PMID- 11819878
TI  - The theory and practice of internal 'tunnel' restorations: a review of the
      literature and observations on clinical performance over eight years in practice.
AB  - The tunnel or 'internal' restoration to restore an approximal caries lesion was
      first described in 1984. The technique allows the operator to conserve the
      important external anatomical features of the tooth, thereby saving considerable
      clinical time while leaving relatively little of the material externalized. The
      development of a new generation of glass-ionomer materials with higher flexural
      and compressive strengths appears to satisfy the main objective of carious
      dentine replacement facilitated by a 'keyhole' internal preparation. The long
      term clinical evaluation of these materials is difficult since new formulations
      are being continually developed. The literature was reviewed. Clinical cases
      restoring approximal caries lesions in permanent molars and premolars were
      observed in a private practice. Over the course of eight years 60 tunnel
      restorations were placed in 48 regularly attending patients. The materials used
      in both total and partial tunnel restorations were Ketac Silver, Hi-Dense and
      Fuji IX. At eight years a failure rate of 15% was seen in the 50 restorations
      observed at last dental examination. The findings suggest that modern tunnel
      techniques may offer a restorative technique worthy of consideration in treating
      primary approximal caries lesions.

PMID- 11819879
TI  - The National Institute of Dental and Craniofacial Research.

PMID- 11819880
TI  - A study to determine the acceptability in patients and dentists of toluidine blue
      in screening for oral cancer.
AB  - Opportunistic screening for oral cancer has been advocated as a possible
      beneficial procedure, especially with high-risk individuals. To assist in the
      identification of malignant lesions a dye has been developed which can be used
      routinely. Issues of acceptability for both patient and practitioner are raised.
      The adoption of this procedure for employees in a large retail chain in the UK
      has enabled an investigation into the use of the dye. The objective of the study
      was to determine the acceptability of toluidine blue in aiding the screening for
      oral cancer in regular attending dental patients who are at high-risk. A two
      stage study design was conducted. The first stage consisted of a patient survey
      in which 10 patients from each of 14 stores of the retail chain were invited to
      complete a questionnaire. The level of embarrassment, taste and anxiety about the
      procedure was assessed. The second stage included a clinician questionnaire and
      telephone interview on the difficulties, if any, of conducting the screening
      procedure with the aid of the dye. The oral health screen (OHS) with OraScreen
      procedure was conducted in the retail store medical room. The participants
      consisted of 140 employees attending the routine dental examination at the store
      of their workplace. All employees in the survey reported that they smoked
      tobacco, drank alcohol and were over the age of 40 years. Fourteen dentists
      visited the stores to complete examinations, screening, questionnaires and
      telephone interview. The main outcome measures consisted of dentist and patient
      rating scales of acceptability developed for the study. Of the respondents 89% (n
      = 124) gave usable questionnaire data. The patients found the dye acceptable (for
      example 83% rated the oral health screen 'a comfortable experience') and 93%
      expected the examiner to give an opinion of the state of their mouths. A wish was
      expressed by 95% to take part in future oral health screens. The dentist
      respondents were in favour of the use of the dye. In conclusion, the
      acceptability of toluidine blue dye to assist in the screening for oral cancer is
      good according to both patient and clinician. The use of this dye should now be
      encouraged more extensively by trained clinicians in the identification of oral
      cancerous and precancerous lesions.

PMID- 11819881
TI  - The value and use of 'quality of life' measures in the primary dental care
      setting.
AB  - General dental practitioners are used to taking a dental history and carrying out
      an examination. The history and examination invariably form the basis of the
      patient-dentist dialogue with regard to the treatment to be provided and the
      financial costs involved. The dialogue between patient and dentist is complex,
      and the importance of 'quality of life' for the patient is now emerging as a
      central focus of this dialogue. This paper explores the concept of 'quality of
      life'. In terms of oral health, and considers the potential of 'oral health
      related quality of life' measures for general dental practice. Examples of their
      use in general dental practice are considered, in relation to marketing dental
      services, improving compliance in treatment plans, assessing the quality of care
      and improving communications between the patient and the dental team. Quality of
      life indicators are being used in the healthcare sector for commissioning,
      planning and evaluating services. In addition, primary care researchers are using
      these indicators as part of their evidence-based treatment approaches. As general
      dental practitioners become more involved in planning services and research, it
      is important they understand the impact of 'quality of life' indicators have on
      their treatment and practice management.

PMID- 11819882
TI  - Cerana--a direct ceramic inlay technique.
AB  - Ceramic materials provide aesthetic restorations which are able to withstand the
      oral environment but two appointments are needed to fabricate ceramic
      restorations by means of an indirect technique. However, single-visit systems are
      becoming available and a recent development, Cerana, utilises matched drills with
      pre-etched and silanated leucite inlays. The cavity is refined using one of three
      conical burs and a size- and shaped-matched conical inlay is cemented using a
      conventional restorative resin material. The final restoration consists of a
      leucite inlay surrounded by a small amount of composite resin. The exposed resin,
      being a restorative composite resin, has a higher filler loading than that of a
      luting cement and an overlap technique can be used to reduce the area of exposed
      surface resin. This paper describes the technique and illustrates some cases. The
      initial results are promising in terms of aesthetics, patient acceptance,
      occlusal wear and ease of use. The major clinical application of this new
      technique is the ability to restore a cavity with a leucite inlay at a single
      visit thereby offering a cost-saving alternative to current aesthetic
      restorations. The technique requires only a little more time than a direct
      placement composite restoration yet reduces polymerisation contraction, and the
      occlusal contacts can be placed on the ceramic surface, rather than on the
      composite resin, for longer-term stability.

PMID- 11819883
TI  - The use of adhesive restorations in the management of localised anterior
      toothwear.
AB  - Toothwear appears to be increasingly common, particularly in the younger age
      groups, and will often require restorative intervention to provide satisfactory
      appearance and function. Well established conventional restorative techniques can
      be relatively complex and time-consuming and as a consequence may not be
      accessible for many patients. This paper, with the help of the literature,
      discusses the alternative application of a variety of adhesive materials and
      techniques used in the restoration of moderate to severe anterior toothwear.

PMID- 11819884
TI  - Rectangular collimation.

PMID- 11819885
TI  - A clinical audit project. Management supervision.
AB  - This paper describes an audit of management supervision of tasks delegated to
      staff, covering general management, such as meeting health and safety
      requirements, and clinical management, such as changing of disinfectant solutions
      according to protocols. The project resulted in the establishment of a series of
      management check-lists which are illustrated.

PMID- 11819886
TI  - MGDS log diary case presentation.
AB  - This case was presented as a log diary for the 1998 diet of the Diploma of
      Membership in General Dental Surgery (MGDS) and describes the history,
      examination, investigation, diagnosis and treatment planning for a 29-year-old
      male who complained about his unaesthetic anterior post-retained crowns and
      occasional pain from his upper right canine. Description of the treatment
      incorporates routine conservation, stabilisation of oral health, anterior space
      creation using a removable cobalt chromium Dahl appliance and the subsequent
      removal of four anterior teeth and their immediate replacement with an acrylic
      resin partial denture. Finally, a porcelain veneer on the upper left central
      incisor and a cobalt chromium partial denture were provided. Continuing care
      includes monitoring an early carious lesion and the position of two unerupted
      wisdom teeth, and regular review of oral hygiene measures.

PMID- 11819887
TI  - SIGN now ... NICE next?

PMID- 11819888
TI  - Is it better to leave or restore carious deciduous molar teeth? A preliminary
      study.
AB  - INTRODUCTION: The objective of this study was to compare the extraction and
      exfoliation experience of filled and unfilled carious deciduous molar teeth.
      METHOD: The study was carried out in 1997 in four general dental practices in
      south Cheshire, UK and involved a longitudinal retrospective review of case
      notes. A quota sample of 20 case notes of children from each practice was
      selected according to strict criteria. Subjects had to: Have had experience of
      approximal caries in one or more of the deciduous molar teeth. Have a date of
      birth between 1st January 1984 and 31st December 1985. Be a regular attender and
      in continuous contact with the practice. Data were collected on a common data
      abstraction form. Variables measured included: Base-line dmft. Site and number of
      filled teeth. Site and number of unfilled carious teeth. Number of courses of
      antibiotics. Site and number of pulp therapies. Site, number, method (local or
      general anaesthetic) of extractions. Reasons for extraction. All teeth not
      recorded as being extracted were assumed to have exfoliated. In addition,
      information was collected on the dentists' treatment philosophies. A series of
      group discussions revealed that the four dentists fitted into two groups
      according to treatment philosophies; two dentists shared a philosophy of minimal
      intervention, the other two shared the same views of treating more radically.
      RESULTS: There was no significant difference between the proportion of filled
      teeth and the proportion of carious unfilled teeth that were extracted (chi
      square 0.05 P = 0.83). A logistic regression showed that for each course of
      antibiotics administered the odds of having an extraction was multiplied by 5.5
      and children who were patients of the interventionist dentists were five times
      more likely to have an extraction than patients of non-interventionist dentists.
      CONCLUSION: Although the study was preliminary in nature no clear benefit could
      be found in filling deciduous molar teeth against leaving carious teeth unfilled,
      if avoidance of extraction was the desired outcome. The treatment philosophy of
      dentists was a major factor in determining extraction or exfoliation outcomes.
      This issue is complex with many interacting factors to be accounted for and will
      require multiple well-designed studies to provide an answer.

PMID- 11819889
TI  - Increased lower denture security using the Myoloc system.
AB  - PURPOSE OF THE STUDY: To assess whether the Myoloc System. Improves the stability
      of the mandibular complete denture. METHOD: Unstable dentures move during
      function causing pain and discomfort to patients resulting in decreased denture
      security. Improvement in patients' perceived denture security was used to assess
      if the Myoloc System improved the stability of the mandibular complete denture.
      Complete dentures were constructed for 27 patients (20 female and seven male) by
      conventional methods. Patients were asked to mark a point on a visual analogue
      scale to indicate their denture security. Following this, copies of the
      mandibular dentures were made and Myoloc wings added to the dentures. Denture
      security was recorded once again. The two responses were statistically analysed
      for significant improvement. RESULT: A statistically significant improvement in
      denture security was found to occur after addition of the Myoloc wings to the
      mandibular denture. CONCLUSION: The Myoloc System improves the stability of the
      mandibular complete denture and may prove useful when conventional methods fail
      to provide adequate denture stability and the patient is not a candidate for
      surgery.

PMID- 11819890
TI  - Appropriate and inappropriate referrals to a unit of conservative dentistry.
AB  - Inappropriate referrals to secondary care are an unnecessary cost,
      notwithstanding the effect on waiting lists. It is essential therefore that only
      those patients whose referrals are appropriate are actually referred for
      secondary care. This project aimed to determine whether referrals to a unit of
      conservative dentistry are appropriate. The records of 120 consecutive new
      patient referrals who had been examined by one consultant in the unit of
      conservative dentistry at Glasgow Dental Hospital and School were obtained. A pro
      forma was designed on which synopses of the relevant clinical findings were
      written. These synopses were examined by four general dental practitioners
      (GDPs). A referral was considered appropriate if three or four of the GDPs
      considered it to be so, a referral was considered inappropriate if three or four
      of the GDPs concurred. Of the 120 cases examined, a majority of the GDP assessors
      agreed that 54 warranted referral, with 23 of these being referrals for
      toothwear. Agreement was not reached in 35 cases, while 31 referrals were
      considered inappropriate. Of the 31 cases which were considered inappropriate, 27
      were thought to be within the scope of general practitioners. In conclusion, the
      results suggest that around one quarter of referrals to a unit of conservative
      dentistry are inappropriate. It would appear that a number of GDPs are unable or
      unwilling to treat a variety of simple conditions in practice and it may be that
      the development of referral guidelines is necessary to ensure that only those
      patients who merit a specialist opinion are referred for this service.

PMID- 11819891
TI  - Hoarseness: a potential role for the dentist in early diagnosis.
AB  - A patient who smoked heavily was under regular review by the oral medicine
      department because of oral keratosis. He subsequently complained of hoarseness of
      the voice, and was referred to the department of otorhinolaryngology. An early
      squamous cell carcinoma of the larynx was diagnosed, and the patient was treated
      with radical radiotherapy. This case highlights the importance of early diagnosis
      and the potential role of the dentist in the total healthcare of patients.

PMID- 11819892
TI  - A survey of patient perceptions of dental charges.
AB  - The aim of this study was to examine patients' perceptions of charges for dental
      treatment. A sample of 96 patients attending the University Dental Hospital of
      Manchester completed two short questionnaires on the monetary value of various
      dental treatments (a dental examination, a scaling, an amalgam restoration, a
      crown, an extraction, a denture, a root filling and a radiograph). The first
      questionnaire gave no details of the procedures and also asked patients which of
      the items of treatment they had experienced. The second questionnaire asked about
      the monetary value of the same items but gave the patients a short description of
      what the procedure entailed. The mean values for all the items of treatment were
      significantly higher in the second questionnaire than in the first. Patients who
      had a crown placed a significantly higher value on this treatment than patients
      who did not have a crown. The implications for pricing strategies in general
      dental practice are discussed.

PMID- 11819893
TI  - Who uses independent dental services? Findings from a national survey.
AB  - This study was designed to determine private dental services use in the UK and to
      determine if those who use an independent dental service attend more regularly,
      in addition to identifying factors associated with the use of private dental
      care. A random probability sample of 2668 addresses was selected from the British
      Postcode Address File (PAF) and 1865 adults aged 16 years or older took part in
      this study (70%). Respondents were interviewed in their homes about their use of
      dental services and socio-demographic information was collected. The data were
      analysed using the statistical package CHAID. A total of 23% (424) reported to be
      seen on a private basis the last time they visited the dentist. Of those, 54%
      (230) reported to have attended the dentist within the last six months compared
      to 46% (629) of those who used NHS services (P < 0.05). Level of income was
      identified as the most significant factor in determining the use of private
      services, this being greater for those earning above 30,000 Pounds (P < 0.05).
      For those on low (< 10,000 Pounds) or middle (10,000 Pounds-< 30,000 Pounds)
      incomes, area of residence was the next most important factor in determining
      private service use. Residents of London and the South East in both low- and
      middle-income groups were more likely to use private services (P < 0.05).
      Residents of the North of England and the Midlands/East Anglia were less likely
      to use private services (P < 0.05). In conclusion, income and area of residence
      appear to be the most important determining factors in the use of private dental
      services.

PMID- 11819894
TI  - "Painless" insurance checkup.

PMID- 11819895
TI  - An interview with Dr. Gary Blanchette, 1999-2000 LDA President. Interview by
      Edward P. Roberson.

PMID- 11819896
TI  - The fascination of understanding oral cancer through basic science research.

PMID- 11819897
TI  - Clinical application of basic research in oral cancer.

PMID- 11819898
TI  - Oral complications of cancer patients.

PMID- 11819899
TI  - The Division of Oral and Maxillofacial Surgery at Columbia Presbyterian Medical
      Center--a.k.a. HSDM South.

PMID- 11819900
TI  - An update on the management for the dental patient with Sjogren's syndrome and
      xerostomia.
AB  - Sjogren's syndrome is a chronic and uncomfortable inflammatory condition for the
      individuals who suffer from it. There are many and varied systemic and oral
      complications associated with Sjogren's syndrome. It is also a complex and
      challenging condition for the dentist to diagnose and manage. The key concepts
      are early recognition and intervention to prevent the secondary complications
      from hyposalivation. To the degree possible, salivary flow should be restored by
      either artificial salivas or stimulated by secretogogues or both, which is
      usually the case. Atrophy and secondary infections of the oral mucosa should be
      properly identified, effectively treated, and frequently monitored. Pilocarpine
      HCl (Salagen) has been shown to be effective in increasing salivary flow in
      patients with SS. Preventive and supportive therapy including supplemental
      fluorides, dietary assessment, and frequent professional recalls are imperative
      to maintaining the oral health of the patient with SS.

PMID- 11819901
TI  - Sjogren's syndrome: an educational roundtable.

PMID- 11819902
TI  - The view from the tip of the iceberg: taking the University of Minnesota School
      of Dentistry into the twenty-first century.

PMID- 11819903
TI  - Reaching out ... a dental school initiative.

PMID- 11819904
TI  - Buffalo Commons for dentistry as well?

PMID- 11819905
TI  - Fluoridation and Medicaid costs in Louisiana.

PMID- 11819906
TI  - De-mystifying the LSBD inspection.

PMID- 11819907
TI  - Democracy 101 and the ADA--It's not just about managed care.

PMID- 11819908
TI  - [Inflammation and acute otitis media].
AB  - 1. EPITHELIUM OF THE MIDDLE EAR: The middle ear has a respiratory type
      epithelium. The mucus is produced by mucosal and by submucosal cells in the
      Eustachian tube. 2. LYMPHOID TISSUE: The defensive barrier of the mucosa is
      potentialized by lymphoid tissue in the middle ear that produces a local specific
      immune response. Bacterial and viral antigens can induce an inflammatory
      reaction. 3. TUBOTYMAPNIC CAVITIES: The humoral immune system (B lymphocytes)
      secreting IgG, IgA and IgM) and cell mediated response (T lymphocytes) are active
      in the tubotympanic cavities. 4. MAST CELLS: Present in contact with vessels and
      nervous fibers of the tubotympanic chorion, mast cells are activated by IgE
      linkage to antigens, leading to local allergic inflammatory phenomena with
      production of histamine, C leukotrienes, platelet activating factor (PAF) and
      cytokines. 5. MAINTAINING OPEN CAVITIES: During the inflammatory reaction, mucus
      secreting cells are stimulated and their glycoprotein secretions are modified.
      Since the middle ear epithelium has a water-absorption action contributing to
      aeration of the middle ear cavities. 6. CYTOKINE RESPONSE: During acute middle
      ear otitis, cytokines secreted in response to bacterial and viral
      lipopolysaccharides include tumor necrosis factor alpha (TNFa) which plays a
      crucial role: induction of fibroblast proliferation, activation of
      polymorphonuclears, inhibition of vascular endothelial tissue and B lymphocytes.
      It facilitates healing of the middle ear infection, but an also induced
      pathological lesions in case of incomplete repair. 7. BACTERIAL FLORA:
      Haemophilus influence, Branhamella catarrhalis, and Streptococcus pneumoniae
      colonize the respiratory epithelium of the middle ear via the Eustachian tube,
      generally after viral infection. 8. GLUCOCORTICOIDS: Administered before
      injection of a bacterial endotoxin, glucocorticoids significantly reduce
      inflammatory phenomena in acute otitis induced in rat models. In acute middle ear
      models in the guinea pig, corticosteroids reduce lipoperoxidation; free radicals
      are the cause of the persistence of inflammation in the acute middle ear. 9.
      NEUTROPHIL MIGRATION: Antibodies blocking cell adhesion molecules (CAM), or
      instance antiCD11 B and antiCT 18, inhibit polymorphonuclear migration, and could
      be very useful for the treatment of acute middle ear infection. Use of
      prostaglandin inhibitors does not significantly reduce the risk of residual
      effusion at 10 and 30 days after the acute episode. 10. CLINICAL TRIALS: There is
      a significant body of scientific evidence proving the efficacy of combining
      antiinflammatory drugs and antibiotics for first line treatment of middle ear
      infection to prevent seromucosal otitis.

PMID- 11819909
TI  - [Inflammation and seromucous otitis].
AB  - 1. AN IMPORTANT RELATIONSHIP: There is a strong relationship between tubular
      dysfunction, tympanic depression and effusion of the tympanic cavity. 2. TWO
      IMPORTANT PHENOMENA: Increased secretory capacity of the mucosa and decreased
      mucociliary clearance subsequent to a reduction in the number of ciliated cells
      have an important impact. 3. CONTINUUM: Rhinopharyngeal infection, acute middle
      ear infection and seromucosal otitis constitutes a continuum demonstrated by the
      fact that PCR (polymerase chain reaction) studies reveal the same germs in the
      rhinopharynx, in the middle ear fluid, and in seromucous otitis (SMO) effusions.
      4. BACTERIA AND VIRUSES: By producing toxin, bacteria and viruses induce severe
      inflammatory reactions in SMO, triggering the cascaded of inflammation mediators.
      5. MEDIATORS: Several elements participating in the cascade of inflammatory
      events have been demonstrated in human patients and animal models of SMO despite
      the minimal number of elements producing inflammation mediators initially.
      Recurrent favoring factors have a primordial effect. 6. ALLERGY: The clinical and
      epidemiologic data are widely debated, but do not favor the hypothesis of an
      allergic reaction, yet several studies have demonstrated that mediators of the
      allergic response are present in SMO effusions. 7. ANTIBIOTICS: Used in short
      term regimens, antibiotics have a favorable [not readable: see text] on SMO, but
      their duration of action is short due to the persistent inflammatory reactions.
      8. ORAL CORTICOSTEROIDS: The beneficial effect of oral corticosteroids in SMO is
      generally short-lived with a rapid decline in efficacy after a few weeks. 9. LONG
      DURATION AND RELAPSE: SMO is usually a long-standing highly recurrent condition
      proscribing use of long-term systemic corticosteroids. It might be interesting to
      assess the contribution of local corticosteroid therapy after classical "acute"
      treatment associating antibiotics and a short course of oral corticosteroids. 10.
      OTHER OPTIONS: Clinical trials using other treatment options in SMO have not been
      conclusive for mucolytic, decongestant or antihistamine agents.

PMID- 11819910
TI  - [Inflammatory acute rhinosinusitis].
AB  - 1. COMMON COLD: A rhinovirus, the causal agent usually found in common cold,
      stimulates the local abundance of polymorphonuclears resulting from IL8
      secretion. Enzymes and free radicals released by these polymorphonuclears explain
      the subsequent inflammation. 2. TREATMENT: Treatment for viral rhinosinusitis in
      adults is based on vasoconstrictors, often associated with anti-histamine agents
      with atropinergic action. The possible contribution of pure atropinergic agents
      is currently under evaluation. Non-steroidal antiinflammatory drugs (NSAID)
      appear to have no effect and corticosteroids are not indicated. 3.
      RHINOSINUSOPHARYNGITIS IN CHILDREN: These childhood diseases, which after
      adaptation disappear spontaneously around the age of 7 to 8 years, result from
      viruses, distinct from those observed in adults, which have a more pronounced
      cytolytic and general effect. Proposed treatments are designed to lower the
      temperature using physical (warm bath, abundant fluids) and medicinal means.
      Paracetamol is preferred over aspirin because it has less side effects. NSAID
      have not been found to provide any efficacy. Decongestants are an ideal
      indication but their use is limited by age. Antibiotics are not warranted, at
      least for the non-complicated forms. Familial education is indispensable for
      proper management without antibiotics. 4. ACUTE BACTERIAL RHINOSINUSITIS:
      Originating from the relatively constant microbial flora in the nasal cavities,
      acute bacterial rhinosinusitis in France is basically caused by Haemophilus
      influenzae, beta hemolytic Streptococcus, Streptococcus pneumoniae,
      Staphylococcus aureus, and Branhamella catarrhalis. The proportion of Gram
      negative germs appears to depend on age and rate of recurrence. There is debate
      about the impact of viral-bacterial interactions; no definite conclusions can be
      drawn from current knowledge. 5. BACTERIAL INFLAMMATION IN ACUTE RHINOSINUSITIS:
      Antibiotic therapy is the first intention treatment for bacterial inflammation
      caused by acute rhinosinusitis. In case of failure, surgery (puncture or
      microsurgery as needed) may be indicated. 6. NSAID IN BACTERIAL RHINOSINUSITIS:
      The contribution of NSAID would be limited due to the unfavorable efficacy
      adverse effect ratio. Short courses of corticosteroids are commonly used. Two
      studies conducted with well-designed methodology, have recently proven the
      efficacy of coticosteroids in reducing the duration and intensity of spontaneous
      pain in acute maxillary rhinosinusitis in adults. One of these studies
      demonstrated a reduction in nasal obstruction. These studies confirm the absence
      of any notable adverse effect in comparison with placebo. 7. ACUTE RHINOSINUSITIS
      CAUSED BY DENTAL PROBLEMS: Due to the anatomic disposition (sinusal teeth), the
      rhinosinusitis is generally unilateral, resulting from paradontal or apical
      infection. Such cases are exceptional (5% to 10% of all cases of acute
      sinusitis). 8. CONTAMINATING FLORA IN ACUTE RHINOSINUSITIS: Anaerobic and
      microaerophilic germs predominate, generally coming from the buccal floral or the
      edodontoid or periodontoid flora. 9. SURGICAL TREATMENT: Associated with dental
      care, sinus puncture or meatomy may be required for evacuation of the sinus.
      Antibiotics directed against a wide variety of aerobic germs (amoxicillin
      clavulanic acid or pristinamycin are generally recommended) should be given
      before and after surgery. The role of NSAID is evaluated in terms of the benefit
      (pain relief)/adverse effect ratio, which in the present situation can be
      considered to favor the antalgesic action during or before dental care. 10. THE
      QUESTION OF SHORT COURSES OF CORTICOSTEROIDS: The contribution of short courses
      of corticosteroids is assessed in the same manner as for maxillary sinusitis
      resulting from the nasal flora.

PMID- 11819911
TI  - [Allergic rhinitis].
AB  - 1. ALLERGY: The prevalence of allergy is estimated from 15 to 35%, incidence is
      on the rise. 2. PATHOGENESIS: Allergy is initiated by a very specific IgE
      dependent mechanism, but involves a late phase corresponding to non-specific
      inflammation. 3. SYMPTOMATIC CARE: "Modern" antihistamines and local intranasal
      corticosteroid therapy constitute the basis of symptomatic treatment.

PMID- 11819912
TI  - [Nasal-paranasal sinus polyposis].
AB  - 1. POLYPOSIS AND ALLERGY: Nasosinusal polyposis and allergy must be considered as
      two distinct conditions. 2. POLYPOSIS: Approximately 1% of the general population
      has nasosinusal polyposis, a condition strongly associated with asthma (about one
      third of the patients with polyposis have asthma). Patients with nasosinusal
      should undergo a complete respiratory examination in order to search for asthma
      or an asthma equivalent. 3. EOSINOPHILS: Eosiophils play a crucial role in the
      inflammatory reaction, releasing almost all the known inflammatory mediators:
      cytokines, chemokines and growth factors. 4. EPITHELIAL CELL: The epithelial cell
      probably plays a very important role. 5. MEDICAL TREATMENT: Long-duration
      intranasal corticotherapy is the basis of drug treatment. Short courses of oral
      corticosteroids may be useful during acute episodes in inflammation. The exact
      effect of oral corticosterid is not clearly elucidated but it is known that non
      steroidal antiinflammatory drugs (NSAID) are contraindicated in polyposis. 6.
      SURGICAL TREATMENT: Surgery is reserved for medical failures or for patients with
      a contraindication for drug therapy. Endonasal ethmoidectomy is the basis
      treatment. 7. PERSPECTIVES: Better understanding of the underlying
      pathophysiology and the probable genetic component will determine future
      treatments. Perspectives include antiinflammatory drugs currently reserved for
      other conditions (antileucotriene, antiTNFa, IL-18) and elaboration of new
      antiinflammatory drugs.

PMID- 11819913
TI  - [Inflammation and laryngitis].
AB  - 1. DISTINCT ENTITIES: Unlike inflammation or the middle ear or nasal or sinus
      cavities, there is no direct link between acute and chronic inflammation of the
      larynx. Chronic laryngitis is a distinct nosological entity. Patients with
      recurrent allergic laryngitis do not necessarily develop chronic laryngitis as is
      observed in patients with nasal allergy. 2. RESEARCH: There is no research data
      on infections of the larynx comparable to that available for the middle ear or
      the nasal cavities. This is probably related to the difficulty of accessing the
      laryngeal mucosa and the risks related with this condition. 3. CLINICAL TRIALS:
      While fundamental research remains to be conducted, their is a large body of
      clinical trials on the topic, although one must be prudent concerning the terms
      used. 4. NOSOLOGOGY: In French the term "croup" designates diphtheritic croup and
      must be distinguished from the more general term used in English. Clinical trials
      must be interpreted with caution since it is often difficult to ascertain which
      type of laryngitis is concerned. 5. GRAVITY SCORES: Widely used in the English
      literature, gravity scores are not generally used in French pediatric ENT units
      and have no real equivalent in French. 6. DYSPHONIA AND DYSPNEA: Dysphonia is the
      leading sign of chronic laryngitis. Dyspnea is the leading sign of acute
      laryngitis. Dyspnea is more frequent in children and is related to disease
      severity. 7. BACTERIA AND VIRUSES: Epiglottitis (supraglottic laryngitis) is
      related to bacterial infections while subglottic laryngitis is related to viral
      infections requiring antibiotics in combination with corticosteroids. 8. H.
      INFLUENZAE: The most common causal agent of epiglottitis, type B Haemophilus
      influenzae, is not the only culprit. 9. ADULTS: Epiglottitis can also occur in
      adults where it is as severe as in children. 10. SYSTEMIC CORTICOSTEROIDS:
      Emergency administration of systemic and inhaled glucocorticoids in the hospital
      setting is the basic treatment for glotto-subglottic laryngitis. Dosage must be
      high, more than 0.3 mg/kg dexamethasone for 48 hours, followed by oral
      corticosteroids.

PMID- 11819914
TI  - [Inflammation and acute pharyngo-tonsillitis].
AB  - 1. FACTS: Despite several studies, it has been impossible to establish a
      correlation between bacteriological and clinical findings in erythematous
      pultaceous sore throat. 2. A RULE: Antibiotics should be prescribed for group A
      streptococcal sore throat alone. 3. INFLAMMATION AND INFECTION: In acute
      tonsilitis, inflammation is perfectly proportional to infection; 4. INFLAMMATORY
      CYTOKINES: Their extremely important role in the pathogenesis of different
      inflammatory processes has been demonstrated in acute tonsilitis. 5.
      RECOMMENDATION: Based on the fact that no clinical argument can confirm or infirm
      the streptococcal cause, it is recommended to use a rapid diagnostic test in all
      adults or children with sore throat. 6. A QUESTION: No data are available
      demonstrating the benefit of non-steroidal antiinflammatory drugs at
      antiinflammatory doses or of general corticosteroid treatment of acute sore
      throat. Nevertheless, in non-A hemolytic streptococcal where antibiotic treatment
      is not indicated, wouldn't it be useful to prescribe symptomatic antiinflammatory
      treatment?

PMID- 11819915
TI  - [Pharmacology of glucocorticoids and ENT pathology].
AB  - 1. NATURAL AND SYNTHETIC HORMONES: Glucocorticoids are indispensable circulating
      hormones implicated in carbohydrate and protein metabolism. They also have strong
      antiinflammatory effects used in therapy. This antiinflammatory activity has led
      to the development of synthetic compounds with an antiinflammatory action that is
      much greater than that of the natural hormones (cortisol, cortisone) with reduced
      mineralocorticoid activity. 2. ANTIINFLAMMATORY EFFICACY OF GLUCOCORTICOIDS: The
      action of glucocorticoids on the majority of the cells involved in inflammatory
      reactions, particularly in allergy, and their induction of synthesis of new
      inflammation mediators explains their antiinflammatory effect. 3. MECHANISMS OF
      ACTION: The antiinflammatory properties of glucocorticoids result basically from
      their inhibitory effect on synthesis of proinflammatory proteins, in particular
      many cytokines. Corticoids reduce the production of prostanoids by inhibiting the
      expression of COX-2, but are much less effective on the production of
      leukotrienes. Corticoids inhibit the degranulation of human basophils (histamine
      release) but have no effect on mast cells. 4. ACTIVATION OF A CYTOPLASMIC
      RECEPTOR: The antiinflammatory effect of glucocorticoids is mediated by binding
      to a cytoplasmic receptor which, when activated, migrates to the nucleus. The
      activated receptor can interact with transcription factors (NF-kappa B, AP-1)
      inhibiting the synthesis of proinflammatory proteins (cytokines, COX-2...). This
      "transrepressive" activity explains most of the antiinflammatory effects of
      glucocorticoids. 5. ACTION OF THE ACTIVATED RECEPTOR: The activated receptor can
      bind to specific sites present on the regulator region of target genes, inducing
      their transcription (or transactivation). This induction effect on protein
      synthesis concerns the renin-angiotensin system, neoglucogenesis, and bone
      metabolism. Increased production of these proteins explain the metabolic and
      endocrine effects of glucocorticoids which, when exaggerated, particularly with
      general administration, can lead to undesirable effects. At the present time, our
      knowledge suggests it would be best to have molecules with a predominant
      transrepressive activity (antiinflammatory activity) since the transactivator
      effects appeared to be associated with the undesirable metabolic effects of
      glucocorticoids. 6. OTHER PHARMACEUTICAL PROPERTIES: Glucocorticoids also have
      properties that do not require gene expression. These "non-genomic" effects could
      occur at high dosage "pulse" therapy. We will have to wait for more pertinent
      clinical information on these effects to use the power of these non-genomic
      effects to guide our choice of the appropriate glucocorticoid in given clinical
      situations. 7. LOCAL TREATMENT FOR ALLERGIC RHINITIS: Given locally
      glucocorticoids reduce the concentration of many inflammatory mediators and the
      number of inflammatory cells in secretions and nasal biopsies. The efficacy of
      glucocorticoids is perfectly established in this indication as well as in nasal
      polyposis. 8. LOCAL TOLERANCE: During the first days of treatment, local
      application of corticoids on the inflammatory mucosal surface can cause
      irritation and/or sneezing. These manifestations generally subside in a few days
      and are more frequent with solutions containing glycol. The dry nose sensation,
      sometimes associated with minimal epistaxis, is classically reported, though at a
      low frequency. A few rare cases of ulceration of perforation of the septum have
      been report and it would be difficult to exclude a mechanical cause related to
      administration route. It is clear that the risk of mucosal atrophy has been
      eliminated with the use of nasal corticosteroids. 9. EVALUATION OF THE SYSTEMIC
      EFFECT OF NASAL CORTICOSTEROIDS: Most of the studies have examined the
      hypothalamo-pituitary-adrenal axis. These studies have rarely demonstrated, an
      then in isolated cases, any significant modification at recommended doses.
      Likewise for other markers of passage into the systemic circulation such as
      osteocalcine or the number of circulating eosinophils. There is also very little
      risk of growth impairment in children or cataracts in adults. 10. SHORT-COURSE
      GENERAL CORTICOSTEROID THERAPY: Short periods are sometimes recommended for
      rhinitis, sinusitis, polyposis or laryngitis. Use of a short duration treatment
      (about one week) at doses in the 1 mg/kg/d range, induce a transient inhibition
      of the corticoadrenal axis in about half the patients; this inhibition disappears
      in most all cases in two weeks. The clinical risk associated with this alteration
      in patients under stress (infection, trauma...) remains hypothetical. In any
      case, it would be advisable to avoid repeating short-course general
      corticosteroid therapy at close intervals.

PMID- 11819916
TI  - [Pharmacology of non-steroidal anti-inflammatory drugs and ENT pathology].
AB  - 1. BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAID) belong to a variety
      of chemical classes with no common features except the absence of a steroid
      structure. Their primary effect is pain relief, but also with anti-pyretic and
      anti-inflammatory effects. Basically prescribed for symptomatic relief, they do
      not have a curative effect on chronic disease processes. 2. INFLAMMATORY EFFECTS
      OF PROSTANOIDS (THROMBOXANE A2 AND PROSTAGLANDINS): Inflammation basically
      results from the pro-algogenic and vascular effects of prostanoids. Their pro
      algogenic effects are explained by sensitization of nociceptive nerve endings to
      the stimulating effect (algogenic) of kinins (bradykinin), serotonin and
      histamine. In addition, production of prostanoids in the brain has a
      thermoregulatory effect. 3. MODE OF ACTION: NSAID have a common effect,
      inhibiting the production of prostanoids via reduced activity of two cyclo
      oxygenases (COX-1 and COX-2). COX-2 is an isoform predominantly expressed during
      the inflammatory process. Excepting two compounds recently marketed (celecoxib,
      rofecoxib) selective for COX-2, all other NSAID have few or no selective
      properties. COX-1 is implicated in the regulation of many physiological
      functions. Inhibition of COX-1 explains most of the classical side effects of non
      selective NSAID. 4. COMPARISON: It is classical to emphasize the interindividual
      variable anti-inflammatory and antalgesic effects of the different NSAID without
      developing a coherent explanation. In addition, it is very difficult to make
      objective comparisons between different NSAID because of the different sizes of
      the study populations, indications and dosages. There is no evidence favoring a
      given NSAID on the basis of its anti-inflammatory or antalgesic effect in a given
      indication; no hierarchy in terms of efficacy can be established. For acute pain,
      it is preferable to use oral NSAID absorbed rapidly to achieve rapid relief. 5.
      PARACETAMOL: This antalgesic, antipyretic drug has no anti-inflammatory action.
      Its mechanism of action remains to be fully elucidated. It is not a member of the
      NSAID class and is a poor inhibitor of COX, particularly COX-2 (30% maximal
      inhibition). For identical dose (1-3 g/d), the antalgesic activity of paracetamol
      is comparable to that of aspirin for pain in general. There does not appear to be
      any difference in the anti-pyretic efficacy between NSAID and paracetamol. 6.
      OFFICIAL INDICATIONS: In general, NSAID are not indicated for anti-inflammatory
      action in the ENT conditions discussed here. It this light, the official
      indications in France published on November 14, 1988 concerning ENT disease in
      children and adults without risk factors is most noteworthy. It is stipulated
      that there is no need to institute NSAID treatment at an anti-inflammatory dose
      in combination with general antibiotic therapy, except when there is an important
      inflammatory component. This guideline does not concern NSAID at antalgesic and
      antipyretic doses used for ENT conditions with or without an infectious
      component. 7. SELECTIVE INHIBITORS OF COX-2: Selective inhibitors are only
      indicated in two chronic inflammatory diseases: osteoarthritis and rheumatoid
      arthritis. There is no indication for these inhibitors in ENT disease. The only
      beneficial effect that has been demonstrated to date for the use of selective
      inhibitors of COX-2 is better digestive tract tolerance. 8. ROLE OF PROSTANOIDS
      IN THE CLINICAL EXPRESSION OF ALLERGIC RHINITIS: It is insufficient to warrant
      use of NSAID in this disease, particularly due to the efficacy of anti-H1 and
      local corticosteroids. NSAID are not indicated in nasal polyposis and are even
      contraindicated in case of intolerance to NSAID, observed in about 15-20% of all
      patients with nasal polyposis. However, local application of lysine
      acetylsalicylate at progressive doses from 20 micrograms to 4 mg can reduce
      relapse by half after polypectomy. There is no proof of the efficacy of NSAID in
      chronic sinusitis and their efficacy has not been studied in laryngitis. Finally,
      there is no sufficient evidence, either from experimental data or clinical
      trials, to recommend NSAID for otitis, with the exception for an antalgesic
      and/or antipyretic effect. 9. CHOOSING AN ANTI-INFLAMMATORY OR ANTALGESIC NSAID:
      The choice is generally guided by the frequency and severity of undesirable
      effects. These undesirable effects often appear during the first weeks of
      treatment. 10. DIFFERENT ADVERSE EFFECTS: Digestive tract effects appear in 20 to
      40% of the patients after a few weeks of treatment using anti-inflammatory doses.
      Symptomatic gastroduodenal ulcers, digestive bleeding, and perforations are the
      most serious adverse effects of NSAID. Nevertheless, the risk of such
      complications, compared with the number of prescriptions, is very low. At high
      dose (anti-inflammatory dose), age over 60 years and history of severe
      gastrointestinal complications are factors increasing the risk of severe
      gastrointestinal adverse effects of NSAID. Minor adverse effects, and more
      importantly severe adverse effects, are significantly reduced with selective COX
      2 inhibitors compared with classical NSAID. It is important to note that these
      beneficial effects in terms of tolerance are not better than with NSAID
      treatments except for treatments at anti-inflammatory doses for more than one
      week. Selective COX-2 inhibitors would have the same adverse effect on the kidney
      as classical NSAID, as pointed out by the precautions for use published by the
      manufacturers. COX-2 is not expressed by platelets. Specific inhibitors do not
      inhibit platelet aggregation and do not lengthen bleeding time. Specific
      inhibitors, like classical NSAID, are not recommended for women desiring
      pregnancy, especially because the risk of a teratogenic effect has not been
      excluded. Conversely, for patients with asthma triggered by classical NSAID,
      selective COX-2 inhibitors do not trigger acute asthma. Finally, selective COX-2
      inhibitors are not currently indicated for children and not for ENT disease.

PMID- 11819917
TI  - [Physiopathologic bases of ENT inflammation].
AB  - 1. ROLE OF INFLAMMATION: Among the phenomena occurring in the organism in
      response to exogenous or endogenous aggression, inflammation is generally a
      beneficial reaction. It can however be deleterious because of its localization or
      its deregulating effect. 2. DIFFERENT PHASES OF THE INFLAMMATORY REACTION: The
      inflammatory reaction occurs in three phases. The first is vasculoexudation:
      dilatation of the blood vessels, followed by plasma exudation and leukocyte
      diapedesis. The second is a cellular or productive phase with formation of an
      inflammatory granuloma. Repair is the third phase, with retraction of the
      inflammatory focus, development of neocapillaries, regeneration of connective
      tissue, and variable regeneration of epithelial tissue. 3. DIFFERENT TYPES OF
      INFLAMMATION: In acute inflammatory processes, vasculoexudation predominates
      while in subacute inflammation, cellular phenomena play the major role. When the
      inflammation becomes chronic fibrosis is the most important process. 4. CELLULAR
      INVOLVEMENT IN INFLAMMATION: Antigen-presenting cells have a most important role.
      T-cells mediate cellular immunity and B-cells hormonal immunity. Monocyte
      macrophages as well as polymorphonuclears support the phagocyte activity. Most
      cells share several functions with basophil polynuclears involved in allergic
      disease as well as in certain non-allergic inflammatory reactions. Endothelial
      cells secrete mediators leading to serum extravasation and influx of inflammatory
      substances and cells. Structural cells and platelets are also involved. 5.
      MEDIATORS OF INFLAMMATION: All cells participating in the inflammatory reaction
      secrete cytotoxic and/or effector and amplifying substances mediating the immune
      response. Soluble mediators include cytokines, acute phase proteins, enzymes,
      plasma activation systems (contact system, complement system, coagulation
      factors, fibrinolysis factors), arachidonic acid metabolites, biogenic or
      vasoactive amines (histamine, serotonin), eosinophil granular proteins,
      neuropeptides, oxygen free radicals, and nitrogen monoxide. 6. BY ETIOLOGICAL
      AGENT: Several varieties of inflammation can be distinguished: foreign body
      reactions, anti-infectious agent reactions, and immunoallergic reactions.

PMID- 11819918
TI  - [Medical treatment of hemorrhaging ulcer].

PMID- 11819919
TI  - [Diagnosis of aspergillosis and other invasive filamentous fungal infections in
      hematology].
AB  - OBJECTIVE: Invasive filamentous fungal infections (FFI) are difficult to diagnose
      in the department of hematology; a variety of arguments are necessary to confirm
      the fungal origin. Our study evaluated prospectively, in a large population in
      South Eastern France, the diagnostic techniques used ante and post mortem
      (mycology, anatomopathology, serology and aspergillosis antigens) to prove an
      FFI. METHODS: Two hundred and twenty eight neutropenic patients with obvious,
      probable, highly probable or presumed FFI were selected. Since completion of this
      study, a new classification of aspergillosis, with 3 instead of 4 levels of
      diagnosis, has been defined by the ICAAC in San Francisco but has not yet been
      published. Mycological or histological examinations were been performed on
      broncho-alveolar washings (BAW), puncture liquids or biopsies. Serology used
      precipitation, hemagglutination, immunofluorescence or ELISA techniques.
      Aspergillosis antigens were researched using the Pastorex method (agglutination
      of latex particles), launched at the beginning of the study. RESULTS: Invasive
      aspergillosis was diagnosed in 43.4% of patients, a non-aspergilla FFI in 6.5%,
      and no fungi was isolated in the cultures of 50% of patients. Ante mortem, 160
      patients underwent BAW with a total of 175 samples. Among the latter, 41.7%
      mycological examinations were positive (presence of mycelium filaments and/or
      positive cultures) with 68.7% of Aspergillus fumigatus. Of the 48 puncture
      liquids, 25% of direct examinations and 29% of cultures were positive. Biopsies
      were taken from 59 patients and explored for mycology: 63.8% of direct
      examinations and 46.8% of cultures were positive; for those explored
      histologically, 76.7% revealed the presence of mycelium filaments. Post mortem,
      17 patients out of 79 deceased underwent a total of 24 autopsy or biologic
      sampling. For 5 patients, FFI was diagnosed post mortem. Aspergillus serology and
      antigen explorations were conducted respectively in 202 and 182 patients and were
      positive in 31% and 33%. The presence of antibodies appears to be a good
      prognostic factor compared with the presence of antigens. CONCLUSION: Biological
      diagnosis of FFI relies on the multiplicity of examinations and renewal of
      mycological sampling.

PMID- 11819920
TI  - [Severe bladder dysfunction in the child abuse victim. Hinman syndrome].
AB  - Severe bladder dysfunction with possible consequence on the upper urinary tract
      caused by psychological trauma were recently identified. Hinman in 1973 was the
      first to report a series of 14 patients with severe abnormal bladder and bowels
      behaviour with organic cause. He described the most common symptoms met in this
      group of patients and their management using a non surgical approach based on
      bladder reeducation and hypnosis. Other authors such as Allen in 1977 reported a
      similar experience and found severe detrusor-sphincter dyssynergia. In 1995,
      Ellsworth reported a relation between these abnormal bladder behaviour and a
      medical history of sexual aggression. We report here in a series of 7 patients
      with Hinman syndrome associated with aggression. Diagnosis and management by a
      multidisciplinary team involving paediatricians, paediatric urologists,
      physiotherapists, paediatric psychologists are detailed [corrected].

PMID- 11819921
TI  - [Cost of managing cataracts. Evaluation of traditional hospitalization and
      ambulatory surgery].
AB  - OBJECTIVE: Demonstrate eventual differences and evaluate the medical costs of
      treatment of a cataract in traditional hospitalisation and out-patient surgical
      conditions. METHODS: We conducted a study of minimisation costs in 3
      ophthalmologic hospital departments. This retrospective study randomly selected
      the medical files of 250 patients (100 operated in the out-patient surgical
      department and 150 operated in traditional surgical conditions). Costs were
      evaluated on direct hospital costs, according to the standard costs method and
      the method of true costs. RESULTS: The mean total cost of a cataract is of 10,984
      F in traditional hospital conditions and of 7,683 F in out-patient surgical
      conditions. DISCUSSION: In terms of direct hospital costs, treatment of cataracts
      in out-patient surgery appears more economic compared with traditional surgery.
      The difference in cost concerned the fixed hospital charges (structures and
      staff). CONCLUSION: Out-patient surgery will progress in France in the next few
      years, but traditional hospitalisation will still be required in ophthalmologic
      practice.

PMID- 11819922
TI  - [Collagen gastroenterocolitis].
AB  - INTRODUCTION: Collagenous gastroenterocolitis is a recently known rare cause of
      chronic diarrhoea, that raises numerous nosological and diagnostic problems.
      OBSERVATION: A 41 year-old woman was hospitalised for severe diarrhoea, diagnosed
      as collagenous gastroenterocolitis. Gastroscopy and ileocolonoscopy were
      macroscopically normal, but a 20 to 40 microns thick sub-epithelial collagenous
      band was revealed in the gastric, duodenal and colic biopsies. Parenteral
      nutrition and treatment with salazopyrine and prednisolone progressively
      normalised the transit. Three months later, only a 30 microns colic mucosa
      collagenous band persisted. All the biopsies taken during control gastro
      colonoscopy 2 years later were histologically normal. After 5 years follow-up and
      absence of treatment, the patient no longer presented diarrhoea or biological
      abnormality. COMMENTS: This exceptional observation is a reminder that sub
      epithelial collagen deposits are not always limited to the colon and therefore
      justify, in patients with collagenous colitis, systematic gastro-duodenal and
      ileum biopsies.

PMID- 11819923
TI  - [Mediastinal abscess in a child].

PMID- 11819924
TI  - [Typhoid cerebellitis].

PMID- 11819925
TI  - [Toxocariasis].
AB  - A COSMOPOLITAN PARASITIC ZOONOSIS: Toxocariasis is a widespread native
      parasitosis. It is due to the presence of Toxocara-type nematode larvae in the
      organism, that is at the origin of various clinical pictures. Transmitted by dogs
      and more rarely by cats, contamination occurs by ingestion of embryos deposited
      on the ground (animal excrements). MULTIPLE CLINICAL FORMS: The clinical forms
      are non-specific but frequent and varied (neurological, ophthalmologic,
      pulmonary, cutaneous and sometimes rheumatological). DIAGNOSIS: Diagnostic
      presumption is made in the presence of hypereosinophilia, proof of progressing
      toxocariasis. However, this increase is non-specific and is found in many other
      parasitosis. Diagnosis should therefore be confirmed using an IgG ELISA test and
      confirmed by Western Blot. TREATMENT: Currently, there is no consensus regarding
      treatment, however certain data are available in the literature. Prophylaxis
      appears to be the best weapon against this little known disease.

PMID- 11819926
TI  - [Dysthyroidism in elderly patients. Clinical characteristics].
AB  - FROM A CLINICAL POINT OF VIEW: Diagnosis of dysthyroidism in the elderly is
      particularly difficult because of the lack of sensitivity and specificity of
      classical symptoms and examinations. Neuro-mental and cardiovascular signs are
      frequent: dysthyroidism should always be searched for in the presence of
      dementia, depressive syndrome, heart failure or tachyarrhythmia. BIOLOGICAL DATA:
      Simple screening must therefore be widely proposed and relies on complete thyroid
      stimulating hormone (TSH) assay, further completed by free thyroid hormone assay.
      Biological diagnosis is easy in the healthy elderly patient, but interpretation
      of the assays is delicate in the case of intercurrent diseases or treatment with
      amiodarone. THE CAUSES TO BE LOOKED FOR: The detection of hypothyroidism does not
      require etiological exploration, other than the search for iodine overload. In
      cases of hyperthyroidism, scanning usually reveals a nodular goitre. THERAPEUTIC
      REGIMENS: In most cases treatment is simple. Replacement therapy is used for
      hypothyroidism. Patience and cardiovascular monitoring are essential. In the
      absence of iodine overload or compressive goitre, radioactive iodine is the
      treatment of choice. These simple treatments avoid the loss of physical and
      mental autonomy and cardiovascular complications. The importance of screening of
      these so-called "profitable" diseases in the elderly is obvious.

PMID- 11819927
TI  - [Value of D-dimers in diagnosis of acute pulmonary embolism].
AB  - FIBRIN BREAKDOWN PRODUCTS: D-dimers are protein substances resulting from the
      action of 3 enzymes, thrombin, factor XIII and plasmin, on the fibrinogen
      molecules. In the case of thrombosis, all these enzymatic reactions are
      activated, explaining the increase in D-dimer levels induced. The notion of a
      threshold is only significant for a given test; the 500 micrograms/L threshold is
      widely used for tests relying on ELISA methods (enzyme-linked immunosorbent
      assay). FROM A TECHNICAL POINT OF VIEW: The use of D-dimer ELISA in excluding
      pulmonary embolism is now well established. New quantitative tests with latex,
      based on a turbidimetric method, also appear interesting in this context. The
      latter is reliable, rapid, inexpensive, remarkably sensitive (97 to 100%) and
      widely available. INTEREST: Performed in the initial stages of diagnosis in an
      out-patient population with a 20-25% prevalence of the disease, it excludes the
      diagnosis in around 30% of patients. Decisional analysis models have shown that
      this method is economically profitable. However, in elderly hospitalised
      patients, its clinical utility is lesser because of its low specificity in this
      population. The association of high clinical probability of pulmonary embolism
      and normal D-dimer leves is rare and has a weaker negative predictive value, even
      when the ELISA technique is used.

PMID- 11819928
TI  - Negotiating the Data Bank thicket: what payments the dental practitioner need to
      report.

PMID- 11819929
TI  - The Forsyth Institute: a world force in science and health education.

PMID- 11819930
TI  - Criteria for implant selection.

PMID- 11819931
TI  - Serotonin-active drugs.

PMID- 11819932
TI  - Establishing a baseline: medical health history and other patient record
      considerations.

PMID- 11819933
TI  - The Bagby Sagittal.

PMID- 11819934
TI  - Looking at cranial distortions.

PMID- 11819935
TI  - How to promote & provide functional jaw orthopedics.
AB  - This article outlines how to promote and provide Functional Jaw Orthopedic (FJO)
      treatment, which is unique medical dentistry. FJO treatment is valuable
      preventive and therapeutic medical dentistry because jaw treatment impacts the
      extensive structures that surround the human airway and adjoin the skull. To best
      provide the broad range of unique FJO treatments, dentists need extensive
      knowledge, skills and experience. In order to promote FJO treatments, dentists
      and other interested health care providers need a wide assortment of educational
      materials that clearly show FJO treatment options and benefits.

PMID- 11819936
TI  - A history of a TMJ survivor.

PMID- 11819937
TI  - TMD stabilization: orthodontic finishing success.

PMID- 11819938
TI  - In search of the rubber ball.

PMID- 11819939
TI  - Sharp pencils and telling points.

PMID- 11819940
TI  - National Children's Dental Health Month.

PMID- 11819941
TI  - Early childhood caries: etiology, risk assessment, and prevention.

PMID- 11819942
TI  - Compare today's single-visit endodontics with the old "Sargenti Technique".

PMID- 11819943
TI  - Views relative to the current arguments concerning the Sargenti technique and its
      use in the United States.

PMID- 11819944
TI  - Bleaching discoloured teeth.
AB  - The bleaching of teeth has encountered some legislative problems over the past
      few years but it is now possible to use both vital and non-vital bleaching
      techniques in the UK. Hydrogen peroxide has a long history of use and would
      appear to be safe to use to change the appearance of discoloured teeth. It is
      conservative of tooth tissue and may delay the need for more invasive veneers and
      crowns. This article describes some of the methods of bleaching using hydrogen
      peroxide that are currently available.

PMID- 11819945
TI  - Current practice in endodontics: 5. Obturation.
AB  - The aim of this series of six articles is to improve the quality of endodontic
      treatment in general dental practice by considering what is currently being
      taught in dental schools. This article first considers the possible reasons for
      persisting symptoms following preparation of the root canals. It then reviews the
      many and varied methods of obturating the prepared root canal system that are
      available to the general dental practitioner. By considering the objectives of
      their treatment, and their own level of expertise, readers may decide that one or
      more new techniques may benefit their practice.

PMID- 11819946
TI  - Dental erosion: a case study of a marathon runner.
AB  - This paper presents a case study of a recreational runner who unwittingly has
      caused severe damage to her dentition through her lifestyle and dietary habits.
      It should serve as a reminder to all dental practitioners that dental problems
      occur even in patients who seem to be following a healthy lifestyle.

PMID- 11819947
TI  - Transcultural oral health care: 6. The oral health of minority ethnic groups in
      the United Kingdom--a review.
AB  - The 1991 census of England and Wales estimated that the minority ethnic
      population was almost 2.95 million, or 6% of the total population of the UK. The
      aim of this paper is broadly to describe the oral health status and trends among
      minority ethnic groups to enable a clearer formulation of strategies to improve
      their oral health.

PMID- 11819948
TI  - Toothbrushing: why, when and how?
AB  - Toothbrushing is a widely practiced oral healthcare habit which, in conjunction
      with fluoride toothpaste, can help to prevent dental caries and periodontal
      disease. The effectiveness of toothbrushing is dependent on many different
      factors including frequency and duration of brushing, rinsing habits and brush
      type. Knowledge of how these factors influence effectiveness will allow the
      dental professional to give appropriate advice.

PMID- 11819949
TI  - Surgical forceps techniques.
AB  - This paper considers two new elevator and dental forceps techniques for the
      atraumatic removal of teeth to avoid a surgical procedure where possible. The
      techniques described should be applicable in relatively well defined but commonly
      occurring situations. The two techniques involve the unconventional use of
      conventional dental extraction forceps, with the aim of facilitating removal of
      the retained roots of certain teeth: the first for incisors, canines and
      premolars and the second for lower first molars. The term 'surgical forceps
      technique's is tentatively put forward as a description of these hybrid
      procedures.

PMID- 11819950
TI  - New regenerative technologies: rationale and potential for periodontal
      regeneration: 1. New advances in established regenerative strategies.
AB  - Regenerative techniques have been clinically available for over a decade, but
      with limited success in promoting new bone, cementum and connective tissue
      attachment. New understanding of the tissues involved in regeneration and of the
      materials used to promote regeneration have led to new advances. This is the
      first of two articles that discusses new regenerative technologies with respect
      to their rationale and potential for periodontal regeneration and focuses on root
      conditioning, bone grafts and bone substitutes, and guided tissue regeneration.

PMID- 11819953
TI  - National Adult Oral Health Survey 2000/01.

PMID- 11819955
TI  - Lip-biting in patients with profound neuro-disability.
AB  - Profound neuro-disability due to severe brain damage affects approximately 1200
      people per year in the UK. Approximately half of these patients exhibit
      exaggerated or abnormal oral reflexes. Biting, bruxism and ruminating movements
      may result in dental or soft tissue trauma, with severe lip or tongue
      lacerations. This paper describes 10 patients referred to the dental department
      at the Royal Hospital for Neuro-disability with lip bites and/or severe bruxism,
      during a 12-month period. Management options include: monitoring the lesion;
      smoothing teeth; providing a bite raising appliance; or extracting teeth. This
      paper discusses the difficulty in management of lip trauma in this group of
      patients and emphasizes the importance of an interdisciplinary approach.

PMID- 11819956
TI  - An elusive success!

PMID- 11819957
TI  - New models for administering UK dental care.

PMID- 11819958
TI  - What is a dental access centre?

PMID- 11819959
TI  - New regenerative technologies: rationale and potential for periodontal
      regeneration: 2. Growth factors.
AB  - Regenerative techniques have been clinically available for over a decade,
      although success in promoting new bone, cementum and connective tissue attachment
      has been limited. New understanding of the tissues involved in regeneration, and
      of the materials used to promote regeneration, have led to new advances. This is
      the second of two articles discussing new regenerative technologies with respect
      to their rationale and potential for periodontal regeneration. This article
      focuses on growth factors, and in particular bone morphogenetic proteins.

PMID- 11819960
TI  - The benefits of toothpaste--real or imagined? Review of its role in tooth
      whitening.
AB  - The market for whitening toothpastes in the UK is burgeoning at present, but
      little has been published about the modes of action or efficacy of such pastes.
      Much is known about how the individual ingredients work, but toothpaste
      formulations are complex and there is potential for interaction. Studies have
      been undertaken to compare the efficacy of various test products, but these have
      used different types of trial design and consequently direct comparisons are
      difficult, not least because there are several ways of measuring 'whiteness', and
      there is no consensus of opinion between workers in this field as to the best way
      to record it.

PMID- 11819961
TI  - Murmurs, infective endocarditis and dentistry.
AB  - Patients with cardiac murmurs may have a predisposition to infective
      endocarditis, and the dental practitioner must be aware of this potential
      problem. This article reviews cardiac murmurs and how they are investigated by
      physicians to assess their significance. Practical advice is offered concerning
      the need to refer patients with a suspected heart murmur. The emergency and
      elective dental management of patients with heart murmurs is included, together
      with recommended regimens for antibiotic prophylaxis.

PMID- 11819962
TI  - Preparation guidelines for full and partial coverage ceramic restorations.
AB  - Aesthetic awareness of dental patients has produced a growing demand for
      posterior tooth-coloured restorations. This has led to the development of
      posterior composite resins and, more recently, posterior all-ceramic
      restorations. In the last decade, modern technological advances have allowed the
      production of stronger ceramics and better luting techniques, which have led to
      the use of all-ceramic restorations in posterior sites. The preparation
      guidelines for posterior ceramic restorations outlined in this paper emphasize
      rounded internal line angles and a chamfer or rounded shoulder finish-line.

PMID- 11819963
TI  - Current practice in endodontics: 6. Retreatments and periradicular surgery.
AB  - The prime aim of this series of six articles has been to improve the quality of
      endodontic treatment in general dental practice by considering what is currently
      being taught in dental schools. This final article considers what may go wrong
      following completion of root canal treatment, whether orthograde retreatment is
      possible and how it may be achieved, and if or when periradicular surgery may be
      indicated.

PMID- 11819964
TI  - Does orthodontics damage faces?
AB  - With the increasing provision of orthodontic care in this country, certain
      practitioners have raised concerns regarding the use of elective extractions and
      retraction mechanics, especially the effects on the facial profile and the TMJ.
      The non-extraction versus extraction debate spans the history of orthodontics,
      and the concepts of facial attractiveness are subject to change as fashions
      change. Within the realms of evidence-based practice, there is little or no
      evidence to suggest that the philosophies and mechanics of contemporary
      orthodontics, in the vast majority of cases, cause damage to the profile or are
      directly linked to the development of TMJ dysfunction.

PMID- 11819965
TI  - Low cost diagnostics.

PMID- 11819966
TI  - House of mirrors in the virtual ICAAC.

PMID- 11819967
TI  - What a difference a day makes.

PMID- 11819968
TI  - Seeking disclosure.

PMID- 11819969
TI  - Working my last nerve.

PMID- 11819970
TI  - Low-dose adefovir for the treatment of chronic hepatitis B in HIV-infected
      people.

PMID- 11819971
TI  - A question of space: options for the restorative management of worn teeth.
AB  - The prevalence of tooth surface loss has increased in recent years. The essence
      of management is an effective preventive regime; however, in many instances
      restoration may also be necessary. A number of strategies is available for
      creating sufficient space to enable restoration and several techniques for
      restoration known. This article reviews the significance of the vertical
      dimension of occlusion and describes the restorative management of a patient
      affected by severe tooth wear.

PMID- 11819972
TI  - Magnification: what is available, and will it aid your clinical practice?
AB  - With the development of clinical techniques that require high levels of manual
      dexterity and involve fine detail, there is increasing interest in the use of
      magnification for dental procedures. This article considers the potential
      benefits of magnification, the different methods by which it can be obtained and,
      finally, presents some caveats to its use.

PMID- 11819973
TI  - Oral candidosis.
AB  - Oral candidoses are frequently encountered in the practice of dentistry. Although
      most oral candidoses are symptomless, the can indicate the presence of an
      underlying systemic disease, and the persistence of oral candidosis following
      appropriate conventional management may be one of the first signs of undiagnosed
      immunosuppression. The opportunistic pathogen Candida albicans is the most
      commonly isolated species from oral candidal lesions; however, the non-albicans
      Candida spp. are also implicated in the aetiology of oral candidoses. The
      effective management of oral candidosis is dependent on an accurate diagnosis,
      identification and elimination of any predisposing factors (where possible), and
      the prescription of either topical or systemic antifungal agents. Oral candidosis
      may have significant implications for the general health of immunosuppressed
      patients, particularly when caused by the non-albicans spp. and, in cases of
      severe immunosuppression, systemic candidosis can be life-threatening. This
      article outlines the clinical presentation and appropriate management for the
      commonly presenting oral candidal conditions.

PMID- 11819974
TI  - The contribution of industry to the decline in dental caries.
AB  - The contribution of the oral care industry to the reduction in dental caries
      extends beyond the provision of safe and clinically proven products containing
      fluoride. The industry has contributed to the scientific base that underpins the
      use of fluoride, delineated factors that influence the clinical performance of
      toothpaste, raised the public's awareness of dental health and provided funding
      to support both undergraduate and postgraduate students in clinical training and
      basic research.

PMID- 11819975
TI  - The benefits of toothpaste--real or imagined? The effectiveness of toothpaste in
      the control of plaque, gingivitis, periodontitis, calculus and oral malodour.
AB  - Toothbrushing with toothpaste is the most widely used method of home dental care
      for the populations of the Western world. The traditional role of toothpaste is
      primarily cosmetic, in aiding the cleaning of teeth and producing fresh breath.
      Today, however, formulations contain ingredients which may also help oral health
      by way of reducing dental plaque and improving gingival/periodontal health. This
      article provides a short review on the usefulness of these chemicals when used
      primarily in toothpastes.

PMID- 11819976
TI  - Down's syndrome and oral care.
AB  - Down's syndrome is caused by a chromosomal abnormality and is characterized by
      certain physical, mental and medical features. A number of these features, such
      as learning disability, cardiac anomalies and an altered immune system, can have
      a profound effect on oral health and the delivery of oral care. In turn, this can
      affect social acceptability and quality of life. The optimum potential of the
      person with Down's syndrome is achieved via a multidisciplinary approach that
      involves the members of the dental team from an early stage.

PMID- 11819977
TI  - A case study demonstrating the use of natural teeth on a denture.
AB  - The ability to use natural teeth on a denture can yield the most natural and
      pleasing results, helping a patient to adapt quickly to wearing dentures. A
      number of workers have demonstrated their success with this technique. This case
      study shows another example of how favourable the results can be.

PMID- 11819978
TI  - [Impacted maxillary cuspid. I. Etiology and diagnosis].
AB  - Attention is paid to the normal and disturbed eruption of the upper cuspid.
      Genetic factors seem to play the most important role in impaction or delayed
      eruption. The dentist needs to be aware of the diagnostic and roentgenological
      features of this phenomenon.

PMID- 11819979
TI  - [Prostate cancer].

PMID- 11819980
TI  - [Teeth at birth (natal teeth)].

PMID- 11819981
TI  - [Saliva research: now and in the future].
AB  - In the near future salivary research will most likely play a rather important
      role in daily dental practice. The dentist will be expected to gather data
      concerning the patient's nutrition, medical history, oral complaints and
      xerostomia as perceived by the patient. In addition he may perform the following
      plain measurements: secretion rate of whole saliva in resting condition and after
      stimulation, and some parameters of importance for caries. The biochemical
      analysis of whole saliva and glandular salivas can be performed only in
      specialized laboratory. New developments are to be expected on the field of
      biotechnical synthesis of salivary protective factors, that is to say, histatins
      and cystatins in the nearby future and mucins on the longer term. New saliva
      substitutes and mouth rinses will be made on the basis of these artificially made
      proteins, not only to relieve xerostomia, but also to prevent oral infection and
      inflammation.

PMID- 11819982
TI  - [Dry mouth; possible cause--pharmaceuticals].
AB  - Many elderly complain about oral dryness. This complaint can be the result of the
      use of drugs, because many drugs, such as anti-depressives, anti-psychotics and
      anti-hypertensives, have an anti-cholinergic or anti-adrenergic action. Knowledge
      of this potential side-effect of drugs as well as adjustment of schedules of drug
      usage may result in (partly) relief of dryness-related complaints. In this paper
      first of all mechanisms that underly negative regulation of salivary secretion
      are discussed. An overview is given of drugs with an salivary secretion
      inhibitory action. In addition, suggestions are presented to manage drug-induced
      hyposalivation.

PMID- 11819983
TI  - [The functions of saliva].
AB  - Saliva is crucial in maintaining the oral health. The watery, viscous phase of
      saliva solubilizes the various substances and prevents the oral surfaces against
      desiccation. An agent is tasted only when present in a soluble state. The
      electrolytes of the saliva are essential as a buffer (bicarbonate and phosphate)
      and they are involved in the remineralization of the tooth enamel.

PMID- 11819984
TI  - [Saliva, a physiological medium].
AB  - Plaque and plaque fluid, rather than saliva, are of prime importance in
      determining the result of the interaction between tooth enamel and its
      environment. The concentration of calcium and phosphate ions is higher in plaque
      fluid than in saliva. Local supersaturation may result in the remineralization of
      white spot lesions or in the formation of calculus. The latter may be inhibited
      with containing dentifrices. Undersaturation, resulting from bacterial acids
      production, promotes dental caries. Fluorides are effective against caries,
      although the limited transporting properties of saliva would be recognized when
      designing caries preventive treatments. Suppleting saliva with calcium and
      phosphat ions through mouthrinses is another method to fight caries, while
      stimulation of the secretion by chewing gum is also very effective.

PMID- 11819985
TI  - [Saliva, caries and diagnostics].
AB  - During the last decades the proportion of children without tooth decay and dental
      restorations has strongly increased. Yet, some patients show rampant caries or a
      sudden progression of decay into the dentin. In order to intervene adequately in
      such cases, it is of importance to determine first of all the underlying causes.
      Indicators have been developed to predict the progression of caries. By
      determining the amount of fluoride in the dental plaque one gets insight into the
      fluoride regime of the patient. One may also determine numbers of caries
      pathogenic bacteria in saliva samples, as can now be done with commercially
      available kits for S. mutans and lactobacilli. The buffering capacity of saliva
      can also be determined. Although none of these tests have a high predictive
      value, they are useful in explaining sudden changes in caries activity and to
      formulate preventive schemes.

PMID- 11819986
TI  - [Diagnostic value of saliva].
AB  - Sialometry and sialochemistry can be valuable tests in clinical circumstances.
      The application in the dental office, however, is limited. There is good
      sensitivity in differentiation from normal function. The specificity may be
      regarded as low related to classical nosology, because many diseases have a
      number of fundamental processes in common. Comparison of values from the right to
      the left side is reliable. The tests are valuable tools in monitoring in
      particular during and after irradiation. The laboratory evaluation of the
      glandular function requires simultaneous blood-chemistry. This noninvasive
      technique of investigation is indicated in salivary disorders as well as in
      pathology of the oral mucosa and the periodontium. Both sialometry and
      sialochemistry are a must in complaints of xerostomia, sialorrhea and the burning
      mouth syndrome. It is of special interest with respect to circulatory disorders
      of the glands and the use of medicaments. A special salt retaining disorder of
      the glands, the non-sal-saliva syndrome is described.

PMID- 11819987
TI  - [Cause, effects and treatment of hyposalivation].
AB  - Adverse effects of drugs, radiotherapeutic treatment of head and neck tumors and
      Sjogren's syndrome are common causes of hyposalivation. The resulting sequelae
      include oral dryness, burning mouth, impeded oral functions, nocturnal oral
      discomfort and an increased incidence of rampant caries and oral infections.
      Causal therapy is only occasionally applicable. The main causes, consequences and
      management of hyposalivation are described.

PMID- 11819988
TI  - [Saliva and dentures].
AB  - Saliva plays an important role in the functioning of full dentures. A prosthesis
      does not rest on bare mucous membranes but on an interposed salivary film. This
      pellicle, mainly consisting of mucin glycoproteins, protects the tissues from
      injury caused by the denture base. The retention of the complete upper denture,
      and in a lesser degree of the lower, is also dependent on the salivary layer
      between the denture base and the oral tissues. A combination of several physical
      factors results in an adhesion. In order to achieve an optimal effect of these
      adhesive forces, the manufacturing of the dentures as well as the long term
      aftercare should meet a number of requirements, described in this article.

PMID- 11819989
TI  - [The drug addict and the dentist].
AB  - An impression of the dental treatment of the addict is given. Both the patient's
      relationship to the dentist, as well as the specific condition of the addicted
      patient with the remarkable characteristics are discussed.

PMID- 11819990
TI  - [Multiple sclerosis].

PMID- 11819991
TI  - ["Did I do something wrong?" Palatal necrosis due to local anesthesia].

PMID- 11819992
TI  - [What to do with aphthous ulcers?].

PMID- 11819993
TI  - [Repair of residual cleft palates in older adult patients].
AB  - Residual cleft palates in adult patients are hard to repair. A prosthesis may
      cause patients to complain of loss of fluid through the nose when they drink.
      Furthermore, there may be problems with the retention of the prosthesis. In
      sixteen adult patients the residual cleft palate was successfully closed. In
      three patients a second surgical procedure was required.

PMID- 11819994
TI  - [Breast cancer].

PMID- 11819995
TI  - [Impacted maxillary cuspid. III. Orthodontic aspects].
AB  - Delayed eruption of impacted canines in more or less guaranteed by using the
      modified window technique. A decision for futher treatment can be made
      afterwards. If orthodontic treatment is required, fixed appliance is recommended
      for uneventful orthodontic positioning of these teeth.

PMID- 11819996
TI  - [Kidney transplantation].

PMID- 11819997
TI  - [Ultrasonic instrumentation versus hand instrumentation in periodontics. A review
      of the literature].
AB  - The working mechanism and the correct use of ultrasonic devices is discussed.
      Comparative efficiency of ultrasonic and hand instrumentation is evaluated for
      the removal of subgingival plaque and calculus, for the effect on root surfaces
      and for the ability in removing endotoxins. Possible side effects of the
      ultrasonic vibrations on the tooth structures and periodontal tissues, the
      incidence of bacteremias and the spreading of oral infections via aerosols are
      stated. Particular attention is given to the clinical results of both
      instrumentation technics and the necessity of root planing. One can conclude,
      that ultrasonics present an alternative and/or a supply for hand instruments,
      provided that a selective and careful use is taken into account.

PMID- 11819999
TI  - [Pericoronitis].

PMID- 11819998
TI  - [Rheumatoid arthritis].

PMID- 11820000
TI  - [The making of an overdenture supported by two endosseous implants in the lower
      jaw].
AB  - Due to extreme alveolar resorption many edentulous patients wearing complete
      dentures suffer from loss of function of the orofacial system. Improvement of
      oral functions can be obtained by increasing the denture-support, using implants.
      The construction of a combined implant/mucosal supported lower overdenture will
      be helpful. A method to construct an overdenture on oral implants is described.

PMID- 11820001
TI  - [Treatment and prevention of osteoporosis].

PMID- 11820002
TI  - [Ulcer caused by orthodontic instruments?].

PMID- 11820003
TI  - [The impression procedure for overdentures supported by two endosseous implants
      in the lower jaw. A comparison among three permucosal implant systems].
AB  - The procedure to make an impression for the construction of an overdenture on
      endosseous implants in the lower jaw is not the same for all implant systems.
      Impression-procedures for a two-phase screw type implant (Branemark), a two-phase
      cylinder type implant (IMZ) and a one-phase implant (ITI Bonefit) are described.

PMID- 11820004
TI  - [Systemic lupus erythematosus].

PMID- 11820005
TI  - [A red spot on the tongue].

PMID- 11820006
TI  - [Composite or amalgam? Not a black or white decision].
AB  - Amalgam as a restorative material in dentistry is discussed because of believed
      toxic properties of the material, yet there is no scientific prove for the
      assumption. Adhesive restorations are a possible alternative for amalgam in
      restoring posterior teeth. For treatment of primary caries, the direct composite
      resin restoration has many advantages. When greater defects are to be restored,
      adhesive composite resin restorations become less favourable. At this moment no
      long term results are available for indirect adhesive techniques. For the time
      being it seems necessary to use composite resin as well as amalgam for the
      restoration of posterior teeth.

PMID- 11820007
TI  - [Systemic sclerosis].

PMID- 11820008
TI  - [Lichen planus: what to do?].

PMID- 11820009
TI  - [Germectomy. The germ of the third mandibular molar in children: remove or
      preserve?].
AB  - Third molars are often removed in order to prevent complications and various
      other problems associated with impacted third molars and their removal. Abortion
      of mandibular third molars is a procedure carried out at an early age in those
      subjects where there is insufficient room for the eruption of the third molars.
      On the other hand one can also decide to remove the second molars and to annexate
      orthodontically the third molars in the arch.

PMID- 11820010
TI  - [Impacted teeth].
AB  - Prevention of impaction depends in many cases on the knowledge of variations in
      eruption sequences. However, in case of impaction, spontaneous eruption can be
      stimulated by exposing the tooth with the modified window-technique. Frequent
      communications between dentist, orthodontist and oral surgeon are required to
      determine the right time of intervention.

PMID- 11820011
TI  - [Autotransplantation of teeth].
AB  - Autotransplantation of teeth has become a common procedure in oral surgery. The
      most usual procedures are autotransplantation of premolars, canines and third
      molars. The method can be performed on young patients in combination with
      orthodontic treatment, creating optimal occlusal relationship. Indication,
      selection and timing in connection with the surgical procedure are of paramount
      importance for optimal results.

PMID- 11820012
TI  - [Dento-alveolar injuries].
AB  - Most dento-alveolar traumas can be managed by the dentist-general practitioner.
      Still, there are some specific injuries which should be treated by dental
      specialists. Some specific guidelines are given for the combined surgical
      orthodontic treatment of fracture of the coronal part of the root, intrusive
      luxation, abnormal position of the permanent tooth due to traumatic displacement
      of the deciduous tooth, ankylosis and tooth loss.

PMID- 11820013
TI  - [Diagnosis of dento-skeletal deformities].
AB  - The diagnosis of dento-skeletal deformities is discussed. The suggestion has been
      made to use a simple classification, which leaves room for a descriptive
      diagnosis. The descriptive diagnosis should include aspects related to the
      maxillofacial skeleton, the soft tissues and the dentoalveolar part. A soft
      tissue analysis will help to assess the main deformity which is often a
      combination of factors, frequently located in both jaws. A recommendation is made
      to include a physical therapist, speech therapist and psychologist in the team.

PMID- 11820014
TI  - [Treatment of dento-skeletal anomalies. Class II occlusion].
AB  - With the combination of orthodontics and oral surgery a skeletal distorelation
      can be treated with a predictable result. A prerequisite for this is a good
      mutual consultation, in which information for the patient has a central role. To
      guarantee this a seven-steps procedure is developed and described. Essential
      aspects of presurgical and postsurgical orthodontics are discussed. Possibilities
      of surgical correction are described.

PMID- 11820015
TI  - [Orthodontic and surgical aspects. Class III malocclusion].
AB  - Skeletal Class III malocclusions are the result of deficient maxillary growth,
      excessive mandibular growth or a combination of both. Vertical as well as
      transverse dimensions can be disturbed too. Skeletal, dental and functional
      characteristics are described briefly. Treatment planning is outlined with
      special reference to the pattern of development during different growth stages
      and its consequences for therapeutical intervention. At last possibilities and
      limitations of surgical/orthodontic correction of the skeletal discrepancy and
      its dental compensations are discussed.

PMID- 11820016
TI  - [Anterior open bite].
AB  - In almost 50% of the Dutch population, the mandibular incisors do not contact the
      maxillary ones. An open bite is usually based on an interposition of the tongue
      and can be combined with other functional disturbances as digit sucking. A large
      open bite with an excessive facial deformity can be treated adequately, after
      facial growth is completed, by a combined orthodontic-surgical approach, in which
      a good cooperation between the orthodontist and the oral surgeon is essential.
      The correction of the facial deformity is of a permanent nature. That does not
      always apply to the open bite due to interposition of the tongue. Often it is not
      possible to arrive at complete contact by orthodontic or surgical means. The
      improvement realized can fade away partly in the years following.

PMID- 11820017
TI  - [Orthodontic and surgical aspects of cleft palate treatment].
AB  - The growth pattern of the face in cleft lip and palate patients is determined by
      intrinsic, functional and iatrogenic factors. Probably the iatrogenic factors are
      the most important. Orthodontic and orthognatic aspects of cleft palate treatment
      are described, being divided in five stages: 1. presurgical orthopedic treatment
      prior to lipclosure; 2. early orthopedic treatment of maxillary hypoplasia; 3.
      reconstruction of the alveolar cleft with bonegrafting and/or orthodontic
      treatment; 4. orthodontic treatment and 5. combined surgical/orthodontic
      treatment.

PMID- 11820018
TI  - [Treatment of syndromes with abnormalities of the face].
AB  - A standard method of treating syndromes with anomalies in the face does not
      exist. Not only are the differences between the symptoms of different syndromes
      very important. Also within one syndrome variations can be marked. A team of
      specialists supports the cranio-facial surgeon in his central role when treating
      these patients. Type of treatment, sequence, timing, et cetera, follow certain
      rules, which may be in part the same as for the treatment of 'ordinary' maxillo
      mandibular disharmonies, but sometimes differ significantly from it. The most
      important aspects of treatment of three rather frequently seen cranio-facial
      syndromes are given. Incidence, symptoms, therapeutical possibilities and timing,
      and results are discussed as well as the necessity of this kind of surgery.

PMID- 11820019
TI  - [Flouroquinolones of the third and fourth generations].
AB  - Levofloxacin, levorotatory isomer of ofloxacine, is the only FQ3G on the belgian
      market since the middle of 2000 and is a little more efficient than the FQ2G
      against S. pneumoniae. The FQ4G are in vitro active against the common and atypic
      respiratory pathogenes and significantly more efficient against the Gram positive
      cocci, principally against S. pneumoniae. Their long duration of action allows
      one oral administration a day sufficient to obtain bactericidal levels in the
      serum. Their secondary effects are located principally at the level of digestive
      tract, neurologic system or cutaneous area. In the U.S.A., several FQ4G (clina-,
      grepa-, spar-, trova-floxacin) were withdrawn from use after observance of severe
      toxicity, while there were being administrated on a large scale. Furthermore, two
      of these "respiratory" FQ4G (gemi- and moxifloxacin) should reinforced our
      therapeutic armoury, moxifloxacin as of 2002 and gemifloxacin as of 2004. The
      position of FQ3G and 4G are in discussion. In the case of pneumonia acquired in
      the community and confirmed by X-Ray, our recommendation is to administer a new
      FQ at the first choice if the patient is allergic to penicillin, debilitated or
      if a penicillin resistant S. pneumoniae is suspected (epidemiology, recent
      antibiotherapy) and at the second choice if it is resistance to penicilline or to
      macrolide, in case of atypic pneumonia. Today, the majority of the pneumonia
      acquired outside the hospital is empirically treated with a betalactam (oral or
      intravenous), with or without macrolide. The new FQ are important drugs. One must
      avoid overprescription which leads to bacterial resistance (especially S.
      pneumoniae).

PMID- 11820020
TI  - [All plants aren't roses].

PMID- 11820021
TI  - [Influence of the bonding interface on bracket adhesion].
AB  - Adhesion strength may be explained by different theories that allow a better
      understanding and a better use of orthodontic adhesives. Transmission (TEM) and
      scanning (SEM) electron microscopy analysis of debonding areas allows to
      differentiate the location of bonding fractures and the consequences on enamel.
      Such a knowledge may be useful when choosing the most adapted protocol.

PMID- 11820022
TI  - [Prevalence of dental agenesis: a radiologic and clinical study in Dakar].
AB  - A total of 1007 files were studied with regard to the prevalence of congenitally
      missing teeth. All patients were radiographed. 4.56% were found to have at least
      one congenitally missing tooth. The lower second premolar was the most commonly
      missing tooth in this study (41.66%), followed by the upper lateral incisor
      (22.2%). The prevalence and the distribution of dental agenesis between male and
      female was similar.

PMID- 11820023
TI  - [Hyperactivity of the muscles of the lip and chin and indications for surgery to
      reduce it].
AB  - Hyperactivity of the muscles controlling the lower lip and chin (muscles of the
      chin, buccinator, orbicularis, etc.) can be demonstrated at different levels of
      the muscular complex and may act as an elastic force against the mandibular
      alveolar process. Dysfunction in this region may lead to reduction of the
      alveolar bone quantity, reducing the tooth-bone equilibrium. If this balance is
      disturbed, periodontal lesions, a lower incisal crowding and a retrognathic
      mandibular process may result. Surgery to correct overactivity of the chin
      muscles is described here step by step. Resection of the muscles may be
      undertaken on a greater or lesser scale and striation of the muscle may also
      allow reduction of muscular strength. Reducing the muscular activity creates a
      better environment for the development of the mandible and its alveolar process.
      Depending on the clinical situation, these techniques can be associated with
      genioplasty, bone graft and/or mandibular orthognathic surgery.

PMID- 11820024
TI  - [Discussion of the report: Treatment during the mixed dentition and muscular
      equilibrium].

PMID- 11820025
TI  - [Discussion of the report: Treatment during the mixed dentition and muscular
      equilibrium].

PMID- 11820026
TI  - [Discussion of the report: Treatment during the mixed dentition and muscular
      equilibrium].

PMID- 11820027
TI  - [Discussion of the report: Treatment during the mixed dentition and muscular
      equilibrium].

PMID- 11820028
TI  - [The distal active concept applied to the mixed dentition: a comparative study].
AB  - The "Distal Active Concept" (DAC) therapy used during the mixed dentition period
      shows a mandibular growth of 7.6 mm whereas the same treatment applied on the
      permanent dentition only shows a mandibular growth of 3.9 mm. This difference is
      highly significant. The DAC therapy is prescribed to a group of 30 nine years old
      patients with a mixed dentition for six months. The DAC therapy is prescribed to
      a group of 34 twelve years old patients with a permanent dentition for 24 months.
      As the mandibular answer to treatment seems to be more effective at the age of 9
      than later, during the prepubertal period, the DAC therapy appears to be of
      interest and an alternative to activator treatments. Our results show the
      efficiency of a first stage treatment, for all the patients showing a significant
      class II malocclusion.

PMID- 11820029
TI  - [Orthodontic treatment of overbite by the Tip Edge technique in conjunction with
      an anterior bite elevator. Part 1].
AB  - In orthodontics, incisor overbite has always been considered as an anomaly
      difficult to correct but also as the one most hindering the solving of the
      problems resulting from other associated malpositions. The recent concept of
      unlocking, introduced by the bioprogressive School, proves that the profession
      has become aware of its importance in any orthodontic treatment plan. Due to the
      fact that overbite also hinders the setting up of inferior brackets or forces the
      practitioner to bond them in a position liable to burden the parodontal health of
      the lower incisors has therefore induced the author to put in place, at the
      beginning of the treatment with the Tip-Edge technique, an anterior bite raiser
      thus generating space in the lateral sectors. Considering how fast the anterior
      problem is solved once the occlusion is lifted, the bite raiser can be suppressed
      within three months. Another advantage resides in the possible adjunction of an
      expansion screw also aimed at unlocking the occlusion in transverse direction.
      The question then raised in to know whether that approach which ought to be
      compared to the one of the functional appliances is not the ideal solution to
      unlock the occlusion in the three dimensions of space when the use of fixed
      appliances alone might be unsuitable or too slow, regarding current therapeutic
      aims. Attributing that spectacular therapeutic result to an incisor intrusion or
      a molar extrusion is of little interest as far as those alterations do not lead
      to an increase of the vertical dimension of the lower portion of the face. A
      cephalometric study, published concomitantly, has evidenced that the use of an
      anterior bite raiser together with the Tip-Edge technique only leads to perfectly
      similar alterations to those observed with the Ricketts bioprogressive technique
      or the Schudy edgewise technique, without the help of a bite raiser. From now on,
      integrating the bite raiser in our therapeutic armamentarium in conjunction with
      fixed techniques is highly recommended.

PMID- 11820030
TI  - [Orthodontic treatment of overbite with an appliance for raising the anterior
      vertical dimension. Part 2].
AB  - If incisor overbite in the matter of orthodontic treatment entails difficulties
      with the appliances due to excessive overbite of the incisors, involving an
      anterior bite raiser to enable the unlocking of the occlusion and the bonding of
      the brackets on the anterior mandibular teeth poses the problem of the vertical
      behavior of the masticatory apparatus during treatment. A profile teleradiograph
      was therefore taken at the beginning of treatment and again once the occlusion
      had been lifted due to the presence of the bite raiser and within a period of
      three months. The sample was separated in two groups according to the value of
      FMA; a first group was composed of 44 cases exhibiting an FMA angle inferior to
      25 degrees therefore similar to the cases analyzed by Dake and Sinclair in 1989,
      called "reference group" and a group of cases exhibiting an FMA angle superior to
      25 degrees. The aim of this study is indeed to confront, as regards vertical
      behavior, the therapeutic approach of the authors with the one studied by Dake
      and Sinclair dealing with cases treated with Ricketts and Tweed technique (Schudy
      modified). Following Dake and Sinclair's approach, the authors managed to find
      out in cases with FMA inferior to 25 degrees that the vertical alterations in the
      study group were not different from those in the reference group. This means that
      in spite of the presence of an anterior bite raiser the mandibular plane angle
      had only increased by 1.8 degree, compared to 1.8 degree for the Ricketts group
      and 1.1 degree for the Tweed/Schudy group. As for the study sample with an FMA
      angle superior to 25 degrees, the vertical alterations in the study group show an
      increase of the angle of the mandibular plane equal to 1.2 degree, here again the
      increase is similar to the one observed in the reference group. It can thus be
      concluded that the use of an anterior bite raiser in conjunction with the Tip
      Edge technique is not only advisable but strongly recommended both to unlock the
      occlusion but also to enable bracket bonding at the very beginning of treatment.

PMID- 11820031
TI  - [Image of the month. Extensive vena cava thrombosis and massive pulmonary
      embolism despite the presence of a vena cava filter and an optimal
      anticoagulant].

PMID- 11820032
TI  - [How I treat ... ascites].
AB  - Ascites is the most common of the major complications of cirrhosis. The initial
      evaluation of a patient with ascites should include a history, physical
      evaluation and some investigations. Treatment should consist of treating the
      underlying liver disease, sodium restricted diet (2 g of Na+/day) and diuretics.
      This regimen is effective in 90% of patients. The treatment options for the
      diuretic resistant patients include serial therapeutic paracentesis,
      peritoneovenous shunting, TIPS and liver transplantation. The treatment and
      prophylaxis of spontaneous bacterial peritonitis which is a frequent and severe
      complication in cirrhotic patients with ascites is also important. The
      differential diagnosis with secondary bacterial peritonitis is essential because
      the latter usually does not resolve unless patients are surgically treated.

PMID- 11820033
TI  - [Clinical case of the month. Natural history of morbid obesity: towards insulin
      requiring type 2 diabetes and reversal after bariatric surgery].
AB  - Morbid obesity is a crucial risk factor in the development of type 2 diabetes and
      is often associated with a metabolic syndrome closely linked to insulin
      resistance. This case report illustrates the natural history of morbid obesity,
      starting during the adolescence and ending with an extremely severe type 2
      diabetes at the age of 40. Numerous attempts of weight loss with various medical
      approaches failed and diabetes mellitus rapidly became insulin-requiring in a
      context of extreme insulin resistance. Finally, the patient was submitted to a
      gastric bypass which resulted in a drastic weight loss over 50 kg during the year
      following surgery without any significant side-effects or complications. Type 2
      diabetes almost disappeared and the classical markers of insulin resistance were
      markedly improved. This clinical case clearly demonstrates that successful
      management of obesity with bariatric surgery can reverse severe type 2 diabetes.

PMID- 11820034
TI  - [Ventricular septal defect and recent myocardial infarction].
AB  - Rupture of the interventricular septum is a classical complication of acute
      myocardial infarction. The diagnosis should be evoked when the patient's
      hemodynamic condition deteriorates in the presence of a new systolic murmur. A
      transthoracic or, preferably, transesophageal echocardiography confirms the
      diagnosis. Early surgical correction constitutes the best treatment. Despite
      recent progresses, mortality remains high but long term results are encouraging.
      The risk factors conditioning prognosis, the surgical options and the question of
      simultaneous coronary bypass will be discussed after a thorough review of the
      literature.

PMID- 11820035
TI  - [Hypothenar hammer syndrome].
AB  - The hypothenar hammer syndrome is an uncommon but underestimated lesion of the
      cubital artery caused by repetitive trauma at the level of the hamate bone. It
      characteristically occurs in patients with a history of manual work as metal
      workers, carpenters and motor mechanics. We present a case of a patient who
      developed this syndrome following intensive use of a dig. Clinical finding,
      diagnosis and treatment are discussed.

PMID- 11820036
TI  - [Dementia in Belgium: prevalence in aged patients consulting in general
      practice].
AB  - Early detection of dementia is an important element for the efficacy of therapies
      currently proposed to slow down disease progression. This detection mainly relies
      on general practitioners. In order to estimate the impact of dementia on health
      services, we have estimated from the data of the NAtional Dementia Economic Study
      (NADES) the prevalence rate of dementia in patients aged > or = 65 years living
      at home and consulting in general practice. The study population was based on the
      sampling of consecutive patients consulting a general practitioner, irrespective
      of the reason and location of the consultation. The diagnosis of dementia was
      based on the CAMDEX performed at home in patients presenting > or = 3 warning
      signs of dementia. The prevalence rate of dementia among 2.234 registered
      patients living at home was 14.3% (CI95: 12.6-16.0). In age groups 65-74, 75-84
      and > or = 85 years, it was 7.0%, 17.5% and 18.5%, respectively, in men, and
      6.1%, 15.8% and 25.2%, respectively, in women. The percentage of demented with
      mild, mild to moderate, moderate and severe dementia was 35.0%, 38.8%, 13.1% and
      13.1%, respectively. After adjusting for the age and sex distribution of the
      Belgian population, the prevalence rate in patients aged > or = 65 years was
      estimated at 11.3%. A diagnosis of dementia had already been made by a specialist
      in 41.5% of patients with dementia, with figures of 19.3%, 34.3%, 41.9% and 60.9%
      according to the severity of disease (mild, mild to moderate, moderate, severe).
      The onset of first symptoms had preceded the diagnosis by an average of 1 year.
      Our results show a high prevalence rate of dementia in the elderly living at home
      consulting in general practice, and less than half of the patients had previously
      been diagnosed. It is possible that a systematic detection will not be performed
      as long as specific treatments are not made widely available.

PMID- 11820037
TI  - [Recommendations for writing patient information statements].
AB  - With Evidence-Based Medicine, shared decision making is attracting considerable
      interest as a means by which patient preferences can be incorporated into
      clinical decisions. Patients cannot express informed preferences unless they are
      given sufficient and appropriate information, including a detailed explanation
      concerning their condition, the different therapeutic options and the likely
      outcomes with and without treatment. A patient education leaflet is a potentially
      powerful tool for communicating information to patients, who will be able to
      participate in the process of decision making. The present article is a review of
      available guides for the writing of patient information materials. It also
      includes criteria for evaluating their quality.

PMID- 11820038
TI  - [Control of cutaneous blood vessels].
AB  - In man, three kinds of sympathetic neurons reach the skin. Some cholinergic
      neurons stimulate the sweat glands, they are excited by temperature-regulating
      centers. Adrenergic neurons release noradrenaline and ATP to reduce cutaneous
      blood flow while cholinergic neurons release acetylcholine and a co-transmitter
      to dilate skin blood vessels. The excitation of both latter types of nerve cells
      depends on influences from temperature-regulating centers, baroreceptors and
      exercise. Moreover, in cutaneous blood vessels, a synthesis of NO is enhanced by
      an increase of body temperature and overall by direct heating of the skin. Burns
      are associated with axon reflexes and release of inflammatory mediators. The
      involvement of these various influences is described.

PMID- 11820039
TI  - [War and medicine in a culture of peace. 2. Synopsis of biological weapons].
AB  - Biological warfare has a long history. Despite the 1972 international convention
      and several attempts at biological weapon eradication, some countries and non
      governmental groups still retain some of these agents. According to their
      potential use, they belong to bioterrorism or to massive destruction weapons. Any
      biological warfare put the civilian medical and paramedical assets at the
      frontline and at high risk for being rapidly contaminated. The prompt recognition
      of a bioterrorist attack and the swift identification of the agent can lead to
      implementation of vaccines, chemoprophylaxis, appropriate treatment and sanitary
      measures.

PMID- 11820040
TI  - [How I explore ... a lichenoid drug reaction].
AB  - Lichenoid drug reactions are specific unwanted cutaneous side-effects related to
      some drugs. The clinical presentation of the lesions often suggests the
      diagnosis, but the distinction with idiopathic lichen planus remains difficult.
      The diagnosis is firmly established by the dermatopathological assessment of a
      cutaneous biopsy. The anamnestic search is focused on drug imputability based on
      well defined criteria. Biologic evaluations and various in vitro tests are little
      contributive and even may prove to be irrelevant.

PMID- 11820041
TI  - [Clinical study of the month. Toxicity of hyperglycemia in intensive care and
      beneficial effects of optimized insulin therapy].
AB  - A large Belgian, prospective, controlled study was performed in 1.548 critically
      ill patients (83% without history of diabetes) hospitalised in a surgical
      intensive care unit. On admission, patients were randomly assigned to receive
      intensive intravenous insulin therapy (maintenance of blood glucose at a level
      between 80 and 110 mg/dl) or conventional treatment (infusion of insulin only if
      the blood glucose level exceeded 215 mg/dl and maintenance of glucose at a level
      between 180 and 200 mg/dl). Intensive insulin therapy reduced morbidity and
      mortality by 40%. These remarkable results should influence further therapeutical
      attitudes in intensive care units and open new perspectives for the management of
      critically ill patients.

PMID- 11820042
TI  - Dental implants: who's responsible for what?.

PMID- 11820043
TI  - Clearance of biofilms from dental unit waterlines through the use of
      hydroperoxide ion-phase transfer catalysts.
AB  - OBJECTIVES: The purpose of this research was to demonstrate the effectiveness of
      hydroperoxide ion-phase transfer catalyst (HPI-PTC) cleaners and disinfectants
      for maintaining dental unit waterlines free of planktonic organisms. METHOD AND
      MATERIALS: Water samples were taken from 117 sites, which included a variety of
      dental units and samples from the sink faucets of most operatories. Samples were
      plated on appropriate bacteriologic media and incubated. The presence or absence
      of biofilms was confirmed by scanning electron microscopy. Twenty-two of the
      dental units were retrofitted with independent water systems; the cleaning
      procedure involved an overnight application of an HPI-PTC cleaner followed by a 2
      minute water rinse. RESULTS: Water from both the air-water syringe and the high
      speed handpiece lines from all untreated units contained at least 6 x 10(2)
      colony-forming units per milliliter of planktonic or free-floating bacteria; the
      average was 1.4 x 10(5) CFU/mL. An initial 5% solution of HPI-PTC successfully
      cleared the lines of any apparent biofilm when applied for 3 consecutive days.
      Thereafter, once weekly use of the cleaner maintained the dental unit water
      supplies free of significant numbers of planktonic organisms. CONCLUSION: Routine
      weekly use of an HPI-PTC cleaner controlled dental unit waterline biofilm and
      reduced, with minimum effort, the microbial contamination level of water used for
      patient treatment to less than 200 CFU/mL.

PMID- 11820044
TI  - Factitial (self-induced) gingival disease: four case reports.
AB  - Bizarre-appearing gingival recessions that do not correspond to any known
      gingival disease or oral manifestation of any known systemic disease are called
      factitial (self-induced) gingival disease. Psychological factors are very
      important in their etiology. Generally, the lesions occur during the time the
      child is experiencing stress associated with the frustration of his or her
      dependency needs. Four cases of self-induced gingival recessions involving
      children aged 4 to 6 years are presented and investigated from the pedodontic,
      periodontologic, and psychiatric viewpoints.

PMID- 11820045
TI  - Effect of potassium nitrate and fluoride on carbamide peroxide bleaching.
AB  - OBJECTIVES: The purpose of this study was to assess the effect on tooth
      sensitivity when potassium nitrate and fluoride were added to a 10% carbamide
      peroxide bleaching gel. METHOD AND MATERIALS: Seventeen maxillary and four
      mandibular arches were bleached using the at-home bleaching technique. The
      bleaching treatment consisted of the simultaneous use of a 10% carbamide peroxide
      gel containing 3% potassium nitrate wt/vol and 0.11 fluoride ion wt/vol on one
      side of the midline and a 10% carbamide peroxide gel only (control) on the other
      side of the midline for 14 nights. A visual analog scale for each side of the
      dental arch was used by the patients to assess tooth sensitivity and tooth
      whitening. Preoperative and postoperative photographs were also taken. RESULTS:
      The addition of potassium nitrate and fluoride significantly decreased the total
      tooth sensitivity reported by the patients. The addition did not significantly
      change the whitening efficacy of the carbamide peroxide bleach. CONCLUSION: A 10%
      carbamide peroxide bleaching gel containing potassium nitrate and fluoride
      produced less tooth sensitivity than did the control bleaching gel during a 2
      week at-home bleaching treatment.

PMID- 11820046
TI  - Pulp-dentin biology in restorative dentistry. Part 5: Clinical management and
      tissue changes associated with wear and trauma.
AB  - Tooth wear occurs during normal mastication. Pathologic wear, including abrasion
      and erosion, may also take place. Formation of reactionary and reparative dentin
      and obturation of dentinal tubules are biologic responses that compensate for the
      loss of tissue. Physical trauma to teeth will affect the blood supply to the
      pulp. Extensive physical trauma may result in the formation of mineralized, often
      bonelike tissue in the pulp chamber. Minor trauma, such as that associated with
      orthodontic tooth movement, may exert transient effects on the pulp or it may
      result in permanent structural changes. No experimental data involving
      restorative work on traumatized teeth have been published, but available evidence
      suggests that special care may be necessary in the restoration of such teeth
      because their reaction patterns may differ from those in nontraumatized teeth.

PMID- 11820047
TI  - An in vitro study of needle force penetration comparing a standard linear
      insertion to the new bidirectional rotation insertion technique.
AB  - OBJECTIVE: The purpose of this study was to determine the effect of a
      bidirectional rotation insertion technique on the force necessary to puncture and
      advance a needle through a tissuelike substance. METHOD AND MATERIALS: Two in
      vitro penetration test models were constructed using different tissuelike
      substances of different densities. Each tissuelike substance was tested with 30
      gauge, 27-gauge, and 25-gauge needles of two brands commonly used in dentistry.
      The needles were placed to a standardized depth of 0.5 inch (1.27 cm) at a
      standardized rate of insertion. A customized dental surveyor allowed controlled
      forces to be applied. A linear insertion technique and a newly described
      bidirectional rotation insertion technique were tested. The force of puncture and
      penetration drag was recorded with an electronic digital scale. A total of 400
      needle insertions were performed. RESULTS: A multivariate analysis of technique,
      material, needle gauge, and needle brand revealed the data to be statistically
      significant, demonstrating no overlap. The post-hoc analysis of between-subject
      effects found that the needle insertion technique accounted for the most powerful
      effect in reducing force penetration. The bidirectional insertion technique had
      the greatest influence on reducing the force penetration irrespective of
      material, needle gauge, or needle brand tested in this study. CONCLUSION: The
      bidirectional rotation insertion technique required two to three times less force
      than did a standard linear insertion technique. A continuous rotation in a single
      direction would be expected to produce similar results. Needle gauge and needle
      design have a smaller effect on reducing force penetration than did the technique
      used during insertion. The in vitro model used in this study represents a
      reliable dynamic testing system that can be used for future evaluation of
      needles.

PMID- 11820048
TI  - Influence of the implant abutment on the Periotest value: an in vivo study.
AB  - OBJECTIVE: Periotest values for dental implants depend on the type of prosthetic
      abutment utilized for the restoration. If Periotest value cannot be measured at
      the single crown, the Periotest values used for comparison must be derived from
      the same type of superstructure. METHOD AND MATERIALS: Fifty-nine patients were
      selected from a regular follow-up program. At the end of the healing period, the
      Periotest values of Frialit-2 implants were measured at the gingiva former and
      abutment. The values were then compared with the Periotest measurements obtained
      at the placement of the final single crown and during the first follow-up
      examination. RESULTS: Compared to values measured at single crowns, the Periotest
      value measured at gingiva formers decreased on average by 3.5. The measurement of
      the abutment revealed a decrease of 1.7. Until the first recall and under
      functional loading of implants, the Periotest value increased on average by 1.8.
      These differences significantly differed from 0. CONCLUSION: If measurements at
      different abutments such as crown abutments or single crowns are necessary,
      comparison of the Periotest values in accordance with the given mean values will
      lead to more precise results. It is recommended that Periotest measurements be
      performed for the first and subsequent prostheses, during all prosthetic stages,
      to allow comparison if some parts of the prosthetic abutment have to be replaced.

PMID- 11820049
TI  - A technique for the removal of restoration overhangs and finishing and polishing
      of restoration and preparation margins.
AB  - Restorations with marginal overhangs are frequently associated with localized
      periodontal defects. Access to overcontoured approximal margins of restorations
      can be difficult to obtain, however. A system featuring a multidirectional
      handpiece is an effective and efficient means of contouring, finishing, and
      polishing restoration surfaces and margins. In particular, the system facilitates
      access to approximal and subgingival areas for the removal of marginal excess and
      overhangs. This system may be a valuable addition to the practitioner's
      armamentarium for operative procedures.

PMID- 11820050
TI  - A practice-based assessment of the handling of a fast-setting polyvinyl siloxane
      impression material used with the dual-arch tray technique.
AB  - OBJECTIVE: The purpose of this study was to assess a new impression material used
      in conjunction with the dual-arch technique. METHOD AND MATERIALS: Ten members
      were selected at random from the Product Research and Evaluation by Practitioners
      (PREP) panel, a United Kingdom-based group of dental practitioners who are
      prepared to undertake research projects in their practices. Explanatory letters,
      a questionnaire, packs of the impression material, and dual-arch trays were
      distributed to the evaluators, together with instructions on the use of the
      materials. The practitioners were asked to use the materials and return the
      questionnaire after using the materials for a minimum of 10 impressions. RESULTS:
      Three evaluators had not previously used the dual-arch technique, six had used it
      in the past or occasionally, and one used the technique routinely. A total of 115
      impressions were recorded with Quick Step. The overall rating for ease of removal
      of impressions from the mouth was 4.7 on a linear scale in which 5 represented
      easy to remove and 1 represented difficult to remove. Four of the evaluators
      rated the working time as excellent and the remaining six as good. Eight of the
      evaluators stated that the quality of fit of the single-unit restoration
      constructed with the combined-arch tray was the same as that obtained when a
      conventional tray technique was used. CONCLUSIONS: The impression material under
      test scored highly for application in circumstances where the fields above and
      below the preparation margin were dry or had limited moisture problems. Eighty
      percent of the evaluators considered the impression and dual-arch tray technique
      to be of benefit to their practice.

PMID- 11820051
TI  - Macromolecular leakage beneath complete cast crowns. A 6-month in vitro
      investigation using microfluorimetry.
AB  - OBJECTIVE: This investigation evaluated the leakage (diffusion) of
      lipopolysaccharide and dextran beneath cast-gold crowns luted with one of three
      cements. METHOD AND MATERIALS: Thirty extracted molars were prepared for crowns.
      Thirty crowns with access ports (facial or lingual) were cast in gold and luted
      to their preparations with zinc phosphate, glass-ionomer, or an adhesive resin
      cement (10 per group). Teeth and crowns with filters inserted in the ports were
      immersed in a solution of labeled macromolecules (tetramethylrhodamine
      isothiocyanate-labeled lipopolysaccharide and fluorescein isothiocyanate-labeled
      dextran) and evaluated for leakage at 2 weeks and 1, 2, 3, 4, 5, and 6 months.
      Filters were retrieved and analyzed with microfluorimetry. RESULTS: No filters
      retrieved from any crowns demonstrated any detectable leakage, and all filters
      were negative for both dextran and lipopolysaccharide for all evaluation periods.
      CONCLUSION: For the 6 months of this investigation, zinc phosphate, glass
      ionomer, and adhesive resin cements were equally effective at preventing leakage
      of detectable molecular concentrations of lipopolysaccharide and dextran to the
      level of the access ports in the absence of thermal or mechanical stress.

PMID- 11820052
TI  - Dental lights, light meters, and light meter readings.

PMID- 11820053
TI  - Progressive facial hemiatrophy (Parry-Romberg syndrome).

PMID- 11820054
TI  - [Complex visual hallucinations in partially sighted elderly: Charles Bonnet
      syndrome].
AB  - In two patients, women aged 85 and 80 years, who suffered from visual
      hallucinations involving living creatures, cars and buildings, Charles Bonnet
      syndrome was diagnosed. Both were worried that these signs were an indication of
      a severe psychiatric condition. In diagnosing the Charles Bonnet syndrome the
      following criteria can be used: presence of complex visual hallucinations,
      retention of insight, absence of hallucinations in other sensory modalities and
      absence of delusions. Hallucinations in dementia, delirium, migraine, epilepsy,
      or in extreme states of exhaustion or sensory deprivation, as well as
      hallucinations due to psychedelic drugs, hallucinations of widowhood and
      hypnagogic and hypnopompic hallucinations must be excluded. Patient education and
      reassurance are the cornerstones of treatment. Other possible treatments are:
      improving visual acuity and the general physical condition, stopping medication
      with hallucinogenic side effects, activating the patient, coaching the patient in
      avoiding hallucination-triggering situations and using stopping strategies, and
      (still experimental) pharmacological treatment with carbamazepine, valproate,
      ondansetron or cisapride.

PMID- 11820055
TI  - [Vulnerability of scientific research in university medical centers].
AB  - In 1995, the Health Research Council of the Netherlands (RGO) published a report
      on the efficiency and efficacy of medical research in the Netherlands. One of its
      conclusions concerned the formation of multidisciplinary research institutes
      around various themes. The medical faculties and university hospitals responded
      by forming integrated university medical centres, which placed a considerable
      emphasis on patient care during their first few years of existence. However, the
      deans of the respective medical faculties realised that these organisational
      changes might form a threat to fundamental research, due to a lack of financial
      resources. They produced a common statement to protect and support fundamental
      research. This was discussed at a meeting of the Royal Netherlands Academy of
      Arts and Sciences in December 2000. Several speakers addressed the question as to
      whether (fundamental) research in these university medical centres should be
      regulated in a 'top-down' manner whereby directions and priorities are formulated
      by a centre's management, or whether the (clinical) researchers should formulate
      the direction of the research ('bottom-up'). Managers wanted a 'top-down'
      approach and researchers a 'bottom-up' approach.

PMID- 11820056
TI  - [Procalcitonin concentrations in the diagnosis of acute inflammatory reactions].
AB  - Procalcitonin is a calcitonin prohormone. During systemic inflammatory response
      it has the characteristics of an acute-phase protein. However, plasma levels rise
      more rapidly than those of the parameter (i.e. C-reactive protein) currently used
      in clinical practice to assess an acute-phase response. The procalcitonin assay
      is easy to perform and results can be available within a short period of time.
      This makes procalcitonin a valuable addition to the current diagnostic work-up
      for acutely ill patients. Procalcitonin can be used as a marker of inflammation,
      to differentiate serious bacterial infections from other generalised inflammatory
      diseases, to differentiate bacterial from viral infections, to differentiate
      infection from disease activity in patients with autoimmune diseases, to
      differentiate infection from rejection in transplant patients, and as a
      prognostic marker in critically ill patients. Procalcitonin may prove to be a
      valuable adjunct in diagnosing and treating patients with a variety of
      inflammatory disorders.

PMID- 11820057
TI  - [Charcot-arthropathy in diabetes mellitus].
AB  - Charcot's arthropathy is a relative uncommon complication of diabetic neuropathy.
      The aetiology remains poorly understood. According to the neurotraumatic theory,
      the foot, which has become insensitive through neuropathy, is subjected to
      extensive (micro)trauma through continuation of use. Ultimately this leads to
      destruction. According to the neurovascular theory, autonomic neuropathy results
      in an increased blood flow in the foot with osteopenia consequently resulting due
      to increased osteoclastic activity and decreased osteoblastic activity. Acute
      Charcot's arthropathy presents with a red, warm, swollen foot, which is usually
      not painful and which eventually becomes ulcerated. An insidious development of
      the condition is also possible. The X-ray of the foot often is normal at
      presentation, but will later show local osteoporosis, erosions, subluxations or
      fractures. Technetium scintigraphy will be abnormal from the beginning, while IgG
      scans are usually normal. The traditional treatment is cast immobilisation with
      careful introduction of protected weight-bearing. After stabilisation,
      orthopaedic footwear is necessary to improve foot function and to prevent
      ulceration. Regular checkups are important.

PMID- 11820058
TI  - [From gene to disease; craniosynostosis syndromes due to FGFR2-mutation].
AB  - One of the genes involved in craniosynostosis syndromes is the fibroblast growth
      factor receptor 2 (FGFR2) gene, a tyrosine kinase receptor gene. Upon ligand
      binding the FGFR2 receptors dimerise, and this is followed by activation of the
      intracellular tyrosine kinase domains. This initiates a cascade of signals that
      influence cell division and differentiation. FGFR2 mutations have been found in
      the Apert, Crouzon and Pfeiffer craniosynostosis syndromes. Most mutations are
      gain of function mutations, inducing ligand-independent receptor activation or
      altered ligand binding. With the exception of Apert syndrome, there is no clear
      genotype-phenotype correlation. Many different mutations have been found in
      Pfeiffer and Crouzon syndrome, but all of the mutations occur in the same
      extracellular region of the receptor. Identical mutations have been found in
      Pfeiffer and Crouzon syndrome. So within one family, both Crouzon and Pfeiffer
      syndrome may occur. Mutations in other FGFR-genes have also been found in
      craniosynostosis syndromes.

PMID- 11820059
TI  - [Diagnostic image (71). A woman with obesity, diabetes mellitus and use of
      corticosteroids. Mediastinal lipomatosis].
AB  - In a 69-year-old obese woman on prednisone treatment for temporal arteritis a
      widened mediastinum on chest X-ray proved to be mediastinal lipomatosis on CT
      scan.

PMID- 11820060
TI  - [Acetylsalicylic acid in primary prevention of cardiovascular events; literature
      study].
AB  - OBJECTIVE: To evaluate literature data on the use of acetylsalicylic acid (ASA)
      as a primary prevention measure for cardiovascular events. DESIGN: Literature
      search. METHOD: Using Medline, all randomised placebo-controlled trials of ASA
      published between 1985 and 1 May 2001, and which used cardiovascular morbidity
      and death as outcome measures were identified (search query: 'aspirin' and
      'primary prevention'). Using the raw data presented in the source publication on
      death, fatal and non-fatal myocardial infarctions and cerebrovascular accidents
      (CVAs), all relative and absolute risk reductions were recalculated with
      confidence intervals. RESULTS: In healthy middle-aged men, men with an increased
      cardiovascular risk profile and persons with diabetes mellitus or hypertension,
      the use of ASA reduces the incidence of myocardial infarction and has a neutral
      effect on cerebrovascular events. The protective effect of ASA seemed most marked
      in those persons with an increased risk of manifest atherosclerotic vascular
      disease. CONCLUSION: Notwithstanding these findings, for each patient it remains
      essential to weigh up the cardiovascular risk profile against the small increased
      risk of complications when prescribing ASA.

PMID- 11820061
TI  - [Meningitis after a superficial dog bite].
AB  - A 63-year-old healthy man developed acute meningitis. A Gram-stain of the
      cerebrospinal fluid showed Gram-negative rods, which grew slowly. They were
      identified by 16S ribosomal RNA sequence-analysis as Capnocytophaga canimorsus,
      an oral commensal found in various animal species including dogs. Upon further
      questioning, the patient mentioned a superficial dog bite. Using fluorescence-in
      situ-hybridisation with specific DNA probes, C. canimorsus cells were detected in
      a gingiva swab from his dog. The strains isolated from the patient and his dog
      were identical. The patient made a quick recovery following therapy with
      cefotaxime. Infections with C. canimorsus are associated with immune suppression
      (especially splenectomy or alcohol abuse), yet 40% of the patients have no
      predisposing conditions. Documented infections concern mainly sepsis or
      meningitis, with a mortality of approximately 30%. Due to its fastidious growth,
      C. canimorsus may be missed in standard culture methods. Therefore, in each case
      of unexplained sepsis or meningitis contact with animals should be enquired
      about.

PMID- 11820062
TI  - [Patient with a lung abscess, primarily treated with drainage followed by
      antibiotics].
AB  - A 45-year-old woman presented herself with coughing, nocturnal sweating, weight
      loss, and chest pain, left laterally. In the previous 5 months she had been
      treated twice with antibiotics due to a suspected pneumonia. With the help of a
      CT scan, 2 subpleural lung abscesses were diagnosed. The primary treatment was CT
      guided drainage, as a result of which the largest abscess was emptied and a
      microbiological diagnosis could be established. Subsequently, the patient made a
      quick recovery with the help of specific antibiotics. It might be better to drain
      lung abscesses, especially subpleural ones, at an early stage rather than wait
      for the results of a trial treatment with antibiotics.

PMID- 11820063
TI  - [Term breech position; an indication for cesarean section].

PMID- 11820064
TI  - [Patient with refractory celiac disease and a secondary lymphoma].

PMID- 11820065
TI  - [Misleading advertisement of Adalat Oros].

PMID- 11820066
TI  - [Misleading advertisement of Adalat Oros].

PMID- 11820067
TI  - [Providing regular relief; considerations for palliative care in the
      Netherlands].

PMID- 11820068
TI  - [Providing regular relief; considerations for palliative care in the
      Netherlands].

PMID- 11820069
TI  - [Female patient with West-Nile fever in the Netherlands].

PMID- 11820070
TI  - Procalcitonin: how a hormone became a marker and mediator of sepsis.
AB  - Calcitonin was discovered in the early 1960s [1], at which time it was assumed to
      be a single hormone with a yet-to-be-determined role in human physiology. Since
      then it has been found to be only one entity among a large array of related
      circulating peptides, at least one of which has a pivotal role in the host
      response to microbial infections [2, 3]. The aim of this review is to describe
      this metamorphosis of an endocrine hormone to a new class of hormokine mediators
      in infectious diseases.

PMID- 11820071
TI  - Graves' ophthalmopathy: natural history and treatment outcomes.
AB  - BACKGROUND: The pathogenesis of Graves' ophthalmopathy has not been yet
      clarified, and from a therapeutic standpoint Graves' ophthalmopathy remains an
      enigma. The natural course and effects of different treatment regimens are poorly
      documented. RESULTS: The mean observation period was 3.23 years (1-8.9 years) for
      all 196 patients, and 2.85 years (1-8.9 years) for the 81 patients with Graves'
      ophthalmopathy. The gender distribution was 77% female and 23% male in patients
      with Graves' disease and ophthalmopathy, and 81% female and 19% male in those
      patients without ophthalmopathy (p = 0.57). Seventy per cent of the patients
      developed Graves' ophthalmopathy within 12 months before or after the onset of
      the hyperthyroidism. Among the 81 patients with ophthalmopathy 53 (65%) received
      no therapy or only local protective agents. Twenty-five of these patients
      improved substantially, 26 did not change, and 2 deteriorated progressively.
      These results were independent of the severity of the EO (p = 0.42). Among the 11
      patients initially treated with systemic corticosteroids 7 improved, 3 did not
      change, and 1 worsened. Five patients received initially orbital irradiation.
      Three improved and 2 did not change after radiotherapy. Orbital decompression was
      performed in 3 patients. Nine patients received a combination treatment.
      CONCLUSION: In conclusion, our study of a relatively large patient sample
      revealed the known epidemiological facts regarding Graves' disease and endocrine
      ophthalmopathy. The majority of patients needed no therapy or only local
      protective agents, and 47% improved spontaneously. Systemic corticosteroids and
      orbital irradiation appear to be equally effective as initial treatment in
      patients with more severe forms of Graves' ophthalmopathy.

PMID- 11820072
TI  - Gender differences in coronary artery size per 100 g of left ventricular mass in
      a population without cardiac disease.
AB  - OBJECTIVES: To determine whether there is a gender difference in coronary artery
      size normalised for left ventricular (LV) mass. BACKGROUND: Small coronary artery
      caliber may play a role as a risk factor for coronary artery disease in women.
      However, the existence of a gender difference in coronary artery size is
      controversial. Furthermore, coronary artery size ought to be normalised for LV
      mass, since there is a theoretical relation of coronary artery size to LV mass
      according to the law of minimum viscous energy loss for the transport of blood in
      the coronary circulation. METHODS: In 200 individuals (100 women) without cardiac
      disease and with normal Doppler echocardiography, left main (LCA) and right
      coronary artery (RCA) size were determined using transoesophageal
      echocardiography. LV mass was assessed by transgastric M-mode echocardiography.
      RESULTS: Age (44 +/- 15 years in women; 41 +/- 16 years in men), the presence of
      non-cardiac diseases, cardiovascular risk factors and medication were similar in
      women and men. LV mass in women was lower than in men (148 +/- 36 g, 189 +/- 45
      g; p < 0.0001). LCA and RCA cross-sectional areas in women were smaller than
      those in men (LCA: 10 +/- 3 and 16 +/- 5 mm2, p < 0.0001; RCA: 4 +/- 2 and 7 +/-
      3 mm2, p < 0.0001, respectively). LCA and RCA cross-sectional areas of women were
      smaller even after normalisation for LV mass (LCA: 7 +/- 3 and 9 +/- 3 mm2/100 g
      LV mass, p < 0.0001; RCA: 3 +/- 1 and 4 +/- 1 mm2/100 g LV mass, p = 0.002,
      respectively). LCA caliber of women ranged below the theoretically expected size
      according to the law of minimum viscous energy loss for the transport of blood in
      the coronary circulation, whereas those of men tended to be above it.
      CONCLUSIONS: In a population without cardiac disease, women have smaller coronary
      artery size even after normalisation for left ventricular mass.

PMID- 11820073
TI  - Lethal ingestion of stored Amanita phalloides mushrooms.
AB  - We report the first case of a lethal Amanita phalloides intoxication from stored
      mushrooms. After picking the mushrooms were kept in a freezer for 7-8 months.
      This case is in accordance with the well-known stability of the amatoxins and
      demonstrates the possibility of A. phalloides poisoning at any time of year.

PMID- 11820074
TI  - [Medical emergencies in dental practice in Switzerland].

PMID- 11820075
TI  - [Profilometric determination of substance removal and surface morphology after
      microabrasion in vivo].

PMID- 11820076
TI  - Operational feasibility and efficacy of deltamethrin impregnated hessian curtains
      in comparison to HCH indoor residual spraying to control malaria in selected
      villages of District Ghaziabad (U.P.), India.
AB  - A study was carried out in selected villages of District Ghaziabad to evaluate
      the operational feasibility and efficacy of hessian curtains impregnated with
      deltamethrin@100 mg/m2 in comparison to indoor residual spraying of HCH@0.2 g/m2.
      The impregnation was carried out before onset of transmission and observations
      were continued up to two transmission periods. District Health Authorities have
      carried out HCH indoor residual spraying (IRS) as per schedule in the control
      village. Entomological evaluation revealed 87 per cent reduction of An.
      culicifacies up to six months in comparison to HCH indoor residual spraying.
      However, the reduction in densities of total mosquitoes was only 61.6 per cent.
      Follow-up studies revealed that the impact of deltamethrin impregnated curtains
      was diluted after 6-7 months. The results of bioassay tests revealed 100 per cent
      mortality up to 6-7 months. Epidemiological evaluation revealed 81.9 per cent
      reduction in total malaria cases as against 88.5 per cent with P. falciparum
      cases. Similar reduction was also observed when slide positivity rate (SPR),
      slide falciparum rate (SfR), cases/000 and Pf/000 were compared to corresponding
      village. Pilot studies are indicated to evaluate the relative efficacy of
      impregnated curtains, which is quite cheaper than conventional residual
      insecticide spraying (IRS).

PMID- 11820077
TI  - Malaria during pregnancy and its effects on foetus in a tribal area of Koraput
      District, Orissa.
AB  - Malaria during pregnancy and its maternal and foetal complications was studied in
      Koraput district of Orissa--a tribal area, endemic for malaria. A total of 209
      pregnant women with 738 pregnancy months were studied. The parasitic index among
      the pregnant women ranged between 10.8 and 25.6 per cent with peak incidence
      during post-monsoon months. There was a significant difference in parasite
      incidence between the primi- and multigravidae (p < 0.05) but difference was not
      observed between the trimesters. The mean haemoglobin (Hb) concentration declined
      to 8.4 g/dl (range 7.2-10.2 g/dl) at full-term and parturition from its initial
      level of 9.6 g/dl (range 7.2-12.8 g/dl). There was a significant difference (p <
      0.05) in Hb concentration among the trimesters of pregnancy. There was no
      significant difference in the outcome of pregnancies in women with or without
      malaria prarasites in their peripheral blood. There was no significant difference
      in Hb concentrations between malaria parasite positive and negative pregnant
      women (p > 0.05). Significant difference was observed in the proportion of
      newborn positives from mothers with or without malaria parasites indicating a
      high degree of transplacental transmission. The overall foetal mortality rate was
      21.5 per cent. The miscarriage, stillbirth, premature delivery leading to foetal
      and neonatal along with perinatal mortality constituted for 24.4, 13.3, 20 and
      17.7 per cent of all mortalities respectively.

PMID- 11820078
TI  - Effect of plant spacing on the population of mosquito immatures in rice fields in
      Madurai, south India.
AB  - A study was conducted during 'Kuruvai' crop season from December 1992 to January
      1993 in the rice fields of the Agricultural College and Research Institute,
      Madurai, Tamil Nadu to determine the influence of plant spacing and plant canopy
      on the populations of mosquito immatures. Three paddy varieties (ADT36, IR50 and
      IR20) were selected with two types of plant spacing, one with normal spacing (15
      x 10 cm) and another wider (20 x 15 cm) than the normal spacing. Results showed
      that the field planted with normal spacing of paddy had significantly higher
      populations of culicine and anopheline immatures than the fields planted with
      wider spacing of paddy. The paddy varieties did not have any significant effect
      on the population of mosquito immatures. Light intensity, measured at the water
      surface using an illuminometer, was inversely related to the development of plant
      canopy and the results suggested that plant canopy does not inhibit oviposition
      by mosquitoes in the early stages of paddy growth, but it was responsible for the
      decline in the populations in the later stages of paddy growth. The plant spacing
      had a significant effect on the populations of chironomids and libellulids and
      other insects were not affected significantly.

PMID- 11820079
TI  - Tumor necrosis factor-alpha in patients with malaria.
AB  - Serum concentration of Tumor Necrosis Factor-alpha (TNF-alpha) was observed in 54
      parasitologically confirmed cases of malaria. Of them, 15 cases were Plasmodium
      falciparum with cerebral involvement, three cases with mixed infections of P.
      falciparum and P. vivax, 32 cases of P. vivax, three cases of P. malariae and one
      case of P. ovale. Five out of 15 patients of P. falciparum (33.3 per cent), one
      out of 54 patients with mixed infection of P. falciparum and P. malariae (1.8 per
      cent) and the sole case of P. ovale (1.8 per cent) had fatal outcome. The serum
      TNF-alpha measured by avidin-biotin sandwich ELISA, was found to be significantly
      raised in P. falciparum and more so in fatal infections. The degree of
      parasitaemia, due to single or double infection, had positive effect on cytokine
      production. The mean TNF-alpha concentration was statistically significantly
      higher (p < 0.001) in P. falciparum than in P. vivax parasites infection. The
      mean TNF-alpha values in P. falciparum and P. vivax were 915 and 280.6 against
      the values in normal healthy controls of 12.9 pcg/ml respectively (p < 0.001).
      The study thus showed that the serum concentration of TNF-alpha correlated well
      with severity of malaria and these values could be used as an important
      prognostic marker of the disease.

PMID- 11820080
TI  - Prevalence and association of sickle-cell haemoglobin and P. falciparum infection
      among tribals in Koraput District, Orissa State.

PMID- 11820081
TI  - Chloroquine resistant Plasmodium falciparum in migrant population.

PMID- 11820082
TI  - Insecticide susceptibility status of Anopheles stephensi (Liston) in Calcutta,
      West Bengal.

PMID- 11820083
TI  - Cerebellar ataxia in falciparum malaria--a report of two cases.

PMID- 11820084
TI  - Control of Aedes breeding using bactoculicide and neem oil combination in
      evaporation coolers.

PMID- 11820085
TI  - An outbreak of malaria in a village in Faridabad district, Haryana.

PMID- 11820086
TI  - Occupational malaria and health risk among select occupational health care
      employee groups in an urban hospital at Tirupati, A.P.
AB  - Epidemiological studies on occupational environments are very meagre in the
      developing countries like India. For this reason an attempt was made in the
      present investigation to see the occupational risk of malaria among health care
      workers of Sri Venkateswara Ramnarayan Ruia Government General Hospital
      (SVRRGGH), Tirupati, Andhra Pradesh. The cohort studies revealed association
      between exposure to occupational (hospital) environment and malaria among
      hospital staff. Retrospective cohort studies were made. 1,454 subjects namely
      hospital staff exposed to occupational environment included civil assistant
      surgeons and physicians, the students of medicine, the students of nursing,
      permanent nursing staff and the class IV employees (class IV included janitorial,
      male nursing orderlies, female nursing orderlies, attenders, laundry workers and
      the rest). Retrospective epidemiological studies were carried out for four years
      on the cohorts and the hospital staff. The data showed statistically significant
      relative risk and attributable risk for malaria. Physicians and civil assistant
      surgeons showed no incidence of malaria. The relative risk for malaria in the
      class IV employees was 1.27, 0, 5.8 and 2.9 for the years 1995-98. The students
      of nursing showed 4.2, 2.42, 3.3 and 0 relative risk for malaria, whereas the
      students of medicine showed 2, 2, 2 and 1.6 for the years 1995 to 1998. The
      attributable risk was ranged from 21.76-82.70, 58.75-76.17, 50-80 for the class
      IV employees, the students of nursing and the students of medicine
      retrospectively. These results provide an evidence for an association between
      occupational environment and malaria for the hospital staff and is more prevalent
      among certain groups of the hospital staff.

PMID- 11820087
TI  - Prognostic implication of hypocalcemia and QTc interval in malaria.
AB  - Hundred confirmed cases of malaria were included in the present study to
      determine the clinical and prognostic implications of hypocalcemia and corrected
      QT interval (QTc) prolongation in malaria. Peripheral blood smear examination was
      done to determine the parasite species and the parasite load. Serum calcium level
      and QTc measurements in electrocardiogram were done for each patient. Fifty
      patients were of P. falciparum malaria (38 complicated and 12 uncomplicated), 40
      of vivax malaria and 10 patients were having mixed (P. falciparum and P. vivax)
      infection. Hypocalcemia was found in 26 cases in which QTc was prolonged. Ten
      patients who had convulsions, all of them were having QTc prolongation and eight
      had hypocalcemia. A total number of eight patients had muscle spasm, of which six
      had QTc prolongation and four had hypocalcemia. There were 34 cases of cerebral
      malaria, of which 18 had hypocalcemia as well as QTc prolongation, 12 of them
      developed renal failure and 14 had high parasitaemia. Four patients died who had
      hypocalcemia and QTc prolongation due to hepatorenal syndrome. The mean parasite
      load, QTc interval and serum calcium were 2.69 +/- 1.0, 0.468 +/- 0.055 sec and
      8.16 +/- 0.86 mg/dl respectively in complicated falciparum malaria; 1.6 +/- 0.55,
      0.442 +/- 0.043 sec and 8.72 +/- 0.97 mg/dl in complicated mixed (Pf + Pv)
      infection. 1.33 +/- 0.52, 0.435 +/- 0.035 sec and 9.77 +/- 1.34 mg/dl in
      uncomplicated falciparum malaria and 1.35 +/- 0.58, 0.403 +/- 0.019 sec and 9.68
      +/- 0.99 mg/dl in vivax malaria. The difference was significant between
      complicated falciparum and mixed (Pf + Pv) infection when compared to
      uncomplicated falciparum and vivax malaria (p < 0.05).

PMID- 11820088
TI  - Splenomegaly in school children in a remote tribal area of Dhole district,
      Maharashtra.
AB  - Sickle-cell gene is known to protect against P. falciparum infection and provides
      a selective survival advantage in those areas where P. falciparum infection is
      endemic. This protection is not absolute and many other factors, inherited and
      acquired also contribute to the immunity against P. falciparum infection. We
      investigated incidence of splenomegaly and typical history of malaria in the past
      two years in apparently healthy school children in a tribal area in Dhole
      district of Maharashtra to see whether the incidence of malaria (splenomegaly and
      typical history) was different in children having sickle-cell trait to that of
      those who did not have this trait. A total of 480 school children were clinically
      examined for splenomegaly and history of typical malaria fever and/or blood slide
      positivity for malaria in the past two years. About 9.55 per cent of normal
      population had either splenomegaly or convincing history of malarial infection in
      the past two years which is not statistically different from the sickle-cell
      trait patients having evidence of past malaria (8.79 per cent; p > 0.05).

PMID- 11820089
TI  - Mosquito fauna and malaria vectors in Jairampur, district Changlang, Arunachal
      Pradesh.
AB  - In an entomological study, covering three biotopes like village, panikheti (wet
      rice cultivated land) and urban agglomeration, a total of 35 species of
      mosquitoes in eight genera were recorded in Jairampur area of Arunachal Pradesh.
      Two mosquito species--Orthopodomyia anopheloides and Tripteroides indicus were
      recorded for the first time in Arunachal Pradesh. Anopheles dirus and An.
      minimus, the two well-known malaria vectors were encountered in the study along
      with several potential vector species like An. annularis, An. culicifacies, An.
      maculatus group and An. philippinensis/nivipes. The diversity of mosquito species
      as well as the man-vector contact was maximum in the panikheti and minimum in the
      village biotope.

PMID- 11820090
TI  - Estimating parasite density in patients suffering from falciparum malaria in an
      endemic area in Kolkata.
AB  - Parasite density of one hundred patients suffering from falciparum malaria in an
      endemic area in Kolkata was determined using three different methods. In the
      first of these, parasite density per microlitre of blood in a patient was
      determined using parasite count adjusted by average WBC count (i.e.
      8000/microliter) observed in microscopic fields of the thick film. In the
      remaining two methods, only raw (i.e. unadjusted) parasite counts in microscopic
      fields of the same slide were used. A statistical analysis was carried out in
      detail to compare these methods based on raw and adjusted parasite counts and
      also to find out a suitable method which can be used in practice. Estimating the
      density of parasites is of primary importance in determining the severity of
      infection. Furthermore, parasite density can help in identifying short-treatment
      and long-treatment failure vis-a-vis detection of development of resistance in P.
      falciparum against the drug used. This article reports some findings that
      indicate the existence of a potentially dangerous situation in the study area.

PMID- 11820091
TI  - Entomological and epidemiological studies on malaria in Rajmahal range, Bihar.
AB  - The epidemiological investigations carried out in six tribal villages in Rajmahal
      range hill in south Bihar revealed average slide positivity rate (SPR) 25.1
      ranging between 9.8 and 37.8 per cent. Plasmodium falciparum was the dominant
      parasite which accounted 64.2 per cent of the total infections. Results of mass
      blood survey indicated the presence of high percentage of asymptomatic carriers
      of malaria parasites in the local populace. In an entomological survey, 25
      species of mosquitoes under five genera were collected in 20 trap nights. The
      average density of mosquitoes recorded was 230.6 per trap night. Anopheles
      mosquitoes alone accounted 72.8 per cent of the total collection whereas malaria
      vectors Anopheles maculatus, An. minimus, An. philippinensis, An. varuna and An.
      annularis accounted 32.8 per cent of the total anophelines collected. Both
      anopheline and culicine mosquitoes were found susceptible to DDT (4 per cent) and
      malathion (5 per cent) in 30 min exposure. Dissection of malaria vectors An.
      minimus, An. maculatus and An. philippinensis revealed very high percentage of
      parity rate (77.8 per cent) which gives a strong indication about their vectorial
      status in the transmission of malaria. Poor socio-economic condition, lack of
      sense of hygiene worsen the situation in the presence of asymptomatic carriers.

PMID- 11820092
TI  - Preliminary observations on man-mosquito contact in Soraipung village of district
      Dibrugarh, Assam (India).

PMID- 11820093
TI  - Nutritional and sensory evaluation of tempe-fortified maize-based weaning foods.
AB  - Maize-based weaning foods prepared from whole maize meal or dehydrated fermented
      maize (ogi) flour fortified with soybean, cowpea or groundbean tempe, with or
      without the addition of melon seed flour were fed to 40 albino weanling rats. The
      nutrient quality of the weaning foods was monitored by the measurement of protein
      efficiency ratio (PER), net protein ratio (NPR), true digestibility (TD),
      biological value (BV) and net protein utilization (NPU). Amino acid composition
      and amino acid scores were determined. The weaning foods were also evaluated for
      sensory properties and acceptability by nursing mothers and their children.
      Protein efficiency ratio, net protein retention and net protein utilization of
      the fortified weaning foods were not significantly different (P > 0.05) when
      compared to casein diet (control). True digestibility of tempe-fortified maize
      based weaning foods averaged 85.4 +/- 3.4% compared to 94.4%, for casein diet.
      Results from sensory analysis showed that relative to tempe-fortified maize-based
      weaning foods, most mothers preferred Cerelac, a commercial weaning food, and its
      porridge because of its vanillic flavour and sweet taste. Despite the low scores
      recorded for aroma and taste of tempe-fortified maize-based weaning foods, most
      mothers and their children found porridges prepared from these foods acceptable,
      with a preference for ogi fortified with cowpea tempe. Tempe-fortified maize
      based weaning foods had high protein quality and can support the growth of
      infants in developing countries especially during the critical weaning period (6
      12 months). They were comparable to Cerelac, a commercial baby food in colour and
      texture.

PMID- 11820094
TI  - Effect of exogenous histidine and Garcinia cambogia on histamine formation in
      skipjack (Katsuwonus pelamis) homogenates.
AB  - Histamine consumed with food gives rise to allergic reactions. Dark muscle fish,
      for example skipjack (Katsuwonus pelamis) has been shown to contain histamine.
      Studies using TLC (acetone: NH4OH, 80:20.5) on silica gel G60 plates and
      densitometry after spraying with ninhydrin, using a computerized densitometer,
      showed that freshly harvested skipjack has no detectable histamine (detection
      limit, 50 micrograms.g-1 fish). However, with time histamine (Rf 0.84) is formed
      > 1.5 mg.g-1 probably through microbial action. Skipjack contains high levels of
      free histidine at levels of > 10 mg.g-1 (Rf 0.41) but fish like seer
      (Scomberamous spp.), which are not reported to be allergenic, contain < 4 mg.g-1
      histidine. Addition of exogenous histidine (50 mg.g-1) results in histamine
      formation in seer 2.2-fold that of skipjack under the same conditions. A type of
      herring (Amblygaster spp., sinhala-hurulla) is not a histamine former, but had
      been shown to cause allergenic reactions, resulting in a ninhydrin positive spot
      (Rf 0.79) on incubating for 24 hours. Addition of arginine and lysine to blended
      skipjack results in their loss probably by decarboxylation. Addition of the spice
      Garcinia cambogia (extracts 0.2 g ml-1) known as 'goraka' in Sri Lanka (sinhala)
      and 'kukum' in India (hindhi), to fresh skipjack incubates prevents histamine
      formation as a results of lowering pH to 3.2-3.6 whereas Avverhoea bilimbi
      (bilin) and Tamarindus indica (tamarind) extracts did not prevent histamine
      formation.

PMID- 11820095
TI  - Plasma, liver and kidney folate and plasma homocysteine concentrations are poor
      response variables at very low dietary folate intakes, in a folate
      depletion/repletion rat model.
AB  - Folate depletion/repletion rat models are popular protocols for assessing the
      bioavailability of folate. Much of the early work carried out on folate
      bioavailability concentrated on foods naturally high in folate. However, foods
      low in folate often contribute significantly to folate intake because of their
      high consumption in the general population. Therefore, the assessment of the
      bioavailability of foods low in folate is essential to properly estimate folate
      intake. The present study investigated plasma, liver and kidney folate and plasma
      homocysteine concentrations as appropriate response variables for measuring
      folate bioavailability in the rat at very low dietary folate intakes. One hundred
      and one weanling male rats (Wistar strain) were fed a folate-deficient diet
      containing 1% succinyl sulfathiazole for 28 d. Following depletion, six rats were
      randomly assigned to each of 16 repletion diets containing folic acid, fortified
      white bread, unfortified wholemeal bread or unfortified rye bread calculated to
      provide 6.25, 12.5, 18.75 and 25 micrograms folate/kg of each diet. After a
      further 28 d, plasma, liver and kidney folate concentrations were determined by
      microbiological assay. Plasma homocysteine was measured by HPLC as a functional
      indicator of folate status. Only a weak correlation was found between the
      response variables measured and dietary folate intake, indicating that this
      folate depletion/repletion rat model is not suitable for testing the response of
      rats fed diets containing very low levels of folate.

PMID- 11820096
TI  - Physical characteristics of modified milkfat in high-melting fat preparation.
AB  - Anhydrous milkfat (AMF) was fractionated to obtain a series of high-melting
      milkfat fractions (HMF). Solid fat content (SFC) of HMF as determined by nuclear
      magnetic resonance (NMR) was in the range 37.6-43.6% and 21.2-27.5% measured at
      20 and 30 degrees C, respectively. The HMF have a higher melting characteristic
      compared to AMF as analyzed by differential scanning calorimetry (DSC) with
      melting enthalpies of 92.2-105.0 J/g and melting peak temperatures of 39.3-41.5
      degrees C. The AMF was also blended with soft palm stearin (SPOs and/or hard palm
      stearin (HPOs)) according to a three conventional component mixture design which
      providing suitable formulations for HMF. This represented three selected blends
      of AMF:SPOs:HPOs at three different proportions (70:15:15, 60:30:10 and 50:45:5),
      having SFC and DSC melting characteristics of HMF. The study revealed that higher
      melting characteristics of AMF could be achieved equally well by using both
      fractionation and blending techniques.

PMID- 11820097
TI  - Effect of salts on the functional properties of benniseed (Sesamum radiatum) seed
      flour.
AB  - The effects of salts, KCl, NaCl, K2SO4, Na2SO4 and CH3COONa on the functional
      properties of benniseed (Sesamum radiatum) flour were studied. Results showed
      that the lowest gelation concentration of 18% observed in the absence of the
      salts was improved and found between 12 and 16% in the presence of different
      salts under consideration. The foaming capacity of about 18.0% in distilled water
      increased progressively from 30.5 +/- 1.0 to 56.0 +/- 0.6% depending on the
      concentrations and types of salts used. At low salts concentrations (0.5, 1.0 and
      2.0%) the water absorption capacity decreased between 89.8 +/- 0.5 and 85.0 +/-
      0.6% comparably with 182.0% in the absence of salts while the emulsion capacity
      also decreased between 43.5 +/- 0.2 and 42.0 +/- 0.9% with increase in salt
      concentrations of 0.5 to 10.0%. The foaming capacity and foaming stability that
      were 18.0 and 3.0% in the absence of the salts were improved and found within the
      range of 30.5 +/- 1.0 to 56.0 +/- 0.1% and 14.0 +/- 0.8 to 22.4 +/- 0.1%
      respectively. The dependence of protein solubility with pH was found to be a
      function of the type and concentration of salts considered. The curves showed
      that the solubility of the protein of the flour was found between the pH of 5.0
      in the absence of the salt and varied between pH of 2.5 and 7.5 indicating that
      the protein is soluble in both the acidic and basic regions of pH scale. At high
      concentration of 5.0 and 10.0% of all the salts used, the solubility was
      high/enhanced at acidic region of pH, suggesting that the protein may be useful
      in acid food formulations.

PMID- 11820098
TI  - Factors associated with caffeine consumption.
AB  - The main aim of this research was to identify factors that were related to
      caffeine consumption. From this investigation it can be concluded that coffee is
      the main source of caffeine and that consumption varies with time of day.
      Individuals may be utilising the arousing effects of caffeine by consuming it at
      times when arousal is low for instance to counteract sleep inertia or a post
      lunch dip in alertness. There is, however, very little evidence to suggest that
      psychological characteristics such as personality traits or psychosocial factors
      are important in influencing caffeine consumption, although smoking was found to
      be related to the amount of caffeine consumed.

PMID- 11820099
TI  - Homestyle quick-cooking rice meal products.
AB  - The study developed processes for quick-cooking rice meal products (QCRMP) paella
      and bringhe originally based on homestyle recipes. These QCRMPs consisted of
      basal quick-cooking waxy Malagkit Sungsong and non-waxy irrigated rice (IR) 42
      Philippine rice cultivars, dehydrated vegetables, textured vegetable proteins
      (TVPs) as meat analogs, and seasonings. The rehydrated QCRMP paella and bringhe
      were found to be more acceptable than their conventionally prepared counterparts
      at 5% level of significance based on results of sensory acceptability evaluation
      by 50 consumer panelists. Improvement of the sensory attributes of the QCRMPs was
      ascribed to the use of alternate concentrates and powdered ingredients which
      imparted more intense flavors to the developed products than their fresh
      counterparts.

PMID- 11820100
TI  - Breakfast quality differences among children and adolescents in Croatia.
AB  - The aim of this study was to establish nutrient intake from breakfast in children
      and adolescents in Croatia (n = 1190). A quantified FFQ method was used. The
      results showed that 1.7% of subjects skip breakfast. Energy intake from breakfast
      was 26% RDA. Adolescents obtained significantly more energy from carbohydrates
      and less from fat than children. Children had significantly higher cholesterol
      and significantly lower dietary fiber intake than adolescents. Intakes of almost
      all examined micronutrients differed significantly according to age. Milk and
      dairy products were major energy contributors in children's breakfast whereas
      most of the adolescents' energy came from cereal products. Breakfasts containing
      at least one dairy food, one cereal food and fruit/fruit juice were consumed by
      13.7% and 21.9% of children and adolescents respectively. A total of 33.3% and
      47.6% of subjects respectively consumed milk every day while 15.9% and 10.4% did
      not consume milk for breakfast at all. Subjects with BMI > 85th percentile had
      significantly higher energy intake while those with BMI < 25th percentile had
      significantly lower energy intake than those of normal weight. Education about
      adequate nutrition and human health and providing breakfast at schools would
      improve dietary habits of this population.

PMID- 11820101
TI  - [Diagnosis in Babylon and Assyria].

PMID- 11820102
TI  - [On the knife's incision. Patient perspectives regarding the surgical practice of
      Lorenz Heister (1683-1758)].

PMID- 11820103
TI  - [In the "invisible vise": the secret documents of the geneticist Nikolaj V.
      Timofeeff-Ressovsky].

PMID- 11820104
TI  - [The equality and the future for work in the field of health].

PMID- 11820105
TI  - Developing regional workplace health and hazard surveillance in the Americas.
AB  - An objective of the Workers' Health Program at the Pan American Health
      Organization (PAHO) is to strengthen surveillance in workers' health in the
      Region of the Americas in order to implement prevention and control strategies.
      To date, four phases of projects have been organized to develop multinational
      workplace health and hazard surveillance in the Region. Phase 1 was a workshop
      held in 1999 in Washington, D.C., for the purpose of developing a methodology for
      identifying and prioritizing the top three occupational sentinel health events to
      be incorporated into the surveillance systems in the Region. Three surveillance
      protocols were developed, one each for fatal occupational injuries, pesticide
      poisoning, and low back pain, which were identified in the workshop as the most
      important occupational health problems. Phase 2 comprised projects to disseminate
      the findings and recommendations of the Washington Workshop, including
      publications, pilot projects, software development, electronic communication, and
      meetings. Phase 3 was a sub-regional meeting in 2000 in Rosario, Argentina, to
      follow up on the progress in carrying out the recommendations of the Washington
      workshop and to create a Virtual Regional Center for Latin America that could
      coordinate the efforts of member countries. Currently phase 4 includes a number
      of projects to achieve the objectives of this Center, such as pilot projects,
      capacity building, editing a compact disk, analyzing legal systems and
      intervention strategies, software training, and developing an internet course on
      surveillance. By documenting the joint efforts made to initiate and develop
      Regional multinational surveillance of occupational injuries and diseases in the
      Americas, this paper aims to provide experience and guidance for others wishing
      to initiate and develop regional multinational surveillance for other diseases or
      in other regions.

PMID- 11820106
TI  - [Low impact of silent hepatitis B virus infection on the incidence of post
      transfusion hepatitis in Venezuela].
AB  - OBJECTIVE: Silent infection by hepatitis B virus (HBV) occurs in the absence of
      serological markers for the virus. This type of occult infection is generally
      chronic, asymptomatic, and associated with low levels of viral replication. This
      study determined the presence of HBV DNA in the sera of blood donors who were
      negative for serological markers that were tested during screening, with the goal
      of evaluating the impact of silent HBV infection in posttransfusion hepatitis B
      in Venezuela. METHODS: A total of 2,075 sera were tested in 53 serum pools of 25
      50 donations (0.5-1.0 mL from each sample). The pools were subjected to
      ultracentrifugation prior to DNA extraction by the proteinase K,
      phenol/chloroform method. RESULTS: No HBV DNA was found in any of the pools by
      nested polymerase chain reaction, using primers for highly conserved regions of
      the genes that code for the surface antigen and for the viral capsid.
      Aminotransferase levels were normal in 98% of 200 sera that were tested.
      CONCLUSIONS: These results suggest that there is a low risk of acquiring
      posttransfusion hepatitis B in Venezuela.

PMID- 11820107
TI  - [Prevalence of and factors associated with hepatitis B virus markers in a rural
      population of central Brazil].
AB  - OBJECTIVE: To carry out a survey of hepatitis B virus seroepidemiology in a
      municipality in central Brazil, on the border of two large ecosystems, the
      cerrado (savanna) and the Amazon River basin. METHODS: The municipality studied,
      Nova Mutum, is located in the north central portion of the Brazilian state of
      Mato Grosso. The study sample of 754 individuals included persons from families,
      selected at random, who were living in the municipality's urban center as well as
      all the individuals living in a nearby rural village. Ages ranged from 2 to 79
      years. All eligible individuals were interviewed. Blood was collected and used to
      assess hepatitis B virus markers by enzyme-linked immunosorbent assay. RESULTS:
      Hepatitis B virus infection was found in 232 individuals, or 31% of them; 19 of
      them (3%) were HBsAg-positive. Of the 754 persons, 149 of them (20%) who reported
      having been vaccinated against hepatitis B and who presented anti-HBs positivity
      were classified as vaccine responders. With the multivariate analysis, the
      variables found to be associated with exposure to hepatitis B virus were having
      begun sexual relations, having been vaccinated against yellow fever with a needle
      free jet injection gun (for the age group < 20 years), and being an immigrant
      from southern Brazil (> 20 years). Vaccine coverage was low among individuals
      older than 10 years. The largest share of susceptible individuals (74%) were
      found in the age group of 11 to 20 years. CONCLUSIONS: Our data suggest that
      hepatitis B virus vaccine coverage in Brazil should be extended to include
      teenagers in populations that have a low to moderate hepatitis B virus
      prevalence. It is likely that our results can be extrapolated to other areas of
      Latin America with a similar epidemiological pattern.

PMID- 11820108
TI  - The traditional and conventional medical treatment of cutaneous leishmaniasis in
      rural Ecuador.
AB  - OBJECTIVE: To explore the knowledge, beliefs, and practices (KBPs) regarding
      cutaneous leishmaniasis (CL) treatment held by an endemic population in Ecuador.
      METHODS: A follow-up to research done several years before, this study used
      random cluster sampling to select 529 adults who lived in rural northwestern
      Ecuador. Data were collected over a 24-month period using in-depth interviews
      supplemented with qualitative methods. RESULTS: Most of the subjects were
      familiar with CL. The interviewed persons described a large, diverse ethnomedical
      treatment inventory. Contrary to expectations, few treatment KBPs were predicted
      by gender, age, or prior CL experience. Factors reported as important in
      treatment decisions included female reproductive status, CL "type" (perceived
      form of the illness), lesion location, number of other infected household
      members, cost of the various treatments, treatment availability, and perceived
      treatment effectiveness. Subjects' strong motivation for prompt treatment
      appeared to be associated with beliefs regarding the inability of CL lesions to
      heal spontaneously, the disease's propensity to progress into fatal illnesses,
      and disfigurement. Despite increased familiarity with Glucantime (meglumine
      antimonate), the conventional pentavalent antimonial drug used to treat CL in
      Ecuador, the proportion of subjects who had used it in their treatment remained
      low (20%) while the prevalence of premature drug discontinuance appeared to have
      doubled in comparison to our earlier study. CONCLUSIONS: By itself, increased
      access to Glucantime is unlikely to increase usage of the drug and to reduce its
      frequent premature discontinuance unless public health planners accommodate the
      health and illness world views of local populations. Efficacy and safety studies
      should be undertaken to investigate promising traditional remedies as possible
      alternatives to Glucantime.

PMID- 11820109
TI  - [Ongoing health management control by cost monitoring through tracer indicators].
AB  - OBJECTIVE: To determine the operational cost of a hospital's surgical unit,
      compare those results with standards, and determine the incidence of the costs;
      to produce an effective methodology for this purpose that can be applied to all
      kinds of medical units using any low-cost widely available computer database
      system, with that methodology being utilized for ongoing management control.
      METHODS: This study was carried out in 1999 in the Orthopedics and Traumatology
      Unit of the "Domingo Funes" Public Hospital, in the province of Cordoba,
      Argentina. Of the 817 patients who underwent diagnostic or therapeutic procedures
      in that unit during the year, we selected the 154 of them who were hospitalized
      and required surgical or instrumental procedures. The study used the tracer event
      method described by Kessner. Through a consensus process, medical specialists and
      health economists selected and defined these indicators, which were categorized
      in relation to their complexity (high, medium, limited, or none). Direct and
      indirect costs were assessed in order to study their contribution to total cost.
      Total cost was estimated using nine variables that were applied to the different
      tracer events. RESULTS: The largest portion of total cost, both real and
      standard, was based on the "bed-day" variable. Of this bed-day cost for all
      tracer events, 51.2% was due to an indirect cost of "social hospitalization"
      (keeping patients hospitalized for such reasons as transportation difficulties or
      delays in receiving requested medical supplies) and 48.8% to a direct cost of
      true therapeutic hospitalization. This bed-day cost was 117% higher for the real
      costs as compared to the standard costs. The indirect costs of social
      hospitalization and of therapeutic supplies made up nearly half of the total real
      cost. Excluding the indirect costs, the real cost of all the tracer events
      exceeded the standard cost by only 6.4%. Including the indirect costs of social
      hospitalization and of therapeutic supplies, the real cost exceeded the standard
      cost by 39.8%. The amount spent on medical staff and support personnel
      represented just 11.5% of the total cost. DISCUSSION: Suggestions are provided in
      various areas, including solutions for the high cost of social hospitalization
      and therapeutic supplies, the cost-control benefits of creating protocols for
      procedures and treatments, and the rational utilization of technology in order to
      improve efficiency and reduce risks. The wider application of this procedure is
      recommended for cost-management control in all hospital units carrying out
      surgery or other medical procedures.

PMID- 11820110
TI  - [Lack of food and nutritional security in Central America: contributing factors
      and social exclusion].
AB  - In August 2001, the XVII Meeting of the Health Sector in Central America and the
      Dominican Republic (RESSCAD) was held in Managua, Nicaragua. At the meeting, a
      resolution was adopted in support of strengthening and furthering the Central
      American initiative for the Promotion of Food and Nutritional Security. This
      paper examines the conceptual framework behind the initiative, which was approved
      by the XIV Central American Presidents Summit Meeting (Guatemala City, Guatemala)
      and launched in 1994 at the regional, national, and municipal levels (Guacimo,
      Costa Rica, 1994). It focuses on the accomplishments attributable to this
      initiative, the challenges it has faced over 2001 and those it will be facing
      over the next biennium, and the measures taken or recommended so far in order to
      ensure its long-term success.

PMID- 11820111
TI  - Beware of payment schemes and bad advice.

PMID- 11820112
TI  - Are we prepared?

PMID- 11820113
TI  - Pharma-lary.

PMID- 11820114
TI  - Technology's. Power & magic.

PMID- 11820115
TI  - Setting the 2003 agenda.

PMID- 11820116
TI  - A helping hand. TMA Physician Services aids physicians in setting up practices.

PMID- 11820117
TI  - Increasing physician impact on the prevention of domestic violence.
AB  - Physicians in their professional organizations have recognized the tremendous
      toll of domestic violence on the safety and health of their patients. Effective
      integration of screening and referral into routine practice has encountered many
      significant barriers, primarily the syndrome of compassion fatigue. This article
      describes how physicians can enhance the safety of families. Universal education
      offers more opportunities for physicians to communicate with survivors and
      perpetrators of violence. Specific documentation by physicians will enhance
      patient care and public health surveillance efforts. Safety planning skills offer
      immediate benefits to patients facing acute dangers. The participation of
      physicians (individually and collectively) on adult intentional fatality review
      boards will make available more specific data and tools for the prevention of
      domestic violence.

PMID- 11820118
TI  - Go back to its roots.

PMID- 11820119
TI  - AMA lacks credibility.

PMID- 11820120
TI  - Collaborative study for the validation of serological methods for potency testing
      of tetanus toxoid vaccines for human use.

PMID- 11820121
TI  - Facing the future ... career choices.

PMID- 11820122
TI  - Preparing for the new millennium.

PMID- 11820123
TI  - In memorium. Dr. Roy Greep, former Dean of the Harvard School of Dental Medicine.

PMID- 11820124
TI  - The role of dentistry in mental health.

PMID- 11820125
TI  - Alumni Day '98 Symposium. The "M" in D.M.D.: new horizons in oral medicine in the
      21st century.

PMID- 11820126
TI  - Floss or die: the link between oral health and cardiac disease.

PMID- 11820128
TI  - Clinical implications of tissue engineering.

PMID- 11820127
TI  - The genetic map of craniofacial anomalies.

PMID- 11820129
TI  - Looking back on six decades of dentistry.

PMID- 11820130
TI  - Research dream team targets oral cancer.

PMID- 11820131
TI  - [Caries-- changing patterns].
AB  - This article briefly describes the pathogenesis of dental caries. It focuses on
      the relevant chemical processes and histological changes in dental enamel. Recent
      studies have shown that the mineral balance at the tooth-oral fluid interface are
      determinants for the occurrence of caries, and more important than the intrinsic
      tissue properties. During periods of low pH, following bacterial metabolism of
      fermentable carbohydrates, enamel is demineralized. However, loss of tissue may
      be compensated by mineral deposition from saliva during subsequent periods at
      neutral pH ('remineralization'). The mineral balance is positively affected by
      the presence of low fluoride levels in the oral fluids. Clinically this becomes
      manifest in the decreasing rates of caries initiation and progression. Also it
      may affect the appearance of incipient enamel lesions, which in turn could
      complicate caries diagnosis. The changing patterns of dental changes thus have
      implications for procedures in preventive and restorative practise.

PMID- 11820132
TI  - [Epidemiology of dental caries in the Netherlands].
AB  - Both in 6- and 12-year-old Dutch children the prevalence of dental caries has
      declined remarkably between 1970 and 1985. However, in 6-year-olds the decline
      terminated after that period, while it continued in the 12-year-olds. In 1986 a
      national dental survey of the caries prevalence of older age categories was
      executed. As no comparable caries data are available from an earlier period of
      time, no certain conclusion can be drawn about changes in adult caries
      prevalence. A comparison of the national data mentioned to data from a country
      where the caries prevalence in children did not decline (former DDR), suggests
      that Dutch adults younger than 25 year have a relatively low caries experience at
      this moment.

PMID- 11820133
TI  - [Individual risk assessment of caries].
AB  - The estimation of individual caries risk factors and the related preventive
      treatment in the dental practice are discussed. Salivary counts of mutans
      streptococci and lactobacilli reflect the bacteriological attack (mutans
      streptococci) and sugar intake (lactobacilli). Caries resistance can be estimated
      by measurement of the salivary secretion rate and buffer capacity. Treatment of
      high caries risk patients should be directed against etiological factors.
      Salivary flow rates and buffer capacity can be stimulated by daily (sugar-free)
      gum-chewing. For the use of fluoridated toothpaste and sugar intake the dentist
      is dependent upon the cooperation of the patient. The bacteriological factor in
      the caries process can be suppressed by application of chlorhexidine varnish.

PMID- 11820134
TI  - [Occult dentine lesions under a clinically intact enamel surface. A
      bacteriological investigation].
AB  - Dentine samples of teeth from patients with occlusal lesions beneath an
      apparently intact enamel surface were bacteriologically examined. For this
      purpose two dentine samples, one from the dentinoenamel junction (A) and one just
      before all caries appeared to be removed clinically (B), were taken under aseptic
      conditions. In most cases the A and B samples contained considerable numbers of
      mutans streptococci and lactobacilli, while the dentine after opening was soft
      with a light colour. These results suggest that one is dealing with active caries
      lesions, which should be treated as such. Comparison of the saliva data from the
      patients group with the saliva data of a control group showed no significant
      differences concerning the numbers of mutans streptococci, secretion rate and
      buffer capacity.

PMID- 11820135
TI  - [Etiology and prevention of root caries ].
AB  - The prevalence of root caries is increasing. An optimal prevention is important
      because of the difficulties encountered in restoring these lesions. The
      pathogenesis of root and enamel caries have strong similarities. Consequently,
      for both the same preventive means should be applied. It is important to adjust
      the intensity of the preventive measures to the risk level of the individual
      patient. For high risk patients the use of chlorhexidine is advised.

PMID- 11820136
TI  - [Caries and fluoride].
AB  - The cariostatic effect of fluoride is well documented, but the exact mechanisms
      of action are still subject of many studies. Re-evaluations of the clinical data
      of water fluoridation studies have confirmed that fluoride can have a pre
      eruptive effect. But in general, the post-eruptive effects of low concentrations
      of fluoride on the de- and remineralisation processes are regarded to be of
      greater importance. Infrequent applications of concentrated fluoride solutions
      may only be effective in demineralised enamel. The Dutch national recommendations
      for the use of fluorides correspond well with the present views on the mechanisms
      of action of fluoride.

PMID- 11820137
TI  - [Xerostomia-related dental caries].
AB  - The initiation and prevention of xerostomia-related dental caries were studied
      using an in situ model. The morphology of induced carious lesions was compared
      with that of natural xerostomia-related dental caries. Both natural and induced
      xerostomia-related dental caries showed the same patterns of decay. Using the in
      situ model three preventive procedures were tested: neutral F gel applied every
      second day or weekly, and a daily rinse with a fluoride mouthwash for a period of
      six weeks. Application of fluoride gel or the use of the fluoride mouthrinse
      resulted in significant inhibition of the demineralization process. Of the
      procedures evaluated fluoride gel applied every second day was the most effective
      in preventing the onset of xerostomia-related dental caries.

PMID- 11820138
TI  - Blood from embryonic cells manufactured.

PMID- 11820139
TI  - Will robots be our future surgeons?

PMID- 11820140
TI  - Endovascular repair of abdominal aortic aneurysm--future reality or doomed to
      failure?

PMID- 11820141
TI  - Hyperbaric oxygen and surgery.
AB  - Hyperbaric oxygen (HBO) therapy, that is the administration of 100% oxygen
      delivered under pressure, has a beneficial effect in several surgical conditions.
      Its use has been assessed and audited and its pharmacological effects
      demonstrated. It is appropriate for use in several surgical conditions as
      evidence-based therapy. These are: (i) gas gangrene; (ii) crush injuries,
      compartment syndromes and acute traumatic ischemias; (iii) enhancement of healing
      in selected problem wounds; (iv) exceptional blood loss anaemia; (v) necrotising
      soft-tissue infections; (vi) refractory osteomyelitis; (vii) radionecrosis;
      (viii) compromised skin grafts and flaps; (ix) thermal burns; (x) intracranial
      abscess. HBO therapy has been used inappropriately in the past; there is also
      lack of knowledge regarding its application, and scarce hyperbaric facilities.
      Hyperbaric therapy, when properly supervised by a physician trained in its use,
      working closely with a surgeon, and ethically used for appropriate indications,
      can be a useful adjunct to surgical practice.

PMID- 11820142
TI  - Improving neonatal transport in the Third World--technology or teaching?
AB  - Neonatal transport in the Third World remains hazardous because of a shortage of
      human and material resources. An audit of the transportation of 126 surgically
      ill neonates was undertaken to identify areas where improvement is possible.
      Failure to maintain simple interventions such as intravenous fluid replacement
      and nasogastric drainage were found to be more important than inadequate
      technology in defining the status of the patient on arrival. Investment in
      education is likely to pay greater dividends than further technological advances.

PMID- 11820143
TI  - Damage control surgery.

PMID- 11820144
TI  - Vesicosuspension for female stress incontinence and cystocele using pubic bone
      anchors.
AB  - OBJECTIVE: The purpose of this study was to evaluate the results of
      vesicosuspension for female stress incontinence and cystocele using fixation with
      pubic bone anchors in a cohort of patients operated on by a single surgeon.
      METHODS: Using a standard questionnaire, an independent female interviewer not
      employed by the surgeon's practice contacted 100 consecutive patients with stress
      incontinence and/or cystocele who had undergone vesicosuspension using suprapubic
      fixation with bone anchors between October 1996 and July 1997. The patients'
      responses were recorded on a computerised database and analysed. All procedures
      were performed by a single surgeon (A.J.V.). The duration of the operation was
      normally 45 minutes, the patient was mobilised on day 3 postoperatively, and the
      catheter removed on day 7. RESULTS: The mean age of the 100 women was 50.4 years
      (range 26-84 years) and the mean follow-up was 11 months (range 1.4-19 months).
      Previous operations for incontinence had been performed in 44 patients.
      Preoperatively 56 patients had to wear protective pads, using an average of 4.4
      pads per day, and 36 had to change underwear because of urine leakage.
      Postoperatively 14 patients had to wear protective pads, using an average of 3.5
      pads per day, while 11 had to change their underwear because of urine leakage.
      Only 3 patients used a catheter to empty the bladder, 2 used medication for
      incontinence, and none had had a subsequent operation for urine leakage.
      Postoperatively 16 patients reported having problems with pain in the pelvis, and
      6 had pain during intercourse, but there were no cases of osteitis pubis.
      Subjective improvement reported by the patients was 93% on average, and overall
      patient satisfaction with the procedure was 8.6 on a scale of 0-10. In total, 89
      patients said they would be prepared to undergo the operation again, while 92
      would recommend it to a friend. CONCLUSION: The use of pubic bone anchors for
      colposuspension is safe and reliable, with results comparable to those of other
      methods, and the added advantages of faster mobilisation and few short-term
      complications.

PMID- 11820145
TI  - Use of intravesical temperature as a monitor of core temperature during and
      following general anaesthesia.
AB  - OBJECTIVE: The value of thermistor-bearing urinary catheters has not been
      extensively investigated in the postoperative period. This study compared
      thermistor-bearing urinary catheters with pulmonary artery catheters as a means
      of measuring core temperature during and following general anaesthesia in
      patients undergoing aortic aneurysmectomy. METHODS: Information was obtained from
      16 patients divided into two equal groups; one group provided intra-operative
      data, and the other group postoperative data. Simultaneous temperature
      measurements were obtained from each of the catheters at specific time intervals-
      every 10 minutes for the duration of anaesthesia and every 30 minutes for 10
      hours during the postoperative period. RESULTS: Agreement between the two
      catheters and the accuracy and precision of the intravesical catheter with regard
      to the pulmonary artery catheter were determined. Clinically acceptable limits of
      agreement between the two methods of measurement were noted, although the limits
      of agreement were somewhat better for the postoperative period. During the early
      intra-operative period the intravesical catheter tended to over-read the
      pulmonary artery catheter, the largest mean difference being +0.3 degree C.
      During the postoperative period the intravesical catheter either under-read or
      over-read the pulmonary artery catheter, depending on whether core temperature
      was rising or falling. Mean differences varied from +0.2 degree C to -0.1 degree
      C. However, neither during the intra-operative nor the postoperative periods were
      statistically significant differences noted between the two measurement methods.
      CONCLUSION: The study indicates that in patients undergoing aortic
      aneurysmectomy, the thermistor-bearing urinary catheter is a clinically
      acceptable measure of core temperature during and following general anaesthesia.

PMID- 11820146
TI  - Salmonella typhi liver abscess.
AB  - We report on the first case of a typhoid liver abscess treated at the Chris Hani
      Baragwanath Hospital in Johannesburg, which responded well to percutaneous
      catheter drainage and intravenous ampicillin therapy.

PMID- 11820147
TI  - [Mortality of breast cancer and frequency of mammography in Hungary].
AB  - The Hungarian breast cancer mortality is above the European average. Because of
      the lack of effective primary prevention, the control has to be based on the
      improving results of treatment which is much more successful in the case of early
      detected cancers. Beyond the patients collaboration and the application of the
      recommended diagnostic protocols, the population based screening programs have
      high importance in achieving earlier diagnosis. This study aimed to describe the
      regional differences of mammography's application as an indicator of diagnostic
      and screening performance. The records of the outpatient services' reports
      containing the code for native X-ray examination of the breast were analysed in
      the period of 01/07/1998 to 30/04/2000. The age specific and the age standardised
      relative frequencies of mammographical examination were determined for the
      Hungarian counties and Budapest. The observed age specific frequency of
      mammography for the whole country was 17, 21, 11 and 4% for the age group of 40
      49, 50-59, 60-69 and 70-74 years, respectively. The lowest observed values were
      10 times smaller than the highest ones in every studied age group. The age
      standardised relative frequency of mammographical examination was higher than the
      national average in Tolna (2.52), Borsod-Abauj-Zemplen (1.48), Zala (1.41),
      Baranya (1.33), and Csongrad (1.27) counties and in Budapest (1.35). The
      described data demonstrates that the Hungarian practice of mammography is far
      from acceptable considering the frequency of application. On the other hand, it
      was also explored that serious geographical differences exist within the country.
      It seems that there are providers that can achieve relative successes in
      diagnosing the breast cancers in as early stage as it is possible. The evaluation
      and utilisation of the experiences of these providers could increase the efficacy
      of interventions organised to improve the Hungarian epidemiological status of
      breast cancer.

PMID- 11820148
TI  - [Changes in lipid profile and paraoxonase activity in obese patients as a result
      of orlistat treatment].
AB  - 257 patients from 33 centres were involved in a six-month study, the aim of which
      was to assess the effect of orlistat together with a diet. The authors examined
      how the treatment effected the anthropometrical and lipid parameters, extending
      the study to the aspect of paraoxonase activity in case of 25 patients. 44
      patients dropped out during the study period due to the lack of sufficient diet
      compliance, whereas 3 patients had to stop the therapy because of the adverse
      event of flatus with discharge. On the average, the body mass of the patients
      decreased from 100.8 +/- 18.9 to 91.3 +/- 18.6 kg, i.e. by 9.5 kgs, while their
      BMI was reduced from 36.1 +/- 5.6 to 32.5 +/- 5.2 kg/m2 and the circumference of
      the waist changing from 119.1 +/- 20 to 108.3 +/- 15.1 cm, i.e. by 10.8 cms. The
      blood sugar level significantly decreased from 5.7 to 5.4, while the cholesterol
      concentration significantly dropped from 5.9 to 5.5, the triglyceride level being
      reduced from 2.4 to 2.1 mmol/l and blood pressure falling significantly from
      136.6/86.9 to 129.9/81.6. All the above changes showed a significant decrease.
      However, the HDL-cholesterol level did not change. The serum paraoxonase activity
      significantly increased (143 +/- 49 vs 166 +/- 43 UL) along with the standardised
      values for HDL (PON/HDL), even compared to the control diet group. From the above
      results it may be concluded that orlistat tends to have an antioxidant effect.

PMID- 11820149
TI  - [Genetic background of rheumatoid arthritis in connection with a family tree].
AB  - Authors present a rare history of a family with accumulation of autoimmune
      diseases. From eight siblings four had rheumatoid arthritis, one systemic lupus
      erythematodes, one primary Sjogren syndrome, and one Reiter disease.
      Interestingly, neither the parents nor the offsprings were affected. Because of
      the possible genetic background, the authors performed HLA serologic and DNA
      investigations in nine members of the family. The results showed, in agreement
      with data from the literature, the accumulation of HLA-DQ7 (DQB1*0301), DR4, B27
      and DR6 (DR13) risk factors. This observation confirms, that the clinical and
      immunogenetic features are different in familiar and sporadic forms of rheumatoid
      arthritis. Authors summarize the genetic background of rheumatoid arthritis in
      connection with this family tree.

PMID- 11820150
TI  - [The role of gastrointestinal ulcer in the differential diagnosis of low back
      pain].
AB  - The authors call on attention for the differential diagnostical problems of low
      back pain and the importance of the Head zones by describing one case. A patient
      was admitted to hospital with severe symptoms of low back pain. In her previous
      medical history there were musculo-skeletal problems for many years in addition
      to continuous medical investigation and treatment for low back pain for three
      months. Careful examination revealed a five-centimetre large gastric ulcer in the
      background of her symptoms.

PMID- 11820151
TI  - [Further data on the subject of endothelial dysfunction].

PMID- 11820152
TI  - [Interview questions on the topic: "Therapy of Hyperlipidemia" directed at Prof.
      Dr. med. Dr. h.c. Dietrich Seidel, Munich (interview by Dr. med. Ulrich Keil)].

PMID- 11820153
TI  - [Drug therapy of hyperlipidemia. Current status in Germany].
AB  - BACKGROUND: Hyperlipidemia is an important, maybe the most important, risk factor
      for coronary artery disease (CAD). Therefore lowering elevated cholesterol is
      crucial for primary and secondary prevention. Dietary treatment but also drug
      therapy is frequently used to lower cholesterol in our days. STATINS: Drug
      therapy with statins has shown to be beneficial in clinical studies. Patients at
      a high risk for CAD will benefit mostly of drug treatment with a statin and in
      one out of 13 high-risk patients statin treatment will prevent one serious
      cardiovascular event [NNT (number needed to treat) = 13]. This is the reason for
      the success story of statins in the last decade. In Germany more than 700 million
      defined daily doses of lipid-lowering drugs are prescribed per year, which is
      sufficient for continuous treatment of 1.9 million patients. However, the broad
      use of statins came along with some thoughtlessness towards side effects. Safety
      laboratory values were not determined, contraindications were not considered to
      be serious enough and the lack of clinical endpoint studies was neglected. In
      addition there was an attempt to disregulate statins as "over the counter drugs"
      in the US--an attempt which was stopped by the intervention of the FDA. This
      practice ended in a series of severe side effects and led to the withdrawal of
      cerivastatin, a new statin from the market. If this will influence the drug
      treatment of hyperlipidemia needs to be seen.

PMID- 11820154
TI  - [Life style changes for prevention of coronary heart disease].
AB  - BACKGROUND: In developed countries arteriosclerosis is responsible for the
      majority of all deaths. With growing prosperity the life expectancy is
      increasing, and cardiovascular disease is becoming the primary cause of premature
      death. Most complications of arteriosclerosis occur unexpectedly. Because of the
      severe morbidity and high mortality prevention is the only true solution. CHANGES
      OF LIFESTYLE: Unhealthy nutrition, physical inactivity, overweight and smoking
      have been identified as the primary causes of arteriosclerotic vascular disease.
      Central obesity is responsible for the risk factors characterizing the metabolic
      syndrome. This is the result of inappropriate caloric intake and expenditure. In
      addition, the nutrients themselves can bear harmful consequences either
      indirectly by deteriorating risk factors like lipid parameters or by affecting
      directly the vessel wall. This can add to the deleterious effects of smoking.
      Evidently saturated fat is the single most decisive nutrient for atherosclerotic
      vascular disease. Cholesterol and trans fatty acids act additive, while
      unsaturated fatty acids appear to be beneficial. However, total fat intake is an
      important determinant of the energy supply, which again influences body weight
      and composite. Physical activity can counteract, but appears to be beneficial by
      several additional ways. Quitting smoking is highly effective already within few
      years. Together with physical activity and healthy nutrition more than 80% of all
      cardiovascular events can be prevented. CONCLUSION: Preventive medicine needs to
      focus on lifestyle changes because they are feasible and highly effective. A
      nutrition low in total fat primarily by avoiding saturated and trans fatty acids,
      but rich in carbohydrates and fiber is recommended. Daily physical activity in
      any preferred way should be encouraged, and quitting smoking needs to be strongly
      emphasized.

PMID- 11820155
TI  - [Hyperlipidemia and fibrates with special reference to diabetes].
AB  - The lipid triad: hypertriglyceridemia, low HDL, small dense LDL represents a high
      risk group for excessive cardiovascular morbidity and mortality in type 2
      diabetes. In poorly controlled diabetes LDL are increasingly oxydized and
      glycosylated whereas HDL degradation is accelerated. The high lipid risk in
      coincidence with the diseases of the metabolic syndrome leads to the conclusion
      that diabetes today is a cardiovascular disease demanding an aggressive
      correction of the lipid triad. The benefit of lipid lowering treatment has been
      proven not only for statins but there is more and more evidence also in favour of
      fibrates. Fibrates are particularly useful in the treatment of
      hypertriglyceridemia/low HDL. This also leads to a reduction in small dense LDL.
      In the case of insufficient correction of LDL a combination with a low dose of a
      statin is recommended. A definite answer with respect to the benefit/risk ratio
      of fibrates should be provided by large ongoing studies with these drugs in
      representative groups of diabetes patients (LDS, TrUMPET, FIELD).

PMID- 11820156
TI  - [Hyperlipoproteinemia and LDL apheresis. Clinical experiences with the H.E.L.P.
      system].
AB  - No question, one of the leading causal factors for early atherosclerosis and
      coronary heart disease (CHD) is the abundance of LDL-cholesterol in the blood,
      exceeding limits of 100 mg/dl. Thus, recommendations for therapy focus on LDL
      levels less than 100 mg/dl. With the introduction of the statins--a very potent
      family of lipid lowering agents--such target levels can be achieved in most of
      the patients, resulting in a drastic decrease of LDL, CHD incidences, as well as
      in a reduction of cardiac and total mortality. There is, however, a remaining
      small group of patients, who is more or less resistant to an adequate combination
      of dietary and drug therapy. For these patients, various techniques of apheresis
      are available for over 15 years. Some of them have been approved by the FDA in
      the US and comparable regulatory offices in Europe. The most extensive
      experimental and clinical experience was gathered with the H.E.L.P.-system of B.
      Braun Melsungen, which differs from other apheresis techniques by its efficiency
      to eliminate LDL, Lp(a), Fibrinogen and CRP simultaneously. The clinical results
      obtained up to day with the apheresis clearly demonstrate a significant reduction
      of risk factors and clinical events, as well as an excellent long-term tolerance.

PMID- 11820157
TI  - [Progression of coronary arteriosclerosis as monitoring the therapeutic success
      of hyperlipidemia].
AB  - BACKGROUND: Coronary calcium represents an integral part of coronary
      atherosclerosis. It results from an actively regulated process and already
      appears in early stages of the disease. Studies using electron-beam computed
      tomography (EBCT) have demonstrated that an accelerated progression of coronary
      calcified atherosclerosis is associated with an increased rate of clinical
      events. In experimental animal models, effective lowering of LDL cholesterol
      stops the progression of coronary calcified atherosclerosis. LDL CHOLESTEROL AND
      PROGRESSION OF CORONARY CALCIUM: A number of EBCT-derived retrospective analyses
      have consistently reported that LDL cholesterol values are the most important
      factor influencing the progression of coronary calcified atherosclerosis. In high
      risk patients with no clinical coronary artery disease who were not specifically
      treated, a mean annual progression of coronary calcium of 52% was observed. In
      the presence of statin drug therapy, progression ranged from -7% through 22%,
      depending on the LDL cholesterol levels during therapy. A preliminary prospective
      investigation has confirmed these results and, in particular, suggested that
      reaching low LDL cholesterol levels < 100 mg/dl effectively stops the progression
      of coronary calcified atherosclerosis. LDL cholesterol independent
      ("pleiotropic") effects of statin drugs could not be demonstrated by using EBCT.
      At present, two large prospective, randomized trials are being conducted which
      analyze the effects of intensified versus standard statin drug therapy on the
      progression of coronary calcified atherosclerosis by EBCT. CONCLUSIONS: Serial
      EBCT studies enable analysis of the interaction between therapeutic measures,
      progression of coronary calcified atherosclerosis and clinical course of the
      patients by virtue of direct visualization of the activity of coronary plaque
      disease. This has already been successfully implemented in small patients groups.
      Validation in the individual patient is pending. Prospective, randomized
      therapeutic trials are expected to yield valuable knowledge for clinical
      practice.

PMID- 11820158
TI  - [Cost effectiveness of lipid lowering therapy].
AB  - BACKGROUND: Due to increasing pressure to save money in the health care sector
      economical evaluations become more and more important. The following article
      deals with cost-effectiveness analyses regarding lipid-lowering therapy. Results
      are discussed in the light of methodological issues. COMPARISON OF EFFECTIVENESS:
      The choice of life years gained as effectiveness parameter facilitates the
      comparison of different therapies. Non-pharmacological therapies were able to
      achieve a reduction of risk factors, but a mortality reduction has not been
      proven so far. COST-EFFECTIVENESS OF STATINS: Own analyses from the perspective
      of the social insurance demonstrate that statins are cost-effective in secondary
      prevention of coronary heart disease (CHD). This confirms results from the
      viewpoint of the statutory health insurance under additional consideration of
      interaction between the various sectors of the social insurance in Germany. In
      primary prevention the cost-effectiveness is strongly related to the initial CHD
      risk. For which risk groups the therapy with statins is both effective and
      efficient depends on the underlying assumptions. Overall accepted threshold
      values for cost-effective therapies could be reached at a yearly risk of coronary
      heart disease of about 1.5%. CONCLUSION: The results should be considered by
      decision makers in the evaluation of statin therapy.

PMID- 11820159
TI  - [Cardiac neurosis].

PMID- 11820160
TI  - [Stretched polyethylene (UHMWPE)--a new substance modification for minimizing
      wear in artificial knee joint replacement].
AB  - Polyethylene wear is a major cause of aseptic loosening of knee endoprostheses.
      With the aim of minimizing this mechanical wear, we stretch-modified the
      structure of polyethylene. From plates of UHMWPE, stretched PE samples were
      produced under defined conditions, and subsequently submitted to friction tests
      in a fluid environment (cycles 5 x 10(5), frequency 1.5 Hz, load 500 N, contact
      stress 10 MPa). After load testing, the stretched samples revealed a 70% reduced
      wear rate in comparison with non-stretched samples. Microscopic examination
      (light microscopy, scanning electron microscopy) showed abrasive scratches in all
      test samples, but only in the non-stretched specimens were signs of pitting
      found. Translating these results to unidirectional tractive rolling on the tibial
      plateau in the knee joint suggests that a significant reduction in polyethylene
      wear can be expected. However, further experimental investigations need to be
      carried out to confirm this highly promising possibility.

PMID- 11820161
TI  - [Investigation of explanted hip and acetabulum hip prostheses].
AB  - Retrieved ceramic femoral heads and acetabular cups were investigated. On the
      basis of the case studies, the reasons for revision are discussed. Wear patterns
      and wear rates were found to differ from those observed in hip simulating
      testing. Monolithic ceramic cups showed a high wear rate. Owing to their limited
      range of motion, ceramic "mushroom heads" are associated with impingement that
      leads to a high risk of cup loosening, high wear rates and in vivo fractures. The
      combination of ceramic "mushroom heads" and cups is not recommended. An
      evaluation of complications shows that some can be explained by patient behaviour
      -e.g. Japanese sitting position, horse riding. Designers need to develop new
      concepts offering a larger range of motion, for example, with head diameters of
      32 and 36 mm that reduce the risk of impingement, subluxation and dislocation,
      while increasing the range of motion. The potential of ceramic/ceramic coupling
      has been known since the 70s, and ceramic concepts for total hip replacement are
      currently experiencing a renaissance, although further developments are still
      possible.

PMID- 11820162
TI  - [Biomechanical studies and finite element analysis of a bone-implant interface].
AB  - In the present study, the fixation system of a femoral medullary nail connection
      was investigated. In surgical treatment of fractured femurs, the fracture is
      bridged by a medullary nail that is fixed by interlocking screws in the bone.
      Bone failure around these screws is the most common complication associated with
      the treatment of fractures of osteoporotic bone. The present study analyses the
      stresses present in the region of the implant/bone system. Three-dimensional
      finite element models were generated, a nonlinear structure analysis performed,
      and the stresses at material interfaces investigated. The highest concentration
      of stresses is to be found in the middle of the interlocking screws and the holes
      drilled in the bone. This is in agreement with the results of experimental
      investigations.

PMID- 11820163
TI  - [The first osseointegrated percutaneous prosthesis anchor for above-knee
      amputees].
AB  - A percutaneous osseointegrated anchoring device for above-knee implantation
      designed to enable permanent attachment of an artificial limb is described. In
      addition to a technical description, the two-stage operative procedure, together
      with the rehabilitation process in an 18-year-old man, is also detailed.
      Following amputation and complete healing of the soft tissues, a surface
      structured metal pin capable of supporting large loads, is driven into the
      medullary canal of the thigh bone. A metal sleeve having an identical surface
      structure serves to close off the medullary canal and provide an interface with
      the soft tissues. Screwed to the end of the pin is a conical metal adapter to
      which is attached a silicone cylinder whose right-angled distal end is located
      subcutaneously and ends in a titanium mesh. The first part of the implantation
      procedure is concluded by closing the silicone cylinder with a plastic plug for 6
      weeks to permit osseous integration and the ingrowth of tissue into the mesh. In
      a second step, the plastic plug is removed via a skin incision, and the permanent
      load-bearing metal adapter fitted. In the above-mentioned patient wound healing
      at the metal/tissue interface was complication-free, since the implanted silicone
      cylinder prevented the "wedge effect" caused by the build-up of "luxuriant"
      tissue. After a further healing phase of 6 weeks, rehabilitation with an
      exoprosthesis took only 2 weeks, after which time, the patient was able to walk
      without a walking aid, and returned to work.

PMID- 11820164
TI  - [A new ISO/FDIS 14242-1 compatible hip prosthesis simulator: E-SIM].
AB  - The continuing development of new, highly sophisticated materials for the
      articulating surfaces of total hip endoprostheses involves the need for testing,
      not only of biocompatibility and dynamic loadability, but also of tribological
      properties (friction, wear, lubrication). For decades, the wear resistance of
      these materials has been tested in wear simulators. In consequence of the
      currently often widely differing test methods, the technical committee (TC 150)
      of the ISO (International Organization for Standardization) has been concerned to
      develop an International Standard (ISO/FDIS 14242 1 and 2: Implants for Surgery-
      wear of total hip joint prostheses--on the basis of kinetic and kinematic data
      from gait analysis. This new standard will be the basis for ensuring the
      comparability of scientific data obtained from tribological testing of total hip
      endoprothesis. The new hip simulator, E-SIM, presented in this paper, complies
      with the currently published FDIS (Final Draft International Standard), and
      enables testing in accordance with these specifications.

PMID- 11820165
TI  - [The distal radius and surrounding soft tissues--ultrasound anatomy and
      ultrasound pathology in the adult and child].
AB  - BACKGROUND: The aim of the study was to evaluate the ultrasonographic anatomy of
      the distal forearm (i.e. distal radius and surrounding soft tissue) and the
      typical changes occurring during growth, in adults and children. MATERIAL AND
      METHODS: The ultrasonographic anatomy was evaluated in 10 healthy adults aged
      between 20 and 60 years, and 20 healthy children aged between 2 and 18 years.
      Particular attention was paid to dynamic examination comparing both limbs, and
      isolated investigations of functional tendon. RESULTS: An anatomical description
      of the tissues of the distal forearm was possible at all ages. During growth,
      secondary ossification centres and the transitional osteochondral region of the
      growth plate need particular consideration. DISCUSSION AND CONCLUSION: Both in
      children and adults, ultrasonography can provide valuable information in the
      evaluation of acute trauma, follow-up of fractures and osteosynthesis, suspected
      osteomyelitis and chronic disorders. In children, special attention must be paid
      to the development of the epiphyseal region, as reflected by ossification centre,
      growth plate and articular cartilage.

PMID- 11820166
TI  - [Therapeutic strategies in type 2 diabetes].
AB  - UKPDS and DCCT studies have demonstrated the critical role of tight glycaemic
      control to reduce the micro- and macro-vascular damage linked to diabetes.
      Unfortunately, the insulin requirement of type 2 diabetic patients remains
      elevated since 5 to 7% of these patients will required, yearly, a change from
      oral antidiabetic drug to insulin treatment to maintain a good glycaemic control.
      This manuscript is intended to review the currently available oral antidiabetic
      drugs, their benefits as well as potential arms and to propose a simplified
      therapeutic strategy in presence of type 2 diabetes.

PMID- 11820167
TI  - ["MODY" diabetes. Beyond a monogenic disease].
AB  - Maturity Onset Diabetes of the Young is a particular form of type 2 diabetes,
      classically defined by an autosomal dominant inheritance, a young age at
      diagnosis (before 25 years) and an insulin secretion defect. At this time, six
      MODY genes have been described. Beyond the apparent simplicity, the study of such
      monogenic model of disease may help us to approach a complex disease such as type
      2 diabetes, where is involved to conserve a genetic and environmental factors
      network. This different approach may help us to better understand type 2 diabetes
      physiopathology.

PMID- 11820168
TI  - [Diabetic foot: a public health problem too often underestimated. Consequences
      and therapeutic possibilities].
AB  - The clinical screening of diabetic patients at risk for foot ulcer should be
      regularly performed by all physicians and health professionals in charge of these
      patients. In addition, the high risk patient should be also educated to detect
      high risk foot lesions. This step represents the first strategy in order to
      prevent this too frequent complication of diabetes mellitus. The amputation which
      represents the most dramatic evolution of foot ulcer, has profound psychosocial,
      economic and functional effects on diabetic patients. For these reasons a global
      strategy should be developed in order to reduce the incidence of diabetic foot
      ulcer. A systematic follow-up strategy in high risk patients is highly
      recommended. The patient education is one of the most important step for the
      success of this strategy.

PMID- 11820169
TI  - [Diabetic nephropathies: therapeutic aspects].
AB  - The incidence of diabetic nephropathy has declined these last decades, but
      diabetes mellitus still remains the commonest cause of end-stage renal failure,
      due to an increased prevalence of diabetes mellitus and a longer life expectancy
      for diabetic patients. The aim of this review is to describe the natural history
      of diabetic nephropathy and discuss the influence of many factors such as genetic
      and non-genetic progression promoters, hypertension, hyperglycemia, dyslipidemia,
      proteinuria and tobacco. Because only a comprehensive treatment strategy of these
      promoters will reduce the risk of end-stage renal failure, the inclusion of
      cardiovascular risk factors management and the screening of cardiovascular
      disease will further contribute to reduce the very high mortality of diabetic
      patients suffering of diabetic nephropathy.

PMID- 11820170
TI  - [Farewell address: a tour of my office].

PMID- 11820171
TI  - [Cardiovascular diseases in diabetes].

PMID- 11820172
TI  - [20-year-old patient with pseudogout].

PMID- 11820173
TI  - [New infectious diseases].

PMID- 11820174
TI  - [Helicobacter pylori and cytomegalovirus infection and atherosclerosis: an
      assessment of the current status].
AB  - An association between Helicobacter pylori infection or cytomegalovirus infection
      and atherosclerosis has been described. During the last four years, new evidence
      evolved from a number of studies, which allows to reevaluate the clinical impact
      of this association. Current knowledge suggests that the association between
      atherosclerosis and Helicobacter pylori may be accounted for by chance or by
      confounding from a secondary phenomenon. Regarding cytomegalovirus, a number of
      animal models and molecular studies propose several different mechanisms, by
      which the virus may interact with cells of the vessel wall, the immune system or
      with some of the established risk factors to cause atherosclerosis. Conclusive
      evidence for the clinical relevance of these experimental findings is still
      lacking. Some of the uncertainties may be resolved by larger studies, which have
      started during the last years.

PMID- 11820175
TI  - [Chlamydia pneumoniae--chronic infection and atherosclerosis].
AB  - Recent evidence suggests that common chronic infections may contribute to the
      initiation and/or progression of atherosclerosis. Infection of the vascular wall
      with Chlamydia pneumoniae, a gramnegative bacterium, has been linked with
      coronary heart disease, myocardial infarction and stroke in epidemiological
      studies and in pathological studies using immunohistochemistry and electron
      microscopy. In addition striking evidence for an active role of Chlamydia
      pneumoniae in atherogenesis has been provided in animal models and from
      preliminary data of intervention trials. Although these observations strongly
      indicate an involvement of Chlamydia pneumoniae in the pathogenesis of
      atherosclerosis, a causal relationship has not been established yet. In the last
      years several interesting papers have dealt with the molecular mechanisms how an
      infection with Chlamydia pneumoniae affects the vascular wall to initiate or
      facilitate vascular dysfunction.

PMID- 11820176
TI  - [Infection hypothesis of coronary heart disease].
AB  - It is well accepted that coronary artery disease is linked to an inflammatory
      process. It is unproven however whether either infectious agents may cause or
      accelerate coronary artery disease or the inflammatory process is due to
      metabolic or toxic effects. Among the possible infectious agents Chlamydia
      pneumoniae is the most likely bacterium involved in atherosclerosis. The
      arguments in favour of Chlamydia pneumoniae originate from seroepidemiologic
      studies and from detection and isolation of bacteria from vascular lesions. This
      review summarises the present understanding of the role of bacterial infection
      for development or progression of coronary artery disease.

PMID- 11820177
TI  - [Prevention and therapy of infections in tumor patients].
AB  - The neutropenic patient with fever remains a great challenge. Because of the high
      risk of life-threatening bacterial infections, all febrile neutropenic patients
      should be treated with broad-spectrum bactericidal antibiotics promptly by the
      intravenous route and in maximal therapeutic dosages. Although the currently
      available diagnostic tests are not sufficiently rapid, sensitive, or specific for
      identifying or excluding the microbial cause of a febrile episode, a careful
      diagnostic work-up should be done. The concern about the problem of emerging drug
      resistance bacteria due to extensive antibiotic use, plus the fact that such
      prophylaxis has not been shown to reduce mortality rates, led to the
      recommendation that routine prophylaxis with these antibiotics in neutropenic
      patients be avoided. Vaccination should be emphasized in these patients.

PMID- 11820178
TI  - [To see from light--biophysics of visual signal transduction].
AB  - To perform their functions within an organism, or to adapt to the environment as
      single cells, living cells react to signals detected by highly specialized
      receptor proteins. These include the G-protein coupled receptors (GPCRs), a
      receptor family, which comprises more than 1000 members, and is of outstanding
      significance in basic research and medical application. An archetype of a GPCR is
      the visual pigment rhodopsin, the photoreceptor of the retinal rod cell.
      Biophysical methods have largely contributed to the elucidation of rhodopsin
      structure and function, as well as of the corresponding signal cascade. This
      article discusses some of the more recent developments.

PMID- 11820179
TI  - [understanding and radiation hygiene assessment of solar UV exposure in Germany].
AB  - In order to monitor the natural ultraviolet (UV) radiation and to assess it from
      the point of view of radiation hygiene, the Federal Office for Radiation
      Protection (BfS) and the Federal Environmental Agency (UBA) have built up a
      common network for UV monitoring. Since 1993, the ground-level solar UV radiation
      has been measured at four sites in Germany every 6 minutes, with
      spectroradiometers in the wavelength range between 290 and 400 nm. Because
      erythema (sunborn) is of special interest in terms of radiation hygiene, the
      erythemal weighted irradiance was used as a measure for the biological effect of
      UV exposure. For this purpose, the measured spectral irradiance was multiplied by
      the relative erythemal weighting function, and the resulting function integrated
      from 290 to 400 nm. In the summer months of June and July 1999, the erythemal
      irradiance exceeded regularly the value of 175 mW/m2 in the south of Germany. In
      the north, values of not less than 160 mW/m2 were measured during this period.
      These values correspond to an UV index of more than 7 or 6, respectively--a high
      exposure regarding to the classification of the German Radiation Protection
      Commission (SSK), for which (absolute) sun protection is recommend. Between 1995
      and 1999, the four sites were characterized by a small increase of the ground
      level UV exposure of approx. 10%. Nevertheless, in consideration of the manifold
      factors affecting the acquired data, the measuring period of 5 years is still
      insufficient to demonstrate an ozone-dependent effect.

PMID- 11820180
TI  - [Illustration of elasticity differences using MR-elastography].
AB  - Differences of elasticity in tissue phantoms with inclusions of different
      elasticity were mapped by means of MR elastography (MRE). This new magnetic
      resonance imaging technique is based on the phase shift of the MR signal by
      switching a motion sensitizing magnetic field gradient simultaneously with the
      coupling of a shear wave. Wave patterns showing snapshots of the shear wave that
      propagates through the investigated substance were depicted in tomographic phase
      images. It was investigated wether a visualization of differences in elasticity
      of soft tissues was possible on the basis of differences in the wavelength. For
      this purpose, tissue phantoms with cylindrical inclusions were produced from agar
      gels, with agar concentrations between 1.0 and 1.5%. The diameters of the
      inclusions were of the order of a few centimetres. For diameters as small as 4
      cm, there were still distinct differences in the wavelength between the matrix
      and the inclusion. The results of our study suggest that this technique has the
      potential for future application as an additional imaging method for tumor
      detection.

PMID- 11820181
TI  - [Analysis of the convergence relation of reconstructed algorithms disregarding
      local and global visual evaluations].
AB  - Tomographic reconstruction methods used in positron emission tomography are
      classified in two major groups: the traditionally and still widely applied
      filtered backprojection, and the iterative methods based on statistical models.
      This study focused on the objective comparison of different reconstruction
      algorithms, excluding criteria based on pure visual evaluation. The evaluation
      criteria were mathematically defined parameters, i.e., mean square error,
      standard deviation, signal-to-noise ratio and contrast recovery. The methods used
      for comparison were the classical filtered backprojection, the maximum likelihood
      expectation maximization algorithm, the maximum a-posteriori reconstruction model
      based on the Bayes Theorem, as well as the acceleration algorithms based on
      ordered subsets and high over-relaxation. These algorithms were evaluated by
      means of a mathematical brain phantom and of a physical spherical phantom. In
      terms of the applied parameters, the majority of the experiments showed a
      quantifiable superiority of the iterative methods compared the filtered
      backprojection.

PMID- 11820182
TI  - CT based lung density correction verification with in vivo dosimetry using
      diodes.
AB  - In vivo dose measurements with diodes are easy to perform. The first aim of our
      study was to show whether diode measurements of the patient exit doses are
      precise enough for verifying inhomogeneity corrections used for treatment
      planning. The second aim was to assess the precision of the modified Batho Law
      inhomogeneity correction of the CadPlan treatment planning system. For this
      purpose, entrance and lait doses were measured in the thoracic region of 115
      patients. Diode measurements were sufficiently precise to verify the density
      corrections predicted by the treatment planning system (< 0.5% of ICRU dose). The
      measured doses were compared with calculations of the CadPlan treatment planning
      system. The mean deviation of the exit dose calculations within the measurements
      error was zero. The present results show that measurements of exit dose even in a
      small number of patients are sufficient to identify systematic errors in the dose
      calculation.

PMID- 11820183
TI  - [A simple dose-effect model for the optimization of IMRT].
AB  - Optimization of percutaneous photon beams with intensity modulation was
      investigated in terms of the influence of different dose-effect functions for
      lung tissue on the resulting dose distributions. The fluence profiles were
      optimized for a cylindrical phantom with a L-shaped target, the spinal cord and
      lung presenting the critical organs. Concurrent criteria were a minimum dose
      constraint for the target and a maximum dose constraint for the spinal cord. The
      dose effect in the lung was minimized using different approaches. All tested
      approaches were able to control the dose distribution in the lung. The mean dose
      remained constant, where as the volume of low dose could be changed. Due to the
      simplicity of functions and parameters, these models are suitable for clinical
      implementation.

PMID- 11820184
TI  - [Standardization of a reference dosimeter system for radiotherapy in
      Switzerland].
AB  - The Swiss ordinance on radioprotection prescribes the periodic verification of
      the reference dosimeter systems for radiotherapy. The corresponding modalities
      were elaborated by an interdisciplinary collaboration of representatives of all
      concerned institutions. The modalities require in particular that the
      verifications are performed with the radiation qualities used in the hospitals.
      The verification concept is already realized for high energy photon radiation and
      for low and medium energy X-rays. The measurement capabilities for the
      verification with high energy electron beams are in preparation. The tasks to
      verify the reference dosimeter systems are divided between the Swiss Office of
      Metrology and Accreditation, METAS, and the Institut Universitaire de
      Radiophysique Appliquee, IRA. The corresponding metrological infrastructure and
      measurement capabilities of both institutes are presented. In particular, the
      traceability of the standards used for the verification to national and
      international primary standards and thus to the SI system of units is explained.
      The primary standards established and operated by METAS are briefly described.

PMID- 11820185
TI  - Writing on the wall.

PMID- 11820186
TI  - Reducing the risk of aviator-multifunction display interface problems with human
      factor models and optimization design methods.
AB  - Multifunction display and control systems (MFDCSs) in modern cockpits use
      computer-generated graphics and symbology that have integrated and largely
      replaced the myriad discrete electromechanical flight instruments found in older
      aircraft. While much is known about the physical and visual properties of MFDCSs,
      less is known about which human factors are the most important for optimum design
      and use. Reports in the literature indicate that poor MFDCS design can adversely
      influence flight performance. However, current MFDCS content design methods do
      not quantify the relative importance of different cognitive and psychomotor
      factors. This article discusses the need for practical human factors-oriented
      MFDCS design tools to optimize the distribution of systems information and
      functionality. Such advances may lead to better designed MFDCSs that reduce
      aircrew workload and stress and improve flight performance during both routine
      and emergency procedures.

PMID- 11820188
TI  - Current world literature. Benign prostatic hyperplasia.

PMID- 11820187
TI  - Research in developing countries.

PMID- 11820189
TI  - Current world literature. Urinary tract infections and sexually transmitted
      diseases.

PMID- 11820190
TI  - Model behavior.

PMID- 11820191
TI  - "Faith vs. death: the problem with medicine's faith factor theology".

PMID- 11820192
TI  - "Faith versus death: the problem with medicine's faith factor theology".

PMID- 11820193
TI  - "Should religiosity be included in the medical history"?

PMID- 11820194
TI  - Developing a Web site for your practice, Part 2.

PMID- 11820195
TI  - Financial ratios and group practice operations.

PMID- 11820196
TI  - Apparent activation of cardiovascular A1 adenosine receptors by A3 agonists.

PMID- 11820197
TI  - FDA accuses Red Cross of unsafe practices. Inspections at embattled blood bank
      turn up 'serious' violations.

PMID- 11820198
TI  - Texas immigration care flap subsides.

PMID- 11820199
TI  - The FDA's reaction to corporate compliance audits.

PMID- 11820200
TI  - Corporate compliance programs for FDA-regulated companies: incentives for their
      development and the impact of the federal sentencing guidelines for
      organizations.

PMID- 11820201
TI  - Regulation of cosmetics that are also drugs.

PMID- 11820202
TI  - Second thoughts: do the FDA's responses to a fatal drug trial and the AIDS
      activist community's doubts about early access to drugs hint at a shift in basic
      FDA policy?

PMID- 11820203
TI  - GATT implementation and generic drug approval.

PMID- 11820204
TI  - A sad story told sadly: the prospects for U.S.-EU food trade wars.

PMID- 11820205
TI  - Data trends. Significant increases in maintenance labor rates of concern.

PMID- 11820207
TI  - 2001: a wonderful year of growth for PET.

PMID- 11820206
TI  - Making Public Health Nutrition relevant to evidence-based action.

PMID- 11820208
TI  - Radiopharmaceutical issues.

PMID- 11820209
TI  - Nuclear medicine and chemistry.

PMID- 11820210
TI  - NIBIB: the new member of the National Institutes of Health.

PMID- 11820212
TI  - SNM public affairs: a year of unexpected events, member activism, and hints of
      things to come.

PMID- 11820213
TI  - History corner: the first commercial radioisotope shipment.

PMID- 11820216
TI  - Identification of dendritic cells in aortic atherosclerotic lesions in rats with
      diet-induced hypercholesterolaemia.
AB  - We have previously identified dendritic cells (DCs) in the intima of human large
      arteries. These vascular DCs are common in atherosclerotic lesions but their
      immature forms are also present in normal arterial intima. Pathophysiological
      studies on vascular DCs are limited because they have only been studied in human
      specimens obtained at operation or post-mortem. The aim of the current study was
      to determine whether DCs participate in the development of atherosclerotic
      lesions in hypercholesterolemic rats. Male Wistar rats were divided into a
      control (n=13) and experimental cohort (n=48). The experimental animals were fed
      an atherogenic diet and 1% saline, while the controls were fed standard rat cubes
      and water. The aortas were obtained from both groups at 10, 20, and 30 weeks
      following commencement of the diet. An en face immunohistochemical technique,
      routine section immunohistochemistry, and transmission electron microscopy were
      used to detect the presence of DCs in the aortas. Examination of the aortas
      showed that S100+ cells with dendritic cell morphology were present in the aortic
      intima of hypercholesterolemic rats. The S100+ DCs displayed immunopositivity for
      OX-62 and MHC Class II antibodies. Within various types of atherosclerotic
      lesions, these cells were clustered throughout the intima but were especially
      prominent around arterial branch-points where they co-localized with various cell
      types, including T-cells and macrophages. Ultrastructural analysis confirmed the
      presence of cells with characteristics typical of DCs. These features included
      the presence of a well-developed tubulovesicular system, dendritic processes, and
      a lack of secondary lysosomes and phagosomes. This study establishes the presence
      of DCs in the aortic intima of rats with diet-induced atherosclerosis. The
      presence of DCs in this model of experimental atherogenesis could provide a new
      approach to investigating the function of DCs and may help clarify the immune
      inflammatory mechanisms underlying atherosclerosis.

PMID- 11820217
TI  - Dietary mistletoe lectin supplementation and reduced growth of a murine non
      Hodgkin lymphoma.
AB  - The growth of a murine non-Hodgkin lymphoma (NHL) tumour has been shown to be
      reduced by incorporating mistletoe lectin (ML-1) into the diet. The morphological
      characteristics of NHL tumours in mice fed ML-1-supplemented diets were different
      from those in LA (control)-fed mice. The degree of mitotic activity was lower and
      nuclear area reduced. The degree of lymphocyte infiltration was increased in
      tumours from ML-1 fed mice and this was accompanied by a high incidence of
      apoptotic bodies. Visual observation of NHL tumours from individuals fed ML-1
      diet showed a poorly developed blood supply in contrast to control-fed mice. A
      major reduction in number of blood capillaries in NHL tumours was confirmed by
      microscopic evaluation of tumour sections. The results suggested an anti
      angiogenic response in ML-1-fed mice. The feeding of ML-1 compared to control
      diet thus provided several identifiable changes in the morphology of NHL tumours
      which were consistent with the observed reduction in tumour weight. There was no
      longer histological evidence of viable tumour in 25% mice fed the ML-1 diet for
      11 days. Morphological studies of the small bowel indicated (a) that the lectin
      induces hyperplasia, and (b) that the lectin binds avidly to lymphoid tissue of
      Peyer's patches. There was evidence of limited endocytosis of the lectin. An
      experiment where ML-3 was added to the diet of mice three days after inoculation
      of tumour cells showed that the lectin was able to slow down further growth of an
      established tumour. The results show that ML lectins induce powerful anti-cancer
      effects when provided by the oral route.

PMID- 11820218
TI  - The glycoconjugate sugar residues of the sessile and motile cells in the thymus
      of normal and cyclosporin-A-treated rats: lectin histochemistry.
AB  - It is well known that cell surface glycoconjugates play a determinant role in
      cellular recognition, cell-to-cell adhesion and serve as receptor molecules. T
      lymphocytes are in strict contact with the thymic epithelial cells, which control
      their process of maturation and proliferation. On the other hand the normal
      maturation of the epithelial cells is believed to be induced by T-lymphocytes.
      For these reasons we have studied the glycoconjugates saccharidic moieties of the
      sessile and motile cells in the thymus of normal male albino Wistar rats and
      their changes following cyclosporin-A treatment, using a battery of seven HRP
      lectins. Cytochemical controls were performed for specificity of lectin-sugar
      reaction. Some sections were pre-treated with neuraminidase prior to staining
      with HRP-lectins. Our results have demonstrated, in the control rats, a large
      amount and a variety of terminal and subterminal oligosaccharides within and/or
      on the epithelial thymic cells and in macrophages. After cyclosporin-A treatment,
      among the thymic epithelial cells, the subcapsular, paraseptal and perivascular
      cells showed the loss of some sugar residues, which characterized the same cells
      in the intact thymus. Some hypotheses are reported on the role played by the
      glycoconjugate sugar residues in control and cyclosporin-A treated rats.

PMID- 11820219
TI  - Serial plasma concentrations of atrial natriuretic peptide, plasma renin
      activity, aldosterone, and antidiuretic hormone in neonates on extracorporeal
      membrane oxygenation.
AB  - To obtain information on water and salt regulating hormones and volume
      homeostasis during neonatal extracorporeal membrane oxygenation (ECMO), serial
      determinations of atrial natriuretic peptide (ANP), plasma renin activity (PRA),
      aldosterone (Aldo), antidiuretic hormone (ADH), colloid-osmotic pressure (COP),
      osmolality (Osmol), and central venous pressure (CVP) before, during, and after
      neonatal ECMO in 10 neonates with meconium aspiration syndrome (MAS) were carried
      out. Mean gestational ages and birth weights were 41(+3) weeks (39(+6) - 42(+4))
      and 4,063 gm (3,500-4700), respectively; mean age at start and duration of ECMO
      29.3 (14-69) and 152.6 hr (92-267), respectively. Plasma ANP (mean +/- SD) was
      67.8+/-69.1 pmol/L before, decreased to 33.3+/-22.1 (not significant) pmol/L
      during, and significantly increased to 274.6+/-131.8 pmol/L after ECMO (p <
      0.05). ANP correlated positively with CVP (r = 0.63; p < 0.001). Pre-ECMO PRA,
      Aldo, and ADH were comparable to those described earlier in normal neonates,
      decreased during (p < 0.001 for Aldo; p < 0.05 for PRA and ADH) and either
      remained elevated (PRA, p < 0.001; Aldo, p < 0.05) or decreased (ADH) after ECMO.
      COP and Osmol remained unchanged. Neonatal ECMO for MAS is characterized by
      circulatory and osmotic equilibrium. It is suggested that circulating volume
      contracts during and expands after neonatal ECMO for MAS.

PMID- 11820220
TI  - Effects of heat/citric acid reprocessing on high-flux polysulfone dialyzers.
AB  - The surface features, morphology, and tensile properties of fibers obtained from
      pristine, reprocessed, and reused Fresenius Polysulfone High-Flux (Hemoflow F80A)
      hemodialyzers have been studied. Scanning electron microscopy of the dialyzer
      fibers revealed a dense skin layer on the inner surface of the membrane and a
      relatively thick porous layer on the outer surface. Transmission electron
      microscopy and atomic force microscopy showed an alteration in membrane
      morphology due to reprocessing and reuse, or to a deposition of blood-borne
      material on the membrane that is not removed with reprocessing. Fluorescent
      microscopy images also showed that a fluorescent material not removed by
      heat/citric acid reprocessing builds up with continued use of the dialyzers. The
      tensile properties of the dialyzer fibers were not affected by the heat/citric
      acid reprocessing procedure. The protein layers formed on pristine and reused
      hemodialyzer membranes during clinical use were also studied using sodium dodecyl
      sulfate polyacrylamide gel electrophoresis and immunoblotting. A considerable
      amount of protein was found on the blood side of single and multiple use
      dialyzers. Proteins adsorbed on the dialysate side of the membrane were
      predominantly in the molecular weight region below 30 kDa. Little protein was
      detected on the membranes of reprocessed hemodialyzers.

PMID- 11820221
TI  - Generic values for soil-to-plant transfer factors of radiocesium.
AB  - There is a need for soil-to-plant transfer factors of radionuclides that take
      into account all possible crops on all soil varieties to support dose assessment
      studies. Because only limited experimental data exist for worldwide soil systems,
      such values should necessarily have a generic character. This paper describes a
      generic system for 137Cs, mainly based on a reference soil-to-plant transfer
      factor which depends solely on soil properties such as nutrient status,
      exchangeable K-content, pH and moisture content. Crops are divided into crop
      groups, cereals serving as reference group. The transfer of other crop groups can
      be calculated by multiplying data for cereals by a conversion factor. Existing
      data present in the IUR (International Union of Radioecologists) databank and in
      large part the work of a FAO (Food and Agriculture
      Organisation)/IAEA(International Atomic Energy Agency)/IUR project on tropical
      systems provided the basis for the derivation of the conversion factors and
      reference values.

PMID- 11820222
TI  - The duration of lactational amenorrhoea in urban Bangladeshi women.
AB  - The duration of lactational amenorrhoea, and infant feeding patterns and
      behaviour, were investigated in a sample of 97 mother-infant pairs living in a
      poor urban area of Dhaka, Bangladesh. A seven-hour time allocation method was
      used to determine the number of breast-feeding bouts and their duration. The
      seven-hour observation period was conducted on five occasions: at birth, 1 month,
      4 months, 8 months and either 10 or 11 months. The median duration of lactational
      amenorrhoea was determined to be 24.07 weeks using survival analysis. Mothers who
      breast-fed their babies for longer and more frequently had, on average, a longer
      period of lactational amenorrhoea. There was no relationship between
      sociodemographic characteristics of the mother and duration of lactational
      amenorrhoea, nor was there any significant relationship between maternal
      anthropometry and birth weight of the baby and duration of lactational
      amenorrhoea, but there was a tendency for women with lower body mass index to
      have longer durations. Using the Cox proportional hazards model, the best
      predictor of duration of lactational amenorrhoea was the mean of months 0 and 1
      durations of breast-feeding, adjusted for the mean frequencies for those months.
      The introduction of weaning food was also an important predictor.

PMID- 11820223
TI  - Effective dose in paediatric computed tomography.
AB  - There is limited data currently available for making dose and risk assessments
      for paediatric patients undergoing computed tomographic examination. A method has
      been developed to correlate the risk-related quantity, effective dose, to the
      more simply derived quantity dose-length product. This involved scanning a series
      of paediatric anthropomorphic phantoms containing thermoluminescent dosimeters to
      measure effective dose for scans of various anatomic regions. The quantity
      effective dose per dose-length product was calculated and plotted as a function
      of patient size. This showed a simple exponential relationship, and equations of
      fit were derived to enable the calculation of effective dose for a patient of any
      size. Measurements carried out on a second scanner and for alternative scan
      volumes indicated that the method could be generally utilized.

PMID- 11820224
TI  - Variations in skin dose associated with linac bed material at 6 MV x-ray energy.
AB  - Treatment with radiotherapy x-rays at 6 MV energy produces a build-up effect
      whereby a smaller dose is delivered to the patient's skin compared to the tumour
      dose. With anterior fields, no material is normally placed over the patient's
      skin, thus providing the maximum skin sparing possible with the beam
      configuration used. A posterior beam normally passes through the treatment couch
      top and increases the dose delivered to the patient's skin. Both the Mylar
      sheeting and the support ribbing material produce a significant increase in skin
      dose. Measurements at 6 MV have shown that the basal cell layer dose can be
      increased by up to 51% of maximum dose with a carbon fibre/Mylar couch and by 28%
      for a tennis string/Mylar couch when compared to anterior beams. These values are
      associated with the position of the carbon fibre or tennis string ribbing. Dermal
      layer doses are increased by up to 30 and 24% of maximum dose for carbon fibre
      and tennis string, respectively. These values include a combination of dose due
      to the support ribbing and the Mylar sheeting. Due to the variability in patient
      positioning on the couch top, these increases would be spread out over the skin
      surface producing an average increase per unit area at the basal layer of up to
      32 and 20% of the maximum, respectively, for carbon fibre and tennis string couch
      tops and 21 and 12% at the dermal layer compared to dose at Dmax.

PMID- 11820225
TI  - 'Nonspecific' rather than 'nonassociative' pathways to phobias: a commentary on
      Poulton and Menzies.
AB  - This commentary attempts to clarify the nature of contemporary associative
      accounts of phobias, and to describe how they might contribute to the explanation
      of the diversity of phobic aetiologies. It is argued that conditioning-equivalent
      associations underpin all phobic conditions, and that the role of experimental
      psychopathology research is to determine how these associations are acquired. The
      commentary then proceeds to discuss some of the theoretical problems with the
      nonassociative account of phobias as it is currently described by Poulton and
      Menzies, and to suggest that some interpretations of their retrospective and
      prospective data may not be incompatible with contemporary associative accounts.
      The outcome of this is that it may be more suitable to describe the fourth
      pathway to phobia acquisition described by Poulton and Menzies as a 'nonspecific'
      rather than a 'nonassociative' pathway.

PMID- 11820226
TI  - Endothelial dysfunction in patients with coronary artery disease: a comparison of
      three frequently reported tests.
AB  - BACKGROUND: Endothelial dysfunction is useful in predicting future cardiovascular
      disease. At present several tests are available to test endothelial function:
      coronary diameter response to acetylcholine, forearm bloodflow (FBF) response to
      acetylcholine, and brachial artery flow-mediated dilative (FMD) response to
      postischemic hyperemia. This study aimed to compare the three most frequently
      reported endothelial function tests. METHODS: Twenty-eight patients (19 males and
      nine females, mean age 57 years) referred for diagnostic coronary angiography
      were considered for endothelial function measurement in the coronary artery as
      well as in the forearm by FBF and FMD. RESULTS: Acetylcholine decreased the mean
      coronary diameter by 7.4% (SD 6.3%) and increased the mean FBF by 230% (SD 152%).
      Hyperemia increased the mean brachial diameter by 6.7% (SD 4.8%). The effect of
      acetylcholine on forearm resistance vessels was significantly related to the
      effect of acetylcholine on the coronary conduit vessels (P=0.039). Nonetheless,
      FMD was not related to FBF nor to the coronary response. CONCLUSION: In patients
      with mild coronary endothelial dysfunction, forearm vasoreactivity is related to
      the coronary response, provided that the same stimulus is used.

PMID- 11820227
TI  - Cancer nursing practice development: understanding breathlessness.
AB  - This paper considers methodological and philosophical issues that arose during a
      multi-centre, randomized controlled trial of a new nursing intervention to manage
      breathlessness with patients with primary lung cancer. Despite including a
      diverse range of instruments to measure the effects of the intervention, the
      uniqueness of individuals' experiences of breathlessness were often hidden by a
      requirement to frame the study within a reductionist research approach. Evidence
      from the study suggests that breathlessness is only partly defined when
      understood and explored within a bio-medical framework, and that effective
      therapy can only be achieved once the nature and impact of breathlessness have
      been understood from the perspective of the individual experiencing it. We
      conclude that to work therapeutically we need to know how patients interpret
      their illness and its resultant problems and that this demands methodological
      creativity.

PMID- 11820228
TI  - A pluralistic evaluation of nursing/practice development units.
AB  - Nursing/practice development units (N/PDU) are perceived as centres for
      pioneering, evaluating and disseminating innovative practice development and
      facilitating the professional development of practitioners. This paper reports on
      a pluralistic evaluation research study of the nursing/ practice development unit
      accreditation programme provided by the University of Leeds, UK. Individual and
      focus group interviews were undertaken with key stakeholders involved in six
      nursing/practice development units. These included: clinical leaders, team
      members, executive nurses, trust board members, general medical practitioners,
      nursing/practice development unit steering group members, and accreditation panel
      members. Stakeholder perceptions of what constituted a successful
      nursing/practice development unit were elicited and then used to judge the
      success of the programme. Seven criteria for judging the success of
      nursing/practice development units were identified. These were: achieving optimum
      practice; providing a patient-orientated service; disseminating innovative
      practice; team working; enabling practitioners to develop their full potential;
      adopting a strategic approach to change and autonomous functioning. The findings
      highlighted differences between the rhetoric of a successful nursing/practice
      development unit and the reality in which they function. Whereas all the units
      were actively involved in innovative practice development, evaluation,
      dissemination and networking activities, several factors influenced the success
      of the units, in particular, the role of the clinical leader, the motivation and
      commitment of nursing/practice development unit members, financial resources, and
      the nature of support from managers, medical staff and education institutions.
      Although the nursing/practice development units had made significant progress in
      developing both healthcare practice and practitioners, there is still a need to
      consider how the claim that nursing/practice development units benefit patients
      can be substantiated.

PMID- 11820229
TI  - An evaluation of a local clinical supervision scheme for practice nurses.
AB  - This paper presents the findings of an evaluation of a local clinical supervision
      scheme for practice nurses in Leicestershire, UK. A baseline and a follow-up
      postal questionnaire were sent to all practice nurses (including supervisors) and
      general practice senior partners to find out how far the objectives of the local
      scheme had been met during the first year of implementation. Two focus groups
      gathered qualitative data about the process of implementation. Twelve months
      after implementation 12% of practice nurses and over two thirds of GPs reported
      that they were unaware of the scheme. Forty-three percent of practice nurses did
      not know who their local supervisor was; most reported that they would like to
      have known. Eighteen percent of practice nurses reported uptake of supervision
      through the local scheme. The benefits of involvement were professional
      development tailored to individual learning needs and regular opportunities to
      share work-related problems with peers; about a third reported benefits for the
      practice as well. The existing availability of peer support and time needed to
      undertake clinical supervision were common reasons given for non-involvement in
      the scheme. Misconceptions about the purpose of clinical supervision presented
      further obstacles. At follow-up over half of the practice nurses remained
      undecided about their future involvement in the scheme. If the benefits
      associated with clinical supervision are to be realized, the obstacles that
      currrently hinder practice nurses' involvement need addressing.

PMID- 11820230
TI  - Intensive care nurses' experiences of caring for brain dead organ donor patients.
AB  - This study was designed to identify the feelings and experiences of critical care
      nurses who have been involved in nursing brain dead patients prior to organ
      donation. The purpose of the study was to generate knowledge which informs the
      discipline of nursing. A number of themes relating to nurses' experiences of
      caring for brain dead organ donor patients were uncovered in this interpretative
      study. Overall, caring for patients who are diagnosed as brain dead is a
      challenging experience for nurses and they are intensely involved in a search for
      meaning in each event. The interpretative analysis in this study has revealed a
      range of meanings articulated by the nurses involved. However, the primary focus
      of care--as identified by the participating nurses--was the donor family.

PMID- 11820231
TI  - Nurses' first encounters with parents of new-born children--public health nurses'
      views of a good meeting.
AB  - The nurse's view of the first meeting with parents of new-born children ma have
      consequences for the quality of future contact. A good start will lay a soli
      foundation for a lasting relationship, and have an affect on the nurse's work to
      support parents and children and to promote health. We do not know wha nurses
      mean by a 'good meeting'. The aim of this study was to discover how nurses view
      the first meeting as a general preventive measure aimed at all parents and their
      new-born children. Four focus groups interviews were held with nurses from
      different primary health care areas in the county of Skane, southernmost Sweden.
      Analysis of the content in the transcribed interview texts disclosed eight
      subcategories: good contact/reciprocal relationship; willingness to listen;
      guest/ equal roles; time/peace and quiet; the family in its environment; socio
      cultural aspects; confirmation/support; and individual advice. Three categories
      were established: creating trust; creating a supportive climate; and creating a
      picture of the family's life situation. The home visit was seen as an important
      way to establish trust and obtain a picture of the family's life situation, which
      was in turn essential for creating a supportive climate.

PMID- 11820232
TI  - A review of the psychosocial predictors of help-seeking behaviour and impact on
      quality of life in people with urinary incontinence.
AB  - Although urinary incontinence is common and can have a substantial impact on an
      individual's quality of life, few people seek help for this symptom. This paper
      examines a theoretical framework proposed by Shaw (1999) as a possible
      explanatory model for help-seeking and the impact of incontinence on a person's
      quality of life. Although aetiology and symptom severity are important predictors
      of behaviour and impact of symptoms, they did not explain all the variation and
      so other predictors proposed by the model were explored. Appraisals of illness
      and coping resources were found to be important moderating factors between the
      experience of symptoms and subsequent behaviour and outcome in urinary
      incontinence. In the appraisal of symptoms, lack of knowledge of the causes and
      treatments of urinary incontinence can be a barrier to help-seeking and
      successful outcome. Other factors such as personality, group differences, and
      social support can contribute to the appraisal process. Areas for future research
      and implications for clinical practice are discussed.

PMID- 11820233
TI  - The significance of empowerment for perceptions of control: a case study of a
      home for older people.

PMID- 11820234
TI  - Works of art: a complement to theoretical knowledge when teaching nursing care.
AB  - Visual art dialogues were used in student nurses' education as a teaching and
      learning complement to theoretical knowledge of nursing care. An intervention
      group as well as a control group discussed what was characteristic of good
      nursing care. The control group was used to control for the effects of visual art
      dialogues in the intervention group. The study was undertaken at two university
      colleges of health sciences in Sweden. Data were collected from student nurses (n
      = 267) during their first year of study. The Wheel Questionnaire was used in the
      intervention group and control group. It measured three aspects of student
      nurses' perception of nursing situations: structure, the extent of emotional
      involvement, and motivation. The results showed statistical differences (one way
      ANOVA) between the intervention group in which visual art dialogues were
      implemented and the control group. Students in the intervention group, compared
      to the control group, were more structured, motivated and emotionally balanced
      when they expressed the elements most typical of good nursing care. They showed
      personal readiness in caring situations.

PMID- 11820235
TI  - Defining the nursing contribution to patient outcome: lessons from a review of
      the literature examining nursing outcomes, skill mix and changing roles.
AB  - A review of the evidence to define the nursing contribution to patient outcome is
      presented. The review relies on work related to nursing sensitive outcomes, skill
      mix and changing roles. Methodological difficulties associated with these studies
      are highlighted. Areas requiring further research are discussed. It is suggested
      that experimental evidence is not always appropriate, when attempting to describe
      nursing activity. The authors advocate that new methodologies, in particular
      practitioner-centred research, are needed to unpack the nature of nursing.

PMID- 11820236
TI  - Clinical role clarification: using the Delphi method to establish similarities
      and differences between nurse practitioners and clinical nurse specialists.
AB  - This article is based on the Department of Health's (England) funded pluralistic
      evaluation of Nurse Practitioner preparation, 'Realizing Specialist & Advanced
      Nursing Practice: establishing the parameters of and identifying competencies for
      "Nurse Practitioner" roles and evaluating programmes of preparation' (RSANP).
      During this 27-month project, which began in 1996, one of the research methods
      used, the Delphi study, was aimed at reaching a consensus of views amongst nurses
      in clinical practice, educators, purchasers, providers and representatives of
      statutory and professional bodies on the parameters and competencies desirable
      for the Nurse Practitioner role. The agreed competencies were then used as one
      measure of the appropriateness of various programmes used to prepare Nurse
      Practitioners. Of the competencies required for the role, the majority are
      'nursing' competencies and are the same as those required for the Clinical Nurse
      Specialist role. However, for both Clinical Nurse Specialists and Nurse
      Practitioners, these are practised at a 'higher level'. Other competencies needed
      for the Nurse Practitioner role relate to the knowledge and skills required to
      assess, diagnose and determine nursing and medical management of a patient and to
      evaluate that management. Data indicated, however, that even these competencies
      were being used by some Clinical Nurse Specialists. Final analysis enabled the
      identification of the two roles with the use of a 'Typology of Named Clinical
      Nursing Roles'.

PMID- 11820237
TI  - Searching for sustainable change.
AB  - Change in nursing practice has been dogged by factors which have been perceived
      to be outside the autonomy of nurses. Consequently, projects have been initiated
      which have then faltered or even ceased altogether This paper reports on an
      action research study that was carried out in Newcastle from 1997 to 1999 and
      used the process within a focus group setting to rekindle and sustain an
      innovative change. The aim of the study was to look at staff perceptions
      surrounding development of the practice of self-administration of medication for
      patients. The findings support the view that all disciplines need to be involved
      in health service change. Health service employees should have a knowledge of the
      theory associated with the change process and be open about their views of
      proposed alterations in practice. They also need to have a sense of
      dissatisfaction with the present, a clear outline of what the problem is and the
      direction which they intend to take. Change involves many complex issues. It
      should be worked through from a bottom-up approach and consist of repeated
      evaluation exercises which are akin to a cyclical strategy and include a
      reflective process.

PMID- 11820238
TI  - Energy and nutrient intake of patients in acute care.
AB  - There have been numerous reports that the nutritional intake of many hospitalized
      patients is sub-optimal, but there is little published information about
      patients' diets in Australian hospitals. In this study, the nutritional intake of
      patients in general medical wards of an Australian acute care hospital was
      assessed. Although the hospital diet can provide adequate energy and nutrients,
      many patients may not consume sufficient food to meet their needs. The estimated
      energy intake of about one-third of patients was very low, and vitamin C, calcium
      and zinc intakes were also of concern. The implications are discussed and
      recommendations for improved nutritional care are suggested.

PMID- 11820239
TI  - Hospital care pathways for patients with schizophrenia.
AB  - Greater emphasis is being placed on reducing clinical variation in managing
      patient groups in the reformed National Health Service (NHS) in the United
      Kingdom (UK). The use of a care pathway to enable greater control over the
      process and quality of care will be explored for patients suffering from
      schizophrenia. The paper addresses three main factors for the development of care
      pathways for people suffering from schizophrenia: predictability of the illness;
      nature of standardized care; and role autonomy. It is argued that the diagnosis
      of schizophrenia does not lend itself easily to predicting care and treatment
      within a care pathway framework. However, a care pathway may bring other
      benefits, such as standardized care and a greater control over the delivery of
      care. Development and implementation of hospital care pathways require extensiv
      research. Qualitative research directions are advocated due to the possib
      difficulties of conducting an experimental study.

PMID- 11820240
TI  - Professionals' perceptions of children's participation in decision making in
      healthcare.
AB  - The purpose of this study was to identify factors of importance for children's
      participation in medical and nursing care. A method close to the critical
      incident technique was used. A total of 92 stories told by staff and containing
      different levels of children's participation in decision making were analysed.
      The factors affecting children's participation in decision making were grouped
      into six categories: the child's protest, the child's age and maturity, the role
      of parents, attitudes of staff, the time factor and alternative solutions to the
      problem. This study shows that in certain cases children can affect their
      situation, bus also that violating actions are performed on children.

PMID- 11820241
TI  - Developing a unified language for children's nurses, children and their families
      in the United Kingdom.
AB  - This paper presents a taxonomy of Infant, Child and Adolescent (ICA) nursing
      diagnoses and clinical outcomes that has been developed with the co-operation of
      nurses caring for children in the United Kingdom. Three focus group interviews
      were conducted in one acute care NHS trust in London (referred to as the host
      trust in this paper) in 1998/99, in which participants were asked to consider
      nursing and family factors relevant for identifying and providing care. A total
      of 28 ICA diagnoses, including definitions, defining characteristics and
      outcomes, were identified for clinical testing and included in the ICA taxonomy.
      The ICA diagnostic labels and outcomes for care were further tested for their
      relevance for clinical practice in a Delphi Survey carried out in 1999 and their
      use in clinical practice began in 1999. This research augments the findings from
      an initial Delphi survey carried out in 1993 and case study research in 1996. The
      previous research initiated the development of a unified language for children's
      nurses, children and their families, to aid communication and decision-making.
      Implications of this and future research for clinical practice, nationally and
      internationally, are also discussed.

PMID- 11820242
TI  - Student nurses' perception of independence of supervision during clinical nursing
      practice.
AB  - The purposes of this longitudinal study were to examine Swedish student nurses'
      perceptions of independence and to explore to what extent the students had had
      opportunities to practise different tasks during clinical practice. Data were
      collected on weekly self-assessment forms during the first and final clinical
      courses of a 3-year nursing programme for 60 and the remaining 48 students,
      respectively. The majority of the students rated themselves as being independent
      of supervision to a great extent both at the beginning and throughout the
      clinical courses. Some students reported no or few opportunities to practise
      certain tasks during both courses. Factors that may have influenced the students'
      perception of independence are discussed, such as preparation before the clinical
      courses and the importance students gave to certain tasks. Clinical practice
      should be carefully planned and individualized to facilitat students'
      opportunities to practise different tasks.

PMID- 11820243
TI  - The experience of practice development: an exploratory telephone interview study.
AB  - Practice development is a widely used term within British nursing. However, there
      is a lack of consistency and clarity in the way that the term is used. A small
      scale qualitative telephone interview study was therefore conceived to explore
      practitioners' views of practice development. Qualitative telephone interviews
      were carried out with 26 nurses working in a range of settings and roles around
      the UK. Informants reported varying degrees of awareness of practice development
      roles and activities ranging from little awareness to being closely involved.
      Most informants seemed to place more emphasis on issues of personal development
      and educational aspects of practice development than is found in the literature.
      Practice development staff were seen as having a range of functions ranging from
      working with individual practitioners to the co-ordination of education and
      training within an organization. The credibility of practice development staff
      was closely related to their clinical experience and ability.

PMID- 11820244
TI  - [Medical interests in gymnastics and athletics].
AB  - Since time immemorial authors have noticed the usefulness of physical activity.
      In the 18th century C von Linne was a spokesman for bodily exercise, and in the
      beginning of the 19th century P. H . Ling shaped the Swedish gymnastics and
      founded the Gymnastiska Centralinstitutet in 1813. He aimed at harmonious bodies
      according to the models of the classic antiquity. Many physicians, I. and F.
      Holmgren saw the value of the gymnastics. Completing the Ling gymnastics, there
      was a growing interest in physical performance, i.e., athletics. Above all, the
      contributions of the officer V. Balck, culminating at the olympic games in
      Stockholm 1912, made athletics a national movement. Since 1913 it receives an
      annual economic support from the state. Some physicians feared from overexertion
      in athletics but they appreciated physical performance. However, they demanded
      that you should be wholly full-grown prior to great exortions. An important part
      of the Ling program was remedial gymnastics which was more and more estimated
      after P. Haglund had asserted its value. T. Sjostrand's studies became a good
      basis for evaluating the effect of physical training in both healthy and sick
      persons. It was not until the 1950s that the first studies, later confirmed, gave
      holds for the view that physical training was good for public health. But the
      average life span does not seem to be influenced by physical activities. Now and
      then training had earlier been used as therapy for disparate sorts of diseases
      but most rationally for disturbed functions of the locomotor system. Training
      became an important part of medical rehabilitation only after the second world
      war. Gymnastics and athletics at school have always had a solid support by
      physicians. The subject has nowadays so few hours that it cannot result in safe
      training habits for the future.

PMID- 11820245
TI  - [Swedish research in hypertension].
AB  - In Sweden, research in hypertension has been on-going since the early 1920's when
      Eskil Kylin was the first to describe hypertension as part of a metabolic
      cardiovascular syndrome. Later on several other researchers and clinicians have
      contributed to the development of medical understanding of hypertension and its
      treatment. Bertil Hood was the one who started modern drug therapy for malignant
      hypertension in 1950 when hexamethonium was used, which was a life-saving drug
      but with many serious adverse reactions. Later on other drugs have been developed
      many of them first tested in smaller haemodynamic studies before used in clinical
      trials. Some of these smaller studies were initiated by Lars Werko and his
      colleagues. In recent years Swedish researchers have made great contributions in
      hypertension research, e.g. Bjorn Folkow for studies regarding arterial wall
      modelling in hypertension, and Lennart Hansson for initiating large-scale
      randomised clinical trials in middle-aged and elderly hypertensive patients. In
      spite of the fact that hypertensive patients constitute the largest patient group
      of all, with currently 700.000 treated patients in Sweden, it is still not well
      established which therapy and other interventions are the most beneficial and
      cost-effective for long-term treatment. Swedish research in hypertension is
      therefore ongoing and supported by the Swedish Hypertension Society for which
      Peter Nilsson is the current patient.

PMID- 11820247
TI  - Cardiac resynchronization therapy.

PMID- 11820246
TI  - [Santiago Ramon y Cajal and neurobiology].
AB  - In 2001 the centennial of the first Nobel Prizes is celebrated. This essay, which
      portrays the Nobel Laureate in Physiology or Medicine in 1906 Don Santiago Ramon
      y Cajal, should be seen as a contribution to that celebration. The aim of the
      essay is to present one of the founders of modern neuroscience and greatest
      scientists of all time, his life history, personality, working methods and
      driving forces as well as his scientific contributions. The title of the essay
      "Ideas -- like the white water-lily - flourish only in tranquil waters" is a
      quotation from Ramon y Cajal which characterizes him very well as a scientist. He
      was extremely productive, he made fundamental contributions to a number of fields
      within neurobiology with a very few mistakes, and he did it all by himself.

PMID- 11820248
TI  - Online health companies announce new set of ethics and privacy guidelines.

PMID- 11820249
TI  - Two societies address financial conflicts of interest in gene therapy trials.

PMID- 11820250
TI  - Pediatric surgery.

PMID- 11820251
TI  - Additional criteria and procedures for classifying over-the-counter drugs as
      generally recognized as safe and effective and not misbranded. Final rule.
AB  - The Food and Drug Administration (FDA) is issuing a final rule establishing
      additional criteria and procedures by which over-the- counter (OTC) conditions
      may become eligible for consideration in the OTC drug monograph system. The
      criteria and procedures address how OTC drugs initially marketed in the United
      States after the OTC drug review began in 1972, and OTC drugs without any U.S.
      marketing experience, can meet the statutory definition of marketing to a
      "material extent" and "for a material time" and become eligible. If found
      eligible, the condition would be evaluated for general recognition of safety and
      effectiveness in accordance with FDA's OTC drug monograph regulations. FDA is
      also changing the current OTC drug monograph procedures to streamline the process
      and provide additional information in the review.

PMID- 11820252
TI  - Medical devices; gastroenterology-urology devices; classification of the
      ingestible telemetric gastrointestinal capsule imaging system. Final rule.
AB  - The Food and Drug Administration (FDA) is classifying the ingestible telemetric
      gastrointestinal capsule imaging system device into class II (special controls).
      The special controls that will apply to this device are set forth below. 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.

PMID- 11820253
TI  - Diseases specific to radiation-exposed veterans. Final rule.
AB  - The Department of Veterans Affairs (VA) is amending its adjudication regulations
      concerning presumptive service connection for certain diseases for veterans who
      participated in radiation-risk activities during active service or while members
      of reserve components during active duty for training or inactive duty training.
      This amendment adds cancers of the bone, brain, colon, lung, and ovary to the
      list of diseases which may be presumptively service connected and amends the
      definition of the term "radiation-risk activity." The intended effect of this
      amendment is to ensure that veterans who may have been exposed to radiation
      during military service do not have a higher burden of proof than civilians
      exposed to ionizing radiation who may be entitled to compensation for these
      cancers under comparable Federal statutes.

PMID- 11820255
TI  - Candida africana sp. nov., a new human pathogen or a variant of Candida albicans?
AB  - Atypical Candida strains were isolated from patients in Madagascar, Angola and
      Germany. These isolates were slow growing and were unable to produce
      chlamydospores. They had atypical carbohydrate assimilation profiles. All strains
      were unable to assimilate the amino sugars N-acteylglucosamine and glucosamine as
      well as the disaccharide trehalose and the organic acid DL-lactate. They were
      germ-tube-positive in serum, but only some of these organisms produced
      pseudohyphae after a long incubation. As shown by Fourier transform infrared
      spectroscopy the atypical Candida isolates clustered as a monophyletic group
      different from C. albicans and C. dubliniensis. All strains belonged to C.
      albicans serotype B. Considering all data presented here, this group of Candida
      strains differs from any other known member of the genus Candida. Therefore, it
      is suggested to represent a new species within the genus Candida for which the
      name Candida africana is proposed.

PMID- 11820254
TI  - Functional associations of proteins in entire genomes by means of exhaustive
      detection of gene fusions.
AB  - BACKGROUND: It has recently been shown that the detection of gene fusion events
      across genomes can be used for predicting functional associations of proteins,
      including physical interaction or complex formation. To obtain such predictions
      we have made an exhaustive search for gene fusion events within 24 available
      completely sequenced genomes. RESULTS: Each genome was used as a query against
      the remaining 23 complete genomes to detect gene fusion events. Using an
      improved, fully automatic protocol, a total of 7,224 single-domain proteins that
      are components of gene fusions in other genomes were detected, many of which were
      identified for the first time. The total number of predicted pairwise functional
      associations is 39,730 for all genomes. Component pairs were identified by virtue
      of their similarity to 2,365 multidomain composite proteins. We also show for the
      first time that gene fusion is a complex evolutionary process with a number of
      contributory factors, including paralogy, genome size and phylogenetic distance.
      On average, 9% of genes in a given genome appear to code for single-domain,
      component proteins predicted to be functionally associated. These proteins are
      detected by an additional 4% of genes that code for fused, composite proteins.
      CONCLUSIONS: These results provide an exhaustive set of functionally associated
      genes and also delineate the power of fusion analysis for the prediction of
      protein interactions.

PMID- 11820256
TI  - Trends in species causing fungaemia in a tertiary care medical centre over 12
      years.
AB  - Trends in the species of yeast causing fungaemia over a 12-year period at a large
      tertiary care medical centre were reviewed. A total of 966 unique episodes of
      fungaemia occurred in 898 patients. There was an overall trend toward fewer
      fungaemic episodes due to Candida albicans and more due to Candida glabrata and
      Candida parapsilosis. However, C. albicans remained the predominant species
      causing fungaemia, and the proportion due to other species varied from year to
      year. Candida glabrata was disproportionately isolated from older adults, whereas
      C. parapsilosis was common among neonates and infants. The trends of increasing
      isolation of C. glabrata and decreasing isolation of C. albicans were associated
      with increasing usage of fluconazole, but changes in the proportion of fungaemias
      due to other species appeared to have no association with fluconazole usage.

PMID- 11820257
TI  - Incidence of endomycoses in autopsy material.
AB  - From 1970 to 1993, 93 endomycoses confirmed by postmortem examination were
      diagnosed in the autopsy material of the Berlin Charite, a large hospital with an
      average of 1,500 Hospital beds and maximum medical care. These comprised 51
      candidoses (54.8%), 24 aspergilloses (36.5%), five cryptococcoses (5.4%), one
      zygomycosis, one trichosporosis and one coccidioidomycosis. This corresponded to
      0.7% of the 13,275 deceased persons autopsied during this period. The frequency
      of autopsy was 85.3%. In 3,770 cases (2,418 adults and 1,352 children), brain
      dissection was performed. An adequate clinical putative diagnosis was made in
      only six out of 28 patients (18 adults, 10 children) with histologically
      confirmed cerebral mycosis: 11 candidoses (39.3%), 10 aspergilloses (35.7%) five
      cryptococcosis (17.8%), one trichosporosis and one coccidioidomycosis. About 80%
      of the mycoses of the CNS thus remained undetected while the patients were alive.
      The observations made in the present paper underscore the importance of clinical
      autopsy in endomycoses.

PMID- 11820258
TI  - Liposomal amphotericin B for prophylaxis of invasive fungal infections in high
      risk paediatric patients with chemotherapy-related neutropenia: interim analysis
      of a prospective study.
AB  - Invasive fungal infections (IFI) are a major cause of morbidity and mortality in
      patients with cancer. A retrospective analysis of children with cancer at high
      risk for IFI treated at Munster University Hospital showed that the incidence
      (7.4% vs. 1.8%) and lethality (28.1% vs. 0) of documented IFI were lower in
      patients receiving systemic antifungal prophylaxis with liposomal amphotericin B
      (l-AmB) in comparison to a historical control group. To determine whether this
      decline in incidence and lethality was due to antifungal prophylaxis or was
      produced by advances in diagnostic procedures and early empirical antifungal
      therapy, a prospective study was initiated. Patients in the prophylaxis arm
      received thrice-weekly 1 mg kg(-1) body weight l-AmB, whilst patients in the
      early intervention arm received no prophylaxis. Diagnostic procedures and
      antifungal therapy for suspected or proven IFI were initiated as clinically
      indicated for all patients. The primary endpoint of the study was the incidence
      of IFI. Secondary endpoints were the use of therapeutic doses of l-AmB, the
      safety of prophylactic l-AmB, and the total consumption of l-AmB for antifungal
      therapy. The interim analysis after 1 year showed no differences between the two
      approaches with respect to the incidence of IFI and to safety issues.

PMID- 11820259
TI  - Adherence of Aspergillus species to soft contact lenses and attempts to inhibit
      the adherence.
AB  - The aim of this research was to assess the adherence of various Aspergillus
      species (A. niger, A. fumigatus, A. flavus) to contact lenses with different
      water content and to attempt to inhibit the adherence of Aspergillus spp. to the
      contact lenses by a chitin derivative (CSE). Adherence of Aspergillus spp. to
      lenses with higher water content was greater. Differences were found between the
      adherence levels of various Aspergillus species to contact lenses with different
      water content. CSE significantly inhibits the adherence in vitro of A. niger, A.
      fumigatus and A. flavus to soft contact lenses. These findings suggest a
      possibility for prevention of fungal ocular infections caused by Aspergillus spp.
      in wearers of contact lenses.

PMID- 11820260
TI  - Otomycosis: prevalence, clinical symptoms, therapeutic procedure.
AB  - Local lesions observed in otitis, create favourable conditions for the growth of
      fungi and development of mycoses both in the external and middle ear, as well as
      in post-operative cavities, especially in cases of open-type surgery. The
      objective of this study was: (1) to determine the prevalence of mycotic
      infections in inflammatory conditions of the ear; (2) to evaluate the
      relationship between the presence of fungi and clinical symptoms of inflammation;
      and (3) to construct a model of therapeutic procedure. The study concerned 345
      individuals, including 295 patients (381 ears) who presented with symptoms of
      otitis. The mycological examinations revealed presence of fungi in 30.4% cases
      (116 ears). Positive culture results were obtained predominantly in patients with
      post-operative suppuration (52.8%). Otomycosis was more often associated with
      fungi of the genus Candida (3/5) than with fungi of the genus Aspergillus (2/5).
      The analysis of symptoms in otomycoses showed that in bacteria-induced otitis,
      pruritus, discharge, post-operative defective hearing and headaches are most
      common; the analysis of signs showed that reddened epidermis and lining of the
      tympanic cavity are statistically more frequent. The therapeutic protocol adopted
      in otomycoses yields good results: 89%--complete cure.

PMID- 11820261
TI  - Phenotypic characterization of Microsporum canis isolated from cats and dogs.
AB  - To characterize strains of Microsporum canis that infect dogs and cats in Sao
      Paulo city, 30 isolates of this dermatophyte were tested for their ability to
      assimilate carbon and nitrogen sources, for proteinase and phospholipase
      secretion, for susceptibility to yeast killer toxins, and for susceptibility to
      the antifungals fluconazole, ketoconazole, itraconazole, 5-fluorocytosine and
      amphotericin B, in E test. All samples assimilated the nitrogen sources
      asparagine, ammonium sulphate, urea and sodium nitrate, as well as the carbon
      sources inulin, mannitol, trehalose, meso-erythritol, maltose, mannose, sorbitol,
      cellobiose, fructose and dextrin. Not all the samples assimilated adonitol,
      galactose, arabinose, rhamnose, raffinose, melibiose, ribose and sucrose, and
      none of them was capable of growing with dulcitol, lactose, or xylose as the only
      carbon source. Proteinase and phospholipase secretion was observed for most
      isolates. In the test of yeast killer toxin, 10 types could be identified, with
      four types exclusively observed in isolates from dogs and two types exclusively
      observed in isolates from cats. In the E test, all isolates were found to be
      resistant to the fluconazole and 5-fluorocytosine, while they were variably
      sensitive to amphotericin B, ketoconazole and itraconazole. When the data were
      submitted to the qualitative analysis in the matrix distance program FITOPAC, the
      similarity of the isolates could be assessed.

PMID- 11820262
TI  - Evaluation of lymphocytes subpopulations and natural killer cells in peripheral
      blood of patients treated for dermatophyte onychomycosis.
AB  - Thirty-five patients with dermatophyte onychomycosis caused by Trichophyton
      rubrum, T. mentagrophytes var. granulosum, T. tonsurans and Epidermophyton
      floccosum were examined before treatment and 27 of these patients were examined
      again when they came to the control check up 3 months after completion of
      treatment. The immunological investigations, including evaluation of
      immunological competence, were performed in vivo through the determination of
      lymphoid cell immunophenotype by a flow cytometry technique. The quantitative
      composition of basic lymphocyte subpopulations and natural killer cells in the
      peripheral blood of 35 patients before the treatment was compared with a control
      group of 20 individuals. Statistically significant differences in the percentages
      of CD3+ T lymphocytes (P<0.05), T helper lymphocytes (CD4+) (P<0.05) and
      activated T lymphocytes (CD3+/HLA-DR+) (P<0.05) were obtained. In the control
      check-up examinations of 27 patients 3 months after completion of treatment, in
      comparison with the control group of 20 healthy individuals, highly statistically
      significant differences in percehtages of T lymphocytes (CD3+) (P<0.001) and T
      helper lymphocytes (CD4+) (P<0.01) were obtained. In five of these 27 patients
      the treatment resulted in failure. Comparing the group of 22 recovered patients
      with these five patients in whom the treatment result was failure, the only
      statistically significant difference obtained before as well as after the
      treatment was in B lymphocytes (CD19+) percentage (P<0.05). The results obtained
      confirm that impairments of the patients' cellular immunity are crucial factors
      influencing the course and results of treatment in dermatophyte onychomycosis.

PMID- 11820263
TI  - Dermatophytoses in Prague, Czech Republic, between 1987 and 1998.
AB  - Over a 12-year period, from 1987 to 1998, the spectrum of aetiological agents
      isolated from 11208 patients (6265 females and 4943 males) suspected of having
      dermatomycosis was analysed in the mycological laboratory of the Department of
      Dermatology, Charles University, Prague. The most frequently examined locations
      were toenails (34.9%), feet (15.6%), fingernails (12.8%), toe webs (11%), trunk
      (10%) and hands (8.7%). Dermatophytes were isolated from 5605 (30.2%) of all
      18528 samples examined. Among dermatophytes, the most common infectious agent was
      Trichophyton rubrum (90.2%) followed by Trichophyton mentagrophytes (6.6%),
      Microsporum canis (1.8%) and Epidermophyton floccosum (1.4%). Trichophyton
      verrucosum, Microsporum persicolor and Microsporum gypseum were rare. During this
      12-year period the pattern of aetiological agents of dermatomycoses in Prague was
      relatively stable.

PMID- 11820264
TI  - Case report. Recurrence of increased intracranial pressure with antiretroviral
      therapy in an AIDS patient with cryptococcal meningitis.
AB  - We present the case of an AIDS patient with cryptococcal meningitis who, after an
      excellent clinical and mycological response to antifungal therapy, developed an
      exacerbation of signs and symptoms, including elevated intracranial pressure and
      an increase in cerebrospinal fluid cryptococcal antigen and white blood cells,
      following the initiation of highly active antiretroviral therapy (HAART).
      Cultures yielded no growth and the patient responded to repeated lumbar punctures
      without changing or intensifying antifungal therapy. To our knowledge, this is
      the first report of symptomatic elevated intracranial pressure occurring during
      HAART-related immune recovery in a patient with cryptococcal meningitis.
      Exacerbation of symptoms does not necessarily reflect mycological failure that
      requires a change in antifungal therapy, but may relate to acutely increased
      intracranial pressure that will respond to simple measures, such as repeated
      lumbar punctures.

PMID- 11820265
TI  - Case report. Fungaemia due to Penicillium piceum, a member of the Penicillium
      marneffei complex.
AB  - Due to the inability of most Penicillium species to grow at 37 degrees C,
      systemic non-marneffei infections are very rare in the human host. We describe a
      case of fungemia due to Penicillium piceum in a female patient, who died a few
      days after repeated isolation of this fungus from blood cultures. The species is
      a member of the section Biverticillata of Penicillium, as was confirmed by rDNA
      Internal Transcribed Spacer (ITS) sequence data, and hence may share virulence
      factors with P. marneffei.

PMID- 11820266
TI  - Case report. Disseminated infection of Blastoschizomyces capitatus in a patient
      with acute myelocytic leukaemia.
AB  - Blastoschizomyces capitatus infection in a 48-year-old man with acute myelocytic
      leukaemia is reported. A multiorgan involvement and fulminant course of the
      fungal infection resulted in the patient's death despite fluconazole prophylaxis,
      therapy with amphotericin B and administration of granulocyte colony-stimulating
      factor. Predisposing factors to the infection, clinical relevance of surveillance
      strains and in vitro antifungal susceptibility testing are discussed.

PMID- 11820267
TI  - Case report. Successful treatment of cutaneous Paecilomyces lilacinus infection
      with oral itraconazole in an immune competent host.
AB  - A 59-year-old woman presented to us with an eight-month history of Paecilomyces
      lilacinus soft tissue infection. She was treated with a six-month course of oral
      itraconazole. The lesion resolved fully without the need for adjunctive surgery.
      Susceptibility testing confirmed susceptibility to itraconazole. This is the
      second case of confirmed P. lilacinus soft tissue infection in an immunocompetent
      host treated with oral itraconazole alone.

PMID- 11820268
TI  - Case report. Erythrasmoid pityriasis versicolor.
AB  - A 50-year-old Caucasian man with pityriasis versicolor that was localized almost
      exclusively in the inguinal folds and was characterized by lesions clinically
      superimposable on those of erythrasma is described. Due to these clinical
      characteristics, it is proposed that this variety of pityriasis versicolor is
      defined as 'erythrasmoid'.

PMID- 11820269
TI  - Case report. First isolation of Trichosporon domesticum from a cat.
AB  - The present study deals with the first isolation of Trichosporon domesticum from
      the urine of a cat with chronic cystitis. A 5-year-old domestic short hair cat
      weighing 5.6 kg was referred to an animal hospital with the chief complaint of
      haematuria having persisted for 3 weeks. The isolate was identified as T.
      domesticum, confirming the result of mycological examination by molecular
      analysis.

PMID- 11820270
TI  - Determination of aldehydes in drinking water using pentafluorobenzylhydroxylamine
      derivatization and solid-phase microextraction.
AB  - A headspace solid-phase microextraction (HS-SPME) procedure followed by gas
      chromatography and electron capture detection (GC-ECD) has been developed for the
      determination of aldehydes in drinking water samples at microg/l concentrations.
      A previous derivatization with o-(2,3,4,5,6-pentafluorobenzyl)hydroxylamine
      hydrochloride (PFBHA) was performed due to the high polarity and instability of
      these ozonation by-products. Several SPME coatings were tested and the
      divinylbenzene-polydimethylsiloxane (DVB-PDMS) coating in being the most suitable
      for the determination of these analytes. Experimental SPME parameters such as
      selection of coating, sample volume, addition of salt, extraction time and
      temperature of desorption were studied. Analytical parameters such as precision,
      linearity and detection limits were also determined. HS-SPME was compared to
      liquid-liquid microextraction (proposed in US Environmental Protection Agency
      Method 556) by analyzing spiked water samples; a good agreement between results
      obtained with both techniques was observed. Finally, aldehydes formed at the
      Barcelona water treatment plant (N.E. Spain) were determined at levels of 0.1-0.5
      microg/l. As a conclusion, HS-SPME is a powerful tool for determining ozonation
      by-products in treated water.

PMID- 11820271
TI  - What are we determining using gas chromatographic multiresidue methods:
      tralomethrin or deltamethrin?
AB  - The analytical behaviour of the relatively new pyrethroid insecticide
      tralomethrin has been evaluated by using gas chromatography (GC) with electron
      capture and mass spectrometry (MS) detectors, and liquid chromatography (LC)
      atmospheric pressure ionization mass spectrometry with electrospray interfacing.
      Under the GC conditions commonly used in pesticide residue analysis, it was found
      that tralomethrin is transformed into deltamethrin (in a reproducible way) in the
      injector port of the GC system. Results obtained in this work indicate that the
      GC multiresidue methodologies routinely applied in the analysis of pyrethroid
      pesticides in foods cannot distinguish between these two pesticides, and the
      chromatographic signal obtained at the retention time of
      deltamethrin/tralomethrin can be really quantified as either deltamethrin or
      tralomethrin, including when it is confirmed as deltamethrin by MS. Under the LC
      MS conditions assessed in this work, deltamethrin and the two diasteroisomers of
      tralomethrin were well separated and identified.

PMID- 11820272
TI  - Pressurised hot water extraction coupled on-line with liquid chromatography-gas
      chromatography for the determination of brominated flame retardants in sediment
      samples.
AB  - Pressurised hot water extraction (PHWE) was coupled on-line with liquid
      chromatography-gas chromatography (LC-GC) to determine brominated flame
      retardants in sediment samples. After extraction with pressurised hot water the
      analytes were adsorbed in a solid-phase trap. The trap was dried with nitrogen
      and the analytes were eluted to the LC column, where the extract was cleaned,
      concentrated and fractionated before transfer to the GC system. The fraction
      containing the brominated flame retardants was transferred to the GC system via
      an on-column interface. The PHWE-LC-GC method was linear from 0.0125 to 2.5
      microg with limits of detection in the range 0.70-1.41 ng/g and limits of
      quantification 6.16-12.33 ng/g.

PMID- 11820273
TI  - Classification of Nebbiolo-based wines from Piedmont (Italy) by means of solid
      phase microextraction-gas chromatography-mass spectrometry of volatile compounds.
AB  - Sixty-eight samples of wines from Piedmont (Italy) were analysed to determine
      their content of volatile compounds, using the solid-phase microextraction (SPME)
      technique coupled with gas chromatography-mass spectrometry (GC-MS). Samples were
      from five groups of wines: Barolo, Barbaresco, Nebbiolo d'Alba, Roero and Langhe
      Nebbiolo, all produced from the Nebbiolo grape in the Langhe and Roero areas
      (province of Cuneo, Piedmont) but differing in vintage (respectively, 3 years, 2
      years, 1 year, 8 months and few months) and production zone. Thirty-five analytes
      were identified; peak area data, corrected for internal standard, were used for
      pattern recognition treatments. Principal components analysis, hierarchical
      cluster analysis, Kohonen self organising map, stepwise linear discriminant
      analysis and soft independent modelling of class analogy were applied to the
      data, revealing a good separation between the five groups. A main factor,
      strictly connected to wine vintage, was identified and found to be related to
      some analytes.

PMID- 11820274
TI  - Nonlinear analysis of dynamic binding in affinity capillary electrophoresis
      demonstrated for inclusion complexes of beta-cyclodextrin.
AB  - The stability of the molecular host-guest inclusion complexes of beta
      cyclodextrin with benzoate and four different hydroxybenzoates is investigated.
      For the measurement of the binding constants an experimental method is devised
      that is based on affinity capillary electrophoresis (ACE) with indirect UV
      absorbance detection. We derive an explicit equation for effective mobilities in
      ACE experiments without violation of rigorous mass balance. This equation is
      employed in the nonlinear least-squares analyses of the experimental data
      yielding binding constants of 48+/-2 M(-1) for benzoate, 299+/-38 M(-1) for 2
      hydroxybenzoate, 37+/-1 M(-1) for 3-hydroxybenzoate, 228+/-9 M(-1) for 4
      hydroxybenzoate, and 895+/-110 M(-1) in the case of 2,4-dihydroxybenzoate.

PMID- 11820275
TI  - On-line direct determination of the second virial coefficient of a natural
      polysaccharide using size-exclusion chromatography and multi-angle laser light
      scattering.
AB  - By combining a size-exclusion chromatographic (SEC) separation and an on-line
      multi-angle light scattering (MALLS) analysis, we have elaborated an original
      methodology permitting on-line direct determination of the second virial
      coefficient of molar mass fractions of polydisperse polysaccharides. By
      assimilating the SEC-MALLS data to a batch mode acquisition, we have obtained on
      line the complete Zimm plot of the eluted fractions, leading to knowledge of
      their weight-average molar mass Mw, radius of gyration r(g) and second virial
      coefficient A2. Our methodology was successfully applied to a iota carrageenan
      sample in LiCl 100 mM, EDTA 1 g/l.

PMID- 11820276
TI  - Behavior of packing materials in axially compressed chromatographic columns.
AB  - The behavior of a packing material (Luna C18 from Phenomenex, Torrance, CA, USA)
      was studied during the consolidation of a column bed under axial compression
      stress. The kinetics of this consolidation, the permeability and efficiency of
      the columns obtained, and the reproducibility of these column properties were
      measured under different conditions. The consolidation process and the column
      properties are considerably affected by the friction between the packing material
      in the bed and the column wall. Clear evidence of this wall effect was
      demonstrated. The apparent permeability of columns consolidated under the same
      axial stress increases with increasing column length. The apparent modulus of
      elasticity of the beds increases with increasing column length. The shear
      resistance between the packed bed and the column wall was measured for columns of
      different lengths. It increases rapidly with increasing bed length. The column
      efficiency for thiourea (unretained) and phenyloctane (retention factor, k'
      approximately 1) was much poorer after recompression than after the first
      compression. It depended little on the compression stress. The effect of the
      column length was small.

PMID- 11820277
TI  - Determination of active ingredients of Rhododendron dauricum L. by capillary
      electrophoresis with electrochemical detection.
AB  - High-performance capillary electrophoresis with electrochemical detection was
      employed to analyse active ingredients of Rhododendron dauricum L., an important
      crude herb frequently used in Chinese medicines. Farrerol, quercetin, syringic
      acid, vanillic acid, 4-hydroxybenzoic acid, protocatechuic acid are major
      important active ingredients. Operated in a wall-jet configuration, a 300-microm
      diameter carbon-disk electrode was used as the working electrode, which exhibits
      a good response at +950 mV (vs. saturated calomel electrodes) for six analytes.
      Under the optimum conditions, the analytes were baseline separated within 16 min
      in a borax buffer (pH 8.7). Notably, excellent linearity was obtained over two
      orders of magnitude with detection limits (S/N=3) ranged from 9 x 10(-7) to 3.0 x
      10(-6) M for all analytes. This method was successfully used in the analysis of
      Rhododendron dauricum L. with relatively simple extraction procedures, and the
      assay results were satisfactory.

PMID- 11820278
TI  - Fast analysis of flavonoids in plant extracts by liquid chromatography
      ultraviolet absorbance detection on poly(carboxylic acid)-coated silica and
      electrospray ionization tandem mass spectrometric detection.
AB  - A highly hydrophilic poly(7-oxonorbornene-5,6-dicarboxylic acid-block-norbornene)
      [=poly-(ONDCA-b-NBE)]-coated silica was investigated for the liquid
      chromatographic (LC) determination of flavonoids in plant extracts of complex
      biological origin using UV absorbance and mass spectrometric (MS) detection.
      Compared to the most commonly used octadecyl derivatized silica this sorbent
      allowed fast separations even at extreme pH values. Furthermore, UV absorbance
      and MS detection were evaluated. As we found, UV detection at 254 nm allows the
      determination of flavonoids down to the ng range with a linearity of R2>0.9906.
      For the more selective characterization the validated LC system was coupled to a
      quadrupole ion trap mass spectrometer via an electrospray ionization (ESI)
      interface. MS detection showed high linearity (R2>0.9904) for all investigated
      flavonoids. Due to the relatively high flow-rate of 1 ml/min the limits of
      detection were found in the lower-microg range. Collision induced dissociation
      was applied to obtain characteristic fragmentation fingerprints. Finally, the
      validated LC-ESI-MS-MS method demonstrated that this poly-(ONDCA-b-NBE)
      stationary phase allows fast characterization and quantitation in onion,
      elderflower blossom, lime blossom, St. John's Wort and red wine.

PMID- 11820279
TI  - Matrix effect and correction by standard addition in quantitative liquid
      chromatographic-mass spectrometric analysis of diarrhetic shellfish poisoning
      toxins.
AB  - An evaluation of the feasibility of liquid chromatography-mass spectrometry (LC
      MS) with atmospheric pressure ionization was made for quantitation of four
      diarrhetic shellfish poisoning toxins, okadaic acid, dinophysistoxin-1,
      pectenotoxin-6 and yessotoxin in scallops. When LC-MS was applied to the analysis
      of scallop extracts, large signal suppressions were observed due to coeluting
      substances from the column. To compensate for these matrix signal suppressions,
      the standard addition method was applied. First, the sample was analyzed and then
      the sample involving the addition of calibration standards is analyzed. Although
      this method requires two LC-MS runs per analysis, effective correction of
      quantitative errors was found.

PMID- 11820280
TI  - Analysis of polynitrophenols and hexyl by liquid chromatography-mass spectrometry
      using atmospheric pressure ionisation methods and a volatile ion-pairing reagent.
AB  - An LC-MS method for the determination of picric acid (2,4,6-trinitrophenol), its
      reductive transformation products picramic acid (2-amino-4,6-dinitrophenol) and
      iso-picramic acid (4-amino-2,6-dinitrophenol) and hexyl (2,2',4,4',6,6'
      hexanitrodiphenylamine) has been developed. The analytes were separated using ion
      pairing chromatography with a volatile ion-pairing reagent suitable for
      subsequent MS detection. The performance of an atmospheric pressure chemical
      ionisation (APCI) and an electrospray ionisation (ESI) interface was compared.
      ESI-MS is more sensitive for the analytes, especially for hexyl and picric acid,
      APCI-MS delivered more fragments necessary for unequivocal identification. With
      LC-ESI-MS limits of detection using single ion monitoring (SIM) mode are 4 ng
      (iso-picramic acid), 800 pg (picramic acid), 400 pg (picric acid) and 80 pg
      (hexyl). For quantification, 15N-picric acid was used as an internal standard.
      Using this new method, the degradation of picric acid in soil was monitored in a
      laboratory study. Furthermore, the presence of picramic acid was for the first
      time verified in soil samples from a former ammunition plant.

PMID- 11820281
TI  - Extraction of endoglucanase I (Ce17B) fusion proteins from Trichoderma reesei
      culture filtrate in a poly(ethylene glycol)-phosphate aqueous two-phase system.
AB  - Endoglucanases (EGI) (endo-1,4-beta-D-glucan-4-glucanohydrolase, EC 3.2.1.4,
      Ce17B) of Trichoderma reesei are industrially important enzymes. Thus, there is a
      great need for development of a primary recovery method suitable for large-scale
      utilization. In this study we present a concept applicable for large-scale
      purification of an EGI fusion protein by one-step extraction in a poly(ethylene
      glycol) PEG-sodium/potassium phosphate aqueous two-phase system. EGI is a two
      module enzyme composed of an N-terminal catalytic module and a C-terminal
      cellulose binding module (CBM) separated by a glycosylated linker region.
      Partitioning of six different EGI constructs, containing the C-terminal
      extensions (WP)2, (WP)4 or the amphiphilic protein hydrophobin I (HFB) of T.
      reesei instead of the CBM were studied to evaluate if any of the fusions could
      improve the partition coefficient sufficiently to be suitable for large-scale
      production. All constructs showed improved partitioning in comparison to full
      length EGI. The (WP)4 extensions resulted in 26- to 60-fold improvement of
      partition coefficient. Consequently, a relative minor change in amino acid
      sequence on the two-module protein EGI improved the partition coefficient
      significantly in the PEG 4000-sodium/potassium phosphate system. The addition of
      HFBI to EGI clearly enhanced the partition coefficient (K=1.2) in comparison to
      full-length EGI (K=0.035). Partitioning of the construct with (WP)4 fused to the
      catalytic module and a short sequence of the linker [EGI(core-P5)(WP)4] resulted
      in the highest partition coefficient (K=54) and a yield of 98% in the PEG phase.
      Gel electrophoresis showed that the construct with the (WP)4 tag attached after a
      penta-proline linker could be purified from the other bulk proteins by only a
      single-step separation in the PEG 4000-sodium/potassium phosphate system. This is
      a major improvement in comparison with the previously studied model (ethylene
      oxide-propylene oxide)-dextran system. Hence, this construct will be suitable for
      further optimization of the extraction of the enzyme in a PEG 4000
      sodium/potassium phosphate system from culture filtrate.

PMID- 11820282
TI  - Nd-Fe-B alloy-densified agarose gel for expanded bed adsorption of proteins.
AB  - Novel dense composite adsorbents for expanded bed adsorption of protein have been
      fabricated by coating 4% agarose gel onto Nd-Fe-B alloy powder by a water-in-oil
      emulsification method. Two composite matrices, namely Nd-Fe-B alloy-densified
      agarose (NFBA) gels with different size distributions and densities, NFBA-S (50
      165 microm, 1.88 g/ml) and NFBA-L (140-300 microm, 2.04 g/ml), were produced.
      Lysozyme was used as a model protein to test the adsorption capacity and kinetics
      for the NFBA gels modified by Cibacron blue 3GA (CB-NFBA gels). Liquid-phase
      dispersion behavior in the expanded beds was examined by measurements of
      residence time distributions, and compared with that of Streamline SP (Amersham
      Pharmacia Biotech, Sweden). The dependence of axial mixing in the expanded beds
      on flow velocity, bed expansion degree. settled bed height, and viscosity of
      liquid phase was investigated. Breakthrough curves of lysozyme in the expanded
      beds of the CB-NFBA gels were also examined. The dynamic binding capacity at 5%
      breakthrough was 23.3 mg/ml matrix for the CB-NFBA-S gels, and 16.7 mg/ml matrix
      for the CB-NFBA-L, at a flow velocity of 220 cm/h. The results indicate that the
      NFBA gels are promising for expanded bed adsorption of proteins.

PMID- 11820283
TI  - Impact of the physical and topographical characteristics of adsorbent solid
      phases upon the fluidised bed recovery of plasmid DNA from Escherichia coli
      lysates.
AB  - A comparison is made of the performance of two types of adsorbent solid phases
      (commercially sourced Streamline composites and custom-assembled Zirblast
      pelliculates), derivatised with similar anion exchange chemistries and applied to
      the recovery of plasmid DNA from Escherichia coli extracts prepared by chemical
      lysis and coarse filtration. Streamline and Zirblast adsorbents were
      characterised by average particle diameters of 200 and 95 microm, densities of
      1.16 and 3.85 g/m2, and small ion capacities of 170 and 8 micromol/ml settled
      adsorbent, respectively. Detailed analysis of products and impurities in a full
      operational cycle of adsorption, washing, pre-elution, elution and regeneration
      processes was enabled by the harnessing of a battery of analyses for nucleic acid
      and organic solute content of feedstocks and bed effluents exploiting ultra
      violet spectrophotometry, agarose gel electrophoresis and specific reactions with
      the fluorescent probe PicoGreen. In comparative tests operated under near
      identical conditions, Streamline and Zirblast adsorbents exhibited plasmid
      recoveries of 76 and 90% of bound product characterised by purity ratios
      (relative PicoGreen and A254 estimates of mass) of 9 and 32, respectively.
      Conclusions are drawn regarding the specific impact of the physical and
      topographical characteristics of solid-phase geometry upon product throughput,
      achievable product purity, process time-scales and operational economics for the
      manufacture of plasmid DNA.

PMID- 11820284
TI  - Diastereomeric resolution of nucleoside analogues, new potential antiviral
      agents, using high-performance liquid chromatography on polysaccharide-type
      chiral stationary phases.
AB  - This paper describes the separation of the four sets of stereoisomers of
      nucleoside analogs, new potential antiviral agents by direct analytical HPLC
      methods using derivatized cellulose and amylose chiral stationary phases. The
      resolution was made using normal-phase methodology with a mobile phase consisting
      of n-hexane-alcohol (ethanol or 2-propanol) in various percentages, and a silica
      based cellulose tris-3,5-dimethylphenylcarbamate (Chiralcel OD-H), or tris
      methylbenzoate (Chiralcel OJ) and a silica-based amylose tris-3,5
      dimethylphenylcarbamate (Chiralpak AD) or tris-(S)-1-phenylethylcarbamate
      (Chiralpak AS). The effects of structural features on the extent of
      discrimination between the stereoisomers were examined through the retention, the
      selectivity and the resolution factors as well as the elution order. Baseline
      separation (Rs>1.5) was easily obtained in many cases. The resolution results
      were complementary between the different columns.

PMID- 11820285
TI  - Determination of malondialdehyde in breath condensate by high-performance liquid
      chromatography with fluorescence detection.
AB  - An automated and rapid method for quantifying malondialdehyde (MDA) in breath
      condensate was developed and validated. The method is based on derivatisation
      with thiobarbituric acid, HPLC separation and fluorescence detection and is
      optimised for determination of MDA in breath condensate. Sample collection is non
      invasive and simple. The detection limit (4.1 nM) is low, precision is good and
      the analysis time is short. The response is linear in the concentration range of
      0.020 to 1.0 microM. Samples could be stored for 1 month at -20 degrees C and for
      3 months at -80 degrees C without losses. Using this method, there was no
      statistically significant difference between patients with asthma and patients
      without asthma. However, among females, subjects with asthma had higher MDA
      levels as compared to females without asthma (0.17 vs. 0.12 pmol/s, p=0.04). The
      use of the method when studying airway inflammation has to be further evaluated.

PMID- 11820286
TI  - Rapid and sensitive method for the analysis of carbon monoxide in blood using gas
      chromatography with flame ionisation detection.
AB  - In order to measure changes in physiological CO concentrations in blood with good
      accuracy, a method was developed using gas chromatography with flame ionisation
      detection (250 degrees C). A nickel catalyst system was fitted to convert CO to
      methane at 375 degrees C after separation with a molecular sieve column at 35
      degrees C. Helium was used as carrier at 30 ml/min. Porcine or human blood (400
      microl) was sampled in gastight tubes and treated with sulfuric acid and saponin
      (800 microl). Accuracy was 1.4% and 1.5% (RSD), respectively. Precision was 2.8%
      (porcine blood). Limit of detection was 0.01 nmol/ml gas and limit of
      quantification 12 nmol/ml blood. Calibration was made in the interval 12-514
      nmol/ml blood (corresponding to 0.1-6% COHb). Samples were stable for at least a
      month at +4 degrees C. This paper describes a method with high sensitivity and
      good accuracy, suitable for analysis of low CO concentrations.

PMID- 11820287
TI  - Characterization and inhibition study of MurA enzyme by capillary
      electrophoresis.
AB  - A capillary electrophoresis-based enzyme assay for UDP-N-acetylglucosamine
      enolpyruvyl transferase (MurA) is described. This method, based on UV detection,
      provides baseline separation of one of the reaction products, enolpyruvyluridine
      5'-diphospho-N-acetylglucosamine (EP-UDP-GlcNAc), from substrates
      phosphoenolpyruvate (PEP) and uridine 5'-diphospho-N-acetylglucosamine (UDP
      GlcNAc) within 4 min. The other product, phosphate, is not detectable by UV at
      200 nm. Quantitation of individual components, substrates or product, can be
      accomplished based on the separated peaks. This methodology was used to determine
      the Michaelis constant, Km, and product formation rate constant, Kcat, for MurA.
      Additionally, the CE method was used to evaluate the inhibition effects on MurA
      using one specific compound as an example. By following similar procedures, the
      apparent Km values in the presence of different inhibitor concentrations were
      determined. The inhibition constant, Ki, can be determined from these apparent Km
      values. In addition, this CE method can be used to study the inhibition
      mechanism. The principle of this approach is generally applicable to other enzyme
      studies.

PMID- 11820288
TI  - Purification of anti-MUC1 antibodies by peptide mimotope affinity chromatography
      using peptides derived from a polyvalent phage display library.
AB  - A polyvalent, lytic phage display system (T7Select415-1b) displaying a random
      peptide library has been investigated for its ability to discover novel mimotopes
      reactive with the therapeutic monoclonal antibody C595. Sequence analysis of
      enriched phage lead to the identification of a predominant sequence RNREAPRGKICS,
      and two other consensus sequences RXXP and RXP. The novel synthetic peptide
      RNREAPRGKICS was linked to beaded agarose and the performance as a mimotope
      affinity chromatography matrix evaluated. Antibody purified using the novel
      matrix was found to be of higher specific reactivity than antibody purified using
      the conventional epitope matrix (peptide APDTRPAPG). The RNREAPRGKICS peptide
      binding to C595 demonstrated a higher equilibrium association constant (K(A)=0.75
      x 10(6)) than the epitope peptide (K(A)=0.16 x 10(6)). Circular dichroism showed
      that the novel peptide had a more highly ordered structure at 4 degrees C and
      room temperature, than the epitope peptide.

PMID- 11820289
TI  - Purification of hepatocyte growth factor using polyvinyldiene fluoride-based
      immobilized metal affinity membranes: equilibrium adsorption study.
AB  - Polyvinyldiene fluoride (PVDF)-based affinity membranes with immobilized copper
      ions were developed in this study. The resulting membranes were tested for their
      adsorption properties using a model protein, lysozyme, in batch mode. First,
      different lengths of diamine were utilized as spacer arms to immobilize the metal
      ions onto the membranes. It was found that the application of 1,8-diaminooctane
      as the spacer arm led to the highest adsorption capacity. Moreover, the effects
      of pH and salt concentration were investigated to distinguish the proportion of
      specific and nonspecific interactions. A big fraction of lysozyme adsorption
      capacity for the immobilized metal affinity membranes was considered to come from
      nonspecific electrostatic interactions, which could be reduced by increasing salt
      concentration. Lastly, the purification of hepatocyte growth factor (HGF) from
      insect cell supernatant was performed using the immobilized metal affinity
      membranes in batch mode. HGF was found in the elution condition using EDTA,
      indicating the successful purification of HGF.

PMID- 11820290
TI  - On-line synthesis utilizing immobilized enzyme reactors based upon immobilized
      dopamine beta-hydroxylase.
AB  - Immobilized enzyme reactors (IMERs) based upon dopamine beta-hydroxylase (DBH)
      have been developed. Immobilized artificial membrane (IAM) and glutaraldehyde-P
      (Glut-P) stationary phases have been used to immobilize DBH. When DBH is
      immobilized on the Glut-P interphase the enzyme is outside the stationary phase
      whereas with the IAM interphase the enzyme is embedded within the interphase
      surroundings. The activity of each IMER and their ability for on-line
      hydroxylation has been investigated. The resulting IMERs are enzymatically active
      and reproducible. The IMERs can be utilized through the use of coupled
      chromatography to characterize the cytosolic (DBH-Glut-P-IMER) and membrane-bound
      (DBH-IAM-IMER) forms of the enzyme. The substrate is injected onto the individual
      IMERs and the reactants and products are eluted onto a phenylboronic acid column
      for on-line extraction. The substrates and products are then transported via a
      switching valve to coupled analytical columns. The results demonstrate that
      enzyme-substrate and enzyme-inhibitor interactions can be investigated with the
      on-line system. These IMERs can be utilized for the discovery and
      characterization of new drug candidates specific for the soluble form and
      membrane-bound form of DBH. The effects of flow-rate, contact time, pH and
      temperature have also been investigated.

PMID- 11820292
TI  - High-performance liquid chromatographic determination for aristolochic acid in
      medicinal plants and slimming products.
AB  - A HPLC procedure with a silica gel RP-18 reversed-phase column for the
      determination of aristolochic acids I, II in medicinal plants and slimming
      products was developed. The mobile system 0.3% ammonium carbonate solution
      acetonitrile (75:25, v/v) with pH 7.5 was the optimal buffer to clearly separate
      aristolochic acids I, II within 20 min. The recovery of aristolochic acids I, II
      in medicinal plants and slimming products was better than 90% by extracting with
      methanol and purifying through a PHP-LH-20 column. The major component was
      aristolochic acid I in Aristolochia fangchi and the level ranged from 437 to 668
      ppm. Aristolochic acid II was the major component for Aristolochia contorta and
      its range was <1-115 ppm. Twelve out of 16 samples of slimming pills and powders
      contained aristolochic acids I and/or II. The major component in most slimming
      products was aristolochic acid II and the level ranged from <1 to 148 ppm. It may
      indicate that slimming products were not mainly made of A. fangchi.

PMID- 11820291
TI  - Doping control for methenolone using hair analysis by gas chromatography-tandem
      mass spectrometry.
AB  - A sensitive, specific and reproducible method for the quantitative determination
      of methenolone in human hair has been developed. The sample preparation involved
      a decontamination step of the hair with methylene chloride. The hair sample
      (about 100 mg) was solubilized in 1 ml 1 M NaOH, 15 min at 95 degrees C, in
      presence of 1 ng testosterone-d3 used as internal standard. The homogenate was
      neutralized and extracted using consecutively a solid-phase (Isolute C18 eluted
      with methanol) and a liquid-liquid (pentane) extraction. The residue was
      derivatized by adding 50 microl MSTFA-NH4I-2-mercaptoethanol (1000:2:5, v/v/v),
      then incubated for 20 ml at 60 degrees C. A 1.5-microl aliquot of the derivatized
      extract was injected into the column (HP5-MS capillary column, 5% phenyl-95%
      methylsiloxane, 30 m x 0.25 mm I.D., 0.25 microm film thickness) of a Hewlett
      Packard (Palo Alto, CA, USA) gas chromatograph (6890 Series). Methenolone was
      detected by its parent ion at m/z 446 and daughter ions at m/z 208 and 195
      through a Finnigan TSQ 700 MS-MS system. The assay was capable of detecting 1
      pg/mg of methenolone when approximately 100 mg hair material was processed.
      Linearity was observed for methenolone concentrations ranging from 2 to 100 pg/mg
      with a correlation coefficients of 0.965-0.981. Intra-day and between-day
      precisions at 2, 10 and 25 pg/mg were 10.9-14.1% and 13.7-16.8%, respectively,
      with an extraction recovery of 97.6%. The analysis of a strand of hair obtained
      from two bodybuilders, revealed the presence of methenolone at the concentrations
      of 7.3 and 8.8 pg/mg.

PMID- 11820293
TI  - Therapeutic isoniazid monitoring using a simple high-performance liquid
      chromatographic method with ultraviolet detection.
AB  - Simultaneous measurement of isoniazid and its main acetylated metabolite
      acetylisoniazid in human plasma is realized by high-performance liquid
      chromatography. The technique used is evaluated by a factorial design of
      validation that proved to be convenient for routine drug monitoring. Plasma
      samples are deproteinized by trichloroacetic acid and then the analytes are
      separated on a microBondapak C18 column (Waters). Nicotinamide is used as an
      internal standard. The mobile phase is 0.05 M ammonium acetate buffer (pH 6)
      acetonitrile (99:1, v/v). The detection is by ultraviolet absorbance at 275 nm.
      The validation, using the factorial design allows one to: (a) test the systematic
      factors of bias (linearity and matrix effect); (b) estimate the relative standard
      deviations (RSDs) related to extraction, measure and sessions assay. The
      linearity is confirmed to be within a range of 0.5 to 8 microg/ml of isoniazid
      and 1 to 16 microg/ml of acetylisoniazid. This method shows a good repeatability
      for both extraction and measurement (RSD INH=3.54% and 3.32%; RSD Ac.INH=0.00%
      and 5.97%), as well as a good intermediate precision (RSD INH=7.96%; RSD
      Ac.INH=15.86%). The method is also selective in cases of polytherapy as many
      drugs are associated (rifampicin, ethambutol, pyrazinamide, streptomycin). The
      matrix effect (plasma vs. water) is negligible for INH (3%), but statistically
      significant for Ac.INH (11%). The application of this validation design gave us
      the possibility to set up an easy and suitable method for INH therapeutic
      monitoring.

PMID- 11820294
TI  - Chromatographic characterization of synthetic peptides: SPf66 malaria vaccine.
AB  - The development and validation of a quantitative size-exclusion chromatography
      (SEC) method for SPf66 malaria vaccine was achieved. The results show the
      reliability of the analytical method for the intended use. SPf66 malaria vaccine
      characterization was perforrmed using both relative techniques such as the
      conventional SEC and absolute techniques: mass spectrometry and multi-angle laser
      light scattering detection. The relative and absolute molecular masses were in
      the 4600-18,000 Da range. The results clearly indicate the presence of the
      monomer and dimer species, whereas the third species could be the trimer or
      tetramer.

PMID- 11820295
TI  - Determination of melagatran, a novel, direct thrombin inhibitor, in human plasma
      and urine by liquid chromatography-mass spectrometry.
AB  - Analytical methods for the determination of melagatran (H 319/68) in biological
      samples by liquid chromatography (LC)-positive electrospray ionization mass
      spectrometry using multiple reaction monitoring are described. Melagatran in
      plasma was isolated by solid-phase extraction on octylsilica, either in separate
      extraction tubes or in 96-well plates. Absolute recovery of melagatran from
      plasma was >92%. Melagatran and the internal standard, H 319/68 D2 13C2, were
      separated from other sample components by LC utilizing a C18 stationary phase and
      a mobile phase comprising 35% acetonitrile and 0.08% formic acid in 0.0013 mol/l
      ammonium acetate solution. After dilution, urine was injected directly onto the
      LC column and subjected to gradient LC. The relative standard deviation was 1-5%
      for concentrations above the limit of quantification, which was estimated for
      plasma at 10 or 25 nmol/l for sample volumes of 500 or 200 microl, respectively,
      and 100 nmol/l for urine.

PMID- 11820296
TI  - Determination of tylosin residues in different animal tissues by high performance
      liquid chromatography.
AB  - A HPLC method to determine and quantify tylosin residues from calves, pigs and
      poultry is reported. This procedure permitted tylosin to be separated from
      muscle, liver, kidney and fat after a simple extraction with chloroform or ethyl
      acetate under basic conditions. The analytical methodology showed a high
      specificity and sensitivity and an adequate precision and accuracy with a limit
      of quantification of 50 microg/kg. Eight calves were administered 20 mg/kg/day of
      tylosin for 5 days and slaughtered at 7 and 14 days post-administration. Results
      showed that at the 14th day tylosin levels were lower than the MRL in all target
      tissues.

PMID- 11820297
TI  - Evaluation of the predictive power of calculation procedure for molecular
      hydrophobicity of some estradiol derivates.
AB  - Several calculation procedures for log P values based on the fragmental and
      atomic contributions are compared with experimental reversed-phase liquid
      chromatography (RPLC) retention of estradiol derivates. The RPLC experiments were
      performed on HPTLC and HPLC commercially available stationary phases. Binary
      solvent mixtures of methanol-water and acetonitrile-water were used as mobile
      phases. The correlation between log P and various chromatographically obtained
      hydrophobicity parameters (R(M)0, log k(w) and phi0) are quantified. The R(M)0,
      i.e., log k(w) were obtained by linear extrapolation of retention to 0% organic
      modifier. Phi0 values were obtained from the slopes and intercepts of such linear
      relationship. The mutual relationship between phi(0,MeOH) and phi(0,ACN) values
      of the compounds were discussed. The obtained statistical results can be
      summarized in the following order of reliabilities for different log P
      calculation methods: Broto>ACD/logP>Crippen>Rekker>Viswanadhan.

PMID- 11820298
TI  - Simultaneous determination of citalopram, fluoxetine, paroxetine and their
      metabolites in plasma by temperature-programmed packed capillary liquid
      chromatography with on-column focusing of large injection volumes.
AB  - A miniaturized temperature-programmed packed capillary liquid chromatographic
      method with on-column large volume injection and UV detection for the
      simultaneous determination of the three selective serotonin reuptake inhibitors
      citalopram, fluoxetine, paroxetine and their metabolites in plasma is presented.
      An established reversed-phase C8 solid-phase extraction method was employed, and
      the separation was carried out on a 3.5-microm Kromasil C18 0.32x300 mm column
      with temperature-programming from 35 (3 min) to 100 degrees C (10 min) at 1.3
      degrees C/min. The mobile phase consisted of acetonitrile-45 mM ammonium formate
      (pH 4.00) (25:75, v/v). The non-eluting sample focusing solvent composition
      acetonitrile-45 mM ammonium formate (pH 4.00) (3:97, v/v) allowed injection of 10
      microl or more of the plasma extracts. The method was validated for the
      concentration range 0.05-5.0 microM, and the calibration curves were linear with
      coefficients of correlation >0.993. The limits of quantification for the
      antidepressants and their metabolites ranged from 0.05 to 0.26 microM. The within
      and between assay precision of relative peak height were in the range 2-22 and 2
      15% relative standard deviation, respectively. The within and between assay
      recoveries were in the 61-99 and 54-92% range for the antidepressants,
      respectively, and between 52-102 and 51-102% for the metabolites.

PMID- 11820299
TI  - New approaches for high-yield purification of Mullerian inhibiting substance
      improve its bioactivity.
AB  - We have established a new method to purify Mullerian inhibiting substance (MIS)
      with higher purity and recovery over existing procedures. Recombinant human MIS
      was expressed in Chinese hamster ovary cells and secreted into chemically defined
      serum-free media. The secreted products were concentrated by either precipitation
      with ammonium sulfate or lectin-affinity chromatography, each of which was
      followed by anion-exchange chromatography. Further separation of the active
      carboxy-terminal domain of MIS was achieved after cleavage by plasmin followed by
      lectin-affinity chromatography. This method may be applicable to other members of
      the transforming growth factor beta family with which MIS shares sequence
      homology.

PMID- 11820300
TI  - Determination of topotecan in human whole blood and unwashed erythrocytes by high
      performance liquid chromatography.
AB  - A reversed-phase HPLC method for the quantitative determination of total
      topotecan in human whole blood and unwashed erythrocytes has been developed and
      validated in terms of sensitivity, specificity, precision and accuracy. Linear
      calibration curves were constructed in the range of 0.20 to 50.0 ng/ml. The
      sample pre-treatment for whole blood involved a two-step extraction with methanol
      and perchloric acid. Prior to extraction, erythrocytes were separated from other
      blood components by centrifugation in MESED instruments. Separations were
      achieved on an Inertsil ODS-80A analytical column (150x4.6 mm, 5 microm particle
      size), eluted at 50 degrees C and a flow-rate of 1.00 ml/min, with a mixture of
      100 mM ammonium acetate (pH 6.0)-tetrahydrofuran (94.6:5.4, v/v). Fluorescence
      detection was performed using excitation and emission wavelengths of 381 and 525
      nm, respectively. With the applied method, 80% of topotecan was extracted out of
      whole blood. The lower limit of quantitation in whole blood was established at
      0.20 ng/ml with within-run and between-run precisions, respectively, ranging from
      1.7 to 9.3% and 1.5-6.1%, while the accuracy ranged from 100 to 113%. The
      described method will be used in clinical studies to explore the role of
      erythrocytes in the overall kinetic behavior of topotecan.

PMID- 11820301
TI  - Soft tissue conjunctivo-rhinostomy.
AB  - PURPOSE: To evaluate the results of implantation of a tubular prosthesis between
      the medial palpebral canthus and the nasal fossa, through the soft tissues of the
      face, in cases of irrecuperable damage of the lacrimal canaliculi. MATERIAL AND
      METHODS: Fifty eyes with canalicular destruction were operated, placing a
      silicone and Pyrex tubular prosthesis between the lacrimal caruncle and the nasal
      vestibulum, running almost vertically through the soft tissues of the face,
      without osteal perforation. RESULTS: Lacrimal flow was restored in 47 cases.
      There were three cases of dislocation of the prosthesis, three infections and
      five papillomata. CONCLUSIONS: Vertical conjunctivo-rhinostomy without osteal
      perforation is an easy and efficient solution for irrecuperable occluded
      canaliculi.

PMID- 11820302
TI  - Flap complications in our learning curve of laser in situ keratomileusis using
      the Hansatome microkeratome.
AB  - PURPOSE: To determine the incidence and the type of flap complications in our
      initial series of eyes undergoing laser in situ keratomileusis and the impact of
      microkeratome-related complications on best spectacle-corrected visual acuity.
      METHODS: We reviewed the charts of the 630 consecutive eyes operated in the
      Refractive Surgery Department of Cerrahpasa Medical School, University of
      Istanbul, Turkey using the Hansatome microkeratome and the Summit, SVS Apex Plus
      excimer laser between March 1998 and November 1999. The mean follow-up was 12.6
      months. RESULTS: The incidence of total flap complications was 19.8%. Flap folds
      (5%) were the most common complication. The incidence of epithelial ingrowth was
      3.3%. Diffuse lamellar keratitis was encountered in 20 cases (3.17%). Displaced
      flaps were seen shortly after the procedure in 8 eyes (1.26%) and repositioned
      immediately. Improper keratectomy occurred in 14 eyes (2.2%) and incomplete
      keratectomy in four procedures (0.63%). The presence of interface debris and
      hemorrhage was each 1.9%. We observed one interface abscess, which was culture
      negative and cured with fortified antibiotics, and one free flap. CONCLUSIONS:
      Although the LASIK procedure with the Hansatome had an easy learning curve
      without any of the serious complications that frequently occur in this phase, we
      still observed flap related complications that affected visual outcome.

PMID- 11820303
TI  - The phenotype of arg555trp mutation in a large Turkish family with corneal
      granular dystrophy.
AB  - PURPOSE: A large Turkish family with 52 members, 26 of whom had Groenouw type 1
      corneal granular dystrophy was evaluated by genetic linkage studies and mutation
      analyses. Phenotype-genotype correlations were also assessed. METHODS: DNA from
      peripheral blood lymphocytes of 22 family members was used in establishing
      linkage to chromosome 5q31. Single-strand conformation polymorphism analysis was
      done to detect mutations in exons 4 and 12 of the human transforming growth
      factor beta-induced gene located on chromosome 5q31. Automated sequencing was
      performed on exon 12 of an affected patient. RESULTS: Patients yonger than 15
      years of age had typical linear, granular opacities whereas adults had coarser,
      deeper granular stromal deposits. These changes were not associated with
      recurrent erosions or significant visual disabilities. The family was linked to
      chromosome 5q31 and a DNA shift was observed on exon 12 of affected patients. CGG
      to TGG transition producing R555W mutation was found. CONCLUSIONS: Segregation of
      Arg555Trp has been described as causing Groenouw type I corneal dystrophy of
      variable severity in patients of various ethnic backgrounds. In this large
      Turkish pedigree, the Arg555Trp mutation was associated with a mild phenotype
      that became clinically evident at five years of age but which remained
      asymptomatic in terms of corneal erosions.

PMID- 11820304
TI  - Retinal vessel reaction to short-term IOP elevation in ocular hypertensive and
      glaucoma patients.
AB  - PURPOSE: Regulation of ocular blood flow might be impaired in glaucoma patients.
      We compared the reaction of retinal vessels to a short-term increase of
      intraocular pressure (IOP), using a retinal vessel analyzer (RVA), in normal
      volunteers, ocular hypertensive patients (OH) and primary open angle glaucoma
      patients (POAG). METHODS: Ten healthy subjects (56+/-8 years, IOP 13.7+/-1.6
      mmHg), 10 OH patients (55+/-12 years, IOD 23.4+/-4.1 mmHg) and 11 POAG patients
      (60+/-11 years, IOP 23.3+/-1.95 mmHg) were evaluated. Arterial and venous retinal
      vessel diameter was measured continuously before, during and after raising IOP to
      suprasystolic values by the suction cup method, described as ocular oscillo
      dynamography. RESULTS: The change in vessel diameter after the IOP rise differed
      in its temporal sequence and in absolute values depending on the group examined.
      In the retinal branch veins the reduction of vessel diameter during the IOP rise
      was significantly different in POAG (0%+/-6.7) and volunteers (-6.7%+/-8.5; p =
      0.06) and in POAG and OH (-6.7%+/-7.0; p = 0.04). At 70-130 sec after IOP
      increase a dilatation occurred, again differing significantly in POAG (+5.8%+/
      3.9) and volunteers (+9.7%+/-4.3; p = 0.03). Systemic blood pressure did not show
      any significant differences between groups or during the course of the
      examination. DISCUSSION: At short-term rise in IOP leads to less retinal vessel
      reaction in POAG patients than in volunteers and OH. This might be due to
      impaired autoregulation to ocular perfusion changes in POAG patients.

PMID- 11820305
TI  - Early hyperbaric oxygen therapy for retinal artery occlusion.
AB  - PURPOSE: To assess whether early hyperbaric oxygenation (HBO) treatment has a
      beneficial effect on visual results after retinal artery occlusion (RAO).
      METHODS: A comparative retrospective study in which medical records of all HBO
      treated RAO patients in our department were reviewed and compared with matched
      RAO patients not treated by HBO (from a different medical center). Mean visual
      acuity (VA) at completion of treatment, the presence or absence of improvement in
      VA between admission and discharge, and the mean change in VA between admission
      and discharge were noted. All patients treated by HBO had treatment no later than
      8 hours after the beginning of visual symptoms. RESULTS: Mean VA at discharge was
      0.2981 (6/20) in the treated group and 0.1308 (6/46) in the control group (p <
      0.03). In the treated group, 82.9% had an improvement in VA between admission and
      discharge, compared with 29.7% of the control group (p < 0.00001). Mean
      improvement in VA was 0.1957 in the treated group and 0.0457 in the control group
      (p < 0.01). Differences in outcome measures between treatment and control groups
      were found to reflect the difference between treated and untreated hypertensive
      patients. No difference was found between treated and untreated non-hypertensive
      patients. CONCLUSIONS: Early HBO therapy appears to have a beneficial effect on
      visual outcome in patients with RAO. Further large-scale prospective controlled
      studies are needed to confirm this.

PMID- 11820306
TI  - Retinal vein occlusion and factor V Leiden and prothrombin 20210 G:A mutations.
AB  - PURPOSE: The aim of this study was to establish whether the factor V Leiden
      mutation and the prothrombin 20210 G:A mutation were risk factors for retinal
      vein occlusion. METHODS: Blood samples were obtained from 40 patients with
      retinal vein occlusion and from 50 healthy normal volunteers as controls.
      Polymerase chain reaction assays were done to detect factor V Leiden and
      prothrombin 20210 G:A mutations, and the two groups were compared. RESULTS: Two
      (5%) of 40 patients with retinal vein occlusion and three (6%) of 50 controls
      were heterozygous for factor V Leiden (p=0.84). None of the individuals in either
      group had the prothrombin 20210 G:A mutation. CONCLUSIONS: There was no
      significant association between retinal vein occlusion and the factor V Leiden
      mutation.

PMID- 11820307
TI  - Diode laser transscleral retinopexy in rhegmatogenous retinal detachment surgery.
AB  - PURPOSE: To evaluate the safety and efficacy of transscleral diode laser for
      retinopexy in rhegmatogenous retinal detachment surgery. METHODS: Conventional
      retinal detachment surgery with transscleral diode laser retinopexy was performed
      on 52 eyes of 52 patients (22 female, 30 male), aged from 12 to 74 years (mean 51
      + 4.1). RESULTS: Of the 52 eyes 36 (69%) were reattached in a single operation
      and adequate chorioretinal scars were achieved in 34 of them. Additional
      transpupillary laser photocoagulation was performed in two cases in the
      postoperative period. Retinal re-attachment was achieved with exoplant revision
      and transscleral laser retinopexy in six cases (12%). Ten cases (19%) with severe
      PVR were reattached with vitreoretinal surgery. CONCLUSIONS: Transscleral diode
      laser retinopexy was an effective and safe method, with accurate lesion location,
      concurrent permanent laser marks on the retina, and easy transmission through the
      extraocular muscles and solid buckling elements. Minor complications were
      minimized by gaining experience with the technique.

PMID- 11820308
TI  - Von Willebrand factor in subretinal fluid.
AB  - PURPOSE: To measure the vWF antigen concentration (vWF Ag) in subretinal fluid
      (SRF) and blood plasma. METHODS: Prospective study of 30 patients, aged from 15
      to 78 years (mean 52.7 years), undergoing retinal detachment surgery. Excluded
      were patients with venous or arterial disease or any other factors that could
      affect the parameters evaluated. Subretinal samples were obtained at the time of
      routine drainage during retinal detachment surgery. Venous blood samples were
      taken from the cubital vein into sodium citrate solution (9:1) immediately after
      induction of anesthesia but before surgery. VWF in plasma and in SRF and its
      relation to patients' age, sex, the duration and extent of retinal detachment,
      number of retinal tears, and cryopexy application were evaluated. RESULTS: The
      median level of vWFAg in 30 samples of SRF was 6.3%. The median level of vWF Ag
      in blood plasma was 70.34%. The levels of vWF Ag in SRF were significantly lower
      than in blood plasma (p<0.00001). We found no correlation between the vWF Ag
      concentration in plasma or in SRF and sex, the degree of myopia, the duration and
      extent of retinal detachment, number of retinal tears and the use of cryopexy.
      CONCLUSIONS: Determination of vWF Ag showed that this factor in SRF is unrelated
      to patients', sex, the degree of myopia, the duration and extent of retinal
      detachment, number of retinal tears and use of cryopexy.

PMID- 11820309
TI  - Local anaesthesia for vitreoretinal surgery: an audit of patient and surgical
      experience.
AB  - PURPOSE: Local anaesthesia for vitreoretinal surgery is little used as these
      procedures are deemed to be too long and uncomfortable for patients to tolerate.
      In this unit anterior intraconal local anaesthesia is used for most routine
      surgery. We undertook an audit to ensure that surgical standards and patient
      acceptability were not compromised. METHODS: A prospective observational audit
      was performed. Audit data included: Grade of anaesthetist and surgeon; details of
      anaesthetic and operation; compliance of patient; operating conditions and pain
      scores. Anaesthesia was provided with a combined peribulbar and intraconal
      anaesthetic, using bicarbonate buffered lignocaine and bupivacaine 50:50 mixture.
      RESULTS: 135 (76%) had local anaesthesia alone, 13 (7%) had local anaesthesia
      with sedation and 29 (16%) had general anaesthesia. 96.4% of patients were
      compliant and 98.8% of operating conditions were good or excellent. The mean
      perioperative pain score was 0.1 (range of 0-1), 97% said they would choose local
      anaesthesia again. CONCLUSIONS: LA for vitreoretinal surgery is a useful and
      flexible method of anaesthesia, which has been shown to have excellent patient
      tolerance.

PMID- 11820310
TI  - Lincoff temporary balloon buckle in retinal detachment surgery.
AB  - PURPOSE: To assess the long-term anatomical and functional results of balloon
      buckle surgery for rhegmatogenous retinal detachment. PATIENTS AND METHODS:
      Twenty-five selected detachments with a single break or a group of breaks close
      together were treated with a temporary parabulbar balloon. Adhesion was obtained
      with transconjunctival cryopexy and argon laser photocoagulation. Retinal
      detachment was associated with the following risk factors: myopia (15 eyes),
      aphakia (2 eyes), blunt trauma (1 eye). Twenty-three eyes had a detached macula.
      The balloon was withdrawn after one week. The patients were kept under
      observation for at least six months (mean 44.7 months). RESULTS: Initial retinal
      attachment was achieved in 29 eyes. After the balloon was removed redetachment
      occurred in two eyes; thus, complete attachment was attained in 27 eyes. Causes
      of failure were: undetected break (2 eyes), inadequate buckle (4 eyes),
      proliferative vitreoretinopathy (2 eyes). Conventional scleral buckling and
      subretinal fluid drainage was done in all failed cases. Vitrectomy and silicone
      oil were employed in one patient, and finally retinal attachment was achieved in
      all patients. CONCLUSIONS: Temporary balloon buckling is a simple and curative
      technique for a selected group of patients with retinal detachments.

PMID- 11820311
TI  - Eyelid hypertrichosis associated with latanoprost is reversible.
AB  - A 56-year-old woman with primary open-angle glaucoma in an only eye presented
      with hypertrichosis after using Latanoprost to lower IOP. After trabeculectomy
      with adjunctive Mitomycin C, IOP was well controlled and antiglaucoma medications
      could be discontinued. At eight-month follow-up the abnormal eyelashes had
      disappeared.

PMID- 11820312
TI  - Candida keratitis in a patient with candidiasis of the fingernails.
AB  - PURPOSE: To report a case of Candida keratitis following penetrating keratoplasty
      in a patient with Candidiasis of the fingernails. CASE REPORT: An 80 year-old
      male presented with recurrent Candida keratitis following penetrating
      keratoplasty. Patient was found to have evidence of Candidiasis of the
      fingernails. COMMENT: Candidiasis of the fingernails have led to recurrent fungal
      keratitis following penetrating keratoplasty. Cultures grew Candida albicans.
      Preoperative recognition, prompt and appropriate therapy of foci of infection may
      prevent Candida keratitis following penetrating keratoplasty.

PMID- 11820313
TI  - Propionibacterium acnes endophthalmitis in Ahmed glaucoma valve.
AB  - PURPOSE: To report a case of Propionibacterium acnes endophthalmitis in a patient
      with an Ahmed glaucoma valve. CASE REPORT: A nine-year-old boy with bilateral
      congenital glaucoma, with an Ahmed glaucoma valve implanted in the left eye, had
      recurrent conjunctival dehiscence and endophthalmitis. RESULTS: Vitreous cultures
      demonstrated the presence of Propionibacterium acnes. CONCLUSIONS: This is the
      first reported case of Propionibacterium acnes endophthalmitis in an Ahmed
      glaucoma valve and the second one in a glaucoma drainage device. We strongly
      recommend using a patch graft to prevent and treat tube exposure. Conjunctival
      grafts may be useful to close the conjunctiva when there is marked scarring to
      prevent patch exposure and melting or extrusion.

PMID- 11820314
TI  - Transretinal feeder vessel ligature in von Hippel-Lindau disease.
AB  - PURPOSE: To present a new technique called transretinal feeder vessel ligature
      for the treatment of retinal angiomas. METHODS: Case report of a patient with
      peripheral retinal angiomas previously treated unsuccessfully with
      photocoagulation who responded to this new, alternative surgical treatment.
      RESULTS: The retinal angiomas decreased in size although two new feeder vessels
      appeared and the lesions showed a regression pattern after additional laser
      therapy over the vascular tumors. CONCLUSIONS: A transretinal feeder vessel
      ligature in association with vitrectomy and photocoagulation may be useful for
      some advanced or non-responsive cases of retinal angiomas.

PMID- 11820315
TI  - Current aspects of lactate exchange: lactate/H+ transport in human skeletal
      muscle.
AB  - Skeletal muscle is capable of producing and releasing large amounts of lactate
      and at the same time taking up lactate and using it as a respiratory fuel. The
      release and uptake of lactate both involve transmembrane transport, which is
      mediated mainly by a membrane protein called the monocarboxylate transporter
      (MCT). MCTs mediate membrane transport with an obligatory 1:1 coupling between
      lactate and H+ fluxes, and is therefore of great importance for pH regulation,
      especially during intense muscle activity. The total lactate and H+ transport
      capacity is higher in membranes from oxidative fibers than in membranes from more
      glycolytic fibers. There are two isoforms of MCT present in skeletal muscle, MCT1
      and MCT4. In human muscle samples, there is a positive correlation between the
      proportion of type I fibers and MCT1 density. In contrast, the MCT4 density in
      human muscle is independent of fiber type and displays a large interindividual
      variation. Although the two isoforms have identical transport kinetics (Km), they
      may have different roles in muscle. MCT1 and MCT4 respond differently to a high
      intensity training session, which suggests that these two isoforms are regulated
      differently.

PMID- 11820316
TI  - Effect of local blood circulation and absolute torque on muscle endurance at two
      different knee-joint angles in humans.
AB  - The effects of the local blood circulation and absolute torque on muscle
      endurance at different knee-joint angles were determined. The rate of muscle
      deoxygenation (using near-infrared spectroscopy), and the rate of muscle fatigue
      (using the slope of integrated electromyography, iEMG) were evaluated
      concurrently. Nine healthy subjects performed submaximal (50% maximal voluntary
      contraction. MVC) static knee extension at 50 degrees (extended position, EXT)
      and 90 degrees (flexed position, FLEX) joint angles until the target torque could
      no longer be maintained: that time was measured as the endurance time. They
      exercised with the circulation occluded (OCCL), and without (FREE) to study the
      possible effects of the local circulation. Although MVC torque was independent of
      joint angle [mean (SD) FLEX 250.6 (51.7) Nm and EXT 246.5 (46.6) N x m],
      significantly shorter (P<0.01) endurance time in FLEX [FREE 71.1 (10) s and OCCL
      63.1 (8.8) s] than at EXT [FREE 115.3 (30) s and OCCL 106.7 (29.1) s] were
      obtained in both circulatory conditions. The iEMG-time slope was significantly
      greater in FLEX at the proximal and distal portion (P<0.05) in both circulatory
      conditions. Muscle deoxygenation rate in OCCL was significantly greater (P<0.05)
      at FLEX [20.8 (8.0)%] than EXT [10.9 (4.0)%]. The results would suggest that
      different knee-joint angle affects muscle endurance even if the local circulation
      is controlled. Circulatory disturbance would further reduce muscle endurance in
      EXT, but not in FLEX. Because of the greater muscle internal force in FLEX, local
      blood flow might be already limited even with a free circulation. The greater
      muscle deoxygenation and muscle fatigability would be related to the shorter
      muscle endurance in FLEX.

PMID- 11820317
TI  - Hyperbaric oxygen modulates antioxidant enzyme activity in rat skeletal muscles.
AB  - In skeletal muscle the activity of the enzymatic antioxidants superoxide
      dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) is regulated in
      response to generation of reactive oxygen species (ROS). Increased activity of
      these enzymes is observed after repeated bouts of aerobic exercise, a potent
      stimulus for intracellular ROS production. Hyperbaric oxygen (HBO) inhalation
      also stimulates intracellular ROS production although the effects of HBO on
      skeletal muscle SOD, GPx and CAT activity have not been studied. We tested the
      hypothesis that SOD, GPx and CAT activity is modulated in skeletal muscles in
      response to acute and repeated HBO administration. In adult male rats acute HBO
      inhalation (60 mm at 3 atmospheres absolute) reduced catalase activity by
      approximately 51% in slow-twitch soleus muscles. Additionally, repeated HBO
      inhalation (twice daily for 28 days) increased Mn2+-superoxide dismutase activity
      by approximately 241% in fast-twitch extensor digitorum longus muscles. We
      conclude that both acute and repeated HBO inhalation can alter enzymatic
      antioxidant activity in skeletal muscles.

PMID- 11820318
TI  - Electromyogram power spectrum and features of the superimposed maximal M-wave
      during voluntary isometric actions in humans at different activation levels.
AB  - The frequency characteristics of the electromyogram (EMG) power spectrum, such as
      the median or the mean power frequency, as well as the duration of the muscle
      compound action potential response to a single supramaximal electrical stimulus
      (maximal M-wave) may both be related to the conduction velocity (CV) of the
      muscle fibre. To investigate this further, we studied in ten male subjects: the
      EMG of the vastus lateralis, vastus medialis and rectus femoris muscles during
      maximal isometric knee extensions at 40%, 60%, 80% and 100% of maximal voluntary
      contraction and also the maximal M-wave, elicited by a single supramaximal
      stimulus to the femoral nerve, of the same muscles at rest or superimposed on the
      same levels of voluntary contraction. The EMG was recorded during the constant
      force phase of the voluntary contractions, the duration of which was 2.5-4 s,
      with a 1.5 min pause between contractions. The average EMG (aEMG) and the median
      frequency (MF) were then calculated. The results indicated that as aEMG increased
      with increase in force, MF remained unchanged. However, while the amplitude of
      the M-wave was not affected, the duration of the M-wave was shorter as the force
      level increased. The duration of the M-wave may be affected by recruitment of
      faster motor units, by increased firing rate of the active units and by changes
      in the muscle fibre length. The shorter duration of the M-wave observed at higher
      force levels was not, however, accompanied by a corresponding increase in MF. The
      MF could not therefore be used as a parameter to reflect the changes in voluntary
      muscle activation and CV. When MF was calculated by overlapping the fast Fourier
      transform (FFT) windows (0.4 s long window moved data point by data point to the
      right) for 1 s periods of the isometric plateau phase at each force level, the
      difference between the lowest and the highest MF was quite substantial. These
      variations suggest that FFT window placement, i.e. which part of the signal is
      chosen for the analyses, may play an important role even in isometric situations.

PMID- 11820319
TI  - Exercise lactate levels: simulation and reality of aerobic and anaerobic
      metabolism.

PMID- 11820320
TI  - Effects of laboratory versus field exercise on leukocyte subsets and cell
      adhesion molecule expression in children.
AB  - In adults, exercise is a powerful and natural stimulator of immune cells and
      adhesion molecules. Far less is known about these exercise responses during
      childhood and whether or not exercise in real-life activities of healthy children
      might influence immune responses. We compared laboratory exercise (10 x 2 min
      periods of heavy, constant intensity, cycle ergcometer exercise with 1 min rests
      between exercise in nine subjects, aged 9-15 years) with field exercise (90 min
      soccer practice in nine different subjects, aged 9-11 years). Blood was sampled
      before both protocols, 5 min after the 30 min laboratory protocol, and 10-15 min
      after the 90 min field protocol. Both field and laboratory exercise protocols led
      to significant (P<0.05) increases in granulocytes, monocytes, and all lymphocyte
      subpopulations. The mean (SEM) increases were similar for the two protocols
      except for the significantly greater increase in laboratory compared with field
      protocols for natural killer cells [142 (39)% vs 12 (16)%, P<0.001] and monocytes
      [64 (22)% vs 32 (19)%, P<0.001] Both protocols significantly influenced adhesion
      molecules (such as CD54) which have not been previously studied in children.
      However, the adhesion molecule CD8+ CD62L increased to a significantly (P <
      0.001) greater extent in the laboratory [101 (25)%] versus field [34 (25)%]
      protocol. Finally, the density of CD632L on lymphocytes significantly decreased
      with laboratory exercise but showed no change in the field protocol [-20 (3)% vs 
      3 (3)%, P<0.001]. The rapid and substantial immune response in both laboratory
      and field protocols suggests that exercise stimulation of the immune system
      occurs commonly in the real lives of children and may play a role in their
      overall immune status.

PMID- 11820321
TI  - Surface EMG shows distinct populations of muscle activity when measured during
      sustained sub-maximal exercise.
AB  - Muscle activity patterns were measured from the rectus femoris, biceps femoris,
      tibialis anterior and gastrocnemius medialis muscles using electromyography
      (EMG). Recordings were made from six runners while they ran for 30 mm around a
      track at a constant, self-selected pace. They were made from three sites along
      each muscle belly, and for ten consecutive steps on each 450 m lap completed. The
      intensity of the myoelectric signals was resolved into components in time and
      frequency space using wavelet analysis. Distinct populations of high- (170-220
      Hz) and low-frequency (40-60 Hz) components could be seen in the frequency
      spectra. There was no significant effect of the electrode position on the rates
      of change of EMG intensity for any of the muscles, and there was no significant
      difference in these rates between a 150-ms window at the end of the swing phase
      and a 150-ms window during the stride phase of running. There were significant
      differences in the way in which each subject responded to the task, and the way
      in which the FMG intensities changed at the different frequency bands. There was
      a significant reduction in EMG intensity at low frequencies and a significant
      increase at high frequencies, and these changes were ubiquitous for all four
      muscles tested. The frequencies that showed the greatest changes coincided with
      the frequencies where distinct populations of activity occurred within the
      signal. These changes in muscle activity are different from those seen for
      maximal fatiguing contractions. However, they suggest that the patterns of muscle
      recruitment may change during sustained sub-maximal exercise.

PMID- 11820322
TI  - Cyclic mechanical stretching modulates secretion pattern of growth factors in
      human tendon fibroblasts.
AB  - The objective of the study was to investigate whether the response profile of the
      growth factor of human tendon fibroblasts could be beneficially influenced
      through the application of mechanical stretch. It was considered that this would
      elucidate structural and functional problems, often seen after tendon and
      ligament healing. The secretion pattern of transforming growth factor-beta (TGF
      beta), platelet-derived growth factor (PDGF) and basic fibroblast growth factor
      (bFGF) was determined in mechanically stretched fibroblasts and compared to non
      stretched controls. Human tendon fibroblasts were experimentally stretched for 15
      and 60 mm at a frequency of 1 Hz and an amplitude of 5%. The secretion of TGF
      beta PDGF and bFGF was measured by enzyme-linked immuno-sorbent assay. All the
      growth factors investigated were indeed secreted by human tendon fibroblasts both
      in stretched cells and controls. Mechanical stretch increased the secretion
      pattern of the growth factors. The increased concentrations of TGF-beta bFGF and
      PDGF after cyclical mechanical stretching may have a positive influence on tendon
      and ligament healing through stimulation of cell proliferation, differentiation
      and matrix formation.

PMID- 11820323
TI  - Isometric axial rotation of the trunk in the neutral posture.
AB  - The purpose of this study was to measure the torque, the magnitude of the
      electromyogram (EMG) signal and the phase relationship of 14 muscles during trunk
      axial rotation. Fifty normal healthy volunteers (27 males and 23 females) with no
      lower-back injury participated in the study. The subjects were seated in an
      upright position in the axial rotation tester (AROT) after applying surface
      electrodes bilaterally to the following muscles: pectoralis major, rectus
      abdominis, external oblique, internal oblique, latissimus dorsi, and erector
      spinae at T10 and L3. They were stabilized from the hip down, and the shoulder
      harness of the AROT was applied to their shoulders. These subjects performed
      maximal isometric axial rotations to the left and right in a random order. The
      torque and 14 channels of EMG were monitored, and their magnitude, slope of the
      increase in magnitude, and timing of the anticipation and onset activity were
      determined. The results revealed that the females produced 65% of the torque of
      their male counterparts. The pattern and magnitude of EMG in performing these
      tasks were significantly different between males and females (P<0.01). Males
      generated the greatest activity in their ipsilateral latissimus dorsi followed by
      their contralateral external oblique muscles. In the females, maximal EMG
      activity was observed in their contralateral pectoralis muscle. Thus, under the
      current experimental conditions, the females employed a different muscle
      recruitment strategy compared to the males. Each muscle involved in axial
      rotation was significantly different from the other (P < 0.01). The timing
      pattern for these activities was inconsistent, implying that there is no fixed
      order phasic recruitment of the torso muscles during maximal isometric axial
      rotation.

PMID- 11820324
TI  - The expression of lactate transporters (MCT1 and MCT4) in heart and muscle.
AB  - It is now known that lactate traverses the plasma membrane of many tissues,
      including heart and muscle, via a stereo-specific, pH-dependent monocarboxylate
      transport (MCT) system. In the past few years a family of MCTs (MCT1-MCT7) has
      been cloned. Transcripts of MCT1 and MCT4 are detectable in rat and human
      skeletal muscle and in the heart. However, only skeletal muscle expresses both
      the MCT1 and MCT4 proteins, whereas rat heart expresses the MCTI, but not the
      MCT4 protein. The kinetic activities of MCT1(Km=3.5 mM) and MCT4 (Km= 17-34 mM)
      are quite different. Among rat muscles, MCT1 expression is highly correlated with
      the oxidative fiber composition of the muscle, and other indices of oxidative
      metabolism. Lactate uptake from the circulation is also highly correlated with
      the MCT1 content of muscles. MCT4 is confined to fast-twitch (fast glycolytic and
      fast oxidative glycolytic) muscle fibers, in which MCT4 content is correlated
      with indices of anaerobic metabolism. Collectively, these data suggest that MCT1
      and MCT4 are primarily responsible for lactate uptake from the circulation and
      lactate extrusion out of muscle, respectively. Exercise training can increase the
      expression of both MCT1 and MCT4 in human muscle, although the extent of this up
      regulation may be related to the intensity of training. In the rat heart, MCT1
      expression is induced more easily by exercise training than in rat skeletai
      muscle. It appears that MCT1 and MCT4 expression are regulated in a tissue
      specific and isoform-specific manner. Therefore, skeletal muscle lactate
      concentrations are not only regulated by the rate of glycolysis, but also by the
      efficiency of trans-sarcolemmal lactate transport, a process that is regulated by
      the quantity of available MCT proteins.

PMID- 11820325
TI  - Running economy of elite surf iron men and male runners, on soft dry beach sand
      and grass.
AB  - The primary aim of this study was to measure the energetics of six elite surf
      iron men (who participate in regular sand running training), performing steady
      state running trials on grass in shoes at 8, 11 and 14 km x h(-1), and on sand
      bare foot and in shoes, at both 8 and 11 km x h(-1). The net total energy cost
      (EC, J x kg(-1) x m(-1)) was determined from the net steady-state oxygen
      consumption and respiratory exchange ratio (net aerobic EC) plus net lactate
      accumulation (net anaerobic EC). For the sand barefoot and sand in shoes running
      trials at 8 and 11 km x h(-1), net aerobic EC and total net EC (but not anaerobic
      EC) were significantly greater (P < 0.001) than the grass running trial values.
      No differences (P > 0.05) existed between the sand barefoot and sand in shoes
      trials. These measures were compared with data obtained from eight well-trained
      male recreational runners who performed the same protocol in a previous study,
      but who were not accustomed to running on sand. Comparisons of net aerobic EC
      between the two groups for the surface conditions were not significantly
      different (P > 0.05). For net anaerobic EC, the iron man values were
      significantly less (P < 0.02) than the recreational runner values. For net total
      EC, the iron man values were less than the recreational runner values, but the
      differences were only significant when both groups ran on sand barefoot (P <
      0.03: on grass P = 0.158; on sand in shoes P = 0.103). The lower lactate
      accumulation values recorded for the iron men on both grass and sand may indicate
      that running on sand potentially reduces metabolic fatigue when running on firm
      or soft surfaces.

PMID- 11820326
TI  - Influence of ambient temperature on plasma ammonia and lactate accumulation
      during prolonged submaximal and self-paced running.
AB  - This study examined the effects of heat stress on the accumulation of plasma
      ammonia, lactate, and urate during prolonged running. Nine highly trained
      endurance runners completed two running trials in a counterbalanced fashion in
      cool (15 degrees C) and in hot (35 degrees C) humid (60% relative humidity)
      conditions. Subjects ran on a motorised treadmill at 70% of peak treadmill
      running speed for 30 min (submaximal) followed by a self-paced 8-km performance
      run. Blood was drawn at pre-exercise, end-submaximal and end-performance run and
      analysed for plasma ammonia, lactate, and urate. Four subjects failed to complete
      the performance run in the heat and the performance times for the rest of the
      subjects was increased from 27.3 (0.6) min in cool conditions to 31.3 (1.2) min
      in hot conditions (P < 0.05). The end-performance rectal temperature was 38.6
      (0.1) and 39.2 (0.1) degrees C (P<0.05) in cool and hot conditions, respectively.
      Differences in plasma lactate at the end of submaximal running were not
      significant. However, at the end of performance runs lactate was 6.0 (0.9) m mol
      x l(-1) in cool and 3.1 (0.5) mmol x l(-1) in hot conditions, values that were
      significantly different (P<0.05). Plasma ammonia increased from pre-exercise to
      approximately equal to 59 micromol x l(-1) at the end-submaximal runs for both
      coditions and further at the end of performance runs to 108.5 (11) micromol x l(
      1) (P<0.05) in hot but not in cool conditions. Plasma urate increased from pre
      exercise to 311.2 (25.9) micromol x l(-1) at end-submaximal runs and to
      approximately equal to 320.4 micromol x l(-1) at end-performance runs in hot and
      cool environments. The findings that plasma urate accumulation was similar at the
      completion of running in both conditions, while ammonia was significantly
      augmented in hot conditions compared with cool, suggest that ammonia accumulation
      during heat stress exercise might be derived from sources other than purine
      catabolism.

PMID- 11820327
TI  - The effects of replacing a portion of endurance training by explosive strength
      training on performance in trained cyclists.
AB  - To investigate the effects of replacing a portion of endurance training by
      strength training on exercise performance, 14 competitive cyclists were divided
      into an experimental (E; n = 6) and a control (C; n = 8) group. Both groups
      received a training program of 9 weeks. The total training volume for both groups
      was the same [E: 8.8 (1.1) h/week; C: 8.9 (1.7) h/week], but 37% of training for
      E consisted of explosive-type strength training, whilst C received endurance
      training only. Simulated time trial performance (TT), short-term performance
      (STP), maximal workload (Wmax) and gross (GE) and delta efficiency (DE) were
      measured before, after 4 weeks and at the end of the training program (9 weeks).
      No significant group-by-training effects for the markers of endurance performance
      (TT and Wmax) were found after 9 weeks, although after 4 weeks, these markers had
      only increased (P < 0.05) in E. STP decreased (P < 0.05) in C, whereas no changes
      were observed in E. For DE, a significant group-by-training interaction (P <
      0.05) was found, and for GE the group-by-training interaction was not
      significant. It is concluded that replacing a portion of endurance training by
      explosive strength training prevents a decrease in STP without compromising gains
      in endurance performance of trained cyclists.

PMID- 11820328
TI  - Leptin and steroid hormone responses to exercise in adolescent female runners
      over a 7-week season.
AB  - The purpose of the study was to investigate the responses of leptin and steroid
      hormones to maximal exercise in adolescent female runners over a competitive
      season. Seven adolescent female distance runners completed three testing trials
      during weeks 1.4 and 7 of their high-school track season. Blood samples were
      collected before and after a discontinuous graded exercise test to exhaustion
      (GXT) for each trial. Tests were administered during the subjects' normal
      training time (3:30 p.m.-5:00 p.m.). Compared to week 1, peak O2 uptake rose
      significantly during the season and was 10% and 7% higher at weeks 4 and 7,
      respectively. Levels of dehydroepiandrosterone (DHEA), dehydroepiandrosterone
      sulfate (DHEAS), cortisol, testosterone, and leptin increased significantly in
      response to the graded exercise tests. Testosterone levels were also changed over
      the course of the study. Resting testosterone levels and testosterone responses
      to exercise in weeks 4 and 7 were both higher than in week 1. Resting
      concentrations and acute increases of the other hormones were not changed over
      the season. It appears, therefore, that DHEA, DHEAS, cortisol, testosterone and
      leptin concentrations increase in response to running in adolescent female
      runners. Data also suggest that training and/or maturation increases resting
      testosterone concentrations and testosterone responses to running in adolescent
      female runners during a training season.

PMID- 11820329
TI  - Beta-endorphin immunoreactivity during high-intensity exercise with and without
      opiate blockade.
AB  - Nine highly fit men [mean (SE) maximum oxygen uptake, VO2max: 63.9 (1.7) ml x kg(
      1) x min(-1); age 27.6 (1.6) years] were studied during two treadmill exercise
      trials to determine plasma beta-endorphin immunoreactivity during intense
      exercise (80% VO2max). A double-blind experimental design was used, and subjects
      performed the two exercise trials in counterbalanced order. Exercise trials were
      30 min in duration and were conducted 7 days apart. One exercise trial was
      undertaken following administration of naloxone (1.2 3 cm3) and the other after
      receiving a placebo (0.9% NaCl saline; 3 cm3). Prior to each experimental trial,
      a flexible catheter was placed into an antecubital vein and baseline blood
      samples were collected. Thereafter, each subject received either a naloxone or
      placebo bolus injection. Blood samples were also collected after 10, 20 and 30
      min of continuous exercise. beta-Endorphin was higher (P < 0.05) during exercise
      when compared to pre-exercise in both trials. However, no statistically
      significant difference was found (P> 0.05) between exercise time points within
      either experimental trial. beta-endorphin immunoreactivity was greater (P < 0.05)
      in the naloxone than in the placebo trial during each exercise sampling time
      point [10 min: 63.7 (3.9) pg x ml(-1) vs 78.7 (3.8) pg x ml(-1); 20 min: 68.7
      (4.1) pg x ml(-1) vs (4.3) pg x ml(-1); 30 min: 71.0 (4.3) pg x ml(-1) vs
      82.5(3.2) pg x ml(-1)]. These data suggest that intense exer induces significant
      increases in beta-endorphin that are maintained over time during steady-rate
      exercise. Exercise and naloxone had an interactive effect on beta-endorphin
      release that warrants further investigation.

PMID- 11820330
TI  - Ventilatory responses to hypercapnia in divers and non-divers: effects of posture
      and immersion.
AB  - The aim of this study was to determine the effects on respiratory drive of two
      factors, one mechanical (lung volume) and one chemical (sensitivity to
      hypercapnia), that are involved in determining the breath-hold duration (BHD).
      Functional residual capacity was measured by helium dilution with the subject
      seated in air, seated in water and in the prone position in water. Hyperoxic
      hypercapnia rebreathing (Read's method) was carried out under identical
      environmental conditions to assess the effects of CO2 pressure on respiratory
      centre output by measuring ventilation, mean inspiratory flow and occlusion
      pressure. Sixteen healthy volunteers were tested. 8 trained divers and 8 non
      divers. Functional residual capacity decreased for the postures seated in water
      (30.8%-34.8%) and for prone position in water (20.3%-20.9%) when compared to the
      posture seated in air (P<0.0001), all subjects pooled. No difference was found
      between groups. The slopes of the linear regression, which characterised the
      sensitivity to CO2 and were determined with the rebreathing tests, revealed
      differences between the two populations (ventilation: P < 0.0001; mean
      inspiratory flow: P < 0.05). No difference was found for occlusion pressure or
      between the different postures. These results confirmed a lower sensitivity to
      CO2 for trained divers. This adaptation was shown to decrease respiratory centre
      activity at the origin of the breath-hold breaking point. The immersion, did not
      influence respiratory drive, despite a decrease in lung volumes. The authors
      suggest that these findings may be explained by a specific apnoea training and a
      pronounced bradycardia in immersion.

PMID- 11820331
TI  - Mechanism-based therapy for leukemia: a lesson from ATRA therapy.
AB  - In the past two decades, there has been a tremendous increase in our
      understanding of the molecular mechanism of human leukemias. Leukemias are now
      recognized as a deregulated state of cell proliferation, differentiation and
      apoptosis, which is induced by gene alterations, including chromosomal
      translocations. Many of the mechanisms are potentially exploited as new targets
      for drug development. All-trans retinoic acid therapy for acute promyelocytic
      leukemia, which was initially developed as a differentiation therapy in an
      experienced-based manner, is currently known to be the first successful
      oncoprotein-directed therapy. Basic and clinical research into ATRA-resistance
      provides new directions for acute myeloid leukemia therapy. Anti-leukemia therapy
      will continue to lead the field of chemotherapy in the coming decades.

PMID- 11820332
TI  - Squamous cell carcinoma of the vulva and adjacent lesions treated at Nagoya
      University Hospital from 1965 to 1997.
AB  - Japan has a lower incidence of vulvar squamous cell carcinoma (VSCC) than Western
      nations. To pin-point the reasons for this, we reviewed biopsy samples from all
      cases treated at Nagoya University Hospital over the past 33 years in order to
      investigate the background lesions for VSCC. Two of 36 VSCC patients had adjacent
      or coexisting lichen sclerosus (LS), 5 had squamous cell hyperplasia (SCH), and
      16 had vulvar intraepithelial neoplasia (VIN). There were 8 cases in which these
      lesions were thought to be the origin of the VSCC, 1 in which keratinizing
      squamous cell carcinoma (KSC) was seen in LS, 1 in which verrucous SCH was the
      origin, and 6 in which 4 basaloid carcinoma and 2 warty carcinoma developed from
      basaloid VIN and warty VIN, respectively. Although 8 other cases of keratinizing
      or non-keratinizing squamous cell carcinomas (NSC) coexisted with VIN NOS (not
      otherwise specified), differentiated VIN or basaloid VIN, we could not be
      histologically certain of the origin. Among 22 VSCC patients tested for HPV DNA,
      only an 84-year-old woman presenting a histological feature of KSC tested
      positive by in situ hybridization (ISH). It was considered that LS and SCH had
      little and VIN considerable capacity to cause the malignancy of VSCC. We surmise
      that in Japan the majority of squamous cell carcinoma is unrelated to HPV. One
      reason for the low incidence of VSCC is largely due to race; the homogeneous,
      monoethnic Japanese population, as well as the few cases of HPV-related VSCC.

PMID- 11820333
TI  - Diagnosis of ulnar wrist pain.
AB  - In the diagnosis of ulnar wrist pain, physical examinations including provacative
      tests are primary elements in identifying the site and nature of ulnar wrist
      pain. Imagings techniques are helpful for diagnosing occult fractures and distal
      radioulnar subluxation, but unsatisfactory for diagnosing ulnocarpal impaction
      syndrome, tears of the triangular fibrocartilage complex and lunotriquetral
      ligament, and joint mouse, imagings. Therefore, prior to surgical intervention
      arthroscopy is recommended for patients with persistent ulnar wrist pain that
      interferes with their daily activity.

PMID- 11820334
TI  - Retrograde cerebral perfusion with hypothermic circulatory arrest in aortic arch
      surgery: operative and long-term results.
AB  - METHODS: Clinical data were retrospectively collected for 207 consecutive
      patients who underwent aortic arch surgery using continuous retrograde cerebral
      perfusion (CRCP) and hypothermic circulatory arrest (HCA) at Tenri Hospital (138
      patients) from 1988 to 1999, and at Nagoya University Hospital (69 patients) from
      1990 to 2000. One hundred and 3 patients (50%) were operated upon for aortic
      dissection, and 104 patients (50%) for atherosclerotic aneurysm. RESULTS:
      Hospital mortality was 12% (25 patients). HCA times were 44+/-20 minutes.
      Cardiopulmonary bypass time longer than 6 hours, low cardiac output syndrome,
      respiratory failure, and central nervous system (CNS) dysfunction contributed to
      hospital deaths. Late mortality was 16% (34 patients). The predictors of late
      deaths were age (>70 years), total arch replacement, HCA time >60 min., non
      dissecting aneurysm, and postoperative CNS injury. CONCLUSIONS: Operative results
      of aortic arch surgery using CRCP was generally satisfactory. However, the long
      term results of total arch replacement for patients older than 70 years, non
      dissecting aneurysm (particularly ruptured), and postoperative CNS injury were
      poor. Although prolonged duration of HCA may contribute to these poor results,
      other factors such as emergent surgery, late death due to aging, and systemic
      atherosclerosis are also considered to be risk factors.

PMID- 11820335
TI  - Clinical nursing practice.

PMID- 11820336
TI  - Administration of blood transfusions to adults in general hospital settings: a
      review of the literature.
AB  - The Serious Hazards of Transfusion (SHOT) haemovigilance scheme for the United
      Kingdom and Republic of Ireland has clearly indicated that there are avoidable
      risks to which recipients of blood transfusion are exposed. Sometimes errors in
      practice have led to serious and even fatal consequences, particularly when a
      haemolytic response occurs due to an incompatible transfusion. Despite the risks,
      blood transfusion is an important and frequently life-saving therapy and its use
      in clinical practice is common. This paper discusses recently published national
      guidelines for the care of recipients of blood transfusion in the light of a
      review of the literature relevant to the administration of blood transfusions to
      adults in general hospital settings. Recommendations for practitioners, managers
      and teachers are offered in relation to preventing errors and to patient care
      associated with blood transfusion in the context of contemporary emphasis upon
      evidence based care.

PMID- 11820337
TI  - The cycle of homelessness in the lives of young mothers: the diagnostic phase of
      an action research project.
AB  - This paper presents the findings of the first stage of an action research project
      designed to explore the experience of repeated homelessness in the lives of young
      women. An action research strategy was selected because it offered a framework
      within which to work with and for rather than on this vulnerable group of service
      users. The women participating in the research developed a conceptual model that
      captured the essence of their experience, which they named 'Our Cycle'. They also
      proposed a system for service delivery, 'From trauma to recovery: a non
      professional model'. The diagnostic phase of the action research has thus
      resulted in a sound theoretical and practical framework to guide the
      implementation and evaluation stages of the project, currently being funded
      through the United Kingdom Department of Health's Health Action Zone initiative.

PMID- 11820338
TI  - Patients' and practice nurses' perceptions of secondary preventive care for
      established ischaemic heart disease: a qualitative study.
AB  - A significant proportion of patients with established ischaemic heart disease
      remain unrecognized in general practice and those who are receiving treatment are
      experiencing sub-optimal care. The provision of coronary prevention by practice
      nurses may be an important strategy to improve the quality of this care, and this
      is feasible and effective. This study explored what occurred during patients'
      initial assessment for secondary prevention of ischaemic heart disease with a
      practice nurse and investigated patients' and practice nurses' views ofnurse-led
      clinics in primary care. Nurses were effective in history taking and offering
      reassurance and dietary advice, yet were less confident in discussing patients'
      understandings of heart disease and related medication. Practice nurse-led
      coronary preventive care is acceptable to both nurses and patients. Further
      practice nurse education is required in heart disease, cardiac medications and
      skills necessary for exploring and challenging patients' understandings of these
      issues.

PMID- 11820339
TI  - Blood pressure measurement--an observational study of 21 public health nurses.
AB  - The purpose of this study was to observe how public health nurses perform blood
      pressure measurement. Structured observations were made of 21 randomly selected
      public health nurses while they performed three blood pressure measurements. The
      public health nurses used an overall correct method for blood pressure
      measurement. Five nurses out of 21 used the Tri-cuff but the soft cuff was most
      frequently used. When choosing the breadth of the cuff, 10 nurses decided by eye
      and not by the marks on the cuff. To ensure a completely correct method
      additional information is needed by nurses.

PMID- 11820340
TI  - An examination of senior nursing roles: challenges for the NHS.
AB  - Wellhouse NHS Trust moved its inpatient services to the new Barnet General
      Hospital in 1997 and merged with Chase Farm Hospital NHS Trust in 1999. To assist
      with the trust's management of resulting changes in care provision, a short
      project was conducted to examine the nursing services provided by ward managers
      (20) and senior nurses (27), that is nurses who undertake specialist/ advanced
      nursing practice. The project also aimed to present the views of the stakeholders
      (66) with regard to nursing in the trust and nurse-led services. The project
      involved two stages of data collection--focus groups and postal questionnaires.
      The project provided a great deal of information about the nursing service within
      the trust: a profile of the senior nurses, roles and responsibilities, skills and
      competencies, training and development, and support needs for their roles. The
      findings considered a number of issues: (i) employment--diversity of grading for
      posts; (ii) work roles--conflicts in role composition; (iii) stakeholders-
      perspectives of stakeholders on nursing. It is anticipated that the findings are
      not unique to the one trust and that they will contribute to the development of
      new clinical career pathways for senior nurses within the trust.

PMID- 11820341
TI  - Reflective practice and clinical outcomes: practitioners' views on how reflective
      practice has influenced their clinical practice.
AB  - There has been a recent increasing interest in reflective practice in nursing.
      There is a wealth of literature about its apparent advantages and benefits, but
      very little empirical research into clinical outcomes consequent to reflective
      practice. This study attempts an initial exploration into this area. A
      retrospective, three-phase, multi-method study in a single department of nursing
      was conducted. The research sample comprised students and former students of the
      department who had previously participated in an assessed reflective practice
      course or module. Years of experience, speciality or academic level did not have
      a significant influence, but the effectiveness of the facilitator was an
      important factor. The results suggest that reflective practice is regarded highly
      and that most respondents could identify significant, long-term changes to
      clinical practice resulting from it.

PMID- 11820342
TI  - The development of nurse-led clinics in cancer care.
AB  - This paper provides a review of current literature which focuses on issues
      relating to the care of cancer patients in the 21st century and the evolving role
      of the advanced practitioner in nurse-led clinics in cancer care. The review, in
      particular, identifies more specifically the skills used and the patient needs
      which can be met by innovative nurses working in nurse-led clinics. An in-depth
      discussion of a specific nurse practitioner's experience allows some of the
      skills of advanced nursing practice to appear more visible, for example, the
      assessment and investigation of patients experiencing symptoms associated with
      colorectal cancer. The implications for clinicians and educationalists in cancer
      care is highlighted within the conclusions.

PMID- 11820343
TI  - The effect of a clinical nurse specialist in gynaecological oncology on quality
      of life and sexuality.
AB  - Gynaecological malignancy has an immense impact on the well-being of women. For
      many women, however, treatment such as surgery is curative and healthcare
      intervention focuses on the physiological status of the women. The psychological,
      social and sexual consequences of the malignancy and its treatment have received
      little attention in research or in practice. The present study used a mixed
      quantitative and qualitative design to analyse a specialist nurse intervention
      (including psychosexual intervention), and to explain the impact of the illness
      on women's lives. The qualitative arm of the study collected interview data from
      20 women and six partners. The randomized controlled trial sample consisted of 36
      women, with data collected using a quality of life measure (the EORTC QLQ-C30)
      and the Lasry Sexual Functioning scale. This paper focuses on the randomized
      controlled trial data, which identified that sexual functioning and quality of
      life were improved in the active group who received specialist psychosexual
      counselling. However, the validity of the sexual functioning scale is challenged
      by the qualitative results of the study, which emphasize the social meaning of
      sexuality.

PMID- 11820344
TI  - Family involvement in perioperative nursing of adult patients undergoing
      emergency surgery.
AB  - The purpose of this study was to describe how adult patients undergoing emergency
      surgery experience family centredness in perioperative nursing practice. The
      central aim was to generate knowledge to be used while developing the practice,
      education and management of perioperative nursing. Data were collected using a
      questionnaire with emergency surgical patients in five regional hospitals in
      Southern Finland. The number of distributed questionnaires was 132. The response
      rate was 85% (n = 112). The results were mainly described as frequencies and
      percentages. The open-ended sections of the answers were analysed using
      qualitative content analysis. The findings from the open-ended questions were
      used for deepening and complementing the quantitative description of the results.
      In the preoperative phase, ascertaining the family situation and informing the
      family member chosen by the patient were not achieved systematically. Family
      situation was also rarely examined in the intraoperative and postoperative
      phases, although it is central to coping after surgery, especially in home care.
      The results support the view of earlier research about the importance of
      individuality of patients and their families during the perioperative care
      process and hence enhance the endeavour to develop nursing based on families'
      real needs.

PMID- 11820345
TI  - Post-operative epidural analgesia: introducing evidence-based guidelines through
      an education and assessment process.
AB  - The aim of this project was to re-introduce post-operative epidural analgesi on
      to two orthopaedic wards using an evidence-based practice approach. This was
      achieved through the provision of appropriate staff education and information,
      assessment of staff competence, and provision of relevant and appropriate staff
      support. An education programme was developed which included study days, ward
      based teaching and the assessment of competence. The introduction of guidelines
      followed an audit cycle in order to measure the success of the education
      programme. All nursing staff involved in the project were asked to complete a
      questionnaire which assessed their knowledge of caring for patients with
      postoperative epidural analgesia. This was completed before and following the
      education programme. The outcome measures were: (i) successful completion of
      competence-based assessment; (ii) levels of knowledge as assessed by the
      knowledge questionnaire; and (iii) participant perceptions of the project. The
      results of the questionnaire demonstrated significant improvements in knowledge
      following the education programme. Participants commented on the importance of
      the ward-based teaching. They also felt that pain was controlled more effectively
      using this method of analgesia.

PMID- 11820346
TI  - Nursing staff perceptions of the behaviour of older nursing home residents and
      decision making on restraint use: a qualitative and interpretative study.
AB  - This study examined staff perceptions of the behaviour of older nursing home
      residents and how these perceptions govern their decision making on restraint
      use. Data were collected in unstructured interviews with 20 trained and untrained
      nursing staff from two Swiss nursing homes. Data analysis was based on Colaizzi's
      phenomenological method. Two main themes were extracted from the data: (i)
      situations in which behaviour is perceived in terms of a problem that needs to be
      controlled and consequently leads to restraint use; and (ii) situations in which
      behaviour is perceived in terms of something one has to learn to live with and
      consequently leads to avoidance of restraint. Staff members' choices to perceive
      resident's behaviour from the angle they did were clearly associated with the
      rights and responsibilities of both nursing staff and older people. It is
      concluded that the primary source of change towards the avoidance of restraint
      use does not necessarily lie in external factors, but in staff members
      themselves.

PMID- 11820348
TI  - Clinical nurses as teachers: insights from students of nursing in their first
      semester of study.
AB  - This paper reports the findings of a study which sought to gain insights about
      the role of clinical nursing staff in the planned clinical experience of
      undergraduate nursing students. This study differs from others in that the
      perspectives of students of nursing in their first year of the undergraduate
      programme are sought, and the role of clinical nurses rather than clinical
      teachers is of particular interest. Using a story-telling approach, an
      exploration of students' perspectives on the role of clinical nursing staff in
      their clinical learning was undertaken. Analysis allowed findings to be grouped
      into helpful and unhelpful behaviours, Helpful behaviours included understanding
      and being friendly, showing interest and explaining. Behaviours that students
      found unhelpful to their learning were often passive rather than active, but they
      made students feel acutely aware of being unwelcome in the clinical area. Several
      students described feeling intrusive, uncomfortable and even unwelcome in
      clinical areas because o the attitudes and behaviour of clinicians. Findings of
      this study highlight the importance of clinicians and academic nurses working
      together to ensure that students of nursing, who represent the future of the
      profession, are provided with the best possible opportunities for clinical
      learning.

PMID- 11820347
TI  - Eating difficulties, need for assisted eating, nutritional status and pressure
      ulcers in patients admitted for stroke rehabilitation.
AB  - The aim of this study was to describe the types and extent of eating
      difficulties, the need for assistance when eating, the nutritional status and
      pressure ulcers in consecutive patients (n = 162) admitted for stroke
      rehabilitation over a period of 1 year. Structured observations and assessments
      of eating, nutritional status (subjective global assessment of nutritional
      status), pressure ulcers and activities in daily living (Katz ADL-index) were
      performed by a nurse who also trained the staff to perform these assessments.
      Difficulties in eating were found in 80%, and 52.5% were unable to eat without
      assistance. Eating difficulties were: 'eats three-quarters or less of served
      food' (60%), difficulties in 'manipulating food on the plate' (56%),
      'transportation of food to the mouth' (46%), 'sitting position' (29%), 'aberrant
      eating speed' (slow or forced) (26%), 'manipulating food in the mouth' (leakage,
      hoarding, chewing difficulties) (24%), 'swallowing difficulties' (18%), 'opening
      and/or closing the mouth' (16%), and 'alertness' (9%). Thirty-two percent were
      undernourished (49% of patients needing assisted eating and 13% of those not
      needing assistance, P < 0.0005). Among patients who were dependent in one or more
      functions according to the Katz ADL-index, 15% had pressure ulcers. The strongest
      eating variables for predicting nutritional status were 'alertness', 'swallowing
      difficulties', 'eats three-quarters or less of served food', and 'aberrant eating
      speed'. Nutritional status could in turn significantly predict pressure ulcers.
      Eating difficulties among patients with stroke are complex and the patient's
      situation before stroke adds to this complexity, especially among those dependent
      on assisted eating. As difficulties occur both among patients needing and not
      needing assisted eating, all patients with stroke admitted for rehabilitation
      need to be systematically assessed for eating difficulties and action needs to be
      taken to facilitate eating, especially as patients with eating difficulties risk
      becoming undernourished and in turn developing pressure ulcers.

PMID- 11820349
TI  - A discussion of the strengths and weaknesses of 'reflection' in nursing practice
      and education.
AB  - This paper begins by exploring the principles underpinning 'reflective practice'.
      The impact of reflection on the nursing profession is discussed, with particular
      attention being paid to nursing education. The value of reflective practice in
      nursing has been subject to considerable debate. This paper reviews both the
      claimed strengths and shortcomings of 'reflection', particularly in relation to
      the use of reflective material in the assessment of students.

PMID- 11820350
TI  - Supporting students in practice.
AB  - This article reports a project aiming to assess the effectiveness of clinical
      nurses employed in support roles for students in clinical practice in one UK
      higher education institution and its linked NHS Trusts. Focus groups and
      telephone interviews were used to collect data from the clinical support nurses
      themselves, senior nurse managers and pre- and post-registration students.
      Findings show that personal commitment to the role was high and that these
      support staff made a valuable contribution to up-to-date clinical input into
      classroom teaching. Managers also valued the university-clinical link role
      fulfilled by these staff. Students had mixed opinions, pre-registration students
      having had little exposure to this kind of support and post-registration students
      often not regarding clinical support as necessary because of their own existing
      clinical experience and expertise. For clinical support staff themselves, the
      role was a busy one and they often experienced conflict and role overload in
      balancing the education and clinical sides of their work. Necessary improvements
      for functioning of the roles were identified, including having regular meetings
      between university and NHS managers and support teachers for liaison purposes,
      joint appraisal, and formal support mechanisms for role occupants. The overall
      conclusion drawn is that the roles were successful in bridging the theory
      practice gap for the University and NHS Trust managers, but less so for students,
      and that they did this at some personal cost for role holders.

PMID- 11820351
TI  - The effect of a 3-year pre-registration training course on students' self-esteem.
AB  - Self-esteem is an acquired set of beliefs about the 'self' and is the largest
      determinant of behaviour. This study was carried out to identify changes in the
      self-esteem of students in order to assess the major influencing factors during
      their transition to becoming a nurse and to explore the interpretations and
      constructions which students ascribed to their experiences during this
      transition. Data were collected by the use of unstructured interviews. Analysis
      of data was qualitative, using a grounded theory method. Students' self-esteem
      became fragmented during the transition to becoming a nurse. The findings
      indicate a need to implement strategies to increase nurses' self-esteem.

PMID- 11820352
TI  - How do nurses deal with their emotions on a burn unit? A hermeneutic inquiry.

PMID- 11820353
TI  - When your patient can no longer live independently: a guide to supporting the
      patient and family.
AB  - This article uses a case study format to illustrate the Expanded Family Life
      Cycle Theory of Carter and McGoldrick (1999). This theory provides nurses and
      other health care providers with tools for assessing and planning care for older
      adults facing stressful life transitions. The individual and family are assessed
      as a unit embedded within their community. This multicontextual framework is
      applied to an elderly woman's transition from independent living to supervised
      living in a facility and illustrates the ease of use for practicing nurses.
      Suggestions are also offered to assist health care providers in supporting older
      adults and their families in making this significant transition.

PMID- 11820354
TI  - Delivering health information about self-medication to older adults: use of
      touchscreen-equipped notebook computers.
AB  - Preventing Drug Interactions in Active Older Adults is an educational
      intervention to prevent prescription and over-the-counter (OTC) drug and alcohol
      interactions in active, community-living older adults. The objectives of the
      program are to increase older adults' knowledge of potential interactions of
      prescription medications with OTC drugs and alcohol and to increase their
      confidence (self-efficacy) about how to avoid such interactions. An interactive
      multimedia computer software program (Personal Education Program or PEP) was
      designed for the learning styles and psychomotor skills of older adults. Focus
      groups of older adults evaluated PEP components in a formative manner during
      development. The program content dealing with antacids, calcium supplements, and
      acid reducers was pilot tested with 60 older adults recruited from local senior
      centers. Participants used the PEP on notebook computers equipped with infrared
      sensitive touchscreens. Users of PEP had greater knowledge and self-efficacy
      scores than controls. Participants indicated a high degree of satisfaction with
      the PEP and reported their intent to make specific changes in self-medication
      behaviors.

PMID- 11820355
TI  - Caregivers' perspectives of placement: implications for practice.

PMID- 11820356
TI  - This is Heaven's waiting room: end of life in one nursing home.
AB  - The purpose of this study was to describe the end of life in one midwestern
      nursing home from the perspective of residents who are chronically ill and
      declining, their family caregivers, and staff. Qualitative methods, including
      formal and informal interviews, participant observation, and health record
      abstraction, were used to describe the end of life for 13 nursing home residents.
      One dominating pattern, conflict, and five themes (i.e., communication, quality
      of life, staff education, teamwork, work environment) emerged as factors that
      influenced end-of-life care. The results of this study illustrate where and how
      problems within the nursing home industry, the participating nursing home, and
      between staff and residents influence and challenge care provided to dying
      residents.

PMID- 11820358
TI  - Not too confused to sing "God bless America".

PMID- 11820357
TI  - Conceptualizing resilience in women older than 85: overcoming adversity from
      illness or loss.
AB  - Resilience in women older than 85 is defined as the ability to achieve, retain,
      or regain a level of physical or emotional health after devastating illness or
      loss. This concept analysis of resilience in women older than 85 is based on the
      strategy suggested by Meleis. Resilience in women older than 85 is symbolized by
      a coiled wire, enclosed within a box similar to a jack-in-the-box. Environmental
      factors within the jack-in-the-box include frailty, determination, previous
      experience with hardship in learning how to cope, access to care, culturally
      based health beliefs, family support, self-care activities, caring for others,
      and functioning like efficiently working machines. External factors that
      influence the ability of the wire to recoil include the structure of the box
      itself and stress. More study is needed regarding diverse older women's
      experiences of resilience to develop a workable, clinically focused theory.

PMID- 11820359
TI  - Responding to the challenge for improved end-of-life care.

PMID- 11820360
TI  - Hearing screening.

PMID- 11820361
TI  - Bone-resorbing activity from cholesterol-exposed macrophages due to enhanced
      expression of interleukin-1alpha.
AB  - The presence of cholesterol crystals, macrophages, and foreign giant cells has
      been associated with impaired bone healing of periapical lesions. Therefore, we
      investigated whether macrophages exposed to cholesterol crystals can release
      factors changing the activity of bone-resorbing osteoclasts. Mouse peritoneal
      macrophages treated with cholesterol crystals in vitro produced factor(s) that
      stimulated the release of 45Ca and 3H from mouse calvariae pre-labeled with
      45Ca(CaCl2) or [3H]-proline, respectively. No bone-resorbing activity was
      released by epithelial cells, fibroblasts, or osteoblasts exposed to cholesterol
      crystals. Interleukin-1 receptor antagonist protein and antiserum neutralizing
      mouse interleukin-1alpha (IL-1alpha) inhibited 45Ca release induced by
      cholesterol-activated macrophages. The addition of cholesterol to the macrophages
      augmented the release of IL-1alpha protein and the expression of IL-1alpha mRNA.
      These findings indicate that frustrated phagocytosis by macrophages exposed to
      cholesterol crystals results in release of factors stimulating osteoclastic bone
      resorption, primarily due to increased transcription of the IL-1alpha gene.

PMID- 11820362
TI  - Regulation of TNF-alpha-induced IL-6 production in MG-63 human osteoblast-like
      cells.
AB  - Tumor necrosis factor-alpha (TNF-alpha) stimulates osteoblast production of
      interleukin-6 (IL-6), an inflammatory cytokine implicated in osteoclastic bone
      resorption. Therefore, we tested the hypothesis that TNF-alpha-induced IL-6
      production in MG-63 osteosarcoma cells occurs via the p38 mitogen-activated
      protein kinase (MAPK) pathway. TNF-alpha activated p38 MAPK and stimulated IL-6
      secretion by MG-63 cells, and pre-incubation of cells with the p38 MAPK inhibitor
      abrogated TNF-alpha-dependent IL-6 secretion. Transfection of IL-6 full-length
      and 5-deletion gene promoter reporter constructs indicated that p38 MAPK
      activation by TNF-alpha enhanced IL-6 gene expression, and that the p38 MAPK
      responsive region resided in the proximal 260-bp segment. Transfection of
      NFkappaB and C/EBPbeta-sensitive reporter promoter constructs demonstrated that
      NFkappaB activity was enhanced and that constitutive C/EBPbeta was inhibited by
      TNF-alpha, with both effects being p38 MAPK-dependent. In conclusion, although
      p38 MAPK activation by TNF-alpha stimulates IL-6 secretion by MG-63 cells, it has
      opposing effects on c/EBPbeta and NFkappaB activity.

PMID- 11820363
TI  - Interleukin-1alpha enhances type I collagen-induced activation of matrix
      metalloproteinase-2 in odontogenic keratocyst fibroblasts.
AB  - Interleukin-1alpha (IL-1alpha) is strongly expressed in odontogenic keratocysts.
      In this study, we investigated the effects of IL-1alpha on the activation of
      matrix metalloproteinase-2 (MMP-2) in the fibroblasts isolated from odontogenic
      keratocysts. Odontogenic keratocyst fibroblasts secreted a latent form of MMP-2
      (proMMP-2) spontaneously. Type I collagen induced the activation of the proMMP-2,
      and recombinant human IL-1alpha (rhIL-1alpha) further enhanced the type I
      collagen-induced activation of proMMP-2 in a dose-dependent manner. The rhIL
      1alpha-induced activation of proMMP-2 was inhibited by anti-human IL-1alpha
      antibody. A reverse-transcription/polymerase chain-reaction (RT-PCR) and Western
      immunoblotting demonstrated that the expression of membrane-type 1 matrix
      metalloproteinase (MT1-MMP) mRNA and protein was increased in the fibroblasts
      when the cells were cultured on type I collagen, and the expression was further
      enhanced by rhIL-1alpha. Thus, IL-1alpha may up-regulate proMMP-2 activation by
      increasing the expression of MT1-MMP in the fibroblasts isolated from odontogenic
      keratocysts synergistically with type I collagen.

PMID- 11820364
TI  - Spatial distribution of myosin heavy-chain isoforms in mouse masseter.
AB  - There is a paucity of information regarding the anatomy and muscle fiber
      phenotype of the masseter. The objective of this study was to characterize the
      distribution of each myosin heavy-chain (MyHC) isoform within different
      anatomical regions of male and female mouse masseters. Masseters from male and
      female CD-1 mice (2-4 months old) were examined for description of the anatomical
      partitioning of muscle fibers and endplate distribution. The spatial distribution
      of MyHC isoforms--embryonic, neonatal, slow, alpha-cardiac, IIa, and IIb--was
      determined within the defined masseter partitions by means of Western blot
      analysis and immunofluorescent localization. Types IIa, IIx, and IIb were the
      predominant MyHC isoforms observed. Distinct differences in the spatial
      distribution of these MyHC isoforms were found between muscle regions and varied
      between sexes. The regionalization of muscle fiber types in the mouse masseter is
      consistent with the functional compartmentalization of the masseter observed in
      other species.

PMID- 11820365
TI  - Neck motor unit activities induced by inputs from periodontal mechanoreceptors in
      rats.
AB  - Clinical evidence suggests that head movements may be coupled with oro-facial
      functions, which are predominantly controlled by somatosensory inputs from the
      oro-facial area. However, the effects of specific modalities of sensory inputs on
      the neck muscles' motor activity are still unclear. In the present study, natural
      pressure stimulation was applied to the rat's upper first molars, while motor
      unit electromyographic activity was recorded from the dorsal neck splenius
      muscle. During the hold phase of pressure stimulation, clear tonic discharges
      were elicited in the splenius muscles on both sides. Mean threshold values were
      622.3 mN (+/- 19.6 SEM, n = 39) and 496.8 mN (+/- 26.4 SEM, n = 43) for ipsi- and
      contralateral sides, respectively (p < 0.001, Mann-Whitney U test). Analysis of
      our data suggests that periodontal inputs may play an important role in
      controlling the motor activity of neck muscles, in addition to its well-known
      coordination of the masticatory function.

PMID- 11820366
TI  - Plasma membrane disruption in orthodontic tooth movement in rats.
AB  - Sublethal plasma membrane disruption (PMD) is an established mechanism for
      signaling in several cell types, including endothelial cells and skeletal muscle.
      We used a rat model of orthodontic tooth movement to test the hypothesis that
      periodontal ligament (PDL) cells communicate stretch to changes in bone cell
      activity in part via PMD. To produce PMD, we used a 50-g load from a spring
      activated in the buccal direction against the maxillary first molars for 5 min.
      Uptake of endogenous serum albumin was used as a PMD marker. Immunohistochemistry
      demonstrates albumin in PDL cells surrounding moved first molar tips. Image
      analysis shows significantly more albumin in cells of the buccal side (tension)
      of the moved teeth compared with those of the lingual, distal, and mesial sides,
      and those of the unmoved control. Albumin localization within cells of the PDL,
      after only 5 min of mechanical loading, suggests that PMD could promote uptake or
      release of signaling molecules.

PMID- 11820368
TI  - Decisions, decisions: challenges to the introduction of new technologies to
      clinical practice.

PMID- 11820367
TI  - Humans immunized with Streptococcus mutans antigens by mucosal routes.
AB  - Strategies aimed at the prevention of Streptococcus mutans infection and dental
      caries include mucosal immunization, which results in salivary anti-S. mutans
      responses. The purpose of this study was to evaluate the effectiveness of nasal
      vs. tonsillar immunization with S. mutans antigens in inducing salivary immune
      responses. Twenty-one adult subjects were immunized twice, within a seven-day
      interval, with a glucosyltransferase-enriched preparation (E-GTF) administered by
      nasal or tonsillar topical spray. Parotid saliva, nasal wash, and serum were
      collected prior to and at one- to two-week intervals for 3 months following
      immunization and were assayed by ELISA for anti-E-GTF activity. Results were
      analyzed by means of the mixed-models procedure with p < 0.05 level of
      significance. Significantly higher anti-E-GTF responses were detected in saliva
      and nasal wash samples from the group immunized by the nasal compared with the
      tonsillar route, indicating that nasal immunization was more effective in
      inducing mucosal responses in adults.

PMID- 11820369
TI  - Higher risk of preterm birth and low birth weight in women with periodontal
      disease.
AB  - Pregnant women with periodontal disease (PD) may be at increased risk for having
      preterm low-birth-weight (PLBW) children. We investigated whether the maintenance
      of the mothers' periodontal health after 28 weeks' gestation reduces the risk of
      PLBW. Of the 639 women studied, 406 had gingivitis and received treatment before
      28 weeks' gestation, and 233 had PD and were treated after delivery. Data about
      previous and current pregnancies and known risk factors were obtained from
      patients' medical records. Primary outcomes were delivery before 37 weeks'
      gestation or an infant with birth weight below 2500 g. The incidence of PLBW was
      2.5% in periodontally healthy women, and 8.6% in women with PD (p = 0.0004,
      relative risk = 3.5, 95% CI, 1.7 to 7.3). Risk factors significantly associated
      with PLBW were previous PLBW, PD, fewer than 6 pre-natal visits, and low maternal
      weight gain. PD was associated with both preterm birth and low birth weight,
      independent of other risk factors.

PMID- 11820370
TI  - Identification of cis-DNA regions controlling Bmp4 expression during tooth
      morphogenesis in vivo.
AB  - Epithelial-mesenchymal interactions are required for tooth formation. Bone
      morphogenetic protein 4 (Bmp4) is a crucial signaling molecule during this
      process. For better understanding of the role of the Bmp4 gene during tooth
      development, we studied the mechanisms that control its temporal and spatial
      expression during development. Using a transgenic approach, we determined that
      the domains which controlled Bmp4 expression in epithelium-derived ameloblasts
      were located in the region between 0.26 kb and 1.1 kb of the murine Bmp4
      promoter. In contrast, the domains controlling Bmp4 expression in mesenchyme
      derived odontoblasts and pulp cells existed in other regions of the Bmp4 gene. We
      have also demonstrated that the domains controlling Bmp4 expression in primordial
      tooth cells differ from those controlling Bmp4 expression in mature tooth
      tissues. The determination of unique domains by controlling the expression of the
      Bmp4 gene suggests that different transcriptional factors regulate the Bmp4 level
      at different stages during tooth morphogenesis.

PMID- 11820371
TI  - Elongated growth of octacalcium phosphate crystals in recombinant amelogenin gels
      under controlled ionic flow.
AB  - Amelogenin proteins constitute the primary structural entity of the extracellular
      protein framework of the developing enamel matrix. Recent data on the
      interactions of amelogenin with calcium phosphate crystals support the hypothesis
      that amelogenins control the oriented and elongated growth of enamel carbonate
      apatite crystals. To exploit further the molecular mechanisms involved in
      amelogenin-calcium phosphate mineral interactions, we conducted in vitro
      experiments to examine the effect of amelogenin on synthetic octacalcium
      phosphate (OCP) crystals. A 10% (wt/vol) recombinant murine amelogenin (rM179,
      rM166) gel was constructed with nanospheres of about 10- to 20-nm diameter, as
      observed by atomic force microscopy. The growth of OCP was modulated uniquely in
      10% rM179 and rM166 amelogenin gels, regardless of the presence of the
      hydrophilic C-terminal residues. Fibrous crystals grew with large length-to-width
      ratio and small width-to-thickness ratio. Both rM179 and rM166 enhanced the
      growth of elongated OCP crystals, suggesting a relationship to the initial
      elongated growth of enamel crystals.

PMID- 11820372
TI  - The extent to which resin can infiltrate dentin by acetone-based adhesives.
AB  - The combined methodologies of fractography and laser-Raman spectroscopic analysis
      were used for evaluation of the resin-dentin bonds made with wet and dry bonding.
      Resin-dentin-bonded beams were produced by means of 2 acetone-based adhesives
      (One-Step and Prime & Bond NT). The micro-tensile bond test was conducted, and
      the fractured surfaces of all specimens were examined by SEM and an image
      analyzer. The amount of resin infiltration within the hybrid layer was quantified
      by means of a laser-Raman spectroscope. In Raman analysis, the amount of resin
      impregnation within the hybrid layer of the dry bonding was found to be
      significantly lower (approximately 50%) than that in the wet one. Under
      fractographic analysis, a correlation was found between the bond strength and the
      failure mode. Based on those findings, it was suggested that the integrity
      between the bonding resin and the top of the hybrid layer played a major role in
      bond strength.

PMID- 11820373
TI  - Selecting patients for falls-prevention protocols: an evidence-based approach on
      a geriatric rehabilitation unit.
AB  - Geriatric rehabilitation treatment focuses on maximizing functional independence
      in older adults to facilitate a return to independent living following
      hospitalization. Rehabilitation professionals must therefore balance the need to
      foster increasing activity levels among patients while, at the same time,
      preventing falls and potential injuries. This study investigated measures of
      patient cognition and aspects of health as predictors of the risk for falls among
      geriatric rehabilitation patients. Fall rates and patient data were collected
      over an 18-month period. Data from 98 patients were included in the data set. The
      number of falls was regressed on the patient data to investigate their predictive
      power. Analyses were also conducted comparing fallers and nonfallers across the
      independent variables. Results revealed that the primary diagnosis was the only
      factor evidencing sufficient power for empirical identification of patients at
      the greatest risk for falls. The clinical implications of findings, in terms of
      an evidence-based approach to managing falls risk in this population, are
      discussed in this article.

PMID- 11820374
TI  - Studying fall risk factors among nursing home residents who fell.

PMID- 11820375
TI  - Older women change their minds about health.

PMID- 11820376
TI  - Falls and feelings: description of a psychosocial group nursing intervention.

PMID- 11820377
TI  - The effect of physical restraints on fall rates in older adults who are
      institutionalized.
AB  - Since the Omnibus Budget Reconciliation Act (OBRA) of 1987, there has been a
      significant reduction in the use of physical restraints to prevent falls in older
      adults who are institutionalized because of the developing awareness of the
      physical and psychological problems associated with them. The purpose of this ex
      post facto descriptive study was to determine if there is a difference in falls
      when physical restraints are allowed or prohibited in one older adult population.
      Data from incident reports from a purposive sample of 97 older adults in one long
      term care facility were analyzed before and after the implementation of a
      restraint-free policy. The results indicated no significant difference in the
      number of falls before and after the policy change. However, there was a
      significantly lower number of falls with injuries and a significantly higher
      number of falls without injuries. These findings suggest older adults will
      continue to fall with or without the use of physical restraints because of
      changes associated with the aging process and risk factors. Removing physical
      barriers from older adults and allowing freedom of movement may decrease the
      severity of injury sustained in a fall.

PMID- 11820378
TI  - Fall occurrence in a geriatric psychiatry setting before and after a fall
      prevention program.
AB  - A fall prevention program providing staff education, quantitative assessment of
      gait and balance, risk factors assessment, and evidence-based interventions was
      introduced on two geriatric wards of a regional psychiatric hospital. A within
      subjects comparison was made of fall occurrence during the 4-month pre
      intervention phase and the 4-month post-intervention phase using Fisher's exact
      test. Among those (N = 23) who survived the duration of the study, significantly
      fewer falls occurred in the post-intervention time period than in the pre
      intervention time period (p < 0.01). Comprehensive assessment, problem
      identification, and intervention planning by nurses may serve to reduce the
      number of falls among elderly individuals with severe psychiatric disorders.

PMID- 11820379
TI  - Falls: a more personal look.

PMID- 11820380
TI  - Evidence-based protocol: exercise promotion--encouraging older adults to walk.

PMID- 11820381
TI  - Surface electromyographic and electroglottographic studies in normal subjects
      under two swallow conditions: normal and during the Mendelsohn manuever.
AB  - Surface electromyography (EMG) has been used successfully in teaching patients
      swallow maneuvers in clinical settings. The present study aims to determine if
      surface EMG can reliably demonstrate differences in muscle activity between the
      normal swallow and the Mendelsohn maneuver and whether there is a close temporal
      relationship between submental muscles and laryngeal elevation as demonstrated by
      electroglottography (EGG). Surface EMG was measured from five muscle groups
      (superior and inferior orbicularis oris, masseter, submental and infrahyoid) in
      20 normal subjects under two swallowing conditions: normal and during performance
      of the Mendelsohn maneuver. A significant difference in EMG activity from the
      submental muscle group between the normal swallow and the Mendelsohn maneuver
      indicates that EMG at this location can be used reliably to differentiate between
      these two swallow conditions. The onset of submental activity and laryngeal
      elevation occurred within 10 ms of each other. The offset of submental activity
      and the return of the larynx to its resting position occurred within 24 ms of
      each other. Regarding the temporal relationship among the five muscle groups, the
      sequence of the most frequent muscle initiation was orbicularis oris inferior.
      orbicularis oris superior, masseter. submental muscle group, and infrahyoid
      muscle group. The sequence of the most frequent muscle termination was
      orbicularis oris superior, orbicularis oris inferior, masseter, submental muscle
      group, and infrahyoid muscle group in both normal swallow and the Mendelsohn
      maneuver.

PMID- 11820382
TI  - Vocal cord closure pressure during volitional swallow and other voluntary tasks.
AB  - Our goal was to determine and compare vocal cord (VC) closure pressure and its
      associated intratracheal pressure during several physiological events such as
      swallowing, coughing, straining, and phonation. We studied 11 healthy subjects
      (age 41 +/- 2 years) with no current or previous history of laryngeal or
      pulmonary diseases. VC closure pressure during the above-mentioned tasks was
      studied using a concurrent manometric and endoscopic technique. VC closure
      pressure during dry swallows averaged 298 +/- 23 mm Hg, while intratracheal
      pressures exhibited a biphasic pattern ranging from -4 +/- 0.5 to +6 +/- 0.8 mm
      Hg. Average VC closure pressure during cough was 280 +/- 20 mm Hg, during
      straining/valsalva maneuver it averaged 330 +/- 45 mm Hg, during phonation it
      produced an initial rapidly rising spike like pressure (222 +/- 25 mm Hg)
      followed by a sustained minimally positive pressure during continued phonation of
      two tested vowel sounds (15-25 mm Hg). Between-group comparison showed that for
      all studied tasks, the in-' tercordal pressures were significantly higher than
      those of respective intratracheal pressures (p < 0.05). The vocal cords generate
      closure pressures that vary depending on the performed function.

PMID- 11820383
TI  - Cardiovascular effects of the supraglottic and super-supraglottic swallowing
      maneuvers in stroke patients with dysphagia.
AB  - The prolonged voluntary closure of the glottis during the supraglottic and super
      supraglottic swallowing techniques may create the Valsalva maneuver. The Valsalva
      maneuver has been associated with sudden cardiac death and cardiac arrhythmias.
      This study describes the effects of the supraglottic and super-supraglottic
      swallowing techniques on the cardiovascular system. Subjects included 23 patients
      from an acute inpatient rehabilitation hospital. Subject groups included recent
      stroke, dysphagia. and a history of coronary artery disease (Group 1, N = 11).
      recent stroke and dysphagia with no known coronary artery disease (Group 2, N =
      4), and orthopedic diagnosis with no known dysphagia or coronary artery disease
      (Group 3, N = 8). Cardiac status was monitored for 4 hours during swallowing
      training, regular therapy sessions, and a meal. For Groups I and 2, 86.6% (13 out
      of 15) of the subjects demonstrated abnormal cardiac findings during the
      swallowing session including supraventricular tachycardia, premature atrial
      contractions, and premature ventricular contractions. Arrhythmia subsided within
      a few minutes after the session and did not occur during other activities. In
      Group 3 (control group), none of the subjects demonstrated abnormal cardiac
      findings except for bradycardia in one subject. It is suggested that the
      supraglottic and super-supraglottic swallow maneuvers may be contraindicated for
      patients with a history of stroke or coronary artery disease.

PMID- 11820384
TI  - Bolus consistency and swallowing in children and adults.
AB  - Research has shown that swallowing in adults is affected by bolus consistency.
      Little is known, however, regarding the effect of bolus consistency on swallowing
      in children. Electromyographic (EMG) data from typically developing five- and
      eight-year-old-children and adults were obtained from the following muscles as
      they swallowed boluses of different consistencies: (1) right upper lip, (2) right
      lower lip, (3) submental, and (4) laryngeal strap. Signal analyses included
      calculating EMG onset and offset and average EMG amplitude of muscle activity
      during swallowing. Findings revealed that by five years of age, children employ
      adultlike control strategies during swallowing: significant differences in
      duration and magnitude of muscle activity resulted as a function of bolus
      consistency. General observations revealed, however, that swallowing in children
      is characterized by muscle activity that is shorter in duration. Similarities and
      differences in the biomechanics of swallowing between children and adults are
      important to consider during clinical evaluations and treatment of children with
      dysphagia.

PMID- 11820385
TI  - Endoscopic diverticulotomy of Zenker's diverticulum: management and
      complications.
AB  - BACKGROUND: Two approaches can be used for treating Zenker's diverticulum
      operatively: external or endoscopic. METHODS: The records of 52 patients who
      underwent Zenker's diverticulum endoscopically were evaluated retrospectively.
      Twenty-two patients were treated with endoscopic scissors and 30 patients by
      carbon dioxide laser resection. The therapeutic concept of rigid endoscopic
      diverticulotomy was appraised with respect to the intraoperative and
      postoperative management for treatment and prevention of complications. RESULTS:
      Forty-four of 52 patients were free of symptoms and 8 patients (15.4%) had a
      recurrence, 4 of which were within 4 months. Except for 2 cases, the recurrences
      could be reoperated endoscopically. The complication rate was 13.5% with
      hemorrhage the most common complication (3 cases). Two cases required an external
      approach to control severe bleeding. CONCLUSIONS: The endoscopic approach for
      Zenker's diverticulum is safe and effective if the surgeon is prepared to handle
      extraordinary complications, such as severe hemorrhage, quickly and sufficiently.

PMID- 11820386
TI  - Effects of repeated wet and dry swallows in healthy adult females.
AB  - Understanding changes that may occur in the swallow with repetitive use in
      healthy individuals is a prerequisite to evaluate and treat persons with
      compromised swallowing. To determine any systematic effect of use on swallow
      function, we attempted to tax the swallow mechanism in a rigorous sequence of dry
      and liquid swallow conditions. Oropharyngeal temporal measures were assessed
      videofluoroscopically for 12 healthy females aged 20-29 during 42 wet and 5 dry
      swallows. No significant effects were found for any temporal measures over a
      series of 21 l-mL and 21 cup swallows plus 5 dry swallows, indicating swallow
      efficiency and safety do not appear to decline over 47 swallows in this young
      adult population. Additionally, no significant effects were found over the dry
      swallows or when 1-mL liquid swallows were compared with the dry, indicating dry
      swallows do not demonstrate significant change over a 5-swallow series due to
      reduced available saliva. Ability of subjects to perform consecutive dry swallows
      varied greatly. Results of this study provide normative data regarding multiple,
      consecutive, wet and dry swallowing in a healthy female population.

PMID- 11820388
TI  - Laryngopharyngeal dysmotility in multiple sclerosis.
AB  - This study investigated the swallowing physiology of 13 patients [age 27-69 years
      (mean = 45 years)] with multiple sclerosis (MS) who had Kurtzke Extended
      Disability Status Scale (EDSS) scores ranging from 2 to 9 (mean = 6) and who
      complained of difficulty swallowing. Videofluoroscopic recordings of the
      patients' calibrated liquid and paste bolus swallows were analyzed and compared
      with published normative data. Results showed that swallowing physiology was
      disordered in the 13 MS patients with severity level ranging from mild to severe.
      Eleven patients had primary pharyngeal dysphagia. 1 patient had primary laryngeal
      dysphagia, and 1 patient had primary oral dysphagia. Laryngeal dysmotility, the
      predominant anterior pharyngeal segment dysfunction, was evidenced in all 13
      patients with MS. They displayed significantly longer-than-normal pharyngeal
      delay times, shorter-than-normal time intervals from onset of laryngeal excursion
      to return to rest. and longer-than-normal time intervals between airway closure
      at the arytenoid to epiglottic base and upper esophageal sphincter opening.
      Pharyngeal constrictor dysmotility, the predominant posterior pharyngeal segment
      dysfunction, was observed in 11 of the 13 MS patients. A significant relationship
      was found between the severity of the MS patients' functional swallowing
      impairment and posterior pharyngeal segment dysfunction. Material penetrated the
      supraglottic airway of 9 patients with 1 patient aspirating. A significant
      relationship was observed between supraglottic penetration and brainstem
      dysfunction. No significant relationship was found between severity of dysphagia
      and neurological disability as measured by EDSS scores or neurological impairment
      as measured by Functional System (FS) scores. Disturbed neuromotor sequencing of
      laryngeal events and a progression in neuromotor weakening of the pharyngeal
      constrictors were suggested from the findings.

PMID- 11820387
TI  - Epiglottic dysfunction: abnormal epiglottic movement patterns.
AB  - Epiglottic movement patterns of 500 consecutive patients with varying etiologies
      were recorded during routine videofluoroscopic swallow evaluations. Seven
      distinct, commonly repeated, abnormal epiglottic patterns were identified. A
      multifactorial analysis of these seven abnormal epiglottic movement patterns was
      completed. Findings indicate that each of these seven distinct movement patterns
      have varying rates and amounts of aspiration. A description of each epiglottic
      movement pattern is given in conjunction with information regarding aspiration
      and other variables associated with the swallow process. A universal nomenclature
      is offered regarding these subtle abnormal epiglottic movement patterns to
      increase a verbal commonality in our descriptions of epiglottic function as it
      affects aspiration.

PMID- 11820389
TI  - Case report: botulinum toxin in hypertensive lower esophageal sphincter: a
      manometric case study.
AB  - The hypertensive lower esophageal sphincter (HLES) is a disorder of esophageal
      motility associated with dysphagia and chest pain. Although well characterized
      manometrically, opinions differ greatly with regard to its pathophysiology and
      its management. Therapy is limited to a few medications, esophageal dilatation,
      and even surgery, although none of these options are consistently successful. In
      this case report we describe a 54-year-old woman with HLES and dysphagia who was
      successfully treated with botulinum toxin injection of the lower esophageal
      sphincter (LES). Esophageal manometry after botulinum toxin therapy revealed
      normalization of LES pressures. Three months after therapy, symptoms returned and
      repeat esophageal manometry demonstrated the return of elevated LES pressures.
      This report is the only published case of botulinum toxin injection into the LES
      with both pre- and post-treatment esophageal manometric data. This case report is
      evidence that LES dysfunction produces symptoms in patients with HLES, and that
      reduction in LES pressure improves symptoms. Current pathophysiologic hypotheses
      for HLES-associated dysphagia and its treatment are briefly reviewed in this
      report.

PMID- 11820390
TI  - Review of reports on relative prevalence of swallowing disorders after acute
      stroke (Dysphagia 16:141-142, 2001).

PMID- 11820391
TI  - Counterion-induced actin ring formation.
AB  - Actin filaments form rings and loops when > 20 mM divalent cations are added to
      very dilute solutions of phalloidin-stabilized filamentous actin (F-actin). Some
      rings consist of very long single actin filaments partially overlapping at their
      ends, and others are formed by small numbers of filaments associated laterally.
      In some cases, undulations of the rings are observed with amplitudes and dynamics
      similar to those of the thermal motions of single actin filaments. Lariat-shaped
      aggregates also co-exist with rings and rodlike bundles. These polyvalent cation
      induced actin rings are analogous to the toroids of DNA formed by addition of
      polyvalent cations, but the much larger diameter of actin rings reflects the
      greater bending stiffness of F-actin. Actin rings can also be formed by addition
      of streptavidin to crosslink sparsely biotinylated F-actin at very low
      concentrations. The energy of bending in a ring, calculated from the persistence
      length of F-actin and the ring diameter, provides an estimate for the adhesion
      energy mediated by the multivalent counterions, or due to the streptavidin-biotin
      bonds, required to keep the ring closed.

PMID- 11820392
TI  - Mossbauer study of iron centers in D1/D2/Cyt b559 complexes isolated from
      photosystem II of spinach.
AB  - Mossbauer spectroscopy was applied to study the properties of cytochrome b559
      (Cyt b559) in isolated D1/D2/Cyt b559 preparations (from spinach) that are
      completely deprived of non-heme iron. In these samples, all Cyt b559 exists as
      low-potential form(s) with the iron center attaining the low-spin ferric state in
      the absence of a strong reductant. The Mossbauer spectra were analyzed using
      isomer shift and quadrupole splitting parameters below 100 K, gathered from an
      extrapolation of the temperature dependence of experimental data of photosystem
      II membrane fragments from spinach. The calculations, based on the Griffith
      model, lead to the conclusion that the crystal field around the heme iron of Cyt
      b559 is characterized by a strong rhombic distortion. The g-values obtained are
      in agreement with recently published EPR results. The use of an extended
      theoretical approach permits the description of the relaxation changes of the
      Mossbauer spectra in the temperature region from 5 K to 60 K. It shows that the
      environment of the heme iron in D1/D2/Cyt b559 is not homogeneous but most likely
      reflects the existence of two different forms. We assume that factors other than
      changes of the first coordination sphere are responsible for the drastic negative
      shift in the redox potential of Cyt b559 that takes place during the isolation
      procedure of D1/D2/Cyt b559 complexes. Possible implications of these findings
      are discussed.

PMID- 11820393
TI  - Fractal dimension of K1735 mouse melanoma clones and spheroid invasion in vitro.
AB  - An in vitro tumour-host confrontation method to investigate the invasion
      behaviour of cancer has been applied to K1735 mouse melanomas. Fluorescently
      labelled spheroids of cancer cells and host cells were confronted and the
      temporal course of cancer invasion into the host was investigated using confocal
      laser scanning microscopy. To improve the quantitative data of this method, the
      boundary images of the fluorescently labelled confrontation pairs were treated as
      fractals. The physical and mathematical framework for determination of the
      fractal capacity dimension is widely used in biology and medicine and has proved
      to be a very useful tool for describing the cancer invasion process. The fractal
      capacity dimension determination was carried out by dilation of the binary
      boundaries of the objects, which were treated as an estimate of the Minkowski
      Bouligand dimension. The fractal dimension correlated well with the degree of
      invasion of the K1735-M2 clone. Control experiments, with host-host
      confrontations and various K1735 clones with reduced invasiveness, support these
      results.

PMID- 11820394
TI  - Quantitative analysis of cardiac electrical restitution.
AB  - Electrical restitution (ER) of cardiac cells is an aggregate of events that
      rhythmically restore the initial conditions of electric signal (action potential)
      generation. Its analysis represents an important insight into cardiac
      arrhythmogenesis. The aim of this work is to theoretically substantiate and
      verify a novel approach allowing for the quantification of the individual ionic
      current components of ER. A method of analysis of the primary, initial conditions
      setting restitution processes (apart from the secondary, test pulse-affected
      ones) is proposed. Both processes are described as sums of their measurable
      constituents. It is demonstrated that the optimum parameter of ER is the electric
      charge that is transferred through ionic channels and carriers during the test
      impulse. The theory was tested by using voltage-clamped canine ventricular
      preparations and by computer simulations. The experimental ER curve of canine
      ventricular muscle was constructed using action potential (AP) plateau voltage
      and half-repolarization time as parameters. At 30 degrees C and 0.5 Hz
      stimulation, the ER curve peaked, on average, after 400 ms with a 10% overshoot.
      Of this plateau elevation, 50% was due to 4-aminopyridine-sensitive transient
      outward current and 44% was due to verapamil-sensitive current. The delayed
      outward current antagonized the overshoot by about 6%. It was found that the
      initial conditions (i.e. the primary restitution processes) tend to strongly
      alter the plateau voltage of the premature AP. However, the final deviation is by
      about one order less. It is concluded that the voltage-dependent secondary
      processes counteract the effect of the primary processes, thereby suggesting
      strong negative feedback control of natural APs.

PMID- 11820395
TI  - Assignment of charge movements to electrogenic reaction steps of Na,K-ATPase by
      analysis of salt effects on the kinetics of charge movements.
AB  - Na,K-ATPase-enriched membrane fragments adsorbed to lipid bilayers were used to
      study electrogenic Na+ movements induced by enzyme phosphorylation when ATP was
      photo-released from inactive caged ATP, and simultaneously by externally applied
      alternating voltages which allowed the measurement of small ATP-induced membrane
      admittance changes. A detailed analysis of frequency dependence of the
      capacitance and conductance increments showed that the observed process consists
      of more than one electrogenic step. The frequency dependence could be described
      by the sum of two Lorentzian functions and a constant term. The faster process
      (approximately 2000 s(-1)) was assigned to the release of the first extracellular
      Na+ ion. The corner frequency of the slower Lorentzian (about 30 s(-1)) coincided
      with the reciprocal exponential time constant of the falling phase of the
      transient current, which can be assigned to the conformational transition.
      Preferentially, the slower process showed a dependence on the ion concentration
      of choline salts with different anions. The effectiveness of the used chaotropic
      anions to decelerate the kinetics decreased in agreement with the Hofmeister
      series, I- > Br- > Cl-. This observation matches their effect on the partition
      between two phosphoenzyme states of the Na,K-ATPase, as established previously.

PMID- 11820396
TI  - Molecular simulation of the interaction of kappa-conotoxin-PVIIA with the Shaker
      potassium channel pore.
AB  - Molecular simulation techniques were appplied to predict the interaction of the
      voltage-dependent Shaker potassium channel with the channel-blocking toxin kappa
      conotoxin-PVIIA (PVIIA). A structural thee-dimensional model of the extracellular
      vestibule of the potassium channel was constructed based on structural homologies
      with the bacterial potassium channel Kcsa, whose structure has been solved by X
      ray crystallography. The docking of the PVIIA molecule was obtained by a
      geometric recognition algorithm, yielding 100 possible conformations. A series of
      residue-residue distance restraints, predicted from mutation-cycle experiments,
      were used to select a small set of a plausible channel-toxin complex models among
      the resulting possible conformations. The four final conformations, with similar
      characteristics, can explain most of the single-point mutation experiments done
      with this system. The models of the Shaker-PVIIA interaction predict two clusters
      of amino acids, critical for the binding of the toxin to the channel. The first
      cluster is the amino acids R2, I3, Q6 and K7 that form the plug of the toxin that
      interacts with the entrance to the selectivity filter of the channel. The second
      cluster of residues, R22, F23, N24 and K25, interacts with a channel region near
      to the external entrance of the pore vestibule. The consistency of the obtained
      models and the experimental data indicate that the Shaker-PVIIA complex model is
      reasonable and can be used in further biological studies such as the rational
      design of blocking agents of potassium channels and the mutagenesis of both
      toxins and potassium channels.

PMID- 11820397
TI  - An analysis of the relationship between fatty acid composition and the lamellar
      gel to liquid-crystalline and the lamellar to inverted nonlamellar phase
      transition temperatures of phosphatidylethanolamines and diacyl-alpha-D-glucosyl
      glycerols.
AB  - The lamellar gel to lamellar liquid-crystalline (Lbeta/Lalpha) and lamellar
      liquid-crystalline to inverted hexagonal (Lalpha/H(II)) phase transitions of a
      number of phosphatidylethanolamines (PEs) and diacyl-alpha-D-glucosyl-sn
      glycerols (alpha-D-GlcDAGs) containing linear saturated, linear unsaturated,
      branched or alicyclic hydrocarbon chains of various lengths were examined by
      differential scanning calorimetry and low-angle X-ray diffraction. As reported
      previously, for each homologous series of PEs or alpha-D-GlcDAGs, the
      Lbeta/Lalpha phase transition temperatures (Tm) increase and the Lalpha/H(II)
      phase transition temperatures (Th) decrease with increases in hydrocarbon chain
      length. The Tm and the especially the Th values for the PEs are higher than those
      of the corresponding alpha-D-GlcDAGs. For PEs having the same effective
      hydrocarbon chain length but different chain configurations, the Tm and Th values
      vary markedly but with an almost constant temperature interval (deltaT(L/NL))
      between the two phase transitions. Moreover, although the Tm and Th values of the
      PEs and alpha-D-GlcDAGs are equally sensitive on the temperature scale to
      variations in the length and chemical configuration of the hydrocarbon chains,
      the deltaT(L/NL) values are generally larger in the PEs and vary less with the
      hydrocarbon chain structure. This suggests that the PE headgroup has a greater
      ability to counteract variations in the packing properties of different
      hydrocarbon chain structures than does the alpha-D-GlcDAG headgroup. With
      decreasing chain length, this ability of the PE headgroup to counteract the
      hydrocarbon chain packing properties increases, significantly expanding the
      temperature interval over which the Lalpha phase is stable relative to the
      corresponding regions in the alpha-D-GlcDAGs. Overall, these findings indicate
      that the PEs have a smaller propensity to form the H(II) phase than do the alpha
      D-GlcDAGs with an identical fatty acid composition. In contrast to our previous
      report, there is some variation in the d-spacings of these various PEs (and alpha
      D-GlcDAGs) in both the Lalpha and H(II) phases when the hydrocarbon chain
      structure is changed while the effective chain length is kept constant. These
      hydrocarbon chain structural modifications produce different d-spacings in the
      Lalpha and H(II) phases, but those changes are consistent between the PEs and
      alpha-D-GlcDAGs, probably reflecting differences in the hydrocarbon chain packing
      constraints in these two phases. Overall, our experimental observations can be
      rationalized to a first approximation by a simple lateral stress model in which
      the primary bilayer strain results from a mismatch between the actual and optimal
      headgroup areas and the primary strain in the H(II) phase arises from a simple
      hydrocarbon chain packing term.

PMID- 11820398
TI  - Conserved guanine-guanine stacking in tetraplex and duplex DNA.
AB  - Using a series of suitably chosen oligonucleotides, we demonstrate that the DNA
      duplex of d(CCCCGGGG) provides an almost identical CD spectrum as the parallel
      stranded tetraplex of d(GGGG). The CD spectra are very sensitive to base stacking
      in DNA so that the above observation indicates that guanine-guanine stacking is
      essentially the same within the duplex of d(CCCCGGGG) and the tetraplex of
      d(GGGG). A very similar CD spectrum is also provided by the A-form of d(CCCCGGGG)
      induced by trifluoroethanol. These results reveal that guanine-guanine stacking
      is a structural invariant conserved in various nucleic acid conformers. The
      structural invariance is likely to cohere with evolution of the genetic molecules
      and be important for fundamental functions, e.g. initiation of transcription.

PMID- 11820399
TI  - Immunohistochemical demonstration of Leu-7 (HNK-1), Neurone-specific Enolase
      (NSE) and Protein-Gene Peptide (PGP) 9.5 in the developing camel (Camelus
      dromedarius) heart.
AB  - The development of the heart-conducting system has been controversially
      discussed. The common opinion that these specialized myocytes originate from
      mesodermal precursors has been challenged when nerve-specific antigens (Leu-7,
      NF, GIN2) were demonstrated in embryonic hearts of various species, suggesting a
      neural crest contribution to the embryonic conducting tissue. Anti-Leu-7 (HNK-1)
      antibodies were reported to reliably mark the conducting system in developing
      rat, chicken and human hearts. The present investigation was carried out on the
      hearts of 15 camel fetuses at 35, 45, 60, 75 and 100 cm crown-rump length (three
      specimens for each stage), in addition to three adult hearts. We investigated the
      antigenicity of cardiac structures for Leu-7, NSE (Neurone specific Enolase) and
      PGP (Protein Gene Peptide) 9.5. In all specimens investigated, both NSE and PGP
      9.5 were expressed by cardiac nerves and conducting system components. The
      sinuatrial and atrioventricular nodes, the atrioventricular bundle as well as
      subendocardial and intramyocardial Purkinje fibers were stained. In contrast, the
      developing conducting system did not react with anti-Leu-7 antibody, although Leu
      7 antigenicity was strongly expressed by the developing cardiac nerves. In adult
      camel hearts, the same pattern of immunoreactivity for the markers studied was
      still retained. Our results show that the expression of marker proteins for the
      developing conducting system is species-specific. Therefore, these markers are of
      little significance in discussions on the possible neurogenic nature of the heart
      conducting tissue.

PMID- 11820400
TI  - Ultrastructural features in the epididymis of the dog (Canis familiaris, L.).
AB  - The ultrastructure of the epididymal duct of the dog is described in this paper.
      The epididymis was divided into three morphofunctional segments: initial, middle
      and terminal. The cellular population of the lining epithelium is formed from
      principal, apical, basal and clear cells. The peritubular stroma and the tubular
      interstitium surrounding the epithelium are also described. The outcome is
      compared to the description made in other species of mammals.

PMID- 11820401
TI  - Lipolysis and ultrastructural changes of intracellular lipid vesicles after
      cooling of bovine and porcine GV-oocytes.
AB  - The aim of our investigation was to compare the ultrastructure of lipid droplets,
      and the effect of cooling on intracellular lipid vesicles of bovine and porcine
      GV oocytes. The lipid droplets in bovine GV oocytes have a homogeneous structure.
      The utilization of lipids takes place directly from these vesicles without
      formation of interim lipid compounds. In contrast, there are two kinds of lipid
      droplets in porcine GV oocytes: 'dark', homogeneous vesicles next to 'grey'
      vesicles with electron-lucent streaks. Vesicles of each specific group are
      connected to each other. After a 12-h culture, the formation of the cisternal
      smooth endoplasmic reticulum layer was always associated with 'grey' lipid
      vesicles. This is evidence that during oogenesis lipolysis takes place only in
      'grey' vesicles. It is supposed that cytoplasmic lipolysis has two stages: 'dark'
      vesicles change into a 'grey' form followed by a utilization of these 'grey'
      lipids. Furthermore, both types of lipid droplets in porcine oocytes changed
      morphologically during cooling: they changed into a spherical form with lucent
      streaks. Lipid droplets in bovine GV oocytes revealed no visible morphological
      changes after cooling.

PMID- 11820402
TI  - Immunocytochemical analysis of vimentin expression patterns in porcine embryos
      suggests mesodermal differentiation from day 9 after conception.
AB  - The expression of the intermediate filament proteins vimentin and keratin in
      porcine embryos was studied by whole-mount immunocytochemistry between day 7 and
      day 11 after conception. Expression of vimentin was first detected in the inner
      cell mass of about 50% of the 9-day-old embryos. In elongated 11-day-old embryos,
      cells expressing vimentin were observed in the epiblast (after disappearance of
      Rauber's membrane) and in cells migrating from the epiblast between the
      trophoblast and the underlying hypoblast layer. A keratin-positive response was
      observed in trophectoderm cells at all stages. These findings suggest that inner
      cell mass cells in the pig start differentiating into mesodermal cells not later
      than day 9 after conception. While the delamination of the mesodermal germ layer
      is known to correlate with the loss of pluripotency of the inner cell mass cells,
      the early onset of mesodermal differentiation in the porcine embryo,
      characterized by vimentin expression and in contrast to the mouse, could in part
      be responsible for the lack of success in establishing pluripotent embryonic stem
      cell lines in this species. Our results suggest that further attempts to isolate
      inner cell mass-derived pluripotent cells should be attempted well before day 9
      after conception.

PMID- 11820403
TI  - Carbohydrate histochemistry of the alimentary canal of the shi drum, Umbrina
      cirrosa L.
AB  - Histochemical staining techniques, which differentiate the main categories of
      carbohydrates, were applied to sections from different segments of the alimentary
      canal of the shi drum Umbrina cirrosa L. to study patterns of distribution of
      epithelial glycoconjugates. In the oesophagus, mucous cells contained
      sulphomucins, together with a small amount of sialomucins. Stomach epithelial
      cells secreted neutral and acidic glycoconjugates, while gastric glands only
      produced small quantities of sialomucins. Goblet cells showed the presence of
      sialo and sulphomucins in the pyloric caeca, whereas intestinal mucous cells
      secreted sulphated glycoconjugates. This work serves as a baseline for further
      studies on carbohydrate composition of the mucosa of the shi drum digestive
      system.

PMID- 11820404
TI  - Structural and ultrastructural characteristics of interrenal gland and chromaffin
      cell of matrinxa, Brycon cephalus Gunther 1869 (Teleostei-Characidae).
AB  - This work presents the structure and ultrastructure of the interrenal gland and
      chromaffin cells, as well as the morphology of the head kidney of Brycon
      cephalus. The head kidney is composed of fused bilateral lobes located anterior
      to the swim bladder and ventrolateral to the spinal column. The parenchyma
      revealed lympho-haematopoietic tissue, melano-macrophage centres, interrenal
      gland and chromaffin cells. The interrenal gland consisted of cords or strands of
      cells grouped around the posterior cardinal vein and their branches. Chromaffin
      cells are found in small groups, closely associated with the interrenal gland
      and/or under the endothelium of the posterior cardinal vein. So far, the
      ultrastructural analysis has revealed only one interrenal cell type which
      contained abundant smooth endoplasmic reticulum and numerous mitochondria with
      tubulo-vesicular cristae, characteristic of steroid-producing cells. Two types of
      chromaffin cells were observed. The first type was characterized by the presence
      of vesicles with round, strongly electron-dense granules, which were
      eccentrically located. Such cells were interpreted as noradrenaline cells.
      Meanwhile, cells which contained smaller vesicles and electron-lucent granules,
      with a small halo separating the granule from the vesicular limiting membrane,
      were identified as adrenaline cells.

PMID- 11820405
TI  - An explanation of a groove found on the nasal process of the equine incisive
      bone.
AB  - Thirteen fresh equine heads were dissected in an attempt to determine the cause
      of a groove frequently found on the dorsal border and medial side of the nasal
      process of the incisive bone. This groove appeared on both sides in 40 out of 44
      equine skulls. The sulcus seems to be caused by the combined action of the
      lateralis nasi muscle and the medial accessory cartilage of the nose (cartilago
      nasalis accessoria medialis). Other sulci found on the nasal process of the bone
      may be explained as impressions caused by nerves.

PMID- 11820406
TI  - Lingual ultrastructure of the long-finned pilot whale (Globicephala melas).
AB  - Microscopic studies on the cetacean tongue are limited and, to date, only a few
      ultrastructural reports on dolphins have been published. This report presents the
      initial description of the lingual ultrastructure of the long-finned pilot whale.
      The lingual integumental surface was smooth, lacking papillae, although flaking
      of outer stratum corneum cells could be observed at high resolution. The
      keratinocytes of the stratum spinosum of the epidermis resembled those of
      cetacean skin on other regions of the body. The similarities included the
      presence of cytoplasmic lipid droplets around the nuclei of stratutm spinosum
      cells, a lingual feature not seen in terrestrial mammals. Keratin intermediate
      filaments were numerous and occasionally formed aggregates of circular whorls. At
      cell surfaces, bundles of keratin intermediate filaments were frequently observed
      inserting into desmosomal plaques. Pigment granules were not evident and
      organelles were sparse. Stratum corneal cells contained nuclear remnants
      (parakeratosis) and small multivesicular bodies, and the corneal layer was
      approximately 18 cells thick. The nuclei of the stratum basale keratinocytes
      possessed exceptionally numerous and deep clefts. The dermis was nondistinctive.
      The skeletal muscle of the tongue was arranged in widely separated fasiculi
      containing small numbers of muscle fibres. Typical fine structure of skeletal
      muscle bands and tubular elements was observed by transmission electron
      microscopy.

PMID- 11820407
TI  - Histological and histochemical studies on the lingual, preglottal and laryngeal
      salivary glands of the Japanese quail (Coturnix coturnix japonica) at the post
      hatching period.
AB  - The postnatal development and histochemistry of mucins of the lingual, preglottal
      and laryngeal glands in the quails were investigated by means of light microscopy
      using specific staining for complex carbohydrates. In this study, the tongues
      were taken from female and male quails from day 1 to day 60 after hatching. The
      salivary glands in quail's tongue comprised the lingual gland, with lateral and
      medial (paraentoglossal gland) portions that differ in morphology and
      histochemical staining, and the preglottal gland, with two lateral portions and
      one medial portion. The medial portion of the preglottal gland, which extended to
      the row of the laryngeal papillae on each side of the glottis, was described as
      the laryngeal gland. The salivary glands were present at hatching and their cells
      were functionally mature and secreted mucins. In quail of all ages, the
      histochemical reactions revealed that the cytoplasms of the secretory cells of
      the preglottal, laryngeal and paraentoglossal gland (medial portion of lingual
      gland) contained sialomucins and weakly sulphated epithelial mucins. Neutral
      mucins were absent in the paraentoglossal gland, while a small amount of neutral
      mucins was present in other glands. The mucins with vicinal diol groups,
      sialomucins and weakly sulphated epithelial mucins were mixed within the
      secretory cells of all the glands. All the histochemical reactions were
      restricted to the supranuclear regions of the secretory cells within the lateral
      portion of the lingual gland. In conclusion, the contents of mucins in the
      lingual, preglottal and laryngeal glands varied between different age groups,
      however, no differences in the glands' histochemistry between male and female
      quails were observed.

PMID- 11820408
TI  - Immunohistochemical localization of inhibin subunits in the testis of the bull.
AB  - The differential localization of the inhibin beta subunits betaA and betaB in the
      testis of adult bull was studied using specific monoclonal and polyclonal primary
      antibodies. Inhibin betaA- and betaB-subunits were localized only in the Sertoli
      cells. The inhibin betaA-subunit was observed in the cytoplasm while the betaB
      subunit was localized in the nucleus. No specific findings depending on
      spermatogenic stages were observed among the seminiferous tubules. Moreover, the
      inhibin alpha-subunit was not detected in the testis of the bulls. In addition,
      no inhibin subunits were detected in the Leydig cells and spermatogenic cells.
      These findings indicate the presence of betaA- and betaB-subunits in the bull,
      which may suggest a possibility that activin is produced and/or stored in the
      Sertoli cells and regulates spermatogenesis in an autocrine/paracrine manner.
      Moreover, the inhibin betaB-subunit may be produced in the nucleus but the
      functional meaning of this is not yet clear.

PMID- 11820409
TI  - Double aortic arch in a dog (Canis familiaris): a case report.
AB  - We herein report a case of a double aortic arch in a 10-week-old male dog of no
      defined race, which presented episodes of regurgitation at the time of weaning.
      This vascular malformation was characterized by the persistence of two aortic
      arches, right and left, of varying dimensions. The right aortic arch was observed
      to be larger. During post mortem examination the vessels of the animal were
      injected with coloured latex bi-centrifuged CIS 1-4 polisopreno which revealed
      the patency of the two aortic arches. Concomitantly, dilation of the cranial
      oesophagus causing constriction was observed, indicating megaesophagus. Apart
      from the constriction, the oesophagus presented normal morphometric parameters in
      relation to its dimensions.

PMID- 11820410
TI  - Removal of liver tumours using radiofrequency waves.
AB  - In the treatment of early and intermediate hepatocellular carcinoma the range of
      indications for percutaneous ablation techniques is becoming wider than surgery
      or intra-arterial therapies. Although it is understood that partial resection
      assures the highest local control, the survival rates after surgery are roughly
      comparable with those obtained with PEI or RF ablation. The explanation is due to
      a balance among advantages and disadvantages of the two therapies. Survival
      curves with percutaneous ablation techniques are better than curves of resected
      patients who present adverse prognostic factors, and this means that surgery
      needs a better selection of the patients. Indications for both of therapies are
      reported. An open question remains the choice among different ablation
      procedures. In our department we currently use RF ablation in the majority of
      patients but consider PEI and segmental TACE complementary, and use them
      according to the features of the disease and the response. In the treatment of
      colorectal metastases, the initial survival curves of RF ablation are promising.
      As treatment is size and site dependent, partial resection remains the gold
      standard. However, on the basis of the studies on "test of time", a possible
      candidate could be a patient presenting operable lesions with favourable criteria
      for a complete ablation. An interesting indication seems to be the treatment of
      breast liver metastases in selected patients.

PMID- 11820411
TI  - Assessing the severity of truncal gunshot wounds: a nation-wide analysis from
      Finland.
AB  - BACKGROUND AND AIMS: Gunshot wounds of the chest and abdomen are potentially life
      threatening, but there is a great variation in their actual severity emphasising
      the importance of accurate severity assessment for prehospital decision-making,
      clinical management and outcome prediction. The purpose was to analyse the
      severity of truncal gunshot injuries from a nation wide data base during a 5-year
      period with comparison to a previous 5-year period, and to assess the ability of
      the New Injury Severity Score (NISS) in comparison with the "old" Injury Severity
      Score (ISS) in predicting short-term morbidity. MATERIAL AND METHODS: Based on
      the National Hospital Discharge Register, 199 patients admitted for truncal
      gunshot wounds in Finland during 1990-4 were identified and their hospital
      records analysed. RESULTS: Of the 199 truncal gunshot wounds, 146 (73%) were
      caused by low, 16 (8%) by high-energy bullets and 37 (19%) by shotgun blasts.
      Sixty-seven patients (34%) had wounds, which did not enter the thoracic or
      abdominal cavity. Nonoperative management including wound surgery and placement
      of a chest tube was possible in 86% of the thoracic wounds, 13% of the
      thoracoabdominal and 19% of the abdominal wounds. The overall mortality and
      morbidity rates were 2% and 23%, respectively. In comparison to the previous 5
      year period, there was a 47% increase in total and 67% increase in truncal
      gunshot wound admissions. The presence of cavitary penetration (positive
      predictive value 31% and negative predictive value 93% for morbidity), the ISS
      and the NISS scores were all statistically significant (p = 0.000 in all
      categories) predictors of hospital morbidity and length of stay. CONCLUSIONS: The
      admission rate for gunshot wounds in Finland is increasing. A large proportion of
      patients can be managed nonoperatively and the overall outcome is very good. Both
      ISS and NISS scores can be used to predict hospital morbidity and length of stay
      with little benefit in replacing ISS with NISS. The assessment of cavitary
      penetration is useful and has a high negative predictive value for short-term
      morbidity.

PMID- 11820412
TI  - Role of laparoscopy and laparoscopic ultrasound in staging of pancreatic tumours.
AB  - BACKGROUND AND AIMS: Radiological imaging alone is not reliable enough in staging
      of pancreatic cancer. Not only because of poor sensitivity but also because there
      is a tendency to overstage tumours. The aim of the study was to compare the
      efficiency of spiral computed tomography (CT), transabdominal ultrasound (US),
      laparoscopy (LAP) and laparoscopic ultrasound (LUS) in staging of pancreatic
      tumours. MATERIAL AND METHODS: In this prospective study 27 patients underwent
      pancreatic tumour staging with CT, US, LAP and LUS. The reference standard was
      operative evaluation or in case of disseminated disease laparoscopic assessment.
      RESULTS AND CONCLUSIONS: Although LAP was hindered by adhesions in 11% of the
      patients the benefit of LAP staging was evident in detecting peritoneal
      carcinomatosis. The assessment of the local tumour expansion of a pancreatic
      carcinoma was difficult for all staging modalities. LUS did not change the
      decision whether to proceed with laparotomy once. In our experience routine use
      of laparoscopic staging does not benefit patients with pancreatic tumour but in
      selected cases it may prevent unnecessary laparotomy.

PMID- 11820413
TI  - The dilemma of suspicious urine cytology in patients being followed for bladder
      cancer.
AB  - BACKGROUND AND AIMS: Urine cytology is gold standard for clinical tests used in
      the diagnosis and follow-up of bladder cancer. Cytology, however, exhibits
      variable sensitivity depending on tumour grade and interpretation of urine
      specimens is highly dependent on the skill of the examiner. Furthermore, a
      "suspicious" cytology report (class III) makes clinicians uncomfortable. In these
      cases, a more objective test, such as the BTA stat Test, may be useful in
      providing clarification. The aim of this study was to evaluate the dilemma of
      suspicious routine urine cytology and to determine whether the BTA stat Test
      provides diagnostic aid in this rare but controversial category. MATERIAL AND
      METHODS: 506 consecutive patients who were being followed for bladder cancer were
      included in the study. A voided urine sample was obtained prior to routine follow
      up cystoscopy and split for culture and testing with the BTA stat Test. Clinical
      status of the disease was evaluated in patients with suspicious urine cytology,
      and the diagnostic aid of the BTA stat Test in these patients was determined.
      RESULTS: A total of 57 patients (11.3%) had urine cytology classified as
      suspicious. The BTA stat Test was positive in 29 (50.9%) and negative in 28
      (49.1%) patients. Nineteen (33.3%) patients had recurrence at routine cystoscopy.
      Of the remaining 38 patients, 10 were further investigated due to a positive BTA
      stat Test. Two additional recurrences were detected bringing the total number of
      recurrences to 21 (36.8%), 48.3% (14/29) of the patients with positive and 25.0%
      (7/28) of the patients with negative BTA stat Test had recurrence (p = 0.069).
      Overall, 65.5% (19/29) of the patients with a positive BTA stat Test were found
      to have recurrence either at routine cystoscopy, at further investigations, or at
      the next cystoscopy compared to that of 35.7% (19/28) in those with negative
      testing (p = 0.024). The overall sensitivity of the BTA stat Test was 66.7%, and
      the specificity was 58.3%. CONCLUSIONS: At least a third of the patients under
      follow-up for bladder cancer with suspicious cytology had a recurrence,
      indicating that these patients are a risk group for recurrence. More importantly,
      a BTA stat Test result seems to provide some help in distinguishing those
      patients with very high risk for recurrence, for whom invasive further
      investigations should be conducted and a close follow-up policy maintained.

PMID- 11820414
TI  - Routine follow-up cystoscopy in detection of recurrence in patients being
      monitored for bladder cancer.
AB  - BACKGROUND AND AIMS: Cystoscopy and urine cytology are the standard tools for
      monitoring superficial bladder cancer. The sensitivity of cystoscopy is, however,
      limited to the tumours that can be visualised, and the sensitivity of cytology is
      relatively low in low-stage/low-grade tumours. Therefore, new tumour markers have
      been developed. BTA stat has been reported to have high sensitivity in detecting
      both primary and recurrent bladder tumours, and may have the potential to detect
      tumours that cannot be visualised by routine cystoscopy including recurrences in
      upper tract. The objective of the study was to analyse the reliability of routine
      follow-up cystoscopy by further investigating patients with positive marker
      status, BTA stat Test and urine cytology, but negative cystoscopy. MATERIAL AND
      METHODS: 446 consecutive patients being followed for bladder cancer were analysed
      in a prospective multicenter study. A voided urine sample was obtained prior to
      cystoscopy and split for culture, cytology and BTA stat testing. In the case of
      positive marker status, BTA stat Test or urine cytology, but negative cystoscopy
      patients were further investigated by i.v. urography or renal ultrasound and
      random biopsies. The sensitivity of routine follow-up cystoscopy is reported.
      RESULTS: Of 446 patients 131 (29.4%) had a bladder cancer recurrence at routine
      cystoscopy. Of the remaining 315 patients not having recurrent tumour at
      cystoscopy, 56 patients (17.8%) had positive BTA stat Test result, 6 (1.9%) had
      positive cytology and 5 were positive by both tests. Nine recurrences that were
      missed at routine follow-up cystoscopy were detected by further investigations
      making the total number of bladder confined recurrent tumours 140 (140/446,
      31.4%). Five of these 9 recurrences were high grade lesions (1 T1G3, 4 CIS), of
      which 4 were detected by positive cytology. The overall sensitivity of cystoscopy
      was 93.6%. CONCLUSIONS: We found that routine follow-up cystoscopy may miss over
      five percent of the recurrent tumours. Although cystoscopy remains the gold
      standard for bladder cancer follow-up, it is suggested that even with negative
      cystoscopy patients with positive marker status, BTA stat Test and especially
      urine cytology, should be considered at risk for coexisting, and in some case
      even high grade recurrence.

PMID- 11820416
TI  - Bone healing models in rat tibia after different injuries.
AB  - AIMS: Gradual elaboration of an adequate and efficient multistage method for
      experimental remodelling of specific wound healing process--bone repair.
      Comparison of clinical characteristics with the results of microanatomy,
      histology, electronmicroscopy and computer morphometry. MATERIAL AND METHODS: An
      investigation of posttraumatic bone repair after internal fracture, excision and
      cortical perforation was carried out on 142 young adult male Wistar rats. The
      repair was studied in normal and affected animals (exercises, immobilization,
      isolation of periost) at 1-42 days after operation. RESULTS: The posttraumatic
      bone callus development and the related soft tissue repair, likewise the
      continuous remodelling, is an ordinary process of osteohisto- and organogenese.
      In trained rats the blood supply and bone formation is increased, whereas in
      immobilized animals it is inhibited and destroyed (osteoporose, pseudoarthrosis).
      After the injury some characteristics of bone repair histogenese will be became
      evident (after the perforation the primary endosteal and secondary periosteal
      ossification, inhibition of endosteal bone repair after the isolation of periost
      etc.). CONCLUSION: The posttraumatic bone healing, like embryohistogenese, has
      similar repair stages in all models of the experiments as well as similar tissue
      and cell responses (callus formation, its replacement, bone remodelling, etc.).
      However, the repair process in general (order of chondrous and/or bone callus
      stages, etc.) is variable and dependent on the mode and degree of injury. The use
      of bone cortex perforation in wound healing study is more recommendable as
      compared to internal fracture and excision (possibility of in situ study the
      periost and callus tissue compartments in bone repair machinery separately).

PMID- 11820415
TI  - Bursting strength and collagen content changes in esophageal anastomoses.
      Comparative experimental study in dogs.
AB  - BACKGROUND AND AIMS: The Biofragmentable Anastomosis Ring (BAR) is a mechanical
      device composed of absorbable material, performs an inverted anastomosis by
      atraumatic compression. It is a safe method recommended for bowel ends covered by
      serosal layer. The feasibility for esophageal surgery hasn't been proved. In our
      study we compared the healing of transsected intrathoracic esophagus anastomosed
      with BAR versus Stapler on an experimental dog model by evaluating the bursting
      strength (BS) and collagen (Hydroxyproline (HP)) concentration and content in
      different sites and defined time points after surgery (4th, 7th, 14th, 28th day).
      MATERIAL AND METHODS: Forty-six mongrel dogs were randomly separated into two
      groups (28 BAR, 18 Stapler) and parameters of surgical repair evaluated after
      sacrification on certain days. RESULTS: Although we had a total of 4 leaks
      (14,3%) only in the BAR group (2 were clinically relevant and fatal), there was
      no significant difference in the leakage rate between the two groups. BS was
      significantly higher in the BAR group during the first week with values almost
      equal from the 14th day, in both groups. BS measurement reflects anastomotic
      strength only during the first two postoperative weeks. After this rupture is
      often produced outside the anastomotic line. HP concentration showed no
      significant differences from samples taken next to and far from the anastomotic
      line. The HP rate showed a significant reduction in the 4th and 7th day
      subgroups, and values close to the reference from the 14th day with both
      techniques. CONCLUSIONS: BS and HP changes proved a normal tissue repair with no
      significant difference, showing that both methods are suitable to perform
      anastomoses on the intrathoracic esophagus in mongrel dogs. The higher mechanical
      stability of the BAR anastomosis could suggest the feasibility of the method in
      conditions where higher mechanical strength is requested.

PMID- 11820417
TI  - A prospective comparison between external fixation and plates for treatment of
      midshaft nonunions of the clavicle.
AB  - BACKGROUND AND AIMS: Several surgical techniques have been used to treat
      clavicular nonunions. The aim with this prospective study was to compare
      treatment of symptomatic midshaft clavicular nonunions with either external
      fixation or plating. PATIENTS AND METHODS: The study included two consecutive
      series where the first 11 patients (8 men and 3 women) were treated with external
      fixation (EF) while the following 13 patients (5 men and 8 women) were treated
      with internal fixation using a 3.5 mm reconstruction plate (RP). All patients had
      autologous cancellous bone graft. After on average 8.6 years (EF) and 5.4 years
      (RP), respectively, an independent observer evaluated the patients. RESULTS: In
      the EF-group 8/11 healed within 12 months while 3/11 healed after reoperation
      with a reconstruction plate and new bone grafting at 6-9 months. In the RP-group
      12/13 healed within six months while 1/13 healed after two additional bone
      transplants. There was no hardware breakage. The healing time for the RP group
      was significant shorter when compared with the EF group even if the fractures
      that did not heal after the first operation were excluded. In 4 patients the
      plate was removed following healing. There was no significant difference in
      functional outcome between groups at follow up. CONCLUSION: The reconstruction
      plate was a better alternative than external fixation due to faster and more
      reliable healing. Patients commonly considered the external frame cumbersome.

PMID- 11820418
TI  - Longevity of the Marshall-Marchetti-Krantz procedure.
AB  - BACKGROUND AND AIMS: The Marshall-Marchetti-Krantz procedure (MMK) is a vesico
      urethral suspension, for the correction of urethral hypermobility in women with
      stress urinary incontinence. This study aims to describe the long-term outcome of
      the procedure. MATERIAL AND METHODS: 40 women with stress incontinence underwent
      the MMK. All operations were performed by one surgeon. Analysis of patients'
      notes yielded the early continence rate and perioperative morbidity. Long-term
      outcome was measured by means of a postal questionnaire with telephone contact to
      ensure maximum uptake. RESULTS: The immediate continence rate was 82%. Continence
      rates at up to 22 years follow-up (mean 8.5 years) is 61%. All failures occurred
      within 2 years of the operation. CONCLUSION: Patients still continent two years
      after the MMK will maintain continence in the long-term.

PMID- 11820419
TI  - Changing pattern of major lower limb amputations in Seinajoki Central Hospital
      1997-2000.
AB  - BACKGROUND AND AIMS: There is rather limited recent information on major
      amputations in Finland. Our objective was to describe the incidence of major
      lower limb amputations in a defined central hospital, the demographic
      characteristics of the amputees, diagnosis and situations leading to amputation,
      level of amputations and survival of the amputees after one year. MATERIAL AND
      METHODS: A retrospective study was undertaken on 156 patients with 169 lower limb
      major amputations from 1997 to 2000 at the Seinajoki Central Hospital and Ahtari
      District Hospital. RESULTS: The annual incidence of major amputations reduced
      from 29.5 to 15.2/100000 inhabitants. The mean age of the patients was 78.5 years
      but highest 80.1 in the year 2000. The reason for major amputation was chronic
      critical leg ischaemia with or without diabetes mellitus in 79.1% and acute
      ischaemia in 13.9%. The average below-knee (BK)/above-knee (AK) amputation ratio
      was 0.80 during the years 1997-1999 and the ratio was lowest 0.67 in year 2000.
      At the same year 2000 the amount of patients, whose condition was too poor for
      reconstructive surgery, was significantly higher than in 1997-1999. CONCLUSIONS:
      We suggest that BK/AK amputation ratio is decreasing in the future as the
      amputees tend more often to be institutionalized and immobile, and reconstruction
      is not an alternative and BK amputation is impossible or useless.

PMID- 11820420
TI  - Flutter valve drainage bag is a useful device for the pleural drainage.
AB  - BACKGROUND AND AIMS: The purpose of the present study was to compare the use of
      the flutter valve pleural drainage bag and the conventional underwater seal
      system for the pleural drainage in the treatment of pneumothorax and pleural
      effusion. PATIENTS AND METHODS: Altogether fifty patients who needed the pleural
      drainage at our hospital between February and October 1999 were randomized to
      this prospective study either into the flutter valve pleural drainage group or
      into the conventional underwater seal pleural drainage group, 25 patients in
      each. RESULTS: In the conventional underwater seal system group, the mean
      drainage time was 4.1 (SD +/- 4.0) days and in the flutter valve drainage bag
      group 4.8 (SD +/- 4.9) days (difference -0.7, 95% confidence interval (CI) -3.3
      to 1.8). The mean length of hospitalization was 16.3 (SD +/- 20.9) days and 18.7
      (SD +/- 27.0) respectively (difference -2.4, 95% CI -16.1 to 11.3). CONCLUSIONS:
      The results of this study suggest that flutter valve drainage bag is a safe and
      feasible system in the most cases when pleural drainage is needed in the
      treatment of pneumothorax and pleural effusion.

PMID- 11820421
TI  - Penetration of Ullevaal hip screw into the pelvis.
AB  - The fracture of the femoral neck is usually treated operatively with screw
      osteosynthesis or prosthesis. There have been reported a rare complication both
      with screws and lag screws used in hip fractures, both can penetrate into the
      pelvis postoperatively. We present two cases with this similar rare complication
      when using Ullevaal screws. Both patients were reoperated on with a total hip
      arthroplasty (THA). We think that the exact anatomical reposition and good
      operation technique should make this complication even more rare. The canal
      should always be drilled only to the line of the fracture, so that there is no
      canal for the screw to squeeze further. To prevent penetration some kind of cap
      fixed the lateral end of the screw could also be worth while.

PMID- 11820422
TI  - The importance of different procedures for different indications in sympathetic
      surgery.

PMID- 11820423
TI  - Amplitude and target diameter in motor programming of discrete, rapid aimed
      movements: Fitts and Peterson (1964) and Klapp (1975) revisited.
AB  - The reports by Fitts and Peterson [J. Exp. Psychol. 67(2) (1964) 103-113] and
      Klapp [J. Exp. Psychol. Hum. Percept. Perform. 104(2) (1975) 147-153] concerning
      the effects of movement amplitude and target diameter on reaction time present
      conflicting results. Fitts and Peterson reported that reaction time increased
      when movement amplitude was lengthened. Klapp reported an interaction in which
      target diameter effect on reaction time was moderated by movement length: for
      small targets, reaction time decreased with increasing movement length but
      reaction time remained unchanged (or increased modestly) when target diameter was
      large. Two experiments were conducted to replicate and examine the inconsistency
      in the reaction time results. For both experiments movement time results were in
      agreement with the predictions of Fitts' law. However, the results for reaction
      time were mixed: support was obtained for Klapp (1975) but not for Fitts and
      Peterson (1964). Further analysis identified several potential variables that
      could have influenced reaction time and explained the different effects on
      reaction time reported by Fitts and Peterson (1964) and Klapp (1975). The
      potential variables could include: limb posture at the start of a response;
      number of limb segments required to perform the task; and the effect of pooling
      reaction time data from targets located right and left of the start point, and
      from near and far targets.

PMID- 11820424
TI  - The impact of anticipated action effects on action planning.
AB  - Three experiments with a total of 72 participants investigated the assumption
      that motor actions are planned in terms of their sensorial effects. Participants
      had to prepare a certain action A that consistently led to a sensorial effect (a
      tone of certain pitch). Instead of (in Experiment 1) or before (in Experiments 2
      and 3) the execution of the prepared action, another response B had to be carried
      out, which either resulted in the same or in a different auditory effect (a tone
      of same or different pitch). It was found that a to-be-executed response B was in
      general initiated more quickly when it resulted in the same effect as a
      concurrently prepared response A. The results are considered as evidence for the
      basic notion that the preparation and initiation even of very simple actions is
      mediated by an anticipation of their reafferences.

PMID- 11820425
TI  - A comparison of AME and CR100 for scaling perceived exertion.
AB  - In psychophysical studies of the relation between perceived magnitude and
      physical stimulus, interest has focused on the preciseness of growth functions.
      Very little interest has been devoted to natural levels of an "absolute"
      character and to the validity of direct measurements. In this article, the
      Category (C)-Ratio (R) (CR) scaling methodology, developed by Borg (1973, 1977,
      1982) is presented together with a new CR scale: the CR100 scale. In an
      experiment on perceived exertion, CR100 was compared with Absolute Magnitude
      Estimation (AME). Perceived exertion has the advantage of having easily measured
      physiological variables that can function as validity criteria. 32 persons (16
      men and 16 women) participated as subjects on two different occasions, and the
      presentation order was counterbalanced. Results from CR100 and AME could be
      described equally well with psychophysical functions. The exponents obtained with
      CR100 were n = 1.60 for women and n = 1.69 for men, and the corresponding
      exponents for AME were n = 1.60 for women and n = 1.46 for men (with a "noise"
      constant included in the function). ANOVA showed that CR100 could make the
      predicted differentiation between sexes, whereas AME could not. This drawback
      with AME was also found when using the methods to predict working capacity.

PMID- 11820426
TI  - Influence of practice on response-selection and response-implementation processes
      involved in the response-interference effect.
AB  - In a choice reaction-time task, the response-interference effect is an increase
      in reaction times when the two possible responses are from the same hand compared
      to when the two possible responses are from different hands [Psychonomic Science
      2 (1965) 55-56; Human Motor Control, Academic Press, San Diego, CA, 1991].
      Although the influence of practice on other reaction-time effects (i.e., the
      complexity effect and precuing) has been examined, research evaluating the
      influence of practice on the response-interference effect is limited. Therefore,
      two experiments were conducted to determine the influence of practice on the
      response-interference effect. In Experiment 1, a bilateral transfer task was used
      to assess the influence of practice on the response-selection processes
      associated with the response-interference effect. The practice results indicated
      decreased reaction times, but did not influence the response-interference effect.
      In Experiment 2, a priming task was used to assess the influence of practice on
      response-implementation processes associated with the response-interference
      effect. The reaction time results indicated a change in the response-interference
      effect. The results of these two experiments suggest that with only two fingers
      on response keys, practice alters the mechanical constraints affecting the
      response-implementation processes and thereby decreases the response-interference
      effect.

PMID- 11820427
TI  - Effects of spatial attention on detection and identification of oriented lines.
AB  - In this paper, we study the effects of spatial attention on detection and
      identification of oriented lines presented at near-threshold luminance. In the
      first experiment, we found that the cuing effect was greater when observers had
      to discriminate between two close orientations than when they had to discriminate
      between two far-apart orientations. In the second experiment, we examined the
      effects of peripheral cues on summation of low-contrast oriented lines. We found
      that the range of orientations within which summation occurred was greater when
      the cues were invalid than when they were valid. Our results suggest that
      attention to a specific location in the visual field modulates the neural
      channels which code orientation in at least two different ways: (a) spatial
      attention increases the responsivity of these channels to stimuli presented at
      this location, and (b) it reduces the bandwidths or ranges of orientations to
      which these channels are sensitive. These results suggest that the properties of
      the orientation-tuned channels, including those that seem to exert their effects
      at early stages of orientation processing (e.g., tuning function), may not be
      fixed, but rather vary according to the attention being paid to the spatial
      region within which the target stimulus is presented.

PMID- 11820428
TI  - Stimulus motion and retrospective time judgments.
AB  - The effect of stimulus motion on retrospective time judgments was investigated in
      four experiments. Subjects reproduced the duration of a 32-s interval which was
      filled by either a stationary or moving visual element presented on a computer
      monitor. In Experiments 1 and 4, the element moved horizontally back and forth,
      and in Experiments 2 and 3 it traced a circular pathway. In Experiments 1 and 2,
      the element moved at speeds of either 5 or 20 cm/s. In Experiment 3, it moved at
      a constant speed, alternating direction between clockwise and anti-clockwise
      rotation once every 1, 4, 8 or 16 s. In Experiment 4 the element moved at linear
      speeds of 1, 2, 4, 8 or 16 cm/s back and forth along a 16 cm horizontal path
      thereby alternating between left- and rightward motion-directions once every 16,
      8, 4, 2 and 1 s, respectively. Temporal reproductions were not systematically
      influenced by stimulus speed. Rather, the pattern of results indicated a
      nonmonotonic relationship between remembered duration and the frequency of motion
      direction changes; whereas remembered duration was unaffected by either
      infrequent or very frequent rates of changes, moderate rates of motion-changes
      lengthens remembered duration. These findings are discussed in relation to the
      change models of retrospective timing, and the claim that stimulus speed, as
      distinct from changes in the direction of stimulus motion, is not an important
      determinant of retrospective timing.

PMID- 11820429
TI  - Protistology today: advances in the microbial eukaryotic world.

PMID- 11820430
TI  - Exploring Leeuwenhoek's legacy: the abundance and diversity of protozoa.
AB  - Towards the end of the 17th century, Leeuwenhoek built "magnifying glasses" that
      enabled him to see and describe protozoa for the first time. Continued
      exploration of the natural history of protozoa during the past 300 years has
      progressed far beyond simply documenting morphospecies (global total probably
      <20,000). We now realize that protozoan 'biodiversity' is multi-faceted (e.g.
      sibling species, variant genotypes and syntrophic consortia). Realization of
      their extraordinary abundance has secured for protozoa the position of dominant
      phagotrophs and regenerators of nutrients within microbial food webs. And studies
      of protozoa in the natural environment have done much to effect a paradigm shift
      in our understanding of why specific microbes live where they do and how they got
      there in the first place. In particular, the hypothesis of ubiquitous dispersal
      of protozoan species does seem to be supported by the evidence provided by
      morphospecies, sibling species and even individual genotypes.

PMID- 11820431
TI  - Enzymatic systems of inorganic pyrophosphate bioenergetics in photosynthetic and
      heterotrophic protists: remnants or metabolic cornerstones?
AB  - An increasing body of biochemical and genetic evidence suggests that inorganic
      pyrophosphate (PPi) plays an important role in protist bioenergetics. In these
      organisms, two types of inorganic pyrophosphatases [EC 3.6.1.1, namely soluble
      PPases (sPPases) and proton-translocating PPases (H+-PPases)] that hydrolyse the
      PPi generated by cell anabolism, thereby replenishing the orthophosphate pool
      needed for phosphorylation reactions, are present in different cellular
      compartments. Photosynthetic and heterotrophic protists possess sPPases located
      in cellular organelles (plastids and mitochondria), where many anabolic and
      biosynthetic reactions take place, in addition to H+-PPases, which are integral
      membrane proteins of the vacuolysosomal membranes and use the chemical energy of
      PPi to generate an electrochemical proton gradient useful in cell bioenergetics.
      This last category of proton pumps was considered to be restricted to higher
      plants and some primitive photosynthetic bacteria, but it has been found recently
      in many protists (microalgae and protozoa) and bacteria, thus indicating that H+
      PPases are much more widespread than previously thought. No cytosolic sPPase (in
      bacteria, fungi and animal cells) has been shown to occur in these lower
      eukaryotes. The widespread occurrence of these key enzymes of PPi metabolism
      among evolutionarily divergent protists strongly supports the ancestral character
      of the bioenergetics based on this simple energy-rich compound, which may play an
      important role in survival under different biotic and abiotic stress conditions.

PMID- 11820432
TI  - Intracellular bacteria in ciliates.
AB  - Ciliates are frequently colonized by other micro-organisms. The large size of
      ciliate cells offers habitats for hundreds to thousands of bacteria in different
      compartments, such as cytoplasm, nuclei and even perinuclear spaces. Size,
      phagocytic feeding habit and other features appear to be favorable pre
      adaptations of ciliates for symbiosis with bacteria. Certain intracellular
      bacteria are permanent symbionts that are not infectious, whereas others are
      highly infectious. Both types show specific adaptations. With their wide spectrum
      of phylogenetic positions, intracellular bacteria in ciliates show relationships
      to different taxa of free-living bacteria and even archaea. Certain symbionts may
      be deleterious for their host ciliates, whereas others may provide a selective
      advantage under appropriate conditions or even be essential for the host cells.
      Depending on the nature of a symbiont, its prevalence in a host population may be
      low or high. Symbionts that express a killer toxin affecting non-infected
      ciliates achieve high infection rates in a host population. whereas certain
      infectious bacteria may only show a low prevalence.

PMID- 11820433
TI  - Ciliate cryptobiosis: a microbial strategy against environmental starvation.
AB  - This review outlines the main features of ciliate resting-cyst formation or
      encystment. It represents a strategy against several environmental stresses (such
      as starvation), which involves a highly gene-regulated cell differentiation
      process and originates a more resistant, differentiated form or resting cyst.
      This process is mainly characterized by drastic cytoplasmic dehydration that
      induces a general metabolic rate decrease, intense autophagic activity, the
      formation of a permeable cyst wall protecting the cell against the adverse
      environmental conditions, and a gene-silencing mechanism after opening the
      specific encystment genes.

PMID- 11820434
TI  - ABC transporters in the protozoan parasite Leishmania.
AB  - ATP-binding cassette (ABC) transporters constitute one of the biggest and most
      conserved protein families in the evolutionary scale. Many of them are of
      enormous clinical relevance, due to their relationship with genetic diseases and
      drug resistance during the treatment of cancer and infectious diseases.
      Leishmaniasis is a major and globally widespread group of parasitic diseases,
      whose treatment has been complicated by the expansion of resistance to
      conventional drugs. Here, we review the current knowledge about ABC transporters
      in Leishmania spp, with special attention to their relationship with the drug
      resistance phenotype.

PMID- 11820436
TI  - Ramon y Cajal, a pioneer in science fiction.

PMID- 11820435
TI  - Unusual characteristics of ciliate actins.
AB  - Actin is a cytoskeletal protein that is ubiquitous in eukaryotes, hence the
      corresponding genes and proteins have been isolated from numerous organisms as
      different as animals, plants, fungi and protozoa. Several atomic models are
      available for the monomeric as well as the filamentous form, and more than 70
      proteins that bind actin and control filament dynamics have been isolated from
      diverse eukaryotes. Moreover, the function and dynamics of the actin cytoskeleton
      in several eukaryotic systems have been depicted in depth. Unlike other protozoa,
      such as amoeba, actin is not an abundant protein in ciliates, whose cytoskeleton
      is mainly composed of microtubular arrays. Ciliate actin has been studied in
      several species, and it was established early on that this ciliate protein is
      very different from that of other eukaryotes. Similarly, the actin-binding
      proteins studied in ciliates display great differences with those of other
      eukaryotes. Consequently, ciliate actin has been considered as "unconventional,"
      and this review focuses on molecular data leading to this conclusion.

PMID- 11820437
TI  - Experimental epiphysiodesis: magnetic resonance imaging evaluation with
      histopathologic correlation.
AB  - We performed an experimental epiphysiodesis on the tibia in 16 immature New
      Zealand white rabbits. The purpose was to study the process of trauma-induced
      growth plate closure. The animals were killed at weekly intervals over 8 weeks.
      We correlated the histological findings with serial magnetic resonance images.
      The undamaged, central part of the growth plate became histologically abnormal
      within 1 week. Mature bone bridge formation in the area of the epiphysiodesis was
      seen after 3 to 4 weeks. The study suggests that growth arrest starts before the
      bone bridge formation. Factors regulating cartilage growth may also play a role.

PMID- 11820438
TI  - The cytotoxic effect of methotrexate loaded bone cement on osteosarcoma cell
      lines.
AB  - We mixed various amounts of methotrexate with bone cement and measured the
      absorbance daily for 4 weeks. The cytotoxic effects on SaOS2 and MG63
      osteosarcoma cells were examined by the MTT assay, and analysed according to the
      methotrexate concentration and the elapsed time. The amount of eluted
      methotrexate was greatest during the first day, and then decreased rapidly
      reaching a plateau in the third week. The number of viable tumour cells decreased
      significantly after 72 h, and they were hardly seen after 1 week.

PMID- 11820439
TI  - Hip fractures in Finland and Great Britain--a comparison of patient
      characteristics and outcomes.
AB  - All hip fracture patients (age <50 years, pathological and subtrochanteric
      fractures excluded) were registered at admission to hospital and at 4 months
      (mortality up to 1 year) between 1989 and 1997 in Peterborough District Hospital
      (2083 patients) and Oulu University Hospital (1702 patients). The mean age at
      fracture was 80.3 years in Peterborough and 78.3 years in Oulu. Respectively, 69%
      and 62% of the patients had been living in their own homes, 50% and 54% had been
      able to walk alone unassisted. In Oulu, the patients were discharged after a mean
      stay of 7.1 days, most of them to health care centre hospitals (71%) and only 21%
      to their original place of residence. In Peterborough 81% were discharged to
      their original place of residence after a mean stay of 15.6 days. At 4 months,
      54% were living at their own homes in Peterborough and 44% in Oulu. The overall
      mortality at 1 year was 27.1% in Peterborough and 24.9% in Oulu.

PMID- 11820440
TI  - Lengthening osteotomy at the intertrochanteric level with simultaneous correction
      of angular deformities.
AB  - Fixed multiplane deformities around the hip representing a combination of
      rotational, angular, and leg-length discrepancies are disabling for the patient
      and pose a challenge for the orthopaedic surgeon. We describe a joint-preserving,
      one-stage procedure to address these complex problems using an intertrochanteric
      osteotomy with a step-cut to allow for corrective lengthening, angulation, and
      rotation. We present our results in nine patients. The aim of this paper is to
      provide the orthopaedic surgeon with a detailed approach to treating these
      deformities with reproducible results.

PMID- 11820441
TI  - Failure of intertrochanteric fracture fixation with a dynamic hip screw in
      relation to pre-operative fracture stability and osteoporosis.
AB  - We have reviewed 178 intertrochanteric fractures treated by dynamic hip screw
      (DHS) fixation between March 1995 and December 1999 and followed for a minimum of
      1 year. We used Singh's classification of the trabecular bone structure in the
      proximal femur as a measure of osteoporosis and also classified the fractures
      according to three different systems (Boyd-Griffin, Evans, AO). The postoperative
      radiographs were examined for loss of reduction, i.e. varus angulation >100,
      perforation of the femoral head, more than 20-mm extrusion of a lag screw or
      metal failure. We found 49 cases which showed radiographic failures. Two were
      stable fractures and 47 unstable fractures (Evans' classification). Unstable
      fractures with osteoporosis had a failure rate of more than 50%. In such cases
      DHS should not be the first choice for treatment.

PMID- 11820442
TI  - Valgus intertrochanteric osteotomy for neglected femoral neck fractures in young
      adults.
AB  - Twenty cases of neglected (more than 1 month old) displaced femoral neck
      fractures in young adults were treated with a valgus intertrochanteric osteotomy.
      A fracture union rate of 85% (17 cases) was achieved. Two of the healed cases
      developed avascular necrosis. After 30 months 15 patients (75%) had achieved good
      to excellent results. We believe that intertrochanteric osteotomy provides good
      alternative management for neglected femoral neck fractures.

PMID- 11820443
TI  - Femoral nailing with transverse locking screws through the femoral neck.
AB  - We treated 55 patients with subtrochanteric or comminuted femoral fractures with
      a transverse locking femoral nail (Alta, Howmedica). This nail was positioned
      more cephalad than usual so that at least one fixation screw was located in the
      femoral neck or head. Forty-seven fractures (20 subtrochanteric and 27
      diaphyseal) were available for follow-up averaging 12 months (3-35). The time to
      radiographic healing averaged 7 months (3-21). There was one delayed union, one
      non-union, two superficial infections, one broken proximal screw, one compartment
      syndrome of the thigh, and one peroneal nerve palsy. There were no femoral neck
      fractures, avascular changes of the femoral head, or gluteal irritation at the
      most recent follow up. The described technique appears safe and effective, is
      technically easy, and avoids intra-articular screws.

PMID- 11820444
TI  - Preoperative, single-fraction irradiation for prophylaxis of heterotopic
      ossification after total hip arthroplasty.
AB  - We gave a single fraction of 750 cGy preoperatively (within 16 h of surgery) to
      143 patients prior to total hip arthroplasty. The patients were evaluated for
      heterotopic ossification at 1, 3 and 6 months. The preoperative radiation did not
      affect the surgical procedure. After a median follow-up of 12 (6-24) months we
      encountered six patients with heterotopic ossifications of Brooker grade I-II.
      Potential late risks from ionising radiation should be considered when treating
      younger patients.

PMID- 11820445
TI  - Modular megaprosthesis for distal femoral tumors.
AB  - We treated 48 patients with distal femoral tumors by resection and limb salvage
      with an uncemented megaprosthesis (Howmedica Modular Replacement System).
      Diagnoses included: 32 osteosarcomas, five chondrosarcomas, six giant cell tumors
      of the bone, three fibrosarcomas, and two Ewing's sarcomas. The mean follow-up
      was 5.6 years (2-10 years). The overall complication rate was 39%. Seven patients
      died of their disease, but none from complications related to the surgery. Five
      patients were revised to arthrodesis, and one required amputation because of
      complications. The mean postoperative Musculoskeletal Tumor Society score (MSTS)
      score was 21 (6-28) for the remaining 35 patients. The most frequent
      complications were infection (14.6%) and aseptic loosening (4.8%). Ten-year
      survival of the prosthesis was 65%.

PMID- 11820446
TI  - Miller-Galante total knee arthroplasty: the importance of material and design on
      the revision rate.
AB  - We have reviewed 142 Miller-Galante I (MG I) total knee arthroplasties (TKAs)
      with a follow-up of 56 months, and compared these with the outcome of 219 Miller
      Galante II (MG II) TKAs with a follow-up of 36 months. In the MG II TKAs we found
      markedly lower revision rates, higher postoperative Hospital for Special Surgery
      (HSS) scores, less retropatellar pain and better patellar centring without
      patellar resurfacing. The higher revision rate in MG I TKAs was mainly due to the
      need to revise the metal-backed patellae.

PMID- 11820447
TI  - Surgery for hallux valgus. The expectations of patients and surgeons.
AB  - Two-hundred patients who had undergone surgery for hallux valgus were interviewed
      in an attempt to study the different variables which may have contributed to the
      success of their surgery. These data were compared to the results obtained by
      using clinically applied scores. To obtain data on surgeons' expectations, 186
      members of two national orthopaedic foot societies were interviewed in order to
      quantify the importance and value of these variables in prognosis. The main
      interest of the patients is a painless great toe which, when wearing conventional
      shoes, gives no problems. They also wish to have their bursitis and bunion
      treated in order to regain their ability to walk as much as they wish. Surgeons
      are not only specially interested in pain and shoe problems but also in restoring
      an adequate range of motion in the metatarsophalangeal joint (MTP), removal of
      the bunion and the treatment of tender callosities. We found that the correction
      of footwear problems, alleviation of pain and restoration of adequate walking are
      the most important factors influencing the outcome of surgery. It was surprising
      that these expectations are only partly revealed by using clinical foot scores.

PMID- 11820448
TI  - Open fractures of the lower limb in Nigeria.
AB  - During an 18-month period we studied prospectively 63 consecutive patients (42
      males, 21 females) with an open fracture of the lower limb. Their mean age was 32
      years (range: 4-78 years) and 58 patients with 59 fractures were available until
      the conclusion of the study. Forty-seven had tibial fractures, 12 had femoral
      fractures and the majority of the patients were either students or traders.
      According to Gustilo and Anderson's grading, 21 fractures were of type II and 16
      of type IIIA. On arrival all the wounds were irrigated and debrided and the
      patients also received tetanus prophylaxis and intravenous antibiotics. Of the 47
      tibial fractures 39 were managed with an above-knee plaster of Paris cast which
      was windowed so as to allow wound care. Of the 12 femoral fractures ten were
      treated with skeletal traction on a Bohler frame. The time taken for soft tissue
      healing was not significantly different between the tibial and femoral fractures.
      There were, however, significant differences with respect to (1) the time
      interval between injury and debridement, (2) the incidence of wound infection,
      (3) the occurrence of osteomyelitis, (4) fracture union time, and (5) time spent
      in hospital. The most common complications were wound infections (27 cases) and
      delayed union (26 cases). The time interval between injury and wound debridement
      was a major prognostic factor.

PMID- 11820449
TI  - Squamous cell carcinoma arising in chronic osteomyelitis.
AB  - Squamous cell carcinoma (SCC) is a rare but well-documented complication of
      chronic osteomyelitis. Between February 1991 and March 1999, 13 cases (12 men and
      one woman) of SCC arising in chronic osteomyelitis were diagnosed and treated in
      our clinic. Mean age was 56.5 (38-70) years. Twelve patients underwent amputation
      and one underwent limb salvage. Average follow-up was 56 (24-121) months. Among
      the 13 patients two died of the disease. Treatment of choice for these tumours
      has been amputation.

PMID- 11820450
TI  - Peripheral tears of triangular fibrocartilage complex: results of primary repair.
AB  - In 16 patients with ulnar wrist pain, we performed primary arthroscopic or open
      repair of the peripheral rim tears of the triangular fibrocartilage complex
      (TFCC) (14 ulnar, 4 volar, and 3 radial tears). The wrist function was assessed
      before and 1 year after the repair using the Mayo-modified wrist score. The
      average pain score improved from 9.1+/-8.0 to 21.2+/-6.5, the average functional
      score from 5.0+/-8.1 to 20.6+/-6.3, the average motion score from 4.7+/-2.8 to
      15.6+/-7.3, and the average grip point from 4.4+/-3.5 to 15.6+/-7.7, all with
      significant differences (P<0.01). Ten of the 17 cases had instability of the
      distal radioulnar joint and five had recurrent instability after repair.

PMID- 11820451
TI  - Treatment of humeral shaft non-unions by the Ilizarov method.
AB  - Thirty-five humeral shaft non-unions treated by the Ilizarov external fixator
      were studied after an average of 39 months. Bone union was achieved in all but
      one. The mean time to union was 5.5 months (range: 3-10 months). Major pin tract
      problems leading to removal of the Schanz screws occurred in three patients. A
      radial nerve palsy developed in three patients, two recovered spontaneously and
      one was treated with a triple tendon transfer.

PMID- 11820453
TI  - Transient bone marrow edema of the foot.

PMID- 11820452
TI  - Chondrolysis of the glenohumeral joint following a color test using gentian
      violet.
AB  - Two patients developed chondrolysis following injection of 0.4% aqueous gentian
      violet into the glenohumeral joint to visualize a rotator cuff tear during
      surgery. In both cases, conventional radiographs revealed joint space narrowing
      10-12 months after surgery. Histological examination of the humeral heads
      revealed loss of the articular cartilage.

PMID- 11820454
TI  - Hyperalgesia and edema responses induced by rat peripheral blood mononuclear
      cells incubated with carrageenin.
AB  - The aim of this study was to verify the role played by mononuclear cells in an
      acute (nonimmune) inflammatory reaction. Mononuclear cells purified from rat
      peripheral blood were incubated for 1, 2, or 24 h with 100 or 250 microg/ml
      carrageenin (Cg). The resultant donor supernatant was injected into recipient
      rats to test its ability to induce hyperalgesia (reduction in threshold for paw
      pressure) and edema (increase in paw volume). Mononuclear cell supernatants (MnS)
      induced a significant time- and dose-dependent hyperalgesia and edema in rat
      paws, which reached a maximal effect at 3 h, lasted for 6 h, and returned to
      basal levels at 24 h of injection. Prostaglandins and cytokines (interleukin 1,
      2, 6, 8, and tumor necrosis factor alpha) accounted for the hyperalgesia induced
      by MnS, as it was reduced (40 to 90%) by synthesis inhibitors such as
      indomethacin, dexamethasone, rolipram, and cyclosporin added to the cultures at a
      microgram dose-range. Edema was dependent on serotonin release in rat paws. These
      results indicate that mononuclear cells may be important contributors to acute
      inflammatory reactions, especially under those conditions where pain is an
      important component.

PMID- 11820455
TI  - Release of TNF-alpha from lipopolysaccharide (LPS)-stimulated Kupffer cells in
      serum- and nutrient-free medium.
AB  - In monocytes/macrophages LPS stimulation occurs by the binding of LPS and the
      serum component LPS-binding protein (LBP) to CD14. This study was conducted to
      investigate whether this mechanism also occurs in Kupffer cells. Rat Kupffer
      cells were stimulated for up to 8 h by LPS (0, 100 ng/ml, 10 microg/ml) in RPMI
      medium or in nutrient-free Krebs-Henseleit (KH) buffer. Some incubations were
      performed without serum, while in others serum was provided. TNF-alpha
      concentrations of the supernatants were measured by ELISA. LPS stimulation of
      Kupffer cells yielded the following results. In KH without any additives a
      considerable amount of TNF-alpha was released. Incubation in RPMI without serum
      caused twice as much TNF-alpha to be released as when KH was used. The addition
      of autologous serum to RPMI did not increase TNF-alpha response. These results
      provide evidence that a substantial part of TNF-alpha release by LPS-stimulated
      Kupffer cells occurs in a serum- and thus LBP-independent way.

PMID- 11820456
TI  - Cloning and relative expression analysis of rat stromal cell derived factor-1
      (SDF-1)1: SDF-1 alpha mRNA is selectively induced in rat model of myocardial
      infarction.
AB  - Stromal cell derived factor-1 (SDF-1) is a member of the non-ELR subfamily of CXC
      chemokines. SDF-1 and its receptor, CXCR4, are essential for cardiogenesis,
      hematopoiesis, and vasculogenesis during embryonic development, in addition to
      involvement in chemotaxis of leukocyte subsets and endothelial cells. In order to
      study SDF-1 expression in a rat model of myocardial infarction, we cloned and
      functionally expressed the rat SDF-1alpha orthologue. Rat SDF-1alpha is highly
      conserved, with >95% identity to its known human, feline, and murine
      counterparts. Constitutive expression of SDF-1 mRNA was observed in heart, brain,
      liver, and kidney. Significantly, apart from the SDF-1alpha and beta splice
      variants, expression of the recently identified SDF-1gamma was uniquely abundant
      in the heart. SDF-1alpha mRNA was selectively induced in permanent coronary
      artery occlusion model of myocardial infarction in rat, while SDF-1gamma remained
      unchanged. Such modulation of SDF-1alpha mRNA expression may be indicative of its
      role in the inflammatory events in cardiovascular disease.

PMID- 11820457
TI  - Effects of a COX-2 preferential agent nimesulide on TNBS-induced acute
      inflammation in the gut.
AB  - In inflammatory bowel disease, increased production of prostaglandins by
      cyclooxygenase-2 (COX-2) contributes to bowel dysfunction, inflammatory edema,
      and hyperemia suggesting that inhibitors of COX-2 may have beneficial effect in
      gut inflammation. We compared the effects of nimesulide, a preferential COX-2
      inhibitor, with those of indomethacin, acetylsalicylic acid (ASA), and
      dexamethasone in a 24-h model of 2,4,6-trinitrobenzenesulfonic acid (TNBS)
      induced colitis in the rat. TNBS-induced colitis was associated with enhanced COX
      2 expression in the gut and increased circulating concentrations of PGE2
      metabolite (PGEM). Treatment with nimesulide (10 mg/kg), indomethacin (10 mg/kg),
      or dexamethasone (1 mg/kg) reduced plasma PGEM concentrations and edema in the
      inflamed bowel. In addition, nimesulide and dexamethasone treatments decreased
      neutrophil infiltration into the inflamed colon mucosa. ASA (10 mg/kg) did not
      have a significant effect on any of these measures of inflammation. None of the
      studied drugs reduced the size of inflammatory mucosal lesions in the colon. In
      TNBS-induced acute inflammation of the colon, nimesulide reduced the formation of
      inflammatory edema, probably by a mechanism related to inhibition of PGE2
      production by COX-2 pathway. In addition, nimesulide inhibited neutrophil
      infiltration into inflamed mucosa mimicking the action of dexamethasone.

PMID- 11820458
TI  - Beneficial effects of glycocholic acid (GCA) on gut mucosal damage in bile duct
      ligated rats.
AB  - In order to investigate the effect of bile acids on gastrointestinal
      inflammations, bile duct ligated rats (BDL) were treated with GCA (25 mM/ml, oral
      or colonic) or saline I h before ethanol challenge and twice daily for 3 days in
      the ileitis group, while GCA was given twice daily for 3 days in the colitis
      group. BDL reduced the macroscopic and microscopic damage scores in the ileitis
      group compared to sham operated group, while it had no significant effect on
      ulcer or colitis groups. However, GCA given in BDL group reduced the ulcer index
      and microscopic damage in colitis group compared to saline-treated groups, but
      had no effect in ileitis group. Both BDL and GCA administration in BDL group
      reduced ileitis- or colitis-induced elevations in MPO levels. GCA administration
      in BDL group inhibited gastric acid output and volume. Our results suggest that
      oral or colonic administration of primary bile acids may be useful for the
      treatment of gastrointestinal inflammations.

PMID- 11820459
TI  - Interaction of amorphous calcium phosphate with fibrin in vitro causes decreased
      fibrinolysis and altered protease profiles: implications for atherosclerotic
      disease.
AB  - Previously, we demonstrated that amorphous calcium phosphate (ACP), chemical
      precursor to apatite, strongly interacted with fibrin and facilitated binding of
      matrix metalloproteinase (MMP)-9, a type IV collagenase. Plasmin-dependent
      fibrinolysis resulted in coordinate MMP-9 activation. Here we report on the
      effect(s) of ACP on fibrin degradation and binding of endogenous plasma
      proteases. Electrophoresis (8.5% SDS-PAGE) revealed that fibrin formed in the
      presence of ACP demonstrated characteristic gamma-gamma dimers (90-kDa) and beta
      monomers (55-kDa), but resisted spontaneous fibrinolysis (72 h, 37 degrees C) or
      degradation by plasminogen activators (uPA, tPA). Casein zymography revealed an
      ACP-dependent decrease in fibrin binding of a low molecular weight (Mw) protease
      triplet (47-, 43-, 42-kDa) and increased fibrin binding of two high Mw proteases
      (94- and 84-kDa). The low Mw triplet also possessed gelatinolytic activity, but
      was not an MMP since 1,10-phenanthroline was ineffective as an inhibitor. Fibrin
      binding proteases were inhibited to some degree by the serine protease inhibitor
      aprotinin. Competition/dissociation experiments with epsilon-aminocaproic acid
      revealed that the low Mw triplet lacked kringle regions whereas the 94- and 84
      kDa proteases were tentatively identified and glu-/lys-plasmin(ogen)s. The
      triplet may, however, represent one or more kringle deficient mini
      plasminogen(s), since electrophoretic mobility and substrate specificity was
      similar to elastase-generated mini-plasminogen. To explore these findings in a
      clinically relevant setting, a series of plasma samples was collected from a
      patient with unstable angina prior to, during, and post coronary artery bypass
      graft (CABG) surgery. Fibrin formed from plasma collected during and immediately
      post CABG was associated with increased fibrinolytic capacity and enhanced
      binding of a) MMP-9, b) the low Mw protease triplet (described above), and c) PA
      (as putative 110-kDa tPA:PAI-1 complex). The relevance of these findings to
      pathologic calcification of atherosclerotic plaques is discussed.

PMID- 11820460
TI  - Influence of low molecular weight heparin (certoparin) and unfractionated heparin
      on the release of cytokines from human leukocytes.
AB  - We analyzed the influence of heparins (unfractionated heparin, UFH and low
      molecular weight heparin certoparin) on the generation of IL-1ra, IL-6, IL-10,
      and IL-12p40 and from leukocyte fractions in vitro. Polymorphonuclear neutrophil
      leukocytes (PMN) and peripheral blood mononuclear cells (PBMC) from 16 different
      healthy donors were isolated and adjusted to 1 x 10(6) cells/ml supplemented RPMI
      1640. Leukocyte fractions were differentially stimulated (PMN with 1 microg and 5
      microg LPS, PBMC with 10 ng TSST- 1 or 2 microg ConA) in the presence or absence
      of heparins (1 U/ml, 2 U/ml, and 4 U/ml) for 24 h at 37 degrees C. Cytokine
      release was analyzed by ELISA. Certoparin but not UFH led to a dose-dependent
      increase in IL-6 from non-stimulated PBMC. In contrast, the release of IL-1ra, IL
      10, and IL-12p40 was not modulated by heparins in a dose-dependent fashion.
      Increases in these cytokines occurred only as single incidents at intermediate
      heparin levels. An influence of the heparins on the apoptosis of PMN (measured as
      DNA-fragmentation in non-stimulated or LPS-stimulated cell-fractions) was not
      observed.

PMID- 11820461
TI  - Thermal injury increases the number of eosinophil progenitors in rat spleen and
      bone marrow.
AB  - We have investigated the effects of thermal injury upon myelopoiesis. IL-3, GM
      CSF, and IL-5 were used to stimulate myeloid colony formation. IL-3 induces early
      myeloid progenitors and a more developed myeloid progenitor, the granulocyte
      macrophage colony-forming unit (GM-CFU), to multiply and develop into mature
      myeloid cells. GM-CSF induces GM-CFU to become mature myeloid cells, while IL-5
      induces eosinophil progenitors to become mature eosinophils. Stem Cell Factor
      (SCF) + IL-6 and FLT3 ligand, which have no effect on colony formation by
      themselves, were used to enhance the effects of IL-3 and GM-CSF, respectively. We
      found that thermal injury increased the number of early myeloid progenitors and
      GM-CFU in the spleen with either IL-3 or GM-CSF as a stimulant. Thermal injury
      increased the number of early myeloid progenitors in the bone marrow when GM-CSF,
      but not IL-3, was used to stimulate colony growth. Also, thermal injury increased
      the numbers of eosinophil progenitors in rat spleen and bone marrow and increased
      splenic levels of IL-5 mRNA.

PMID- 11820462
TI  - The Dutch Deep Hyperthermia Trial: results in cervical cancer.
AB  - BACKGROUND: Radiotherapy plus hyperthermia was compared to radiotherapy alone in
      the Dutch Deep Hyperthermia Trial, in patients with advanced bladder, cervical,
      and rectal tumours. The overall results, published elsewhere, demonstrate that
      addition of hyperthermia to radiotherapy improves both pelvic control and overall
      survival rates. The therapeutic gain appeared especially worthwhile in locally
      advanced cervical tumours. Here, the results in patients with cervical cancer are
      summarized and discussed, and further details provided. METHODS: From 1990-1996,
      114 patients with cervical cancer were entered into this prospective randomized
      trial. RT was applied to a median total dose of 68 Gy. HT was given once weekly.
      The median follow-up time was 43 months. All randomized patients were included in
      the statistical analysis, which was done by intention to treat. The primary end
      points of the trial were complete response (CR) and duration of pelvic control
      (PC), secondary end points were overall survival (OS) and toxicity. Besides, an
      economic evaluation was performed. RESULTS: CR rates were 57% following RT and
      83% following RT + HT(p = 0.003). The difference in PC was maintained during
      follow-up, with 3-year LC rates of 41% following RT and 61% following RT + HT.
      The 3-year OS rates were 27% and 51% following RT and RT + HT, respectively (p =
      0.009). When the patients were divided into two subgroups by whether or not the
      planned RT was completed, a beneficial effect of hyperthermia was observed in
      both subgroups. Radiation toxicity was not enhanced by HT. Additional
      hyperthermia proved to be cost-effective, with maximum discounted cost-per-life
      year gained of about Euro 4000. CONCLUSION: Hyperthermia in addition to standard
      radiotherapy of locally advanced cervical tumours results in therapeutic gain and
      is cost-effective.

PMID- 11820463
TI  - Counterpoint: test the value of hyperthermia in patients with carcinoma of the
      cervix being treated with concurrent chemotherapy and radiation.
AB  - Major advances in the treatment of locally advanced cervical carcinoma were
      reported in 1999-2000 in five studies from the Gynecologic Oncology Group,
      Radiation Therapy Oncology Group and Southwestern Oncology Group. Collectively
      these trials reported a decrease in the risk of recurrence or death from cervical
      cancer ranging from 30-50% with the use of concurrent chemoradiation, as compared
      with radiation alone. On the basis of these trials the National Cancer Institute
      in 1999 issued a clinical alert concluding 'Strong consideration should be given
      to the incorporation of concurrent cisplatin-based chemotherapy with radiation
      therapy in women who require radiation therapy for treatment of cervical cancer.'
      Concurrently with these publications there appeared the publication in the Lancet
      in 2000 of the Dutch Deep Hyperthermia Group trial of radiotherapy alone versus
      combined radiation and hyperthermia for locally advanced pelvic tumors including
      carcinoma of the cervix. This multi-center phase III trial demonstrated an
      approximate doubling of the three year survival from 27 to 51% for the addition
      of hyperthermia to radiotherapy in patients with locally advanced cervical
      carcinoma. Additional trials to test the value of hyperthermia in patients with
      cervical carcinoma treated with concurrent chemotherapy and radiation are
      imperative and take precedence over a trial to investigate the value of
      chemotherapy in patients treated with hyperthermia and radiation.

PMID- 11820465
TI  - A new phase III trial for treatment of carcinoma of the cervix.

PMID- 11820464
TI  - Referee: hyperthermia alone or combined with cisplatin in addition to
      radiotherapy for advanced uterine cervical cancer.
AB  - There are two evidence based therapeutic options for locally advanced cervical
      cancer: Radiotherapy and concurrent chemotherapy (cisplatin alone or combined
      with other drugs) or radiation and hyperthermia, documented in randomised trials.
      The weight of evidence is less for the most advanced stages. Combination of all
      three options are currently tested in several centres with good clinical response
      and acceptable toxicity. Based on a pragmatic approach we propose to proceed with
      a trial selecting cisplatin concurrent with radiation therapy as the standard arm
      to be compared with the same regimen with the addition of hyperthermia once a
      week.

PMID- 11820466
TI  - Comparison of response to radiation, hyperthermia and cisplatin in parental and
      polymerase beta knockout cells.
AB  - The role of polymerase beta in response to radiation, cisplatin and hyperthermia
      was examined in a pair of mouse cell lines, comprising a normal parental line and
      a derivative with polymerase beta knockout. Cell survival was assessed using the
      colony survival assay. For irradiation, there was no difference in response
      between the two cell lines. Treatment with cisplatin for 1 h showed a large
      increase in resistance in the mutant cell line. The results with hyperthermia
      were more complex. The mutant was more resistant to 45 degrees C heating, but was
      slightly more heat sensitive than the wild type at 41 degrees C. Thus, in
      summary, while the knockout of polymerase beta did not alter radiation
      sensitivity, it did increase resistance to cisplatin and induced resistance to
      hyperthermia at higher temperatures (45 degrees C).

PMID- 11820467
TI  - Some general regularities of synergistic interaction of hyperthermia with various
      physical and chemical inactivating agents.
AB  - Various cellular systems have been analysed for synergistic interactions of the
      simultaneous action of hyperthermia with physical agents including ionizing
      radiation, ultraviolet light, and ultrasound, and with chemical agents including
      thio-TEPA and cis-DDP. Some general rules of synergistic interaction were
      revealed. First, for every constant rate or intensity of exposure to physical
      factors or concentration of chemical agents, synergy can be observed only within
      a certain temperature range that is different for various cellular systems.
      Secondly, within this range, there is a specific temperature that maximizes the
      synergistic effect. Any deviation of temperature from the optimal one results in
      a reduction in synergy. Thirdly, the rate of exposure to physical agents or the
      concentration of chemical agents strongly influences the synergy; i.e. as the
      dose rate or concentration is reduced, the temperature for maximum synergism
      decreases. Possible interpretations of the mechanisms responsible for these
      relationships of synergy are discussed.

PMID- 11820468
TI  - In vitro thermo- and thermochemo-sensitivity of retinoblastoma cells from
      surgical specimens.
AB  - The sensitivity to heat and chemical modification of human retinoblastoma cells
      obtained from patients with primary retinoblastoma was studied in vitro by the
      human tumour colony assay established by Hamburger and Salmon in 1977.
      Retinoblastoma cells showed moderate sensitivity to 1 h of hyperthermia at 42
      degrees C; the median T/C% (ratio of the colony number in treated vs. control
      dishes, x 100) under hyperthermia was 47.0% for 46 tumours studied. When tumours
      were treated with melphalan, cis-diamminedichloroplatinum (II), adriamycin,
      etoposide and teniposide at 37 degrees C and 42 degrees C, the median T/C% for
      each chemical agent was decreased significantly by concomitant hyperthermia. One
      hour exposure of 38 tumours to melphalan, cis-diamminedichloroplatinum (II) (30
      tumours), adriamycin (27 tumours), teniposide (22 tumours) and etoposide (20
      tumours) at 37 degrees C gave median T/C%s of 9.5, 33.5, 16.0, 3.8 and 38.0%,
      respectively, while exposure at 42 degrees C gave values of 2.4, 8.2, 5.6, 1.0
      and 6.6%, respectively. Combination of heat and chemical treatment with
      melphalan, cis-diamminedichloroplatinum (II) and etoposide appeared to be
      synergistic with median T/C%s that were significantly lower than the median T/C%s
      expected from a simple sum of their individual effects. These in vitro results
      suggest that combining the treatment modalities of hyperthermia and chemotherapy
      for primary retinoblastoma would be advantageous.

PMID- 11820469
TI  - Cell killing of melanoma B16 in vivo by hyperthermia and cytotoxins.
AB  - The aim of this study was to investigate antitumour activity of cisplatin,
      dacarbasine, cyclophosphamide and a new compound from the nitrosourea group-
      acetamido-CNU ((2-chloroethyl)-1-nitroso-3-(methylenecarboxamido)-urea)--applied
      with or without local hyperthermia (43.5 degrees C/60 min). The tumour model for
      the investigation of antitumour activity was a mouse melanoma B16 transplanted
      into the footpad. Dacarbasine, cyclophosphamide and acetamido-CNU applied as a
      single treatment had statistically significant antitumour activity, while
      cisplatin applied as a single agent had no effect. Local hyperthermia alone had
      statistically significant antitumour activity. The best therapeutic effect
      (synergistic) was obtained when combined treatment (cytotoxins plus local
      hyperthermia) was used. Synergistic therapeutic results were achieved even when
      cisplatin and hyperthermia were combined, although cisplatin was ineffective when
      given as a single agent. Therapeutic results achieved with acetamido-CNU (newly
      synthesized compound) applied alone were similar to the therapeutic results
      achieved with dacarbasine or cyclophosphamide. In combined therapy (acetamido-CNU
      + HT), achieved therapeutic results were significantly better (p < 0.05) than
      results achieved by combining cisplatin and hyperthermia or dacarbasine and
      hyperthermia.

PMID- 11820470
TI  - Biogeochemical characterisation of a coal tar distillate plume.
AB  - The distillation of acidified coal tars for up to 50 years has given rise to a
      phenol plume approximately 500 m long, 50 m deep and containing up to 15 g l(-1)
      dissolved organic carbon (DOC) in the Triassic Sandstones aquifer. A conceptual
      biogeochemical model based on chemical and microbiological analysis of
      groundwater samples has been developed as a preliminary to more detailed studies
      of the controls on natural attenuation. While the development of redox zones and
      the production of methane and carbon dioxide provide evidence of natural
      attenuation, it appears that degradation is slow. The existence of sulphate in
      the plume indicates that this electron acceptor has not been depleted and that
      consequently methanogenesis is probably limited. Based on a simple estimate of
      sulphate input concentration, a half-life of about 15 years has been estimated
      for sulphate reduction. Geochemical modelling predicts that increased alkalinity
      within the plume has not led to carbonate precipitation, and thus within the
      limits of accuracy of the measurement, alkalinity may reflect the degree of
      biodegradation. This implies a loss of around 18% of the DOC over a 30-year
      period. Despite limited degradation, microbial studies show that there are
      diverse microbial communities in the aquifer with the potential for both
      anaerobic and aerobic biodegradation. Microbial activity was found to be greatest
      at the leading edge of the plume where DOC concentrations are 60 mg l(-1) or
      less, but activity could still be observed in more contaminated samples even
      though cells could not be cultured. The study suggests that degradation may be
      limited by the high phenol concentrations within the core of the plume, but that
      once diluted by dispersion, natural attenuation may proceed. More detailed
      studies to confirm these initial findings are identified and form the basis of
      associated papers.

PMID- 11820471
TI  - Assessing the natural attenuation of organic contaminants in aquifers using plume
      scale electron and carbon balances: model development with analysis of
      uncertainty and parameter sensitivity.
AB  - A quantitative methodology is described for the field-scale performance
      assessment of natural attenuation using plume-scale electron and carbon balances.
      This provides a practical framework for the calculation of global mass balances
      for contaminant plumes, using mass inputs from the plume source, background
      groundwater and plume residuals in a simplified box model. Biodegradation
      processes and reactions included in the analysis are identified from electron
      acceptors, electron donors and degradation products present in these inputs.
      Parameter values used in the model are obtained from data acquired during typical
      site investigation and groundwater monitoring studies for natural attenuation
      schemes. The approach is evaluated for a UK Permo-Triassic Sandstone aquifer
      contaminated with a plume of phenolic compounds. Uncertainty in the model
      predictions and sensitivity to parameter values was assessed by probabilistic
      modelling using Monte Carlo methods. Sensitivity analyses were compared for
      different input parameter probability distributions and a base case using fixed
      parameter values, using an identical conceptual model and data set. Results show
      that consumption of oxidants by biodegradation is approximately balanced by the
      production of CH4 and total dissolved inorganic carbon (TDIC) which is conserved
      in the plume. Under this condition, either the plume electron or carbon balance
      can be used to determine contaminant mass loss, which is equivalent to only 4% of
      the estimated source term. This corresponds to a first order, plume-averaged,
      half-life of > 800 years. The electron balance is particularly sensitive to
      uncertainty in the source term and dispersive inputs. Reliable historical
      information on contaminant spillages and detailed site investigation are
      necessary to accurately characterise the source term. The dispersive influx is
      sensitive to variability in the plume mixing zone width. Consumption of aqueous
      oxidants greatly exceeds that of mineral oxidants in the plume, but electron
      acceptor supply is insufficient to meet the electron donor demand and the plume
      will grow. The aquifer potential for degradation of these contaminants is limited
      by high contaminant concentrations and the supply of bioavailable electron
      acceptors. Natural attenuation will increase only after increased transport and
      dilution.

PMID- 11820472
TI  - Processes controlling the distribution and natural attenuation of dissolved
      phenolic compounds in a deep sandstone aquifer.
AB  - Processes controlling the distribution and natural attenuation (NA) of phenol,
      cresols and xylenols released from a former coal-tar distillation plant in a deep
      Triassic sandstone aquifer are evaluated from vertical profiles along the plume
      centerline at 130 and 350 m from the site. Up to four groups of contaminants
      (phenols, mineral acids, NaOH, NaCl) form discrete and overlapping plumes in the
      aquifer. Their distribution reflects changing source history with releases of
      contaminants from different locations. Organic contaminant distribution in the
      aquifer is determined more by site source history than degradation. Contaminant
      degradation at total organic carbon (TOC) concentrations up to 6500 mg l(-1)
      (7500 mg l(-1) total phenolics) is occurring by aerobic respiration NO3
      reduction, Mn(IV)-/Fe(III)-reduction, SO4-reduction, methanogenesis and
      fermentation, with the accumulation of inorganic carbon, organic metabolites (4
      hydroxybenzaldehyde, 4-hydroxybenzoic acid), acetate, Mn(II), Fe(II), S(-II), CH4
      and H2 in the plume. Aerobic and NO3-reducing processes are restricted to a 2-m
      thick plume fringe but Mn(IV)-/Fe(II)-reduction, SO4-reduction, methanogenesis
      and fermentation occur concomitantly in the plume. Dissolved H2 concentrations in
      the plume vary from 0.7 to 110 nM and acetate concentrations reach 200 mg l(-1).
      The occurrence of a mixed redox system and concomitant terminal electron
      accepting processes (TEAPs) could be explained with a partial equilibrium model
      based on the potential in situ free energy (deltaGr) yield for oxidation of H2 by
      specific TEAPs. Respiratory processes rather than fermentation are rate limiting
      in determining the distribution of H2 and TEAPs and H2 dynamics in this system.
      Most (min. 90%) contaminant degradation has occurred by aerobic and NO3-reducing
      processes at the plume fringe. This potential is determined by the supply of
      aqueous O2 and NO3 from uncontaminated groundwater, as controlled by transverse
      mixing, which is limited in this aquifer by low dispersion. Consumption to date
      of mineral oxides and SO4 is, respectively, <0.15% and 0.4% of the available
      aquifer capacity, and degradation using these oxidants is <10%. Fermentation is a
      significant process in contaminant turnover, accounting for 21% of degradation
      products present in the plume, and indicating that microbial respiration rates
      are slow in comparison with fermentation. Under present conditions, the potential
      for degradation in the plume is very low due to inhibitory effects of the
      contaminant matrix. Degradation products correspond to <22% mass loss over the
      life of the plume, providing a first-order plume scale half-life >140 years. The
      phenolic compounds are biodegradable under the range of redox conditions in the
      aquifer and the aquifer is not oxidant limited, but the plume is likely to be
      long-lived and to expand. Degradation is likely to increase only after
      contaminant concentrations are reduced and aqueous oxidant inputs are increased
      by dispersion of the plume. The results imply that transport processes may exert
      a greater control on the natural attenuation of this plume than aquifer oxidant
      availability.

PMID- 11820473
TI  - Microbiological analysis of multi-level borehole samples from a contaminated
      groundwater system.
AB  - A range of bacteriological, geochemical process-related and molecular techniques
      have been used to assess the microbial biodegradative potential in groundwater
      contaminated with phenol and other tar acids. The contaminant plume has travelled
      500 m from the pollutant source over several decades. Samples were obtained from
      the plume using a multi-level sampler (MLS) positioned in two boreholes
      (boreholes 59 and 60) which vertically transected two areas of the plume.
      Activity of the microbial community, as represented by phenol degradation
      potential and ability to utilise a range of substrates, was found to be
      influenced by the plume. Phenol degradation potential appeared to be influenced
      more by the concentration of the contaminants than the total bacterial cell
      numbers. However, in the areas of highest phenol concentration, the depression of
      cell numbers clearly had an effect. The types of bacteria present were assessed
      by culture and DNA amplification by polymerase chain reaction (PCR). Bacterial
      groups or processes associated with major geochemical processes, such as
      methanogenesis, sulphate reduction and denitrification, that have the potential
      to drive contaminant degradation, were detected at various borehole levels. A
      comparative molecular analysis of the microbial community between samples
      obtained from the MLS revealed the microbial community was diverse. The
      examination of microbial activity complemented those results obtained through
      chemical analysis, and when combined with hydrological data, showed that MLS
      samples provided a realistic profile of plume effects and could be related to the
      potential for natural attenuation of the site.

PMID- 11820474
TI  - Isotopic modelling of the significance of bacterial sulphate reduction for phenol
      attenuation in a contaminated aquifer.
AB  - A Triassic sandstone aquifer polluted with a mixture of phenolic hydrocarbons has
      been investigated by means of high-resolution groundwater sampling. Samples taken
      at depth intervals of 1 m have revealed the presence of a diving pollutant plume
      with a sharply defined upper margin. Concentrations of pollutant phenols exceed 4
      g/l in the plume core, rendering it sterile but towards the diluted upper margin
      evidence for bacterial sulphate reduction (BSR) has been obtained. Groundwaters
      have been analysed for both delta34S-SO4 and delta18O-SO4. Two reservoirs have
      been identified with distinct sulphate oxygen isotope ratios. Groundwater
      sulphate (delta18O-SO4 = 3-5/1000) outside the plume shows a simple linear mixing
      trend with an isotopically uniform pollutant sulphate reservoir (delta18O-SO4 =
      10-12/1000) across the plume margin. The sulphur isotope ratios do not always
      obey a simple mixing relation, however, at one multilevel borehole, enrichment in
      34SO4 at the plume margin is inversely correlated with sulphate concentration.
      This and the presence of 34S-depleted dissolved sulphide indicate that enrichment
      in 34SO4 is the result of bacterial sulphate reduction. Delta34S analysis of
      trace hydrogen sulphide within the plume yielded an isotope enrichment factor
      (epsilon) of -9.4/1000 for present-day bacterial sulphate reduction. This value
      agrees with a long-term estimate (-9.9/1000) obtained from a Rayleigh model of
      the sulphate reduction process. The model was also used to obtain an estimate of
      the pre-reduction sulphate concentration profile with depth. The difference
      between this and the present-day profiles then gave a mass balance for sulphate
      consumption. The organic carbon mineralisation that would account for this
      sulphate loss is shown to represent only 0.1/1000 of the phenol concentration in
      this region of the plume. Hence, the contribution of bacterial sulphate reduction
      to biodegradation has thus far been small. The highest total phenolic
      concentration (TPC) at which there is sulphur isotope evidence of bacterial
      sulphate reduction is 2000 mg/l. We suggest that above this concentration, the
      bactericidal properties of phenol render sulphate-reducing bacteria inactive.
      Dissolved sulphate trapped in the concentrated plume core will only be utilised
      by sulphate reducers when toxic phenols in the plume are diluted by dispersion
      during migration.

PMID- 11820475
TI  - Denitrification and phenol degradation in a contaminated aquifer.
AB  - A natural groundwater system modified by pollutant phenols and agricultural
      nitrate has been modelled in the laboratory by a series of sacrificial microcosm
      experiments. Samples of aquifer sediment and groundwater from the margin of the
      phenol plume were used to inoculate anaerobic microcosms enriched in nitrate and
      pollutant phenols. Rapid degradation of phenol and p-cresol was observed over a
      35-day period leading to the generation of inorganic carbon and a number of
      transient intermediates. O-cresol proved to be recalcitrant on the experimental
      time-scale. A mass balance calculation shows that, during degradation, carbon was
      conserved in the aqueous phase. Groundwater-sediment interactions were monitored
      using carbon stable isotope data. A mass balance for solution TIC indicates thatp
      cresol degradation stimulated the dissolution of sedimentary carbonate phases due
      to the formation of carbonic acid. Compound-specific carbon isotope analysis (GC
      IRMS) was used to search for 13C enrichment in residual p-cresol. A slight
      enrichment trend (epsilon = -2.5/1000) was tentatively identified. The potential
      of this fractionation effect for obtaining in situ degradation rates is
      discussed. Results from the microcosm experiments help to explain the observed
      distribution of nitrate and phenols within the polluted aquifer.

PMID- 11820476
TI  - Microcosm studies of microbial degradation in a coal tar distillate plume.
AB  - Investigation of a groundwater plume containing up to 24 g l(-1) phenolic
      compounds suggested that over a period of nearly 50 years, little degradation had
      occurred despite the presence of a microbial community and electron acceptors
      within the core of the plume. In order to study the effect of contaminant
      concentration on degradation behaviour, laboratory microcosm experiments were
      performed under aerobic and anaerobic conditions at four different concentrations
      obtained by diluting contaminated with uncontaminated groundwater. The microcosms
      contained groundwater with total phenols at ca. 200, 250, 660 and 5000 mg l(-1),
      and aquifer sediment that had been acclimatised within the plume for several
      months. The microcosms were operated for a period of 390-400 days along with
      sterile controls to ascertain whether degradation was microbially mediated or
      abiotic. Under aerobic conditions, degradation only occurred at concentrations up
      to 660 mg l(-1) total phenols. At phenol concentrations below 250 mg l(-1) a
      benzoquinone intermediate, thought to originate from the degradation of 2,5
      dimethylphenol, was isolated and identified. This suggested an unusual
      degradative pathway for this compound; its aerobic degradation more commonly
      proceeding via catecholic intermediates. Under anaerobic conditions, degradation
      only occurred in the most dilute microcosm (total phenols 195 mg l(-1)) with a
      loss of p-cresol accompanied by a nonstoichiometric decrease in nitrate and
      sulphate. By inference, iron(III) from the sediment may also have been used as a
      terminal electron acceptor, in which case the amount of biologically available
      iron released was calculated as 1.07 mg Fe(III)/g of sediment. The study shows
      that natural attenuation is likely to be stimulated by dilution of the plume.

PMID- 11820477
TI  - Reactive transport modeling of processes controlling the distribution and natural
      attenuation of phenolic compounds in a deep sandstone aquifer.
AB  - Reactive solute transport modeling was utilized to evaluate the potential for
      natural attenuation of a contaminant plume containing phenolic compounds at a
      chemical producer in the West Midlands, UK. The reactive transport simulations
      consider microbially mediated biodegradation of the phenolic compounds (phenols,
      cresols, and xylenols) by multiple electron acceptors. Inorganic reactions
      including hydrolysis, aqueous complexation, dissolution of primary minerals,
      formation of secondary mineral phases, and ion exchange are considered. One
      dimensional (1D) and three-dimensional (3D) simulations were conducted. Mass
      balance calculations indicate that biodegradation in the saturated zone has
      degraded approximately 1-5% of the organic contaminant plume over a time period
      of 47 years. Simulations indicate that denitrification is the most significant
      degradation process, accounting for approximately 50% of the organic contaminant
      removal, followed by sulfate reduction and fermentation reactions, each
      contributing 15-20%. Aerobic respiration accounts for less than 10% of the
      observed contaminant removal in the saturated zone. Although concentrations of
      Fe(III) and Mn(IV) mineral phases are high in the aquifer sediment, reductive
      dissolution is limited, producing only 5% of the observed mass loss. Mass balance
      calculations suggest that no more than 20-25% of the observed total inorganic
      carbon (TIC) was generated from biodegradation reactions in the saturated zone.
      Simulations indicate that aerobic biodegradation in the unsaturated zone, before
      the contaminant entered the aquifer, may have produced the majority of the TIC
      observed in the plume. Because long-term degradation is limited to processes
      within the saturated zone, use of observed TIC concentrations to predict the
      future natural attenuation may overestimate contaminant degradation by a factor
      of 4-5.

PMID- 11820478
TI  - Progression of natural attenuation processes at a crude-oil spill site: I.
      Geochemical evolution of the plume.
AB  - A 16-year study of a hydrocarbon plume shows that the extent of contaminant
      migration and compound-specific behavior have changed as redox reactions, most
      notably iron reduction, have progressed over time. Concentration changes at a
      small scale, determined from analysis of pore-water samples drained from aquifer
      cores, are compared with concentration changes at the plume scale, determined
      from analysis of water samples from an observation well network. The small-scale
      data show clearly that the hydrocarbon plume is growing slowly as sediment iron
      oxides are depleted. Contaminants, such as ortho-xylene that appeared not to be
      moving downgradient from the oil on the basis of observation well data, are
      migrating in thin layers as the aquifer evolves to methanogenic conditions.
      However, the plume-scale observation well data show that the downgradient extent
      of the Fe2+ and BTEX plume did not change between 1992 and 1995. Instead,
      depletion of the unstable Fe (III) oxides near the subsurface crude-oil source
      has caused the maximum dissolved iron concentration zone within the plume to
      spread at a rate of approximately 3 m/year. The zone of maximum concentrations of
      benzene, toluene, ethylbenzene and xylene (BTEX) has also spread within the
      anoxic plume. In monitoring the remediation of hydrocarbon-contaminated ground
      water by natural attenuation, subtle concentration changes in observation well
      data from the anoxic zone may be diagnostic of depletion of the intrinsic
      electron-accepting capacity of the aquifer. Recognition of these subtle patterns
      may allow early prediction of growth of the hydrocarbon plume.

PMID- 11820479
TI  - Progression of natural attenuation processes at a crude oil spill site: II.
      Controls on spatial distribution of microbial populations.
AB  - A multidisciplinary study of a crude-oil contaminated aquifer shows that the
      distribution of microbial physiologic types is strongly controlled by the aquifer
      properties and crude oil location. The microbial populations of four physiologic
      types were analyzed together with permeability, pore-water chemistry, nonaqueous
      oil content, and extractable sediment iron. Microbial data from three vertical
      profiles through the anaerobic portion of the contaminated aquifer clearly show
      areas that have progressed from iron-reduction to methanogenesis. These locations
      contain lower numbers of iron reducers, and increased numbers of fermenters with
      detectable methanogens. Methanogenic conditions exist both in the area
      contaminated by nonaqueous oil and also below the oil where high hydrocarbon
      concentrations correspond to local increases in aquifer permeability. The results
      indicate that high contaminant flux either from local dissolution or by advective
      transport plays a key role in determining which areas first become methanogenic.
      Other factors besides flux that are important include the sediment Fe(II) content
      and proximity to the water table. In locations near a seasonally oscillating
      water table, methanogenic conditions exist only below the lowest typical water
      table elevation. During 20 years since the oil spill occurred, a laterally
      continuous methanogenic zone has developed along a narrow horizon extending from
      the source area to 50-60 m downgradient. A companion paper [J. Contam. Hydrol.
      53, 369-386] documents how the growth of the methanogenic zone results in
      expansion of the aquifer volume contaminated with the highest concentrations of
      benzene, toluene, ethylbenzene, and xylenes.

PMID- 11820480
TI  - Occurrence and attenuation of specific organic compounds in the groundwater plume
      at a former gasworks site.
AB  - The changing contaminant pattern with travelled distance was investigated in the
      anaerobic groundwater plume downstream from an extended zone containing residual
      NAPL at a former gas manufacturing plant. With increasing distance, O- and N
      heterocyclic aromatic compounds are enriched in the plume relative to the usually
      assessed coal tar constituents (poly- and monocyclic aromatic compounds). In a
      first approximation, the overall concentration decrease of the investigated
      compounds follows a first order overall decay. The half life distance in the
      plume downgradient from the source varied between 20 m for benzene and up to 167
      303 m for alkyl-naphthalenes. Acenaphthene is degraded only within about 50 m
      downstream from the source area, then its concentration remains constant (ca. 180
      microg/l) and far above the legal limit. Dimethyl-benzofurans were the most
      recalcitrant among all compounds which could be quantified with the analytical
      method available. The overall groundwater contamination in the plume is seriously
      underestimated if only BTEX and 16-EPA-PAHs are monitored.

PMID- 11820481
TI  - An analytical quantification of mass fluxes and natural attenuation rate
      constants at a former gasworks site.
AB  - A new integral groundwater investigation approach was used for the first time to
      quantify natural attenuation rates at field scale. In this approach, pumping
      wells positioned along two control planes were operated at distances of 140 and
      280 m downstream of a contaminant source zone at a former gasworks site polluted
      with BTEX- (benzene, toluene, ethyl-benzene, o-, p-xylene) and PAH- (polycyclic
      aromatic hydrocarbons) compounds. Based on the quantified changes in total
      contaminant mass fluxes between the control planes, first-order natural
      attenuation rate constants could be estimated. For BTEX-compounds, these ranged
      from 1.4e-02 to 1.3e-01 day(-1) whereas for PAH-compounds natural attenuation
      rate constants of 3.7e-04 to 3.1e-02 day(-1) were observed. Microbial degradation
      activity at the site was indicated by an increase in dissolved iron mass flux and
      a reduction in sulphate mass flux between the two investigated control planes. In
      addition to information about total contaminant mass fluxes and average
      concentrations, an analysis of the concentration-time series measured at the
      control planes also allowed to semi-quantitatively delineate the aquifer regions
      most likely contaminated by the BTEX- and PAH-compounds.

PMID- 11820482
TI  - Medications and breastfeeding.

PMID- 11820483
TI  - Writing evidence-based clinical reviews.

PMID- 11820484
TI  - Guideline implementation: why don't we do it?

PMID- 11820485
TI  - Obstructive sleep apnea and essential hypertension--is there a link?

PMID- 11820486
TI  - Optimal management of cholesterol levels and the prevention of coronary heart
      disease in women.
AB  - Coronary heart disease, the leading cause of death in women, is largely
      preventable. Lifestyle modifications (e.g., diet and exercise) are the
      cornerstone of primary and secondary prevention. Elevated levels of low-density
      lipoprotein cholesterol and triglycerides and low levels of high-density
      lipoprotein cholesterol are significant risk factors for coronary heart disease.
      Abundant data show inadequate utilization of lipid-lowering therapy in women.
      Even when women are given lipid-lowering agents, target levels often are not
      achieved. Recent guidelines from the American Heart Association and the American
      College of Cardiology encourage a more aggressive approach to lipid lowering in
      women. The National Cholesterol Education Program Adult Treatment Panel III also
      supports this strategy and significantly expands the number of women who qualify
      for intervention.

PMID- 11820487
TI  - Treating obstructive sleep apnea improves essential hypertension and quality of
      life.
AB  - About one half of patients who have essential hypertension have obstructive sleep
      apnea, and about one half of patients who have obstructive sleep apnea have
      essential hypertension. A growing body of evidence suggests that obstructive
      sleep apnea is a major contributing factor in the development of essential
      hypertension. Despite many patients with obstructive sleep apnea having clear
      symptoms of the disorder, an estimated 80 to 90 percent of cases are undiagnosed.
      When physicians routinely seek the diagnosis of obstructive sleep apnea by asking
      patients (especially those with hypertension) three basic sleep-related questions
      about snoring, excessive daytime sleepiness and reports of witnessed apneic
      events, the number of cases diagnosed and treated increases by about eightfold.
      Eliminating snoring and occurrences of apneic-hypopneic episodes will
      dramatically improve patients' quality of sleep and eliminate excessive daytime
      sleepiness, which has a detrimental effect on general functioning. Increased
      alertness will reduce the likelihood that patients will be involved in motor
      vehicle crashes. In most studies in which blood pressure was measured following
      treatment for obstructive sleep apnea, daytime and nighttime blood pressure
      levels were found to decrease significantly. This decrease in blood pressure may
      also reduce the likelihood of cardiovascular complications. The key to the
      diagnosis of obstructive sleep apnea is physician knowledge about the disorder.
      The dramatic improvement in quality of life that occurs when patients are
      successfully treated for obstructive sleep apnea makes detecting and treating
      this disorder imperative.

PMID- 11820488
TI  - Genitourinary infections and their association with preterm labor.
AB  - Genitourinary tract infections are one cause of preterm delivery. Prematurity is
      one of the leading causes of perinatal mortality in the United States. Uterine
      contractions may be induced by cytokines and prostaglandins, which are released
      by microorganisms. Asymptomatic bacteriuria, gonococcal cervicitis and bacterial
      vaginosis are strongly associated with preterm delivery. The role of Chlamydia
      trachomatis, Trichomonas vaginalis and Ureaplasma urealyticum is less clear. By
      adopting a rational approach to the diagnosis and treatment of genitourinary
      infections, family physicians can substantially decrease a patient's risk of
      preterm delivery.

PMID- 11820489
TI  - How to write an evidence-based clinical review article.
AB  - Traditional clinical review articles, also known as updates, differ from
      systematic reviews and meta-analyses. Updates selectively review the medical
      literature while discussing a topic broadly. Non-quantitative systematic reviews
      comprehensively examine the medical literature, seeking to identify and
      synthesize all relevant information to formulate the best approach to diagnosis
      or treatment. Meta-analyses (quantitative systematic reviews) seek to answer a
      focused clinical question, using rigorous statistical analysis of pooled research
      studies. This article presents guidelines for writing an evidence-based clinical
      review article for American Family Physician. First, the topic should be of
      common interest and relevance to family practice. Include a table of the
      continuing medical education objectives of the review. State how the literature
      search was done and include several sources of evidence-based reviews, such as
      the Cochrane Collaboration, BMJ's Clinical Evidence, or the InfoRetriever Web
      site. Where possible, use evidence based on clinical outcomes relating to
      morbidity, mortality, or quality of life, and studies of primary care
      populations. In articles submitted to American Family Physician, rate the level
      of evidence for key recommendations according to the following scale: level A
      (randomized controlled trial [RCT], meta-analysis); level B (other evidence);
      level C (consensus/expert opinion). Finally, provide a table of key summary
      points.

PMID- 11820490
TI  - The newborn examination: part II. Emergencies and common abnormalities involving
      the abdomen, pelvis, extremities, genitalia, and spine.
AB  - Careful examination of the neonate at delivery can detect anomalies, birth
      injuries, and disorders that may compromise successful adaptation to extrauterine
      life. A newborn with one anatomic malformation should be evaluated for associated
      anomalies. If a newborn is found to have an abdominal wall defect, management
      includes the application of a warm, moist, and sterile dressing over the defect,
      decompression of the gastrointestinal tract, aggressive fluid resuscitation,
      antibiotic therapy, and prompt surgical consultation. Hydroceles are managed
      conservatively, but inguinal hernias require surgical repair. A newborn with
      developmental hip dysplasia should be evaluated by an orthopedist, and treatment
      may require use of a Pavlik harness. The presence of ambiguous genitalia is a
      medical emergency, and pituitary and adrenal integrity must be established. Early
      diagnosis of spinal lesions is imperative because surgical correction can prevent
      irreversible neurologic damage.

PMID- 11820491
TI  - Screening for lipid disorders in adults: recommendations and rationale.

PMID- 11820493
TI  - It sounds like child abuse--but is it?

PMID- 11820492
TI  - PHS guidelines for management of occupational exposure to HBV, HCV and HIV: HIV
      postexposure prophylaxis regimens.

PMID- 11820494
TI  - Determination of metals in wine with atomic spectroscopy (flame-AAS, GF-AAS and
      ICP-AES); a review.
AB  - Metals in wine occur at the mg l(-1) level or less and, though not directly
      related to the taste of the final product, their content should be determined
      because excess is undesirable, and in some cases prohibited, due to potential
      toxicity. Lead content in wine, for example, is restricted in several states by
      legislation to guarantee consumer health protection. Of several methods for metal
      determination, techniques of atomic spectroscopy are the most sensitive and
      rapid. Most of the elements present in wine can be determined with these
      techniques, at concentrations ranging from the mg l(-1) to the microg l(-1)
      level. Here, inductively coupled plasma-atomic emission spectrometry (ICP-AES),
      flame atomic absorption spectrometry (flame-AAS) and graphite furnace-atomic
      absorption spectrometry (GF-AAS) are compared for their characteristics as
      employed in metal determination in wine.

PMID- 11820495
TI  - Selective in vitro binding of dietary mutagens, individually or in combination,
      by lactic acid bacteria.
AB  - Specific strains of lactic acid bacteria possessing antimutagenic properties are
      suggested to remove mutagenic contaminants of foods through binding and an
      investigation of their substrate specificity is required. The ability of
      Lactobacillus rhamnosus strains GG and LC-705 in viable and non-viable (heat- and
      acid-treated) forms to remove both dietary mutagens and other aromatic dietary
      substrates from solution was studied using HPLC. Overall, removal increased in
      the order: caffeine = vitamin B12 =folic acid < ochratoxin A < aflatoxin B1 =
      PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine) < Trp-P-1 (3-amino-1, 4
      dimethyl-5H-pyrido[4,3-b]indole) (p < 0.05). Aflatoxin B1, Trp-P-1 and PhIP were
      removed in high amounts (77-95%) and ochratoxin A was removed in moderate amounts
      (36-76%). By contrast, only minimal amounts of caffeine, vitamin B12 andfolic
      acid were removed (9-28%). The significant removal of selected mutagens, but not
      other substrates, suggests these strains may be useful for dietary
      detoxification. Since exposure to multiple mutagens is likely, the removal of
      aflatoxin B1 and Trp-P-1 from a mixture of these substrates was also
      investigated. Removal of AFB1 significantly increased (p < 0.05) in the presence
      of Trp-P-1, while removal of Trp-P-1 significantly decreased (p < 0.05) in the
      presence of AFB1. Overall, no significant differences in removal were found
      between bacterial strains or between viable, heat- and acid-treated bacteria.

PMID- 11820496
TI  - Persistent organochlorine pesticide residues in milk and dairy products in India.
AB  - Monitoring of milk and dairy product samples of various brands from different
      cities in Maharashtra, India, was carried out to determine if there is any
      contamination due to organochlorine pesticide residues. The measurements were
      made using a gas chromatograph-electron capture detector system. Trace levels of
      DDT and HCH were detected in the samples. Total HCH levels in milk and milk
      product samples were lower than total DDT levels, which could be attributed to
      earlier extensive antimalaria sanitary activities. Butter had higher levels of
      DDT than cheese and milk powder. All levels of organochlorine pesticide residues
      in milk and milk products were well below the maximum permissible limits given by
      the FAO/ WHO. More importantly, as compared with an earlier report, present
      levels of the contaminants are substantially lower, which indicate the gradual
      phase out of these compounds.

PMID- 11820497
TI  - Occurrence of zearalenone in Korean barley and corn foods.
AB  - The presence of zearalenone (ZEN) in Korean foods such as barley, barley-based
      foods, corn, corn-based foods, fruits and vegetables was investigated by direct
      competitive enzyme-linked immunosorbent assay (dcELISA) and the liquid
      chromatography (LC) method. A total of 164 samples was collected from Seoul,
      Korea, in 1998 and 1999 including 30 barley, 32 barley-based foods, 18 corn, 47
      corn-based foods, 19 dried red pepper, nine dried jujube, and nine dried
      persimmon. Average recoveries of ZEN from barley and corn by dcELISA were 138 and
      145%, and by LC were 91 and 83% respectively at spiking levels of 5-500 ngg(-1).
      The detection limit for ZEN was 3 ng g(-1) by dcELISA and 4 ngg(-1) by LC. From
      164 samples analysed, ZEN was found by dcELISA in 35 samples (21%) with a mean
      level of 30 ng g(-1). Barley-based foods had the highest incidence of ZEN (38%)
      followed by barley (33%), corn-based foods (26%) and corn (22%). No ZEN was
      detected in any red pepper, jujube or persimmon samples. A high degree of
      correlation (r2 = 0.86) was observed between the 35 positive samples detected by
      dcELISA and 31 samples by LC.

PMID- 11820499
TI  - Analysis of food packaging UV inks for chemicals with potential to migrate into
      food simulants.
AB  - Ultraviolet (UV) inks are an alternative formulation system to the more usual
      paste or liquid inks (oils or solvents based) that dry mainly by evaporation or
      penetration into the printed substrate. Based on acrylic acid chemistry, UV inks
      dry (the exact term is 'curing') by the chemical process of photopolymerization.
      Their composition (acrylate monomers and oligomers together with photo
      initiators) exposed to UV emission lamps on the printing press units enable the
      transformation of the freshly printed ink layer into a tack-free film. For UV
      inks intendedfor primary food packaging, special care has to be paid to potential
      migrating species like small photo-initiator molecules and acrylate monomers not
      cross-linked in the formed network. The paper presents chromatographic methods to
      ascertain the level of ink ingredients potentially available to migrate into food
      simulants (migration tests). GC/MS was employed to quantify the levels of photo
      initiators or acrylic esters (acrylates).

PMID- 11820498
TI  - Fusarium toxins in wheat from an area in Henan Province, PR China, with a
      previous human red mould intoxication episode.
AB  - Wheat samples of the 1998 and 1999 crops from Puyang, an area in Henan Province,
      PR China with a previous human red mould intoxication episode, were analysed for
      trichothecenes and zearalenone (ZEA). For the 1998 Puyang crop, deoxynivalenol
      (DON) was the predominant toxin detected abundantly and frequently at a level of
      up to 14,000 microg kg(-1) (mean 2850 microgkg(-1)) in 30 of 31 (97%) wheat
      samples. Among these were 21 (70%) with a DON level that exceeded the Chinese
      regulation of 1,000 microg kg(-1). Nivalenol (NIV) and 15-acetyl-DON (15-ADON)
      were also found at 578 microg kg(-1) (one sample) and 59-1,800 microg kg(-1)
      (mean 365 microg kg(-1), 20 samples), respectively. ZEA co-occurred in 21 samples
      at 9-1,400 microg kg(-1) (mean 209 microg kg(-1)). Twenty-five (89%) wheat
      samples from Zhumadian, a region without a history of human red mould
      intoxication in the same province, contained low levels of DON (53-1240, mean 223
      microg kg(-1)) with seven (25%) co-contaminated with ZEA (10-217, mean 108 microg
      kg(-1)). All were free from 15-ADON and NIV. Significant differences in DON, 15
      ADON and ZEA concentrations between both areas were found. DON (<1000 microg kg(
      1)) and ZEA (5-111 microg kg(-1)) were also detected in the 1999 Puyang wheat.
      Proper environmental conditions for Fusarium species surviving winter combined
      with unusual high precipitation during wheat flowering were responsible for a
      high concentration of Fusarium mycotoxins in the 1998 Puyang wheat.

PMID- 11820500
TI  - Influence of solvent absorption on the migration of Irganox 1076 from LDPE.
AB  - The effect of solvent absorption on additive migration was studied by relating
      the diffusion coefficient (D) of Irganox 1076 to the maximum solvent absorption
      of different solvents in low-density polyethylene (LDPE) film. Solvents tested
      were ethanol, isopropanol, isooctane, ethylacetate, cyclohexane, tributyrin,
      tricaprylin and olive oil. Diffusion and partition coefficients were determined
      by fitting the migration curves, i.e. the concentration of Irganox 1076 in
      solvent as a function of time, with Fick 's diffusion equation. The results for
      the low molecular weight solvents show that with increasing maximum solvent
      absorption, D of Irganox 1076 is increasing as well. This trend is not
      observedfor the two triglycerides and olive oil. In spite of absorption, no
      increase in D was observed. The obtained result is the basis of an extended
      predictive migration model that, besides migrant and polymer properties, is also
      based on the maximum solvent absorption in the polymer.

PMID- 11820502
TI  - Effects of paraquat on essential antioxidant elements in osteogenic disorder
      Shionogi rat.
AB  - This study reports the effect of paraquat (PQ) on concentrations of four elements
      (Cu, Fe, Mg, Zn) in lung, kidney, spleen, liver, and heart of male osteogenic
      disorder Shionogi (ODS) rats, a strain not able to synthesize vitamin C. PQ
      significantly increased the Cu concentrations in lung, liver, and plasma,
      accompanied by a fall in renal levels. Fe levels were elevated in liver and
      spleen but lowered in plasma. PQ produced an increase in kidney Mg and a rise in
      liver Mg and Zn levels. Cardiac elemental levels were not affected by PQ
      treatment. PQ, a known oxidant, produced changes in tissue elements involved in
      antioxidant mechanisms.

PMID- 11820501
TI  - Safety and quality of food contact materials. Part 1: evaluation of analytical
      strategies to introduce migration testing into good manufacturing practice.
AB  - The results of a research project (EU AIR Research Programme CT94-1025) aimed to
      introduce control of migration into good manufacturing practice and into
      enforcement work are reported. Representative polymer classes were defined on the
      basis of chemical structure, technological function, migration behaviour and
      market share. These classes were characterized by analytical methods. Analytical
      techniques were investigated for identification of potential migrants. High
      temperature gas chromatography was shown to be a powerful method and 1H-magnetic
      resonance provided a convenient fingerprint of plastic materials. Volatile
      compounds were characterized by headspace techniques, where it was shown to be
      essential to differentiate volatile compounds desorbed from those generated
      during the thermal desorption itself. For metal trace analysis, microwave
      mineralization followed by atomic absorption was employed. These different
      techniques were introduced into a systematic testing scheme that is envisaged as
      being suitable both for industrial control and for enforcement laboratories.
      Guidelines will be proposed in the second part of this paper.

PMID- 11820503
TI  - Elevated blood mercury and neuro-otological observations in children of the
      Ecuadorian gold mines.
AB  - The prevalence of mercury (Hg) intoxication was investigated in 114 Andean
      Saraguro and non-Saraguro (Mestizo) children living in remote gold-mining
      settlements in Nambija and Portovelo, Ecuador. Venous blood samples showed a mean
      total blood mercury (B-Hg) level of 18.2 microg/L (SD 15.5; range 2-89.) for 77
      Saraguro and non-Saraguro children in the Nambija settlement, which was
      significantly higher than that of children in the Portovelo and reference groups.
      Comparison of groups showed mean B-Hg levels of 26.4 microg/L (range 4-89
      microg/L) for 32 indigenous/Saraguro children; 12.3 microg/L (range 2-33
      microg/L) for 45 non-Saraguro children; 4.9 microg/L (range 1-10 microg/L) for 37
      children in Portovelo; and 2.4 microg/L (range 1-6 microg/L) for a reference
      group of 15 children. Fisher's post hoc analysis revealed significant differences
      among groups, except between the Portovelo and the reference groups. Neuro
      otological symptoms and abnormalities were observed in Saraguro, non-Saraguro,
      and Portovelo children. Samples of soil collected at sites near the local school
      were found to contain Hg levels ranging from 0. 1 to 38 ppm, cadmium (Cd) levels
      from 0.07 to 0.82 ppm and arsenic (As) levels from < 1 to 3.9 ppm. in conclusion,
      the children of Nambija, particularly the Saraguro "Amer-Indians," exhibited
      elevated B-Hg levels from exposure to Hg used in the gold-mining process, and are
      at risk for neurological impairment. The children of Portovelo who reported neuro
      otological symptoms but had low B-Hg levels (<10 microg/L) may be affected by
      exposure to sodium cyanide, which is used extensively in the local gold-mining
      operations.

PMID- 11820504
TI  - Cord blood lymphocyte functions in newborns from a remote maritime population
      exposed to organochlorines and methylmercury.
AB  - The consumption of fish and sea mammals can be an important source of exposure to
      organochlorine compounds (OCs) and heavy metals in populations relying on seafood
      for subsistence. Exposure to these substances, especially during the prenatal
      period, has been shown to induce immunotoxic effects in mammals. Immunological
      status was assessed in 48 newborns from a remote maritime population living on
      the Lower and Mid North Shore of the St. Lawrence River (subsistence fishing
      group) and 60 newborns from the coastal urban center of Sept-Iles (reference
      group). Women were recruited upon arrival at Sept-Iles regional hospital to give
      birth. Cord blood samples were collected for organochlorine and heavy metal
      analyses and to isolate lymphocytes for immunological assays (proportions and
      functional responses of the main cellular subsets T, B, and NK (natural killer)
      cells. Concentrations of polychlorinated biphenyls (PCBs) and mercury were
      respectively three- and twofold higher, significantly greater, in the subsistence
      fishing group than in the reference group. Compared to the reference group, the
      subsistence fishing group showed significant decreases in the proportion of the
      naive helper T-cell subset CD4+CD45RA, T-cell proliferation following an in vitro
      mitogenic stimulation, and plasma immunoglobulin M (IgM) level, while plasma IgC
      level was increased. NK cytolytic activities were similar in both groups. The
      proportion of CD4+CD45RA cells was inversely correlated to mercury and PCBs,
      while T-cell clonal expansion was negatively associated with PCBs and p,p'-DDE.
      Mercury was inversely correlated to plasma IgM. Data show that subtle functional
      alterations of the developing human immune system may result from in utero
      exposure to OCs and mercury. Epidemiological studies are needed to determine the
      relevance of these alterations in predicting detrimental health effects in the
      developing child.

PMID- 11820506
TI  - Effects of pH and temperature on benzo[a]pyrene-DNA, -protein, and -lipid adducts
      in primary rat hepatocytes.
AB  - The effects of pH and temperature on benzo[a]pyrene(BaP)-DNA, -protein, and 
      lipid adducts were compared in rat hepatocytes treated with [3H]-BaP. In primary
      rat hepatocytes, BaP-DNA, -protein, and -lipid adducts were formed in a
      concentration-dependent manner (0.31-2.80 mmol BaP), and the formation of BaP
      lipid adducts, specifically triglyceride (TG) adducts, correlated well with that
      of DNA or protein adducts. As incubation time increased (1-24 h), the formation
      of DNA or protein adducts was also elevated, while BaP-TG adducts decreased after
      3 h of reaction. pH had no effect on the formation of [3H]-BaP-DNA, and -protein
      adducts, and the TG adducts decreased with increasing pH (3.4-11.4). With an
      increase in incubation temperature (30-45 degrees C), on the other hand, the
      adduct formation was increased with increasing temperature up to 40 degrees C and
      then decreased sharply. These results suggest that the physicochemical properties
      of BaP-DNA, -protein, and -TG adducts might be important to consider when cells
      or humans who have been exposed to BaP are monitored for biomarkers.

PMID- 11820505
TI  - Prolongation of human neutrophil survival by low-level mercury via inhibition of
      spontaneous apoptosis.
AB  - Low levels of organic and inorganic mercury compounds have been reported
      previously to induce cell death by apoptosis in human peripheral blood
      mononuclear cells (MNC). but little is known about their potential effects on the
      viability and death of polymorphonuclear neutrophils (PMN). In contrast to MNC,
      PMN are known to undergo readily spontaneous apoptosis both in vivo and in vitro.
      Therefore, it was hypothesized that PMN may differ from MNC in their reactions to
      low mercury levels. The effects of methylmercuric chloride (MeHgCl) and mercuric
      chloride (HgCl2) were evaluated in concentration-response and time-course studies
      on human PMN viability and on their modes of cell death after in vitro incubation
      at 37 degrees C. Cell death by apoptosis or necrosis was assessed by annexin V
      fluorescein isothiocyanate binding to externalized phosphatidylserine in
      conjunction with propidium iodide, and flow cytometry analysis. Morphologic
      counting of pyknotic nuclei and the fluorescence properties of the DNA-binding
      dye Hoechst 33342 in combination with propidium iodide were used to further
      confirm apoptotic cell death and to characterize the sequence of Hg-induced cell
      death. Results show that low concentrations of MeHgCl (1-7.5 microM) that were
      cytotoxic to MNC actually inhibited PMN spontaneous apoptosis. Low-level HgCl,
      reproduced the anti-apoptotic effects of MeHgCl on PMN, but to a lower extent.
      Higher concentrations of MeHgCl and HgCl2 were necrogenic to PMN, but MeHgCl was
      about an order of magnitude more toxic, and discrete differences were observed in
      the modalities of cell death induced by both species. These data reveal for the
      first time that (1) low levels of organic and inorganic mercury species protect
      human PMN from cell death via inhibition of spontaneous apoptosis, and (2) PMN
      are more resistant than MNC to mercury-induced cytotoxicity. Since delayed
      apoptosis and increased resistance to toxicant-induced cell death may lead to
      excessive accumulation of senescent PMN, evidence indicates that findings of this
      study may have implications for mercury-induced autoimmunity and inflammation.

PMID- 11820507
TI  - Pharmacokinetics of a benzodithiin (RD3-0028) following aerosol treatment in rat.
AB  - 1. RD3-0028, a benzodithiin compound, has potent antiviral activity against
      respiratory syncytial virus (RSV) in cell culture. The compound also inhibits
      growth of RSV and improves pathologic changes of interstitial pneumonia in the
      immunosuppressed mouse when delivered by small-particle aerosol. 2. In the
      present study, the absorption, distribution and excretion of 14C-RD3-0028 were
      compared in rat following either a single aerosol treatment or oral
      administration. 3. The plasma concentration was maintained at the same level from
      5 min to 1 h, and decreased with a half-life of 2.2 +/- 0.1 h for 1-8 h. 4. The
      excretion of radioactivity in the urine and faeces at 24 h after aerosol
      treatment was 89.3 and 4.5%, respectively, indicating that almost all the
      radioactivity was rapidly excreted in the urine. The excretion of total
      radioactivity was 98.9% within 168 h. 5. The concentrations of radioactivity in
      the lung and trachea following aerosol treatment were higher than those in other
      tissues, and were detected even at 72 h. 6. These results suggest that the
      aerosol treatment might be useful for delivering RD3-0028 to the respiratory
      tract of RSV-infected patients.

PMID- 11820508
TI  - N-O glucuronidation: a major human metabolic pathway in the elimination of two
      novel anti-convulsant drug candidates.
AB  - 1. The urinary metabolites of the anti-convulsant compound 4-amino-1-(2,6
      difluorobenzyl)-1H-1,2,3-triazolo[4,5-c]-pyridine hydrochloride (GI265080)
      obtained following a single oral dose to man have been detected and quantified
      relative to each other using 19F-NMR spectroscopy. 2. The human urinary
      metabolites of GI265080 were isolated using semipreparative HPLC and
      unequivocally characterized using 1H-NMR spectroscopy, two-dimensional
      heteronuclear NMR spectroscopy and mass spectrometry. The assignments of the N
      (5)-oxide and the N-(5)-O-glucuronide metabolites of GI265080 were further
      confirmed by independent synthesis. The urinary metabolites obtained following
      single oral doses to dog and rat have also been isolated and characterized. 3.
      The human urinary metabolites of GI265080 comprise the N-(5)-oxide, the
      quaternary N+-(5)-glucuronide, the 7-hydroxy glucuronide and a glucuronide
      conjugate of the N-(5)-oxide. The N-(5)-O-glucuronide conjugate is a novel
      species in human metabolism and is a significant route of elimination of GI265080
      in man. 4. The urinary metabolites of the potential anti-convulsant GW273293 (6
      amino-3-(2,3,5-trichlorophenyl)pyrazin-2-ylamine) obtained following a single
      oral dose to man have also been isolated and characterized. The formation of a
      novel N-O-glucuronide was also observed and was shown to constitute a significant
      route of elimination of GW273293 in man.

PMID- 11820509
TI  - Comparative metabolism of genistin by human and rat gut microflora: detection and
      identification of the end-products of metabolism.
AB  - 1. Biotransformations by gut microflora play a pivotal role in determining the
      biological activity of isoflavones that occur in soya-based foods predominantly
      as betaglycosyl conjugates. Microflora prepared from rat caecae and human faeces
      were used to investigate the metabolic fate of genistein beta-glycosides
      extracted from soya flour. The end-products of such metabolism were determined by
      parallel incubations of microflora with [2',3,5',6'-3H] and [4-14C]-labelled
      genistein. 2. Quantitative analysis by LC-MS/IS indicated very rapid and complete
      degradation of genistin, which was associated with a transient increase in
      genistein. Qualitative studies indicated that the malonyl and acetyl glycosides
      of genistein were also degraded by the microflora. 3. Incubation of caecal and
      faecal microflora with [3H] and [14C]genistein yielded similar radiolabelled
      metabolites, which were identified by radio-LC-MS(n) as the intermediates
      dihydrogenistein and 6'-hydroxy-O-desmethylangolensin and end-product 4
      hydroxyphenyl-2-propionic acid. This profile of genistein metabolites indicated
      selective hydrolysis of 6'-hydroxy-O-desmethylangolensin between carbon atoms 1'
      and 1 to yield the end-products 4-hydroxyphenyl-2-propionic acid and 1,3,5
      trihydroxybenzene. 4. The biological significance of the products of genistein
      metabolism warrant further investigation since they may play an important role in
      mediating the beneficial antioxidant health effects associated with the
      consumption of isoflavones in food.

PMID- 11820511
TI  - Biotransformation of benzydamine by microsomes and precision-cut slices prepared
      from cattle liver.
AB  - 1. Benzydamine (BZ), a non-steroidal anti-inflammatory drug used in human and
      veterinary medicine, is not licensed for use in food-producing species.
      Biotransformation of BZ in cattle has not been reported previously and is
      investigated here using liver microsomes and precision-cut liver slices. 2. BZ
      was metabolized by cattle liver microsomes to benzydamine N-oxide (BZ-NO) and
      monodesmethyl-BZ (Nor-BZ). Both reactions followed Michaelis-Menten kinetics (Km
      = 76.4 +/- 16.0 and 58.9 +/- 0.4 microM Vmax = 6.5 +/- 0.8 and 7.4 +/- 0.5
      nmolmg(-1) min(-1) respectively); sensitivity to heat and pH suggested that the N
      oxidation is catalysed by the flavin-containing monooxygenases. 3. BZ-NO and Nor
      BZ were the most abundant products derived from liver slice incubations, and nine
      other BZ metabolites were found and tentatively identified by LC-MS.
      Desbenzylated and hydroxylated BZ-NO analogues and a hydroxylated product of BZ
      were detected, which have been reported in other species. Product ion mass
      spectra of other metabolites, which are described here for the first time,
      indicated the formation of a BZ N- -glucuronide and five hydroxylated and N+
      glucuronidated derivatives of BZ, BZ-NO and Nor-BZ. 4. The results indicate that
      BZ is extensively metabolized in cattle. Clearly, differences in metabolism
      compared with, for example, rat and human, will need to be considered in the
      event of submission for marketing authorization for use in food animals.

PMID- 11820512
TI  - The folded deckchair position: the problem of long-haul flights.

PMID- 11820510
TI  - Metabolism and urinary excretion of a new quinoline anticancer drug, TAS-103, in
      humans.
AB  - 1. TAS-103, a novel condensed quinoline derivative, has been developed as an
      anticancer drug targeting topoisomerases I and II. 2. The purpose of the present
      study was to characterize the metabolism and urinary excretion of TAS-103 after
      the intravenous infusion of a single dose to patients in Phase I clinical trials.
      3. Five metabolites were detected using high-performance liquid chromatography
      (HPLC) photodiode array and a precursor scan by liquid chromatography mass
      spectrometry mass spectrometry (LC/MS/MS). 4. Structures of the five metabolites
      were determined using the results of enzymatic hydrolysis and the analysis of
      production mass spectra obtained by LC/MS/MS, and by comparing HPLC retention
      times and UV, mass and production mass spectra of authentic standards. 5. The
      metabolites were identified as demethyl-TAS-103 glucuronide (DM-TAS-103-G), TAS
      103 glucuronide (TAS-103-G), TAS-103 glucuronide N-oxide (NO-TAS-103-G), demethyl
      TAS-103 (DM-TAS-103) and TAS-103 N-oxide (NO-TAS-103). 6. The mean total amount
      of TAS-103 and TAS-103-G in urine was only 6.03% of the dose, suggesting that
      urine is not the main elimination route. TAS-103 was extensively metabolized, and
      a small percentage of the parent drug (0.41%) was found in urine.

PMID- 11820513
TI  - Osteoporosis in anorexia nervosa.

PMID- 11820514
TI  - Diagnosis, treatment and management of osteoporosis in the orthopaedic setting.

PMID- 11820515
TI  - Influenza vaccination uptake in 1999 and older persons recall of vaccination.
AB  - The aims of this study were to assess the uptake of the influenza vaccine by
      medical card patients aged 65 years and older and to assess if using older
      persons' recall of vaccination was a reliable method of assessing uptake. A
      questionnaire was mailed to 360 medical card patients aged 65 years and older and
      from the returns a subset were selected and the GPs contacted to ascertain
      whether the patients had received the vaccine or not. A total of 293
      questionnaires were returned (response rate of 81.4%). One hundred and forty-four
      (49.1%) stated that they received the influenza vaccine. GPs were contacted in
      respect of 64 patients to check on their vaccination record. Only 2 (3.1%) of the
      questionnaires differed to the GP records in respect of vaccination. The result
      being that the uptake rates as assessed by the patients' recall and by checking
      GPs records were almost identical. (Kappa statistic: 0.94) In conclusion the
      uptake for older persons with medical cards was low at 49.1%. Using older persons
      recall to estimate uptake is valid and accurate.

PMID- 11820516
TI  - An audit of the ophthalmic division of the accident and emergency department of
      the Royal Victoria Eye and Ear Hospital, Dublin.
AB  - The objective was to study the patterns of emergency department visits and to
      make recommendations on ways of improving the service. Patients' demographic
      data, diagnoses, source of referral and follow-up were entered onto a database.
      Three thousand seven hundred consecutive patients' visits over a six-week period
      were entered. The average daily attendance ranged between 80-100 people. 54% of
      patients were self-referrals. 20% had a previous visit to the hospital. 17% were
      referred from a GP, 5% from another hospital and 3% from opticians. Superficial
      injury to the eye and ocular adnexae was the most common diagnostic category. 56%
      of patients were discharged at the first visit. 23% returned for review to
      casualty. 14% were referred to OPD, 3% directly to a consultant for review and 1%
      were admitted to hospital. Waiting times for consultation for patients was highly
      variable ranging from thirty minutes to five hours, mean two hours. The
      department provides a service far in excess of its defined function. Non urgent
      problems accounted for as much as 60-70% of all emergency department visits.
      Improvement of ophthalmic training of GPs, introduction of an ophthalmic triage
      system and expansion of outpatient services is recommended so that casualty
      remains a genuine emergency service and not a primary care service with
      uncontrollable numbers and unacceptable waiting times for patients.

PMID- 11820517
TI  - Use of inferior vena cava filters in thromboembolic disease two case reports with
      a literature review.
AB  - Inferior Vena Cava (IVC) filters are used in cases of documented pulmonary
      embolism (PE) where anticoagulation is contraindicated or has failed.
      Increasingly, they are being used prophylactically in preoperative patients at
      high risk of embolism. This latter group includes patients with free-floating
      caval, iliac or femoral vein thrombi. Filters may be permanent (eg Greenfield),
      temporary (eg Antheor, Gunther) or retrievable (eg Gunther Tulip). This last type
      of filter is becoming increasingly popular. We present two recent cases in which
      retrievable filters were intentionally used, with good results. A recent
      literature review is included.

PMID- 11820518
TI  - Expandable metal stents in the palliation of malignant dysphagia and oesophageal
      respiratory fistulae.
AB  - The use of self expandable metal stents in the palliation of malignant dysphagia
      and oesophago-respiratory fistulae has increased in recent years. The aim of this
      study was to report a comprehensive 4 year audit of a Specialist Unit's
      experience with the expandable stent. 200 expandable metal stents were deployed
      for palliation of non operable malignant dysphagia or fistulae. Per-operative,
      early (<30 days) and late (>30 days) complications specific to the stent were
      documented. Stents were successfully positioned in all patients. There was no
      mortality associated with the insertion and no perforation. Dysphagia was
      palliated initially in 93 per cent of cases. The mean dysphagia score improved
      significantly from 3.2 to 1.5 (p<0.01). This significant benefit persisted at 3
      months and 6 months of follow-up. The commonest complication was stent migration
      (5.5%) and 23 patients (11%) required a second stent insertion. Oesophago
      respiratory fistulae were successfully palliated in all cases. This study
      demonstrates the effectiveness of self expandable metallic stents in the
      palliation of non operable malignant dysphagia and oesophago-respiratory
      fistulae. The minimal risk of significant complications and low incidence of
      reintervention should establish this approach as first line palliation in these
      patients.

PMID- 11820519
TI  - A review of family planning services by general practitioners in a health board
      region.
AB  - In 1994 the North Eastern Health Board published a study, which ascertained the
      range of family planning services provided by General Practitioners (GPs) in the
      area. This study highlighted some service and training needs, which have since
      been addressed. This study has been repeated to evaluate service developments.
      All GPs on the NEHB mailing list were sent a pre-piloted questionnaire about the
      range of family planning services they provide, their referral patterns should
      they not provide the service themselves and their comments on how the health
      board could assist in the enhancement of family planning services. The data were
      analysed using the software package JMP and statistical analysis was carried out
      using either the Chi-square test or Fishers exact test. There was a response rate
      of sixty six percent. There has been a decrease in the number of GPs in single
      handed practices (24% vs 50% in 1994) and an increase in the number of practices
      who employ a practice nurse. Almost one third of GPs providing family planning
      services are women (18% in 1994) and over half of GPs hold a family planning
      certificate (33% in 1994). The range of services provided has increased and more
      GPs are now fitting intrauterine contraceptive devices (19% vs 14%). This study
      highlights significant developments in the family planning service and indicates
      that general practice is capable of providing a fully comprehensive service.

PMID- 11820520
TI  - Asymptomatic ascariasis infection in a child.

PMID- 11820522
TI  - The hazards of intra-oral piercing.

PMID- 11820521
TI  - Persistence of vancomycin-resistant enterococci (VRE) and other bacteria in the
      environment.

PMID- 11820523
TI  - Spinal osteomyelitis and related septic complications in a patient with an
      infected peripheral venous cannula site.

PMID- 11820524
TI  - Psychiatry and the legal system.

PMID- 11820525
TI  - Fibrosing skin condition among patients with renal disease--United States and
      Europe, 1997-2002.
AB  - During May 1997-November 2000, eight (3%) of 265 kidney transplant recipients at
      a hospital in California developed an unusual skin condition posttransplant
      (Figure 1). On clinical examination, the patients had fibrotic skin lesions
      histologically resembling scleromyxedema on their distal extremities and trunk,
      resulting in severe contractions and limited mobility. However, the usual IgG
      lambda paraprotein associated with scleromyxedema was not observed in these
      patients. Personnel in the dermatopathology section at the University of
      California, San Francisco, reviewed the biopsies and concluded that this skin
      disorder had not been described previously. As a result, health-care providers at
      the hospital where the index patient was treated asked the California Department
      of Health Services (CDHS) and CDC to assist in the investigation. This report
      summarizes preliminary findings from the investigation.

PMID- 11820526
TI  - Respiratory syncytial virus activity--United States, 2000-01 season.
AB  - Respiratory syncytial virus (RSV) has a worldwide distribution and can cause
      serious lower respiratory tract illness (LRTI). RSV is most commonly considered a
      pathogen among infants and young children; however, it can cause serious LRTI
      throughout life, especially among those with compromised respiratory, cardiac, or
      immune systems and the elderly. In temperate climates, RSV infections occur
      primarily during annual outbreaks, which peak during winter months. In the United
      States, RSV activity is monitored by the National Respiratory and Enteric Virus
      Surveillance System (NREVSS), a laboratory-based surveillance system. This report
      summarizes trends in RSV activity reported to NREVSS during July 2000-June 2001
      and presents preliminary surveillance data from the weeks ending July 7 through
      December 8, 2001, indicating the onset of the 2001-02 RSV season. Health-care
      providers should consider RSV in the differential diagnosis of lower respiratory
      tract disease in persons of all ages, use isolation procedures to prevent
      nosocomial transmission, and consider use of immune globulin or monoclonal
      antibody prophylaxis in premature infants or infants and children with chronic
      lung disease.

PMID- 11820527
TI  - Lyme disease--United States, 2000.
AB  - Lyme disease (LD) is caused by the tickborne spirochete Borrelia burgdorferi
      sensu lato and is the most common vectorborne disease in the United States. CDC
      initiated LD surveillance in 1982, and the Council of State and Territorial
      Epidemiologists designated it a nationally notifiable disease in 1991. This
      report summarizes the 17,730 cases of LD reported to CDC during 2000, which
      indicates that more LD cases were reported in 2000 than in any previous reporting
      year and that the reported incidence of LD is greatest in the northeastern, mid
      Atlantic, and north-central regions of the United States. LD can be prevented by
      reducing tick populations, avoiding tick-infested habitats, using repellents,
      promptly removing attached ticks, and vaccination.

PMID- 11820528
TI  - Recommended childhood immunization schedule--United States, 2002.
AB  - Each year, CDC's Advisory Committee on Immunization Practices (ACIP) reviews the
      recommended childhood immunization schedule to ensure that it is current with
      changes in manufacturers' vaccine formulations, has revised recommendations for
      the use of licensed vaccines, and has recommendations for newly licensed
      vaccines. This report presents the recommended childhood immunization schedule
      for 2002, which has remained the same in content since January 2001 but has a
      redesigned format.

PMID- 11820529
TI  - Who will look after my grandmother? Attitudes of student nurses toward the care
      of older adults.
AB  - A review of the literature illustrates the unpopularity of nursing in the elderly
      population related to other areas of nursing practice. The aim of this article is
      to present the findings of a research project conducted in Victoria, Australia,
      investigating the career preferences of undergraduate nursing students. The
      results indicate caring for older adults is considered the least popular area of
      practice for Year 1 nursing students. The reason given by students for their
      choices demonstrates a negative view of this type of work, largely based on
      inaccuracies and misconceptions. The implications of these findings for the
      future care of elderly individuals are discussed.

PMID- 11820530
TI  - Drug & alcohol intervention for older women: a pilot study.
AB  - Pretest and posttest information was gathered from 26 older women attending
      educational programs related to alcohol and drug use. The goals of the study were
      to determine current knowledge about alcohol and drugs among older women and to
      gather some initial information about the potential for alcohol and drug
      interactions and misuse. The intervention included a 60-minute presentation on
      the metabolism of alcohol and drugs in the aging body, the potential for alcohol
      drug interactions, and a discussion of healthy lifestyles (e.g., diet, exercise).
      Older women, especially those who were moderate to heavy drinkers, were found to
      have many misconceptions about alcohol and drug use, but their knowledge improved
      dramatically after the brief educational intervention. This finding may suggest
      that most of the women had knowledge deficits rather than deeply entrenched
      attitudes about alcohol and drug use or alcohol dependence. Therefore, simple
      educational interventions may be very effective with this subset of women.

PMID- 11820533
TI  - Helping older adults cope with the nation's tragedy.

PMID- 11820531
TI  - Barriers to nutrition care for nursing home residents.
AB  - The prevalence of protein-calorie malnutrition (PCM) in nursing home residents
      has reached 85% in some nursing homes and is linked to increased mortality among
      residents. Separate survey questionnaires were developed and administered to 99
      nursing assistants and 44 nurses (35 RNs, 9 LPNs) from five eastern Washington
      nursing homes. The purpose was to assess nurse (RN, LPN) and nursing assistant
      perceived beliefs and views related to nutritional needs of nursing home
      residents that have a potential impact on PCM of residents. Experienced nursing
      assistants did not view the nurse as an active participant during mealtime.
      Specific barriers such as a lack of time and training, too many residents,
      working short staffed, poor food quality, and a lack of nurse-nursing-assistant
      teamwork may contribute to residents not getting enough food to eat. An education
      program addressing staff relationships and nutrition training of nursing
      assistants could improve the ability of nursing staff to ensure residents' food
      intake and improve the quality of life for residents in nursing homes.

PMID- 11820534
TI  - Nurse caregiver feelings about agitation in Alzheimer's disease.
AB  - This study examines the feelings of nurse caregivers of patients with Alzheimer's
      disease (AD) who are agitated. Methods included participant observation,
      examination of medical records, and ethnographic interviews of 17 nurse
      caregivers from one inpatient setting. Two patterns of feelings emerged from the
      data. One pattern was associated with caregiver expressions of personal
      identification with and vulnerability to AD. These nurses endorsed feelings of
      helplessness, men hopelessness, and frustration when providing care to agitated
      AD patients. A second pattern situated nursing interactions within the realistic
      context of the patient's response to the illness. Caregiver feelings of
      confidence, competence, and satisfaction were associated with the second pattern.
      The relationship between the feeling states of nurse caregivers and their
      reported management of agitation in AD is discussed. Recognition and awareness of
      distressing feelings is a necessary first step for nurses to learn less
      personalized reactions to patients and respond more objectively to agitated
      behaviors.

PMID- 11820535
TI  - Graduate programs in gerontological nursing find it difficult to recruit
      students. What suggestions do you have to improve recruitment?

PMID- 11820537
TI  - Big public policy issues face gerontological nursing.

PMID- 11820536
TI  - A memo to geropsychiatric nurses: let's act out!

PMID- 11820538
TI  - Primary health care.

PMID- 11820539
TI  - The public health problem of acute respiratory illness in childcare.
AB  - Acute respiratory illness continues to be a significant problem for children
      attending childcare. The problems for the child are in terms of prevalence,
      incidence, and quality of life. Additional costs relate to parental absence from
      work and loss of earnings. This paper reports on the literature, and notes that
      little research has been undertaken to determine whether there are long-term
      risks or benefits to experiencing acute respiratory illness in early childhood.
      Research to date is presented, and the role of public health nurses is discussed
      in relation to how they might assist in reducing the incidence/prevalence of
      acute respiratory illness in children attending childcare.

PMID- 11820541
TI  - Functionalism and holism: community nurses' perceptions of health.
AB  - This paper reports the results of a study that was designed to explore and
      examine the perceptions of two groups of newly qualified community nurses about
      the factors they considered to be embedded within the concepts of health, health
      enhancing behaviours at individual, family and community levels and their
      'innermost self'. The research was exploratory in nature, and included two sample
      groups: group 1 comprised 16 newly qualified health visitors; group 2 comprised
      16 newly qualified community mental health nurses. Purposive sampling was used
      and data were collected using semi-structured interviews. The group of health
      visitors perceived health in terms of physical fitness and functional states. At
      a global level they perceived the need to provide education on health matters.
      They gave generously to 'charities' and perceived the 'inner self' as 'that part
      that matters'. The group of community mental health nurses perceived health in
      terms of holism and being states. Their concept of health was related to
      listening to each individual's perception of what is 'right' and 'health
      enhancing' for them. At a global level they considered the protection of the
      ozone layer and the promotion of a just and equitable society which focused on
      the reduction of poverty, to be key health-enhancing activities. They perceived
      their 'innermost self' to be 'that part of me that makes life worth living', and
      the soul. The findings have implications for developing new and creative
      approaches for teaching the holistic concept of health and healing. Educational
      activities could be designed which strive to ensure that nurses themselves have
      safe and health embracing opportunities for exploring all the elements that are
      embedded within the topic of health. Their role in facilitating holistic health
      promoting activities for all clients also needs to be addressed.

PMID- 11820540
TI  - Living the revolution: Cuban health workers.
AB  - The cuban government has placed a very high emphasis on health since 1959 and
      vaccination and health education campaigns, as well as access to a comprehensive
      free healthcare system, have contributed to dramatic improvements in the
      population's health status. Much that has been written about the Cuban health
      service has relied on published sources, but this article is based on 18 months
      spent carrying out ethnographic fieldwork in the country, with particular
      emphasis on the daily lives of women employed in the health sector. Data were
      collected by participant observation, interviews and life-story work. Family
      doctors are usually young women completing their specialist training. They work
      in health centres in apartment blocks in which they also live. They work closely
      with nurses and other health and social service workers. Health workers are
      expected to live and work in their own communities, to act as role models for
      their patients, and to be available at all times. Whilst this has led to an
      extremely well-informed population and accessible healthcare, it has brought
      costs to healthcare workers in terms of very high expectations, a feeling that
      they do not have a private life, and stress caused by the inability to meet
      patient demands in the face of shortages of medicines and other supplies as a
      result of the continuing US trade blockade. These pressures and frustrations for
      healthcare workers may have parallels in Western healthcare services which are
      subject to resource constraints.

PMID- 11820542
TI  - Nursing in the community--impact of context on the practice agenda.
AB  - The agenda for health care detailed in recent policy statements has a strong
      community and primary health care focus. The impact of the community, and
      specifically the patient's home, as a location for practising and learning to
      practise nursing, is an issue which has received limited exploration. Recent
      research suggests that the context influences the practice agenda in a number of
      ways. Highlighting the impact of working in the community context is timely in
      order that education providers, policy makers and managers are fully aware of the
      impact of moving care 'closer to home'.

PMID- 11820543
TI  - The role of district nurses in caring for people with mental health problems who
      live in rural settings.
AB  - District Nurses in rural areas frequently fulfil, in some permutation, the
      functions of district nursing, health visiting, school nursing, and community
      midwifery. This complex role can bring them into contact with a wide range of
      mental health problems. The extent, nature and type of mental health problems,
      and their response to these problems, is not well documented in the literature.
      The findings of this qualitative study indicate that District Nurses do in fact
      have contact with a wide range of mental health problems. The role of District
      Nurses in caring for this client group is more substantial than has been
      previously recognized. It is suggested that this role be formally acknowledged
      and that systems put in place to optimize the effectiveness of District Nursing
      interventions.

PMID- 11820544
TI  - Developments in nursing practice in primary health care in Hong Kong:
      opportunities and challenges.
AB  - The significance of primary health care to the health of individuals and
      communities has been well established but the development of primary health care
      and nursing practice within the context of primary health care remains varied in
      different countries and settings. This paper focuses on developments in nursing
      practice in primary health care in Hong Kong, using three community-based
      research projects to identify the opportunities and challenges created for nurses
      working in these settings. The projects were established in response to
      identified health needs and to target cancer education, HIV/AIDS and chronic
      health problems. Opportunities include the development of professional autonomy,
      innovative approaches to clinical practice, and developing skills in working with
      a diverse range of professionals and communities. Challenges include managing
      uncertainty and the development of evaluation systems to demonstrate health gains
      from nursing interventions.

PMID- 11820545
TI  - Evaluating a community nursing service: listening to the voices of clients with
      an intellectual disability and/or their proxies.
AB  - The aim of this study was to evaluate a specialist nursing service programme for
      people with an intellectual disability residing in the community. It is important
      to correct the imbalance in the literature that has neglected the voices of the
      clients themselves or denied expression by their proxies. The aim of the study
      was to gain a better understanding of matters of importance for clients and their
      families and to involve them in the evaluation of a service that directly affects
      their care. Only three clients were able to participate; however, 17 parents
      (next of kin) agreed to be interviewed. In-depth interviews were audio-taped,
      transcribed and analysed relating to the questions asked and were checked against
      the domains of the nursing practice in the disability area: continuity of care,
      advanced nursing practice, education and credentialling, personal and
      professional attributes, primary health care, and normalization. The findings
      confirm the high regard in which the programme is held. Service evaluation is
      crucial in providing evidence for programme funders. The favourable outcome of
      this evaluation meant that the programme gained funding for another few years.

PMID- 11820547
TI  - Evidence-based practice: tap water cleansing of leg ulcers in the community.
AB  - To establish and encourage wound management practices based on evidence, a
      Community Nursing Organization in metropolitan Adelaide began a series of
      research initiatives in 1997. Based on the results of a wound management survey,
      and through the processes of participatory action research with clinicians, many
      wound management practice changes were instigated throughout the Community
      Nursing Organization. One question remains unanswered: What is the evidence for
      the use of sterile saline or clean tap water for cleansing of leg ulcers in the
      community? In this paper we describe a project where we applied the three
      principles of planning, action and evaluation. Application of these principles
      enabled clinicians to collaborate in the search for evidence to support or refute
      tap water cleansing of leg ulcers. To conclude, we report on a pilot research
      project undertaken to obtain further evidence either to support or refute the use
      of tap water cleansing for leg ulcers in the community.

PMID- 11820546
TI  - Towards the eradication of head lice: literature review and research agenda.
AB  - Head lice infestation is a public health issue. In the effort to compile an
      evidence-base about the physiology, detection, treatment, effects and management
      strategies of head lice infestations we reviewed current literature. This
      literature signalled significant evidence gaps and these gaps provide incentives
      for further research. Our conclusions from the literature are that parents of
      children are responsible for head lice detection and treatment but have varying
      access to advice about how best to treat this condition. Concern is exacerbated
      by misconceptions surrounding the circumstances of infestation. Head lice are a
      low priority for health professionals in Australia, whereas parents and teachers
      believe the problem necessitates greater attention. It is important to provide a
      unified evidence-based approach to good information. It is timely for health care
      professionals to re-examine and prioritize this public health issue. They should
      research and work collaboratively towards the eradication of head lice.

PMID- 11820548
TI  - Staff activities and behaviour are the source of many feelings: relatives'
      interactions and relationships with staff in nursing homes.
AB  - Family members do not give up their involvement in the life of their older
      relatives when they move to an institution. Relatives feel that it is they who
      take the initiative to establish a working relationship with the staff at the
      nursing home. Relatives want more spontaneous information from staff,
      particularly about residents' daily lives, and there is a need for relatives to
      have opportunities to talk with staff under relaxed conditions. Staff behaviour
      and activities towards residents and relatives are a source of many feelings for
      relatives. Relatives' understandings of the challenges faced by staff are not
      communicated to staff, nor are positive or negative experiences explicitly passed
      on to staff.

PMID- 11820549
TI  - Elders' needs and experiences of receiving formal and informal care for their
      activities of daily living.
AB  - Older people living in the community or institutional settings are more likely to
      require help with their activities of daily living, with women more likely than
      men to need some help. The interviews in this qualitative study were conducted
      with a convenience and purposive sample of 20 elders living in Southeast
      Washington, USA, at home or in institutional settings, receiving informal or
      formal health care. Findings related to personal and instrumental activities of
      daily living are reported and include elders' experiences and views relating to
      the help and assistance they receive. The majority of elders needed help with
      their instrumental activities of daily living, provided by informal networks,
      whether living at home or in institutional settings. This help constituted social
      care. Formal health care with personal activities of daily living was required
      only by a minority of elders and constituted those with the greatest disability
      and dependency.

PMID- 11820550
TI  - Elders' perceptions of formal and informal care: aspects of getting and receiving
      help for their activities of daily living.
AB  - A purposive and convenience sample of 16 women and four men receiving informal
      and formal care for their activities of daily living either at home or
      institutions in Southeast Washington, USA was interviewed. Qualitative findings
      related to asking for help, getting and receiving help, interpersonal aspects of
      receiving help, and met and unmet needs are reported. Some seniors found it more
      difficult to ask for and accept help and there were gender differences, with men
      tending to adopt a more logical and pragmatic approach while women viewed
      receiving help as a loss of independence and an invasion of privacy. Intimacy and
      nudity were also threats for women. Three styles of adjustment and acceptance
      were identified within the data and related to positive acceptance, resigned
      acceptance and passive acceptance. There appeared to be a relationship between
      independence and control, with elders losing some independence but retaining
      control through choice, payment and involvement in decision making. Reciprocity
      was found to bring added value to relationships between care providers and
      elders, with a rhythm and symmetry developing in relationships where needs were
      known, anticipated and met. Seniors should be encouraged to plan for their future
      and to find out about local help and services available to them in advance of
      their requiring any assistance.

PMID- 11820551
TI  - Placing a spouse in a care home: the importance of keeping.
AB  - Despite a universal policy of community care, the number of frail older people
      entering care homes is likely to increase in the future. There have been
      relatively few studies exploring the experience of spouses who have placed a
      partner in care. Due to a lack of preparation, the placement process is often ad
      hoc, with little attention being given to spouses' emotional reactions or their
      efforts to maintain their relationship with their partner. The relationship
      between care home staff and families is often superficial and strained. There is
      a need for more proactive efforts to facilitate a partnership between care home
      staff and families.

PMID- 11820552
TI  - Detection of delirium using the confusion assessment method.
AB  - Delirium in hospitalized elderly patients is a phenomenon requiring a lot of
      nursing attention. It is also a disorder contributing to poor health outcomes in
      this population. Because of their 24-hour work schedule, nurses are frequently
      the first to observe acute changes in patients' mental health status and to
      initiate early interventions. However, delirium is not always easily identified.
      Therefore, the goal of this article is to increase nurses' knowledge and
      awareness of early signs of delirium using the Confusion Assessment Method (CAM)
      routinely and systematically.

PMID- 11820553
TI  - "I hated those darn chickens...": the power in stories for older adults and
      nurses.
AB  - Attention to stories provides a holistic view of an older adult and offers the
      potential for quality nursing intervention. Explored in this article is the power
      of stories to advance the well being of older adults and the implications for
      gerontological nurses of a commitment to support storytelling in this population.

PMID- 11820554
TI  - The effect of individualized activities on the sleep of nursing home residents
      who are cognitively impaired: a pilot study.
AB  - This pilot study investigated a program of individualized activities designed to
      enhance nocturnal sleep in five cognitively impaired veterans residing in a
      dementia care unit. Actigraphy documented 24-hour sleep-wake patterns of the
      residents for 3 days. Those meeting the criteria for inclusion then participated
      in an Individualized Activity Intervention timed to occur during peak napping
      times for 14 days. During the 10th, 12th, and 14th days of intervention,
      actigraphy provided a repeat measure of sleep-wake patterns. The results
      indicated an increase in nocturnal sleep with increased efficiency, as well as a
      decrease in daytime napping. This pilot study encourages further investigation of
      this potential method for enhancing nocturnal sleep in cognitively impaired
      elderly adults.

PMID- 11820555
TI  - Perceptions of older Latino adults regarding physical fitness, physical activity,
      and exercise.
AB  - Healthy People 2000 has identified the importance of physical activity for
      healthy aging, but little is known about what motivates older individuals, older
      Latino adults, in particular, to be physically active. The purpose of this
      research was to examine the perceptions of older Latino adults toward physical
      fitness, physical activity, and exercise. This study used a qualitative focus
      group design. The sample of Latino adults age 60 and older resided in Northeast
      Massachusetts and was recruited from community settings which serve older Latino
      adults. Three focus groups, consisting of four to eight individuals in each
      group, were conducted and audiotaped. Data analysis used a combination of open,
      axial, and selective coding procedures. Focus group participants viewed physical
      fitness as being able to do anything; the mind and body working together; and
      feeling "light," being healthy. Support was viewed as a motivator of physical
      activity and exercise and included community resources, group support, cultural
      unity, and health provider assistance Barriers of fear and a feeling of
      inappropriateness were identified by focus group participants. Although the study
      was exploratory and the sample size small, it provides useful cultural knowledge
      and information for community health and gerontological nurses. Knowledge about
      older Latino adults' perceptions of motivators and barriers to physical activity
      and exercise is a necessary first step for nurses to prescribe activities that
      will help improve functional independence and quality of life. Nurses can serve
      as links for older Latino adults in accessing community resources. Sociocultural
      factors that influence Latino adult perceptions must be assessed if health
      promotion program planning is to be tailored to meet individual and group needs.

PMID- 11820556
TI  - A review of research on religious and spiritual variables in two primary
      gerontological nursing journals: 1991 to 1997.
AB  - All articles published between 1991 and 1997 in the Journal of Gerontological
      Nursing and Geriatric Nursing were classified as qualitative research,
      quantitative research, or non-research. Of the 784 articles reviewed, 5.1%
      mentioned religion or spirituality. Research articles (7.7%) were more likely
      than non-research articles (2.8%) to address religion and spirituality. No
      statistical difference was found between the percentage of qualitative (10.7%)
      and quantitative (6.8%) studies addressing religious and spiritual factors. The
      percentage of quantitative studies including religious and spiritual variables
      was found to be higher than that found by systematic reviews of the research
      literature in various health professions.

PMID- 11820557
TI  - A key to successful aging: learning-style patterns of older adults.
AB  - A sample of 61 volunteer older adults, age 64 to 88, living independently in a
      suburban, residential senior citizen setting, participated in this dual-pronged
      investigation. It was the first study of its kind to analyze the current and
      previous learning styles of a sample of older adults. Current learning-style
      preferences were assessed through the Productivity Environmental Preference
      Survey (PEPS) and recalled learning-style preferences identified through the
      Previous Learning Experiences Questionnaire. Each older adult participant was
      administered the Short Portable Mental Status Questionnaire to assess their
      cognitive functioning. Two directional research hypotheses were tested. Single
      sample t tests confirmed that these older adults scored significantly different
      on learning-style elements as measured by the PEPS from the original normed
      group. Single-sample t tests also revealed that older adult men were
      significantly different from older adult women on certain learning-style
      preferences. Research conducted with the Dunn and Dunn Learning-Style Model
      during the past 30 years has yielded valuable insights into how learning-style
      preferences evolve over time. This model's research continuum, until recently,
      extended from early childhood through the midlife years of between 40 and 50.
      This investigation currently has expanded the learning-style continuum to
      incorporate octogenarians. The element of perception has provided additional
      information that is important and useful for educators when preparing
      instructional sessions that include diverse older adult participants.

PMID- 11820558
TI  - Expression of vascular endothelial growth factor (VEGF) and its receptor FLK-1 in
      non-small cell lung cancer (NSCLC)--a preliminary report.
AB  - The assessment of tumour angiogenesis in NSCLC is presently a subject of
      intensive research with potential clinical applications. In this study, the
      expression of VEGF and FLK-1 was examined by immunohistochemistry in 67 archival
      tumour samples obtained from NSCLC patients treated by radical resection.
      Distribution of age, sex, tumour stage and histology was typical for patient
      population in Poland. VEGF expression (more than 25% of positive cells) was noted
      in 65% of tumour cells. FLK-1 expression was observed in 91% of tumour cells.
      Neither the number of positive cells nor the staining intensity correlated with
      the clinical variables (all p values >0.05, chi-square test). No correlation was
      noted between the expression of VEGF and FLK-1 (p=0.35, chi-square test). In
      survival analysis, neither the number of positive cells nor the staining
      intensity of both molecules was of prognostic significance. The expression of
      VEGF and FLK-1 in NSCLC cells was confirmed in this study. The relation to
      clinical variables and survival will be further assessed in a larger group of
      patients.

PMID- 11820559
TI  - Evaluation of a system producing the hemopoietic factor. WEHI-3B cell line
      function, when encapsulated in a polypropylene hollow fibre.
AB  - The purpose of our study was evaluation of functioning of WEHI-3B (an mouse cell
      line producing IL-3) cells encapsulated in hollow fibers (HF). In vitro: the WEHI
      3B cells were encapsulated in HF of polypropylene K600 silikonized, and cultured
      over two weeks. In vivo: the encapsulated WEHI-3B after weeks culture, were
      implanted subcutaneously into mice for 1 week. After explantation encapsulated
      WEHI 3-B were cultured again in culture medium for one week. The production of IL
      3 by encapsulated WEHI-3B cells was assessed by evaluation of IL-3 dependent,
      BaF3 cells viability. The percent number of one day survival of BaF3 cells in the
      culture medium supplemented with 15% of encapsulated WEHI-3B in vitro or
      encapsulated WEHI-3B after in vivo conditioned medium was comparable with
      positive control. Possible replacement of recombinant cytokines with HF
      encapsulated cytokine-producing cells may be a chance for continous
      supplementation of the factors for hematopoietic stem cells differentiation.

PMID- 11820560
TI  - Cancer procoagulant as a marker in monitoring the therapy in cases of
      oesophageal, stomach and colorectal cancer.
AB  - Cancer procoagulant activity in the blood serum of patients with oesophagal,
      gastric and colorectal cancer was evaluated before and after the tumour removal.
      Cancer procoagulant activity was significantly higher before the operation in
      comparison to the control group and was reduced after a total operative
      procedure, whereas it was kept on a high level after a non-radical procedure or
      in cases of metastases. Examination results point to the possibility of using the
      evaluation of cancer procoagulant activity in monitoring the course of treatment
      of patients with oesophagal, gastric and colorectal cancer.

PMID- 11820561
TI  - Assessment of the ability of mononuclear blood cells to produce IFN-gamma in
      patients with laryngeal cancer.
AB  - The ability of mononuclear blood cells (PBMC), derived from patients with cancer
      of the larynx, to produce IFN-gamma in vitro was assessed in this paper. Thirty
      patients (27 male, 3 female) were qualified to the study. Their mean age was 65
      (range: 41 to 78 years), tumour sizes found in the group were from T2 to T4,
      levels of pathologic malignancy G2 or G3. The percentage rates different blood
      cells phenotypes (CD3+, CD3+ HLADR+, CD4+, CD8+, CD14+ HLADR+, CD19+, CD56+) were
      evaluated by means of flow cytometry (Coulter EPICS XL). The control group
      consisted of 20 healthy blood donors. PBMC were derived by centrifugation of
      heparinized venous blood on Lymphoprep gradient according to Boyum method. Double
      cell cultures were performed for 24 hours with antibody anti-CD3 or recombinant
      interleukins 12 (rhIL-12) or 18 (rhIL-18). The statistic analysis was based on
      Student t and Mann-Whitney's test with significancy at p<0.05. A significant
      decrease in the production of IFN-gamma by PBMC in patients with laryngeal cancer
      after stimulation with antiCD3 (p=0.018), rhIL-12 (p=0.027), rhIL-18 (p=0.016)
      was found in comparison with the controls. The results suggest a decreased
      production of IFN-gamma in patients with cancer of the larynx.

PMID- 11820562
TI  - Quantitative RT-PCR assay for mRNA of VEGF and histone H4 in the determination of
      proliferative and angiogenic activity in vulvar pathology.
AB  - Proliferative and angiogenic activity of tissue specimens taken from women with
      various vulvar pathologies were evaluated by determining the number of mRNA VEGF
      molecules and H4 histone mRNA molecules, by means of the QRT-PCR (TaqMan)
      technique. Following a cluster analysis the results, where normalised. Euclidean
      distances were used, all the cases were classified into three groups of
      pathologies. Group I included low degree vulvar pathologies, group II included
      high degree vulvar pathologies and group III included vulvar pathologies with
      high proliferative and angiogenic activity. Significant differences were found in
      the proliferative and angiogenic activity between groups I and III, and between
      groups II and III, while no statistically significant differences were found
      between groups I and II.

PMID- 11820563
TI  - Granulocyte-macrophage-colony stimulating factor in patients with colorectal
      cancer.
AB  - Granulocyte-macrophage-colony stimulating factor (GM-CSF) belongs to the group of
      glycoproteins called colony-stimulating factors (CSFs). It has been shown that
      the activity of CSFs is not limited to the hematopoietic cells but can also
      affect the proliferation of colon carcinoma cell lines. The purpose of this
      investigation was to compare the serum level of GM-CSF in colorectal cancer
      patients to a control group, to assess the level of GM-CSF in relation to the
      level of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9),
      and to define the sensitivity, the specificity and the predictive values of GM
      CSF in colorectal cancer. In this study, the serum level of tumour markers was
      measured in 30 patients with colorectal cancer and in 20 healthy subjects. GM-CSF
      was assayed using ELISA system, CEA and CA 19-9 were measured by MEIA. The serum
      levels of CEA, CA 19-9 and GM-CSF were higher in the patients with colorectal
      cancer than in the control group. The sensitivities of CEA (63%) and CA 19-9
      (56%) were lower than the GM-CSF sensitivity (80%). The specificities of tumour
      markers were 70% (CEA, GM-CSF) and 75% for CA 19-9. The GM-CSF predictive v
      values were higher than the CEA and CA 19-9 values. These results suggest that GM
      CSF may be useful as tumour marker in colorectal cancer, but further studies are
      needed.

PMID- 11820564
TI  - Tissue expression of VEGF as a prognostic factor in early cervical squamous cell
      carcinoma.
AB  - The purpose of this retrospective study was to determine whether the intensity of
      tumor angiogenesis, expressed as microvessel density (MD), is indeed an important
      parameter predicting lymph node metastasis and survival rate in 73 women operated
      on for early invasive squamous cell carcinoma of the uterine cervix in stages Ib
      and IIa (FIGO). Angiogenesis was quantified by light microscope (LM) using an
      assay for vascular endothelial growth factor (VEGF). In the study, differences
      were revealed by comparing the MD between both groups. The patient survival with
      high MD was significantly worse than for those with low MD (p<0.01). A
      correlation was found between MD and the incidence of lymph node metastases.
      Hence, quantitative analysis of MD used as the expression of VEGF in the each
      cervical squamous cell carcinomas could be useful as a significant prognostic
      indicator.

PMID- 11820565
TI  - Differentiation strategies of alternative splicing variants mRNA estrogen
      receptor-alpha.
AB  - From the clinical point of view recognizing the concentrations and type profile
      of isoforms could be of significant practical importance. The aim of the study is
      designed QRT-PCR reaction to assess profile of mRNA ER-alpha and their isoforms.
      Theoretical part of the study was made according to computer program and
      available Genbank database. To detect a isoform one of the primer was designed to
      hybridize within exon-border linked in alternative splicing. The study presents
      the differentiation strategies in isoforms coming about as the alternative
      splicing result. Designed oligonucleotide probes and primers allow to distinguish
      mRNA isoforms of ER-alpha and their quantification in assessed tissues.

PMID- 11820566
TI  - Quantitative analysis of estrogen receptor mRNA in human endometrium throughout
      the menstrual cycle using a real-time reverse transcription-polymerase chain
      reaction assay.
AB  - We conducted a quantitative analysis of ERalpha and ERbeta mRNA expression in
      normal human endometrium throughout the menstrual cycle in regular menstruating
      premenopausal women, taking advantage of this real-time PCR assay. Endometrial
      dating was determined from the histology of the endometrium and classified into:
      proliferative endometrium and secretory endometrium. Both ERalpha and ERbeta mRNA
      expression were detected in all endometrial samples at both proliferative and
      secretion phase. However ERalpha mRNA expression level was higher than that of
      ERbeta specially during proliferative phase. These results suggest that
      estrogenic effects occur predominantly through ERalpha than ERbeta.

PMID- 11820567
TI  - Quantitative analysis of estrogen receptor-alpha and -beta and exon 5 splicing
      variant mRNA in endometrial hyperplasia in perimenopausal women.
AB  - We used real-time reverse transcription-polymerase chain reaction (QRT-PCR) to
      detect wild-type ERalpha and ERbeta and their isoforms as well as exon 5 splicing
      variant mRNA ERalpha in various types of endometrial hyperplasia in
      perimenopausal women. Our data suggest that the exon 2 and 7 deletion ERalpha
      mRNA isoforms are present in endometrial tissue undergoing various hyperplastic
      states. Wild type ERbeta mRNA and their isoforms 2, 4, 5, 6 were observed in each
      type of assessed endometrial specimens, and ERalpha/delta5 was found only in
      hyperplasia complex group.

PMID- 11820568
TI  - Carcinogenic risk assessment: some points of interest for a discussion.
AB  - This paper is aimed at providing some elements of discussion about points that
      emerge about the meaning of risk assessment procedures. The considerations that
      will be developed mainly pertain to four topics. First, the feasibility of
      objectively checking the validity of risk assessment results on the basis of
      epidemiological data, particularly for very low exposures. Second, the influence
      of uncertainty factors and the resulting variations in risk estimates. Third, the
      influence of individual susceptibility factors, easily entailing differences in
      risk in the order of three levels of magnitude. These differences, as a
      consequence of genetic factors, are often in the range of three orders of
      negritude and are more evident for low classes of exposure. In the general
      population, DNA repair related susceptibility should also be considered. Fourth,
      the mathematical model of the risk assessment procedure may itself influence the
      results. The default approach adopted by the US EPA is commented.

PMID- 11820569
TI  - Vascular endothelial growth factor and basic fibroblast growth factor in patients
      with squamous cell oesophageal cancer.
AB  - It is suggested that vascular endothelial growth factor (VEGF) and basic
      fibroblast growth factor (bFGF) play an important role in tumor-induced
      angiogenesis. The purpose of this study was to estimate the correlation between
      VEGF and bFGF levels and tumor pathological status according to pTNM
      classification in patients with squamous cell oesophageal cancer. A group of 25
      healthy controls and 32 consecutive patients with oesophageal cancer were
      included in this study. Serum VEGF and bFGF levels were determined by enzyme
      linked immunosorbent assay (Quantikine R&D Systems). Serum VEGF and bFGF levels
      were significantly elevated in the patient groups (VEGF: 146.0 pg/ml, 79.0-386.3
      pg/ml vs. 38.0 pg/ml, 6.5-135.1 pg/ml, p<0.005, and bFGF: 5.2 pg/ml, 1.2-10.6
      pg/ml vs. 2.06 pg/ml, 0.07-4.0 pg/ml, p<0.02 Fisher test). The highest
      correlation between serum VEGF and bFGF levels were found in patients with
      advanced cancers, especially with: T4, N1, and M1 factors. The VEGF and bFGF
      levels were significantly higher in patients with pT4 (p<0.01). Patients with N1
      lymph node invasion, compared with N0 factor, have higher levels of angiogenetic
      factors (p<0.04). Also in patients with advanced cancers with liver metastases
      the serum levels VEGF and bFGF were significantly higher (M1 vs. M0, VEGF p<0.001
      and bFGF p<0.05). Consecutive monitoring of VEGF and bFGF serum levels may be a
      useful prognostic marker for patients with squamous cell oesophageal cancer.

PMID- 11820570
TI  - Endogenous diazepam concentrations in the serum of patients with liver neoplasms.
AB  - The study included 61 patients (35 men and 26 women) ages 47 to 74 in whom a
      primary liver cancer was diagnosed or neoplastic metastases to the liver were
      confirmed in the course of a cancer of the stomach or the large bowel. In each
      patient the endogenous serum diazepam concentration (ESDC) was estimated
      chromatographically and the results obtained were compared to selected clinical
      traits such as the magnitude and number of neoplastic changes and their location
      in the liver parenchyma, the histological form of the tumor and the primary
      location of the cancer in the case of neoplasms of the alimentary canal. The
      determination of the ESDC was also carried out in a control group made up of
      voluntary blood donors. Neither group examined received any medication belonging
      to the benzodiazepine group. From the results of the tests conducted it was
      confirmed that the average ESDC of patients with liver neoplasms was 65 times
      higher than that of the control group. Simultaneously, however, in patients with
      a primary liver cancer the average endogenous concentration was higher than in
      patients with neoplastic metastases to that organ and this was statistically
      significant. The location in the hepatic parenchyma of the neoplastic change as
      well as the primary location of the cancer remained without a statistically
      significant influence in the changes of ESDC. It was moreover shown that
      significantly high ESDC were associated in the liver mainly with increased
      neoplastic growth (above 3 cm in diameter) and with multiple spread (5 focuses
      and more).

PMID- 11820571
TI  - Clinical and morphological analysis of 143 cases of "pulmonary peripheral shades"
      in patients treated in the department of thoracic surgery of Medical Academy in
      Lublin.
AB  - In spite of a constant development of various diagnostic methods, in many cases
      of "peripheral shades" the exploratory opening of the chest appears to be the
      only way leading to a correct diagnosis. In this study, 143 patients were
      examined. These patients were referred to the Thoracic Surgery Department because
      of peripheral shades in the lung areas observed, often accidentally; on regular
      checkup X rays. Our paper assessed the usefulness of endoscopic examinations in
      diagnosing the changes situated peripherally in the lungs. 83.2% of those shades
      were recognized as neoplasms on the basis of histopathological examinations.
      Moreover , we evaluated the concordance of histopathological diagnosis before and
      after the operation.

PMID- 11820572
TI  - Multifocal fibromatosis: a case report.
AB  - We present of rare case of multifocal fibromatosis in a 52 year-old women. In
      1996, she was first evaluated for a tumour of the right breast and on the basis
      of the surgical specimen the extra-abdominal fibromatosis was diagnosed. Four
      years later, she was reevaluated for the tumor of the right lung, and then in
      2001 for the lesion of the right parietal pleura. Microscopic examination of
      pulmonary and pleural lesions revealed histological pattern almost identical with
      the breast tumor. The recurrent lesions were located proximally to the primary
      one.

PMID- 11820573
TI  - Sclerosing stromal tumour--a rare ovarian benign neoplasm: description of three
      cases.
AB  - Sclerosing stromal tumour is a rare benign usually unilateral ovarian tumour. We
      present three cases of this neoplasm in young females, including one bilateral
      case. All tumours were composed of cellular areas forming pseudolobular patterns,
      as well as vascular, fibrous, and myxoid areas. The characteristic feature of
      tumours was cellular heterogenity. All tumours revealed negative immunostaining
      for cytokeratin, and intense positive immunostaining for vimentin, and smooth
      muscle actin. Immunostaining for desmin and progesterone receptors was weakly
      positive.

PMID- 11820574
TI  - Voice creating aspect after horizontal laryngectomy and chordectomy in patients
      with carcinoma of the larynx.
AB  - Voice quality was assessed in 55 patients with the laryngeal carcinoma. A quality
      of voice was examined in 18 patients before and after chordectomy and in 37
      patients before and after supraglottic surgery. Subjective and objective
      spectrography methods were applied to evaluate dysphony. The larynx was examined
      by indirect larngoscopy and videolaryngostroboscopy (VLSS). Significant voice
      pathology was found in patients before surgery when compared with the normal
      group. A change of voice colour was found, which was manifested in spectrography
      by decreased in formant levels, especially F3 and F4 in patients after
      supraglottic surgery. Dysphagia and longer tracheostomy were temporary
      complications after the surgery and resulted in further phoniatric
      rehabilitation. Early phoniatric rehabilitation after chordectomy helped to
      achieve subjective and objective improvement of voice quality in patients after
      surgery. Good voice quality in patients after chordectomy is due to preserved
      structure and increased levels F1, F2, F3, and F4 formants in spectrography.

PMID- 11820575
TI  - Voice analysis after the partial laryngectomy in patients with the larynx
      carcinoma.
AB  - The paper presents 170 cases of patients with the larynx carcinoma after the
      partial laryngectomy. According to the procedure which we used, vertical,
      horizontal and subtotal supraglottis laryngectomies were distinguished. Voice
      pattern was analysed with the use of subjective and objective spectrography. The
      lowest degree of dysphonia was found in patients after the horizontal
      laryngectomy, while the highest degree dysphonia in those after subtotal
      supraglottis laryngectomy.

PMID- 11820576
TI  - Evaluation of the voice function after the supraglottis subtotal laryngectomy.
AB  - Voice quality was analysed in 39 patients with the larynx carcinoma after the
      supraglottis subtotal laryngectomy. Voice pattern was analysed with the use of
      subjective and objective spectrography before and after the surgery. A
      deteriorated voice quality was found after the surgery. The spectrographic
      examination revealed decreased frequency levels of the formants F3 and F4 and the
      presence of a noise component generated in the glottis area.

PMID- 11820577
TI  - Megakaryocytes emperipolesis in bone marrow of the patients with non-Hodgkin's
      lymphoma.
AB  - Emperipolesis of hematopoietic cells within the cytoplasm of the megakaryocytes
      was most often described in association with various pathologic conditions. The
      aim of the research was estimation of the incidence of emperipolesis in the bone
      marrow of the patients with non-Hodgkin's lymphoma (NHL). 30 patients with
      different histological types of NHL (chronic lymphocytic leukaemia--CLL, hairy
      cell leukaemia--HCL, multiple myeloma--MM) in compliance with clinical stage of
      the disease, patient's age and sex were analyzed. Trephine biopsies of the bone
      marrow were carried out in fixative solution and paraffin embedding. Hematoxylin
      and eosin and monoclonal antibody CD 61 were applied on thin sections. Phenomenon
      of megakaryocytic emperipolesis in human bone marrow was found in 6 cases: in 5
      cases in CLL and in 1 case in HCL. In most of them emperipolesis was related to
      single megakaryocytes. We observed in the cytoplasm of the megakaryocytes single
      hematopietic cells-most often lymphocytes, rarely eosinophilic granulocytes. We
      found no correlations between histological types of NHL, clinical stage of the
      disease, patients' age, sex and the incidence of megakaryocytic emperipolesis.

PMID- 11820578
TI  - The coexistence of cystic nephroma and renal cortical adenoma.
AB  - Cystic nephroma is rare, but its coexistence with renal cortical adenoma is
      unique and has never been reported previously. We present a unique case of
      simultaneous occurrence of cystic nephroma and renal cortical adenoma in 47-year
      old man. Both tumours were situated in the lower pole of the right kidney and
      were clinically asymptomatic.

PMID- 11820579
TI  - The conditions favourable to oxidation of Cr (III) to Cr (VI) and the presence of
      chromium forms on the area contaminated by tannery wastes.
AB  - The aim of this paper was to study the conditions favourable to Cr (III)
      oxidation such as: type of soil, soil water content, presence of organic matter
      and three oxidisers (MnO2, NaNO3 and Fe2O3). Also concentrations of different
      species of chromium in water and soils were examined in the area contaminated
      with tannery wastes containing 5-10% of Cr2O3. The action of oxidisers was
      studied in batch experiment for 2 h at room temperature at pH=5.35+/-0.2. The
      highest level of oxidised trivalent chromium was registered for soil with the
      lowest content of organic matter (0.72% C(org)), when Cr (III) was oxidised by
      MnO2, Fe2O3 and NaNO3 did not show properties towards Cr (III) oxidation under
      the conditions described.

PMID- 11820580
TI  - 6-Hydroxydopamine infusions into the structures of mesolimbic dopaminergic system
      alter the memory enhancing effect of CK-8US and caerulein in rats.
AB  - The influence of bilateral destruction of dopaminergic endings in the anterior
      and in the posterior part of nucleus accumbens (NAS) and in the nucleus septi
      lateralis (NSL), by 6-hydroxydopamine (6-OHDA) infusions, on the facilitatory
      effect of cholecystokinin-unsulfated octapeptide (CCK-8US) and caerulein (CER) on
      memory motivated affectively was investigated in male Wistar rats. CCK-8US and
      CER were given s.c. at the doses of 10 microg/kg and 0.5 microg/kg respectively,
      immediately after a single learning trial in a passive avoidance situation, ten
      days after bilateral 6-OHDA lesions (desipramine pre-treatment; 25 mg/kg, i.p.)
      of these structures. Bilateral 6-OHDA lesions to the anterior and to the
      posterior part of NAS totally abolished and significantly attenuated, respective,
      the facilitatory effect of CCK-8US and CER on retention of a passive avoidance
      behaviour evaluated 24 h later, while bilateral lesions to NSL did not have any
      influence on it. Moreover, neither, destruction of dopaminergic endings in
      lesioned structures, nor application of CCK-8US and CER changed the spontaneous
      psychomotor activity of rats estimated in an "open field" test. These results may
      indicate that dopaminergic projection to the anterior part of NAS is mainly
      responsible for the facilitatory effect of CCK-8US and CER on memory motivated
      affectively.

PMID- 11820581
TI  - CD44 glycoprotein as a prognostic factor in laryngeal cancer.
AB  - An association between cell adhesion molecules expression in neoplastic tissues
      and cancer progression has been the focus of many recent studies. In certain
      tumours down-regulation of CD44 expression has been linked to the poor prognosis.
      The aim of the study was to evaluate CD44 expression and to determine the
      correlation between CD44 expression and the clinicopathological features of
      laryngeal cancer. The group consisted of 80 patients with primary laryngeal
      cancer. Tissue samples were taken from removed tumour mass during surgical
      treatment, CD44 expression was assessed by immunohistochemical method. The down
      regulation of CD44 expression significantly correlated with a shorter disease
      free survival (p<0.05). Our results suggest that CD44 expression may be useful as
      a prognostic marker in laryngeal cancer.

PMID- 11820582
TI  - CD44 expression in colorectal cancer. An immunohistochemical study including
      correlation with cathepsin D immunoreactivity and some tumour clinicopathological
      features.
AB  - CD44 is a cell adhesion molecule involved in tumour growth and progression. This
      study was undertaken to evaluate the expression of CD44 standard protein in a
      series of 54 colorectal adenocarcinomas in correlation with cathepsin D
      immunoreactivity and some other clinicopathological variables. Formalin-fixed and
      paraffin-embedded tissues were investigated with anti-CD44 standard protein and
      anti-cathepsin D antibody. Immunolocalisation of CD44 protein and cathepsin D was
      performed using LSAB method. 13 (41.9%) out of 31 carcinomas without lymph-node
      metastases had positive CD44 expression, whereas only 6 (26.1%) out of 23
      carcinomas with lymph-node metastases were found positive for CD44 expression.
      CD44 expression in carcinomas was positively correlated with tumour cells
      cathepsin D (p<0.01) immunostaining. statistically significant correlation was
      found between the expression of CD44 standard protein and the tumour site, age
      and sex of the patients. These results suggest that the standard-type CD44
      protein lymph-node metastases, probably with cooperation of cathepsin D.

PMID- 11820583
TI  - Heavy metals biosorption from aqueous solution by simple eucaryotic organisms.
AB  - Biosorption of cadmium and chromium (III) ions by means of selected yeast species
      has been estimated. Kinetics and equilibrium measurements have shown the reliable
      efficiency of both metals removal for Candida tropicalis. The influence of pH and
      ionic strength on biosorption process has been examined as well. For both metals
      the adsorption isotherms have been presented. The equilibrium of chromium (III)
      sorption has appeared compatible to Langmiur model and the maximum sorption
      capacity has been determined.

PMID- 11820584
TI  - Effect of angiotensin II on protein phosphorylation in PC12 cell line.
AB  - Two subtypes of angiotensin II receptors have been characterised so far: AT1 and
      AT2. In PC12W pheochromocytoma cells, only AT2 receptors have been found (acting
      probably through G1 proteins or via G protein-independent mechanism). Here,
      dynamic changes in phosphorylation pattern in PC12W cells upon induction of
      angiotensin II and under influence of redox agents were investigated. PC12W
      pheochromocytoma cell line was preincubated with angiotensin II, then incubated
      with redox agents. After lysis the cells were subjected to Western-Blotting
      technique with antiphosphotyrosine and anti-ERK2 antibodies, as well as
      phosphotyrosine phosphatases and kinases activity was measured. Angiotensin II
      through its AT2 receptor induced dephosphorylation of tyrosines of the proteins
      in the range of 60 to 150 kD in PC12W cells. The obtained phosphorylation pattern
      suggests that AT2 receptors may act comparably to leukocyte CD45 receptor
      pathway. Treatment of PC12W cells with H2O2 resulted in significant decrease in
      phosphotyrosine phosphatases activity. It could be assumed that signal
      transduction based on protein phosphorylation might be controlled by cellular
      redox mechanisms.

PMID- 11820585
TI  - Cytogenetic assay in apoptosis investigations.
AB  - The mitotic figure, named premature anaphase (PA) or C-anaphase, could be
      considered as a cytogenetic forerunner of following cell apoptosis in G1 phase.
      To confirm this hypothesis the comparative analysis was performed using
      cytogenetic, cytologic, flow cytometric and DNA fragmentation methods upon the
      cells with different proliferative ability and degree of differentiation. PA
      level was significantly increased in bone marrow and blood cells in vitro in
      cases of acute lymphoblastic leukemia and non-Hodgkin lymphoma, decreased until
      total disappearance in remission and not revealed in control. Particularly high
      PA level was registered in embryonal liver's haemopoetic stem cells ex vivo. Flow
      cytometry measurements showed appearance of additional sub-G1 peak of apoptotic
      DNA loss both in leukaemic and embryonal cells, whereas DNA-ladder phenomenon was
      revealed just only in embryonal samples in vivo. Significant positive correlation
      between the frequency of cells with apoptotic DNA loss and PA level on the
      chromosomal preparations was registered. Thus, premature anaphase phenomenon is
      considered as non-random event, associated with high risk of following cell
      death.

PMID- 11820586
TI  - Proliferating activity, DNA ploidy changes of lung cancer cells before and after
      chemotherapy.
AB  - To assess proliferating activity, DNA ploidy changes of lung cancer cells before
      and after chemotherapy, we performed a flow cytometry analysis (FC) using fresh
      bronchoscopy specimens from 38 patients with lung cancer. Among 33 males and 5
      females, squamous cell carcinoma (NSLC) was recognized in 12 males, 15 males had
      small cell lung cancer (SCLC) and 6 males had lung cancer with no histological
      type (LC) defined. Three women had SCLC, 1 had NSCLC and one had LC. Control
      consisted of 11 COPD patients. The percentage of diploid cells was significantly
      lower and cells with hypoploid cells were significantly higher in study group
      before treatment. High percentage of G2M cells characterised NSCLC and LC groups,
      whether high number of S phase cells characterised NSCLC and SCLC group before
      treatment. The treatment lowered percentage of G2M cells in NSCLC and CA group,
      whether diploid, hypoploid and S phase cells did not differ than those from
      before treatment.

PMID- 11820587
TI  - The genetic background of medullary thyroid carcinoma in young patients.
AB  - The study was undertaken to evaluate the frequency of RET polymorphisms at codons
      769 and 836 in young medullary thyroid carcinoma (MTC) patients in whom the
      presence of a known germline mutation has been excluded. 40 patients aged 10-29
      were subjected to genetic analysis of RET exons 10, 11, 13, 14 and 16 and
      compared to 140 older patients. The hereditary component occurred to be very high
      in young MTC patients: 57% carry the germline mutation, other 28% exhibit at
      least one rare polymorphic variant of RET. The observed allelic frequencies were
      38% for polymorphic variant L769CTG and 6% for variant S836AGT. The results were
      significantly higher than those obtained in the group of older patients: 20% and
      1% for L769CTG and S836AGT, respectively. Our results speak in favour that the
      polymorphism in RET codon 769 and 836 may also be a factor predisposing to the
      development of MTC in young age.

PMID- 11820588
TI  - Thyroid dysfunction and aneuploidy in offspring.
AB  - The intercommunication between thyroid gland dysfunction in parents and aneuploid
      karyotype formation in offspring was studied using cytogenetic and immunogenetic
      approaches. It was determined, that increased risk for children being born with
      Down or Turner diseases depends upon a presence of following HLA-antigenes in
      parents, partcularly in motheritract. The intercommunication between thyroid
      gland dysfunction in parents and aneuploid karyotype formation in offspring was
      studied using cytogenetic and immunogenetic approaches. It was determined, that
      increased risk for children being born with Down or Turner diseases depends upon
      a presence of following HLA-antigenes in parents, particularly in mother's
      genome: B10, B40, B41, B51 and allele DQA*0301 of gene DQA of major
      histocompatibility complex. The presence of antigens B40, B51 and allele DQA*0301
      was also associated with autoimmune thyroiditis. Thus, thyroid gland function
      disturbance, namely autoimmune thyroiditis can be considered as a risk factor of
      aneuploid karyotype formation.

PMID- 11820589
TI  - p53, MDM2, bcl-2 staining in follicular neoplasms of the thyroid gland.
AB  - Sixty-two follicular adenomas of the thyroid were investigated by
      immunohistochemistry for the expression of p53, MDM2 and bcl-2 proteins. The wild
      type of 393 aminoacid nuclear p53 phosphoprotein is the product of a gene located
      on the short arm of chromosome 17. The p53 protein controls the growth of
      transformed cells in a culture and thus termed a suppressor gene product. Mouse
      double minute 2 (MDM2) gene product has been described to occur in malignant
      epithelial tissue, the protein product of this gene binds to and presumably
      inactivates the growth suppressive effect of wild type p53 protein. Bcl-2 is an
      oncogene whose product inhibits apoptosis in many cells types. Some scattered
      nuclei in two adenomas (3.2%) stained positively for p53. The adenomas with
      positive staining for p53 were subserially sectioned, but no signs of invasion
      were found, both patients are alive and well. In 12 adenomas (19%) there was
      positive reaction for MDM2 protein, whereas none of them where p53 positive. All
      cases were strongly positive for bcl-2 staining. We conclude that p53 protein
      expression is not confined to follicular adenomas, while MDM2 and bcl-2 genes
      products are.

PMID- 11820590
TI  - Quantification of P21 mRNA in biopsy specimens of colon tissue at different
      stages of neoplastic transformation.
AB  - Induction of the P21 protein is an integral part of cell growth arrest associated
      with the cellular response to senescence or damage. Changes in the P21 protein
      level are often observed in tumour cells and it is suggested, that they correlate
      with malignancy. We studied the P21 gene expression at the mRNA level in biopsy
      specimens from colitis ulcerosa, adenomas and adenocarcinomas using TaqMan assay.
      Our results showed, that quantity of the P21 transcript was evidently lower in
      the cases with adenocarcinomas than in the cases with colitis ulcerosa or
      adenomas.

PMID- 11820591
TI  - Risk analysis: an overview.
AB  - Risk analysis increasingly is considered as an integral part of the environmental
      management decision-making process. Risk, defined as the probability of
      occurrence of a particular adverse effect on human health or the environment,
      should not be confounded with hazard, defined as a source of potential injury
      independent of occurrence. Risk analysis has to be followed by risk management.
      Some opponents of risk analysis make the reproach that the science used in risk
      analysis is immature and consequently that the entire process in laden with
      hidden value judgments. Attempts to overcome these critics are increasingly based
      on the use of robust biologic data the final considered values system being
      efficacy-based, efficiency-based or equity-based. Globalization has brought with
      it new problems, and there is an urgent need to improve risk analysts; to
      increase its public acceptability and to establish consensus regarding solutions
      to global environmental problems. In this context biologic-based models and
      biomarkers hold, the greatest promise for improving risk assessment. These
      considerations are illustrated by a few examples, also pertaining to low-dose
      extrapolation and to the problem of thresholds for carcinogenesis. Future
      directions for development are evoked.

PMID- 11820592
TI  - Tumour budding intensity in relation to cathepsin D expression and some
      clinicopathological features of colorectal cancer.
AB  - Although it has been suggested that tumour budding at the invasive edge of
      colorectal cancer is an important prognostic factor its biological significance
      for tumour progression is still to be evaluated. The aim of the study was to
      correlate tumour budding intensity with cathepsin D expression and some other
      clinicopathological variables of presumed or established prognostic value. 48
      patients with colorectal cancer at pT3 stage, G2 grade of histological
      differentiation and tumour budding at the invasive edge were evaluated.
      Colorectal tumours were investigated for cathepsin D expression by
      immunohistochemistry of formalin-fixed and paraffin embedded tissues. There was
      no statistically significant relationships between tumour budding intensity grade
      and primary tumour cathepsin D expression, stromal cell cathepsin D expression
      and histochemical immunostaining of cathepsin D in rumour budding at its invasive
      edge. The tumour budding intensity was not associated with lymph node status,
      tumour site, peritumoral inflammatory response as well as the patient's age and
      sex. The results of this study suggest that intensity of tumour budds formation
      at the invasive margin of colorectal cancer is not associated with presumed or
      established prognostic factors such as lymph node metastases, and peritumoural
      inflammatory reaction as well as cathepsin D expression.

PMID- 11820593
TI  - Circulating anti-p53 antibodies in esophageal cancer patients.
AB  - Circulating anti-p53 protein antibodies (p53-Abs) have been detected in some
      cancer patients. The aim of the study was to determine the presence of
      circulating anti-p53 protein antibodies and their clinical significance in
      patients with esophageal carcinoma. Serum specimens from 75 consecutive patients
      with squamous cell carcinomas and 10 healthy subjects were studied. Enzyme linked
      immunosorbent assay (ELISA--Pharma Cell) was used to detect p53-Abs. At the time
      of diagnosis 20 (26.6%) of 75 analyzed patients had positive result in the p53
      Abs test, but not any of the healthy subjects. The positive rate was 25% (1/4)
      cases in stage I, 41% (10/24) cases in stage IIA, 0% (0/8) cases in stage IIB,
      28% (8/28) cases in stage III and 9% (1/11) cases in stage IV. In respect of
      tumour differentiation, cases graded as G1, G2 and G3 were positive in 28.5%
      (4/14), 25.9% (7/27) and 26.4% (9/34), respectively. There was no correlation
      between presence of p53-Abs and stage, rumour differentiation, lymph nodes
      metastases, tumour size, patient age and sex. In conclusion, the results of the
      present study indicate that serum p53-Abs did not correlate with
      cliniocopathologic feature of esophageal carcinoma.

PMID- 11820594
TI  - Expression of p21 and bcl-2 proteins and p53 mRNA in surgically resected
      preparations of non-small cell lung cancer (stage IIIA) after etoposide and
      cisplatin chemotherapy.
AB  - Apoptosis which is also a called programmed cell death plays an important role
      during development, homeostasis and in many diseases such as cancer. Apoptosis is
      a genetically encoded cell death program defined by characteristic morphological
      and biochemical features. It is well recognized as a distinct pathologic
      mechanism in tumours responding to anticancer therapies. Many genes play an
      important role in this process. We evaluated an expression of the tumour
      supressor gene p53 and proteins p21 and bcl-2 in non-small cell lung cancer. We
      examined resected tumour tissues from 30 patients who received neoadjuvant
      chemotherapy. As a control we assessed tissues from patients treated without
      chemotherapy. Histological slides of the resected tumours were evaluated by
      TUNEL, in situ hybridisation and with immunoperoxidase staining procedure. The
      results were documented by photography. We examined the level of extinction using
      cytophotometry. In conclusion, preoperative chemotherapy induces apoptosis in
      cancer cells. The level of p53 correlates with the acceleration of TUNEL
      reaction. The loss of bcl-2 expression correlated with an increased apoptotic
      cell death. There was an increased p21 protein expression in the examined cancer
      tissues after chemotherapy.

PMID- 11820595
TI  - Photofrin--factor of photodynamic therapy induces apoptosis and necrosis.
AB  - Photodynamic therapy (PDT) causes irreversible photodamage of tumor and other
      malignant tissues. The effect of reactive oxygen species generation in the
      presence of photofrin (HpD) was studied. The studies were performed on
      endothelial cell line from foetal aorta of calves and on normal fibroblasts cell
      line (3T3 -Balb) and also on malignant line (A431). The cells were grown in
      presence of photofrin at different time intervals. Time of interaction of
      photosensitiser with cells was very important. Short time of exposure of the
      cells to photofrin induced mostly apoptosis in normal cells and apoptotic or
      necrotic changes in malignant cells. Longer effect of these factors on cells
      provoked necrosis. The factors of PDT influence dynamic changes of SOD and CT
      activity. It was dependent on the intensity of factors. These results strongly
      suggest that HpD has an effect on generation of ROS, which are a signal for
      development of morphological changes (apoptosis or necrosis) in normal and
      malignant cells.

PMID- 11820596
TI  - BCL2 and BAX mRNA concentration profile in fibrillary astrocytoma.
AB  - A high level of the BCL2 protein and the lack of apoptosis promoting protein BAX
      are beginning to be treated as markers of cellular resistance to anti-neoplastic
      drugs. The object of the study were specimens from stereotactic biopsy of
      Astrocytoma fibrillare in the central brain area, inaccessible to conventional
      surgery. The cytological preparations have been evaluated with histopathological
      and immunohistochemical methods in order to determine the origin of the tumour
      and assess cell proliferation activity. The molecular analysis conducted in order
      to determine the sensitivity of the tumour to radio- or chemotherapy included the
      determination of the number of mRNA BCL2 alpha and beta molecules and of BAX in 1
      microg total RNA obtained from microscope slides. A higher expression of BAX than
      of BCL2-alpha is a prognosis for a positive result of chemo- or radiotherapy. A
      trace number of mRNA BCL2-beta molecules and a smaller number of mRNA BCL2-alpha
      molecules than mRNA BAX is a good prognosis for therapy.

PMID- 11820597
TI  - Concentration profile of mRNA of kinine B1 and B2 receptors in the evaluation of
      colon pathologies.
AB  - Colon pathologies involve the activation of a number of inflammation mediators:
      cytokines, prostanoids and kinines. The expression patterns of the genes
      associated with their activation may provide a very sensitive marker of the
      physiological condition of the cells. This paper demonstrates certain
      statistically significant differences (p = 0.008) between the expression patterns
      of kinine B1 and B2 receptor encoding genes for colitis ulcerosa and a control
      group. The ratio of kinine B1/B2 concentrations changes significantly, on the
      average from 1.3 for a tissue assessed as healthy to 6.6 for colitis ulcerosa.

PMID- 11820598
TI  - Expression of telomerase genes as potential marker of neoplastic changes.
AB  - We conducted a quantitative analysis of TERT, TP1 and hTR mRNA expression in
      various types of endometrial hyperplasia in perimenopausal women, taking
      advantage of the real-time PCR assay. All women underwent hysterectomy for
      gynecological reasons. Endometrial dating was determined from the patomorphology
      of the endometrium and classified into endometrial hyperplasia: simplex, complex
      and atypica. Our data suggest that only hTR was observed in each normal and
      hyperplastic endometrium specimens, suggesting that this factor constitutively
      expressed in endometrium. The results obtained indicate that the expression
      activity of the TERT subunit changes but not significantly, depending on the
      stage of development of the hyperplasia.

PMID- 11820599
TI  - The clinical significance of serum soluble interleukin 2 receptor (sIL-2R)
      concentration in lung cancer.
AB  - The activated mononuclear cells can release a soluble form of interleukin 2
      receptor (sIL-2R) in the blood. Serum sIL-2R level is a sensitive and
      quantitative marker of circulating peripheral blood mononuclear cell activation.
      This molecule acts as an antagonist of IL-2-mediated responses. The present study
      was carried out to analyze the circulating levels of sIL-2R in lung cancer in
      relation to the histological type of the tumour, clinical stage, response to
      therapy, time survival for patients. The study included 62 patients (30 SCLC, 32
      NSCLC) and 10 healthy subjects as controls. SIL-2R serum levels were measured
      with a sandwich enzyme immunoassay using commercial kits (ENDOGEN). The mean
      serum values of sIL-2R were significantly higher in cancer patients than in
      controls (p=0.01). There was no significant difference in relation to tumour
      histological type. Within the NSCLC chemotherapy group, sIL-2R mean levels
      observed at the end of chemotherapy were higher in the progressing patients than
      in the responding patients. The metastatic patients had higher levels of sIL-2R
      than those with locally limited disease. In the case of SCLC classified to
      extensive disease mean levels of sIL-2R were higher than SCLC classified to
      limited disease. The mean serum values of sIL-2R were significantly higher in
      weight loss patients than no weight ones (p=0.03). Within NSCLC group there was a
      correlation between sIL-2R mean levels and the age of patients (p=0.04). In SCLC
      group there was a correlation between levels of sIL-2R and time survival for
      patients (p=0.009).

PMID- 11820600
TI  - Expression of the histone H3 gene in the evaluation of cellular proliferation in
      colitis ulcerosa.
AB  - A comparison of the number of mRNA molecules of histone H3 in 1 microg total RNA
      extracted from colon sections sampled during colonoscopy was used to evaluate
      cellular proliferation activity in the rectum and sigmoid, in normal tissue and
      in colitis ulcerosa. Samples with similar intensity of the disease were selected
      for the study. Statistically significant differences between both groups of
      rectal sections were found in the expression of histone H3 encoding genes. The
      statistically significant result (p = 0.0485) indicates a more active division of
      cells in the healthy rectum, with no statistically significant differences in the
      sigmoid (p=0.9575).

PMID- 11820601
TI  - Detection of human papillomavirus in papillomas of oral cavity.
AB  - The oral cavity is exposed to many harmful factors among others: tobacco, alcohol
      and viral infection e.g. human papillomaviruses (HPV). HPV belongs to a family of
      tumorigenic viruses and induces cutaneous and mucosal proliferations of
      epithelial cells. The aim of our study was to estimate the frequency of HPV
      occurrence in papillomas of oral cavity in the Podlasie region. The study
      included 38 papillomas of oral cavity. HPV was found in 14 cases (36.8%). High
      risk HPV was present in 12 papillomas, while low risk HPV was detected in 2
      papillomas.

PMID- 11820602
TI  - Proliferating activity in oral dysplastic leasions and squamous cell carcinomas.
AB  - The aim of the study was the quantitative analysis of AgNORs in oral squamous
      cell carcinomas as well as in dysplastic epithelial changes accompanied and not
      accompanied by oral squamous cell carcinomas. AgNOR proteins were visualized in
      histological slides using silver impregnation technique according to D. Ploton.
      In each sample 100 cell nuclei were assessed. The study used 54 cases of
      proliferating oral epithelial changes divided into 3 groups: group I consisting
      of 13 cases of dysplastic lesions not accompanied by oral squamous cell
      carcinomas; group II (a total of 18 cases) containing dysplastic lesions situated
      in the vicinity of oral carcinomas and group III (23 cases) with oral squamous
      cell carcinomas. Statistically significant differences were found between groups
      with mild dysplasia and groups with severe dysplasia as well as squamous cell
      carcinomas. Statistical analysis did not show any differences in the number of
      AgNORs between squamous cell carcinomas and epithelial lesions with severe
      dysplasia. Our results demonstrate that the analysis of AgNORs expression can
      serve only as an additional parameter to evaluate the potential of malignant
      transformation.

PMID- 11820603
TI  - PCNA and P53 expression in relation to clinicopathological features of oral
      papilloma.
AB  - Although papilloma is the most frequent benign epithelial tumour of oral cavity,
      its biological potential for malignant transformation is still to be evaluated.
      The aim of the study was to correlate PCNA and P53 expression in 55 oral
      papillomas with some clinicopathological variables. The tissue samples were
      stained with H+E and by immunohistochemistry for PCNA and P53 protein. Staining
      patterns were assessed semiquantitatively and correlated with each other and
      grade of tumour epithelial dysplasia, tumour size, localization well patient age
      and sex. PCNA immunostaining was positive 43 (78%) oral papillomas. P53
      immunohistochemical reaction was positive in 38 (69%) out of 55 epithelial
      tumours. Positive relationship between PCNA and P53 expression was observed as
      well as between PCNA immunostaining and grade of epithelial dysplasia. There was
      no statistically significant relationships between PCNA, P53 immunohistochemical
      positivity and papilloma size, site, patient age and sex. The results of this
      study suggest that immunohistochemical P53 overexpression is valuable marker of
      early neoplastic transformation and together with PCNA are presumed predictors
      for malignant transformation of oral papillomas.

PMID- 11820604
TI  - Patterns of immunohistochemical staining for p53 expression in hyperplastic
      endometrium and adenocarcinoma.
AB  - The p53, a tumour suppressor gene, is the most commonly mutated gene human
      cancer. In this study, we performed immunohistochemical investigations of the
      expression of p53 protein in hyperplastic endometrium and adenocarcinoma.
      Positive immunostaining was detected in 7 (30%) cases of invasive adenocarcinoma,
      2 (12%) cases of simple hyperplasia with atypia and 2 (14%) cases of complex
      hyperplasia with atypia. In simple and complex hyperplasia without atypia
      staining was seen in occasional cells. The results suggested that endometrial
      hyperplasia is not always accompanied by p53 protein accumulation, hence its
      expression is not an early exponent of the neoplastic process.

PMID- 11820605
TI  - Study of p53 protein expression in prostate cancer.
AB  - The aim of this study was the immunohistochemical evaluation of p53 protein
      expression in localized prostate cancer (Pca) following radical prostatectomy and
      analysis of its relationship to chosen anatomo-clinical and morphological
      parameters of the tumours. The present investigation included material from 28
      randomly selected patients undergoing radical prostatectomy. Tissue sections were
      fixed in 10% buffered formaldehyde solution, embedded in paraffin and stained
      immunohistochemically with the anti-human p53 protein monoclonal antibody. The
      immunolocalization of p53 protein was performed using the Labelled Streptavidyn
      Biotin (LSAB) method. The p53 protein expression was semiquantitatively assessed
      in neoplastic cells and the reaction present in more then 25% of tumour cells was
      accepted as the threshold of positivity. No correlation was found between p53
      protein expression and Gleason score, pT stage, lymph node metastases, seminal
      vesicles invasion, positive or negative surgical resection margins, age of
      patients. However, p53 protein expression and capsular penetration was found
      statistically significantly correlated.

PMID- 11820606
TI  - Effect of the cytokine rhTNF-alpha on the population of mast cells in the growth
      of MethA fibrosarcoma--a TEM study.
AB  - The aim of the present study was the ultrastructural characteristics of mast cell
      (MC) involved in host antitumor responses induced by local (i.t.) administration
      of recombinant human tumor necrosis factor alpha (rhTNF-alpha) in the primary
      focus of methA fibrosarcoma. MC were involved in tumor interstitium remodeling.
      Numerous mitochondria, well-developed RER and Golgi apparatus, clusters of
      polyribosomes, considerable polymorphism of granules and differentiated lamellar
      structures which frequently presented myelinic forms were observed after rhTNF
      alpha application. In the study numerous fibres of the fibrous tissue, richly
      vascularized, occurred in the peripheral and intermediate tumor zones. Cluster of
      MC and tumor cells were seen on the border of the necrotic foci. However,
      proteolytic enzymes released by MC cause interstitial lysis, ensuring the place
      for tumor growth, and are involved in angiogenesis. Thus, it is not clear whether
      MC contribute to the inhibition of tumor growth or have an adjunctive role in
      tumor progression.

PMID- 11820607
TI  - Assessment of endocrine disruptors: approaches, issues, and uncertainties.
AB  - This paper focuses on the quantitative risk assessment of environmental endocrine
      disrupting chemicals (EDCs) to human health. An EDC can be defined as an
      exogenous agent that interferes with the normal endocrine signaling and
      communication mechanisms. The normal feedback control system of natural hormones
      is responsible for regulatory mechanisms that maintain homeostasis. Hormones
      deliver their message to target cells by interacting with receptors, initiating
      signal transduction, gene transcription, and mRNA translation, and ultimately
      leading to cellular response. Because effects of EDCs include diverse disease
      endpoints such as cancer, reproductive toxicity, developmental toxicity, immune
      system effects, acute toxicity, and neurotoxicity, risk assessment of EDCs is
      necessarily endpoint-specific. From the quantitative viewpoint, it is best to
      model the normal endocrinology and then extend the model to include impacts
      attributable to a particular exogenous agent. A practical approach to such a
      complex process is to break the spectrum of biochemical and biological events
      into modular components: e.g., pharmacokinetics, biochemical/molecular (including
      cellular signaling), and cellular response/dynamics. A flexible mathematical
      procedure that is capable of modeling each of these components is suggested.
      However, a real biologically based model is not yet feasible because of a lack of
      necessary biological information. A challenge to risk assessors is how to develop
      a hybrid risk assessment approach that can use the limited biological information
      available for a specific agent and avoid relying on a default approach that
      incorporates no biological information. The USEPA's default approach is to derive
      benchmark dose (BMD) or benchmark concentration (BMC) on the basis of a
      predetermined empirical dose-response model. BMD (or BMC) is the highest dose (or
      concentration and duration) of exposure that is considered unlikely to cause
      adverse effects in a human population, including sensitive subgroups. Data from
      two studies are used to stimulate discussion of issues and the needs for new
      quantitative approaches and data for assessing endocrine disruptors. Statistical
      concepts about threshold effect and the U-shaped dose-response relationship are
      also discussed. This report is a condensed version of the one to be published in
      the monograph of the NATO Advanced Research Workshop, Endocrine Disrupters and
      Carcinogenesis Risk Assessment" held May 8-12, 2001, in Bialystok, Poland.

PMID- 11820608
TI  - Expression of proteins: D1 cyclin and Ki-67 in papillary thyroid carcinomas.
AB  - The aim of the study was an evaluation of expression of D1 cyclin and Ki-67
      proteins in tissue of human papillary thyroid carcinoma (PTC) in a group of
      papillary microcarcinomas and in a group of PTC with a degree of staging higher
      than pT1a in TNM classification. We performed immunohistochemical staining and
      found no statistical differences between groups. These results suggest that
      changes of expression of D1 cyclin are an early event in tumorigenesis.

PMID- 11820609
TI  - Proliferative activity of the thyroid oxyphilic tumor cells estimated by means of
      quantitative analysis of silver stained nucleolar organizer regions (AgNORs).
AB  - Promising results of studies on different neoplasms, by means of morphometric
      analysis of argyrophilic nucleolar organizer regions (AgNORs), known as
      proliferative activity marker, made us undertake an attempt to evaluate of
      proliferative activity in Hurthle Cell Tumors using the same technique. 78 cases
      including 20 Hurthle Cell Carcinomas (HCC), 32 Hurthle Cell Adenomas (HCA) and 26
      hyperplastic nodules with Hurthle Cell Metaplasia (HCM), diagnosed in the
      Department of Clinical Pathology, Medical Academy of Bialystok in the years 1990
      2000, were subjected to analysis. For visualization of the NORs we used the D.
      Ploton et al. technique. Mean AgNOR count and NORDS (NOR distribution score--the
      percentage of nuclei with at least 5 argyrophilic granules) were estimated in
      each case in 100 randomly chosen nuclei. Non-parametric Mann-Whitney U-test was
      applied to determine statistically significant differences. RESULTS: Mean AgNoRs
      counts and NORDS values were 5.1 and 52%, 3.4 and 26%, 2.5 and 7% in HCC, HCA and
      HCM respectively. Statistically significant differences were found between AgNORs
      counts in carcinomas and adenomas (p<0.01), HCCs and HCMs (p<0.005) and betwveen
      NORDS in all groups (p<0.001).

PMID- 11820610
TI  - MIB-I as a proliferative activity marker of the multiform glioblastomas.
AB  - MIB-I is a proliferative activity marker of multiform glioblastomas which are the
      most frequent tumors of the central nervous system. They are characterizad by
      differential rate and prognosis. The aim of the study was to determine the
      proliferative activity of multiform glioblastomas and estimation of the
      correlation between tumors' proliferative activity and tumors' localization,
      size, patients' age and sex. 24 patients (18 females and 6 males) with multiform
      glioblastomas were analyzed. The mean patients' age was 52.1. The proliferative
      activity was calculated as a proliferation index: IP for MIB-I. Cells with
      positive reaction were determined by MIB-I which was compared to all neoplastic
      cells. The most frequent localization of the tumors were frontal and temporal
      lobes of the brain. The size of the tumors ranged from 2.5 to 5.3 cm (mean 3.9).
      Mean IP was 43.2 (SD+/-17.4). We found no correlation between IP MIB-I and
      localization of the tumor, patients' age and sex. There was a marginal
      statistically significant correlation between IP MIB-I and size of the tumor
      (p=0.005).

PMID- 11820611
TI  - Cytotoxicity activity of L-proline analogues of anthraquinone-2-carboxylic acid
      in breast cancer MCF-7 cells.
AB  - Although prolidase [E.C.3.4.13.9] is found in normal cells, substantially
      increased levels are found in some neoplastic tissues. Prolidase evokes the
      ability to hydrolyse the imido-bond of various low molecular weight compounds
      coupled to L-proline. The synthesis of three proline analogues of anthraquinone-2
      carboxylic acid (1-3) has been performed. Treatment of these prodrugs with
      prolidase generated L-proline and the free drug, demonstrating their substrate
      susceptibility prolidase. The concentrations of 1, 2 and 3 needed to inhibit
      [1H]thymidine incorporation into DNA by 50% (IC50) in breast cancer MCF-7 cells
      were found to be 185 +/- 5 microM, 107 +/- 6 microM and 87 +/- 6 microM,
      respectively, suggesting a lower cytotoxic potency of these compounds compared to
      Hoechst 33228 (IC50 = 55 +/- 6 microM).

PMID- 11820612
TI  - Proline analogue of melphalan as a prolidase-convertible pro-drug in breast
      cancer MCF-7 cells.
AB  - Prolidase [E.C.3.4.13.9] is ubiquitously distributed cytosolic egzopeptidase that
      is known to cleave imido-bond of some low molecular weight compounds coupled to L
      proline. Previously we have found that conjugation of antineoplastic drug-
      melphalan (Mel) with proline (pro) through imido-bond resulted in formation of a
      good substrate for purified prolidase. Cytosolic location of prolidase in
      neoplastic cells suggests that proline analogue of melphalan (Mel-pro) may serve
      as a prolidase convertable pro-drug. We have compared several aspects of
      pharmacologic actions of Mel and Mel-pro in breast cancer MCF-7 cells. It has
      been found that Mel-pro is more effectively transported into the MCF-7 cells,
      evokes higher cytotoxicity, lower antimitotic activity and collagen-inhibiting
      activity, compared to Mel. The results suggest that targeting of prolidase as a
      pro-drug-converting enzyme may serve as a potential strategy in pharmacotherapy
      of breast cancer.

PMID- 11820613
TI  - FAK-independent regulation of prolidase activity and collagen biosynthesis in MCF
      7 cells.
AB  - Prolidase [E.C. 3.4.13.9] plays an important role in the recycling of proline for
      collagen synthesis and cell growth and this enzyme activity determines the rate
      of collagen turnover. It has been previously suggested that prolidase activity is
      regulated through signal mediated by the interaction of ECM proteins, with b1
      integrin receptor and that this interaction is disturbed in MCF-7 cells. The
      potential candidates for mediating signal transduction are the nonreceptor
      tyrosine kinase p125FAK and two mitogen-activated protein (MAP) kinases, ERK-1
      and ERK-2, which are activated upon attachment of cells to ECM. We found that
      serum starvation of MCF-7 cells for 24 hours contributed to a significant
      decrease (by about 30%) in prolidase activity and collagen biosynthesis. These
      phenomena were accompanied by suppression of MAP kinases expression without any
      effect on the expression of FAK. The data suggest that prolidase activity and
      collagen biosynthesis respond to signal mediated by MAP kinases, independently of
      FAK expression in MCF-7 cells.

PMID- 11820615
TI  - Molecular changes in thyroid neoplasia.
AB  - All authors integrating the known facts into a model of thyroid carcinogenesis
      concur that two main histotypes of thyroid cancer exhibit different routes of
      molecular development. RET rearrangements are an initiating event in papillary
      carcinoma, and simultaneously the most characteristic mutation for this type of
      cancer. They are followed by further, not well recognized, mutations. RAS
      mutations are regarded as a crucial event in the development of follicular tumors
      already at the adenoma step, while in papillary cancer they belong to the
      spectrum of secondary mutations, enabling tumor progression. Aberrant DNA
      methylation, causing loss of P16 tumor supressor gene, may be a common event in
      both types of cancer. Aneuploidy is seen much more frequently in follicular than
      in papillary cancer, which also exhibits a low rate for loss of heterozygosity
      and microsatellite instability. Mutations of the P53 tumor supressor gene are a
      common feature of undifferentiated thyroid cancers and could be responsible for
      their aggressive phenotype. RET rearrangements have been proposed as identifying
      fingerprints for irradiation induced thyroid cancer in children. Our own data
      speak against this hypothesis. We noted a high frequency of RET/PTC3 mutations in
      a group of Polish children with papillary thyroid carcinoma, regarded as sporadic
      cancer.

PMID- 11820614
TI  - Human exposure to endocrine disrupters: carcinogenic risk assessment.
AB  - Human exposure to endocrine disrupters (EDs) is widespread and is considered to
      pose a growing threat to human health. Recent advances in molecular and genetic
      research and better understanding of mechanisms of blastic cell transformation
      have led to efforts to improve cancer risk assessment for populations exposed to
      this family of xenobiotics. In risk assessment, low dose extrapolation of cancer
      incidence data from both experimental animals and epidemiology studies has been
      largely based on models assuming linear correlation at low doses, despite
      existence of evidence showing otherwise. Another weakness of ED risk assessment
      is poor exposure data in ecological studies. Those are frequently rough estimates
      derived from contaminated items of local food basket surveys. Polyhalogenated
      hydrocarbons are treated as examples. There is growing sense of urgency to
      develop a biologically based dose response model of cancer risk, integrating
      emerging data from molecular biology and epidemiology to provide more realistic
      data for risk assessors, public, public health managers and environmental issues
      administrators.

PMID- 11820616
TI  - Hormonal and hormone-like effects eliciting hepatocarcinogenesis.
AB  - In various species, the manifestation of hepatocellular neoplasms is regularly
      preceded by preneoplastic foci of altered hepatocytes (FAH), the cellular
      phenotype of which is strikingly similar in experimental and human
      hepatocarcinogenesis, irrespective of the etiology of this process. The different
      types of FAH have been related to three main preneoplastic hepatocellular
      lineages: 1) the glycogenotic-basophilic cell lineage, 2) its xenomorphic-tigroid
      cell variant, and 3) the amphophilic-basophilic cell lineage. The predominant
      glycogenotic-basophilic and tigroid cell lineages developed especially after
      exposure to DNA-reactive chemicals, radiation, viruses, transgenic oncogenes and
      local hyperinsulinism. The early phenotypes of these lineages indicate an
      initiation by insulin or insulinomimetic effects of the oncogenic agents,
      triggering the raf-Map kinase signal transduction pathway. In contrast, the
      amphophilic-basophilic cell lineage has mainly been observed after exposure of
      rodents to not directly DNA-reactive peroxisome proliferators but also
      hepadnaviridae, its biochemical pattern mimiking an effect of thyroid hormone.

PMID- 11820617
TI  - Detection of p16 abnormalities in early-stage non-small cell lung cancer.
AB  - We investigated the clinical significance of p16 abnormalities (mutations by
      sequencing and hypermethylation by methylation-specific PCR) in 52 radically
      resected stage I-II non-small cell lung cancers (NSCLCs). P16 abnormalities were
      detected in 20 (38%) patents (point mutations in 4 (8%) and promoter
      hypermethylation in 16 (31%) cases. No correlation was found between p16
      abnormalities and various clinicopathologic factors, including sex, histological
      type of tumor and TNM (I vs. II) stage. The multivariate analysis of survival was
      performed using the Cox proportional hazard model. When the types of 16
      inactivation were analyzed, p16 hypermethylation rather than point mutation was
      associated with poor Prognosis. The presented results prompt the conclusion that
      hypermethylation of p16 is the major mechanism for p16 gene inactivation in early
      stage NSCLC and could be a useful molecular marker for the prognosis.

PMID- 11820618
TI  - P16INK4a point mutations and promoter hypermetylation in bronchial preneoplastic
      lesions.
AB  - The aim of this study was to determine p16INK4a point mutations and promoter
      hypermethylation in tumour cells and bronchial preneoplastic lesions in 32
      surgically resected lungs due to primary squamous cell carcinoma. P16 point
      mutations were detected in 1 (3%) and promoter hypermethylation in 12 (31%) of 32
      squamous cell carcinomas. The status of p16 was further characterized in 38
      premalignant lesions including squamous metaplasias without dysplasia, squamous
      metaplasias with mild, moderate and severe dysplasias and 4 carcinomas in situ.
      No p16 point mutations have been found in premalignant or CIS lesions.
      Methylation of p16 was detected in 1 of 8 (12.5%) cases of squamous metaplasias
      without dysplasia, in 1 of 10 (10%) cases of squamous metaplasias with mild
      dysplasia, in 1 of 9 (11%) cases of squamous metaplasia with moderate dysplasia
      and in 2 of 7 (28.5%) cases of severe dysplasias, as well as in 1 of 4 (25%)
      carcinomas in situ. This investigation indicates that P16INK4a supressor gene
      point mutations are rather late event and inactivation of this gene by promoter
      hypermethylation is early and likely critical in bronchial cancerogenesis.

PMID- 11820619
TI  - Significance of cell adhesion molecules, CD56/NCAM in particular, in human tumor
      growth and spreading.
AB  - Cell adhesion molecules (CAM) represent a large group of cell surface protein
      moieties with distinctive biological functions. In physiological terms they
      ascertain cell to cell contact such as cell cohesion of epithelia, condition cell
      migration and transmigration via biological membranes such as blood vessel walls,
      provide means for homing cells in a new microenvironment etc. These features of
      CAM are exploited by tumor cells to grow and spread in a tumor bearing host.
      CD56/N-CAM antigen is 140 kD isoform of neural cell adhesion molecule. N-CAM
      belongs to the large Ig superfamily of CAMs. CD56 can be traced at various sites,
      including nervous tissue, neuro-muscular junctions, neuroendocrine and endocrine
      organs. It is well known as a differentiation antigen of natural killer (NK)
      cells. Its role and function are far from clear, but its adhesion properties are
      evident in cell-cell (homophilic) interactions. CD56 has been, however,
      demonstrated the cells various human malignancies. Tumors of the nervous system
      such as neuroblastoma, are well known to express this marker. Malignant lymphomas
      of T-NK cell origin bear CD56, as well as multiple myeloma, melanoma and some
      cancers of epithelial origin. These data suggest that CD56/N-CAM antigen is, in
      some unknown manner involved in tumor biology.

PMID- 11820620
TI  - Observations as to male fertility in the Flemish environment and health studies.
AB  - We report the observations made on 101 healthy non-smoking men aged 21-40 (50
      from two industrial suburbs of the big city of Antwerp and 51 from Peer, a
      predominantly rural municipality with 14,622 inhabitants, 70 km east of Antwerp,
      chosen as the "control" area in spite of its intensive agriculture). Persons with
      known occupational exposures, persons working in a region with characteristics
      clearly different from the area of residence, and people commuting over long
      distances were excluded from the study. Sperm morphology was significantly worse
      in Peer than in Antwerp. Serum testosterone levels were significantly lower in
      Peer than in Antwerp. The proportions of men with very low and low serum
      testosterone levels, of men with very low and low spermatozoa concentrations and
      of men with very low and low percentages of spermatozoa with normal morphology,
      were all higher in Peer than in Antwerp. We speculate that both the lower
      testosterone concentrations and the poorer sperm quality are due to disturbance
      of the hypothalamic-pituitary-testicular function by hormone disrupters. Our data
      suggest that exposure to levels of environmental pollution which are widespread
      in developed nations, can have unfavourable effects on endocrine equilibrium and
      may disturb male fertiline disrupters.

PMID- 11820621
TI  - Female infertility--effect of perinatal xenoestrogen exposure on reproductive
      functions in animals and humans.
AB  - Environmental chemicals with inherent estrogenic activity are supposed to be
      responsible for the decrease of quantity and quality of human sperms during the
      past 40 years. The current hypothesis is that estrogenic agents acting during
      fetal life may lead to impaired development of the testes and of the male
      reproductive tract in the human as well as in several wildlife species. However,
      from clinical and experimental data it is known, that estrogens may also lead to
      impairment of female reproductive functions. Perinatal application of DDT,
      octylphenol and benzylbutylphthalate resulted in persistent estrus in rats, in-
      and subfertility, respectively, and impaired sexual behaviour. Epidemiological
      and experimental data speak in favour of environmental estrogens to be one cause
      for the development of polycystic ovaries, being the most important reason for
      female infertility in the human.

PMID- 11820622
TI  - Estrogen receptor based in vitro assays for the evaluation of endocrine
      disrupters.
AB  - An increasing number of environmental chemicals is suspected to act similarly as
      endogenous estrogens at concentrations far below the so called "No Observed
      Adverse Effect Levels". In man, as in wildlife, these substances are held
      responsible for several reproductive disorders e.g. the decline in sperm quality
      and the increase in testicular cancer incidence in different countries worldwide.
      Several in vitro bioassays have recently been developed to screen single
      compounds for their ability to bind to estrogen receptors (ER) resulting in a
      hormone specific response. However, divergent results from these assays indicate
      the lack of validation and standardisation. Moreover, the proven cell specificity
      of estrogen response questions the relevance of the observed effects and
      necessitates the development of assays in a fertility related cellular context.

PMID- 11820623
TI  - Neurotoxic states and their investigation--possibility for early detection of
      poisoning.
AB  - A highly important function of the nervous system (NS) is to process the
      information arriving to us from external, environmental sources. This capacity
      may be discontinued by chemicals restricting the plasticity of the NS, disturbing
      its adaptability to the ever changing environment. NS and endocrine system are
      profoundly bound together, changes, disruption of the different regulatory
      endocrine levels by toxicants may take part in the development of manyfold neural
      disfunction. The various endocrine levels (integrative, modulatory, regulatory,
      effector, target gland, etc.) affecting neurotoxicity and affected by
      neurotoxicity are discussed. The NS is protected against some toxic insults but
      is rather sensitive to other ones. By electrophysiological and
      psychophysiological methods, used as sensitive biomarkers the signs of functional
      disturbances of the NS can be proved both in human investigations and in animal
      experiments at an early stage of low concentration intoxications when clinical or
      general laboratory symptoms do not indicate yet the moderate poisoning.

PMID- 11820624
TI  - The relevance of xenobiotic metabolism in the interindividual susceptibility to
      chemicals.
AB  - Biotransformation enzymes may catalyze either detoxication or bioactivation
      reactions; indeed, many xenobiotics exert their toxic effects after metabolic
      activation to electrophilic chemicals, interacting with nucleophilic sites on
      cellular macromolecules. On the other hand, by increasing xenobiotic
      hydrophilicity, the drug-metabolizing enzymes favors excretion of lipophilic
      chemicals, not allowing their bioaccumulation up to toxic levels. The expression
      of the enzymes of the drug-metabolizing system is modulated by genetic,
      pathological, developmental, environmental and dietary factors. Genetic
      polymorphism resulting in interindividual and interethnic variation in xenobiotic
      metabolism is responsible for differences in the susceptibility to chemical
      induced toxicity and carcinogenicity, allowing the identification of people at
      increased risk. Moreover, differences in drug metabolism may correspond to
      variability in drug response during pharmacological therapy, which can be
      manifest either as adverse reactions or as a lack of benefit.

PMID- 11820625
TI  - The role of physiologically based toxicokinetic models in biologically based risk
      assessment.
AB  - Biologically-based cancer risk assessment relies on mathematical models that
      represent the toxicokinetics and toxicodynamics of the xenobiotic in the body.
      Physiologically-based toxicokinetic (PBTK) models are used as a tool for
      predicting the target tissue dose of a xenobiotic from different routes of
      exposure, extrapolating from high doses to low doses and extrapolating between
      species. This paper reviews the role of PBTK models and their limitations in
      biologically-based risk assessment.

PMID- 11820626
TI  - Use of higher plants in the biomonitoring of environmental genotoxic pollution.
AB  - Genotoxicity is recognised as being the first step in carcinogenesis. Hence the
      identification ambient genotoxicity represents an important step in cancer risk
      assessment even if non-genotoxic mechanisms also occur. Genotoxicity can be
      assessed after exposure of populations to chemical or physical agents, as
      cytogenetic alterations, mutations or production of DNA/protein adducts. Well
      defined higher plants represent an excellent basis for cytogenetic evaluations
      after exposure to genotoxic pollutants, especially that the maturation of their
      gametes (meiosis) follows the same patterns as in animals and humans. We present
      a description of the Tradescantia Micronucleus Assay (TRAD-MCN) and results of a
      series of field evaluations after environmental pollution (urban settings,
      industrial sites, landfills). A significant correlation is observed between the
      intensity of the pollution and the ratio of micronuclei appearing at the tetrad
      stage of meiosis. The method is easy, requiring no special equipment,
      reproducible, rather inexpensive. It allows the establishment of "genotoxicity
      maps" and the follow-up monitoring of the polluted sites. In environmental
      monitoring, we consider the TRAD-MCN assay as the first-line procedure presenting
      the additional advantage of not involving human populations primary evaluations,
      thus avoiding psychological stress.

PMID- 11820627
TI  - Tradescantia-micronucleus bioassay for detection of carcinogens.
AB  - The Tradescantia-Micronucleus (Trad-MCN) bioassay is one of the tests used in the
      International Program on Plant bioassays (IPPB) under the auspices of the United
      Nations Environment Programme (UNEP). Using chromosome damage as the indicator of
      the carcinogenic properties of environmental agents, the Trad-MCN bioassay is a
      quick and efficient tool for screening carcinogens in gaseous, liquid and solid
      forms. Test results can be obtained within 24-48 hr after the exposure either on
      site or in the laboratory. The international standard protocol of this test was
      published in 1994 and a list of test results of carcinogens and clastogens
      compiled from publications in the last 23 years will be presented. Under the
      IPPB/UNEP, more than 40 institutes including public health, medical and cancer
      research in the major countries of the world are carrying on the monitoring task
      on genotoxicity of polluted air, water and soil. At the same time, the Trad-MCN
      can be used in a global scale to detect carcinogens as a preventive measure of
      cancer.

PMID- 11820628
TI  - Mutagenesis, apoptosis, basic relation to carcinogenic models.
AB  - Cancer arises from an accumulation of mutations as well as changes in the
      expression pattern of genes mainly involved in cell cycle regulation, DNA repair
      and apoptosis, which promote clonal selection of cells with an increasingly
      malignant phenotype. Although a single mutant gene may not be able to redirect
      the growth program of a normal cell, the multiplicity of downstream targets of a
      deregulated molecule and the extensive cross-talk between biochemical pathways
      suggest that cellular context and genotype are of great importance in cancer
      initiation, while gene activation and inactivation events may not be independent.
      Complex exposure patterns affecting molecular targets exhibiting multiple
      intracellular interactions add a significant percentage of uncertainty when
      assessing cancer risk.

PMID- 11820629
TI  - Pulmonary neuroendocrine cells in physiology and pathology.
AB  - Pulmonary neuroendocrine cells are scant and widespread within the pulmonary
      epithelium. The function they play is not fully known, more studies are needed to
      clearly define it. They have been implicated however, as either the culprit or
      victim of many pulmonary diseases. That is the reason, why so many scientists
      take interest in the pulmonary neuroendocrine system. This paper reviews current
      information regarding pulmonary neuroendocrine cells, their origin, morphology,
      ontogeny, role, neuroendocrine cell markers, dysplasia and hyperplasia of
      pulmonary neuroendocrine cells in various conditions, diffuse idiopathic
      pulmonary neuroendocrine cell hyperplasia, typical carcinoid, atypical carcinoid,
      small-cell lung carcinoma, large-cell neuroendocrine carcinoma and the unusual
      spectrum of pulmonary neuroendocrine tumours.

PMID- 11820630
TI  - Immunoreactivity of neuroendocrine cells in the respiratory tract in rats with
      experimental uremia after thyroparathyroidectomy.
AB  - Animals with experimental uremia, which underwent thyroparathyroidectomy, reveal
      numerous metabolic disorders that can influence morphology and activity of
      endocrine cells of the scattered neuroendocrine system. The aim of the study was
      the evaluation of the influence of thyroparathyroidectomy in rats with chronic
      renal failure on APUD system cells localized in the respiratory tract. The
      examination was conducted on the group of 20 rats. Thyroparathyroidectomy was
      performed 30 days after nephrectomy. Fragments of the lungs and trachea were
      collected 14 days after the operation. Routinely prepared paraffin sections were
      stained with H+E and with silver method. The immunohistochemical reactions were
      conducted with the use of antibodies against calcitonin (CT), synaptophysin
      (SPh), somatostatine (ST), and neuron-specific enolase (NSE) The results were
      estimated in light microscope on the basis of stain reaction of endocrine cells.
      Our examination showed that chronic renal failure affects the functioning of
      endocrine cells. We also observed the increase in APUD system cell number in the
      trachea and the lungs after thyroparathyroidectomy in uremic rats.

PMID- 11820631
TI  - Gastric endocrine cells in rats with uremia and after thyroparathyroidectomy.
AB  - The decrease in active kidney parenchyma amount causes disorders in hormone
      secretion processes and their inactivation failure. Experimental
      thyroparathyroidectomy is connected with an abrupt reduction in endocrine cells
      and hormones produced by them, which can be a stimulating factor as far as the
      increase and intensity of endocrine gastric cells activity is concerned. The aim
      of the study was the histomorphological and immunohistochemical evaluation of
      these cells in the gastric pylorus. Thyroparathyroidectomy was performed in rats
      30 days after nephrectomy. Fragments of gastric pylorus were collected 14 days
      after the operation. Paraffin sections were stained with H+E and silver method.
      Immunohistochemical reactions were conducted using antibodies against calcitonin
      gene-related peptide (CGRP), somatostatin (ST), synaptophysin (SPh), neuron
      specific enolase (NSE), and chromogranin (CgA). The results showed an increase in
      number of endocrine cells in stomachs of rats in experimental group as compared
      to controls. Endocrine cells were larger and contained more secretory granules.

PMID- 11820632
TI  - K-ras codon 12 mutations detected with enriched PCR method in operable non-small
      cell lung cancer.
AB  - Activated point mutations of the K-ras gene are one of the most common genetic
      alterations found in human malignancies, including lung cancer, and are largely
      limited to adenocarcinomas. Using a highly sensitive assay for codon 12 K-ras
      mutation detection, called enriched PCR, we investigated 130 radically resected
      stage I-IIIa non-small cell lung cancer (NSCLC). There were statistically less
      positive results for squamous cell carcinoma (1.3%) than for adenocarcinoma
      (42.4%) and large cell carcinoma (27.8%). No statistically significant
      association between results of K-ras mutations and TNM stage of disease was
      found. In stage I of adenocarcinoma patients the incidence of K-ras mutations was
      similar to that in stage II or IIIa (40%, 42.9% and 42.9%, respectively). The
      results of our study showed that K-ras mutations might play an important role in
      pathogenesis of pulmonary adenocarcinoma due to its high prevalence in the
      operable tumours.

PMID- 11820633
TI  - K-ras codon 12 mutations may be detected in serum of patients suffering from
      adeno- and large cell lung carcinoma. A preliminary report.
AB  - We investigated the presence of K-ras mutations in the serum of 40 patients with
      respectable stages of adeno- and large cell lung carcinomas. Mutations in codon
      12 of the K-ras gene were examined by enriched PCR method in DNA extracts from
      surgical specimens and serum samples. K-ras mutations were detected in 20 (51%)
      of 39 analyzed tumours, and in 7 (35%) of 20 patients with K-ras gene mutation
      positive tumours, a mutation was found in the serum DNA. We also found K-ras
      mutation in two (10.5%) of 19 serum samples obtained from patients whose tumours
      were not found to harbor mutation and in one serum sample from patient without
      tumour sample available for investigation. All of the 14 control healthy persons
      were negative for serum DNA K-ras mutation assay. Although our results are
      preliminary they show that K-ras mutation may be detected in serum of patients
      suffering from adeno- and large cell lung carcinomas and confirm the suggestion
      that at least a part of a free-cell extracellular blood DNA in cancer patients
      has neoplastic origin and may become a noninvasive target for genetic
      investigations of lung cancer patients.

PMID- 11820634
TI  - The coexistence of tuberculosis infection and lung cancer in patients treated in
      pulmonary department of Medical Academy in Lublin during last ten years (1990
      2000).
AB  - The coexistance of tuberculous infection (TB-infection) and lung cancer in
      patients treated in Pulmonary Department of Medical Academy in Lublin during last
      ten years (1990-2000) has been evaluated. Inclusion criteria involved: aging from
      50 to 80 years, tobacco smoking, tuberculous infection in present or in past,
      lung cancer. All analyzed patients (32 males, 13 females) were heavy smokers
      (from 10 to 70 cigarettes per day, during at least 5 years). 27 patients were
      suffered from lung tuberculosis in past, the rest of them had active tuberculous
      infection. In 19 cases we detected carcinoma planoepitheliale, in 13 cases
      carcinoma macrocellulare, in 7 cases carcinoma microcellulare and in 6 cases
      adenocarcinoma. We concluded, that increased occurrence of lung cancer in TB
      reinfected patients may be connected with immunodepression caused by chronic TB
      infection. In patients with new active TB-infection in whom the clinical status
      and chest X-ray were getting worse in spite of antituberculotic treatment
      recommended procedures for cancer diagnosis were performed. We suggest that bad
      results of anti-tuberculotic treatment in TB-infected patients are not always
      caused by bactericidal resistance. In these cases, the proper diagnosis of lung
      cancer should be considered.

PMID- 11820635
TI  - Fractal geometric analysis of lung cancer angiogenic patterns.
AB  - For medical images, the fractal dimension D may be used as an index of
      irregularity. The angiogenesis patterns of lung cancer were analysed by means of
      the perimeter-area and box counting algorithms. The fractal nature of all images
      in the sense of the perimeter-area method and of 68% images in the sense of the
      box-counting method suggest the possibility to use the fractal dimension as a new
      non-morphometric parameter evaluating angiogenic processes in neoplasms.

PMID- 11820636
TI  - Association of polymorphism of LTalpha and TNF genes with Graves' disease.
AB  - Graves' disease (GD) is an autoimmune disease, which develops on the basis of an
      interaction between genetic, environmental and endogenous factors. GD is
      associated with some HLA genes. Closely linked with them are TNF genes (TNF and
      LTalpha). Their role in the pathogenesis of GD is still unclear. Two functional
      polymorphisms within TNF genes include a substitution of G with A in intron I of
      LTalpha gene and the same one at position -308 in the TNF gene promoter. We
      carried out a case-control study for the analysis of the contribution of TNF
      genes to GD in Polish patients. 156 patients with GD diagnosed by clinical data
      were investigated and compared to 80 healthy persons with negative familial
      anamnesis. Both TNF and LTalpha were analysed by PCR/Nco I RFLP. The allelic
      frequency of the rarer TNF2 (A) allele, was 24.7% in GD patients, significantly
      higher than in healthy persons (9.3%; p<0.0001). The OR was 4.38 for this allele.
      The frequency of heterozygotes was 41.8% in GD, as compared to 13.6% in the
      control group. The allelic frequency of the rarer LTB*1 (G) allele was also
      significantly increased: from 21.9% in the control group to 37.2% in GD patients
      (p<0.01; OR 2.81). The frequency of heterozygotes was 48.7% in GD, and 28.8% in
      the control group. The results indicate that TNF genes may contribute to GD in
      the Polish population.

PMID- 11820637
TI  - Low activity of the ahr gene in the ahr dd C57BL congenic mice does not prevent
      the depression of birth rates observed as result of cigarette smoke exposure.
AB  - The ahr gene product is a ligand-activated transcription factor which regulates
      the expression of a number of enzymes involved in the metabolism of aryl
      hydrocarbons and mediates the effects of dioxins on tumour promotion. We have
      assessed the cigarette smoke induced depression of the reproductive capacities in
      the ahr dd C57BL congenic mice and its crosses with C57BL ahr bb mice. The in
      vivo exposure of animals to toxic concentrations of cigarette smoke during the
      period of pairing and the early pregnancy was shown by us to affect the
      reproduction. The transmission of the ahr b and ahr d alleles was assessed by
      genotyping the STR polymorphism at D12Mit2 locus linked with the ahr gene.
      Following the exposure to cigarette smoke the changes in the reproductive
      capacity of the studied mice have been assessed in relation to the presence of
      the ahr d allele by measurements of the changes in the rates of conceptions,
      abortions, births and the number of newborns per female after pairings differing
      in ahr gene alleles and in the expected ahr d allele frequencies in the progeny.
      The results indicates that the low activity ahr d allele may decrease the
      abortive effects of cigarette smoke exposure, but does not confer resistance to
      the depression of births rates following this exposure.

PMID- 11820638
TI  - Effect of tyrphostins on programmed cell death in colon adenocarcinoma cell line
      LS-180.
AB  - Programmed cell death is an important process in the regulation of cellular
      proliferation, rest, differentiation and death. It is a genetically controlled
      process with characteristic biochemical and morphological features. Apoptosis
      directly regulates tumorigenesis and its induction could be a useful method of
      cancer therapy. Cancer cells could be influenced by some factors which induce
      apoptosis. We investigated the influence of tyrphostins, that specifically
      inhibits protein tyrosine kinases and stops the cell cycle in apoptosis of the
      colon adenocarcinoma cell line LS180. We used them at the concentration of 1-10
      microM for 24 and 48 hours. We detected apoptosis using techniques that monitor
      either biochemical and morphological features of this process, such as staining
      with 7-amino-actinomycin D, staining with Grunwald-Giemsa, TUNEL reaction, in
      situ hybridization and with immunoperoxidase staining procedures. We examined the
      expression of genes and proteins connected with programmed cell death (p53, c
      myc, p21, bcl-2). We estimated the results by cytophotometry and documented them
      by colour photography. We found that tyrphostin rapidly inhibits the cell cycle,
      particularly at the concentration of 5 microM. The expression of genes and
      proteins was strongly correlated with the increased apoptotic cell death
      conforming to the results of TUNEL and staining methods.

PMID- 11820639
TI  - The clinical value of the determinations in the serum of zinc concentration in
      women with breast cancer.
AB  - The clinical usefulness of the determinations of the zinc serum concentration at
      different stages of the breast cancer diagnostic process was evaluated in the
      present work. On the basis of the analysis of 182 women surgically treated
      because of this neoplasm, a statistically significant dependence was shown
      between the frequency of occurrence of hypozincemia and the progression of the
      cancer, its histological form, and the microscopic state of the axillary lymph
      nodes. The clinical usefulness was also shown by the determinations of the
      zincemia in the post-operative monitoring of patients with breast cancer. The
      critical value was also determined for the microelement concentration below which
      a statistically significantly high risk of occurrence of distant metastases
      appears.

PMID- 11820640
TI  - The influence of glyco-nitric oxide conjugate on proliferation of breast cancer
      cells in vitro.
AB  - The aim of the study was to evaluate the influence of a nitric oxide donor: Glyco
      2-SNAP on the proliferation status of two breast cancer cell lines: MDA-MB-231
      and MCF-7. The study was performed by the thymidine incorporation method as well
      as by the immunocytochemical detection of the Ki-67 antigen. We found that the
      donor significantly inhibits the process of proliferation. The effect of the
      Glyco-2-SNAP is significant in both lines, however stronger in MDA -MB-231 cells
      where the donor at 100 microM inhibited DNA synthesis from 70462.000 dpi (SD +/
      2066.175, n=4) for control to about 3120.250 dpi (SD +/-971.689 n=4). In UCF-7
      cells the control gave 31142.500 dpi (SD +/-712.9214, n=4) and the treatment with
      100 microM of Glyco-2 SNAP resulted in 4095.50 dpi. (SD +/-315.723, n=4). In both
      lines SNAP, classical NO donor also had an inhibitory effect but much higher
      concentrations. Ki-67 protein expression was significantly influenced by Glyco-2
      SNAP at 100 microM (42.5% +/-6.45) concentrations in MDA-MB 231. No effect of G
      SNAP was seen in MCF-7 cells. The control staining for both lines was about 90%.
      Our results presesent the possibility of exploiting a novel kind of NO donor as a
      potential mode of treatment that may be an alternative to classical therapeutic
      strategies in breast cancer.

PMID- 11820641
TI  - Small cell carcinoma of the uterine cervix--an uncommon variant of cervical
      cancer with neuroendocrine features.
AB  - Small cell carcinoma (SCC) of the uterine cervix represents an uncommon variant
      of cervical cancer with an extremely aggressive biologic behavior, minimum
      survival chances and rapid and fatal clinical course. This retrospective study
      included 73 cases of patients treated for invasive squamous carcinoma of the
      uterine cervix at stages Ib and IIa at the Department of Gynecology in the years
      1996-2000. Six patients (8%) with SCC were identified among all cases, sharing
      the clinical features of young age and early failure of appropriate radical
      treatment in the presence of apparently low stage disease. Neuroendocrine
      cellular characteristics were assessed by the biotin-streptavidin-peroxidase
      (LSAB) method using antibodies against neuron-specific enolase (NSE; DAKO),
      chromogranin A (CGA; DAKO) and synaptophysin (SYN; DAKO). All tumors examined
      were positive for NSE and/or CGA and/or SYN. Although the presence of
      neuroendocrine features appears to correlate with decreased survival, the number
      of patients is not large enough to determine statistical significance. However,
      the results confirm that SCC of the uterine cervix is one of the most aggressive
      tumors of the female genital tract.

PMID- 11820642
TI  - The European strategy on endocrine disrupters: progress to date and EU/US
      cooperation.
AB  - The European Commission has been active in the field of endocrine disrupters
      since 1995. Its first actions were to fund research projects through the Fourth
      Framework Programme for Research and Development covering various aspects of the
      issue (identification of endocrine disrupters, environmental and human health
      impacts). This involvement in research has continued through the Fifth Framework
      Programme and increased to this day. The publication of a specific call for
      proposals on endocrine disrupters on May 31, 2001 bears witness to these efforts.
      In parallel, the policy profile of the issue quickly rose and led to the adoption
      of the Community Strategy on Endocrine Disrupters (COM (1999)706 final) in 1999.
      This strategy identifies actions short, medium and long term and is supported by
      the European Parliament and the European Council. Its short-term actions focus on
      the establishment of a list of substances for further evaluation of their role in
      endocrine disruption and on the use of existing legislation to control the risk;
      the medium-term actions focus on the identification and assessment of endocrine
      disrupters as well as on further research to better understand the ED phenomenon,
      and the long-term actions focus on legislative actions to protect human health
      and the environment. These European developments have gone hand in hand with
      international cooperation with the USA on research (in the frame of the EC/US S&T
      cooperation agreement), with the WHO on health issues and with the OECD on
      screening and testing issues.

PMID- 11820643
TI  - Characterization of a novel protein inhibitor of protein kinases specific to
      acidic ribosomal proteins.
AB  - The ribosomal stalk composed of acidic P1/P2 proteins and protein P0 is involved
      directly in the interaction of the elongation factors and mRNAs with the ribosome
      during protein synthesis. All P proteins are found to be phosphorylated in
      eucaryotic organisms. In Saccharomyces cerevisiae five different cAMP-independent
      protein kinases phosphorylating P proteins have been identified and
      characterized. In contrast to many other protein kinases, relatively little is
      known about inhibitors of these enzymes. A new protein inhibitor of protein
      kinases has been purified and characterized. It is a small (18.5 kDa) and acidic
      (pI = 4.2) protein with high inhibitory potency for PK60S and CK 2. The inhibitor
      is competitive with respect to protein substrates with Ki values in the range of
      approximately 6.5 microM for PK60S and approximately 22 microM for CK 2.

PMID- 11820644
TI  - The expression of oncogenes in tumour tissues of breast carcinoma patients.
AB  - The balance between Bcl-2 and c-Myc and c-Jun seems to be an important
      determinant of cellular sensitivity to the induction of apoptosis. High
      expression of Bcl-2 was noticed to be strongly related to low rates of apoptotic
      cell death. The mean value of the apoptotic index was 45.0% in Bcl-2-negative
      tumours and 7.5% in Bcl-2-positive tumours. C-Myc and c-Jun accumulation were
      associated with the absence of Bcl-2 expression and with increased apoptotic
      activity. The loss of Bd-2 expression was strongly correlated with increased
      apoptotic cell death. The inverse correlation is between apoptotic and mitotic
      index. A high mitotic index exists in most patients with a low apoptotic index.
      Bcl-2, c-Myc and c-Jun does not only take part in cell death, but also in cell
      division in breast carcinoma cells in which the regulation of cell division and
      cell death are strictly connected.

PMID- 11820645
TI  - Preliminary evaluation of mast cells in rats with an experimental fibrosarcoma
      induced by 3-methylcholanthrene.
AB  - The aim of the study was the evaluation of mast cells in experimental
      fibrosarcoma induced in the rats' skin. Experiments were carried out on 50 male
      Wistar rats divided into three groups: 1. The cancer was induced in 34 rats' by
      onefold subcutaneous injection of 0.2 mg 3-methylcholanthrene in 0. 25 ml of
      olive oil; 2.--8 rats received subcutaneous injection of 0.25 ml olive oil; and
      3.--8 rats, no treatment. The tumors developed after 14-35 weeks. The examined
      tumors had the mass of 1 g to 176 g--mean 15 g. Tissue material was fixed in
      Carnoy's or Bouin's fluid. Paraffin sections were stained with hematoxylin and
      eosin and using Azan methods. Mast cells were stained with alcjan blue+saphranin
      and with toluidine blue in pH 1.5. Immunohistochemical reactions detecting
      tryptase in mast cells and von Willebrand Factor in endothelial cells were also
      performed--using specific antibodies (DAKO) and ABC complex. We have found a very
      significant growth of the quantity of mast cells in the connective tissue of
      tumours. The distinct increase in immunostaining was found for tryptase in mast
      cells of the tumor periphery zone, where most areas of strong neoangiogenesis
      were found.

PMID- 11820646
TI  - Antioxidant status and proteolytic-antiproteolytic balance in colorectal cancer.
AB  - Free radicals participate in the development of cancer. When the antioxidant
      defence system is not longer capable to destroy free radicals they may cause
      lipid and protein oxidation. Lipid peroxidation products also modify proteins. In
      such a situation the proteolytic-antiproteolytic balance existing in the blood
      may be changed. Therefore the aim of this study was to examine the correlation
      between antioxidant status and activity of proteolytic enzymes and their
      inhibitors in cases of colorectal cancer. This study included 55 patients with
      colorectal cancer. The blood was taken before surgery and plasma was collected.
      Total antioxidant status, the levels of lipid peroxidation products
      (malondialdehyde and 4-hydroxynonenal) and activity of cathepsin G, elastase and
      their inhibitors (alpha-1-antitrypsin and alpha-2-macroglobulin) were determined
      in plasma. It was shown that during the development of cancer total antioxidant
      status was signficantly decreased while lipid peroxidation products were
      increased. Activity of alpha-2-macroglobulin was decreased and activity of
      determined enzymes was not significantly changed. The observed changes indicate a
      shift in proteolytic-antiproteolytic balance which may enhance carcinogenesis.

PMID- 11820647
TI  - Management of patellofemoral arthrosis in middle-aged patients.
AB  - Patellofemoral arthrosis is one of the most common causes of knee pain in middle
      aged patients, and is often associated with patellofemoral malalignment. A
      correct diagnosis is established by history taking and physical and radiographic
      examinations of the knee. The initial treatment of choice is conservative
      treatment, which includes anti-inflammatory drugs, use of a knee brace,
      quadriceps-strengthening exercises, physical therapy, and modification of
      activity. Surgery is indicated when patients fail to improve after at least 6
      months of conservative treatment and are functionally disabled. Lateral
      retinacular release and proximal realignment are performed only in selected
      cases. Distal realignment by anteromedial transfer of the tibial tubercle is the
      most effective method for treating patients with patellofemoral arthrosis. The
      magnitude of anteromedial transfer of the tibial tubercle must be individualized,
      and rigid internal fixation enables immediate postoperative rehabilitation. In
      knees with patellofemoral arthrosis with no malalignment, a 20-mm anterior
      displacement without medial transfer of the tibial tubercle is suggested. A 15-mm
      anterior displacement plus 5 to 10 mm of medial transfer of the tibial tubercle
      is recommended in knees with patellofemoral arthrosis and mild to moderate
      malalignment. In knees with severe malalignment, 15 mm of medial transfer and 10
      mm of anterior displacement are recommended. A triple osteotomy is considered in
      knees with patellofemoral osteoarthrosis and patella baja. Patellofemoral
      resurfacing arthroplasty is only done in carefully selected patients. A
      patellectomy should be avoided if at all possible. Total knee arthroplasty is
      indicated in knees with bi- or tricompartmental osteoarthritis.

PMID- 11820648
TI  - Effects of retinoic acid on pre-implantation embryo development in mice.
AB  - BACKGROUND: In a previous study we had investigated the effect of in utero
      retinoic acid (RA) exposure on early post-implantation development at the
      blastocyst stage before implantation and immediately after implantation to
      understand the possible roles of RA in embryogenesis. The results showed that
      excess RA affected early post-implantation embryogenesis adversely. We designed
      the present study to investigate the effect of in utero RA exposure on pre
      implantation embryos. METHODS: In the prospective animal study, pregnant female
      mice received early pre-implantation peanut oil with 50 mg/kg t-RA or 100 mg/kg t
      RA by oral gavage on the morning of day 1 and 2 or late pre-implantation exposure
      on the night of day 2 and morning of day 3 of gestation. Mice were sacrificed
      late in day 3. The number and morphology embryos were recorded. RESULTS: All mice
      given oral RA were sacrificed on the same day. The mean number of embryos per
      mouse and the percentage of different embryo stages in the t-RA treated mice
      administered at early pre-implantation embryo or late pre-implantation embryo
      stage were not significantly different from the controls. The mean number of
      embryos per 50 mg/kg mouse and the percentage of expanded blastocysts or early
      blastocysts/morulas did not differ from controls. In addition, the percentage of
      expanded blastocysts or early blastocysts/morulas was also not significantly
      different from the control group in 100 mg/kg late pre-implantation mice.
      CONCLUSION: Mouse embryo development may not experience dose related adverse
      effects from non-physiological RA exposure during pre-implantation.

PMID- 11820650
TI  - Implementation of whole body scanner for determining somatotype index at Chang
      Gung Memorial Hospital.
AB  - BACKGROUND: Body mass index (BMI) and waist-hip ratio (WHR) using 1-dimensional
      circumference data have been proven to be highly related to blood pressure and
      total cholesterol; these 2 indices have been widely used as health indicators in
      preventive diagnosis and health examination. Sophisticated software, which allows
      calculation of the triangular mesh related to the body surface in 3D space, is
      capable of computing the circumference, width, sectional surface, volume, and
      surface area of the body. METHODS: Chang Gung Whole Body Scanner (CGWBS) was used
      to capture 3D whole body surface images. In this study, the human body was
      divided into 10 segments consisting of the head, breast, wrist, hip, upper arm,
      forearm, hand, thigh, calf, and foot. Five independent assessments were made on a
      total of 32 anthropometric sites, including 12 circumferences, 3 widths, 3
      profile areas, 7 surface areas, and 7 volumes. In this study, the somatotype
      index (SI) was computed through anthropometric data after 1,323 subjects were
      investigated. Correlation analysis was used to describe the relationship between
      BMI, WHR, SI, and anthropometric data. One-way analysis of variance (ANOVA) and
      Duncan's multiple range tests were used to examine differences between
      examination variables across sex and SI groups. RESULTS: This study found 4
      somatotypes from anthropometric data. SI determined by CGWBS has better
      correlation with anthropometry than WHR or BMI. Of the 644 male subjects, 155
      were in the ectomorph group, 232 in the semi-mesomorph group, 136 in the full
      mesomorph group, and 121 in the endomorph group. Of the 679 female subjects, 160
      were in the ectomorph group, 235 in the semi-mesomorph group, 168 in the full
      mesomorph group, and 116 in the endomorph group. CONCLUSION: The results show
      that SI has great potential to perform precise somatotype classification.

PMID- 11820649
TI  - Klebsiella pneumoniae bacteremia: community-acquired vs. nosocomial infections.
AB  - BACKGROUND: This study attempted to determine the clinical manifestations and
      influential factors affecting the prognosis of patients with community-acquired
      and nosocomial bacteremia of Klebsiella pneumoniae (K. pneumoniae). METHODS: We
      retrospectively reviewed the medical records of 211 patients who had a clinically
      significant episode of K. pneumoniae bacteremia from January 1997 until December
      1999. RESULTS: Most reports describe K. pneumoniae bacteremia as typically
      nosocomial, but in our study approximately 3 of 4 episodes were community
      acquired. Without including "unknown origin", the most common infectious site for
      both community-acquired and nosocomial bacteremia was the hepatobiliary tract.
      The overall mortality for all 211 patients with K. pneumoniae bacteremia was
      25.1%. Significantly higher mortality rates occurred in patients who were elderly
      (> 65 years), had a nosocomial infection, for whom the respiratory tract was the
      portal of entry, and ultimately fatal conditions or acute complications were due
      to shock or renal insufficiency. CONCLUSIONS: Patients with community-acquired
      and nosocomial bacteremia had different types of underlying diseases. Isolates
      from nosocomial infections were significantly more frequently resistant to
      aminoglycosides, antipseudomonal penicillin, and all three generations of
      cephalosporins. In this regard, an aggressive empirical therapeutic approach to
      infections of K. pneumoniae is suggested.

PMID- 11820651
TI  - Proton magnetic resonance spectroscopy of cerebral glioma after irradiation.
AB  - BACKGROUND: Conventional magnetic resonance imaging (MRI) is commonly employed to
      assess cerebral gliomas after radiotherapy, but it cannot always differentiate
      tumor regrowth from post-irradiation changes. In this study, we utilized magnetic
      resonance spectroscopy (MRS) to evaluate changes in cerebral metabolites in
      patients with a cerebral glioma after irradiation. METHODS: Over a period of 3
      years, we performed MRS after MRI whenever soft tissue masses were found on
      magnetic resonance (MR) images. A total of 122 MR spectra of 58 patients was used
      for analysis. Spectral interpretations were based on integral values of the N
      acetylaspartate (NAA) and choline (Cho) compounds relative to
      phosphocreatine/creatine (Cr). RESULTS: Our MRS study showed that higher Cho/Cr
      ratios occurred in regrowing gliomas than for stable diseases (range, 0.9 to 9.5
      vs. 0.4 to 2.1; mean, 3.0 vs. 1.2). A greater increment in the Cho/Cr ratio
      between successive studies was also noted in regrowing gliomas than for stable
      disease (range, 41% to 87% vs. < 32%). No significant differences in NAA/Cr
      ratios or lactate were found between these 2 groups. None of our patients
      exhibited abnormal MR spectra in the mirror area of the contralateral brain.
      CONCLUSION: MRS provides valuable information about the metabolism of irradiated
      gliomas and can be used to exclude radiation encephalopathy of the contralateral
      brain. Cho is the most reliable indicator of a regrowing glioma. A high Cho/Cr
      ratio or substantial elevation in the Cho/Cr ratio between serial studies
      increases the likelihood of tumor regrowth. However, lower Cho/Cr ratios were
      inconclusive for determining if tumor regrowth or a stable process was occurring.

PMID- 11820653
TI  - Recurrence of pneumococcal meningitis due to primary spontaneous cerebrospinal
      fluid fistulas.
AB  - The authors report a case of pneumococcal meningitis which recurred 3 times in a
      Taiwanese boy due to spontaneous cerebrospinal fluid (CSF) fistulas. The first
      time occurred at the age of 2 years, and the second episode presented as
      meningoencephalomyelitis at the age of 6 years 10 months. Studies including serum
      levels of immunoglobulin and complements, brain magnetic resonance imaging, and
      coronal cranial computed tomography (CT) were negative for a specific etiology.
      The third episode of meningitis developed 2 months after the second episode.
      Repeated immunological studies and high-resolution CT of paranasal sinuses and
      temporal bones were negative. Technetium-99m diethylenetriamine pentaacetic acid
      (Tc-99m-DTPA) radionuclide cisternography revealed abnormal retention of
      radioactivity over the right mastoid area. Neurosurgery was undertaken to seal
      the dural tear and pack the petrosal fissure. Two years after surgery, he has had
      no further CSF leak age or meningitis. Tracing back the history, there was no
      head injury, cranial surgery, brain tumor, or hydrocephalus, which might have
      created CSF fistulas. Primary spontaneous CSF fistulas constitute the most
      reasonable diagnosis. In cases of recurrent bacterial meningitis, underlying
      anatomic defects should be carefully evaluated if there is no immune defect.

PMID- 11820652
TI  - Waveforms of the ductus venosus blood flow in normal human fetuses aged 8-38
      weeks.
AB  - BACKGROUND: We attempted to establish normal Doppler flow velocity waveform
      patterns in the human fetal ductus venosus (DV), and also to establish a
      standardized measurement technique. METHODS: Ductus venosus blood flow was
      measured in a prospective study involving 545 fetuses aged between 8 and 38 weeks
      in utero, the mothers of whom received prenatal care in Kaohsiung Chang Gung
      Memorial Hospital in a 12-month period in 1998-1999. Several DV hemodynamic
      parameters were assessed, including peak systolic velocity (DVP), peak
      systolic/diastolic (S/D) ratio, time-averaged velocity (TAMX), maximum velocity
      during atrial contraction (DVM), pulsatility index (PI), Pourcelot's resistance
      index (RI), and fetal heartbeat (FHB). RESULTS: Technically acceptable ductus
      venosus blood flow velocity waveform patterns were collected from 490 of 545
      pregnant women (89.9%). The mean +/- SD value for the peak systolic DV velocity
      during the time period of 8 to 38 weeks in utero was 0.33 +/- 0.11 meters/sec
      (m/s), the TAMX being 0.24 +/- 0.09 m/s. The maximum velocity during atrial
      contraction was 0.15 +/- 0.09 m/s, and the peak S/D velocity ratio was 2.5 +/-
      1.01. The PI, Pourcelot's RI and fetal heart beat were, 0.67(+/- 0.21), 0.64 (+/-
      0.11), and 163.3 (+/- 18.82 bpm), respectively. Significant increases in DVP,
      TAMX, and DVM with advancing gestational age were established, and decreases in
      PI, RI, S/D, and FHB with advancing gestational age were also observed.
      CONCLUSIONS: Further investigation of DV hemodynamics throughout pregnancy may
      enable a greater understanding of normal placental perfusion, the fetal venous
      return to the heart and associated cardiac function.

PMID- 11820654
TI  - Acute renal failure caused by rifampicin re-exposure with 10-year of interval.
AB  - A 53-year-old woman was treated for recurrent pulmonary tuberculosis with
      reintroduction of rifampicin after a medication-free interval of 10 years. After
      taking the first dose, she developed severe hemolytic anemia and oliguric acute
      renal failure and required temporary hemodialysis. The fulminant clinical course
      was compatible with rifampicin-induced acute renal failure. The renal function of
      this patient completely recovered after discontinuation of rifampicin and
      temporary hemodialysis. Since renal biopsy and anti-rifampicin antibodies cannot
      offer a definite diagnosis of rifampicin-induced acute renal failure, we must
      emphasize the importance of a clinical diagnosis of rifampicin-induced acute
      renal failure and complete history taking. Re-exposure is a critical factor. In
      this case, the rifampicin-free interval was as long as 10 years. Because of the
      feasible prognosis, reintroduction of rifampicin for recurrent pulmonary
      tuberculosis should not be abandoned, but the infrequent and life-threatening
      side effects should be kept in mind.

PMID- 11820656
TI  - Hemosuccus pancreaticus from a traumatic gastroduodenal pseudoaneurysm: an
      unusual cause of upper gastrointestinal bleeding.
AB  - Hemosuccus pancreaticus, blood entering the gastrointestinal tract through the
      pancreatic duct, is a rare and elusive form of gastrointestinal bleeding with
      diagnostic difficulties. We report a 37-year-old man who had recurrent
      gastrointestinal bleeding from erosion of a pseudoaneurysm of the gastroduodenal
      artery into the pancreatic duct. The lack of history of pancreatitis, associated
      symptoms, equivocal endoscopic findings, and the rarity of this entity resulted
      in a delay in diagnosis. Pancreatic duct stenosis detected during surgery
      suggested the lesion might have been caused by blunt abdominal trauma. A nearly
      total pancreatectomy and splenectomy were performed. The patient remained symptom
      free 8 months after the operation. This obscure cause of gastrointestinal
      bleeding should be considered when common causes of bleeding have been ruled out,
      even in the absence of pancreatitis.

PMID- 11820655
TI  - Endoscopic variceal ligation for intractable esophageal variceal bleeding in
      children with idiopathic extrahepatic portal vein occlusion: report of three
      cases.
AB  - Extrahepatic portal vein occlusion (EPVO) is an important cause of extrahepatic
      portal hypertension and variceal hemorrhage in children. We report 3 children
      with a diagnosis of EPVO and intractable esophageal variceal bleeding who
      underwent scheduled endoscopic variceal ligation (EVL) and prophylactic
      propranolol therapy for eradication of esophageal varices. Complete variceal
      obliteration was achieved in all 3 children following 3-4 treatment sessions.
      There were no significant complications or gastrointestinal hemorrhage during a
      follow-up period of 9 to 31 months after variceal eradication. In conclusion, EVL
      and long-term propranolol prophylaxis is safe and effective in eradicating
      bleeding esophageal varices in children with EPVO.

PMID- 11820657
TI  - Unruptured aneurysm of sinus of Valsalva with right ventricular outflow tract
      obstruction.
AB  - Aneurysm of the sinus of Valsalva (ASV) is a rare anomaly. It may be congenital
      or acquired basis. In pediatric patients, most are congenital in origin. It is
      frequently associated with other congenital disease, most frequently ventricular
      septal defect (VSD). Pathologically, this is due to the total absence of normal
      elastic fibers. Patients with ASV are generally asymptomatic unless aneurysm
      rupture occurs. Unruptured ASV with right ventricular outflow tract (RVOT)
      obstruction is very rare. Herein we describe an unusual ASV with RVOT obstruction
      associated with VSD in a 14-year-old boy. He had experienced heart failure and
      exertional dyspnea for 2 months. The diagnosis was made by echocardiography,
      angiography and surgery. After surgical repair of the VSD and resection of the
      ASV, dyspnea and heart failure were relieved. The patient remained well during
      the 3 years of follow-up.

PMID- 11820658
TI  - Combined cataract surgery and vitrectomy for breakthrough vitreous hemorrhage
      from age-related macular degeneration.
AB  - PURPOSE: To report combined cataract extraction (CE), posterior chamber
      intraocular lens (PCIOL) implantation, and pars plana vitrectomy (PPV) for
      concurrent cataract and breakthrough vitreous hemorrhage from age-related macular
      degeneration (AMD). METHODS: Retrospective case series. RESULTS: Six eyes were
      included in the study. The postoperative follow-up interval ranged from 3 to 22
      months (mean 8 months). Preoperative visual acuity (VA) ranged from 20/400 to
      hand motion. Postoperatively, 5/6 eyes had 2 or more lines of visual improvement.
      Three eyes were better than 20/200. CONCLUSIONS: Combined CE, PCIOL insertion,
      and PPV in selected patients with cataract and breakthrough vitreous hemorrhage
      from AMD was successful in improving VA in the majority of patients.

PMID- 11820659
TI  - Aqueous shunts for intractable glaucoma in infants.
AB  - BACKGROUND AND OBJECTIVE: To evaluate the long-term outcome of aqueous shunts in
      the treatment of infantile glaucoma refractory to conventional treatment.
      PATIENTS AND METHODS: The records of all patients up to 3 years of age managed
      with aqueous shunts for uncontrolled glaucoma between November 1990 and November
      1996 were retrospectively reviewed. Ten eyes of 6 patients were included in the
      study. RESULTS: The mean preoperative intraocular pressure (IOP) was 29.75 +/-
      4.15 (mm Hg; SD), with none of the eyes on antiglaucoma medication.
      Postoperatively, the mean IOP was 18.25 +/- 5.34 (mm Hg; SD) at a mean follow up
      of 50 +/- 25.6 (SD) months with 7 eyes on topical antiglaucoma medication. At the
      final follow up, 6 eyes were considered successfully controlled without
      reintervention, 2 more were controlled after shunt revision, and 2 were
      considered failures. CONCLUSIONS: Aqueous shunts were relatively effective in
      this series of infants with recalcitrant glaucoma.

PMID- 11820660
TI  - A comparative study of small incision trabeculectomy avoiding tenon's capsule
      with conventional trabeculectomy.
AB  - BACKGROUND AND OBJECTIVE: The purpose of this study was to compare the results of
      small incision trabeculectomy (SIT) avoiding Tenon's capsule vis-a-vis
      conventional trabeculectomy, and find a safe, effective alternative to
      conventional trabeculectomy with or without pharmacological wound modulation.
      PATIENTS AND METHODS: A controlled prospective study was conducted on 80
      consecutive open-angle glaucoma patients requiring glaucoma filtration surgery.
      They were divided into two groups: Group I (n = 40): patients undergoing
      conventional trabeculectomy; and Group II (n = 40): patients undergoing limbal
      approach SIT. Patients were followed up serially for a minimum of 12 months and
      their intraocular pressure was monitored. Success of the procedure was defined as
      an intraocular pressure (IOP) <22 mm Hg with no additional antiglaucoma
      medication or surgery, and achieving at least a 30% reduction from the initial
      IOP at which optic disc cupping and/or visual field changes occurred. RESULTS: A
      significant fall (P <0.0001) in the final mean IOP was present in both groups at
      all time intervals in comparison to their preoperative values. The final mean
      intraocular pressure achieved with conventional trabeculectomy was 18.90 +/- 4.86
      mm Hg versus 16.60 +/- 5.93 mm Hg with SIT. The final success rate of 90% was
      obtained with SIT vs 80% with conventional trabeculectomy. No major complications
      were encountered with either procedure although complications such as shallow
      anterior chamber and progression of cataractogenesis were seen more often in
      patients undergoing conventional trabeculectomy. CONCLUSION: Small incision
      trabeculectomy avoiding Tenon's capsule is a low-cost and safe alternative to
      conventional trabeculectomy that effectively reduces IOP in 90% of cases. The use
      of a small 2.5 mm limbal incision, which obviates the dissection of Tenon's
      capsule and absence of any major complication, suggests that this procedure be
      used more often in glaucomatous eyes needing filtering surgery.

PMID- 11820661
TI  - Implantation of second glaucoma drainage devices after failure of primary
      devices.
AB  - BACKGROUND AND OBJECTIVE: To evaluate the efficacy and safety of implantation of
      a second glaucoma drainage device for eyes that have failed a primary device.
      PATIENTS AND METHODS: Medical records of patients receiving a primary glaucoma
      drainage device at Bascom Palmer Eye Institute from January 1987 to October 1998
      were reviewed, of which 18 eyes of 18 patients were studied. Patients failing a
      primary glaucoma drainage procedure and receiving a second glaucoma drainage
      device were included in this study. The second eye in the same patient was
      excluded if a second drainage implant was required. All patients received a
      second device in a standardized fashion with the drainage tube inserted in the
      anterior chamber. Main outcome measures included: visual acuity, intraocular
      pressure (IOP), antiglaucomatous medication, length of follow up, and surface
      area of glaucoma drainage device. Success was defined as an IOP less than or
      equal to 21 mm Hg with or without medications, and at least a 20% reduction in
      IOP, without the need for additional glaucoma procedures. RESULTS: The mean
      postoperative IOP (19.6 +/- 9.4 mm Hg; range, 8-50 mm Hg) was significantly (P =
      0.006) lower than the mean preoperative IOP (29.5 +/- 8.1 mm Hg; range, 20-52 mm
      Hg) at last follow up (mean 19.6 +/- 13.6 months; range, 6-47 months). The mean
      number of postoperative antiglaucomatous medications (2.2 +/- 1.2; range 0-4) was
      statistically similar (P = 0.2) to mean preoperative number of antiglaucomatous
      medications (2.6 +/- 1.2, range 1-4). Using Kaplan-Meier estimates, successful
      IOP reduction was observed in 89%, 83%, 63%, and 37% of eyes at 6 months, 1, 2,
      and 3 years, respectively. Four patients (21%) had a decline in visual acuity.
      CONCLUSIONS: Implantation of secondary glaucoma drainage devices may be useful in
      eyes that have failed primary devices.

PMID- 11820662
TI  - Clinical applications of capsular tension rings in cataract surgery.
AB  - BACKGROUND: Although the open capsular tension ring was designed to manage
      zonular dialysis during cataract surgery, it also lowers the incidence of capsule
      contraction, stabilizes the capsular bag, and enhances IOL centration. With
      appendages, it provides a partial solution for those eyes with colobomata and
      aniridia. MATERIALS AND TECHNIQUES: Subsequent modifications to the capsular
      tension ring include the Cionni ring, capsular edge ring, coloboma ring, and
      aniridia ring. A square-edge design may inhibit posterior capsule opacification,
      and the aniridia and coloboma rings with appendages create an artificial it is in
      traumatic or congenital colobomata. RESULTS: Designs, functions, indications, and
      results of different types of capsular tension rings are reviewed, as well as
      applications in pediatric cases, and considerations for their routine use in
      adult cataract surgery. CONCLUSIONS: The potential benefits of capsular edge ring
      implantation in pediatric cataract surgery cases are explored.

PMID- 11820663
TI  - Clinically significant corneal astigmatism and pars plana vitrectomy.
AB  - PURPOSE: To report a rare and previously unappreciated potential wound-related
      complication of repeat pars plana vitrectomy (PPV) combined with anterior segment
      surgery. METHODS: From a total of 135 patients who had undergone PPV over a
      period of 15 months, 7 patients were identified on the basis of a visually
      disabling degree of astigmatism persisting at 3 to 4 months following their
      surgery. These patients were retrospectively studied from the standpoint of the
      numbers and combination of procedures they had experienced. Videokeratoscopy was
      employed as an objective method of documenting the astigmatism. RESULTS: The
      average astigmatism at the corneal plane in these 7 eyes was 4.5 diopters (D). In
      the 5 patients who required suture lysis for visual rehabilitation, the average
      corneal astigmatism was slightly greater than 5.0 D. In all cases, the
      astigmatism was a symmetric "bow-tie" pattern and was in the meridian
      corresponding to the superonasal and inferotemporal sclerotomies. All 5 of the
      patients requiring suture lysis had undergone repeat PPV through the same
      sclerotomies; all had their astigmatism reduced to an average of 1.5 D.
      CONCLUSION: Visually disabling astigmatism present months after surgery is almost
      certainly a rare, wound-related complication of PPV, but remains a previously
      unappreciated possibility in eyes undergoing repeat procedures through the same
      sclerotomies. Videokeratoscopy provides a reliable and rapid method of detection,
      while suture lysis in the steep axis represents a simple remedy.

PMID- 11820664
TI  - Bilateral retinal hemorrhages following automated lamellar keratoplasty.
AB  - We describe a case of bilateral multifocal retinal hemorrhages after receiving
      automated lamellar keratoplasty (ALK) surgery in a 32-year-old male with extremly
      myopic eyes. Before surgery, there was no retinal hemorrhage in routine fundus
      examination. This patient visited our clinic and complained of decreased vision
      in both eyes 2 weeks after the ALK surgery. Upon examination, his best-corrected
      visual acuity (BCVA) was 0.6 with -8.5-1.5 x 100(0) in the right eye and 0.9 with
      -4.0-2.50 x 90(0) in the left eye. Fundus examination revealed scattered multiple
      round focal retinal hemorrhages in both eyes. No evidence of choroidal
      neovascularization was noted. The retinal hemorrhages resolved 10 weeks later.
      The BCVA recovered to 1.0 in the right eye and 0.9 in the left eye. This case
      highlights the relationship between the postoperative bilateral posterior pole
      hemorrhages and the automated lamellar keratoplasty surgery, in which a
      microkeratome was used to create a corneal flap and keratectomy. Patients should
      be informed of this rare complication before surgery.

PMID- 11820665
TI  - Hyperbaric oxygen therapy for mitomycin C-induced scleral necrosis.
AB  - Intraoperative or postoperative use of mitomycin C is one of the treatment
      options to reduce the recurrence of pterygia. Scleral necrosis, a potentially
      blinding complication after mitomycin C use, has been among great concern in
      ophthalmic practice. A patient is presented in whom scleral necrosis developed 20
      days after a pterygiectomy with bare sclera technique was performed, followed by
      the application of 0.4 mg/mL of topical mitomycin C eye drops for 3 weeks. After
      conjunctival flap failures the patient was treated with hyperbaric oxygen
      therapy. The sclera revascularized and returned to near normal thickness after 24
      sessions of hyperbaric oxygen therapy. This case demonstrates that it is an
      effective, novel treatment. [Ophthalmic

PMID- 11820666
TI  - Combined iridocyclectomy and lensectomy surgical technique modified for the
      removal of an iris cyst in a child.
AB  - The purpose of this report is to describe a modified surgical iridocyclectomy
      technique and lensectomy for the removal of a recurrent iris cyst and a cataract
      in a child. A 3-year-old boy underwent uncomplicated standard iridocyclectomy for
      the removal of an enlarging congenital epidermal iris cyst. In the postoperative
      period, the cyst recurred. A second surgical intervention was performed using a
      modified iridocyclectomy technique. Sclerocorneal dissection of the involved
      quadrant was performed. After a lensectomy, an additional deep lamellar
      dissection of the peripheral cornea was undertaken prior to iris cyst removal and
      pupil reconstruction. This modified two-layered iridocyclectomy technique permits
      an elegant access to the iris lesion and allows the construction of a two-layered
      watertight wound, reducing the risk of hypotony and wound ectasia. We believe it
      also allows a better control of astigmatism and is a safe procedure in the
      pediatric population, particularly during the amblyogenic period.

PMID- 11820667
TI  - Iris prolapse in small incision cataract surgery.
AB  - Iris prolapse is a rare complication after small incision cataract surgery. We
      looked at the possible operative and perioperative factors that might have
      contributed to this complication in 2 of our patients and in another 10 patients
      identified through a national questionnaire survey. The details of 12 cases of
      iris prolapse following small incision cataract surgery are presented. Since iris
      prolapse may occur in small incision cataract surgery, notably in the presence of
      certain predisposing factors, extra diligence is required in wound construction
      and closure in high-risk patients.

PMID- 11820668
TI  - Acquired anterior ocular melanocytosis following cataract extraction.
AB  - The right eye of a 59-year-old man was the subject of extracapsular cataract
      extraction and posterior chamber lens implantation. He gradually developed
      superior sectoral scleral and diffuse iris hyperpigmentation within 7 years
      postoperatively. The iris was also uniformly thickened. He sustained 20/20 visual
      acuity in the pseudophakic eye. Despite marked pigmentation of the angle, his
      right intraocular pressure remained within normal limits. We use the term
      acquired anterior ocular melanocytosis because the pigmentary changes were
      confined to the anterior segment and the choroid was not involved. We conclude
      that surgical injury in the form of cataract extraction can induce
      episcleral/scleral hyperpigmentation and iris hyperchromia.

PMID- 11820669
TI  - Ophthalmoscopy and vitreoretinal surgery in patients with an ARRAY refractive
      multifocal intraocular lens implant.
AB  - We developed a clinical strategy for dealing with situations in which
      ophthalmoscopic examination and vitreoretinal surgery are difficult in patients
      with an ARRAY refractive multifocal intraocular lens (IOL) implant. The ARRAY
      zonal-progressive IOL has a central 2.1-mm distance-vision zone for optically
      unobstructed posterior pole observation. A concentric near-vision zone (+3.5
      diopter add) surrounds this central zone. Optical ray-tracing is used to
      determine how a 2.1-mm pupil limitation restricts monocular and binocular retinal
      image size in head-mounted, slit-lamp, and operating microscope ophthalmoscopy. A
      2.1-mm pupil decreases the retinal field of view of high magnification, narrow
      field lenses much more than that of wider-field, lower magnification lenses. This
      "worst-case" analysis suggests an ophthalmoscopic strategy, but is not strictly
      valid for the ARRAY lens because the near-vision zone surrounding its 2.1-mm
      central zone is not opaque. The near-vision zone contributes defocused
      information to the ophthalmoscopic image, diminishing its resolution and depth
      information. Wide-field, low magnification lenses are potentially less
      problematic than higher magnification lenses for examining and treating patients
      with an ARRAY IOL implant. This strategy is useful for panretinal
      photocoagulation or photodynamic therapy, but not for procedures requiring high
      magnification stereoscopic vision such as macular vitreoretinal surgery.

PMID- 11820670
TI  - Perfluorocarbon liquid assists in stripping the ILM to treat detached retina
      caused by macular hole.
AB  - Stripping the internal limiting membrane (ILM) is supposed to be beneficial in
      attaching the retina in retinal detachment because of macular hole. However, it
      is difficult to lift up and strip the ILM over extensively detached retinas
      because such retinas are very mobile. To evade this difficulty, we flattened the
      detached retina with perfluorocarbon liquid (PFCL) and peeled the ILM in the
      presence of PFCL. The ILM flap was easily turned up and enlarged with the
      posterior counter traction by PFCL. Intraoperative flattening of the retina with
      PFCL is useful in peeling the ILM from detached retinas.

PMID- 11820671
TI  - Surgical method and results of levator aponeurosis transposition for Graves'
      eyelid retraction.
AB  - Predictability of final eyelid height and contour following surgical correction
      of eyelid retraction remains problematic. We describe our surgical method and
      results with the distal levator aponeurosis transposition procedure for eyelid
      retraction. The procedure consists of disinserting the distal levator aponeurosis
      from the tarsal plate and excising Muller's muscle. The lateral three-fifths of
      the distal aponeurosis is fashioned into a flap that is disinserted laterally,
      rotated inferiorly 90 degrees, and attached to the tarsal plate. Distal levator
      transposition is useful in the management of dysthyroid retraction and in the
      reduction of the margin reflex distance (MRD) asymmetry between upper eyelids.
      However, it shares with other eyelid lowering procedures, the disadvantage of
      poor predictability of final MRD.

PMID- 11820672
TI  - Outcomes of bilateral macular hole surgery.
AB  - BACKGROUND AND OBJECTIVE: Characteristics and outcomes in patients undergoing
      macular hole surgery in both eyes are studied. MATERIALS AND METHODS: Demographic
      and clinical data were abstracted from patients' medical records for a
      retrospective study of 31 consecutive patients (62 eyes) who underwent macular
      hole surgery in both eyes between 1992-1998. Outcome measures included best
      corrected Snellen visual acuity and status of the macular hole 3 months after
      surgery. RESULTS: The duration of symptoms was 5.5 months at the time of surgery
      in the first eye and 9.8 months in the second operated eye (P= 0.063). The
      macular hole was closed after surgery in both eyes (17), only in the first eye
      (6), only in the second eye (6), and not closed in either eye (2) (P = 0.9)
      (46/62, 74% eyes overall). With reoperation 55/62 (89%) were closed. In eyes with
      a closed macular hole, the visual acuity improved 2 or more lines in 20 (88%)
      first eyes and 12 (52%) of the second eyes (P = 0.02). Cataract surgery was
      performed in 12 (41%) first eyes and 13 (45%) second eyes within 1 year of the
      initial macular hole surgery. The occurrence of cataract surgery in the second
      eye correlated with the first eye (P= 0.017). CONCLUSION: Macular hole surgery is
      usually successful in one or both eyes. Surgical results in the second eye do not
      appear to correlate with the results in the first eye.

PMID- 11820673
TI  - Gender and outpatient mental health service use.
AB  - The purpose of this study is to describe gender differences in the use of
      outpatient mental health services and to identify potential determinants of this
      use. The study sample, N = 7475 respondents 18-64 years, was drawn from the
      Mental Health Supplement to the Ontario Health Survey. For theoretical and
      empirical reasons, type of mental disorder was defined as: a Mood and/or Anxiety
      Disorder (Mood/Anx) or a Substance Use Disorder and/or Antisocial Behaviours
      (Subs/Asb) within the past year. Use was defined in relation to providers seen
      within the past year. Descriptive and multiple logistic regression analyses were
      employed including type of mental disorder, social and economic factors. Female
      gender remained positively associated with any use despite adjustments (adjusted
      OR: 1.7; 95% CI: 1.2: 2.4). The magnitude of this association was consistent
      across the levels of the study variables and various measures of use except
      volume of use where there were no gender differences. Mood/Anx appeared to
      mediate the gender-use relationship and was strongly associated with use
      (adjusted OR: 8.4; 95% CI: 5.9; 11.9). Subs/Asb was also related to use (adjusted
      OR: 2.6; 95% CI: 1.5; 4.3) but not to the same degree as Mood/Anx. Mood/Anx
      explained 60% of the crude Subs/Asb-use relationship. The evidence to suggest
      that Subs/Asb mediated the gender-use relationship was mixed. These findings
      raise questions about gender differences in illness and reporting behaviours and
      the health care system in its preferential treatment of women and those with
      Mood/Anx.

PMID- 11820674
TI  - Health-seeking behavior of Karachi women with reproductive tract infections.
AB  - To explore the contextual factors influencing health-seeking behavior of women in
      Karachi regarding reproductive tract infections, 18 women with reproductive tract
      infections from different clinics and community settings were identified and in
      depth interviews were conducted. Physicians in our study diagnosed a woman to
      have lower reproductive tract infection if she complained of malodorous vaginal
      discharge with or without perineal itching; and to have pelvic inflammatory
      disease or upper reproductive tract infection if she had any two of the following
      complaints: malodorous vaginal discharge, menstrual irregularities, lower
      abdominal pain or dyspareunia. Women consulted a variety of healthcare providers
      in their pursuit for treatment, mainly allopathic doctors and hakims. The
      different treatments prescribed to women ranged from oral and intravaginal
      medications to various home remedies including refraining from specific foods.
      Causes of reproductive tract infections reported were "melting bones", consuming
      foods with perceived hot composition, poor personal hygiene and procedures like
      dilatation and curettage, delivery and induced abortions. None reported sexually
      transmitted diseases as the perceived cause of their problem. Interference with
      religious activities, sexual relationships or socializing was reported as
      consequences of reproductive tract infections, in addition to lower abdominal
      pain, menstrual irregularities, backache and kamzori (weakness). Pakistani women
      seek care for reproductive tract infections and visit a variety of providers,
      though causes and treatments offered are usually not related to sexually
      transmitted diseases. We therefore suggest training of healthcare providers for
      appropriate counseling and that treatment management protocols be advocated.

PMID- 11820675
TI  - Listening to respondents: a qualitative assessment of the Short-Form 36 Health
      Status Questionnaire.
AB  - Standardised health status questionnaires are widely used to obtain subjective
      assessments of health. However, little research has investigated the meaning of
      the data they produce. Statistical tests will highlight some problems with the
      structure and wording of a questionnaire but they cannot shed any light on the
      way in which respondents interpret questions or their intended meaning when they
      select a response. Various qualitative techniques are being used within
      disciplines such as sociology and psychology to test both the language of survey
      instruments and the cognitive bases of surveys. This paper outlines some of these
      methods and reports findings from a qualitative research study in the UK with a
      widely used questionnaire--the Short-Form 36 Health Status Questionnaire. The
      value of including in-depth, qualitative validation techniques in the development
      and testing of surveys used to collect subjective assessments of health is
      clearly demonstrated by the findings of the study.

PMID- 11820676
TI  - Characterization of household food insecurity in Quebec: food and feelings.
AB  - This study was undertaken to understand food insecurity from the perspective of
      households who experienced it. The results of group interviews and personal
      interviews with 98 low-income households from urban and rural areas in and around
      Quebec City, Canada, elicited the meaning of "enough food" for the households and
      the range of manifestations of food insecurity. Two classes of manifestations
      characterized the experience of food insecurity: (1) its core characteristics: a
      lack of food encompassing the shortage of food, the unsuitability of both food
      and diet and a preoccupation with continuity in access to enough food; and a lack
      of control of households over their food situation; and (2) a related set of
      potential reactions: socio-familial perturbations, hunger and physical
      impairment, and psychological suffering. The results substantiate the existence
      of food insecurity among Quebecers and confirm that the nature of this experience
      is consistent with many of the core components identified in upstate New York.
      This study underlines the monotony of the diet, describes the feeling of
      alienation, differentiates between a lack of food and the reactions that it
      engenders, and emphasizes the dynamic nature of the experience.

PMID- 11820677
TI  - Compensating behaviors, regret, and heterogeneity in the dynamics of smoking
      behavior.
AB  - This paper studied smoking behavior in the context of the interactions among
      health, smoking, exercise and seeking medical care using a microeconomic model.
      Based on a dynamic optimal choice theory, a simultaneous equation system was used
      in the empirical estimation. This study found that smokers with longer smoking
      history tend to have extra incentives to maintain or improve their health. It was
      found that they tend to use more medical services and to be more active in
      exercise than smokers with shorter smoking history. Health status nonlinearly
      affects smoking decisions. Quitting incentives can be "curative" or "preventive",
      depending on one's health status. Light smokers' addiction is qualitatively and
      quantitatively different from heavy smokers'.

PMID- 11820678
TI  - HIV serostatus and factors related to physical and mental well-being in Latina
      family AIDS caregivers.
AB  - In a survey of 154 Latina AIDS caregivers living in Los Angeles, we examined
      differences in the stress process for those who were HIV seropositive,
      seronegative, and those with an unknown serostatus. Most caregivers were
      monolingual, poor, suffered from chronic physical illness unrelated to HIV, and
      received few services. All three subsamples reached clinical cut-off levels for
      depression on the brief symptom inventory. In the sample as a whole and in all
      three groups we examined differences in primary and secondary stressors as
      predictors of mental and physical well-being; differences in background factors
      as they relate to mental and physical well-being; and differences in predictive
      value of various factors that may attenuate the relationship between stress and
      mental and physical well-being. Models predicting both mental and physical well
      being differ across subsamples divided on the basis of serostatus. Based on these
      findings, we discuss implications for service provision designed to target these
      underserved Latina AIDS caregivers.

PMID- 11820679
TI  - Quality of registration of maternal deaths in Mozambique: a community-based study
      in rural and urban areas.
AB  - Maternal mortality is an important indicator used to assess the level of
      development of a country and particularly the coverage of health services. In
      Africa where the maternal mortality ratios are about 100 times higher than those
      of developed countries the situation is even worse due to problems of
      underregistration. In Mozambique the figures officially used are derived from the
      data of some hospitals in the main cities. This leaves out the 60% of pregnant
      women who do not attend health facilities. It was against this background that
      the present study was designed to be a prospective community-based study carried
      out in the central region of Mozambique involving a population of 207,369
      inhabitants. The study covered a 12-month period, from 01/08/96 to 31/07/97 and
      found 214 deaths among women in reproductive age (15-49 yr) of whom 40 were
      classified as maternal deaths. Gross underregistration was revealed, as the
      health institutions failed by 86% in recording maternal deaths, the same
      happening with other official sources, like the Civil Register and the Funeral
      Services registering only 9% of the maternal deaths. This kind of study is
      however complex and labour intensive and a practical way of monitoring has to be
      found; for the region where the study took place close collaboration with private
      cemeteries appears to be a way to be further explored.

PMID- 11820680
TI  - Cultural change and mental health in Greenland: the association of childhood
      conditions, language, and urbanization with mental health and suicidal thoughts
      among the Inuit of Greenland.
AB  - In Greenland, the rapid sociocultural change of the last 50 years has been
      paralleled by an epidemiological transition characterized by a reduction in
      infectious diseases, an increase in cancer and cardiovascular diseases, and an
      increased prevalence of mental health problems. During 1993-94 and 1997-98, two
      health interview surveys were conducted among Inuit in Greenland and Inuit
      migrants in Denmark. The response rates were 71 and 55%. Information on mental
      health was obtained from 1388 and 1769 adults. As indicators of mental health,
      the prevalence of potential psychiatric cases according to the General Health
      Questionnaire (GHQ-12) and the prevalence of suicidal thoughts were studied in
      relation to childhood residence and father's occupation, current residence, and
      language. The statistical methods included logistic regression and graphical
      independence models. The results indicated a U-shaped association in Greenland of
      GHQ-cases with age and a high prevalence of suicidal thoughts among young people;
      a low prevalence of GHQ-cases among those who were bilingual or spoke only
      Danish; and a high prevalence of suicidal thoughts among migrants who grew up in
      Denmark and among residents of the capital of Greenland. In Greenland, women were
      more often GHQ-cases and had suicidal thoughts more often than men. The
      association between language and GHQ-cases is presumed to operate through
      socioeconomic factors. It is necessary to modify the common notion that rapid
      societal development is in itself a cause of poor mental health: as a result of
      successful integration into the modern Greenlandic society, some population
      groups have better mental health compared to other groups.

PMID- 11820681
TI  - Health care for the elderly: two cases of technology diffusion.
AB  - Diffusion of medical technology and the growing proportion of elderly people in
      the population are generally regarded as major contributors to the increasing
      health care expenditure in the industrialised world. This study explores the
      importance of one specific factor in this process, the change in the use of
      technology among elderly patients. In some instances, a new technology is first
      used among younger patients and then gradually extended to the elderly. Two such
      cases are studied, both representing costly procedures: coronary bypass surgery
      (treatment of coronary heart disease) and dialysis (treatment of uraemia). In
      both cases, we demonstrate significant diffusion to older age groups. It is also
      tentatively concluded that the diffusion of technology could have an important
      effect on per capita health care expenditure among the oldest of the old.

PMID- 11820682
TI  - Metropolitan area income inequality and self-rated health--a multi-level study.
AB  - We examined the association of income inequality measured at the metropolitan
      area (MA) and county levels with individual self-rated health. Individual-level
      data were drawn from 259,762 respondents to the March Current Population Survey
      in 1996 and 1998. Income inequality and average income were calculated from 1990
      census data, the former using Gini coefficients. Multi-level logistic regression
      models were used. Controlling for sex, age, race, and individual-level household
      income, respondents living in high, medium-high, and medium-low income inequality
      MAs had odds ratios of fair/poor self-rated health of 1.20 (95% confidence
      interval 1.04-1.38), 1.07 (0.95-1.21), and 1.02 (0.91-1.15), respectively,
      compared to people living in the MAs with the lowest income inequality. However,
      we found only a small association of MA-level income inequality with fair/poor
      health when controlling further for average MA household income: odds ratios were
      1.10 (0.95-1.28), 1.01 (0.89-1.14), and 1.00 (0.89-1.12), respectively. Likewise,
      we found only a small association of county-level income inequality with self
      rated health although only 40.7% of the sample had an identified county on CPS
      data. Regarding the association of state-level income inequality with fair/poor
      health, we found the association to be considerably stronger among non
      metropolitan (i.e. rural) compared to metropolitan residents.

PMID- 11820684
TI  - Smoking and quitting: a qualitative study with community-living psychiatric
      clients.
AB  - This paper reports the findings of a study investigating the smoking behaviours
      of a community-based psychiatric population. Using a qualitative, grounded theory
      approach, the four diagnostic categories of schizophrenia, bi-polar affective
      disorder, depression, and personality disorder were studied (24 interviews in
      total) in order to identify similarities and differences in smoking behaviours
      and perceptions of links between illness and cigarette smoking. A number of
      theoretical constructs emerged from the data, many of which confirm and enhance
      current understandings of issues, such as the role of cigarettes in managing the
      symptoms of illness. However, several themes not found in the existing literature
      also emerged. Smoking was found to play a significant existential role in the
      lives of participants: alleviating the effects of stigma, promoting positive and
      negative freedoms, and providing core needs as part of quality of life decisions.
      Perceptions of the nature and degree of interaction between psychiatric symptoms
      and the 'need' to smoke were also found to be significant. Variations in smoking
      between the different diagnostic groups were also found, in particular in the
      process of smoking itself the nature of the nicotine dependence as predominantly
      physical or psychological, attitudes towards the quitting process and sense of
      control, and the degree of significance of existential factors. The research
      findings suggest that we may be able to add new methods to our current ways of
      intervening to assist people with a mental illness who want to quit smoking.
      Differences in perceptions and patterns of use suggest that intervention may be
      more effective if psychiatric diagnosis is also taken into consideration. Because
      the paper is descriptive and hypothesis generating, its findings need to be
      tested using a larger sample.

PMID- 11820683
TI  - An imperfect refuge: life in an 'old folk's home' for younger residents with
      psychiatric disorders.
AB  - Residents under age 65 comprise a small, but not insignificant, segment of the US
      nursing home population--a segment about which very little is known. This article
      explores the meaningful constitution of nursing home experience among younger,
      psychiatrically disabled residents of an urban nursing home. Residents' "behavior
      problems", the difficulties imposed by institutional life, and American age norms
      emerged as key dynamics in residents' understandings of nursing home life. In
      addition to these factors, the nursing home was evaluated in relation to previous
      life experiences, perceived alternatives, and expectations of personal freedom.
      Ultimately, most younger residents found the nursing home to be a refuge, albeit
      an imperfect one.

PMID- 11820685
TI  - Goal orientations, self-determination and pupils' discipline in physical
      education.
AB  - In this study, we examined the patterns of goal orientations, perceived
      competence, reasons for behaving well and self-reported discipline in school
      physical education among 511 pupils from years 8 and 9 (mean age 14.2 years).
      Cluster analyses were conducted on two randomly split subsamples to identify
      homogeneous groups of pupils on these measures of achievement motivation and
      discipline. Three meaningful clusters emerged for the first subsample, which were
      then cross-validated for the second subsample. One group of pupils revealed low
      scores on task and ego orientations, perceived competence and feelings of self
      determination about their behaviour in lessons. These perceptions were related to
      lower ratings of discipline in physical education than pupils who scored more
      highly on these variables. The highest discipline scores were reported by pupils
      with high task and ego orientations, perceived competence and feelings of
      autonomy. The results are useful for teachers and other physical activity leaders
      in enhancing motivation and disciplined behaviour in young people. Promoting more
      self-determined reasons for being disciplined, for example, could lead to more
      orderly classes.

PMID- 11820686
TI  - The physical activity, fitness and health of children.
AB  - It is clear that, despite their natural tendencies, children have become less
      physically active in recent decades, with children today expending approximately
      600 kcal days' less than their counterparts 50 years ago. Although the health
      consequences of a reduced energy expenditure in adults is well documented, there
      is little direct evidence linking sedentariness with health in children. However,
      three main benefits arising from adequate childhood physical activity have been
      postulated. The first is direct improvements in childhood health status; evidence
      is accumulating that more active children generally display healthier
      cardiovascular profiles, are leaner and develop higher peak bone masses than
      their less active counterparts. Secondly, there is a biological carry-over effect
      into adulthood, whereby improved adult health status results from childhood
      physical activity. In particular, childhood obesity may be a precursor for a
      range of adverse health effects in adulthood, while higher bone masses in young
      people reduce the risk of osteoporosis in old age. Finally, there may be a
      behavioural carry-over into adulthood, whereby active children are more likely to
      become more active (healthy) adults. However, supporting evidence for this
      assertion is weak. Given this background, recent health guidelines suggesting
      that children should accumulate 60 min of moderate-intensity physical activity
      every day--supplemented by regular activities that promote strength flexibility
      and bone strength--appear to be justified. Future developments should include the
      implementation of large-scale, longitudinal studies spanning childhood and young
      adulthood, the further refinement of tools for measuring physical activity
      accurately in young people, and research into the relative strength of
      association between fitness--as well as activity--and health in children.

PMID- 11820688
TI  - Towards an understanding of the personal experience of the 'yips' in cricketers.
AB  - The 'yips' is a phenomenon that affects individuals who perform finely controlled
      motor skills. The result is involuntary movements that occur throughout the
      execution of a skill. A qualitative study was conducted to identify the
      psychological characteristics of the 'yips' experience in cricket bowlers. Eight
      bowlers of varying ability were interviewed about their thoughts, emotions and
      feelings before, during and after their initial experience of the 'yips'. After
      the interviews, inductive content analysis revealed 15 general dimensions that
      were descriptive of the overall 'yips' experience: conditions before the initial
      experience, the first experience, anxiety, emotions and feelings, conscious
      control of movement, self-presentational concerns, inappropriate focus, negative
      thinking, future performances, reasons for not bowling, bowling experiences after
      the initial experience, the difference between the 'yips' and bowling badly,
      characteristics of good bowling performances, personal characteristics and
      personal explanations for why the 'yips' were experienced. We conclude that the
      experience of bowling with the 'yips' shows many characteristics similar to a
      severe form of choking.

PMID- 11820687
TI  - Beta-endorphin infusion during exercise in rats does not alter hepatic or muscle
      glycogen.
AB  - The aim of this study was to determine whether beta-endorphin infusion influences
      liver or muscle glycogen concentration during exercise. Thirty-two rats (Harlan
      Co., IN, USA) with a body mass of 265-290 g were assigned at random to four
      groups, each of eight rats: (1) beta-endorphin infusion for 90 min at rest; (2)
      beta-endorphin infusion for 90 min while running on a rodent treadmill at 22 m x
      min(-1) and 0% grade; (3) saline infusion (0.9% NaCl) for 90 min at rest; and (4)
      saline infusion for 90 min while running on a rodent treadmill at 22 m x min(-1)
      and 0% grade. Beta-endorphin infusion elevated plasma beta-endorphin
      concentration by 2.5-fold at rest compared with saline infusion at rest, and by
      two-fold after exercise compared with saline infusion after exercise. Beta
      endorphin infusion attenuated exercise-induced glucose concentration but did not
      alter the fasting hepatic glycogen concentration at rest or after exercise
      compared with saline infusion. Fasting hepatic glycogen decreased significantly
      as a result of 90 min of exercise independent of treatment. Deep intermedius
      muscle glycogen concentration at rest was similar after 90 min of both beta
      endorphin and saline infusion and decreased significantly as a result of 90 min
      of exercise independent of treatment. Our results suggest that liver and muscle
      glycogenolysis is not responsible for the differences in plasma glucose with beta
      endorphin infusion during exercise.

PMID- 11820689
TI  - The influence of crank rate on peak oxygen consumption during arm crank
      ergometry.
AB  - The aim of this study was to assess the influence of three imposed crank rates on
      the attainment of peak oxygen consumption (VO2peak) and other physiological
      responses during incremental arm crank ergometry. Twenty physically active,
      although non-specifically trained, males volunteered for the study. They
      completed an exercise protocol using an electrically braked arm ergometer (Lode
      Angio, Groningen, Netherlands) at crank rates of 60, 70 and 80 rev x min(-1). The
      order of tests was randomized and they were separated by at least 2 days. Peak
      VO2 was significantly higher (P < 0.05) at 70 and 80 rev x min(-1) than at 60 rev
      x min(-1). Peak ventilation volume increased as a function of crank rate and was
      higher (P < 0.05) at 80 than at 60 rev x min(-1). Peak heart rate was higher (P <
      0.05) at 70 and 80 rev x min(-1) than at 60 rev x min(-1). Furthermore, 70 and 80
      rev x min(-1) resulted in an extended test time compared with 60 rev x min(-1).
      The greater physiological responses observed during the tests at the two faster
      crank rates might have been the result of a postponement of acute localized
      neuromuscular fatigue, allowing for more work to be completed. We recommend,
      therefore, that an imposed crank rate between 70 and 80 rev x min(-1) should be
      used to elicit VO2peak and other physiological responses in arm crank ergometry.

PMID- 11820690
TI  - Ski jumping boots limit effective take-off in ski jumping.
AB  - In this study, we measured the vertical and horizontal take-off forces, plantar
      pressures and activation patterns of four muscles (vastus lateralis, gluteus
      maximus, tibialis anterior, gastrocnemius) in 10 ski jumpers in simulated
      laboratory conditions when wearing either training shoes or ski jumping boots. We
      found significant differences in vertical (P < 0.001), horizontal (P < 0.05) and
      resultant (P < 0.001) take-off velocities and vertical force impulse (P < 0.01).
      We found no significant differences in the jumpers' initial take-off positions;
      however, the jumping boots condition resulted in a smaller displacement in the
      final position of the following joint angles: ankle angle (P < 0.001), knee angle
      (P < 0.001), hip angle (P < 0.01) and shank angle relative to the horizontal (P <
      0.01). This corresponds with less electromyographic activity during take-off in
      both the gastrocnemius (300 to 200 ms and 200 to 100 ms before take-off) and
      gluteus maximus (300 to 200 ms and 100 to 0 ms before take-off). During the early
      take-off in the jumping boots condition, significantly more pressure was recorded
      under the heel (P < 0.001), whereas the forefoot was more highly loaded at the
      end of the take-off. Differences in take-off velocity (representing the final
      output of the take-off) can be accounted for in the main by the different use of
      plantar flexion, emphasizing the role of the knee and hip extensors when wearing
      jumping boots. We conclude that the stiffness of the structure of the jumping
      boots may result in a forward shift of pressure, thus limiting the effective
      vertical force. To avoid this pressure shift, the pattern of movement of
      simulated take-offs should be carefully controlled, particularly when wearing
      training shoes.

PMID- 11820691
TI  - Comparison of physiological responses to morning and evening submaximal running.
AB  - The aim of this study was to assess the effect of time of day on physiological
      responses to running at the speed at the lactate threshold. After determination
      of the lactate threshold, using a standard incremental protocol, nine male
      runners (age 26.3 +/- 5.7 years, height 1.77 +/- 0.07 m, mass 73.1 +/- 6.5 kg,
      lactate threshold speed 13.6 +/- 1.6 km x h(-1); mean +/- s) completed a
      standardized 30 min run at lactate threshold speed, twice within 24 h (07:00
      09:00 h and 18:00-21:00 h). Core body temperature, heart rate, minute
      ventilation, oxygen uptake, carbon dioxide expired, respiratory exchange ratio
      and capillary blood lactate were measured at rest, after a warm-up and at 10, 20
      and 30 min during the run. In addition, the rating of perceived exertion was
      reported every 10 min during the run. Significant diurnal variation was observed
      only for body temperature (36.9 +/- 0.9 degrees C vs 37.3 +/- 0.3 degrees C) and
      respiratory exchange ratio at rest (0.86 +/- 0.01 vs 0.89 +/- 0.07) (P < 0.05).
      Diurnal variation persisted for body temperature throughout the warm-up (37.1 +/-
      0.2 degrees C vs 37.5 +/- 0.3 degrees C) and during exercise (36.2 +/- 0.6
      degrees C vs 38.6 +/- 0.4 degrees C), but only during the warm-up for the
      respiratory exchange ratio (0.85 +/- 0.05 vs 0.87 +/- 0.02) (P < 0.05). The
      rating of perceived exertion was significantly elevated during the morning trial
      (12.7 +/- 0.9 vs 11.9 +/- 1.2) (P < 0.05). These findings suggest that, despite
      the diurnal variation in body temperature, other physiological responses to
      running at lactate threshold speed are largely unaffected. However, a longer warm
      up may be required in morning trials because of a slower increase in body
      temperature, which could have an impact on ventilation responses and ratings of
      perceived exertion.

PMID- 11820692
TI  - Clinical comparison of two intraocular pressure measurement methods: SmartLens
      dynamic observing tonography versus Goldmann.
AB  - PURPOSE: To compare intraocular pressure measurements obtained with SmartLens, a
      gonioscopic contact lens, to those from Goldmann applanation tonometry. METHODS:
      Eighty volunteers (20 healthy individuals and 60 glaucoma patients from the
      university eye hospital's outpatient department) were examined using conventional
      Goldmann tonometry and the new SmartLens tool. For each device three replicate
      measurements were performed. A paired t-test and the corresponding mean
      difference confidence interval approach were used to assess deviations in
      location of the two tonometric methods; the test procedure of Maloney and Rastogi
      was used for comparison of precision in paired data. Intraindividual differences
      were evaluated according to the approach of Altman and Bland. RESULTS: There was
      a mean difference of 5.6 mmHg (95% CI: 4.3 mmHg; 6.8 mmHg; P<0.01) in intraocular
      pressure between the two methods with a significant overestimation by SmartLens
      tonometry compared to Goldmann tonometry (P<0.01). The 95%-limits of agreement
      ranged from -5.4 mmHg to +16.6 mmHg for individual patients. The measurement
      method variance of SmartLens was higher (Maloney-Rastogi test; P <0.01). The mean
      coefficients of variation for intraindividual replicates were 10.1% (SmartLens)
      and 3.8% (Goldmann; P <0.01). CONCLUSIONS: Accepting Goldmann tonometry as gold
      standard for intraocular pressure measurement, the SmartLens method shows
      considerable variation and therefore is not proven to be an adequate substitute
      for Goldmann tonometry.

PMID- 11820693
TI  - Correlation of postoperative axial length growth and intraocular pressure in
      congenital glaucoma--a retrospective study in trabeculotomy and goniotomy.
AB  - BACKGROUND: This paper investigates the correlation of postoperative intraocular
      pressure (IOP) with axial length growth in children who underwent either
      trabeculotomy (TO) or goniotomy (GO) as primary surgery for congenital glaucoma.
      METHODS: Thirty-seven eyes of 21 children with congenital glaucoma who underwent
      one or two TOs from 1992 to 1997 and 26 eyes of 16 children with congenital
      glaucoma who underwent one or more GOs from 1974 to 1993 were retrospectively
      analyzed. None of the eyes had undergone other surgery previously. Thirteen of
      the TOs were combined with a small trabeculectomy. IOP was measured by handheld
      applanation tonometry (Perkins). Axial length was measured by ultrasound. The
      data were analyzed for correlation of postoperative IOP reduction with
      postoperative axial length growth. RESULTS: Mean duration of follow-up was 27.3
      months in the TO eyes and 37.1 months in the GO eyes. Mean pretreatment IOP
      before surgery was 28.4+/-6.9 mmHg in the TO eyes and 30.8+/-8.5 mmHg in the GO
      eyes. Mean IOP at the end of follow-up was 17.5+/-5.8 mmHg in the TO eyes and
      17.4+/-10.2 mmHg in the GO eyes. Axial length growth was normalized (proportional
      or slowed down compared with the nomogram of axial length growth) in 31 of the 37
      TO eyes and in 20 of the 26 GO eyes, and was increased in 6 of the TO eyes and 6
      of the GO eyes at the end of follow-up. Regarding axial length growth, 6 of 37 TO
      eyes had increased axial length growth at the end of follow-up. Three of these
      eyes also did not fulfill the IOP success criterion; 2 of the 3 eyes with
      normalized IOP had only borderline increased axial length growth. Six of 26 GO
      eyes had increased axial length growth at the end of follow-up. Five of these
      eyes did not fulfill the IOP success criterion; 1 eye with normalized IOP had
      only borderline increased axial length growth. CONCLUSION: The data show
      remarkably good correlation of postoperative IOP with postoperative axial length
      growth. Axial length measurements can therefore help to ascertain halting or
      progression of congenital glaucoma and thus are considered an important parameter
      for congenital glaucoma follow-up.

PMID- 11820694
TI  - Early angiographic changes after laser treatment of choroidal neovascularisation
      in age-related macular degeneration.
AB  - PURPOSE: To describe angiographic features detectable on fluorescein angiography
      (FA) and indocyanine green angiography (ICGA) early after laser photocoagulation
      of choroidal neovascularisation (CNV) in age-related macular degeneration (AMD).
      METHODS: Thirty-five eyes of patients with AMD and juxtafoveal or extrafoveal CNV
      referred to the angiographic centre of the Eye Clinic of Trieste were considered.
      Ophthalmological assessment included FA and ICGA performed 2 days before and 30
      min after laser treatment, and then 1, 2, 7, 14, 21 and 28 days after
      photocoagulation. Further clinical angiographic examinations were carried out 2,
      3, 4 and 6 months after treatment. Photocoagulation was performed for classic CNV
      on FA and occult CNV on FA, appearing as well-defined focal spot on ICGA.
      RESULTS: Our results show that interpretation of early post-treatment
      angiographic examinations may be awkward because diffuse leakage on FA and hot
      spots on ICGA are normally detectable soon after laser treatment and thereafter
      during the first 2 weeks. Later, at the 3-week control, leakage on FA and hot
      spots on ICGA are visible in 62.8% and in 37% of cases respectively; they
      disappear completely by the 4-week control. CONCLUSION: Difficulty in analysing
      FA and ICGA in the early post-photocoagulation period underlines the importance
      of the decision regarding when to perform the first reliable post-laser control
      and how to improve its interpretation. We suggest that the first angiographic
      control be performed 3 weeks after treatment, strictly monitoring those eyes
      showing leakage or marginal hot spots over the following weeks. Overlapping the
      post-laser hypofluorescent area on the pre-laser lesion can ensure the complete
      coverage of CNV, and analysis of the retinal and choroidal vascular pattern
      inside and near the photocoagulated area during the different angiographic
      phases, albeit difficult, is essential for the interpretation of the angiographic
      lesions.

PMID- 11820695
TI  - Effect of isovolemic hemodilution in central retinal vein occlusion.
AB  - BACKGROUND: Hemorheologic abnormalities have recently been shown to play a role
      in the pathogenesis of retinal vein occlusion (RVO), and several studies have
      demonstrated the efficacy of isovolemic hemodilution in these eyes. This study
      was designed to investigate further the effects of hemodilution, with regard to
      the duration of symptoms before the treatment. METHODS: In a prospective study,
      142 eyes with central or hemicentral RVO were treated by isovolemic hemodilution.
      The target hematocrit value was 35%. Mean duration of follow-up was 10 months. A
      subgroup of 50 patients treated within 2 weeks of the onset of symptoms was
      compared first with patients treated later by hemodilution, and then
      retrospectively with controls with central RVO and without hemodilution. RESULTS:
      Hemodilution therapy resulted in a decrease in hematocrit level from 42% to 32%
      on average, with no major side effect. After treatment, a significant decrease
      was observed in hemorheologic parameters (fibrinogen, erythrocyte aggregation),
      except in plasma viscosity. Retinal circulation times were significantly
      shortened. Visual acuity (VA) improvement immediately after treatment (in 43% of
      eyes) was correlated with better final visual outcome (P<0.05). At the end of
      follow-up, VA was better in patients treated within the first 2 weeks than in
      those treated later and in controls (41% had VA of 20/40 or more in the early
      treatment group versus 23% in the late-treatment group, P<0.01). Final retinal
      ischemia was also greater in the late-treatment group and in controls.
      Hemodilution in 12 patients with long-standing RVO and macular edema was
      ineffective. CONCLUSION: Our study is consistent with previous investigations
      that confirmed the efficacy of isovolemic hemodilution in RVO on hemorheologic
      parameters, retinal circulation times and final VA. It also underlined strongly
      the benefit of early treatment within the first 2 weeks of the RVO. Further
      studies are required to confirm these results.

PMID- 11820696
TI  - Application of visual evoked potentials for preoperative estimation of visual
      function in eyes with dense cataract.
AB  - PURPOSE: To determine whether the temporal frequency characteristics of the
      visual system as determined by visually evoked potentials (VEP) can be used for a
      preoperative estimation of the visual function in eyes with cataracts. METHODS:
      Light stimuli driven by a pseudorandom binary sequence (PRBS) of 40950 ms
      duration were presented and EEG recordings were made from 13 control and 20
      patients with cataracts preoperatively and 1 week after cataract operation. The
      first kernel of the PRBS-VEP was obtained as the first-order cross-correlation
      function between PRBS and PRBS-VEP. The Fourier transform of this function was
      used as the temporal frequency characteristic (TFC). RESULTS: The mean +/-
      standard deviation of the latency and amplitude of the VEP in normal controls
      were 110.8+/-4.3 ms and 2.01+/-0.67 microV, respectively. A high correlation
      (r>0.7) between the pre-and postoperative VEP waveform was obtained in 13 eyes
      (65%), and 14 eyes (70%) in the VEP-TFC curves. The sensitivity of the
      examination was 73%, 27%, and 91% for the latency, amplitude and TFC of the VEP,
      respectively. The specificity of the examination was 67%, 100%, and 89% for the
      same measures. Eleven of 12 eyes with abnormal TFC preoperatively showed retinal
      or optic nerve lesions postoperatively. False-negative results were seen in cases
      with delayed corneal edema. CONCLUSION: Postoperative visual function of patients
      with cataracts can be predicted by preoperative measurement of the TFC obtained
      by PRBS-VEP.

PMID- 11820697
TI  - External beam radiotherapy for age-related macular degeneration causes transient
      objective changes in tear-film function.
AB  - PURPOSE: Dry-eye symptoms have been described as possible radiation side effects
      after external beam radiotherapy for age-related macular degeneration. We
      therefore investigated tear-film function before and after treatment. METHODS:
      Thirty-nine patients with no apparent history of dry-eye symptoms were treated
      with a 6 MV linear accelerator using a 2x2 cm lateral field angled 10 degrees
      posteriorly. A total dose of 20 Gy, divided into 10 fractions of 2 Gy and
      administered 3 times a week, was delivered. Before and 1, 3, and 6 months after
      radiotherapy, tear secretion was measured by means of tear-film fluorophotometry.
      The fellow eyes served as controls. RESULTS: At baseline, mean tear secretion as
      measured by tear-film fluorophotometry was 7.15 microl/min in the eyes receiving
      radiation and 5.89 microl/min in the control eyes. No statistically significant
      differences were found between the two eyes at baseline (signed rank test). One
      month after treatment, again no significant differences could be found between
      the two eyes; 3 months after radiation, however, tear secretion was significantly
      lower in the irradiated eyes than in the fellow eyes (P=0.0017). Six months after
      treatment this effect could no longer be detected. CONCLUSION: External beam
      radiotherapy using 20 Gy in 10 fractions and a 2x2 cm lateral field causes a
      statistically significant difference in tear secretion 3 months after radiation.
      This effect seems to be transient, as it had disappeared in later follow-up
      examinations.

PMID- 11820698
TI  - Visual function after removal of subretinal neovascular membranes in patients
      with age-related macular degeneration.
AB  - BACKGROUND: Retinal pigment epithelial (RPE) cells have been transplanted to
      replace the RPE cells lost after surgical excision of choroidal neovascular
      membranes (CNV) associated with age-related macular degeneration. The purpose of
      this study was to analyze the visual function of eyes with altered RPE after
      surgical excision of choroidal neovascular membranes (CNV) associated with age
      related macular degeneration, and to determine the effect of proliferated or
      migrated RPE cells on visual function. METHODS: Forty-seven patients with age
      related macular degeneration underwent excision of CNVs following vitrectomy and
      tamponade with sulfur hexafluoride (SF6) or silicone oil. The appearance of pre-
      or subretinal fibrosis and pigmentation of the lesion was considered to indicate
      proliferation and migration of RPE cells. Microperimetry was also performed.
      RESULTS: A significant correlation was found between the size of CNVs removed by
      surgery and the size estimated by indocyanine green angiography (P=0.0126). The
      mean number of RPE cells lost was estimated at 1.52 x 10(4). Pre- or subretinal
      fibrosis or pigmentation was observed in 37 patients (75.5%). The number of eyes
      with fibrosis was significantly higher in eyes with silicone oil tamponade than
      with SF6 tamponade (P=0.0016). A statistically significant correlation was not
      found between the presence of fibrosis or pigmentation and the postoperative
      visual acuity. Not all patients used the area of pigmentation for fixation, and
      microperimetry showed that some of the patients had scotomas in well-pigmented
      areas. CONCLUSIONS: Fibrosis and pigmentation after excision of CNVs may not
      always indicate normal function in these areas. These observations are especially
      relevant for transplantation of pigment epithelial cells in the future.

PMID- 11820699
TI  - Heterophoria measured with white, dark-grey and dark-red Maddox rods.
AB  - BACKGROUND: Heterophoria is defined as a deviation from orthovergence position
      when no fusional contours are provided. It has been suggested that darkening one
      eye effects the phoric angle between the two eyes. We tested this assumption by
      comparing the phoric angles with white, dark-grey and dark-red Maddox rods.
      METHODS: In a first group of 14 subjects horizontal heterophoria was measured
      with white, dark-grey and dark-red Maddox rods. In a second group of 43 different
      subjects horizontal heterophoria was measured with white and dark-red Maddox
      rods. Subjects were asked to continually correct any perceived deviation, using
      Herschel prisms. Readings were taken after 1 min. RESULTS: Group 1 (n=14): No
      significant difference between white, dark-grey and dark-red Maddox rods
      (Friedmann test). Correlation between white and dark-grey Maddox rods r=0.97
      (P<0.0001), slope of regression line 0.92 (95% confidence interval 0.78-1.06).
      Correlation between white and dark-red Maddox rods r=0.94 (P<0.0001), slope of
      regression line 0.67 (95% confidence interval 0.53-0.82). Group 2 (n=43): No
      significant difference between white and dark-red Maddox rods (Wilcoxon signed
      rank tests). Correlation r=0.96 (P<0.0001), slope of regression line 0.95 (95%
      confidence interval 0.87-1.03). CONCLUSION: Our study revealed no significant
      difference and a high correlation among the phoric angles obtained with white,
      dark-grey and dark-red Maddox rods. The close match suggests that darkening one
      eye does not effect the phoric angle between the two eyes.

PMID- 11820700
TI  - Microcirculation in the macular area of eyes with an idiopathic epiretinal
      membrane.
AB  - PURPOSE: To measure the microcirculation in the macula area of eyes before and
      after the removal of an idiopathic epiretinal membrane (ERM) by vitreous surgery.
      METHODS: Tissue blood flow in the macula was examined with the Heidelberg retina
      flowmeter in 12 eyes with an ERM before and 3, 6, and 12 months after vitrectomy.
      Blood flow measurements were performed in a 10 x 5 degree area in the macula that
      was divided into superior and inferior areas. At least three measurements were
      obtained, and the mean blood flow (MBF) was calculated by scanning laser Doppler
      flowmetry. The ratio of the MBF in the affected eye to that in the fellow eye was
      used for statistical analysis. RESULTS: The ratios of the MBF in the affected to
      the fellow eye in the superior area before and 1, 3, 6, and 12 months after
      surgery were 0.73, 0.51, 0.77, 0.88, and 1.01, respectively. The ratios of the
      MBF in the inferior area for the same periods were 0.70, 0.52, 0.75, 0.83, and
      0.98, respectively. CONCLUSIONS: Eyes with an ERM showed abnormal hemodynamics in
      the macula that gradually improved after vitrectomy to a status comparable with
      the MBF of the normal fellow eye.

PMID- 11820701
TI  - Gene expression profile of ARPE-19 during repair of the monolayer.
AB  - BACKGROUND: The purpose of this study was to identify the profile of gene
      expression during retinal pigment epithelial (RPE) wound repair. METHODS: ARPE-19
      cells derived from a human RPE cell line were grown for 4 weeks and injured by
      creating multiple concentric wounds. Unwounded cultures served as controls.
      During the proliferative phase of wound repair, total RNA was extracted from
      control and wounded cultures, and a [32P]dATP-labeled cDNA probe was synthesized
      and hybridized to Atlas Arrays (Clontech, Palo Alto, Calif.) containing 588
      cDNAs. The autoradiograms obtained were then analyzed using the Molecular
      Dynamics software program. Semiquantitative PCR was carried out to confirm up
      regulation of four genes associated with wound repair. ELISA was performed to
      quantitate the secreted MCP-1. RESULTS: In wounded cultures prominent up
      regulation (greater than fivefold) was seen for genes encoding DNA synthesis and
      DNA repair proteins. A greater than threefold increase was seen for genes
      encoding mitogen-activated protein kinase, CD44, MCP-1 (monocyte chemotactic
      protein), thymosin beta-10, and HDGF (hepatoma-derived growth factor), among
      others. Genes encoding tumor suppressors were downregulated three- to five-fold
      in the wounded compared with the unwounded cultures. Semiquantitative PCR
      confirmed up-regulation of transcripts for thymosin beta-10, HDGF, CD44, and MCP
      1. ELISA showed a 20% increase in secreted MCP-1. CONCLUSIONS: Gene array
      analysis revealed a differentiation program that included increased expression of
      genes involved in wound repair (adhesion molecules, cytokines, signal
      transducers), along with increased MCP-1 secretion. The RPE may be an early
      participant in the inflammatory response that occurs with proliferative
      vitreoretinopathy.

PMID- 11820703
TI  - Studies on the feasibility of a subretinal visual prosthesis: data from Yucatan
      micropig and rabbit.
AB  - BACKGROUND: To estimate the feasibility of the subretinal concept of a visual
      prosthesis, animal models and prototypes, each representing a certain aspect of
      the final prosthesis, were utilised to test for requirements for such a medical
      device: (1) the ability to elicit--by electrical stimulation--event-related
      central activity in the central visual system, and (2) the long-term
      biocompatibility and biostability of the implant within the subretinal space.
      METHODS: (1) In rabbit and Yucatan minipig, cortical evoked potentials were
      recorded with chronically implanted epidural electrodes during stimulation with
      light flashes as well as during electrical stimulation in the subretinal space.
      Voltage pulses ranging from -3 V to +3 V were applied via an acutely implanted
      electrode array on a wired prototype. (2) For biocompatibility studies a silicon
      based micro-photodiode array (MPDA) was used that closely resembled the design
      and composition of the final prosthesis. Fourteen months after implantation,
      angiography was performed and the histological findings of the retina in the
      immediate vicinity of the implant were evaluated. RESULTS: (1) In both rabbit and
      minipig, subretinal electrical stimulation resulted in evoked cortical potentials
      that were comparable to visual evoked potentials. The lowest threshold levels for
      the subretinal stimulation were 0.6 V for rabbits and 2 V for minipigs. (2) Long
      term stability of an implanted MPDA and its biocompatibility were proven for a
      postoperative period of 14 months. CONCLUSIONS: Data from animal experiments with
      certain prototypes of the final prosthesis suggest the feasibility of the concept
      of a subretinal visual prosthesis: Both requirements were met: (1) the
      functioning of the subretinal stimulation and (2) the biocompatibility of the
      MPDA implant.

PMID- 11820702
TI  - Immunohistochemical and charge-specific localization of anionic constituents in
      pseudoexfoliation deposits on the central anterior lens capsule from individuals
      with pseudoexfoliation syndrome.
AB  - BACKGROUND: Pseudoexfoliation (PSX) syndrome is a degenerative systemic disorder
      that is characterized primarily by deposits of distinct fibrillar material on the
      surface lining the anterior and posterior chambers of the eye and is often
      associated with cataract and glaucoma. Although some components of the PSX
      material have been identified, the precise composition is obscure. METHODS: High
      resolution scanning electron microscopy in conjunction with colloidal cationic
      gold labeling was used to localize anionic constituents at the surface of PSX
      aggregates. Transmission electron microscopy was applied for the
      immunocytochemical detection of glycosaminoglycans, and to monitor the charge
      specific distribution of colloidal thorium dioxide and ferritin in PSX material.
      The specific binding of antibodies was confirmed by immunohistological staining
      of paraffin-embedded specimens. RESULTS: Paraffin-embedded tissue sections
      revealed immunoreactivity for keratan sulfate and dermatan sulfate proteoglycan
      within PSX material deposited on the surface of the anterior lens capsule. Post
      embedding immunogold labeling of keratan sulfate demonstrated an intense label of
      PSX aggregates primarily associated with mature PSX fibrils, whereas dermatan
      sulfate proteoglycon appeared to be present in low quantities. Additionally,
      keratan sulfate was found at the humoral periphery of the lens capsules. To
      further investigate the distribution of anionic sites in PSX material, we used
      cationic colloidal tracers of different size, such as gold, thorium dioxide and
      ferritin. PSX aggregates exhibited a strong negative charge, resulting very
      likely from glycosaminoglycan chains of proteoglycans. The density of anionic
      sites was higher at the interfibrillar matrix. Lens capsules associated with PSX
      material revealed a diminished accumulation of cationic ferritin at the humoral
      surfaces. CONCLUSIONS: Increased amounts of different glycosaminoglycans
      identified in PSX material suggest an important role of proteoglycans for the
      pathogenic pathway in PSX.

PMID- 11820704
TI  - Three-dimensional ultrasound findings of the posterior iris region.
AB  - PURPOSE: The aim of this study was to assess the benefit of the three-dimensional
      ultrasound biomicroscopy in examination of the posterior iris and ciliary body.
      METHODS: Three-dimensional visualisation of the anterior eye section was achieved
      through extension of the existing ultrasound biomicroscope system (Humphrey
      Instruments). Visualisation of posterior iris and ciliary body pathologies in
      three patients was performed with a three-dimensional reconstruction technique of
      B-scans. RESULTS: The extended ultrasound system provided three-dimensional
      visualisation of alterations of the posterior iris region, i.e. iris cysts,
      ciliary body cysts and solid tumours of the ciliary body and iris. CONCLUSIONS:
      The three-dimensional ultrasound biomicroscopy yields extended diagnostic
      findings regarding iris and ciliary body pathology. This method offers an
      improved assessment of the posterior surface of the iris and the volume of the
      ciliary body. Furthermore, these data can be useful for procedures in computer
      simulation and calculation for a better understanding of the function of the
      ciliary body in the accommodation process.

PMID- 11820705
TI  - Vascular plasticity--the role of the angiopoietins in modulating ocular
      angiogenesis.
AB  - Most of the blinding diseases, such as diabetic retinopathy, age-related macular
      degeneration, neovascular glaucoma or trachoma, are related to an aberrant
      angiogenic response. Common pathological features are ischaemia and increased
      vascular permeability, in turn leading to neovascularization or atrophy. Recent
      effort has led to the identification of several factors, such as the angiopoietin
      Tie system, which are operative in the control of vasculogenesis and
      angiogenesis. The aim of this commentary is to summarize briefly the current
      knowledge about molecular mechanisms involved in the regulation of vascular
      integrity with special emphasis on the angiopoietins.

PMID- 11820706
TI  - The gastrointestinal tolerability of bisphosphonates.

PMID- 11820707
TI  - Tolerability of risedronate in postmenopausal women intolerant of alendronate.
AB  - Bisphosphonates are effective treatments for osteoporosis, but some have been
      associated with upper gastrointestinal intolerance. This randomized, double-blind
      study assessed the upper gastrointestinal tolerability of risedronate in
      postmenopausal women who had discontinued alendronate treatment because of upper
      gastrointestinal adverse events. Sixty-six women who had previously discontinued
      treatment with alendronate 10 mg/day because of upper gastrointestinal symptoms
      received placebo (N=31) or risedronate 5 mg (N=35) daily for 3 months. The
      primary outcome was the rate of discontinuation due to upper gastrointestinal
      adverse events: 5/31 (16.1%) in the placebo group, and 4/35 (11.4%) in the
      risedronate group. Discontinuation rates were also similar in the two treatment
      groups among subgroups of patients with a history of gastrointestinal disorder,
      prior use of acid suppression drugs, and concomitant use of NSAIDs. The overall
      incidence of upper gastrointestinal events was comparable between the placebo
      (19.4%) and risedronate (20.0%) groups. Overall, risedronate 5 mg/day for 3
      months was as well tolerated as placebo in patients who could not tolerate
      alendronate 10 mg. These results are consistent with, and complement those from
      previous studies showing that risedronate 5 mg has a gastrointestinal
      tolerability similar to that of placebo.

PMID- 11820708
TI  - Assessing pain and pain relief in geriatric patients with non-pathological
      fractures with different rating scales.
AB  - Although pain is a frequent problem among elderly patients, they are often
      omitted in clinical trials and few studies have focused on assessing pain relief
      in this population. The aim of this study was to compare geriatric patients'
      verbally reported effect of analgesics with changes in pain experience rated with
      four different rating scales: the Visual Analogue Scale (VAS), the Graphic Rating
      Scale (GRS), the Numeric Rating Scale (NRS), and the Pain Relief Scale (PRS).
      Altogether 53 geriatric patients (mean=82 yrs) with non-pathological fractures in
      4 geriatric units at a large university hospital were selected. In connection
      with the administration of analgesics, the patients were asked to "Mark the point
      that corresponds to your experience of pain just now at rest" on the VAS, GRS and
      NRS. This was repeated after 1.5-2 hours, and a direct question was asked about
      whether the analgesic medication given in connection with the initial assessment
      had had any pain-alleviation effect. Two comparisons were conducted with each
      patient. The results show that the probability of accomplishing a rating on the
      VAS, GRS, NRS, and PRS was lower with advancing age in these elderly fracture
      patients. The correlations between the ratings of the VAS, GRS and NRS were
      strong and significant (r=0.80-0.95; p<0.001) both at the initial assessments and
      at the re-assessments. However, the verbally reported effects of the analgesics
      were often directly opposite to the changes in rated pain. Therefore, application
      of the VAS, NRS, GRS and PRS for the purpose of assessing pain relief must be
      combined with supplementary questions that allow the patient to verbally describe
      possible experience of pain relief.

PMID- 11820709
TI  - Measuring general health status in dementia: practical and methodological issues
      in using the SF-36.
AB  - The objective of this study was to examine the measurement properties of the
      Medical Outcomes Study (MOS) 36-Item Short-Form health survey (SF-36) in a
      representative sample of dementia patients. A total of 138 subjects with dementia
      were evaluated with the SF-36. They were recruited from 16 centers, including 7
      university hospital centers. Dementia severity, demographic variables, co
      morbidity and functional limitations were also measured. The measurements
      obtained were compared by source of information (patient, family proxy, and care
      provider proxy). Thirteen patients refused to complete this questionnaire. Help
      from the interviewer was necessary in 72.8% of the cases. The average completion
      time was 18.8 minutes. Missing data exist in only 5.6% of the cases on average,
      except among patients with severe dementia (Mini Mental State Examination <10).
      With regard to reliability, internal consistency was acceptable to good;
      Cronbach's a ranged from a low of 0.59 to a high of 0.92 across subscales (median
      0.75). Test-retest intraclass correlation coefficients were moderate to good
      (range 0.51-0.81) except for Role emotional (0.17), Bodily pain (0.49) and Mental
      health (0.45). For patients with MMSE > or = 15, test-retest coefficients were
      better (range 0.53-0.90). Intraclass correlation coefficient suggests that
      proxies are a poor substitute for obtaining a patient's perspective of his/her
      health status. In conclusion, the SF-36 is unsuitable for severe dementia,
      because severity of disease mainly affected the feasibility, acceptability, and
      reproducibility of the instrument. This study, however, confirms that it is
      possible to question subjects with mild to moderate dementia on their health
      status.

PMID- 11820710
TI  - Nutritional status and chewing capacity in nursing home residents.
AB  - Chronically ill elderly persons sustain a high risk for protein-energy
      malnutrition (PEM). In this study we explored some of the complex associations
      between nutritional status, dental health and cognitive and physical function in
      192 nursing home residents (mean age 84+/-8 years, 80% female). Nutrition-related
      data from the Resident Assessment Instrument (RAI) were compiled into a Nutrition
      Score (NuSc; 0-1 = non-PEM, 2 = risk for PEM, and 3-7 = PEM). Chewing capacity,
      according to number and condition of occlusal contacts, was determined by a
      Clinical Dental Functionality score (CDF). The Cognitive Performance Scale (CPS)
      and activities of daily living (ADL) were determined according to the RAI. Fifty
      percent of the residents had NuSc > or = 2, and 25% had NuSc > or = 3. One third
      did not have the dental prerequisites for chewing. i.e., < 4 occlusal contacts.
      Almost half of the residents had severe cognitive dysfunction, and over two
      thirds were severely limited in their ADL activities. Subjects with > or = 4
      occlusal contacts, i.e., technical chewing capacity, had better NuSc (1.5+/-1.4)
      than those not able to chew (2.4+/-1.6, p=0.0005). In univariate logistic
      regression, the odds for NuSc > or = 2 increased with reduced ADL functions.
      inability to chew and poor cognition. In multivariate logistic regression, ADL
      and chewing capacity were significantly related to NuSc > or = 2. When NuSc > or
      = 3 was chosen as cut-off, only ADL was related to malnutrition. In conclusion,
      half of this group of nursing home residents appeared to be malnourished, or were
      at risk for PEM. Reduced physical function was the strongest predictor of PEM,
      while impaired chewing capacity was associated with risk for PEM.

PMID- 11820711
TI  - Orthostatic hypotension in elderly women with congestive heart failure.
AB  - Orthostatic hypotension is common in the elderly and could be the cause of
      impaired vision, dizziness, fainting spells and falls. To date, studies on
      orthostatic hypotension have chiefly concentrated on elderly patients in nursing
      homes, outpatients or healthy subjects. Congestive heart failure (CHF) is one of
      the most common causes of hospitalization and pharmacotherapy in the elderly, but
      little is known about the orthostatic hypotension in patients with CHF. The aim
      of this study was to evaluate the prevalence of orthostatic hypotension and
      associated symptoms in elderly females hospitalized for CHF. The study group
      included 36 women aged 70-100 years (mean 82.2), admitted to hospital for
      congestive heart failure. The control group consisted of 15 women aged 71-95
      years (mean 82.5) with no symptoms of heart failure or other diseases, who
      underwent earlier epidemiological studies on Cracow's elderly population. In all
      subjects a tilt test was performed (60 degree tilt for 10 minutes) under
      standardized conditions (fasting patients, 12 hours after the last administration
      of medications, between 8:00 and 10:00 a.m.). Orthostatic hypotension was defined
      as a decline of 20 mmHg or more in systolic blood pressure, or 10 mmHg or more in
      diastolic blood pressure on assumption of the upright position. Orthostatic
      hypotension was detected in 83.3% of CHF women, and 43.3% of them manifested
      clinical symptoms associated with it. In the control group, orthostatic
      hypotension was noted in 53.3% of women, but none was symptomatic. In particular,
      the CHF patients showed a decreased ability to develop compensatory tachycardia
      during hypotension. Moreover, reduction in systolic blood pressure was more
      pronounced in CHF patients, and diastolic blood pressure increase was less
      significant as compared with the control group.

PMID- 11820712
TI  - Validation of the functional fitness age (FFA) index in older Japanese women.
AB  - Functional fitness age (FFA), which we previously described, is a measure of
      functional age that reflects a person's overall physical ability to complete
      daily tasks such as preparing meals and performing various household chores. The
      purpose of this study was to validate FFA in two elderly populations: 1) older
      subjects from different communities, and 2) older subjects participating in an
      exercise intervention program. FFA was calculated from 4 performance tests:
      performing arm curls; moving beans with chopsticks; demonstrating functional
      reach; and sitting and walking around two cones. The first study group was
      selected from 4 different communities (N=127), and was subdivided into a less
      active group (N=87) and an active group (N=40). The results of the 4 tests for
      the less active group were not significantly different from those for the
      original validation group used in developing the FFA equation. The FFA of the
      less active group (71.1+/-7.7 yrs) was not different from their chronological age
      (70.4+/-6.6 yrs). In the active group, except for the arm curls, test scores were
      significantly higher than those of the original validation group. The FFA of the
      active group (66.2+/-5.1 yrs) was significantly younger than their chronological
      age (70.9+/-4.2 yrs). Another group of 14 older women (79.5+/-3.9 yrs) was
      recruited for pre- and post-training testing. After the 3-month exercise program,
      they showed significant improvements in sitting and walking around two cones and
      functional reach; their FFA decreased significantly from 81.5+/-5.0 yrs to 78.3+/
      4.5 yrs. The control group selected from the same community (N=16, 79.8+/-5.3
      yrs) showed no significant changes in the 4 performance tests, and their FFA
      remained unchanged. These results indicate that our FFA is highly cross-validated
      for different Japanese communities, and is sensitive to changes associated with
      participation in an exercise intervention program.

PMID- 11820713
TI  - Does nutritional supplementation influence the voluntary dietary intake in an
      acute geriatric hospitalized population?
AB  - Undernutrition is a significant problem in hospitalized elderly patients, and is
      associated with a higher morbidity and mortality. The aim of this study is to
      assess the effect of an oral nutritional supplementation on the total daily
      caloric intake in an acute geriatric hospitalized population. A dietary
      assessment and a total food intake were collected on admission and every other
      day (day 0, 2, 4, 6 ...) during hospitalization (mean duration, 12.8 days+/-6) in
      50 randomly chosen elderly patients (mean age 82.5+/-5.5 years, 18 men and 32
      women). The mean daily caloric intake was calculated from 108 dietary assessments
      after receiving oral supplementation (Nutridrink-Nutricia, 300 kcal/200 mL), and
      154 when a voluntary diet without supplementation was consumed. The mean
      voluntary energy intake (including parenteral fluid) was similar on days a
      nutritional supplementation was given or not (1546 kcal/d vs 1475 kcal/d,
      respectively, p=0.27), but the total caloric intake was significantly higher on
      days a nutritional supplementation was consumed (1825 kcal/d vs 1475 kcal/d,
      p=0.0006). This beneficial effect of a nutritional supplementation on the total
      caloric intake existed when patients were divided into well nourished (N=15) and
      those at risk or malnourished (N=35), according to the Mini-Nutritional
      Assessment. In conclusion, short-term nutritional supplementation has a
      beneficial effect on the total daily caloric intake in elderly hospitalized
      patients with and without malnutrition, but the wastage remains high.

PMID- 11820715
TI  - Postmortem examinations in patients of a geriatric hospital.
AB  - The rate of postmortem examinations (PME) especially in elderly patients is
      continuously declining, mostly due to the low interest of the medical staff and
      the reluctance of relatives. We surveyed PME performed over a 20-year period in
      patients of a geriatric hospital in Israel. The 93 autopsies represent a rate of
      2.8% in the first five years which went down to 0.25% in the later years. In 58%
      of the cases, clinical cause of death was confirmed by the PME. Pulmonary
      embolism had the lowest confirmation rate, and was more frequently found in
      females (28%) than in males (10%) (p<0.03). Undiagnosed conditions in the elderly
      present a clinical challenge that increases with the patient's age. However,
      despite progress in diagnostic technology, confirmation rates of death causes
      have not changed much. Therefore, as the age of death rises, it is important to
      preserve and foster PMEs, the most reliable source of medical evidence.

PMID- 11820714
TI  - Effectiveness of geriatric evaluation and care. One-year results of a multicenter
      randomized clinical trial.
AB  - The aim of this study was to demonstrate the effectiveness of outpatient elderly
      care based on Comprehensive Geriatric Assessment (CGA). Eleven hospital Geriatric
      Evaluation and Management units (GEMs) systematically screened 1386 inpatients
      over a 10-month period, using the same uniform selection plan which included 15
      programmed exclusion-inclusion criteria and a standard CGA. At the end of this
      screening, 152 eligible frail elderly patients were randomized to either a
      comprehensive outpatient GEMs program (intervention group: N=79) or to usual care
      by their family doctors (control group: N=73). We did not find any statistically
      significant difference between the two groups at entry. During the one-year
      follow-up period, 6 GEMs patients (7.6%) and 12 controls (17.1%) died, without
      significant differences between the two survival curves. Only three patients (all
      controls) ultimately dropped out, and eight (3 unit patients and 5 controls)
      entered a nursing home. GEMs patients were significantly more likely to have
      individual improvement in mental status (p=0.006), morale (p=0.024) and
      functional level (p=0.023), compared to controls. Even though intervention
      participants spent fewer days in hospital and nursing home (p<0.05), they
      received much more home care and day-hospital assistance (p<0.001), which
      explains why total expenditure on health care was the same in the two groups. We
      conclude that: 1) a standardized selection plan may contribute to identify the
      older inpatients in need of CGA; and 2) CGA-based outpatient care may be clinical
      and cost-effective if directly managed by GEMs, and may provide targeted older
      patients with more substantial benefits than standard care, without inflating
      health care expenses.

PMID- 11820716
TI  - Immunohistochemistry and reverse transcriptase polymerase chain reaction on
      sentinel lymph nodes can improve the accuracy of nodal staging in breast cancer
      patients.
AB  - In this study the nodal staging sensitivity of sentinel lymph node biopsy (SLNB)
      with detailed pathological and molecular biological examination has been
      investigated and compared to that of axillary lymph node dissection (ALND) with
      routine histological evaluation. Sentinel lymph nodes (SLNs) were removed by the
      dual-agent injection technique in 68 patients with primary, clinically node
      negative breast cancer. Forty-seven patients had negative SLNs according to
      hematoxylin and eosin (H&E) staining. These H&E-negative SLNs were serially
      sectioned and examined at 250 microm levels by anticytokeratin
      immunohistochemistry (IHC). In 14 patients the SLNs were also investigated by
      cytokeratin 20 (CK20) reverse transcriptase polymerase chain reaction (RT-PCR).
      SLNB with IHC increased the node-positive rate by 26% (by 40% in tumors less than
      or equal to 2 cm in size (pT1) and by 9% in tumors more than 2 cm but less than
      or equal to 5 cm in size (pT2)). The sensitivity of SLNB with IHC was superior to
      that of ALND with routine histology in pT1 tumors and identical in pT2 tumors.
      The concordance between histology and RT-PCR was only 21%, and in two of three
      cases with positive histological results RT-PCR was negative. In conclusion, SLNB
      with detailed pathological and/or molecular biological evaluation can improve the
      sensitivity of regional staging. ALND can probably be abandoned in patients with
      pT1 SLN-negative breast cancer. Further prospective studies are required to
      determine the clinical significance of these detailed SLN evaluation techniques,
      but at present these methods are still investigational.

PMID- 11820717
TI  - Soluble urokinase plasminogen activator receptor measurements: influence of
      sample handling.
AB  - AIM: The influence of sample handling on soluble urokinase plasminogen activator
      receptor (suPAR) concentrations in serum and EDTA plasma was studied in 16
      healthy premenopausal women. METHOD: Blood was collected in dry tubes and tubes
      containing EDTA and kept at 4 degrees C or 20 degrees C for 1, 3, 8, 24 or 72
      hours before processing into serum or EDTA plasma. In addition, serum and EDTA
      plasma were frozen and thawed 1-8 times. All suPAR measurements were performed by
      ELISA. RESULTS: No significant differences were found between serum or EDTA
      plasma suPAR concentrations when whole blood samples were kept for 1, 3, 8 or 24
      hours. Significantly higher suPAR levels were found in samples kept for 72 hours
      at 20 degrees C compared to samples processed into serum or EDTA plasma after
      short-term storage for no more than 24 hours after collection. No significant
      differences were observed when whole blood was kept at 4 degrees C for up to 72
      hours. Repeated freezing and thawing had no significant effect on the serum and
      EDTA plasma suPAR levels. CONCLUSION: suPAR values in blood samples are dependent
      on the handling procedures of the samples. All samples of whole blood must be
      processed into EDTA plasma or serum within 24 hours if kept at 20 degrees C and
      within 72 hours if kept at 4 degrees C. However, repeated freezing/thawing cycles
      had no influence on suPAR values in the samples.

PMID- 11820718
TI  - Immunohistochemical study of pepsinogen C expression in cutaneous malignant
      melanoma: association with clinicopathological parameters.
AB  - BACKGROUND: The aim of this study was to evaluate the pepsinogen C expression in
      malignant cutaneous melanomas and analyze its possible relationship to clinical
      and pathological parameters. Pepsinogen C is an aspartyl proteinase primarily
      involved in the digestion of proteins in the stomach and represents one of the
      main androgen-inducible proteins in breast cancer cells. METHOD: Tumoral
      pepsinogen C expression was retrospectively analyzed in 35 paraffin-embedded
      tissues from patients with primary malignant cutaneous melanoma and in 10 samples
      from 10 benign lesions (4 dermal melanocytic nevi, 4 compound melanocytic nevi
      and 2 dysplastic melanocytic nevi), using immunohistochemical methods. RESULTS:
      The benign lesions were consistently negative for pepsinogen C, whereas 20 of the
      35 malignant melanomas (57%) showed positive immunostaining for pepsinogen C. The
      percentage of pepsinogen C-positive tumors was significantly higher in men than
      in women (p=0.01) and in epithelioid melanomas than in fusocellular or mixed type
      melanomas (p=0.003). In addition, the percentage of pepsinogen-C positive tumors
      was positively and significantly correlated with lesion thickness (p=0.003),
      Clark's level of invasion (p=0.028) and tumor stage (p<0.001). CONCLUSION:
      Pepsinogen C could be a new prognosticator of unfavorable outcome in cutaneous
      malignant melanoma.

PMID- 11820719
TI  - Differential expression levels of urokinase-type plasminogen activator and
      cathepsin D in locally advanced laryngeal squamous cell carcinoma: clinical
      implications.
AB  - The expression levels and the prognostic impact of urokinase-type plasminogen
      activator (uPA) and cathepsin D (CD) were evaluated in patients with locally
      advanced laryngeal squamous cell carcinoma (LSCC). uPA and CD protein levels were
      determined by immunoluminometric or immunoenzymatic assays in the cytosol of
      paired sets of tumor tissues and corresponding adjacent normal mucosa (NLM) from
      57 patients with stage III/IV LSCC and were correlated with a number of
      clinicobiological parameters of this tumor including anatomical site, tumor
      grade, nodal status, clinical stage, DNA ploidy, proliferation rate, and patient
      outcome. Median uPA levels were significantly higher in LSCC than in NLM (1.8
      ng/mg of protein vs 0.3 ng/mg; p<0.001) whereas median CD levels were not
      significantly increased in tumor tissue compared to NLM (24 pmol/mg vs 19
      pmol/mg, p=0.063). No significant correlation was observed between uPA and CD
      concentrations in tumor tissues (r=-0.1; p=0.4). Furthermore, the distribution
      analysis of uPA and CD in tumors showed no correlation between expression levels
      of these proteinases and the parameters mentioned above including patient
      outcome. However, when data were matched according to each parameter examined it
      was observed that the differences in uPA content between LSCC and NLM, expressed
      as uPA tumor/normal tissue ratio (T/M), were more marked in clinically advanced
      and/or aggressive forms of LSCC (i.e., node positive, stage IV, poorly and
      moderately differentated, aneuploid multiclonal, low S-phase, subglottis tumors).
      These data suggest that in such tumors altered regulation of uPA may occur to a
      greater extent than in less aggressive and less advanced forms of LSCC. This
      phenomenon was not observed for CD. However, in tumors with a high proliferation
      rate, in stage IV tumors as well as in those located in the supraglottis, CD
      levels were significantly higher than those found in the corresponding NLM
      (p=0.008, p=0.02 and p=0.03, respectively). In conclusion, uPA is highly
      expressed in locally advanced LSCC and appears to be implicated in some key
      events of progression of this tumor such as local invasion and/or nodal
      involvement, whereas CD does not seem to have a role in promoting these
      processes. Nevetheless, neither of these proteinases seem to be prognostically
      useful in patients with stage III/IV tumors.

PMID- 11820721
TI  - Evaluation of HER-2/neu in serum and tissue of primary and metastatic breast
      cancer patients using an automated enzyme immunoassay.
AB  - Serum HER-2/neu concentrations were evaluated in 172 healthy subjects, 176
      primary and 55 metastatic breast cancer patients, employing a new automated assay
      (Bayer Immuno 1 serum HER-2/neu). Using 13 ng/mL as the cutoff, abnormal HER
      2/neu serum levels were found in 8% (14/176) of primary and 50.9% (28/55) of
      metastatic breast cancer patients. Both in primary and metastatic breast cancer a
      significant relationship was found with the stage of the disease when serum HER
      2/neu was considered as a categorized variable (p=0.0003 and p=0.02,
      respectively), but not when it was taken as a continuous variable (p=0.247 and
      p=0.146, respectively). Moreover, we evaluated the correlation between Immuno 1
      HER-2/neu and Oncogene Research Products ELISA assay in 53 normal subjects, 46
      primary and 34 metastatic breast cancer patients. The correlation was relatively
      good (p<0.0001), although substantial differences could be found in single cases.
      The Immuno 1 assay was also evaluated for the first time in breast cancer tissue.
      The method, which showed good performance both in terms of imprecision and
      linearity, was used to measure HER-2/neu protein in 140 cytosol samples from
      primary breast cancer tissue and in homogenates from 40 matched cases. The
      correlation between the two matrixes was very close (p<0.0001). By contrast, no
      correlation was found between serum and matched cytosol (p=0.101) or homogenate
      samples (p=0.511).

PMID- 11820720
TI  - C-erbB-2 oncoprotein in gastric carcinoma: correlation with clinical stage and
      prognosis.
AB  - The aim of this study was to investigate the expression of the oncogene c-erbB-2
      in gastric tumors. Immunohistochemical study of the expression of c-erbB-2 was
      performed in formalin-fixed, paraffin-embedded sections from 82 gastric
      adenocarcinomas using polyclonal antibody. c-erbB-2-positive immunostaining was
      observed in 37 (45%) tumors. Positive staining was detected in 63% of well
      differentiated, 46% of moderately differentiated and 80% of papillary
      adenocarcinomas. In poorly differentiated adenocarcinomas, positivity for c-erbB
      2 was observed in 21 %. According to the Lauren classification, a higher
      frequency of c-erbB-2 positive staining was observed in intestinal type tumors
      (70%). During the follow-up period 43% of the patients with c-erbB-2 oncoprotein
      negative tumors and 45% of the patients with c-erbB-2 oncoprotein-positive tumors
      died. There was no significant association between c-erbB-2 staining and sex,
      age, clinical stage, tumor grade, histological type or survival rates. In
      conclusion, almost half of the gastric cancers were positive for c-erbB-2.
      Nonetheless, the expression of c-erbB-2 oncoprotein did not play a role in
      prognosis.

PMID- 11820722
TI  - Estrogen and progesterone receptors in colorectal cancer and surrounding mucosa.
AB  - In this prospective study we have quantified by means of ELISA-methods the
      cytosolic content of estrogen (ER) and progesterone receptors (PgR) in tumoral
      tissue and paired normal mucosa from 163 patients with resectable colorectal
      cancer. Survival analysis was performed in a subgroup of 120 patients and the
      mean follow-up period was 24.9 months. The cutoff for ER and PgR levels was set
      at 1 fmol/mg protein. On the basis of this cutoff 20.9% of the cancers were ER
      positive and 25.8% were PgR positive; normal adjacent tissue presented ER in
      18.4% and PgR in 24.5%. Our results did not show any significant correlation
      between ER and PgR levels in neoplastic tissues. Howewer, a correlation was found
      in normal mucosa samples (p=0.02). Statistical analysis showed that there was no
      correlation between tumor ER and PgR content and patient age or sex, tumor
      location, Dukes' stage, histological differentiation, DNA ploidy status and S
      phase fraction. Furthermore, the results did not show any statistical differences
      in relapse-free and overall survival curves calculated for patients classified
      according to the hormone receptor content of their tumors. ER and PgR were
      detected at low levels in normal and neoplastic colorectal tissues without any
      significant relationship to either clinicopathological tumor characteristics or
      patient outcome. Their possible role in colorectal cancer remains to be
      elucidated.

PMID- 11820723
TI  - Evaluation of chromogranin A expression in serum and tissues of breast cancer
      patients.
AB  - Human chromogranin A (CgA) is a member of the granin family and is widely
      distributed in large dense core granules of endocrine and neuroendocrine cells. A
      variety of non-neuroendocrine carcinomas arising in various tissues show patterns
      of neuroendocrine differentiation. Expression of CgA has been documented in
      epithelial cells of normal mammary gland as well as in breast cancers, and
      elevation of serum CgA has been detected in patients with breast cancer. Our
      study was undertaken to evaluate the relationship between serum CgA levels and
      neuroendocrine features in breast cancer. In addition, we evaluated the
      expression of serum CgA in patients affected by breast cancer compared to
      controls and the relationship between serum CgA and tumor histology, extent of
      disease, lymph node status, tumor stage and serum CA 15.3 levels. We enrolled 266
      patients with infiltrating ductal or lobular breast carcinoma and a group of 100
      age-matched healthy women serving as controls. Serum CgA and CA 15.3 were assayed
      by specific immunoradiometric methods. The overall sensitivity of CgA and CA 15.3
      was 0.06 and 0.34, respectively (chi2 19.1, p<0.0005). No relationship was found
      between serum levels of CgA and tumor histology, extent of disease, lymph node
      status or tumor stage while serum levels of CA 15.3 were strongly correlated with
      all these variables but tumor histology. No relationship was found between serum
      levels of CgA and CA 15.3. Immunostaining against CgA, CgB, NSE and synaptophysin
      was performed on primary tumor tissue of 14 serum CgA-positive and 24 serum CgA
      negative patients and was negative in all cases. We also evaluated eight cases of
      pathologically-proven neuroendocrine breast cancer: only four and two of these
      showed positive CgA immunostaining and increased serum CgA concentration,
      respectively. In conclusion, serum CgA assay offers no additional information
      regarding the presence, the extent and the histology of breast cancer compared to
      the CA 15.3 assay. Moreover, serum CgA was not an accurate marker to identify or
      exclude the rare neuroendocrine differentiation of breast cancer. We therefore
      conclude that CgA is not useful as a serum marker in breast cancer.

PMID- 11820724
TI  - The efficacy of retroviral herpes simplex virus thymidine kinase gene transfer
      and ganciclovir treatment on the inhibition of melanoma growth in vitro and in
      vivo.
AB  - One approach to gene therapy of cancer is based on the insertion of a suicide
      gene into tumor cells and subsequent activation of the suicide mechanism. We used
      the herpes simplex virus thymidine kinase (HSVtk) gene followed by ganciclovir
      (GCV) treatment. The goal of our experiments was to determine the effectiveness
      of HSVtk gene therapy in malignant melanoma. B16BL6 murine melanoma cells
      retrovirally transduced with the HSVtk gene became sensitive to low
      concentrations of GCV. Analysis by RT-PCR showed HSVtk expression in transduced
      B16BL6tk+ cells. Apoptotic cell death was found in B16BL6tk+ cells treated with
      GCV (20 microM). The sensitivity of B16BL6tk+ cells to GCV was also examined in
      vivo. Tumors inoculated subcutaneously into C57BL6 mice regressed rapidly when
      treated with GCV (50 mg/kg twice a day) and disappeared completely after 14 days
      treatment. The mice remained in remission for 5 months. A bystander effect
      through which nontransduced B16BL6 cells were also inhibited by GCV
      administration when cocultured with B16BL6tk+ cells was expected. However, only
      slight killing of nontransduced cells was observed in vitro. Analysis of the
      bystander effect in vivo showed complete regression of tumors inoculated with a
      mixture of cells mostly consisting of B16BL6tk+ cells. A distant bystander effect
      was also examined. There was no regression of wild-type tumors raised at a
      distant site from primary B16BL6tk+ tumors. The failure of a more effective
      bystander effect indicates the need for further investigation of the possible use
      of combined gene therapy to treat melanoma.

PMID- 11820725
TI  - Effect of semipermeable membranes on skin barrier repair following tape
      stripping.
AB  - Reports in the literature suggest that the permeability of a wound dressing to
      water transport is an important variable in the healing of superficial wounds.
      Factors that influence skin hydration during barrier repair, therefore, are
      important in the optimization of wound treatments. In this study, the effects of
      semipermeable films on human skin following a standardized wound (tape stripping)
      were evaluated using measurements of transepidermal water loss (TEWL), skin
      hydration, rate of moisture accumulation, and erythema. Wounds treated with
      semipermeable films underwent more rapid barrier recovery than either unoccluded
      wounds or wounds under complete occlusion. Barrier films that produced
      intermediate levels of skin hydration during recovery produced the highest
      barrier repair rates. The results support the hypothesis; that semipermeable
      wound dressings augment barrier repair and skin quality by providing an optimized
      water vapor gradient during the wound healing process. The choice of wound
      dressing is discussed within the larger context of the design of vapor-permeable
      fabrics (smart materials) and the new fields of corneotherapy and comfort
      science.

PMID- 11820726
TI  - Broad specificity alkaline proteases efficiently reduce the visual scaling
      associated with soap-induced xerosis.
AB  - In xerotic skin, the proteolysis of desmosomes is reduced leading to the
      accumulation of corneocytes on the surface of the skin. The effect of proteases
      applied topically to soap-induced xerotic skin was evaluated using a five-point
      visual scale. The visual scaling associated with soap-induced xerosis could be
      ameliorated by the topical application of exogenous protease. Bovine pancreatic
      chymotrypsin, papain, and a bacterial protease from Bacillus licheniformis were
      all capable of facilitating the reduction in visual scaling in a short time.
      Alcalase and Optimase, both broad specificity alkaline bacterial proteases, were
      the most weight-efficient at delivering this clinical effect. The reduction in
      scaling could be achieved either by occluded application of an aqueous enzyme
      solution or by a two-step unoccluded application first of an aqueous enzyme
      solution followed by a commercial moisturizer. Morphological and immunological
      analysis of bacterial enzyme-treated skin revealed that topically applied
      protease specifically induced the degradation of the desmosomes thereby promoting
      desquamation. These results indicate that topical application of protease can
      significantly and rapidly reduce the visual scaling associated with soap-induced
      xerosis by promoting desmosome degradation within the corneocyte clumps.

PMID- 11820727
TI  - The IL-6 family cytokines, interleukin-6, interleukin-11, oncostatin M, and
      leukemia inhibitory factor, enhance mast cell growth through fibroblast-dependent
      pathway in mice.
AB  - Mast cell hyperplasia is observed in various inflammatory skin diseases. Although
      the mechanisms involved in the pathogenesis of these conditions remains largely
      uninvestigated, it is speculated that mediators produced in the lesional skin
      provide a favorable microenvironment for mast cell growth. Among the
      proinflammatory mediators, leukemia inhibitory factor (LIF), which shares a
      receptor component (gp130 subunit) with interleukin-6 (IL-6), has been identified
      as a mast cell growth-enhancing factor produced by cells of the keratinocyte
      derived cell line (KCMH-1). In this study, we investigated the effect of four IL
      6 family cytokines, IL-6, IL-11, oncostatin M (OSM) and LIF on mast cell growth
      in a mast cell/fibroblast co-culture system. When mouse bone marrow-derived
      cultured mast cells (BMMC) were maintained on a NIH/3T3 fibroblast monolayer,
      these cytokines induced proliferation of the mast cells, but none of the
      cytokines had any effect on mast cell proliferation in the absence of
      fibroblasts. mRNA for gp130 and receptors for the four IL-6 family cytokines were
      detected in NIH/3T3 fibroblasts by reverse transcriptase-mediated polymerase
      chain reaction. In contrast, only mRNA for the IL-11 receptor and gp130 were
      detected in BMMC. Tyrosine phosphorylation of gp130 was observed in NIH/3T3
      fibroblasts after stimulation with all the cytokines. Some IL-6 family cytokines
      enhanced the production of stem cell factor (SCF), a potent mast cell growth
      factor, from NIH/3T3 fibroblasts, but the amount of SCF produced by NIH/3T3
      fibroblasts was not paralleled by the mast cell growth-enhancement induced by the
      IL-6 family cytokines. When anti-SCF antibody was added with the IL-6 family
      cytokines in the BMMC/fibroblast coculture system, a significant effect of these
      cytokines remained, although the growth-enhancing activity was markedly reduced.
      A similar result was obtained when BMMC were prepared from W/W(V)-mice, which
      lack functional c-kit, in the BMMC/ fibroblast coculture system. These results
      suggest that IL-6 family cytokines stimulate mast cell growth by a fibroblast
      dependent mechanism, and also suggest the existence of another pathway between
      BMMC and NIH/3T3 fibroblasts cooperating with the SCF/c-kit pathway. IL-6 family
      cytokines may thus contribute to mast cell hyperplasia in skin diseases.

PMID- 11820729
TI  - Coenzyme A stimulates collagen production in cultured fibroblasts; possible
      mechanisms in enzymatic and gene expression.
AB  - Coenzyme A, a cofactor in enzymatic acetyl transfer reactions, stimulates
      collagen production in cultured fibroblasts. The mechanisms involved in this
      collagen stimulation were investigated. Enzymatic studies using radiolabeled
      procollagen as substrate revealed that coenzyme A enhanced prolyl hydroxylase
      activity. Prolyl hydroxylase is a key enzyme in collagen synthesis acting by
      hydroxylation of proline residues in procollagen peptide, which is necessary for
      stabilizing collagen. Northern blot analysis demonstrated that coenzyme A also
      enhanced mRNA levels of both the alpha subunit of prolyl hydroxylase and the
      alpha1 chain of type I collagen. The levels of protein production of prolyl
      hydroxylase and type I collagen were also increased in cultured fibroblasts by
      coenzyme A, which correlated well with observations from Northern blotting. On
      the other hand, coenzyme A did not stimulate the activity nor the gene expression
      of two other processing enzymes: lysyl hydroxylase, which provides the sites for
      glycosylation and crosslinking between collagen peptides, and lysyl oxidase, a
      fundamental enzyme in intermolecular crosslinking. These results indicate that
      coenzyme A stimulates collagen production by at least two separate mechanisms: by
      enhancing prolyl hydroxylase activity as well as stimulating gene expression of
      the alpha subunit of this enzyme, and by stimulating gene expression of alpha1
      chain of type I collagen.

PMID- 11820728
TI  - Pretreatment with topical all-trans-retinoic acid is beneficial for wound healing
      in genetically diabetic mice.
AB  - OBJECTIVE: Topical pretreatment with aIl-trans-retinoic acid (atRA) is known to
      improve healing of cutaneous wounds. We tested the effect of atRA on wound
      healing of genetically diabetic db/db mice. It is known that cutaneous wounds of
      db/db mice show delayed wound healing due to impaired wound contraction, delayed
      granulation tissue formation and underexpression of keratinocyte growth factor
      (KGF). METHODS: 0.1% atRA in 100 mg aqueous gel was applied to the back skin of
      db/db mice as well as to their normal heterozygous littermates, db/+ mice, for
      five consecutive days, and 2 days after completion of the atRA treatment, two
      round excisional wounds were created down the panniculus carnosus with a 6-mm
      punch biopsy on the back skin of each mouse. RESULTS: After 5 days treatment with
      0.1% atRA, significant hypertrophy of the epidermis and dermis,
      neovascularization, and inflammatory cell invasion were seen in the skin of the
      db/db mice, but these effects were seen only weakly in db/+ mice. Wounds in atRA
      treated db/db mice closed more rapidly than those in vehicle-treated db/db mice.
      KGF mRNA expression, which is usually significantly lower in db/db mice than in
      normal mice, in wounds of atRA-treated db/db mice on day 1 of treatment was as
      strong as in db/+ mice. CONCLUSION: Pretreatment with atRA reversed the impaired
      wound healing in db/db mice.

PMID- 11820731
TI  - Association of factor V Leiden and prothrombin gene mutation with Behcet's
      disease.

PMID- 11820730
TI  - Mast cell-independent increase of type I collagen expression in experimental
      scleroderma induced by bleomycin.

PMID- 11820732
TI  - Analysis of the p16 gene status of non-familial dysplastic nevus syndrome
      patients.

PMID- 11820733
TI  - On the conversion of solid cancer excess relative risk into lifetime attributable
      risk.
AB  - Risk coefficients representing the lifetime radiation-induced cancer mortality
      (or incidence) attributable to an exposure to ionizing radiation, have been
      published by major international scientific committees. The calculations involve
      observations in an exposed population and choices of a standard population (for
      risk transportation), of suitable numerical models, and of computational
      techniques. The present lack of a firm convention for these choices makes it
      difficult to inter-compare risk estimates presented by different scientific
      bodies. Some issues that relate to a necessary harmonization and standardization
      of risk estimates are explored here. Computational methods are discussed and, in
      line with the approach utilized by ICRP, conversion factors from excess relative
      risk (ERR) to lifetime attributable risk (LAR) are exemplified for exposures at
      all ages and for occupational exposures. A standard population is specified to
      illustrate the possibility of a simplified standard for risk transportation
      computations. It is suggested that a more realistic perception of lifetime risk
      could be gained by the use of coefficients scaled to the lifetime spontaneous
      cancer rates in the standard population. The resulting quantity lifetime
      fractional risk (LFR) is advantageous also because it depends much less on the
      choice of the reference population than the lifetime attributable risk (LAR).

PMID- 11820734
TI  - Childhood leukemia in Belarus before and after the Chernobyl accident: continued
      follow-up.
AB  - Earlier assessments led to the conclusion that due to the added radiation after
      the Chernobyl accident, childhood leukemia in Belarus was not recognisably
      increased in the years 1987-1994 compared to the years 1982-1986, i.e. the period
      before the accident. The present paper gives the data of the continued follow-up
      (1995-1998) which was conducted by the Institute of Haematology and Blood
      Transfusion, Minsk. In line with the earlier observations no increase has been
      identified. The incidence rates have been compared to the data of the newly
      established Belarussian Childhood Cancer Registry and a tentative explanation is
      given for apparent differences between the rates from our follow-up and the data
      reported earlier by the Belarussian Childhood Cancer Registry.

PMID- 11820735
TI  - A consistent two-mutation model of lung cancer for different data sets of radon
      exposed rats.
AB  - A two-mutation carcinogenesis model, formulated in terms of biologically
      motivated equations for mutation and expansion steps, has been applied in a
      mechanistic modelling of the lung cancer incidence in two large data sets of rats
      exposed to radon, both separately and jointly. Results indicate that (1) the
      equations employed are able to provide an accurate description of the separate
      data sets, (2) the parameters in the equations take on similar values for both
      data sets, and (3) it is possible to construct a consistent and well-fitting
      solution for the joint data set. It proved not to be necessary to take into
      account the effect of uranium ore dust, administered to part of the data or the
      different rat strains of the data sets. The joint solution provides a firm basis
      to investigate the effects of exposure, exposure rate and age at exposure on
      cumulative incidence, excess relative risk and excess absolute risk. For the same
      total exposure, cumulative incidence reaches a maximum for exposure rates between
      1 and 10 WLM per day. The so-called inverse-exposure-rate effect acts for higher
      exposure rates. The influence of age at exposure, however, seems to be even more
      pronounced. Exposure at a young age leads to considerably higher incidences than
      exposure at a later age. Parameters derived in this study compare fairly well
      with those derived for uranium miners, suggesting that a consistent model
      description for the induction of lung cancer by radon in rats and humans may be
      possible.

PMID- 11820736
TI  - Fetal dose assessment for the offspring of the Techa Riverside residents.
AB  - Massive releases of fission products from the plutonium facility Mayak (Southern
      Urals, Russia) resulted in the contamination of the Techa river and its
      floodlands (1949-1956). The results of long-term studies of exposure populations
      have been used for different purposes of retrospective dosimetry. The riverside
      residents were exposed via various pathways and their progeny were exposed in
      utero both to external radiation and to internal radiation from radionuclides
      ingested by the mothers prior to conception and during pregnancy. Fetal doses due
      to 90Sr from the maternal skeleton were estimated and compared with doses from
      other pathways. Individual red bone marrow (RBM) doses to the late fetuses were
      calculated on the basis of 90Sr contents measured in the maternal skeleton and
      the 90Sr transfer coefficients (TC) to the fetal skeleton were determined on the
      basis of the Techa river data. Two values of TC were assumed depending on the
      mothers' maturation status in the period of maximum releases: TC=0.2 for group 1
      (adulthood of mothers in 1950) and TC=0.02 for group 2 (mothers not yet in
      menarche age in 1950). Fetal doses in both groups that resulted from the
      different TC values varied by a factor of about 5-8. Furthermore, the fetal RBM
      doses due to 90Sr from the maternal skeleton were found to depend on the
      distances from the site of release and the time after major 90Sr intake. The
      average fetal RBM doses in the population of the upper, middle and lower Techa
      riverside regions were close to the ratio 3:2:1 and 20 years after the onset of
      contamination, the fetal doses have decreased by a factor of about 3-5. The
      distance from the site of release determined the relative contribution of
      different pathways to the fetal dose. For the settlements that are located
      closest to the site of release, the external exposure was of major concern up to
      the date of evacuation. For the non-evacuated settlements, the contribution of
      internal doses was higher and after 1956, external exposure is assumed to be
      negligible. From 1956 on, 90Sr that has been transferred from the maternal
      skeleton was practically the single source of in utero exposure.

PMID- 11820737
TI  - Long-term external radiation exposure of inhabitants in the western Bryansk
      region of Russia as a consequence of the Chernobyl accident.
AB  - The western Bryansk region in south-western Russia was highly contaminated with
      137Cs and 134Cs due to the Chernobyl accident in 1986. In 1990, a joint Nordic
      Russian project was initiated in order to make measurements and estimates of the
      absorbed doses to selected groups of inhabitants in this area. The participating
      individuals were living in small villages with contamination levels between 0.9
      and 2.7 MBq m(-2). Only some villages had been decontaminated. Both school
      children and adults participated in the study and the number of persons was
      between 100 and 130 each year, residing in 5 villages. Every year in September
      October, from 1990 to 1998. we performed individual measurements of external
      absorbed doses, assessed with thermoluminescent (TL) dosemeters (LiF). The mean
      effective dose per year from external irradiation due to the Chernobyl accident
      of the inhabitants in the villages ranged between 0.8 and 2.9 mSv during the
      study period and decreased with an apparent half-time of 3.7-8.2 years, depending
      on village and group. The highest individual doses within one village were, on
      average higher by a factor of 3 than the mean value for that village. Under the
      conservative assumption of a decrease rate in the external effective dose of 2%
      per year after 1998, individuals in the most highly exposed village are assumed
      to receive a life-time effective dose of about 75 mSv (between 1986 and 2056)
      from external exposure to caesium radionuclides. The mean value for the villages
      under study was estimated to be around 65 mSv using the assumed rate of decrease.

PMID- 11820738
TI  - Micronuclei and apoptosis in glioma and neuroblastoma cell lines and role of
      other lesions in the reconstruction of cellular radiosensitivity.
AB  - It is now well established that micronuclei frequency does not always rank cell
      lines according to radiosensitivity. There is, however, a growing interest in
      reconstructing cellular radiosensitivity (measured by colony assay) from
      concurrent micronucleus and apoptosis data. Using a variety of radiosensitive and
      radioresistant cell lines, we have derived a missing parameter--Poe, the
      probability of cell death by other events such as small deletions, chromosome
      aberrations, late apoptosis and necrosis which are undetectable by micronucleus
      and apoptosis assays performed at a single time point. In the radioresistant
      glioma cell lines G120, G60, G28, G44 and G62 (SF2 > or =0.59), a characteristic
      threshold dose exists above which cell loss due to undetectable lesions occurs.
      In the radiosensitive SK-N-SH and KELLY cell lines (SF2 < or =0.43), the Poe
      parameter is positive at very low doses, reaches a maximum and declines at higher
      doses. In the radiation resistant G28 cells, Poe was found to be below zero for
      doses up to 6 Gy. In the G62, G44 and G120 cell lines, the threshold doses to
      induce Poe events were 0.87, 3.04 and 3.85 Gy, respectively. Cell death by
      undetectable lesions is a cell-specific and time-dependent variable. Micronucleus
      and apoptosis assays performed concurrently and at a specific time point miss
      cell death due to other events and this may be the reason why reconstruction of
      cellular radiosensitivity from micronucleus and apoptosis data fails.

PMID- 11820739
TI  - Distinct apoptotic phenotypes induced by radiation and ceramide in both p53-wild
      type and p53-mutated lymphoblastoid cells.
AB  - The tumour suppressor gene p53 and the intracellular signalling molecule ceramide
      have both been shown to play crucial roles in the induction of apoptosis by
      ionising radiation. In this study we examined whether p53 and ceramide are
      involved in independent signal pathways, inducing different types of apoptosis.
      TK6 (p53wt/wt) and WTK1 (p53mut/mut) lymphoblastoid cells were treated with
      ionising radiation or N-acetyl-D-sphingosine (C2-ceramide). Flow cytometry and
      fluorescence microscopy studies were performed to characterise the time kinetics
      and morphological features of induced apoptosis. Ceramide- and radiation-induced
      apoptotic cells display characteristic differences in morphology and DNA staining
      and ceramide-induced apoptosis is expressed much faster than radiation-induced
      apoptosis. Radiation-induced apoptosis is p53-dependent and ceramide-induced
      apoptosis is p53-independent. The p53 pathway and the ceramide pathway are two
      independent signal pathways leading to distinct types of apoptosis. Since p53 is
      very often dysfunctional in tumour cells, modifying the ceramide pathway is a
      promising strategy to increase tumour sensitivity to radiation and other
      anticancer agents.

PMID- 11820740
TI  - TEL1 from Saccharomyces cerevisiae suppresses chromosome aberrations induced by
      ionizing radiation in ataxia-telangiectasia cells without affecting cell cycle
      checkpoints.
AB  - The TEL1 gene from Saccharomyces cerevisiae has been shown to be the closest
      sequence homologue to ATM, the gene mutated in ataxia-telangiectasia (A-T)
      patients. Functional homology shared between the ATM and Tell proteins has
      recently been demonstrated based on heterologous expression of the TEL1 gene in
      human cells derived from A-T patients. TEL1 expression complemented specific
      cellular A-T deficiencies, i.e. increased radiation-induced apoptosis, telomere
      shortening and spontaneous hyperrecombination. The mechanism of cellular A-T
      complementation by TEL1 appears to be independent of p53-dependent signaling
      cascades, since the deficiency of A-T cells to properly induce p53 upon ionizing
      radiation was not corrected by TEL1. We now find that the basic number of
      chromosome aberrations is increased and the number of radiation-induced
      chromosome aberrations is suppressed in A-T cells upon TEL1 expression. In cell
      cycle analyses, we find no changes in basic cell cycle distribution or in
      radiation-induced cell cycle checkpoints following TEL1 expression. We conclude
      that the radioprotective function of the Tel1 protein includes suppression of
      apoptosis and suppression of chromosome aberrations, and that both cellular end
      points can be uncoupled from ionizing radiation-induced cell cycle checkpoints.

PMID- 11820741
TI  - Correlated hit probability and cell transformation in an effect-specific track
      length model applied to in vitro alpha irradiation.
AB  - In estimating the risk from low doses of alpha particles such as those emitted by
      radon progeny, it is important to consider the correlation between cellular
      inactivation and transformation that can exist at the cellular level. A
      phenomenological model of radiation-induced cellular inactivation and
      transformation at this level is presented here which incorporates aspects of a
      state vector model of radiation carcinogenesis and of correlated hit
      probabilities for inactivation and transformation. The general form of the model
      assumes that both inactivation and initial initiation damage are produced through
      the interaction of sublesions induced by radiation passing through cell nuclei,
      with the production of sublesions governed by hit probabilities and a
      characteristic probability-per-unit track length. The inactivation and initiation
      events are partially correlated through the use of hit probabilities. In
      addition, promotional events are incorporated for the case of cellular
      transformation based on a previously published state vector model. The model
      provides good fits to available data on the relationship between inactivation,
      transformation and LET for doses of alpha above 0.1 Gy in the range of LETs
      commonly produced by radon and progeny; by "good fits" we mean here the ability
      to yield the correct shapes of dose-response data using parameter values that
      vary smoothly with LET and using inactivation parameters that are applied
      consistently between inactivation and transformation assays. The resulting model
      correctly predicts recent findings indicating an increased transformation
      frequency per surviving cell when a population receives a distribution of hits
      compared to irradiation where all cells receive the same number of hits.

PMID- 11820742
TI  - A metabolic derivation of tritium transfer coefficients in animal products.
AB  - Tritium is a potentially important environmental contaminant originating from the
      nuclear industry, and its behaviour in the environment is controlled by that of
      hydrogen. Animal food products represent a potentially important source of
      tritium in the human diet and a number of transfer coefficient values for tritium
      transfer to a limited number of animal products are available. In this paper we
      present an approach for the derivation of tritium transfer coefficients which is
      based on the metabolism of hydrogen in animals. The derived transfer coefficients
      separately account for transfer to and from free (i.e. water) and organically
      bound tritium. A novel aspect of the approach is that tritium transfer can be
      predicted for any animal product for which the required metabolic input
      parameters are available. The predicted transfer coefficients are compared to
      available independent data. Agreement is good (R2=0.97) with the exception of the
      transfer coefficient for transfer from tritiated water to organically bound
      tritium in ruminants. This may be attributable to the particular characteristics
      of ruminant digestion. We show that tritium transfer coefficients will vary in
      response to the metabolic status of an animal (e.g. stage of lactation, diet
      digestibility etc.) and that the use of a single transfer coefficient from diet
      to animal product is inappropriate. It is possible to derive concentration ratio
      values from the estimated transfer coefficients which relate the concentration of
      tritiated water and organically bound tritium in an animal product to their
      respective concentrations in the animals diet. These concentration ratios are
      shown to be less subject to metabolic variation and may be more useful
      radioecological parameters than transfer coefficients. For tritiated water the
      concentration ratio shows little variation between animal products ranging from
      0.59 to 0.82. In the case of organically bound tritium the concentration ratios
      vary between animal products from 0.15 (goat milk) to 0.67 (eggs).

PMID- 11820743
TI  - Effect of low-dose irradiation on induction of an apoptotic adaptive response in
      the murine system.
AB  - The aim of the study was to investigate the effect of low doses of irradiation on
      the induction of an apoptotic adaptive response in the murine system using
      C3H/HeJ mice bearing 8 mm syngeneic tumors, HCa-I and OCa-I. In OCa-I, the 0.05
      Gy priming dose significantly reduced the 25 Gy-induced apoptosis by 30%, whereas
      this reduction was not seen in HCa-I. The analysis of apoptosis-regulating
      molecules showed that the application of a priming dose increased the radiation
      induced p53 level in both tumors. No other regulators changed in OCa-I. However,
      in HCa-I, the application of a priming dose increased radiation-induced Bcl-XL
      and Bcl-XS, but not Bcl-2 or Bax. An apoptotic adaptive response induced by low
      dose radiation was shown in one murine tumor, OCa-I and Bcl-XL and Bcl-XS
      appeared to be implicated.

PMID- 11820745
TI  - The probability-outcome correspondence principle: a dispositional view of the
      interpretation of probability statements.
AB  - This article presents a framework for lay people's internal representations of
      probabilities, which supposedly reflect the strength of underlying dispositions,
      or propensities, associated with the predicted event. From this framework, we
      derive the probability-outcome correspondence principle, which asserts that
      strong dispositions should lead to (1) strong (forceful) and (2) immediate
      outcomes and, hence, be characterized by high probabilities. In contrast, weak
      dispositions lead to (1) weak (fragile) and (2) delayed outcomes and are thus
      associated with low probabilities. We describe six experiments designed to test
      the correspondence principle. In the final discussion, we examine the
      implications of the proposed framework, from both a normative and a descriptive
      viewpoint.

PMID- 11820744
TI  - An eye movement study of insight problem solving.
AB  - The representational change theory of insight claims that insight problems cause
      impasses because they mislead problem solvers into constructing inappropriate
      initial representations. Insight is attained when the initial representation is
      changed. In the present study (N = 24), we tested three specific implications of
      these hypotheses against eye movements recorded while participants solved
      matchstick arithmetic problems. The results were consistent with the predictions,
      providing converging evidence with prior findings using solution rates and
      solution times. Alternative theories of insight can explain individual findings,
      but only the representational change theory accounts for both the performance
      data and the eye movement data. The present study also suggests that eye movement
      recordings provide an important new window into processes of insight problem
      solving.

PMID- 11820746
TI  - Consistent contrast aids concept learning.
AB  - We suggest that coherence among concepts and correspondence between concepts and
      the world are important in concept learning. We identify one aspect of coherence,
      consistent contrast, and investigate its role in supervised concept learning.
      Concepts that contrast consistently carry information about the same attributes
      across the concepts within a contrast set. Concepts that contrast inconsistently
      predict and are predicted by values of different attributes. Experiment 1
      revealed a large advantage for consistent contrast in learning and
      generalization. Experiment 2 pitted similarity against consistency and still
      revealed an advantage of consistency. Experiment 2 also broadened the range of
      tasks considered to include inductions about novel categories and subjects'
      category descriptions. We discuss relations to theories of concept learning, to
      attentional mechanism, and to alignability, and we suggest practical
      implications.

PMID- 11820747
TI  - Impact of varying levels of expertise on decisions of category typicality.
AB  - Experts on domains of basic level object categories possess extensive knowledge
      of features used to both individuate and categorize groups of similar members.
      Two studies were conducted to determine the impact of high knowledge on
      intermediate and advanced experts' typicality decisions for basic and subordinate
      level category exemplars, and to investigate whether the pattern of influence of
      factors (in particular, central tendency and subjective familiarity) remained
      fixed throughout the continuum of expertise. Example goodness increased as a
      function of the level of specificity of the category for which typicality was
      rated. Subjective familiarity was the principal determinant of typicality for
      individuals with high knowledge, whereas central tendency was related to
      typicality when knowledge was not particularly high. Advanced and intermediate
      experts produced similar ratings of typicality, indicating that individuals'
      decisions of typicality do not change markedly once intermediate levels of
      competency have been attained. The incorporation of knowledge effects into models
      of semantic memory, as well as interactions among knowledge, psychological
      factors, and environmental factors in determining typicality, are discussed.

PMID- 11820748
TI  - The acquisition of automatic response biases through categorization.
AB  - Participants categorized left- and right-pointing line drawings presented
      together with pictures, whose pointing direction (to the left or right) was
      ambiguous (spatially ambiguous pictures; Experiments 1 and 2) or that pointed
      neither to the left nor to the right (spatially neutral pictures; Experiment 3).
      Subsequently, the spatially ambiguous and neutral pictures were used in a Simon
      task, wherein participants made left and right keypresses on the basis of the
      color of the pictures, while ignoring the object that they depicted. In all three
      experiments, performance was facilitated when the response required by the color
      matched the pointing direction of the line drawings with which the picture had
      been previously paired. Performance was impeded when the response required by the
      color did not match the pointing direction of the line drawings with which the
      picture had been previously paired. Thus, responses indirectly associated with
      pictures by category membership were automatically triggered even when the
      responses were inappropriate.

PMID- 11820749
TI  - The power law as an emergent property.
AB  - Recent work has shown that the power function, a ubiquitous characteristic of
      learning, memory, and sensation, can emerge from the arithmetic averaging of
      exponential curves. In the present study, the forgetting process was simulated
      via computer to determine whether power curves can result from the averaging of
      other types of component curves. Each of several simulations contained 100 memory
      traces that were made to decay at different rates. The resulting component curves
      were then arithmetically averaged to produce an aggregate curve for each
      simulation. The simulations varied with respect to the forms of the component
      curves: exponential, range-limited linear, range-limited logarithmic, or power.
      The goodness of the aggregate curve's fit to a power function relative to other
      functions increased as the amount of intercomponent slope variability increased,
      irrespective of component-curve type. Thus, the power law's ubiquity may reflect
      the pervasiveness of slope variability across component functions. Moreover,
      power-curve emergence may constitute a methodological artifact, an explanatory
      construct, or both, depending on the locus of the effect.

PMID- 11820750
TI  - Cognitive demands of face monitoring: evidence for visuospatial overload.
AB  - Young children perform difficult communication tasks better face to face than
      when they cannot see one another (e.g., Doherty-Sneddon & Kent, 1996). However,
      in recent studies, it was found that children aged 6 and 10 years, describing
      abstract shapes, showed evidence of face-to-face interference rather than
      facilitation. For some communication tasks, access to visual signals (such as
      facial expression and eye gaze) may hinder rather than help children's
      communication. In new research we have pursued this interference effect. Five
      studies are described with adults and 10- and 6-year-old participants. It was
      found that looking at a face interfered with children's abilities to listen to
      descriptions of abstract shapes. Children also performed visuospatial memory
      tasks worse when they looked at someone's face prior to responding than when they
      looked at a visuospatial pattern or at the floor. It was concluded that
      performance on certain tasks was hindered by monitoring another person's face. It
      is suggested that processing of visual communication signals shares certain
      processing resources with the processing of other visuospatial information.

PMID- 11820751
TI  - The effects of attention on perceptual implicit memory.
AB  - Reports on the effects of dividing attention at study on subsequent perceptual
      priming suggest that perceptual priming is generally unaffected by attentional
      manipulations as long as word identity is processed. We tested this hypothesis in
      three experiments by using the implicit word fragment completion and word stem
      completion tasks. Division of attention was instantiated with the Stroop task in
      order to ensure the processing of word identity even when the participant's
      attention was directed to a stimulus attribute other than the word itself. Under
      these conditions, we found that even though perceptual priming was significant,
      it was significantly reduced in magnitude. A stem cued recall test in Experiment
      2 confirmed a more deleterious effect of divided attention on explicit memory.
      Taken together, our findings delineate the relative contributions of perceptual
      analysis and attentional processes in mediating perceptual priming on two
      ubiquitously used tasks of word fragment completion and word stem completion.

PMID- 11820752
TI  - Stimulus-feature specific negative priming.
AB  - We report the results of two experiments that showed that the time needed to
      respond to a feature of a stimulus increases when that particular feature of that
      particular stimulus previously had to be ignored. The data of Experiment 2 argue
      against the hypothesis that the observed stimulus-feature specific negative
      priming was due to a response conflict instigated by automatic episodic retrieval
      of prime responses. Experiment 2 also showed that the effects were not caused by
      difficulties in switching between prime and probe tasks and provided additional
      evidence for the fact that priming effects were stimulus-feature specific. The
      present results suggest that the selective inhibition or episodic encoding
      mechanisms that are assumed to underlie negative priming can operate in a more
      specific and powerful manner than has been previously assumed.

PMID- 11820753
TI  - How events are reviewed matters: effects of varied focus on eyewitness
      suggestibility.
AB  - Witnesses to a crime or an accident perceive that event only once, but they are
      likely to think or talk about it multiple times. The way in which they review the
      event may affect their later memory. In particular, some types of review may
      increase suggestibility if the witness has been exposed to postevent misleading
      information. In Experiment 1, participants viewed a videotaped crime and then
      received false suggestions about the event. We found that participants who were
      then asked to focus on specific details when reviewing the event were more
      suggestible on a later source memory test than participants asked to review the
      main points. The findings of Experiment 2 suggest that this effect was not due to
      a criterion shift at test. These findings indicate that the type of rehearsal
      engaged in after witnessing an event can have important consequences for memory
      and, in particular, suggestibility.

PMID- 11820754
TI  - Episodic memory for object location versus episodic memory for object identity:
      do they rely on distinct encoding processes?
AB  - Three experiments were conducted to determine whether encoding processes that
      support episodic memory for object location are distinct from those that support
      memory for object identity. Guided by transfer-appropriate processing notions, we
      examined with an incidental learning paradigm whether an attentional focus on
      object location at encoding promotes subsequent recovery of object location,
      whereas a focus on object identity promotes recovery of object identity. We found
      that judging spatial relationships at encoding selectively supports recovery of
      object location, provided the test assesses memory for these relationships
      (rather than absolute location); our results also showed that judging physical
      and semantic object attributes promotes recovery of object identity
      preferentially. Contrasting with these domain-specific effects was evidence that
      identification processes involved in object naming boost memory for object
      identity as well as for absolute object location. Object identification at
      encoding may support memory performance in both domains by triggering the binding
      of identity and location information through a mechanism of object-based
      attentional selection.

PMID- 11820755
TI  - Negation and its impact on the accessibility of text information.
AB  - Prior experiments have shown that sentences such as (1) Mary bakes bread but no
      cookies lead to a reduced accessibility of the concept mentioned in the negated
      phrase, whereas sentences such as (2) Elizabeth burns the letters but not the
      photographs do not. In the present article, two explanations for this result are
      investigated. According to situation model theory (Johnson-Laird, 1983; van Dijk
      & Kintsch, 1983), the reason is that the entity mentioned within the negated
      phrase in (2) is not absent from the described situation. According to discourse
      representation theory (Kamp, 1981), in contrast, the negation operator in (2)
      does not reduce the accessibility of the negated concept, because the
      corresponding discourse referent is not introduced but merely referred to within
      the operator's scope. In two experiments, participants were presented with
      narrative texts including negation sentences that either introduced or referred
      to entities, and that either described a situation in which only the nonnegated
      or only the negated entity was present. The accessibility of the relevant
      concepts was measured by means of a probe recognition task. The results support
      the situation models explanation.

PMID- 11820756
TI  - Asymmetric activation of number codes in bilinguals: further evidence for the
      encoding complex model of number processing.
AB  - In two experiments, Filipino-English bilinguals were asked to verify simple
      addition equations that were presented either in digit, verbal-Filipino, or
      verbal-English formats and that included different types of sum probes. The main
      results show (1) faster and more accurate processing of digit and English items
      than of Filipino items, (2) stronger associative interference by type of probe
      with the digit and English items compared with the Filipino items, and (3)
      priming of responses from English to digit codes, and from Filipino to digit
      codes, but not vice versa. The results were explained by using an elaborated
      version of Campbell's (1994) encoding complex model with additional assumptions
      to address the experience of bilinguals. The additional assumptions relate to the
      preference among the bilingual's two verbal formats, the different strengths of
      activation pathways within each format, and the asymmetric activation across
      formats.

PMID- 11820757
TI  - Word frequency and memory: effects on absolute versus relative order memory and
      on item memory versus order memory.
AB  - Word frequency can produce opposite effects on recognition and order memory: Low
      frequency words produce greater recognition accuracy, whereas high-frequency
      words produce superior order memory. The present experiments further delineate
      the relationship between word frequency and order memory. Experiment 1 indicates
      that low-frequency words produce worse performance on a measure of absolute order
      memory but not on a test of relative order, which is consistent with the idea
      that different forms of information underlie different types of order judgments
      (Greene, Thapar, & Westerman, 1998). Experiment 2 contrasted high-, low-, and
      very low-frequency words on recognition memory and absolute order memory. In
      comparison with high-frequency words, low-frequency words enhanced recognition,
      whereas very low-frequency words did not. Both low- and very low-frequency words,
      however, produced worse memory for absolute order. Thus, the relationship between
      frequency and item memory is an inverted U-shaped function, whereas the
      relationship between frequency and absolute order memory is direct. This implies
      that the item-enhancing effects of lower word frequency may be dissociated from
      its order-disrupting effects.

PMID- 11820758
TI  - Word reading and picture naming in Italian.
AB  - Results from two separate norming studies of lexical access in Italian were
      merged, permitting a comparison of word-reading and picture-naming latencies and
      the factors that predict each one for an overlapping subsample of 128 common
      nouns. Factor analysis of shared lexical predictors yielded four latent
      variables: a frequency factor, a semantic factor, a length factor, and a final
      factor dominated by frication on the initial phoneme. Age of acquisition (AoA)
      loaded highly on the first two factors, suggesting that it can be split into
      separate sources of variance. Regression analyses using factor scores as
      predictors showed that word reading and picture naming are both influenced by the
      frequency/AoA factor. The semantics/AoA factor influenced only picture naming,
      whereas the length and frication factors influenced only word reading.
      Generalizability of these results to other languages is discussed, including
      potential effects of cross-language differences in orthographic transparency.

PMID- 11820759
TI  - Natural phenolic compounds 1900-2000: a bird's eye view of a century's chemistry.

PMID- 11820760
TI  - The development of strategies for terpenoid structure determination.

PMID- 11820761
TI  - Biocatalysis and enzymes in organic synthesis.

PMID- 11820762
TI  - Tannins: classification and definition.

PMID- 11820763
TI  - Natural sesquiterpenoids.

PMID- 11820765
TI  - Stigma and rejection: living with AIDS in villages in southern Thailand.
AB  - The problems that face HIV/AIDS patients are now fairly well documented. These
      include experiences of guilt, anger, grief, fear of abandonment, and potential
      economic hardship and marginalization due to others' fear of infection and
      associated stigma. However, limited attention has been paid to the effects of
      AIDS-related stigma on access to, and the provision of, health services.
      Understanding how the stigma of AIDS affects the processes and experiences of
      diagnosis, treatment, prevention, and care is critical to effective public health
      policy and the delivery of health care programs and medical services. In this
      article, we examine stigma as experienced by people with HIV and AIDS, and by
      their families, in village Thailand. We also identify areas for improvement
      pertaining to people with HIV/AIDS and other stigmatizing diseases.

PMID- 11820764
TI  - Plant natural products with leishmanicidal activity.

PMID- 11820766
TI  - A reconsideration of the origins of the type 2 diabetes epidemic among Native
      Americans and the implications for intervention policy.
AB  - Type 2 diabetes has reached epidemic proportions in many Native American
      communities in North America. The overwhelming majority of physicians, biomedical
      researchers, and medical ecologists continue to explain the astoundingly high
      prevalence rates of diabetes among Native Americans and other high prevalence
      populations in terms of yet-to-be-identified genetic factors. Recent experimental
      and epidemiological research, however, has brought to light an etiological
      alternative to the genetic-predisposition model. This body of research suggests
      that type 2 diabetes may result initially from fetal malnutrition and, in
      subsequent generations, be propagated via perturbations in the intrauterine
      environment. Native American populations at greatest risk for diabetes today are
      the ones most likely to have endured severe nutritional stress in their recent
      histories, thus experiencing the conditions that are most conducive to the
      diabetic developmental sequence. If further substantiated, the implications of
      the fetal-origin model of diabetes for diabetes intervention programs are
      profound.

PMID- 11820767
TI  - Healthy imaginations: a social history of the epidemiology of Aboriginal and
      Torres Strait Islander health.
AB  - It is difficult to imagine Aboriginal and Torres Strait Islander health without
      the powerful descriptors of epidemiology. The statistical imagery of numerical
      tables, pie charts, and bar graphs have become a key element in the public
      presentation of Indigenous public health issues. Such quantitative measurements
      of health draw on the authority of neutral, objective science and are thus rarely
      questioned in terms of their social meaning. This paper traces the history of
      this imagery through the 20th century, providing a social account of
      epidemiological description. Historical notions such as social Darwinism,
      assimilation, and dangerous other are all seen to be woven into the
      epidemiological text. The enormous rise in the epidemiological description of
      Indigenous health problems in recent years needs to be analyzed as a social
      phenomenon and, in particular, as an aspect of emerging forms of governmentality.
      Finally, it is argued that such analyses are needed in order to promote an
      anthropology of epidemiology and to avoid limiting medical anthropology to
      applications within epidemiology.

PMID- 11820768
TI  - Various perspectives on the origins of pathogens: questions of evidence.

PMID- 11820769
TI  - Pre-Columbian hookworm evidence from Tennessee: a response to Fuller (1997).

PMID- 11820770
TI  - American hookworm antiquity.

PMID- 11820771
TI  - Modulation of THP-1 macrophage and cholesterol-loaded foam cell apolipoprotein E
      levels by glycosphingolipids.
AB  - Macrophages synthesize and secrete apolipoprotein E (apoE) constitutively. This
      process is upregulated under conditions of cholesterol loading. The response to
      cholesterol is antiatherogenic as it is believed to promote cholesterol efflux
      from the artery wall. The concentration of lactosyl ceramide (LacCer), a
      glycosphingolipid recently discovered to regulate cellular signaling,
      proliferation, and expression of adhesion molecules, is also increased in
      atherosclerotic tissues. Here we have investigated the effect of exogenous LacCer
      on macrophage apoE levels. We show that increasing macrophage LacCer levels
      sevenfold led to reductions in cellular and secreted apoE (15 and 30%,
      respectively, over a 24-h period) as determined by enzyme-linked immunosorbent
      assay. A similar effect was also induced by glucosyl ceramide (GlcCer) but not by
      ganglioside species. When macrophages were converted to cholesterol-loaded foam
      cells by incubation with acetylated LDL, the resulting increase in cellular apoE
      levels was inhibited by 26% when the cells were subsequently enriched with
      LacCer. After metabolic labeling of cellular glycosphingolipids with
      [14C]palmitate, we also discovered that high-density lipoprotein (HDL) stimulates
      the efflux of glycosphingolipids from foam cells. These data imply that LacCer
      and GlcCer may be proatherogenic due to the suppression of macrophage apoE
      production. Furthermore, the efflux of glycosphingolipids from macrophage foam
      cells to HDL could indicate a potential pathway for their removal from the artery
      wall and subsequent delivery to the liver.

PMID- 11820772
TI  - Calmodulin and cyclin D anchoring sites on the Src-suppressed C kinase substrate,
      SSeCKS.
AB  - SSeCKS and its human orthologue, Gravin, are large scaffolding proteins that are
      thought to facilitate mitogenic control by anchoring key signal mediators such as
      protein kinase (PK) C, PKA, the plasma membrane associated isoform of alpha-1,4
      galactosyltransferase (GalTase), beta2-adrenergic receptor, and cyclins. SSeCKS
      is also a major PKC substrate and phosphatidylserine-dependent PKC binding
      protein whose phosphorylation sites shares homology with a site in the MARCKS
      protein that encodes phosphorylation-sensitive calmodulin (CaM) binding activity.
      In the present study, we mapped the in vitro binding sites for CaM and cyclins on
      SSeCKS. Four CaM binding sites were identified by binding assays that conform to
      the so-called 1-5-10 motif. Notably, CaM binding was antagonized by
      prephosphorylation of SSeCKS by PKC. We also identified two major cyclin binding
      (CY) sites that overlap a major PKC phosphorylation site in SSeCKS
      (Ser(507/515)), and showed that cyclin D binding is attenuated if SSeCKS is
      prephosphorylated by PKC. These data suggest that the scaffolding activities of
      SSeCKS are modulated by mitogenically stimulated kinases such as PKC.

PMID- 11820774
TI  - Hemoglobin equilibrium analysis by the multiangle laser light-scattering method.
AB  - Dimer-tetramer and monomer-dimer-tetramer equilibria of tetrameric hemoglobins
      and their single chains in the CO form, respectively, were evaluated using the
      microbatch multiangle light-scattering (MALS) analysis system. The molecular
      weights of human Hb A and Hb F in the CO form were dependent on concentration.
      The dissociation constants to dimers of Hb A and Hb F were 2.58 x 10(-6) and 0.66
      x 10(-6), respectively. Equilibration of single globin chains, including alpha,
      beta, and gamma chains, was also evaluated by the same method. The dissociation
      constants of alpha-chain dimers to monomers, of beta-chain tetramers to monomers,
      and of gamma-chain tetramers to dimers were 14 x 10(-6), 25 x 10(-17), and 6.86 x
      10(-6) M, respectively. These results indicate that the MALS analysis system can
      not only determine molecular weight but also characterize protein-protein
      interactions of multi-subunit proteins.

PMID- 11820773
TI  - Macrophage cholesterol efflux to free apoprotein A-I in C3H and C57BL/6 mice.
AB  - Cholesterol efflux from peritoneal macrophages of mice C57BL/6 susceptible and
      C3H resistant to atherosclerosis was compared, using apoprotein A-I as acceptor.
      The elicited macrophages were labeled with 3H-cholesterol and cholesterol
      enriched by incubation for 24 h with acetylated LDL. After incubation for 6 or 24
      h, 3H-cholesterol efflux to free apoA-I (10 microg/ml) was significantly higher
      with macrophages derived from C3H mice compared to C57BL/6 mice. The cells were
      also pretreated with 0.3-0.45 mM cyclic AMP, 10 microM 9-cis-retinoic acid or 10
      microM 22(R)-hydroxycholesterol, RXR and LXR ligands. Treatment with cyclic AMP,
      RXR, or LXR ligands, resulted in enhancement of 3H-cholesterol efflux in both
      strains. Under all conditions, 3H-cholesterol efflux was significantly higher in
      C3H compared to C57BL/6 macrophages. In conclusion, the higher cholesterol efflux
      from C3H macrophages could contribute toward the resistance of this strain to
      diet-induced atherosclerosis despite hypercholesterolemia.

PMID- 11820775
TI  - Copper inhibits activated protein C: protective effect of human albumin and an
      analogue of its high-affinity copper-binding site, d-DAHK.
AB  - Activated protein C (APC) is useful in the treatment of sepsis. Ischemia and
      acidosis, which often accompany sepsis, cause the release of copper from loosely
      bound sites. We investigated (i) whether physiological concentrations of copper
      inhibit APC anticoagulant activity and (ii) if any copper-induced APC inhibition
      is reversible by human serum albumin (HSA) or a high-affinity copper-binding
      analogue of the human albumin N-terminus, d-Asp-d-Ala-d-His-d-Lys (d-DAHK). APC
      activity after 30 min of incubation with CuCl2 (10 microM) was decreased 26%
      below baseline. HSA, both alone and when combined with various ratios of CuCl2,
      increased APC activity significantly above baseline. d-DAHK alone and 2:1 and 4:1
      ratios of d-DAHK:CuCl2 also increased APC activity. APC contained 1.4 microM
      copper, which helps explain the increased APC activity with HSA and d-DAHK alone.
      These in vitro results indicate that copper inhibits APC activity and that
      albumin and d-DAHK reverse the copper-induced APC deactivation.

PMID- 11820776
TI  - Structural changes of the erythrocyte as a marker of non-insulin-dependent
      diabetes: protective effects of N-acetylcysteine.
AB  - Prooxidant-antioxidant imbalance was considered as a hallmark of age-associated,
      non-insulin-dependent diabetes (NIDD). The aim of this ex vivo study was to
      investigate possible implications of oxidative stress in the integrity and
      function of red blood cells (RBCs) from NIDD patients. Morphometric and
      analytical cytology studies were conducted. The results showed: (i) significant
      alterations of RBC ultrastructure; (ii) relevant changes of spectrin
      cytoskeleton; (iii) altered insulin receptor distribution; and (iv) that
      treatment with the antioxidizing drug N-acetylcysteine was capable of
      significantly counteracting these changes. These results suggest a
      reconsideration of RBC integrity as a possible progression marker in NIDD.

PMID- 11820777
TI  - Isolation and characterization of a novel F-box protein Pof10 in fission yeast.
AB  - The SCF complex is a type of ubiquitin-protein ligase (E3) that consists of
      invariable components, including Skp1, Cdc53/Cul1, and Rbx1, as well as variable
      components known as F-box proteins. Using a yeast two-hybrid system, we isolated
      six proteins that interact with Schizosaccharomyces pombe Skp1. Among them, Pof10
      is a novel F-box protein consisting of 662 amino acids, harboring the F-box
      domain required for the binding to Skp1 and followed by four WD40 repeats.
      Overexpression of Pof10 in fission yeast resulted in loss of viability with
      marked morphological changes that are similar to those in pop1 mutant yeast.
      Coexpression of Skp1 with Pof10 prevented the lethality, suggesting that the
      lethality from Pof10 overexpression results from the sequestration of Skp1 from
      other F-box proteins including Pop1. Whereas most F-box proteins show rapid
      turnover, Pof10 has a remarkably long half-life in vivo and has been shown to be
      localized predominantly in cytoplasm. These results suggest that the stable F-box
      protein Pof10 might target abundant cytoplasmic proteins for degradation in
      fission yeast.

PMID- 11820778
TI  - Gamma-secretase-like cleavages of Notch and beta APP are mutually exclusive in
      human cells.
AB  - Presenilins 1 and 2 are two transmembrane proteins that seem necessary for
      controlling the proteolytic cleavages of two substrates, betaAPP and Notch,
      giving rise to Abeta (amyloid beta-peptide) and NICD (Notch Intracellular
      Domain), respectively. It is a matter for discussion whether presenilins act
      directly as the cleaving enzyme (referred to as gamma-secretase) or indirectly as
      a regulator of the substrates/enzymes trafficking to the permissive cell
      compartment where gamma-secretase cleavage could occur. Here we examined whether
      betaAPP and Notch undergo mutually exclusive proteolytic events in HEK293 cells
      or whether they behave as substrates able to compete for a single protease. We
      show that the overexpression of mDeltaE-Notch-1 does not influence the endogenous
      recovery of secreted and intracellular Abeta nor those derived from betaAPP
      overexpressing HEK293 cells. We establish, conversely, that increasing amounts of
      betaAPP do not modify the steady-state generation of NICD nor affect the kinetic
      of production. These data indicate that the proteolytic cleavages leading to the
      productions of Abeta and NICD are mutually exclusive events in HEK293 cells, and
      suggest that distinct proteolytic activities contribute to betaAPP and Notch
      processing.

PMID- 11820780
TI  - Characterization of the cellular and metabolic effects of a novel enzyme
      resistant antagonist of glucose-dependent insulinotropic polypeptide.
AB  - A novel N-terminally substituted Pro(3) analogue of glucose-dependent
      insulinotropic polypeptide (GIP) was synthesized and tested for plasma stability
      and biological activity both in vitro and in vivo. Native GIP was rapidly
      degraded by human plasma with only 39 +/- 6% remaining intact after 8 h, whereas
      (Pro(3))GIP was completely stable even after 24 h. In CHL cells expressing the
      human GIP receptor, (Pro(3))GIP antagonized the cyclic adenosine monophosphate
      (cAMP) stimulatory ability of 10(-7) M native GIP, with an IC(50) value of 2.6
      microM. In the clonal pancreatic beta cell line BRIN-BD11, (Pro(3))GIP over the
      concentration range 10(-13) to 10(-8) M dose dependently inhibited GIP-stimulated
      (10(-7) M) insulin release (1.2- to 1.7-fold; P < 0.05 to P < 0.001). In obese
      diabetic (ob/ob) mice, intraperitoneal administration of (Pro(3))GIP (25 nmol/kg
      body wt) countered the ability of native GIP to stimulate plasma insulin (2.4
      fold decrease; P < 0.001) and lower the glycemic excursion (1.5-fold decrease; P
      < 0.001) induced by a glucose load (18 mmol/kg body wt). Collectively these data
      demonstrate that (Pro(3))GIP is a novel and potent enzyme-resistant GIP receptor
      antagonist capable of blocking the ability of native GIP to increase cAMP,
      stimulate insulin secretion, and improve glucose homeostasis in a commonly
      employed animal model of type 2 diabetes.

PMID- 11820779
TI  - Full-length cDNA cloning of human neuroglobin and tissue expression of rat
      neuroglobin.
AB  - Neuroglobin is a recently discovered respiratory, porphyrin-containing protein
      that is expressed in the brain of mouse and human. However, the full-length cDNA
      sequence and genomic organization of human neuroglobin have not been reported. In
      this paper, the full-length cDNA sequence of human neuroglobin was cloned
      following bioinformatic analysis and the rapid amplification of cDNA ends (RACE)
      technique. It was shown that the full-length cDNA sequence (GenBank Accession No.
      AF422796) of human neuroglobin is 1909 bp in size, and the genomic sequence is
      8041 bp in size (GenBank Accession No. AF422797). To further study the
      characterization of this gene, the coding region of rat neuroglobin (GenBank
      Accession No. AF333245) was cloned by using degeneracy PCR. The result showed
      high conservation among human, rat, and mouse neuroglobin. Furthermore, it was
      demonstrated that NGB was extensively expressed in rat brain by using in situ
      hybridization and the immunohistochemical technique. Transcription of NGB mRNA
      was shown to be widely distributed throughout the adult rat brain, including
      cerebral cortex, hippocampus, thalamus, hypothalamus, olfactory bulb, and
      cerebellum. NGB protein immunoreactive cells were also widely distributed
      throughout normal adult rat brain, including cerebral cortex, hippocampus,
      thalamus, hypothalamus, pons, and cerebellum. It could be seen that the NGB
      immunopositive signals were in the cytoplasma and processes of the neuron. These
      data strongly support the notion that neuroglobin is a highly conserved gene in
      evolution and is very important in the nervous system, possibly related to the
      oxygen supply of the neuron.

PMID- 11820781
TI  - Induction of multidrug resistance proteins MRP1 and MRP3 and gamma
      glutamylcysteine synthetase gene expression by nonsteroidal anti-inflammatory
      drugs in human colon cancer cells.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) have been demonstrated to suppress
      colorectal tumorigenesis. NSAIDs have also been used to treat inflammatory
      illnesses. However, the underlying mechanisms of action by NSAIDs have not been
      completely elucidated. In this study, we reported that among the six members of
      the multidrug resistance protein gene (MRP1 to MRP6) family which encode membrane
      transporters for a diverse group of antitumor agents, expression of MRP1 and MRP3
      but not the others in human colorectal cancer cell lines was induced by sulindac.
      This induction profile is consistent with the results using prooxidants which
      produce reactive oxygen species (ROS) and generate oxidative stress as previously
      reported. Moreover, treatment of colorectal cancer cells with sulindac induced
      ROS. Suppression of ROS formation by antioxidant N-acetylcysteine (NAC)
      downregulated the induction of MRP1 and MRP3 expression. Expression of another
      oxidative stress-sensitive gene, gamma-glutamylcysteine synthetase heavy subunit
      gene (gamma-GCSh), which encodes the rate-limiting enzyme in glutathione
      biosynthesis, was also induced by sulindac. However, the suppression of sulindac
      induced gamma-GCSh expression by NAC was less sensitive compared with that of
      MRP1 and MRP3. We also demonstrated that induction of MRP3 and gamma-GCSh was
      independent of intracellular COX-2 levels. These results, collectively, suggest a
      ROS-related, COX-2-independent mechanism for the induction of drug resistance
      gene expression that bears important implications to the roles of NSAIDs in
      colorectal carcinogenesis and inflammatory response.

PMID- 11820782
TI  - ATP binding and hydrolysis and autophosphorylation of CbbQ encoded by the gene
      located downstream of RubisCO genes.
AB  - CbbQ is encoded by the gene located downstream of ribulose 1,5-bisphosphate
      carboxylase/oxygenase genes (cbbLS) in the thermophilic hydrogen-oxidizing
      bacterium, Hydrogenophilus thermoluteolus. The protein possesses two nucleotide
      binding motifs in its amino acid sequence, and it posttranslationally activates
      RubisCO. We present ATP hydrolysis and binding of CbbQ. CbbQ releases P(i) from
      ATP only in the presence of Mg(2+). CbbQ interacts with an 2'(3')-O-(2,4,6
      trinitrophenyl)adenosine 5'-triphosphate in the presence or absence of Mg(2+).
      The interaction with Mg(2+) and/or a nucleotide induces a conformational change
      in CbbQ. Autophosphorylation of CbbQ occurs only in the absence of Mg(2+).

PMID- 11820783
TI  - Stabilization of molten globule state of papain by urea.
AB  - Papain exists in molten globule (MG) state at pH 2.0 and in this state protein
      tends to aggregate in the presence of lower concentrations of guanidine
      hydrochloride (GuHC1). Such aggregation is prevented if a low concentration of
      urea is also present in the buffer; in addition, stabilization of the protein is
      also induced. Intrinsic fluorescence properties of papain as well as ANS binding
      suggest significant changes in the structure of papain, in the presence of urea
      with the absence of major changes in the secondary structure of the protein. The
      GuHCl- and temperature-induced unfolding of papain, in the presence of urea,
      indicates stabilization of the protein as seen from the higher transition
      midpoints, when monitored by fluorescence and circular dichroism (CD). However, a
      similar phenomenon is not seen under neutral conditions in the presence of urea
      either at low or high concentrations. The utility of prevention of aggregation by
      urea is also discussed.

PMID- 11820784
TI  - Src family kinase-dependent phosphorylation of a 29-kDa caveolin-associated
      protein.
AB  - PDGF receptors and Src family kinases are concentrated in caveolae, where signal
      transduction cascades involving these molecules are thought to be organized. The
      Src family tyrosine kinases are cotransducers of signals emanating from the
      activated PDGF receptor. However, the Src family kinase substrates that are
      involved in PDGF-induced signaling remain to be fully elucidated. We have
      identified a 29-kDa protein in caveolae that was phosphorylated in response to
      PDGF stimulation. This protein, pp29, was tightly bound to the caveolar coat
      protein caveolin-1. pp29 was among the most prominent phosphoproteins observed in
      cells overexpressing Fyn, suggesting that it may be a Fyn substrate. Consistent
      with this, pp29 was among a specific subset of proteins whose PDGF-stimulated
      phosphorylation was blocked by expression of kinase inactive Fyn. These data
      indicate that pp29 lies downstream of Fyn activation in a PDGF-stimulated
      signaling pathway, and that pp29 is an abundant site for nucleation of signal
      transduction cascades.

PMID- 11820785
TI  - Blocking HSF1 by dominant-negative mutant to sensitize tumor cells to
      hyperthermia.
AB  - Heat shock protein 70 (HSP70), an antiapoptotic chaperon protein, is highly
      expressed in human breast tumors and renders them resistant to such therapy as
      hyperthermia. In the present study, we inhibited the expression of HSP70 by
      blocking the heat shock transcription factor 1 (HSF1) function with its dominant
      negative mutant (mHSF1) in Bcap37 cells, a thermotolerant breast cancer cell
      line. Here we report that retrovirus-mediated transfer of mHSF1 led to massive
      cell death of Bcap37 after hyperthermia. mHSF1 sensitized Bcap37 cells to
      hyperthermia by promoting apoptosis induced by heat shock. We also examined the
      efficacy of mHSF1 gene therapy in the nude mouse. mHSF1 transfection led to
      diminution of tumor growth with hyperthermia therapy. Thus, disrupting HSF1 in
      combination with hyperthermia may open new possibilities for treatment of cancers
      that have acquired resistance to heat treatment.

PMID- 11820786
TI  - Arginine residues in domain V have a central role for bacteria-binding activity
      of macrophage scavenger receptor MARCO.
AB  - MARCO is a bacteria-binding macrophage-specific scavenger receptor that plays a
      role in innate immune response. MARCO has short intracellular and transmembrane
      domains, as well as a large extracellular domain composed of a spacer domain, a
      long collagenous domain, and a C-terminal scavenger receptor cysteine-rich domain
      (SRCR), domain V. As yet, no specific function has been assigned to the SRCR
      domain of scavenger receptors. In the present study, we generated several human
      and mouse MARCO variants with deletions or single amino acid substitutions and
      localized the primary bacteria-binding region to domain V. Furthermore, analysis
      of the MARCO variants containing only portions of domain V demonstrated a crucial
      role for an arginine-rich segment for this function. More precisely, the motif
      RXR was identified as an essential element for high-affinity bacterial binding.
      The results indicate that the binding properties of MARCO differ from those of
      the other class A scavenger receptors, SR-A and SRCL, whose ligand-binding
      function has been localized to the collagenous domain.

PMID- 11820787
TI  - Human endothelial Pyk2 is expressed in two isoforms and associates with paxillin
      and p130Cas.
AB  - Proline-rich kinase 2 (Pyk2) is a non-receptor tyrosine kinase belonging to the
      focal adhesion kinase family. Many stimuli can initiate phosphorylation and
      activation of Pyk2 but its specific activators and downstream targets are still
      largely unidentified and little is known of the mechanisms or role of Pyk2
      activation in endothelial cells. In human umbilical vein endothelial cells
      (HUVEC), we show that (1) Pyk2 is phosphorylated on tyrosine residues 402, 580,
      and 881 in response to stimulation with G-protein-coupled receptor agonists
      (GPCAs), vascular endothelial growth factor, and the cytokine interleukin-1alpha;
      (2) HUVEC express mRNA for two isoforms of Pyk2 which do not appear to be
      regulated transcriptionally by GPCAs, growth factors, or cytokines; and (3) Pyk2
      is localised to the cytosol and associates through its C-terminus with the
      cytoskeletal protein paxillin and the adapter molecule p130Cas in phosphorylation
      independent interactions. These results demonstrate that Pyk2 is rapidly
      activated and associates with structural and adapter proteins suggesting that it
      is an important kinase involved in mediating acute responses in endothelium.

PMID- 11820789
TI  - Induction of uPA but not NF-IL3A by calcitonin is dependent on Erk1/2
      phosphorylation in porcine renal cell line LLC-PK1.
AB  - Calcitonin (CT) is a polypeptide hormone and has a variety of functions including
      regulation of urinary calcium excretion. By using a cDNA subtraction
      hybridization method, we identified that NF-IL3A and urokinase-type plasminogen
      activator (uPA) genes were up-regulated by CT in porcine renal cell line LLC-PK1.
      CT-mediated induction of these genes was not inhibited by cycloheximide. These
      data suggest that these up-regulations are not induced by increased synthesis of
      regulating proteins; therefore, they are immediately response early (IE). We also
      found that CT treatment led to the phosphorylation of Erk1/2. We demonstrated
      that PD98059, a MEK1 inhibitor, inhibited CT-induced mRNA expressions of uPA, but
      had no obvious influence on the NF-IL3A induction. These results demonstrated the
      inductions of uPA by CT involve Erk1/2 phosphorylation. We provide the first
      evidence that NF-IL3A expression is up-regulated by CT. The present findings
      suggest that the transcriptions of the NF-IL3A and uPA could be induced by CT and
      might be important mediators of CT function in renal cells.

PMID- 11820788
TI  - Mast cell chymase regulates dermal mast cell number in mice.
AB  - Chymase inhibitor reduced the increase in the number of dermal mast cells in 2,4
      dinitrofluorobenzene-induced dermatitis in a dose-dependent manner. Intradermal
      injection of human chymase to mouse ear significantly increased histamine
      content, the marker for mast cell number in the skin. These results suggest that
      chymase released by mast cells may participate in local mast cell accumulation in
      a positive feedback fashion. Immunohistochemical analysis revealed that the
      intradermal injection of chymase reduces expression of stem cell factor (SCF) on
      surface of the skin keratinocytes. In addition, incubation of human keratinocytes
      with chymase in vitro resulted in release of SCF into the culture medium. Since
      soluble SCF is thought to regulate mast cell number, the chymase-induced mast
      cell accumulation may occur via the ability of chymase to process membrane-bound
      SCF on the epidermal keratinocytes.

PMID- 11820790
TI  - Proteolipidic vectors for gene transfer to the lung.
AB  - In order to develop improved synthetic gene transfer vectors, we have synthesized
      bifunctional peptides composed of a DNA binding peptide (P2) and ligand peptides
      selected by the phage display technique on tracheal epithelial cells. We have
      evaluated the capacity of these peptides to enhance the gene transfer efficiency
      of the cationic lipid DOTAP to the mouse lung. To optimize the in vivo
      transfection efficiency, we first compared the efficiency of DOTAP to transfect
      the lung by either intravenous injection or aerosolization. We then tested
      DNA/Peptide/DOTAP complexes formed at different Peptide/DNA and DOTAP/DNA charge
      ratios. Under optimal conditions, precompaction of DNA by peptide P2 gave a
      higher expression in the mouse lung using the luciferase reporter gene than
      DOTAP/DNA complexes. A further increase of transfection efficiency was obtained
      with the bifunctional peptide P2-9. Experiments performed with the GFP reporter
      gene showed expression in the alveolar parenchyme.

PMID- 11820791
TI  - Asb4, Ata3, and Dcn are novel imprinted genes identified by high-throughput
      screening using RIKEN cDNA microarray.
AB  - Genes differentially expressed between parthenogenetic and androgenetic embryos
      are candidates for the identification of imprinted genes, which are expressed
      specifically from the maternal or paternal allele. To search for genes
      differentially expressed between parthenogenetic and androgenetic embryos, we
      used the RIKEN full-length enriched mouse cDNA microarray. The 25 candidates
      obtained included 8 known imprinted genes (such as IgfII, Snrpn, and Neuronatin)
      and 3 new ones--Asb4 (ankyrin repeat and SOCS box-containing protein 4), Ata3
      (amino acid transport system A3), and Decorin--which were confirmed by using
      normal diploid embryos from the reciprocal F1 crosses of B6 and JF1 mice. The 25
      candidates also included genes that showed no imprinting-associated expression in
      normal diploid embryos. We describe a feasible high-throughput method of
      screening for novel imprinted genes by using the RIKEN cDNA microarray.

PMID- 11820792
TI  - EGCG attenuates AMPA-induced intracellular calcium increase in hippocampal
      neurons.
AB  - We have investigated the protective effect of (-)-epigallocatechin gallate (EGCG)
      on alpha-amino-3-hydroxy-5-methyl-4-isoxazolo propionate (AMPA)-induced toxicity
      in cultured rat hippocampal neurons. Treatment of 24 h AMPA (10 microM) reduced
      the neuronal viability in both survival neuron counting and MTT reduction assay
      compared with control, with increase in cellular concentrations of hydrogen
      peroxide and malondialdehyde. These responses to AMPA were significantly blocked
      by co-treatments with EGCG (10 microM), which effect was very similar to the
      protective ability of a known antioxidant catalase (2000 U/ml). AMPA (50 microM)
      elicited the increase in intracellular calcium concentration ([Ca(2+)]i) on which
      EGCG significantly attenuated both peak amplitude and sustained nature of that
      [Ca(2+)]i increase in a dose-dependent manner. These data suggest that EGCG has a
      neuroprotective effect against AMPA through inhibition of AMPA-induced [Ca(2+)]i
      increase and consequent attenuation of reactive oxygen species production and
      lipid peroxidation as an antioxidant and a radical scavenger.

PMID- 11820793
TI  - Phosphoenolpyruvate carboxykinase is induced in growth-arrested hepatoma cells.
AB  - Phosphoenolpyruvate carboxykinase (PEPCK) mRNA is elevated in H4IIEC3 rat
      hepatoma cells cultured at high density, suggesting that PEPCK expression and
      growth arrest may be coordinately regulated. Induction of growth arrest either by
      contact inhibition (high culture density) or by serum deprivation correlated with
      significant increases in PEPCK protein and its mRNA. The observation that PEPCK
      mRNA was induced by contact inhibition in the presence of serum indicates that
      the effect of high density is independent of insulin or any other serum
      component. The magnitudes of the changes in PEPCK expression during growth arrest
      were greatly enhanced in KRC-7 cells, an H4IIEC3 subclone that is much more
      sensitive to growth arrest than its parental cell line. Restimulation of
      proliferation in growth-arrested KRC-7 cells, either by addition of serum or
      insulin to serum-deprived cells or by replating contact-inhibited cells at low
      density, caused a rapid decrease in PEPCK expression. However, PEPCK mRNA is not
      always reduced in proliferating cells since treatment of serum-starved cells with
      epidermal growth factor stimulated entry into the cell cycle but did not affect
      PEPCK mRNA levels. Finally, dexamethasone induction of PEPCK mRNA was blunted in
      cells cultured at high density but was unaffected by the presence or absence of
      serum. Collectively, these data suggest the possibility of cross-talk between the
      control of PEPCK expression and growth arrest in KRC-7 cells.

PMID- 11820794
TI  - The basic helix-loop-helix domain of the E47 transcription factor requires other
      protein regions for full DNA binding activity.
AB  - Most transcription factors are believed to be composed of independently
      functioning modules [A. D. Frankel and P. S. Kim (1991) Cell 65, 717-719]. Basic
      helix-loop-helix (bHLH) transcription factors appear to fit this model, with the
      HLH domains mediating dimerization, the basic regions mediating DNA binding, and
      other modules controlling other functions such as transcriptional activation. We
      tested predictions of this model using forced dimers of bHLH proteins including
      E47 homodimers and MyoD:E47 heterodimers and found that protein dimers containing
      complete bHLH domains but lacking other regions of E47 have only 20% of the DNA
      binding ability and transcriptional transactivation activity of wild-type dimers.
      These results demonstrate that the bHLH domains do not function as completely
      independent DNA binding modules. In addition, these results demonstrate that the
      transcriptional activation domains from a single bHLH protein are sufficient to
      activate transcription.

PMID- 11820795
TI  - Angiotensin II reduces macrophage cholesterol efflux: a role for the AT-1
      receptor but not for the ABC1 transporter.
AB  - Impaired cellular cholesterol efflux in cells of the arterial wall is suggested
      to be involved in the pathogenesis of atherosclerosis. Since angiotensin II (Ang
      II) is implicated in the development of atherosclerosis, the aim of the present
      study was to determine whether Ang-II could affect macrophage cholesterol efflux.
      Incubation of increasing concentrations of Ang-II (10(-10)-10(-7) M) with mouse
      peritoneal macrophages that were prelabeled with [3H]cholesterol led to a
      significant decrease in HDL-induced macrophage cholesterol efflux, by up to 70%
      compared to control cells incubated without Ang-II. Ang-II specifically increased
      the plasma membrane unesterified cholesterol content, the substrate for HDL
      induced cholesterol efflux. The inhibitory effect of Ang-II on macrophage
      cholesterol efflux was found to be mediated by the angiotensin II type 1 (AT-1)
      receptor, since addition of the AT-1 antagonist Losartan completely blocked the
      inhibitory effect of Ang-II on the macrophage cholesterol efflux. We thus
      conclude that Ang-II atherogenicity may be related, at least in part, to its
      inhibitory effect on macrophage cholesterol efflux, thus leading to cellular
      cholesterol accumulation, the hallmark of early atherogenesis.

PMID- 11820796
TI  - Hyperlipidemia induced by high cholesterol diet inhibits heat shock response in
      rat hearts.
AB  - We examined whether heat shock response is affected by experimental
      hyperlipidemia in rat hearts. Therefore, isolated hearts of male Wistar rats fed
      a 2% cholesterol-enriched diet or standard diet for 12 weeks were subjected to
      either 20 min heat stress at 42 degrees C or global normothermic ischemia
      followed by 120 min normothermic, normoxic perfusion. Both heat stress and
      ischemia resulted in a significant increase in cardiac mRNA and protein levels of
      the inducible member of the 70-kDa heat shock protein family (HSP70) when
      compared to time-matched controls as assessed by reverse transcriptase polymerase
      chain reaction and Western blotting in hearts of normal rats. However, in
      hyperlipidemic groups, increase in cardiac hsp70 mRNA and HSP70 protein in
      response to heat stress and ischemia was markedly attenuated. We further observed
      that the basal level of hsp70 mRNA was significantly higher in the hyperlipidemic
      group when compared to normal controls; however, the HSP70 protein level was not
      different. This is the first demonstration that hyperlipidemia inhibits cardiac
      heat shock response. We further conclude that basal HSP70 expression might be
      downregulated at a posttranscriptional level in hyperlipidemia.

PMID- 11820797
TI  - Heme oxygenase-1 induction may explain the antioxidant profile of pentaerythrityl
      trinitrate.
AB  - The organic nitrate pentaerythrityl tetranitrate (PETN) is known to exert long
      term antioxidant and antiatherogenic effects by as yet unidentified mechanisms.
      In cultured endothelial cells derived from human umbilical vein, the active PETN
      metabolite PETriN (0.01-1 mM) increased heme oxygenase (HO)-1 mRNA and protein
      levels in a concentration-dependent fashion. HO-1 induction was accompanied by a
      marked increase in catalytic activity of the enzyme as reflected by enhanced
      formation of carbon monoxide and bilirubin. Pretreatment with PETriN or bilirubin
      at low micromolar concentrations protected endothelial cells from hydrogen
      peroxide-mediated toxicity. HO-1 induction and endothelial protection by PETriN
      were not mimicked by isosorbide dinitrate, another long-acting nitrate. The
      present study demonstrates that PETriN stimulates mRNA and protein expression as
      well as enzymatic activity of the antioxidant defense protein HO-1 in endothelial
      cells. Increased HO-1 expression and ensuing formation of cytoprotective
      bilirubin may contribute to and explain the specific antioxidant and
      antiatherogenic actions of PETN.

PMID- 11820798
TI  - Cocaine increases dopamine uptake and cell surface expression of dopamine
      transporters.
AB  - In HEK 293 cells expressing the human dopamine transporter (DAT), a 10-min
      incubation with 10 microM cocaine followed by extensive washing resulted in a 30%
      increase in [3H]dopamine (DA) uptake as well as an increase in cell surface DAT
      in biotinylation experiments. Consistent with this novel regulation, [3H]DA
      uptake into synaptosomes prepared from the nucleus accumbens of rats sacrificed
      30 min after a single cocaine injection (30 mg/kg) was significantly increased
      compared to controls (56% increase in V(max), no change in K(m)). In addition, DA
      clearance in the striatum of anesthetized rats was increased after local
      application of a low (3 pmol) but not high (65 pmol) dose of cocaine, presumably
      as a result of mobilization of DAT to the cell surface. Cocaine-induced increases
      in cell surface expression of DAT and associated changes in DA clearance
      represent a novel mechanism that may play a role in its addictive properties.

PMID- 11820799
TI  - Thrombospondin-1 differentially regulates release of IL-6 and IL-10 by human
      monocytic cell line U937.
AB  - We investigated possible regulatory effects of thrombospondin-1 (TSP-1), a
      multifunctional extracellular matrix protein, on cytokine release from
      macrophages. Immobilized TSP-1 enhanced IL-6 release from the human monocytic
      U937 cells stimulated with phorbol myristate acetate and LPS, whereas it
      inhibited IL-10 release. The 70-kDa fragment of TSP-1 containing the type 1
      repeats showed the same regulatory effects. The enhanced IL-6 release by TSP-1
      was inhibited by anti-CD36 antibody or antibody against the sequence of the
      binding site to CD36 in the type 1 repeats of TSP-1. Conversely, the decrease in
      IL-10 release by TSP-1 was strengthened by the blocking of the interaction
      between CD36 and TSP-1. Furthermore, the involvement of TGF-beta1 in the
      inhibition of IL-10 release by TSP-1 was indicated by the facts that (i) TSP-1
      induced activation of TGF-beta1 produced by the U937 cells, (ii) exogenously
      added TGF-beta1 inhibited IL-10 release, and (iii) antibody against TGF-beta1
      blocked the inhibition of IL-10 release by TSP-1. Together, the present findings
      suggest that TSP-1 enhances IL-6 release from macrophages by interaction with
      CD36, whereas IL-10 release is regulated by the balance between the enhancing
      effect of TSP-1 via CD36 and the suppressive effect by TSP-1-activated TGF-beta1.

PMID- 11820800
TI  - 1 alpha,25-dihydroxyvitamin D3 increases TGF beta 1 binding to human osteoblasts.
AB  - 1alpha,25-Dihydroxyvitamin D3 (1alpha,25(OH)2D3) increases the binding of
      transforming growth factor beta1(TGF beta1) via TGF beta receptors to the surface
      of human osteoblasts. The increase in TGF beta receptors induced by
      1alpha,25(OH)2D3 is dependent on increases in TGF beta secretion induced by
      1alpha,25(OH)2D3, since antibodies directed against TGF beta block the increase
      in TGF beta1 binding. The increase in TGF beta type I and II receptors on cell
      surfaces following 1alpha,25(OH)2D3 treatment is associated with increases in
      receptor mRNA concentrations. Increases in receptor mRNA concentrations following
      1alpha,25(OH)2D3 treatment are not due to changes in receptor gene transcription.
      The role of TGF beta receptors, in mediating the growth responses to
      1alpha,25(OH)2D3 is demonstrated by showing that osteoblasts which express
      dominant negative, kinase-deficient TGF beta type II receptors, fail to respond
      to the growth-inhibitory effects of 1alpha,25(OH)2D3. An increase in TGF beta
      receptor expression is important in mediating 1alpha,25(OH)2D3-associated changes
      in the growth rate of osteoblasts.

PMID- 11820801
TI  - K+ channel cAMP activated in guinea pig gallbladder epithelial cells.
AB  - In guinea pig gallbladder epithelial cells, an increase in intracellular cAMP
      levels elicits the rise of anion channel activity. We investigated by patch-clamp
      techniques whether K(+) channels were also activated. In a cell-attached
      configuration and in the presence of theophylline and forskolin or 8-Br-cAMP in
      the cellular incubation bath, an increase of the open probability (P(o)) values
      for Ca(2+)-activated K(+) channels with a single-channel conductance of about 160
      pS, for inward current, was observed. The increase in P(o) of these channels was
      also seen in an inside-out configuration and in the presence of PKA, ATP, and
      cAMP, but not with cAMP alone; phosphorylation did not influence single-channel
      conductance. In the inside-out configuration, the opioid loperamide (10(-5) M)
      was able to reduce P(o) when it was present either in the microelectrode filling
      solution or on the cytoplasmic side. Detection in the epithelial cells by RT-PCR
      of the mRNA corresponding to the alpha subunit of large-conductance Ca(2+)
      activated K(+) channels (BK(Ca)) indicates that this gallbladder channel could
      belong to the BK family. Immunohistochemistry experiments confirm that these
      cells express the BK alpha subunit, which is located on the apical membrane.
      Other K(+) channels with lower conductance (40 pS) were not activated either by 8
      Br-cAMP (cell-attached) or by PKA + ATP + cAMP (inside-out). These channels were
      insensitive to TEA(+) and loperamide. The data demonstrate that under conditions
      that induce secretion, phosphorylation activates anion channels as well as Ca(2+)
      dependent, loperamide-sensitive K(+) channels present on the apical membrane.

PMID- 11820802
TI  - Analysis of early apoptotic events in individual cells by fluorescence intensity
      and polarization measurements.
AB  - Apoptosis is a dynamic process of variable duration. The ability to continuously
      detect the death process occurring in single or subgroups of cells is therefore
      very important in identifying apoptotic cells within a complex population. The
      Individual Cell Scanner (ICS), a multiparametric, multilaser-based scanning
      static cytometer, was used in the present report for the continuous monitoring of
      the apoptosis process. Fluorescence intensity (FI), polarization (FP), kinetic
      measurements, and cluster analysis of subpopulations were carried out utilizing
      various fluorescent probes. Hydrogen peroxide-induced apoptosis was monitored
      online in intact live lymphocytes by continuous sequential measurements of
      intracellular hyperpolarization. Plasma membrane asymmetry, mitochondrial
      membrane potential, and lysosomal rupture were monitored in individual cells.
      Cytoplasmic condensations, due to cell shrinkage and early lysosomal rupture,
      were found to be very early events of apoptosis. The new analytical capabilities
      suggested here may provide simple and convenient methods for detecting apoptosis
      from its earlier stages.

PMID- 11820803
TI  - Selection of RNA aptamers to the Alzheimer's disease amyloid peptide.
AB  - Alzheimer's disease is correlated with the deposition of amyloid peptides in the
      brain of the patients. The amyloid is thus a major target in the search for novel
      diagnostic and therapeutic approaches. The present work employs in vitro
      selection to develop new tools for the study of the Alzheimer's disease. The
      selection strategy enables the design of specific nucleic acids (aptamers)
      against virtually any target molecule. High-affinity RNA aptamers against the
      betaA4(1-40) were isolated from a combinatorial library of approximately 10(15)
      different molecules. The apparent dissociation constants K(d) of these aptamers
      are 29-48 nM. The binding of the RNA to the amyloid fibrils was confirmed by
      electron microscopy. The chemical synthesis of these nucleic acids enables tailor
      made modifications. By introduction of specific reporter groups these RNAs can
      become suitable tools for analytical and diagnostic purposes. Thus, this study
      may introduce a new approach for diagnosis of the Alzheimer's disease.

PMID- 11820804
TI  - Enhanced activity of the plasma membrane oxidoreductase in circulating
      lymphocytes from insulin-dependent diabetes mellitus patients.
AB  - Circulating human lymphocytes contain a transmembrane oxidoreductase (PMOR)
      capable of reducing dichlorophenol indophenol (DCIP) by endogenous reductants,
      presumably NADH. Membranes from lymphocytes obtained from buffy coats contain a
      NADH DCIP reductase having a K(m) of about 1 microM and almost insensible to
      dicoumarol. The PMOR of lymphocytes from insulin-dependent diabetic patients is
      higher than that from age-matched controls and, in addition, has a dicoumarol
      sensitive component, lacking in most controls, presumably due to membrane
      association of DT-diaphorase. The increase of PMOR in diabetes is likely due to
      overexpression of the enzyme, in view of the very low K(m) for NADH indicating
      that, in intact cells, the enzyme is practically saturated with the reductant
      substrate.

PMID- 11820805
TI  - Sequence analysis of the entire mitochondrial genome in Parkinson's disease.
AB  - The pathogenesis of Parkinson's disease (PD) is largely unknown. Indirect
      evidence suggests that mutations in mitochondrial DNA (mtDNA) might play a role,
      but previous studies have not consistently associated any specific mutations with
      PD. However, these studies have generally been confined to limited areas of the
      mitochondrial genome. We therefore sequenced the entire mitochondrial genome from
      substantia nigra of 8 PD and 9 control subjects. Several sequence variants were
      distributed differently between PD and control subjects, but all were previously
      reported polymorphisms. Several secondary LHON mutations were found, as well as a
      number of novel missense mutations, but all were rare and did not differ between
      PD and control subjects. Finally, PD and control subjects did not differ in the
      total number of all mutations, nor the total number of missense mutations. Thus,
      mtDNA involvement in PD, if any, is likely to be complex and should be
      reconsidered carefully.

PMID- 11820806
TI  - Structural investigation of the hedamycin:d(ACCGGT)2 complex by NMR and
      restrained molecular dynamics.
AB  - Hedamycin, a member of the pluramycin family of drugs, displays a range of
      biological responses including antitumor and antimicrobial activity. The
      mechanism of action is via direct interaction with DNA through intercalation
      between the bases of the oligonucleotide and alkylation of a guanine residue at
      5'-PyG-3' sites. There appears to be some minor structural differences between
      two earlier studies on the interaction of hedamycin with 5'-PyG-3' sites. In this
      study, a high-resolution NMR analysis of the hedamycin:d(ACCGGT)2 complex was
      undertaken in order to investigate the effect of replacing the thymine with a
      guanine at the preferred 5'-CGT-3' site. The resultant structure was compared
      with earlier work, with particular emphasis placed on the drug conformation. The
      structure of the hedamycin:d(ACCGGT)2 complex has many features in common with
      the two previous NMR structures of hedamycin:DNA complexes but differed in the
      conformation and orientation of the N,N-dimethylvancosamine saccharide of
      hedamycin in one of these structures. The preferential binding of hedamycin to 5'
      CG-3' over 5'-TG-3' binding sites is explained in terms of the orientation and
      location of the N,N-dimethylvancosamine saccharide in the minor groove.

PMID- 11820808
TI  - Gene transfer into zebrafish by sperm nuclear transplantation.
AB  - A technique for fertilizing zebrafish eggs by injection of sperm nuclei is
      described. Eggs that cleave normally can develop into swimming larvae and give
      rise to fertile adults. If sperm nuclei are preincubated for 20 min with DNA
      encoding the green fluorescent protein, transgene expression can be detected in
      all cells of the embryo. The use of condensed sperm nuclei allows injection with
      a small bore pipette, which is critical for successful injection of the
      relatively small zebrafish egg. This technique enables the generation of
      ubiquitously expressing transgenic zebrafish directly by microinjection. Hence,
      experiments involving transgenic fish can be completed in days, without the need
      for growing and breeding founders. This technique may also be used to generate
      transgenic lines, as transgene expression was visible in the offspring of
      transgenic founders. The method described here is likely to be applicable to
      other teleosts, such as medaka and salmon.

PMID- 11820807
TI  - Increased expression of thyroid transcription factor-1 (TTF-1) in respiratory
      epithelial cells inhibits alveolarization and causes pulmonary inflammation.
AB  - Thyroid transcription factor-1 (TTF-1), a member of the Nkx2 family of
      homeodomain-containing transcription factors, is expressed in the epithelium of
      the lung. TTF-1 is a critical regulator of transcription for the surfactant
      proteins (SP) A, B, and C and is essential for lung morphogenesis. Sites and
      levels of TTF-1 expression vary during lung morphogenesis and following injury.
      In order to determine the role of TTF-1 in lung formation, transgenic mice were
      generated in which TTF-1 was expressed in respiratory epithelial cells of wild
      type and Ttf1 null mutant (-/-) mice, using the lung-specific SP-C promoter. The
      SP-C-Ttf1 transgene did not rescue the severe pulmonary hypoplasia characteristic
      of the Ttf1 (-/-) mice. Increased expression of TTF-1, however, caused dose
      dependent alterations in postnatal lung morphology of wild-type mice. Modest
      overexpression of TTF-1 caused type II cell hyperplasia and increased the
      cellular content of SP-B. In contrast, higher expression levels of TTF-1
      disrupted alveolar septation, causing emphysema. In mice with the highest
      transgene expression, TTF-1 caused severe inflammation, pulmonary fibrosis,
      respiratory failure, and death, associated with eosinophil infiltration and
      increased expression of eotaxin and IL-6. Increased expression of TTF-1 altered
      alveolarization and caused chronic pulmonary inflammation, demonstrating that
      precise regulation of TTF-1 is critical for homeostasis in the postnatal lung.

PMID- 11820809
TI  - Conserved regulation of the Caenorhabditis elegans labial/Hox1 gene ceh-13.
AB  - Caenorhabditis elegans contains a set of six cluster-type homeobox (Hox) genes
      that are required during larval development. Some of them, but unlike in flies
      not all of them, are also required during embryogenesis. It has been suggested
      that the control of the embryonic expression of the worm Hox genes might differ
      from that of other species by being regulated in a lineal rather than a regional
      mode. Here, we present a trans-species analysis of the cis-regulatory region of
      ceh-13, the worm ortholog of the Drosophila labial and the vertebrate Hox1 genes,
      and find that the molecular mechanisms that regulate its expression may be
      similar to what has been found in species that follow a regulative, non-cell
      autonomous mode of development. We have identified two enhancer fragments that
      are involved in different aspects of the embryonic ceh-13 expression pattern. We
      show that important features of comma-stage expression depend on an
      autoregulatory input that requires ceh-13 and ceh-20 functions. Our data show
      that the molecular nature of Hox1 class gene autoregulation has been conserved
      between worms, flies, and vertebrates. The second regulatory sequence is
      sufficient to drive correct early embryonic expression of ceh-13. Interestingly,
      this enhancer fragment acts as a response element of the Wnt/WG signaling pathway
      in Drosophila embryos.

PMID- 11820810
TI  - Mesendoderm extension and mantle closure in Xenopus laevis gastrulation: combined
      roles for integrin alpha(5)beta(1), fibronectin, and tissue geometry.
AB  - We describe mesendoderm morphogenesis during gastrulation in the frog Xenopus
      laevis and investigate the mechanics of these movements with tissue explants.
      When a dorsal marginal zone explant is plated onto fibronectin, the mesendoderm
      moves away from the dorsal axial tissues as an intact sheet. Mesendodermal cells
      within these explants display monopolar protrusive activity and radially
      intercalate during explant extension. Live time-lapse confocal sequences of actin
      dynamics at the margin of these extending explants prompt us to propose that
      integrin-mediated traction drives these movements. We demonstrate that integrin
      alpha(5)beta(1) recognition of the synergy site located within the type III(9)
      repeat of fibronectin is required for mesendoderm extension. Normal mesendoderm
      morphogenesis occurs with a unique "cup-shaped" geometry of the extending
      mesendodermal mantle and coincides with a higher rate of tissue extension than
      that seen in the simpler dorsal marginal zone explant. These higher rates can be
      reconstituted with "in-the-round" configurations of several explants. We propose
      several mechanically based hypotheses to explain both the initial fibronectin
      dependent extension of the mesendoderm and additional requirement of tissue
      geometry during the high-velocity closure of the mesendodermal mantle.

PMID- 11820811
TI  - Sonic hedgehog inhibits the terminal differentiation of limb myoblasts committed
      to the slow muscle lineage.
AB  - The proliferation, differentiation, and fusion of a small number of myogenic
      precursor cells must be precisely regulated during development to ensure the
      proper size, organization, and function of the limb musculature. We have examined
      the role of Sonic hedgehog (Shh) in these processes by both augmentation and
      inhibition of the Shh-mediated signaling pathway. Our data show that Shh
      regulates muscle development by repressing the terminal differentiation of early
      myogenic precursor cells and does not function as a myoblast mitogen. Shh
      function in hypaxial muscle appears to be spatially restricted to the early
      myoblast population within the ventral muscles of the posterior region of the
      limb. Furthermore, Shh appears to act as a permissive, rather than an inductive,
      signal for slow MyHC expression in myoblasts. Our data thus provide the
      foundation for a new hypothesis for Shh function in hypaxial skeletal muscle
      development.

PMID- 11820813
TI  - The UCU1 Arabidopsis gene encodes a SHAGGY/GSK3-like kinase required for cell
      expansion along the proximodistal axis.
AB  - Most signal transduction pathways central to development are not shared by plants
      and animals. Such is the case of the Wingless/Wnt signaling pathway, whose
      components play key roles in metazoan pattern formation and tumorigenesis, but
      are absent in plants, with the exception of SHAGGY/GSK3, a cytoplasmic protein
      kinase represented in the genome of Arabidopsis thaliana by a family of 10 AtSK
      genes for which mutational evidence is scarce. Here, we describe the
      characterization of mutant alleles of the Arabidopsis ULTRACURVATA1 (UCU1) gene,
      the two strongest of which dramatically reduce cell expansion along the
      proximodistal axis, dwarfing the mutant plants, whose cells expand properly
      across but not along most organs. Proximodistal expansion of adaxial (dorsal) and
      abaxial (ventral) leaf cells exhibits a differential dependence on UCU1 function,
      as suggested by the leaves of ucu1 mutants, which are rolled spirally downward in
      a circinate manner. We have positionally cloned the UCU1 gene, which encodes an
      AtSK protein involved in the cross-talk between auxin and brassinosteroid
      signaling pathways, as indicated by the responses of ucu1 mutants to plant
      hormones and the phenotypes of double mutants involving ucu1 alleles.

PMID- 11820815
TI  - Gene expression profiles in tadpole larvae of Ciona intestinalis.
AB  - A set of 12,779 expressed sequence tags (ESTs), both the 5'-most and 3'-most
      ends, derived from Ciona intestinalis tadpole larvae was categorized into 3521
      independent clusters, from which 1013 clusters corresponding to 9424 clones were
      randomly selected to analyze genetic information and gene expression profiles.
      When compared with sequences in databases, 545 of the clusters showed significant
      matches (P < E-15) with reported proteins, while 153 showed matches with putative
      proteins for which there is not enough information to categorize their function,
      and 315 had no significant sequence similarities to known proteins. Sequence
      similarity analyses of the 545 clusters in relation to the biological functions
      demonstrated that 407 of them have functions that many kinds of cells use, 104
      are associated with cell-cell communication, and 34 are transcription factors or
      other gene-regulatory proteins. Sequence prevalence distribution analysis
      demonstrated that more than one-half of the mRNAs are rare mRNAs. All of the 1013
      clusters were subjected to whole-mount in situ hybridization to analyze the gene
      expression profile in the tadpole larva. A total of 361 clusters showed
      expression specific to a certain tissue or organ: 96 showed epidermis-specific
      expression, 60 were specific to the nervous system, 108 to endoderm, 34 to
      mesenchyme, 5 to trunk lateral cells, 4 to trunk ventral cells, 23 to notochord,
      28 to muscle, and 3 to siphon rudiments. In addition, 190 clusters showed
      expression in multiple tissues. Moreover, nervous system-specific genes showed
      intriguing expression patterns dependent on the cluster. The present study
      highlights a broad spectrum of genes that are used in the formation of one of the
      most primitive chordate body plans as well as for the function of various types
      of tissue and organ and also provides molecular markers for individual tissues
      and organs constituting the Ciona larva.

PMID- 11820812
TI  - The Zebrafish trilobite gene is essential for tangential migration of
      branchiomotor neurons.
AB  - Newborn neurons migrate extensively in the radial and tangential directions to
      organize the developing vertebrate nervous system. We show here that mutations in
      zebrafish trilobite (tri) that affect gastrulation-associated cell movements also
      eliminate tangential migration of motor neurons in the hindbrain. In the wild
      type hindbrain, facial (nVII) and glossopharyngeal (nIX) motor neurons are
      induced in rhombomeres 4 and 6, respectively, and migrate tangentially into r6
      and r7 (nVII) and r7 (nIX). In all three tri alleles examined, although normal
      numbers of motor neurons are induced, nVII motor neurons are found exclusively in
      r4, and nIX-like motor neurons are found exclusively in r6. The migration of
      other neuronal and nonneuronal cell types is unaffected in tri mutants.
      Rhombomere formation and the development of other hindbrain neurons are also
      unaffected in tri mutants. Furthermore, tangential neuronal migration occurs
      normally in the gastrulation mutant knypek, indicating that the trilobite neuron
      phenotype does not arise nonspecifically from aberrant gastrulation-associated
      movements. We conclude that trilobite function is specifically required for two
      types of cell migration that occur at different stages of zebrafish development.

PMID- 11820814
TI  - The mouse meiotic mutation mei1 disrupts chromosome synapsis with sexually
      dimorphic consequences for meiotic progression.
AB  - mei1 (meiosis defective 1) is the first meiotic mutation in mice derived by
      phenotype-driven mutagenesis. It was isolated by using a novel technology in
      which embryonic stem (ES) cells were chemically mutagenized and used to generate
      families of mice that were screened for infertility. We report here that
      mei1/mei1 spermatocytes arrest at the zygotene stage of meiosis I, exhibiting
      failure of homologous chromosomes to properly synapse. Notably, RAD51 failed to
      associate with meiotic chromosomes in mutant spermatocytes, despite evidence for
      the presence of chromosomal breaks. Transcription of genes that are markers for
      the leptotene and zygotene stages, but not genes that are markers for the
      pachytene stage, was observed. mei1/mei1 females are sterile, and their oocytes
      also show severe synapsis defects. Nevertheless, unlike arrested spermatocytes, a
      small number of mutant oocytes proved capable of progressing to metaphase I and
      attempting the first meiotic division. However, their chromosomes were unpaired
      and were not organized properly at the metaphase plate or along the spindle
      fibers during segregation. mei1 was genetically mapped to chromosome (Chr) 15 in
      an interval that is syntenic to human Chr 22q13. This region, which has been
      completely sequenced, contains no known homologs of genes specifically required
      for meiosis in model organisms. Thus, mei1 may be a novel meiotic gene.

PMID- 11820816
TI  - Otx2 is required to respond to signals from anterior neural ridge for forebrain
      specification.
AB  - Previous analysis employing chimeric and transgenic rescue experiments has
      suggested that Otx2 is required in the neuroectoderm for development of the
      forebrain region. In order to elucidate the precise role of Otx2 in forebrain
      development, we attempted to generate an allelic series of Otx2 mutations by Flp-
      and Cre-mediated recombination for the production of conditional knock-out mice.
      Unexpectedly, the neo-cassette insertion created a hypomorphic Otx2 allele;
      consequently, the phenotype of compound mutant embryos carrying both a
      hypomorphic and a null allele (Otx2(frt-neo/-)) was analyzed. Otx2(frt-neo/-)
      mutant mice died at birth, displaying rostral head malformations. Molecular
      marker analysis demonstrated that Otx2(frt-neo/-) mutant embryos appeared to
      undergo anterior-posterior axis generation and induction of anterior
      neuroectoderm normally; however, these mutants subsequently failed to correctly
      specify the forebrain region. As the rostral margin of the neural plate, termed
      the anterior neural ridge (ANR), plays crucial roles with respect to neural plate
      specification, we examined expression of molecular markers for the ANR and the
      neural plate; moreover, neural plate explant studies were performed. Analyses
      revealed that telencephalic gene expression did not occur in mutant embryos due
      to defects of the neural plate; however, the mutant ANR bore normal induction
      activity on gene expression. These results further suggest that Otx2 dosage may
      be crucial in the neural plate with respect to response to inductive signals
      primarily from the ANR for forebrain specification.

PMID- 11820817
TI  - Distinct consequences of sterol sensor mutations in Drosophila and mouse patched
      homologs.
AB  - The membrane protein Patched (Ptc) is a critical regulator of Hedgehog signaling.
      Ptc is among a family of proteins that contain a sterol sensor motif. The
      function of this domain is poorly understood, but some proteins that contain
      sterol sensors are involved in cholesterol homeostasis. In the SREBP cleavage
      activating protein (SCAP), sterols inhibit the protein's activity through this
      domain. Mutations in two highly conserved residues in the SCAP sterol sensor have
      been identified that confer resistance to sterol regulation. We introduced the
      analogous mutations in the sterol sensor motif of fly Ptc and mouse Ptc1 and
      examined their effect on protein activity. In contrast to SCAP, the sterol sensor
      mutations had different affects on Drosophila Ptc; Ptc Y442C retained function,
      while Ptc D584N conferred dominant negative activity. In the wing imaginal disc,
      Ptc D584N overexpression induced Hedgehog targets by stabilizing Cubitus
      interruptus and inducing decapentaplegic. However, Ptc D584N did not induce
      collier, a gene that requires high levels of Hedgehog signaling. In mouse Ptc1,
      the Y438C and D585N mutations did not stimulate signaling in Shh-responsive cell
      lines but did complement murine ptc1(-/-) cells. The results suggest that
      mutations in sterol sensor motifs alter function differently between sterol
      sensor family members.

PMID- 11820818
TI  - CABYR, a novel calcium-binding tyrosine phosphorylation-regulated fibrous sheath
      protein involved in capacitation.
AB  - To reach fertilization competence, sperm undergo an incompletely understood
      series of morphological and molecular maturational processes, termed
      capacitation, involving, among other processes, protein tyrosine phosphorylation
      and increased intracellular calcium. Hyperactivated motility and an ability to
      undergo the acrosome reaction serve as physiological end points to assess
      successful capacitation. We report here that acidic (pI 4.0) 86-kDa isoforms of a
      novel, polymorphic, testis-specific protein, designated calcium-binding tyrosine
      phosphorylation-regulated protein (CABYR), were tyrosine phosphorylated during in
      vitro capacitation and bound (45)Ca on 2D gels. Acidic 86-kDa calcium-binding
      forms of CABYR increased during in vitro capacitation, and calcium binding to
      these acidic forms was abolished by dephosphorylation with alkaline phosphatase.
      Six variants of CABYR containing two coding regions (CR-A and CR-B) were cloned
      from human testis cDNA libraries, including five variants with alternative splice
      deletions. A motif homologous to the RII dimerization domain of PK-A was present
      in the N-terminus of CR-A in four CABYR variants. A single putative EF handlike
      motif was noted in CR-A at aas 197-209, while seven potential tyrosine
      phosphorylation-like sites were noted in CR-A and four in CR-B. Pro-X-X-Pro
      (PXXP) modules were identified in the N- and C-termini of CR-A and CR-B. CABYR
      localizes to the principal piece of the human sperm flagellum in association with
      the fibrous sheath and is the first demonstration of a sperm protein that gains
      calcium-binding capacity when phosphorylated during capacitation.

PMID- 11820819
TI  - Regulation of stage-specific nuclear translocation of Dnmt1o during
      preimplantation mouse development.
AB  - DNA methylation of CpG dinucleotides by DNA methyltransferase 1 is implicated in
      the regulation of transcription and, in particular, the transcription of
      imprinted genes. Although the oocyte-specific form of Dnmt1 (Dnmt1o) possesses a
      functional nuclear localization signal, it is predominantly localized in the
      cytoplasm of the oocyte and preimplantation mouse embryo but undergoes a
      transient nuclear localization during the eight-cell stage, when the embryos
      undergo compaction. We report here that Dnmt1o is likely retained in the
      cytoplasm by an active process, since approximately 70% of DNA methyltransferase
      activity is retained following permeabilization procedures that result in the
      release of approximately 75% of oocyte/embryo protein. Treatment of the embryos
      with agents that disrupt either microfilaments or microtubules has little, if
      any, effect on the retention of Dnmt1o in permeabilized embryos. While Dnmt1o
      does not colocalize with either mitochondria or endoplasmic reticulum, it does
      colocalize with annexin V, which is known to interact with Dnmt1o. We also report
      that the timing of nuclear entry of Dnmt1o during the eight-cell stage is
      independent of DNA replication, transcription, and protein synthesis, as well as
      compaction, cell contact, and cytokinesis. The time of nuclear entry, therefore,
      appears linked to the time following fertilization, which suggests that a
      molecular clock governs the time of nuclear import.

PMID- 11820820
TI  - Quantification of human brain metabolites from in vivo 1H NMR magnitude spectra
      using automated artificial neural network analysis.
AB  - Long echo time (TE=270 ms) in vivo proton NMR spectra resembling human brain
      metabolite patterns were simulated for lineshape fitting (LF) and quantitative
      artificial neural network (ANN) analyses. A set of experimental in vivo 1H NMR
      spectra were first analyzed by the LF method to match the signal-to-noise ratios
      and linewidths of simulated spectra to those in the experimental data. The
      performance of constructed ANNs was compared for the peak area determinations of
      choline-containing compounds (Cho), total creatine (Cr), and N-acetyl aspartate
      (NAA) signals using both manually phase-corrected and magnitude spectra as
      inputs. The peak area data from ANN and LF analyses for simulated spectra yielded
      high correlation coefficients demonstrating that the peak areas quantified with
      ANN gave similar results as LF analysis. Thus, a fully automated ANN method based
      on magnitude spectra has demonstrated potential for quantification of in vivo
      metabolites from long echo time spectroscopic imaging.

PMID- 11820822
TI  - Temperature-induced changes in the EPR spectrum of the magnetic center in kaolin.
AB  - Studies of kaolin have revealed an effect characterized by an unusual temperature
      induced change of the EPR spectrum of the Fe3+ ion, which is the magnetic probe
      in kaolin-clay. At low temperature (T=4.2 K) a resonance line with an effective g
      value g1=4.13 +/- 0.16 is observed. At high temperature (T=288 K) one observes a
      resonance line with the effective g-value g2=2.15 +/- 0.1. The transition from
      the low- to high-temperature spectrum is gradual and it is accompanied by a
      redistribution of the absorption intensity. The observed properties of the
      temperature dependence of the EPR spectrum are characteristic of systems with a
      multiminimum potential.

PMID- 11820821
TI  - Kinetic measurements using EPR imaging with a modulated field gradient.
AB  - EPR imaging with modulated field gradient was applied for the investigation of
      fast diffusion processes. Three different imaging methods are possible: spectral
      temporal, spatio-temporal, and spectral-spatial imaging. The time resolution is
      on the order of seconds and the spatial resolution is in the micrometer region.
      The efficiency of this imaging technique is demonstrated for the penetration of
      the spin probe Tempol in the skin of hairless mice biopsies. The skin is normally
      protected against the penetration of water soluble substances by the horny layer,
      a resistive thin lipophilic layer. Overcoming this horny layer for water soluble
      ingredients is one of the main practical problems for the topical application of
      pharmaceutics which could be investigated by EPR imaging. Different images
      represent the penetration behavior of the water soluble Tempol in the skin after
      treatment with the penetration enhancer DMSO (Dimethylsulfoxide) and after
      removing the horny layer.

PMID- 11820823
TI  - MR detection of mechanical vibrations using a radiofrequency field gradient.
AB  - A new method for NMR characterization of mechanical waves, based upon
      radiofrequency field gradient for motion encoding, is proposed. A binomial B1
      gradient excitation scheme was used to visualize the mobile spins undergoing a
      periodic transverse mechanical excitation. A simple model was designed to
      simulate the NMR signal as a function of the wave frequency excitation and the
      periodicity of the NMR pulse sequence. The preliminary results were obtained on a
      gel phantom at low vibration frequencies (0-200 Hz) by using a ladder-shaped coil
      generating a nearly constant RF field gradient along a specific known direction.
      For very small displacements and/or B1 gradients, the NMR signal measured on a
      gel phantom was proportional to the vibration amplitude and the pulse sequence
      was shown to be selective with respect to the vibration frequency. A good
      estimation of the direction of vibrations was obtained by varying the angle
      between the motion direction and the B1 gradient. The method and its use in
      parallel to more conventional MR elastography techniques are discussed. The
      presented approach might be of interest for noninvasive investigation of elastic
      properties of soft tissues and other materials.

PMID- 11820824
TI  - Specification and visualization of anisotropic interaction tensors in
      polypeptides and numerical simulations in biological solid-state NMR.
AB  - Software facilitating numerical simulation of solid-state NMR experiments on
      polypeptides is presented. The Tcl-controlled SIMMOL program reads in atomic
      coordinates in the PDB format from which it generates typical or user-defined
      parameters for the chemical shift, J coupling, quadrupolar coupling, and dipolar
      coupling tensors. The output is a spin system file for numerical simulations,
      e.g., using SIMPSON (Bak, Rasmussen, and Nielsen, J. Magn. Reson. 147, 296
      (2000)), as well as a 3D visualization of the molecular structure, or selected
      parts of this, with user-controlled representation of relevant tensors, bonds,
      atoms, peptide planes, and coordinate systems. The combination of SIMPSON and
      SIMMOL allows straightforward simulation of the response of advanced solid-state
      NMR experiments on typical nuclear spin interactions present in polypeptides.
      Thus, SIMMOL may be considered a "sample changer" to the SIMPSON "computer
      spectrometer" and proves to be very useful for the design and optimization of
      pulse sequences for application on uniformly or extensively isotope-labeled
      peptides where multiple-spin interactions need to be considered. These aspects
      are demonstrated by optimization and simulation of novel DCP and C7 based 2D
      N(CO)CA, N(CA)CB, and N(CA)CX MAS correlation experiments for multiple-spin
      clusters in ubiquitin and by simulation of PISA wheels from PISEMA spectra of
      uniaxially oriented bacteriorhodopsin and rhodopsin under conditions of finite RF
      pulses and multiple spin interactions.

PMID- 11820826
TI  - Localized proton spectroscopy without water suppression: removal of gradient
      induced frequency modulations by modulus signal selection.
AB  - Most Magnetic Resonance Spectroscopy (MRS) localization methods can generate
      gradient vibrations at acoustic frequencies and/or magnetic field oscillation,
      which can cause a time-varying magnetic field superimposed onto the static one.
      This effect can produce frequency modulations of the spectral resonances. When
      localized MRS data are acquired without water suppression, the associated
      frequency modulations are manifested as a manifold of spurious peaks, called
      sidebands, which occur symmetrically around the water resonance. These sidebands
      can be larger than the small metabolite resonances and can present a problem for
      the quantitation of the spectra, especially at short echo times. Furthermore, the
      resonance lineshapes may be distorted if any low frequency modulations are
      present. A simple solution is presented which consists of selecting the modulus
      of the acquired Free Induction Decay (FID) signal. Since the frequency
      modulations affect only the phase of the FID signal, the obtained real spectrum
      of the modulus is free from the spurious peaks where quantitative results may be
      directly obtained. Using this method, the distortions caused by the sidebands are
      removed. This is demonstrated by processing proton MRS spectra acquired without
      water suppression collected from a phantom containing metabolites at
      concentrations comparable to those in human brain and from a human subject using
      two different localization methods (PRESS and Chemical Shift Imaging PRESS
      (CSI)). The results obtained illustrate the ability of this approach to remove
      the spurious peaks. The corrected spectra can then be fit accurately. This is
      confirmed by the results obtained from both the relative and the absolute
      metabolites concentrations in phantoms and in vivo.

PMID- 11820825
TI  - Relative CSA-dipolar orientation from REDOR sidebands.
AB  - Algebraic expressions are given for the sideband intensities of REDOR dephasing
      experiments as a function of the relative orientation of the CSA and dipolar
      tensors. The expressions are straightforward to derive and implement and can be
      easily modified for variations in the spin systems, including distributions of
      distances and multiple dephasers. These expressions, along with the high
      sensitivity, resolution, and general robust nature of REDOR, make determining CSA
      dipolar orientations from REDOR experiments reliable and, compared to full
      simulations, efficient and routine. Additionally, it is shown that even the +/-1
      sidebands of fast-spinning samples may contain significant information about
      orientation. Finally, numerical integration of the expressions supports the
      intuitive notion that any difference in the sideband dephasing rates is evidence
      of preferred CSA-dipolar orientations. This fact can be used to gauge the extent
      of local molecular order in intermolecular dephasing experiments.

PMID- 11820827
TI  - NMR of multipolar spin states excitated in strongly inhomogeneous magnetic
      fields.
AB  - The possibility of exciting and filtering various multipolar spin states in
      proton NMR like dipolar encoded longitudinal magnetization (LM), double-quantum
      (DQ) coherences, and dipolar order (DO) in strongly inhomogeneous static and
      radio-frequency magnetic fields is investigated. For this purpose pulse sequences
      which label and manipulate the multipolar spin states in a specific way were
      implemented on the NMR-MOUSE (mobile universal surface explorer). The performance
      of the pulse sequences was also tested in homogeneous fields on a solid-state
      high-field NMR spectrometer. The theoretical justification of these procedures
      was shown for a rigid two-spin 1/2 system coupled by dipolar interactions.
      Dipolar encoded longitudinal magnetization decay curves, double-quantum and
      dipolar-order buildup curves, as well as double-quantum decay curves were
      recorded with the NMR-MOUSE for natural rubber samples with different crosslink
      density. The possibility of using these multipolar spin states for investigations
      of strained elastomers by NMR-MOUSE is also shown. These curves give access to
      quantitative values of the ratio of the total residual dipolar couplings of the
      protons in the series of samples which are in good agreement with those measured
      in homogeneous fields.

PMID- 11820828
TI  - Coherent excitation with phase-incremented pulses.
AB  - An outline is given for calculating the evolution of a spin system by a pulse
      sequence with phase-incremented pulses (PIPs). It is done in a frame with a speed
      of 2pideltaf=deltaphi/deltatau relative to the rotating frame, where deltaphi and
      deltatau are the phase- and time-increment of the PIP. This particular frame is
      defined as the eigenframe, in which the phase of the PIP for the center band is
      stationary and is subjected to a universal phase shift (UPS=-deltaphi/2), and the
      strength of the PIP is scaled by a factor of lambda=2[1
      cos(deltaphi)]/(deltaphi). The phase differences between different eigenframes
      can be attributed to the initial phases of the PIPs, making it possible to use
      the Bloch vector model even in different eigenframes. A new way is provided to
      construct composite pulses with not only amplitude and phase modulations but also
      offset modulation. Several examples, including a broadband inversion pulse, a
      Hahn spin echo, and a selective inversion and null pulse, all composed of PIPs,
      are discussed in detail.

PMID- 11820830
TI  - A continuous tensor field approximation of discrete DT-MRI data for extracting
      microstructural and architectural features of tissue.
AB  - The effective diffusion tensor of water, D, measured by diffusion tensor MRI (DT
      MRI), is inherently a discrete, noisy, voxel-averaged sample of an underlying
      macroscopic effective diffusion tensor field, D(x). Within fibrous tissues this
      field is presumed to be continuous and smooth at a gross anatomical length scale.
      Here a new, general mathematical framework is proposed that uses measured DT-MRI
      data to produce a continuous approximation to D(x). One essential finding is that
      the continuous tensor field representation can be constructed by repeatedly
      performing one-dimensional B-spline transforms of the DT-MRI data. The fidelity
      and noise-immunity of this approximation are tested using a set of synthetically
      generated tensor fields to which background noise is added via Monte Carlo
      methods. Generally, these tensor field templates are reproduced faithfully except
      at boundaries where diffusion properties change discontinuously or where the
      tensor field is not microscopically homogeneous. Away from such regions, the
      tensor field approximation does not introduce bias in useful DT-MRI parameters,
      such as Trace(D(x)). It also facilitates the calculation of several new
      parameters, particularly differential quantities obtained from the tensor of
      spatial gradients of D(x). As an example, we show that they can identify tissue
      boundaries across which diffusion properties change rapidly using in vivo human
      brain data. One important application of this methodology is to improve the
      reliability and robustness of DT-MRI fiber tractography.

PMID- 11820829
TI  - Frequency dependence of EPR signal intensity, 248 MHz to 1.4 GHz.
AB  - The electron paramagnetic resonance pulsed free induction decay (FID) of a
      degassed solution of a triaryl methyl radical, methyl tris(8-carboxy-2,2,6,6
      tetramethyl(-d3)-benzo[1,2-d:4,5-d']bis(1,3)dithiol-4-yl) tripotassium salt, 0.2
      mM in H2O, was measured at VHF (247.5 MHz) and L-band (1.40 GHz). The calculated
      and observed FID signal amplitudes (in millivolts) agreed within 1 and 6%, and
      the ratio of the normalized FID signals at the two frequencies agreed within 5%.
      The FID decay time constant was 2.7 micros at both frequencies.

PMID- 11820831
TI  - Rotor-encoded heteronuclear MQ MAS NMR spectroscopy of half-integer quadrupolar
      and spin I=1/2 nuclei.
AB  - A new two-dimensional heteronuclear multiple-quantum magic-angle spinning (MQ
      MAS) experiment is presented which combines high resolution for the half-integer
      quadrupolar nucleus with information about the dipolar coupling between the
      quadrupolar nucleus and a spin I=1/2 nucleus. Homonuclear MQ coherence is
      initially created for the half-integer quadrupolar nucleus by a single pulse as
      in a standard MQ MAS experiment. REDOR recoupling of the heteronuclear dipolar
      coupling then allows the creation of a heteronuclear multiple-quantum coherence
      comprising multiple- and single-quantum coherence of the quadrupolar and spin
      I=1/2 nucleus, respectively, which evolves during t1. Provided that the t1
      increment is not rotor synchronized, rotor-encoded spinning-sideband patterns are
      observed in the indirect dimension. Simulated spectra for an isolated IS spin
      pair show that these patterns depend on the recoupling time, the magnitude of the
      dipolar coupling, the quadrupolar parameters, as well as the relative orientation
      of the quadrupolar and dipolar principal axes systems. Spectra are presented for
      Na2HPO4, with the heteronuclear 23Na-1HMQ MAS experiments beginning with the
      excitation of 23Na (spin I=3/2) three-quantum coherence. Coherence counting
      experiments demonstrate that four- and two-quantum coherences evolve during t1.
      The heteronuclear spinning-sideband patterns observed for the three-spin H-Na-H
      system associated with the Na(2) site are analyzed. For an IS2 system, simulated
      spectra show that, considering the free parameters, the spinning-sideband
      patterns are particularly sensitive to only, first, the angle between the two IS
      internuclear vectors and, second, the two heteronuclear dipolar couplings. It is
      demonstrated that the proton localization around the Na(2) site according to the
      literature crystal structure of Na2HPO4 is erroneous. Instead, the experimental
      data is consistent with two alternative different structural arrangements,
      whereby either there is a deviation of 10 degrees from linearity for the case of
      two identical Na-H distances, or there is a linear arrangement, but the two Na-H
      distances are different. Furthermore, the question of the origin of spinning
      sidebands in the (homonuclear) MQ MAS experiment is revisited. It is shown that
      the asymmetric experimental MQ sideband pattern observed for the low-C(Q) Na(2)
      site in Na(2)HPO4 can only be explained by considering the 23Na chemical shift
      anisotropy.

PMID- 11820832
TI  - NMR spin locking of proton magnetization under a frequency-switched Lee-Goldburg
      pulse sequence.
AB  - The spin dynamics of NMR spin locking of proton magnetization under a frequency
      switched Lee-Goldburg (FSLG) pulse sequence is investigated for a better
      understanding of the line-narrowing mechanism in PISEMA experiments. For the
      sample of oriented 15N(1,3,5,7)-labeled gramicidin A in hydrated DMPC bilayers,
      it is found that the spin-lattice relaxation time T(1rho)(H) in the tilted
      rotating frame is about five times shorter when the 1H magnetization is spin
      locked at the magic angle by the FSLG sequence compared to the simple Lee
      Goldburg sequence. It is believed that the rapid phase alternation of the
      effective fields during the FSLG cycles results in averaging of the spin lock
      field so that the spin lock becomes less efficient. A FSLG supercycle has been
      suggested here to slow the phase alternation. It has been demonstrated
      experimentally that a modified PISEMA pulse sequence with such supercycles gives
      rise to about 30% line narrowing in the dipolar dimension in the PISEMA spectra
      compared to a standard PISEMA pulse sequence.

PMID- 11820834
TI  - Sizing of emulsion droplets under flow using flow-compensating NMR-PFG
      techniques.
AB  - Using the nuclear magnetic resonance (NMR) pulsed field gradient (PFG) technique,
      it is possible to determine the size distribution of emulsion droplets. This
      method is extended so that the same measurements can be performed in the presence
      of flow. The resultant flow-compensating NMR-PFG technique is used to determine
      the oil droplet-size distribution of an oil-in-water emulsion flowing in a narrow
      tube at various flow rates. Comparison with the nonflowing oil droplet-size
      distribution enables the effect of velocity shear on the oil droplet-size
      distribution to be quantified.

PMID- 11820833
TI  - Sample restriction using radiofrequency field selective pulses in high-resolution
      solid-state NMR.
AB  - In this article a method is suggested for restricting a sample (spatial
      localization) by preparing the magnetization with a phase-modulated
      radiofrequency pulse which inverts magnetization only over a very narrow range of
      radiofrequency field strengths. This is the most efficient method, in terms of
      sensitivity, of restricting the sample to improve rf homogeneity. The method is
      demonstrated by using it to improve the resolution obtained in a homonuclear
      dipolar decoupling experiment.

PMID- 11820835
TI  - Graphical analysis of the relative orientation of molecular alignment tensors for
      a protein dissolved in two different anisotropic media.
AB  - In order to determine precise three-dimensional structures of proteins by
      residual dipolar coupling constants as the major or even exclusive structural
      constraints, it is essential to use two anisotropic media. In doing so, a
      reliable and versatile method for estimating the relative orientation of the
      alignment tensors for the molecules dissolved in different anisotropic media is
      required. In this communication, we present a new graphical approach for this
      purpose, which does not require structural information of the target molecules.
      The correlation map for the two independent data sets of residual dipolar
      coupling constants, which can be obtained for the molecules in different
      anisotropic media, strongly depends on the relative orientation of the alignment
      tensors. We have simulated the correlation maps for all possible combinations of
      the Euler angles, which transform one alignment tensor to the other, and compared
      them to the experimental data sets reported for labeled human ubiquitin. This
      simple graphical method affords a useful starting point for the structural
      determinations using residual dipolar couplings.

PMID- 11820836
TI  - Scaling laws in NMR scattering via dipolar fields.
AB  - Breaking translational symmetry in magnetostatics imparts a scale dependence that
      is commonly investigated in physics (W. Warren et al., 1993, Science 262, 2005
      2008). An interesting and important example arises in nuclear magnetic resonance
      studies involving the dipolar mean field of adjacent nuclear spins where the
      scattering (transfer of spatial spin gratings) via intermolecular macroscopic
      fields carries a signature of the local spatial distribution of the spin density.
      For arbitrary geometry, the inverse problem of extracting this spin distribution
      from experiments is intractable. Here we point out a simple, universal crossover
      in the scaling behavior at the sample's characteristic length scale, xi, of the
      species fluctuations in the sample along the measurement direction. This behavior
      is observed experimentally in an oil-water emulsion, an important representation
      of complex, heterogeneous, soft matter.

PMID- 11820837
TI  - R1rho relaxation outside of the fast-exchange limit.
AB  - Chemical-exchange effects in NMR spectroscopy enable kinetic processes to be
      characterized at equilibrium in solution. Beginning with the Bloch-McConnell
      equations, new expressions are derived for the spin relaxation rate constant in
      the rotating frame, R1rho, for chemical exchange between two sites that have
      distinct magnetic environments and Larmor frequencies. The results are accurate
      provided that the spin relaxation decay is dominated by a single exponential
      damping constant and are applicable to a wider range of conditions than existing
      theoretical descriptions. The new expressions for R1rho will be particularly
      useful in analyzing experimental data when exchange is not fast and site
      populations are unequal.

PMID- 11820838
TI  - Molecular phylogeny of short-tailed shrews, Blarina (Insectivora: Soricidae).
AB  - Phylogenetic relationships among the three described species of short-tailed
      shrews (genus Blarina) were inferred based on mitochondrial DNA sequences of 16S
      rRNA (506 bp) and cytochrome b (1137 bp) from 38 specimens representing B.
      brevicauda, B. hylophaga, and B. carolinensis, from across their range in North
      America. Phylogenetic analyses of both data sets combined followed tests showing
      lack of incongruence between these fragments. Analysis of substitution patterns
      indicated saturation of transitions at third codon positions in cytochrome b when
      Blarina sequences were compared to those of Sorex and Cryptotis, used as
      outgroups. Maximum-likelihood and weighted parsimony supported the monophyly of
      the genus and placed B. hylophaga as its basal branch, sister to B. brevicauda +
      B. carolinensis. Phylogeographic analysis revealed a significant partition
      between eastern and western populations of B. carolinensis and B. brevicauda, on
      either side of the Mississippi basin. These results are discussed in relation to
      cytogenetic, morphological, and fossil data.

PMID- 11820839
TI  - Phylogenetic relationships among the species of the genus Testudo (Testudines:
      Testudinidae) inferred from mitochondrial 12S rRNA gene sequences.
AB  - To test phylogenetic relationships within the genus Testudo (Testudines:
      Testudinidae), we have sequenced a fragment of the mitochondrial (mt) 12S rRNA
      gene of 98 tortoise specimens belonging to the genera Testudo, Indotestudo, and
      Geochelone. Maximum likelihood and neighbor-joining methods identify two main
      clades of Mediterranean tortoises, one composed of the species Testudo graeca,
      Testudo marginata, and Testudo kleinmanni and a second of Testudo hermanni,
      Testudo horsfieldii, and Indotestudo elongata. The first clade, but not the
      second, was also supported by maximum parsimony analysis. Together with the genus
      Geochelone, a star-like radiation of these clades was suggested, as a sister
      group relationship between the two Testudo clades could not be confirmed. The
      intraspecies genetic variation was examined by sequencing the mt 12S rRNA
      fragment from 28 specimens of T. graeca and 49 specimens of T. hermanni from
      various geographic locations. Haplotype diversity was found to be significantly
      larger in T. graeca compared with T. hermanni, suggestive of reduced genetic
      diversity in the latter species, perhaps due to Pleistocene glaciations affecting
      northern and middle Europe or other sources of lineage reduction. No ancient mt
      12S rRNA gene haplotypes were identified in T. graeca and/or T. hermanni
      originating from islands in the Mediterranean Sea, suggesting that these islands
      harbor tortoise populations introduced from the European and African mainland.

PMID- 11820840
TI  - Complete mitochondrial DNA of the hagfish, Eptatretus burgeri: the comparative
      analysis of mitochondrial DNA sequences strongly supports the cyclostome
      monophyly.
AB  - The phylogenetic position of cyclostomes, i.e., the relationships between
      hagfishes, lampreys, and jawed vertebrates is an unresolved problem. Anatomical
      data support the paraphyly of cyclostomes, whereas nuclear genes data support
      monophyly of cyclostomes. Previous results obtained using mitochondrial DNA are
      ambiguous, presumably due to a lack of informative sequences. By adding the
      complete mtDNA of a hagfish, Eptatretus burgeri, we have generated a novel data
      set for sequences of hagfishes and of lampreys. The addition of this mtDNA
      sequence to the 12 taxa we have already used becomes sufficient to obtain
      unambiguous results. This data set, which includes sequences of mtDNA of animals
      closely related to the lamprey/hagfish node, was used in a phylogenetic analysis
      with two independent statistical approaches and unequivocally supported the
      monophyly of cyclostomes. Thus molecular data, i.e., our results and those
      obtained using nuclear genes, conclude that hagfishes and lampreys form a clade.

PMID- 11820841
TI  - Gene diversity and geographic differentiation in mitochondrial DNA of the Genji
      firefly, Luciola cruciata (Coleoptera: Lampyridae).
AB  - The Genji firefly, Luciola cruciata, is divided into two ecological types, the
      fast-flash and slow-flash types, on the basis of the interflash interval of mate
      seeking males. To evaluate the evolutionary origin of the two types, 62
      populations were examined by restriction fragment length polymorphism analysis of
      the mitochondrial cytochrome oxidase (CO) II gene. As a result, 19 haplotypes
      were detected, and their distributions were indigenous to local areas.
      Phylogenetic trees constructed from sequence comparison of the haplotypes
      revealed three major clades (I, II, and III). The boundary of haplotypes between
      clades I and II is approximately concordant with the geological structure of the
      Japanese Islands, which is a great rupture zone called the Fossa Magna, and the
      distribution of haplotypes in clades III and I-II corresponds to the Kyushu and
      Honshu-Shikoku Islands, respectively. The results suggest a vicariant scenario in
      which current L. cruciata diversity would have arisen from phylogenetic
      separations subsequent to the formation process of the Japanese Islands based on
      the molecular clock. The CO II gene trees also suggested that the fast-flash type
      should be considered an ancestral form, while the slow-flash type would be a
      derived one. The divergence time between the slow- and the fast-flash types is
      estimated to be about 4.6 to 2.0 mya (the Pliocene epoch).

PMID- 11820842
TI  - A maximum-likelihood analysis of eight phylogenetic markers in gallwasps
      (Hymenoptera: Cynipidae): implications for insect phylogenetic studies.
AB  - We assessed the utility of eight DNA sequence markers (5.8S rDNA, 18S rDNA, 28S
      rDNA, ITS regions, long-wavelength opsin, elongation factor 1-alpha, cytochrome
      b, and cytochrome oxidase I) in reconstructing phylogenetic relationships at
      various levels of divergence in gallwasps (Hymenoptera: Cynipidae), using a set
      of eight exemplar taxa. We report sequence divergence values and saturation
      levels and compare phylogenetic results of these sequences analyzed both
      separately and combined to a well-corroborated morphological phylogeny.
      Likelihood ratio tests were used to find the best evolutionary model fitting each
      of the markers. The likelihood model best explaining the data is, for most loci,
      parameter rich, with strong A-T bias for mitochondrial loci and strong rate
      heterogeneity for the majority of loci. Our data suggest that 28S rDNA,
      elongation factor 1-alpha, and long-wavelength opsin may be potentially useful
      markers for the resolution of cynipid and other insect within-family-level
      divergences (circa 50-100 mya old), whereas mitochondrial loci and ITS regions
      are most useful for lower-level phylogenetics. In contrast, the 18S rDNA marker
      is likely to be useful for the resolution of above-family-level relationships.

PMID- 11820843
TI  - Molecular systematics of sciurognathi (rodentia): the mitochondrial cytochrome b
      and 12S rRNA genes support the Anomaluroidea (Pedetidae and Anomaluridae).
AB  - Nucleotide sequence data from the mitochondrial 12S rRNA and cytochrome b genes
      were used to analyze phylogenetic relationships among sciurognath rodents. Our
      sample taxa included representatives of 11 sciurognath and 3 hystricognath
      families with two marsupial species, Didelphis virginiana and Macropus robustus,
      as outgroups. The dataset was analyzed using both maximum-parsimony (weighted and
      unweighted) and likelihood methods. Three suprafamilial groupings are strongly
      supported: Geomyidae + Heteromyidae (Geomyoidea), Sciuridae + Aplodontidae
      (Sciuroidea), and Pedetidae + Anomaluridae (Anomaluroidea). Although moderately
      supported, two sister group relationships were identified between Gliridae and
      Sciuroidea and between Castor and Geomyoidea. In contrast to previous nuclear DNA
      evidence, the evolutionary affinities between Ctenodactylidae and Hystricognathi
      (Ctenohystrica) and between Muridae and Dipodidae (Myodonta) are not supported by
      the mitochondrial data. Molecular divergence dates based on the combined data
      were estimated for suprafamilial groupings and are discussed in the light of
      current morphological and paleontological interpretations of rodent phylogeny.

PMID- 11820844
TI  - Molecular phylogenetic relationships of neotropical salamanders of the genus
      Pseudoeurycea.
AB  - Pseudoeurycea, with 34 described species, is one of the most diversified groups
      of neotropical salamanders. I generated a phylogenetic hypothesis of
      relationships for Pseudoeurycea and related taxa, based on DNA sequences of 16S,
      Cyt b, and ND4 mitochondrial genes. The analyses include 27 species of
      Pseudoeurycea and samples from the monotypic Lineatriton, Ixalotriton, and
      Parvimolge. All phylogenetic analyses resulted in a paraphyletic Pseudoeurycea.
      Ixalotriton and Pseudoeurycea parva always form a monophyletic group. P. parva is
      transferred to Ixalotriton based on morphological and molecular grounds. The
      phylogenetic position of the newly defined Ixalotriton clade is uncertain since
      it is part of an unresolved basal polytomy. Parvimolge is closely related to
      Pseudoeurycea, and it is also part of the basal polytomy. Lineatriton, a highly
      specialized taxon, is deeply nested within Pseudoeurycea. In order to provide a
      taxonomic arrangement consistent with the monophyly of the different units that
      reflects both evolutionary history and morphological specialization,
      Pseudoeurycea should be split into several taxonomic units.

PMID- 11820845
TI  - A test of a mitochondrial gene-based phylogeny of woodpeckers (genus Picoides)
      using an independent nuclear gene, beta-fibrinogen intron 7.
AB  - A conservative estimate of the species tree for the woodpecker genus Picoides
      based on two mitochondrial protein-coding genes is tested using sequences of an
      independently evolving nuclear intron, beta-fibrinogen intron 7. The
      mitochondrial gene-based topology and the intron-based topology are concordant,
      and a partition-homogeneity statistical test did not detect phylogenetic
      heterogeneity. The intron evolves more slowly than the mitochondrial sequences
      and tends not to resolve relationships among recently evolved species. However,
      the intron is superior over mitochondrial genes in resolving older bifurcations
      in the phylogeny. The two data sets were combined resulting in a robust estimate
      of the Picoides species tree in which most every node is statistically supported
      by bootstrap proportions. The Picoides species tree clearly shows that many
      morphological and behavioral characters used to lump species into this single
      genus have evolved by convergent evolution. Picoides is considered the largest
      genus of woodpeckers, but the molecular-based species tree suggests that Picoides
      is actually a conglomerate of several smaller groups.

PMID- 11820846
TI  - Speciation in the globeflower fly Chiastocheta spp. (Diptera: Anthomyiidae) in
      relation to host plant species, biogeography, and morphology.
AB  - Phylogenetic relationships among the Chiastocheta species (Diptera, Anthomyiidae)
      were investigated using a 1320-bp mitochondrial DNA fragment including parts of
      cytochrome oxidase subunits I and II. Larvae of the Chiastocheta genus feed
      exclusively on Trollius (Ranunculaceae) seeds. Six Chiastocheta species (and two
      vicariant taxa) coexist on Trollius europaeus in Europe, where they were shown to
      be the sole pollinator of their host plant. In Asia, several Trollius species are
      parasitized by Chiastocheta spp., and several other Trollius species are free of
      Chiastocheta. The plant-insect association is thus obligate in Europe but
      facultative in Asia. This system therefore provides a unique opportunity to study
      the evolution of an obligate mutualism between a plant and its seed parasite
      pollinators and its consequences on insect diversification. Most parsimonious,
      distance, and maximum likelihood analyses of 16 haplotypes from Europe and 14
      from Asia show that European species do not form a monophyletic group. The
      species relationship indicated by egg morphology is only partly supported by
      molecular data. Moreover, a strong discrepancy between nucleotide variation and
      male genitalia morphology variation was found, particularly within and among
      European species coexisting on a single host plant. Molecular divergence across
      species ranges from 0 to 4.6%, suggesting a recent origin of the genus and
      several events of diversification, involving both host shifts and within-host
      plant radiation. We discuss alternative evolutionary scenarios that are
      consistent with molecular data.

PMID- 11820847
TI  - Optimization of polytomies: state set and parallel operations.
AB  - New algorithms for calculating the most parsimonious state sets for polytomies
      under Fitch parsimony are described. Because they are based on state set
      operations, these algorithms can be extended for optimization of several
      characters in parallel, thus increasing speed by a significant factor. This speed
      increase may facilitate analysis of molecular data sets, many of which contain
      hundreds of taxa, thousands of multistate nonadditive characters, and numerous
      polytomies.

PMID- 11820848
TI  - Molecular phylogeny and biogeography of the grass lizards genus Takydromus
      (Reptilia: Lacertidae) of East Asia.
AB  - Takydromus Daudin is a group of Lacertidae lizards with slender bodies and long
      tails. Half of the Takydromus spp. are endemic to islands of eastern Asia aligned
      along the Pacific margin of the East Asian continent. This feature offers a good
      opportunity to study the effects of glaciations and land connections on the
      speciation of East Asian fauna. We reconstructed the molecular phylogeny of
      Takydromus species via the mitochondrial 12S rRNA gene. Phylogenetic analyses
      using maximum-parsimony, neighbor-joining, and maximum-likelihood options do not
      support a two-subgenera scheme of Takydromus and Platyplacopus proposed earlier.
      In contrast, the phylogeny of Takydromus species on islands fits the sequential
      separation of island groups influenced by changes in sea level. The hypothesis in
      our prediction supports the process of vicariant speciation and multicolonization
      of grass lizards on eastern Asian islands. At least two obvious colonization
      events were followed by vicariance events. Because the molecular clock of the 12
      rRNA gene was not rejected in our model test, it is possible to estimate times of
      speciation events. As the most isolated and basal species compared to other
      temperate and subtropical species of Takydromus, the separation period of T.
      smaragdinus in the central Ryukyus is the crucial point in estimating the
      evolutionary rate. Quaternary-origin or Tertiary-origin models are proposed and
      discussed.

PMID- 11820849
TI  - Phylogeny and character evolution in the Empidonax group of tyrant flycatchers
      (Aves: Tyrannidae): a test of W. E. Lanyon's hypothesis using mtDNA sequences.
AB  - We sequenced mitochondrial DNA from four protein-coding genes for 26 taxa to test
      W. E. Lanyon's hypothesis of intergeneric relationships and character evolution
      in the Empidonax group of tyrant flycatchers. Three genera in this group
      (Empidonax, Contopus, and Sayornis) successfully occupy north temperate habitats
      for breeding, while the remaining genera (Mitrephanes, Cnemotriccus,
      Aphanotriccus, Lathrotriccus, and Xenotriccus) are restricted to neotropical
      latitudes. Lanyon hypothesized two major clades in the group based on differences
      in syringeal morphology and proposed relationships among genera using a
      combination of morphologic, behavioral, and allozymic characters. The mtDNA data
      strongly support Lanyon's division of genera into two clades. In addition, the
      molecular and nonmolecular data sets agree in uniting Aphanotriccus and
      Lathrotriccus as sister taxa, with Cnemotriccus as basal to these genera. Species
      of Aphanotriccus, Lathrotriccus, and Cnemotriccus form a clade that exploits a
      distinctive nesting niche relative to other members of the Empidonax group.
      Within the second major clade, mtDNA sequences support a reconstruction based on
      allozymes that places Contopus and Empidonax as sister taxa. This hypothesis
      contradicts that of Lanyon, who allied Contopus with Mitrephanes on the basis of
      similarity in foraging mode. Genera in the Empidonax group are members of a
      larger assemblage that radiated in South America. Occupancy of temperate habitats
      by certain genera in this group is coincident with their evolution of migratory
      behavior and with independent diversification in foraging modes that reduces
      potential competition in sympatry.

PMID- 11820850
TI  - Molecular phylogeny of hybridizing species from the genus Spartina Schreb.
      (Poaceae).
AB  - Interspecific hybridization events have been reported in the genus Spartina
      Schreb. (Poaceae), involving the east American species Spartina alterniflora, and
      including either introgression (e.g., with the western American Spartina foliosa)
      or allopolyploid speciation (e.g., with the Euro-African Spartina maritima).
      Molecular phylogenetic analysis of the genus has been undertaken in order to
      understand phylogenetic relationships and genetic divergence among these
      hybridizing species. Twelve Spartina species have been sequenced for two nuclear
      DNA regions (ITS of ribosomal DNA, and part of the Waxy gene) and one chloroplast
      DNA spacer (trnT-trnL). Separate and conditional combined phylogenetic analyses
      using Cynodon dactylon as the outgroup have been conducted. Spartina is composed
      of two lineages. The first clade includes all hexaploid species: the Euro-African
      S. maritima (2n = 60), the East-American S. alterniflora (2n = 62) and the West
      American S. foliosa (2n = 60). Spartina alterniflora appears as a closely related
      sister species to S. foliosa. Although belonging to the same lineage, Spartina
      maritima appears consistently more genetically differentiated from S.
      alterniflora than S. foliosa. The tetraploid species S. argentinensis (2n = 40)
      is placed at the base of this first clade according to the Waxy data, but its
      position is not well resolved by the other sequences. The second well-supported
      main lineage within genus Spartina includes the other tetraploid American
      species. Significant incongruence has been encountered between the waxy based
      tree and both the ITS and trnT-trnL trees concerning the position of S.
      densiflora, suggesting a possible reticulate evolution for this species. The
      results agree with hybridization patterns occurring in Spartina: introgression
      involving closely related species (S. alterniflora and S. foliosa) on one hand,
      and alloploid speciation involving more differentiated species (S. alterniflora
      and S. maritima) on the other hand.

PMID- 11820851
TI  - Phylogenetic relationships of North American garter snakes (Thamnophis) based on
      four mitochondrial genes: how much DNA sequence is enough?
AB  - The clade of garter snakes (Thamnophis) includes some of the most abundant and
      well-studied snakes in North America. However, phylogenetic relationships within
      this group have been little studied. We used DNA sequences of four mitochondrial
      genes (cytochrome b and NADH dehydrogenase subunits 1, 2, and 4) to estimate
      relationships among 29 of the 31 recognized species of Thamnophis plus the
      related species Adelophis foxi. Both maximum parsimony (MP) and maximum
      likelihood (ML) analyses of all these genes combined produced well-resolved trees
      with moderate (70-89%) to strong (90-100%) bootstrap support for most clades. MP
      and ML trees were very similar, with no strongly supported conflict between the
      two analyses. These analyses identify a clade of 12 species largely restricted to
      Mexico (the "Mexican clade"), and a clade containing 15 species that collectively
      range from Central America to southern Canada (the "widespread clade"). These two
      groups are identified as sister taxa in both MP and ML analyses. A clade
      consisting of the ribbon snakes (T. sauritus and T. proximus) and the common
      garter snake (T. sirtalis) is placed as the sister group to all other Thamnophis
      (i.e., the Mexican + widespread clades) in our analyses. High bootstrap
      proportions at several levels in the tree support the inclusion of both
      Thamnophis validus, which has traditionally been placed in the genus Nerodia, and
      the poorly known species Adelophis foxi within Thamnophis. We used randomly
      sampled characters (i.e., standard bootstrapping) and randomly sampled contiguous
      blocks of characters to examine the effect of number of characters on resolution
      of and support for relationships within Thamnophis using MP. In general, these
      analyses indicate that we have reached a point of strongly diminishing returns
      with respect to the effect of adding mtDNA sequence characters for the current
      set of taxa; our sample of 3809 mtDNA characters is apparently "enough." The next
      steps to improve the phylogenetic estimate may be to add nuclear DNA sequences,
      morphology, or behavior, or to sequence additional mtDNA lineages within species.

PMID- 11820852
TI  - Re: Phylogeny and taxonomy of marine mussels: comments on the paper by Distel
      (2000).

PMID- 11820853
TI  - Grapefruit juice potentiates the anti-inflammatory effects of diclofenac on the
      carrageenan-induced rat's paw oedema.
AB  - The anti-inflammatory effect of diclofenac alone or in combination with double
      strength grapefruit juice was investigated on carrageenan-induced rat's paw
      oedema. Paw was measured by using a plethysmometer 3 h after injecting the
      phlogestic agent. There was significant inhibition (P< 0.05) of the oedematous
      response after oral administration of diclofenac alone (1, 2.5, 5 mg kg(-1)p.o.)
      in a dose-dependent manner. Coadministration of grapefruit juice (10 ml kg(
      1)p.o.) orally with all doses of diclofenac, enhanced the inhibitory effect of
      diclofenac on rat's paw oedema. Double-strength grapefruit juice has synergistic
      inhibitory effect on rat's paw oedema when administered in combination with
      diclofenac.

PMID- 11820854
TI  - The effect of local administration of N-acetylcysteine in perforated rat tympanic
      membrane: an experimental study in myringosclerosis.
AB  - Myringosclerosis (MyS) is a common sequela of acute and chronic otitis media and
      ventilation tube treatment of serous otitis media. We aimed to study the effect
      of topical administration of N -acetylcysteine (NAC) on MyS by assessment of
      otomicroscopic evaluation, lipid peroxidation and nitric oxide (NO)
      (nitrite/nitrate) levels in experimental myringotomized rat tympanic membrane.
      Thirty adult rats were used and the upper posterior quadrant of the tympanic
      membranes of rats was myringotomized. Thereafter, they were divided into four
      groups. Group I received no treatment, group II was treated with saline, groups
      III and IV were treated with topical NAC (0.1 ml of 6 and 12 mg ml(-1),
      respectively). The levels of nitrite/nitrate and malondialdehyde (MDA) were
      measured in serum samples. In the otomicroscopic evaluation, non-treated and
      saline treated ears (controls) showed extensive occurrence of myringosclerotic
      plaques. Groups III and IV showed fewer occurrences of sclerotic plaques. There
      was no significant difference between groups III and IV regarding the development
      of MyS. The development of myringosclerotic lesion was found to be significantly
      different between NAC treated groups (III and IV) and the control groups (I and
      II). The levels of nitrite/nitrate of both groups III and IV were significantly
      lower than the control groups. The levels of MDA of these groups were also
      significantly lower than the control group. The relationship between groups III
      and IV was not statistically significant for the levels of nitrite/nitrate and
      MDA. We conclude that the topical treatment of NAC reduces the levels of MDA and
      NO products in rats. These results suggest that topical NAC application may be
      useful for the prevention of MyS.

PMID- 11820855
TI  - The influence of midazolam on plasma concentrations and pharmacokinetic
      parameters of lidocaine in rabbits.
AB  - The object of this study was to investigate the influence of midazolam on the
      plasma concentrations and pharmacokinetic parameters of lidocaine in rabbits.
      Lidocaine levels were determined by the immunofluorescence polarization method,
      using Abbott reagents. After intravenous administration of a combined dose of
      midazolam (0.2 mg kg(-1)i.v.) with lidocaine (1 mg kg(-1)i.v.) a statistically
      perceivable decrease of lidocaine concentration, together with an increase of the
      constant rate of its elimination and reduction of the biological half-life with
      average time of lidocaine remaining in the system were observed. Midazolam
      administered intravenously together with lidocaine shortens the residence time of
      the drug.

PMID- 11820856
TI  - Survey of oral hydrocortisone utilization in Madrid (Spain).
AB  - A progressive 69% increase in sales of hydrocortisone tablets was observed in
      Spain from 1988 to 1995. But there were no data suggesting an increase in the
      number of adrenal insufficiency cases. We aimed to assess the hydrocortisone
      prescription habits of physicians in 1996 in Madrid (Spain). An anonymous mail
      questionnaire was sent to 6130 randomly selected physicians (3345 generalists and
      2785 specialists) of Madrid. Five hundred and forty-six questionnaires (8.8%)
      were returned. Three hundred and eighteen physicians (58.2%) sometimes prescribed
      oral hydrocortisone. 70.8% of these physicians prescribed hydrocortisone for
      chronic adrenal insufficiency, 17.3% for acute adrenal insufficiency, 7.9% for
      congenital adrenal hyperplasia, and 30.2% for inflammatory diseases (asthma,
      allergic diseases, urticaria, rheumatic diseases, ulcerative colitis).
      Prescription for inflammatory diseases was more frequent in male physicians,
      physicians older than 40 years, and general practitioners. We can conclude that
      the main indication for hydrocortisone prescription was chronic adrenal
      insufficiency but there was a significant number of physicians that used the drug
      in inflammatory diseases. As a drastic increase in prevalence of adrenal
      insufficiency seems unlikely, the augmentation in sales of hydrocortisone could
      be explained by its prescription for other pathologies.

PMID- 11820857
TI  - The effect of osteogenic growth peptide (OGP) on proliferation and adhesion of
      HEMC-1 human endothelial cells.
AB  - Human osteogenic growth peptide (OGP) promotes the growth of osteoblastic,
      fibroblastic and bone marrow stromal cells. There is no evidence that OGP
      stimulates the growth or the attachment of endothelial cells to the extracellular
      matrix. The aim of this study was to test OGP on in vitro cultures of human
      microvascular endothelial HEMC-1 cells and to characterize its potential
      angiogenic effect when administered alone or in combination with vascular
      endothelial growth factor (VEGF) or its binding protein alpha(2)-macroglobulin
      (alpha(2)M). HEMC-1 cells were cultured in vitro under serum-free conditions to
      study the effects of OGP (10(-14)- 10(-10)M), VEGF (100 ng ml(-1)), alpha(2)M (20
      ng ml(-1)) and their combinations on cell proliferation for 48 h. Furthermore, an
      adhesion assay was performed incubating the HEMC-1 cells with OGP, VEGF,
      alpha(2)M and their combinations for 24 h. OGP, alpha(2)M and their combination
      did not stimulate proliferation of HEMC-1 cells; in contrast, VEGF caused a
      significant enhancement of cell growth ( +37.3 %;P< 0.05). Pre-incubation with
      VEGF resulted in a fast and increased adhesion of endothelial cells to the matrix
      as compared to controls ( +87.5 % at 30 min and +86.6 % at 70 min, P< 0.05); in
      contrast, incubation with OGP alone determined only a significant increase in the
      attachment at 100 min ( +52 %;P< 0.05). The combinations of these peptides did
      not cause significant additive effects. These results suggest that OGP, compared
      to VEGF, induced neither the proliferation nor an increase in attachment of HEMC
      1 cells to a matrix, either alone or in combination with VEGF and alpha(2)M.
      These in vitro findings may suggest a possible administration of OGP, as a
      haematopoietic factor, to patients affected by pathological conditions involving
      angiogenesis.

PMID- 11820858
TI  - Protective effects of dihydropyridine Ca-blockers against endothelial cell
      oxidative injury due to combined nitric oxide and superoxide.
AB  - Nitric oxide (NO) and superoxide anions (*O(2)(-) ), which are known to be
      generated by inflammatory cells under certain pathological conditions, may be
      cytotoxic to the endothelial cells (ECs) due to peroxynitrite formation. We
      reported previously that certain lipophilic dihydropyridine (DHP) Ca-blockers
      exhibit antioxidant activities. In the present study, the extent of antioxidant
      protection by nisoldipine against combined NO/*O(2)(-) or peroxynitrite-mediated
      EC injury was assessed and compared with nicardipine, nifedipine and Trolox
      (water-soluble vitamin E). When confluent bovine aortic ECs were exposed to
      combined NO/*O(2)(-) (generated from 0.25 mM SIN-1), dramatic loss of cell GSH
      (53 +/- 8%) occurred in 60 min; cell survival/viability, determined 24 h later by
      the tetrazolium MTT assay, decreased by 45 +/- 6%. NO alone or O(2)(-) alone were
      ineffective. Nisoldipine pretreatment (30 min) of the cells concentration
      dependently (0.3-10 micro M) attenuated the SIN-1-induced GSH loss: the
      EC(50)value was 4.7 micro M and the corresponding values for nicardipine and
      nifedipine were 7.8 micro M and >20 micro M, respectively, and that for Trolox
      was 5.2 micro M. These agents (10 micro M) also protected against the loss of
      cell viability: nisoldipine, 86 plus minus 8%; nicardipine, 60 +/- 7 %;
      nifedipine, 35 +/- 5 %, and Trolox, 78 +/- 9%. In addition, significant losses of
      GSH and viability could be induced by incubation of the EC monolayers with
      purified peroxynitrite (25 micro M). Attenuation of these peroxynitrite-mediated
      GSH and viability losses was observed with the following order of efficacy:
      nisoldipine > or = Trolox > nicardipine >> nifedipine. In a cell-free system
      containing 0.05 mM GSH, none of the agents (10 micro M) were able to inhibit SIN
      1- (0.25 mM) or peroxynitrite- (25 micro M) induced depletion (approximately 50%)
      of GSH. However, with a purified microsomal membrane system, all four agents
      inhibited the SIN-1- (or peroxynitrite-) induced lipid peroxidation (TBARS) with
      the following IC(50)values: nisoldipine, 6.3 micro M; nicardipine, 10.6 micro M;
      nifedipine, >20 micro M, and Trolox, 6.5 micro M. In conclusion, nisoldipine, a
      vascular selective DHP calcium channel-blocker, demonstrated the greatest
      protection against the EC injury induced either by SIN-1 or peroxynitrite. The
      protective mechanism against the cytotoxicity is most likely through a lipophilic
      'chain-breaking' antiperoxidative action against the 'OH-like species' released
      from peroxynitrite or SIN-1.

PMID- 11820860
TI  - The non-NMDA receptor antagonist NBQX does not affect rats performance in the
      object recognition task.
AB  - Though the AMPA receptor has been implicated in several neurodegenerative
      processes (epilepsy, ischemia, spasticity), its role in cognition is yet to be
      clarified. The aim of this study was to assess in the rat the effects of the AMPA
      receptor antagonist NBQX (3.5, 7, 10, 20 and 30 mgkg(-1), i.p.) on learning and
      memory. For this purpose, the object recognition task was chosen. NBQX, at the
      higher doses used (20 and 30 mgkg(-1)) caused respectively, depression of
      motility and ataxia, while given at lower doses (3.5, 7 and 10 mgkg(-1)) it did
      not influence animals performance in the object recognition paradigm. All rats
      acquired similarly well the task. In conclusion, these results would support and
      broaden previous observations on the lack of major involvement of AMPA receptors
      in the rat working memory mechanisms.

PMID- 11820859
TI  - Role of the cardiac Na(+)/H(+)exchanger in [Ca(2+)](i)and [Na(+)](i)handling
      during intracellular acidosis. Effect of cariporide (Hoe 642).
AB  - Intracellular acidosis is one of the alterations occurring in cardiac ischemia
      and has been discussed to be important in altering excitation--contraction
      coupling. The aim of this study was to determine how intracellular acidosis may
      affect intracellular sodium and calcium handling. Cardiomyocytes were isolated
      from the hearts of adult male guinea-pigs by standard techniques and superfused
      with modified Tyrode's solution at room temperature, either HEPES buffered
      containing 10 mM NaHCO(3)or HEPES buffered without NaHCO(3), in order to examine
      a possible interaction with the sodium bicarbonate symport. The whole cell
      voltage clamp technique was used utilizing 3 M Omega pipettes filled with (mM):
      Cs aspartate 120, CsCl 20, MgCl(2)1, NaCl 5, Mg-ATP 2, HEPES 10 and either 100
      microM Fura-2 or 100 microM SBFI. The pH of the pipette solution was either 7.2
      or 6.5. Cells were kept at a holding potential of -80 mV and after a pre-pulse to
      -40 mV the membrane was continuously clamped to potentials from -30 to +80 mV in
      10 mV steps. Intracellular Ca(2+)or Na(+)were estimated using the Fura-2 or SBFI
      technique (impermeable salt), respectively. The cardiac Na(+)/H(+)exchanger was
      inhibited using the Na(+)/H(+)- exchange inhibitor cariporide (Hoe 642) (1
      microM), when indicated. In NaHCO(3)-free experiments we found an increase in
      intracellular sodium reflected by a rise in the SBFI ratio of 0.326 +/- 0.01 upon
      intracellular acidification, in contrast to cells perfused at pH = 7.2 (no
      significant increase in intracellular Na(+)) (P< 0.05). There was no difference
      in intracellular calcium handling between cells perfused with solutions of pH =
      7.2 or 6.5 (Fura-2 Delta ratio: 0.79 +/- 0.10 vs 0.82 +/- 0.07, n.s.). The l 
      type calcium current also remained unchanged. Blockade of the Na(+)/H(+)exchanger
      by Hoe 642 had no influence on cells perfused at pH = 7.2 but inhibited the
      increase in intracellular Na(+)at pH = 6.5 (0.023 +/- 0.026 in the presence of
      Hoe 642 vs 0.326 +/- 0.01 without Hoe 642, P< 0.05) without affecting
      [Ca(2+)](i)or the L-type calcium current. In cells superfused with a Tyrode
      solution containing NaHCO(3), the increase in intracellular sodium concentration
      was even more pronounced. Under these conditions Hoe 642 also antagonized this
      increase in intracellular sodium but without reaching the control level. We
      conclude that under these experimental conditions intracellular acidification
      causes an increase in [Na(+)](i)without changing intracellular Ca(2+)or the L
      type calcium current. In addition in bicarbonate-buffered systems the acidosis
      induced increase in sodium is enhanced which may involve the Na(+)/HCO(3)(minus
      sign)symport. The effect of cariporide (Hoe 642) in intracellular acidosis seems
      to be based on antagonization of the rise in intracellular sodium rather than
      calcium in this model.

PMID- 11820862
TI  - Science information in the media: an academic approach to improve its intrinsic
      quality.
AB  - The lay audience expresses a clear demand for scientific information,
      particularly when health and welfare are involved. For most people science is
      what they learn from the media. The need for good scientific journalism is
      pressing, to bridge the gap between the slow pace of science and the fast-moving
      and concise nature of successful mass communication. This academic postgraduate
      course was established by the Department of Pharmacological Sciences to train
      mediators to improve the quality of lay scientific dissemination. The programme
      focuses on teaching a method of selecting, analysing, understanding, mediating
      and diffusing scientific information to lay people. The course explores the
      theoretical and practical aspects of methods, techniques and channels of
      scientific communication. Case studies, practical exercises, and stages
      complement the theoretical curriculum. The teaching focus is on reducing the
      asymmetry between scientists and the public. The different backgrounds of
      students and the spread of topics are major challenges.

PMID- 11820861
TI  - Alteration of biochemical parameters related with exposure to lead in heavy
      alcohol drinkers.
AB  - Blood lead levels (PbB), delta-ALA dehydratase activity (ALAD) and erythrocytic
      protoporphyrin (EPP) values were studied in heavy wine and spirit drinkers.
      Results were compared in both groups and with a control group (teetotalers).
      Results in all cases are expressed as arithmetic means +/- SD. PbB values found
      in the three groups were statistically different inter se: wine group, 195 +/- 82
      microg l(-1); spirits group, 159 +/- 69 microg l(-1); teetotalers, 72 +/- 43
      microg l(-1). ALAD was significantly lower in the drinker groups (wine 26.9 plus
      minus 11.4 U l(-1)and spirits 28.3 plus minus 11.6 U l(-1))vs the control group
      (48.3 plus minus 13.5 U l(-1)). Differences in EPP levels in the three groups
      were only significant between the teetotaler and the wine drinker groups. Our
      findings indicate that, in heavy drinkers (more than 2 liters of wine per day),
      not only are lead levels increased in the blood but there are also biochemical
      alterations that affect the heme biosynthetic pathway, which should be taken into
      account in treatment for alcoholics.

PMID- 11820863
TI  - Hepatoprotective activity of Achyrocline satureioides(Lam) D. C.
AB  - Aerial parts of Achyrocline satureioides(Lam) D. C. (Asteraceae) are used in folk
      medicine as infusions or decoctions for the management of several diseases
      including gastrointestinal and hepatic disorders. These data and the presence of
      flavonoids and caffeoyl derivatives have led us to study its hepatoprotective and
      choleretic activities. The hepatoprotective activity was evaluated in the
      bromobenzene- (BB-) induced hepatotoxicity model in mice through the measurement
      of the serum levels of alanine-aminotransferase (ALT) and aspartate transaminase
      (AST), thiobarbituric acid reacting substances (TBARS) and glutathione levels.
      The aqueous extract of the aerial parts of A. satureioides administered before
      BB, at the dose of 300 mg kg(-1)p.o., demonstrated significant inhibition (P<
      0.01) in the BB increase of liver ALT and AST and in the BB-induced increase of
      liver TBARS content. Also it was able to significantly increase (P< 0.05) the
      depleted levels of liver glutathione. In addition, at the same dose, a
      significant increase (P< 0.01) in the bile flow of rats was found. The results
      obtained with the aqueous extract of A. satureioides support its use in popular
      medicine as a hepatoprotective and digestive agent, and the effects might be
      mediated through the antioxidant and choleretic activities.

PMID- 11820864
TI  - Kolaviron modulates cellular redox status and impairment of membrane protein
      activities induced by potassium bromate (KBrO(3)) in rats.
AB  - In this study, we examined the modulatory effects of kolaviron, a biflavonoid
      from Garcinia kola seeds on the antioxidant defense mechanisms, cellular redox
      status and oxidative stress in the kidney and liver of rats pretreated with
      potassium bromate (KBrO(3)) intragastrically as a single dose of 300 mg kg(
      1)weight for 4 weeks. Treatment of rats with KBrO(3)resulted in an insignificant
      difference (P> 0.05) in body weight compared to controls. However, a significant
      increase in kidney/body weight ratio (P< 0.001) was observed in rats treated with
      KBrO(3)while liver/body weight ratio was not affected. KBrO(3)depressed the
      activities of superoxide dismutase, glutathione peroxidase and catalase (P<
      0.001) in the kidney but not in the liver. Kolaviron (200 mg kg(-1)body weight)
      administered three times a week for 4 weeks inhibited the decrease mediated by
      KBrO(3)of these enzymes in the kidney by 29, 88 and 45%, respectively. Similarly,
      kolaviron reduced the KBrO(3)-induced decrease in the activities of gamma 
      glutamyltransferase and microsomal Ca(2+)ATPase by 73 and 63% in the kidney. In
      addition, the extract elicited a 27 and 25% decrease in the KBrO(3)-induced
      increase in malondialdehyde and lipid hydroperoxide formation in the kidney.
      Kolaviron also attenuated the KBrO(3)-decreased activities of glucose 6
      phosphatase, 5 prime prime or minute nucleotidase and alkaline phosphatase
      (membrane enzymes) by 72, 57 and 25% respectively. The results of the present
      investigation indicate the antioxidative effect of kolaviron, a natural
      antioxidant, on drug-induced kidney toxicity. Kolaviron may therefore intervene
      in the cellular redox status and depression of membrane protein activities caused
      by KBrO(3)and other environmental carcinogens in the kidney.

PMID- 11820866
TI  - Porphyrin-oligothiophene-fullerene triads as an efficient intramolecular electron
      transfer system.
AB  - A series of porphyrin-oligothiophene-fullerene triads containing quaterthiophene,
      octithiophene, and dodecithiophene spacers has been synthesized. The fluorescence
      of the porphyrin chromophore in benzonitrile is efficiently quenched by electron
      transfer to the fullerene moiety. This process shows a weak distance dependence
      of the oligothiophene spacer with an attenuation factor beta= 0.11 A(-1).

PMID- 11820865
TI  - Increase of adenosine plasma levels after oral trimetazidine: a pharmacological
      preconditioning?
AB  - Trimetazidine (1-[2,3,4-trimethoxybenzyl] piperazine) (TMZ) is a cellular anti
      ischemic agent able to prevent intracellular ATP decrease, limit intracellular
      acidosis, protect against oxygen-free radical-induced toxicity and inhibit
      neutrophil infiltration. However, its definitive mechanism of action had not been
      identified. Recent studies showed the existence of an endogenous mechanism of
      cellular protection against ischemia, defined as 'ischemic preconditioning'. This
      mechanism was related mainly to cellular liberation of adenosine, a nucleoside
      with protective effects in myocardial ischemia. Since TMZ acts by increasing cell
      tolerance to ischemia and adenosine is the mediator of ischemic preconditioning,
      in this study we investigated a possible interaction between TMZ and adenosine.
      Two groups of patients affected by angina pectoris, were admitted to the study.
      They received a single oral dose of TMZ. One group was treated, during different
      sessions, with TMZ 10 and 20 mg, the other group with TMZ 40 and 80 mg. After a 3
      day wash-out from drug administration, each group received a placebo. Blood
      samples were collected at baseline (time 0) and 1, 2, 3, 4, 6, 8 h after drug
      administration, in order to detect plasma levels of adenosine by a high
      performance liquid chromatography method. We observed that the administration of
      TMZ at doses of 10, 20, 40 and 80 mg induced an increase of adenosine plasma
      levels of 19, 50, 62 and 62%, respectively. We hypothesized that the activity of
      TMZ could depend, at least in part, on adenosine mediation and this interaction
      opens a new interpretation of the drug antischemic effect.

PMID- 11820867
TI  - Redox refunctionalization of steroid spiroketals. Structure correction of
      ritterazine M.
AB  - The structure of the North spiroketal moiety of ritterazine M has been corrected
      from 1a to 1b. This was accomplished by comparison of published spectra of the
      natural product with five synthetic spiroketal-alcohols. Synthesis of these
      models was efficiently accomplished by reductive cleavage of the spiroketal and
      Sharpless asymmetric dihydroxylation of an isopentyl, methyl 1,1-disubstituted
      olefin, followed by Suarez iodine[III] oxidative spirocyclization of
      monoprotected 1 degree,3 degree 1,2 diols.

PMID- 11820868
TI  - The first total synthesis of (corrected) ritterazine M.
AB  - Hecogenin acetate was converted to ritterazine M in 16 operations with an average
      yield per opearation of 87%. The overall linear yield was 12%. This confirmed 1
      as the corrected structure for ritterazine M by total synthesis.

PMID- 11820869
TI  - Metal ligation regulates conformational equilibria and binding properties of
      cavitands.
AB  - A self-folding cavitand binds quinuclidinium cation in its vase conformation and
      lanthanum ions in its kite conformation. Metal coordination provides a novel
      switching mechanism for the uptake and release of guests.

PMID- 11820870
TI  - A novel method for the generation of nitrile oxides on solid phase: application
      to the synthesis of substituted benzopyranoisoxazoles.
AB  - A solid-phase synthesis of substituted benzopyranoisoxazoles is described. The
      six-step synthesis features a novel method of generating nitrile oxides on a
      polymer support followed by an intramolecular 1,3-dipolar cycloaddition with a
      tethered alkyne for assembly of the benzopyranoisoxazole scaffold. Furthermore,
      the utilization of single-bead attenuated total reflectance Fourier transform
      infrared (ATR-IR) microspectroscopy as an essential analytical tool for reaction
      optimization is highlighted.

PMID- 11820871
TI  - Selectivity in an encapsulated cycloaddition reaction.
AB  - A 1,3-dipolar cycloaddition takes place within a reversibly formed, self
      assembled capsule. The reaction proceeds through an unsymmetrically loaded
      encapsulation complex with absolute regioselectivity.

PMID- 11820873
TI  - Energy transfer processes in novel subphthalocyanine-fullerene ensembles.
AB  - A series of subphthalocyanine-C(60) dyads in which the two subunits are placed at
      different distances have been prepared and their electrochemical properties
      measured. Photophysical measurements reveal energy transfer events following the
      initial photoexcitation of the subphthalocyanine chromophore.

PMID- 11820872
TI  - Total synthesis of (+/-)fasicularin via a 2-amidoacrolein cycloaddition.
AB  - The total synthesis of the cytotoxin fasicularin is described. The key steps
      include the following: (1) an intermolecular Diels-Alder cycloaddition of a 2
      (triflamido)acrolein with the dioxolane ketal of trideca-1,3-dien-7-one to
      establish the trans-perhydroisoquinoline stereochemistry, (2) a
      stereoelectronically controlled hydride addition to a N(1)-C(2) iminium ion to
      introduce the equatorial hexyl substituent, and (3) elaboration of the pyrido
      ring by an internal aldol reaction.

PMID- 11820874
TI  - Self-organization of chalcogen-containing cyclic alkynes and alkenes to yield
      columnar structures.
AB  - Close contacts between chalcogen atoms in cyclic dienes and diynes are used to
      create columnar structures in the solid state. Rigid and fairly planar cycles
      with chalcogen centers are the preconditions for forming those columnar
      structures.

PMID- 11820875
TI  - Cerium(III) chloride promoted highly regioselective ring opening of epoxides and
      aziridines using NaN(3) in acetonitrile: a facile synthesis of 1,2-azidoalcohols
      and 1,2-azidoamines.
AB  - A convenient and efficient synthesis of 1,2-azidoalcohols and 1,2-azidoamines has
      been achieved by ring opening of epoxides and aziridines using cerium(III)
      chloride and sodium azide in acetonitrile. The reaction is highly regioselective
      and afforded the corresponding products in good to excellent yields under mild
      and neutral reaction conditions. The method is very rapid and equally compatible
      for both epoxides and aziridines.

PMID- 11820876
TI  - Alkali metal-mediated proline aggregation in solution observed by coldspray
      ionization mass spectrometry.
AB  - L-Proline aggregates to form cyclic clusters in the presence of alkali metal ions
      in solution, whereas a large-scale-aggregated chain structure was observed for
      several other amino acids. The major cyclic clusters are suggested to be
      constructed from trimeric and tetrameric subunits on the basis of direct solution
      analysis by coldspray ionization mass spectrometry.

PMID- 11820877
TI  - Highly effective, easily accessible screw-sense-determining end group in the
      asymmetric polymerization of 1,2-diisocyanobenzenes.
AB  - Enantiopure helical poly(quinoxaline-2,3-diyl) was formed stereoselectively in
      the polymerization of 1,2-diisocyanobenzene using a new organopalladium initiator
      bearing the (4S,5S)-N-acyl-4,5-dihydro-4,5-diphenyl-1H-imidazol-2-yl group as the
      polymer-end screw-sense-determinant.

PMID- 11820878
TI  - Molecular design and biological potential of galacto-type trehalose as a
      nonnatural ligand of shiga toxins.
AB  - Galacto-type trehalose, a "C-4 epimer of trehalose", possesses a stereochemical
      structure around the alpha(1-1)-linkage analogous to that of the globobiosyl
      alpha(1-4)-linkage in Gb(2) and Gb(3) ceramides, which are known as the ligands
      of Shiga toxins produced by pathogenic E. coli. This paper presents evidence
      supporting the new idea of using a trehalosyl alpha(1-1)-linkage as a substitute
      for the galactobiosyl alpha(1-4)-linkage.

PMID- 11820879
TI  - Efficient synthesis of 3-furanosyl-6'-furanosylphosphinate through a tandem
      sequential radical process.
AB  - The sodium salt of hypophosphorous acid is shown to act as a double radical
      precursor in a double, sequential radical addition on 3-exo-methylenefuranose
      derivative 14 and 4-ethylenefuranose 10 to furnish phosphinates 18d in good
      overall yields. Unambiguous structural assignment establishes the high
      diastereoselection of the process.

PMID- 11820880
TI  - Lewis acid promoted highly stereoselective rearrangement of 2,3-aziridino
      alcohols: a new efficient approach to beta-amino carbonyl compounds.
AB  - A new Lewis acid promoted rearrangement reaction of 2,3-aziridino alcohols was
      discovered, which involved the highly stereoselective construction of a
      diastereogenic quaternary carbon center and efficient formation of beta-amino
      carbonyl compounds in excellent yields. A wide variety of Lewis acids were proved
      to be effective for the reaction, and a possible reaction mechanism was also
      discussed.

PMID- 11820882
TI  - Microbial deracemization of alpha-substituted carboxylic acids.
AB  - An enzyme system of Nocardia diaphanozonaria JCM 3208 catalyzes the inversion of
      the chirality of various alpha-substituted carboxylic acids, such as 2
      phenylpropanoic acid and 2-phenoxypropanoic acid derivatives, via a novel
      deracemization reaction.

PMID- 11820881
TI  - The first total synthesis of (+/-)-arisugacin A, a potent, orally bioavailable
      inhibitor of acetylcholinesterase.
AB  - The first convergent total synthesis of (+/-)-arisugacin A was accomplished by
      stereoselective construction of the arisugacin skeleton via a Knoevenagel-type
      reaction of an alpha,beta-unsaturated aldehyde with a 4-hydroxy 2-pyrone and
      stereoselective dihydroxylation followed by deoxygenation.

PMID- 11820884
TI  - Light-induced decarboxylation of (o-acylphenyl)acetic acids.
AB  - Near-UV irradiation of both o-acetylphenyl- and o-benzoylphenylacetic acids in
      benzene solution results in their efficient decarboxylation. Their meta and para
      isomers do not undergo this process. The O-deuterated acids yield deuterated o
      acyltoluene products, suggesting the possibility of an intramolecular proton
      transfer step in the decarboxylation process, although intermolecular deuteration
      would achieve the same result. The corresponding esters and amides are
      essentially photoinert and, like the acids, do not undergo the benzocyclobutenol
      formation expected of o-alkylphenyl ketones.

PMID- 11820883
TI  - Synthesis of 5-pyridyl-2-furaldehydes via palladium-catalyzed cross-coupling with
      triorganozincates.
AB  - 5-Pyridyl- and 5-aryl-2-furaldehydes are prepared from furaldehyde diethyl acetal
      in a four-step, one-pot procedure:(i) deprotonation; (2) Li to Zn
      transmetalation; (3) Pd-mediated cross-coupling; (4) aldehyde deprotection.
      Triorganozincate 7 was found to transfer all three groups in the Pd-catalyzed
      cross-coupling reaction with haloaromatics.

PMID- 11820885
TI  - Unexpected remarkable stability of primary ozonides derived from alkenyl
      stannanes. One-pot synthesis of 1,2-diols from alkynes.
AB  - Primary ozonides derived from alkenyl stannanes display an unusual stability and
      can be transformed into 1,2-diols by treatment with dimethyl sulfide and borane
      methyl sulfide complex. This observation has been incorporated into the
      development of a novel one-pot strategy for the conversion of alkynes into 1,2
      diols.

PMID- 11820886
TI  - A catalyst that plays multiple roles: asymmetric synthesis of beta-substituted
      aspartic acid derivatives through a four-stage, one-pot procedure.
AB  - We report a new method for the catalytic, asymmetric synthesis of beta
      substituted aspartic acid derivatives in which the nucleophilic catalyst serves
      up to four discrete roles in a one-pot procedure: catalytic dehydrohalogenation
      of acid chlorides to form ketenes; catalytic dehydrohalogenation of alpha
      chloroamines to form the corresponding imines; catalyzed [2 + 2]-cycloaddition to
      produce intermediate acyl beta-lactams; and finally, nucleophilic ring opening to
      afford optically enriched beta-substituted aspartic acids in high
      enantioselectivity and diastereoselectivity.

PMID- 11820887
TI  - Total synthesis of siphonarin B and dihydrosiphonarin B.
AB  - The spirocyclic core of the siphonarins was constructed by a directed cyclization
      of a linear triketone, prepared using a Sn(II)-mediated aldol coupling and Swern
      oxidation at C9 and C13. To circumvent a facile retro-Claisen pathway generating
      a baconipyrone-type ester, a Ni(II)/ Cr(II)-mediated coupling reaction with vinyl
      iodide was used to complete the first synthesis of siphonarin B and
      dihydrosiphonarin B. A stable isomeric spiroacetal was also prepared which could
      not be equilibrated to the siphonarin skeleton.

PMID- 11820889
TI  - Predicting experimental complexation-induced changes in (1)H NMR chemical shift
      for complexes between zinc-porphyrins and amines using the ab initio/GIAO-HF
      methodology.
AB  - Ab initio calculations were carried out on zinc-porphyrins complexed to several
      amines: N-(3,5-dimethyl-pyridin-4-yl)-formamide, 1,4-diazabiciclo[2.2.2]octane
      (DABCO), and 1-azabiciclo[2.2.2]octane (quinuclidine). The proton chemical shifts
      of these complexes were calculated ab initio at the GIAO-HF/6-311G//HF/3-21G
      level of theory, and the obtained values agree satisfactorily with experimental
      results. The complexation-induced changes in (1)H NMR chemical shifts correlate
      well with differences in association constants of several host-guest complexes.

PMID- 11820888
TI  - Olefins turned alkylating agents: diastereoselective intramolecular Zr-catalyzed
      olefin alkylations.
AB  - The first examples of intramolecular Zr-catalyzed electrophilic alkylation of
      aryl olefins are disclosed. Substituted carbo- and heterocycles are prepared
      efficiently and diastereoselectively.

PMID- 11820890
TI  - Synthesis of phenylnitroxides bridged by an sp(3)-linkage.
AB  - Silicon- and carbon-bridged phenylnitroxides were synthesized. They exhibited
      similar ESR profiles independent of the nature of the sp(3) bridge and the
      substitution mode of the phenylene units. The spectra revealed a quintet signal
      at room temperature, which became a broad triplet by lowering the temperature.
      Accumulated ESR measurements at 77 K led to the successful observation of a
      signal at Deltam(s) = 2, indicating that the triplet state was involved in this
      system.

PMID- 11820891
TI  - Palladium(II)-catalyzed transfer vinylation of protected monosaccharides.
AB  - A method for the catalytic vinylation of protected monosaccharides bearing a
      single free hydroxyl function has been developed. Reaction of representative
      primary, secondary, and anomeric sugar hydroxyl functions with butyl vinyl ether
      as the reactant and solvent and (phen)Pd(OAc)(2) (phen = 1,10-phenanthroline
      ligand) as the catalyst gives the corresponding vinylated sugar products in 36
      79% yield. The catalyst requires the presence of traces of oxygen in the reaction
      mixture to prevent decomposition to Pd(0).

PMID- 11820892
TI  - Toward the creation of NMR databases in chiral solvents: bidentate chiral NMR
      solvents for assignment of the absolute configuration of acyclic secondary
      alcohols.
AB  - The absolute configuration of acyclic secondary alcohols can be established from
      analysis of the chemical shift behaviors of the adjacent carbons in bidentate
      chiral solvents (R,R)- and (S,S)-1d as formulated in the boxed illustration.

PMID- 11820894
TI  - Diastereoselective synthesis of protected syn 1,3-diols: preparation of the C16
      C24 portion of Dolabelides.
AB  - We have designed a new method to make synthons encompassing a protected syn 1,3
      diol motif and an aldehyde alpha to the 1,3-dioxane ring. An additional
      stereocenter was also created, potentially leading to stereochemically defined
      1,2,4-triols. This method was successfully applied to the synthesis of the C16
      C24 portion of Dolabelides.

PMID- 11820893
TI  - Synthesis of chimeric 7alpha-substituted estradiol derivatives linked to
      cholesterol and cholesterylamine.
AB  - We report the synthesis of 7alpha-substituted beta-estradiol derivatives bearing
      side chains terminated with cholesterol and 3beta-cholesterylamine. These
      chimeric compounds were designed to exhibit high affinity for estrogen receptors
      (ERs) and cellular plasma membranes to potentially enable regulated uptake of ERs
      by mammalian cells. Evaluation with recombinant yeast reporting compound-mediated
      ER dimerization revealed potencies similar to the antiestrogen ICI 182780.
      Compounds that efficiently deliver dominant negative ERs into cells may provide
      novel therapeutics against breast cancers.

PMID- 11820895
TI  - One-step synthesis of substituted 6-amino-5-cyanospiro-4-(piperidine-4')- 2H,4H
      dihydropyrazolo[3,4-b]pyrans.
AB  - Three-component condensation of 4-piperidinones (7), 5-pyrazolones (8), and
      malononitrile (4) proceeds chemically and electrochemically and is a convenient
      one-step means of synthesis of substituted 6-amino-5-cyanospiro-4-(piperidine-4')
      2H,4H-dihydropyrazolo[3,4-b]pyrans (12). The electrochemical reactions proceed
      under milder conditions and with yields 12-15% greater than those of the
      reactions catalyzed by chemical bases.

PMID- 11820896
TI  - Synthesis of cyclic sulfones by ring-closing metathesis.
AB  - A general and highly efficient synthesis of cyclic sulfones based on ring-closing
      metathesis has been developed. The synthetic utility of the resulting cyclic
      sulfones was demonstrated by their participation in stereoselective Diels-Alder
      reactions and transformation to cyclic dienes by the Ramberg-Backlund reaction.

PMID- 11820897
TI  - Surprises in the energetics of host-guest anion binding to calix[4]pyrrole.
AB  - Contrary to common expectation, calorimetric measurements do not corroborate the
      preference of calix[4]pyrrole for fluoride over chloride in acetonitrile
      solution.

PMID- 11820898
TI  - One-step synthesis of 3,5-disubstituted-2-pyridylpyrroles from the condensation
      of 1,3-diones and 2-(aminomethyl)pyridine.
AB  - 3,5-Disubstituted- and 3,4,5-trisubstituted-2-(2-pyridyl)pyrroles may be
      synthesized efficiently from the novel condensation of 2-(aminomethyl)pyridine
      and 1,3-diones. The cyclization reaction was found to proceed through the
      intermediacy of a (2-pyridyl)methylimine. A marked dependence of the
      regioselectivity in the reaction of unsymmetrical diones on the presence of
      additional aminomethylpyridine suggests that two pathways to the product pyrroles
      are available.

PMID- 11820900
TI  - Formal total synthesis of (+/-)-vindoline by tandem radical cyclization.
AB  - A formal total synthesis of (+/-)-vindoline 1 has been achieved featuring the
      tandem cyclization of radicals produced from the iodoaryl azide 19a.

PMID- 11820901
TI  - Synthesis of optically active alpha-aminoalkyl alpha'-halomethyl ketone: a cross
      Claisen condensation approach.
AB  - A simple and versatile method was developed for the synthesis of alpha-aminoalkyl
      alpha'-halomethyl ketone derivatives, which are useful intermediates of protease
      inhibitors. It involves selective halogenation of the alpha-position on a beta
      ketoester, which is prepared by cross-Claisen condensation using N-protected
      amino acid ester. The title compound is obtained in high yield after
      decarboxylation of the alpha-halo-beta-ketoester.

PMID- 11820899
TI  - An unexpected [1,5]-h shift in the synthesis of nitroanilines.
AB  - Addition of methyl acetoacetate to 2-nitrovinamidinium hexafluorophosphate salts
      leads to the formation of anilines or phenols in good to excellent yields
      depending on the alkylamine substituents. Small substituents, e.g., pyrrolidine,
      lead to the formation of anilines while large substituents, e.g., N,N
      diisopropyl, exclusively give phenols. Labeling studies implicate a [1,5]-H shift
      proceeding with excellent isotopic fidelity.

PMID- 11820902
TI  - A facile C-C bond cleavage in the epoxides and its use for the synthesis of
      oxygenated heterocycles by a ring expansion strategy.
AB  - The bicyclic epoxy alcohols when treated with DAST gave a new class of rearranged
      organofluorine compounds, by a ring expansion via C-C bond cleavage of the
      oxirane ring. The outcome of this reaction with respect to ring size and
      stereochemical relation between the functionalities is presented here.

PMID- 11820903
TI  - Facile palladium(0)-catalyzed ring expansion reactions of hydroxy methoxyallenyl
      cyclic compounds via hydropalladation.
AB  - Palladium(0)-catalyzed one-atom ring expansion of various hydroxy methoxyallenyl
      compounds has been achieved in excellent yields without the use of aryl halides.
      Hydroxy methoxyallenylisoindolinones, -indanones, and -phthalans have been
      readily converted to the corresponding isoquinolones, naphthoquinones, and
      isochromanones in the presence of P(o-tolyl)(3).

PMID- 11820904
TI  - The first intermolecular Friedel-Crafts acylation with beta-lactams.
AB  - The first intermolecular Friedel-Crafts acylation of a variety of aromatic
      substrates with azetidinones is described. The Friedel-Crafts acylations are
      performed under very mild conditions, using trifluoromethanesulfonic acid to
      produce beta-amino aromatic ketones in excellent yields.

PMID- 11820905
TI  - A modified Mannich-type reaction catalyzed by VO(acac)(2).
AB  - A facile VO(acac)(2)-catalyzed in situ generation of iminium ions from amine N
      oxides and their participation in a modified Mannich-type reaction is described.

PMID- 11820906
TI  - Dioxolane-to-bridged acetal-to-spiroketal via ring-closing metathesis and
      rearrangement: a novel route to 1,7-dioxaspiro[5.5]undecanes.
AB  - Several examples of 1,7-dioxaspiro[5.5]undecane spiroketal systems have been
      synthesized from the common bicyclic intermediate 1 via acid-catalyzed
      rearrangement. Intermolecular ketalization of C(2) symmetric diene diol 3 with
      ketone 9 and then desymmetrization by ring-closing metathesis rapidly constructs
      bicyclic acetal 1. The locked conformation and steric bias of 1 allow
      stereoselective functionalization of one or both double bonds before
      spiroketalization.

PMID- 11820908
TI  - Unlicensed and off-label drug use in children: implications for safety.
AB  - A significant number of children receive either an unlicensed or an off-label
      drug during their stay in hospital. Studies throughout Europe have shown that at
      least one-third of children in hospital and up to 90% of neonates in a neonatal
      intensive care unit receive such drug prescriptions. The medicines that are most
      frequently used off-label include analgesics, antibiotics and bronchodilators.
      The purpose of licensing a drug is to ensure safety, efficacy and quality. If a
      drug is used in a different manner, one would expect a greater risk of toxicity.
      Only three studies have commented on the risk of toxicity in relation to
      unlicensed or off-label drug use. Only one of these three studies prospectively
      tried to evaluate the risk associated with off-label and unlicensed drug
      prescription. This study suggested that the percentage of unlicensed and off
      label drug use was significantly associated with the risk of an adverse drug
      reaction. Two studies looking at adverse drug reactions suggest that there is a
      greater risk of a severe adverse drug reaction occurring in association with the
      off-label or unlicensed use of drugs. One study found that five out of eight
      severe adverse drug reactions were associated with the off-label use of a
      medicine. The other study found that 14 of 19 drug prescriptions associated with
      17 severe adverse drug reactions were either unlicensed or off-label. The risk of
      prescribing off-label and unlicensed drugs in children is not clear from the
      limited data available.

PMID- 11820909
TI  - Case-population studies in pharmacoepidemiology.
AB  - The case-population approach aims at providing a risk estimate by comparing the
      incidence of the disease of interest among those exposed to the drug under study
      with the incidence among the non-exposed. For that purpose, the cases with the
      disease of interest have to be ascertained independently of the exposure status.
      Their rate and pattern of exposure have to be ascertained by interview with a
      structured questionnaire. Information on the patterns and the prevalence of drug
      consumption is needed in order to estimate the rate of exposure, and drug
      consumption statistics can be used to this end. In this paper, we review the main
      characteristics of studies using this approach or a similar one, and studies
      where series of cases exposed to the drug of interest were compared with drug
      consumption statistics. We looked at selected basic methodological requirements.
      Most of the studies reviewed suffer from incomplete case ascertainment,
      inaccurate definition of the disease of interest, incomplete information on
      exposures and other risk factors, and/or limited control of potential
      confounding, among other limitations. All the reviewed studies had several
      limitations regarding the estimation of the population at risk. The methods used
      in case-population studies should be clearly described, particularly with respect
      to the identification of the cases (numerator) and the estimation of the
      consumption prevalence (denominator). Case-population studies can give
      approximate risk estimates, but the method should be validated by comparing its
      results with those of case-control studies.

PMID- 11820910
TI  - How do we best detect toxic effects of drugs taken during pregnancy? A EuroMap
      paper.
AB  - It is a major clinical and public health problem that there is no clear strategy
      as to how we best make use of information obtained when pregnant women take
      drugs. For this reason, some pregnant women are not treated as they should be and
      some are given drugs they should not use. We suggest a monitoring system that
      combines some of the available datasets in Europe. Using these sources as a
      starting point, one can develop a system that has sufficient power to detect even
      rare diseases like congenital malformations and sufficient diversity to detect
      several possible outcomes from spontaneous abortions to childhood disorders. We
      also suggest that case-crossover designs should be used in case-control
      monitoring systems that carry a high risk of recall bias. These considerations
      are based upon our results from a European Union-funded concerted action called
      EuroMaP (Medicine and Pregnancy).

PMID- 11820914
TI  - The North/South Ireland Food Consumption Survey. Introduction.

PMID- 11820915
TI  - Sampling description and procedures used to conduct the North/South Ireland Food
      Consumption Survey.
AB  - OBJECTIVE: The purpose of this survey was to establish a database of habitual
      food and drink consumption in a representative sample of Irish adults, aged 18-64
      years. The present paper describes the sampling protocol, response rate and
      characteristics of the survey population in terms of sex and age groups,
      seasonality, geographical location, marital status, social class, socio-economic
      status and education level. DESIGN: A cross-sectional food consumption survey was
      carried out. In the Republic of Ireland, a nationally representative sample of
      adults was randomly selected with a validated two-stage clustered design, using
      the electoral register as the sampling frame. This method produced a self
      weighting or 'epsem' sample of individuals, where each adult who was registered
      to vote had an equal opportunity of being selected. Similarly, in Northern
      Ireland, a two-stage random sampling procedure was used. The sampling frame was
      the electoral register, and the sample was stratified by urban/rural and by an
      index of material deprivation, to ensure representation of each sector of the
      community. The recruitment procedure was the same in the North and South. An
      introductory letter with an information leaflet was posted to each selected
      individual and these were followed up by a visit from a fieldworker, who invited
      participation in the survey. SETTING: Northern Ireland and Republic of Ireland
      between 1997 and 1999. RESULTS: The response rate, which is the percentage of the
      total number of people who completed a 7-day food diary (n=1379) out of the total
      eligible sample (n=2177), was 63%. Non-respondents and dropouts constituted 34%
      and 3%, respectively, of the total eligible sample. Compared with the most recent
      census figures available, the sample was generally found to be representative in
      terms of sex and age group profiles, geographical location, marital status,
      seasonality, social class, socio-economic group and education level. Data on sex
      and age group and geographical location were collected from non-respondents for
      comparison with the survey sample. There were no apparent differences between
      them. CONCLUSION: The North/South Ireland Food Consumption Survey has established
      a relational database of habitual food and drink consumption, in addition to data
      on habitual physical activity, anthropometric measurements, socio-demographic
      factors, lifestyle, health status indicators and attitudes, in a nationally
      representative sample of the population of the island of Ireland.

PMID- 11820916
TI  - The North/South Ireland Food Consumption Survey: survey design and methodology.
AB  - OBJECTIVE: The purpose of this survey was to establish a database of habitual
      food and drink consumption in a representative sample of Irish adults aged 18-64
      years. DESIGN: A cross-sectional food consumption survey was carried out. Food
      intake data were collected using a 7-day estimated food diary. Anthropometric
      data included measurements of weight, height, waist and hip circumferences and
      body composition using bioelectrical impedance analysis. Questionnaire data
      included assessments of health, lifestyle and socio-demographic status, levels of
      physical activity, attitudes to diet and health and restrained eating. SETTING:
      Northern Ireland and Republic of Ireland between 1997 and 1999. RESULTS: In
      total, 1379 adults aged 18-64 years participated in the survey and completed the
      7-day food diary. This paper gives details of the methods used to carry out the
      survey. Sampling, respondent recruitment, dietary assessment, collection of
      anthropometric and questionnaire data and data management and analysis are
      described. CONCLUSION: The North/South Ireland Food Consumption Survey is unique
      in being the first food consumption survey ever to be carried out in the Republic
      of Ireland and Northern Ireland concurrently using the same methodology.

PMID- 11820912
TI  - Benefits and risks of inhaled corticosteroids in chronic obstructive pulmonary
      disease.
AB  - Inhaled corticosteroids have a proven benefit in the management of asthma, but
      until recently, their efficacy in non-asthmatic, smoking-related chronic
      obstructive pulmonary disease (COPD) was not evidence-based. Airway inflammation
      in COPD differs from inflammation in asthma. Some studies have shown an effect of
      inhaled corticosteroids on airway inflammation in COPD but the clinical relevance
      of these results are unknown. Short-term studies evaluating the effect of inhaled
      corticosteroids in patients with COPD were associated with no or modest
      improvements in lung function. Data from five, long-term, large studies have
      provided evidence that prolonged treatment with inhaled corticosteroids does not
      modify the rate of decline of forced expiratory volume in one second (FEV(1)) in
      patients with COPD and no reversibility to short-acting beta(2)-adrenoceptor
      agonists. FEV(1) was slightly improved over the first 6 months of treatment in
      two studies and lower airway reactivity in response to methacholine challenge has
      been observed. Improvement of respiratory symptoms and health status was also
      reported in three studies. A reduction in the rate of exacerbations was observed
      in two studies. No survival benefit was demonstrated in any study. The advantage
      of using inhaled, rather than oral, corticosteroids is a reduction in adverse
      effects for the same therapeutic effect, because inhaled corticosteroids rely
      more on topical action than systemic activity. The long-term safety of inhaled
      corticosteroids is not known in patients with COPD. However, topical adverse
      effects, and systemic effects such as a decrease of bone density of lumbar spine
      and femur and cutaneous adverse effects, have been reported in patients with COPD
      after 3 years of treatment with inhaled corticosteroids.

PMID- 11820917
TI  - An evaluation of energy intakes and the ratio of energy intake to estimated basal
      metabolic rate (EI/BMRest) in the North/South Ireland Food Consumption Survey.
AB  - OBJECTIVE: To examine energy intakes (EI), their ratio to estimated basal
      metabolic rate (BMR(est) and the contribution of food groups to energy intake in
      the North/South Ireland Food Consumption Survey. DESIGN AND SETTING: Random
      sample of adults from the populations of Northern Ireland and the Republic of
      Ireland. Food intake data were collected using a 7-day food diary. Body weight
      and height were measured and EI/BMR(est) was calculated from reported energy
      intake and estimated basal metabolic rate. Dieting practices were assessed as
      part of a self-administered questionnaire. RESULTS: Mean energy intake in men was
      11.0 MJ and in women was 7.6 MJ, which is comparable to reported energy intakes
      in Northern Ireland and the Republic of Ireland over a decade ago. Mean
      EI/BMR(est) was 1.38. This increased to 1.42 after the exclusion of dieters and
      those who were unwell, but still remained less than the established cut-off of
      1.53. EI/BMR(est) was significantly (P<0.05) higher in men than in women and
      decreased significantly (P<0.05) with increasing BMI in both sexes. The four food
      groups that contributed 50% of energy in men and women were meat and meat
      products, breads and rolls, potatoes and potato products, and biscuits, cakes,
      pastries and puddings. CONCLUSIONS: Energy intakes have not changed remarkably in
      Northern Ireland or the Republic of Ireland in the last 10 years, but the mean
      EI/BMR(est) of 1.38 suggests that energy underreporting occurred. EI/BMR(est) was
      lower in women and in the overweight/obese. Additional multivariate analysis of
      the data is needed to identify more clearly subgroups of the population reporting
      lower than expected energy intakes and to evaluate the effect of low energy
      reporting on the consumption of various foods and food groups.

PMID- 11820918
TI  - Macronutrient intakes and food sources in Irish adults: findings of the
      North/South Ireland Food Consumption Survey.
AB  - OBJECTIVE: To describe macronutrient intakes and food sources of the adult
      population in the Republic of Ireland and Northern Ireland and to assess
      adherence of this population to current dietary recommendations. DESIGN: A cross
      sectional food consumption survey collected food intake data using a 7-day food
      diary. SETTING: Northern Ireland and the Republic of Ireland between October 1997
      and October 1999. SUBJECTS: One thousand three hundred and seventy-nine adults
      aged 18-64 years (662 males and 717 females). RESULTS: Mean daily energy intakes
      in men were 11 MJ per day, 15.5% was derived from protein, 34.8% from fat, 43.5%
      from carbohydrate and 5.9% from alcohol. Corresponding figures for women were 7.6
      MJ per day, 15.6%, 35.6%, 45.1% and 3.5%. When alcohol energy was excluded the
      contribution of fat and carbohydrate to energy did not differ between men and
      women. When compared with existing dietary recommendations, 93% of men and 86% of
      women had protein intakes above the Population Reference Intake. Two approaches
      were used to assess adherence to the fat and carbohydrate dietary
      recommendations: (1) the proportion of individuals in the population attaining
      these dietary targets and (2) the proportion of the population that was included
      in a 'compliers' group which had a group mean equal to these dietary targets.
      Thirty-three per cent of men and 34% of women met the target of 35% of food
      energy from fat and 78% of men and 80% of women comprised the 'compliers' group
      having a group mean of 35% of food energy from fat. Twenty-three per cent of men
      and 27% of women met the target of 50% of food energy from carbohydrate and 56%
      of men and 62% of women made up the 'compliers' group. Meat and meat products
      were the main source of fat (23%) and protein (37%), and bread and rolls (25%)
      were the main source of carbohydrate. CONCLUSION: A reduction in dietary fat
      intake remains an important public health issue in the Republic of Ireland and
      Northern Ireland. An increase in carbohydrate intake and attention to the rise in
      alcohol intake is also warranted.

PMID- 11820919
TI  - The North/South Ireland Food Consumption Survey: the dietary fibre intake of
      Irish adults.
AB  - OBJECTIVE: Mean daily intakes of dietary fibre (DF, Southgate) and non-starch
      polysaccharide (NSP, Englyst) are estimated in a representative sample of adults
      aged 18-64 years in Ireland. The contribution of food groups to DF and NSP intake
      is reported and fibre intakes are compared with dietary recommendations and with
      intakes in some European countries. DESIGN: Food consumption was estimated using
      7-day food diaries for a representative sample (n=1379); 662 men, 717 women) of
      18-64 year old adults in the Republic of Ireland and Northern Ireland selected
      from the electoral register. DF and NSP intakes were estimated from tables of
      food composition. RESULTS: The mean daily intake of DF in the total sample was
      20.2 g (standard deviation (SD) 7.8) [23.2 g (SD 8.5) in men, 17.4 g (SD 5.9) in
      women] or 2.24 g MJ(-1) (SD 0.7) [2.16 g MJ(-1) (SD 0.7) in men, 2.33 g MJ(-1)
      (SD 0.7) in women]. Mean daily intake of NSP was 14.8 g (SD 6.2) [16.7 g (SD 6.8)
      in men, 13.0 g (SD 5.0) in women] or 1.65 g MJ(-1) (SD 0.6) [1.56 g MJ(-1) (SD
      0.6) in men, 1.74 g MJ(-1) (SD 0.6) in women]. The main food groups that
      contributed to mean daily intake of DF (NSP) in the sample were breads 31% (23%),
      potatoes 19% (23%), and vegetables 17% (19%). Absolute intakes of DF and NSP were
      higher (P<0.001) in men than women; however, women overall consumed more
      (P<0.001) fibre-dense diets than men. Women aged 18-35 years consumed less
      (P<0.01) DF and NSP (g) than women aged 36-64 years. Both men and women aged 18
      35 years consumed less (P<0.01) fibre-dense diets than men and women aged 36-64
      years. The NSP intake was below the nutritional goal of 18 g day(-1) in 77% of
      adults and below the minimum of the recommended range (12 g day(-1) in 37% of the
      total sample. Compliance (i.e. the maximum number of individuals whose collective
      mean daily intake corresponded to the population goal) with the (UK) population
      goal for an average intake of 18 g day(-1) NSP was achieved by a greater
      proportion of the population (63%) than compliance with the (German) dietary
      fibre recommendation of 30 g day(-1) (27%) or the (Nordic) recommendation of 3 g
      MJ(-1) day(-1) (33%). CONCLUSION: DF (NSP) intakes were lower than dietary
      recommendations in a substantial proportion of the population. This is likely to
      contribute to impaired bowel function and constipation, which in turn may
      contribute to increased risk of chronic gastrointestinal disease.

PMID- 11820920
TI  - The North/South Ireland Food Consumption Survey: vitamin intakes in 18-64-year
      old adults.
AB  - OBJECTIVE: To estimate vitamin intakes and assess the contribution of different
      food groups to vitamin intakes in adults aged 18-64 years in Ireland as estimated
      in the North/South Ireland Food Consumption Survey. Intakes are reported for
      retinol, carotene, total vitamin A, vitamin D, vitamin E, thiamin, riboflavin,
      pre-formed niacin, total niacin equivalents, vitamin B6, vitamin B12, folate,
      biotin, pantothenate and vitamin C. The adequacy of vitamin intakes in the
      population and the risk of occurrence of excessive vitamin intakes are also
      assessed. DESIGN: Food consumption was estimated using a 7-day food diary for a
      representative sample (n=1379; 662 men and 717 women) of 18-64-year-old adults in
      the Republic of Ireland and Northern Ireland selected randomly from the electoral
      register. Vitamin intakes were estimated using tables of food composition.
      RESULTS: In general, the percentage of the population with vitamin intakes below
      the average requirement (AR) was low. Mean daily intake of total vitamin A was
      below the AR in 20.2% and 16.6% of men and women, respectively, and mean daily
      intake of riboflavin was below the AR in 12.5% and 20.6% of men and women,
      respectively. Mean daily folate intakes were below the AR for folate in 11.2% and
      6.6% of women aged 18-35 years and 36-50 years, respectively. Only 2.2% of women
      aged 18-35 years and 5.2% of women aged 36-50 years achieved the recommended
      folate intake of 600 microg day(-1) for women of reproductive age for the
      prevention of neural tube defects. A high proportion of the population has a low
      dietary vitamin D intake and is largely dependent on sunlight exposure to
      maintain adequate vitamin D status. Except for pre-formed niacin, the 95th
      percentile intake of vitamins did not exceed the tolerable upper intake level
      (UL) for any group and was much less than the UL for most vitamins. Although
      20.8% of men and 6.3% of women exceeded the UL for pre-formed niacin (which is 35
      mg, based on nicotinic-acid-induced flushing), the large contribution of meat and
      fish to the intake of niacin (as nicotinamide) suggests that the risk of
      overexposure to nicotinic acid is much lower than this and is probably solely
      related to supplement use. A small proportion of men (4.0%) and women (1.2%) aged
      51-64 years had retinol intakes that exceeded the UL (3000 microg) and while the
      95th percentile intake of women in the 18-50 year age group was well below the
      UL, 1.5% of 18-35-year-old and 2.4% of 36-50-year-old women had mean daily
      retinol intakes above the UL. About 2.0% of women had intakes of vitamin B6 that
      exceeded the UL (25 mg). There were significant differences by age and sex in
      nutrient densities of vitamin intakes between men and women and between age
      groups, which may be explained by differences in consumption of particular food
      groups as well as different patterns of supplement use. CONCLUSION: Nutritional
      adequacy of the population for most vitamins was good. Folate intake in women of
      childbearing age is not meeting current recommendations for the prevention of
      neural tube defects. The public health significance of the relatively high
      proportion of men and women with inadequate intakes of vitamin A and riboflavin
      and with low dietary intakes of vitamin D is unclear and should be investigated
      further. With the possible exception of niacin (flushing) and vitamin B6
      (neuropathy), there appears to be little risk of the occurrence of adverse
      effects due to excessive consumption of vitamins in this population, based on
      current dietary practices.

PMID- 11820921
TI  - The North/South Ireland Food Consumption Survey: mineral intakes in 18-64-year
      old adults.
AB  - OBJECTIVE: To measure mineral intakes and the contribution of different food
      groups to mineral intakes in adults aged 18-64 years in Ireland. Intakes are
      reported for Ca, Mg, P, Fe, Cu and Zn. The adequacy of mineral intakes in the
      population and the risk of occurrence of excessive intakes are also assessed.
      DESIGN: Food consumption was estimated using a 7-day food diary for a
      representative sample (n=1379; 662 men, 717 women) of 18-64-year-old adults in
      the Republic of Ireland and Northern Ireland selected randomly from the electoral
      register. Mineral intakes (Ca, Mg, P, Fe, Cu and Zn) were estimated using tables
      of food composition. RESULTS: Mean nutrient density of intakes was higher for
      women than men for Ca and Fe and increased with age for all minerals, except Ca
      for men and Fe for women. Meat and meat products were the major contributor to
      mean daily intakes of Zn (38%), P (23%), Fe (18%), Cu (15%) and Mg (13%); dairy
      products (milk, yoghurt and cheese) to Ca (44%), P (22%), Zn (14%) and Mg (11%);
      bread and rolls to Fe (21%), Cu (18%), Ca and Mg (17%), Zn (13%) and P (12%);
      potatoes and potato products to Cu (16%), Mg (14%) and Fe (10%); and breakfast
      cereals to Fe (13%). In women of all ages nutritional supplements contributed
      7.6%, 4.4%, 3.6% and 2.2% of mean daily intake of Fe, Zn, Cu and Ca,
      respectively, while in men of all ages, nutritional supplements contributed 2.7%,
      2.3%, 1.7% and 0.6%, respectively, to mean daily intakes of Fe, Zn, Cu and Ca.
      Adequacy of minerals intakes in population groups was assessed using the average
      requirement (AR) as a cut-off value. A significant prevalence of intakes below
      the AR was observed for Ca, Fe, Cu and Zn but not P. A higher proportion of women
      than men had intakes below the AR for all minerals. Almost 50% of 18-50-year-old
      females had intakes below the AR for Fe, while 23%, 23% and 15% of women of all
      ages had intakes below the AR for Ca, Cu and Zn, respectively. For men of all
      ages, 11%, 8% and 13% had intakes below the AR for Ca, Cu and Zn, respectively.
      There appears to be little risk of excessive intake of Ca, Mg, P, Cu or Zn in any
      age/sex category. However, 2.9% of women of all ages had intakes above the
      tolerable upper intake level for Fe (45 mg) due to supplement use. CONCLUSION:
      Almost 50% of women aged 18-50 years had Fe intakes below the AR and relatively
      high proportions of women of all ages had intakes below the AR for Ca, Cu and Zn.
      With the possible exception of iron intake from supplements in women, there
      appears to be little risk of excessive intake of minerals in the adult
      population. Meat and meat products, dairy products (milk, cheese and yoghurt),
      bread and rolls, potatoes and potato products and breakfast cereals are important
      sources of minerals; nutritional supplements make only a small contribution to
      mineral intakes in the population as a whole but may contribute significantly to
      intakes among supplement users.

PMID- 11820911
TI  - Locally administered ocular corticosteroids: benefits and risks.
AB  - Corticosteroids, used prudently, are one of the most potent and effective
      modalities available in the treatment of ocular inflammation. However, they can
      produce a plethora of adverse ocular and systemic events. In order to optimise
      and target drug delivery, whilst minimising systemic adverse effects, a diverse
      range of local ophthalmic preparations and delivery techniques have been
      developed. Topical drops and ointments remain the primary methods for
      administration of ocular corticosteroids. However, ocular penetration of topical
      corticosteroid drops depends upon drug concentration, chemical formulation of
      corticosteroid, and composition of the vehicle, therefore, apparently small
      modifications in preparations can produce a more than 20-fold difference in
      intraocular drug concentration. Periocular injections of corticosteroids continue
      to have a useful, but limited, therapeutic role and longer acting, intraocular
      delayed-release devices are in early clinical studies. Although newer
      corticosteroids with lesser pressure elevating characteristics have been
      developed, corticosteroid-induced ocular hypertension and glaucoma continue to be
      significant risks of local and systemic administration. Posterior subcapsular
      cataract, observed following as little as 4 months topical corticosteroids use,
      is thought to be due to covalent binding of corticosteroid to lens protein with
      subsequent oxidation. Inappropriate use of topical corticosteroid in the presence
      of corneal infections also continues to be a cause of ocular morbidity. Other
      risks of locally administered ophthalmic corticosteroids include: tear-film
      instability, epithelial toxicity, crystalline keratopathy, decreased wound
      strength, orbital fat atrophy, ptosis, limitation of ocular movement, inadvertent
      intraocular injection, and reduction in endogenous cortisol. This extensive
      review assesses the therapeutic benefits of locally administered ocular
      corticosteroids in the context of the risks of adverse effects.

PMID- 11820922
TI  - The efficacy and safety of nutritional supplement use in a representative sample
      of adults in the North/South Ireland Food Consumption Survey.
AB  - OBJECTIVE: To describe the current use of nutritional supplements and their
      contribution to micronutrient intakes in a representative sample of Irish adults,
      to evaluate the impact of supplement use on the adequacy of micronutrient intakes
      and to assess the risk to supplement users of exceeding tolerable upper intake
      levels (UL). STUDY DESIGN AND SUBJECTS: Food intake data were collected in 1379
      (662 male and 717 female) randomly selected Irish adults aged 18 to 64 years
      using a 7-day food diary. The current use of nutritional supplements was assessed
      using a self-administered questionnaire and respondents entered each supplement
      as it was consumed into the food diary. RESULTS: Twenty-three per cent of
      respondents regularly used nutritional supplements. Twice as many women used
      supplements as men. The intakes of micronutrients were significantly higher
      (P<0.001) in supplement users than in non-users. Micronutrient intakes from food
      sources were similar in male users and non-users of supplements, but were
      significantly higher (P<0.01) in female users, by 3 to 13%, for Fe, Mg, Mn,
      vitamins C and E and niacin than in non-users. The percentage of female users
      between 18 and 50 years who had mean Fe intakes below the average requirement
      (AR) (10 mg) decreased from 50 to 25 when the contribution from supplements was
      included. The use of supplements reduced the percentage of men who had mean
      intakes below the AR for Zn from 19 to 13, for riboflavin from 14 to 6 and for
      vitamin A from 20 to 5, and reduced the percentage of women with intakes below
      the AR for Ca from 23 to 16 and for riboflavin from 23 to 14. Twenty-one women
      out of 80 aged between 18 and 50 years, who consumed supplemental folate,
      achieved the intake of 600 microg recommended to prevent neural tube defects.
      Twenty-two per cent of the women who took iron and 15% of the women who took
      vitamin B6 in supplemental form had mean daily intakes that exceeded that UL for
      these nutrients. Supplement users did not exceed the UL for the other
      micronutrients. CONCLUSIONS: Supplementation appears to be beneficial in
      promoting adequate intakes of some micronutrients, particularly Fe and folate in
      women aged 18-50 years and vitamin A in men. There appears to be little risk to
      supplement users of experiencing adverse side effects due to excessive intakes of
      micronutrients.

PMID- 11820924
TI  - Physical activity patterns in a nationally representative sample of adults in
      Ireland.
AB  - OBJECTIVE: To evaluate habitual levels of physical activity in a nationally
      representative sample of adults in Ireland. DESIGN: Cross-sectional survey using
      a self-administered questionnaire. Usual levels of work, recreational and
      household activities were evaluated in relation to anthropometric, demographic
      and socio-economic characteristics. The amount and intensity of all activities
      were quantified by assigning metabolic equivalents (METS) to each activity.
      SETTING: Republic of Ireland and Northern Ireland, 1997-1999. SUBJECTS: Random
      sample of 1379 adults aged 18-64 years. RESULTS: Men were approximately twice as
      active in work and recreational activity (139.7 +/- 83.9 METS) as women (68.5 +/-
      49.8 METS; P<0.001) but women were three times more active in household tasks
      (65.9 +/- 58.7 METS vs. 22.6 +/- 24.6 METS; P<0.001). Overall levels of physical
      activity declined with increasing age, particularly leisure activity in men. In
      women the decline in work activity was offset by spending more time in household
      pursuits. Twenty-five per cent of the subjects were extremely overweight (body
      mass index (BMI>28 kg m(-2)) or obese (BMI >30 kg m (-2)). Fewer obese subjects
      reported higher levels of work and leisure activities. However, a higher
      percentage of obese women reported participation in the higher levels of
      household activities. Participation rates in recreational activities were low.
      Walking was the most important leisure activity of both men (41%) and women
      (60%). In terms of hours per week spent in vigorous physical activity, men were
      more active than women, professional and skilled non-manual women were more
      active than women in other social classes, and younger subjects (aged 18-35
      years) were more active than older subjects. CONCLUSIONS: The holistic approach
      used in the assessment of physical activity in this study has revealed important
      and subtle differences in the activity patterns of men and women. Failure to
      fully characterise the respective activity patterns of men and women could lead
      to ill-informed public health policy aimed at promoting and sustaining lifetime
      habits of physical activity. The results suggest that simple population-focused
      programmes to promote physical activity are unlikely to offer the same chance of
      long-term success as more sensitive and individualised strategies.

PMID- 11820923
TI  - Analyses of the anthropometric data from the North/South Ireland Food Consumption
      Survey.
AB  - OBJECTIVE: To obtain measured anthropometric data for weight, height and other
      parameters not previously measured in the Irish population such as waist and hip
      circumferences and body composition. DESIGN: A cross-sectional survey. Weight,
      height, waist circumference, hip circumference and body composition were measured
      according to standard procedures. SETTING: Northern Ireland and the Republic of
      Ireland, 1997-1999. SUBJECTS: Random representative sample of 1379 adults aged 18
      64 years. RESULTS: With the exception of body fat, all anthropometric values were
      significantly higher for men than women (P<0.001). All measurements were
      significantly higher in the 36-50-year-old age group compared with 18-35 year
      olds. Height was the exception, which decreased significantly with age (P<0.05).
      Weight, height and body mass index (BMI) have increased in Ireland since last
      measured in 1988 and in 1990. Over the last decade, obesity has increased in men
      2.5 fold from 8% to 20% and in women by 1.25 fold from 13% to 16%. Significantly
      more women have a normal BMI than men (50.4% vs. 33.3%; P<0.05). Cut-off points
      for a high waist circumference and high waist-to-hip ratio identified 47% and 33%
      of the population, respectively, to be at an increased risk for cardiovascular
      disease. Social class did not have any significant effect on mean BMI. Location
      of residence influenced BMI but not in any consistent manner. Ex-smokers had a
      significantly higher BMI than non-smokers and smokers (P<0.05). CONCLUSIONS: A
      revision of current recommendations for combating obesity is warranted to improve
      the health of the Irish population. Further research is needed to identify the
      factors that have contributed to the dramatic increase in the prevalence of
      obesity in men over the last decade and have resulted in a higher prevalence of
      obesity in men than in women.

PMID- 11820925
TI  - Attitudes towards and beliefs about nutrition and health among a random sample of
      adults in the Republic of Ireland and Northern Ireland.
AB  - OBJECTIVES: For effective healthy eating promotion, it is necessary to understand
      the attitudes towards and beliefs about nutrition of the general public. The
      objective of this study was to provide data on attitudes towards eating a healthy
      diet and the perceived need to alter eating habits from a random sample of adults
      in the Republic of Ireland and in Northern Ireland, using a self-administered
      questionnaire. DESIGN: Cross-sectional survey using a self-administered
      attitudinal questionnaire on beliefs and attitudes to healthy eating. SETTING:
      The survey was carried out between October 1997 and October 1999 in the Republic
      of Ireland and in Northern Ireland. SUBJECTS: A randomly selected sample of 1256
      adults from the Republic of Ireland and Northern Ireland completed the
      attitudinal questionnaire. RESULTS: A majority of subjects (62%) perceived that
      they make conscious efforts to eat a healthy diet either most of the time or
      quite often, while just over half (52%) agreed that they do not need to make
      changes to their diet as it is healthy enough. Subjects most likely to make
      conscious efforts to try to eat a healthy diet were females, older subjects (51
      64 years) and those with the highest intakes of fruit and vegetables and lowest
      quartile of fat (% food energy). When self-assessed adequacy of fruit and
      vegetables was examined, two-thirds of the total sample felt they ate too little
      fruit while just one-third felt they ate too little vegetables. CONCLUSION:
      Results of the present study, in general, revealed good agreement between
      attitude and behaviour with respect to healthy eating. This suggests that people
      appear to be reasonably accurate at evaluating their own diet in terms of how
      healthy it is. In terms of the two food groups examined in this study, some
      optimistic bias was evident for vegetables but not for fruit. It may be useful
      therefore to assess attitudes and beliefs about healthy eating by way of
      examining attitudes to such food groups individually.

PMID- 11820926
TI  - The North/South Ireland Food Consumption Survey. Conclusion.

PMID- 11820927
TI  - A hydroxysteroid sulfotransferase, st2b2, is a skin cholesterol sulfotransferase
      in mice.
AB  - The mRNA of a sulfotransferase (St2b2) mediating cholesterol sulfation was
      detected in mouse skin. Recombinant St2b2 also mediated the sulfation of
      pregnenolone, 3beta-hydroxy-5-cholen-24-oic acid, and dehydroepiandrosterone.
      St2b2 protein was detected in skin cytosols on Western blotting. The addition of
      10 nM TPA to skin epidermal cells from newborn mice resulted in a twofold
      increase in cholesterol sulfation and concomitantly enhanced the St2b2 content
      after 40 h. Other candidate cholesterol sulfotransferases, St2a4 and St2a9, were
      not detected in skin by RT-PCR. These results indicate that St2b2 is a
      cholesterol sulfotransferase in mouse skin.

PMID- 11820928
TI  - Structure determination of the constitutive 20S proteasome from bovine liver at
      2.75 A resolution.
AB  - The crystal structure of the 20S proteasome from bovine liver was determined by
      the molecular replacement method using the structure of the 20S proteasome from
      the yeast Sacccharomyces cerevisiae. The initial phases were refined by density
      modification coupled with non-crystallographic symmetry averaging. The structural
      model was refined with the program CNS. The final R-factor and R(free) were 0.25
      and 0.29, respectively. The constitutive proteasome without any contamination by
      the immunoproteasome was identified in the crystal structure.

PMID- 11820929
TI  - Planarian cytochrome b(561): conservation of a six transmembrane structure and
      localization along the central and peripheral nervous system.
AB  - Cytochrome b(561) is a major transmembrane protein of catecholamine and
      neuropeptide secretory vesicles in the central and peripheral nervous systems of
      higher animals. We succeeded in cloning a full-length cDNA encoding planarian
      cytochrome b(561). The deduced amino acid sequence shows a very similar six
      transmembrane topology to those of cytochromes b(561) of higher vertebrates and
      contains both putative ascorbate- and monodehydro ascorbate-binding sites. Among
      the six totally-conserved His residues of cytochrome b(561) in higher
      vertebrates, one is substituted with an Asn residue, indicating that His88 and
      His161 of bovine cytochrome b(561) play roles as heme b ligands at the
      extravesicular side. Northern- and Western-blot analyses confirmed the expression
      of the mRNA and protein with the expected sizes in planarians. The distributions
      of the mRNA and apoprotein were analyzed by in situ hybridization and
      immunohistochemical staining, respectively, showing two morphologically distinct
      structures, a pair of ventral nerve cords and the cephalic ganglion cluster in
      the head region. The present results suggest that the usage of ascorbate to
      supply electron equivalents to neuroendocrine-specific copper-containing
      monooxygenases is likely to have originated in organisms with a very simple
      nervous system.

PMID- 11820930
TI  - Molecular characterization of a novel beta1,3-galactosyltransferase for capsular
      polysaccharide synthesis by Streptococcus agalactiae type Ib.
AB  - A group B streptococcus, Streptococcus agalactiae type Ib, produces a high
      molecular-weight polysaccharide consisting of the following pentasaccharide
      repeating unit: -->4)-[alpha-D-NeupNAc-(2-->3)-beta-D-Galp-(1-->3)-beta-D-GlcpNAc
      (1-->3)]-beta-D-Galp-(1-->4)-beta-D-Glcp-(1-->. The type-specific capsular
      polysaccharide (CP) synthesis (cps) genes of this strain were cloned and
      analyzed. A cloned 10-kb DNA fragment contained cpsIbE to L and neu (neuraminic
      acid synthesis gene) B. Comparison of the gene products with those of S.
      agalactiae type Ia, which has a similar but distinct CP, showed that the
      translation products of cpsIa and cpsIb genes exhibited very high homology except
      for those of cpsJ and K. In the type Ia strain, cpsIaJ encodes beta1,4
      galactosyltransferase, which catalyzes the transfer of galactose as the fourth
      monosaccharide of the sugar repeating unit. In the type Ib CP, this galactose
      forms a beta1,3-linkage to GlcNAc. The low homology between the type Ia and Ib
      CpsJs seems to reflect this difference. By enzymatic activity measurement, the
      cpsIbJ product was found to display beta1,3-galactosyltransferase activity.
      Furthermore, hydrophobic cluster analysis clarified the similarities and
      differences of the structures in N-terminal regions, including the DXD motif,
      between the galactosyltransferases.

PMID- 11820931
TI  - Significance of the four carboxyl terminal amino acid residues of bovine
      pancreatic ribonuclease A for structural folding.
AB  - The C-terminal amino acid residues of bovine pancreatic ribonuclease A (RNase A)
      form a core structure in the initial stage of the folding process that leads to
      the formation of the tertiary structure. In this paper, roles of the C-terminal
      four amino acids in the structure, function, and refolding were studied by use of
      recombinant mutant enzymes in which these residues were deleted or replaced.
      Purified mutant enzymes were analyzed for their secondary structure, thermal
      stability, and ability to regenerate from the denatured and reduced state. The C
      terminal deleted mutant enzymes showed lower hydrolytic activity for C>p and
      nearly identical CD spectra compared with the wild-type enzyme. The rate of
      recovery of activity was significantly different among the C-terminal deleted
      mutant enzymes when air oxidation was employed in the absence of GSH and GSSG:
      the rates decreased in the order of des-124-, des-(123-124)-, and des-(122-124)
      RNase A. It is noteworthy that the regeneration rates of mutant RNase A in the
      presence of GSH and GSSG were nearly the same. Des-(121-124)-RNase A failed to
      recover activity both in the presence and absence of glutathione, due to the
      mismatched formation of disulfide bonds. The mutant enzyme in which all of the C
      terminal four amino acid residues were replaced by alanine residues showed lower
      hydrolytic activity and an indistinguishable CD spectrum compared with the wild
      type enzyme, and also recovered its activity from the denatured and reduced state
      by air oxidation. The D121 mutant enzymes showed decreased hydrolytic activity
      and identical CD spectra compared with the wild type. The recovery rates of
      activity of D121A and D121K were determined to be lower than that of the wild
      type enzyme, while the rate of recovery of D121E was comparable to that of the
      wild type. The C-terminal amino acids play a significant role in the formation of
      the correct disulfide bonds during the refolding process, and the interaction of
      amino acid residues and the existence of the main chain around the C-terminal
      region are both important for achieving the efficient packing of the RNase A
      molecule.

PMID- 11820932
TI  - Kinetic studies of novel di- and tri-propionate substrates for the chicken red
      blood cell enzyme coproporphyrinogen oxidase.
AB  - Coproporphyrinogen oxidase is an important enzyme in heme biosynthesis and
      catalyses the sequential oxidative decarboxylation of propionates on the A and B
      rings of the porphyrinogen ring. The effects of substituents on the C and D rings
      have not been systematically evaluated for their effects on the kinetic
      constants, K(m) and V(max). A series of synthetic porphyrinogens have been tested
      for their ability to affect these kinetic constants for the chicken enzyme. The
      enzyme exhibited the largest V(max) when incubated with the authentic substrate
      and was clearly able to distinguish between various substituents on the C and D
      rings of the macrocycle. When co-incubated with substrate, the authentic product,
      protoporphyrinogen-IX, appears to inhibit coproporphyrinogen oxidase and this may
      have an important role in the regulation of this enzyme. Thus the model for the
      active site of this enzyme should be modified to take these factors into account.

PMID- 11820933
TI  - Phospholipase C-gamma1 is required for survival in heat stress: involvement of
      protein kinase C-dependent Bcl-2 phosphorylation.
AB  - The consequences of heat-induced phospholipase C-gamma1 (PLC-gamma1)
      phosphorylation are not known. We investigated the role of PLC-gamma1 activation
      and its downstream targets during the cellular response to heat stress using
      mouse embryonic fibroblasts genetically deficient in PLC-gamma1 (Plcg1 null MEF)
      and its wild type (wt MEF) as models. Treatment of wt MEF with heat resulted in
      temperature- and heating duration-dependent tyrosine phosphorylation of PLC
      gamma1. HSP70 synthesis and the activation of extracellular signal-regulated
      kinases 1/2 (ERK1/2) and c-Jun N-terminal protein kinase (JNK) increased equally
      following heat treatment in both cell lines. However, heat-induced protein kinase
      C (PKC) activation was dramatically reduced in Plcg1 null MEF compared with wt
      MEF. Importantly, the mitochondrial localization of PKCalpha, PKC-dependent
      phosphorylation of Bcl-2, and cell viability in Plcg1 null MEF following heat
      treatment, were significantly decreased compared with the wild type. Furthermore,
      pretreatment with bryostatin-1, a PKC activator, enhanced Bcl-2 phosphorylation
      and cellular resistance to heat-induced apoptosis in Plcg1 null MEF. Taken
      together, these results suggest that PLC-gamma1 activation enhances cell survival
      through the PKC-dependent phosphorylation of Bcl-2 during the cellular response
      to heat stress.

PMID- 11820934
TI  - Contribution of an imidazole-indole stack to high catalytic potency of a lysine
      specific serine protease, Achromobacter protease I.
AB  - Achromobacter protease I (API), a lysine-specific serine-protease of the trypsin
      family, has an aromatic-ring stacking Trp 169-His 210 in close proximity to the
      reactive site. In order to investigate the role of this novel aromatic stacking,
      several mutants of the two residues were constructed and their kinetic parameters
      were determined. Three His 210 mutants showed lower activity by one order of
      magnitude than the wild-type with a peptide substrate of Ala-Ala-Lys-MCA (4
      methylcoumaryl-7-amide), but 30-170% activity towards Val-Leu-Lys-MCA, suggesting
      that His 210 plays a role in keeping high activity toward various substrates by
      maintaining the active form of the substrate-binding subsite. Kinetic results of
      eight Trp 169 variants showed a roughly linear relation between k(cat) or K(m)
      values and the surface area at residue 169. With increasing size of the side
      chain, k(cat) values increased, while K(m) values decreased. A systematic kinetic
      analysis of the activities of Trp 169 mutants toward Lys-MCA, Ala-Lys-MCA, and
      Ala-Ala-Lys-MCA peptide substrates revealed that large side-chain, rather than
      aromaticity, plays an important role in retaining the high catalytic activity of
      API. Due to the presence of the aromatic stacking, API shows one order of
      magnitude higher activity than bovine trypsin.

PMID- 11820935
TI  - Phospholipids promote dissociation of ADP from the Mycobacterium avium DnaA
      protein.
AB  - The biochemical aspects of the initiation of DNA replication in Mycobacterium
      avium are unknown. As a first step towards understanding this process, M. avium
      DnaA protein, the counterpart of Escherichia coli replication initiator protein,
      was overproduced in E. coli with an N-terminal histidine tag and purified to
      homogeneity on a nickel affinity column. The recombinant DnaA protein bound both
      ATP and ADP with high affinity and showed a weak ATPase activity. ADP, following
      the hydrolysis of ATP, remained bound to the protein strongly and the exchange of
      ATP for bound ADP was found to be weak. Acidic phospholipids such as
      phosphatidylinositol, phosphatidylglycerol, and cardiolipin, promoted the
      dissociation of ADP from the DnaA protein, whereas the neutral phospholipid,
      phosphatidylethanolamine, did not. The phospholipid promoted dissociation of ADP
      from DnaA protein was stimulated in the presence of the M. avium origin of
      replication. We suggest that the initiation of DNA replication in M. avium
      involves an interplay among DnaA, adenine nucleotides and phospholipids.

PMID- 11820936
TI  - Genomic clones encoding two isoforms of pokeweed antiviral protein in seeds (PAP
      S1 and S2) and the N-glycosidase activities of their recombinant proteins on
      ribosomes and DNA in comparison with other isoforms.
AB  - Pokeweed antiviral proteins (PAPs) are single-chain ribosome-inactivating
      proteins (RIPs) isolated from several organs of Phytolacca americana (Pokeweed)
      that are characterized by their ability to depurinate not only ribosomes but also
      various nucleic acids. PAP-S is one of the isoforms found in seeds. In this
      study, we obtained three different genomic clones encoding two forms of PAP-S
      (here designated as PAP-S1 and PAP-S2) and alpha-PAP after PCR using a pair of
      degenerated primers based on the known N- and C-terminal amino acid sequences of
      PAP-S. The nucleotide sequences of the genomic clones contained no introns. The
      deduced amino acid sequences of PAP-S1 and PAP-S2, which showed 83% identity to
      each other, were found to correspond to sequences reported independently for PAP
      S protein and cDNA, respectively, demonstrating that at least two forms of PAP-S
      actually exist in seeds of the same plant. The recombinant PAP-S1, PAP-S2, alpha
      PAP, and PAP I (a form appearing in spring leaves) exhibit the same level of
      depurinating activity on rat ribosomes, while their efficiencies on Escherichia
      coli ribosomes and salmon sperm DNA differ substantially from one another in the
      order of PAP I > alpha-PAP > PAP-S1 > PAP-S2 and alpha-PAP > PAP I > PAP-S1 > PAP
      S2. Structural comparisons suggest that the large difference in ribosome
      recognition between PAP-S1 (or S2) and PAP I is caused by the alteration of
      residues adjacent to the adenine-binding site.

PMID- 11820937
TI  - Cellular toxicity of cadmium ions and their detoxification by heavy metal
      specific plant peptides, phytochelatins, expressed in Mammalian cells.
AB  - The apoptotic cell death of Jurkat cells due to Cd(2+) toxicity was studied by
      fluorescence microscopic observation and DNA fragmentation assaying. It was
      suggested that the apoptotic response to Cd(2+) was less clear than that to a
      typical apoptosis inducer, ultraviolet light (254 nm). Examination of MAP kinase
      phosphorylation (p38, JNKs, and c-Jun) due to Cd(2+) toxicity indicated that the
      phosphorylation was very slowly activated (4 h after stimulation), while UV light
      could activate the phosphorylation immediately. Therefore, it was suggested that
      Cd(2+) may not be a typical apoptosis inducer. Antioxidants [glutathione (GSH)
      and N-acetylcysteine (NAC)] could detoxify Cd(2+), indicating that the toxicity
      is a kind of oxidative stress. The detoxification effect of antioxidants showed
      cooperation with Bcl-2, suggesting that Cd(2+)-treatment causes diversified toxic
      signals including oxidative stress. On the addition of a plant-specific peptide,
      phytochelatin [PC(7), (gammaGlu-Cys)(7)-Gly], to the medium, the detoxification
      of Cd(2+) and cooperation with Bcl-2 were more intense than in the cases of GSH
      and NAC. Using an appropriate vector, a PC synthase gene was transferred from
      Arabidopsis thaliana to the Jurkat cell. The transfectant exhibited resistance to
      Cd(2+) and production of plant-specific PC (PC(2-6)).

PMID- 11820938
TI  - Molecular cloning and expression of the mannose/glucose specific lectin from
      Castanea crenata cotyledons.
AB  - cDNA clones encoding a mannose/glucose specific lectin, CCA, from Castanea
      crenata cotyledons have been isolated and sequenced. The cloned CCA cDNA had an
      open reading frame of 927 bp encoding 309 amino acid residues. Compared with the
      amino acid sequence determined for the protein chemically, it was clarified that
      CCA has no signal peptide and undergoes no proteolytic cleavage as do other
      mannose specific Jacalin-related lectins. The coding region of CCA was introduced
      into an expression vector, pET-22b(+), and then transferred into Escherichia coli
      BL21(DE3). Although recombinant CCA (rCCA) accumulated as inclusion bodies,
      refolded rCCA exhibited a similar CD spectrum to nCCA and regained the
      hemagglutination activity. In addition, a hapten inhibition assay revealed that
      nCCA and rCCA showed the same specificities toward sugars and glycoproteins. On
      measurement by GPC-MALLS in the native state, the absolute molecular mass of nCCA
      was found to be 332 7 kDa, which indicated that nCCA is a decamer of identical
      subunits having a molecular mass of 33 kDa. The same as the natural molecule,
      rCCA showed a molecular mass of 320 +/- 5 kDa and was judged to also be a
      decamer. These results indicate that the rCCA obtained in this study is
      equivalent to nCCA.

PMID- 11820939
TI  - A new type of aminoacyltransferase from Saccharothrix sp. AS-2 favorable for the
      synthesis of D-amino acid-containing peptides.
AB  - A unique enzyme with some properties favorable for the synthesis of D-amino acid
      containing peptides has been purified from the culture broth of Saccharothrix sp.
      AS-2. The purification steps included ammonium sulfate fractionation,
      chromatographies on CM-Toyopearl 650M and ProtEx Butyl, and sucrose density
      gradient isoelectric focusing. The enzyme, consisting of four subunits of 56 kDa,
      showed its maximum transfer activity at around pH 8.2 and 35 degrees C, and had
      an isoelectric point of 5.8. The enzyme yielded homooligomers from methyl esters
      of D-Asp(OMe), D-Met, D-Phe, D-Trp, D-Tyr, and L-Glu(OMe), but showed no
      hydrolytic activity toward any of the D- or L-amino acid methyl esters tested.
      The homooligomers were not formed from the corresponding free amino acids. The
      reaction of Ac-D-Phe-OMe with DL-Ala-NH(2), DL-Leu-NH(2), DL-Phe-NH(2), or DL-Trp
      NH(2) was effectively catalyzed by the enzyme, both the DD- and DL-stereoisomers
      of the expected N-acetyldipeptide being yielded. The resulting dipeptides
      remained unhydrolyzed even after 48 h incubation. Also, it showed no detectable
      hydrolytic activity toward casein, diastereomers of diAla, diMet, and diPhe, D-/L
      amino acid amides, or D-/L-amino acid p-nitroanilides, indicating that the enzyme
      had no peptidase activity leading to secondary hydrolysis of the growing peptide.
      The enzyme activity was strongly depressed by phenylmethanesulfonyl fluoride, but
      not by penicillin G or ampicillin, suggesting that the protein is a serine enzyme
      lacking penicillin-binding ability. These observations lead us to the conclusion
      that the enzyme from Saccharothrix sp. AS-2 characterized in this study is a new
      type of aminoacyltransferase with an amino acid ester as the acyl donor, and has
      potential utility as a catalyst for the synthesis of D-amino acid-containing
      peptides.

PMID- 11820940
TI  - Quantification of galectin-7 and its localization in adult mouse tissues.
AB  - We developed a method to quantify galectin-7 extracted from adult mouse tissues
      by Western blot analysis. More than 0.5 ng of galectin-7 per mg of tissue was
      detectable by this method. The amounts of galectin-7 in tissues were determined
      as follows: skin, 62 +/- 3 ng/mg; esophagus, 23 +/- 8 ng/mg; stomach, 18 +/- 6
      ng/mg; anus, 13 +/- 1 ng/mg; and tongue, 12 +/- 2 ng/mg. This indicates that
      galectin-7 production coincides with the degree of stratification of the
      epithelia. Interestingly, we also detected significant amounts of galectin-7, 5.9
      plus minus 1.4 and 2.7 +/- 0.6 ng/mg, in the trachea and ovaries, respectively.
      Moreover, we found that galectin-7 is localized in the pseudostratified
      epithelium of the trachea and stromal epithelium of the ovaries by
      immunohistochemistry. Thus, galectin-7 protein might be produced primarily in
      stratified epithelia, but also in some wet epithelia, and plays a unique role in
      cell-mucus contact, or the growth of ovarian follicles.

PMID- 11820941
TI  - Sodium and sulfate ion transport in yeast vacuoles.
AB  - The intra-luminal acidic pH of endomembrane organelles is established by a proton
      pump, vacuolar H(+)-ATPase (V-ATPase), in combination with other ion
      transporter(s). The proton gradient (DeltapH) established in yeast vacuolar
      vesicles decreased and reached the lower value after the addition of alkaline
      cations including Na(+). As expected, the uptake of (22)Na(+) was coupled with
      DeltapH generated by V-ATPase. Disruption of NHX1 or NHA1, encoding known
      Na(+)/H(+) antiporters, did not result in the loss of (22)Na(+) uptake or the
      alkaline cation-dependent DeltapH decrease. Upon the addition of sulfate ions,
      the V-ATPase-dependent DeltapH in the vacuolar vesicles increased, but the
      membrane potential (DeltaPsi) decreased. Consistent with this observation,
      radioactive sulfate was transported into the vesicles with a K(m) value of 0.07
      mM. The transport activity was unaffected upon disruption of the putative genes
      coding for homologues of plasma membrane sulfate transporters. These results
      indicate that the vacuoles exhibit unique Na(+)/H(+) antiport and sulfate
      transport, which regulate the luminal pH and ion homeostasis in yeast.

PMID- 11820942
TI  - Real-time kinetic analyses of the interaction of ricin toxin A-chain with
      ribosomes prove a conformational change involved in complex formation.
AB  - Ricin toxin A-chain (RTA), a ribosome-inactivating protein from seeds of the
      castor bean plant (Ricinus communis), inactivates eukaryotic ribosomes by
      hydrolyzing the N-glycosidic bond of a single adenosine residue in a highly
      conserved loop of 28S rRNA, but does not act on prokaryotic ribosomes. We
      investigated the interaction of rat liver 80S ribosomes with RTA using an optical
      biosensor based on surface plasmon resonance (BIAcore instrument), which allows
      real-time recording of the interaction. RTA was coupled to the dextran gel matrix
      on the sensor chip surface through a single thiol group that is not involved in
      the enzymatic action. The interaction of rat ribosomes with RTA, which was
      greatly affected by the Mg(2+) concentration and ionic strength, was usually
      measured at 5 mM Mg(2+), 50 mM KCl, and pH 7.5. The modes of interaction of
      intact and RTA-depurinated rat liver ribosomes with the immobilized RTA were
      virtually the same, while no considerable interaction was observed for
      Escherichia coli ribosomes. The interaction was not influenced by the presence of
      5 mM adenine, which is higher than the reported dissociation constant (1 mM) for
      the adenine-RTA complex. These results demonstrate that binding of the target
      adenine with the active site of RTA does not contribute much to the total
      interaction of ribosomes and RTA. Global analyses of association and dissociation
      data with several binding models, taking account of mass transport, allowed us to
      conclude that the data were unable to fit a simple 1:1 binding model, but were
      best described by a model including a conformational change involved in high
      affinity complex formation.

PMID- 11820944
TI  - [The effects of inhaled bronchodilators on central inspiratory drive in patients
      with COPD].
AB  - OBJECTIVE: To evaluate the effects of inhaled bronchodilators on the central
      inspiratory drive in patients with COPD. METHODS: 91 patients with COPD were
      divided into three groups (A, B, C) randomly. Lung functions and P(0.1) were
      measured at baseline and 20 min and 60 min after inhalation (A: albuterol; B:
      iprotropium; C: albuterol + iprotropium). RESULTS: P(0.1) decreased after
      inhalation in all three groups (P < 0.05 approximately 0.001). A positive
      correlation between DeltaP(0.1) and DeltaFRC was found in the three groups (r =
      0.4325 - 0.5230, P < 0.05 approximately 0.01). V(E)/P(0.1) increased in the three
      groups after inhalation (P < 0.05 approximately 0.005). There was significant
      improvement of V(E)/P(0.1) in group B and C as compared with that of group A (P <
      0.05, P < 0.001); There was a different correlative factor with V(E)/P(0.1) in
      group B and C. CONCLUSIONS: (1) P(0.1) decreased after inhalation, It may be
      caused by decreased FRC. (2) V(E)/P(0.1) became appropriate after inhalation in
      all groups; The improvement in group B and C was superior to that of group A.
      There may be different mechanisms to improve V(E)/P(0.1) by different inhalators.

PMID- 11820945
TI  - [Mechanical ventilation of advanced chronic obstructive pulmonary disease
      patients with recurrent severe respiratory failure].
AB  - OBJECTIVE: To summarize the results of patients of severe respiratory failure
      using multiple times mechanical ventilation (MV) via tracheal intubation (or via
      tracheotomy). METHODS: We retrospectively analysed clinical information and
      follow-up results of 15 acute exacerbation of COPD patients using MV more than 3
      times. RESULTS: MV was used 77 times in 15 patients. The highest number of MV was
      20.86% were weaned successfully. The mean duration of MV via intubation was 13
      days and via tracheotomy was 37 days, mean 649 days via the latest brocheotomy
      after using MV multiple times. The survival duration after the first MV varied
      from 196 to 4 420 days in 15 patients, mean 1 093 days, medium survival duration
      of the patients was 1 673 days, survival rates after 1, 2, 3 and 5 years were
      73%, 64%, 33% and 25% respectively. The causes of death were failure of multiple
      organs or disfunction of other vital organs. CONCLUSIONS: Repeated application of
      MV may prolong the survival rates of COPD with severe respiratory failure. It's
      important to take strictly the indication of MV, correctly to select the methods
      of artificial airway, combining invasive and noninvasive ventilation, properly to
      apply the strategies of MV.

PMID- 11820943
TI  - Participation of two N-terminal residues in LPS-neutralizing activity of
      sarcotoxin IA.
AB  - Sarcotoxin IA is a cecropin-type antibacterial peptide of flesh fly. Using a
      mutant sarcotoxin IA lacking two N-terminal residues, we demonstrated that these
      residues are indispensable for its antibacterial activity against Escherichia
      coli and LPS-binding. Contrary to the native sarcotoxin IA, the mutant sarcotoxin
      IA could not neutralize various biological activities of LPS. It was suggested
      that sarcotoxin IA firmly binds to the lipid A core of LPS via these two N
      terminal residues and forms a stable binding complex that exhibits no appreciable
      biological activity like native LPS.

PMID- 11820946
TI  - [The tissue oxygenation status and the effects of mechanical ventilation on
      oxygen dynamics in COPD patients with hypercapnia].
AB  - OBJECTIVE: To assess the tissue oxygenation status and the effects of mechanical
      ventilation (MV) on oxygen dynamics in COPD patient with hypercapnia. METHODS:
      Gastric intramucosal pH (pHi) measured by gastric tonometer was examined in 19
      patients before and after MV. RESULTS: pHi calculated before MV was 7.18 +/-
      0.06; After receiving MV, pHi increased gradually until above 7.32 in 4 days;
      during weaning, there were no significant changes in pHi before and after
      discontinuation. The correlation analysis showed that there was no correlation
      between pHi and pHa (r = 0.352, P > 0.05), PgCO(2) and PaCO(2) (r = 0.421, P >
      0.05), suggesting that pHi measurement would not be affected by hypercapnia.
      CONCLUSIONS: Our study showed that tissue oxygenation insufficiency existed in
      COPD exacerbation stage. Gastric pHi may be used as the parameter to estimate
      tissue oxygenation status and a predictor of weaning from mechanical ventilation.

PMID- 11820947
TI  - [Investigation of factors affecting the development of COPD].
AB  - OBJECTIVE: To investigate the factors which affect the development of COPD.
      METHODS: 88 patients with mPAP less than 20 mm Hg were followed up by 5 - 20
      years. Pulmonary ventilation, blood gas analysis, ECG, pulmonary hemodynamic
      parameters and oxygen saturation at night were performed one time every 5 years.
      RESULTS: The results showed that: 5 year, 10 year and 20 year's mortality is 6%,
      25% and 43% respectively; MVV%, FEV(1)% and PaO(2) declined accompanied by the
      increase of PaCO(2); among 41 patients with mPAP 16 - 20 mm Hg, 20 patients' mPAP
      were more than 20 mm Hg and 15 patients died after 10 years' follow up. Among 16
      patients with the declination of oxygen saturation, 8 patients' mPAP were more
      than 20 mm Hg and 6 patients died. 57 strains of infectious bacteria were found
      in 88 patients' sputum with 43 strains in the death group. CONCLUSIONS: These
      results demonstrated that COPD is a kind of chronic diseases with high death
      rate; infection, decline of oxygen saturation at night and mPAP more than 16 mm
      Hg were high risk factors in COPD.

PMID- 11820948
TI  - [A clinical study of bacterial infection in patients with chronic obstructive
      pulmonary disease].
AB  - OBJECTIVE: To investigate the association of bacteriologic characteristics and
      bacterial infection in small airway disease. METHODS: Fiberoptic bronchoscopy and
      ultrathin fiberoptic bronchoscopy were performed on outpatients with COPD and
      chronic bronchitis both during stable stage and acute exacerbation. Samples were
      obtained from both large and small airways by protective specimen brush, and
      bacteria were cultured quantitatively. RESULTS: The positive rates for pathogens
      in patients with COPD and chronic bronchitis during acute exacerbation were 26.6%
      (8/30) and 23.5% (5/17) respectively. Major pathogens in acute COPD include
      Staphylococcus aureus, Streptococcus pneumoniae, Hemophilus influenzae, Moraxella
      catarrhalis, and Pseudomonas aeruginosa. All of the pathogens were present in
      large airways, with 2 strains present in small airways concurrently. The positive
      rates for pathogens in stable COPD and chronic bronchitis were 24.0% (6/24) and
      11.7% (2/17) respectively. Major pathogens found in stable COPD include
      Staphylococcus epidermis, Micrococcus and Streptococcus pneumoniae. The bacteria
      were less than 10 x 10(3) cfu/ml, present mainly in large airways. There was no
      significant difference in the extent of small airway diseases between COPD with
      bacterial infection and that without bacterial infection (P > 0.05). CONCLUSIONS:
      Bacterial infection is not a major pathogenic factor in stable COPD. There is no
      direct cause-and-effect relationship between bacterial infection and the extent
      of small airway diseases in patients with COPD.

PMID- 11820949
TI  - [The increased reactivity of isolated pulmonary artery rings from rats with
      hypoxia-induced pulmonary hypertension to activator of protein kinase C].
AB  - OBJECTIVE: To observe the reactivity of isolated pulmonary artery rings from rats
      with chronic hypoxic pulmonary hypertension (HPH) to protein kinase.C (PKC)
      activator. METHODS: Pulmonary artery rings from adult rats exposed to normobaric
      hypoxia for two weeks and normal rats were isolated for measurement of isometric
      contractions to PMA, the specific activator of PKC. Responses were examined as
      follows: (1) The maximal response (P(1)) to 0.5 micromol/L PMA and the time
      required to achieve a half-maximal response to 0.5 micromol/L PMA (t(1/2)); (2)
      Dose-response curve in response to PMA (0.01 - 10.0 micromol/L) and the dose of
      PMA that produced a contractile response as 50% of the maximal response (P(0)) to
      80 mmol/L KCl (EC(50) KCl). RESULTS: P(1) of hypoxic group (34.3 +/- 2.4) P(0)%
      was greater than that of normal group [(26.2 +/- 2.9) P(0)%, n = 6, P < 0.05)],
      t(1/2) and EC(50) KCl of hypoxic group [(27 +/- 7) min, and (0.7 +/- 0.1)
      micromol/L] were smaller than those of normal group [(32 +/- 5) min, n = 6, P <
      0.05, and (6.0 +/- 0.2) micromol/L, n = 12, P < 0.05]. CONCLUSIONS: The
      reactivity of pulmonary artery rings from hypoxic rats to PMA was enhanced, which
      indicates that protein kinase C may have an important role in the development of
      HPH.

PMID- 11820950
TI  - [The effect of inhaled ipratropium bromide on airway and lung tissue muscarinic
      receptors in a rat model of COPD].
AB  - OBJECTIVE: To observe the effect of inhaled ipratropium bromide on airway and
      lung tissue muscarinic receptors (MR) in a rat model of chronic obstructive
      pulmonary disease (COPD). METHODS: The rat model of COPD was established by
      chronic exposure with high concentrations of SO(2) gas, COPD rats inhaled
      aerosolized 0.025% ipratropium bromide solution 10 ml (twice/d, 20min/time). The
      MR was determined by radioligand binding studies with (3)H-QNB as the ligand.
      RESULTS: Compared with that of control, there was a marked increase in MR density
      on day 30 of treatment with ipratropium but not on day 5. The MR density
      decreased and close to normal level on the 6th day after cessation of regular
      therapy with inhaled ipratropium for 30 days. No significant difference was
      observed in antagonist affinity (Kd) among different time groups of ipratropium
      therapy. CONCLUSIONS: Chronic exposure to the anticholinergic agent ipratropium
      bromide produces an up-regulation of airway MR. The airway MR density can recover
      to normal when treatment stopped. Up-regulation of airway MR is associated with
      transient bronchoconstriction following cessation of regular ipratropium therapy
      and lung function deteriorated following long-term inhaled ipratropium bromide.

PMID- 11820951
TI  - [Effects of metalloproteinases on pulmonary fibrosis by bleomycin in rats].
AB  - OBJECTIVE: Matrix metalloproteinases (MMPs) are the mediators for dynamic
      equilibrium of extracellular matrix. The purpose was to investigate the effects
      of metalloproteinases on the development of pulmonary fibrosis. METHODS: The
      expression and activity of metalloproteinases of alveolar macrophage, and
      fibroblasts were evaluated on rats with pulmonary fibrosis induced by bleomycin.
      RESULTS: The activity of collagenase was low in the macrophage and fibroblast in
      control group, 20.4 x 10(-7) U/cell and 30.6 x 10(-7) U/cell respectively. There
      was an increase in the first and fourth week groups of bleomycin rats. The
      highest level of activity of alveolar macrophages was 258.0 x 10(-7) U/cell in
      first week group. A peak of enzymatic activity was found in 4th week group (289.0
      x 10(-7) U/cell). The mRNA of MMP-1, MMP-2 were expressed at lower levels in the
      normal lung tissue and there was an increase in first week, and fourth week group
      of bleomycin rats with a peak in one week group. CONCLUSIONS: The regulation of
      metalloproteinases might play an important role in the development of
      pathological processes in pulmonary fibrosis.

PMID- 11820952
TI  - [The effect of anti-transforming growth factor-beta1 antibody on fibroblast
      proliferation in vitro].
AB  - OBJECTIVE: Using anti-transforming growth factor-beta(1) antibody binding to
      transforming growth factor-beta(1) (TGF-beta(1)) in conditioned supernatant
      obtained from alveolar macrophages (AM) in broncho-alveolar lavage fluid (BALF)
      in bleomycin-induced rats, we investigated the effect of binding of TGF beta(1)
      to anti-TGF beta(1) antibody on proliferation and synthesis of collagen by
      fibroblast in pulmonary fibrosis. METHODS: Bleomycin (0.75 mg/100 BW) was
      instilled intratracheally into wistar rats, then broncho-alveolar lavage (BAL)
      was performed 7 days later. AMs (5 x 10(5)/ml) were cultured in 0.2% FCS RPMI
      1640 medium in vitro for 24 hours and conditioned medium was obtained. L929
      fibroblast (7 x 10(3)/well) was cultured in 96-well microtiter plate with
      conditioned medium and in different doses of anti- TGF beta(1) antibody (1, 5,
      10, 20 microg/ml) and IgG for 24 hours respectively. (3)H-Tdr was added 1 microCi
      per well for 6 hours before culture finished. The proliferation of fibroblast was
      studied by (3)H-Tdr incorporation rate and synthesis of collagen type IV was
      tested by ELISA. RESULTS: (1) Fibroblast proliferation which was induced by AM
      conditioned medium could be significantly depressed by anti-TGF beta(1) antibody
      in vitro (P < 0.01), and it appeared in a dose-dependent manner. (2) Synthesis of
      collagen type IV was depressed about 32% by 10 microg/ml anti-TGF beta(1)
      antibody. CONCLUSIONS: Fibroblast proliferation and collagen synthesis could be
      depressed by anti-TGF beta(1) antibody in vitro. It seems possible to provide a
      new way for the treatment of pulmonary fibrosis.

PMID- 11820953
TI  - [Gastric colonization and its effect on pathogenesis of nosocomial pneumonia].
AB  - OBJECTIVE: To study the gastric colonization and its effect on development of
      nosocomial pneumonia (NP). METHODS: We investigated the microorganism (mainly
      pathogens) constitution, isolating sequences and risk factors in gastric,
      oropharyngeal and lower respiratory tract flora. Microbiologic cultures of
      serially taken samples of gastric aspirates, oropharyngeal swabs and
      bronchoalveolar lavages (BALs) or sputums were performed at the time of ICU
      admission and subsequently every morning in 52 surgical patients with nasogastric
      tube. Etiologic diagnosis of NP was based on quantitative cultured of BAL or
      sputum. Sequences of colonization were examined by comparing isolates of the same
      species with concordance of minimum inhibitory concentration values to 12
      antibiotics. RESULTS: A total of 237 pairs of gastric and oropharyngeal specimens
      were taken. 77 strains of gram- negative bacilli (GNB) isolated from stomach,
      more than the number of GNB isolated from oropharynx (51 strains), P = 0.007.
      Comparing the species, Enterobacteriaceae isolated from stomach was much more
      than that from oropharynx (46 vs 24 strains, P = 0.004), and in most instances
      stomach colonization was before oropharynx colonization one to two days.
      Isolating rates of Pseudomonas were the same in both kinds of specimens. On
      contrast, Acinetobacter colonization in oropharynx was much more than that in
      stomach (10 vs 3 strains, P = 0.049). Risk factors for GNB colonization in
      stomach included increased gastric pH, medications inhibiting gastric acid
      secretion (such as cimitidine, omeprazole), and systemic use of cephalosporins.
      10 patients developed NP and 5GNB (Enterobacter cloacae 2, Pseudomonas aeruginosa
      2, Acinetobacter anitratum 1) isolated from BAL or sputum in 4 of 10 patients. A
      sequence of colonization from the stomach to the respiratory tract leading to
      pneumonia was observed in 3 patients. CONCLUSIONS: It was suggested that the
      stomach is likely to be an important source of pathogens leading to NP,
      especially Enterobacteriaceae pneumonia.

PMID- 11820955
TI  - [Delegated accreditation or delayed accreditation?].

PMID- 11820956
TI  - [Descriptive study of mental disorders in ethnic minorities residing in an urban
      area of Barcelona].
AB  - AIM: To observe the differences between ethnic groups and the autochthonous
      population in the frequency of mental disorders. To study epidemiological data
      and the accuracy of recording of such data. DESIGN: Descriptive study. Setting.
      Raval Sud Basic Health Care Area. Drassanes Primary Health Care Center,
      Barcelona, Spain. PATIENTS: A random sample of 112 immigrant patients belonging
      to ethnic minorities, seen between January 1995 and December 1997, matched for
      age and sex with autochthonous patients. Interventions. We studied variables
      related with mental disorders in immigrants. Variables included age, country of
      origin, reason for immigrating, employment status, marital status, other persons
      in household, educational level, knowledge of Spanish and toxic habits. We
      recorded the following impressions of diagnosis: anxiety, depression,
      somatization, psychosis, personality disorder, number of visits for each
      diagnosis, treatment, and overall number of visits between January 1995 and
      December 1997. Statistical studies consisted of descriptive analysis and chi
      squared tests. MEASURES AND RESULTS: Mean age was 39 14 years, 52.7% of the
      immigrant patients were men, 36.6% (95% CI, 27.6-45.5%) were from the Maghreb
      region, and 23.2% (95% CI, 15.4-31.0%) were Hindustani. 43% (95% CI, 33.6-52.0%)
      understood Spanish. Smoking was more frequent among autochthonous patients
      (59.8%; 95% CI, 50.7-68.9%) than in immigrant patients (26.8%; 95% CI, 18.5
      34.9%; p < 0.001), as was alcohol abuse (24.1%; 95% CI, 16.1-32.0%, versus 5.4%;
      95% CI, 1.1-9.5%; p < 0.001). Depression tended to be more frequent in patients
      belonging to ethnic groups (15.2%; 95% CI, 8.5-21.8%) than in autochthonous
      patients (13.4%; 95% CI, 7.0-19.7%; p = ns), as did somatization disorder (10.7%;
      95% CI, 4.9-167.4%, versus 6.3%; 95% CI, 1.7-10.7%, p = ns), but was undertreated
      (19.8%; 95% CI, 2.4-27.2%, versus 32.1%; 95% CI, 23.4-40.7%; p = ns). The total
      number of visits during the study period was higher in autochthonous patients
      (1138 versus 1017), as was the number of visits for mental disorders (17.9%; 95%
      CI, 15.7-20.1%, versus 13%; 95% CI, 1.9-15.0%; p = ns). CONCLUSIONS: There were
      no differences in the percentages of mental disorder

PMID- 11820957
TI  - [Mental disorders in ethnic minorities: is it a subject for research in primary
      care?].

PMID- 11820954
TI  - [A clinical study on vaccine of Mycobacterium vaccae in treating pulmonary
      tuberculosis].
AB  - OBJECTIVE: To study the effect of vaccine of Mycobacterium vaccae on cell
      mediated immunity and on treating patients with pulmonary tuberculosis. METHODS:
      Seventy cases of pulmonary tuberculosis with smear positive and initial treatment
      were classified randomly into group I (35 cases) and group II (35 cases),
      receiving 2HRZS/4HR and 2HRZS/4HR plus vaccine of Mycobacterium vaccae regimens
      respectively. Thirty-one multi-drug resistant pulmonary tuberculosis cases were
      classified into group III, receiving 4 - 6 sensitive antituberculous drugs and
      vaccine of Mycobacterium vaccae. Improvement of clinical symptoms, resolution of
      pulmonary lesions, negative conversion of sputum and changes of immunological
      functions were observed. RESULTS: No significant difference in improvement of
      symptoms was found in group I and group II (P > 0.05), and the improvement rate
      of clinical symptoms in group III was found more than 50%. X-ray resolution rates
      in 4th month were 83% and 89%, and cavity reducing rates 40% and 50% respectively
      in group I and group II, and no significant differences were found (P > 0.05). X
      ray resolution rate was 29%, cavity reducing rate 7% and no deteriorated case was
      found in group III. Sputum negative conversion rates in 1st, 2nd, 3rd and 4th
      month were 23%, 51%, 83% and 97% respectively in group I, while 31%, 77%, 89% and
      100% in group II, and 3%, 16%, 29% and 32% in group III. Significant difference
      was found between group I and group II in sputum negative conversion rate in 2nd
      month after treatment (P < 0.05). After treatment, values of lymphocyte
      transformation test (LTT), CD(3), CD(4) and CD(4)/CD(8) of the above 3 groups
      were all higher than that before the treatment (P < 0.05), level of tumor
      necrosis factor decreased in group II and IL-2, IL-6 increased in group III.
      CONCLUSIONS: Vaccine of Mycobacterium vaccae is a good immunotherapy preparation,
      which promotes sputum negative conversion and activation of cell-mediated
      immunity.

PMID- 11820959
TI  - [Are we diagnosing people infected with HIV in time?].
AB  - OBJECTIVE: To describe the number of AIDS cases who did not know of their HIV
      infection until they developed AIDS, and the factors relating to this situation.
      DESIGN: Descriptive study of data of the National AIDS Register.Setting.
      Spain.Patients. Cases of AIDS in the over-14s diagnosed between 1997 and 1999.
      RESULTS: Of the 6910 cases of AIDS studied, 35% (n = 2421) knew that they were
      HIV-positive at the same time as they were diagnosed with AIDS (in the same month
      or the previous one). The multi-variate analysis showed that this situation
      occurred less commonly in women (OR = 0.61; 95% CI, 0.53-0.71), in cases
      diagnosed in prison (OR = 0.19; 95% CI, 0.13-0.27), in cases diagnosed early (OR
      = 0.49; 95% CI, 0.41-0.60) and among residents in provinces with AIDS rates
      higher than the Spanish average (OR = 0.88; 95% CI, 0.78-0.99). Ignorance of HIV
      infection until the AIDS diagnosis was associated to ages of under 25 and over
      34, homo/bisexual transmission (OR = 3.20; 95% CI, 2.69-3.80) and heterosexual
      transmission (OR = 4.88; 95% CI, 4.21-5.65) compared with intravenous drug users,
      and to the person coming from countries other than Spain, both developed (OR =
      2.78; 95% CI, 1.89-4.08) and under-developed (OR = 1.85; 95% CI, 1.26-2.72)
      countries. CONCLUSIONS: A considerable number of people diagnosed with AIDS were
      unaware of their HIV infection, especially among people who had never injected
      drugs. HIV needs to be diagnosed earlier so as to improve prevention and
      treatments.

PMID- 11820958
TI  - [Do the morning peak in blood pressure, age and gender affect the need to change
      hypertension treatment because of inefficacy?].
AB  - OBJECTIVE: To evaluate if the timing coincidence of morning rise of arterial
      blood pressure (BP) and morning turn of clinic BP measurement in our primary
      healthcare center implies an increased risk of switching antihypertensive drugs
      because of inefficacy with respect to afternoon staff turn. We also describe age
      and sex differences. DESIGNAND SETTING: A historical cohort study. We recorded
      all changes of antihypertensive drugs because of inefficacy of patients of 7
      urban primary care clinics during the period from october 1997 to september 1999.
      MEASUREMENTS: We compared the incidence of changes per 1000 months of
      prescription of morning and afternoon turns, men and women, older and younger
      patients than 75 and 65 years old. RESULTS: The mean age of 1152 patients was
      69.5 years old. The relation men:women in morning and afternoon turns was
      similar. Relative risk of switching in morning/afternoon turns was 0.82 (95% CI,
      0.61-1.10). Sex and age did not affect the results. If the turn was not
      considered, younger patients and men had increased risk of being switched. Male
      adults (< 65 years old) relative risk against female was 1.62 (95% CI, 1.07
      2.47). Older patients than 65 year had the RR inverted: RR men/women: 0.78 (95%
      CI, 0.51-1.21). CONCLUSION: Morning rise of BP did not provoque an increased risk
      of switching antihypertensive drugs in morning turn with respect to afternoon
      turn. Male adults had increased risk of switching with respect to women. Older
      women than 65 years old had more risk than men to be changed.

PMID- 11820960
TI  - [Community activities in primary care in Spain. An analysis based on the network
      of the Program of Community Activities (PACAP)].
AB  - OBJECTIVE: To describe, analyse and discuss the activities in the Network of
      Community Activities of the Programme of Community Activities in Primary Care of
      the Spanish Society of Family and Community Medicine. DESIGN: Description of the
      activities within this Network.Setting. Network of Community Activities of the
      Spanish Society of Family and Community Medicine. MAIN MEASUREMENTS:
      Specifications of the variables of geography, target population and experience
      descriptives were obtained from the qualitative analysis of the activity summary
      composed by its authors. The measurements are frequency tables expressed in
      graphs and analysis of the summaries contributed by the groups on objectives,
      kinds of programme, methodologies, evaluation and conclusions reached. The
      community orientation activities undertaken by the health centres registered on
      the Network came mostly (54%) from the autonomous communities of Madrid and
      Andalusia. A great many of them were aimed at the adult population, tackling
      problems of chronic diseases, and particularly at women, in this case tackling
      gender themes such as menopause and pregnancy, etc. CONCLUSIONS: There was uneven
      distribution between autonomous communities of the experiences included on the
      web. Central to community orientation are the replies to questions such as:
      inside or out of the health centre?, the importance of transferring leadership to
      society, and adaptation to the needs and demands of the population cared for.

PMID- 11820961
TI  - [Does the anti-thrombin III test need to be done for women taking oral
      contraceptives?].

PMID- 11820962
TI  - [Family medicine in the monitoring of hypothyroidism].

PMID- 11820963
TI  - [Oral leukoplakia].

PMID- 11820964
TI  - [Basis and objectives of palliative treatment].

PMID- 11820965
TI  - [The Web as a resource for statistical and medical-administrative information].

PMID- 11820967
TI  - [Toxicoderma associated with alendronate].

PMID- 11820966
TI  - [Brugada syndrome. Report of a case].

PMID- 11820969
TI  - [Clinical analyses and primary care].

PMID- 11820970
TI  - [The second semFYC's smokeless week: how many smokers are prepared to stop
      smoking in primary care and what can we do to help them?].

PMID- 11820968
TI  - [Urinary infections without complications: comparison of a treatment with
      norfloxacin for 7 days versus norfloxacin for 3 days].

PMID- 11820971
TI  - [The journal].

PMID- 11820973
TI  - [Tuberculous spondylodiskitis (Pott's disease): Experience in a general
      hospital].
AB  - BACKGROUND: Pott's disease (PD) is an uncommon extra-pulmonary form of
      tuberculosis. Dissimilar data about location, diagnosis and treatment from
      various hospitals and different countries are reported. PATIENTS AND METHOD: We
      present our experience with Pott's disease at our institution between January
      1993 to December 1999, retrospectively, based on clinical bacteriological and
      pathological research. We found the medical records of 14 patients diagnosed as
      having PD at our hospital. The following information was obtained: age, sex,
      symptoms and sings at presentation, PPD tuberculin skin test, imaging techniques,
      mycobacterium cultures and smear, histopathologic study, treatment and clinical
      outcome. RESULTS: The number of microbiological diagnosed tuberculosis during the
      study period was of 1,400 (4 cases per 1,000 admissions). From them, 1,047 cases
      (74.8%) were pulmonary and 353 cases (25.2%) extra-pulmonary. We found the
      medical records of 14 patients diagnosed as having PD at our hospital. There was
      a diagnostic delay between 2 and 720 days. In 5 cases, cultures were positive
      (1.4% extra-pulmonary). The following information was obtained: age, sex,
      symptoms and signs at presentation, PPD tuberculin skin test, imaging techniques,
      mycobacterium cultures and smear, histopathologic study, treatment and clinical
      outcome. The mean age of the patients was 58 years. Pain and dorsal location were
      more frequent (8/14). In 6 cases, tuberculosis was diagnosed at other sites.
      Tuberculin skin test was positive in 7 ases (50%). The diagnosis was confirmed by
      positive cultures from biopsies in 5 from 8 cases performed and the histology was
      compatible in 8 from 11 cases performed. Diskitis was presented in 10 cases, soft
      tissue abscess in 9 cases (psoas abscess in 2); epidural compression in 9 cases
      and surgery was necessary in 9 cases (diagnostic in 3). CONCLUSIONS: Pott's
      disease is a rare entity even among HIV-patients in whom extrapulmonar disease
      has increased. Dorsal location, diskitis and advanced forms of the disease that
      deserve surgical treatment are frequent.

PMID- 11820974
TI  - [Comparison of three ELISA techniques for the evaluation of IgG seroprevalence
      against Bordetella pertussis in children vaccinated with three doses of DTPwc].
AB  - BACKGROUND: Although there are several ELISA procedures to determine IgG against
      Bordetella pertussis, there are scarce data that allow to compare the
      seroprevalence detected using different kits. The objective of this study was to
      evaluate and to compare by three ELISA techniques the seroprevalence against B.
      pertussis in children. PATIENTS AND METHOD: 172 children 6-10 years old,
      vaccinated with three dose of DTPwc were studied. IgG against Bordetella
      pertussis was determined by two quantitative techniques (Labsystems and Serion).
      The qualitative detection of IgG against FHA and PT was performed by a
      semiquantitative method (Pertusscan). RESULTS: The Labsystems ELISA classified a
      42.4% of the samples as positive and a 32% as borderline. The Serion method
      showed 52.9% of positive and 20.9% of borderline results. IgG-FHA was detected in
      81.4% and IgG-PT in 75% of the samples by Pertusscan. The level of "immunity"
      recommended by this method was of 21.5%. The agreement between Labsystems and
      Serion was 45.9% (kappa index 5 0.157; p < 0.01). In the IgG-TP or IgG-FHA
      positive samples, the proportion of positive results obtained by Serion was
      superior to those obtained by Labsystems while the number of borderline results
      were inferior (p < 0.05). CONCLUSIONS: Both quantitative techniques showed a high
      rate of not conclusive results and a very weak concordance. The large number of
      doubtful results obtained by Labsystems and its worse concordance with the other
      techniques dissuades its employment in inmunogenicity studies. The results
      obtained by the other two techniques present a problematic interpretation in
      terms of seroprevalence.

PMID- 11820975
TI  - [Salmonella enteritis in Huesca. 1996-1999].
AB  - BACKGROUND: The enteritis due to Salmonella is still an important cause of
      infectious gastroenteritis, that is responsible of 85% of the foodborne outbreaks
      in Spain. It represents without any doubt a public health problem that involves
      several health care services and preventive services. SUBJECTS AND METHOD: Using
      two sources of information: the National Diseases Surveillance System and the
      Microbiology Laboratories of the Hospitals (MLH) we estimated the incidence of
      Salmonella infection by the capture-recapture method. Besides, a descriptive
      study of the disease is done and the more frequent serogroups in the province of
      Huesca during the period 1996-1999. RESULTS: The total number of cases was 959,
      which means a media annual rate of 116.6 3 105. The estimated number of cases was
      1,145 (media annual rate 5 139.5 3 105). The completeness is higher for the MLH
      (68%, CI 95%: 66-71). The group D is the more frequent (53.4%) and of this,
      specially the Salmonella enteritidis. 31% of the cases are under 5 years, and
      38.2% are admitted to the hospital. The cases appear seasonally from May to
      September, with an important peak during the month of August. CONCLUSIONS: The
      improve in the notification and identification of cases by the reporting sources
      and by the Laboratory Services allowed us to better know the disease. Our results
      and the proportion of groups-serotypes are similar to the results of other
      studies.

PMID- 11820976
TI  - [Efficacy of two semiautomatic methods for bacteriuria detection].
AB  - BACKGROUND: A quick and reliable method for detecting bacteriuria would allow to
      exclude the presence of microorganisms in the urine on the same day the sample is
      obtained.Objectives. Two semiautomatic methods have been evaluated for
      bacteriuria screening, taking the semiquantitative culture as reference method.
      MATERIAL AND METHOD: A prospective study of urine samples from patients suspected
      of having a urinary infection was designed. One method is based on
      bioluminescence that detects the presence of ATP liberated by the bacterial cell
      (Utiscreen-Coral Biomedical). The other semiautomatic method uses a nephelometry
      technique (Uro-quick). The results of each semiautomatic method were compared
      with the semiquantitative culture. Samples presenting counts > 104 UFC/ml of one
      or two microorganisms were considered as having urinary-tract infection
      (equivalent to significative bacteriuria). Cultures with counts < 5,000 UFC/ml or
      containing three or more microorganisms were classified as non-representative of
      significant bacteriuria. The nephelometric system allows to obtain results at two
      different times. Samples were divided into two groups to compare both situations.
      RESULTS: 1,090 urine samples, received consecutively, were considered. In the
      case of the bioluminescence system, the study was prolonged to 1,565 samples. The
      values obtained were: a) bioluminescence: general data, sensibilitiy (S) 5 94.4%;
      especificity (E) 5 72.8%; positive predictive value (PPV) 5 46.2% and negative
      predictive value (NPV) 5 98.2%; hospitalized patients only, S 5 97.5%; E 5 77.3%;
      PPV 5 61.2% and NPV 5 98.8%; and b) nephelometry: 195 min, S 5 96.7%; E 5 88.8%;
      PPV 5 67.9% and NPV 5 99.1%; 235 min, S 5 95.5%; E 5 81.0%; PPV 5 58.7% and NPV 5
      98.4%. CONCLUSION: A negative predictive value from both methods under these
      conditions would allow them to be used in medical centers for the exclusion of
      bacteriuria.

PMID- 11820977
TI  - [In vitro susceptibility study of herpes simplex virus to acyclovir and
      foscarnet. Are routine susceptibility studies necessary?].
AB  - BACKGROUND: The objective of this study was to investigate the prevalence of
      resistance of herpes simplex virus to acyclovir and foscarnet. PATIENTS AND
      METHOD: An in vitro susceptibility study of HSV strains isolated from HIV
      infected and non-infected (control group) patients was conducted by means of
      qualitative screening. When the screening results were positive, the method for
      reducing cytopathic effect was utilized for calculating ID50. An ID50 < 1
      microgram/ml indicated susceptibility to acyclovir, ID50 1-2 microgram/ml was
      intermediate susceptibility to acyclovir and a value of ID50 >/= 2 microgram/ml
      denoted resistance. Resistance to foscarnet was considered at ID50 >/= 100
      microgram/ml. RESULTS: The study involved investigating 84 HSV strains, 49 HIV
      infected patients, and 19 control patients. In the control group, no strains
      resistant to acyclovir were present and infection recurred in only one patient.
      In patients with HIV infection, one acyclovir resistant strain was detected and
      one moderately resistant to acyclovir, with good response to acyclovir treatment.
      In this group, 24.4% of patients presented recurrent infection. No resistance to
      foscarnet was detected. CONCLUSION: Percentage of HSV strains resistant to
      acyclovir is very low and resistance to foscarnet was not detected. These data
      suggest that routine in vitro susceptibility testing of antiviral drugs against
      HSV does not seem to be necessary.

PMID- 11820978
TI  - [What's new in bacterial resistance to antimicrobials?].

PMID- 11820979
TI  - [Edematous-erythematous lesion on the finger of a cattle farmer].

PMID- 11820980
TI  - [Lytic lesion in the femoral condyle in a female patient with human
      immunodeficiency virus infection].

PMID- 11820981
TI  - [Staphylococcus lugdunensis pneumonia].

PMID- 11820982
TI  - [Liver abscess due to Salmonella typhi].

PMID- 11820984
TI  - [Lipodystrophic syndrome associated with human immunodeficiency virus. Is there a
      relationship with hepatitis C virus infection?].

PMID- 11820983
TI  - [Group A beta-hemolytic Streptococcus necrotizing fascitis secondary to muscular
      effort].

PMID- 11820985
TI  - [Spontaneous bacterial peritonitis due to Listeria monocytogenes].

PMID- 11820988
TI  - [Spondylodiscitis and epidural abscess due to Citrobacter freundii].

PMID- 11820986
TI  - [Keratitis due to Mycobacterium chelonae after refractive surgery with LASIK].

PMID- 11820987
TI  - [Pleuropericarditis due to Mycoplasma after coronary bypass].

PMID- 11820994
TI  - [New stage in our web page].

PMID- 11820989
TI  - [Purulent pericarditis due to Salmonella enterica subsp. arizonae].

PMID- 11820995
TI  - [Determination of insulin, leptin and neuropeptide y by radioimmunoanalysis in
      patients with morbid obesity and anorexia nervosa after therapeutic
      intervention].
AB  - The present study was conducted in order to analyze the relationship existing
      between leptin, insulin and neuropeptide Y (NPY) levels in massive weight loss
      and weight recovery. Twenty-three patients with severe obesity, 23 patients with
      anorexia nervosa and 28 healthy control subjects were studied. Patients with
      severe obesity underwent a vertical banded gastroplasty followed by an 800
      kcal/day diet during 16 weeks, with evaluation taking place before (Body mass
      index, BMI, 52,1 8 Kg/m2) and after the drastic weight loss (BMI 39,2 6,2 Kg/m2).
      Patients with anorexia nervosa were treated with nutritional therapy exclusively
      during 16 weeks, and they were evaluated in the low weight situation (BMI 15,3
      1,7 Kg/m2) and after weight recovery (BMI 18,9 2,8 Kg/m2). Normal subjects had a
      normal BMI from 20 to 27 (average 21,8 2 Kg/m2). BMI, percentage of body fat, and
      serum levels of leptin, insulin, and NPY, were determined in each patient and
      normal subjects. In severe obese patients serum leptin and insulin decreased
      significantly after drastic weight reduction (leptin: from 48,8 19,2 to 24,3 9,8
      ng/ml; insulin: from 26,2 10,8 to 18 6 U/ml). In patients with anorexia nervosa
      serum leptin mean levels were significantly higher after weight recovery (3,7 1,9
      vs 9,2 5,1 ng/ml). In subjects with morbid obesity NPY levels decreased after
      weight loss below those of control group (43,5 16,1 vs 57,3 12,8 pmol/l). On the
      other hand, patients with anorexia nervosa had NPY levels superior to those of
      control group. In subjects with anorexia, NPY levels decreased after weight
      recovery (69,1 16,7 a 59,1 20,3 pmol/l). In the whole population, Leptin and NPY
      plasma levels were correlated with body fat percentage. Leptin was positively
      correlated with BMI and body fat percentage in obese and anorectic subjects after
      weight loss or recovery, respectively. NPY was inversely correlated with body fat
      percentage in controls and obese subjects before treatment. These data reveal
      that the concentration of serum leptin and NPY correlates significantly with the
      total adiposity in subjects with a wide weight range and caloric intake. Leptin
      plasma levels are proportional to fat stores in patients with severe obesity and
      anorexia nervosa after drastic weight loss or recovery, respectively. NPY serum
      levels are negatively correlated with de total body fat in normal weight subjects
      and obese patients in their initial weight.

PMID- 11820996
TI  - [Isotopic renal study in diabetic nephropathy].
AB  - This study aimed to evaluate the prognostic value of the kidney split function
      (KSF), the effective renal plasma flow (ERPF) and glomerular filtration rate (GF)
      in the evolution of diabetic nephropathy. MATERIAL AND METHODS: 125 patients
      (IDDM:10, NIDDM:115), including 62 men, ages 18-84 years, were studied. In all
      cases GF (Cr 51 EDTA), ERPF (131I-hippuran), kidney split function (obtained from
      the 99mTc-MAG3 renogram) and basal serum creatinine (SC) were evaluated at the
      beginning of the study and patients were clinically followed up for 5 years by
      SC. Ultrasound and/or intravenous digital angiography were performed in 120
      patients. RESULTS: In patients with decreased ERPF (76 patients) the SC increased
      progresively during the 5 years, in both those with elevated PC (N = 54) as well
      as in those with normal baseline SC (n = 22). In patients with normal ERPF the SC
      did not change significantly during the study. An asymethric split function (KSF
      < 40% in one kidney) was found in the renogram of 42 patients; in 32 of them the
      ERPF was decreased. Of these, ulttrasonography was normal in 9, and vascular
      and/or obstructive pathology was demonstrated by ultrasonography or digital
      angiography in only 6 patients. CONCLUSION: The ERPF becomes altered earlier than
      serum creatinine in patients with diabetic nephropaty. ERPF and split function
      calculation, and FG seems to have higher prognostic value than ultrasounds in the
      management of diabetic nephropathy. Radionuclides seems to be an accurate test
      than the ultrasonography to detect renal function abnormalities in patients with
      diabetic and thus can be an examination of choice in these patients.

PMID- 11820997
TI  - [Detection of the cutaneous melanomas, their metastasis and relapses by
      scintigraphies with 99MTC-HMPAO].
AB  - A pilot study was carried out in the Nuclear Medicine Department of the National
      Institute of Oncology and Radiobiology to learn the diagnostic efficacy of the
      99mTc-HMPAO scintigraphy in the detection of cutaneous melanoma, distant and
      local metastases, in patients with a confirmed histological diagnosis. The planar
      and/or SPECT scintigraphy was performed in 17 patients and revealed 90%
      sensitivity for the detection of the disease. We calculated the tumor/background
      index in all the images obtained and found a value greater than 1 in every case.
      Thus, we can affirm that the 99mTc-HMPAO accumulation in tumors was higher than
      the background in all cases. We recommend that this procedure be considered in
      the follow up of these patients as a new diagnostic method which is very useful
      in the determination of the patient stage and prognostic evaluation.

PMID- 11820998
TI  - [No influence of propanolol, cyclosporine, adriamycin, and nifedipine on the in
      vitro labelling of erythrocytes].
AB  - The objective of this work was to study the potential interference of propanolol,
      cyclosporine, adriamycin, and nifedipine with the in vitro labelling of
      erythrocytes. MATERIALS AND METHODS: 20-ml blood specimens were collected from 40
      healthy volunteers who had not taken any drug in the week before collection. 2.0
      ml alliquots were incubated at 37 C with different concentrations of the drugs
      for 30 minutes. In all cases, a control group was incubated with saline (0.9%).
      Two labelling methods were used: 1) EDTA method, in which 60 l of SnCl2 (10.2
      g/ml), 2.0 ml of saline, 0.2 ml EDTA 2.2%, and 7.4 MBq of Na99mTcO4 were added,
      and the mix was incubated for 5 minutes. 2) The hypochlorite method, in which
      specimens were initially incubated with SnCl2 (10.2 g/ml) for 5 minutes. Then, 40
      l of 1% hypochlorite and all the reagents described in the previous method were
      added. With both methods, erythrocytes were separated by centrifugation and the
      labelling yield was estimated. RESULTS: RESULTS did not show significant
      differences between the yield of the control group labelling and the yield of the
      different concentrations of the tested drugs. Also, significant differences were
      not observed the two labelling methods used. CONCLUSION: Both labelling methods
      are useful for the in vitro preparation of 99mTc-erythrocytes. The absence of
      significant differences in the labelling yield indicates that in vitro
      interferences observed by some investigators are associated with concentrations
      exceeding therapeutic plasma levels. On the other hand, the reported in vivo
      interferences might be due to the presence of active catabolites and/or
      interference between different drugs.

PMID- 11821000
TI  - [FGD PET in a patient with pseudofractures from osteomalacia].
AB  - We present the case of a 42 year old man, with a history of multiple fractures
      and generalized pain for two years. A three phase bone scan, demonstrated
      multiple fractures involving the ribs, both ankles and feet. After going through
      a battery of tests which included an FDG PET scan (to exclude an occult
      malignancy), the patient was diagnosed with osteomalacia and hyperparathyroidism.
      The FDG PET scan, demonstrated multiple foci of increased FDG uptake throughout
      the axial skeleton, in a pattern highly suggestive of pseudofractures, rather
      than osseous metastases.

PMID- 11820999
TI  - [Analysis of the cytosolic content of the pS2 protein in breast cancer].
AB  - OBJECTIVE: To analyze pS2 cytosolic levels in breast carcinomas and their
      correlation with different clinical characteristics of the patients and their
      tumours. MATERIAL AND METHODS: Cytosolic pS2 levels were measured by
      radioimmunometric assay in tumours from 168 breast cancer patients. RESULTS: The
      pS2 values ranged from 0 to 251 ng/mg protein (mean SD: 21.8 38.1; median: 7.9
      ng/mg protein). These protein levels were significantly (p < 0.05) higher in
      premenopausal patients (27.6 45.2) than in postmenopausal patients (19.5 33.8).
      Intratumour pS2 levels were also significantly (p < 0.05) correlated with
      histologic grade of the tumours, and were higher in well diferentiated tumours
      (grade I: 28.8 42.8) than in moderately differentiated tumours (grade II: 19.7
      35.6) and than in poorly differentiated tumours (grade III: 18.9 37.3).
      Similarly, significant differences in pS2 content were found between positive
      estrogen receptor (ER) tumours and ER-negative tumours (29.1 46.5 vs 11.3 15.9,
      respectively; p<0.0001), as well as between positive progesterone receptor (PR)
      tumours and PR-negative tumours (29.1 49.8 vs 15.3 21.5, respectively; p < 0.05).
      CONCLUSIONS: The results suggest that pS2 may be a useful prognostic marker in
      breast cancer, and may also be useful to identify patients who are likely to
      benefit from hormone therapy.

PMID- 11821002
TI  - [Cerebral positron emission tomography with F18-fluorodeoxyglucose].

PMID- 11821001
TI  - [Importance of lateral projections in the diagnosis of brain death].

PMID- 11821003
TI  - [Positron emission tomography (PET) in oncology (Part I)].

PMID- 11821004
TI  - [Secreted tumor markers and breast cancer].
AB  - The tumor secretion markers used most in the daily practice are reviewed,
      emphasizing the physiological aspects having great practical usefulness.
      Likewise, the possible value of other recently described substances which could
      be introduced into the daily practice in the near future is explained.

PMID- 11821005
TI  - PSA-NCAM expression in the piriform cortex of the adult rat. Modulation by NMDA
      receptor antagonist administration.
AB  - Administration of NMDA receptor antagonists upregulates the expression of the
      polysialylated form of the neural cell adhesion molecule (PSA-NCAM) in the adult
      hippocampus. Since the piriform cortex is also populated by PSA-NCAM
      immunoreactive neurons during adulthood, we sought to characterize them in detail
      and to test whether NMDA receptor antagonists also modulate PSA-NCAM in this
      cortical region. PSA-NCAM immunoreactivity is located mainly in layer II, where
      many neurogliaform and some pyramidal-semilunar transitional neurons are labeled.
      Many large neurons in layer III and endopiriform nucleus also express PSA-NCAM.
      Interestingly, some small labeled cells resembling migratory neuroblasts appear
      in these layers and in the ventral end of the corpus callosum subjacent to the
      piriform cortex. These putative migratory cells and some neurogliaform neurons in
      layer II do not express NeuN, a marker of differentiated neurons. Many of these
      PSA-NCAM immunoreactive cells also express doublecortin, a molecule involved in
      neuronal migration. The number of PSA-NCAM immunoreactive neurogliaform neurons
      increases significantly 7 days after the administration of an NMDA receptor
      antagonist. Moreover, 21 days after the treatment we observe a significant
      increase in the number of doublecortin expressing cells in the deep layers of the
      piriform cortex. These results expand the current knowledge of the neuronal
      populations expressing PSA-NCAM in the piriform cortex, suggesting that some of
      these cells could be involved in structural plastic events such as axonal
      outgrowth, synaptogenesis or even neuronal migration. Similar to the hippocampus,
      NMDA receptors appear to play a critical role in these processes in the adult
      piriform cortex.

PMID- 11821006
TI  - Muscarinic modulation of hypoxia-induced release of catecholamines from the cat
      carotid body.
AB  - Chemotransduction of arterial hypoxemia by the cat carotid body is generally
      thought to begin with a hypoxia-induced depolarization of the glomus cells (GCs)
      of the carotid body (CB). This depolarization activates voltage-gated calcium
      channels with the subsequent entry of calcium, movement of transmitter-containing
      vesicles to the synaptic-like juncture between the GC and apposed sensory
      afferent neuron. The vesicles exocytotically release their transmitters which
      then proceed to the receptors on both the postsynaptic neuron and on the GCs
      themselves (autoreceptors). Action potentials and their modulation in the sensory
      fibers are the result, along with the modulation of further neurotransmitter
      release from the GCs. The purpose of the present study was to: (1) determine the
      parameters of an incubated cat CB preparation capable of releasing measurable
      amounts of catecholamines (CAs) in response to hypoxia; (2) determine the impact
      of muscarinic activities on CA release during the hypoxic challenge; (3)
      determine if the muscarinic activity preferentially modified the release of one
      CA more than another; (4) determine if there were any differences in the pattern
      of hypoxia-induced release of dopamine (DA) vs. norepinephrine (NE). CBs were
      harvested from deeply anesthetized cats. Cleaned of fat and connective tissue,
      they were incubated in Krebs Ringer bicarbonate solution at 37 degrees C, and
      bubbled with a hyperoxic mixture of gases (95% O(2)-5% CO(2)) for 30 min. The
      first series of experiments to address the CB's hypoxia-induced release of CAs
      explored the effects of incubating CBs for 2 h with hyperoxia vs. normoxia (21%
      O(2)-6% CO(2)) followed by a 30 min hypoxic challenge, with or without L
      dihydroxyphenylalanine (L-DOPA). In the second series of experiments the CBs,
      after the first 30 min of hyperoxia, were next challenged with hypoxia (4% O(2)
      5% CO(2)) for intervals of 3-20 min with intervening recovery periods of
      hyperoxia to determine the effect of the duration of the hypoxic exposure on CA
      release. In the third series of experiments the CBs, after the first 30 min of
      hyperoxia, were challenged with hypoxia for intervals of 10-40 min in the
      presence or absence of an M1 or M2 muscarinic receptor antagonist. CAs released
      into the incubation medium were analyzed by means of high performance liquid
      chromatography-electrochemical detection using standard procedures. Incubated cat
      CBs challenged for 2 h with hyperoxia followed by 30 min of hypoxia, released
      much more measurable amounts of CAs in the presence of 40 microM L-DOPA than
      without it. Moving from hyperoxia to hypoxia produced a better yield than moving
      from normoxia to hypoxia, and at least 10-20 min exposures were needed for
      measurable amounts of CAs. The M1 muscarinic receptor antagonist, pirenzepine,
      reduced the hypoxia-induced release of CAs during each exposure. Further, the
      reduction appeared to be dose-related. The M2 muscarinic receptor antagonist,
      methoctramine, enhanced the hypoxia-induced release of CAs during each exposure.
      These data support a role for acetylcholine (ACh) in the hypoxia-induced release
      of CAs, and suggest a significant, if modest, muscarinic dimension to it. And
      although hypoxia induced a greater release of DA than of NE, the muscarinic
      modulation of the release (both decreasing it and increasing it) may have had a
      greater impact on NE release than on DA release. Finally, the patterns of hypoxia
      induced release of DA and NE from incubated cat carotid bodies are significantly
      different.

PMID- 11821007
TI  - Peripheral and central administration of neuropeptide Y in a rat middle cerebral
      artery occlusion stroke model reduces cerebral blood flow and increases infarct
      volume.
AB  - Recent studies have shown increased immunoreactivity for neuropeptide Y (NPY)
      within the perilesional cortex following experimental middle cerebral artery
      occlusion (MCAO) or focal excitotoxic damage. Downregulation of the NPY Y1
      receptor gene using an antisense oligodeoxynucleotide produced a doubling of the
      infarct volume, implying that NPY may mediate neuroprotection against focal
      ischemia. The effects of treatment with NPY on infarct volume and hemodynamic
      parameters were investigated in the present study. Adult male Sprague-Dawley rats
      were anesthetized with sodium pentobarbital to undergo right-sided endovascular
      MCAO for 2 h. A single dose of NPY was given via intracarotid injection (10
      microg/kg) at the beginning of reperfusion, intracisternal injection (10 or 30
      microg/kg) at 30 min of ischemia, or intracerebroventricular (i.c.v.) injection
      (10 or 70 microg/kg) at 30 min of ischemia. Control groups received the vehicle
      only via the same route. Body temperature was maintained constant, and
      hemodynamic parameters were monitored during anesthesia. Laser Doppler flowmetry
      was used to monitor the regional cerebral blood flow (rCBF) during ischemia and
      reperfusion in some rats. The rats were decapitated on day 3, and their brains
      were cut into 2-mm thick coronal slices before reaction with a 2% solution of
      2,3,5-triphenyltetrazolium chloride to reveal the infarct. Compared to the
      respective control groups, NPY treatment via any method of administration
      increased the relative infarct volume. Suppression of rCBF was observed during
      reperfusion. These results indicate that peripheral or central administration of
      NPY impairs reperfusion following experimental MCAO and worsens the outcome of
      focal cerebral ischemia.

PMID- 11821008
TI  - Cellular mechanisms by which tumor necrosis factor-alpha produces disruption of
      the blood-brain barrier.
AB  - The first goal of the present study was to determine the effect of tumor necrosis
      factor-alpha (TNF-alpha) on the permeability of the blood-brain barrier in vivo.
      The second goal of this study was to investigate cellular pathways responsible
      for changes in permeability of the blood-brain barrier in response to TNF-alpha.
      We examined the pial microcirculation in rats using intravital fluorescence
      microscopy. Permeability of the blood-brain barrier was quantitated by
      calculating the clearance of fluorescent-labeled dextran (mol. wt=10,000; FITC
      dextran-10K) during superfusion with vehicle, tumor necrosis factor (TNF-alpha;
      10 ng/ml), TNF-alpha in the presence of an inhibitor of soluble guanylate cyclase
      (ODQ; 1.0 microM), and TNF-alpha in the presence of an inhibitor of protein
      tyrosine kinase (genistein; 10 microM). During superfusion with vehicle,
      clearance of FITC-dextran-10K from pial vessels remained relatively constant
      during the experimental period. In contrast, superfusion with TNF-alpha markedly
      increased clearance of FITC-dextran-10K from the cerebral microcirculation.
      Topical application of ODQ and genistein, significantly inhibited increases in
      permeability of the blood-brain barrier to FITC-dextran-10K during application of
      TNF-alpha. Thus, TNF-alpha increases the permeability of the blood-brain barrier
      to a moderately sized molecule via a mechanism which appears to involve
      activation of soluble guanylate cyclase and protein tyrosine kinase. In light of
      evidence suggesting that TNF-alpha production is increased during cerebrovascular
      trauma, we suggest that the findings of this study may contribute to our
      understanding of the pathogenesis of disruption of the blood-brain barrier during
      brain trauma and inflammation.

PMID- 11821009
TI  - A co-culture-based model of human blood-brain barrier: application to active
      transport of indinavir and in vivo-in vitro correlation.
AB  - The growing array of in vitro models of the blood-brain barrier (BBB) which have
      been used makes it difficult to draw firm conclusions concerning the BBB
      penetration of HIV-1 protease inhibitors. What is needed is a combined in vivo
      and in vitro study on biological models that mimic as closely as possible the
      normal human BBB, to establish whether and how indinavir crosses the BBB. We
      developed a new human BBB model using primary endothelial cells and astrocytes.
      The biological relevance of this model was checked with respect on the one hand,
      to the close relationship between the log of drug permeability coefficient
      normalized to molecular weight and the log of the 1-octanol/water partition
      coefficient, and on the other hand to the functional P-glycoprotein (P-gp)
      expression. We employed this model to perform transport studies with indinavir
      and showed that the rate of in vitro indinavir transport from the basal to apical
      compartment was higher than the rate of apical to basal transport. Pretreatment
      of the BBB model with the P-gp inhibitor, quinidine, significantly increased
      apical to basal transport. Intracellular indinavir accumulation was increased in
      BBB as a result of inhibition of active transport. These data were correlated
      with the indinavir-mediated P-gp ATPase modulation showing that indinavir
      specifically interacted with a binding site on P-gp. Moreover, the activation of
      P-gp ATPase by indinavir was inhibited by quinidine. In addition, the in vivo
      brain to plasma concentration ratio of indinavir into mice showed that indinavir
      concentration was up to five times higher in the brain of mdr1a(-/-) mice than in
      the brain of mdr1a(+/+) mice. All these results confirm the role of P-gp in
      preventing the passage of indinavir across BBB and thus its entry into the
      central nervous system (CNS). Our human BBB model represents a useful tool for
      the evaluation of drug penetration into the CNS.

PMID- 11821010
TI  - Mechanism of 4-aminopyridine block of the transient outward K-current in
      identified Helix neuron.
AB  - The block of the transient outward K-current, I(K(A)) by 4-aminopyridine (4-AP)
      and blood-depressing substances (BDS) was investigated in identified Helix
      pomatia neurons (LPa3) using the two microelectrode voltage-clamp technique. The
      present study shows that 4-AP inhibits I(K(A)) in snail neurons in a voltage- and
      concentration-dependent manner. The 4-AP block of I(K(A)) involves the block of
      both open and closed states of the channel, however binding to open channels is
      preferred. It is suggested that 4-AP have two binding sites on the identified
      Helix neuron. One site causes an open channel block, which affects the N-type
      inactivation, and binding to the second site induces closed channel block, which
      affects C-type inactivation. In control solution the inactivating phase of the
      current is biexponential, suggesting simultaneous presence of two types of
      inactivation. The counterplay of these mechanisms results in the crossover of the
      current traces recorded from control and 4-AP blocked channels. It is assumed
      that use-dependence does not occur through blocker 'trapping', but rather by a
      different mechanism. BDS had no effect on Helix I(K(A)), suggesting that
      transient potassium channels in LPa3 neuron are not Kv3.4 type channels.

PMID- 11821011
TI  - Cyclosporin A, FK506 and rapamycin produce multiple, temporally distinct, effects
      on memory following single-trial, passive avoidance training in the chick.
AB  - Few studies have used a pharmaco-behavioural methodology to directly investigate
      roles for the calcium-dependent protein phosphatase calcineurin (CaN) in memory
      formation, due partly to the absence of specific inhibitory agents. A number of
      drugs with different inhibitory profiles were used to examine this issue in
      groups of chicks trained on a single-trial, passive-avoidance task. Bilateral
      intracranial administration of the immunosuppressants FK506 and cyclosporin A
      (CyA) led to two temporally distinct effects, distinguished by the concentration
      of drug required and the effective time of administration relative to training.
      In addition to inhibiting CaN, CyA and FK506 inhibit distinct classes of peptidyl
      prolyl-cis/trans-isomerases (PPIases). Other agents known to inhibit these
      enzymes, including the Map kinase inhibitor Rapamycin, also induced memory
      deficits in a complex, dose- and time-of-administration-dependent, manner. The
      data fail to conclusively implicate CaN in memory formation, but are consistent
      with proposals that a phosphatase cascade may participate in an early stage of
      information storage. PPIases may be required at a later stage to catalyse the
      folding of new or translocated proteins, the synthesis of which is required for
      formation of long-term memory, although other possible explanations for the data
      remain to be investigated.

PMID- 11821012
TI  - Effects of angiotensin blockade in the rostral ventrolateral medulla on
      maintenance of hypertension induced by chronic L-NAME treatment.
AB  - The major aim of the present study was to evaluate the role of the angiotensin II
      receptors located within the rostral ventrolateral medulla (RVLM) in the
      maintenance of high blood pressure following chronic nitric oxide inhibition.
      Rats were treated orally with L-NAME (70 mg/kg/day) for 1 week. We inhibited the
      RVLM neurons using drugs such as Sarthran, Losartan and glycine in urethane
      anesthetized rats (1.2 to 1.4 g/kg, i.v.). (1) Bilateral microinjection of
      Sarthran into the RVLM decreased BP in the hypertensive and normotensive groups,
      but the depressor effect of the drug was lower in hypertensive than in
      normotensive rats. (2) The decrease in BP in response to Sarthran in the RVLM
      compared with glycine was significantly smaller in the hypertensive group, but
      not in the normotensive group. (3) No change in MAP was observed in response to
      bilateral microinjection of the Ang AT(1) receptor antagonist Losartan into the
      RVLM in either group. These results suggest that (1) the endogenous angiotensin
      receptors of the RVLM are involved in the maintenance of high BP in L-NAME
      treated animals and (2) the tonic action of Ang II is not dependent on AT(1)
      receptors within the RVLM. The possibility of an action via other Ang II
      receptors remains to be investigated.

PMID- 11821013
TI  - Differential distribution of afferents containing serotonin and neuropeptide Y
      within the marmoset suprachiasmatic nucleus.
AB  - Neuropeptide Y-containing fibers/terminals were immunohistochemically detected in
      the ventral portion of the marmoset suprachiasmatic nucleus, approximately
      matching the distribution of its retinal afferents. On the other hand,
      serotonergic fibers/terminals were found mostly in central and dorsal areas of
      the suprachiasmatic nucleus, almost completely sparing its ventral portion. These
      data may represent a morphological substrate for differential actions of
      serotonin and neuropeptide Y in the control of circadian rhythmicity in
      marmosets.

PMID- 11821014
TI  - Blockade effect of mu and kappa opioid antagonists on the anti-nociception
      induced by intra-periaqueductal grey injection of oxytocin in rats.
AB  - Intra-periaqueductal grey (PAG) injection of 1 nmol of oxytocin induced
      significant increases in hindpaw withdrawal latency (HWL) to thermal and
      mechanical stimulation in rats. The anti-nociceptive effect of oxytocin was
      attenuated significantly by subsequent intra-PAG injection of the mu opioid
      antagonist beta-funaltrexamine (beta-FNA) and the kappa opioid antagonist nor
      binaltorphimine (nor-BNI), but not by the delta antagonist naltrindole. The
      results demonstrated that mu and kappa opioid receptors, not delta receptors,
      were involved in the oxytocin-induced anti-nociception in PAG of rats.

PMID- 11821015
TI  - Angiotensin 1-7 increases quantal content and facilitation at the frog
      neuromuscular junction.
AB  - At the neuromuscular junction, several endogenous substances have been shown to
      act presynaptically to modify transmitter release. Here we show that angiotensin
      1-7, a vasoactive peptide of the renin-angiotensin system, increased quantal
      content in a dose-dependent manner, with a maximal increase of 78% at 250 nM. At
      the same dose, angiotensin 1-7 increased paired pulse facilitation by 70%. This
      is the first report of angiotensin 1-7 altering a cholinergic synapse.

PMID- 11821016
TI  - The highly selective cyclooxygenase-2 inhibitor DFU is neuroprotective when given
      several hours after transient cerebral ischemia in gerbils.
AB  - Several studies suggest that cyclooxygenase-2 contributes to the delayed
      progression of ischemic brain damage. In this study we examined whether the
      highly selective cyclooxygenase-2 inhibitor DFU reduces neuronal damage when
      administered several hours after 5 min of transient forebrain ischemia in
      gerbils. The extent of ischemic injury was assessed behaviorally by measuring the
      increases in locomotor activity and by histopathological evaluation of the extent
      of CA1 hippocampal pyramidal cell injury 7 days after ischemia. DFU treatment (10
      mg/kg, p.o.) significantly reduced hippocampal neuronal damage even if the
      treatment is delayed until 12 h after ischemia. These results suggest that
      selective cyclooxygenase-2 inhibitors may be a valuable therapeutic strategy for
      ischemic brain injury.

PMID- 11821017
TI  - Effects of extracellular Ca2+ influx on endothelin-1-induced intracellular
      mitogenic cascades in C6 glioma cells.
AB  - We have recently shown that endothelin-1 activates two types of Ca2+-permeable
      nonselective cation channels (NSCC-1 and NSCC-2) in C6 glioma cells. These
      channels can be distinguished by their sensitivity to blockers of the receptor
      operated Ca2+ channel, 1-[b-(3-[4-methoxyphenyl]propoxy)-4-methoxyphenethyl]-1H
      imidazole hydrochloride (SK&F 96365) and (R,S)-(3,4-dihydro-6,7-dimethoxy
      isoquinoline-1-yl)-2-phenyl-N,N-di-[2-(2,3,4-trimethoxyphenyl)ethyl]-acetamide
      (LOE 908). NSCC-1 is sensitive to LOE 908 and resistant to SK&F 96365, whereas
      NSCC-2 is sensitive to both LOE 908 and SK&F 96365. Moreover, extracellular Ca2+
      influx through these channels plays an essential role in endothelin-1-induced
      mitogenesis in C6 glioma cells. The purpose of the present study was to
      investigate the effects of extracellular Ca2+ influx on intracellular pathways of
      endothelin-1-induced mitogenic responses in C6 glioma cells. We focused on
      extracellular signal-regulated kinase 1 and 2 (ERK1/2) in this context. An
      inhibitor of mitogen-activated protein kinase, 2-[2-amino-3-methoxyphenyl]-4H-1
      benzopyran-4-one (PD 98059), abolished the endothelin-1-induced increase in
      ERK1/2 activity, but only partially suppressed the mitogenic response. ERK1/2
      activation by endothelin-1 was partially suppressed in the absence of
      extracellular Ca2+. On the basis of the sensitivity to LOE 908 and SK&F 96365,
      Ca2+ influx through NSCC-1 and NSCC-2 plays an essential role in the
      extracellular Ca2+-dependent component of ERK1/2 activity. In contrast, Ca2+
      influx through NSCC-2 is involved in the ERK1/2-independent component of
      endothelin-1-induced mitogenesis. These results indicate that (1) the endothelin
      1-induced mitogenic response involves both ERK1/2-dependent and -independent
      mechanisms, (2) ERK1/2 activation by endothelin-1 involves an extracellular Ca2+
      influx-dependent cascade as well as an extracellular Ca2+ influx-independent
      cascade, (3) because endothelin-1-induced mitogenesis is completely dependent on
      extracellular Ca2+ influx, extracellular Ca2+ influx also plays an important role
      in mitogenic pathways downstream of ERK1/2, (4) extracellular Ca2+ influx through
      NSCC-1 and NSCC-2 has an important role in the extracellular Ca2+ influx
      dependent component of ERK1/2-dependent mitogenesis, (5) extracellular Ca2+
      influx through NSCC-2 has an important role in ERK1/2-independent mitogenesis,
      and (6) Ca2+ influx through each Ca2+ channel may play a distinct role in
      intracellular mitogenic cascades.

PMID- 11821018
TI  - Molecular and pharmacological properties of inwardly rectifying K+ channels of
      human lung cancer cells.
AB  - Properties of inwardly rectifying K+ channels in small-cell lung cancer (SCLC)
      cells have not been clarified in detail. Here, we found inwardly rectifying K+
      channels in a human SCLC cell line (RERF-LC-MA), which expresses no multidrug
      resistance-associated protein 1 (MRP1) and multidrug resistance P-glycoprotein
      (MDR1). Extracellular Ba2+ and Cs+ inhibited inwardly rectifying K+ currents of
      RERF-LC-MA cells in a concentration-dependent manner, but tetraethylammonium ion
      and glibenclamide were ineffective. Okadaic acid, an inhibitor of phosphatases 1
      and 2A, and phorbol-12,13-dibutyrate, an activator of protein kinase C,
      significantly decreased the inwardly rectifying K+ current. Lowering the
      intracellular pH but not the extracellular pH decreased the K+ current. Reverse
      transcriptase-polymerase chain reaction (RT-PCR) and Western blotting analysis
      showed that RERF-LC-MA cells express Kir2.1 mRNA and protein. The inwardly
      rectifying K+ current is suggested to be generated by Kir2.1 protein in the human
      small-cell lung cancer cell, and that the K+ channel is negatively regulated by
      protein kinase C and the intracellular acidic pH.

PMID- 11821019
TI  - Potent desensitization of human P2X3 receptors by diadenosine polyphosphates.
AB  - In this study, the receptor desensitizing effects of diadenosine polyphosphates
      at recombinant human P2X3 (hP2X3) receptors were examined. Administration of
      Ap3A, Ap4A, Ap5A or Ap6A inhibited the hP2X3 receptor-mediated response to a
      subsequent application of 3 muM alphabeta-methyleneATP (alphabeta-meATP), in a
      concentration-dependent manner, with IC50 values 2707, 42, 59 and 46 nM,
      respectively. These agonists did not desensitize alphabeta-meATP responses
      mediated by the slowly desensitizing heteromeric human P2X2/3 receptor. hP2X3
      receptor desensitization was reversible and was not observed following the
      increase in intracellular Ca2+ levels produced by carbachol. A similar pattern of
      desensitization evoked by Ap5A was also observed using electrophysiological
      recordings of Xenopus oocytes expressing hP2X3 receptors. These data demonstrate
      that diadenosine polyphosphates, found endogenously in the central nervous
      system, can readily desensitize hP2X3 receptors at nanomolar concentrations that
      are 10-fold lower than are required to produce agonist-induced receptor
      activation. Thus, P2X3 receptor desensitization by diadenosine polyphosphates may
      provide an important modulatory mechanism of P2X3 receptor activation in vivo.

PMID- 11821020
TI  - PPARalpha and PPARdelta activators inhibit cytokine-induced nuclear translocation
      of NF-kappaB and expression of VCAM-1 in EAhy926 endothelial cells.
AB  - Endothelium injury is a primary event in atherogenesis, which is followed by
      monocyte infiltration, macrophage differentiation, and smooth muscle cell
      migration. Peroxisome proliferator-activated receptors (PPARs) are transcription
      factors now recognized as important mediators in the inflammatory response. The
      aim of this study was to develop a human endothelial model to evaluate anti
      inflammatory properties of PPAR activators. PPAR proteins (alpha, delta and
      gamma) are expressed in EAhy926 endothelial cells (ECs). Pirinixic acid (Wy
      14643), fenofibrate, fenofibric acid, the Merck ligand PPARdelta activator L
      165041, 15-deoxy-Delta(12,14)-prostaglandin J2, but not rosiglitazone (BRL-49653)
      inhibited the induced expression of vascular cell adhesion molecule-1 (VCAM-1),
      as measured by enzyme linked immunosorbent assay (ELISA), and monocyte binding to
      activated-EAhy926 cells. The PPARdelta activator L-165041 had the greatest
      potency to reduce cytokine-induced monocyte chemotactic protein-1 (MCP-1)
      secretion. All PPAR activators tested which impaired VCAM-1 expression reduced
      significantly nuclear p65 amount. These results show that EAhy926 endothelial
      cells are an adequate tool to substantiate and characterize inflammatory impacts
      of PPAR activators.

PMID- 11821021
TI  - Tenidap, a novel anti-inflammatory agent, is an opener of the inwardly rectifying
      K+ channel hKir2.3.
AB  - We studied the effect of a novel anti-inflammatory agent, tenidap, on a cloned
      inwardly rectifying K+ channel, hKir2.3. Tenidap (a) potently potentiated 86Rb+
      efflux through hKir2.3 channels expressed in Chinese hamster ovary cells
      (EC50=402 nM), (b) reversibly and dose-dependently increased whole-cell and macro
      patch hKir2.3 currents (maximum whole-cell current response to tenidap was 230+/
      27% of control; EC50=1.3 microM.), and (c) caused dose-dependent and Ba2+
      sensitive membrane hyperpolarizations and concurrent decreases in input
      resistance. Potentiation of hKir2.3 by tenidap was unaffected by inhibitors of
      phospholipase A2, protein kinase C, or arachidonic acid metabolic pathways. The
      action of tenidap was not intracellular. Tenidap also had little or no effect on
      currents flowing through hKir2.1, Kv1.5, and micro1 Na+ channels. Our results
      demonstrate that tenidap is a potent opener of hKir2.3 and suggest that it can
      serve as a valuable pharmacological tool for studying physiological and
      pathological processes involving Kir2.3.

PMID- 11821022
TI  - Pharmacological and endocrinological characterisation of stress-induced
      hyperthermia in singly housed mice using classical and candidate anxiolytics
      (LY314582, MPEP and NKP608).
AB  - The stress-induced hyperthermia test is a paradigm developed several years ago to
      model the expression of autonomic hyperactivity in anxiety. Whereas in the
      classical stress-induced hyperthermia, cohort removal was used, in a recently
      described modification of the stress-induced hyperthermia model singly housed
      mice rather than groups of mice were used. The modification of this model can be
      summarized as follows: rectal temperature is recorded in singly housed animals at
      two consecutive time-points (T1 and T2) which are interspaced by a defined time
      interval (15 min). Since the value at the second temperature-recording exceeds
      the value of the initial measure it is the difference between these two core
      temperatures which reflects stress-induced hyperthermia. In the present study,
      the stress-induced hyperthermia paradigm, in its modified design, was evaluated
      in OF1/IC mice. By comparing the effect of various compounds in both the modified
      as well as the classical (cohort removal) stress-induced hyperthermia paradigm, a
      very high correlation was found for the pharmacological sensitivity of the two
      paradigms. Furthermore, it was demonstrated that other anxiolytics, all known to
      be active in the classical stress-induced hyperthermia paradigm, such as the
      benzodiazepines chlordiazepoxide (0.3, 1, 3, 10 mg/kg, p.o.), diazepam (0.1, 0.3,
      1, 3 mg/kg, p.o.), clobazam (5 or 10 mg/kg, p.o.) and oxazepam (5 or 10 mg/kg,
      p.o.) as well as the non-benzodiazepines buspirone (7.5 or 15 mg/kg, p.o.) and
      ethanol (15% or 30%, 10 ml/kg, p.o.), showed a marked reduction in stress-induced
      hyperthermia in the modified design. New candidate anxiolytics, i.e. the
      metabotropic glutamate (mGlu) receptor group 2 agonist LY314582 (1 or 10 mg/kg,
      p.o.; racemic mixture of LY354740 ((2S,4S)-2-amino-4-(4,4-diphenylbut-1-yl)
      pentane-1,5-dioic acid), the metabotropic glutamate 5 receptor antagonist MPEP
      (1, 7.5, 15 or 30 mg/kg, p.o.; 2-methyl-6-(phenylethynyl)pyridine) and the
      neurokinin 1 (NK1) receptor antagonist NKP608 (0.01 or 0.1 mg/kg, p.o.; quinoline
      4-carboxylic acid [trans-(2R,4S)-1-(3,5-bis-trifluoromethyl-benzoyl)-2-(4-chloro
      benzyl)-piperidin-4-yl]-amide) also reduced stress-induced hyperthermia in the
      modified paradigm clearly indicating anxiolytic-like activity for these
      compounds. Finally, the effects of the classical benzodiazepine chlordiazepoxide
      (10 mg/kg, p.o.), in parallel with its effect on stress-induced hyperthermia,
      were also investigated for its effect on plasma concentrations of the two stress
      hormones, adrenocorticotropin (ACTH) and corticosterone. It was shown that all
      three parameters were significantly increased 15 min after T1 in vehicle-treated
      mice whereas the increase was significantly attenuated following pre-treatment
      with chlordiazepoxide. In conclusion, all the data presented here indicate that
      the modified version of the stress-induced hyperthermia-paradigm is a valid and
      interesting alternative to the classical stress-induced hyperthermia test.

PMID- 11821023
TI  - Functional diversity among 5-substituted nicotine analogs; in vitro and in vivo
      investigations.
AB  - Two 5-substituted derivatives of nicotine (nicotinic acetylcholine receptor:
      K(i)=2.4 nM) were synthesized and evaluated: 5-bromonicotine (K(i)=6.9 nM) and 5
      methoxynicotine (K(i)=14.3 nM). Despite their high affinity, neither 5
      bromonicotine nor 5-methoxynicotine mimicked nicotine in producing
      antinociceptive (tail-flick, hotplate), hypolocomotor, or hypothermic effects in
      mice. Neither agent antagonized the hypolocomotor actions of nicotine, whereas 5
      methoxynicotine, but not 5-bromonicotine, antagonized the antinociceptive (tail
      flick) activity of nicotine in a dose-related manner. In tests of stimulus
      generalization using rats trained to discriminate 0.6 mg/kg of (-)-nicotine from
      vehicle, 5-bromonicotine substituted for nicotine. Further evaluation of 5
      bromonicotine indicated that it might be a partial agonist at alpha4beta2
      receptors (stimulation of Rb(+) efflux; alpha4beta2 receptors expressed in
      oocytes) and at alpha3-containing nicotinic acetylcholine receptors (synaptosomal
      dopamine release). Thus, 5-bromonicotine might be acting as a partial agonist at
      alpha4beta2 receptors and/or some of its effects might be related to interactions
      with non-alpha4beta2 receptors. Clearly, the effects of 5-bromonicotine and 5
      methoxynicotine are different from those of nicotine, and from one another. These
      actions demonstrate that substitution at the 5-position of nicotine exerts a
      profound influence on the pharmacological profile as well as agonist/antagonist
      properties of nicotine.

PMID- 11821024
TI  - Tolerance to the neurotoxic effects of methamphetamine in young rats.
AB  - The present study examined whether exposure to methamphetamine during adolescence
      (as determined in post-natal day 40 rats) might alter its effects when used in
      young adulthood (as assessed in post-natal day 90 rats). Results confirm that
      high-dose methamphetamine administration (4x10 mg/kg/injection, s.c., 2-h
      intervals) decreases striatal dopamine uptake and transporter ligand binding in
      post-natal day 90 rats; effects that were blocked if animals received six
      biweekly methamphetamine pretreatments (15 mg/kg; s.c.) beginning at post-natal
      day 40. This neuroprotection was not likely due to pharmacokinetic tolerance,
      since brain methamphetamine concentrations did not differ 1 h after the high-dose
      methamphetamine regimen among treated rats regardless of pretreatment. The
      methamphetamine biweekly pretreatment attenuated the hyperthermia caused by the
      neurotoxic methamphetamine regimen; a phenomenon that may have contributed to the
      neuroprotection.

PMID- 11821025
TI  - Role of L-type Ca2+ channels in attenuated morphine antinociception in
      streptozotocin-diabetic rats.
AB  - The role of L-type Ca2+ channels in morphine antinociception was studied in
      streptozotocin-induced diabetic and control rats, using [3H]PN200-110 [isopropyl
      4-(2,1,3-benzoxadiazol-4-yl)-1,4-dihydro-2,6-dimethyl-5-methoxycabonylpyridine-3
      caboxylate] binding (0.005-1.0 nmol/l) and rat whole brain membranes, to
      determine if the attenuation of morphine antinociception was related to
      alterations in dihydropyridine-sensitive Ca2+ channel binding characteristics.
      The tail-flick antinociceptive effect of morphine (4 mg/kg, i.p.) was
      significantly reduced in diabetic rats in comparison to that in controls.
      Nimodipine (0.1-3 mg/kg, i.p.) did not produce antinociception but significantly
      potentiated the morphine response in control rats. Nimodipine (0.3-3 mg/kg, i.p.)
      reversed the attenuation of morphine antinociception in a dose-dependent manner
      in diabetic rats. Moreover, insulin (2 U/kg, s.c.) [correction of mu/kg] reversed
      the attenuated morphine antinociception in streptozotocin-diabetic rats. A
      significant increase in the Bmax (+41%) of [3H]PN200-110 binding was observed in
      diabetic rat brain membranes compared to that in control rats. However, there was
      no change in affinity (Kd) value of [3H]PN200-110. The reduced morphine response
      in diabetic rats, in accordance with up-regulation of dihydropyridine sites, may
      be due to an increased Ca2+ influx through L-type channels. These results suggest
      a functional role of L-type Ca2+ channels in morphine antinociception and the
      diabetic state may lead to alterations in their density.

PMID- 11821027
TI  - Uptake of dopamine by cultured monkey amniotic epithelial cells.
AB  - In this study, the ability of monkey amniotic epithelial (MAE) cells to take up
      dopamine was tested by incubating the cells in buffer containing unlabeled
      dopamine under different experimental conditions followed by assaying dopamine
      content using high performance liquid chromatography with electrochemical
      detection. Results showed the capability of MAE cells to take up dopamine in a
      time- and concentration-dependent fashion, and also this uptake is sodium
      dependent. Further, selective dopamine transporter blockers inhibited dopamine
      uptake with rank order of potency that is consistent with the pharmacology of the
      dopamine transporter. These results suggest that MAE cells may be potential model
      to study dopamine uptake and release, and to explore new drugs affecting these
      processes.

PMID- 11821026
TI  - Modification of serotonin neuron properties in mice lacking 5-HT1A receptors.
AB  - Using null mutant mice for the 5-HT1A receptor (5-HT1A-/-), extracellular
      electrophysiological recordings were first conducted to evaluate the impact of
      its genetic deletion on the firing rate of dorsal raphe 5-hydroxytryptamine (5
      HT) neurons. Experiments were also done using brain slices to assess whether any
      compensation phenomenon had taken place in key receptors known to control 5-HT
      and norepinephrine release. The mean firing rate of 5-HT neurons was nearly
      doubled in 5-HT1A-/- mice, although 65% of the neurons were firing in their
      normal range. In preloaded brain slices, the 5-HT1D/B receptor agonist
      sumatriptan equally inhibited the electrically evoked release of [3H]5-HT in
      mesencephalic slices (containing the dorsal and median raphe) from wildtype and 5
      HT1A-/- mice. The 5-HT1B receptor agonist CP 93129 (1,4-dihydro-3-(1,2,3,6
      tetrahydro-4-pyridinyl)-5H-pyrrol (3, 2-b) pyridin-5-one) and the alpha2
      adrenoceptor agonist UK14,304 (5-bromo-N-(4, 5-dihydro-1H-imidazol-2-yl)-6
      quinoxalinamine) produced the same inhibitory effect in both groups of mice in
      hippocampus and frontal cortex slices. No difference was observed on the UK14,304
      mediated inhibition of [3H]norepinephrine from preloaded slices of the two latter
      structures between the two groups of mice. In conclusion, the loss of control of
      the 5-HT1A autoreceptor in 5-HT1A-/- mice lead to a significant enhancement of 5
      HT neuronal firing, but it did not alter 5-HT or norepinephrine release in any of
      the brain structures examined. In addition, it was not associated with changes in
      the function of 5-HT1D and 5-HT1B autoreceptors and of alpha2-adrenergic
      heteroreceptors on 5-HT neurons, nor of that of alpha2-adrenoceptors on
      norepinephrine terminals.

PMID- 11821028
TI  - Evaluation of the reinforcing effects of the cannabinoid CB1 receptor antagonist,
      SR141716, in rhesus monkeys.
AB  - The abuse liability of a selective cannabinoid CB1 receptor antagonist, SR141716
      (N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H
      pyrazole-3-carboxyamide hydrochloride), was evaluated in rhesus monkeys. Four
      rhesus monkeys with chronically indwelling venous catheters were initially
      trained to self-administer cocaine (30 microg/kg/injection) during daily 1-h
      sessions under a fixed ratio 50 (FR50) schedule of reinforcement. SR141716 was
      subsequently substituted for cocaine, and SR141716 dose was varied from 1 to 100
      microg/kg/injection. Each dose of SR141716 was tested for four consecutive
      sessions and each unit dose was separated by at least three sessions of cocaine
      self-administration. Substitution of SR141716 for cocaine resulted in rapid
      extinction of lever pressing and none of the doses of SR141716 tested was self
      administered above the vehicle levels. When the highest dose of SR141716 (100
      microg/kg/injection) was evaluated, self-administration behavior was suppressed
      below vehicle levels suggesting that behaviorally active doses were evaluated.
      Since positive results in self-administration tests are generally predictive of
      abuse potential, the negative results with SR141716 suggest that this drug would
      likely have low abuse liability.

PMID- 11821029
TI  - The effect of 7-nitroindazole on the acquisition and expression of D
      methamphetamine-induced place preference in rats.
AB  - The present study investigated the role of nitric oxide (NO) in the rewarding
      effects of D-methamphetamine using 7-nitroindazole, a potent inhibitor of
      neuronal nitric oxide synthase (nNOS), as determined by the conditioned place
      preference paradigm. Male Sprague-Dawley rats treated with D-methamphetamine (1
      mg/kg) or saline every other day for 8 days (four drug and four saline sessions)
      developed marked place preference for the drug-paired side. The administration of
      7-nitroindazole (12.5-50 mg/kg) 30 min prior to the exposure to D-methamphetamine
      dose-dependently attenuated the acquisition of D-methamphetamine-induced
      conditioned place preference. In addition, when it was acutely administered 30
      min prior to the testing session of an already established D-methamphetamine
      induced conditioned place preference, 7-nitroindazole (12.5-50 mg/kg) attenuated
      the expression of this conditioned response in a dose-dependent manner, while 7
      nitroindazole (25 and 50 mg/kg) alone showed no place preference effects. These
      findings indicate that nitric oxide (NO) is involved in the rewarding properties
      of methamphetamine and suggest that selective nNOS inhibitors maybe useful in the
      management of methamphetamine abuse.

PMID- 11821030
TI  - Involvement of central K(ATP) channels in the gastric antisecretory action of
      alpha2-adrenoceptor agonists and beta-endorphin in rats.
AB  - The intracerebroventricularly (i.c.v.) injected presynaptic alpha2-adrenoceptor
      agonists, clonidine and oxymetazoline, exerted a dose-dependent inhibition on the
      gastric acid secretion in pylorus-ligated rats; the ED50 values were 20 and 7.5
      nmol/rat, respectively. Moreover, beta-endorphin, given i.c.v., also decreased
      acid secretion (ED50=0.25 nmol/rat i.c.v.). The antisecretory effect of these
      compounds was highly reduced by glibenclamide (10 nmol/rat i.c.v.), a selective
      blocker of K(ATP) channels. These results suggest that K(ATP) channels in the
      central nervous system are likely to be involved in the centrally initiated
      antisecretory action of both alpha2-adrenoceptor agonists and beta-endorphin.

PMID- 11821031
TI  - Peripheral corticotropin-releasing factor induces diarrhea in rats: role of CRF1
      receptor in fecal watery excretion.
AB  - Systemic injection of corticotropin-releasing factor (CRF) stimulates colonic
      secretory and motor functions, and CRF receptors play a role in stress-related
      alterations of colonic functions. Stress has also been reported to induce
      diarrhea and we investigated if peripheral injection of CRF can mimic this
      response in conscious rats. Intravenous (i.v.) injection of CRF (3, 10 or 30
      microg/kg) caused diarrhea in 13%, 63% and 75% of rats, respectively, and dose
      dependently increased the fecal fluid content by 5.1-, 8.6- and 10.8-fold, while
      the dried solid weight was increased by 5.2-, 4.9- and 5.8-fold, respectively,
      compared to the i.v. saline group. CRF actions were rapid in onset and blocked by
      the CRF1 receptor, antagonist CP-154,526 (butyl-[2,5-dimethyl-7-(2,4,6
      trimethylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]ethylamine). These results
      demonstrate that peripheral CRF induces watery diarrhea, primarily through the
      activation of CRF1 receptor suggesting a possible role for these pathways in
      colonic responses to stress.

PMID- 11821032
TI  - Polyglutamation of a novel antifolate, MX-68, is not necessary for its anti
      arthritic effect.
AB  - N-[[4-[(2,4-diaminopteridin-6-yl)methyl]-3,4-dihydro-2H-1,4-benzothiazin-7-yl]
      carbonyl]-L-homoglutamic acid (MX-68), a derivative of methotrexate, was
      chemically designed to resist polyglutamation and to have a high affinity for
      dihydrofolate reductase, in an attempt to reduce the side effects of
      methotrexate. We confirmed that MX-68 did not undergo polyglutamation and
      investigated the pharmacological activities of MX-68 compared with methotrexate.
      (1) In vitro: MX-68 inhibited the activity of dihydrofolate reductase to the same
      degree as methotrexate-tetraglutamate. MX-68 treatment produced a similar anti
      proliferative effect to that of methotrexate. However, the intracellular
      concentration of MX-68 was much lower than the sum of the levels of methotrexate
      and its polyglutamate, and the effects of MX-68 disappeared when it was removed
      from the culture medium. (2) In vivo: Oral administration of MX-68 suppressed the
      development of collagen-induced arthritis in mice and adjuvant-induced arthritis
      in rats, in a similar fashion to that of methotrexate. These results indicate
      that polyglutamation is not essential for the anti-arthritic effect of
      antifolates.

PMID- 11821033
TI  - Alteration in endogenous opioid systems due to chronic inflammatory pain
      conditions.
AB  - The influence of chronic arthritic pain on two endogenous opioid peptides,
      dynorphin B and [Met5]enkephalin-Arg6-Phe7, and multiple opioid receptors in
      discrete brain, lumbar spinal cord and pituitary pools was investigated. Using
      radioimmunoassay and receptor binding assay, we examined the changes in regional
      opioid peptide levels and opioid receptor activity due to chronic inflammation in
      adjuvant arthritic rats. At 4 weeks post-inoculation, increased levels of
      immunoreactive dynorphin B and [Met5]enkephalin-Arg6-Phe7 were measured in
      tissues of arthritic rats compared with controls. No significant changes in mu-,
      delta- or kappa-opioid receptors were seen after chronic inflammation. Taken
      together, these results indicate that in chronic arthritis, opioid receptor
      changes do not follow the peptide alterations of pro-dynorphin and pro-enkephalin
      systems. Thus, dynamic modification and modulation of nociceptive information
      takes place during chronic inflammation. This supports the key role of the
      central nervous system in chronic inflammatory pain conditions.

PMID- 11821034
TI  - Weekly pulse therapy of methotrexate improves survival compared with its daily
      administration in MRL/lpr mice.
AB  - The purpose of this study was to determine whether weekly pulse therapy was
      superior to daily administration of methotrexate in MRL/lpr mice. Oral
      methotrexate was given to 6-week-old MRL/lpr mice at doses of 0.3, 1.0, or 3.0
      mg/kg 5 days a week or at a dose of 15.0 mg/kg once a week until 35 weeks of age.
      The effects of methotrexate on physical, serological, and pathological findings
      were assessed. The survival rate and articular destruction on X-ray films were
      also evaluated. Both weekly pulse therapy and daily administration of
      methotrexate at the same weekly dose improved nephropathy and articular
      destruction of MRL/lpr mice when compared with control. However, weekly pulse
      therapy with methotrexate prolonged the survival of MRL/lpr mice when compared
      with the daily administration of the same weekly dose of methotrexate and
      control. Methotrexate did not suppress the increase in anti-DNA antibody and
      rheumatoid factor. Daily administration of methotrexate reduced the red and white
      blood cell counts, whereas weekly pulse therapy caused little reduction. In
      conclusion, weekly pulse therapy was superior to daily administration of
      methotrexate with respect to the survival rate, possibly due to a reduction in
      toxicity.

PMID- 11821035
TI  - Antipruritic activity of the kappa-opioid receptor agonist, TRK-820.
AB  - The effects of the kappa-opioid receptor agonist, TRK-820, (-)-17
      (cyclopropylmethyl)-3, 14beta-dihydroxy-4, 5alpha-epoxy-6beta-[N-methyl-trans-3
      (3-furyl) acrylamido] morphinan hydrochloride, on the itch sensation were
      compared with those of histamine H1 receptor antagonists, using the mouse
      pruritogen-induced scratching model. Peroral administration of TRK-820 reduced
      the numbers of substance P- or histamine-induced scratches dose dependently. No
      obvious suppression of the spontaneous locomotor activity was observed at the
      doses used for the experiments, indicating that the inhibition of scratches was
      not due to the effect on general behavior. Furthermore, the scratching inhibitory
      activity of TRK-820 was dose dependently antagonized by the specific kappa-opioid
      receptor antagonist, nor-binaltorphimine, suggesting that the inhibitory activity
      was mediated via kappa-opioid receptors. Histamine H1 receptor antagonists,
      chlorpheniramine and ketotifen, did not inhibit substance P-induced scratches, or
      did so only partially. Both antihistamines inhibited the histamine-induced
      scratches completely. These results suggest that TRK-820 has antipruritic
      activity which is mediated by kappa-opioid receptors, and is effective in both
      antihistamine-sensitive and -resistant pruritus.

PMID- 11821036
TI  - Chymase inhibitor suppresses adhesion formation in a hamster experimental model.
AB  - To clarify the role of chymase produced by mast cells in adhesion formation, we
      investigated the preventive effect of a specific chymase inhibitor, Suc-Val-Pro
      Phe(p) (OPh)2, on adhesion formation in a hamster experimental model. Hamsters
      underwent resection of the right uterine body and then 10 microM Suc-Val-Pro
      Phe(p) (OPh)2 or placebo was injected into the abdomen. Two weeks after the
      operation, the scores for adhesion formation in the chymase inhibitor-treated
      group were significantly lower than that in the placebo-treated group (placebo
      treated group, 3.60+/-0.22; chymase inhibitor-treated group, 2.10+/-0.22;
      P<0.01). This specific chymase inhibitor, Suc-Val-Pro-Phe(p) (OPh)2,
      significantly suppressed the scores for adhesion formation in a hamster
      experimental model. Thus, chymase may play an important role in the adhesion
      formation.

PMID- 11821037
TI  - Streptozotocin diabetes protects against arrhythmias in rat isolated hearts: role
      of hypothyroidism.
AB  - We examined the contribution of hypothyroidism to streptozotocin diabetes-induced
      alterations in the arrhythmia susceptibility of ex vivo hearts to regional zero
      flow ischaemia. Diabetic rats received either protamine zinc insulin (10
      IU/kg/day, s.c.) or triiodothyronine (10 microg/kg/day, s.c.) for 8 weeks
      commencing 72 h after injection of streptozotocin (60 mg/kg, i.p.). Arrhythmias
      were determined in ex vivo Langendorff-perfused hearts, subjected to a 30-min
      main left coronary artery occlusion, followed by 30-min reperfusion. Serum free
      thyroxine concentrations, rectal temperature and ex vivo heart rate were
      significantly decreased in the 8-week diabetic group (P<0.001). These changes
      were prevented by administration of triiodothyronine or insulin. Ventricular
      fibrillation during reperfusion was abolished in hearts from diabetic rats. This
      protection was prevented by treatment with either triiodothyronine or insulin.
      Hearts from methimazole-hypothyroid rats also showed no ventricular fibrillation
      during reperfusion. The protection against ischaemia-reperfusion-arrhythmias
      observed in hearts from streptozotocin-diabetic rats may be due to diabetes
      induced hypothyroidism.

PMID- 11821038
TI  - The role of 2-methyl-6-phytylbenzoquinone methyltransferase in determining
      tocopherol composition in Synechocystis sp. PCC6803.
AB  - A putative 2-methyl-6-phytylbenzoquinone (MPBQ) methyltransferase gene, SLL0418,
      was identified from the Synechocystis PCC6803 genome based on its homology to
      previously characterized gamma-tocopherol methyltransferases. Genetic and
      biochemical evidence confirmed open reading frame (ORF) SLL0418 encodes a MPBQ
      methyltransferase. An SLL0418 partial knockout mutant accumulated beta-tocopherol
      with no effect in the overall tocopherol content of the cell. In vitro assays of
      the SLL0418 gene expressed in Escherichia coli showed the enzyme efficiently
      catalyzes methylation of ring carbon 3 of MPBQ. In addition, the enzyme also
      catalyzes the methylation of ring carbon 3 of 2-methyl-6-solanylbenzoquinol in
      the terminal step of plastoquinone biosynthesis.

PMID- 11821039
TI  - Mechanism of oligomerization of Escherichia coli carbamoyl phosphate synthetase
      and modulation by the allosteric effectors. A site-directed mutagenesis study.
AB  - We use site-directed mutagenesis to clarify the role of effector-mediated
      oligomerization changes on the modulation of the activity of Escherichia coli
      carbamoyl phosphate synthetase (CPS) by its allosteric activator ornithine and
      its inhibitor UMP. The regulatory domain mutations H975L, L990A and N992A
      abolished, and N987V decreased CPS oligomerization. The oligomerization domain
      mutation L421E prevented tetramer but not dimer formation. None of the mutations
      had drastic effects on enzyme activity or changed the sensitivity or apparent
      affinity of CPS for ornithine and UMP. Our findings exclude the involvement of
      oligomerization changes in the control of CPS activity, and show that CPS dimers
      are formed by the interactions across regulatory domains, and tetramers by the
      interactions of two dimers across the oligomerization domains. A mechanism for
      effector-mediated changes of the oligomerization state is proposed.

PMID- 11821040
TI  - A strategy for the generation of non-aggregating mutants of Anthozoa fluorescent
      proteins.
AB  - Recently, we cloned several fluorescent proteins of different colors homologous
      to Aequorea victoria green fluorescent protein, which have great biotechnological
      potential as in vivo markers of gene expression. However, later investigations
      revealed severe drawbacks in the use of novel fluorescent proteins (FPs), in
      particular, the formation of tetramers (tetramerization) and high molecular
      weight aggregates (aggregation). In this report, we employ a mutagenic approach
      to resolve the problem of aggregation. The elimination of basic residues located
      near the N-termini of FPs results in the generation of non-aggregating versions
      of several FPs, specifically, drFP583 (DsRed), DsRed-Timer, ds/drFP616, zFP506,
      zFP538, amFP486, and asFP595.

PMID- 11821041
TI  - Potent transforming activity of the small GTP-binding protein Rit in NIH 3T3
      cells: evidence for a role of a p38gamma-dependent signaling pathway.
AB  - A novel branch of the Ras family, Rit, was recently identified. Rit exhibits a
      distinct C-terminus and effector domain, and does not activate mitogen-activated
      protein kinase (MAPK) but can cooperate with Raf to transform fibroblasts. Here,
      we found that when overexpressed, activated mutants of Rit transform NIH 3T3
      cells efficiently, and stimulate p38gamma but not MAPK, p38alpha, p38gamma,
      p38delta, or ERK5. Furthermore, we provide evidence that p38gamma activation is
      required for the ability of Rit to stimulate gene expression and cellular
      transformation. These findings suggest that this unique GTPase stimulates
      proliferative pathways distinct from those regulated by other Ras family members.

PMID- 11821042
TI  - Rapid oxidation of dichlorodihydrofluorescin with heme and hemoproteins:
      formation of the fluorescein is independent of the generation of reactive oxygen
      species.
AB  - Oxidative stress and the generation of reactive oxygen species (ROS) have been
      implicated in the pathogenesis of cellular damage. These events have usually been
      reported in terms of oxidation of a reporter molecule such as 2',7'
      dichlorodihydrofluorescin diacetate (DCFH-DA). Treatment of HeLa cells with hemin
      or metalloporphyrins resulted in a rapid oxidation of DCFH in a time- and dose
      dependent manner. This oxidation was inhibited by treatment of the cells with a
      large amount of superoxide dismutase and catalase, which is different from
      observations that these enzymes had no effect on the induction of heme oxygenase
      1, a stress-induced protein, in hemin-treated cells. To examine the possibility
      that the oxidation of DCFH is independent of the generation of ROS, the oxidation
      was measured using hemoglobin-synthesizing erythroleukemia K562 cells. When K562
      cells were treated with delta-aminolevulinic acid, a precursor of heme, oxidation
      of DCFH increased depending on the heme content in cells. Then DCFH-DA was
      oxidized directly with heme, hemoglobin, myoglobin and cytochrome c. These
      results suggest that oxidation of DCFH is not always related to the generation of
      ROS but may be related to heme content in cells.

PMID- 11821043
TI  - KCO1 is a component of the slow-vacuolar (SV) ion channel.
AB  - The Arabidopsis double pore K+ channel KCO1 was fused to green fluorescent
      protein and expressed in tobacco protoplasts. Microscopic analysis revealed a
      bright green fluorescence at the vacuolar membrane. RT-PCR experiments showed
      that KCO1 is expressed in the mesophyll. Vacuoles from Arabidopsis wild-type and
      kco1 knockout plants were isolated for patch-clamp analyses. Currents mediated by
      slow-activating vacuolar (SV) channels of mesophyll cell vacuoles were
      significantly smaller in kco1 plants compared to the wild-type. This shows that
      KCO1 is involved in the formation of SV channels.

PMID- 11821044
TI  - Peptide-protein interactions studied by surface plasmon and nuclear magnetic
      resonances.
AB  - The structural features of the complexes that alpha-bungarotoxin forms with three
      different synthetic peptides, mimotopes of the nicotinic acetylcholine receptor
      binding site, have been compared to the corresponding nuclear magnetic resonance
      (NMR) and surface plasmon resonance (SPR) data. For the considered peptides, the
      observed different affinities towards the toxin could not be accounted simply by
      static structural considerations. A combined analysis of the SPR- and NMR-derived
      dynamic parameters shows new correlations between complex formation and
      dissociation and the overall pattern of intramolecular and intermolecular nuclear
      Overhauser effects. These features could be crucial for a rational design of
      protein ligands.

PMID- 11821045
TI  - Expression and regulation of the nuclear receptor RORalpha in human vascular
      cells.
AB  - Retinoic acid receptor-related orphan receptor alpha (RORalpha) is a member of
      the nuclear receptor superfamily. Using RT-PCR, RORalpha mRNA was identified in
      human aortic smooth muscle cells (hASMC), endothelial cells (EC), as well as in
      human mammary arteries and atherosclerotic plaques. We found a predominant
      expression of RORalpha1 in hASMC, and RORalpha4 in EC. RORalpha2 and RORalpha3
      were not detected. In arteries, RORalpha4 was predominant compared with
      RORalpha1. In atherosclerotic plaques, RORalpha expression was significantly
      decreased. In hASMC stimulated with cytokines, RORalpha expression was increased
      by 2.5-fold. RORalpha mRNA was also significantly increased (approximately 2
      fold) in hASMC and EC cultured under hypoxia.

PMID- 11821046
TI  - A non-classical ISRE/ISGF3 pathway mediates induction of RANTES gene
      transcription by type I IFNs.
AB  - RANTES (regulated upon activation normal T cell expressed and secreted) is a
      chemoattractant cytokine important in the generation of inflammatory responses
      and human immunodeficiency virus resistance. In hematopoietic cells, RANTES is
      over-expressed by type I interferons (IFN-alpha and IFN-beta). The upstream
      region of the RANTES gene promoter contains a distal low affinity IFN-stimulated
      response element (ISRE). Specific mutagenesis in this ISRE-like motif abolished
      the activation of RANTES transcription by type I IFNs. Examination of the ISRE
      binding factors strongly suggested that signal transducer and activator of
      transcription (Stat)-2 and p48/IFN-stimulated gene factor 3gamma (ISGF3gamma) are
      not required for the induction of RANTES by type I IFNs. The specific requirement
      of Stat-1 was demonstrated using Stat-1-deficient U3A cells. These results
      revealed a non-classical ISRE/ISGF3 signal transduction pathway for the induction
      of RANTES by type I IFNs.

PMID- 11821047
TI  - The N-terminal domain of SV40 large T antigen represses the HER2/neu-mediated
      transformation and metastatic potential in breast cancers.
AB  - HER2/neu is known to be overexpressed in approximately 40% of human breast and
      ovarian cancers and it is associated with increased metastasis and poor
      prognosis. We have shown previously that the N-terminal domain of simian virus 40
      large T antigen (LT425) can act as a transforming suppressor of the HER2/neu
      oncogene in human ovarian cancer. In the present study, we demonstrate that LT425
      can also repress the transforming properties of HER2/neu-overexpressing human
      breast cancer cells. In addition, the results of a chemotaxis assay and an in
      vitro chemoinvasion assay further suggest that LT425 can also suppress the
      metastatic potential of the HER2/neu-transformed breast cancer cells. Taken
      together, these data clearly suggest that the inhibition of the expression of
      p185 HER2/neu tyrosine kinase by LT425 is capable of suppressing the HER2/neu
      mediated transformation and metastatic potential in breast cancers.

PMID- 11821048
TI  - Components required for membrane assembly of newly synthesized K+ channel KcsA.
AB  - An Escherichia coli in vitro transcription-translation system was used to study
      the components involved in the biogenesis of the homotetrameric potassium channel
      KcsA. We show that a functional signal recognition particle pathway is essential
      for tetramer formation, probably to direct correct monomer insertion in the
      membrane. In the absence of YidC or at reduced SecYEG levels, KcsA assembly
      occurs with lower efficiency. Strikingly, the highest efficiency of
      tetramerization was observed when transcription-translation was carried out in
      the presence of pure lipid vesicles, demonstrating that a phospholipid bilayer is
      the minimal membrane requirement to form the KcsA tetramer. It is concluded that
      SecYEG and YidC are not required for the formation of tetrameric KcsA in vitro.

PMID- 11821049
TI  - The role of protein nitration in the inhibition of platelet activation by
      peroxynitrite.
AB  - Peroxynitrite at low concentrations (3-10 microM) inhibited agonist-induced
      platelet aggregation by a mechanism not dependent on the formation of cyclic
      guanosine monophosphate. Platelets recovered completely from peroxynitrite
      induced inhibition within 30 min. Peroxynitrite induced nitration of cytosolic
      proteins, but this diminished to near basal levels within 60 min of exposure to
      the oxidant. During this period there was a reduction in tyrosine phosphorylation
      of specific proteins such as syk, but this was not due to direct nitration of
      these same proteins. The inhibition of phosphorylation was reversible with
      platelet proteins recovering the ability to be phosphorylated within 15 min of
      exposure to peroxynitrite. Conversely, peroxynitrite increased phosphorylation of
      other proteins, but again these events were not directly linked to nitration.
      Nitration may affect the phosphorylation of tyrosine residues in a number of
      proteins, but by an indirect route, possibly by acting on proteins upstream in
      the signalling cascades. We suggest that low concentrations of peroxynitrite
      reversibly inhibit platelet aggregation by preventing the phosphorylation of key
      signalling proteins.

PMID- 11821051
TI  - The observation of excited-state dynamical evolution in light-harvesting complex
      LH2 from Rhodobacter sphaeroides 601.
AB  - With selective excitation around BChl-B800 and BChl-B850 absorption bands, we
      observed the evolution of excited-state dynamics in LH2 from Rhodobacter
      sphaeroides 601. The dynamical traces demonstrate a dominant excited-state
      absorption (ESA) followed concomitantly by an ultrafast transmission increase and
      decay with pulse-width limited time scale at 818 nm and 828 nm excitation. The
      ESA occurring prior to excitonic thermalization or ground-state bleach was
      observed at 840 nm as well. These experimental results indicate the competition
      between the transition from excitonic states to higher-lying excited states and
      interexciton relaxation, which are of physical significance for understanding
      excitation transfer and related mechanisms in LH2.

PMID- 11821050
TI  - The integrin alphaVbeta6 binds and activates latent TGFbeta3.
AB  - Transforming growth factors-beta (TGFbeta1, 2 and 3) are secreted in a complex
      with their propeptides (latency-associated peptide 1 (LAP1), 2 and 3). TGFbeta
      signaling requires the dissociation of LAP and TGFbeta, a process termed latent
      TGFbeta activation. This process is a critical but incompletely understood step
      in the regulation of TGFbeta function. In particular, the extent to which
      activation mechanisms differ among the three TGFbeta isoforms is relatively
      unexplored. We show here that alphaVbeta6 binds and activates latent TGFbeta3.

PMID- 11821052
TI  - The unfolding mechanism and the disulfide structures of denatured lysozyme.
AB  - The mechanism of denaturation and unfolding of lysozyme has been characterized
      here using the method of disulfide scrambling. Under denaturing conditions (urea,
      guanidinium hydrochloride (GdmCl), guanidinium thiocyanate (GdmSCN), or elevated
      temperature) and in the presence of thiol initiator, lysozyme denatures by
      shuffling its four native disulfide bonds and converts to a mixture of fully
      oxidized scrambled isomers. To denature 50% of the native lysozyme requires 1.1 M
      of GdmSCN, 2.8 M of GdmCl and 7.4 M of urea, respectively. High temperature (75
      degrees C) denatures the native lysozyme quantitatively within 20 min. Analysis
      by reversed-phase high-performance liquid chromatography reveals that urea and
      GdmCl denatured lysozyme comprise a single predominant disulfide isomer,
      designated as X-lysozyme-a, regardless of the concentration of the denaturant. X
      Lysozyme-a was shown to adopt the beads-form structure with its four disulfide
      bonds formed by four consecutive pairs of cysteines (Cys6-Cys30, Cys64-Cys76,
      Cys80-Cys94, Cys115-Cys127). The conspicuous absence of partially structured
      unfolding intermediates of lysozyme contrasts to that found in the case of alpha
      lactalbumin and accounts for the widely observed two-stage mechanism of lysozyme
      unfolding.

PMID- 11821053
TI  - Mutational analysis of the apical region of domain II of the HCV IRES.
AB  - The hepatitis C virus internal ribosome entry site (IRES) binds directly to the
      40S ribosomal subunit via domains III/IV while domain II induces conformational
      changes on the ribosome which have been implicated in the decoding process. Here,
      we performed an extensive mutational study within the apical portion of domain II
      in order to address the functional role of this region on translation. Our
      results showed that the conservation of most nucleotides in this region was only
      partially related to the IRES function. Notwithstanding, however, selected single
      point mutations within the apical loop had a deleterious effect on IRES activity.

PMID- 11821054
TI  - A DMSO-sensitive conditional mutant of the fission yeast orthologue of the
      Saccharomyces cerevisiae SEC13 gene is defective in septation.
AB  - Dissection of complex processes using model organisms such as yeasts relies
      heavily upon the use of conditional mutants. We have generated a collection of
      fission yeast mutants sensitive to dimethylsulphoxide (DMSO). Among these we have
      found a mutant in the Schizosaccharomyces pombe orthologue of the Saccharomyces
      cerevisiae SEC13 gene, which fails to cleave the division septum. Generation of a
      null allele demonstrates that the S. pombe sec13 gene is essential.

PMID- 11821055
TI  - Functional properties of ryanodine receptors from rat dorsal root ganglia.
AB  - The properties of ryanodine receptors (RyRs) from rat dorsal root ganglia (DRGs)
      have been studied. The density of RyRs (Bmax) determined by [3H]ryanodine binding
      was 63 fmol/mg protein with a dissociation constant (Kd) of 1.5 nM. [3H]Ryanodine
      binding increased with caffeine, decreased with ruthenium red and tetracaine, and
      was insensitive to millimolar concentrations of Mg2+ or Ca2+. DRG RyRs
      reconstituted in planar lipid bilayers were Ca2+-dependent and displayed the
      classical long-lived subconductance state in response to ryanodine; however,
      unlike cardiac and skeletal RyRs, they lacked Ca2+-dependent inactivation.
      Antibodies against RyR3, but not against RyR1 or RyR2, detected DRG RyRs. Thus,
      DRG RyRs are immunologically related to RyR3, but their lack of divalent cation
      inhibition is unique among RyR subtypes.

PMID- 11821056
TI  - Transport of N-acetyl-D-mannosamine and N-acetyl-D-glucosamine in Escherichia
      coli K1: effect on capsular polysialic acid production.
AB  - N-Acetyl-D-mannosamine (ManNAc) and N-acetyl-D-glucosamine (GlcNAc) are the
      essential precursors of N-acetylneuraminic acid (NeuAc), the specific monomer of
      polysialic acid (PA), a bacterial pathogenic determinant. Escherichia coli K1
      uses both amino sugars as carbon sources and uptake takes place through the
      mannose phosphotransferase system transporter, a phosphoenolpyruvate-dependent
      phosphotransferase system that shows a broad range of specificity. Glucose,
      mannose, fructose, and glucosamine strongly inhibited the transport of these
      amino-acetylated sugars and GlcNAc and ManNAc strongly affected ManNAc and GlcNAc
      uptake, respectively. The ManNAc and the GlcNAc phosphorylation that occurs
      during uptake affected NeuAc synthesis in vitro. These findings account for the
      low in vivo PA production observed when E. coli K1 uses ManNAc or GlcNAc as a
      carbon source for growth.

PMID- 11821057
TI  - Conversion of L-tryptophan to serotonin and melatonin in human melanoma cells.
AB  - We showed in human melanoma cells tryptophan hydroxylase (TPH) and hydroxyindole
      methyltransferase genes expression with the sequential enzymatic activities of
      TPH, serotonin (Ser) N-acetyltransferase and hydroxyindole methyltransferase. The
      presence of the products Ser, 5OH-tryptophan, N-acetylserotonin, melatonin (Mel),
      5-methoxytryptamine and 5-methoxytryptophol was documented by liquid
      chromatography-mass spectrometry. Thus, human melanoma cells can synthesize and
      metabolize Ser and Mel.

PMID- 11821058
TI  - Inhibition of bacterial RNase P by aminoglycoside-arginine conjugates.
AB  - The potential of RNAs and RNA-protein (RNP) complexes as drug targets is
      currently being explored in various investigations. For example, a hexa-arginine
      derivative of neomycin (NeoR) and a tri-arginine derivative of gentamicin (R3G)
      were recently shown to disrupt essential RNP interactions between the trans
      activator protein (Tat) and the Tat-responsive RNA (trans-activating region) in
      the human immunodeficiency virus (HIV) and also inhibit HIV replication in cell
      culture. Based on certain structural similarities, we postulated that NeoR and
      R3G might also be effective in disrupting RNP interactions and thereby inhibiting
      bacterial RNase P, an essential RNP complex involved in tRNA maturation. Our
      results indicate that indeed both NeoR and R3G inhibit RNase P activity from
      evolutionarily divergent pathogenic bacteria and do so more effectively than they
      inhibit partially purified human RNase P activity.

PMID- 11821059
TI  - Evidence for cardiac sodium-calcium exchanger association with caveolin-3.
AB  - The interaction of cardiac Na+-Ca2+ exchange (NCX1) with caveolin proteins was
      investigated in sarcolemmal vesicles. Western blots of sarcolemmal vesicles
      revealed the presence of caveolin-1, -2, and -3. NCX1 co-fractionated more
      closely with caveolin-3 than caveolin-1 on sucrose density gradients. NCX1 has
      five possible caveolin-binding motifs and NCX1 co-precipitated specifically with
      caveolin-3. Molecular sieve column chromatography indicated that this co
      precipitation was not due to incomplete solubilization of lipid raft
      microdomains. Cholesterol chelation in vesicles decreased NCX1 transport activity
      and caveolin-3 co-precipitation. NCX1 may play a role in caveolar transmembrane
      signaling in addition to its role in excitation-contraction coupling.

PMID- 11821060
TI  - Carbonyl formation on a copper-bound prion protein fragment, PrP23-98, associated
      with its dopamine oxidase activity.
AB  - The amino-terminal part of prion protein (PrP), containing a series of
      octapeptide repeats with the consensus sequence PHGGGWGQ, has been implicated in
      the binding of copper ion. This region possesses amino acid residues susceptible
      to oxidation, such as histidine, lysine, arginine and proline. In this study, we
      have investigated copper-catalyzed oxidation of an N-terminal part of human PrP,
      PrP23-98, that was prepared by the recombinant DNA technique. Carbonyl formations
      on copper-bound PrP23-98 induced by dopamine and L-ascorbate were analyzed
      kinetically, and it was found that the redox cycling of PrP23-98-bound copper,
      especially induced by dopamine, was coupled to the formation of carbonyls on the
      protein.

PMID- 11821061
TI  - Human monocyte-derived dendritic cells are deficient in prostaglandin E2
      production.
AB  - Monocyte-derived dendritic cells (moDCs) are increasingly used in clinical
      settings to stimulate tumor immunity. Prostaglandin E2 (PGE2), which is a member
      of the eicosanoid family of oxygenated arachidonic acid derivatives generated
      through the action of cyclooxygenases (COXs), is frequently used to enhance the
      tumor necrosis factor-alpha-induced terminal maturation of moDCs. We show here
      that one effect of interleukin (IL)-4, which is used together with GM-CSF to
      generate moDCs, is the suppression of endogenous PGE2 production in moDCs. IL-4
      inhibits the cytoplasmic form of phospholipase A2, the enzyme that specifically
      liberates arachidonic acid from membrane phospholipids. Although moDCs failed to
      mobilize endogenous arachidonic acid, they converted exogenous arachidonic acid
      into PGE2 in a COX-1- and COX-2-dependent fashion. IL-4-mediated suppression of
      PGE2 biosynthesis in human moDCs explains the previously reported maturation
      enhancing effect of exogenous PGE2. The general suppression of eicosanoid
      biosynthesis may, however, limit the immunological efficacy of moDCs generated
      with IL-4.

PMID- 11821062
TI  - Molecular characterization of frog chromogranin B reveals conservation of
      selective sequences encoding potential novel regulatory peptides.
AB  - Chromogranin B (CgB) is a member of the granin family of neuroendocrine secretory
      proteins, which has been proposed to play a role in secretory granule biogenesis
      and as a precursor to bioactive peptides. The cloning of CgB in a
      phylogenetically distant vertebrate, the frog Rana ridibunda, reveals a modest
      overall homology (35-40%) with mammalian CgB. However, the sequences of the N-
      and C-terminal regions are more highly conserved (57-65% amino acid identity) and
      may give rise to novel regulatory peptides. In frog, intense expression of CgB
      mRNA was observed in particular structures of the brain and in the distal lobe of
      the pituitary.

PMID- 11821063
TI  - Lectin-like oxidized LDL receptor-1 (LOX-1) supports adhesion of mononuclear
      leukocytes and a monocyte-like cell line THP-1 cells under static and flow
      conditions.
AB  - Adhesion of mononuclear leukocytes to vascular endothelial cells appears one of
      the initial steps in the process of atherogenesis and inflammation. We examined
      if LOX-1, an endothelial scavenger receptor with C-type lectin-like structure,
      can support adhesion of mononuclear leukocytes. Under a static condition, CHO-K1
      cells stably expressing LOX-1 showed more prominent adhesion of human peripheral
      blood mononuclear leukocytes and THP-1 cells than untransfected CHO-K1 cells, in
      a temperature-independent fashion. Mononuclear leukocytes also adhered to plastic
      plates precoated with recombinant soluble LOX-1 extracellular domain. A
      neutralizing anti-LOX-1 monoclonal antibody, as well as oxidized low-density
      lipoprotein, significantly blocked adhesion of THP-1 cells to CHO-K1 cells
      overexpressing LOX-1 and bovine aortic endothelial cells. Under a flow condition,
      increased numbers of THP-1 cells showed rolling with reduced velocities on LOX-1
      expressing CHO-K1 cells, compared with those on untransfected CHO-K1 cells. Taken
      together, LOX-1 can work as a cell surface receptor for mononuclear leukocytes
      under both static and flow conditions.

PMID- 11821064
TI  - Sendai virus C protein impairs both phosphorylation and dephosphorylation
      processes of Stat1.
AB  - Sendai virus expresses C protein that blocks interferon (IFN) signaling. We
      previously reported suppression of IFN-stimulated tyrosine phosphorylation of
      signal transducers and activators of transcription (Stats) in infected cells.
      However this conclusion has remained controversial. To settle it, we re-examined
      the effect of C protein expression on phosphorylation of Stat1 in detail. IFN
      stimulated tyrosine phosphorylation of Stat1 was doubtlessly suppressed early in
      infection, but the suppression was incomplete, suggesting the importance of the
      unknown blocking mechanism that inactivates the tyrosine-phosphorylated (pY)
      Stat1 generated as the signaling leak. Interestingly, the dephosphorylation
      process of pY-Stat1 was also impaired. These effects on both phosphorylation and
      dephosphorylation processes were attributable to the function of the C protein.

PMID- 11821065
TI  - Exploring the active site of plant glutaredoxin by site-directed mutagenesis.
AB  - Six mutants (Y26A, C27S, Y29F, Y29P, C30S and Y26W/Y29P) have been engineered in
      order to explore the active site of poplar glutaredoxin (Grx) (Y26CPYC30). The
      cysteinic mutants indicate that Cys 27 is the primary nucleophile. Phe is a good
      substitute for Tyr 29, but the Y29P mutant was inactive. The Y26A mutation caused
      a moderate loss of activity. The YCPPC and WCPPC mutations did not improve the
      reactivity of Grx with the chloroplastic NADP-malate dehydrogenase, a well known
      target of thioredoxins (Trxs). The results are discussed in relation with the
      known biochemical properties of Grx and Trx.

PMID- 11821066
TI  - DNA intercalation in neutral multilamellar membranes.
AB  - We report a small angle X-ray scattering study of the DNA/neutral lipid/water
      system showing that it is possible to confine DNA into a neutral multilamellar
      phase at high lipid-to-DNA weight ratio, despite the lack of electrostatic
      interactions in this system. This phase is characterized by a 2D ordering of the
      DNA molecules intercalated between the neutral bilayers of a 3D smectic phase as
      shown from the presence of a DNA-DNA correlation peak and the 1D electron density
      profile of the multilamellar phase. We further demonstrate that it is possible to
      disperse this phase as small multilamellar vesicles encapsulating high amounts of
      DNA.

PMID- 11821067
TI  - The sorLA cytoplasmic domain interacts with GGA1 and -2 and defines minimum
      requirements for GGA binding.
AB  - We report that the Vps10p domain receptor sorLA binds the adaptor proteins GGA1
      and -2, which take part in Golgi-endosome sorting. The GGAs bind with
      differential requirements via three critical residues in the C-terminal segment
      of the sorLA cytoplasmic tail. Unlike in sortilin and the mannose 6-phosphate
      receptors, the GGA-binding segment in sorLA contains neither an acidic cluster
      nor a dileucine. Our results support the concept of sorLA as a potential sorting
      receptor and suggest that key residues in sorLA and sortilin conform to a new
      type of motif (psi-psi-X-X-phi) defining minimum requirements for GGA binding to
      cytoplasmic receptor domains.

PMID- 11821068
TI  - Charge conversion enables quantification of the proximity between a normally
      neutral mu-conotoxin (GIIIA) site and the Na+ channel pore.
AB  - mu-Conotoxin (mu-CTX) inhibits Na+ flux by obstructing the Na+ channel pore.
      Previous studies of mu-CTX have focused only on charged toxin residues, ignoring
      the neutral sites. Here we investigated the proximity between the C-terminal
      neutral alanine (A22) of mu-CTX and the Na+ channel pore by replacing it with the
      negatively charged glutamate. The analog A22E and wild-type (WT) mu-CTX exhibited
      identical nuclear magnetic resonance spectra except at the site of replacement,
      verifying that they have identical backbone structures. A22E significantly
      reduced mu-CTX affinity for WT mu1 Na+ channels (90-fold), as if the inserted
      glutamate repels the anionic pore receptor. We then looked for the interacting
      partner(s) of residue 22 by determining the potency of block of Y401K, Y401A,
      E758Q, D762K, D762A, E765K, E765A and D1241K channels by WT mu-CTX and A22E,
      followed by mutant cycle analysis to assess their individual couplings. Our
      results show that A22E interacts strongly with E765K from domain II (DII)
      (deltadeltaG=2.2 +/- 0.1 vs. <1 kcal/mol for others). We conclude that mu-CTX
      residue 22 closely associates with the DII pore in the toxin-bound channel
      complex. The approach taken may be further exploited to study the proximity of
      other neutral toxin residues with the Na+ channel pore.

PMID- 11821069
TI  - A compact view of isochores in the draft human genome sequence.
AB  - Prior to genome sequencing, information on base composition (GC level) and its
      variation in mammalian genomes could be obtained using density gradient
      ultracentrifugation. Analyses using this approach led to the conclusion that
      mammalian genomes are organized into mosaics of fairly homogeneous regions,
      called isochores. We present an initial compositional overview of the chromosomes
      of the recently available draft human genome sequence, in the form of color-coded
      moving window plots and corresponding GC level histograms. Results obtained from
      the draft human genome sequence agree well with those obtained or deduced earlier
      from CsCl experiments. The draft sequence now permits the visualization of the
      mosaic organization of the human genome at the DNA sequence level.

PMID- 11821070
TI  - Lectin-like oxidized low density lipoprotein receptor-1 (LOX-1) serves as an
      endothelial receptor for advanced glycation end products (AGE).
AB  - Advanced glycation end products (AGE) are known to serve as ligands for the
      scavenger receptors such as SR-A, CD36 and SR-BI. In the current study, we
      examined whether AGE is recognized by lectin-like oxidized low density
      lipoprotein receptor-1 (LOX-1). Cellular binding experiments revealed that AGE
      bovine serum albumin (AGE-BSA) showed the specific binding to CHO cells
      overexpressing bovine LOX-1 (BLOX-1), which was effectively suppressed by an anti
      BLOX-1 antibody. Cultured bovine aortic endothelial cells also showed the
      specific binding for AGE-BSA, which was suppressed by 67% by the anti-BLOX-1
      antibody. Thus, LOX-1 is identified as a novel endothelial receptor for AGE.

PMID- 11821071
TI  - Isochore conservation between MHC regions on human chromosome 6 and mouse
      chromosome 17.

PMID- 11821072
TI  - Strategies for the use of insulin-sensitizing drugs to treat infertility in women
      with polycystic ovary syndrome.
AB  - OBJECTIVE: Insulin resistance and its compensatory hyperinsulinemia play a key
      pathogenic role in the infertility of the polycystic ovary syndrome. Numerous
      studies indicate that insulin-sensitizing drugs can be used to enhance
      spontaneous ovulation and the induction of ovulation in the syndrome. The aim of
      this review is to summarize the studies in which insulin-sensitizing drugs were
      used to increase ovulation rate or improve fertility in women with the PCOS and
      to translate the information into practical guidelines for the use of these drugs
      by reproductive endocrinologists. DESIGN: Review and critique of studies in which
      an insulin-sensitizing drug was used to increase ovulation rate or improve
      infertility in women with the polycystic ovary syndrome. MAIN OUTCOME MEASURE(S):
      Ovulation rate and pregnancy rate. RESULT(S): Studies have demonstrated that
      insulin-sensitizing drugs can increase spontaneous ovulation, enhance the
      induction of ovulation with clomiphene citrate, and increase clinical pregnancy
      rates. CONCLUSION(S): An algorithmic approach is provided for the use of insulin
      sensitizing drugs to treat the anovulation and infertility of women with the
      polycystic ovary syndrome.

PMID- 11821073
TI  - Should employer-sponsored health insurance benefits be made public?

PMID- 11821074
TI  - Human immunodeficiency virus and infertility treatment.

PMID- 11821075
TI  - The truth is out there: a guide to the pitfalls of interpreting evidence-based
      medicine in studies of human reproduction.

PMID- 11821076
TI  - In vitro fertilization-intracytoplasmic sperm injection split: an insemination
      method to prevent fertilization failure.
AB  - OBJECTIVE: To determine whether the performance of intracytoplasmic sperm
      injection (ICSI) in cases of unexplained infertility and of borderline semen
      parameters can prevent fertilization failure. DESIGN: Prospective cohort study.
      SETTING: Hospital-based assisted reproductive technology program. PATIENT(S):
      Sixty couples with unexplained infertility (group 1) and 50 couples with
      borderline semen (group 2). INTERVENTION(S): Conventional IVF and ICSI were
      performed on sibling oocyte cumulus complexes. MAIN OUTCOME MEASURE(S): Rate of
      fertilization according to patient diagnosis. RESULT(S): The fertilization rate
      per oocyte cumulus complex in couples with unexplained infertility (group 1) was
      significantly higher with ICSI (65.3%) compared with IVF insemination (48.1%).
      Fertilization rates per OCC in couples with borderline semen (group 2) were not
      significantly different between ICSI (58.1%) and IVF (56.7%). In group 1, failure
      of fertilization after IVF insemination occurred in 10 of the 60 couples (16.7%)
      and in none with ICSI. In group 2, 2 of 50 couples (4.0%) failed fertilization by
      IVF, and 1 (2.0%) failed with ICSI. No couple in group 2 failed both IVF
      insemination and ICSI. CONCLUSION(S): In couples with unexplained infertility, a
      higher fertilization rate was achieved through ICSI compared with conventional
      IVF. No such benefit could be demonstrated for couples with borderline semen
      parameters. The use of ICSI rescued 12 of 110 cycles (10.9%) where IVF failed.
      Adoption of the ICSI-IVF insemination split in cases of unexplained infertility
      may help eliminate fertilization failures.

PMID- 11821077
TI  - Assessment of DNA fragmentation of spermatozoa that were surgically retrieved
      from men with obstructive azoospermia.
AB  - OBJECTIVE: To determine the degree of DNA fragmentation in spermatozoa of men
      with obstructive azoospermia or anejaculation compared with that of ejaculated
      spermatozoa from fertile donors. DESIGN: Observational study. SETTING; University
      Medical Center St. Radboud, Nijmegen. The Netherlands. PATIENT(S): Forty-one
      patients with obstructive azoospermia or anejaculation and 10 fertile donors.
      MAIN OUTCOME MEASURE(S): Sperm samples were obtained surgically from the
      epididymis or testis of men with azoospermia or anejeculation and by ejaculation
      in fertile patients. DNA fragmentation was analyzed in the total sample and in a
      motile fraction that was isolated as in routine ICSI procedures. DNA breaks were
      measured by using the TdT-mediated dUTP nick-end labeling assay. RESULT(S): A
      higher percentage of cells with DNA breaks was found in men with obstructive
      azoospermia or anejaculation compared with donors (mean, 18.9% vs. 6.2%). A
      significant lower degree of DNA fragmentation was observed in the motile fraction
      from patients compared with donors (0.4% vs. 0.6%). CONCLUSION(S): High
      percentages of cells with DNA damage were found in sperm samples from men with
      obstructive azoospermia or anejaculation, but a very low frequency of damage to
      the DNA was observed in the motile fraction. In an ICSI setting, the use of
      motile sperm retrieved from epididymis or testis of men with obstructive
      azoospermia does not seem to pose a higher genetic risk to the progeny than does
      use of motile ejaculated sperm.

PMID- 11821078
TI  - Use of recombinant human follicle-stimulating hormone in the treatment of male
      factor infertility.
AB  - OBJECTIVE: To evaluate the effects of treatment with recombinant human FSH (r
      hFSH) on seminal parameters and seminiferous epithelium in idiopathic patients
      with oligozoospermia with normal FSH plasma levels. DESIGN: Randomized single
      blind study. SETTING: Academic setting. PATIENT(S): Forty-five subjects with
      idiopathic oligozoospermia (sperm count <10 x 10(6)/mL) and normal FSH and
      inhibin B plasma levels. INTERVENTION(S): Three months of treatment with r-hFSH
      50 IU (15 patients) or with r-hFSH 100 IU on alternate days (15 patients) or no
      treatment (15 patients); bilateral testicular fine-needle aspiration (FNA)
      performed before and after therapy; FSH and inhibin B plasma levels evaluated
      during treatment. MAIN OUTCOME MEASURE(S): Seminal parameters; testicular
      cytological features evaluated by FNA; plasma levels of FSH, LH, T, and inhibin
      B. RESULT(S): Treatment with r-hFSH at a dose of 50 IU induced no increase in
      sperm concentration, while treatment with r-hFSH at a dose of 100 IU induced a
      significant increase in sperm concentration. In particular, in 11/15 patients a
      doubling of the pretreatment sperm concentration was observed. No significant
      increase in sperm parameters was observed in the control group. In both groups of
      patients treated with r-hFSH, the cytological analysis before treatment showed
      hypospermatogenesis. An increase in the percentage of spermatogonia and
      spermatocytes was observed only after the treatment with r-hFSH at a dose of 100
      IU. CONCLUSION(S): The findings of this study demonstrate that r-hFSH at a dose
      of 100 IU, as previously seen with highly purified FSH, increases the
      spermatogonial population and sperm production in idiopathic patients with
      oligozoospermia with normal FSH and inhibin B plasma levels and a cytological
      picture of hypospermatogenesis.

PMID- 11821079
TI  - Pharmacological concentrations of follicle-stimulating hormone and testosterone
      improve the efficacy of in vitro germ cell differentiation in men with maturation
      arrest.
AB  - OBJECTIVE: To examine whether in vitro differentiation of germ cells from men
      with maturation arrest is improved by augmenting FSH and T concentrations above
      the values effective in samples from men with normal spermatogenesis. DESIGN:
      Prospective, controlled in vitro study. SETTING: Private assisted reproduction
      centers and a university department. PATIENT(S): Men with meiotic or postmeiotic
      maturation arrest. INTERVENTION(S): Testicular spermatid extraction, in vitro
      culture of testicular biopsy samples, intraoocyte injection of elongated
      spermatids, embryo culture and transfer. MAIN OUTCOME MEASURE(S): Progression of
      in vitro germ cell differentiation, fertilization, and pregnancy outcomes with in
      vitro cultured germ cells. RESULT(S): In some cases of meiotic and postmeiotic
      maturation arrest, more advanced germ cell stages were achieved by in vitro
      culture in the presence of 500 IU/L FSH as compared with 50 IU/L FSH. The
      beneficial effect of 500 IU/L FSH was further potentiated by a simultaneous
      increase of T concentration from 1 to 10 microM. Fertilizations with germ cells
      recovered after incubation with these pharmacological hormone concentrations gave
      rise to viable embryos and the births of five healthy babies. CONCLUSION(S):
      Pharmacological concentrations of FSH and T are beneficial for in vitro
      maturation of germ cells from some men with in vivo maturation arrest.

PMID- 11821080
TI  - Effect of incubating human sperm at room temperature on capacitation-related
      events.
AB  - OBJECTIVE: To determine the effect of human sperm incubation at room temperature
      (20 degrees C) upon capacitation-related events. DESIGN: Prospective study.
      SETTING: Basic research laboratory. PATIENT(S): Semen samples were obtained from
      normozoospermic volunteers. Human follicular fluid (hFF) was collected from women
      undergoing assisted reproductive treatment. INTERVENTION(S): Spermatozoa were
      incubated for up to 18 hours at 20 degrees C and/or 37 degrees C. MAIN OUTCOME
      MEASURE(S): Protein tyrosine phosphorylation patterns, development of
      hyperactivated motility, and induction of acrosome reaction (AR) in response to
      hFF. RESULT(S): Spermatozoa incubated for 18 hours at 20 degrees C showed an
      array of tyrosine phosphorylated proteins similar to noncapacitated cells. After
      incubation at 20 degrees C, the percentage of spermatozoa displaying
      hyperactivated motility and undergoing acrosomal loss in response to hFF was
      significantly lower when compared with cells kept the same time at 37 degrees C.
      Conversely, spermatozoa incubated overnight at 37 degrees C could respond to hFF,
      either at 37 degrees C or 20 degrees C. When preincubation at 20 degrees C was
      followed by sperm exposure to 37 degrees C, capacitation-related events could be
      activated. In capacitated cells (16 hours at 37 degrees C), 2-hour incubation at
      20 degrees C led to a significant decrease in acrosome reaction inducibility,
      suggesting sperm decapacitation. CONCLUSION(S): Human sperm incubation at room
      temperature does not allow capacitation, although it does not affect hFF-induced
      acrosome reaction in capacitated cells. The blocking effect is overcome when
      spermatozoa are exposed to 37 degrees C.

PMID- 11821081
TI  - Are zinc levels in seminal plasma associated with seminal leukocytes and other
      determinants of semen quality?
AB  - OBJECTIVE: To evaluate a potential association of zinc levels with seminal
      leukocytes, the outcome of semen cultures; and semen quality and sperm
      fertilizing capacity. DESIGN: Prospective study. SETTING: Outpatient infertility
      clinic of a university hospital. PATIENT(S): Two hundred fifty-six randomly
      chosen asymptomatic males from subfertile couples. INTERVENTION(S): None. MAIN
      OUTCOME MEASURE(S): Determination of zinc in seminal plasma by flame atomic
      absorption spectroscopy. In aliquots of the same ejaculates the following tests
      were performed: immunocytochemical round cell differentiation to determine
      leukocyte counts and ratios, microbial screening, and comprehensive evaluation of
      semen quality (sperm analysis, biochemical parameters, antisperm antibody
      testing, and in vitro examination of sperm ability to penetrate cervical mucus).
      The patients underwent medical history, clinical examination, and postcoital
      testing. Subsequent fertility was determined (controlled for female infertility
      factors). RESULT(S): The concentration of zinc in seminal plasma did not
      correlate in a statistically significant way with leukocytes in semen, nor was it
      associated with bacterial colonization. There was no statistically significant
      relationship of zinc in seminal plasma or serum with semen quality parameters nor
      with local antisperm antibody testing of the IgG or IgA class. Zinc levels did
      not influence sperm capacity to penetrate cervical mucus in vitro or in vivo, and
      did not affect subsequent fertility. CONCLUSION(S): The zinc level in seminal
      fluid and serum is not associated with silent male genital tract infection
      (indicated by seminal leukocytes); nor is it related to semen cultures in
      asymptomatic individuals. The lack of association with other semen quality
      parameters indicates that the routine determination of zinc levels during
      infertility investigation is not recommended.

PMID- 11821082
TI  - Efficacy and safety of recombinant human follicle-stimulating hormone in men with
      isolated hypogonadotropic hypogonadism.
AB  - OBJECTIVE: To assess the efficacy and safety of recombinant human follicle
      stimulating hormone (rhFSH; follitropin alpha) in increasing sperm concentration
      in 26 men with severe isolated hypogonadotropic hypogonadism (IHH). DESIGN:
      Clinical and endocrine studies using an open design. SETTING: Six university
      clinical sites in three European countries. PATIENT(S): Azoospermatic patients
      aged 16 to 48 years with IHH. INTERVENTION(S): Patients received hCG for up to 6
      months before 18 months of treatment with rhFSH. Sperm count, motility, and
      morphology were assessed every 3 months. MAIN OUTCOME MEASURE(S): Achievement of
      a sperm concentration of 1.5 x 10(6)/mL. RESULT(S): Spermatogenesis was achieved
      in 15 of 19 patients who could be evaluated, 12 achieving a sperm concentration
      of > or =1.5 x 10(6)/mL. CONCLUSION(S): With hCG, rhFSH is effective in
      initiating spermatogenesis in patients with IHH, and is well tolerated.

PMID- 11821085
TI  - Diaphragmatic endometriosis: diagnosis, surgical management, and long-term
      results of treatment.
AB  - OBJECTIVE: To describe symptoms, surgical diagnosis and treatment, and long-term
      outcome of patients with symptomatic diaphragmatic endometriosis. DESIGN:
      Observational follow-up study. SETTING: American tertiary referral center for the
      surgical treatment of endometriosis. PATIENT(S): Eight patients with
      diaphragmatic endometriosis causing severe or disabling symptoms.
      INTERVENTION(S): Laparoscopic diagnosis of diaphragmatic endometriosis followed
      by upper abdominal laparotomy for full-thickness resection of the diaphragm. MAIN
      OUTCOME MEASURE(S): Reduction of several symptoms as measured on a 5-point ranked
      ordinal scale administered by a phone survey up to 7 years after surgery.
      RESULT(S): Laparoscopy from an umbilical port may identify small "sentinel
      lesions" of endometriosis on the anterior or mid diaphragm. Eight symptomatic
      patients all had significant invasive disease with dimensions up to 5 cm across
      of the posterior right diaphragm, which could not always be seen from the
      umbilical port site. All such lesions can be seen by a laparoscope placed beneath
      the right costal margin. Laparoscopic treatment of symptomatic disease is not
      rational given the posterior placement of the disease out of sight behind the
      liver and the full-thickness nature of the disease in all eight patients.
      Laparotomy with full thickness resection of the diaphragm resulted in complete
      eradication of symptoms in seven of eight patients, and good symptomatic
      reduction in one. CONCLUSION(S): Treatment of diaphragmatic endometriosis by
      laparotomy results in a high rate of symptom relief. Laparoscopic treatment of
      diaphragmatic endometriosis will result in a high rate of incomplete diagnosis
      and incomplete treatment with a high rate of continuing symptoms.

PMID- 11821084
TI  - Obesity and serum luteinizing hormone level have an independent and opposite
      effect on the serum inhibin B level in patients with polycystic ovary syndrome.
AB  - OBJECTIVE: To elucidate whether the negative effect of obesity on the serum
      inhibin B level that we previously reported is specific or not to polycystic
      ovary syndrome (PCOS) and whether it may explain the wide interindividual
      variability in serum inhibin B levels found in patients with PCOS. DESIGN:
      Prospective study. SETTING: Reproductive endocrinology unit of an academic
      medical center. PATIENT(S): One hundred thirty-four consecutive patients with
      PCOS (mean age, 27.4 +/- 4.7 years; mean body mass index [BMI], 28.3 +/- 7.6
      kg/m(2); BMI > 25, 53%) and in 78 control women (mean age, 30.1 +/- 4.1 years;
      mean BMI, 24.3 +/- 4.9; BMI > 25, 34%). INTERVENTION: Blood sampling was
      performed in the early follicular phase in patients and in control women. MAIN
      OUTCOME MEASURE(S): BMI and waist circumference (WC), serum levels of inhibin B,
      LH, FSH, E(2), androstenedione, T, fasting insulin, and leptin were assessed in
      all subjects. RESULT(S): No difference was observed in the mean inhibin B level
      between patients and controls. The BMI and WC correlated negatively with inhibin
      B in patients with PCOS and in controls, with similar regression slopes, thus
      indicating that the influence of obesity on inhibin B is not specific to PCOS. In
      addition, we found a positive relationship between serum LH and inhibin B levels
      in PCOS. There was no significant interaction between the effects of BMI and LH
      on the serum inhibin B levels by analysis of variance (ANOVA). The mean serum
      inhibin B level in patients with PCOS with high serum LH (i.e., >the 90th
      percentile of LH in controls) was significantly higher than in those patients
      with normal LH or in controls. The highest mean inhibin B level was noted in
      nonobese patients with PCOS with high LH levels (121.0 +/- 51.2 pg/mL), while
      nonobese patients with PCOS with normal LH levels and obese patients with normal
      LH or high LH levels had similar mean levels (94.5 +/- 40.0, 84.9 +/- 34 and 91.6
      +/- 51.7 pg/mL, respectively). CONCLUSION(S): We confirm that obesity has a
      negative effect on inhibin B serum level, which is not specific to PCOS. Obesity
      and excess LH, acting oppositely and independently on inhibin B production, may
      explain the discrepancies between the previous reports studying serum inhibin B
      level in patients with PCOS. Further work is required to elucidate the mechanisms
      underlying the antagonistic effects of LH and obesity on inhibin B production in
      patients with PCOS.

PMID- 11821083
TI  - Overexpression of theca-cell messenger RNA in polycystic ovary syndrome does not
      correlate with polymorphisms in the cholesterol side-chain cleavage and 17alpha
      hydroxylase/C(17-20) lyase promoters.
AB  - OBJECTIVE: To determine whether overexpression of CYP17 or CYP11A messenger
      (m)RNA in theca cells from polycystic ovaries is related to polymorphic regions
      in the gene promoters that may increase transcription. DESIGN: Case-control
      study. SETTING: Research institute. PATIENT(S): Fifty-one women with PCOS and 280
      regularly cycling controls underwent genotyping. Thecal cells were obtained from
      23 women with PCOS and 51 controls. MAIN OUTCOME MEASURE(S): Ovarian tissue was
      obtained from women with PCOS undergoing wedge resection for treatment of their
      infertility and from controls undergoing ovariectomy for indications unrelated to
      the study. Expression of mRNA in theca cells was measured by using competitive
      reverse transcriptase polymerase chain reaction. Genotype analysis for
      polymorphisms in the CYP11A and CYP17 promoters was performed by using polymerase
      chain reaction. RESULT(S): Although expression of CYP11A and CYP17 mRNA was
      higher in women with PCOS, no significant dose effects of CYP11A or CYP17 alleles
      were observed with respect to serum testosterone; follicular fluid
      androstenedione, estradiol, and androstenedione-to-estradiol ratio; or CYP11A or
      CYP17 mRNA expression. CONCLUSION(S): Overexpression of CYP17 and CYP11A mRNA in
      theca cells from polycystic ovaries is explained by polymorphic differences in
      the gene promoters.

PMID- 11821086
TI  - Increased killer inhibitory receptor KIR2DL1 expression among natural killer
      cells in women with pelvic endometriosis.
AB  - OBJECTIVE: To investigate the host immunologic response to endometriosis in terms
      of killer inhibitory receptor (KIR) expression by natural killer (NK) cells.
      DESIGN: Case-control study of immunologic markers. SETTING: University hospital.
      PATIENT(S): We compared cells from Japanese women with laparoscopically diagnosed
      endometriosis to cells from 40 women with other laparoscopic diagnoses.
      INTERVENTION(S): Peripheral venous blood sampling and laparoscopic peritoneal
      fluid collection. MAIN OUTCOME MEASURE(S): Flow cytometry was used to assess
      expression of KIR by NK cells in the cell samples. RESULT(S): The percentage of
      cells that expressed KIR2DL1 among NK (KIR2DL1(+)NK) cells in peritoneal fluid
      and peripheral blood was significantly higher in women with endometriosis than in
      controls. The proportion of KIR2DL1(+)NK cells in peripheral blood NK cells
      before and 1 month after laparoscopic surgery did not differ significantly.
      CONCLUSION(S): The proportion of KIR2DL1(+)NK cells was increased in peritoneal
      fluid and peripheral blood in women with endometriosis; this difference is
      probably related to NK cell suppression in endometriosis. This increase in
      KIR2DL1 expression by NK cells may represent a risk factor in the pathogenesis of
      endometriosis.

PMID- 11821087
TI  - Recurrence of endometriosis in women with bilateral adnexectomy (with or without
      total hysterectomy) who received hormone replacement therapy.
AB  - OBJECTIVE: To estimate the risk of recurrence after administration of hormone
      replacement therapy (HRT) among women who have had endometriosis and who
      underwent bilateral salpingo-oophorectomy (BSO). DESIGN: Prospective randomized
      trial (115 women receiving HRT and 57 not receiving HRT). SETTING; Public
      university hospital. PATIENT(S): Women with a histologic diagnosis of
      endometriosis in whom BSO was performed; 91.8% had a total hysterectomy.
      INTERVENTION(S): Periodical clinical examination, vaginal ultrasound, and CA-125
      levels; surgical evaluation and histologic study. MAIN OUTCOME MEASURE(S):
      Recurrence rate, prognostic factors, and a mean follow-up time of 45 months.
      RESULT(S): There was no recurrence among women who did not receive HRT, versus a
      3.5% rate (4 out of 115), or 0.9% per year, in women who received HRT. Two
      recurrences required abdominal surgery. There was one additional patient who
      required surgery, but the relationship to the endometriosis recurrence was
      controversial. Among women receiving HRT, the following risk factors were
      detected: peritoneal involvement > 3 cm (2.4% recurrence per year vs. 0.3%) and
      incomplete surgery (22.2% per patient vs. 1.9%). CONCLUSION(S): Patients with a
      history of endometriosis in whom total hysterectomy and bilateral salpingo
      oophorectomy have been performed have a low risk of recurrence when HRT is
      administered. In those patients, HRT is a reasonable option. However, in cases
      with peritoneal involvement > 3 cm, the recurrence rate makes HRT a controversial
      option; if HRT is indicated, it should be monitored closely.

PMID- 11821088
TI  - PROGINS receptor gene polymorphism is associated with endometriosis.
AB  - OBJECTIVE: To investigate the association between the 306-base pair insertion
      polymorphism in intron G of the progesterone receptor (PROGINS) and
      endometriosis. DESIGN: Case-control study. SETTING: Tertiary care center.
      PATIENT(S): Ninety-five white women with surgically diagnosed and histologically
      confirmed endometriosis and 107 white women without endometriosis (controls).
      INTERVENTION(S): Determination of PROGINS was performed by polymerase chain
      reaction and gel electrophoresis. MAIN OUTCOIME MEASURE(S): Frequency and
      distribution of the PROGINS allele. RESULT(S): Frequencies of the mutant allele
      T2 was 0.17 among women with endometriosis and 0.08 among controls (odds ratio,
      2.41 [CI, 1.31-4.53]). Homozygosity for allele T2 was present in 3.2% of women
      with endometriosis and 0.9% of controls. CONCLUSION(S): PROGINS appears to be
      associated with endometriosis in white persons.

PMID- 11821089
TI  - Comparison of the efficacy and safety of two formulations of micronized
      progesterone (Ellios and Utrogestan) used as luteal phase support after in vitro
      fertilization.
AB  - OBJECTIVE: To compare the efficacy and the tolerability of two different vaginal
      formulations of micronized progesterone, Ellios and Utrogestan, used for luteal
      phase support after an in vitro fertilization (IVF) cycle. DESIGN: Cohort study.
      SETTING: Fertility center in a university hospital. PATIENT(S(: One hundred
      twenty-three women who underwent IVF/intracytoplasmic sperm injection (ICSI)
      stimulated cycles from October 1998 to March 2000, who had at least six follicles
      of > or =14 mm on the day of hCG administration. INTERVENTION(S): Patients
      received Ellios pessaries (2 times 200-mg pessary/day) or Utrogestan capsules (2
      x 100-mg capsules, two times a day). Progesterone was administered from the day
      of oocyte pickup (day 0) until menses or up to 10 weeks in pregnant patients.
      MAIN OUTCOME MEASURE(S): Progesterone levels, pregnancy rate, and tolerability
      tested by patient questionnaire. RESULT(S): The progesterone levels on days 0, 9,
      16 were not statistically different between the two formulations. The pregnancy
      rate were similar in groups 1 and 2 (25.5% vs. 18.6%), whereas tolerance was
      significantly better in group 1 versus group 2 (vaginal discharge: 43% vs. 82%).
      CONCLUSION(S): The efficacy of the two formulations of progesterone is
      comparable, although the patient tolerance for Ellios is better.

PMID- 11821090
TI  - Luteal phase support.
AB  - OBJECTIVE: To develop a consensus regarding the need for luteal phase support
      during assisted reproductive technology (ART), and to establish the optimal
      compound and route of administration for this purpose. DESIGN: Review of the
      published literature on luteal phase support. PATIENT(S): Women undergoing
      assisted reproductive technologies. INTERVENTION(S): Progesterone was
      administered orally, vaginally, or by intramuscular (i.m.) injection to
      supplement the luteal phase after assisted reproductive technology (ART). MAIN
      OUTCOME MEASURE(S): Pregnancy following ART. RESULT(S); Gonadotropin releasing
      hormone (GnRH)-agonist protocols necessitate the use of luteal phase support.
      Progesterone and human chorionic gonadotrophin (hCG) have both been used for this
      purpose, with comparable outcomes. Progesterone is the product of choice,
      however, as it is associated with a lower incidence of ovarian hyperstimulation
      syndrome (OHSS). Its use is indicated up to the serum pregnancy test. Oral, i.m.,
      and vaginal progesterone preparations are available. Intramuscular and vaginal
      preparations lead to comparable rates of implantation and clinical pregnancy,
      despite higher serum progesterone levels after i.m. injection. Oral formulations
      are inferior products for luteal support. Although widely used, i.m. progesterone
      is uncomfortable and inconvenient for patients. By contrast, the vaginal
      progesterone gel (Crinone 8%) is more convenient and easier to use.
      CONCLUSION(S): Progesterone support of the luteal phase in in vitro fertilization
      (IVF) cycles is indicated, though support beyond the serum pregnancy test may not
      be needed. The pregnancy rates after vaginal and i.m. progesterone support are
      comparable, despite higher serum levels after i.m. injection. Patients prefer the
      vaginal progesterone gel.

PMID- 11821091
TI  - Cancer incidence in a cohort of infertile women who underwent in vitro
      fertilization.
AB  - OBJECTIVE: To assess whether ovarian hyperstimulation and IVF increase the risk
      for cancer. DESIGN: Historical cohort analysis. SETTING; IVF units of two medical
      centers in Israel. PATIENT(S): Five thousand twenty-six women who underwent IVF
      between 1981 and 1992. INTERVENTION(S); Cancer incidence rates were determined
      through linkage to the National Cancer Registry and were compared with expected
      rates with respect to age, sex, and place of birth. MAIN OUTCOME MEASURE(S):
      Development of cancer. RESULT(S): Twenty-seven cases of cancer were observed, and
      35.6 were expected (standardized incidence ratio, 0.76 [95% CI, 0.50-1.10]).
      Eleven cases of breast cancer were observed, whereas 15.86 were expected
      (standardized incidence ratio, 0.69 [95% CI, 0.46-1.66]). One case of ovarian
      cancer and 1 case of cervical cancer were observed, compared with 1.74 and 1.73
      cases expected, respectively. The type of infertility, number of IVF cycles, and
      treatment outcome did not significantly affect risk for cancer. CONCLUSION(S): In
      a cohort of women treated with IVF, no excess risk for cancer was noted.

PMID- 11821092
TI  - Predictors of poor ovarian response in in vitro fertilization: a prospective
      study comparing basal markers of ovarian reserve.
AB  - OBJECTIVE: To identify and quantify predictors of poor ovarian response in in
      vitro fertilization (IVF). DESIGN; Prospective study. SETTING; Tertiary fertility
      center. PATIENT(S): One hundred twenty women undergoing their first IVF cycle.
      INTERVENTION(S): Measurement of the number of antral follicles and the total
      ovarian volume by ultrasound, and of basal levels of FSH, E(2), and inhibin B on
      cycle day 3. MAIN OUTCOME MEASURE(S): Ovarian response, and clinical and ongoing
      pregnancy rates. RESULT(S); The antral follicle count was the best single
      predictor for poor ovarian response: area under the receiver operating
      characteristic curve = 0.87. Addition of basal FSH and inhibin B levels to a
      logistic model with the antral follicle count significantly improved the
      prediction of poor response; the addition of basal E(2) levels and total ovarian
      volume did not improve the prediction. To express the discriminative performance
      of this model toward poor response, a maximum area under the receiver operating
      characteristic curve of 0.92 was calculated. Poor responders had significantly
      lower clinical and ongoing pregnancy rates than did normal responders.
      CONCLUSION(S): Our data demonstrate that the antral follicle count provides
      better prognostic information on the occurrence of poor response during hormone
      stimulation for IVF than does the patient's chronological age and the currently
      used endocrine markers. However, endocrine tests remain informative. Multivariate
      models can achieve more accurate predictions of outcomes of complex events like
      ovarian response in IVF.

PMID- 11821093
TI  - Early pregnancy loss in in vitro fertilization (IVF) is a positive predictor of
      subsequent IVF success.
AB  - OBJECTIVE: To determine the significance of biochemical pregnancy losses and
      clinical spontaneous abortion (SAB) on outcomes of future IVF cycles. DESIGN:
      Retrospective cohort study. SETTING: Academic IVF program. PATIENT(S): Women with
      a history of unsuccessful IVF attempts undergoing IVF. INTERVENTION(S): None.
      MAIN OUTCOME MEASURE(S): Clinical pregnancy rate. RESULT(S): Patients with an
      early pregnancy loss had a greater ongoing clinical pregnancy rate in the
      immediate next cycle when compared with those women who had a negative pregnancy
      test (37.3% vs. 27.3%). Patients with a history of a biochemical pregnancy or a
      clinical spontaneous abortion had an ongoing clinical pregnancy rate in the next
      cycle of 38.4% and 42.3%, respectively, compared with 27.3% in women who had a
      history of a negative pregnancy test. The cumulative pregnancy rate after the
      first IVF attempt was 54.1% in patients with a previous biochemical pregnancy
      loss, 61.4% in those with a previous clinical SAB, and 46.5% in women with a
      previous negative pregnancy test. CONCLUSION(S): Women who experience an early
      pregnancy loss after IVF have a greater likelihood of success in subsequent IVF
      cycles when compared with patients who fail to conceive.

PMID- 11821094
TI  - Thrombophilia is common in women with idiopathic pregnancy loss and is associated
      with late pregnancy wastage.
AB  - OBJECTIVE: To describe the characteristics of thrombophilia in women with
      idiopathic pregnancy loss. DESIGN: Prospective observational study. SETTING:
      Tertiary referral center in a teaching academic hospital. PATIENT(S): One hundred
      forty-five patients with repeated pregnancy loss and 145 matched controls.
      INTERVENTION(S): Prospective assessment of thrombophilia in patients and
      controls. MAIN OUTCOME MEASURE(S): Prevalence of activated protein C (APC)
      resistance, protein C, protein S, and antithrombin III deficiencies,
      antiphospholipid antibodies, factor V Leiden, factor II G20210A, and MTHFR C677T
      mutations. RESULT(S): At least one thrombophilic defect was found in 66% of study
      group patients compared with 28% in control group patients. Combined
      thrombophilic defects were documented in 21% of women with pregnancy loss
      compared with 5.5% of control patients. Late pregnancy wastage occurred more
      frequently in women with thrombophilia compared with women without thrombophilia
      (160/429 [37%] vs. 39/162 [24%], respectively). APC resistance was documented in
      39% of women with pregnancy loss compared with 3% of the control patients. APC
      resistance without factor V Leiden mutation was documented in 18% of women with
      pregnancy loss compared with none of the controls. While factor V Leiden mutation
      was more common in women with pregnancy loss (25% vs. 7.6%), factor II G20210A
      and homozygosity for MTHFR C677T contributed to pregnancy loss only in the
      presence of other thrombophilia. CONCLUSION(S): Thrombophilia was found in the
      majority (66%) of women with idiopathic pregnancy loss. APC resistance with or
      without factor V Leiden mutation is the most common thrombophilic defect, and
      combined thrombophilia is a frequent finding in women with pregnancy loss.
      Thrombophilia is associated with increased frequency of late pregnancy wastage.

PMID- 11821095
TI  - High serum luteinizing hormone and testosterone concentrations do not predict
      pregnancy outcome in women with recurrent miscarriage.
AB  - OBJECTIVE: To investigate the relationship between Day 8 serum luteinizing
      hormone (LH) and testosterone (T) concentrations, and body mass index (BMI) with
      pregnancy outcome in women with recurrent miscarriage. DESIGN: Prospective
      observational study. SETTING: National recurrent miscarriage clinic. PATIENT(S):
      Three hundred forty-four women (median age 32 years; range 18-44) with a history
      of recurrent first trimester miscarriage (median 4; 3-14; <12 weeks gestation)
      who conceived spontaneously and who received no pharmacological treatment during
      pregnancy were studied. All women were antiphospholipid antibody negative and had
      a normal peripheral karyotype as did their partners. INTERVENTION(S): Outcome of
      untreated pregnancies. MAIN OUTCOME MEASURE(S): Day 8 serum LH and T
      concentrations and BMI were correlated with pregnancy outcome. RESULT(S): One
      hundred and ninety-two (55.8%) women had a live birth and 152 (44.2%) women
      miscarried. Polycystic ovarian morphology was diagnosed in 174 women (50.6%).
      There was no significant relationship between follicular phase LH concentrations
      and pregnancy outcome. Pregnancy outcome was similar in women with normal and
      high serum T concentrations. BMI value was not significantly different between
      women who had a live birth and those who miscarried. CONCLUSION(S): The analysis
      of this large cohort of women with recurrent miscarriage demonstrates that
      prepregnancy Day 8 serum LH and T concentrations, and BMI do not have a
      statistically significant relationship with pregnancy outcome.

PMID- 11821096
TI  - Coagulation factor XII activity, but not an associated common genetic
      polymorphism (46C/T),is linked to recurrent miscarriage.
AB  - OBJECTIVE: To investigate whether a factor XII genetic polymorphism is associated
      with first-trimester embryonal loss. DESIGN: Prospective case-control study.
      SETTING; Nagoya City University Hospital. PATIENT(S): Eighty-three patients with
      a history of two or more unexplained first-trimester recurrent miscarriages and
      67 controls with no obstetric complications or history of miscarriage. MAIN
      OUTCOME MEASURE(S): Plasma factor XII activity, a genetic polymorphism (46 C-->T)
      of factor XII, lupus anticoagulant, and beta(2)glycoprotein I dependent
      anticardiolipin antibodies. RESULT(S): Ten of the 83 patients and 1 of the 67
      controls had decreased factor XII activity; the difference in frequency was
      statistically significant. Wild-type (CC), heterozygote (CT), and homozygote (TT)
      allele patterns were observed in 8, 36, and 39 patients, respectively, compared
      with 11, 20, and 36 of the patients and controls, respectively. The mean (+/- SD)
      corresponding factor XII activity was 154.8 +/- 44.8%, 112.7 +/- 30.2%, and 66.2
      +/- 29.2% in patients and 164.6 +/- 26.7%, 114.3 +/- 28.1%, and 70.4 +/- 18.1% in
      controls. The two groups did not differ in the frequency of the T allele or
      categories of factor XII activity. CONCLUSION(S): Factor XII activity overall,
      but not the 46C/T common genetic polymorphism, is associated with recurrent
      miscarriage.

PMID- 11821097
TI  - Antimullerian hormone serum levels: a putative marker for ovarian aging.
AB  - OBJECTIVE: To investigate whether serum concentrations of antimullerian hormone
      may be used as a marker for ovarian aging. DESIGN: Longitudinal observational
      study. SETTING: Academic research center. PATIENTS: Forty-one normo-ovulatory
      premenopausal women and 13 healthy postmenopausal women. MAIN OUTCOME MEASURE(S):
      Concentrations of serum antimullerian hormone (assessed on two occasions 2.6 +/-
      1.7 years apart), FSH, inhibin B, and estradiol and number of ovarian follicles
      on ultrasonography. RESULT(S): Concentrations of antimullerian hormone decreased
      significantly over time (median value, 2.1 microg/L [range, 0.1-7.4 microg/L] at
      visit 1 vs. 1.3 microg/L [range, 0.0-5.0 microg/L] at visit 2), whereas the
      number of antral follicles and levels of FSH and inhibin B did not change. During
      visits 1 and 2, concentrations of antimullerian hormone correlated with age (r = 
      .40, P=.01 and r = -.57, P<.001, respectively); number of antral follicles (r
      =.66, P<.001 and r =.71, P<.001); and, to a lesser extent, with FSH level (r = 
      .29, P=.07 and r = -.37, P<.05) but not with inhibin B levels. CONCLUSION(S):
      Serum concentrations of antimullerian hormone decreased over time in young normo
      ovulatory women, whereas other markers associated with ovarian aging did not
      change. Concentrations of antimullerian hormone correlate with the number of
      antral follicles and age and less strongly with FSH level. Concentrations of
      antimullerian hormone may be a novel marker for ovarian aging.

PMID- 11821098
TI  - High serum concentrations of dimeric inhibins A and B in normal newborn girls.
AB  - OBJECTIVE: To establish the serum pattern of dimeric inhibins in normal girls
      during the newborn period and to examine its relationship with the postnatal
      gonadotropic surge. DESIGN: Retrospective study. SETTING; Division of
      endocrinology of a children's hospital. PATIENT(S): Thirty-one girls 4 to 65 days
      of age. MAIN OUTCOME MEASURE(S): Serum levels of FSH, LH, and inhibin A and B.
      RESULT(S): High serum concentrations of both dimeric inhibins were detected
      during the first weeks of life. Concentrations tended to decrease through the
      second month of age. Inhibin A and B concentrations positively correlated with
      age only during the first 2 weeks of life (r =.57, P<.05 and r =.70, P<.01,
      respectively). Inhibin A and B were positively and significantly correlated with
      LH (r =.57, P<.05 and r =.52, P<.05, respectively) and with each other (r =.68,
      P<.0001). No correlation was found between dimeric inhibins and FSH.
      CONCLUSION(S): The high inhibin concentrations observed in newborn girls, which
      indicate advanced follicular development and granulosa cell differentiation, may
      be useful markers for congenital gonadal disorders.

PMID- 11821099
TI  - Administration of an antiprogesterone up-regulates estrogen receptors in the
      endometrium of women using Norplant: a pilot study.
AB  - OBJECTIVE: To determine the effect of a single dose of mifepristone (200 mg) on
      endometrial estrogen and progesterone receptors in Norplant users. DESIGN: A
      prospective single-blind placebo-controlled pilot study. SETTING; Women were
      recruited from a large family planning clinic and were studied either at the
      clinic or in a clinical research unit attached to a teaching hospital gynecology
      department. PATIENT(S): Eight women using Norplant and experiencing vaginal
      bleeding more often than once every 24 days. All completed the study.
      INTERVENTION(S): Endometrial biopsies were taken after treatment with both
      placebo and 200 mg of mifepristone, both given at the start of a bleeding
      episode. MAIN OUTCOME MEASURE(S): Expression of endometrial progesterone (PR) and
      estrogen (ER) receptors, ovulation, and vaginal bleeding. RESULT(S): Mifepristone
      administration was associated with down-regulation of PR receptor subtype B and
      up-regulation of ER. Women treated with mifepristone showed a tendency to
      increased ovulation rates and reduced vaginal bleeding. CONCLUSION(S): The effect
      of mifepristone on endometrial steroid receptors was consistent with functional
      inhibition of progesterone. The findings warrant further investigation of this
      regimen as a strategy to reduce frequent bleeding.

PMID- 11821100
TI  - In vitro culture and in vitro maturation of mouse preantral follicles with
      recombinant gonadotropins.
AB  - OBJECTIVE: To develop an effective method for in vitro maturation of preantral
      follicles isolated from mice ovarian tissue. DESIGN: Isolated preantral follicles
      were randomly allocated to designed experimental groups for study. SETTING:
      University-based research lab. PATIENT(S): Healthy, normal mice. INTERVENTION(S):
      Superovulation with pregnant mare serum gonadotropin and hCG. MAIN OUTCOME
      MEASURE(S): Morphological changes and E(2) production were assessed. RESULT(S):
      To obtain competent oocytes, preantral follicles must be cultured with medium
      containing insulin and recombinant gonadotropins (i.e., recombinant FSH and
      recombinant LH), with a change of medium daily. A high initial recombinant LH or
      recombinant FSH facilitates E(2) secretion, enhances granulosa cell outgrowth,
      and has earlier antral formation. However, prolonged culture in high-recombinant
      LH or recombinant FSH triggers early differentiation and luteinization of
      granulosa cells, which results in low metaphase II oocyte and blastocyst
      formation. CONCLUSION(S): We have developed a culture system that allows the
      successful maturation of preantral follicles in vitro. The matured follicles are
      a physiologically functional unit that not only secrete E(2) but also generate
      competent oocytes. In a special condition, 90% of the cultured follicles
      survived, 53.5% of them produced MII oocytes, and 50% of the derived MII oocytes
      were fertilized and reached the blastocyst stage after culture in vitro.

PMID- 11821101
TI  - Factors influencing pregnancy rates with a combined clomiphene
      citrate/gonadotropin protocol for non-assisted reproductive technology fertility
      treatment.
AB  - OBJECTIVE: To determine the effectiveness of a combined clomiphene
      citrate/gonadotropin protocol in a general infertility population and to evaluate
      factors influencing pregnancy rates obtained with this protocol. DESIGN: A
      retrospective chart review. SETTING; University-based infertility clinic.
      PATIENT(S): Two hundred forty-eight patients undergoing 658 cycles of minimal
      stimulation (MS) protocol from 1996-2000. INTERVENTION(S): Patients underwent
      treatment with clomiphene citrate and gonadotropin, often followed by
      intrauterine insemination. MAIN OUTCOME MEASURE(S): Clinical pregnancy rates.
      RESULT(S): Overall, the clinical pregnancy rate was 7.1% per cycle (n = 248
      patients and 658 cycles). The age range of the patients was 24-47 years (mean +/-
      SD = 36.5 +/- 4.9) with 8.7% noted to have ovulatory dysfunction. Pregnancy rates
      varied significantly (P<.05) with patient age (9.3% in women <40 years vs. 2.4%
      in women > or =40), duration of infertility (9.0% in women with < or =3 years of
      infertility vs. 2.2% in women with >3 years of infertility) and number of
      follicles produced during stimulation (9.1% in women with > or =3 follicles vs.
      4.6% in women with <3 follicles). CONCLUSION(S): The effectiveness of the MS
      protocol in a general infertility population with a predominantly ovulatory
      status is much less than that previously reported in a younger patient population
      with a significant rate of ovulatory dysfunction. This protocol does not appear
      to lead to pregnancy rates higher than that reported for clomiphene
      citrate/intrauterine insemination (IUI) cycles. The clinical pregnancy rates
      using a minimal stimulation protocol are particularly compromised in women over
      40, those with a longer duration of infertility or those who produce few
      follicles during stimulation.

PMID- 11821102
TI  - Use of the progestin challenge test in nonhuman primates (Macaca fascicularis).
AB  - OBJECTIVE: To determine whether the progestin challenge test (PCT) would provide
      a reliable, noninvasive indicator of endometrial stimulation in nonhuman
      primates. DESIGN; Randomized, 2x2, crossover study. SETTING; Nonhuman primates
      (Macaca fascicularis) in an academic research environment. PATIENT(S): Adult,
      surgically postmenopausal, female cynomolgous macaques (n = 27) were studied.
      INTERVENTION(S): Females were randomly assigned to receive estradiol (n = 14;
      0.028 mg/kg body weight) or vehicle (n = 13) daily. All animals were administered
      two PCTs in a crossover study design using two doses (0.28 mg/kg or 0.56 mg/kg
      body weight) of medroxyprogesterone acetate (MPA). MAIN OUTCOME MEASURE(S):
      Incidence and severity of withdrawal bleeding and serum estradiol (E(2)) and
      progesterone (P(4)) levels were evaluated. RESULT(S): Estradiol treatment
      resulted in endometrial "withdrawal" bleeding in all but one instance. Females
      receiving daily doses of E(2) exhibited a significantly greater (P<.01)
      incidence, severity, and duration of withdrawal bleeding compared to control
      animals. Of the five positive responses observed in the control females, four
      occurred when the higher dose of MPA was administered. CONCLUSION(S): These
      results indicate that the PCT is a useful, noninvasive method for determining the
      presence of endometrial stimulation in nonhuman primates.

PMID- 11821103
TI  - Secretion of keratinocyte growth factor by cultured human endometrial stromal
      cells is induced through a cyclic adenosine monophosphate-dependent pathway.
AB  - OBJECTIVE: To evaluate the effects of known modulators of endometrial function on
      the production of keratinocyte growth factor by endometrial stromal cells.
      DESIGN: The effects of dibutyryl-cyclic adenosine monophosphate (db-cAMP), 12-O
      tetradecanoylphorbol 13-acetate (TPA), ethinyl estradiol-17alpha (EE), and
      medroxyprogesterone acetate (MPA) on the secretion of keratinocyte growth factor
      by endometrial stromal cells were investigated. SETTING: Research laboratory at a
      university medical school. PATIENT(S): Eleven endometrial specimens in the late
      proliferative phase. INTERVENTION(S): Endometrial stromal cells were incubated
      for 24 hours with db-cAMP, TPA, EE, or MPA. MAIN OUTCOME MEASURE(S): The
      concentration of keratinocyte growth factor in the culture media was measured
      using an ELISA. RESULT(S): Small amounts of keratinocyte growth factor were
      detected in the culture media of unstimulated endometrial stromal cells. The
      production of keratinocyte growth factor by endometrial stromal cells was
      stimulated with db-cAMP in a dose-dependent manner. The stimulatory effect of db
      cAMP was inhibited by Rp-adenosine 3',5'-cyclic monophosphothioate. None of TPA,
      EE, nor MPA affected the keratinocyte growth factor production by these cells.
      CONCLUSION(S): These results suggest that a cAMP-dependent pathway may play an
      important role in the regulation of keratinocyte growth factor production by
      endometrial stromal cells. Keratinocyte growth factor secreted by endometrial
      stromal cells may be involved in the regeneration of the endometrium during the
      normal menstrual cycle and early pregnancy.

PMID- 11821104
TI  - Heterotopic ovarian transplantation without vascular pedicle in syngeneic Lewis
      rats: long-term evaluation of effects on ovarian structure and function.
AB  - OBJECTIVE: To assess the long-term efficacy of intraperitoneal (IP) and
      subcutaneous (SC) ovarian autotransplantation in rats. DESIGN: Experimental
      animal study. SETTING: Unit of Experimental Research, Barcelona University School
      of Medicine. ANIMAL(S): Female syngeneic Lewis rats aged 14 weeks.
      INTERVENTION(S): Group A, control group undergoing ovariectomy (n = 15); group B,
      undergoing ovariectomy and IP autologous heterotopic transplant (n = 15); and
      group C, ovariectomized with SC autologous heterotopic transplant (n = 15). In
      groups B and C, five animals were killed and their ovaries removed for
      morphometric analysis at 30 days after transplantation; five additional animals
      were killed at 180 days, and the remaining five animals were killed at 360 days.
      MAIN OUTCOME MEASURE(S): Ovarian morphometric analysis and serial measurement of
      E(2) and FSH serum levels. RESULT(S); The mean number of antral follicles in the
      control group A was significantly higher than that observed in the ovarian grafts
      collected and examined 30 days after grafting in rats from groups B and C, but
      the mean granulosa cell area was significantly higher in both transplantation
      groups than in controls because of ovarian follicular hyperplasia. Histological
      examination of ovaries removed at 6 and 12 months after grafting in groups B and
      C showed increasing degrees of fibrosis, loss of primordial follicles, and the
      presence of epithelial cysts. In groups B and C, from day 30 after surgery
      onward, serum E(2) was significantly higher and FSH significantly lower,
      respectively, than in group A. E(2) and FSH patterns in groups B and C were
      similar throughout the study period. CONCLUSION(S): Heterotopic ovarian
      transplantation without vascular pedicle in rats is characterized by follicular
      hyperplasia endocrinologically functional, followed by progressive loss of
      follicles in heterotopic ovarian autografts.

PMID- 11821106
TI  - Should gamete donors be tested for spinal muscular atrophy?
AB  - OBJECTIVE: To report two cases of spinal muscular atrophy (SMA) after artificial
      insemination and to discuss why genetic screening of the disease may be justified
      in gamete donors. DESIGN: Case report. SETTING: Academic departments of genetics
      and obstetrics. PATIENT(S): A 32-year-old woman with two successive assisted
      pregnancies. INTERVENTION(S): Molecular studies of the SMN1 (survival motor
      neuron), the determining gene of the disease. MAIN OUTCOME MEASURE(S); Prenatal
      testing to detect a homozygous deletion of the SMN1 gene; carrier diagnosis by
      quantitative analysis to detect a single or double dose of exon 7 in the SMN1
      gene. RESULT(S): After a first assisted pregnancy, an SMA child with a homozygous
      deletion of the SMN1 gene was born. In the second assisted pregnancy, using sperm
      from a different donor, a fetus with a homozygous deletion of SMN1 was detected.
      Carrier status in the donor was confirmed by a single dose of SMN1 in the
      quantitative analysis. CONCLUSION(S): Genetic screening of SMA carrier status by
      quantitative analysis of the SMN1 gene should be performed in gamete donors when
      the recipient is a known carrier. Cost-benefit analysis should be made to
      consider the inclusion of the test in prospective gamete donor programs.

PMID- 11821105
TI  - Normal pregnancies and live births after autograft of frozen-thawed hemi-ovaries
      into ewes.
AB  - OBJECTIVE: To evaluate long-term outcome of autotransplantation of cryopreserved
      hemi-ovaries into ewes. DESIGN: Animal study. SETTING: University fertility
      center, Hospices Civils de Lyon; and Ecole Nationale Veterinaire de Lyon.
      PATIENT(S): Grivette ewes. INTERVENTION(S): Six hemi-ovaries from 6 ewes aged 6
      to 12 months were frozen with a slow cooling protocol using 2 M of dimethyl
      sulfoxide as cryoprotectant. After dissection of the medulla, the hemi-ovarian
      cortex was stored at -196 degrees C in liquid nitrogen. Freezing procedure was
      performed with a programmable freezer. Semiautomatic seeding was performed before
      crystallization. Four to 6 weeks after the first laparotomy, the left ovary was
      removed and the frozen-thawed hemi-ovary was sutured. MAIN OUTCOME MEASURE(S):
      Mean plasma concentrations of FSH, LH, and progesterone after autotransplantation
      of frozen-thawed hemi-ovary. Ultrasonography was done to confirm pregnancy. Blood
      samples were collected weekly to measure FSH, LH, and progesterone. After the
      first birth, the autografted ovary was removed for histologic examination.
      RESULT(S): Plasma progesterone concentration increased in a regular manner in all
      ewes except one 4 weeks after the graft. Concentrations of FSH and LH did not
      reach the menopausal level. Four pregnancies occurred, from which 6 lambs were
      born. The first delivery of a normal lamb occurred after 135 days of gestation;
      the lamb died immediately after birth. The second delivery of two normal lambs
      occurred after 130 days of gestation. A caesarean section was performed on the
      third pregnant ewe the 110th days of gestation because the ewe had a vaginal
      prolapsus. The two normal lambs and the ewe died after surgery. The fourth birth
      of a normal lamb occurred after 132 days of gestation. Histologic examination of
      the grafted frozen-thawed ovary showed a regressing corpus luteum and few
      primordial and antral follicles. CONCLUSION(S): These four pregnancies in a ewe
      model may indicate that women who undergo preservation of their ovaries before
      chemotherapy or radiotherapy can have successful pregnancy.

PMID- 11821107
TI  - Twin pregnancy after vitrification of 2-pronuclei human embryos.
AB  - OBJECTIVE: To report an ongoing twin pregnancy after transfer of embryos that
      were vitrified at the 2-pronuclei stage in a new vitrification solution. DESIGN:
      Case report. SETTING: A tertiary-care infertility clinic. PATIENT(S): A 26-year
      old infertile woman in whom two previous IVF implantations failed.
      INTERVENTION(S): Vitrification of 2-pronuclei embryos, in vitro culture for 48
      hours, and transfer into the uterus. MAIN OUTCOME MEASURE(S): Survival and
      cleavage after vitrification and achievement of clinical pregnancy. RESULT(S):
      Six zygotes were vitrified by using a three-step protocol (4% ethylene glycol for
      3 minutes, 20% ethylene glycol for 1 minute, and 38% ethylene glycol and 1.2 M
      trehalose for 0.5 minute). After 2 months of storage in a double-straw system in
      liquid nitrogen, two zygotes were warmed and cryoprotectants were removed by
      using a four-step protocol (1 M, 0.5 M, 0.25 M, and 0.125 M of trehalose). Two
      embryos were transferred after 48 hours of in vitro culture, cleaving to 5 and 6
      cells. The resulting twin pregnancy was confirmed by ultrasonography at the sixth
      week. CONCLUSION(S): Vitrification by using ethylene glycol and trehalose appears
      to be a safe, promising method for cryopreservation of human zygotes. Storage of
      vitrified zygotes in a double-straw system does not compromise their subsequent
      potential for survival and development.

PMID- 11821108
TI  - Familial oligoasthenoteratozoospermia: evidence of autosomal dominant inheritance
      with sex-limited expression.
AB  - OBJECTIVE: To report the familial occurrence of severe
      oligoasthenoteratozoospermia in a man and five male relatives related through
      their mothers. DESIGN: Case report. SETTING: University medical center.
      PATIENT(S): Six affected family members. MAIN OUTCOME MEASURE(S): Blood and semen
      samples were collected from all affected males and some of their healthy male
      relatives. Pedigree analysis and exclusion of X-linked disorder were done.
      RESULT(S): Analysis suggested that familial nonsyndromic male factor infertility
      was present. CONCLUSION(S): The family described in this report suggests the
      existence of an autosomal dominant trait of male infertility with sex-limited
      expression.

PMID- 11821109
TI  - Return of fertility after autologous stem cell transplantation.
AB  - OBJECTIVE: To study cases where bone marrow transplantation (BMT) or peripheral
      blood stem cell transplantation (PBSCT)-induced menopause was entirely reversed.
      DESIGN: Retrospective analysis. SETTING: An inpatient BMT unit and an ambulatory
      fertility center in a university hospital. PATIENT(S): Two patients with
      Hodgkin's disease and two with advanced breast carcinoma requiring stem cell
      transplantation. INTERVENTION(S): Estrogen treatment, monitoring of follicle
      stimulating hormone (FSH) and estradiol (E(2)) levels, and, ultimately,
      monitoring of pregnancy. MAIN OUTCOME MEASURE(S): Pregnancy. RESULT(S): All four
      patients established pregnancies, but two of them elected to terminate due to the
      use of tamoxifen early in pregnancy. CONCLUSION(S): Menopausal changes resulting
      from BMT may spontaneously reverse, with reestablishment of normal hormonal
      function and viable pregnancies.

PMID- 11821110
TI  - Pregnancies derived from vitrified human zygotes.

PMID- 11821111
TI  - Embryo morphology, cumulative embryo score, and outcome in an oocyte in vitro
      maturation program.

PMID- 11821112
TI  - Cross-over study of intrauterine and intracervical insemination.

PMID- 11821114
TI  - Testing for "life"--how predictable?

PMID- 11821118
TI  - Endogenous inhibitors of snake venom phospholipases A(2) in the blood plasma of
      snakes.

PMID- 11821119
TI  - Development of a protocol for determination of domoic acid in the sand crab
      (Emerita analoga): a possible new indicator species.
AB  - The aim of this study was to begin evaluating the utility of sand crabs (Emerita
      analoga) as an indicator species for the algal neurotoxin, domoic acid (DA), in
      Monterey Bay, California, USA, a site of recurrent blooms of the DA-producing
      diatom, Pseudo-nitzschia. One of the current sentinel organisms, the sea mussel
      (Mytilus californianus), has shown minimal or undetectable toxicity during some
      local bloom events. As a critical step in assuring the accuracy of DA
      determinations in E. analoga, we have developed and validated a highly efficient
      extraction protocol that yields toxin recoveries of 97+/-2.9%. We also determined
      by HPLC-UV and receptor binding assay, with confirmation by LC-MS/MS, that sand
      crabs accumulated measurable amounts of DA during toxic Pseudo-nitzschia blooms,
      while the sea mussel showed no detectable toxin. In addition, a comparison of
      inter-animal variability in DA content revealed values ranging from ca. 0.5 to 5
      microg DAg(-1) tissue and no consistent trend with size class, based on either
      animal weight or length. These data on the toxicity of individual animals will be
      useful in designing an appropriate sampling strategy for monitoring DA and,
      importantly, indicate that sand crabs do not appear to progressively
      bioaccumulate DA with age.

PMID- 11821120
TI  - Modulation of the maitotoxin response by intracellular and extracellular cations.
AB  - The aim of the present study was to characterize the role played by intracellular
      and extracellular calcium and sodium on the maitotoxin (MTX) response in Chinese
      hamster ovary (CHO) cells. The results presented here indicated that: (1) MTX
      activates calcium and sodium influx in a concentration-dependent manner; (2)
      extracellular calcium is required for the sodium influx; (3) removal of the
      extracellular sodium did not prevent the MTX-induced calcium influx; (4)
      elevation in the intracellular calcium concentration potentiates the MTX
      response; and (5) MTX, at the concentrations tested, did not compromise cell
      viability.

PMID- 11821121
TI  - Pharmacological characterization and neutralization of the venoms used in the
      production of Bothropic antivenom in Brazil.
AB  - Some pharmacological effects of the venoms of five different Brazilian Bothrops
      species and a pool of these venoms (AgB) were quantified. The ability of
      polyspecific Bothropic antivenom produced at Fundacao Ezequiel Dias (FUNED,
      Brazil) to neutralize the principal toxic and enzymatic activities was studied
      using in vivo and in vitro assays. The lethality, hemorrhagic, necrotizing,
      proteolytic, phospholipase, coagulant and fibrinolytic activities were measured
      for each of these venoms. Comparison of protein electrophoretic patterns showed
      significant differences such as the presence of common and also unique
      components. Furthermore, experimental studies revealed differences in their
      biological properties among individual samples. It was found that the Bothrops
      antivenom was highly effective in the neutralization of the toxic activities of
      all venoms tested. In addition, indirect ELISA was used to compare the antigenic
      cross-reactivity for each of the five Bothrops venoms as well as the venoms of B.
      atrox, B. leucurus and B. erythromelas which were not included in the antigenic
      pool (AgB). Therefore, the characterization of several toxic activities of snake
      venoms is necessary, if toxicity is to be properly evaluated. Results indicate
      that the Brazilian antivenom prepared at FUNED against Bothrops snakes is
      effective in neutralizing the main toxic effects of Bothrops venoms.

PMID- 11821122
TI  - Evaluation of marine biotoxin's accumulation by Acanthocardia tuberculatum from
      Algarve, Portugal.
AB  - Acanthocardia tuberculatum is a bivalve mollusc that presents recurrent problems
      of paralytic shellfish poisoning (PSP) contamination in the Mediterranean coasts
      of Spain and Morocco. Although not commercially exploited from the Portuguese
      south coast, it represents an alternative for reducing the harvest pressure on
      species presently exploited. Evaluation of accumulation of marine biotoxins was
      carried out by HPLC in this species, harvested during a campaign carried out in
      April 2001 aimed at evaluating bivalve's resources that covered the entire
      Portuguese south coast.PSP toxins were studied by automated pre-column oxidation.
      Toxins were found in specimens from all stations, but always under the regulatory
      limit of 80 microg STX eq./100g. Saxitoxin and decarbamoyl-saxitoxin were the
      only PSP toxins unambiguously identified. In commercially exploited species,
      saxitoxin and analogues were not detected. The amnesic toxin domoic acid was
      found, but in levels similar to those found in species commercially exploited,
      and always under the regulatory limit of 20 microg/g. A fast elimination, and not
      a prolonged retention, of domoic acid seems to occur in A. tuberculatum in view
      of the levels close to or higher than 20 microg/g found in commercial bivalves
      harvested the two preceding months. The diarrhoeic toxin okadaic acid was found
      at trace levels much under the allowable level, similar to what was happening
      with other species harvested during the same period.

PMID- 11821124
TI  - Asian scorpion BmK venom induces plasma extravasation and thermal hyperalgesia in
      the rat.
AB  - In the present study, the effects of scorpion Buthus martensi Karsch (BmK) venom
      on plasma extravasation and paw withdrawal latency (PWL) to radiant heat have
      been investigated in rats. BmK venom (20-200 microg/kg) by subcutaneous injection
      under the surface of the rat hindpaw causes dose-dependant increased plasma
      extravasation that could be partially inhibited by intraperitoneal (i.p.)
      injected morphine (6 mg/kg). Peak plasma extravasation was reached at 10 min and
      persisted for 60 min at a dose of 200 microg/kg. BmK venom induced cutaneous
      hyperalgesia as indicated by decreased PWL to radiant heat in the ipsilateral paw
      following subcutaneous injection of 20 microg/kg BmK venom without effect on PWL
      of the contralateral hindpaw. Meanwhile, it was found that i.p. morphine
      injection could inhibit this decreased ipsilateral PWL. The results thus suggest
      that BmK venom could induce peripheral inflammation in rat by subcutaneous
      injection, and may prove a valuable animal model for investigating the
      pathophysiology of a number of inflammatory diseases and identifying potential
      anti-inflammatory and analgesic drugs.

PMID- 11821123
TI  - Role of melittin-like region within phospholipase A(2)-activating protein in
      biological function.
AB  - Phospholipase A(2)-activating protein (PLAA) has been implicated in the
      production of prostaglandins (e.g. PGE(2)) via activation of phospholipases in
      various stimulated cell types. Human PLAA, with 738 amino acid (aa) residues,
      contains a region of 38% homology (aa 503-538) with the 26-aa long melittin
      peptide, a major component of bee venom and a reported regulator of phospholipase
      A(2) and phospholipase D activity. To learn more about the role of PLAA in the
      production of eicosanoids and other inflammatory mediators, we synthesized a
      murine PLAA peptide (36-aa long) having homology to melittin, as well as to human
      and rat PLAA. The PLAA peptide and melittin increased the expression of genes
      encoding the proinflammatory cytokine tumor necrosis factor alpha (TNFalpha) and
      cyclooxygenase-2 (COX-2), which is involved in PGE(2) production. We determined
      that the C-terminal region of the PLAA peptide (aa 515-538) was essential, since
      truncation of the C-terminal end of the PLAA peptide significantly reduced
      expression of genes encoding TNFalpha and COX-2 in macrophages. We concluded that
      PLAA could be important in the regulation of the inflammatory response because of
      its stimulatory effects on eicosanoid and cytokine synthesis. Consequently,
      control of plaa gene expression could be a target for the development of new
      drugs to control the inflammatory response.

PMID- 11821125
TI  - Involvement of specific integrins in apoptosis induced by vascular apoptosis
      inducing protein 1.
AB  - Hemorrhagic snake venom induces apoptosis in vascular endothelial cells (VEC). In
      previous reports, we described the purification and cDNA cloning from Crotalus
      atrox of vascular apoptosis-inducing protein 1 (VAP1) that specifically induces
      apoptosis in VEC. VAP1 belongs to the metalloprotease/disintegrin family. Yet the
      mechanism of inducing apoptosis by VAP1 is still not known. Since other various
      metalloproteases and disintegrins in snake venoms are known to influence
      extracellular matrix and cell adhesion, we investigated here the involvement of
      these adhesion molecules in VAP1-induced apoptosis. Consequently, VAP1 induced
      apoptosis without degrading extracellular matrix or inhibiting adhesion of VEC.
      However, VAP1-induced apoptosis was inhibited by antibodies for integrin alpha3,
      alpha6, beta1. Additionally, apoptosis was inhibited by antibody for CD9, an
      integrin associated protein. These results suggest that integrins are involved in
      VAP1-induced apoptosis by some specific role rather than that of adhesion to
      extracellular matrix.

PMID- 11821126
TI  - mRNA secondary structure can greatly affect production of recombinant
      phospholipase A(2) toxins in bacteria.
AB  - The neurotoxic activity of ammodytoxin A (AtxA), a phospholipase A(2) from Vipera
      ammodytes ammodytes venom, has been investigated by protein engineering. With the
      aim of obtaining AtxA as a non-fused protein in the bacterial cytoplasm and
      avoiding problems with incomplete cleavage in vivo of the initial Met preceding
      the first residue (Ser1), a double mutant (S1A/E4Q) was prepared and expressed in
      Escherichia coli. Immunoblotting of the bacterial lysate showed that the mutant
      was synthesized at a low level not exceeding 0.5% of total cell protein. Analysis
      of the potential secondary structure of the mutant mRNA in the translation
      initiation region suggested that the Ala1 (GCC) and Leu2 (CUG) codons used are
      likely to be involved in a hairpin structure with the Thr13 (ACG) and Gly14 (GGG)
      codons, hindering effective translation at the ribosome. To weaken this structure
      (by DeltaG of about 20 kJ/mol) the same double mutant was prepared using another
      mutagenic oligonucleotide with silent mutations in the Ala1 (GCU) and Leu2 (UUG)
      codons. The mutant was successfully produced at a level of approximately 15% of
      total protein, with the initial Met completely removed in the bacterial cell.
      Such an approach could be important in solving similar problems in bacterial
      production of other toxic proteins.

PMID- 11821127
TI  - Pathological effects of lyngbyatoxin A upon mice.
AB  - Histopathological changes induced in mice by lyngbyatoxin A were studied in
      connection with the occurrence of the toxin in marine turtles implicated in human
      intoxication. Lyngbyatoxin A showed an i.p. lethal dose 250 microg/kg in immature
      mice (3-week old) and most severely damaged capillaries of villi in the small
      intestine. Immature mice were more sensitive than matured ones and died of
      bleeding from the small intestines. With sublethal doses were observed erosion in
      the stomach, small intestine, cecum, and large intestine, as well as inflammation
      in the lung. Time course changes observed after p.o. administration of sublethal
      doses indicated severe mucus secretion and injuries to occur within 60 min in the
      intestine and within 24h in the stomach. Increased inflammatory cells followed
      these injuries. The injuries in the lung, stomach, and small intestine took a few
      weeks for recovery. The cause of death and the effective dose levels resembled
      those of aplysiatoxin poisoning.

PMID- 11821129
TI  - Properties of proteinaceous toxins in the salivary gland of the marine gastropod
      (Monoplex echo).
AB  - Three proteinaceous toxins (named echotoxins 1, 2, and 3) with both lethal and
      hemolytic activities were purified from the salivary gland of the marine
      gastropod (Monoplex echo) by gel filtration on Sephadex G-75 and cation-exchange
      FPLC on Mono S, although marked reduction in toxicity was observed in the latter
      chromatography. When subjected to reverse-phase HPLC on TSKgel Phenyl-5PW RP,
      echotoxin 2 afforded a single peak, while both echotoxins 1 and 3 were further
      separated into two components, respectively. All echotoxins are monomeric simple
      proteins with a molecular mass of about 25kDa and their N-termini are blocked.
      Amino acid compositions of echotoxins 1a, 1b, and 2 are closely similar to one
      another, being characterized by the abundance of Gly and Ala and the absence of
      half-Cys, Met, and Trp. Of the sugars, lipids and glycolipids tested,
      gangliosides potently inhibited the hemolytic activity of echotoxins.
      Furthermore, ganglioside G(T1b) inhibited both in vivo hemolysis and lethality in
      mice displayed by echotoxins. It is thus concluded that echotoxins injected into
      mice induce rapid hemolysis by binding to receptors (possibly gangliosides)
      gangliosides in the erythrocyte membrane, eventually leading to death of mice.

PMID- 11821128
TI  - Scorpion toxins from Tityus cambridgei that affect Na(+)-channels.
AB  - By means of high performance liquid chromatography (HPLC) the soluble venom of
      the Amazonian scorpion Tityus cambridgei was fractionated into over 50 different
      components. Four toxic and/or lethal peptides to mice were obtained in pure form
      and sequenced. Mass spectrometry analysis showed molecular weights of 7310, 7151,
      7259 and 7405, respectively, for toxins Tc48a, Tc49a, Tc54 and Tc49b. The N
      terminal amino acid sequence was obtained for the three first toxins mentioned,
      whereas the full primary structure was determined for Tc49b. It contains 64 amino
      acid residues, closely packed by four disulfide bridges. Sequence comparison
      analysis showed similarities around 50% with other toxins from scorpions of the
      genus Tityus of Brazil. It is lethal to mice at doses of 20 microg per 20 g
      mouse. The toxin was shown to affect the Na(+)-currents permeability of rat
      cerebellum granular cells in culture. Almost a complete elimination of current
      was observed with 100 nM toxin concentration. This effect was partially
      reversible. Furthermore, this toxin does not modify the function of the Shaker B
      K(+)-channels expressed on Sf9 cells, nor does it modify the Na(+)-channel
      function in a similar manner as those reported for the alpha-scorpion toxins
      purified from other scorpions.

PMID- 11821130
TI  - Cytotoxic responses to unfractionated extracts from digestive glands of mussels.
AB  - The contamination of bivalve molluscs by lipophylic toxins is mainly detected by
      the use of unfractionated extracts from contaminated material in mouse bioassays.
      The development of alternate detection methods based on the use of cultured cells
      is hampered by difficulties related to the complexity of matrices including toxic
      compounds obtained from contaminated material. In this paper we have used
      unfractionated lipid extracts prepared from the digestive gland of mussels, which
      gave a negative response by the mouse bioassay, and have investigated their
      effects on functioning of MCF-7 cells. We show that altered growth was induced
      after addition of lipid extracts corresponding to less than 1mg of digestive
      gland per ml of culture medium. The cytotoxic effect was also confirmed by the
      analysis of the effect of the unfractionated extracts on four selected proteins,
      which were used as markers of general (actin), regulatory (mitogen activated
      protein kinase isoforms ERK1 and ERK2), as well as differentiative (alpha isoform
      of estrogen receptor) functions of the MCF-7 human breast cancer cell line.

PMID- 11821132
TI  - Evaluation of the diagnostic value of plasma copper levels in cattle.
AB  - Copper (Cu) is an essential trace element. Depletion of liver-Cu stores leads to
      clinical or sub-clinical Cu deficiency. Our objective was to evaluate plasma-Cu
      levels as a diagnostic test for the assessment of Cu status in cattle. We used
      liver-Cu levels as the gold standard. The chosen cutoff for plasma Cu was 9
      mmol/l; two different cutoffs were chosen for liver-Cu: 20 and 10 microg/g dry
      matter (DM). When 20 microg/g DM of liver Cu was the cutoff, plasma Cu had
      sensitivity=69% (58, 79) and specificity=84% (74, 93). The same values if the
      cutoff in liver was 10 microg/g were 92 (82, 100) and 73% (64, 82), respectively.
      ROC curves showed that the best cutoff to be used for plasma Cu was 8.26 mmol/l;
      however, no significant improvement was found in sensitivity or specificity. We
      concluded that interpretation of plasma-Cu levels significantly varies with the
      liver-Cu cutoff.

PMID- 11821133
TI  - Differences and similarities among experts' opinions on Salmonella enterica
      dynamics in swine pre-harvest.
AB  - A workshop was conducted to elicit expert opinion on infection status and
      transmission of salmonella in pigs at the farm of origin, during transport and
      during lairage. A second objective was to compare opinions regarding risk factors
      for salmonella introduction and control at the farm level between experts from
      different countries. Thirty-six experts from 11 countries filled in a paper-and
      pencil questionnaire during an international conference. Experts from all
      countries agreed on the risk of salmonella introduction related to live animals
      and the importance of general hygiene and all-in/all-out management for
      salmonella control. However, workshop participants from Denmark put more weight
      on factors related to feed while experts from USA rated factors related to
      rodents and people contact higher. The experts believed that 21-33% of pigs
      coming from a chronically infected farm would be infected with salmonella, but
      only one-third of the infected pigs would be shedders. Regarding transport and
      lairage, the US participants believed that contamination was occurring in the
      majority of pigs regardless of initial infection status and particularly during
      lairage; in contrast, the Danish experts were more optimistic with respect to the
      contamination and infection risk. US experts believed that the incidence of
      salmonella shedding would be high among pigs infected during transport and
      lairage and that an important proportion of 'carrier' pigs would start shedding.
      Our results reflect the differences in the level of salmonella infection and
      implemented control strategies between countries as well as the different
      philosophies that professionals have. The differences in opinion regarding
      salmonella dynamics could be due either to true differences in risk as a
      consequence of distinct management and transport practices in Denmark and USA or
      to a difference in perception.

PMID- 11821134
TI  - Seasonal epidemiology of ticks and aspects of cowdriosis in N'Dama village cattle
      in the Central Guinea savannah of Cote d'Ivoire.
AB  - In the Central Guinea savannah of Cote d'Ivoire, cattle breeding started only
      approximately 30 years ago. The impact of parasitism on the overall health status
      and productivity of the trypanotolerant N'Dama cattle in this area is unknown. In
      close collaboration with national veterinary institutions and local farmers, we
      studied spectrum, burden and seasonal dynamics of ticks (including aspects of
      cowdriosis) on N'Dama village cattle. In a longitudinal study, three randomly
      selected cattle herds (traditional farming type) of one village were examined
      repeatedly for ticks. Spectrum, burden, seasonal epidemiology of ticks were
      assessed. In these traditional herds (which lack (ecto)parasite management), all
      animals were infested by ticks at monthly counts. Five different tick species
      were identified; the four genera in order of frequency were: Amblyomma (overall
      prevalence 96%), Boophilus (47%), Hyalomma (<1%) and Rhipicephalus (<1%).
      Amblyomma variegatum was the most-abundant tick on cattle in all seasons.
      Seroprevalence of Cowdria ruminantium was 31% (95% CI: 26, 36%). Most of the
      animals typically carried low tick burdens. N'Dama cattle seem well adapted to
      their environment and can resist the tick burdens under this traditional farming
      system.

PMID- 11821135
TI  - Herd-level diagnosis for Salmonella enterica subsp. enterica serovar Dublin
      infection in bovine dairy herds.
AB  - Herd-level sensitivities of bacteriological and serological methods were compared
      in 79 bovine dairy herds, recently infected with Salmonella enterica subsp.
      enterica serovar Dublin. All farms experienced clinical signs of salmonellosis
      for the first time and had no history of vaccination against salmonellosis. At
      the start of the study, infection with serovar Dublin was confirmed with at least
      one positive bacteriologic culture for serovar Dublin from a clinical case (gold
      standard for herd infection). Bacteriological culture was done on samples of dung
      pits, drinking water, bulk-milk filters, and faeces of animals with current or
      earlier clinical signs of salmonellosis. Blood samples of all animals and bulk
      milk samples were tested using an ELISA.Herd-level sensitivity (HSe) of culture
      of dung-pits, drinking water, bulk-milk filters, and faeces of animals with
      current or earlier signs of salmonellosis was 45, 5, 7, and 38%, respectively.
      HSe for serology of all animals was 100%. If blood samples of all calves 4-6
      months old were examined, at least one calf was seropositive on 91% of the
      infected farms. If serology was performed on samples of animals with current or
      earlier signs of salmonellosis, at least one animal was seropositive on 80% of
      the infected farms. HSe for bulk-milk samples was 54%. However, if clinical signs
      of salmonellosis were observed only in lactating animals, sensitivity of bulk
      milk serology was 79%. Interesting combinations of methods were the combination
      of serology of bulk milk with either serology of animals with current or earlier
      signs of salmonellosis (HSe=91%), or serology of all calves of 4-6 months old
      (HSe=99%).

PMID- 11821136
TI  - Risk of clinical mastitis in dairy herds with a high proportion of low individual
      milk somatic-cell counts.
AB  - The relationships between the herd-somatic-cell count (SCC) pattern on a test day
      and the incidence of clinical mastitis in the subsequent period were studied by
      collecting health data and monthly records from 2 years (1995-1997) from 121
      farms located in the west of France. A total of 980 herd-periods (from one test
      day to the following one) were analyzed. The outcome variable was the incidence
      density of clinical mastitis (ICM) within the herd-period. The herd-SCC pattern
      on a test day was described by cross-combining the proportions of cows with low
      SCC (<50,000 cells/ml) or with high SCC (>250,000 cells/ml). The relationship
      between herd-SCC pattern and subsequent ICM was assessed using a generalized
      linear mixed model. A sensitivity analysis evaluated the effect of different
      proportions of cows with low SCC on significance and magnitude of the
      relationship. Risk of clinical mastitis was expressed as a risk ratio (RR) in
      comparison to a moderate herd-SCC level (with low proportions of cows with low or
      high SCC). Median ICM was 0.38 cases per 365 cow-days at risk (first and third
      quartiles: 0 and 0.88). In the situations where few cows (<15%) had SCC>250,000
      cells/ml, ICM was higher (RR>1.31) when the proportion of cows with low SCC
      exceeded 50% than in the reference situation. Risk ratios increased as the
      proportion of cows with low SCC increased from 40 to 60%. In the situations where
      the proportion of cows with SCC>250,000 cells/ml exceeded 15%, ICM was higher
      compared to the reference situation (whatever the proportion of low SCC). Risk
      ratios were also higher when the proportion of cows with low SCC were >40-60%,
      compared to the pattern with the proportion of cows with low SCC below 40%. Herd
      situations with a high proportion of cows with low SCC appeared to be at
      increased risk of clinical mastitis.

PMID- 11821137
TI  - Risk factors for L. monocytogenes contamination of dairy products in Switzerland,
      1990-1999.
AB  - Our purpose was to identify the main hazards associated with the spread of
      Listeria monocytogenes in dairy products in Switzerland and to determine the
      changes in predominant serotypes of the isolates, using databases on dairy
      processing and environments from the Swiss Dairy Research Station during the
      years 1990-1999. Overall, of 76,271 samples collected, 3722 (4.9%) were positive
      for the presence of L. monocytogenes. Cheese-ripening facilities had the highest
      proportion of positive samples (7.6%), followed by small-scale local dairies
      (4.4%). By sample type, the highest proportion of positive samples (9.5%) was
      observed in water samples used for cheese-washing, followed by cheese-surface
      swabs (5.0%). During the 10-year period, no positive samples were obtained from
      cream, ice cream, milk powder, yogurt, or fresh cheese. Of 3722 L. monocytogenes
      isolates, 1328 (35.7%) were serologically typeable. Serotypes 1/2a, 1/2b, and 4b
      accounted for 92.7% of the 1328 isolates. Until 1995, the most-prevalent serotype
      was 1/2b (annual proportional prevalence 39.3-72.2%)--whereas since 1996, 1/2a
      was the most prevalent (34.7-54.7%). During 1996-1999, serotype 1/2a increased by
      88%, compared to the average of 1990-1995. In the final random-effect
      multivariable logistic model, the strongest predictor of a positive culture was
      samples from cheese-ripening plant (OR=1.54; 95% CI: 1.14, 2.08) and the second
      strongest predictor was samples collected by someone who was employed by the
      plant (OR=1.48; 1.29, 1.71). Hard and semi-hard cheeses were more likely to be
      associated with serotype 1/2b and soft cheeses with serotype 1/2a.

PMID- 11821138
TI  - "TAGS", a program for the evaluation of test accuracy in the absence of a gold
      standard.
AB  - When a perfect reference test (i.e. "gold standard") is not available, it is
      possible to obtain estimates of test sensitivity and specificity using "latent
      class" methods. However, there are few widely available software programs that
      allow implementation of these procedures. We describe the development of a
      program (implemented in R and S-Plus software) for this purpose that yields
      maximum-likelihood estimates of sensitivity, specificity and prevalence. We also
      have implemented an HTML form, which submits data to a web-based interface to R.
      The programs can incorporate data obtained from several populations, results of
      multiple tests, and can account for data obtained from a reference population in
      which the true status (infected or non-infected) of each individual is known
      exactly. Two estimation methods are used: a Newton-Raphson procedure and an
      expectation-maximisation (EM) procedure. The estimation methods assume test
      independence conditional on the infection status of the individuals and constant
      test accuracy in each population. A goodness-of-fit statistic and the residuals
      of pairwise correlation coefficients are calculated to check the validity of
      these assumptions. Two examples are used to illustrate application and
      limitations of the programs. The programs are available at
      www.afssa.fr/interne/tags.htm (Europe) or www.epi.ucdavis.edu/diagnostictests/
      (USA).

PMID- 11821140
TI  - Influence of arrival weight, season and calf supplier on survival in Holstein
      beef calves on a calf ranch in California, USA.
AB  - On a yearly basis, large calf ranches rear thousands of neonatal cattle for
      replacement heifers, veal or dairy beef. Dairy beef ranches obtain bull-calves
      from multiple sources and with questionable colostrum intake histories. Such
      ranches accumulate large amounts of data that could be used to help them with
      calf purchasing and on-farm management practices to avoid losses. Our purpose was
      to describe some calf purchase factors associated with mortality in neonatal
      calves raised on a single large calf ranch. Computerized records describing
      120,197 bull-calves purchased between January 1997 and November 1998 were used in
      a survival analysis. Risk factors for mortality within the first 4 weeks after
      arrival on the ranch included body weight on arrival, month of arrival, and the
      calf supplier. The strength of the effects was conditional on the week after
      arrival to the ranch.

PMID- 11821139
TI  - Risk factors for infection of sow herds with porcine reproductive and respiratory
      syndrome (PRRS) virus.
AB  - In 1992, the porcine reproductive and respiratory syndrome virus (PRRSV) of
      European type (PRRSV-EU) was introduced in Denmark. By 1996, the virus had spread
      to approximately 25% of the Danish herds. In January 1996, a modified-live
      vaccine based on the American type of the virus (PRRSV-US) was used in
      replacement boars for Danish artificial insemination (AI) centres and from July
      1996, the vaccine was used in PRRSV-EU infected herds for prevention of disease.
      Soon after vaccine introduction, PRRSV non-infected herds experienced outbreaks
      of disease due to infection with PRRSV-US. In this study, we investigated the
      risk factors (biosecurity level, animals, exposure from PRRSV-US-infected
      neighbour herds, semen, herd size, pig density and herd density) for infection
      with PRRSV-US in a cohort of 1071 sow herds; we used a nested case-control study.
      The retrospective observation period lasted from June 1996 (when they all were
      non-infected) to October 1997. Seventy-three non-vaccinated, closed sow herds
      became infected with the vaccine strain during this period. Each case herd was
      matched with two control herds from the cohort (controls had not been infected at
      the time of infection in the case herds). The data were analysed using a Cox
      regression model. The hazard of infection increased significantly with exposure
      from PRRSV-US-infected neighbouring herds, purchase of animals from herds
      incubating PRRSV-US infection, increasing herd size and purchase of semen from
      boars at PRRSV-US-infected AI centres. The results are consistent with the
      modified-live vaccine strain spread to other herds by trade with animals and
      semen and by neighbour (area) transmission. We suggest that virus spread by
      aerosols was a frequent mode of transmission.

PMID- 11821141
TI  - Problems and solutions with the design and execution of an epidemiological study
      of white spot disease in black tiger shrimp (Penaeus monodon) in Vietnam.
AB  - White spot disease (WSD) is caused by white spot syndrome virus (WSSV) and is an
      acutely fatal pandemic disease of crustaceans. It has resulted in massive losses
      to the shrimp-farming industry in Asia and has now spread to the Americas. This
      paper reports the problems and solutions associated with the design and execution
      of a longitudinal epidemiological study of shrimp (Penaeus monodon) health on
      farms practising a crop rotation of rice and shrimp in the Mekong Delta of
      Vietnam. The pre-sampling phase of the project involved selecting an appropriate
      site and sampling variables, obtaining permission and establishing the necessary
      laboratory and logistic facilities. At the start of the sampling phase, 40
      farmers were selected and 32 of these were visited and interviewed. This resulted
      in the enrolment of only 17 farmers. A further seven had to be enrolled to obtain
      the maximum number of farmers that could be sampled by the study team. Compliance
      was enhanced through meetings, regular visits by senior members of the project
      team and ensuring that visits were punctual and that all information was treated
      confidentially. The production cycle began in January 1998 and lasted for
      approximately 5 months. An attempt was made to collect 500 post larvae (PL)
      before each pond was stocked to assess the health of the batch and to test for
      the presence of WSSV by one-step PCR. After stocking, the wild crustaceans also
      were sampled from the pond for PCR analyses. Information was collected on the
      management practices and samples of water, pond bottom, feed and shrimp collected
      throughout the production cycle. Water quality variables with predictable diurnal
      variation were sampled in the morning and afternoon, twice a week. Two months
      after stocking, the first outbreak of WSD occurred; subsequently, 18 farms
      conducted a complete emergency harvest due to the actual or perceived presence of
      a WSD outbreak. Detectable mortalities were reported from 19 farms, and moribund
      shrimps were collected from four of these for PCR and histological analyses.

PMID- 11821142
TI  - The new classification system for slaughter-pig herds in the Danish Salmonella
      surveillance-and-control program.
AB  - The Danish surveillance-and-control program for Salmonella in slaughter pigs was
      introduced in 1995. The key element of the program is a quick and correct
      identification of herds with high seroprevalence. After 5 years, the
      classification scheme was evaluated--and a revision was made. Data from two
      Salmonella screenings including a total of 1902 slaughter pig herds were used.
      For each herd, information was available on Salmonella status based on both
      microbiology and serology. Based on analyses of these data, suitable changes in
      the scheme were identified and their effect estimated by use of data from the
      Danish Salmonella Database including all herds in 2000. The classification scheme
      has been adjusted on the following points. (1) The sampling has been simplified
      into 60, 75, or 100 samples per herd per year depending on herd size. This means
      more-precise estimates for the seroprevalence among smaller herds. (2) Herds with
      an annual kill <or=200 finishers will not form part of the surveillance; this
      leaves 1.6% of the slaughter pigs outside the surveillance scheme. (3) The cut
      off for individual meat-juice samples has been reduced from OD% 40 to OD% 20-
      doubling the number of positive samples. (4) The results of the previous 3
      months' serological samples will be weighed 0.6:0.2:0.2 (the immediate month
      counting three times as much as the previous months), and the weighed average is
      called the "serological Salmonella index" for slaughter pig herds. A herd with an
      increasing seroprevalence will be assigned to a higher Salmonella level more
      quickly under the new scheme. (5) A herd will be assigned monthly to one of three
      levels. The limit between Levels 1 and 2 has been set to >or=index 40, and the
      limit between Levels 2 and 3 to >or=index 70. If the Danish swine producers are
      interested, a Level 0 may be introduced (consisting of seronegative herds as an
      indication of a negligible Salmonella prevalence). The classification scheme was
      introduced in August 2001.

PMID- 11821143
TI  - Factors associated with mortality in Norwegian broiler flocks.
AB  - Our aim in this longitudinal study (covering years from 1996 to 1999) was to use
      data regularly recorded in a production database, to identify farm- and flock
      level factors associated with cumulative mortality in broiler flocks during: (a)
      the 1st week after housing and (b) the rest of the growout (2nd to 5th week). A
      total of 1664 broiler flocks kept in 132 broiler farms were included. The average
      weekly cumulative mortality was 1.54% (95% CI: 1.46, 1.62%) during the 1st week
      and 0.48% (95% CI: 0.47, 0.49%) during the rest of the growout. The final least
      squares regression model of cumulative mortality during the 1st week identified
      the following significant factors: study year, flock size, stocking density, use
      of paper underlay for feeding during the 1st week, and the interaction terms
      between type of ventilation, drinking system and floor insulation. The final
      model for the 2nd to 5th week demonstrated that the factors age of the broiler
      house, heating system and control system for the air intake were associated with
      cumulative mortality, but the effects of the two latter variables were
      significantly modified by age of the broiler house. A significant difference in
      mortality between flocks delivered from various hatcheries was found in both
      analyses. Our results suggest that changes in several housing factors and
      management routines might reduce the mortality losses, but the relationship
      depends on the stage of production.

PMID- 11821144
TI  - Kinetic analysis of [35S]dATP alpha S interaction with P2y(1) nucleotide
      receptor.
AB  - The kinetics of 2'-deoxyadenosine-5'-O-(1-thiotriphosphate) ([(35)S]dATP alpha S)
      interaction with membrane fragments of transfected astrocytoma 1321N1 cells,
      expressing human P2Y(1) receptors, and the same wild-type cells, not expressing
      P2Y receptors were studied. Binding of this radioligand was observed with both
      types of membranes, but sites showing slow on-rate were found only on the
      transfected cells. These "slow" binding sites behaved as a kinetically
      homogeneous population and their interaction with the radioligand was shown to
      occur in two steps, R+A(K(A))<==>RA(k(i))<==>(k(-i))(RA), including the
      relatively slow isomerization of the complex RA into (RA). Evidence was obtained
      to assign the isomerized ("slow") binding sites on the transfected cells as
      P2Y(1) receptor sites, differentiated from other binding sites of non-receptor
      origin by kinetic analysis, and characterised by the kinetic parameters K(A)=59
      +/- 19 nM, k(i)=(9.0 +/- 0.8)10(-3)s(-1) and k(-i)=(3.9 +/- 0.7)10(-3)s(-1).
      [(35)S]dATP alpha S binding, with kinetic criteria, can be of value for
      differentiation of the receptor sites from non-receptor sites and thus provides
      solid basis for radioligand assay of P2Y(1) receptors.

PMID- 11821145
TI  - Does extracellular calcium determine what pool of GABA is the target for alpha
      latrotoxin?
AB  - Presynaptic neurotoxin alpha-latrotoxin, from the venom of Latrodectus mactans
      tredecimguttatus, causes massive [(3)H]GABA release from rat brain synaptosomes,
      irrespective of calcium presence in the extracellular medium. Whether the binding
      of alpha-latrotoxin to Ca(2+)-dependent (neurexin 1 alpha) or to Ca(2+)
      independent (latrophilin) receptor triggers [(3)H]GABA release by the same
      mechanisms or different ones, inducing either exocytotic process or outflow by
      mobile membrane GABA transporter, is unknown. We examined alpha-latrotoxin-evoked
      [(3)H]GABA release from synaptosomes which cytosolic [(3)H]GABA pool was depleted
      either by applying competitive inhibitors of the GABA transporter, nipecotic acid
      and 2,4-diaminobutyric acid, or by permeation with digitonin. We also compared
      the effect of the GABA transporter inhibitors on depolarisation-evoked and alpha
      latrotoxin-evoked [(3)H]GABA release using as depolarising agents 4-aminopyridine
      and high KCl in the Ca(2+)-containing and in Ca(2+)-free medium, respectively.
      Incubation of synaptosomes with nipecotic acid induced the essential acceleration
      of unstimulated [(3)H]GABA release and deep inhibition of high KCl-evoked Ca(2+)
      independent [(3)H]GABA release. In contrast, at the similar conditions the effect
      of alpha-latrotoxin was greatly augmented with respect to the control response.
      Another way to assay what GABA pool was involved in alpha-latrotoxin-induced
      release lays in an analysis of the effects of depolarisation and alpha-latrotoxin
      in consecutive order. The preliminary 4-aminopyridine-stimulated [(3)H]GABA
      release attenuated the toxin effect. But when depolarisation occurred in Ca(2+)
      free medium, no influence on alpha-latrotoxin effect was revealed. Employing
      digitonin-permeated synaptosomes, we have shown that alpha-latrotoxin could
      stimulate [3H]GABA release in the medium with 1mM EGTA, this effect of the toxin
      was blocked by concanavalin A and was ATP-dependent. The latter suggests that
      alpha-latrotoxin-released neurotransmitter has the vesicular nature. We assume
      that the type of the toxin membrane receptor does not determine the mechanisms of
      [(3)H]GABA release evoked by alpha-latrotoxin.

PMID- 11821146
TI  - Insulin-like growth factor-1 increases activity and surface levels of the GLAST
      subtype of glutamate transporter.
AB  - Glutamate uptake systems are the primary mechanisms involved in excitatory amino
      acids clearance, their regulation is extremely important for proper neuronal
      function. Using cultured chick cerebellar Bergmann glia cells, the involvement of
      receptor tyrosine kinases in glutamate uptake was studied. Treatment of the cells
      with insulin-like growth factor-1 but not epidermal growth factor or neuronal
      growth factor, induces a dose and time dependent increase in [(3)H]-D-aspartate
      uptake that is sensitive to wortmannin, an inhibitor of phosphatidylinositol 3
      kinase. Saturation experiments show a significant increase in V(max), suggesting
      that the amount of transporter molecules at the cell membrane under insulin-like
      growth factor-1 treatment is augmented. This interpretation was strengthen by
      equilibrium-binding experiments and by the fact that the increase in [(3)H]-D
      aspartate uptake was not dependent on protein synthesis. The present studies
      suggest that insulin-like growth factor-1 signaling is involved in modulation of
      glutamate transporter cell surface expression.

PMID- 11821147
TI  - Tamoxifen protects clonal mouse hippocampal (HT-22) cells against neurotoxins
      induced cell death.
AB  - In the present work using an established clonal mouse hippocampal (HT-22) cell
      line, we have examined whether the estrogen antagonist tamoxifen antagonizes the
      observed neuroprotective effects of estrogen against glutamate and amyloid beta
      protein neurotoxicity. Results obtained suggest that like estrogen, tamoxifen
      protects HT-22 cells against both 5mM glutamate and 2 microM amyloid beta protein
      induced cell death in a concentration dependent manner. Optimum protection was
      obtained at 500 nM tamoxifen. Tamoxifen was found to offer more potent protection
      at this dose against amyloid beta protein induced neurotoxicity when compared
      with glutamate neurotoxicity. We were unable to detect either estrogen receptor
      (ER)--ER alpha or ER beta presence in HT-22 cells using western blot technique.
      However, amyloid beta protein treatment significantly increases total
      glucocorticoid receptors (GRs) as determined by western blot technique, while
      prior treatment with estrogen or tamoxifen followed by amyloid beta protein
      resulted in the reduction of total GRs to the levels comparable to that observed
      for the control untreated cells. In addition, using confocal immunoflourescence
      microscopy technique, we observed that 20 h of treatment with 2 microM amyloid
      beta protein resulted in enhanced nuclear localization of GRs in HT-22 cells as
      compared to control untreated cells or 500 nM tamoxifen alone treated cells.
      Interestingly, 500 nM tamoxifen treatments for 24h, followed by 20 h treatment
      with 2 microM amyloid beta protein resulted in dramatic reduction in GRs nuclear
      localization. In conclusion, tamoxifen (i) protects HT-22 cells against amyloid
      beta protein neurotoxicity and (ii) neuroprotective effect is independent of ERs.

PMID- 11821148
TI  - The pentylenetetrazole-kindling model of epilepsy in SAMP8 mice: behavior and
      metabolism.
AB  - This work describes a novel epilepsy model, combining pentylenetetrazole (PTZ)
      kindling with the senescence-accelerated mouse P8 (SAMP8) a model for aging. The
      2- and 8-month-old SAMP8 mice were treated with PTZ, phenobarbital plus PTZ or
      saline every 48 h during a period of 40 days. Both 2- and 8-month-old PTZ-kindled
      mice showed a behavioral pattern that was very similar to severe chronic epilepsy
      with secondary generalized seizures. Two out of six 8-month-old animals died in
      the PTZ group. Interestingly, atypical absence seizures were limited to the 8
      month-old PTZ group. Furthermore, 8-month-old mice were more sensitive to the
      sedative effect of phenobarbital. The concentrations of several amino acids were
      examined by HPLC. Lower levels of amino acids were found in the 8-month-old
      compared to the 2-month-old control animals. No biochemical changes were observed
      between the groups of 2-month-old animals, while in the 8-month-old animals both
      treatment groups showed significantly higher concentrations of GABA, glutamine
      and glutathione. Thus, it could be shown that cerebral metabolism of 8-month-old
      SAMP8 mice was more sensitive to PTZ and phenobarbital than metabolism of 2-month
      old mice. Furthermore, it is suggested that glutamate metabolism in brains of 8
      month-old SAMP8 mice is altered and that excessive glutamate is transformed, in
      considerable amounts, into glutamate related metabolites, possibly in astrocytes.

PMID- 11821149
TI  - The non-competitive AMPA receptor antagonist (GYKI 52466) blocks quisqualate
      induced acetylcholine release from the rat hippocampus and striatum: an in vivo
      microdialysis study.
AB  - The effects of the non-N-methyl-D-aspartate (NMDA) agonist quisqualate (QUIS) and
      selective AMPA/kainate receptor antagonist 1-(aminophenyl)-methyl-7, 8
      methyilendioxy-5H-2,3-benzodiazepine (GYKI 52466) on the release of acetylcholine
      (ACh) from the hippocampus and striatum of freely moving rats were studied by
      transversal microdialysis. Acetylcholine level in the dialisate was measured by
      the high performance liquid chromatography (HPLC) method with an electrochemical
      detector. The QUIS (100 microM) perfused through the striatum induced an increase
      of extracellular ACh level (250%) which lasted for over 1h and gradually returned
      to basal values. Local perfusion of GYKI 52466 (10-100 microM) to the striatum
      did not change the basal release of ACh. GYKI 52466 (10 microM) administered
      together with QUIS (100 microM) in he striatum antagonized the stimulant effect
      of QUIS on the ACh release. Local administration of the QUIS (100 microM) through
      the microdialysis fiber implanted in the hippocampus, caused a long lasting
      increase of extracellular hippocampal ACh level (360%) which was reversed when
      the drug was withdrawn from the perfusion solution. The stimulant effect of QUIS
      was antagonized by concomitant perfusion of GYKI (10 microM). No effect was seen
      on the basal ACh release when GYKI (10-100 microM) was perfused through the
      hippocampus. Local perfusion with tetrodotoxin (1 microM) decrease the basal
      release of ACh and prevented the QUIS-induced increase of ACh both in the
      hippocampus and striatum. Our in vivo neurochemical results indicate that
      hippocampal and striatal cholinergic systems are regulated by non-NMDA (probably
      AMPA) glutamatergic receptors located in the hippocampus and striatum.

PMID- 11821150
TI  - Alterations of purine and pyrimidine nucleotide contents in rat corticoencephalic
      cell cultures following metabolic damage and treatment with openers and blockers
      of ATP-sensitive potassium channels.
AB  - Rat corticoencephalic cell cultures were investigated by high performance liquid
      chromatography for changes in the levels of adenosine 5'-triphosphate (ATP),
      guanosine 5'-triphosphate (GTP), uridine 5'-triphosphate (UTP), cytidine 5'
      triphosphate (CTP), and the respective nucleoside diphosphates. Hypoxia was
      induced by gassing the incubation medium for 30 min with 100% argon. Removal of
      glucose was caused by washing the cultures in glucose-free medium at the
      beginning of the 30 min incubation period. Whereas hypoxia or glucose-deficiency
      alone failed to alter the nucleotide levels, the combination of these two
      manipulations was clearly inhibitory. Diazoxide (300 microM) an opener of ATP
      dependent potassium channels (K(ATP)) did not alter the nucleotide contents
      either in a normoxic and glucose-containing medium, or a hypoxic and glucose-free
      medium. By contrast, the K(ATP) channel antagonist tolbutamide (300 microM)
      aggravated the hypoxic decrease of nucleotide levels in a glucose-free medium,
      although it was ineffective in a normoxic and glucose-containing medium. Hypoxia
      and glucose-deficiency decreased the ATP/ADP and UTP/UDP ratios, but failed to
      change the GTP/GDP ratio. Diazoxide and tolbutamide (300 microM each) had no
      effect on the nucleoside triphosphate/diphosphate ratios either during normoxic
      or during hypoxic conditions. In conclusion, corticoencephalic cultures are
      rather resistant to in vitro ischemia. Although they clearly respond to the
      blockade of plasmalemmal K(ATP) channels (plasmaK(ATP)) by tolbutamide, these
      channels appear to be maximally open as a consequence of the fall in
      intracellular nucleotides and, therefore, diazoxide has no further effect.

PMID- 11821151
TI  - The novel anticonvulsant BIA 2-093 inhibits transmitter release during opening of
      voltage-gated sodium channels: a comparison with carbamazepine and oxcarbazepine.
AB  - (S)-(-)-10-acetoxy-10,11-dihydro-5H-dibenz/b,f/azepine-5-carboxamide (BIA 2-093)
      is endowed with high anticonvulsant activity and shares with carbamazepine (CBZ)
      and oxcarbazepine (OXC) the capability to inhibit voltage-gated sodium channels
      (VGSC). The present study was aimed to compare the effects of BIA 2-093, CBZ and
      OXC on the release of glutamate, aspartate, gamma-aminobutyric acid (GABA) and
      dopamine from striatal slices induced by the VGSC opener veratrine. The release
      of glutamate, aspartate, GABA and aspartate by veratrine from rat striatal slices
      was a concentration and time dependent process. All the three dibenzazepine
      carboxamide derivatives, BIA 2-093, CBZ and OXC inhibited in a concentration
      dependent manner (from 30 to 300 microM) the veratrine-induced release of
      glutamate, aspartate, GABA and dopamine. CBZ, OXC and BIA 2-093 were endowed with
      similar potencies in inhibiting veratrine-induced transmitter release. It is
      concluded that BIA 2-093, CBZ and OXC inhibit veratrine-induced transmitter
      release, which is in agreement with their capability to block VGSC. This property
      may be of importance for the anticonvulsant effects of BIA 2-093.

PMID- 11821152
TI  - Substrate-dependence of reduction of MTT: a tetrazolium dye differs in cultured
      astroglia and neurons.
AB  - 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction is
      widely used to evaluate cell proliferation and viability. MTT reduction is
      interpreted to be indicative of cellular metabolic activity, and the site of
      reduction includes both mitochondrial and cytosolic redox reactions. Astrocytes
      are believed to rely mainly on glycolysis for ATP generation, whereas neurons are
      considered to depend more on oxidative metabolism. The present study, therefore,
      tested the substrate-preference of glucose and its metabolites for MTT reduction
      in cultures of rat type 1 astroglia and neurons.MTT specific activity of
      astroglia was much higher than that of neurons. Astroglial MTT reducing activity
      in glucose-free medium or 2mM glucose with iodoacetate (5mM) was completely
      blocked. In glucose-depleted medium, 2mM lactate, pyruvate, malate, or acetate
      elicited minimal increases in MTT reduction by astroglia. In contrast, MTT
      reducing activity in neurons was enhanced two-fold by pyruvate and the reducing
      activity of lactate was equivalent to that of glucose, while malate had a small
      and acetate had no effect on MTT reduction. These results indicate that these two
      cell types differ markedly in their substrate-preferences for MTT reduction. In
      astroglia, MTT reduction reflects mainly cytosolic redox activity and is
      dependent on glyceraldehyde-3-phosphate dehydrogenase. In neurons, pyruvate
      dehydrogenase supports MTT reduction more effectively than glucose or lactate,
      even though both of these substrates can produce NADH and pyruvate.

PMID- 11821153
TI  - Kinetic characterization and immunodetection of ecto-ATP diphosphohydrolase (EC
      3.6.1.5) in cultured hippocampal neurons.
AB  - Extracellular ATP and adenosine modulate synaptic transmission in hippocampal
      neurons. ATP released from neural cells is hydrolyzed to adenosine by a chain of
      ecto-nucleotidases. ATP diphosphohydrolase hydrolyses ATP and ADP nucleotides to
      AMP and 5'-nucleotidase hydrolyses AMP to adenosine. In this work, we
      investigated the ATPase and ADPase activities of ATP diphosphohydrolase in
      cultured hippocampal neurons. The apparent Michaelis-Menten constant (K(m)) was
      233.9 +/- 14.6 and 221.8 +/- 63.6 microM, with a calculated maximal velocity
      (V(max), approximately) of 49.2 +/- 10.7 and 10.9 +/- 5.2 nmol Pi/mg protein/min
      for ATP and ADP, respectively. The horizontal straight line obtained in the
      competition plot indicated that only one active site is able to hydrolyze both
      substrates. Furthermore, we detected the presence of this enzyme using anti-CD39
      antibody, which strongly stained the soma of pyramidal and bipolar neurons, but
      the neurites connecting the cell clusters were also immunopositive. This antibody
      recognized three bands with a molecular mass close to 95, 80 and 60kDa in
      immunoblotting analysis. The present results show, for the first time, the
      kinetic and immunocytochemical characterization of an ATP diphosphohydrolase in
      cultured hippocampal neurons. Probably, the widespread distribution of this
      enzyme on the surface of neurons in culture could reflect its functional
      importance in studies of synaptic plasticity hippocampal.

PMID- 11821154
TI  - Mechanism of action of methylmercury on in vivo striatal dopamine release.
      Possible involvement of dopamine transporter.
AB  - Methylmercury (MeHg) produces significant increases in the spontaneous output of
      dopamine (DA) from rat striatal tissue. The mechanism through MeHg produces such
      increase in the extracellular DA levels could be due to increased DA release or
      decreased DA uptake into DA terminals. One of the aims of this study was to
      investigate the role of DA transporter (DAT) in the MeHg-induced DA release.
      Coinfusion of 400 microM MeHg and nomifensine (50 microM) or amphetamine (50
      microM) produced increases in the release of DA similar to those produced by
      nomifensine and amphetamine alone. In the same way, MeHg-induced DA release was
      not attenuated under Ca(2+)-free conditions or after pretreatment with reserpine
      (10 mg/kg i.p.) or tetrodotoxin (TTX), suggesting that the DA release was
      independent of calcium and vesicular stores, as well as it was not affected by
      the blockade of voltage sensitive sodium channels. Thus, to investigate whether
      depolarization of dopaminergic terminal was able to affect MeHg-induced DA
      release, we infused 75 mM KCl through the dialysis membrane. Our results clearly
      showed a decrease induced by MeHg in the KCl-evoked DA release. Taken together,
      these results suggest that MeHg induces release of DA via transporter-dependent,
      calcium- and vesicular-independent mechanism and it decreases the KCl-evoked DA
      release.

PMID- 11821155
TI  - Lung macrophages and dendritic cells express HLA-G molecules in pulmonary
      diseases.
AB  - HLA-G is selectively expressed in extravillous trophoblast of human placenta,
      which does not express classical HLA-A and -B molecules. Several studies report
      the role of HLA-G as a molecule involved in immune tolerance. By interacting with
      NK and T cells inhibitory receptors, HLA-G may downregulate their cytotoxicity
      functions. To appreciate the biologic and clinical relevance of HLA-G expression
      in lung diseases, HLA class I and HLA-G expression were analyzed in a panel of 36
      ex vivo neoplastic tissues and 8 non-neoplastic lung tissues. Immunohistochemical
      analysis was performed using a pan-HLA class I antibody (W6/32) and three
      different specific anti-HLA-G antibodies (87G, MEMG/9 and 4H84). These findings
      demonstrated that HLA-G products were not expressed in pulmonary structural
      cells. However, HLA-G molecules were detected in activated macrophages and
      dendritic cells infiltrating lung carcinomas (33%) and nontumoral pulmonary
      diseases (25%). HLA-G expression was not correlated with classical HLA
      alterations. No statistical correlation was found between HLA-G expression and
      clinical or biologic parameters except high tumor size. The expression of HLA-G
      in myelo-monocytic cells infiltrating lung pathologic tissues could alter
      antigenic presentation and contribute to decrease immune response efficiency,
      subsequently favoring the progression of tumoral or inflammatory processes.

PMID- 11821156
TI  - Overlap of direct and indirect alloreactive T-cell repertoires when MHC
      polymorphism is limited to the peptide binding groove.
AB  - The immune response to allogeneic-MHC molecules can be divided into two pathways
      based on the nature of the antigen. In the direct pathway, T cells respond to
      intact allogeneic MHC molecules, while in the indirect pathway T cells respond to
      allo MHC-derived peptides presented by self-MHC. The T-cell repertoire used in
      the direct and indirect alloresponse have not been compared in the same
      alloantigen system. Here, HLA-DR transgenic mice are used to compare the
      repertoires of T cells that respond to the same alloantigen through either the
      direct or the indirect pathway. Separate direct and indirect DR1 anti-DR4 T-cell
      lines were generated and the T cell repertoire was analyzed by molecular methods.
      The same six Vbeta families were involved in both direct and indirect cultures
      indicating a complete overlap in the Vbeta gene usage. A partial overlap at the
      clonotype level was observed as two identical clonotypic TCRs were observed in
      both direct and indirect cultures. Interestingly, the T cells observed in both
      cultures were public as the same TCRs were identified in cultures developed from
      independent mice. These results raise the prospect that immune suppression of
      selected T cells during allo-transplantation can simultaneously modulate direct
      and indirect alloreactivities.

PMID- 11821157
TI  - Developmentally regulated expression of survivin in the human thymus.
AB  - Survivin is a member of the inhibitor-of-apoptosis (IAP) family. It has been
      reported to be expressed during development, but not in differentiated normal
      tissue. However, its expression has been reported to be high in the thymus. To
      assess the role of survivin in human thymocyte development, we investigated the
      expression of survivin using reverse-transcriptase-polymerase chain reaction,
      flow cytometry, and immunohistochemistry in freshly isolated human thymocytes.
      Survivin was expressed in all thymocyte subsets but its expression level was
      developmentally regulated. Its expression was low in the double negative (DN)
      thymocytes, upregulated in double positive (DP) thymocytes, and was highest in
      the T-cell receptor(high), late DP thymocytes; it was then downregulated in the
      single positive thymocytes and negative in the peripheral blood T cells.
      Moreover, there was a positive correlation between the expression of survivin and
      that of CD69 and Bcl-2 in DP thymocytes. These results suggest that survivin may
      play an important role in the T-cell development in the human thymus.

PMID- 11821158
TI  - Allele-specific in situ analysis of microchimerism by fluorescence resonance
      energy transfer (FRET) in nonhuman primate tissues.
AB  - Rhesus monkeys are relevant models for tolerance induction. Hematopoetic
      chimerism is believed to be one of these strategies. The purpose of this study
      was to detect donor class I A locus allele specific mRNA in Rhesus monkey kidney
      recipient. We report here for the first time the results of frequency resonance
      energy transfer (FRET) hybridization technology in frozen tissues. Frequency
      resonance energy transfer hybridization was performed by using two Mamu-A*05
      allele specific oligonucleotides: a donor probe labeled with FITC and acceptor
      probe conjugated to Texas Red. The PCR-SSP microchimerism analysis method
      produced 0.05% and 0.5% of donor DNA for Mamu-DRB1*1002 and Mamu-DRBw301/3
      alleles, respectively. The donor cells were detected in mesenteric and/or
      inguinal lymph nodes, spleen, and liver, where the signal was the strongest. The
      results of FRET hybridization demonstrated the identical staining pattern in the
      recipient frozen tissues to that determined by PCR-SSP. Following FRET
      hybridization, the sections underwent immunohistochemical analysis, which
      revealed that donor cells had CD8+ phenotype. We demonstrate here for the first
      time that FRET in situ hybridization technique can be utilized for microchimerism
      analysis in frozen tissues. We conclude that using two donor mRNA specific
      oligonucleotide probes, rather than one, produce higher specificity.

PMID- 11821159
TI  - Polymorphisms of interferon-gamma gene CA-repeat and interleukin-10 promoter
      region (-592A/C) in Japanese type I diabetes.
AB  - We investigated the association of the polymorphisms of interferon-gamma gene
      (IFNG) CA-repeat and IL-10-592A/C with clinical heterogeneity of type I diabetes
      as well as susceptibility to type I diabetes. Two hundred seven Japanese type I
      diabetic patients and 160 healthy control subjects were studied in this case
      control study. No significant differences of global IFNG allele frequencies were
      found between controls and type I diabetic patients, and between each subgroup of
      the patients and controls. When compared with controls, the a12 allele was
      increased in the patients with age at onset <25 years (p 0.0241, p(c) = 0.1205),
      and a significant increased frequency of the a12 positive genotype was observed
      in the patients with age at onset <25 years (p(c) = 0.0121). There were no
      differences of IL-10-592 genotype and allele frequencies between controls and
      type I diabetes. However, the frequency of the -592*C allele was significantly
      increased in the patients with highly positive-GADab compared with controls (p(c)
      = 0.0060) or compared with the GADab-negative type I patients (p(c) = 0.0276).
      These results suggest that the IFNG CA-repeat and the IL-10-592A/C polymorphisms
      are not strong determinants of susceptibility to the development of type I
      diabetes in Japanese individuals. However, both the IFNG CA-repeat and the IL-10
      592A/C polymorphisms are associated with clinical heterogeneity in type I
      diabetes.

PMID- 11821160
TI  - Sequence-Based analysis of the HLA-DRB1 polymorphism in Metalsa Berber and
      Chaouya Arabic-speaking groups from Morocco.
AB  - To examine the genetic diversity in Morocco, the polymorphism at the HLA-DRB1
      locus was investigated in two populations: the Metalsa group consisting of
      Berbers from north Morocco (who speak the Tarifit language and live in the Nador
      area), and the Chaouya group who are Arabic-speaking people from west Morocco
      (Atlantic coast) living in the Settat area. The DRB1 alleles of 197 healthy
      unrelated individuals were identified by direct DNA sequencing of exon 2 using
      fluorescently-labeled primers. A total of 28 and 29 alleles at DRB1 locus were
      identified in the Metalsa and Chaouya groups, respectively. The most frequent
      alleles in the Metalsa group are DRB1*03011 (20.2%), DRB1*0701 (12.12%), and
      DRB1*1302 (11.11%). In the Chaouya group, DRB1*0701 (16.33%), DRB1*15011
      (12.76%), and DRB1*03011 (11.73%) are most common. Each population exhibits some
      specific variants and some uncommon alleles. The frequency of the DRB1*03011
      allele differs significantly between the two populations (p = 0.0311). The DRB1
      frequency distributions in the two groups suggest the effects of balancing
      selection. The interpopulation analysis highlighted a strong relatedness, based
      on genetic distances, between the two Moroccan groups and the other north
      Africans (the Moroccans from El Jadida area, Moroccan Souss Berbers, Algerians,
      and Tunisians), and to a lesser extent with the Iberians, French, and Ethiopians.

PMID- 11821161
TI  - Frequency of HLA-DPB1 disparities detected by reference strand-mediated
      conformation analysis in HLA-A, -B, and -DRB1 matched siblings.
AB  - The role of HLA-DPB1 as transplantation antigen is controversial. The frequency
      and relevance of HLA-DPB1 mismatch in hematopoietic stem cell transplantation are
      unknown. To ascertain the rate of HLA-DBP1 mismatch in siblings that had been
      matched for HLA-A, -B, and -DRB1, reference strand mediated conformation analysis
      (RSCA) a high resolution HLA typing method was used. Locus-specific primers were
      used to amplify the HLA-DPB1 locus. The PCR product was then hybridized with two
      fluorescein-labeled references and the duplexes were analyzed after
      electrophoresis in a short polyacrylamide gel. Among the 113 pairs of individuals
      tested, six HLA-DPB1 mismatches were identified, which corresponds to a frequency
      of 5.31 % (95% confidence interval 3.20%-7.42 %).

PMID- 11821163
TI  - Patients with active infection with Paracoccidioides brasiliensis present a Th2
      immune response characterized by high Interleukin-4 and Interleukin-5 production.
AB  - Paracoccidiodomycosis (PCM) is caused by the dimorphic fungus Paracoccidioides
      brasiliensis. In humans, the disease presents a broad spectrum of clinical
      manifestations, ranging from localized mucocutaneous lesions to a widespread
      manifestation with involving the mononuclear phagocyte system. In attempt to
      better understand the regulation of immune response during the infection, this
      study analyzed the production of regulatory and inflammatory cytokines in 25
      infected patients and 19 health controls. Regulatory and inflammatory cytokines
      were analyzed in supernatants of peripheral blood mononuclear cells (PBMC)
      stimulated with mitogens or soluble P. brasiliensis antigens. A pattern of Th2
      immune response was observed in patients, mainly attributed to a higher
      production of IL-4 and IL-5 than to a lower production of IFN-gamma. Patients
      with disseminated infection presented undetectable levels of IFN-gamma after
      antigen stimulation and high levels of IL-1beta, which were probably associated
      with the inflammatory reaction observed in multifocal infection.

PMID- 11821162
TI  - Distribution of class I and class III MHC antigens in the Tarasco Amerindians.
AB  - Class I and class III major histocompatibility complex (MHC) antigen frequencies
      were analyzed in 130 haplotypes from 33 families belonging to a group of
      Amerindians culturally and linguistically isolated for more than 12 centuries in
      Mexico: the Tarascos. The most frequent antigens in this ethnic group of the HLA
      A locus are: A2 (gf 0.353), A24 (gf = 0.223), A31 (gf = 0.184), and A28 (gf =
      0.161); and the most frequent of the HLA-B locus are: B35 (gf = 0.230), B39 (gf =
      0.192), B15 (gf = 0.146), and B5 (gf = 0.123). On the other hand, class III
      antigens demonstrated relatively high frequencies of the SC31 (frequency =
      0.561), SC01 (frequency = 0.076), and SC42 (frequency = 0.069) complotypes. Also
      important was the relatively high frequency of the HLA-B27 antigen (gf 0.061) and
      the SC33 complotype (frequency = 0.046), which are either absent or found
      infrequently in other Amerindian groups. Analysis of MHC haplotypes revealed that
      four of them have relatively high frequencies, these were the following:
      [B39;SC31] (11.6%), [B35;SC31] (11.6%), [B15;SC31] (8.0%), and [B5;SC31] (5.8%).
      Other MHC haplotypes had frequencies lower than 5.0%. The decreased frequency of
      BF alleles other than BF*S and the presence of the SC33 and SC32 complotypes
      suggest long time preservation from genetic admixture. This information
      withstands the basis for population genetic analysis and disease association
      studies in Mexican mestizos.

PMID- 11821164
TI  - Evaluation of the VTEC-Screen "Seiken" test for detection of different types of
      Shiga toxin (verotoxin)-producing Escherichia coli (STEC) in human stool samples.
AB  - An immunoassay for in vitro detection of Shiga (Vero) toxins Stx1 and Stx2 (VTEC
      Screen "Seiken") was compared with the verocell toxicity test (VCA) and an stx
      gene specific PCR for detection of Shiga toxin-producing E. coli (STEC) from 234
      human stool samples selectively enriched on sorbitol-MacConkey (SMAC) agar.
      Culturable STEC were isolated from 59 (25.2%) of the 234 stool specimens and were
      found to be distributed over 20 different O-serogroups. Fifty-three (89.8%) of
      the 59 STEC-positive samples were identified with the VTEC-Screen compared to 55
      (93.2%) with the PCR and 58 (98.3%) with the VCA. A possible false positive
      reaction with the VTEC-Screen was obtained with one sample and five samples
      showed aspecific reactions with both the test- and the control latex. The VTEC
      Screen detected all samples which contained Stx1 producing strains (77.9% of STEC
      positive samples) but was negative with six samples (10.2%) which contained Stx2
      and/or Stx2 variant producers, although secondary enrichment of on brain-heart
      infusion agar detected three of these to improve the detection rate to 94.9%.
      Examination of reference strains encoding different genotypes of stx(1) and
      stx(2) indicated that certain variants of Stx2 reacted poorly (Stx2d-Ount, Stx2e
      and Stx2ev) or not at all with the VTEC-Screen. Overall, however, the test was
      found to be accurate, rapid and easy to perform, thus being suitable for the
      routine screening of clinical stool specimens for STEC.

PMID- 11821165
TI  - Evaluation of seven different enzyme-linked immunosorbent assays for
      serodiagnosis of Staphylococcus aureus bacteremia.
AB  - OBJECTIVE: Serologic assays for Staphylococcus aureus antibodies were evaluated
      regarding their ability to differentiate between uncomplicated and complicated S.
      aureus bacteremia, between S. aureus and non-S. aureus bacteremia, and between S.
      aureus and non-S. aureus endocarditis. METHODS: Enzyme-linked immunosorbent
      assays (ELISAs) were performed to measure Ig G antibodies against seven S. aureus
      antigens (peptidoglycan, teichoic acid, S. aureus ultrasonicate, whole S. aureus
      cells, alpha-toxin, lipase and capsular polysaccharide) in 129 patients with S.
      aureus bacteremia (including 51 with endocarditis), 78 patients with non-S.
      aureus bacteremia (including 27 with endocarditis) and 100 febrile non-bacteremic
      controls. RESULTS: Whole-cell ELISA was the most sensitive assay. The specificity
      of all assays was low. Two different combinations of ELISAs for whole cells,
      teichoic acid,alpha-toxin, lipase and capsular polysaccharide did distinguish
      between S. aureus and non-S. aureus endocarditis, but not between uncomplicated
      and complicated S. aureus bacteremia.

PMID- 11821166
TI  - Susceptibility of human isolates of Salmonella typhimurium DT 104 to
      antimicrobial agents used in human and veterinary medicine.
AB  - Multiple antibiotic resistance is frequently observed among strains of Salmonella
      typhimurium DT104. We examined the antibiotic resistance patterns of 240 human
      isolates submitted from central and northern Alberta to our laboratory for
      confirmatory testing during 1996-1999. Broth microdilution MIC panels included
      antibiotics proposed by the Canadian National Enteric Disease Surveillance
      Committee for human and animal isolates. Seven different susceptibility patterns
      were observed. The two most common patterns accounted for 83% of isolates; 48%
      were susceptible to all antibiotics tested and 35% were resistant to ampicillin,
      tetracycline, chloramphenicol and amoxicillin-clavulanate. All strains were
      susceptible to enrofloxacin and trovafloxacin with variable resistance to
      kanamycin and chloramphenicol. There were more susceptible isolates observed in
      1996 and 1997 than in 1998 and 1999, but multiple resistant isolates were found
      throughout the study period.

PMID- 11821167
TI  - A comparative study of the etiology of adult upper and lower respiratory tract
      infections in the community.
AB  - Lower respiratory tract infection and upper respiratory tract infection (URTI)
      are very common, but the etiology is not diagnosed in routine practice. The
      objective of this study was to determine and compare the frequency distribution
      of the various infectious etiologies for these diseases. One hundred seventy five
      adults in the community with febrile LRTI and 75 with febrile URTI were included
      in a purely serologically based prospective study. Paired sera were obtained for
      each of the patients and were tested by EIA or immunofluorescence methods to
      identify 14 different pathogens. Only a significant change in antibody titers
      between the paired sera was considered diagnostic. At least one infectious
      etiology was identified in 167 patients (67%). In the LRTI group, infection with
      at least one of 7 respiratory viruses was found in 88 patients (50%). One of the
      atypical pathogens was found in 40 patients (23%), of these Legionella spp. in 19
      (11%) and Mycoplasma pneumoniae in 18 (10%). A bacterial etiology was found in 19
      patients (11%), of these Streptococcus pneumoniae in 8 (5%) and beta-hemolytic
      streptococci group A in 5 (3%). The frequency distribution of etiologies in the
      URTI group was not significantly different from the LRTI group, except for M.
      pneumoniae that was identified in only one patient with URTI (p = 0.015). More
      than one etiologic agent was found in 42 (17%) of the patients. LRTI is caused by
      a broad spectrum of etiologies, with respiratory viruses predominating and a
      moderate, but significant, prevalence of atypical pathogens. The frequency
      distribution of etiologies for URTI is similar to LRTI. In a significant
      proportion of patients with URTI and LRTI there is serologic evidence of
      infection with more than one pathogen. The justification and benefit of
      distinguishing between URTI and LRTI in routine clinical work is doubtful. When a
      decision is reached to treat RTI patients with an antibiotic, it is logical to
      use a macrolide or tetracycline.

PMID- 11821168
TI  - Compliance with NCCLS approved standard M22-A2 for bacteriologic media quality
      assurance: a survey of 124 Ontario microbiology laboratories.
AB  - OBJECTIVE: The purpose of this QMP-LS patterns-of-practice survey was to
      determine quality assurance (QA) processes used in Ontario for purchased and in
      house culture media, and compliance with recommended practices. METHODS: QMP-LS
      required laboratories to submit copies of media QC records for August to October
      1998. Target media were blood agar, chocolate agar, MacConkey agar, sorbitol
      MacConkey agar (SMAC), Campylobacter agar, and selective media for pathogenic
      Neisseria spp. Procedures for acquisition and maintenance of QC stock cultures,
      media-type specific QC strains, time and temperature of incubation, and the test
      inoculum were required. Data were captured and analysed using Microsoft Excel.
      RESULTS: Marked variability and inadequacy of media QC records of 124
      participating laboratories was noted. 12/124 prepared media in-house, most did
      not comply with NCCLS QA recommendations. Those purchasing prepared media
      frequently did not comply with NCCLS recommendations. In-house QC was not
      performed by 9% for chocolate agar, 87% for MacConkey agar without crystal
      violet, and 53% for SMAC agar. Recommended ATCC strains were used by less than
      half of participants. Time and temperature of incubation of the QC plates were
      not always appropriate. Only 65/117 laboratories used a correct inoculum to test
      the sensitivity and selectivity of media for pathogenic Neisseriae. Physical
      characteristics of prepared media were rarely recorded. Most laboratories were
      not aware of their supplier's QC protocols. DISCUSSION: Few Ontario laboratories
      comply with the NCCLS recommendations for QA of culture media. Major compliance
      failures were not performing QC at all, inappropriate choice of QC bacterial
      strains, and inoculum used. Incomplete record keeping was common and methods for
      maintaining stock cultures were sub-optimal. External quality assessment of this
      important parameter of microbiology practice needs to be undertaken on an ongoing
      basis.

PMID- 11821169
TI  - A comparative evaluation of dot immunobinding assay (Dot-Iba) and polymerase
      chain reaction (PCR) for the laboratory diagnosis of tuberculous meningitis.
AB  - The results of a Dot immunobinding assay (Dot Iba) for the detection of
      mycobacterial antigen in the cerebrospinal fluid (CSF) of 45 patients with
      tuberculous meningitis (TBM) were compared with the results of a polymerase chain
      reaction (PCR) for the detection of Mycobacterium tuberculosis. In eight patients
      with culture proven TBM, Dot-Iba gave positive results, while PCR yielded
      positive results only in six patients. The overall sensitivities of Dot-Iba and
      PCR in 37 patients with culture negative (probable) TBM were 75.67% and 40.5%
      respectively. Dot-Iba, in contrast to PCR is a rapid and relatively easier
      method. More importantly, Dot-Iba is suitable for the routine application for the
      laboratory diagnosis of TBM and therefore best suited to laboratories in the
      developing world.

PMID- 11821170
TI  - Urine D-arabinitol/L-arabinitol ratio in diagnosing Candida infection in patients
      with haematological malignancy and HIV infection.
AB  - Adult patients with hematologic malignancies along with HIV infected patients
      were prospectively studied to determine the performance of urine D-arabinitol/L
      arabinitol (DA/LA) ratio in diagnosing invasive candidiasis. Ten evaluable
      febrile neutropenic patients had proven invasive candidiasis and elevated DA/LA
      ratios were found in 5. Invasive candidiasis with normal DA/LA ratios was most
      frequently due to Candida krusei infection. This Candida species is a non
      producer of arabinitol. Only 4 of 81 febrile neutropenic patients given either
      antifungal prophylaxis or empiric antifungal treatment had elevated DA/LA ratios.
      Only 1 of 15 HIV positive patients with either oropharyngeal or esophageal
      candidiasis had elevated DA/LA ratios. Widespread use of fluconazole prophylaxis
      in bone marrow transplantation patients at the study hospital has led to an
      increased prevalence of C. krusei infection. This is the likely reason for the
      low sensitivity of the test in proven and suspected invasive Candida infections
      reported here.

PMID- 11821171
TI  - Evaluation of sequential testing strategies using non-amplified and amplified
      methods for detection of Chlamydia trachomatis in endocervical and urine
      specimens from women.
AB  - Nucleic acid amplification tests (NAAT) are more sensitive than other methods for
      the diagnosis of Chlamydia trachomatis (CT) genital infections. Two unique
      sequential testing strategies that employed two different commercial NAAT methods
      to detect CT in a population of women with widely varying infection risk were
      evaluated. Specimens from 504 women aged 15 to 75 years were studied. Two
      endocervical swabs and a urine sample were collected from each woman. One swab
      was initially tested using the Access enzyme immunoassay (EIA) (Beckman). An
      aliquot from the EIA extraction was subsequently amplified using the COBAS
      AMPLICOR CT assay (PCR) (Roche). The second swab was initially tested using the
      PACE 2 CT hybridization assay (Gen-Probe). An aliquot was pipetted off prior to
      performing the PACE 2 assay and also amplified using the AMP-CT assay (TMA) (Gen
      Probe). Urine samples were tested for CT using both NAAT methods. True CT
      infections were defined as any woman that was confirmed to be positive on both
      NAAT results from endocervical swabs. The results of all other CT assays were
      compared against this expanded gold standard. 28 women were confirmed to have CT
      infection giving an overall prevalence of 5.6%; low-risk women had a rate of 1.3%
      while high-risk women had a rate of 9.8%. NAAT methods have a higher sensitivity
      for detecting CT cervicitis when swabs are tested compared to urine. The positive
      predictive value of NAAT is decreased when testing low risk women. Limited
      automation makes it difficult to test a high volume of samples (i.e., > 100 swabs
      and/or urines) using either of these NAAT methods and continue to provide same
      day results. Laboratories performing CT testing must define the female population
      served so that appropriate diagnostic strategies can be employed.

PMID- 11821172
TI  - Activity of cefditoren against beta-lactamase-positive and -negative Haemophilus
      influenzae and Moraxella catarrhalis.
AB  - Cefditoren is a novel broad-spectrum oral cephalosporin. To determine the
      influence of beta-lactamase production on cefditoren activity, 1,170 H.
      influenzae and 641 M. catarrhalis isolated during 2000 were tested by NCCLS broth
      microdilution methodology (M7-A5, 2000). Against H. influenzae the potency of
      cefditoren (MIC(90,) 0.015 microg/mL) was similar to that of ceftriaxone
      (MIC(90,) < or = 0.015 microg/mL) and levofloxacin (MIC(90,) 0.015 microg/mL),
      and its MIC distribution was unaffected by beta-lactamase production. In
      comparison, the beta-lactamase status of M. catarrhalis affected the potency of
      all beta-lactams tested, including cefditoren, as well as trimethoprim
      sulfamethoxazole. However, regardless of the presence of beta-lactamase,
      cefditoren demonstrated potent activity, as concentrations of 0.5 and 1 microg/mL
      inhibited 93.1 and 100% of M. catarrhalis isolates, respectively. We conclude
      that cefditoren is highly active in vitro against beta-lactamase-positive H.
      influenzae and M. catarrhalis.

PMID- 11821173
TI  - In vitro susceptibility of recent clinical isolates of pneumococci to the
      investigational cephalosporin cefditoren.
AB  - From February to June 2000, 2,597 isolates of Streptococcus pneumoniae were
      prospectively collected from 146 clinical laboratories across the United States
      (US) and tested to evaluate the in vitro activity of cefditoren, an
      investigational oral cephalosporin. In all, 2,492 isolates (96.0%) had a
      cefditoren MIC of 0.5 microg/mL or less, 74 isolates (2.8%) had an MIC of 1
      microg/mL, 30 isolates (1.2%) had an MIC of 2 microg/mL, and 1 isolate (<0.1%)
      had an MIC of 4 microg/mL. Among the beta-lactams tested, the rank order of
      potency (MIC(90,) microg/mL) was cefditoren (0.5) > ceftriaxone (1) > amoxicillin
      clavulanate (2) > cefuroxime (4) > cefprozil (8). Penicillin-resistant isolates
      (n = 443; 17.1%) were inhibited by lower concentrations (MIC(90,) microg/mL; MIC
      range,) of cefditoren (1; 0.03-4) than ceftriaxone (2; 0.25- > 2), amoxicillin
      clavulanate (8; 0.5- > 8), cefuroxime (16; 2- > 16), and cefprozil (32; 2- > 32).
      Cefditoren MIC(90)s against cefuroxime-resistant (n = 640) and ceftriaxone
      resistant (n = 89) isolates were 1 and 2 microg/mL, respectively. All isolates
      with reduced susceptibility to cefditoren (MIC, 2 or 4 microg/mL; n = 31) were
      resistant to penicillin, cefuroxime, and ceftriaxone. The potent in vitro
      activity of cefditoren against a recent US collection of pneumococci as
      demonstrated in this study supports its continued development for oral empiric
      therapy in outpatients with respiratory tract infections.

PMID- 11821174
TI  - Influence of CO(2) incubation on quinolone activity against Streptococcus
      pneumoniae and Haemophilus influenzae.
AB  - Quinolone activity can be influenced by the pH change that occurs during CO(2)
      incubation when testing capnophilic organisms such as Streptococcus pneumoniae
      and Haemophilus influenzae. This study compares the activity of ciprofloxacin,
      clinafloxacin, enrofloxacin, fleroxacin, grepafloxacin, levofloxacin,
      moxifloxacin, norfloxacin, ofloxacin, pefloxacin, sparfloxacin, trovafloxacin,
      and the glycopeptide vancomycin, under ambient air and supplemental CO(2)
      incubation conditions. Etest (AB BIODISK, Solna, Sweden) was used to determine
      the MIC values of 30 S. pneumoniae strains including S. pneumoniae ATCC 49619 and
      6030; and 29 H. influenzae strains including H. influenzae ATCC 49247 and 49766,
      incubated with and without 5% CO(2.) Reference broth microdilution and agar
      dilution tests were performed under similar conditions. Results determined that
      MIC values of all quinolones agreed (> or = 95%) within +/- one log(2) dilution
      for the three test methods tested under identical incubation conditions.
      Quinolone MICs for S. pneumoniae were minimally influenced by CO(2,) while MIC
      values for H. influenzae ranged from 0.5 to two log(2) dilutions higher when
      incubated in the CO(2) environment. The differences in quinolone activity against
      H. influenzae may be due to a combination of pH effects and enhanced growth in
      the CO(2) test conditions. Quality control and interpretative criteria,
      especially for H. influenzae and quinolones published by the National Committee
      for Clinical Laboratory Standards, may not be fully applicable to results
      obtained under CO(2) incubation. This may generate potential therapeutic
      interpretive dilemmas in the susceptibility testing of H. influenzae, where
      clinical isolates require CO(2) to sustain acceptable growth.

PMID- 11821175
TI  - Clinical evaluation of the Vitek automated system with cards GNS 122 and 127 and
      VTK-R07.01 software for antimicrobial susceptibility testing of Pseudomonas
      aeruginosa.
AB  - The performance of the Vitek Automated Susceptibility Testing System software
      version VTKR07.01 (bioMerieux Vitek, Hazelwood, MO), for testing Pseudomonas
      aeruginosa was evaluated by comparing results for 200 clinical isolates with
      those of disk diffusion and manual broth microtiter dilution testing. For
      cefepime, the restricted major error rate was 0.53% and the minor error rate was
      12.5%. For piperacillin, the restricted major error rate was 2.15%. For
      ticarcillin/clavulanic acid, restricted very major and major error rates of 6.5%
      and 3.2%, respectively, occurred. The results of our study indicate that the
      Vitek system performs within acceptable limits when testing piperacillin, but
      remains problematic for testing cefepime and ticarcillin-clavulanic acid.

PMID- 11821176
TI  - In vitro synergy testing of levofloxacin, ofloxacin, and ciprofloxacin in
      combination with aztreonam, ceftazidime, or piperacillin against Pseudomonas
      aeruginosa.
AB  - The synergistic potential of levofloxacin, ofloxacin and ciprofloxacin combined
      with aztreonam, ceftazidime, or piperacillin was compared using 24 strains of
      Pseudomonas aeruginosa with varying susceptibility profiles. Levofloxacin and
      ciprofloxacin demonstrated similar in vitro activity, with ofloxacin
      demonstrating less activity compared to the other agents. Predominantly additive
      effects were seen with all combinations, with no significant differences detected
      between the fluoroquinolone agents.

PMID- 11821177
TI  - Cardiobacterium hominis bioprosthetic mitral valve endocarditis presenting as
      septic arthritis.
AB  - We report an unusual case of Cardiobacterium hominis bioprosthetic valve
      endocarditis presenting as septic arthritis. This remarkable presentation had
      clinical features consistent with endocarditis generally associated with highly
      virulent pathogens. A literature search has failed to disclose a report of septic
      arthiritis as a manifestation of C. hominis endocarditis.

PMID- 11821179
TI  - Quantify.

PMID- 11821180
TI  - Trypan blue with a viscoelastic agent.

PMID- 11821182
TI  - Secondary LASIK.

PMID- 11821184
TI  - Correcting astigmatism.

PMID- 11821186
TI  - Treating a hyperopic shift after refractive surgery.

PMID- 11821187
TI  - Effect of optic size on PCO.

PMID- 11821188
TI  - Consultation section. Cataract surgical problem.

PMID- 11821198
TI  - Managing anterior capsule contraction by mechanical widening with vitrector-cut
      capsulotomy.
AB  - We present a technique, vitrectorhexis, in which a vitrector-cut capsulotomy is
      used to treat anterior capsule contraction syndrome. A vitrector handpiece is
      used to remove all fibrous capsule tissue and residual lens epithelial cells from
      the anterior chamber. Vitrectorhexis may be an alternative to neodymium:YAG laser
      capsulotomy as it decreases the risk of radial tear extension to the zonules and
      of secondary IOL decentration. The technique was used in a 77-year-old man with
      capsulorhexis contraction syndrome and extensive fibrosis after
      phacoemulsification with silicone piggyback intraocular lens implantation. One
      day postoperatively, visual acuity improved from 20/60 to 20/30 and the anterior
      chamber reaction was minimal. At 1 month, best corrected visual acuity was 20/20.
      The IOL was well centered at 6 months.

PMID- 11821199
TI  - Transparent irrigation cannula for bimanual lens cortex removal.
AB  - A transparent irrigation cannula was developed to facilitate bimanual removal of
      subincisional lens cortex after phacoemulsification. The cannula allows
      visualization of the proximal cortex and provides ample inflow to maintain an
      inflated anterior chamber even at a high aspiration pressure.

PMID- 11821200
TI  - Biometry of cataractous eyes using partial coherence interferometry: clinical
      feasibility study of a commercial prototype I.
AB  - PURPOSE: To evaluate the clinical feasibility of the prototype version of a
      commercial partial coherence interferometry instrument (axial length measurement,
      ALM, Carl Zeiss Jena) for noninvasive, high-precision biometry in cataractous
      eyes. SETTING: Department of Ophthalmology, Vienna General Hospital, and
      Institute of Medical Physics, University of Vienna, Austria. METHODS: The
      preoperative axial length in 49 eyes of 37 cataract patients was measured with
      the commercial (ALM) and laboratory (PCI) prototypes of the partial coherence
      interferometry instrument, as well as with immersion ultrasound (IUS). RESULTS:
      Axial length measurements with the ALM and PCI did not differ significantly (P =
      .23). Both prototypes assessed longer axial lengths than the IUS technique (P <
      .0001; median 203 microm; range -476 to +635 microm). The precision of the axial
      length measurement was 18 microm, 28 microm, and 54 microm with the PCI, ALM, and
      IUS, respectively. CONCLUSIONS: Partial coherence tomography is a high-precision,
      high-resolution, noncontact biometric technique.The commercial PCI prototype is
      practical in clinical use, with improved comfort for patients, no need for
      anesthesia, and a reduced risk of infection. However, the difference between the
      PCI and IUS in axial length measurement must be considered when using the
      constants supplied by intraocular lens (IOL) manufacturers for IOL power
      calculations.

PMID- 11821201
TI  - Refractive outcome of cataract surgery using partial coherence interferometry and
      ultrasound biometry: clinical feasibility study of a commercial prototype II.
AB  - PURPOSE: To evaluate the refractive outcome of cataract patients 3 months
      postoperatively using optical biometry obtained with a prototype version (axial
      length measurement, ALM, Carl Zeiss Jena) of the commercial partial coherence
      interferometry (PCI) instrument (IOLMaster, Carl Zeiss Jena). SETTING: Department
      of Ophthalmology, Vienna General Hospital, and Institute of Medical Physics,
      University of Vienna, Austria. METHODS: Forty-five patients with age-related
      cataract in both eyes were scheduled for bilateral cataract surgery. Axial length
      was measured preoperatively with a prototype (ALM) of the commercial PCI
      instrument as well as with immersion ultrasound (IUS). Immersion US was performed
      by a single experienced investigator. In each patient, the first eye was randomly
      assigned to receive an intraocular lens (IOL) using the Holladay IOL power
      formula based on ALM or IUS biometry. The other biometric technique was used in
      the contralateral eye. Subjective refractive outcome was assessed 3 months
      postoperatively. RESULTS: Refractive outcomes with the 2 techniques did not
      differ significantly (P = .28). The mean numerical error (MNE) (the difference
      between the refractive outcome 3 months postoperatively and the predicted
      spherical equivalent) was 0.13 diopter (D) and 0.03 D for the ALM and IUS,
      respectively. The mean absolute error (MAE) (the absolute value of MNE) was 0.48
      D (range 0.00 to 1.58 D) and 0.46 D (range 0.01 to 1.92 D) with the ALM and IUS,
      respectively. By recalculating the surgeon factor retrospectively to correct the
      Holladay formula to obtain a postoperative MNE of zero, a theoretical MAE of 0.46
      D was obtained with both biometry techniques. CONCLUSIONS: Refractive outcome in
      cataract patients using PCI biometry was as good as that achieved with optimized
      IUS. However, the difference in axial length measured by the ALM compared to that
      measured by IUS must be considered when using the IOL A-constants supplied by the
      manufacturers.

PMID- 11821202
TI  - Accuracy and reproducibility of biometry using partial coherence interferometry.
AB  - PURPOSE: To determine whether partial coherence interferometry is comparable to
      standard contact ultrasonic biometry in accuracy, reproducibility, and ease of
      use. SETTING: Academic university practice. METHODS: In this prospective study,
      simultaneous biometry was performed in 91 consecutive patients (111 eyes) using
      partial coherence interferometry (IOLMaster, Zeiss Humphrey Systems) and
      ultrasonic biometry (I(3), Innovative Imaging, Inc.). The differences between the
      predicted spherical equivalent in diopters (D) and the actual results with both
      techniques were compared. RESULTS: The IOLMaster was significantly better in the
      mean absolute error (0.533 D +/- 0.589 [SD] versus 0.757 +/- 0.723 D; P = .012)
      and the percentage of eyes within +/-0.5 D (61.2% versus 42.3%; P = .003) and +/
      1.0 D (87.4% versus 77.5%; P =.05) of the predicted refraction. CONCLUSION: The
      IOLMaster was more accurate and reproducible than the contact ultrasonographic
      technique.

PMID- 11821203
TI  - Immersion A-scan compared with partial coherence interferometry: outcomes
      analysis.
AB  - PURPOSE: To compare 2 methods of axial length measurement, immersion
      ultrasonography and partial coherence interferometry, and to elucidate surgical
      outcomes based on immersion measurements. SETTING: Oregon Eye Institute, Eugene,
      Oregon, USA. METHODS: Axial length measurements in 50 cataractous eyes were
      obtained by optical biometry (IOLMaster, Zeiss Humphrey Systems) and immersion
      ultrasound (Axis II, Quantel Medical), and the results were compared. Intraocular
      lens (IOL) power calculations in the same eyes after cataract extraction and
      posterior chamber IOL implantation were evaluated retrospectively based on the
      postoperative spherical equivalent prediction error. RESULTS: Immersion
      ultrasonography and partial coherence interferometry measurements correlated in a
      highly positive manner (correlation coefficient = 0.996). Outcomes analysis
      demonstrated 92.0% of eyes were within +/-0.5 diopter of emmetropia based on
      immersion axial length measurements. CONCLUSION: Immersion ultrasonography
      provided highly accurate axial length measurements and permitted highly accurate
      IOL power calculations.

PMID- 11821204
TI  - Anterior chamber depth measurement: a-scan versus optical methods.
AB  - PURPOSE: To evaluate methods of measuring anterior chamber depth (ACD) before and
      after cataract surgery. SETTING: St. Erik's Eye Hospital, Stockholm, Sweden.
      METHODS: A-scan (BVI Axis) and Scheimpflug imaging (Nidek EAS-1000) were used to
      measure ACD preoperatively and 6 and 18 weeks after phacoemulsification with
      implantation of a poly(methyl methacrylate) (PMMA) intraocular lens (IOL) in 23
      patients. Because of a large systematic difference between the 2 methods,
      measurement with Orbscan (Orbtek) and optical pachymetry (Haag-Streit) were
      included when measurements were repeated 36 weeks postoperatively. A t test for
      paired observations was used for statistical analysis. RESULTS: Preoperatively,
      the mean A-scan measurements were significantly shorter than the Scheimpflug
      values: 3.05 mm +/- 0.36 (SD) and 3.37 +/- 0.35 mm, respectively (P < .001). At 6
      weeks, the difference was more pronounced: 3.73 +/- 0.26 mm and 4.65 +/- 0.33 mm,
      respectively (P < .001). At 36 weeks, the A-scan and Scheimpflug values remained
      unchanged. The results of the Scheimpflug measurements were confirmed with
      optical pachymetry and Orbscan analysis. CONCLUSIONS: There was good agreement
      between results obtained with 3 methods based on optical principles. Considering
      the basic and simple measurement principle of these instruments, they appear to
      provide the correct result. The A-scan equipment used in this study is unsuitable
      for determination of ACD in eyes with PMMA IOLs.

PMID- 11821205
TI  - Comparison of corneal pachymetry using ultrasound and Orbscan II.
AB  - PURPOSE: To compare Orbscan II pachymetry with ultrasonic pachymetry in eyes
      having corneal refractive surgery. SETTING: Instituto Oftalmologico de Alicante,
      Alicante, Spain. METHODS: In this comparative prospective study, 72 eyes (36
      patients) were divided into 4 groups: Group 1, 16 eyes with haze after
      photorefractive keratectomy (PRK); Group 2, 12 eyes with no haze after PRK; Group
      3, 24 eyes that had uneventful laser in situ keratomileusis; Group 4, 20 normal
      eyes. The corneal thickness was measured in all eyes by the Orbscan II (version
      3.27.10, Orbtek Inc.) and then by ultrasonic pachymetry (DHC 500, Technology
      Inc.). RESULTS: The results between the 2 systems of pachymetry were significant
      in Group 1 (P < .0001) and not significant in Groups 2, 3, and 4 (P = .056, P =
      .051, and P = .68, respectively). A statistically significant correlation existed
      between the grade of haze and the decrease in Orbscan readings (C = -0.821, P <
      .0001). CONCLUSION: The Orbscan II pachymetry measurements correlated with the
      ultrasound measurements in eyes with clear corneas. Haze after PRK decreased the
      Orbscan pachymetry.

PMID- 11821206
TI  - Accuracy of Orbscan optical pachymetry in corneas with haze.
AB  - PURPOSE: To compare corneal thickness measurements with the Orbscan instrument
      (Orbtek, Inc.) and an ultrasonic pachymeter (Alcon Surgical) in corneas with
      haze. SETTING: Department of Ophthalmology and Otolaryngology, University of
      Bari, Bari, Italy. METHODS: Six eyes of 6 patients having phototherapeutic
      keratectomy for treatment of grade 2+ haze were assessed preoperatively and
      postoperatively by Orbscan optical pachymetry and ultrasonic pachymetry.
      Contralateral transparent untreated corneas of the same patients were used as
      controls. Two Orbscan and 5 ultrasound pachymetry measurements were performed at
      each visit and the mean values recorded. The accuracy and repeatability of the
      measurements were evaluated. RESULTS: Preoperatively, the median corneal
      thickness in the 6 eyes with haze was 512.7 microm by ultrasonic pachymetry and
      375.0 microm by optical pachymetry. The mean difference of 143.1 microm was
      statistically significant (Wilcoxon signed rank test, P= .0277). Postoperatively,
      the median pachymetry was 439.0 microm and 433.0 microm, respectively; the mean
      difference was 10.7 microm (P= .0277). In the control group, the median
      ultrasonic pachymetry was 530.9 microm and the median optical pachymetry, 529.0
      microm; the mean difference was 4.7 microm (P= .1730). Precision was good in all
      groups; the standard deviation was less than 6.0 microm. CONCLUSIONS: The Orbscan
      system showed a decreased accuracy in measuring corneal thickness when clinically
      significant haze was present. The repeatability of the measures was good,
      suggesting that the cause of error lies in the optical acquisition process.

PMID- 11821207
TI  - Accuracy and predictability of the compensatory function of Orbscan II in
      intraocular pressure measurements after laser in situ keratomileusis.
AB  - PURPOSE: To evaluate the usefulness of the compensatory function of Orbscan II
      (Orbtek, Bausch & Lomb) for measuring postoperative intraoperative pressure (IOP)
      in laser in situ keratomileusis (LASIK) patients. SETTING: Department of
      Ophthalmology, Ilsan Paik Hospital, Inje University, Ilsan, Korea. METHODS: Two
      hundred ten patients had LASIK using the Hansatome microkeratome (Bausch & Lomb)
      and the MEL 70 G-scan laser (Aesclepion-Meditec) and were examined
      retrospectively. The patients included in the study were divided into 2 groups:
      Group 1, 123 eyes with less than -6.0 diopters (D) of myopia; Group 2, 60 eyes
      with more than -6.0 D of myopia. The IOP was measured preoperatively and 2 and 4
      weeks after LASIK using a noncontact tonometer (NCT CT-60, Topcon). The results
      were corrected with the Orbscan II program. RESULTS: The mean IOPs in Group 1
      were 16.35 mm Hg +/- 2.90 (SD) preoperatively, 10.80 +/- 2.21 mm Hg at 2 weeks,
      and 10.63 +/- 2.28 mm Hg at 4 weeks. After compensation with Orbscan II, the 2
      week and 4-week values were 16.81 +/- 3.14 mm Hg and 16.68 +/- 3.22 mm Hg,
      respectively. The mean IOPs in Group 2 were 17.63 +/- 2.93 mm Hg, 10.07 +/-1.55
      mm Hg, and 10.43 +/- 1.84 mm Hg, respectively; after compensation, they were
      18.40 +/- 4.09 mm Hg and 18.05 +/- 4.09 mm Hg, respectively. After compensation
      with Orbscan II, there were no statistically significant differences between the
      preoperative and postoperative IOPs. CONCLUSIONS: Orbscan II may help predict
      actual IOP values after LASIK and avoid the misinterpretation of high IOPs as
      normal IOPs.

PMID- 11821208
TI  - Reproducibility of standardized retroillumination photography for quantification
      of posterior capsule opacification.
AB  - PURPOSE: To determine the short-term reproducibility of standardized digital
      retroillumination images of regeneratory posterior capsule opacification (PCO)
      using the photographic setup at 1 institution. SETTING: Department of
      Ophthalmology, University of Vienna, Vienna, Austria. METHODS: In this
      prospective study, 60 retroillumination images of 30 eyes with varying degrees of
      PCO and different types of intraocular lenses were acquired with a standardized
      digital coaxial retroillumination system. Two images were taken per eye with a 1
      minute interval between images. Ten other eyes were photographed in the same way
      but with a 5-day interval between the 2 images. All images were evaluated with a
      fully automated, objective PCO analysis software in which the PCO score was from
      0 to 100. The 2 results (A, B) in each eye were compared, and the differences
      were calculated. RESULTS: There was a high correlation between the A and B
      results (r = 0.99). The mean absolute difference was 3.7%. The repeatability
      coefficient was 8.8%. CONCLUSION: Digital coaxial retroillumination photography
      provided quick acquisition of regeneratory PCO images. It provided excellent
      image quality and high reproducibility. The technique forms a good basis for
      automated quantification of PCO with new software systems.

PMID- 11821209
TI  - Assessment of anterior capsule opacification: photographic technique and
      quantification.
AB  - PURPOSE: To develop and evaluate a standardized slitlamp photographic technique
      to document and quantify anterior capsule opacification (ACO) in the pseudophakic
      eye. SETTING: University of Vienna, Medical School, Department of Ophthalmology,
      Vienna, Austria. METHODS: In this prospective study, slitlamp photographs were
      taken in 29 eyes of 19 patients with ACO of varying degrees and intraocular
      lenses of different materials. Digital slitlamp photographs were taken by 2
      examiners using a standardized protocol. The intensity of anterior fibrosis was
      evaluated using subjective grading by 2 masked examiners and by image analysis.
      RESULTS: A standardized protocol was developed for documentation of ACO. The
      intraexaminer (or short-term) reproducibility (r = 0.96, P < .01) and
      interexaminer reproducibility (r = 0.93, P < .01) were excellent. The results of
      image analysis used to objectively quantify ACO correlated with the subjective
      grading (r = 0.95, P < .01). CONCLUSION: This standardized technique of slitlamp
      photography and image analysis provided reproducible documentation and can
      therefore serve as a basis for the quantification of ACO.

PMID- 11821210
TI  - Comparison of a ray-tracing refractometer, autorefractor, and computerized
      videokeratography in measuring pseudophakic eyes.
AB  - PURPOSE: To test the accuracy and reliability of the first-generation prototype
      of Tracey-1, a ray-tracing refractometer. SETTING: Cullen Eye Institute, Baylor
      College of Medicine, Houston, Texas, USA. METHODS: The refractive spherical
      equivalent (SE) and astigmatism measured by Tracey-1, subjective manifest
      refraction (MR), and autorefraction (AR) (Nidek AR-3300) were compared in 58
      pseudophakic eyes of 44 patients with a mean age of 69.95 years +/- 8.6 (SD). The
      astigmatic values obtained from Tracey-1 and computerized videokeratography were
      also compared. Astigmatism values were compared using power vector analysis.
      RESULTS: The mean SEs measured by MR, Tracey, and AR were -0.76 diopter (D) +/-
      0.96 (SD) (range 1.00 to -3.00 D), 0.37 +/- 0.64 D (range 1.68 to -1.49 D), and 
      0.44 +/- 1.13 D (range 1.63 to -3.50 D), respectively. The Pearson correlation
      coefficients between MR and Tracey values and between MR and AR values were high
      (r = 0.895 and r = 0.875, respectively; both P < .0001). However, the mean
      difference between the Tracey and MR values was 1.13 +/- 0.48 D (range 2.45 to 
      0.06 D) (P < .001). The mean cylindrical differences between MR and Tracey and
      between MR and AR were 0.03 +/- 0.51 D (range 1.22 to -1.07 D) (P = .709) and 
      0.30 +/- 0.62 D (range 0.50 to -2.25 D) (P = .003), respectively. Power vector
      analysis revealed difference vectors of -0.16 x 60 between Tracey and MR and 
      0.22 x 87 between AR and MR. CONCLUSIONS: Spherical and cylindrical refractive
      data obtained with the Tracey system correlated well with those derived from MR;
      however, there was a mean spherical error of approximately 1.10 D. Further work
      is required to refine the accuracy and range of this device.

PMID- 11821211
TI  - Comparison of the pupil card and pupillometer in measuring pupil size.
AB  - PURPOSE: To determine the difference in pupil size measured with the Colvard
      pupillometer in mesopic and scotopic luminance and with the Rosenbaum pupil card
      in mesopic luminance between 2 examiners. SETTING: Michel Pop Clinics, Montreal,
      Quebec, Canada. METHODS: Two examiners used the Colvard pupillometer and the
      Rosenbaum card to measure pupil size in 58 eyes. The Colvard pupillometer was
      used in mesopic and scotopic light conditions. The Rosenbaum card was used in
      mesopic luminance only. Pupil size was evaluated with a 1.0 mm interval scale at
      the nearest half millimeter. RESULTS: For the 3 sets of data, the limits of
      agreement and coefficient of interrater repeatability were calculated and a 2 x 2
      factorial analysis of variance was performed. Because of interexaminer bias,
      measurements done in mesopic luminance with the Rosenbaum card were not
      statistically different from those with the Colvard pupillometer in scotopic
      luminance, although interrater repeatability of the Colvard pupillometer (0.8 mm)
      was superior to that of the Rosenbaum card (1.3 mm). CONCLUSIONS: Examiner bias
      was the greatest statistical bias in all sets of measures. Surgeons may want to
      opt for a "safe" limit of pupil size (ie, 0.5 to 0.8 mm greater than the measured
      size) when calculating optical zones in refractive surgery. Future devices for
      pupil measurement should be based on automatic adjustment sizing.

PMID- 11821212
TI  - Analysis of anterior and posterior corneal curvature changes using Orbscan
      technology in radial keratotomy eyes exposed to hypoxia.
AB  - PURPOSE: To study the changes in anterior and posterior corneal curvatures in
      radial keratotomy (RK) and normal eyes exposed to hypoxia using Orbscan (Bausch &
      Lomb) technology. SETTING: Department of Ophthalmology, Madigan Army Medical
      Center, Tacoma, Washington, USA. METHODS: At sea level, 11 RK subjects and 10
      control subjects were exposed to ocular surface hypoxia in 1 eye by filtering
      humidified, compressed 100% nitrogen (0% oxygen) through an airtight goggle
      system for 2 hours. The contralateral eye was exposed to humidified, compressed
      air (21% oxygen) simultaneously through the airtight goggle system. Orbscan
      analysis was performed in each subject before and immediately after gas exposure.
      This analysis included measurement of the anterior axial and posterior axial
      corneal curvatures as well as corneal pachymetry. RESULTS: In the RK eyes exposed
      to 100% nitrogen gas, there was a statistically significant flattening in the
      anterior axial corneal curvature (P = .0012) and in the posterior axial corneal
      curvature (P = .0067). Radial keratotomy and control eyes exposed to air and
      control eyes exposed to 100% nitrogen gas demonstrated no statistically
      significant change in the anterior axial or posterior axial corneal curvature.
      CONCLUSIONS: Corneal hypoxia induced a statistically significant flattening in
      the anterior axial and posterior axial corneal curvatures in eyes that had had
      RK. There was no significant change in these curvatures in RK eyes exposed to air
      and in control eyes exposed to air or 100% nitrogen gas.

PMID- 11821213
TI  - Toric intraocular lens implantation: 100 consecutive cases.
AB  - PURPOSE: To evaluate the first 100 consecutive cases of toric posterior chamber
      silicone intraocular lens (IOL) implantation by 2 community-based
      ophthalmologists. SETTING: Two private practices in western Virginia, USA.
      METHODS: Data on the first 100 consecutive toric IOL implantations in 81 patients
      were collected in a prospective manner. Cataract surgery was performed using
      topical anesthesia and phaco-chop, phaco-flip, or divide-and-conquer
      phacoemulsification. A Staar AA4203TF or AA4203TL IOL with a 2.00 diopter (D) or
      3.50 D toric power was implanted using a lens injector. After the viscoelastic
      material was removed, the IOL was rotated to the desired orientation. The IOL
      orientation was assessed postoperatively at 1 day, 1 to 2 weeks, and the last
      visit. The mean follow-up was 23 weeks +/- 17 (SD). RESULTS: The IOLs performed
      in a predicable fashion. The mean astigmatism correction with IOLs within 15
      degrees of the intended axis was 1.62 D with the 2.00 D IOL and 2.86 D with the
      3.50 D IOL. Eleven patients had IOLs that were rotated more than 15 degrees away
      from the intended axes; in 3, the astigmatism was worse than preoperatively. The
      mean preoperative refractive and keratometric astigmatism was 2.48 D and 2.11 D,
      respectively. The mean postoperative astigmatism was 0.87 D and 2.05 D,
      respectively. At the last follow-up, half the patients had residual refractive
      astigmatism of 0.50 D or less and 45% had an uncorrected visual acuity of 20/30
      or better. Of postoperative patients with a 20/30 visual acuity with or without
      correction, 52% could see this well no correction. CONCLUSIONS: The results show
      that toric IOL implantation can help an estimated 20% of patients with
      astigmatism achieve good vision and a reduced need for distance spectacles. If
      IOL rotation occurs, it is usually during the first week and can be remedied by
      repositioning the IOL at 1 week.

PMID- 11821214
TI  - Risk factors for secondary membrane formation after removal of pediatric
      cataract.
AB  - PURPOSE: To evaluate the incidence of secondary membrane formation, factors that
      lead to its development, and the frequency of procedures to treat these membranes
      in children after cataract surgery. SETTING: Department of Pediatric
      Ophthalmology, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA.
      METHODS: Clinical records of 152 patients (190 eyes) who had cataract extraction
      between January 1986 and 1996 were reviewed retrospectively. The mean follow-up
      was 6 years (range 2 to 13 years). Cataract surgery was performed through a
      limbal incision in all cases. Twenty-eight eyes had a primary posterior
      capsulectomy, and 120 eyes had posterior capsulectomy combined with an anterior
      vitrectomy. In 42 eyes, the posterior capsule was left intact. Nineteen eyes
      received a primary intraocular lens (IOL), 15 eyes received a secondary IOL, and
      156 eyes were rehabilitated with spectacles or contact lenses. RESULTS: Seventy
      two eyes (37.9%) developed secondary membrane a mean of 8.9 months
      postoperatively (range 3 weeks to 53 months). Membranes occurred in 78.6% of eyes
      with an intact posterior capsule, 42.9% with posterior capsulectomy, and 22.5%
      with combined posterior capsulectomy and anterior vitrectomy. Secondary membrane
      formation was associated with not performing a posterior capsulectomy with
      anterior vitrectomy (P < .001) and the presence of a primary IOL (P < .001).
      Younger age at surgery increased the chance of secondary membrane formation in
      patients who had posterior capsulectomy and anterior vitrectomy (P < .01).
      CONCLUSIONS: The younger the child at cataract surgery, the greater the risk of
      secondary membrane. Primary posterior capsulectomy combined with an anterior
      vitrectomy decreased but did not eliminate the incidence of secondary membrane.

PMID- 11821215
TI  - Retained intravitreal lens fragments after phacoemulsification: complications and
      visual outcome in vitrectomized and nonvitrectomized eyes.
AB  - PURPOSE: To evaluate the ocular complications and visual outcomes in
      vitrectomized and nonvitrectomized eyes with retained lens fragments after
      phacoemulsification. SETTING: Department of Neurological, Psychiatric, and
      Ophthalmological Sciences, University of Padua, Padua, Italy. METHODS: This
      prospective nonrandomized study comprised 36 consecutive patients with retained
      intravitreal lens fragments after phacoemulsification. Eighteen eyes had a pars
      plana vitrectomy (Group 1), and 18 eyes (Group 2) were treated with medication
      only. Intraocular pressure (IOP), intraocular inflammation, cystoid macular edema
      (CME), and best corrected visual acuity (BCVA) were evaluated 1, 3, and 6 months
      postoperatively. RESULTS: Ophthalmoscopy and B-scan echography showed that the
      lens fragments were significantly larger in Group 1 than in Group 2 (P < .03). An
      uncontrollable IOP rise and inflammation prompted an early vitrectomy in 11 eyes
      in Group 1. At the 6-month follow-up, the IOP with medications was acceptable in
      2 and 5 eyes in Group 1 and Group 2, respectively. Intraocular inflammation was
      no longer detectable 1 month after vitrectomy but persisted during the entire
      follow-up in Group 2. At 3 months, 5 eyes in Group 1 and 13 in Group 2 had CME
      and at 5 months, 3 eyes and 1 eye, respectively, had CME. The difference between
      groups was significant at both follow-ups (P < .05). Three retinal detachments, 1
      before and 2 after vitrectomy, occurred in Group 1. The mean BCVA in Group 1 was
      better than in Group 2 during the entire follow-up; however, the difference was
      significant at 3 months only (P < .5). At 6 months, 94.4% in Group 1 and 83.2% in
      Group 2 had a BCVA of 20/50 or better and 66.6% and 55.5%, respectively, attained
      at least 20/30. CONCLUSIONS: Intraocular inflammation, increased IOP, and CME
      were major complications in nonvitrectomized eyes after phacoemulsification;
      retinal detachment occurred in 2 vitrectomized eyes. In eyes with intravitreal
      lens fragments after phacoemulsification, vitrectomy can yield faster visual
      rehabilitation and better quality of vision. Conservative management is feasible
      at the price of long-term intraocular inflammation and slower restoration of
      comparable visual function.

PMID- 11821216
TI  - Cataract surgery in patients with Behcet's disease.
AB  - PURPOSE: To evaluate the outcomes and complications of cataract surgery in
      patients with Behcet's disease. SETTING: Department of Ophthalmology, Hacettepe
      University School of Medicine, Ankara, Turkey. METHODS: Thirty-three eyes of 26
      patients with Behcet's disease that had extracapsular cataract surgery between
      January 1993 and July 1999 were analyzed retrospectively. The mean age of the
      patients was 38.9 years (range 20 to 54 years). The mean postoperative follow-up
      was 22.9 months (range 6 to 66 months). RESULTS: Extracapsular cataract
      extraction (ECCE) was performed in 22 eyes with and in 6 eyes without intraocular
      lens (IOL) implantation. Phacoemulsification with IOL implantation was performed
      in 5 eyes. Postoperatively, the visual acuity was better in 29 eyes (87.8%) and
      was 0.5 or better in 14 eyes (42.4%). Posterior segment complications of Behcet's
      disease, mainly optic atrophy and macular alterations from preoperative
      inflammatory episodes, restricted final acuity. No significant difference was
      detected in postoperative inflammation among the types of surgery; that is, ECCE,
      ECCE with IOL implantation, and phacoemulsification with IOL implantation. A
      neodymium:YAG laser posterior capsulotomy was performed in 3 cases. CONCLUSIONS:
      In patients with Behcet's disease, inflammation after extracapsular surgery was
      mild when surgery was performed after at least 3 months of no inflammatory signs.
      The results show that the outcomes of extracapsular cataract surgery mainly
      depend on the degree of preoperative posterior segment involvement.

PMID- 11821217
TI  - Naproxen ophthalmic solution to manage inflammation after phacoemulsification.
AB  - PURPOSE: To explore the efficacy and safety of 2 concentrations (0.1% and 0.2%)
      of sodium naproxen ophthalmic solution in controlling ocular inflammation in
      patients having phacoemulsification and intraocular lens implantation. SETTING:
      Service d'Ophtalmologie La Pitie' and Centre Ophtalmologique, Paris, and Clinique
      Sourdille, Nantes, France; Department of Ophthalmology, University of Lausanne,
      Switzerland. METHODS: One hundred one patients were randomly treated with
      naproxen 0.1%, naproxen 0.2%, or diclofenac 0.1% 3 times a day for 30 days
      starting the day before surgery. Postsurgical ocular inflammation was measured
      after 1, 10, and 30 days using the Kowa FC-1000 laser flare-cell meter and a
      conventional slitlamp biomicroscope. Safety parameters were evaluated at the same
      visits. RESULTS: Naproxen 0.2% ophthalmic solution and diclofenac 0.01% were
      comparable in controlling postsurgical inflammation. The naproxen was well
      tolerated. No serious adverse events occurred during the study. CONCLUSIONS:
      These preliminary results suggest that naproxen ophthalmic solution may be
      effectively and safely used to control inflammation after uneventful
      phacoemulsification. Because of the limited number of patients, larger studies
      are needed to confirm these results.

PMID- 11821218
TI  - Scanning electron microscopic evaluation of the surface characteristics of 4
      microkeratome systems in human corneas.
AB  - PURPOSE: To evaluate the surface characteristics of keratectomy specimens created
      with 4 microkeratomes by scanning electron microscopy (SEM). SETTING: Two
      university institutions. METHODS: Keratectomies were performed in 10 fresh,
      unfrozen human eyes with 1 of 4 microkeratomes: the Draeger rotary microkeratome
      (Storz Instruments), the Universalkeratome (Phoenix), the Automated Corneal
      Shaper (Bausch & Lomb), or the Hansatome (Bausch & Lomb). The beds and edges of
      the keratectomy specimens were then examined by SEM. Standardized photographs
      were taken, and the surface and cut-edge characteristics of the keratectomies
      were compared. RESULTS: Irregularities were noted in the cut edges of Bowman's
      membrane and the surface of the keratectomy beds with all instruments. The
      irregularities were most prominent in corneas cut with the Draeger instrument and
      least prominent in those cut with the Universalkeratome. The serrations in
      Bowman's membrane and the irregularities in the keratectomy bed appeared to be
      related to the blade movement in oscillating blade instruments. CONCLUSIONS: All
      4 microkeratomes caused some degree of surface irregularity. The Draeger
      microkeratome, which uses a continuously rotating blade, resulted in the greatest
      number of Bowman's membrane serrations and irregularities in the keratectomy bed.
      The tissue irregularities may be related to the development of pressure ridges
      ahead of the blade. In instruments that use an oscillating blade, chatter marks
      appear to be related to the reciprocating movement of the blade as it travels
      across the corneal stroma.

PMID- 11821219
TI  - Anterior capsule dyes and labeled viscoelastic solutions to enhance contrast in
      EAS-1000 Scheimpflug images.
AB  - PURPOSE: To enhance contrast in images produced by the EAS-1000 to facilitate
      evaluation of the rheological properties of viscoelastic substances during
      simulated cataract surgery. SETTING: Department of Preclinical Ophthalmology,
      Scientific Affairs, Pharmacia AB, Uppsala, Sweden. METHODS: Cataract surgery was
      performed in 200 fresh porcine cadaver eyes and documented by EAS-1000
      Scheimpflug photography. The light scattering caused by anterior capsule dyes,
      labeled irrigation solutions, and labeled viscoelastic solutions was
      statistically analyzed in the images. RESULTS: Visualization by light scattering
      was significantly enhanced by a fluorescein labeled viscoelastic solution and by
      an eosin-Y- or phloxine-B-dyed capsule (P < .05). A side effect of eosin Y and
      phloxine B was that the capsule became fragile, making it difficult to perform a
      continuous curvilinear capsulorhexis. CONCLUSIONS: Fluorescein-labeled
      viscoelastic solutions are recommended to enhance contrast in the images when
      retention capacity is evaluated. Light scattering from capsule dyeing facilitated
      anterior chamber depth measurements in the images.

PMID- 11821220
TI  - Refractive Surgery Survey 2001.
AB  - In February 2001, a questionnaire on the practice of refractive surgery was sent
      worldwide to all 8196 members of the American Society of Cataract and Refractive
      Surgery; 1511 responses (18.4%) were received. Although laser in situ
      keratomileusis (LASIK) was the most common refractive procedure reported, phakic
      intraocular lenses, clear lens extraction, and photorefractive keratectomy were
      also widespread. Nineteen percent of the respondents said they had had refractive
      surgery, and that group reported performing significantly more procedures than
      those who had not had a refractive procedure (P < .0001). The most common
      complication of LASIK was dry eyes, occurring in more than half of the cases in
      one fourth of the practices; however, only 30% of surgeons said they perform a
      Schirmer test before surgery. High-volume surgeons reported seeing fewer cases of
      flap striae (P = .002) and slipped flaps (P = .02) than low-volume surgeons.
      Seventy-seven percent said that wavefront LASIK ablation will increase the
      quality of vision and of those already performing wavefront ablation, 92% stated
      they believe it will improve outcomes.

PMID- 11821221
TI  - Progression to end-stage glaucoma after laser in situ keratomileusis.
AB  - We describe 2 patients, one a glaucoma suspect because of family history and the
      other with juvenile glaucoma. Both patients developed complications after laser
      in situ keratomileusis that required frequent topical steroids, leading to
      steroid-induced glaucoma. In both cases, corneal edema from the acute rise in
      intraocular pressure (IOP) caused inaccurate IOP measurement by standard methods.
      The inability to recognize glaucoma early may have resulted in significant
      irreversible vision loss.

PMID- 11821223
TI  - Acanthamoeba keratitis after photorefractive keratectomy.
AB  - A 37-year-old women developed severe suppurative keratitis immediately after
      having photorefractive keratectomy in her left eye. The keratitis was
      unresponsive to intensive topical antibiotic agents and topical and systemic
      steroids. Although the differential diagnosis included nonmicrobial and fungal
      keratitis, the clinical course and confocal microscopy suggested, and subsequent
      histopathologic examination confirmed, a diagnosis of Acanthamoeba keratitis. The
      amebic contamination probably resulted from exposure of the deepithelialized
      cornea to contaminated freshwater in a northern Wisconsin marsh. This case
      emphasizes the importance of encouraging patients with epithelial defects and
      bandage soft contact lenses to avoid exposure to contaminated freshwater until
      reepithelialization is complete.

PMID- 11821222
TI  - Imaging of posterior chamber phakic intraocular lens by optical coherence
      tomography.
AB  - We demonstrate the applicability of optical coherence tomography to visualize the
      distance between the intraocular lens (IOL) and the lens capsule (lens vault)
      after implantation of the Staar Collamer posterior phakic IOL, also known as the
      implantable contact lens (ICL). Maintaining a substantial lens vault may be
      important to avoid cataract formation, but the lens vault was found to change
      over time; changes in accommodation and pupil size have also been noted. Optical
      coherence tomography allows precise assessment of the anatomic relationship
      between the ICL and the crystalline lens in a noncontact, noninvasive manner,
      permitting dynamic monitoring of changes in accommodation and pupil size.

PMID- 11821224
TI  - Correction of the Pulfrich phenomenon by surgery and laser.
AB  - We describe 2 patients who presented with asymmetrical media changes and a
      spontaneous Pulfrich phenomenon. In the first case, the phenomenon was due to
      cataract formation and an interocular latency difference of 1.49 ms +/-0.07 (SD)
      was found. After cataract surgery, the symptoms resolved and no interocular
      latency difference could be measured. In the second case, the phenomenon was
      caused by posterior capsule opacification and an interocular latency difference
      of 1.16 +/- 0.08 ms was found. The symptoms were alleviated and no interocular
      latency difference could be measured after a neodymium:YAG laser capsulotomy was
      performed. The symptomatology of the Pulfrich phenomenon is often difficult for
      patients to explain. Clinicians should be aware of the phenomenon with cataract
      patients.

PMID- 11821225
TI  - Acute comitant esotropia after cataract surgery.
AB  - A 52-year-old woman developed comitant esotropia after cataract surgery. The
      ocular history was significant for accommodative esotropia; preoperatively, she
      manifested peripheral fusion with central suppression. Immediately
      postoperatively, the patient was diplopic with comitant esotropia and was treated
      with extraocular muscle surgery. The appearance of horizontal strabismus after
      cataract surgery in patients with a history of accommodative esotropia,
      especially those with subnormal binocularity, is a possible complication that
      should be discussed with the patient.

PMID- 11821226
TI  - Histopathology of anterior lens capsules in vitrectomized eyes with tamponade by
      silicone oil.
AB  - Histopathologic examination and immunohistochemistry for collagen type V were
      performed on residual anterior lens capsules of vitrectomized eyes (2 patients)
      that had been tamponaded with silicone oil. Many spaces, presumably occupied by
      oil droplets, were observed in connective tissue accumulations beneath the
      capsules. Immunoreactivity in the extracellular matrix for collagen type V was
      most marked adjacent to these spaces. These silicone droplets may delay capsule
      healing as collagen type V indicates immature connective tissue.

PMID- 11821229
TI  - A modified ex vivo human whole blood model of infection for studying the
      pathogenesis of Neisseria meningitidis during septicemia.
AB  - For the purpose of establishing a model to study host-bacteria interaction and
      virulence mechanisms of Neisseria meningitidis during the septic phase of disease
      a modified human whole blood model of infection is proposed. Compared to
      published whole blood models the current model was modified with respect to the
      initial number of viable bacteria (10(4) cfu ml(-1)), the anticoagulant used and
      the incubation time. The results obtained after incubation of a number of human
      blood samples from healthy volunteers for 24 h with serogroup B meningococci were
      in good agreement with findings reported from patients who suffered severe
      meningococcal disease.

PMID- 11821230
TI  - Mycoplasma bovis induces apoptosis of bovine lymphocytes.
AB  - We report Mycoplasma bovis induces apoptotic death of bovine lymphocytes. Using
      flow cytometry analyzed propidium iodide inclusion we observed a loss in viable
      lymphocytes upon incubation of freshly isolated bovine PBMCs with M. bovis. The
      use of annexin V staining as well as TUNEL assays corroborated these findings. In
      addition, these assays indicated that the M. bovis induced lymphocyte death is
      apoptotic in nature. Subsequent experiments demonstrated that the prokaryotic
      protein production inhibitor chloramphenicol inhibited lymphocyte death induced
      by M. bovis, showing that M. bovis protein production is necessary for the
      induction of lymphocyte death, and that the death is not dependent upon the
      addition of apoptotic inducers as shown with other mycoplasmas. We also show that
      M. bovis is different from other bovine mycoplasmas (both pathogenic and non
      pathogenic) with regards to this characteristic.

PMID- 11821231
TI  - Inhibition of binding of Helicobacter pylori to the glycolipid receptors by
      probiotic Lactobacillus reuteri.
AB  - We examined the competition of binding of Lactobacillus reuteri and Helicobacter
      pylori to gangliotetraosylceramide (asialo-GM1) and sulfatide which are putative
      glycolipid receptor molecules of H. pylori, and identified a possible sulfatide
      binding protein of the L. reuteri strain. Among nine L. reuteri strains, two
      (JCM1081 and TM105) were shown to bind to asialo-GM1 and sulfatide, and to
      inhibit binding of H. pylori to both glycolipids by a thin layer chromatogram
      overlay assay using biotin-labeled bacterial cells. The extract from the
      bacterial cells of strain TM105 with several detergents, including octyl beta-D
      glucopyranoside, retained binding to both glycolipids and also inhibited H.
      pylori binding, suggesting that a binding inhibitor(s) is associated with the
      bacterial cell surface. When the cell extract was applied to the agarose gel
      immobilized galactose 3-sulfate corresponding to the structure of sugar moieties
      of sulfatide, an approximately 47-kDa protein was found to bind to the gel. This
      observation strongly suggested that inhibition by selected L. reuteri strains
      help to prevent infection in an early stage of colonization in H. pylori and
      proposed that L. reuteri strains sharing glycolipid specificity with H. pylori
      have a potential as probiotics.

PMID- 11821232
TI  - Dysregulation of interleukin-10 and interleukin-12 are involved in the reduced
      host resistance to Listeria monocytogenes infection in alymphoplastic aly mutant
      mice.
AB  - The aly is a unique spontaneous autosomal recessive mutation in mice that causes
      a systemic defect of lymph nodes and Peyer's patches and disorganized splenic and
      thymic structures with immunodeficiency. Our previous study demonstrated that
      resistance to Listeria monocytogenes infection and interferon-gamma (IFN-gamma)
      production are attenuated in the mutant mice. In this study, we investigated the
      mechanism of decrease in antilisterial resistance and IFN-gamma production in aly
      mice. Interleukin (IL)-12 production in response to heat-killed L. monocytogenes
      (HK-LM) was decreased but IL-10 production was increased in aly/aly macrophage
      cultures, compared with those in aly/+ macrophages. Nonadherent cells and
      macrophages obtained from the spleens of naive aly/+ mice and aly/aly mice were
      reconstituted and stimulated with HK-LM. IFN-gamma production was markedly
      decreased when macrophages derived from aly/aly mice were used. IFN-gamma
      production in aly/aly spleen cell cultures was recovered in the presence of anti
      IL-10 monoclonal antibody (mAb) or recombinant IL-12. When aly/+ mice and aly/aly
      mice were injected with mAb against IL-10 or IL-12 p40, antilisterial resistance
      was inhibited by injection of anti-IL-12 p40 mAb, while anti-IL-10 mAb treatment
      augmented the resistance. Administration of anti-IFN-gamma mAb attenuated
      antilisterial resistance in aly/+ mice but not in aly/aly mice. The present
      results suggest that downregulation of IL-12 and upregulation of IL-10 in
      macrophages might be involved in the decrease in antilisterial resistance and IFN
      gamma production in aly/aly mice in addition to the structural defect in lymphoid
      organs. Moreover, the results predict that an IL-12-dependent and IFN-gamma
      independent mechanism may be also involved in the decrease in antilisterial
      resistance in aly/aly mice.

PMID- 11821233
TI  - O-Acetylation status of the capsular polysaccharides of serogroup Y and W135
      meningococci isolated in the UK.
AB  - At a time when tetravalent conjugate vaccines for meningococcal serogroups
      A/C/Y/W135 are being formulated the O-acetylation status of their respective
      capsular polysaccharides has not previously been studied in the UK for all
      components. Although this has been elucidated for serogroup C, little is known
      about the O-acetylation status of serogroups W135 and Y. Meningococcal serogroup
      W135 (n=181) and Y (n=90) isolates submitted to the PHLS Meningococcal Reference
      Unit in 1996, 2000 and 2001 were investigated for O-acetylation capsular status
      by dot blot assay. Eight per cent of W135 and 79% of Y isolates respectively were
      found to be O-acetylated with a similar distribution found in both carrier and
      case isolates. An increase in O-acetylated W135 isolates was noted between 2000
      (0%) and 2001 (21%) which was not due to the introduction of the Hajj associated
      W135 (ET 37 complex; serosubtype P1.5,2) isolates, all of which were de-O
      acetylated. Although the biological relevance of O-acetylation status is unknown
      for these serogroups, an understanding of O-acetylation status of the respective
      polysaccharides may provide useful insights into the optimal vaccine formulation.

PMID- 11821234
TI  - Mitochondrial alterations precede Bordetella pertussis-induced apoptosis.
AB  - Bordetella pertussis, the causative agent of whooping cough in humans, secretes a
      number of toxins, including adenylate cyclase-hemolysin (AC-Hly), and induces
      macrophage apoptosis. We investigated the effects of B. pertussis on
      mitochondrial membrane potential (deltapsim) and ATP levels, as possible
      determinants of cell death. Using the fluorescent probe JC-1, we found that
      infection of human monocytes by B. pertussis lead to a disruption in host-cell
      deltapsim. deltapsim alterations were preceded by a massive increase in cyclic
      AMP, a moderate decrease in ATP, and was independent from oxidative stress. These
      changes were observed when human monocytes were infected by the parental B.
      pertussis 18323 but not when infected by the mutants deficient in the expression
      of AC-Hly. Exposure of human monocytes to purified AC-Hly induced changes
      comparable to those observed with the B. pertussis parental strain. Our results
      provide a mechanistic relationship between AC-Hly, ATP, and deltapsim disruption
      in the cascade of events leading to B. pertussis-induced apoptosis.

PMID- 11821235
TI  - Development of hematogenous pneumococcal meningitis in adult mice: the role of
      TNF-alpha.
AB  - Bacterial penetration across the blood-brain barrier (BBB) into the central
      nervous system is the first step in development of meningitis. The role of tumor
      necrosis factor-alpha (TNF-alpha) in the penetration process was examined with
      peripheral infection of Streptococcus pneumoniae type 6. After intraperitoneal
      infection of S. pneumoniae type 6, the BBB opening was increased continuously
      from 6 h and the mice died of septic shock within 36 h due to bacterial
      overgrowth. The bacteria crossed the BBB and began to deposit in brain at 6 h
      post infection. There was strong staining of TNF-alpha on blood vessels of brain
      from 6 h to 24 h post infection. Anti-TNF-alpha antibody blocked both the BBB
      opening and the entrance of circulatory S. pneumoniae type 6 into brain,
      indicating that TNF-alpha played an important role in controlling the opening of
      BBB. Furthermore, an adult murine model of hematogenous pneumococcal meningitis
      was developed that is based on opening of the BBB by TNF-alpha and controlling
      the degree of bacteremia by cefazolin antibiotic. In conclusion, hematogenous
      meningitis developed as TNF-alpha initiated BBB opening, peripheral bacteria
      entered into the brain and formed bacterial emboli, and then progressed to
      meningitis.

PMID- 11821236
TI  - Priming and activation of mouse macrophages by trehalose 6,6'-dicorynomycolate
      vesicles from Corynebacterium glutamicum.
AB  - Vesicles consisting of pure trehalose dicorynomycolate (TDCM), the
      corynebacterial analog of the most studied mycobacterial glycolipid 'cord
      factor', were isolated from Corynebacterium glutamicum cells by mild detergent
      treatment; these induced in vivo a macrophage priming similar to that obtained
      with mycobacterial-derived trehalose dimycolate. In vitro, both TDCM and
      bacterial lipopolysaccharide (LPS) induced in macrophages the production of
      nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha), endotoxin
      tolerance, and were primed for an enhanced secondary NO response to LPS.
      Interferon-gamma pretreatment did not influence the LPS-induced TNF-alpha
      response, but considerably increased the TDCM-induced response.

PMID- 11821237
TI  - Differential microbial clearance and immunoresponse of Balb/c (Nramp1
      susceptible) and DBA2 (Nramp1 resistant) mice intracerebrally infected with
      Mycobacterium bovis BCG (BCG).
AB  - In mice, the gene encoding Nramp1 (natural resistance-associated protein 1)
      exists in two allelic forms, differing for a point mutation. According to Nramp1
      genotype, extensive literature documents a clear-cut distinction of inbred
      strains in two non-overlapping groups that phenotypically express resistance
      (Nramp1r) and susceptibility (Nramp1s) to systemic infections. Here, we provide
      evidence that Nramp1r (DBA/2) and Nramp1s (Balb/c) mice differently handle
      intracerebral infection with Mycobacterium bovis BCG. Distinct trends of
      microbial clearance from the brain and also different patterns of local immune
      responses occur, thus arguing on the involvement of Nramp1 gene product on the
      accomplishment of cerebral anti-mycobacterial defenses.

PMID- 11821238
TI  - Phase variable restriction-modification systems in Moraxella catarrhalis.
AB  - A repetitive DNA motif was used as a marker to identify novel genes in the
      mucosal pathogen Moraxella catarrhalis. There is a high prevalence of such
      repetitive motifs in virulence genes that display phase variable expression. Two
      repeat containing loci were identified using a digoxigenin-labelled 5'-(CAAC)6-3'
      oligonucleotide probe. The repeats are located in the methylase components of two
      distinct type III restriction-modification (R-M) systems. We suggest that the
      phase variable nature of these R-M systems indicates that they have an important
      role in the biology of M. catarrhalis.

PMID- 11821239
TI  - Kinetics of cytokine expression in mice with invasive aspergillosis: lethal
      infection and protection.
AB  - Aspergillus fumigatus causes lethal invasive aspergillosis in cortisone-treated
      mice while immunized mice are protected. Kinetics of interferon (IFN)-gamma,
      tumor necrosis factor-alpha, interleukin (IL)-12p40, IL-4 and IL-10 expression
      were assessed by reverse transcription-PCR in the spleen and lungs of mice. After
      immunization, mice were protected from otherwise lethal infection, with
      concomitant high expression levels of IFN-gamma early in the lungs and later in
      the spleen. In the lethal infection model cortisone-treated infected mice
      presented high expression levels of IL-10 in the spleen and in the lungs.
      Immunocompetent mice were able to control the disease and presented earlier
      expression of IL-12p40 and IFN-gamma in lungs and spleen. These results confirm
      the importance of Th1 dependent immunity against invasive aspergillosis.

PMID- 11821240
TI  - Fluoride modifies adhesion of Streptococcus pyogenes.
AB  - Streptococcus pyogenes grown in the presence of subinhibitory concentrations of
      sodium fluoride had a diminished ability, compared to control cells, to adhere to
      buccal cells, collagen, fibronectin, and laminin. In addition, sodium fluoride
      was a competitive inhibitor of streptococcal adhesion to collagen and
      fibronectin, but not laminin. It is suggested that sodium fluoride may be useful
      in therapy or prophylaxis in infections involving group A streptococci.

PMID- 11821241
TI  - Obesity may increase the incidence of asthma in women but not in men:
      longitudinal observations from the Canadian National Population Health Surveys.
AB  - To investigate the possibility of gender specificity for the effect of body mass
      index (BMI) on development of asthma, the authors used the longitudinal data from
      the first and second cycles of the National Population Health Survey, conducted
      in Canada in 1994-1995 and 1996-1997, respectively. Data from 9,149 subjects
      (4,266 men and 4,883 women) aged 20-64 years who reported no asthma at baseline
      were used in this analysis. The 2-year cumulative incidence of asthma was
      estimated by using a bootstrap procedure to take sampling weights and design
      effects into account. During the 2-year study period, 1.6% of the men and 2.9% of
      the women developed asthma. Average changes in body weight and BMI over the 2
      year observation period were relatively small and were not associated with asthma
      incidence. However, baseline BMI was a significant predictor for asthma incidence
      in women. The adjusted odds ratio for women whose baseline BMI was at least 30.0
      kg/m(2) versus 20.0-24.9 kg/m(2) was 1.9 (95% confidence interval: 1.1, 3.4),
      whereas the corresponding odds ratio of 1.1 (95% confidence interval: 0.3, 3.6)
      for men was not significantly different from unity. The authors concluded that
      obesity was related to development of asthma in women but not in men.

PMID- 11821242
TI  - Invited commentary: obesity and asthma--new perspectives, research needs, and
      implications for control programs.

PMID- 11821244
TI  - Impact of preeclampsia and gestational hypertension on birth weight by
      gestational age.
AB  - The predominant etiologic theory of preeclampsia is that reduced uteroplacental
      perfusion is the unique pathogenic process in the development of preeclampsia.
      Decreased uteroplacental blood flow would result in lower birth weights. To date,
      no study has assessed the effect of preeclampsia on birth weight by gestational
      age. Thus, the authors conducted a retrospective cohort study based on 97,270
      pregnancies that resulted in delivery between 1991 and 1996 at 35 hospitals in
      northern and central Alberta, Canada. Differences in mean birth weight between
      women with preeclampsia and normotensive women ranged from -547.5 g to 239.5 g
      for gestational age categories ranging from < or = 32 weeks to > or = 2 weeks.
      The birth weights were statistically significantly lower among mothers with
      preeclampsia who delivered at < or = 37 weeks, with an average difference of 
      352.5 g. However, the birth weights were not lower among preeclamptic mothers who
      delivered after 37 weeks (average difference of 49.0 g). In Alberta, 61.2% of
      preeclamptic patients gave birth after 37 weeks of gestation. The authors
      conclude that babies born to mothers with preeclampsia at term have fetal growth
      similar to that of babies born to normotensive mothers. This finding does not
      endorse the currently held theory that reduced uteroplacental perfusion is the
      unique pathophysiologic process in preeclampsia.

PMID- 11821245
TI  - Differing intergenerational birth weights among the descendants of US-born and
      foreign-born Whites and African Americans in Illinois.
AB  - The authors analyzed Illinois vital records to determine the intergenerational
      birth weight patterns among the descendants of US-born and foreign-born White and
      African-American women. Among the descendants of the generation 1 US-born White
      women (n = 91,061), generation 3 females had a birth weight 65 g more than that
      of their generation 2 mothers (p < 0.0001); generation 3 infants had a 10% lower
      moderately low birth weight (1,500-2,499 g) rate than did their generation 2
      mothers: 5.0% versus 5.5% percent, respectively (relative risk = 0.9, 95%
      confidence interval: 0.9, 0.9). Among the descendants of generation 1 European
      born White women (n = 3,339), generation 3 females had a birth weight 45 g more
      than that of their generation 2 mothers (p < 0.0001). Among the descendants of
      generation 1 US-born African-American women (n = 31,699), generation 3 females
      had a birth weight 17 g more than that of their generation 2 mothers (p < 0.001).
      Among the descendants of generation 1 African/Caribbean-born women (n = 104),
      generation 3 females had a birth weight 57 g less than that of their generation 2
      mothers; generation 3 females had a 40% greater moderately low birth weight rate
      than did their generation 2 mothers: 9.6% percent versus 6.7% percent (relative
      risk = 1.4, 95% confidence interval: 0.6, 3.6). Maternal age and marital status
      did not account for the birth weight trends. The authors conclude that the
      expected intergenerational rise in birth weight does not occur among the direct
      female descendants of foreign-born African-American women.

PMID- 11821246
TI  - Infertility, fertility drugs, and ovarian cancer: a pooled analysis of case
      control studies.
AB  - Controversy surrounds the relations among infertility, fertility drug use, and
      the risk of ovarian cancer. The authors pooled interview data on infertility and
      fertility drug use from eight case-control studies conducted between 1989 and
      1999 in the United States, Denmark, Canada, and Australia. Odds ratios and 95%
      confidence intervals were calculated, adjusting for age, race, family history of
      ovarian cancer, duration of oral contraception use, tubal ligation, gravidity,
      education, and site. Included in the analysis were 5,207 cases and 7,705
      controls. Among nulligravid women, attempts for more than 5 years to become
      pregnant compared with attempts for less than 1 year increased the risk of
      ovarian cancer 2.67-fold (95% confidence interval (CI): 1.91, 3.74). Among
      nulliparous, subfertile women, neither any fertility drug use (odds ratio (OR) =
      1.60, 95% CI: 0.90, 2.87) nor more than 12 months of use (OR = 1.54, 95% CI:
      0.45, 5.27) was associated with ovarian cancer. Fertility drug use in nulligravid
      women was associated with borderline serous tumors (OR = 2.43, 95% CI: 1.01,
      5.88) but not with any invasive histologic subtypes. Endometriosis (OR = 1.73,
      95% CI: 1.10, 2.71) and unknown cause of infertility (OR = 1.19, 95% CI: 1.00,
      1.40) increased cancer risk. These data suggest a role for specific biologic
      causes of infertility, but not for fertility drugs in overall risk for ovarian
      cancer.

PMID- 11821247
TI  - Interaction of waist/hip ratio and family history on the risk of hormone receptor
      defined breast cancer in a prospective study of postmenopausal women.
AB  - The authors previously reported an interaction of waist/hip ratio and family
      history on the risk of breast cancer in the Iowa Women's Health Study. Here they
      reexamine this association based on 9 additional years of follow-up, stratifying
      on tumor receptors for estrogen and progesterone. Data on risk factors and family
      history of breast cancer were ascertained in 1986. The occurrences of breast
      cancer and estrogen receptor/progesterone receptor were determined through the
      Iowa Surveillance, Epidemiology, and End Results' registry. Rate ratios were
      elevated with increasing weight and body mass index and decreasing body mass
      index at age 18 years, but they did not vary by family history. There was no
      association with height, waist circumference, or waist/hip ratio. A linear trend
      of increasing risk with increasing waist/hip ratio was observed among family
      history-positive women (p = 0.06) but not among family history-negative women (p
      = 0.87). This apparent interaction (p = 0.09) was examined by estrogen receptor
      or progesterone receptor status. When stratified on family history and estrogen
      receptor, no clear patterns were evident. In contrast, family history-positive
      women in the upper quintile of the waist/hip ratio were at 2.2-fold greater risk
      of progesterone receptor-negative tumors compared with those in the lowest
      quintile (95% confidence interval: 0.9, 5.8). Thus, the previously reported
      interaction between family history and waist/hip ratio is still (weakly) evident
      and appears to reflect risk for progesterone receptor-negative tumors.

PMID- 11821248
TI  - Fatal crashes among older drivers: decomposition of rates into contributing
      factors.
AB  - This study selected US drivers aged 55 years or older who were involved in fatal
      crashes in 1990 and 1995 and explored factors that influenced their fatal crash
      involvement rate. The fatal crash involvement rate (risk of being involved in a
      fatal crash) can be thought of as the product of the crash fatality rate (risk of
      dying given a crash), the crash incidence density (risk of crash), and the
      exposure prevalence (amount of driving). Fatal crash involvement rates increased
      with age. The relative contributions of the crash incidence densities and
      exposure prevalences were greater than that of the crash fatality rates. The
      decomposition methodology was shown to be a useful method for investigating the
      potential benefit of crash prevention interventions aimed at different components
      of the fatal crash involvement rate.

PMID- 11821249
TI  - Alcohol volume, drinking pattern, and cardiovascular disease morbidity and
      mortality: is there a U-shaped function?
AB  - The health effects of a binge pattern of alcohol consumption have not been widely
      investigated. The objective of this study was to evaluate the cardiovascular
      consequences of binge drinking (consumption of eight or more drinks at one
      sitting) and usual (nonbinge) drinking in a longitudinal, population-based study.
      Data obtained from 1,154 men and women aged 18-64 years interviewed in Winnipeg,
      Manitoba, Canada, in 1990 and 1991 were linked to health care utilization and
      mortality records. Using an 8-year follow-up period, the authors performed
      separate Cox proportional hazards regression analyses for men and women on time
      to first event for physician visits, hospitalizations, and deaths due to coronary
      heart disease, hypertension, and other cardiovascular disease. Binge drinking
      increased the risk of coronary heart disease in both men (hazard ratio (HR) =
      2.26, 95% confidence interval (CI): 1.22, 4.20) and women (HR = 1.10, 95% CI:
      1.02, 1.18). It increased the risk of hypertension in men (HR = 1.57, 95% CI:
      1.04, 2.35) but not in women. Binge drinking had no effect on the risk of other
      cardiovascular disease. In contrast, usual drinking had significant
      cardioprotective effects in both men and women. Thus, the harmful effects of
      binge drinking on cardiovascular disease morbidity and mortality can be
      disaggregated from the protective effects of usual drinking at various levels of
      consumption.

PMID- 11821250
TI  - Possible relation of Tunisian pemphigus with traditional cosmetics: a multicenter
      case-control study.
AB  - Pemphigus is a severe, autoimmune, blistering disorder with a high incidence
      among young women in rural Tunisia. The authors investigated explanatory
      environmental factors. A multicenter case-control study was conducted
      prospectively from 1992 to 1996 in Tunisia. Sixty-eight incident female cases of
      pemphigus and 166 controls matched on age, hospital, and geographic area were
      included. Data collected concerned socioeconomic status, medical history, drug
      intakes, lifestyle, and environment. Several factors were significantly
      associated with pemphigus in multivariate logistic regression analyses:
      traditional cosmetics (odds ratio (OR) = 4.0, 95% confidence interval (CI): 1.1,
      14.8); Turkish baths (OR = 3.2, 95% CI: 1.4, 7.3); cutting up raw poultry (OR =
      5.1, 95% CI: 1.3, 19.4); contact with ruminants (OR = 2.7, 95% CI: 1.3, 5.8); and
      wasp, bee, and spider stings (OR = 3.1, 95% CI: 1.5, 6.4). A dose-dependent
      relation was observed for traditional cosmetics. All risks except insect bites
      were higher when analysis was restricted to younger women, the demographic group
      with higher incidence. The strength of the associations, the dose-dependent
      relation for traditional cosmetics, and the increase of risk estimates for
      younger women support a causal relation. Traditional cosmetics widely used by
      Tunisian women could play a major role in excess of cases of pemphigus.

PMID- 11821251
TI  - Rise in malaria incidence rates in South Africa: a small-area spatial analysis of
      variation in time trends.
AB  - Using Bayesian statistical models, the authors investigated spatial and temporal
      variations in small-area malaria incidence rates for the period mid-1986 to mid
      1999 for two districts in northern KwaZulu Natal, South Africa. Maps of spatially
      smoothed incidence rates at different time points and spatially smoothed time
      trends in incidence gave a visual impression of the highest increase in incidence
      occurring where incidence rates previously had been lowest. This was confirmed by
      conditional autoregressive models, which showed that there was a significant
      negative association between time trends and smoothed baseline incidence before
      the steady rise in caseloads began. Growth rates also appeared to be higher in
      the areas close to the Mozambican border. The main findings of this analysis were
      that: 1) the spatial distribution of the rise in malaria incidence is uneven and
      strongly suggests a geographic expansion of high-malaria-risk areas; 2) there is
      evidence of a stabilization of incidence in areas that had the highest rates
      before the current escalation of rates began; and 3) areas immediately adjoining
      the Mozambican border appear to have undergone larger increases in incidence, in
      contrast to the general pattern of low growth in the more northern, high-baseline
      incidence areas, but this was not confirmed by modeling. Smoothing of small-area
      maps of incidence and growth in incidence (trend) is important for interpretation
      of the spatial distribution of disease incidence and the spatial distribution of
      rapid changes in disease incidence.

PMID- 11821252
TI  - Bias in association studies resulting from gene-environment interactions and
      competing risks.
AB  - The etiology, particularly the genetic basis, of multifactorial late-onset
      diseases is the subject of many genetic epidemiologic studies. The authors' aim
      in this paper was to investigate the circumstances under which competing risks
      can lead to bias in studies of genetic susceptibility to late-onset diseases. The
      authors used a model built in an epidemiologic framework to show that when a
      genetic risk factor and an environmental risk factor interact to cause a frequent
      competing risk of death, the measure of the association between the disease under
      investigation and the genetic risk factor will be biased if the environmental
      risk factor is also associated with the latter disease and is omitted from the
      analysis. This is an example of confounding bias, and it is the consequence of an
      association between the genetic risk factor and the environmental risk factor
      that appears over time. Numerical examples show that under certain conditions
      this bias can be substantial. The authors present several patterns of association
      in favor of such a bias. Because competing risks of death are likely to be
      present in older subjects, researchers studying the etiology of late-onset
      diseases should be aware of the possibility of this bias.

PMID- 11821253
TI  - Estimating crude or common odds ratios in case-control studies with informatively
      missing exposure data.
AB  - In case-control studies, the crude odds ratio derived from a 2 x 2 table and the
      common odds ratio adjusted for stratification variables are staple measures of
      exposure-disease association. While missing exposure data are encountered in the
      majority of such studies, formal attempts to deal with them are rare, and a
      complete-case analysis is the norm. Furthermore, the probability that exposure is
      missing may depend on true exposure status, so the missing-at-random assumption
      is often unreasonable. In this paper, the authors present an adjustment to the
      usual product binomial likelihood to properly account for missing data.
      Estimation of model parameters without restrictive assumptions requires an
      additional data collection effort akin to a validation study. Closed-form results
      are provided to facilitate point and confidence interval estimation of crude and
      common odds ratios after properly accounting for informatively missing data.
      Simulations assess performance of the likelihood-based estimates and inferences,
      and they display the potential for bias in complete-case analyses. An example is
      presented to illustrate the approach.

PMID- 11821254
TI  - Reproducibility of a self-administered lifetime physical activity questionnaire
      among female college alumnae.
AB  - Recent epidemiologic evidence suggests that lifetime physical activity is an
      important factor in the development of many chronic diseases. The authors
      assessed the reproducibility of a self-administered physical activity
      questionnaire designed to assess the duration, frequency, and intensity of
      lifetime household and recreational activities. The study was conducted among 134
      female college alumnae from two colleges in western Massachusetts who were aged
      39-65 years in 1998. A modified version of the Historical Leisure Activity
      Questionnaire was used to assess physical activity over four prior age periods
      (menarche to 21 years and 22-34, 35-50, and 51-65 years). The questionnaire was
      administered to participants by mail twice 1 year apart. The intraclass
      correlation coefficients used to measure reproducibility were 0.82 for total
      lifetime physical activity, 0.80 for lifetime moderate-intensity activities, 0.86
      for lifetime vigorous-intensity activities, 0.87 for lifetime recreational
      activities, and 0.78 for lifetime household activities. Correlations were 0.73
      for total activity during the earliest prior age period (menarche to 21 years),
      0.70 for ages 22-34 years, 0.78 for ages 35-50 years, and 0.83 for ages 51-65
      years. These data indicate that this physical activity questionnaire is
      reproducible and provides a useful measure of average lifetime activity.

PMID- 11821255
TI  - Exogenous application of transforming growth factor beta 1 stimulates
      arteriogenesis in the peripheral circulation.
AB  - Increased expression of transforming growth factor beta1 (TGF-beta1) during
      collateral artery growth, as well as its numerous effects on
      monocytes/macrophages and the smooth muscle cell cycle and differentiation,
      suggest a modulating role for this growth factor during arteriogenesis. We
      studied the effects of exogenously applied TGF-beta1 on arteriogenesis as well as
      its interactions with monocytes, endothelial cells, and smooth muscle cells. In a
      New Zealand White (NZW) rabbit model of femoral artery ligation, increased
      expression of active TGF-beta1 was found around proliferating arteries in NZW
      rabbits. The exogenous application of TGF-beta1 led to an increase in both the
      number of visible collateral arteries as well as the conductance of the
      collateral circulation (4.0 +/- 0.5 ml/min/100 mmHg vs. 28.9 +/- 3.7 ml/min/100
      mmHg, P<0.05). Fluorescence activated cell sorting analysis showed an increase in
      the expression of the MAC-1 receptor in both rabbit and human monocytes after
      treatment with TGF-beta1 (control: 91.2 +/- 4.2/482 +/- 21.7; TGF-beta1 200 ng/ml
      193.9 +/- 6.7/ 675.5 +/- 25.7, P<0.05 for all differences). TGF-beta1 treated
      monocytes showed an increased endothelial adhesion and transmigration in
      transendothelial migration assays (5.75 +/- 0.63 x 10(5) vs. 10.11 +/- 0.04 x
      10(5), P<0.05). TGF-beta1 had no direct pro-angiogenic effect on human umbilical
      vein endothelial cells in a spheroid model of angiogenesis and inhibited the
      angiogenic effects of vascular endothelial growth factor.

PMID- 11821256
TI  - Molecular characterization of an acetylcholinesterase implicated in the
      regulation of glucose scavenging by the parasite Schistosoma.
AB  - Acetylcholinesterase (AChE) present on the surface of the trematode blood fluke
      Schistosoma has been implicated in the regulation of glucose scavenging from the
      host blood. Determination of the molecular structure and functional
      characteristics of this molecule is a crucial first step in understanding the
      novel function for AChE and in evaluating the potential of schistosome AChE as a
      target of new parasite control methods. We have determined the primary structure
      of acetylcholinesterase from Schistosoma haematobium. Immunolocalization studies
      confirmed that the enzyme was present on the parasite surface as well as in the
      muscle. The derived amino acid sequence possesses features common to
      acetylcholinesterases: the catalytic triad, six cysteines that form three
      intramolecular disulphide bonds, and aromatic residues lining the catalytic
      gorge. An unusual feature is that the fully processed native enzyme exists as a
      glycoinositol phospholipid (GPI)-anchored dimer, but the sequence of the
      C?terminus does not conform to the current consensus for GPI modification. The
      enzyme expressed in Xenopus oocytes showed conventional substrate specificity and
      sensitivity to established inhibitors of AChE, although it is relatively
      insensitive to the peripheral site inhibitor propidium iodide. Distinctions
      between host and parasite AChEs will allow the rational design of schistosome
      specific drugs and vaccines.

PMID- 11821257
TI  - Differentiation-specific alterations to glutathione synthesis in and hormonally
      stimulated release from human skeletal muscle cells.
AB  - Muscle atrophy and cachexia are associated with many human diseases. These
      catabolic states are often associated with the loss of glutathione (GSH), which
      is thought to contribute to the induction of oxidative stress within the muscle.
      Glutathione synthesis and secretary characteristics were studied in human
      skeletal muscle myoblasts and myotube-like cells derived from the myoblasts by
      growth factor restriction. Differentiation was associated with a shift in the
      sulfur amino acid precursor specificity for synthesis of GSH from cystine to
      cysteine, as well as loss in ability to use extracellular glutathione and
      activation of methionine use. The thiol drug N-acetylcysteine was also shown to
      be an effective precursor irrespective of the state of differentiation.
      Additionally, myoblasts and myotube cultures were shown to secrete GSH
      continually, but only the differentiated cells responded to stress hormones such
      as glucagon, vasopressin, and phenylephrine, by increased secretion of the
      tripeptide. The data suggest that the skeletal muscle cells may provide an
      important hormonally regulated extra-hepatic source of systemic GSH and also shed
      light on the mechanisms of accelerated turnover of GSH operating during strenuous
      muscle activity and trauma. The data may also provide biochemical rationales for
      the nutritional and/or pharmacological manipulation of GSH with sulfur amino acid
      precursors during the treatment of muscle-specific oxidative stress and atrophy.

PMID- 11821258
TI  - Nonsteroidal anti-inflammatory drugs prevent early diabetic retinopathy via TNF
      alpha suppression.
AB  - Leukocyte adhesion to the diabetic retinal vasculature results in blood-retinal
      barrier breakdown, capillary nonperfusion, and endothelial cell injury and death.
      Intercellular adhesion molecule-1 (ICAM-1) and the leukocyte integrin CD18 are
      required for these processes. Diabetes was induced in Long Evans rats, resulting
      in a two- to threefold increase in retinal leukocyte adhesion. Following one week
      of diabetes, neutrophil CD11a, CD11b, and CD18 expression was increased
      significantly, as were retinal ICAM-1 levels. Animals were treated with aspirin,
      a cyclooxygenase 2 (COX-2) inhibitor (meloxicam), or a soluble tumor necrosis
      factor alpha (TNF-alpha) receptor/Fc construct (TNFR-Fc, etanercept). High-dose
      aspirin, etanercept, and high-dose meloxicam each reduced leukocyte adhesion and
      suppressed blood-retinal barrier breakdown. High-dose aspirin also reduced the
      expression of CD11a, CD11b, and CD18, whereas meloxicam and etanercept did not.
      High-dose aspirin, etanercept, and high-dose meloxicam each reduced retinal ICAM
      1 expression. Aspirin and meloxicam both lowered retinal TNF-alpha levels.
      Notably, aspirin, meloxicam, and etanercept did not change retinal vascular
      endothelial growth factor levels. High-dose aspirin, etanercept and high-dose
      meloxicam, each suppressed the retinal expression of eNOS and the DNA-binding
      capacity of retinal nuclear factor-kappaB. High-dose aspirin also suppressed Erk
      kinase activity, which is involved in CD18 up-regulation. Taken together, these
      data identify COX-2 and TNF-alpha as operative in the early signature pathologies
      of diabetic retinopathy, a newly recognized inflammatory disease.

PMID- 11821259
TI  - Cathepsin D produces antimicrobial peptide parasin I from histone H2A in the skin
      mucosa of fish.
AB  - Parasin I is a potent 19-residue antimicrobial peptide isolated from the skin
      mucus of wounded catfish (Parasilurus asotus). Here we describe the mechanism of
      parasin I production from histone H2A in catfish skin mucosa on epidermal injury.
      Cathepsin D is found to exist in the mucus as an inactive proenzyme (procathepsin
      D), and a metalloprotease, induced on injury, cleaves procathepsin D to generate
      active cathepsin D. This activated form of cathepsin D then cleaves the Ser19
      Arg20 bond of histone H2A to produce parasin I. Immunohistochemical analysis
      reveals that unacetylated histone H2A, a precursor of parasin I, and procathepsin
      D are present in the cytoplasm of epithelial mucous cells and that parasin I is
      produced on the mucosal surface on epidermal injury. Western blot analysis shows
      that parasin I is also present in the skin mucus of other fish species.
      Furthermore, parasin I shows good antimicrobial activity against fish-specific
      bacterial pathogens. Taken together, these results indicate that cathepsin D and
      a metalloprotease participate in the production of parasin I from histone H2A and
      that parasin I contributes to the innate host defense of the fish against
      invading microorganisms.

PMID- 11821260
TI  - Embolization versus myomectomy versus hysterectomy: which is best, when?
AB  - Uterine fibroids are the commonest tumour affecting the female reproductive
      tract. In many instances they are asymptomatic, but in some women there does
      appear to be an association with heavy menstrual blood loss and, possibly,
      subfertility. Classically, treatment has been surgical with hysterectomy the most
      common approach for women who have completed their fertility and myomectomy for
      those who wish to conceive. The surgery can be carried out laparoscopically,
      vaginally and abdominally, although all routes are associated with an appreciable
      rate of morbidity. Myomectomy can also be achieved hysteroscopically.
      Hysterectomy is associated with a high rate of satisfaction and is likely to
      relieve menstrual problems in virtually all women. The success of myomectomy is
      less certain since no randomized trials against expectant management have ever
      been carried out. In addition, myomectomy may lead to adhesion formation within
      the abdominal cavity, which may impair fertility further. Since myomectomy is not
      the ideal answer, other treatments for fibroids are being sought. Medical
      treatment may be useful in specific instances and for the short-term, but does
      not lead to a cure. Consequently, other modalities are being developed, one of
      which is uterine artery embolization. This procedure involves occluding the
      vessels using either foam or coils. The normal myometrium rapidly develops a new
      blood supply from collateral circulations, whereas the fibroids do not. The
      procedure leads to fibroid shrinkage of approximately 30-50% and appears to lead
      to relief of fibroid-associated symptoms, although it is too early to determine
      the effect on fertility. However, it is associated with significant complications
      and requires further evaluation before being accepted as a useful alternative to
      surgical therapy in the management of women with uterine fibroids.

PMID- 11821261
TI  - Human embryo research in France.
AB  - The French law on bioethics, voted upon in July 1994, is going to be revised.
      This is the occasion for France to reconsider its position concerning research on
      human embryos, which is currently prohibited in France, as it is in Germany,
      Switzerland and Austria. However, such research is authorised in other European
      countries such as the UK, Spain, Belgium, Italy and The Netherlands. The
      establishment of human embryonic stem (ES) cells has reopened the debate in
      France because of their potential in human therapy. Indeed, ES cells, derived
      from early embryos (5-6 days old), preserve in vitro a pluripotent character, and
      they could provide an infinite source of different tissues that could be used in
      replacement therapy. This consists of ES cells differentiated in vitro into the
      desired tissues or cell types and grafted into the patient. The use of human ES
      cells in replacement therapy raises the major problem of graft rejection. One of
      the proposed solutions would be to carry out a 'therapeutic cloning' and to
      derive ES cells from the embryos obtained in this way. We do consider that, for
      the moment, the interest of the cloning study lies mainly in the understanding of
      the mechanisms responsible for reprogramming the nuclei. This research can be
      performed first on animal models. France is now thinking to allow human embryo
      research. We present here the French law proposed on human embryo research.
      French government is proposing to allow research exclusively on frozen
      supernumerary embryos, which no longer have any parental or adoption potential.
      Creation of human embryos for research purposes will still be prohibited.
      However, allowance of studies on human cloning in order to realise therapeutic
      cloning is mentioned in the proposal. We think that allowing research in humans
      on therapeutic cloning is premature and contradicts the prohibition of the
      creation of human embryos for research.

PMID- 11821262
TI  - Expression of hypoxia-inducible factors in human endometrium and suppression of
      matrix metalloproteinases under hypoxic conditions do not support a major role
      for hypoxia in regulating tissue breakdown at menstruation.
AB  - BACKGROUND: Classical studies in monkeys suggested that menstruation results from
      vasoconstriction, hypoxia and necrosis. The heterodimeric hypoxia-inducible
      factor (HIF) complex is critical in oxygen homeostasis via increased stability of
      HIF-1alpha/2alpha monomers, and these act as markers of hypoxia. We hypothesized
      that focal hypoxia in perimenstrual endometrium results in locally increased
      matrix metalloproteinases (MMP), leading to tissue destruction. METHODS: HIF
      1alpha, HIF-2alpha and HIF-1beta were immunolocalized in cycling endometrium.
      Endometrial stromal cells were cultured under hypoxic and normoxic conditions and
      MMP measured by zymography and Western blots. RESULTS: HIF-1alpha and HIF-2alpha
      were detected in only some endometrial samples, and not confined to the
      perimenstrual tissue. Where present, they were primarily cytoplasmic, not
      nuclear. HIF-1beta was localized in epithelium, leukocytes and some decidual
      cells. Cultured endometrial stromal cells responded to hypoxia with increased
      cellular HIF-1alpha and secreted vascular endothelial growth factor. ProMMP-1 and
      proMMP-3 production was reduced in response to hypoxia regardless of the
      steroidal milieu (no added steroids, estrogen or estrogen plus progesterone).
      Active MMP-2 and membrane type 1 MMP but not proMMP-2 or proMMP-9 production were
      also inhibited by hypoxia. CONCLUSIONS: These results do not support a role for
      hypoxia in the focally increased production and activation of MMP observed prior
      to and during menstruation.

PMID- 11821263
TI  - Cytotoxic phenotype of intra-epithelial lymphocytes in normal and cryptorchid
      human testicular excurrent ducts.
AB  - BACKGROUND: Most testicular and epididymal lymphocytes express T-cell markers,
      but their cytotoxic potential and activation status have not been reported. In
      this study, distribution of the cytotoxic cells was compared between normal and
      cryptorchid testes stratified into two groups: the first with complete absence of
      germ cells [Sertoli cell-only (SCO)] and the second with arrested spermatogenesis
      (SCA). METHODS: Immunohistochemistry for the T-lymphocyte marker CD3 and
      cytotoxic markers CD8, TIA-1 and granzyme B was performed on paraffin-embedded
      sections. RESULTS: The number of CD8+ and CD3+ intra-epithelial lymphocytes
      (IELs) increased distally throughout the normal epididymis. TIA-1 immunostaining
      revealed that a significant proportion of IELs exhibited cytotoxic potential,
      whereas granzyme B staining disclosed a subpopulation of activated cytotoxic
      lymphocytes (CTLs). TIA-1/CD8 and granzyme B/CD8 double immunostaining revealed
      that the vast majority of TIA-1+ and granzyme B+ cells were CD8+. The proportion
      of activated granzyme B+ lymphocytes increased distally throughout the normal
      epididymis. The number of TIA-1+ and granzyme B+ intra-epithelial and stromal
      lymphocytes was significantly increased in the normal as opposed to the SCO
      cryptorchid epididymis and proximal vas deferens. CONCLUSIONS: These results
      suggest that exposure of the testicular excurrent ducts to spermatozoa or
      immature germ cells triggers the activation and recruitment of CTLs. Cytotoxic
      granule effector mechanisms may contribute to the immunological barrier
      preventing the immune response to spermatozoa in testicular ducts.

PMID- 11821264
TI  - Matrix metalloproteinase-9 and tissue inhibitor of matrix metalloproteinase-1: a
      possible role in the pathogenesis of endometriosis.
AB  - BACKGROUND: Matrix metalloproteinases (MMPs) are a family of endopeptidases which
      play a role in the degradation and turnover of extracellular matrix proteins.
      Their action is regulated by specific tissue inhibitors called tissue inhibitors
      of metalloproteinases (TIMPs). METHODS: We measured the concentrations of total
      and active MMP-9 in peritoneal fluid of infertile women with mild or moderate
      endometriosis (n = 22) and compared them with those in a control group of
      infertile patients (n = 21). RESULTS: We found that the mean (+/-SD) total
      concentrations of MMP-9 in the peritoneal fluid of patients with endometriosis
      was 6.2 +/- 1.8 ng/ml, in comparison with 2.9 +/- 2.6 ng/ml in the control group
      (P = 0.001). Concentrations of active MMP-9 did not differ significantly between
      the groups. The concentrations of TIMP-1, after logarithmic transformation, were
      significantly lower (P = 0.017) in endometriotic peritoneal fluids than in
      peritoneal fluid of control women, 1.02 +/- 0.21 ng/ml and 1.16 +/- 0.18 ng/ml
      respectively. No correlation between stage of disease, steroid hormone
      concentration, MMP-9 (total and active) and TIMP-1 was found. CONCLUSIONS: These
      results suggest that a disturbed equilibrium exists between MMP-9 and TIMP-1 in
      peritoneal fluid of women with endometriosis. This may play an important role in
      the pathogenesis of the disease.

PMID- 11821265
TI  - Co-administration of metformin during rFSH treatment in patients with clomiphene
      citrate-resistant polycystic ovarian syndrome: a prospective randomized trial.
AB  - BACKGROUND: This study aims to evaluate the impact of metformin on ovarian
      response when co-administered during recombinant (r)FSH using the low-dose step
      up protocol in clomiphene citrate-resistant polycystic ovarian syndrome (PCOS)
      patients with normal glucose tolerance. METHODS AND RESULTS: Thirty-two patients
      were randomized to metformin (n = 16) and placebo (n = 16) groups. Hormonal
      assessment, a 75 g oral glucose tolerance test (OGTT) and a frequently sampled
      i.v. glucose tolerance test (FSIGTT) were performed before and after oral
      administration of metformin (850 mg twice daily) or placebo for 6 weeks.
      Recombinant FSH treatment was undertaken, thereafter, in women who did not
      ovulate on metformin (n = 10) or placebo (n = 15). There was no significant
      change in all insulin sensitivity indices in both groups. The only change noted
      was a decline in mean serum free testosterone concentration in the metformin
      group (P = 0.049). One patient on placebo and six patients on metformin ovulated
      spontaneously (P < 0.05). All parameters of ovarian response were comparable
      between the two groups during rFSH treatment. Combining the 6 week placebo or
      metformin-only period with a single rFSH treatment cycle, the overall ovulation
      rates were 75 and 94% in the placebo and metformin groups respectively (P >
      0.05). The respective figures for pregnancy were 6.3 and 31.3% (P > 0.05).
      CONCLUSIONS: Metformin may restore ovulation with no improvement on insulin
      resistance in clomiphene citrate-resistant PCOS patients with normal glucose
      tolerance, but has no significant effect on ovarian response during rFSH
      treatment.

PMID- 11821267
TI  - Evidence of differential control of FSH and LH responses to GnRH by ovarian
      steroids in the luteal phase of the cycle.
AB  - BACKGROUND: It is known that during the follicular phase of the cycle, estradiol
      sensitizes the pituitary to GnRH. The aim of this study was to determine the role
      of ovarian steroids in the control of GnRH-induced gonadotrophin secretion in the
      luteal phase of the cycle. METHODS: Eighteen normally cycling women were studied
      during the week following bilateral ovariectomy plus hysterectomy performed in
      early to mid-luteal phase. Six of the women received no hormonal treatment post
      operatively (group 1, control), six received estradiol through skin patches
      (group 2) and the remaining six received estradiol plus progesterone (group 3).
      In all women the response at 30 min of LH (deltadeltaLH) and FSH (deltadeltaFSH)
      to GnRH (10 microg i.v.) was investigated on a daily basis. RESULTS: In group 1,
      serum FSH, LH and deltadeltaFSH values increased progressively following
      ovariectomy, while in groups 2 and 3 this increase was postponed or abolished. In
      contrast to deltadeltaFSH, deltadeltaLH values showed the same pattern of changes
      in all three groups with a significant decline up to post-operative day 4 and a
      gradual increase thereafter. CONCLUSIONS: These results demonstrate, for the
      first time, that in the early to mid-luteal phase of the cycle, estradiol and
      progesterone participate in the control of GnRH-induced FSH, but not LH,
      secretion. It is possible that in the luteal phase, the response of LH to GnRH is
      partly regulated by gonadotrophin surge attenuating factor.

PMID- 11821266
TI  - Sequential hormonal supplementation with vaginal estradiol and progesterone gel
      corrects the effect of clomiphene on the endometrium in oligo-ovulatory women.
AB  - BACKGROUND: We investigated the possibility of correcting the endometrial
      alterations induced with clomiphene citrate (CC) by vaginal hormonal
      supplementation (HS) with estradiol (E2) and progesterone gel. METHODS: Oligo
      ovulatory women were prospectively randomized into four groups receiving either
      50 mg (groups 1 and 2) or 100 mg (groups 3 and 4) of CC from cycle day 3-8.
      Groups 2 and 4 also received vaginal E2 cream 0.1 mg twice daily from day 8 until
      the LH surge and vaginal progesterone gel, starting 3 days after ovulation. All
      participants had an endometrial biopsy performed 10 +/- 1 days after ovulation.
      RESULTS: All biopsies in the HS groups (2 and 4) showed complete predecidual
      changes, and were 'in-phase' with findings normally made 10 days post-ovulation
      (+/- 2 days of clinical dating). However, without HS (groups 1 and 3), only 4/6
      and 3/6 biopsies showed predecidual changes in women receiving 50 and 100 mg of
      CC. CONCLUSION: The addition of vaginal E2 and progesterone to CC ovulation
      induction regimens normalizes the alterations in endometrial morphology. Hormonal
      treatment combining vaginal E2 and progesterone may improve endometrial
      receptivity in CC cycles and ultimately yield higher pregnancy rates.

PMID- 11821268
TI  - Delivery rates following IVF treatment, using two recombinant FSH preparations
      for ovarian stimulation.
AB  - BACKGROUND: A prospective, semi-randomized, open, clinical study was conducted to
      compare ovarian response, pregnancy outcome and delivery rates using two
      recombinant FSH preparations (Gonal-F and Puregon) for IVF. METHODS: We analysed
      stimulation parameters and outcome data in 812 initiated treatment cycles where
      292 women used Gonal-F and 200 used Puregon. Embryo transfer was carried out in
      676 cycles. In the two preparation groups we also compared 170 women previously
      treated with FSH for IVF with 266 previously untreated. RESULTS: The pregnancy
      rate with Gonal-F was 26% and with Puregon 28%. Delivery rates were identical,
      22%. Clinical pregnancy and delivery rates per cycle with embryo transfer in
      earlier untreated women were 29.0 and 24.0%, whereas in previously treated women
      they were 23.5 and 18.8% respectively. After repeated cycles, delivery
      frequencies consecutively decreased, independent of the FSH preparation used.
      CONCLUSION: Gonal-F and Puregon seem to be equally potent in achieving follicular
      development and equally effective, in terms of delivery rates, for use in an IVF
      programme. Repeated cycles resulted in equally large consecutive decreases in
      delivery rates, regardless of preparation choice, but were considered worthwhile
      for up to three stimulation cycles in selected patients.

PMID- 11821269
TI  - The significance of coasting duration during ovarian stimulation for conception
      in assisted fertilization cycles.
AB  - BACKGROUND: Withholding gonadotrophin administration and postponing HCG
      injection, termed coasting, has been suggested as a treatment modality in cases
      of impending ovarian hyperstimulation syndrome (OHSS). It presents an opportunity
      to reduce the risk of OHSS and salvage the treatment, without apparent compromise
      to outcome. However, the duration of the coasting period, which would maintain
      the advantage without reducing conception rate, has not been fully established.
      In this retrospective study, we attempted to define the optimal interval of
      coasting in patients at risk of developing OHSS. METHODS: Patients were grouped
      according to the number of days elapsed between cessation of gonadotrophins and
      administration of HCG. Overall, out of 207 patients (mean age 30.76 +/- 0.33
      years) coasting lasted 1 day in 39 cycles (18.8%), 2 days in 61 cycles (29.4%), 3
      days in 49 cycles (23.6%) and > or = 4 days in the remaining 58 cycles (28.5%).
      RESULTS: There was no difference between the groups in patients' age, serum
      estradiol concentrations at the time of HCG administration, oocyte maturity,
      fertilization and embryo cleavage rates. However, patients in whom coasting
      lasted > or = 4 days had significantly reduced implantation (10.5%) and pregnancy
      (26.7%) rates compared with patients with a shorter coasting interval (ranges
      18.4-27.9 and 41-55.7% respectively; P < 0.05). CONCLUSION: Coasting for >3 days
      appears to reduce implantation and pregnancy rates while in-vitro oocyte and
      embryo quality do not appear to be affected. We suggest that in patients who need
      coasting for >3 days, cryopreservation of embryos should be considered.

PMID- 11821271
TI  - Preferential location of sex chromosomes, their aneuploidy in human sperm, and
      their role in determining sex chromosome aneuploidy in embryos after ICSI.
AB  - BACKGROUND: In babies born after ICSI procedures, an increase of de-novo sex
      chromosome abnormalities has been observed. Several hypotheses have been proposed
      to explain these findings: an increased rate of sex chromosome aneuploidy in
      sperm of oligozoospermic men, or a preferential location of the sex chromosomes
      in the sub-acrosomal region of the sperm nucleus which leads to a reduced DNA
      decondensation of this region. In order to investigate which theory may be more
      reliable, we studied the localization of sex chromosomes and their aneuploidy
      rate in sperm in men undergoing ICSI. METHODS: Using fluorescent in-situ
      hybridization we studied sex chromosome localization and the aneuploidy rate for
      sex chromosomes and chromosome 18 in 20 oligospermic men undergoing ICSI and in
      10 controls. RESULTS: In 40.94 and 52.92% of cases, the X and Y chromosomes
      respectively were localized in the sub-acrosomal region of the sperm nucleus
      compared with only 14.29% of cases of chromosome 18 (P < 0.001). An increase of
      sex chromosome aneuploidy in sperm of oligospermic men was observed; 2.91 versus
      0.69% of controls (P < 0.001). CONCLUSIONS: Sex chromosomes are localized
      preferentially in the sub-acrosomal region of sperm and sex chromosome aneuploidy
      rate in the sperm of oligozoospermic men is higher than in controls.

PMID- 11821270
TI  - Polycystic ovarian syndrome and thrombophilia.
AB  - BACKGROUND: Polycystic ovarian syndrome (PCOS) is associated with insulin-induced
      plasminogen activator inhibitor-1 (PAI-1) elevations. Since thrombophilic states
      correlate with high miscariage rates, as does PCOS, this study aimed at looking
      for thrombophilic predisposition in PCOS women compared with non-PCOS controls.
      METHODS: The prevalence of antithrombin III, protein S and protein C
      deficiencies, as well as factor V Leiden, prothrombin G20210A factor and
      methylene tetrahydrofolate reductase (MTHFR) mutations, was compared between two
      different groups of women, one with PCOS (n = 30) and one without PCOS (n = 45).
      RESULTS: Median proportions of activated protein C, S and antithrombin III as
      well as the activated protein C ratios were within normal ranges in both samples.
      There was no evidence that the genetic analysis for factor V Leiden or
      prothrombin factor differed between the two samples. The odds ratio (OR) of
      bearing a mutation on the MTHFR gene was 1.2-fold higher [95% confidence interval
      (CI) 0.470-3.065] in women with PCOS than in women without (P = 0.83). Although
      this difference is not statistically significant, it might indicate a slightly
      higher prevalence of heterozygous genotypes in women with PCOS (OR = 1.197, 95%
      CI 0.473-3.034). CONCLUSIONS: Molecular risk factors of hereditary thrombophilia
      do not show increased prevalence in women with PCOS in comparison with women in
      the general population. The existence of a possible trend towards higher
      prevalence of MTHFR mutation in women with PCOS needs further study, particularly
      regarding homocysteine levels.

PMID- 11821272
TI  - Sperm analysis by FISH in a case of t(17; 22) (q11; q12) balanced translocation:
      case report.
AB  - Individual sperm from men with balanced translocations have different chromosomal
      contents. Thus, an estimation of the overall sperm chromosomal imbalance of such
      patients could help to give the couple an adapted genetic counselling. We report
      here the study of a balanced translocation carrier, t(17;22) (q11;q12) whose
      reproductive history reported four miscarriages. Moreover, he had an abnormal
      semen analysis with oligoteratozoospermia. The meiotic segregation pattern was
      examined in 700 sperm, using fluorescence in-situ hybridization (FISH). Nineteen
      percent of the sperm had balanced translocations or were normal. All other sperm
      were unbalanced (81%) and their distribution was observed as follows: the
      frequencies of adjacent 1, adjacent 2 and 3:1 segregations were 12.9, 5.8 and
      46.8% respectively. Among the segregations scored, 13.7% were related to second
      meiotic division abnormalities. Less than 2% of the total sperm scored were not
      explained. The 3:1 segregation was present at a very high rate, which is very
      unusual. In cases of balanced translocations, we believe that no general features
      can be drawn. Thus, the FISH technique may be very helpful for genetic
      counselling, which remains an important step and must be done with care.

PMID- 11821273
TI  - Pharmacokinetics of different routes of administration of misoprostol.
AB  - BACKGROUND: The pharmacokinetic parameters of four different routes of
      administration of a single dose of 400 microg of misoprostol were studied.
      METHODS: A total of 40 women undergoing termination of pregnancy by suction
      evacuation was randomized by computer model to receive 400 microg of misoprostol
      by one of four routes: (i) sublingual (ii) oral (iii) vaginal and (iv) vaginal
      with addition of water. Venous blood samples were taken at 0, 1, 2, 5, 10, 20,
      30, 45, 60, 120, 240 and 360 min after the administration of misoprostol.
      Misoprostol acid (MPA) was determined in serum samples using gas
      chromatography/tandem mass spectrometry. RESULTS: Sublingual misoprostol achieved
      the highest serum peak concentration (Cmax) (574.8 +/- 250.7 pg/ml) of MPA and
      this was significantly higher than those in the other groups [Oral: 287.6 +/-
      144.3 pg/ml (P < 0.01), vaginal: 125.2 +/- 53.8 pg/ml (P < 0.001) and vaginal
      with water: 162.8 +/- 57.1 pg/ml (P < 0.001)]. The time to peak concentration
      (Tmax) was similar in both the sublingual (26.0 +/- 11.5 min) and oral groups
      (27.5 +/- 14.8 min) and was significantly shorter than those in both vaginal
      groups. The area under the MPA concentration versus time curve up to 360 min in
      the sublingual group (743.7 +/- 291.2 pg.h/ml) was significantly greater than
      those in oral (402.8 +/- 151.6 pg.h/ml, P < 0.05) and vaginal (433.7 +/- 182.6
      pg.h/ml, P < 0.05) groups, but no significant difference was found between
      sublingual and vaginal administration if water (649.3 +/- 333.8 pg.h/ml) was
      added. CONCLUSION: The new sublingual route of administration of misoprostol
      demonstrated a great potential to be developed into a method of medical abortion.

PMID- 11821274
TI  - Bacterial colonization of the uterine cervix and success rate in assisted
      reproduction: results of a prospective survey.
AB  - BACKGROUND: Overgrowth of bacteria in the birth canal is associated with an
      increased risk of late miscarriage, preterm labour, post-partum endometritis and
      low birthweight. Conception rates in assisted reproduction treatments (ART)
      remain frustratingly low. We examined whether the nature of bacterial flora,
      found in the uterine cervical canal at embryo transfer, is associated with the
      rate of conception in ART. METHODS: We sampled for bacteriological culture the
      cervical canal of 204 patients who underwent embryo transfer. Of these, 139 (68%)
      were of fresh embryos, following recent vaginal oocyte retrieval and prophylactic
      antibiotic therapy, and 65 (32%) of frozen-thawed embryos, without any vaginal
      intervention in the preceding days. Bacteriological work-up included
      identification, colony count and antibiotic susceptibility profile. Conception
      was correlated with bacterial type and colony count. RESULTS: In 75 patients
      (36.8%) sterile cervical cultures or lactobacillus were recorded. Of these 75
      patients, 23 (30.7%) conceived, whereas among the 129 in whom any pathogenic
      micro-organism was recovered only 21 (16.3%) conceived (P = 0.002). No difference
      in colonization was found between women who underwent frozen-thawed versus fresh
      embryo transfer (57 and 67% respectively). Any Gram-negative colonization was
      associated with no conception. All Gram-positive, and 90% of the Gram-negative
      bacteria, were sensitive to augmentin. CONCLUSIONS: Failure to conceive in ART is
      significantly associated with bacterial colonization of the uterine cervix.

PMID- 11821275
TI  - The influence of the depth of embryo replacement into the uterine cavity on
      implantation rates after IVF: a controlled, ultrasound-guided study.
AB  - BACKGROUND: Traditionally, embryo transfer after IVF has been performed blindly
      and placing the embryos approximately 1 cm below the fundal endometrial surface.
      However, it has been suggested that transferring embryos rather lower in the
      uterine cavity or high in the uterus may improve implantation rates.
      Nevertheless, there has not yet been a controlled trial to prove this theory.
      This prospective randomized study investigates the influence of the depth of
      embryo replacement on the implantation rate after embryo transfer carried out
      under transabdominal ultrasound guidance. METHODS: A total of 180 consecutive
      patients undergoing ultrasound-guided embryo transfer were randomized to three
      study groups according to the distance between the tip of the catheter and the
      uterine fundus at the moment of the embryo deposition in the lumen of the
      endometrial cavity: group 1: 10 +/- 1.5 mm; group 2: 15 +/- 1.5 mm; group 3: 20
      +/- 1.5 mm. RESULTS: There was equal distribution between all three study groups
      regarding the main demographic and baseline characteristics of the patients,
      ovarian response, oocyte retrieval and IVF outcome, as well as the
      characteristics of embryo transfer and luteal phase support. The position of the
      catheter tip in relation to the fundal endometrial surface in groups 1 (10.2 +/-
      0.9 mm), 2 (14.6 +/- 0.7 mm) and 3 (19.3 +/- 0.8 mm) was significantly different.
      Implantation rate was significantly higher (P < 0.05) in groups 2 (31.3%) and 3
      (33.3%) compared with group 1 (20.6%). CONCLUSIONS: The depth of the embryo
      replacement into the uterine cavity may influence implantation rates, and thus it
      should be considered as an additional procedure among factors recently proposed
      as associated with successful embryo transfer after IVF.

PMID- 11821276
TI  - Transmyometrial embryo transfer and junctional zone contractions.
AB  - BACKGROUND: Embryo transfer is a crucial step in IVF-embryo transfer cycles.
      Several studies have explored transmyometrial embryo transfer, but although this
      procedure has several favourable characteristics, its role in assisted
      reproduction has not yet been established. Junctional zone (JZ) contractions
      during embryo transfer are associated with a negative outcome and factors which
      increase JZ contractions should be avoided. METHODS: In this study, we have
      investigated the effect of transmyometrial embryo transfer on JZ contractions.
      Ten patients with a previously difficult embryo transfer, or a difficult mock
      embryo transfer, underwent transmyometrial embryo transfer. Before and after this
      procedure a transvaginal ultrasound scan was performed and this was recorded on
      videotape for 5 min. The recordings were digitized and then analysed for JZ
      contractions. RESULTS: Transmyometrial embryo transfer causes a significant
      increase in JZ contractions. CONCLUSION: The increase in JZ contractions after
      transmyometrial embryo transfer forms a theoretical objection to this procedure.
      However, its alternative, a difficult transcervical embryo transfer, is also
      associated with an increase in JZ contractions. We therefore suggest a large
      prospective study to investigate the most effective method of embryo transfer in
      cases where a difficult transcervical embryo transfer is anticipated due to
      cervical factors.

PMID- 11821277
TI  - Fluid accumulation within the uterine cavity reduces pregnancy rates in women
      undergoing IVF.
AB  - BACKGROUND: The occurrence of fluid accumulation within the uterine cavity was
      examined in women undergoing IVF to investigate its correlation with tubal
      disease and impact on the pregnancy outcome. METHODS: A registry of ultrasound
      procedures spanning 5 years was retrospectively studied. RESULTS: Thirty five out
      of 746 (4.7%) IVF cycles were identified as having uterine fluid accumulation,
      and 15 (2.0%) persisted until the day of embryo transfer. Two of the 20 cycles of
      women with transient fluid accumulation were pregnant, and none of those with
      fluid retention on the day of embryo transfer conceived. The pregnancy rate was
      only 5.7% (2/35) in women with uterine fluid accumulation detected during IVF
      cycles. In contrast, the pregnancy rate was 27.1% (193/711) among women in whose
      cycles no fluid accumulation was detected (P = 0.0048). Uterine fluid
      accumulation during IVF cycles was found in 8% (18/225) of women documented with
      tubal factor compared with 3.3% (17/521) with non-tubal factor (P = 0.005).
      CONCLUSIONS: Fluid accumulation within the uterine cavity during the IVF transfer
      treatment could be observed in patients with both tubal and non-tubal factors;
      however, it mainly occurred in women with tubal infertility. Although it is not a
      common complication of IVF cycles, excessive uterine fluid is detrimental to
      embryo implantation.

PMID- 11821279
TI  - Outcome of conventional IVF and ICSI on sibling oocytes in mild male factor
      infertility.
AB  - BACKGROUND: Decisions concerning the treatment choice for assisted reproduction
      (IVF or ICSI) are usually made after the evaluation of male fertility factors, or
      after taking into account the results of previous IVF attempts. There are no
      widely accepted criteria, so decisions for couples with male subfertility are
      often empirical and may lead to complete fertilization failure after IVF, or to
      the unnecessary use of ICSI. METHODS: A study was conducted in which half the
      oocytes from each of 58 couples with moderate oligo +/- astheno +/-
      teratozoospermia were inseminated (conventional IVF) and the other half
      microinjected (ICSI). The technique used for subsequent cycles depended on the
      results of the first cycle. RESULTS: Nineteen of the 58 IVF/ICSI attempts
      resulted in fertilization after ICSI only (32.8%) and 39 in fertilization after
      IVF and ICSI (67.2%). For patients with oocyte fertilization only after ICSI,
      61.5% of the oocytes microinjected were fertilized. A mean of 2.2 embryos per
      patient were transferred, leading to eight clinical pregnancies (42.1%). The
      implantation rate was 21.4%. All subsequent cycles were carried out with ICSI.
      Couples with oocyte fertilization after both IVF and ICSI had slightly better
      semen characteristics than those with oocyte fertilization only after ICSI, but
      this difference was not significant. Overall, no statistically significant
      difference was observed between IVF and ICSI in sibling oocytes for any of the
      variables studied: fertilization rate, embryo morphology and rates of
      development, pregnancy and implantation. Although only small numbers of oocytes
      or embryos were available for each couple, six couples had lower fertilization
      rates after IVF and eight had lower embryo quality after IVF. Eight patients had
      lower sperm quality in the second cycle, and only seven couples underwent
      subsequent IVF cycles. CONCLUSIONS: This strategy enabled us to avoid 32.8% of
      complete fertilization failures after IVF, but not to decrease significantly the
      number of ICSI attempts in subsequent cycles. However, the uncertainties
      concerning the safety of ICSI suggest that ICSI should be used cautiously and
      judiciously.

PMID- 11821278
TI  - Progesterone supplementation during early gestations after IVF or ICSI has no
      effect on the delivery rates: a randomized controlled trial.
AB  - BACKGROUND: The aim was to study whether prolongation of luteal support during
      early pregnancy influences the delivery rate after IVF. METHODS: Dual centre
      study including 303 women who achieved pregnancy after IVF or ICSI was used. All
      were treated with the long protocol using GnRH agonists and given luteal support
      with 200 mg vaginal progesterone three times daily during 14 days from the day of
      transfer until the day of a positive HCG test. The study group (n = 150) withdrew
      vaginal progesterone from the day of positive HCG. The control group (n = 153)
      continued administration of vaginal progesterone during the next 3 weeks of
      pregnancy. RESULTS: The number of miscarriages prior to and after week 7 of
      gestation was seven (4.6%) and 15 (10.0%) in the study group and five (3.3%) and
      13 (8.5%) in the control group respectively. The number of deliveries was 118
      (78.7 %) in the study group and 126 (82.4 %) in the control group. The
      differences were not significant. CONCLUSIONS: Prolongation of progesterone
      supplementation in early pregnancy has no influence on the miscarriage rate, and
      thus no effect on the delivery rate. Progesterone supplementation can safely be
      withdrawn at the time of a positive HCG test.

PMID- 11821280
TI  - Long term safety of fluoroscopically guided selective salpingography and tubal
      catheterization.
AB  - BACKGROUND: The irradiation of the ovaries of reproductive age women during
      fluoroscopically guided selective salpingography and tubal catheterization has
      raised concern about the safety of the procedure. In addition to the risk of
      cancer induction, which exists with the irradiation of all tissues, with the
      gonads, the induction of hereditary disorders is possible. The objective of this
      study was to estimate these risks and present them in a clinically meaningful
      way. METHODS: Retrospective analysis was undertaken of 366 consecutive cases of
      selective salpingography and tubal catheterization performed at the Birmingham
      Women's Hospital, UK. The radiation doses of different types of procedure were
      compared with the background annual radiation dose. The risks of cancer and
      genetic disorders induction were calculated using conversion coefficients
      published by the International Commission on Radiological Protection. RESULTS:
      The radiation dose women were exposed to during selective salpingography and
      tubal catheterization under fluoroscopic guidance was a fraction of the
      background annual radiation dose. The excess lifetime risks of cancer and
      hereditary disorders were in the order of four to 13 and two to six per million
      procedures respectively. CONCLUSIONS: The long term risks of selective
      salpingography and tubal catheterization under fluoroscopic guidance are low.

PMID- 11821281
TI  - Successful pregnancy resulting from in-vitro matured oocytes retrieved at
      laparoscopic surgery in a patient with polycystic ovary syndrome: case report.
AB  - Combined laparoscopic retrieval of immature oocytes and ovarian electrocautery
      represents a new management in patients with polycystic ovary syndrome (PCOS),
      one of the most prevalent endocrinopathies associated with anovulatory
      infertility. A 31-year-old para II presented with anovulatory, clomiphene
      resistant PCOS, and a 6 year history of infertility. Conventional IVF treatment
      was abandoned in 1999 when she developed severe ovarian hyperstimulation syndrome
      (OHSS) following gonadotrophin stimulation. Sixteen oocytes were aspirated from
      both ovaries and collected in culture tubes containing a maturation medium. A
      total of three 2-cell embryos were transferred 48 h after ICSI. Two weeks after
      embryo transfer the urinary pregnancy test was positive and after another 2 weeks
      an ongoing singleton pregnancy with a fetal heartbeat was confirmed at
      transvaginal ultrasound examination. The combination of laparoscopy, in-vitro
      maturation and ICSI may open up new therapeutic strategies, even in patients
      without PCOS and regular menstrual cycles, undergoing laparoscopy for other
      causes of infertility such as tubal factors and endometriosis.

PMID- 11821282
TI  - Response of midpiece vesicles on human sperm to osmotic stress.
AB  - BACKGROUND: We investigated the osmotic response of midpiece vesicles (MPV) on
      human sperm. METHODS: Light microscopy, transmission X-ray microscopy and
      computer-aided semen analysis was used to investigate sperm in normozoospermic
      semen from healthy donors, separated from semen and suspended in hyper- or hypo
      osmotic solutions. RESULTS: The mean incidence of MPV-bearing sperm in semen was
      31% (range 8-71; n = 47). MPV were morphologically different from cytoplasmic
      droplets. The incidence of MPV-bearing sperm in separated populations increased
      reversibly after washing in Sperm Preparation Medium but not after washing in
      seminal plasma. There was an inverse relationship between medium osmolality and
      both MPV-bearing sperm incidence and MPV diameter. However, initial osmolality in
      semen from different donors did not correlate with incidence of MPV-bearing
      sperm. Furthermore, a direct relationship was observed in semen as osmolality
      increased with time. No correlation existed between progressive motility and
      semen osmolality. Progressive motility and the amplitude of lateral head
      displacement were significantly reduced in sperm with an MPV (three out of four
      semen samples, 26-32 sperm). The incidence of MPV-bearing sperm in those that had
      penetrated cervical mucus (75, 46, and 40%) was increased compared with the
      adjacent semen (24, 35, and 24%). CONCLUSIONS: MPV are ubiquitous and distinct
      from cytoplasmic droplets. They respond to osmolality changes of the surrounding
      medium. The presence of an MPV can reduce motility but not survival in cervical
      mucus. Therefore, they should not be considered detrimental to sperm function.

PMID- 11821283
TI  - Long-term cultures of testicular biopsies from boys with cryptorchidism: effect
      of FSH and LH on the number of germ cells.
AB  - BACKGROUND: A long-term culture system of testicular biopsies from boys with
      undescended testes was established to evaluate the effect of gonadotrophins on
      germ cell survival and growth. METHODS: Biopsies from 25 boys with
      cryptorchidism, aged 1.1-9.9 years, were obtained at the time of surgery. Each
      biopsy was subdivided into fragments and cultured for 1 or 3 weeks in a testis
      culture medium without gonadotrophins or supplemented with FSH (50 IU/l) or LH (5
      IU/l), or a combination of FSH (50 IU/l) plus LH (5 IU/l). The survival of the
      germ cells was evaluated by calculating the ratio of spermatogonia and gonocytes
      per cross-sectioned testicular tubule, the S/T ratio. RESULTS: All cultured
      fragments maintained their overall morphology. A significantly reduced S/T ratio
      was observed in the fragments cultured in the presence of LH (P = 0.006),
      independently of the culture period. The mean tubular diameter in fragments
      cultured for 1 week with hormones was significantly larger than that of the
      controls (P < 0.0002). All cultured fragments had a larger tubular diameter than
      the uncultured fragments (P = 0.0002). CONCLUSIONS: This culture system supports
      survival of spermatogonia for at least 3 weeks. LH either alone or in combination
      with FSH results in a significantly reduced S/T ratio.

PMID- 11821284
TI  - The use of ICSI with fresh and cryopreserved electroejaculates from psychogenic
      anejaculatory men.
AB  - BACKGROUND: Electroejaculation has become an accepted form of semen procurement
      in men suffering from anejaculation. However, sperm in these ejaculates often
      exhibit low motility. In such cases, ICSI is offered to improve the possibility
      of successful pregnancy. Here we evaluate the fertilizing potential, using ICSI,
      of fresh and cryopreserved sperm obtained by transrectal electroejaculation from
      patients with psychogenic anejaculation. METHODS: A total of 25 men suffering
      from psychogenic anejaculation underwent 37 sessions of electroejaculation in
      combination with ICSI. In 17 patients fresh sperm (29 cycles, group I) was used,
      and in the other eight patients cryopreserved sperm (10 cycles, group II) was
      used. RESULTS: A total of 155 oocytes were injected with fresh sperm with a
      fertilization rate of 55% (85/155). The pregnancy rate was 10% (3/29) per cycle.
      A total of 94 oocytes were injected with frozen-thawed sperm with a fertilization
      rate of 50% (47/94). The pregnancy rate was 40% (4/10) per cycle. CONCLUSIONS:
      The fertilization and pregnancy rates with cryopreserved sperm from
      electroejaculation are at least as good as those of freshly obtained sperm.
      Therefore, when motile sperm is found in the thawed ejaculate, additional
      electroejaculation can be avoided.

PMID- 11821285
TI  - Domains of high-polarized and low-polarized mitochondria may occur in mouse and
      human oocytes and early embryos.
AB  - BACKGROUND: The magnitude of the inner mitochondrial membrane potential
      (deltapsim) appears to influence the level of certain mitochondrial activities
      including regulation of ionic fluxes and ATP liberation, activities that are
      often compartmentalized or location dependent in cells. Recent evidence suggests
      that within cells, mitochondria can be heterogeneous with respect to deltapsim,
      and that high-polarized mitochondria (high deltapsim) may occur in the
      subplasmalemmal cytoplasm where intercellular contact is absent. Here, we
      investigated whether deltapsim in oocytes and preimplantation embryos was
      heterogeneous and cell contact-associated. METHODS: Mouse and human oocytes and
      preimplantation stage embryos stained with mitochondria-specific probes rhodamine
      123, MitoTracker Orange, and the deltapsim-sensitive probe JC-1, (5,5',6,6'
      tetrachloro-1,1,3,3'-tetraethylbenzimidazoylcarbocyanine iodide), were examined
      by epifluorescence, scanning laser confocal, and transmission electron
      microscopy. The possibility that intercellular contact and deltapsim are
      associated was examined for oocytes, where transzonal coronal cell contacts were
      terminated naturally or experimentally, and for intact, disaggregated, and
      reconstructed cleavage stage mouse embryos. RESULTS: For both oocytes and
      embryos, clusters of apparently high-polarized mitochondria occur in the
      pericortical cytoplasm in regions free from intercellular contact. CONCLUSIONS:
      The findings suggest that mitochondria in oocytes and preimplantation embryos may
      be heterogeneous with respect to deltapsim. We propose that high-polarized
      pericortical mitochondria may have a role in the acquisition of oocyte competence
      and the regulation of early developmental processes that may be associated with
      elevated metabolism or intracellular signalling through calcium-induced calcium
      release pathways.

PMID- 11821286
TI  - Time from insemination to first cleavage predicts developmental competence of
      human preimplantation embryos in vitro.
AB  - BACKGROUND: The absence of reliable markers for the identification of viable
      embryos for transfer at the early cleavage stage is likely to contribute to the
      generally low implantation rates and high incidence of multiple gestation in IVF
      treatment. In this study, we investigate the relationship between timing of first
      cleavage and the incidence of blastocyst formation in vitro. METHODS: Couples (n
      = 70) with at least one embryo remaining after transfer were included in the
      analyses. All embryos (n = 579) were examined for early cleavage at 25 h after
      insemination. Following embryo transfer, the remaining embryos (n = 426) were
      cultured until day 7 of development, and assessed for blastocyst formation.
      RESULTS: Eighty-five embryos (14.7%) cleaved to the 2-cell stage within 25 h of
      insemination; 26 of these were selected for transfer on day 2. Of the 59 embryos
      remaining in culture, 19 (32.2%) developed to the blastocyst stage; this was a
      significantly higher number than was observed in embryos (61/367; 16.6%) that
      failed to cleave within 25 h of insemination (P < 0.01). Within these two groups
      of embryos the proportion of hatched blastocysts was 11/59 (18.6%) and 26/367
      (7.1%) respectively (P < 0.005). CONCLUSIONS: These findings indicate that early
      cleavage is indicative of increased developmental potential in human embryos and
      may be useful as an additional criterion in the selection of embryos for
      transfer.

PMID- 11821287
TI  - Chromosomal mosaicism throughout human preimplantation development in vitro:
      incidence, type, and relevance to embryo outcome.
AB  - BACKGROUND: A large percentage of in-vitro generated cleavage stage human embryos
      are chromosomally mosaic, consisting of both normal (diploid) and abnormal (non
      diploid) cells. The present study characterized mosaicism at each stage of
      cleavage division and examined its effect on preimplantation development in
      vitro. METHODS: A total of 216 normally fertilized (two-pronucleate) embryos
      which were not selected for transfer to the patients were analysed for
      chromosomal abnormalities using multi-colour fluorescence in-situ hybridization
      DNA probes specific for three to five of nine different chromosomes (X, Y, 2, 7,
      13, 16, 18, 21, 22). RESULTS: Overall, 48.1% of embryos were mosaic. The
      frequency of mosaic embryos increased from 15.2 to 49.4 to 58.1%, from the 2-4
      cell to 5-8-cell to morula stages respectively, and the types of non-diploid
      cells detected were mostly aneuploid or chaotic. The incidence of mosaicism at
      the blastocyst stage was 90.9%; however, most of the mosaicism comprised diploid
      and polyploid cells. Arrested mosaic embryos had a higher incidence of chaotic
      abnormalities, and higher proportions of abnormal cells compared with the non
      arrested group. CONCLUSIONS: Post-zygotic errors leading to mosaicism may occur,
      and persist throughout preimplantation development in vitro. Our results suggest
      that mosaicism involving multiple chromosomal imbalances and/or imbalances
      affecting a high proportion of cells in an embryo appear to impair development to
      the blastocyst stage.

PMID- 11821288
TI  - A cytogenetic study of in-vitro matured murine oocytes after ICSI by human sperm.
AB  - BACKGROUND: The purpose of this study was to investigate the chromosomal
      complement and developmental potential of in-vitro matured murine oocytes
      following ICSI by human sperm. METHODS: Heterologous ICSI fertilization between
      mouse oocytes and human sperm was employed in order to overcome the reduced
      fertilization rates observed after conventional IVF due to zona hardening during
      in-vitro maturation, and to assess separately maternal and paternal chromosome
      complements. Cytogenetic analyses were performed in four types of oocytes: (i) in
      vitro matured metaphase II (MII) oocytes; (ii) in-vivo matured MII oocytes; (iii)
      in-vitro matured oocytes after ICSI; (iv) in-vivo matured oocytes after ICSI.
      RESULTS: Activation rates after ICSI of in-vitro matured oocytes was lower than
      that of in-vivo matured oocytes (69.9 versus 97.2%, P < 0.01), and premature
      chromosomal condensation was only observed in in-vitro matured oocytes. However,
      there were no significant differences in developmental rates after successful
      activation between in-vivo and in-vitro matured ICSI oocytes (69.7 versus 76.6%).
      The incidences of aneuploidy and structural aberrations were similar between the
      ICSI embryos and non-ICSI (MII) oocytes. Furthermore, the frequency of
      chromosomal aberrations was not associated with in-vitro or in-vivo maturation.
      Similar analyses of paternal chromosomes indicated that there were no significant
      differences in the incidence of chromosomal aberrations between the embryos
      derived from in-vitro and in-vivo matured oocytes. CONCLUSIONS: These results
      suggest that in-vitro matured oocytes following ICSI do not lead to an increase
      in the frequency of aneuploidy and structural aberrations when human sperm are
      injected into mouse oocytes.

PMID- 11821290
TI  - Histopathological analysis of laparoscopically treated ovarian endometriotic
      cysts with special reference to loss of follicles.
AB  - BACKGROUND: The best operative procedure for the laparoscopic treatment of
      ovarian endometriotic cysts has yet to be defined. The purpose of this study was
      to evaluate the association between laparoscopic cystectomy and loss of
      follicles. METHODS: Videotape records of the laparoscopic removal of 73 ovarian
      cysts, histologically confirmed in the focal endometrial epithelial lining, were
      retrospectively reviewed. They were divided into two groups: group 1 (61 cysts)
      in which the capsule was easily stripped from the underlying ovarian tissue and
      group 2 (12 cysts) in which the capsule could hardly be stripped from the
      underlying ovarian tissue. Main outcome measures included attached capsular
      structures and the number of attached follicles. RESULTS: Microscopically in all
      group 1 cysts, normal ovarian stroma was attached to the resected side of the
      capsule. In addition, 30/61 (49.1%) of group 1 cysts were attached to the corpus
      albicans. The primordial follicle was found within the capsule of 42/61 (68.9%)
      group 1 cysts. The number of primordial follicles ranged from 1-25 (mean 6.6). In
      group 2 cysts, no primordial follicles were found. CONCLUSION: The relative ease
      of removal of the capsules is probably associated with loss of follicles and
      damage to the ovarian stroma.

PMID- 11821289
TI  - Prediction of endometriosis with serum and peritoneal fluid markers: a
      prospective controlled trial.
AB  - BACKGROUND: The objective of this prospective controlled trial was to investigate
      the ability of a group of serum and peritoneal fluid (PF) markers to predict, non
      surgically, endometriosis. METHODS AND RESULTS: Serum and PF samples were
      obtained from 130 women while undergoing laparoscopy for pain, infertility, tubal
      ligation or sterilization reversal. Concentrations of six cytokines [interleukin
      (IL)-1beta, IL-6, IL-8, IL-12, IL-13 and tumour necrosis factor (TNF)-alpha] were
      measured in serum and PF, and reactive oxygen species (ROS) in PF, and levels
      were compared among women who were allocated to groups according to their post
      surgical diagnosis. Fifty-six patients were diagnosed with endometriosis, eight
      with idiopathic infertility, 27 underwent tubal ligation or reanastomosis
      (control group) and 39 were excluded due to bloody PF. Only serum IL-6 and PF TNF
      alpha could be used to discriminate between patients with and without
      endometriosis with a high degree of sensitivity and specificity (P < 0.001). A
      threshold of 15 pg/ml PF TNF-alpha provided 100% sensitivity and 89% specificity
      (positive likelihood ratio of 9.1 and negative likelihood ratio of 0). A
      threshold of 2 pg/ml for serum IL-6 provided a sensitivity of 90% and specificity
      of 67% (positive likelihood ratio of 2.7 and negative likelihood ratio of 0.14).
      CONCLUSIONS: By measuring serum IL-6 and PF TNF-alpha, it was possible to
      discriminate between patients with endometriosis and those without. Before these
      markers can be used as a non-surgical diagnostic tool, these data should be
      verified in a larger study.

PMID- 11821291
TI  - Combination antiretroviral therapy in 100 HIV-1-infected pregnant women.
AB  - BACKGROUND: In recent years, combination antiretroviral therapy has substantially
      improved the prognosis of human immunodeficiency virus type-1 (HIV-1) infection.
      However, at present, information regarding the effects of these regimens during
      pregnancy is limited. METHODS: Side-effects, vertical transmission rate and
      neonatal outcome associated with different combination therapies were evaluated
      retrospectively in a consecutive series of 100 women who attended the II
      Department of Obstetrics and Gynecology for the management of HIV-1 infection in
      pregnancy. RESULTS: Antiretroviral treatment was initiated at a median of 16
      weeks gestation with a range from pre-pregnancy until 31 weeks gestation.
      Twentythree women continued their pre-pregnancy therapy during the first
      trimester of gestation. Protease inhibitors were incorporated in 23 of the final
      therapeutic regimens. Twentyfive women did not receive zidovudine. Most women
      (97) delivered by Caesarean section and none breast-fed. Prematurity rate for the
      entire series was 19%. When women who actively used illicit drugs were excluded,
      only seven of 69 (10%) women were found to deliver prematurely. The use of
      protease inhibitors was limited by an elevated frequency of severe
      gastrointestinal disturbances. The rate of congenital malformations did not
      appear to differ significantly from that reported in the literature for the
      general population. Only one of 102 live newborns was found to be HIV-1-infected
      (1.0%, 95% confidence interval; 0.3-4.6%). CONCLUSIONS: The present findings
      confirm the remarkable efficacy of combination antiretroviral therapy, Caesarean
      section and refraining from breast-feeding in lowering the rate of vertical HIV-1
      transmission. Moreover, they are suggestive that combination antiretroviral
      therapy may not be related to major neonatal toxicity. The necessity to
      discontinue the therapy during the first trimester of pregnancy and to
      systematically incorporate zidovudine into combination regimens is discussed.

PMID- 11821292
TI  - Factor V Leiden and recurrent miscarriage-prospective outcome of untreated
      pregnancies.
AB  - BACKGROUND: Some cases of recurrent miscarriage and later pregnancy complications
      have a thrombotic basis. Factor V Leiden is a common thrombophilic mutation.
      METHODS: The prospective outcome of untreated pregnancies amongst 25 women
      heterozygous for the Factor V Leiden allele who had a history of either recurrent
      early miscarriages only (three or more miscarriages at <12 weeks gestation; n =
      19) or of late miscarriage (>12 weeks gestation; n = 9) was studied. Control
      groups of women with a similar pregnancy history but who had a normal Factor V
      genotype were also studied. RESULTS: The live birth rate was significantly lower
      amongst women with a history of recurrent early miscarriage who carried the
      Factor V Leiden allele (6/16; 37.5%) compared with that amongst those with a
      normal Factor V genotype (106/153; 69.3%; odds ratio 3.75, 95% confidence
      intervals 1.3-10.9). The live birth rate was 11.1% (1/9) amongst those with a
      history of late miscarriage carrying the Factor V Leiden allele and 48.9% (22/45)
      amongst those with a normal Factor V genotype. CONCLUSIONS: Attention should be
      directed at screening women with recurrent miscarriage associated with placental
      thrombosis for Factor V Leiden and a policy of targeted thromboprophylaxis during
      future pregnancies should be assessed in the form of a randomized controlled
      trial.

PMID- 11821293
TI  - Cytogenetic analysis of miscarriages from couples with recurrent miscarriage: a
      case-control study.
AB  - BACKGROUND: Reproductive loss carries immeasurable human costs as well as being
      costly to the health care system. The objectives of this study were to determine
      the frequency and distribution of cytogenetically abnormal miscarriages from
      couples with recurrent miscarriage and to compare the results with the general
      population. METHODS: A total of 420 specimens, including 29 pre-clinical, 237
      embryonic and 154 fetal, were successfully karyotyped from 285 couples with
      recurrent miscarriage. The results were stratified according to maternal age and
      compared with controls. RESULTS: In all, 225 specimens (54%) were euploid. A
      total of 195 specimens (46%) were cytogenetically abnormal, of which 131 (66.5%)
      were trisomic, 37 (19%) were polyploid, 18 (9%) were monosomy X, eight (4%) were
      unbalanced translocations and one was a combination of trisomy 21 and monosomy X.
      The frequency of euploid miscarriages was significantly higher in women <36 years
      of age with recurrent miscarriage compared with controls. The distribution of
      cytogenetic abnormalities in the recurrent miscarriage group was not
      significantly different from controls, when stratified by maternal age.
      CONCLUSIONS: Women <36 years of age with recurrent miscarriage have a higher
      frequency of euploid miscarriage. When stratified for maternal age, there is no
      difference in the distribution of cytogenetically abnormal miscarriages in
      couples with recurrent miscarriage compared with controls.

PMID- 11821294
TI  - Collection of villous tissue under ultrasound guidance to improve the cytogenetic
      study of early pregnancy failure.
AB  - BACKGROUND: The cytogenetic study of spontaneous miscarriage has been limited by
      poor karyotype success rates obtained from cell culture after surgical evacuation
      of retained products of conception. The aim of this study was to assess the
      effect of improving the method of collection of villous tissues at the time of
      surgery on the karyotype success rate of cell culture. METHODS: Villous samples
      were obtained prospectively from a cohort of 170 spontaneous miscarriages at the
      beginning of the surgical procedure using small biopsy forceps guided into the
      placenta by ultrasound imaging. This was compared with a retrospective series of
      1191 spontaneous miscarriages, cultured in the same laboratory, following
      conventional collection of the sample from the aspiration recipient after
      surgery. RESULTS: In the prospective series, six (3.5%) of the original samples
      were classified by the laboratory as 'decidua only' as compared with 162 (13.6%)
      in the retrospective series. The karyotype success rate was 94.5% in the
      prospective series compared with 83.7% in the retrospective series. The karyotype
      results revealed a chromosome abnormality rate of 65.8% in the prospective group
      and 64% in the retrospective group with a similar distribution in both groups.
      CONCLUSIONS: Our data show that a karyotype can be obtained from clean villous
      material collected at the time of surgical evacuation of miscarriage. Thus, it is
      not justified to subject women to transabdominal chorionic villus sampling to
      achieve a high karyotype success rate.

PMID- 11821295
TI  - Preimplantation exposure to high insulin-like growth factor I concentrations
      results in increased resorption rates in vivo.
AB  - BACKGROUND: Women with polycystic ovarian syndrome suffer increased rates of
      miscarriage. Elevated insulin and insulin-like growth factor I (IGF-I)
      concentrations have been implicated. Here, we hypothesize that the high
      concentrations of IGF-I result in miscarriage, represented by decreased normal
      pregnancy rates and increased resorption rates in a mouse model. METHODS: In
      vitro studies: 2-cell embryos were cultured in either 1.3 or 130 nmol/l IGF-I; or
      500 nmol/l IGF-I receptor (IGF-IR) sense and antisense oligoprobes for 72 h.
      Embryos were then transferred into pseudo-pregnant ICR females. In-vivo studies:
      IGF-I-containing slow-release pellets or mock pellets were implanted within the
      uterine horn in ICR female mice. For both studies, the recipient females were
      killed on day 14.5 and the numbers of normal implantation sites versus resorption
      sites were recorded. RESULTS: In-vitro studies: blastocysts cultured in low IGF-I
      exhibited significantly higher normal implantation rates than blastocysts
      cultured in high IGF-I concentrations (P < 0.01). Blastocysts cultured in IGF-IR
      sense oligoprobes exhibited a significantly higher normal implantation rate than
      blastocysts cultured in antisense oligoprobes. In-vivo studies: mice implanted
      with IGF-I-containing pellets exhibited significantly lower normal implantation
      rates as compared with mock-pellet controls (P < 0.01). CONCLUSIONS: High
      preimplantation IGF-I concentrations in vitro or in vivo lead to increased
      resorption rates in the mouse.

PMID- 11821296
TI  - Telomerase activity in gestational trophoblastic disease and placental tissue
      from early and late human pregnancies.
AB  - BACKGROUND: The aim of this study was to evaluate telomerase activity in tissue
      from cases of gestational trophoblastic disease (GTD) and in placental tissue
      from early and late human pregnancies. METHODS: We used a telomeric repeat
      amplification protocol assay to measure telomerase activity in 132 tissue samples
      from normal early pregnancies, spontaneous abortions, normal late pregnancies,
      cases of late-pregnancy intrauterine fetal death, and GTD. RESULTS: Telomerase
      activity was detected more often in normal early pregnancies and cases of GTD
      than in spontaneous abortions and normal late pregnancies (P < 0.001). During
      early gestation, no significant difference in detection rates was found between
      normal pregnancies and complete hydatidiform mole. As gestational age increased,
      detection rates for normal pregnancies decreased significantly (P = 0.0001),
      while for complete hydatidiform mole no significant changes occurred.
      CONCLUSIONS: Our findings indicate that placental tissue from normal early
      pregnancies and neoplastic tissue from GTD possess similar levels of telomerase
      activity. Decreasing regulation of telomerase activity is present in normal
      pregnancies but not in complete hydatidiform mole. The fact that telomerase
      activity decreases in cases of fetal demise, and as pregnancy progresses, also
      suggests that placental senescence may play a role in the development and ageing
      of the placenta.

PMID- 11821297
TI  - Outcome of subsequent pregnancy after treatment for persistent gestational
      trophoblastic tumour.
AB  - BACKGROUND: This study analysed subsequent pregnancy outcome in patients treated
      for persistent gestational trophoblastic tumour (GTT). METHODS: Between 1974 and
      1999, a total of 378 patients with GTT (83 patients with high-risk and 295
      patients with low-risk GTT) were treated at Chiba University Hospital, Japan. Of
      these 378 patients, 363 (96.0%) achieved primary remission and 315 survivors have
      been followed at our hospital. RESULTS: To date, 129 patients have had 243
      subsequent conceptions. While pregnancy outcome was comparable with that of the
      general Japanese population, the incidence of repeat molar pregnancy (2.1%) was
      approximately seven times higher than that of the general population. During the
      mandatory HCG follow-up period of 1 year, 15 patients conceived within 6 months
      of completion of chemotherapy. The incidence of spontaneous abortion in these 15
      patients was significantly higher than that in patients who conceived after a
      waiting period of >6 months (P = 0.0053). CONCLUSIONS: Patients treated for GTT
      may anticipate a normal future reproductive outcome, although it would be better
      to avoid pregnancy for at least 6 months after completion of chemotherapy.

PMID- 11821298
TI  - Peripheral blood mononuclear cells in early pregnancy promote invasion of human
      choriocarcinoma cell line, BeWo cells.
AB  - BACKGROUND: During the establishment of the maternal blood circulation around the
      implanting human embryo, maternal peripheral blood mononuclear cells (PBMC)
      directly contact trophoblasts. To determine the physiological significance of
      this interaction, the effects of PBMC obtained from pregnant women on the
      proliferative and invasive properties of a human choriocarcinoma cell line, BeWo
      cells, were examined. METHODS AND RESULTS: PBMC were obtained from women in early
      pregnancy and from women in the secretory phase of the menstrual cycle. PBMC from
      pregnant women significantly increased the number of invading BeWo cells in an
      invasion assay without affecting the proliferation of BeWo cells (P +/- 0.05). No
      significant changes were observed in the co-cultures with PBMC from non-pregnant
      women. The addition of conditioned medium, which was prepared by 2 days of
      incubation with PBMC from pregnant women, also enhanced BeWo cell invasion in a
      dose-dependent manner. Moreover, when PBMC obtained from non-pregnant women were
      incubated with recombinant HCG (0-10 IU/ml) for 2 days, significant augmentation
      of the effect on BeWo cell invasion was observed in the conditioned medium from
      HCG-treated PBMC (P +/- 0.05). CONCLUSION: This study indicated that soluble
      factor(s) secreted from PBMC promote BeWo cell invasion. It also showed the
      possible involvement of HCG in the regulation of BeWo cell invasion by PBMC.
      These findings suggest crosstalk between maternal PBMC and trophoblasts via
      soluble factor(s), which may play an important role in early embryo implantation.

PMID- 11821299
TI  - Serum free beta-HCG and alpha-fetoprotein levels in IVF, ICSI and frozen embryo
      transfer pregnancies in maternal mid-trimester serum screening for Down's
      syndrome.
AB  - BACKGROUND: The aim of this study was to compare the maternal mid-trimester free
      beta-HCG and alpha-fetoprotein (AFP) levels in pregnancies conceived by assisted
      reproduction technology and spontaneous pregnancies in Down's syndrome screening.
      The influence of the number of embryos transferred and the amount of
      gonadotrophins used on the marker levels was also evaluated. METHODS: The study
      population consisted of 58 IVF, 32 ICSI and 26 frozen embryo transfer (FET)
      singleton pregnancies. The levels of beta-HCG and AFP were compared with the
      control group of 6548 singleton spontaneous pregnancies. RESULTS: The false
      positive rate (FPR) in the Down's syndrome screening was 19% overall in assisted
      reproductive technology pregnancies, being highest (30.8%) in the FET group. The
      free beta-HCG multiples of the median (MoM) values were statistically
      significantly elevated only in the FET group (1.33 MoM; P = 0.012). A positive
      correlation between the number of embryos transferred and the marker levels was
      observed in the IVF group. No correlation was found between the amount of
      gonadotrophin medication used and the marker levels. CONCLUSIONS: The present
      data confirm that the overall FPR in the serum screening for Down's syndrome in
      assisted reproduction pregnancies is high, resulting in unnecessary invasive
      procedures.

PMID- 11821300
TI  - Maternal serum HCG is higher in the presence of a female fetus as early as week 3
      post-fertilization.
AB  - BACKGROUND: Maternal serum HCG (MSHCG) is higher when the fetus is a female than
      when it is male. This has been demonstrated in the second and third trimesters of
      pregnancy, and recently at 10-14 weeks gestation. In this study we assessed
      whether this gender-related difference can be detected as early as week 3 post
      fertilization. METHODS: The IVF setting was chosen because it provides precise
      dating of gestational age and early sonography for the number of gestational
      sacs. The study included 347 IVF cycles from 335 patients. Only pregnancies with
      a single implanted embryo that resulted in a single live birth of known gender
      were included. MSHCG was measured on days 14-20 post-fertilization, and levels
      were expressed as gestational age-corrected multiples of the median (MoMs). The
      log10 MSHCG MoMs were compared according to fetal gender. RESULTS: MSHCG levels
      were significantly higher (18.5%) in week 3 post-fertilization in the presence of
      a female fetus (P < 0.0002). CONCLUSION: Because a fetal gender-related
      difference in MSHCG can be demonstrated as early as week 3 post-fertilization,
      the difference may be attributed to placental factors and not to the effects of
      the fetal hypothalamic-hypophyseal-gonadal axis.

PMID- 11821301
TI  - Serum vascular endothelial growth factor as a possible marker for early ectopic
      pregnancy.
AB  - BACKGROUND: This study evaluated serum vascular endothelial growth factor (VEGF)
      concentrations in women with normal intrauterine pregnancy (IUP), arrested IUP
      and ectopic pregnancy (EP). METHOD: This was a prospective, case-control study
      evaluating serum VEGF concentrations among 45 early pregnant women who
      subsequently were found to have an EP, a normal IUP or an arrested IUP (15 women
      in each group). Patients were stratified according to serum VEGF concentrations
      above and below 200 pg/ml. RESULTS: There was a significant difference in VEGF
      concentrations among women with EP, arrested IUP and normal IUP (306.1 +/- 26.5,
      169.7 +/- 16.6 and 27.0 +/- 4.4 pg/ml respectively, P < 0.001). With a cut-off
      concentration of 200 pg/ml, serum VEGF could distinguish normal IUP from EP with
      a sensitivity of 88%, a specificity of 100% and a positive predictive value of
      100%. Between EP and arrested IUP, the sensitivity was 87.5%, specificity 75% and
      positive predictive value of 77.8%. CONCLUSIONS: VEGF is a potential marker for
      EP. Its concentrations in women with EP are higher than in those with normal and
      arrested IUP.

PMID- 11821302
TI  - Cervical Shirodkar cerclage may be the treatment modality of choice for cervical
      pregnancy.
AB  - BACKGROUND: Our objective was to evaluate the use of cervical suture in cervical
      pregnancy. METHODS AND RESULTS: All cases of cervical pregnancy diagnosed and
      treated in the gynaecological department at the Sheba Medical Center between 1994
      2000 were included in the study. Eight such cases were diagnosed. The first four
      cases were treated medically. The last four cases (the study group) of cervical
      pregnancy, including one case of heterotopic pregnancy, were treated successfully
      with placement of Shirodkar cerclage. CONCLUSION: Cervical cerclage may be
      considered as the treatment of choice in cases of cervical pregnancies. It may be
      the only therapy in cases of heterotopic pregnancies (intrauterine and cervical
      pregnancy).

PMID- 11821303
TI  - Hormone replacement therapy can augment vascular relaxation in post-menopausal
      women with type 2 diabetes.
AB  - BACKGROUND: Diabetes is a major risk factor for coronary heart disease in women
      and event rates increase substantially after the menopause. Observational studies
      have suggested that estrogens may provide cardioprotection by regulating
      endothelial nitric oxide synthase. METHODS: In order to examine the effect of
      hormone replacement therapy (HRT) on endothelium-dependent and -independent
      vascular relaxation in post-menopausal women with type 2 diabetes, an open study
      was conducted in which gluteal biopsies were collected from 17 women before and
      after 6 months of transdermal 17 beta-estradiol (80 microg twice weekly) in
      combination with oral norethisterone (1 mg daily). Small arteries (<550 microm)
      were dissected from fat and mounted on a wire myograph for assessment of
      relaxation in response to acetylcholine (ACh), bradykinin (BK) and sodium
      nitroprusside (SNP). RESULTS: Maximal relaxation responses to ACh, BK and SNP in
      women with diabetes and non-diabetic control subjects were 52 +/- 8 versus 96 +/-
      2% (P < 0.05), 76 +/- 7 versus 97 +/- 1%, (P < 0.05) and 91 +/- 2 versus 98 +/-
      1% (P < 0.05) respectively. After 6 months of HRT, maximal relaxation responses
      to ACh, BK and SNP in women with diabetes (compared with pre-HRT) were: 88 +/- 4
      (P < 0.05), 93 +/- 3 (P < 0.05) and 98 +/- 1% (P < 0.05) respectively. At
      baseline and after HRT, EC50 (concentration required to obtain 50% of maximum
      response) data exhibited similar changes. CONCLUSIONS: HRT had potentially
      beneficial effects on vascular relaxation. Data were consistent with improvements
      in endothelial function, vascular smooth muscle function, or both. Controlled
      studies are required to confirm and extend these findings.

PMID- 11821304
TI  - Time to pregnancy and semen parameters: a cross-sectional study among fertile
      couples from four European cities.
AB  - BACKGROUND: In fertile populations, little is known about the association between
      semen parameters and time to pregnancy (TTP). METHODS: Pregnant women from
      Copenhagen, Edinburgh, Paris and Turku who conceived without medical intervention
      were asked for their TTP (942 couples), and their partners provided a semen
      sample. The proportion of morphologically normal sperm and the multiple anomalies
      index (MAI, ratio of the total number of anomalies to the number of abnormal
      sperm) were centrally estimated. We estimated rate ratios for the occurrence of a
      pregnancy by a discrete survival model, adjusted for sexual activity and female
      factors affecting fecundity. RESULTS: Increasing sperm concentration influenced
      TTP up to 55 x 10(6)/ml. The proportion of morphologically normal sperm
      influenced TTP up to 39% according to David's criteria, and this association held
      among the subjects with a sperm concentration >55 x 10(6)/ml. For strict
      criteria, the threshold value was 19% normal sperm. An increase of 0.5 in MAI was
      associated with an adjusted rate ratio for the occurrence of a pregnancy of 0.68
      (95% confidence interval: 0.54-0.85). CONCLUSIONS: These results highlight the
      importance of sperm morphology parameters and indicate that the effect of
      proportion of normal sperm on TTP may be independent of sperm concentration.

PMID- 11821305
TI  - The potential value of mid-follicular phase LH.

PMID- 11821306
TI  - PGD and sex selection.

PMID- 11821308
TI  - Myths about endocrine disruption and the male reproductive system should not be
      propagated.

PMID- 11821311
TI  - Public health and data protection: an inevitable collision or potential for a
      meeting of minds?

PMID- 11821310
TI  - Ovarian artery resistance index as a marker of pituitary suppression.

PMID- 11821312
TI  - Advocacy in public health: roles and challenges.

PMID- 11821313
TI  - On the importance--and the unimportance--of birthweight.
AB  - Birthweight is one of the most accessible and most misunderstood variables in
      epidemiology. A baby's weight at birth is strongly associated with mortality risk
      during the first year and, to a lesser degree, with developmental problems in
      childhood and the risk of various diseases in adulthood. Epidemiological analyses
      often regard birthweight as on the causal pathway to these health outcomes. Under
      this assumption of causality, birthweight is used to explain variations in infant
      mortality and later morbidity, and is also used as an intermediate health
      endpoint in itself. Evidence presented here suggests the link between birthweight
      and health outcomes may not be causal. Methods of analysis that assume causality
      are unreliable at best, and biased at worst. The category of 'low birthweight' in
      particular is uninformative and seldom justified. The main utility of the
      birthweight distribution is to provide an estimate of the proportion of small
      preterm births in a population (although even this requires special analytical
      methods). While the ordinary approaches to birthweight are not well grounded, the
      links between birthweight and a range of health outcomes may nonetheless reflect
      the workings of biological mechanisms with implications for human health.

PMID- 11821314
TI  - Commentary: Birthweights and bell curves.

PMID- 11821315
TI  - Commentary: When brilliant insights lead astray.

PMID- 11821317
TI  - Statistical research on conditions caused by calculi by Doctor Civiale. 1835.

PMID- 11821318
TI  - Commentary: The Paris Academy of Science report on Jean Civiale's statistical
      research and the 19th century background to evidence-based medicine.

PMID- 11821319
TI  - Commentary: That was then, this is now.

PMID- 11821320
TI  - Commentary: 'Medical art' versus 'medical science': J Civiale's statistical
      research on conditions caused by calculi at the Paris Academy of Sciences in
      1835.

PMID- 11821321
TI  - Commentary: Treatment of bladder stones and probabilistic reasoning in medicine:
      an 1835 account and its lessons for the present.

PMID- 11821322
TI  - Welfare X = Y. 1960.

PMID- 11821323
TI  - The role of medical care in contributing to health improvements within societies.

PMID- 11821324
TI  - Commentary: Can health outputs of routine practice approach those of clinical
      trials?

PMID- 11821325
TI  - Commentary: Medical care and the wider influences upon population health: a false
      dichotomy.

PMID- 11821326
TI  - Recent trend of increase in proportion of low birthweight infants in Japan.
AB  - BACKGROUND: The proportion of low birthweight babies (LBW: 1500-2499 g) in Japan
      decreased steadily from 1950 to the 1970s. However, since then it has started to
      increase consistently, the reason for which has not been discussed in detail.
      METHODS: Trends of birthweight and the two known factors for low birthweight
      (maternal smoking, and pre-pregnancy weight) were analysed with vital statistics,
      national nutritional and smoking prevalence survey data. RESULTS: Increase in
      term LBW due to intrauterine growth retardation, is the major risk factor for the
      overall increase since the 1970s. The increase of smoking prevalence in women in
      their thirties started in the 1970s, while that for women in their twenties
      started in the 1960s. The decrease of body mass index for women in their thirties
      also began in the 1970s, while that for women in their twenties began in the
      1960s. The ratio of delivery to mothers in their thirties to mothers in their
      twenties has increased more than threefold compared to the late 1970s.
      CONCLUSIONS: Since the 1970s increase in smoking prevalence and decrease in body
      mass index in young women, especially those in their thirties, appeared to be the
      major factors involved in the increase in LBW babies.

PMID- 11821327
TI  - Birthweight in a fishing community: significance of essential fatty acids and
      marine food contaminants.
AB  - BACKGROUND: Marine food provides essential fatty acids that are important during
      pregnancy, but the benefits may be limited at high intakes and by seafood
      contaminants. METHODS: In the fishing community of the Faroe Islands, 182
      pregnant women with spontaneous singleton births were consecutively recruited for
      a cohort in 1994- 1995. Concentrations of fatty acids and seafood contaminants in
      blood samples were analysed as predictors of gestational length and birthweight.
      RESULTS: Serum concentrations of eicosapentaenoic acid (EPA) increased with
      maternal marine food intake, while the tendency was less clear for
      docosahexaenoic acid (DHA). An increase in the relative concentration of DHA in
      cord serum phospholipids by 1% was associated with an increased duration of
      gestation by 1.5 days (95% CI : 0.7-2.2). However, birthweight adjusted for
      gestational length decreased by 246 g (95% CI : 16-476) for each increase by 1%
      of the EPA concentration in cord serum. Concentrations of the seafood pollutants
      mercury and polychlorinated biphenyls (PCB) were associated with fatty acids
      levels, but the contaminants did not appear to affect any of the outcome
      parameters. CONCLUSION: An increased intake of marine fats appears to prolong the
      duration of gestation, but birthweight adjusted for gestational age may decrease
      at high intake levels. This effect does not seem to be due to increased exposures
      to seafood contaminants.

PMID- 11821328
TI  - Commentary: Mercury, PCB, and now eicosapentaenoic acid: still another reason why
      pregnant women should be concerned about eating seafood?

PMID- 11821329
TI  - Incidence of appendicitis during pregnancy.
AB  - BACKGROUND: The aetiology and pathogenesis of appendicitis remains unknown. A
      relation with female sex hormones has been proposed because of a lower incidence
      among women and incidence variations during the menstrual cycle, but studies have
      given inconsistent results. Pregnancy constitutes a period of dramatic increases
      in levels of female sex hormones, but the incidence of appendicitis during
      childbearing is not known. METHODS: Case-control study of pregnancy status at the
      time of appendectomy of 53 058 women and of 53 058 population-based age-matched
      controls. Cases and controls were identified by linkage of the Swedish Inpatient
      Register and the nation-wide census. Pregnancy status at the time of operation
      was obtained by linkage with the Swedish Fertility Register. Differences in
      pregnancy status were analysed using conditional logistic regression and
      expressed as odds ratios (OR) with 95% CI. RESULTS: Fewer patients than expected
      with appendicitis were pregnant compared with the controls, especially in the
      third trimester (OR = 0.49, 95% CI : 0.30-0.79 for perforated and OR = 0.33, 95%
      CI : 0.28-0.39 for non-perforated appendicitis). CONCLUSIONS: The reduced
      incidence of appendicitis suggests a protective effect of pregnancy, especially
      in the third trimester.

PMID- 11821330
TI  - Decline of infant and child mortality rates in rural Senegal over a 37-year
      period (1963-1999).
AB  - BACKGROUND: In spite of an improving trend, childhood mortality in rural sub
      Saharan Africa remains high and has recently risen in some countries. The factors
      associated with the long-term decline in childhood mortality are poorly known,
      due to a lack of data. METHODS: A Senegalese rural population has been under
      demographic surveillance since 1963. Infant and under-5 mortality rates were
      calculated for different periods to generate a long-term trend in childhood
      mortality. Evolution of age and seasonal patterns of mortality were observed.
      FINDINGS: During the observation period (1963-1999), infant and under-5 mortality
      rates decreased from 223 per thousand to 80 per thousand and 485 per thousand to
      213 per thousand , respectively, with a constant annual rate of decline in the
      probability of dying since the 1960s (-3.7% and -3.1%, respectively). The age
      pattern of the under-5 mortality changed drastically, with a large decrease in
      the death rate between 6 and 24 months of age (from 321 per thousand to 87 per
      thousand ). This change took place during the 1970s. The seasonal variation,
      characterized by a greater proportion of deaths during the rainy season, was very
      marked during the 1960s, then decreased during the 1980s but it has tended to
      increase again in the 1990s, particularly among children 1-4 years old.
      CONCLUSION: This study confirms the long-term trend of decrease in child
      mortality in rural West Africa. Historical knowledge on healthcare developments
      suggests that immunizations have contributed to the decrease and the change in
      the age pattern. The re-emergence of malaria seems the most likely explanation
      for the recent rebound in seasonal variation. Attention to immunization and
      malaria should continue to be a priority.

PMID- 11821332
TI  - The influence of socioeconomic status on stillbirth risk in Sweden.
AB  - BACKGROUND: Low socioeconomic status (SES) is generally associated with increased
      risk of stillbirth, but the mechanisms have rarely been investigated. Our aim was
      to study the association between SES and risk of stillbirth, and to assess
      whether any differences in risk are mediated by other maternal socio-demographic
      or anthropometrical characteristics, differences in lifestyle, or attendance at
      antenatal care. METHODS: Population-based individually-matched case-control study
      including 702 cases of stillbirth and 702 controls among Swedish primiparous
      women giving birth 1987-1996. We estimated the risk of stillbirth, and subgroups
      of stillbirth, for various categories of SES. Odds ratios (OR) with 95% CI,
      estimated by conditional logistic regression, were used to approximate the
      relative risk. The estimates were adjusted for maternal age, height, body mass
      index, cigarette smoking, and when necessary mother's country of birth. RESULTS:
      Compared with women who were high level white-collar workers, the adjusted risks
      of stillbirth were as follows: unskilled blue-collar workers, 2.2 (95% CI : 1.3-
      3.7), skilled blue-collar workers, 2.4 (95% CI : 1.3-4.1), low level white-collar
      workers, 1.9 (95% CI : 1.2-3.2), and intermediate level white-collar workers 1.4
      (95% CI : 0.9-2.4). These risks were not substantially changed when we further
      adjusted for attendance at antenatal care, previous reproductive history, or
      excluded pregnancies with maternal diseases, and pregnancy-related disorders. Low
      social class was most associated with risks of term antepartum and intrapartum
      stillbirths. CONCLUSIONS: Low SES increases the risk of stillbirth. The
      association could not be explained by any of the factors we studied, and the
      underlying reasons remain unclear.

PMID- 11821333
TI  - Commentary: Social inequalities in risk of stillbirth--the price of success?

PMID- 11821334
TI  - Effect of prenatal treatment on mother to child transmission of Toxoplasma
      gondii: retrospective cohort study of 554 mother-child pairs in Lyon, France.
AB  - BACKGROUND: The aim of prenatal serological screening for toxoplasmosis is to
      identify and treat maternal infection as soon as possible in order to prevent
      transmission of the parasite to the fetus. However, despite widespread provision
      of prenatal toxoplasma screening across Europe, the effectiveness of prenatal
      treatment is uncertain. The study aimed to determine the effect of the timing and
      type of prenatal treatment on mother to child transmission of Toxoplasma gondii.
      METHOD: A cohort of 554 infected pregnant women were identified in Lyon, France
      between 1987 and 1995 and their children were followed to determine congenital
      infection status. We determined the effect of prenatal treatment on transmission
      by examining the effect of the delay between maternal seroconversion and start of
      treatment. We also compared the effect of the type of treatment and no treatment
      on the risk of mother to child transmission. Analyses were adjusted for gestation
      at maternal seroconversion. RESULTS: Compared to treatment within 4 weeks from
      seroconversion, the adjusted odds ratios (OR) for mother to child transmission
      after a treatment delay of 4-7 weeks was 1.29 (95% CI : 0.61, 2.73) and after
      more than 8 weeks, 1.44 (95% CI : 0.60, 3.31). The adjusted OR associated with
      spiramycin alone compared with pyrimethamine-sulfadiazine treatment was 0.91 (95%
      CI : 0.45, 1.84) and the OR for no treatment compared with pyrimethamine
      sulfadiazine treatment was 1.06 (95% CI : 0.37, 3.03). CONCLUSIONS: The authors
      hypothesize that the absence of an effect of prenatal treatment is due to
      transmission before the start of treatment.

PMID- 11821335
TI  - Effect of prenatal treatment on the risk of intracranial and ocular lesions in
      children with congenital toxoplasmosis.
AB  - BACKGROUND: Hydrocephalus, intracranial calcification and retinochoroiditis are
      the most common manifestations of tissue damage due to congenital toxoplasmosis,
      but the effect of prenatal treatment on these outcomes is unclear. We aimed to
      determine the effect of prenatal treatment for toxoplasmosis on the risk of
      intracranial and ocular lesions in congenitally infected children at 3 years of
      age. METHODS: A cohort of mothers identified during pregnancy with toxoplasma
      infection and their 181 liveborn children with confirmed congenital toxoplasmosis
      was retrospectively analysed to determine the presence of intracranial and ocular
      lesions. As few women are not treated, we compared the effects of the treatment
      potency (pyrimethamine-sulfadiazine versus spiramycin or no treatment), and the
      timing of treatment, on the risks of intracranial lesions, time to detection of
      ocular lesions, and detection of any lesions (intracranial or ocular) by 3 years
      of age. Analyses took account of the gestation at maternal seroconversion.
      RESULTS: There was no evidence for an effect of pyrimethamine-sulfadiazine on
      intracranial, ocular or any lesions by 3 years: odds ratio (OR) for any lesions
      0.89 (95% CI : 0.41, 1.88). There was no evidence of an effect of delayed
      treatment on ocular lesions (hazard ratio = 0.69, 95% CI : 0.28, 1.68) or any
      lesions by 3 years of age (OR = 0.44, 95% CI : 0.16, 1.19). CONCLUSIONS: Our
      study failed to detect a beneficial effect of early or more potent anti
      toxoplasma treatment on the risks of intracranial or ocular lesions in children
      with congenital toxoplasmosis. However, larger, prospective studies, which
      determine the effect of prenatal treatment on long-term developmental outcomes
      are required to justify changes in clinical practice.

PMID- 11821336
TI  - Commentary: Little evidence of effective prenatal treatment against congenital
      toxoplasmosis--the implications for testing in pregnancy.

PMID- 11821337
TI  - Commentary: Efficacy of prenatal treatment for toxoplasmosis: a possibility that
      cannot be ruled out.

PMID- 11821338
TI  - Changing paternity and time since last pregnancy; the impact on pre-eclampsia
      risk. A study of 547 238 women with and without previous pre-eclampsia.
AB  - BACKGROUND: Long time interval between pregnancies has been found to increase the
      risk of pre-eclampsia in second pregnancy. Our aim was to investigate whether
      this effect is influenced by a history of pre-eclampsia or a change in paternity.
      METHODS: We studied 547 238 women with a first and second pregnancy registered in
      the Medical Birth Registry of Norway, 1967-1998. The relative risk of pre
      eclampsia in the second delivery according to time interval between deliveries
      was estimated as odds ratios (OR) in logistic regression models, controlling for
      changing paternity, maternal age and calendar time period in women with and
      without previous pre-eclampsia. RESULTS: A change of paternity for the second
      pregnancy was associated with a reduced risk of pre-eclampsia after controlling
      for the time since first delivery (adjusted OR = 0.80, 95% CI : 0.72-0.90), but
      the interaction between change in paternity and time between deliveries was
      significant only for women with no previous pre-eclampsia. The interaction
      between history of pre-eclampsia and time interval between the two deliveries was
      highly significant, and for women with no previous pre-eclampsia the risk of pre
      eclampsia in second pregnancy increased with increasing time interval (for
      intervals longer than 15 years the adjusted OR was 2.11, 95% CI : 1.75-2.53). For
      women with previous pre-eclampsia the risk tended to decrease with increasing
      time interval between deliveries. CONCLUSIONS: The protective impact of a new
      father for the second pregnancy challenges the hypothesis of primipaternity, and
      implies that the increase in pre-eclampsia risk ascribed to new father by others
      is due to insufficient control for interpregnancy interval.

PMID- 11821339
TI  - Commentary: Revisiting the primipaternity theory of pre-eclampsia.

PMID- 11821340
TI  - Short-term benefits of catch-up growth for small-for-gestational-age infants.
AB  - BACKGROUND: Recent studies suggest that small newborns who present rapid
      postnatal growth may have an increased risk of chronic diseases in adulthood. On
      the other hand, it is widely assumed that catch-up growth is desirable for low
      birthweight children, but the literature on this subject is limited. METHODS:
      Population-based cohort study in southern Brazil, with 3582 children examined at
      birth, 20 and 42 months of age. Catch-up growth from 0 to 20 months was related
      to subsequent risks of hospital admissions and mortality. RESULTS: Children who
      were small-for-gestational-age (SGA) but presented substantial weight gain (> or
      =0.66 z-score) up to the age of 20 months had 65% fewer subsequent hospital
      admissions than other SGA children (5.6% versus 16.0%; P < 0.001). Mortality to
      age 5 years was 75% lower (3 versus 13 per 1000, a non-significant difference
      based on a small number of deaths) for rapid-growing SGA children compared to the
      remaining SGA children. Their admission and mortality rates were similar to those
      observed for children born with an appropriate birthweight for their gestational
      age (AGA). Similar positive effects of rapid growth were found for AGA children.
      CONCLUSION: There appear to be definite benefits associated with catch-up growth.
      Growth promotion efforts for infants who are born small should take into account
      their possible short- and long-term consequences.

PMID- 11821341
TI  - Commentary: Early 'catch-up' growth is good for later health.

PMID- 11821342
TI  - Tutorial in Biostatistics: Evaluating the impact of 'critical periods' in
      longitudinal studies of growth using piecewise mixed effects models.
AB  - Recent developments in modern multivariate methods provide applied researchers
      with the means to address many important research questions that arise in studies
      with repeated measures data collected on individuals over time. One such area of
      applied research is focused on studying change associated with some event or
      critical period in human development. This tutorial deals with the use of the
      general linear mixed model for regression analysis of correlated data with a two
      piece linear function of time corresponding to the pre- and post-event trends.
      The model assumes a continuous outcome is linearly related to a set of
      explanatory variables, but allows for the trend after the event to be different
      from the trend before it. This task can be accomplished using a piecewise linear
      random effects model for longitudinal data where the response depends upon time
      of the event. A detailed example that examines the influence of menarche on
      changes in body fat accretion will be presented using data from a prospective
      study of 162 girls measured annually from approximately age 10 until 4 years post
      menarche.

PMID- 11821343
TI  - Commentary: Are piecewise mixed effects models useful in epidemiology?

PMID- 11821344
TI  - Ecologic versus individual-level sources of bias in ecologic estimates of
      contextual health effects.
AB  - A number of authors have attempted to defend ecologic (aggregate) studies by
      claiming that the goal of those studies is estimation of ecologic (contextual or
      group-level) effects rather than individual-level effects. Critics of these
      attempts point out that ecologic effect estimates are inevitably used as
      estimates of individual effects, despite disclaimers. A more subtle problem is
      that ecologic variation in the distribution of individual effects can bias
      ecologic estimates of contextual effects. The conditions leading to this bias are
      plausible and perhaps even common in studies of ecosocial factors and health
      outcomes because social context is not randomized across typical analysis units
      (administrative regions). By definition, ecologic data contain only marginal
      observations on the joint distribution of individually defined confounders and
      outcomes, and so identify neither contextual nor individual-level effects. While
      ecologic studies can still be useful given appropriate caveats, their problems
      are better addressed by multilevel study designs, which obtain and use individual
      as well as group-level data. Nonetheless, such studies often share certain
      special problems with ecologic studies, including problems due to inappropriate
      aggregation and problems due to temporal changes in covariate distributions.

PMID- 11821345
TI  - Estimation of the incidence of stroke using a capture-recapture model including
      covariates.
AB  - BACKGROUND: Capture-recapture is often used to assess completeness of a register.
      However, the usual two-source model relies on assumptions of independence of
      sources and equality of capture probability which are rarely satisfied in
      epidemiology. An alternative is to include covariates in capture-recapture
      models. METHODS: We use capture-recapture models including covariates to estimate
      incidence of stroke in South London. We estimate ascertainment-adjusted age
      standardized incidence rates, and calculate confidence intervals for incidence
      which allow for the uncertainty in estimation of the total number of cases.
      RESULTS: The crude capture-recapture model (including no covariates)
      underestimated the number of non-fatal strokes. Demographic and stroke severity
      variables were associated with the probability of capture. Including covariates
      led to more plausible results for fatal and non-fatal strokes, and suggested that
      the stroke register was 88% complete. Adjusting for under-ascertainment increased
      the estimated incidence from 1.31 (95% CI : 1.21-1.42) to 1.49 (95% CI : 0.38
      2.60) per 1000 people. CONCLUSIONS: Incidence and age-standardized incidence can
      be calculated using data from an incomplete register. However, sparse strata can
      lead to wide confidence intervals for adjusted rates. Cost-effectiveness of
      routine registers might be increased by using the combination of sources and
      covariates which most accurately estimates the total number of cases, rather than
      by aiming for 100% completeness.

PMID- 11821348
TI  - Commentary: Measuring physical activity in Sub-Saharan Africa.

PMID- 11821347
TI  - Development and validation of a questionnaire for the assessment of physical
      activity in epidemiological studies in Sub-Saharan Africa.
AB  - OBJECTIVE: To develop and validate a questionnaire for measuring physical
      activity within Sub-Saharan Africa. Methods We designed the Sub-Saharan Africa
      Activity Questionnaire (SSAAQ), based upon existing questionnaires and an
      activity survey carried out in Cameroon. The questionnaire targeted past-year
      occupation, walking/cycling and leisure-time activities, and was administered by
      trained interviewers on two occasions, 10-15 days apart to 89 urban and rural
      consenting Cameroonians aged 19-68 years. Reliability was assessed by inter
      interview comparison and repeatability coefficients (standard deviation of the
      test-retest difference). Validation was performed against a 24-hour heart rate
      monitoring and accelerometer recording. RESULTS: The questionnaire was highly
      reproducible (rho = 0.95; P < 0.001). The inter-interview difference did not
      differ significantly from 0, with a repeatability coefficient of 0.46-1.46 hours.
      Total energy expenditure from the questionnaire was significantly correlated to
      heart rate monitoring (rho = 0.41-0.63; P < 0.05) and accelerometer measures (rho
      = 0.60-0.74; P < 0.01). Subject's self ranking of their activity did not match
      the questionnaire's quartiles of activity. CONCLUSIONS: The present study
      presents the design and confirms the reliability and validity of SSAAQ in a rural
      and urban population of Cameroon and shows that subject's self ranking of
      activity might not accurately serve epidemiological purpose.

PMID- 11821349
TI  - Validation of self-reported hearing loss. The Blue Mountains Hearing Study.
AB  - PURPOSE: Large-scale epidemiological studies have often used self-report to
      estimate prevalence of age-related hearing loss. However, few large population
      based studies have validated self-report against measured hearing loss. Our study
      aimed to assess the performance of a single question and a brief hearing handicap
      questionnaire in identifying individuals with hearing loss, against the gold
      standard of pure-tone audiometry. METHODS: We examined 2015 residents, aged 55-99
      years, living in the west of Sydney, Australia, who participated in the Blue
      Mountains Hearing Study during 1997-1999. Audiologists administered a
      comprehensive questionnaire, including the question: 'Do you feel you have a
      hearing loss?' The Shortened Hearing Handicap Inventory for Elderly (HHIE-S) was
      also administered during the hearing examination, which included pure-tone
      audiometry. The single question and HHIE-S were compared with measured losses at
      levels >25, >40 and >60 decibels hearing level (dBHL) to indicate mild, moderate
      and marked hearing impairment, for pure-tone averages (PTA) of responses to 500,
      1000, 2000 and 4000 Hz. RESULTS: The single question yielded reasonable
      sensitivity and specificity for hearing impairment, and was minimally affected by
      age and gender. HHIE-S scores >8 had lower sensitivity but higher specificity and
      positive predictive value. The HHIE-S performed slightly better in younger than
      older subjects and performed better for moderate hearing impairment. CONCLUSIONS:
      In this older population with a high prevalence of hearing loss (39.4%), both a
      question about hearing and the HHIE-S appeared sufficiently sensitive and
      specific to provide reasonable estimates of hearing loss prevalence. Both could
      be recommended for use in epidemiological studies that aim to assess the
      magnitude of the burden caused by age-related sensory impairment but cannot
      measure hearing loss by audiometry.

PMID- 11821350
TI  - Regression models for unconstrained, partially or fully constrained continuation
      odds ratios.
AB  - Epidemiologists frequently encounter studies with ordered responses. Standard
      ordered response logit models, such as the continuation ratio model, constrain
      exposure to have a homogeneous effect across thresholds of the ordered response.
      We demonstrate a method for fitting regression models for unconstrained,
      partially or fully constrained continuation odds ratios using a 'person
      threshold' data set. For each subject, we create a separate record for each
      response threshold the subject is 'at risk' of passing and then apply standard
      binary logistic regression to estimate the continuation-ratio model. An example
      demonstrates the unconstrained, partially and fully constrained continuation
      ratio model, while a small simulation study examines some properties of the
      proposed 'person-threshold' approach. Finally, we present a brief discussion of
      statistical software to implement the method.

PMID- 11821351
TI  - Cognition and survival: an exploration in a large multicentre study of the
      population aged 65 years and over.
AB  - BACKGROUND: Understanding the patterns in determinants of survival becomes
      increasingly important as the population ages. Dementia is known to shorten
      survival as is impaired cognition. Whether this is a continuous phenomenon and
      independent of other explanatory variables is less clear. OBJECTIVES: To examine
      a population-based dataset in which a measure of cognitive function (Mini-Mental
      State Examination [MMSE]), self-reported physical health and lifestyle variables
      were measured at outset, with monitoring for mortality thereafter. METHODS: The
      five identical sites of the Medical Research Council Cognitive Function and
      Ageing Study (MRC CFAS) were analysed, with populations in rural Cambridgeshire,
      Gwynedd, Newcastle, Nottingham and Oxford. Survival curves were modelled and
      stratified analyses carried out, with physical disease, sociodemographic
      variables and lifestyle variables as covariates. RESULTS: There was a strong and
      consistent reduction in survival probability for each decrement in MMSE.
      Adjustment for known confounders did not alter this pattern. Social class and
      education in particular had no additional effect. Self-reported health was the
      only other associated variable. CONCLUSION: Cognitive function appears to be a
      marker of capacity for survival in the UK. Terminal decline can account for some
      of this. Actuarial survival provided here can give carers and service providers
      an idea of prognosis at given ages and levels of cognition, and provide baseline
      data for those planning interventions in similar groups.

PMID- 11821352
TI  - A 3-year follow-up study of social, lifestyle and health predictors of cognitive
      impairment in a Chinese older cohort.
AB  - BACKGROUND: Longitudinal data on the older population in the Asian setting are
      limited. This paper reports the factors associated with the development of
      cognitive impairment (CI) in a cohort of Chinese elderly aged > or =70 years.
      METHODS: The study cohort comprising 2030 subjects aged > or =70 years was
      assembled in 1991-1992 and followed for 36 months. Baseline information on
      cognitive function, as well as a number of social and health variables were
      obtained through face-to-face interview at the respondent's place of residence.
      The outcome variable was the development of CI among 988 cohort members who were
      initially free from CI, and who could be contacted at the 36-month follow-up. The
      instrument used to assess CI was based on the information/orientation part of the
      Clifton Assessment Procedure for the elderly (CAPE), using a cut-off point of 7.
      RESULTS: Of the men, 6.7%, but 22.2% of women had CI at 3-year follow-up. The age
      adjusted annual incidence of CI was 1.52% in men, and 6.37% in women.
      Multivariate logistic regression analysis showed that women had a 2.5-fold
      increased risk of having CI, compared with men. The risk increased by about 1.5
      fold with every 5-year increase in age. Slow gait time, as assessed by the 16
      foot walk, was a predictor of CI in both sexes (odds ratio [OR] = 1.03 per second
      increase, 95% CI : 1.0-1.07). Men residing in institutions had a 4.4-fold
      increased risk of having CI (95% CI : 1.7-11.1) compared with those residing in
      community, while the OR among women was 2.5 (95% CI : 1.3-4.9). Among women, no
      formal education increased the risk of having CI by 3.2-fold (95% CI : 1.8-5.5).
      Income dependency also increased the risk of CI by about fourfold, and no
      exercise at baseline was associated with a twofold increased risk of CI. Incident
      stroke during follow-up also increased the risk of CI (OR = 8.4, 95% CI : 1.2
      59.4). CONCLUSIONS: Older age and female sex were independent factors associated
      with CI. No formal education, slow gait time and institutionalization increased
      the risk of CI in both sexes. While education had a stronger effect in women,
      institutionalization had a stronger effect in men. Financial dependency, lack of
      exercise and incident stroke played a significant role in women.

PMID- 11821353
TI  - Income differences in mortality: a register-based follow-up study of three
      million men and women.
AB  - OBJECTIVES: We analyse whether the relationship between net household income and
      mortality form a continuous linear gradient or is curvilinear, assess the
      attenuation of this association after adjusting for confounding and reverse
      causality, and assess the strength of the association by age and cause of death.
      DESIGN AND SETTING: Prospective study of mortality in Finland among all men and
      women over 30 years old. Information on household income and sociodemographic
      factors was from the records of the Finnish tax authorities and the 1990 census.
      Income data were available for more than 95% of the cohort. Follow-up was by
      record linkage to death certificates in 1991-1996; altogether about 261 000
      deaths. RESULTS: The all-cause mortality ratio between the lowest and the highest
      household income decile is 2.37 (95% CI : 2.30-2.44) among men and 1.73 (95% CI :
      1.67-1.80) among women. Adjusting for household structure, spouse's economic
      activity, social class, education and own economic activity attenuates the
      relationship by 61% among men and 52% among women. The association between income
      and mortality is mainly linear before and after adjusting for confounding, and
      the association is strong for all 5-year age groups below 60-64 years, after
      which it declines rapidly in strength. CONCLUSIONS: The mainly linear nature of
      the relationship and the strong attenuation after adjustment for other
      socioeconomic factors and economic activity status, and the age pattern of the
      relationship indicate that a large part of the relationship is unlikely to be due
      to direct causal effects of poverty and material hardship. Rather, income seems
      to be related to accumulation of factors that increase mortality over the whole
      range of incomes.

PMID- 11821354
TI  - Commentary: Income and health: why are curves so appealing?

PMID- 11821355
TI  - The validity of self-reported use of health care across socioeconomic strata: a
      comparison of survey and registration data.
AB  - BACKGROUND: Socioeconomic differences in health and in use of health care are
      well known. Most data on socioeconomic differences in health care utilization are
      based on retrospective self-report in community surveys, but the evidence on the
      validity of self-reported utilization of health care across socioeconomic groups
      is limited. The aim of this study was to assess the validity of self-reported
      utilization of health care across socioeconomic groups in the general population.
      METHODS: We compared the concordance of self-reported and registered
      hospitalization (one year, n = 1277), and utilization of physiotherapy (one year,
      n = 1302) and use of prescription drugs (3 months, n = 899), by socioeconomic
      group (educational level, income, occupational status). Data came from a face-to
      face health interview survey in Amsterdam and a health insurance register, and
      were limited to native Dutch and lower and middle income groups. RESULTS:
      Concordance between reported and registered utilization was generally good to
      excellent; kappas (agreement adjusted for chance agreement) and percentage
      accurately reporting ranged from 0.60 and 80% (drugs) to 0.80 and 96%
      (hospitalization). They differed little, and without statistical significance,
      between people of low socioeconomic status and others. Assessment of
      socioeconomic groups in more detail yields somewhat more variation, but no
      systematic trend in concordance by higher socioeconomic status. CONCLUSION: Self
      report offers a reasonably valid estimate of differences in utilization of health
      care between socioeconomic groups in the general population, at least for lower
      and middle income groups.

PMID- 11821356
TI  - Oesophageal and gastric cardia adenocarcinomas: analysis of regional variation
      using the Cancer Incidence in Five Continents database.
AB  - BACKGROUND: Adenocarcinomas of the oesophagus and proximal stomach are the most
      rapidly increasing malignancies in some countries; however, there are no
      comparative studies on global disease incidence, and the relationships between
      these two malignancies are undefined. METHODS: We evaluated the cumulative rates
      and age-specific incidence rates per 100 000 population for adenocarcinomas of
      the oesophagus and proximal stomach for all countries in the Cancer Incidence in
      Five Continents database, and compared them with rates for oesophageal squamous
      cell carcinoma. RESULTS: Substantial variations in cumulative cancer rates were
      found between genders, between countries, between different ethnicities within
      the same country, and within the same ethnicity residing in different countries.
      Cumulative rates (ages 0-74 years) for oesophageal adenocarcinoma varied from 0
      (e.g. Thailand) to 0.6 (Scotland, males, 95% CI : 0.56, 0.64); for proximal
      stomach cancer from 0 (Singapore, Malay females, 95% CI : -0.01, 0.11) to 0.52
      (The Netherlands, males, 95% CI : 0.49, 0.55); and for oesophageal squamous cell
      carcinomas from 0 (non-Jews in Israel, females) to 1.84 (Brazil, Porto Alegre,
      males, 95% CI : 1.42, 2.26). There was a continuous increase in age-specific
      incidence rates with advancing age for oesophageal/proximal stomach
      adenocarcinomas, but a decrease in age-specific incidence rates for oesophageal
      squamous cell carcinoma after age 75 years. The cumulative rate trends for
      adenocarcinomas of the oesophagus and proximal stomach were often dissimilar, and
      varied by country, gender, and ethnicity. CONCLUSIONS: These results suggest that
      different risk factors may be associated with adenocarcinomas of the oesophagus
      versus the proximal stomach; the marked rate variation implies a substantial
      environmental component to the recent incidence changes.

PMID- 11821357
TI  - Commentary: Regional variations in oesophageal and gastric cardia cancers-
      implications and practice.

PMID- 11821358
TI  - Case-control study of parental age, parity and socioeconomic level in relation to
      childhood cancers.
AB  - BACKGROUND: Parental ages, parity, and social class have been found in some
      studies to be associated with particular childhood cancers. Further investigation
      is warranted because of conflicting findings, biases, and the need to test
      specific hypotheses. METHODS: A case-control study was conducted (England and
      Wales, ages 0-14 years). Cases were ascertained from the National Registry of
      Childhood Tumours, and were born and diagnosed during 1968-1986. Birth record
      controls were matched 1:1 to cases on date of birth, sex and area. Information on
      variables of interest for both groups came from birth records. In all, 10 162
      pairs could contribute to matched analyses. RESULTS: The odds ratio (OR) for
      retinoblastoma resulting from assumed new germ cell mutations among children of
      fathers aged > or =45 years was 3.0 (95% CI : 0.2-41.7). The risk of childhood
      acute lymphoblastic leukaemia (ALL) was significantly higher among children of
      older mothers and fathers, and significant trends with increasing mothers' (P <
      0.001) and fathers' (P = 0.002) ages were found. There was a strong and
      significant protective effect of increasing parity on risk of childhood ALL. The
      adjusted OR for parity of > or =5 (versus 0) was 0.5 (95% CI : 0.3-0.8). Children
      in more deprived communities had a lower risk of ALL; but this was not
      significant after confounders were allowed for. There was no significant effect
      of social class based on parental occupation on ALL risk, but the numbers were
      small in those analyses. CONCLUSIONS: The associations between ALL and parental
      ages did not disappear when children with Down syndrome were excluded, suggesting
      an additional explanation beyond known links. The strong ALL association with
      parity may be because of an unknown environmental risk factor.

PMID- 11821359
TI  - Commentary: Birth order and risk of childhood acute lymphoblastic leukaemia
      (ALL).

PMID- 11821360
TI  - Survival and sequelae of meningococcal meningitis in Ghana.
AB  - BACKGROUND: Meningococcal meningitis epidemics are frequent in the Sahel zone of
      Africa but there is little information on the frequency of long-term sequelae. We
      analysed excess mortality in the two years following the 1997 epidemic in
      northern Ghana and carried out a case-control study to assess sequelae in the
      survivors. METHODS: Two-year survival of 696 meningitis cases recorded at the War
      Memorial Hospital, Navrongo, was analysed using data from a demographic
      surveillance system. A structured questionnaire on disability and on psychiatric,
      neuropsychological and behavioural problems was administered to 505 of the
      survivors and 505 age- sex- and location-matched controls as well as to their
      respective relatives. Cases and controls underwent full neurological and
      neuropsychological examination and were evaluated for hearing impairment by
      audiometry. RESULTS: Survival rates after the first month following the attack
      were similar in cases and controls. Hearing impairment was the major sequela, and
      was reported in 6 per cent of cases and 2 per cent of controls (odds ratio [OR] =
      3.10; 95% CI : 1.48-7.09). Audiometry detected severe and profound hearing loss
      in the worse affected ear (> or =70 db) in 8/496 (1.6%) survivors but in only one
      control. Survivors of meningitis were more likely to suffer from feelings of
      tiredness (OR = 1.47; 95% CI : 1.03-2.11) and were more often reported by
      relatives to have insomnia (OR = 2.31; 95% CI : 1.17-4.82) and daily alcohol
      consumption. INTERPRETATION: Meningococcal meningitis annually causes
      approximately 10 000 cases of deafness in sub-Saharan Africa; there is a need for
      early detection of affected survivors and promotion of simple hearing devices.
      There is a sizeable burden of depressive disorders secondary to meningitis which
      should be identified and looked after appropriately.

PMID- 11821361
TI  - Commentary: Opportunities to decrease mortality and long-term sequellae
      associated with meningococcal disease in Africa.

PMID- 11821362
TI  - Sex trade involvement and rates of human immunodeficiency virus positivity among
      young gay and bisexual men.
AB  - BACKGROUND: Susceptibility to human immunodeficiency virus (HIV) infection is of
      particular concern for marginalized populations. The objective of this study was
      to determine risk factors associated with sex trade work among young gay and
      bisexual men. Further, we aimed to compare HIV prevalence and incidence among men
      involved and not involved in sex trade work. METHODS: The study is based upon
      data obtained from a prospective cohort study of young gay and bisexual men.
      Participants had completed a baseline questionnaire which elicited information on
      demographic information, sexual behaviours, and substance use. Sex trade
      involvement was defined as the exchange of money, drugs, goods, clothing, shelter
      or protection for sex within the one year prior to enrollment. Contingency table
      and multivariate logistic regression analyses were used to identify risk factors
      associated with involvement in the sex trade. RESULTS: Of the 761 eligible
      participants, 126 (16%) reported involvement in sex trade work. Multivariate
      logistic regression analysis revealed regular alcohol use (Odds Ratio [OR] = 3.6,
      95% CI : 1.8-7.2), aboriginal ethnicity (OR = 3.7, 95% CI : 1.6-8.7),
      unemployment (OR = 3.9, 95% CI : 2.1-7.3), history of residence in a psychiatric
      ward (OR = 4.2, 95% CI : 1.8-9.8), bisexual activity (OR = 7.0, 95% CI : 3.5
      14.1) and the use of crack (OR = 7.4, 95% CI : 3.0-18.7) to be independently
      associated with sex trade work. Sex trade workers had a significantly higher HIV
      prevalence at baseline compared with non-sex trade workers (7.3% versus 1.1%, P <
      0.001). As well, HIV incidence was found to be significantly higher for sex trade
      workers compared with non-sex trade workers (4.7% versus 0.9%, P = 0.011).
      CONCLUSION: Our study reveals that for male sex trade workers in this setting
      increased vulnerability to HIV infection is related to unfavourable living
      conditions, substance use and sexual risk behaviour.

PMID- 11821364
TI  - Early childhood diarrhoea and helminthiases associate with long-term linear
      growth faltering.
AB  - BACKGROUND: Although the acute mortality from diarrhoeal diseases is well
      recognized, the potentially prolonged impact of early childhood diarrhoea on
      background growth and development is often overlooked. To examine the magnitude
      and duration of the association of early childhood enteric infections with growth
      faltering in later childhood, we investigated associations of early childhood
      diarrhoea (0-2 years) and intestinal helminthiases with nutritional status from
      age 2 to 7 years. METHODS: Twice-weekly diarrhoea surveillance and quarterly
      anthropometrics were followed from 1989 to 1998 in 119 children born into a
      Northeast Brazilian shantytown. RESULTS: Diarrhoea burdens at 0-2 years old were
      significantly associated with growth faltering at ages 2-7 years, even after
      controlling for nutritional status in infancy, helminthiases at 0-2 years old,
      family income, and maternal education by Pearson correlation, multivariate linear
      regression, and repeat measures analysis. The average 9.1 diarrhoeal episodes
      before age 2 years was associated with a 3.6 cm (95% CI : 0.6-6.6 cm) growth
      shortfall at age 7 years. Early childhood helminthiasis was also associated with
      linear growth faltering and a further 4.6 cm shortfall (95% CI : 0.8-7.9 cm) at
      age 7 years. CONCLUSIONS: Early childhood diarrhoea and helminthiases
      independently associate with substantial linear growth shortfalls that continue
      beyond age 6 years. Targeted interventions for their control may have profound
      and lasting growth benefits for children in similar settings.

PMID- 11821365
TI  - Serum bilirubin concentration in a Belgian population: the association with
      smoking status and type of cigarettes.
AB  - BACKGROUND: The endogenous antioxidant serum bilirubin may scavenge free radical
      species from cigarette smoke. Smokers are expected to have lower serum bilirubin
      levels than never smokers, but this has never been evaluated in a random
      population sample of women and men. In addition, in vitro studies indicate that
      filter cigarette smoke might enhance bilirubin oxidation more than non-filter
      cigarette smoke. METHODS: In this paper, data were analysed from the Belgian
      Interuniversity Research on Nutrition and Health (BIRNH) study. We investigated
      the association of smoking and type of cigarettes with serum bilirubin
      concentrations in men and women using multiple regression models taking into
      account differences in baseline and smoking characteristics. RESULTS: In men,
      current smokers had lower crude and adjusted serum bilirubin concentrations
      compared with never smokers (P = 0.0001). For women, the association between
      smoking and serum bilirubin concentrations adjusted for age was in the same
      direction as for men, but did not reach statistical significance. Male former
      smokers had serum bilirubin concentrations in between those of current smokers
      and never smokers, while female former smokers had even higher (+ 0.50
      micromol/l) serum bilirubin concentrations than never smokers. Male subjects
      smoking filter cigarettes showed a higher serum bilirubin concentration than
      those smoking cigarettes without a filter (adjusted difference: 0.49 micromol/l;
      P = 0.03). The duration of smoking was inversely and significantly related to
      serum bilirubin concentrations (P = 0.0003). CONCLUSION: Smoking may lower serum
      bilirubin concentrations in men, especially in those smoking non-filter
      cigarettes. The duration of smoking is a more important determinant for serum
      bilirubin concentrations than the number of cigarettes smoked per day, which may
      indicate the cumulative negative effects of smoking on the endogenous antioxidant
      system. Results for females pointed in the same direction, but were less clear,
      possibly due to low numbers of smoking women, who were largely young and smoked
      mainly filter cigarettes for a shorter period of time.

PMID- 11821366
TI  - Risk factor associations with wheezing patterns in children followed
      longitudinally from birth to 3(1/2) years.
AB  - BACKGROUND: There is a paucity of detailed longitudinal data on wheeze in early
      childhood. Not all children who wheeze in early infancy will continue to wheeze
      into childhood and beyond. This study aims to investigate possible risk factors
      for different patterns of wheeze in the pre-school years. SUBJECTS AND METHODS:
      Study participants were part of the Avon Longitudinal Study of Parents and
      Children (ALSPAC). Maternal reports of child wheeze between birth and 6 months
      and again between 30 and 42 months were gathered prospectively. Children were
      categorized into early wheeze, persistent wheeze or late onset wheeze. A large
      number of risk factors were assessed for each wheezing phenotype using
      multivariable logistic regression models. RESULTS: Over 70% of children who
      wheezed in the first 6 months did not wheeze 3 years later. Wheezing between 0-6
      months was independently associated with the presence of older siblings, male
      sex, delivery between April and December, bottle feeding, young maternal age,
      prenatal tobacco smoke exposure, atopy and parental history of asthma. From
      within this group of early wheezers, risk factors for wheeze that persisted
      beyond 6 months included pre-term delivery, young maternal age, living in rented
      local authority housing, atopy and a maternal (not paternal) history of asthma.
      Atopy and a family history of asthma emerged as the main predictors of wheeze
      that developed after 6 months of age. CONCLUSION: It is clear that a number of
      wheezing syndromes exist by 3(1/2) years, albeit with some degree of overlap.
      Detailed follow-up of this cohort is underway to determine whether risk factor
      associations determined in the first 3(1/2) years have long-term significance for
      the clinical entity termed 'asthma'.

PMID- 11821367
TI  - Pragmatic randomized trial of home visits by a nurse to elderly people with
      hypertension in Mexico.
AB  - BACKGROUND: In Mexico, hypertension is a major cause of disability and death in
      the elderly, but the most effective way to promote behaviour change in old people
      is unknown. Low resource interventions that are effective in normal healthcare
      settings are urgently needed. We report the results of a randomized trial of
      nurse-provided health and lifestyle advice during home visits to elderly people
      with hypertension in Mexico City. METHODS: Subjects were 718 people with
      hypertension aged > or =60 years, who were residents of Mexico City and were
      registered with the Family Medicine Clinics of the Mexican Institute of Social
      Security (IMSS). A randomized controlled trial was carried out in which the
      intervention group was offered nurse visits over 6 months with blood pressure
      checks and negotiated lifestyle changes. The control group continued to receive
      usual care. RESULTS: After 6 months, 36.5% of the intervention versus 6.8% of the
      control group had a blood pressure of <160/90 mmHg. The difference in the mean
      change in systolic blood pressure was 3.31 mmHg (P = 0.03, 95% CI : 6.32, 0.29)
      and the same difference in diastolic blood pressure was 3.67 mmHg (P = 0.00, 95%
      CI : 5.22, 2.12). Weight and sodium excretion fell more in the intervention
      group, but the difference was not significant. CONCLUSIONS: Nurse home visits are
      effective in reducing blood pressure in hypertensive patients aged > or =60
      years.

PMID- 11821368
TI  - Commentary: Disentangling the black box of disability prevention in older people.

PMID- 11821369
TI  - Coronary heart disease and stroke in developing countries: time to act.

PMID- 11821370
TI  - Developing effective and affordable models for non-communicable disease
      prevention and control.

PMID- 11821373
TI  - Childhood cancers and the viral hypothesis.

PMID- 11821375
TI  - Gay life expectancy revisited.

PMID- 11821376
TI  - AIDS and poverty threaten to reverse health gains in Latin America and the
      Caribbean.

PMID- 11821378
TI  - Binding of inositol hexakisphosphate (IP6) to Ku but not to DNA-PKcs.
AB  - The nonhomologous DNA end joining (NHEJ) pathway is responsible for repairing a
      major fraction of double strand DNA breaks in somatic cells of all multicellular
      eukaryotes. As an indispensable protein in the NHEJ pathway, Ku has been
      hypothesized to be the first protein to bind at the DNA ends generated at a
      double strand break being repaired by this pathway. When bound to a DNA end, Ku
      improves the affinity of another DNA end-binding protein, DNA-PK(cs), to that
      end. The Ku.DNA-PK(cs) complex is often termed the DNA-PK holoenzyme. It was
      recently shown that myo-inositol hexakisphosphate (IP(6)) stimulates the joining
      of complementary DNA ends in a cell free system. Moreover, the binding data
      suggested that IP(6) bound to DNA-PK(cs) (not to Ku). Here we clearly show that,
      in fact, IP(6) associates not with DNA-PK(cs), but rather with Ku. Furthermore,
      the binding of DNA ends and IP(6) to Ku are independent of each other. The
      possible relationship between inositol phosphate metabolism and DNA repair is
      discussed in light of these findings.

PMID- 11821379
TI  - Inhibition of histone deacetylases alters allelic chromatin conformation at the
      imprinted U2af1-rs1 locus in mouse embryonic stem cells.
AB  - Most loci that are regulated by genomic imprinting have differentially methylated
      regions (DMRs). Previously, we showed that the DMRs of the mouse Snrpn and U2af1
      rs1 genes have paternal allele-specific patterns of acetylation on histones H3
      and H4. To investigate the maintenance of acetylation at these DMRs, we performed
      chromatin immunoprecipitation on trichostatin-A (TSA)-treated and control cells.
      In embryonic stem (ES) cells and fibroblasts, brief (6-h) TSA treatment induces
      global hyperacetylation of H3 and H4. In ES cells only, TSA led to a selective
      increase in maternal acetylation at U2af1-rs1, at lysine 5 of H4 and at lysine 14
      of H3. TSA treatment of ES cells did not affect DNA methylation or expression of
      U2af1-rs1, but was sufficient to increase DNase I sensitivity along the maternal
      allele to a level comparable with that of the paternal allele. In fibroblasts,
      TSA did not alter U2af1-rs1 acetylation, and the parental alleles retained their
      differential DNase I sensitivity. At Snrpn, no changes in acetylation were
      observed in the TSA-treated cells. Our data suggest that the mechanisms
      regulating histone acetylation at DMRs are locus and developmental stage-specific
      and are distinct from those effecting global levels of acetylation. Furthermore,
      it seems that the allelic U2af1-rs1 acetylation determines DNase I
      sensitivity/chromatin conformation.

PMID- 11821380
TI  - Plunc, a member of the secretory gland protein family, is up-regulated in nasal
      respiratory epithelium after olfactory bulbectomy.
AB  - Subtraction suppression hybridization was used with high throughput screening to
      identify transcripts of genes that are differentially expressed in nasal
      epithelium following lesioning of the olfactory bulb, termed bulbectomy. We
      isolated the rat homologue of plunc, a murine gene highly expressed in lung and
      nasopharyngeal regions, by this method. Rat plunc encodes a 270-amino acid
      protein containing a putative signal peptide. plunc up-regulation in respiratory
      epithelium was confirmed by Northern blot and in situ hybridization. plunc mRNA
      was expressed in nasal epithelium, heart, lung, thymus, and salivary gland in
      adult rodent. plunc was expressed in nasal epithelium, thymus, and salivary gland
      during embryogenesis. Antibodies against Plunc detected a 31-kDa protein in lung,
      heart, and spleen. Rat nasal epithelium displayed robust immunoreactivity that
      was highly localized to the microvilli layer of respiratory epithelium. The
      expression of plunc was up-regulated after bulbectomy in respiratory epithelium.
      We also detected secreted plunc in rat and human mucus. Sequence and homology
      analyses suggest that Plunc is a member of the secretory gland protein family
      with putative bactericidal/bacteriostatic function. This is the first protein
      found in respiratory epithelium whose expression is regulated by olfactory
      neuronal injury and may provide protection against infection subsequent to
      injury.

PMID- 11821381
TI  - Preferential methylation of unmethylated DNA by Mammalian de novo DNA
      methyltransferase Dnmt3a.
AB  - DNA methylation is an epigenetic modification of DNA. There are currently three
      catalytically active mammalian DNA methyltransferases, DNMT1, -3a, and -3b. DNMT1
      has been shown to have a preference for hemimethylated DNA and has therefore been
      termed the maintenance methyltransferase. Although previous studies on DNMT3a and
      -3b revealed that they act as functional enzymes during development, there is
      little biochemical evidence about how new methylation patterns are established
      and maintained. To study this mechanism we have cloned and expressed Dnmt3a using
      a baculovirus expression system. The substrate specificity of Dnmt3a and
      molecular mechanism of its methylation reaction were then analyzed using a novel
      and highly reproducible assay. We report here that Dnmt3a is a true de novo
      methyltransferase that prefers unmethylated DNA substrates more than 3-fold to
      hemimethylated DNA. Furthermore, Dnmt3a binds DNA nonspecifically, regardless of
      the presence of CpG dinucleotides in the DNA substrate. Kinetic analysis supports
      an Ordered Bi Bi mechanism for Dnmt3a, where DNA binds first, followed by S
      adenosyl-l-methionine.

PMID- 11821382
TI  - Functional diversity of Xenopus lymphoid enhancer factor/T-cell factor
      transcription factors relies on combinations of activating and repressing
      elements.
AB  - Lymphoid enhancer factor/T-cell factor (LEF/TCF) high mobility group box
      transcription factors are the nuclear transducers of the Wnt/beta-catenin
      signaling cascade. In Xenopus, three members of the LEF/TCF family, XLEF-1, XTCF
      3, and XTCF-4, with distinct but partially overlapping expression patterns have
      been identified. The individual Xenopus LEF/TCF family members differ extremely
      in their properties of target gene regulation. We observed that in contrast to
      LEF-1, neither XTCF-3 nor XTCF-4 can induce secondary axis formation upon ventral
      overexpression in Xenopus embryos. To identify functional motifs within the
      LEF/TCF transcription factors responsible for target gene activation or
      repression, we created various mutants and a set of XLEF-1/XTCF-3 chimeras. In
      overexpression studies, we asked whether these constructs can mimic an activated
      Wnt/beta-catenin pathway and lead to the formation of a secondary body axis. In
      addition, we examined their capacity to rescue a loss-of-function phenotype given
      by dominant negative LEF-1 expression. We further analyzed their ability to
      directly activate target genes in reporter gene assays using the LEF/TCF target
      promoters, siamois and fibronectin. We found that a region homologous to exon IVa
      of human TCF-1 is an activating element. This is flanked by two small repressing
      motifs, LVPQ and SXXSS. Our findings implicate that the motifs identified here
      play an essential role in determining cell type-specific activity of LEF/TCF
      transcription factors.

PMID- 11821383
TI  - CARD-8 protein, a new CARD family member that regulates caspase-1 activation and
      apoptosis.
AB  - Caspase-associated recruitment domains (CARD) are protein-protein interaction
      modules found extensively in proteins that play important roles in apoptosis,
      NFkappaB activation, and cytokine regulation. In this study we identified a novel
      human protein, CARD-8, which contains a C-terminal CARD domain with high
      similarity to the CARD domain of caspase-1/ICE. We demonstrate that CARD-8
      interacts physically with caspase-1 and negatively regulates caspase-1-dependent
      IL-1beta generation in the THP-1 monocytic cell line. CARD-8 binds also to
      ICEBERG and pseudo-ICE, two other recently identified proteins, which bind to the
      CARD domain of caspase-1 and negatively regulate its activity. Reverse
      transcriptase-PCR analysis revealed that CARD-8 is expressed mainly in monocytes,
      placenta, lymph nodes, and spleen. This pattern of expression is consistent with
      caspase-1 expression in the same cells and tissues. CARD-8 was also found to
      negatively regulate NF-kappaB activation by TNF-alpha stimulation and by
      ectopically expressed RICK, suggesting that this protein may control cell
      survival. Consistent with these results, stable expression of CARD-8 in U937 or
      THP-1 cells sensitizes the cells to differentiation-induced apoptosis.
      Overexpression of CARD-8 can also induce apoptosis in transfected cells. The
      results suggest that CARD-8 represents a new signaling molecule involved in the
      regulation of caspase-1 and NF-kappaB activation.

PMID- 11821385
TI  - Involvement of a nine-residue loop of streptokinase in the generation of
      macromolecular substrate specificity by the activator complex through interaction
      with substrate kringle domains.
AB  - The selective deletion of a discrete surface-exposed epitope (residues 254-262;
      250-loop) in the beta domain of streptokinase (SK) significantly decreased the
      rates of substrate human plasminogen (HPG) activation by the mutant (SK(del254
      262)). A kinetic analysis of SK(del254-262) revealed that its low HPG activator
      activity arose from a 5-6-fold increase in K(m) for HPG as substrate, with little
      alteration in k(cat) rates. This increase in the K(m) for the macromolecular
      substrate was proportional to a similar decrease in the binding affinity for
      substrate HPG as observed in a new resonant mirror-based assay for the real-time
      kinetic analysis of the docking of substrate HPG onto preformed binary complex.
      In contrast, studies on the interaction of the two proteins with microplasminogen
      showed no difference between the rates of activation of microplasminogen under
      conditions where HPG was activated differentially by nSK and SK(del254-262). The
      involvement of kringles was further indicated by a hypersusceptibility of the
      SK(del254-262).plasmin activator complex to epsilon-aminocaproic acid-mediated
      inhibition of substrate HPG activation in comparison with that of the nSK.plasmin
      activator complex. Further, ternary binding experiments on the resonant mirror
      showed that the binding affinity of kringles 1-5 of HPG to SK(del254-262).HPG was
      reduced by about 3-fold in comparison with that of nSK.HPG . Overall, these
      observations identify the 250 loop in the beta domain of SK as an important
      structural determinant of the inordinately stringent substrate specificity of the
      SK.HPG activator complex and demonstrate that it promotes the binding of
      substrate HPG to the activator via the kringle(s) during the HPG activation
      process.

PMID- 11821384
TI  - Transcriptional regulation of Kaposi's sarcoma-associated herpesvirus-encoded
      oncogene viral interferon regulatory factor by a novel transcriptional silencer,
      Tis.
AB  - Viral interferon regulatory factor (vIRF) encoded by Kaposi's sarcoma-associated
      herpesvirus (KSHV) has been shown to transform NIH3T3 and Rat-1 cells, inhibit
      interferon signal transduction, and regulate the expression of KSHV genes. We had
      previously characterized the vIRF core promoter and defined a 12-O
      tetradecanoylphorbol-13-acetate (TPA)-responsive region in the upstream
      regulatory sequence of vIRF gene. Here, we have further identified a novel
      transcriptional silencer, named Tis in this region. Tis represses the promoter
      activities of vIRF and heterologous herpes simplex virus thymidine kinase genes
      in both position- and orientation-independent manners. Deletion analysis has
      identified a cis-element of 23 nucleotides that is essential for the negative
      regulation. Two Tis-binding protein complexes, named vR1 and vR2, were observed
      by electrophoretic mobility shift assays using nuclear extracts from both KSHV
      negative and -positive cell lines. A sequence fragment GAGTTAATAGGTAGAG in the
      cis-element was shown to be required for the DNA-protein interactions as well as
      the repression of vIRF promoter activity. Point-mutation analysis identified
      TTAAT and GTTAATAG as the core sequence motifs for the binding of vR1 and vR2,
      respectively. These results define the function of a novel transcriptional
      silencer in the regulation of vIRF gene expression.

PMID- 11821386
TI  - Inhibitory activity of a heterochromatin-associated serpin (MENT) against papain
      like cysteine proteinases affects chromatin structure and blocks cell
      proliferation.
AB  - MENT (Myeloid and Erythroid Nuclear Termination stage-specific protein) is a
      developmentally regulated chromosomal serpin that condenses chromatin in
      terminally differentiated avian blood cells. We show that MENT is an effective
      inhibitor of the papain-like cysteine proteinases cathepsins L and V. In
      addition, ectopic expression of MENT in mammalian cells is apparently sufficient
      to inhibit a nuclear papain-like cysteine proteinase and prevent degradation of
      the retinoblastoma protein, a major regulator of cell proliferation. MENT also
      accumulates in the nucleus, causes a strong block in proliferation, and promotes
      condensation of chromatin. Variants of MENT with mutations or deletions within
      the M-loop, which contains a nuclear localization signal and an AT-hook motif,
      reveal that this region mediates nuclear transport and morphological changes
      associated with chromatin condensation. Non-inhibitory mutants of MENT were
      constructed to determine whether its inhibitory activity has a role in blocking
      proliferation. These mutations changed the mode of association with chromatin and
      relieved the block in proliferation, without preventing transport to the nucleus.
      We conclude that the repressive effect of MENT on chromatin is mediated by its
      direct interaction with a nuclear protein that has a papain-like cysteine
      proteinase active site.

PMID- 11821387
TI  - Mitochondrial metabolism sets the maximal limit of fuel-stimulated insulin
      secretion in a model pancreatic beta cell: a survey of four fuel secretagogues.
AB  - The precise metabolic steps that couple glucose catabolism to insulin secretion
      in the pancreatic beta cell are incompletely understood. ATP generated from
      glycolytic metabolism in the cytosol, from mitochondrial metabolism, and/or from
      the hydrogen shuttles operating between cytosolic and mitochondrial compartments
      has been implicated as an important coupling factor. To identify the importance
      of each of these metabolic pathways, we have compared the fates of four fuel
      secretagogues (glucose, pyruvate, dihydroxyacetone, and glycerol) in the INS1-E
      beta cell line. Two of these fuels, dihydroxyacetone and glycerol, are normally
      ineffective as secretagogues but are enabled by adenovirus-mediated expression of
      glycerol kinase. Comparison of these two particular fuels allows the effect of
      redox state on insulin secretion to be evaluated since the phosphorylated
      products dihydroxyacetone phosphate and glycerol phosphate lie on opposite sides
      of the NADH-consuming glycerophosphate dehydrogenase reaction. Based upon
      measurements of glycolytic metabolites, mitochondrial oxidation, mitochondrial
      matrix calcium, and mitochondrial membrane potential, we find that insulin
      secretion most tightly correlates with mitochondrial metabolism for each of the
      four fuels. In the case of glucose stimulation, the high control strength of
      glucose phosphorylation sets the pace of glucose metabolism and thus the rate of
      insulin secretion. However, bypassing this reaction with pyruvate,
      dihydroxyacetone, or glycerol uncovers constraints imposed by mitochondrial
      metabolism, each of which attains a similar maximal limit of insulin secretion.
      More specifically, we found that the hyperpolarization of the mitochondrial
      membrane, related to the proton export from the mitochondrial matrix, correlates
      well with insulin secretion. Based on these findings, we propose that fuel
      stimulated secretion is in fact limited by the inherent thermodynamic constraints
      of proton gradient formation.

PMID- 11821388
TI  - Apoptotic effect of sphingosine 1-phosphate and increased sphingosine 1-phosphate
      hydrolysis on mesangial cells cultured at low cell density.
AB  - The lipid mediator sphingosine 1-phosphate (S1P) may alter the proliferation of
      mesangial cells during pathophysiological processes. Here, S1P stimulated
      proliferation of rat mesangial cells and phosphorylation of MAPKs at subconfluent
      cell density. Both effects were inhibited by pertussis toxin treatment. Mesangial
      cells expressed several S1P receptors of the endothelial differentiation gene
      family: EDG-1, -3, -5, and -8. Conversely, S1P induced apoptosis at low cell
      density (2 x 10(4) cells/cm(2)), which was demonstrated by flow cytometry and
      Hoechst staining. Apoptosis was observed also in quiescent or growing cells and
      was not reverted by lysophosphatidic acid or platelet-derived growth factor. S1P
      enhanced phosphorylation of SAPKs. Incubation with [(33)P]S1P, [(3)H]S1P, and
      [(3)H]sphingosine demonstrated increased S1P hydrolysis, resulting in enhanced
      intracellular sphingosine levels and decreased S1P levels. A rise in total
      ceramide levels was also observed; however, ceramide did not originate from
      [(3)H]sphingosine, and S1P-induced apoptosis was not inhibited by fumonisin B,
      precluding involvement of de novo ceramide synthesis in apoptosis. Therefore, we
      suggest that sphingosine accumulation and decreased S1P are primarily responsible
      for S1P-induced apoptosis. In conclusion, incubation of low-density mesangial
      cells with S1P results in apoptosis, presumably due to increased S1P hydrolysis.

PMID- 11821389
TI  - Auto-ADP-ribosylation of Pseudomonas aeruginosa ExoS.
AB  - Pseudomonas aeruginosa Exoenzyme S (ExoS) is a bifunctional type-III cytotoxin.
      The N terminus possesses a Rho GTPase-activating protein (GAP) activity, whereas
      the C terminus comprises an ADP-ribosyltransferase domain. We investigated
      whether the ADP-ribosyltransferase activity of ExoS influences its GAP activity.
      Although the ADP-ribosyltransferase activity of ExoS is dependent upon FAS, a 14
      3-3 family protein, factor-activating ExoS (FAS) had no influence on the activity
      of the GAP domain of ExoS (ExoS-GAP). In the presence of NAD and FAS, the GAP
      activity of full-length ExoS was reduced about 10-fold, whereas NAD and FAS did
      not affect the activity of the ExoS-GAP fragment. Using [(32)P]NAD, ExoS-GAP was
      identified as a substrate of the ADP-ribosyltransferase activity of ExoS. Site
      directed mutagenesis revealed that auto-ADP-ribosylation of Arg-146 of ExoS was
      crucial for inhibition of GAP activity in vitro. To reveal the auto-ADP
      ribosylation of ExoS in intact cells, tetanolysin was used to produce pores in
      the plasma membrane of Chinese hamster ovary (CHO) cells to allow the
      intracellular entry of [(32)P]NAD, the substrate for ADP-ribosylation. After a 3
      h infection of CHO cells with Pseudomonas aeruginosa, proteins of 50 and 25 kDa
      were preferentially ADP-ribosylated. The 50-kDa protein was determined to be auto
      ADP-ribosylated ExoS, whereas the 25-kDa protein appeared to represent a group of
      proteins that included Ras.

PMID- 11821390
TI  - Cloning and functional characterization of related TC10 isoforms, a subfamily of
      Rho proteins involved in insulin-stimulated glucose transport.
AB  - Insulin stimulates glucose transport via phosphatidylinositol 3-kinase-dependent
      and -independent pathways. The phosphatidylinositol 3-kinase-independent pathway
      involves activation of the G protein TC10. A cDNA encoding the mouse homolog of
      TC10 was cloned, and its gene was mapped at the distal end of chromosome 17.
      Additionally, a second gene was discovered with approximately 70% sequence
      identity to TC10. We refer to this gene as TC10beta. Both isoforms of TC10 were
      activated by insulin upon transfection in 3T3L1 adipocytes. Cotransfection of
      cells with TC10alpha or beta plus a dominant negative form of the c-cbl
      associated protein CAP prevented the activation by insulin, implicating the
      CAP/Cbl pathway. Interestingly, both forms of TC10 were also localized in lipid
      raft fractions in transfected adipocytes. However, although overexpression of
      TC10alpha completely blocked glucose transport, TC10beta only partially inhibited
      this process. Furthermore, TC10alpha overexpression disrupted adipocyte cortical
      actin, whereas TC10beta had little if any effect. Thus, there are two isoforms of
      this key signaling intermediate, both of which are activated by insulin, but they
      may play different roles in initiating downstream effectors that influence
      glucose transport.

PMID- 11821391
TI  - Role of 3-phosphoinositides in the maturation of Salmonella-containing vacuoles
      within host cells.
AB  - Salmonella typhimurium invades mammalian cells and replicates within a vacuole
      that protects it from the host's microbicidal weapons. The Salmonella-containing
      vacuole (SCV) undergoes a remodelling akin to that of the host cell's endocytic
      pathway, but SCV progression is arrested prior to fusion with lysosomes. We
      studied the role of phosphatidylinositol 3-kinase (PI3-K) in SCV maturation
      within HeLa cells. Phosphatidylinositol 3-phosphate (PI3P), monitored in situ
      using fluorescent conjugates of FYVE or PX domains, was found to accumulate
      transiently on the SCV. Wortmannin prevented PI3P accumulation and the
      recruitment of EEA1 but did not affect the association of Rab5 with the SCV.
      Importantly, inhibition of PI3-K also impaired fusion of the SCV with vesicles
      containing LAMP-1. Rab7, which is thought to be required for association of LAMP
      1 with the SCV, still associated with SCV in wortmannin-treated cells. We have
      therefore concluded that a 3-phosphoinositide-dependent step exists following
      recruitment of Rab7 to the SCV. The data also imply that 3-phosphoinositide
      dependent effectors of Rab5 are not an absolute requirement for recruitment of
      Rab7. Despite failure to acquire LAMP-1, the SCV persists and allows effective
      replication of Salmonella within wortmannin-treated host cells. These findings
      imply that PI3-K is involved in the development of the SCV but is not essential
      for intracellular survival and proliferation of Salmonella.

PMID- 11821393
TI  - Crystal structure of imaginal disc growth factor-2. A member of a new family of
      growth-promoting glycoproteins from Drosophila melanogaster.
AB  - Imaginal disc growth factor-2 (IDGF-2) is a member of a recently described family
      of Drosophila melanogaster-soluble polypeptide growth factors that promote cell
      proliferation in imaginal discs. Although their precise mode of action has not
      been established, IDGFs cooperate with insulin in stimulating the growth of
      imaginal disc cells. We report the crystal structure of IDGF-2 at 1.3-A
      resolution. The structure shows the classical (betaalpha)(8) barrel-fold of
      family 18 glycosyl hydrolases, with an insertion of an alpha + beta domain
      similar to that of Serratia marcescens chitinases A and B. However, amino acid
      substitutions in the consensus catalytic sequence of chitinases give IDGF-2 a
      less negatively charged environment in its putative ligand-binding site and
      preclude the nucleophilic attack mechanism of chitin hydrolysis. Particularly
      important is the replacement of Glu by Gln at position 132, which has been shown
      to abolish enzymatic activity in chitinases. Nevertheless, a modest conservation
      of residues that participate in oligosaccharide recognition suggests that IDGF-2
      could bind carbohydrates, assuming several conformational changes to open the
      partially occluded binding site. Thus, IDGFs may have evolved from chitinases to
      acquire new functions as growth factors, interacting with cell surface
      glycoproteins implicated in growth-promoting processes, such as the Drosophila
      insulin receptor.

PMID- 11821392
TI  - alpha-Synuclein interacts with phospholipase D isozymes and inhibits pervanadate
      induced phospholipase D activation in human embryonic kidney-293 cells.
AB  - alpha-Synuclein has been implicated in the pathogenesis of many neurodegenerative
      diseases, including Parkinson's disease and Alzheimer's disease. Although the
      function of alpha-synuclein remains largely unknown, recent studies have
      demonstrated that this protein can interact with phospholipids. To address the
      role of alpha-synuclein in neurodegenerative disease, we have investigated
      whether it binds phospholipase D (PLD) and affects PLD activity in human
      embryonic kidney (HEK)-293 cells overexpressing wild type alpha-synuclein or the
      mutant forms of alpha-synuclein (A53T, A30P) associated with Parkinson's disease.
      Tyrosine phosphorylation of alpha-synuclein appears to play a modulatory role in
      the inhibition of PLD, because mutation of Tyr(125) to Phe slightly increases
      inhibitory effect of alpha-synuclein on PLD activity. Treatment with pervanadate
      or phorbol myristate acetate inhibits PLD more in HEK 293 cells overexpressing
      alpha-synuclein than in control cells. Binding of alpha-synuclein to PLD requires
      phox and pleckstrin homology domain of PLD and the amphipathic repeat region and
      non-Abeta component of alpha-synuclein. Although biologically important, co
      transfection studies indicate that the interaction of alpha-synuclein with PLD
      does not influence the tendency of alpha-synuclein to form pathological
      inclusions. These results suggest that the association of alpha-synuclein with
      PLD, and modulation of PLD activity, is biologically important, but PLD does not
      appear to play an essential role in the pathophysiology of alpha-synuclein.

PMID- 11821394
TI  - The atrial natriuretic peptide receptor (NPR-A/GC-A) is dephosphorylated by
      distinct microcystin-sensitive and magnesium-dependent protein phosphatases.
AB  - Natriuretic peptide receptor (NPR)-A is the primary signaling receptor for atrial
      natriuretic peptide and brain natriuretic peptide. Ligand binding to NPR-A
      rapidly activates its guanylyl cyclase domain, but its rate of cGMP synthesis
      declines with time. This waning of activity is called homologous desensitization
      and is mediated in part by receptor dephosphorylation. Here, we characterize two
      distinct NPR-A phosphatase activities. The serine/threonine protein phosphatase
      inhibitor, microcystin, inhibited the desensitization of NPR-A in membrane
      guanylyl cyclase assays in the absence of magnesium. EDTA also inhibited the
      desensitization, whereas MgCl(2) stimulated the desensitization. Because the
      effects of microcystin and EDTA were additive, and microcystin did not block the
      magnesium-dependent desensitization, the targets for these agents appear to be
      distinct. Incubation of membranes at 37 degrees C stimulated the
      dephosphorylation of NPR-A, and microcystin blocked the temperature-dependent
      dephosphorylation. The addition of MgCl(2) or MnCl(2), but not CaCl(2), further
      stimulated the dephosphorylation of NPR-A, and microcystin failed to inhibit this
      process. The desensitization required changes in the phosphorylation state of NPR
      A because the guanylyl cyclase activity of a receptor variant containing
      glutamate substitutions at all six phosphorylation sites was unaffected by
      MgCl(2), EDTA, or microcystin. Together, these data indicate that NPR-A is
      regulated by two distinct phosphatases, possibly including a member of the
      protein phosphatase 2C family. Finally, we observed that the desensitization of
      NPR-A in membranes from mouse kidneys and NIH3T3 cells was increased by prior
      exposure to atrial natriuretic peptide, suggesting that hormone binding enhances
      receptor dephosphorylation.

PMID- 11821395
TI  - The luminal domain of ATF6 senses endoplasmic reticulum (ER) stress and causes
      translocation of ATF6 from the ER to the Golgi.
AB  - ATF6 is an endoplasmic reticulum (ER) transmembrane transcription factor that is
      activated by the ER stress/unfolded protein response by cleavage of its N
      terminal half from the membrane. We find that ER stress induces ATF6 to move from
      the ER to the Golgi, where it is cut in its luminal domain by site 1 protease.
      ATF6 contains a single transmembrane domain with 272 amino acids oriented in the
      lumen of the ER. We found that this luminal domain is required for the
      translocation of ATF6 to the Golgi and its subsequent cleavage, and we have
      mapped regions required for these properties. These results suggest that the
      conserved CD1 region is required for translocation, whereas the CD2 region is
      required for site 1 protease cleavage. We also find that ATF6's luminal domain is
      sufficient to sense ER stress and cause translocation to the Golgi when fused to
      LZIP, another ER transmembrane protein. These results show that ATF6 has a
      mechanism to sense ER stress and respond by translocation to the Golgi.

PMID- 11821396
TI  - Macrophages inhibit Salmonella typhimurium replication through MEK/ERK kinase and
      phagocyte NADPH oxidase activities.
AB  - Host responses during the later stages of Salmonella-macrophage interactions are
      critical to controlling infection but have not been well characterized. After 24
      h of infection, nearly half of interferon-gamma-primed murine RAW 264.7
      macrophage-like cells infected by Salmonella enterica serovar Typhimurium
      contained filamentous bacteria. Bacterial filamentation indicates a defect in
      completing replication and has been previously observed in bacteria responding to
      a variety of stresses. To understand whether macrophage gene expression was
      responsible for this effect on Salmonella Typhimurium replication, we used gene
      arrays to profile interferon-gamma-primed RAW 264.7 cell gene expression
      following infection. We observed an increase in MEK1 kinase mRNA at 8 h, an
      increase in MEK protein at 24 h, and measured phosphorylation of MEK's downstream
      target kinase, ERK1/2, throughout the 24-h infection period. Treatment of cells
      with MEK kinase inhibitors significantly reduced numbers of filamentous bacteria
      observed within macrophages after 24 h and increased the number of intracellular
      colony-forming units. Phagocyte NADPH oxidase inhibitors and antioxidants also
      significantly reduced bacterial filamentation. Either MEK kinase or phagocyte
      oxidase inhibitors could be added 4-8 h after infection and still significantly
      decrease bacterial filamentation. Oxidase activity appears to mediate bacterial
      filamentation in parallel to MEK kinase signaling, while inducible nitric-oxide
      synthase inhibitors had no significant effect on bacterial morphology. In
      summary, Salmonella Typhimurium infection of interferon-gamma-primed macrophages
      triggers a MEK kinase cascade at later infection times, and both MEK kinase and
      phagocyte NADPH oxidase activity impair bacterial replication. These two
      signaling pathways mediate a host bacteriostatic pathway and may play an
      important role in innate host defense against intracellular pathogens.

PMID- 11821397
TI  - Hepatocyte growth factor/scatter factor inhibits UVB-induced apoptosis of human
      keratinocytes but not of keratinocyte-derived cell lines via the
      phosphatidylinositol 3-kinase/AKT pathway.
AB  - Acute irreparable UV-induced DNA damage leads to apoptosis of epidermal
      keratinocytes (KC) and the formation of sunburn cells, whereas less severely
      damaged cells survive but harbor the potential of tumor formation. Here we report
      that hepatocyte growth factor/scatter factor (HGF/SF) prevents UVB-induced
      apoptosis in primary KC cultured in vitro. When we analyzed the signaling
      pathways initiated by the HGF/SF receptor c-met, we found that the
      phosphatidylinositol (PI) 3-kinase and its downstream-element AKT and the mitogen
      activated protein (MAP) kinase were activated. Inhibition of PI 3-kinase led to a
      complete abrogation of the anti-apoptotic effect of HGF/SF, whereas blockade of
      the MAP kinase pathway had no effect. In contrast to the observation with primary
      KC, HGF/SF could not enhance survival after UVB irradiation of HaCaT and A431
      cell lines, despite the fact that in these cells the PI 3-kinase and MAP kinase
      pathways were also activated by HGF/SF. Cell cycle analysis of KC revealed a
      G(2)/M arrest after UVB irradiation and a complete loss of proliferating cells.
      Because HGF/SF in the skin is produced by dermal fibroblasts, our findings
      suggest that the HGF/SF-mediated rescue of KC from apoptosis represents an
      important paracrine loop by which UVB-damaged KC can be kept alive to maintain
      the epidermal barrier function but cannot further proliferate, thereby preventing
      the induction of epithelial skin tumors.

PMID- 11821398
TI  - Extracellular mRNA induces dendritic cell activation by stimulating tumor
      necrosis factor-alpha secretion and signaling through a nucleotide receptor.
AB  - We previously demonstrated that dendritic cell (DC) pulsing with antigen-encoded
      mRNA resulted in the loading of both major histocompatibility complex class I and
      II antigen presentation pathways and the delivery of an activation signal.
      Coculture of mRNA-pulsed DC with T cells led to the induction of a potent primary
      immune response. DC, in addition to recognizing foreign antigens through pattern
      recognition receptors, also must respond to altered self, transformed, or
      intracellularly infected cells. This occurs through cell surface receptors that
      recognize products of inflammation and cell death. In this report, we
      characterize two signaling pathways utilized by extracellular mRNA to activate
      DC. In addition, a novel ligand, poly(A), is identified that mediates signaling
      through a receptor that can be inhibited by pertussis toxin and suramin and can
      be desensitized by ATP and ADP, suggesting a P2Y type nucleotide receptor. The
      role of this signaling activity in vaccine design and the potential effect of
      mRNA released by damaged cells in the induction of immune responsiveness is
      discussed.

PMID- 11821399
TI  - Propionyl-coenzyme A synthase from Chloroflexus aurantiacus, a key enzyme of the
      3-hydroxypropionate cycle for autotrophic CO2 fixation.
AB  - The 3-hydroxypropionate cycle has been proposed as a new autotrophic CO(2)
      fixation pathway for the phototrophic green non-sulfur eubacterium Chloroflexus
      aurantiacus and for some chemotrophic archaebacteria. The cycle requires the
      reductive conversion of the characteristic intermediate 3-hydroxypropionate to
      propionyl-CoA. The specific activity of the 3-hydroxypropionate-, CoA-, K(+)-,
      and MgATP-dependent oxidation of NADPH in autotrophically grown cells was 0.09
      micromol min(-1) mg(-1) protein, which was 2-fold down-regulated in
      heterotrophically grown cells. Unexpectedly, a single enzyme catalyzes the entire
      reaction sequence: 3-hydroxypropionate + MgATP + CoA + NADPH + H(+) --> propionyl
      CoA + MgAMP + PP(i) + NADP(+) + H(2)O. The enzyme was purified 30-fold to near
      homogeneity and has a very large native molecular mass between 500 and 800 kDa,
      with subunits of about 185 kDa as judged by SDS-PAGE, suggesting a homotrimeric
      or homotetrameric structure. Upon incubation of this new enzyme, termed propionyl
      CoA synthase, with the proteinase trypsin, the NADPH oxidation function of the
      enzyme was lost, whereas the enzyme still activated 3-hydroxypropionate to its
      CoA-thioester and dehydrated it to acrylyl-CoA. SDS-PAGE revealed that the
      subunits of propionyl-CoA synthase had been cleaved once and the N-terminal amino
      acid sequences of the two trypsin digestion products were determined. Two parts
      of the gene encoding propionyl-CoA synthase (pcs) were identified on two contigs
      of an incomplete genome data base of C. aurantiacus, and the sequence of the pcs
      gene was completed. Propionyl-CoA synthase is a natural fusion protein of 201 kDa
      consisting of a CoA ligase, an enoyl-CoA hydratase, and an enoyl-CoA reductase,
      the reductase domain containing the trypsin cleavage site. Similar polyfunctional
      large enzymes are common in secondary metabolism (e.g. polyketide synthases) but
      rare in primary metabolism (e.g. eukaryotic type I fatty acid synthase). These
      results lend strong support to the operation of the proposed pathway in
      autotrophic CO(2) fixation.

PMID- 11821400
TI  - Expression of Sorsby's fundus dystrophy mutations in human retinal pigment
      epithelial cells reduces matrix metalloproteinase inhibition and may promote
      angiogenesis.
AB  - Sorsby's fundus dystrophy (SFD) is an autosomal dominant degenerative disease of
      the macula caused by mutations in the tissue inhibitor of metalloproteinase-3
      (TIMP-3) gene. Choroidal neovascularization is a hallmark of this disease, which
      closely resembles the exudative form of age-related macular degeneration.
      However, the mechanism by which TIMP-3 mutations induce the disease phenotype in
      SFD remains unknown. To address this question we established human retinal
      pigment epithelial cell lines expressing wild type or S156C (Ser(156) changed to
      cysteine) mutant TIMP-3. S156C TIMP-3 had reduced matrix metalloproteinase (MMP)
      inhibitory activity in retinal pigment epithelial cells and resulted in increased
      secretion and activation of gelatinase A and B. The conditioned medium from these
      cells induced angiogenesis in "in vivo" chick chorioallantoic membrane assays
      that could be reversed with recombinant wild type TIMP-3. Our data indicate that
      the choroidal neovascularization in SFD may be a result of increased MMP
      activity, which could lead to the stimulation of angiogenesis. These results also
      suggest the potential therapeutic use of TIMP-3 or synthetic MMP inhibitors in
      this disease.

PMID- 11821401
TI  - Insulin-like growth factor-binding protein 5 (IGFBP-5) interacts with a four and
      a half LIM protein 2 (FHL2).
AB  - Recent studies using insulin-like growth factor I (IGF-I) knockout mice
      demonstrate that IGF-binding protein (IGFBP)-5, an important bone formation
      regulator, itself is a growth factor with cellular effects not dependent on IGFs.
      Because IGFBP-5 contains a nuclear localization sequence that mediates transport
      of IGFBP-5 into the nucleus, we propose that IGFBP-5 interacts with nuclear
      proteins to affect transcription of genes involved in bone formation. We
      therefore undertook studies to identify proteins that bind to IGFBP-5 using IGFBP
      5 as bait in a yeast two-hybrid screen of a U2 human osteosarcoma cDNA library.
      Five related clones that interacted strongly with the bait corresponded to the
      FHL2 gene, which contains four and a half LIM domains. Co-immunoprecipitation
      studies with lysates from U2 cells overexpressing FHL2 and IGFBP-5 confirmed that
      interaction between IGFBP-5 and FHL2 occurs in whole cells. In vitro interaction
      studies revealed that purified FHL2 interacted with IGFBP-5 but not with IGFBP-3,
      -4, or -6. Northern blot analysis showed that FHL2 was strongly expressed in
      human osteoblasts. Nuclear localization of both FHL2 and IGFBP-5 was evident from
      Western immunoblot analysis and immunofluorescence. The role of FHL2 as an
      intracellular mediator of the effects of IGFBP-5 and other osteoregulatory agents
      in osteoblasts will need to be verified in future studies.

PMID- 11821402
TI  - Trichostatin A-induced detransformation correlates with decreased focal adhesion
      kinase phosphorylation at tyrosine 861 in ras-transformed fibroblasts.
AB  - To elucidate the role of focal adhesion kinase (pp125FAK) in transformation, its
      phosphorylation in transformed fibroblasts was compared with that of
      detransformed fibroblasts induced by a histone deacetylase inhibitor,
      trichostatin A (TSA). Inhibition of histone deacetylase activity in two different
      ras-transformed fibroblast lines by TSA induced a morphological change into a
      flattened and more spread morphology, implying detransformation. These
      morphological changes included increased spreading ability of transformed NIH 3T3
      cells on fibronectin. Of the six tyrosine phosphorylation sites in pp125FAK,
      phosphorylation at position 861 (Tyr-861) was clearly decreased during
      detransformation by TSA. It resulted from decreased activity of Src family
      tyrosine kinase and/or decreased amount of Src kinase interacting with pp125FAK.
      Furthermore, phosphorylation of Tyr-861 was reduced substantially by the Src
      family kinase inhibitor, PP1, while overexpression of Src kinase increased its
      phosphorylation, implying that Src kinase regulates phosphorylation of pp125FAK
      at Tyr-861. All of these findings suggest that increased phosphorylation of
      pp125FAK at Tyr-861 correlates with Ras-induced transformation of fibroblasts,
      and TSA is able to detransform them through regulation of pp125FAK
      phosphorylation at Tyr-861 by an Src family kinase.

PMID- 11821403
TI  - Deletions in the acidic lipid-binding region of the plasma membrane Ca2+ pump. A
      mutant with high affinity for Ca2+ resembling the acidic lipid-activated enzyme.
AB  - The C-terminal segment of the loop between transmembrane helices 2 and 3 (A(L)
      region) of the plasma membrane Ca(2+) pump (PMCA) is not conserved in other P
      ATPases. Part of this region, just upstream from the third transmembrane domain,
      has been associated with activation of the PMCA by acidic lipids. cDNAs coding
      for mutants of the Ca(2+) pump isoform h4xb with deletions in the A(L) region
      were constructed, and the proteins were successfully expressed in either COS or
      Chinese hamster ovary cells. Mutants with deletions in the segment 296-349 had
      full Ca(2+) transport activity, but deletions involving the segment of amino
      acids 350-356 were inactive suggesting that these residues are required for a
      functional PMCA. In the absence of calmodulin the V(max) of mutant d296-349 was
      similar to that of the recombinant wild type pump, but its K(0.5) for Ca(2+) was
      about 5-fold lower. The addition of calmodulin increased the V(max) and the
      apparent Ca(2+) affinity of both the wild type and d296-349 enzymes indicating
      that the activating effects of calmodulin were not affected by the deletion. At
      low concentrations of Ca(2+) and in the presence of saturating amounts of
      calmodulin, the addition of phosphatidic acid increased about 2-fold the activity
      of the recombinant wild type pump. In contrast, under these conditions
      phosphatidic acid did not significantly change the activity of mutant d296-349.
      Taken together these results suggest that (a) deletion of residues 296-349
      recreates a form of PMCA similar to that resulting from the binding of acidic
      lipids at the A(L) region; (b) the A(L) region acts as an acidic lipid-binding
      inhibitory domain capable of adjusting the Ca(2+) affinity of the PMCA to the
      lipid composition of the membrane; and (c) the function of the A(L) region is
      independent of the autoinhibition by the C-terminal calmodulin-binding region.

PMID- 11821404
TI  - Fe2+-catalyzed site-specific cleavage of the large subunit of ribulose 1,5
      bisphosphate carboxylase close to the active site.
AB  - Previous work has demonstrated that the large subunit (rbcL) of ribulose 1,5
      bisphosphate carboxylase/oxygenase (RuBisCo) from wheat is cleaved at Gly-329 by
      the Fe(2+)/ascorbate/H(2)O(2) system (Ishida, H., Makino, A., and Mae, T. (1999)
      J. Biol. Chem. 274, 5222-5226). In this study, we found that the rbcL could also
      be cleaved into several other fragments by increasing the incubation time or the
      Fe(2+) concentration. By combining immunoblotting with N-terminal amino acid
      sequencing, cleavage sites were identified at Gly-404, Gly-380, Gly-329, Ala-296,
      Asp-203, and Gly-122. Conformational analysis demonstrated that five of them are
      located in the alpha/beta-barrel, whereas Gly-122 is in the N-terminal domain but
      near the bound metal in the adjacent rbcL. All of these residues are at or very
      close to the active site and are just around the metal-binding site within a
      radius of 12 A. Furthermore, their C(alpha)H groups are completely or partially
      exposed to the bound metal. A radical scavenger, activation of RuBisCo, or
      binding of a reaction-intermediate analogue to the activated RuBisCo, inhibited
      the fragmentation. These results strongly suggest that the rbcL is cleaved by
      reactive oxygen species generated at the metal-binding site and that proximity
      and favorable orientation are probably the most important parameters in
      determining the cleavage sites.

PMID- 11821405
TI  - Mass spectrometric analysis of the N terminus of translational initiation factor
      eIF4G-1 reveals novel isoforms.
AB  - In eukaryotes, translation initiation factor 4G (eIF4G) acts as the central
      binding protein for an unusually large number of proteins involved in mRNA
      metabolism. Several gene products homologous to eIF4G have been described, the
      most studied being eIF4G-1. By its association with other initiation factors,
      eIF4G-1 effects mRNA cap and poly(A) recognition, unwinding of secondary
      structure, and binding to the 43S initiation complex. Multiple electrophoretic
      isoforms of eIF4G-1 are observed, and multiple cDNAs have been reported, yet the
      relationship between the two is not known. We report here a new cDNA for eIF4G-1,
      present as a previously unidentified human expressed sequence tag, that extends
      the long open reading frame, provides a new in-frame initiation codon, and
      predicts a longer form of eIF4G-1 than reported previously. eIF4G isoforms from
      human K562 cells were cleaved with recombinant Coxsackievirus 2A protease and the
      N- terminal domains purified by m(7)GTP-Sepharose chromatography and
      polyacrylamide gel electrophoresis. Proteins were digested with proteolytic
      enzymes and peptides masses determined by matrix-assisted laser desorption
      ionization-time of flight mass spectrometry. In selected cases, peptides were
      sequenced by electrospray-mass spectrometry fragmentation. This identified the N
      termini of the three most abundant eIF4G-1 isoforms, two of which had not
      previously been proposed. These proteins appear to have been initiated from three
      different AUG codons.

PMID- 11821406
TI  - Recombinant human laminin-10 (alpha5beta1gamma1). Production, purification, and
      migration-promoting activity on vascular endothelial cells.
AB  - The laminin (LN) family of large heterotrimeric extracellular matrix
      glycoproteins has multiple functions: LNs take part in the regulation of
      processes such as cell migration, differentiation, and proliferation, in addition
      to contributing to the structure of basement membranes. LN-10, composed of
      alpha5, beta1, and gamma1 chains, is widely distributed in most basement
      membranes of both epithelia and endothelia. We determined the complete human cDNA
      sequence for the LN alpha5 chain and produced recombinant human LN-10 (rLN-10) in
      HEK293 cells by triple transfection of full-length cDNAs encoding the human LN
      alpha5, beta1, and gamma1 chains. The rLN-10 was purified using affinity
      chromatography and had an apparent molecular mass of approximately 800 kDa in SDS
      PAGE and a native domain structure in rotary shadowing electron microscopy. By
      using function-blocking monoclonal antibodies, integrin alpha(3)beta(1) was found
      to be a major mediator of adhesion of HT-1080 and human saphenous vein
      endothelial cells. Human saphenous vein endothelial cells adhered more strongly
      to rLN-10 than to LN-1 and LN-8 and showed better migration on rLN-10, compared
      with several other matrices. Considering the cell adhesive and migration
      promoting properties of rLN-10 on endothelial cells, this molecule could be
      useful in improving the biocompatibility and endothelialization of vascular
      grafts.

PMID- 11821407
TI  - Repair of sequence-specific 125I-induced double-strand breaks by nonhomologous
      DNA end joining in mammalian cell-free extracts.
AB  - In mammalian cells, nonhomologous DNA end joining (NHEJ) is considered the major
      pathway of double-strand break (DSB) repair. Rejoining of DSB produced by decay
      of (125)I positioned against a specific target site in plasmid DNA via a triplex
      forming oligonucleotide (TFO) was investigated in cell-free extracts from Chinese
      hamster ovary cells. The efficiency and quality of NHEJ of the "complex" DSB
      induced by the (125)I-TFO was compared with that of "simple" DSB induced by
      restriction enzymes. We demonstrate that the extracts are indeed able to rejoin
      (125)I-TFO-induced DSB, although at approximately 10-fold decreased efficiency
      compared with restriction enzyme-induced DSB. The resulting spectrum of junctions
      is highly heterogeneous exhibiting deletions (1-30 bp), base pair substitutions,
      and insertions and reflects the heterogeneity of DSB induced by the (125)I-TFO
      within its target site. We show that NHEJ of (125)I-TFO-induced DSB is not a
      random process that solely depends on the position of the DSB but is driven by
      the availability of microhomology patches in the target sequence. The similarity
      of the junctions obtained with the ones found in vivo after (125)I-TFO-mediated
      radiodamage indicates that our in vitro system may be a useful tool to elucidate
      the mechanisms of ionizing radiation-induced mutagenesis and repair.

PMID- 11821408
TI  - Presteady-state analysis of avian sarcoma virus integrase. II. Reverse-polarity
      substrates identify preferential processing of the U3-U5 pair.
AB  - The integrase-catalyzed insertion of the retroviral genome into the host
      chromosome involves two reactions in vivo: 1) the binding and endonucleolytic
      removal of the terminal dinucleotides of the viral DNA termini and 2) the
      recombination of the ends with the host DNA. Kukolj and Skalka (Kukolj, G., and
      Skalka, A. M. (1995) Genes Dev. 9, 2556-2567) have previously shown that
      tethering of the termini enhances the endonucleolytic activities of integrase. We
      have used 5'-5' phosphoramidites to design reverse-polarity tethers that allowed
      us to examine the reactivity of two viral long terminal repeat-derived sequences
      when concurrently bound to integrase and, additionally, developed presteady-state
      assays to analyze the initial exponential phase of the reaction, which is a
      measure of the amount of productive nucleoprotein complexes formed during
      preincubation of integrase and DNA. Furthermore, the reverse-polarity tether
      circumvents the integrase-catalyzed splicing reaction (Bao, K., Skalka, A. M.,
      and Wong, I. (2002) J. Biol. Chem. 277, 12089-12098) that obscures accurate
      analysis of the reactivities of synapsed DNA substrates. Consequently, we were
      able to establish a lower limit of 0.2 s(-1) for the rate constant of the
      processing reaction. The analysis showed the physiologically relevant U3/U5 pair
      of viral ends to be the preferred substrate for integrase with the U3/U3
      combination favored over the U5/U5 pair.

PMID- 11821409
TI  - Presteady-state analysis of avian sarcoma virus integrase. I. A splicing activity
      and structure-function implications for cognate site recognition.
AB  - Integrase catalyzes insertion of a retroviral genome into the host chromosome.
      After reverse transcription, integrase binds specifically to the ends of the
      duplex retroviral DNA, endonucleolytically cleaves two nucleotides from each 3'
      end (the processing activity), and inserts these ends into the host DNA (the
      joining activity) in a concerted manner. In first-turnover experiments with
      synapsed DNA substrates, we observed a novel splicing activity that resembles an
      integrase joining reaction but uses unprocessed ends. This splicing reaction
      showed an initial exponential phase (k(splicing) = 0.02 s(-1)) of product
      formation and generated products macroscopically indistinguishable from those
      created by the processing and joining activities, thus bringing into question
      methods previously used to quantitate these reactions in a time regime where
      multiple turnovers of the enzyme have occurred. With a presteady-state assay,
      however, we were able to distinguish between different pathways that led to
      formation of identical products. Furthermore, the splicing reaction allowed
      characterization of substrate binding and specificity. Although integrase
      requires only a 3' hydroxyl with respect to nucleophiles derived from DNA, it
      specifically favors the cognate sequence CATT as the electrophile. These
      experimental results support a two-site "switching" model for binding and
      catalysis of all three integrase activities.

PMID- 11821410
TI  - Msn2p/Msn4p act as a key transcriptional activator of yeast cytoplasmic thiol
      peroxidase II.
AB  - We observed that the transcription of Saccharomyces cerevisiae cytoplasmic thiol
      peroxidase type II (cTPx II) (YDR453C) is regulated in response to various
      stresses (e.g. oxidative stress, carbon starvation, and heat-shock). It has been
      suggested that both transcription-activating proteins, Yap1p and Skn7p, regulate
      the transcription of cTPx II upon exposure to oxidative stress. However, a
      dramatic loss of transcriptional response to various stresses in yeast mutant
      strains lacking both Msn2p and Msn4p suggests that the transcription factors act
      as a principal transcriptional activator. In addition to two Yap1p response
      elements (YREs), TTACTAA and TTAGTAA, the presence of two stress response
      elements (STREs) (CCCCT) in the upstream sequence of cTPx II also suggests that
      Msn2p/Msn4p could control stress-induced expression of cTPx II. Analysis of the
      transcriptional activity of site-directed mutagenesis of the putative STREs
      (STRE1 and STRE2) and YREs (TRE1 and YRE2) in terms of the activity of a lacZ
      reporter gene under control of the cTPx II promoter indicates that STRE2 acts as
      a principal binding element essential for transactivation of the cTPx II
      promoter. The transcriptional activity of the cTPx II promoter was exponentially
      increased after postdiauxic growth. The transcriptional activity of the cTPx II
      promoter is greatly increased by rapamycin. Deletion of Tor1, Tor2, Ras1, and
      Ras2 resulted in a considerable induction when compared with their parent
      strains, suggesting that the transcription of cTPx II is under negative control
      of the Ras/cAMP and target of rapamycin signaling pathways. Taken together, these
      results suggest that cTPx II is a target of Msn2p/Msn4p transcription factors
      under negative control of the Ras-protein kinase A and target of rapamycin
      signaling pathways. Furthermore, the accumulation of cTPx II upon exposure to
      oxidative stress and during the postdiauxic shift suggests an important
      antioxidant role in stationary phase yeast cells.

PMID- 11821411
TI  - Identification of Myc-mediated death response pathways by microarray analysis.
AB  - To understand the mechanisms of Myc-mediated apoptosis induced by DNA damage, we
      have characterized the death kinetics of three Rat-1 fibroblast cell lines that
      either overexpress Myc or lack Myc and their parental wild-type cells following
      exposure to the DNA-damaging agent VP-16, and we monitored the changes in gene
      expression using microarray. We have identified three groups of genes whose
      expressions are distinctly regulated during this process. One cluster (Cluster A)
      revealed a VP-16-dependent but Myc-independent induction of a set of genes that
      is not linked to the apoptotic response. Two other gene clusters, however, were
      associated with VP-16-induced apoptosis. Cluster B, which includes p53-responsive
      genes, was associated with the temporal onset of apoptosis but accounted for only
      the basal apoptosis. However, Cluster C, which includes c-jun, was highly
      regulated by Myc and appeared to be critical to mounting the maximal apoptotic
      response in Myc-expressing cells. Furthermore, the Myc level dropped sharply
      following VP-16 exposure, which varied inversely with the induction of Cluster C
      genes, suggesting Myc normally represses their transcription. Thus, we have
      proposed that removal of Myc-mediated repression of apoptotic signals, combined
      with Myc-associated acceleration of the p53 responsive pathway, results in
      complete and rapid cell death following DNA damage.

PMID- 11821412
TI  - Mass spectrometric characterization of full-length rat selenoprotein P and three
      isoforms shortened at the C terminus. Evidence that three UGA codons in the mRNA
      open reading frame have alternative functions of specifying selenocysteine
      insertion or translation termination.
AB  - Selenoprotein P is an abundant extracellular glycoprotein. Its mRNA contains 10
      UGAs in an open reading frame terminated by a UAA. This predicts that full-length
      selenoprotein P will contain 10 selenocysteine residues. Full-length
      selenoprotein P and three smaller isoforms that have identical N termini have
      been demonstrated. Selenoprotein P was purified from rat plasma, and the four
      isoforms were separated by heparin chromatography and SDS-PAGE. Mass
      spectrometric peptide analysis of the full-length isoform verified 357 of its 366
      predicted amino acid residues, including its C terminus and all 10
      selenocysteines. The C termini of the smaller isoforms were characterized by mass
      spectrometry. The shortened isoforms terminated where the second, third, and
      seventh selenocysteine residues were predicted to be. This suggests that all
      isoforms arise from the same mRNA and that the UGAs that specify the second,
      third, and seventh selenocysteines in full-length selenoprotein P can
      alternatively serve to terminate translation, producing the shorter isoforms.

PMID- 11821413
TI  - Interaction of the molecular chaperone Hsp70 with human NAD(P)H:quinone
      oxidoreductase 1.
AB  - NAD(P)H:quinone oxidoreductase 1 (EC; DT-Diaphorase, NQO1) is predominantly a
      cytosolic flavoenzyme that catalyzes a two-electron reduction. Using human tumor
      cell lines devoid of NQO1 enzymatic activity, we have previously identified a
      single nucleotide polymorphism (NQO1*2 allele) in the human NQO1 gene. This
      mutation has been characterized as a genetic polymorphism (NQO1*2), which leads
      to greatly diminished levels of protein due to rapid degradation of the NQO1*2
      protein by the ubiquitin proteasomal pathway (UPP). In an attempt to decipher the
      mechanism responsible for the differential stability of wild-type NQO1*1 and
      mutant NQO1*2 proteins, we have investigated the interactions of these proteins
      with molecular chaperones of the Hsp family. Using co-immunoprecipitation studies
      (co-IPs), no association was observed between Hsp90 and either wild-type NQO1*1
      or mutant NQO1*2 proteins. Hsp70, however, was found to associate with NQO1*1
      protein in cells when co-IPs were performed with an anti-NQO1 antibody followed
      by immunoblotting with an anti-Hsp70 antibody or vice versa. Hsp40 could also be
      detected in the immunoprecipitated protein complex. Experiments were also
      performed using either the NQO1*1 or NQO1*2 coding regions in an in vitro
      transcription/translation system employing rabbit reticulocyte lysates (RRLs).
      Consistent with the cellular data, co-IP experiments in RRLs demonstrated an
      association of Hsp70 with wild-type NQO1*1 protein but not with NQO1*2 protein.
      To further elucidate the role of the association of Hsp70 with the NQO1*1
      protein, site-directed mutagenesis was used to modify a proposed Hsp70 binding
      site near the N terminus of the NQO1 protein. We generated a plasmid containing
      an NQO1*1 coding region with a mutated Hsp70 binding site (isoleucine to aspartic
      acid at position 8, NQO1*1/I8D). In contrast to the NQO1*1 protein translated in
      RRLs, the NQO1*1/I8D protein did not associate with Hsp70, as demonstrated by co
      IP, was catalytically inactive, and was degraded by the UPP. These data suggest
      that the association of Hsp70 with NQO1*1 may play an important role in the
      stability and functionality of the NQO1 protein.

PMID- 11821414
TI  - Synergy between extracellular modules of vascular endothelial cadherin promotes
      homotypic hexameric interactions.
AB  - Vascular endothelial (VE) cadherin is an endothelial specific cadherin that plays
      a major role in remodeling and maturation of vascular vessels. Recently, we
      presented evidence that the extracellular part of VE cadherin, which consists of
      five homologous modules, associates as a Ca(2+)-dependent hexamer in solution
      (Legrand, P., Bibert, S., Jaquinod, M., Ebel, C., Hewat, E., Vincent, F.,
      Vanbelle, C., Concord, E., Vernet, T., and Gulino, D. (2001) J. Biol. Chem. 276,
      3581-3588). In an effort to identify which extracellular modules are involved in
      the elaboration and stability of this hexameric structure, we expressed various
      VE cadherin-derived fragments overlapping individual or multiple successive
      modules as soluble proteins, purified each to homogeneity, and tested their
      propensity to self-associate. Altogether, the results demonstrate that, as their
      length increases, VE cadherin recombinant fragments generate increasingly complex
      self-associating structures; although single module fragments do not oligomerize,
      some two or three module-containing fragments self-assemble as dimers, and four
      module-containing fragments associate as hexamers. Our results also suggest that,
      before elaborating a hexameric structure, molecules of VE cadherin self-assemble
      as intermediate dimers. A synergy between the extracellular modules of VE
      cadherin is thus required to build homotypic interactions. Placed in a cellular
      context, this particular self-association mode may reflect the distinctive
      biological requirements imposed on VE cadherin at adherens junctions in the
      vascular endothelium.

PMID- 11821415
TI  - ERK activation mediates cell cycle arrest and apoptosis after DNA damage
      independently of p53.
AB  - In response to DNA damage, ataxia-telangiectasia mutant and ataxia-telangiectasia
      and Rad-3 activate p53, resulting in either cell cycle arrest or apoptosis. We
      report here that DNA damage stimuli, including etoposide (ETOP), adriamycin
      (ADR), ionizing irradiation (IR), and ultraviolet irradiation (UV) activate
      ERK1/2 (ERK) mitogen-activated protein kinase in primary (MEF and IMR90),
      immortalized (NIH3T3) and transformed (MCF-7) cells. ERK activation in response
      to ETOP was abolished in ATM-/- fibroblasts (GM05823) and was independent of p53.
      The MEK1 inhibitor PD98059 prevented ERK activation but not p53 stabilization.
      Maximal ERK activation in response to DNA damage was not attenuated in MEF(p53-/
      ). However, ERK activation contributes to either cell cycle arrest or apoptosis
      in response to low or high intensity DNA insults, respectively. Inhibition of ERK
      activation by PD98059 or U0126 attenuated p21(CIP1) induction, resulting in
      partial release of the G(2)/M cell cycle arrest induced by ETOP. Furthermore,
      PD98059 or U0126 also strongly attenuated apoptosis induced by high dose ETOP,
      ADR, or UV. Conversely, enforced activation of ERK by overexpression of MEK
      1/Q56P sensitized cells to DNA damage-induced apoptosis. Taken together, these
      results indicate that DNA damage activates parallel ERK and p53 pathways in an
      ATM-dependent manner. These pathways might function cooperatively in cell cycle
      arrest and apoptosis.

PMID- 11821416
TI  - Nonstructural 5A protein of hepatitis C virus modulates tumor necrosis factor
      alpha-stimulated nuclear factor kappa B activation.
AB  - The hepatitis C virus nonstructural protein 5A (NS5A) is a multifunctional
      phosphoprotein that leads to pleiotropic responses, in part by regulating cell
      growth and cellular signaling pathways. Here we show that overexpression of NS5A
      inhibits tumor necrosis factor (TNF)-alpha-induced nuclear factor kappaB (NF
      kappaB) activation in HEK293 cells, as determined by luciferase reporter gene
      expression and by electrophoretic mobility shift assay. When overexpressed, NS5A
      cannot inhibit the recruitment of TNF receptor-associated factor 2 (TRAF2) and
      IkappaB kinase (IKK)beta into the TNF receptor 1-TNF receptor-associated death
      domain complex. In contrast, NS5A is a part of the TNF receptor 1 signaling
      complex. NF-kappaB activation by TNF receptor-associated death domain and TRAF2
      was inhibited by NS5A, whereas MEKK1 and IKKbeta-dependent NF-kappaB activation
      was not affected, suggesting that NS5A may inhibit NF-kappaB activation signaled
      by TRAF2. Coimmunoprecipitation and colocalization of NS5A and TRAF2 expressed in
      vivo provide compelling evidence that NS5A directly interacts with TRAF2. This
      interaction was mapped to the middle one-third (amino acids 148-301) of NS5A and
      the TRAF domain of TRAF2. Our findings suggest a possible molecular mechanism
      that could explain the ability of NS5A to negatively regulate TNF-alpha-induced
      NF-kappaB activation.

PMID- 11821417
TI  - DNA polymerase lambda, a novel DNA repair enzyme in human cells.
AB  - DNA polymerase lambda (pol lambda) is a novel family X DNA polymerase that has
      been suggested to play a role in meiotic recombination and DNA repair. The recent
      demonstration of an intrinsic 5'-deoxyribose-5-phosphate lyase activity in pol
      lambda supports a function of this enzyme in base excision repair. However, the
      biochemical properties of the polymerization activity of this enzyme are still
      largely unknown. We have cloned and purified human pol lambda to homogeneity in a
      soluble and active form, and we present here a biochemical description of its
      polymerization features. In support of a role in DNA repair, pol lambda inserts
      nucleotides in a DNA template-dependent manner and is processive in small gaps
      containing a 5'-phosphate group. These properties, together with its nucleotide
      insertion fidelity parameters and lack of proofreading activity, indicate that
      pol lambda is a novel beta-like DNA polymerase. However, the high affinity of pol
      lambda for dNTPs (37-fold over pol beta) is consistent with its possible
      involvement in DNA transactions occurring under low cellular levels of dNTPs.
      This suggests that, despite their similarities, pol beta and pol lambda have
      nonredundant in vivo functions.

PMID- 11821418
TI  - Characterization and expression analysis of Staphylococcus aureus pathogenicity
      island 3. Implications for the evolution of staphylococcal pathogenicity islands.
AB  - We describe the complete sequence of the 15.9-kb staphylococcal pathogenicity
      island 3 encoding staphylococcal enterotoxin serotypes B, K, and Q. The island,
      which meets the generally accepted definition of pathogenicity islands, contains
      24 open reading frames potentially encoding proteins of more than 50 amino acids,
      including an apparently functional integrase. The element is bordered by two 17
      bp direct repeats identical to those found flanking staphylococcal pathogenicity
      island 1. The island has extensive regions of homology to previously described
      pathogenicity islands, particularly staphylococcal pathogenicity islands 1 and
      bov. The expression of 22 of the 24 open reading frames contained on
      staphylococcal pathogenicity island 3 was detected either in vitro during growth
      in a laboratory medium or serum or in vivo in a rabbit model of toxic shock
      syndrome using DNA microarrays. The effect of oxygen tension on staphylococcal
      pathogenicity island 3 gene expression was also examined. By comparison with the
      known staphylococcal pathogenicity islands in the context of gene expression
      described here, we propose a model of pathogenicity island origin and evolution
      involving specialized transduction events and addition, deletion, or
      recombination of pathogenicity island "modules."

PMID- 11821420
TI  - Preferential misincorporation of purine nucleotides by human DNA polymerase eta
      opposite benzo[a]pyrene 7,8-diol 9,10-epoxide deoxyguanosine adducts.
AB  - Human DNA polymerase eta was used to copy four stereoisomeric deoxyguanosine (dG)
      adducts derived from benzo[a]pyrene 7,8-diol 9,10-epoxide (diastereomer with the
      7-hydroxyl group and epoxide oxygen trans (BaP DE-2)). The adducts, formed by
      either cis or trans epoxide ring opening of each enantiomer of BaP DE-2 by N(2)
      of dG, were placed at the fourth nucleotide from the 5'-end in two 16-mer
      sequence contexts, 5' approximately CG*A approximately and 5' approximately GG*T.
      poleta was remarkably error prone at all four diol epoxide adducts, preferring to
      misincorporate G and A at frequencies 3- to more than 50-fold greater than the
      frequencies for T or the correct C, although the highest rates were 60-fold below
      the rate of incorporation of C opposite a non-adducted G. Anti to syn rotation of
      the adducted base, consistent with previous NMR data for a BaP DE-2 dG adduct
      placed just beyond a primer terminus, provides a rationale for preferring purine
      misincorporation. Extension of purine misincorporations occurred preferentially,
      but extension beyond the adduct site was weak with V(max)/K(m) values generally
      10-fold less than for misincorporation. Mostly A was incorporated opposite (+)
      BaP DE-2 dG adducts, which correlates with published observations that G --> T is
      the most common type of mutation that (+)-BaP DE-2 induces in mammalian cells.

PMID- 11821419
TI  - Determination of substrate motifs for human Chk1 and hCds1/Chk2 by the oriented
      peptide library approach.
AB  - Mammalian Chk1 and Chk2 are two Ser/Thr effector kinases that play critical roles
      in DNA damage-activated cell cycle checkpoint signaling pathways downstream of
      ataxia telangiectasia-mutated and ataxia telangiectasia-related. Endogenous
      substrates have been identified for human hCds1/Chk2 and Chk1; however, the
      sequences surrounding the substrate residues appear unrelated, and consensus
      substrate motifs for the two Ser/Thr kinases remain unknown. We have utilized
      peptide library analyses to develop specific, highly preferred substrate motifs
      for hCds1/Chk2 and Chk1. The optimal motifs are similar for both kinases and most
      closely resemble the previously identified Chk1 and hCds1/Chk2 substrate target
      sequences in Cdc25C and Cdc25A, the regulation of which plays an important role
      in S and G(2)M arrest. Essential residues required for the definition of the
      optimal motifs were also identified. Utilization of the peptides to assay the
      substrate specificities and catalytic activities of Chk1 and hCds1/Chk2 revealed
      substantial differences between the two Ser/Thr kinases. Structural modeling
      analyses of the peptides into the Chk1 catalytic cleft were consistent with Chk1
      kinase assays defining substrate suitability. The library-derived substrate
      preferences were applied in a genome-wide search program, revealing novel targets
      that might serve as substrates for hCds1/Chk2 or Chk1 kinase activity.

PMID- 11821421
TI  - Autocatalytic mechanism and consequences of covalent heme attachment in the
      cytochrome P4504A family.
AB  - The prosthetic heme group in the CYP4A family of cytochrome P450 enzymes is
      covalently attached to an I-helix glutamic acid residue. This glutamic acid is
      conserved in the CYP4 family but is absent in other P450 families. As shown here,
      the glutamic acid is linked, presumably via an ester bond, to a hydroxyl group on
      the heme 5-methyl group. Mutation of the glutamic acid to an alanine in CYP4A1,
      CYP4A3, and CYP4A11 suppresses covalent heme binding. In wild-type CYP4A3 68% of
      the heme is covalently bound to the heterologously expressed protein, but in the
      CYP4A3/E318D mutant, 47% of the heme is unchanged, 47% is present as
      noncovalently bound 5-hydroxymethylheme, and only 6% is covalently bound to the
      protein. In the CYP4A3/E318Q mutant, the majority of the heme is unaltered, and
      <2% is covalently linked. The proportion of covalently bound heme in the
      recombinant CYP4A proteins increases with time under turnover conditions. The
      catalytic activity is sensitive in some, but not all, CYP4A enzymes to the extent
      of covalent heme binding. Mutations of Glu(318) in CYP4A3 decrease the apparent
      k(cat) values for lauric acid hydroxylation. The key conclusions are that (a)
      covalent heme binding occurs via an ester bond to the heme 5-methyl group, (b)
      covalent binding of the heme is mediated by an autocatalytic process, and (c)
      fatty acid oxidation is sensitive in some CYP4A enzymes to the presence or
      absence of the heme covalent link.

PMID- 11821422
TI  - Resonance Raman and ligand binding studies of the oxygen-sensing signal
      transducer protein HemAT from Bacillus subtilis.
AB  - HemAT-Bs is a heme-containing signal transducer protein responsible for aerotaxis
      of Bacillus subtilis. The recombinant HemAT-Bs expressed in Escherichia coli was
      purified as the oxy form in which oxygen was bound to the ferrous heme. Oxygen
      binding and dissociation rate constants were determined to be k(on) = 32 microm(
      1) s(-1) and k(off) = 23 s(-1), respectively, revealing that HemAT-Bs has a
      moderate oxygen affinity similar to that of sperm whale myoglobin (Mb). The rate
      constant for autoxidation at 37 degrees C was 0.06 h(-1), which is also close to
      that of Mb. Although the electronic absorption spectra of HemAT-Bs were similar
      to those of Mb, HemAT-Bs showed some unique characteristics in its resonance
      Raman spectra. Oxygen-bound HemAT-Bs gave the nu(Fe-O(2)) band at a noticeably
      low frequency (560 cm(-1)), which suggests a unique hydrogen bonding between a
      distal amino acid residue and the proximal atom of the bound oxygen molecule.
      Deoxy HemAT-Bs gave the nu(Fe-His) band at a higher frequency (225 cm(-1)) than
      those of ordinary His-coordinated deoxy heme proteins. CO-bound HemAT-Bs gave the
      nu(Fe-CO) and nu(C-O) bands at 494 and 1964 cm(-1), respectively, which fall on
      the same nu(C-O) versus nu(Fe-CO) correlation line as that of Mb. Based on these
      results, the structural and functional properties of HemAT-Bs are discussed.

PMID- 11821423
TI  - Transcription-coupled DNA repair is genomic context-dependent.
AB  - DNA damage is preferentially repaired in the transcribed strand of many active
      genes. Although the concept of DNA repair coupled with transcription has been
      widely accepted, its mechanisms remain elusive. We recently reported that in
      Chinese hamster ovary cells while ultraviolet light-induced cyclobutane
      pyrimidine dimers (CPDs) are preferentially repaired in the transcribed strand of
      dihydrofolate reductase gene, CPDs are efficiently repaired in both strands of
      adenine phosphoribosyltransferase (APRT) locus, in either a transcribed or
      nontranscribed APRT gene (1). These results suggested that the transcription
      dependence of repair may depend on genomic context. To test this hypothesis, we
      constructed transfectant cell lines containing a single, actively transcribed
      APRT gene, integrated at different genomic sites. Mapping of CPD repair in the
      integrated APRT genes in three transfectant cell lines revealed two distinct
      repair patterns, either preferential repair of CPDs in the transcribed strand or
      very poor repair in both strands. Similar kinetics of micrococcal nuclease
      digestion were seen for all three transfectant APRT gene domains and endogenous
      APRT locus. Our results suggest that both the efficiency and strand-specificity
      of repair of an actively transcribed gene are profoundly affected by genomic
      context but do not reflect changes in first order nucleosomal structure.

PMID- 11821424
TI  - Role of tyrosine kinase Jak2 in prolactin-induced differentiation and growth of
      mammary epithelial cells.
AB  - Genetic studies in mice have established a critical role for prolactin receptors
      and transcription factor Stat5 in mammary gland differentiation. However, the
      enzymatic coupling between prolactin receptors and Stat5 in this process has not
      been established. In addition to Jak2, several other tyrosine kinases reportedly
      also are associated with prolactin receptors and may phosphorylate Stat5. Because
      Jak2 null mice die in utero, we targeted Jak2 in an ex vivo model of prolactin
      induced mammary epithelial cell differentiation to determine the role of Jak2 in
      regulation of cell differentiation and growth. Two independent targeting
      strategies were used to suppress Jak2 in immortalized HC11 mouse mammary
      epithelial cells: 1) stable expression of a specific Jak2 antisense construct and
      2) adenoviral delivery of a dominant-negative Jak2 gene. We now demonstrate that
      Jak2 is essential for prolactin-induced differentiation and activation of Stat5
      in normal mouse mammary epithelial cells. Furthermore, suppression of Jak2 in
      HC11 cells was associated with constitutive activation of oncoprotein Stat3 and a
      hyperproliferative phenotype characterized by increased mitotic rate, reduced
      apoptosis, and reduced contact inhibition. Collectively, our data suggest that
      Jak2 is differentiation-inducing and growth-inhibitory in normal mammary
      epithelial cells, observations that may shed new light on the role of the Jak2
      Stat5 pathway in breast cancer.

PMID- 11821425
TI  - Molecular cloning and characterization of a novel UDP-GlcNAc:GalNAc-peptide
      beta1,3-N-acetylglucosaminyltransferase (beta 3Gn-T6), an enzyme synthesizing the
      core 3 structure of O-glycans.
AB  - The core 3 structure of the O-glycan, GlcNAcbeta1-3GalNAcalpha1-serine/threonine,
      an important precursor in the biosynthesis of mucin-type glycoproteins, is
      synthesized by UDP-N-acetylglucosamine:GalNAc-peptide beta1,3-N-
      acetylglucosaminyltransferase (beta3Gn-T; core 3 synthase). The core 3 structure
      is restricted in its occurrence to mucins from specific tissues such as the
      stomach, small intestine, and colon. A partial sequence encoding a novel member
      of the human beta3Gn-T family was found in one of the data bases. We cloned a
      complementary DNA of this gene and named it beta3Gn-T6. The putative amino acid
      sequence of beta3Gn-T6 retains the beta3Gn-T motifs and is predicted to comprise
      a typical type II membrane protein. The soluble form of beta3Gn-T6 expressed in
      insect cells showed beta3Gn-T activity toward GalNAcalpha-p-nitrophenyl and
      GalNAcalpha1-serine/threonine. The beta1,3-linkage between GlcNAc and GalNAc of
      the enzyme reaction product was confirmed by high performance liquid
      chromatography and NMR analyses. beta3Gn-T6 effectively transferred a GlcNAc to
      the GalNAc residue on MUC1 mucin, resulting in the synthesis of a core 3
      structure. Real time PCR analysis revealed that the beta3Gn-T6 transcript was
      restricted in its distribution, mainly to the stomach, colon, and small
      intestine. We concluded that beta3Gn-T6 is the most logical candidate for the
      core 3 synthase, which plays an important role in the synthesis of mucin-type O
      glycans in digestive organs.

PMID- 11821426
TI  - Physical and functional interaction between the mini-chromosome maintenance-like
      DNA helicase and the single-stranded DNA binding protein from the crenarchaeon
      Sulfolobus solfataricus.
AB  - Mini-chromosome Maintenance (MCM) proteins play an essential role in both
      initiation and elongation phases of DNA replication in Eukarya. Genes encoding
      MCM homologs are present also in the genomic sequence of Archaea and the MCM-like
      protein from the euryarchaeon Methanobacterium thermoautotrophicum (Mth MCM) was
      shown to possess a robust ATP-dependent 3'-5' DNA helicase activity in vitro.
      Herein, we report the first biochemical characterization of a MCM homolog from a
      crenarchaeon, the thermoacidophile Sulfolobus solfataricus (Sso MCM). Gel
      filtration and glycerol gradient centrifugation experiments indicate that the Sso
      MCM forms single hexamers (470 kDa) in solution, whereas the Mth MCM assembles
      into double hexamers. The Sso MCM has NTPase and DNA helicase activity, which
      preferentially acts on DNA duplexes containing a 5'-tail and is stimulated by the
      single-stranded DNA binding protein from S. solfataricus (Sso SSB). In support of
      this functional interaction, we demonstrated by immunological methods that the
      Sso MCM and SSB form protein.protein complexes. These findings provide the first
      in vitro biochemical evidence of a physical/functional interaction between a MCM
      complex and another replication factor and suggest that the two proteins may
      function together in vivo in important DNA metabolic pathways.

PMID- 11821427
TI  - The Salmonella typhimurium flagellar basal body protein FliE is required for
      flagellin production and to induce a proinflammatory response in epithelial
      cells.
AB  - During apical colonization by Salmonella typhimurium, intestinal epithelial cells
      orchestrate a proinflammatory response that involves secretion of
      chemoattractants, predominantly interleukin-8, which coordinate neutrophil trans
      epithelial migration at the site of infection. This host-pathogen interaction
      requires several S. typhimurium genes. To identify novel genes that participate
      in this pathogen-induced proinflammatory response, we created S. typhimurium Tn
      10 transposon mutants and identified a single mutant with Tn-10 insertional
      inactivation within the fliE flagellar locus that was able to adhere to and
      invade intestinal epithelial cells normally but was unable to induce interleukin
      8 secretion in host cells. The fliE-deficient mutant failed to secrete flagellin
      and lacked any surface assembly of flagellae. Unlike wild-type S. typhimurium,
      the fliE-deficient mutant did not activate the IkappaBalpha/NF-kappaB signaling
      pathway or induce the coordinated trans-epithelial migration of isolated human
      neutrophils. Transcomplementation of the fliE-deficient mutant with a wild-type
      fliE-harboring plasmid restored all defects and produced a wild-type S.
      typhimurium phenotype. Furthermore, functional down-regulation of basolateral
      TLR5 completely inhibited the monolayers' ability to respond to both wild-type S.
      typhimurium and purified flagellin but had no affect on tumor necrosis factor
      alpha-induced responses. We therefore conclude that S. typhimurium fliE is
      essential for flagellin secretion, flagellar assembly, and S. typhimurium-induced
      proinflammatory responses through basolateral TLR5 and is consistent with the
      emerging model of S. typhimurium flagellin-induced inflammation.

PMID- 11821428
TI  - Drosophila segment polarity gene product porcupine stimulates the
      posttranslational N-glycosylation of wingless in the endoplasmic reticulum.
AB  - Wnt is a family of cysteine-rich secreted glycoproteins, which controls the fate
      and behavior of the cells in multicellular organisms. In the absence of
      Drosophila segment polarity gene porcupine (porc), which encodes an endoplasmic
      reticulum (ER) multispanning transmembrane protein, the N-glycosylation of
      Wingless (Wg), one of Drosophila Wnt family, is impaired. In contrast, the
      ectopic expression of porc stimulates the N-glycosylation of both endogenously
      and exogenously expressed Wg. The N-glycosylation of Wg in the ER occurs
      posttranslationally, while in the presence of dithiothreitol, it efficiently
      occurs cotranslationally. Thus, the cotranslational disulfide bond formation of
      Wg competes with the N-glycosylation by an oligosaccharyl transferase complex.
      Porc binds the N-terminal 24-amino acid domain (residues 83-106) of Wg, which is
      highly conserved in the Wnt family and stimulates the N-glycosylation at
      surrounding sites. Porc is also necessary for the processing of Drosophila Wnt
      3/5 in both embryos and cultured cells. Thus, Porc binds the N-terminal specific
      domain of the Wnt family and stimulates its posttranslational N-glycosylation by
      anchoring them at the ER membrane possibly through acylation.

PMID- 11821429
TI  - Targeting, insertion, and localization of Escherichia coli YidC.
AB  - YidC was recently shown to play an important role in the assembly of inner
      membrane proteins (IMPs) both in conjunction with and separate from the Sec
      translocon. Little is known about the biogenesis and structural and functional
      properties of YidC, itself a polytopic IMP. Here we analyze the targeting and
      membrane integration of YidC using in vivo and in vitro approaches. The combined
      data indicate that YidC is targeted by the signal recognition particle and
      inserts at the SecAYEG-YidC translocon early during biogenesis, unlike its
      mitochondrial homologue Oxa1p. In addition, YidC is shown to be relatively
      abundant compared with other components involved in IMP assembly and is
      predominantly localized at the poles of the cell.

PMID- 11821430
TI  - The histone deacetylase inhibitor trichostatin A blocks progesterone receptor
      mediated transactivation of the mouse mammary tumor virus promoter in vivo.
AB  - Post-translational modifications of histones play an important role in modulating
      gene transcription within chromatin. We used the mouse mammary tumor virus (MMTV)
      promoter, which adopts an ordered nucleosomal structure, to investigate the
      impact of a specific inhibitor of histone deacetylase, trichostatin A (TSA), on
      progesterone receptor-activated transcription. TSA induced global histone
      hyperacetylation, and this effect occurred independently of the presence of
      hormone. Interestingly, chromatin immunoprecipitation analysis revealed no
      significant change in the level of acetylated histones associated with the MMTV
      promoter following high TSA treatment. In human breast cancer cells, in which the
      MMTV promoter adopts a constitutively "open" chromatin structure, treatment with
      TSA converted the MMTV promoter into a closed structure. Addition of hormone did
      not overcome this TSA-induced closure of the promoter chromatin. Furthermore, TSA
      treatment resulted in the eviction of the transcription factor nuclear factor-1
      from the promoter and reduced progesterone receptor-induced transcription.
      Kinetic experiments revealed that a loss of chromatin-remodeling proteins was
      coincident with the decrease in MMTV transcriptional activity and the imposition
      of repressed chromatin architecture at the promoter. These results demonstrate
      that deacetylase inhibitor treatment at levels that induce global histone
      acetylation may leave specific regulatory regions relatively unaffected and that
      this treatment may lead to transcriptional inhibition by mechanisms that modify
      chromatin-remodeling proteins rather than by influencing histone acetylation of
      the local promoter chromatin structure.

PMID- 11821431
TI  - Oversulfated chondroitin/dermatan sulfates containing GlcAbeta1/IdoAalpha1
      3GalNAc(4,6-O-disulfate) interact with L- and P-selectin and chemokines.
AB  - We previously reported that versican, a large chondroitin/dermatan sulfate
      (CS/DS) proteoglycan, interacts through its CS/DS chains with adhesion molecules
      L- and P-selectin and CD44, as well as chemokines. Here, we have characterized
      these interactions further. Using a metabolic inhibitor of sulfation, sodium
      chlorate, we show that the interactions of the CS/DS chains of versican with L-
      and P-selectin and chemokines are sulfation-dependent but the interaction with
      CD44 is sulfation-independent. Consistently, versican's binding to L- and P
      selectin and chemokines is specifically inhibited by oversulfated CS/DS chains
      containing GlcAbeta1-3GalNAc(4,6-O-disulfate) or IdoAalpha1-3GalNAc(4,6-O
      disulfate), but its binding to CD44 is inhibited by all the CS/DS chains,
      including low-sulfated and unsulfated ones. Affinity and kinetic analyses using
      surface plasmon resonance revealed that the oversulfated CS/DS chains containing
      GlcAbeta1/IdoAalpha1-3GalNAc(4,6-O-disulfate) bind directly to selectins and
      chemokines with high affinity (K(d) 21.1 to 293 nm). In addition, a
      tetrasaccharide fragment of repeating GlcAbeta1-3GalNAc(4,6-O-disulfate) units
      directly interacts with L- and P-selectin and chemokines and oversulfated CS/DS
      chains containing GlcAbeta1/IdoAalpha1-3GalNAc(4,6-O-disulfate) inhibit chemokine
      induced Ca(2+) mobilization. Taken together, our results show that oversulfated
      CS/DS chains containing GlcAbeta1/IdoAalpha1-3GalNAc(4,6-O-disulfate) are
      recognized by L- and P-selectin and chemokines, and imply that these chains are
      important in selectin- and/or chemokine-mediated cellular responses.

PMID- 11821432
TI  - An imprinted PEG1/MEST antisense expressed predominantly in human testis and in
      mature spermatozoa.
AB  - PEG1 (or MEST) is an imprinted gene located on human chromosome 7q32 that is
      expressed predominantly from the paternal allele. In the mouse, Peg1/Mest is
      associated with embryonic growth and maternal behavior. Human PEG1 is transcribed
      from two promoters; the transcript from promoter P1 is derived from both parental
      alleles, and the transcript from P2 is exclusively from the paternal allele. We
      characterized the P1 and P2 transcripts in various normal and neoplastic tissues.
      In the normal tissues, PEG1 was transcribed from both promoters P1 and P2,
      whereas in six of eight neoplastic tissues, PEG1 was transcribed exclusively from
      promoter P1. Bisulfite sequencing demonstrated high levels of CpG methylation in
      the P2 region of DNA from a lung tumor. In the region between P1 and P2, we
      identified a novel transcript, PEG1-AS, in an antisense orientation to PEG1. PEG1
      AS is a spliced transcript and was detected as a strong 2.4-kilobase band on a
      Northern blot. PEG1-AS and PEG1 P2-sense transcript were expressed exclusively
      from the paternal allele. Fragments of DNA from within the 1.5-kilobase region
      between PEG1-AS and the P2 exon were ligated to a pGL3 luciferase reporter vector
      and transfected into NCI H23 cells. This DNA exhibited strong promoter activity
      in both the sense and antisense directions, indicating that PEG1-AS and P2 exon
      share a common promoter region. Treatment of the transfected DNA fragments with
      CpG methylase abolished the promoter activity. Of interest, PEG1-AS was expressed
      predominantly in testis and in mature motile spermatozoa, indicating a possible
      role for this transcript in human sperm physiology and fertilization.

PMID- 11821433
TI  - Uniport of NH4+ by the root hair plasma membrane ammonium transporter LeAMT1;1.
AB  - The transport of ammonium/ammonia is a key process for the acquisition and
      metabolism of nitrogen. Ammonium transport is mediated by the AMT/MEP/Rh family
      of membrane proteins which are found in microorganisms, plants, and animals,
      including the Rhesus blood group antigens in humans. Although ammonium
      transporters from all kingdoms have been functionally expressed and partially
      characterized, the transport mechanism, as well as the identity of the true
      substrate (NH(4+) or NH(3)) remains unclear. Here we describe the functional
      expression and characterization of LeAMT1;1, a root hair ammonium transporter
      from tomato (Lycopersicon esculentum) in Xenopus oocytes. Micromolar
      concentrations of external ammonium were found to induce concentration- and
      voltage-dependent inward currents in oocytes injected with LeAMT1;1 cRNA, but not
      in water-injected control oocytes. The NH(4+)-induced currents were more than 3
      fold larger than methylammonium currents and were not subject to inhibition by
      Na(+) or K(+). The voltage dependence of the affinity of LeAMT1;1 toward its
      substrate strongly suggests that charged NH(4+), rather than NH(3), is the true
      transport substrate. Furthermore, ammonium transport was independent of the
      external proton concentration between pH 5.5 and pH 8.5. LeAMT1;1 is concluded to
      mediate potential-driven NH(4+) uptake and retrieval depending on root membrane
      potential and NH(4+) concentration gradient.

PMID- 11821434
TI  - The Erbin PDZ domain binds with high affinity and specificity to the carboxyl
      termini of delta-catenin and ARVCF.
AB  - Erbin is a recently described member of the LAP (leucine-rich repeat and PDZ
      domain) protein family. We used a C-terminally displayed phage peptide library to
      identify optimal ligands for the Erbin PDZ domain. Phage-selected peptides were
      type 1 PDZ ligands that bound with high affinity and specificity to the Erbin PDZ
      domain in vitro. These peptides most closely resembled the C-terminal PDZ domain
      binding motifs of three p120-related catenins: delta-catenin, ARVCF, and p0071
      (DSWV-COOH). Analysis of the interactions of the Erbin PDZ domain with synthetic
      peptides matching the C termini of ARVCF or delta-catenin also demonstrated
      specific high affinity binding. We characterized the interactions between the
      Erbin PDZ domain and both ARVCF and delta-catenin in vitro and in vivo. The Erbin
      PDZ domain co-localized and coprecipitated with ARVCF or delta-catenin complexed
      with beta-catenin and E/N-cadherin. Mutagenesis and peptide competition
      experiments showed that the association of Erbin with the cadherin-catenin
      complex was mediated by the interaction of its PDZ domain with the C-terminal PDZ
      domain-binding motifs (DSWV-COOH) of ARVCF and delta-catenin. Finally, we showed
      that endogenous delta-catenin and Erbin co-localized in and co-immunoprecipitated
      from neurons. These results suggest that delta-catenin and ARVCF may function to
      mediate the association of Erbin with the junctional cadherin-catenin complex.
      They also demonstrate that C-terminal phage-display technology can be used to
      predict physiologically relevant ligands for PDZ domains.

PMID- 11821435
TI  - PLIF, a novel human ferritin subunit from placenta with immunosuppressive
      activity.
AB  - Ferritin is a ubiquitous iron storage protein existing in multiple isoforms
      composed of 24 heavy and light chain subunits. We describe here a third ferritin
      related subunit cloned from human placenta cDNA library and named PLIF (placental
      immunomodulatory ferritin). The PLIF coding region is composed of ferritin heavy
      chain (FTH) sequence lacking the 65 C-terminal amino acids, which are substituted
      with a novel 48 amino acid domain (C48). In contrast to FTH, PLIF mRNA does not
      include the iron response element in the 5'-untranslated region, suggesting that
      PLIF synthesis is not regulated by iron. The linkage between the FTH and C48
      domains created a restriction site for EcoRI. PLIF protein was found to localize
      in syncytiotrophoblasts of placentas (8 weeks of gestation) at the fetal-maternal
      interface. Increased levels of PLIF transcript and protein were also detected in
      the breast carcinoma cell lines T47D and MCF-7 but not in the benign
      corresponding cell line HBL-100. In vitro, PLIF was shown to down-modulate mixed
      lymphocyte reactions and to inhibit the proliferation of peripheral blood
      mononuclear cells stimulated with OKT3. The accumulated data indicate that PLIF
      is an embryonic immune factor involved in down-modulating the maternal immune
      recognition of the embryo toward anergy. This mechanism may have been adapted by
      breast cancer cells over expressing PLIF.

PMID- 11821436
TI  - New treatments for advanced Hodgkin's disease: an uphill fight beginning close to
      the top.

PMID- 11821437
TI  - Tumor hypoxia: chicken, egg, or a piece of the farm?

PMID- 11821438
TI  - Why do we still use hormone replacement therapy? Why don't we use it more?

PMID- 11821439
TI  - Can we cure limited metastatic breast cancer?

PMID- 11821440
TI  - Attending to psychologic symptoms and palliative care.

PMID- 11821441
TI  - Prognostic factors for sarcomas: hard and soft.

PMID- 11821442
TI  - Stanford V and radiotherapy for locally extensive and advanced Hodgkin's disease:
      mature results of a prospective clinical trial.
AB  - PURPOSE: To provide more mature data on the efficacy and complications of a
      brief, dose-intense chemotherapy regimen plus radiation therapy (RT) to bulky
      disease sites for locally extensive and advanced-stage Hodgkin's disease.
      PATIENTS AND METHODS: One hundred forty-two patients with stage III or IV or
      locally extensive mediastinal stage I or II Hodgkin's disease received Stanford V
      chemotherapy for 12 weeks followed by 36-Gy RT to initial sites of bulky (> or =5
      cm) or macroscopic splenic disease. Freedom from progression (FFP), overall
      survival (OS), and freedom from second relapse (FF2R) were determined using life
      table estimates. Outcomes were analyzed according to the international prognostic
      score. Late effects of treatment were recorded in follow-up. RESULTS: With a
      median follow-up of 5.4 years, the 5-year FFP was 89% and the OS was 96%. No
      patient progressed during treatment, and there were no treatment-related deaths.
      FFP was significantly superior among patients with a prognostic score of 0 to 2
      compared with those with a score of 3 and higher (94% v 75%, P <.0001). No
      secondary leukemia was observed. To date, there have been 42 pregnancies after
      treatment. Among 16 patients who relapsed, the FF2R was 69% at 5 years.
      CONCLUSION: These data confirm our preliminary report that Stanford V
      chemotherapy with RT to bulky disease sites is highly effective in locally
      extensive and advanced Hodgkin's disease. It is most important to compare this
      approach with standard doxorubicin, bleomycin, vinblastine, and dacarbazine
      chemotherapy in the ongoing intergroup trial (E2496) to determine whether
      Stanford V with or without RT represents a therapeutic advance.

PMID- 11821443
TI  - Risk of second cancer in patients with hairy cell leukemia: long-term follow-up.
AB  - PURPOSE: The purpose of the present study was to assess the risk of second
      cancers in patients with hairy cell leukemia (HCL). PATIENTS AND METHODS: We
      investigated the incidence of additional cancers in those patients registered in
      the nationwide registry of the Italian Cooperative Group for the Study of HCL,
      asking the cooperating centers for additional information on initial and
      subsequent therapies and on time and type of second malignancies, if they
      developed. Here we report the final results of this survey, consisting of 54
      cases of second malignancies (excluding nine cases of epithelial skin cancer)
      which developed in 54 patients of 1,022 with adequate follow-up. RESULTS: The
      cumulative risk of development of a second cancer was 5%, 10%, and 14% at 5, 10,
      and 15 years, respectively. The incidence of second malignancies was not
      significantly higher than the expected rate (standardized incidence ratio [SIR],
      1.01; 95% confidence interval [CI], 0.74 to 1.33; P = 1.0). However, the SIR of
      non-Hodgkin's lymphoma in the entire cohort was 5.3 (95% CI, 1.9 to 11.5). Second
      malignancies occurred in eight (4.7%) of 386 patients who never received
      interferon (IFN), nine (5.9%) of 495 patients treated with IFN at the time of
      diagnosis, and seven (6.9%) of 102 patients who received IFN as second-line
      therapy. These differences were not statistically significant. Analysis of the
      separate calendar periods did not reveal any particular trends with respect to
      variations in SIR. CONCLUSION: The present study does not support the suspicion
      that patients with HCL are at increased risk of additional second malignancies,
      although the incidence of lymphoid neoplasms was significantly higher than
      expected. In addition, our data indicate that IFN therapy did not exert an
      oncogenic effect in such patients.

PMID- 11821444
TI  - Primary cutaneous follicular lymphoma: an assessment of clinical,
      histopathologic, immunophenotypic, and molecular features.
AB  - PURPOSE: Unlike nodal follicular lymphoma (NFL), Primary cutaneous follicular
      lymphomas (PCFLs) rarely express Bcl-2 protein or t(14;18)(q32;q21) (Bcl-2/IgH).
      The aim of this study was to further characterize PCFL in a large series from
      North America. PATIENTS AND METHODS: Clinical data and archival formalin-fixed,
      paraffin-embedded tissue were obtained from 32 patients. PCFL was defined as
      follicular lymphoma limited to the skin at the time of diagnosis and within the
      first 6 months after diagnosis. Specimens were analyzed for the expression of
      CD3, CD10, CD20, Bcl-2, and Bcl-6 proteins by immunohistochemistry as well as for
      the presence of t(14;18)(q32;q21) by polymerase chain reaction. RESULTS: The male
      to-female ratio was 1.5:1, with a median age of 60 years. Twenty-four patients
      had lesions on the head and neck, five had lesions on the trunk, and three had
      lesions on both head and trunk. Follow-up data were available in all cases, with
      a mean length of 35.8 months. The majority of the patients were treated with
      radiation therapy. All patients were alive at last follow-up except one.
      Recurrence was noted in seven patients (22%), after a mean disease-free survival
      time of 17.7 months. CD10 and Bcl-6 expression were seen in 29 (91%) of 32 and 31
      (97%) of 32 cases, respectively. Bcl-2 expression was noted in 13 (41%) of 32
      cases. PCR results for t(14;18)(q32;q21) were positive in 11 (34%) of 32 patients
      and showed correlation with Bcl-2 protein expression. The sequencing of the
      t(14;18)(q32;q21) amplicons confirmed unique breakpoints in each of the seven
      tested cases. Comparison between the Bcl-2 and/or t(14;18)(q32;q21)-positive and
      t(14;18)(q32;q21)-negative cases revealed no significant difference in age, site,
      clinical course, or outcome. CONCLUSION: We demonstrated Bcl-2 protein expression
      and t(14;18)(q32;q21) in a significant minority of cases, suggesting a
      relationship with NFL. It remains to be seen whether, on longer follow-up, there
      is any clinical difference in cases with and without t(14;18)(q32;q21).

PMID- 11821445
TI  - Phase II study of troxacitabine, a novel dioxolane nucleoside analog, in patients
      with refractory leukemia.
AB  - PURPOSE: To investigate the activity of a novel dioxolane L-nucleoside analog,
      troxacitabine (L-(-)-OddC, BCH-4556), in patients with refractory leukemia.
      PATIENTS AND METHODS: Study participants were patients with refractory or
      relapsed acute myeloid (AML) or lymphocytic (ALL) leukemia, myelodysplastic
      syndromes (MDS), or chronic myelogenous leukemia in blastic phase (CML-BP).
      Troxacitabine was provided as an intravenous infusion for more than 30 minutes
      daily for 5 days at a dose of 8.0 mg/m(2)/d (40 mg/m(2) per course). Courses were
      given every 3 to 4 weeks according to antileukemic efficacy. RESULTS: Forty-two
      patients (AML, 18 patients; MDS, one patient; ALL, six patients; CML-BP, 17
      patients) were treated. Median age was 51 years (range, 23 to 80 years); 22
      patients were male. Stomatitis was the most significant adverse event, with three
      patients (7%) and two patients (5%), respectively, experiencing grade 3 or 4
      toxicity. Ten patients (24%) had grade 3 hand-foot syndrome, and two patients
      (5%) had grade 3 skin rash. One patient (2%) had grade 3 fatigue and anorexia.
      Marrow hypoplasia occurred between days 14 and 28 in 12 (75%) of 16 assessable
      patients with AML. Two complete remissions and one partial remission (18%) were
      observed in 16 assessable patients with AML. None of six patients with ALL
      responded. Six (37%) of 16 assessable patients with CML-BP experienced a return
      to chronic-phase disease. CONCLUSION: Troxacitabine has significant antileukemic
      activity in patients with AML and CML-BP.

PMID- 11821446
TI  - Prolonged infusion of gemcitabine: clinical and pharmacodynamic studies during a
      phase I trial in relapsed acute myelogenous leukemia.
AB  - PURPOSE: To determine the maximum tolerated duration of infusions at the fixed
      gemcitabine dose rate of 10 mg/m(2)/min and to analyze the pharmacodynamic
      actions in leukemia blasts during gemcitabine therapy. PATIENTS AND METHODS: The
      study was conducted in a phase I trial by escalating the duration of gemcitabine
      infusion at a fixed-dose rate of 10 mg/m(2)/min. Patients with relapsed or
      refractory acute myelogenous leukemia (AML) received gemcitabine for 8.0 (n = 3),
      10.0 (n = 3), 12.5 (n = 8), 15.5 (n = 3), or 18.0 hours (n = 2). Pharmacokinetic
      and pharmacodynamic investigations were undertaken in circulating AML blasts.
      RESULTS: Gemcitabine was infused for up to 18 hours at the fixed-dose rate. Four
      patients had grade 3 toxicities at longer infusion schedules. One patient had a
      partial remission; two others had a reduction in blasts and concomitant rise in
      neutrophils. Gemcitabine triphosphate was detectable in AML cells even at 1 hour
      after the start of infusion in eight patients. The concentration ranged from 130
      to 900 micromol/L at the end of the infusion. Consistently, there was a rapid
      decline in DNA synthesis, which remained suppressed at 85% to 95% during and for
      at least 10 hours after the end of the infusion. Compared with levels in cells
      measured before therapy, at 8 hours after the start of the infusion, there was a
      decline in the cellular purine deoxynucleotide pools. CONCLUSION: At the fixed
      dose rate of 10 mg/m(2)/min, gemcitabine could be administered for longer than 12
      hours without untoward toxicity. The favorable toxicity profile and
      pharmacokinetic and pharmacodynamic features warrant combination with DNA
      damaging agents.

PMID- 11821447
TI  - Phase I evaluation of prolonged-infusion gemcitabine with mitoxantrone for
      relapsed or refractory acute leukemia.
AB  - PURPOSE: To ascertain the maximum tolerated duration of infusion of gemcitabine
      at 10 mg/m(2)/min in combination with mitoxantrone at 12 mg/m(2) daily for 3 days
      in the treatment of acute leukemia. PATIENTS AND METHODS: Thirty-four patients
      were enrolled. Stratum I consisted of 26 patients, median age 50 years (range, 25
      to 71 years), with relapsed or refractory leukemia. Stratum II contained eight
      patients, median age 62.5 years (range, 38 to 83 years), who had received fewer
      than three cycles of myelotoxic therapy for chronic myeloid leukemia or
      myelodysplasia that had evolved into leukemia. Patients received mitoxantrone at
      12 mg/m(2) daily for 3 days. After the first mitoxantrone dose, gemcitabine was
      provided intravenously at 10 mg/m(2)/min with the duration adjusted by following
      a continuous reassessment model. RESULTS: Severe myelosuppression, and stomatitis
      or esophagitis were the most common hematologic and nonhematologic dose-limiting
      toxicities. Several patients developed febrile neutropenia, nausea, or vomiting.
      In both strata, the maximum recommended duration of infusion of gemcitabine was
      12 hours (7,200 mg/m(2)). The mean steady-state concentration of gemcitabine was
      24.72 micromol/L and varied over a fivefold range among patients. Overall
      response rates in this phase I trial for strata I and II were 42% and 63%,
      respectively. CONCLUSION: Prolonged-infusion gemcitabine at a fixed dose rate of
      10 mg/m(2)/min for 12 hours with 12 mg/m(2)/d mitoxantrone for 3 days is a
      tolerable induction regimen and achieves plasma concentrations sufficient for
      maximal intracellular activation. Stomatitis or esophagitis should be
      anticipated; however, this regimen may induce significant responses in patients
      with difficult-to-treat leukemias.

PMID- 11821448
TI  - Tumor hypoxia has independent predictor impact only in patients with node
      negative cervix cancer.
AB  - PURPOSE: This prospective clinical study was begun in 1994 to validate the
      independent prognostic impact of tumor hypoxia in patients with cervix cancer
      treated with definitive radiation therapy. PATIENTS AND METHODS: Between May 1994
      and January 1999, 106 eligible patients with epithelial cervix cancer had tumor
      oxygen pressure (PO(2)) measured using the Eppendorf probe. Oxygenation data are
      presented as the hypoxic proportion, defined as the percentage of PO(2) readings
      less than 5 mm/Hg (abbreviated as HP(5)) and the median PO(2). RESULTS: The
      median HP(5) in individual patients was 48%, and the median PO(2) was HP(5).
      Progression-free survival (PFS) for patients with hypoxic tumors (HP(5) > 50%)
      was 37% at 3 years versus 67% in those patients with better oxygenated tumors (P
      =.004). In multivariate analysis, only tumor size (risk ratio [RR], 1.33; P
      =.0003) and evidence of pelvic nodal metastases on imaging studies (RR, 2.52; P
      =.0065) were predictive of PFS. However, an interaction between nodal status and
      oxygenation was observed (P =.006), and further analysis indicated that HP(5) was
      an independent predictor of outcome in patients with negative nodes on imaging (P
      =.007). There was a significant increase in the 3-year cumulative incidence of
      distant metastases in the hypoxic group (41% v 15% in those with HP(5) < 50%; P
      =.0023), but not in pelvic relapse (37% v 27%; P =.12). CONCLUSION: Tumor hypoxia
      is an independent predictor of poor PFS only in patients with node-negative
      cervix cancer, in addition to tumor size. Its impact appears to be related to an
      increased risk of distant metastases rather than to an effect on pelvic control.

PMID- 11821449
TI  - Lymphatic mapping and sentinel node identification in patients with cervix cancer
      undergoing radical hysterectomy and pelvic lymphadenectomy.
AB  - PURPOSE: The purpose of this study was to determine the feasibility of sentinel
      node identification in patients with invasive cervix cancer undergoing radical
      hysterectomy and pelvic lymphadenectomy using preoperative and intraoperative
      lymphatic mapping. PATIENTS AND METHODS: Thirty-nine patients at two institutions
      were enrolled onto this institutional review board-approved study. All underwent
      preoperative lymphoscintigraphy and intraoperative lymphatic mapping with blue
      dye and a handheld gamma probe. Radical hysterectomy was aborted in four patients
      because metastatic disease was discovered on frozen section analysis of the
      sentinel node. RESULTS: Preoperative lymphoscintigraphy revealed at least one
      sentinel node in 33 patients (85%), including 21 (55%) with bilateral sentinel
      nodes. All 39 patients had at least one sentinel node identified
      intraoperatively. Eighty percent of sentinel nodes were in three pelvic
      locations: iliac, obturator, and parametrial (in descending order of frequency).
      The remaining sentinel nodes were in the common iliac and para-aortic nodal
      basins. A total of 132 nodes were identified clinically as sentinel nodes; 65
      (49%) were both blue and hot, 35 (27%) were blue only, and 32 (24%) were hot
      only. Eight patients (21%) had metastatic disease. In five of these patients,
      sentinel nodes were the only positive lymph nodes. One patient had false-negative
      sentinel nodes. She had four microscopically positive parametrial nodes that were
      resected in continuity with the uterus. The sensitivity of the sentinel node was
      87.5% and the negative predictive value was 97%. CONCLUSION: Preoperative
      lymphoscintigraphy and intraoperative lymphatic mapping were highly successful at
      identifying sentinel nodes in patients undergoing radical hysterectomy.

PMID- 11821450
TI  - Intraperitoneal chemotherapy for ovarian carcinoma: results of long-term follow
      up.
AB  - PURPOSE: To determine long-term survival and predictors of recurrence in a
      retrospective cohort of patients with epithelial ovarian cancer treated with
      intraperitoneal (IP) chemotherapy. PATIENTS AND METHODS: Records were reviewed of
      433 patients who received IP therapy for ovarian cancer between 1984 and 1998;
      follow-up data were available for 411 patients. IP therapy was provided as
      consolidation therapy (n = 89), or for treatment of persistent (n = 310) or
      recurrent (n = 12) disease after surgery and initial systemic therapy; therapy
      usually consisted of platinum-based combination therapy. Statistical analysis
      included tests for associations between potential prognostic factors, and between
      prognostic factors and survival. Survival probabilities were estimated by Kaplan
      Meier methods, and prognostic factors for survival were evaluated by a Cox
      proportional hazard model. RESULTS: The mean age of patients was 52 years (range,
      25 to 76 years). Distribution by stage and grade was as follows: stage I, 7; II,
      24; III, 342; IV, 52; not available (NA), 8; and grade 1, 30; 2, 99; and 3, 289;
      NA, 15. The median survival from initiation of IP therapy by residual disease was
      none, 8.7 years; microscopic, 4.8 years; less than 1 cm, 3.3 years; more than 1
      cm, 1.2 years. In a multivariate analysis, the only significant predictors of
      long-term survival were grade and size of residual disease at initiation of IP
      therapy. CONCLUSION: Prolonged survival was observed in selected patients
      receiving IP platinum-based therapy. It is not possible to determine the
      contribution of IP therapy to survival in this study. A relationship between size
      of disease at the initiation of IP therapy and long-term survival was
      demonstrated.

PMID- 11821451
TI  - Does menopausal hormone replacement therapy interact with known factors to
      increase risk of breast cancer?
AB  - PURPOSE: We and other investigators have previously shown that postmenopausal
      combined estrogen and progestin replacement therapy (EPRT) increases the risk of
      breast cancer and that the risk associated with EPRT is substantially higher than
      for estrogen replacement therapy (ERT) alone. The present study was conducted to
      determine whether any particular subgroup of women are at particularly high risk
      of breast cancer if they use EPRT and whether tumor characteristics in women who
      develop cancer while on ERT or EPRT are different from those in women not using
      ERT or EPRT. PATIENTS AND METHODS: We conducted a population-based case-control
      study in Los Angeles, CA, with patients diagnosed with breast cancer in the late
      1980s and early 1990s. Control subjects were matched to patients on age,
      ethnicity, and neighborhood of residence. We present data on 1,897 postmenopausal
      patients and 1,637 controls aged 55 to 72 years who had not undergone a simple
      hysterectomy. RESULTS: Relative risk of breast cancer associated with EPRT use
      did not vary with body mass index (body mass index at or below v above median
      [24.6 kg/m(2)]; P =.98), alcohol intake (> or + one v < one drink per week; P
      =.16), parity (nulliparous v parous; P =.45), history of benign breast disease
      (yes v no; P =.99), or family history of breast cancer (first degree v none; P
      =.57). All of these results were compatible with our previously reported estimate
      of an increased risk of breast cancer of 5% per year of use of EPRT. Hormone
      users, principally EPRT users, were more likely to have hormone receptor-
      positive, especially progesterone-positive, tumors. CONCLUSION: We found no
      evidence that the risk of breast cancer associated with EPRT is limited to
      subgroups of women with specific cofactors. Tumors in EPRT users are more often
      hormone receptor--positive, indicating that they may have a better prognosis than
      breast cancer overall.

PMID- 11821452
TI  - Prognostic model for relapse after high-dose chemotherapy with autologous stem
      cell transplantation for stage IV oligometastatic breast cancer.
AB  - PURPOSE: To study prognostic factors after high-dose chemotherapy (HDC) for
      patients with stage IV oligometastatic breast cancer. PATIENTS AND METHODS: Sixty
      patients with minimal metastatic disease amenable to local therapy enrolled onto
      a prospective HDC trial were analyzed for potential prognostic factors. Tumor
      blocks were retrospectively collected from referring institutions. RESULTS:
      Median follow-up was 62 months (range, 4 to 120 months). Median relapse-free
      survival (RFS) and overall survival (OS) times were 52 and 80 months,
      respectively. Five-year RFS and OS rates were 52% (95% confidence interval [CI],
      39% to 64%) and 62% (95% CI, 49% to 74%), respectively. HER-2 expression, number
      of tumor sites, primary axillary nodal ratio (number of positive nodes divided by
      number of sampled nodes), number of positive axillary nodes, and delivery or
      omission of radiotherapy to metastases correlated with RFS. HER-2 overexpression
      and more than one site were independent adverse risk factors for RFS. HER-2 and
      the axillary nodal ratio were independent predictors of OS. The following
      prognostic categories for RFS were established (RFS rate, median RFS): good risk,
      no factors (77%, 80 months); intermediate risk, one factor (41%, 28 months); and
      poor risk, both factors (10%, 10 months). CONCLUSION: Long-term results in
      patients with oligometastatic breast cancer are encouraging but need validation
      in prospective randomized studies. HER-2 expression, number of sites, and primary
      nodal ratio are independent outcome predictors. Confirmation of these
      observations in this selected population would imply the need for reevaluation of
      the current tenet that early detection of metastatic breast cancer recurrence is
      of no benefit.

PMID- 11821453
TI  - Efficacy and safety of trastuzumab as a single agent in first-line treatment of
      HER2-overexpressing metastatic breast cancer.
AB  - PURPOSE: To evaluate the efficacy and safety of first-line, single-agent
      trastuzumab in women with HER2-overexpressing metastatic breast cancer. PATIENTS
      AND METHODS: One hundred fourteen women with HER2-overexpressing metastatic
      breast cancer were randomized to receive first-line treatment with trastuzumab 4
      mg/kg loading dose, followed by 2 mg/kg weekly, or a higher 8 mg/kg loading dose,
      followed by 4 mg/kg weekly. RESULTS: The objective response rate was 26% (95%
      confidence interval [CI], 18.2% to 34.4%), with seven complete and 23 partial
      responses. Response rates in 111 assessable patients with 3+ and 2+ HER2
      overexpression by immunohistochemistry (IHC) were 35% (95% CI, 24.4% to 44.7%)
      and none (95% CI, 0% to 15.5%), respectively. The clinical benefit rates in
      assessable patients with 3+ and 2+ HER2 overexpression were 48% and 7%,
      respectively. The response rates in 108 assessable patients with and without HER2
      gene amplification by fluorescence in situ hybridization (FISH) analysis were 34%
      (95% CI, 23.9% to 45.7%) and 7% (95% CI, 0.8% to 22.8%), respectively. Seventeen
      (57%) of 30 patients with an objective response and 22 (51%) of 43 patients with
      clinical benefit had not experienced disease progression at follow-up at 12
      months or later. The most common treatment-related adverse events were chills
      (25% of patients), asthenia (23%), fever (22%), pain (18%), and nausea (14%).
      Cardiac dysfunction occurred in two patients (2%); both had histories of cardiac
      disease and did not require additional intervention after discontinuation of
      trastuzumab. There was no clear evidence of a dose-response relationship for
      response, survival, or adverse events. CONCLUSION: Single-agent trastuzumab is
      active and well tolerated as first-line treatment of women with metastatic breast
      cancer with HER2 3+ overexpression by IHC or gene amplification by FISH.

PMID- 11821454
TI  - Blinded, randomized, multicenter study to evaluate single administration
      pegfilgrastim once per cycle versus daily filgrastim as an adjunct to
      chemotherapy in patients with high-risk stage II or stage III/IV breast cancer.
AB  - PURPOSE: This multicenter, randomized, double-blind, active-control study was
      designed to determine whether a single subcutaneous injection of pegfilgrastim
      (SD/01, sustained-duration filgrastim; 100 microg/kg) is as safe and effective as
      daily filgrastim (5 microg/kg/d) for reducing neutropenia in patients who
      received four cycles of myelosuppressive chemotherapy. PATIENTS AND METHODS:
      Sixty-two centers enrolled 310 patients who received chemotherapy with docetaxel
      75 mg/m(2) and doxorubicin 60 mg/m(2) on day 1 of each cycle for a maximum of
      four cycles. Patients were randomized to receive on day 2 either a single
      subcutaneous injection of pegfilgrastim 100 microg/kg per chemotherapy cycle (154
      patients) or daily subcutaneous injections of filgrastim 5 microg/kg/d (156
      patients). Absolute neutrophil count (ANC), duration of grade 4 neutropenia, and
      safety parameters were monitored. RESULTS: One dose of pegfilgrastim per
      chemotherapy cycle was comparable to daily subcutaneous injections of filgrastim
      with regard to all efficacy end points, including the duration of severe
      neutropenia and the depth of ANC nadir in all cycles. Febrile neutropenia across
      all cycles occurred less often in patients who received pegfilgrastim. The
      difference in the mean duration of severe neutropenia between the pegfilgrastim
      and filgrastim treatment groups was less than 1 day. Pegfilgrastim was safe and
      well tolerated, and it was similar to filgrastim. Adverse event profiles in the
      pegfilgrastim and filgrastim groups were similar. CONCLUSION: A single injection
      of pegfilgrastim 100 microg/kg per cycle was as safe and effective as daily
      injections of filgrastim 5 microg/kg/d in reducing neutropenia and its
      complications in patients who received four cycles of doxorubicin 60 mg/m(2) and
      docetaxel 75 mg/m(2).

PMID- 11821455
TI  - Association of angiogenesis and disease outcome in node-positive breast cancer
      patients treated with adjuvant cyclophosphamide, doxorubicin, and fluorouracil: a
      Cancer and Leukemia Group B correlative science study from protocols 8541/8869.
AB  - PURPOSE: Increased microvessel density (MVD), a reflection of tumor angiogenesis,
      is associated with diminished relapse-free and overall survival (OS) in several
      subsets of breast cancer patients. However, the utility of this assay in node
      positive patients treated with adjuvant cyclophosphamide, doxorubicin, and
      fluorouracil (CAF) has not been well studied. PATIENTS AND METHODS:
      Immunostaining for factor VIII-related antigen was performed on tissue sections
      from a subset of node-positive patients who received one of three dose/schedule
      regimens of CAF during participation in Cancer and Leukemia Group B protocol
      8541. Sections from 577 cancers exhibited acceptable tumor and immunostaining
      quality and were included in the study. Each section was examined quantitatively
      for MVD as well as non-quantitatively by scoring the presence or absence of a
      prominent vascular pattern. RESULTS: MVD counts were not associated with relapse
      free or OS in univariate analysis. The presence of a prominent plexiform vascular
      pattern was correlated with decreased OS (P =.0085) in univariate analysis, but
      this pattern was not an independent prognostic indicator of survival in
      multivariate analysis. No apparent clinically important interactions between
      measures of angiogenesis, other prognostic factors, administration of tamoxifen,
      and chemotherapy dose were observed. CONCLUSION: Assessment of angiogenesis does
      not provide useful information regarding prognosis in node-positive breast cancer
      patients treated with adjuvant CAF, nor do these measures predict which patients
      will benefit from dose intensification or addition of tamoxifen.

PMID- 11821456
TI  - High-dose versus standard chemotherapy in metastatic breast cancer: comparison of
      Cancer and Leukemia Group B trials with data from the Autologous Blood and Marrow
      Transplant Registry.
AB  - PURPOSE: To assess survival of patients with metastatic breast cancer treated
      with high-dose chemotherapy (HDC) versus standard-dose chemotherapy (SDC).
      PATIENTS AND METHODS: SDC in four Cancer and Leukemia Group B (CALGB) trials was
      compared with hematopoietic stem-cell support in patients from the Autologous
      Blood and Marrow Transplant Registry. Cox proportional hazard regression
      incorporated potentially confounding effects. A total of 1,509 women were
      enrolled onto CALGB trials, and 1,188 women received HDC. No significant survival
      differences existed by CALGB trial or HDC regimen. Consideration was restricted
      to candidates for both SDC and HDC. The resulting sample included 635 SDC and 441
      HDC patients. The outcome of interest was overall survival. RESULTS: The HDC
      group displayed better performance status. The SDC group had slightly better
      survival in first year after treatment. The HDC group had lower hazard of death
      from years 1 to 4 and had somewhat higher probability of 5-year survival
      (adjusted probabilities [95% confidence intervals], 23% [17% to 29%] v 15% [11%
      to 19%], P =.03). CONCLUSION: After controlling for known prognostic factors in
      this nonrandomized analysis of two large independent data sets, women receiving
      HDC versus SDC for metastatic breast cancer have a similar short-term probability
      of survival, and might have a modestly higher long-term probability of survival.

PMID- 11821457
TI  - Influence of letrozole and anastrozole on total body aromatization and plasma
      estrogen levels in postmenopausal breast cancer patients evaluated in a
      randomized, cross-over study.
AB  - PURPOSE: To compare the effects of the two novel, potent, nonsteroidal aromatase
      inhibitors anastrozole and letrozole on total-body aromatization and plasma
      estrogen levels. PATIENTS AND METHODS: Twelve postmenopausal women with estrogen
      receptor-positive, metastatic breast cancer were treated with anastrozole 1 mg
      orally (PO) and letrozole 2.5 mg PO once daily, each given for a time interval of
      6 weeks in a randomized sequence. Total-body aromatization was determined before
      treatment and at the end of each treatment period using a dual-label isotopic
      technique involving isolation of the metabolites with high-performance liquid
      chromatography. Plasma levels of estrone (E(1)), estradiol (E(2)), and estrone
      sulfate (E(1)S) were determined in samples obtained before each injection using
      highly sensitive radioimmunoassays. RESULTS: Pretreatment aromatase levels ranged
      from 1.68% to 4.27%. On-treatment levels of aromatase were detectable in 11 of 12
      patients during treatment with anastrozole (mean percentage inhibition in the
      whole group, 97.3%) but in none of the 12 patients during treatment with
      letrozole (> 99.1% suppression in all patients; Wilcoxon, P =.0022, comparing the
      two drug regimens). Treatment with anastrozole suppressed plasma levels of E(1),
      E(2), and E(1)S by a mean of 81.0%, 84.9%, and 93.5%, respectively, whereas
      treatment with letrozole caused a corresponding decrease of 84.3%, 87.8% and
      98.0%, respectively. The suppression of E(1) and E(1)S was found to be
      significantly better during treatment with letrozole compared with anastrozole (P
      =.019 and.0037, respectively). CONCLUSION: This study revealed letrozole (2.5 mg
      once daily) to be a more potent suppressor of total-body aromatization and plasma
      estrogen levels compared with anastrozole (1 mg once daily) in postmenopausal
      women with metastatic breast cancer.

PMID- 11821458
TI  - Practices and attitudes of Japanese oncologists and palliative care physicians
      concerning terminal sedation: a nationwide survey.
AB  - PURPOSE: To clarify the frequency of practice of sedation therapy for terminally
      ill cancer patients and to identify physicians' attitudes toward sedation.
      METHODS: Questionnaires were mailed to 1,436 Japanese oncologists and palliative
      care physicians with a request to report their practice of and attitudes toward
      palliative sedation therapy. RESULTS: A total of 697 physicians returned
      questionnaires (response rate, 49.6%). Use of mild, intermittent-deep, or
      continuous-deep sedation for physical and psychologic distress was reported by
      89% and 64%, 70% and 46%, and 66% and 38%, respectively. In vignettes in which
      physicians were asked whether they would use sedation for a patient with
      refractory dyspnea or with existential distress, 14% and 15%, respectively, chose
      continuous-deep sedation as a strong possibility. Those physicians less confident
      with psychologic care and with higher levels of professional burnout were more
      likely to choose continuous-deep sedation. In vignettes in which they were asked
      whether they use sedation for a patient with depression or delirium, 39% and 31%,
      respectively, considered psychiatric treatment to be a strong possibility, and
      42% and 50% regarded continuous-deep sedation as a potential treatment option.
      Physicians less involved in caring for the terminally ill and less specialized in
      palliative medicine were significantly less likely to choose psychiatric
      treatment. CONCLUSION: Sedation is frequently used for severe physical and
      psychologic distress of cancer patients. Physicians' clinical experiences with
      the terminally ill and their levels of professional burnout influence the
      decisions. Training and education for physicians in regard to end-of-life care
      and valid clinical guidelines for palliative sedation therapy are necessary.

PMID- 11821459
TI  - Can communication skills training alter physicians' beliefs and behavior in
      clinics?
AB  - PURPOSE: To measure the psychosocial attitudes and beliefs of physicians working
      within oncology in the United Kingdom and to examine whether beliefs alter after
      communication skills training. Additionally, to investigate whether physicians'
      attitudes are reflected in communication behaviors with patients during
      interviews. METHODS: Ninety-three physicians completed a 32-item Physician
      Psychosocial Belief (PPSB) questionnaire at baseline (T1) before randomization to
      attendance at a 3-day residential communication skills course (n = 48) or a
      control group (n = 45). Three months later (T2), both groups completed another
      PPSB and a self-assessment questionnaire recording perceived changes in
      communication with patients. At both time points, physicians' consultations with
      two consenting patients were videotaped. Communication behaviors were measured
      using the Medical Interaction Processing System. RESULTS: Physicians who attended
      the course showed significantly improved attitudes and beliefs toward
      psychosocial issues compared with controls (P =.002). This improvement was
      reflected in the analysis of the videotaped recordings of their communication
      behaviors with patients. Expressions of empathy were more likely for the course
      group at T2 than the controls (P =.02), as were open questions (P =.001),
      appropriate responses to patient cues (P =.005), and psychosocial probing (P
      =.041). These objective findings were supported by physicians' self report of
      changes in communication style during interviews with patients. CONCLUSION: Our
      results show that a communication skills training intervention using behavioral,
      cognitive, and affective components not only increases potentially beneficial and
      more effective interviewing styles but can also alter attitudes and beliefs, thus
      increasing the likelihood that such skills will be used in the clinical setting.

PMID- 11821460
TI  - Comprehensive assessment of the elderly cancer patient: the feasibility of self
      report methodology.
AB  - PURPOSE: Comprehensive geriatric assessment (CGA) has aided the medical community
      greatly in understanding the quality-of-life issues and functional needs of older
      patients. With its professional team assessment approach, however, CGA may be
      time consuming and costly. The goal of the present study was to assess the
      ability of cancer patients to complete a self-administered CGA and then to
      characterize cancer patients across multiple domains and age groups. PATIENTS AND
      METHODS: Two hundred sixty-six male outpatient oncology patients at the Durham
      Veterans Affairs Medical Center were asked to fill out a survey assessing 10
      domains (demographics, comorbid conditions, activities of daily living,
      functional status, pain, financial well being, social support, emotional state,
      spiritual well-being, and quality of life). RESULTS: Seventy-six percent of the
      patients who received their surveys and kept their appointments returned the
      assessment tool. Older oncology patients had significantly less education (P
      <.0001), income (P =.05), frequent exercise (P =.01), and chance of being disease
      free (P =.003) than younger patients. Other findings in older patients were a
      higher rate of marriage (P =.02), more difficulty in taking medications (P =.05),
      and less cigarette (P =.03) and alcohol (P =.03) use. Members of all age cohorts
      reported a sense of social support, with younger patients deriving this more from
      family and friends than older patients, and older patients deriving social
      support more from membership in religious communities than younger patients. No
      differences were found across age groups for number and impact of comorbid
      illnesses, number of medications, basic and instrumental activities of daily
      living, pain, overall health rating, financial adequacy, anxiety, depression, and
      quality of life. CONCLUSION: CGA can be conducted in an outpatient cancer
      community using a self-report format. Despite the fact that this population
      varied demographically across age groups and is limited to veterans, this study
      demonstrated remarkable similarities between younger and older cancer patients in
      terms of functional status, health states, and quality of life.

PMID- 11821462
TI  - Postoperative nomogram for 12-year sarcoma-specific death.
AB  - PURPOSE: Few published studies have analyzed risk factors for sarcoma-specific
      death. We developed and internally validated a nomogram that combines the factors
      to predict the probability of 12-year sarcoma-specific death using a database of
      2,136 prospectively followed adult patients treated at a single institution.
      PATIENTS AND METHODS: Nomogram predictor variables included age at diagnosis,
      tumor size (< or = 5, 5 to 10, or > 10 cm), histologic grade (high or low),
      histologic subtype (fibrosarcoma, leiomyosarcoma, liposarcoma, malignant fibrous
      histiocytoma, malignant peripheral nerve tumor, synovial, or other), depth
      (superficial or deep), and site (upper extremity, lower extremity, visceral,
      thoracic or trunk, retrointraabdominal, or head or neck). Death from sarcoma or
      treatment complication was the predicted end point. Three prediction methods were
      compared, Kaplan-Meier analysis of all possible subsets, recursive partitioning,
      and Cox proportional hazards regression analysis. The concordance index was used
      as an accuracy measure with bootstrapping to correct for optimistic bias.
      RESULTS: Sarcoma-specific death at 12 years was 36% (95% confidence interval, 33%
      to 39%). The bootstrap-corrected concordance indices were as follows: Kaplan
      Meier, 0.69; recursive partitioning, 0.74; and Cox regression, 0.77. A nomogram
      was drawn on the basis of the Cox regression model. This nomogram was internally
      validated using bootstrapping and shown to have excellent calibration.
      CONCLUSION: A nomogram has been developed to predict 12-year sarcoma-specific
      death. This tool may be useful for patient counseling, follow-up scheduling, and
      clinical trial eligibility determination.

PMID- 11821461
TI  - Prognostic factors in high-grade osteosarcoma of the extremities or trunk: an
      analysis of 1,702 patients treated on neoadjuvant cooperative osteosarcoma study
      group protocols.
AB  - PURPOSE: To define prognostic factors for response and long-term outcome for a
      wide spectrum of osteosarcomas, extending well beyond those of the typical young
      patient with seemingly localized extremity disease. PATIENTS AND METHODS: A total
      of 1,702 consecutive newly diagnosed patients with high-grade osteosarcoma of the
      trunk or limbs registered into the neoadjuvant studies of the Cooperative
      Osteosarcoma Study Group before July 1998 were entered into an analysis of
      demographic, tumor-related, and treatment-related variables, response, and
      survival. The intended therapeutic strategy included preoperative and
      postoperative chemotherapy with multiple agents as well as surgery of all
      operable lesions. RESULTS: Axial tumor site, male sex, and a long history of
      symptoms were associated with poor response to chemotherapy in univariate and
      multivariate analysis. Actuarial 10-year overall and event-free survival rates
      were 59.8% and 48.9%. Among the variables assessable at diagnosis, patient age
      (actuarial 10-year survival > or = 40, 41.6%; < 40, 60.2%; P =.012), tumor site
      (axial, 29.2%; limb, 61.7%; P <.0001), and primary metastases (yes, 26.7%; no,
      64.4%; P <.0001), and for extremity osteosarcomas, also size (> or = one third,
      52.5%; < one third, 66.7%; P <.0001) and location within the limb (proximal,
      49.3%; other, 63.9%; P <.0001), had significant influence on outcome. Two
      additional important prognostic factors were treatment related: response to
      chemotherapy (poor, 47.2%; good, 73.4%; P <.0001) and the extent of surgery
      (incomplete, 14.6%; macroscopically complete, 64.8%; P <.0001). All factors
      except age maintained their significance in multivariate testing, with surgical
      remission and histologic response emerging as the key prognostic factors.
      CONCLUSION: Tumor site and size, primary metastases, response to chemotherapy,
      and surgical remission are of independent prognostic value in osteosarcoma.

PMID- 11821463
TI  - Phase II study of twice-daily high-dose thoracic radiotherapy alternating with
      cisplatin and vindesine for unresectable stage III non-small-cell lung cancer:
      Japan Clinical Oncology Group Study 9306.
AB  - PURPOSE: To evaluate the efficacy and toxicity of high-dose thoracic radiotherapy
      (TRT) alternating with chemotherapy (CH) for unresectable stage III non--small
      cell lung cancer (NSCLC). PATIENTS AND METHODS: Forty-one patients received TRT
      with 1.5 Gy twice daily, 5 days a week, on weeks 1, 2, 5, 6, and 9, up to a total
      dose of 66 to 72 Gy, alternating with cisplatin 80 mg/m(2) on day 1 and vindesine
      3 mg/m(2) on days 1 and 8, repeated every 4 weeks, for two or three courses
      beginning on week 3. RESULTS: The median (range) total dose of TRT and number of
      CH courses were 72 Gy (16.5 to 72 Gy) and three (zero to three), respectively.
      Delay in TRT > or = 5 days was observed in 24 (75%) of 32 patients who completed
      the projected treatment, due to leukopenia in 12, esophagitis in seven, infection
      in two, and other causes in three patients. Partial responses were obtained in 36
      patients (88%). The median survival time and 3- and 5-year survival rates were
      18.4 months, 24%, and 10%, respectively. Grade 3 or 4 leukopenia and esophagitis
      developed in 32 and seven patients, respectively. Grade 3 or 4 late esophageal
      toxicity developed in two patients. CONCLUSION: Alternating high-dose TRT and CH
      for stage III NSCLC produced a high response rate with median and long-term
      survival comparable to prior trials utilizing standard approaches in this
      population. Acute and late esophageal toxicity was observed and interruption of
      TRT was required in most of the patients.

PMID- 11821464
TI  - Phase I trial of weekly gemcitabine and concurrent radiotherapy in patients with
      inoperable non-small-cell lung cancer.
AB  - PURPOSE: To report the evidence of a phase I trial planned to determine the
      maximum-tolerated dose (MTD) and related toxicity of weekly gemcitabine (GEM) and
      concurrent radiotherapy in patients with non--small-cell lung cancer (NSCLC). In
      addition, the response to treatment was evaluated and reported. PATIENTS AND
      METHODS: Thirty-six patients with histologically confirmed NSCLC deemed
      unresectable because of advanced stage were observed and treated according to a
      combined chemoradiation protocol with GEM as chemotherapeutic agent. GEM was
      given weekly for 5 consecutive weeks as a 30-minute intravenous infusion
      concurrent with radiotherapy (1.8 Gy/d; total dose, 50.4 Gy). The initial dose
      was 100 mg/m(2). Pulmonary, esophageal, cardiac, hematologic, and skin toxicities
      were assessed. The dose of GEM was increased by 50 mg/m(2) up to a dose of 250
      mg/m(2); an additional increase by 25 mg/m(2) up to the MTD was planned and
      realized. Three patients were enrolled for each dose level. RESULTS: Dose
      limiting toxicity was identified for the 375-mg/m(2) level with two episodes of
      grade 2 esophagitis and two of grade 3 pulmonary actinic interstitial disease.
      The weekly dose of GEM 350 mg/m(2) was well tolerated. CONCLUSION: A weekly GEM
      dose of 350 mg/m(2) concurrent with radiotherapy was well tolerated. Promising
      results regarding response to treatment were observed and reported.

PMID- 11821465
TI  - Bax expression decreases significantly from primary tumor to metastasis in
      colorectal cancer.
AB  - PURPOSE: Bax is a proapoptotic member of the bcl-2 family. Previous studies about
      Bax have shown that the expression increases from normal to tumor tissue, but the
      clinical significance is contradictory. Our aims were to analyze the expression
      of Bax from normal mucosa to primary tumor and to metastases in colorectal cancer
      patient. We further investigated whether low Bax expression in the primary tumor
      or changed expression from normal mucosa to primary tumor and to metastases had
      biologic and clinical significance. PATIENTS AND METHODS: The study included 135
      patients with primary colorectal adenocarcinoma, of whom 31 had metastases in the
      lymph nodes and 75 had normal mucosa. Immunohistochemistry, DNA sequencing, and
      microsatellite analysis were used to detect Bax expression, mutations, and
      microsatellite instability. RESULTS: The protein was observed in 132 of 135
      tumors, all normal epithelial cells and metastases. The frequencies of weak
      expression were greater from well/moderately to poorly differentiated and to
      mucinous carcinomas. Bax expression was stronger from normal to tumor tissue, but
      subsequently decreased in metastases. The matched cases with lower expression in
      the metastases than in the primary tumor showed a more infiltrative growth
      pattern and more distal metastases. CONCLUSION: The association of Bax expression
      with tumor differentiation/histologic types and a decreased expression in the
      metastases, suggests that Bax expression may be involved in tumor
      differentiation/histologic types and metastatic progression. We also propose the
      novel notion that changed Bax expression in the metastases compared with the
      primary tumors might provide information to determine the clinicopathologic
      characteristics of the tumor.

PMID- 11821467
TI  - Up-to-date long-term survival curves of patients with cancer by period analysis.
AB  - PURPOSE: Provision of up-to-date long-term survival curves is an important task
      of cancer registries. Traditionally, survival curves have been derived for
      cohorts of patients diagnosed many years ago. Using data of the Finnish Cancer
      Registry, we provide an empirical assessment of the use of a new method of
      survival analysis, denoted period analysis, for deriving more up-to-date survival
      curves. PATIENTS AND METHODS: We calculated 10-year relative survival curves
      actually observed for patients diagnosed with one of the 15 most common forms of
      cancer in 1983 to 1987, and we compared them with the most up-to-date 10-year
      relative survival curves that might have been obtained in 1983 to 1987 using
      either traditional (cohort-wise) or period analysis. We also give the most recent
      10-year survival curves obtained by period analysis for the 1993 to 1997 period.
      RESULTS: For all forms of cancer, period analysis of the 1983 to 1987 data
      yielded survival curves that were very close to the survival curves later
      observed for patients who were newly diagnosed in that period (median and maximum
      difference of 10-year relative survival estimates: 0.9 and 5.7 percent units,
      respectively). By contrast, the survival curves obtained by traditional (cohort
      wise) survival analysis in 1983 to 1987 would have been much lower for most forms
      of cancer (median and maximum difference: 5.8 and 18.4 percent units,
      respectively). The 10-year survival curves for the 1993 to 1997 period are
      substantially more favorable than previously available, traditionally derived
      survival curves for most forms of cancer. CONCLUSION: Period analysis is a useful
      tool for deriving up-to-date long-term survival curves of patients with cancer.

PMID- 11821466
TI  - Acute side effects and complications after short-term preoperative radiotherapy
      combined with total mesorectal excision in primary rectal cancer: report of a
      multicenter randomized trial.
AB  - PURPOSE: Total mesorectal excision (TME) surgery in the treatment of rectal
      cancer has been shown to result in a reduction in the number of local recurrences
      in retrospective studies. Reports on improved local control after preoperative,
      hypofractionated radiotherapy (RT) have led to the introduction of a prospective
      randomized multicenter trial, in which the effect of TME surgery with or without
      preoperative RT were evaluated. Any benefit in regard to a reduced local
      recurrence rate and possible improved survival must be weighed against potential
      adverse effects in both the short-term and the long-term. The present study was
      undertaken to assess the acute side effects of short-term, preoperative RT in
      rectal cancer patients and to study the influence of five doses of 5 Gy on
      surgical parameters, postoperative morbidity and mortality in patients randomized
      in the Dutch TME trial. PATIENTS AND METHODS: We analyzed 1,530 Dutch patients
      entered onto a prospective randomized trial, comparing preoperative RT with five
      doses of 5 Gy followed by TME surgery with TME surgery alone, of which 1,414
      patients were assessable. Toxicity from RT, surgery characteristics, and
      postoperative complications and mortality were compared. RESULTS: Toxicity during
      RT hardly occurred. Irradiated patients had 100 mL more blood loss during the
      operation (P <.001) and showed more perineal complications (P =.008) in cases of
      abdominoperineal resection. The total number of complications was slightly
      increased in the irradiated group (P =.008). No difference was observed in
      postoperative mortality (4.0% v 3.3%) or in the number of reinterventions.
      CONCLUSION: Preoperative hypofractionated RT is a safe procedure in patients
      treated with TME surgery, despite a slight increase in complications when
      compared with TME surgery only.

PMID- 11821468
TI  - Association of preoperative plasma levels of insulin-like growth factor I and
      insulin-like growth factor binding proteins-2 and -3 with prostate cancer
      invasion, progression, and metastasis.
AB  - PURPOSE: We tested the hypothesis that preoperative plasma levels of insulin-like
      growth factor (IGF) binding protein (BP)-2 or IGFBP-3 would predict cancer stage
      and prognosis in patients undergoing radical prostatectomy. MATERIAL AND METHODS:
      Plasma levels of IGF-I, IGFBP-2, and IGFBP-3 were measured preoperatively in 120
      consecutive patients who underwent radical prostatectomy for clinically localized
      disease, postoperatively in 51 of these patients, in 44 healthy men, in 19
      patients with metastases to regional lymph nodes, and in 10 patients with bone
      metastases. RESULTS: Plasma IGFBP-3 levels were lowest in patients with bone
      metastases (P < or = .043). IGFBP-2 levels were elevated in prostate cancer
      patients compared with healthy subjects (P < or = .006). However, within the
      group of prostatectomy patients, preoperative plasma IGFBP-2 levels were lower in
      patients with advanced disease (P < or = .033), were inversely correlated with
      prostatic tumor volume (P =.037), and declined after prostate removal (P =.044).
      Lower preoperative IGFBP-2 and IGFBP-3 levels and biopsy Gleason score were
      independent predictors of biochemical progression (P =.043, P =.040, and P =.020,
      respectively). In patients with disease progression, preoperative plasma IGFBP-3
      levels were lower in those with aggressive than in those with nonaggressive
      failure (P =.042). CONCLUSION: Elevation of plasma IGFBP-2 levels in prostate
      cancer patients apparently is due to increased release directly from the
      prostate. For patients with clinically localized prostate cancer, preoperative
      plasma IGFBP-2 levels are inversely associated with biologically aggressive
      disease and disease progression. Preoperative plasma IGFBP-3 levels were
      decreased in patients with prostate cancer metastases and were an independent
      predictor of biochemical progression after surgery, presumably because of an
      association with occult metastatic disease present at the time of radical
      prostatectomy.

PMID- 11821469
TI  - Role of radiotherapy in the treatment of supratentorial primitive neuroectodermal
      tumors in childhood: results of the prospective German brain tumor trials HIT
      88/89 and 91.
AB  - PURPOSE: To evaluate the outcome of children with supratentorial primitive
      neuroectodermal tumors after surgery, irradiation, and chemotherapy and to
      identify factors predictive for survival. PATIENTS AND METHODS: Sixty-three
      children in the prospective trials HIT 88/89 and HIT 91 were eligible. Complete
      resection was performed in 21 patients. Patients were randomized for
      preirradiation chemotherapy, consisting of two cycles of ifosfamide, etoposide,
      methotrexate, cisplatin, and cytarabine (n = 40), or chemotherapy after
      irradiation, consisting of eight cycles with cisplatin, vincristine, and
      lomustine (n = 23). Irradiation volume was recommended to encompass the neuraxis
      with 35.2-Gy total dose followed by a boost (20.0 Gy) to the primary tumor site
      (n = 54). Seven patients were irradiated to the tumor region only with a total
      dose of 54.0 Gy. RESULTS: Overall survival at 3 years was 48.4%. Progression
      occurred in 38 children, with local recurrences in 27 patients. The only
      significant prognostic factor was dose and volume of radiotherapy (progression
      free survival after 3 years was 49.3% with correct treatment compared with 6.7%
      for 15 children with major violations of radiotherapy). Ten early progressions
      occurred during adjuvant therapy (eight before and two during radiotherapy), nine
      of them treated with preirradiation chemotherapy. There was a positive trend in
      outcome for nonmetastatic and pineal tumors. CONCLUSION: Significant predictive
      factors were dose and volume of radiotherapy. Volume of irradiation should
      encompass the whole CNS with additional boost to the tumor region. Local doses of
      at least 54 Gy and a craniospinal dose of 35 Gy are necessary. Preirradiation
      chemotherapy seems to increase risk of early progression.

PMID- 11821470
TI  - Prospective evaluation of the peptide-bound collagen type I cross-links N
      telopeptide and C-telopeptide in predicting bone metastases status.
AB  - PURPOSE: The objective assessment of bone metastases is currently based on serial
      changes in skeletal survey. We performed a prospective study to determine whether
      a correlation exists between the biochemical markers of bone turnover and x-ray
      evaluation of bone metastases in patients with or without bisphosphonate therapy,
      and whether bone markers are influenced by extraskeletal disease. PATIENTS AND
      METHODS: Patients with either bone or extraskeletal metastases were consecutively
      enrolled and World Health Organization response criteria were applied for both
      bone and extraosseous disease every 3 to 4 months. Serum levels of bone-specific
      alkaline phosphatase (B-AP) and C-telopeptide (ICTP) and urine levels of N
      telopeptide (NTX) were measured monthly. The data were analyzed by generalized
      estimation equation regression. RESULTS: We studied 97 patients with bone
      metastases (52 also with extraskeletal metastases) and 26 with extraosseous
      disease only. Median time on study was 153 days, and 281 objective evaluations
      (171 in bone) were performed. With bisphosphonates (49 patients receiving
      pamidronate and three receiving clodronate), percent change from levels without
      therapy was 47% for NTX (P <.001) and 69% for B-AP (P =.008). With disease
      progression in bone, percent change from mean levels during stable disease was
      152% for NTX (P <.001) and 144% for ICTP (P <.001) regardless of bisphosphonate
      therapy. NTX had the highest positive predictive value (71%) for the diagnosis of
      bone metastases progression. Extraskeletal disease had no significant effect on
      bone markers. CONCLUSION: Urinary NTX may be a valuable bone marker to assess the
      antiresorptive effect of bisphosphonate therapy and to evaluate the progression
      of bone metastases.

PMID- 11821472
TI  - Challenges in oncology. Case 1. Oncology emergencies: a myeloma patient with
      stridor.

PMID- 11821471
TI  - Induction chemotherapy followed by low-dose involved-field radiotherapy for
      intracranial germ cell tumors.
AB  - PURPOSE: To investigate the efficacy of chemotherapy followed by low-dose
      involved-field radiotherapy for the treatment of intracranial germ cell tumors
      (GCTs). PATIENTS AND METHODS: Thirty-three patients with GCTs, including 16 pure
      germinomas, 11 human chorionic gonadotropin-beta (HCG-beta)-secreting germinomas,
      three mixed GCTs composed of immature teratomas plus germinomas (IMT/G), and
      three highly malignant mixed GCTs, were treated. Etoposide and cisplatin (EP)
      were used for the treatment of solitary pure germinomas, and ifosfamide,
      cisplatin, and etoposide (ICE) were used for the treatment of other GCTs. The
      dose schedule was 24 Gy for germinomas and 40 to 54 Gy for other GCTs. An
      involved-field set-up was used except for highly malignant GCTs, in which
      craniospinal irradiation was used. The median follow-up was 58 months (range, 18
      to 102 months). RESULTS: Disease-related, overall, and relapse-free survival
      rates at 5 years were 100%, 93%, and 69% for all patients, 100%, 100%, and 86%
      for patients with pure germinomas, and 100%, 75%, and 44% for patients with HCG
      beta-secreting germinomas, respectively. All six patients with nongerminomatous
      GCTs were alive at the last follow-up. All eight relapses (one pure germinoma,
      five HCG-beta-secreting germinomas, and two IMT/G), except one in a course of
      salvage treatment, were salvaged and free of disease at the last follow-up. No
      decline was observed in the full-scale, verbal, or performance intelligence
      quotient at 12 to 51 months after the treatment in 11 patients. CONCLUSION: Our
      results support an excellent prognosis after EP and ICE regimens followed by
      radiotherapy. Dose and volume can be reduced to 24 Gy in 12 fractions and involve
      a field set-up after EP chemotherapy for the treatment of pure germinomas.

PMID- 11821473
TI  - Challenges in oncology. Case 2. Radiation recall associated with docetaxel.

PMID- 11821474
TI  - Challenges in oncology. Case 3. Depigmentation in a chronic myeloid leukemia
      patient treated with STI-571.

PMID- 11821475
TI  - Challenges in oncology. Case 4. Response of metastatic gastrointestinal stromal
      tumor including CNS involvement to imatinib mesylate (STI-571).

PMID- 11821476
TI  - Why me?

PMID- 11821477
TI  - Superior efficacy of letrozole versus tamoxifen as first-line therapy.

PMID- 11821478
TI  - Clinical evaluation of once-weekly and three-times-weekly dosings of epoetin alfa
      in chemotherapy patients: problems of study design and interpretation.

PMID- 11821479
TI  - Meeting highlights: International Consensus Panel on the treatment of primary
      breast cancer.

PMID- 11821480
TI  - Role of symptom control and palliative care abstract presentations.

PMID- 11821481
TI  - Regression of mucosa-associated lymphoid tissue lymphoma of the bladder after
      antibiotic therapy.

PMID- 11821482
TI  - Is muscle involved in the mechanical adaptability of echinoderm mutable
      collagenous tissue?
AB  - The mutable collagenous tissue (MCT) of echinoderms has the capacity to change
      its mechanical properties in a time scale of less than 1 s to a few minutes under
      the influence of the nervous system. Although accumulating evidence indicates
      that the mechanical adaptability of MCT is due primarily to the modulation of
      interactions between components of the extracellular matrix, the presence of
      muscle in a few mutable collagenous structures has led some workers to suggest
      that contractile cells may play an important role in the phenomenon of variable
      tensility and to call for a re-evaluation of the whole MCT concept. This
      contribution summarises present information on MCT and appraises the argument
      implicating muscle in its unique mechanical behaviour. It is concluded that there
      is no evidence that the variability of the passive mechanical properties of any
      mutable collagenous structure is due to muscle.

PMID- 11821483
TI  - Hyperosmoregulation in the red freshwater crab Dilocarcinus pagei (Brachyura,
      Trichodactylidae): structural and functional asymmetries of the posterior gills.
AB  - The osmotic and ionic status of the haemolymph and the structural and ion
      transport characteristics of the posterior gills of Dilocarcinus pagei, a
      hololimnetic crab, were investigated. Haemolymph osmolality was 386 +/- 18 mosmol
      kg(-1), while [Na(+)] and [Cl(-)] were 190 +/- 13 and 206 +/- 12 mmol l(-1),
      respectively; [K(+)], [Ca(2+)] and [Mg(2+)] were 9.7 +/- 0.7, 10.2 +/- 0.5 and
      2.8 +/- 0.4 mmol l(-1), respectively (means +/- S.E.M., N=12-17). The gill
      lamellae possess a central, osmiophilic area, which exhibits a marked structural
      asymmetry. The thick (18-20 microm) proximal epithelium is characterised by basal
      invaginations and a few apical vesicles, while the thin (3-10 microm) distal
      epithelium consists of apical pillar cell flanges populated by vesicles and
      membrane invaginations. Isolated gills, bathed and perfused with NaCl saline,
      spontaneously generate a negative transbranchial potential difference (V(te)),
      which stabilises at positive or negative values. Ouabain shifts V(te) to more
      positive values. When mounted in an Ussing chamber, distal split lamellae
      generate a negative, Cl(-)-dependent short-circuit current (I(sc)). Na(+)
      substitution leads to more negative values of I(sc). Internal ouabain is without
      effect, while diphenylamine-2-carboxylate and acetazolamide abolish I(sc).
      Proximal split lamellae show a positive, Na(+)-dependent I(sc), which decreases
      after internal application of ouabain. These data suggest that the thin
      epithelium actively absorbs Cl(-), while the thick epithelium actively absorbs
      Na(+).

PMID- 11821484
TI  - Performance limits of labriform propulsion and correlates with fin shape and
      motion.
AB  - Labriform locomotion, which is powered by oscillating the paired pectoral fins,
      varies along a continuum from rowing the fins back and forth to flapping the fins
      up and down. It has generally been assumed (i) that flapping is more mechanically
      efficient than rowing, a hypothesis confirmed by a recent simulation experiment,
      and (ii) that flapping should be associated with wing-shaped fins while rowing
      should be associated with paddle-shaped fins. To determine whether these
      hypotheses and the results of the simulation experiment are consistent with
      natural variation, we compared the steady swimming performance (critical swimming
      speed) of four species of labrid fish (Cirrhilabrus rubripinnis, Pseudocheilinus
      octotaenia, Gomphosus varius and Halichoeres bivittatus) selected to form two
      pairs of closely related species that vary in fin shape and in the direction of
      fin motion. The results were consistent with expectations. Within each pair, the
      species with the best swimming performance also had (i) a fin shape characterized
      by a higher aspect ratio, a longer leading edge relative to the trailing edge fin
      rays and the center of fin area located closer to the fin base, and (ii) a
      steeper (more dorsoventral) stroke plane.

PMID- 11821485
TI  - Effects of longitudinal body position and swimming speed on mechanical power of
      deep red muscle from skipjack tuna (Katsuwonus pelamis).
AB  - The mechanical power output of deep, red muscle from skipjack tuna (Katsuwonus
      pelamis) was studied to investigate (i) whether this muscle generates maximum
      power during cruise swimming, (ii) how the differences in strain experienced by
      red muscle at different axial body locations affect its performance and (iii) how
      swimming speed affects muscle work and power output. Red muscle was isolated from
      approximately mid-way through the deep wedge that lies next to the backbone;
      anterior (0.44 fork lengths, ANT) and posterior (0.70 fork lengths, POST) samples
      were studied. Work and power were measured at 25 degrees C using the work loop
      technique. Stimulus phases and durations and muscle strains (+/- 5.5 % in ANT and
      +/- 8 % in POST locations) experienced during cruise swimming at different speeds
      were obtained from previous studies and used during work loop recordings. In
      addition, stimulus conditions that maximized work were determined. The stimulus
      durations and phases yielding maximum work decreased with increasing cycle
      frequency (analogous to tail-beat frequency), were the same at both axial
      locations and were almost identical to those used by the fish during swimming,
      indicating that the muscle produces near-maximal work under most conditions in
      swimming fish. While muscle in the posterior region undergoes larger strain and
      thus produces more mass-specific power than muscle in the anterior region, when
      the longitudinal distribution of red muscle mass is considered, the anterior
      muscles appear to contribute approximately 40% more total power. Mechanical work
      per length cycle was maximal at a cycle frequency of 2-3 Hz, dropping to near
      zero at 15 Hz and by 20-50% at 1 Hz. Mechanical power was maximal at a cycle
      frequency of 5 Hz, dropping to near zero at 15 Hz. These fish typically cruise
      with tail-beat frequencies of 2.8-5.2 Hz, frequencies at which power from cyclic
      contractions of deep red muscles was 75-100% maximal. At any given frequency over
      this range, power using stimulation conditions recorded from swimming fish
      averaged 93.4 +/- 1.65% at ANT locations and 88.6 +/- 2.08% at POST locations
      (means +/- S.E.M., N=3-6) of the maximum using optimized conditions. When cycle
      frequency was held constant (4 Hz) and strain amplitude was increased, work and
      power increased similarly in muscles from both sample sites; work and power
      increased 2.5-fold when strain was elevated from +/- 2 to +/- 5.5%, but increased
      by only approximately 12% when strain was raised further from +/- 5.5 to +/- 8%.
      Taken together, these data suggest that red muscle fibres along the entire body
      are used in a similar fashion to produce near-maximal mechanical power for
      propulsion during normal cruise swimming. Modelling suggests that the tail-beat
      frequency at which power is maximal (5 Hz) is very close to that used at the
      predicted maximum aerobic swimming speed (5.8 Hz) in these fish.

PMID- 11821486
TI  - Light-induced and circadian changes in the compound eye of the haematophagous bug
      Triatoma infestans (Hemiptera: Reduviidae).
AB  - We analysed dynamic changes in the ommatidial structure of the compound eyes of
      Triatoma infestans. This nocturnal insect possesses open-rhabdom eyes, in which a
      ring of six rhabdomeres from retinula cells 1-6 (R1-6) surrounds a central pair
      of rhabdomeres from retinula cells 7 and 8 (R7-8). Screening pigments are located
      in all the photoreceptors and in the primary (PPC) and secondary (SPC) pigment
      cells. During the day, pigments within R1-6 and the PPCs form a small 'pupil'
      above the rhabdom and pigments within R7-8 are clustered around the central
      rhabdomere, allowing light to reach only the central rhabdomere. At night, the
      'pupil' widens, and pigments inside R7-8 concentrate in the proximal region of
      the cells, allowing light to reach the peripheral rhabdomeres. In addition, the
      distance between the cornea and the rhabdom decreases. These rhythmic changes
      adapt the sensitivity of the eye by controlling the amount of light reaching and
      travelling within the rhabdom. Furthermore, the rhythm persists under conditions
      of constant darkness (DD), i.e. it is controlled by an endogenous oscillator.
      Remarkably, there are differences in pigment movements between the retinula cells
      of a single ommatidium. The migration of pigments in R1-6 is regulated by a
      circadian input, while that in R7-8 is regulated by both direct light and
      circadian inputs. The rhythm vanishes under constant-light conditions (LL). In
      this species, the circadian rhythm of photonegative behaviour persists in both DD
      and LL conditions, suggesting that these two rhythms, in retinal morphology and
      visual behaviour, may be generated by different circadian oscillators.

PMID- 11821487
TI  - In vivo oocyte hydration in Atlantic halibut (Hippoglossus hippoglossus);
      proteolytic liberation of free amino acids, and ion transport, are driving forces
      for osmotic water influx.
AB  - The in vivo swelling and hydration of maturing oocytes of Atlantic halibut
      Hippoglossus hippoglossus were studied in order to characterise the osmotic
      mechanism underlying oocyte hydration in oviparous marine teleosts that spawn
      pelagic eggs. Sequential biopsies from two females, spanning four hydration
      cycles, were examined by osmometry, solute analysis and electrophoresis of
      dissected hydrating oocytes and ovulated eggs. The hydration cycle of the
      biopsied halibuts lasted 33-54 h. The majority of ovarian oocytes existed in a
      pre-hydrated condition (individual wet mass approx. 3.7 mg, diameter approx. 1.87
      mm, 63 % H(2)O) with easily visible, non-coalesced, yolk platelets. Group
      synchronous batches of the pre-hydrated oocytes increased in individual wet mass,
      diameter and water content to reach the ovulated egg stage of approximately 15
      mg, 3.0 mm and 90 % H(2)O, respectively. The yolk osmolality of the hydrating
      oocytes was transiently hyperosmotic to the ovarian fluid (range 305-350 mOsmol
      l(-1)) with a peak osmolality of about 450 mOsmol l(-1) in oocytes of 6-8 mg
      individual wet mass. The transient hyperosmolality was well accounted for by the
      increase in oocyte content of free amino acids (FAAs; approx. 2300 nmol oocyte(
      1)), K(+) (approx. 750 nmol oocyte(-1)), Cl(-) (approx. 900 nmol oocyte(-1)),
      total ammonium (approx. 300 nmol oocyte(-1)) and inorganic phosphate (P(i);
      approx. 200 nmol oocyte(-1)) when relating to the increase in cellular water. The
      oocyte content of Na(+) did not increase during the hydration phase. Extensive
      proteolysis of yolk proteins, in particular a 110 kDa protein, correlated with
      the increase in the FAA pool, although the latter increased by approx. 20 % more
      than could be accounted for by the decrease in the oocyte protein content. Both
      indispensable and dispensable amino acids increased in the FAA pool, and
      particularly serine, alanine, leucine, lysine, glutamine and glutamate. Taurine
      content remained stable at approx. 70 nmol oocyte(-1) during oocyte hydration.
      The results show that final hydration of Atlantic halibut oocytes is caused by an
      osmotic water uptake in which FAAs, derived mainly from the hydrolysis of a 110
      kDa yolk protein, contribute approximately 50 % of the yolk osmolality and ions
      (Cl(-), K(+), P(i), NH(4)(+)) make up the balance.

PMID- 11821488
TI  - Vascular control in larval Xenopus laevis: the role of endothelial-derived
      factors.
AB  - We used novel digital contrasting methods to measure the effects of endothelin-1
      (ET-1, 10(-6) to 10(-8) mol l(-1)), the nitric-oxide-releasing agent sodium
      nitroprusside (SNP, 10(-2) mol l(-1)) and N(omega)-nitro-L-arginine methyl ester
      hydrochloride (L-NAME, 10(-4) mol l(-1)), a non-selective inhibitor of nitric
      oxide synthase, on the diameter of tiny arteries and veins of the head in
      anaesthetized Xenopus laevis tadpoles (stage NF 50-53). Perfusion of the main
      artery and vein supplying the head with ET-1 caused an immediate, significant and
      dose-dependent vasoconstriction. While preincubation with L-NAME caused no
      significant change in vessel diameter, the constriction provoked by subsequent
      endothelin administration was significantly enhanced. Application of SNP caused a
      vasodilation that was significant only after preconstriction with ET-1 (10(-6)
      mol l(-1)). Our results provide strong evidence that the vasculature of
      developing Xenopus laevis tadpoles (NF stage 50-53) is influenced by endogenously
      released nitric oxide and endothelin. Vasoactive mediators released from vascular
      endothelial cells could be particularly important in vascular control in early
      embryos when the autonomic innervation is undifferentiated, poorly developed or
      even absent.

PMID- 11821489
TI  - Effect of menstrual cycle phase on exercise performance of high-altitude native
      women at 3600 m.
AB  - At sea level normally menstruating women show increased ventilation (VE) and
      hemodynamic changes due to increased progesterone (P) and estrogen (E2) levels
      during the mid-luteal (L) compared to the mid-follicular (F) phase of the ovarian
      cycle. Such changes may affect maximal exercise performance. This repeated
      measures, randomized study, conducted at 3600 m, tests the hypothesis that a P
      mediated increase in VE increases maximal oxygen consumption (V(O(2)max)) during
      the L phase relative to the F phase in Bolivian women, either born and raised at
      high altitude (HA), or resident at HA since early childhood. Subjects (N=30)
      enrolled in the study were aged 27.7 +/- 0.7 years (mean +/- S.E.M.) and non
      pregnant, non-lactating, relatively sedentary residents of La Paz, Bolivia, who
      were not using hormonal contraceptives. Mean salivary P levels at the time of the
      exercise tests were 63.3 pg ml(-1) and 22.9 pg ml(-1) for the L and F phases,
      respectively. Subset analyses of submaximal (N=23) and maximal (N=13) exercise
      responses were conducted only with women showing increased P levels from F to L
      and, in the latter case, with those also achieving true (V(O(2)max)). Submaximal
      exercise VE and ventilatory equivalents were higher in the L phase (P<0.001). P
      levels were significantly correlated to the submaximal exercise VE (r=0.487,
      P=0.006). Maximal work output (W) was higher (approximately 5 %) during the L
      phase (P=0.044), but (V(O(2)max)) (l min(-1)) was unchanged (P=0.063). Post-hoc
      analyses revealed no significant relationship between changes in P levels and
      changes in (V(O(2)max))) from F to L (P=0.072). In sum, the menstrual cycle phase
      has relatively modest effects on ventilation, but no effect on (V(O(2)max)) of HA
      native women.

PMID- 11821490
TI  - The effect of stimulus features on the visual orienting behaviour of the
      salamander Plethodon jordani.
AB  - The effects of the visual features of prey-like objects on the orienting
      behaviour of the salamander Plethodon jordani were studied. Two stimuli (cricket
      dummies, rectangles), moving in opposite directions, were presented
      simultaneously on a computer screen. They differed in size, contrast, velocity
      and movement pattern of the entire body or the body appendages. Size and velocity
      appeared to be the dominant features; shape was of lesser importance. Contrast
      and movement pattern were of intermediate importance and local motion of little
      importance. This rank order was the same when the probability of a response to
      the different stimuli was estimated by means of the maximum-likelihood method.
      Cluster analysis revealed that in all animals stimuli could be grouped into five
      clusters. Among individuals, the rank order of stimuli was similar for high- and
      low-ranking stimuli and varied for those of intermediate rank; stimuli could be
      grouped into 3-5 clusters. Our findings favour the view that, in amphibians, prey
      recognition is guided by a number of visual features acting either alone or in
      combination and depending on internal motivational or attentional states and
      individual experience.

PMID- 11821491
TI  - The archaeogastropod mollusc Haliotis iris: tissue and blood metabolites and
      allosteric regulation of haemocyanin function.
AB  - We investigated divalent cation and anaerobic end-product concentrations and the
      interactive effects of these substances and pH on haemocyanin oxygen-binding (Hc
      O(2)) in the New Zealand abalone Haliotis iris. During 24 h of environmental
      hypoxia (emersion), D-lactate and tauropine accumulated in the foot and shell
      adductor muscles and in the haemolymph of the aorta, the pedal sinus and adductor
      muscle lacunae, whereas L-lactate was not detected. Intramuscular and haemolymph
      D-lactate concentrations were similar, but tauropine accumulated to much higher
      levels in muscle tissues. Repeated disturbance and short-term exposure to air
      over 3 h induced no accumulation of D- or L-lactate and no change in [Ca(2+)],
      [Mg(2+)], pH and O(2)-binding properties of the native haemolymph. The haemolymph
      showed a low Hc-O(2) affinity, a large reverse Bohr effect and marked
      cooperativity. Dialysis increased Hc-O(2) affinity, obliterated cooperativity and
      decreased the pH-sensitivity of O(2) binding. Replacing Mg(2+) and Ca(2+)
      restored the native O(2)-binding properties and the reverse Bohr shift. L- and D
      lactate exerted minor modulatory effects on O(2)-affinity. At in vivo
      concentrations of Mg(2+) and Ca(2+), the cooperativity is dependent largely on
      Mg(2+), which modulates the O(2) association equilibrium constants of both the
      high-affinity (K(R)) and the low-affinity (K(T)) states (increasing and
      decreasing, respectively). This allosteric mechanism contrasts with that
      encountered in other haemocyanins and haemoglobins. The functional properties of
      H. iris haemocyanin suggest that high rates of O(2) delivery to the tissues are
      not a priority but are consistent with the provision of a large O(2) reserve for
      facultatively anaerobic tissues during internal hypoxia associated with clamping
      to the substratum.

PMID- 11821492
TI  - Fictive locomotion induced by octopamine in the earthworm.
AB  - We investigated the function of octopamine (OA) as a motor pattern inducer in the
      earthworm Eisenia fetida. We used semi-intact preparations, consisting of 20
      sequential segmental ganglia of the ventral nerve cord (VNC) together with the
      body wall from the middle of the animal. Bath-application of 10(-4) mol l(-1) OA
      to the semi-intact preparation induced phasic muscle contractions, which are
      consistent with crawling. In the isolated VNC, OA induced bursts of motor neuron
      activity in the first lateral nerves. Burst frequency increased with OA
      concentration, with a large increase in activity observed in the range 10(-6)-10(
      4) mol l(-1). At 10(-4) mol l(-1), the coefficient of variation of burst periods
      (BPs) was smaller than that seen upon application of OA at other concentrations,
      which is indicative of rhythmic bursts. These rhythmic bursts propagated along
      the VNC from the anterior to posterior, with a propagation velocity ranging from
      60 to 110 mm s(-1). This velocity is consistent with the propagation velocity of
      muscle contraction during crawling behavior in the intact earthworm. From these
      results, we conclude that fictive crawling motor patterns are observed at 10(-4)
      mol l(-1) OA, and that OA can induce rhythmic bursts in the isolated VNC of the
      earthworm.

PMID- 11821493
TI  - Whole-body hyperthermia-induced thermotolerance is associated with the induction
      of heat shock protein 70 in mice.
AB  - Molecular mechanisms of whole-body thermotolerance (WBT) in mammals have not been
      investigated thoroughly. The purpose of this study was to assess the induction of
      the 70 kDa heat shock protein (HSP70) and antioxidant enzyme activity in animal
      WBT, which was induced by whole-body hyperthermia (WBH) in mice. As a
      preconditioning treatment, WBH was applied to mice to induce WBT. Synthesis of
      inducible HSP70 (HSP70i) and quantification of its increased level in liver were
      investigated by one- and two-dimensional polyacrylamide gel electrophoresis and
      immunoblotting. HSP70i synthesis in mice liver was induced by non-lethal WBH (41
      degrees C, 30 min). When compared to control animals, the level of liver HSP70i
      increased substantially (by 3.6-fold; P<0.0001). When exposed to 30 min of
      hyperthermia preconditioning, and after recovery for 48 h, the survival rate was
      88.2 %, which was significantly higher than that of the control group (37.5 %;
      P<0.01). Moreover, the survival rate of animals subjected to preconditioning for
      15 min was 72.2 %, which was also significantly higher than that of the control
      group (P<0.05). In contrast, the survival rate of animals subjected to
      preconditioning for 45 min was 63.5 %, which was not different from the control
      group. Nonetheless, the protection index of the group subjected to 15 min and 30
      min of preconditioning was 1.93 and 2.37, respectively. Furthermore, to assess
      their contributions to WBT, the activities of antioxidant enzymes were also
      measured. After 48 h of recovery in preconditioned animals, hepatic antioxidant
      enzyme activities, including superoxide dismutase, catalase and glutathione
      peroxidase, had not changed significantly. To study the molecular mechanism of
      WBT, we successfully developed a mouse model and suggest that, rather than the
      activities of antioxidant enzymes, it is HSP70i that has a role to help animals
      survive during severe heat stress.

PMID- 11821494
TI  - Copper metabolism in actively growing rainbow trout (Oncorhynchus mykiss):
      interactions between dietary and waterborne copper uptake.
AB  - Juvenile rainbow trout Oncorhynchus mykiss were exposed to diets with low (12.6
      nmol g(-1)), normal (50.4 nmol g(-1)) or elevated (4437.5 nmol g(-1)) Cu
      concentrations in combination with either low (5.8 nmol l(-1)) or normal (48.5
      nmol l(-1)) waterborne Cu levels over a 50-day period, during which body mass
      increased up to fivefold. A nutritional requirement for Cu was demonstrated based
      on growth response and whole body and tissue Cu status. Simultaneous low Cu
      levels in both the water and the diet depressed growth by 31 % over 7 weeks.
      There were reductions in both specific growth rate (SGR, 1.95 versus 2.55 % day(
      1)) and food conversion efficiency (FCE, 53-59 % versus 75-80 %) over weeks 0-4,
      but these effects disappeared in weeks 4-7. Elevated concentrations of dietary Cu
      did not affect SGR or FCE. Low levels of dietary and waterborne Cu decreased, and
      high levels of dietary Cu increased, the Cu concentrations in whole body, liver,
      carcass, gut and gills. Copper levels in the liver strongly reflected the
      exposure conditions with a corresponding fivefold decrease and a 22-fold increase
      in Cu concentration. Restricting available Cu caused an exponential decline in
      whole body Cu concentration from 0.0175 to 0.0069 micromol g(-1) and increased
      the uptake of waterborne Cu (measured with (64)Cu) by the gills. Conversely, high
      levels of dietary Cu caused a linear increase in whole body Cu concentration to
      approximately 0.170 micromol g(-1) and depressed the uptake of waterborne Cu.
      Waterborne Cu uptake contributed the majority (60 %) of the body's Cu
      accumulation under Cu-deficient conditions while dietary Cu contributed the
      majority (99 %) at high dietary levels of Cu. True bioavailability of dietary Cu
      decreased with increasing levels of dietary Cu concentration, although the
      absolute amount retained increased. These findings demonstrate an important
      interaction between dietary and waterborne Cu uptake in fish and provide
      compelling evidence of a key role for the gill in Cu homeostasis.

PMID- 11821495
TI  - A controlled study of minimal-contact thermal biofeedback treatment in children
      with migraine.
AB  - OBJECTIVE: To evaluate the effectiveness of handwarming biofeedback (HWB) and
      stress management training in comparison to attention (handcooling, HCB) and wait
      list control groups. Thermal biofeedback has been used in many pediatric migraine
      treatment studies and has demonstrated a consistent therapeutic effect. No
      published studies to date have compared this treatment modality with credible
      attention control using biofeedback technology. METHODS: Thirty-six children and
      adolescents (mean age: 12.8 years), as well as the mothers and fathers of these
      children enrolled in the study, were randomly assigned to the three groups.
      Thirty-four children completed treatment. Both treatment groups received four
      sessions of biofeedback training and a portable biofeedback device for home
      practice. Ratings of treatment credibility showed that the children rated the two
      treatments as equally credible. Assessment included anxiety and depression
      questionnaires for the children and both of their parents. RESULTS: Children who
      had been assigned to the HWB group were more likely to achieve clinical
      improvement in migraine after treatment than the children in the HCB group.
      Treatment gains were maintained up to 6 months after treatment. Home practice
      data reflected a general increase in temperature in the HWB group and a decrease
      in temperature for the HCB group. CONCLUSIONS: The results of this study confirm
      the findings of earlier pediatric migraine biofeedback treatment studies and also
      provide support for the specific effect of treatments including stress management
      and HWB. Future studies with larger sample sizes will aid in delineating the
      appropriateness of HCB as a control treatment.

PMID- 11821496
TI  - Quantifying practice effects in longitudinal research with the WISC-R and WAIS-R:
      a study of children and adolescents with hemophilia and male siblings without
      hemophilia.
AB  - OBJECTIVE: To quantify practice effects associated with annual administrations of
      WISC-R and WAIS-R in children and adolescents with and without hemophilia.
      METHODS: Participants were young men (age: 7-19; 80 with hemophilia, 30 siblings)
      enrolled in the Hemophilia Growth and Development Study. Participants with
      hemophilia completed age-appropriate Wechsler scales at baseline and at four
      annual follow-ups; the siblings, at baseline and one 2-year follow-up. Regression
      analyses were used to quantify average changes in scores, adjusting for variables
      related to test performance. RESULTS: Consecutive annual evaluations were free of
      significant practice effects for 4 years with the Verbal Scale and for 2 years
      with the Performance Scale. VIQ decreased, and PIQ increased over time. Baseline
      VIQ was related to changes in VIQ; baseline PIQ and number of test-specific
      retests were related to changes in PIQ. CONCLUSIONS: The findings support use of
      Wechsler scales for annual evaluations to monitor cognitive development in
      children and adolescents.

PMID- 11821497
TI  - Family systems practice in pediatric psychology.
AB  - OBJECTIVE: To present a pediatric psychology consultation treatment framework
      based on family systems and developmental theories. METHODS: After reviewing
      background relevant to family systems interventions, a five-step protocol
      (referral, assessment, collaboration, outcome) for consultation is presented,
      using case examples from our pediatric oncology service, to illustrate joining,
      focusing, promoting competence and collaboration with patients, families, and
      staff. RESULTS: Using protocols based on family systems frameworks, pediatric
      psychologists can offer systems-oriented consultation to patients, families, and
      healthcare teams. CONCLUSIONS: Further development and evaluation of family
      systems protocols are necessary to understand the efficacy of these approaches
      and their role in training and practice.

PMID- 11821498
TI  - Interacting effects of depression and tobacco advertising receptivity on
      adolescent smoking.
AB  - OBJECTIVE: To evaluate the independent effects of exposure to others who smoke
      and receptivity to tobacco advertising on adolescent smoking practices and the
      moderating influence of depression on these relationships. METHODS: Participants
      were 1,123 high school freshmen who completed a self-report survey as part of a
      longitudinal investigation of the biobehavioral predictors of adolescent smoking
      adoption. Sixty percent of freshmen reported that they were never smokers (i.e.,
      never tried or experimented with smoking, even a few puffs), and 40% reported
      being ever smokers (i.e., ever smoked at least a partial or whole cigarette).
      RESULTS: In logistic regression models, the adjusted likelihood of ever smoking
      was greater for students reporting exposure to peer smoking. Further, a
      significant interaction was detected between receptivity to tobacco advertising
      and depression; specifically, adolescents with a high receptivity to tobacco
      advertising and clinically significant depressive symptoms were more likely to
      smoke than adolescents without these symptoms. CONCLUSIONS: Our data support the
      hypothesis that adolescents with both high advertising receptivity and depressed
      moods are most vulnerable to experiment with smoking. Tailoring prevention and
      intervention efforts to encompass tobacco advertising's effects and the role of
      depression could lead to a reduction in youth smoking.

PMID- 11821499
TI  - Daily hassles and social support as predictors of adjustment in children with
      pediatric rheumatic disease.
AB  - OBJECTIVE: To test hypotheses that social support moderates the effects of
      microstressors on the psychosocial adjustment of children with pediatric
      rheumatic diseases (PRDs) and that among multiple sources of support, classmate
      and parent support are significant predictors of adjustment, after controlling
      for demographic and disease severity variables. METHODS: Children with PRDs (N =
      160 children; 8-17 years) were recruited from three pediatric rheumatology
      centers and completed measures of daily hassles, social support, depressive
      symptoms, and state and trait anxiety; their parents completed measures of
      internalizing and externalizing behaviors. RESULTS: Fewer daily hassles and
      higher social support predicted fewer adjustment problems. Among the sources of
      support, classmate and parent support were significant predictors. Tests for
      moderation were significant only for a Hassles x Classmate Support interaction in
      the prediction of depression. A plot of the interaction between hassles and
      classmate support showed that children with high classmate support had lower
      levels of depression than children with low classmate support under high or low
      levels of daily hassles. Furthermore, children with high classmate support had
      lower levels of depression under conditions of low versus high daily hassles.
      DISCUSSION: Results are consistent with a main effect rather than buffering model
      for social support. CONCLUSIONS: Interventions should focus on management of
      daily hassles and increasing social support for children with PRDs.

PMID- 11821500
TI  - Enhancing reviews of psychological treatments with pediatric populations:
      thoughts on next steps.
AB  - OBJECTIVE: To critique the approach used by the Journal of Pediatric Psychology
      for reviews of empirical support for psychological treatments and provide
      recommendations to enhance the scientific review of interventions. METHODS:
      Application of the Chambless et al. (1996, 1998) criteria to select and describe
      empirically supported treatments was evaluated from the standpoint of method,
      theory, and clinical significance. RESULTS: While reviews of treatments based on
      the Chambless et al. (1996, 1998) criteria have provided valuable information,
      they are limited by reliance on statistical significance rather than effect sizes
      and also need to consider systematically the theoretical and clinical
      significance of intervention findings. CONCLUSIONS: Reviews of psychological
      treatments conducted with pediatric populations would be enhanced by inclusion of
      information concerning effect sizes, theory specification, and clinical
      significance. In addition, broadening the focus of initial reviews to include
      meta-analyses, clinical significance, and theory-guided interventions would
      enhance the scientific knowledge base of psychological interventions with
      pediatric populations.

PMID- 11821501
TI  - Observed and perceived dyadic and systemic functioning in families of
      preadolescents with spina bifida.
AB  - OBJECTIVE: To examine dyadic and systemic family functioning across several
      domains (conflict, cohesion, and stress) in families of preadolescents with spina
      bifida in comparison to families of able-bodied preadolescents (8- and 9-year
      olds; n = 68 in each sample). METHODS: Mother-, father-, and child-reported
      questionnaire data and observational ratings of family behavior were employed.
      RESULTS: Findings revealed significant group and socioeconomic status (SES)
      differences, particularly for the observational family data. Compared to families
      of able-bodied children, families in the spina bifida sample were less cohesive
      and children from this sample were more passive during family interaction tasks.
      Additional analyses suggested that some of these significant associations between
      group status and family functioning were mediated by verbal IQ, indicating that a
      significant portion (42%-55%) of the overall group effect was due to variations
      in child cognitive functioning. Lower SES families demonstrated higher levels of
      observed mother-child conflict, less observed and perceived family cohesion, and
      more life events. Lower SES families from the spina bifida sample appear to be
      particularly at risk for lower levels of family cohesion. CONCLUSIONS: Findings
      for the spina bifida sample support a resilience-disruption view (Costigan,
      Floyd, Harter, & McClintock, 1997) of systemic functioning in families of
      children with pediatric conditions.

PMID- 11821502
TI  - Society of pediatric psychology presidential address: toward a social ecology of
      pediatric psychology.

PMID- 11821503
TI  - Brief report: cognitive functioning in children with Tourette's syndrome with and
      without comorbid ADHD.
AB  - OBJECTIVE: To examine whether patients with Tourette's syndrome (TS) with and
      without comorbid attention deficit and hyperactivity disorder (ADHD) differ in
      cognitive functioning and whether a higher level of cognitive functioning is
      associated with severity of TS symptoms and psychosocial functioning. METHODS:
      Cognitive functioning, symptom severity, and psychosocial functioning were
      examined in 40 patients (33 boys, 7 girls; age range 6-18 years) with TS, of whom
      17 had the comorbid diagnosis of ADHD. RESULTS: Patients with a comorbid ADHD
      diagnosis evidenced poorer performance than those with TS alone with respect to
      severity of TS symptoms, psychosocial functioning, verbal and performance
      intelligence, and word fluency, but not on tests of cognitive flexibility.
      Psychosocial functioning was predicted by symptom severity, but not by
      intelligence or fluency. CONCLUSIONS: Results confirm prior findings that
      comorbid ADHD is associated with more TS symptoms and worse psychosocial and
      cognitive functioning, and motivate whether cognitive flexibility plays a role in
      moderating the deleterious psychosocial effects of Tourette's syndrome and ADHD.

PMID- 11821504
TI  - Brief report: behaviors identified by caregivers to detect pain in
      noncommunicating children.
AB  - OBJECTIVE: To develop an observational measure, based on caregiver reports, to
      assess chronic pain in children with significant cognitive impairment who are
      unable to communicate verbally. The issue of whether these children share a core
      set of cues to express pain was investigated. METHODS: Specific pain cues were
      elicited during detailed interviews with 29 female caregivers of noncommunicating
      children. Pain cues were categorized by a two-stage Delphi process and cues
      indicating severe and definite pain identified. RESULTS: Six cues from five
      different categories were used by 90% of caregivers to identify definite or
      severe pain in their child. CONCLUSIONS: Although the specific expression of pain
      may be very individual, there is a shared set of core pain cues. The relationship
      between these cues and evidence of pain and distress is discussed.

PMID- 11821505
TI  - A needle in a haystack of genes.

PMID- 11821506
TI  - Daily hemodialysis and the outcome of acute renal failure.
AB  - BACKGROUND: Intermittent hemodialysis is widely used as renal-replacement therapy
      in patients with acute renal failure, but an adequate dose has not been defined.
      We performed a prospective study to determine the effect of daily intermittent
      hemodialysis, as compared with conventional (alternate-day) intermittent
      hemodialysis, on survival among patients with acute renal failure. METHODS: A
      total of 160 patients with acute renal failure were assigned to receive daily or
      conventional intermittent hemodialysis. Survival was the primary end point of the
      study. The duration of acute renal failure and the frequency of therapy-related
      complications were secondary end points. RESULTS: The two study groups were
      similar with respect to age, sex, cause and severity of acute renal failure,
      medical or surgical intensive care setting, and the score on the Acute
      Physiology, Age, and Chronic Health Evaluation. Daily hemodialysis resulted in
      better control of uremia, fewer hypotensive episodes during hemodialysis, and
      more rapid resolution of acute renal failure (mean [+/-SD], 9+/-2 vs. 16+/-6
      days; P=0.001) than did conventional hemodialysis. The mortality rate, according
      to the intention-to-treat analysis, was 28 percent for daily dialysis and 46
      percent for alternate-day dialysis (P=0.01). In a multiple regression analysis,
      less frequent hemodialysis (on alternate days, as opposed to daily) was an
      independent risk factor for death. CONCLUSIONS: The high mortality rate among
      critically ill patients with acute renal failure who require renal-replacement
      therapy is related to both coexisting conditions and uremic damage to other organ
      systems. Intensive hemodialysis reduces mortality without increasing
      hemodynamically induced morbidity.

PMID- 11821507
TI  - Detection of APC mutations in fecal DNA from patients with colorectal tumors.
AB  - BACKGROUND: Noninvasive methods for detecting colorectal tumors have the
      potential to reduce morbidity and mortality from this disease. The mutations in
      the adenomatous polyposis coli (APC) gene that initiate colorectal tumors
      theoretically provide an optimal marker for detecting colorectal tumors. The
      purpose of our study was to determine the feasibility of detecting APC mutations
      in fecal DNA with the use of newly developed methods. METHODS: We purified DNA
      from routinely collected stool samples and screened for APC mutations with the
      use of a novel approach called digital protein truncation. Many different
      mutations could potentially be identified in a sensitive and specific manner with
      this technique. RESULTS: Stool samples from 28 patients with nonmetastatic
      colorectal cancers, 18 patients with adenomas that were at least 1 cm in
      diameter, and 28 control patients without neoplastic disease were studied. APC
      mutations were identified in 26 of the 46 patients with neoplasia (57 percent; 95
      percent confidence interval, 41 to 71 percent) and in none of the 28 control
      patients (0 percent; 95 percent confidence interval, 0 to 12 percent; P<0.001).
      In the patients with positive tests, mutant APC genes made up 0.4 to 14.1 percent
      of all APC genes in the stool. CONCLUSIONS: APC mutations can be detected in
      fecal DNA from patients with relatively early colorectal tumors. This feasibility
      study suggests a new approach for the early detection of colorectal neoplasms.

PMID- 11821509
TI  - Gastropericardial fistula after laparoscopic surgery for reflux disease.

PMID- 11821508
TI  - A comparison of oral and topical corticosteroids in patients with bullous
      pemphigoid.
AB  - BACKGROUND: Bullous pemphigoid is the most common autoimmune blistering skin
      disease of the elderly. Because elderly people have low tolerance for standard
      regimens of oral corticosteroids, we studied whether highly potent topical
      corticosteroids could decrease mortality while controlling disease. METHODS: A
      total of 341 patients with bullous pemphigoid were enrolled in a randomized,
      multicenter trial and stratified according to the severity of their disease
      (moderate or extensive). Patients were randomly assigned to receive either
      topical clobetasol propionate cream (40 g per day) or oral prednisone (0.5 mg per
      kilogram of body weight per day for those with moderate disease and 1 mg per
      kilogram per day for those with extensive disease). The primary end point was
      overall survival. RESULTS: Among the 188 patients with extensive bullous
      pemphigoid, topical corticosteroids were superior to oral prednisone (P=0.02).
      The one-year survival rate was 76 percent in the topical-corticosteroid group and
      58 percent in the oral-prednisone group. Disease was controlled at three weeks in
      92 of the 93 patients in the topical-corticosteroid group (99 percent) and 86 of
      the 95 patients in the oral-prednisone group (91 percent, P=0.02). Severe
      complications occurred in 27 of the 93 patients in the topical-corticosteroid
      group (29 percent) and in 51 of the 95 patients in the oral-prednisone group (54
      percent, P=0.006). Among the 153 patients with moderate bullous pemphigoid, there
      were no significant differences between the topical-corticosteroid group and the
      oral-prednisone group in terms of overall survival, the rate of control at three
      weeks, or the incidence of severe complications. CONCLUSIONS: Topical
      corticosteroid therapy is effective for both moderate and severe bullous
      pemphigoid and is superior to oral corticosteroid therapy for extensive disease.

PMID- 11821510
TI  - Images in clinical medicine. Clostridium difficile colitis.

PMID- 11821511
TI  - Clinical practice. Antibiotic-associated diarrhea.

PMID- 11821512
TI  - Production and actions of estrogens.

PMID- 11821514
TI  - Daily hemodialysis--will treatment each day improve the outcome in patients with
      acute renal failure?

PMID- 11821513
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 4-2002. A 75-year-old man with acute renal failure five months
      after cystoprostatectomy and urethrectomy for carcinoma.

PMID- 11821515
TI  - Advances in our electronic pages.

PMID- 11821516
TI  - Bullous pemphigoid therapy -- think globally, act locally.

PMID- 11821517
TI  - Removing career obstacles for young physician-scientists -- loan-repayment
      programs.

PMID- 11821518
TI  - Allocating limited resources.

PMID- 11821519
TI  - Educational-debt relief for clinical investigators--a vote of confidence.

PMID- 11821520
TI  - Copper intrauterine devices and tubal infertility among nulligravid women.

PMID- 11821521
TI  - GB virus C and mortality from HIV infection.

PMID- 11821522
TI  - Cardiac rehabilitation.

PMID- 11821523
TI  - Cephalosporin allergy.

PMID- 11821524
TI  - Case 29-2001: oncogenic hypophosphatemic osteomalacia.

PMID- 11821525
TI  - The ethics of placebo-controlled trials.

PMID- 11821526
TI  - Cesium-induced torsades de pointes.

PMID- 11821527
TI  - pH Homeostasis of cellular organelles.
AB  - An optimal pH is maintained in each secretory and endocytic organelle by the
      balance between active H(+) pumping and passive H(+) efflux. The progressive
      acidification of secretory organelles does not reflect an increased proton
      pumping activity but rather the decreased conduction of a "proton leak" pathway
      resembling the recently cloned voltage-gated proton channels.

PMID- 11821529
TI  - Thrombopoietin: the novel hepatic hormone.
AB  - The glycoprotein thrombopoietin (TPO) is the major stimulator of megakaryopoiesis
      and platelet production. Hepatocytes express TPO mRNA at a constant rate. The
      plasma TPO level is inversely correlated to the mass of megakaryocytes and
      platelets, which degrade the hormone following its binding to specific membrane
      receptors.

PMID- 11821530
TI  - Of mice and worms: novel insights into ClC-2 anion channel physiology.
AB  - ClC anion channels are found in all major groups of organisms. Recent studies in
      nematodes and mice suggest that the function and regulation of ClC-2 have been
      conserved over vast evolutionary time spans. These studies illustrate the
      experimental advantages of using genomically defined nonmammalian model organisms
      for characterizing ClC channel functional genomics.

PMID- 11821531
TI  - Muscle fatigue: lactic acid or inorganic phosphate the major cause?
AB  - Intracellular acidosis due mainly to lactic acid accumulation has been regarded
      as the most important cause of skeletal muscle fatigue. Recent studies on
      mammalian muscle, however, show little direct effect of acidosis on muscle
      function at physiological temperatures. Instead, inorganic phosphate, which
      increases during fatigue due to breakdown of creatine phosphate, appears to be a
      major cause of muscle fatigue.

PMID- 11821532
TI  - Human myoblast differentiation: Ca(2+) channels are activated by K(+) channels.
AB  - In a paradigm of cellular differentiation, human myoblast fusion, we investigated
      how a Ca(2+) influx, indispensable for fusion, is triggered. We show how newly
      expressed Kir2.1 K(+) channels, via their hyperpolarizing effect on the membrane
      potential, generate a window Ca(2+) current (mediated by alpha 1H T-type Ca(2+)
      channels), which causes intracellular Ca(2+) to rise.

PMID- 11821533
TI  - Astrocytes function in matching blood flow to metabolic activity.
AB  - The brain possesses an intrinsic regulatory mechanism to maintain an adequate
      supply of O(2) and nutrition despite local increases in neuronal activity. Brain
      astrocytes function as an intermediary cell type by responding to glutamate
      released from activated neurons, and they couple cerebral blood flow by producing
      cytochrome P-450-derived epoxyeicosatrienoic acids that induce vasodilation and
      increase capillary density.

PMID- 11821534
TI  - From funny current to HCN channels: 20 years of excitation.
AB  - The "funny" (pacemaker) current has unusual characteristics, including activation
      on hyperpolarization, permeability to K(+) and Na(+), modulation by internal
      cAMP, and a tiny, single-channel conductance. In cardiac cells and neurons,
      pacemaker channels control repetitive activity and excitability. The recent
      cloning of HCN subunits provides new insight into the molecular basis for the
      funny channel properties.

PMID- 11821535
TI  - Is there a mind? Electrophysiology of unconscious patients.
AB  - Event related brain potentials (ERPs) provide information about cortical
      processing in severe neurological patients whose cognitive abilities cannot be
      expressed in their behavior. In coma, ERPs contribute to the prediction of the
      outcome. In a vegetative state, ERPs uncover the functional state of cortical
      processes. The significance of ERPs in the neurophysiological study of
      consciousness is discussed.

PMID- 11821536
TI  - The physiologist's ethical dilemmas.

PMID- 11821537
TI  - Physically restraining children at home or school.

PMID- 11821539
TI  - Patient page. Consumer & family information: distress, stress, or mental
      disorder?

PMID- 11821540
TI  - Datapoints: use of restraint before and after implementation of the new HCFA
      rules.

PMID- 11821541
TI  - Psychopharmacology: principles for starting, stopping, or switching medications.

PMID- 11821542
TI  - Practical Psychotherapy: working with a patient's defenses in supportive
      psychotherapy.

PMID- 11821543
TI  - Economic grand rounds: the business case for high-quality mental health care.

PMID- 11821544
TI  - Personal accounts: an account of multiple psychiatric hospitalizations in the
      1960s.

PMID- 11821545
TI  - Best Practices: New York state's campaign to implement evidence-based practices
      for people with serious mental disorders.

PMID- 11821547
TI  - Implementing dialectical behavior therapy.
AB  - Dialectical behavior therapy (DBT) is a cognitive-behavioral approach to treating
      borderline personality disorder. Early empirical results are promising, although
      they are not sufficient to establish DBT as an evidence-based practice in
      community settings. Nevertheless, the treatment has been widely implemented by
      mental health authorities, program leaders, and clinicians. The authors describe
      DBT's four stages of treatment, the functional areas addressed, and the treatment
      modes used as well as the reasons for the appeal of DBT to practitioners. They
      review barriers encountered by those who have implemented the model and present
      strategies that have been developed to overcome the barriers.

PMID- 11821546
TI  - Managed behavioral health care in the public sector: will it become the third
      shame of the States?
AB  - Managed behavioral health care is increasingly being used in public mental health
      systems. While supporters cite potential benefits, critics describe dire
      consequences for individuals with serious, long-term mental illness. The
      situation has parallels with the major changes resulting from
      deinstitutionalization some four decades ago. Believing that analyzing history
      may prevent repeating some of its mistakes, the authors compare the antecedents,
      benefits, and negative effects of deinstitutionalization with those of the public
      sector managed behavioral health care systems being developed today. Lessons
      learned from the earlier era include the need for careful general and technical
      planning; for assignment of responsibility, including monitoring, to the public
      sector; and for a focus on clients and the special needs generated by severe
      mental illnesses.

PMID- 11821549
TI  - A university-state-corporation partnership for providing correctional mental
      health services.
AB  - In September 1998 the University of Massachusetts Medical School, in partnership
      with a private vendor of correctional health care, began providing mental health
      services and other services to the Massachusetts Department of Correction. The
      experience with this partnership demonstrates that the involvement of a medical
      school with a correctional system has advantages for both. The correctional
      program benefits from enhanced quality of services, assistance with the
      recruitment and retention of skilled professionals, and expansion of training and
      continuing education programs. The medical school benefits by building its
      revenue base while providing a needed public service and through opportunities to
      extend its research and training activities. Successful collaboration requires
      that the medical school have an appreciation of security needs, a sensitivity to
      fiscal issues, and a readiness to work with inmates who have severe mental
      disorders and disruptive behavior. Correctional administrators, for their part,
      must support adequate treatment resources and must collaborate in the resolution
      of tensions between security and health care needs.

PMID- 11821548
TI  - Appropriateness of prescribing practices for serotonergic antidepressants.
AB  - OBJECTIVE: Data from prescribing physicians were used to assess whether
      serotonergic antidepressants were used for appropriate indications and at
      appropriate initial dosages. METHODS: Data were derived from the confidential
      logs of psychiatrists and primary care physicians who provided prescription
      information from January 1, 1997, through June 30, 1999, as part of the National
      Disease and Therapeutic Index physician survey. The survey is not affiliated with
      a reimbursement system and therefore minimizes bias related to reimbursement.
      Data on the primary reason for use and the dosage at the time of first use were
      obtained for prescriptions of citalopram, fluoxetine, paroxetine, sertraline,
      venlafaxine, and extended-release venlafaxine. RESULTS: Depressive disorders
      accounted for the majority of the 3,206 prescriptions for the six antidepressants
      (74 percent to 86.2 percent). The next most common indications for use were
      anxiety (4.1 percent to 12.6 percent) and obsessive-compulsive disorder (1.3
      percent to 3.3 percent). For patients with depressive disorders, psychiatrists
      prescribed slightly higher antidepressant dosages than primary care physicians.
      CONCLUSIONS: Serotonergic antidepressants are used primarily for the treatment of
      depression and depression-related disorders and are prescribed at the recommended
      starting dosages.

PMID- 11821550
TI  - Representative payee programs for persons with mental illness in Illinois.
AB  - OBJECTIVE: Representative payee programs can improve the community tenure of
      persons with mental illness by ensuring that their basic needs, such as housing,
      are met. The authors conducted a survey to assess the extent to which
      representative payee programs are provided by community mental health centers and
      the criteria used in enrolling clients in these services. METHODS: Community
      mental health centers under contract to the Illinois Department of Human Services
      participated in a census survey. Survey questions concerned provision of
      representative payee programs, service characteristics, and criteria for
      enrollment in the programs. RESULTS: Representative payee programs were directly
      provided by 59 percent of the 95 community mental health centers in the sample.
      More than a third of clients who were receiving intensive services had a
      representative payee. More than three times as many such clients had a
      representative payee when agencies provided representative payee programs
      directly rather than through referrals of family members. Frequently cited
      criteria for enrollment in a representative payee program included a lack of
      financial skills (89 percent), a lack of rent money (52 percent), substance abuse
      (50 percent), homelessness (33 percent), and frequent (37 percent) or long-term
      (30 percent) hospitalization. The majority of the representative payee programs
      (76 percent) provided this service to clients who received representative payee
      services under the mandate of the Social Security Administration. CONCLUSIONS:
      Given the high proportion of clients of agencies that directly provided
      representative payee services who were assigned to a representative payee, all
      community mental health centers that provide intensive services should also
      directly provide representative payee services in order to improve access to
      representative payee services.

PMID- 11821551
TI  - Use and costs of public-sector behavioral health services for african-american
      and white women.
AB  - OBJECTIVE: The purpose of this study was to identify differences between African
      American and white women in the use of behavioral health services and factors
      associated with these differences. METHODS: In one large public behavioral health
      system, data on demographic characteristics, financial resources, clinical
      disorders, service use patterns, and costs of care were analyzed for 10,905
      African-American and 19,069 white women between the ages of 18 and 59 years who
      received behavioral health services in 1997. RESULTS: The African-American women
      were more likely to be older, never married, unemployed, and eligible for
      Medicaid and to have a diagnosis of a psychotic disorder or a substance use
      disorder. African-American women were more likely than white women to receive
      inpatient substance abuse services and to receive more community-based day
      treatment services, medication services, and case management services. However,
      the costs of that care differed by only 2 to 4 percent from those for white
      women. Presence of a psychotic disorder and co-occurring substance use-need
      related factors-were significant predictors of higher inpatient care costs for
      all the women in the sample. Presence of a psychotic or major affective disorder
      and eligibility for Medicaid-an enabling factor-were the most significant
      predictors of higher outpatient costs for the sample. Receipt of more community
      based services was significantly and inversely related to inpatient care costs,
      regardless of race. CONCLUSIONS: In this sample of African-American and white
      women, consumers' needs were a significant predictor of service use. Patterns of
      care that were tailored to consumers' needs were not significantly more costly
      overall.

PMID- 11821552
TI  - Symptoms and deviant behavior among eight-year-olds as predictors of referral for
      psychiatric evaluation by age 12.
AB  - OBJECTIVE: This study examined whether psychiatric symptoms and deviant behavior
      among eight-year-old children predicted referral for a psychiatric consultation
      by age 12. METHODS: A total of 1,268 children in Finland were assessed at age
      eight and again four years later. Three questionnaires-the Rutter A2 Scale for
      parents, the Rutter B2 Scale for teachers, and the Children's Depression
      Inventory (CDI)-were used at both time points. Other variables were socioeconomic
      status, family structure, and residence in an urban, rural, or semirural
      environment. One-way analysis of variance was used, and risk ratios were
      calculated to assess the extent to which children who were later referred for
      evaluation or for whom referral was considered were likely to have had scale
      scores in the deviant range at age eight. RESULTS: Only 3.3 percent of the
      children had been referred for an evaluation by age 12. Referral had been
      considered for another 2.9 percent of the children. The deviance scores of the
      referred children and those considered for referral were significantly higher on
      all scales at both time points. When the analysis controlled for gender and the
      other variables, the referred children were more likely than those not referred
      or considered for referral to have had high scores four years earlier on the
      teachers' scale and on the CDI. Children considered for referral were more likely
      than those not referred or considered for referral to be male and to have scored
      high on the CDI four years earlier. CONCLUSIONS: Psychiatric problems of younger
      children predict referral for psychiatric evaluation years later.

PMID- 11821553
TI  - A comparison of experts' perspectives on assertive community treatment and
      intensive case management.
AB  - This study compared experts' views on the critical ingredients of assertive
      community treatment and intensive case management. Twenty experts on assertive
      community treatment and 22 experts on intensive case management rated the
      importance of 40 elements common to each treatment approach. The assertive
      community treatment experts gave higher importance ratings than the intensive
      case management experts to 37 of the 40 items; for 21 of these items, the ratings
      were significantly higher. Differences in importance ratings were greatest for
      organizational and structural elements and smallest for treatment goals. The
      results of this study indicate that although intensive case management resembles
      assertive community treatment in most respects, assertive community treatment may
      be a more clearly articulated model overall.

PMID- 11821554
TI  - The influence of patients' compensation-seeking status on the perceptions of
      veterans affairs clinicians.
AB  - The study compared clinicians' perceptions of three groups of veterans with
      posttraumatic stress disorder (PTSD): those seeking compensation for PTSD, those
      not seeking compensation, and those certified as permanently disabled and thus
      not needing to reapply for benefits. The study subjects were 50 clinicians
      working in specialized PTSD programs of the Department of Veterans Affairs. The
      clinicians had a more negative view of the treatment engagement of veterans who
      were seeking compensation and of clinical work with these patients than they did
      in the case of the other two groups. The longer clinicians had been working with
      veterans who had PTSD, the more extreme were these negative perceptions. Most
      clinicians expressed a belief that the pursuit of service connection for PTSD has
      a negative impact on the therapeutic relationship and on clinical work in
      general.

PMID- 11821555
TI  - When taking medications is a sin.

PMID- 11821557
TI  - Prescriptions of medications to youths.

PMID- 11821558
TI  - Rational and irrational polypharmacy.

PMID- 11821560
TI  - Mental health problems in transition: challenges for psychiatry in Hong Kong.

PMID- 11821559
TI  - Dissemination of skills training.

PMID- 11821561
TI  - The effects of different dosages of oestrogen on the bone mineral density of
      postmenopausal Hong Kong Chinese women: randomised controlled trial.
AB  - OBJECTIVE: To determine the effects of different dosages of conjugated equine
      oestrogen on the bone mineral density of postmenopausal Hong Kong Chinese women.
      DESIGN: A 1-year three-arm randomised controlled trial. SETTING: Out-patient
      setting at a governmental hospital in Hong Kong. PARTICIPANTS: One hundred and
      five women aged 45 years or older, in whom menopause had occurred not more than 2
      years previously. INTERVENTION: Women were assigned randomly to treatment with
      conjugated equine oestrogen 0.625 mg/d or 0.3 mg/d, or no oestrogen. MAIN OUTCOME
      MEASURE: Bone mineral density. RESULTS: Women who were assigned to the control
      group showed a significant reduction in bone mineral density in both the femoral
      neck and the lumbar spine (3.6%; P=0.001 and 4.0%; P<0.001, respectively). Those
      who received oestrogen 0.3 mg/d showed a significant reduction (3.9%; P=0.010)
      and a non-significant reduction (2.2%; P=0.141) in their lumbar spine and femoral
      neck bone mineral densities, respectively. In contrast, there was little change
      in the spinal and femoral neck bone mineral densities in women who received
      estrogen 0.625 mg/d. CONCLUSION: The minimum effective dosage of conjugated
      equine oestrogen to prevent osteoporosis in postmenopausal Hong Kong Chinese
      women is 0.625 mg/d. The bone mineral density, however, was maintained but not
      increased.

PMID- 11821562
TI  - A comparison of pregnancy outcome between high-order multiple and twin
      pregnancies: matched-pair retrospective study.
AB  - OBJECTIVE: To compare the pregnancy outcome between high-order multiple and twin
      pregnancies. DESIGN: Matched-pair retrospective analysis. SETTING: University
      teaching hospital, Hong Kong. PATIENTS: Patient records from 38 high-order
      multiple pregnancies that were delivered over a period of 15 years, and those
      from matched twin pregnancies. MAIN OUTCOME MEASURES: Obstetric and perinatal
      outcomes. RESULTS: The incidence of high-order multiple pregnancies increased
      over the study period in association with the more frequent practice of ovulation
      induction and other assisted reproductive techniques. High-order multiple
      pregnancies were associated with a higher incidence of maternal complications and
      a significantly higher perinatal mortality rate than were twin pregnancies.
      CONCLUSION: Efforts should be made to prevent multiple pregnancies by carefully
      monitoring ovulation treatment and by limiting the number of embryos transferred.

PMID- 11821563
TI  - Parental anxiety associated with participation in anaesthetic induction in
      children: questionnaire survey.
AB  - OBJECTIVES: To determine the reasons why Chinese parents accompany their child
      during anaesthetic induction; to explore the level of anxiety experienced by the
      parents; and to evaluate the factors that contribute to parental anxiety. DESIGN:
      Questionnaire study of Chinese parents who had chosen to be present during the
      anaesthetic induction of their child between January 1997 and July 1997. SETTING:
      Day Surgery Unit at a public hospital, Hong Kong. PARTICIPANTS: One hundred and
      fifty-one Chinese parents of 151 children undergoing general anaesthesia for
      surgery. MAIN OUTCOME MEASURE: Parental anxiety, as evaluated by a self-reported
      rating system and the State-Trait Anxiety Scale. RESULT: More than half (56%) of
      the participants graded their experience as either "very anxious but tolerable"
      or "a little anxious", and only 2% graded the situation as "very anxious,
      intolerable". All participants were either "satisfied" or "very satisfied" with
      their experience. The type of surgery and any history of previous surgical
      intervention were found to be factors that determined the level of anxiety
      (P<0.05). CONCLUSIONS: Most Chinese parents decide to be present at their child's
      anaesthetic induction because of a sense of duty and concern. Parental presence
      does not provoke further or intolerable parental anxiety. One limitation of this
      study is that the level of anxiety measured might be due to the combination of
      anaesthetic induction and surgery rather than to concerns about anaesthetic
      induction alone.

PMID- 11821564
TI  - Anaesthesia for liver transplantation: experience at a teaching hospital.
AB  - OBJECTIVE: To assess the anaesthetic aspects of liver transplantation. DESIGN:
      Retrospective study. SETTING: University teaching hospital, Hong Kong. PATIENTS:
      The first 55 patients who received liver transplantations between 5 October 1991
      and 14 June 1997. MAIN OUTCOME MEASURES: The anaesthetic technique used;
      indications for liver transplantation and type of graft transplanted; survival
      rate; duration of anaesthesia and surgical starting time; intra-operative changes
      associated with major transfusion; frequency of hypothermia, coagulopathy, and
      reperfusion; frequency of use of cell saver devices, veno-venous bypass, and a
      rapid infusion system; and associated complications. RESULTS: All patients
      received general anaesthesia with rapid sequence induction. Most adult recipients
      had cirrhosis from various causes, whereas biliary atresia was the most common
      condition in the paediatric population. Both cadaveric and living-related liver
      transplantations were performed, and the overall 1-year survival rate of patients
      who received a transplantation before June 1996 was 85%. Veno-venous bypass was
      used in 84% of adults, but in none of the paediatric patients; a cell saver
      device was used for all adult patients and 92% of paediatric patients. All
      transplant recipients had acidosis, hypothermia, and hypotension during the
      operation. CONCLUSIONS: Liver transplantation is no longer experimental. It is
      the therapeutic option for patients with chronic liver failure. Good anaesthetic
      support is an essential element of a liver transplantation service.

PMID- 11821565
TI  - Geriatric screening in acute care wards--a novel method of providing care to
      elderly patients.
AB  - OBJECTIVE: To assess a nurse-implemented geriatric screening system. DESIGN:
      Descriptive study. SETTING: University teaching hospital, Hong Kong. PATIENTS:
      All (5080) elderly patients admitted between 1 January 1996 and 31 December 1996.
      MAIN OUTCOME MEASURES: Patient characteristics such as disease, prior admission,
      living quarters, and regular medications; interventions taken; and morbidity and
      mortality. RESULTS: The most common interventions were referral to a convalescent
      hospital, patient education, and carer contact. The overall death rate was 8.5%
      and the diseases with the highest mortality rates were renal failure, liver
      cirrhosis, and cancer. Approximately one quarter of patients had been admitted to
      hospital in the previous month. The death rate was higher among women than men
      (10.8% versus 6.7%, P<0.001; odds ratio=1.68; 95% confidence interval, 1.38
      2.05), as was the percentage of those with a history of admission in the previous
      month (32.8% versus 20.0%, P<0.001; odds ratio=1.95; 95% confidence interval,
      1.71-2.21). Patients with multiple pathologies and polypharmacy had a greater
      frequency of previous 1-month admission compared with those who did not have
      these features (37.5% versus 20.0%, P<0.001; odds ratio=2.37; 95% confidence
      interval 2.0-2.7). Patients living in old-age homes had a higher death rate and
      more previous 1-month admissions than home dwellers, and patients living in
      private old-age homes had a higher death rate but lower number of previous 1
      month admissions than those living in subsidised old-age homes. CONCLUSIONS: This
      study has collected important data from one form of integrated geriatric
      practice, which can be used for future service provision.

PMID- 11821566
TI  - What should be done about postnatal depression in Hong Kong?
AB  - Postnatal depression is one of the most common forms of psychiatric morbidity of
      child-bearing and causes a host of adverse psychosocial complications to the
      mother, the children, and the family. Recent studies have shown that 12% of local
      women have postnatal depression and most of them receive no meaningful medical
      attention. The validation of a local version of the Edinburgh Postnatal
      Depression Scale has made systematic screening for postnatal depression feasible.
      However, such a screening programme should be backed up by well-resourced
      counselling and psychiatric services. Much remains to be done if a reasonable
      level of post-partum psychological care is to be provided. Additional funding is
      required to train nurse counsellors and set up postnatal mental health teams, as
      well as mother and child units.

PMID- 11821567
TI  - The provision of care for women with postnatal mental disorder in the United
      Kingdom: an overview.
AB  - Childbirth is a life event and is linked universally with cultural significance.
      It is sometimes associated with mental disorders, which need special assessment
      and treatment. This review describes the service provision for women with
      puerperal mental disorder in the United Kingdom.

PMID- 11821568
TI  - The role of social workers in the Hong Kong psychiatric service.
AB  - The role of social workers within the Hong Kong psychiatric service is not
      satisfactory. This paper argues that these roles should be flexibly re-examined
      and revised, so that the needs of mentally ill patients and their families and
      new challenges faced by the mental health service can be met. To enhance service
      quality, social workers employed in a psychiatric setting need to improve their
      manpower ratio, gain professional knowledge, be involved in clinical supervision,
      coordinate teamwork, assume an active role in policy change and advocacy, and
      engage in empirically based research.

PMID- 11821569
TI  - Early intervention in schizophrenia patients--rationale for its implementation
      and practice.
AB  - This review examines the clinical and theoretical evidence justifying early
      intervention in individuals with schizophrenia. Potential reasons for the
      previous lack of emphasis on early intervention are discussed. Interventions that
      target psychosis are distinguished from those that work on prodromal symptoms. It
      is suggested that early intervention programmes should try to reduce the duration
      of untreated psychosis. The relationship between this and outcome is discussed.
      Improving service accessibility alone may not be sufficient, and education and
      destigmatisation input may be required. Once a patient is identified, vigorous
      pharmacological and psychosocial interventions are important to improve the long
      term clinical outcome. An effective early intervention programme for psychosis
      provides a basis for the future development of a prodrome intervention programme.

PMID- 11821570
TI  - Severe necrotising fasciitis of the extremities caused by Vibrionaceae:
      experience of a Hong Kong tertiary hospital.
AB  - Necrotising fasciitis is an uncommon soft tissue infection characterised by the
      widespread necrosis of subcutaneous tissue and fascia, and secondary necrosis of
      the overlying skin. Ten patients who had necrotising fasciitis were admitted to
      the intensive care unit at the Prince of Wales Hospital between June 1994 and
      August 1997. The necrosis in six patients was caused by marine Vibrionaceae.
      Because of the rapid onset of necrosis, progression to severe disease, and
      frequently fatal outcome, the public (especially at-risk individuals), general
      practitioners, and specialist medical personnel should be made aware of the
      clinical syndrome of necrotising fasciitis caused by marine Vibrionaceae. The
      diagnosis is dependent on a high index of suspicion, which should be aroused by
      the presentation of an immunocompromised patient with an extremity lesion and a
      history of contact with raw seafood or a warm aquatic environment. Once the
      disease is suspected, treatment should be a course of a third-generation
      cephalosporin, and fluoroquinolone or tetracycline. Aggressive surgical
      debridement is recommended.

PMID- 11821571
TI  - Successful pregnancy in a case of azoospermic infertility by using testicular
      sperm for intracytoplasmic injection into the oocyte.
AB  - Non-obstructive azoospermia used to be considered an untreatable cause of
      infertility. By the microinjection technique, however, sperm that has been
      surgically extracted from the testis can be injected into the oocyte cytoplasm.
      The injected eggs can be transferred to the uterus or fallopian tubes to initiate
      a pregnancy. A healthy baby boy conceived by using this method was delivered in
      November 1997. This micromanipulation technique offers couples in which the man
      has non-obstructive azoospermia the chance of having their own offspring. The
      methodology used and a brief discussion of its merits are presented.

PMID- 11821572
TI  - Spontaneous regression of renal cell carcinoma metastases.
AB  - Spontaneous regression of some tumours is known to occur. We report here on a
      patient who developed lung and scalp metastases from renal cell carcinoma
      approximately 1 year after undergoing a radical nephrectomy. The lung metastasis
      was documented by computed tomography and histological examination. A spontaneous
      complete regression of the lung and scalp metastases occurred. Shortly after,
      however, a brain metastasis developed in the absence of any radiographic evidence
      of recurrence in the primary site or the lung.

PMID- 11821573
TI  - Falloposcopy--a prerequisite to the proper assessment of tubal infertility.
AB  - OBJECTIVE: To review the technique and results of falloposcopy, and the
      classification and management of fallopian tube disease. DATA SOURCES: Medline
      and non-Medline search of the relevant English literature, and personal
      experience. STUDY SELECTION: Studies involving the use of falloposcopy to assess
      tubal status were selected for review. DATA EXTRACTION: The procedure of
      falloposcopy and its possible problems and complications were studied. Results
      from falloposcopy were compared with those from conventional investigations of
      tubal status, and their correlation with pregnancy was evaluated. DATA SYNTHESIS:
      Falloposcopy gives a better assessment of tubal status than conventional methods
      and can also predict the subsequent pregnancy rate. By falloposcopy, the decision
      of the mode of therapy for subfertility can be changed in more than 60% of
      patients. CONCLUSION: Examination of the fallopian tube using falloposcopy allows
      an accurate assessment of the tubal status to be made and is a prerequisite to
      deciding the most appropriate mode of assisted reproductive therapy.

PMID- 11821574
TI  - Surgical wound infection.
AB  - OBJECTIVE: To review the risk factors for surgical wound infection; the use of
      prophylactic antibiotics in the prevention of wound infection; and the benefits
      of wound surveillance programmes to reduce the rate of surgical wound infection.
      DATA SOURCES: Medline literature search and review of published work on surgical
      wound infection, and the references cited in them. STUDY SELECTION: Critical
      studies containing supporting evidence were selected. DATA EXTRACTION: Data were
      extracted independently by multiple observers. DATA SYNTHESIS: Factors that
      affect the susceptibility of a wound to infection include a pre-existing illness,
      the duration of the operative procedure, wound contamination, three or more
      diagnoses at the time of discharge, and abdominal operations. Antibiotic
      prophylaxis can decrease postoperative morbidity, shorten hospital stay, and
      reduce overall costs attributable to infection; the choice of antibiotic depends
      on the wound class. Wound surveillance can also decrease wound infection rates.
      CONCLUSION: Surgical wound infections are common and consume a considerable
      portion of health care finances. A reduction in the infection rate to a minimal
      level, however, can be achieved by the judicious use of antibiotic prophylaxis
      and the use of an organised system of wound surveillance and reporting.

PMID- 11821575
TI  - Influenza surveillance in Hong Kong: results of a trial Physician Sentinel
      Programme.
AB  - The H5N1 influenza outbreak in Hong Kong at the end of 1997 emphasised the need
      for viral surveillance so that new influenza epidemics can be foreseen. Although
      South China is regarded as the regional epicentre of influenza epidemics, there
      has been little epidemiological documentation of the disease there. A sentinel
      physician network was established in Hong Kong in 1993 to estimate the incidence,
      severity, and seasonality of influenza-like illnesses and to provide data on the
      demand for health care that is related to this illness. Influenza-like illness
      occurred throughout the year of the survey, peaking from March through May and
      accounting for 15% of doctor visits. The incidence was approximately 117 in 1000
      patients and was greatest among children aged 1 to 4 years. Ongoing physician
      surveillance with appropriate coverage of the general population supported by a
      laboratory virus isolation capability may help control future influenza
      outbreaks.

PMID- 11821576
TI  - Condyloma acuminatum of the uterine cervix.

PMID- 11821577
TI  - Anonymous retrospective HIV tesing in Chinese patients with non-Hodgkin's
      lymphoma.

PMID- 11821578
TI  - Helicobacter pylori--what do we know?

PMID- 11821579
TI  - Cardiopulmonary response to exercise of 8- and 13-year-old Chinese children in
      Hong Kong: results of a pilot study.
AB  - OBJECTIVES: To assess the cardiopulmonary response of healthy Hong Kong Chinese
      children to the treadmill test, and to identify anthropometric factors that may
      be related to fitness. DESIGN: Cross-sectional study. SETTING: University
      teaching hospital, Hong Kong. PARTICIPANTS: Forty-three 8-year-old and fifty
      seven 13-year-old healthy Chinese children from middle or lower socio-economic
      class families in Shatin and nearby areas. MAIN OUTCOME MEASURES: The forced
      vital capacity, 1-second forced expiratory volume, pulse rate, and blood pressure
      were measured before and after undertaking the treadmill test (Bruce protocol).
      The endurance time until volitional exhaustion, the number of metabolic
      equivalents of energy used, and the sum of the skinfold thicknesses were also
      obtained. RESULTS: Multiple regression analysis showed that the sum of the
      skinfold thicknesses was positively associated with pulse rate and diastolic
      blood pressure at all stages of exercise, and was negatively associated with the
      endurance time of and number of metabolic equivalents of energy used by the 8
      year-old children. The 13-year-old children had a longer cardiopulmonary
      endurance than the 8-year-old children. In both age-groups, pulmonary function
      was positively associated with height and weight. CONCLUSION: The study provides
      useful reference data for Hong Kong Chinese 8- and 13-year-old children when
      subjected to the treadmill test. A larger study is needed to establish the normal
      standards for children of all different ages.

PMID- 11821580
TI  - Epidemiology of paediatric cancer in Hong Kong, 1982 to 1991. Hong Kong Cancer
      Registry.
AB  - OBJECTIVE: To review the data of paediatric cancer that had been collected by the
      Hong Kong Cancer Registry from 1982 through 1991. DESIGN: Cross-sectional
      retrospective study. SETTING: Hong Kong. PATIENTS: Children aged 15 years or
      younger. MAIN OUTCOME MEASURES: The types of cancer were classified into 12
      diagnostic groups according to morphology (following the International
      Classification of Diseases for Oncology M-code). The incidences of the different
      types of cancer were obtained with reference to the Hong Kong population aged 15
      years or younger. Data collected between 1989 and 1991 were checked by paediatric
      oncologists from the Hong Kong Paediatric Haematology and Oncology Study Group.
      RESULTS: A total of 1756 cases of paediatric cancer were registered during the 10
      year period. The incidence of cancer was 144.3 new cases per million children.
      Leukaemia was the most common form of childhood cancer (40.0%), followed by brain
      tumour (16.3%), and lymphoma (10.8%). The relative frequencies of neuroblastoma
      (2.4%) and Wilms' tumour (3.5%) were lower than those reported from western
      countries. CONCLUSION: The incidences and types of paediatric cancer in Hong Kong
      are similar to those in western countries. Collaboration with paediatric oncology
      groups should provide more accurate information on the incidence and survival
      rates of children with cancer in Hong Kong.

PMID- 11821581
TI  - Chinese herbal formula XQ-9302: pilot study of its clinical and in vitro activity
      against human immunodeficiency virus.
AB  - OBJECTIVES: To evaluate the effectiveness of XQ-9302--a purified, precise mixture
      of 20 Chinese herbs--against infection with human immunodeficiency virus in vitro
      and in the clinic. DESIGN: In vitro cell culture assay, heavy metal content
      analysis, and pilot non-randomised clinical trial. SETTING: Drug rehabilitation
      centre and municipal surveillance centre, Shanghai, China. PATIENTS: Forty-eight
      patients who had various clinical histories, such as drug abuse, cancer, and
      infection with human immunodeficiency virus, participated in the clinical study.
      INTERVENTION: During the clinical trial, multiple 15-day courses of XQ-9302 10.8
      g/d were given to participants. MAIN OUTCOME MEASURES: CD4 count, P24 antigen
      level, level of antibody against human immunodeficiency virus, number of copies
      per millilitre of human immunodeficiency virus in the plasma (viral load), and
      any side effects. RESULTS: XQ-9302 protected cultured MT4 cells from infection
      with human immunodeficiency virus in vitro. Clinical tests showed that the herbal
      formula relieved the symptoms of acquired immunodeficiency syndrome and enhanced
      CD4 counts in patients infected by the human immunodeficiency virus. There were
      no observable side effects, even after taking the drug for several months. In
      three patients who had acquired immunodeficiency syndrome, treatment with XQ-9302
      reduced the magnitude of the viral load by more than 1 log. CONCLUSION: XQ-9302
      not only improves the immune function of patients infected with the human
      immunodeficiency virus, but also interrupts viral replication and slows the
      progression of the disease without detectable side effects. In addition, the
      heavy metal content of XQ-9302 is well within safety levels set by the Government
      of China.

PMID- 11821582
TI  - The diagnostic value of fine-needle aspiration cytology in the assessment of
      thyroid nodules: a retrospective 5-year analysis.
AB  - OBJECTIVE: To audit the diagnostic accuracy and value of fine-needle aspiration
      cytology in the assessment of thyroid nodules over a 5-year period. DESIGN:
      Retrospective study. SETTING: Private practice, Hong Kong. PATEINTS: The
      computerised records from cytological and histological examinations of all
      thyroid specimens submitted from 1993 through 1997 were studied; the 1236
      aspirates came from 1033 women and 175 men (gender was not specified in 28
      cases). MAIN OUTCOME MEASURES: Cytological reports were classified
      diagnostically, and histological and cytological correlations were determined.
      RESULTS: Of the 1236 aspirates, 113 (9.1%) were unsatisfactory; 1013 (82.0%),
      including cysts, were benign; and 110 (9.0%) were neoplastic or malignant.
      Histological follow-up was available for 149 cases; 13 were unsatisfactory for
      cytological diagnosis. Statistical analysis of the remaining 136 cases yielded
      the following results: sensitivity of fine-needle aspiration cytology, 56%;
      specificity, 90%; positive predictive value, 74%; negative predictive value, 80%;
      accuracy, 79%. These results were within the range of previously published
      values. The sensitivity was improved by combining clinical information: if
      nodules larger than 3-cm diameter were excised (despite a non-neoplastic
      aspiration cytology report), the sensitivity increased to 71% and the accuracy to
      84%. CONCLUSION: Fine-needle aspiration cytology is an effective screening test
      to help evaluate whether surgery is required in the management of thyroid
      nodules. False-positive and false-negative rates can be minimised by taking
      clinical and imaging data into consideration.

PMID- 11821583
TI  - Treatment of Helicobacter pylori infection.
AB  - The availability of clinic-based diagnostic tests means that screening for and
      the eradication of Helicobacter pylori can be done by primary care physicians.
      However, confusion still exists regarding indication and treatment regimens. It
      is universally accepted that patients with Helicobacter pylori infection and
      peptic ulcer disease require eradication therapy. But the benefits of
      Helicobacter pylori eradication in gastro-oesophageal reflux disease, non
      steroidal anti-inflammatory drug-related peptic ulceration, and non-ulcer
      dyspepsia remain unclear. There is no evidence that the elimination of
      Helicobacter pylori is beneficial for asymptomatic patients or in preventing
      gastric cancer. One-week triple therapy with a proton pump inhibitor or
      ranitidine bismuth citrate in combination with clarithromycin/metronidazole and
      amoxycillin is the recommended first-line treatment for Helicobacter pylori
      infection. Problems with patient compliance and the development of antibiotic
      resistance are the two most important factors to consider when choosing the
      treatment regimen. The optimal retreatment therapy for treatment failure is still
      unknown, and quadruple therapy is best reserved for these cases.

PMID- 11821584
TI  - Who should be treated for Helicobacter pylori infection?
AB  - Helicobacter pylori infection affects approximately half of the world's
      population. In Hong Kong, approximately 55% of the population is infected with
      this organism. But symptoms and clinical disease develop in only a minority of
      infected individuals during their lifetime. Treatment should thus be
      appropriately targeted. It is imperative that infected patients who have either a
      current or past history of peptic ulcer disease, with or without bleeding or a
      perforation complication, and those with low-grade gastric, mucosa-associated
      lymphoid tissue lymphoma should all have the organism eliminated. There is
      evidence that anti-Helicobacter pylori therapy reduces the recurrence of gastric
      cancer after the successful removal of early gastric cancer lesions. Patients
      with non-ulcer dyspepsia, particularly those with severe symptoms, should also be
      considered for a trial of eradication therapy. Whether or not eradication therapy
      should be given to those who require long-term non-steroidal anti-inflammatory
      drug therapy, but who do not have a history of peptic ulcer disease is still not
      decided. The use of prophylactic eradication to stop the development of gastric
      cancer or peptic ulceration in Helicobacter pylori-positive but asymptomatic
      individuals should be considered only in research settings.

PMID- 11821585
TI  - Helicobacter pylori infection: the reduced need for ulcer surgery.
AB  - The success of the eradication treatment for Helicobacter pylori in managing
      ulcer disease has further refined the indications for ulcer surgery. More
      patients are spared unnecessary surgery and its untoward sequelae. It is
      intriguing that surgery has been effective, given that Helicobacter pylori
      infection is the underlying culprit. Recent studies show that the prevalence of
      Helicobacter pylori infection remains high after a vagotomy but is more markedly
      reduced following a partial gastrectomy. Such a reduction may be due to the
      removal of distal stomach, which is the usual site of infection. In addition,
      bile appears to be bactericidal to Helicobacter pylori. The association between
      Helicobacter pylori infection and perforated duodenal ulcer has not been
      completely settled. A recent study demonstrates that male gender and positive
      Helicobacter pylori status are independent factors that are associated with
      recurrent duodenal ulcer after surgery for perforation. Hence, eradication
      therapy should be given to any patient who has a Helicobacter pylori infection,
      after surgery has been performed for perforated duodenal ulceration.

PMID- 11821586
TI  - The need for Helicobacter pylori eradication therapy in patients with peptic
      ulcer bleeding.
AB  - Peptic ulcer bleeding is an important complication of peptic ulceration. The
      condition carries significant morbidity and mortality despite advances in both
      endoscopic intervention techniques and pharmacological treatment. About one third
      of patients have a recurrence of bleeding within a few years of discharge. Before
      Helicobacter pylori was discovered, most of these patients were given maintenance
      therapy with antisecretory drugs or surgery to prevent a recurrence of the
      bleeding. Since the eradication of Helicobacter pylori reduces the recurrence of
      uncomplicated peptic ulcers, its eradication should also reduce peptic ulcer
      complications. The aim of this review is to discuss the value of eradicating
      Helicobacter pylori as part of the long-term management of bleeding peptic
      ulcers.

PMID- 11821587
TI  - Extragastroduodenal conditions associated with Helicobacter pylori infection.
AB  - Helicobacter pylori is a Gram-negative bacterium that is considered a causative
      agent of peptic ulcer disease, gastric lymphoma, and gastric carcinoma.
      Helicobacter pylori triggers an intense leucocyte infiltration of the gastric
      submucosa, an action which is mediated by pro-inflammatory cytokines. This
      pathogenetic mechanism is common to many other diseases and consequently,
      Helicobacter pylori seroprevalence has also been investigated in other diseases.
      It is now known that Helicobacter pylori seropositivity is associated with
      various cardiovascular, respiratory, extragastroduodenal digestive, neurological,
      dermatological, autoimmune, and growth disorders. Although the precise role of
      Helicobacter pylori is unknown in these diseases, the organism can be eradicated
      using simple and reliable drug regimens. The conditions associated with
      Helicobacter pylori seropositivity are highlighted in this article.

PMID- 11821588
TI  - Helicobacter pylori infection and gastric cancer.
AB  - Gastric cancer is the second most common fatal malignant neoplasm in the world.
      In mainland China, gastric cancer is now the second most common malignant
      neoplasm, while in Hong Kong the mortality rate ranked fourth of all cancers in
      1995. Dietary factors seem to be involved in gastric carcinogenesis, and beta
      carotene, selenium, and vitamin E (tocopherols) have been shown to help reduce
      gastric cancer mortality. Prospective case-control studies have shown an
      increased risk for the development of gastric cancer of between 2.8 and 6.0 among
      carriers of Helicobacter pylori. In addition, cagA-positive strains of
      Helicobacter pylori have been found to be associated with gastric cancer and
      duodenal ulceration. The exact role of Helicobacter pylori in gastric
      carcinogenesis is still being investigated. Helicobacter pylori eradication
      programmes to help prevent gastric cancer are being conducted in China and other
      parts of the world. In high-risk areas such as China, a combination approach that
      includes Helicobacter pylori eradication and dietary supplementation may be
      necessary.

PMID- 11821589
TI  - Chemotherapy for advanced non-small-cell lung cancer: role of paclitaxel and
      gemcitabine.
AB  - OBJECTIVE: To review the role of chemotherapy in advanced non-small-cell lung
      cancer, focusing on cisplatin-based regimens and two new drugs: paclitaxel and
      gemcitabine. DATA SOURCES: Medline search of the relevant English literature.
      STUDY SELECTION: Open and randomised comparative (phases II and III2) studies,
      and meta-analyses of cytotoxic drugs/regimens used to treat advanced non-small
      cell lung cancer. DATA EXTRACTION: The following factors were studied and
      compared: symptomatic response rates; tumour response rates: median survival time
      and 1-year survival rates; and side effects of cisplatin-, paclitaxel-, and
      gemcitabine-based regimens. DATA SYNTHESIS: Using cisplatin-based chemotherapy
      achieves significant relief of disease-related symptoms of advanced non-small
      cell lung cancer and a slight improvement in the median survival time (by
      approximately 1.5 months). New cytotoxic drugs that are effective and have good
      safety profiles include paclitaxel and gemcitabine. When used as single agents,
      these two drugs give response rates of approximately 25%. When used with
      cisplatin/carboplatin, response rates increase to 45% to 62% and 1-year survival
      rates increase to 40% to 60%. CONCLUSION: Paclitaxel, gemcitabine, and other
      drugs such as decetaxel and vinorelbine are promising new chemotherapeutic agents
      in the treatment of advanced non-small-cell lung cancer. These drugs can palliate
      disease symptoms and improve the median survival time. The optimal dose and
      treatment schedules, however, are yet to be defined.

PMID- 11821590
TI  - Physicians' practice patterns of treating Helicobacter pylori-associated peptic
      ulceration in public hospitals in Hong Kong: questionnaire survey. Coordinator
      Group of the Quality Assurance Subcommittee (Medicine), Hospital Authority, Hong
      Kong.
AB  - To survey the practice patterns of physicians in public hospitals in Hong Kong
      when treating Helicobacter pylori-associated peptic ulceration, the records of
      all patients from 22 medical units who had new peptic ulcers that had been
      diagnosed endoscopically during August 1996 were examined systematically. Patient
      data were entered on a one-page questionnaire. Five hundred and twelve patients
      with peptic ulceration were studied; 173 (34%) of whom had presented with gastro
      intestinal bleeding. The Helicobacter pylori status had been determined in 449
      (88%) patients, 280 (62%) of whom had subsequently tested positive for
      Helicobacter pylori. The biopsy urease test or histological examination had been
      performed for more than 95% of patients. Of 260 patients who had tested positive
      for Helicobacter pylori, 244 (94%) had received eradication therapy to eliminate
      this organism; a total of 291 patients, however, were receiving eradication
      therapy. The most commonly used regimen was proton pump inhibitor triple therapy
      (151 [52%] of 291 patients). Confirmation of the eradication of Helicobacter
      pylori had been planned for 152 (52%) of the 291 patients, whereas ulcer-healing
      drugs--mainly H2-receptor antagonists--had been prescribed for 87 (30%) patients
      after eradication. Curing Helicobacter pylori infection is therefore widely
      accepted in the management of peptic ulcer disease among physicians working in
      Hong Kong public hospitals.

PMID- 11821591
TI  - Treatment of palmar hyperhidrosis using tap water iontophoresis: local
      experience.
AB  - To evaluate the efficacy and safety of tap water iontophoresis in the treatment
      of severe idiopathic palmar hyperhidrosis, nine Chinese patients with severe
      palmar hyperhidrosis that had failed to respond to topical aluminium chloride
      were given 6 weeks' treatment with tap water iontophoresis at the Social Hygiene
      Service, Department of Health, Hong Kong. The reduction in sweat output was
      assessed objectively and subjectively. The mean objective reduction in sweat
      output was 49%, 51%, 26%, and 22% at week 3, 6, 10, and 12, respectively, since
      the start of treatment with tap water iontophoresis The mean subjective
      improvements were 43%, 59%, 30%, and 12% at week 3, 6,10, and 12, respectively.
      The side effects reported were all mild and transient. We conclude that tap water
      iontophoresis is a safe and useful treatment modality for palmar hyperhidrosis.

PMID- 11821592
TI  - Guidelines for the administration of hormone replacement therapy. The Hong Kong
      College of Obstetricians and Gynaecologists.
AB  - OBJECTIVES: To establish guidelines on the administration of hormone replacement
      therapy in Hong Kong for a primary audience of Fellows and Members of the Hong
      Kong College of Obstetricians and Gynaecologists and a secondary audience of all
      interested medical and paramedical personnel in Hong Kong. PARTICIPANTS: The
      Quality Assurance Committee established a consensus panel of four College Fellows
      who had expertise of treating menopausal women by giving hormone replacement
      therapy. All the panelists were qualified obstetricians and gynaecologists.
      EVIDENCE: The panelists drew their conclusions from the available scientific
      literature on hormone replacement therapy from Hong Kong and overseas. CONSENSUS
      PROCESS: The consensus reached within the panel was presented to the Quality
      Assurance Committee on 23 June 1998, and subsequently revised and presented three
      times. The final version was approved by the Quality Assurance Committee on 2
      March 1999 and the Council of the Hong Kong College of Obstetrics and Gynaecology
      on 11 March 1999. CONCLUSIONS: The administration of hormone replacement therapy
      is effective in reducing the severity and frequency of menopausal hot flushes and
      sweating. Therapy protects against osteoporosis and reduces the risk of
      cardiovascular disease. There is some evidence to suggest that treatment also
      protects against Alzheimer's disease and carcinoma of the colon. The most serious
      problem attributed to using hormone replacement therapy is the possible increase
      in the risk of breast cancer development; the exact risk is unknown. Side effects
      include unwanted bleeding and breast tenderness and sensitivity. The risks and
      benefits of using hormone replacement therapy should be explained to
      postmenopausal women so that they can make an informed decision about using this
      treatment.

PMID- 11821593
TI  - Delayed cholestatic hepatitis due to methimazole.
AB  - We report on a 71-year-old man who presented to the medical department of Our
      Lady of Maryknoll Hospital with progressive cholestatic hepatitis. Tests for
      hepatitis viral markers gave negative results and ultrasonography revealed no
      dilated bile ducts. Endoscopic retrograde cholangiopancreatography showed a
      normal biliary tree. The patient had completed a 5-month course of methimazole to
      treat thyrotoxicosis a few weeks before the onset of the jaundice. Methimazole
      was suspected to be the cause of the cholestatic hepatitis; this diagnosis was
      supported by the results from a liver biopsy. The presentation of the patient was
      unusual by virtue of the delayed onset and prolonged course of cholestasis.

PMID- 11821594
TI  - Splenic injury following colonoscopy.
AB  - Splenic injury following colonoscopy is rare but can be fatal and easily
      overlooked. A case of colonoscopic splenic injury is presented to highlight its
      potentially fatal complication. The risk factors, underlying mechanism, possible
      measures of prevention, diagnosis, and treatment are also discussed.

PMID- 11821596
TI  - Carotid stenting and angioplasty.

PMID- 11821595
TI  - Colchicine-induced myopathy and neuropathy.
AB  - Myopathy and neuropathy that have been induced by colchicine have been described
      only occasionally, although colchicine is a widely used drug. We describe a case
      of colchicine-induced myopathy and neuropathy in an 84-year-old woman who had
      renal impairment. Results from a muscle biopsy showed characteristic vacuolar
      myopathy and autophagic vacuoles. The cessation of medication resulted in a
      marked improvement of myopathy.

PMID- 11821600
TI  - A pilot study examining the frequency and quantity of gas embolization during
      operative hysteroscopy using a monopolar resectoscope.
AB  - STUDY OBJECTIVE: To assess baseline frequency of gas embolization during standard
      monopolar resectoscopic surgery. DESIGN: Prospective, nonrandomized,
      observational study (Canadian Task Force classification II-2). SETTING: Tertiary
      care medical center. PATIENTS: Eleven women and three controls. INTERVENTION:
      Operative hysteroscopy. MEASUREMENTS AND MAIN RESULTS: Echocardiography and serum
      studies were performed to detect bubble formation in the inferior vena cava,
      hepatic veins, and right heart. Gas bubbles were present in the hepatic veins or
      right heart in 10 patients and no controls. No patients had changes in
      coagulation profile and only one had clinical changes during surgery. CONCLUSION:
      Gas bubbles can been detected by echocardiography in most patients undergoing
      resectoscopic surgery in the uterus. Clinical significance may relate to anatomic
      variations as well as to gas bubble content and volume.

PMID- 11821601
TI  - Comparison of magnetic resonance imaging and transvaginal ultrasonography in
      diagnosing bladder endometriosis.
AB  - STUDY OBJECTIVE: To take recent progress in magnetic resonance imaging (MRI) into
      account to determine its accuracy compared with that of transvaginal
      ultrasonography (TVUS) in diagnosing bladder endometriosis. DESIGN: Retrospective
      analysis (Canadian Task Force classification II-2). SETTING: University
      affiliated hospital. PATIENTS: Twelve women with histologically proved bladder
      endometriosis. INTERVENTION: Magnetic resonance imaging with body and
      endocavitary coils and TVUS. MEASUREMENTS AND MAIN RESULTS: Although TVUS was
      normal in four patients, MRI enabled endometriotic lesions to be detected in all
      patients. Magnetic resonance imaging with endocavitary coil established the
      existence of deep infiltration in three patients when muscularis involvement was
      not visible with the body coil. In seven women MRI determined how far deep
      posterior endometriotic lesions extended, whereas with TVUS this was impossible
      to see. Conclusion. MRI had advantages over TVUS in diagnosing small lesions of
      associated posterior deep endometriotic lesions. The endocavitary coil gave
      better results than the phased-array coil for diagnosing deep infiltration. These
      results are important in that they help guide surgical management.

PMID- 11821602
TI  - Modified sonohysterography immediately after hysteroscopy in the diagnosis of
      submucous myoma.
AB  - STUDY OBJECTIVE: To report a new, convenient, inexpensive, office-based
      examination to evaluate submucous myomas before hysteroscopic myomectomy. DESIGN:
      Retrospective analysis (Canadian Task Force classification II-2). SETTING:
      University-affiliated teaching hospital. PATIENTS: One hundred seventy-nine
      consecutive women. INTERVENTION: Diagnostic flexible hysteroscopy and
      transvaginal ultrasonography. MEASUREMENTS AND MAIN RESULTS: Transvaginal
      ultrasonography was performed immediately after hysteroscopy. The size and depth
      of invasion of submucous myomas were clearly identified by retained fluid after
      hysteroscopy. Locations of myomas were as follows: anterior wall, 37 (20.7%);
      posterior wall, 52 (29.1%); lateral wall, 40 (22.3%); and fundus, 31 (17.3%); and
      multiple myomas, 19 (10.6%). Myomas with stalk were found in 101 patients (56.4%)
      and without stalk in 78 (43.6%). The mean myoma diameter was 2.95 +/- 2.12 cm and
      mean weight was 30.2 +/- 33.6 g. CONCLUSION: It is important to obtain details as
      to size and depth of invasion of submucous myomas before hysteroscopic
      myomectomy. Sonohysterography immediately after hysteroscopy is superior to
      traditional diagnostic methods.

PMID- 11821603
TI  - The effect of intraperitoneal ropivacaine on pain after laparoscopic excision of
      endometriosis.
AB  - STUDY OBJECTIVE: To compare the effects of ropivacaine and saline on pain after
      laparoscopic excision of endometriosis. DESIGN: Randomized, double-blind,
      controlled trial (Canadian Task Force classification I). SETTING: Women's
      hospital. PATIENTS: Ninety-three women undergoing excision of endometriosis.
      INTERVENTION: Laparoscopic excision of endometriosis, after which saline 100 mg
      (46 women) or ropivacaine 200 mg dissolved in 100 ml saline (47) was instilled
      intraperitoneally for postoperative analgesia. MEASUREMENTS AND MAIN RESULTS: No
      differences were seen between groups during the first 7 hours after surgery with
      respect to pain scores, analgesic requirements, postoperative nausea and
      vomiting, or time to discharge. CONCLUSION: We found no difference between
      ropivacaine and saline, instilled intraperitoneally, in their effects on pain
      after extensive excision of endometriosis.

PMID- 11821604
TI  - Characteristics and management of large bowel injury in laparoscopic-assisted
      vaginal hysterectomy.
AB  - STUDY OBJECTIVE: To review laparoscopic-assisted vaginal hysterectomies (LAVH)
      for large bowel injuries. DESIGN: Retrospective review (Canadian Task Force
      classification II-2). SETTING: University-affiliated hospital. PATIENTS: Two
      thousand eighty-four 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. Large bowel injuries occurred in
      six women (2.9/1000), only one of which was recognized postoperatively. Colostomy
      was performed in four patients, simple repair in one, and laparoscopic repair in
      one. All these patients were discharged without sequelae. CONCLUSION: In our
      experience, bowel injury during LAVH was not a common event.

PMID- 11821605
TI  - Endometrial adenocarcinoma encountered at the time of hysteroscopic endometrial
      ablation.
AB  - STUDY OBJECTIVE: To determine the diagnostic accuracy and possible role of
      treatment of hysteroscopic endometrial resection in women with abnormal uterine
      bleeding (AUB) diagnosed with endometrial adenocarcinoma. DESIGN: Retrospective
      analysis (Canadian Task Force classification II-2). SETTING: University
      affiliated center. PATIENTS: Thirteen women with AUB and eight with
      postmenopausal bleeding. INTERVENTION: Preablation endometrial office biopsy and
      hysteroscopic evaluation. MEASUREMENTS AND MAIN RESULTS: Preablation endometrial
      biopsy was inadequate, inconclusive, or difficult to obtain in these women, and
      endometrial cancer was found at the time of resectoscopic surgery. Total
      endomyometrial resection including the tubal ostia was completed in eight women
      (group 1) and partial resection in five (group 2). Endometrial adenocarcinoma was
      confirmed histologically in all patients. A small focus of cancer was found in
      only two women in group 1 after total resection; in one the procedure was
      performed 9 years earlier and in the other it was completed hastily after
      absorption of 800 ml of 1.5% glycine irrigation solution. In women in group 2
      malignancy was highly suspected and total resection was considered unwise.
      CONCLUSION: All patients were alive and well 0.5 to 9 years after hysterectomy,
      with no evidence of recurrent cancer.

PMID- 11821606
TI  - Clinical evaluation of laparoscopic-assisted radical vaginal hysterectomy with
      pelvic and/or paraaortic lymphadenectomy.
AB  - STUDY OBJECTIVE: To report our experience with radical laparoscopic-assisted
      vaginal hysterectomy (LAVH) with bilateral pelvic and/or paraaortic
      lymphadenectomy. DESIGN: Retrospective review (Canadian Task Force classification
      III). SETTING: University-affiliated hospital. PATIENTS: Fifty-two women with
      invasive carcinoma of the cervix, stage Ib1, smaller than 3 cm. INTERVENTION:
      Radical LAVH with pelvic and/or paraaortic lymphadenectomy. MEASUREMENTS AND MAIN
      RESULTS: Total operating time ranged from 230 to 650 minutes (mean 380 min).
      Major surgical complications were two cases of ureter injury, two cases of
      ureteral stricture, and one case of hematoma at the cannula site. Two cases were
      converted to laparotomy due to incomplete hemostasis of the uterine artery and
      obturator vein. The mean hemoglobin decrement was 1.7 g/dl the day after
      operation. Thirty patients received blood transfusion (mean 1.8 pints). Average
      numbers of pelvic and paraaortic lymph nodes removed were 27.7 (range 9-63) and
      22.1 (range 6-52), respectively. After surgery, patients passed gas in 2.2 days
      and self-voided in 18.4 days on average. One woman had pelvic recurrence at 26
      months after surgery. One died from brain metastasis 10 months after surgery.
      CONCLUSION: This technique is feasible for treatment of early cervical carcinoma.
      An experienced surgeon could shorten operating time and reduce complications.

PMID- 11821607
TI  - Total laparoscopic hysterectomy in the management of endometrial carcinoma.
AB  - STUDY OBJECTIVE: To compare total laparoscopic hysterectomy (TLH) with open
      hysterectomy in the management of endometrial carcinoma. DESIGN: Retrospective
      chart review (Canadian Task Force classification II-3). SETTING: Gynecologic
      cancer center. PATIENTS: All women with endometrial carcinoma managed between
      January 1, 1993, and June 30, 1999. INTERVENTIONS: Of 403 patients reviewed, in
      161 (40%) the surgical intention was laparoscopic management, in 230 (57%) the
      intention was open management, and in 12 (3%) it was vaginal hysterectomy. Total
      laparoscopic hysterectomy was successfully completed in 153 (95%) of the
      laparoscopic group. MEASUREMENTS AND MAIN RESULTS: Mean weight of women in the
      laparoscopic group (80.1 kg) was greater than that in the open group (73.3 kg, p
      = 0.002), and included 27 patients weighing over 100 kg (maximum individual
      weight 170 kg). Mean operating times were 138 minutes for laparoscopy and 121
      minutes for the open procedure (p = 0.002). Complications differed, with
      significantly more occurring in the open group (43%, 100) than in the
      laparoscopic group (17%, 27, p <0.00001). Mean postoperative hospital stay was
      significantly shorter for the laparoscopic group (4.3 days) than for the open
      group (8.5 days, p = 0.0001). Conclusion. TLH combined with laparoscopic surgical
      staging has many advantages over the open approach, especially in obese women.

PMID- 11821608
TI  - Comparison of two procedures for laparoscopic-assisted vaginal hysterectomy of
      large myomatous uteri.
AB  - STUDY OBJECTIVE: To evaluate whether laparoscopic bipolar coagulation of uterine
      vessels (LBCUV) and supracervical amputation improve laparoscopic-assisted
      vaginal hysterectomy (LAVH). DESIGN: Prospective, randomized, longitudinal study
      (Canadian Task Force classification II-1). SETTING: Private practice, university
      affiliated hospital. PATIENTS: Sixty-four women (age 31-52 yrs) with symptomatic
      myomatous uteri larger than 12 weeks on bimanual examination. INTERVENTIONS: LAVH
      with or without LBCUV and laparoscopic supracervical amputation followed by
      trachelectomy. MEASUREMENTS AND MAIN RESULTS: LBCUV and laparoscopic
      supracervical amputation followed by trachelectomy and removal of the specimen
      vaginally were performed successfully in 29 women (group A). Hysterectomy was
      performed successfully in 32 comparable patients (group B) with severing of the
      round ligament, ovarian ligament, or infundibulopelvic ligament, and preparation
      of the bladder flap in the laparoscopic phase, and severing of uterine vessels
      and cardinal-uterosacral ligament complex through the vagina. Average blood loss
      was 169.8 and 308.7 ml in groups A and B, respectively (p <0.05); average
      operating time was 126.4 and 152.8 minutes, respectively (p <0.05); hemoglobin
      decreased on average 0.9 and 1.7 g/100 ml, respectively (p <0.05). Conclusion.
      LBCUV and laparoscopic supracervical amputation followed by trachelectomy reduce
      operating time and blood loss in LAVH, and allow conversion of many abdominal
      procedures to laparoscopy.

PMID- 11821609
TI  - Squamous metaplasia of endometrium after uterine artery embolization for
      symptomatic leiomyomata.
AB  - Uterine artery embolization (UAE) is frequently performed for symptomatic
      leiomyomata. There have been no reports of squamous metaplasia of endometrium
      after such a procedure. Squamous metaplasia of endometrium is often associated
      with endometrial hyperplasia and carcinoma. In our patient the disorder was
      diagnosed after UAE. This is the second such case we have encountered. In view of
      the association of squamous metaplasia with endometrial hyperplasia and
      carcinoma, a history of recent UAE must be considered in evaluating a patient
      with this finding, particularly on a biopsy specimen.

PMID- 11821610
TI  - Atypical complex endometrial hyperplasia treated with the GyneLase system.
AB  - A 47-year-old premenopausal, para 1, gravida 1 woman complained of
      menometrorrhagia. She had no risk factors for endometrial hyperplasia or cancer,
      and office endometrial biopsy indicated focal, nonatypical endometrial
      hyperplasia. Seven months later the patient was scheduled for hysteroscopic
      endometrial resection. Instead she was treated by hysteroscopy, curettage, and
      the GyneLase system. The curetting indicated atypical, complex endometrial
      hyperplasia. The woman refused hysterectomy and salpingo-oophorectomy and
      adjunctive therapy with progesterone. She agreed to close surveillance and
      further treatment if she had any vaginal bleeding. At 13 months she remains
      amenorrheic, the endometrial echo is 2 mm, and follicle-stimulating hormone level
      is 63 IU/L. Based on the patient's amenorrhea and ultrasound uterine measurement,
      it is tempting to assume that GyneLase treatment may have cured her atypical
      hyperplasia. However, at this time, we have no evidence to substantiate this
      assumption.

PMID- 11821611
TI  - Early pregnancy uninterrupted by laparoscopic bipolar coagulation of uterine
      vessels.
AB  - Laparoscopic bipolar coagulation of uterine vessels (LBCUV) is reported to treat
      clinically symptomatic myomas that caused severe menorrhagia, but the viability
      of pregnancy after operation is unknown. A woman with clinically diagnosed
      uterine myomas, possibly with adenomyosis, had unexpected early pregnancy
      diagnosed at the time of LBCUV. The procedure resulted in improvement of
      menorrhagia to normal menstruation and reductions in the volume of both uterus
      and myomas. The intrauterine pregnancy was terminated at the woman's request.
      Pregnancy may be possible after LBCUV, although none has been reported.

PMID- 11821612
TI  - Laparoscopic surgery for omental pregnancy.
AB  - A 16-year-old girl underwent emergency laparoscopic surgery for what was thought
      to be hematoperitoneum secondary to extrauterine pregnancy. During the operation,
      omental pregnancy was diagnosed and treated by laparoscopy. According to
      Studiford's criterion, this case can be classified as a primary omental
      pregnancy. When performing laparoscopy for suspected tubal pregnancy with no
      visible pathologic changes on either tube, careful evaluation of the whole
      abdominal cavity is necessary so as not to overlook an abdominal pregnancy.

PMID- 11821613
TI  - Successful laparoscopic treatment of a ruptured primary ovarian pregnancy.
AB  - A 26-year-old woman had classic symptoms of primary ovarian pregnancy. Ultrasound
      examination disclosed a cystic mass surrounded by a complex mass that was
      compatible with hematoma in the pouch of Douglas, as well as an intrauterine
      device (IUD) displaced near the isthmic portion of the uterine cavity.
      Laparoscopy revealed a ruptured gestational sac in the cul-de-sac that was
      encapsulated by a hematoma originating from the right ovary. All deep-seated
      products of conception were excised from the ovary, and the IUD was removed.
      Treatment was successful and avoided more invasive intervention.

PMID- 11821614
TI  - Treatment of a torqued hematosalpinx in the thirteenth week of pregnancy using
      gasless laparoscopy.
AB  - Laparotomy and carbon dioxide laparoscopy are relatively traumatic and high-risk
      operations for patients. They may have negative effects on pregnancy, especially
      in advanced pregnancy. Gasless laparoscopy was performed on torqued hematosalpinx
      in a woman in the thirteenth week of pregnancy. After salpingectomy, the
      pregnancy proceeded normally.

PMID- 11821615
TI  - Rapid enlargement of uterine myomas after laparoscopic bipolar coagulation of
      uterine vessels.
AB  - Degenerative changes occur relatively frequently in uterine leiomyomas.
      Morphologic changes such as necrosis, hyalinization, and alterations in
      cellularity are described after uterine artery embolization. A modified method to
      interrupt the uterine blood supply is laparoscopic bipolar coagulation of uterine
      vessels (LBCUV). Although the success rate is good, occasional patients require
      hysterectomy because of complications or continuing symptoms. A woman with
      symptomatic myomas underwent LBCUV, but required hysterectomy due to rapid
      enlargement of myomas and intractable symptoms including pelvic pain and
      pressure, and acute urinary retention. The combination of degenerative and
      iatrogenic changes resulted in a histologic appearance resembling diffuse
      hyalinization and hydropic degeneration of the leiomyomas.

PMID- 11821616
TI  - Temporary ovarian suspension at laparoscopy for prevention of adhesions.
AB  - We performed an innovative technique of temporary ovarian suspension after
      operative laparoscopy for stage 3 and 4 endometriosis and evaluated the results
      in a retrospective study. Subjects were 20 women who underwent operative
      laparoscopy for infertility. Temporary ovarian suspension to the anterior
      abdominal wall was performed as the last step in the surgical procedure. It was
      done in an attempt to separate adhesiogenic surfaces during the initial phase of
      tissue healing (5-7 days). No complications occurred. After excluding patients
      who had additional infertility factors and/or were of advanced reproductive age,
      nine women tried to conceive spontaneously. Of these, five conceived (55%): three
      delivered, one pregnancy continues (80%), and one woman had an ectopic pregnancy
      (20%). Of the remaining 15 patients who failed to conceive spontaneously, 5 had a
      second-look laparoscopy. In four patients (80%), we found no evidence of
      recurrent adhesions. The remaining 20% had minimal adhesions. Temporary ovarian
      suspension appears to be simple and safe, and may be effective in preventing
      postoperative adhesions near the ovaries after operative laparoscopy for advanced
      endometriosis.

PMID- 11821617
TI  - Venous air and gas emboli in operative hysteroscopy.

PMID- 11821619
TI  - Hysterosalpingography.

PMID- 11821621
TI  - Laparoscopy versus laparotomy in pregnancy: a comparative study.

PMID- 11821622
TI  - Congestive heart failure: a house divided.

PMID- 11821623
TI  - The renin-angiotensin-aldosterone system and vascular remodeling.
AB  - Cardiac fibrosis can be accompanied initially by diastolic and ultimately by
      systolic ventricular dysfunction. Clinical and experimental evidence suggests a
      clear association between such adverse structural remodeling and activation of
      the circulating renin-angiotensin-aldosterone system (RAAS). Infusion of either
      of two RAAS effector hormones, angiotensin II and aldosterone, in rats evokes
      perivascular fibrosis of arteries and arterioles of the heart and kidneys.
      Additionally, increasing evidence indicates locally produced angiotensin II and
      aldosterone have important paracrine and autocrine actions that play a role in
      vascular remodeling. Both angiotensin II and aldosterone receptor antagonists
      have been shown to attenuate the appearance of cardiac and renal fibrosis.

PMID- 11821624
TI  - Impact of aldosterone on vascular pathophysiology.
AB  - The fact that spironolactone reduces deaths in cardiac failure suggests that
      aldosterone promotes cardiac death in heart failure, which begs the question:
      What are the mechanisms whereby it does this? The mechanisms whereby aldosterone
      promotes cardiac death are likely to be a combination of its production of
      endothelial dysfunction, myocardial fibrosis, and autonomic imbalance. It is
      quite possible that all three of these mechanisms actually stem from
      aldosterone's adverse effects on the endothelium. The term "aldosterone
      vasculopathy" has been coined to describe that the fundamentally adverse effect
      of aldosterone may well be on endothelial nitric oxide.

PMID- 11821625
TI  - Immune and neurohormonal pathways in chronic heart failure.
AB  - Chronic heart failure is a complex disorder with interactions among the
      cardiovascular, immune, and neurohormonal systems. The concept that the
      progression of heart failure is due to neurohormonal abnormalities has received
      the greatest attention to date, leading to substantial therapeutic benefits.
      Although many current therapies are also thought to exert a variety of
      immunologic effects, this has been much less studied. In this review, the authors
      discuss a number of interactions among immune pathways and neurohormonal
      abnormalities relevant to heart failure. Cytokines, in particular tumor necrosis
      factor-alpha, have tremendous interactive opportunities within a regulatory
      network of energy metabolism, immune function, and neuroendocrine and hormonal
      function. Inflammatory cytokines are known to contribute to the progression of
      heart failure, and have been related to patients' prognosis. Advanced heart
      failure can be considered a state of chronic (low-grade) inflammation, and there
      are many reasons to suggest that anticytokine therapy could be successful in
      these patients. These novel approaches are certainly not without some risk, and
      many of them are very expensive, which may limit their application to certain
      subgroups of patients. In the future, it may not be enough to monitor cardiac
      function alone. Rather, the immune and neurohormonal status of patients may also
      need to be included in the performance of a complete assessment.

PMID- 11821626
TI  - Natriuretic peptides and salt sensitivity: endocrine cardiorenal integration in
      heart failure.
AB  - Mammalian hearts contain a family of peptides with potent natriuretic, diuretic,
      and vasorelaxant actions. In addition to atrial natruretic peptide (ANP) and
      brain natriuretic peptide, recent studies in humans and animals have suggested
      that the N-terminal ANP prohormone fragment 31-67 may represent another adaptive
      mechanism to achieve body fluid homeostasis. Furthermore, these investigations
      have also suggested that via different mechanisms of action on target organisms,
      the C-terminal hormone ANP 99-126 and pro-ANP 31-67 may coordinate and contribute
      to the regulation of hemodynamic and renal function in pathophysiologic
      situations, such as heart failure.

PMID- 11821627
TI  - CHF: circulatory homeostasis gone awry.
AB  - The role of the renin-angiotensin-aldosterone system (RAAS) is integral to salt
      and water retention, particularly by the kidneys. Over time, positive sodium
      balance leads first to intra- and then to extravascular volume expansion, with
      subsequent symptomatic heart failure. This report examines the role of the RAAS
      in regulating a less well recognized component essential to circulatory
      homeostasis--central blood volume. The regulation of central blood volume draws
      on integrative cardiorenal physiology and a key role played by the RAAS in its
      regulation. In presenting insights into the role of the RAAS in regulating
      central blood volume, this review also addresses other sodium-retaining states
      with a predisposition to edema formation, such as cirrhosis and nephrosis.

PMID- 11821628
TI  - Nuggets, pearls, and vignettes of master heart failure clinicians. Part 3-
      Diagnostic studies: laboratory testing.

PMID- 11821629
TI  - Management of new-onset congestive heart failure in a patient with complex
      congenital heart disease.
AB  - The authors describe a 37-year-old African American female patient with
      congenital tricuspid stenosis, a secundum atrial septal defect, a ventricular
      septal defect, and subpulmonic stenosis whose only surgical intervention was a
      Glenn shunt procedure at the age of 11. She had been in reasonably good health
      for 26 years, but developed congestive heart failure. Her deteriorating clinical
      course was difficult to manage with only medical treatment, and cardiopulmonary
      transplantation is now being considered for the management of her complicated
      clinical condition.

PMID- 11821630
TI  - A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart
      failure.

PMID- 11821631
TI  - Randomized trial of an education and support intervention to prevent readmission
      of patients with heart failure.

PMID- 11821632
TI  - A "touch" of high blood pressure.

PMID- 11821633
TI  - The association between hypertension and other cardiovascular risk factors in
      young adult African Americans.
AB  - Hypertension is a major cause of cardiovascular disease in African Americans. The
      excess morbidity and mortality due to cardiovascular disease in African Americans
      compared to Caucasians is not well explained. The purpose of this study was to
      examine the association between hypertension and other cardiovascular risk
      factors in young adult African Americans. A risk factor scoring system was
      developed, based on national guidelines for obesity, smoking, cholesterol levels,
      glucose tolerance, and blood pressure. Data from a previously studied cohort of
      206 women and 117 men were analyzed for the association of hypertension with
      other risk factors. Among women, risk factor intensification is due to impaired
      glucose tolerance and obesity. Among men, intensification appears to be related
      to all major risk factor categories. These findings indicate that among
      hypertensive African Americans there is an amplification of other risk factors.
      The data also support the clinical management of multiple risk factors as well as
      the achievement of blood pressure control.

PMID- 11821634
TI  - Psychological characteristics and responses to antihypertensive drug therapy.
AB  - The objective of this study was to explore the relationship between psychological
      characteristics and responses to antihypertensive drug therapy. Twenty-two
      hypertensive subjects underwent psychological evaluation and treatment with 1) a
      diuretic, hydrochlorothiazide (HCTZ); 2) an angiotensin-converting enzyme (ACE)
      inhibitor, quinapril; and 3) combined alpha + beta blockade (doxazosin +
      betaxolol). Anger-Out scores on the State-Trait Anger Expression Inventory were
      positively correlated with the HCTZ-induced fall in systolic blood pressure
      (p<0.01); Anger-In was negatively correlated with the quinapril-induced fall in
      systolic pressure (p<0.05). The target systolic blood pressure (130 mm Hg) was
      achieved with either HCTZ or quinapril in 79% of subjects without, vs. 25% of
      subjects with, childhood trauma (p=0.03). Responses to doxazosin + betaxolol were
      not correlated with psychological characteristics. The authors conclude that both
      inhibited anger expression and childhood trauma are associated with reduced
      response to a diuretic or ACE inhibitor. Combined alpha/beta blockade may be
      preferable to an ACE inhibitor or diuretic in treating selected hypertensive
      patients. Further studies should include examination of psychological factors in
      terms of the response to combined ACE inhibitor + diuretic therapy.

PMID- 11821635
TI  - Factors influencing the systolic blood pressure response to drug therapy.
AB  - In the early stage of hypertension, diastolic blood pressure has greater
      prognostic importance, but in the elderly, systolic blood pressure is the most
      important marker of cardiovascular complications. Therefore, the need for more
      strict control of this component of blood pressure must be reconsidered. The
      benefit obtained in different studies in the elderly suggests that the treatment
      of isolated systolic hypertension is associated with a reduction in overall
      cardiovascular mortality of 22%, in coronary heart disease mortality of 26%, and
      in stroke mortality of 33%. However, a higher percentage of patients (73%) attain
      the diastolic goal of <90 mm Hg, while only 34% have systolic pressure reduced to
      <140 mm Hg. In a review of randomized trials comparing at least four different
      antihypertensive drugs, significant differences in systolic blood pressure
      reduction have not been demonstrated, except in black populations, in whom
      calcium channel blockers and diuretics seem to be more effective. In patients
      with isolated systolic hypertension, data are inconclusive, but calcium channel
      blockers and diuretics appear to lower blood pressure to a greater degree than do
      other antihypertensive drugs. Two main predictors of difficulty in controlling
      systolic blood pressure are the baseline blood pressure and the presence of
      diabetes. Other predictors are the duration of arterial hypertension, older age,
      the presence of target organ damage and associated clinical conditions
      (myocardial infarction, stroke, chronic renal failure), and an elevated serum
      uric acid level. It appears that the profile of patients with a poorer
      therapeutic response includes a greater severity of hypertension and/or the
      presence of cardiovascular disease.

PMID- 11821636
TI  - Salt intake, endothelial dysfunction, and salt-sensitive hypertension.
AB  - Numerous epidemiologic and clinical studies have demonstrated a clear
      relationship between high salt intake and blood pressure. However, the mechanisms
      of a salt-induced increase in blood pressure--a phenomenon known as salt
      sensitivity--and the heterogeneity of this effect are far from being completely
      understood. Endothelial dysfunction, and especially the nitric oxide system, is
      implicated in both experimental and clinical hypertension. Animal studies
      indicate that endogenous nitric oxide plays an important role in renal
      hemodynamics and sodium homeostasis, inducing renal vasodilation and natriuresis.
      Studies of essential hypertensive patients have also suggested that both high
      salt intake and salt sensitivity are associated with impaired endothelial
      function. Although there are many hypotheses concerning the nature of salt
      sensitivity, clinical data indicate that salt-sensitive patients may be unable to
      up-regulate the production of nitric oxide in response to salt intake. This
      endothelial dysfunction, which is more frequent in salt-sensitive than in salt
      resistant essential hypertensive patients, may partially explain the blood
      pressure increase in response to salt intake and may underlie the more pronounced
      target organ damage and cardiovascular risk in salt-sensitive patients.

PMID- 11821637
TI  - Blood pressure reduction in those with cerebrovascular disease prevents secondary
      stroke.

PMID- 11821638
TI  - Estrogen replacement does not prevent recurrent stroke or death in postmenopausal
      women after an ischemic stroke.

PMID- 11821639
TI  - ACE inhibitor-associated cough lessened with iron supplementation.

PMID- 11821640
TI  - Most antihypertensives have similar efficacy and safety: a meta-analysis.

PMID- 11821641
TI  - Type 2 diabetes: RENAAL and IDNT--the emergence of new treatment options.
AB  - The Reduction in End Points in NIDDM with the Angiotensin II Antagonist Losartan
      (RENAAL) study and the Irbesartan Diabetic Nephropathy Trial (IDNT) are two
      recently reported trials with hard end points, conducted in patients in advanced
      stages of diabetic nephropathy. Two other studies--the Irbesartan
      Microalbuminuria Study (IRMA)-2 and the Microalbuminuria Reduction with Valsartan
      study (MARVAL)--were trials conducted in patients with type 2 diabetes with
      microalbuminuria, a cardiovascular risk factor associated with early-stage
      diabetic nephropathy. These trials all had a common theme--that is, does an
      angiotensin receptor blocker (ARB) interfere with the natural history of diabetic
      nephropathy in a blood pressure-independent fashion? Without question, the
      results of these trials legitimatize the use of the ARB class in forestalling the
      deterioration in renal function, which is almost inevitable in the patient with
      untreated diabetic nephropathy. These data can now be added to the vast array of
      evidence supporting angiotensin-converting enzyme (ACE) inhibitor use in patients
      with nephropathy associated with type 1 diabetes. It now appears a safe
      conclusion that the patient with diabetic nephropathy should receive therapy with
      an agent that interrupts the renin-angiotensin system. These studies have not
      resolved the question as to whether an ACE inhibitor or an ARB is the preferred
      agent in people with nephropathy from type 1 diabetes, though the optimal doses
      of these drugs remain to be determined. Head-to-head studies comparing ACE
      inhibitors to ARBs in diabetic nephropathy are not likely to occur, so it is
      unlikely that comparable information will be forthcoming with ACE inhibitors. An
      evidence-based therapeutic approach derived from these trials would argue for
      ARBs to be the foundation of therapy in the patient with type 2 diabetes and
      nephropathy.

PMID- 11821642
TI  - Terror strikes the heart--September 11, 2001.

PMID- 11821643
TI  - Refractory or resistant hypertension.

PMID- 11821644
TI  - Pheochromocytoma.
AB  - Pheochromocytoma, a relatively rare (<0.05% of hypertensives), catecholamine
      secreting tumor, is almost always lethal unless recognized and appropriately
      treated. Clinical and biochemical manifestations are mainly caused by excess
      circulating catecholamines and hypertension. Manifestations mimic many
      conditions, which may result in erroneous diagnoses and improper treatment.
      Sustained or paroxysmal hypertension associated with headaches, sweating, or
      palpitations, occurs in 95% of patients, but at least 5% are normotensive. All
      patients with manifestations of hypercatecholaminemia or coexisting neoplasms
      should be investigated for pheochromocytoma. Plasma free metanephrines and
      fractionated urinary metanephrines are the most sensitive (about 100%) chemical
      tests for diagnosing sporadic and familial pheochromocytomas; plasma and urinary
      catecholamines and total metanephrines are fairly sensitive for identifying
      sporadic cases but are less sensitive for familial tumors. The clonidine
      suppression test helps exclude other conditions that may elevate plasma and
      urinary catecholamines and their metabolites. Magnetic resonance imaging is more
      sensitive than computed tomography for localizing pheochromocytomas; iodine-131
      metaiodobenzylguanidine (131I-MIBG) tumor uptake confers specificity. Surgical
      resection is successful in 90% of cases, but 10% of tumors are malignant.
      Pheochromocytomas <5 cm in diameter can be removed laparoscopically; larger
      tumors should be removed by open surgery. Drug treatment prior to and during
      surgery is mandatory; drug treatment, chemotherapy, and radiation therapy are
      used to treat malignant lesions.

PMID- 11821645
TI  - Tracleer (bosentan).

PMID- 11821649
TI  - Structural requirements of alkanol interaction sites on human alpha 2 beta 4
      neuronal nicotinic acetylcholine receptors expressed in Xenopus oocytes: effects
      of linear and branched-chain alkanols.
AB  - BACKGROUND: Nicotine and alcohol are both drugs of abuse that are frequently used
      concurrently, but little is known about the interactions between these agents at
      the molecular level. The neuronal subgroup of nicotinic acetylcholine receptors
      (nAChRs) are members of a neurotransmitter-gated ion channel superfamily and have
      been used extensively to characterize the interactions of ethanol with these
      channels. Previous work has shown that both the direction and the magnitude of
      the modulatory effects of n-alcohols and several fluorinated analogs on nAChRs
      can be predicted based upon the molecular volume of the alkanol. However, size
      (molecular volume) is only one of several determinants of binding-site
      interactions; shape and flexibility of the interacting ligand and/or the site
      itself (i.e., structural constraints) and alkanol hydrophobicity are also likely
      to be involved. METHODS: Two-electrode voltage-clamp electrophysiology was used
      to investigate the effects of alkanols on the alpha2beta4 human neuronal
      nicotinic acetylcholine receptor ectopically expressed in Xenopus oocytes.
      RESULTS: ACh-induced currents mediated by alpha2beta4 nAChRs were potentiated by
      1- and 2-propanol, whereas 1-pentanol and several branched-chain pentanol isomers
      only inhibited channel activity. 1-Butanol had a biphasic concentration-response
      curve, producing a nearly 2-fold increase in current at lower concentrations and
      >50% inhibition at higher concentrations. Other four-carbon alcohols such as 2
      butanol and 2-methyl-1-propanol also facilitated responses at lower
      concentrations and inhibited at higher concentrations, whereas 2-butene-1-ol and
      2-methyl-2-propanol only inhibited responses. The effects of these alkanols on
      ACh responses were the result of changes in both the potency as well as the
      efficacy of ACh at these receptors. CONCLUSIONS: Although molecular volume and
      hydrophobicity both correlate well with the potencies of linear alkanols in
      modulating the activity of alpha2beta4 nAChRs, these relationships break down
      almost completely when comparing the structural isomers of these agents. The
      structure of the interacting alkanol significantly affects the potency and
      efficacy of alkanols at the nAChR, and this occurs independently of differences
      in molecular volume and hydrophobicity.

PMID- 11821648
TI  - Gene coding variant in Cas1 between the C57BL/6J and DBA/2J inbred mouse strains:
      linkage to a QTL for ethanol-induced locomotor activation.
AB  - BACKGROUND: Among some (e.g., DBA/2J or D2) but not all (C57BL/6J or B6) inbred
      strains of mice, ethanol has a marked psychostimulant effect. Intercrosses formed
      from the D2 and B6 strains have been used to detect quantitative trait loci
      (QTLs) for this phenotype. The major QTL is found at the mid-region of chromosome
      2 (Demarest et al., 1999). This QTL has also been detected in heterogeneous stock
      mice (Demarest et al., 2001). A potential candidate gene in this region is Cas1,
      which codes for catalase. The current studies were conducted to determine (a) if
      there was difference in the open reading frame (ORF) of Cas1 between the D2 and
      B6 strains; (b) if a difference was found, was it likely that the difference had
      functional effects; and (c) if it could be established that Cas1 meets the
      criteria for QTL to gene. METHODS: The open reading frame (ORF) of Cas1 was
      sequenced in both the D2 and B6 mouse strains. A single polymorphism was found
      between the strains (see below); the strain distribution pattern for this
      polymorphism was determined in the 36 strains of the B6XD2 (BXD) recombinant
      inbred (RI) series. These data were used to map the position of Cas1 as described
      by Cudmore et al. (1999). RESULTS: The only difference between the D2 and B6
      strains in the coding region was found at #349, G->A. This will result in a
      difference in the amino acid sequence between the strains at amino acid #117
      alanine is found in the D2 strain while threonine is found in the B6 strain. The
      RI strain distribution pattern for this polymorphism was used to determine the
      relative placement of Cas1. The estimate suggests that Cas1 is flanked by D2Mit12
      and D2Mit43 and relative to D2Mit94 (which was set at 47 cM), Cas1 is located at
      approximately 57 cM, confirming previous estimates (see www.jax.org).
      CONCLUSIONS: Pharmacological data (Correa et al., 2001) strongly support the idea
      that Cas1 meets the criteria for QTL to gene. However, based on the mapping data,
      Cas1 is clearly not included in the QTL for heterogeneous stock mice. Finally,
      other genetic data suggest that the polymorphism is not sufficient to generate
      the QTL.

PMID- 11821650
TI  - Inverse genetic association between alcohol preference and severity of alcohol
      withdrawal in two sets of rat lines selected for the same phenotype.
AB  - BACKGROUND: The purpose of the present study was to determine whether alcohol
      naive rats selectively bred for alcohol preference or nonpreference differ in
      alcohol withdrawal severity using two sets of rat lines selectively bred for the
      same phenotype. METHODS: Alcohol-naive male rats from the high alcohol drinking
      (HAD1) and low alcohol drinking (LAD1) rat lines and from the alcohol preferring
      (P) and nonpreferring (NP) rat lines received an intragastric infusion of alcohol
      (4.0 g/20.3 ml/kg; 25% v/v) or an equal volume of water once a day for 10
      consecutive days. Alcohol withdrawal severity was assessed at using a behavioral
      rating scale and a radiant heat assay measured analgesia at 10, 12, 14, 16, 18,
      and 24 hrs following infusion of alcohol or water on days 1, 5, and 10 of
      treatment. RESULTS: Data were analyzed using body weight as a co-factor to
      correct for differences in body weight between the HAD1/LAD1 and P/NP lines.
      Acute (1 day) but not repeated alcohol treatment (5 or 10 days) produced mild
      behavioral signs of withdrawal in LAD1 but not in HAD1 rats. HAD1 and LAD1 rats
      showed alcohol-induced analgesia after 1 and 5 days of alcohol treatment that
      disappeared by day 10 in both lines. Repeated alcohol treatment (5 days) produced
      mild behavioral signs of withdrawal in NP but not in P rats. Neither P nor NP
      rats showed alcohol-induced analgesia after 1, 5, or 10 days of alcohol
      treatment. CONCLUSIONS: An inverse genetic association was found between alcohol
      preference and severity of alcohol withdrawal in two sets of rat lines selected
      for the same phenotype. The pattern of alcohol withdrawal that emerged over the
      course of the 10 days of alcohol treatment differed between the two lines
      selected for low alcohol drinking (LAD1 and NP), suggesting that unique sets of
      genes may influence alcohol withdrawal severity in the two lines.

PMID- 11821651
TI  - The Alcohol Use Disorders Identification Test and carbohydrate-deficient
      transferrin in alcohol-related sickness absence.
AB  - BACKGROUND: Previous studies have shown that elevated, risky levels of alcohol
      consumption may lead to higher rates of sickness absence. However, no studies
      have examined the Alcohol Use Disorders Identification Test (AUDIT) or serum
      carbohydrate-deficient transferrin (CDT) in relation to sickness absence in the
      workplace. The purpose of this study was to examine the relationship between sick
      days, 12 months before screening, and the AUDIT and CDT (CDTect kit). Serum gamma
      glutamyltransferase also was used for comparison. METHOD: The study was carried
      out over 36 months in a large workplace and formed part of an ongoing controlled
      study. In conjunction with a routine health examination, employees were offered
      the opportunity to undergo an alcohol screening. Absence data were obtained from
      the company payroll system, and sickness absence was analyzed by using a three
      ordinal level cumulative logistic model on the number of sick-days. Odds ratios
      (OR) and 95% confidence intervals (CI) are reported. RESULTS: Of the 989 subjects
      who participated in the study, 193 (19.5%) screened positive in relation to
      either the AUDIT (>or=8 points) or CDT (<20 units/liter for men, and <27
      units/liter for women), or both. Employees who screened positive with the AUDIT
      had a significantly higher proportion of sick-days (p = 0.047) compared with
      those who screened negative (OR = 1.4, CI 1.0-1.9). Neither long, continuous
      periods of sickness absence nor absence on Mondays or Fridays gave a clear
      indication of individuals who screened positive on the AUDIT or CDT test.
      CONCLUSION: Our data indicate that individuals with moderately elevated or risky
      levels of alcohol consumption show an increase in sick-days. Accordingly,
      workplaces have a good reason for using a more systematic approach to alcohol
      screening in routine workplace health examinations.

PMID- 11821652
TI  - Brief physician advice for problem drinkers: long-term efficacy and benefit-cost
      analysis.
AB  - BACKGROUND: This report describes the 48-month efficacy and benefit-cost analysis
      of Project TrEAT (Trial for Early Alcohol Treatment), a randomized controlled
      trial of brief physician advice for the treatment of problem drinking. METHODS:
      Four hundred eighty-two men and 292 women, ages 18-65, were randomly assigned to
      a control (n = 382) or intervention (n = 392) group. The intervention consisted
      of two physician visits and two nurse follow-up phone calls. Intervention
      components included a review of normative drinking, patient-specific alcohol
      effects, a worksheet on drinking cues, drinking diary cards, and a drinking
      agreement in the form of a prescription. RESULTS: Subjects in the treatment group
      exhibited significant reductions (p < 0.01) in 7-day alcohol use, number of binge
      drinking episodes, and frequency of excessive drinking as compared with the
      control group. The effect occurred within 6 months of the intervention and was
      maintained over the 48-month follow-up period. The treatment sample also
      experienced fewer days of hospitalization (p = 0.05) and fewer emergency
      department visits (p = 0.08). Seven deaths occurred in the control group and
      three in the treatment group. The benefit-cost analysis suggests a 43,000 dollars
      reduction in future health care costs for every 10,000 dollars invested in early
      intervention. The benefit-cost ratio increases when including the societal
      benefits of fewer motor vehicle events and crimes. CONCLUSIONS: The long-term
      follow-up of Project TrEAT provides the first direct evidence that brief
      physician advice is associated with sustained reductions in alcohol use, health
      care utilization, motor vehicle events, and associated costs. The report suggests
      that a patient's personal physician can successfully treat alcohol problems and
      endorses the implementation of alcohol screening and brief intervention in the US
      health care system.

PMID- 11821653
TI  - Alcohol consumption attenuates febrile responses to lipopolysaccharide and
      interleukin-1 beta in male rats.
AB  - BACKGROUND: Chronic and acute alcohol use exert profound modulatory effects on
      the immune system which manifest as impaired host defense against infections. An
      important feature of this response is the interaction between the immune and the
      central nervous systems. This study investigated the effects of 14 days of
      alcohol exposure on cytokine-mediated neuroimmune interactions that affect the
      febrile component of the host-defense response. METHODS: Adult male rats were fed
      a liquid diet containing ethanol (EtOH, 5% w/v) for 14 days. Pair-fed and normal
      chow- and water-fed rats served as controls. Continuous biotelemetric recordings
      of body temperature and locomotor activity commencing after 14 days of EtOH
      feeding were used to determine the effects of chronic EtOH on the circadian
      pattern of temperature and activity, on the febrile response to intraperitoneal
      (ip) administration of lipopolysaccharide (LPS) and interleukin (IL)-1beta, and
      on fever induced by IL-1beta administered intracerebroventricularly. We also
      examined the effects of EtOH consumption on LPS-induced hypothalamic production
      of the pyrogenic cytokines IL-1beta and tumor necrosis factor-alpha (TNFalpha)
      and on the blood levels of IL-1beta, TNFalpha, IL-6, adrenocorticotropin, and
      corticosterone at 2, 4, and 6 hr after ip LPS. RESULTS: Fourteen days of EtOH
      consumption blunted the circadian increases in temperature and activity that
      normally occur in the dark phase of the light/dark cycle without affecting light
      phase temperature or activity. EtOH consumption attenuated fever induced by LPS
      or IL-1beta administered ip during the light phase and significantly reduced
      hypothalamic production of IL-1beta. LPS-induced increases in hypothalamic
      TNFalpha and blood cytokines, adrenocorticotropin, and corticosterone were
      unaffected. Central administration of IL-1beta produced a normal febrile response
      in chronic-EtOH rats. CONCLUSIONS: The attenuated LPS- and IL-1beta-induced
      febrile responses in EtOH-consuming rats and the corresponding deficit in
      hypothalamic production of IL-1beta suggest that alcohol may impair IL-1beta
      mediated neuroimmune communication.

PMID- 11821654
TI  - Fetal and maternal thyroid hormone responses to ethanol exposure during the third
      trimester equivalent of gestation in sheep.
AB  - BACKGROUND: Abnormal thyroid hormone system function in the mother or fetus
      during pregnancy can result in brain defects, some of which resemble those found
      in children with fetal alcohol syndrome. It has been hypothesized that ethanol
      may act to mediate alcohol-related birth defects in part by altering thyroid
      hormone system function. We investigated whether a binge pattern of maternal
      ethanol consumption over the last trimester equivalent of gestation in sheep
      results in an alteration in fetal or maternal thyroid function. METHODS: Pregnant
      ewes received saline or ethanol beginning on day 109 of gestation (term, 145
      days) for three consecutive days per week followed by 4 days without exposure.
      The fetuses were surgically instrumented on day 113, and experiments were
      performed on days 118 or 132. Fetal and maternal blood samples were collected,
      and plasma tri-iodothyronine (T3), thyroxine (T4), and free T4 concentrations
      were measured. RESULTS: Fetal T3 and T4 on day 118, fetal T3 on day 132, and
      maternal T3 on day 132 were lower in response to ethanol. Fetal and maternal free
      T4 and maternal T4 did not change in response to ethanol. Fetal thymus and
      adrenal weights were reduced in response to ethanol. CONCLUSIONS: We conclude
      that, in sheep, maternal ethanol exposure during the third trimester equivalent
      resulting in blood ethanol concentrations that are commonly achieved by ethanol
      abusers decreases circulating thyroid hormone concentrations in the mother and
      fetus and fetal thyroid and thymus mass.

PMID- 11821655
TI  - Influence of alcohol consumption on serum immunoglobulin E levels in atopic and
      nonatopic adults.
AB  - BACKGROUND: Total and specific serum immunoglobulin E (IgE) are routinely used as
      diagnostic tools in allergy clinics. Several studies have demonstrated an
      increase of total serum IgE concentrations in alcoholics, but the possible
      influence of lower quantities of ethanol intake on serum IgE values has not been
      fully evaluated. This study was aimed at analyzing the influence of alcohol
      intake on both total and specific serum IgE concentrations in patients studied in
      an allergy clinic. METHODS: A total of 460 patients were included in the study.
      According to skin-prick tests to common aeroallergens, 325 were classified as
      atopics and 135 as nonatopics. Most atopic patients (253; 78%) were allergic to
      mites. Alcohol consumption was recorded as the number of standard (10-g) drinking
      units regularly consumed per week. Two hundred subjects (43%) were abstainers,
      and 260 (57%) were regular consumers of a median of 30 g of alcohol per week.
      Total serum IgE was measured in all patients by latex-enhanced nephelometry.
      Serum-specific IgE was assayed by fluoroenzymeimmunoassay. RESULTS: Total serum
      IgE increased along with ethanol consumption. On multivariate analysis, regular
      alcohol consumption greater than 70 g per week was associated with increased
      total serum IgE levels, even when adjusting for age, sex, atopy, and smoking.
      Among house-dust mite-allergic patients, specific serum IgE values against the
      house dust mite Dermatophagoides pteronyssinus were higher in regular alcohol
      consumers than in abstainers. This difference was not observed among patients
      allergic to grass pollen (Lolium perenne). CONCLUSIONS: Alcohol consumption, even
      in moderate quantities, is associated with increased total and specific IgE
      concentrations in subjects studied in an allergy clinic. Alcohol intake should be
      taken into account in epidemiological studies of total serum IgE levels.

PMID- 11821656
TI  - Acute alcohol intoxication suppresses the CXC chemokine response during
      endotoxemia.
AB  - BACKGROUND: CXC chemokines play an important role in host defense against
      infections. Alcohol is a frequently abused drug that inhibits numerous immune
      functions of the host. This study investigated the effects of alcohol on CXC
      chemokine macrophage inflammatory protein-2 (MIP-2) and cytokine-induced
      neutrophil chemoattractant (CINC) responses in rats challenged with intravenous
      lipopolysaccharide (LPS). METHODS: Acute ethanol intoxication was induced by an
      intraperitoneal injection of 20% alcohol (5.5 g/kg). Thirty minutes thereafter,
      LPS (500 microg/kg) was administered intravenously. In another set of
      experiments, rats were intravenously administered an anti-tumor necrosis factor
      alpha (TNFalpha) neutralizing antibody (10 mg per rat) 2 hr before the LPS
      challenge. RESULTS: At 1 and 2 hr after the LPS challenge, MIP-2, CINC, and
      TNFalpha concentrations in the plasma were significantly increased. Alcohol
      intoxication suppressed the MIP-2, CINC, and TNFalpha responses in the
      bloodstream during endotoxemia. Alcohol also suppressed the increase in plasma
      chemotactic activity and polymorphonuclear leukocyte adhesion molecule expression
      in rats with endotoxemia. MIP-2 and CINC messenger RNA (mRNA) expression was
      significantly increased 1 hr after endotoxemia in the lung, liver, and spleen.
      Alcohol suppressed the up-regulation of MIP-2 mRNA expression in all of these
      organs and CINC mRNA expression in the lungs of rats with endotoxemia. TNFalpha
      neutralization minimally inhibited plasma CINC and MIP-2 responses during
      endotoxemia and did not suppress the increase in plasma chemotactic activity.
      CONCLUSIONS: These results show that alcohol suppresses the systemic CXC
      chemokine response to LPS, which is not primarily mediated by ethanol-induced
      suppression of TNFalpha. This disruption of host-defense function may serve as
      one mechanism underlying the increased risk of infectious diseases in hosts who
      abuse alcohol.

PMID- 11821657
TI  - A role for interleukin-10 in alcohol-induced liver sensitization to bacterial
      lipopolysaccharide.
AB  - BACKGROUND: Proinflammatory cytokines play an important role in alcohol-induced
      liver injury. The role of anti-inflammatory cytokines in the initiation and
      progression of alcoholic liver disease has received little attention. This study
      tested the hypothesis that an imbalance exists between pro- and anti-inflammatory
      cytokines in the liver during chronic exposure to alcohol. Alcohol exposure
      results in predominantly proinflammatory cytokine secretion and liver injury.
      METHODS: IL-10 knock-out and their C57BL/6J counterpart wild-type mice were fed
      alcohol in drinking water for 7 weeks. At the end of alcohol feeding, Gram
      negative bacterial lipopolysaccharide (LPS) was administered, and the animals
      were killed after 3 and 8 hr. Liver histology, plasma alanine aminotransferase
      and aspartate aminotransferase activity, tumor necrosis factor-alpha, interleukin
      (IL)-1beta and IL-10 levels, and liver cytokine messenger RNA levels were
      measured. RESULTS: Alcohol feeding and LPS treatment did not change plasma enzyme
      activity levels in wild-type mice. In the IL-10 knock-out mice, LPS alone
      increased aspartate aminotransferase and alanine aminotransferase enzyme
      activity, and this was potentiated by alcohol. Alcohol induced liver steatosis in
      both wild-type and knock-out mice. LPS markedly enhanced the histological effects
      further, especially in the knock-out mice, with the emergence of focal necrosis,
      polymorphonuclear infiltration, and microabscesses in the liver. Plasma tumor
      necrosis factor-alpha and IL-1beta levels were not affected by alcohol alone.
      Proinflammatory cytokine levels were increased by LPS and further enhanced by
      alcohol treatment, particularly in the IL-10 knock-out mice. IL-10 plasma levels
      in the wild-type animals were down-regulated by alcohol. Changes in liver
      cytokine messenger RNA paralleled those seen in plasma cytokine levels.
      CONCLUSIONS: Alcohol-induced liver sensitization to LPS in wild-type mice may
      involve down-regulation of IL-10. This anti-inflammatory cytokine, known for its
      hepatoprotective effects, is secreted simultaneously with proinflammatory
      cytokines. IL-10 may also limit alcohol-induced liver damage by counteracting the
      effects of proinflammatory cytokines.

PMID- 11821658
TI  - Selective and enduring deficits in spatial learning after limited neonatal binge
      alcohol exposure in male rats.
AB  - BACKGROUND: In rats, heavy bingelike alcohol exposure during the neonatal brain
      growth spurt [postnatal days (PD) 4-9] can impair development of spatial
      learning. This study tested whether binge exposure limited to the latter half of
      this period (PD 7-9) produced selective spatial learning deficits that endured
      into adulthood. METHODS: On PD 7 to 9, Long-Evans rats were given intubations of
      alcohol (5.25 g/kg/day), sham intubations, or no intubations. Rats were tested as
      adults (>or=PD 70) in the Morris water maze under one of three different
      conditions: place (submerged escape platform in the same location each trial),
      random (submerged platform in a different, random location each trial), or
      redundant (visible platform that protruded above the water, in the same location
      for each trial). A 60-sec probe trial (with no platform present) followed the
      last acquisition trial. RESULTS: The mean peak blood alcohol concentration was
      401 mg/dl on PD 7. Neonatal alcohol treatment significantly impaired acquisition
      and reduced place biases on the probe trial in place-trained males, but not
      females. Neonatal alcohol treatment had no significant effects on acquisition
      performance of the random or redundant groups. Redundant training yielded rapid
      acquisition for all groups. The visible cue overshadowed place cues for all
      treatment groups, but small place biases were evident in controls. After random
      training, no group showed place biases. CONCLUSIONS: Heavy alcohol exposure in
      rats limited to the last half of the neonatal brain growth spurt caused enduring
      deficits in spatial learning, but only in males. The deficits were specific to
      place learning in the Morris water maze and emerged only when learning and
      performance depended on the use of distal place cues.

PMID- 11821659
TI  - Adduction of soluble proteins with malondialdehyde-acetaldehyde (MAA) induces
      antibody production and enhances T-cell proliferation.
AB  - BACKGROUND: The alcohol metabolites malondialdehyde and acetaldehyde can combine
      to form stable adducts (MAA) which are found in the livers of humans and rats
      after significant alcohol ingestion. While adducted proteins induce antibody
      responses in the absence of adjuvants, the mechanisms by which these responses
      occur are unknown. Thus, it was the purpose of these studies to investigate how
      MAA modification stimulates antibody and T-cell responses in the absence of
      adjuvants. METHODS: Hen egg lysozyme (HEL) was modified with increasing levels of
      MAA and was used as an immunogen, and antibody and T-cell responses were
      determined. The role of scavenger receptors in the immunogenicity of MAA-adducted
      proteins was also investigated. RESULTS: Maximum antibody response was induced
      after immunization with 1.8 nM MAA/nM HEL, and was primarily an IgG1 response to
      HEL as determined by inhibition ELISAs. T-cell proliferative responses after
      immunization with HEL-MAA were solely to HEL. Immunization with a scavenger
      receptor ligand in conjunction with HEL-MAA increased the predominant IgG1
      response and sharply decreased the IgG2a response by approximately 50%. Binding
      of HEL-MAA by splenocytes was determined by flow cytometry to be approximately
      15% greater than HEL alone, showing a doubling of the geometric mean
      fluorescence. Also, most of the cells that bound HEL-MAA were class II positive,
      indicating that antigen-presenting cells can bind the MAA-adducted HEL, and
      potentially initiate immune responses. CONCLUSIONS: MAA modification of proteins
      induces antibody and T-cell proliferative responses in vivo. Initial studies
      suggest that these responses may be mediated by scavenger receptors that
      recognize MAA-adducted proteins. This suggests a mechanism by which proteins
      modified with oxidative products associated with chronic ethanol consumption may
      alter immune responses that may play an active role in the development and/or
      progression of alcoholic liver disease.

PMID- 11821660
TI  - Chronic effects of prepubertal ethanol administration on steroidogenic acute
      regulatory protein in the rat ovary.
AB  - BACKGROUND: A mitochondrial protein, steroidogenic acute regulatory protein
      (StAR), plays an essential role in steroidogenesis by facilitating delivery of
      cholesterol across the mitochondrial membrane. Because ethanol (EtOH) causes
      suppressed estradiol (E2) secretion in prepubertal female rats and rhesus
      monkeys, we evaluated the effects of chronic EtOH administration on prepubertal
      ovarian StAR. METHODS: Rats were implanted with a gastric cannula on day 24 and
      began receiving control or EtOH diets on day 28. At 0800 hr on day 33, the
      experimental groups were subdivided. Half of the EtOH-treated animals received a
      subcutaneous injection of pregnant mare serum gonadotropin (PMSG; 15 IU), and the
      other half received an injection of saline. The chow-fed and liquid-diet control
      groups were also subdivided, with half receiving the PMSG and the other half
      receiving saline. Eight hours after the respective injections, the animals were
      killed, and their ovaries and blood were collected. RESULTS: The ovaries from
      EtOH-treated rats showed decreased basal expression of both the 3.8-kb (p < 0.05)
      and 1.7-kb (p < 0.01) StAR transcripts. PMSG-stimulated animals not exposed to
      EtOH showed a more than 2-fold increase (p < 0.01) in the ovarian levels of both
      transcripts. Western blot analysis revealed that EtOH exposure decreased (p <
      0.001) the basal expression of StAR protein, which paralleled the decrease in
      basal StAR messenger RNA. PMSG induced an increase (p < 0.001) in the levels of
      StAR protein, and this effect was blunted (p < 0.01) by EtOH. These changes
      observed in ovarian StAR protein were paralleled by decreases in serum
      pregnenolone and E2. CONCLUSIONS: These results demonstrate for the first time
      that ovarian StAR is a target for the chronic action of EtOH to alter prepubertal
      steroidogenesis, resulting in suppressed serum E2 secretion during a critical
      time of development.

PMID- 11821661
TI  - Involvement of acetaldehyde in alcohol addiction.
AB  - This article presents the proceedings of a symposium at the 2001 RSA Meeting in
      Montreal, Canada. The organizers and chairs were William J. McBride and Ting-Kai
      Li. The presentations were (1) Metabolism of ethanol in the brain and the
      behavioral consequences, by Richard A. Deitrich and Sergey Zimatkin; (2) Catalase
      production of acetaldehyde as a possible mediator of the psychopharmacological
      effects of ethanol, by Brian R. Smith; (3) The reinforcing actions of
      acetaldehyde in the ventral tegmental area, by Zachary A. Rodd-Henricks; and (4)
      Salsolinol and alcohol addiction, by William J. McBride.

PMID- 11821662
TI  - Molecular pathology and clinical aspects of alcohol-induced tissue injury.
AB  - Proceedings of a symposium at the 2001 RSA Meeting in Montreal, Canada; organized
      and co-chaired by Patricia E. Molina and Manuela Neuman. The presentations were
      (1) Mechanisms of alcohol-induced cell injury by Craig McClain; (2) Cytokines in
      alcoholic steatohepatitis and non-alcoholic steatohepatitis by Manuela Neuman;
      (3) Combination of alcohol and hepatitis C virus and liver injury by Dominique
      Valla; (4) Chronic ethanol exposure potentiates lipopolysaccharide liver injury,
      despite inhibiting Jun N-Terminal kinase and caspase 3 activation by Anna Mae
      Diehl; (5) Glutathione homeostasis in alcoholism: Role in alveolar epithelial
      barrier and lung injury by David M. Guidot; (6) Metabolic and inflammatory
      contribution of alcohol to trauma-induced tissue injury by Patricia E. Molina;
      (7) Growth factor and protein synthesis dysregulation: Role in alcoholic myopathy
      by Charles H. Lang.

PMID- 11821663
TI  - Implicit and explicit alcohol-related cognitions.
AB  - This article presents the proceedings of a symposium at the 2001 RSA Meeting in
      Montreal, Canada organized by Reinout W. Wiers and Alan W. Stacy. The purpose of
      the symposium was to present recent applications of implicit cognitive processing
      theory to alcohol research. Basic cognitive research has demonstrated that
      implicit cognition influences memory and behavior without explicit recall or
      introspection. The presentations from this symposium show that implicit cognition
      approaches yield new insights into understanding drinking motivation. The
      presentations were: (1) An introduction by Alan W. Stacy; (2) Implicit cognition
      and alcohol use. Involvement of other variables? (Susan L. Ames); (3) Alcohol
      expectancies and the art of implicit priming (Jane A. Noll); (4) Parental
      alcoholism and the effects of alcohol on semantic priming (Michael A. Sayette);
      (5) Implicit arousal and explicit liking of alcohol in heavy drinkers (Reinout W.
      Wiers); and (6) Negative affective cues and associative cognition in problem
      drinkers (Martin Zack). Comments were provided by the discussant Marvin Krank.
      The presented studies demonstrated that: (1) implicit memories of alcohol
      associations are powerful predictors and cross-sectional correlates of alcohol
      use; (2) implicit retrieval processes influence alcohol outcome expectancies and
      alcohol consumption; (3) alcohol consumption influences implicit memory
      processing; (4) heavy drinkers reveal different affective responses in implicit
      and explicit tasks; and (5) negative affect exerts an implicit priming effect for
      alcohol associations in problem drinkers. These findings illustrate the
      importance of implicit cognition in understanding alcohol abuse and demonstrate
      the potential of the theoretical framework for more widespread application across
      a variety of areas of alcohol research, including diagnostics for the risk of
      alcohol abuse, treatment, and prevention.

PMID- 11821665
TI  - Satisfaction with medical rehabilitation in patients with cerebrovascular
      impairment.
AB  - OBJECTIVE: Overall satisfaction has important social and economic implications
      for patients who have received inpatient medical rehabilitation. We conducted
      this study to examine the overall satisfaction level at 3- to 6-mo follow-up for
      inpatients with cerebrovascular impairments discharged from medical
      rehabilitation. DESIGN: The study was retrospective using information from a
      national database representative of medical rehabilitation patients across the
      United States. Information submitted in 1997 and 1998 to the Uniform Data System
      for Medical Rehabilitation by 177 hospital and rehabilitation facilities from 40
      states was examined. The final sample included 8,900 patient records. The main
      outcome measure was the level of satisfaction with medical rehabilitation at 80
      180 days postdischarge follow-up. RESULTS: A logistic regression model including
      ten independent variables was used to predict satisfied vs. dissatisfied at
      follow-up. Three statistically significant variables were included in the final
      model and correctly classified 95.1% of the patients. Higher FIM instrument
      discharge scores were associated with increased satisfaction. Further analysis of
      the FIM instrument subscales indicated that higher ratings in transfers, social
      cognition, and locomotion were significantly associated with increased
      satisfaction. CONCLUSION: We identified several functional variables associated
      with increased satisfaction after medical rehabilitation in persons with stroke.
      The ability to objectively assess patient satisfaction is important as consumer
      based outcome measures are integrated in accreditation and healthcare evaluation.

PMID- 11821666
TI  - Pudendal nerve conduction to evaluate organic erectile dysfunction.
AB  - OBJECTIVE: This study aimed to evaluate the value of testing pudendal nerve
      conduction in men with erectile dysfunction. DESIGN: This open prospective study
      was conducted on 150 men with documented erectile dysfunction of at least 6 mo of
      duration, all of whom underwent pudendal nerve conduction by the same
      investigator. RESULTS: Only patients with erectile dysfunction and low back pain
      (n = 9) showed statistically significant prolonged pathologic pudendal nerve
      conduction latency of 43.1 msec/div (SD +/- 11.3 msec/div, P < 0.05). There were
      no correlations between the pudendal nerve conduction latency in patients
      suffering from erectile dysfunction associated with diabetes mellitus, local
      trauma, pelvic surgery, or antihypertensive drugs. CONCLUSIONS: Pudendal nerve
      conduction may contribute valuable information to the evaluation of patients with
      erectile dysfunction caused by neurologic deficits as manifested by low back
      pain.

PMID- 11821667
TI  - Dalteparin vs. enoxaparin as prophylaxis for deep-vein thrombosis after total hip
      or knee arthroplasty: a retrospective analysis.
AB  - OBJECTIVE: To assess the clinical and economic consequences of a formulary switch
      from enoxaparin to dalteparin as first-line prophylaxis for deep-vein thrombosis
      in patients undergoing inpatient rehabilitation after total hip arthroplasty or
      total knee arthroplasty. DESIGN: Retrospective cohort study. RESULTS: There were
      461 patients eligible for the study. The age-adjusted risk of a deep-vein
      thrombosis event confirmed by duplex ultrasonography among patients treated with
      dalteparin was substantially lower than among patients treated with enoxaparin,
      whereas the age-adjusted risk of a bleeding event in the dalteparin group was
      also lower than that in the enoxaparin group. Adjusted per capita costs of deep
      vein thrombosis prophylaxis during the rehabilitation stay were $129 lower among
      subjects treated with dalteparin. CONCLUSION: The switch to dalteparin as a first
      line therapy for deep-vein thrombosis prophylaxis in the rehabilitation period
      after total hip arthroplasty or total knee arthroplasty has led to substantial
      cost savings for Kessler Institute without compromising patient care.

PMID- 11821669
TI  - A patient-oriented health status measure in outpatient rehabilitation.
AB  - OBJECTIVES: The purpose of this study was to assess the utility of a patient
      centered health status measurement tool in multiple outpatient rehabilitation
      clinics and to characterize health status before and after an outpatient physical
      therapy intervention as part of that assessment. DESIGN: Six outpatient
      rehabilitation clinics voluntarily agreed to incorporate a standardized patient
      centered health status questionnaire into everyday practice. Patients completed
      the SF-36 health status questionnaire before initiating treatment and again at
      discharge. Only nonsurgical patients without comorbidities were enrolled.
      RESULTS: Voluntary application of the SF-36 on a small scale was achieved over a
      period of 3-4 mo. All health concepts improved except general health perceptions.
      CONCLUSION: The results suggest that (1) a standard patient-oriented health
      status questionnaire can be incorporated into outpatient rehabilitation clinics,
      and useful information can be derived regarding outcomes; (2) careful
      administrative coordination is necessary to optimize follow-up and decrease
      burden on both patients and clinicians; (3) although improvements in health
      status were demonstrated, small sample sizes and the lack of control groups
      prevents conclusions regarding the effectiveness of physical therapy treatment;
      and (4) the magnitude of effect sizes suggests that controlled studies could be
      performed by clinicians partnering with researchers to improve outpatient
      rehabilitation.

PMID- 11821671
TI  - Postural sway during cane use by patients with stroke.
AB  - OBJECTIVE: To quantitatively evaluate the effects of body support with a cane on
      postural sway by measuring gravity-center sway of patients with stroke who reside
      at home. DESIGN: The subjects were 41 patients with stroke and 36 healthy
      independent elderly people. Each subject stood in the standard Romberg position
      on a gravicorder under two conditions: without support and with a cane. RESULTS:
      In both groups, the largest area of gravity-center sway occurred when the
      subjects stood without support. The area of gravity-center sway of the patients
      with stroke was significantly greater than that of the healthy independent
      elderly. In the patients with stroke group, the percentage decrease in the
      standing position with the cane was 58.0% in the men and 53.9% in the women, as
      opposed to 67.7% in the men and 67.8% in the women in the group of healthy
      independent elderly. CONCLUSION: The authors quantitatively evaluated the effects
      of body support with a cane on postural sway of patients with stroke. The effect
      of body support with cane on postural sway of patients with stroke was more
      effective than that of healthy independent elderly.

PMID- 11821673
TI  - Successes and setbacks of the falls consultation: report on the first 150
      patients.
AB  - OBJECTIVE: We report the results of a Falls Consultation. DESIGN: Data concerning
      the first 150 patients are reported. Each patient was assessed by a geriatrician,
      a neurologist, and a physiatrist, who visited him or her at home, and was
      reassessed by the same geriatrician 6 mo later. RESULTS: Of the 150 patients, 135
      patients completed the initial evaluation. Most of them were frequent fallers.
      The population was very heterogeneous regarding the health status and the degree
      of disability. In most cases, falls were the result of several interacting
      factors. The most frequent recommendations from the staff were physical therapy,
      environmental changes, and medication changes. Over the following 6 mo,
      approximately one out of four patients had experienced new falls. However, the
      risk of falling was significantly reduced (5.3 +/- 7.3 falls in 6 mo before vs.
      0.8 +/- 1.6 falls in 6 mo after the intervention). The Activities of Daily Living
      score was a predictor of recurrent falls, hospitalization, and
      institutionalization. CONCLUSION: Our results show that a multidisciplinary falls
      consultation can be efficient in reducing the risk of falls in nonselected
      elderly fallers but suggest that differential strategies are needed to manage
      adequately the more vigorous and the frail old person as well.

PMID- 11821676
TI  - Federal agency management practices for prioritizing and funding rehabilitation
      related research.
AB  - This article focuses on the processes by which priorities are established and
      research is funded by three organizational entities that finance the
      preponderance of this country's rehabilitation-related research: the National
      Institute on Disability and Rehabilitation Research, the National Center for
      Medical Rehabilitation Research (the focal point of rehabilitation research at
      the National Institutes of Health), and the National Institutes of Health in
      aggregate (i.e., the several institutes that support rehabilitation-related
      research). Two perspectives are emphasized: the stakeholders' opportunities to
      influence deliberations at key steps in setting priorities and reaching funding
      decisions and the extent to which these management practices are explicitly
      conceptualized, transparent, and evidence-based. Those perspectives are brought
      to bear on three pivotal considerations: the agencies' commitment to directed vs.
      nondirected research, the role they assign to strategic planning, and their
      approach to reviewing applications for funding.

PMID- 11821674
TI  - Bladder management and quality of life after spinal cord injury.
AB  - OBJECTIVE: This study examines the quality of life among individuals with spinal
      cord injury requiring assistance for bowel and bladder management vs. those with
      independent control of bowel and bladder. DESIGN: Two groups of 53 individuals
      each were matched case for case on age, education, sex, race, and lesion level.
      Outcome measures included the Satisfaction With Life Scale, the Craig Handicap
      Assessment and Reporting Technique (CHART), and the SF-12. RESULTS: Satisfaction
      with life was significantly lower among dependent individuals with impaired bowel
      and bladder functioning as compared with individuals with independent bowel and
      bladder control. Similarly, dependent individuals reported greater self-reported
      handicap (CHART) than independent individuals in the areas of physical
      independence, mobility, and occupational functioning. However, dependent and
      independent individuals did not differ in the areas of social integration and
      economic self-sufficiency. Item analysis on the CHART item assessing number of
      social contacts initiated in the previous month suggested that dependent
      individuals may have difficulty initiating new social contacts. Independent
      individuals reported better overall physical health (SF-12) than dependent
      individuals. Mental health (SF-12), however, did not differ across groups.
      CONCLUSIONS: Individuals with impaired bowel and bladder control reported lower
      quality of life on several domains compared with those with independent control
      of bowel and bladder. Though the two groups did not differ in self-reported
      social integration, dependent individuals may have greater difficulty creating
      new social relationships.

PMID- 11821677
TI  - Intramuscular electromyographically controlled neuromuscular electrical
      stimulation for upper limb recovery in chronic hemiplegia.
AB  - We report three cases of survivors of chronic stroke who were treated with active
      repetitive movement training of the paretic finger extensors mediated by
      intramuscular electromyographically controlled neuromuscular electrical
      stimulation for the purpose of motor relearning. These case reports demonstrate
      the feasibility of using intramuscular electromyographically controlled
      neuromuscular electrical stimulation for facilitating the upper limb motor
      recovery of chronic stroke survivors with mild to moderate hemiplegia.

PMID- 11821678
TI  - Rehabilitation and fear: what happens if the house catches on fire?

PMID- 11821681
TI  - Trabeculectomy--not only filtration.

PMID- 11821679
TI  - From who's who to who's he? A quality of life survey for retired physiatrists and
      spouses.

PMID- 11821682
TI  - Factors leading to reduced intraocular pressure after combined trabeculotomy and
      cataract surgery.
AB  - PURPOSE: To determine the factors that control intraocular pressure (IOP) after
      trabeculotomy combined with phacoemulsification and intraocular lens implantation
      as an initial procedure in adults with primary open-angle glaucoma (POAG).
      METHODS: A consecutive series of 141 eyes with POAG or ocular hypertension was
      prospectively recruited. One hundred five eyes were treated by combined
      trabeculotomy and cataract surgery (TPI group) and 36 eyes were treated by
      cataract surgery alone (PI group). The prognostic factors that correlate with
      successful IOP control after surgery were screened using the Cox multivariate
      analyses based on three definitions of success: IOP <21 mm Hg, <17 mm Hg, and <15
      mm Hg, with or without eye drops. The factors examined were types of procedure
      (TPI or PI), age, sex, preoperative IOP level, number of preoperative
      antiglaucoma medications, eyes with high myopia (>-10 diopters), postoperative
      hyphema lasting longer than 4 days, and postoperative transient IOP spike (>30 mm
      Hg). RESULTS: TPI was a significant factor for IOP reduction in the three
      definition-based multivariate analyses. Other factors included patient age,
      preoperative IOP level, and postoperative IOP spike. The statistical significance
      of age was further confirmed using linear regression analysis and the Spearman
      correlation coefficient (Rs) between age and IOP level 3 months after surgery
      (R(2)=0.13, P = 0.0002 and Rs=-0.44, P < 0.0001, respectively in the TPI group).
      The success rates for IOP control <17 mm Hg and <15 mm Hg were significantly
      higher in patients 70 years and older than in younger patients, as determined
      using the Kaplan-Meier life table analysis with the Mantel-Cox logrank test in
      both TPI and PI groups. IOP reduction was significantly greater in older patients
      than in younger patients at every follow-up visit for up to 1.5 years for the TPI
      group and up to 1 year for the PI group. CONCLUSION: Advanced age is a favorable
      prognostic factor for successful control of IOP after combined trabeculotomy and
      cataract surgery. Older patients with POAG and visually significant cataract are
      good candidates for combined trabeculotomy and cataract surgery.

PMID- 11821684
TI  - Activity of dissolved mitomycin C after different methods of long-term storage.
AB  - PURPOSE: The cytostatic substance mitomycin C (MMC) is used in trabeculectomy to
      enhance the success rate in problematic cases and is usually dissolved
      immediately before application, but only approximately 1% of the substance is
      needed for treatment. The authors evaluated different methods of long-time
      storage of MMC for a period of 6 months. METHODS: MMC in concentrations of 0.02,
      0.05, 0.1, 0.2, and 0.4 mg/mL was prepared at the local pharmaceutical department
      and stored at +22 degrees C (room temperature), +4 degrees C (refrigerator), -20
      degrees C (freezer compartment), and -196 degrees C (liquid N2). The activity of
      MMC was evaluated with a microagar diffusion method (bioassay) after 30 minutes,
      and 1, 3, 7, 14, 30, 90, and 180 days for the different concentrations and
      storage methods. RESULTS: There was no difference in the long-term stability of
      the investigated MMC concentrations. Ninety percent of the initial activity was
      preserved after storage at +22 degrees C for 1 week, -20 degrees C for 1 month,
      or +4 degrees C for 3 months. At 6 months the activities were 16%, 48%, and 78%
      of the initial values, respectively. The activity of MMC stored at -196 degrees C
      is not reduced after storage for 6 months. CONCLUSIONS: Dissolved MMC can be
      stored in the refrigerator for up to 3 months without significant loss of
      activity. Storage at room temperature is not recommended. Costs of trabeculectomy
      can be reduced by storage of reconstituted solutions rather than dissolving MMC
      before each glaucoma surgery.

PMID- 11821683
TI  - Free conjunctival autologous graft for bleb repair and bleb reduction after
      trabeculectomy and nonpenetrating filtering surgery.
AB  - PURPOSE: To describe methods and outcomes of excisional revision of a filtering
      bleb (bleb revision) using free conjunctival autologous graft either for bleb
      repair or for bleb reduction after trabeculectomy and deep sclerectomy with an
      implant. METHODS: Retrospective medical records were reviewed for a consecutive
      non-comparative case series comprising patients who underwent excisional revision
      of a filtering bleb between May 1998-January 2001. Excisional revision using free
      conjunctival autologous graft (bleb revision) was performed either for bleb
      repair, to treat early and late leaks and hypotony with maculopathy, or for bleb
      reduction, to improve ocular pain, discomfort, burning, foreign body sensation,
      tearing, and fluctuations of visual acuity. The revision consisted of bleb
      excision and free conjunctival autologous graft. The bleb histopathology was
      analyzed in patients who underwent bleb repair. RESULTS: Sixteen patients were
      included in the study, consisting of nine patients who had a trabeculectomy and
      seven patients who had a deep sclerectomy with an implant. Bleb revision was
      necessary in 14 patients due to leaking filtering bleb (bleb repair), and in 2
      patients due to bleb dysesthesia (bleb reduction). After a follow-up of 15.1 +/-
      8.4 months, the mean intraocular pressure (IOP) rose from 7.8 +/- 6.3 mm Hg to
      14.3 +/- 6.5 mm Hg, and the visual acuity from 0.4 +/- 0.3 to 0.7 +/- 0.3, with a
      P value of 0.008 and 0.03, respectively. The complete success rate at 32 months,
      according to the Kaplan-Meier survival curve, was 38.3%, and the qualified
      success rate was 83.3%. Four patients (25%) required additional suturing for
      persistent bleb leak. To control IOP, antiglaucoma medical therapy was needed for
      six patients (37.5%) and repeated glaucoma surgery was needed for one patient.
      CONCLUSION: Free conjunctival autologous graft is a safe and successful procedure
      for bleb repair and bleb reduction. However, patients should be aware of the
      postoperative possibility of requiring medical or surgical intervention for IOP
      control after revision.

PMID- 11821685
TI  - Physical effects of reuse and repeated ethylene oxide sterilization on
      transscleral cyclophotocoagulation laser G-probes.
AB  - PURPOSE: The authors documented the physical effects of reuse and repeated
      ethylene oxide sterilization on transscleral cyclophotocoagulation laser G
      probes. METHODS: Transscleral cyclophotocoagulation was performed using G-probes
      on fresh porcine eyes. Each of two G-probes was used for four transscleral
      cyclophotocoagulation procedures, with three cycles of ethylene oxide
      sterilization in between. The power output from the G-probes was measured by a
      laser output meter before and after each transscleral cyclophotocoagulation
      procedure. The G-probes were also examined under a slit lamp for signs of
      physical damage. RESULTS: Repeated use of the G-probe in transscleral
      cyclophotocoagulation, with ethylene oxide sterilization in between, resulted in
      an average decrease of 3% in laser energy delivered per repeated cycle of use up
      to the fourth cycle. No signs of physical damage were found. CONCLUSIONS: Laser G
      probes remain functional after repeated use and ethylene oxide resterilization
      for up to four cycles. No visible physical damage to the probes was identified.
      It is safe and cost-effective to reuse G-probe for transscleral
      cyclophotocoagulation with ethylene oxide sterilization, provided the surgeon
      stays alert for signs of probe damage. This alertness should be retained
      regardless of whether new or old G-probes are used.

PMID- 11821686
TI  - Retrobulbar catheter technique for postoperative titratable analgesia after
      glaucoma surgery.
AB  - PURPOSE: To assess an indwelling retrobulbar catheter for delivery of
      intraoperative anesthesia and postoperative analgesia in patients undergoing
      painful cyclodestructive and retinal destructive procedures as treatment of
      neovascular glaucoma. PATIENTS AND METHODS: The prospective clinical
      interventional study included all 11 patients undergoing cyclocryocoagulation
      and/or retinal exocryocoagulation as treatment of neovascular glaucoma due to
      proliferate ischemic retinopathies. Using a commercially available retrobulbar
      needle with a diameter of 0.80 mm and a length of 38 mm, 7 mL of a local
      anesthetic were injected. Through the same needle, a 28-gauge commercially
      available flexible catheter was introduced into the retrobulbar space, the needle
      was withdrawn, and the catheter was fixed in place. When the patients began to
      feel pain during or after surgery, 2 mL of a local anesthetic were reinjected
      through the catheter. The catheter was removed 24 hours after surgery. RESULTS:
      Due to increasing pain in the postoperative period, 8 (72.7%) patients received a
      reinjection 156.3 +/- 94.6 minutes after the preoperative injection. Seven
      (63.6%) patients requested a second reinjection 268.6 +/- 45.7 minutes after the
      preoperative injection, and three (27.3%) patients requested a third
      postoperative injection 333.3 +/- 79.1 minutes after the preoperative injection.
      Reinjection of the local anesthetic through the catheter markedly decreased the
      pain within 5 minutes of injection in all patients. CONCLUSIONS: Avoiding side
      effects of systemic analgesics and sedatives, an indwelling retrobulbar catheter
      for repeat postoperative injections of local anesthetics is useful and effective
      for titratable postoperative analgesia after painful cyclodestructive or retinal
      destructive surgery as treatment of neovascular glaucoma.

PMID- 11821687
TI  - Quantification of interpoint topographic correlations of threshold values in
      glaucomatous visual fields.
AB  - PURPOSE: The authors sought to quantify neighboring and distant interpoint
      correlations of threshold values within the visual field in patients with
      glaucoma. METHODS: Visual fields of patients with confirmed or suspected glaucoma
      were analyzed (n = 255). One eye per patient was included. Patients were examined
      using the 32 program of the Octopus 1-2-3. Linear regression analysis among each
      of the locations and the rest of the points of the visual field was performed,
      and the correlation coefficient was calculated. The degree of correlation was
      categorized as high (r(2) > 0.66), moderate (0.66 > or = r(2) > 0.33), or low
      (r(2) < or = 0.33). The standard error of threshold estimation was calculated.
      RESULTS: Most locations of the visual field had high and moderate correlations
      with neighboring points and with distant locations corresponding to the same
      nerve fiber bundle. Locations of the visual field had low correlations with those
      of the opposite hemifield, with the exception of locations temporal to the blind
      spot. The standard error of threshold estimation increased from 0.6 to 0.9 dB
      with an r(2) reduction of 0.1. CONCLUSION: Locations of the visual field have
      highest interpoint correlation with neighboring points and with distant points in
      areas corresponding to the distribution of the retinal nerve fiber layer. The
      quantification of interpoint correlations may be useful in the design and
      interpretation of visual field tests in patients with glaucoma.

PMID- 11821688
TI  - Sensitivity differences between real-patient and computer-stimulated visual
      fields.
AB  - PURPOSE: The authors sought to verify computer simulation of visual fields by
      comparing thresholds of real and corresponding simulated visual fields. METHODS:
      Four patients with stable glaucomatous visual fields and three patients with
      progressing glaucomatous visual fields were chosen for the study. Visual fields
      had been recorded at 6-month intervals for 5 to 7.5 years. A previously described
      computer simulation program was used to generate a corresponding simulated visual
      field for each of the real fields. Twenty different levels of response
      variability and long-term variability were used in the simulations. Pointwise
      sensitivity differences between real and simulated fields were calculated. The
      average difference and 95% interval of the differences were analyzed for the
      different simulation conditions, for the pointwise sensitivities in the real
      patient fields, and to determine whether the field was stable or progressing.
      RESULTS: In almost all simulation conditions, the average pointwise sensitivity
      differences ranged from -1 to 1 dB and were not significantly different among
      different simulation conditions. The 95% interval of the average difference
      increased significantly with response variability, whereas long-term variability
      failed to show any apparent effect. Average pointwise differences and the 95%
      intervals were greatest in locations where the real-patient field had reduced
      sensitivity of 14 dB or worse. CONCLUSION: The simulation program provided good
      estimates of visual field sensitivities. Increasing amounts of response, but not
      long-term variability, produced a linear increase in the variability of threshold
      sensitivities. This finding implies that short-term rather than long-term
      fluctuation is the most important factor determining the variability of
      thresholds.

PMID- 11821689
TI  - Frequency doubling perimetry in glaucoma.
AB  - PURPOSE: To evaluate the validity of frequency doubling perimetry (FDP) in the
      detection of glaucomatous field defects. METHODS: Group I consisted of 85 eyes of
      85 patients with established field defects in automated perimetry, classified by
      severity of defect. Group II consisted of 48 eyes of 48 control subjects. Both
      groups underwent Swedish Interactive Testing Algorithm (SITA) standard tests as
      well as FDP screening strategies (C20-1 and C20-5 and full threshold test).
      Sensitivity and specificity measures for the FDP tests were calculated using one
      new and two previously published algorithms. RESULTS: A described scoring system
      provided the best sensitivity (85.9%) and specificity (95.1%). For moderate and
      severe cases, the sensitivity improved to 91%. Quantification of the defect did
      not improve detection. CONCLUSIONS: FDP is a valid screening test for glaucoma.
      The scoring system described by Patel et al. provided the best results.

PMID- 11821690
TI  - Genetic analysis of PITX2 and FOXC1 in Rieger Syndrome patients from Brazil.
AB  - PURPOSE: Axenfeld-Rieger syndrome is a genetically heterogeneous, autosomal
      dominant disorder that is characterized by anterior segment defects, glaucoma,
      and extraocular anomalies. This study examined the two genes known to cause
      Rieger syndrome, PITX2 and FOXC1, for mutations in five Brazilian families with
      Axenfeld-Rieger syndrome. METHODS: Five families with a total of 23 persons
      affected by Axenfeld-Rieger syndrome were recruited for this study. A sequencing
      based mutation screen was undertaken for the PITX2 and FOXC1 genes. Linkage
      analysis was used to study one large family for which no mutations were detected
      in the PITX2 or FOXC1 genes. RESULTS: Two of the five families harbored mutations
      in the PITX2 gene, but none of the families had a detectable FOXC1 mutation.
      Haplotypic analysis of three Rieger syndrome regions in a large family with
      Axenfeld-Rieger syndrome excluded linkage to the 4q25 (PITX2), 6p25 (FOXC1), and
      13q14 (RIEG2) regions. CONCLUSIONS: It appears that the PITX2 gene is responsible
      for a significant portion of Axenfeld-Rieger syndrome in the Brazilian
      population. Furthermore, there is also evidence for the presence of genetic
      heterogeneity of the disorder within the Brazilian population. Finally, a large
      family with Axenfeld-Rieger syndrome has been identified that does not appear to
      harbor any of the three known loci. Axenfeld-Rieger syndrome gene segregation in
      this family likely represents a novel locus.

PMID- 11821692
TI  - Effectiveness of nonocclusive ligature and fenestration used in Baerveldt aqueous
      shunts for early postoperative intraocular pressure control.
AB  - PURPOSE: The authors determined the effectiveness of two different methods of
      modification of Baerveldt aqueous shunts in the control of early postoperative
      intraocular pressure. METHODS: The authors retrospectively reviewed charts of 122
      eyes of 113 patients who underwent a Baerveldt 350-mm(2) modified with tube
      fenestration and charts of 129 eyes of 122 patients who underwent a Baerveldt 350
      mm(2) modified with a nonocclusive ligature to examine early postoperative
      intraocular pressure control. In the fenestration group, the tube was modified
      with a 4-0 intraluminal suture and an occlusive 6-0 external polyglactin ligature
      before ocular placement. After ocular placement, the tube was further modified
      with one to three perforating fenestrations. In the nonocclusive-ligature group,
      the tube was modified with a 4-0 nylon intraluminal suture with a nonocclusive 6
      0 external polyglactin ligature before ocular placement. RESULTS: A total of 94
      eyes (77%) achieved adequate intraocular pressure control with or without
      adjunctive medications and. A total of 28 eyes (23%) had postoperative
      hypertension or hypotony in the fenestration group versus 81 (62.8%) and 48
      (37.2%) eyes in the nonocclusive-ligature group (P = 0.014), respectively. The
      mean change in intraocular pressure preoperatively and 3 months postoperatively
      was 18.2 mm Hg versus 21.0 mm Hg (P = 0.11) in the fenestration and nonocclusive
      ligature groups, respectively. CONCLUSIONS: Both the nonocclusive ligature and
      the fenestration methods provide desirable decreases in intraocular pressure in
      the immediate postoperative period and 3 months postoperatively; however, the
      fenestration modification may achieve adequate intraocular pressure control more
      often in the early postoperative period.

PMID- 11821691
TI  - Effects of isopropyl unoprostone and latanoprost on melanogenesis in mouse
      epidermal melanocytes.
AB  - PURPOSE: The authors sought to investigate the cellular mechanism of
      melanogenesis by prostaglandin antiglaucomatous compounds, isopropyl unoprostone
      (referred to as unoprostone) and latanoprost, and to quantitatively compare their
      effect on melanogenesis using cultured mouse epidermal melanocytes. METHODS: M1,
      M2, and the acid of latanoprost, all of which are possible intraocular
      metabolites of unoprostone or latanoprost, were used. Tested prostaglandin
      related compounds (final concentration range, 1 micromol/L-10 nmol/L) were
      administrated to the culture medium of purely cultured mouse melanoblasts, melan
      A, once daily for 2 weeks. One micromole per liter prostaglandin F(2 alpha)
      solution was administered in parallel. Radioisotope assays were used to measure
      the total melanin synthesis and the activity of tyrosinase in converting tyrosine
      to L-3,4-dihydroxyphenylalanine, which is a rate-limiting reaction in
      melanogenesis. The effects of prostaglandin F(2 alpha), M1, or M2 on
      proliferation of melan-A were examined. RESULTS: M1, M2, and acid of latanoprost
      but not prostaglandin F(2 alpha), significantly enhanced tyrosinase activity. M2
      and acid of latanoprost more greatly enhanced tyrosinase activity than did M1.
      None of the tested compounds significantly altered the proliferation and total
      melanin synthesis of melan-A. CONCLUSIONS: Both unoprostone and latanoprost
      enhanced tyrosinase activity. These prostaglandin-related compounds may influence
      the nature of melanin and result in pigmentation.

PMID- 11821693
TI  - Management of iris melanoma with secondary glaucoma.

PMID- 11821695
TI  - Re: Ajayi OB, Ukwade NT. Caffeine and intraocular pressure in Nigerian
      population. J Glaucoma 2001;10:25-31.

PMID- 11821696
TI  - Intima-media thickness: a new tool for diagnosis and treatment of cardiovascular
      risk.
AB  - Increased intima-media thickness (IMT) is a non-invasive marker of early arterial
      wall alteration, which is easily assessed in the carotid artery by B-mode
      ultrasound, and more and more widely used in clinical research. Methods of IMT
      measurement can be categorized by two approaches: (i) measurement at multiple
      extracranial carotid sites in near and far walls and (ii) computerized
      measurement restricted to the far wall of the distal common carotid artery.
      Because IMT reflects global cardiovascular risk, its normal value might be better
      defined in terms of increased risk rather than in terms of statistical
      distribution within a healthy population. The available epidemiological data
      indicate that increased IMT (at or above 1 mm) represents a risk of myocardial
      infarction and/or cerebrovascular disease. Close relationships have been shown
      between: (i) most traditional cardiovascular risk factors; (ii) certain emerging
      risk factors such as lipoproteins, psychosocial status, plasma viscosity, or
      hyperhomocysteinemia; and (iii) various cardiovascular or organ damages such as
      white matter lesion of the brain, left ventricular hypertrophy, microalbuminuria
      or decreased ankle to brachial systolic pressure index. Thus, IMT gives a
      comprehensive picture of the alterations caused by multiple risk factors over
      time on arterial walls. Prospective primary and secondary prevention studies have
      also shown that increased IMT is a powerful predictor of coronary and
      cerebrovascular complications (risk ratio from 2 to 6) with a higher predictive
      value when IMT is measured at multiple extracranial carotid sites than solely in
      the distal common carotid artery. Therapeutic double-blind trials have shown that
      lipid-lowering drugs, such as resin and overall statines, and to a lesser extent
      antihypertensive drugs, such as calcium antagonists, may have a beneficial effect
      on IMT progression in asymptomatic or in coronary patients. However,
      methodological standardization of IMT measurement still needs to be implemented
      before routine measurement of IMT can be proposed in clinical practice as a
      diagnostic tool for stratifying cardiovascular risk in primary prevention and for
      aggressive treatment decision. It can be anticipated however, that the presence
      of increased carotid IMT in one individual with intermediate cardiovascular risk
      would lead to his classification into the high-risk category and thus influence
      the aggressiveness of risk factor modifications.

PMID- 11821697
TI  - Independent effects of smoking on risk of hypertension: small, if present.

PMID- 11821698
TI  - Association studies in cardiovascular medicine.

PMID- 11821699
TI  - Autoregulation of blood flow, endothelial nitric oxide synthase and microvascular
      rarefaction.

PMID- 11821701
TI  - Antagonists of the angiotensin II type 1 receptor: an approach to control
      vascular disease beyond blood pressure lowering?

PMID- 11821700
TI  - Vascular smooth muscle growth and extracellular matrix deposition: is there a
      role for the sympathetic nervous system?

PMID- 11821702
TI  - The risk of hypertension in men: direct and indirect effects of chronic smoking.
AB  - OBJECTIVES: To assess the risk of hypertension associated with smoking status.
      DESIGN: A population-based cross-sectional study in 12 417 men screened for a
      routine medical and biological check-up provided by their medical insurance at
      the 'Institut inter-Regional pour la Sante' (IRSA, Regional Institute for
      Health), a group of 10 medical centres in Western and Central France. MAIN
      OUTCOME MEASURES: The prevalence and the relative risk of hypertension associated
      with smoking status. RESULTS: Overall, the prevalence of hypertension was higher
      in former smokers than in never smokers (13.5 versus 8.8%, P < 0.001). The risk
      of hypertension was higher [odds ratio (OR) 1.31 (1.13-1.52), P < 0.001] in
      former smokers than in never smokers, independently of age and alcohol intake.
      Both current and former smokers were at risk for systolic hypertension,
      especially those subjects aged 60 years and above. The risk of hypertension was
      associated with the number of cigarettes smoked [OR per 10 cigarettes smoked
      daily: 1.13 (1.05-1.21), P < 0.001] and the duration of smoking cessation [OR
      0.99 (0.98-1.00), P = 0.01]. When body mass index was entered into the model, the
      risk of hypertension in former smokers was no longer significant; however,
      current smokers remained at risk for systolic hypertension. CONCLUSIONS: Former
      smokers are at risk for hypertension, probably because of the higher prevalence
      of overweight and obese subjects in this group. Current smokers are also at risk
      for systolic hypertension, especially in those subjects aged 60 years or older.
      However, this risk is independent of body mass index.

PMID- 11821704
TI  - Increased sodium concentrations in drinking water increase blood pressure in
      neonates.
AB  - BACKGROUND: In a previous study, we found that increased sodium concentrations in
      the drinking water led to an increase in mean arterial pressure (MAP) and
      systolic blood pressure (SBP) in fourth- and fifth-grade school children. Milk
      powder formulae have a low content of sodium, almost identical to that of breast
      milk. However, the final sodium concentration in the milk formula depends upon
      the concentration of sodium in the diluting water, which varies remarkably.
      OBJECTIVE: To evaluate changes in blood pressure during the first 2 months of
      life in neonates receiving low-sodium mineral water (LSMW), high-sodium tap water
      (HSTW), or breast milk. DESIGN: A randomized, prospective study in a teaching
      hospital. METHODS: Fifty-eight Jewish term infants maintained on milk formula
      were randomly assigned to two groups. Group 1 consisted of 25 infants whose
      formula was diluted with LSMW (Eden Spring Mineral Water) having a sodium
      concentration of 32 mg/l (1.4 mmol/l). Group 2 contained 33 infants whose formula
      was diluted with HSTW having a sodium concentration of 196 mg/l (8.5 mmol/l).
      Fifteen breastfed babies served as the control group (group 3). Weekly weight,
      height, head circumference, heart rate, and systolic (SBP), diastolic (DBP) and
      mean (MAP) blood pressures were recorded for each infant for 8 consecutive weeks
      after birth. After 8 weeks, group 1 reverted to a diet similar to that of group
      2. At 6 months of age (week 24), a follow-up blood pressure measurement was
      performed in 11, 20 and seven infants in groups 1, 2 and 3, respectively. Blood
      pressure was measured during sleep. Urinary sodium : creatinine ratio was
      determined monthly during the initial 2 months. RESULTS: Increases in weight and
      height were equal in all groups. Heart rate did not differ between groups during
      the entire study period. From the age of 6 weeks until week 8, MAP, SBP and DBP
      were found to be significantly greater in the group 2 (HSTW). In parallel, the
      urinary sodium : creatinine ratio was significantly greater in this group. At
      week 24, blood pressure values in group 1 increased towards those of group 2.
      CONCLUSIONS: Diluting milk formula with tap water containing a high concentration
      of sodium will result in the infant being fed a high-salt diet. To equilibrate
      with breast milk, formula should be diluted with low-salt water. Blood pressure
      in the neonate is increased by a high sodium intake via drinking water.

PMID- 11821703
TI  - Tracking of systolic blood pressure during childhood: a 15-year follow-up
      population-based family study in eastern Finland.
AB  - OBJECTIVES: To investigate the tracking of systolic arterial blood pressure (SBP)
      during childhood. DESIGN AND SETTING: All children born during 1981-82 in a rural
      community of eastern Finland were followed at the ages of 6 months, 7 and 15
      years (SBP-6m, SBP-7y, SBP-15y). One hundred and thirty-eight out of 205 children
      completed the full follow-up period, of which 100 (45 girls) were included in the
      analysis with complete data. MAIN OUTCOME MEASURES: SBP (mmHg). RESULTS: SBP-6m
      was associated with SBP-7y (r = 0.715; P < 0.001) and with SBP-15y (r = 0.238; P
      = 0.017) and SBP-7y was associated with SBP-15y (r = 0.348; P < 0.001).
      Adjustment for confounders did not change these results. Children at the highest
      tertile of SBP-6m had a higher probability of being at the highest tertile of SBP
      7y [relative risk (RR) = 4.3; 95% confidence interval (CI), (2.4-7.6)] and SBP
      15y [RR = 1.9; 95% CI, (1.1-3.3)]. Children at the highest tertile of SBP-7y had
      a higher probability of being at the highest tertile of SBP-15y [RR = 2.6 (1.5
      4.6)]. The regression analysis showed a significant main effect on SBP-15y for
      birth weight (negative association), male gender, current body mass index (BMI),
      change of BMI between the ages of 7 years and 15 years, SBP-6m, SBP-7y and the
      mean SBP between the ages of 6 months and 7 years (all with positive
      association). Children with family history of hypertension appear to have a
      higher SBP during childhood; however, this association did not reach a
      significant level. CONCLUSIONS: The study confirmed the tracking of SBP during
      childhood. Birth weight was inversely associated with SBP-15y. Family history of
      hypertension was not significantly associated with SBP during childhood.

PMID- 11821705
TI  - Identification and chromosomal localization of ecogenetic components of
      electrolyte excretion.
AB  - OBJECTIVE: To determine to what extent urinary excretion of blood pressure
      modulating electrolytes is genetically determined, and to identify their
      chromosomal localization. DESIGN AND METHODS: Twenty-six rat recombinant inbred
      strains (RIS) originating from reciprocal crosses of normotensive Brown Norway
      (BN.Lx) and spontaneously hypertensive rats (SHR) were used. A pilot experiment
      on a subset of strains determined that fasting decreases the impact of
      environmental noise and increases that of heritability. Twenty-four-hour urinary
      collections were obtained from fasting rats aged 6-12 weeks (3-8 rats per
      strain). Sodium (Na), potassium (K) and calcium (Ca) excretions were measured,
      and the Na/K ratio calculated. These phenotypes served as quantitative traits for
      the search of quantitative trait loci (QTLs) by scanning the RIS genome that was
      mapped with 475 polymorphic markers. RESULTS: Constant Na intake resulted in a
      low heritability for Na excretion, reflecting the environmental impact (intake =
      excretion), whereas fasting revealed a gradient among RIS indicative of the
      genetic component of the traits. In the fasting state, a locus on chromosome 14
      was found to be significantly associated with K excretion (Alb, P = 0.00002, r = 
      0.69, logarithm of the odds score (LOD) 3.9), whereas another locus on chromosome
      10 (D10Cebrp97s5, P = 0.0003, r = -0.69, LOD 3.0) and one on chromosome 6
      (D6Cebrp97s14, P = 0.0007, r = -0.65, LOD 1.9) were more significantly associated
      with Na excretion and the Na/K ratio respectively. The observed correlations were
      all negative for Na, K and Na/K, indicating a higher excretion of Na and K and a
      greater Na/K ratio in rats bearing BN.Lx alleles at these loci, i.e. salt
      retention in fasting SHR. These three loci accounted for 47-55% of variance of
      their associated trait, suggesting that they are the main genetic determinants
      for these phenotypes in basal fasting conditions. Rats bearing the Y chromosome
      of SHR origin had significantly higher K excretion that, in turn, led to a
      significantly lower Na/K ratio. Finally, a locus on chromosome 7 was linked to Ca
      excretion, explaining 46% of the trait variance (D7Mit10, LOD score 3.0).
      CONCLUSION: RIS enabled us to determine QTLs for environmentally modulated traits
      such as Na, K and Ca excretions. We demonstrated that whereas urinary
      electrolytes are determined mainly by intake (environment) in a steady state,
      their excretion in an adaptive state (fasting) is predominantly genetically
      determined by distinct QTL on autosomes as well as the Y chromosome. Furthermore,
      the loci responsible for Na and K excretions act independently of the locus
      governing the relative excretion of Na/K. Thus, the salt-retaining aspects of
      some hypertensives may be, in large part, determined by genes responsible for
      renal excretion, the impact of which is predominant over the environment under
      acute challenge.

PMID- 11821706
TI  - Molecular cloning and functional characterization of the upstream rat atrial
      natriuretic peptide promoter.
AB  - OBJECTIVE: The upregulation of left ventricular atrial natriuretic peptide (ANP)
      serves as a molecular marker of cardiac hypertrophy. The precise mechanisms
      underlying this gene induction are unclear, since the presently cloned 3.6 kilo
      base (kb) rat ANP promoter failed to substantially induce coupled reporter genes
      in chronically hypertrophied hearts. The aim of this study was to clone and to
      functionally analyse the upstream ANP promoter. DESIGN: Upstream of the known ANP
      promoter, a 1.5 kb segment was cloned by the promoter walker method and found to
      harbour a putative CCAAT-binding site as well as multiple putative transcription
      factor binding sites. This newly cloned segment was ligated with a reporter gene,
      in vivo transfected into rat myocardium, and analysed under basal conditions or
      after stimulation with both acute (isovolumetric contractions in the Langendorff
      apparatus) and chronic wall stress (aortic banding). RESULTS: Reporter gene
      constructs carrying the newly cloned segment conferred only little promoter
      activity. In hearts exposed to acute wall stress, the previously cloned 3.6 kb
      ANP promoter as well as a constitutive promoter (pGL3 promoter vector) were
      active but markedly suppressed after extension with the newly cloned upstream
      promoter (-88.1 and -85.5%; P < 0.05 respectively). Site directed mutagenesis of
      two AP-2 transcription factor binding sites (base pairs -3946 to -3954 or -4192
      to -4200) eliminated this silencing effect. In hearts with chronic pressure
      overload hypertrophy as well as in normal, unstimulated hearts the activity of
      the 3.6 kb ANP promoter was weak and also abolished after ligation with the 1.5
      kb upstream segment. Moreover, both putative AP-2 binding sites within the
      upstream rat ANP promoter bound specifically to nuclear proteins of unstimulated,
      acute and chronic pressure overloaded hearts as demonstrated by electrophoresis
      mobility shift assays. CONCLUSION: Novel silencer elements were cloned, localized
      to two AP-2 binding sites in the upstream ANP promoter, and functionally
      characterized. Given that the putative upregulation of left ventricular ANP by
      the extensively studied 3.6 kb proximal promoter region is substantially
      diminished by the newly cloned segment, the functional significance of regulatory
      elements within the proximal promoter region should be re-evaluated. The
      molecular mechanism causing ANP mRNA induction in left ventricular hypertrophy
      remains obscure.

PMID- 11821707
TI  - Polymorphisms of the beta2 -adrenoceptor (ADRB2) gene and essential hypertension:
      the ECTIM and PEGASE studies.
AB  - OBJECTIVES: The beta2-adrenoceptor (ADRB2) plays a pivotal role in signalling in
      relation to hypertension and obesity. Polymorphisms of the ADRB2 gene have been
      shown to be potentially related to essential hypertension and other non
      cardiovascular disease phenotypes. We investigated whether genetic variation of
      the ADRB2 gene might be related to essential hypertension or myocardial
      infarction (MI). METHODS: Four ADRB2 gene polymorphisms C19R (T-47C), T-20C, G16R
      (G+46A), Q27E (C+79G) were investigated in two studies: PEGASE, a study of
      moderate to severe hypertension (707 cases) conducted in France, and ECTIM, a
      case-control study of MI (1178 cases, 1187 controls) conducted in France,
      Northern Ireland and Scotland. Genotyping was performed using allele-specific
      oligonucleotides. RESULTS: The ADRB2 polymorphisms T-20C and Q27E were found to
      be completely concordant, generating the haplotypes [T-20-Q27] and [C-20-E27].
      Three main haplotypes accounted for 94% of all haplotypes: [R19-G16-E27] (39%),
      [C19-R16-Q27] (35%) and [C19-G16-Q27] (20%). Haplotype frequencies were not
      significantly different between countries. Allele and genotype frequencies did
      not differ significantly between cases with essential hypertension or MI and
      control subjects. There was no association of the polymorphisms with early onset
      hypertension, blood pressure level, coronary artery stenosis or any other
      phenotype measured in these study populations. In the ECTIM Study, our
      calculation revealed that we could have detected an odds ratio (OR) for MI of 1.3
      with 80% power at a 5% type I error probability, the corresponding value for the
      PEGASE Study being an OR of 1.6 for hypertension. CONCLUSIONS: From our present
      analysis we conclude that the ADRB2 gene polymorphisms studied do not contribute
      in any important way to the risk of essential hypertension or MI in subjects of
      European ancestry.

PMID- 11821708
TI  - Sex-specific acute effect of estrogen on endothelium-derived contracting factor
      in the renal artery of hypertensive Dahl rats.
AB  - OBJECTIVE: To determine whether estrogen rapidly affects endothelium-derived
      contracting factor (EDCF) in the renal artery of hypertensive Dahl rats, and
      whether factors other than nitric oxide (NO) contribute to the effect of
      estrogen. DESIGN: Acute effects of estrogen on the acetylcholine-induced
      vasomotor responses and on prostaglandin H2/thromboxane A2 mimetic, U46619,
      induced contraction were examined in isolated arterial rings. METHODS AND
      RESULTS: Dahl salt-sensitive male and female rats were fed an 8% NaCl diet for 4
      weeks. The blood pressure increased more rapidly and to a greater extent in males
      than in females. Renal arterial rings were prepared for isometric tension
      recording. 17beta-Estradiol, but not the biologically less active stereoisomer,
      17alpha-estradiol, improved the relaxation response to acetylcholine in renal
      arteries from females. Estrogen also rapidly decreased the contraction evoked by
      acetylcholine (10(-6) to approximately 10(-4) mol/l) in renal arteries from
      females and it was effective at a physiological concentration (10(-9) mol/l) in
      the presence of Nomega-nitro-l-arginine methyl ester (an NO synthase inhibitor).
      The estrogen receptor antagonist, ICI 182,780, abolished the effect of estrogen,
      whereas the cytochrome P450 inhibitor, miconazole, had no effect. The contraction
      induced by U46619 was also suppressed by estrogen, without any contribution from
      NO. Estrogen had no effect on either relaxation or contraction responses in renal
      arteries from males. CONCLUSION: 17beta-Estradiol antagonizes increases in
      vascular tone in hypertensive females by enhancing NO-dependent relaxation, and
      by suppressing EDCF-mediated mechanisms in an NO-independent manner.

PMID- 11821709
TI  - Decreased endothelial size and connexin expression in rat caudal arteries during
      hypertension.
AB  - OBJECTIVES: Hypertension is accompanied by endothelial dysfunction. The present
      study has investigated endothelial cell morphology and connexin expression in the
      caudal artery of the rat during the development of hypertension. METHODS: A
      significant increase in systolic blood pressure was detected from 9 weeks of age
      in spontaneously hypertensive male rats (SHR) compared to normotensive Wistar
      Kyoto (WKY) rats, reaching a maximum by 11-12 weeks of age. Immunohistochemistry
      was used to quantify cell size and expression of connexins (Cxs) 37, 40 and 43 in
      the endothelium of prehypertensive (3-week-old) and hypertensive (12-week-old)
      rats. RESULTS: At 12 weeks, the size of endothelial cells and the expression of
      all three Cxs per endothelial cell were significantly less in SHR than WKY rats.
      At 3 weeks, there was no significant difference in cell size nor in the
      expression of Cxs 37 or 43; however, expression of Cx40 was significantly lower
      in SHR than in WKY rats. Between 3 and 12 weeks in WKY rats, there was no change
      in endothelial cell size, nor in the expression of Cxs 37, 40 and 43. In SHR,
      both cell size and Cx expression per endothelial cell were significantly
      decreased during the same developmental period, with a significant decrease in
      the density of Cx40 plaques. CONCLUSION: The development of hypertension in the
      SHR is accompanied by significant decreases in endothelial cell size and
      expression of Cx40, which may contribute to the endothelial dysfunction present
      in hypertension.

PMID- 11821710
TI  - Nitric oxide synthase upregulation and the predelivery blood pressure decrease in
      spontaneously hypertensive rats.
AB  - OBJECTIVE: The pregnant spontaneously hypertensive rat (SHR) exhibits a decrease
      in arterial blood pressure shortly before delivery; however, the mechanisms are
      unknown. Nitric oxide may be involved. DESIGN: Blood pressure in stroke-prone SHR
      (SHRSP) and Wistar-Kyoto control rats (WKY) was telemetrically measured. Four
      groups were studied: pregnant and non-pregnant WKY and SHRSP rats, respectively.
      Mean blood pressure in pregnant SHRSP rats decreased from 148 +/- 2 mmHg at
      conception to 120 +/- 4 mmHg at day 15, compared to 112 +/- 1 mmHg in pregnant
      WKY rats. At delivery, we determined the vasodilatory responses of isolated
      preconstricted aortic strips. RESULTS: Vasodilatory responses from late-term
      SHRSP rats were significantly greater following acetylcholine than either those
      from non-pregnant SHRSP or pregnant and non-pregnant WKY rats (acetylcholine
      IC50: 5, 22.8, 398, 1000 nmol/l, respectively), while contractile responses to
      increasing doses of norepinephrine were not different. Similar results were
      obtained with substance P. Indomethacin had no effect on the relaxation
      responses. Relaxation in response to sodium nitroprusside was not different in
      the groups. Western blot analysis showed that endothelial nitric oxide synthase
      (eNOS) levels were significantly increased in the pregnant SHRSP vessels compared
      to non-pregnant SHRSP, pregnant WKY, and non-pregnant WKY vessels. CONCLUSION:
      Increased NOS may explain the blood pressure decrease during late pregnancy in
      genetically hypertensive rats.

PMID- 11821711
TI  - Involvement of cysteinyl leukotrienes in angiotensin II-induced contraction in
      isolated aortas from transgenic (mRen-2)27 rats.
AB  - OBJECTIVES: We have previously reported that 5-lipoxygenase-derived products, and
      particularly the cysteinyl leukotrienes (CysLTs), were involved in angiotensin II
      (Ang II)-induced contractions in isolated aortas from spontaneously hypertensive
      rats. DESIGN: The aim of this study was to assess the role of CysLTs in the
      vascular response to Ang II in an Ang II-dependent model of hypertension, the
      (mRen-2)27 transgenic rats (TGs). METHODS: Intact aortic rings from TG and
      normotensive Sprague-Dawley rats (SDs) were suspended in organ chambers for
      isometric tension development in response to Ang II. In addition, the release of
      CysLTs in response to Ang II (0.3 micromol/l) was measured by enzyme immunoassay.
      RESULTS: In isolated aortas from TG rats, pretreatment with the 5-lipoxygenase
      inhibitor (AA861, 10 micromol/l) or the CysLT1 receptor antagonist (MK571, 1
      micromol/l) significantly (P < 0.05) reduced Ang II-induced contractions by 52
      and 42%, respectively. In addition, Ang II induced a 2.6-fold increase in CysLT
      release (pg/mg dry weight tissue: 58.3 +/- 17.9 (Ang II, n = 7) versus 22.5 +/-
      5.9 (basal, n = 7) P < 0.05), which was inhibited by the AT1 receptor antagonist
      losartan (1 micromol/l). In contrast, in aortas from SD rats, pretreatment with
      AA861 or MK571 did not alter Ang II-induced contraction and CysLT production
      remained unchanged after exposure to Ang II. CONCLUSION: These data suggest that
      CysLTs are involved in the contractile responses to Ang II in isolated aortas
      from TG but not from SD rats.

PMID- 11821712
TI  - Decreased arteriolar density in endothelial nitric oxide synthase knockout mice
      is due to hypertension, not to the constitutive defect in endothelial nitric
      oxide synthase enzyme.
AB  - BACKGROUND: Hypertension in endothelial nitric oxide synthase knockout (eNOS-/-)
      mice is believed to be partly due to altered vasodilatation. However, nitric
      oxide (NO) is also known to play an important part in angiogenesis. OBJECTIVE: To
      investigate whether capillary and arteriolar density were impaired in eNOS-/-
      mice, as this could account for increased vascular resistance and hypertension.
      METHODS: Using immunohistochemistry with mouse monoclonal smooth muscle alpha
      actin antibody to detect arterioles and rabbit polyclonal fibronectin antibody to
      detect capillaries, we quantified arteriolar and capillary density in the left
      ventricle and in the gracilis muscle from eNOS-/- mice compared with those in
      C57BL6J littermates (n = 6-8) in 8- and in 12-week-old mice. In a second set of
      experiments, we treated 8-week-old normotensive eNOS-/- mice with the
      antihypertensive vasodilator, hydralazine, for 1 month. RESULTS: Eight-week-old
      eNOS-/- mice were normotensive and presented similar arteriolar and capillary
      densities in cardiac and skeletal muscles compared with those in eNOS+/+ mice.
      Twelve-week-old eNOS/- mice were hypertensive (mean arterial pressure 118 +/- 21
      mmHg compared with 64 +/- 2 mmHg; P < 0.05). Capillary densities were similar in
      eNOS-/- mice and eNOS+/+ mice in the heart (4154 +/- 123 and 4051 +/- 247/mm2,
      respectively) and in skeletal muscle (961 +/- 40 and 1025 +/- 41/mm2,
      respectively). Arteriolar densities were 15% lower in skeletal muscle and in the
      heart in eNOS-/- mice than in the eNOS+/+ control group (P < 0.05). Hydralazine
      prevented hypertension and arteriolar rarefaction in eNOS-/- mice, whereas
      capillary density was unaffected by treatment with the vasodilator. CONCLUSION:
      In young non-hypertensive eNOS-/- mice, the lack of eNOS did not affect
      microvascular densities in either of the muscles studied. In adult hypertensive
      eNOS-/- mice, we observed a lower arteriolar density, but a similar capillary
      density compared with controls. Hydralazine prevented hypertension and arteriolar
      rarefaction in adult mice, suggesting a non-NO-dependent pathway. Capillary
      density was not affected by hydralazine.

PMID- 11821713
TI  - Irbesartan lowers superoxide levels and increases nitric oxide bioavailability in
      blood vessels from spontaneously hypertensive stroke-prone rats.
AB  - OBJECTIVE: To determine the effects of the angiotensin II receptor antagonist
      irbesartan, the calcium-channel blocker amlodipine, and
      hydrochlorothiazide/hydralazine on superoxide, NAD(P)H oxidase and nitric oxide
      bioavailability in spontaneously hypertensive stroke-prone rats (SHRSP). METHODS:
      Drugs or vehicle were administered for 8 weeks to SHRSP and blood pressure was
      measured weekly by tail-cuff plethysmography. After 8 weeks, superoxide levels in
      carotid arteries and aortas were measured by lucigenin chemiluminescence and
      p22phox expression quantified by immunohistochemistry. In vitro the effects of
      exposure to drugs and vehicle for 30 min and 4 h on superoxide levels and nitric
      oxide bioavailability were examined. The latter was expressed as the increase in
      contractile responses of carotid arteries to phenylephrine in the presence of the
      nitric oxide synthase inhibitor NG-nitro-l-arginine methyl ester(l-NAME).
      RESULTS: In vivo irbesartan, amlodipine and hydrochlorothiazide/hydralazine
      produced similar falls in blood pressure, from 162 +/- 4 to 125 +/- 5, 132 +/- 4
      and 131 +/- 6 mmHg, respectively, but irbesartan caused a greater reduction in
      superoxide and p22phox; superoxide levels in carotid arteries being 3.1 +/- 0.3,
      1.1 +/- 0.2, 1.9 +/- 0.3 and 2.0 +/- 0.3 nmoles/mg per min, respectively. In
      vitro 4 h exposure to irbesartan decreased superoxide levels in the aorta from
      2.08 +/- 0.68 to 1.48 +/- 0.62 nmoles/mg per min and increased nitric oxide
      bioavailability in carotid arteries. Neither 30 min incubation with irbesartan
      nor 4 h with amlodipine or hydrochlorothiazide/hydralazine altered superoxide
      levels. CONCLUSIONS: These studies support the hypothesis that AT1 receptor
      blockade has beneficial effects on superoxide production and nitric oxide
      bioavailability above that of other classes of antihypertensive agents. Reduced
      expression of components of the NAD(P)H oxidase may contribute to these effects.

PMID- 11821714
TI  - The regulation of human vascular smooth muscle extracellular matrix protein
      production by alpha- and beta-adrenoceptor stimulation.
AB  - OBJECTIVE: The sympathetic nervous system (SNS) is commonly activated in
      hypertension; however, the role of SNS activation in the pathogenesis of
      cardiovascular structural changes remains poorly defined. In particular, the
      effect of adrenergic stimulation on extracellular matrix (ECM) protein production
      by human cardiovascular cells is unknown. The present study thus investigated the
      direct effect of adrenergic stimulation on ECM protein production by cultured
      human vascular smooth muscle (VSM) cells. METHODS AND RESULTS: Exposing human VSM
      cells to norepinephrine increased collagen protein production by 42%, P < 0.01,
      when compared to control (unstimulated) cells. This effect was mediated by the
      alpha1-adrenoceptor, since it was inhibited by the selective alpha1-adrenoceptor
      antagonist; prazosin (2 micromol/l) and reproduced by the selective alpha1
      adrenoceptor agonist; phenylephrine (10 micromol/l). In contrast, beta
      adrenoceptor stimulation - isoprenaline (1 micromol/l) or norepinephrine (10
      micromol/l) + prazosin (2 micromol/l) - inhibited collagen production by 12%, P <
      0.01. This inhibitory effect was mediated via the beta1-adrenoceptor, since it
      was blocked by atenolol (beta1-adrenoceptor antagonist) but not butoxamine (beta2
      adrenoceptor antagonist). Fibronectin, another ECM protein, was similarly
      regulated by alpha- and beta-adrenoceptor stimulation. Transforming growth factor
      beta1 (TGFbeta1) mRNA expression by human VSM cells was also significantly
      influenced by adrenergic stimulation, being increased by phenylephrine (alpha
      agonist) and inhibited by isoprenaline (beta-agonist). CONCLUSIONS: These results
      uniquely demonstrate the capacity for adrenergic stimulation to directly modulate
      TGFbeta1 expression and ECM protein synthesis by the human cardiovascular system.

PMID- 11821715
TI  - Mechanisms involved in the water intake-related pressor response in the rat.
AB  - OBJECTIVE: In this study we aimed to characterize and clarify the mechanisms
      involved in the acute blood pressure increase observed concomitantly with water
      intake in moderately dehydrated rats. DESIGN: Short-term water deprivation was
      employed as a model to induce controlled water intake to study concomitant
      cardiovascular responses in the rat. METHODS: Male Wistar rats were deprived of
      water for 18-24 h before the experiments and were allowed to drink for 20 s
      periods during the experimental session. During these periods water intake was
      accompanied by steady arterial pressure increases. This pressor response was
      unaffected by topical anesthesia of the oral cavity. Direct administration of
      water into the stomach did not cause pressor responses. The pressor response was
      not affected by bilateral adrenal demedullation or by pretreatment with diazepam,
      homatropine methyl bromide, d(CH2)5 Tyr(Me)AVP, losartan or RX821002. The pressor
      response was significantly reduced by ganglionic blockade with mecamylamine or
      pretreatment with the alpha1-adrenoceptor antagonist, prazosin. CONCLUSIONS: Our
      results show that: (1) short-term dehydration can be used as a model to study
      cardiovascular responses associated with water intake in rats; and (2) the
      sympathetic nervous system and vascular smooth muscle alpha1-adrenoceptors are
      involved in the pressor response to water intake by dehydrated rats.

PMID- 11821716
TI  - Valsartan improves fibrinolytic balance in atherosclerotic rabbits.
AB  - OBJECTIVES: To examine the long-term effects of the angiotensin type I (AT1)
      receptor antagonist, valsartan, on fibrinolytic balance, coagulation parameters,
      endothelial function and structural alterations in atherosclerotic rabbits.
      METHODS: Animals were submitted to a 1% cholesterol-enriched diet for 10 weeks.
      Half of the animals were treated with valsartan (3 or 10 mg/kg per day). Systolic
      arterial pressure was directly measured in awake rabbits. Tissue plasminogen
      activator (t-PA) and tissue plasminogen activator inhibitor (PAI-1) activities
      were measured. Plasma concentrations of cholesterol, D-dimer, factor VIII and
      fibrinogen, as well as thrombin time, were also determined. Responses to
      acetylcholine, sodium nitroprusside and angiotensin II were evaluated in aortic
      rings. Morphometric analysis of aortic segments was also performed to calculate
      atherosclerotic lesion. RESULTS: Cholesterol-fed rabbits presented systolic
      arterial pressure levels comparable to controls. These animals presented aortic
      atherosclerotic lesions. Treatment with valsartan did not alter plasma
      cholesterol levels or arterial pressure in any group. Acetylcholine-induced
      relaxations and D-dimer and t-PA activity were lower (P < 0.05) in
      atherosclerotic than in normal rabbits. In contrast, PAI-1 activity was higher (P
      < 0.05) in atherosclerotic rabbits than in controls. Valsartan increased (P <
      0.05) acetylcholine-induced relaxations, D-dimer concentration and t-PA activity,
      and reduced intimal thickening and PAI-1 activity in cholesterol-fed rabbits.
      Fibrinogen concentrations and factor VIII concentrations were lower (P < 0.05)
      and thrombin time was higher (P < 0.05) in atherosclerotic rabbits compared to
      controls. Valsartan did not affect factor VIII in any group, but reduced
      fibrinogen levels only in hypercholesterolemic rabbits. Valsartan 10 mg/kg per
      day reduced (P < 0.05) thrombin time in cholesterol-fed rabbits. CONCLUSIONS:
      Impairment of fibrinolytic balance, associated with atherosclerosis in rabbits,
      appears to be related with angiotensin II via AT1receptors. The beneficial effect
      of valsartan on fibrinolysis seems to be related to the concomitant amelioration
      of endothelial dysfunction and reduction of intimal thickening, further
      supporting the importance of the blockade of angiotensin II actions to prevent
      thrombotic alterations associated with atherosclerosis.

PMID- 11821717
TI  - Peripheral blood mononuclear cell CD62L and CD11a expression and soluble
      interstitial cell adhesion molecule-1 levels following infused isoproterenol in
      hypertension.
AB  - OBJECTIVES: Increasingly, studies indicate that alterations in leukocyte and
      endothelial cell adhesion molecules may enhance atherosclerotic processes in
      human hypertension. beta-adrenergic receptor activation has long been implicated
      in the aetiology and/or maintenance of hypertension and also has significant
      effects on leukocyte and endothelial adhesion molecules. This study therefore
      examined the effects of hypertension on peripheral blood mononuclear cell CD62L
      and CD11a expression and circulating soluble interstitial cell adhesion molecule
      (ICAM)-1 (sCD54) levels following infusion of the non-specific beta-adrenergic
      agonist isoproterenol. DESIGN: In the setting of a General Clinical Research
      Center, 15 hypertensive and 20 normotensive subjects underwent an infusion of
      isoproterenol consisting of two sequential 15 min fixed-order doses of 20 and 40
      ng/kg per min. Flow cytometry was used to quantify lymphocyte and monocyte
      populations and adhesion molecules, and ELISA was used to quantify sCD54 levels.
      RESULTS: As expected, isoproterenol led to a significant increase in the number
      of circulating lymphocytes (P < 0.001) and monocytes (P < 0.01). The number of
      circulating CD3+CD8+CD62Llow T cytotoxic cells increased following isoproterenol
      (P < 0.001) and this increase was greater in hypertensives than in normotensives
      (P < 0.05). Isoproterenol led to a decrease in surface density of CD62L (P <
      0.001) and an increase in surface density of CD11a (P < 0.001) in all subjects.
      Hypertensives had a significantly lower CD62L density (P = 0.01) and higher CD11a
      density on lymphocytes (P = 0.002) compared to normotensives. sCD54 levels were
      unchanged following isoproterenol but were elevated in hypertensives (P < 0.05).
      CONCLUSIONS: A beta-adrenergic-induced environment of increased
      CD62Llow/CD11ahigh leukocytes, coupled with existing endothelial CD54 activation,
      could support basic atherosclerotic processes of increased peripheral blood
      mononuclear cell-endothelial adhesion in hypertension.

PMID- 11821718
TI  - Cilnidipine improves spontaneously hypertensive rat coronary hemodynamics without
      altering cardiovascular mass and collagen.
AB  - OBJECTIVE: The present study was designed to determine the effects of prolonged
      treatment with cilnidipine, a novel dihydropyridine calcium antagonist which
      blocks both L-type and N-type calcium channels, on systemic, regional and
      coronary hemodynamics, cardiovascular mass and collagen content in normotensive
      Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. METHODS: Male 23
      week-old WKY and SHR rats were divided into two groups for each strain. One group
      received cilnidipine (10 mg/kg per day), whereas their respective controls were
      given no therapy. Systemic and regional hemodynamics (radionuclide-labeled
      microspheres), left and right ventricular and aortic mass, and hydroxyproline
      concentration were determined after 12 weeks treatment. RESULTS: The data
      demonstrated that cilnidipine neither affected systemic hemodynamics nor
      cardiovascular mass and collagen content in WKY rats. The same treatment in the
      SHR reduced arterial pressure and total peripheral resistance without changes in
      heart rate and cardiac index. Ventricular and aortic mass indices as well as
      ventricular collagen content remained unchanged. There were no differences in
      organ blood flows between two SHR groups, whereas renal, liver and left
      ventricular coronary vascular resistances were reduced by cilnidipine. After
      dipyridamole infusion left ventricular minimal coronary vascular resistance
      decreased further in cilnidipine-treated SHR as compared with control SHR rats.
      CONCLUSION: These data suggest that cilnidipine, an L- and N- type calcium
      channel antagonist, exerted beneficial effects on coronary hemodynamics without
      altering cardiovascular mass or collagen content in SHR.

PMID- 11821719
TI  - Association of left ventricular hypertrophy with metabolic risk factors: the
      HyperGEN study.
AB  - OBJECTIVE: To determine whether combinations of metabolic risk factors (obesity,
      diabetes and hypercholesterolemia) influence the magnitude of left ventricular
      (LV) mass and prevalence of LV hypertrophy. DESIGN: Cross-sectional, relational.
      METHODS: A total of 1627 hypertensive (85.9% treated, 1036 women, 1041 African
      Americans) and 342 normotensive (180 women, 183 African Americans) participants
      in the Hypertension Genetic Epidemiology Network (HyperGEN) Study, without
      prevalent cardiovascular disease, were studied. Echocardiographic LV mass,
      normalized by height(2.7) or fat-free mass or body surface area (BSA) and the
      ratio of stroke volume to pulse pressure as a percentage of predicted (as a crude
      estimate of arterial compliance) were analyzed in relation to obesity [by body
      mass index (BMI)], central fat distribution (by waist circumference), diabetes
      (by ADA criteria) and hypercholesterolemia. RESULTS: Obesity,
      hypercholesterolemia, and diabetes were more frequent among hypertensives than
      normotensives (all P < 0.001). After controlling for age, sex, race and type and
      combination of antihypertensive medication, LV mass/height(2.7), but not LV
      mass/fat-free mass and LV mass/BSA, increased with the number of metabolic risk
      factors, both in normotensive and hypertensive participants, also after further
      adjustment for blood pressure (all P < 0.001). Stroke volume/pulse pressure also
      decreased in hypertensive, but much less in normotensive subjects, with
      increasing number of metabolic risk factors, independently of relevant
      confounders (P < 0.0001). Prevalence of LV hypertrophy was predicted by older
      age, hypertension, central fat distribution, black race and independently
      increased with the number of associated metabolic risk factors (P < 0.0001).
      CONCLUSIONS: The progressive addition of metabolic risk factors including central
      obesity, diabetes and hypercholesterolemia is associated with higher LV mass
      normalized by height(2.7), independently of hypertension and other important
      biological covariates. Obesity played a major role in this association. This
      finding indicates that LV mass is a potentially useful bioassay of strategies of
      global cardiovascular prevention.

PMID- 11821720
TI  - Persistence of antihypertensive efficacy after missed doses: comparison of
      amlodipine and nifedipine gastrointestinal therapeutic system.
AB  - OBJECTIVE: In this randomized, double-blind, crossover study, the
      antihypertensive efficacy of amlodipine and nifedipine gastrointestinal
      therapeutic system (GITS) was compared following missed doses. Design and methods
      In a randomized crossover design, 42 patients were randomized to receive
      amlodipine (5-10 mg) or the GITS formulation of nifedipine (nifedipine GITS) (30
      60 mg) once daily for 12 weeks, then vice versa. During weeks 8, 10 and 12 of
      each treatment period, compliance failures were simulated by patients missing 0,
      1 or 2 doses of their medication, and ambulatory systolic (SBP) and diastolic
      (DBP) blood pressure measurements were obtained. RESULTS: Following steady-state
      treatment (i.e. 'perfect compliance'), there was no difference between amlodipine
      and nifedipine GITS in SBP (140.1 versus 134.2 mmHg) or DBP (84.0 versus 85.8
      mmHg) at 0-24 h post-dose. When compliance was not perfect, i.e. when one or two
      doses were missed, DBP was maintained at a significantly lower level with
      amlodipine compared with nifedipine GITS at 24-48 h post-dose (83.1 versus 86.4
      mmHg, P = 0.005) and at 48-72 h post-dose (84.2 versus 89.7 mmHg, P < 0.001).
      Plasma concentrations of amlodipine were better maintained than those of
      nifedipine GITS. At 72 h post-dose, the plasma concentration of amlodipine was
      61% (17.0 +/- 11.2 ng/ml) compared with < 25% (28.3 +/- 49.9 ng/ml) for
      nifedipine GITS. CONCLUSION: During short periods of non-compliance,
      antihypertensive efficacy remains more predictable with amlodipine than with
      nifedipine GITS.

PMID- 11821721
TI  - Withdrawal from treatment in the Syst-Eur Trial.
AB  - OBJECTIVE: To investigate the reasons for withdrawal from double-blind randomized
      trials, and the reasons for changing treatment within a randomized therapeutic
      group. DESIGN: The Syst-Eur trial, in which 4695 older patients with systolic
      hypertension were randomized to active or placebo treatment. METHODS: The reasons
      for withdrawal from the trial were examined, both for patient-initiated and
      investigator-initiated withdrawals. In addition, the reasons for stopping the
      first-line treatment (nitrendipine), the second-line treatments (enalapril and
      hydrochlorothiazide) and the corresponding placebos, were determined. RESULTS: A
      total of 135 patients (6%) were withdrawn by the investigators from placebo
      treatment because their blood pressure was too high, and, similarly, 36 (1.6%)
      through patient initiation. The corresponding results for the actively treated
      patients were 14 (0.6%) and 7 (0.3%). Very few patients were withdrawn from the
      trial because of the adverse effects of treatment. However, 39 (4%) stopped
      taking active nitrendipine because of ankle oedema, compared with 4 (0.5%) on
      placebo. Similarly, 28 versus three stopped due to flushing. Forty-one (10%)
      stopped taking enalapril because of cough, against eight (2%) for enalapril
      placebo. In all, 15.0% stopped active nitrendipine, 20.2% enalapril and 6.3%
      hydrochlorothiazide, versus placebo 7.1, 9.1 and 5.1%. CONCLUSIONS: The numbers
      withdrawn from the trial for adverse treatment consequences were small in
      comparison to the cardiovascular benefits. Nevertheless the numbers stopping
      individual treatments were higher than expected.

PMID- 11821722
TI  - Comparative effects of losartan and irbesartan on serum uric acid in hypertensive
      patients with hyperuricemia and gout.

PMID- 11821723
TI  - Restoring cellular differentiatin in posttransplant lymphoproliferative disease.

PMID- 11821724
TI  - Bio-artificial liver support for acute liver failure: should we be using it to
      treat patients?

PMID- 11821725
TI  - Ventilator failure after pediatric liver transplant.

PMID- 11821726
TI  - A prospective study of rapid corticosteroid elimination in simultaneous pancreas
      kidney transplantation: comparison of two maintenance immunosuppression
      protocols: tacrolimus/mycophenolate mofetil versus tacrolimus/sirolimus.
AB  - BACKGROUND: We examined the feasibility of rapid corticosteroid elimination in
      simultaneous pancreas kidney transplantation. METHODS: Forty consecutive
      simultaneous pancreas-kidney (SPK) transplant recipients were enrolled in a
      prospective study in which antithymocyte globulin induction and 6 days of
      corticosteroids were administered along with tacrolimus and MMF (n=20) or
      tacrolimus and sirolimus (n=20). Mean+/-SD follow-up for recipients receiving
      tacrolimus/MMF and tacrolimus/sirolimus were 12.7+/-3.9 and 13.4+/-2.9 months,
      respectively. Patient and graft survival, and rejection rates were compared to an
      historical control group (n=86; mean follow-up 41.5+/-15.4 months) of SPK
      recipients that received induction and tacrolimus, MMF, and corticosteroids.
      RESULTS: Demographic characteristics of recipient and donor variables were
      similar among all groups. The 1-year actuarial patient, kidney, and pancreas
      survival rates in the 40 SPK transplant recipients with rapid corticosteroid
      elimination were 100, 100, and 100%, respectively. In the historical control
      group the 1-year actual patient, kidney, and pancreas survival rates were 96.5,
      93.0, and 91.9%, respectively. The 1-year rejection-free survival rate recipients
      in the rapid steroid elimination group collectively was 97.5 vs 80.2% in the
      historical control group (P=0.034). At 6 and 12 months posttransplant the serum
      creatinine values remained stable in all groups. CONCLUSIONS: We conclude that
      chronic corticosteroid exposure is not required in SPK transplant recipients
      receiving antithymocyte globulin induction and maintenance immuno-suppression
      consisting of either tacrolimus and mycophenolate mofetil or tacrolimus and
      sirolimus.

PMID- 11821727
TI  - Potentiating the benefit of vascular-supplied glutamine during small bowel
      storage: importance of buffering agent.
AB  - BACKGROUND: Glutamine (gln)-supplemented University of Wisconsin (UW) solution
      improves overall small bowel (SB) preservation. Sustained gln metabolism in a
      system devoid of hepatic detoxification will necessarily result in the
      accumulation of pH active end products leading to nonphysiologic pH shifts. We
      hypothesized that simultaneous addition of N,N-bis[2-hydroxyethyl]-2-aminoethane
      sulfonic acid (BES), a known buffering agent, would potentiate the beneficial
      effect of gln supplementation by addressing the fundamental metabolic principle
      of pH homeostasis. METHODS: Sprague-Dawley SB rats were administered a vascular
      flush with one of four solutions: UW; UW+90 mM BES (UWB); UW+2% gln (UWG); or
      UW+2% gln+90 mM BES (UWBG). Indices of energetics, barrier function, gln
      catabolism, and histology (light and electron microscopy) were assessed over a 10
      hr cold storage time course. RESULTS: Superior gln utilization in the UWBG group
      was indicated by elevated levels of key catabolites (glutamate, aspartate,
      glycine, ammonia). The addition of BES and gln resulted in significantly higher
      levels of all energetic parameters (ATP, total adenylates) at 10 hr compared with
      UW, UWB, and/or UWG. Barrier function was markedly improved after 10 hr storage
      in the UWBG group; mannitol permeability was 169 nmol/cm2/hr versus 572 and 445
      nmol/cm(2)/hr (for UW and UWG, respectively). Histologic injury at 10 hr was 5.5,
      7.5, and 8 (Park's grade) for UWBG, UWG, and UW. Ultrastructural damage was
      markedly reduced with UWBG, as assessed by grade of mitochondria damage.
      CONCLUSION: This study strongly supports that the beneficial effects of gln
      enriched UW solution can be amplified when combined with an effective buffering
      agent such as BES.

PMID- 11821729
TI  - Reduction of human-to-pig cellular response by alteration of porcine MHC with
      human HLA DPW0401 exogenes.
AB  - BACKGROUND: In pig-to-human discordant xenotransplantation, the xenograft can be
      rejected by a formidable human xenogenic T-cell response, even if the graft has
      gone through hyperacute rejection or delayed xenograft rejection (acute vascular
      rejection). We therefore examined, in this study, whether the human-to-pig
      cellular response could be attenuated through the generation of a transgenic pig
      for human HLA II. METHODS: With the technique of microinjection, we produced the
      HLA DPw0401 transgenic pig. The expression of the HLA DPw0401 gene on peripheral
      blood mononuclear cells (PBMCs) of the transgenic pig was examined by reverse
      transcriptase-polymerase chain reaction and flow cytometry. The antigenicity of
      the transgenic HLA DPw0401 molecule was tested by the HLA DPw0401-primed
      lymphocyte test reagent. The cellular response was analyzed by xenogenic mixed
      lymphocyte culture. RESULTS: The mRNA and protein of HLA DPw0401 were expressed
      in the PBMCs of the transgenic pig. The PBMCs of the HLA transgenic pig induced a
      stronger cellular reaction to HLA DPw0401-primed lymphocyte test reagents than
      the nontransgenic littermate pig (n=7, P<0.01). In direct xenogenic mixed
      lymphocyte culture with responders from HLA DPw0401(+) humans, the PBMCs from the
      HLA DPw0401 transgenic pig, as compared with those from the normal pig, induced a
      lower degree of xenogenic cellular response to human PBMCs (n=4, P=0.08).
      CONCLUSIONS: Our preliminary data demonstrated the possibility that the human HLA
      DPw0401 phenotype can be transferred onto porcine cells through the generation of
      HLA transgenic pigs and make the PBMCs of humans more tolerant to porcine cells.

PMID- 11821728
TI  - Indirect recognition and antibody production against a single mismatched HLA-A2
      transgenic molecule precede the development of obliterative airway disease in
      murine heterotopic tracheal allografts.
AB  - BACKGROUND: Previous studies have implicated the allogeneic immune response in
      the development of obliterative bronchiolitis after lung transplantation.
      However, the progression of specific pathogenic events leading to this form of
      chronic allograft dysfunction have not been well characterized. We used a murine
      tracheal transplantation model in which a single mismatched HLA-A2-transgenic
      molecule is indirectly recognized by the recipient CD4(+) T cells to show that
      obliterative airway disease (OAD) that developed in these allografts was preceded
      by indirect recognition of the HLA-A2 molecule and subsequent development of anti
      HLA-A2 antibodies. METHODS: Tracheas from HLA-A2(+) C57BL/6 mice were
      heterotopically transplanted into C57BL/6 mice. Allograft histopathology as well
      as anti-HLA-A2 T-cell proliferative responses and anti-HLA-A2 antibody
      development were determined at days 5, 10, 20, and 28 after transplantation.
      RESULTS: All of the HLA-A2(+) tracheal allografts transplanted into C57BL/6
      recipients demonstrated complete development of OAD by day 20. Spleen cells from
      the mice that underwent transplantation demonstrated significant proliferation
      against HLA-A2(+) cells by day 5. Indirect recognition of HLA-A2-derived peptides
      by spleen cells from allograft recipients was also higher on days 5 and 10 as
      compared with irrelevant peptides derived from HLA-A1, HLA-A3, and HLA-B44.
      Allograft recipients showed detectable levels of anti-HLA-A2 antibodies by day 5
      and full development of anti-HLA-A2 antibodies by day 20. CONCLUSION: These
      results show that sensitization of CD4+ T cells against the mismatched HLA-A2
      alloantigen precedes the development of anti-HLA antibodies as well as OAD,
      suggesting an important role for alloreactive CD4(+) T-cell activation and
      alloantibody development in the immunopathogenesis of OAD.

PMID- 11821730
TI  - Duodenal histology for monitoring treatment of acute rejection in
      pancreaticoduodenal allografts in rats.
AB  - BACKGROUND: Although the value of duodenal histology as a means to diagnose acute
      rejection in pancreaticoduodenal allografts has been validated, it is not known
      how the duodenum responds to antirejection treatment in comparison with the
      pancreas. METHODS: Diabetic Lewis rats received a pancreaticoduodenal allograft.
      Cyclosporine was given for 5 days and then discontinued for 2 days (group 1), for
      4 days (group 2), for 6 days (group 3), for 8 days (group 4), for 9 days (group
      5), and for 10 days (group 6). Two animals of each group were killed for
      histology at the end of immunosuppressive-free intervals. In the remaining rats,
      rejection was treated with methylprednisolone on 3 consecutive days. Duodenal
      histology was compared with pancreatic morphology before and after treatment of
      rejection. RESULTS: Duodenal histology had a positive and negative predictive
      value of 100% for detection of acute rejection in the pancreatic portion of the
      graft. After antirejection treatment, duodenal morphology was however less
      accurate (positive predictive value, 96%; negative predictive value, 67%). The
      Spearman correlation coefficient (p) of duodenal and pancreatic rejection grades
      was higher before antirejection treatment (p=1.0) than thereafter (p=0.724).
      Considering interstitial and vascular changes separately, vascular rejection
      correlated to a higher extent than interstitial rejection between the two
      portions of the graft (p=0.725 vs. p=0.677). CONCLUSIONS: Duodenal histology
      accurately predicts the initial diagnosis of rejection of the pancreas. However,
      after treatment of acute rejection, duodenal morphology is more likely to recover
      from rejection than the pancreas. Awareness of this phenomenon might be important
      for the interpretation of duodenal follow-up biopsies.

PMID- 11821731
TI  - Assessment of the AMC-bioartificial liver in the anhepatic pig.
AB  - BACKGROUND: The anhepatic pig model was used to evaluate a bioartificial liver
      developed in our institution (AMC-BAL). The bioartificial liver is based on
      oxygenated plasma perfusion of porcine hepatocytes attached to a polyester
      matrix. METHODS: Pigs (n=15) underwent total hepatectomy with restoration of
      caval continuity using a polyethylene, three-way prosthesis. In group I, pigs
      received limited intensive care under continuation of general anesthesia (n=5).
      Group II pigs (n=5) underwent, in addition, extracorporeal plasma perfusion of an
      AMC-BAL without hepatocytes (device control group). In group III (n=5), plasma
      perfusion occurred with an AMC-BAL loaded with autologous hepatocytes. Groups II
      and III were connected to the extracorporeal system 24 hr after hepatectomy, for
      a period of 24 hr. The main outcome parameters were as follows: survival time,
      liver enzymes (aspartate aminotransferase, alanine aminotransferase), blood
      ammonia, and total/direct bilirubin. RESULTS: Survival (mean +/- SD) of the
      anhepatic pigs was significantly increased in the BAL-treated group (group III:
      65+/-15 hr), as compared with the control groups (group I: 46+/-6 hr and group
      II: 43+/-14 hr). Mean blood ammonia levels during BAL treatment were
      significantly lower in the BAL-treated group in comparison with both control
      groups (P=0.02). Total and direct bilirubin levels gradually increased after
      hepatectomy and reached maximum values of 1.98 mg/dl and 1.50 mg/dl,
      respectively, showing no differences between the three groups. CONCLUSIONS: (1)
      Treatment of anhepatic pigs with the AMC-BAL containing autologous hepatocytes
      significantly increases survival time, which is associated with a significant
      decrease in blood ammonia. 2) Anhepatic pigs demonstrate increasing direct
      bilirubin levels as a result of extrahepatic bilirubin conjugation.

PMID- 11821732
TI  - The immune response to corneal allograft requires a site-specific draining lymph
      node.
AB  - BACKGROUND: Recent studies have shown that head-neck draining lymph nodes (DLN)
      are required for priming the immune response during corneal allograft rejection.
      In this study we have investigated further the role of the DLN and spleen in
      corneal graft rejection in mice. METHODS: Individual DLN (submandibular [SM];
      superficial cervical [SC]; and internal jugular) or their combinations were
      removed in mice undergoing corneal allografting (C57BL/10, H2(b) to BALB/c,
      H2(d)). In some mice, DLN from syngeneic mice were retransplanted, whereas other
      mice underwent removal of the spleen before corneal allografting. In a high-risk
      group of mice, removal of the DLN before a second corneal graft procedure was
      performed. RESULTS AND CONCLUSIONS: The data show that a single specific lymph
      node, i.e., the SM node, is the major DLN involved in corneal graft rejection
      whereas its nearest neighbor, the SC DLN, not only cannot substitute for the SM
      node in priming the immune response but may be involved with the spleen in immune
      privilege. Retransplantation studies of syngeneic LN indicate that the site of
      the DLN is more important to the process of graft rejection than the specific DLN
      tissue. This applies to the DLN whether it contains naive or memory allospecific
      T cells as shown in experiments in which removal of the SM DLN from mice who had
      already been primed by a previous corneal graft, prevented rejection of a second
      corneal graft in the same strain combination.

PMID- 11821733
TI  - The antineoplastic drug Paclitaxel has immunosuppressive properties that can
      effectively promote allograft survival in a rat heart transplant model.
AB  - INTRODUCTION: Recurrent and de novo neoplasms are ominous risk factors for
      transplant patients. In particular, when organ transplantation is attempted to
      cure isolated cancers, conventional immunosuppression likely promotes cancer
      reestablishment. Therefore, drugs with both immunosuppressive and antineoplastic
      activity are needed. We show that the anticancer agent paclitaxel may fulfill
      these diverse expectations. METHODS: Heterotopic heart transplantation was
      performed in the ACI-to-Lewis or Lewis-to-ACI rat-strain combination and
      paclitaxel was injected i.p. daily (days 0-14) at doses from 0.75-1.5 mg/kg.
      Serum cytotoxic antidonor antibody levels were measured using a complement
      mediated cell cytotoxicity assay. In vitro, the effect of paclitaxel on Lewis
      lymphocyte viability and apoptosis was determined. Also, Lewis lymphocytes
      preconditioned with irradiated ACI cells+/-paclitaxel, were restimulated with ACI
      cells and tested for cytotoxic T cell (CTL) activity and interleukin-2 (IL-2)
      production. RESULTS: Paclitaxel promoted heart allograft survival in a dose
      dependent manner in both high- and low-responder transplant combinations.
      Furthermore, low-doses of paclitaxel (0.75-1.0 mg/kg) and cyclosporine (1 mg/kg)
      in combination synergistically increased transplant survival. Immunologically,
      paclitaxel markedly reduced the antidonor cytotoxic antibody response. In vitro,
      nearly 90% of prestimulated lymphocytes were killed by paclitaxel and cells
      became positive for the apoptosis marker, annexin-V. Furthermore, paclitaxel
      reduced CTL activity and IL-2 production after alloantigen rechallenge.
      CONCLUSION: Paclitaxel, a clinically proven antineoplastic agent, also has potent
      immunosuppressive properties in rodent organ transplantation. This drug could be
      extremely valuable in transplant situations where de novo cancer develops, or
      when organ transplantation is performed to treat isolated, but typically
      recurrent, neoplasms.

PMID- 11821734
TI  - Benefit of transplantation in primary biliary cirrhosis between 1985-1997.
AB  - BACKGROUND: In the 1980s, primary biliary cirrhosis (PBC) patients were shown to
      benefit from transplantation when compared to a mathematical model. This study,
      using the same model, evaluates a cohort of patients who underwent
      transplantation in the late 1980s and early 1990s before and after the
      introduction of therapy with ursodeoxycholic acid (UDCA). METHODS: All 73 PBC
      patients transplanted at the University of Toronto between 1985 and 1997 were
      included in the study. Actual survival posttransplantation, calculated with the
      Kaplan-Meier product-limit estimator, was compared to predicted survival without
      transplantation, as determined by the Mayo model. The effect of UDCA therapy on
      outcome was studied by dividing the cohort into those transplanted before and
      after 1992, the year in which UDCA use for PBC was introduced. RESULTS: At 2
      years posttransplant, predicted survival without transplant was 55% whereas
      actual survival was 79%. At 7 years posttransplant, these figures were 22% and
      68%, respectively (P=3 x 10(-8)). There was a nonsignificant trend towards
      improved survival in those transplanted during the UDCA era compared to those
      transplanted in the pre-UDCA era. CONCLUSIONS: Liver transplantation remains
      extremely beneficial for patients with end-stage PBC. There was no difference in
      outcome after liver transplantation in those transplanted during the UDCA era
      when compared to their pre-UDCA counterparts.

PMID- 11821735
TI  - Diaphragmatic dysfunction after pediatric orthotopic liver transplantation.
AB  - BACKGROUND: Pediatric orthotopic liver transplantation (OLT) has a low mortality.
      Some children, however, have an adverse outcome defined as a prolonged
      ventilatory support requirement and protracted pediatric intensive care unit
      (PICU) stay. The aim of this study was to determine if that adverse outcome
      related to the child's condition pre-OLT and/or the development of a pleural
      effusion or diaphragmatic dysfunction. METHODS: The study included 210 children
      with a median age at transplantation of 45.5 months (range 0.2-252 months).
      Fourteen had undergone retransplantation. The duration of ventilatory support
      (intermittent positive pressure ventilation [IPPV]) and PICU admission and
      development of a pleural effusion and/or diaphragmatic dysfunction were
      documented for each child. The patients were divided into three groups according
      to whether they had acute liver failure (ALF), chronic liver disease at home
      (CHOM), or chronic liver failure sufficiently ill to be in the hospital awaiting
      transplantation (CHOSP). RESULTS: The 36 children with ALF were of similar age to
      the 138 CHOM and 36 CHOSP children but required longer IPPV (P<0.0001) and PICU
      stay (P<0.0001). Overall, 17 children developed diaphragmatic dysfunction and 138
      pleural effusions; affected children required longer IPPV and PICU stay (P<0.01).
      Regression analysis demonstrated that diaphragmatic dysfunction, but not pleural
      effusion development, was associated with prolonged ventilation (P<0.01) and
      protracted PICU stay (P<0.05). Other risk factors were ALF (P<0.01),
      retransplantation (P<0.01), and young age (P<0.05). CONCLUSION: Diaphragmatic
      dysfunction adversely influences PICU morbidity after OLT. Early assessment of
      diaphragmatic function, and if necessary aggressive management, might improve
      outcome.

PMID- 11821736
TI  - Long-term kidney graft survival across a positive historic but negative current
      sensitized cross-match.
AB  - BACKGROUND: The sensitive cross-match (XM) techniques that have been introduced
      for clinical transplantation can detect anti-donor immune reactivity despite a
      negative standard National Institute of Health (NIH) cross-match. One of them
      uses anti-kappa human light chain globulins (AHG). But there is some discussion
      about the clinical consequences of a positive AHG-XM in the historical sera that
      became negative in the sera collected just before the transplantation
      (pretransplant sera). This study was intended to assess the risk of kidney graft
      failure associated with a positive historic but negative pretransplant AHG-XM in
      allosensitized patients having a negative historic NIH-XM. METHODS: This
      retrospective study includes 90 consecutive renal transplants in immunized
      patients performed at one center between 1985 and 1991. All of the patients had
      negative historical and pretransplant standard NIH lymphocytotoxic cross-matches
      and received the same immunosuppressive regimen. The AHG-XMs were done
      retrospectively using peak historic and sera collected on the day of the
      transplantation. RESULTS: The AHG cross-match (AHG-XM) was positive in 17
      patients, although the standard NIH cross-match was negative. Fourteen of them
      had a positive historical but negative pretransplant AHG-XM. The actuarial graft
      survival in this group of 14 patients was 100% at 1 year and 78% at 9 years
      compared with 90 and 67%, respectively, in patients with negative historical AHG
      XM. In addition, the number of rejection episodes per patient as well as renal
      function at 1, 2, and 5 years were similar in the two groups. IgG anti-donor HLA
      class I accounted for the XM positivity in 12 of the 14 patients; most rapidly
      lost all antibody reactivity by NIH technique in an average time of 8 months
      before the transplantation. In conclusion, this study suggests that transplant
      patients having a negative historic NIH-XM but a positive historic AHG-XM may not
      be at high risk of graft failure especially if there is a well-documented sera
      history showing a marked decrease in PRA level before transplantation and a
      negative pretransplant AHG-XM.

PMID- 11821737
TI  - Three-dimensional multislice helical computed tomography with the volume
      rendering technique in the detection of vascular complications after liver
      transplantation.
AB  - BACKGROUND: Hepatic artery stenosis and thrombosis are common complications in
      liver transplant patients. Digital subtraction angiography (DSA) has served as
      the gold standard to make this diagnosis. More recently, three-dimensional
      helical computed tomographic arteriography (3D CTA) with maximum intensity
      projection and shaded surface display techniques has been compared with DSA. The
      purpose of this study was to determine whether 3D CTA with the volume rendering
      technique is a useful and accurate tool in the detection of vascular
      complications after liver transplantation. METHODS: Thirty-five consecutive liver
      transplant patients underwent 3D CTA with volume rendering technique. The
      standard of reference was DSA for 20 patients and imaging and clinical follow-up
      for 15 patients. Two blinded reviewers evaluated the axial and 3D CTA images in
      consensus. RESULTS: 3D CTA with volume rendering technique detected 10 hepatic
      artery stenoses, six hepatic artery thromboses, two hepatic artery
      pseudoaneurysms, two splenic artery aneurysms, two portal vein stenoses, and four
      redundant hepatic arteries. In one case computed tomography (CT) detected a
      moderate hepatic artery stenosis, while conventional angiography showed a normal
      artery. The sensitivity of CT for detecting vascular lesions was 100%,
      specificity was 89% (8 of 9), accuracy was 95% (19 of 20), positive predictive
      value was 92% (11 of 12), and negative predictive value was 100% (8 of 8).
      CONCLUSIONS: 3D CTA is a useful and accurate noninvasive technique for detection
      of vascular complications in liver transplant patients.

PMID- 11821738
TI  - The significance of parenchymal changes of acute cellular rejection in predicting
      chronic liver graft rejection.
AB  - BACKGROUND: Chronic rejection (CR) in liver allografts shows a rapid onset and
      progressive course, leading to graft failure within the first year after
      transplantation. Most cases are preceded by episodes of acute cellular rejection
      (AR), but histological features predictive for the transition toward CR are not
      well documented. METHODS: We assessed the predictive value of centrilobular
      necrosis, central vein endothelialitis (CVE), central vein fibrosis, and lobular
      inflammation in the development of CR. One-week and one-month biopsy specimens of
      12 patients with CR were compared with those of a control group consisting of 17
      patients, who experienced AR without developing CR. The progress of the
      histological changes was further evaluated in follow-up biopsy specimens of the
      CR group taken at 2 months and beyond 3 months after transplantation. RESULTS:
      Centrilobular necrosis, CVE, central vein fibrosis, and lobular inflammation were
      common features in both groups at 1 week. At 1 month, the incidence declined in
      the control group. The CR group showed an increased incidence and persistence of
      these features in the follow-up biopsy specimens. The incidence and median grade
      of severity of CVE was significantly higher in the CR group (P=0.04 and P<0.001).
      The severity of portal and lobular inflammation was also more pronounced in the
      CR group (P=0.01 and 0.068). Conversely, in the control group, the incidence of
      the lobular features decreased and the severity of CVE declined significantly
      (P=0.03). CONCLUSION: The shift from a predominantly portal-based process toward
      lobular graft damage represents the early transition of AR to CR, for which a
      modification of immunosuppression might be necessary to prevent graft loss.

PMID- 11821739
TI  - Gender imbalance in living donor renal transplantation.
AB  - BACKGROUND: Previous studies have shown more women than men among living donors
      (LD) and more men among recipients of those kidneys. In this study, we compared
      the evolving demographics of LD transplants. METHODS: We retrospectively analyzed
      all LD transplants performed in our center between 1964 and 2000. RESULTS: Among
      1182 LD cases, 1035 (88%) were biologically related (LRD) and 147 (12%) were
      unrelated (LURD). LURD donors and recipients were significantly older than LRD
      donors and recipients, respectively (P=0.0001). More LURD allograft recipients
      were male (71%) compared with LRD recipients (57%) (P=0.0013). The proportion of
      female donors was 55% in both groups. Spousal donations were predominantly wife
      to-husband (69%). Compared with the LRD group, there was a greater proportion of
      female-to-male LURD transplants (46 vs. 30%) and a smaller proportion of female
      to-female LURD transplants (10 vs. 25%) (P=0.0001). When spousal pairs were
      excluded from the analysis, there was a higher proportion of male-to-male (48 vs.
      27%) donations and a lower proportion of male-to-female (18 vs. 9%) and female-to
      female (25 vs. 17%) transplants in the LURD group (P=0.001). CONCLUSIONS: Gender
      disparities in LD transplantation are primarily due to a higher proportion of
      wife-to-husband donations and a lower incidence of male-to-female grafts among
      nonspousal LURD transplants. Strategies should be devised to ensure access for
      women to renal transplantation and to encourage and facilitate donation by men.

PMID- 11821740
TI  - Centrilobular necrosis in children after combined liver and small bowel
      transplantation.
AB  - BACKGROUND: Centrilobular necrosis is not an uncommon finding after isolated
      liver transplantation. In this study, we sought to describe hepatic centrilobular
      necrosis in children after combined liver and small bowel transplantation (LSBT),
      and to assess the predictive factors, possible causes, and prognosis. METHODS:
      Six children aged 4 to 11 years, in whom liver biopsy showed centrilobular
      necrosis at least once, 3 weeks to 2 years after LSBT, were compared with nine
      children without this pathology. All six children experienced an acute
      complication in the few weeks preceding the finding of centrilobular necrosis. In
      addition, one child had an early arterial thrombosis and one, severe colitis 3
      years after LSBT. RESULTS: Centrilobular necrosis was associated with
      centrilobular swelling, dropout, endotheliitis, and inflammation. Fibrosis
      developed early and worsened on follow-up biopsy in three children. Portal
      symptoms of acute rejection were not constant, and there was no ductopenia.
      Biologic abnormalities were responsive to increased immunosuppression, including
      mycophenolate in four cases. However, follow-up biopsies showed persistent
      lesions in five patients, mildly inflammatory in four. Baseline immunosuppression
      had to be maintained at high levels. No viral infections, vascular compromise
      (except in one), and autoimmunity were found. We compared the two groups of
      children for initial diagnosis, age at transplantation, time receiving parenteral
      nutrition, ischemic time, presence of an associated transplanted colon, number of
      reoperations and infections, intestinal rejection, and immunosuppression, and
      found no differences. CONCLUSIONS: This severe manifestation of chronic liver
      rejection occurred despite the heavy immunosuppression needed for LSBT. The
      previous acute clinical event could have triggered rejection by modifying the
      effective immunosuppression at the tissue level. Despite high baseline
      immunosuppression, histologic lesions persisted and significant fibrosis
      developed in half the children. We speculate that the lack of induction of
      tolerance in this particular setting of LSBT could be responsible for constant
      immune stimulation, thus chronic rejection. The optimal protocol of
      immunosuppression has yet to be defined to avoid this complication.

PMID- 11821741
TI  - Neurological improvement during bioartificial liver sessions in patients with
      acute liver failure awaiting transplantation.
AB  - BACKGROUND: Brain edema is the main cause of death in acute liver failure
      patients awaiting transplantation. We assessed the HepatAssist 2000, a liver
      assist system containing porcine hepatocytes, as a bridge to transplantation in
      patients with acute liver failure. METHODS: Thirteen patients suffering from
      acute liver failure with criteria for transplantation entered an open baseline
      controlled study, with liver-assist treatment sessions at 24-hr intervals until
      transplantation. Neurological status was regularly evaluated using the Glasgow
      Coma Scale. RESULTS: Three patients were not treated: one had an immediate
      transplantation and two improved spontaneously. Ten patients received one to
      three courses of HepatAssist. A significant neurological improvement (mean
      Glasgow Coma Scale before and after treatment: 6.5+/-3.7 and 9.6+/-4.4,
      respectively, P<0.02) was observed, which was related to the volume of plasma
      processed per square meter of body surface. A significant decrease was observed
      in mean levels of bilirubin (P=0.0005) and transaminases but not in the other
      indicators of liver function. Six patients had transient episodes of hemodynamic
      instability, and five had bleeding complications. Two patients died after
      transplantation. Eight patients survived with a mean follow-up of 24.3 (18-32)
      months. CONCLUSION: The HepatAssist 2000 is well tolerated, improves cerebral
      function, and may be used as a bridge to transplantation for patients with liver
      failure.

PMID- 11821742
TI  - Influence of host-recipient origin on clinical aspects of posttransplantation
      lymphoproliferative disorders in kidney transplantation.
AB  - BACKGROUND: Posttransplantation lymphoproliferative disorder (PTLD) is a well
      known complication of immunosuppression associated with solid organ
      transplantation. The donor or host origin of PTLD may influence the outcome of
      the disease as it has been reported that a donor origin may be associated with a
      better prognosis. The aim of the study was to determine the origin (recipient or
      donor) of 12 PTLD occurring in kidney transplant recipients and to correlate the
      results with clinical findings. METHODS: Origin of PTLD was determined using HLA
      DRB1 molecular typing, analysis of multiple short-tandem repeat microsatellite
      loci, and HLA class I antigen expression by immunohistochemistry. RESULTS:
      Combining the three techniques, we found that eight cases originated from the
      recipient and four cases originated from the donor. The results of the three
      techniques were concordant and altogether assigned the origin of the tumors. All
      the donor-origin PTLD were strictly localized to the kidney graft, developed
      after a mean time of 5 months after transplantation, and regressed after
      reduction of immunosuppression. In contrast, seven of the eight recipient-origin
      PTLD presented as multisystemic disease, occurred a mean time of 75.7 months
      after the transplantation, and had a worse outcome (mortality, five deaths of
      eight patients, 62.5%). CONCLUSIONS: These results suggest that PTLD originating
      from the donor arise in the first year after transplantation into the graft, and
      that recipient-origin PTLD develop later as an invasive disease. Because it
      permits simultaneously the analysis of cell morphology and tumor origin,
      immunohistochemistry is a more reliable technique in the case of graft tumors
      associated with allograft rejection. The determination of the origin of the
      tumors seems to be of value in the management of PTLD to predict the outcome and
      to adapt therapy.

PMID- 11821743
TI  - A histone deacetylase inhibitor, azelaic bishydroxamic acid, shows cytotoxicity
      on Epstein-Barr virus transformed B-cell lines: a potential therapy for
      posttransplant lymphoproliferative disease.
AB  - BACKGROUND: Posttransplant lymphoproliferative disease (PTLD), driven by the
      presence of Epstein-Barr virus (EBV), is becoming an increasingly important
      clinical problem after solid organ transplantation. The use of immunosuppressive
      therapy leads to the inhibition of the cytotoxic T cells that normally control
      the EBV latently infected B cells. The prognosis for many patients with PTLD is
      poor, and the optimal treatment strategy is not well defined. METHOD: This study
      investigates the use of a histone deacetylase inhibitor, azelaic bishydroxamic
      acid (ABHA), for its ability to effectively kill EBV-transformed lymphoblastoid
      cell lines. RESULTS: In vitro treatment of lymphoblastoid cell lines with ABHA
      showed that they were effectively killed by low doses of the drug (ID50 2-5
      microg/ml) within 48 hr. As well as being effective against polyclonal B-cell
      lines, ABHA was also shown to be toxic to seven of eight clonal Burkitt's
      lymphoma cell lines, indicating that the drug may also be useful in the treatment
      of late-occurring clonal PTLD. In addition, ABHA treatment did not induce EBV
      replication or affect EBV latent gene expression. CONCLUSION: These studies
      suggest that ABHA effectively kills both polyclonal and clonal B-cell lines and
      has potential in the treatment of PTLD.

PMID- 11821744
TI  - Indirect allorecognition can play an important role in the development of
      transplant arteriosclerosis.
AB  - BACKGROUND: Indirect allorecognition has been implicated in the initiation of
      chronic allograft dysfunction. Our aim was to develop an animal model that
      allowed the contribution of the direct and indirect pathway of allorecognition in
      the evolution of transplant arteriosclerosis, the main feature of chronic
      allograft rejection, to be evaluated. METHODS: Aortic allografts mismatched for a
      single MHC class I antigen were transplanted into athymic NUDE or RAG (-/-) mice.
      Immunodeficient mice were reconstituted with either CD4(+) (indirect) or CD8(+)
      (direct + indirect) T cells in the presence or absence of depleting antibodies
      specific for the opposite T-cell subset. Aortic grafts were analyzed by
      performing morphometry, immunohistochemistry, and quantitative reverse
      transcriptase-polymerase chain reaction for the detection of cytokine mRNA
      production. Donor-specific alloantibody production was measured by fluorescence
      activated cell sorter analysis. RESULTS: Reconstitution of athymic nude mice with
      4 x 10(7) purified CD4(+) T cells resulted in vascular rejection of MHC class I
      mismatched aortic grafts. Intimal proliferation was 24+/-8% and did not decrease
      when nude-derived endogenous CD8(+) T cells were depleted from the nude
      recipients (intimal proliferation, 21+/-7%). Transplant arteriosclerosis
      initiated by CD4+ T cells was associated with the presence of intragraft mRNA for
      interferon-gamma, tumor necrosis factor-alpha, inducible nitric oxide synthase,
      and interleukin 12. Reconstitution of RAG-1(-/-) mice with 4 x 10(7) purified
      CD4(+) T cells resulted in a similar degree of transplant arteriosclerosis
      (intimal proliferation, 20+/-9%) in MHC class I mismatched aortic grafts in the
      absence of alloantibody production. CONCLUSION: Indirect recognition of donor MHC
      class I molecules by CD4(+) T cells can play an important role in the process of
      transplant arteriosclerosis. CD8(+) T-cell effector function and alloantibody
      production in this model are dependent on CD4(+) T-cell help after indirect
      allorecognition.

PMID- 11821745
TI  - Heme oxygenase-1 overexpression protects rat hearts from cold
      ischemia/reperfusion injury via an antiapoptotic pathway.
AB  - BACKGROUND: Ischemia/reperfusion (I/R) injury is one of the most important causes
      of the early graft loss. We have shown that overexpression of heme oxygenase-1
      (HO-1), an inducible heat shock protein 32, protects rat livers against I/R
      injury. We report on the cytoprotective effects of HO-1 in a rat cardiac I/R
      injury model, using cobalt protoporphyrin (CoPP) as HO-1 inducer and zinc
      protoporphyrin (ZnPP) as HO-1 inhibitor. METHODS: Three groups of Lewis rats were
      studied: group 1 control donors received phosphate-buffered saline 48 hr before
      the harvest; group 2 donors were pretreated with CoPP at -48 hr; and in group 3,
      donors received CoPP at -48 hr and ZnPP was given to recipients at reperfusion.
      Hearts were harvested, stored in University of Wisconsin solution (4 degrees C)
      for 24 hr, and then transplanted to syngeneic (Lewis) rats. RESULTS: Sixty
      percent of control grafts ceased their function in <15 min. In contrast, 80% of
      CoPP-pretreated grafts survived 14 days. All grafts stopped functioning within 24
      hr after CoPP + ZnPP therapy. Cardiac HO-1 enzymatic activity and protein
      expression correlated with beneficial effects of CoPP and deleterious effects of
      adjunctive ZnPP treatment. Markedly less apoptotic (TUNEL+) myocyte/endothelial
      cells could be detected in CoPP cardiac grafts, as compared with controls. The
      expression of antiapoptotic (Bcl-2/Bag-1) proteins was up-regulated in the CoPP
      group. CONCLUSION: HO-1 overexpression provides potent protection against cold
      I/R injury in a stringent rat cardiac model. This effect depends, at least in
      part, on HO-1-mediated up-regulation of a host antiapoptotic mechanism,
      especially in the early postreperfusion period.

PMID- 11821746
TI  - CTLA4ig induces long-term graft survival of allogeneic skin grafts and totally
      inhibits T-cell proliferation in LFA-1-deficient mice.
AB  - BACKGROUND: It was recently shown that some strains of mice are capable of
      rejecting transplants independently of B7 and CD40L signaling and that this
      rejection is mediated by CD8(+) T cells. LFA-1 is known to be important for
      CD8(+) T cell activation and cytotoxicity. Therefore, blockade of LFA-1 could be
      important in overcoming costimulation blockade, CD8(+) T-cell-mediated, resistant
      rejection. The purpose of this study was to define the effect of combined
      blockade of the LFA-1 and B7 costimulation pathways on the alloimmune response in
      mice. METHODS: Allogeneic skin transplantation was performed using BALB/c mice as
      donors and C57BL/6J wild-type or LFA-1-deficient (CD11a(-/-)) mice as recipients.
      CTLA4Ig or anti-LFA-1 was administered either as an induction or a prolonged
      therapy. Mixed lymphocyte reactions were conducted to study the effect of CTLA4Ig
      on T-cell proliferation in CD11a(-/-) mice. RESULTS AND CONCLUSIONS:
      Administration of CTLA4Ig completely inhibits CD11a(-/-) T-cell proliferation in
      response to alloantigens and significantly improved skin allograft survival in
      CD11a(-/-) mice. Prolonged treatment of wild-type recipient mice with CTLA4Ig and
      anti-LFA-1 increased median survival time to 45.5 days compared with 16 days
      after induction therapy, but it was not sufficient to induce indefinite allograft
      survival in this model.

PMID- 11821747
TI  - No recurrence of posttransplantation Kaposi's sarcoma three years after renal
      retransplantation.
AB  - Kaposi's sarcoma (KS) develops in 0.5-5% of organ transplant patients; it usually
      regresses upon treatment reduction, but this may result in graft loss
      necessitating return to dialysis and/or retransplantation. Until now
      posttransplantation KS is considered to recur upon reintroduction of
      immunosuppressive treatment, a fact that has limited retransplantation of
      patients with previous KS. We report a patient with posttransplantation KS who
      received a second renal transplantation after having been off immunosuppressive
      treatment for 10 years, in whom KS has not recurred more than 3 years after
      retransplantation. This unique observation suggests that retransplantation of
      patients with previous posttransplantation KS is possible.

PMID- 11821748
TI  - Visceral Leishmaniasis in renal transplant recipients: is it still a challenge to
      the nephrologist?
AB  - A case of visceral Leishmaniasis in a renal transplant recipient is reported
      because of its peculiar clinical presentation: the presence of most clinical
      signs of the disease, such as high-grade fever, marked leucopenia, and
      splenomegaly, but persistent negativity of serology and of bone marrow smear.
      Forty days after the first bone marrow biopsy, the diagnosis was made possible by
      a second biopsy, and the treatment was started with antimonial compounds, which
      led to complete remission of symptoms. A relapse was observed 1 month after
      discontinuation of therapy, successfully treated with a new cycle of the same
      drug and allopurinol. The diagnosis of Leishmaniasis must always be considered in
      immunosuppressed transplant recipients with fever and leucopenia of unknown
      origin, even when serology and bone marrow smear are negative.

PMID- 11821749
TI  - A systematic examination of estimates of cyclosporine area under the curve in
      renal transplant recipients.

PMID- 11821750
TI  - Effects of lansoprazole and rabeprazole on tacrolimus blood concentration: case
      of a renal transplant recipient with CYP2C19 gene mutation.

PMID- 11821751
TI  - MIC expression in renal and pancreatic allografts.
AB  - BACKGROUND: MHC class I chain-related antigen A (MICA) and MHC class I chain
      related antigen B (MICB) are HLA class I related products of polymorphic MHC
      genes. Constitutive expression in normal tissue is limited to gut epithelium but
      can be induced in other epithelial cells by stress. Specific antibodies against
      MICA have been reported in the serum of patients who had rejected kidney
      allografts, suggesting a potential role for these molecules in transplant
      immunopathology. However, expression of MICA and MICB in transplanted organs has
      not been demonstrated. In this study, we report the expression of MICA and MICB
      in renal and pancreatic allograft biopsies, which were obtained due to clinical
      signs of rejection. METHODS: A monoclonal antibody directed against MICA and MICB
      was used to perform indirect immunohistochemistry on formalin fixed, paraffin
      embedded needle biopsies of kidney and pancreas allografts. The results of
      staining were then compared to the standard light microscopic evaluation of the
      biopsies for rejection. RESULTS: A total of 53 individual renal transplant
      biopsies and 19 pancreas transplant biopsies were assayed for expression of MIC.
      Histologically, renal biopsies were diagnosed as no rejection, acute tubular
      necrosis (ATN), acute rejection (AR), chronic rejection (CR), and acute and
      chronic rejection (ACR). No staining was observed in 7 of 10 kidneys showing no
      rejection. All 11 of the kidney biopsies with AR were positive, as were the 11
      ATN cases, 9 of the 11 kidney biopsies with CR, and 7 of the 10 with ACR. The
      acini of normal, nontransplanted, pancreas, control specimen were consistently
      negative; however, islets were positive in all specimens. The acini and islets of
      five histologically normal pancreas biopsies were positive, as were the four
      biopsies with AR, seven biopsies with CR, and two with ACR. CONCLUSIONS: MICA and
      MICB are expressed in epithelial cells in allografted kidney and pancreas that
      show histologic evidence of rejection and/or cellular injury. In addition to
      previous findings of alloantibodies against MICA, expression of these gene
      products may play a role in allograft rejection.

PMID- 11821752
TI  - Successful outcome of acute graft-versus-host disease in a liver allograft
      recipient by withdrawal of immunosuppression.
AB  - BACKGROUND: Graft-versus-host disease (GVHD) after liver transplantation is
      uncommon, and the outcome is almost always fatal. Since 1987, about 30 cases have
      been described, and patient survival is mostly exceptional. METHODS: A 29-year
      old man underwent retransplantation due to chronic cholestatic syndrome, 5 years
      after his first liver transplantation. Indication for the first liver
      transplantation was acute liver failure caused by exsiccosis. After the second
      transplantation, the patient had an initially uneventful course, developing
      thrombocytopenia at day 21 followed by skin rash and septic complications.
      Diagnosis of acute GVHD was made by using serological techniques for HLA-A and
      HLA-DRB and subsequently by fluorogenic sequence-specific primed polymerase chain
      reaction. In addition, donor lymphocytes were marked by immunohistochemical
      methods via biopsies of the skin. Immunosuppressive therapy was withdrawn to
      allow the patient's own immune system to eliminate donor cells. RESULTS: By
      withdrawing the immunosuppressive therapy, clinical and morphological signs of
      GVHD vanished. The patient is doing well without recurrence 13 months after
      transplantation. CONCLUSION: Withdrawal of immunosuppressive therapy is a
      promising approach in the treatment of acute GVHD to allow the patient's immune
      system to reconstitute itself, reject offending lymphocytes, and avoid lethal
      septic complications.

PMID- 11821753
TI  - What role for FTY720, a novel immunosuppressive agent, in canine nonmyeloablative
      hematopoietic stem cell transplantation?
AB  - BACKGROUND: Stable mixed donor/host hematopoietic chimerism was almost uniformly
      achieved in dogs given 200 cGy total body irradiation (TBI) before, and a short
      course of immunosuppression after, transplantation of marrow from dog leukocyte
      antigen-identical littermates, but was transient when the TBI dose was decreased
      to 100 cGy. Here, we examined whether stable engraftment could be achieved in
      five dogs given FTY720 (days -5 and -4), followed by 100 cGy TBI, dog leukocyte
      antigen-identical marrow grafts, and mycophenolate mofetil/cyclosporine. RESULTS
      AND CONCLUSIONS: Although all five dogs showed initial engraftment, four dogs
      rejected their grafts within 11 weeks, whereas one dog was euthanized on day 17
      due to enteritis. This was not different from the control dogs not given FTY720
      (P=0.32). Thus, FTY720 failed to enhance allogeneic engraftment in this model,
      perhaps due to in vivo T-cell depletion of the graft resulting from sequestration
      of donor lymphocytes in host central lymphoid tissues.

PMID- 11821754
TI  - T-cell activation response to allogeneic CMV-infected endothelial cells is not
      prevented by ganciclovir or foscarnet: implications for transplant vascular
      sclerosis.
AB  - BACKGROUND: Cytomegalovirus (CMV), a common infectious complication in transplant
      recipients, has been implicated as an exacerbating agent in the development of
      transplant vascular sclerosis (TVS); however, mechanisms defining this role
      remain to be fully resolved. Our previous studies suggest that CMV-infected graft
      endothelial cells (EC) can initiate a host T-cell activation cascade, and that
      cytokines produced as a consequence enhance graft endothelial alloimmunogenicity.
      Because antiviral therapy has not uniformly attenuated CMV-associated risk of TVS
      development, we have tested the hypothesis that antiviral agents do not affect T
      cell activation by allogeneic CMV-infected EC. METHODS: Human umbilical vein EC,
      inoculated with CMV VHL/E and incubated in the presence or absence of ganciclovir
      (GCV) or foscarnet (PFA), were cocultured with CMV-seropositive or -seronegative
      donor-derived T cells in the presence of these agents, then labeled with
      [(3)H]thymidine. Cocultures were harvested, and radiolabel incorporation was
      assayed by scintillation counting. RESULTS: Limiting dilution analysis
      demonstrated that proliferation frequencies of CMV-seropositive donor-derived T
      cells in response to CMV-infected EC (approximately 80 cells/106, compared with
      approximately 4 cells/10(6) in response to uninfected EC) were not significantly
      modified by GCV (approximately 86 cells/10(6)) or PFA (approximately 82
      cells/10(6)). Likewise, T-cell proliferation curves generated in response to
      stimulator cell titrations were essentially identical regardless of drug
      treatment. CONCLUSIONS: Results of these experiments suggest that although these
      drugs limit CMV replication and dissemination, they do not attenuate the
      inflammatory potential of infected EC, a force that may be a major factor in CMV
      mediated exacerbation of the development of TVS.

PMID- 11821755
TI  - Rapamycin increases transforming growth factor-beta mRNA expression in
      immortalized rat proximal renal tubular cells.

PMID- 11821756
TI  - Simultaneous islet liver allotransplantation in rats.

PMID- 11821757
TI  - Appearance and morality: ethics and otolaryngology-head and neck surgery.

PMID- 11821758
TI  - Anthrax: ENT manifestations and current concepts.
AB  - In light of recent events, anthrax has once again taken center stage in the world
      of science and the world in which we live. Because patients with anthrax may
      initially present to otolaryngology clinics, it is important for the
      otolaryngologist to know how to diagnose and treat this entity. This article will
      present current information on epidemiology, microbiology, pathogenesis/clinical
      manifestations, diagnosis, and treatment with a particular interest in the head
      and neck region.

PMID- 11821759
TI  - Eustachian tube dysfunction after tobacco smoke exposure.
AB  - OBJECTIVE: To examine the effects of tobacco smoke exposure on eustachian tube
      (ET) function. STUDY DESIGN: ET pressures of Sprague Dawley Rats (n = 16) were
      measured after 1, 7, and 15 exposures and in control animals. Passive opening
      pressure, passive closing pressure, active clearance of positive pressure, and
      active clearance of negative pressure were measured. Mucociliary clearance times
      were also quantified (n = 32). RESULTS: Passive opening and passive closing
      pressures of smoke-exposed animals were greater than controls (P < 0.05). Passive
      opening pressure in smoke-exposed animals increased with increasing exposure (P <
      0.001). Animals with 1 exposure had an active clearance of positive pressure
      higher than controls (P = 0.005) and those with 7 and 15 exposures had more
      negative active clearance of negative pressure than controls (P = 0.002, 0.03)
      Mucociliary clearance time was significantly elevated in experimental animals
      with 7 exposures (P = 0.006). CONCLUSIONS: Alterations in ET function exist in
      animals exposed to tobacco smoke. SIGNIFICANCE: ET dysfunction after tobacco
      smoke exposure may predispose children to the development of otitis media.

PMID- 11821760
TI  - The learning curve revisited: stapedotomy.
AB  - OBJECTIVE: To determine whether the outcome of stapedotomy changes with
      experience. STUDY DESIGN AND SETTING: Retrospective case review of an academic
      otologic practice of a fellowship-trained otologist that consisted of 50
      consecutive patients who underwent primary stapedotomy. The main outcome measures
      were preoperative and postoperative audiograms for both the operated ear and the
      opposite ear (control). RESULTS: There were no major complications or loss of
      hearing among the 50 patients. Minor complications included 1 middle ear
      infection, 2 torn flaps, and 1 tympanic membrane perforation. One patient had
      worse conductive hearing loss after surgery. The hearing of 2 patients was
      unchanged. Hearing for the entire group improved (P > 0.001) from a speech
      reception threshold of 55 dB (SD, 17 dB) to 30 dB (SD, 19 dB). Complete closure
      of the air-bone gap was achieved in 20% of the first 10 patients and 30% of the
      last 10 patients. CONCLUSIONS: The results of stapedotomy improve with
      experience, although the learning curve seems less steep than has been reported
      for total or near-total footplate removal. SIGNIFICANCE: Stapedotomy can be
      successfully performed early in surgical experience, but the learning curve
      should be acknowledged and discussed with the patient.

PMID- 11821761
TI  - Bell's palsy in pregnancy: a study of recovery outcomes.
AB  - OBJECTIVE: To study facial nerve recovery in patients with Bell's palsy of
      pregnancy compared with that of the nonpregnant population. METHODS: A
      retrospective chart analysis was conducted of all patients seen within 6 weeks of
      the onset of Bell's palsy of pregnancy, with a minimum of 1-year follow-up.
      Recovery outcomes were compared with similarly chosen randomly selected groups of
      nonpregnant females 15 to 40 years old (group 1), nonpregnant females of all ages
      (group 2), males 15 to 40 years old (group 3), and males of all ages (group 4),
      all of whom were also seen within 6 weeks of onset. Recovery was categorized as
      satisfactory (House-Brackmann grade I to II) or unsatisfactory (House-Brackmann
      grade III or IV). The 2-tailed Fisher exact test was used to statistically
      analyze differences between groups. RESULTS: Fifty-two percent of women with
      Bell's palsy of pregnancy whose facial palsy progressed to complete paralysis
      within 10 days of onset recovered to a satisfactory level compared with 77% to
      88% of comparison patients. These differences were statistically significant in
      all cases. Recovery for those with an incomplete palsy was satisfactory in
      virtually 100% of all patients studied. CONCLUSION: The prognosis for a
      satisfactory recovery for women who develop a complete facial paralysis with
      Bell's palsy while pregnant is significantly worse than for that for the general
      population. This information should be taken into consideration by all physicians
      involved in the counseling of these patients.

PMID- 11821762
TI  - Intratympanic gentamicin therapy for persistent vertigo after endolymphatic sac
      surgery.
AB  - OBJECTIVES: To evaluate the role of intratympanic gentamycin therapy (ITGM) in
      controlling vertigo in patients with refractory Meniere's who have recurrent or
      persistent vertigo after endolymphatic sac surgery. STUDY DESIGN AND SETTING: A
      retrospective review of 491 patients seen in a university balance clinic between
      July 1999 and July 2000. Of these, 68 patients had Meniere's disease; 4 patients
      had recurrent vertigo after endolymphatic sac surgery and were followed for at
      least 1 year. These 4 patients received a series of ITGM injections. Outcome
      measures included control of vertigo and audiometric results. RESULTS: Three of 4
      (75%) patients had control of their vertigo with ITGM therapy. The 1 patient who
      failed ITGM therapy underwent a successful vestibular neurectomy with ultimate
      control of his vertigo. No patients had progression of their sensorineural
      hearing loss. CONCLUSION: ITGM therapy can be used to control vertigo in selected
      patients with Meniere's disease who have persistent vertigo after unsuccessful
      endolymphatic sac surgery. SIGNIFICANCE: ITGM therapy may reduce the need for
      vestibular neurectomy in patients with refractory Meniere's disease after
      endolymphatic sac surgery.

PMID- 11821763
TI  - Congenital middle ear cholesteatomas in children: our experience in 34 cases.
AB  - OBJECTIVES: To evaluate clinical data, extensions, residual disease rate, and
      functional results in cases of congenital cholesteatoma in pediatric patients
      compared with cases of acquired forms. STUDY DESIGN AND SETTING: In a
      retrospective study conducted at a single tertiary care center over a decade, 34
      congenital cholesteatomas (mean patient age, 6.6 years) isolated from a series of
      215 cholesteatomas in children were treated surgically and followed up for an
      average of 83 months. Surgical treatment consisted of the closed technique (CT),
      open technique tympanoplasty in CT [TOT], radical mastoidectomy (RM), or Rambo's
      technique. The main outcome measures were surgical findings, residual lesion
      rate, and hearing assessment. RESULTS: The first surgical procedure was CT in
      85.3%, TOT in 8.8%, RM in 2.9%, and Rambo's technique in 2.9% of patients. Two,
      3, and 4 operations were necessary in 76.5%, 11.4%, and 11.4% of children,
      respectively. Residual lesions were observed in 34.6% of those multi-operated
      patients (7 CT and 2 TOT), 24.1% in those treated with CT, and 29.2% in those
      treated with CT with a planned second look. Mean postoperative pure tone average
      and air-bone gap were 26 and 21 dB, respectively. A speech reception threshold of
      less than 30 dB HL was achieved in 66% of patients. A total of 26
      ossiculoplasties had to be performed (8 partial and 18 total); the mean
      postoperative air-bone gap was lower after the former (15 dB) than after the
      latter (22 dB). A high-frequency pure-tone hearing loss of more than 10 dB was
      uncommon (5.8%). Unsurprisingly, the residual lesion rate seems to be higher for
      congenital than for acquired cholesteatomas, but hearing results are
      significantly better. CONCLUSION: In most cases, staged CT appears to be the best
      technique to treat these lesions, which often develop in a well-pneumatized
      mastoid.

PMID- 11821764
TI  - Psychometric and clinimetric validity of the 20-Item Sino-Nasal Outcome Test
      (SNOT-20).
AB  - A valid measure of rhinosinusitis health status and quality of life is required
      for the complete assessment of treatment effectiveness. The purpose of this study
      was to analyze the psychometric and clinimetric validity of the 20-Item Sino
      Nasal Outcome Test (SNOT-20), a disease-specific, health-related quality-of-life
      measure for rhinosinusitis. The SNOT-20 is a modification of the 31-Item
      Rhinosinusitis Outcome Measure, and it contains 20 nose, sinus, and general
      items. To complete the instrument, patients indicate how much they are affected
      in each area and identify the 5 most important items. The SNOT-20 was completed
      by 102, 72, and 46 patients at the initial visit and at 6 months and 1 year after
      treatment commencement, respectively. Cronbach's alpha was 0.9; test-retest
      scores were highly correlated (r = 0.9). Patients who were more affected had
      greater SNOT-20 scores (P < 0.002), and patients who had improved had greater
      change scores (P < 0.04). Items identified as important had greater scores (P <
      0.0001) and showed greater change scores (P < 0.0002). The SNOT-20 is a valid
      outcome measure for patients with rhinosinusitis; it describes the health burden
      and is sensitive to clinical change.

PMID- 11821765
TI  - Rhinolithiasis: a forgotten entity.
AB  - OBJECTIVE: To review the clinical presentation of patients with rhinoliths, which
      are calcareous concretions with an unclear pathogenesis. STUDY DESIGN AND
      SETTING: Using retrospective chart review we analyzed clinical, radiological, and
      demographic data as well as our diagnostic work-up and management of 8 patients.
      RESULTS: Most patients presented with nonspecific nasal complaints; most
      commonly, purulent rhinorrhea and nasal obstruction. The rhinolith was discovered
      incidentally in some patients. CONCLUSION: Rhinoliths are rare and can have
      various clinical presentations. The treatment of choice is surgical removal.
      SIGNIFICANCE: A high index of suspicion is required for the diagnosis of such a
      forgotten entity.

PMID- 11821766
TI  - Biomechanical properties of tissue-engineered cartilage from human and rabbit
      chondrocytes.
AB  - OBJECTIVE: To describe tissue-engineered cartilage from rabbit and human
      chondrocytes. STUDY DESIGN AND SETTING: Chondrocytes from rabbit and human ears
      were seeded onto a template and implanted for 8 or 16 weeks of in vivo
      incubation. RESULTS: For the 8-week and 16-week groups, the UTS for cartilage was
      3.8 MPa and 3.7 MPa, stiffness was 62.4 MPa and 51.8 MPa, and resilience was
      181.8 J/m(3) and 109.1 J/m(3), respectively. Experimental cartilage was
      significantly different from controls. From 5 human specimens, the UTS was 5.4
      MPa, stiffness was 6.6 MPa, and resilience was 2.0 J/m(3). The control had UTS of
      8.8 MPa, stiffness of 12.2 MPa, and resilience of 2.9 J/m(3). Histology showed
      mature cartilage but with a fibrovascular infiltrate and increased cellularity.
      CONCLUSIONS: Mechanical properties of tissue-engineered cartilage can be
      quantified and are less than that of controls.

PMID- 11821767
TI  - Tracheal stenosis after percutaneous dilational tracheotomy.
AB  - OBJECTIVE: In many critical care units percutaneous dilational tracheotomy (PDT)
      has become an alternative to open tracheotomy. Although significant tracheal
      stenosis after PDT has been reported, the exact incidence is unknown. We report
      our findings on endoscopic laryngotracheoscopy for a group of patients who had
      undergone PDT more than 6 months before their examination. STUDY DESIGN AND
      SETTING: We did a retrospective review of 108 trauma patients who underwent PDT
      at least 6 months before enrollment in the study. Twenty-eight patients were
      either deceased or ineligible. Participation requests were mailed to the last
      recorded address of 80 patients. Thirty-four of those patients were contacted by
      phone, and 14 indicated their willingness to participate. Only 10 patients were
      able to make it to the clinic for examination. After transorally anesthetizing
      the hypopharynx and larynx with 4% lidocaine, each patient underwent flexible
      laryngotracheoscopy. Findings were categorized as normal or tracheal stenosis
      (<25%, 25% to 50%, or >50%). RESULTS: The tracheotomy site was virtually
      undetectable in 5 patients. In 4 patients, a scar was visible at the tracheotomy
      site, but there was no decrease in cross-sectional area. In 1 patient there was a
      25% to 50% stenosis. All patients were completely asymptomatic with regard to
      airway and voice quality. CONCLUSION: One out of 10 patients in our series had a
      significant but asymptomatic stenosis after PDT. The risk of tracheal stenosis in
      PDT appears to be the same as that of open tracheotomy.

PMID- 11821768
TI  - Stomal recurrence after total laryngectomy for squamous cell carcinoma of the
      larynx.
AB  - OBJECTIVE: Stomal recurrence after total laryngectomy is one of the most serious
      issues in the management of laryngeal carcinoma. The management of stomal
      recurrence, including chemotherapy, radiotherapy, and surgery, has been reported
      as unsatisfactory. STUDY DESIGN AND SETTING: From 1985 to 1995, 69 patients
      underwent total laryngectomy for the treatment of laryngeal cancer at the
      University of Tokyo Hospital. To identify the risk factors for stomal recurrence,
      we analyzed these patients according to various clinicopathological factors.
      RESULTS: Stomal recurrence developed in 6 of 69 patients who underwent total
      laryngectomy for laryngeal carcinoma. Statistical analysis reveals that primary
      site, preoperative tracheotomy, and paratracheal lymph node metastasis are
      significant risk factors for stomal recurrence. CONCLUSION: Intensive follow-up
      should be performed for patients with glottic carcinoma who had preoperative
      tracheotomy, paratracheal lymph node metastasis, or both to detect stomal
      recurrence at an early stage.

PMID- 11821769
TI  - Radiofrequency versus LAUP for the treatment of snoring.
AB  - OBJECTIVE: To compare efficacy and tolerance of controlled temperature
      radiofrequency and laser-assisted uvulopalatopharyngoplasty (LAUP) for the
      treatment of snoring. METHODS: This was a prospective, nonrandomized study on 30
      patients who snored. All patients had a sleep night study. Only patients with
      simple snoring or mild sleep apnea and soft palate obstruction were included.
      Efficacy was subjectively evaluated by the bed partner 2 months after the last
      treatment. Tolerance was estimated daily by the patient during 18 first
      postoperative days. Discomfort, pain, medication intake, diet, and number of days
      off from work were assessed. RESULTS: Both treatments were effective on snoring.
      Mean discomfort and pain as well as mean intake of analgesics were significantly
      greater with laser-assisted uvulopalatopharyngoplasty. CONCLUSION: Controlled
      temperature radiofrequency was as effective as laser-assisted
      uvulopalatopharyngoplasty on snoring on a short-term basis but was better
      tolerated.

PMID- 11821770
TI  - Hemangioma of the external auditory canal.

PMID- 11821771
TI  - Skull base fungal osteomyelitis in an immunocompetent host.

PMID- 11821772
TI  - Primary tracheal papillomatosis presenting as reactive airway disease.

PMID- 11821773
TI  - Osteosarcoma of the hyoid bone.

PMID- 11821774
TI  - Recurrent epithelial-myoepithelial carcinoma of the parotid with direct
      intracranial extension.

PMID- 11821775
TI  - Angiocentric T-cell lymphoma of the temporal bone.

PMID- 11821776
TI  - The intubating laryngeal mask.

PMID- 11821777
TI  - Vertebral hydatid disease presenting as a parapharyngeal and neck mass: a case
      report.

PMID- 11821779
TI  - Effects of terrorism on otolaryngology: a work in progress.

PMID- 11821778
TI  - The association between periodontal disease and peritonsillar infection: a
      prospective study.
AB  - OBJECTIVE: To study the relationship between periodontal status and peritonsillar
      disease/recurrent tonsillitis. STUDY DESIGN AND SETTING: A total of 158 patients
      presenting over a 3-year period with peritonsillar abscess (PTA) confirmed by
      needle aspiration and a control group of 112 patients booked for elective
      tonsillectomy for recurrent tonsillitis (RT) were examined in terms of their
      periodontal status using the WHO Community Periodontal Index of Treatment Needs
      (CPITN). RESULTS: The mean CPITN index was 2.81 (Standard Deviation [SD], 1.10)
      in patients with PTA and 1.41 (SD, 0.92) in patients with RT. One hundred seven
      of 158 patients with PTA had significant periodontal pathology (CPITN, 3 or 4)
      compared with 12 of 112 patients with RT. These differences were statistically
      significant. CONCLUSION: Patients with peritonsillar abscess had an increased
      prevalence of periodontal disease as compared with patients with recurrent
      tonsillitis. SIGNIFICANCE: There is a need to further explore this correlation
      and determine its nature, although it could be the result of common pathogenic
      factors, a causal relation cannot be excluded.

PMID- 11821780
TI  - Risk factors for esophageal cancer and the multiple occurrence of carcinoma in
      the upper aerodigestive tract.
AB  - The multiple occurrence of squamous cell carcinoma is frequent in the upper
      aerodigestive tract (UADT). Risk factors not only for esophageal cancer, but also
      for multiple cancer in the UADT, were reviewed. Both cigarettes smoking and
      alcohol drinking are will known risk factors for esophageal cancer. The joint
      effect of these 2 factors on the occurrence of esophageal cancer is considered to
      be synergetic, but familial aggregation of esophageal cancer is also reported.
      Regarding the multiple occurrence of cancer of the UADT, both heavy smoking and
      heavy drinking play an important role. In addition, our studies revealed that a
      family history of UADT cancer might also be a risk factor for multiple cancer.
      Recent improvement of molecular biology techniques have helped to show that tumor
      suppressor genes, such as p53 and FHIT, may be candidates for target genes of
      these risk factors.

PMID- 11821781
TI  - The relation of alcohol consumption and cigarette smoking to the multiple
      occurrence of esophageal dysplasia and squamous cell carcinoma.
AB  - BACKGROUND: The unique pathologic features of esophageal tumors in patients with
      esophageal cancer includes the presence of multiple occurrence within the
      esophagus. The aim of this study is to clarify the molecular mechanism of
      carcinogenesis of multiple esophageal squamous cell carcinomas in the Japanese.
      METHODS: We studied the relationship between the incidence of patients with
      multiple carcinomas and the coexistence of dysplasia lesions with p53 protein
      accumulation, alcohol consumption, and cigarette smoking. Among 76 cancer lesions
      and 60 cases of dysplasia, p53 accumulation was studied by means of
      immunohistochemical analysis. RESULTS: The incidence of patients with multiple
      carcinomas in the high-risk group was 33%, and the incidence of patients with a
      coexistence of dysplasia in the high-risk group was 67%. The incidence of
      patients with multiple carcinomas or the coexistence of dysplasia in the high
      risk group was much higher than that of the middle-risk and low-risk groups (P
      <.0001 and P =.04, respectively). The average number of abnormal epitheliums,
      such as cancer and dysplasia, in the high-risk group was 3.2 +/- 2.1. The average
      number of abnormal epitheliums was much higher than that of the other groups (P
      =.02). For carcinoma lesions, the incidence of lesions with a positive p53
      protein accumulation in the high-risk group was 91%. Regarding dysplasia lesions,
      the incidence of lesions with a positive p53 protein accumulation in the high
      risk group was 80%. The incidence of both cancer and dysplasia lesions with a
      positive p53 protein accumulation in the high-risk group was higher than that of
      the other groups. CONCLUSIONS: The pattern of p53 accumulation in dysplasia in
      the high-risk group was closely similar to that in cancer of the high-risk group.
      These findings support the concept of field carcinogenesis of the esophagus.

PMID- 11821782
TI  - The subepithelial extension of esophageal carcinoma for determining the resection
      margin during esophagectomy: a serial histopathologic investigation.
AB  - BACKGROUND: An evaluation of the safe resection margin in esophagectomy or
      esophageal endoscopic mucosal resection for carcinoma, based on serial histologic
      investigations by measuring the length of subepithelial extension of the lesion
      beneath the noncancerous epithelium, has not been reported. METHODS: Forty-eight
      patients with esophageal carcinoma restricted to within the esophageal wall
      including 67 lesions (27 mucosal, 27 submucosal cancer, and 13 lesions of cancer
      invading to proper muscular layer) were histopathologically examined. The length
      of subepithelial extension (SEE) beneath the noncancerous epithelium of each
      lesion was measured and the clinicopathologic significance of SEE was discussed.
      RESULTS: Among these 67 lesions in 48 cases, there were 17 (25.4%) lesions with
      SEE. The rates of coexistence of SEE were 3.7, 37.0, and 46.2% in mucosal and
      submucosal cancer, and cancer invading the proper muscular layer, respectively.
      When the positive rate was more than 50% for the factors of SEE--lymphatic
      permeation, blood vessel permeation, and intramural metastasis--the prognosis was
      significantly poorer in the patients with esophageal cancer. CONCLUSIONS: When
      the lesion was restricted to within the mucosal layer, SEE was almost negligible
      at resection. The coexistence of SEE was thus found to be one of the prognostic
      factors predicting a poor prognosis.

PMID- 11821783
TI  - Biologic and clinical significance of squamous epithelial dysplasia of the
      esophagus.
AB  - Squamous epithelial dysplasia is frequently encountered in the cancerous
      esophagus. However, its biological and clinical significance have not yet been
      fully elucidated. Investigations in squamous cell dysplasia of the esophagus have
      been performed to date in our department. We consider dysplasia to be the
      earliest malignancy of the esophagus based on such biologic features as the
      histopathologic findings, the proliferative activity, and the altered expression
      of cancer-associated genes. It is essential to detect and treat these early
      lesions endoscopically. Hopefully the findings of further studies of dysplasia
      can help to elucidate the mechanism of carcinogenesis in esophageal squamous cell
      carcinoma.

PMID- 11821784
TI  - Surgical and oncological advances in the treatment of esophageal cancer.
AB  - BACKGROUND: Chemoradiotherapy (CR) and hyperthermochemoradiotherapy (HCR) have
      been performed on numerous patients with esophageal cancer. These neoadjuvant
      therapies for esophageal cancer are done widely. The purpose of this study is to
      demonstrate the recent advances in surgical and oncological treatment. METHODS:
      From 1967 to 2000, 847 patients who underwent an esophagectomy were classified
      into 4 groups according to the date of operation. Group 1 consisted of 110
      patients who underwent an esophagectomy in the first 10-year period (1967-1976),
      group 2 consisted of 194 patients who had operations from 1977 to 1986, group 3
      comprised 400 patients who had operations from 1987 to 1996, and group 4
      comprised 143 patients who had operations from 1997 to 2000. From 1967 to 2000,
      322 patients with neoadjuvant therapy and esophagectomy were classified into 6
      groups according to the kinds of anticancer drugs that were administered. Group A
      received regimen A, using BLM (5 mg iv) 6 times as the chemotherapeutic drug in
      the early period (1965-1990); group B received regimen B, using cis
      diaminedichloroplatinum (CDDP) (40 mg/m2) 3 times as the chemotherapeutic drug in
      the second period (1990-1997); and group C received regimen C, using CDDP (40
      mg/m2) and 5FU (250 mg/m2) daily in the most recent period (1997-2000). The HCR
      group was also divided into the following 3 groups: Group D, who received regimen
      A and hyperthermia 6 times in the early period; group E, who received regimen B
      and hyperthermia 6 times in the next period; and group F, who received regimen C
      and hyperthermia 6 times in the most recent period. The local response and the
      long-term results were investigated. RESULTS: A complete removal of the primary
      tumor was achieved in 29%, 39%, 62%, and 68% of the patients in groups 1, 2, 3,
      and 4, respectively. The 30-day operative mortality rates were 11%, 4%, 1%, and
      0% in groups 1, 2, 3, and 4, respectively. The 5-year survival rates for all
      patients in groups 1, 2, and 3 were 16.7%, 19.2%, and 44.4%, respectively. The
      cases in which CR or HCR was evaluated to be effective numbered 44 (48.4%) in
      group A, 22 (73.3%) in group B, 8 (66.7%) in group C, 79 (63.7%) in group D, 36
      (73.5%) in group E, and 12 (75.0%) in group F. Our clinical results thus showed
      CDDP to have a greater effect than BLM, while HCR was shown to have a greater
      effect than CR. CONCLUSIONS: Preoperative therapy, especially using CDDP and
      hyperthermia, has improved thanks to recent advances in the treatment of
      esophageal cancer.

PMID- 11821785
TI  - Preoperative hyperthermochemoradiotherapy for esophageal carcinoma.
AB  - BACKGROUND: In order to acquire an improved prognosis, preoperative hyperthermia
      combined with chemotherapy and radiotherapy (HCR) has been performed in our
      department for patients with esophageal carcinoma. METHODS: The experimental and
      clinical investigations that have been continuously performed in our department
      were introduced with regard to the therapeutic effect brought by HCR for
      carcinoma, chiefly for esophageal carcinoma. RESULTS: A series of our
      investigations have demonstrated the excellent anticancer effect of HCR for
      esophageal carcinoma. CONCLUSIONS: Preoperative HCR has contributed to
      improvements in the prognosis of patients with esophageal carcinoma and is
      expected to make marked progress in the future with further development of
      anticancer agents and improvements in the hyperthermia devices.

PMID- 11821786
TI  - Analysis of the gene-expression profile regarding the progression of human
      gastric carcinoma.
AB  - BACKGROUND: Tumor tissue consists of a variable mixture of tumor and host-cell
      populations. Recent developments in laser microdissection (LMD) and cDNA
      microarray analysis have encouraged us to study the differential gene expression
      profiles among normal cells, primary carcinoma cells, and metastatic carcinoma
      cells in cases of gastric carcinoma. METHODS: Total RNA was extracted from the
      cells obtained by means of LMD from the primary carcinoma, the corresponding
      gastric epithelium, and the lymph node metastasis in 5 cases of primary gastric
      carcinoma. RNA was amplified by the T7-based amplification system to be applied
      to a cDNA microarray. Thereafter, the differentially expressed genes among the 3
      populations were evaluated. RESULTS: cDNA samples for microarray studies were
      successfully obtained from each cell population of 5 cases. The cDNA microarray
      demonstrated that several interesting genes, such as cell-cycle regulators and
      growth factors, were overexpressed in the metastatic cells compared with in the
      primary carcinoma cells. Oncogenes and cell-adhesion molecules were more
      overexpressed in the primary carcinoma cells than in the normal cells. On the
      other hand, caspase 8 and cadherin were more suppressed in the primary carcinoma
      cells than in the normal cells. Interestingly, among the matrix metalloproteinase
      family, only MMP7 was identified as a differentially overexpressed gene in both
      the primary carcinoma and the metastatic cells in comparison with the normal
      cells. CONCLUSIONS: This study demonstrated that the combined use of LMD, T7
      based amplification, and a cDNA microarray enabled us to identify genes directly
      associated with each population of tumor tissue. The method will open up new
      possibilities for the precise gene analysis of tumor progression and metastasis.

PMID- 11821787
TI  - Angiogenesis as a target for gastric cancer.
AB  - BACKGROUND: The growth of solid tumors and the formation of metastases depend on
      angiogenesis. Both tumor cells and host cells secrete a variety of factors to
      stimulate angiogenesis. METHODS: We investigated the expression of angiogenic
      factors in gastric cancer in vitro and in vivo. RESULTS: The expression of one of
      the angiogenic factors, vascular endothelial growth factor antigen, in gastric
      cancer cells can thus serve as a pertinent predictive factor for hematogenous
      invasion or metastasis, in addition to having prognostic value. The presence of
      micrometastasis in bone marrow was closely related to vascular endothelial growth
      factor positivity and microvessel density in the primary gastric cancer. In in
      vivo experiments antiangiogenic agents with cytotoxic anticancer drugs formed a
      highly effective modulator combination for the treatment of the Lewis lung
      carcinoma against primary and metastatic disease. CONCLUSIONS: Antiangiogenic
      agents may thus be valuable for long-term administration to maintain tumor
      dormancy because drug resistance does not develop, and these agents have a
      sustained effect. As a target, antiangiogenic therapy may therefore be
      potentially able to prolong survival time of patients with gastric cancer.

PMID- 11821788
TI  - Microsatellite instability in cancer: what problems remain unanswered?
AB  - Analyses of microsatellite instability have been prevalent, particularly in the
      field of oncology. However, the literature on this subject is diverse. The
      discrepancies may derive from methodological problems in the conventional
      techniques used for analysis. Problems include low quantitativity in the
      detection systems, inaccurate migration in electrophoresis, and Taq polymerase
      mediated modifications of polymerase chain reaction products. Indeed, use of a
      new fluorescent technique where these problems have been overcome has elucidated
      various intriguing and previously unrecognized aspects of microsatellite
      instability in human cancers. Patterns of microsatellite changes observed in
      various human cancers can be classified into 2 subtypes, those showing relatively
      small changes within 6 base pairs (type A) and those exhibiting drastic changes
      over 8 base pairs (type B). Although type A microsatellite instability has been
      connected to defective mismatch repair phenotype, the relationship between type B
      microsatellite instability and defective mismatch repair phenotype remains
      unclear. Nevertheless, as symbolized in cases of hereditary nonpolyposis
      colorectal cancer, connections between type B microsatellite instability and
      familial predisposition have been suggested in some cancers. The molecular
      background of type B microsatellite changes warrants particular attention.

PMID- 11821789
TI  - DNA ploidy and its clinical implications in gastric cancer.
AB  - BACKGROUND: Biological characteristics of gastric cancer depend mostly on genetic
      alterations in the cancer cells of individuals. To precisely predict the
      biological behavior and clinical outcome of individual cancer, it may be
      important to clarify the DNA profiles of cancer cells in each case. METHODS: We
      have reviewed the most important results of studies on DNA ploidy of gastric
      cancer published in the English literature during the last 2 decades. RESULTS:
      Gastric carcinoma with aneuploidy has been shown to have a high proliferative
      activity and a high metastatic or invasive potential, thus leading to a poor
      prognosis as compared to diploid tumors. CONCLUSION: Analyses of DNA ploidy in
      gastric cancer may provide clinically useful information on diagnostic,
      therapeutic, and prognostic aspects. Further investigations may be needed to
      clarify the relationship between chromosome instability and DNA ploidy.

PMID- 11821790
TI  - The biologic features of intramucosal gastric carcinoma with lymph node
      metastasis.
AB  - This review concentrates on the clinicopathologic studies and molecular biologic
      studies of intramucosal gastric carcinomas (IMGCs) with lymph node metastasis
      that have been published to date. There have been several reports in which IMGCs
      with lymph node metastasis were compared with IMGCs without lymph node metastasis
      from the view of clinicopathologic features. However, there have been a few
      reports in which IMGCs with lymph node metastasis were compared with IMGCs
      without lymph node metastasis from the view of molecular biologic features. In
      general, IMGCs with lymph node metastasis have been commonly reported to be large
      lesions, poorly differentiated adenocarcinoma, and associated with peptic ulcer,
      in comparison with IMGCs without lymph node metastasis. Regarding genetic studies
      or molecular biologic studies, only DNA distribution pattern, proliferative cell
      nuclear antigen and the monoclonal antibody Ki-67, or matrix metalloproteinases 2
      and 9 have been investigated in IMGCs with lymph node metastasis. The malignant
      potential of the carcinoma cells cannot been evaluated by a clinicopathologic
      study with the use of hematoxylin and eosin staining. It may be unavoidable that
      minimal operation is widely accepted for the treatment of IMGCs. It may be more
      essential to establish the staging by both clinicopathologic and molecular
      biologic examinations to rule out the presence of IMGCs with lymph node
      metastasis.

PMID- 11821791
TI  - Clinical application of hyperthermia combined with anticancer drugs for the
      treatment of solid tumors.
AB  - BACKGROUND: Hyperthermia is one of the modalities used to treat various forms of
      malignancies, including esophageal, stomach, or rectal cancers. METHODS: The
      basic mechanism of synergism between hyperthermia and anticancer drugs, as well
      as the clinical result of hyperthermia for the treatment of gastrointestinal
      malignancy, was reviewed. RESULTS: Hyperthermia exerts a cytotoxic effect in
      combination with various mechanisms. Hyperthermia is applied in combination with
      chemotherapy and/or radiotherapy in the clinical setting. Among the anticancer
      drugs that are synergistic with hyperthermia is cisplatin, which is prevalent for
      clinical application. The mechanism of enhanced cytotoxicity of cisplatin
      includes increased intracellular drug accumulation, increased platinum-DNA
      adducts, and inhibition of DNA repair. At our institute,
      hyperthermochemoradiotherapy was conducted as a neoadjuvant therapy for either
      operative cases or as a palliative therapy for unresectable cases for esophageal
      and rectal cancers. In both situations, hyperthermochemoradiotherapy showed an
      excellent benefit in both the control of local recurrence and and in an
      improvement in patient survival. Regarding gastric cancer, the most popular
      application of hyperthermia was the intraoperative hyperthermic peritoneal lavage
      with cisplatin. This treatment modality demonstrated a better control of the
      disseminated lesion. Regarding the factors that influence thermosensitivity, in
      vitro experiments demonstrated the heat-shock proteins or tumor suppressor gene
      p53 to be related to thermosensitivity. In the clinical setting, these factors
      remain to be firmly established as predictive factors for thermosensitivity.
      CONCLUSIONS: It is evident that hyperthermia was effective in the control of far
      advanced gastrointestinal malignancies. When more reliable factors for the
      prediction of the treatment response can be established, the standard guidelines
      for the application of hyperthermia can then be made.

PMID- 11821792
TI  - Therapeutic value of lymph node dissection and the clinical outcome for patients
      with gastric cancer.
AB  - BACKGROUND: While the incidence of gastric cancer differs greatly between Japan
      and other countries, both diagnostic and treatment modalities for patients with
      gastric cancer have improved in Japan. What follows is an overview of the effects
      of lymph node dissection for such patients. METHODS: We analyzed data on 2152
      Japanese men and women with gastric cancer who underwent surgical resection from
      1965 to 1995 at Kyushu University in Fukuoka, Japan. We focused on time trends of
      surgical management, including lymph node dissection and postoperative outcome.
      RESULTS: In all cases of gastric cancer, the rate of early gastric cancer
      increased from 18% in the first 6-year period to 57% in the last 5-year period.
      Extensive lymph node dissections (D2 and D3) were performed more frequently in
      recent years. Due to early identification of the cancer and upgraded
      perioperative care, both postoperative morbidity and mortality rates 30 days
      after surgery have decreased greatly, even in aged patients. CONCLUSIONS: Early
      tumor detection, standardized surgical treatment, including routine lymph node
      dissection, and improved perioperative management have led to increased survival
      time among patients with this malignancy.

PMID- 11821793
TI  - Assessment of the intestinal permeability after a gastrectomy and the oral
      administration of anticancer drugs in rats: nitric oxide release in response to
      gut injury.
AB  - BACKGROUND: Although intestinal permeability is known to increase in conditions
      of stress (such as endotoxemia, septic shock, and ischemia-reperfusion), the
      mechanism of gut barrier dysfunction during chemotherapy remains to be
      elucidated. We designed an experiment in which a gastrectomy and anticancer drugs
      were administered to rats to assess the extent of damage or an increase in
      permeability of the intestinal mucosa. METHODS: The rats were separated into the
      following groups: group A, no operation without an anticancer drug (control
      rats); group B, a gastric operation; group C, chemotherapy; and group D, a
      gastric operation followed by chemotherapy. Six rats were placed in each group.
      The groups that were given the anticancer drug received 45 mg/kg for 7 and 14
      days, respectively. Intestinal permeability was determined by an injection of
      fluorescein isothiocyanate-dextran (FITC-D) intravenously and the measurement of
      the amount of FITC-D leakage in the luminal lavage. The plasma nitric oxide
      concentrations were measured spectrophotometrically by the Griess reaction. The
      cell surface expression of CD44 in the rat small intestine was evaluated
      immunohistochemically. RESULTS: During the entire experimental period, the FITC-D
      levels in the anticancer drug that was administrated to rats (groups C and D)
      were significantly higher than the levels in groups A and B (P <.001). Similarly,
      the plasma nitric oxide concentration increased significantly not only in groups
      C and D but also in group B (P <.05). A linear regression analysis revealed a
      positive significant correlation between FITC-D and the plasma nitric oxide
      levels (r = 0.617; P <.001). When the anticancer drug was administered, the
      intestine histologically revealed so-called mucosal atrophy and a decreased
      expression of CD44 within the intestinal mucosa. CONCLUSIONS: The administration
      of anticancer drugs impairs the gut barrier function, possibly by reducing the
      cell-cell and cell-matrix interactions. This may contribute to the development of
      hyperpermeability that is induced by an overexpression of nitric oxide.

PMID- 11821795
TI  - The role of adenoma for colorectal cancer development: differences in the
      distribution of adenoma with low-grade dysplasia, high-grade dysplasia, and
      cancer that invades the submucosa.
AB  - BACKGROUND: The purpose of this study was to elucidate the role of adenoma in the
      early stage of colorectal cancer development, we focused on the clinicopathologic
      relationship between adenoma with low-grade dysplasia (ALGD), adenoma with high
      grade dysplasia (AHGD), and cancer that invades the submucosa in the colorectum.
      METHODS: We clinicopathologically examined a total of 553 adenomas and 58 cancers
      that invaded the submucosa. The tissues were excised from 479 patients who
      underwent total colonoscopy. RESULTS: The percentage of ALGD was 79.9% in the
      proximal colon, 70.5% in the distal colon, and 48.3% in the rectum, respectively.
      The percentages of AHGD and cancer were 14.5% and 5.6% in the proximal colon,
      21.3% and 8.2% in the distal colon, and 35.4% and 16.3% in the rectum,
      respectively. In contrast with the distribution of ALGD, the distribution of both
      AHGD and cancer shifted from the proximal to the distal site, with a statistical
      significance (P <.01). When the distribution of adenoma was compared according to
      tumor size, both large- and small-sized AHGD showed a similar cancer
      distribution, however, both large- and small-sized ALGD showed different
      distributions. CONCLUSION: An important role of AHGD for cancer development in
      the colorectum may relate to the similar distribution between AHGD and cancer;
      however, the different distributions observed between ALGD, AHGD, and cancer
      suggested that ALGD has only a slight association with the development of cancer.

PMID- 11821794
TI  - The administration of hypotonic intraperitoneal cisplatin during operation as a
      treatment for the peritoneal dissemination of gastric cancer.
AB  - BACKGROUND: Gastric cancers with serosal invasion often spread to the peritoneal
      surface. Beneficial effects of hypotonic intraperitoneal cisplatin against
      peritoneal dissemination was noted in experimental models. Prophylactic hypotonic
      intraperitoneal cisplatin during operation should therefore be examined in human
      gastric cancer. METHODS: Isotonic intraperitoneal cisplatin was administered
      immediately after gastrectomy in increasing doses to patients with locally
      advanced gastric cancer until dose-limiting toxicity (DLT) was observed in 2 or
      more of 3 patients who were treated at a specific dose level. The osmolarity
      reduction and dose escalation trial for hypotonic intraperitoneal cisplatin was
      then performed until DLT was observed in 2 or more of 6 patients. RESULTS: The
      dose-escalation trial revealed the DLT of isotonic intraperitoneal cisplatin in
      the form of nausea and vomiting at a dose of 120 mg/m2. Isotonic intraperitoneal
      cisplatin treatment was recommended at a dose of 100 mg/m2. Because of the
      possible enhanced toxicity by hypotonic solution, hypotonic intraperitoneal
      cisplatin at a dose of 70 mg/m2 in one-half normal saline solution was injected,
      but no serious toxic reaction was observed. Hypotonic intraperitoneal cisplatin
      at a dose of 70 mg/m2 that had been dissolved in distilled water was then
      injected. It was accompanied by serious renal toxicity in 2 of 6 patients. Dose
      escalation was thus terminated, and the trial in an additional 25 patients
      confirmed that the toxicity of hypotonic intraperitoneal cisplatin at a dose of
      70 mg/m2 was tolerable. A pharmacokinetic study to determine the maximum
      concentration and the area under the curve of concentration versus time of
      platinum revealed that hypotonic intraperitoneal cisplatin did not appear to
      increase the maximum concentration or area under the curve of the total and free
      platinum in the plasma in comparison with the isotonic intraperitoneal cisplatin
      at the same dose. CONCLUSIONS: Hypotonic intraperitoneal cisplatin treatment with
      distilled water at the time of a gastric resection is well tolerated. Hypotonic
      intraperitoneal cisplatin does not increase the plasma level of platinum at a
      dose of 70 mg/m2. Phase II/III studies are still required to clarify the efficacy
      of hypotonic intraperitoneal cisplatin for the treatment of the peritoneal
      dissemination in gastric cancer.

PMID- 11821796
TI  - Estimation of angiogenesis with anti-CD105 immunostaining in the process of
      colorectal cancer development.
AB  - BACKGROUND: The expression of panendothelial markers (eg, CD34, CD31, and factor
      VIII) is not always observed in angiogenic vessels, and such markers are not
      useful for measuring angiogenesis. In contrast, CD105 is preferentially expressed
      in angiogenic vessels and thus may be valuable for measuring angiogenesis. We
      hypothesized that microvessel quantification by means of CD105 might be useful
      for measuring angiogenesis in the colorectal adenoma-carcinoma sequence. METHODS:
      We immunohistochemically investigated 54 cases of colorectal adenomas and 20
      cases of carcinomas using monoclonal antibodies CD34 and CD105, and microvessel
      density (MVD) was counted at x200 magnification. RESULTS: Microvessels positive
      for CD34 were distributed almost uniformly in adenomas. In contrast, microvessels
      positive for CD105 were preferentially observed in the surface area of adenomas.
      In carcinomas, CD34 stained only a proportion of blood vessels that were positive
      for CD105. No significant difference of MVD for CD34 was observed in the
      colorectal adenoma-carcinoma sequence. In contrast, an increment of MVD for CD105
      from low-grade to high-grade dysplasia (P <.0001) and that from high-grade
      dysplasia to carcinomas (P <.05) was statistically significant. CONCLUSIONS:
      Assessing neovascularization with CD105 in the process of colorectal cancer
      development may thus be a valuable marker for predicting the risk of colorectal
      cancer development.

PMID- 11821797
TI  - The relationship between cyclin B1 overexpression and lymph node metastasis in
      human colorectal cancer.
AB  - BACKGROUND: Although the molecular and biologic changes in G1/S cyclins have been
      well characterized, alterations in G2/M cyclin and its possible roles in cell
      proliferation and metastatic behavior remain to be elucidated. METHODS: The
      cyclin B1 expression immunohistochemically determined in 109 patients with
      colorectal cancer was investigated from the standpoints of tumor invasion, lymph
      node metastasis, and prognosis. These findings were analyzed in relation to the
      growth fractions determined with Ki-67 and proliferating cell nuclear antigen and
      to the expression of p53 protein. RESULTS: A positive cyclin B1 expression was
      found in 62 (56.8%) of 109 patients. Tumors with cyclin B1 overexpression did not
      involve any lymph node, did not permeate the lymphatics, did not invade the blood
      vessels, and tended to be of Dukes' stage B. Those characterized by a lower
      expression of cyclin B1 protein frequently metastasized to the lymph nodes,
      showed lymphatic permeation or vessel invasion, and tended to be of Dukes' stages
      C or D. The overexpression of cyclin B1 showed no significant correlation with
      proliferative activities determined by means of Ki-67 or proliferating cell
      nuclear antigen or with the expression of p53 protein. Although the cyclin B1
      positive group seemed to survive longer in comparison with the cyclin B1-negative
      group, the difference was not statistically significant. In a logistic regression
      analysis the cyclin B1 expression proved to be a significant factor related to
      the occurrence of lymph node metastasis, as did tumor size and curability of
      disease. CONCLUSIONS: These findings suggest a close correlation between a lack
      of cyclin B1 immunostaining and a stronger metastatic behavior in colorectal
      cancer. This inverse relationship was not ascribed to a mere consequence of cell
      proliferation but rather to organ specificity, heterogeneity, or an uncontrolled
      cyclin B1 expression probably caused by the deregulation of G2/M transition.

PMID- 11821798
TI  - Hyperthermia for rectal cancer.
AB  - BACKGROUND: In order to improve the clinical results of rectal cancer,
      hyperthermia has been prescribed in combination with chemotherapy and
      radiotherapy. The techniques of hyperthermia and their clinical applications to
      rectal cancer were reviewed. METHODS: The development of heating devices has been
      intensively investigated, including external heating devices, intraluminal
      heating devices, circulation of warmed saline solution, and whole body
      hyperthermia. RESULTS: Nonrandomized and randomized trials for rectal cancer have
      demonstrated an improved local response with the combined use of hyperthermia and
      conventional treatments. A preoperative therapy with hyperthermia increased
      resectability and decreased local recurrence, resulting in the improvement of the
      postoperative prognosis. There were no major postoperative complications related
      to the preoperative treatment. A lower incidence of local recurrence was observed
      in groups that underwent intra- or postoperative hyperthermia treatment, as
      compared with control groups. In cases with unresectable or local recurrent
      rectal cancer, hyperthermia achieved a local tumor regression and prolonged pain
      relief. CONCLUSIONS: These clinical data suggest that hyperthermia combined with
      radiation or chemotherapy demonstrates great promise for the treatment of
      patients with carcinoma of the rectum.

PMID- 11821799
TI  - Protracted hepatic arterial infusion with low-dose cisplatin plus 5-fluorouracil
      for unresectable liver metastases from colorectal cancer.
AB  - BACKGROUND: Hepatic arterial infusion (HAI) chemotherapy is a treatment option
      for unresectable liver metastases from colorectal cancer, but it is not yet a
      standard treatment. The aims of this study were to demonstrate the efficacy of
      protracted HAI chemotherapy with low-dose cisplatin plus 5-fluorouracil for
      patients with unresectable liver metastases from colorectal cancer. METHODS:
      Twenty-two patients with unresectable liver metastases from colorectal cancer
      were treated with continuous HAI of 300 mg/m2 5-fluorouracil for 5 days a week
      and 6 mg/m2 cisplatin for 2 hours on 5 consecutive days a week. The plasma
      concentrations of cisplatin and 5-fluorouracil during the treatment were measured
      for a pharmacokinetic study. RESULTS: Of the 22 patients, 2 had a complete
      response, 13 had a partial response, 6 had stable disease, and 1 had progressive
      disease, and the response rate was 68% (15/22). The median survival time was 17
      months, and 1-, 2-, and 3-year survival rates were 59%, 26%, and 13%,
      respectively. Progressive disease was the reason for treatment discontinuation in
      10 (45%) of the 22 patients, and 9 (41%) patients had to stop the treatment
      because of complications. Systemic toxicity was minimal. The pharmacokinetic
      study showed a high degree of hepatic extraction for both cisplatin and 5
      fluorouracil during the treatment. CONCLUSIONS: The treatment regimen described
      herein thus appears to be efficacious regarding the tumor response and survival
      for patients with unresectable liver metastases from colorectal cancer.

PMID- 11821800
TI  - The mechanisms of angiogenesis in hepatocellular carcinoma: angiogenic switch
      during tumor progression.
AB  - Solid tumors constantly require a vascular supply for their progression and
      metastasis. Hepatocellular carcinoma (HCC) is known to gain its hypervascularity
      during the process of dedifferentiation and progression. Various angiogenic
      growth factors and inhibitors regulate this angiogenic switch of HCC. The known
      endothelial cell-specific growth factors and their receptors can be classified
      into the vascular endothelial growth factor and angiopoietin families. Both
      vascular endothelial growth factors and angiopoietins have been found to work
      cooperatively, and both are essential for HCC angiogenesis. Because small and ill
      vascularized HCCs slowly progress and only rarely metastasize, antiangiogenic
      therapy could therefore be a promising anticancer strategy for HCC.

PMID- 11821801
TI  - Oncogenic signal transduction and therapeutic strategy for hepatocellular
      carcinoma.
AB  - Discoveries of oncogenic signaling molecules lead to the comprehension of
      molecular mechanisms of tumor progression, as well as to the development of novel
      therapeutic tools for hepatocellular carcinoma. We have identified critical
      functions of intracellular signals transmitted from insulin-like growth factor
      and Wnt oncoprotein in carcinogenesis. The insulin-like growth factor system
      activates a number of signaling cascades resulting not only in hepatic
      mitogenesis, but also in cell survival. The secreted oncoprotein Wnt transforms
      beta-catenin potentials as a component of cell adhesion complexes with cadherins,
      into a transcription factor in the nucleus. Here, the important role of such
      signal transduction is reviewed, and we emphasize its control as a promising
      approach for the treatment of hepatocellular carcinoma.

PMID- 11821802
TI  - Clinicopathologic risk factors for recurrence after a curative hepatic resection
      for hepatocellular carcinoma.
AB  - BACKGROUND: The long-term prognosis after resection for patients with
      hepatocellular carcinoma is still unsatisfactory because of the high recurrence
      rate. The survival of patients with multiple intrahepatic or extrahepatic
      recurrence is especially poor. METHODS: Among the patients who underwent hepatic
      resection for hepatocellular carcinoma between 1981 and 2000, 216 patients with 3
      or less than 3 intrahepatic recurrences (group B); 156 patients with more than 3
      intrahepatic recurrences, extrahepatic recurrences, or both (group C); and 51
      patients who survived more than 5 years without recurrence (group A) were
      clinicopathologically studied. RESULTS: The period to recurrence of group C was
      significantly earlier than that of group B and also showed a significantly poor
      prognosis after recurrence. Tumor factors, including size, portal venous
      invasion, intrahepatic metastasis, histologic grade, or the number of tumors at
      resection in group C was significantly worse than in groups A and B. Although no
      differences are recognized in the tumor factors between groups A and B, except
      for the alpha-fetoprotein level, liver function in group B was significantly
      worse than that in group A. In addition, the frequency of hepatitis B surface
      antigen in group B and that of hepatitis C virus in group B was significantly
      less and higher than that in group A, respectively. CONCLUSION: Similar to
      extrahepatic metastasis, multinodular recurrences are also mainly caused by
      metastatic recurrence from the main tumor by means of the portal system, and
      recurrences with up to 3 intrahepatic nodules are mainly caused by metachronous
      multicentric hepatocarcinogenesis. Because the mechanisms of recurrence differed,
      determining the patterns of recurrence on the basis of the clinicopathologic
      findings is important for selecting the optimal postoperative therapy for each
      individual patient.

PMID- 11821803
TI  - A 16-year experience in performing hepatic resection in 303 patients with
      hepatocellular carcinoma: 1985-2000.
AB  - BACKGROUND: Hepatic resection is an accepted therapeutic modality for
      hepatocellular carcinoma (HCC). Over the past 2 decades, liver surgery has
      evolved to a refined and deliberate operation. In the present study surgical
      results are analyzed with an aim toward further improving the treatment of HCC.
      METHODS: We studied 303 patients with HCC who underwent a hepatic resection at 2
      university hospitals from 1985 through 2000. Living-related liver transplantation
      was a procedure of choice in 1 patient with early staged HCC. Fifty-five percent
      of the patients had associated cirrhosis. Before the operation, the liver
      function was mainly evaluated with the indocyanine green retention test. RESULTS:
      The mortality rate within 30 days after the operation was 1.6%. One-, 3-, 5-, 10
      , and 15-year cumulative survival rates were 84%, 67%, 51%, 20%, and 11%,
      respectively. The tumor stage I and II groups showed superior survival rates to
      those of the tumor stage III and IV groups, respectively, and the difference was
      statistically significant. The disease-free survival curves, however, showed the
      rate to be 27% at 5 years and 11% at 10 years. CONCLUSIONS: Although the surgical
      results have greatly improved in the treatment of HCC, the recurrence rate is
      still high. In carefully screened patients with poor liver function and small
      HCC, liver transplantation enhances the possibility of cure.

PMID- 11821804
TI  - Intrahepatic cholangiocarcinoma: its mode of spreading and therapeutic
      modalities.
AB  - Intrahepatic cholangiocarcinoma (IHCC) is a primary adenocarcinoma of the liver,
      arising from the intrahepatic bile ducts. The prognosis is generally poor because
      locoregional extension is usually advanced at the time of diagnosis. Even after a
      resection, the outcome for patients with advanced IHCC is extremely poor, and the
      presence of lymph node metastasis has been reported in most previous studies to
      be the worst prognostic factor after a resection. There are no clear guidelines
      on lymph node dissection with IHCC. In this article, we review the mode of
      invasion and the therapeutic modalities: hepatic resection, lymph node
      dissection, liver transplantation, radiation, and chemotherapy for IHCC.

PMID- 11821805
TI  - Pathogenesis of portal hypertensive gastropathy: a clinical and experimental
      review.
AB  - Portal hypertensive gastropathy (PHG) is recognized as a clinical entity in
      portal hypertension, but the pathogenesis of PHG is still unclear. Therefore, we
      reviewed the current state of knowledge concerning the portal hypertensive
      gastric mucosa and hypothesized the pathogenesis of PHG. Elevated portal pressure
      can induce changes of local hemodynamics, thus causing congestion in the upper
      stomach and gastric tissue damage. These changes may then activate cytokines and
      growth factors, such as tumor necrosis factor alpha, which are substances that
      activate endothelial constitutive nitric oxide synthase and endothelin 1 in the
      portal hypertensive gastric mucosa. Overexpressed nitric oxide synthase produces
      an excess of nitric oxide, which induces hyperdynamic circulation and
      peroxynitrite overproduction. The overproduction of peroxynitrite, together with
      endothelin overproduction may cause an increased susceptibility of gastric mucosa
      to damage. When combined with the characteristics of impaired mucosal defense and
      healing, these factors may together produce PHG in patients with portal
      hypertension.

PMID- 11821806
TI  - Endoscopic injection sclerotherapy in the management of 2105 patients with
      esophageal varices.
AB  - BACKGROUND: The objective of this study is to examine the overall clinical
      results of endoscopic injection sclerotherapy (EIS) for patients with esophageal
      varices in our institution. METHODS: From January 1982 to May 2001, 2105 patients
      with esophageal varices were treated with EIS, which included prophylactic
      injections for patients with risky varices according to our criteria. Follow-up
      endoscopy was performed every 3 months, and recurrent varices were treated with
      additional EIS. RESULTS: Acute variceal bleeding was controlled in 468 of 473
      patients (98.9%). Esophageal varices were completely eradicated in 1757 of 2105
      patients (83.5%) with 3.8 +/- 1.6 sessions of EIS. The cumulative recurrence
      rates were 32.2% at 5 years, 36.5% at 10 years, and 37.8% at 15 years. The
      cumulative nonbleeding rates were 92.3% at 5 years, 90.1% at 10 years, and 89.5%
      at 15 years. The survival rate of acute bleeders was significantly lower than for
      both elective and prophylactic cases (P <.05). The overall cumulative survival
      rate was 28.2% at 10 years. CONCLUSIONS: EIS is the first choice of treatment for
      esophageal variceal bleeding, and rebleeding was shown to be well controlled in a
      long-term follow-up with endoscopy and additional EIS. The lower survival rate
      observed in acute bleeders may therefore justify the use of prophylactic EIS.

PMID- 11821807
TI  - Long-term results of endoscopic Histoacryl injection sclerotherapy for gastric
      variceal bleeding: a 10-year experience.
AB  - BACKGROUND: The long-term efficacy and safety of endoscopic injection of N-butyl
      2-cyanoacrylate (Histoacryl) were evaluated as the initial treatment for bleeding
      gastric varices. PATIENTS AND METHODS: Fifty-two patients with bleeding gastric
      varices underwent endoscopic injections of Histoacryl for hemostasis over a 10
      year period. Histoacryl was injected intravariceally. Among these 52 patients, 32
      had active bleeding and 20 had recent bleeding. Most of the varices were large
      (F2 or F3, 48 cases). After Histoacryl injection, the patients were followed
      endoscopically with retreatment administered as necessary. The patients were
      followed for a mean 28.1 months. RESULTS: The rate of initial hemostasis (no
      bleeding occurred for 48 hours after sclerotherapy) was 96.2%. Cumulative
      nonbleeding rates were 64.7%, 52.7%, and 48.2% at 1, 5, and 10 years,
      respectively. When rebleeding occurred, 80.0% was within 1 year after initial
      injection. Recurrent bleeding was easily stopped with the reinjection of
      Histoacryl in most patients. The treatment failure-related mortality rate was
      4.0% (2 of 52). The cumulative survival rates were 66.9%, 60.4%, and 55.5% at 1,
      5, and 10 years, respectively. The mortality depended on either malignancy or
      liver function (Child-Pugh classification). CONCLUSIONS: These results suggest
      that Histoacryl injection sclerotherapy is highly effective for the treatment of
      bleeding gastric varices, with rare complications occurring both acutely and long
      term. Therefore, Histoacryl injection sclerotherapy is considered to be the first
      choice of treatment for bleeding gastric varices, but the rate of recurrent
      bleeding is so high that further methods or devices still need to be developed in
      order to prevent gastric variceal rebleeding.

PMID- 11821808
TI  - Living-donor liver transplantation for fulminant hepatic failure in adult
      patients with a left-lobe graft.
AB  - BACKGROUND: Living donors are practically the only source of organs in countries
      where the availability of cadaveric donors is severely restricted, such as Japan.
      A left-lobe graft, in which one third of the liver is donated, is therefore used
      for adult-to-adult living-donor liver transplantation (LDLT) in patients with
      fulminant hepatic failure (FHF). METHODS: Fifteen adult patients with FHF,
      ranging from 22 to 59 years of age, were treated with LDLT with a left-lobe
      graft. Preoperative encephalopathy was grade II in 2 patients, grade III in 4
      patients, and grade IV in 9 patients. The graft volume (GV) ranged from 260 to
      570 mL, thus corresponding to 23% to 54% of the recipients' standard liver volume
      (SLV). The patients were divided into 2 groups according to their GV/SLV: a
      medium-size graft group (GV/SLV > or =30%; group M, n = 11) and a small-size
      graft group (GV/SLV <30%; group S, n = 4). The effects of GV/SLV on graft
      function and survival were compared. Postoperative neurologic complications were
      also evaluated. RESULTS: The donors are all doing well. Twelve (80%) of the 15
      recipients are still alive, with a follow-up period of from 3 to 43 months. No
      statistically significant differences were observed in the postoperative serum
      levels of bilirubin and alanine aminotransferase, prothrombin time, or frequency
      of postoperative complications between the 2 groups. The graft and patient
      survival rates were 75% (3/4) and 75% (3/4) in group S and 73% (8/11) and 82%
      (9/11) in group M, respectively. All patients who survived the perioperative
      period recovered without any neurologic sequelae. CONCLUSIONS: The high success
      rate and low donor risk of LDLT may therefore justify its use for adult patients
      with FHF using a left-lobe graft.

PMID- 11821809
TI  - Liver transplantation for hepatocellular carcinoma.
AB  - The surgical management for hepatocellular carcinoma (HCC) is multiplicity. In
      Japan, liver resection has generally been considered to be the only curative
      treatment for HCC. The resectability of a tumor in cirrhotic patients, however,
      is limited by the diminished functional reserve of the cirrhotic liver and the
      attendant risk for intraoperative bleeding and postoperative liver failure. In
      cirrhotic patients, liver transplantation has been considered as the indication
      for HCC in many countries except Japan. Although the survival rate of patients
      with HCC who received liver transplants was poor in the early period, it later
      moved to the same level as for patients with other liver diseases. In 1993,
      living donor adult liver transplantation was started in Japan and it became an
      additional option for the treatment of HCC. A shortage of liver donors means that
      new methods of liver procurement must be explored. Domino liver transplantation
      using the livers of patients with familial amyloid polyneuropathy was also
      another option for advanced HCC. For the prevention of a recurrence of HCC, pre-,
      intra-, and postoperative chemotherapy have been performed after both liver
      resection and liver transplantation. We should also try to minimize
      intraoperative dissemination by surgical manipulation. Recently, potential gene
      therapies for HCC have been studied. Electroporation-mediated IL-12 gene therapy
      for HCC was found to be effective for both mIL-12-transferred HCC and for distant
      HCC. For patients with HCC accompanied by liver cirrhosis, liver transplantation
      remains the ultimate curative therapy. Immunologic and oncologic approaches to
      HCC can help prevent tumor recurrence and also help us to obtain better results
      after liver transplantation.

PMID- 11821811
TI  - Hepatic artery reconstruction in living-donor liver transplantation: a review of
      its techniques and complications.
AB  - BACKGROUND: Hepatic arterial reconstruction is one of the most difficult
      procedures in living-donor liver transplantation (LDLT) because the artery used
      is generally small in diameter and has a short stalk. If hepatic artery
      thrombosis (HAT) occurs, the recipient clinical course will be unstable. The
      introduction of microvascular hepatic arterial reconstruction has significantly
      decreased the incidence of HAT. METHODS: Fifty-two cases of LDLT were performed
      from October 1995 to May 2001 in our institution. Hepatic arterial reconstruction
      was performed under microscopic guidance. RESULTS: HATs were recognized in 2
      cases (3.8%), both of which needed reoperation. CONCLUSIONS: Surgeons who perform
      hepatic arterial reconstruction in LDLT should be highly trained in microvascular
      techniques to decrease the incidence of HAT. This commentary reviews the surgical
      techniques of hepatic arterial reconstruction and possible complications that may
      arise in a reconstructed hepatic artery.

PMID- 11821810
TI  - Perioperative management and complications in donors related to living-donor
      liver transplantation.
AB  - BACKGROUND: Living-donor liver transplantation has become a legitimate
      alternative to cadaveric liver transplantation. However, information on the
      perioperative management of donors is still scarce. METHODS: Between October 1996
      and May 2001, 52 consecutive living-donor liver transplantations have been
      performed at the authors' institution. The preoperative and postoperative
      management of donors, operative technique, and complications are herein
      described. RESULTS: All donors were discharged from the hospital alive and well,
      and all returned to their normal lifestyle without any significant adverse
      sequelae after a mean hospital stay of 13 days after the operation. Overall, 24
      complications occurred, all of which could be managed conservatively, except for
      one case of hepatic duct stricture that required a relaparotomy. A learning curve
      has been observed in terms of blood loss during donor hepatectomy. CONCLUSIONS:
      These results indicate that our approach toward the selection and management of
      donors was appropriate. Because of the use of meticulous operative techniques,
      blood loss could also be minimized.

PMID- 11821812
TI  - Auxiliary partial orthotopic liver transplantation from living donors.
AB  - Auxiliary liver transplantation was originally started in Western countries in
      the form of heterotopic auxiliary liver transplantation for end-stage liver
      disease. It thereafter developed into the form of auxiliary partial orthotopic
      liver transplantation for acute liver failure. In Japan, where living-donor liver
      transplantation is the main mode of liver transplantation, auxiliary partial
      orthotopic liver transplantation was initially used for patients with metabolic
      liver diseases and has since developed into an effective solution for small-for
      size living donor grafts. Although there has been a reported case of successful
      auxiliary partial orthotopic liver transplantation from a living donor for the
      treatment of acute liver failure, wide application of this technique is made
      difficult at present by such unsolved problems as functional competition, small
      graft size, severe clinical status, and toxic liver syndrome. Auxiliary partial
      orthotopic liver transplantation from a living donor is an established procedure
      for small-for-size living-donor grafts and metabolic liver diseases, and the
      future establishment of its successful application to cases of acute liver
      failure is anticipated.

PMID- 11821813
TI  - Detection of micrometastasis in the sentinel lymph nodes in breast cancer.
AB  - BACKGROUND: The axillary lymph node (ALN) status is still the most important
      prognostic factor in the staging and treatment of breast cancer. Intraoperative
      lymphatic mapping and sentinel lymphadenectomy techniques were investigated in
      patients with early-stage breast cancer who did not have clinically palpable
      ALNs. METHODS: Forty-four patients with breast cancer underwent a sentinel lymph
      node biopsy (SLNB), followed by a complete axillary lymphadenectomy. Sentinel
      lymph nodes (SLNs) were detected by means of so-called 2-way mapping with
      coloring matter and an isotope. Our standard protocol for evaluating metastasis
      in SLNs included a frozen section at 1 level for reverse transcription polymerase
      chain reaction (RT-PCR), plus a paraffin section at 1 level for
      immunohistochemistry (IHC) of cytokeratin 19, while the rest were evaluated by
      hematoxylin-eosin (H&E) staining. RESULTS: SLNs were identified in 42 (95%) of 44
      patients. Twenty-one patients had no metastasis in SLNs; however, ALN metastasis
      was found in 3 patients. Of these 3 patients, 2 had micrometastasis detected by
      means of either IHC or RT-PCR. Therefore the false-negative rate was decreased
      from 7% (3/44) to 2% (1/44). Furthermore, of the remaining 18 ALN-negative
      patients, micrometastasis was detected by means of either IHC or RT-PCR in 7
      (39%) patients. CONCLUSION: We suggest that SLNB is recommended to detect
      micrometastasis by means of H&E staining, IHC, and RT-PCR. Omitting ALN
      dissection referred by SLNB should be avoided if SLNs were evaluated only by H&E
      staining, and/or IHC without RT-PCR.

PMID- 11821814
TI  - Metastatic breast cancer with HER2/neu-positive cells tends to have a morbid
      prognosis.
AB  - BACKGROUND: Clinically, human epidermal growth factor receptor 2 (HER2)
      overexpression is associated with a faster rate of tumor growth and an increased
      rate of metastasis, and a patient who is HER2 strongly positive tends to have a
      poor prognosis and a decreased disease-free survival and overall survival (OS)
      time. METHODS: We analyzed data on 526 Japanese adult women with breast cancer
      with respect to the relationship between the status of HER2/neu receptor
      expression and the recurrent state and survival from detection of the first
      recurrence. All these women were treated from 1982 to 2000 in the Department of
      Surgery, National Beppu Hospital, Kyushu, Japan. In 95 patients with metastatic
      breast cancer after curative resection, the expression of HER2/neu status was
      examined by using immunohistochemical staining methods (HercepTest). Scores of 0,
      1+, 2+, and 3+ were given according to the HercepTest data. Only scores of 2+ and
      3+ were assessed as an overexpression of HER2/neu protein and HER2-positive
      patients. Between the HER2-positive and HER2-negative patients, the survival
      after surgical intervention, the disease-free survival time, and the survival
      time after the initial recurrence were compared. RESULTS: An overexpression of
      HER2/neu receptor protein occurred at a rate of 23.7% (23/97) in the 97 women
      with metastatic breast cancer. There was no difference in age, tumor size, TN
      staging system, and the number of lymph node metastases between HER2-positive and
      HER2-negative patients. Almost all HER2-positive patients had a negative estrogen
      receptor status (14/15 [93.3%]). The initial sites of recurrence were classified
      as (1) soft tissue, bone, and viscera or (2) soft tissue, bone, lung-pleura,
      liver, and brain. For the HER2-positive patient, viscera, especially the liver
      and lung, were predominant initial sites of recurrence. Survival rates, OS,
      disease-free survival time, and time after first recurrence were all analyzed.
      Although there was no difference in disease-free survival time, there were
      significant differences between the HER2-positive and HER2-negative groups in OS
      and the time after initial recurrence. CONCLUSIONS: Metastatic breast cancer with
      overexpression of HER2/neu tends toward a poor prognosis, especially after the
      first recurrence. For such patients with metastatic breast cancer, a high-dose
      anthracycline-containing regimen might be needed.

PMID- 11821815
TI  - Clinical significance of PEA3 in human breast cancer.
AB  - BACKGROUND: Recently, PEA3 has been reported to suppress HER-2/neu overexpression
      by promoter activity and thereby inhibit tumorigenesis of breast cancer both in
      vitro and in vivo. METHODS: The expression of PEA3 and the clinicopathologic
      features of 89 patients with breast cancer were investigated. The expression of
      PEA3 was immunohistochemically detected in 42 (47.2%) of 89 patients. RESULTS:
      The correlation between the expression of PEA3 and the clinicopathologic features
      were nil with regard to lymph node metastasis, hormone receptor, blood vessel
      invasion, and lymphatic vessel invasion. The disease-free survival rate was
      shorter for the PEA3-negative groups than for the PEA3-positive ones, but with no
      statistically significant difference. The overall survival rate after surgical
      resection in patients who were PEA3-positive vs PEA3-negative was 100% vs 87.2%,
      respectively, at 3 years and 89.8% vs 72.7%, respectively, at 6 years (P =.0472).
      CONCLUSIONS: The expression of PEA3 in breast cancer might therefore be a novel
      prognostic factor.

PMID- 11821816
TI  - Micrometastasis in the bone marrow of patients with lung cancer associated with a
      reduced expression of E-cadherin and beta-catenin: risk assessment by
      immunohistochemistry.
AB  - BACKGROUND: The presence of disseminated tumor cells in bone marrow is considered
      to be a premetastatic state, which is called micrometastasis. To evaluate the
      relationship between micrometastasis and cellular adhesion molecules in the
      primary lesion, E-cadherin and beta-catenin were immunohistochemically
      investigated. Methods. Fifty-eight patients with non-small cell lung cancer who
      underwent a complete resection were entered into this study. Tumor cells in bone
      marrow aspirates were detected by immunohistochemistry using cytokeratin (CK) 18.
      Immunohistochemical studies of E-cadherin and beta-catenin were performed in the
      corresponding primary tumor. RESULTS: CK-positive cells were detected in the bone
      marrow aspirates from 27 of 58 patients. A reduced expression of the E-cadherin
      and beta-catenin was found in 16 (27.6%) and in 22 (37.9%) of 58 patients,
      respectively. In 26 cases with a reduced expression of E-cadherin and/or beta
      catenin, 16 cases had CK-positive cells, whereas 11 of 32 cases with normal
      expression of both factors had CK-positive cells (P=.0392). The patients with
      micrometastasis demonstrated an earlier recurrence (P =.0642) and a significantly
      poorer survival (P =.0437) than those without such cells. CONCLUSIONS:
      Micrometastasis in the bone marrow might be a significant predictor of poor
      prognosis, and a reduced expression of E-cadherin and beta-catenin are important
      determinants for the metastatic capability of individual cancer cells.

PMID- 11821817
TI  - Immunologic strategies for the treatment of non-small cell lung cancer.

PMID- 11821818
TI  - Clinical significance of serum TH1/TH2 cytokines in patients with pulmonary
      adenocarcinoma.
AB  - BACKGROUND: The acquisition of immune reaction in the peripheral blood is
      expected to play a critical role in the prevention of tumor progression. However,
      the clinical role of the circulating immune response against human cancer remains
      unclear. METHODS: Serum samples from 68 consecutive patients who underwent
      resection for pulmonary adenocarcinoma were obtained before the operation. The
      serum levels of interferon gamma and interleukin 4 were measured and the impact
      on the clinical features was assessed. According to the predominance of the
      cytokine levels, the patients were classified into 4 groups: interferon gamma
      only (T(H)1), interleukin 4 only (T(H)2), both (T(H)0), and neither (T(H)X).
      RESULTS: In the T(H)1 group, 18 of 22 patients (81.8%) were free from lymph node
      metastasis, whereas 5 of 7 patients (71.4%) in the T(H)2 group had lymph node
      involvements. As a result, 62 patients underwent complete resection, with 9 of 19
      patients (47.3%) in the T(H)1 group having recurrence, but no relapse of the
      disease appearing in the T(H)2 group during the observation period. The disease
      free interval for the T(H)2 group was significantly longer than that for the
      T(H)1 group (44.2 mo vs 26.1 mo, P =.03). CONCLUSIONS: Assessing the serum T(H)
      profile on the basis of the predominance of the serum interferon gamma or
      interleukin 4 is important to presume the ongoing responses of T cells against
      the tumor burden.

PMID- 11821819
TI  - A time trend of profile and surgical results in 1123 patients with non-small cell
      lung cancer.
AB  - BACKGROUND: A time trend for characteristics and prognoses of patients with non
      small cell lung cancer (NSCLC) who underwent surgical resection was investigated.
      METHODS: A series of 1123 consecutive patients with NSCLC who underwent surgical
      resection from 1975 to 1998 was reviewed with respect to changes in patient
      profile and surgical outcome among subgroups classified by clinicopathologic
      factors. RESULTS: With time, the proportion of female, elderly (> or =70 years),
      pathologic stage IA, nonsmoking, and adenocarcinoma patients increased
      significantly whereas pneumonectomy, incomplete resection, and pathologic stage
      IIIA patients decreased significantly. Overall survival showed an upward trend
      with 5-year survival rates of 30.0% in the 1970s, 41.6% in the 1980s, and 50.1%
      in the 1990s (P <.0001). This tendency was similar in every pathologic stage that
      was observed. The proportion of female patients with adenocarcinoma that
      exhibited the most favorable prognosis among subpopulations classified by gender
      and cell types was significantly higher in the 1990s (28.0%) than in the 1970s
      (14.0%). Multivariate analysis revealed that female gender, adenocarcinoma,
      complete resection, and early pathologic stage were independently favorable
      factors whereas advanced age was an unfavorable factor. CONCLUSIONS: The improved
      survival following surgical resection for NSCLC during the study period was
      associated with an increasing population of female patients with adenocarcinoma,
      more detection of early disease, and effective elimination of unresectable cases.

PMID- 11821820
TI  - Differences in endothelial function and morphologic modulation between canine
      autogenous venous and arterial grafts: endothelium and intimal thickening.
AB  - BACKGROUND: Late graft failure is still a problem for vascular surgeons. A
      previous study showed superior patency of arterial grafts compared with venous
      grafts. In this review we discuss the differences in functional and morphologic
      modulation of experimental autogenous venous and arterial grafts. RESULTS: In
      canine venous grafts, the endothelium of the graft was denuded and recovered
      within 3 or 4 weeks. In contrast, in arterial grafts, denudation of the
      endothelium was minimal, and no platelet adherence was observed. Instead, nearly
      normal intact endothelial cell surface had covered the intima within 3 days after
      grafting. The histologic findings for arterial grafts thus were quite different
      from those for venous grafts. Different responses to flow changes between venous
      and arterial grafts were observed. In the venous grafts, pronounced intimal
      thickening was associated with impairment of endothelial responses, whereas in
      the arterial grafts, intact endothelial function and no intimal thickening were
      observed. CONCLUSIONS: The intact endothelial function and absence of intimal
      thickening under the arterial grafts may explain the superior patency of
      autogenous arterial grafts in comparison with venous grafts.

PMID- 11821821
TI  - Local blood serotonin and soluble P-selectin levels during percutaneous
      transluminal balloon angioplasty and primary stenting of the iliac artery.
AB  - BACKGROUND: The activation of platelets or leukocytes plays an important role in
      development of intimal hyperplasia. We investigated whether the local blood
      serotonin and soluble P-selectin levels changed during endovascular therapy of
      the iliac artery. METHODS: Blood samples were obtained from the iliac artery of
      18 lower limbs undergoing percutaneous balloon angioplasty alone (8 limbs, group
      I) or percutaneous balloon angioplasty and primary stenting (10 limbs, group II).
      The serotonin levels in platelet-poor plasma were measured in all limbs. In group
      I the urinary level of the serotonin metabolite 5-hydroxyindoleacetic acid was
      also measured 24 hours before and 24 hours after the procedures. The soluble P
      selectin levels were measured in the 6 patients in group II. RESULTS: Before
      angioplasty the mean (+/- SEM) serotonin concentrations were 1.2 +/- 0.2, 1.2 +/-
      0.4, and 1.2 +/- 0.3 ng/mL in all cases, group I, and group II, respectively.
      After angioplasty these values changed to 1.7 +/- 0.4 (P =.0750), 1.2 +/- 0.4 (P
      =.8001), and 2.1 +/- 0.6 ng/mL (P =.0529), respectively. In group I urinary 5
      hydroxyindoleacetic acid concentrations 24 hours before and 24 hours after the
      procedures were 0.0026 +/- 0.0004 and 0.0031 +/- 0.0006 mg/mg creatinine,
      respectively (P =.2566). In group II the soluble P-selectin levels significantly
      increased after intervention, from 26.0 +/- 5.7 to 33.9 +/- 5.3 ng/mL (P =.0296).
      CONCLUSIONS: Although the serotonin levels did not change significantly, the
      soluble P-selectin levels increased significantly after intervention. Leukocyte
      activation may therefore contribute to the progression of restenosis after
      peripheral endovascular therapy.

PMID- 11821822
TI  - Gene therapy in vascular surgery comes of age.
AB  - In the last decade, gene therapy for cardiovascular diseases has been becoming a
      reality. However, although numerous successful experimental studies have
      suggested possible strategies of gene therapy for cardiovascular disorders, the
      clinical outcome remains limited. Because cardiovascular diseases are the result
      of complex causes, there is no exact answer to the following question: Which is
      the best gene to treat vascular diseases? In addition, current limitations
      include less clinically relevant vectors regarding both gene-transfer efficiency
      and safety, and at present, most efforts are focused on identifying more
      effective therapeutic genes, as well as developing more effective vectors.
      Furthermore, greater pathophysiologic understanding of these diseases, including
      vein-graft remodeling and ischemic limbs, is required. Regarding the relevant
      vector, we recently developed a novel mononegavirus-based gene-transfer vector,
      namely recombinant Sendai virus, which has shown dramatically superior gene
      transfer efficiency to other vectors, including adenovirus, in several organs
      (eg, the vessel wall and skeletal muscles). These efforts now offer new
      possibilities to get more fruits in the field of gene therapy for vascular
      surgery.

PMID- 11821823
TI  - Comparison of the long-term results between surgical and conservative treatment
      in patients with intermittent claudication.
AB  - BACKGROUND: The optional therapeutic strategy for patients with intermittent
      claudication remains controversial. In this study, we investigated the influence
      of surgical and conservative therapies on improving the quality of life in
      patients with intermittent claudication. METHODS: We analyzed 427 patients who
      were admitted to our hospital with intermittent claudication in their legs during
      a 15-year period from January 1984 to December 1999. We separated them into 2
      groups; 259 patients (362 legs) were treated surgically and 168 patients were
      treated conservatively. RESULTS: At the suprainguinal and infrainguinal (above
      knee) region, the surgery group showed significantly better rate of improvement
      than did the conservative group, but in the infrainguinal (below knee) region,
      there was no significant difference between the 2 groups. The 3-year and 5-year
      patency rates for the arterial reconstruction of the suprainguinal and
      infrainguinal region was satisfactory, but that of the infrainguinal region was
      not very good even if an auto vein graft was used. CONCLUSIONS: Aggressive
      surgical treatment is therefore recommended in patients whose distal anastomotic
      region is above the knee, because there are great benefits from surgical
      reconstruction. However, in patients whose distal anastomotic region is below the
      knee, conservative treatment might be just as effective as surgery.

PMID- 11821824
TI  - Changing profile of parenteral nutrition in pediatric surgery: a 30-year
      experience at one institute.
AB  - BACKGROUND: Due to technical refinements and steady advances in the development
      of highly sophisticated nutrient solutions consisting of optimal combinations of
      macronutrients and micronutrients, parenteral nutrition (PN) is now playing an
      important role in patient management. However, some PN-associated complications,
      such as catheter-related sepsis (CRS) and cholestasis, continue at high
      incidence, particularly in neonates. The objective of this study was to
      investigate the changing profiles of PN over the past 30 years in our department.
      METHODS: The medical records of 893 children (225 neonates, 245 infants, 261
      preschool-age children, and 162 school-age children) who were placed on PN for >7
      days in our department were reviewed, and the following data were extracted:
      birth weight, underlying disease, indications for PN, PN delivery route, type of
      catheter used, duration of PN, substrate and energy intake, type of amino acid
      solution used, and incidence of complications including CRS and liver
      dysfunction. The results were analyzed by dividing the patients into 3 groups
      according to their basic stages in management of PN and consisted of group 1
      (1970 to 1979), group 2 (1980 to 1989), and group 3 (1990 to 1999). The
      parameters were compared in each group. RESULTS: The total number of patients in
      each group showed no significant difference; however, the percentage of low birth
      weight neonates increased in group 3. In group 1, 85% of PN was administered
      through the peripheral vein; in group 2, 51.2%; and in group 3, 9.7%. The total
      calorie and nutrient intake decreased in groups 2 and 3 compared with group 1,
      particularly regarding fat intake. In groups 1 and 2, commercially available
      amino acid solution based on the Food and Agriculture Organization/World Health
      Organization formula was usually used as the nitrogen source, but in group 3, it
      was changed to an amino acid solution for children. CRS decreased significantly,
      particularly in neonates, and occurred at a rate of 45.4% in group 1, 10.7% in
      group 2, and 1.5% in group 3. The incidence of liver dysfunction also showed a
      decrease: 35.7% in group 1, 22.3% in group 2, and 18.0% in group 3. A
      multivariate analysis showed a strong relationship between PN-related liver
      dysfunction and the duration of PN, the presence of infection, and the type of
      amino acid solution used. CONCLUSIONS: PN via central venous catheters has been
      regarded as safe and effective treatment in pediatric surgical patients. Over the
      past 30 years, the incidence of CRS has decreased. However, PN-related liver
      dysfunction remains a problem, particularly in patients receiving long-term PN.

PMID- 11821825
TI  - Evaluation of genetic heterogeneity in neuroblastoma.
AB  - BACKGROUND AND METHODS: The prognosis in neuroblastoma, which is the most common
      solid tumor in children, tends to vary greatly, and many studies have
      demonstrated both clinical and biological factors to be closely correlated with
      the outcome. In order to select the optimal treatment according to the degree of
      malignancy of neuroblastoma, it is essential to accurately and rapidly identify
      any genetic heterogeneity associated with the prognosis. We assessed the status
      of some genetic abnormalities (MYCN amplification, deletion of the short arm of
      chromosome 1, DNA ploidy, and a gain of the chromosome 17q region) associated
      with the prognosis using several molecular biological methods. RESULTS AND
      CONCLUSIONS: The combination of several molecular biological techniques is thus
      considered to be useful for elucidating the degree of malignancy of
      neuroblastoma. In particular, diagnostic analyses based on a combination of the
      fluorescence in situ hybridization (FISH) method and the quantitative polymerase
      chain reaction (PCR) method may be considered to be the most effective methods
      for quickly and accurately evaluating any aberrations in the gene dosages
      associated with the patients' outcomes.

PMID- 11821826
TI  - Electrophysiological properties of the aganglionic segment in Hirschsprung's
      disease.
AB  - BACKGROUND: In Hirschsprung's disease, the severity of bowel obstruction varies
      among those patients who have the affected colon of a similar length, suggesting
      that there is more than a simple aperistaltic obstruction in the pathophysiology
      of Hirschsprung's disease. METHODS: A series of our electrophysiological studies
      of the aganglionic segments from human specimens and rat models were reviewed to
      obtain an overview of Hirschsprung's disease. RESULTS: In human studies, a
      generation of regular spontaneous activity was recorded in both the dilated
      ganglionic segment and transitional aganglionic region, while the smooth muscle
      cells of the narrow aganglionic segment were electrically quiescent. According to
      a pattern of innervation, in the dilated ganglionic segment inhibitory junction
      potentials associated with or without excitatory junction potentials were
      observed in all of the examined cells, and these intrinsic nervous inputs were
      gradually decreased in the transitional region. In the narrow aganglionic
      segment, only excitatory junction potentials of the extrinsic nervous origin were
      found in about 20% of the examined cells In rat models, distally increasing
      tendency of the excitatory nervous inputs was observed in the narrow aganglionic
      segment. CONCLUSION: A bowel obstruction in Hirschsprung's disease might be
      generated due to complex mechanisms involving myogenic and neurogenic
      abnormalities.

PMID- 11821827
TI  - Segmental small-intestinal transplantation: a comparison of jejunal and ileal
      grafts.
AB  - Strong immune responses, such as rejection and graft-versus-host disease, have
      been major obstacles to achieving a successful intestinal transplantation.
      Segmental small-intestinal transplantation is considered to result in a weaker
      response than total length grafting. Problems relating to organ harvesting from a
      living donor and spacial constraints of the recipient's abdominal cavity are the
      other reasons why a segmental small intestinal transplantation is required. It is
      also important to select the most suitable part of the intestine to be used in
      transplantation; therefore, the jejunal and ileal grafts were comparatively
      reviewed from the aspects of native bowel characteristics, function,
      preservation, and immunological response. Immunologically, the jejunum is
      considered to have a slight advantage over the ileum. However, the control of
      rejection does not become inordinately more difficult for ileal grafts.
      Functionally, the ileum is considered to be better with regard to several
      parameters, such as greater absorptive capacities of fat, bile acids, and
      vitamins, and adaptation potential. Anatomically, an ileal graft is feasible for
      living-related transplantation. However, there is no conclusive factor for
      choosing the ileum as a suitable segmental graft. Further extensive studies are
      still needed to clarify various experimental as well as clinical aspects
      regarding intestinal transplantation.

PMID- 11821828
TI  - Effects of the prenatal administration of cimetidine on testicular descent and
      genital differentiation in rats.
AB  - BACKGROUND: Cimetidine has been shown to induce gonadal and sexual dysfunction in
      men. This study aimed to clarify the effect of cimetidine on testicular descent
      and genital development in utero. METHODS: Pregnant rats (280 to 330 g) were
      separated into 4 groups. In group 1, the rats were injected subcutaneously with a
      dose of 600 mg/kg of cimetidine twice on days 15, 16, 17, and 18 of gestation. In
      group 2, the rats were injected with a dose of 300 mg/kg of cimetidine twice in
      the same way as in group 1. In group 3, the rats were injected with a dose of 150
      mg/kg of ranitidine twice in the same manner as in the above groups. In group 4,
      the rats were injected with the same volume of saline. At birth the anogenital
      distance was measured, and the incidence of testicular descent was examined in
      male offspring at 90 days of age. Next, the testes were weighed and
      histologically examined. The chi-square test and Student t test were used to
      perform statistical analyses of the results. RESULTS: At birth, the anogenital
      distance (AGD) index in male offspring decreased significantly in groups 1 and 2
      in comparison with groups 3 or 4. However, there was no significant difference in
      the AGD index between groups 3 and 4. At 90 days of age, the incidence of
      cryptorchidism was 55.3% in group 1 and 25.9% in group 2. In contrast, all testes
      descended into the scrotum in both groups 3 and 4. The incidence of
      cryptorchidism was significantly higher in group 1 than in groups 2 (P <.05), 3,
      or 4 (P <.01), while the incidence of cryptorchidism was also significantly
      higher in group 2 than in groups 3 or 4 (P <.01). The weight of the testis
      decreased significantly more in the undescended testis than in the scrotal testis
      (P <.01); however, there was no significant difference in the weight of the
      scrotal testes among the 4 groups. The histologic development of the undescended
      testes showed an absence of germ cells and smaller tubes in comparison with those
      of scrotal testes, which showed an advanced differentiation of germ cells and
      larger tubes in all 4 groups. CONCLUSIONS: These findings suggest that the
      antiandrogenic effect of cimetidine inhibits both the testicular descent and
      genital differentiation in fetuses and also causes cryptorchidism in postnatal
      rats. These same events might also occur in human fetuses when high doses of
      cimetidine are administered to pregnant women around the end of the first
      trimester.

PMID- 11821829
TI  - A randomized controlled trial comparing open vs laparoscopy-assisted distal
      gastrectomy for the treatment of early gastric cancer: an interim report.
AB  - BACKGROUND: The application of laparoscopy-assisted distal gastrectomy (LADG) for
      early gastric cancer remains controversial among gastric surgeons. The purpose of
      this study was to compare LADG with open distal gastrectomy (ODG) regarding
      clinical outcome and postoperative parameters, including postoperative pain and
      pulmonary function. METHODS: From October 1998 to March 2001, 28 patients with
      early gastric cancer were randomly assigned to an LADG (n = 14) or ODG group (n =
      14) with Billroth I reconstruction. Postoperative pain during resting, coughing,
      and walking were evaluated by a visual analog scale (VAS). Pulmonary functions
      such as forced vital capacity (FVC) and forced expiratory volume in 1 second
      (FEV1) measured on the third postoperative day were compared with preoperative
      functions. RESULTS: Patients in the 2 groups were comparable for age, gender,
      height, weight, staging, and location of gastric cancer. The mean blood loss was
      significantly less in the LADG than in the ODG group (P <.05). Histologic
      examinations of resected specimens revealed that these 2 operations were
      identical from the standpoint of curability. Patients in the LADG group recovered
      both bowel movement and walking ability earlier than did patients in the ODG
      group (P <.05). The postoperative VAS pain score during rest was lower for 3 days
      after LADG than ODG (P <.05) and for 1 day during coughing or walking (P <.05).
      The pulmonary functions such as FVC and FEV1 values were reduced on the third day
      after LADG and ODG. However, the FVC value on the third day after LADG was lower
      than after ODG (P <.05). CONCLUSIONS: This study demonstrates that LADG has
      several advantages including an earlier recovery, less pain, and less impaired
      pulmonary function after gastric surgery when compared with ODG; furthermore, no
      reduction in curability was observed.

PMID- 11821830
TI  - Minimally invasive hepatectomy: modulation of systemic reactions to operation or
      laparoscopic approach?
AB  - BACKGROUND: A new concept of surgical stress has been proposed that consists of
      both aggressiveness of operation and systemic reactions to an operation. METHODS
      AND RESULTS: We have investigated a possible modulation of such systemic
      reactions to operation and have demonstrated the following 3 points: (1)
      coagulation and fibrinolytic systems are independently activated during
      hepatectomy and such activation can be modulated by protease inhibitors such as
      nafamostat mesilate and antithrombin III; (2) elevated thromboxane A2 during
      hepatectomy is characterized in the prostanoid system, the elevation of
      thromboxane A2 is inhibited by thromboxane A2 synthetase inhibitor, and
      postoperative liver injury is reduced; (3) cytokine response induced by
      hepatectomy is modulated by preoperative administration of methylprednisolone,
      leading to possible prevention of bacterial translocation. Therefore, modulating
      systemic reactions to hepatectomy may be important for successful minimally
      invasive hepatectomy. Another important option for minimally invasive hepatectomy
      is the use of operative procedures such as laparoscope or thoracoscope. We have
      investigated the usefulness of a laparoscopic hepatectomy from the standpoints of
      early and long-term outcome after hepatectomy. Laparoscopic hepatectomy, which is
      a difficult and dangerous procedure, can be a feasible option and can result in
      better short-term outcome and a similar long-term outcome after hepatectomy when
      compared with conventional open hepatectomy. Therefore, the laparoscopic approach
      is also a viable option for minimally invasive hepatectomy. CONCLUSIONS:
      Modulation of systemic reactions to the operation itself and laparoscopic
      hepatectomy may be new strategies for performing minimally invasive hepatectomy.

PMID- 11821831
TI  - Laparoscopic splenectomy for hematologic diseases.
AB  - BACKGROUND: Laparoscopic splenectomy has been demonstrated to be technically
      feasible and safe for the treatment of hematologic diseases. METHODS: The study
      comprised 64 consecutive patients with chronic immune thrombocytopenia purpura
      (ITP) who were admitted to our hospital from 1992 to 2000 and underwent
      laparoscopic splenectomy. Forty-one consecutive patients with ITP who underwent
      open splenectomy performed at the same hospital by the same surgical team between
      1986 and 2000 were selected as the control group. RESULTS: We performed
      laparoscopic splenectomies for ITP, hereditary spherocytosis (HS), malignant
      lymphoma, autoimmune hemolytic anemia, and cryoglobulinemia. Laparoscopic surgery
      as compared with open surgery in ITP revealed a significantly lower pain
      medication requirement, an earlier resumption of oral intake, and a shorter
      hospital stay, but a longer operative time. During the present study (range: 3.8
      80 months), the cumulative rate of nonrecurrence was 67.9% at 5 years after
      surgery, which was similar to the rate for the previous open splenectomy.
      CONCLUSIONS: Laparoscopic splenectomy is considered to be a suitable alternative
      therapeutic modality in the treatment of hematologic diseases.

PMID- 11821832
TI  - Early results of an endoscope-assisted subcutaneous mastectomy and reconstruction
      for breast cancer.
AB  - BACKGROUND: Subcutaneous mastectomy and reconstruction (SMR) is well established;
      however, most incisions are made directly on the breast, and the majority of
      patients care about visible scars even if they are satisfied with the
      reconstructed breast. METHODS: From August 1998 to March 2001, a total of 46
      patients (including 2 bilateral cases) with breast cancer underwent SMR using a
      saline-filled prosthesis by lateral axillary incision. There were 25 patients who
      received previous SMR without endoscopic assistance (group A) and 21 patients who
      underwent an endoscope-assisted SMR (E-SMR) (group B). These 2 groups were
      compared for curability, morbidity, and cosmesis. RESULTS: The median follow-up
      period was 19.2 + 9.8 months (range, 5.8 - 35.2 months). No significant
      difference was found in clinicopathologic data between the 2 groups. The
      operation time was 176 minutes in group A and 237 minutes in group B, and the
      estimated blood loss was 189 mL vs 356 mL, respectively. No critical
      complications were seen in either group. The average length of incision was 10 cm
      in group A and 5.7 cm in group B. As for the patients' satisfaction, the
      incidence of "excellent" plus "good" ratings was 76% in group A and 90.4% in
      group B. CONCLUSIONS: E-SMR is a new option that can provide an improved
      operative view and better cosmetic results for the treatment of breast cancer
      than with SMR. The operation time is longer than for SMR, but the incision is
      drastically shorter, resulting in better cosmesis and increased patient
      satisfaction.

PMID- 11821833
TI  - A new era of robotic surgery assisted by a computer-enhanced surgical system.
AB  - Computer-enhanced robotic surgery has now been introduced into general surgical
      practice. The robotic system enables us to manipulate endoscopic instruments, as
      well as instruments during open surgical intervention, regarding both the
      operative field and operation techniques. This technologic innovation should
      therefore help surgeons overcome various difficulties and allow them to perform
      more precise, safer, and more minimally invasive surgery in the coming era.

PMID- 11821834
TI  - Hybrid-artificial liver support system.
AB  - We originally developed a multi-capillary polyurethane foam packed-bed module as
      a hybrid-artificial liver support system (HALSS) and have applied for the
      permission of the clinical application to our institutional ethical committee. We
      summarized here the history, recent obstacles in clinical applications, and
      future prospects of HALSS, including our own.

PMID- 11821835
TI  - The medical care system in Japan.

PMID- 11821836
TI  - Hunted down and hounded out.

PMID- 11821837
TI  - Nothing succeeds like failure.

PMID- 11821838
TI  - "Festo" manifesto heard before US Supreme Court.

PMID- 11821839
TI  - CGIAR under pressure to support seed treaty.

PMID- 11821840
TI  - Amgen's big-ticket play for Immunex.

PMID- 11821841
TI  - Maize uncertainties create political fallout.

PMID- 11821842
TI  - EC prepares strategic vision for biotechnology.

PMID- 11821843
TI  - Genentech awarded critical antibody patent.

PMID- 11821844
TI  - Xenotransplantation success for Immerge.

PMID- 11821845
TI  - The perils of federalizing vaccine production.

PMID- 11821846
TI  - Antibodies for defense against biological attack.

PMID- 11821848
TI  - Transparency in public relations.

PMID- 11821849
TI  - Pinpointing anthrax-toxin inhibitors.

PMID- 11821850
TI  - Rethinking substantial equivalence.

PMID- 11821851
TI  - ES cell media.

PMID- 11821852
TI  - Antisense and sensibility.

PMID- 11821853
TI  - A stimulating presentation.

PMID- 11821854
TI  - Binding assays get into the groove.

PMID- 11821855
TI  - Protein domain networking.

PMID- 11821856
TI  - Inter-kingdom DNA transfer decoded.

PMID- 11821858
TI  - Engineering polydactyl zinc-finger transcription factors.
AB  - The availability of rapid and robust methods for controlling gene function is of
      prime importance not only for assigning functions to newly discovered genes, but
      also for therapeutic intervention. Traditionally, gene function has been probed
      by often-laborious methods that either increase the level of a gene product or
      decrease it. Advances now make it possible to rapidly produce zinc-finger
      proteins capable of recognizing virtually any 18 bp stretch of DNA--a sequence
      long enough to specify a unique address in any genome. The attachment of
      functional domains also allows the design of tailor-made transcription factors
      for specific genes. Recent studies demonstrate that artificial transcription
      factors are capable of controlling the expression of endogenous genes in their
      native chromosomal context with a high degree of specificity in both animals and
      plants. Dominant regulatory control of expression of any endogenous gene can be
      achieved rapidly and can be also placed under chemical control. A wide range of
      potential applications is now within reach.

PMID- 11821860
TI  - Enhancement of antitumor immunity by prolonging antigen presentation on dendritic
      cells.
AB  - Vaccination with dendritic cells (DCs) pulsed with antigenic peptides derived
      from various tumor antigens has great, but as yet significantly unrealized,
      potential in cancer treatment. Here, we describe a strategy for prolonged
      presentation of an MHC class I-restricted self-peptide on DCs through linkage of
      it to a cell penetrating peptide (CPP). DCs loaded with a peptide derived from
      tyrosinase-related protein 2 (TRP2) covalently linked to a CPP1 sequence retained
      full capacity to stimulate T cells for at least 24 h, completely protected
      immunized mice from subsequent tumor challenge, and significantly inhibited lung
      metastases in a 3-day tumor model. DCs pulsed with TRP2 alone failed to provide
      any of these protections. In addition, we demonstrate that both CD4+ and CD8+ T
      cells were required for potent antitumor immunity. This CPP-based approach may be
      generally applicable to enhance the efficacy of DC-based peptide vaccines against
      cancer and other diseases.

PMID- 11821859
TI  - Ex vivo expansion of polyclonal and antigen-specific cytotoxic T lymphocytes by
      artificial APCs expressing ligands for the T-cell receptor, CD28 and 4-1BB.
AB  - The ex vivo priming and expansion of human cytotoxic T lymphocytes (CTLs) has
      potential for use in immunotherapy applications for cancer and infectious
      diseases. To overcome the difficulty in obtaining sufficient numbers of CTLs, we
      have developed artificial antigen-presenting cells (aAPCs) expressing ligands for
      the T-cell receptor (TCR) and the CD28 and 4-1BB co-stimulatory surface
      molecules. These aAPCs reproducibly activate and rapidly expand polyclonal or
      antigen-specific CD8(+) T cells. The starting repertoire of CD8+ T cells was
      preserved during culture. Furthermore, apoptosis of cultured CD8(+) T cells was
      diminished by this approach. This approach may have important therapeutic
      implications for adoptive immunotherapy.

PMID- 11821861
TI  - Simultaneous measurement of multiple active kinase states using polychromatic
      flow cytometry.
AB  - Intracellular assays of signaling systems have been limited by an inability to
      correlate functional subsets of cells in complex populations on the basis of
      active kinase states. Such correlations could be important in distinguishing
      changes in signaling status that arise in rare cell subsets during functional
      activation or in disease manifestation. Here we demonstrate the ability to
      simultaneously detect activated kinase members of the mitogen-activated protein
      kinases family (p38 MAPK, p44/42 MAPK, JNK/SAPK), members of cell survival
      pathways (AKT/PKB), and members of T-cell activation pathways (TYK2), among
      others, in subpopulations of complex cell populations by multiparameter flow
      cytometric analysis. We demonstrate the utility of these probes in identifying
      distinct signaling cascades for (1) both artificial and physiological stimulatory
      conditions of peripheral blood mononuclear cells (PBMCs), (2) cytokine
      stimulation in human memory and naive lymphocyte subsets as identified by five
      differentiation markers, and (3) ordering of kinase activation in potential
      signaling hierarchies. Polychromatic flow-cytometric active kinase measurements
      demonstrate that multidimensional analysis of signaling pathways can provide
      functional signaling pathway assessment on a single-cell level and allow for
      potential correlation with biological and clinical parameters.

PMID- 11821862
TI  - De novo peptide sequencing and quantitative profiling of complex protein mixtures
      using mass-coded abundance tagging.
AB  - Proteomic studies require efficient, robust, and practical methods of
      characterizing proteins present in biological samples. Here we describe an
      integrated strategy for systematic proteome analysis based on differential
      guanidination of C-terminal lysine residues on tryptic peptides followed by
      capillary liquid chromatography-electrospray tandem mass spectrometry. The
      approach, termed mass-coded abundance tagging (MCAT), facilitates the automated,
      large-scale, and comprehensive de novo determination of peptide sequence and
      relative quantitation of proteins in biological samples in a single analysis.
      MCAT offers marked advantages as compared with previously described methods and
      is simple, economic, and effective when applied to complex proteomic mixtures.
      MCAT is used to identify proteins, including polymorphic variants, from complex
      mixtures and measure variation in protein levels from diverse cell types.

PMID- 11821863
TI  - Molecular beacons for detecting DNA binding proteins.
AB  - We report here a simple, rapid, homogeneous fluorescence assay, the molecular
      beacon assay, for the detection and quantification of sequence-specific DNA
      binding proteins. The central feature of the assay is the protein-dependent
      association of two DNA fragments each containing about half of a DNA sequence
      defining a protein-binding site. Protein-dependent association of DNA fragments
      can be detected by any proximity-based spectroscopic signal, such as fluorescence
      resonance energy transfer (FRET) between fluorochromes introduced into these DNA
      molecules. The assay is fully homogeneous and requires no manipulations aside
      from mixing of the sample and the test solution. It offers flexibility with
      respect to the mode of signal detection and the fluorescence probe, and is
      compatible with multicolor simultaneous detection of several proteins. The assay
      can be used in research and medical diagnosis and for high-throughput screening
      of drugs targeted to DNA-binding proteins.

PMID- 11821865
TI  - High-resolution footprinting of sequence-specific protein-DNA contacts.
AB  - Gene transcription is regulated by proteins that bind specific DNA sequences and
      control the initiation of RNA synthesis. A major challenge is to map all of the
      regulatory sites in the genome and to identify the proteins that bind them.
      Because members of transcription factor families often exhibit similar sequence
      preferences, methods for determining intermolecular contacts in protein-DNA
      interfaces must be sensitive to even subtle structural differences. The most
      detailed structural views of protein-DNA interfaces have been obtained through X
      ray crystallography and NMR spectroscopy, and these methods have revolutionized
      the understanding of the structural determinants of sequence-specific
      recognition. Neither crystallography nor NMR, however, is particularly well
      suited to high-throughput applications such as pan-genomic elucidation of
      regulatory sequences; in addition, these methods yield no information on the
      energetic contribution of particular contacts. Here we report a straightforward,
      high-resolution biochemical method for mapping, at single-nucleotide resolution,
      DNA bases that are subject to sequence-specific contacts by regulatory proteins.

PMID- 11821864
TI  - An unnatural base pair for incorporating amino acid analogs into proteins.
AB  - An unnatural base pair of 2-amino-6-(2-thienyl)purine (denoted by s) and pyridin
      2-one (denoted by y) was developed to expand the genetic code. The ribonucleoside
      triphosphate of y was site-specifically incorporated into RNA, opposite s in a
      template, by T7 RNA polymerase. This transcription was coupled with translation
      in an Escherichia coli cell-free system. The yAG codon in the transcribed ras
      mRNA was recognized by the CUs anticodon of a yeast tyrosine transfer RNA (tRNA)
      variant, which had been enzymatically aminoacylated with an unnatural amino acid,
      3-chlorotyrosine. Site-specific incorporation of 3-chlorotyrosine into the Ras
      protein was demonstrated by liquid chromatography-mass spectrometry (LC-MS)
      analysis of the products. This coupled transcription-translation system will
      permit the efficient synthesis of proteins with a tyrosine analog at the desired
      position.

PMID- 11821866
TI  - Detection of tumor mutations in the presence of excess amounts of normal DNA.
AB  - Mutations are important markers in the early detection of cancer. Clinical
      specimens such as bodily fluid samples often contain a small percentage of
      mutated cells in a large background of normal cells. Thus, assays to detect
      mutations leading to cancer need to be highly sensitive and specific. In
      addition, they should be possible to carry out in an automated and high
      throughput manner to allow large-scale screening. Here we describe a screening
      method, termed PPEM (PNA-directed PCR, primer extension, MALDI-TOF), that
      addresses these needs more effectively than do existing methods. DNA samples are
      first amplified using peptide nucleic acid (PNA)-directed PCR clamping reactions
      in which mutated DNA is preferentially enriched. The PCR-amplified DNA fragments
      are then sequenced through primer extension to generate diagnostic products.
      Finally, mutations are identified using matrix-assisted laser
      desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. This method
      can detect as few as 3 copies of mutant alleles in the presence of a 10,000-fold
      excess of normal alleles in a robust and specific manner. In addition, the method
      can be adapted for simultaneous detection of multiple mutations and is amenable
      to high-throughput automation.

PMID- 11821867
TI  - Defensive use of publications in an intellectual property strategy.

PMID- 11821871
TI  - Succession planning: putting an organization's knowledge to work.

PMID- 11821872
TI  - Health and wealth.

PMID- 11821873
TI  - Metabolism of PGE2 by prostaglandin dehydrogenase is essential for remodeling the
      ductus arteriosus.

PMID- 11821874
TI  - RAE reveals drastic improvement in UK research.

PMID- 11821875
TI  - Drug R&D costs queried.

PMID- 11821876
TI  - Edible vaccines: not quite ready for prime time.

PMID- 11821877
TI  - MMP inhibitors: glimmers of hope amidst clinical failures.

PMID- 11821878
TI  - Global research fund proposed.

PMID- 11821881
TI  - Controversial allocation rules for liver transplants.

PMID- 11821882
TI  - Salvador Moncada.

PMID- 11821883
TI  - Research governance at the crossroads.

PMID- 11821886
TI  - Rewiring the Parkinsonian brain.

PMID- 11821887
TI  - Stemming the tide of rejection.

PMID- 11821888
TI  - An essential link to mammary cancer?

PMID- 11821889
TI  - From CSD to headache: a long and winding road.

PMID- 11821890
TI  - A new piece in the diabetes puzzle.

PMID- 11821891
TI  - Mucosal gatekeepers: selecting HIV viruses for early infection.

PMID- 11821892
TI  - Zip codes: deciphering vascular addresses.

PMID- 11821893
TI  - New avenues for anti-inflammatory therapy.

PMID- 11821895
TI  - Steps toward mapping the human vasculature by phage display.
AB  - The molecular diversity of receptors in human blood vessels remains largely
      unexplored. We developed a selection method in which peptides that home to
      specific vascular beds are identified after administration of a peptide library.
      Here we report the first in vivo screening of a peptide library in a patient. We
      surveyed 47,160 motifs that localized to different organs. This large-scale
      screening indicates that the tissue distribution of circulating peptides is
      nonrandom. High-throughput analysis of the motifs revealed similarities to
      ligands for differentially expressed cell-surface proteins, and a candidate
      ligand-receptor pair was validated. These data represent a step toward the
      construction of a molecular map of human vasculature and may have broad
      implications for the development of targeted therapies.

PMID- 11821896
TI  - Rapamycin inhibits primary and metastatic tumor growth by antiangiogenesis:
      involvement of vascular endothelial growth factor.
AB  - Conventional immunosuppressive drugs have been used effectively to prevent
      immunologic rejection in organ transplantation. Individuals taking these drugs
      are at risk, however, for the development and recurrence of cancer. In the
      present study we show that the new immunosuppressive drug rapamycin (RAPA) may
      reduce the risk of cancer development while simultaneously providing effective
      immunosuppression. Experimentally, RAPA inhibited metastatic tumor growth and
      angiogenesis in in vivo mouse models. In addition, normal immunosuppressive doses
      of RAPA effectively controlled the growth of established tumors. In contrast, the
      most widely recognized immunosuppressive drug, cyclosporine, promoted tumor
      growth. From a mechanistic perspective, RAPA showed antiangiogenic activities
      linked to a decrease in production of vascular endothelial growth factor (VEGF)
      and to a markedly inhibited response of vascular endothelial cells to stimulation
      by VEGF. Thus, the use of RAPA, instead of cyclosporine, may reduce the chance of
      recurrent or de novo cancer in high-risk transplant patients.

PMID- 11821897
TI  - Intrinsic brain activity triggers trigeminal meningeal afferents in a migraine
      model.
AB  - Although the trigeminal nerve innervates the meninges and participates in the
      genesis of migraine headaches, triggering mechanisms remain controversial and
      poorly understood. Here we establish a link between migraine aura and headache by
      demonstrating that cortical spreading depression, implicated in migraine visual
      aura, activates trigeminovascular afferents and evokes a series of cortical
      meningeal and brainstem events consistent with the development of headache.
      Cortical spreading depression caused long-lasting blood-flow enhancement
      selectively within the middle meningeal artery dependent upon trigeminal and
      parasympathetic activation, and plasma protein leakage within the dura mater in
      part by a neurokinin-1-receptor mechanism. Our findings provide a neural
      mechanism by which extracerebral cephalic blood flow couples to brain events;
      this mechanism explains vasodilation during headache and links intense
      neurometabolic brain activity with the transmission of headache pain by the
      trigeminal nerve.

PMID- 11821898
TI  - Prolonged survival and decreased abnormal movements in transgenic model of
      Huntington disease, with administration of the transglutaminase inhibitor
      cystamine.
AB  - An expanded polyglutamine domain in huntingtin underlies the pathogenic events in
      Huntington disease (HD), characterized by chorea, dementia and severe weight
      loss, culminating in death. Transglutaminase (TGase) may be critical in the
      pathogenesis, via cross-linking huntingtin. Administration of the TGase
      competitive inhibitor, cystamine, to transgenic mice expressing exon 1 of
      huntingtin containing an expanded polyglutamine repeat, altered the course of
      their HD-like disease. Cystamine given intraperitoneally entered brain where it
      inhibited TGase activity. When treatment began after the appearance of abnormal
      movements, cystamine extended survival, reduced associated tremor and abnormal
      movements and ameliorated weight loss. Treatment did not influence the appearance
      or frequency of neuronal nuclear inclusions. Unexpectedly, cystamine treatment
      increased transcription of one of the two genes shown to be neuroprotective for
      polyglutamine toxicity in Drosophila, dnaj (also known as HDJ1 and Hsp40 in
      humans and mice, respectively). Inhibition of TGase provides a new treatment
      strategy for HD and other polyglutamine diseases.

PMID- 11821899
TI  - Primary intestinal epithelial cells selectively transfer R5 HIV-1 to CCR5+ cells.
AB  - The upper gastrointestinal tract is a principal route of HIV-1 entry in vertical
      transmission and after oral-genital contact. The phenotype of the newly acquired
      virus is predominantly R5 (CCR5-tropic) and not X4 (CXCR4-tropic), although both
      R5 and X4 viruses are frequently inoculated onto the mucosa. Here we show that
      primary intestinal (jejunal) epithelial cells express galactosylceramide, an
      alternative primary receptor for HIV-1, and CCR5 but not CXCR4. Moreover, we show
      that intestinal epithelial cells transfer R5, but not X4, viruses to CCR5+
      indicator cells, which can efficiently replicate and amplify virus expression.
      Transfer was remarkably efficient and was not inhibited by the fusion blocker T
      20, but was substantially reduced by colchicine and low (4 degrees C)
      temperature, suggesting endocytotic uptake and microtubule-dependent transcytosis
      of HIV-1. Our finding that CCR5+ intestinal epithelial cells select and transfer
      exclusively R5 viruses indicates a mechanism for the selective transmission of R5
      HIV-1 in primary infection acquired through the upper gastrointestinal tract.

PMID- 11821900
TI  - CCL27-CCR10 interactions regulate T cell-mediated skin inflammation.
AB  - The skin-associated chemokine CCL27 (also called CTACK, ALP and ESkine) and its
      receptor CCR10 (GPR-2) mediate chemotactic responses of skin-homing T cells in
      vitro. Here we report that most skin-infiltrating lymphocytes in patients
      suffering from psoriasis, atopic or allergic-contact dermatitis express CCR10.
      Epidermal basal keratinocytes produced CCL27 protein that bound to extracellular
      matrix, mediated adhesion and was displayed on the surface of dermal endothelial
      cells. Tumor necrosis factor-alpha and interleukin-1beta induced CCL27 production
      whereas the glucocorticosteroid clobetasol propionate suppressed it. Circulating
      skin-homing CLA+ T cells, dermal microvascular endothelial cells and fibroblasts
      expressed CCR10 on their cell surface. In vivo, intracutaneous CCL27 injection
      attracted lymphocytes and, conversely, neutralization of CCL27-CCR10 interactions
      impaired lymphocyte recruitment to the skin leading to the suppression of
      allergen-induced skin inflammation. Together, these findings indicate that CCL27
      CCR10 interactions have a pivotal role in T cell-mediated skin inflammation.

PMID- 11821901
TI  - IL-4-secreting CD4+ T cells are crucial to the development of CD8+ T-cell
      responses against malaria liver stages.
AB  - CD4+ T cells are crucial to the development of CD8+ T cell responses against
      hepatocytes infected with malaria parasites. In the absence of CD4+ T cells, CD8+
      T cells initiate a seemingly normal differentiation and proliferation during the
      first few days after immunization. However, this response fails to develop
      further and is reduced by more than 90%, compared to that observed in the
      presence of CD4+ T cells. We report here that interleukin-4 (IL-4) secreted by
      CD4+ T cells is essential to the full development of this CD8+ T cell response.
      This is the first demonstration that IL-4 is a mediator of CD4/CD8 cross-talk
      leading to the development of immunity against an infectious pathogen.

PMID- 11821902
TI  - Preimplantation-stage stem cells induce long-term allogeneic graft acceptance
      without supplementary host conditioning.
AB  - Hematopoietic stem cells have been successfully employed for tolerance induction
      in a variety of rodent and large animal studies. However, clinical
      transplantation of fully allogeneic bone marrow or blood-borne stem cells is
      still associated with major obstacles, such as graft-versus-host disease or
      cytoreductive conditioning-related toxicity. Here we show that when rat embryonic
      stem cell-like cells of WKY origin are injected intraportally into fully MHC
      mismatched DA rats, they engraft permanently (>150 days) without supplementary
      host conditioning. This deviation of a potentially alloreactive immune response
      sets the basis for long-term graft acceptance of second-set transplanted WKY
      cardiac allografts. Graft survival was strictly correlated with a state of mixed
      chimerism, which required functional thymic host competence. Our results provide
      a rationale for using preimplantation-stage stem cells as vehicles in gene
      therapy and for the induction of long-term graft acceptance.

PMID- 11821903
TI  - Small molecule insulin mimetics reduce food intake and body weight and prevent
      development of obesity.
AB  - Obesity and insulin resistance are major risk factors for a number of metabolic
      disorders, such as type 2 diabetes mellitus. Insulin has been suggested to
      function as one of the adiposity signals to the brain for modulation of energy
      balance. Administration of insulin into the brain reduces food intake and body
      weight, and mice with a genetic deletion of neuronal insulin receptors are
      hyperphagic and obese. However, insulin is also an anabolic factor; when
      administered systemically, pharmacological levels of insulin are associated with
      body weight gain in patients. In this study, we investigated the efficacy and
      feasibility of small molecule insulin mimetic compounds to regulate key
      parameters of energy homeostasis. Central intracerebroventricular (i.c.v.)
      administration of an insulin mimetic resulted in a dose-dependent reduction of
      food intake and body weight in rats, and altered the expression of hypothalamic
      genes known to regulate food intake and body weight. Oral administration of a
      mimetic in a mouse model of high-fat diet-induced obesity reduced body weight
      gain, adiposity and insulin resistance. Thus, insulin mimetics have a unique
      advantage over insulin in the control of body weight and hold potential as a
      novel anti-obesity treatment.

PMID- 11821904
TI  - Visualization and quantification of T cell-mediated cytotoxicity using cell
      permeable fluorogenic caspase substrates.
AB  - We have developed a non-radioactive flow-cytometry assay to monitor and quantify
      the target-cell killing activities mediated by cytotoxic T lymphocytes (CTLs).
      This flow-cytometry CTL (FCC) assay is predicated on measurement of CTL-induced
      caspase activation in target cells through detection of the specific cleavage of
      fluorogenic caspase substrates. Here we show that this assay reliably detects
      antigen-specific CTL killing of target cells, and demonstrate that it provides a
      more sensitive, more informative and safer alternative to the standard 51Cr
      release assay most often used to quantify CTL responses. The FCC assay can be
      used to study CTL-mediated killing of primary host target cells of different cell
      lineages, and enables the study of antigen-specific cellular immune responses in
      real time at the single-cell level. As such, the FCC assay can provide a valuable
      tool for studies of infectious disease pathogenesis and development of new
      vaccines and immunotherapies.

PMID- 11821906
TI  - First Zuckerkandl Prize awarded.

PMID- 11821907
TI  - Zuckerkandl Prize.

PMID- 11821908
TI  - Lineage specificity of the evolutionary dynamics of the mtDNA D-loop region in
      rodents.
AB  - This paper reports an intraorder study on the D-loop-containing region of the
      mitochondrial DNA in rodents. A complete multialignment of this region is not
      feasible with the exception of some conserved regions. The comparative analysis
      of 25 complete rodent sequences from 23 species plus one lagomorph has revealed
      that only the central domain (CD), a conserved region of about 80 bp in the
      extended termination-associated sequences (ETAS) domain, adjacent to the CD, the
      ETAS1, and conserved sequence block (CSB) 1 blocks are present in all rodent
      species, whereas the presence of CSB2 and CSB3 is erratic within the order. We
      have also found a conserved region of 90 bp located between tRNAPro and ETAS1
      present in fat dormouse, squirrel, guinea pig, and rabbit. Repeated sequences are
      present in both the ETAS and the CSB domain, but the repeats differ in length,
      copy number, and base composition in different species. The potential use of the
      D-loop for evolutionary studies has been investigated; the presence/absence of
      conserved blocks and/or repeated sequences cannot be used as a reliable
      phylogenetic marker, since in some cases they may be shared by distantly related
      organisms but not by close ones, while in other ones a relationship between tree
      topology and presence/absence of such motifs is observed. Better results can be
      obtained by the use of the CD, which, however, due to its reduced size, when used
      for tracing a phylogenetic tree, shows some nodes with low statistical support.

PMID- 11821909
TI  - Rates of molecular evolution in RNA viruses: a quantitative phylogenetic
      analysis.
AB  - The study of rates of nucleotide substitution in RNA viruses is central to our
      understanding of their evolution. Herein we report a comprehensive analysis of
      substitution rates in 50 RNA viruses using a recently developed maximum
      likelihood phylogenetic method. This analysis revealed a significant relationship
      between genetic divergence and isolation time for an extensive array of RNA
      viruses, although more rate variation was usually present among lineages than
      would be expected under the constraints of a molecular clock. Despite the lack of
      a molecular clock, the range of statistically significant variation in overall
      substitution rates was surprisingly narrow for those viruses where a significant
      relationship between genetic divergence and time was found, as was the case when
      synonymous sites were considered alone, where the molecular clock was rejected
      less frequently. An analysis of the ecological and genetic factors that might
      explain this rate variation revealed some evidence of significantly lower
      substitution rates in vector-borne viruses, as well as a weak correlation between
      rate and genome length. Finally, a simulation study revealed that our maximum
      likelihood estimates of substitution rates are valid, even if the molecular clock
      is rejected, provided that sufficiently large data sets are analyzed.

PMID- 11821910
TI  - Comparative structure analysis of vertebrate U17 small nucleolar RNA (snoRNA).
AB  - Intron-encoded U17 RNA is a member of the H/ACA box class of small nucleolar RNAs
      (snoRNAs) involved in ribosomal RNA (rRNA) maturation. U17 snoRNA shows typical
      characteristics of guide RNAs, which specify sites of pseudouridylation on the
      precursor rRNA (pre-rRNA). However, in spite of the presence of H and ACA boxes
      and short regions complementary to the pre-rRNA, its secondary structure does not
      show any evident pseudouridylation pocket. Moreover, its length is larger than
      the typical one of snoRNAs and it shows a more complex secondary structure
      compared to the canonical hairpin-hinge-hairpin-tail architecture. Greater
      knowledge of eukaryotic U17 snoRNA structure is needed to understand its precise
      function. Comparative molecular studies of this snoRNA with different vertebrates
      is still limited to a few cases. With the aim of increasing our understanding of
      the U17 snoRNA secondary structure, we cloned the U17 snoRNA coding sequence from
      10 additional vertebrate taxa. On the basis of structure homology derived from
      sequence comparison and thermodynamic prediction, we propose a vertebrate
      consensus secondary structure and novel conserved sequence boxes for U17 snoRNA.
      Host gene localization of U17 coding sequence and its ability to serve as a guide
      sequence for RNA/RNA interaction has been evolutionarily traced from fish to
      mammals. It is interesting to note that turtle U17 snoRNAs show a noncanonical
      ACA box, mainly consisting in the GCA box. Microinjections in X. laevis oocytes
      of in vitro synthesized turtle transcripts containing the U17 RNA sequence which
      have canonical ACA, wild-type GCA, and mutated CCA and UCA boxes resulted in
      efficient production of mature U17 snoRNA.

PMID- 11821911
TI  - In vitro selection of a deoxyribozyme that can utilize multiple substrates.
AB  - Deoxyribozymes that could catalyze the formation of an internucleotide
      phosphorothioester linkage were selected from a random sequence pool. During the
      course of the selection, the pool was successively challenged with five
      oligonucleotide substrates, each of which terminated in the same hexanucleotide
      sequence. Selected deoxyribozyme ligases could use all five substrates, albeit to
      different degrees, and appeared to form secondary structures that allow
      differential pairing between the deoxyribozyme and each substrate. These results
      suggest that early replicases may have been able to bind a variety of
      oligonucleotide substrates while catalyzing ligation via a common junction.

PMID- 11821912
TI  - Stretch coding and block coding: two new strategies to represent questionably
      aligned DNA sequences.
AB  - Most coding strategies that address the problem of questionable alignment
      (elision, case sensitive, missing, polymorphic, gaps as presence/absence matrix)
      conflict with phylogenetic principles, particularly those relating to the concept
      of homology (shared similiarity explained by common ancestry). In some cases, the
      test of conjunction is failed. In other cases, characters that are coded
      ambiguously can lead to character-state optimization in the terminal taxa that
      conflicts with the original observations. Only data exclusion and contraction
      avoid these pitfalls. In highly dissimilar sequences additional character states
      can represent the available information. Two new methods that accomplish this
      block and stretch coding-are introduced here. These two new coding strategies are
      not in conflict with the test of conjunction and do not contradict the original
      observations. They are comparable to coding practices with morphological data
      once the intrinsic differences due to character-state identity and topographical
      identity have been taken into account. It is suggested that, of the three
      recoding methods, the one is selected that preserves the maximum potential
      phylogenetic information as measured with the minimum number of steps required
      for the particular part of the data matrix.

PMID- 11821913
TI  - Bootstrap confidence levels for HIV-1 recombination.
AB  - Recombination has been invoked to explain the disparate evolutionary
      relationships observed for different genes or sequence segments of a single HIV-1
      genome. We present a new method of assessing confidence in HIV-1 recombination as
      an alternative to the segment-by-segment nonparametric bootstrap commonly applied
      to confirm HIV-1 recombinant data. Our new method uses the bias-corrected
      accelerated percentile interval (BCa) bootstrap method as applied to the "problem
      of regions" (Efron and Tibshirani 1998). It is an extension of the BCa method
      used in the inference of evolutionary relationships (Efron et al. 1996). This
      method has two advantages over the traditional bootstrap procedure: (1) it gives
      a single overall confidence measure rather than segment-by-segment results, and
      (2) it is more accurate. We test our method on 61 sequences, including 16 with
      ambiguous recombinant status.

PMID- 11821914
TI  - Simultaneous molecular and morphological analysis of braconid relationships
      (Insecta: Hymenoptera: Braconidae) indicates independent mt-tRNA gene inversions
      within a single wasp family.
AB  - We investigated the phylogeny of the Braconidae (Insecta: Hymenoptera) with a
      much expanded data set compared with that of previous attempts, employing 16S and
      28S rDNA gene fragments, together with a suite of morphological characters, from
      74 ingroup taxa. Most notably, parsimony analyses under a range of models
      recovered the Aphidiinae as sister group to the cyclostomes and the Ichneutinae
      as sister group to the microgastroids. The cyclostomes were recovered as a
      natural group only if certain, putatively misplaced genera (Mesostoa,
      Aspilodemon) were excluded from them. Further, mapping of rearrangement
      characters onto this phylogeny of the Braconidae indicated parallel inversions of
      the mt-tRNAD gene, with the two instances of inversion distinguishable by the
      presence or absence of an additional tRNA gene (tRNAH). This is the first report
      of a parallel inversion of a mt-tRNA gene and makes the Braconidae the first
      metazoan family to display both parallel inversions and translocations.

PMID- 11821915
TI  - Do deletions of Mos1-like elements occur randomly in the Drosophilidae family?
AB  - We compared deleted copies of the seven mauritiana subfamilies of mariner
      transposable elements in species of the Drosophilidae. All elements were detected
      by PCR using the inverted terminal repeats of the Mos1 element of Drosophila
      mauritiana as primers. A higher frequency of breakpoints in the 5prime prime or
      minute part of the element compared to the 3prime prime or minute part was
      observed. Of the 27 deletions, 9 (33%) occurred between short direct repeats
      (SDR) of 5 to 8 bp. The SDRs can be at or close to the breakpoints of the
      deletion. A deleted copy of D. simulans (St. Martin population) had three repeats
      of a motif present only once in the complete consensus sequence. The high
      frequency of SDRs at or near the breakpoints of the deletions strongly suggests
      that some of them do not occur at random. Mechanisms that might explain these
      deletions, such as unequal crossing-over, ectopic recombination, and abortive gap
      repair, are discussed.

PMID- 11821916
TI  - Evolution of duplicated reggie genes in zebrafish and goldfish.
AB  - Invertebrates, tetrapod vertebrates, and fish might be expected to differ in
      their number of gene copies, possibly due the occurrence of genome duplication
      events during animal evolution. Reggie (flotillin) genes code for membrane
      associated proteins involved in growth signaling in developing and regenerating
      axons. Until now, there appeared to be only two reggie genes in fruitflies,
      mammals, and fish. The aim of this research was to search for additional copies
      of reggie genes in fishes, since a genome duplication might have increased the
      gene copy number in this group. We report the presence of up to four distinct
      reggie genes (two reggie-1 and two reggie-2 genes) in the genomes of zebrafish
      and goldfish. Phylogenetic analyses show that the zebrafish and goldfish sequence
      pairs are orthologous, and that the additional copies could have arisen through a
      genome duplication in a common ancestor of bony fish. The presence of novel
      reggie mRNAs in fish embryos indicates that the newly discovered gene copies are
      transcribed and possibly expressed in the developing and regenerating nervous
      system. The intron/exon boundaries of the new fish genes characterized here
      correspond with those of human genes, both in location and phase. An evolutionary
      scenario for the evolution of reggie intron-exon structure, where loss of introns
      appears to be a distinctive trait in invertebrate reggie genes, is presented.

PMID- 11821917
TI  - Exploring the phylogenetic utility of ITS sequences for animals: a test case for
      abalone (Haliotis).
AB  - To evaluate the general utility of sequences of the nuclear rDNA internal
      transcribed spacer (ITS) regions for phylogenetic analyses of animal species
      groups and their broader relationships, sequences were obtained for 19 species of
      the genus Haliotis plus a keyhole limpet and a more distantly related gastropod,
      the Chilean abalone. Three subclades of Haliotis species appear consistently,
      each encompassing little variation. They are (A) the North Pacific species, (B)
      the European species, and (C) the Australia species. The one Caribbean species
      examined clearly groups with the North Pacific clade, not the European clade. H.
      midae (South Africa) and H. diversicolor supertexta (Taiwan) both diverge basal
      to the European and Australian species groups in the phylogenetic trees. Sequence
      comparisons showed that one species of Haliotis, H. iris from New Zealand, is
      quite distant from the remaining Haliotis species, almost as much as the more
      obvious outgroup, the keyhole limpet, an observation common to other DNA sequence
      analyses of these taxa. Using the rate of nucleotide change calculated from the
      sister Caribbean-Pacific pair, the length of the H. iris long branch is
      compatible with the suggestion that its ancestry became isolated on New Zealand
      at Gondwandan breakup. Use of ITS permits a totally independent estimate of the
      phylogenetic relationships, yet branching order was very similar to that
      established using other DNA regions studied previously, including those under
      strong positive selection. Knowledge of the RNA transcript secondary structure is
      particularly useful in the optimal alignment of more distantly related taxa. The
      RNA transcript secondary structure of Haliotis ITS2 shows conservation of
      features found also in ITS2 of angiosperms and algal taxa. Since ITS,
      particularly ITS2, is not saturated with nucleotide changes even at the family
      level, it should be useful for phylogenetic reconstruction of animal groups, not
      just at the species and genus levels but perhaps also for families and above.

PMID- 11821918
TI  - On the occurrence of horizontal gene transfer among an arbitrarily chosen group
      of 26 genes.
AB  - The deduced amino acid sequences from 1200 Haemophilus influenzae genes was
      compared to a data set that contained the orfs from yeast, two different Archaea
      and the Gram+ and Gramminus sign bacteria, Bacillus subtilis and Escherichia
      coli. The results of the comparison yielded a 26 orthologous gene set that had at
      least one representative from each of the four groups. A four taxa phylogenetic
      relationship for these 26 genes was determined. The statistical significance of
      each minimal tree was tested against the two alternative four taxa trees. The
      result was that four genes significantly supported the (Archaea, Eukaryota)
      (Gram+, Gramminus sign) topology, two genes supported the one where Gramminus
      sign and Eukaryota form a clade, and one gene supported the tree where Gram+ and
      Eukaryota define one clade. The remaining genes do not uniquely support any
      phylogeny, thereby collapsing the two central nodes into a single node. These are
      referred to as star phylogenies. I offer a new suggestion for the mechanism that
      gave rise to the star phylogenies. Namely, these are genes that are younger than
      the underlying lineages that currently harbor them. This hypothesis is examined
      with two proteins that display the star phylogeny; namely onithine
      transcarbamylase and tryptophan synthetase. It is shown, using the distance
      matrix rate test, that the rate of evolution of these two proteins is comparable
      to a control gene when rates are determined by comparing closely related species.
      This implies that the genes under comparison experience comparable functional
      constraint. However, when the genes from remotely related species are compared, a
      plateau is encountered. Since we see no unusual levels of functional constraint
      this plateau cannot be attributed to the divergence of the protein having reached
      saturation. The simplest explanation is that the genes displaying the star
      phylogenies were introduced after Archaea, Eukaryota, and Bacteria had diverged
      from one another. They presumably spread through life by horizontal gene
      transfer.

PMID- 11821919
TI  - Evolution of the PP2C family in Caenorhabditis: rapid divergence of the sex
      determining protein FEM-2.
AB  - To investigate the causes and functional significance of rapid sex-determining
      protein evolution we compared three Caenorhabditis elegans genes encoding members
      of the protein phosphatase 2C (PP2C) family with their orthologs from another
      Caenorhabditis species (strain CB5161). One of the genes encodes FEM-2, a sex
      determining protein, while the others have no known sex-determining role. FEM-2's
      PP2C domain was found to be more diverged than the other PP2C domains, supporting
      the notion that sex-determining proteins are subjected to selective pressures
      that allow for or cause rapid divergence. Comparison of the positions of amino
      acid substitutions in FEM-2 with a solved three-dimensional structure suggests
      that the catalytic face of the protein is highly conserved among C. elegans,
      CB5161, and another closely related species C. briggsae. However, the non
      conserved regions of FEM-2 cannot be said to lack functional importance, since
      fem-2 transgenes from the other species were unable to rescue the germ-line
      defect caused by a C. elegans fem-2 mutation. To test whether fem-2 functions as
      a sex-determining gene in the other Caenorhabditis species we used RNA-mediated
      interference (RNAi). fem-2 (RNAi) in C. elegans and C. briggsae caused germ-line
      feminization, but had no noticeable effect in CB5161. Thus the function of fem-2
      in CB5161 remains uncertain.

PMID- 11821920
TI  - Actin and flagellin may have an N-terminal relationship.
AB  - There is an 8/13 sequence match between actin and flagellin in their N-terminal
      regions.

PMID- 11821921
TI  - Cloning of the L-lactate dehydrogenase gene from the ruminal bacterium
      Selenomonas ruminantium HD4.
AB  - A clone from a Selenomonas ruminantium HD4 Lambda ZAP II genomic library was
      isolated by its ability to complement the anaerobic growth deficiency of an
      Escherichia coli (pfl, ldh) double mutant. The 1.0-kb insert from the clone was
      sequenced and revealed a single open reading frame (ORF, 957-bp) which was
      preceded by a putative Shine-Dalgarno (SD) sequence (AGGGGG). The potential SD
      sequence corresponded to 3' 16S rRNA sequences of various Selenomonas strains.
      The ORF was predicted to encode a protein of 318 amino acids with a calculated
      molecular mass of 34,975 Da and an isoelectric point of 5.54. In addition, the
      ORF contained 51 mol % G + C and this is consistent with the average G + C
      content (54%) of the S. ruminantium chromosome. The cloned S. ruminantium gene
      exhibited 59% nucleotide identity and 61% deduced amino acid similarity with L
      lactate dehydrogenases (L-LDH) of Pediococcus acidilactici and Bacillus
      megaterium, respectively. Incorporation of the cloned S. ruminantium gene into E.
      coli DC1368 (pfl, ldh) restored anaerobic growth on glucose and L-LDH activity
      was detected in cell extracts. Because lactate accumulation within the rumen can
      be detrimental to animal performance, characterizing the gene(s) involved in
      lactate production by predominant ruminal bacteria will lead to a better
      understanding of lactate metabolism within the rumen.

PMID- 11821922
TI  - Cloning of the O-acetylserine lyase gene from the ruminal bacterium Selenomonas
      ruminantium HD4.
AB  - The gene coding for O-acetylserine lyase (OASL) was cloned from a Selenomonas
      ruminantium HD4 Lambda ZAP II genomic library by degenerative probe hybridization
      and complementation. Sequence analysis revealed a 933 bp ORF with a G + C content
      of 53%. The ORF had significant homology with enzymes involved in cysteine
      biosynthesis. A CuraBLASTN homology search showed that the ORF shared 59%
      nucleotide identity with the cysK of Bacillus subtilis. The deduced amino acid
      sequence exhibited high (>70%) similarity with the CysK of B. subtilis and other
      cysteine synthesis proteins from Mycobacterium tuberculosis, Mycobacterium
      leprae, and Spinacia oleracea. Further analysis predicted that the gene product
      was a member of the pyridoxal phosphate enzyme family and of cytoplasmic origin.
      Phylogenetic analysis clustered the S. ruminantium gene product with the OASLa
      isoform of B. subtilis and the OASLb isoforms of Streptococcus suis, Escherichia
      coli, and Campylobacter jejuni. The OASL of S. ruminantium HD4 was also able to
      complement the cysM cysK double mutations in Escherichia coli NK3 and allow for
      growth on minimal media that contained either sulfate or thiosulfate as the sole
      source of sulfur. These results suggest that the gene functions as a cysM in S.
      ruminantium HD4. In conclusion, this research describes the cloning and
      expression of an O-acetylserine lyase gene from the predominant ruminal anaerobe
      S. ruminantium HD4. To our knowledge, this is the first report characterizing
      genes involved in sulfur metabolism from the genus Selenomonas.

PMID- 11821923
TI  - Cloning, sequencing, and expression of a chitinase-encoding gene from Bacillus
      circulans No. 4.1.
AB  - A chitinase encoding gene from Bacillus circulans No. 4.1 was cloned in
      Escherichia coli by using pBluescript II SK. The recombinant plasmid containing
      the 2.6-kb chitinase gene was designated as pCHIB43. The nucleotide sequence
      revealed a single open reading frame containing 1794 bp and encoding 598 amino
      acids with a molecular mass of 65.78 kDa. The gene was sequentially deleted; the
      deletion clones were designated as pC66, pC6S, pSS6, and pEVS. The clones pC6S,
      pSS6, and pEVS hydrolyzed soluble chitin, but the ability to hydrolyze colloidal
      chitin was lost. The deduced amino acid sequence was investigated and found to be
      a chitin-binding domain and a catalytic domain containing 40 and 57 amino acid
      residues, respectively. A HindIII-SacI fragment of pSS6 was subcloned into
      pBluescript SK to reverse the orientation of the gene, and the resulting plasmid
      pSK43 did produce chitinase. Thus, the cloned gene was expressed under the
      control of a self-promoter.

PMID- 11821924
TI  - Immobilization results in sustained calcium transport in Nostoc calcicola Breb.
AB  - The uptake pattern of Ca2+ by the cyanobacterium Nostoc calcicola Breb in its
      freely suspended and immobilized form is comprised of two distinct phages; (a)
      rapid uptake for 1st 10 min followed by (b) slower transport at least up to 60
      min. Entrapment of cyanobacterial cells in polyvinyl foam always maintained a
      higher Ca2+ profile over freely suspended cells. Also, the intracellular Ca2+
      concentration was three times more in the former under similar experimental
      conditions. Whereas, illumination supported maximum Ca2+ transport in all the
      sets, darkness resulted in drastic reduction (90%) of Ca2+ uptake in freely
      suspended cells and least (15%) in polyvinyl entrapped cyanobacterial cells.
      Exogenously added ATP (10 microM) on the other hand, enhanced Ca2+ uptake in dark
      incubated freely suspended cells; ATP at the same concentration failed to bring
      out any significant enhancement in cation uptake in immobilized cells facing dark
      exposure. It was observed that these cells were still able to sustain sufficient
      ATP preserves to drive active transport of Ca2+ even in the dark. Furthermore,
      the immobilized cells exhibited remarkable Ca2+ transport rate even at the age of
      20 and 50 days at which its free living counterpart took up insignificant Ca2+.
      These findings suggest the improved metabolic efficiency of polyvinyl foam
      entrapped cells over freely suspended cells in terms of Ca2+ accumulation and its
      possible use as a bioreactor for metal accumulation/removal in repetitive cycles
      without any measurable loss in cell biomass.

PMID- 11821925
TI  - Relationship between the persistence of mer operon sequences in Escherichia coli
      and their resistance to mercury.
AB  - Studies related to geographic distribution of E. coli carrying mer operon
      sequences were carried out on the Indian subcontinent. Out of the 80 E. coli
      isolates, collected from five geographically distinct regions of India, 68 were
      found to be resistant to one or the other heavy metal used in the study. Among
      these isolates, 36 were found to be resistant to the inorganic form (HgCl2) and
      only 5 to resist both the inorganic and organic forms of mercury. Colony
      hybridization studies revealed 35 isolates out of 68 to hybridize with the probe.
      Interestingly, some of the mercury-sensitive isolates (Hgs), especially from the
      Dal Lake, were found positive in hybridization studies. These findings, supported
      by mercury volatilization studies, indicate the presence of
      nonfunctional/vestigial mer sequences in the isolates collected from different
      environments. On the other hand, few of the mercury-resistant isolates (Hgr) from
      the Yamuna River did not show any sign of hybridization. Further, volatilization
      studies also indicated an alternate mode of resistance mechanism operating in
      them. The studies demonstrate that the mer operon sequences share very high
      homology among the E. coli isolates collected from different geographical
      locations, and this metal resistance may be a genetic character that arose from a
      common ancestral background.

PMID- 11821926
TI  - Identification of genes essential for growth at high salt concentrations using
      salt-sensitive mutants of the cyanobacterium Synechocystis sp. strain PCC 6803.
AB  - A collection of 17 salt-sensitive mutants of the cyanobacterium Synechocystis sp.
      strain PCC 6803 was obtained by random cartridge mutagenesis. The genes coding
      for proteins essential for growth at high salt concentrations were mapped on the
      completely known genome sequence of this strain. The two genes coding for enzymes
      involved in biosynthesis of the osmolyte glucosylglycerol were affected in nine
      mutants. Two mutants defective in a glycoprotease encoding gene gcp showed a
      reduced salt resistance. Four genes were identified not previously known to be
      essential for salt tolerance in cyanobacteria. These genes (slr1799, slr1087,
      sll1061, and sll1062) code for proteins not yet functionally characterized.

PMID- 11821927
TI  - Physiological characterization and genetic engineering of Pseudomonas corrugata
      for medium-chain-length polyhydroxyalkanoates synthesis from triacylglycerols.
AB  - Pseudomonas belonging to the rRNA-DNA homology group I produce medium-chain
      length (mcl)-polyhydroxyalkanoates (PHA). We show that P. corrugata, a member of
      this group, accumulates 0.5-1.0 g of mcl-PHA/L of culture when grown on glucose
      (Gl) or oleic acid (Ol). The predominant monomers of Gl-PHA and Ol-PHA are beta
      hydroxydecanoate and beta-hydroxyoctanoate, respectively. The molecular masses
      and polydispersity of P. corrugata PHAs are higher than those typically found
      with other Pseudomonas. We electrotransformed P. corrugata with a plasmid
      pCN51lip-1 carrying Pseudomonas lipase genes to generate strain III111-1. The
      recombinant strain grew on intact triacylglycerols (TAGs) to 1.9-2.7 g of cell
      dry-weight/L of culture. The yields and the predominant repeat-units of PHAs
      obtained from the lard- and tallow-grown III111-1 were similar to those of Ol-PHA
      from wild-type cells. In contrast to other Pseudomonas species, P. corrugata
      III111-1 grown on TAGs at temperatures up to 36 degrees C was not significantly
      affected with regard to cell yields, amounts of PHA produced, and the repeat unit
      compositions of the polymer.

PMID- 11821928
TI  - Reduction of sulfide, ammonia compounds, and adhesion properties of Lactobacillus
      casei strain KE99 in vitro.
AB  - The ability of Lactobacillus casei strain KE99 to reduce sulfide, ammonia, and to
      adhere to bio-surfaces was characterized and compared with three lactobacillus
      reference strains. Sulfide reduction by strain KE99 in MRS broth increased
      exponentially after 10-h growth and reached a maximum (>300 ppm reduction) within
      48 h. KE99 demonstrated a maximum reduction of sulfide under anaerobic (341 ppm)
      growth conditions at pH 6.0-8.0 range. Maximum anaerobic reduction of sulfide was
      demonstrated by L. casei 393 at pH 7.0 (272 ppm); L. rhamnosus at pH 8.0 (277
      ppm); and L. reuteri at pH 7.0 (244 ppm). KE99 reduced sulfide more (p < 0.0001)
      in MRS broth spiked with Na2S (374 ppm) than (NH4)2S (340 ppm) salts. Ammonia
      reduction by strain KE99 and the three lactobacillus reference strains in MRS
      broth was low. Ammonia reduction reached a maximum within 36 h and remained
      unchanged over extended incubations of 48 h to 72 h or further. KE99 reduced
      ammonium sulfate (37 ppm) more readily than the nitrate (31 ppm), hypophosphate
      (29 ppm), or chloride (20 ppm) salts of ammonia. KE99 and the three reference
      strains of lactobacilli demonstrated avid binding to Bio-coat (Cn type-I, Cn type
      IV, laminin, fibronectin), Matrigel, and Caco-2 cell monolayers in vitro. The
      number of lactobacilli binding to Caco-2 was estimated at 74/cell with strain
      KE99, which was significantly higher compared with 40/cell (p < 0.0001), 26/cell
      (0.0001), and 64/cell (p < 0.002) with L. casei 393, L. reuteri, and L.
      rhamnosus, respectively. The interaction of KE99 to immobilized Cn type-I was
      saturable and reached an equilibrium within 1 h at room temperature. KE99 binding
      to Cn type-I occurred at a wide pH range and was biphasic with maximum binding at
      pH 5.5 and 7.5. Inhibition and binding-displacement experiments with different
      salts and sugars suggested that the KE99 binding to immobilized Cn type-I may
      involve a combination of electrostatic and lectin-type interactions. KE99
      effectively detached the Cn-adherent E. coli O157:H7 in the range of 55%
      (ATCC43895) to 76% (ATCC43894). The binding-displacement values for L. casei 393,
      L. reuteri and L. rhamnosus to detach Cn-adherent E. coli O157:H7 (ATCC43894)
      were 66 +/- 4%, 59 +/- 2%, and 64 +/- 2%, respectively. Also, a reconstituted
      solution of the freeze-dried KE99 preparation effectively detached the Cn
      adherent E. coli O157:H7 in a dose-dependent manner that reached a binding
      displacement equilibrium of 85% at a 1% wt/vol KE99 concentration.

PMID- 11821929
TI  - The endopolysaccharide metabolism of the hyperthermophilic archeon Thermococcus
      hydrothermalis: polymer structure and biosynthesis.
AB  - The endopolysaccharide accumulated by Thermococcus hydrothermalis was extracted
      and purified from a 4 h culture. It presented an "amylopectin-like" structure
      with an average chain length of 14 and a ramification degree of 7.5%. The
      glucosyltransferase was isolated, partially purified and characterized. The
      molecular mass was 42 kDa by SDS PAGE and 85 +/- 5 kDa by gel filtration. This
      enzyme was able to use both Uridine-5'-DiPhosphoGlucose (UDPG) and Adenosine-5'
      DiPhosphoGlucose (ADPG) as substrates. Optimal pH and temperature for the enzyme
      were 5.5 and 80 degrees C, respectively. In the presence of 3.2 mM ADPG, the half
      life of the protein was 6 min at 110 degrees C. The apparent Km value with the
      two substrates was 0.9 mM, but the Vmax was 9.7 fold higher for ADPG. A branching
      activity was also detected at high temperature, up to 80 degrees C by different
      methods: phosphorylase stimulation, iodine, and branching linkage assays.

PMID- 11821930
TI  - Adhesive property of Bifidobacterium lactis LKM512 and predominant bacteria of
      intestinal microflora to human intestinal mucin.
AB  - The adhesive property to the intestinal mucin of Bifidobacterium lactis LKM512,
      B. longum, B. breve, B. bifidum, B. adolescentis, B. infantis, Bacteroides
      vulgatus, Bacteroides distasonis, Eubacterium aerofaciens, Clostridium
      perfringens, Escherichia coli, and Lactobacillus acidophilus were examined.
      Adhesive rate of LKM512 to the mucin was significantly (p < 0.05, 0.01, or 0.001)
      stronger than the other strains from 2 to 100 time. Though the adhesive property
      of many strains was almost same to the mucin of 20-year-old and 50-year-old
      generations, in case of 4-month-old was different. Adhesive inhibitory effect of
      C. perfringens to the mucin by LKM512 was examined. Under the condition that
      LKM512 was 108/ml and that C. perfringens was 106/ml, adhesion of C. perfringens
      to the mucin was inhibited at 99.6%, when LKM512 adhered in advance. There was
      the strong inhibition of adhesion at 74.0%, when C. perfringens adhered to mucin
      in advance. Thus, LKM512 can inhibit the adhesion of harmful bacteria to the
      intestinal mucin, the possibility of using as a probiotic strain has to be
      verified.

PMID- 11821931
TI  - Molecular cloning and phylogenetic analysis of new human endogenous retrovirus
      HERV-W family in cancer cells.
AB  - A human endogenous retroviral family (HERV-W) has recently been described that is
      related to multiple sclerosis-associated retrovirus (MSRV) sequences. By using
      the PCR approach with human genomic DNA derived from cancer cell lines (HepG2,
      Jurkat, MCF7, UO-31), five env fragments of HERV-W family were newly identified
      and analyzed. They showed a high degree of nucleotide sequence similarity (94
      99%) with that of the HERV-W. Translation of the env fragments showed no
      frameshift and termination codon by deletion/insertion or point mutation in
      clones HepG2-1 and JUR-3. The ratio of synonymous to non-synonymous substitutions
      indicated that negative selective pressure is acting on HepG2-1 and JUR-3
      sequences. These env gene sequences could be associated with an active provirus
      in human cancer cells (HepG2 and Jurkat). The HepG2-1 and JUR-3 showed sister
      relationship with the HERV-W and W-7-1 derived from human Chromosome (Chr) 7.
      Phylogenetic analysis from the HERV-W family indicated close relationships of the
      env gene sequences across human chromosomes.

PMID- 11821932
TI  - Inoculation of chicks with viable non-colonizing strains of Campylobacter jejuni:
      evaluation of protection against a colonizing strain.
AB  - We have treated chicks with viable non-colonizing mutant strains of Campylobacter
      jejuni to test these as a possible vaccine. We found that intramuscular
      inoculation with and without adjuvant, and with or without a concomitant oral
      dose of non-colonizing strains, failed to provoke protective immunity.

PMID- 11821933
TI  - MutS2 family protein from Pyrococcus furiosus.
AB  - MutS2 protein of Pyrococcus furiosus has been cloned and over-expressed. Initial
      characterization reveals that PfuMutS2 possesses a thermostable ATPase activity
      and a thermostable, nonspecific DNA binding activity. However, PfuMutS2 does not
      have any detectable mismatch-specific DNA binding activity. It is the first in
      vitro characterization of an MutS2 family protein.

PMID- 11821934
TI  - Regulated and prolonged expression of mIFN(alpha) in immunocompetent mice
      mediated by a helper-dependent adenovirus vector.
AB  - A major goal in gene therapy is to develop efficient gene transfer protocols that
      allow tissue-specific, long-term and tightly regulated expression of the desired
      transgene. This objective is becoming more attainable through the co-evolution of
      gene transfer vectors and regulation systems. The ideal vector should efficiently
      transduce non-dividing cells with minimal toxicity, thus endowing the system with
      persistent transgene expression. The helper-dependent adenovirus vectors meet
      these requirements, as demonstrated in various studies in the literature. The
      most promising regulation system is the tet-on system, which has low basal
      transcriptional activity and high inducibility. To explore the regulated
      transgene expression in the context of a helper-dependent vector, we constructed
      the HD-TET-IFN vector, containing the mIFN(alpha) gene under the control of the
      tetracycline inducible transactivator rtTA2(s)-S2. Mice injected with HD-TET-IFN
      showed high levels of serum mIFN(alpha) only upon transcriptional activation. The
      transgene expression was reinducible to the same high level up to 3 months p.i.,
      and the amount of expressed cytokine could be regulated by dosing doxycycline.
      Transcriptional activation of mIFN(alpha) induced by doxycycline resulted in
      prolonged survival and reduced liver damage in HD-TET-IFN-injected mice
      challenged with a lethal dose of coronavirus. Activation of antiviral genes
      mediated by doxycycline-dependent mIFN(alpha) expression was also observed at low
      HD-TET-IFN doses. The possibility of controlling gene expression by the
      combination of HD vectors and the latest tet-on transactivator also holds promise
      for studying gene function in other animal models.

PMID- 11821935
TI  - Lectin binding and endocytosis at the apical surface of human airway epithelia.
AB  - The specificity of lectin binding to distinct saccharides makes them valuable
      reagents for investigation and identification of cells within complex tissues and
      potentially for delivery of agents into cells. Therefore we examined lectin
      binding to airway epithelia. We used an in vitro model of primary cultures of
      well-differentiated human airway epithelia and applied the lectins to the apical
      surface of living epithelia. This approach limited binding specifically to the
      extracellular surface of the apical membrane. Of 32 lectins studied, we found 15
      that bound to the apical membrane. The pattern varied from diffuse binding to the
      surface of nearly all the cells, to binding to a small subset of the cells. Our
      data combined with earlier studies identify lectins that may be used to detect
      specific populations of epithelial cells. Because lectins may be used to deliver
      a variety of agents, including gene transfer vectors, to airway cells, we
      examined endocytosis of lectins. We found that several lectins bound to the
      apical surface were actively taken up into the cells. These data may be of value
      for studies of airway epithelial structure and may facilitate the targeting of
      the epithelial apical surface.

PMID- 11821936
TI  - In vivo myocardial gene transfer: optimization and evaluation of intracoronary
      gene delivery in vivo.
AB  - Clinical reports suggest that intracoronary delivery of adenoviruses encoding
      angiogenic growth factors, or their transactivators, has a therapeutic benefit.
      However there has not been a systematic assessment of the transfection efficiency
      of this technique in vivo. In rabbits we investigated the efficiency of
      myocardial gene transfer following intracoronary infusion of 1 x 10(-10) -1 x
      10(12) p.f.u. of adenovirus in combination with interventions to enhance
      transfection. In five standard short axis sections, we were barely able to detect
      reporter gene expression following unmodified intracoronary infusion. Efficiency
      was not enhanced by the exclusion of blood and the increase of intracoronary
      dwell time through occlusive engagement of the left coronary ostium enabled by
      oxygenated perfluorocarbon emulsion as viral diluent. Of the interventions and
      pretreatments designed to increase vascular permeability, VEGF, calcium-free
      viral diluent and adenosine, only the latter tended to increase efficiency.
      However an intervention designed to increase the myocardial transcapillary
      gradient, by increasing venular pressure with pulmonary artery occlusion and
      arteriolar pressure with occlusion of the aorta above the coronary ostia,
      increased transfection efficiency by two orders of magnitude. Unfortunately the
      clinical utility of this technique may be limited by accompanying cardiac
      dilation and marked elevations in intracardiac pressure.

PMID- 11821937
TI  - Prevention of restenosis by a herpes simplex virus mutant capable of controlled
      long-term expression in vascular tissue in vivo.
AB  - Neointimal hyperplasia resulting from vascular smooth muscle cell (SMC)
      proliferation and luminal migration is the major cause of autologous vein graft
      failure following vascular coronary or peripheral bypass surgery. Strategies to
      attenuate SMC proliferation by the delivery of oligonucleotides or genes
      controlling cell division rely on the use of high concentrations of vectors, and
      require pre-emptive disruption of the endothelial cell layer. We report a
      genetically engineered herpes simplex virus (HSV-1) mutant that, in an in vivo
      rabbit model system, infects all vascular layers without prior injury to the
      endothelium; expresses a reporter gene driven by a viral promoter with high
      efficiency for at least 4 weeks; exhibits no systemic toxicity; can be eliminated
      at will by administration of the antiviral drug acyclovir; and significantly
      reduces SMC proliferation and restenosis in vein grafts in immunocompetent hosts.

PMID- 11821938
TI  - Tissue-specific expression of an anti-proliferative hybrid transgene from the
      human smooth muscle alpha-actin promoter suppresses smooth muscle cell
      proliferation and neointima formation.
AB  - The retinoblastoma protein (Rb), a key regulator of cell cycle progression, can
      bind the transcription factor E2F converting it from a positive transcriptional
      factor capable of driving cells into S phase into a negative complex which
      arrests cells in G1. We have created a potent transcriptional repressor of E2F
      dependent transcription by fusing the C-terminal fragment of Rb (p56) to the DNA
      and DP1-binding domains of E2F. Because the expression of E2F/56 fusion protein
      from a constitutive promoter was incompatible with virus growth, adenovirus
      constructs were prepared where transgenes were expressed from a fragment of the
      smooth muscle alpha-actin (SMA) promoter. Immunoblot and beta-galactosidase
      staining demonstrated smooth muscle-specific expression of this transcriptional
      element in vitro. The SMA-p56 and SMA-E2F/p56 adenoviral constructs also induced
      G0/G1 cell cycle arrest specifically in smooth muscle cells. Following
      administration to rat tissues, the SMA-beta-galactosidase construct exhibited
      expression in balloon-injured carotid arteries, but not in liver, bladder or
      skeletal muscle. Local delivery of the SMA-E2F/p56 adenoviral construct to
      balloon-injured carotid arteries inhibited intimal hyperplasia. Our results
      demonstrate that local delivery of the SMA-E2F/p56 adenoviral construct can limit
      intimal hyperplasia in balloon-injured vessels, while avoiding toxicity that
      could occur from the dissemination and expression of the viral transgene.

PMID- 11821939
TI  - Collagen II-pulsed antigen-presenting cells genetically modified to secrete IL-4
      down-regulate collagen-induced arthritis.
AB  - We explored the possibility that pulsed antigen-presenting cells (APC) provide a
      model vector system for site-specific delivery of immunosuppressive proteins
      during collagen-induced arthritis (CIA), an animal model for rheumatoid
      arthritis. Thus, mice were treated with either B cells or macrophages engineered
      to secrete IL-4 and loaded (or not) with type II collagen (CII). Systemic
      injection of an IL-4-producing B cell hybridoma resulted in a reduction of
      arthritis severity which was further improved when APC were incubated with CII
      before their transfer. Unmanipulated B cells loaded with CII also exerted a
      potent suppressive effect. Likely, clinical amelioration was observed in mice
      given at priming syngeneic bone marrow-derived macrophages producing IL-4 and
      pulsed with CII in comparison to the other groups. When the same dose of cells
      was transferred at disease onset, a moderate beneficial effect was observed.
      Whatever the APC inoculated, the beneficial effect did not rely upon an IL-4
      driven shift towards Th2 phenotype. Systemic administration of fluorescent dye
      labeled macrophages to arthritic mice has shown that some of these cells rapidly
      migrate to joints. Moreover, IL-4 transfected macrophages retained their potent
      capacity to present CII peptides to T cells. These findings validate the use of
      CII peptide-loaded engineered APC as therapeutic vector cells in CIA and allow
      consideration of this strategy for the administration of various anti
      inflammatory proteins.

PMID- 11821940
TI  - Long-term RNase P-mediated inhibition of HIV-1 replication and pathogenesis.
AB  - Advances in genetic analysis and a greater understanding of human
      immunodeficiency virus (HIV) molecular pathogenesis have identified critical
      viral targets for gene interference strategies. RNase P molecules have been
      proposed as a novel approach for gene targeting based upon their potent catalytic
      activity, as well as versatile external guide sequence (EGS) which can be
      modified to specifically recognize almost any target mRNA. We designed a
      truncated EGS to specifically recognize the highly conserved U5 region of HIV-1
      mRNA and mediate subsequent cleavage of hybridized mRNA by the RNase P enzyme
      component. The active U5-EGS (560), as well as a disabled U5 EGS (560D) control,
      were cloned into plasmids containing proviral constructs and transfected into a
      CD4(+) T cell line that was thereafter infected with HIV-1 MN. CD4(+) T cells
      treated with the active U5 EGS (560) were observed to maintain CD4(+) expression
      and did not produce HIV p24 gag antigen, form syncytia or undergo apoptosis up to
      30 days after infection. Identical cells expressing the inactivated form of the
      U5 RNase P EGS completely down-regulated CD4 expression, produced elevated levels
      of HIV-1, formed large syncytia and underwent apoptosis similar to untreated
      cells. HIV-1 replication and related cytopathology can be effectively inhibited
      in CD4(+) T cells expressing a protective U5 EGS (560).

PMID- 11821941
TI  - Designing gene therapy vectors: avoiding immune responses by using tissue
      specific promoters.
AB  - Attempts to correct genetic disorders by gene therapy have been hindered by
      various problems including unwanted immune responses against the gene product. It
      has been shown that immune responses with DNA vaccines after i.m. injection of
      antigen-encoding plasmid DNA are primed solely by professional antigen-presenting
      cells (APC), even though myocytes are the primary type of cell transfected. This
      possibly involves direct transfection of some APC in regional lymph nodes
      draining the injected muscle. Here we have used plasmid DNA vaccines that express
      hepatitis B surface antigen (HBsAg) to evaluate the possibility of abrogating
      these immune responses by use of a tissue-specific promoter that does not drive
      expression in APC. We show that HBsAg-specific humoral or cell-mediated responses
      are not induced in mice when the muscle-specific human muscle creatine kinase
      promoter is used in place of the ubiquitous cytomegaloviral promoter to drive
      expression of HBsAg. This may have significance in the field of gene therapy
      where one aims to achieve stable expression of the desired gene product without
      interference from the host immune response.

PMID- 11821945
TI  - Akt is required for Axl-Gas6 signaling to protect cells from E1A-mediated
      apoptosis.
AB  - Adenovirus type 5 E1A protein (E1A) associates with anti-tumor activities by
      reversing the transformed phenotype, inhibiting metastasis, and inducing
      apoptosis. We have previously identified that E1A suppresses the expression of
      Axl, a transforming tyrosine kinase and that Axl-Gas6 receptor-ligand interaction
      prevents E1A transfectants from apoptosis induced by serum deprivation. To
      determine how the Axl-Gas6 interaction prevents E1A-mediated apoptosis, we
      analysed the expression of anti-apoptotic molecules and found that the activated
      form of Akt was suppressed in the E1A transfectant ip 1-E1A and that Gas6 was
      able to activate Akt in ip 1-E1A cells reexpressing Axl (ip 1-E1A-Axl). To
      determine whether activated Akt is required to prevent E1A-mediated apoptosis, ip
      1-E1A-Axl cells were treated with the phosphatidylinositol-3'-OH kinase inhibitor
      wortmannin or transfected with a dominant negative Akt mutant. In both cases,
      Gas6 no longer protected the cells from serum deprivation-induced apoptosis.
      Thus, we conclude that activated Akt is required for Axl-Gas6 signaling to
      prevent E1A-mediated apoptosis induced by serum deprivation. Downstream molecules
      of Akt, including NF-kappaB, Fas ligand, and BAD were examined, among which
      phosphorylation of BAD by Axl-Gas6 signaling is associated with the anti
      apoptotic activity of Akt in our study.

PMID- 11821946
TI  - Low glucose-enhanced TRAIL cytotoxicity is mediated through the ceramide-Akt-FLIP
      pathway.
AB  - To examine whether the tumor microenvironment alters cytokine-induced
      cytotoxicity, human prostate adenocarcinoma DU-145 cells were exposed to tumor
      necrosis factor-related apoptosis-inducing ligand (TRAIL) and/or glucose
      deprivation, a common characteristic of the tumor microenvironment. TRAIL alone
      reduced cell survival in a dose-dependent manner. Glucose deprivation alone
      induced no cytotoxicity within 4 h. However, the combination of TRAIL (50 ng/ml)
      and glucose deprivation for 4 h increased cell death and PARP cleavage by
      promoting activation of caspase-8 and caspase-3, relative to that of TRAIL alone.
      Similar results were observed in human colorectal carcinoma CX-1 cells. Data from
      immunoblotting analysis reveal that glucose deprivation-enhanced TRAIL
      cytotoxicity is inversely related to the intracellular level of FLICE inhibitory
      protein (FLIP) but not that of death receptor 5 (DR5). Results from mass
      spectrometry show that glucose deprivation elevates ceramide. The elevation of
      ceramide may cause dephosphorylation of Akt and maintain dephosphorylation of Akt
      in the presence of TRAIL and then subsequently down-regulate the expression of
      FLIP. Taken together, the present studies suggest that glucose deprivation
      enhances TRAIL-induced cytotoxicity through the ceramide-Akt-FLIP pathway.

PMID- 11821947
TI  - ERK signalling and oncogene transformation are not impaired in cells lacking A
      Raf.
AB  - Previous studies have indicated an important role for the Raf family of protein
      kinases in controlling cellular responses to extracellular stimuli and activated
      oncogenes, through their ability to activate the MEK/ERKs. To investigate the
      specific role of A-Raf in this process we generated A-Raf deficient mouse
      embryonic fibroblasts (MEFs) and embryonic stem (ES) cells by gene targeting and
      characterized their ability to undergo proliferation, differentiation, apoptosis,
      ERK activation, and transformation by oncogenic Ras and Src. The A-Raf deficient
      cells are not disrupted for any of these processes, despite the fact that this
      protein is normally expressed at high levels in both cell types. This implies
      either that A-Raf plays no role in MEK/ERK activation, that its function is fully
      compensated by other Raf proteins or MEK kinases or that its role in MEK/ERK
      activation is highly tissue-specific. Interestingly, B-Raf and Raf-1 activity
      towards MEK as measured by the immunoprecipitation kinase cascade assay are both
      significantly increased in the A-Raf deficient MEFs.

PMID- 11821948
TI  - The interaction of p53 with the nuclear matrix is mediated by F-actin and
      modulated by DNA damage.
AB  - The tumour suppressor protein p53 is localized in the cell nucleus where it
      serves to initiate cellular responses to a variety of stresses, particularly DNA
      damage and has the capacity to transactivate stress response genes. An emerging
      body of evidence indicates that its action is also exerted through direct protein
      protein interactions. An approach to understanding p53 function has been to
      analyse its positioning in relation to nuclear structures and we have shown that
      p53 can associate with the nuclear matrix. A potential nuclear matrix component
      for this association is actin. Here we show that p53 interacts with nuclear F
      actin and we map the domains involved in this interaction. Using fluorescence
      resonance energy transfer, we demonstrate that the partition of p53 between F
      actin bound and unbound forms is not constant, but is modulated by the presence
      of DNA damage, which increases binding. Our results indicate that the dynamic
      interaction of p53 with the nuclear matrix has to be considered for a full
      understanding of the mechanisms of the p53-mediated cellular response to DNA
      damage.

PMID- 11821949
TI  - The gene for interleukin-21 receptor is the partner of BCL6 in t(3;16)(q27;p11),
      which is recurrently observed in diffuse large B-cell lymphoma.
AB  - BCL6 translocation affecting the chromosomal band 3q27 can involve a number of
      non-immunoglobulin (non-IG) gene loci as partners. We report here that the gene
      for interleukin-21 receptor (IL-21R) is the partner of BCL6 in t(3;16)(q27;p11)
      translocation. The two breakpoints on 16p11 of a lymphoma cell line YM and case
      no. 1012 with diffuse large B-cell lymphoma, both of which carried t(3;16), were
      localized within the 27-kb intron 1 of IL-21R. As a result of t(3;16), the
      promoter region of IL-21R was substituted for the regulatory sequences of BCL6 in
      the same transcriptional orientation. Reverse transcriptase-mediated polymerase
      chain reaction revealed chimeric mRNA consisting of two non-coding exons 1a/1b of
      IL-21R and coding exons of BCL6 in both lymphoma cells. Fluorescence in situ
      chromosomal hybridization of YM metaphase cells revealed fusion signals that
      contained both the BCL6 and IL-21R sequences on the der(3)t(3;16) chromosome. IL
      21R was actively transcribed in YM cells, while BCL6 that was under the control
      of the IL-21R promoter was only moderately expressed at the mRNA and protein
      level. We constructed expression plasmid of BCL6 that followed the promoter
      sequences of IL-21R. COS-7 cells transiently transfected with the plasmid
      expressed high level Bcl-6 protein and displayed nuclear staining with a
      characteristic punctate pattern by immunofluorescence, indicating that expression
      of BCL6 can be enhanced by t(3;16). This study added to the list of non-IG
      partners of BCL6 translocations a new class of gene, i.e. cytokine receptor gene,
      the expression of which is closely associated with lymphoid cells.

PMID- 11821950
TI  - The hepatitis B virus X protein abrogates Bcl-2-mediated protection against Fas
      apoptosis in the liver.
AB  - The role of the hepatitis B virus protein HBx in liver cell proliferation and
      apoptosis remains controversial. Using a transgenic mouse model, we have recently
      shown that HBx stimulates the apoptotic turnover of hepatocytes, independently of
      p53. In this paper, we tested whether the proapoptotic function of HBx can
      interfere with Bcl-2 during hepatic apoptosis in vivo. HBx transgenic mice were
      crossed with PK-hBcl-2 mice that are protected against Fas killing by
      constitutive overexpression of Bcl-2 in hepatocytes. In a lethal challenge with
      Fas antibodies, HBx expressed at low levels restored sensitivity to Fas-mediated
      apoptosis and fulminant hepatic failure in mice overexpressing Bcl-2.
      Furthermore, cytochrome c release from mitochondria and caspase 3 activation were
      restored to normal levels in HBx/Bcl-2 mice during transduction of the Fas
      signal. Thus, the proapoptotic activity of HBx overcomes or bypasses the
      inhibitory effect of Bcl-2 against Fas cytotoxicity. This effect was not
      apparently mediated through downregulation of the PK-hBcl-2 transgene or via
      delocalization of the Bcl-2 protein, and a direct interaction of HBx with Bcl-2,
      Bcl-X(L) or Bax could not be evidenced in yeast two-hybrid assays. We further
      show that apoptosis induced by ectopic expression of HBx is associated with
      mitochondrial membrane alterations and caspase 3 activation. Our data indicate
      that the dominant function of HBx upon Bcl-2-regulated control of apoptosis might
      play an important role in the pathogenesis of chronic hepatitis B.

PMID- 11821951
TI  - Physical and transcript map of the region between D6S264 and D6S149 on chromosome
      6q27, the minimal region of allele loss in sporadic epithelial ovarian cancer.
AB  - We have previously shown a high frequency of allele loss at D6S193 (62%) on
      chromosomal arm 6q27 in ovarian tumours and mapped the minimal region of allele
      loss between D6S297 and D6S264 (3 cM). We isolated and mapped a single non
      chimaeric YAC (17IA12, 260-280 kb) containing D6S193 and D6S297. A further
      extended bacterial contig (between D6S264 and D6S149) has been established using
      PACs and BACs and a transcript map has been established. We have mapped six new
      markers to the YAC; three of them are ESTs (WI-15078, WI-8751, and TCP10). We
      have isolated three cDNA clones of EST WI-15078 and one clone contains a complete
      open reading frame. The sequence shows homology to a new member of the
      ribonuclease family. The other two clones are splice variants of this new gene.
      The gene is expressed ubiquitously in normal tissues. It is expressed in 4/8
      ovarian cancer cell lines by Northern analysis. The gene encodes for a 40 kDa
      protein. Direct sequencing of the gene in all the eight ovarian cancer cell lines
      did not identify any mutations. Clonogenic assays were performed by transfecting
      the full-length gene in to ovarian cancer cell lines and no suppression of growth
      was observed.

PMID- 11821952
TI  - bFGF signaling and v-Myb cooperate in sustained growth of primitive erythroid
      progenitors.
AB  - The development of red blood cells from hematopoietic progenitors requires the
      interplay of specific extracellular factors and transcriptional regulators. Here
      we have identified an erythroid progenitor that is critically dependent on bFGF
      and requires expression of AMV v-Myb for sustained proliferation in vitro,
      indicating that bFGF and Myb proteins cooperate in these cells. In the presence
      of bFGF such v-Myb cells are completely blocked in their ability to differentiate
      and exhibit an exceptionally high proliferative potential and long lifespan in
      vitro. Interestingly, in the absence of bFGF cells effectively differentiate into
      mature erythrocytes, irrespective of constitutive and elevated levels of v-Myb.
      We also demonstrate that these cells express high levels of FGF receptor type 1
      (FGFR1) and that phospholipase C(gamma) (PLC(gamma)) is one of the important
      molecules in FGF receptor signaling. Our studies suggest that bFGF, in
      cooperation with Myb proteins, represents an important factor for determining
      erythroid lineage choice. These findings unravel a so far unidentified link
      between extracellular signaling and Myb in hematopoietic cells.

PMID- 11821953
TI  - Induction of retinoic acid receptor-beta suppresses cyclooxygenase-2 expression
      in esophageal cancer cells.
AB  - Since retinoic acid receptor (RAR)-beta mRNA is frequently lost during esophageal
      carcinogenesis and esophageal cancer cells that do not express RAR-beta are
      resistant to retinoic acid (RA), we stably transfected RAR-beta expression vector
      into an esophageal cancer cell line TE-8 and an antisense RAR-beta into TE-3
      cells. Transfection of RAR-beta decreased cell growth and colony formation and
      induced apoptosis in TE-8 cells. Antisense RAR-beta-transfected TE-3 cells had a
      shorter doubling time and became resistant to RA. Induction of RAR-beta decreased
      COX-2 expression in RAR-beta transfected TE-8 cells, whereas antisense RAR-beta
      transfected TE-3 cells increased COX-2 expression. The inhibitory effect of RAR
      beta on COX-2 expression was further enhanced in the presence of RA, which was
      blocked by an RAR antagonist. The synthetic retinoid N-(4
      hydroxyphenyl)retinamide, which does not bind effectively to RAR-beta, had no
      effect on COX-2 suppression. Furthermore, RA blocked bile acid-induced COX-2
      expression and prostaglandin E(2) production only in the RAR-beta positive cells.
      Our data demonstrated that anticancer effect of RAR-beta may be related to its
      ability to suppress COX-2 expression and support that the loss of RAR-beta
      expression may contribute to esophageal carcinogenesis.

PMID- 11821954
TI  - Characterization of viral-cellular fusion transcripts in a large series of HPV16
      and 18 positive anogenital lesions.
AB  - Persistent high risk type human papillomavirus (HR-HPVs) infections induce
      dysplasia or cancer of the anogenital tract, most notably of the uterine cervix.
      The viral genome usually persists and replicates as an episomal molecule in early
      dysplasia, whereas in advanced dysplasia or cervical cancer HPV genomes are
      frequently integrated into the chromosomal DNA of the host cell. Previous studies
      suggested that modification of critical cellular sequences by integration of HPV
      genomes might significantly contribute to the neoplastic transformation of
      anogenital epithelia (insertional mutagenesis). This prompted us to characterize
      the integration loci of high risk HPV genomes in a large set of genital lesions.
      We amplified E6/E7 oncogene transcripts derived from integrated HPV16 and HPV18
      genomes and characterized in detail the co-transcribed cellular sequences of 64
      primary genital lesions and five cervical cancer cell lines. Database analyses of
      the cellular parts of these fusion transcripts revealed 51 different integration
      loci, including 26 transcribed genes (14 known genes, 12 EST sequences with
      unknown gene function). Seventeen sequences showed similarity to repetitive
      elements, and 26 sequences did not show any database match other than genomic
      sequence. Chromosomal integration loci were distributed over almost all human
      chromosomes. Although we found HPV sequences integrated into cancer related genes
      and close to fragile sites, no preferential site or integration motif could be
      identified. These data demonstrate that target directed insertional mutagenesis
      might occur in few HPV-induced anogenital lesions, however, it is rather the
      exception than the rule.

PMID- 11821955
TI  - Histone deacetylases inhibitors as anti-angiogenic agents altering vascular
      endothelial growth factor signaling.
AB  - Angiogenesis is a complex biological process involving the coordinated modulation
      of many genes. Histone deacetylases (HDAC) are a growing family of enzymes that
      mediate the availability of chromatin to the transcriptional machinery.
      Trichostatin-A (TSA) and suberoylanilide hydroxamic acid (SAHA), two HDAC
      inhibitors known to relieve gene silencing, were evaluated as potential
      antiangiogenic agents. TSA and SAHA were shown to prevent vascular endothelial
      growth factor (VEGF)-stimulated human umbilical cord endothelial cells (HUVEC)
      from invading a type I collagen gel and forming capillary-like structures. SAHA
      and TSA inhibited the VEGF-induced formation of a CD31-positive capillary-like
      network in embryoid bodies and inhibited the VEGF-induced angiogenesis in the CAM
      assay. TSA also prevented, in a dose-response relationship, the sprouting of
      capillaries from rat aortic rings. TSA inhibited in a dose-dependent and
      reversible fashion the VEGF-induced expression of VEGF receptors, VEGFR1, VEGFR2,
      and neuropilin-1. TSA and SAHA upregulated the expression by HUVEC of semaphorin
      III, a recently described VEGF competitor, at both mRNA and protein levels. This
      effect was specific to endothelial cells and was not observed in human
      fibroblasts neither in vascular smooth muscle cells. These observations provide a
      conspicuous demonstration that HDAC inhibitors are potent anti-angiogenic factors
      altering VEGF signaling.

PMID- 11821956
TI  - E2Fs up-regulate expression of genes involved in DNA replication, DNA repair and
      mitosis.
AB  - The E2F family of transcription factors plays a pivotal role in the regulation of
      cell proliferation in higher eukaryotes. We used DNA microarrays and cell lines
      containing either inducible E2F-1 or inducible E2F-3 to identify novel E2F target
      genes. Our data indicate that E2F up-regulates the expression of genes not
      previously described as E2F target genes. A number of these E2F-regulated genes
      are involved in DNA replication, DNA repair and mitosis. These results suggest
      that E2F affects cell cycle progression both at S phase and during mitosis.
      Furthermore, our findings indicate that E2F-dependent gene activation may
      contribute to the cellular response to DNA damage.

PMID- 11821957
TI  - Repression of in vivo growth of Myc/Ras transformed tumor cells by Mad1.
AB  - The Myc/Max/Mad network of transcriptional regulatory proteins plays an essential
      role in cell proliferation, growth, apoptosis, and differentiation. Whereas Myc
      proteins affect cell cycle progression positively, Mad proteins are negative
      regulators of cell proliferation. It has been shown in several in vitro systems
      that Mad proteins antagonize c-Myc functions. In this report we describe the
      inhibition of tumor cell outgrowth in vivo by Mad1 expression. Transformed cell
      lines were generated by co-transfection of c-myc, c-H-ras, and a chimeric mad1ER
      construct into primary rat embryo cells (MRMad1ER cells). Activation of Mad1 by 4
      Hydroxy-Tamoxifen (OHT) resulted in abrogation of telomerase activity, reduced
      cloning efficiency, and decreased proportion of cells in S phase. Injection of
      MRMad1ER cells into syngenic rats induced aggressively growing tumors after a
      short latency period. This tumor growth was inhibited by OHT-treatment of
      animals, with the extent of inhibition correlating with the amount of OHT
      injected. No effect of OHT on tumor growth was observed with similarly
      transformed Myc/Ras cell lines which did not express Mad1ER. These data
      demonstrate that Mad1 is able to suppress Myc/Ras-mediated transformation under
      in vivo conditions.

PMID- 11821958
TI  - An unexpected biochemical and functional interaction between gp130 and the EGF
      receptor family in breast cancer cells.
AB  - Oncostatin M (OSM), an interleukin-6 type cytokine, acts via the gp130 signaling
      receptor to inhibit proliferation and induce differentiation of breast cancer
      cells. EGF, a mitogen for breast cells, signals via EGFR/ErbB tyrosine kinase
      receptors which are implicated in breast cancer pathogenesis. Here we show
      paradoxically that EGF enhanced the OSM-induced inhibition of proliferation and
      induction of cellular differentiation in both estrogen receptor positive and
      negative breast cancer cells. This functional synergism was also seen with
      heregulin but not SCF, PDGF or IGF-1, indicating that it was specific to EGF
      related growth factors. Immunoprecipitation experiments revealed that gp130 was
      constitutively associated with ErbB-2 and ErbB-3. There was a similar association
      between the OSMRbeta and ErbB-2. Furthermore, EGF unexpectedly induced tyrosine
      phosphorylation of gp130. We show that OSM induced phosphorylation of STAT3. Both
      OSM and EGF activated the p42/44 MAP kinases, but while the MEK inhibitor,
      PD98059, ablated the OSM-induced inhibition, it only partially ablated the
      inhibitory effects of OSM plus EGF. Thus, we have demonstrated that the receptors
      and signalling pathways of two apparently unrelated growth factors were
      intimately linked, resulting in an unexpected biological effect. This provides a
      new mechanism for generating signalling diversity and has potential clinical
      implications in breast cancer.

PMID- 11821959
TI  - Global gene expression profiling in Barrett's esophagus and esophageal cancer: a
      comparative analysis using cDNA microarrays.
AB  - In order to identify and contrast global gene expression profiles defining the
      premalignant syndrome, Barrett's esophagus, as well as frank esophageal cancer,
      we utilized cDNA microarray technology in conjunction with bioinformatics tools.
      We hybridized microarrays, each containing 8000 cDNA clones, to RNAs extracted
      from 13 esophageal surgical or endoscopic biopsy specimens (seven Barrett's
      metaplasias and six esophageal carcinomas). Hierarchical cluster analysis was
      performed on these results and displayed using a color-coded graphic
      representation (Treeview). The esophageal samples clustered naturally into two
      principal groups, each possessing unique global gene expression profiles. After
      retrieving histologic reports for these tissues, we found that one main cluster
      contained all seven Barrett's samples, while the remaining principal cluster
      comprised the six esophageal cancers. The cancers also clustered according to
      histopathological subtype. Thus, squamous cell carcinomas (SCCAs) constituted one
      group, adenocarcinomas (ADCAs) clustered separately, and one signet-ring
      carcinoma was in its own cluster, distinct from the ADCA cluster. We conclude
      that cDNA microarrays and bioinformatics show promise in the classification of
      esophageal malignant and premalignant diseases, and that these methods can be
      applied to small biopsy samples.

PMID- 11821961
TI  - Breakpoints in the ataxia telangiectasia gene arise at the RGYW somatic
      hypermutation motif.
AB  - The mature sporadic T-cell malignancy, T-cell prolymphocytic leukemia (T-PLL) is
      remarkable for frequently harbouring somatic mutations of the Ataxia
      Telangiectasia (A-T) gene, ATM. Because some data suggest ATM is frequently
      rearranged in T-PLL, it was decided to investigate such rearrangements in detail
      by cloning breakpoints. Among 17 T-PLL tumour samples, three rearrangements were
      detected by Southern blotting. Two cases harboured a unique type of intragenic
      duplication in which breakpoints arose at the consensus sequence RGYW/WRCY. The
      third case harboured a large deletion terminating within the ATM gene. Also, 13 T
      cell acute lymphoblastic leukemia (T-ALL) samples were examined and one sample
      harboured a deletion- insertion with the RGYW motif at the breakpoint in ATM.
      This is the first known deleterious mutation detected in ATM in T-ALL.
      Interestingly, the RGYW motif is the signal for a cell-cycle regulated DNA double
      strand break (DSB) that initiates somatic hypermutation of immunoglobulin and,
      probably, T-cell receptor genes. The structures of the ATM duplications suggest
      they may arise from an error in somatic hypermutation. We suggest that aberrant
      components of somatic hypermutation may contribute to the defective DSB repair
      characteristic of cancer.

PMID- 11821960
TI  - Somatic VHL gene deletion and point mutation in MEN 2A-associated
      pheochromocytoma.
AB  - Multiple endocrine neoplasia type 2 (MEN 2) is an inherited cancer syndrome that
      includes pheochromocytoma. Germline mutations in RET are responsible for MEN 2
      but the precise pathogenetic mechanisms of tumorigenesis are unknown. We have
      recently identified possible mechanisms of tumor formation in patients with MEN
      2A-related pheochromocytoma. Two of nine tumors investigated, however, did not
      reveal either of these mechanisms. In the present study, we therefore searched
      for other possible mechanisms underlying the pathogenesis of MEN 2A-related
      pheochromocytoma. Hereditary pheochromocytoma also occurs in patients with von
      Hippel-Lindau (VHL) disease, a syndrome consisting of tumors caused by
      inactivation of the VHL tumor suppressor gene. A subset of sporadic
      pheochromocytomas have somatic mutations in RET or VHL, suggesting that both
      genes contribute to pheochromocytoma pathogenesis in a subset of tumors. It is
      unknown, however, whether VHL gene alterations would be associated with
      tumorigenesis in hereditary, MEN 2-related pheochromocytoma. We therefore
      investigated four pheochromocytomas from patients with MEN 2A and RET germline
      mutations for the presence of allelic deletion and/or somatic mutation of the VHL
      gene. LOH analysis using the polymorphic markers D3S1038 and D3S1110 that map to
      the VHL gene locus 3p25/26, revealed evidence for somatic VHL gene deletion in
      all four MEN 2A-related pheochromocytomas. Mutation analysis of the VHL gene
      showed frameshift mutations in two tumors and a splice acceptor mutation in one
      tumor. The remaining tumor did show LOH but not mutation of the VHL gene. These
      results suggest that somatic genetic alterations of the VHL gene may play a role
      in the tumorigenesis of some MEN 2A-related pheochromocytomas.

PMID- 11821962
TI  - Homologous recombination induced by replication inhibition, is stimulated by
      expression of mutant p53.
AB  - Cell cycle control, faithful DNA replication, repair and recombination are
      associated in a network of pathways controlling genome maintenance. In mammalian
      cells, inhibition of replication produces DNA breaks and induces RAD51-dependent
      recombination, in a late step. Here we examine whether the status of p53 affects
      this process in mouse L-cells containing a recombination substrate. We show that
      expression of the mutant (His175)p53 strongly stimulates recombination induced by
      aphidicolin, in a late step (kinetically related to the RAD51 step). Mutant p53
      stimulates recombination induced by the replication elongation inhibitors
      (aphidicolin, hydroxyurea and Ara-C) but is without effect on recombination
      induced by the initiation inhibitors (mimosine and ciclopirox olamine). We
      compared the impact of several p53 mutations showing different effects on the G1
      checkpoint and on recombination. We show that the mutant (Pro273)p53 protein,
      which does not alter the G1 checkpoint, strongly stimulates recombination induced
      by elongation inhibitors. These results show that p53 can act on recombination
      induced by replication arrest independently of its role in the G1 checkpoint. An
      action of p53 via the RAD51 pathway is discussed.

PMID- 11821963
TI  - Muscle stretching for treatment and prevention of contracture in people with
      spinal cord injury.
AB  - Contracture, or reduced joint mobility, is a common and disabling sequel of
      spinal cord injury. The primary intervention for the treatment and prevention of
      contracture is regular stretch to soft tissues. While the rationale for this
      intervention appears sound, the effectiveness of stretching has not been verified
      with well designed clinical trials. One recent randomised trial suggests there is
      no clinically worthwhile effect from a typical stretch protocol applied to spinal
      cord injured patients. Despite the negative results of this first trial, we argue
      that therapists should continue administering stretch for the treatment and
      prevention of contracture until the results of further studies emerge. To
      maximise the probability of attaining a clinically worthwhile effect, we suggest
      that therapists stretch soft tissues for long periods (at least 20 min, and
      perhaps for as long as 12 h a day). Practical suggestions are given on how to
      readily provide spinal cord injured patients with sustained stretch to key joints
      and muscle groups. Stretch is most likely to be effective if started before the
      onset of contracture. Soft tissues most at risk should be targeted, particularly
      if contracture is likely to impose functionally important limitations.

PMID- 11821964
TI  - Efficacy of specialist versus non-specialist management of spinal cord injury
      within the UK.
AB  - STUDY DESIGN: Retrospective outcome measurement study. OBJECTIVES: Spinal cord
      injury (SCI) represents a life changing multi-factorial event for persons
      sustaining this condition. There has been anecdotal evidence that some persons
      sustaining this condition in the UK have not been managed within one of the 11
      national specialist spinal injury units (SIU) but rather are managed in non
      specialist rehabilitation areas. This study aimed to ascertain if differences in
      outcome from health, functional and social perspectives exists between the two
      cohorts. SETTING: All participants had received rehabilitation within the UK
      National Health Service. METHOD: A sample of 800 participants were recruited from
      the database of the Spinal Injury Association (UK) to complete a postal, self
      reporting questionnaire ascertaining perceived outcome across all of these
      perspectives. RESULTS: Despite having more severe injuries, the SIU cohort
      demonstrated statistically significant improved outcomes in 10 out of 18 health
      outcomes, 16 out of 18 functional outcomes and five out of 10 social outcomes in
      comparison with the non-SIU cohort. CONCLUSION: This study provides the evidence
      that people with SCI are better managed through a specialist system. Should a
      like for like comparison have been made as regards severity (completeness) of
      injury, the likelihood is that the results would have been even more in favour of
      the SIU cohort. These results should encourage commissioners of health care and
      those working in trauma settings to ensure people with SCI are managed in a
      specialist spinal injury unit setting both nationally and internationally.

PMID- 11821966
TI  - Linkages between coping and psychological outcome in the spinal cord lesioned:
      development of SCL-related measures.
AB  - STUDY DESIGN: Cross-sectional. OBJECTIVES: To investigate relationships between
      coping and mental well-being with clinical relevance to spinal cord lesion (SCL).
      SETTING: The Gothenburg Spinal Injuries Unit in Sweden. METHODS: The study sample
      comprised 274 persons. From in-depth interviews, literature reviews, and the
      transactional theory of stress and coping, items reflecting coping and
      psychological outcome, respectively were generated. Principal components factor
      analysis, multi-trait analysis, and structural equation modelling were used.
      RESULTS: The coping scale comprised three factors: Acceptance (i.e. revaluation
      of life values); Fighting spirit (i.e. efforts to behave independently); Social
      reliance (i.e. a tendency towards dependent behaviour). The outcome scale
      included the factors: Helplessness (i.e. feeling perplexed, out of control and
      low self-esteem); Intrusion (i.e. bitterness and brooding); Personal growth (i.e.
      positive outcomes of life crisis). Acceptance showed a positive relation to
      Personal growth and was inversely related to both Helplessness and Intrusion.
      Fighting spirit had a weak negative association to Helplessness and a weak
      positive association to Personal growth. Social reliance was positively related
      to Helplessness and Intrusion. Only Social reliance showed any association to
      neurological status. Those lesioned 1-4 years reported more Helplessness,
      Intrusion, Social reliance, and less Acceptance than those lesioned >or=5 years.
      CONCLUSION: Coping is related to psychological outcome in SCL. Our situational
      coping measure may be a candidate to assess intervention effects.

PMID- 11821965
TI  - Gait analysis on the treadmill - monitoring exercise in the treatment of
      paraplegia.
AB  - STUDY DESIGN: A prospective study was performed to evaluate the gait training of
      seven consecutive spinal cord injured patients and 10 controls on a treadmill
      using instrumented gait analysis and video documentation. OBJECTIVES: To
      determine whether it is possible to maintain gait motion within physiological
      limits during treadmill training. SETTING: Primary and secondary care unit for
      spinal cord injury, Heidelberg, Germany. METHODS: Treadmill training was
      instituted as early as possible. Gait analysis was performed when the patients
      were stable enough to walk without manual aid from therapists and enough
      endurance to allow measurements. A control group of healthy volunteers were
      examined as well. Video documentation and a camera system using passive markers
      were employed. RESULTS: Treadmill training started with weight reduction of 25%
      of bodyweight (18 (0-35) kg), maximum walking speed 0.28 (0.15-0.7) m/s and
      maximum walking duration 4.7 (3-7) min. At the end of the training, weight
      reduction decreased to 9.3 (0-20) kg, maximum walking speed increased to 0.67
      (0.23-1.1) ms with a maximum walking duration of 11 (8-15) min. 3-D motion
      analysis of hip, knee and ankle demonstrated joint excursions almost entirely
      within the limits of normal gait. Exceptions were due to fixed contractures.
      CONCLUSIONS: Our data suggests that it is possible to perform early gait training
      on a treadmill with no supportive orthoses within the physiologic range of joint
      motion. The risk for repetitive stress injuries or other negative effects is low.

PMID- 11821967
TI  - Augmentation ileocystoplasty in patients with neurogenic bladder due to spinal
      cord injury or spina bifida.
AB  - STUDY DESIGN: Retrospective analysis of augmentation ileocystoplasty for
      neurogenic bladder. OBJECTIVES: To analyze the effects and complications of
      augmentation ileocystoplasty in patients with neurogenic bladder due to spinal
      cord injury (SCI) or spina bifida retrospectively. SETTING: Department of
      Urology, Kanagawa Rehabilitation Hospital, Japan. METHODS: We have treated 11
      patients with neurogenic bladder due to SCI and 10 patients with spinal bifida
      with augmentation ileocystoplasty since 1989. The purpose of the treatment was to
      stop vesicoureteral reflux (VUR) and/or amelioration of urinary incontinence. In
      17 of 21 cases, the antireflux operation was received simultaneously. All cases
      performed clean intermittent self catheterization postoperatively. RESULTS:
      Urinary incontinence improved in all cases and only transient recurrence of VUR
      was observed in the follow-up term. Complications occurred in patients with SCI,
      but they could be treated conservatively. CONCLUSION: Augmentation
      ileocystoplasty is a good treatment option for contracted bladder or VUR, which
      occurs in patients with neurogenic bladder.

PMID- 11821968
TI  - Electrical stimulation of abdominal muscles for control of blood pressure and
      augmentation of cough in a C3/4 level tetraplegic.
AB  - OBJECTIVES: Evaluation of a FES (Functional Electrical Stimulation) device for
      the relief of postural hypertension and augmentation of cough in a C3 ventilator
      dependent tetraplegic. STUDY DESIGN: A single case study. SETTING: A supra
      regional spinal unit in the UK. METHOD: A dual channel stimulator was designed
      that allowed selection and initiation of two predetermined stimulation
      intensities using a chin controlled joystick. Two sets of 70 mm diameter
      electrodes were placed either side of the abdomen. Approximately 80 mA, 300
      micros, 40 Hz was required for assisted cough while about 40 mA was required for
      maintenance of blood pressure. After eating, the lower level stimulus is self
      administered every 3 to 5 min gradually increasing the time between groups of
      burst to once every hour after 90 min. RESULTS: Following eating, a blood
      pressure of 60/45 mmHg was recorded. After five 1 s bursts of stimulation in
      quick repetition, this was increased to 133/92 mmHg. After 2 min blood pressure
      had fallen to 124/86 mmHg and to 93/66 after a further 4 min. The electrical
      stimulation was then repeated, returning the blood pressure to the previous
      higher level. Measurement of peak expiratory flow showed an increase from 275
      l/min for an unassisted cough to 425 l/min when using the device. CONCLUSION: The
      device is used every day. The user is now independent in coughing function and no
      longer requires suction or manual assistance. Maintenance of blood pressure has
      significantly improved his quality of life.

PMID- 11821969
TI  - A great misfortune: second traumatic spinal cord injury.
AB  - OBJECTIVE: A second and a separate traumatic spinal cord injury, which results in
      neurological deterioration, is very rare. In this report we describe a patient
      who became tetraplegic after sustaining a second spinal trauma. CASE REPORT: A 27
      year-old female had a C(7)-T(1) dislocation after a motor vehicle accident. She
      was neurologically intact and she had undergone a posterior fusion between C(6)
      T(2). She made a complete recovery. Eight months after her initial trauma, she
      sustained a second motor vehicle accident causing a C(5) burst fracture.
      CONCLUSION: Second traumatic spinal cord injury is a rare entity. Motor vehicle
      accidents are the most common cause of this type of injury. Whatever the
      treatment strategy is, the best treatment modality for traumatic spinal cord
      injury is prevention.

PMID- 11821970
TI  - Intramedullary teratoma of the spine: report of two adult cases.
AB  - STUDY DESIGN: Two case reports of intramedullary teratoma in the spinal cord of
      adults, and a review of the literature. OBJECTIVE: To investigate and describe
      unusual cases of spinal teratoma using MRI to define features that may be used to
      avoid misdiagnosis. SETTING: A department of orthopedic surgery in Japan.
      METHODS: One patient, a 37-year-old woman, was referred because of gait
      disturbance. She was evaluated by myelography, CT scan with myelography, and MRI.
      T12 through L1 laminoplasty was performed and the tumor was subtotally removed.
      The other patient, a 56-year-old man, was referred because of muscle weakness and
      sensory disturbance. MRI revealed multiple spinal tumors. C4 through C6
      laminoplasty and T12 through L2 laminoplasty were performed, and the tumors in
      these regions were subtotally removed. RESULTS: In Case 1, the postoperative
      course was excellent, and histological examination of the resected specimen
      revealed a spinal teratoma consisting of ectodermal and mesodermal elements. In
      Case 2, the symptoms were resolved after surgery, and ectodermal, mesodermal and
      endodermal elements were revealed. CONCLUSIONS: Although intramedullary teratomas
      are very rare in adults, they need to be considered in differential diagnosis.

PMID- 11821971
TI  - Transverse syndrome as the dominant feature of solitary cervical plasmocytoma
      with dissemination.
AB  - STUDY DESIGN: A case report of transverse syndrome secondary to compression from
      an intravertebral plasmocytoma. OBJECTIVES: To report a rare case of cervical
      cord compression. SETTING: Vienna, Austria. CASE REPORT: A 47-year-old man
      presented with pain over the left scapula and subsequent development of pain and
      sensory disturbance. Investigations showed that the entire C7 vertebra was
      affected by a plasmocytoma. Decompression was carried out but no stabilisation of
      the spinal column was performed. Seven days after surgery the patient became
      paraplegic. Chemotherapy produced no improvement. CONCLUSION: Transverse syndrome
      may be a dominant feature of plasmocytoma and may resolve after immediate
      decompression but may recur if the spinal column is not stabilised.

PMID- 11821972
TI  - Clopidogrel and recurrent severe haematuria in a patient with paraplegia.

PMID- 11821974
TI  - A simplified cataract grading system.
AB  - A simplified method for grading the presence and severity of different cataract
      types is needed for field use in assessment of the magnitude of the cataract
      problem. A cataract grading system was developed by a panel of experts with the
      objective of making available a simple system for use with a slit lamp to allow
      for the reliable grading of the most common forms of cataract by relatively
      inexperienced observers. Three levels, reflecting progressive severity, for
      grading of nuclear, cortical and posterior subcapsular (PSC) cataract were
      included in the classification; three standard photos were used for grading
      nuclear cataract. Field evaluation from four different sites indicated very good
      to fair interobserver agreement with the use of this system following minimal
      training of residents in ophthalmology at each site. Further testing of this
      system is warranted. The WHO simplified cataract grading system should allow for
      the obtaining of comparable data across countries based on field assessment of
      the most common forms of cataract.

PMID- 11821975
TI  - Rapid assessment of trachoma in Hainan Province, China: validation of the new
      World Health Organization methodology.
AB  - This study was undertaken to validate a WHO methodology for the rapid assessment
      of trachoma. Fourteen villages were chosen by random sampling in two counties in
      Hainan Province, China. For the rapid assessment, trichiasis patients were
      identified, 50 children ages 1-10 years were examined for active trachoma, and
      information was collected on community access to services and community risk
      factors. To validate the methodology, a prevalence survey was undertaken
      simultaneously in the same villages. For the prevalence survey, 2428 people from
      1606 households in the 14 villages were chosen by random sampling. Very little
      active trachoma was found by either method, although the rates of trichiasis were
      more substantial. Ranking of the villages by the two methods for trichiasis was
      highly correlated (Spearman's correlation coefficient = 0.60, p = 0.02). For
      active trachoma, the Spearman's correlation coefficient for the ranking of
      villages by the two methods was 0.40 and not significant (p = 0.14), suggesting
      that a correlation this close may have been seen by chance alone. The
      observational data showed all the villages to be at risk of active trachoma (due
      to poor environmental hygiene conditions), suggesting that this aspect of the WHO
      methodology overestimates the risk for active trachoma. We conclude that, with
      the exception of the community assessment of risk, this rapid assessment
      methodology is a valid tool for the assessment of trichiasis and possibly of
      active trachoma in rural communities, although the level of active trachoma in
      this study was too low to effectively validate that aspect of the methodology.

PMID- 11821976
TI  - The Flies and Eyes project: design and methods of a cluster-randomised
      intervention study to confirm the importance of flies as trachoma vectors in The
      Gambia and to test a sustainable method of fly control using pit latrines.
AB  - The Flies and Eyes project is a community-based, cluster-randomised, intervention
      trial based in a rural area of The Gambia. It was designed to prove whether flies
      are mechanical vectors of trachoma; to quantify the relative importance of flies
      as vectors of trachoma and to test the effectiveness of insecticide spraying and
      the provision of latrines in trachoma control. A total of 21 clusters, each
      composed of 300-550 people, are to be recruited in groups of three. One cluster
      from each group is randomly allocated to receive insecticide spraying, one to
      receive pit latrines and the remaining to act as a control. The seven groups of
      clusters are recruited on a step-wise basis separated by two months to aid
      logistics and allow all seasons to be covered. Standardised, validated trachoma
      surveys are conducted for people of all ages and both sexes at baseline and six
      months post intervention. The Muscid fly population is monitored using standard
      traps and fly-eye contact is measured with catches of flies direct from
      children's faces. The Flies and Eyes project has been designed to strengthen the
      evidence base for the 'E' component of the SAFE strategy for trachoma control.
      The results will assist programme planners and country co-ordinators to make
      informed decisions on the environmental aspects of trachoma control.

PMID- 11821977
TI  - The National Blindness and Low Vision Prevalence Survey of Bangladesh: research
      design, eye examination methodology and results of the pilot study.
AB  - PURPOSE To describe the research design and eye examination protocol of The
      National Blindness and Low Vision Prevalence Survey of Bangladesh and to present
      the main results of the rural pilot study. METHODS A thorough description of the
      sampling strategy, eye examination protocol and operational definitions are
      presented. Multi-stage stratified (rural/urban) cluster random sampling, with
      probability proportional-to-size procedures, will be used for selection of a
      cross-sectional, nationally representative sample (12,900 subjects) of the
      population aged > or = l30 years. Each subject will be tested for visual acuity,
      auto-refracted and undergo optic disc examination. Those with <6/12 visual acuity
      in either eye will be re-tested with their refractive correction, dilated and
      examined for anterior and posterior segment disease. A preliminary, separate
      rural pilot survey sample was conducted according to the eye examination
      procedures, with results reported herein. RESULTS Two-hundred-and-four (73.1%) of
      279 eligible subjects were examined for the rural pilot. Forty-eight persons had
      presenting visual acuity worse than 6/12 in either eye. The presenting visual
      acuity of the better eye was used to group the subjects into the following WHO
      categories (brackets enclose the number of subjects after refractive correction):
      Blind: 4 [4]; Visually impaired: 29 [14]; Sighted: 171 [186], of whom 3 [3] were
      unilaterally blind. Cataract was the main cause of visual acuity of less than
      6/12, followed by refractive error, and age-related macular degeneration.
      CONCLUSIONS The pilot survey demonstrated that the proposed examination process
      for the main survey was both feasible and appropriate for the purposes of this
      study. Particular strengths of the pilot and subsequent main survey include the
      use of logMAR visual acuity testing and auto-refraction of all subjects. The
      pilot study reveals the burden of cataract and refractive error, which are two of
      the five diseases specifically targeted by the WHO global blindness initiative
      'Vision 2020'.

PMID- 11821978
TI  - From visual function deficiency to handicap: measuring visual handicap in Mali.
AB  - BACKGROUND/AIMS: Blindness is a major public health problem in developing
      countries, even though most could be prevented by relatively simple hygienic and
      medical interventions. Relatively few patients use the quality health care
      services available, despite their low cost, due to problems of access or socio
      cultural barriers. This health services research project stressed the need for
      measurement of subjective self-perceived health. The objectives of this study
      were twofold: a) To translate, adapt and integrate the cultural context found in
      Mali and validate two instruments for measuring, respectively, perceived vision
      and quality of life. b) To study the relationship between these variables and
      visual deficiencies by gender. METHODS: The perceived vision and quality of life
      questionnaires were based on a translation of the Aravind questionnaire, adapted
      to Mali. The resulting perceived vision questionnaire comprises 13 questions,
      grouped according to five subscales (global vision, visual perception, sensory
      adaptation, visual field and depth perception). Furthermore, the 13 questions on
      quality of life were grouped into four subscales (personal care, mobility, social
      life and psychological). For both questionnaires, a global score could be
      computed. These two questionnaires were administered to a representative sample
      of 203 subjects with impaired vision, aged over 40, in a rural area in Mali.
      RESULTS: The acceptability of the questionnaires was good (1% missing data). The
      convergent validity was adequate for all but one subscale (psychological). The
      discriminate validity is acceptable for three of the six subscales where
      measurement can be made (visual perception, personal care, mobility). The
      Cronbach alpha coefficients indicate good reliability for the global scores.
      CONCLUSIONS: Analysis of mean results confirms the validity of the International
      Classification of Disease (ICD) definition of blindness (seeing less than 0.05
      results in a steep decrease in quality of life). Moreover, blindness affects the
      quality of life of women more severely than that of men; this may be related to
      the availability of social support.

PMID- 11821980
TI  - Corneal epithelial VEGF and cytochrome P450 4B1 expression in a rabbit model of
      closed eye contact lens wear.
AB  - PURPOSE: The similar and overlapping activity of VEGF and the potent corneal
      derived angiogenic eicosanoid 12(R)-HETrE calls for a study of the temporal
      relationship in the expression of these two autocoids. Since recent evidence
      suggests that hypoxia induces the expression of a CYP4B1 mRNA which might be
      involved in the conversion of arachidonic acid to 12(R)-HETrE, we determined its
      time-dependent expression and correlated it to that of VEGF mRNA in the rabbit
      model of closed eye contact lens-induced injury. METHODS: Rabbit eyes were fitted
      with contact lenses followed by a silk suture tarsorrhaphy. The anterior surface
      was analyzed at 2-, 4- and 7-days by slit lamp biomicroscopy, subjective
      inflammatory scoring and corneal pachymetry. Corneal epithelium was scraped and
      CYP4B1 and VEGF mRNA levels were measured by Southern hybridization of RT-PCR
      products amplified from a single cornea with specific primers. RESULTS: Corneal
      thickness and inflammatory scores increased in a time dependent manner in the
      model of closed eye contact lens induced hypoxic injury. Corneal epithelial
      CYP4B1 and VEGF mRNAs, as well as the production of the angiogenic eicosanoid, 12
      HETrE, increased in a time-dependent manner and correlated with the in situ
      inflammatory response. CONCLUSIONS: The present study documents the increased
      expression of CYP4B1 isoform in the corneal epithelium during hypoxic injury in
      vivo. It also demonstrates the presence of VEGF mRNA in the corneal epithelium
      and its increased expression in this model of hypoxic injury. All together, the
      results of this study raise the possibility of interaction between these
      autocoids, VEGF and CYP4B1-12(R)-HETrE, in mediating the neovascularization
      response induced by the prolonged hypoxic state brought about by closed eye
      contact lens wear.

PMID- 11821981
TI  - Rod outer segments mediate mitochondrial DNA damage and apoptosis in human
      retinal pigment epithelium.
AB  - PURPOSE: To investigate the interrelationships between DNA damage, mitochondrial
      activity, and apoptosis in retinal pigment epithelial cells (RPE) after exposure
      to rod outer segments (ROS). METHODS: After incubation of cultured human RPE with
      ROS, mitochondrial redox function was evaluated from MTT reduction. Mitochondrial
      (mt) and nuclear (n) DNA damage were determined by quantitative polymerase chain
      reactions (QPCR). Apoptotic RPE cells were detected by binding of annexin V to
      phosphatidyl serine (PS) using fluorescence microscopy. The expression of the pro
      apoptotic proteins, p53 and p21(waf-1), and DNA repair enzymes,
      apurinic/apyrimidinic endonuclease (APE(ref-1)) and DNA polymerase beta (beta
      pol) were quantitatively determined by Western blotting analysis. RESULTS:
      Mitochondrial function decreased by 20 +/- 5% and annexin V immunofluorscent
      binding was enhanced after exposure of cells to physiological levels of ROS (3.8
      x 10(6)cm(-2)) for 4 h. MtDNA was preferentially damaged after exposure to ROS
      with increased lesion frequencies of 1.49 +/- 0.37 and 2.2 +/- 0.14 per 10 kb
      base pairs (bp), respectively after 5 and 7 h contact, compared to untreated
      controls (zero class damage). APE(ref-1)expression increased more than 340% above
      controls after exposure to ROS for 7 and 24 h. The expression of beta-pol in
      cultures increased 110% above controls after 24 h contact with the ROS. The
      expression of p53 and p21 in cells increased 100 and 38% above controls after 24
      h exposure to the ROS. CONCLUSIONS: Exposure of ROS to ROS induced mtDNA damage
      and dysfunction and activated nDNA repair pathways, which did not prevent
      apoptosis.

PMID- 11821982
TI  - Structural characterization and comparison of promoter activity of mouse and
      bovine interphotoreceptor retinoid-binding protein (IRBP) gene 5' flanking
      regions in WERI, Y79, chick retina cells, and transgenic mice.
AB  - PURPOSE: To determine the sequences of the mouse and bovine interphotoreceptor
      retinoid-binding protein (IRBP) 5' flanking regions and whether these 5' flanking
      regions contain functional IRBP promoter activity in multiple cell types using
      both quantitative and statistical analyses. METHODS: We sequenced the bovine and
      mouse 5' flanking regions of the IRBP gene and compared these sequences to the
      human gene sequence. To test for functional activity of this region, we used the
      same DNA construct, p1783, in four different cell types. Mobility shift, DNase
      footprints, and southwestern blots were used to determine where nuclear protein
      complexes bind the IRBP 5' flanking region. RESULTS: The 5' flanking regions of
      the bovine, human, and mouse IRBP genes exhibit sequence similarity in regions
      immediately adjacent to the start of transcription (roughly 350 bases in length)
      and also over a 220 base sequence about 1.25 to 1.50 kb upstream of the
      transcription start site. Two different statistical approaches showed that the
      IRBP 5' flanking region possesses promoter activity in four different cell types.
      By using mobility shift, DNase I-protection experiments, and southwestern
      blotting, a region of about 45 bases at position -300 was identified that
      specifically binds a protein from the nuclei of bovine retina and Y79 cells.
      CONCLUSIONS: Specific DNA binding events are an essential part of IRBP promoter
      activity. The conservation of sequences far upstream of the transcription start
      suggest that unknown physiological processes remain to be understood in IRBP
      transcriptional regulation.

PMID- 11821983
TI  - Is age-related macular degeneration associated with pinguecula or scleral plaque
      formation?
AB  - PURPOSE: To evaluate whether ocular changes indicating an increased exposure to
      UV irradiation are associated with the development of age-related macular
      degeneration (ARMD). METHODS: Using histology, we have investigated a possible
      association of ocular changes that might be attributed to actinic damage, namely
      pinguecula and scleral plaque, with findings of both atrophic and disciform ARMD.
      A total of 74 eyes, could be used for evaluation. RESULTS: Features of ARMD were
      present in 36 eyes (11 with disciform degeneration and 25 with an atrophic form).
      A pinguecula was identified in 36 eyes (small in 22 eyes, large in 14 eyes), and
      a scleral plaque was seen in 5 eyes. While scleral plaque showed an association
      with ARMD, there was no significant association between pinguecula and ARMD.
      CONCLUSIONS: Our results support the concept of solar radiation having an effect
      on the development of ARMD but also indicate that it is a multifactorial disease.

PMID- 11821984
TI  - Hypercholesterolemia induces leukocyte entrapment in the retinal microcirculation
      of rats.
AB  - PURPOSE: To evaluate leukocyte dynamics in the retinal microcirculation of
      hypercholesterolemic rats in vivo using acridine orange digital fluorography.
      METHODS: 18 male pigmented rats were divided into 3 groups according to their
      diet; (A) control diet (0.1% cholesterol) for 8 weeks, (B) control diet for an
      initial 4 weeks followed by a high-cholesterol (HC) diet (5% cholesterol) for
      another 4 weeks and (C) HC diet for 8 weeks. Leukocyte dynamics were observed
      with acridine orange digital fluorography. The diameter of major retinal vessels
      and the number of leukocytes trapped in the retina were evaluated quantitatively.
      RESULTS: Both groups B and C showed approximately 4-fold higher serum cholesterol
      levels than in group A. The diameters of retinal arteries and veins were not
      significantly different among the three groups. Also, no rolling leukocytes were
      observed in any of the groups. In the retinal microcirculation at 30 minutes
      after acridine orange injection, the density of trapped leukocytes in both groups
      B and C was significantly greater than in group A (23.19 +/- 2.13, 28.56 +/- 1.96
      and 13.67 +/- 1.45 cells/mm(2), respectively, p < 0.01). Furthermore, group C
      exhibited a significantly greater number of trapped leukocytes than in group B (p
      < 0.01). CONCLUSION: Enhanced leukocyte entrapment in the retinal
      microcirculation was induced in the early stage of hypercholesterolemia.
      Entrapment was increased as the period of hypercholesterolemia was prolonged.
      Leukocyte accumulation in the retina may be an early vascular dysfunction leading
      to arteriosclerosis in hypercholesterolemia.

PMID- 11821985
TI  - Differential expression of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), beta
      actin and hypoxanthine phosphoribosyltransferase (HPRT) in postnatal rabbit
      sclera.
AB  - PURPOSE: GAPDH, beta-actin, HPRT and 18S rRNA are constitutively expressed in all
      mammalian cells. In accordance with the nature of invariant control, these genes
      have been used to standardize genes of interest in expression studies. Recent
      studies have suggested that GAPDH, beta-actin and HPRT in special situations may
      come under temporary regulatory control, but that 18S rRNA may be more likely to
      remain constitutive. However, little is known about the quantitative expression
      of these genes in fibroblasts and in particular during early postnatal
      development, a time of rapid changes in cell metabolism. In this study we have
      examined the differential expression of these genes in association with scleral
      development from an early postnatal age up to young adult status. METHODS: GAPDH,
      beta-actin, HPRT, and 18S rRNA gene expression were analyzed in the rabbit sclera
      from 1 day to 8 weeks postnatally by real-time, comparative PCR. RESULTS: Real
      time PCR analysis showed that the expression levels of GAPDH, beta-actin, and
      HPRT were higher in the first postnatal week and then declined. However, from 2
      to 8 weeks, the mRNA levels of these three genes underwent significant variations
      (P < 0.01) in their levels of expression. In contrast, the expression level of
      18S rRNA showed no significant variation (P >or= 0.5) over this time period.
      Conclusions. The present study shows that GAPDH, beta actin and HPRT gene were
      differentially expressed in early postnatal scleral development. It also suggests
      that these gene products could be implicated in the developmental process and
      have a crucial role in the early postnatal period. This study demonstrates that
      18S rRNA may be preferable to normalize genes of interest in studies of early
      development.

PMID- 11821986
TI  - The ex vivo wettability of soft contact lenses.
AB  - PURPOSE: To investigate the ex vivo wettability of Etafilcon A contact lenses
      over an eight hour period of wear and observe the influence of surfactant pre
      treatment. METHODS: Etafilcon A hydrogel lenses, comprising poly[2-hydroxyethyl
      methacrylate-co-methacrylic acid] and 58% water, were soaked for 12 hours in
      either 0.9% saline (control) or a 1% aqueous solution of poloxamine 1107
      (treated). The advancing and receding contact angles were subsequently determined
      ex vivo after various periods of wear in six adapted contact lens wearers using a
      single-blind, randomised protocol. Contact angles were measured with a dynamic
      contact angle tensiometer, using the Wilhelmy plate technique. Patient comfort
      scores were recorded and the static surface tensions of the probe fluids
      assessed. RESULTS: Control lenses exhibited no change in wetting angles over
      time, indicating a lack of surface modification by components within the tear
      film. Treated lenses exhibited a significantly reduced advancing angle (p <
      0.001) and hysteresis angle (p < 0.001) when compared with control lenses. In
      addition, treated lenses were consistently rated as being more comfortable than
      control lenses (p = 0.04). CONCLUSIONS: This study has shown clearly that new
      Etafilcon A lenses do not exhibit significant changes in wettability during the
      initial four hour wearing period. Pre-treatment of such lenses with a polymeric
      surfactant results in wetting of the lenses due to the adsorption of surfactant.
      The surfactant is retained by the lens for at least eight hours of wear,
      resulting in significant improvements in subjective comfort, especially over the
      first 30 minutes of wear.

PMID- 11821987
TI  - The effectiveness of tobramycin and Ocuflox in a prophylaxis model of
      Staphylococcus keratitis.
AB  - PURPOSE: To determine the effectiveness of prophylactic antibiotic treatment
      prior to intra-corneal infection with Staphylococcus aureus. METHODS: One topical
      drop of Tobrex (0.3% tobramycin), tobramycin (0.3%) in the Tobrex vehicle with
      0.05% dodecyl maltoside (DDM)/4.0% hydroxypropylmethycellulose (HPMC), Ocuflox
      (0.3% ofloxacin) or DDM/HPMC vehicle were applied to rabbit eyes at one or five
      hours prior to injection of bacteria. Approximately 500 colony-forming units
      (CFU) of S. aureus strain 8325-4 were injected into the corneal stroma. Rabbits
      were sacrificed five hours after infection and corneal homogenates were cultured
      to determine the number of colony forming units (CFU) per cornea. RESULTS:
      Rabbits treated at five hours prior to infection with tobramycin-DDM/HPMC reduced
      the bacterial load by approximately 2.4 log CFU/cornea as compared to the
      untreated control (3.47 +/- 0.98 vs. 5.71 +/- 0.14 log CFU/cornea, respectively;
      P = 0.0010); however, Ocuflox, Tobrex, or DDM/HPMC vehicle did not significantly
      reduce the log CFU (P >or= 0.4837). Rabbits treated at 1 hour prior to infection
      with Ocuflox or tobramycin-DDM/HPMC had significantly reduced CFU/cornea (1.31 +/
      0.86 and 0.48 +/- 0.31 log CFU/cornea, respectively) as compared to the
      untreated group (5.71 +/- 0.14 log CFU/cornea; P <or= 0.0001). Neither Tobrex nor
      the DDM/HPMC vehicle significantly reduced the CFU/cornea compared to the
      untreated group (P >or= 0.2312). CONCLUSIONS: This pre-treatment model of
      Staphylococcus keratitis quantitatively measured the prophylactic effectiveness
      of topical antibiotic formulations. An important finding was that a tobramycin
      DDM/HPMC formulation was highly effective as a prophylactic medication.

PMID- 11821988
TI  - Interleukin-18 expression and modulation in human corneal epithelial cells.
AB  - PURPOSE: The interferon-gamma-inducing factor Interleukin-18 (IL-18) is a
      recently described cytokine that appears to have multiple important pro
      inflammatory effects including the induction of interferon-gamma (IFN-gamma) by
      activated T-cells. The expression of IL-18 by human cornea has not been
      previously reported. In the present study, we examine the possibility that human
      corneal epithelial cells are capable of producing this leukocyte-activating
      factor which may play an important role in IFN-gamma-dependent inflammation
      responses in the cornea. METHODS: Northern blot analysis and ELISA were used to
      investigate the in vitro expression of IL-18 mRNA and protein respectively in
      primary (HCEC) and transformed human corneal epithelial cells (HCET). To
      determine if IL-18 expression was modulated by pro-inflammatory mediators, cells
      were treated with lipopolysaccharide (LPS), phorbol 12-myristate 13-acetate (PMA)
      or synthetic double stranded RNA (poly dI : dC). IL-18 bioactivity was determined
      in a leukocyte interferon-gamma induction assay and IL-18 was immunolocalized in
      whole human cornea by immunohistochemistry using a specific anti-IL-18 antibody.
      RESULTS: IL-18 mRNA and bioactive protein was constitutively expressed by human
      corneal epithelial cells and upregulated by PMA, LPS and poly dI : dC. The
      constitutive expression of IL-18 protein immunoreactivity was also demonstrated
      in the epithelial cells of whole human cornea tissue. CONCLUSIONS: This is the
      first study demonstrating that corneal epithelial cells are capable of producing
      the IFN-gamma inducing factor IL-18. Increased bioactive corneal IL-18 production
      can be induced by a number of pro-inflammatory agents and may play an important
      role in initiating gamma-interferon-mediated inflammatory responses in the
      cornea.

PMID- 11821989
TI  - Differential expression analysis by gene array of cell cycle modulators in human
      corneal epithelial cells stimulated with epidermal growth factor (EGF),
      hepatocyte growth factor (HGF), or keratinocyte growth factor (KGF).
AB  - PURPOSE: To identify and differentiate cell cycle and differentiation genes that
      are up-regulated or down-regulated in human corneal epithelial cells in response
      to alternative epithelium-modulating cytokines epidermal growth factor (EGF),
      hepatocyte growth factor (HGF) or keratinocyte growth factor (KGF). METHODS:
      Primary cultures human corneal epithelial cell (HCE) were treated with 25 ng/ml
      of EGF, 25 ng/ml HGF, 25 ng/ml KGF, or vehicle for 8 hours. Complementary DNA
      (cDNA) probes were synthesized from total cellular RNA isolated from the HCE
      cells. The cDNA probes were hybridized to the Atlas human cell
      cycle/differentiation array membrane. RNAse protection assay was used to confirm
      up-regulation of the serine/threonine-protein kinase PITALRE gene by EGF, KGF,
      and HGF. RESULTS: The expression of one hundred and eleven cell cycle and
      differentiation genes was monitored with the gene array system. It was found that
      these epithelial cell-modulating cytokines shared similar effects on some of the
      cell cycle and differentiation genes that were monitored, but had specific
      effects on some cytokines. Up-regulation of PITALRE gene expression was confirmed
      using RNAse protection assay. CONCLUSION: EGF, HGF and KGF had differential
      effects on cell cycle- and differentiation-related gene expression in corneal
      epithelial cells. For example, all three mitogenic growth factors up-regulated
      the expression of cyclin D1 (BCL-1 oncogene) and serine/threonine-protein kinase
      PITALRE in the primary cultured human corneal epithelial cells. However, EGF and
      KGF, but not HGF, up-regulated expression of the E2F-1 pRB-binding protein gene.
      Thus, while these three epithelial mitogens have similar effects on many genes
      that were analyzed, important differences were noted that may relate to differing
      effects of these growth factors on corneal epithelial cells. Studies to analyze
      the significance of the identified differences among these growth factors are in
      progress.

PMID- 11821990
TI  - [The "Adjusted Annual Index" (aJaX): A proposal for the use of the IMPP results
      in the evaluation of teaching at German medical faculties].
AB  - BACKGROUND AND OBJECTIVE: Teaching evaluations should create an incentive to
      improve academic teaching quality. Teaching also gains importance in the
      performance-oriented allocation of resources. The results of the country wide
      written examinations conducted by the Federal Institute for Medical and
      Pharmaceutical Examination Questions (IMPP) are obvious indicators for purposes
      of comparative evaluation. However, a comparison of medical faculties is
      confounded by heterogeneous proportions of students in the so called "reference
      group" This group includes students who attend their examinations within the
      regular duration of study; these candidates achieve significantly better results
      than other students. This contribution describes a comparative educational
      achievement index (aJaX) adjusting for the varying proportions of students in the
      reference group. MATERIAL AND METHODS: The IMPP publishes the results of the
      examinations, disaggregated according to faculties, type of examination,
      examination subjects, examination semester and membership in the reference group.
      Aggregation of the semi-annual data to annual data leads to equal treatment of
      faculties with different admittance regulations. The proportion of students in
      the reference group is taken into account by calculating an adjusted annual index
      (aJaX) which compares the observed result of the respective medical faculty with
      the result one would expect if the average (federal) outcome would apply to a
      faculty with an equal proportion of students in the reference group (i. e.
      indirect standardisation). RESULTS: The success rates of the faculties, as
      defined by the adjusted annual index aJaX, lie with a few exceptions in the
      interval between 0.95 and 1.05 during the years 1994 to 2000. The results of the
      second year examinations demonstrate the largest variance. Over time strong
      deviations rarely occur. These stable results are not observed with the
      frequently used reference-autumn-index (ReX), which only takes into consideration
      the results of the reference groups in the autumn examinations. Temporal trends
      therefore become more clearly visible in the aJaX. The faculties of the new
      federal states show a clear upward trend in the analysed period. CONCLUSIONS: The
      results of the medical faculties in the uniform examinations can be compared
      using an adjusted annual index aJaX. Advantages of the aJaX lie in its stability
      and neutrality, which are obtained by the annual aggregation of data and the
      reference group adjustment. The low degree of scatter emphasises a high
      standardisation in academic medical teaching. However, the aJaX measures only one
      output of teaching. For the assessment of teaching efficiency in the sense of an
      input/output relation, inputs must also be taken into account, such as the final
      school grades of the entering and transferring students.

PMID- 11821991
TI  - [Wound botulism after drug injection].
AB  - CLINICAL PRESENTATION: A 32-year old male drug user presented with diplopia,
      ataxia and general weakness. The patient had abscesses on arms and legs at
      injection sites, bilateral ptosis, a bifacial weakness, nasal speech, severely
      reduced ability to raise his arms and a positive Trendelelenburg sign with normal
      motor neuron reflexes and normal sensation. CLINICAL AND LABORATORY TESTS: The
      haematological values indicated a hypochromic, microcytic anaemia (12,1 mg/dl), a
      slight leuko (10,8 G/L) - and thrombocytosis (582G/l) with elevated erythrocyte
      sedimentation rate (74 mm/h), and a reduced prothrombin time (67%). The HIV test
      was negative. The MRI scan of the brain and the bacterial, serological and
      cytological results of a lumbar puncture were normal. In the bloodculture no
      bacterial growth and no botulinum toxin was found. In a culture of the wound
      material grew coagulase-negative staphylococcus and Clostridium perfringens,
      diagnosed with PCR. The serum anti-acethylcholine antibodies were negative. The
      motor-nerve conduction test with repetitive stimulation of the ulnari nerve with
      a 3 Hz trigger showed no change in the amplitude, while a 20 Hz trigger showed an
      increment up to 160 %. DIAGNOSIS, TREATMENT AND RESPONSE TO THERAPY: Another
      possible diagnosis was excluded through MRI, CSF and serum examination. The
      typical presentation of a rapidly progressive descending paralysis without loss
      of sensation and the typical motor-nerve conduction disorder of a presynaptic
      block established the diagnosis of wound botulism. This was treated immediately
      by surgical removal of wound debris, antitoxin- and penicillin therapy. After 28
      days the patient left the hospital with slight residual problems. He had been
      admitted to the intensive care unit for a short period only and intubation was
      not necessary at any time. CONCLUSION: After exclusion of any other possible
      diagnosis, it is possible to establish an early diagnosis of injection related
      wound botulism by its typical symptoms and signs. These are presented as wound
      abcesses at intramuscular drug injection sites together with rapidly progressive
      descending paralysis with preserved sensation. Treatment consists of surgical
      excision of wound debris combined with antitoxin and penicillin administration in
      order to prevent a possible build-up of residues. Early diagnosis and associated
      therapy overcome the necessity of intubation and prolonged intensive care.

PMID- 11821992
TI  - [Hyperuricemia and gout. Case report].

PMID- 11821993
TI  - [Hyperuricemia and gout--diagnosis].

PMID- 11821994
TI  - [Hyperuricemia and gout--treatment].

PMID- 11821997
TI  - [Internal quality management, institutional guidelines and "infection control". A
      comprehensive concept of control in hospitals].

PMID- 11821998
TI  - [Study of antibodies (ENA, ANA)].

PMID- 11821999
TI  - [Certificate of fitness for athletic divers].

PMID- 11822000
TI  - [Can left ventricular pathological hypertrophy in arterial hypertension be
      distinguished from physiological hypertrophy due to sports?].

PMID- 11822001
TI  - [Can left ventricular pathological hypertrophy in arterial hypertension be
      distinguished from physiological hypertrophy due to sports?].

PMID- 11822004
TI  - Gastroesophageal reflux disease and Barrett's esophagus.
AB  - Gastroesophageal reflux disease (GERD) is a common clinical problem. More
      frequent and extended acidic reflux episodes are characteristic of GERD, although
      substantial (nonacid) reflux per se is also observed in control individuals.
      Helicobacter pylori may protect some people from reflux disease, but others do
      not experience deterioration of GERD as a result of H. pylori eradication, for
      reasons so far unknown. Medical treatment, preferably with proton-pump
      inhibitors, is well established and is also recommended in endoscopy-negative
      forms of the disease, although the efficacy is less marked in comparison with
      erosive esophagitis. Surgery has emerged as an alternative to medical therapy,
      but the long-term results do not now appear to be as promising as was initially
      claimed. A number of new endoscopic techniques for the treatment of GERD have
      been developed, but the future for these is unclear. Barrett's esophagus develops
      in some patients with GERD for unknown reasons, and surveillance should be
      carried out in these patients due to the risk of subsequent malignant
      transformation. Several new approaches have been developed for detecting
      premalignant conditions, but these need to be investigated further. Ablative
      techniques are still under intensive investigation, and appear to be promising,
      at least in a subset of patients, although they are not devoid of major
      complications. Whether antireflux therapy, irrespective of the method used, can
      slow down the development of cancer is still an intriguing and clinically
      important question.

PMID- 11822005
TI  - Ulcer and gastritis.
AB  - The literature on peptic ulcer and gastritis in 2000 again focused on the topics
      of Helicobacter pylori, nonsteroidal anti-inflammatory drugs (NSAIDs), and
      gastric cancer. New diagnostic tests for H. pylori infection have been evaluated,
      and rescue therapies for failed H. pylori eradication have been tested. The
      causal relationship between H. pylori infection and nonulcer dyspepsia, gastric
      cancer, gastroesophageal reflux disease, and NSAID-related ulcers remained heated
      topics of debate. In 2000, landmark clinical trials and meta-analyses were
      published addressing these issues. The role of endoscopy in managing nonulcer
      dyspepsia was better defined. The role of H. pylori eradication in NSAID/aspirin
      users was reexamined in high-risk patients. Clinical benefit was finally
      confirmed for specific inhibitors of cyclooxygenase-2 (COX-2). The millennium
      year turned out to be a very important one in the advancement of knowledge in
      this field.

PMID- 11822006
TI  - Nonvariceal upper gastrointestinal bleeding.
AB  - Nonvariceal upper gastrointestinal bleeding (NVUGIB) remains an important cause
      of morbidity and mortality. The etiological role and the relative risk of
      nonsteroidal anti-inflammatory drugs (NSAIDs) in association with other clinical
      factors are the focus of several papers published in the last year. Data from
      studies that evaluate the interaction of NSAIDs with Helicobacter pylori suggest
      that there is a clear role for eradication in aspirin-related bleeding. Although
      the benefit of H. pylori eradication in nonaspirin NSAID-related bleeding is
      being debated, they should both be eliminated given their relative contribution
      to the causation of peptic ulcer hemorrhage. The search for reliable and accurate
      tools to predict outcomes after NVUGIB continues. Recent important contributions
      in this area of research are the use of a clinical prediction guide to identify
      patients who are likely to require endoscopic intervention, and the use of
      Doppler ultrasound examination of the ulcer base to predict rebleeding. The role
      of antisecretory therapy in the setting of acute NVUGIB has been revisited in two
      meta-analyses and one randomized, placebo-controlled trial of omeprazole as an
      adjunct to endoscopic intervention. Until more definitive data are available, it
      appears that the effect of acid-decreasing medications is more important when
      endoscopic therapy is not provided than when effective endoscopic intervention is
      instituted. With regard to therapeutic endoscopy for upper gastrointestinal
      bleeding, the few randomized trials that have been published in full form in the
      last year focus on the use of mechanical methods of hemostasis for peptic ulcer
      bleeding and other etiologies such as Mallory-Weiss tears and Dieulafoy lesions.

PMID- 11822007
TI  - Variceal bleeding and portal hypertension: much to learn, much to explore.
AB  - The newer diagnostic and therapeutic options continue to evolve and important
      developments have been made in the field of variceal bleeding and portal
      hypertension. A meeting was held at Baveno to update consensus on different
      terminologies in relation to portal hypertension. beta-blockers continue to be
      the mainstay for primary prophylaxis of variceal bleeding, and endoscopic
      variceal ligation (EVL) is fast emerging as a strong contender. The role of
      vasoactive drugs in the management of variceal bleeding was assessed. Octreotide
      and terlipressin were shown to be as effective as sclerotherapy in achieving
      initial hemostasis, and octreotide was shown to be safe and efficacious in the
      prevention of rebleeding. EVL was superior to endoscopic sclerotherapy (EST) for
      obliteration of esophageal varices. Sequential and simultaneous ligation and
      sclerotherapy were more effective than ligation alone, in reducing the recurrence
      rate after variceal obliteration. For gastric varices, cyanoacrylate glue
      continues to be the first line of treatment, and band ligation is being assessed
      further. Bleeding ectopic varices were dealt by appropriate endoscopic means.
      Endosonography has developed strongly in the assessment of variceal eradication
      and prediction of variceal recurrence. Transjugular intrahepatic portosystemic
      shunting (TIPS) significantly reduces rebleeding rates compared to EVL.

PMID- 11822008
TI  - Diagnosis of esophagogastric tumors.
AB  - There is increasing concern regarding the need to establish guidelines for upper
      gastrointestinal endoscopy. This applies to the reliability of the diagnosis of
      early cancer, tolerance, and the need to reduce the use of conscious sedation in
      order to contain costs--one reason why nasogastroscopy with a thin fiberscope is
      being applied with increasing success. Recent advances that have been made in the
      early diagnosis of esophageal and gastric tumors now require high-resolution
      video gastroscopes and the routine use of chromoscopy. For a long time, the
      helpful contribution made by the zoom video endoscope to the identification of
      the pit pattern in neoplastic lesions was limited to the colon. However, the most
      recent zoom endoscopes, with improved mechanical characteristics and a standard
      diameter, have now opened up relevant applications in the analysis of early
      esophageal or gastric malignancies. The best example of this is the
      identification of the pit pattern in intestinal metaplasia in Barrett's
      esophagus, although the classification of the pit pattern in upper
      gastrointestinal neoplasia is still being investigated. Spectroscopic analysis of
      the response of neoplastic tissue to an applied photon beam has been hampered by
      the complex origins of the efferent photons. Recent technology, available only
      through a physical laboratory allows simultaneous analysis of fluorescence,
      reflectance, and light scattering. In this situation, the method has obtained
      sensitivity and specificity rates of nearly 100% in classifying low-grade
      dysplasia, high-grade dysplasia, and cancer in Barrett's esophagus. With regard
      to depth exploration in the wall of the digestive tract, endosonographic
      examination using a high-frequency probe (20-30 MHz) may be challenged in the
      future by the technique of optical coherence tomography, a method that does not
      require acoustic transmission through water and provides a much higher
      resolution, of up to 10 microm. Optical coherence tomography could be used in the
      staging of intramucosal esophageal cancer and for detecting intestinal metaplasia
      in the esophagus. In conclusion, the increasing progress being made in the
      accuracy of endoscopic diagnosis emphasizes the need for cost-benefit analyses of
      screening and surveillance protocols.

PMID- 11822009
TI  - Treatment of oesophago-gastric tumours.
AB  - The incidence of oesophageal adenocarcinoma continues to rise rapidly in the West
      whereas cancer of the stomach is becoming less common. Most patients present with
      advanced disease that is not amenable to curative treatment. This review focuses
      on recent evidence on the endoscopic therapy of oesophago-gastric cancer.
      Although there are many treatment modalities available, there is a paucity of
      good quality randomised trial evidence on which to base palliative treatment
      decisions. Furthermore, although palliation of dysphagia may be improved by
      expandable metal stents or ablative therapy, there is no evidence that this
      improves survival and each of these therapies has a high frequency of
      complications particularly in longterm survivors. Exciting developments have
      however been reported in the therapy of early stage oesophago-gastric cancer.
      Endoscopic mucosal resection is particularly promising with high rates of
      complete removal of early cancer or high grade dysplasia. Long-term follow up of
      these patients is required because of high rates of metachronous tumour formation
      and at present there are no randomised trial data comparing endoscopic mucosal
      resection with conventional surgery.

PMID- 11822010
TI  - Diagnostic laparoscopy: an update.
AB  - Diagnostic laparoscopy has been in use since the last century. Advances in
      technology, coupled with increasing evidence of enhanced outcomes following its
      use, have renewed interest in this modality. Diagnostic laparoscopy guides
      surgeons in preventing unnecessary laparotomies in settings of acute abdomen,
      oncologists for accurate staging of malignancies from the esophagus to the colon,
      and hepatologists in the evaluation of acute as well as chronic liver diseases.
      Prospective clinical studies are awaited that will allow experimental
      technological advances, refining the methods of diagnostic laparoscopy, to be
      translated into more widespread use.

PMID- 11822011
TI  - Minimally invasive surgery.
AB  - During the last 10 years, minimally invasive surgery has influenced the
      techniques used in every specialty of surgical medicine. This development has not
      only led to the replacement of conventional procedures with minimally invasive
      ones, but has also stimulated surgeons to reevaluate conventional approaches with
      regard to perioperative parameters such as pain medication. However, two major
      drawbacks have emerged with the introduction of this new technique: firstly, the
      prolonged learning curve for most surgeons, in comparison with the learning
      process in open surgery; and secondly, increased costs due to investment in the
      equipment required and the use of disposable instruments, as well as longer
      operating times. In the various health-care systems around the world, these
      increased costs are not always compensated for by shorter hospital stays. This
      review focuses on major areas of indication for minimally invasive surgery in the
      gastrointestinal tract. These include functional disorders of the upper and lower
      gastrointestinal tract, obesity surgery, minimally invasive techniques in gastric
      and hepatobiliary surgery and in other solid organs, and laparoscopic colorectal
      surgery. The shortening of the hospitalization period has led to increasing use
      of outpatient laparoscopic surgery, and many centers specializing in day-care
      surgery are using these techniques. The frontiers are being pushed even further,
      as the size of the instruments is reduced to achieve better cosmetic results.
      Clinical research has also focused on the topic of expanding the indications for
      minimally invasive approaches in the elderly and in high-risk patients, to take
      advantage of the shorter hospital stays and reduced surgical trauma that are
      possible. A considerable amount of basic research has been carried out on the
      stress response during and after minimally invasive procedures, and an improved
      immune response with the minimally invasive approach has been observed, leading
      to better results after extensive oncological procedures. Robotic surgery and
      telesurgery involve new computer-aided methods that allow greater precision in
      surgical technique, as well as offering an opportunity to supply surgical skill
      and expertise remotely, over long distances. Minimally invasive surgical
      techniques are thus now fully established in routine use, and the indications are
      continuing to expand.

PMID- 11822012
TI  - A case of Castleman's disease with "downhill" varices in the absence of superior
      vena cava obstruction.
AB  - Downhill esophageal varices", classically defined as those that develop in the
      upper region of the esophagus, are less common than the "uphill" type, which is
      usually produced by portal hypertension. Various causes of downhill varices have
      been reported, but mediastinal tumor is the most common responsible lesion.
      Castleman's disease, or angiofollicular lymph node hyperplasia, is a rare
      pathological process of unknown etiology that usually develops in the
      mediastinum. We report the case of a 60-year-old woman whose large esophageal
      varices were detected incidentally. The cause was a mediastinal mass which was
      diagnosed as Castleman's disease on histopathological examination of a surgical
      specimen. This patient's varices most likely formed as a result of copious blood
      drainage from the tumor into the esophageal veins. Evidence for this was the lack
      of the classic downhill pattern, the absence of superior vena cava obstruction,
      and the fact that the varices resolved after the tumor was removed. It is our
      opinion that this type of varices should be renamed, and we suggest that
      "overflow varices" would be an appropriate term.

PMID- 11822013
TI  - The macroscopic classification of early neoplasia of the digestive tract.

PMID- 11822014
TI  - Guidelines of the French Society of Digestive Endoscopy: biliary stenting.

PMID- 11822015
TI  - Should specialist endoscopists perform all complicated endoscopies?

PMID- 11822017
TI  - Novel "through-the-endoscope" technique for removing biliary stones trapped in a
      retrieval basket.

PMID- 11822018
TI  - Portal hypertensive gastropathy: treatment with corticosteroids.

PMID- 11822019
TI  - A promising new device for use in polypectomy.

PMID- 11822020
TI  - Massive gastrointestinal hemorrhage in a renal transplant recipient due to
      visceral Kaposi's sarcoma.

PMID- 11822021
TI  - Conversion of endoscopic nasobiliary drainage to internal drainage by means of
      endoscopic scissor forceps.

PMID- 11822023
TI  - Evidence of genetic interaction between the beta-globin complex and chromosome 8q
      in the expression of fetal hemoglobin.
AB  - During human development, the switch from fetal to adult hemoglobin (Hb) is not
      complete with the residual gamma-globin expression being restricted to a subset
      of erythrocytes termed "F cells" (FC). Statistical analyses have shown the FC
      trait to be influenced by a common sequence variant (C-->T) at position -158
      upstream of the Ggamma-globin gene, termed the "XmnI-Ggamma polymorphism." The
      XmnI-Ggamma site is believed to be involved in the expression of the Ggamma
      globin gene through interaction with transcription factors, and polymorphisms in
      the transcription factors could be influencing fetal Hb expression, conditional
      on the XmnI-Ggamma site. Using a two-locus model, in which the second locus was
      the known quantitative-trait locus (QTL) at the XmnI-Ggamma site, we showed
      suggestive linkage to chromosome 8q. A maximum single-point LOD score of 4.33 and
      a multipoint LOD score of 4.75 were found in a 15-20 cM region of chromosome 8q.
      A single-locus analysis failed to show linkage of FC to the region when the XmnI
      Ggamma site was accounted for by removing its effects from the data or including
      it as a covariate. Results of the single-locus analysis were significant when the
      effects of the XmnI-Ggamma site were not accounted for in any way. The results of
      analysis in a large Indian kindred indicate that there is an interaction between
      the XmnI-Ggamma site and a QTL on chromosome 8q that is influencing the
      production of fetal Hb.

PMID- 11822025
TI  - A locus for bilateral perisylvian polymicrogyria maps to Xq28.
AB  - Polymicrogyria (PMG) is one of a large group of human cortical malformations that
      collectively account for a significant percentage of patients with epilepsy,
      congenital neurological deficits, and intellectual disability. PMG is
      characterized by an excess of small gyri and abnormal cortical lamination. The
      most common distribution is bilateral, symmetrical, and maximal, in the region
      surrounding the sylvian fissures, and is known as "bilateral perisylvian
      polymicrogyria" (BPP). Most cases are sporadic, although several families have
      been observed with multiple affected members, usually following an X-linked
      inheritance pattern. Here we report the first genetic locus for BPP mapped by
      linkage analysis in five families. Linkage places the critical region for BPP at
      Xq28 (LOD score 3.08 in Xq28, distal to DXS8103 by multipoint analysis). We
      suggest that this region contains a gene that is necessary for correct neuronal
      organization and that the identification of this gene will both enhance our
      understanding of normal cortical development and accelerate the identification of
      other genes responsible for PMG.

PMID- 11822024
TI  - Limb-girdle muscular dystrophy type 2H associated with mutation in TRIM32, a
      putative E3-ubiquitin-ligase gene.
AB  - Limb-girdle muscular dystrophy type 2H (LGMD2H) is a mild autosomal recessive
      myopathy that was first described in the Manitoba Hutterite population. Previous
      studies in our laboratory mapped the causative gene for this disease to a 6.5-Mb
      region in chromosomal region 9q31-33, flanked by D9S302 and D9S1850. We have now
      used additional families and a panel of 26 microsatellite markers to construct
      haplotypes. Twelve recombination events that reduced the size of the candidate
      region to 560 kb were identified or inferred. This region is flanked by D9S1126
      and D9S737 and contains at least four genes. Exons of these genes were sequenced
      in one affected individual, and four sequence variations were identified. The
      families included in our study and 100 control individuals were tested for these
      variations. On the basis of our results, the mutation in the tripartite-motif
      containing gene (TRIM32) that replaces aspartate with asparagine at position 487
      appears to be the causative mutation of LGMD2H. All affected individuals were
      found to be homozygous for D487N, and this mutation was not found in any of the
      controls. This mutation occurs in an NHL (named after the proteins NCL1, HT2A,
      and LIN-41) domain at a position that is highly conserved. NHL domains are known
      to be involved in protein-protein interactions. Although the function of TRIM32
      is unknown, current knowledge of the domain structure of this protein suggests
      that it may be an E3-ubiquitin ligase. If proven, this represents a new
      pathogenic mechanism leading to muscular dystrophy.

PMID- 11822027
TI  - [Effects of ionising radiation on tissues].
AB  - Radiation effects are divided into four groups: a. acute somatic, b. late
      somatic, c. genetic and d. teratogenic effects. Rapidly proliferating non
      differentiated cells are the most radiosensitive. Well known representatives of
      this class of cells are the stem cells of the hematopoietic tissues and the cells
      of the intestinal crypts. The differentiated fixed postmitotic cells are the most
      radioresistant. This class includes the long-lived neurons, skeletal muscle cells
      and erythrocytes. Carcinogenesis is the most important late effect of ionizing
      radiation. For low dose rate radiation cancer risk after 1 mSv is estimated to be
      about 5 extra death cases per 100.000.

PMID- 11822028
TI  - [Dose distribution in tissues].
AB  - Biological effects of ionising radiation are dependent on the distribution of
      doses in tissue. In this article parameters influencing the distribution of dose
      in tissue are discussed with emphasis on intraoral and rotational panoramic
      radiography. For both examinations the probability to develop stochastic effects
      is estimated. For intraoral radiography the probability ranges from 0.1 to 0.3
      per million exposures and for rotational panoramic radiography from 0.4 to 0.8
      per million. For the whole Dutch population the probability to develop stochastic
      effects is 0-2 persons per year and 0-1 person per year respectively. Dental
      radiography is therefore justified if further diagnostic information is to be
      expected and exposure circumstances are optimal.

PMID- 11822026
TI  - Individual-specific liability groups in genetic linkage, with applications to
      kindreds with Li-Fraumeni syndrome.
AB  - In this report, we present a simple and powerful way to incorporate individual
      specific liability classes into linkage analysis. The proposed method is
      applicable to both quantitative and qualitative traits. In linkage studies, we
      may have information about different covariates. Incorporation of these
      covariates along with the estimates of residual familial effects, age-at-onset
      effects, and susceptibility in the definition of liability classes can increase
      the power to detect genetic linkage. In this study, we show how one can form
      individual-specific liability classes and use these classes in standard linkage
      analysis programs, such as the widely used LINKAGE package, to perform more
      powerful genetic linkage analysis. Our simulation study shows that this approach
      yields higher LOD scores and more-accurate estimates of the recombination
      fraction in the families showing linkage. The proposed method is also applied to
      kindreds collected, at the M. D. Anderson Cancer Center, through probands with
      childhood soft-tissue sarcoma. Confirmed germ-line mutations in the p53 tumor
      suppressor gene have been identified in these families. Application of our method
      to these families yielded significantly higher LOD scores and more-accurate
      recombination fractions than did analysis that did not account for individual
      specific covariate information.

PMID- 11822029
TI  - [Projection techniques in dental radiology].
AB  - The radiographic technique largely determines the amount of information that can
      be obtained from a (dental) radiograph. Therefore an adequate choice of the
      projection technique is at least as important for dose reduction as the various
      measures for radiation protection that can be applied during the exposure.

PMID- 11822030
TI  - [Radiographic diagnosis of aberrations in the teeth and tissue in the area].
AB  - Radiographic examination of the dentition and supporting bone is pre-eminently
      the area of expertise of the dentist. The radiographic images made with the use
      of a modern dental X-ray machine and high resolution dental X-rays are highly
      detailed and give very useful and reliable information, not only of the dentition
      but also of bone and its diseases in general. In this publication several
      examples are given of the practice of oral radiologic interpretation.

PMID- 11822031
TI  - [Radiology of the temporomandibular joint. Diagnostic imaging of the
      temporomandibular joint].
AB  - Diagnostic imaging plays an important role in the diagnosis of disorders of the
      masticatory system. The most frequent disorders are osteoarthrosis and internal
      derangements. The clinical diagnosis of these disorders may be confirmed by
      diagnostic imaging. In addition, diagnostic imaging contributes to the staging of
      the degenerative changes. Techniques for examination of the temporomandibular
      joint, including conventional (panoramic, transpharyngeal, transcranial) as well
      as more sophisticated techniques (tomography, fluoroscopy, arthrography, computed
      tomography, scintigraphy and magnetic resonance imaging) are briefly described.
      The interpretation of the radiological image of the joint in health and when
      affected by osteoarthrosis and internal derangement is presented.

PMID- 11822032
TI  - [Magnetic resonance imaging. Principles and applications in the head and neck
      area].
AB  - Magnetic Resonance Imaging is one of the most recently developed imaging
      techniques of the human body. In this review the physical principles and
      applications for oral surgeons are discussed.

PMID- 11822033
TI  - [Digital image processing in dental radiology].
AB  - Advanced technological progress facilitates the feasibility of computer aided
      radiodiagnosis in dental practice. It is possible to obtain more information from
      radiography without increasing the radiation dose. Radiographic images will no
      longer be made on conventional films, but are recorded digitally by means of an
      electronic receptor. Many applications of this technology regarding archiving,
      interpretation, reconstruction, and transmission of radiographic images already
      have been demonstrated in the laboratory environment. The required software is
      expected to be available for the general practitioner in the near future.

PMID- 11822034
TI  - [Developments in the general dental practice].

PMID- 11822035
TI  - [Developments in special dentistry].

PMID- 11822036
TI  - [Watch out! Education is more and more necessary].

PMID- 11822037
TI  - [Developments in dental insurance].

PMID- 11822038
TI  - [Developments in dental research].

PMID- 11822039
TI  - [The impact factor of dentistry journals].

PMID- 11822041
TI  - [The future of specialization in dentomaxillary orthodontics].

PMID- 11822040
TI  - [Oral health in the 21st century. Future expectations based on the changes in
      dental caries prevalence in the 20th century].

PMID- 11822042
TI  - [Dentistry research in Europe].

PMID- 11822043
TI  - [Standards for craniofacial growth and development in children].

PMID- 11822045
TI  - [Dysfunction in the mandibular movement apparatus. A future perspective].

PMID- 11822044
TI  - [Dental caries: changes in therapy].

PMID- 11822046
TI  - [The end of X rays. And now what...?].

PMID- 11822047
TI  - [The future of the past. The Dutch Dentistry Museum].

PMID- 11822048
TI  - [Dental caries diagnosis with low prevalence. How big is the chance of a correct
      diagnosis?].

PMID- 11822049
TI  - [Oral medicine].

PMID- 11822050
TI  - [Development of implantations].

PMID- 11822051
TI  - [Anatomy of the urethral sphincteric vesico-prostatic complex].
AB  - As 27 different names have been proposed for the components of the urethral
      sphincter, it is difficult to build a clear anatomical model of it. Starting from
      a review of the literature and from some personal observations of surgical
      anatomy, our aim is to draw a vision as much organic as possible of the anatomy
      of the urethral sphincter. The components of the urethral sphincter are: the
      bladder neck (preprostatic sphincter), the smooth muscle urethral sphincter, the
      rhabdosphincter and levator ani muscle. Recently the rhabdosphincter has been
      proposed as a vertical structure that extends from the pelvic cavity (bladder
      base) to the perineal cavity. It can be round-shaped or omega-shaped. The
      anterior insertions are along the anterolateral aspect of the prostate
      (superiorly) and on the perineal fascia (inferiorly). The posterior insertions
      are on the Denonvilliers fascia and posterior aspect of the prostatic apex
      (superiorly) and on the central perineal tendon (inferiorly). The rhabdosphincter
      has strong means of fixations: anteriorly it is fixed to the pubis by the pubo
      urethral ligaments, posteriorly it is supported by the medial fibrous raphe of
      the perineum. The anteromedial fibres of levator ani muscle are involved in the
      continence mechanism by their strong relation with the rhabdosphincter and the
      prostate.

PMID- 11822052
TI  - [Physiology of the urethral sphincteric vesico-prostatic complex].
AB  - We propose a review of the literature about innervation and physiology of the
      urethral sphincteric complex. Parasympathetic innervation of the pelvic viscera
      comes from ventral branches of the sacral nerves (S2-S4). The orthosympathetic
      component derives from superior hypogastric plexus and runs down the hypogastric
      nerves to form the right and left pelvic plexus together with the parasympathetic
      component. The pelvic plexus is situated inferolaterally with respect to the
      rectum and runs on the surface of the levator ani muscle down to the prostatic
      apex. The pelvic plexus gives innervation to the rectum, the bladder, the
      prostate and the urethral sphincteric complex. The pelvic muscular floor is
      innervated by the somatic component (pudendal nerve) derived from the sacral
      branches (S2-S4). Bladder neck and smooth muscle urethral sphincter innervation
      is given mostly by the orthosympathetic component. The rhabdosphincter
      innervation comes from the pudendal nerve and from the pelvic plexus; its role in
      the continence mechanism is probably to give steady tonic urethral compression.
      Levator ani muscle takes part in the sphincteric complex with its anteromedial
      pubococcygeal portion. It plays its role strengthening the sphincteric tone
      during increase of the abdominal pressure or during active quick stop cessation
      of the urinary stream.

PMID- 11822054
TI  - [Personal research: reconstruction of the urethral striated sphincter].
AB  - OBJECTIVE: Incontinence is one of the drawbacks of radical prostatectomy. The
      causes of post-operative incontinence are sphincter deficiency (SD) and bladder
      dysfunction (BD). SD seems to be the main cause of incontinence and long time to
      continence. We present a surgical modification of the anatomical radical
      retropubic prostatectomy consisting in the reconstruction of the posterior aspect
      of the striated urethral sphincter in order to obtain a quick recovery of
      continence postoperatively. MATERIALS AND METHODS: Caudal retraction of the
      urethro-sphincteric complex after apical dissection of the prostate often occurs.
      Furthermore posterior fibrous raphe interruption can cause shortening of
      anatomical and functional urethral length and affect continence. In order to
      avoid caudal retraction of the sphincteric complex, after completing vesico
      urethral anastomosis, the posterior emicircumference of the striated sphincter is
      fixed to the posterior aspect of the bladder one centimeter cranially and
      posteriorly to the urethro-vesical anastomosis. The rabdosphincter is sutured
      separately from the urethro-vesical suturing. This technical modification makes
      it possible to obtain an anatomical length of the urethra of about a centimeter
      more than with the standard technique, replacing it in a more anatomical
      position. Furthermore, this technique provides the new posterior platform for the
      urethro-sphincteric complex. Twenty-four patients with clinical organ confined
      disease and age range 54-74 years (mean 64 years) underwent Walsh's anatomical
      radical retropubic prostatectomy with reconstruction of the rabdosphincter (group
      A). Catheter was removed 7 to 11 days postoperatively. Early continence was
      assessed objectively with the number of pads per day as follows: 0-1 mini pad =
      continent; 1-2 pads per day = mild incontinence; 2 or more pads per day = severe
      incontinence. Continence was evaluated at 3 days and one month after catheter
      removal. Group A compared to 21 patients (group B) who underwent standard
      anatomical RPP (historical control group). RESULTS: In group A 16/24 patients
      (66.7%) and 19/24 patients (79.2%) were continent respectively at three days
      after removal of the catheter and after one month; mild incontinence (1-2
      pads/day) was present in 6/24 patients (25%) and 3/24 (12.5%) respectively, 2/24
      patients (8.3%) suffered from severe incontinence after 3 days and one month. In
      group B 7/21 patients (33%) were continent at hospital discharge, 11/21 (52%)
      after one month. CONCLUSIONS: Careful reconstruction of the posterior aspects of
      the rabdosphincter shortens time to continence after RRP.

PMID- 11822053
TI  - [Epidemiology and physiopathology of urinary incontinence after radical
      prostatectomy].
AB  - Beginning in the 1980s, a series of anatomical discoveries were introduced to
      modify the classic retropubic radical prostatectomy proposed by Millin in 1942 in
      an effort to reduce intra and postoperative complications such as intraoperative
      bleeding and postoperative erectile dysfunction and incontinence. Urinary
      incontinence post retropubic "anatomical" radical prostatectomy remains a
      distressing problem for the patient and the physician rating from 6 to 20% even
      in the hands of experienced surgeons from high volume Academic Centers. The
      reason for the discrepancy in results is unclear and should be searched in
      surgical experience of the surgeon, volume of surgical activity of the Center,
      and selection of the patients undergoing the radical retropubic procedure. In the
      Literature we identified methodological factors which can bias the data on post
      radical retropubic prostatectomy such as 1) Consensus is lacking on definition of
      continence and/or incontinence following radical retropubic prostatectomy 2)
      Different surgical techniques are compared: sphincter damaging, versus repairing,
      versus preserving; bladder neck sparing versus non sparing; nerve sparing versus
      non sparing 3) Patients with preoperative urinary incontinence are included in
      the series and the preoperative continence status is not known. 4) Different
      timing in registration of incontinence. 5) Different methods in data collection.
      This latter seems to be the most important reason for discrepancy in the
      collection of the data. Self administered questionnaires oriented to evaluate
      incontinence analyzed by a third party seem to be the most powerful and objective
      tool for post prostatectomy incontinence rating. Post prostatectomy incontinence
      may be attributed to sphincter dysfunction as a result of surgical injury during
      prostatic surgery and/or to bladder dysfunction including detrusor instability
      and decreased compliance resulting in stress or urge or mixed stress/urge
      postoperative incontinence. In the Literature bladder dysfunction is considered
      to be responsible or jointly responsible for post RRP incontinence in a rate as
      high as 93%. More recently, a major role is considered to be played in post RRP
      incontinence pathophysiology by intrinsic sphincter insufficiency. Rarely bladder
      dysfunction is an isolated cause of incontinence. Moreover the symptom of stress
      incontinence accurately predicts the finding of intrinsic sphincter deficiency.
      The apical dissection and the preservation of the intrinsic sphincter remain the
      most complex parts of RRP and the keys to the maintenance of postoperative
      urinary continence.

PMID- 11822055
TI  - [Technical problems in achieving continence after perineal prostatectomy].
AB  - After radical perineal prostatectomy a 88% and 94% continence rate can be
      achieved respectively at 6 month and 12 month follow-up. Stress incontinence
      persists in 4.5% of cases, while in only 1.5% complete incontinence is observed
      during night and day without spontaneous voidings. In our experience of 176
      consecutive perineal radical prostatectomies we observed that in order to obtain
      a complete recovery of urinary continence, in absence of signs of detrusor
      instability, a functional urethral length more than 16 mm and urethral closure
      pressure more than 42 cm H2O are needed.

PMID- 11822056
TI  - [Technical problems in achieving continence after radical retropubic
      prostatectomy by the "digitoclasia" technique].
AB  - Radical prostatectomy today has become a frequent operation in all urology wards.
      An increasing attention is nowadays paid to the question of post-operation
      continence, which is considered a fundamental aspect for a good quality of life.
      The Authors propose two variations to the Walsh's technique: conservation of the
      distal sphincter obtained by "digitoclasic" isolation of the same and
      conservation of the proximal sphincter obtained by means of a personal
      preparation technique of the vesical neck and anastomosis of the same to the
      urethral stump. The record of cases, not large enough, and in particular some
      initial failures occurred during the finalization phase of the technique, do not
      yet allow to draw final conclusions.

PMID- 11822057
TI  - [Physiotherapy of pelvic floor for incontinence].
AB  - The rate of urinary incontinence after prostatectomy, as reported in several
      studies, varies between 0 and 88%. In the last years, pelvic floor rehabilitation
      in the women stress incontinence has been strengthened, with a great amount of
      clinical studies and results. Recently, the rehabilitation treatment has been
      studied in men who underwent a radical prostatectomy. The Cochrane Database of
      Systematic Reviews recently published the "Conservative management for post
      prostatectomy incontinence". The aim of this study was to determine the effects
      of conservative management in post prostatectomy urinary incontinence. Randomized
      or almost-randomized trials were analyzed up to January 1999; five studies were
      included, with the following results: 1. Pelvic floor muscle training versus no
      active treatment. Two trials compared pelvic floor muscle training with patients
      in a control group. In both groups there was a clinical improvement, especially
      in the first months after prostatectomy. The results of the two studies suggest a
      benefit in the treated group, even if not statistically significant, mainly in
      the first months after surgery. 2. Pelvic floor muscle training + biofeedback
      versus no active treatment. The treated group regained continence in shorter
      time, with decrease of incontinence episodes, of urinary frequency, of the
      quantity of urine loss; these data were not statistically significant. 3. Pelvic
      floor muscle training + rectal electrical stimulation versus no active treatment
      No detectable differences among the two groups, either in number of men still
      incontinent, and in Pad-test results. 4. Pelvic floor muscle training + rectal
      electrical stimulation + biofeedback versus no active treatment. Pad-test
      evaluation was similar in the treated and in the control group; no other outcomes
      were described. 5. Pelvic floor muscle training + rectal electrical stimulation
      versus pelvic floor muscle training. There was a progressive improvement in three
      months of rehabilitation, even if not statistically significant. All the studies
      showed improvement of urinary incontinence in men, independent of their trial
      allocation (treatment or control group). After an initial period of rapid
      improvement, continence improves even after the first three months, so that only
      15-20% was still incontinent by six to twelve months. IN CONCLUSION: in the post
      operative period, a supportive and educative approach is recommended to reduce
      the duration and the degree of urinary incontinence. Spontaneous recovering
      occurs particularly in the first three months: it is maintainable a delayed
      rehabilitation management, with intensive rehabilitation treatment for men with
      persistent urinary incontinence. Rehabilitation seems to be more effective in the
      first four months after surgery. Even the AHCPR Guideline recommends a
      behavioural, rehabilitative and pharmacological treatment. Research must be
      improved. Limits of the studies are: small sample sizes, incomplete randomisation
      -necessary to avoid sample "contamination"--, definition of the best timing for
      treatment; trials could be restricted to men with persistent urinary
      incontinence, or could compare early treatment with delayed more selective
      treatment. This management is intensive and resource-dependent; it may be
      difficult to justify it, unless it proves evidently effective. In our clinical
      therapeutical experience, patients undergo a physiatrist examination within 10
      days after catheter removal. The clinical examination includes: full history,
      self-evaluation questionnaire, strength (PC test: 0-5 by digital anal control),
      perianal sensibility, anal sphincter tone, presence of muscle synergies. The
      rehabilitation team immediately enrolls the patient, with an educative
      behavioural and rehabilitative approach: men are asked to fill a voiding diary,
      and have a bladder training and a first pelvic floor muscle training, with
      written instructions. Patients must know and share the therapeutical project. A
      second clinical evaluation occurs after three months: if urinary incontinence
      persists, the patient is submitted to complete rehabilitation: *Urinary
      incontinence + absence of muscle contraction (PC = 0/1): pelvic floor muscle
      training and rectal electrical stimulation; *Urinary incontinence with PC test >
      1: pelvic floor muscle training and even biofeedback (for those with poor self
      muscle consciousness). Frequency of treatment: 2-3 times a week. The aim of the
      treatment is to enable consciousness of pelvic muscles and to strengthen perineal
      function.

PMID- 11822058
TI  - [Recovery of urinary incontinence after retropubic radical prostatectomy. Results
      in 100 patients].
AB  - AIM OF THE STUDY: To shorten the time to recovery of full urinary continence
      after radical retropubic prostatectomy and to increase the postoperative
      continence rate. MATERIALS AND METHODS: One hundred and five consecutive patients
      were submitted to radical retropubic prostatectomy for prostate cancer, with
      curative intent, focusing our attention on three steps of the operation. First,
      to achieve a complete control of bleeding from the dorsal vein complex and to
      perform a minimal touch dissection of the urethral stump; second, to perform a
      conservative dissection of the bladder neck, and, third, to implement a vascular
      type, watertight, vesico urethral anastomosis. Continence was assessed 24 hours
      after catheter removal and at monthly follow up visits until full recovery and
      graded as dry if no dropping was visible and the patient was able to interrupt
      the urinary stream during micturition; stress incontinence, if any dropping was
      observed during abdominal strain between micturitions; and wet, if uncontrollable
      dropping occurred, and the number of pads needed per day recorded. RESULTS: At a
      median follow-up time of 18 months, range 6 to 30, a total of 87 of 100 evaluable
      patients (87%) resulted as dry; 10 patients (10%) resulted as having a variable
      degree of stress incontinence needing one to three pads per day, and 3 patients
      (3%) resulted as wet. In 41 of the 87 dry patients (47.1%) continence was
      achieved within the first day from catheter removal, and in a median time of 4
      weeks, range 2 to 16 in the remaining 46 patients (52.9%). CONCLUSIONS: The
      results of total continence rate of the present study seem to compare to the
      recent literature except for the time to full recovery which is shorter; it is
      difficult to identify the contribution of each single surgical step.

PMID- 11822059
TI  - [Continence problems after radical prostatectomy: role of rehabilitation of the
      pelvic floor].
AB  - Continence mechanisms can be compromised after radical prostatectomy. Relatively
      low percentages of urinary incontinence are reported (2-15%). Perineal floor
      physiotherapy is considered an actual method of treatment of urinary incontinence
      in females. It is based on pelvic floor muscles exercises, biofeedback and
      functional electrical stimulation. The aim of physiotherapy is to improve pelvic
      floor muscles proprioception, to increase tone of levator ani and to favour
      automatization of these muscles in daily life. The reports in Literature on
      perineal floor physiotherapy in treating incontinence after radical prostatectomy
      are scarce. In this paper we present our experience about 9 patients with
      incontinence post radical prostatectomy (out of 74 patients operated on at our
      Institution). We obtained an improvement or a complete cure in 78% of the treated
      patients. We believed that pelvic floor physiotherapy can be considered a good
      and safe method of treatment of incontinence after radical prostatectomy, at
      least in less serious cases.

PMID- 11822060
TI  - [Continence problems after radical prostatectomy: medical treatment].
AB  - OBJECTIVE: We hypothesized that a benefit can be obtained from both urine storage
      and urethral resistance after retropubic radical prostatectomy through the
      induction of artificial erections. MATERIAL AND METHODS: From January 1993 to
      December 2000 we have submitted 127 patients to radical retropubic prostatectomy.
      According to preoperative bladder behaviour, 59 patients (46.5%) presented
      voiding disorders, 10 (7.9%) filling disorders, 4 (3.1%) mixed disorders, whereas
      54 (42.5%) were asymptomatic. The urethral catheter was removed between the 10th
      and the 12th postoperative day. Fourteen patients entered a programme of early
      sexual rehabilitation with intracavernous injection of prostaglandin E1 (ICI)
      within 7 days from catheter removal. RESULTS: After catheter removal the recovery
      of urinary continence occurred within 2.2 +/- 2.3 days. At dismissal from the
      hospital, 8 patients (6.2%) were almost totally incontinent; 2 (1.5%) were still
      incontinent after a 6-month period; 73 (57.4%) were dismissed with clinical signs
      of detrusor instability hence treated with anticholinergic drugs such oxybutynin
      or tolterodine; 3 (2.3%) resulted obstructed after surgery because of stenosis of
      the anastomosis. Almost all the patients submitted to early sexual rehabilitation
      referred an improvement of their incontinence after the first injection. The
      patients who did not begin an early sexual rehabilitation generally recovered
      from incontinence in a longer time. CONCLUSIONS: Our preliminary observations
      showed that artificial erection PGE1-induced is effective in improving or
      accelerating post radical prostatectomy incontinence recovery. The results apply
      also to patients with pre-operatory detrusor instability.

PMID- 11822061
TI  - [Urinary incontinence: frequency and diagnostic and therapeutic approach in
      general practice in Italy].
AB  - OBJECTIVE: A large observational study was conducted to assess the frequency of
      urinary incontinence (UI) and overactive bladder (OAB) and to describe the
      diagnostic and therapeutic approach in General Medical Practice in Italy.
      MATERIALS AND METHODS: Subjects eligible for the study were men aged > 50 years
      and women aged > 40 years, observed consecutively by their own General
      Practitioner (GP) for a check-up or medical prescription examination during the
      recruitment period, who agreed to participate in the study. All the subjects
      included in the study were interviewed by their GP using a common questionnaire
      that included information about their general characteristics and a specific
      medical history. The subject was also asked: "Have you had involuntary loss of
      urine during the last 3 months?"; "Do you urinate more than 8 times a day on
      average and/or Do you have to get up more than once a night?"; "Have you urgency
      problems?". If the subject answered yes to the first question or to both the
      second and third, a urinary problem was diagnosed, in particular UI if the anser
      was yes to the first and OAB if to the second and third. In these subjects the
      interview was continued in order to define the type of UI, using the diagnostic
      flow chart proposed by Wean. RESULTS: On the whole, 9613 men (average age 64.8,
      range 50-98) and 13,365 women (average age 60.3 years, range 40-98) were
      interviewed by 774 GPs. A diagnosis of urinary problems was made in 1084 men
      (11.3%) and 1507 women (11.3%). Among the men the GP was already aware of the
      condition in 603 cases (55.6%) and a new diagnosis was made in 481 cases (44.4%).
      The corresponding figures for women were 560 (37.2%) and 947 (62.8%). The
      proportion of new diagnosis out of all the subjects with micturition problems
      tended to be greater in the younger age (chi square for trend p < 0.05). The
      presence of OAB without UI was found in 3.0% [95% Confidence Interval (CI) 1.7
      3.5] of the men and 1.1% (95% CI 0.9-1.3) of the women. Over all, 8.3% (95% CI
      7.7-8.9) of the men and 10.2% (95% CI 9.6-10.8) of the women reported UI. The
      frequency of OAB and UI conditions increased with age in both men and women. On
      the whole, a urine test was requested in 71.9% of the subjects with a new
      diagnosis of UI or OAB and the frequency of haematuria was equal to 15.7% of the
      cases, without marked differences by type of diagnosis of micturition problem. A
      urine culture was done in 60.7% of the cases and was positive in 17.7%. Further
      diagnostic investigations were prescribed in the majority of cases, 76.6%. This
      was observed in particular among the men (86.2% of the cases compared to 71.7% of
      the women) but with no substantial differences between the different diagnoses of
      UI. Pharmacological treatment was suggested to 68% of the men and 44.9% of the
      women. The condition for which pharmacological treatment was less often
      prescribed was stress UI, where it was suggested in 54.5% of the men and 27.3% of
      the women. For men, alpha-lytics were the drugs most often prescribed for all
      urinary problems, regardless of the type. For women, anticholinergics were the
      most commonly advised type of drug, followed by anti-infectives.

PMID- 11822062
TI  - [Evaluation of the association between benign prostatic hyperplasia and sexual
      disorders].
AB  - OBJECTIVE: The aim of this study was to determine the incidence of sexual
      dysfunction in patients with benign prostatic hyperplasia (BPH). METHODS: During
      the last 6 months 88 patients (mean age 65 years, range 55-78) suffering from
      BPH, without other chronic disease, were studied. RESULTS: Andrological
      evaluation enabled us to find erectile dysfunction in 52% of patients,
      ejaculation problems in 41% and decrease of libido in 54%. CONCLUSION: Due to the
      great impact of these disturbances in patients' quality of life, we believe that
      clinical and therapeutic approach in BPH patients should be global, with both
      urological and andrological assessment.

PMID- 11822063
TI  - [Histopathologic risk factors in patients with non-seminomatous germ tumors of
      the testis in clinical stage 1. Retrospective study of 75 patients].
AB  - OBJECTIVES: This retrospective study was performed to evaluate histopathologic
      prognostic risk factors in 75 patients on clinical stage 1 nonseminomatous germ
      cell cancer of the testis (NSGCTT). METHODS: From September 1976 to February 2000
      we operated on 75 patients for NSGCTT on clinical stage 1 disease. Average age
      was 29.5 years (range 16-71). After orchiectomy, therapeutic options included
      retroperitoneal lymph node dissection (RLND) for 44 patients (58.6%),
      surveillance for 26 (34.6%) and neoadjuvant chemotherapy for 5 (6.6%). Testis
      primary tumor samples were assessed for studying prognostic risk factors that
      included vascular and/or lymphatic invasion (IV/IL+), percentage of embryonal
      carcinoma (%EC) and absence of yolk sac tumor (YS-). RESULTS: All patients were
      alive and disease-free. The average age follow-up was 84.5 months (range 1-254).
      Relapses occurred in 11 (14.6%) patients after an average follow-up of 9.09
      months (range 3-24). Prognostic risk factors were detected as follows: IV/IL+ in
      17 cases (22.7%), (50-80%) EC in 23 (30.6%), CE% > 80 in 23 (30.6%), YS- in 55
      (72%). In 8 (10.6%) patients there was not any prognostic risk factor. Disease
      relapse related to prognostic risk factors was detected as follows: 18.1% for
      VI/LI, 90.9% for EC% > 50 (27.2% for 50-80% EC and 63.6% for CE% > 80) and 90.9%
      for YS-. Relapsing rates between patients with EC% > 80 and 50-80% EC resulted
      statistically significant (p = 0.02, odds ratio = 12.25). Relapsing rates between
      patients on surveillance and those who underwent RLND was next to be significant
      (p = 0.05, odds ratio 3.68). CONCLUSIONS: EC% > 80 is a prognostic risk factor
      for disease relapse in patients with clinical stage 1 NSGCT who are selected in a
      high risk group requiring RPLND or neoadjuvant chemotherapy as therapeutical
      option.

PMID- 11822064
TI  - [Superficial bladder neoplasia unresponsive to endocavitary treatment: when
      should the treatment approach be changed?].
AB  - PURPOSE: The appropriate treatment of superficial bladder neoplasm is still
      debated. The urologist must weigh the risk of tumor recurrence and progression
      against the possible side effects of conservative treatment (transurethral
      resection, intravesical therapy). Furthermore it is difficult to decide exactly
      when to abandon the conservative therapy and proceed with radical cystectomy and
      urinary diversion in order to prevent the potentially lethal sequelae of invasive
      bladder cancer. There are no certain scientific data on the appropriate
      therapeutic approach of recurrences of superficial bladder cancer after
      intravesical therapy and often the urologist takes a decision based on his
      personal experience ("art rather than science"). Based on these considerations,
      our aim was to evaluate applicable criteria to predict the risks of tumor
      recurrence and progression and so decide the best treatment for each patient.
      METHODS: 148 patients with multifocal, multirecurrent or persistent superficial
      bladder cancer (stage Ta-T1-Tis, G1-3) were treated with transurethral resection
      and/or two or more administration of intravesical chemo- (Mitomycin C,
      Doxorubicin, Epirubicin, Mitoxantron) or immuno-therapy (BCG) using common
      treatment schedule. Our first end point was the disease-free survival (DFS)
      evaluated by three different criteria: 1) "dynamic" stage (stage T1 diagnosed at
      the beginning, or during the follow-up or never); 2) "dynamic" grade (G3 tumor
      diagnosed at the beginning or during the follow-up or never); 3) "number of
      positive cystoscopies at the 3-year follow-up". Data were evaluated by a
      univariate statistical analysis (log-rank test) and a multivariate ones (MPLR
      stepwise procedure and L-ratio Cox's test). RESULTS: "Dynamic" stage: patients
      who never developed a T1 stage tumor have a better DFS than patients who
      developed a T1 stage tumor and even more than patients in which T1 was diagnosed
      from the beginning (p < 0.0001). "Dynamic" grade: patients who never developed a
      G3 tumor have a better DFS than patients who developed a G3 tumor and patients in
      which G3 tumor was diagnosed from the beginning (p < 0.0017). "Number of positive
      cystoscopies at the 3-year follow-up": patients with less than 3 positive
      cystoscopies have a better prognosis than patients with 3 or more positive
      cystoscopies at the three-year follow-up (p < 0.0380). DISCUSSION: We have found
      three independent predictive prognostic factors: "dynamic" stage, "dynamic" grade
      and number of positive cystoscopies at the 3-year follow-up. The statistical
      univariate and multivariate analyses allow us to define three risk categories for
      tumor progression (> or = T2): low, moderate, high.

PMID- 11822065
TI  - [Flexible mini-ureteroscopy in diseases of the upper urinary tract: our
      experience].
AB  - OBJECTIVE: The aim of our work is to present our experience about the use of
      flexible mini-ureteroscope in the diagnosis and therapy of some upper urinary
      tract diseases. METHODS: We evaluated the data of 52 mini-ureteroscopy performed
      with 7.4 Fr instrument. The indications for ureteroscopy were: kidney stones (25
      cases, 48.1%), filling defects (12 cases, 23.1%), positive cytology (5 cases,
      9.6%), lateralising haematuria (8 casi, 15.4%), ureteropelvic junction
      obstruction (2 cases, 3.8%). RESULTS: There were no major complications during
      procedure. The stones were fragmented by 1.9 Fr electrohydraulic probe, by 200
      and 365 m Holmium: YAG laser fiber or extracted by 0-Tip 3 Fr nitinol basket. The
      found papillary neoplasms were removed by basket or grasper and coagulated by
      laser fiber or 2 Fr electrode. The angiomas were coagulated by laser or 2 Fr
      electrode. The ureteropelvic junction was incised laterally by 365 m laser fiber
      or 3 Fr Rite-Cut. We interrupted the procedure only in 2 (3.8%) cases of lower
      pole kidney stones, because of lack of access with the laser fiber or other
      instruments. CONCLUSION: Today, the flexible mini-ureteroscopy is the gold
      standard in the diagnosis of filling defects and lateralising haematurias. This
      technique can be therapeutic also for the angiomas and the low grade tumours. In
      case of kidney stones, this technique is a less invasive alternative compared to
      percutaneous nephrolithotomy in the treatment of caliceal stones resistant to SWL
      and is the only therapy for the extremely obese patients with bleeding diathesis.

PMID- 11822066
TI  - [Cystic dysplasia of the testis: report of a case and review of the literature].
AB  - Cystic dysplasia of the testis (CDT) is a rare, benign and congenital lesion
      causing scrotal mass in pediatric population that can mimic testicular cancer.
      This lesion consists of cystic dilation of the rete testis and it is frequently
      associated with renal or genitourinary tract anomalies as renal agenesis and
      multicystic dysplasia of the kidney. This frequent presentation suggests that
      testicular cystic dysplasia is associated with a defect of the metamesonephric
      system in particular with a defect in the connection between the efferent ducts
      derived from the mesonephros and the rete testis tubules derived from the
      gonadoblastoma. The role of ultrasound is of primary importance for clinical
      diagnosis and follow-up of untreated forms. The sonographic appearance of CDT
      consists of multiple cysts in the mediastinum testis. The cysts range in size
      from microscopic to several millimetres and may involve the whole testicular
      parenchyma or have a focal aspect. If the cysts are tiny, the ultrasound must be
      able to distinguish between CDT and testicular microlithiasis, a potential
      premalignant condition. Today it is possible thanks to high frequency 7.5 to 10
      mHz probes. In the past orchiectomy has been considered as the treatment of the
      choice for CDT. Today, non operative management of CDT represents an effective
      alternative option in these patients and the primary benefit of this approach is
      the preservation of endocrine function and spermiogenic activity. However, the
      natural history of untreated CDT and its effect on normal testicular tissue are
      still unknown, therefore long-term follow-up is recommended.

PMID- 11822067
TI  - [Unusual clinical presentation of bladder diverticulum: a clinical case].
AB  - The Authors report a rare case of bladder diverticulum with radiological findings
      compatible with infiltrating bladder cancer and left ureterohydronephrosis. The
      definitive diagnosis was possible only after surgical intervention with mass
      removal and histological examination that resulted compatible with bladder
      diverticulum producing an inflammatory pseudotumor of the wall.

PMID- 11822068
TI  - [Technical solution for single kidney patients with multiple ureteral neoplasms].
AB  - When ureteral length is extensively compromised, preservation of the kidney
      without recurring to external urinary diversion may be attempted by various
      techniques. The choice depends on the extension and localization of the defect.
      We report a technique solution performed in a patient with multiple ureteral
      tumors and solitary kidney. A 70-years old underwent TURB for superficial bladder
      cancer and right nephroureterectomy for upper urinary tract tumor. He was
      admitted for hematuria and renal failure which need a percutaneous nephrostomy.
      Urography and pielo-RMN showed multiple and irregular defects of proximal left
      ureter. We performed a left ureterectomy with ureteral substitution by tailored
      and retroperitonealized ileal segment with simultaneous ileal bladder
      augmentation. The six months follow-up including serum creatinine, sonography,
      urodynamic evaluation, urinary cytology, excretory urogram and pielo-RMN shows
      good results. Ureteral replacement with ileum is indicated only for extensive
      ureteral diseases in which ureteroneocystostomy or vesical Psoas hitch and/or
      Boari bladder flap are not feasible. With particular attention to surgical
      aspects as tailoring ileum (to improve propulsion of urinary bolus, limit the
      absorbing surface area and decrease mucus formation) and the use of an ileal
      segment longer than 15 cm (to prevent reflux) and with an accurate patient
      selection, we think that this procedure can assure satisfactory results also in
      difficult cases.

PMID- 11822069
TI  - [Uro-andrologic prevention of male infertility].
AB  - The Authors analyze the more frequent uro-andrological pathologies correlated
      with male infertility and consider the causes of impoverishment in semen in
      industrialized countries. They analyze preventing possibilities to maintain the
      normal physiological level of fertility in young male in various uro-andrological
      pathologies.

PMID- 11822070
TI  - Diagnosis of tuberculosis: the polymerase chain reaction (PCR).

PMID- 11822071
TI  - Current concepts in the treatment of radial head fractures in the adult. A
      clinical and biomechanical approach.
AB  - The treatment of simple radial head fractures type Mason-Hotchkiss 1 and 2 is
      unequivocal. In the case of a displacement of less than 2 mm (Mason-Hotchkiss 1),
      functional conservative treatment is indicated. If the displacement is more than
      2 mm (Mason-Hotchkiss 2) internal fixation is indicated, combined with treatment
      of the soft-tissue injuries. The treatment of comminuted radial head fractures
      Mason-Hotchkiss type 3 is more controversial, as they are usually associated with
      ligament injuries. Conservative treatment appears to have unsatisfactory results.
      Opinions differ on surgical treatment, i.e. 1) excision of the radial head; 2)
      reconstruction by means of internal fixation; 3) excision and reconstruction with
      a prosthesis. Basic experimental research on human cadaver elbows shows the
      importance of the conservation of the radial head, especially in case of
      associated soft tissue injuries. In most cases a stable osteosynthesis is
      impossible, and in case of associated ligament disruptions, resection and
      reconstruction by means of a rigid radial head prosthesis should be considered.
      Experimental research demonstrates promising results for rigid radial head
      prostheses in human cadaver elbows with a resected radial head and failing
      medical collateral ligament. Short-term clinical studies seem to confirm this,
      but long-term results are as yet unknown.

PMID- 11822072
TI  - Surgery for primary bone sarcomas of the pelvis.
AB  - Primary bone sarcomas of the pelvis represent the most challenging problem in
      limb-saving surgery. Chondrosarcoma is the most common type, followed by
      osteosarcoma and Ewing's sarcoma. The symptoms are often vague, so that the
      diagnosis is made late, when the tumor has already reached a large size. Nowadays
      hindquarter amputation is reserved for complex tumors involving the sacrum, the
      sciatic nerve, the iliac vessels or the bladder. Internal hemipelvectomy should
      be undertaken whenever possible; the reconstructive techniques are based on the
      three anatomic regions concerned: ilium, periacetabular area, and pubis.
      Complications occur in more than 50% of the patients. The 5-year survival rate is
      about 55%. Special scores, such as the MSTS/ISOLS and the TESS score, should be
      used to make the various studies comparable.

PMID- 11822073
TI  - The use of a hook-plate in the management of acromioclavicular injuries. Report
      of ten cases.
AB  - A hook-plate is a clavicular small fragment AO plate with a hook engaging below
      the acromion. It is primarily used to secure the ligament repair in the treatment
      of displaced acromioclavicular joint dislocations. We have used the hook-plate in
      conjunction with a Weaver-Dunn procedure to secure the repair in seven patients.
      In another three we used this plate to reduce and stabilize distal clavicular
      fractures. Satisfactory results were obtained in all patients; the deformity
      disappeared, full pain-free shoulder movement was regained with no motor
      weakness, with a mean follow-up of 11 months (6-25 months). Our patients returned
      early to work and sports activities (mean period of three months). The three
      clavicular fractures healed. One patient developed a superficial would infection,
      which responded to antibiotics and would dressing. None of our patients required
      removal of the implant. The hook-plate appears to be a useful device for
      acromioclavicular trauma.

PMID- 11822074
TI  - Osseous overgrowth in congenital amputations of the upper limb: report of 3 cases
      treated with autologous stump plasty.
AB  - Osseous overgrowth is an important problem after traumatic or surgical
      amputations in children. It is rather exceptional in congenital amputations. We
      report three cases of congenital amputation of the humerus with osseous
      overgrowth. They were treated with an autologous stump plasty according to
      Marquardt's technique.

PMID- 11822075
TI  - Metastatic involvement of the humerus: a retrospective study of 51 cases.
AB  - The authors performed a retrospective review of 53 patients with 56 completed or
      impending pathological fractures of the humerus. Sixteen cases were treated with
      a proximal and one with a distal humeral prosthesis, 38 with an intramedullary
      device with cement and one with plate fixation. Forty-eight patients with 51
      humeral metastases were available to follow-up. No or only occasional pain was
      observed in 92% of the operated extremities and adequate postoperative function
      in 90%. No major complications occurred, except one rod migration.

PMID- 11822076
TI  - Ulnar variance and the shape of the lunate bone. A radiological investigation.
AB  - The authors designed a study to test the hypothesis that the length of the ulna
      might affect the shape of the lunate bone because of long-term molding during
      life. This might then be useful to predict the presence or absence of a dynamic
      or static ulna plus by the shape of the lunate bone. In a prospective study,
      posterior-anterior wrist x-rays were taken in a standard fashion in 68 patients
      with a mean age of 34.5 years. Dominance, grip strength, ulnar variance and the
      shape of the lunate were recorded. Lunate shape, type 1, which is the least
      molded, was seen most frequently on both the left and right side and did not
      correlate with the dominant side. The most molded, type 3, was seen less
      frequently and almost exclusively on the nondominant side. No correlation was
      found between dynamic ulna plus and the type 3 lunate. Following statistical
      analysis, no correlation between ulnar variance and lunate shape was found,
      indicating that the shape of the lunate bone had no predictive value for
      predicting the presence or absence of a dynamic ulna plus variance. The
      hypothesis that the length of the ulna might influence the ultimate shape of the
      lunate could not be demonstrated.

PMID- 11822077
TI  - Treatment of intertrochanteric fractures by external fixation.
AB  - In this study, we aimed to evaluate the results of treatment of intertrochanteric
      fractures of the femur by external fixation in 33 patients with an average age of
      65.9 years. Patients in the study had Evans stable type 1 intertrochanteric
      fractures and unstable type 1 fractures that could be reduced to anatomical or
      nearly anatomical position by closed manipulation under fluoroscopy. The average
      follow-up period was 24 months (range, 12 to 40 months). There was no mortality
      in the early postoperative period, but the mortality within six month following
      surgery was 39%. Complete fracture healing was achieved in all patients. The
      fixator was removed after an average of 94 days (75 to 130 days) at the
      outpatient clinic. Varus malalignment of more than 20 degrees and limb shortening
      greater than 2 cm were noted in 3 patients. Pin-tract infection was seen around
      10 pins (7%). Osteomyelitis was not noted in any patients. Treatment of
      intertrochanteric fractures by external fixation is simple and can be done under
      local anesthesia together with narcotic analgesic support. It allows early
      mobilization, and implant removal is easy. Therefore we think that external
      fixation is a valuable alternative in high-risk geriatric patients.

PMID- 11822078
TI  - Kinematic and kinetic evaluation of the ankle after intramuscular injection of
      botulinum toxin A in children with cerebral palsy.
AB  - Intramuscular botulinum toxin A (BTA) injection has a role in the conservative
      management of dynamic equinus deformity in children with cerebral palsy. The
      effect of BTA injection of the gastrocsoleus muscle during gait was evaluated.
      Eight children with hemiplegia (median age 4.4 years, range 2 to 8 years) were
      included in this retrospective study. Assessment included kinematic and kinetic
      gait analysis before and after (median 57.5 days) treatment. Postinjective
      kinematics showed significant improvement of ankle range of motion in the stance
      phase of gait. Ankle kinetics demonstrated a significant decrease of pathological
      power generation in midstance. The ankle power quotient (APQ) was also
      significantly improved. Ankle power in terminal stance was improved, although not
      to a significant level. These results provide evidence of normalization of energy
      production at the ankle, which is critical for normal gait. The effect of BTA is
      temporary and can be successfully repeated. This allows deferring the need for
      surgical intervention until the child is older and recurrence rate is lower.

PMID- 11822079
TI  - [Anterior tarsectomy for cavus foot. Retrospective study of 52 cases].
AB  - The authors reviewed 34 patients treated by tarsectomy for idiopathic pes cavus
      deformity between 1977 and 1996. Fifty two feet were treated surgically. All
      patients had undergone previous conservative treatment. The average age was 40
      years. Podoscopic examination revealed 24 cavus feet stage 2, 28 cavus feet stage
      3, adduction of the forefoot in 15 cases and an equinus deformity in 8 cases. On
      radiographic examination, Djian-Annonier's angle was 108 degrees on average. All
      patients were evaluated with a minimum ot two years follow-up, according to the
      evaluation system of the Massachusetts General Hospital. With an average follow
      up of six years and six months, overall results were; 65.5% very good and good,
      21% fair, 13.5% poor. The morphological correction was poor in 9 cases. Djian
      Annonier's angle was 125 degrees on average. A number of cavus feet do not
      justify surgical treatment, because they are well tolerated, sometimes with
      orthopedic orthoses. Tarsectomy must be avoided in neurological conditions. We do
      not advise release of soft tissue or Dwyer's calcaneal osteotomy. In our opinion,
      the choice indication for anterior tarsectomy is the nonrigid cavus foot. It must
      be combined with lengthening of the Achilles tendon when a deficit of
      dorsiflexion of the foot persists following tarsectomy. According to their
      importance, associated deformations will be treated in the same operative session
      or not.

PMID- 11822080
TI  - Fluoroscopy-guided transpedicular trocar biopsy of the spine--results, review,
      and technical notes.
AB  - The purpose of this study was to evaluate the technique and value of fluoroscopy
      guided percutaneous transpedicular trocar biopsy in obtaining diagnostic tissue
      from vertebral body lesions and to review the current literature. The bone cores
      from 32 patients who underwent 34 transpedicular Jamshidi trocar biopsies for
      lesions in the thoracic, lumbar and sacral spine were examined. All samples were
      examined macroscopically for length and breakage and microscopically for
      trabeculae, marrow, and artifacts. Each sample was graded for its value for
      histologic examination. The diagnostic accuracy was assessed by the patient's
      clinical course and follow-up examinations. In 30 (93.8%) of the 32 patients a
      confirmed diagnosis or exclusion of pathology could be made. In 31 (91.2%) of 34
      biopsies the quality of the specimen was assessed as "excellent". Two (5.9%)
      specimens were "good" and one (2.9%) was "poor". There were two minor
      complications (5.9%). Transpedicular biopsy of the spine using a Jamshidi trocar
      with an internal diameter of 3.1 mm under fluoroscopic guidance can be performed
      safely and efficiently and provides suitable bone cores for histologic
      examination. A combined clinical, radiological and pathological approach to the
      lesions leads to an excellent diagnostic yield.

PMID- 11822081
TI  - [Corrective osteotomy using Hoffmann II external fixators for extra-auricular
      malunion of the distal radius].
AB  - The authors present the technique and clinical results of a corrective osteotomy
      for malunion following extra-articular fractures of the distal radius. External
      fixation allows restoration of the length of the radius with minimal damage to
      the periosteum. It allows early mobilization of the radiocarpal joint. The
      position of the distal pins provides intraoperative visual control of the angular
      correction. The minimal invasive approach decreases the risk of iatrogenic lesion
      of an extensor tendon or a sensitive branch of the radial nerve. This technique
      is easy and reliable.

PMID- 11822082
TI  - Tuberculosis of the clavicle presenting as an expansile lytic lesion: a case
      report.
AB  - An unusual case of skeletal tuberculosis, presenting as an expansile osteolytic
      lesion in the lateral end of the clavicle is presented. Diagnostic confusion
      delayed appropriate medical therapy, leading to development of a discharging
      sinus with secondary infection, which further confused the picture. With re
      emergence of tuberculosis as an important infection worldwide, and the ability of
      this disease to mimic many skeletal pathologies, this has to be included in the
      differential diagnosis, especially at unusual sites.

PMID- 11822083
TI  - Use of polymerase chain reaction in diagnosis of occult tuberculosis of the
      fibula.
AB  - An unusual case of tuberculosis of the lower end of the fibula in a young patient
      is reported. The patient presented with symptoms of pain and swelling over the
      outer aspect of the right ankle with full range of painless ankle movements. The
      plain radiographs of the ankle were normal but MRI scan showed increased signals
      within the lower end of the fibula on T2-weighted images. The histology of the
      lesion showed only a few Langhans giant cells and culture failed to grow any
      organism. Polymerase chain reaction analysis of the biopsy specimen, however,
      showed growth of Mycobacterium tuberculosis. The patient responded to
      antitubercular treatment with complete resolution of symptoms. Polymerase chain
      reaction analysis should be considered in atypical presentations with bone pain
      to rule out an occult infectious pathology.

PMID- 11822084
TI  - Textiloma of the thigh presenting as a sarcoma.
AB  - Textiloma is defined as a tumor composed of cotton matrix surrounded by
      granulomatous reaction. It occurs following operations in which surgical sponges
      were inadvertently left behind. We describe a case of a 59-year-old man
      presenting with a pathologic fracture of the proximal left femur. The results of
      the biopsy, unlike diagnoses suggested by radiographs, CT scan and magnetic
      resonance imaging revealed a textiloma of 23 years of evolution. Because of major
      bone loss, resection of the involved bone was performed followed by ipsilateral
      fibular bone graft.

PMID- 11822085
TI  - [Compound fracture of the ankle treated by locked retrograde transplantar
      nailing: a case report].
AB  - The authors describe the use of a locked retrograde plantar nailing as primary
      treatment for a severe trauma of the ankle (trimalleolar fracture associated with
      posterior dislocation and a compound talus fracture).

PMID- 11822086
TI  - [Progressive correction of an ulnar clubhand secondary to post-traumatic
      epiphysiodesis of the distal ulna].
AB  - The authors report the correction of an ulnar club-hand in a 16 year-old boy who
      complained of recurrent wrist pain after a fracture of both bones of his left
      forearm treated by internal fixation at the age of nine years. Correction was
      achieved by progressive ulnar lengthening, using Ilizarov's method, without
      radius osteotomy or bone grafting. Union was achieved 2 months post-operatively.
      Functional outcome and cosmetic appearance were satisfying.

PMID- 11822087
TI  - Association of severe autosomal recessive osteopetrosis and Dandy-Walker syndrome
      with agenesis of the corpus callosum.
AB  - A severe form of autosomal recessive osteopetrosis associated with Dandy-Walker
      syndrome and agenesis of the corpus callosum is reported in a full-term boy born
      to consanguineous parents. The diagnosis was made shortly after birth. Clinical
      features were cranio-facial dysmorphy, macrocephaly, hepatosplenomegaly, severe
      anemia and thrombocytopenia. Skeletal radiographs revealed generalized increase
      in bone density and abnormal metaphyseal remodeling. Cranial ultrasonogram and
      computed tomography scan showed Dandy-Walker syndrome, agenesis of corpus
      callosum and hydrocephalus. The patient rapidly developed severe medullary
      deficiency and a severe pulmonary infection. He died at the age of 2 months. This
      association seems extremely rare and was not previously reported in the
      literature.

PMID- 11822088
TI  - Leprosy elimination campaigns.

PMID- 11822089
TI  - Progress towards interrupting indigenous measles transmission, WHO Region of the
      Americas.

PMID- 11822090
TI  - [Anthrax].
AB  - Anthrax is a serious bacterial infection sustained by Bacillus anthracis and
      occurring in most mammals, especially grazing herbivors, but it can also involve
      humans when bacterial endospores enter the body through abrasions in the skin or
      by inhalation or ingestion. Human disease results from contact with infected
      animals or contaminated animal products, while there are no known cases of human
      to-human transmission. The most common form of human anthrax is the cutaneous
      infection, usually curable with antimicrobial therapy and rarely leading to
      systemic and fatal disease; on the other hand, gastrointestinal and inhalatory
      forms (resulting from inhalation or ingestion of endospores) are very uncommon,
      but they show a mortality rate approaching 100 percent, usually related to septic
      and toxic shock. For centuries, anthrax has caused disease in animals and only a
      few cases in humans, with some outbreaks in developing countries. Today, after
      the new events in the United States, at least 17 nations are believed to have
      offensive biological weapon programs, and this old bacterial infection became a
      modern menace to world safety.

PMID- 11822091
TI  - [Recovery of transplantable hematopoietic progenitor cells from the umbilical
      cord blood].
AB  - Cord blood (CB) is a source of transplantable hematopoietic progenitor cells
      (HPC); it represents an alternative to bone marrow to restore hematopoiesis in
      patients affected by malignant and non-malignant disease. Therefore, large-scale
      CB banks would be a natural complement to bone marrow donor registries. Storage
      of unmanipulated whole CB units requires a great number of liquid nitrogen
      containers. Separation of leukocytes allows CB storage in smaller space, thus
      lowering banking costs; unfortunately, CB processing may cause significant losses
      of stem/progenitor cells. We describe here a procedure for erythrocyte removal
      from CB units by 1 xg sedimentation on Emagel, a gelatin-based colloidal compound
      commonly used as plasma expander. The erythrocyte-depleted supernatant was
      collected and then centrifuged to recover the leukocyte pool. We evaluated
      erythrocyte depletion and leukocyte recovery after different sedimentation time
      (30, 45 and 60 min), on 139 CB units collected at delivery. All the considered
      parameters were improved by increasing sedimentation time. Erythrocyte depletion
      at 60 min was 86.0% and we recovered 93.3% of CD34+ cells. The proposed CB
      processing method allowed us to collect a satisfactory amount of HPC in view of
      stem cell transplantation; it may have a potential role in UCB banking.

PMID- 11822092
TI  - [Cardiovascular risk factors and diseases in centenarians].
AB  - Aging is considered a product of an interaction between genetic, environmental
      and lifestyle factors. Are centenarians, who have almost arrived at the maximum
      life-span (120 yrs), free of cardiovascular disease or do they have an increased
      resistance? How many cardiovascular risk factors are present? We have studied a
      group of 148 centenarians selected from registered residents of Rome (average age
      101.8 +/- 1.9; range 100-108). Their health was assessed through direct 1.5 hour
      interviews, conducted by physicians with geriatric training at the patient's
      residence, which includes geriatric assessment scales' submission. The prevalence
      of cardiovascular disease of our centenarians is 16.7%, represented by heart
      failure (8%), myocardial infarction (4.7%) and angina pectoris (4%). Among the
      cardiovascular risk factors, hypertension (31.1%) and hypercholesterolemia are
      the most frequent, while diabetes is not present. These data, compared with
      younger samples, point out a lower percentage of cardiovascular disease and risk
      factors. Moreover centenarians have always conducted a healthy lifestyle
      (Mediterranean diet, smoking abstention, physical activity, low levels of anxiety
      and depression). Finally, having identified the golden mean which allows us to
      carry out a programmed intervention for the prevention of cardiovascular risk
      factors and diseases, we will be able to increase longevity, allowing a larger
      number of subjects to reach the maximum human life-span.

PMID- 11822093
TI  - [Portal hypertensive gastropathy in patients with cirrhosis of the liver].
AB  - Portal hypertensive gastropathy (PHG) is characterized by changes in the
      endoscopic appearance of the gastric mucosa, specific for portal hypertension.
      The identification of the elementary lesions of PHG allowed the development of a
      reproducible classification, defining mild and severe pictures, and the execution
      of a natural history study. This study showed a 80% overall prevalence of PHG in
      patient with cirrhosis of the liver and a correlation between duration of the
      disease and development of PHG. PHG has often been shown to be a fluctuating
      condition, thus suggesting that its pathophysiology is not only related to portal
      hypertension, but also to other, yet unknown, factors. Bleeding from PHG did not
      occur in patients with a recent diagnosis of liver cirrhosis. Acute and chronic
      bleeding occurred in 2.5% and 12% of patients, respectively. The death rate from
      acute PHG bleeding was lower (12.5%) than the death rate of variceal bleeding
      (39.1%). Vasoactive drugs can be used in the treatment of acute PHG bleeding. For
      chronic bleeding, non selective 13-blockers and, if needed, iron, are the
      treatment of choice. TIPS or surgical portosystemic shunt may be considered for
      acute or chronic PHG bleeding, if medical treatment fails. Clinical controlled
      trials are needed to evaluate the efficacy of these or other treatments.

PMID- 11822094
TI  - [Primary Sjogren's syndrome. A longitudinal study of 68 patients].
AB  - There are only few studies, regarding primary Sjogren's syndrome (pSS) long-term
      clinical course. Moreover, it has been often studied in a restricted number of
      patients, employing different recruitment and diagnostic criteria. During a 10
      years follow-up, we longitudinally evaluate clinical course as well as severe
      complications and mortality rates in 68 patients with pSS, diagnosed according to
      the Fox's criteria. Patients were divided into 2 groups according to the
      autoantibodies pattern detected at the diagnosis: anti-Ro and/or La positive and
      anti-Ro La negative. Glandular manifestations of pSS were distinctively present
      in the majority of patients already at time of the diagnosis and serological
      findings remained typically constant during the whole follow-up. Increased IgG,
      IgA and ESR as well as low C4 serum levels were significantly prevalent in the Ro
      and/or La positive group. Finally, we did not found any significant increase in
      the mortality rate of pSS patients in comparison with the general population.

PMID- 11822095
TI  - [Genotypic sex and phenotypic sex: clinical, biochemical and molecular aspects in
      a patient with male hypogonadism and 46XX-45XO karyotype].
AB  - We report here the case of a patient with primary male ipogonadism, with small
      testes and deficient virilization of the external genitalia, but with 46XX, 45X0
      karyotype. Hormonal determinations showed high LH and FSH and low testosterone
      levels. Ultrasonography confirmed the presence of small testes within the
      scrotum. Cytogenetic analysis demonstrated a female karyotype, with 90% 46XX, 10%
      45X0 mosaicism. Using DNA probes for genes located on the Y chromosome, the
      presence of the "Sex-Determining Region" of the Y chromosome (SRY) was evidenced
      in the genomic DNA of this patient. By Fluorescence in Situ Hybridization (FISH),
      SRY locus was localized in the p terminal region of an X chromosome. SRY is the
      primary inducer of testis development; it acts as a transcription factor leading
      to a sequence of gene activations critical in the process of testicular
      differentiation and morphogenesis. A condition characterized by testicular
      development in subjects who lack a normal Y chromosome has been described; most
      of these patients are carriers of the short arm of the Y chromosome transferred
      to one of the two X chromosome, suggesting a form of X-Y paternal interchange. In
      our patient, the development of male gonade in the absence of an Y chromosome was
      explained by the demonstration of the SRY gene in an X chromosome.

PMID- 11822097
TI  - [Hemoptysis in a patient with post-obstructive pneumonia due to a broncholith].
AB  - A case of a 51-year-old man admitted to the hospital for hemoptysis after a three
      week history of fever and cough is presented. The chest x-ray film revealed
      consolidation in the left upper lobe. Because microbiologic studies of the
      bronchial lavage showed the grew of Pseudomonas aeruginosa, the patient was
      treated with piperacilline and pefloxacin. Haemoptysis and abnormal temperature
      was persistent for several days. Revaluation of the chest x-ray permitted to
      discover a little calcified nodule of 1 mm diameter. CT scan of the thorax
      confirmed the consolidation of the left upper lobe and the little calcification.
      A second fiberoptic bronchoscopy was performed in 10th day, using a bronchoscope
      with a smaller diameter; it was possible to observe the occlusion of the
      subsegment bronchus LB 1&2 due to a mobile protruding mass. The mass was gentle
      removed by the use of alligator bioptic forceps; it presented as a grey, hard, 2
      mm diameter body with irregular surface like a "floating mine". On microscopical
      examination of the mass, aspergillus hyphae appeared as broad septate filaments.
      Culture of the samples were negative. Haemoptysis and fever stopped after FOB.
      Chest x-ray in 19th day was negative: consolidation and calcification were
      absent.

PMID- 11822096
TI  - [A case of temporal arteritis presenting with sensorineural hearing loss].
AB  - The inflammatory lesions in giant cell arteritis involve the cranial branches of
      the arteries originating from the arch of the aorta most prominently. The vessels
      are thickened tender, and nodular with absent or reduced pulsation. In literature
      sensorineural hearing loss and Horton's arteritis are rarely associated. A case
      of temporal arteritis presenting with sensorineural hearing loss is described.

PMID- 11822098
TI  - [Hemoptysis from dorsal tongue base varices secondary to portal hypertension].
AB  - Portal hypertension secondary to cirrhosis of the liver is the main factor
      leading to the formation of portosystemic collaterals. The sites of such
      collateral circulation are well known. We describe a case of haemoptysis from
      dorsal tongue base varices, which are not recognised as portosystemic
      anastomosis, in a cirrhotic patient with portal hypertension.

PMID- 11822100
TI  - [The letter of discharge from hospital of a patient with liver cirrhosis].
AB  - The guidelines for the letter of discharge from hospital of patient with hepatic
      cirrhosis are summarized, underlining the relevance of providing information on
      the clinical conditions, the etiology, the morbid associations and the
      complications. The letter should also contain recommendations for an appropriate
      treatment of the patient.

PMID- 11822099
TI  - [Hepatogenic diabetes].
AB  - Peripheral insulin-resistance and impairment of the hepatocellular function are
      two major possible causes of diabetes mellitus in liver cirrhosis. The
      pathogenesis of insulin-resistance (receptorial or post-receptorial) is unknown
      but it represents an important complication because it has a profound impact on
      the pathology and natural history of the liver disease. The beta-cell capacity,
      to compensate the insulin-resistant state to avoid the onset of frank diabetes
      mellitus plays a critical importance. Many factors may induce a reduction of the
      beta-cell function in patients with liver cirrhosis: some are due to a
      predisposition to the development of diabetes: genetic or environmental,
      unrelated to the hepatic disease; some others are hepatic disease-dependent
      (excess liver and islet of Langerhans iron deposition, HCV infection rather than
      other hepatic infections, the co-presence of HCC) and may be crucial because
      additive to the previous. It is likely that the high prevalence of diabetes in
      liver cirrhosis is due to the early onset of strong insulin-resistance coupled to
      a deficient beta-cell function aggravated by hepatic disease-related factors.

PMID- 11822101
TI  - [The kinin system: biological mechanisms and clinical implications].
AB  - The discovery of the kinin system is not recent, but its study in clinical field
      has been done only in the last years. This system is composed by substrates
      (kininogens) and plasma and tissue kallikreins are the specific activators of
      these substrates producing two vasoactive peptides called bradykinin and
      kallidin. The biologic effects of kinins are mediated by specific receptors
      called B1 and B2. The activation of this system is particularly important in
      blood pressure regulation and in inflammatory reactions. The kinin system is
      involved in many clinical situations including respiratory allergic reactions,
      septic shock, hypertension and its treatment, hypotensive transfusion reactions,
      heart diseases, pancreatitis, hereditary and acquired angioedema, Alzheimer's
      disease and liver cirrhosis with ascites. The study of the kinin system in
      clinical field, which had been limited by methodological difficulties, has now
      received an important stimulus by the recent availability of specific and
      sensitive methods of dosage.

PMID- 11822102
TI  - [Is the lung a target organ in inflammatory bowel disease?].
AB  - Inflammatory bowel disease is a systemic illness that may involve the lung. The
      most common manifestation of pulmonary involvement is an asymptomatic reduction
      in lung transfer factor for carbon monoxide (Dlco) and a small airway disorders
      easy to find in subjects with active disease. Some patients show a bronchial
      inflammation and suppuration with or without bronchiectasis poorly responsive to
      antibiotics but responding dramatically to inhaled steroids. Others present a
      severe tracheal inflammation and obstruction with an inflammatory mass bulging
      into the tracheal lumen, these subjects usually respond to methylprednisolone, in
      rare cases an emergency laser ablation may be necessary. Interstitial lung
      disease and pulmonary infiltrate with eosinophilia are the most difficult
      patterns to address because in some cases drugs such as sulfasalazina and 5
      aminosalicylate may play a contributing role.

PMID- 11822103
TI  - [Losartan and the kidney protection. The RENAAL study].

PMID- 11822104
TI  - [Controversies on the treatment of atrial fibrillation].

PMID- 11822105
TI  - [Prevention of venous thromboembolism: how important is it in non-surgical
      disease?].

PMID- 11822106
TI  - [Antithrombotic treatment of acute coronary syndromes].

PMID- 11822107
TI  - [Prevention of venous thromboembolism: what still remains to be known].

PMID- 11822108
TI  - [Low-molecular weight heparin: questions asked to the physician].

PMID- 11822109
TI  - [Prevention of venous thromboembolism: controversies on the table].

PMID- 11822110
TI  - Healthy people 2010 oral health objectives--the role of AAPHD.

PMID- 11822111
TI  - Toothbrushing competency among high-risk grade one students: an evaluation of two
      methods of dental health education.
AB  - OBJECTIVE: To evaluate the effectiveness of two methods of dental health
      education (DHE) for improving toothbrushing competency among grade one students
      at high risk for dental diseases. METHODS: Fifty elementary schools in the former
      city of North York, Ontario, Canada, were assigned to one of two groups. In one
      group, students received a classroom-based DHE lesson that was reinforced by two
      small group sessions (n = 243). In the other group, students received only a
      single classroom-based DHE lesson (n = 206). Trained examiners assessed 11
      toothbrushing skills at pre- and postintervention. RESULTS: At the
      preintervention test, few significant differences were found between the groups
      and many students did not display competency in fundamental oral health skills,
      such as placing a toothbrush at the gum line. Following DHE interventions,
      students in both groups demonstrated improvements in most skills. A significantly
      higher proportion of students who received both classroom and small group
      sessions displayed gains in competency in three skills, compared to students
      receiving only a classroom lesson. These skills were brushing anterior lingual
      surfaces, brushing posterior lingual surfaces, and brushing all areas in a
      routine fashion. Students receiving only a classroom session did not display
      greater improvements in any skill areas compared to "classroom plus small group"
      students. Some students in both groups still lacked fundamental skills at the end
      of the DHE program. CONCLUSIONS: While one must exercise caution in interpreting
      the results due to several methodologic limitations, findings suggest that for
      high-risk grade one students, a classroom-based lesson combined with small group
      sessions is a more effective method of improving toothbrushing skills compared to
      a single classroom-based lesson.

PMID- 11822112
TI  - Dental caries experience, tooth loss, and factors associated with unmet needs of
      Haitian immigrants in New York City.
AB  - OBJECTIVE: The aim of this study was to characterize the dental caries
      experience, tooth loss, and unmet need of a group of Haitian immigrant residents
      of New York City. METHODS: A purposive sample of 523 adults was obtained through
      community outreach activities during 1997-98. Clinical examinations were
      performed by calibrated examiners, according to NIDCR criteria. A comprehensive
      survey also was administered to all the participants. RESULTS: For the whole
      group, the mean number of missing teeth was 2.64 (SD = 4.12), the mean DMFT =
      6.05 (SD = 5.26), the mean DMFS = 18.80 (SD = 21.04), and the mean DFS = 5.58 (SD
      = 6.17). Seventeen percent of the subjects had all their teeth sound, 59 percent
      had at least one tooth missing, 60 percent had at least one decayed tooth, and
      only 38 percent had restorations. Multivariate analyses showed that age, sex,
      education, dental insurance, frequency of dental visits, and dental floss use
      were predictors of unmet need. CONCLUSIONS: Although results showed a relatively
      low caries experience among this group of Haitian immigrants, the unmet need was
      very high. Furthermore, the tooth loss experience was relatively high for all age
      groups, further denoting a lack of access to preventive and restorative services.

PMID- 11822113
TI  - AAPHD 2001 Distinguished Service Award: Brian Burt, BDS, MPH, PhD.

PMID- 11822114
TI  - 2001 Special Merit Award: Robert J. Collins, DMD, MPH.

PMID- 11822115
TI  - 2001 Special Merit Award: Caswell A. Evans, DDS, MPH.

PMID- 11822116
TI  - 2001 Public Service Award: David Satcher, MD, PhD.

PMID- 11822117
TI  - 2001 Special Merit Award for Outstanding Achievement in Community Dentistry
      International: Dr. Fumio Yamashita.

PMID- 11822118
TI  - 2001 President's Award: James W. Toothaker, DDS, MPH.

PMID- 11822119
TI  - [Pain in the upper jaw].

PMID- 11822120
TI  - [Amalgam. I. The third amalgam war. II. Mercury sources].

PMID- 11822121
TI  - [Amalgam. III. Mercury release from amalgam restorations].
AB  - Patients are exposed to mercury during dental treatment. The major source of
      exposure to mercury is, however the release of mercury both as vapour and as
      dissolved mercury, from amalgam restorations. With regard to the dissolution in
      saliva, corrosion of the restorations appears to be of importance. The modern
      amalgams have a lower corrosion rate than older ones but emit probably more
      mercury vapour. Different measurement methods show a rather varying amount of
      mercury release. The amount of mercury in the tracheal air is of more
      significance than that in the mouth air. It has been stated that from
      restorations made of old brands of amalgam 73% of the mercury is disappeared, but
      according to our estimation utmost 2% will disappear from a large restoration of
      modern brands.

PMID- 11822122
TI  - [A dentogenic focus].

PMID- 11822124
TI  - [Palate necrosis and dermatitis after endodontic treatment].

PMID- 11822123
TI  - [Amalgam. VII. Toxic effects of mercury from amalgam fillings].
AB  - Chronic exposure to mercury may lead to damage of the central nervous system and
      the kidneys. The first signs of neurotoxicity are difficult to recognize because
      the effects are very unspecific and show a high inter-individual variation.
      Patient and dentist are exposed to mercury from food, by amalgam restorations and
      by mercury vapor in the dental office. There is no general concensus about the
      amount of mercury released from amalgam. The estimations on the daily mercury
      uptake after release from amalgam vary between 2 en 10 micrograms. In comparison
      to the daily uptake of 10 micrograms from food, the contribution from amalgam is
      substantial, but based on a tolerable daily uptake of 30 micrograms mercury for
      the general population, there still seems to be no reason for a health concern.
      However, an interdisciplinary approach is required to determine the dose-response
      relationship more accurately. In addition, based on measurements of the internal
      exposure of the dental team, it can be concluded that mercury vapor seems to be
      no significant health risk for the personnel in most dental offices.

PMID- 11822125
TI  - [Amalgam. VI. Allergy to mercury in dental materials; oral and systemic
      reactions].
AB  - Allergy for mercury in dental alloys can be responsible for the induction of
      allergic contact stomatitis. Evidence is also available for a role of mercury
      sensitization in the pathogenicity of oral lichen planus in particular. Aspects
      related to the development of allergic processes in the oral cavity are
      summarized. Allergy for mercury as the cause of oral mucosal reactions is rather
      rare in spite of the frequent use in dental amalgam, but probably underestimation
      of the incidence should be considered. Recent views with respect to the role of
      mercury as allergen in allergic contact stomatitis, oral lichen planus, the so
      called Burning mouth syndrome and in systemic allergic reactions are summarized.
      Immunologic aspects in the pathogenesis are briefly discussed. Especially in
      cases in which the site or oral lesions is opposite to the dental alloy it is
      important to establish sensitization for mercury by use of epicutaneous path
      testing. When a positive test to mercury is obtained replacement of mercury
      containing alloys should be considered.

PMID- 11822126
TI  - [Vital reaction after orthodontic treatment of root fracture. Orthodontic case
      report].

PMID- 11822127
TI  - [Amalgam. IV. Metabolism of mercury].
AB  - After absorption in the body by four ways, each type of mercury undergoes a
      specific metabolism. Elementary mercury as mercury vapour becomes rapidly
      oxidized to Hg2+ and, afterwards, is metabolized as an inorganic mercurial
      compound. From the blood circulation mercury reaches target organs like the
      kidneys, the central nervous system, the liver and the hypophysis, in which
      mercury accumulates. The retention time varies by organ and is longest in the
      brain. Mercury is mainly eliminated with urine and faeces, to a lesser degree
      with transpiration and mother's milk and sometimes by respiration.

PMID- 11822128
TI  - [Is my patient infected with HIV?].

PMID- 11822129
TI  - [Amalgam. X. Glass-ionomer cement: a biocompatible substitute for amalgam?].
AB  - The biocompatibility of glass-ionomer depends upon the components released. The
      consequences of this releasing for the health of the pulp seem to be moderate,
      provided that there is a rather thick layer of dentin (> 1 mm) to protect the
      pulp. Glass-ionomer shrinks upon setting, but it adheres to the dental hard
      tissues. Yet, bacteria are found along and underneath the material. Systemic
      effects due to toxicity and allergy are largely unknown, possibly because glass
      ionomer is a recent, as yet insufficiently investigated material.

PMID- 11822130
TI  - [The reorganization in the health care arena: what are the consequences for
      dentistry?].

PMID- 11822131
TI  - [New materials and their future].

PMID- 11822132
TI  - [Colorimetry: measurement to determine tooth color].

PMID- 11822133
TI  - [Lasers in jaw surgery and dentistry].

PMID- 11822134
TI  - [Implantations and their future].

PMID- 11822135
TI  - [New developments in periodontology].

PMID- 11822136
TI  - [Dentures for the elderly. A balancing act].

PMID- 11822137
TI  - [New perspectives for patients with mouth cancer?].

PMID- 11822138
TI  - [Undiagnosed swelling of the bottom lip].

PMID- 11822139
TI  - [Amalgam. IX. Substitute for amalgam: durability of composite restorations].
AB  - In order to answer the question whether composite is an adequate amalgam
      substitute, both the biocompatibility and the longevity of the composite
      restorations are of major importance. In the newly developed composites the wear
      problem has been overcome, in particular by the modification of the filler. Yet,
      large restorations will often fail within four years. A relatively large number
      of the composite restorations will show shortcomings, for instance surface
      roughness and shortcomings in the marginal adaptation, but the same are true for
      restorations made of amalgam. Longevity data are shown, but for the newest
      products five-year in vivo data are lacking.

PMID- 11822140
TI  - [A new face?].

PMID- 11822141
TI  - [Color recognition in the front].

PMID- 11822142
TI  - [Colorful and nice restoration in the (pre)molar area].

PMID- 11822143
TI  - [Better no tooth than a long tooth? Esthetics and periodontology].

PMID- 11822144
TI  - [Esthetics in orthodontics].

PMID- 11822145
TI  - [An harmonic looking face by rearrangement of the jaws].

PMID- 11822146
TI  - [Esthetic possibilities for the toothless patient].

PMID- 11822147
TI  - [Extreme beauty].

PMID- 11822148
TI  - [Misleading pain complaints due to herpes zoster].

PMID- 11822149
TI  - [Amalgam. VIII. Substitute for amalgam: the biocompatibility of composite
      restorations].
AB  - Because of cosmetic reason and fear of mercury released from amalgam, many
      patients prefer tooth coloured restorations, i.e. made of composite. However,
      like in the case of amalgam, one has to ask whether composite is a biocompatible
      material. Whether or not biotransformed, all components of composite may be
      released. Damage to the pulp of teeth restored with composite has been proven to
      be due to bacterial leakage, which in turn is a consequence of the shrinkage
      associated with the material itself. Rarely local and general symptoms of allergy
      appear, but they may become more common, as is already the case with the dentists
      and their assistants. Toxicity of composite seems unlikely in view of their
      smallness and carcinogenicity for the time being is excluded.

PMID- 11822150
TI  - ["Please straighten 38 and 48"].

PMID- 11822151
TI  - [Amalgam. V. A durable restoration material?].
AB  - The longevity of amalgam restorations is limited due to several shortcomings.
      Some of these may be influenced by the dentist. Important are the indications
      that form the basis to replace restorations.

PMID- 11822152
TI  - ['Please remove 48'].

PMID- 11822154
TI  - Eye on HDA's Dental Samaritans.

PMID- 11822153
TI  - How to de-stress your stress glands.

PMID- 11822155
TI  - Emotional stress in dentistry.

PMID- 11822156
TI  - A historical and clinical perspective of maxillary distalization in Class II
      malocclusions.

PMID- 11822157
TI  - Facial cosmetics: the key to great orthodontic treatment.

PMID- 11822158
TI  - The route to knowledge.

PMID- 11822159
TI  - Class II malocclusion: why, when and how to treat this anomaly in mixed dentition
      with fixed functional appliances.

PMID- 11822160
TI  - [Main point publication. Foot-and-mouth disease].

PMID- 11822161
TI  - [Occurrence of foot and mouth disease--a historical survey].
AB  - FMD--the most economically significant animal disease in the world during the
      last two centuries--has caused the last great panzootic from 1965 to 1967 in
      Europe. Since then it has become possible to eradicate centres of the epidemic
      still being present on the continent, mainly by means of the annual mass
      vaccination of cattle combined with rigid antiepizootic measures which include
      culling of infected animals. During the years after however there has been
      sporadic outbreaks again and again. They were mainly caused by virus that escaped
      from FMD laboratories and by the application of vaccines with residual
      infectiousity but also to an increasing extent they resulted from virus brought
      in from endemic regions of the world. The now as before high incidence of FMD in
      Asia and in wide parts of Africa and South America--after all 71 countries in
      these regions have been affected by outbreaks of FMD, the classic carrier
      disease, from 1998 to 2000--resulted in the spread of virus over far distances
      due to the globalization of world trade and the increasing traveling favoured by
      modern traffic facilities. Since 1980 in Europe particularly virus strains from
      the Middle East but also from other parts of Northern Africa and Asia have
      dominated the epidemiological situation such as the current epizootic in the
      United Kingdom and the outbreaks resulting from in three other member states of
      the European Union. In accordance with the EU guidelines the control of occurring
      outbreaks is exclusively carried out by stamping out. The limits of this
      procedure have become clearly obvious during the current epizootic in Britain.
      The use of emergency vaccination in the Netherlands shows a practicable
      alternative to the excessive mass culling of both infected animals and those
      being suspected of. The plurality and variability of the causative agent require
      a permanent observation of the epidemiological situation and of the virus strains
      involved in order to prevent the disease and to ensure the diagnosis and the
      topicality of the vaccines being available in the vaccine banks. Long-term
      success in the global combat against FMD can only be achieved on the basis of
      close international co-operation intended to restrain the disease significantly
      in the still endemically infected regions.

PMID- 11822162
TI  - [Clinical picture and differential diagnosis of foot and mouth disease in
      cattle].
AB  - Foot-and-mouth disease (FMD) in cattle is characterized by the formation of
      vesicles and erosions in the mouth, teats and feet. Despite extremely high
      morbidity, mortality in adults is usually very low, however up to 50% of calves
      dies due to cardiac involvement or secondary infections. This paper describes the
      signs of FMD in cattle as well as those of other diseases which causes similar
      lesions in this species.

PMID- 11822164
TI  - [Clinical signs and differential diagnosis of foot and mouth disease in pigs].
AB  - FMD in pigs is primarily a foot disease. It is dominated by rather painful
      formation of vesicles in the epidermis of the feet (coronary band, interdigital
      clefts, bulbs) combined with severe lameness. Complications will be seen as
      detachment of the hoof and secondary infection of disrupted aphthae which may
      cause purulent arthritis of the pedal joint. Concerning differential diagnosis
      are to be considered all cases of acute lameness, vesicle-formation as typical
      lesions of exudative epidermites of pemphigus in the course of infections with S.
      hyicus or S. aureus as well as degenerative changes after selenium-intoxication,
      specially near the coronary band, sometimes linked with exungulation.

PMID- 11822163
TI  - [Foot and mouth disease in sheep and goats].
AB  - Small ruminants play an important role in the epidemiology and transmission of
      Foot-and-Mouth Disease (FMD). The main reasons therefore are: FMD is difficult to
      diagnose as infected sheep not always show typical clinical symptoms or as the
      cardinal signs mimicked other diseases. Sheep and goats may be carriers. Infected
      herds which practice transhumance or are nomadic can spread the infection to
      other herds long before diagnose of the disease is established. Shipping and
      trade with live sheep and goats is much more common world wide than in other FMD
      susceptible species. Lack of registration of all sheep and goat herds (especially
      of small hobby herds) and lack of individual identifications signs (ear tags) may
      result in incomplete control measurements under FMD conditions. Basing on
      published experiences with the actual FMD epidemic in the UK and basing on the
      own experiences with the restrictions to prevent from spreading of the FMD from
      the UK to Germany suggestions for future disease control are made.

PMID- 11822165
TI  - [Diagnosis of foot and mouth disease].
AB  - Because foot-and-mouth disease has the potential for an explosive spread, instant
      and reliable diagnosis is of special importance. In this article the clinical
      examination, types and shipment of samples as well as the current methods of
      laboratory diagnosis by detection of FMD-virus, antigen, nucleic acid and
      antibodies are reviewed. Special emphasis is laid on the differentiation between
      vaccinated and infected animals, in respect to conventional as well as novel
      vaccines.

PMID- 11822166
TI  - [Persistence of FDMV and its effects on disease control strategies].
AB  - It is well-known that foot-and-mouth disease virus (FMDV) causes a persistent
      infection, lasting for more than 28 days, in cattle, sheep, goat as well as some
      other ruminant species, but not in pigs. Although convincing evidence for virus
      transmission is missing, these carrier animals have to be considered as a
      potential risk of infection. Some aspects of FMDV persistence are presented and
      discussed with regard to disease control strategies.

PMID- 11822167
TI  - [FMD and international trade relations--conditions and consequences].
AB  - The outbreak of foot-and-mouth disease in several member states of the European
      Union this year made the risks linked to this epidemic pretty clear to the
      public. In this connection, the possibility of vaccinations was controversially
      discussed not only among experts. Therefore it has to be taken into consideration
      that every kind of vaccination leads to economic consequences, which have to be
      taken into account when making such a decision. It is an illusion assuming that
      there will be a return to prophylactic vaccination. However in certain situations
      such emergency vaccination have to be available as an additional measure of
      control. Because of present decisions of the European Commission any consequences
      connected therewith are known. Thereby the EU regulations coincide with those of
      the Office International des Epizooties (OIE) and make the extent of restrictions
      after vaccination calculable. The assessment leads to the conclusion that
      preventive measures, rapid and successful eradication of FMD outbreaks as well as
      the option of emergency vaccination have to be followed as an overall conception.

PMID- 11822168
TI  - [Vaccination against foot and mouth disease: current state and perspectives].
AB  - Foot-and-mouth disease (FMD) is endemic in many parts of the world and poses a
      permanent threat for cloven-hoofed animals in all countries. The available
      vaccines against FMD are safe and efficacious. Combat of FMD by vaccination is
      controversial in currently FMD-free countries including the ones of the European
      Union. The article summarizes our knowledge concerning production and use of
      vaccines, virus persistence, differentiation between vaccinated and infected
      animals, vaccination programs and perspectives of vaccine development.

PMID- 11822169
TI  - [Veterinary medicine in the media society--science and media in relation to FMD].
AB  - The outbreak and explosive spread of foot-and-mouth disease in the European Union
      brought about an intense discussion in the media. FMD was an outstanding media
      topic in Germany. But the scientific experts of veterinary medicine had no
      prominent role in this public debate. The reason for this fact seemed to be a
      lack of competence to present themselves and their knowledge in the media arena.
      The scientists should try to fit themselves in the media society by training
      their communication competence.

PMID- 11822170
TI  - Synthesis and cytotoxicity of bis(benzo[g]indole-3-carboxamides) and related
      compounds.
AB  - A series of bis(benzo[g]indoles) bridged by CX-(CH2)nN(Me)(CH2)n-CX (X = O, S,
      H2; n = 2,3) was synthesized as bifunctional antitumor agents and evaluated for
      cytotoxic activity against diverse human cancer cell lines by the National Cancer
      Institute. The parent compounds 2a,b exhibited a good level of activity and
      derivates 2c-g,i,k demonstrated significant inhibitory effects, all with IC50
      values in the low micromolar range. The thioamide analogue 2j showed less
      potency. It is interesting to note that introduction of substituents on the
      benzene ring of the benzo[g]indole portion of 2a,b did not affect activity, with
      the only exception of the 7,8-dichloro derivative 2h which became less potent.
      One member of this series, 2i, was then tested in the hollow fiber cell assay to
      evaluate, in a preliminary fashion, its in vivo antineoplastic activity.
      Molecular modelling studies were performed on amide 2a and thioamide 2j to
      explain the loss of activity of 2j as to 2a. Finally, compound 2a behaved as a
      typical DNA intercalating agent, as judged from viscosity measurements with
      Poly(dA-dT)...poly(dA-dT).

PMID- 11822171
TI  - Synthesis and biological properties of C-2, C-8, N-9 substituted 6-(3
      chloroanilino)purine derivatives as cyclin-dependent kinase inhibitors. Part II.
AB  - In this study, C-2, C-8, N-9 substituted 6-(3-chloroanilino)purine derivatives
      were synthesized and their inhibitory effects on cyclin-dependent kinases (CDK2,
      4) as well as their cytotoxicities were evaluated. The effects of substituents at
      the C-2, C-8, and N-9 positions of the substituted purine were investigated.
      Among the compounds tested, [6-(3-chloroanilino)-2-(2-hydroxymethyl-4
      hydroxypyrrolidyl)-9- isopropylpurine] (4h) was the most active inhibitor of CDK2
      with IC50 of 0.3 microM, i.e. a two-fold increased inhibitory activity as
      compared to roscovitine. Results from structure-activity relationship studies
      should allow the design of more potent and selective CDK2 inhibitors, which may
      provide an effective therapy for cancer or other CDK-dependant diseases.

PMID- 11822172
TI  - Synthesis and biological investigations of 5-substituted pyrimidine nucleosides
      coupled to a dihydropyridine/pyridinium salt redox chemical delivery system.
AB  - The syntheses, antiviral activities, and partition coefficients (P) of 3'-O-(1
      methyl-1,4-dihydropyridyl-3-carbonyl)-coupled nucleosides are described. These
      novel compounds were designed in an effort to enhance the lipophilicity, and
      thereby the delivery to the CNS, without compromising the anti-HSV-1 activity of
      the parental nucleosides. We have previously reported the synthesis of 3'-O-(1
      methyl-1,4-dihydropyridyl-3- carbonyl) analogs of 5-iodo-(5), 5-vinyl-(6), and
      (E)-5-(2-iodovinyl)-2'-deoxyuridines (7). We now report the synthesis of 5-iodo
      3'-O-(1-methyl-1,4-dihydropyridyl-3- carbonyl)-5'-O-acetyl-2'-deoxyuridine (15)
      and 3'-O-(1-methyl-1,4-dihydropyridyl-3-carbonyl)-2'-deoxyuridine (17).
      Quarternization of the 3'-O-(3-pyridylcarbonyl) compounds (10,12) using
      iodomethane afforded the corresponding 1-methyl pyridinium salts (13,14) which
      were reduced with sodium dithionite to yield the corresponding 3'-O-1-methyl-1,4
      dihydropyridyl-3-carbonyl compounds (15,16). The deprotection of 3'-O-(1-methyl
      1,4-dihydropyridyl- 3-carbonyl)-5'-O-t-butyldimethylsilyl-2'-deoxyuridine (16)
      with Bu4N+F- afforded 3'-O-(1-methyl-1,4-dihydropyridyl-3-carbonyl)-2'
      deoxyuridine (17). Compounds 5-7 and 15 were evaluated for their antiviral
      activity in vitro against HSV-1, HSV-2, HCMV, and VZV, and were found to retain
      anti-HSV-1, HSV-2 and VZV activity as compared to their parental nucleosides (1
      3). In addition, the cellular toxicity of 3'-O-(1-methyl-1,4-dihydropyridyl-3
      carbonyl)-coupled compounds (5-7 and 15) was found to be lower than the parent
      nucleosides. The lipophilicity of compounds (5-7,15,17) are enhanced
      substantially, compared to the parent nucleosides, as indicated by an increase in
      corresponding P values (1-octanol-water) upon replacement of the C-3' hydroxyl by
      1-methyl-1,4-dihydropyridyl-3-carbonyl moiety.

PMID- 11822173
TI  - 1,4-dioxane-fused 4-anilinoquinazoline as inhibitors of epidermal growth factor
      receptor kinase.
AB  - The 4-anilinoquinazoline PD 153035 (1) is a potential antitumor agent which acts
      by inhibiting tyrosine kinase activity of epidermal growth factor receptor (EFGR)
      via competitive binding at the ATP site of enzyme. A series of cyclic analogues
      of PD 153035 bearing the 1,4-dioxane ring was prepared by reaction of 6-chloro
      derivative 5 with several aniline nucleophiles. These were evaluated for their
      ability to inhibit the EGFR kinase and the growth of primary human tumor cell
      cultures. All of the new 4-anilinoquinazolines exhibited less potency than PD
      153035 against EGFR kinase. However, compounds 2b, 2c, 2e, 2g, and 2h showed
      higher inhibitory activities than PD 153035 against the growth of A431 tumor cell
      line. The compound 2b containing 3-chloroaniline ring was as potent as PD 153035
      against EGFR kinase and showed about 5.4-fold better potency than PD153035 in the
      inhibition of growth of A431 cell line with good selectivity.

PMID- 11822174
TI  - Synthesis and antimicrobial activities of 5-fluoro-1,2,6-trisubstituted
      benzimidazole carboxamide and acetamide derivatives.
AB  - Some 5-fluoro-6-substitute-1 H-benzimidazole-2-carbamates (12a-e), 5-fluoro-6
      substituted 1H-benzimidazole-2-acetate (13a-e) and 2-acetamide (14a-f)
      derivatives, 2-acetamido-5-fluoro-6-(morpholin-4-yl)-1-propyl-1H-benzimidazole
      (15), and 1-cyclopropyl-2-ethyl-5-fluoro-6-(4-methylpiperazin-1-yl)- 1H
      benzimidazole (16) were synthesized, and their antimicrobial and antifungal
      activities evaluated. Compound 12c exhibited the best activity against Candida
      albicans.

PMID- 11822176
TI  - Alternative risk transfer. One response to a hardening insurance market.

PMID- 11822175
TI  - Anticonvulsant activity of reaction products of 5,5-diphenylhydantoin with
      substituted methylene bromides.
AB  - Some derivatives of 5,5-diphenylhydantoin (phenytoin) were synthesized by the
      alkylation of phenytoin with substituted methylene bromides. The hydantoins were
      evaluated for possible anticonvulsant activity in the maximal electroshock (MES)-
      and subcutaneous pentylenetetrazole (ScMet)-induced seizures and for
      neurotoxicity in the rotorod test in mice and rats.

PMID- 11822177
TI  - Relicensure requirements. Deadline January 31st.

PMID- 11822178
TI  - Bioterrorism. Yesterday's threat, today's reality.

PMID- 11822179
TI  - Anthrax Q & A.

PMID- 11822180
TI  - Anthrax: what you should know.

PMID- 11822181
TI  - Study reveals levels of burnout among surgeons.

PMID- 11822184
TI  - Can a Medicare+Choice makeover attract plans, providers?

PMID- 11822186
TI  - Employers looking for system changes to combat cost hikes.

PMID- 11822182
TI  - Doctor-patient relationships can mean professional satisfaction.

PMID- 11822187
TI  - Will cost hikes bring employers back to capitation contracts?
AB  - Concerned about the recent increases in health care costs, employers are once
      again looking for solutions. Providers and plans that know what employers are
      thinking can structure their offerings to meet the need.

PMID- 11822188
TI  - CalPERS backs away from direct contracting.

PMID- 11822189
TI  - Disease management program saves plan $900 per person in first year.

PMID- 11822190
TI  - Could blended payments broaden use of capitation?
AB  - If capitation is going to return as a viable health care mechanism, some changes
      will be needed. Here are suggestions for a blended payment approach that could do
      the trick.

PMID- 11822191
TI  - Cytochemical and molecular biological aspects of the pituitary and pituitary
      adenomas--cell differentiation and transcription factors.
AB  - The anterior pituitary is composed of several cell types, each responsible for
      the production of specific hormones. Each hormone secreting cells is defined by
      the activation of its respective hormone genes in a temporally and spatially
      regulated manner. Recent development in cytochemistry and molecular biology have
      provided various aspects of human pituitary adenomas, i.e., functional
      differentiation and classification. The molecular factors that determine hormone
      production have now been identified as transcription factors. Many novel
      transcription factors that play a role in anterior pituitary development are
      implicated. In this review, we focus on the transcriptional factors roles on
      functional differentiation of the pituitary cells and adenomas and the
      contribution of cytochemistry and recent development in molecular biological
      techniques.

PMID- 11822192
TI  - Disability methodology redesign: considerations for a new approach to disability
      determination.
AB  - Disability determination meets important societal needs, involving billions of
      dollars and millions of people every year. However, disability determination
      decisions often are incorrect, and the high proportion of decision appeals and
      reversals creates additional administrative expense and difficulty for the people
      that the disability determination system is intended to support. Projects funded
      by the United States Social Security Administration explored these issues and
      developed new conceptual models and tools to improve the accuracy and fairness of
      disability determination. This paper provides an introduction to the projects and
      the papers in this special issue of the Journal of Occupational Rehabilitation.

PMID- 11822193
TI  - Development of new methods to determine work disability in the United States.
AB  - The development of new methods to determine work disability for the United States
      Social Security Administration is described, including the fiscal and
      administrative background to the current and proposed methods. An introduction to
      the current disability determination process and description of its status is
      followed by a description of the original proposed plan for redesign of the
      process. In response to this plan, the authors participated in several research
      projects. An overview of some of the key research projects performed to improve
      the Social Security Administration disability determination process is provided.

PMID- 11822194
TI  - Development of the Functional Assessment Taxonomy.
AB  - The development of the Functional Assessment Taxonomy is described and the
      taxonomy is presented. The taxonomy provides a method to classify and organize
      constructs that are used to assess the functional abilities of people with
      medical impairments to determine work disability. The taxonomy has 131 constructs
      that are organized into 33 conceptual factors that are nested in 5 domains. Each
      construct is defined and is categorized in terms of the work disability model and
      the unit of analysis that is commonly used to measure the construct. The use of
      the taxonomy in the Disability Methodology Redesign Project is described. Other
      possible uses for the taxonomy are presented.

PMID- 11822195
TI  - Development of a database of functional assessment measures related to work
      disability.
AB  - The development of the Functional Assessment Measures Database is described. The
      database provides a method to organize and search for measures that are used to
      assess the functional abilities of people with medical impairments to determine
      work disability. The project identified 4,200 different measures that are used in
      the functional assessment of persons with disability across the life span, 812 of
      which are used to evaluate adults in terms of work disability. The database has
      3,033 scales that are found in 633 measures. In the database, each measure is
      described and is linked to at least one functional assessment construct. The use
      of the database in the Social Security Administration Redesign Project is
      described. Other possible uses for the database are presented.

PMID- 11822196
TI  - Functional assessment taxonomy relevant to low-back impairments.
AB  - A taxonomy of functional assessment constructs was developed to help the Social
      Security Administration refine the measurements of work disability. This report
      addresses content validity of the new taxonomy by examining the relevance of its
      constructs to a specific disability, and by examining the relationship between
      these constructs and constructs in other taxonomies. Seven experts linked the new
      taxonomy to consequences of low-back impairments. The selected constructs were
      compared to those reported independently by patients (Harper AC, Harper DA,
      Lambert L, Andrews HB, Lo SK, Ross FM, Straker LM. Pain 1992; 50(2): 189-195).
      The International Classification of Impairments, Disabilities and Handicaps
      served to bridge the two exercises. The findings reveal that it is feasible to
      use the taxonomy to define the impact of a specific disability and consequently
      link it to a set of standard measurements. Low-back impairments may be best
      assessed through measures of physical functional limitations, vocational impact,
      and interpersonal and emotional behavior. The study did not yield cognitive and
      intellectual measures that were relevant to this impairment.

PMID- 11822197
TI  - Unique issues in assessing work function among individuals with psychiatric
      disabilities.
AB  - With the admission of people who experience psychiatric disabilities in the state
      federal vocational rehabilitation system and the Social Security disability rolls
      in the 1960s, assessment of their capacity to work has been a major concern.
      Given the rising rates of claims for psychiatric disability in both the public
      and the private sectors, and the disappointing employment outcomes of people with
      psychiatric disabilities compared to those with other disabilities, there have
      been numerous initiatives to accurately assess their employment potential.
      Historically, such assessment within the Social Security Administration has
      relied upon evaluation of a person's medical impairment, but numerous studies
      suggest a weak relationship between measures of psychiatric diagnosis or symptoms
      and work outcome. Efforts have been undertaken to identify valid and reliable
      methods of assessing the ability of people with psychiatric disabilities to work.
      The authors review (a) methods of assessing work function for this population,
      and (b) the literature on predictors of work functioning and the nature of
      psychiatric disability, and suggest implications for disability determination
      policies and for future research.

PMID- 11822198
TI  - Effects of thyroid hormones on inner mitochondrial membrane fluidity.
AB  - Authors studied the effects of thyroid hormones and their diasteroisomers and 3,5
      diiodothyronine (LT2) on the fluidity properties of inner mitochondrial membrane
      (IMM) by specifical fluorescent probe for the internal zone of biological
      membranes, the 1,6-diphenyl-1,3,5-hexatriene (DPH). The studied parameters are
      Arrhenius and Perrin plots. The DPH shows a decreased fluorescence quenching in
      the presence of both T3 and T4. The maximum effect is observed with 2 nM LT2. LT2
      is more effective than LT3 in the central zone. The data confirm the selective
      action of LT3 and LT4 on IMM fluidity.

PMID- 11822200
TI  - Prophylaxia of cystine calculosis by alpha-mercaptopropionyl-glycine administered
      continuously or every other day.
AB  - We determined the efficacy of alpha-mercaptopropionyl-glycine administered in a
      low dosage continuously or every other day for prophylaxis of cystine calculosis.
      Two homozygous cystinuric patients with previous calculosis and renal unilateral
      hypoplasia and been given preventive treatment with alpha-mercaptopropionyl
      glycine continuously administered in a low dosage (1.5-4 mg Kg-1 day-1 for 14 1/2
      years and 10(-4) mg Kg-1 day-1 for 9 years respectively). Neither calculosis, nor
      side effects were observed. Subsequently, the patients were given 4 mg Kg-1 of
      the drug every second day for 1 and 1-2 years respectively without calculosis or
      side effect being observed. A low dosage of alpha-mercaptopropionyl-glycine(1.5-4
      mg Kg-1 day-1) supplied continuously or, for a short time, 4 mg Kg-1 day-1
      supplied every other day can be effective in the prophylaxis of cystine
      nephrolithiasis in some homozygous patients with renal unilateral hypoplasia,
      with lower risk of side effects.

PMID- 11822199
TI  - Variations of ATP content in V79 cells treated with crude toxins of--Aequorea
      aequorea (Cnidaria: Hydrozoa) and Rhizostoma pulmo (Cnidaria: Scyphozoa). A
      preliminary study.
AB  - The toxicity of Cnidaria exerts a noticeable influence on some human activities,
      such as fishery and bathing, and on public health. As toxins of Mediterranean
      Cnidaria are located in nematocysts and in tissues, in this study the influence
      of crude toxins (nematocyst and surrounding tissue venom) extracted from the
      jellyfish Aequorea aequorea and Rhizostoma pulmo on ATP content of cultured V79
      cells was assessed. Using the crude toxin of A. aequorea an increase of ATP
      levels in treated cells was noted; highest values (41.2 10(-7) mM/ml after 180
      min treatment) were reached using the highest dose. Otherwise, a generalized
      decrease of ATP levels was observed treating cells with crude toxin of R. pulmo;
      recorded values showed the complete depletion of cell ATP at 115 min treatment
      with the highest dose. A statistical significance was recorded between treatment
      times and between doses using crude toxin of R. pulmo, and only between treatment
      times for A. aequorea.

PMID- 11822201
TI  - Methyleugenol and eugenol variation in Ocimum basilicum cv. Genovese gigante
      grown in greenhouse and in vitro.
AB  - The variation of the two main aromatic compounds in Ocimum basilicum cv Genovese
      Gigante grown in greenhouse and "in vitro" was analyzed. The content of
      methyleugenol and eugenol was correlated to the plants' height rather than to the
      plants' age and the growth site. Particularly, methyleugenol was prevalent in
      plants up to 6.5 cm, as plants grew it was replaced by eugenol that was dominant
      in taller plants. Analysis of basil 20 cm in height showed that methyleugenol is
      prevalently localized in the low part while eugenol is prevalent in the upper
      part of the plant. Moreover, a chronic and acute toxicity of methyleugenol was
      evidentiated in an assay using chicken embryos.

PMID- 11822202
TI  - Knowledge of brain memory codification as a challenge for the third millennium.

PMID- 11822203
TI  - Influence of static magnetic fields on cell viability, necrosis and apoptosis.

PMID- 11822204
TI  - Epibiotic bacteria in the marine ecosystem.

PMID- 11822205
TI  - Interaction between electromagnetic waves and auditory organs.

PMID- 11822206
TI  - Violent and aggressive behaviors in youth: a mental health and prevention
      perspective.
AB  - Aggressive behavior and violence leading to disciplinary and legal difficulties
      have reached epidemic proportions among our youth. The severity of problems and
      social and economic costs to society have increased markedly. In this article,
      the authors review the risk factors, situational concerns, and warning signs that
      are important in predicting school violence and in designing effective prevention
      and early intervention efforts. They then describe programs with which they are
      involved as mental health professionals that appear to be extremely promising and
      applicable to other communities. The prevention and intervention programs are
      distinctive in that they involve collaborations with law enforcement, including
      the police and criminal sheriff, and the juvenile court as well as parents and
      schools in their efforts to promote positive development. These clinical,
      educational, and public policy approaches offer mental health professionals
      increased opportunities to be of help in this critical area.

PMID- 11822208
TI  - The impact of coping on the relation between symptoms and quality of life in
      schizophrenia.
AB  - The relation between severity of symptoms and level of quality of life in
      schizophrenia is not strong. This situation may be explained by the hypothesis
      that the relation is moderated by ways of coping which are known to overcome
      stress. The main objective of the study was to evaluate this hypothesis by
      assessing the relations between positive and negative symptoms, problem-focused
      and emotion-focused ways of coping, and various domains of quality of life in a
      group of psychiatric outpatients diagnosed with schizophrenia. Subjects were
      recruited from a community mental health center. Fifty-eight adult outpatients
      diagnosed with schizophrenia who gave informed consent were assessed cross
      sectionally with the Positive and Negative Syndrome Scale (PANSS), the Ways of
      Coping Checklist, and the Wisconsin Quality of Life Index. Negative symptoms were
      inversely related to activities of daily living, and positive symptoms were
      directly related to distress. There were no other significant relations between
      symptoms and quality of life. Problem-focused and emotion-focused coping did not
      moderate the relation between symptoms and quality of life. Further study is
      required concerning coping in schizophrenia.

PMID- 11822207
TI  - Increased alcohol use in a treatment sample of Oklahoma City bombing victims.
AB  - Research examining alcohol use in disaster victims has yielded conflicting
      results. This study of 43 acknowledged alcohol users, taken from a nonrandom
      volunteer sample of Oklahoma City bombing victims receiving support services,
      revealed relationships between increased alcohol use and a number of variables-
      injury, retrospectively reported initial reaction to the explosion, grief, and
      posttraumatic stress symptomatology. The findings suggest that if alcohol use was
      motivated by an attempt to alleviate symptoms, it was not effective, as evidenced
      by an association between increased alcohol use and functional impairment.
      Increased alcohol consumption may present a problem in disaster victims months
      after exposure to trauma. Therefore, the use of alcohol should be routinely
      assessed in those who remain symptomatic over time.

PMID- 11822209
TI  - Obsessive-compulsive symptomatology: a goal-directed response to anticipated
      traumatization?
AB  - Through the use of case material, this article traces the evolution of one
      individual's potentially adaptive response to traumatic stressors into obsessive
      compulsive illness. The following discussion offers a conceptualization of trauma
      induced obsessive-compulsive symptomatology that presents the phenomena as a
      predictable pattern of traumatic antecedents, anticipatory arousal, and a
      subsequent goal-directed motivational state to prevent anticipated
      traumatization. However, this hypothesis depends upon an expansion of our
      diagnostic understanding of traumatization to include interpersonal threat and
      how it might be symbolized by the individual seeking relief.

PMID- 11822210
TI  - The contribution of early traumatic events to schizophrenia in some patients: a
      traumagenic neurodevelopmental model.
AB  - The current diathesis-stress model of schizophrenia proposes that a genetic
      deficit creates a predisposing vulnerability in the form of oversenstivity to
      stress. This model positions all psychosocial events on the stress side of the
      diathesis-stress equation. As an example of hypotheses that emerge when
      consideration is given to repositioning adverse life events as potential
      contributors to the diathesis, this article examines one possible explanation for
      the high prevalence of child abuse found in adults diagnosed schizophrenic. A
      traumagenic neurodevelopmental (TN) model of schizophrenia is presented,
      documenting the similarities between the effects of traumatic events on the
      developing brain and the biological abnormalities found in persons diagnosed with
      schizophrenia, including overreactivity of the hypothalamic-pituitary-adrenal
      (HPA) axis; dopamine, norepinephrine, and serotonin abnormalities; and structural
      changes to the brain such as hippocampal damage, cerebral atrophy, ventricular
      enlargement, and reversed cerebral asymmetry. The TN model offers potential
      explanations for other findings in schizophrenia research beyond oversensitivity
      to stress, including cognitive impairment, pathways to positive and negative
      symptoms, and the relationship between psychotic and dissociative symptomatology.
      It is recommended that clinicians and researchers explore the presence of early
      adverse life events in adults with psychotic symptoms in order to ensure
      comprehensive formulations and appropriate treatment plans, and to further
      investigate the hypotheses generated by the TN model.

PMID- 11822211
TI  - Stress-induced enhancement of auditory startle: an animal model of posttraumatic
      stress disorder.
AB  - An innovative animal model of posttraumatic stress disorder (PTSD) is proposed in
      which nonhabituation of the acoustic startle response is developed in rats
      subsequent to tailshock exposure. Subjects (n = 31) received 30 minutes of
      intermittent tail shock on 2 days followed by exposure to the tailshock apparatus
      on the third day. Compared to baseline startle reactions, 9 of 31 tailshock
      exposed rats developed nonhabituation of startle response reactions during the
      subsequent 3 weeks of testing. No control rats developed nonhabituation of
      startle reactions over a similar time period. These data suggest that this system
      models useful aspects of clinical PTSD emphasizing nonhabituation of startle
      reactions as a dependent variable. The method consistently identifies a subgroup
      of rats that develop persistent nonhabituation of startle in response to a
      tailshock-stress paradigm.

PMID- 11822212
TI  - Clinical responsibility and client autonomy: dilemmas in mental health work at
      the margins.
AB  - Mental health outreach to homeless persons requires practice standards for cases
      in which clinical assessment and client autonomy conflict. After reviewing the
      principles of mental health outreach and presenting case examples, conditions and
      boundaries within which outreach workers negotiate the clinical
      responsibility/client autonomy dilemma are discussed. Guidelines to support sound
      clinical practice while respecting client autonomy are also discussed.

PMID- 11822213
TI  - Complementary spiritual beliefs in the Latino community: the interface with
      psychotherapy.
AB  - A model involving a dynamic spectrum of belief by Latinos in the spiritual
      traditions of Santeria and Espiritismo is proposed as replacement for the more
      static prevalence model. The issue of clinical responsiveness to such material is
      examined and illustrated, and implications for research and practice are
      discussed.

PMID- 11822214
TI  - Psychological model for judicial decision making in emergency or temporary child
      placement.
AB  - In emergencies, family court judges must often make rapid decisions, without
      benefit of thorough information, that have significant impact on people's lives.
      Action-oriented research was used to develop a model that would bring
      psychosocial factors to the legal system for the purpose of enhancing the
      judicial decision-making process in emergency and temporary child placement
      cases.

PMID- 11822215
TI  - Attributions of responsibility for children's mental health problems: parents and
      professionals at odds.
AB  - Surveys of 102 mothers of inner-city youths with mental health problems and their
      clinicians examined discrepancies in mothers' and professionals' causal and
      solution attributions for the children's problems. Greater causal responsibility
      was attributed to mothers by professionals than by mothers, while they agreed on
      the children's responsibility. They disagreed about their respective solution
      responsibilities, though agreeing that causally responsible children should help
      with solutions. Mothers considered many more community resources for solutions
      than did professionals. Implications for improvement of services to urban
      children are discussed.

PMID- 11822216
TI  - Interactive effects of individuation, family factors, and stress on adolescent
      alcohol use.
AB  - A prospective, school-based study of increasing alcohol use in a multi-ethnic
      sample of 7,540 adolescents showed that the effects of stress, family conflict,
      and parental monitoring were differentially moderated by two modes of
      individuation. The effects of stress were moderated by ethnic status and
      individuation. Implications for prevention and intervention are discussed.

PMID- 11822217
TI  - The mental health and biosocial context of help-seeking in longitudinal
      perspective: the Midtown Longitudinal Study, 1954 to 1974.
AB  - This study of a representative community survivor sample of 695 respondents from
      the 1954 Midtown Manhattan Study found that parental socioeconomic status
      unequivocally predicted help-seeking. Age, gender, adult SES, and impaired mental
      health in 1954 predicted help-seeking interactively. The mental health of help
      seekers continued to be unfavorable, or was worsening, from 1954 to 1974.

PMID- 11822218
TI  - Cognitive components of self esteem for individuals with severe mental illness.
AB  - In a sample of 182 individuals with severe mental illness, the applicability of
      reflected appraisals and self-enhancement theories as explanations for global
      self-esteem was examined at two time points on components of stigma, mastery,
      overall functioning, education, and job prestige. Path analysis demonstrated that
      the two theories work independently; and that stigma, mastery, and overall
      functioning are significant, persist over time, and have an enduring effect on
      self-esteem.

PMID- 11822219
TI  - What do mental health professionals really think of family members of mental
      health patients?
AB  - Mental health professionals working at three rural public community mental health
      agencies were asked for their views on the families of mental health patients.
      Findings revealed themes that included families as supportive caregivers, as
      unsupportive agitators, as in pain, as uninformed, and as unequal partners.
      Implications for clinical intervention, education, and research are discussed.

PMID- 11822220
TI  - Parental divorce and young adult children's romantic relationships: resolution of
      the divorce experience.
AB  - Fifty-one romantically involved young Israeli adults, whose parents were
      divorced, were questioned about their romantic relationship, parents' conflict,
      and current feelings about and reconstruction of the divorce. An integrative
      perception of the divorce was found to be related to fewer problems and to higher
      levels of friendship, enjoyment, and intimacy in the relationship. Implications
      for research and intervention with young adults are discussed.

PMID- 11822221
TI  - Characteristics of Pseudomonas aeruginosa isolated from skin infections.
AB  - From January 1995 to June 2000, 19 Pseudomonas aeruginosa were detected in 19
      cases of infectious skin diseases. Coagulase-negative staphylococci coexisted
      with P. aeruginosa in 10 cases and P. aeruginosa was also often associated with
      Enterococcus sp., Staphylococcus aureus, Streptococcus sp. or other species.
      Twelve cases carried P. aeruginosa more predominantly than the other species.
      Some coagulase-negative staphylococci, Enterococcus sp., S. aureus and
      Streptococcus sp. were also predominant. The frequency of predominant P.
      aeruginosa was significantly higher in secondary infections due to ulcers and
      decubitus than in secondary infections due to other skin diseases. P. aeruginosa
      was also often detected in the legs and feet, but not in the trunk. This organism
      showed high sensitivities to antibiotics, except minocycline. No significant
      differences in sensitivity or resistance to antibiotics were found between P.
      aeruginosa when detected as the predominant or single strain and this
      microorganism when detected as the non-predominant strain. Thus, the detection of
      P. aeruginosa important in choosing the appropriate antibiotics to be used and
      this is sometimes influenced by the patient's condition.

PMID- 11822222
TI  - In vitro effect of diamidines on intracellular polyamines of Acanthamoeba
      polyphaga.
AB  - Treatment with the drugs berenil, dibromopropamidine, pentamidine and CGP-4O-215
      were found to alter levels of intracellular polyamines of Acanthamoeba polyphagia
      trophozoites in organisms. While the polyamine, spermidine, consistently remained
      higher in the control organisms incubated at 8, 16 and 32 h respectively, the
      level fluctuated significantly from below 5% to 40% in drug-treated organisms. A
      novel polyamine (polyamine F), yet to be identified, representing 80% of the
      total polyamine extracts and seen in control organisms after 48 h of incubation
      (stationary phase), was seen much earlier in the drug treated organisms.
      Pentamidine, dibromopropamidine and CGP-4O-215 induced the appearance of the
      novel polyamine in the trophozoites after only 8 h of incubation with the drugs
      while induction by berenil occurred after 32 h. It is suggested that diamidine
      drugs either induce encystment or alter the pathway of polyamine metabolism in
      Acanthamoeba. If inducing encystment is the main mode of reaction, then drugs
      that induce early encystment will be less effective in treatment than those that
      delay it.

PMID- 11822223
TI  - Azithromycin and doxycycline in the treatment of female patients with acute
      urethral syndrome caused by Ureaplasma urealyticum: significance of duration of
      clinical symptoms.
AB  - One hundred ninety-two female patients with acute urethral syndrome caused by
      Ureaplasma urealyticum were examined. First, patients were divided into two
      groups: those with clinical symptoms present for less than 3 weeks before the
      start of treatment and those with clinical symptoms 3 weeks or longer before the
      beginning of therapy. The patients were then further divided into groups and
      randomized to receive azithromycin once daily in a single dose of 1 g or 500 mg
      once daily for 6 days, or to receive doxycycline 100 mg b.i.d. for 14 days or 100
      mg b.i.d. for 7 days (eight study groups in all). Clinical and bacteriological
      efficacy were evaluated 3 weeks after the end of therapy. In the group of
      patients with disease symptoms lasting for 3 weeks or longer, eradication and
      clinical cure rates were significantly higher after the administration of
      azithromycin at a dose of 1 x 500 mg/6 days than after a single dose of 1 g (p <
      0.001).

PMID- 11822224
TI  - Protease administration decreases enhanced transforming growth factor-beta 1
      content in isolated glomeruli of diabetic rats.
AB  - Overproduction of transforming growth factor (TGF)-beta 1 messenger RNA is of
      fundamental importance in the pathogenesis of diabetic nephropathy. In vitro
      studies have recently shown that the serine protease trypsin diminishes the
      enhanced TGF-beta 1-expression induced by advanced glycation end products.
      Moreover, proteolytic enzymes may accelerate the removal of TGF-beta 1 from renal
      tissue via a protease-induced activation of alpha 2-macroglobulin (alpha 2M).
      This activation results in the binding of numerous cytokines, including TGF-beta
      1 and is followed by enhanced plasma clearance of the protease alpha 2M-cytokine
      complex. In the present study in streptozotocin-diabetic rats we investigated
      whether the administration of Phlogenzym, a fixed combination of the proteases
      trypsin and bromelain combined with the antioxidant rutosid, modulates renal
      hypertrophy and the formation of TGF-beta 1 in isolated glomeruli. Three weeks
      after induction of diabetes, renal hypertrophy developed with an enhanced
      kidney/body weight ratio. When compared with normal rats, an elevated content of
      intraglomerular TGF-beta 1 (44.25 +/- 21.9 vs. 71.1 +/- 23.4 ng/microgram DNA, p
      < 0.05) as well as fibronectin (2.62 +/- 0.49 vs. 3.42 +/- 0.62 ng/microgram DNA,
      p < 0.05) was observed. In the diabetic rats, treatment with intraperitoneal
      proteases prevented the rise of intraglomerular TGF-beta 1 content (34.9 +/- 22.2
      ng/microgram DNA, p < 0.01) and attenuated the rise of fibronectin (3.03 +/- 1.12
      ng/microgram DNA NS). Furthermore, a decrease in the kidney/body weight ratio (p
      < 0.01) was achieved. Protease administration did not affect blood glucose
      concentration and was without visible adverse effects.

PMID- 11822225
TI  - Pharmacokinetic profile of loprazolam in 12 young and 12 elderly healthy
      volunteers.
AB  - The aim of the study was to investigate the pharmacokinetic profile of acute and
      steady state doses of loprazolam (1 mg) following nighttime administration in 12
      young (18-30 years) and 12 elderly (60-80 years) nonfasting subjects. Loprazolam
      blood plasma concentration was determined by high-performance liquid
      chromatography with ultraviolet absorption detection. The drug was isolated from
      the plasma using a solid phase extraction procedure. On day 1 subjects were
      breathalyzer and given a brief medical examination. Baseline blood samples (10
      ml) were taken via a venous cannula at -1.5 to -0.25 h prior to drug
      administration. Loprazolam was administered at 21.00 and further blood samples
      were taken at 0.5, 1, 1.5, 2.0, 2.5, 3, 4, 5, 6, 8, 10, 12, 18 and 23.5 h
      (baseline sample for day 2). On subsequent days (days 2, 3 and 4) blood samples
      were taken at -0.5 and 2 h. The schedule for day 1 was repeated for day 5 with
      the test period ending at 21.30 on day 6. Significant changes in the
      pharmacokinetics of the drug were evident in the elderly volunteers compared with
      the young volunteers following steady state, where tmax was significantly
      prolonged (CI 90% = 0.80 to 1.25; p < 0.00006) and a decline was observed in peak
      plasma concentration (CI 90% = 0.80 to 1.25; p < 0.00006). However, no
      statistically significant difference was found between the two groups in either
      the elimination half-life of the drug or the area under the curve. Loprazolam
      appears to be well tolerated by both the young and the elderly and only mild
      adverse effects were reported after nighttime administration. These results
      provide valuable data on the pharmacokinetics of the drug in normal clinical
      practice.

PMID- 11822226
TI  - Synthesis and calcium channel antagonist activity of nifedipine analogues
      containing 4(5)-chloro-2-methyl-5(4)-imidazolyl substituent.
AB  - Dihydropyridine having substituted imidazole at 4-position in conjunction with
      various C3, C5 diesters have calcium channel antagonist activity. In this paper a
      group of dialkyl, dicycloalkyl and diaryl ester analogues of nifedipine, in which
      the ortho-nitro phenyl group at position 4 replaced by 2-methyl-4(5)-chloro-5(4)
      imidazolyl substituent, were synthesized and evaluated as calcium channel
      antagonists using the high K+ contraction of guinea-pig ileal longitudinal smooth
      muscle (GPILSM). The results for the symmetrical ester series showed that
      increasing the length chain in C3 and C5 ester substituents increased activity.
      When increasing of the length or lipophilicity accompany with increasing the
      hindrance, the activity decreased. In asymmetrical diester series, the results
      showed when R1 is methyl or ethyl, increasing of the lipophilic property in R
      substituent increases the activity if this high lipophilicity don't accompany
      with steric hindrance. Our results demonstrate that in symmetrical and
      asymmetrical series aromatic compounds were more active than aliphatic compounds.
      In symmetrical diesters compounds, the most active compound was diphenylethyl
      ester derivative, that it was more active than the reference drug nifedipine.
      These structure activity data indicate that the 2-methyl-4(5)chloro-5(4)
      imidazolyl moiety is bioisoester of 2-nitrophenyl and 2-chlorophenyl moieties.

PMID- 11822227
TI  - Synthesis and reactions of some new substituted 6-imidazolyl-4-oxo-4H-1
      benzopyran-3-carboxaldehyde and use of DNA in evaluation of their biological
      activity.
AB  - Vilsmeier-Haack reaction of imidazolyl acetophenone I gave 6-imidazolyl-4-oxo-4H
      1-benzopyran-3-carboxaldehyde II. The compound II was reacted with primary amines
      (1:1 molar ratio) to form the corresponding n-aril (meteroaryl) imino derivatives
      IIIa-f. Treatment of aldehyde II with excess amines (1:2 molar ratio) gave the
      corresponding 2-arylamino-3-arylaminomethylenebenzopyran derivatives IVa-c. The n
      aril (meteroaryl) imino derivatives IIIb,d,e,f were reacted with thioglycollic
      acid to give benzopyranothiazepinone derivatives VIa-d. When the aldehyde II was
      treated with secondary amines gave the corresponding trans-enaminoketones VIIIa
      c. Trans-enaminoketones VIIIa-c were reacted with hydrazines and/or hydroxylamine
      hydrochloride to give pyrazolyl and/or isoxazolyl benzene IXa-c and X,
      respectively. The reaction of aldehyde II with hydrazines on cold gave the
      corresponding hydrazones XIIIa-d. However, the reaction of aldehyde II with
      hydrazines on refluxing gave the corresponding pyrazole derivatives 5 XIVa,b and
      XVa,b.. The structural formula of the new compounds were established by using
      different instrumental analyses. Some compounds in this study were biologically
      evaluated for their ability to bind to DNA.

PMID- 11822228
TI  - Synthesis and antimicrobial activity of some imidazo-[1,2-a]pyridine-2-
      carboxylic acid arylidenehydrazide derivatives.
AB  - Imidazo[1,2-a]pyridine-2-carboxylic acid, ethyl esters were reacted with
      hydrazine hydrate to furnish imidazo[1,2-a]pyridine-2-carboxylic acid hydrazide.
      The hydrazides formed were treated with various aldehydes to obtain 28
      imidazo[1,2-a]pyridine-2-carboxylic acid arylidenehydrazides. Antimicrobial
      activity of the compounds were examined.

PMID- 11822229
TI  - Chemoselective heterocyclization and pharmacological activities of new
      heterocycles--a review. Part V-Synthesis of biocidal 4-thiazolidinones
      derivatives.
AB  - 4-Thiazolidinones have been reported to possess biological activity especially
      fungicidal activity. With an intention to prepare some more 4-thiazolidinones as
      drugs for anti HIV and anticancer activity, we have synthesized some more 4
      thiazolidinones by the action of mercaptoacetic acid on Schiff's base and/or
      heterocyclization of N-substituted thioureas with monochloracetic acid.
      Characterization of 4-thiazolidinone was deduced upon elemental and spectral
      analysis.

PMID- 11822230
TI  - Synthesis and antibacterial activity of some novel N-substituted piperazinyl
      quinolones.
AB  - A series of N-substituted-piperazinyl-quinolones were synthesized and evaluated
      for in vitro antibacterial activity. Compounds with a 2-(2,4-dichlorophenyl)-2
      oxoethyl group attached to the piperazine ring (5a-c) had similar antibacterial
      activity to the reference drugs, ciprofloxacin, norfloxacin and enoxacin against
      both Gram-positive and Gram-negative bacteria. The oximes 6a-c and 6g-i were
      almost less active than corresponding ketones against the tested microorganisms,
      however the 2,4-difluorophenyl analogues (6g-i) were more active than 2,4
      dichlorophenyl derivatives (6a-c). If the hydrogen of oxime is replaced with a
      benzyl group (6d-f & 6j-l), in-vitro antibacterial activity was decreased against
      both Gram-positive and Gram-negative bacteria. Generally ciprofloxacin
      derivatives were more active than norfloxacin and enoxacin derivatives.

PMID- 11822231
TI  - Synthesis of some 4-(alkylidene/arylidene)amino-2,4-dihydro-5- (2-thienyl)-3H
      1,2,4-triazole-3-thiones tested for antimicrobial activity.
AB  - A series of 4-(alkylidene/arylidene)amino-2,4-dihydro-5- (2-thienyl)-3H-1,2,4
      triazole-3-thiones (2a-h) were synthesized. The structural elucidation of all the
      compounds was made on the basis of analytical and spectral data (IR, 1H-NMR and
      EIMS). All synthesized compounds were evaluated for in vitro antimicrobial
      activity against various bacteria and fungi. Some of the compounds demonstrated
      antimicrobial activity against Staphylococcus aureus ATCC 6538, Staphylococcus
      epidermidis ATCC 12228, Trichophyton rubrum, Trichophyton mentagrophytes var.
      erinacei NCPF-375 and Microsporum canis (MIC 50-6.25 mg/ml). The in vitro
      antimycobacterial activity of the new compounds was also investigated. Some of
      the compounds showed varying degrees of inhibition (2-40%) against Mycobacterium
      tuberculosis H37Rv in the primary screen that was conducted at 12.5 mg/ml using
      the BACTEC 460 radiometric system.

PMID- 11822232
TI  - Synthesis of some new triazoles as potential antifungal agents.
AB  - The rise in the incidence of fungal infections over the past two decades,
      particularly those caused by opportunistic pathogens in immune-compromised
      patients, has strengthened the need for new antifungal drugs. New triazole
      derivatives were synthesized and evaluated for their in-vitro antifungal
      activities against three species of fungi. Most of the prepared compounds showed
      good antifungal activity. Three compounds exhibited pronounced activity against
      Cryptococcus neoformans with MIC less than 12.5 g/ml.

PMID- 11822233
TI  - Synthesis and biological studies of some imidazolinone derivatives.
AB  - A Series of 4-(1-Aryl-5-oxo-2-phenyl-2-imidazolin-4-yl) metheno-5-chloro-3-methyl
      1-phenyl-3-pyrazole) were synthesised and tested for their antibacterial,
      antiinflammatory and analagesic activities. Some of the compounds showed
      significant antiinflammatory properties.

PMID- 11822234
TI  - Computerized calculation of biological potency: presentation of the interactive
      computer program "POTENCY" (assays: "2 + 2" doses, "3 + 3" doses, "twin cross
      over assay" and "probit analysis" ("2 + 2" doses).
AB  - Paper presents the interactive computer program "POTENCY" written in BASIC
      program language, based on the algorithm for classifying biological assays using
      the assays: "2 + 2" doses, "3 + 3" doses, twin cross-over assay and probit
      analysis ("2 + 2" doses) described in Yugoslav Pharmacopeia (Ph. Jug. IV). The
      program execution is presented by assay examples of biological potency
      calculation described in European Pharmacopeia (Eur. Ph. 1997). The assay
      examples have simultaneously been the measure of program execution correctness.

PMID- 11822235
TI  - [Filter sterilization and penetration battery].
AB  - Currently sterilising filtration is one of the most commonly used techniques in
      the Pharmaceutical Industry. Some doubts and misunderstandings can, however,
      arise from certain aspects of this consolidated and well-known technology. Some
      examples? Does speaking about 0.2 or 0.22 um necessarily mean a sterilising
      filter? What are 0.1 um filters? How well do we understand the phenomenon of
      bacterial penetration in sterilising filters?

PMID- 11822236
TI  - [Assessing the chemical cross-reaction from cefixime and some nonsteroidal anti
      inflammatory agents in a soluble formulation].
AB  - The presence of chemical cross-reactivity between drugs may be an underestimated
      factor, responsible for decreased bio-availability of a drug active component(s);
      the absence of chemical cross-reactivity between drugs is undoubtedly the
      prerequisite for their simultaneous co-administration. Here, by means of thin
      layer chromatography, we show that cefixime, a third generation oral
      cephalosporin, does not display chemical reactivity versus a series of non
      steroidal antiinflammatory agents. The four compounds tested can therefore be
      safely soluted together with the cephalosporin.

PMID- 11822237
TI  - An improved HPLC-fluorescence stereoselective method for analysis of (+)-S- and (
      )-R-sotalol enantiomers in plasma sample.
AB  - A simplified high performance chromatographic method (HPLC) was performed for
      sotalol enantiomers in plasma samples for purposes of investigation of the
      kinetic disposition of racemic sotalol in cardiac arrhythmic patients under
      multiple dose and multidrug therapy regimens. After addition of NaCl:Na2CO3 (4:1)
      and plasma protein precipitation by acetonitrile:methanol mixture (1:1) the
      supernatant was evaporated. The residue containing sotalol racemate was submitted
      to derivatization reaction with (-)-menthylcloroformate to R(-)- and S(+)-sotalol
      diastereoisomers. The diastereoisomers were resolved in HPLC, by a C18 column
      with fluorescent detection under lexcitation = 235 nm and lemission = 310 nm. The
      retention times for R- and S-sotalol were 20 and 22 minutes while that of
      internal standard S(-)-atenolol, was 17 minutes. The detection limit for each
      enantiomer was 12.5 ng/mL and intra-day/inter-day coefficients of variation were
      less than 10% for each enantiomer within a concentration range of 200 and 2000
      ng/mL. The method was appropriate for the objective proposed.

PMID- 11822238
TI  - Assay of oxazepam in human plasma by reversed-phase high-performance liquid
      chromatography.
AB  - A rapid, selective and sensitive method for determination of oxazepam in plasma
      is described, based on reversed-phase high-performance liquid chromatography. The
      separation was performed on an analytical 300 x 3.9 mm i.d m-bondapack C18 column
      using UV detector at 230 nm. A mixture of methanol-phosphate buffer (50:50 v/v)
      adjusted to pH 6 at a flow rate of 1.5 mL min-1 was used as mobile phase. The
      proteins were precipitated with a 24% perchloric acid (HClO4) solution and
      analytical recovery was complete. Diazepam was used as an internal standard. The
      standard curve was linear over the range 100-1600 ng mL-1 and the detection limit
      for oxazepam was 30 ngmL-1. The inter- and intra-assay coefficients of variation
      were found to be less than 10%. This method is simple, rapid and sensitive enough
      for monitoring of oxazepam levels in clinical studies and pharmacokinetic
      aspects.

PMID- 11822239
TI  - Determination of amitriptyline in plasma samples by high-performance liquid
      chromatography.
AB  - A simple and selective high-performance liquid chromatographic method for the
      determination of amitriptyline in human plasma has been developed. For plasma
      samples, the protein was removed with 1 M NaOH and 0.7 M ZnSO4. aqueous
      solutions. The chromatographic separation was performed on an analytical
      mbondapak C18 column (250 3.9 mm, i.d) with an isocratic mobile phase consisting
      of phosphate buffer-acetonitrile-triethylamine (65:35:0.1 v/v/v) adjusted to pH
      5.1. Clomipramine was used as an internal standard. Using ultraviolet detection
      at 239 nm, the detection limit for amitriptyline in plasma was 5 ng/ml. No
      interferences were found with tricyclic antidepressant drugs, which allows this
      method to be used in clinical studies. The calibration curve was linear over the
      concentration range 5-200 ng/ml. The recovery was complete for plasma. The inter
      day and intra-day assay coefficients of variation were found to be less than 10%.

PMID- 11822241
TI  - In vitro dissolution test of tamoxifen citrate preparations.
AB  - The Tamoxifen Citrate is available in oral tablet and is highly used as an
      endocrines therapy for breast cancer. Products from assorted makers
      bioavailability problems has been associated to the incomplete dissolution of the
      tablets. We determined the dissolution in vitro of five pharmaceutical
      preparations of the Tamoxifen Citrate available in the Brazilian market,
      Novaldex, Tecnotax, Zita, Tamoxifen (TEVA) and Tamoxifeno (PHARMACIA) all
      containing 10 mg of active drug. The methodology was conducted according to the
      in vitro dissolution test from USP XXIII. Other test such as mass uniformity,
      content uniformity and hardness were accomplished seeking to relate physical
      characteristics with the in vitro dissolution of these preparations. All the
      formulations presented liberation more than 75% of the active drug in 30 minutes.
      Any relationship was not observed between the in vitro dissolution, the average
      weight, the mass uniformity and the hardness of the tablets whereas the
      liberation was proportional to the tamoxifen citrate content. Although one of the
      tested products did present a higher dissolution profiles in comparison to the
      other tested preparation.

PMID- 11822240
TI  - Development and evaluation of matrix and two layered sustained release
      suppositories of theophylline.
AB  - Theophylline loaded conventional suppositories, sustained release matrix
      suppositories and sustained release two layered suppositories were prepared using
      polyethylene glycol 4000 and eudragit RS-100 and their characteristics were
      evaluated both in-vitro and in-vivo. In comparison to conventional suppositories,
      the release of the drug from sustained release matrix suppositories was gradual
      and extended over a period of time. On the other hand two layered suppositories
      produced an initial quick release followed by extended release of the drug. The
      in-vivo results were found to correlate with the in-vitro results.

PMID- 11822242
TI  - Tensile bond strength of a polymeric intra-buccal bioadhesive: the mucin role.
AB  - The intra-bucal polymeric bioadhesive systems that can stay adhered to the oral
      soft tissues for drug programmed release, with the preventive and/or therapeutic
      purpose have been employed for large clinical situations. A system based on
      hydroxypropyl methyl cellulose/Carbopol 934TM/magnesium stearate (HPMC/Cp/StMg),
      was developed with the sodium fluoride as an active principle. This kind of
      system was evaluated according to its resistance to the removal by means of
      physical test of tensile strength. Swine buccal mucosa extracted immediately
      after animals' sacrifice was employed as a substrate for the physical trials to
      obtain 16 test bodies. Artificial saliva with or without mucin was used to
      involve the substrate/bioadhesive system sets during the trials. Artificial
      salivas viscosity were determined by means of Brookfield viscometer, and they
      showed 10.0 cP artificial saliva with mucin, and 7.5 cP artificial saliva without
      mucin. The tensile strength assays showed the following averages: 12.89 Pa for
      the group "artificial saliva with mucin", and 12.35 Pa for the group "without
      mucin". Statistical analysis showed no significant difference between the assays
      for both artificial salivas, and we can conclude that the variable mucin did not
      interfere with the bioadhesion process for the polymeric devices.

PMID- 11822243
TI  - Raising care levels, lowering costs: can a hospitalist program help?

PMID- 11822244
TI  - Employing practices used by centers of excellence.

PMID- 11822245
TI  - What should your formulary look like?

PMID- 11822246
TI  - Is your culture e-compatible?

PMID- 11822247
TI  - Transitioning the mentoring relationship.

PMID- 11822248
TI  - Community health: strategy or slogan?

PMID- 11822249
TI  - The controversial new OPPS rule.

PMID- 11822250
TI  - Working differently. The IOM's call to action.

PMID- 11822251
TI  - Making the most of assessment feedback.

PMID- 11822252
TI  - Improving quality through committee structure.

PMID- 11822253
TI  - A community approach to free care.

PMID- 11822254
TI  - The value of volunteers.

PMID- 11822255
TI  - The future role of the hospital.

PMID- 11822256
TI  - Identifying barriers to the use of research faced by public health physicians in
      Norway and developing an intervention to reduce them.
AB  - OBJECTIVES: To explore why public health physicians seldom use research-based
      information and to develop an intervention to remedy this on the basis of this
      study, other research literature and suitable theories of information-seeking and
      professional behaviour change. METHODS: A qualitative study was conducted using
      focus groups, observation of individuals and interviews. The setting was
      Norwegian public health practice; 52 public health physicians from all over
      Norway participated in the study. RESULTS: We identified several barriers to the
      use of scientific literature that could be categorised as: psychological
      variables; environmental variables; and source characteristics. We developed an
      intervention that attempts to address these barriers, informed by previous
      research on the effectiveness of interventions to change professional practice
      and incorporating elements from social cognitive theories and the theory of
      innovation diffusion. CONCLUSIONS: The Norweigian public health physician works
      in an isolated environment which does not facilitate searching or obtaining
      scientific information, which does not ask for this information and far less
      encourages its use as a basis for decision-making. An intervention tailored to
      reduce some of the barriers to research use may lead to more frequent and
      extensive use of such information in public health decision-making.

PMID- 11822257
TI  - Does waiting for total hip replacement matter? Prospective cohort study.
AB  - OBJECTIVES: To assess the impact on the outcome of total hip replacement of the
      length of timing spent waiting for surgery. METHODS: One hundred and forty-three
      orthopaedic and general hospitals provided information about aspects of surgical
      practice for each total hip replacement conducted between September 1996 and
      October 1997 for publicly and privately funded operations in five English health
      regions. These data were linked to patient information about hip-related pain and
      disability status (measured using the Oxford Hip Score) before operation and at 3
      and 12 months after. Data were analysed using multiple regression analysis.
      RESULTS: Questionnaires were completed by surgeons for 10,410 (78%) patients
      treated during the recruitment period and by 7151 (54%) patients. Twelve months
      after total hip replacement, the majority of patients experienced substantial
      improvements in hip-related pain and disability (as measured by the Oxford Hip
      Score). Those patients who started with a worse Oxford Hip Score before the
      operation tended to remain worse after the operation. Worse pre-operative score
      was associated with an increased length of either outpatient or inpatient wait,
      and this trend remained after the operation. The relationship between waiting
      time and outcome remained after adjustment for possible confounding variables. A
      consistently worse score was observed in public compared with private patients at
      all three time-points. In addition, in both sectors, those patients who were
      socially disadvantaged had a worse score than more socially advantaged patients
      both before and after the operation. CONCLUSIONS: Waiting for surgery is
      associated with worse outcomes 12 months later. Longer-term outcome needs to be
      considered to see if this association persists.

PMID- 11822259
TI  - Developing a model to enhance the capacity of statutory organisations to engage
      with lay communities.
AB  - OBJECTIVE: To understand the processes that constrain the capacity of statutory
      organisations to work effectively with lay communities and to develop a model to
      enhance their capacity to do so. METHODS: The research consisted of three
      elements: a review of relevant literature; in-depth interviews with a purposive
      sample of people who had recently been involved in community-statutory sector
      partnership; and a deliberative workshop involving ten expert witnesses, selected
      to reflect a range of sectors and levels within organisations. RESULTS: Many
      factors contribute to a lack of effective strategic partnerships between lay
      communities and statutory organisations. These factors fall into five domains:
      the community's capacity to engage; the skills and competencies of organisational
      staff; the dominant professional service culture; the overall organisational
      ethos and culture; and the dynamics of the local and national political systems.
      A model of the relationships and/or interaction between these domains is
      postulated. There is potential for testing this model with statutory
      organisations to see whether it concurs with their reality and whether it is
      enhancing their organisational capacity. CONCLUSIONS: Commonly occurring
      constraints to effective partnerships between statutory organisations and lay
      communities need to be identified and addressed by applying a dynamic model of
      the type presented here.

PMID- 11822258
TI  - Salaried contracts in UK general practice: a study of job satisfaction and
      stress.
AB  - OBJECTIVES: To compare job satisfaction and stress levels of general
      practitioners (GPs) employed on salaried contracts with GPs on a 'standard'
      performance-related contract paid by fee-for-service and capitation. METHODS: Job
      satisfaction and stress levels were assessed using data from two postal surveys
      of GPs: a national survey of 'standard' contract GPs carried out in 1998; and a
      survey of salaried GPs and their non-salaried GP employers in 1999. Differences
      in satisfaction and stress scores were assessed by t-tests; regression analysis
      was used to control for confounding factors and possible selection bias. RESULTS:
      We achieved a response rate of 77% in the 1999 survey of salaried and non
      salaried GPs; 48% of 'standard' contract GPs responded in the 1998 survey. We
      found that salaried GPs were as satisfied overall as both non-salaried GP
      employers and GPs on the 'standard' contract, even after controlling for
      confounding factors and selection bias. Salaried GPs were more satisfied with
      their remuneration, working hours and the recognition they got for their work.
      They experienced more stress with two factors but less stress with 19 factors
      compared with the 'standard' contract GPs. CONCLUSIONS: Overall job satisfaction
      levels among salaried doctors were similar to those of doctors on contracts paid
      by mixed fee-for-service and capitation. Future studies of job satisfaction
      levels under different doctor payment systems need to take account of the extent
      to which doctors have preferences for different types of contract if they are to
      derive unbiased results.

PMID- 11822260
TI  - When research knowledge is unwelcome: studying the health effects of in vitro
      fertilization.
AB  - OBJECTIVES: To illustrate the complexity of setting up evaluative research when
      it is perceived to threaten professional and financial interests. METHODS: A case
      study based on participatory observation of attempts to study the delivery and
      health consequences of in vitro fertilization (IVF). Two research projects were
      observed: one used well-baby clinic records and this project was completed; the
      other project aimed to use national data and record linkage to study the patterns
      of use of IVF, the IVF success rate, and the health effects on women and on
      children. This project could not be carried out as planned. The reasons for this
      were studied. Observations, documents and notes on discussions were analysed.
      RESULTS: IVF clinicians were not interested in the second project until faced
      with a concrete request to provide data. Tactics to avoid providing data included
      asking for more information on the project, transferring the request from one
      person to another, and arguing against the project. The arguments used and
      conditions set by different clinics were similar and centred around data
      confidentiality and authorship of the anticipated research reports. This case
      illustrated features that occur when health care is evaluated by non-clinicians:
      quarrels over mandate and ownership; and conflicts between the different research
      traditions of clinicians and epidemiologists. CONCLUSIONS: To facilitate
      evaluation by outsiders, new norms are needed and outside researchers need
      institutional back-up. Outside evaluation may need a determined push from health
      care funders and a cultural change within the clinical community itself.

PMID- 11822261
TI  - Organization and financing of British primary care groups and trusts:
      observations through the prism of US managed care.
AB  - There are many parallels between the UK's new primary care commissioning
      organizations and the managed care organizations and integrated delivery systems
      that have evolved in the USA over the last three decades. Those building primary
      care groups and trusts (PCG/Ts) can learn from the American experience with
      health maintenance organizations and other similar entities. These lessons should
      also be relevant to those in other countries interested in establishing
      innovative primary care led organizations within the broader structure of a
      socialized health care system. Following an overview of US managed care and an
      update of the progress of the UK's PCG/Ts, we go on to suggest how new consortia
      of PCG/Ts might be developed and how budgets and provider incentives could be
      structured. This international comparison suggests that the resources needed to
      support the development of effective PCG/Ts will be considerable, as will the
      need to maintain organizational flexibility. If primary care organizations are to
      thrive, it will be essential to develop truly integrated budgets for primary and
      secondary care.

PMID- 11822262
TI  - Statistical heterogeneity in systematic reviews of clinical trials: a critical
      appraisal of guidelines and practice.
AB  - OBJECTIVE: Heterogeneity between study results can be a problem in any systematic
      review or meta-analysis of clinical trials. Identifying its presence,
      investigating its cause and correctly accounting for it in analyses all involve
      difficult decisions for the researcher. Our objectives were: to collate
      recommendations on the subject of dealing with heterogeneity in systematic
      reviews of clinical trials; to investigate current practice in addressing
      heterogeneity in Cochrane reviews; and to compare current practice with
      recommendations. METHODS: We review guidelines for those undertaking systematic
      reviews and examine how heterogeneity is addressed in practice in a sample of
      systematic reviews, and their protocols, from the Cochrane Database of Systematic
      Reviews. RESULTS: Advice to reviewers is on the whole consistent and sensible.
      However, examination of a sample of Cochrane protocols and reviews demonstrates
      that the advice is difficult to follow given the small numbers of studies
      identified in many systematic reviews, the difficulty of pre-specifying important
      effect modifiers for subgroup analysis or meta-regression and the unresolved
      debate concerning fixed versus random effects meta-analyses. There was
      disagreement between protocols and reviews, often either regarding choice of
      important potential effect modifiers or due to the review identifying too few
      studies to perform planned analyses. CONCLUSION: Guidelines that address
      practical issues are required to reduce the risk of spurious findings from
      investigations of heterogeneity. This may involve discouraging statistical
      investigations such as subgroup analyses and meta-regression, rather than simply
      adopting a cautious approach to their interpretation, unless a large number of
      studies is available. The notion of a priori specification of potential effect
      modifiers for a retrospective review of studies is ill-defined, and the
      appropriateness of using a statistical test for heterogeneity to decide between
      analysis strategies is suspect.

PMID- 11822263
TI  - Bias measuring bias.
AB  - The British National Health Service and other publicly funded health systems
      operate on the principle that health care should be provided solely on the basis
      of need. Yet the literature abounds with reports of bias in health care use. In
      order to defend such a charge, two conditions must be met. The first condition is
      that treatment decisions must be shown to be unfair in that they are not made
      solely on the basis of need. This paper demonstrates the importance of
      considering the fair distribution of health care from two, related, perspectives.
      The first is that people with equal needs should be treated the same (equal use
      for equal need). This is referred to as the achievement of horizontal equity. The
      alternative perspective is that people with greater needs should have more
      treatment than those with lesser needs (unequal use for unequal need). This is
      referred to as the achievement of vertical equity. Although these perspectives
      are logically linked, demonstration of equal use for equal need does not
      necessarily indicate unequal use for unequal need. This is because it cannot be
      assumed that equal use occurs at every level of need. The second condition that
      must be met is that clinical judgement must be shown to be influenced by
      prejudicial notions about patients. Such research is fraught with methodological
      difficulties, and the charge of biased clinical decision-making is usually made
      as a result of a process of exclusion. Methods that could be used to examine the
      extent to which inequalities in health care use are due to bias are described.

PMID- 11822264
TI  - Performing laboratory compliance audits.
AB  - Billions of dollars are paid improperly each year because of laboratory service
      billing errors that include services not covered, incorrect coding, lack of
      medical necessity, and unsupported services. An important part of a laboratory
      compliance program is the compliance audit. This article discusses barriers to a
      successful audit, audit skills for the laboratory, areas to cover in an audit,
      and writing the audit report. Intermountain Health Care (IHC) is an integrated
      health-care system consisting of 20 hospitals in Utah and Idaho, health plans
      with 450,000 directly covered lives and contracts to third-party insurance
      companies covering 500,000 additional lives, and 75 other facilities with 400
      employed physicians. Approximately 1,000 of IHC's 23,000 employees work in
      laboratories.

PMID- 11822265
TI  - Medicare coverage of new clinical diagnostic laboratory tests: the need for
      coding and payment reforms.

PMID- 11822266
TI  - Practical lessons in laboratory planning.

PMID- 11822267
TI  - Emotions at work.
AB  - Health-care organizations are just beginning to recognize the importance of
      developing a manager's emotional quotient, or interpersonal skills.

PMID- 11822268
TI  - What does all of this leadership stuff mean to me?

PMID- 11822269
TI  - A unique approach for reducing specimen labeling errors: combining marketing
      techniques with performance improvement.
AB  - Challenged with persistent specimen labeling errors that were resistant to
      improvement efforts, our organization selected "reducing specimen labeling
      errors" as an indicator for a hospital-wide error reduction goal. Modeling
      quality improvement guidelines published in the institute of Medicine's report
      "To Err is Human, Building a Safer Health System," a multidisciplinary task force
      "error proofed" processes. The task force created new standards and crafted an
      implementation plan using an internal marketing strategy to change current
      practices and reinforce patient safety as a core value within our institution.
      This unique approach reduced errors by 41% and provided learning opportunities
      that will be valuable in more challenging patient safety initiatives such as
      medication error reduction.

PMID- 11822270
TI  - Finding a job after 50.

PMID- 11822271
TI  - Celebrities and confidentiality.

PMID- 11822272
TI  - Common cent$ 3: Free trade and the true cost of lost opportunities.

PMID- 11822273
TI  - Retaining managers: the power of the (extra) day off.

PMID- 11822274
TI  - The secrets to successful change.

PMID- 11822275
TI  - Should non-phlebotomists be allowed to draw blood?

PMID- 11822276
TI  - Critical access hospital standards approved.

PMID- 11822277
TI  - A follow-up review of wrong site surgery.

PMID- 11822278
TI  - Emergency management standards clarified.

PMID- 11822279
TI  - [Study on variation and interrelations of characteristics at ginseng germplasms].
AB  - The variation and interrelations of some characteristics of Panax ginseng
      germplasms(lines), which were five selfmating generations of some single plants
      were studied. Methods of multivariate analysis, such as correlation, regression,
      or clustering, and coefficient of variation were used. The results were of
      benefit to the breeding and standardized planting of Panax ginseng.

PMID- 11822280
TI  - [Observation on biological characteristics of Hedyotis diffusa].
AB  - The present work enunciats the phenophase and plant organ development of Hedyotis
      diffusa Willd, at Nanjing region. These results can give a reference for the
      plant growing practice.

PMID- 11822281
TI  - [Comparison with the content of total alkaloid of Dendrobium nobile in different
      growing conditions].
AB  - This article reported the contents of total alkaloid from Dendrobium nobile
      Lindel, in different growing conditions. The result showed that the total
      alkaloid contents from plants taming on sawdust media were higher than from
      growing on trees at wild. The experiment also found total alkaloid contents of
      leaves were higher than that of stems.

PMID- 11822282
TI  - [Studies on DNA amplification fingerprinting of cortex Magnoliae officinalis].
AB  - Total genomic DNA samples of Chinese traditional medicine(CTM) Cortex Magnoliae
      Officinalis ("Houpo"), its counterfeits and substitutes were amplified by DNA
      amplification fingerprinting(DAF). Their amplified DNA banding patterns were
      distinguished on PAGE. The results show that DAF can be used to identify CTM
      "Houpo", its counterfeits and substitutes, which is also quite valuable for
      correctly introducing original plant.

PMID- 11822283
TI  - [The status quo survey of false and inferior species in Chinese medicinal
      materials market in Hubei Province].
AB  - By taking a sample, unqualified varieties were investigated found in Chinese
      medicinal material examinatorial work near twenty years of six regional level and
      three countrylish level institutes for drug control and one comprehensive level
      three grade-A hospital. By mail, false and inferior species and their origin of
      Chinese medicinal material were investigated found by sixteen institutes for drug
      control near ten years in Hubei province. 539 kinds of adulterants (750 cases)
      including 24 toxic species were found in above-mentioned investigations. Fales
      and inferior species are rampant in minority regions, which threatens people's
      health severely. It is urgent for supervising department to gorem the condition
      strictly.

PMID- 11822284
TI  - [Descriptions and microscopic identification of Argyreia acuta Lour].
AB  - OBJECTIVE: To provide evidences for the identification of Argyreia acuta Lour.
      METHOD: By descriptions and microscopic identification. RESULT: The characters
      including stomata covered by many glandular hairs in dorsal surface of leaf of
      Argyreia acuta were obvious. CONCLUSION: The result provided evidences for the
      identification of Argyreia acuta Lour.

PMID- 11822285
TI  - [Microscopic and UV identification of Millettia pulchra Kurz var. Laxior(Dunn) Z.
      Wei].
AB  - OBJECTIVE: To provide evidences for the identification of Millettia pulchra Kurz
      var. Laxior (Dunn) Z. Wei. METHOD: Microscopic and UV identification. RESULT:
      Obvious identificational character was found, fox example, there are stone cell
      groups and fiber bundles arranging with ring uncontinously in cortex; there are
      fibers containing square crystals in the powder; the EtOH solution of the powder
      has absorbing peaks in 261, 216, 204 +/- 1 nm wave length, and the CHCl3 solution
      262 +/- 1 nm wave length. CONCLUSION: The character provided evidences for the
      identification of Millettia pulchra Kurz var. Laxior(Dunn) Z. Wei.

PMID- 11822286
TI  - [Effect of Rheum palmatum decoction on increasing intelligence].
AB  - OBJECTIVE: To observe the nootropic effect of Rheum palmatum decoction in mice.
      METHOD: Step-down test. RESULTS: Rheum palmatum decoction could increase learning
      and memory ability of old mice and also improve the impairments of memory
      acquisition, memory consolidation and memory retrieval induced by scopalamine,
      NaNO2 and 40% EtOH respectively in mice. CONCLUSION: Rheum palmatum decoction
      contains the substances of increasing intelligence which may be substantial basis
      of the decoctions mainly containing Rheum palmatum theraping aphasia from
      apoplexy, senile dysmnesis, sequel from brain trauma, etc.

PMID- 11822287
TI  - [Pharmacokinetical study of safflor yellow on rat acute model of blood stasis
      syndrome].
AB  - OBJECTIVE: To study the pharmacokinetical character of safflor yellow in rat
      acute model of blood stasis syndrome. METHODS: The rat acute model of blood
      stasis syndrome was made by i.p. adrenalin (0.07 ml/kg) and the stimulation of
      ice-water. At the time of 5, 10, 30, 60, 120, 180, 320, 480 min, the
      concentration of safflor yellow in the serum after i.v. safflor yellow (37.08
      ml/kg) was determined. RESULTS: The concentration-time date of safflor yellow in
      rat acute model of blood stasis syndrome was shown to fit a double-compartment
      open model, t1/2 alpha = 1.43 min, t1/2 beta = 95.65 min, AUC = 49,632.90
      micrograms.min/ml; while the concentration-time data of safflor yellow in normal
      rat was shown to fit a single-compartment open model, t1/2 alpha = 66.27 min, AUC
      = 42,267 micrograms.min/ml. CONCLUSION: The metabolism of safflor yellow was
      evidently later in rat acute model of blood stasis syndrome than in normal rat.

PMID- 11822288
TI  - [Determination of ferulic acid absorbed into human serum from oral decoction of
      rhizoma chuanxiong and pharmacokinetic study of ferulic acid].
AB  - OBJECTIVE: To improve the HPLC method for determining ferulic acid(FA) in the
      human serum and to research FA clinical pharmacokinetics. METHOD: Serum
      concentrations of FA were determined by HPLC using methanol-water-acetic acid
      (40:59.7:0.3, v/v) as the mobile phase and the column packed with ODS (150 mm x
      4.6 mm, 5 microns) as a fixed phase and the flow rate was 1.0 ml/min. FA was
      detected at 320 nm wave length. The internal standard was coumarin. The serum
      samples were treated by the water-boiling method. Peak of FA in serum was
      recognized by photodiode-array detection. RESULT: FA and internal standard were
      separated completely under the condition described as above. FA was linear in the
      range of (40.16-8032 ng/ml) (r = 0.9975). The CV was less than 10%, the average
      recovery was 100.3%, and the limit concentration in serum was 25.1 ng/ml. PK was
      in accordance with open bicameral model. CONCLUSION: This method can be applied
      to clinical pharmacokinetic study of FA.

PMID- 11822289
TI  - [Pharmacological study on the extracts from Typhonium flagelliforme Blume].
AB  - OBJECTIVE: To study the pharmacological action of Typhonium flagelliforme
      Blune(TFB). METHODS: Relieving a cough and eliminating expectoration were
      observed by strong aqua spray and pheol red determining methods. The
      antiasthmatic action was observed by whole spraying method. The analgesia and
      anti-inflammation were studied by the twisting test induced by acetic acid and
      ear swelling induced by xylene. The sedation was determined by autonomic action
      test. The toxicity of TFB was studied through the acute toxicity test in mice.
      RESULTS: All the water, alcohol and ester extracts of TFB could significantly
      decrease cough times, increase phenol red outage in trachea, prolong asthma
      incubation period, decrease twisting times, inhibit ear swelling and decrease
      autonomic action times. CONCLUSION: All water, alcohol and ester extracts of TFB
      have effects of relieving a cough, eliminating expectoration, antiasthmatic,
      analgesia, anti-inflammation and sedation. The maximum tolerances of TFB for
      acute toxicity were 720 g/kg(water extract), 900 g/kg (alcohol extract) 3240
      g/kg(ester extract) respectively.

PMID- 11822290
TI  - [Study on the protective effect of xinkang oral liquid on the isoproterenol
      induced ischemic myocardial damage in rats].
AB  - OBJECTIVE: To study the protective effect of Xinkang oral liquid on the ischemic
      myocardial damage. METHODS: Ischemic myocardial damage model was obtained by i.p.
      85 mg/kg isoproterenol. The level of superoxide dismutase (SOD), malondialdehyde
      (MDA), creatine kinase (CK), lactic dehydrogenase (LDH) in the serum and
      endothelin (ET) in the plasma were detected. RESULTS: The level of ET, MDA, CK,
      LDH of Xinkang oral liquid group was much lower than that of model group (P <
      0.01). The SOD activity was higher than that of model group (P < 0.01). The level
      of Xinkang oral liquid group was lower than that of Shuxin oral liquid group. The
      SOD activity of Xinkang oral liquid group was much higher than that of Shuxin
      oral liquid group (P < 0.01). CONCLUSION: Xinkang oral liquid can prevent the
      myocardium from ischemic damage.

PMID- 11822292
TI  - [Discussion of leigong 17 processing methods].
AB  - "Seventeen Methods" plays an important role in the field of processing medicinal
      herbs, and also makes a notable impact on modern ages. However, some problems
      among it are still existed. According to the origin of "17 Methods" and
      interrelating records, a simple description about its objections was given.

PMID- 11822291
TI  - [Determination of triacontanol and octacosanol in fenglasu and fenglasu capsules
      by capillary gas chromatography].
AB  - OBJECTIVE: The method was established for the determination of triacontanol and
      octacosanol in fenglasu and fenglasu capsules. METHODS: The solvent was
      chloroform. The internal standard was hexatriacontanol. Using SIMPLCITY-1
      capillary column, flame ionization detector was specified, injector temperature
      was 300 degrees C, and the column temperature rise by programming. [Initial
      temperature was 240 degrees C, maintaining 1 min and then rising the temperature
      (5 degrees C.min-1) to 300 degrees C for 15 min]. The flow rate of Nitrogen was
      27 ml.min-1. RESULTS: The calibration curves were linear in the range of 0.4-1.6
      mg/ml for triacontanol(r = 0.999), 0.2-0.6 mg/ml for octacosanol(r = 0.9996)
      respectively. The average recovery (n = 9) was 99.2% for triacontanol (RSD =
      1.15%), 99.91% for octacosanol (RSD = 1.40%). CONCLUSION: The method is rapid,
      accurate and reliable for the quality control of fenglasu and fenglasu capsules.

PMID- 11822293
TI  - Is there a golden ratio?

PMID- 11822294
TI  - Relapse and the need for permanent fixed retention.

PMID- 11822295
TI  - Permanent fixed lingual retention.

PMID- 11822296
TI  - 2001 JCO Orthodontic Practice Study. Part 3 practice growth and other
      comparisons.

PMID- 11822297
TI  - Three perspectives on successful practice transition. Interview by Howard D. Iba.

PMID- 11822298
TI  - The hostess concept: the ultimate practice builder.

PMID- 11822299
TI  - An unusual ankylosis in an orthodontic case.

PMID- 11822301
TI  - Proceedings of the Serono Symposium on Embryos, Embryonic Stem Cells and
      Transplantation. 27 April 2000. Canberra, Australia.

PMID- 11822300
TI  - A nickel titanium space regainer-retainer.

PMID- 11822302
TI  - School Health Policies and Programs Study (SHPPS) 2000: a summary report.

PMID- 11822303
TI  - [International Symposium "Biology of Cells in Culture". St. Petersburg, Russia,
      October 16-18, 2001. Abstracts].

PMID- 11822304
TI  - The most cited books in analytical chemistry.

PMID- 11822305
TI  - A guide to the UK Adult Dental Health Survey 1998.

PMID- 11822306
TI  - [Allergic dermatitis caused by epoxy resins and evaluation of capacity related to
      the specific task. Clinical cases].

PMID- 11822307
TI  - [What capacity evaluation for naval carpenter applicants with lumbosacral
      abnormalities detected radiographically?].

PMID- 11822308
TI  - [Tests of auditory fatigue and their possible use in the prevention of
      occupational hypoacusia: apropos of a clinical case].

PMID- 11822309
TI  - [Are always justified limitations of capacity in solderers with moderate
      deficiency of respiratory function?].

PMID- 11822312
TI  - Proceedings and abstracts of the 28th annual conference of the International
      Embryo Transfer Society (IETS). Foz do Iguassu, Parana, Brazil. January 12-15,
      2001.

PMID- 11822310
TI  - [Assessment of capacity with permanent limitation of employees in a hospital
      enterprise in North Italy].

PMID- 11822313
TI  - French Consensus Conference on Acute Pancreatitis: Conclusions and
      Recommendations. Paris, France, 25-26 January 2001.

PMID- 11822314
TI  - One of the most interesting pro-apoptotic proteins recently identified is the TNF
      related apoptosis-inducing ligand (TRAIL).

PMID- 11822315
TI  - AIDS "may dwarf tobacco as killer".

PMID- 11822316
TI  - Second cancers among childhood survivors.

PMID- 11822317
TI  - Privacy and cancer registries in Europe.

PMID- 11822318
TI  - [National Days of Laboratory Medicine of Russia-2001. Scientific and Practical
      Workshop "Philosophy and Methods of Laboratory Support of Outpatient Care and
      Current Problems of Laboratory Medicine". Abstracts].

PMID- 11822319
TI  - [Nocturnal dyspnea attacks].

PMID- 11822320
TI  - Angels unaware--a pediatric Christmas story.

PMID- 11822321
TI  - Too hasty operations following accidents. 1918.

PMID- 11822322
TI  - Proceedings of the International Conference on West Nile Virus. April 5-7, 2001.
      White Plains, New York, USA.

PMID- 11822323
TI  - FDA regulation of ingredients in dietary supplements after passage of the Dietary
      Supplement Health and Education Act of 1994: an update.

PMID- 11822324
TI  - Regulating dietary supplement safety under the dietary supplement health and
      education act: brave new world or pyrrhic victory?

PMID- 11822325
TI  - Constitutional protection of commercial speech under the Central Hudson test as
      applied to health claims.

PMID- 11822326
TI  - Forces reshaping the performance and contribution of the U.S. medical device
      industry.

PMID- 11822327
TI  - The use of standards is the name of the game.

PMID- 11822328
TI  - The U.S. medical device industry: entrepreneurs' future hinges on reforms at the
      Food and Drug Administration.

PMID- 11822329
TI  - Commentary: funding is not the only factor.

PMID- 11822330
TI  - Commentary: same price, better care.

PMID- 11822331
TI  - Commentary: competition made them do it.

PMID- 11822332
TI  - GMC member forced to stand down from disciplinary panel. GMC member responds.

PMID- 11822333
TI  - GMC member forced to stand down from disciplinary panel. Colman's withdrawal from
      committee is issue of organisational governance.

PMID- 11822334
TI  - GMC member forced to stand down from disciplinary panel. GMC should have
      protected Colman.

PMID- 11822335
TI  - Maintaining the integrity of the scientific record. Scientific standards observed
      by medical journals can still be improved.

PMID- 11822336
TI  - Maintaining the integrity of the scientific record. New policy is unlikely to
      give investigators more control over studies.

PMID- 11822337
TI  - Anaesthetic machines and anti-hypoxia devices. Interim solution is to remove
      nitrous oxide cylinders and pipelines and cap their connections.

PMID- 11822338
TI  - Anaesthetic machines and anti-hypoxia devices. When is an anti-hypoxia device not
      an anti-hypoxia device?

PMID- 11822339
TI  - Doctors must read drug labels, not whinge about them.

PMID- 11822340
TI  - Safety of acupuncture. Incident reporting and feedback may reduce risks.

PMID- 11822341
TI  - Complexity science. Let them eat complexity: the emperor's new toolkit.

PMID- 11822342
TI  - Complexity science. New approaches to evaluation of treatment are needed.

PMID- 11822343
TI  - Prevalence of permanent childhood hearing impairment. Family friendly hearing
      services are needed in the United Kingdom.

PMID- 11822344
TI  - Prevalence of permanent childhood hearing impairment. Pilot programme in
      Australia shows promising results.

PMID- 11822345
TI  - Biophysical Society 46th Annual Meeting. February 23-27, 2002. San Francisco,
      California, USA. Abstracts.

PMID- 11822346
TI  - Outpatient treatment of venous thromboembolism with low-molecular-weight heparin:
      an economic evaluation.
AB  - BACKGROUND: The development of low-molecular-weight heparins (LMWHs) has made it
      possible to shift treatment of deep vein thrombosis (DVT) from inpatient to
      outpatient settings, thereby saving costs and improving patient quality of life.
      OBJECTIVE: To quantify the economic benefits of early discharge of patients
      treated for DVT with LMWH using data pooled from multiple healthcare plans.
      METHODS: Data sources were integrated medical and pharmacy claims paid by 37 US
      health plans (the PharMetrics Integrated Outcomes Database, PharMetrics, Inc.,
      Watertown, MA). Hospitalized patients discharged with a diagnosis of DVT were
      selected and grouped according to the anticoagulation therapy they received after
      discharge. Outcomes and costs of DVT treatment were assessed over a 1-year
      period. RESULTS: Patients discharged on the LMWH enoxaparin and warfarin spent
      2.6 fewer days in the hospital than those discharged on warfarin alone (P<
      .0001), resulting in cost savings of $1911 per patient. Mean costs of outpatient
      management of DVT, including pharmacy and medical services, were $901 higher in
      the enoxaparin/warfarin cohort, but rate of readmission was lower (6.7% versus
      9.0%; P < .05) and hence subsequent inpatient costs were reduced by $140 per
      patient. Total cost savings in the enoxaparin/warfarin cohort, net of higher
      outpatient costs, were $1151 per patient. CONCLUSIONS: Outpatient anticoagulation
      therapy for DVT with enoxaparin and warfarin is associated with earlier hospital
      discharge, fewer readmissions, and lower total DVT-related costs compared with
      warfarin monotherapy.

PMID- 11822347
TI  - Use of managed care claims data in the risk assessment of venous thromboembolism
      in outpatients.
AB  - BACKGROUND: Deep vein thrombosis (DVT) is a complication of immobilizing illness
      in both inpatient and outpatient settings and can lead to serious complications
      such as pulmonary embolism (PE). DVT and PE are collectively referred to as
      venous thromboembolism. OBJECTIVE: To develop DVT and PE risk assessment models
      that can be used in office-based practice and for population-based disease
      management efforts. METHODS: Data were culled from integrated medical and
      pharmacy claims paid by 37 health plans in the United States (the PharMetrics
      Integrated Outcomes Database, PharMetrics Inc., Watertown, MA), and included
      information on adult plan members enrolled during 1998 and 1999. Patients
      hospitalized for DVT or PE in 1999 were identified, and potential risk factors
      were assessed by reviewing claims for the entire study population in 1998 to
      document prior DVT or immobilizing illness. The contribution of each potential
      risk factor to the probability of the occurrence of DVT or PE was determined by
      means of multiple logistic regression analysis. A risk-scoring algorithm based on
      regression coefficients was then developed. RESULTS: Fifty-two percent of the
      study population of 2.8 million plan members were women. DVT or PE occurred in
      1330 of those 2.8 million individuals (47 per 100,000). Logistic regression
      results confirmed the role of risk factors previously reported in the literature
      and revealed additional risk factors that have not been reported previously,
      including diabetes, renal failure, rheumatoid arthritis, cellulitis, use of
      warfarin, use of systemic corticosteroids, and use of potassium chloride. When
      risk scores were applied to the study population, the 1% identified as being at
      highest risk had a probability for the development of venous thromboembolism that
      was 10 times greater than that of the population average. CONCLUSIONS: This study
      confirms the feasibility of using managed care claims data to develop a risk
      assessment tool for venous thromboembolism that can be used in office-based
      practice and for population-based disease management.

PMID- 11822348
TI  - Abstracts of the annual conference of the British Association of Sport and
      Exercise Sciences. Newport, 4-7 September 2001.

PMID- 11822349
TI  - Abstracts of the 1st Polish Molecular Biotechnology Conference and the 3rd
      Seminar of Polish Biotechnology Students' Scientific Circles. 18-20 October 2001,
      Gdansk.

PMID- 11822350
TI  - Antipsychotics and single-cell activity in the rat superior colliculus.
AB  - Schizophrenic patients have problems with saccadic eye movements that can be
      characterized as a loss of control over the saccadic system. Preliminary clinical
      results suggest that antipsychotics can either disrupt or improve saccadic
      performance. The brain mechanism through which antipsychotics might affect
      saccades is the subject of study. The superior colliculus (SC) is crucially
      involved in the generation of saccades. Previous experimental studies showed that
      the substantia nigra reticulata (SNr), a structure with profound inhibitory
      influence on the SC, is differentially affected by classical and atypical
      antipsychotics. In this study, we investigated the potential effects of atypical
      antipsychotics (clozapine, olanzapine, and risperidone) and a classical
      antipsychotic (haloperidol) on the firing rate of SC cells in the rat. In
      anesthetized rats, we performed extracellular recordings on spontaneous active
      neurons in the intermediate and deep layers of the SC. After subcutaneous
      injection of an antipsychotic drug, changes in firing rate were compared with
      responses upon saline injection. Olanzapine (1.0 mg/kg), risperidone (0.3 and 1.0
      mg/kg), and haloperidol (0.5 mg/kg) did not significantly alter cell activity,
      but clozapine (10.0 mg/kg) induced a short-lasting but significant decrease.
      Except for clozapine, the effects of antipsychotics on the SC were nonsignificant
      and therefore independent of the effects in the SNr. Our results support the
      notion that clozapine is different from the other atypical antipsychotics.

PMID- 11822351
TI  - Tolerability of fluoxetine in posttraumatic stress disorder.
AB  - PURPOSE: In response to earlier reports that raised concerns about the
      tolerability of fluoxetine in the treatment of posttraumatic stress disorder
      (PTSD), this study was conducted to systematically delineate treatment-emergent
      symptoms (TES) associated with fluoxetine treatment of PTSD. METHODS: Sixty-five
      patients with PTSD enrolled in one of two identical-protocol, 12-week studies and
      received double-blind fluoxetine or placebo. TES data were obtained using a
      patient-rated checklist, Severity of Symptoms Scale (SOSS). RESULTS: Only a
      single patient discontinued treatment due to medication side effects. Compared to
      placebo, only three statistically significant TES (nausea, diarrhea, and thirst)
      occurred more frequently in fluoxetine subjects. Fluoxetine was not associated
      with any statistically significant activating effects. There were no
      statistically significant associations between the total number of TES
      experienced and treatment, gender, or comorbid depressive or panic disorders.
      CONCLUSIONS: This systematic assessment of TES indicated that PTSD patients
      tolerated fluoxetine well without pronounced activating side effects.

PMID- 11822352
TI  - The mitochondrial toxin 3-nitropropionic acid aggravates reserpine-induced oral
      dyskinesia in rats.
AB  - The effects of a previous long-term administration of the mitochondrial toxin 3
      nitropropionic acid were studied on an animal model of tardive dyskinesia, i.e.,
      the frequency of spontaneous tongue protrusions in rats repeatedly treated with
      reserpine. 3-Nitropropionic acid (10 or 15 mg/kg i.p., every other day for 17
      days) potentiated the increase in tongue-protrusion frequency induced by
      reserpine (1 mg/kg, s.c., every other day for 3 days) but did not modify
      reserpine-induced increase in immobility duration and decrease in locomotion
      frequency. These results support the notion that neurotoxic events are associated
      with the development of tardive dyskinesia.

PMID- 11822353
TI  - A meeting of minds in proteomics.

PMID- 11822354
TI  - Low-prime perfusion circuit and autologous priming in CABG surgery on a Jehovah's
      Witness: a case report.
AB  - Cardiac surgery on Jehovah's Witnesses is a great challenge for the
      cardiothoracic surgery team and especially for the perfusionist. To reduce the
      risk of surgery in these patients, a very small extracorporeal circuit was
      designed to decrease the amount of priming volume and thereby the degree of
      hemodilution. A small bypass system was built, consisting of a 3/8-in. arterial
      line and a 3/8-in. venous line, a venous collapsible reservoir, a centrifugal
      pump, a hollow fiber oxygenator and a cell saver reservoir. The circuit priming
      volume was 650 ml. By using antegrade and retrograde autologous priming, the
      total amount of priming was reduced to +/-50 ml. Bypass time was 63 min with an
      average blood flow of 5300+/-114 ml/min and postmembrane pressures of 180+/-45
      mmHg. Venous line pressure was monitored and kept between -8 and -20 mmHg with a
      mean arterial pressure (MAP) of 55+/-12.3 mmHg. The hematocrit before
      extracorporeal circulation (ECC) was 36%, per-ECC 35% and post-ECC 35%. On the
      fifth postoperative day, the hematocrit was 40%. The patient was discharged 7
      days after surgery. A low-prime circuit, in combination with autologous priming,
      seems to be safe and effective in avoiding the use of banked blood.

PMID- 11822355
TI  - Proceedings of the Physiological Society meeting held at University of Aberdeen,
      6-8 September 2000.

PMID- 11822356
TI  - Annual cumulative alphabetical and subject matter index.

PMID- 11822357
TI  - Cumulative 24-year index. Volumes 1-24, 1978-2001.

PMID- 11822358
TI  - [Cholinergic regulation of the sea urchin embryonic and larval development].
AB  - Choline esters of polyenoic fatty acids block cleavage divisions of sea urchins
      and evoke the formation of one-cell multinuclear embryos. If the fatty acids AA
      Ch or DHA-Ch are added at the mid or late blastula stage, many cells are
      extruded, forming extra-embryonic cell clusters near the animal pole of embryos
      or larvae. Both effects are prevented by dimethylaminoethyl esters of polyenoic
      fatty acids (AA-DMAE or DHA-DMAE) or their 5-hydroxytryptamides. Nicotinic
      acetylcholine receptor antagonists, imechine, d-tubocurarine or QX-222 provide
      partial protection against AA-Ch or DHA-Ch. The organophosphate pesticide,
      chlorpyrifos, or a combination of (-)-nicotine + phorbol 12-myristate 13-acetate,
      also evoke the mass extrusion of transformed embryonic cells at the animal pole
      of larvae. These effects are similarly antagonized by AA-DMAE, DHA-DMAE, or fatty
      acids 5-hydroxytryptamides. Taking together, these results suggest that AA-Ch and
      DHA-Ch act on sea urchin embryos and larvae as agonists of acetylcholine
      receptors, whereas AA-DMAE and DHA-DMAE act as antagonists. The ability of fatty
      acids 5-hydroxytryptamides to prevent the effects of AA-Ch or DHA-Ch may be due
      to restoration of the normal dynamic balance of cholinergic and serotonergic
      signaling during cleavage divisions and gastrulation.

PMID- 11822359
TI  - Bone-marrow-derived cells contribute to endothelial repair after thrombotic
      microangiopathy.

PMID- 11822360
TI  - Treatment of painful sickle cell leg ulcers with topical opioids.

PMID- 11822361
TI  - Sustained response of refractory chronic lymphocytic leukemia in progression
      complicated by acute hemolitic anemia to anti-CD20 monoclonal antibody.

PMID- 11822362
TI  - Recurrent coiled-coil motifs in NUP98 fusion partners provide a clue to
      leukemogenesis.

PMID- 11822363
TI  - Effects of cyclic temperature changes on hardness of composite restoratives.
AB  - The clinical durability of some composite restorative materials may be
      significantly affected by cyclic temperature changes. This study investigated the
      effects of cyclic temperature changes on surface hardness of four commercial
      composite resins (Silux, Z100, Ariston and Surefil). Eighteen specimens of each
      material were divided into three treatment groups comprising a control and two
      different thermal cycling regimes. Control specimens were stored in distilled
      water at 35 degrees C for 178 hours. Thermal cycled specimens were stored in
      distilled water at 35 degrees C for 173 hours and subjected to five hours (300
      cycles) of a thermal cycling regime consisting of the cycle ABAC, where A and B
      represent the fixed temperatures of 35 degrees C (28 seconds) and 15 degrees C
      (two seconds) and C, depending on the treatment group, either 45 degrees C or 60
      degrees C (two seconds). All specimens were subsequently subjected to hardness
      testing (KHN) using a digital microhardness tester (load = 500 gf; dwell time =
      15 seconds). Results were analyzed using ANOVA/Scheffe's test (p<0.05). The
      effect of thermal cycling on hardness was material-dependent. While thermal
      cycling significantly increased the surface hardness of Z100 and Surefil, it
      significantly decreased the hardness of Ariston. The hardness of Silux was not
      significantly affected by cyclic temperature changes. For all treatment groups,
      Z100 was significantly harder than the other composite resins evaluated and
      Surefil was significantly harder than Silux and Ariston. For both thermal cycled
      groups, Silux was significantly harder than Ariston.

PMID- 11822364
TI  - Effect of collagen removal on microleakage of resin composite restorations.
AB  - This study evaluated the effects of collagen removal on the microleakage of two
      single-bottle adhesive systems. Forty human third molars were selected and each
      received two root preparations. The roots were randomly assigned for restoration
      using Prime & Bond 2.1 (Dentsply Ltda, Petropolis, RJ 90915, Brazil) or Single
      Bond (3M Dental Products, St Paul, MN 55144, USA). One root in each tooth was
      treated with 36% H3PO4 for 15 seconds and the other received an additional
      treatment with 10% NaOCl for 60 seconds to remove the collagen layer before
      adhesive was applied. All preparations were restored with Z100 restorative resin
      (3M Dental Products). The specimens were submitted to 5,000 thermal cycles (5-55
      degrees C) and stored in 37 degrees C distilled water for one year. The specimens
      were then coated with a varnish except for 1 mm of tooth structure surrounding
      the restoration and immersed in 2% buffered methylene blue for four hours. After
      rinsing, the restorations were sectioned and two independent observers scored the
      microleakage at the interface between the restorative material and the tooth
      using an optical microscope at x45 magnification. The scores were submitted to
      Fisher's Exact Test and the results showed that collagen removal significantly
      reduced microleakage for Prime & Bond 2.1 and had no effect on microleakage for
      Single Bond.

PMID- 11822365
TI  - Effectiveness of composite cure with pulse activation and soft-start
      polymerization.
AB  - The study investigated the effectiveness of composite cure with pulse activation
      and soft-start polymerization. A light-cure unit (BISCO VIP, BISCO Dental
      Products, Schaumburg, IL 60193, USA) that allowed for independent command over
      time and intensity was used. The six light-curing modes examined were: Control
      (C)-400 mW/cm2 [40 seconds]; Pulse Delay I (PDI) -100 mW/cm2 [3 seconds] -->
      delay [3 minutes] --> 500 mW/cm2 [30 seconds]; Pulse Delay II (PDII) - 200 mW/cm2
      [20 seconds] --> delay [3 minutes] --> 500 mW/cm2 [30 seconds]; Soft-start (SS) -
      200 mW/cm2 [10 seconds] --> 600 mW/cm2 [30 seconds]; Pulse Cure I (PCI) - 400
      mW/cm2 [10 seconds] --> delay [10 seconds] --> 400 mW/cm2 [10 seconds] --> delay
      [10 seconds] --> 400 mW/cm2 [20 seconds]; and Pulse Cure II (PCII) - 400 mW/cm2
      [20 seconds] --> delay [20 seconds] --> 400 mW/cm2 [20 seconds]. Effectiveness of
      cure with the different modes was determined by measuring the top and bottom
      surface hardness of 2 mm thick composite (Z100) specimens using a digital
      microhardness tester (load=500 gf; dwell time=15 seconds). The effectiveness of
      cure of the bottom surface of the composite was also established by Fourier
      Transform Infrared (FTIR) spectroscopy using the KBr technique. Data obtained was
      analyzed using one-way ANOVA/Scheffe's post-hoc test (p<0.05). No significant
      difference in top Knoops Hardness Number KHN wa s observed except for PDIand
      PDII. At the bottom surfaces, KHN obtained with the control was significantly
      greater than with PDII, SS and PCII. FTIR results ranked well with the hardness
      of the bottom surfaces. The absorbance ratio of carbon double bonds to aromatic
      ring obtained with the control group was significantly greater than with PDII and
      PCII. Effectiveness of the cure at the bottom surfaces of composites may be
      reduced by some pulse activation and soft-start polymerization regimens.

PMID- 11822367
TI  - [Value of MRCP for detection of choledocholithiasis in symptomatic patients: one
      year experience with a standardized high resolution breath-hold technique].
AB  - In our institution, MRCP is actually replacing diagnostic ERCP. This study is
      addressing its accuracy in the diagnosis of symptomatic choledocholithiasis. 137
      MRCP were performed in patients with upper abdominal pain and biological
      anomalies (n = 48), pain with cholelithiasis at sonography (n = 69) or non
      alcoholic acute pancreatitis (n = 20) on a 1.5 T system with high gradients using
      a standardized combination of breath-hold HASTE and RARE sequences. We included
      in our study 74 patients who underwent as second test ERCP (n = 36), peroperative
      cholangiography (n = 13), or extensive follow-up with laboratory tests and/or
      sonography (n = 25). All examinations were judged as diagnostic, discrepancies
      between direct cholangiography and MRCP being noted in 4 patients (5.4%).
      Lithiasis was misinterpreted on MRCP as bubbles in 2 patients after
      sphincterotomy or surgery. We had two false positive diagnoses on MRCP: in one
      patient peroperative cholangiography was negative and in the other one ERCP was
      negative. With a sensitivity and PPV of 92%, a specificity and NPV of 96% MRCP in
      our experience is shown as an accurate diagnostic tool for the detection of stone
      in the common bile duct replacing ERCP.

PMID- 11822366
TI  - Post-gel shrinkage with pulse activation and soft-start polymerization.
AB  - This study investigated the influence of pulse activation and soft-start
      polymerization regimens on the post-gel shrinkage of a visible light-activated
      composite resin (Z100). A light-cure unit (BISCO VIP) that allowed for
      independent command over time and intensity was used. The six light-curing modes
      that were examined include: Control (C)-400 mW/cm2 [40 seconds]; Pulse Delay I
      (PDI)-100 mW/cm2 [3 seconds], delay [3 minutes], 500 mW/cm2 [30 seconds]; Pulse
      Delay II (PDII)-200 mW/cm2 [20 seconds], delay [3 minutes], 500 mW/cm2 [30
      seconds]; Soft-start (SS)-200 mW/cm2 [10 seconds], 600 mW/cm2 [30 seconds]; Pulse
      Cure I (PCI)--two 400 mW/cm2 [10 seconds] and one 400 mW/cm2 [20 seconds] pulses
      with 10 seconds interval between; and Pulse Cure II (PCII)-two 400 mW/cm2 [20
      seconds] pulses with 20 seconds interval between. A strain-monitoring device
      measured the linear polymerization shrinkage associated with the various cure
      modes during and post light polymerization up to 60 minutes. Five specimens were
      made for each cure mode. Data was analyzed using one-way ANOVA and Scheffe's post
      hoc test at significance level 0.05. Post-gel shrinkage associated with PDI was
      significantly lower than with PDII, SS and PCI immediately post light
      polymerization. At one-minute post light polymerization, PDI had significantly
      lower shrinkage compared to PDII and SS. Significant differences in shrinkage
      were observed between PDI and SS only at 10, 30 and 60 minutes. At all time
      intervals, no significance in post-gel shrinkage was observed between the control
      and all-pulse activation/soft-start polymerization regimens.

PMID- 11822368
TI  - [Myositis ossificans and other ossifying lesions of the soft tissues].
AB  - Knowledge of the clinical history and typical imaging characteristics of myositis
      ossificans is important as identification of this entity will avoid unnecessary
      and invasive work-up. Conversely, the radiologist must pay attention to any
      atypical clinical or imaging finding, which will warrant further investigations.

PMID- 11822369
TI  - Initial investigations into two viruses isolated from marine food fish in
      Singapore.

PMID- 11822371
TI  - Biochemical Society 675th Meeting, joint with the Physiological Society. York,
      United Kingdom. December 2001. Abstracts.

PMID- 11822370
TI  - Isolation of Enterococcus cecorum from bone lesions in broiler chickens.

PMID- 11822372
TI  - Reproductive efficiency of intensively managed Thoroughbred mares in Newmarket.
AB  - The findings of a retrospective survey of 1393 Thoroughbred mares visiting 22
      studfarms in the Newmarket region of the UK during the 1998 mating season were
      compared with those of a similar study undertaken in 1983. The effects of mare
      age and status, stallion, month of mating, application of uterine treatments and
      other parameters on the rates of singleton and twin conception and subsequent
      pregnancy losses were analysed. Mare age and status significantly affected the
      per cycle pregnancy rate and the incidence of pregnancy loss. Overall, the mean
      number of matings per oestrus was 1.12 and the mean number of times a mare was
      mated until diagnosed pregnant at 15 days after ovulation was 1.88. An overall
      mean per cycle pregnancy rate of 59.9% at 15 days after ovulation resulted in
      94.8% of the mated mares being pregnant at least once at 15 days after ovulation.
      This high initial pregnancy rate fell to 89.7% by Day 35 and 87.5% by the time of
      the October pregnancy test; 82.7% of the mares surveyed gave birth to a live foal
      at term, which compares favourably with the proportion of mares foaling in 1983
      (77%). However, despite improvements in the foaling rates over the last 15 years,
      the overall rate of pregnancy failure remains high and represents a major loss to
      the Thoroughbred breeding industry.

PMID- 11822373
TI  - Plasma and synovial fluid concentrations of calcium pentosan polysulphate
      achieved in the horse following intramuscular injection.
AB  - Results from in vitro studies have indicated that calcium pentosan polysulphate
      (CaPPS) may be of therapeutic value in osteoarthritis (OA) in the horse. However,
      no controlled clinical trials using this drug in equine OA have yet been
      reported. If CaPPS is to be developed for such use, the relationship between the
      proposed i.m. dose of CaPPS to be used and the concentrations of drug attained in
      plasma and synovial fluid of the target joint should first be established. An
      investigation was undertaken to determine these concentrations after a single 2
      mg/kg i.m. injection of CaPPS. Blood and synovial fluid samples were taken from 6
      healthy, sound horses following i.m. CaPPS administration. Concentrations of
      CaPPS measured in the synovial fluid were, on the basis of published studies,
      sufficient to elicit a potential therapeutic effect on synoviocyte metabolism,
      and possibly also to stimulate proteoglycan synthesis and reduce matrix
      metalloproteinase activities in articular cartilage. It would therefore seem
      justified to investigate further the therapeutic effect of CaPPS in OA in the
      horse.

PMID- 11822374
TI  - Analysis of purines and pyrimidines by mixed partition-adsorption normal-phase
      high-performance liquid chromatography.
AB  - This paper summarizes the results in the development of mixed partition
      adsorption (MPA) normal-phase high-performance liquid chromatography published in
      the last 10 years. The MPA normal-phase systems are an alternative approach not
      only to the adsorption normal-phase mode but also to the most widely used
      reversed-phase mode in the separation area of purine and pyrimidine derivatives.
      It is shown that the MPA systems are applicable in analytical practice.

PMID- 11822375
TI  - Analytical and semipreparative enantiomeric separation of azole antifungal agents
      by high-performance liquid chromatography on polysaccharide-based chiral
      stationary phases. Application to in vitro biological studies.
AB  - High-performance liquid chromatography (HPLC) was used for the enantiomeric
      separation of chiral imidazole derivatives endowed with antimycotic activity.
      Enantioselective columns, containing carbamates of cellulose and amylose, were
      used. The influence of the nature and content of an alcoholic modifier in the
      mobile phase was studied. The isolated enantiomers, separated on semipreparative
      columns, were submitted to in vitro biological investigations.

PMID- 11822376
TI  - Use of ionic polymers as stationary and pseudo-stationary phases in the
      separation of ions by capillary electrophoresis and capillary
      electrochromatography.
AB  - One of the problems with capillary electrophoresis is a lack of versatility
      regarding manipulation of the separation selectivity. A new and potentially
      universal concept is to introduce an ion-exchange component into a separation so
      that the migration of analyte ions is influenced by both their electrophoretic
      mobilities and their chromatographic properties. This may be accomplished by use
      of capillaries filled with or coated with solid ion-exchange polymers, or by
      addition of a soluble ionic polymer to the background electrolyte to create a
      pseudo-stationary phase. While each of these methods achieves the same result,
      they are not competitive, but rather complementary as the problems associated by
      one approach are overcome by the others. Recent highlights in the field are used
      to illustrate the flexibility that this approach provides to electrophoretic
      separation of ions.

PMID- 11822377
TI  - High-resolution chiral separation using microfluidics-based membrane
      chromatography.
AB  - A plastic microfluidic system, containing porous poly(vinylidene fluoride) (PVDF)
      membranes adsorbed with bovine serum albumin (BSA), is demonstrated for high
      resolution chiral separation of racemic tryptophan and thiopental mixtures.
      Microfluidic networks on poly(dimethylsiloxane) (PDMS) substrates are fabricated
      by capillary molding technique. This miniaturized chiral separation system
      consists of two layers of PVDF membranes which are sandwiched between two PDMS
      slabs containing microchannels facing the membranes. On-line adsorption of BSA
      onto the membranes is employed for the preparation of chiral stationary phase and
      the evaluation of solution conditions in an effort to achieve maximum protein
      adsorption. Variations in the mobile phase conditions, including solution pH and
      ammonium sulfate concentration, are studied for their effects on chiral
      separation. Based on the large surface area to volume ratio of porous membrane
      media, adsorbed BSA onto the PVDF membranes enables high resolution separation of
      racemic mixtures with sample consumption of sub-nanogram or less in the
      integrated microfluidic networks. In addition, the membrane pore diameter in the
      submicron range eliminates the constraints of diffusional mass-transfer
      resistance during protein adsorption and chiral chromatographic processes.

PMID- 11822379
TI  - Development of a peptide mapping procedure to identify and quantify methionine
      oxidation in recombinant human alpha1-antitrypsin.
AB  - A peptide mapping procedure was developed to identify and quantify methionine
      oxidation in recombinant human alpha1-antitrypsin. Due to the protein's complex
      structural biochemistry, chromatographic analysis of methionine containing digest
      peptides was a significant challenge. However, by using a combination of mass
      spectrometry, protein engineering, and high-temperature reversed-phase liquid
      chromatography, we were able to identify methionine residues that are susceptible
      to oxidation by hydrogen peroxide. and quantify their reactivity. Our results
      show that five of the protein's 10 methionine residues are susceptible to
      oxidation at neutral pH, four of which are localized to the active site region.

PMID- 11822378
TI  - Direct capture of product from fermentation broth using a cell-repelling ion
      exchanger.
AB  - A new technique for treating anion exchangers has been proposed allowing direct
      capture of the fermentation product, shikimic acid directly from the cell
      containing fermentation broth. A layer of hydrophilic polymer, poly(acrylic acid)
      (PAA) has been physically adsorbed on the anion exchanger followed by a covalent
      cross-linking of PAA. The PAA layer is penetrable for small molecules despite
      being negatively charged as PAA is, but the polymer layer repels large negatively
      charged structures like cell debris and cells preventing them from adsorption to
      the chromatographic matrix. The binding capacity for pure shikimic was about 81
      mg/ml adsorbent for both cross-linked PAA-Amberlite and native Amberlite in the
      fluidized mode of column operation. Binding capacity dropped to 17 and 15 mg per
      ml adsorbent, respectively, when using filtrated fermentation broth and to about
      10 mg/ml adsorbent for cross-linked PAA-Amberlite when using directly the
      fermentation broth containing cells. Native Amberlite cannot be used for the
      direct capture of shikimic acid due to the immediate clogging of the column and
      the collapse of the expanded bed. The cross-linked PAA-Amberlite was used
      repeatedly for the direct adsorption of shikimic acid from the industrial
      fermentation broth.

PMID- 11822380
TI  - pKa values of peptides in aqueous and aqueous-organic media. Prediction of
      chromatographic and electrophoretic behaviour.
AB  - In the present work, models describing the effect of the pH on the
      chromatographic and electrophoretic behaviour for polyprotic peptides were
      compared. The proposed models can be simultaneously used for determination of
      dissociation constants and selection of the optimum pH for the separation of
      peptides, in water and acetonitrile-water mixtures widely used in liquid
      chromatography and in capillary electrophoresis. The models use the pH value
      measured in the acetonitrile-water mixture instead of the pH value in water and
      take into account the effect of the activity coefficients. They permit the
      determination of the acidity constants in the aqueous and hydro-organic mobile
      phase from chromatographic retention and electrophoretic migration measurements,
      respectively. The values obtained by both proposed techniques agree with the
      potentiometric values previously determined. The suitability of the proposed
      models for predicting chromatographic and electrophoretic behaviour of compounds
      studied from a limited number of experimental data was also compared. The
      separation between solutes by both techniques in a complex mixture can be easily
      predicted, making simple and rapid pH selection to achieve optimum separation.

PMID- 11822381
TI  - Strategy for highly selective ion-exchange capture using a charge-polarizing
      fusion partner.
AB  - To achieve efficient recovery of recombinantly produced target proteins using
      cation-exchange chromatography, a novel basic protein domain is used as a
      purification handle. The proteolytic instability usually encountered for basic
      peptide tags is avoided by the use of a highly constrained alpha-helical domain
      based on staphylococcal protein A into which positively charged amino acids have
      been introduced. Here we show that this domain, consisting of 58 amino acids with
      a calculated isoelectric point (pI) of 10.5, can be used to efficiently capture
      different fused target proteins, such as a bacterial DNA polymerase (Klenow
      fragment), a viral protease (3C) and a fungal lipase (Cutinase). In contrast to
      standard cation-exchange chromatography, efficient capture can be achieved also
      at a pH value higher than the pI of the fusion protein, demonstrated here by
      Zbasic-Klenow polymerase (pI approximately/= 5.8) and ZZ-Cutinase-Zbasic (pI
      approximately/= 7.2) both purified at a pH of 7.5. These results show that the
      Zbasic domain is able to confer a regional concentration of positive charge on
      the fusion protein even at a relatively high pH. Hence, the data suggest that
      this domain could be used for highly efficient and selective capture of target
      proteins at conditions where most host-cell proteins do not bind to the
      chromatographic resin. The obtained purity after this one-step procedure suggests
      that the strategy could be an alternative to standard affinity chromatography.
      Methods for site-specific proteolysis of the fusion proteins to release native
      target proteins are also discussed.

PMID- 11822382
TI  - DNA-support coupling for transcription factor purification. Comparison of
      aldehyde, cyanogen bromide and N-hydroxysuccinimide chemistries.
AB  - Purification of transcription factor IIIA on internal control region DNA coupled
      to aldehyde-silica is described and compared with purification on cyanogen
      bromide-activated Sepharose and Bio-Rad Affi-Gel-10. The Affi-Gel support results
      in mixed-mode chromatography; both ion-exchange and affinity modes contribute.
      Coupling DNA to aldehyde-silica is advantageous in that it has no ion-exchange
      properties and performs as well as DNA coupled to CNBr-activated Sepharose.
      Purification of lac repressor on aldehyde-silica, and CAAT enhancer binding
      protein on Affi-Gel also shows the advantages of a neutral support and the
      disadvantages of mixed-mode chromatography for transcription factor purification.
      Aldehyde-silica couples to alkylamines and to the amines of adenine, guanine, and
      cytosine nucleoside bases. Reaction occurs with either single- or double-stranded
      DNA, although it is less efficient with the latter. Overall, the results
      demonstrate that predominantly neutral coupling chemistries, such as aldehyde or
      CNBr-mediated coupling, have distinct advantages for transcription factor
      purification. Since the CNBr chemistry has not yet been applied to silica
      supports, aldehyde-silica coupling is currently the most attractive method for
      DNA affinity HPLC.

PMID- 11822383
TI  - Reversed-phase liquid chromatographic determination of phytometallophores from
      Strategy II Fe-uptake species by 9-fluorenylmethyl chloroformate fluorescence.
AB  - An HPLC method to quantitate phytometallophores (phytosiderophores) exuded from
      roots of barley (Hordeum vulgare L.) growing in nutrient solution culture was
      developed. 9-Fluorenylmethyl chloroformate (FMOC) derivatives of
      phytometallophores were separated on a C18 reverse-phase column using a sodium
      acetate (pH 7.2) and acetonitrile-methanol gradient over 20 min followed by
      fluorescence detection. Detection limits ranged from 15 to 370 pmol depending on
      the particular phytometallophore. The effectiveness of this method was
      demonstrated using the response of barley seedlings to Fe-sufficient and Fe
      deficient nutrient solution conditions. Phytometallophores collected in root
      washings of Fe-deficient barley seedlings increased with plant age while
      phytometallophore release from Fe-adequate roots was negligible.

PMID- 11822384
TI  - Determination of phosphonic acid breakdown products by high-performance liquid
      chromatography after derivatization.
AB  - A new HPLC method for the determination of oxidative breakdown products of
      aminopolyphosphonates is presented. The phosphonate
      nitrilotrismethylenephosphonic (NTMP) acid undergoes catalytic oxidation by
      molecular oxygen in the presence of manganese(II). The two diphosphonates
      iminodimethylenephosphonic acid (IDMP) and formyliminodimethylenephosphonic acid
      (FIDMP) are formed. The analytical method employs the derivatization of the
      aldehyde group in FIDMP by 2,4-dinitrophenylhydrazine and of the imine group in
      IDMP by 9-fluorenyl methylchloroformate. The two derivatives are quantified in
      separate runs using the same acidic phosphate-acetonitrile eluent with detection
      at 370 nm for FIDMP and 260 nm for IDMP. The detection limit for FIDMP is 0.01
      microM, for IDMP 0.02 microM. The method is suitable for the determination of the
      breakdown products in wastewater.

PMID- 11822385
TI  - Molecular weight determination of lignosulfonates by size-exclusion
      chromatography and multi-angle laser light scattering.
AB  - A lignosulfonate sample was fractionated according to the solubility in ethanol
      water. The fractions were analysed by aqueous size exclusion chromatography (SEC)
      combined with in-line multi-angle laser light scattering (MALLS), and by static
      MALLS. Satisfactory SEC results were obtained with aqueous phosphate buffer
      containing DMSO and SDS. The refractive index increment (dn/dc) varied from 0.186
      to 0.205 ml/g, depending on Mw and the degree of sulfonation. The second viral
      coefficient (A2) was 7 x 10(-3) ml mol/g2. The weight-average molecular weight
      (Mw) of the fractions varied from 4600 up to 398 000 g/mol. and the
      polydispersity (Mw/Mn) varied between 1.3 and 3.5.

PMID- 11822386
TI  - Considerations on the temperature dependence of the gas-liquid chromatographic
      retention.
AB  - A discussion on the temperature dependence of the partition coefficient K is
      developed. This discussion embraces topics such as the limitations of
      conventional thermodynamic approaches followed in the chromatographic literature,
      qualitative theoretical notions arising from molecular thermodynamics and the
      experimental information that is accessible through modern capillary gas
      chromatography. It is shown that the heat capacity difference of solute transfer
      for flexible molecules has at least one maximum in the chromatographic range of
      temperature. As a consequence, a great amount of experimental data is required
      for a correct thermodynamic interpretation of the chromatographic retention.

PMID- 11822387
TI  - Determination of linear alkylbenzenes in fish tissue by gel permeation
      chromatography and gas chromatography-mass spectrometry.
AB  - A gel permeation chromatographic (GPC) procedure is described for separation of
      the long-chain linear alkylbenzenes (LABs) from fish muscle tissues. This
      technique was found to remove the matrix interference significantly and thereby
      improve the sensitivity of detection of LABs in the extracts. Gas chromatography
      mass spectrometry (GC-MS) was then used to quantitate LABs in different species
      of fish and also fish from different locations on a transect from the outfalls
      from the Orange County Sanitation Districts, in the coastal waters of Southern
      California. The results are consistent with the proximity of the (sewage) source.
      The data, thus, show that LAB contents in fish tissues, especially that from
      white croaker (Genyonemus lineatus) are useful in assessing exposure to sewage
      residues in the marine waters. This method of concentrating LABs by GPC could be
      applicable to all other similar biological matrices.

PMID- 11822388
TI  - Flame ionization detection after splitting the water effluent in subcritical
      water chromatography.
AB  - The coupling of subcritical water separation with flame ionization detection
      (FID) in the split mode has been investigated in this study. In order to keep the
      FID system stable during subcritical water separation, a Tee union was connected
      between the separation column and the FID system to split the water flow. The
      ratio of the water flow to the FID system over the flow-rate to a waste bottle
      varied depending on the dimension of capillary tubings and the total water flow
      rate used. Separations of several carbohydrates, carboxylic acids, and amino
      acids were performed on commercially available columns using a laboratory-made
      subcritical water chromatography-FID system. The FID system was very stable in
      this split mode even at total flow-rate as high as 1.24 ml/min. The linear
      dynamic range was up to three orders of magnitude and the limit of detection
      (LOD) ranged from 38 to 111 ng (306-925 ng/microl injected) with split ratios of
      approximately 1:10 to approximately 1:17 (FID/waste bottle) for several analytes
      studied. However, the LOD can be significantly lowered by adjusting the
      dimensions of the restrictors to allow a higher percentage of the total flow to
      the FID system.

PMID- 11822389
TI  - Solute-solvent interactions in micellar electrokinetic chromatography. III.
      Characterization of the selectivity of micellar electrokinetic chromatography
      systems.
AB  - Several micellar electrokinetic chromatography (MEKC) systems (sodium dodecyl
      sulfate, lithium dodecyl sulfate, lithium perfluorooctanesulfonate, sodium
      cholate, sodium deoxycholate, tetradecyltrimethylammonium bromide and
      hexadecyltrimethylammonium bromide) have been characterized by means of the
      solvation parameter model. It has been observed that the coefficients of the
      correlation equations depend strongly on the particular set of compounds
      analyzed. Principal component analysis has been used to characterize the 2975
      compounds with available solute descriptors and to select an appropriate subset
      of compounds to be analyzed by MEKC. With this set of compounds, the MEKC systems
      have been characterized. Principal component analysis has also been used to show
      the similarities and differences between the properties of the surfactants
      characterized by MEKC.

PMID- 11822390
TI  - Determination of cannabinoids in hair using high-pH* non-aqueous electrolytes and
      electrochemical detection. Some aspects of sensitivity and selectivity.
AB  - Non-aqueous capillary electrophoresis with electrochemical detection (NACE-ED)
      was applied to the determination of cannabinoids in hair. The effect of different
      electrolyte compositions on the selectivity of the separation of
      tetrahydrocannabinol (THC), cannabinol (CBN), cannabidiol (CBD) and
      tetrahydrocannabinol carboxylic acid (THCA) was studied. Complete electrophoretic
      resolution was obtained using a strongly basic background electrolyte consisting
      of 5 mM sodium hydroxide dissolved in acetonitrile-methanol (1:1).
      Electrochemical detection yielded well defined signals in the oxidation mode. In
      order to obtain low limits of detection experimental parameters, which determine
      the sensitivity and the noise level, were optimized. A crucial parameter for
      sensitive measurements using a wall-tube flow cell as end-column detector is the
      distance between the capillary outlet and the working electrode. The highest
      signal-to-noise ratio using a 50 microm I.D. capillary was obtained at a distance
      of 25 microm. When the capillary outlet was moved away from the working
      electrode, thus reducing the strength of the separation field present at the
      working electrode, a large low frequency noise developed. This rise was
      attributed to disturbances of the hydrodynamic pattern in the flow cell.
      Analytical aspects such as sensitivity, reproducibility and selectivity were
      addressed in this work. The precision of NACE-ED regarding migration time and
      peak height for a sample containing 1 microg/ml THC was 0.4% and 1.1% (RSD),
      respectively (n=5). The calibration curve was linear for concentrations ranging
      between 0.1 and 10 microg/ml (r=0.998). The limit of detection for THC was 37
      ng/ml, which is almost two orders of magnitude lower when compared with on-column
      UV detection. The method was evaluated using hair samples containing cannabinoids
      as sample material.

PMID- 11822391
TI  - Rapid determination of caffeine in tea leaves.
AB  - For the purpose of efficient screening of low-caffeine tea shoots, a method for
      the rapid determination of caffeine was developed using high-performance liquid
      chromatography. Polyvinylpolypyrrolidone was packed in a pre-column and used to
      remove polyphenols from tea extracts on-line. The concentrations of caffeine
      extracted from powdered tea leaves at 50 degrees C during 1 day could be analyzed
      in 2-5 min intervals. The pre-column and the analytical column could be used for
      the analysis of more than 2000 samples.

PMID- 11822393
TI  - Rapid determination of volatile constituents of Michelia alba flowers by gas
      chromatography-mass spectrometry with solid-phase microextraction.
AB  - The volatile constituents of Michelia alba flowers, including fresh flowers,
      frozen flowers and withered flowers, were investigated by GC-MS. The volatiles in
      a simulated natural environment were sampled by solid-phase microextraction
      (SPME), with a 100 microm polydimethylsiloxane fiber at 25+/-5 degrees C for 4 h.
      The fibers were desorbed in a GC injection liner at 250 degrees C for 3 min. With
      headspace SPME-GC-MS analysis, 61 peaks were separated. The main compounds in
      headspace of fresh Michelia alba flowers included alpha-myrcene, (S)-limonene,
      (R)-fenchone, linalool, camphor, caryophyllene, germacrene D, etc., a greater
      number of compounds than for frozen flowers and withered flowers. At the same
      time, the biomarkers of fresh flowers were compared with the frozen flowers and
      withered flowers. In this study, headspace SPME-GC-MS afforded a simple and more
      sensitive sampling method for fresh Michelia alba flowers and other fresh
      flowers.

PMID- 11822392
TI  - Fast-scanning fluorescence spectroscopy as a detection system in liquid
      chromatography for confirmatory analysis of flumequine and oxolinic acid.
AB  - Oxolinic acid and flumequine were analysed by reversed-phase liquid
      chromatography after extraction from the sample matrix with dichloromethane and
      partitioning with NaOH. The detection system consisted of a fast-scanning
      fluorescence detector, which provides the full spectra of the eluting peaks and
      can thus be used to confirm the identity of analytes. Determination was performed
      by partial least squares (PLS) and three-way PLS over the three-dimensional data,
      i.e. fluorescence intensity versus retention time and excitation wavelength. In
      both cases, similar results, with prediction errors around 4%, were obtained. The
      method was successfully applied to the analysis of salmon, pork and chicken
      muscle spiked up to 300 ng g(-1).

PMID- 11822394
TI  - Simultaneous determination of inorganic anions, carboxylic and aromatic
      carboxylic acids by capillary zone electrophoresis with direct UV detection.
AB  - Co-electroosmotic capillary zone electrophoresis (CZE) with direct UV detection
      was developed for simultaneous determination of inorganic anions, carboxylic and
      aromatic carboxylic acids. These solutes were separated using a 30 mM phosphate
      buffer containing 1.0 mM tetradecyltrimethylammonium bromide (TTAB) and 20% (v/v)
      acetonitrile at pH of 6.5 and directly detected by UV at 190 nm. Calibration
      curves were linear in the range 0.01-2.0 mM, depending of the solutes. The
      detection limits ranged from 1.0 to 8.0 microM and the relative standards
      deviations (n=5) in range from 1.9 to 3.6% for the peak area. The proposed method
      was used to determine inorganic anions and carboxylic and aromatic acids in soil
      and plant tissue extracts.

PMID- 11822395
TI  - Optimization of headspace sampling using solid-phase microextraction for volatile
      components in tobacco.
AB  - Solid-phase microextraction (SPME) was evaluated as a tool for headspace sampling
      of tobacco samples. Several experimental parameters (e.g. sampling temperature,
      pH, moisture, and the type of SPME fibers) were optimized to improve sampling
      efficiency in two aspects; maximum adsorption and selective adsorption of
      volatile components onto SPME fibers. The effect of these parameters was often
      dominated by the physical and chemical nature (e.g. volatility, polarity) of
      target compounds, thus, SPME sampling conditions can be adjusted to favor a
      selected group of compounds, such as organic acids in tobacco.

PMID- 11822396
TI  - Solid-phase microextraction-gas chromatographic-mass spectrometric method for the
      determination of the fungicides cyprodinil and fludioxonil in white wines.
AB  - A solid-phase microextraction (SPME) followed by a gas chromatographic-mass
      spectrometric (GC-MS) determination has been developed and validated for the
      determination of cyprodinil and fludioxonil in white wine samples. Extraction
      parameters such as the selection of SPME coating, the effect of the temperature,
      the effect of the headspace volume and the salt addition were studied and
      optimized, together with GC-MS analytical conditions. The divinylbenzene-Carboxen
      polydimethylsiloxane (DVB-CAR-PDMS) fiber was the most appropriate for the
      determination of the two pesticides in wine. The quality parameters of the
      proposed method demonstrated a good precision (RSD about 5%), with detection
      limits of 0.1 and 0.2 microg/l for cyprodinil and fludioxonil, respectively.
      Fifteen commercial white wine samples produced in Rias Baixas area in Galicia
      (N.W. Spain) were analyzed with the SPME-GC-MS procedure. Some of the commercial
      wines (75%) presented the two pesticides in concentrations ranging from 0.9 to
      28.6 microg/l. In conclusion, SPME-GC-MS has a great potential for fungicide
      determination in wines.

PMID- 11822397
TI  - Preferential solvation of a dicyanate ester monomer and poly(sulfone) in
      different organic solvents by size-exclusion chromatography.
AB  - Preferential solvation parameters A in the ternary systems solvent (1) -monomer
      (2) -polymer (3) were determined as a tool to measure the compatibility between
      the cyanate ester monomer Arocy B10 and poly(sulfone), PSF, in the presence of
      three organic solvents: tetrahydrofuran, dimethylformamide and dicloromethane.
      The A parameter was measured by size-exclusion chromatography at different
      monomer-to-polymer ratios. The quantitative evaluation was rigorously made at
      polymer-diluted conditions. PSF was found to be preferentially solvated by the
      monomer. Concerning the solvent used, systems containing tetrahydrofuran showed
      the strongest solvation, the lowest A values being those obtained in
      dicloromethane. These results were in accordance with the intrinsic viscosity
      values of the PSF-solvent systems. The variation of A values with the Arocy B10
      concentration is strongly dependent upon the nature of the solvent.

PMID- 11822398
TI  - Temperature-dependent refractive index issues using a UV-visible detector in high
      performance liquid chromatography.
AB  - While studying the properties of some potential, UV-detection compatible, mobile
      phase modifiers for reversed-phase liquid chromatography (RPLC) we encountered
      serious detector baseline problems. The most severe problem was a periodic saw
      tooth-shaped drift. This drift was most noticeable when using water-THF and water
      dioxolane mobile phases. We demonstrate that the baseline problems are related to
      temperature fluctuation in a water bath used to maintain a constant column
      temperature. The temperature fluctuations change the refractive index (RI) of the
      mobile phase, which in turn affects the amount of light reaching the detector.
      Our results show that the magnitude of the baseline drift is related to the RI
      value of the mobile phases. The baseline problems can be alleviated using a
      different temperature controller whose feedback mechanism assures smoother
      operation. Since there is no single and complete source of information in the
      literature concerning the RI values of typical mobile phases in RPLC, we decided
      to measure them as a function of the % modifier (between 0 and 100%) and the
      temperature (between 25 degrees C and 50 degrees C). Knowing the RI values allows
      us to calculate the excess volume of a binary liquid system.

PMID- 11822399
TI  - Ionic strength, pH and temperature effects upon selectivity for transition and
      heavy metal ions when using chelation ion chromatography with an iminodiacetic
      acid bonded silica gel column and simple inorganic eluents.
AB  - An investigation into the selectivity of an iminodiacetic acid (IDA) modified
      silica gel column for transition and heavy metal ions using non-chelating
      inorganic eluents has been carried out. A number of eluent parameters were
      investigated to determine the exact retention mechanism taking place and to
      control selectivity. The parameters studied were eluent ionic strength and the
      nature of the inorganic salt used, eluent pH and eluent temperature. The results
      obtained showed how despite certain metal ions exhibiting similar stability
      constants with the bonded IDA groups, careful control of each of the above
      parameters, in particular eluent chloride ion concentration and eluent
      temperature, could result in large changes in selectivity. Optimal conditions for
      the isocratic and gradient separation of Mg(II), Ca(II), Mn(II), Cd(II), Co(II),
      Zn(II) and Pb(II) were determined. An isocratic method using a 0.035 M KCl, 0.065
      M KNO3 (pH 2.5) eluent was successfully applied to the determination of Mn(II),
      Cd(II), Co(II) and Zn(II) at concentrations between 20 and 121 microg/l in a
      freshwater certified reference material (NIST 1640).

PMID- 11822400
TI  - Chemically modified chiral monolithic silica column prepared by a sol-gel process
      for enantiomeric separation by micro high-performance liquid chromatography.
AB  - In this work a new type of chiral monolith silica column was developed for the
      chiral separation by micro high-performance liquid chromatography (micro-HPLC).
      The chiral monolith column with a continuous skeleton and a large through-pore
      structure was prepared inside a capillary of 100 microm I.D. by a sol-gel
      process, and chemically modified with chiral selectors, such as L
      phenylalaninamide, L-alaninamide and L-prolinamide, on the surface of the
      monolithic silica column. Based on the principle of ligand exchange, these chiral
      monolithic columns were successfully used for the separation of dansyl amino acid
      enantiomers, as well as hydroxy acid enantiomers by micro-HPLC. The
      chromatographic conditions, the enantioselectivity and the performance of columns
      are discussed.

PMID- 11822401
TI  - On the use of genetic algorithms for response surface modeling in high
      performance liquid chromatography and their combination with the Microsoft
      Solver.
AB  - Four genetic algorithms--the classical, Haupt's, Brunetti's and a modification of
      the classical algorithm suggested in the present paper--are examined when they
      are used for the modeling of response surfaces in high-performance liquid
      chromatography (HPLC). We found that the best results are obtained from our
      modification and the worst by Haupt's algorithm. The classical genetic algorithm
      gives satisfactory results, better than those of Brunetti's algorithm. We also
      ascertained that all genetic algorithms may get stuck in a local minimum other
      than the global one, except for our modification, which can be considered to
      approach a global method. Finally, the time needed for the optimization of a
      genetic algorithm and the combination of a genetic algorithm with a non-linear
      least-squares routine are considered and discussed.

PMID- 11822402
TI  - 3rd Brazilian Meeting of Researchers on Alzheimer Disease and Related Disorders.
      24 November 2001. Abstracts.

PMID- 11822404
TI  - 42nd Annual Conference of the Indian Society of Gastroenterology in association
      with the Indian Association for Study of the Liver and the Society of
      Gastrointestinal Endoscopy of India. Lucknow, November 23-29, 2001. Abstracts.

PMID- 11822405
TI  - 5 Aachen Glaucoma Symposium. 24 November 2001. Abstracts.

PMID- 11822403
TI  - Who decides whether a baby lives or dies.

PMID- 11822406
TI  - [Berlin-Brandenburg Ophthalmology Society meeting. 1-2 December 2001. Abstracts].

PMID- 11822407
TI  - Crosslinking by advanced glycation end products increases the stiffness of the
      collagen network in human articular cartilage: a possible mechanism through which
      age is a risk factor for osteoarthritis.
AB  - OBJECTIVE: Age is an important risk factor for osteoarthritis (OA). During aging,
      nonenzymatic glycation results in the accumulation of advanced glycation end
      products (AGEs) in cartilage collagen. We studied the effect of AGE crosslinking
      on the stiffness of the collagen network in human articular cartilage. METHODS:
      To increase AGE levels, human adult articular cartilage was incubated with
      threose. The stiffness of the collagen network was measured as the instantaneous
      deformation (ID) of the cartilage and as the change in tensile stress in the
      collagen network as a function of hydration (osmotic stress technique). AGE
      levels in the collagen network were determined as: Nepsilon
      (carboxy[m]ethyl)lysine, pentosidine, amino acid modification (loss of arginine
      and [hydroxy-]lysine), AGE fluorescence (360/460 nm), and digestibility by
      bacterial collagenase. RESULTS: Incubation of cartilage with threose resulted in
      a dose-dependent increase in AGEs and a concomitant decrease in ID (r = -0.81, P
      < 0.001; up to a 40% decrease at 200 mM threose), i.e., increased stiffness,
      which was confirmed by results from the osmotic stress technique. The decreased
      ID strongly correlated with AGE levels (e.g., AGE fluorescence r = -0.81, P <
      0.0001). Coincubation with arginine or lysine (glycation inhibitors) attenuated
      the threose-induced decrease in ID (P < 0.05). CONCLUSION: Increasing cartilage
      AGE crosslinking by in vitro incubation with threose resulted in increased
      stiffness of the collagen network. Increased stiffness by AGE crosslinking may
      contribute to the age-related failure of the collagen network in human articular
      cartilage to resist damage. Thus, the age-related accumulation of AGE crosslinks
      presents a putative molecular mechanism whereby age is a predisposing factor for
      the development of OA.

PMID- 11822408
TI  - Effect of dynamic strength training on functional capacity in rheumatoid
      arthritis: comment on the article by Hakkinen et al.

PMID- 11822410
TI  - Faculty of Medical Sciences 10th Annual Research Conference and Workshop on
      Ethics in Medical Research and Practice. November 1-2, 2001. Kingston, Jamaica.
      Abstracts.

PMID- 11822411
TI  - [Hippocrates's evaluation of the madness of Democritus].
AB  - Hippocrates is a historical as well as a legendary character. In legends he is
      presented as a personification of the highest intellectual and moral virtues as
      they were understood by the ancient greeks and romans. One of these legends deals
      with a fictitious meeting between him and Democritus, the philosopher. We can
      follow the story in a collection of pseudepigraphic letters from the end of the
      first christian century. On the behalf of the senate of the city of Abdera
      Hippocrates takes upon himself the commission to cure Democritus - the eminent
      son of the city - who is supposed to be mad because he is laughing at everything.
      However, Hippocrates soon realizes that his commission transcends his medical
      profession. Democritus is not mad but a very wise man whose yearn for solitude
      and serenity constrains him to discriminate himself from ordinary people by an
      odd behaviour. He is a melancholic. In these letters we follow a discussion about
      moral and medical aspects of madness and the relationship between the noble
      outsider and his ordinary fellowmen. It is a discussion that points forward at
      recurrent themes in the history of ideas. Hippocrates stands out as a
      philantropist and Democritus as a misanthropist.

PMID- 11822409
TI  - Evidence that rheumatoid arthritis synovial T cells are similar to cytokine
      activated T cells: involvement of phosphatidylinositol 3-kinase and nuclear
      factor kappaB pathways in tumor necrosis factor alpha production in rheumatoid
      arthritis.
AB  - OBJECTIVE: To investigate the mechanism that leads to the spontaneous production
      of tumor necrosis factor alpha (TNFalpha) in rheumatoid arthritis (RA) synovial
      tissue. METHODS: Normal blood monocytes were cocultured either with fixed
      activated T cells generated from normal blood or RA synovial T cells purified
      from synovium. TNFalpha production was measured in supernatants from these
      cocultures following blockade of the transcription factor nuclear factor kappaB
      (NF-kappaB) using adenoviral transfer of the inhibitor of NF-kappaB kinase alpha
      into the responding monocytes, or blockade of phosphatidylinositol 3-kinase (PI 3
      kinase) using the inhibitory drugs wortmannin or LY294002. TNFalpha production
      was measured by enzyme-linked immunosorbent assay. RESULTS: TNFalpha production
      in synovial tissue from patients with RA but not osteoarthritis was found to be T
      cell dependent. The RA synovial joint T cells resembled normal T cells that had
      been activated for 8 days using a cocktail of cytokines. These T cells,
      designated Tck (cytokine-activated T cells), and RA synovial T cells both induced
      TNFalpha production in resting monocytes in a cell-contact-dependent manner,
      which was abrogated by blockage of the transcription factor NF-kappaB but
      augmented if PI 3-kinase was inhibited. Normal blood T cells activated
      conventionally via the T cell receptor with crosslinked anti-CD3 antibody
      resulted in TNFalpha production from monocytes; this was unaffected by NF-kappaB
      blockade, but was inhibited in the presence of PI 3-kinase-blocking drugs.
      CONCLUSION: These data provide strong evidence for the importance of T cells in
      inducing TNFalpha in chronic inflammatory rheumatoid tissue, and give insight
      into the mechanism whereby these T cells are activated in vivo. Furthermore, they
      indicate that production of TNFalpha in pathologic tissue is regulated
      differently from physiologic antigen-dependent TNFalpha production, which raises
      the possibility that selective inhibitors of TNFalpha in disease may be
      developed.

PMID- 11822412
TI  - [Dentistry in antiquity].
AB  - The Etruscan gold dental appliances to women of means were a remarkable start of
      the application of inserted teeth. The Romans that followed paid great attention
      to the dental system and the poet Martialis is one of the first Roman writers who
      speaks clearly of artificial teeth. Celcus, with his medical writings in eminent
      Latin, made a nice contribution to dental surgery and some of the prescriptions
      and remedies of Scribonius Largus were fairly effectual. Dioskorides distributed
      a most comprehensive pharmacological guide presenting a great number of medical
      applications - some related to teeth and gums. Plinius collected a celebrated
      encyclopaedia on medicine and natural science crammed with all sort of facts -
      some absurd. The passages concerning teeth and gums has thus got a miscellaneous
      description of current folklore and more reliable treatments. Galenos, after
      Hippocrates the greatest physician of ancient times, was a prolific writer. He
      produced medical reference books covering all medical branches that became
      authoritative for nearly two thousand years and the portions of dental treatments
      are detailed. The Romans had a widespread interest of mouth-care with toothpicks,
      mouthwashes, pain relieving remedies, the use of instruments and in some cases
      constructions of false teeth - but no real explanation of caries.

PMID- 11822413
TI  - Robert Tigerstedt, scientist, teacher and critic.

PMID- 11822414
TI  - 2002 Nutrition Week. February 23-27, 2002. San Diego, California, USA. Abstracts.

PMID- 11822415
TI  - The influence of spaceflight on Chlorella.
AB  - Three strains of Chlorella were investigated following spaceflight aboard Zond-5.
      Synchronized suspensions of Chlorella cells were grown in special containers.
      Each of these contained 0.1 X 10(6) cells. In the laboratory the strains LARG-1
      and LARG-3 were examined microscopically. Nearly all the cells were in an
      autospore stage (94-98% for LARG-1 and 96-98% for LARG-3). Space effects on
      survival, mutation and cell development were studied. During the study of cell
      sporulation dynamics, the number of autospores resulting from the first
      sporulation was estimated. Percentage survival of the exposed cells is lower than
      that of the control. In the experimental material development of cells has been
      delayed and the percentage of visible mutations has been increased.

PMID- 11822416
TI  - Radiobiological studies of plants orbited in Biosatellite II.
AB  - The Biosatellite II Tradescantia experiment probed the effects of the space
      environment on spontaneous and radiation-induced mutation rates and on
      cytological changes in Tradescantia clone 02. Thirty two young flowering plants
      arranged in a plastic housing with the roots immersed in nutrient solution were
      exposed to gamma radiation from an on-board 85 Strontium source during the two
      day orbital flight. Unirradiated plants were flown in a package in the spacecraft
      behind a tungsten radiation shield and identical non-flight control packages
      (with and without irradiation) were maintained at the launch site. After
      retrieval of the spacecraft near Hawaii, samples of root tip, ovary and stamen
      tissues were collected. These and the intact plants were flown to the Brookhaven
      National Laboratory for observations on the following end points: somatic
      mutation, cell size, loss of reproductive integrity resulting in stunted stamen
      hairs, pollen grain mortality, frequency of micronuclei in pollen, disturbed
      mitotic spindle function and chromosome aberrations. Analysis of data on somatic
      mutation, cell size and chromosome aberration end points showed no significant
      differences between flight and non-flight samples. However, pollen abortion,
      frequency of micronuclei in pollen and loss of reproductive integrity (stamen
      hair stunting) showed increases associated with weightlessness in irradiated
      material. Root tip and microspore cells showed effects of disturbed mitotic
      spindle function in orbited plants both with and without irradiation. Clearly
      differences exist between flight and non-flight material and the significance and
      possible mechanisms for these effects are being studied in continuing non-flight
      tests.

PMID- 11822417
TI  - Abstracts of the Society of Surgical Oncology 55th Annual Cancer Symposium.
      Denver, Colorado, USA. March 14-17, 2002.

PMID- 11822418
TI  - Accepting the consequences of a treatment-refusal decision.

PMID- 11822419
TI  - Citizens' rights and the new technologies: a European challenge.

PMID- 11822420
TI  - The weakness of the intention to be uncontroversial on controversial issues.

PMID- 11822421
TI  - Comments on the "Report of the European Group on Ethics in Science and New
      Technologies".

PMID- 11822422
TI  - Fundamental rights and biotechnology.

PMID- 11822423
TI  - Global bioethics with humility and responsibility.

PMID- 11822424
TI  - The development of new monometallic bifunctional catalysts with Lewis acid and
      Lewis base properties, and their application in asymmetric cyanation reactions.
AB  - Bifunctional catalysts can drastically improve the efficiency of asymmetric
      processes with respect to enantioselectivity and/or conversion rate. A new type
      of chiral bifunctional catalyst has been developed recently in the Shibasaki
      group that contains both Lewis acid and Lewis base moieties. These monometallic
      and bifunctional phosphinoyl-containing catalysts are able to coordinate both
      nucleophilic and electrophilic substrates in the transition state. Several
      successful applications of this new catalytic concept in the field of asymmetric
      cyanation reactions have already been reported, for example, the asymmetric
      hydrocyanation of aldehydes and imines as well as the asymmetric Reissert
      reaction. The development and principle of this catalytic concept as well as main
      applications thereof are reviewed in this article.

PMID- 11822425
TI  - Metallo-Supramolecular initiators for the preparation of novel functional
      architectures.
AB  - Polymeric materials containing coordinative units have become a field of
      increasing interest. The combination of inorganic metal-containing units and
      macromolecules leads to supramolecular structures with new properties. One
      promising approach to such systems is the application of metallo-supramolecular
      initiators for living and controlled polymerization methods. The utilization of
      bi- and terpyridine units and complexes for this purpose will be discussed in
      this article.

PMID- 11822426
TI  - High-Relaxivity contrast agents for magnetic resonance imaging based on multisite
      interactions between a beta-cyclodextrin oligomer and suitably functionalized
      GdIII chelates.
AB  - The results reported in this work show that tightly assembled adducts formed by
      trisubstituted GdIII complexes and a beta-CD multimer (Poly-beta-CD, d.p. ca. 12)
      may represent very interesting candidates for novel MRI applications wherein a
      high number of paramagnetic ions endowed with high relaxivity (per GdIII ion) are
      necessary. The relaxivities found for the paramagnetic adducts represent a
      remarkable step forward on the relaxivity scale. However, a detailed
      investigation of the determinants of the relaxation enhancement in these systems
      shows that their relaxivities are still limited by a nonoptimal tauR and a
      relatively long exchange lifetime of the coordinated water(s). Moreover, the
      exchange rate of the water molecule(s) coordinated to the GdIII ion further
      decreases upon binding to the Poly-beta-CD. It is suggested that this finding is
      related to the structural properties of the supramolecule, which brings a high
      density of hydroxyl groups into the proximity of the "guest" complexes, and this
      yields an overall reinforcement of the hydrogen-bonding network involving the
      coordinated water(s). On the other hand, such a tight arrangement appears
      responsible for an enhanced contribution to the observed relaxivity arising from
      water molecules in the second coordination sphere of the metal center.

PMID- 11822428
TI  - The closo-[Sn9M(CO)314- Zintl ion clusters where M = Cr, Mo, W: two structural
      isomers and their dynamic behavior.
AB  - The closo-[Sn9M(CO)3]4-ions where M = Cr (1), Mo (2), W (3) were prepared from
      [LM(CO)3] precursors (L=mesitylene, cycloheptatriene), K4Sn9. and 2,2,2-cryptand
      in ethylenediamine/toluene solvent mixtures. The [K(2,2,2-cryptand)]+ salts are
      very air and moisture sensitive and have been characterized by IR, 119Sn, and 13C
      NMR spectroscopy and single-crystal X-ray diffraction studies. Complexes 1-3 form
      bicapped square-antiprismatic 10-vertex 22-electron closo structures in which the
      [M(CO)3] units occupy cluster vertices. For 1 and 2, the clusters have C4.
      symmetry in the solid state in which the [M(CO)A] fragments occupy capping
      positions with Sn9(4-) ions that are bound to the metal in an 4 fashion. For 3,
      the [M(CO)3] fragment occupies a position in the square plane with an eta/5-Sn9(4
      ) ion and C(s) point symmetry. For 1-3, a dynamic equilibrium exists between the
      eta4 and eta5 structures yielding three 119Sn NMR signals that reflect the three
      chemically distinct Sn environments of the higher symmetry C(4v) structure. The
      119Sn NMR chemical shifts and coupling constants show solvent and temperature
      dependencies due to the equilibrium process. A triangular-face rotation mechanism
      is proposed to describe the dynamic behavior.

PMID- 11822427
TI  - A hydrogen-bonding receptor that binds cationic monosaccharides with high
      affinity in methanol.
AB  - A dicarboxylate host (1) binds cationic monosaccharides such as D-glucosamine HCl
      (2), D-galactosamine-HCl (3), and D-mannosamine-HCl (4) with high affinity (K1 =
      8.0 x 10(4)-2.0 x 10(5) M(-1)) in methanol. In circular dichroism (CD)
      spectroscopy a positive exciton-coupling band was observed near 290 nm; this
      indicates that the saccharides are recognized by multiple point interactions.
      Since the corresponding neutral monosaccharides are not significantly bound, one
      may conclude that complex formation is primarily due to the electrostatic
      interaction between NH3+ in the guest and one carboxylate in the host and
      secondarily due to hydrogen-bonding interactions of OH groups with the other
      carboxylate and/or nitrogen bases. Molar ratio plots and Job plots indicate that
      host 1 and cationic monosaccharide guests form CD-active, pseudo-cyclic 1:1
      complexes at low guest concentration followed by the formation of CD-silent,
      acyclic 1:2 1-saccharide complexes at high guest concentration. The possible
      binding modes are discussed in detail on the basis of molecular mechanics
      calculations and chemical shift changes in 1H NMR spectra. The results of
      competition experiments with several cationic reference compounds bearing fewer
      OH groups than 2-4 are consistent with the proposed binding model. Thus, the
      present study is a rare example of saccharide recognition in a protic solvent,
      where in general, hydrogen-bonding interactions are rarely useful because of
      strong solvation energy. These are apparently the strongest saccharide complexes
      involving noncovalent interactions between host and guest. We believe that the
      findings are significant as a milestone toward development of new saccharide
      recognition systems ultimately useful in aqueous solution.

PMID- 11822429
TI  - Total synthesis of (-)-salicylihalamide.
AB  - A concise total synthesis of the potent cytotoxic marine natural products
      salicylihalamide A and B (la, b) is reported. Key steps of our approach were the
      asymmetric hydrogenation reactions of beta-keto esters 18 and 32 catalyzed by
      [((S)-BINAP)Ru-Cl2]2. NEt3 and the cyclization of the macrolide core by ring
      closing olefin metathesis (RCM) using the "second-generation" ruthenium carbene
      complex 24 as the catalyst which bears an imidazol-2-ylidene ligand. The EIZ
      ratio obtained in this macrocyclization reaction was determined by the protecting
      groups at the remote phenolic OH group of the cyclization precursor. The
      elaboration of the resulting cycloalkene 37 into the final target involved a
      CrCl2-mediated synthesis of vinyliodide 49 which, after deprotection, did undergo
      a copper-catalyzed cross-coupling process with the (Z,Z)-configurated carboxamide
      42 to form the labile enamide moiety of 1. Compound 42 was derived from a
      palladium-catalyzed Negishi coupling between butynylzinc chloride and 3
      iodoacrylate 39 followed by a Lindlar reduction of enyne 40 thus obtained and a
      final aminolysis of the ester group.

PMID- 11822430
TI  - Alkyne metathesis: development of a novel molybdenum-based catalyst system and
      its application to the total synthesis of epothilone A and C.
AB  - Sterically hindered molybdenum(III) amido complexes of the general type
      [Mo[(tBu)(Ar)N]3] (1), upon treatment with CH2Cl2 or other halogen donors, have
      been converted into highly effective catalysts for all kinds of alkyne metathesis
      reactions. Although the actual nature of the propagating species formed in situ
      is still elusive, halogen transfer to the Mo center of 1 plays a decisive role in
      the activation of such precatalysts. It was possible to isolate and characterize
      by X-ray crystallography some of the resulting molybdenum halide derivatives such
      as 15, 16 and 20 which themselves were shown to be catalytically active. Numerous
      applications illustrate the performance of the catalytic system 1/CH2Cl2 which
      operates under mild conditions and tolerates an array of polar functional groups.
      The wide scope allows the method to be implemented into the total synthesis of
      sensitive and polyfunctional natural products. Most notable among them is a
      concise entry into the potent anticancer agents epothilone A (86) and C (88). The
      macrolide core of these targets is forged by ring closing alkyne metathesis
      (RCAM) of diyne 113, followed by Lindlar hydrogenation of cycloalkyne 114 thus
      formed. Since this strategy opens a stereoselective entry into (Z)-alkene 115,
      the approach is inherently more efficient than previous syntheses based on
      conventional RCM.

PMID- 11822431
TI  - Efficient synthesis of highly functionalized indazoles and 2,3-dihydro-1,2
      benzisoxazoles by reaction of stable Fischer dienyl carbenes and isocyanides.
AB  - A range of stable chromium and tungsten Fischer dienyl carbenes have been
      prepared by [3+2] cycloaddition of alkenylethynyl carbene complexes with nitrones
      or diazoalkanes. Treatment of these systems with isocyanides gives entry to
      highly functionalized 2,3-dihydro-1,2-benzisoxazoles and indazoles in a
      completely regioselective fashion, under mild conditions, and with high yields.
      This methodology can be also applied to the preparation of analogous
      naphthoisoxazoles starting from arylethynyl Fischer complexes. Reductive cleavage
      of the isoxazole moiety in the prepared heterocycles also enables the efficient
      synthesis of highly substituted p-aminophenols.

PMID- 11822432
TI  - Density functional investigation of reactive intermediates derived from alkyne
      Co2(CO)6 complexes.
AB  - By applying the hybrid density functional method B3LYP and a flexible all
      electron basis set, structures and energies of reactive intermediates derived
      from the 1-butyne complex of Co2(CO), (1) were calculated. In particular, the
      geometry, electronic distribution, and configurational stability of the cationic,
      radical, and anionic Co2(CO)6-complexed propargylic species were studied. The
      calculations revealed that the configurational barrier, that is, the racemization
      barrier for the antarafacial migration of the CHCH3 group, is low (7.6 kcalmol(
      1)) for the radical and is similar to the experimental value for the
      corresponding cation (ca. 10 kcalmol(-1)). However, a high racemization barrier
      (23.7 kcalmol(-1)) for the anionic intermediate suggests the possibility of
      stereospecific reactions involving Co2(CO)6-complexed propargylic anions.

PMID- 11822433
TI  - Metallophilic interactions in closed-shell copper(I) compounds--a theoretical
      study.
AB  - Cuprophilic interactions in neutral perpendicular model dimers of the type
      (CH3CuX)2 (X = OH2, NH3, SH2, PH3, N2, CO, CS, CNH, CNLi) were analyzed by ab
      initio quantumchemical methods. The basis set superposition error for the weakly
      interacting CH3CuX subunits is significant and is discussed in detail. A new
      correlation-consistent pseudopotential valence basis set for Cu. derived at the
      second-order Moller-Plesset level suppresses considerably the basis set
      superposition error in Cu-Cu interactions compared to the standard Hartree-Fock
      optimized valence basis set. This allowed the first accurate predictions of
      cuprophilicity, which has been the subject of considerable debate in the past.
      The dependence of the strength of cuprophilic interactions on the nature of the
      ligand X was addressed. The Cu-Cu interaction increases with increasing sigma
      donor and pi-acceptor capability of the ligand and is approximately one-third of
      the well-documented aurophilic interactions. By fitting our potential-energy data
      to the Hershbach-Laurie equation, we determined a relation between the Cu-Cu bond
      length and the Cu-Cu force constant; this is important for future studies on
      vibrational behaviour. The role of relativistic effects on the structure and the
      interaction energy is also discussed. Finally we investigated cuprophilic
      interactions in (CH3Cu)4 as a model species for compounds isolated and
      characterized by X-ray diffraction.

PMID- 11822434
TI  - A new 1 --> infinity [Ni7] cluster in LaNi7In6 and distorted bcc indium cubes in
      LaNiIn4.
AB  - LaNiIn4 and LaNi7In, were prepared by reaction of the elements in an arc melting
      furnace and subsequent annealing at 870 K for five weeks. Both compounds were
      investigated by X-ray diffraction on powders and single crystals and the
      structures were refined from single-crystal data: Cmcm, a = 448.2(1), b =
      1689.5(4). c = 722.1(1) pm, wR2 = 0.0340, 472 F2 values, 24 variables for
      LaNiIn4, and Ibam, a = 806.6(2). b = 924.8(2). c = 1246.5(2) pm. wR2 = 0.0681.
      726 F2 values and 40 variables for LaNi7In,. LaNiIn4 adopts the YNiAl4-type
      structure. The nickel and indium atoms form a three-dimensional infinite [NiIn4]
      polyanion in which the lanthanum atoms fill distorted hexagonal channels. No Ni
      Ni contacts occur. The indium substructure consists of distorted bcc-like indium
      cubes. LaNi7In6 crystallizes with a peculiar new structure type. The nickel atoms
      build a 1 --> infinity [Ni7] cluster unit with Ni-Ni distances ranging from 249
      to 269 pm. The cluster units are enveloped by indium atoms. These larger units
      show an orthorhombic rod packing with the lanthanum atoms filling the space
      between the rods. Several nickel clusters in ternary rare earth metal nickel
      indides and the structural relations of the LaNi7In6 structure with the cubic
      NaZn13 type are discussed.

PMID- 11822435
TI  - Chemistry of porphyrin-appended cellulose strands with a helical structure:
      spectroscopy, electrochemistry, and in situ circular dichroism
      spectroelectrochemistry.
AB  - Around 100 porphyrin units have been selectively linked at C(6)-O to a cellulose
      (Avicel). The properties of the metal-free and zincated porphyrin-celluloses 2
      and Zn-2 have been determined by optical and electrochemical methods. Circular
      dichroism indicates a helical arrangement of the porphyrin units and reveals
      intra-chain coupling reminiscent, in the broadest sense, of strands of nucleic
      acids. Cyclic voltammetry and spectroelectrochemistry have been used to
      characterize the radical ions and dianions. The electrochromism of the oxidation
      of cellulose 2 to porphyrin radical cations of 2 has been employed for both
      molecular switching and the transduction of an electrochemical input into
      chiroptical signal expression.

PMID- 11822436
TI  - Total synthesis of colombiasin A and determination of its absolute configuration.
AB  - The total synthesis of the recently reported marine natural product colombiasin A
      (1) and determination of its absolute configuration are reported. Two Diels-Alder
      cycloadditions and a palladium-catalyzed rearrangement are employed as key
      reactions to construct the tetracyclic framework of the target molecule. The
      enantioselective synthesis of colombiasin A utilizes Mikami's [(S)-BINOL-TiCl2]
      catalyst to asymmetrically introduce the first chiral center during the initial
      Diels-Alder reaction and, in conjunction with X-ray crystallographic analysis of
      a bromine containing derivative, led to the assignment of the absolute
      configuration of the natural product.

PMID- 11822437
TI  - Trimerization of alkali dicyanamides M[N(CN)2] and formation of
      tricyanomelaminates M3[C6N9] (M = K, Rb) in the melt: crystal structure
      determination of three polymorphs of K[N(CN)2], two of Rb[N(CN)2], and one of
      K3[C6N9] and Rb3[C6N9] from X-ray powder diffractometry.
AB  - The alkali dicyanamides M[N(CN)2] (M=K, Rb) were synthesized through ion
      exchange, and the corresponding tricyanomelaminates M3[C6N9] were obtained by
      heating the respective dicyanamides. The thermal behavior of the dicyanamides and
      their reaction to form the tricyanomelaminates were investigated by temperature
      dependent X-ray powder diffractometry and thermoanalytical measurements.
      Potassium dicyanamide K[N(CN)2] was found to undergo four phase transitions: At
      136 degrees C the low-temperature modification alpha-K[N(CN)2] transforms to beta
      K[N(CN)2], and at 187degrees C the latter transforms to the high-temperature
      modification gamma-K[N(CN)2], which melts at 232 degrees C. Above 310 degrees C
      the dicyanamide ions [N(CN)2]- trimerize and the resulting tricyanomelaminate
      K3[C6N9] solidifies. Two modifications of rubidium dicyanamide have been
      identified: Even at -25 degrees C, the a form slowly transforms to beta
      Rb[N(CN)2] within weeks. Rb[N(CN)2] has a melting point of 190 degrees C. Above
      260 degrees C the dicyanamide ions [N(CN)2]- of the rubidium salt trimerize in
      the melt and the tricyanomelaminate Rb3[C6N9] solidifies. The crystal structures
      of all phases were determined by powder diffraction methods and were refined by
      the Rietveld method. alpha-K[N(CN)2] (Pbcm, a = 836.52(1), b = 46.90(1), c =7
      21.27(1) pm, Z = 4), gamma-K[N(CN)2] (Pnma, a = 855.40(3), b = 387.80(1),
      1252.73(4) pm, Z = 4), and Rb[N(CN)2] (C2/c, a = 1381.56(2), b = 1000.02(1), c =
      1443.28(2) pm, 116.8963(6) degrees, Z = 16) represent new structure types. The
      crystal structure of beta-K[N(CN)2] (P2(1/n), a = -726.92(1), b 1596.34(2), c =
      387.037(5) pm, 111.8782(6) degrees, Z = 4) is similar but not isotypic to the
      structure of alpha Na[N(CN)2]. alpha-Rb[N(CN)2] (Pbcm, a = 856.09(1), b =
      661.711(7), c = 765.067(9) pm, Z = 4) is isotypic with alpha-K[N(CN)2]. The
      alkali dicyanamides contain the bent planar anion [N(CN)2]- of approximate
      symmetry C2, (average bond lengths: C-N(bridge) 133, C-N(term) 113 pm; average
      angles N-C-N 170 degrees, C-N-C 120 degrees). K3[C6N9] (P2(1/c), a = 373.82(1), b
      = 1192.48(5), c = 2500.4(1) pm, beta = 101.406(3) degrees, Z = 4) and Rb,[C6N9]
      (P2(1/c), a = 389.93(2), b = 1226.06(6), c = 2547.5(1) pm, 98.741(5) degrees,
      Z=4) are isotypic and they contain the planar cyclic anion [C6N9]3-. Although
      structurally related, Na3[C6N9] is not isotypic with the tricyanomelaminates
      M3[C6N9] (M = K, Rb).

PMID- 11822438
TI  - Synthesis, spectroscopic, and structural properties of spirocyclopropanated
      bicyclobutylidenes and their radical cations.
AB  - The spirocyclopropanated bicyclobutylidenes 3-7 have been prepared by McMurry
      coupling of the corresponding spirocyclopropanated cyclobutanone (3 and 5),
      Staudinger-Pfenniger reaction (4), oxidative coupling of a Wittig ylide (4) or
      Wittig olefination of perspirocyclopropanated cyclobutanone (6 and 7). The
      structure of the parent 2a and the perspirocyclopropanated bicyclobutylidene 5
      was determined by X-ray crystallography which disclosed considerable steric
      congestion around the double bond. As a result 5 did undergo addition of
      dichlorocarbene, epoxidation with meta-chloroperbenzoic acid, and
      cyclopropanation with CH2I2/ZnEt2, but did not add the more bulky dibromocarbene.
      The reaction of 5 with tetracyanoethene proceeded smoothly, but led to a formal
      [3+2] cycloadduct across the proximal single bond of one of the inner
      cyclopropane rings. The consecutive spirocyclopropanation of bicyclobutylidene
      led to a bathochromic shift in the UV spectra of 12 and 17nm, respectively, for
      each pair of beta- and alpha-spirocyclopropane groups. In the He(I)-photoelectron
      spectra of these bicyclobutylidenes, the effect of spirocyclopropanation upon
      their pi-ionization energies (pi-IE,) was found to be almost additive, leading to
      a lowering of 0.05 eV per any additional beta-spirocyclopropane, and 0.28-0.22 eV
      per additional alpha-spirocyclopropane group; this indicates an increasing
      nucleophilicity of the double bonds in the order 1 < 4 < 3 < 5. Following the
      radical cations of the three symmetrical bicyclobutylidenes without (2a, b) and
      with six (5) spiroannelated cyclopropane rings, the radical cations of two
      symmetrical bicyclobutylidenes with two (4) and four (3) such rings were studied
      by ESR spectroscopy. Whereas 2b.+, 3.+, and 5.+ could be generated by
      electrolytic oxidation of the corresponding hydrocarbons in solution, the spectra
      of 2a.+ and 4.+, with unsubstituted 2,2',4,4'-positions, were observed upon
      radiolysis of their neutral precursors in a Freon matrix. On going from 2a.+ to
      4.+, the coupling constant [aH] of the eight beta protons in the 2,2',4,4'
      positions of bicyclobutylidene increases from 2.62 to 3.08 mT, and that of the
      four gamma protons in the 3,3'-positions changes from 0.27 to 0.049 to 0.401 mT
      on passing from 2a.+ via 2b.+ to 3.+. Computations by means of the density
      functional theory (DFT) at the B3LYP/6-311+G*//B3LYP/6-31G* level reproduce well
      the experimental hyperfine data.

PMID- 11822439
TI  - Enantioselective hydrogenations of arylalkenes mediated by [Ir(cod) (JM-Phos) ]+
      complexes.
AB  - Phosphine oxazoline ligands la-j were converted to the corresponding
      [Ir(cod)(phosphine oxazoline)]+ complexes 2a-j. X-ray diffraction analyses of
      complexes 2b, 2h, 2i, and 2j were performed. The tert-butyl-, 1,1-diphenylethyl-,
      and phenyl-oxazoline complexes (2b, 2h, and 2i, respectively) had typical square
      planar metal environments with chair-like metallocyclic rings. However, the 3,5
      di-tert-butylphenyl oxazoline complex 2j was distorted toward a tetrahedral metal
      geometry. This library of complexes was tested in asymmetric hydrogenations of
      several arylalkenes. High enantioselectivities and conversions were observed for
      some substrates. A possible special role for the HPh2C-oxazoline substituent in
      asymmetric hydrogenations was identified and is discussed. In attempts to
      rationalize why high enantioselectivities were not observed for some alkenes, a
      series of deuterium labeling experiments were performed to probe for competing
      reactions that occurred prior to the hydrogenation step. Double bond migrations
      were inferred for several substrates, and this is a significant complication in
      asymmetric hydrogenations of arylalkenes that had not been discussed prior to
      this study. A mechanistic rationale is proposed involving competing double bond
      migration for some but not all substrates. Appreciation of this complication will
      be valuable in further studies aimed at optimization of enantioselection in
      asymmetric hydrogenations of unfunctionalized alkenes.

PMID- 11822440
TI  - Reactivity of the inversely polarized phosphaalkenes RP=C(NMe2)2 (R = tBu, Me3Si,
      H) towards arylcarbene complexes [(CO)5M=C(oEt)Ar] (Ar= Ph, M = Cr, W; Ar = 2
      MeC6H4, 2-MeOC6H4, M = W).
AB  - The reaction of the arylated Fischer carbene complexes [(CO)5M=C(OEt)Ar] (Ar=Ph;
      M = Cr, W; 2-MeC6H4; 2-MeOC6H; M = W) with the phosphaalkenes RP=C(NMe2), (R=tBu,
      SiMe3) afforded the novel phosphaalkene complexes [[RP=C(OEt)Ar]M(CO)5] in
      addition to the compounds [(RP=C(NMe2)2]M(CO)5]. Only in the case of the R =
      SiMe3 (E/Z) mixtures of the metathesis products were obtained. The
      bis(dimethylamino)methylene unit of the phosphaalkene precursor was incorporated
      in olefins of the type (Me2N)2C=C(OEt)(Ar). Treatment of [(CO)5W=C(OEt)(2
      MeOC6H4)] with HP=C(NMe2)2 gave rise to the formation of an E/Z mixture of
      [[(Me2N)2CH-P=C(OEt)(2-MeOC6H4)]W(CO)5] the organophosphorus ligand of which
      formally results from a combination of the carbene ligand and the phosphanediyl
      [P-CH(NMe2)2]. The reactions reported here strongly depend on an inverse
      distribution of alpha-electron density in the phosphaalkene precursors (Pdelta
      Cdelta+), which renders these molecules powerfu] nucleophiles.

PMID- 11822441
TI  - Comproportionation reaction and hindered rotation of coordinated pyridine rings
      in an acetate-bridged tetraplatinum(II) cluster with pyridine-based ligands in
      the cluster plane.
AB  - A series of pyridine-substituted derivatives of octaacetatotetraplatinum(II),
      [Pt4(CH3COO)8-n(L)2n]n+ (L= 4-dimethylaminopyridine (dmap), pyridine (py), 4
      cyanopyridine (cpy); n = 1-4) were prepared, and the tetra- and octasubstituted
      forms (n = 2 and 4) were isolated. 1HNMR spectra showed that this type of cluster
      undergoes a comproportionation reaction. Reactions between clusters in which n =
      0 and 2, n = 0 and 4, and n = 2 and 4 afforded Pt4 clusters with n = 1, 2, and 3,
      respectively, as a main product in acetonitrile. The dmap-substituted clusters,
      trans-[Pt4(CH3COO)6(dmap)4](ClO4)2 x 3CH3NO2 (3a(ClO4)2 x 3CH3NO2) and
      [Pt4(CH3COO)4(dmap)8](ClO4)4 x 4 H2O (5a(ClO4)4-4H2O), have been structurally
      characterized. Both 3a and 5a have a square-planar cluster core comprised of four
      PtII ions, and all eight out-of-plane coordination sites are occupied by acetate
      ligands in a bridging mode. In 5a, all of the in-plane sites are occupied by dmap
      ligands. In 3a, four dmap ligands occupy the coordination sites at the two
      mutually opposite edges of the square planar cluster skeleton, giving a trans
      tetrasubstituted form of [Pt4(CH3COO)8-] (1). In octasubstituted 5a, adjacent
      dmap ligands are so closely arranged that the Pt-N distances (2.20(3), 2.30(3) A)
      are longer than those in tetrasubstituted 3a (2.13(1), 2.15(1) A) and related Pt4
      clusters. Furthermore, rotation of the dmap ligand about the Pt-N bond in 5a was
      restricted, and the rate constant of the rotation was 4.5s(-1) at 20 degrees C
      from dynamic NMR study. Cluster [Pt4(CH3COO)5(dmap)6]3+ (4a) also exhibited
      similar hindered rotation with the rate constants of 2.0s(-1), 12s(-1) and
      approximately 10(4)s(-1) at 20 degrees C depending on the coordination sites of
      the dmap ligands in 4a.

PMID- 11822442
TI  - Postulation of the mechanism of the selective synthesis of isotactic poly(methyl
      methacrylate) catalysed by [Zr[(Cp)(Ind)CMe2](Me)(thf)](BPh4): a Hartree-Fock,
      MP2 and density functional study.
AB  - The bridged. C1-symmetric, single-component zirconocene
      [Zr((Cp)(Ind)CMe2](Me)(thf)](BPh4) (Ind = indenyl, Cp = cyclopentadienyl)
      polymerises methyl methacrylate (MMA) selectively to isotactic poly(methyl
      methacrylate) (PMMA) without further cocatalysts or activators. To elucidate the
      stereoselective steps of the polymerisation of MMA by using this catalyst we
      studied the propagation steps occurring with the derivative [Zr[(Cp)(Ind)CH2][-O
      C(OMe)=C(Me)(Et)](MMA)]+ by ab initio calculations at the Hartree-Fock(HF) level
      of theory. After the initiation step, which consumes the first two MMA molecules,
      each new catalytic cycle begins with the stereoselective addition of a new MMA
      molecule at the indenyl side of the zirconocene fragment. At the same time the
      enolate ring undergoes a stereoselective in-plane ring shift to the side opposite
      to the indenyl ring. These findings are used to postulate a mechanism for the
      polymerisation that explains the stereoselective synthesis of isotactic PMMA.

PMID- 11822443
TI  - Redox-switchable direction of photoinduced electron transfer in an Ru(bpy)3(2+)
      viologen dyad.
AB  - Quenching of the 3MLCT excited state of [Ru(bpy)3]2+ (bpy=bipyridine) by the
      reduction products (MV*+ and MV0) of methyl viologen (MV2+) was studied by a
      combination of electrochemistry with laser flash photolysis or femtosecond pump
      probe spectroscopy. Both for the bimolecular reactions and for the reactions in
      an Ru(bpy)3(2+)-MVn+ dyad, quenching by MV*+ and MV0 is reductive and gives the
      reduced ruthenium complex [Ru(bpy)3]+, in contrast to the oxidative quenching by
      MV2+. Rate constants of quenching (kq), and thermal charge recombination (krec)
      and cage escape yields (phi(ce)) were determined for the bimolecular reactions,
      and rates of forward (kf) and backward (kb) electron transfer in the dyad were
      measured for quenching by MV2+, MV*+, and MV0. The reactions in the dyad are very
      rapid, with values up to kf = 1.3 x 10(12) s(-1) for *Ru(bpy)3(2+)-MV*+. In
      addition, a long-lived (tau = 15 ps) vibrationally excited state of MV*+ with a
      characteristically structured absorption spectrum was detected; this was
      generated by direct excitation of the MV*+ moiety both at 460 and 600 nm. The
      results show that the direction of photoinduced electron transfer in a Ru(bpy)3
      MV molecule can be switched by an externally applied bias.

PMID- 11822444
TI  - Conformationally stable and constrained macrocarbocyclic pseudopeptide mimics of
      beta-hairpin structures.
AB  - Subjecting a D-Pro-L-Pro template harboring N- and C-terminal omega-alkenyl amino
      acids to a ring-closure metathesis reaction afforded the corresponding
      macrocyclic alkenes. A cis-alkene analogue crystallized with one molecule each of
      water and chloroform, which were retained even after heating at 100 degrees C. By
      using the reduced macrocyclic product as a template, the metathesis could be
      repeated twice on newly installed omega-alkenyl amino acids to give three-tiered
      macrocarbocyclic pseudopeptides as mixtures of conformers. NMR studies revealed
      the high conformational stability of these motifs.

PMID- 11822446
TI  - Redox-responsive molecular switches based on azoterpyridine-bridged Ru/Os
      complexes.
AB  - Three new terpyridine-based dinuclear complexes, [(tpy)Ru(azotpy)Ru(tpy)]4+ (tpy
      = 2,2':6',2''-terpyridine, azotpy = bis[2,6-bis(2-pyridyl)-4-pyridyl]diazene),
      [(tpy)Os(azotpy)Os(tpy)]4+, and [(tpy)Ru(azotpy)Os(tpy)]4+ were prepared and
      their electrochemical and photophysical properties investigated. The bridging
      ligand, azotpy, in these complexes is reduced at less negative potentials than
      the unsubstituted tpy ligand. These complexes exhibit absorption bands due to the
      metal-to-ligand charge-transfer transitions both to the unsubstituted tpy ligand
      and the bridging azotpy ligand, the latter absorption being observed at the lower
      energy side of the former. These observations are consistent with the lower lying
      pi* level of the azotpy ligand than that of the tpy ligand. These complexes are
      nonluminescent, since the excited electron is trapped in this lower lying pi*
      level of the azotpy ligand in the excited state. Reduction of this bridging
      ligand by constant potential electrolysis renders the shape of absorption spectra
      for these complexes nearly identical to those of the parent complexes,
      [M(tpy)2]2+ (M = Ru, Os). In this reduced state, the homodinuclear Os complex
      becomes luminescent at room temperature, whereas the homodinuclear Ru complex
      becomes luminescent at 77 K, thus establishing their photoswitching behavior. The
      reduced heterodinuclear complex exhibits luminescence from the Os center, which
      is sensitized by the Ru center in the same molecule as evidenced by the
      excitation spectra. Thus, the intramolecular energy transfer can be switched on
      and off by the redox reaction of the bridging component.

PMID- 11822445
TI  - Rebek imides and their adenine complexes: preferences for Hoogsteen binding in
      the solid state and in solution.
AB  - Rebek imides (3), formed from Kemp's triacid, were developed in the mid-1980's as
      model receptors for adenine derivatives. We report here the first account of
      their hydrogen-bonding preferences upon binding 9-ethyladenine (1a) in the solid
      state. Structural analysis begins with simple imides 3a-e that form discrete
      dimers, while bis-imide 4 forms ribbon-like structures in the crystalline phase.
      The hydrogen-bonding interface within each of the representative assemblies
      features short intermolecular N(3)imide...O(8*)imide* distances (ca. 2.95 A),
      indicative of two-point hydrogen bonding. Imides 3f-h could be co-crystallized
      with 1a; single-crystal X-ray analysis of the resulting complexes reveals
      hydrogen-bonding geometries nearly identical to those observed in nucleobase
      complexes of adenine and pyrimidine derivatives. Imides 3f and 3g form 2:1
      ternary assemblies with 1a; the complex of the former, (3f)2 x 1a, displays both
      Watson-Crick- and Hoogsteen-type hydrogen bonding, whereas the complex of the
      latter, (3g)2 x 1a, shows the Hoogsteen motif and imide hydrogen bonding to N(3)
      of the purine base (N(3)adenine...N(3'')imide = 3.07(1) A). Imide 3h forms a 1:1
      complex with 1a (3h x 1a x CHCl3) and displays Hoogsteen binding exclusively. All
      of the 3 x 1a assemblies show C(adenine)...O(imide) distances (3.38-3.75 A) that
      are consistent with C-H...O hydrogen bonding. Base-pairing preferences for the
      Rebek imides are further explored in solution by 1H NMR one-dimensional NOE
      experiments and by computational means; in all cases the Hoogsteen motif is
      modestly favored relative to its Watson-Crick counterpart.

PMID- 11822447
TI  - Electronic energy transfer and collection in luminescent molecular rods
      containing ruthenium(II) and osmium(II) 2,2':6',2"-terpyridine complexes linked
      by thiophene-2,5-diyl spacers.
AB  - The electronic absorption spectra, luminescence spectra and lifetimes (in MeCN at
      room temperature and in frozen n-C3H7CN at 77 K), and electrochemical potentials
      (in MeCN) of the novel dinuclear [(tpy)Ru(3)Os(tpy)]4+ and trinuclear
      [(tpy)Ru(3)Os(3)Ru(tpy)]6- complexes (3 = 2,5-bis(2,2':6',2''-terpyridin-4
      yl)thiophene) have been obtained and are compared with those of model mononuclear
      complexes and homometallic [(tpy)Ru(3)Ru(tpy)]4+, [(tpy)Os(3)Os(tpy)]4+ and
      [(tpy)Ru(3)Ru(3)Ru(tpy)]6+ Complexes. The bridging ligand 3 is nearly planar in
      the complexes, as seen from a preliminary X-ray determination of
      [(tpy)Ru(3)Ru(tpy)][PF6]4, and confers a high degree of rigidity upon the
      polynuclear species. The trinuclear species are rod-shaped with a distance of
      about 3 nm between the terminal metal centres. For the polynuclear complexes, the
      spectroscopic and electrochemical data are in accord with a significant
      intermetal interaction. All of the complexes are luminescent (phi in the range
      10(-4)-10(-2) and tau in the range 6-340 ns, at room temperature), and ruthenium-
      or osmium-based luminescence properties can be identified. Due to the excited
      state properties of the various components and to the geometric and electronic
      properties of the bridge, Ru --> Os directional transfer of excitation energy
      takes place in the complexes [(tpy)Ru(3)Os(tpy)]4+ (end-to-end) and
      [(tpy)Ru(3)Os(3)Ru(tpy)]6+ (periphery-to-centre). With respect to the
      homometallic case, for [(tpy)Ru(3)Os(3)Ru(tpy)]6+ excitation trapping at the
      central position is accompanied by a fivefold enhancement of luminescence
      intensity.

PMID- 11822448
TI  - [FeCp]+-induced hexafunctionalization of hexamethylbenzene with dendrons for the
      direct synthesis of redox-active iron-centered metallodendrimers.
AB  - Phenol tri- and nonaallyl dendrons (3 and 7, respectively) were functionalized at
      the focal position to give the new triallyl dendrons 4 and 6 and the nonaallyl
      dendrons 11 and 13 that contain a iodoalkyl or a bromobenzyl termini. All these
      dendrons were used for the [FeCp]+-induced hexafunctionalization of
      hexamethylbenzene in [FeCp(eta6-C6Me6)][PF6] (1) under mild conditions in the
      presence of KOH. These reactions directly yielded the 18-allyl and 54-allyl
      dendrimers 9, 10, and 14 with a [FeCp(eta6-arene)]+ unit located at the dendrimer
      core. Cyclic voltammetry studies were recorded in THF and DMF with these
      metallodendrimers and compared with those of analogous dendrimers or complexes of
      smaller size that contain a [FeCp(eta6-arene)]+ unit at the core. The decreased
      rate of heterogeneous electron transfer when the dendritic size increases first
      disclosed by Diederich and Gross is confirmed. The variation of the redox
      potential of the Fe(II/I) redox system with increasing dendritic size is
      negligible even in a solvent of high dielectric constant such as DMF. This trend
      is attributed to fact that the involved "redox" orbital is buried on the metal
      center, well protected by the shell of alkyl chains (electron-reservoir nature),
      unlike in ferrocene. The chemical irreversibility increases in THF as the
      dendrimer size increases, due to more facile ligand substitution with THF at the
      19-electron level when the chain bulk increases.

PMID- 11822449
TI  - On the mechanism of the copper-catalyzed cyclopropanation reaction.
AB  - The selectivity-determining step in enantioselective copper-catalyzed
      cyclopropanation with diazo compounds has been studied by experimental and
      computational methods. The addition of the very reactive metallacarbene
      intermediate in an early transition state to the substrate alkene is concerted
      but strongly asynchronous, with substantial cationic character on one alkene
      carbon in the neighborhood of the transition state. Evidence from isotope effects
      and Hammett studies supports the nature of the transition state. Formation of a
      metallacyclobutane intermediate by a [2+2] addition is kinetically disfavored.
      Ligand-substrate interactions influencing the enantio- and diastereoselectivity
      have been identified, and the preferred orientation of the alkene substrate
      during the addition is suggested.

PMID- 11822450
TI  - Ordered arrays of II/VI diluted magnetic semiconductor quantum wires: formation
      within mesoporous MCM-41 silica.
AB  - We present a novel way of synthesising highly ordered arrays of hollow Cd(1
      x)Mn(x)S quantum wires with lateral dimensions of 3-4 nm separated by 1-2 nm SiO2
      barriers by forming Cd(1-x)Mn(x)S (0 < or = x < or = 1) semiconductors inside the
      pore system of mesoporous MCM-41 SiO2 host structures. X-ray diffraction and
      transmission electron microscopy (TEM) studies reveal the hexagonal symmetry of
      these arrays (space group p6m) and confirm the high degree of order.
      Physisorption measurements show the filling of the pores of the MCM-41 SiO2. The
      X-ray absorption near-edge structure (XANES), extended X-ray absorption fine
      structure (EXAFS), electron paramagentic resonance (EPR), and Raman studies
      confirm the good crystalline quality of the incorporated (Cd,Mn)S guest. The
      effects of reducing the lateral dimensions on the magnetic and electronic
      properties of the diluted magnetic semiconductor were studied by
      photoluminescence (PL) and PL excitation spectroscopy and by SQUID and EPR
      measurements in the temperature range 2-400 K. Due to the quantum confinement of
      the excitons in the wires, an increase of about 200 meV in the direct band gap
      was observed. In addition, the p-d hybridisation-related bowing of the band gap
      as a function of Mn concentration in the wires is much stronger than in the bulk.
      This effect is related to the increase in the band gap due to quantum
      confinement, which shifts the p-like valence band edge closer to the 3d-related
      states of Mn in the valence band. Thus, the p-d hybridisation and the strength of
      the band gap bowing are increased. Compared to bulk (II,Mn)VI compounds,
      antiferromagnetic coupling between the magnetic moments of the Mn2+ ions is
      weaker. For the samples with high Mn concentrations (x > 0.8) this leads to a
      suppression of the phase transition of the Mn system from paramagnetic to
      antiferromagnetic. This effect can be explained by the fact that the lateral
      dimensions of the wires are smaller than the magnetic length scale of the
      antiferromagnetic ordering.

PMID- 11822451
TI  - Intramolecular carbolithiation reactions of chiral alpha-amino-organolithium
      species.
AB  - Enantiomerically enriched alpha-amino-organolithium species, in which the lithium
      atom is attached to a stereogenic carbon centre, have been found to be chemically
      stable at room temperature in a solvent of very low polarity and undergo
      intramolecular carbolithiation onto an unactivated alkene. The configurational
      stability of the chiral organolithium species, bearing a variety of N-alkenyl
      substituents, was probed by studying the enantiomeric purity of the cyclization
      products. With N-but-3-enyl-2-lithiopyrrolidine, cyclization to the five-membered
      ring is more rapid than racemization and a high yield of the pyrrolizidine
      alkaloid (+)-pseudoheliotridane was obtained with no loss of optical purity. In
      contrast, with N-pent-4-enyl-2-lithiopyrrolidine, cyclization to the six-membered
      ring was found to occur with significant loss of optical purity. The cyclization
      to the six-membered ring was determined to occur with a half-life, t(1/2)
      approximately 90 min at 23 degrees C. The epimerization of this organolithium
      species in hexane/Et2O 4:1 was calculated to have a half-life, t(1/2)
      approximately 30 min at 23 degrees C. Enhanced levels of enantioselectivity for
      the formation of the indolizidine ring system were obtained using an alkene
      bearing a terminal phenylthio substituent. With N-[(3-phenylthio)-prop-2-enyl]-2
      lithiopyrrolidine, cyclization to the four-membered ring occurs with poor
      enantioselectivity at low temperature in THF but is highly enantioselective at
      room temperature in a solvent of very low polarity.

PMID- 11822452
TI  - Stereoselective synthesis of heterocyclic cage compounds by domino conjugate
      additions.
AB  - Heterocyclic cage compounds have been stereoselectively synthesized from
      enantiopure [(S)R]-[(p-tolylsulfinyl)methyl]-p-quinols or their amine analogues
      and 2-(trimethylsilyloxy)furan in the presence of Bu4NF. The method is
      particularly valuable not only because of the stereochemical control but also
      because the reactions occur in an experimentally simple one-pot procedure through
      a domino sequence of three consecutive conjugate additions. The intermediate 1,4
      adducts could be isolated when the reaction was carried out in the presence of
      BF3 x OEt2.

PMID- 11822453
TI  - The thermal decomposition of thiirane: a mechanistic study by ab initio MO
      theory.
AB  - Using high-level ab initio MO methods, we have identified two reaction pathways
      with different thermodynamic and kinetic properties for the thermal decomposition
      of the three-membered heterocycle thiirane (C2H4S) and related derivatives. A
      homolytic ring opening, followed by attack of the generated diradical on another
      thiirane molecule, and subsequent elimination of ethene in a fast radical chain
      reaction results in the formation of disulfur molecules in their triplet ground
      state (3S2) and requires activation enthalpies of deltaH#(298) = 222 kJ mol(-1)
      and deltaG#(298) = 212 kJ mol(-1). This reaction mechanism would result in a
      first-order rate law in agreement with one reported gas-phase experiment but does
      neither match the experimental activation energy nor does it explain the observed
      retention of the stereochemical configuration in the thermal decomposition of
      certain substituted thiiranes. Alternatively, sulfur atoms can be transferred
      from one thiirane moleculeto another with the intermediate formation of thiirane
      1-sulfide (C2H4S2). This molecule can either decompose unimolecularly to ethene
      and disulfur in its excited singlet state (1S2) or, by means of spin crossover,
      S2 in its triplet ground state may be formed. On the other hand, the thiirane 1
      sulfide may react with itself and transfer one sulfur atom from one molecule to
      another with formation of thiirane 1,1-disulfide (C2H4S3), which is an analogue
      of thiirane sulfone; thiirane is formed as the second product. The 1,1-disulfide
      may then decompose to ethene and S3. In still another bimolecular reaction, the
      thiirane 1-sulfide may react with itself in a strongly exothermic reaction to
      give S4 and two equivalents of ethene. This series of reactions results in a
      second-order rate law and requires activation enthalpies of deltaH#(298) = 109 kJ
      mol(-1) and deltaG#(298) = 144 kJ mol(-1) for the formation of thiirane 1
      sulfide, while the consecutive reactions require less activation enthalpy.
      Elemental sulfur (S8) is eventually formed by oligomerization of either S2, S3,
      or S4 in spin-allowed reactions. These findings are in agreement with most
      experimental data on the thermal desulfurization of thiirane and its substituted
      derivatives. Thiirane 1-persulfide (C2H4S3) with a linear arrangement of the
      three sulfur atoms as well as zwitterions and radicals derived from thiirane are
      not likely to be intermediates in the thermal decomposition of episulfides.

PMID- 11822454
TI  - Highly efficient antibody-catalyzed deuteration of carbonyl compounds.
AB  - Antibody 38C2 efficiently catalyzes deuterium-exchange reactions at the alpha
      position of a variety of ketones and aldehydes, including substrates that have a
      variety of sensitive functional groups. In addition to the regio- and
      chemoselectivity of these reactions, the catalytic rates (kcat) and rate
      enhancement values (kcat/kun) are among the highest values ever observed with
      catalytic antibodies. Comparison of the substrate range of the catalytic antibody
      with highly evolved aldolase enzymes, such as rabbit-muscle aldolase, highlights
      the much broader practical scope of the antibody, which accepts a wide range of
      substrates. The hydrogen-exchange reaction was used for calibration and mapping
      of the antibody active site. Isotope-exchange experiments with cycloheptanone
      reveal that the formation of the Schiff base species (as concluded from the
      16O/18O exchange rate at the carbonyl oxygen) is much faster than the formation
      of the enamine intermediate (as concluded from the H/D exchange rate), and both
      steps are faster than the antibody-catalyzed aldol addition reaction.

PMID- 11822455
TI  - Total synthesis of calditol: structural clarification of this typical component
      of Archaea order Sulfolobales.
AB  - The original structure of calditol--that is, an open-chain branched nonitol--has
      recently been questioned by various research groups and cyclopentane-based
      structures have been proposed. To unambiguously clear up this confusion, four
      isomeric cyclopentane candidates 26-29 have been synthesized. Of these, compound
      27 was found to be fully identical to the natural product present in Sulfolobus
      solfataricus (A.T.C.C. 49155). The synthesis of 27 uses a samarium-diiodide
      induced pinacolization reaction of the ketoaldehyde 15 as the critical step.

PMID- 11822456
TI  - Tuning the activity of catechol oxidase model complexes by geometric changes of
      the dicopper core.
AB  - Dicopper(II) complexes of a series of different pyrazolate-based dinucleating
      ligands [L1](-)-[L4](-) have been synthesized and characterized structurally and
      spectroscopically. A major difference between the four complexes is the
      individual metal-metal separation that is enforced by the chelating side arms of
      the pyrazolate ligand scaffold: it varies from 3.45 A in 2 x (BF4)4 to 4.53 A in
      4 x (ClO4)2. All complexes have been evaluated as model systems for the catechol
      oxidase enzyme by using 3,5-di-tert-butylcatechole (DTBC) as the test substrate.
      They were shown to exhibit very different catecholase activities ranging from
      very efficient to poor catalysts (k(obs) between 2430+/-202 and 22.8+/-1.2 h(
      1)), with an order of decreasing activity 2 x (ClO4)4 > 1 x (ClO4)2 > 3 x (ClO4)2
      >> 4 x (ClO4)2. A correlation of the catecholase activities with the variation in
      Cu...Cu distances, as well as other effects resulting from the distinct redox
      potentials, neighboring groups, and the individual coordination spheres are
      discussed. Saturation behavior for the rate dependence on substrate concentration
      was observed in only two cases, that is, for the most active 2 x (ClO4)4 and for
      the least active 4 x (ClO4)2, whereas a catalytic rate that is almost independent
      of substrate concentration (within the range studied) was observed for 1 x
      (ClO4)2 and 3 x (ClO4)2. H2O2 was detected as the product of O2 reduction in the
      catecholase reaction of the three most active systems. The structures of the
      adducts of "L3Cu2" and "L4Cu2" with a substrate analogue (tetrachlorocatecholate,
      TCC) suggest a bidentate substrate coordination to only one of the copper ions
      for those catalysts that feature short ligand side arms and correspondingly
      exhibit larger metal-metal separations; this possibly contributes to the lower
      activity of these systems. TCC binding is supported by several H-bonding
      interactions to water molecules at the adjacent copper or to ligand-side-arm N
      donors; this emphasizes the importance of functional groups in proximity to the
      bimetallic active site.

PMID- 11822457
TI  - Application of the AAA reaction to the synthesis of the furanoside of C-2-epi
      hygromycin A: a total synthesis of C-2-epi-hygromycin A.
AB  - A strategy for stereocontrolled syntheses of furanoside type of natural products
      is developed for a glycosyl aryl ether. This strategy resolves the issue of low
      diastereoselectivity typical of normal glycosidation methods for furanosides. All
      the stereochemistry ultimately derives from a desymmetrization of a 2,5-diacyloxy
      2,5-dihydrofuran using Pd catalyzed asymmetric allylic alkylation which sets both
      the absolute stereochemistry and 1,4-relative stereochemistry. Diastereo
      controlled elaboration of the 3,4-double bond then completes the synthesis. A new
      conjunctive reagent, 1-nitro-1-phenylsulfonyl-ethane, is developed to serve as an
      acyl anion equivalent. The utility of a phenol as a nucleophile in the Pd
      catalyzed glycosylation is demonstrated. From this strategy emerged a short,
      practical synthesis of C-2-epi-hygromycin A.

PMID- 11822458
TI  - Phosphoramidate-mediated conversion of carbonyl ligands into isocyanide ligands:
      a new approach to chiral isocyanide ligands.
AB  - Metal isocyanides have been used and studied by organometallic chemists for many
      years and, as a result, they have a rich and interesting chemistry. The nature of
      metal-free isocyanides and the methods of making isocyanide complexes, however,
      has resulted in the vast majority of studies to date being performed with
      structurally simple isocyanides. We report here a new approach to the synthesis
      of isocyanide ligands that involves the reaction of a metal carbonyl ligand with
      the anion of a phosphoramidate. As phosphoramidates can be synthesised in one
      step from amines, our method means that the structural diversity of readily
      available amines, particularly chiral amines, can now be incorporated into
      isocyanide ligands.

PMID- 11822459
TI  - Ising-type magnetic anisotropy in a cobalt(II) nitronyl nitroxide compound: a key
      to understanding the formation of molecular magnetic nanowires.
AB  - The compound [Co(hfac)2-(NITPhOMe)2] (2) (hfac = hexafluoroacetylacetonate,
      NITPhOMe = 4'-methoxyphenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide)
      crystallizes in the triclinic P1 space group, a= 10.870(5), b = 11.520(5), c =
      19.749(5) A, alpha = 78.05(5), beta = 84.20(5), gamma = 64.51(5) degrees, Z = 2.
      It can be considered a model system for studying the nature of the magnetic
      anisotropy of [Co(hfac)2(NITPhOMe)] (1), which was recently reported to behave as
      a molecular magnetic wire. The magnetic anisotropy of 2 was investigated by EPR
      spectroscopy and SQUID magnetometry both in the polycrystalline powder and in a
      single crystal. The experimental magnetic anisotropy was related to the
      anisotropy of the central ion and to the exchange interaction between the
      cobalt(II) ion and the radicals.

PMID- 11822461
TI  - Supramolecular synthesis through dihydrogen bonds: self-assembly of controlled
      architectures from NaBH4 x poly(2-hydroxyethyl)cyclen building blocks.
AB  - A systematic investigation of molecular structures/supramolecular organization
      relationships in dihydrogen-bonded complexes comprising NaBH4 and poly-2
      hydroxyethyl-cyclen (poly-HEC) building blocks is reported. Like in the prototype
      compound 1, a (NaBH4-poly-HEC)2 dimeric arrangement has been found in the
      analogous structures 3 and 5, but not in compound 2, which lacks dihydrogen
      bonds. The exact connectivity of the dimers is determined by a complex interplay
      of noncovalent interactions such as OH...HB dihydrogen bonds, OH...O conventional
      hydrogen bonds, Na-O and Na-N coordinative bonds, and dispersion interactions.
      The persistent recurrence of this general supramolecular motif permits controlled
      assembly of extended networks with desired architectures, by the use of
      appropriate spacers for linking the dimers, as demonstrated by the solid-state
      structure of 7. Additionally, the intrinsic solid-state reactivity of these
      dihydrogen-bonded networks makes this approach a promising strategy for the
      rational construction of functional extended covalent solids.

PMID- 11822460
TI  - Synthesis, stability, and conformation of the formamidopyrimidine G DNA lesion.
AB  - The formamidopyrimidine (FapydGua) lesion, derived from the nucleobase guanine,
      is a major DNA lesion involved in mutagenesis and carcinogenesis. To date, the
      chemical information available about this main lesion is very limited. Herein, we
      describe a synthesis and a detailed characterization of the acetyl-protected
      monomer of the FapydGua lesion. Stability studies in DMSO and in
      water/acetonitrile show that the N-glycosidic bond, previously thought to be
      highly labile, is much more stable than anticipated. Decomposition of the
      FapydGua lesion proceeds with half-life times of 37.8 h for the beta-anomer and
      65.2 h for the alpha-anomer in water/acetonitrile. The relaxation time for the
      anomerization reaction was determined to tau = 6.5 h at room temperature. Most
      important, it was found that the formamido group, which is critical for the
      lesion recognition process by repair enzymes, is fixed in the cis-conformation in
      apolar solvents such as chloroform. This conformation enables the formation of a
      hydrogen bond between the carbonyl oxygen of the formamide and the NH of the N
      glycosidic bond within the framework of a seven-membered ring system. This has
      consequences for the recognition of the lesion by repair enzymes (hOGG1 and Fpg
      protein). These enzymes were so far believed to recognize the carbonyl group of
      the FapydGua lesion. Our investigations show that this carbonyl group is not
      readily accessible because it is almost buried in the dominating cis
      conformation. In agreement with the recent X-ray structure of hOGG1 in complex
      with 8-oxo-7,8-dihydroguanine-containing DNA, we can conclude that repair enzymes
      can contact both lesions only via the N(7)-H group, which is a hydrogen-bond
      acceptor in guanine.

PMID- 11822462
TI  - A new family of mixed-valence dinuclear rhodium complexes containing the two
      metal centers in different stereochemical environments.
AB  - A series of dinuclear chelate complexes of the general composition [Rh2(kappa2
      L)2(mu-CR2)2(mu-SbiPr3)] (R = Ph, p-Tol; L = CF3CO2-, acac-, acac-f3-) and
      [Rh2Cl(kappa2-L)(mu-CR2)2(mu-SbiPr3)] (R = Ph, p-Tol; L = acac-, acac-f3-) has
      been prepared by replacement of the chloro ligands in the precursors [Rh2Cl2(mu
      CR2)2(mu-SbiPr3)] by anionic chelates. The lability of the SbiPr3 bridge in the
      rhodium dimers is illustrated by the reactions of [Rh2(kappa2-acac)2(mu-CR2)2(mu
      SbiPr3)] (7, 8) with Lewis bases such as CO, CNtBu, and SbEt3 which lead to the
      formation of the substitution products [Rh2(kappa2-acac)2(mu-CR2)2(mu-L')] (13
      16) in excellent yields. Treatment of 7 and 8 with sterically demanding tertiary
      phosphanes PR3 (R3 = iPr3, iPr2Ph, iPrPh2, Ph3) affords the mixed-valence Rh0
      RhII complexes [(kappa2-acac)2Rh(mu-CPh2)2Rh(PR3)] (21-24) and [(kappa2
      acac)2Rh(mu-C(p-Tol)2]2Rh(PiPr3)] (25) for which there is no precedence. The
      terminal PiPr3 ligand of 21 is easily displaced by alkynes, CNtBu, and CO to
      give, by preserving the [(kappa2-acac)2Rh(mu-CPh2)2Rh] molecular core, the
      related dinuclear compounds 26-31 in which the coordination number of the Rh0
      center is 3, 4, or 5. The molecular structures of [Rh2Cl(kappa2-acac)(mu
      CPh2)2(mu-SbiPr3)] (5), [Rh2(kappa2-acac)2(mu-CPh2)2(mu-CO)] (13), [(kappa2
      acac)2Rh(mu-CPh2)2Rh(PiPr3)] (21), and [(kappa2-acac)2Rh(mu-CPh2)2Rh(CNtBu)2]
      (30) have been determined crystallographically.

PMID- 11822463
TI  - The aldol addition reaction: an old transformation at constant rebirth.
AB  - The main recent conceptual advances in asymmetric aldol reactions are presented.
      Methods ranging from stoichiometric chiral auxiliary-mediated to direct,
      catalytic reactions are covered, including the Mukaiyama aldol reactions which
      use stoichiometric base and silylating reagents, but catalytic
      (substoichiometric) amounts of the chiral inductor. The salient features of each
      new development are noted, paying special attention to practical concerns and to
      the potential implementation for large scale production. After examination of
      pros and cons of each strategy, gaps and limitations that deserve further
      investigation are highlighted.

PMID- 11822464
TI  - New mono- and tricyclopalladated dendritic systems with encapsulated catalytic
      sites.
AB  - The preparation of a series of new macrocyclic carbodiazasilane molecules
      functionalized with the monoanionic [2,6-(CH2NMe2)2C6H3](-)[triple bond]N,C,N
      pincer ligand has been accomplished. Palladation of these systems was possible
      through oxidative addition with [Pd(dba)2] affording exclusive formation of the
      meso diastereoisomer. The X-ray crystal structures of these novel ligands and of
      the palladium(II) complex 10 were determined and confirmed the stereochemistry of
      the organopalladium cage. Attachment of the para-OH functionalized
      carbodiazasilane macrocycle 16 to a central core led to the formation of the
      dendritic structure 18 which was palladated to afford the novel multimetallic
      dendritic system with encapsulated catalytic sites 1. This cyclopalladated
      carbosilane dendrimer (1) as well as the mononuclear organopalladium cage 10 can
      be conveniently converted into active Lewis acid catalysts for the aldol
      condensation reaction. The catalytic data showed higher reaction rates for the
      dendritic structure than for the corresponding mononuclear systems.

PMID- 11822465
TI  - Towards the experimental decomposition rate of carbonic acid (H2CO3) in aqueous
      solution.
AB  - Dry carbonic acid has recently been shown to be kinetically stable even at room
      temperature. Addition of water molecules reduces this stability significantly,
      and the decomposition (H2CO3 + nH2O --> (n+1)H2O + CO2) is extremely accelerated
      for n = 1, 2, 3. By including two water molecules, a reaction rate that is a
      factor of 3000 below the experimental one (10 s(-1)) at room temperature was
      found. In order to further remove the gap between experiment and theory, we
      increased the number of water molecules involved to 3 and took into consideration
      different mechanisms for thorough elucidation of the reaction. A mechanism
      whereby the reaction proceedes via a six-membered transition state turns out to
      be the most efficient one over the whole examined temperature range. The
      determined reaction rates approach experimental values in aqueous solution
      reasonably well; most especially, a significant increase in the rates in
      comparison to the decomposition reaction with fewer water molecules is found.
      Further agreement with experiment is found in the kinetic isotope effects (KIE)
      for the deuterated species. For water-free carbonic acid, the KIE (i.e.,
      kH2CO3/kD2CO3) for the decomposition reaction is predicted to be 220 at 300 K,
      whereas it amounts to 2.2-3.0 for the investigated mechanisms including three
      water molecules. This result is therefore reasonably close to the experimental
      value of 2 (at 300 K). These KIEs are in much better accordance with the
      experiment than the KIE for decomposition with fewer water entities.

PMID- 11822466
TI  - Nitroxyl peptides as catalysts of enantioselective oxidations.
AB  - The achiral, nitroxyl-containing alpha-amino acid TOAC (TOAC = 2,2,6,6
      tetramethylpiperidine-1-oxyl-4-amino-4-carboxylic acid), in combination with the
      chiral alpha-amino acid C(alpha)-methyl valine [(alphaMe)Val], was used to
      prepare short peptides (from di- to hexa-) that induced the enantioselective
      oxidation of racemic 1-phenylethanol to acetophenone. The best catalyst was an
      N(alpha)-acylated dipeptide alkylamide with the -TOAC-(alphaMe)Val- sequence
      folded in a stable, intramolecularly hydrogen-bonded beta-turn conformation with
      large, lipophilic (hydrophobic) N- and C-terminal blocking groups. We
      rationalized our findings by proposing models for the diastereomeric
      intermediates between (R)-[and (S)]-1-phenylethanol and the catalyst Fmoc-TOAC-L
      (alphaMe)Val-NHiPr, based on the X-ray diffraction structure of the latter.

PMID- 11822467
TI  - Fluorescence sensing of ionic analytes in water: from transition metal ions to
      vitamin B13.
AB  - The fluorescence chemosensor ATMCA has been realised by appending an
      anthrylmethyl group to an amino nitrogen of TMCA (2,4,6-triamino-1,3,5
      trimethoxycyclohexane), a tripodal ligand selective for divalent first-row
      transition metal ions in water. The ATMCA ligand can act as a versatile sensor
      for ZnII and CuII ions. Its sensing ability can be switched by simply tuning the
      operating conditions. At pH 5, ATMCA detects copper(II) ions in aqueous solutions
      by the complexation-induced quenching of the anthracene emission. Metal ion
      concentrations < 1 microM can be readily detected and very little interference is
      exerted by other metal ions. At pH 7, ATMCA signals the presence of ZnII ions at
      concentrations < 1 microM by a complexation-induced enhancement of the
      fluorescence. Again the sensor is selective for ZnII over several divalent metal
      ions, with the exception of CuII, CoII and HgII. Most interestingly, the
      [ZnII(atmca)]2+ complex can act as a fluorescence sensor for specific organic
      species, notably selected dicarboxylic acids and nucleotides, by the formation of
      ternary ligand/zinc/substrate complexes. The oxalate anion is detected in
      concentrations <0.1 mM; however, no effects on the system's fluorescence is
      observed in the presence of monocarboxylic acids and long-chain dicarboxylic
      acids. Among the nucleotides, those containing an imide or amide function are
      readily detected and an unprecedented high sensitivity for guanine derivatives
      allows the determination of this nucleotide for 0.05-0.5 mM solutions. Moreover,
      [ZnII(atmca)]2+ is a very effective and selective sensor in the case of vitamin
      B13 (orotic acid) in sub-micromolar concentrations. The operative features of the
      systems investigated are also clearly suitable for intracellular analyses. The
      factors at the source of organic substrate recognition, here briefly discussed,
      are of paramount importance for further developments in the applicability of
      these sensing systems.

PMID- 11822468
TI  - Effect of moderate exercise on immune senescence in men.
AB  - The purpose of this study was to examine the relationship between active compared
      to inactive lifestyles and immunocompetence in men. Subjects, all male
      volunteers, regularly exercising moderately were separated into three age groups:
      young (20-39 years), middle-aged (40-59 years) and elderly (more than 60 years).
      Age-matched sedentary male subjects served as controls in each group.
      Immunological assessments were, total leucocyte count, lymphocyte subpopulation
      counts, natural killer cell activity and neutrophilic phagocytosis. Total
      leucocyte and T-cell (CD3+) counts were not significantly different among the
      groups. Among T-cell subsets, there was a slight increase in helper T-cell
      (CD3+CD4+) and a decrease in cytotoxic/suppressor T-cell (CD3+CD8+)
      concentrations in the older sedentary subjects, resulting in an age-associated
      significant increase in the CD4:CD8 ratio among those control groups. However,
      among the exerciser groups, no such increase and decrease in the T-cell
      subpopulations or an age-related increase of the CD4:CD8 ratio were observed.
      Considering the components of innate immunity, the concentration of NK-cells
      (CD16+CD56+) significantly increased in the elderly exercisers, compared to that
      of the age-matched control subjects, or of the young group. The phagocytotic
      activity of neutrophils showed an age-associated decline, but of lesser degree in
      the elderly exercisers than in the elderly controls. Taken together, these
      results suggest that habitual and moderate training in later life is associated
      with a lesser age-related decline in certain aspects of circulating T-cell
      function and innate immunity.

PMID- 11822469
TI  - Skeletal muscle adaptations in elastic resistance-trained young men and women.
AB  - Skeletal muscle adaptations (fiber-type composition, cross-sectional area, myosin
      heavy chain (MHC) content, and capillarity) were assessed in the vastus lateralis
      muscle of young men and women after 8 weeks of training with the Sportcord, an
      elastic resistance device. Ten men [mean (SD) age 20 (1.1) years] and 13 women
      [20 (1.2) years] performed two sets each to failure of single leg squats and leg
      extensions at approximately 50 repetitions x min(-1). Biopsy samples were taken
      from the right vastus lateralis muscle before and after training. Six fiber types
      (I, IC, IIC, IIA, IIAB, and IIB) were classified using myofibrillar ATPase
      histochemistry. Training with the Sportcord caused a small, but significant,
      increase in one-repetition maximum using free weights and a large increase in
      repetitions to failure. In addition, elastic resistance training caused an
      increase in the percentage of fibers classified as type IIAB for both men and
      women, and a decrease in the percentage of type IIB fibers in the men. MHC
      analysis supported these findings (a significant increase in the percentage of
      MHCIIa for the men). The cross-sectional areas ofboth the type I and IIAB + IIB
      fibers increased after training for the men, whereas no area changes were found
      for the women. The capillary:fiber ratio and capillary contacts per fiber type
      increased significantly for the men, and similar trends were noted for the women.
      Capillary density did not change in either the men or the women. These data
      suggest minor changes in fiber type composition (IIB-->IIAB), fiber size, and
      capillarization following short-term training with elastic resistance. Although
      muscular changes did occur using the Sportcord, the extent of these changes was
      less than those reported previously for short-term resistance-training programs
      using free weights.

PMID- 11822470
TI  - Noninvasive assessment of arterial distensibility in adolescents using the second
      derivative of photoplethysmogram waveform.
AB  - To clarify the clinical usefulness of the second derivative of the waveform of
      the fingertip photoplethysmogram (SDPTG), we examined the relationship between
      the pattern of the SDPTG waveform and risk factors related to atherosclerosis in
      1,495 boys and girls aged 9-17 years. The fingertip photoplethysmogram and its
      second derivative wave were automatically recorded from the second digit of the
      right hand with the subjects lying in a supine position. The SDPTG waveform
      consisted of a, b, c and d waves in systole and an e wave in diastole. The
      heights of the a and d waves were measured from the baseline, and the ratio of
      the height of the d wave to that of the a wave (d/a ratio) was calculated. The
      d/a ratio had a negative correlation with the systolic (SBP) and diastolic blood
      pressures (DBP), atherogenic index (AI) and immunoreactive insulin concentrations
      (IRI) after adjustment for age. Multiple linear regression analysis revealed that
      the d/a ratio was associated more with body height than the risk factors for
      atherosclerosis in boys and girls at the growth period. The effect of sex- and
      height-specific cutoff values of the 10th percentile for the d/a ratio was
      therefore tested. The results showed that subjects with d/a ratios lower than the
      10th percentile had significantly higher SBP, DBP, AI and IRI values compared to
      those with higher d/a ratios. These findings suggest that differences in the
      length of the vascular system, which are related to increases in body height, may
      modify the SDPTG waveform pattern during adolescence. When the body height as
      well as age and sex is adequately allowed for, the d/a ratio may be useful for
      the evaluation of arterial distensibility and for identification of individuals
      at an increased risk of developing atherosclerosis.

PMID- 11822471
TI  - Effect of prior metabolic rate on the kinetics of oxygen uptake during moderate
      intensity exercise.
AB  - Pulmonary oxygen uptake (VO2) dynamics during moderate-intensity exercise are
      often assumed to be dynamically linear (i.e. neither the gain nor the time
      constant (tau) of the response varies as a function of work rate). However,
      faster, slower and unchanged VO2 kinetics have been reported during work-to-work
      transitions compared to rest-to-work transitions, all within the moderate
      intensity domain. In an attempt to resolve these discrepancies and to improve the
      confidence of the parameter estimation, we determined the VO2 response dynamics
      using the averaged response to repeated exercise bouts in seven healthy male
      volunteers. Each subject initially performed a ramp-incremental exercise test for
      the estimation of the lactate threshold (thetaL). They then performed an average
      of four repetitions of each of three constant-work-rate (WR) tests: (1) between
      20 W and a work rate of 50% (WR50) between 20 W and 90% thetaL (step 1-->2), (2)
      between WR50 and 90% thetaL (step 2-->3), and (3) between 20 W and 90% thetaL
      (step 1-->3); 6 min was spent at each work rate increment and decrement.
      Parameters of the kinetic response of phase II VO2 were established by non-linear
      least-squares fitting techniques. The kinetics of VO2 were significantly slower
      at the upper reaches of the moderate-intensity domain (step 2-->3) compared to
      steps 1-->2 and 1-->3 [group mean (SD) phase II tau: step 1-->2 25.3 (4.9) s,
      step 2-->3 40.0 (7.4) s and step 1-->3 32.2 (6.9) s]. The off-transient values of
      tau were not significantly different from each other: 36.8 (16.3) s, 38.9 (11.6)
      s and 30.8 (5.7) s for steps 1-->2, 2-->3 and 1-->3, respectively. Surprisingly,
      the on-transient gain (G, deltaVO2/deltaWR) was also found to vary among the
      three steps [G = 10.56 (0.42) ml x min(-1) W(-1) 11.85 (0.64) ml x min(-1) W(-1)
      and 11.23 (0.52) ml x min(-1) W(-1) for steps 1-->2, 2-->3 and 1-->3,
      respectively]; the off-transient G did not vary significantly and was close to
      that for the on-transient step 1-->3 in all cases. Our results do not support a
      dynamically linear system model of VO2 during cycle ergometer exercise even in
      the moderate-intensity domain. The greater oxygen deficit per unit power
      increment in the higher reaches of the moderate-intensity domain necessitates a
      greater transient lactate contribution to the energy transfer, or a greater
      phosphocreatine breakdown, or possibly both.

PMID- 11822472
TI  - Propranolol affects stress-induced leukocytosis and cellular adhesion molecule
      expression.
AB  - In this study, the impact of the beta-adrenergic antagonist propranolol on
      resting and acute psychological- and physical-stress-induced circulating
      leukocyte numbers and the density of cellular adhesion molecules was
      investigated. In a randomized double-blind crossover design, 45 healthy
      volunteers performed a 15-min public speaking task and 21 subjects performed a 16
      min bicycle exercise after 5 days of ingesting a placebo and after 5 days of
      ingesting 100 mg/day propranolol. One week of ingesting propranolol modestly
      elevated the numbers of CD62L+ (P<0.019) but not CD62L- T-lymphocytes. Moreover,
      propranolol preferentially blunted-psychological stress-induced increases in
      naive T-helper (CD4+CD62L+; P<0.049) and naive T-cytotoxic lymphocytes
      (CD8+CD62L+; P<0.003), as well as activated T-cytotoxic lymphocytes (CD8+CD29+;
      P<0.005). However, exercise-induced increases in leukocyte numbers were enhanced
      following propranolol treatment (P<0.04). In contrast to the effect on the
      numbers of adhesion-molecule-bearing cells, there was only a modest effect of
      propranolol on stress-induced alterations of the density of CD62L, CD54 and
      CD11a. In this study, propranolol treatment interfered with the adrenergic
      regulation of circulating leukocyte numbers by blunting psychological stress
      effects but enhancing exercise effects. Propranolol affected the cell activation
      status to a lesser extent, as reflected by the density of adhesion molecules.

PMID- 11822473
TI  - Effect of glutamine supplementation combined with resistance training in young
      adults.
AB  - The purpose of this study was to assess the effect of oral glutamine
      supplementation combined with resistance training in young adults. A group of 31
      subjects, aged 18-24 years, were randomly allocated to groups (double blind) to
      receive either glutamine (0.9 g x kg lean tissue mass(-1) x day(-1); n = 17) or a
      placebo (0.9 g maltodextrin x kg lean tissue mass(-1) x day(-1); n = 14 during 6
      weeks of total body resistance training. Exercises were performed for four to
      five sets of 6-12 repetitions at intensities ranging from 60% to 90% 1 repetition
      maximum (1 RM). Before and after training, measurements were taken of 1 RM squat
      and bench press strength, peak knee extension torque (using an isokinetic
      dynamometer), lean tissue mass (dual energy X-ray absorptiometry) and muscle
      protein degradation (urinary 3-methylhistidine by high performance liquid
      chromatography). Repeated measures ANOVA showed that strength, torque, lean
      tissue mass and 3-methylhistidine increased with training (P < 0.05), with no
      significant difference between groups. Both groups increased their 1 RM squat by
      approximately 30% and 1 RM bench press by approximately 14%. The glutamine group
      showed increases of 6% for knee extension torque, 2% for lean tissue mass and 41%
      for urinary levels of 3-methylhistidine. The placebo group increased knee
      extension torque by 5%, lean tissue mass by 1.7% and 3-methylhistidine by 56%. We
      conclude that glutamine supplementation during resistance training has no
      significant effect on muscle performance, body composition or muscle protein
      degradation in young healthy adults.

PMID- 11822474
TI  - Single and choice reaction time during prolonged exercise in trained subjects:
      influence of carbohydrate availability.
AB  - The aim of the present study was to examine the effects of prolonged exercise at
      the ventilatory threshold and carbohydrate ingestion on single (SRT) and choice
      (CRT) reaction time. Eight well-trained triathletes completed three testing
      sessions within a 3-week period. Maximal oxygen uptake was determined in the
      first test, whereas the second and the third sessions were composed of a 100-min
      run (treadmill 15 min, overground 70 min, treadmill 15 min) performed at the
      velocity associated with the ventilatory threshold. During these submaximal
      tests, the subjects ingested (in random order) 8 ml x kg(-1) body weight of
      either a placebo (Pl) or 5.5% carbohydrate (CHO) solution prior to the first
      submaximal run and 2 ml x kg(-1) body weight every 15 min after that. The
      cognitive tasks were performed before and after exercise for CRT, and before,
      during each submaximal run and after exercise for SRT. Furthermore, at the end of
      each submaximal test subjects were asked to report their rating of perceived
      exertion (RPE). Results showed a significant positive effect of CHO ingestion on
      RPE and CRT performance at the end of exercise, while no effect of exercise
      duration was found in the Pl condition. After a 100-min run, during the CHO
      condition, CRT mean (SD) group values decreased from 688.5 (51) ms to 654 (63)
      ms, while during the Pl condition, RPE mean group values increased from 11 (2) to
      16 (1.02) and CRT mean values remained stable [688 (104) ms vs 676 (73.4) ms, P >
      0.05]. No similar effect was observed for SRT. These results suggest that CHO
      electrolyte ingestion during a 100-min run results in an improvement in the
      complex cognitive performance measured at the end of that run.

PMID- 11822476
TI  - Oxygen uptake during whole-body vibration exercise: comparison with squatting as
      a slow voluntary movement.
AB  - In this study we investigated metabolic power during whole-body vibration
      exercise (VbX) compared to mild resistance exercise. Specific oxygen consumption
      (VO2) and subjectively perceived exertion (rating of perceived exertion, RPE;
      Borg scale) were assessed in 12 young healthy subjects (8 female and 4 male). The
      outcome parameters were assessed during the last minute of a 3-min exercise bout,
      which consisted of either (1) simple standing, (2) squatting in cycles of 6 s to
      90 degrees knee flexion, and (3) squatting as before with an additional load of
      40% of the subject's body weight (35% in females). Exercise types 1-3 were
      performed with (VbX+) and without (VbX-) platform vibration at a frequency of 26
      Hz and an amplitude of 6 mm. Compared to the VbX- condition, the specific VO2 was
      increased with vibration by 4.5 ml x min(-1) x kg(-1). Likewise, squatting and
      the additional load were factors that further increased VO2. Corresponding
      changes were observed in RPE. There was a correlation between VbX- and VbX+
      values for exercise types 1-3 (r = 0.90). The correlation coefficient between
      squat/no-squat values (r = 0.70 without and r = 0.71 with the additional load)
      was significantly lower than that for VbX-/VbX+. Variation in specific VO2 was
      significantly higher in the squatting paradigm than with vibration. It is
      concluded that the increased metabolic power observed in association with VbX is
      due to muscular activity. It is likely that this muscular activity is easier to
      control between individuals than is simple squatting.

PMID- 11822475
TI  - Adaptation of the left heart, cerebral and femoral arteries, and jugular and
      femoral veins during short- and long-term head-down tilt and spaceflights.
AB  - The objective of this investigation was to identify the major cardiovascular
      changes induced by exposure to real or simulated Og (spaceflights: 6, 14, 21 and
      25 days, and 6 months; head down tilt, HDT: 10 h, 4, 5, 7, 30 and 42 days), with
      a minimum of counter-measures. The following cardiovascular data were measured by
      echocardiography and Doppler ultrasonography: left ventricle end-diastolic volume
      (LVDV), stroke volume (SV), cardiac output (CO), ejection fraction (EF), middle
      cerebral artery flow velocity (Qca), femoral artery flow velocity (Qfa), cerebral
      vascular resistance (Rca), femoral vascular resistance (Rfa), jugular vein cross
      sectional area (Ajv), femoral vein cross-sectional area (Afv), heart rate (HR),
      and mean blood pressure (MBP). LVDV remained decreased compared to pre-HDT or pre
      flight levels after 1 week of spaceflight or HDT (-8 to -13%, P<0.05), EF did not
      change. HR tended to increase (5-10%) during spaceflight and HDT, whereas MBP
      tended to decrease during flight, but did not change in HDT. These findings are
      consistent with the existence of a moderate and stable hypovolemia. Qca and Rca
      fluctuated between +10 and -10% from pre-HDT or pre-flight values, and always
      showed opposing variations. There was no significant decrease in cerebral
      perfusion. Lower-limb resistance (Rfa) remained decreased (-5% to -18%, P<0.05)
      throughout the flights or HDT after week 1. Ajv remained significantly enlarged
      (+40% P < 0.05) after 1 week in spaceflight or in HDT. Afv was enlarged in
      spaceflight after week 1 (+15% to +35%, P<0.05), whereas it decreased after 4-5
      days of HDT (-20% to -35%, P<0.05). The cardiovascular system reached a new and
      stable equilibrium during flight and HDT within less than 1 week. With the
      exception of the femoral vein, there was no significant difference in either the
      amplitude or the time course of the cardiovascular changes in both situations
      after 1 week.

PMID- 11822477
TI  - Oxygen uptake-heart rate relationship in elite wheelchair racers.
AB  - The American College of Sports Medicine (ACSM) recommends that, as a general rule
      for health purposes, individuals should exercise at 40%-85% of their maximal
      oxygen uptakes. Moreover, it has been suggested that 55%-90% of the maximal heart
      rate may be used as an alternative estimate of these percentage maximal oxygen
      uptake values. The present study examined the relationship between percentage
      peak heart rate (% HRpeak) and percentage peak oxygen uptake (% VO2peak) during
      steady-state incremental intensity wheelchair propulsion of 16 elite, male
      wheelchair racers (WR). Oxygen uptake was determined during each submaximal
      exercise stage and heart rate (HR) was continuously monitored. The VO2peak was
      subsequently determined using a separate protocol. Linear regression equations of
      % HRpeak versus % VO2peak for each participant included % HRpeak values
      corresponding to 40%, 60%, 80% and 85% VO2peak. The linear regression equation,
      derived as the group mean of the slope and intercept terms determined for each
      individual, was: % peak HR = 0.681 x % peak VO2 + 33.2. The group mean of the
      individual correlation coefficients for the VO2-HR relationship was 0.99. The
      values of % HRpeak for each of the % VO2peak values below 85% were significantly
      greater (P<0.01) than those suggested by the ACSM. This suggests that the ACSM
      guidelines below 85% VO2peak, based on % HRpeak, may underestimate the relative
      exercise intensity (i.e. % VO2peak) in the WR population. However, in elite level
      WR, % HRpeak can be recommended as an alternative estimate of % VO2peak at
      wheelchair propulsion intensities of 85% VO2peak or more.

PMID- 11822478
TI  - Preliminary results on mood state, salivary testosterone:cortisol ratio and team
      performance in a professional soccer team.
AB  - Mood, as measured by the profile of mood states questionnaire (POMS), salivary
      cortisol (F) and testosterone (T) levels, and performance were examined in 17
      male soccer players 4 times during a season. Soccer players provided three saliva
      samples when getting up (resting values, 8 a.m.), before breakfast (11.30 a.m.),
      and between 4.00 p.m. and 6.00 p.m. The initial measures were performed 1 day
      following the start of season training (T1). They were then performed before and
      after a high-intensity training programme (T2 and T3, respectively) and 16 weeks
      after T3 (T4). Iceberg profiles of POMS were observed during T1, T2 and T3, which
      coincided with successful performance. Subsequent decreased performance between
      T3 and T4 coincided with a decrease in vigor and an increase in tension and
      depression. Indeed, when the normal nycthemeral rhythm for F was observed (i.e. a
      decrease from morning until evening at all times; T1-T4), there was seemingly a
      non-statistical elevation of F on the morning of T3, which only became
      statistically significant at 11.30 a.m. on T3. In spite of a post-high-intensity
      training programme (T3) increase in catabolism, the soccer players presented
      iceberg profiles together with a high percentage of winning. Our results could
      suggest that in team soccer, a decreased T:F ratio does not automatically lead to
      a decrease in team performance or a state of team overtraining. It appears that
      combined psychological and physiological changes during high-intensity training
      are primarily of interest when monitoring training stress in relation to
      performance.

PMID- 11822479
TI  - Relationship among biomechanical, biochemical, and cellular changes associated
      with osteoarthritis.
AB  - Articular cartilage that lines the surface of long bones is a multilayered
      material. The superficial layer consists of collagen fibrils and chondrocytes
      that run parallel to the joint surface. In the deeper layers, the collagen
      fibrils are more randomly arranged and support vertical units termed chondrons
      containing rows of chondrocytes. In the deepest layers, the collagen fibrils run
      almost vertically and ultimately insert into the underlying subchondral bone.
      Osteoarthritis (OA) is a disease that affects articular cartilage and is
      characterized by enzymatic and mechanical breakdown of the extracellular matrix,
      leading to cartilage degeneration, exposure of subchondral bone, pain, and
      limited joint motion. Changes in mechanical properties of articular cartilage
      associated with OA include decreases in modulus and ultimate tensile strength.
      These changes parallel the changes observed after enzymatic degradation of either
      collagen or proteoglycans in cartilage. Results of recent viscoelastic studies on
      articular cartilage suggest that the elastic modulus of collagen and fibril
      lengths decrease in OA and are associated with a loss of the superficial zone and
      a decreased ability of articular cartilage to store elastic energy during
      locomotion. It is suggested that osteoarthritic changes to cartilage involve
      enzymatic degradation of matrix components and fibril fragmentation that is
      promoted by subsequent mechanical loading.

PMID- 11822480
TI  - Hand-transmitted vibration and biodynamic response of the human hand-arm: a
      critical review.
AB  - Hand-arm vibration syndrome (HAVS) has been associated with prolonged exposure to
      vibration transmitted to the human hand-arm system from hand-held power tools,
      vibrating machines, or hand-held vibrating workpieces. The biodynamic response of
      the human hand and arm to hand transmitted vibration (HTV) forms an essential
      basis for effective evaluations of exposures, vibration-attenuation mechanisms,
      and potential injury mechanisms. The biodynamic response to HTV and its
      relationship to HAVS are critically reviewed and discussed to highlight the
      advances and the need for further research. In view of its strong dependence on
      the nature of HTV and the lack of general agreement on the characteristics of
      HTV, the reported studies are first reviewed to enhance an understanding of HTV
      and related issues. The characteristics of HTV and relevant unresolved issues are
      discussed on the basis of measured data, proposed standards, and measurement
      methods, while the need for further developments in measurement systems is
      emphasized. The studies on biodynamic response and their findings are grouped
      into four categories based on the methodology used and the objective. These
      include studies on (1) through-the-hand-arm response, expressed in terms of
      vibration transmissibility; (2) to-the-hand response, expressed in terms of the
      force-motion relationship of the hand-arm system; (3) to-the-hand biodynamic
      response function, expressed in terms of vibration energy absorption; and (4)
      computer modeling of the biodynamic response characteristics.

PMID- 11822481
TI  - British growth charts for height and weight with recommendations concerning their
      use in auxological assessment.
AB  - PRIMARY OBJECTIVE: To review the appropriateness of current British growth charts
      for height and weight. METHODS AND PROCEDURES: A review of their structure and
      function in the context of the problems posed by (1) secular trends for
      increasing size, (2) the external validity of source samples, (3) differences in
      the design and application of cross-sectional and longitudinal charts, and (4)
      the clinical significance of differences between current charts. MAIN OUTCOMES
      AND RESULTS: Charts pre-dating the Freeman et al. 1995 and the Buckler-Tanner
      1995 charts should be considered obsolete for the purposes of growth assessment
      on a sample or individual basis. Either the Freeman or the Buckler-Tanner chart
      is suitable for screening, surveillance or monitoring prior to adolescence but
      the Freeman chart is recommended for screening and surveillance of samples of
      children throughout childhood and adolescence. When comprehensive growth and
      development data are available it is advantageous to use the Buckler-Tanner chart
      during adolescence for the diagnosis and monitoring of individual children.

PMID- 11822482
TI  - Sexual maturation of Greek boys.
AB  - BACKGROUND: Sexual maturation is dependent on genetic and environmental factors,
      therefore each ethnic group has to have its own normative data. AIM: This study
      describes the sexual maturation of Greek boys. SUBJECTS AND METHODS: We examined
      cross-sectionally 1266 healthy boys, aged 8-16 years. Pubertal staging in each
      boy was assessed according to Tanner's classification. Our data were also
      compared with those of a study performed in 1968. RESULTS: The first pubertal
      sign was genital enlargement (G2) that occurred at a mean age of 11.0 (+/- 1.3)
      years followed by pubic hair development (PH2) at 11.5 (+/- 1.5) years of age.
      There was no clear change in pubertal maturation from the 1968 study.
      CONCLUSIONS: The age at which genital development occurs in Greek boys is no
      different from that of other Caucasian populations. However, pubic hair in Greek
      boys develops significantly earlier.

PMID- 11822483
TI  - Gender differences in neonatal subcutaneous fat store in late gestation in
      relation to maternal weight gain.
AB  - OBJECTIVE: To study gender differences in fat store in human newborns and their
      relation to duration of gestation and maternal weight gain. METHODS: The ratios
      subscapular skinfold thickness/body weight (SST/BW) and tricipital skinfold
      thickness/body weight (TST/BW) were calculated in a sample of 13609 premature and
      term neonates from the maternity hospital of Clamart, Hauts-de-Seine, France.
      RESULTS: Whereas BW, SST and TST increased with gestational age, SST/BW and
      TST/BW ratios decreased regularly, in males as in females. This result reflects a
      progressive reduction of subcutaneous fat store per body weight unit as the
      duration of gestation increases. Males had smaller values of SST/BW and TST/BW
      ratios than females whatever the gestational age. Increasing maternal weight gain
      during the third gestational trimester did not improve the subcutaneous fatness
      per body weight unit of the newborn. Earlier amount of maternal weight gain had
      an effect on the TST/BW index exclusively in females. CONCLUSIONS: In newborns, a
      gender difference was observed in the ratio of subcutaneous fat per unit of body
      weight; this ratio is lower in males than in females. This result argues for a
      gender difference in mobilization of fat store to ensure normal growth in the
      last weeks of pregnancy: males lose more fat but gain more weight than females in
      this period. Late maternal weight gain does not affect the proportion of
      subcutaneous fatness by body weight unit in both genders.

PMID- 11822484
TI  - The inverse relationship between bone status and blood pressure among Polish men.
AB  - PRIMARY OBJECTIVE: An evaluation of relationships between bone density and blood
      pressure in healthy men. RESEARCH DESIGN: A cross-sectional population-based
      survey. METHODS AND PROCEDURES: An ethnically homogeneous sample of 208 men, aged
      35-63, healthy and occupationally active inhabitants of the city of Wroclaw,
      Lower Silesia, Poland were studied. Trabecular, cortical and total bone mineral
      content (BMC) at the ultra-distal radius of the non-dominant hand were assessed
      by peripheral Quantitative Computed Tomography (pQCT: Stratec 960 apparatus).
      Body mass index (BMI) was used as a measure of general obesity. Systolic and
      diastolic blood pressure (BP) were measured using an MPC-350 sphygmomanometer.
      Multiple linear regression was used to evaluate the relationships between BP and
      BMC. A two-way analysis of covariance was carried out to test for the
      significance of inter-group differences in BMC with regard to age and BP with BMI
      as a contiuous covariable. Multiple logistic regression was used to verify
      whether some select factors (age, BMI, systolic and diastolic BP) could
      significantly predict male bone status. RESULTS: Systolic BP was not related to
      bone status at the ultra-distal radius. There were no differences in any BMC
      between systolic hyper- and normotensive subjects. Additionally, systolic
      hypertension did not affect the probability of an occurrence of male osteopenia
      (independently of age and BMI). In contrast, there were significant negative
      relationships between diastolic BP, and trabecular and total (but not cortical)
      BMC (even when controlled for age and BMI). Moreover, diastolic hypertensive men
      had reduced BMC at the ultra-distal radius when compared with normotensive
      subjects. It is noteworthy that Polish men of diastolic BP exceeding 90 mmHg had
      an approximately 1.50-fold increased relative risk of being osteopenic when
      compared with normotensive subjects (even when controlled for age, BMI and
      systolic BP). CONCLUSIONS: In the light of the inverse relationship between BMC
      and diastolic BP, Polish men with elevated diastolic BP seem to be more prone to
      the excessive age-related bone loss.

PMID- 11822485
TI  - Regional patterns of birthweights in Papua New Guinea in relation to diet,
      environment and socio-economic factors.
AB  - Regional differences in mean birthweight in rural Papua New Guinea (PNG) and the
      importance of differences in family diet and maternal education and socio
      economic status on such patterns were explored using birthweight data collected
      by the 1982/83 PNG National Nutrition Survey. A total of 6137 birthweight
      measurements from 85 PNG districts were available, representing 22% of all
      children included in the survey. The nature of possible selection biases are
      assessed and their implications discussed. Hierarchical Bayesian spatial models
      based on conditional autoregressive (CAR) priors were used to model spatial
      patterns in birthweights and their relation to different sets of covariates.
      Birthweights were found to exhibit striking geographical differences. Children
      from the central PNG highlands and from affluent lowland areas had the highest
      birthweights, while they were lowest in the (largely lowland) Sepik, Western,
      Madang and Milne Bay Provinces and in remote highland fringe areas. Maternal
      education, socio-economic status and diet were all important predictors, but only
      differences in family diet were correlated with the observed spatial patterns.
      The results of the present study highlight the importance of nutrition and socio
      economic status in explaining differences in birthweights in PNG. Besides
      improving maternal health, interventions for improving birthweights in PNG should
      therefore aim at strengthening the economic base of rural populations and promote
      the cultivation and consumption of high quality foods.

PMID- 11822486
TI  - Short-term growth in children with growth disorders.
AB  - OBJECTIVE: We have previously demonstrated that normal prepubertal growth over 1
      year is composed of growth spurts lasting an average of 8 weeks, separated by
      periods of very slow growth or stasis. We have now analysed short-term growth
      patterns in eight children with different growth disorders: Turner syndrome (n =
      2), intrauterine growth retardation (IUGR, n = 1) and growth hormone (GH)
      deficiency (GHD, n = 5). METHODOLGY: Height was measured daily in the morning by
      parents over 4-12 months. Regression and time series analysis were used to
      characterize short-term growth. In two boys (GHD and IUGR) their normal twin
      brother was measured in parallel. RESULTS: All height velocity curves, based on
      regression analysis, showed a biphasic pattern, characterized by growth spurts of
      varying amplitudes and periods of very slow growth or growth stasis. When
      compared to growth curves in normal children, the principal qualitative
      differences in GHD and Turner syndrome were increased stasis time and reduced
      growth spurt amplitude. In IUGR reduced amplitude and length of growth spurts
      were seen, but the time spent in stasis was similar to normal children. Two naive
      patients with GHD increased the amplitude of their growth spurts by a mean 0.013
      cm day(-1) on GH treatment, with the mean length of their growth spurts
      increasing by 10 days. Their time spent in stasis decreased from 19% to 6% on GH.
      In two subjects with GHD the growth pattern during maintenance GH treatment was
      similar to that seen in normal children. Using time series analysis significant
      periodicities in height measurements were seen in the majority of children with
      growth disorders, which disappeared in patients with GHD in the catch-up phase
      after commencing GH therapy. CONCLUSIONS: (1) The growth spurts and stases seen
      in normal children are also observed in those with growth disorders, (2)
      different growth disorders have variable effects on the spurt stasis model of
      childhood growth, (3) catch-up growth on GH in children with GHD was achieved by
      increasing the amplitude of the growth spurts and reducing the time spent in
      stasis.

PMID- 11822487
TI  - Writing style.

PMID- 11822488
TI  - Interdisciplinary practice--a matter of teamwork: an integrated literature
      review.
AB  - The aim of this literature review is to explore the development of
      interdisciplinary practice. The terms interdisciplinary, multidisciplinary, and
      inter-professional are problematic. Definitions must be viewed carefully, as
      interpretations tend to reflect historical, socialization patterns that are now
      out of kilter with contemporary understandings. Changing inter-professional
      interactions, teams and teamwork are examined; findings indicate that
      explanations of interdisciplinary teamwork should be all-inclusive of the
      particular cultural conditions and contextual determinants that affect team
      practice. Findings need to be viewed with caution because what is applicable in
      one country may not be automatically transferable to another, where particular
      socio-political contexts shape interdisciplinary practice.

PMID- 11822489
TI  - Routine intra-operative assessment of pain and/or depth of anaesthesia by nurse
      anaesthetists in clinical practice.
AB  - Patient safety and comfort during general anaesthesia and surgery are to a
      considerable extent dependent on the capability of anaesthesia personnel to
      interpret directly monitored as well as indirect clinical signs of pain and/or
      depth of anaesthesia. The aim of the present study was to evaluate how nurse
      anaesthetists in their clinical routine work assess and interpret intra-operative
      responses evoked by pain stimuli and/or insufficient depth of anaesthesia. A
      questionnaire was designed to assess the perceived relevance and validity of
      cardiovascular, respiratory, mucocutaneous, eye-associated, and muscular
      responses for routine assessment of intra-operative pain and/or insufficient
      depth of anaesthesia in patients undergoing surgery under general anaesthesia.
      Data were obtained from 223 nurse anaesthetists working at nine different
      university anaesthesia departments in Sweden. A number of significant indicators
      for pain and depth of anaesthesia could be identified for spontaneously breathing
      as well as for mechanically ventilated patients. No variable was considered
      entirely specific for either intra-operative pain or depth of anaesthesia.
      Changes in breathing rate/volume, central haemodynamics (BP, HR), lacrimation,
      and presence of moist and sticky skin were given higher score values as
      indicators of pain than as indicators of depth of anaesthesia. Occurrence of
      grimaces, attempted movements, and presence of non-centred pupils were variables
      considered more indicative of insufficient depth of anaesthesia than intra
      operative pain. In conclusion, it is obvious from the present data that indirect
      physiological signs of intra-operative pain and depth of anaesthesia are still
      considered of importance by Swedish anaesthesia nurses in the anaesthetic
      management of surgical patients.

PMID- 11822490
TI  - Nurses' competence in advising and supporting clients to cease smoking: a survey
      among Finnish nurses.
AB  - The article describes the results of a survey of Finnish nurses (n = 882). The
      purpose of the study was to describe how nurses' education, working experience
      and their own smoking habits relate to their self-reported competence in advising
      and supporting clients to cease smoking. Nurses evaluated their skills fairly
      highly, but did not believe that advice alone was helpful to clients who wished
      to cease smoking. Nurses had minimal knowledge of smoking substitutes. Lower
      general education, a fairly short time from graduation and a history of smoking
      were positively related to nurses' competence to guide clients. Nurses who smoked
      daily were found to have better skills in giving advice and support than their
      non-smoking colleagues. The results have implications for the design of smoking
      cessation programmes. More education and guidance is required for nurses, so that
      they can develop their understanding and a positive view as to the effectiveness
      of smoking cessation programmes.

PMID- 11822491
TI  - Nurse-doctor interactions during critical care ward rounds.
AB  - This paper describes the participation of critical care nurses in ward rounds,
      and explores the power relations associated with the ways in which nurses
      interact with doctors during this oral forum of communication. The study
      comprised a critical ethnographic study of six registered nurses working in a
      critical care unit. Data collection methods involved professional journalling,
      participant observation, and individual and focus group interviews with the six
      participating nurses. Findings demonstrated that doctors used nurses to
      supplement information and provide extra detail about patient assessment during
      ward rounds. Nurses experienced enormous barriers to participating in decision
      making activities during ward round discussions. By challenging the different
      points of view that doctors and nurses might hold about the ward round process,
      the opportunity exists for enhanced participation by nurses.

PMID- 11822492
TI  - Patterns of Japanese clinical nursing: a historical analysis.
AB  - One of the distinct patterns in the history of modern Japanese nursing during the
      past 120 years has been the uncritical acceptance of western nursing with little
      regard given to Japanese culture. The purpose of this article is to give a
      critical analysis of Japanese nursing in order to demonstrate how deeply culture
      influences nursing. I suggest that good communication among doctors and nurses,
      and among health professionals and patients is the key to the advancement of
      Japanese nursing.

PMID- 11822493
TI  - Healthcare personnel's attitudes towards patients with urinary incontinence.
AB  - The aim of the study was to understand the variability of Norwegian staff's
      attitudes towards patients with urinary incontinence across years and place of
      work, age and education levels. The Incontinence Stress Questionnaire-Staff
      Reaction (Norwegian version) (ISQ-SR-N) was used to measure staff's reactions and
      feelings towards patients with urinary incontinence. A cross-sectional survey
      design was used to gather self-reported data. The research sites were five
      nursing homes, three home care districts and medical and surgical wards at a
      university hospital. Of the 745 staff invited, 535 (72%) returned the
      questionnaire. Staff members working in long-term care units were older than
      staff members working in acute care units. Most of the registered nurses worked
      in acute care, whilst most of the nursing assistants worked in long-term care.
      Stepwise regression analysis identified education, working in a medical/surgical
      units, and the interaction of education and working in a medical unit to be most
      predictive of attitudes. Nursing assistants had more positive attitudes than
      registered nurses. Working in medical/surgical units predicted the most negative
      attitudes. Only 15.2% of the variability of attitudes can be explained by the
      predictive variables.

PMID- 11822494
TI  - Screening swallowing function of patients with acute stroke. Part one:
      Identification, implementation and initial evaluation of a screening tool for use
      by nurses.
AB  - Stroke is a major cause of acute and chronic disability in the developed world,
      producing a wide range of impairments, including dysphagia, which impact upon
      eating. Dysphagia affects between one and two thirds of patients with acute
      stroke, with the potential for life-threatening airway obstruction, aspiration
      pneumonia and malnutrition. Whilst associated with increased impairment,
      dysphagia may present in isolation or accompanied by minimal disability;
      universal screening of swallowing function is recommended. This study describes
      the process undertaken to review the evidence for dysphagia screening methods in
      patients with acute stroke. It also identifies, implements and establishes
      sensitivity and specificity of a screening tool (the Standardized Swallowing
      Assessment, SSA) for use by nurses. Not all ward staff had completed training to
      use the SSA by conclusion of the patient audit. Nonetheless 123 out of 165
      assessable patients (74.5%) had their swallow function screened, 64 by SSA (52%).
      Based on 68 completed screening episodes by independently competent nurses, a
      comparison with summative clinical judgement of swallow function revealed a
      sensitivity of 0.97 and specificity of 0.9 for detection of dysphagia, with
      positive and negative predictive values of 0.92 and 0.96. This was significantly
      better than gag reflex performance, supporting the use of the SSA by competent
      ward nurses.

PMID- 11822495
TI  - Screening swallowing function of patients with acute stroke. Part two: Detailed
      evaluation of the tool used by nurses.
AB  - Stroke is a common problem and a major consumer of health and social care budgets
      in the UK. Dysphagia is a frequent accompaniment and its management has the
      potential to exert significant influence within the rehabilitation process. This
      study explores in detail the performance of a screening tool (based on the
      Standardized Swallowing Assessment) used by nurses. Based on 68 complete
      screening episodes by independently competent nurses, with the effects of chance
      removed, the tool demonstrated good agreement with summative clinical judgement
      of swallow function (kappa = 0.88). The accuracy of results supported the full
      training and education programme for nurses. Not all components of the tool were
      required; analyses suggested elimination of three variables but further
      exploration is warranted. As a component of evidence-based guidelines for
      nutritional support in acute stroke, the screening initiative contributed to
      improved patient outcomes.

PMID- 11822496
TI  - Complications associated with enteral nutrition by nasogastric tube in an
      internal medicine unit.
AB  - Enteral nutrition through a nasogastric tube is a technique often used with
      hospitalized patients when they present problems with oral nutrition. Patients
      receiving enteral nutrition show several kinds of complications such as
      diarrhoea, vomiting, constipation, lung aspiration, tube dislodgement, tube
      clogging, hyperglycaemia and electrolytic alterations. We present a prospective
      and observational study carried out in an Internal Medicine Unit with 64 patients
      who were fed by a nasogastric tube. From the results it can be seen that older
      people represented a majority (the average age was 76.2 years), and difficulty in
      swallowing was the main reason for beginning enteral nutrition. The complications
      which appeared were: tube dislodgement (48.5%); electrolytic alterations (45.5%);
      hyperglycaemia (34.5%); diarrhoea (32.8%); constipation (29.7%); vomiting
      (20.4%); tube clogging (12.5%); and lung aspiration (3.1%). We discuss the
      possible relationship between the different factors associated with the enteral
      nutrition procedure and the occurrence of these complications. Finally, some
      nursing interventions are suggested, such as: checking the gastric residue
      periodically; attempting to place the tube in the duodenum in unconscious
      patients; and the use of protective mittens in disturbed patients.

PMID- 11822497
TI  - Individually adjusted meals for older people with protein-energy malnutrition: a
      single-case study.
AB  - The objective of this study was to investigate the effect of a 3-month
      intervention programme consisting of meals based on individual nutritional
      requirements in residents assessed as protein-energy malnourished on admission to
      a municipal care Institution. Using a single-case design, 11 malnourished
      residents were given individual care aimed at fulfilling their personal
      requirements for energy intake during a period of 12 weeks. The residents were
      selected from a sample of 261 newly admitted older adults of whom 87 were
      assessed to be malnourished on admission. Nutritional status, including
      anthropometric and biochemical variables and functional capacities were assessed
      before, during, and after the intervention. Energy intake was recorded every day.
      Body weight, and serum concentration of albumin and transthyretin were measured
      every other week. During a 3-month period, the mean value of energy intake
      reached the calculated energy requirement in 10 residents. Eight residents
      increased in weight, triceps skin-fold thickness, and transthyretin
      concentration. Nine residents increased in arm muscle circumference, and 10
      showed increased serum albumin concentration and functional capacity. We conclude
      that nursing care based on individual nutritional requirements, resources, and
      desires improves nutritional status and functional capacity in a group of
      malnourished residents.

PMID- 11822498
TI  - Stressors and coping methods among chronic haemodialysis patients in Hong Kong.
AB  - The purpose of the study was to determine the stressors and coping methods of
      chronic haemodialysis patients in Hong Kong. Relationships among treatment
      related stressors, coping methods and length of time on haemodialysis were
      explored. Fifty subjects completed the Haemodialysis Stressor Scale (HSS) and
      Jalowiec Coping Scale (JCS). Results revealed that limitation of fluid was the
      most frequently identified stressor, followed by limitation of food, itching,
      fatigue and cost. The most common coping methods are 'accepted the situation
      because very little could be done', followed by 'told oneself not to worry
      because everything would work out fine' and 'told oneself that the problem was
      really not that important.' It was found that the traditional philosophies of the
      Chinese--Confucianism, Buddhism, and Taoism--share an approach to the
      understanding and management of life stressors as different from that adopted by
      Western philosophies. The findings of this study can further facilitate nurse
      practitioners in providing support, information, and alternative solutions when
      assisting patients in coping with long-term haemodialysis.

PMID- 11822499
TI  - Women's lived experience of breast biopsy: a phenomenological study.
AB  - This study aimed to explore Irish women's lived experience of breast biopsy with
      a view to gaining a deeper understanding of their individual experiences and the
      meanings that it holds for them. A phenomenological approach from a Heideggerian
      hermeneutical perspective was used. Study participants were eight women aged 22
      54 years who had experienced a recent breast biopsy with benign diagnosis. Data
      were collected using in-depth interviewing. The work of Benner (1994), together
      with guidelines from Morse & Field (1996) and Burnard (1991) were used to guide
      the process of data analysis. Themes which emerged from the data were: 'Finding
      the lump', 'Waiting, not knowing', 'knowing', 'Getting back to normal' and
      'Reflections'. Women's feelings of initial distress followed by relief permeate
      these themes.

PMID- 11822500
TI  - A phenomenological study of pain following fractured shaft of femur.
AB  - There is very little work that discusses the pain experience following fractured
      shaft of femur. Therefore, an exploratory phenomenological study of the
      individual experience of pain following a traumatic fracture of the shaft of
      femur was conducted. Two key themes emerged: the injury experience and the pain
      experience, both linked to the need to maintain physical integrity. The findings
      underline the highly complex nature of the pain experience and illustrate the
      range of experiences that individuals with traumatic fractures are exposed to.
      The findings have implications for the nursing and medical management of patients
      following long bone fracture.

PMID- 11822502
TI  - Gender differences and fears in patients awaiting coronary artery bypass
      grafting.
AB  - The study aimed at ascertaining the gender differences and fears among patients
      awaiting coronary artery bypass grafting. Data were collected using a mailed
      questionnaire from patients (n=207) scheduled for coronary artery bypass grafting
      at one hospital. Intensity of fear was measured on a 10-point scale including 12
      objects of fear. The results showed that demographic data, lifestyle and
      functional capacity differed between the sexes. Patients' fears differed with
      respect to their objects and intensity, with women reporting more intense fears.
      Men also had fears, but the objects of fear differed from those in women. Apart
      from gender, the intensity of fear was associated with physical exercise,
      emotional problems and depression. Nursing interventions could be developed to
      meet the different needs for information and support, especially among women but
      also among men, to relieve their fears during the wait for coronary artery bypass
      grafting.

PMID- 11822501
TI  - 'Brothers in arms': how men with cancer experience a sense of comradeship through
      group intervention which combines physical activity with information relay.
AB  - The study investigated how a group intervention programme (13 sessions over 16
      weeks), designed for men with cancer (n = 17), affected their sense of well-being
      and had a positive impact on their ability to cope with the physical,
      psychological and social consequences of living with cancer. The close-knit
      relationships fostered between participants stimulated a sense of solidarity and
      commitment amongst them. New thinking in relation to gender, group dynamics and
      social processes is presented, as are the implications for clinical nursing
      practice in cancer care. The experience from male orientated group intervention
      programmes shows that men with cancer have undiscovered strengths, whilst some
      wish to die 'with their boots on'.

PMID- 11822503
TI  - Is good 'quality of life' possible at the end of life? An explorative study of
      the experiences of a group of cancer patients in two different care cultures.
AB  - The purpose of this paper was to explore how a group of gravely ill patients,
      cared for in different care cultures, assessed their quality of life during their
      last month of life. The study material comprised quality of life assessments from
      47 cancer patients, completed during their last month of life. Two quality of
      life questionnaires, the EORTC QLQ-C30 and a psychosocial well-being
      questionnaire, were used. The data were treated in accordance with instructions
      for the respective questionnaires, and the results are presented primarily as
      means, mostly at the group level. Assessments from patients in two different care
      cultures, care-orientated and cure-orientated, were compared. The results show
      that despite having an assessed lower quality of life in many dimensions than
      people in general, several patients experienced happiness and satisfaction during
      their last month of life. 'Cognitive functioning' and 'emotional functioning'
      were the dimensions that differed least from those of the general population, and
      'physical functioning', 'role functioning' and 'global health status/quality of
      life' differed the most. 'Fatigue' showed the highest mean for the symptom
      scales/items. There was a tendency for those cared for in the cure-orientated
      care culture to report more symptoms than those in the care-orientated care
      culture. An exception to this was 'pain', which was reported more often by those
      in the care-orientated care culture. The implications of the results are
      discussed from different angles. The significance of knowledge concerning how
      patients experience their quality of life is also discussed with respect to the
      care and the planning of care for dying patients.

PMID- 11822504
TI  - Life situation of patients with an implantable cardioverter defibrillator: a
      descriptive longitudinal study.
AB  - The aim of this study was to describe changes in the life situation of patients
      with an implantable cardioverter defibrillator over a period of 1 year. A sample
      of 56 consecutive patients took part in the study. Life situation was measured
      through uncertainty in illness, satisfaction, and fear of the life situation.
      Descriptive statistics were used to present results, and analytical statistics
      were used to map out changes over time. Overall uncertainty showed a decrease
      over time. A statistically significant difference was found within the domain
      uncertainty related to information (P < 0.001). Satisfaction increased within the
      domains health-functioning, socio-economic, psychological-spiritual, and family.
      The ability to act within the domain health-functioning showed a statistical
      significance (P < 0.05). The domain life changes within fear in the life
      situation decreased and showed a statistical significance (P < 0.05). The overall
      life situation showed increased satisfaction as well as lower uncertainty and
      fear in the life situation. The research indicates that patients need more
      information about changes in the life situation after the implantable
      cardioverter defibrillator-implantation. The study encourages more humanistic,
      holistic research about patients' life situations as well as more education in
      teaching skills for health care personnel.

PMID- 11822505
TI  - Sexual problems in men with prostate cancer in comparison with men with benign
      prostatic hyperplasia and men from the general population.
AB  - In a questionnaire study, men with prostate cancer (n = 155) or benign prostatic
      hyperplasia (n = 131) identified more sexual problems than did men from the
      general population (n = 129). Sexual dysfunction was acknowledged regarding
      sexual pleasure and attraction, erectile function and sexual satisfaction and
      sexual performance. Lowered rates of sexual desire, pleasure and attraction were
      found when comparing their situation in recollection of pre-treatment situation
      to the current situation. Lower intercourse frequency and sexual satisfaction
      were also found. Medication, masturbation and artificial aids to achieve erection
      were not used as substitutes for shortcomings of erectile function either by men
      with prostate cancer and benign prostatic hyperplasia nor by their partners.
      There seemed to be a lack of information about the illness and treatment
      consequences for sexual life, including what physical dysfunction to expect after
      surgery and also what possible help to expect to compensate for the shortcomings.

PMID- 11822506
TI  - A grounded theory of nurse-client interactions in palliative care nursing.

PMID- 11822507
TI  - The threat of hypoglycaemia amongst Hong Kong Chinese patients: implications for
      clinical nursing practice.

PMID- 11822508
TI  - Nurse-patient partnerships in hospital care.

PMID- 11822509
TI  - Systematic reviews: gatekeepers of nursing knowledge.
AB  - The past few decades have seen a considerable increase in the number of available
      health care products and interventions. This growth has been matched by a similar
      expansion in the health care literature. As a result of these factors, the demand
      for evidence to support practice is growing, but finding the best evidence is
      becoming increasingly difficult. In response, the use of systematic reviews is
      increasing and they are starting to replace the primary research as the basis for
      health care decisions. To date, these reviews have focused predominantly on
      effectiveness and so have been limited to randomized controlled trials. As a
      result of this, the interpretive, observational and descriptive research methods
      that are utilized by nursing have commonly been either excluded from the review
      or are classified as 'low level' evidence. To address this, nursing must
      participate in the development of systematic review methods that better answer
      the questions posed by the profession.

PMID- 11822510
TI  - Protecting strategies used by sufferers of catastrophic illnesses and injuries.
AB  - The purpose of this research was to describe strategies used by sufferers of
      catastrophic illnesses and injuries. Participants were adult men and women with a
      variety of serious illnesses and injuries. Qualitative research approaches to
      data collection and data analysis, using grounded theory methods were employed.
      Descriptions of the participants indicate that several strategies are used; this
      discussion focuses on strategies to protect themselves from further suffering.
      Situations where participants use protecting strategies are identified and
      described. The findings indicate how care-recipients try to lessen the burden on
      their care-givers and to protect them from the stress of the sufferer's problems.

PMID- 11822512
TI  - Adherence to self-care and social support.
AB  - The purpose of the study reported in this paper was to describe adherence to self
      care, perceived difficulties and social support in a group of adult patients (n =
      213) with insulin-treated diabetes from two outpatient clinics in Northern
      Finland. Data were collected by questionnaire. The instruments were developed to
      measure adherence to self-care, difficulties in self-care and social support. The
      response rate was 76%. One-way ANOVA, logistic regression analysis, contingency
      and Pearson's correlation coefficients were used in the statistical analysis. A
      fifth of the respondents were neglecting their self-care. The others undertook
      flexible, regimen-adherent or self-planned self-care. The subjects had no
      difficulties with insulin treatment, but had more problems with other aspects of
      self-care. Poor metabolic control, smoking and living alone predicted neglect of
      self-care, but if patients had support from family and friends, living alone was
      not a predictor of neglect of self-care. Those with poor metabolic control
      perceived themselves as getting peer support from other persons with diabetes.

PMID- 11822511
TI  - Nutritional status, symptoms experienced and general state of health in HIV
      infected patients.
AB  - The aim of the study was to describe HIV-infected patients with respect to
      nutritional status, symptoms experienced, general state of health, and relevant
      medical and laboratory data. An additional aim was to study the relationships
      between some of these variables. On admission to an acute care hospital in
      Sweden, 25 HIV-positive men were consecutively included in the study. Medical
      data, anthropometric variables such as weight, height, body mass index (BMI) and
      percentage weight loss were studied. The following instruments were used: the
      subjective global assessment (SGA) was used to determine nutritional status; the
      oral assessment guide (OAG) was used for subjective assessment of the oral
      cavity; and the numeric rating scale (NRS) was used to assess the symptoms
      experienced. The Health Index (HI) was used to evaluate general state of health.
      The results showed that more than half of the patients had suspected/severe
      malnutrition; between 48% and 72% complained of moderate to severe symptoms of
      various kinds. Two thirds felt their general state of health was rather poor or
      very poor. Correlations showed that the lower the BMI, the worse the nutritional
      status (SGA); the greater the weight loss in percent, the worse the nutritional
      status (SGA); and the worse the general state of health (HI), the worse the
      nutritional status (SGA). In conclusion, it is important that nurses have good
      knowledge concerning nutritional problems in order to be able to detect these
      conditions at an early stage and/or to endeavour to prevent them.

PMID- 11822513
TI  - Consumer issues in navigating health care services for type I diabetes.
AB  - Despite increasing interest in consumer awareness and participation in health
      care service delivery, there has been little exploration of consumer views in
      relation to services for people with type I diabetes. The purpose of this
      qualitative exploratory study was to identify strategies people with type I
      diabetes used to access health services and the barriers they perceived in
      accessing the services they needed. Data gathered in semi-structured interviews
      revealed that consumers experience significant barriers when navigating the
      health care system. Three dominant themes were identified. They relate to access
      to specialist medical skill, to the transition from teenager to young adult and
      to pre-pregnancy and obstetric care. Directions for change in service delivery
      and policy development are discussed.

PMID- 11822514
TI  - Introducing an in-patient treatment for alcohol detoxification into a community
      setting.
AB  - Alcohol detoxification in the UK is not standardized and treatment is usually
      determined by local policies. Drug regimens are often predetermined and unrelated
      to the extent and duration of dependence, recent consumption, or previous
      withdrawal symptoms. Diazepam loading shortens the detoxification period and
      avoids the indiscriminate use of medication. It has been shown to be effective as
      an in-patient treatment. This paper examines the feasibility of introducing
      diazepam loading in a community setting, and discusses the implications that this
      would have for clinical practice.

PMID- 11822515
TI  - Communication issues for the interdisciplinary community palliative care team.
AB  - This paper discusses the findings of a critical study that examined the
      communication patterns between nurses and general practitioners (GPs) providing
      palliative care in Australia. Interviews and focus groups involved 40 palliative
      care nurses who worked in the three settings of care: community, hospice and
      hospital. Issues that impeded effective communication strategies between
      palliative care nurses and GPs were networking, case management, multiple service
      providers, lack of standardized documentation and formal tracking of clients,
      along with difficulties in transmission of relevant practice knowledge.
      Supporting strategies for effective formal modes of communicating and reporting
      are described.

PMID- 11822516
TI  - Caring for dying infants: experiences of neonatal intensive care nurses in Hong
      Kong.
AB  - Ten registered nurses working in a neonatal intensive care unit in Hong Kong were
      interviewed to explore their experiences of caring for infants whose disease is
      not responsive to curative treatment, their perceptions of palliative care, and
      factors influencing their care. Eight categories emerged from the content
      analysis of the interviews: disbelieving; feeling ambivalent and helpless;
      protecting emotional self; providing optimal physical care to the infant;
      providing emotional support to the family; expressing empathy; lack of knowledge
      and counselling skills; and conflicting values in care. The subtle cultural
      upbringing and socialization in nurse training and workplace environment also
      contributed to their moral distress. Hospital and nurse administrators should
      consider different ways of facilitating palliative care in their acute care
      settings. For example, by culture-specific death education, peer support groups,
      bereavement teams, modification of departmental policies, and a supportive work
      environment. Future research could include the identification of family needs and
      coping as well as ethical decision-making among nurses.

PMID- 11822517
TI  - Spiritual support for terminally ill patients: nursing staff assessments.
AB  - This study is part of a larger questionnaire survey concerned with the views of
      nursing staff on physical, emotional and spiritual support for terminally ill
      patients and decision making on the transition to the terminal phase of
      treatment. This article discusses the results concerning the spiritual support
      offered to terminally ill patients. The results describe the readiness and
      willingness of nursing staff to provide spiritual support, the expression of
      spiritual needs by patients, the provision of spiritual support, and problems
      occurring in providing this support. A total of 328 nurses working on the in
      patient wards of 32 community health centres took part. Data were collected with
      a questionnaire including both multiple choice items and open-ended questions.
      The data were processed with SPSS software and the responses to the open-ended
      questions were interpreted using content analysis. The results revealed
      shortcomings in nurses' readiness and willingness to provide spiritual support
      and clearly highlighted the need for further training. Half of the nurses said
      they only rarely offered spiritual support to their patients. The nurses drew
      attention to problems within themselves, their patients and with the availability
      of the chaplain's services. The results also pointed to factors related to the
      health centre and nursing staff.

PMID- 11822518
TI  - Nurses' experiences of research utilization within the framework of an
      educational programme.
AB  - This paper explores nurses' reflections on their experiences of disseminating and
      implementing research findings in clinical practice within the framework of an
      educational programme. Ten registered nurses, all in clinical practice,
      participated in a research-orientated educational programme with the aim of
      facilitating the dissemination and implementation of research findings in
      clinical practice. Thus, the programme contained different activities designed to
      disseminate and implement research findings in the participants' wards. Focus
      groups were used to collect data and a qualitative content analysis was
      performed. The main themes that were developed were: organizational and
      leadership issues; acquiring a new role; responses and reactions by others; and
      orientation to research. Organizational and leadership issues, nurses' interest
      in research, nurses' reading habits, and support and feedback from their head
      nurses and other managers and from their nursing colleagues and physicians were
      seen as important. This study confirms that research utilization and the change
      to research-based nursing practice are complex issues which require both
      organizational and educational efforts.

PMID- 11822520
TI  - Examining the validity of pressure ulcer risk assessment scales: developing and
      using illustrated patient simulations to collect the data.
AB  - Simulations are of particular advantage in research studies where large samples
      are necessary to achieve statistical power and the information must be collected
      under uniform conditions in order to aid interpretation. In the study reported
      below, simulation was achieved through the use of medical photography accompanied
      by case studies of the same patients. All information was collected on the same
      day. The purpose of the study was to determine the validity of the three pressure
      ulcer risk assessment scales most commonly used in clinical nursing practice in
      the UK. Each clinical nurse assessed the same four patients using three risk
      assessment scales and a visual analogue scale designed to capture their own
      clinical judgement. External validity was assessed by a panel of tissue viability
      experts who provided independent ratings. Data were obtained from 236 clinical
      nurses, yielding 941 risk assessments. Experience with this approach to data
      collection suggests that it requires careful planning. This should include
      measures to ensure that the simulated information is valid and that all data
      collectors have been adequately trained and are able to motivate the nurses
      participating in the study. Providing consideration is given to these issues, the
      use of simulation can help to collect data that would be difficult to obtain by
      more conventional means. It is also important to recognize that clinical
      decisions are de-contextualized in simulations because they are reduced to verbal
      and visual summaries. The decision to use simulations should thus be taken only
      if this is acknowledged.

PMID- 11822519
TI  - An evaluation of a teaching intervention to improve the practice of endotracheal
      suctioning in intensive care units.
AB  - Endotracheal suctioning is a frequently performed procedure that has many
      associated risks and complications. It is imperative that nurses are aware of
      these risks and are able to practise according to current research
      recommendations. This study was designed to examine to what extent intensive care
      nurses' knowledge and practice of endotracheal suctioning is based on research
      evidence, to investigate the relationships between knowledge and practice, and to
      evaluate the effectiveness of a research-based teaching programme. This quasi
      experimental study was a randomized, controlled, single-blinded comparison of two
      research-based teaching programmes, with 16 intensive care nurses, using non
      participant observation and a self-report questionnaire. Initial baseline data
      revealed a low level of knowledge for many participants, which was also reflected
      in practice, as suctioning was performed against many of the research
      recommendations. Following teaching, significant improvements were seen in both
      knowledge and practice. Four weeks later these differences were generally
      sustained, and provide evidence of the effectiveness of the educational
      intervention. The study raised concern about all aspects of endotracheal
      suctioning and highlighted the need for changes in nursing practice, with
      clinical guidelines and focused practice-based education.

PMID- 11822521
TI  - The dialysis diet and fluid non-adherence questionnaire: validity testing of a
      self-report instrument for clinical practice.
AB  - This study evaluated the validity of the dialysis diet and fluid non-adherence
      questionnaire (DDFQ) as a self-report instrument for clinical practice. The DDFQ
      was designed to measure non-adherence behaviour with diet and fluid guidelines in
      patients treated with hospital-based haemodialysis in Flanders (Belgium). In a
      multicentre cross-sectional study design, 564 patients from 10 dialysis centres
      in Flanders completed the DDFQ Criterion and construct validity of the instrument
      were substantiated using correlation techniques between the DDFQ and biochemical
      and biological ratings of non-adherence. The results of this study suggest that
      the DDFQ is a valid self-report instrument to assess non-adherence behaviour in
      haemodialysis patients in Flanders and probably also in other cultures.

PMID- 11822522
TI  - The effect of health assessments by practice nurses on uptake of influenza
      vaccination among older people in the UK.

PMID- 11822523
TI  - Minority health risk behaviors: an introduction to research on sexually
      transmitted diseases, violence, pregnancy prevention and substance use.
AB  - AIMS: The goal of this article is to introduce the Research on Sexually
      Transmitted Diseases, Violence, and Pregnancy Prevention Project (RSVPP), which
      represents one response of the National Institutes of Health to reduce health
      disparities in racial and ethnic populations. METHODS: As part of this effort,
      seven independent projects were funded to design, implement, and evaluate
      community-based intervention strategies aimed at reducing risk behaviors among
      minority youth. The interventions and research designs varied across the sites;
      however, all sites included a common set of questions in their questionnaires.
      This study focuses on the lessons learned about community-based research across
      all sites. RESULTS: Sites learned many lessons regarding community-based
      research, including: the value of building trust, the dynamic nature of
      communities, the intensive time and resources necessary for success,
      dissimilarities between researcher and community goals, the value of clear
      communication, the importance of recognizing the contribution of community
      members and expressing gratitude for their efforts; the difficulty of
      disseminating findings regarding sensitive topics, and the need for continuation
      of interventions. CONCLUSION: Community involvement posed challenges, but
      enhanced the quality of the implementation and the evaluation of the
      interventions. This special issue includes findings from the RSVPP sites.

PMID- 11822524
TI  - Violent behaviors in early adolescent minority youth: results from a "middle
      school youth risk behavior survey".
AB  - OBJECTIVES: To describe the prevalence and characteristics of violence and
      violence-related behaviors among six populations of U.S. minority adolescents in
      grades 6-8. METHODS: Six thousand four hundred non-White adolescents were
      recruited from six sites that were part of a collaborative project. Surveys were
      administered either during the school day or at community facilities. All
      students at each site were asked 10 questions about recent violence-related
      behaviors (including use of threats, fighting, weapon carrying, and weapon use).
      Prevalence of each violence-related behavior was reported within and across
      sites, and stratified by race/ethnicity, gender, age, and other characteristics
      expected to influence the behaviors. RESULTS: Sixty-six percent (66%) of the
      middle school students sampled reported being involved in some type of recent
      fighting and/or weapon-related behaviors. Sixty-one percent (61%) indicated some
      form of fighting behavior in the past 3 months (threatening to beat someone up,
      physical fighting, and/or being hurt in a fight). Thirty percent (30%) of
      participating youth reported one or more weapon-related behaviors (threatening to
      use a weapon, carrying a weapon, using a weapon, and/or being cut, stabbed or
      shot at). Reported gun carrying among males varied depending upon site, but was
      as high as 20%. Grade in school was positively associated with reported violent
      behaviors. Adolescents who reported living full-time with a parent or parent
      figure, and those who reported religious observance or beliefs, were less likely
      to report violence involvement. All violence-related behaviors were more common
      among male than female adolescents. CONCLUSIONS: Violence prevention efforts
      should begin in elementary school and continue throughout adolescence. Programs
      should be prepared to provide services or referrals to victims of violence,
      implement programs tailored toward females as well as males, and build
      partnerships with churches and other community organizations in which youth are
      involved.

PMID- 11822525
TI  - Hopelessness and violence among inner-city youths.
AB  - OBJECTIVES: Ethnographic literature on inner-city life argues that adolescents
      react to their uncertain (and objectively bleak) future by abandoning hope; this,
      in turn, leads them to engage in risk behaviors, including violence, with
      considerable frequency. This study empirically measures the pervasiveness of
      hopelessness and uncertainty about the future among inner-city adolescents and
      documents the link between hopelessness, uncertainty, and risk behavior. METHODS:
      We surveyed a sample of 583 adolescents (aged 9-19) living in public housing in
      Huntsville, AL; this constitutes 80% of the eligible population. Each participant
      in the survey received $10. Their responses yielded empirical distributions for
      hopelessness, uncertainty about the future, and four violent behaviors. Using OLS
      regression, we examined the effect of hopelessness on these violent behaviors.
      RESULTS: Hopelessness about the future was relatively rare, affecting only 20-30%
      of the respondents. However, it was a strong predictor of fighting and carrying a
      knife for females, and of carrying a knife, carrying a gun, and pulling a knife
      or gun on someone else for males. Uncertainty about the future was more
      prevalent, but unrelated to the violent behaviors. CONCLUSIONS: These results
      suggest that the conclusions of the ethnographic literature are only partially
      valid: While hopelessness is, in fact, strongly related to risk behavior, it is
      not nearly so prevalent as is generally assumed.

PMID- 11822526
TI  - The protective influence of parents and peers in violence avoidance among African
      American youth.
AB  - OBJECTIVES: This study attempted to provide further insight into the roles of
      parents and peers as they influence youth involvement with violence.
      Specifically, this paper considers whether parents who are close to their
      children have children who affiliate with prosocial friends who may in turn serve
      as a buffer against violence. This study also considers how parent and peer
      influences may change as youth transition to adolescence. METHODS: A cross
      sectional health behavior survey was administered to 384 low-income, African
      American youth aged 10-15 from three Chicago area schools. Structural equation
      models (SEM) were developed to assess the impact of youth reported prosocial
      friends and parental closeness on violence involvement. The overall model was
      tested to examine equivalence across preadolescent and adolescent age-groupings.
      RESULTS: Results from the overall model indicated that parental closeness did not
      have a direct influence on youth violence involvement, but having a close parent
      child relationship improved the youth's ability to select prosocial friends,
      which was directly related to decreased involvement with violence. Differences in
      the model by age-grouping suggested the presence of prosocial friends was a
      stronger factor for adolescent violence avoidance when compared to
      preadolescents. CONCLUSIONS: Parents can make a difference in the way in which
      their children choose their friends and therefore get involved with violence by
      maintaining a closely bonded relationship throughout preadolescence and
      adolescence. The importance of this closely bonded relationship has even greater
      effects for decreasing violence involvement for adolescents than preadolescents.

PMID- 11822527
TI  - The theory of planned behavior as a model of intentions for fighting among
      African American and Latino adolescents.
AB  - OBJECTIVES: To test the theory of planned behavior as a model for predicting and
      understanding behavioral intentions for fighting among inner-city adolescents and
      to determine whether its predictive power differs as a function of ethnicity
      (African American versus Latino). METHODS: Participants were 956 (511 females,
      445 males) African American (n = 702) and Latino (n = 254) adolescents (mean age
      = 12.72 years; SD = 1.12) recruited from sixth, seventh, and eighth grade classes
      in public middle schools serving two inner-city communities in New Jersey who
      completed self-administered, confidential questionnaires. RESULTS: Consistent
      with the theory of planned behavior, hierarchical multiple regression analyses
      revealed that attitudes, subjective norms, and perceived behavioral control
      predicted intentions for fighting. Although the theory of planned behavior
      accounted for substantial variance in intentions to fight in both ethnic groups,
      it accounted for greater variance among Latinos than among African Americans. The
      strength of the relations of subjective norms and perceived behavioral control to
      intentions was similar in the two groups. but the relation of attitudes to
      intentions to fight was significantly stronger among Latinos. CONCLUSIONS: The
      findings strongly suggest that the theory of planned behavior provides a
      potentially useful conceptual framework for guiding the creation of interventions
      for African American and Latino adolescents that are designed to reduce violent
      behavior and the tragedies that such behavior leaves in its wake.

PMID- 11822528
TI  - Gender attitudes and health risk behaviors in urban African American and Latino
      early adolescents.
AB  - OBJECTIVES: This study examines the association of beliefs about gender
      differences (frequently termed gender attitudes or attitudes about women in other
      research) and of beliefs specifically about masculinity to health risk behaviors
      in minority, urban, early adolescents, in light of the "gender conventionality"
      hypothesis. METHODS: Data from a self-administered questionnaire assessing gender
      attitudes and violence-related, substance use, and heterosexual health risk
      behaviors administered to 587 African American and Latino early adolescents are
      analyzed. RESULTS: With sociodemographic and family variables controlled, in
      males violence-related behaviors and substance use are associated with
      traditional beliefs about masculinity, and heterosexual activity is associated
      with traditional beliefs about gender differences. In females, being sexually
      active is positively associated with traditional beliefs about masculinity.
      CONCLUSIONS: Interventions to reduce health risk behaviors in minority, urban,
      early adolescents may be more effective if they include greater attention to ways
      in which gender-related attitudes may play a role in health risk taking.

PMID- 11822529
TI  - Protective factors associated with American Indian adolescents' safer sexual
      patterns.
AB  - OBJECTIVES: This paper presents findings from a research partnership with rural
      American Indian communities to identify protective factors associated with their
      adolescents' health-related behaviors including 1) delay of sexual debut; 2) not
      having had intercourse in the past 3 months; 3) birth control use among sexually
      active adolescents in the past 3 months; 4) condom use in the past 3 months. Our
      goal was to identify salient characteristics of students and their perceptions of
      family, school, and friends which could be incorporated or supported in future
      program planning for adolescents. METHODS: A written survey was administered to
      484 Indian students in Grades 6-12 from five rural schools. The survey measured
      several potential protective factors identified by Problem Behavior Theory, along
      with self-efficacy and cultural interest and knowledge. Logistic regression
      assessed the relationship of the protective factors and positive sexual
      behaviors. RESULTS: Factors significantly associated with abstention from
      intercourse and/or consistent use of birth control included perceived lower
      health-risk behavior of friends, higher perceived parental support, higher
      perceived parental knowledge and monitoring of the adolescent's activities and
      friends, a higher value on scholastic achievement, higher reported academic
      performance, and higher self-efficacy for safer sexual behaviors. CONCLUSIONS:
      This research suggests that Indian adolescents have several protective factors
      indigenous to their communities which are modifiable. Building on the unique
      cultural heritage of Indian communities, many of these factors may be addressed
      through community planned prevention programs.

PMID- 11822531
TI  - Genetic factors in hypertension--what is known and what does it mean?

PMID- 11822530
TI  - From the perspective of an NIH program officer: observations on RSVPP.

PMID- 11822532
TI  - Home blood pressure monitoring. Current knowledge and directions for future
      research.
AB  - Home blood pressure (BP) monitoring has become popular in clinical practice and
      several automated devices for home BP measurement are now recommendable. Home BP
      is generally lower than clinic BP, and similar to daytime ambulatory BP. Home BP
      measurement eliminates the white coat effect and provides a high number of
      readings, and it is considered more accurate and reproducible than clinic BP. It
      can improve the sensitivity and statistical power of clinical drug trials and may
      have a higher prognostic value than clinic BP. Home monitoring may improve
      compliance and BP control, and reduce costs of hypertension management.
      Diagnostic thresholds and treatment target values for home BP remain to be
      established by longitudinal studies. Until then, home BP monitoring is to be
      considered a supplement. However, high home BP may support or confirm the
      diagnosis made in the doctor's office, and low home BP may warrant ambulatory BP
      monitoring. During long-term follow-up, home BP monitoring provides an
      opportunity for close attention to BP levels and variations. The first
      international guidelines have established a consensus document with
      recommendations, including a proposal of preliminary diagnostic thresholds, but
      further research is needed to define the precise role of home BP monitoring in
      clinical practice.

PMID- 11822533
TI  - Hypertensive left ventricular hypertrophy: pathophysiological and clinical
      issues.

PMID- 11822534
TI  - The older hypertensive.
AB  - In this review the hypertensive status in older subjects is briefly examined from
      a diversity of angles: epidemiological/semiotic; pathophysiological (including
      haemodynamic/vascular, renal and neurohormonal features); components of blood
      pressure as separate cardiovascular risk factors in their own right, results of
      randomized trials comparing active with placebo treatment and comparing different
      active regimens (including diabetics as a subgroup with excessive risk); and,
      finally, modalities of treatment with a view on quality of life.

PMID- 11822535
TI  - Diabetes and hypertension.
AB  - The incidence of hypertension is increased in individuals with diabetes mellitus.
      This is especially true in patients with type 2 diabetes. In these patients high
      blood pressure is common at the time of diagnosis of diabetes, but the
      development of diabetes is often preceded by a period during which
      hyperinsulinemia and insulin resistance is already present. Diabetes represents
      by itself a major risk of cardiovascular morbidity and mortality. This risk is
      considerably enhanced by the co-existence of hypertension. One of the main
      complications of type 2 diabetes is nephropathy, which manifests initially by
      microalbuminuria, then by clinical proteinuria, leading to a progressive chronic
      renal failure and end-stage renal disease. Microalbuminuria is considered today
      as an indicator of renal endothelial dysfunction as well as an independent
      predictor of the cardiovascular risk. During recent years a number of studies
      have shown that tight blood pressure control is essential in diabetic patients in
      order to provide maximal protection against cardiovascular events and the
      deterioration of renal function. Of note, there is recent evidence indicating
      that blockade of the renin-angiotensin system with angiotensin II antagonists has
      marked nephroprotective effects in patients with hypertension and type 2
      diabetes, both at early and late stages of renal disease.

PMID- 11822536
TI  - Renal participation in cardiovascular risk in essential hypertension.
AB  - Renal damage as a consequence of uncontrolled hypertension is well recognized.
      Antihypertensive therapy has been proved to significantly decrease the vascular
      damage in the kidneys of hypertensive patients. However, prevalence of mild renal
      insufficiency remains present in a significant proportion of the hypertensive
      population. This is accompanied by a marked increase in cardiovascular risk, as a
      consequence of the clustering of other cardiovascular risk factors and of
      insufficiently controlled blood pressure. Prevention and protection of renal and
      cardiovascular damage in these patients will be one of the most relevant healt
      care tasks in the future.

PMID- 11822537
TI  - The renin-angiotensin system in the twenty-first century.

PMID- 11822538
TI  - Challenges for the prevention of primary and secondary stroke: the importance of
      lowering blood pressure and total cardiovascular risk.
AB  - It is well established that blood pressure lowering is effective for the primary
      prevention of stroke and other cardiovascular disorders in subjects with blood
      pressures as low as 140/90 mmHg, and up to 80 years of age. Despite this
      knowledge, blood pressure levels are controlled in less than 25% of the
      hypertensive population worldwide. It has taken longer to prove that blood
      pressure lowering is equally effective for the prevention of recurrent stroke.
      The results of PROGRESS (Perindopril Protection Against Recurrent Stroke Study)
      have confirmed that a perindopril-based regimen in subjects with cerebrovascular
      disease substantially reduces the incidence of secondary stroke and primary
      myocardial infarction. It is daunting to recall that it has taken almost two
      decades for beta-blockers to be widely used for the secondary prevention of
      myocardial infarction, since widespread use of the PROGRESS regimen would prevent
      more than half a million strokes worldwide each year. The real challenge now is
      to implement novel and effective strategies for the control of blood pressure and
      other cardiovascular risk factors worldwide. Strategies should include lifestyle
      measures, such as stopping smoking, exercise and reducing overweight. There is a
      real need to identify hypertensive subjects and treat them with blood pressure
      lowering drugs for primary prevention. In subjects with established
      cardiovascular disease, consideration should be given to a range of proven
      interventions for secondary prevention, such as blood pressure lowering,
      irrespective of current blood pressure, anti-platelet drugs, statins for lowering
      cholesterol and glycaemic control in diabetics. Among new strategies to lower
      overall cardiovascular risk, consideration should be given to the development of
      single-pill combinations of drugs of known efficacy, including various
      combinations of ACE inhibitors, diuretics, beta-blockers, aspirin and statins,
      among others.

PMID- 11822539
TI  - Non pharmacologic therapy and lifestyle factors in hypertension.
AB  - Lifestyle factors are now recognised to be key determinants of both the rise in
      blood pressure with ageing and the cardiovascular disease associated with
      essential hypertension. This paper summarises recent evidence for independent or
      additive effects of different aspects of diet and behavioural factors on blood
      pressure levels and some related cardiovascular risk factors. The influence of
      single nutrients, fats, fibre, protein, antioxidants, caffeine, complex dietary
      patterns, physical activity, alcohol and smoking will be considered against a
      background of obesity and psychological factors contributing to blood pressure
      elevation.

PMID- 11822540
TI  - Beta-adrenergic blocking drugs in the treatment of hypertension.
AB  - The reduction in blood pressure seen with the use of beta-blocking drugs was an
      unexpected finding. Initially there was resistance to their use as the reduction
      of cardiac output and increase in peripheral resistance from beta-blockade was
      considered an undesirable pharmacological action for a drug in the treatment of
      hypertension. However, beta-blockers have now become established in the treatment
      of hypertension and have been recommended as a first line choice in various
      guidelines, although their exact mode of action remains a matter for debate. In
      broad terms beta-blocking drugs are at least of similar efficacy to the other
      major classes of antihypertensive drugs. They may be usefully combined with other
      anti-hypertensives, as is often required. There is some evidence that the beta-1
      selective agents are more efficacious than the non-selective beta-blockers.
      Notwithstanding some observations to the contrary beta-blockers are often
      effective antihypertensive agents in the elderly and in black patients; the
      combination of being elderly and black, however, appears to result in a reduced
      fall in blood pressure. If they are given early in pregnancy they lead to a low
      birth weight. Co-existant disease may influence the choice of a beta-blocker to
      treat hypertension. Beta-blockers are valuable agents in ischaemic heart disease,
      notably the control of chronic angina pectoris and to improve prognosis post
      myocardial infarction. While initial dose titration has to be extremely careful,
      heart failure is now a strong indication for the use of a beta-blocker, as
      prognosis is much improved. Diabetes should no longer be regarded as a contra
      indication to the use of a beta-1 selective agent. Recent work confirms that beta
      blockers should be given to patients undergoing surgery who have a high cardiac
      risk. Outcome studies suggest overall that in younger patients beta-blockers
      reduce the incidence of strokes and myocardial infarction. There is no convincing
      evidence of a difference between the ACE inhibitor captopril and the combination
      of diuretic and a beta-blocker. In high risk patients, i.e. those with diabetes,
      no difference was seen between captopril and atenolol. Diuretics may result in
      better outcome measurements in the elderly compared to beta-blockade but in
      combination, "conventional treatment" is as effective in terms of total
      mortality, strokes and myocardial infarction as ACE inhibitors or calcium
      antagonists. Co-existant asthma remains an important contraindication to beta
      blockade, but not chronic obstructive airways disease where a beta-blocker should
      be used with caution if it is indicated, e.g. post-infarction. Quality of life
      measurements, at least with beta-1 selective agents compare favourably with other
      anti-hypertensive drugs. Beta-blockers, without partial agonist activity, should
      not be stopped abruptly, particularly in patients with, or at high risk of, co
      existant ischaemic disease because of the danger of post-beta-blockade cardiac
      sympathetic hypersensitivity; alternatively bed rest should be instituted to
      reduce the risk of sympathetic stimulation.

PMID- 11822541
TI  - Calcium antagonists in hypertension.

PMID- 11822542
TI  - How to handle renovascular hypertension.

PMID- 11822543
TI  - From chaos to chaos. An analysis of a discrete age-structured prey-predator
      model.
AB  - Discrete age-structured density-dependent one-population models and discrete age
      structured density-dependent prey-predator models are considered. Regarding the
      former, we present formal proofs of the nature of bifurcations involved as well
      as presenting some new results about the dynamics in unstable and chaotic
      parameter regions. Regarding the latter, we show that increased predation may act
      both as a stabilizing and a destabilizing effect. Moreover, we find that possible
      periodic dynamics of low period, either exact or approximate, may not be
      generated by the predator, but it may be generated by the prey. Finally, what is
      most interesting from the biological point of view, is that given that the prey,
      in absence of the predator, exhibits periodic or almost periodic oscillations of
      low period, then the introduction of the predator does not alter this periodicity
      in any substantial way until the stabilizing effect of increased predation
      becomes so strong that a stable equilibrium is achieved.

PMID- 11822544
TI  - The evolution of dispersal rates in a heterogeneous time-periodic environment.
AB  - A reaction-diffusion model for the evolution of dispersal rates is considered in
      which there is both spatial heterogeneity and temporal periodicity. The model is
      restricted to two phenotypes because of technical difficulties, but a wide range
      of mathematical techniques and computational effort are needed to obtain useful
      answers. We find that the question of selection is a great deal richer than in
      the autonomous case, where the phenotype with the lowest diffusion is selected
      for. In the current model either the lower or higher diffuser rate may be
      selected, or there may be coexistence of phenotypes. The paper raises several
      open questions and suggests in particular that a mutation-selection multi
      phenotypic model would repay study.

PMID- 11822545
TI  - Does increased stochasticity speed up extinction?
AB  - We consider the impact of increased stochastic fluctuations on the extinction
      date of an unstructured population subject to either environmental or
      demographical stochasticity (or both). By modelling the population density as a
      general linear diffusion, we state a set of typically satisfied conditions under
      which the decreasing minimal r-excessive mapping (and, therefore, the moment
      generating function) of the considered diffusion process is convex and,
      consequently, under which the impact of increased stochastic fluctuations on the
      expected date at which the density becomes arbitrarily small is unambiguously
      negative. In other words, we establish a set of sufficient conditions under which
      increased stochasticity speeds up the extinction process independently of whether
      stochasticity is environmental or demographic. In this way, we are able to
      confirm that increased stochasticity is detrimental for population growth.

PMID- 11822546
TI  - On fitness in structured metapopulations.
AB  - In this paper we derive a general expression measuring fitness in general
      structured metapopulation models. We apply the theory to a model structured by
      local population size and in which local dynamics is explicitly modelled. In
      particular, we calculate the evolutionarily stable dispersal strategy for
      individuals that can assess the local population density in the case where only
      dispersal is subject to evolutionary control but all other model in gredients are
      assumed fixed. We show that there exists a threshold size such that at ESS
      everyone should stay as long as the population size is below the threshold and
      everyone should disperse immediately as the population size reaches the
      threshold.

PMID- 11822547
TI  - Predator migration in response to prey density: what are the consequences?
AB  - A predator-prey metapopulation model with two identical patches and only
      migration of the predator is investigated. Local predator-prey interaction is
      described by the so-called Rosenzweig-MacArthur model, while the migration term
      of the predator is put in a nonlinear form, which is derived by extending the
      Holling time budget argument to migration. In particular, a dimensionless
      parameter theta is introduced to quantify the migration tendency of predators
      while they are handling their prey, which gives rise to a family of models
      connecting two extremes: predators have no inclination to migrate while handling
      prey (theta = 0) and standard diffusion (theta = 1). Various aspects of the
      model, including changes in the number and the stability of equilibria and limit
      cycles, are investigated. We then focus on the key question: "Does spatial
      structure lead to a substantial damping of the violent oscillations exhibited by
      many predator-prey models?". It is known that the answer is "yes" if one adopts
      standard diffusion (theta = 1). However, we present substantial evidence that the
      answer is "no" if one takes theta = 0. We conclude that the migration submodel is
      an important constituent of a spatial predator-prey model and that the issue
      deserves scrutiny, both experimentally and theoretically.

PMID- 11822548
TI  - Keepin' it R.E.A.L.!: program description and results of baseline assessment.
AB  - In this article, the authors present the results of the analysis of the baseline
      data from Keepin' it R.E.A.L.!, an HIV prevention project developed for mothers
      and their adolescents. Six hundred twelve mostly male (60.6%) and African
      American (98.2%) adolescents completed baseline assessments. Eleven percent of
      the adolescent participants reported initiating sexual intercourse. Adolescent
      participants expressing higher levels of self-efficacy to resist peer pressure,
      more favorable outcome expectancies, less communication about sex with their
      mothers, higher levels of self-concept related to their behavior, lower levels of
      self-concept related to popularity, and less stress reported fewer types of
      intimate sexual behaviors. Adolescent participants who reported higher self
      efficacy to resist peer pressure to have sex and lower levels of stress were less
      likely to have initiated sexual intercourse. Selected characteristics of mothers
      did not contribute to understanding factors associated with intimate sexual
      behaviors or initiation of sexual intercourse among adolescent participants.

PMID- 11822549
TI  - Consumers' understanding of the Dietary Guidelines for Americans: insights into
      the future.
AB  - The purpose of this study was to examine consumers' knowledge and understanding
      of the 1995 Dietary Guidelines for Americans and the sources from where consumers
      obtain their health information. A telephone survey was administered to 400
      adults in the Twin Cities area in Minnesota. The number of guideline
      recommendations recalled per person was, on average, less than 2.5 of a total of
      13 recommendations. Participants had difficulties interpreting the guidelines.
      Knowledge of the dietary fat guideline was especially poor. Only 17% of survey
      participants correctly stated the amount of total fat they should have in their
      diet. The total number of media sources used to obtain health information was the
      variable that best explained the variance in knowledge of the Dietary Guidelines
      recommendations. To effectively change dietary behavior, health educators must
      work effectively with the media to develop behavior-focused nutrition messages
      that are meaningful and clear to consumers.

PMID- 11822550
TI  - Ethical dilemmas in participatory action research: a case study from the
      disability community.
AB  - Participatory action research (PAR) is a collaborative approach to inquiry for
      education and social change that is gaining increasing prominence in health
      education. This case study explores the use of PAR by and with a community of
      people with disabilities in addressing a polarizing issue in that community:
      death with dignity or physician-assisted suicide legislation. Following a brief
      review of the debate within the community about this issue and the goals,
      methods, and findings of this project, the authors examine four key ethical
      challenges. These are dilemmas in issue selection when the community is deeply
      divided over a problem area, inclusion and exclusion in study team makeup and
      sample selection, insider/outsider issues, and how best to use findings in ways
      that can unite and strengthen the community. The implications of these issues for
      health educators and others engaged in community-based PAR efforts are presented.

PMID- 11822551
TI  - Ethical dilemmas created by the criminalization of status behaviors: case
      examples from ethnographic field research with injection drug users.
AB  - The criminalization of behaviors such as the ingestion of certain mood-altering
      drugs creates ethical dilemmas for researchers studying those behaviors. The
      Syringe Access, Use, and Discard (SAUD) project is designed to uncover
      microcontextual factors that influence HIV and hepatitis risk behaviors of
      injection drug users. The article presents seven ethical dilemmas encountered
      using ethnographic methods: issues involving syringe replacement at injection
      locales, risks of participants' arrest, potential disruptions in participants'
      supply routes, risks of research staff arrest, threats to the protection of
      confidentiality, issues surrounding informed consent in working with addicts, and
      the confiscation of potentially incriminating information by police. The article
      concludes with a discussion of the limitations of traditional ethical frameworks,
      such as utilitarianism, for resolving these dilemmas and recommends instead
      improving public health professionals' capacity for practical reasoning
      (phronesis) through the greater use of case studies in public health curricula.

PMID- 11822552
TI  - Ethics instruction in an issues-oriented course on public health genetics.
AB  - Public health ethics and genetics in public health have in the last decade
      emerged as fields in their own right. This article describes the ethics component
      of an "Issues in Public Health Genetics" course uniting the fields of genetics,
      ethics, and public health. As the third member of the University of Michigan
      Interdepartmental Concentration in Genetics, the course emphasizes the
      translation of ethical-social issues into substantive policies. A central tension
      repeated throughout the course exists between respect for individuals'
      libertarian interests and the welfare of the entire population. Students become
      familiar with the process of resolving conflicting values through interactive
      exercises addressing the health needs of diverse communities. Key lessons in
      course design are described.

PMID- 11822553
TI  - Breastfeeding and sexuality: professional advice literature from the 1970s to the
      present.
AB  - Since the 1970s, there has been a trend on the part of physicians and other
      health practitioners to promote breastfeeding in the United States, a movement
      that has not been as successful as hoped, since the majority of mothers in this
      country continue to feed their babies formula. Several socioeconomic factors are
      considered to be barriers to the success of breastfeeding promotion today. Yet,
      even among those who promote breastfeeding there exists a notable constraint in
      dealing with the issue of sexuality and breastfeeding. Indeed, as the female
      breast is eroticized in Western society, breastfeeding promotional messages have
      often exhibited a tacit conformity to social conventions regarding female
      sexuality. When analyzing selected works of advice literature written by health
      care practitioners from the 1970s to the present, it will be clear that
      breastfeeding promotional information often reflects dominant views of the
      sexuality of the female breast and her body.

PMID- 11822554
TI  - Teen driving risk: the promise of parental influence and public policy.
AB  - An analysis is presented of adolescent driving risk, the advantages of graduated
      licensing programs, and the potential for parent-based programs to moderate teen
      driving risks. Risk factors associated with youthful driving illustrate the
      potential importance and benefits of limiting the amount and conditions under
      which teens can drive. State policies, such as graduated driver licensing systems
      that formalize restrictions on youthful driving. have been shown to be effective.
      However, teen driving risks remain elevated. Parents are in a prime position to
      extend the benefits of state restrictions by developing and implementing their
      own tailored family policies on adolescent driving. Unfortunately, parents of
      adolescent drivers are often under-aware of the need to do so and fail to impose
      effective driving restrictions. An ongoing parent-based intervention to increase
      parental restriction on teen driving is described, and issues involved in
      implementing and evaluating family-centered approaches to reduce teen driving
      risk are raised.

PMID- 11822556
TI  - A comment on terrorism.

PMID- 11822555
TI  - Estimates of intragroup dependence for drug use and skill measures in school
      based drug abuse prevention trials: an empirical study of three independent
      samples.
AB  - Group-randomized drug abuse prevention trials customarily designate schools as
      the unit of assignment to experimental condition; however, students within
      schools remain the unit of observation. Students nested within schools may show
      some resemblance based on common (peer) selection or school climate factors
      (i.e., disciplinary practices, group norms, or rules). Appropriate analyses of
      any treatment effects must be statistically correct for the magnitude of
      clustering within these intact social units (i.e., intraclass correlation
      coefficient [ICC]). There is little reported evidence, however, of variation in
      ICCs that might occur with studies of racially or geographically diverse
      populations. The purpose of this study was to generate estimates of intragroup
      dependence for drug use and psychosocial measures (hypothesized mediators) from
      three separate drug abuse prevention trials. Clustering for the drug use measures
      averaged .02 across study and age-groups (range = .002 to .053) and was
      equivalently small for the psychosocial measures (averaging .03 across studies
      and age-groups; range = .001 to .149). With few exceptions and across different
      samples, clustering decreased in magnitude over time. Clustering was largest for
      peer smoking and drinking norms among white, suburban youth and smallest for
      alcohol expectancies among urban black youth. Findings are discussed with respect
      to the influence of social climate factors and group norms in the design and
      analysis of school-based, drug abuse, prevention programs.

PMID- 11822557
TI  - Weighing the cons and pros: women's reasons for discontinuing hormone replacement
      therapy.
AB  - As a greater proportion of U.S. women move into midlife, there has been increased
      interest in meeting their preventive health needs. Although hormone replacement
      therapy (HRT) may not be an option for all postmenopausal women, it has been
      documented as prolonging life expectancy and protecting against osteoporosis.
      Despite its advantages for many women, often those who initiate HRT discontinue
      its use within a short time. The purpose of this qualitative study is to gain
      insights into women's reasons for discontinuing HRT. We collected data by
      semistructured interview from three diverse samples: 10 women who had been on HRT
      for two years or less, 11 health care providers of women, and 34 women who had
      gone off HRT. Reasons for discontinuing fell into seven broad categories: general
      Gestalt, somatic complaints, mind (knowledge, emotion), not being heard, hassles,
      indecisive medical community, and cons outweighed pros. Results indicate that
      women who discontinue HRT do so for a variety of reasons, many of which are
      connected to the health care system and its providers. Outcomes also suggest that
      sharing in decision making along with increased education, support, and
      individualized care are necessary to better address the preventive health care
      needs of postmenopausal women.

PMID- 11822558
TI  - Infant feeding practices: the case of Hmong women in Australia.
AB  - I discuss infant feeding beliefs and practices among Hmong women in Melbourne,
      focusing particularly on changed patterns that have occurred since their
      settlement in Australia. Traditionally, Hmong women breastfeed their newborn
      infants. Most women can breastfeed successfully in their homeland. However, since
      their settlement in a new country, some women have changed to bottlefeeding.
      Reasons given include the need to study English and seek employment, the
      availability of infant formula, insufficient milk, and their concern about the
      health and well-being of the infants. Hmong women either choose breast- or
      bottlefeeding based on what they think is best for their babies; their clear
      intention is to have children who will be healthy and thrive. Understanding of
      women's beliefs and practices relating to feeding is essential in creating a
      breastfeeding campaign. More importantly, the information will assist health
      professionals to support mothers in their choice of a feeding method, whether it
      be breast or bottle.

PMID- 11822559
TI  - Exploring health promoting lifestyle behaviors of Japanese college women:
      perceptions, practices, and issues.
AB  - The purpose of this study was to explore health promoting lifestyle behaviors
      (HPLBs) of college women in Japan. In addition, perceived health status and
      concerns were evaluated. The methods used were both qualitative and quantitative.
      The qualitative data from focus groups with 38 Japanese college women were used
      to develop a questionnaire. Subsequently, 546 randomly selected college women
      responded to the mailed survey (response rate 54%). Forty percent of the college
      women respondents perceived themselves as "rather unhealthy" or "unhealthy." The
      investigator conclude that (1) perceived HPLBs, health status, and health
      concerns were mutually associated, thus, to increase perceived health status
      and/or decrease perceived health concerns, promoting healthy lifestyle behaviors
      must be considered; (2) the number of perceived motives or cues and the number of
      perceived health concerns of importance to college women must be considered to
      promote healthy lifestyle behaviors.

PMID- 11822560
TI  - Factors that support women's successful transition to the community following
      jail/prison.
AB  - The purpose of this study was to describe factors that support women's successful
      transition to the community following incarceration. The design is qualitative,
      utilizing open-ended data generating interview questions of women who participate
      in Welcome Home Ministries (WHM), a new community faith-based program for women
      released from jail/prison. A multitude of factors are necessary to support
      women's successful transition to the community following incarceration. Although
      no questions were asked about religion or spirituality, the rank-ordered dominant
      factors were a spiritual belief and practice and freedom from addiction. The role
      of support groups and their "sisters" in WHM, the nurse-chaplain's jail visit and
      support, and the role of supportive friends (not former drug using friends) were
      additional key factors. The study findings may be used to support the design of
      new interventions based upon women's needs and capacities to empower them to
      create their own and their children's healthy future.

PMID- 11822561
TI  - Problems experienced by pregnant student nurses in the Republic of South Africa.
AB  - The purpose of this quantitative exploratory descriptive survey was to determine
      which problems pregnant student nurses experienced in the Northern Province (NP)
      of the Republic of South Africa (RSA). Questionnaires were completed by 93
      pregnant student nurses in this province, indicating that the majority of them
      became pregnant because they lacked knowledge about contraceptives, emergency
      contraceptives, and termination of pregnancy (TOP) services (legalized in the RSA
      since 1996). They delayed seeking prenatal care and experienced tiredness,
      dizziness, and vaginal bleeding during the first trimester. Most pregnant student
      nurses encountered academic problems as a result of their pregnancies. These and
      other results indicate a dire need to educate the student nurses about
      contraceptives and about accessing reproductive health care services. If the
      students do not utilize the available services themselves, it is unlikely that
      they will advise their clients to utilize such services.

PMID- 11822562
TI  - Women-centred care: working collaboratively to develop gender inclusive health
      policy.
AB  - We argue that policies for women-centred care ought to be developed to address
      the inadequacy of the current health system to recognize that women are affected
      differently by health policies and programs and that gender is a determinant of
      health; furthermore, such policies must be created with representatives from
      relevant health professional organizations so that the policies are translated
      and operationalized at the organizational and practice level. A collaborative
      research process, co-operative inquiry, was used to conduct the research. This
      process engages the participants in rigorous iterations of action and reflection.
      The result was a clear definition of women-centred care, a set of general
      guidelines for practice, and specific changes to existing organizational
      policies. The process and the product of the research built a bridge between
      existing macro government policies and the guidelines, standards, and ethical
      codes of the professional health associations.

PMID- 11822563
TI  - Childbirth care-seeking behavior in Chiapas.
AB  - This study was designed to better understand how women in a developing region
      choose between the multiple options available to them for birthing. We conducted
      focused, open-ended ethnographic interviews with 38 nonindigenous, economically
      marginal women in Chiapas, Mexico. We found that although medical services for
      birthing were readily available to them, these women most often chose traditional
      birth attendants (TBAs) for assistance with their births. They expressed a clear
      preference for TBAs in the case of a normal birth, but viewed medical services as
      useful for diagnosing and managing problem deliveries and for tubal ligations.
      They favored TBAs because they valued being able to choose birthing locations and
      birthing positions and to have relatives present during the birth, all features
      they must give up for medically attended births in this region.

PMID- 11822564
TI  - A meta-analysis of fall prevention programs for the elderly: how effective are
      they?
AB  - BACKGROUND: Although fall prevention studies for the elderly have been reported,
      there is a paucity of work summarizing the effectiveness of these interventions.
      OBJECTIVES: The research question that guided this study was: 'What are the
      effects of fall prevention programs on the proportion of falls in the elderly?"
      METHOD: Meta-analysis was employed to summarize findings of intervention studies
      of fall prevention in the elderly involving a comparison group and a quantifiable
      outcome. Studies were reviewed by two of the authors with the eligibility
      criteria in mind. Studies were then coded and an inter-rater reliability check
      was performed. RESULTS: The overall mean weighted effect size for the 12 studies
      included in the meta-analysis was .0779 (Z = 5.03, p < .001). For fall prevention
      intervention types, exercise alone had a mean weighted effect size of .0220 (Z =
      .5303, p > .5), exercise and risk modification had a mean weighted effect size of
      .0687 (Z = 3.41, p < .001), and comprehensive risk assessment intervention
      studies had an effect size of .1231 (Z = 3.97, p < .001). The mean weighted
      effect size size for community-based studies was .0972 (Z = 5.37, p < .001) and
      for institution-based studies was .0237 (Z = .7822, p = .22). Time to outcome
      measure analyses revealed that the mean weighted effect size for studies
      measuring proportion of falls at 12 months was .0905 (Z = 5.43, p < .001), and
      those measuring at four months or less was -.0972 (Z = -.005, p > .50).
      CONCLUSIONS: The results of this meta-analysis indicate that there was a 4%
      decrease in the rate of falls for individuals who were in the treatment groups
      receiving various fall prevention interventions. Additional intervention studies
      need to be conducted in the elderly population with a goal of preventing falls.

PMID- 11822565
TI  - Lifestyle change in type 2 diabetes a process model.
AB  - BACKGROUND: Integration is an emerging concept in the study of self-management
      and chronic illness, yet this process and how it occurs is not well understood.
      OBJECTIVES: This investigation, part of a triangulated study, focused on the
      experience of integrating type 2 diabetes treatment recommendations into an
      existing lifestyle while participating in a nurse-coaching intervention. METHOD:
      An interpretive method elicited data from nurse-coaching sessions (4), field
      notes, and an interview in 9 women with type 2 diabetes. The process of data
      reduction and analysis (Miles & Huberman, 1994) was used to interpret data.
      RESULTS: The core process of integrating lifestyle change in type 2 diabetes was
      multifaceted and complex. Challenges to the process of integrating lifestyle
      change included reconciling emotions, composing a structure, striving for
      satisfaction, exploring self and conflicts, discovering balance, and developing a
      new cadence to life. These challenges required acknowledgment in order for
      participants to progress toward integration. DISCUSSION: Balance was an integral
      component to the experience of integration, between structure and flexibility,
      fear and hope, conflict and acceptance, diabetes and life. Conceptualizations
      identified with this investigation extend understanding of theories of
      integration and lifestyle change and invite the development and testing of
      nursing interventions.

PMID- 11822566
TI  - Acculturation, resilience, and depression in midlife women from the former Soviet
      Union.
AB  - BACKGROUND: A growing body of literature has demonstrated that demographic
      factors and acculturative stress contribute to depression in recent immigrants
      from many countries. Few studies examine potentially protective personality
      factors, such as resilience, for dealing with the challenges related to the early
      postmigration transition period. OBJECTIVES: The purpose of this analysis is to
      examine relationships among demographic characteristics, acculturation,
      psychological resilience, and symptoms of depression in midlife women from the
      former Soviet Union who recently immigrated to the United States. METHOD: Data
      for this analysis are from a larger cross-sectional study that explored the
      impact of immigration during midlife on women's health. The volunteer sample
      included 200 women from the former Soviet Union, 45-65 years old, who had lived
      in the U.S. fewer than 6 years. This analysis involves measures of acculturation,
      demands of immigration, resilience, and depressed mood. RESULTS: Findings include
      very high scores on the depression scale compared to U.S. norms. Older women, and
      those reporting greater demands of immigration, had higher scores on the
      depression scale. However, lower depression scores were found for women reporting
      greater English usage and resilience. DISCUSSION: The results corroborate
      previous studies that suggest high levels of depression in immigrant women, but
      additional validation is suggested to differentiate symptoms of depressed mood
      from clinical depression in this culture. Findings also suggest that
      interventions that encourage use of English language and enhance resilience may
      help decrease symptoms of depression in midlife women who are recent immigrants
      from the former Soviet Union.

PMID- 11822567
TI  - Factors influencing use of hearing protection among farmers: a test of the pender
      health promotion model.
AB  - BACKGROUND: Most farmers are exposed to potentially hazardous noise levels
      through many of their work activities, such as operating tractors, grain dryers,
      and chain saws. Rates of noise-induced hearing loss in this group are high.
      Although this condition is preventable through the use of hearing protection,
      rates of protective device use are low. Understanding factors influencing the use
      of hearing protection devices will provide direction for programs to increase
      their use and decrease risk of noise-induced hearing loss. OBJECTIVES: A study
      was designed using the Pender Health Promotion Model to identify factors
      affecting farmers' use of hearing protection devices. METHOD: Model testing was
      conducted with a convenience sample of 139 farmers. Prior to model testing,
      existing instruments designed to measure concepts from the Health Promotion Model
      were modified for use with farmers through interviews, validity testing with an
      expert panel, and reliability testing with first a small (n = 36) then a second
      larger (n = 139) convenience sample of farmers. Instruments measuring cognitive
      and affective factors related to hearing protection device use were administered
      to farmers at a regional farm show in the Midwest. RESULTS: A logistic regression
      analysis identified interpersonal support, barriers, and situational influences
      as statistically significant predictors of this health behavior, correctly
      predicting 78% of the cases. Results of model testing were consistent with
      results of previous studies of Health Promotion Model variables with other worker
      groups' use of hearing protection. CONCLUSIONS: Information from this study can
      be used to design and evaluate interventions to promote hearing protection device
      use among farmers and reduce the level of noise-induced hearing loss in this high
      risk and underserved worker group.

PMID- 11822569
TI  - The pin-striped habit balancing charity and business in Catholic hospitals, 1865
      1915.
AB  - BACKGROUND: Nursing literature seldom examines Catholic si. ters as entrepreneurs
      competing in the hospital marketplac even though they established hospitals
      throughout the United States in the late 19th and early 20th centuries.
      OBJECTIVES: This study examines the tension between hospita as businesses and
      charities by asking how nursing sisters, who took vows of poverty, could build
      impressive hospital networks. What links did they forge to make hospital building
      possible? METHOD: Historical methodology is used which draws upon primary sources
      in archives of three women's religious congregations. These include nuns'
      constitutions and letters, hospital chronicles, journals, minutes of meetings,
      annual reports and census records. Secondary sources include nursing hospital,
      religious, and economic histories. RESULTS: Catholic sisters' entrepreneurial
      activities were pragmatic adaptions that reflected their commitment to their
      nursing and hospital establishments. They raised money and formed alliances not
      to build personal fortunes but to build religious values. Their entrepreneurship
      and spirituality worked together. DISCUSSION: Sister-nurses' viewed their actions
      as doing what was necessary to their mission. A finacially stable hospital, with
      it's large patient population, enhanced the social and spiritual importance of
      nun's work. Yet, the broad-based corporate culture of Catholic hospitals still
      needs further study.

PMID- 11822570
TI  - Examining test-retest reliability: an intra-class correlation approach.
AB  - BACKGROUND: There are limitations of inter-class correlation (usually, the
      Pearson's product-moment correlation) in evaluating reliability of an instrument.
      An intra-class correlation approach would be appropriate to examine the test
      retest reliability of an instrument. OBJECTIVES: To introduce an intra-class
      correlation approach to examine the test-retest reliability of an instrument.
      METHOD: The method of constructing an intra-class correlation coefficient was
      presented. RESULTS: The instrument with visual analog scales to measure the
      perceived competence to practice breast self-examination and perceived barriers
      to breast self-examination was tested. The intra-class correlation coefficient
      was 0.640. CONCLUSION: The intra-class correlation is an alternative to test the
      reliability of an instrument and it is more sensitive to the detection of
      systematic error.

PMID- 11822568
TI  - Factors contributing to hospital readmission in a Hong Kong regional hospital: a
      case-controlled study.
AB  - BACKGROUND: As many as 50% of total hospital admissions are readmissions. Because
      the factors contributing to hospital readmission are multiple, and research
      findings are not conclusive, it is important for clinicians to gain an
      understanding of the key factors that contribute to readmission. OBJECTIVES: This
      study explores the factors contributing to hospital readmission and derives an
      explanatory model that can best identify characteristics of patients at high risk
      for hospital readmission. METHODS: This research was a case-controlled study with
      readmitted patients (n = 168) as the readmitted group and non-readmitted patients
      (n = 98) as the control group. The variables included demographic data, health
      assessment data, medical diagnosis, frequency of admissions, severity of illness,
      intensity of service and improvement of condition. The study sample was also
      interviewed to explore the patients' views on their repeated hospitalization.
      RESULTS: In the bivariate analysis significant differences between the study and
      control groups were multiple and generally consistent with findings in other
      studies. Using multiple logistic regression, however, the final model shows that
      only three factors best predict readmissions: frequency (3-4 times) of
      readmissions (OR = 9.96, p < .0001) and frequency (more than 5 times) of
      readmissions (OR = 15.73, p < .0001), financial assistance (OR = 5.03, p < .001),
      and severity of illness (OR = 3.12, p < .01). Our interview data suggest that the
      readmitted patients required assistance to accomplish daily living activities
      upon discharge and often returned to the hospital for the same health reason.
      CONCLUSION: The study findings suggest that patients who are frequently
      readmitted to the hospital are severely ill; are on public assistance; and may
      need special attention when discharged in order to attenuate repeated hospital
      readmission.

PMID- 11822571
TI  - Assessing group change under conditions of anonymity and overlapping samples.
AB  - BACKGROUND: A commonly used research design in the social sciences involves the
      matching of observations over 2 time periods (i.e., Time 1 --> Time 2) to assess
      group change. Because coupled observations are usually correlated, a paired- or
      dependent-samples t test is generally recommended in such applications to
      determine if there has been a statistically significant change in mean scores
      across time. Consequently, it is typically believed that unless information for
      matching respondents' observations is available, researchers have no choice but
      to treat the observations as if they were independent. OBJECTIVES: To demonstrate
      alternative statistical approaches for employing the paired samples ttest when
      information for matching respondents' observations is unavailable and to
      illustrate the applicability of these alternatives to longitudinal designs in
      which respondents at Time 1 are partially replaced by new respondents at Time 2.
      METHOD: Theoretical arguments and examples are employed to achieve the specified
      objectives. RESULTS/DISCUSSION: Performing an independent-samples ttest when a
      paired-samples t test is more appropriate will lead to a loss of statistical
      power and, thus, increase the likelihood of a Type II statistical error. The
      statistical approaches that are demonstrated allow researchers to account for
      pair wise dependency across observations and, therefore, to obtain a fairer test
      of group change in means.

PMID- 11822572
TI  - Sampling challenges in end-of-life research: case-finding for family informants.
AB  - BACKGROUND: Research on end-of-life care is hampered by challenges in accessing
      appropriate subjects for data collection. Although families of decedents are rich
      sources of research data, they are underutilized, most likely due to the access
      difficulties they present to investigators. OBJECTIVES: To describe case-finding
      strategies that can achieve a large and representative sample of family
      informants for research studies about end-of-life care. METHODS: Case-finding
      strategies were developed and honed over the course o fthree epidemiological
      studies on end-of-life care. Family location information was culled from death
      certificates and a combination of public and commercial sources. RESULTS: The
      researchers generated large random samples of study-eligible decedents and, using
      the case-finding strategies described, recruited family members of decedents as
      informants. By the third study, two-thirds of family members were located and
      interviewed within the narrow time frame of 2-5 months following the death of
      their loved one. DISCUSSION: Epidemiological studies on end-of-life, using large
      random samples of decedents and their family members, are feasible when armed
      with an array of effective case finding strategies.

PMID- 11822573
TI  - Carrying on: the experience of premature menopause in women with early stage
      breast cancer.
AB  - BACKGROUND: The survival benefit of adjuvant chemotherapy for breast cancer is
      established but the experience of organ system toxicity for women, specifically
      ovarian toxicity, is not fully known. OBJECTIVES: Th e purpose of the study was
      to develop asubstantive theory that would describe and explain women's responses
      to chemotherapy-induced premature menopause within the context of breast cancer.
      METHODS: Qualitative inquiry with Grounded Theory methodology was used to
      collect, code, and analyze the data. The purposive sample consisted of 27 women
      with early stage breast cancer who received adjuvant chemotherapy. The majority
      of women were married, well educated, and employed with a mean age of 41 years.
      Amenorrhea was reported by 24 women, a peri-menopausal pattern of bleeding was
      described by two women, and one woman had return of normal menses. Women
      participated in interviews ranging from 45 minutes to 2 hours and other data
      sources, such as informal discussions with oncology care providers, and lay
      women's writings about menopause and midlife women's health were used to increase
      interpretation of the data. RESULTS: Vulnerability was identified as the basic
      social psychological problem for women. Carrying On is the basic process that
      explains how women respond to vulnerability as they attempt to assimilate drug
      induced premature menopause into their breast cancer experience. The stages of
      Carrying On (Being Focused, Facing Uncertainty, Becoming Menopausal, and
      Balancing) progressed from minimizing the early menopause experience to
      developing an awareness to balancing the dynamic relationship of menopause and
      cancer in their lives. CONCLUSIONS: This study described the complexity of the
      experience of chemotherapy-induced premature menopause in women with early stage
      breast cancer and identified gaps in knowledge about menopausal symptom distress
      and factors influencing symptom management and outcomes in this population.
      Future research is needed to evaluate interventions during and after adjuvant
      therapy to improve the quality of survival of women who experience ovarian
      toxicity related to early stage breast cancer treatment.

PMID- 11822574
TI  - Gynecomastia in a patient with celiac disease.

PMID- 11822575
TI  - Congenital hypothyroidism with Prader-Willi syndrome.
AB  - We report a 1 year-old female patient with severe hypotonia who has congenital
      hypothyroidism and Prader-Willi syndrome (PWS). At birth she was found to have
      congenital hypothyroidism caused by an ectopic sublingual thyroid gland and was
      commenced on thyroid replacement therapy. She continued to have severe motor
      delay and therefore further diagnostic evaluation was performed. PWS was
      confirmed by DNA and fluorescence in situ hybridization (FISH) analysis. This
      report emphasizes the need to further investigate patients who are found to have
      congenital hypothyroidism and do not improve adequately on treatment.

PMID- 11822576
TI  - Educated?... For uncertainty.

PMID- 11822577
TI  - Type I collagen N-telopeptide variation in adolescents receiving oral
      isotretinoin for severe acne.
AB  - The prolonged use of retinoids has been reported to be associated with changes of
      bone biochemical markers and toxic skeletal effects. Among collagen markers, type
      I collagen N-telopeptide (NTx) is present in all tissues that contain type I
      collagen, mostly in bone and in cutaneous tissue. It is a reliable indicator of
      bone resorption in metabolic bone disease, but has not previously been
      investigated in dermatological diseases during retinoid therapy. Isotretinoin, a
      synthetic 13-cis-retinoic acid, is highly effective in the treatment of severe
      acne vulgaris. We evaluated the effect of low-dose short-term oral isotretinoin
      treatment on bone remodeling markers in 10 adolescents (mean age 17.8 years)
      affected by severe acne. We measured urinary NTx as a marker of bone resorption,
      alkaline phosphatase (ALP) and osteocalcin (OC) as markers of bone formation,
      parathyroid hormone (PTH) and metabolites of vitamin D (25OH-D3 and 1,25(OH)2D3).
      Clinical and laboratory tests were performed before and after three months of
      isotretinoin treatment at the dosage of 0.5 mg/kg/day. All patients showed a good
      clinical response to the treatment (7/10 marked improvement, 3/10 mild
      improvement). No changes were detected in serum PTH, 25OH-D3, 1,25(OH)2D3, OC and
      ALP, while urinary NTx concentrations were significantly reduced (p < 0.05). In
      conclusion, the lack of change in PTH, OC, ALP and vitamin D metabolites and the
      absence of increase of NTx suggest no bone effect of the isotretinoin treatment.
      The decrease of urinary NTx could be due to the effect of isotretinoin on the
      cutaneous component of type I collagen. Severe acne in the active inflammatory
      phase could change the levels of this marker. Thus, short-term low-dose oral
      isotretinoin is an effective and safe treatment for severe acne.

PMID- 11822578
TI  - Leptin, insulin-like growth factor (IGF)-I and IGF binding protein-3 levels in
      children with constitutional delay of growth.
AB  - This study was planned in order to investigate the role of insulin-like growth
      factor-I (IGF-I), IGF binding protein-3 (IGFBP-3) and leptin, the product of the
      ob gene synthesized by fat tissue cells, in constitutional delay of growth and
      puberty (CDGP) which is the most frequent cause of short stature in children.
      This study was conducted on 80 children with CDGP aged 6-15 years, and 60 healthy
      children served as controls. Serum IGF-I, IGFBP-3, insulin and plasma leptin
      levels were measured by immunoradiometric assay. Mean IGF-I and leptin levels
      were significantly lower in the CDGP group compared with the controls, but the
      mean IGFBP-3 level was not different in the two groups. Mean leptin levels were
      3.72 +/- 2.29 in CDGP and 4.68 +/- 3.08 in the control group (p <0.05). There was
      a statistically significant relationship between leptin levels and height,
      weight, and body mass index. Leptin levels were also correlated with
      chronological age, bone age and height age. When evaluated according to pubertal
      status, a significant difference was found in IGF-I, leptin and IGFBP-3 levels
      between prepubertal and pubertal groups. Leptin levels were significantly
      different in the prepubertal CDGP group compared with controls but in the
      pubertal CDGP group only IGF-I levels were significantly different from controls.
      As the weight of children with CDGP was lower than in the control group, it is
      postulated that the reason for short stature and pubertal delay may be this
      decrease in weight which is also the cause of low levels of leptin and IGF-I.

PMID- 11822579
TI  - Age-specific levels of diabetes-related GAD and IA-2 antibodies in healthy
      children and adults.
AB  - Glutamic acid decarboxylase (GAD) and tyrosine phosphatase IA-2 antibody levels
      were measured in 375 healthy children and adults and in 187 children with newly
      diagnosed type 1 diabetes mellitus (DM). GAD antibody levels were determined by
      radioimmunoassay, and IA-2 antibody levels by immunoprecipitation. Healthy
      children had higher GAD antibody levels than adults (p < 0.001). The 98th
      percentile was 1.60 U/ml in children and 1.16 U/ml in adults. IA-2 antibody
      levels did not differ between these two cohorts. Children with DM had higher GAD
      and IA-2 antibody levels than healthy children (p <0.001). Based on receiver
      operating characteristics (ROC) analysis, elevated levels of these antibodies
      showed high specificity rates (+/- SE) of 0.968 +/- 0.14 to 1.00 +/- 0.00. The
      sensitivity ranged between 0.439 +/- 0.037 (both antibodies elevated) and 0.850
      +/- 0.027 (at least one antibody elevated). These data emphasize the importance
      of establishing age-specific reference values for DM-related antibodies in the
      background population before applying them for screening and intervention
      studies.

PMID- 11822580
TI  - Effects of inhaled or nasal glucocorticosteroids on adrenal function and growth.
AB  - Inhaled and nasal glucocorticosteroids (GCS) have being shown to be very
      effective in the treatment of persistent asthma and allergic rhinitis. However,
      there has been great concern about the possible effects of these inhaled or
      nasally administered drugs upon the growth of patients of pediatric age. One of
      the possible glucocorticoid actions of GCS is reflected by the suppression of
      adrenal function, suggesting a peripheral direct effect of circulating GCS on the
      cartilage. The present review addresses the safety of inhaled and nasal GCS by
      assessing the literature on their effects on adrenal gland function and on growth
      in children and adolescents. It can be concluded that, at recommended doses,
      adrenal function is rarely suppressed. High doses of inhaled GCS seem to decrease
      short-term prepubertal growth, but available studies of final height show that it
      is not affected at licensed doses. Despite these observations, physicians should
      monitor the growth of their patients, particularly when a new drug is introduced.

PMID- 11822581
TI  - Incidence of childhood type 1 diabetes mellitus in Gomel, Belarus.
AB  - BACKGROUND: The importance of genetic and environmental factors in causing type 1
      diabetes mellitus (DM1) in many European countries is unknown. We studied this
      question by assessing the incidence of the disease in children in Gomel, Belarus,
      in the years subsequent to the Chernobyl disaster, comparing it to the antecedent
      period. METHODS: We identified all new patients with DM1 under 15 years at onset
      who presented between 1976 and 1999; we used as denominator the number of
      children aged 0-14 born in Gomel, to calculate the incidence. All data were
      validated by using the capture-recapture method. We compared the incidence rate
      between the periods before and after 1986; we also calculated the average
      increment of incidence in the latter period (1987-1999). RESULTS: In the whole
      period, 438 new patients presented, with an average crude rate of incidence of
      4.6/100,000 but with a net difference between the former (before 1986) and latter
      (after 1986) periods. The average standard incidence in the latter period was 5.7
      (C.I. 4.5-7.0), with a significant increase in the 10-14 year age group. The
      average yearly increase of incidence in the same period was 8.9%, highly
      significant (p < 0.001). CONCLUSIONS: The results seem to confirm the hypothesis
      of the influence of environmental pollution subsequent to the Chernobyl accident.

PMID- 11822582
TI  - Beta-cell response to intravenous glucagon in African-American and Hispanic
      children with type 2 diabetes mellitus.
AB  - The incidence of type 2 diabetes mellitus (DM) in children and adolescents has
      substantially increased over the past decade. The present study was conducted to
      evaluate the beta-cell response to intravenous glucagon (a non-glucose
      secretagogue) in children with type 2 DM. Twenty pediatric patients with type 2
      DM were compared to 15 control subjects matched for body mass index and sexual
      maturation. The patients' ages ranged between 10 and 19 years. The duration of DM
      ranged from 1 to 5 years. Nine patients were on insulin treatment and 11 were on
      diet alone (3 patients) or metformin (8 patients). The criteria for type 2 DM
      were absent islet cell (IA-2) and glutamic acid decarboxylase (GAD65) antibodies
      and a fasting serum C-peptide level of > or = 0.23 nmol/l. Plasma glucose and
      serum C-peptide levels were determined in the fasting state and six minutes after
      an intravenous injection of 1 mg of glucagon. The fasting and stimulated plasma
      glucose levels and the fasting serum C-peptide levels (1.02 +/- 0.43 vs 0.79 +/-
      0.26 nmol/l, p < 0.05) were higher in the patients with DM compared to weight
      matched control subjects. While the absolute C-peptide responses to glucagon were
      not different between the two groups, the stimulated C-peptide to glucose ratios
      were significantly lower in the patients with DM compared to controls (0.039 +/-
      0.026 vs 0.062 +/- 0.033, p < 0.05). Patients with DM treated with diet or oral
      therapy had significantly greater basal and stimulated C-peptide concentrations,
      incremental C-peptide, and C-peptide to glucose ratios than patients on insulin
      treatment. Both the fasting and the stimulated C-peptide levels were inversely
      correlated with the duration of DM (r = -0.53, p < 0.05). HbA1c at one year
      follow-up was inversely correlated with glucagon-stimulated C-peptide levels at
      the time of the study (r = -0.658, p < 0.01) and positively correlated with the
      duration of diabetes (r = 0.671, p = 0.002). The apparently normal serum C
      peptide levels measured after glucagon challenge in these children with type 2 DM
      reflect their higher glucose levels. The lower stimulated C-peptide to glucose
      ratios in these children with type 2 DM compared to normal controls demonstrate
      their diminished beta-cell response to intravenous glucagon, a non-glucose
      secretagogue. Among the patients with DM, a higher glucagon-stimulated serum C
      peptide response was associated with diet/metformin treatment, a shorter duration
      of DM and predicted improved glycemic control up to one year later. Thus, the
      fasting and glucagon-stimulated serum C-peptide levels provide an estimate of the
      potential insulin secretory capacity of the beta-cell and may predict glycemic
      control in pediatric type 2 DM.

PMID- 11822584
TI  - Rapid corticotropin versus corticotropin-releasing hormone test in girls with
      precocious pubarche.

PMID- 11822583
TI  - Lipoprotein (a) in obese children with a family history of cardiovascular
      disease.
AB  - OBJECTIVE: To analyze the influence of family history of cardiovascular disease
      (CVD) on lipoprotein (a) (Lpa) values in obese children. SUBJECTS AND METHODS:
      Lpa values were measured by a nephelometric technique in 837 prepubertal obese
      children (442 girls, 395 boys) aged 6-8 years. Lpa > 30 mg/dl were determined to
      be a risk factor for CVD after complete recording of dietary norms, family
      history of CVD and coronary risk in relatives aged less than 50 years old.
      RESULTS: The obese children's group with BMI > 30 and with family history of CVD
      presented higher values of Lpa (32.07 +/- 1.2 mg/dl) in comparison to the less
      obese group with family history of CVD (27.19 +/- 0.8 mg/dl) (p < 0.01), and both
      of these groups had significantly higher Lpa values than the groups with no
      family history of CVD. CONCLUSIONS: Childhood obesity with high BMI increases the
      risk of CVD when these children become adults in children with family risk
      factors for CVD.

PMID- 11822585
TI  - Psychogenic diabetes insipidus in toddlers with compulsive bottle-drinking: not a
      rare entity.
AB  - Psychogenic diabetes insipidus is commonly seen in adolescents but very rarely
      reported in toddlers. We report three toddlers who presented to our clinic with
      compulsive drinking behavior and polyuria. Laboratory work-up and water
      deprivation tests were consistent with psychogenic diabetes insipidus.

PMID- 11822586
TI  - Pseudotumor of the pituitary due to PROP-1 deletion.
AB  - Hypopituitarism associated with pituitary mass in childhood is most frequently
      the consequence of craniopharyngioma or Rathke's cleft cyst. We report a patient
      with an intrasellar pseudotumor associated with hypopituitarism, which led us to
      a misdiagnosis of intrasellar craniopharyngioma. After spontaneous involution of
      the mass, diagnosis was revised. DNA analysis showed a deletion in the Prophet of
      Pit-1 (PROP-1) gene, a pituitary transcription factor. It is important to
      recognize that a PROP-1 deletion can cause pituitary pseudotumor that can be
      mistaken for a craniopharyngioma or Rathke's pouch cyst.

PMID- 11822587
TI  - Spatiotemporal configuration dependent pairing of nerve events in dark-adapted
      human vision.
AB  - In the model presented here, in the dark any single quantum absorption in a rod
      or cone produces a subliminal excitation. Subliminal excitations from both halves
      of a twin unit pair in the retina for the perception of light from the stimulus.
      A twin unit contains either two red or two green cones. The twin units are
      intertwined in triples of two red units and one green unit in a hexagon called a
      trion. P satellite rods surround each cone, P being approximately proportional to
      the square of eccentricity. A successful pairing for light perception represents
      through the points of time and locations of the creation of its partners in the
      retina--a direction event with two possible polarities and with the orientation
      of the elongated shape of the twin unit. The polarity of the event depends on
      which of the two partners arrives first at the twin's pairing facility.
      Simultaneous events and successive events with the same polarity in adjacent
      units that are aligned along one of the three orientations of the hexagonal
      retinal mosaic pair in the cortex for the perception of edge and of movement.
      Inter-twin pairing products of the three differently oriented sets of aligned
      twins are independent of each other and sum vectorially in the cortex. This
      system of three sub-retinas is called the retrinet. Two one-quantum excitations
      in any of a twin's receptors make the percept colored. The odd blue cone produces
      already a blue signal for a single one-quantum excitation. Intra-receptor pairing
      in a rod, a red cone and a green cone is for white, red, and green respectively.
      Red and green cone products of a trion cross-pair in the retina and produce a
      yellow signal. Red and green cone products of a hexagon of adjacent trions cross
      pair in the cortex and produce a white signal. This large hexagon with a total of
      seven trions is called a persepton. After subliminal excitations in a twin have
      paired successfully, further subliminal receptor excitations in neighboring and
      aligned twins are expressed to a certain extent in the percept's area, duration
      and color. Earlier experiments on absolute and color thresholds are the basis for
      this theory, which is developed in this paper.

PMID- 11822588
TI  - De Vries-Weber gain control and dark adaptation in human vision.
AB  - Thresholds for seeing light from a stimulus are determined by a mechanism that
      pairs subliminal excitations from both halves of a twin unit. Such excitations
      stem from a package of k > or = 1 receptor responses. A half-unit contains one
      red or one green cone and P rods. The receptor's "Weber machine" controls the
      receptor's gain. Each half of a twin unit contains a "de Vries machine," which
      controls the half's k number. In the dark the receptor's dark noise events reset
      its Weber machine and the receptor's relation to its de Vries machine. A pairing
      product for light perception also represents a direction event. The local time
      signs of the two subliminal excitations are crucial for the polarity, size, and
      pace of the direction event. In relation to the time when and the area in which
      the stimulus is presented, these signs have average latency periods that depend
      on intensity and average locations that depend on movement. Polarity depends on
      which of the two subliminal excitations happens to arrive first at the twin's
      pairing facility. The intra- and inter-twin pairings in a persepton for the
      perceptions of light, edge and movement and the probability summation of the
      pairing products of the mutually independent three sets of twins of the retrinet
      improve intensity discrimination. Cross-pairings of intra-receptor pairings in
      red and green cones of a trion for yellow improve visual discrimination further.
      Discrimination of stimuli that exploit the model's entire summation mechanisms
      and pairing facilities represents "what the perfect human eye sees best." For the
      model this threshold of modulation in quantum absorption is the ideal limit that
      is prescribed by statistical physics. The lateral and meta interaction in a twin
      unit enhance the contrast of an edge and of a temporal transient. The precision
      of the local time sign of a half's stimulation determines the spatiotemporal
      hyperfunctions for location and speed. The model's design for the perfect retinal
      mosaic consists of red twins situated along clockwise and counterclockwise
      spirals and green twins along circles that are concentric with the fovea. The
      model's descriptions of discrimination, adaptation, and hyperfunctions agree with
      experimental data.

PMID- 11822589
TI  - Visual performance after correcting the monochromatic and chromatic aberrations
      of the eye.
AB  - The development of technology to measure and correct the eye's higher-order
      aberrations, i.e., those beyond defocus and astigmatism, raises the issue of how
      much visual benefit can be obtained by providing such correction. We demonstrate
      improvements in contrast sensitivity and visual acuity in white light and in
      monochromatic light when adaptive optics corrects the eye's higher-order
      monochromatic aberrations. In white light, the contrast sensitivity and visual
      acuity when most monochromatic aberrations are corrected with a deformable mirror
      are somewhat higher than when defocus and astigmatism alone are corrected.
      Moreover, viewing conditions in which monochromatic aberrations are corrected and
      chromatic aberrations are avoided provides an even larger improvement in contrast
      sensitivity and visual acuity. These results are in reasonable agreement with the
      theoretical improvement calculated from the eye's optical modulation transfer
      function.

PMID- 11822590
TI  - Spatial-frequency-tuned mechanisms of the red-green channel estimated by oblique
      masking.
AB  - The sustained spatial-frequency-tuned (SF-tuned) mechanisms of nonoriented units
      were examined by means of orthogonal masking for the Red-Green (R-G) color
      channel, and those of oriented units by oblique masking for the achromatic
      channel but not for the color channels. An oblique-masking technique minimizes
      the artifacts that are due to spatial phase effects, local cues, spatial beats,
      spatial probability summation, and changing criteria. Therefore the spatial
      characteristics of the R-G color channel are now investigated by an oblique
      masking technique and linked with my paper on orthogonal masking [J. Opt. Soc.
      Am. A 15, 1 (1998)]. The R-G channel was defined by the minimum-flicker and hue
      cancellation techniques. A color monitor system was used to generate spatially
      localized (D6) vertical color test patterns [0.063-8 cycles per degree (cpd)] and
      sinusoidal oblique color masks (0.031-16 cpd, 1.2-60% contrasts). Color contrast
      sensitivity functions (CSFs), threshold elevation (TE) versus mask SF (TvSF)
      curves, and TE versus mask contrast (TvC) curves were measured by the method of
      constant stimuli with a two-interval forced-choice technique by using Powell's
      achromatizing lens under sustained (Gaussian, 2-s-duration) conditions. Results
      show the following: (1) The color CSF is a low-pass function of SF with average
      half-height SF of 0.7 cpd and cutoff SF of 14 cpd with the use of a color
      detection criterion. (2) TvSF curves are broadly bandpass and fall into five
      groups, peaking at approximately 0.13, 0.5, 2, 4, and 8 cpd. The root-mean-square
      cone-color CSF is 3.8-5.4 times the stimulus-color CSF. (3) A "crowding effect"
      similar to that of the TvSF curves of the achromatic channel was also found, but
      the TvSF curves of the R-G channel are not sharply peaked, similar to the result
      for orthogonal masking. Data analysis led to the following conclusions: (1) A
      simple multiple-mechanism model yields one low-pass color mechanism (with average
      half-height SF of 0.54 cpd) and five bandpass SF-tuned color mechanisms; these
      six mechanisms are necessary to explain the CSF, TvSF, and TvC data
      simultaneously. (2) The bandpass mechanisms peaked at approximately 0.13, 0.5, 2,
      4, and 8 cpd with average full bandwidths at half-heights of 3.6, 3.2, 2.1, 1.2,
      and 1.3 octaves, respectively. (3) Since oblique-masking color mechanisms (unlike
      achromatic oriented mechanisms) have broad orientation tuning under sustained
      conditions and there is a significant orthogonal masking, the oblique-masking
      color mechanisms may have contributions from both oriented and nonoriented units.
      (4) The high degree of similarity between the SF-tuned filters of mechanisms
      derived from oblique- and orthogonal-masking data suggests that most of the
      chromatic SF tuning is already accomplished by nonoriented units. (5) The quality
      of the fit to oblique- and orthogonal-masking data combined dropped enough to
      reject the hypothesis that the former taps the performance of only the same
      nonoriented mechanisms as those by the latter. Adding gain parameters that reduce
      the TEs for orthogonal masking gave a better fit, suggesting that orientation
      gains are one of the factors involved in the transformation of information from
      nonoriented to oriented mechanisms. However, the fit was still worse than that
      for oblique-(6) Since masking-alone or orthogonal-masking-alone data, suggesting
      that more factors may be involved. primate parvo lateral geniculate nucleus
      (pLGN) units behave in a fairly linear manner, the color contrast nonlinearity
      (which follows the linear filter) of a mechanism may be post-pLGN.

PMID- 11822591
TI  - Relationship between subjective preference and alpha-wave activity in relation to
      temporal frequency and mean luminance of a flickering light.
AB  - Human cortical responses corresponding to the subjective preference for a
      flickering light under varying temporal frequency and mean luminance were
      investigated. Paired-comparison tests were performed to examine the subjective
      preference for a flickering light, and electroencephalograms (EEGs) were recorded
      from six electrodes (10-20 International Electrode Placement System) during
      presentations of the most-preferred and least-preferred flickering lights. The
      results showed a positive correlation between subjective preference and the
      effective duration of the autocorrelation function of the alpha waves measured at
      the visual cortex (O1 and O2 electrodes).

PMID- 11822592
TI  - Passive navigation from image sequences by use of a volumetric approach.
AB  - The paper describes a volumetric approach to depth estimation for robot
      navigation with use of only an approximately calibrated translating camera. Our
      approach is related to techniques for photo-realistic object reconstruction but
      with the emphasis on issues associated with navigation. The technique performs
      three-dimensional matching by a process of image interpolation and can adjust for
      errors in camera position. The reconstruction is achieved from a small angular
      range of scene views, and the technique is demonstrated to be insensitive to
      large errors in the camera positions. The ability to correct for more critical
      errors such as the camera orientation is shown to significantly improve the
      algorithm's performance. Our technique is demonstrated on real image sequences
      and compares favorably with techniques based on optical flow.

PMID- 11822593
TI  - Detection of objects composed of several regions by a region-configuration
      estimation method.
AB  - The task of detection of objects composed of several regions by means of
      statistical filters is analyzed. The target is assumed to have different unknown
      mean values in each of its regions. The detection is based on likelihood
      estimation, after performing an estimation of the actual configuration of the
      mean values in the target region. A simplified filter that reduces the
      computational complexity is also proposed. The statistical performance is
      analyzed theoretically and tested in computer experiments.

PMID- 11822594
TI  - Simulation of high-resolution x-ray zone plates.
AB  - A full-wave approach to quantitative characterization of x-ray zone plate lenses
      is proposed. Distributed focusing efficiency eta(z) of a multifocus optical
      element is defined as the energy flux through the Airy disk of a reference
      perfect lens with variable focal length z. Maxima of this function characterize
      diffraction efficiencies and spatial resolution of the zone plate foci. The
      parabolic wave equation is used to take into account diffraction effects inside
      the optical element. Rough and fuzzy interface models are introduced to describe
      realistic zone profiles. Numerical simulation reveals the limited capability of
      zone width reduction to improve the zone plate imaging performance. The
      possibilities of second-order focus enhancement by optimization of the zone plate
      thickness, line-to-space ratio, and zone tilt are studied numerically.

PMID- 11822595
TI  - Differential theory of gratings made of anisotropic materials.
AB  - Arbitrary profiled gratings made with anisotropic materials are discussed; the
      anisotropic character concerns electric and/or magnetic properties. Our aim is to
      avoid the use of the staircase approximation of the profile, whose convergence is
      questionable. A coupled first-order differential-equation set is derived by
      taking into account Li's remarks about Fourier factorization [J. Opt. Soc. Am. A
      13, 1870 (1996)], but the present formulation shows that, in return for a
      convenient form of the differential system, it is possible to use only the
      intuitive Laurent rule. Our method, when applied to the simpler case of isotropic
      gratings, is shown to be consistent with that of previous studies. Moreover, from
      the numerical point of view, the convergence of our formulation for an
      anisotropic grating is faster than that of the conventional differential method.

PMID- 11822596
TI  - Stable and efficient bloch-mode computational method for one-dimensional grating
      waveguides.
AB  - We present a stable and efficient method for the Bloch-mode computation of one
      dimensional grating waveguides. The approach uses the Fourier modal method and
      the S-matrix algorithm to remove numerical instabilities. The use of perfectly
      matched layers provide a high accuracy. Numerical results obtained for different
      lamellar grating waveguides and for both TE and TM polarizations illustrate the
      performance of the approach.

PMID- 11822597
TI  - Spectral changes and 1 X N spectral switches in the diffraction of partially
      coherent light by an aperture.
AB  - The off-axis and on-axis spectra in the far zone of an aperture for the case in
      which a particular class of partially coherent light with a broad spectrum is
      diffracted by an aperture are studied. It is shown that the spectrum in the far
      zone is generally different from that at the aperture; i.e., the spectrum is
      split into two or more peaks. Moreover, the spectrum varies with the diffractive
      angle. For a fixed diffractive angle, the spectral shift, defined as the
      difference between the frequencies at which the observed spectrum and the
      spectrum at the aperture take their maximum, shows a gradual change with the
      change in the coherence at the aperture. However, as the coherence reaches some
      critical values, the spectral shift exhibits a rapid transition; i.e., spectral
      switch occurs. The coherence that causes the spectral switch to take place is
      different for different diffractive angles. Therefore we propose a new kind of 1
      x N spectral switch, where N detectors (output ports) are placed at different
      diffractive angles in the far zone, and the spectral shifts at different
      detectors are measured. By adjusting the coherence of the aperture (input port)
      to the desired values, we obtain a rapid transition of the spectral shift in the
      desired output ports.

PMID- 11822598
TI  - Theory of singular-phase reconstruction for an optical speckle field in the
      turbulent atmosphere.
AB  - Analytical expressions are derived and computational algorithms are constructed
      for retrieving optical-field phase distribution under strong scintillation. The
      input data for the phase reconstruction are the wave-front slopes registered by a
      Hartmann sensor or shearing interferometer. The theory is based on representing
      the slope-vector field as the sum of its potential and solenoid components; it
      introduces the concept of phase-source and phase-vortex density and uses strict
      integral expressions relating these quantities to the wave-front slopes. To
      overcome the difficulties arising from the singular character of phase
      distribution, use is made of regularization of the wave-front slopes. The slopes
      can be measured with an ideal point wave-front sensor. It is shown that the
      slopes measured at the output of a nonideal sensor can be treated as regularized
      values of these slopes. Numerical simulation of phase unwrapping from the
      reference values of the wave-front slopes has shown that the algorithm designed
      for visualization of local phase singularities and those for phase reconstruction
      are very helpful in eliminating the measurement noise.

PMID- 11822599
TI  - Decoupled stochastic parallel gradient descent optimization for adaptive optics:
      integrated approach for wave-front sensor information fusion.
AB  - A new adaptive wave-front control technique and system architectures that offer
      fast adaptation convergence even for high-resolution adaptive optics is
      described. This technique is referred to as decoupled stochastic parallel
      gradient descent (D-SPGD). D-SPGD is based on stochastic parallel gradient
      descent optimization of performance metrics that depend on wave-front sensor
      data. The fast convergence rate is achieved through partial decoupling of the
      adaptive system's control channels by incorporating spatially distributed
      information from a wave-front sensor into the model-free optimization technique.
      D-SPGD wave-front phase control can be applied to a general class of adaptive
      optical systems. The efficiency of this approach is analyzed numerically by
      considering compensation of atmospheric-turbulence-induced phase distortions with
      use of both low-resolution (127 control channels) and high-resolution (256 x 256
      control channels) adaptive systems. Results demonstrate that phase distortion
      compensation can be achieved during only 10-20 iterations. The efficiency of
      adaptive wave-front correction with D-SPGD is practically independent of system
      resolution.

PMID- 11822600
TI  - Adaptive restoration of a partially coherent blurred image using an all-optical
      feedback interferometer with a liquid-crystal device.
AB  - A liquid-crystal adaptive optics system using all-optical feedback interferometry
      is applied to partially coherent imaging through a phase disturbance. A
      theoretical analysis based on the propagation of the cross-spectral density shows
      that the blurred image due to the phase disturbance can be restored, in
      principle, irrespective of the state of coherence of the light illuminating the
      object. Experimental verification of the theory has been performed for two cases
      when the object to be imaged is illuminated by spatially coherent light
      originating from a He-Ne laser and by spatially incoherent white light from a
      halogen lamp. We observed in both cases that images blurred by the phase
      disturbance were successfully restored, in agreement with the theory, immediately
      after the adaptive optics system was activated. The origin of the deviation of
      the experimental results from the theory, together with the effect of the
      feedback misalignment inherent in our optical arrangement, is also discussed.

PMID- 11822601
TI  - Hyperbolic representation of light propagation in a multilayer medium.
AB  - By analogy with the representation of the polarization of light on the Poincare
      sphere, we describe the propagation and the reflection/transmission of light in a
      multilayer on a hyperbolic surface. We show that the propagation of light
      corresponds to a classical rotation on this surface and that its
      reflection/transmission corresponds to a hyperbolic rotation.

PMID- 11822602
TI  - New layer-by-layer multilayer design method.
AB  - A new layer-by-layer multilayer design method is presented. The method is
      demonstrated mathematically and makes possible the optimization of the multilayer
      for the highest possible reflectance either at normal incidence or at nonnormal
      incidence for s- or p-polarized radiation. With the current method multilayers
      can be designed regardless of the number of different materials used. The optimum
      layer thickness is determined by means of functions suitable for implementation
      in a computer code. The new multilayer design method is fast and accurate.

PMID- 11822603
TI  - Reflectance enhancement in the extreme ultraviolet and soft x rays by means of
      multilayers with more than two materials.
AB  - Sub-quarterwave multilayer coatings with more than two different materials are
      shown to provide a reflectance enhancement compared with the standard two
      material multilayer coatings when reflectance is limited by material absorption.
      A remarkable reflectance enhancement is obtained when the materials in the
      multilayer are moderately absorbing. A simple rule based on the material optical
      constants is provided to select the most suitable materials for the multilayer
      and to arrange the materials in the correct sequence in order to obtain the
      highest possible reflectance. It is shown that sub-quarterwave multilayers
      generalize the concept of multilayers, of which the standard two-material
      multilayers are a particular case. Various examples illustrate the benefit of sub
      quarter-wave multilayer coatings for highest reflectance in the extreme
      ultraviolet. Applications for sub-quarterwave multilayer coatings are envisaged
      for astronomy in the extreme ultraviolet (EUV) and soft x rays and also for
      future EUY lithography.

PMID- 11822604
TI  - Near-field intensity distribution of waves scattered from slightly rough
      surfaces.
AB  - The near fields of electromagnetic waves scattered from two-dimensional slightly
      rough surfaces are studied by using the stochastic functional approach. The
      correlation coefficient between the surface and the intensity of the scattered
      wave field is investigated to estimate the fidelity of near-field intensity
      images. We show that the fidelity depends on both the polarization and the angle
      of incidence and that high fidelity can be obtained by a TM-polarized incident
      wave whose incident angle is not close to the critical angle of the total
      reflection.

PMID- 11822605
TI  - Analyses of vector Gaussian beam propagation and the validity of paraxial and
      spherical approximations.
AB  - The analysis of many systems in optical communications and metrology utilizing
      Gaussian beams, such as free-space propagation from single-mode fibers, point
      diffraction interferometers, and interference lithography, would benefit from an
      accurate analytical model of Gaussian beam propagation. We present a full vector
      analysis of Gaussian beam propagation by using the well-known method of the
      angular spectrum of plane waves. A Gaussian beam is assumed to traverse a charge
      free, homogeneous, isotropic, linear, and nonmagnetic dielectric medium. The
      angular spectrum representation, in its vector form, is applied to a problem with
      a Gaussian intensity boundary condition. After some mathematical manipulation,
      each nonzero propagating electric field component is expressed in terms of a
      power-series expansion. Previous analytical work derived a power series for the
      transverse field, where the first term (zero order) in the expansion corresponds
      to the usual scalar paraxial approximation. We confirm this result and derive a
      corresponding longitudinal power series. We show that the leading longitudinal
      term is comparable in magnitude with the first transverse term above the scalar
      paraxial term, thus indicating that a full vector theory is required when going
      beyond the scalar paraxial approximation. In spite of the advantages of a compact
      analytical formalism, enabling rapid and accurate modeling of Gaussian beam
      systems, this approach has a notable drawback. The higher-order terms diverge at
      locations that are sufficiently far from the initial boundary, yielding
      unphysical results. Hence any meaningful use of the expansion approach calls for
      a careful study of its range of applicability. By considering the transition of a
      Gaussian wave from the paraxial to the spherical regime, we are able to derive a
      simple expression for the range within which the series produce numerically
      satisfying answers.

PMID- 11822606
TI  - Magic, electromagnetism, and color: the language of transformation?

PMID- 11822607
TI  - Spirit of inquiry.

PMID- 11822608
TI  - Developing and evaluating CAM services.

PMID- 11822609
TI  - Physical exercise: the French military in World War I.

PMID- 11822610
TI  - Quantitative analysis of reproducible changes in high-voltage electrophotography.
AB  - OBJECTIVES: The existence of electromagnetic fields not generated by neuronal
      action or muscle stimulation remains controversial especially because they are
      difficulty to detect. We attempted to investigate the existence of
      electromagnetic fields associated with biologic systems using new image analysis
      techniques to analyze high-voltage electrophotography. DESIGN/SUBJECTS: Five
      energy practitioners (three males and two females) and five control subjects
      (four males and one female) participated in the study. Each practitioner had
      studied a formal training curriculum and was a professional energy practitioner.
      Images representing attempts of both energy practitioners and controls to elicit
      a change in electromagnetic emissions were captured by electrophotographic means.
      A statistical analysis on the comparison of "ON" vs. "OFF" states for the
      controls and practitioners in the study was made via digital representation of
      analogue images. RESULTS: Our interest was threefold: (1) to determine whether
      corona discharge patterns could be obtained and photographed and be reproducible;
      (2) to quantify some of the qualitative properties of the coronas; and (3) to
      determine if individuals can alter, at will, their electrophotographic images. We
      found a correlation between a change in the electromagnetic emissions for the
      body and the conscious desire of an energy practitioner to change this state.
      Analyses of individual finger coronas demonstrate statistically significant
      differences as analyzed by overall color changes and via analysis of individual
      sections of the various colors dominating the field. Control subjects were unable
      to produce statistically significant changes that were reproducible. Physiologic
      processes, such as changes in skin resistance, sweating, and surface blood
      constriction, have been suggested as an explanation of the colors and patterns
      that appear on the film in previous studies, but were not observed in this
      investigation. CONCLUSIONS: After controlling for the above variables and
      identifying reproducible and statistically significant changes, we believe the
      images created in our study represent the interaction of biologically generated
      electromagnetic fields interacting with the corona discharge created by the
      electrophotographic device.

PMID- 11822611
TI  - A pilot project to assess the methodological issues involved in evaluating
      acupuncture as a treatment for disabling breathlessness.
AB  - OBJECTIVES: This pilot study explores the methodological implications of
      evaluating the use of acupuncture in the treatment of disabling breathlessness.
      DESIGN: A randomized, controlled trial involving three treatments that were used
      on one occasion, each in random order. SETTINGS: The study was designed to
      evaluate the feasibility of providing acupuncture treatment on a domiciliary
      basis, in Southampton (United Kingdom) to patients with disabling breathlessness.
      SUBJECTS: Sixteen (16) subjects with disabling breathlessness caused by chronic
      lung disease (primarily chronic obstructive pulmonary disease [COPD]) were
      recruited from the respiratory medicine clinics of Southampton University
      Hospitals Trust. INTERVENTIONS: The treatments were real acupuncture, dummy
      acupuncture, and mock transelectrical nerve stimulation (TENS). OUTCOMES: To
      evaluate the respiratory outcome measures, to look at the credibility of the
      three treatments (using a previously validated Borkovec and Nau scale), and to
      calculate the sample size for a larger, more definitive study. RESULTS: Twelve
      (12) subjects completed the study. The acupuncture was a predefined point
      prescription that had been found previously to be of value in this condition, an
      approach that could be taught to health professionals and provided on a
      domiciliary basis. The treatment was provided only on one occasion, therefore, we
      did not expect a clear therapeutic benefit to emerge, but some nonsignificant
      benefit was noted as a consequence of acupuncture treatment. The shuttle test
      that we used as an objective measure of breathlessness was impractical in a
      domiciliary environment and will not be used in further studies. Each of the
      three treatments was equally credible at the outset, although real and dummy
      acupuncture were considered by the patients to be preferable choices after the
      completion of treatment. CONCLUSIONS: It was possible to carry out this study on
      a domiciliary basis. The information obtained will allow us to design a much
      clearer definitive study and the small, but statistically insignificant, response
      to acupuncture has allowed us to estimate sample size.

PMID- 11822612
TI  - The diagnosis and treatment of patients with chronic low-back pain by traditional
      Chinese medical acupuncturists.
AB  - The selection of appropriate treatments in clinical trials of acupuncture
      requires understanding how acupuncturists diagnose and treat specific conditions.
      We examined the Traditional Chinese Medical (TCM) diagnoses and treatments for
      patients with chronic low-back pain using two separate sets of treatment records.
      Information from more than 150 initial visits was available for analysis. A
      diagnosis of Qi and Blood Stagnation or Qi Stagnation was made for 85% of
      patients. A diagnosis of kidney deficiency (or one of its three subtypes) was
      made for 33%-51% of patients. Other specific diagnoses were made for less than
      20% of the patients. An average of 12-13 needles was used in each treatment.
      Although more than 85 different acupoints were used in each data set, only 5 or 6
      acupoints were used in more than 20 of the treatments in each data set. Only two
      of those acupoints (UB23, UB40) were the same for both sources of data. More than
      half of the patients received adjunctive treatments, including heat (36%-67%),
      and cupping (16%-21%). There was substantial variability in treatments among
      providers. Such diversity will make it challenging to select a single treatment
      that has wide applicability. We recommend that researchers attempt to develop a
      treatment that is considered credible by expert acupuncturists and has broad
      features characteristic of patterns of common clinical practice.

PMID- 11822613
TI  - An exploratory pilot study of acupuncture on the quality of life and reproductive
      hormone secretion in menopausal women.
AB  - The majority of menopausal women suffer from climacteric symptoms. The purpose of
      this study was to assess the effects of acupuncture on the quality of life and
      reproductive hormones secretion in menopausal women. Eleven (11) menopausal women
      with climacteric symptoms entered this prospective study. The Menopause Specific
      Quality of life Questionnaire was filled out by the patients before the first
      acupuncture session, after the last one (5 weeks later), and 3 months after the
      last acupuncture session. Reproductive hormones including follicular-stimulating
      hormone (FSH), luteinizing hormone (LH), estradiol, progesterone, and prolactin
      were measured before and after treatment. Acupuncture significantly improved
      menopausal vasomotor symptoms (p = 0.001 and p = 0.003 for the end of treatment
      and 3 months later, respectively) and physical symptoms (p = 0.014 at the end of
      treatment and p = 0.046 3 months later). It did not change psychosocial or sexual
      symptoms, nor did it change the measured reproductive hormones. In conclusion,
      acupuncture is shown to be effective in relieving vasomotor and physical
      disturbances of menopausal women with effects lasting at least up to 3 months
      after termination of the treatment. Acupuncture may be a useful treatment
      alternative for women who are unable or do not want to receive hormone
      replacement therapy. A prospective study with larger sample sizes will be needed
      to define the role of acupuncture in the management of menopausal symptoms.

PMID- 11822614
TI  - Use of complementary and alternative medicine among women in New York City: a
      pilot study.
AB  - OBJECTIVE: This study documents the use of complementary and alternative medicine
      (CAM), among White, African American, and Hispanic/Latina women living in New
      York City. A pilot to a national survey of CAM use among American women, this
      study explores women's use of categories of CAM and various CAM practitioners,
      racial and ethnic differences in CAM use, and women's perceptions regarding the
      effectiveness of CAM. DESIGN AND LOCATION: Data were collected from women
      residing in New York City using random digit dialing/computer-assisted telephone
      interviewing (CATI). The sample of 300 had equal numbers of women (n = 100) who
      self-identified as White, Hispanic/Latina, and African American, equally
      stratified by age (below and above age 40). SUBJECTS: Eligibility requirements
      included self-identification as Anglo/white, African American, or Hispanic/Latina
      and between ages 18 and 80. MEASURES: Three distinct categories of CAM were
      explored: (1) medicinal teas, homeopathic remedies, herbs, vitamins; (2) yoga,
      meditation, spiritual practices; and (3) manual therapies including chiropractic,
      massage, acupressure. Health concerns of interest were those frequently described
      in prior focus groups, and included reproductive health issues (e.g., pregnancy,
      menstruation, menopause) as well as other common women's health problems (e.g.,
      heart disease, high blood pressure, headaches). RESULTS: More than half the
      sample has used a CAM treatment or remedy, and 40% have visited a CAM
      practitioner. Among users, half have used only one of the CAM categories,
      approximately one third have used two, and 16% used all three. The category of
      CAM used most often was medicinal tea/herbs/vitamins; the practitioners visited
      most frequently were chiropractors (18%) and nutritionists (17%). Racial and
      ethnic differences in CAM use were minimal, and approximately one third of all
      treatments used were rated "very effective" by users. CONCLUSIONS: Substantial
      utilization of CAM remedies and treatments for a variety of women's health
      concerns is observed. Further inquiry with larger samples of women is
      recommended.

PMID- 11822615
TI  - Dietary supplement survey of pharmacists: personal and professional practices.
AB  - OBJECTIVE: To survey pharmacists about personal/professional practices regarding
      dietary supplements, specifically personal use and recommendation patterns,
      reference usage, and desired computerized decision-support features. DESIGN:
      Anonymous, self-administered survey. SETTING/LOCATION: National pharmacy
      association meeting. SUBJECTS: Practicing pharmacists who answered questions
      about dietary supplements. OUTCOME MEASURES: Acceptability of specific
      references, desired features in computerized decision support, frequency of
      personal use, and recommendations to patients, family, or friends. RESULTS:
      Seventy (70) pharmacists completed the survey. A majority (52.9%) reported taking
      dietary supplements including echinacea, zinc, and chromium picolinate. Fewer
      than half of pharmacists stated they have recommended a dietary supplement to a
      patient. Pharmacists stated that the top information sources were: published
      clinical trials, allopathic health care providers, alternative medicine
      practitioners, and word of mouth. The Internet was an important source for
      recommendations although not for personal use. The most highly accepted (>70%)
      print references included The Review of Natural Products and the World Health
      Organization Monographs on Selected Herbal Products. More than 90% rates the
      ability to view reference citations and computerized alerts on drug-dietary
      supplement interactions "very important" or "important". Interest was high in
      accessing computerized monographs. CONCLUSIONS: Pharmacists are self-educating
      about dietary supplements. Among pharmacists surveyed, there was some consensus
      as to which references were acceptable. There is a demand for dietary supplements
      information to be included in pharmacy computer systems, specifically to check
      for interactions against the patient's.drug profile. Although practitioners in
      Western and alternative medicine, as well as journal articles, are preferred
      information sources, the Internet and word of mouth are also important sources.
      Personal use of dietary supplements correlated with a twofold increase in the
      likelihood that a pharmacist would recommend a dietary supplement to a patient.

PMID- 11822616
TI  - Attitudes toward integration of complementary and alternative medicine with
      hospital-based care.
AB  - OBJECTIVE: To characterize those who have used, expect to use, or are opposed to
      the use of holistic therapies, especially in a conventional medical (hospital)
      setting. SAMPLE DESCRIPTION AND METHODS: Cross-sectional survey of a random
      sample of Hamilton-Wentworth residents between March and June 1998 (n = 416;
      response rate, 63%); analysis used logistic regression. RESULTS: Thirty-seven
      percent (37%) used at least one holistic therapy in the previous year: the three
      most common were chiropractic, massage, and herbal/phytology. The three most
      common reasons for use were general health, fatigue, and arthritis. Thirty-three
      percent (33%) would use holistic therapy in the future. Barriers to use were lack
      of information, perceived ineffectiveness, and cost; approximately 40% agreed
      they would only use holistic therapies with medical advice. Approximately 13%
      were opposed to holistic therapy and objected to its use in hospitals. Younger
      age, preference for holistic therapy over conventional medicine, and prior use of
      holism independently predicted high likelihood for future use. Lower income and
      high self-perceived health were associated with negative attitude toward use of
      holistic therapies in hospital. CONCLUSION: Most respondents would accept
      integration of holistic techniques into a hospital; therapies would be more
      acceptable if there were clear evidence of their efficacy. A few might find their
      opinion of a sponsoring hospital lowered by such integration.

PMID- 11822617
TI  - Barriers to acceptance: an exploratory study of complementary/alternative
      medicine disuse.
AB  - BACKGROUND: Previous research indicates wide use of complementary and alternative
      medicine (CAM). While understanding this trend is certainly important, an equally
      meaningful although largely unexamined research question is: why do the majority
      of patients and individuals fail to avail themselves of such therapies?
      Understanding these factors may be particularly important given the increasing
      evidence suggesting that certain of these therapies may be efficacious. METHODS:
      A two-page survey that examined demographic characteristics, attitudes toward
      CAM, and rates of use of specific CAM therapies was mailed to a randomly selected
      sample of 1680 Stanford University alumni. A total of 601 responses were received
      (response rate, 35.8%). Multiple regression analyses were carried out to examine
      predictors of general CAM disuse and disuse of specific therapies. RESULTS: The
      following variables predicted disuse of CAM in general (p < 0.05): (1) being male
      (odds ratio [OR] 0.65; 95% confidence interval [CI] 0.44-0.98); (2) being healthy
      (OR 0.95; 95% CI 0.91-0.99); (3) lack of physician support for CAM use (OR 1.82;
      95% CI 1.42-2.29); and (4) believing CAM treatments are ineffective or inferior
      (OR 0.27; 95% CI 0.19-0.38). Lack of knowledge about CAM approached significance
      (p = 0.068). With regards to specific therapies, the following patterns were
      seen: disuse of massage was associated with being male and younger; lack of
      physician support predicted disuse for all treatments except acupuncture and
      homeopathy; the belief that CAM treatments in general are ineffective predicted
      disuse of all therapies except chiropractic while the belief that chiropractic
      was ineffective predicted its disuse; the perception that CAM produced negative
      side-effects predicted disuse of chiropractic; lack of knowledge of CAM predicted
      disuse of herbs, chiropractic, and homeopathy; positive health status was
      associated with disuse of chiropractic; and finally, the perception that
      providers were not in accessible locations predicted disuse of all CAM therapies
      except homeopathy and meditation. CONCLUSIONS: Study findings indicate people are
      less likely to use CAM if they are male, are in good health, believe that the
      therapies are in general ineffective or inferior to conventional methods,
      perceive that conventional medical doctors are not supportive, and to a lesser
      extent feel they do not have adequate knowledge of CAM. Specifically, avoidance
      of chiropractic is associated with concerns for safety and side-effects. For
      treatments that are more provider-based as opposed to self-care based, lack of
      accessibility-to providers may explain disuse. As researchers continue to
      demonstrate the clinical efficacy of CAM therapies, these preliminary findings
      deserve attention because they highlight potential reasons why patients and
      physicians may be biased against or unable to avail themselves of such therapies.

PMID- 11822618
TI  - Ethical issues regarding fee-for-service-funded research within a complementary
      medicine context.
AB  - Ethical issues are presented concerning the appropriate use of a fee-for-service
      strategy to fund clinical research assessing preventive complementary medicine
      approaches, particularly the effectiveness of dietary supplements for disease
      prevention. Reasons for the need for such an alternative funding approach are
      identified and historical precedents are noted. Presuming a priori key desiderata
      of doing no harm, not taking advantage of the ill, and pursuing recognized useful
      purposes, six key ethical questions from the relevant literature are identified
      and discussed. Arguments are advanced that there is a sound rational, ethical
      basis (1) to ask patients to pay for clinical experimentation in the focused area
      of supplement-directed disease prevention; (2) to accept the reality that those
      who cannot pay may not participate; (3) to permit moderate profit from the
      ongoing research; (4) to allow researchers to receive fees for their support of
      such clinical research; (5) to pursue this alternative funding strategy in
      addition to conventional sources; and (6) to expect that patients can give
      informed consent in such settings. It is demonstrated that patient-funded
      research has been an integral component of clinical research for decades and that
      there is no inherent reason why explicit patient payment of fees need be less
      ethical than any other commonly accepted funding models. Accordingly, an ethical
      case is made for the appropriateness and value of significantly expanded fee-for
      service-funded research within a complementary medicine context, particularly the
      assessment of dietary supplements for disease prevention.

PMID- 11822619
TI  - Interim progress report: White House Commission on Complementary and Alternative
      Medicine Policy.

PMID- 11822620
TI  - Surveys of complementary and alternative medicine: part IV. Use of alternative
      and complementary therapies for rheumatologic and other diseases.
AB  - This fourth review in the series covers eight recent U.S. surveys on
      complementary and alternative medicine (CAM) use by patients with rheumatologic
      and other autoimmune conditions, and summarizes seven studies of other disease
      categories. Regarding the previous reviews, the acronym CAM is used unless it is
      possible to refine the concepts. This reflects the problem that most survey
      questionnaires do not differentiate between adjunct or complementary therapies
      and alternative approaches to treatment.

PMID- 11822621
TI  - A comprehensive information resource on traditional, complementary, and
      alternative medicine: toward an international collaboration.
AB  - OBJECTIVES: A prototype for a comprehensive information resource for traditional
      complementary and alternative medicine (TCAM) has been developed to fill the
      considerable needs of a broad audience for worldwide access to TCAM information.
      The proposed resource is to be a comprehensive, vocabulary-controlled,
      integrated, standardized, multimedia information resource for TCAM. It will
      facilitate international cooperation, promote synergistic development of
      individual resources, promote dissemination of TCAM knowledge, and map the
      interrelationships among the TCAM traditions. METHODS: We organized two workshops
      for representatives of international databases that contain significant
      information on various aspects of alternative medicine. For the first workshop,
      we prepared and demonstrated a prototype named Complementary and Alternative
      Medicine Digital Library (CAMed) to illustrate the anticipated structure,
      content, and functionality of the comprehensive resource. We then constructed a
      second prototype to demonstrate the possibilities of searching across the
      collaborating databases and presented it to the representatives at the second
      workshop. OUTCOMES: Representatives of nine international databases attended the
      two workshops, in Bangalore, India (1998), and in Seoul, Korea (1999). We
      presented the prototypes at the workshops. Prototype I uses a Web interface, and
      supports browsing and searching from a variety of access points. Prototype II
      demonstrates a functional system that provides simultaneous access to selected
      represented databases by searching thesauri of these databases through our
      system. The group formalized itself as the International Collaboration for
      Information on Complementary and Traditional Medicine (IC2TM) with a goal of
      fully realizing the potential of the project.

PMID- 11822622
TI  - East meets West: facing common issues of integrating traditional and Western
      medicine.

PMID- 11822623
TI  - The puzzle of homeopathy.
AB  - Homeopathy is a branch of Western medicine that has mostly been rejected by
      Western orthodoxy for the last 200 years because of conceptual and scientific
      clashes. Homeopathy uses microdoses of potential toxins to provoke defense and
      self-regulatory responses, rather than the more orthodox approach of blocking
      body reactions. This approach hints at its clinical scope: it can help, at times
      resolve, conditions that are intrinsically reversible rather than mechanical
      problems, deficiencies, or irreversible breakdowns in body functions where it is
      only palliative. In recent years, there has been a renaissance of interest.
      Public demand has soared, and with it professional interest. Approximately 20% of
      Scotland's general practitioners have completed basic training. This is partly
      occasioned by public interest in complementary medicine and a sympathy with the
      more mind-body approach of homeopathy, and partly by recent scientific evidence.
      Some homeopathic dilutions are so extreme they are dismissed by critics as only
      placebo. Yet trials and meta-analyses of controlled trials are pointing toward
      real effects, mechanism of action unknown. Clinical outcome studies suggest
      useful clinical impact and excellent safety. There seems to be a potential to
      enhance patient care by integrating the two systems.

PMID- 11822624
TI  - Historical and professional perspectives of complementary and alternative
      medicine with a particular emphasis on rediscovering and embracing complementary
      and alternative medicine in contemporary Western society.
AB  - Harvard University, the oldest university in the United States, established its
      medical school in 1782. Harvard Medical School led the way in reform of medical
      education and in medical research. Since the school's earliest days, Harvard
      physicians and scientists have demonstrated that treatments are often found
      beyond the boundaries of prevailing medical practice. In 1802, Professor Benjamin
      Waterhouse, having learned of Edward Jenner's pioneering work, introduced the
      smallpox vaccine to America. Later in the nineteenth century, Dr. Oliver Wendell
      Holmes promoted new standards of sanitary practice, despite the skepticism of
      many fellow physicians. In 1847, Dr. John Collins Warren first publicly
      demonstrated the use of clinical anesthesia with ether. This tradition of inquiry
      and innovation has continued into the present century, as attested by the 15
      Nobel prizes awarded to Harvard Medical School scientists. It is in this spirit
      of open-minded inquiry and rigorous scientific standards that Harvard Medical
      School now looks into complementary and alternative medicine. The popularity of
      complementary and alternative treatments has grown enormously in recent years.
      Physicians must understand what therapies our patients are using and how these
      therapies work. We must ask if these therapies interact with medicines we
      prescribe. We must recognize that medical care is both science, and a connection
      between patient and healer. And we must be open to the likelihood that, as in the
      past, some therapies that are now considered alternative will be standard
      practice in the future.

PMID- 11822625
TI  - Clinical applications of acupuncture: an overview of the evidence.
AB  - This presentation provides an overview of studies that are of sound
      methodological quality and that contribute to the understanding of acupuncture.
      It is difficult to design an appropriate control group for acupuncture because
      acupuncture is an invasive, physical modality. No single control group can answer
      all of the research questions. Therefore, many types of control groups, each with
      advantages and disadvantages, have been used, depending on the specific questions
      being asked. Examples are taken from the different categories of control groups
      (e.g., acupuncture versus standard medical care). A model for future acupuncture
      research, which is simultaneously comprehensive and cost effective, is described.

PMID- 11822626
TI  - A brief commentary: electroacupuncture may relax the contraction of sphincter of
      Oddi.
AB  - Animal studies have shown that acupuncture can affect the function of the
      sphincter of Oddi, a smooth muscle encircling major papilla located at the second
      portion of the duodenum that regulates the flow of bile and pancreatic juice.
      This study of thirteen patients was the first to observe the effects of
      acupuncture on sphincter of Oddi motility in humans. Stimulation of the
      acupuncture point GB-34, which is known to Oriental medicine as an acupoint with
      effect on the biliary system, showed reversible inhibition of sphincter of Oddi
      contractions. In contrast, stimulation of a nonspecific control acupoint did not
      induce significant change. This study suggests that acupuncture may be one
      alternative treatment for patients with sphincter of Oddi dysfunction.

PMID- 11822627
TI  - Research on the neurophysiological mechanisms of acupuncture: review of selected
      studies and methodological issues.
AB  - This presentation reviews studies that contribute to an understanding of the
      neurophysiological mechanisms of acupuncture. A 1973 study, using volunteer
      medical students, looked into acupuncture's analgesic effect on experimentally
      induced pain and suggests that humoral factors may mediate acupuncture-induced
      analgesia. In a study of the possible role of the cerebrospinal fluid
      transmission of pain suppression effects of acupuncture, cerebrospinal fluid from
      acupuncture-treated rabbits was infused into recipient rabbits. The analgesic
      effect was observed in the recipient rabbits, suggesting that acupuncture-induced
      analgesia may be mediated by substances released in the cerebrospinal fluid.
      Studies of electroacupuncture in rats revealed that both low-frequency and high
      frequency stimulation could induce analgesia, but that there are differential
      effects of low- and high-frequency acupuncture on the types of endorphins
      released. In another study, low-frequency electroacupuncture, given as median
      nerve stimulation in cats, was shown to protect the myocardium by inhibiting
      sympathetic pressor response and increasing myocardial oxygen demand. The
      development of neuroimaging tools, such as positron emission tomography (PET) and
      functional magnetic resonance imaging (fMRI), make noninvasive studies of
      acupuncture's effects on human brain activity possible. Studies using PET have
      shown that thalamic asymmetry present among patients suffering from chronic pain
      was reduced after the patients underwent acupuncture treatment. Other studies,
      using fMRI, have pointed to relationships between particular acupoints and visual
      cortex activation. These powerful new tools open the possibility to new
      scientific studies of this ancient therapy.

PMID- 11822628
TI  - Seminal studies in acupuncture research.
AB  - Acupuncture, a component of the health care system of China that can be traced
      back at least 2500 years, describes a family of procedures involving stimulation
      of anatomical locations on the skin by a variety of techniques. In November 1997,
      the National Institutes of Health conducted a consensus conference during which a
      panel of experts convened to discuss the scientific evidence regarding
      acupuncture. The panel concluded that acupuncture is an effective treatment for
      several medical conditions and described biochemical and physiologic mechanisms
      that begin to explain these effects. This presentation summarizes the evidence of
      the clinical efficacy of acupuncture and is divided into three segments. The
      first segment presents an overview of evidence-based medicine, the second segment
      summarizes the current evidence from systematic reviews of acupuncture, and the
      third segment looks to the future by proposing a stepwise method for designing
      phase I, II, and III acupuncture clinical trials.

PMID- 11822629
TI  - Publication of complementary and alternative medicine research in mainstream
      biomedical journals.
AB  - The growing interest in complementary and alternative medicine (CAM) among the
      public, patients, physicians, and academic medical centers has been accompanied
      by an increasing amount of research and publication of articles on unconventional
      medicine in mainstream biomedical journals. This presentation highlights recent
      trends in the publication of research articles on CAM therapies in major medical
      journals; delineates issues related to journal policies, scientific evaluation,
      and editorial decision-making regarding submitted manuscripts; and discusses the
      role of leading medical journals in providing reliable, evidence-based
      information on complementary and alternative medicine to the medical community
      and the public.

PMID- 11822630
TI  - A critique on complementary and alternative medicine.
AB  - Modern medicine regularly uses the products of science to improve health. Until
      recently, however, medicine itself has not been practiced in a scientific manner.
      The growth of evidence-based medicine is predicated upon the concept that insofar
      as possible, all aspects of medical care ought to be examined with regard to the
      evidence. All forms of treatments and preventive strategies should be subjected
      to assessments of efficacy and effectiveness. Efficacy is demonstrated in the day
      to-day practice of medicine. An evaluation of effectiveness may lead to one or
      more randomized clinical trials, where the results of these randomized clinical
      trials may be necessary to maximize effectiveness. From a health care
      perspective, safety must be assessed, not only with regard to adverse effects of
      the particular intervention, but also in the context of a comparison to
      alternative treatments. If evidence demonstrates the efficacy and/or
      effectiveness of a particular intervention, it may be unsafe to select a
      treatment for which evidence of efficacy or effectiveness is lacking. Certainly
      patients should be fully informed of the evidence that is available for making
      rational choices. Alternative and complementary modes of medicine should be
      subject to these principles. The history of digitalis glycosides provides an
      interesting example of an important treatment arising from herbal medicine, by
      which many of these elements can be exemplified.

PMID- 11822631
TI  - Report by David M. Eisenberg, M.D., on complementary and alternative medicine in
      the United States: overview and patterns of use.
AB  - In the first of his two presentations, David Eisenberg, M.D., discussed four
      topics. First he reviewed current complementary and alternative medicine (CAM)
      terminology and definitions. Then, based on two studies he conducted in 1990 and
      1997, he summarized patterns of complementary medicine use in the United States.
      Next, he raised the implications of his findings on research and policy-making.
      And, finally, he highlighted opportunities to develop a collaborative
      international agenda.

PMID- 11822632
TI  - Comments on complementary and alternative medicine in Europe.
AB  - Despite the advances in Western medicine, up to one in three people in
      populations served by this medical system are seeking some form of unorthodox
      care each year, and Europe is no exception. Patients have driven this change, to
      the point where complementary and alternative medicine (CAM) is the second
      biggest growth industry in Europe. Often patients have to rely on the growing
      numbers of CAM practitioners with a variable standard of care that ranges from
      excellent to dangerous. Many practitioners work without regulation or even work
      illegally. Many orthodox health care professionals have shared their patients'
      concerns. Over the last 15 years, these practitioners have moved from silent
      interest to open enquiry and growing use. For example, approximately one in five
      of Scotland's general practitioners have received basic training in integrating
      homeopathy with orthodox practice. The demand for CAM is in part a search for a
      broader range of therapies, but is also a call for a different approach to care,
      with less emphasis on drugs, and a more whole-person approach. Mostly, people
      look to CAM when orthodoxy has failed. But CAM is also increasingly becoming a
      first-line intervention for some, because of the worry about the side effects of
      conventional treatments and a perception that orthodoxy has become dehumanized.
      With some exceptions, research is still in its early stages and lacks
      infrastructure. Patient satisfaction, empirical clinical outcome, and cost are
      beginning to be emphasized over mechanism of action or explanatory models. Recent
      official reports are calling for national and European-level enquiry and
      response. Future development is likely to emphasize integrative care. The
      challenge is to create better medical systems, with a whole-person emphasis,
      calling on a broader range of approaches than is currently orthodox. We seem to
      need a reunion of the art and science of medicine.

PMID- 11822633
TI  - Complementary and alternative medicine in Korea: current status and future
      prospects.
AB  - Traditional Oriental medicine has been an integral part of prevailing practice
      and belief systems throughout Korea's history. Beginning late in the nineteenth
      century, Western medical practices were introduced by Christian missionaries and
      these practices quickly supplanted traditional medicine in institutional health
      care. After the Korean War, the government revived interest in Oriental medicine
      and established colleges of Oriental medicine, in addition to supporting the
      colleges of Western medicine. A difference in standards between these medical
      traditions underlies a mistrust of complementary and alternative medicine (CAM)
      that is common among practitioners of Western medicine. Western medicine is built
      on reproducible experiments and statistical analysis, whereas complementary and
      alternative treatments are built on experience. Recent surveys show that CAM is
      widely used in Korea, with usage rates ranging from 29% to 53% among various
      patient populations. CAM also accounts for a large share of healthcare costs.
      Approximately 29% of out-of-pocket, health care expenditure in Korea is for CAM
      therapies. Both the Korean government and the medical community recognize a need
      to integrate the health care delivery system and to define the roles of
      physicians, Oriental medical doctors, and pharmacists better. To accomplish this,
      there will be a need for standards for judging the safety and effectiveness of
      treatments and consensus-building will be needed to overcome the differences
      among practitioners from various traditions and backgrounds.

PMID- 11822634
TI  - Report by David M. Eisenberg, M.D., on educational issues pertaining to
      complementary and alternative medicine in the United States.
AB  - In the second of his two presentations, David Eisenberg, M.D., addressed the
      challenge of educating today's physicians and the next generation of medical
      students in the area of complementary and alternative medicine.

PMID- 11822635
TI  - Research on complementary and alternative medicine using randomized controlled
      trials.
AB  - In 1998, the National Institutes of Health (NIH) formed the National Center for
      Complementary and Alternative Medicine (NCCAM) from what had formerly been the
      Office of Alternative Medicine. This presentation opens with a brief discussion
      on the history of the NIH and the development of CAM at the NIH before moving on
      to the work of the NCCAM. The NCCAM is moving toward an integration of CAM
      therapies into conventional medicine, when there is evidence for the value of
      CAM. One of twenty-five institutes or centers at the NIH, the NCCAM looks at
      evidence-based medicine and public health. In this context, "public health" means
      educating the public about its health. The NCCAM supports training to conduct
      research and plays an important role in disseminating information to the public
      and to health providers about what works and what is safe. This evolves into the
      concept of evidence-based medical and public-health practices, that is, making
      decisions on the basis of evidence from scientifically rigorous studies that are
      sufficiently large to provide a confident estimate of biologically and medically
      important benefits and risks. In the hierarchy of generating scientific evidence,
      randomized controlled trials are considered the "gold standard." The NCCAM
      entertains proposals for studies that come spontaneously from investigators, or,
      upon identifying an existing need that is not being met by the investigative
      community, the NCCAM can initiate a request for proposals. Every proposal is
      subjected to a rigorous application and review process. Another possible step in
      the assessment of the evidence from clinical trials is to do a systematic
      analysis of several studies to bring together all the information that is
      available. Systematic reviews of smaller studies that individually might have an
      insufficient sample size can assist in making treatment decisions, but,
      importantly, they can lead the NCCAM in the development of future, definitive
      studies. Training to conduct research is especially important to CAM. This
      presentation outlines several approaches the NCCAM has to training (see
      http://nccam.nih.gov).

PMID- 11822636
TI  - New opportunities and proven approaches in complementary and alternative medicine
      research at the National Institutes of Health.
AB  - This presentation describes some of the issues that arise when applying the
      clinical-trial approach of conventional medicine to complementary and alternative
      medicine (CAM) modalities. Conventional medicine has been making the evolution to
      using an evidence base and to making recommendations only when the evidence is
      strong. The National Center for Complementary Medicine (NCCAM), one of twenty
      five Institutes or Centers of the National Institutes of Health (NIH), is working
      to hold CAM to the same high standards, not by rejecting previous CAM research,
      but by building on that strong evidence base of what works and what is safe. The
      process for conventional drug and device development follows an orderly process
      of preclinical studies (usually on animals), phase I, phase II, and phase III
      studies (with the large human clinical trial phase taking place in phase III).
      Today, the randomized controlled trial is recognized as providing the highest
      level of scientific evidence. This conventional medicine approach to development
      is now being used to develop complementary and alternative therapies. For
      instance, the discovery and development of Taxol (Bristol-Meyers Squibb, New
      York, NY), an extract from the bark of the Pacific yew tree that is now a widely
      used chemotherapeutic agent, followed the conventional pathway to approval and
      marketing. But for most CAM products, the pathway is not so straightforward. Most
      CAM therapies are traditional therapies or new products that are already
      available to the public. Most of what is known about these therapies is of an
      anecdotal nature. There has been little isolation of the active principals from
      the crude product and there has usually been no preclinical testing. This
      presentation details various approaches and programs that address how to plan and
      conduct a rigorous clinical trial of a CAM product. And, while it takes a good
      deal of persistence and a strong focus on what are the critical principals in a
      trial, I conclude that it is possible to apply randomized controlled trials to
      most of the CAM modalities.

PMID- 11822637
TI  - A new integrated program for natural product development and the value of an
      ethnomedical approach.
AB  - There is a need for less expensive alternative therapies, especially in the
      treatment of chronic illnesses. This presentation addresses the issues inherent
      in the use of natural products in a drug-discovery or development program and
      reviews a model program developed by the U.S. National Institutes of Health (NIH)
      and administered by the Fogarty International Center at the NIH. Eighty percent
      (80%) of the world's population relies on medicinal plants for their primary
      health care. The World Health Organization has been promoting traditional
      medicine as a source of less expensive, comprehensive medical care, especially in
      developing countries. Natural products have also been successful in drug
      development. Over 50% of the best-selling pharmaceuticals in use today are
      derived from natural products. In a natural-product drug development program, it
      is the diversity of the natural products that is especially interesting. Thanks
      to technologic advances, now is a good time to be looking for new drugs in the
      natural-product arena. But there are major hurdles to overcome in a natural
      products development program, namely, time-to-lead, supply, and ownership. Time
      to-lead is complex because most natural products are mixtures or crude extracts.
      It can be very difficult to isolate the active principles and elucidate their
      structures. The difficulty of obtaining sufficient supply is often given as a
      reason for not becoming involved in natural-product drug development or
      discovery. This presentation details some ways these seeming hurdles can be
      overcome. The concept of ownership has changed dramatically in recent years.
      Until recently, genetic resources were considered to belong to no one and to
      therefore be the heritage of everyone. The United Nations Convention on
      Biodiversity and the meetings in Rio de Janeiro in 1992, redefined biodiversity
      ownership. Genetic biodiversity has a potential value and belongs to the country
      of origin. The International Conservation of Biodiversity Groups (ICBGs) was
      founded in 1992 to address such issues. This presentation discusses the
      importance of integrating efforts in conservation, economic development, and drug
      development into one program. The presentation details a collaboration that
      includes an ICBG based at the Walter Reed Army Institute of Research and its four
      partner organizations and discusses the associated programs the collaboration has
      underway.

PMID- 11822638
TI  - Demonstrating the validity of natural products as anti-infective drugs.
AB  - This presentation reviews the synthetic or classical development pathway of drug
      development and contrasts it with developing natural products as drugs. Also
      presented is an example of a traditional medicine that has been developed from a
      natural product and has become a "new/old" antiparasitic drug used in the
      treatment of malaria. The classic paradigm of synthetic drug development breaks
      down into drug discovery, drug design, preclinical studies, and clinical studies.
      This paradigm, constructed to weed out failures, results in a drug-development
      process that is high risk, time consuming, and expensive. The process requires
      screening an average of 10,000 active compounds to find a single compound that
      successfully makes its way through validation to drug approval and the
      marketplace. Following this paradigm, researchers progress from identifying a
      chemical lead to testing the compound in humans. The World Health Organization
      (WHO) Guidelines for the Assessment of Herbal Medicines are based on the
      classical guidelines and follow the classical approach to validating quality,
      safety, and efficacy--with one major difference. The starting point is to look at
      the natural product in humans. By taking into account the traditional experience
      with the product, the validation standard for safety and efficacy of natural
      products allows for the prolonged and apparently uneventful use of a substance to
      offer testimony of its safety. The reliance, then, is on experience--or what
      Western regulatory agencies would call "anecdotal information." Since most
      phytomedicines are a combination of several active ingredients, the WHO
      guidelines cover two kinds of combination products: Combinations that are already
      used in traditional medicine are considered "old" combination products. "New"
      combination products are well-known substances that are now being used in
      combination. Artemisia annua, a pervasive weed, has been referred to in Chinese
      medicine for thousands of years as a treatment for fever. In 1971, an extraction
      of artemisia yielded activity against Plasmodium berghei, a mouse model for
      malaria. The isolated compound, artemisinin, is an example of a traditional
      medicine that started out in humans, but which then provided a lead structure for
      a standard drug-development paradigm. Today, artemisinin derivatives are being
      used widely in combination therapy, especially in areas of the world where there
      is multidrug-resistant malaria.

PMID- 11822639
TI  - The physiology of mind-body interactions: the stress response and the relaxation
      response.
AB  - There are key differences between mind-body medicine and alternative medicine. A
      central tenet of mind-body medicine is the recognition that the mind plays a key
      role in health and that any presumed separation of mind and body is false.
      Alternative medicine, however, does not focus on the role of thoughts and
      emotions in health and, therefore, is separate from mind-body medicine. Also,
      while there has been little scientific research on alternative medicine, the
      literature on mind-body medicine comprises more than 2000 peer-reviewed studies
      published in the past 25 years. The groundwork for understanding the physiology
      of mind-body interactions was established by pioneering studies in the 1930s by
      Walter Cannon, and in the 1950s by Walter Hess and by Hans Selye that led to an
      understanding of the fight-or-flight response. Later work by Holmes and Rahe
      documented measurable relationships between stressful life events and illness.
      Other research has shown clinical improvement in patients treated with a placebo
      for a variety of medical problems. The effectiveness of placebo treatment can be
      interpreted as compelling evidence that expectation and belief can affect
      physiological response. Recent studies using spectral analysis and topographic
      electroencephalographic (EEG) mapping of the relaxation response demonstrate that
      by changing mental activity we can demonstrate measurable changes in central
      nervous system activity. These, and other, studies demonstrate that mind-body
      interactions are real and can be measured.

PMID- 11822640
TI  - Clinical applications of the relaxation response and mind-body interventions.
AB  - Several hundred peer-reviewed studies in the past 20 years have shown that the
      relaxation response and mind-body interventions are clinically effective in the
      treatment of many health problems that are caused or made worse by stress. Recent
      studies show that mind-body interventions may improve prognosis in coronary heart
      disease and can enhance immune functioning. It is hypothesized that mind-body
      interventions reduce sympathetic nervous system activation and increase
      parasympathetic nervous system activity, and thereby restore homeostasis.
      Researchers have also concluded that cognitive therapy is as effective, and
      possibly more effective than antidepressant medication in the treatment of major
      depression. This report provides an overview of some studies that have shown a
      beneficial role of the relaxation response and cognitive restructuring in the
      treatment of headaches, insomnia, and cardiovascular disorders. Studies to date
      suggest that mind-body interventions are effective and can also provide cost
      savings in patient treatment. It is also clear, however, that mind-body therapies
      are not panaceas, and should be used in conjunction with standard medical care.

PMID- 11822641
TI  - Report from the Universities of Lund/Malmo, London, Oxford, Klaipeda and Tartu.
      The Baltic Forum 1994-2000: a primary health care research workshop.

PMID- 11822642
TI  - Implementing evidence in Finnish primary care. Use of electronic guidelines in
      daily practice.
AB  - In Finland, electronic guidelines have provided general practitioners (GPs) with
      a source of up-to-date information at their fingertips since 1989. The
      Physician's Desk Reference and Database (PDRD) covers the majority of problems
      encountered in primary care with some 1,000 articles. These are available in
      electronic format, updated every 4 months, and as a book published in a fully
      revised edition every 2 years. Physicians use these guidelines as a routine part
      of their daily work. They seek information for both common and rare health
      problems and use it to plan diagnostic strategies as well as treatment and follow
      up. In nearly 90% of cases the doctor finds the information she needs from the
      guidelines. The electronic version is user-friendly; typically the relevant
      article is found and read in 2 min. Patients find it reassuring when their doctor
      uses guidelines to select optimal treatment. Other Nordic countries are aslo
      producing several national guidelines, but Finland has so far the widest scope
      and longest experience in this area. An English version of the PDRD guidelines
      (Evidence-Based Medicine Guidelines) is available, and a Swedish-language version
      will be completed in 2002.

PMID- 11822643
TI  - Health status and service utilisation of older people in different European
      countries.
AB  - OBJECTIVE: Care of elderly demands more and more resources. The purpose of this
      study was to compare the health of the elderly and the differences in utilisation
      of services. DESIGN: Health status was measured using the Short Form 36, the
      Barthel Index of Activities of Daily Living, the Abbreviated Mental Test and the
      Hospital Anxiety and Depression Scale. Information was also obtained on health
      and social service utilisation. SETTING: Eight European districts. SUBJECTS: 4004
      elderly aged 70-94 years were studied. RESULTS: General health perception
      measured with SF-36 was significantly better in men than in women and in elderly
      living outside institutions. Measured with the Barthel scale, the elderly living
      in the southern districts were more disabled. Women were more disabled than men.
      Depression and anxiety were common, but inadequately treated and strongly linked
      with disability. There was a north-south difference also in mental disability,
      people in the north feeling healthier. CONCLUSION: Cultural differences probably
      explain most of the differences observed. However, treating depression and
      anxiety more adequately could help elderly people to avoid early
      institutionalisation.

PMID- 11822644
TI  - Effects of a fundholding discontinuation. An Israeli health maintenance
      organization natural experiment.
AB  - OBJECTIVE: To evaluate the effects of fundholding on cost containment and after
      termination of the project. DESIGN AND SETTING: Primary care practices
      participating in the project were allocated an itemized budget. Practices assumed
      authority for hospitalization, drugs, ambulatory medical diagnostic, consultant
      services and acquisition of minor equipment. Financial incentives were offered,
      but no penalties were imposed on practices where expenditure exceeded budget.
      SUBJECTS: Nine primary care practices in southern Israel. MAIN OUTCOME MEASURE:
      Total expenditure and a breakdown of expenditure per capita. RESULTS: Fundholding
      practice expenditure was compared with expenditure in the district as a whole.
      During the study period, total expenditure in fundholding practices rose by 12%,
      whereas that of the district rose by 37%. With discontinuation of the project,
      expenditure of the designated practices returned to the original levels,
      equivalent to those of the district. CONCLUSION: Fundholding is an efficient
      method of cost-containment. The effect will be long lasting only if motivation is
      maintained.

PMID- 11822645
TI  - Implementation of guidelines in primary health care. A challenge for the
      municipal health centres in Finland.
AB  - OBJECTIVE: To assess the implementation of guidelines in Finnish primary health
      care units. DESIGN: A semi-quantitative analysis of a cross-sectional interview
      survey. SETTING: All municipal health centres in a selected region in Finland.
      SUBJECTS: Head physicians and head nurses of the 31 participating units. MAIN
      OUTCOME MEASURES: Number of guidelines adopted; methods used in the
      implementation; and the unit's estimated purposefulness in the implementation of
      guidelines. RESULTS: All health centres had adopted at least one guideline in the
      defined task areas, but only one-third of the units had implemented several
      guidelines. The implementation methods utilised were usually directive and
      passive rather than co-operative and problem-solving. Half of the units used
      training and methods involving active participation of the personnel, and in one
      third a multiprofessional approach was applied. Clients' representatives were
      hardly ever involved in the adaptation of guidelines. A quarter of the health
      centres were assessed as purposeful in their policy to implement guidelines, the
      large units being more goal-oriented than the smaller ones. CONCLUSIONS: A
      minority of health centres are goal-oriented in the adoption of guidelines and
      use versatile methods to support the implementation; this presents an important
      managerial challenge for national health care development in Finland.

PMID- 11822646
TI  - Indicators of childhood adversity in somatisation in general practice.
AB  - OBJECTIVE: To identify medical and psychosocial indicators of childhood adversity
      in somatising patients in primary care. DESIGN: Retrospective questionnaires and
      interviews. SETTING: Primary health care in The Netherlands. SUBJECTS: Three
      hundred-and-seventy-four somatising frequent attenders in 27 general practices
      between 20 and 45 years of age. MAIN OUTCOME MEASURES: Major problems in
      childhood. RESULTS: The questionnaire on childhood problems reflected acceptable
      validity against a structured interview in 77 patients (correlation 0.69);
      however, the item "abuse" was underreported in the questionnaire. Four out of
      five patients reported one or more major childhood problems. Childhood adversity
      was indicated independently by chronic difficulties in present relations and by
      genital-sexual symptoms of patients. CONCLUSION: When GPs want to take a more
      active approach towards somatisers they may show interest in the childhood and
      life story of patients, especially when patients are known with chronic
      difficulties in relations and genital-sexual symptoms.

PMID- 11822647
TI  - Doctor-patient discussions of alternative medicine for back pain.
AB  - OBJECTIVE: To document the frequency of conversations about alternative medicine
      during primary care consultations for back pain in diverse settings. DESIGN:
      "Exit interview" type patient survey. SETTINGS: General practices in Seattle,
      Washington; rural Israel; and Birmingham, England. PATIENTS: A convenience sample
      of 218 adults completing a doctor visit for back pain. MAIN OUTCOME MEASURES:
      Frequencies of doctor-patient discussions of alternative medicine. RESULTS:
      Alternative medicine was discussed in a minority of visits (US site 40%, Israel
      site 37%, UK site 14%, p < 0.05). At each site, patients initiated at least half
      of the discussions. Users were five to six times more likely to discuss
      alternative medicine with their doctor than non-users (p < 0.05 for comparison at
      each site). The percentage of patients who used alternative medicine but left the
      consultation without discussing it was similar at all sites (US site 17%, Israel
      site 23%, UK site 15%). CONCLUSIONS: Discussions of alternative medicine occurred
      in a minority of consultations for back pain although the rate varied
      considerably by site. Discussions were initiated primarily by patients who use
      it.

PMID- 11822648
TI  - HbAlc in an unselected population of 4438 people with type 2 diabetes in a Danish
      county.
AB  - OBJECTIVE: To describe the use and level of HbA1c in a large unselected Type 2
      diabetic population in Denmark. In addition, to describe the characteristics of
      the patients and the general practitioners in relation to the monitoring of
      HbA1c. DESIGN: Data were collected from public data files for the period January
      1993 to December 1997. SETTING: The County of Vejle with a background population
      of 342,597 citizens, 303,250 of whom were listed with participating general
      practitioners. PATIENTS: The Type 2 diabetic population alive and resident in the
      county on 1 January 1997. RESULTS: In a population of 4438 Type 2 diabetics, 73%
      had a minimum of one annual HbA1c measurement in 1997. No HbA1c measurement was
      associated with a long history of diabetes, diet treatment or old age. Poor
      glycaemic regulation was found in 65% of the Type 2 diabetics in 1997. Poor
      glycaemic regulation was associated with tablet or insulin treatment, age under
      70 years and long history of diabetes. The interpractice variation was huge.
      CONCLUSION: The quality of HbA1c monitoring of Type 2 diabetics needs to be
      improved. Possibilities for improvement seem to be present.

PMID- 11822649
TI  - Comparison of urinary albumin excretion rate in overnight urine and albumin
      creatinine ratio in spot urine in diabetic patients in general practice.
AB  - OBJECTIVE: To evaluate whether measurement of albumin creatinine ratio (ACR) on a
      spot urine specimen can replace a timed overnight collection of urine albumin
      excretion rate (UAER) in patients with diabetes in primary care. DESIGN: Patients
      with diabetes attending Ronvik Health Centre were asked to bring a timed
      overnight collection of urine for measurement of UAER. They were also asked to
      void a urine specimen for measurement of albumin creatinine ratio. SETTING:
      Primary health care. SUBJECTS: One-hundred-and-six persons with diabetes (47
      women, 59 men) aged 13 to 78 years. RESULTS: The sensitivity and specificity of
      ACR with cut-off values of 2.5 mg/mmol for men and 3.5 mg/mmol for women compared
      to UAER with cut-off value of 20 mg/24 h was 90%. CONCLUSIONS: Spot urine ACR
      analysed on a DCA 2000 can replace a timed (overnight) collection of urine and
      measurement of UAER when diabetic patients are reviewed in general practice. This
      simplifies procedures for the patient as a timed urine collection is no longer
      necessary. Another advantage is that the results are available after 7 min.

PMID- 11822650
TI  - From exercise and education to movement and interaction. Treatment groups in
      primary care for women with chronic muscular pain.
AB  - OBJECTIVE: To develop a group-based treatment programme in primary health care
      for women with chronic muscle pain, and adjust programme development according to
      experiences obtained by the participating women and health personnel. The aim of
      the programme was to help the women develop a tool for handling their chronic
      state of pain. The article describes and discusses experiences essential for
      elaboration of the treatment programme. DESIGN: Action research design. SETTING:
      Existing therapy groups in Stovner for women with chronic muscle pain. SUBJECTS:
      We arranged eight treatment groups, each lasting 12 weeks, and three groups
      lasting 10 months, with a total of 133 participants. MAIN OUTCOME MEASURES:
      Experiences were systematised by means of pragmatic analysis of qualitative data
      from field notes, tape recordings of focus group interviews, and video recordings
      of training and discussion groups. RESULTS: While initially the training
      programme aimed at increasing physical fitness and muscle strength, it gradually
      developed into activity based on movement with an emphasis on noticing and
      experiencing. The instruction programme initially aimed at providing information,
      and developed towards discussion groups with emphasis on mutual understanding and
      recognition. CONCLUSIONS: The training programme is now concentrated on a few,
      simple exercises and is characterised by awareness of the relationship between
      breathing and muscle tension. Groups were found to be the main pillar of the
      programme, characterised by security and a feeling of belonging with room for
      reflection and development.

PMID- 11822651
TI  - Determinants of an incorrect inhalation technique in patients with asthma or
      COPD.
AB  - OBJECTIVE: To determine the prevalence of an incorrect inhalation technique and
      to examine its determinants among primary care patients with asthma or chronic
      obstructive pulmonary disease (COPD). DESIGN: Cross-sectional study. SETTING: 28
      general practitioners in The Netherlands. SUBJECTS: 558 asthma and COPD patients,
      aged 16-75 years. MAIN OUTCOME MEASURES: Inhalation technique was assessed using
      a standardised inhaler-specific checklist. Pulmonary function assessment and
      questionnaires were used to collect data about inhaler, patient and disease
      characteristics. RESULTS: Overall, 24.2% of the patients made at least one
      essential mistake in their inhalation technique. The type of inhaler appeared to
      be the strongest independent determinant of an incorrect inhalation technique.
      Compared to patients using the Diskhaler, patients using the Rotahaler/Spinhaler,
      Turbuhaler, Metered Dose Inhaler (MDI) or Cyclohaler/Inhaler-Ingelheim were at
      significantly higher risk of making inhalation mistakes (odds ratios (OR) were
      16.08, 13.17, 11.60 and 3.27, respectively). Other significant determinants of an
      incorrect inhalation technique were low emotional quality of life (OR = 1.73) and
      being treated in a group practice (OR = 2.26). CONCLUSIONS: An incorrect
      inhalation technique is common among pulmonary disease patients in primary care.
      Our study suggests that especially patients using the Rotahaler/Spinhaler,
      Turbuhaler or MDI, patients with emotional problems and patients in a group
      practice are at increased risk for an incorrect inhalation technique.

PMID- 11822652
TI  - Experiences from an allergy prevention programme in schoolchildren in a Swedish
      community.
AB  - OBJECTIVE: To evaluate an allergy prevention programme in a community. DESIGN:
      Allergy prevention programme initiated by a special community allergy prevention
      committee and evaluation of this programme by means of a questionnaire to
      schoolchildren on repeated occasions during the period 1980 to 1998. SETTING: The
      community of Habo in Sweden with about 9500 inhabitants. MAIN OUTCOME MEASURES:
      Prevalence of allergy manifestations according to the questionnaire. RESULTS: In
      contrast to what is mostly reported, the prevalence of allergic manifestations
      seemed to decrease in the community of Habo during the observation period.
      CONCLUSION: The results indicate a benefit from an intensified allergy prevention
      programme on the local level, but additional observations from other communities
      are needed in order to draw safe conclusions about the effect of allergy
      prevention programmes.

PMID- 11822654
TI  - Meeting report: Anaerobic Protozoan Parasites, Prague, Czech Republic, July 15
      19, 2001.

PMID- 11822653
TI  - Monitoring improvement using a patient-rated depression scale during treatment
      with anti-depressants in general practice. A validation study on the Goldberg
      Depression Scale.
AB  - OBJECTIVE: To perform a pilot study on the value of the Goldberg Depression Scale
      as an instrument for monitoring improvement in depressed patients treated with
      anti-depressants in general practice. DESIGN: A comparative study using
      simultaneous ratings on the observer-based 17-item Hamilton Depression Scale and
      the patient-rated Goldberg Depression Scale. SETTING: General practice. PATIENTS:
      Twenty-one patients meeting the ICD-10 criteria of a moderate depressive episode
      were assessed at the time of inclusion and through three follow-up visits. MAIN
      OUTCOME MEASURES: Scores on the Goldberg Depression Scale compared to the
      Hamilton Depression Scale. RESULTS: An acceptable internal and external validity
      of the Goldberg Depression Scale was demonstrated. The Loevinger coefficient
      varied from 0.25 at the time of diagnosis to 0.57, 0.65 and 0.69 by visits two,
      three and four. Factor analysis identified only one general factor explaining 50%
      or more of the variants, except at visit 1. When the Goldberg Depression Scale
      was correlated to the Hamilton Depression Scales, a coefficient of 0.74 was
      obtained (p < 0.001). CONCLUSION: This pilot study indicates that the Goldberg
      Depression Scale is suitable for monitoring improvement in depressed patients
      treated in general practice. Further studies are recommended.

PMID- 11822655
TI  - The intriguing biology of Dictyostelium discoideum. Meeting report: International
      Dictyostelium Conference 2001.

PMID- 11822656
TI  - Meeting report: 7th International Phycological Congress, Thessaloniki, Greece,
      August 18-25, 2001.

PMID- 11822658
TI  - Molecular phylogeny and taxonomic revision of Chlamydomonas (Chlorophyta). I.
      Emendation of Chlamydomonas Ehrenberg and Chloromonas Gobi, and description of
      Oogamochlamys gen. nov. and Lobochlamys gen. nov.
AB  - The genus Chlamydomonas (including Chloromonas) is one of the largest green algal
      genera comprising more than 600 species. To initiate a comprehensive analysis of
      the phylogeny and systematics of the genus, we determined nuclear-encoded SSU
      rRNA sequences from 32 strains of Chlamydomonas, Chloromonas and Chlorogonium
      with emphasis on oogamous taxa and related strains, and incorporated these into
      global molecular phylogenetic analyses of 132 strains of Chlorophyceae. In
      addition, we studied the morphology and reproduction of oogamous and related
      strains by light microscopy. We recognize and designate 18 monophyletic lineages
      (clades) within the Chlorophyceae, 11 of which are confined to the CW (basal
      bodies displaced clockwise) subgroup. The majority of clades recognized within
      the Chlorophyceae do not correspond to any of the traditional classification
      systems, which are still largely based on the organization level. Strains
      assigned to Chlamydomonas and Chloromonas were found in seven different clades
      confirming the polyphyly of the two genera as presently conceived. To initiate
      the taxonomic revision of Chlamydomonas, C. reinhardtii is proposed as the
      conserved type of the genus. In consequence, species in clades other than the
      clade containing C. reinhardtii must be transferred to other genera, a process
      initiated in this contribution. The oogamous strains studied represent a
      monophyletic lineage, which is described as Oogamochlamys gen. nov. comprising
      three species (O. gigantea, O. zimbabwiensis and O. ettlii spec. nov.). The
      sister clade to Oogamochlamys consists of isogamous strains characterized by
      chloroplasts with incisions and is described as Lobochlamys gen. nov. with two
      species (L. culleus and L. segnis). Another clade is characterized by asteroid or
      perforated, parietal chloroplasts and contains the type species of Chloromonas
      (C. reticulata). Thus, the polyphyletic Chloromonas (traditionally defined as
      "Chlamydomonas without pyrenoids") can be legitimized as a monophyletic genus by
      restriction to this clade and is here emended on the basis of chloroplast
      characters (the clade contains strains with or without pyrenoids thus rejecting
      the character "absence of pyrenoids").

PMID- 11822657
TI  - Unlocking the secrets of trypanosome kinetoplast DNA network replication.

PMID- 11822659
TI  - Quantitative estimation of flagellate community structure and diversity in soil
      samples.
AB  - Heterotrophic flagellates occur in nearly all soils and, in most cases, many
      different species are present. Nevertheless, quantitative data on their community
      structure and diversity are sparse, possibly due to a lack of suitable
      techniques. Previous studies have tended to focus on either total flagellate
      numbers and biomass, or the identification and description of flagellate species
      present. With the increased awareness of the role of biodiversity and of food web
      interactions, the quantification of species within the community and their
      response to environmental change is likely to become more important. The present
      paper describes a modification of the most probable number method that allows
      such a quantification of individual flagellate morphotypes in soil samples.
      Observations were also made on the biomass of flagellate morphotypes in soil. 20
      to 25 morphotypes of heterotrophic flagellates were detectable per gram of two
      different arable soils, which were treated experimentally to test the technique.
      One of the soils was fumigated with chloroform vapour for different lengths of
      time (0, 0.5, 2 or 24 hours); this led to a reduction in the number of
      morphotypes, in the Shannon diversity index and in the evenness. The other soil
      was planted with wheat, and while rhizosphere soils contained the same
      morphotypes as bulk soil, the abundance of individual morphotypes was
      significantly different and the Shannon diversity index in rhizosphere soils was
      significantly higher. Soil influenced by an elevated CO2 level likewise differed
      significantly in morphotype abundance when compared to soil exposed to ambient
      levels of CO2. The technique recovered more than 80% of the discernible
      morphotypes and could also be used to quantify amoebal and ciliate communities in
      a similar way.

PMID- 11822660
TI  - Identification of a 41 kDa protein embedded in the biosilica of scales and
      bristles isolated from Mallomonas splendens (Synurophyceae, Ochrophyta).
AB  - Cells of the photosynthetic protist Mallomonas splendens (Synurophyceae,
      Ochrophyta) are encased within a highly patterned wall or scale case that
      consists of silicified scales and bristles. In an effort to understand the
      mechanisms that unicellular protists utilize to produce elaborate, mineralized
      structures of great complexity and hierarchical structure, we identified and
      characterized a 41 kDa protein from purified scales/bristles isolated from M.
      splendens (SP41 for Scale Protein of 41 kDa). A cDNA encoding this protein was
      isolated and sequence analysis indicated that it is a novel protein. Polyclonal
      antibodies were generated against bacterially expressed SP41 and used to localize
      the protein throughout scale and bristle morphogenesis. Immunoelectron microscopy
      confirmed the biochemical data that SP41 is a component of mature scales and
      bristles, the protein localizing to silicified components of the purified
      extracellular matrix. During scale and bristle biogenesis within the cell, SP41
      is deposited into a specialized Silica Deposition Vesicle (SDV) concomitant with
      silica deposition, a highly regulated event during scale and bristle formation.
      These results argue for SP41 playing a role in morphogenesis and/or
      silicification within the SDV during scale and bristle biogenesis.

PMID- 11822661
TI  - How dinoflagellates swim.
AB  - Dinoflagellates possess two flagella; usually these are directed perpendicular to
      one another constituting a transversal flagellum and a longitudinal, trailing
      flagellum, respectively. The transversal flagellum causes the cell to rotate
      around its length axis. The trailing flagellum is responsible for the translation
      of the cell; due to its asymmetric insertion it also causes a rotation of the
      cell around an axis perpendicular to the longitudinal axis. Together, these two
      rotational components result in a helical swimming path. Cells can vary the two
      rotational components independently as well as the translational velocity. With
      these three degrees of freedom, cells can vary the parameters of their helical
      swimming paths for steering. Dinoflagellates use this mechanism for orientation
      in chemical concentration gradients ("helical klinotaxis").

PMID- 11822662
TI  - Basal body-associated nucleation center for the centrin-based cortical
      cytoskeletal network in Paramecium.
AB  - The infraciliary lattice, a contractile cortical cytoskeletal network of
      Paramecium, is composed of a small number of polypeptides including centrins. Its
      overall pattern reflects a hierarchy of structural complexity, from assembly and
      bundling of microfilaments to formation of polygonal meshes arranged in a
      continuous network subtending the whole cell surface, with local differentiations
      in the shape and size of the meshes. To analyse how the geometry of this complex
      network is generated and maintained, we have taken two approaches. Firstly, using
      monoclonal antibodies raised against the purified network, we have shown that all
      the component polypeptides colocalize, in agreement with previous biochemical
      data indicating that the infraciliary lattice is formed of large complexes
      comprising all the component polypeptides. Secondly, by taking advantage of
      different experimental conditions leading to disassembly of the network, we have
      followed its reassembly. Cytological analysis of the process revealed 1) that the
      network regrows exclusively from specific infraciliary lattice organizing centers
      (ICLOC), precisely localized near each basal body and, 2) that the global
      organization is not precisely controlled by genetic information but by the basal
      body pattern. Finally, slight ultrastuctural differences between reassembled and
      control lattices suggest that the organization of the filament bundles is partly
      templated by that of the preexisting ones.

PMID- 11822663
TI  - Biodiversity of terrestrial protozoa appears homogeneous across local and global
      spatial scales.
AB  - Free-living microbes are by far the most abundant group of organisms in the
      biosphere, yet estimates of global species richness remain nebulous, and there is
      no consensus regarding the likely geographical distribution of species. Both
      uncertainties are addressed by the suggestion that the vast abundance of microbes
      may drive their ubiquitous random dispersal; for this would also make it likely
      that global species richness is relatively low. Here we test the idea of
      ubiquitous dispersal of testate amoebae and ciliates living in soil. We analysed
      their abundance and species richness in 150 soil samples collected from the one
      hectare grassland site at Sourhope in Scotland, and in comparable published data
      from 1500 soil samples collected worldwide. Following taxonomic revision and
      removal of synonyms, there remained a total of 186 taxa (91 testate and 95
      ciliate) recorded from both Sourhope and other places in the world. A fundamental
      pattern of random spatial distribution of species was revealed in species that
      are relatively rare. This probably arises from random dispersal, for when
      localised population growth occurs, the distributions become aggregated, as in
      virtually all metazoan species. We find no evidence for geographically-restricted
      protozoan morphospecies at spatial scales of 4 m2, 10,000 m2, or worldwide.
      Species that are locally rare or abundant are similarly rare or abundant on a
      global scale. Approximately one third of the global diversity of soil protozoa
      was found at the one-hectare grassland site in Scotland, but this is a minimum
      figure, for recorded species richness is proportional to sampling effort, as
      shown here.

PMID- 11822664
TI  - Anisomorphic cell division by African trypanosomes.
AB  - In the bloodstream of a mammalian host, African trypanosomes are pleomorphic; the
      shorter, non-proliferative, stumpy forms arise from longer, proliferative,
      slender forms with differentiation occurring via a range of morphological
      intermediates. In order to investigate how the onset of morphological change is
      co-ordinated with exit from the cell cycle we first characterized slender form
      cell division. Outgrowth of the new flagellum was found to occur at a linear
      rate, so by using outgrowth of the new flagellum as a temporal marker of the cell
      cycle we were able determine the order in which single copy organelles (nucleus,
      kinetoplast and mitochondrion) were segregated. We also found that flagellar
      length was an effective marker of the slender to stumpy differentiation and were,
      therefore, able to study both cell division and differentiation. When these
      differentiating cells were compared to cells undergoing proliferative cell
      division, they were found to be anisomorphic--showing discernible differences not
      only in the length of their new flagella but also in the shape and size of the
      cells and their nuclei.

PMID- 11822665
TI  - A love 50 years long--professor V. A. Dogiel as a protistologist.

PMID- 11822666
TI  - A siderophore peptide synthetase gene from plant-growth-promoting Pseudomonas
      putida WCS358.
AB  - Under iron limiting conditions, Pseudomonas putida WCS358 produces and secretes a
      fluorescent siderophore called pseudobactin 358 which consists of a nonapeptide
      linked to a fluorescent dihydroxy quinoline moiety. Previous studies have
      identified a major gene cluster involved in pseudobactin 358 biosynthesis and
      several regulators responsible for the activation of biosynthetic genes under
      iron starving conditions. In this study, we identified the promoter transcribing
      the pseudobactin 358 synthetase gene. Promoter deletion experiments have
      demonstrated that the DNA region downstream of the initiation of transcription
      site is necessary for proper promoter functioning. This promoter controls the
      expression of a gene designated ppsD which encodes a 2,247-residue protein, PpsD,
      which has a predicted molecular weight of 247,610 Da and contains two highly
      homologous domains of approximately 1000 amino acids each. ppsD::Tn5 mutants of
      strain WCS358 are unable to synthesise pseudobactin 358 and can be complemented
      when ppsD is provided in trans. It is concluded that ppsD is a peptide synthetase
      involved in the biosynthesis of the peptide moiety of pseudobactin 358. PpsD
      displays a very high degree of similarity (52% aa identity) with PvdD from P.
      aeruginosa, a non-ribosomal peptide synthetase involved in the biosynthesis of
      pyoverdine, the fluorescent siderophore produced by P. aeruginosa. It also
      displayed homology with other peptide synthetases from other micro-organisms
      involved in the biosynthesis of siderophores and peptide antibiotics.

PMID- 11822667
TI  - Viability of the nonculturable Vibrio cholerae O1 and O139.
AB  - Vibrio cholerae is capable of transforming into a viable but nonculturable (VBNC)
      state, and, in doing so, undergoes alteration in cell morphology. In the study
      reported here, Vibrio cholerae O1 and O139 cells were maintained in laboratory
      microcosms prepared with 1% Instant Ocean and incubated at 4 degrees C, i.e.,
      conditions which induce the VBNC state. Cells were fixed at different stages
      during entry into the VBNC state and, when no growth was detectable on solid or
      in liquid media, the ultrastructure of these cells was examined, using both
      transmission and scanning electron microscopy. As shown in earlier studies, the
      cells became smaller in size and changed from rod to ovoid or coccoid morphology,
      with the central region of the cells becoming compressed and surrounded by denser
      cytoplasm. Because the coccoid morphology, indicative of the VBNC state is common
      for Vibrio cholerae in the natural environment, as well as in starved cells
      (Baker et al., 1983; Hood et al., 1986) viability of the coccoid, viable but
      nonculturable cell was investigated. The percentage of coccoid (VBNC) cells
      showing metabolic activity and retention of membrane integrity was monitored
      using direct fluorescence staining (LIVE/DEAD BacLight Bacterial Viability kit),
      with 75 to 90% of the viable but nonculturable coccoid cells found to be
      metabolically active by this test. Furthermore, the proportion of actively
      respiring cells, using the redox dye, 5-cyano-2, 3-ditolyl tetrazolium chloride
      (CTC), relative to total cells, the latter determined by DAPI staining, ranged
      from 10 to 50%. VBNC coccoid cells retained the antigenic determinants of Vibrio
      cholerae O1 and O139, respectively, evidenced by positive reaction with
      monoclonal fluorescent antibody. Viability was further established by
      susceptibility of the VBNC cells to chlorine, copper sulfate, zinc sulfate, and
      formaldehyde. Since retention of cell membrane integrity is a determining
      characteristic of viable cells, DNA was extracted from VBNC cells in microcosms
      maintained for two months and for one year. Conservation of cholera toxin and
      toxin-associated genes, ctxA, toxR, tcpA, and zot in chromosomal DNA of VBNC
      cells was demonstrated using PCR and employing specific primers. It is concluded
      that not only do VBNC V cholerae O1 and O139 retain viability up to one year, but
      genes associated with pathogenicity are retained, along with chromosomal
      integrity.

PMID- 11822668
TI  - Accumulation of osmoprotectants and lipid pattern modulation in response to
      growth conditions by Halomonas pantelleriense.
AB  - The effects of salinity, growth temperature, pH and composition of the medium on
      the accumulation of intracellular organic solutes, by nuclear magnetic resonance
      spectroscopy (NMR) in Halomonas pantelleriense were examined. The modulation of
      lipid pattern in different growth conditions was also reported. H. pantelleriense
      accumulated glycine betaine, ectoine, hydroxyectoine and glutamate. The type of
      osmoprotectant and the relative proportion depended on growth conditions. The
      main lipids identified by NMR studies were 1,2 diacylglycero-3
      phosphorylethanolamine (PEA), 1,2 diacylglycero-3-phosphoryl-glycerol (PG) and
      cardiolipin, (DPG). The predominant fatty acids were C16:0 and C18:1, minor fatty
      acids were C16:1 and C18:0. The relative percentage of polar lipids and fatty
      acids were affected by growth conditions.

PMID- 11822669
TI  - Clostridium hathewayi sp. nov., from human faeces.
AB  - A strictly anoxic, Gram-positive, sporeforming, rod-shaped bacterium was isolated
      from a chemostat inoculated with human faeces. The bacterium used carbohydrate as
      fermentable substrates, producing acetate, ethanol, carbon dioxide and hydrogen
      as the major products of glucose metabolism, and possessed a G + C content of
      50.7 to 50.9 mol%. Comparative 16S rRNA gene sequencing showed that the
      unidentified bacterium represents a previously unrecognised sub-line within the
      Clostridium coccoides rRNA group of organisms. The nearest relatives of the
      unknown bacterium corresponded to Clostridium algidixylanolyticum, C.
      aerotolerans, C. celerecrescens, C. indolis, C. sphenoides, C. methoxybenzovorans
      and C. xylanolyticum but 16S rRNA sequence divergence values of >4% demonstrated
      that it represents a novel species. Based on the presented findings a new
      species, Clostridium hathewayi, is described. The type strain of Clostridium
      hathewayi is DSM = 13479T (= CCUG 43506 T).

PMID- 11822670
TI  - Characterization of some strains from human clinical sources which resemble
      "Leptotrichia sanguinegens": description of Sneathia sanguinegens sp. nov., gen.
      nov.
AB  - Three strains of a gram-negative, blood or serum requiring, rod-shaped bacterium
      recovered from human clinical specimens were characterised by phenotypic and
      molecular taxonomic methods. Comparative 16S rRNA gene sequencing showed the
      unknown rod-shaped strains are members of the same species as some fastidious
      isolates recovered from human blood specimens and previously designated
      "Leptotrichia sanguinegens". Based on phylogenetic and phenotypic evidence, it is
      proposed that the isolates from human sources be classified in a new genus
      Sneathia, as Sneathia sanguinegens gen. nov., sp. nov. The type strain of
      Sneathia sanguinegens is CCUG 41628T.

PMID- 11822671
TI  - Methanosarcina lacustris sp. nov., a new psychrotolerant methanogenic archaeon
      from anoxic lake sediments.
AB  - A new psychrotolerant methanogenic archaeon strain ZS was isolated from anoxic
      lake sediments (Switzerland). The cells of the organism were non-motile cocci,
      1.5-3.5 microm in diameter. The cells aggregated and formed pseudoparenchyma. The
      cell wall was Gram-positive. The organism utilized methanol, mono-, di-,
      trimethylamine and H2/CO2 with methane production. The temperature range for
      growth was 1-35 degrees C with an optimum at 25 degrees C. The DNA G+C content of
      the organism was 43.4. mol%. Analysis of the 16S rRNA gene sequence showed that
      strain ZS was phylogenetically closely related to members of the genus
      Methanosarcina, but clearly differed from all described species of this genus
      (95.6-97.6% of sequence similarity). The level of DNA-DNA hybridization of strain
      ZS with Methanosarcina barkeri and Methanosarcina mazei was 15 and 31%,
      respectively. Based on the results of physiological and phylogenetic studies
      strain ZS can be assigned to a new species of the genus Methanasarcina. The name
      Methanosarcina lacustris sp. nov. is proposed. The type strain is ZS (= DSM
      13486T, VKM B-2268).

PMID- 11822672
TI  - Classification of a Brevundimonas strain detectable after PCR with a Helicobacter
      specific primer pair.
AB  - In a study for the isolation of new Helicobacter strains, biopsy samples were
      taken from the gastric mucosa of dogs and subjected to PCR amplification using a
      Helicobacter-specific primer pair (H276f and H676r, directed to the 16S rDNA) to
      identify members of this genus in the specimens. From one Helicobacter positive
      sample, a bacterial strain was isolated which displayed a characteristic band
      after PCR amplification with the Helicobacter-specific primer pair. The isolate
      designated H2/98-FUNDUS was motile, oxidase-, catalase- and aminopeptidase
      positive and grew only under microaerophilic conditions at 37 degrees C. The
      bacterium was classified by a polyphasic approach, including analysis of the
      isoprenoid quinones, fatty acids, polar lipids and partial 16S rDNA sequence.
      Analysis of the 16S rDNA sequence (1003 bases) indicated that the strain H2/98
      FUNDUS is a member of the genus Brevundimonas and most closely related to
      Brevundimonas aurantiaca DSM 4731T (99.5% sequence similarity). Isolate H2/98
      FUNDUS contained a predominant ubiquinone Q-10 and a fatty acid profile with the
      major compounds C18:1 and C16:0. In the polar lipid extract,
      phosphatidylglycerol, six unknown phospholipids, one unknown phosphoglycolipid,
      two unknown glycolipids and two unknown aminolipids were detected. All these
      results indicate that H2/98-FUNDUS represents a new member of the genus
      Brevundimonas which gives a positive signal upon PCR employing the Helicobacter
      specific primer pair.

PMID- 11822673
TI  - Fatty acid profiles of nitrite-oxidizing bacteria reflect their phylogenetic
      heterogeneity.
AB  - The fatty acid profiles of all described species of the nitrite-oxidizing genera
      Nitrobacter, Nitrococcus, Nitrospina and Nitrospira were analyzed. The four
      genera had distinct profiles, which can be used for the differentiation and
      allocation of new isolates to these genera. The genus Nitrobacter is
      characterized by vaccenic acid as the main compound with up to 92% of the fatty
      acids and the absence of hydroxy fatty acids. The genus Nitrococcus showed cis-9
      hexadecenoic acid, hexadecanoic acid and vaccenic acid as main parts. Small
      amounts of 3-hydroxy-dodecanoic acid were detected. The genus Nitrospina
      possessed tetradecanoic acid and cis-9-hcxadecenoic acid as main compounds, also
      3-hydroxy-hexadecanoic acid was detected for this genus. The genus Nitrospira
      showed a pattern with more variations among the two described species. These
      organisms are characterized by the cis-7 and cis-11-isomers of hexadecenoic acid.
      For Nitrospira moscoviensis a specific new fatty acid was found, which
      represented the major constituent in the fatty acid profiles of autotrophically
      grown cultures. It was identified as 11-methyl-hexadecanoic acid. Since this
      compound is not known for other bacterial taxa, it represents a potential lipid
      marker for the detection of Nitrospira moscoviensis relatives in enrichment
      cultures and environmental samples. A cluster analysis of the fatty acid profiles
      is in accordance with 16S rRNA sequence-based phylogeny of the nitrite-oxidizing
      bacteria.

PMID- 11822674
TI  - Taxonomic studies of predatory bdellovibrios based on 16S rRNA analysis,
      ribotyping and the hit locus and characterization of isolates from the gut of
      animals.
AB  - The aim of our study was to obtain data for the molecular characterization of
      bdellovibrio bacteria, which were recently split into the genus Bdellovibrio and
      the newly designated genus Bacteriovorax. We determined the 16S rDNA sequences of
      five reference strains and performed a phylogenetic analysis including published
      16S rRNA sequences of bdellovibrios. A comparison of the secondary structure
      showed significant differences in two regions of the 16S rRNAs of the species
      Bdellovibrio bacteriovorus, Bacteriovorax starrii, and Bacteriovorax stolpii. In
      addition, ribotyping techniques gave specific hybridization patterns and revealed
      that two rRNA operons are present in the investigated strains. A hybridization
      probe derived from the genetic locus hit, associated with the host independent
      (HI) phenotype of B. bacteriovorus, was found to be specific for this species.
      Sequence comparison of the hit locus revealed few base pair changes between host
      independent (HI) and host dependent (HD) strains. Ribotyping and hybridization
      experiments using the hit probe were applied to characterize bdellovibrio strains
      isolated from the gut of animals and humans and one isolate from sewage.

PMID- 11822675
TI  - Metschnikowia fructicola, a new ascosporic yeast with potential for biocontrol of
      postharvest fruit rots.
AB  - A new ascosporic yeast, Metschnikowia fructicola (type strain NRRL Y-27328, CBS
      8853), is described and was isolated from grapes grown in central Israel.
      Preliminary tests indicate the new species has biocontrol activity against
      Botrytis rot of stored grapes. Phylogenetic analysis of domain D1/D2 26S rDNA
      sequences showed M. fructicola to be a sister species of M. pulcherrima.

PMID- 11822676
TI  - Single-enzyme amplified fragment length polymorphism and its applicability for
      Salmonella epidemiology.
AB  - Amplified fragment length polymorphism (AFLP) is a PCR-based DNA fingerprinting
      technique whereby restriction fragments may be visualized without prior knowledge
      of nucleotide sequences. In AFLP analysis, bacterial genomic DNA is digested with
      a restriction enzyme and ligated to adapter oligonucleotides. A subset of DNA
      fragments are then amplified using primers which contain adapter-defined
      sequences. Selective amplification is achieved by the use of primers containing
      adapter-defined sequences with one additional arbitrary nucleotide. We used four
      primers complementary to the adapter sequence, but each differing in the final 3'
      base that extended into the fragment DNA. The usefulness of these primers for
      fingerprinting Salmonella enterica was assessed in a hierarchical manner. Using a
      single-enzyme approach (SAFLP) we have used this method to fingerprint 30 strains
      of S. enterica, belonging to 14 different serotypes. SAFLP profiles derived from
      Hind III fragments differentiated between the serotypes. In addition, SAFLP
      profiles for each serotype differentiated between the phage types and individual
      strains. The technique is significantly faster to perform than other DNA-based
      methods and has given reproducible and discriminatory results. This hierarchical
      SAFLP technique may provide a valuable addition to existing methods for the DNA
      fingerprinting of S. enterica for epidemiological studies.

PMID- 11822677
TI  - DNA isolation protocols affect the detection limit of PCR approaches of bacteria
      in samples from the human gastrointestinal tract.
AB  - A major concern in molecular ecological studies is the lysis efficiency of
      different bacteria in a complex ecosystem. We used a PCR-based 16S rDNA approach
      to determine the effect of two DNA isolation protocols (i.e. the bead beating and
      Triton-X100 method) on the detection limit of seven feces-associated bacterial
      species of different genera. Glycogen was used in these protocols to improve the
      precipitation of small concentrations of DNA in ethanol without affecting the
      sequential procedures. The PCR detection limit of 16S rDNA amplicons on agarose
      gel from the seven strains tested varied between 8.0 (+/- 1.3) x 10(4) and 4.3
      (+/- 1.6) x 10(6) cells for the bead beating method, and between 8.0 (+/- 1.3) x
      10(4) and 5.4 (+/- 0.7) x 10(8) cells for the Triton X-100 method. These large
      differences are most like due to the difference in cell lysis efficiency, since a
      competitive PCR experiment did not indicate any preference for gram negative, low
      G+C gram positive or high G+C gram positive bacteria. Denaturing gradient gel
      electrophoresis (DGGE) analysis was performed to investigate the effect of both
      DNA isolation protocols on the lysis efficiency of bacteria in fecal samples. A
      higher diversity in fecal samples was observed with the bead beating method than
      with the Triton-X100 method. Bands in the bead beating method-derived DGGE
      profiles corresponding to bands of cloned sequences of the Clostridium coccoides
      Eubacterium rectale group and uncultured Fusobacterium prausnitzii were absent or
      had low intensity in the Triton X-100 method-derived profiles. The applicability
      of the bead beating method was further investigated by analyzing biopsy samples
      from the human colon which contain approximately 10(6) cells.

PMID- 11822678
TI  - Phenotypic and genotypic identification of staphylococci isolated from wild small
      mammals.
AB  - 229 strains of Staphylococcus isolated from the intestines of wild small mammals
      (Insectivora and rodents) were analysed by phenotypic tests and 16S-23S rDNA
      intergenic spacer PCR amplification (ITS-PCR). Based on the results of three
      methods (phenotypical tests, API numerical profiles and ITS-PCR) 65.5% of all
      staphylococcal strains could be identified. The remaining strains were compared
      by cluster analysis with reference and identified strains. It is quite possible
      that, a part of unidentified strains represent hitherto undescribed species, all
      the more as their ITS types were not found among other members of the genus
      Staphylococcus. Moreover, the results show that small mammals provides a suitable
      new habitat for certain staphylococci.

PMID- 11822679
TI  - 16S rDNA sequence analysis of bacterial isolates from biodeteriorated mural
      paintings in the Servilia tomb (Necropolis of carmona, Seville, Spain).
AB  - Bacteria were isolated from damaged mural paintings of the Servilia tomb
      (necropolis of Carmona, Seville, Spain). Selected strains, representative for
      different clusters of isolates with similar fatty acid profiles, were analysed by
      16S rDNA sequence analysis. Bacillus is the dominant genus among the isolates:
      members of the rRNA species complexes of B. megaterium, B. pumilus and B. firmus
      were found as well as several other Bacillus species. One group of halotolerant
      isolates falls in the Bacillus sensu lato group, with closest relatedness to the
      genera Salibacillus and Virgibacillus. Other genera found are Artbrobacter,
      Micrococcus, Streptomyces, Sphingomonas, Paenibacillus, and a genus closely
      related to Paracraurococcus. Many isolates showed low 16S rDNA sequence
      similarities with the closest related database entries, a strong indication for
      the presence of several new species among the isolates.

PMID- 11822680
TI  - Rapid parallel detection of hygienically relevant microorganisms in water samples
      by PCR and specific hybridization in microtiter plates.
AB  - A molecular biological test protocol for the parallel detection of enterococci
      and Pseudomonas aeruginosa in drinking water was developed. Amplicons labelled
      with digoxigenin during PCR were hybridized to specific 23S rDNA targeted
      oligonucleotide probes immobilized in microtiter plates. Detection was performed
      by addition of anti-digoxigenin-peroxidase-conjugate and chromogenic substrate.
      Specificity of the probes was evaluated by using pure cultures. First evaluation
      data with natural water samples in comparison to conventional microbiological
      analysis according to the German Drinking Water Regulation showed good agreement.
      Its feasible and rapid performance should be advantageous for use in routine
      drinking water quality control. Further comparative evaluation studies need to be
      undertaken to determine the true applicability for routine testing of water
      samples.

PMID- 11822681
TI  - Pyrolysis mass spectrometry (PyMS) and 16S-23S rDNA spacer region fingerprinting
      suggests the presence of novel acinetobacters in activated sludge.
AB  - Screening of large numbers of Acinetobacter spp. from activated sludge systems
      with Pyrolysis Mass Spectrometry (PyMS) showed that many did not cluster tightly
      with the currently described genomic species which have been obtained mainly from
      clinical sources. Selected isolates were then genotypically fingerprinted using
      their 16S-23S rDNA spacer region, and again the data revealed considerable
      differences in the genomic fingerprints of many of these activated sludge
      isolates to the predominantly clinical genomic species. In fact, few could be
      identified from them. The possibility that the current speciation within this
      genus is not adequate to encompass all these environmental isolates is addressed
      in relation to the methods used to study the population dynamics of Acinetobacter
      in activated sludge.

PMID- 11822682
TI  - Characterisation of IS153, an IS3-family insertion sequence isolated from
      Lactobacillus sanfranciscensis and its use for strain differentiation.
AB  - An insertion sequence has been identified in the genome of Lactobacillus
      sanfranciscensis DSM 20451T as segment of 1351 nucleotides containing 37-bp
      imperfect terminal inverted repeats. The sequence of this element encodes two out
      of phase, overlapping open reading frames, orfA and orfB, from which three
      putative proteins are produced. OrfAB is a transframe protein produced by -1
      translational frame shifting between orf A and orf B that is presumed to be the
      transposase. The large orfAB of this element encodes a 342 amino acid protein
      that displays similarities with transposases encoded by bacterial insertion
      sequences belonging to the IS3 family. In L. sanfranciscensis type strain DSM
      20451T multiple truncated IS elements were identified. Inverse PCR was used to
      analyze target sites of four of these elements, but except of their highly AT
      rich character not any sequence specificity was identified so far. Moreover, no
      flanking direct repeats were identified. Multiple copies of IS153 were detected
      by hybridization in other strains of L. sanfranciscensis. Resulting hybridization
      patterns were shown to differentiate between organisms at strain level rather
      than a probe targeted against the 16S rDNA. With a PCR based approach IS153 or
      highly similar sequences were detected in L. acidophilus, L. casei, L.
      malefermentans, L. plantarum, L. hilgardii, L. collinoides L. farciminis L. sakei
      and L. salivarius, L. reuteri as well as in Enterococcus faecium, Pediococcus
      acidilactici and P. pentosaceus.

PMID- 11822683
TI  - Taxonomic study on nonpathogenic streptomycetes isolated from common scab lesions
      on potato tubers.
AB  - Numerical analysis was carried out to compare sixteen nonpathogenic actinomycetes
      isolated from common scab lesions on potato tubers with Streptomyces scabiei type
      strain as well as with other streptomycete groups. These isolates were divided
      into two classes according to their level of similarity with S. scabiei. Isolates
      resembling S. scabiei were associated with S. griseoruber or with S.
      violaceusniger while isolates exhibiting less than 61% of similarity with S.
      scabiei were phenotypically related to S. albidoflavus or to S. atroolivaceus.
      Sequence of the 16S rRNA gene of each isolate was obtained and compared against
      the GenBank nucleotide database. No significant match could be established
      between the sequences of two potato isolates and the ones available in the
      GenBank database. The other isolates were closely related with S. setonii (S.
      griseus), S. mirabilis, S. fimbriatus, S. violaceoruber, S. melanosporofaciens
      and S. thermocarboxydus.

PMID- 11822684
TI  - High prevalence of Yersinia enterocolitica 4:O3 on pig offal in southern Germany:
      a slaughtering technique problem.
AB  - Prevalence and contamination routes of pathogenic Yersinia enterocolitica were
      studied in Southern Germany. Tonsil and faeces samples of 50 fattening pigs, 140
      offal samples and 120 minced meat samples were examined. Pig and offal samples
      were collected from a slaughterhouse approved by the European Union, and minced
      meat samples from two large meat factories. Yersinia enterocolitica was isolated
      using direct plating, overnight enrichment and selective enrichment in MRB and
      ITC broth. The isolates were bio- and serotyped, and pathogenicity was studied
      using two plasmid-encoded virulence markers: calcium dependence and Congo red
      absorption. The genotypes were studied with pulsed-field gel electrophoresis
      using NotI enzyme. Prevalence of pathogenic Y. enterocolitica 4:O3 was 60% and
      10% in tonsils and faeces of fattening pigs, respectively. Besides tonsils,
      prevalence of pathogenic Y. enterocolitica 4:O3 was also high in other pluck set
      samples, including tongues, lungs, hearts, diaphragms and livers. However, the
      highest isolation rate was obtained from the tonsils. Kidneys, which were not
      attached to the pluck set and did not hang together with tonsils on the rack, had
      the lowest isolation rate. Yersinia enterocolitica 4:O3 was isolated from 12% of
      minced meat samples. A total of 25 NotI profiles were obtained from porcine
      samples. The most common genotype, NBI, found in tonsils was also the most common
      type recovered from offal and minced meat samples. The high contamination rate of
      tonsils, and the indistinguishable NotI profiles obtained from tonsils and offal
      indicate that the tonsils contaminate offal when they are removed and hung on the
      rack together. When the head, with the tonsils and tongue, is not removed prior
      to evisceration and is not handled and inspected separately, it is difficult to
      control the spread of Y. enterocolitica 4:O3 from tonsils to the carcass, and
      subsequently, to meat.

PMID- 11822685
TI  - Taxonomic study of extreme halophilic archaea isolated from the "Salar de
      Atacama", Chile.
AB  - A large number of halophilic bacteria were isolated in 1984-1992 from the Atacama
      Saltern (North of Chile). For this study 82 strains of extreme halophilic archaea
      were selected. The characterization was performed by using the phenotypic
      characters including morphological, physiological, biochemical, nutritional and
      antimicrobial susceptibility test. The results, together with those from
      reference strains, were subjected to numerical analysis, using the Simple
      Matching (S(SM)) coefficient and clustered by the unweighted pair group method of
      association (UPGMA). Fifteen phena were obtained at an 70% similarity level. The
      results obtained reveal a high diversity among the halophilic archaea isolated.
      Representative strains from the phena were chosen to determine their DNA base
      composition and the percentage of DNA-DNA similarity compared to reference
      strains. The 16S rRNA studies showed that some of these strains constitutes a new
      taxa of extreme halophilic archaea.

PMID- 11822686
TI  - Top ten list.

PMID- 11822687
TI  - Implantable electrical stimulation in high-risk hindfoot fusions.
AB  - The risk of nonunion in both the ankle and subtalar joints has been reported as
      high as 41% and 16%, respectively. Several factors have been reported to
      significantly increase the incidence of nonunion: smoking, previous nonunion,
      osteonecrosis, history of infection, fracture type, and major medical problems. A
      single surgeon's experience is retrospectively reviewed. Thirteen patients who
      were identified as high risk for non-union had an implantable electrical
      stimulator placed at the time of their ankle or hindfoot fusion along with bone
      grafting. Three ankle, two subtalar, six tibiotalocalcaneal, and two
      tibiocalcaneal fusions were performed. All 13 patients had a minimum of two major
      risk factors for non-union. Of the 13 patients, 11 were active smokers and five
      of 13 had three or more major risk factors. At a minimum of one year follow-up
      (average, 24.6 months), successful fusion was achieved in 12 of 13 (92%)
      patients. Pain scores improved from a mean of 8.5 points preoperatively (range, 7
      to 10) to a mean of 1.9 points postoperatively (range, 1 to 6), while the
      preoperative mean modified AOFAS score of 31.2 points (range, 15 to 55) improved
      to 85.4 points (range, 45 to 100) postoperatively. The improvement was
      statistically significant at p<0.01. Eleven of 13 patients (85%) ranked their
      pain as a 1 or 2 out of 10, and achieved a modified AOFAS score of 80 or better.
      No additional procedures were done to achieve fusion. Four patients developed
      superficial wound infections requiring local wound care. The subcutaneous battery
      pack was bothersome to eight of 13 patients, painful to one, and removed in four
      patients. The results suggest that electrical implantable stimulation may be a
      useful adjunct to rigid internal fixation and bone grafting for ankle and
      hindfoot fusions in high-risk patients.

PMID- 11822688
TI  - Insertional Achilles tendinosis: surgical treatment through a central tendon
      splitting approach.
AB  - Twenty-two heels in 21 patients treated surgically for a primary diagnosis of
      insertional Achilles tendinosis were reviewed on the basis of preoperative and
      postoperative examinations, office records, and a comprehensive questionnaire
      administered to each subject. Each patient underwent surgical treatment using a
      midline-posterior skin incision combined with a central tendon splitting approach
      for debridement, retrocalcaneal bursectomy, and removal of the calcaneal bursal
      projection as necessary. The findings at surgery revealed involvement of the
      middle third of the insertion in 21 of 22 cases with only one patient manifesting
      isolated lateral involvement. Thirteen of 22 had an associated prominent
      calcaneal bursal projection and four of 22 a superficially inflamed bursa. Three
      patients required reinsertion of the tendo Achilles via drill holes and one
      underwent augmentation with a plantaris tendon. Operative findings and
      complications were reported. Eight male and 13 female patients underwent 22
      procedures (one case bilaterally) with an average follow-up of 33 months.
      Preoperative symptoms include presence of symptoms over a range of three months
      to two years and pain associated with activities of daily living (17 of 22),
      limitation of regular activities (six of 22), and pain present at rest in six of
      22. Postoperatively, 20 of 22 patients were able to return to work or routine
      activities by three months; only 13 of 22 were completely pain free. Only 13 of
      22 also claimed that they were able to return to unlimited activities. Overall,
      there was an 82% (18 of 22) satisfaction rate with surgery and 77% (17 of 22)
      stated they would have the surgery again.

PMID- 11822689
TI  - The effect on ankle dorsiflexion of gastrocnemius recession.
AB  - Gastrocnemius equinus contracture has been suggested as an etiologic factor in
      mechanical diseases of the foot and ankle and in ulcer formation in the foot. The
      purpose of this study is to assess the correction in ankle dorsiflexion that can
      be achieved with a gastrocnemius recession. An isolated gastrocnemius release
      (Strayer procedure) was performed on 26 legs, in 20 consecutive patients, for
      clinically significant gastrocnemius equinus contracture. Ankle dorsiflexion was
      assessed using a validated electrogoniometer. Ankle dorsiflexion was recorded
      with the knee straight and with the knee bent. Measurements were recorded
      preoperatively, and immediately postoperatively. Measurements at an average of
      55.0 days postsurgery (range, 37 to 128 days) were performed on 20 legs (15
      patients). RESULTS: Average preoperative ankle dorsiflexion with the knee
      straight was 5.1 degrees. Average preoperative ankle dorsiflexion with the knee
      bent was 22.8 degrees. Immediately following surgery the average ankle
      dorsiflexion with the knee straight was 23.2 degrees. The average correction was
      18.1 degrees and this increase was significant (p < 0.0001.) In the 15 patients
      (20 legs) available for follow-up, the increase in ankle dorsiflexion with the
      knee straight was maintained (average: 24.9 degrees). Patients with gastrocnemius
      contracture who underwent an isolated gastrocnemius release increased their ankle
      dorsiflexion (knee straight) by an average of 18.1 degrees with postoperative
      ankle dorsiflexion (knee straight) being equivalent (23.2 and 22.8 degrees) to
      preoperative ankle dorsiflexion (knee bent). This correction appears to be
      maintained (23.2 vs. 24.9 degrees) at short-term follow-up.

PMID- 11822690
TI  - CT analysis of hindfoot alignment in chronic lateral ankle instability.
AB  - A prospective case-control study was performed comparing axial and coronal CT
      scan images of 11 patients (14 ankles) with chronic lateral instability and 12
      controls. Scans were performed in a standardized fashion to simulate weight
      bearing. Nine measurements to evaluate the alignment of the hindfoot and forefoot
      were made on two occasions by two observers. The blinded images were read in
      order of assigned random number. The angle between the calcaneus and the vertical
      plane showed a statistically significant difference between patients (6.4 +/- 4
      degrees varus from vertical) and controls (2.7 +/- 5 degrees) using unpaired
      ANOVA (p < 0.01). Intra-observer (R2 = 0.49 +/- 0.19) and interobserver (R2 =
      0.71 +/- 0.13) variation showed moderate reliability across all measurements.
      This study demonstrates a method to evaluate hindfoot varus on CT scan. Many
      factors have been studied (e.g., proprioception) as the cause for recurrent
      instability, and this is the first time, to our knowledge, that an anatomic cause
      has been demonstrated. Although calcaneal osteotomy is clearly not indicated
      routinely, it may have a role in correcting extreme varus, which may contribute
      to failed ligament reconstruction in patients with ankle instability.

PMID- 11822691
TI  - Arch height and lower limb pain: an adult civilian study.
AB  - Flexible flatfeet in children are still treated with orthotics and operative
      procedures by some physicians who believe such treatment will prevent disability
      in adult life. Opponents of treatment cite military studies that show flexible
      flatfeet are not a source of disability in soldiers. Because no study of adult
      civilians relating arch configuration and pain have been reported, this study was
      undertaken. Ninety-nine adult male and female physically active grocery-store
      employees were studied. Half-weight-bearing footprints were made, and leg and
      foot pain questionnaires were scored for each subject. No relationship was found
      between arch configuration and pain scores. This study suggests that in the
      civilian population flexible flatfeet are not a source of disability. This study
      is consistent with previous studies and provides additional evidence against the
      practice of treating flexible flatfeet in children.

PMID- 11822692
TI  - Medial eminence thickness with and without hallux valgus.
AB  - The purpose of this study was to determine if hypertrophy of the medial eminence
      occurs in patients with hallux valgus. Thirty-three patients (50 consecutive
      feet) who underwent surgical correction for hallux valgus were evaluated. They
      had preoperative and postoperative radiographs. The hallux valgus angle,
      intermetatarsal angle and size of the medial eminence were recorded. The same
      measurements were then obtained from the radiographs of 50 randomly selected, age
      matched controls with a hallux valgus angle less than 15 degrees and
      intermetatarsal less than 9 degrees. The average width of the medial eminence was
      4.4 mm in the hallux valgus group and 4.1 mm in the control group. In most
      patients, hypertrophy of the medial eminence is not a component of the pathology.

PMID- 11822693
TI  - The accessory flexor digitorum longus as a cause of Flexor Hallucis Syndrome.
AB  - The Flexor Hallucis Syndrome has been associated with ballet and sports
      activities. It has been thought to represent over use with attendant
      tenosynovitis of the tendon in the fibro-osseous tunnel extending from the ankle
      to the midfoot. We report a patient with an accessory flexor digitorum longus who
      presented with classical clinical features of the syndrome. The patient's
      disabling symptoms persisted despite a year and a half of nonoperative treatment.
      They were finally relieved when the accessory muscle was excised. In addition to
      the previously described clinical features of the Flexor Hallucis Syndrome, the
      physical exam included abnormal fullness between the Achilles tendon and the
      tibia. When the ankle was held in dorsiflexion, there was limited dorsiflexion of
      the lateral toes, which were tethered by the "cork-in-a-bottle" effect of the
      distal muscle mass of the accessory flexor digitorum longus muscle at the flexor
      retinaculum and fibro-osseous canal of the flexor hallucis longus. The MRI
      examination confirmed the presence of an abnormal muscle mass extending distal to
      the ankle joint with the foot in neutral. The study also demonstrated fluid in
      the ankle joint and fibro-osseous canal of the flexor hallucis, and marrow edema
      within the body of the talus consistent with chronic inflammation. Follow-up MRI
      six months after excision of the muscle revealed some scar formation at the site
      of the previously excised muscle and complete resolution of the joint effusion,
      fluid in the tunnel of the flexor hallucis, and marrow edema.

PMID- 11822694
TI  - Imaging of frostbite injury by technetium-99m-sestamibi scintigraphy: a case
      report.
AB  - The appearance of superficial tissue is often an unreliable indicator of deep
      tissue viability in cases of frostbite. We present a 34-year-old black man who
      was brought to the emergency department at fourth post-injury day with frostbite
      injury involving both lower extremities after prolonged exposure to subzero
      temperatures. In our previous experimental study, 99mTc sestamibi scintigraphy
      has been employed for evaluating frostbite injuries in rabbit hindlegs. In the
      case presented, 99mTc sestamibi scintigraphy, as a new diagnostic tool, was
      performed for detection of skeletal muscle perfusion on the fourth post-injury
      day. The scintigraphic images show diffusely reduced uptake in soft tissues of
      both calves and feet. It was thought that this hypoperfusion was due to viable
      but ischemic tissue. Five days after medical therapy, 99mTc sestamibi scan showed
      prominently increased uptake in both calves and feet and skin necrosis was
      observed. Debridement of necrotic skin and subcutaneous tissue was performed, and
      split-thickness skin graft was applied for coverage of the skin defect. Healing
      was good 15 days after grafting. We think 99mTc sestamibi scan can be used for
      assessment of soft-tissue perfusion and evaluation of treatment in frostbite
      injury.

PMID- 11822695
TI  - Bilateral calcaneal intraosseous lipoma: a case report.
AB  - Intraosseous lipoma is a rare benign primary lesion of bone. Approximately 180
      cases have been reported to date. In the literature, we have been able to find
      only three patients with bilateral calcaneal involvement. We present a 34-year
      old woman who was diagnosed with intraosseous lipoma in both calcanei.

PMID- 11822696
TI  - Measurement of the first/second intermetatarsal angle following proximal oblique
      metatarsal osteotomy.
AB  - The radiographs of 21 consecutive patients who had undergone proximal oblique
      metatarsal osteotomy were reviewed. The first/second intermetatarsal and MP
      angles were measured before and after surgery using two different well-described
      methods. Values for each patient using the Hardy and Clapham and center-of-head
      methods were compared using a paired t-test. The degrees of angular correction
      obtained for the first/second intermetatarsal angle and MP joint were
      significantly different on the same foot as measured by the two different
      methods. Although we cannot choose between these two methods on the basis of this
      study, we hope to call attention to the discrepancy and urge readers to be
      cautious in comparing the results of studies until consensus may be reached
      regarding standard measurement of radiographic results.

PMID- 11822697
TI  - Angular measurements in the evaluation of hallux valgus deformities: a report of
      the ad hoc committee of the American Orthopaedic Foot & Ankle Society on angular
      measurements.

PMID- 11822698
TI  - Shprintzen-Goldberg marfanoid syndrome: a case followed up for 24 years.
AB  - A patient with Shprintzen-Goldberg syndrome was followed up for 24 years. The
      patient's parents were unrelated and unaffected. Walking and speech were delayed.
      Facial dysmorphism was obvious as well as pectus excavatum, scoliosis, bilateral
      dislocation of the radial heads, hammer toes and hallux valgus, pes planus,
      arachnodactyly, and camptodactyly. Skin was thin and fragile. CT scan showed
      ventricular enlargement. He had a mitral valve prolapse. He was operated on twice
      for bilateral inguinal and crural hernia and several times for his foot
      deformities. Puberty was delayed until 18 years. At 24 years of age he was still
      thin, dolichocephalic, and the facial dysmorphic features were still obvious.
      Pectus excavatum was still severe but the thoracolumbar scoliosis was mild. His
      foot deformities had improved and his joints were less hypermobile. Psychomotor
      development was quite normal. His main concern was the minimal subcutaneous fat
      and fragility of skin. Echocardiography was now normal.

PMID- 11822699
TI  - X-linked inheritance of Dandy-Walker variant.
AB  - We report a family in which two sisters had three male fetuses with isolated
      Dandy-Walker variant (DWV) diagnosed on antenatal ultrasound. DWV is one part of
      a spectrum of abnormalities related to Dandy-Walker malformation (DWM) which
      commonly occur in association with other anomalies with or without chromosome
      abnormalities. The majority of cases are sporadic but rare reports of recurrence
      in siblings exist. This is the second report suggesting that isolated DWM/DWV can
      be inherited as an X-linked recessive trait.

PMID- 11822700
TI  - Optic nerve coloboma, Dandy-Walker malformation, microglossia, tongue
      hamartomata, cleft palate and apneic spells: an existing oral-facial-digital
      syndrome or a new variant?
AB  - We report on a female infant with postaxial polydactyly of the hands, preaxial
      polydactyly of the right foot, cleft palate, microglossia and tongue hamartomata
      consistent with an oral-facial-digital syndrome (OFDS). The patient also had
      optic nerve colobomata, a Dandy-Walker malformation, micrognathia and apneic
      spells. This combination of clinical features has not been previously reported.
      This patient either expands the clinical features of one of the existing OFDS or
      represents a new variant. A review of the literature highlights the difficulties
      in making a specific diagnosis because of the different classification systems
      that exist in the literature.

PMID- 11822701
TI  - Double vagina with sex reversal, congenital diaphragmatic hernia, pulmonary and
      cardiac malformations--another case of Meacham syndrome.
AB  - We report a female infant of 42 weeks gestation with a left sided diaphragmatic
      hernia and a hypoplastic left heart. A true double vagina, absent uterus and
      abnormal male gonads were found in the presence of normal external female
      genitalia. Conventional G band karyotyping of skin samples revealed a normal male
      karyotype. The aetiology and inheritance are unknown. We believe this to be the
      fifth reported case of a recognizable syndrome first reported by Meacham [(1991).
      Am J Med Genet 41:478-481].

PMID- 11822702
TI  - Penile agenesis and clavicular anomaly in a child with an oral facial digital
      syndrome.
AB  - We report a male patient with the clinical characteristics of an OFDS (oral
      facial digital syndrome). He also has penile agenesis, clavicular flattening and
      cerebellar anomalies. This patient was classified as a severe form of OFD type II
      Mohr syndrome but the possibility of this being OFDS VI-Varadi syndrome or a new
      form of OFDS cannot completely be excluded.

PMID- 11822703
TI  - An autosomal recessive syndrome of nasal anomalies associated with renal and
      anorectal malformations.
AB  - We report a consanguineous Arab family with four children affected with bifid
      nose associated with renal agenesis and variable degree of anorectal
      malformations. We suggest that the combination of abnormalities in these children
      represent a previously undescribed autosomal recessive syndrome.

PMID- 11822704
TI  - Neuroblastoma in a dysmorphic girl with a partial duplication of 2p caused by an
      unbalanced translocation.
AB  - A 1-year-old female child with multiple dysmorphic features including
      microcephaly, hypertelorism, a short philtrum, low set ears, a narrow high arched
      palate, micrognathia and growth retardation was found to have a de novo
      chromosome abnormality including a partial duplication of the short arm of
      chromosome 2 and a partial deletion of the long arm of chromosome 17. The
      clinical features of the case shared many similarities to previous reports of
      trisomy 2p. Three years later, ecchymotic spots appeared around the left ocular
      region. Further clinical and pathological examination confirmed the diagnosis of
      a neuroblastoma. This is the first case of an unbalanced translocation, 46, XX,
      der (17), t (2; 17) (p23; q25), showing the development of a neuroblastoma in
      addition to the dysmorphic features. We suggest that trisomy 2p including the N
      myc proto-oncogene may have predisposed the patient to the development of a
      neuroblastoma.

PMID- 11822705
TI  - Monosomy 1p36--a recently delineated, clinically recognizable syndrome.
AB  - Monosomy 1p36 is a recently delineated contiguous gene syndrome, which is now
      considered to be one of the most common subtelomeric microdeletion syndromes. We
      report four unrelated patients with subtle deletions within 1p36 confirmed by
      high resolution karyotyping and FISH. All exhibited severe psychomotor
      retardation. Microcephaly, seizures, and visual impairment occurred in three
      subjects. Results of a first routine karyotyping were unrevealing in three
      probands. The diagnosis was primarily suggested on the basis of a distinct
      pattern of facial anomalies in all except the first case. This report illustrates
      that monosomy 1p36 may be recognized clinically, at least in some patients,
      whereas the diagnosis is easily missed on routine karyotype.

PMID- 11822706
TI  - Sponastrime dysplasia with abnormal urinary glycosaminoglycans and growth hormone
      unresponsiveness.
AB  - Sponastrime dysplasia is a rare skeletal dysplasia characterized by severe short
      stature, scoliosis, a saddle nose, frontal bossing, and increased upper/lower
      segment ratio. Etiology of this condition is unknown. Radiological findings
      include a concavity in the posterior two thirds of lumbar vertebral bodies,
      platyspondyly, thoracolumbar scoliosis, marginal irregularity and striations of
      metaphyses, and delayed bone age. We report a patient with findings of
      sponastrime dysplasia and evaluation of urinary glycosaminoglycans with the
      presence of dermatan sulfate, heparan sulfate, chondroitin 4 sulfate, and
      chondroitin 6 sulfate. This suggests the etiology of this disorder may be
      abnormal cartilage metabolism.

PMID- 11822707
TI  - Osteocraniostenosis in a fetus with a 46,XX/46,XY karyotype.
AB  - Osteocraniostenosis is a disorder characterized by thin tubular bones, dymorphic
      facies and splenic hypoplasia/aplasia in some cases. We report a further case of
      this rare skeletal dysplasia in a 31 week male fetus with ambiguous external
      genitalia and asymmetry in whom a 46,XX/46,XY karyotype was demonstrated in both
      cartilage and skin.

PMID- 11822708
TI  - Lethal acrofacial dysostosis, pre- and post-axial defects of the hands, and
      bilateral renal agenesis.
AB  - We report a female fetus with a previously undescribed form of mandibulofacial
      dysostosis with mesomelic limb abnormalities, pre- and post-axial defects of the
      hands, bilateral renal agenesis, bicornuate uterus, and a single umbilical
      artery.

PMID- 11822709
TI  - Possible new syndrome of microcephaly with cortical migration defects, Peters
      anomaly and multiple intestinal atresias: a multiple vascular disruption
      syndrome.
AB  - A possible new multiple vascular disruption symdrome is described. The male
      patient had microcephaly with cortical migration defects, Peters anomaly and
      multiple inestinal atresias.

PMID- 11822710
TI  - Kabuki syndrome and growth hormone deficiency: description of a case treated by
      long-term hormone replacement.

PMID- 11822711
TI  - Morbid obesity and hyperphagia in the WAGR syndrome.
AB  - A 33-year-old man with WAGR syndrome is described with morbid obesity associated
      with hyperphagia and an apparent lack of satiety. It is possible that a gene
      associated with satiety is present at 11p13 although it is premature to conclude
      that obesity is a specific feature of WAGR syndrome.

PMID- 11822712
TI  - Mild Noonan phenotype associated with coloboma of the iris and choroid.
AB  - A 20-year-old Caucasian male with mild Noonan phenotype associated with coloboma
      of the iris and choroid is described. It is concluded that iris and retinal
      colobomas could be a rare feature of Noonan sydrome.

PMID- 11822713
TI  - Soil carbon dynamics in cropland and rangeland.
AB  - Most soils in the Midwestern USA have lost 30 to 50% of their original pool, or
      25 to 40 Mg C/ha, upon conversion from natural to agricultural ecosystems. About
      60 to 70% of the C thus depleted can be resequestered through adoption of
      recommended soil and crop management practices. These practices include
      conversion from plow till to no till, frequent use of winter cover crops in the
      rotation cycle, elimination of summer fallow, integrated nutrient management
      along with liberal use of biosolids and biological nitrogen fixation, precision
      farming to minimize losses and enhance fertilizer use efficiency, and use of
      improved varieties with ability to produce large root biomass with high content
      of lignin and suberin. The gross rate of soil organic carbon (SOC) sequestration
      ranges from 500 to 800 kg/ha/year in cold and humid regions and 100 to 300
      kg/ha/year in dry and warm regions. The rate of SOC sequestration can be measured
      with procedures that are cost effective and credible at soil pedon level,
      landscape level, regional or national scale. In addition to SOC, there is also a
      large potential to sequester soil inorganic carbon (SIC) in arid and semi-arid
      regions. Soil C sequestration has numerous ancillary benefits. It is truly a win
      win situation: extremely cost-effective, and a bridge to the future until
      alternative energy options take effect.

PMID- 11822714
TI  - Measuring carbon in forests: current status and future challenges.
AB  - To accurately and precisely measure the carbon in forests is gaining global
      attention as countries seek to comply with agreements under the UN Framework
      Convention on Climate Change. Established methods for measuring carbon in forests
      exist, and are best based on permanent sample plots laid out in a statistically
      sound design. Measurements on trees in these plots can be readily converted to
      aboveground biomass using either biomass expansion factors or allometric
      regression equations. A compilation of existing root biomass data for upland
      forests of the world generated a significant regression equation that can be used
      to predict root biomass based on aboveground biomass only. Methods for measuring
      coarse dead wood have been tested in many forest types, but the methods could be
      improved if a non-destructive tool for measuring the density of dead wood was
      developed. Future measurements of carbon storage in forests may rely more on
      remote sensing data, and new remote data collection technologies are in
      development.

PMID- 11822715
TI  - Methodology for estimating soil carbon for the forest carbon budget model of the
      United States, 2001.
AB  - The largest carbon (C) pool in United States forests is the soil C pool. We
      present methodology and soil C pool estimates used in the FORCARB model, which
      estimates and projects forest carbon budgets for the United States. The
      methodology balances knowledge, uncertainties, and ease of use. The estimates are
      calculated using the USDA Natural Resources Conservation Service STATSGO
      database, with soil dynamics following assumptions based on results of site
      specific studies, and area estimates from the USDA Forest Service. Forest
      Inventory and Analysis data and national-level land cover data sets. Harvesting
      is assumed to have no effect on soil C. Land use change and forest type
      transitions affect soil C. We apply the methodology to the southeastern region of
      the United States as a case study.

PMID- 11822716
TI  - Carbon storage and sequestration by urban trees in the USA.
AB  - Based on field data from 10 USA cities and national urban tree cover data, it is
      estimated that urban trees in the coterminous USA currently store 700 million
      tonnes of carbon ($14,300 million value) with a gross carbon sequestration rate
      of 22.8 million tC/yr ($460 million/year). Carbon storage within cities ranges
      from 1.2 million tC in New York, NY, to 19,300 tC in Jersey City, NJ. Regions
      with the greatest proportion of urban land are the Northeast (8.5%) and the
      southeast (7.1%). Urban forests in the north central, northeast, south central
      and southeast regions of the USA store and sequester the most carbon, with
      average carbon storage per hectare greatest in southeast, north central,
      northeast and Pacific northwest regions, respectively. The national average urban
      forest carbon storage density is 25.1 tC/ha, compared with 53.5 tC/ha in forest
      stands. These data can be used to help assess the actual and potential role of
      urban forests in reducing atmospheric carbon dioxide, a dominant greenhouse gas.

PMID- 11822717
TI  - Soil carbon dynamics and potential carbon sequestration by rangelands.
AB  - The USA has about 336 Mha of grazing lands of which rangelands account for 48%.
      Changes in rangeland soil C can occur in response to a wide range of management
      and environmental factors. Grazing, fire, and fertilization have been shown to
      affect soil C storage in rangelands, as has converting marginal croplands into
      grasslands. Carbon losses due to soil erosion can influence soil C storage on
      rangelands both by reducing soil productivity in source areas and potentially
      increasing it in depositional areas, and by redistributing the C to areas where
      soil organic matter mineralization rates are different. Proper grazing management
      has been estimated to increase soil C storage on US rangelands from 0.1 to 0.3 Mg
      C ha(-1)year(-1) and new grasslands have been shown to store as much as 0.6 Mg C
      ha(-1)year(-1). Grazing lands are estimated to contain 10-30% of the world's soil
      organic carbon. Given the size of the C pool in grazing lands we need to better
      understand the current and potential effects of management on soil C storage.

PMID- 11822718
TI  - Carbon dioxide fluxes over a grazed prairie and seeded pasture in the Northern
      Great Plains.
AB  - Temperate grasslands are vast terrestrial ecosystems that may be an important
      component of the global carbon (C) cycle; however, annual C flux data for these
      grasslands are limited. The Bowen ratio/energy balance (BREB) technique was used
      to measure CO2 fluxes over a grazed mixed-grass prairie and a seeded western
      wheatgrass [Pascopyrum smithii (Rybd) Love] site at Mandan, ND from 24 April to
      26 October in 1996, 1997, and 1998. Above-ground biomass and leaf area index
      (LAI) were measured about every 21 days throughout the season. Root biomass and
      soil organic C and N content were determined to 110 cm depth in selected
      increments about mid-July each year. Peak above-ground biomass and LAI coincided
      with peak fluxes and occurred between mid-July to early August. Biomass averaged
      1227 and 1726 kg ha(-1) and LAI 0.44 and 0.59, for prairie and western
      wheatgrass, respectively. Average CO2 flux for the growing season was 279 g CO2
      m(-2) for prairie and 218 g CO2 m(-2) for western wheatgrass (positive flux is
      CO2 uptake and negative flux is CO2 loss to the atmosphere). Using prior measured
      dormant season CO2 fluxes from the prairie sites gave annual flux estimates that
      ranged from -131 to 128 g CO2 m(-2) for western wheatgrass and from -70 to 189 g
      CO2 m(-2) for the prairie. This wide range in calculated annual fluxes suggests
      that additional research is required concerning dormant season flux measurements
      to obtain accurate estimates of annual CO2 fluxes. These results suggest Northern
      Great Plains mixed-grass prairie grasslands can either be a sink or a source for
      atmospheric CO2 or near equilibrium, depending on the magnitude of the dormant
      season flux.

PMID- 11822719
TI  - Tillage, crop rotation, and organic amendment effect on changes in soil organic
      matter.
AB  - Carbon sequestration in agricultural soils is controlled by the balance of added
      organic residues and microbial oxidation of both residues and native organic
      matter (OM) as moderated by management and tillage. The PC-based model CQESTR
      predicts decomposition of residues, organic amendments and soil OM, based on
      cropping practices. CQESTR uses RUSLE (Revised Universal Soil Loss Equation) crop
      rotation and management practice, crop production, and operation databases. These
      data are supplemented with residue nitrogen and soil OM, bulk density, and layer
      thickness. CQESTR was calibrated with soil carbon data from 70-year-long
      experiments at the Research Center at Pendleton, OR. The calibrated model
      provides estimates with a 95% confidence interval of 0.33% OM. Validation at 11
      independent sites resulted in a matching of observed with calculated OM with a
      95% confidence interval of 0.55% OM. A 12th site, with a history of severe
      erosion, provided a poor match.

PMID- 11822720
TI  - Sensitivity of carbon sequestration costs to soil carbon rates.
AB  - Modifying current agricultural management practices as a means of sequestering
      carbon has been shown to be a relatively low cost way to offset greenhouse gas
      emissions. In this paper we examine the sensitivity of the estimates of the
      amount of soil carbon sequestered and the implied costs of sequestering a tonne
      of carbon to changes in the rates of soil carbon sequestered for alternative
      production practices. An application is made to the dryland grain production
      systems of the US Northern Plains where the marginal costs of soil C range from
      $20 to $100 per MT. We show that the resulting changes in the marginal costs
      quantities of C sequestered are not a monotonic transformation of the changes in
      the soil carbon rates. These results underscore the importance of using a linked
      economic and biophysical simulation model to assess the economic potential for
      sequestering carbon in agricultural soils.

PMID- 11822722
TI  - National-scale estimation of changes in soil carbon stocks on agricultural lands.
AB  - Average annual net change in soil carbon stocks under past and current management
      is needed as part of national reporting of greenhouse gas emissions and to
      evaluate the potential for soils as sinks to mitigate increasing atmospheric CO2.
      We estimated net soil C stock changes for US agricultural soils during the period
      from 1982 to 1997 using the IPCC (Intergovernmental Panel on Climate Change)
      method for greenhouse gas inventories. Land use data from the NRI (National
      Resources Inventory; USDA-NRCS) were used as input along with ancillary data sets
      on climate, soils, and agricultural management. Our results show that, overall,
      changes in land use and agricultural management have resulted in a net gain of
      21.2 MMT C year(-1) in US agricultural soils during this period. Cropped lands
      account for 15.1 MMT C year(-1), while grazing land soil C increased 6.1 MMT C
      year(-1). The land use and management changes that have contributed the most to
      increasing soil C during this period are (1) adoption of conservation tillage
      practices on cropland, (2) enrollment of cropland in the Conservation Reserve
      Program, and (3) cropping intensification that has resulted in reduced use of
      bare fallow.

PMID- 11822721
TI  - Impact of soil movement on carbon sequestration in agricultural ecosystems.
AB  - Recent modeling studies indicate that soil erosion and terrestrial sedimentation
      may establish ecosystem disequilibria that promote carbon (C) sequestration
      within the biosphere. Movement of upland eroded soil into wetland systems with
      high net primary productivity may represent the greatest increase in storage
      capacity potential for C sequestration. The capacity of wetland systems to
      capture sediments and build up areas of deposition has been documented as well as
      the ability of these ecosystems to store substantial amounts of C. The purpose of
      our work was to assess rates of sediment deposition and C storage in a wetland
      site adjacent to a small first-order stream that drains an agricultural area. The
      soils of the wetland site consist of a histosol buried by sediments from the
      agricultural area. Samples of deposited sediments in the riparian zone were
      collected in 5 cm increments and the concentration of 137Cs was used to determine
      the 1964 and 1954 deposition layers. Agricultural activity in the watershed has
      caused increased sediment deposition to the wetland. The recent upland sediment
      is highly enriched in organic matter indicating that large amounts of organic C
      have been sequestered within this zone of sediment deposition. Rates of
      sequestration are much higher than rates that have occurred over the pre-modern
      history of the wetland. These data indicate the increased sedimentation rates in
      the wetland ecosystem are associated with increased C sequestration rates.

PMID- 11822724
TI  - Spatial heterogeneity of aggregate stability and soil carbon in semi-arid
      rangeland.
AB  - To measure and manage for C sequestration in heterogeneous rangeland systems, we
      need to more fully understand spatial patterns of soil resources. Spatial
      distributions of aggregate stability and soil carbon were investigated in a
      semiarid rangeland in New Mexico, USA. Soil was analyzed from plant interspaces,
      black grama (Bouteloua eriopoda (Torr.) Torr.), and mesquite (Prosopis glandulosa
      Torr.) in a landscape-replicated study. Aggregate stability at the 250 microm
      scale, carbonate C, organic C and N, C:N ratio, and glomalin, were all highest
      under mesquite. Soil C:N ratio was the best predictor of aggregate stability.
      Estimates of metric tons of C per hectare in the top 10 cm were highly variable
      at patch and landscape scales, varying from 4.2 to 10.5 under mesquite and from
      3.0 to 7.0 in interspaces. High variability of aggregate stability and soil C has
      important implications for C sequestration. We argue that this multi-scale soil
      heterogeneity must be considered when measuring and managing for C sequestration.

PMID- 11822723
TI  - Net carbon flux from agricultural ecosystems: methodology for full carbon cycle
      analyses.
AB  - Agricultural ecosystems have the potential to sequester carbon in soils by
      altering agricultural management practices (i.e. tillage practice, cover crops,
      and crop rotation) and using agricultural inputs (i.e. fertilizers and
      irrigation) more efficiently. Changes in agricultural practices can also cause
      changes in CO2 emissions associated with these practices. In order to account for
      changes in net CO2 emissions, and thereby estimate the overall impact of carbon
      sequestration initiatives on the atmospheric CO2 pool, we use a methodology for
      full carbon cycle analysis of agricultural ecosystems. The analysis accounts for
      changes in carbon sequestration and emission rates with time, and results in
      values representing a change in net carbon flux. Comparison among values of net
      carbon flux for two or more systems, using the initial system as a baseline
      value, results in a value for relative net carbon flux. Some results from using
      the full carbon cycle methodology, along with US national average values for
      agricultural inputs, indicate that the net carbon flux averaged over all crops
      following conversion from conventional tillage to no-till is -189 kg C ha(-1)
      year(-1) (a negative value indicates net transfer of carbon from the atmosphere).
      The relative net carbon flux, using conventional tillage as the baseline, is -371
      kg C ha(-1) year(-1), which represents the total atmospheric CO2 reduction caused
      by changing tillage practices. The methodology used here illustrates the
      importance of (1) delineating system boundaries, (2) including CO2 emissions
      associated with sequestration initiatives in the accounting process, and (3)
      comparing the new management practices associated with sequestration initiatives
      with the original management practices to obtain the true impact of sequestration
      projects on the atmospheric CO2 pool.

PMID- 11822725
TI  - Influence of livestock grazing on C sequestration in semi-arid mixed-grass and
      short-grass rangelands.
AB  - We evaluated the effects of livestock grazing on C content of the plant-soil
      system (to 60 cm) of two semi-arid grasslands: a mixed-grass prairie (grazed 12
      years), and a short-grass steppe (grazed 56 years). Grazing treatments included
      season-long grazing at heavy and light stocking rates, and non-grazed exclosures.
      Significantly higher soil C (0-30cm) was measured in grazed pastures compared to
      non-grazed exclosures, although for the short-grass steppe higher soil C was
      observed with the heavy grazing treatment only. Excluding grazing caused an
      immobilization of C in excessive aboveground plant litter, and an increase in
      annual forbs and grasses which lack dense fibrous rooting systems conducive to
      soil organic matter formation and accumulation. Our data indicate that higher
      soil C with grazing was in part the result of more rapid annual shoot turnover,
      and redistribution of C within the plant-soil system as a result of changes in
      plant species composition.

PMID- 11822726
TI  - Development of a protocol for evaluation of mammographic surveillance services in
      women under 50 with a family history of breast cancer.
AB  - BACKGROUND: Preliminary retrospective data suggest it is possible to identify
      impalpable breast cancer in women presenting with a family history of breast
      cancer under the age of 50, by using regular mammography. In consequence, this
      service is offered in a number of centres in the UK. The effectiveness of such a
      service, however, has not been fully evaluated. METHODS: We propose to perform
      such an evaluation in a cohort of 20000 women under the age of 50 with a
      significant family history of breast cancer, given regular mammographic
      surveillance over 5 years. Comparison of surgical and pathological data with
      completed and ongoing population screening trials using analysis techniques of
      varying complexity will be performed to obtain an accurate prediction of future
      breast-cancer mortality reduction. The formal aims are: i) to estimate the
      difference in breast-cancer mortality in women under the age of 50 with a
      significant family history of breast cancer having regular mammography, compared
      with those not being screened; ii) to estimate the cost-effectiveness of regular
      mammography in this group of women, compared with no screening. The increase in
      health service resource use attributable to such a policy will be compared with
      no screening, and costed. Incremental cost-effectiveness ratios of implementing
      the standardised mammography strategy compared with no screening will be
      presented in terms of the additional cost per cancer detected, per life saved and
      per life-year saved.

PMID- 11822727
TI  - Measures of familial aggregation as predictors of breast-cancer risk.
AB  - BACKGROUND: Several measures of familial disease aggregation have been proposed,
      but only a few of these are designed to be implemented at the individual level.
      We evaluate two of them in the context of breast-cancer incidence. METHODS: A
      population-based cohort consisting of 114 429 women born between 1874 and 1931
      and at risk for breast cancer after 1965 was identified by linking the Utah
      Population Data Base and the Utah Cancer Registry. Two competing methods were
      used to obtain predictors of familial aggregation of risk: the number of first
      degree relatives with breast cancer (NIST) and the familial standardised
      incidence ratio (FSIR), which weights the disease status of relatives based on
      their degree of relatedness with the proband. Relative risks were estimated using
      Mantel-Haenszel. Poisson regression and spline regression methods. The age
      dependent hazard function was also estimated. RESULTS: Compared to a baseline
      category containing 91.5% of the subjects, the 0.7% of subjects identified as
      high risk using the FSIR criterion had a relative risk of about 2.8, while those
      identified as high risk using the NIST criterion had a relative risk of 2.0.
      Moderate-risk subjects had a relative risk of about 1.75 using either criterion.
      FSIR was a significant predictor of risk even for those with no affected first
      degree relatives. No decline in the baseline risk was observed at advanced ages.
      CONCLUSIONS: FSIR appears to be a better predictor of breast-cancer risk than
      NIST, particularly for high-risk subjects.

PMID- 11822728
TI  - Validity and completeness of registration of surgically treated malignant
      gynaecological diseases in the Danish National Hospital Registry.
AB  - BACKGROUND: The increasing tendency to acquire data by linkage to registries not
      designed for research has introduced a problem into epidemiological research. The
      data is often crude or possibly incomplete and, in some cases, it has been
      proposed to use these registries in the routine acquisition of data for existing
      epidemiological research registries. This study estimates the validity and
      completeness of the registration of surgically treated malignant gynaecological
      diseases in the Danish National Hospital Registry 1977-88. METHODS: Completeness
      was estimated by the method of independent case ascertainment, by comparison with
      the registration of surgically treated gynaecological cancer cases registered in
      the Danish Cancer Registry. The validity of the diagnoses was analysed by
      comparison with the recoding of discharge summaries describing the admission of a
      5% random sample. RESULTS: The completeness of registration was 87% overall.
      Ovarian cancer, cervical cancer and cancer of the uterus were registered with a
      positive predictive value (PPV) of 89-90%. DISCUSSION: The results of the study
      emphasise the need to consider the validation of Danish Hospital Registry data
      before linkage and analysis. In epidemiological cancer research the Danish Cancer
      Registry is the better alternative when information on malignant tumours is
      needed.

PMID- 11822729
TI  - Repeatability of sexual history in longitudinal studies on HPV infection and
      cervical neoplasia: determinants of reporting error at follow-up interviews.
AB  - BACKGROUND: Misclassification of sexual history due to faulty recall or reporting
      bias may be the reason for variability in the association between sexual history
      and human papillomavirus (HPV) infection seen in studies conducted in different
      geographical areas. This study aimed to assess the repeatability of questionnaire
      information on sexual-history variables and their correlates, using information
      from repeat interviews by six international prospective cohort studies. METHODS:
      The pooled dataset included over 14 775 women interviewed on two separate
      occasions, of whom 5690 returned for a third interview. At each return visit
      women were re-asked questions on age at first intercourse and number of sexual
      partners. The six cohorts originated from studies in Denmark, Costa Rica. San
      Francisco, Toronto, Montreal and Sao Paulo. RESULTS: Exact agreement between age
      at first intercourse recalled on separate occasions ranged from 60-85%, whereas
      exact recall rates for number of sexual partners were substantially lower and
      more study-dependent, varying between 20% and 77%. The intraclass correlation
      coefficients gauging the degree of repeatability in responses ranged from 0.68 to
      0.97 for age at first intercourse and 0.08 to 0.94 for number of sexual partners.
      Age, ethnicity, education and cohort membership were the strongest predictors of
      reporting error for both sexual history markers, although study design
      characteristics also seemed to play a role. HPV infection status seemed to
      influence recall of number of partners, but not age at first intercourse.
      CONCLUSIONS: Information on sexual behaviours is not reliably collected in
      epidemiological studies of sexually transmitted diseases, which may influence the
      magnitude of relative risk estimates.

PMID- 11822730
TI  - Arterial hypertension as a risk factor for chronic symmetric polyneuropathy.
AB  - OBJECTIVE: To assess whether arterial hypertension (AH) is an independent risk
      factor for chronic symmetric polyneuropathy (CSP) in the elderly. BACKGROUND: A
      strong relationship has been detected between AH and distal symmetric
      polyneuropathy in insulin-dependent and non-insulin-dependent diabetes. However,
      the correlation between AH and polyneuropathy caused by other clinical conditions
      has not yet been studied. METHODS: Four thousand one hundred and ninety-one
      subjects aged > or = 55 years seen in office consultations by 25 general
      practitioners (GPs) from two separate areas in Italy were interviewed, using a
      pretested semistructured questionnaire covering conditions commonly associated
      with neuropathy and symptoms of peripheral nerve disease. A neurologist later
      visited individuals with > or = 2 symptoms of polyneuropathy and a diagnosis of
      CSP was made in the presence of bilateral, fairly symmetric impairment of at
      least two among strength, sensation and tendon reflexes. AH was ascertained when
      known to the GP and/or if the patient was being treated with antihypertensive
      drugs. RESULTS: One hundred and fifty one subjects had CSP (3.6%). Diabetes was
      the commonest associated condition (18%). AH was present in 47 patients with CSP
      (31%). The odds ratio (OR) of AH in patients with CSP was 4.5 [95% confidence
      interval (CI) 3.1-6.6]. The OR of AH was 3.2 (95% CI 1.5-6.9) in patients with
      diabetes, and 5.7 (95% CI 3.6-9.3) in those without diabetes. The OR of AH was
      4.8 (95% CI 4.4-5.2) after adjusting for the commonest risk factors for CSP.
      CONCLUSION: AH may be an independent risk factor for CSP in the elderly.

PMID- 11822731
TI  - Molecular characterisation and chromosomal mapping of transcripts having tissue
      specific expression in the malaria mosquito Anopheles gambiae: possible
      involvement in visual or olfactory processes.
AB  - We have compared the transcriptional activity of heads, antennae + palps, and
      carcasses in the mosquito Anopheles gambiae by means of differential display PCR
      (DD-PCR). Three transcripts specifically or preferentially expressed in the heads
      and in the antennae + palps have been selected. All are very similar to genes
      related to visual and olfactory mechanisms of several different organisms. They
      have been named Ag arrestin, Ag rLDL, and Ag dynamin. The potential of the DD-PCR
      technique in identifying genes involved in mosquito behaviour and the usefulness
      of the molecular characterisation of these transcripts are discussed.

PMID- 11822732
TI  - Surface charge of Plasmodium falciparum merozoites as revealed by atomic force
      microscopy with surface potential spectroscopy.
AB  - Electric charges on the surface of Plasmodium falciparum merozoites and
      erythrocytes were investigated by atomic force microscopy with surface potential
      spectroscopy. The apical end of merozoites was positively charged, while the
      entire erythrocyte surface was negatively charged. Transmission electron
      microscopy also demonstrated that negatively charged nanogold particles attached
      to the apical end of merozoites, and cationized ferritin particles attached to
      the entire surface of the erythrocyte. This indicates that the surface charge at
      the apical end of the merozoite may play an important role in invasion of the
      erythrocyte.

PMID- 11822733
TI  - Differentiation of Trypanosoma rangeli: high production of infective
      Trypomastigote forms in vitro.
AB  - In the present study, we report a simple method to induce high Trypanosoma
      rangeli differentiation in vitro, producing a large number of infective
      trypomastigote forms. Parasites from SC-58 (Brazil) and Choachi (Colombia)
      strains were cultivated at 27 degrees C in TC-100, Grace and DMEM media, each
      supplemented with 5% fetal bovine serum and prepared at three distinct pHs (6.0,
      7.0, 8.0). Differentiation was microscopically evaluated at 0, 3 and 6 days after
      cultivation in each medium by determining the percentage of trypomastigotes in
      Giemsa-stained smears. Our data revealed similar results for both T. rangeli
      strains, showing (after 6 days of cultivation in DMEM medium, pH 8.0) the
      presence of about 80% of trypomastigotes. These culture-derived trypomastigotes
      proved to be infective to both Balb-C mice and Rhodnius spp, reaching the
      triatomine's salivary glands. Our results describe a new and easy method to
      induce high T. rangeli differentiation in vitro, allowing further studies on the
      antigenic constitution of trypomastigotes.

PMID- 11822734
TI  - Relationship between the efficacy of praziquantel treatment and the cystic
      differentiation in vivo of Echinococcus granulosus metacestode.
AB  - The cyst differentiation of protoscolices inoculated in NMRI mice was studied in
      detail. Although the laminated layer began its formation at 21 days post
      infection (p.i.), we could not identify this structure in all parasites until 34
      days p.i.. At 34 days p.i., all protoscolices were transformed into the
      metacestode stage. Subsequently, the efficacy of praziquantel (PZ) was studied in
      different stages of development of the parasite. We have found a different PZ
      susceptibility in both earlier stages and well-developed cyst. PZ treatment
      exhibited a high efficacy at the beginning of cyst differentiation and a zero
      efficacy in the mature metacestode when the cystic layers were totally developed.
      The relationship between the tegumental ultrastructural changes occurring during
      the vesicular evolution of protoscolices in NMRI mice and the efficacy of PZ
      treatment is discussed in the present study.

PMID- 11822735
TI  - Electron microscopic investigations on stages of dog piroplasms cultured in
      vitro: Asian isolates of Babesia gibsoni and strains of B. canis from France and
      Hungary.
AB  - Stages obtained from two Asian Babesia gibsoni-isolates cultured in vitro were
      studied by means of transmission electron microscopy and compared to strains of
      B. canis cultured in vitro. While the developmental stages of the latter
      preserved their shape in culture, many of the initially small stages of the B.
      gibsoni strains grew considerably and often looked rather similar to B. canis.

PMID- 11822736
TI  - In contrast to dogs, red foxes (Vulpes vulpes) did not shed neospora caninum upon
      feeding of intermediate host tissues.
AB  - To clarify whether red foxes (Vulpes vulpes) can be final hosts of Neospora
      caninum, foxes and dogs were fed in parallel on tissues of a sheep and a goat
      experimentally infected with N. caninum. The faeces of at least two of five dogs
      contained N. caninum oocysts, as determined by bioassay. In the faeces of all six
      foxes fed in parallel, oocysts were detected that were larger in size (length
      12.6 +/- 0.5 microm, width 11.8 +/- 0.4 microm) than the oocysts shed by the
      dogs. Ribosomal RNA sequences and the results of an immunoblot-based bioassay
      provided further evidence that these oocysts were different from N. caninum. A
      titration experiment performed to determine the sensitivity of a bioassay
      utilising gerbils showed that as few as five sporulated N. caninum oocysts could
      be detected by this test. This indicates that, in two feeding experiments, less
      than 3,700 and 200 sporulated N. caninum oocysts, respectively, could have been
      among the Hammondia sp.-like oocysts collected from fox faeces. These results
      suggest that the red fox is either an inappropriate final host for N. caninum or
      not at all a final host for this parasite.

PMID- 11822737
TI  - The suppressive effect of dexamethasone on the proliferation of Plasmodium
      falciparum in squirrel monkeys.
AB  - We investigated the effects of dexamethasone (Dx) on the proliferation of
      Plasmodium falciparum Indochina-I/CDC in squirrel monkeys (Saimiri sciureus
      boliviensis). Three splenectomized squirrel monkeys each received 16 perioral Dx
      doses (three times per week for 36 days), at three different dosages (0.2, 0.5,
      and 2.0 mg/ kg). Each monkey was intravenously inoculated with 7.8 x 10(7) red
      blood cells infected with P. falciparum 1 week after the initiation of Dx
      treatment. Parasite growth was suppressed in DX-treated monkeys in a dose
      dependent manner. To determine whether this suppression of parasite development
      was mediated by host immunity, P. falciparum was cultured in vitro in the
      presence of Dx. The development of P. falciparum was also markedly suppressed in
      vitro by Dx treatment in a dose-dependent manner. These results suggest that Dx
      has a direct suppressive effect on the proliferation of P. falciparum both in
      vivo and in vitro, via a mechanism that is not mediated by an immunological
      reaction of the host.

PMID- 11822738
TI  - Post-translational glutamylation and tyrosination in tubulin of tritrichomonads
      and the diplomonad Giardia intestinalis.
AB  - Glutamylated and tyrosinated tubulin were localized in Giardia intestinalis and
      selected trichomonads of the Tritrichomonadinae subfamily, using specific
      monoclonal antibodies directed at each of the post-translational modifications.
      Analysis was carried out using indirect immunofluorescence microscopy. Although
      trichomonad tubulins remained unlabeled by anti-tyrosine tubulin (TUB-1A2), the
      presence of the glutamylation motif (GT 335) was confirmed and found to differ in
      distribution among tritrichomonads. Tritrichomonas muris was most heavily labeled
      with GT 335, while T. foetus was the least so. Like trichomonads, Giardia was
      unreactive to anti-tyrosine tubulin; however, the GT 335 antibody produced marked
      fluorescence in Giardia trophozoites. This study is the first to report
      immunofluorescent localization of tubulin glutamylation in Giardia and confirms
      previously reported mass spectrometry data.

PMID- 11822739
TI  - Prevalence of levamisole and benzimidazole resistance in oesophagostomum
      populations of pig-breeding farms in North Rhine-Westphalia, Germany.
AB  - The objective of this cross-sectional study was to estimate the prevalence of
      anthelmintic resistance in porcine strongylid populations in northern North Rhine
      Westphalia. A random, weighted sample of 144 pig-breeding farms, stratified by
      organisation and herd size, was selected from a total of 706 farms with at least
      ten sows associated with three breeding organisations. On 61 of all visited
      farms, no or insufficient strongylid eggs were found in the faecal samples.
      Eighty-three farms were surveyed for resistance by a larval development test
      (LDT) using a cut-off concentration of 0.58 microg ml(-1) for levamisole and of
      0.0113 microg ml(-1) for thiabendazole. The results indicated resistance to
      levamisole and benzimidazole in Oesophagostomum spp on one and two farms,
      respectively. Quantitative LDT showed increased LD50 values of levamisole (0.24
      microg ml(-1)) and thiabendazole (0.01-0.015 microg ml(-1)) for these field
      populations when compared with a drug susceptible laboratory strain of O.
      dentatum (0.084 microg ml(-1) levamisole; 0.0093 microg ml(-1) thiabendazole).
      Faecal egg count reduction tests using single standard doses of levamisole and
      flubendazole corroborated the LDT results. Thus, the prevalence of levamisole and
      benzimidazole resistance was estimated to be 2-3.5% in sow herds of northern
      North Rhine-Westphalia. The economic importance of these data is assessed.

PMID- 11822740
TI  - Potential of beta-galactosidase-expressing Toxoplasma gondii for in situ
      localization and observation of rare stages of the parasite life cycle.
AB  - A cyst-forming strain of Toxoplasma gondii was transfected with the Escherichia
      coli LacZ gene and expressed beta-galactosidase constitutively. This strain has
      been used to localize and analyze the early stages of development and
      reactivation of T. gondii in mice. The chromogenic detection of the enzyme allows
      an easy detection of the parasites after light fixation and therefore allows a
      submacroscopic analysis of tissue distribution within the organism. Also, it
      allows further embedding and retrieval of rare stages for electron microscopic
      observation. that detect the presence of the parasite and initiate the response,
      and (2) the early stages of reactivation, when the cysts are supposed to break
      open and release the infectious bradyzoites. We have taken advantage of the
      possibility of detecting the enzymatic activity of beta-galactosidase (beta-gal)
      in transfected parasites to show that one could perform a semi-macroscopic
      detection and that this was compatible with further analysis by histological or
      electron microscopic techniques, being therefore able to detect the rare events
      and then to analyze them further with more refined morphological techniques.

PMID- 11822741
TI  - Fine structure of Sarcocystis singaporensis merogony stages preceding sarcocyst
      formation in the rat.
AB  - The fine structure of merogony stages of Sarcocystis singaporensis (Zaman and
      Colley, 1975) is described from experimentally infected laboratory rats, 10 days
      after being fed sporocysts obtained from naturally infected Python reticulatus
      from Singapore. Infection was shown to consist exclusively of S. singaporensis.
      Parasites developed in the endothelial cells of the lungs, brain, kidney and
      heart. Infection comprised meronts prior to division, dividing and divided
      meronts, and dispersed merozoites. Undivided meronts developed deep pellicular
      invaginations and extensions of the nucleus toward the cell boundary, seemingly
      to sustain metabolic exchange. The course of merogonous development was the same
      in all organs. Hypertrophy of the endothelium induced by invading merozoites
      appeared to lead to obstruction of the capillary lumen.

PMID- 11822742
TI  - The effects of the antiprotozoal drugs metronidazole and furazolidone on
      trophozoites of Giardia lamblia (P1 strain).
AB  - The effects of metronidazole and furazolidone on Giardia lamblia trophozoites
      were analyzed by video-light and transmission electron microscopy. In addition,
      growth curves were drawn based on four concentrations of the drugs. The IC50 was
      4.6 microM for metronidazole and 2.9 microM for furazolidone. By light microscopy
      we observed that metronidazole-treated cells maintained the characteristic body
      shape, but many showed bubbles in the dorsal and ventral surfaces. The effects of
      furazolidone include changes in the morphology (the cells were roundish) and also
      cytoplasmic extrusions. When observed by transmission microscopy, cells treated
      with metronidazole appeared rounder than usual and membranous structures were
      observed in the cytoplasm. Cells treated with furazolidone showed the cytoplasm
      depleted of its contents and great changes in volume. Our results show that
      furazolidone was more effective than metronidazole and its effects were observed
      in cells treated with 1 microg/ml (the lowest concentration) as early as 6 h
      after the start of exposure.

PMID- 11822743
TI  - Effect of exogenous nitric oxide in experimental trichinellosis.
AB  - Nitric oxide (NO) is a free radical that has been given much attention over the
      past few years. It has been nicknamed a "killer" and "mediator" due to its toxic
      and signaling properties. Apart from its regular physiological function, NO
      indirectly participates in infectious diseases. Our investigations showed that NO
      administered as a drug may involve higher histopathological changes in infected
      animals and can involve higher infection. This report seems to be the first
      presentation of the participation of NO reactive nitrogen intermediates in the
      morphological transformation of muscle cells in trichinellosis.

PMID- 11822744
TI  - The importance of a multidisciplinary approach in systematics: another opinion.

PMID- 11822745
TI  - More on the benefits of smoking.

PMID- 11822746
TI  - Pre-operative endocrine therapy for postmenopausal women: when and why?

PMID- 11822747
TI  - Glycemic index, hyperinsulinemia, and breast cancer risk.

PMID- 11822748
TI  - Time to consider HPV testing in cervical screening.

PMID- 11822749
TI  - Polymorphisms of metabolizing enzymes and transporter proteins involved in the
      clearance of anticancer agents.
AB  - BACKGROUND: The efficacies and toxicities of anticancer agents vary greatly among
      patients. This is attributable to the activities of drug-metabolizing enzymes and
      membrane transporters, primarily determined by polymorphisms of the functions of
      genes encoding these proteins. DESIGN: We reviewed the available literature on
      drug-metabolizing enzymes and membrane transporters, especially their
      physiological functions, genetic and functional polymorphisms, and involvement in
      metabolism, pharmacokinetics and toxicity of anticancer agents. RESULTS: Nine
      enzymes metabolizing anticancer agents have been shown to have genetic
      polymorphisms: dihydropyrimidine dehydrogenase, cytochrome P450, NAD(P)H:quinone
      oxidoreductase 1, N-acetyltransferase 2, thiopurine methyltransferase,
      glutathione S-transferase, and uridine diphosphate glucuronosyltransferase.
      Decreased activities of these proteins can cause not only inherited metabolic
      disorders, but also extraordinarily severe toxicity in cancer patients given
      chemothearpy. Transporter proteins mediate cellular uptake and secretion of
      organic anions and cations. These proteins have recently been shown to play
      critical roles in the clearance of anticancer agents, although relations between
      patients' genetics backgrounds and the clinical significance of drug actions are
      poorly understood. CONCLUSIONS: Further studies should be focused on dosing and
      selection of anticancer agents, based on the type and extent of metabolic
      variation among individuals, in order to avoid adverse reactions and therapeutic
      failure.

PMID- 11822750
TI  - Preoperative treatment of postmenopausal breast cancer patients with letrozole: A
      randomized double-blind multicenter study.
AB  - BACKGROUND: A randomized, double-blind, multicenter study was conducted to
      compare the anti-tumor activity of letrozole vs. tamoxifen in postmenopausal
      women with ER and/or PgR positive primary untreated breast cancer. PATIENTS AND
      METHODS: Three hundred thirty-seven postmenopausal women with ER and/or PgR
      positive primary untreated breast cancer were randomly assigned once daily
      treatment with either letrozole 2.5 mg or tamoxifen 20 mg for four months. At
      baseline none of the patients were considered to be candidates for breast
      conserving surgery (BCS) and 14% of the patients were considered inoperable. The
      primary endpoint was to compare overall objective response (CR + PR) determined
      by clinical palpation. Secondary endpoints included overall objective response on
      ultrasound and mammography and the number of patients who qualified for BCS.
      RESULTS: Overall objective response rate (clinical palpation) was statistically
      significantly superior in the letrozole group, 55% compared to tamoxifen, 36% (P
      < 0.001). Secondary endpoints of ultrasound response, 35% vs. 25% (P = 0.042),
      mammographic response, 34% vs. 16% (P < 0.001), and BCS, 45% vs. 35% (P = 0.022)
      between the letrozole and tamoxifen groups, respectively, showed letrozole to be
      significantly superior. Both treatments were well tolerated. CONCLUSIONS: This
      study shows that letrozole is more effective than tamoxifen as preoperative
      therapy in postmenopausal patients with ER and/or PgR positive primary untreated
      breast cancer and is at least as well tolerated.

PMID- 11822751
TI  - Dietary glycemic index and glycemic load, and breast cancer risk: a case-control
      study.
AB  - BACKGROUND: Certain types of carbohydrates increase glucose and insulin levels to
      a greater extent than others. In turn, insulin may raise levels of insulin-like
      growth factors, which may influence breast cancer risk. We analyzed the effect of
      type and amount of carbohydrates on breast cancer risk, using the glycemic index
      and the glycemic load measures in a large case-control study conducted in Italy.
      PATIENTS AND METHODS: Cases were 2,569 women with incident, histologically
      confirmed breast cancer interviewed between 1991 and 1994. Controls were 2588
      women admitted to the same hospital network for a variety of acute, non
      neoplastic conditions. Average daily glycemic index and glycemic load were
      calculated from a validated 78-item food frequency questionnaire. RESULTS: Direct
      associations with breast cancer risk emerged for glycemic index (odds ratio, OR
      for highest vs. lowest quintile = 1.4; P for trend <0.01) and glycemic load (OR =
      1.3; P < 0.01). High glycemic index foods, such as white bread, increased the
      risk of breast cancer (OR = 1.3) while the intake of pasta, a medium glycemic
      index food, seemed to have no influence (OR = 1.0). Findings were consistent
      across different strata of menopausal status, alcohol intake, and physical
      activity level. CONCLUSIONS: This study supports the hypothesis of moderate,
      direct associations between glycemic index or glycemic load and breast cancer
      risk and, consequently, a possible role of hyperinsulinemia/insulin resistance in
      breast cancer development.

PMID- 11822752
TI  - Formestane, a steroidal aromatase inhibitor after failure of non-steroidal
      aromatase inhibitors (anastrozole and letrozole): is a clinical benefit still
      achievable?
AB  - BACKGROUND: There are few clinical data on the sequential use of aromatase
      inhibitors (AI). This paper focuses on the relevance of clinical benefit CB (CR +
      PR + SD > or = 6 months) in postmenopausal metastatic breast cancer (MBC)
      patients treated with the steroidal aromatase inhibitor (SAI) formestane (FOR).
      who had already received non-steroidal aromatase inhibitor (nSAI): letrozole
      (LTZ) or anastrozole (ANZ). PATIENTS AND METHODS: Twenty postmenopausal women
      with MBC were analysed in this retrospective two-centre study with the sequence
      nSAI-FOR. When receiving ANZ, 1 of 11 achieved a complete response and 9 of 11 a
      stable disease > or = 6 months, and receiving LTZ 1 of 9 achieved a partial
      response and 4 of 9 a stable disease > or = 6 months. The analysis of the entire
      population treated with FOR showed an overall CB of 55% (11 of 20) with a median
      duration of 15 months and median time to progression (TTP) of 6 months.
      CONCLUSIONS: Formestane 250 mg once bi-weekly seems to be an attractive
      alternative third-line hormonal therapy for the treatment of patients with MBC,
      previously treated with nSAI.

PMID- 11822753
TI  - Weekly paclitaxel as first-line chemotherapy and trastuzumab in patients with
      advanced breast cancer. A Hellenic Cooperative Oncology Group phase II study.
AB  - AIM: To evaluate the activity and acute toxicity of the combination of weekly
      paclitaxel as first-line chemotherapy and trastuzumab, in patients with HER-2/neu
      overexpressing advanced breast cancer (ABC). BACKGROUND: Weekly paclitaxel has
      been shown to be a well tolerated treatment with considerable activity in
      patients with ABC. Clinical trials with transtuzumab, a humanized anti-p185 HER
      2/neu monoclonal antibody have demonstrated that this agent produces objective
      responses in patients with ABC. PATIENTS AND METHODS: From December 1998 to April
      2000, 34 patients with HER-2/neu overexpressing ABC were treated with weekly
      paclitaxel; given by one-hour infusion at a dose of 90 mg/m2 immediately followed
      by trastuzumab, 4 mg/kg as a loading dose and 2 mg/kg i.v. given over 30 min,
      thereafter weekly for at least 12 weeks. Expression of HER-2/neu was determined
      by immunohistochemical analysis on fixed, paraffin-embedded tissues. Eligible
      patients were required to have > or = 25% stained tumor cells. RESULTS: Thirty
      three patients completed at least 12 weeks of combined treatment. After
      completion of the 12th week of treatment, four patients (12%) achieved complete
      and 17 (50%) partial response. Median duration of response was 11.6 months. More
      frequent side effects included anemia (56%). neutropenia (27%), peripheral
      neuropathy (78%), diarrhea (30%), alopecia (70%), arthralgias/myalgias (62%),
      fatigue (59%) and hypersensitivity reactions (62%). Median time to progression
      was nine months while median survival had not been reached CONCLUSIONS: The
      combination of weekly paclitaxel and trastuzumab is a safe and active regimen for
      patients with HER-2/neu overexpressing ABC. Randomized phase III studies with
      this combination are warranted.

PMID- 11822754
TI  - Drug distribution and pharmacokinetic/pharmacodynamic relationship of paclitaxel
      and gemcitabine in patients with non-small-cell lung cancer.
AB  - BACKGROUND: Gemcitabine and paclitaxel are two of the most active agents in non
      small-cell lung cancer (NSCLC), and pharmacologic investigation of the
      combination regimens including these drugs may offer a valuable opportunity in
      treatment optimization. The present study investigates the pharmacokinetics and
      pharmacodynamics of paclitaxel and gemcitabine in chemotherapy-naive patients
      with advanced NSCLC within a phase I study. PATIENTS AND METHODS: Patients were
      given i.v. paclitaxel 100 mg/m2 by one-hour infusion followed by gemcitabine
      1,500, 1,750 and 2,000 mg/m2 by 30-min administration. Plasma levels of
      paclitaxel, gemcitabine and its metabolite 2',2'-difluorodeoxyuridine (dFdU) were
      determined by high-performance liquid chromatography (HPLC). Concentration-time
      curves were modeled by compartmental and non-compartmental methods and
      pharmacokinetic/pharmacodynamic (PK/PD) relationships were fitted according to a
      sigmoid maximum effect (Emax) model. RESULTS: Paclitaxel pharmacokinetics did not
      change as a result of dosage escalation of gemcitabine from 1,500 to 2,000 mg/m2.
      A nonproportional increase in gemcitabine peak plasma levels (Cmax, from 18.56 +/
      4.94 to 40.85 +/- 14.85 microg/ml) and area under the plasma concentration-time
      curve (AUC, from 9.99 +/- 2.75 to 25.01 +/- 9.87 h x microg/ml) at 1,500 and
      2,000 mg/m, respectively, was observed, suggesting the occurrence of saturation
      kinetics at higher doses. A significant relationship between neutropenia and time
      of paclitaxel plasma levels > or = 0.05 micromol/l was observed, with a predicted
      time of 10.4 h to decrease cell count by 50%. A correlation was also observed
      between percentage reduction of platelet count and gemcitabine Cmax, with a
      predicted effective concentration to induce a 50% decrease of 14.3 microg/ml.
      CONCLUSION: This study demonstrates the lack of interaction between drugs, the
      nonproportional pharmacokinetics of gemcitabine at higher doses and the Emax
      relationship of paclitaxel and gemcitabine with neutrophil and platelet counts,
      respectively. In addition, gemcitabine 1,500 mg/m2 is the recommended dosage in
      combination with paclitaxel 100 mg/m2 for future phase II studies, due to its
      predictable kinetic behaviour and less severe thrombocytopenia than expected.

PMID- 11822755
TI  - Technetium-99m methoxyisobutylisonitrile chest imaging for small-cell lung
      cancer. Relationship to chemotherapy response (six courses of combination of
      cisplatin and etoposide) and p-glycoprotein or multidrug resistance related
      protein expression.
AB  - AIMS: This is a retrospective and adaptive randomization study. The purpose of
      this study was to evaluate the relationship between technetium-99m
      methoxyisobutylisonitrile (Tc-99m MIBI) chest-imaging results, chemotherapy
      response and P-glycoprotein (Pgp) or multidrug resistance related protein (MRP)
      expression in small-cell lung cancer (SCLC). PATIENTS AND METHODS: Before
      chemotherapy, 30 patients (11 females, 19 males, ages: 52-69 years) with SCLC,
      including 14 extensive diseases without localized problems and 16 limited
      diseases in excess of solitary pulmonary nodule, underwent early chest imaging,
      including visual interpretation and quantitative analyses of tumor uptake ratio
      (TUR), 10 minutes after intravenous injection of Tc-99m MIBI. Immunohistochemical
      analyses were performed, using multiple nonconsecutive sections of the biopsy
      specimens, to detect Pgp and MRP expressions. Chemotherapy response was evaluated
      in the third month after completion of treatment by clinical and radiological
      methods. RESULTS: All 15 (100%) of the SCLC patients with complete or partial
      response had positive Tc-99m MIBI chest SPECT results, but negative ones for both
      Pgp and MRP expression. Twelve of the 15 (80%) SCLC patients with no response or
      progressive disease had negative Tc-99m MIBI chest SPECT results and were
      positive for either Pgp or MRP expression (P < 0.05). Negative Tc-99m MIBI chest
      SPECT results predicted complete or partial response. The TUR of patients with
      complete or partial response (1.91 +/- 0.29 with a 95% confidence interval (95%
      CI): 1.75-2.07) was significantly higher than that of patients with no response
      or progressive disease (1.19 +/- 0.28 with a 95% CI: 1.04-1.35). CONCLUSION: Tc
      99m MIBI chest images are a potential tool for understanding Pgp and MRP
      expressions in SCLC and for predicting patient chemotherapy response.

PMID- 11822756
TI  - A phase I study of sequential intravenous topotecan and etoposide in lung cancer
      patients.
AB  - PURPOSE: The topoisomerase I inhibitor topotecan (T) and the topoisomerase II
      inhibitor etoposide (E) are active drugs in lung cancer. The complementary
      functions of their targets may suggest benefit from the combined use of these
      agents but drug scheduling has been shown to play a critical role in preclinical
      models. To establish the optimal schedule and assess the impact of sequential
      administration of the combination of T and E, we conducted a dose finding study
      of sequential intravenous T and E in a four-weekly-schedule in relapsed lung
      cancer patients. PATIENTS AND METHODS: The importance of drug sequence was
      assessed in consecutive patients throughout all dose levels; patients received in
      the first course either T followed by E (the TE group: T on days 1-3 and E on
      days 4-6) or E before T (the ET group: F on days 1-3 and Ton days 4-6). The
      sequence of Tand E was alternated in the successive courses. In this crossover
      design, each patient served as his own control for analysis of hematological
      toxicity in which TE sequence was compared to that of the ET sequence. Moreover,
      hematological toxicity after the first course was compared between the TE and the
      ET groups. The starting dose was T/E 0.75/75 mg/m2 at dose level 1and dose
      escalation was planned to T/E 1.00/75 mg/nm2 at dose level 2, T/E 1.00/100 mg/m2
      at dose level 3, T/E 1.25/100 mg/m2 at dose level 4 and T/E 1.50/100 mg/m2 at
      dose level 5. Nineteen patients (small-cell lung cancer 7, non-small-cell lung
      cancer 11, mesothelioma 1 patient) were included. RESULTS: The principal toxicity
      was myelosuppression, primarily neutropenia and thrombocytopenia. At dose level 3
      several grade 4 toxicities were observed. DLT (febrile neutropenia) occurred in
      two patients, one in the TE and one in the ET group and precluded further dose
      escalation. There was no significant difference in WBC and platelet nadirs during
      the first course between the TE and the ET group. The influence of the sequence
      of administration of topotecan and etoposide was calculated by comparing the
      nadir values of cycles I and II for each patient. For none of the dose levels, a
      significant sequence-dependent effect could be detected. The MTD was reached at
      the doses of 100 mg/m2 topotecan and 75 mg/m2 etoposide. No objective responses
      were seen. CONCLUSION: Although the combined use of topoisomerase I and II
      inhibitors is attractive on theoretical grounds, excessive myelosuppression
      prevents substantial dose escalation.

PMID- 11822757
TI  - A phase II study of irinotecan with 5-fluorouracil and leucovorin in patients
      with previously untreated gastric adenocarcinoma.
AB  - BACKGROUND: A phase II study testing the safety and efficacy of irinotecan (CPT
      11). 5-fluorouracil (5-FU), and leucovorin (LCV) was conducted in patients with
      advanced gastric adenocarcinomas. PATIENTS AND METHODS: Patients with metastatic
      or recurrent adenocarcinoma of the gastroesophageal junction (GEJ) or stomach
      were entered onto this study. Previous chemotherapy for metastatic disease was
      not allowed. Treatment consisted of repeated 6-week cycles comprising CPT-11 125
      mg/m2 intravenously (i.v.) followed immediately by LCV 20 mg/m2 i.v. and 5-FU 500
      mg/m2 i.v., all given weekly for four weeks followed by a two-week rest. RESULTS:
      Thirty-eight patients were enrolled and 36 eligible patients received protocol
      therapy. Grade 3-5 toxicities consisted primarily of neutropenia (36%) and
      diarrhea (28%). Neutropenic infection was observed in 14% of patients, with 3
      (8%) dying of neutropenic sepsis. The overall response rate was 22% (95%
      confidence interval [CI] 8.5% to 35.5%). Median survival was 7.6 months, and
      median time to progression was 4.4 months. CONCLUSION: This weekly regimen of CPT
      11 with bolus 5-FU/LCV is active in patients with advanced adenocarcinomas of the
      stomach or gastroesophageal junction. While rates of grade 3-4 neutropenia and
      diarrhea were similar to those observed historically in patients receiving this
      regimen for colorectal cancer, neutropenic fever/sepsis appeared to be more
      frequent, and dose modifications were substantial. Future trials of this
      combination in patients with gastric cancer should decrease the absolute starting
      drug doses and/ or employ altered scheduling that better accommodates the pattern
      of toxicity.

PMID- 11822758
TI  - N-(phosphonacetyl)-L-aspartate and calcium leucovorin modulation of fluorouracil
      administered by constant rate and circadian pattern of infusion over 72 hours in
      metastatic gastrointestinal adenocarcinoma.
AB  - BACKGROUND: We have reported that N-(phosphonacetyl)-L-aspartic acid (PALA) 1266
      mg/m2 can safely be given 24 hours prior to the start of a 72-hour infusion of
      fluorouracil (FUra) and leucovorin (LV) at doses of 2000 and 500 mg/m2/day. Since
      inhibition of aspartate carbamoyltransferase (ACTase) activity was evident 4
      hours post PALA, we wished to evaluate PALA given 1 hour prior to FUra. Further,
      we studied the toxicity and pharmacokinetics with FUra given by either fixed- or
      variable-rate infusion. PATIENTS AND METHODS: Twenty-seven patients with
      gastrointestinal tract adenocarcinomas were treated with PALA 1266 mg/m2/15 min
      followed by a 72-hour infusion of FUra and LV (1750 & 500 mg/m2/day) given by
      fixed- or variable-rate (peak at 4:00 A.M.). RESULTS: Clinical toxicity was
      similar in two consecutive cycles in 17 patients receiving fixed- and variable
      rate infusion at the same FUra dose. Overall, grade 3 stomatitis and hand-foot
      syndrome occurred in 12% and 4% patients receiving fixed- and in 16% and 10.5% of
      patients receiving variable-rate infusions. Six of 24 evaluable patients (25%)
      had a partial response. The profile of FUra plasma levels (Cp) over a 24-hour
      period during fixed- and variable-rate infusions were strikingly different, but
      the average Cp and area under the concentration-time curves were comparable.
      ACTase activity was significantly decreased at 4 and 24 hours after PALA (12% and
      18% of baseline; P < 0.001), but enzyme activity had recovered to 40% by 72
      hours. CONCLUSIONS: This regimen was active and well tolerated with similar
      toxicities with FUra given by either fixed- or variable rate infusion. PALA 1266
      mg/m2 significantly inhibited ACTase activity for at least 24 hours.

PMID- 11822759
TI  - Micronutrients and ovarian cancer: a case-control study in Italy.
AB  - BACKGROUND: The role of selected micronutrients, vitamins and minerals in the
      aetiology of epithelial ovarian cancer was investigated using data from a case
      control study conducted between 1992 and 1999 in five Italian areas. PATIENTS AND
      METHODS: Cases were 1,031 patients with histologically confirmed incident
      epithelial ovarian cancer. Controls were 2,411 subjects admitted for acute, non
      neoplastic diseases to major hospitals in the same catchment areas. Dietary
      habits were elicited using a validated food frequency questionnaire including 78
      food groups and recipes. Odds ratios (OR) and 95% confidence intervals (95% CI)
      were computed by quintiles of intake of nutrients. RESULTS: Inverse associations
      emerged for vitamin E (OR = 0.6; 95% CI: 0.5-0.8), beta-carotene (OR = 0.8; 95%
      CI: 0.6-1.0), lutein/zeaxanthin (OR = 0.6; 95% CI: 0.5-0.8 for the highest vs.
      the lowest quintile of intake), and calcium intake (OR = 0.7; 95% CI: 0.6-1.0).
      When the combined effect of calcium and vitamin E was considered, the OR reached
      0.4 (95% CI: 0.3-0.7) for subjects in the highest compared to those in the lowest
      intake tertile of both micronutrients. Results were consistent across strata of
      menopausal status, parity and family history of ovarian or breast cancer.
      CONCLUSIONS: The intake of selected micronutrients, which were positively
      correlated to a diet rich in vegetables and fruits, was inversely associated with
      ovarian cancer.

PMID- 11822761
TI  - Computed tomography of pulmonary metastases from osteosarcoma: the less poor
      technique. A study of 51 patients with histological correlation.
AB  - BACKGROUND: The purpose is to evaluate the accuracy of computed tomography (CT)
      in the pulmonary staging of osteosarcoma. PATIENTS AND METHODS: Fifty-one
      patients presenting with osteosarcoma and at initial CT considered metastatic to
      the chest had lung surgery. Two teams of two senior radiologists independently
      reviewed all CT examinations. Their results were compared to the histological
      studies. RESULTS: One hundred nineteen CT's were reviewed. The 2 teams found 247
      and 268 nodules on the initial. and 143 and 146 nodules on the preoperative CT.
      Histological studies confirmed metastatic nodules in 29 patients. Two hundred
      four nodules were excised and studied. One hundred nine were metastases. The 22
      patients without metastases had 53 negative nodules removed. In the 29 patients
      with metastases, 151 nodules were removed, and 42 were non-metastatic. The
      positive predictive value was 53% with regard to 'nodules', and 57% with regard
      to 'patients'. Only 4 out of 13 patients with one nodule at surgery were
      metastatic, but all patients with more than 7 nodules were metastatic. The 46
      cases with several available CT's, showed that no change in the number of nodules
      was more frequent in benign lesions. Other criteria revealed no significant
      difference. CONCLUSION: CT positive predictive value is limited, but as surgery
      is the only way to cure metastatic patients, CT will still be used as the
      reference technique until a more specific approach can be found.

PMID- 11822760
TI  - Result of two randomized trials comparing nolatrexed (Thymitaq) versus
      methotrexate in patients with recurrent head and neck cancer.
AB  - We report on two randomized trials performed in the USA and Europe, which
      compared methotrexate and nolatrexed as treatment for patients with recurrent
      head and neck cancer. Eligibility criteria included: histologically confirmed
      squamous-cell carcinoma, measurable disease, adequate hematological, renal and
      hepatic functions, failure of a first-line chemotherapy, and informed consent.
      Methotrexate 40 mg/m2 was weekly given by short infusion, and nolatrexed 725
      mg/m2 per day was administered as a five-day continuous infusion, every three
      weeks. A total of 139 patients (63 in the USA. 76 in Europe) were randomized
      based on a ratio of 2/1: 93 and 46 received nolatrexed and methotrexate,
      respectively. Patient characteristics included 115 males and 24 females; median
      age 60 years. In the nolatrexed arm, the following grade 3-4 toxicities occurred:
      neutropenia (29.9%) with 3.1% of febrile neutropenia, mucositis (33.3%), and
      vomiting (10.3%). In the MTX arm, the grade 3-4 toxicities were neutropenia
      (7.1%) and mucositis (6.9%). There was no difference in activity between the
      nolatrexed and the methotrexate treatment: 3.3% and 10.8% of objective responses,
      1.9 versus 1.5 months of disease-free progression and 3.5 versus 3.7 months of
      overall survival, respectively. Nolatrexed has demonstrated a similar activity to
      methotrexate.

PMID- 11822762
TI  - Localised disease in cancer of unknown primary (CUP): the value of positron
      emission tomography (PET) for individual therapeutic management.
AB  - BACKGROUND: Two to four percent of cancer patients present with CUP syndrome.
      Median survival for localised disease is 20 and for disseminated disease, seven
      months. For localised disease, curative treatment is more likely and individual
      therapeutic strategies become more important. After conservative diagnostic
      procedures including MRI, the primary is detected in less than 25%. The
      diagnostic value of PET and its influence on therapeutic strategies was
      evaluated. PATIENTS AND METHODS: Forty-two patients with localised CUP were
      investigated from 5 of 98 to 10 of 2000. The presenting site was lymph node
      metastasis in 34 and visceral metastasis in 8 patients. After a median of 7 (3
      11) diagnostic procedures without detection of the primary, but evidence of
      localised disease, PET was performed with fluorine-18-fluorodeoxyglucose.
      RESULTS: In 26 of 42 patients (62%), a primary was suggested by PET and confirmed
      in 18 (43%). In 5 of 18 patients beyond localised disease, additional
      dissemination, not detected by previous diagnostic measures, was diagnosed by
      PET. Overall, dissemination was only detected only by PET in 16 of 42 patients
      (38%). In29 of 42 patients (69%), the PET result influenced selection of the
      definitive treatment. CONCLUSION: In CUP patients, PET has a certain impact on
      detection of the primary as well as of the disseminated disease. and may also
      have a certain impact on therapeutic management.

PMID- 11822763
TI  - Evaluation and appraisal of randomized controlled trials in myeloma.
AB  - PURPOSE: To critically appraise therapeutic innovations tested in randomized
      controlled trials (RCTs) in multiple myeloma from 1966-1998. DESIGN: We performed
      a comprehensive search to identify published RCTs in multiple myeloma. Quality
      dimensions of the design, conduct, analysis and reporting of each trial were
      assessed. RESULTS: We identified 136 RCTs reported in 114 papers. Overall,
      therapeutic efforts in multiple myeloma resulted in a 5% absolute gain in five
      year survival at a cost of a 0.35% increase in treatment related deaths. Hence on
      average a patient enrolled in a RCT in myeloma is 14 (5/35) times more likely to
      be helped than harmed. However, when the RCTs were critically appraised for key
      quality dimensions of trials' conduct, we found that only 7%) of the trials (10
      of 136) were analyzed according to intention-to-treat (ITT), 9% (12 of 136)
      reported a power analysis (beta error), 32% (35 of 111) adequately concealed
      treatment allocation, 78% (106 of 136) provided a detailed description of patient
      withdrawals, and 83%) (19 of 22) of the double blind RCTs had appropriately
      described methodology. CONCLUSIONS: Therapeutic innovations tested through RCTs
      have improved the outcomes of patients with multiple myeloma. However, the
      quality of RCT reporting and methodology in multiple myeloma could be
      substantially improved. Most therapeutic strategies in multiple myeloma are based
      on modest quality, low power evidence. Despite these shortcomings our findings
      suggest patients may often clinically benefit from enrollment in clinical trials
      when available. Patients on average received modest benefit from innovative
      therapies tested in RCTs at little additional risk of side effects.

PMID- 11822764
TI  - Second malignancies after ewing tumor treatment in 690 patients from a
      cooperative German/Austrian/Dutch study.
AB  - BACKGROUND: Ewing tumor treatment involves high cumulative doses of alkylating
      agents and topoisomerase inhibitors, drugs capable of inducing second cancers. We
      analyzed the second cancer risk in a large cohort of consistently treated
      patients. PATIENTS AND METHODS: Six hundred ninety Ewing tumor patients were
      treated between 1992 and 1999 with local therapy and vincristine. doxorubicin,
      ifosfamide and/or cyclophosphamide, and antinomycin D, with or without etoposide
      as a randomized question. Second cancer incidences were estimated by competing
      risk analyses; standardized incidence ratios (SIR) in comparison to registry data
      were compiled. RESULTS: After a median observation time of 56 months (32 months
      for survivors), 6 of 690 patients had developed second cancers: MDS/AML, two,
      ALL/NHL, two, squamous cell carcinoma, one, liposarcoma, one. SIR were increased
      20-30 fold in comparison to the general population. The cumulative second cancer
      risk five years after diagnosis of the Ewing tumor was 0.0093 for the total
      group, zero for patients without etoposide, and 0.0118 with etoposide. Additional
      phase II high-dose therapy increased the risk to 0.0398 after five years.
      CONCLUSIONS: The second cancder risk observed was in the range to be expected in
      cancer survivors. High-dose therapy, and less markedly, etoposide, may contribute
      to the overall second cancer risk.

PMID- 11822765
TI  - Phase I dose-finding and pharmacokinetic trial of irinotecan (CPT-11)
      administered every two weeks.
AB  - OBJECTIVES: This trial was performed to determine the maximum tolerated dose
      (MTD), dose-limiting toxicity (DLT), and pharmacokinetic profile of irinotecan
      (CPT-11) when administered on a once-every-2-week schedule. PATIENTS AND METHODS:
      CPT-11 was administered to successive cohorts of patients at progressively
      increasing starting doses ranging from 125 to 350 mg/m2. The MTD and DLTs were
      determined both for CPT-11 alone and for CPT-11 followed by filgrastim (G-CSF).
      Plasma samples were obtained during the first 24 hours after initial dosing to
      determine the total concentrations (lactone + carboxylate forms) of CPT-11; of
      the active metabolite SN-38; and of SN-38 glucuronide (SN-38G). RESULTS:
      Neutropenic fever was the DLT for CPT-11 at the 300 mg/m2 dose level. When G-CSF
      was added, dose escalation beyond 350 mg/m2 could not be achieved due to grade 2
      3 toxicities that prevented on-time retreatment with CPT-11. Severe, late
      diarrhea was uncommon on this schedule. Peak plasma concentrations of SN-38 and
      SN-38G were approximately 2.5% and 4.2% of the corresponding peak plasma
      concentration for CPT-II, respectively The harmonic mean terminal half-lives for
      CPT-11, SN-38, and SN-38G were 7.1 hours, 13.4 hours, and 12.7 hours,
      respectively. No predictive correlation was observed between CPT-11 or SN-38 peak
      concentration or AUC and first-cycle diarrhea, neutropenia, nausea, or vomiting.
      Across the range of doses studied, mean CPT-11 clearance was 14.0 +/- 4.0 l/h/m2
      and volume of distribution was 146 +/- 45.9 l/m2. CONCLUSIONS: When administered
      every two weeks, the recommended phase II starting dose of CPT-11 is 250 mg/m2
      when given alone and 300 mg/m2 when supported by G-CSF. This every-two-week
      regimen offers a tolerable and active alternative to weekly or every-three-week
      single-agent CPT-11 therapy.

PMID- 11822766
TI  - Oral vinorelbine pharmacokinetics and absolute bioavailability study in patients
      with solid tumors.
AB  - BACKGROUND: Vinorelbine is a vinca alkaloid obtained by hemisynthesis, which
      makes the molecule more lipophilic than the other vincas. An injectable
      formulation is already marketed for the treatment of non small cell lung cancer
      (NSCLC) and advanced breast cancer (ABC). A new oral form has been developed and
      its file registration is being submitted. As part of its development, a clinical
      study was conducted to determine the absolute bioavailability and
      pharmacokinetics of oral vinorelbine administered as softgel capsules, and to
      evaluate its safety profile compared with intravenous administration. PATIENTS
      AND METHODS: Thirty-two patients with solid tumours were included in the study.
      Patients fasted and were randomised to receive vinorelbine on day 1, either as a
      20 minute intravenous (i.v.) infusion of 25 mg/m2 or as softgel capsules at a
      dose of 80 mg/m2. Patients were treated with the alternate route after a one week
      wash-out period. Blood and urine samples for pharmacokinetic analysis were
      collected during each vinorelbine administration. Safety was assessed after each
      administration using the CALGB/expanded CTC classification. RESULTS: Twenty-four
      patients were eligible for pharmacokinetic evaluation. Oral vinorelbine was
      rapidly absorbed at 80 mg/m2 (Tmax 1.4 +/- 0.7 h) and showed a bioavailability of
      43 +/- 14, and close to 40% based on AUC(last) and AUC(inf), respectively. A
      bioequivalence analysis was conducted on dosage-normalised blood exposures.
      Equivalence was demonstrated between 80 mg/m2 oral and 30 mg/m2 i.v., and between
      60 mg/m2 oral and 25 mg/m2 i.v. The inter-individual variability was equivalent
      for both routes (CV: 38% and 39% for oral and i.v., respectively). A correlation
      was found in both methods between AUClast and % nadir variation in white blood
      cells (WBC) and polymorphonuclears (PMN). More cases of neutropenia (all grades
      pooled), leucopenia (grades 3-4 only) and nausea (grades 2-3) were induced by 80
      mg/m2 oral vinorelbine than by 25 mg/m2 i.v. The greatest intensity of these
      effects, following oral administration, probably reflects the higher, observed
      drug exposure. CONCLUSION: At therapeutic dosage levels, pharmacokinetic
      behaviour and safety profiles were similar for both routes. The absolute
      bioavailability of the oral vinorelbine (new, soft gelatine capsule) was close to
      40%. Inter-individual variability in drug exposure was equivalent in both routes.
      The pharmacokinetic/pharmacodynamic (PK/PD) relationship in haematological
      toxicity was independent of the routes of administration. Reliable, corresponding
      doses between oral and i.v. vinorelbine were established, which will result in
      bioequivalent AUC.

PMID- 11822767
TI  - Gemcitabine-induced systemic capillary leak syndrome.
AB  - Systemic capillary leak syndrome (SCLS) is a rare disorder with a high mortality
      rate, characterized by rapidly developing edema, weight gain and hypotension,
      hemoconcentration and hypoproteinemia. This syndrome is caused by sudden,
      reversible capillary hyperpermeability with a rapid extravasation of plasma from
      the intravascular to the interstitial space. Even though SCLS has been suggested
      to be the pathogenic mechanism for the pulmonary toxicity of gemcitabine (GCB), a
      new deoxycytidine analogue with structural similarities to cytosine arabinoside,
      a direct correlation between GCB and SCLS has never been reported. We describe a
      case of repeated SCLS after GCB administration in a 51-year-old male with locally
      advanced non-small-cell lung cancer treated with a combination of cisplatin and
      GCB. The detection of GCB-induced SCLS supports the hypothesis that SCLS could be
      the pathogenic way of GCB pulmonary toxicity. This finding can help to better
      understand and treat the potentially deadly GCB-related acute respiratory
      distress syndrome that is being recognized.

PMID- 11822768
TI  - Staging of breast cancer. Is the evidence so evident?

PMID- 11822769
TI  - Idiosyncratic reaction after oxaliplatin: circumvention by use of a continuous
      infusional administration schedule.

PMID- 11822770
TI  - The role of murMN operon in penicillin resistance and antibiotic tolerance of
      Streptococcus pneumoniae.
AB  - The recently identified murMN operon is essential for the production of branched
      structured muropeptides in the cell wall and also for the expression of the
      resistant phenotype in penicillin-resistant strains of Streptococcus pneumoniae.
      The purpose of studies described in this communication was to understand better
      the role of murMN in penicillin resistance. Deletion of murM in the penicillin
      resistant strain Pen6, which causes reduction in the penicillin MIC from 6.0 to
      0.03 microg/ml, was successfully complemented to recover the original high level
      of penicillin resistance in transformants that received functional murM alleles
      cloned in plasmid pLS578. Inactivation of penicillin resistance was not
      accompanied by any detectable change in the low affinity or abnormal molecular
      size pattern of the penicillin-binding proteins (PBPs) nor in the mosaic sequence
      of PBP2X typical of resistant strain Pen6. Exposure of strain Pen6 with
      inactivated murM to 0.05 microg/ml of penicillin (i.e., a concentration more than
      100 times below the MIC of the parental strain) initiated a phenotypic response
      typical of penicillin-susceptible strains of pneumococci: inhibition of growth
      followed by rapid and extensive loss of viability and lysis. Unexpectedly,
      inactivation of murMN also caused hypersensitivity to lysis by low concentrations
      of a variety of cell wall active antibiotics such as fosfomycin, D-cycloserine,
      and nisin, suggesting that the murMN operon may perform an important regulatory
      role in the control of the irreversible antimicrobial effects of cell wall
      inhibitors.

PMID- 11822771
TI  - Unusual inducible cross resistance to macrolides, lincosamides, and
      streptogramins B by methylase production in clinical isolates of Staphylococcus
      aureus.
AB  - Clinical strains of Staphylococcus aureus UCN7 and UCN8 were inducibly resistant
      to erythromycin, clindamycin, lincomycin, and quinupristin. This unusual
      inducible MLS(B) resistance was due to the presence of an erm(A) or an erm(B)
      gene, which both encode a ribosomal methylase, in S. aureus UCN8 and UCN7,
      respectively. The inducible cross resistance expressed by S. aureus UCN8 was
      associated with an 83-bp deletion in the attenuator of the erm(A) gene that
      removed the second of the two leader peptides and several inverted repeats. The
      presence of an inducible erm(B) gene in S. aureus UCN7 conferred a cross
      resistance MLS(B) phenotype, similar to that usually observed in streptococci.
      Therefore, in S. aureus, besides the classical inducible MLS(B) phenotype
      characterized by inducible resistance to 14- to 15-membered ring macrolides, an
      additional type of inducible cross resistance to macrolides, lincosamides, and
      streptogramins B due to variants of erm(A) or erm(B) genes exist.

PMID- 11822772
TI  - Molecular characteristics of penicillin-binding protein genes of penicillin
      nonsusceptible Streptococcus pneumoniae isolated in the Netherlands.
AB  - Recently, a nation-wide molecular epidemiologic survey of penicillin
      nonsusceptible Streptococcus pneumoniae has been performed in the Netherlands. In
      the current study, we analyzed the genes pbp1a, pbp2b, and pbp2x from these
      clinical isolates at the molecular level, and identified the genetic composition
      of the penicillin-binding domains. The pneumococcal strains were selected on the
      basis of differences in restriction fragment length polymorphism (RFLP) patterns
      of the genes pbp1a, pbp2b, and pbp2x, and represented 8, 7, and 10 distinct
      patterns, respectively. The genetic heterogeneity observed by sequence analysis
      of the pbp gene parts was comparable with the heterogeneity of the entire pbp
      genes as deduced from RFLP analysis. Furthermore, the mutations in the pbp
      sequences of the Dutch isolates invariably matched with the mutations described
      in pbp sequences of penicillin-nonsusceptible pneumococci isolated in other
      countries. Finally, novel mosaic structures were identified indicating horizontal
      exchange of pbp gene parts among penicillin-nonsusceptible pneumococci.

PMID- 11822773
TI  - Antibiotic persistence: the role of spontaneous DNA repair response.
AB  - Persisters are a small proportion of a bacterial population that exists in a
      physiological state permitting survival despite the lethal activity of
      antibiotics. To explain this phenomenon, it has been suggested that persisters
      are bacteria repairing spontaneous errors of DNA synthesis. To verify this
      assumption, Escherichia coli AB1157 and its lexA3 derivative were exposed to a
      dose 6x MIC of various antibiotics representative of different molecular
      mechanisms of action (ampicillin, ceftriaxone, meropenem, amikacin,
      ciprofloxacin). Bacterial cell counts, after 24 hr of exposure to the
      antimicrobials, revealed a reduction of about 90% of viable organisms in the
      lexA3 strains in comparison to the lexA+. In several cases, the number of colony
      forming units decreased below the limit of assay. This behavior was noted with
      all antibiotics used, alone or in combination (amikacin plus ceftriaxone and
      amikacin plus ciprofloxacin). The same experiments were repeated using E. coli
      AB1157 cultured in the presence of mitomycin C (0.25x MIC), and the number of
      survivors exceeded by about 90% the values found in the nonexposed control. In
      contrast, in the sulA background, mitomycin C reacted synergically with all the
      antibiotics tested causing a strong reduction of the survivors in comparison with
      the control. The addition of chloramphenicol (0.125x MIC), on the contrary,
      caused a reduction of the number of survivors of about 90%. These findings
      indicate that, when DNA repair is active (a mechanism known to block cell
      division), the number of survivors is greater than that observed with lexA3.
      Thus, in addition to other possible explanations, persisters might be a fraction
      of bacteria that during antibiotic treatment are not growing because they are
      repairing spontaneous errors of DNA synthesis.

PMID- 11822774
TI  - Persistence of a vancomycin-resistant Enterococcus faecium in an anaerobic
      continuous-flow culture of porcine microflora in the presence of subtherapeutic
      concentrations of vancomycin.
AB  - Recombined porcine continuous-flow culture (RPCF) maintained in a continuous-flow
      fermentation system is effective in protecting neonatal and weaned pigs against
      infection by enteropathogens. In the current study, we demonstrate the effect of
      RPCF on vancomycin-resistant enterococci (VRE) in the presence and absence of
      subtherapeutic levels of vancomycin. Also examined was the ability of VRE to
      transfer vancomycin resistance to endogenous Enterococcus faecalis 137.1. When
      RPCF was challenged with VRE, the rate of VRE clearance was dependent on the
      method of challenge. In the control experiment, RPCF was challenged with 7.0
      log10/CFU/ml VRE. Clearance of VRE from the culture was observed within 7 days at
      a rate of 1.44 log10/day. RPCF containing 0.001 microg/ml vancomycin cleared VRE
      at a slightly lower rate of 0.94 log10/day. RPCF containing 0.01 microg/ml or 0.1
      microg/ml vancomycin reduced the level of VRE from 7.0 log10/CFU/ml to 2.0
      log10/CFU/ml within 9 days, but failed to clear the VRE after 24 days. During the
      period of decline, the VRE clearance rate for the 0.01 microg/ml and 0.1
      microg/ml vancomycin-treated cultures was 0.52 log10/day, and 0.53 log10/day,
      respectively. E. faecalis 137.1 endogenous to RPCF did not acquire the vancomycin
      resistance genes throughout the experiment as evidenced by direct selection,
      ribotyping, and pulsed-field gel electrophoresis.

PMID- 11822775
TI  - The evolution of pandemic clones of methicillin-resistant Staphylococcus aureus:
      identification of two ancestral genetic backgrounds and the associated mec
      elements.
AB  - Previous surveillance studies carried out by our laboratories, primarily in
      Southern and Eastern Europe, Latin America, and the United States, have
      characterized 3,067 methicillin-resistant Staphylococcus aureus (MRSA) hospital
      isolates by a combination of molecular typing methods. Nearly 70% of these
      isolates could be classified into five clonal types showing extensive geographic
      spread. Representative isolates of these clonal types were now reexamined for
      their genetic relatedness by multilocus sequence typing (MLST) and by sequencing
      the polymorphic region of protein A (spaA typing), and also for the type of the
      Staphylococcal Chromosomal Cassette (SCCmec) resident in the bacteria. Three of
      the previously classified clonal types (Iberian, Brazilian, and Hungarian clones)
      shared a common or closely related genetic background A, which was the same as
      the background of the earliest European isolates of MRSA from England and
      Denmark. The Pediatric and New York/Japan clones belonged to a completely
      different genetic background B. The three recently described SCCmec types were
      specifically associated with different pandemic clones: types I and III with
      isolates of genetic background A and type II with isolates of genetic background
      B. A novel SCCmec related to type I, called SCCmec type IV, was identified in
      some MRSA strains belonging to genetic background A as well as B. Structural
      variations in SCCmec types I and III were also observed. The data allow tentative
      identification of an evolutionary pathway for the emergence of pandemic MRSA
      clones and also provide evidence for the multiple, yet restricted, numbers of
      acquisition of the mec element by S. aureus.

PMID- 11822776
TI  - Genetic linkage between resistance to quaternary ammonium compounds and beta
      lactam antibiotics in food-related Staphylococcus spp.
AB  - Little is known about the occurrence of antimicrobial resistance determinants in
      staphylococci isolated from food and food processing industries. Quaternary
      ammonium compound (QAC)-resistant coagulase-negative staphylococci (CNS) isolated
      from food and food-processing industries were investigated for the presence of
      genetic determinants (qacA/B and qacC/smr) encoding resistance to the QAC
      benzalkonium chloride (BC), several antibiotic resistance genes, and
      staphylococcal insertion sequences IS257 and IS256. Six qacA/B-harboring strains
      were resistant to penicillin and hybridized to a blaZ probe. The qacA/B and blaZ
      probes hybridized to plasmids of similar size in three isolates. Molecular and
      genetic characterization of the 23-kb plasmid (pST6) of Staphylococcus
      epidermidis St.6 revealed the presence of qacB adjacent to an incomplete beta
      lactamase transposon Tn552 encoding the gene cluster blaZ, blaR, and blaI.
      Sequence analysis of flanking regions and the intergenic region between blaZ and
      qacB revealed the presence of IS257 downstream of blaZ as well as sin and binR
      between blaZ and qacB. In the three other BC and penicillin-resistant strains,
      the qacA/B and blaZ genes were located on separate plasmids. A qacC harboring S.
      epidermidis strain (St.17) also hybridized to tetK (tetracycline resistance) and
      ermB (erythromycin resistance) genes. The individual genes were located on
      separate plasmids, suggesting no linkage between QAC and antibiotic resistance
      determinants. Plasmid-free Staphylococcus aureus RN4220 allowed uptake of the
      pST6 plasmid DNA, indicating that the resistance genes could potentially be
      transferred to pathogens under selective stress. In conclusion, presence of both
      resistance determinants could lead to co-selection during antimicrobial therapy
      or disinfection in hospitals or in food industries.

PMID- 11822777
TI  - Multicenter surveillance of antimicrobial resistance of major bacterial pathogens
      in intensive care units in 2000 in Taiwan.
AB  - A susceptibility surveillance study of 1,274 bacterial isolates recovered from
      various clinical specimens from patients in intensive care units (ICUs) of five
      major teaching hospitals was carried out from March, 2000, to June, 2000, in
      Taiwan. This study demonstrated a high rate (66%) of oxacillin resistance in
      Staphylococcus aureus (ORSA), a high rate of nonsusceptibility to penicillin
      (intermediate, 50% and highly resistant, 8%), and high rates of cefotaxime
      nonsusceptibility for S. pneumoniae (intermediate, 29% and resistant, 4%),
      Enterobacter cloacae (57%), Serratia marcescens (34%), and Citrobacter freundii
      (60%). High rate of ceftazidime nonsusceptibility for Pseudomonas aeruginosa
      (22%), and high rates of imipenem nonsusceptibility for P. aeruginosa (15%) and
      Acinetobacter baumannii (22%) were also found. The percentage (11.9%) of extended
      spectrum beta-lactamase (ESBL)-producing Escherichia coli was greater than that
      (11.3%) for Klebsiella pneumoniae. Rates of quinupristin-dalfopristin
      nonsusceptibility for S. pneumoniae (42%), Enterococcus faecium (71%), and ORSA
      (39%) were high, but no vancomycin-resistant enterococci were found in this
      study. The resistance rates of some pathogen varied by institution or type of
      ICUs. Surveillance for antimicrobial resistance among bacterial pathogens in
      hospitals, particularly in ICU settings with a preexisting higher resistance
      burden, is mandatory in establishing and/or modifying guidelines for empirical
      treatment of severe infections in ICU patients caused by these antimicrobial
      resistant pathogens.

PMID- 11822778
TI  - Marked differences in antibiotic use and resistance between university hospitals
      in Vilnius, Lithuania, and Huddinge, Sweden.
AB  - Antibiotic use and antimicrobial resistance was compared between Vilnius and
      Huddinge University hospitals. Drug use data were expressed in number of defined
      daily doses/100 bed-days; antimicrobial resistance were given as percentages of
      resistant isolates. Thirty-five and 48 different antibiotic drugs were used in
      Vilnius and Huddinge, respectively. The overall consumption of antibiotics was 15
      DDD/100 bed-days in Vilnius and 43 DDD/100 bed-days in Huddinge.
      Benzylpenicillin, ampicillin, and aminoglycosides were the major antibiotics in
      Vilnius; beta-lactamase-resistant penicillins, cefalosporins, and quinolones in
      Huddinge. In Vilnius, gentamicin made up one-quarter of the use. Staphylococcus
      aureus and Gram-negative isolates from wounds and blood were more resistant to
      gentamicin in Vilnius. S. aureus was more often methicillin resistant in Vilnius
      than in Huddinge. There was no S. aureus-resistant to vancomycin in either
      hospital. The vancomycin-resistant enterococci made up from 4% to 10% in Vilnius
      hospital, but they were not detected in Huddinge hospital (0%). The majority of
      Streptococcus pneumoniae isolates were sensitive to benzylpenicillin in both
      hospitals. The higher resistance of microorganisms to some antibiotics in Vilnius
      may be explained by heavy use of few antibiotics. Lower level of hygiene
      procedures, sampling bias, and other methodological issues may also have
      contributed. Guidelines for antibiotic use and hygienic procedures are now under
      development in Vilnius.

PMID- 11822779
TI  - Antibiotic resistance in Streptococcus pneumoniae in six Latin American
      countries: 1993-1999 surveillance.
AB  - The impact of invasive pneumococcal invasive disease is increased by the
      emergence of antibiotic resistance. We report regional and temporal variations in
      antibiotic resistance for 4,105 invasive Streptococcus pneumoniae isolates
      collected from Latin American children <5 years, between 1993 and 1999. Reduced
      susceptibility to penicillin was detected in 1,182 isolates (28.8%); 36% of these
      were resistant (> or = 2 microg/ml), including 12.6% with MIC > or = 4 microg/ml,
      occurring primarily in serotypes 14 and 23F. Reduced susceptibility to third
      generation cephalosporins was detected in 12.1% of the collection. Mexico had the
      highest proportion of reduced susceptibility to penicillin (51.6%) and to third
      generation cephalosporins (22%), whereas Brazil had the lowest at 20.9% and 0.7%,
      respectively. Isolates cultured from patients with pneumonia were more likely to
      have reduced susceptibility to third-generation cephalosporins than isolates from
      patients with meningitis (p < 0.0001). Susceptibility to trimethoprim
      sulfamethoxazole, chloramphenicol, erythromycin, and vancomycin was tested by
      disk diffusion for 2.899 isolates. Reduced susceptibility was observed for 45.6%,
      11.5%, 6.9%, and 0%, respectively. Thirty-one percent of the strains were
      resistant to > or = 2 drugs. High levels of antibiotic resistance in Latin
      America emphasize the need for the development of and adherence to rational
      antibiotic use guidelines. On-going surveillance will monitor the impact of these
      programs.

PMID- 11822780
TI  - Haemophilus influenzae resistance in Latin America: systematic review of
      surveillance data.
AB  - Haemophilus influenzae is a relevant cause of morbidity and mortality among
      children under 5 years of age in the developing world. In Latin America, H.
      influenzae type b (Hib) conjugate vaccine and surveillance of H. influenzae
      antimicrobial susceptibility have been implemented in recent years. We have
      undertaken a systematic review and a pooled analysis on H. influenzae
      antimicrobial resistance, including reports of 15 Latin America countries over a
      10-year period (1990-2000). We have found that 450 (21.4%) of 2,100 invasive
      isolates were beta-lactamase producers compared to 145 (14.5%) of 998 isolates of
      noninvasive isolates (p < 0.05). Ampicillin resistance was detected among 783
      (21.9%) of 3,577 invasive isolates compared to 111 (17.2%) of 646 noninvasive
      strains (p < 0.05). In contrast, 568 (41.9%) of 1,355 noninvasive strains were
      trimethoprim-sulfamethoxazole (TMP-SMX) resistance against 241 (26.9%) of 897
      invasive ones (p < 0.05). Therefore, TMP-SMX resistance was more common in
      nonsterile fluids than in sterile fluids. Over time, rates of beta-lactamase
      producing strains were stable in Brazil and Mexico, whereas rates of TMP-SMX
      resistance were increasing in Brazil. It is predictable that following the Hib
      immunization, Latin America countries will be faced with increased nontypeable H.
      influenzae infection. Although standing by the nontypeable H. influenzae vaccine,
      in this novel epidemiological scenario of post-Hib vaccination in Latin America
      settings there is a need to improve H. influenzae resistance monitoring to guide
      clinicians to choose efficacious antimicrobial therapy.

PMID- 11822781
TI  - The epidemiology of methicillin-resistant Staphylococcus aureus at a Saudi
      university hospital.
AB  - To determine changes in the epidemiology of methicillin-resistant Staphylococcus
      aureus (MRSA), a prospective study was conducted for a 30-month period in a
      university hospital in the eastern province of Saudi Arabia. Of 1,096
      Staphylococcus aureus isolates identified, 92 (8.4%) were MRSA. Seventy-two (78%)
      of the 92 isolates were from nosocomial cases and 20 (22%) isolates were from
      community cases. Thirteen (14%) of 20 patients with community-acquired MRSA had
      no discernible risk factors. The community-acquired MRSA from patients without
      identified risk were susceptible to a greater number of antimicrobials compared
      with isolates obtained from patients with community-acquired MRSA with identified
      risk or with nosocomially acquired MRSA. No strain resistant to vancomycin was
      recorded in this study. The impact of these organisms could be substantial if
      they become more frequent or widespread.

PMID- 11822782
TI  - Low molecular weight heparin inhibits tumor necrosis factor alpha-induced
      leukocyte rolling.
AB  - OBJECTIVE: Heparins may exert several anti-inflammatory actions. This study
      investigated the impact of low molecular weight heparin (LMWH) on tumor necrosis
      factor (TNF)-alpha-provoked leukocyte rolling, adhesion and extravascular
      accumulation. MATERIALS AND METHODS: Leukocyte-endothelium interactions and
      tissue accumulation of leukocytes were induced by TNF-alpha in Balb/c mice and
      analyzed by the use of intravital microscopy in the mouse cremaster muscle
      microcirculation. RESULTS: We observed that administration of 5000 units/kg of
      LMWH, but not 50 and 500 units/kg, markedly reduced TNF-alpha-induced leukocyte
      rolling, adhesion and tissue infiltration. Notably, when LMWH was given after TNF
      alpha only leukocyte rolling was reduced and no effect was observed on firm
      adhesion of leukocytes. CONCLUSIONS: Taken together, these findings indicate that
      LMWH inhibits TNF-alpha-induced leukocyte accumulation by inhibiting the rolling
      adhesive interaction which may help explain the anti-inflammatory effects of
      LMWH.

PMID- 11822783
TI  - Estrogens ameliorate remote organ inflammation induced by burn injury in rats.
AB  - OBJECTIVE AND DESIGN: The present study was designed to investigate the role of
      sex steroids in burn-induced remote organ injury. MATERIAL OR SUBJECTS: Male
      Wistar albino rats were given burn trauma (n=39), and underwent castration or
      sham operation at 2 h following the burn injury. TREATMENT: Rats were injected sc
      with either 17beta estradiol benzoate (E2, 10 mg/kg) or an androgen receptor
      blocker cyproterone acetate (CPA, 25 mg/kg) or vehicle, immediately after burn
      and at 12 h. METHODS: At 24 h of burn insult, rats were decapitated. Blood
      samples for RIA of testosterone, estradiol and tumor necrosis factor (TNF)-alpha
      and the tissue samples for myeloperoxidase activitiy (MPO) were taken. ANOVA
      student's t test was used for statistical analysis. RESULTS: Castration,
      antiandrogen and E2 treatments increased plasma estradiol levels and depressed
      burn-induced elevation in serum TNF-alpha levels. In the liver and lung, burn
      induced increase in MPO was reduced by E2 and castration, while CPA was effective
      in reducing neutrophil infiltration only in the liver. CONCLUSION: We propose
      that treatment with estrogens or antiandrogens might be applicable in clinical
      situations to ameliorate systemic inflammation induced by burn.

PMID- 11822784
TI  - Activated Ras modifies the proliferative response of rheumatoid synovial cells to
      TNF-alpha and TGF-alpha.
AB  - OBJECTIVE: To study the role of the Ras/mitogen-activated protein kinase (MAPK)
      pathway in the proliferative response of rheumatoid synovial fibroblast (RSF) to
      tumor necrosis factor (TNF)-alpha and transforming growth factor (TGF)-alpha.
      METHODS: V-Ki-ras gene was introduced into RSF using a retrovirus and the
      proliferative response of these cells to TNF-alpha or TGF-alpha was estimated by
      measuring the uptake of 3H-thymidine. The effect of a mitogen-activated protein
      kinase kinase (MEK) inhibitor, PD98059, was also investigated. RESULTS:
      Consistent with previous reports, TNF-alpha and TGF-alpha stimulated the
      proliferation of RSF. When the v-Ki-ras gene was expressed, the basal growth rate
      of these cells was increased, but their growth was suppressed by TNF-alpha or TGF
      alpha. The latter effect was abolished when the cells were exposed to a
      relatively low concentration of PD98059. CONCLUSION: Ras modulates the
      proliferative response of RSF to TNF-alpha and TGF-alpha.

PMID- 11822785
TI  - Clinical and biochemical response to single infusion of clodronate in active
      rheumatoid arthritis--a double blind placebo controlled study.
AB  - OBJECTIVE: To investigate the efficacy and tolerability of intravenous clodronate
      in patients with rheumatoid arthritis (RA). TREATMENT AND METHODS: Twenty-six
      patients with active RA were randomly allocated to receive either a single iv.
      infusion of placebo or 600 mg clodronate. Efficacy and safety were assessed
      weekly during the following three weeks by clinical and laboratory evaluations.
      RESULTS: Serum osteocalcin and carboxyterminal propeptide of type I procollagen
      (markers of bone metabolism) were significantly decreased in the clodronate group
      at the end of the study, whereas the indices of disease activity including number
      of swollen joints, number of tender joints, patient's and doctor's estimation of
      condition (visual analogue scale), erythrocyte sedimentation rate and serum C
      reactive protein level were not affected by clodronate treatment. No serious
      adverse effects were observed. CONCLUSIONS: A single infusion of clodronate in
      patients with RA was safe and caused a decline in the markers of bone metabolism,
      but this short-term treatment did not suppress disease activity. Results from
      recent clinical and preclinical studies, however, suggest that the anti
      inflammatory efficacy of clodronate requires liposome encapsulation.

PMID- 11822786
TI  - Estimation of acute flurbiprofen and ketoprofen toxicity in rat gastric mucosa at
      therapy-relevant doses.
AB  - OBJECTIVE: Since assessment of the acute gastrotoxicity of nonsteroidal
      antiinflammatory drugs (NSAIDs) in rats requires high doses of the drugs, we
      sought to establish an experimental model with which this adverse NSAID effect
      can be estimated at therapy-relevant doses. METHODS: The study was performed with
      racemic flurbiprofen-trometamol (R/S-FBP), its pure enantiomers S-FBP and R-FBP,
      and racemic ketoprofen-trometamol (R/S-KP). Two hours after administration of FBP
      or KP to Sprague-Dawley rats, HCl (0.5 M, 10 ml/kg) was given intragastrically
      (IG), and the haemorrhagic lesion area in the gastric mucosa quantified 1 h post
      HCI. RESULTS: FBP amplified gastric acid injury in a dose-related manner, the
      rank order of potency being S-FBP > R/S-FBP >> R-FBP. While less than 1
      micromol/kg S-FBP and R/S-FBP aggravated acid injury, doses up to 50 micromol/kg
      failed to cause appreciable damage without subsequent HCl challenge. Similar
      observations were made with R/S-KP which at doses of > or = 1 micromol/kg
      aggravated gastric acid injury. There was no significant difference in the
      gastrotoxicity of FBP when the drug was administered subcutaneously or IG,
      whereas subcutaneously injected R/S-KP was slightly more toxic than IG R/S-KP.
      CONCLUSIONS: These data show that FBP- and KP-induced amplification of acid
      injury in the rat gastric mucosa is a sensitive assay whereby, with single drug
      dosing, the gastrotoxic potential of these and other NSAIDs may be estimated at
      therapy-relevant doses that in humans threaten mucosal integrity only following
      chronic use.

PMID- 11822787
TI  - Antibodies to PECAM-1 and glucocorticoids reduce leukocyte adhesion in adjuvant
      arthritis of the rat knee synovium in vivo.
AB  - OBJECTIVE AND DESIGN: To demonstrate the effect of monoclonal antibodies to the
      adhesion-molecule PECAM-1 (CD31) and of prednisolone on leukocyte adhesion in rat
      adjuvant arthritis. MATERIAL: Adjuvant arthritis was induced in male CD-rats
      (five groups of n = 6) 18 days prior to measurements. TREATMENT: Mouse-monoclonal
      antibody to rat CD-31 at 200 microg/kg or prednisolone at 24 mg/kg were
      administered i.v. 15 minutes prior to measurements. METHODS: Venules within the
      intact rat-knee synovium were focused by confocal laser scanning microscopy.
      Numbers of rolling and adherent leukocytes were assessed in vivo. RESULTS:
      Induction of arthritis significantly increased rolling and adherent leukocytes
      compared to healthy controls. Both monoclonal antibodies to PECAM-1 and
      prednisolone significantly reduced adherent, but not rolling leukocytes in
      arthritic animals. CONCLUSIONS: The method used is well suited for in vivo
      quantification of leukocyte adhesion under the influence of antiadhesive
      therapies. PECAM-1 might be an interesting target for novel therapies in
      rheumatoid arthritis.

PMID- 11822788
TI  - The effect of allergen-induced airway inflammation on airway remodeling in a
      murine model of allergic asthma.
AB  - OBJECTIVE AND DESIGN: We examined the effect of airway inflammation on airway
      remodeling and bronchial responsiveness in a mouse model of allergic asthma.
      MATERIALS AND METHODS: BALB/c mice were sensitized to ovalbumin (OA), and exposed
      to aerosolized OA (0.01, 0.1 and 1%). Twenty-four hours after the final antigen
      challenge, bronchial responsiveness was measured, and bronchoalveolar lavage
      (BAL) and histological examinations were carried out. RESULTS: Repeated antigen
      exposure induced airway inflammation, IgE/IgG1 responses, epithelial changes,
      collagen deposition in the lungs, subepithelial fibrosis associated with
      increases in the amount of transforming growth factor (TGF)-beta1 in BAL fluid
      (BALF), and bronchial hyperresponsiveness to acetylcholine. The number of
      eosinophils in BALF was significantly correlated with TGF-beta1 production in
      BALF and the amount of hydroxyproline. Furthermore, significant correlations were
      found between these fibrogenic parameters and the bronchial responsiveness.
      CONCLUSION: These findings demonstrated that in this murine model airway
      eosinophilic inflammation is responsible for the development of airway remodeling
      as well as bronchial hyperresponsiveness in allergic bronchial asthma.

PMID- 11822789
TI  - Differential expression of CCR3 ligand mRNA in guinea pig lungs during allergen
      induced inflammation.
AB  - OBJECTIVE AND DESIGN: The gene expression profile of CCR3 ligands, eotaxin,
      RANTES, and monocyte chemoattractant protein-3 (MCP-3), was examined in normal
      and inflamed guinea pig lungs. MATERIAL: Male Hartley guinea pigs (n = 49).
      METHODS: Pulmonary mRNA was obtained from naive animals, animals treated with
      intravenous lipopolysaccharide administration, and animals repeatedly exposed to
      aerosolized allergen (ovalbumin). Northern analysis was performed to quantify
      pulmonary expression of eotaxin, RANTES, and MCP-3 mRNA. Pulmonary eosinophil
      peroxidase (EPO) activity was measured to quantify eosinophil accumulation.
      RESULTS: Eotaxin and RANTES mRNAs, but not MCP-3 mRNA, were constitutively
      expressed in guinea pig lungs. Lipopolysaccharide treatment increased MCP-3 mRNA
      expression, but not eotaxin or RANTES mRNA. In contrast, allergen exposure in
      sensitized animals caused an increase in eotaxin mRNA, which demonstrated good
      temporal and quantitative correlation with pulmonary EPO activity, but not in MCP
      3 or RANTES mRNA. CONCLUSIONS: Guinea pig CCR3 ligands demonstrated different
      gene expression profiles in normal and inflamed airways, suggesting that they
      play different physiological and pathophysiological roles in the airway.

PMID- 11822790
TI  - Smallest real difference, a link between reproducibility and responsiveness.
AB  - The aim of this study is to show the relationship between test-retest
      reproducibility and responsiveness and to introduce the smallest real difference
      (SRD) approach, using the sickness impact profile (SIP) in chronic stroke
      patients as an example. Forty chronic stroke patients were interviewed twice by
      the same examiner, with a 1-week interval. All patients were interviewed during
      the qualification period preceding a randomized clinical trial. Test-retest
      reproducibility has been quantified by the intraclass correlation coefficient
      (ICC). the standard error of measurement (SEM) and the related smallest real
      difference (SRD). Responsiveness was defined as the ratio of the clinically
      relevant change to the SD of the within-stable-subject test-retest differences.
      The ICC for the total SIP was 0.92, whereas the ICCs for the specified SIP
      categories varied from 0.63 for the category 'recreation and pastime' to 0.88 for
      the category 'work'. However, both the SEM and the SRD far more capture the
      essence of the reproducibility of a measurement instrument. For instance, a total
      SIP score of an individual patient of 28.3% (which is taken as an example, being
      the mean score in the study population) should decrease by at least 9.26% or
      approximately 13 items, before any improvement beyond reproducibility noise can
      be detected. The responsiveness to change of a health status measurement
      instrument is closely related to its test-retest reproducibility. This
      relationship becomes more evident when the SEM and the SRD are used to quantify
      reproducibility, than when ICC or other correlation coefficients are used.

PMID- 11822791
TI  - Why are we weighting? The role of importance ratings in quality of life
      measurement.
AB  - Many Quality of Life (QoL) instruments ask respondents to rate a number of life
      domains in terms of satisfaction and personal importance, and derive weighted
      satisfaction scores by multiplying the two ratings. This paper demonstrates that
      this practice is both undesirable and unnecessary. QoL domains are selected on
      the basis of their inherent importance, rendering separate importance rating
      partially redundant. Weighted scores present difficulties in interpretation.
      Further, we show that multiplicative composites have undesirable psychometric
      properties. There is evidence that multiplicative composites have little or no
      advantage over unweighted ratings in correlational or predictive studies. Apart
      from the face validity and the intuitive appeal of multiplying satisfaction
      ratings by importance ratings, there appear to be no sound reasons for doing so,
      and several good reasons not to do so.

PMID- 11822792
TI  - A longitudinal study of health related quality of life and utility measures in
      patients with advanced breast cancer.
AB  - Health related quality of life (HRQOL) measures are now accepted as indicators of
      efficacy in the palliative treatment of cancer. Utility measures may also provide
      valuable information yet they have been applied less frequently. To assess the
      application of a time trade-off (TTO) utility measure and its concordance with
      the Spitzer uniscale and quality of life index (QLI) 38 women with advanced,
      symptomatic breast cancer were studied over a 12 month period. The correlation
      coefficient for QLI and TTO values was 0.54 and for uniscale and TTO 0.62. Using
      generalized estimating equations the regression of TTO scores on QLI and uniscale
      scores was significant at baseline. In longitudinal analyses results were
      significant only for QLI. Although all participants completed the HRQOL measures
      only 24 (63%) were prepared to trade time. The remaining 14 (32%) stated they
      felt too well to trade. Those prepared to trade time recorded significantly worse
      mean HRQOL scores throughout the study compared to those who felt too well to
      trade and had tumors which showed a poorer response to therapy. In this
      preliminary study utility and HRQOL scores were generally favorable throughout
      the 12 month study period and showed fair to moderate concordance. Further
      research in larger patient groups is required to better define the relationships
      between utility and HRQOL measures.

PMID- 11822793
TI  - Measuring women's preferences for breast cancer treatments and BRCA1/BRCA2
      testing.
AB  - In establishing decision models in the treatment and prevention of breast cancer,
      it is important to evaluate patients' preferences for such interventions. The
      objectives of the present study were: (i) to characterize women's preferences for
      breast cancer treatments and BRCA1/BRCA2 testing, using the rating scale and
      standard gamble techniques; and (ii) to identify factors associated with these
      quality of life indices. Data were collected from women with breast cancer (n =
      60), high-risk relatives of women with breast cancer (n = 58), and women in the
      general population (n = 51). Regardless of group membership, participants
      favoured treatment and prevention options that involved minimal physical
      invasiveness. Women with breast cancer rated lumpectomy and radiation treatment
      more highly than high-risk relatives and women in the general population.
      Preferences did not differ according to participants' intentions to undergo BRCA
      testing. Age was the only demographic variable associated with health state
      preferences. These findings hold implications for the application of patient
      preferences to clinical decision making.

PMID- 11822794
TI  - Proxy reliability: health-related quality of life (HRQoL) measures for people
      with disability.
AB  - OBJECTIVES: Research and surveillance activities sometimes require that proxy
      respondents provide key exposure or outcome information, especially for studies
      of people with disability (PWD). In this study, we compared the health-related
      quality of life (HRQoL) responses of index PWD to proxies. METHODS: Subjects were
      selected from nursing home, other assisted living residences, and from several
      clinic samples of PWD. Each index identified one or more proxy respondents.
      Computer-assisted interviews used a random order of measures. Proxy reliability
      was measured by intraclass correlation (ICC) and kappa statistics. HRQoL measures
      tested included the surveillance questions of the Behavioral Risk Factor
      Surveillance System (BRFSS), basic and instrumental activities of daily living
      (ADLs and IADLs), medical outcomes study short-form 36 and 12 (SF-36 and SF-12).
      RESULTS: A total of 131 index-proxy sets were completed. In general, agreement
      and reliability of proxy responses to the PWD tended to be best for relatives,
      with friends lower, and health care proxies lowest. For example, the ICC for the
      physical functioning scale of the SF-36 was 0.68 for relatives, 0.51 for friends,
      and 0.40 for healthcare proxies. There was a tendency for proxies to overestimate
      impairment and underestimate HRQoL. This pattern was reversed for measures of
      pain, which proxies consistently underestimated. The pattern among instruments,
      proxy types, and HRQoL domains was complex, and individual measures vary from
      these general results. CONCLUSIONS: We suggest caution when using proxy
      respondents for HRQoL, especially those measuring more subjective domains.

PMID- 11822795
TI  - Swedish population health-related quality of life results using the EQ-5D.
AB  - Health-related quality of life (HRQoL) measured on population level may be useful
      to guide policies for health. This study aims to describe the HRQoL; in EQ-5D
      dimensions, mean rating scale (RS) scores and mean EQ-5D index values, in the
      general population, by certain disease and socio-economic groups, in Stockholm
      County 1998. The EQ-5D self-classifier and a RS were included in the 1998 cross
      sectional postal Stockholm County public health survey to a representative sample
      (n = 4950, 20-88 years), 63% response rate. Mean RS score ranged from 0.90 (20-29
      years) to 0.69 (80-88 years), mean EQ-5D index value ranged from 0.89 (20-29
      years) to 0.74 (80-88 years). For different diseases mean RS scores ranged from
      0.80 (asthma) to 0.69 (angina pectoris), mean EQ-5D index values ranged from 0.79
      (asthma) to 0.66 (low back pain). The mean health state scores (RS and EQ-5D
      index) were 0.06 lower in the unskilled manual group than in the higher non
      manual group after controlling for age and sex (p < 0.0001). This difference was
      0.03 after controlling also for different diseases (p < 0.0001). In conclusion,
      our results show that the HRQoL varies greatly between socio-economic and disease
      groups. Furthermore, after controlling for age, sex and disease, HRQoL is lower
      in manual than in non-manual groups.

PMID- 11822796
TI  - Psychometric properties of the RAND-36 among three chronic diseases (multiple
      sclerosis, rheumatic diseases and COPD) in The Netherlands.
AB  - OBJECTIVE: In this article, psychometric properties both of the total RAND-36 and
      of its subscales, such as unidimensionality, differential item functioning (DIF
      or item bias), homogeneity and reliabilities, are examined. METHODS: The data
      from populations with three chronic illnesses, multiple sclerosis (n = 448),
      rheumatism (n = 336) and COPD (n = 259), have been collected in different parts
      of the Netherlands. The main technique used was Mokken scale analysis for
      polytomous items. RESULTS: All subscales of the RAND-36 appeared to be
      unidimensional. For the subscales 'mental health' and general health perceptions'
      some minor indications of DIF for the different chronic illnesses were found.
      Reliabilities of almost all subscales in all subpopulations were higher than
      0.80, while the homogeneities of almost all subscales in all subpopulations were
      higher than 0.50, indicating 'strong unidimensional, hierarchical scales'.
      CONCLUSIONS: In general, the subscales of the RAND-36 can be used to compare
      persons with different chronic illnesses. The subscale 'general health
      perceptions' did not function as well as would be preferred.

PMID- 11822797
TI  - Canine anal sac adenocarcinomas: clinical presentation and response to therapy.
AB  - A retrospective study of 43 dogs with anal sac adenocarcinoma (ASAC) was
      performed to characterize the clinical presentation and response to treatment.
      Clinical signs at presentation varied considerably, with signs related either to
      sublumbar nodal metastasis (tenesmus or constipation) or hypercalcemia (polyuria
      polydipsia and anorexia) being the most frequent findings. At the time of
      presentation, 23 (53%) dogs had hypercalcemia and 34 (79%) had metastases, with
      the regional lymph nodes (31 dogs, 72%) being the most common site of metastasis.
      A variety of chemotherapeutic agents were administered, with partial remission
      (PR) recorded in 4 of 13 (31%) dogs treated with cisplatin and in 1 of 3 (33%)
      dogs treated with carboplatin. The median survival for all dogs was 6 months
      (range, 2 days-41 months). There was no statistical association between the
      presence of hypercalcemia and survival, although the power of the study to detect
      an increase in survival of 3 months was low (.33). We conclude that platinum
      chemotherapy has antitumor activity in canine apocrine gland carcinoma and that
      further study of these agents is warranted.

PMID- 11822798
TI  - Matrix metalloproteinase activity in tumor, stromal tissue, and serum from cats
      with malignancies.
AB  - Matrix metalloproteinases (MMPs) are enzymes that play key roles in angiogenesis,
      tumor invasion, and metastasis in a wide variety of species. The purpose of this
      study was to evaluate pro and active MMP 2 and 9 concentrations in tumor, normal
      stromal tissue, and serum from tumor-bearing cats. We hypothesized that serum
      concentrations of pro and active forms of MMPs 2 and 9 would be predictive of MMP
      concentrations in tumor tissue and that these MMP concentrations would correlate
      with the histopathologic grade of the malignancies. Pro and active forms of MMPs
      2 and 9 were determined by gelatin zymography and subsequent computerized
      densitometry from tumor and nearby stromal tissue and serum from 49 cats with
      various malignancies. The serum concentrations of MMPs from these tumor-bearing
      cats were compared with serum concentrations of MMPs from 44 normal cats of
      similar age and gender. Measurable concentrations of MMPs 2 and 9 were found
      within tumor, stromal, and serum samples. Mean concentrations of total pro and
      active MMPs 2 and 9 within tumor tissue were significantly higher (P values
      <.0001, .0031, <.001, and .0064, respectively) when compared with stromal tissue
      from the same animals. Serum MMP concentrations from tumor-bearing cats were
      higher than those from normal cats. Poor correlation was found between serum MMP
      concentrations and tissue MMP concentrations of increasing histologic grades of
      malignancies.

PMID- 11822799
TI  - Thyroid-stimulating hormone in adult euthyroid and hypothyroid horses.
AB  - The purpose of this study was to validate a thyroid-stimulating hormone (TSH)
      assay in a model of equine hypothyroidism. Thyrotropin-releasing hormone (TRH)
      stimulation tests were performed in 12 healthy adult mares and geldings, aged 4
      to greater than 20 years. before and during administration of the antithyroid
      drug propylthiouracil (PTU) for 6 weeks. Serum concentrations of equine TSH,
      total and free thyroxine (T4), and total and free triiodothyronine (T3) were
      measured. Before PTU administration, mean +/- standard deviation baseline
      concentrations of TSH were 0.40 +/- 0.29 ng/mL. TSH increased in response to TRH,
      reaching a peak concentration of 0.78 +/- 0.28 ng/mL at 45 minutes. Total and
      free T4 increased from 12.9 +/- 5.6 nmol/L and 12.2 +/- 3.5 pmol/L to 36.8 +/-
      11.4 nmol/L and 23.1 +/- 5.9 pmol/L, respectively, peaking at 4-6 hours. Total
      and free T3 increased from 0.99 +/- 0.51 nmol/L and 2.07 +/- 1.14 pmol/L to 2.23
      +/- 0.60 nmol/l and 5.78 +/- 1.94 pmol/L, respectively, peaking at 2-4 hours.
      Weekly measurements of baseline TSH and thyroid hormones during PTU
      administration showed that total and free T, concentrations fell abruptly and
      remained low throughout PTU administration. Total and free T4 concentrations did
      not decrease dramatically until weeks 5 and 4 of PTU administration,
      respectively. A steady increase in TSH concentration occurred throughout PTU
      administration, with TSH becoming markedly increased by weeks 5 and 6 (1.46 +/-
      0.94 ng/mL at 6 weeks). During weeks 5 and 6 of PTU administration, TSH response
      to TRH was exaggerated, and thyroid hormone response was blunted. Results of this
      study show that measurement of equine TSH in conjunction with thyroid hormone
      measurement differentiated normal and hypothyroid horses in this model of equine
      hypothyroidism.

PMID- 11822800
TI  - The 1st balloon valvuloplasty: an historical note.
AB  - Balloon valvuloplasty (BV) is currently the treatment of choice for pulmonic
      stenosis in humans and dogs. Before permission was obtained to attempt the 1st BV
      in a child in 1982, the safety and efficacy of the procedure were tested in 1980
      in an English Bulldog with spontaneous pulmonic stenosis. A fatal outcome would
      have caused indefinite postponement of BV in human patients, a procedure that
      currently benefits over 25,000 patients a year worldwide. This article describes
      the initial test procedure and its fortunate outcome in spite of unrecognized
      coronary anomalies in the bulldog. A small balloon was used in the test
      procedure, and fatal disruption of the anomalous left coronary artery (CA) did
      not occur as it has in several bulldogs since that time.

PMID- 11822801
TI  - Host responses to Cryptosporidium infection.
AB  - Cryptosporidium is a clinically and economically important infection whose
      pathogenic effect begins with colonization of the intestinal epithelium. Despite
      intensive efforts, a consistently effective therapy for the infection has yet to
      be identified. Morbidity and mortality results from ongoing loss of absorptive
      epithelium, which leads to villous atrophy and malabsorption and release of
      inflammatory mediators that stimulate electrolyte secretion and diarrhea. With
      further clarification of the mechanisms underlying enterocyte malfunction in
      Cryptosporidium infection, it should be possible to design rational nutritional
      and pharmacologic therapies to enhance nutrient and water absorption, promote the
      clearance of infected enterocytes, and restore normal villus architecture and
      mucosal barrier function.

PMID- 11822802
TI  - Visceral leishmaniasis in a New York foxhound kennel.
AB  - Although endemic throughout much of the world, autochthonous visceral
      leishmaniasis has been reported on only 3 previous occasions in North America.
      After diagnosis of visceral leishmaniasis in 4 foxhounds from a kennel in
      Dutchess County, New York (index kennel), serum and ethylenediamine-tetraacetic
      acid (EDTA)-anticoagulated blood were collected from the remaining 108 American
      or cross-bred foxhounds in the index kennel and from 30 Beagles and Basset Hounds
      that were periodically housed in the index kennel. Samples were analyzed for
      antibodies to or DNA of tickborne disease pathogens and Leishmania spp. Most dogs
      had antibodies to Rickettsia spp., Ehrlichia spp., Babesia spp., or some
      combination of these pathogens but not to Bartonella vinsonii (berkhoffi).
      However, DNA of rickettsial, ehrlichial, or babesial agents was detected in only
      9 dogs. Visceral leishmaniasis was diagnosed in 46 of 112 (41%) foxhounds from
      the index kennel but was not diagnosed in any of the Beagles and Basset Hounds. A
      positive Leishmania status was defined by 1 or more of the following criteria: a
      Leishmania antibody titer > or = 1:64, positive Leishmania polymerase chain
      reaction (PCR), positive Leishmania culture, or identification of Leishmania
      amastigotes by cytology or histopathology. The species and zymodeme of Leishmania
      that infected the foxhounds was determined to be Leishmania infantum MON-1 by
      isoenzyme electrophoresis. Foxhounds that were > 18 months of age or that had
      traveled to the southeastern United States were more likely to be diagnosed with
      visceral leishmaniasis. Transmission of Leishmania spp. in kennel outbreaks may
      involve exposure to an insect vector, direct transmission, or vertical
      transmission.

PMID- 11822803
TI  - Evaluation of cystatin C as an endogenous marker of glomerular filtration rate in
      dogs.
AB  - Cystatin C is a cysteine protease inhibitor produced by all nucleated cells. It
      is freely filtered by the glomerulus and is unaffected by nonrenal factors such
      as inflammation and gender. Because of greater sensitivity and specificity,
      cystatin C has been proposed to replace creatinine as a marker of glomerular
      filtration rate (GFR) in humans. The aims of this study were to validate an
      automated assay in canine plasma and to evaluate the usefulness of cystatin C as
      a marker of GFR in dogs. Western blotting was used to demonstrate cross
      reactivity of an anti-human cystatin C antibody. An immunoturbidimetric assay was
      used to detect cystatin C in 25 clinically healthy dogs and 25 dogs with renal
      failure. Mean cystatin C concentration in the healthy dogs and the dogs with
      renal failure was 1.08 +/- 0.16 mg/L and 4.37 +/- 1.79 mg/L respectively. Intra-
      and interassay variability was <5%. The assay was linear (r = .974) between 0.14
      and 7.53 mg/L. Both cystatin C and creatinine concentrations were measured in
      banked, frozen serum from 20 remnant kidney model dogs and 10 volume-depleted
      dogs for which GFR measurements by exogenous creatinine clearance had been
      determined previously. In the remnant kidney model, cystatin C was better
      correlated with GFR than creatinine (r = .79 versus .54) but was less well
      correlated with GFR in volume-depleted dogs (r = .54 versus .95). GFR
      measurements were repeated in the remnant kidney model dogs 60 days after initial
      GFR measurements. At this time, cystatin C and creatinine concentrations
      correlated equally well with GFR (r = .891 versus .894, respectively). Cystatin C
      concentration is a reasonable alternative to creatinine for screening dogs with
      decreased GFR due to chronic renal failure.

PMID- 11822804
TI  - In-house caseload and education of veterinary students in production animal
      medicine.

PMID- 11822805
TI  - Dilated cardiomyopathy in juvenile Portuguese Water Dogs.
AB  - Dilated cardiomyopathy recently has been recognized in juvenile Portuguese Water
      Dogs. The purpose of this study was to evaluate unaffected and affected puppies
      by physical examination, electrocardiogram (ECG), echocardiogram, specific
      biochemical assays, and ultrastructure to document disease progression and to
      develop a method of early detection. Results of segregation analysis were
      consistent with autosomal recessive inheritance. Of 124 puppies evaluated
      clinically and echocardiographically, 10 were affected. No significant
      differences were found between unaffected and affected puppies for blood and
      myocardial carnitine or taurine concentrations, serum chemical variables, results
      of ophthalmological examinations, ECGs, or measurement of urine metabolites.
      Ultrastructural examination of myocardium from affected dogs revealed
      myofibrillar atrophy and small regions of myofibrillar degeneration, most
      prominently at the region of the intercalated discs. Only echocardiography
      allowed detection of affected puppies before clinical signs became evident.
      Echocardiography revealed a significant difference in the shortening fraction, E
      point to septal separation, and the end systolic and diastolic left ventricular
      internal diameters. Affected puppies were detected 1-4 weeks before the
      development of acute congestive heart failure.

PMID- 11822807
TI  - Effect of body position on the 6-lead ECG of dogs.
AB  - ECGs recorded from dogs show characteristic morphology and changes in morphology
      with various disease states. These changes are determined by comparing individual
      recordings to reference ranges established from recordings obtained from normal
      dogs in right lateral (RL) recumbency. Using these reference ranges for ECGs
      recorded from dogs in other positions may not be valid. We compared ECG complexes
      from 39 normal dogs obtained in RL, left lateral (LL), and standing (ST) body
      positions. ECGs from dogs in ST position showed increased Q-wave and R-wave
      amplitudes in leads I and II, increased R-wave and S-wave amplitudes in leads aVR
      and aVL, and decreased R-wave and S-wave amplitudes in lead III when compared
      with recordings obtained in RL position. ECGs from dogs in LL position showed
      increased R-wave amplitude in leads II, III, and aVF and S-wave amplitude in lead
      aVL but decreased R-wave amplitude in lead aVR when compared with recordings
      obtained in RL position. The mean electrical axis (MEA) shifted to the left in ST
      position but remained within the normal range in LL position. We determined that
      both a change in the relative position of the recording electrodes with respect
      to the heart as well as a change in intrathoracic cardiac position contributed to
      these changes. P-wave amplitude, P-R and S-T intervals, and QRS complex durations
      remained unaltered by changes in body position. Our findings indicate that ECGs
      of dogs recorded in RL, LL, and ST positions yield dramatically different
      results, and investigators should use position-specific reference ranges to
      minimize potential misinterpretation of ECG results.

PMID- 11822806
TI  - Cardiac troponins in canine babesiosis.
AB  - This study compared the sensitivity of ECG and cardiac troponins to predict
      cardiac histopathological changes, clinical severity, and survival in canine
      babesiosis. One control group (n = 9) and 4 groups of dogs with mild
      uncomplicated babesiosis (n = 8), severe uncomplicated babesiosis (n = 9),
      complicated babesiosis (n = 8), and babesiosis and concurrent immune-mediated
      hemolytic anemia (IMHA) (n = 9) were studied. A 1-minute lead II ECG was
      recorded, and cardiac troponin I (cTnI) and T (cTnT) concentrations in plasma
      were measured. cTnI concentrations were significantly higher in the complicated
      (mean, 9.9; SE, +/-5.76) and concurrent IMHA (mean, 6.53; SE, +/-4.32) groups and
      in the 3 dogs that died of the disease (mean, 22.17; SE, +/-12.85) than in the
      control dogs (concentration below detection limit of test, -0.3 ng/mL). The 3
      nonsurvivors had the most severe cardiac histopathological changes, but no
      arrhythmia and minimal other ECG changes. Dogs with babesiosis developed a
      variety of ECG abnormalities, but the abnormalities were not associated with
      disease severity, outcome, or plasma cardiac troponin concentrations. The
      exception was the presence of ventricular premature complexes (VPCs), which were
      associated with high cardiac troponin concentrations. This study showed an
      association between cTnI concentration and histological changes, clinical
      severity, and survival and no correlation between ECG abnormalities and
      histological changes or biochemical evidence of myocardial damage as reflected by
      cTnI concentrations. From this study, it was concluded that the analysis of
      plasma cTnI is a feasible and sensitive test and is superior to cTnT in
      diagnosing cardiac involvement in dogs with babesiosis.

PMID- 11822808
TI  - Factors related to in-house agricultural animal caseloads in US veterinary
      teaching hospitals.
AB  - A retrospective observational study was conducted to determine whether
      agricultural animal caseloads at veterinary teaching hospitals declined between
      1995 and 1998. Thereafter, the effect of organizational and demographic factors
      on 1998 in-house agricultural animal caseloads was examined. Caseload data were
      obtained from the American Association of Veterinary Medical Colleges.
      Demographic and organizational data were obtained by surveys, telephone
      interviews, and web-based resources. Complete data were available from 25
      veterinary colleges, and data from these schools were used in subsequent
      analyses. In 1998, in-house food animal caseload decreased relative to 1995 in 17
      schools and increased relative to 1995 in 8 schools. This trend was not
      significant (P = .053); however, the power of the test was limited (.50). Mean
      1998 caseload was 886 +/- 504. Among schools with a discipline-based
      organizational structure, annual mean caseload was 464 +/- 220. Among schools
      with a species-based organizational structure, mean caseload was 1,167 +/- 463.
      The regression model that best predicted caseload was a forward-stepping model
      that included only organizational structure as an independent variable. No
      additional independent variable was significantly associated with caseload.

PMID- 11822809
TI  - First-pass nuclear angiocardiography in the evaluation of patent ductus
      arteriosus in dogs.
AB  - First-pass nuclear angiocardiography (FPNA) was performed in 5 normal dogs and in
      19 dogs with left-to-right shunting patent ductus arteriosus (PDA). Affected dogs
      were evaluated before and after an occlusion procedure (surgical ligation or
      transarterial coil embolization). Two methods of analysis were used to evaluate
      the pulmonary time-activity curves and assess the magnitude of the shunt. One
      method involved the calculation of a simple count ratio (C2:C1). The other method
      used gamma variate modeling to estimate the ratio of pulmonary to systemic blood
      flow (QP:QS). Values for normal dogs (mean +/- SD) were C2:C1 = 0.39 +/- 0.11 and
      QP:QS = 1.10 +/- 0.03. Values for affected dogs were C2:C1 = 0.59 +/- 0.17, QP:QS
      = 2.01 +/- 0.46 before intervention and QP:QS = 1.21 +/- 0.17, C2:C1 = 0.42 +/-
      0.12 after intervention. Both methods detected significant differences between
      normal and affected dogs (QP:QS, t-test, P < .001; C2:C1; t-test; P = .018) and
      between affected dogs pre- and postocclusion (QP:QS. paired t-test, P < .001;
      C2:C1, paired t-test, P = .002). However, QP:QS was a better separator of normal
      from affected animals. First-pass nuclear angiocardiography, by the gamma variate
      method, may be a useful, adjunct diagnostic test in evaluation of animals with
      left-to-fight shunting PDA, particularly in animals with residual shunting after
      an occlusion procedure.

PMID- 11822810
TI  - Efficacy of enalapril for prevention of congestive heart failure in dogs with
      myxomatous valve disease and asymptomatic mitral regurgitation.
AB  - We evaluated the long-term effect of early angiotensin-converting enzyme (ACE)
      inhibition (enalapril maleate) as monotherapy to postpone or prevent congestive
      heart failure (CHF) in asymptomatic dogs with mitral regurgitation (MR)
      attributable to myxomatous valvular disease (MVD) in a prospective, randomized,
      double-blinded, placebo-controlled multicenter trial involving 14 centers in
      Scandinavia. Two hundred twenty-nine Cavalier King Charles (CKC) Spaniels with MR
      attributable to MVD but no signs of CHF were randomly allocated to treatment with
      enalapril 0.25-0.5 mg daily (n = 116) or to placebo groups (n = 113). Each dog
      was evaluated by physical examination, electrocardiography, and thoracic
      radiography at entry and every 12 months (+/-30 days). The number of dogs
      developing heart failure was similar in the treatment and placebo groups (n = 50
      [43%] and n = 48 [42%], respectively; P = .99). The estimated means, adjusted for
      censored observations, for the period from initiation of therapy to heart failure
      were 1,150 +/- 50 days for dogs in the treatment group and 1,130 +/- 50 days for
      dogs in the placebo group (P = .85). When absence or presence of cardiomegaly at
      the entrance of the trial was considered, there were still no differences between
      the treatment and placebo groups (P = .98 and .51, respectively). Multivariate
      analysis showed that enalapril had no significant effect on the time from
      initiation of therapy to heart failure (P = .86). Long-term treatment with
      enalapril in asymptomatic dogs with MVD and MR did not delay the onset of heart
      failure regardless of whether or not cardiomegaly was present at initiation of
      the study.

PMID- 11822811
TI  - Ivermectin toxicity in 17 collies.
AB  - Ivermectin is widely used in veterinary medicine as an anthelminthic and
      generally has a wide margin of safety, but Collies are prone to ivermectin
      toxicity. Two groups of Collies were presented to the University of California
      Veterinary Medical Teaching Hospital (VMTH) with ivermectin toxicity. The medical
      records of the 2 groups of Collies were reviewed retrospectively. Group I
      comprised 5 adult Collies that received at least 400 microg/kg ivermectin p.o.
      and were presented to the VMTH 3 hours after intoxication. These Collies showed
      marked clinical signs on presentation. Three of these dogs required mechanical
      ventilation and were euthanized for financial reasons; the remaining 2 dogs were
      comatose but recovered in 5-7 days. Group II was comprised of 12 adult Collies
      presented to the VMTH 2 days (n = 10) and 5 days (n = 2) after subcutaneous
      injection of 200-250 microg/kg ivermectin. These animals showed greater variation
      in severity of illness among individuals; 5 animals progressed to stupor or coma,
      whereas 4 animals remained ambulatory. Most of these dogs' clinical signs
      deteriorated from the day of intoxication until approximately day 6, from which
      time they showed gradual but steady improvement. All of the Collies in this group
      survived, but it took 3 weeks for most of them to recover. Collies suffering from
      ivermectin toxicity can have a severe and prolonged clinical course requiring
      intensive nursing care. Respiratory, cardiovascular, and nutritional support may
      all be required. With appropriate care, however, the prognosis for complete
      recovery is good.

PMID- 11822813
TI  - Promoting angiogenesis in engineered tissues.
AB  - There is a tremendous need for organs and tissues to replace those lost due to
      diseases or trauma. In theory, transplanting cells on biomaterial matrices can
      create functional tissue. A critical question, however, is how to supply cells
      embedded within large cell-polymer constructs with sufficient oxygen and
      nutrients to sustain their survival and proliferation, and allow for the
      integration of the developing tissue with the surrounding tissue. A rapid and
      high level of vascularization of transplanted polymer-cell matrices is essential
      in tissue engineering approaches to meet these challenges. This review summarizes
      the current approaches and materials under development in our laboratory to
      promote angiogenesis in engineered tissues.

PMID- 11822812
TI  - Absence of temporal lobe epilepsy pathology in dogs with medically intractable
      epilepsy.
AB  - Epilepsy is a common neurological problem in dogs. In some dogs, seizures cannot
      be controlled adequately with anticonvulsant medication. Temporal lobe epilepsy
      is the most common type of epilepsy in adult humans, it is frequently resistant
      to anticonvulsant therapy, and it is commonly associated with characteristic
      neuropathological abnormalities in the hippocampal dentate gyrus. We sought to
      test the hypothesis that dogs with medically intractable epilepsy have temporal
      lobe epilepsy. The hippocampi of 6 dogs that were euthanized because of chronic,
      recurrent seizures were compared with those of 8 nonepileptic controls. In
      control and epileptic dogs, stereological cell counting showed similar numbers of
      neurons in the hilus of the dentate gyrus, somatostatin immunoreactivity
      identified numerous immunopositive neurons in the hilus, and Timm staining showed
      the normal pattern of granule cell axon projections. These findings demonstrate a
      lack of hilar neuron loss and granule cell axon reorganization, suggesting that
      temporal lobe epilepsy is not a common cause of medically intractable epilepsy in
      dogs.

PMID- 11822814
TI  - Growth factor delivery for bone tissue engineering.
AB  - Bone is a dynamic tissue that undergoes significant turnover during the life
      cycle of an individual. Despite having a significant regenerative capability,
      trauma and other pathological scenarios commonly require therapeutic intervention
      to facilitate the healing process. Bone tissue engineering, where cellular and
      biological processes at a site are deliberately manipulated for a therapeutic
      outcome, offers a viable option for the treatment of skeletal diseases. In this
      review paper, we aim to provide a brief synopsis of cellular and molecular basis
      of bone formation that are pertinent to current efforts of bone healing.
      Different approaches for engineering bone tissue were presented with special
      emphasis on the use of soluble (diffusible) therapeutic agents to accelerate bone
      healing. The latter agents have been used for both local bone repair (i.e.
      introduction of agents directly to a site of repair) as well as systemic bone
      regeneration (i.e. delivery for regeneration throughout the skeletal system).
      Critical drug delivery and targeting issues pertinent for each mode of bone
      regeneration are provided. In addition, future challenges and opportunities in
      bone tissue engineering are proposed from the authors' perspective.

PMID- 11822815
TI  - Controlled release from coated polymer microparticles embedded in tissue
      engineered scaffolds.
AB  - The controlled release of proteins in tissue-engineered implants is being
      examined with the potential application to improve vascularization and hasten
      tissue growth. Bovine serum albumin (BSA), was encapsulated within poly(D,L
      lactic-co-glycolic acid) [PLGA] microparticles. The microparticles were coated
      with poly(vinyl alcohol) and incorporated into PLGA tissue-engineered scaffolds
      during fabrication. The release of BSA from PLGA microparticles, coated PLGA
      microparticles, and microparticles embedded in a porous PLGA scaffold was
      measured. We have developed a novel approach that will permit incorporation of
      coated polymeric microparticles during PLGA scaffold fabrication. Growth factors
      or drugs could be incorporated into the microparticles resulting in a long-term,
      controlled release.

PMID- 11822816
TI  - Insulin in tissue engineering of cartilage: a potential model system for growth
      factor application.
AB  - Investigation of novel experimental application systems for growth factors or
      other bioactive substances in tissue engineering is often limited by high costs
      of substances and would benefit from a defined and easily controllable model
      tissue system. Herein, we demonstrate a potential three-dimensional in vitro
      system using engineered cartilage as a model tissue and readily available insulin
      as a model drug. Previously it has been shown that insulin-like growth factor-I
      (IGF-I) has profound effects on tissue-engineered cartilage in vitro. Insulin is
      known to bind to the IGF-I receptor and to elicit significant responses in
      cartilage. In this study, bovine articular chondrocytes were seeded onto
      biodegradable polyglycolic acid (PGA) scaffolds and cultured for up to 7 weeks.
      Exogenous insulin (0.05-50 microg/ml) increased the growth rate and the
      glycosaminoglycan fraction of tissue-engineered cartilage, decreased the cell
      number in the tissue constructs, and improved the morphological appearance, with
      2.5 microg/ml being the most favorable concentration. The observed effects of
      insulin were similar to effects of IGF-I (0.05 microg/ml) and were in agreement
      with the reported binding constants of IGF-I and insulin at the IGF-I receptor.
      Besides the possibility to employ insulin as a potent substance to improve tissue
      engineered cartilage, the presented easily controllable in vitro system may be
      used in the future to evaluate experimental growth factor application devices
      using economically favorable insulin as a model protein.

PMID- 11822817
TI  - Triphasic release model for multilayered gelatin coatings that can recreate
      growth factor profiles during wound healing.
AB  - Multilayered gelatin coatings were created to mimic growth factor profiles that
      normally occur during fracture healing. A model was developed to relate
      crosslinking and loading of individual layers to protein release. Modeling was
      simplified by dividing release profiles into three phases. The diffusion
      controlled phase was determined by calculating periods of constant diffusivity
      for each homogeneous layer within devices. Diffusivity was a power law function
      of crosslinking. Fick's second law of diffusion was then used to determine
      release during the diffusion-controlled phase. Secondary diffusivity was
      determined by summing resistances of each successive homogeneous layer. The
      initial burst phase was defined as events proceeding the diffusion-controlled
      phase. Percentage of drug burst was a linear function of crosslinking. Release
      during the degradation-controlled phase, events following diffusion-controlled
      phase, was estimated based on first order hydrolysis of crosslinks. The model
      predicted time-variant release of differently labeled protein measured
      experimentally, and it can be used to design coatings to recreate the cascade of
      biomolecules that determine natural bone repair.

PMID- 11822818
TI  - Controlled release of hepatocyte growth factor from gelatin hydrogels based on
      hydrogel degradation.
AB  - This paper investigates the controlled release of hepatocyte growth factor (HGF)
      by biodegradable gelatin hydrogels and their HGF-induced angiogenic effect.
      Hydrogels of different degradabilities were prepared through chemical
      crosslinking gelatin with varied amounts of glutaraldehyde. When the gelatin
      hydrogels were radioiodinated and subcutaneously implanted into the back of mice,
      the remaining radioactivity of the hydrogels decreased with time. However, the
      remaining period became longer when the concentration of glutaraldehyde used for
      hydrogel preparation increased. Following implantation of gelatin hydrogels
      incorporating 125I-labeled HGF, the HGF radioactivity retained in the mouse
      subcutis for longer time periods as the glutaraldehyde concentration becomes
      higher. The time profile of HGF remaining in every gelatin hydrogel was in good
      accordance with that of hydrogel degradation, indicating HGF release as a result
      of hydrogel biodegradation. The gelatin hydrogel incorporating HGF histologically
      induced angiogenic change around the implanted hydrogel. Gelatin hydrogels
      incorporating 5 and 10 microg HGF significantly enhanced the number of
      capillaries newly formed around the implanted site. This was in marked contrast
      to free HGF of same dose form and HGF-free, empty gelatin hydrogel. The gelatin
      hydrogel incorporating HGF induced VEGF around the implanted site. In vitro
      bioassay revealed that HGF molecules interacting with gelatin, still exhibited
      the biological activity. The interacted HGF would be released from gelatin
      hydrogels only when they were degraded to generate water-soluble gelatin
      fragments. It is possible that the HGF associating gelatin fragments of
      bioactivating, results in induced angiogenic effect.

PMID- 11822819
TI  - Bioactive polymers for biohybrid artificial pancreas.
AB  - To address the solution for some of the obstacles, such as low insulin secretion,
      limited lifespan and aggregation of transplanted islets, encountered in
      developing a biohybrid artificial pancreas (BAP), polymeric materials including a
      reversible polymeric extracellular matrix (ECM), crystallized glucagon-like
      peptide-1, and oxygen carrying polymers, were prepared and their potential
      utilities in designing a compact and rechargeable BAP were investigated. For a
      synthetic, reversible ECM, high molecular weight N-isopropylacrylamide copolymer
      with a small amount of acrylic acid (2 mole%) was synthesized by conventional
      radical polymerization in benzene, and its aqueous solution above a critical
      polymer concentration displayed a sol-gel transition temperature near
      physiological temperature (33-35 degrees C) without noticeable hysteresis. The
      physicochemical properties of the gel with islet compatibility proved that the
      synthetic ECM is an appropriate matrix which can make a BAP rechargeable.
      Glucagon-like peptide-1 (GLP-1, 7-37) is known to have a strong stimulatory
      effect on insulin secretion, particularly at high glucose concentrations. When
      zinc-crystallized GLP-1 was entrapped along with islets in a hollow fiber
      macrocapsule device, insulin secretion was enhanced at a high glucose
      concentration (300 mg/dl) with a >85% increase in insulin secretion after an
      induction period. The cross-linked hemoglobin with difunctional PEO (Hb-C) was
      prepared to increase the high molecular weight of Hb. This prevents diffusional
      loss when enclosed in an immunoprotecting membrane. The Hb-C, entrapped in
      microcapsules, enhanced insulin secretion and improved the viability of
      microencapsulated islets by promoting oxygen supply to islets. The introduction
      of the synthetic ECM, crystallized GLP-1, and Hb-C into a BAP may provide a basis
      for designing a compact and rechargeable BAP (macrocapsule).

PMID- 11822820
TI  - Using salivary glands as a tissue target for gene therapeutics.
AB  - Gene transfer offers a potential way to correct local and systemic protein
      deficiency disorders by using genes as drugs, so called gene therapeutics.
      Salivary glands present an interesting target site for gene therapeutic
      applications. Herein, we review proofs of concept achieved for salivary glands
      with in vivo animal models. In that context we discuss problems (general and
      salivary tissue-specific) that limit immediate clinical use for this application
      of gene transfer. Ongoing efforts, however, suggest that salivary glands may be
      suitable as gene therapeutic target sites for drug delivery in the near future.

PMID- 11822821
TI  - Testosterone stimulates growth of tibial epiphyseal growth plate and insulin-like
      growth factor-1 receptor abundance in hypophysectomized and castrated rats.
AB  - Puberty is associated with an increase in the plasma concentration of sex
      steroids, growth hormone (GH), and insulin-like growth factor-1 (IGF-1). Gonadal
      steroid hormones are important for the normal pubertal growth spurt and skeletal
      growth. The mechanism by which gonadal steroids induces skeletal growth is still
      not fully understood. To study the GH-independent effect of testosterone on
      growth, we investigated the effect of testosterone injections on the tibial
      epiphyseal growth plate (EGP) in an in vivo model of hypophysectomized and
      castrated male rats. Four groups (six animals each) of 28-d-old male rats were
      studied. Groups A, B, and C were hypophysectomized and castrated and received 500
      microg/(kg x d) of hydrocortisone and 15 microg/(kg x d) of levothyroxine sodium.
      Groups A and B were also treated with daily sc injections of 10 microg of
      testosterone/100 g of body wt and 100 microg of testosterone/100 g of body wt,
      respectively, for 7 d. Group C was injected with vehicle alone. Group D were
      intact animals injected with saline (controls). Animals were sacrificed on 8 d.
      As expected, serum GH levels were found to be very low (1.13+/-0.1 ng/mL) in the
      hypophysectomized animals (group C, hypopit), and testosterone treatment did not
      change them significantly. Serum IGF-1 decreased from 502.9+/-13 ng/mL in group D
      to 167+/-41.4 ng/mL in group C (p < 0.001). Testosterone therapy had no
      stimulatory effect on serum IGF-1 levels in the hypopit + low-dose group (A)
      (220+/-94.8 ng/mL) and had an inhibitory effect in the hypopit + high-dose group
      (B) (39.3+/-17.5). Histomorphometric determinations demonstrated an EGP width of
      472.3+/-39 microm in the intact animals but only 336.9+/-1.6 microm in the
      hypopit group (C) (p < 0.01). High-dose testosterone treatment (group B)
      significantly increased the EGP width (to 438.8+/-27.8), (p < 0.001), whereas low
      dose testosterone (group A) did not. Immunohistochemistry studies revealed that
      the levels of IGF-1 in the EGP of the control animals were almost negligible and
      that testosterone did not change them. However, testosterone increased in a dose
      dependent manner the abundance of IGF-1 receptor EGP. We conclude that
      testosterone has a direct, local, GH-independent effect on the EGP growth and IGF
      1 receptor abundance.

PMID- 11822822
TI  - Cytochrome P450 aromatase in testis and epididymis of male rhesus monkeys.
AB  - To understand the role of estrogen in testicular and epididymal function of
      rhesus monkeys, we measured steroids in the spermatic and peripheral venus
      circulation and aromatase activity and its mRNA in testis and epididymis.
      Testosterone, estradiol-17beta, and estrone, but not androstenedione, were
      elevated in the spermatic vein serum compared to the peripheral circulation.
      Aromatase activity in testis and in caput epididymis (259+/-16 [SEM] vs 274+/-47
      fmol of 3H2O/mg of protein/h [n = 10], respectively) was significantly higher (p
      < 0.01) than in corpus and cauda (124+/-28 and 113+/-33 fmol of 3H2O/mg of
      protein/h [n = 10], respectively). In the ribonuclease protection assay, two
      P450arom mRNA transcripts were identified in testis and epididymis. One
      corresponded with the aromatase full-length transcript and the other was a
      truncated isoform. The latter was significantly more abundant than the former (p
      < 0.01). Our results demonstrate that the monkey testis and, to a lesser extent,
      the epididymis can aromatize androgens. However, in the epididymis, like in some
      areas of the brain, there was a discrepancy between the aromatase activity and
      the mRNA. The fact that P450arom mRNA and aromatase activity do not correlate in
      the epididymis may indicate that aromatase activity is not strictly regulated at
      the level of RNA expression and that other mechanisms for this regulation should
      be considered.

PMID- 11822823
TI  - Leptin upregulates beta3-integrin expression and interleukin-1beta, upregulates
      leptin and leptin receptor expression in human endometrial epithelial cell
      cultures.
AB  - Human endometrium and endometrial epithelial cells (EECs) either cultured alone
      or cocultured with human embryos express leptin and leptin receptor. This study
      compares the effect of leptin with that of interleukin-1beta (IL-1beta) on the
      expression of beta3-EEC integrin, a marker of endometrial receptivity. Both
      cytokines increased the expression of beta3-EEC at concentrations in the range of
      0.06-3 nM; however, leptin exhibited a significantly greater effect than IL
      1beta. We also determined the regulatory effects of IL-1beta on leptin secretion
      and on the expression of leptin and leptin receptor at the protein level in both
      EEC and endometrial stromal cell (ESC) cultures. In EEC cultures, IL-1beta
      upregulated secretion of leptin and expression of both leptin and leptin
      receptors. No effect of IL-1beta was found in the ESC cultures. However, leptin
      exhibited marginal upregulation of leptin receptor. The upregulation of beta3
      integrin and leptin/leptin receptor expression by IL-1beta in EEC cultures
      indicates that both cytokines may be implicated in embryonic-maternal cross-talk
      during the early phase of human implantation. Our present data also raise the
      possibility that leptin is an endometrial molecular effector of IL-1beta action
      on beta3-integrin upregulation. Thus, a new role for leptin in human reproduction
      as an autocrine/paracrine regulator of endometrial receptivity is proposed.

PMID- 11822825
TI  - Identification and functional analysis of mutations in FAD-binding domain of
      mitochondrial glycerophosphate dehydrogenase in caucasian patients with type 2
      diabetes mellitus.
AB  - Ca2+-responsive mitochondrial FAD-linked glycerophosphate dehydrogenase (mGPDH)
      is a key component of the pancreatic beta-cell glucose-sensing device. The
      purpose of this study was to examine the association of mutations in the cDNA
      coding for the FAD-binding domain of mGPDH and to explore the functional
      consequences of these mutations in vitro. To investigate this association in type
      2 diabetes mellitus, we studied a cohort of 168 patients with type 2 diabetes and
      179 glucose-tolerant control subjects of Spanish Caucasian origin by single
      stranded conformational polymorphism analysis. In vitro site-directed mutagenesis
      was performed in the mGPDH cDNA sequence to reproduce those mutations that
      produce amino acid changes in a patient with type 2 diabetes. We detected
      mutations in the mGPDH FAD-binding domain in a single patient, resulting in a Gly
      to Arg amino acid change at positions 77, 78, and 81 and a Thr to Pro at position
      90. In vitro expression of the mutated constructs in Xenopus oocytes resulted in
      a significantly lower enzymatic activity than in cells expressing the wild-type
      form of the enzyme. Our results indicate that although mutations in the mGPDH
      gene do not appear to have a major role in type 2 diabetes mellitus, the
      reduction in mGPDH enzymatic activity associated with the newly described mGPDH
      mutations suggests that they may contribute to the disease in some patients.

PMID- 11822826
TI  - Preliminary evidence that pharmacologic melatonin treatment decreases rat ghrelin
      levels.
AB  - Ghrelin is a signal peptide isolated from rat stomach antagonistic to actions of
      leptin. Ghrelin stimulates the secretion of growth hormone (GH) and increases
      food intake, body mass, and adiposity in rodents. Photoperiod and melatonin
      regulate leptin secretion of mammals. The aim of the study was to investigate
      possible melatonin-ghrelin interactions in weight regulation by studying the
      effects of continuous pharmacologic melatonin treatment and constant light on
      plasma ghrelin, leptin, and GH levels in rats. Plasma ghrelin concentrations were
      significantly reduced by exogenous melatonin. Ghrelin levels correlated
      negatively with plasma leptin levels in control rats kept in 12 h of light/12 h
      of dark but not in the melatonin-treated animals. The inverse ghrelin-leptin
      relationship was also disrupted by constant illumination. The circulating ghrelin
      and GH levels may not be interrelated in all metabolic situations. The results
      suggest new interplay between the pineal gland and energy metabolism as well as
      reenforce the hypothesis that ghrelin is antagonistic to leptin.

PMID- 11822824
TI  - Impact of acute and chronic ethanol exposure on prolactin in both male and female
      rats.
AB  - The deleterious effects of ethanol (EtOH) on reproduction have been well
      documented. This disruption is usually associated with alterations in prolactin
      (PRL) levels, which is relevant since this hormone is an important participant in
      the reproductive system. Reported EtOH-induced changes in PRL (i.e., stimulation
      or inhibition) have varied. These differences may have been owing to the gender
      or age/sexual maturity of the animal and the mode of the administration of EtOH.
      Therefore, to clarify the impact of EtOH on PRL, a series of experiments were
      conducted utilizing rats of both genders, exposed to EtOH acutely or chronically,
      as adults and as they progressed through puberty. In general, in younger animals
      of both genders, EtOH depressed serum PRL whether given acutely or chronically.
      In adult males, acute EtOH actually stimulated PRL levels while chronic
      administration had no effect. In adult females, EtOH's effect was highly
      dependent on the stage of the estrous cycle in which EtOH was given and during
      which PRL was measured. In conclusion, our studies have shown that the PRL
      response to EtOH is dependent on the gender and age/sexual maturity of the
      animals as well as on the mode of administration.

PMID- 11822827
TI  - Expression of matrix metalloproteinase-2, tissue inhibitors of metalloproteinase
      1, -3 at the implantation site of rhesus monkey during the early stage of
      pregnancy.
AB  - We have examined the expression of MMP-2, TIMP-1, and TIMP-3 mRNA at the
      implantation site of rhesus monkeys during early stage of pregnancy using in situ
      hybridization and Northern blot analysis. The results indicate that MMP-2 mRNA
      was mainly localized in the chorinoic villi and epithelial plaque, suggesting
      that MMP-2 may be involved in the process of epithelial plaque and trophoblast
      invasion. TIMP-3 was specifically expressed in the cells around the spiral
      arteries and maternal-fetal interface. Therefore, TIMP-3 may be the main
      inhibitor that restricts the trophoblast invasion. The TIMP-1 mRNA was detected
      in trophoblast villi and maternal decidua; however, its distribution was not cell
      specific, suggesting a general role in the protection of trophoblast villi and
      maternal decidua from proteolysis by the MMPs secreted by themselves.

PMID- 11822830
TI  - Mapping of genes encoding glycoside hydrolases on the chromosome of Cellulomonas
      fimi.
AB  - Cellulomonas fimi genomic DNA was digested with HpaI, MunI, HindIII, and NsiI,
      producing fragments ranging in size from 20 to 1400 kbp that were resolved by
      pulsed field gel electrophoresis. Genetic and physical linkages were determined
      by Southern blotting and were used to construct a genome map. Cellulomonas fimi
      has a single circular chromosome of approx. 4000 kbp. Except for two closely
      linked genes, cbh6A and cel5A, the genes known to encode glycoside hydrolases are
      scattered widely on the chromosome.

PMID- 11822831
TI  - Root colonization of faba bean (Vicia faba L.) and pea (Pisum sativum L.) by
      Rhizobium leguminosarum bv. viciae in the presence of nitrate-nitrogen.
AB  - There is a lack of knowledge concerning the effect of nitrate-nitrogen (NO3(-)-N)
      at levels known to inhibit nodule formation and functioning on root colonization
      of dinitrogen-fixing legumes. Firstly, this study investigated potential
      differences between Rhizobium leguminosarum bv. viciae 175F9 and its
      bioluminescent-labeled strain 175F9.lux on root colonization of faba bean (Vicia
      faba L.) and pea (Pisum sativum L.). These two strains similarly colonized the
      roots of both hosts. Secondly, this study evaluated the effects of 0 and 10 mol x
      m(-3) NO3(-)-N on root colonization of faba bean and pea by strain 175F9.lux,
      over time. Averaged over both hosts and harvest dates, the presence of NO3(-)-N
      increased the rhizobial population and the root length colonized. In addition,
      our results showed that bioluminescence activity increased from 7 to 14 days
      after sowing and was not correlated to rhizobial population. Finally, to
      demonstrate that an increase in bioluminescence activity was not an indirect
      effect of nitrate on R. leguminosarum bv. viciae 175F9.lux, this study
      investigated the effects of increasing carbon (mannitol) and nitrogen (NO3(-)-N)
      concentrations on the rhizobial population and bioluminescence activity. The
      carbon source was more important than the nitrogen source to increase the
      rhizobial population and bioluminescence activity, which increased with
      increasing mannitol concentration, but not with increasing nitrate concentration.
      Results from this study demonstrated that NO3(-)-N increased rhizobial
      population, especially for faba bean, and the length of root colonized.

PMID- 11822828
TI  - Morphologic and molecular analysis of estrogen-induced pituitary tumorigenesis in
      targeted disruption of transforming growth factor-beta receptor type II and/or
      p27 mice.
AB  - The critical genes and products involved in estrogen-induced tumorigenesis of the
      pituitary gland were investigated in heterozygous transforming growth factor-beta
      (TGF-beta) receptor type II and p27 knockout mouse models. Tgfbr2(+/-), p27(+/-);
      Tgfbr2(+/-), and p27(+/-) mice and C57BL/6J wild-type mice received sc
      implantation of estrogen or placebo pellets for 16 or 25 wk, after which the mice
      were sacrificed and their pituitary glands removed for examination. The
      bromodeoxyuridine labeling indexes in tissue from both the anterior and
      intermediate pituitary lobes from p27 (+/-) and Tgfbr2(+/-); p27(+/-) mice were
      significantly higher than those from wild-type and Tgfbr2(+/-) mice after
      treatment with estrogen for 16 wk. Pituitary tumorigenesis was significantly
      accelerated in Tgfbr2(+/-), p27(+/-), and Tgfbr2(+/-); p27(+/-) mice compared
      with wild-type mice after treatment with estrogen for 16 wk. Pituitary
      tumorigenesis was not accelerated in Tgfbr2(+/-); p27(+/-) mice compared with
      Tgfbr2(+/-) or p27(+/-) mice. Expression of TGF-beta receptor type II mRNA was
      lower in the pituitary gland of Tgfbr2(+/-) mice than in wild-type mice before
      estrogen treatment and was significantly reduced after treatment. Pituitary
      tumorigenesis is accelerated in mice with severe TGF-beta resistance, and greatly
      accelerated in mice with TGF-beta resistance combined with decreased p27
      expression compared with wild-type mice. Both the TGF-beta receptor type II gene
      and p27 gene and their products are involved in estrogen-induced tumorigenesis.

PMID- 11822829
TI  - The endogenous progesterone metabolite, 5a-pregnane-3,20-dione, decreases cell
      substrate attachment, adhesion plaques, vinculin expression, and polymerized F
      actin in MCF-7 breast cancer cells.
AB  - Tumorous human breast tissue readily converts progesterone to 5alpha-pregnane
      3,20-dione (5alphaP), and this metabolite has been shown to stimulate
      proliferation and to decrease adhesion of MCF-7 breast cancer cells. To determine
      the mechanisms of action of 5alphaP on cell adhesion, MCF-7 cells were grown
      without or with 5alphaP (10(-9)-10(-5) M), and the effects on cell and nuclear
      morphology, adhesion plaques, vinculin and actin expression, actin
      polymerization, and microfilament distribution were examined by
      immunohistochemistry, morphometry (using confocal microscopy and digital computer
      imaging analysis), and Western blotting. Treatment of cells with 10(-9)-10(-6) M
      5alphaP resulted in dose-dependent decreases in cell area, cell-to-cell contacts,
      and attachment to the substratum, and increases in variation in nuclear area.
      These changes in the 5alphaP-treated cells were accompanied by decreases in
      vinculin-containing adhesion plaques, vinculin expression, polymerized actin
      stress fibers, and decreases in insoluble and increases in soluble actin
      fractions. The results suggest that the observed decreases in adhesion and
      increases in cell proliferation following 5alphaP treatment may be owing to
      depolymerization of actin and decreased expression of actin and vinculin. We
      conclude that the endogenous progesterone metabolite, 5alphaP, may be involved in
      promoting breast neoplasia and metastasis by affecting adhesion and cytoskeletal
      molecules.

PMID- 11822832
TI  - Structural analyses of the deduced amino acid sequences of a novel type heme
      copper terminal oxidase, cytochrome aco3, from alkalophilic Bacillus YN-2000.
AB  - Cytochrome aco3 from a facultatively alkalophilic bacterium, Bacillus YN-2000,
      was found to be alkaline- and heat-tolerant. To better understand the structural
      features of Bacillus YN-2000 cytochrome aco3, the gene encoding this enzyme was
      cloned and sequenced. Nucleotide sequence analyses of the region neighboring the
      acoI (subunit I) gene revealed that the acoII (subunit II) and acoIII (subunit
      III) genes were concomitantly clustered upstream and downstream of the acoI gene,
      respectively, forming an operon with transcriptional polarity. The deduced amino
      acid sequence of subunit I was highly similar to that of cytochrome caa3 from
      thermophilic bacterium Bacillus PS3 in which the heme a3 could be replaced with
      heme o. Furthermore, a marked paucity of basic amino acid residues was found in
      the cytochrome c-binding subunit II, which might be a result of the adaptation to
      a highly alkaline external milieu.

PMID- 11822833
TI  - Isolation and in vitro cultivation of the aphid pathogenic fungus Entomophthora
      planchoniana.
AB  - Entomophthora planchoniana is an important fungal pathogen of aphids. Although
      Entomophthora chromaphidis has been considered a synonym for E. planchoniana, the
      two species are now separated, and E. planchoniana is reported not to grow in
      vitro. In this paper, we describe for the first time the isolation and
      cultivation of this species. Entomophthora planchoniana was isolated from a
      population of Ovatus crataegarius (Homoptera, Aphididae), which was infected by
      E. planchoniana only. The isolates did not sporulate, but the sequence of the
      small subunit rDNA and the restriction fragment length polymorphism patterns of
      the first part of the large subunit rDNA and the ITS II region confirm that the
      isolates were E. planchoniana. The isolated fungus grew in a medium consisting of
      Grace's insect cell culture medium supplemented with lactalbumin hydrolysate,
      yeastolate, and 10% fetal bovine serum or in GLEN medium with 10% fetal bovine
      serum. Vegetative cells of E. planchoniana were long and club-shaped and did not
      stain with Calcofluor, thus suggesting that they were protoplasts.

PMID- 11822834
TI  - Directed evolution to produce an alkalophilic variant from a Neocallimastix
      patriciarum xylanase.
AB  - The catalytic domain of a xylanase from the anaerobic fungus Neocallimastix
      patriciarum was made more alkalophilic through directed evolution using error
      prone PCR. Transformants expressing the alkalophilic variant xylanases produced
      larger clear zones when overlaid with high pH, xylan-containing agar. Eight amino
      acid substitutions were identified in six selected mutant xylanases. Whereas the
      wild-type xylanase exhibited no activity at pH 8.5, the relative and specific
      activities of the six mutants were higher at pH 8.5 than at pH 6.0. Seven of the
      eight amino acid substitutions were assembled in one enzyme (xyn-CDBFV) by site
      directed mutagenesis. Some or all of the seven mutations exerted positive and
      possibly synergistic effects on the alkalophilicity of the enzyme. The resulting
      composite mutant xylanase retained a greater proportion of its activity than did
      the wild type at pH above 7.0, maintaining 25% of its activity at pH 9.0, and its
      retention of activity at acid pH was no lower than that of the wild type. The
      composite xylanase (xyn-CDBFV) had a relatively high specific activity of 10128
      micromol glucose x min(-1) x (mg protein)(-1) at pH 6.0. It was more thermostable
      at 60 degrees C and alkaline tolerant at pH 10.0 than the wild-type xylanase.
      These properties suggest that the composite mutant xylanase is a promising and
      suitable candidate for paper pulp bio-bleaching.

PMID- 11822835
TI  - Interactions of Pseudomonas aeruginosa PA-IIL lectin with quail egg white
      glycoproteins.
AB  - Pseudomonas aeruginosa produces several lectins, including the galactophilic PA
      IL and the fucose- and mannose-binding PA-IIL. The great advantage of these two
      lectins is their stability in purified preparations. Following observations that
      pigeon egg white blocks Escherichia coli P-fimbriae and PA-IL, we examined the
      interactions of diverse avian egg white components with PA-IIL. This lectin may
      represent both mannose- and fucose-specific microbial adhesins. For comparison,
      Con A (which also binds mannose) and Ulex europaeus lectin (UEA-I, which binds
      fucose) were analyzed in parallel. The lectin interactions with chicken, quail,
      and pigeon egg whites and several purified chicken egg white glycoproteins were
      examined by a hemagglutination inhibition test and Western blotting. Both
      analyses showed that like Con A and unlike UEA-I, which was not sensitive to any
      of these three egg whites, PA-IIL most strongly reacted with the quail egg white.
      However, in contrast with Con A, its interactions with the chicken egg white
      components, excluding avidin, were very poor. The results of this study might
      indicate the possibility that some of the egg white components that interacted
      with the above two mannose-binding lectins (exhibiting individual heterogeneity)
      might be associated with the innate immunity against mannose-specific microbial
      or viral adhesion during the fowl embryonic period.

PMID- 11822836
TI  - Isolation of an esterase-producing Trichosporon brassicae and its catalytic
      performance in kinetic resolution of ketoprofen.
AB  - A yeast strain CGMCC 0574, identified as Trichosporon brassicae, was selected
      from 92 strains for its high (S) selectivity in the hydrolysis of ketoprofen
      ethyl ester. The effective strains of the microorganisms were isolated from soil
      samples with the ester as the sole carbon source. The ethyl ester proved to be
      the best substrate for resolution of ketoprofen among several ketoprofen esters
      examined. The resting cells of CGMCC 0574 could catalyze the hydrolysis of
      ketoprofen ethyl ester with an enantiomeric ratio of 44.9, giving (S)-ketoprofen
      an enantiomeric excess of 91.5% at 42% conversion.

PMID- 11822838
TI  - Osmoregulation in Bacillus subtilis under potassium limitation: a new inducible
      K+-stimulated, VO4(3-)-inhibited ATPase.
AB  - Bacillus subtilis exhibited an inducible K+-transporting ATPase activity with
      apparent Km and maximum velocity Vmax of 12.9 microM and 25.1 micromol x min(-1)
      x (g cell protein)(-1), respectively, when cultivated on a synthetic medium
      containing less than 400 microM K+. Due to this enzyme, the growth rate of the
      bacterium in synthetic medium was not changed down to 115 microM K+, and the
      bacterium was able to grow down to 20 microM K+. The limiting K+ concentration
      was higher in media with osmolarity increased by NaCl or sucrose. The ATPase was
      inhibited by micromolar concentrations of vanadate (Ki = 1.6 microM). The ATPase
      activity was not stimulated by any other monovalent cation. The subunit of this
      ATPase, with an Mr of 52000, covalently bound the gamma phosphate group of ATP.
      This phosphorylated intermediate was unstable in neutral and basic pH as well as
      in the presence of potassium and was stable in acid pH. The enzyme did not show
      immunological cross-reactivity with antibody against Kdp ATPase of Escherichia
      coli.

PMID- 11822837
TI  - DNA-based and culture-based characterization of a hydrocarbon-degrading
      consortium enriched from Arctic soil.
AB  - A hydrocarbon-degrading consortium was enriched from fuel-contaminated soil from
      the northeastern tip of Ellesmere Island (82 degrees 30'N, 62 degrees 19'W). The
      enrichment culture was grown on Jet A-1 fuel at 7 degrees C. Bacterial 16S RNA
      gene (rDNA) fragments were amplified by polymerase chain reaction (PCR) from
      members of the above consortium and cloned into a plasmid vector. Partial
      sequences (approximately 500 bp) were determined for 29 randomly selected rDNA
      clones. The majority of sequences were most similar to the corresponding rDNA
      sequences of Rhodococcus erythropolis (15 sequences), Sphingomonas spp. (six
      sequences), and Pseudomonas synxantha (four sequences). Amplified ribosomal DNA
      restriction analysis confirmed that a larger set of 50 clones had frequencies of
      the three phylotypes similar to those above. Phylotype-specific PCR assays were
      developed and validated for the above three phylotypes. The consortium was plated
      and grown on Jet A-1 fuel vapors, and randomly selected isolated colonies were
      screened with the above PCR assays. Of 17 colonies, six matched the Rhodococcus
      phylotype, and three matched the Pseudomonas phylotype. A representative strain
      of each phylotype was physiologically characterized. Both isolates grew on
      alkanes at low temperature and had general characteristics consistent with their
      respective phylotypes. During growth of the consortium, the three phylotype
      populations were monitored by a most probable number PCR assay. All three
      phylotypes were detected, but their relative abundance was not consistent with
      that of the phylotypes in the clone library. The relative abundance of all three
      phylotypes changed substantially during long-term incubation of the consortium.
      The DNA-based approach used identified phylotypes consistently present in the
      consortium, but it failed to predict the relative abundance of their populations.

PMID- 11822839
TI  - The operon for cytokinin biosynthesis of Erwinia herbicola pv. gypsophilae
      contains two promoters and is plant induced.
AB  - The operon for cytokinin biosynthesis in the gall-forming bacterium Erwinia
      herbicola pv. gypsophilae (Ehg) has been previously shown to reside on an
      indigenous plasmid (pPATH(Ehg)) that is mandatory for pathogenicity. This operon
      consists of two genes: the first open reading frame (pre-etz) is of unknown
      function, whereas the second one (etz) encodes for isopentenyl transferase.
      Northern hybridization performed with the wild-type strain Ehg824-1 grown in
      Luria-Bertani broth demonstrated two transcripts of which an etz-specific
      transcript (1.0 kb) was predominant. Fusion of upstream DNA fragments of both pre
      etz and etz to the ice nucleation reporter gene inaZ in pVSP61 showed high ice
      nucleation activity in both cultures, confirming the presence of two independent
      promoters. An increase of 1-1.5 orders in transcriptional activity of these
      promoters was observed following inoculation of gypsophila cuttings. Mutants of
      Ehg824-1 were generated by insertion of inaZ into pre-etz and etz using the
      transposon reporter Tn3-Spice. An increase of about two orders in transcriptional
      activity was recorded with both mutants following inoculation of gypsophila or
      bean cuttings. A similar induction was also observed when the bacteria were
      applied to the leaf surface of these plants. Unlike other virulence genes present
      on the pPATH(Ehg), neither pre-etz nor etz was regulated by the adjacent hrp gene
      cluster.

PMID- 11822840
TI  - Elemental analysis of uncultured magnetotactic bacteria exposed to heavy metals.
AB  - Natural enrichments of magnetotactic bacteria were used to study the sites where
      heavy metals accumulate in uncultured bacteria. Most bacteria obtained by
      magnetic concentration from these enrichments contained, in addition to the
      magnetosomes, large phosphorus-rich granules in the cytoplasm. Metal (Zn, Mn, Sr,
      Cd, Al, Cr, and Pb) chlorides were added independently to the enrichments, and
      after 24 h, the elemental composition of the phosphorus-rich granules,
      magnetosomes, and "soft parts" (cytoplasm plus cell envelope) of whole bacteria
      was analyzed by energy-dispersive X-ray analysis on a transmission electron
      microscope. All bacteria contained Mn and Sr in the phosphorus-rich granules;
      some of them presented Mn peaks also in the soft parts. Zinc accumulation was
      variable and was found mainly in the phosphorus-rich granules, but also in the
      soft part of some bacteria. Some analyzed bacteria presented Zn peaks only in the
      soft parts, and some of them did not present Zn in any structure. Cadmium and Al
      were found only in the granules of some bacteria. Chromium was found in the soft
      parts of some bacteria. Lead was not detected in any bacteria. We concluded that
      the phosphorus-rich granules are major sites for metal accumulation by these
      bacteria. No conclusive results for magnetosomes were obtained because of the
      limitations of the analytical techniques particularly when used for whole cell
      analysis.

PMID- 11822841
TI  - Peptidases affecting recombinant protein production by Streptomyces lividans.
AB  - The influence of peptidases on human interleukin-3 (rhIL-3) production by a
      recombinant Streptomyces lividans strain was investigated. The bacterium produced
      several general peptidases and tripeptidyl peptidases compromising the
      authenticity of rhIL-3. The level of peptidases depended on growth morphology.
      Growing S. lividans as compact pellets successfully reduced peptidase activity.
      Maximum general peptidase activity in pellet culture was delayed after maximum
      rhIL-3 concentration was achieved. The activity of the tripeptidyl peptidase was
      product (rhIL-3) associated.

PMID- 11822842
TI  - The healthcare reforms of the NHS during the 1990's.

PMID- 11822843
TI  - Early recognition of delirium: review of the literature.
AB  - This review focuses on delirium and early recognition of symptoms by nurses.
      Delirium is a transient organic mental syndrome characterized by disturbances in
      consciousness, thinking and memory. The incidence in older hospitalized patients
      is about 25%. The causes of delirium are multi-factorial; risk factors include
      high age, cognitive impairment and severity of illness. The consequences of
      delirium include high morbidity and mortality, lengthened hospital stay and
      nursing home placement. Delirium develops in a short period and symptoms
      fluctuate, therefore nurses are in a key position to recognize symptoms. Delirium
      is often overlooked or misdiagnosed due to lack of knowledge and awareness in
      nurses and doctors. To improve early recognition of delirium, emphasis should be
      given to terminology, vision and knowledge regarding health in ageing and
      delirium as a potential medical emergency, and to instruments for systematic
      screening of symptoms.

PMID- 11822844
TI  - Integration of lucid individuals and agitated individuals with dementia in
      different care units.
AB  - The purpose of this study was to illuminate how the integration of lucid
      individuals and agitated cognitively impaired individuals affects aspects of
      perceived quality of care. A questionnaire was mailed to hospital wards, nursing
      home wards and residential homes in Sweden. Nursing staff replied to the
      questionnaire on behalf of each care unit. Integration of cognitively impaired
      and lucid patients/residents was identified as a problem, regardless of whether
      the care unit was a hospital ward, nursing home or residential home. Agitated
      behaviours in people who were cognitively impaired could result in lucid
      residents becoming anxious, afraid and irritated. This in turn could lead to an
      exacerbation of behaviour in residents who were already agitated. Sometimes a
      lucid patient/resident was required to share a room with an agitated individual.
      There is a need for staff training specific to the needs of people with dementia.
      Findings suggest that there is a shortage of units designed specifically for the
      care of agitated cognitively impaired patients/residents. The findings of this
      study support the need for healthcare providers in long-term care settings to
      maintain the rights and well being of all patients/residents.

PMID- 11822846
TI  - Relevance of the diagnosis 'stage 1 pressure ulcer': an empirical study of the
      clinical course of stage 1 ulcers in acute care and long-term care hospital
      populations.
AB  - Stage 1 pressure ulcers are difficult to diagnose. Several prevalence studies
      have shown that almost half of the pressure ulcers identified are stage 1. The
      present study investigated the importance of stage 1. The following research
      questions were formulated: Is there a difference between the prevalence of stage
      1 pressure ulcers identified in the institutions participating in the present
      study and that found in the other institutions participating in the Dutch
      National Prevalence Survey? What percentage of stage 1 pressure ulcers are
      reversible within a few hours? What is the clinical course of stage 1 pressure
      ulcers? Which patient characteristics and preventive interventions are related to
      the clinical course of stage 1? The study used a prospective, descriptive and
      comparative design. All patients of six long-term care hospitals and six acute
      care hospitals in whom stage 1 pressure ulcers were identified during the 1999
      National Prevalence Survey in the Netherlands were followed for 1 week (acute
      care hospitals; n = 68 patients) or 2 weeks (long-term care hospitals; n = 115
      patients). The patients were reassessed using the questionnaire developed for the
      National Prevalence Survey (patient characteristics, assessment of risk of
      pressure ulcers, characteristics of the pressure ulcers and use of preventive
      methods) on the same day as the national survey itself, and again after 3 days,
      after 7 days and after 14 days (only long-term care hospitals). The results
      showed fewer stage 1 pressure ulcers in the institutions participating in the
      present study than in the National Prevalence Survey, the difference being almost
      50%. The first reassessment found the prevalence of stage 1 to be further reduced
      by an average of almost 50%, a reduction which was greater for the long-term care
      hospitals than for the acute care hospitals. However, some of the ulcers that had
      disappeared reappeared in subsequent reassessments. In the long-term care
      hospitals, 8.7% of the stage 1 pressure ulcers deteriorated to a higher stage,
      vs. 22.1% in acute care hospitals. No significant patient characteristics were
      found to affect the course of stage 1, except that women in acute care hospitals
      more often had a stage 1 pressure ulcer at the first reassessment than men. In
      general, patients whose stage 1 ulcer deteriorated were undergoing more
      preventive interventions; not all differences were significant. We conclude that,
      although stage 1 is reversible in most cases, it can be interpreted as an
      important warning sign for nurses and patients to act. If no adequate
      interventions are applied, the pressure ulcer may deteriorate.

PMID- 11822845
TI  - Carers' reflections about their video-recorded interactions with patients
      suffering from severe dementia.
AB  - Stimulated recall interviews were used in connection with carers' video-recorded
      interactions with patients suffering from severe dementia before, during and
      after a 1-year intervention involving supervision for individualized nursing
      care. The aim was to illuminate carers' reflections on their everyday life with
      the patients, and to find out if any changes took place across the intervention.
      A phenomenological-hermeneutic approach was used in the analysis, which revealed
      that carers' reflections were focused on the carers themselves, on the patients,
      on context and on the work itself in the shared everyday life. After repeated
      stimulated recall interviews, together with supervision every month, an
      improvement in carers' ability to verbalize their reflections and an awareness
      and knowledge about their own influence on care quality were seen. The
      interdependence between carers and patients made it necessary for the carers to
      cope with many complicated here-and-now situations, and in their reflections the
      carers kept coming back to their efforts to maintain a sense of dignity for the
      patients as well as for themselves. Reflection through stimulated recall seems to
      be an important tool for carers in dementia care to facilitate understanding and
      to help them learn through lived experience, thus developing their skills in
      nursing care.

PMID- 11822847
TI  - The implementation of venous leg ulcer guidelines: process analysis of the
      intervention used in a multi-centre, pragmatic, randomized, controlled trial.
AB  - The production and implementation of clinical practice guidelines is currently a
      high political priority and a rapidly developing field within healthcare in the
      United Kingdom (UK). Their purpose is to provide clinicians with a synthesis of
      the best available external evidence and operationalize the implementation of
      evidence-based practice. Despite indications that clinical guidelines can make a
      difference to the quality of patient care, there is some evidence that
      practitioners struggle with their application. The aim of this paper is to report
      one element of a trial undertaken by three collaborating universities in the
      Northern and Yorkshire Region of the UK health service during 1997-1998. The
      objective was to understand what makes guidelines acceptable and usable, or
      otherwise, to health professionals. The findings reported in this paper describe
      the process of care in those general practices that elected to implement
      guidelines for the management of patients with venous leg ulcers. We conclude
      that planning for training, resource and quality improvement processes must be
      built into a team's guidelines implementation procedures. A preliminary needs
      analysis of the contextual 'hurdles and levers' within each primary healthcare
      team is also necessary to identify individual issues that must be addressed if
      the process is to succeed. These findings provide some lessons for successful
      implementation of clinical guidelines in general. Recommendations for nursing
      policy makers, managers, practitioners and researchers are included.

PMID- 11822848
TI  - Support as a crucial predictor of good compliance of adolescents with a chronic
      disease.
AB  - The purpose of this study was to describe the factors that predict compliance
      among adolescents with a chronic illness. The data were collected by
      questionnaires from adolescents with asthma, epilepsy, juvenile rheumatoid
      arthritis (JRA) and insulin-dependent diabetes mellitus (IDDM). Groups of 300
      adolescents with these illnesses were selected from the Finnish Social Insurance
      Institution's register, giving a total study series of 1200 individuals. The
      final response percentage was 88% (n = 1061). The data were analysed with the
      SPSS software. Logistic regression was used to indicate the predictors of good
      compliance. The compliance of adolescents with a chronic disease was predicted on
      the basis of support from parents, nurses, physicians and friends, as well as
      motivation, energy and willpower. The most powerful predictor was support from
      nurses. The likelihood of adolescents supported by nurses complying with health
      regimens was 7.28-fold compared to the adolescents who did not receive support
      from nurses. The next powerful predictor was energy and willpower. Adolescents
      who had the energy and willpower to take care of themselves complied with health
      regimens with a 6.69-fold likelihood compared to the adolescents who did not have
      energy and willpower. Adolescents who had good motivation were 5.28 times more
      likely to comply than the adolescents who did not have motivation. Support from
      parents, physicians and friends similarly predicted good compliance with health
      regimens.

PMID- 11822849
TI  - Head lice infestation: bug busting vs. traditional treatment.
AB  - The two main methods of managing head lice infestation in the UK are head lice
      lotions and bug busting; there is no conclusive evidence as to which of these
      methods is most effective. The aim of this study was to compare the effectiveness
      of the bug busting method with lotion. A pilot study in the form of a randomized
      controlled trial involving two semi-rural general practices was used. Thirty
      children aged 4-16 years were randomly assigned to two intervention groups. After
      initial dry combing to detect the presence of head lice, one group was treated
      with phenothrin lotion. The bug busting group received combing using special
      combs provided in the bug busting pack and hair conditioner. The main outcome
      measure was the number of adult live lice and nymphs at day 14. On day 14 in the
      bug busting group, total eradication of head lice had occurred in eight children;
      in the lotion group, total eradication had occurred in two children (P=0.052);
      number needed to treat 2.5 (95% CI: 2.19-2.81). These results suggest that bug
      busting performed by nurses in a controlled situation is an effective method of
      managing head lice infestation.

PMID- 11822850
TI  - Promoting a tobacco-free generation: who is responsible for what?
AB  - The aim of the study was to investigate how adolescents, parents and school staff
      look upon different agents' responsibilities in relation to the goal 'a tobacco
      free generation'. This study was part of a larger study and used a descriptive,
      cross-sectional three-group design with questionnaires as the means of data
      collection. The sample comprised 216 pupils in grade five (11 years old) and 225
      pupils in grade eight (14 years old) in a south-western county in Sweden, 293 of
      their parents and 119 school staff (headteachers, teachers, school nurses). All
      respondents agreed that adults should take a clear stand against adolescent
      tobacco use. The adolescents ranked their parents as the number one source of
      tobacco information, while pupils, parents, teachers and headmasters ranked
      school nurses at the bottom rank. The teaching at school focused on risks from
      tobacco use. The non-smoking norm at school was viewed differently by pupils,
      parents and school staff. The actions of family, school and society reflect the
      norms and these do influence adolescent smoking. The conclusion was that the
      responsibility to promote a tobacco-free generation was viewed differently by the
      categories involved in this study. The adolescents put the responsibility mainly
      on parents, while parents put it on the school, and the school staff on special
      health educators. Both parents and school staff need to recognize their
      importance in creating a non-smoking culture. To contribute to the creation of a
      non-smoking generation, school nurses should abandon their passive role in health
      promotion, as shown in this study, and instead engage in encouraging pupils,
      parents and teachers to remain or become tobacco-free.

PMID- 11822851
TI  - Integrating complementary therapies into health care education: a cautious
      approach.
AB  - The movement of complementary therapy training and education into higher
      education in the United Kingdom (UK) and the interest in alternative therapeutic
      approaches within the health professions presents an ideal opportunity for
      multidisciplinary teaching and shared learning. The diversity and similarities of
      complementary therapies and areas of convergence with conventional healthcare
      practice can be explored. The recent publication of the House of Lords Select
      Committee on Science and Technology report on complementary and alternative
      medicine (HL Paper 123) provides a broader context for discussion and makes
      specific recommendations about regulation, education and research in the UK. This
      paper considers the appropriateness of integrating complementary therapies into
      education for conventional healthcare practitioners, what we should integrate,
      and when might be the most appropriate time in the education of healthcare
      practitioners to introduce different therapeutic modalities and their respective
      philosophical languages. Rather than present a range of solutions, the paper
      raises some fundamental issues that are central to the integration of
      complementary therapeutic approaches. If these issues are neglected as we hurry
      to incorporate different 'techniques' into our conventional practice, we may
      simply be left with additional tools that we are ill equipped to use.

PMID- 11822852
TI  - Developing a module for nursing documentation integrated in the electronic
      patient record.
AB  - Norway's regional teaching hospitals are working together on a project to develop
      an interdisciplinary electronic patient record (EPR). This paper presents the
      results of a project to develop nursing documentation as part of an integrated
      EPR to improve the quality and continuity of patient care. The project used a
      consensus process as a working norm. The most important result is that the five
      hospitals have agreed on a framework for nursing documentation, and on the main
      components that need to be implemented in the electronic patient record.

PMID- 11822853
TI  - 'The real stuff': implications for nursing of assessing and measuring a
      terminally ill person's quality of life.
AB  - Two quality of life (QoL) assessment and measurement tools, the Client Generated
      Index (CGI) and the McGill Quality of Life (MQOL) questionnaires, were trialled
      within district nursing palliative care to test usefulness and feasibility for
      holistic intervention selection, individualized palliative care planning, and
      measurement of the quality of dying. The specific focus of this paper is to
      discuss the less tangible outcomes of the trial, which illuminate the partly
      'hidden' value and nature of clinical nursing. These outcomes include awareness
      that the use of such tools may: by actual administration of the tool be, in and
      of itself, a therapeutic nursing action; focus on 'the real stuff from the
      client's perspective, that which matters most to the terminally ill client, but
      may not be classically considered as prompting nursing intervention; and
      facilitate 'the real stuff' of nursing, perhaps known but not usually articulated
      by nurses, and which usually does not feature on care plans nor in time
      allocation schedules.

PMID- 11822854
TI  - The everlasting trial of strength and patience': transitions in home care nursing
      as narrated by patients and family members.
AB  - The aim of this study was to describe and interpret patients' and their family
      members' lived experiences of caring at home. Twelve tape-recorded narratives,
      with seven patients and five family members, were interpreted in accordance with
      a phenomenological-hermeneutic method inspired by Ricoeur. The findings revealed
      life situations where natural caring was changed into patient-care-giver
      relations and the home became a public room. The patients had to deal with
      decreased abilities and the family members with adjusting to caring needs. The
      changes in the life situations were interpreted as long lasting and trying
      transitions. Implications for nursing and further research are proposed.

PMID- 11822855
TI  - Accredited work-based learning (AWBL) for new nursing roles: nurses' experiences
      of two pilot schemes.

PMID- 11822856
TI  - Quality of life 2 years after laparoscopic total fundoplication: a prospective
      study.
AB  - This study was a prospective evaluation of the quality of life of 50 patients
      after laparoscopic total fundoplication surgery for gastroesophageal reflux
      disease. The quality of life of 50 consecutive patients who underwent
      laparoscopic total fundoplication was evaluated using the Gastrointestinal
      Quality of Life Index questionnaire, which included 36 items in five different
      areas: symptoms, physical well-being, psychologic well-being, social
      relationships, and effects of medical treatment. Twenty-seven men and 23 women
      with a mean age of 52.6 +/- 16 years (range, 31-68 years) with gastroesophageal
      reflux disease were treated by laparoscopic total fundoplication (Nissen-Rosetti)
      and were included in the study. The follow-up was at least 2 years after surgery.
      The quality of life was evaluated before the surgery and 1 month, 3 months, 6
      months, 1 year, and 2 years after surgery with follow-up in 100% of the cases. A
      control group of 50 healthy volunteers representing an identical population to
      that of the patients operated on (with respect to age, sex, body mass index,
      profession, and smoking) anonymously completed the same questionnaire. The
      preoperative and postoperative Gastrointestinal Quality of Life Index
      questionnaire scores of patients who had laparoscopic total fundoplication were
      compared with the Gastrointestinal Quality of Life Index questionnaire scores of
      the control group. Before surgery, the Gastrointestinal Quality of Life Index
      questionnaire score (86.7 +/- 8.5) was much inferior to that of the control group
      (123.8 +/- 13.6) (P < 0.001). This score significantly improved 3 months after
      surgery and was comparable (not significant) to that of the healthy control
      population 3 months, 6 months, 1 year, and 2 years after surgery (119.3 +/- 7.8).
      Improvements were reported mainly with respect to gastrointestinal symptoms and
      physical well-being. Social relationships were not modified. The quality of life
      of patients after laparoscopic surgery for gastroesophageal reflux disease
      improved and was close to the level expected in a healthy individual.

PMID- 11822857
TI  - Minilaparoscopic appendectomy.
AB  - The purpose of this study was to evaluate the feasibility of using 2-mm
      laparoscopic instruments in the treatment of appendicitis and to identify risk
      factors that may limit their use. Minilaparoscopic appendectomy was performed
      through a 2-mm port in the umbilicus for a videoendoscope, a 2-mm working port in
      the right upper quadrant, and a 5/12-mm suprapubic port for an endoscopic
      stapler. Minilaparoscopic appendectomy was attempted in 26 consecutive patients
      with appendicitis. Thirty-two consecutive patients undergoing conventional
      laparoscopic appendectomy with 5- and 10-mm instruments and videoendoscopes
      before the availability of 2-mm instrumentation were analyzed for comparison.
      Statistical comparisons were made by the Student t test and Fisher exact test.
      Differences were considered statistically significant at a P value less than
      0.05. There were no conversions to an open appendectomy in the minilaparoscopic
      appendectomy or conventional laparoscopic appendectomy group. The mean operative
      time was 69.5 minutes for the minilaparoscopic appendectomy group and 85.5
      minutes for the conventional laparoscopic appendectomy group (P = 0.02). The mean
      postoperative length of stay was 1.7 days for the minilaparoscopic appendectomy
      group and 2.5 days for the conventional laparoscopic appendectomy group (P =
      0.08). There was no significant difference in the complication rates (P = 0.31).
      Minilaparoscopic appendectomy was completed in 13 (50.0%) patients. Independent
      risk factors (P = 0.05) for conversion to 5- or 10-mm ports were a retrocecal
      appendix and increasing patient age. There were no differences in the mean
      postoperative length of stay (P = 0.12) or complication rate (P = 0.39) between
      the two groups, but mean operative time was longer (P = 0.05) in the converted
      group. Perioperative outcomes for minilaparoscopic appendectomy are comparable to
      those of conventional laparoscopic appendectomy. The use of 2-mm instrumentation
      in the management of appendicitis is limited in patients with retrocecal
      appendicitis. Increasing patient age and a history of abdominal surgery may
      influence the need to convert 2-mm ports to 5- or 10-mm ports.

PMID- 11822859
TI  - Just because you can?

PMID- 11822858
TI  - Transareolar endoscopy-assisted partial mastectomy: a preliminary report of six
      cases.
AB  - Six patients with breast cancer in the upper inner quadrant underwent endoscopy
      assisted partial mastectomy. The tumor was removed with a 2-cm-wide surgical
      margin through a periareolar semicircular incision using a special retractor and
      endoscope system for plastic surgery. Another small incision was made in the
      axilla for total lymph node dissection or sentinel lymph node biopsy. The average
      of total operation time in five patients who underwent partial mastectomy was 241
      minutes (range, 190-315 minutes), and the average time for the procedure of
      partial mastectomy in six cases was 84 minutes (range, 69-113 minutes). The
      cosmetic outcome was excellent. Transareolar endoscopic partial mastectomy can be
      considered as an alternative surgery option and can offer great cosmetic
      advantage for patients with small cancers in the inner quadrants of the breast.

PMID- 11822860
TI  - Pitfalls in thoracoscopic sympathectomy: mechanisms for failure.
AB  - The technical ease of thoracoscopic sympathectomy has established this as the
      procedure of choice for upper-limb sympathectomy. Notwithstanding the invariable
      success of this procedure, those rare instances of unsuccessful sympathectomy are
      disconcerting to the surgeon. Unsuccessful sympathectomy manifests as persistent
      or recurrent sympathetic activity after a seemingly successful procedure. The
      causes of this phenomenon include misinterpretation of the sympathetic chain at
      thoracoscopy, regeneration of the sympathetic chain, and alternate neural
      pathways via the nerve of Kuntz. With the large numbers of sympathectomies being
      undertaken, the few instances of unsuccessful sympathectomy have prompted a
      review of this subject. Although alternate neural pathways may have little
      significance when a T2 ganglionectomy is undertaken, anatomic misinterpretation
      of the sympathetic chain is an important yet under-recognized cause of an
      unsuccessful sympathectomy. Sympathetic nerve regeneration remains extremely
      uncommon. Persistent and recurrent sympathetic activity may be successfully
      managed by resympathectomy performed thoracoscopically.

PMID- 11822861
TI  - The vesical granuloma: rare and late complication of laparoscopic
      cholecystectomy.
AB  - The spillage of gallstones into the peritoneal cavity from iatrogenic perforation
      of the gallbladder that occurs during laparoscopic cholecystectomy can result in
      late and serious complications. We report a case of vesical granuloma with
      symptoms of dysuria, pollakiuria, and vesical tenesmus that occurred 23 months
      after a laparoscopic cholecystectomy. Preoperative diagnostic evaluation showed a
      3-cm vesical neoformation. A partial cystectomy was performed; macroscopic and
      histologic examination documented a central nidus of fragmented gallstones and a
      picture of chronic granulomatous inflammation. Although complications related to
      unretrieved gallstones that spill into the peritoneal cavity during laparoscopic
      cholecystectomy are rare, they are being reported with increasing frequency.
      Therefore, it is important to use tools and techniques that prevent lacerations
      of the gallbladder and involve retrieval of spilled gallstones.

PMID- 11822863
TI  - Spread of a pharyngeal cancer to the abdominal wall after percutaneous endoscopic
      gastrostomy.
AB  - Percutaneous endoscopic gastrostomy is frequently used in patients with head and
      neck cancer to establish enteral access for feeding. Spread of head and neck
      cancer to the gastrostomy site is a rare but increasingly reported complication
      after percutaneous endoscopic placement. We report the 13th such case in the
      literature, occurring in a 51-year-old black man with squamous cell carcinoma of
      the hypopharynx. The mode of tumor spread to the gastrostomy site remains
      debatable. Evidence exists for hematogenous dissemination and direct
      implantation. We think percutaneous endoscopic techniques for enteral access in
      this patient population are contraindicated, and we advocate a laparoscopic
      approach for gastrostomy placement.

PMID- 11822862
TI  - Laparoscopy-assisted distal gastrectomy for gastric malignant lymphoma.
AB  - Although the best treatment for gastric malignant lymphoma remains a
      controversial matter, surgery is the first choice for localized malignant
      lymphoma without lymph node metastasis and invasion to the adjacent organ. We
      report a case of gastric malignant lymphoma that was managed with laparoscopy
      assisted distal gastrectomy. A 47-year-old man was referred to our department for
      management of gastric lymphoma. After preoperative examination revealed a tumor
      confined to the gastric wall but no lymph node metastasis, we performed
      laparoscopy-assisted Billroth I gastrectomy. Histopathologic examination
      confirmed that the tumor was follicular center lymphoma limited to the submucosa
      with no lymph node metastasis. The postoperative course was good. This is the
      first reported case of laparoscopic gastrectomy-treated gastric malignant
      lymphoma. Because it involves minimal access and invasiveness, this procedure may
      be an effective method of treatment of localized malignant lymphoma of the
      stomach.

PMID- 11822864
TI  - Laparoscopic management of a giant adrenal cyst: case report.
AB  - A 22-cm left adrenal cyst in a 30-year-old woman was laparoscopically drained and
      then excised. The main symptom was dull left-upper-quadrant pain. Operative time
      was 95 minutes, and the hospital stay was 1 day. The patient returned to normal
      activity 7 days after surgery. Histology revealed a benign adrenal cyst. At the 3
      month follow-up, ultrasonography showed the absence of any cystic recurrence, and
      adrenal endocrine function was normal. The advantages and disadvantages of this
      modality for the management of adrenal gland cysts are discussed.

PMID- 11822865
TI  - Laparoscopic excision of mesenteric cysts: a report of two cases.
AB  - The authors report two cases of mesenteric cysts that were excised
      laparoscopically. Resection was accomplished with standard minimally invasive
      techniques and use of an ultrasonic scalpel. Both patients recovered promptly
      with minimal morbidity and returned to full activity within a short time. This
      reveals the suitability of minimally invasive surgery for this particular disease
      process.

PMID- 11822867
TI  - Involvement of Rho GTPases and their effectors in the secretory process of PC12
      cells.
AB  - We investigated the involvement of Rho GTPases in the secretory process of PC12
      cells. Overexpression of wild-type RhoA, Rac1, or Cdc42 did affect exocytosis. In
      contrast, secretion elicited by depolarizing K(+) concentrations was enhanced by
      the dominant negative mutants RhoA(N19), Rac1(N17), and Cdc42(N17) and was
      diminished by the constitutively active mutants RhoA(V14), Rac1(V12), and
      Cdc42(V12). The inhibition observed in the presence of RhoA(V14) was likely a
      result of the activation of ROK(alpha), since the catalytic domain of this kinase
      was able to mimic both the reorganization of the actin cytoskeleton and the
      decrease in exocytosis induced by the RhoA mutant. Part of the effect of
      Rac1(V12) may be due to POR1 activation. Thus, overexpression of full-length POR1
      diminished K(+)-stimulated exocytosis, and a point mutation in the effector
      domain of Rac1(V12) that prevents the interaction with POR1 abolished the
      inhibitory effect of the GTPase. We also searched for the Cdc42(V12) target but
      overexpression of the Cdc42 effector WASP did not mimic the inhibition of
      exocytosis observed in cells transfected with the activated GTPase. Our findings
      indicate that different signaling cascades resulting in the activation of RhoA,
      Rac1, or Cdc42 can modulate the exocytotic process of neuroendocrine cells.

PMID- 11822866
TI  - Thoracoscopically managed parathyroid adenoma in the upper anterior mediastinum.
AB  - We thoracoscopically managed parathyroid adenoma of the upper anterior
      mediastinum in a 29-year-old man. He had a backache and was found to have
      bilateral ureteric stones, hypercalcemia, and extremely increased parathyroid
      hormone levels. 99mTc-methoxyisobutyl isonitrile scintigraphy showed an
      accumulation area projected onto the right thyroid lobe and the upper
      mediastinum. A diagnosis of primary hyperparathyroidism secondary to double
      adenomas was made. The patient then underwent surgical intervention. With the
      patient under general anesthesia with one-lung ventilation, a reddish brown
      adenoma of an upper mediastinum was removed thoracoscopically with three trocars,
      whereas the right superior parathyroid adenoma was excised by a standard open
      cervical procedure. Conventionally, the mediastinal parathyroid adenoma was
      removed by an open approach and was associated with perioperative distress to the
      patient. If the exact location of the mediastinal lesion is established,
      thoracoscopic excision of these lesions is feasible and is strongly recommended.

PMID- 11822868
TI  - Identification of a candidate tumor-suppressor gene specifically activated during
      Ras-induced senescence.
AB  - Normal cells display protective responses against oncogenes. Notably, oncogenic
      Ras triggers an irreversible proliferation arrest that is reminiscent of
      replicative senescence and that is considered a relevant tumor-suppressor
      mechanism. Here, we have used microarrayed filters to identify genes specifically
      upregulated in Ras-senescent human fibroblasts. Among the initial set of genes
      selected from the microarrays, we found the cell-cycle inhibitor p21(Cip1/Waf1),
      thus validating the potency of the screening to identify markers and mediators of
      Ras-senescence. A group of six genes, formed by those more highly upregulated
      during Ras-senescence, was analyzed in further detail to evaluate their
      specificity. In particular, we examined their expression in cells overexpressing
      Ras but rendered resistant to Ras-senescence by the viral oncoprotein E1a; also,
      we have studied their expression during replicative senescence, organismal aging,
      H(2)O(2)-induced senescence, and DNA damage. In this manner, we have identified a
      novel gene, RIS1 (for Ras-induced senescence 1), which is not upregulated in
      association to any of the above-mentioned processes, but exclusively during Ras
      senescence. Furthermore, RIS1 is also upregulated by the transcriptional factor
      Ets2, which is a known mediator of Ras-induced senescence. Interestingly, RIS1 is
      located at chromosomal position 3p21.3 and, more specifically, it is included in
      a short segment of just 1 Mb previously defined by other investigators for its
      tumor-suppressor activity. In summary, we report the identification of a novel
      gene, RIS1, as a highly specific marker of Ras-induced senescence and a candidate
      tumor-suppressor gene.

PMID- 11822869
TI  - Inhibitors of farnesyl protein transferase and MEK1,2 induce apoptosis in
      fibroblasts transformed with farnesylated but not geranylgeranylated H-Ras.
AB  - Farnesyl protein transferase inhibitors (FTIs) reverse the transformed phenotype
      of fibroblasts expressing activated H-Ras and block anchorage-independent growth
      and tumorigenesis of tumor cell lines independent of their Ras mutational status.
      FTIs induce significant tumor regression accompanied by apoptosis in several
      transgenic mouse tumor models. FTI treatment of tumor cells in vitro is
      proapoptotic under certain cell culture conditions. Induction of apoptosis by
      FTIs in vitro generally requires a second death-promoting signal. To better
      understand FTI-induced apoptosis we analyzed the effect of SCH 66336, a tricyclic
      FTI, on apoptosis of Ras-transformed Rat2 fibroblasts. Treatment of H-Ras-CVLS
      transformed fibroblasts with MEK1,2 inhibitors provides a pharmacological second
      signal to enhance FTI-induced apoptosis. Simultaneous treatment of these cells
      with a MEK1,2 inhibitor markedly enhanced caspase-3 activity and the apoptotic
      response to SCH 66336. The combination treatment resulted in a more complete and
      sustained inhibition of MAPK pathway activity than observed with either drug
      alone. Surprisingly, after treatment with either agent alone or in combination,
      no apoptotic response was observed in Rat2 cells transformed with a
      geranylgeranylated form of H-Ras (H-Ras-CVLL). Differences were also observed
      when SCH 66336 treatment was combined with forced suspension growth or serum
      withdrawal, in that an increase in drug-induced apoptosis was observed in H-Ras
      CVLS-transformed Rat2 cells but not H-Ras-CVLL-transformed Rat2 cells. The lack
      of apoptotic effect of SCH 66336 and MEK inhibitor, alone or in combination, in H
      Ras-CVLL-transformed cells suggests a difference in the reliance of cells
      transformed with farnesylated and geranylgeranylated forms of H-Ras on the MAPK
      signal transduction cascade for survival. K-Ras-transformed cells underwent
      apoptosis upon MEK1,2 inhibition but not in response to SCH 66336 treatment. The
      apoptotic response induced by MEK1,2 inhibitors is much greater in magnitude in H
      Ras-transformed cells than in K-Ras-transformed cells, also pointing to
      differences in pathway utilization and/or dependence for these two Ras isoforms.

PMID- 11822870
TI  - Growth-related signaling regulates activation of telomerase in regenerating
      hepatocytes.
AB  - Although there have been many reports on the relationship between activation of
      telomerase and carcinogenesis, the role of telomerase in normal cellular growth
      is still unclear. In this study, we analyzed the relationship between
      upregulation of telomerase activity and cell cycle progression during the liver
      regeneration process by using an in vivo mouse two-thirds partial hepatectomy
      (PH) model as well as by using in vitro hepatocyte culture systems. Furthermore,
      we also investigated the effects of growth factors on telomerase activity during
      liver regeneration and the influence of MAPK pathway inhibitors (MEK inhibitors
      PD98059 and U0126; p38 MAPK inhibitor SB203580) on the telomerase activity of
      regenerating hepatocytes in vitro. An upregulation of the telomerase activity was
      found at 24 h after PH, and thereafter an increase in the S-phase fraction was
      observed at 36-48 h. There was no remarkable change in the telomere length after
      PH. Preoperative treatment with EGF and HGF increased the in vivo telomerase
      activity. In a hepatocyte primary culture, the upregulation of the telomerase
      activity required the presence of EGF, and this upregulation was accelerated by
      the addition of HGF. A remarkable activation of p44/42 MAPK was seen but no such
      activation of p38 MAPK was observed at 48 h after PH. Although SB203580 had no
      effect on the telomerase activity of regenerating hepatocytes, treatment with MEK
      inhibitors (PD 98059, U0126) significantly repressed the telomerase activity. In
      conclusion, the telomerase activity is upregulated before hepatocytes enter the S
      phase, and both EGF and HGF play important roles in this step. In addition, the
      activation of the p44/42 MAPK pathway seems to play an essential role in
      telomerase upregulation during the liver regeneration process.

PMID- 11822871
TI  - Acid sphingomyelinase activation requires caspase-8 but not p53 nor reactive
      oxygen species during Fas-induced apoptosis in human glioma cells.
AB  - During apoptosis of human glioma cells induced by anti-Fas antibody, ceramide
      formation with activation of acid, but not neutral sphingomyelinase (SMase), was
      observed. A potent inhibitor of acid SMase, SR33557, effectively inhibited
      ceramide formation and apoptosis. Fas-induced apoptosis and ceramide formation
      proceeded regardless of p53 status. The agents, which modify intracellular levels
      of reactive oxygen species (ROS) and reduced glutathione (GSH), failed to
      modulate Fas-induced acid SMase activation and apoptosis. Moreover, expression of
      functional p53 protein using a temperature-sensitive human p53val(138) induced
      ceramide generation by activation of neutral SMase but not acid SMase through ROS
      formation. Peptide inhibitors for caspases-8 (z-IETD-fmk) and -3 (z-DEVD-fmk)
      suppressed Fas-induced apoptosis. However, activation of acid SMase was inhibited
      only by z-IETD-fmk. Thus, ceramide generated by acid SMase may take a part in Fas
      induced apoptosis of human glioma cells and acid SMase activation may be
      dependent on caspase-8 activation, but not on p53 nor ROS.

PMID- 11822872
TI  - Fibronectin promotes cell cycle entry in smooth muscle cells in primary culture.
AB  - Smooth muscle cell proliferation after arterial injury is regulated by growth
      factors and components of the extracellular matrix. We have previously
      demonstrated that fibronectin promotes a phenotypic modulation of freshly
      isolated rat smooth muscle cells from a contractile to a synthetic phenotype in
      primary culture and supports the ability of the cells to respond to growth
      factors. Here, we analyzed if fibronectin promotes cell cycle entry in freshly
      isolated rat aortic smooth muscle cells during primary culture. Cell cycle
      analysis showed that cells seeded on fibronectin remained in the G(0)/G(1) phase
      of the cell cycle during the first 6 days of culture. During this period, there
      was an increased expression of cyclin D1 and p27(KIP1) in the absence of
      exogenous growth factors. Addition of serum was followed by enhanced cyclin D1
      expression, decreased p27(KIP1) levels, hyperphosphorylation of Rb protein,
      induction of cyclin A and cyclin D3 expression, and cell cycle progression into S
      phase. The results indicate that fibronectin initiates cell cycle entry in
      freshly isolated smooth muscle cells by promoting the induction of cyclin D1 and
      thereby facilitates further cell cycle progression together with growth factors.

PMID- 11822873
TI  - Role of the membrane-proximal O-glycosylation site in sorting of the human
      receptor for neurotrophins to the apical membrane of MDCK cells.
AB  - We have analyzed the respective roles of the stalk and/or the O-glycosylation
      sites in apical sorting by producing partially deleted mutants in this region of
      the human receptor for neurotrophins (P75(NTR)). The mere presence of O
      glycosylations was not sufficient for efficient delivery to the apical surface
      since changing the stalk domain of P75(NTR) for the heavily O-glycosylated stalk
      from human decay-accelerating factor led to random distribution of the chimera.
      The presence of O-glycosylations, however, was a prerequisite for exit from the
      ER and protection from intracellular cleavage since a P75(NTR) containing the non
      O-glycosylated stalk of the human placental alkaline phosphatase was not
      transported to the cell surface but was cleaved and secreted from the basolateral
      side. Deletion of the membrane-proximal part of the stalk showed a more dramatic
      reversal of polarity of P75(NTR) than the deletion of the distal part.
      Furthermore, moving the first putative O-glycosylation site (T216) two amino
      acids away from the membrane resulted in a loss of apical polarity of P75(NTR),
      suggesting that an important clue for apical sorting resides in this part of the
      stalk. This loss of apical polarity paralleled a loss of association of P75(NTR)
      mutants with Lubrol rafts. These data indicate that the position of O-glycans in
      the proximal part of the stalk domain of P75(NTR) is crucial for apical sorting
      and may regulate association with apical rafts.

PMID- 11822874
TI  - Characterization of ThOX proteins as components of the thyroid H(2)O(2)
      generating system.
AB  - We have recently cloned two thyroid-specific cDNAs encoding new members of the
      NADPH oxidase family. ThOX1 and ThOX2 proteins are colocalized with
      thyroperoxidase at the apical membrane of human thyroid cells. In the present
      study we have determined their subcellular localization and maturation in
      relation to their enzymatic activity. A majority of ThOX proteins accumulated
      inside the cell and only a small fraction was expressed at the surface. Western
      blots demonstrated that ThOX's are glycoproteins of 180,000 and 190,000. When
      totally deglycosylated the molecular weight of both ThOX1 and ThOX2 drops to
      160,000. Ca(2+) stimulates the basal H(2)O(2) generation in PC Cl3 cells at a
      level corresponding to 20% of the leukocyte H(2)O(2) production stimulated by
      PMA. Nonthyroid cell lines transfected with ThOX1 and ThOX2 show only a single
      immunoreactive band in Western blot analysis, corresponding to the protein of
      180,000. This "immature" protein remains exclusively intracellular and does not
      present any enzymatic activity. This is not modified by coexpression of
      thyroperoxidase and p22(Phox). Transfection of ThOX cDNAs into PLB-XCGD cells
      does not reconstitute their NADPH oxidase activity. We conclude that (1) the
      thyroid contains some elements of the leukocyte H(2)O(2)-generating system but
      not all of them; (2) ThOX's are predominantly or exclusively located inside the
      cell in thyrocytes or in transfected cells, respectively, and as such they are
      inactive; (3) ThOX's cannot replace gp91(Phox) in the leukocyte; and (4) the
      thyroid H(2)O(2)-generating system is analogous to the leukocyte system with
      regard to ThOX's and gp91(Phox) but very different in other aspects. Additional
      thyroid-specific components are probably required to get complete protein
      processing and full enzymatic activity in the thyroid.

PMID- 11822875
TI  - AP-1 transcription factor complex is a target of signals from both WnT-7a and N
      cadherin-dependent cell-cell adhesion complex during the regulation of limb
      mesenchymal chondrogenesis.
AB  - Wnt signaling has been implicated in the regulation of limb mesenchymal
      chondrogenesis. In this study, we have analyzed the molecular mechanism of Wnt-7a
      inhibition of chondrogenic differentiation by examining the involvement of
      mitogen-activated protein kinase (MAPK) pathways, i.e., Erk and p38. The
      combination of Wnt-7a misexpression and Erk inhibition partially recovers Wnt-7a
      inhibition of chondrogenic differentiation, whereas the combination of Wnt-7a
      misexpression and p38 inhibition acts in a synergistic chondro-inhibitory
      fashion. Although Wnt-7a misexpression has no direct effect on Erk signaling, it
      increases the activity of one of the ultimate targets of the MAPK pathway, c-jun,
      a major component of the activator protein-1 (AP-1) transcription factor complex.
      In addition, Wnt-7a misexpression enhances the activity of an AP-1 promoter
      luciferase reporter construct by approximately 2.3-fold in vitro. Interestingly,
      misexpression of wild-type N-cadherin in these micromass cultures suppresses the
      activity of the same AP-1 promoter by approximately 40%, whereas misexpression of
      an extracellular 390-amino-acid N-terminal deletion mutant of N-cadherin has a
      stimulatory effect on the AP-1 promoter activity by approximately 2.6-fold. Thus,
      our results suggest that at least a part of the chondro-inhibitory effect of Wnt
      7a misexpression may involve AP-1 transcription factor stimulation. Furthermore,
      a very tightly regulated level of AP-1 activity is necessary for the process of
      limb mesenchymal chondrogenesis, and signals from Wnt-ligands (e.g., Wnt-7a),
      cell adhesion molecules (e.g., N-cadherin), and MAPK pathways (e.g., Erk and p38)
      are interactively involved in this regulation.

PMID- 11822876
TI  - Targeted disruption of nebulette protein expression alters cardiac myofibril
      assembly and function.
AB  - To evaluate nebulette's role in cardiac myofibrils, cardiomyocytes expressing
      green fluorescent protein (GFP)-nebulette constructs were monitored for their
      ability to contract and myofilament protein distribution was analyzed. Cells
      expressing full-length GFP-nebulette appear unaffected and exhibit normal beating
      frequencies. Expression of the GFP linker and SH3 results in loss of the
      endogenous nebulette and tropomyosin; however, Z-line and thick filaments are
      undisturbed. Cells expressing either of these domains have dramatically reduced
      beating frequencies, consistent with the loss of thin filament proteins. This
      loss was inhibited by the addition of protease inhibitors during culturing. The
      GFP repeat domain disrupts both myofibrillogenesis and contraction in spreading
      cardiomyocytes, whereas introduction of this protein into well-spread
      cardiomyocytes results in localization at the Z-line and a 50% reduction in
      beating frequency. Ultimately, these cells form bundles containing the GFP repeat
      and many myofilament proteins. Interestingly, butanedione monoxime inhibition of
      contraction inhibited the formation of these bundles. These results show that the
      GFP-nebulette domains have a dominant-negative effect on the distribution and
      function of the sarcomeric proteins. Taken together with the observation that
      nebulette colocalizes with alpha-actinin in the pre-, nascent, and mature
      myofibrils, our data demonstrate the importance of this cardiac-specific nebulin
      isoform in myofibril organization and function.

PMID- 11822877
TI  - An important role for protein kinase C-delta in human keratinocyte migration on
      dermal collagen.
AB  - Migration of human keratinocytes plays a critical role in the re
      epithelialization of human skin wounds, the process by which the wound bed is
      resurfaced and closed by keratinocytes as it forms a new epidermis. While the
      importance of ECM components and serum factors in the regulation of keratinocytes
      motility is well established, the intracellular signaling mechanisms remain
      fragmentary. In this study, we investigated the role of protein kinase Cdelta
      (PKCdelta) signaling in the promotion of human keratinocyte migration by a
      collagen matrix and bovine pituitary extract. We found that pharmacological
      inhibition of the PKCdelta pathway completely blocks migration. Using a
      lentivirus-based vector system, which offers more than 90% gene transduction
      efficiency to human keratinocytes, we show that the kinase-defective mutant of
      PKCdelta (K376R) dramatically inhibits human keratinocyte migration. Furthermore,
      PKCdelta is activated in migrating human keratinocytes. These observations
      indicate for the first time that the PKCdelta pathway plays an important role in
      the control of human keratinocyte migration.

PMID- 11822878
TI  - Suppression of human melanoma metastasis by the metastasis suppressor gene,
      BRMS1.
AB  - We recently identified a novel metastasis suppressor gene, BRMS1, in breast
      cancer. Since the BRMS1 gene maps to chromosome 11q13.1-q13.2 and since
      chromosome 11q defects have been described in various stages of human melanoma
      progression, we hypothesized that BRMS1 may function as a tumor or metastasis
      suppressor in melanomas as well. Quantitative real-time RT-PCR revealed that
      BRMS1 mRNA expression was high in melanocytes, considerably reduced in early
      melanoma-derived cell lines, and barely detectable in advanced/metastatic cell
      lines. Stable transfectants of BRMS1 in the human melanoma cell lines MelJuSo and
      C8161.9 did not alter the tumorigenicity of either cell line, but significantly
      suppressed metastasis compared to vector-only transfectants. Orthotopic tumors
      continued to express BRMS1, but expression was lost in lung metastases. In vitro
      morphology, growth rate, and histology of BRMS1 transfectants were similar to
      controls. BRMS1 transfectants were less invasive in a collagen sandwich assay and
      had restored homotypic gap junctional intercellular communication (GJIC). Thus,
      BRMS1 functions as a metastasis suppressor in more than one tumor type (i.e.,
      breast carcinoma and cutaneous melanoma) by modifying several metastasis
      associated phenotypes.

PMID- 11822879
TI  - Regulation of VE-cadherin linkage to the cytoskeleton in endothelial cells
      exposed to fluid shear stress.
AB  - Endothelial cells exposed to shear stress realigned and elongated in the
      direction of flow through the coordinated remodeling of their adherens junctions
      and actin cytoskeleton. The elaborate networks of VE-cadherin complexes in static
      cultures became more uniform and compact in response to shear. In contrast, the
      cortical actin present in static cultures was reorganized into numerous stress
      fiber bundles distributed parallel to the direction of flow. Exposure to shear
      did not significantly alter the expression of the junctional proteins VE
      cadherin, beta-catenin, and alpha-catenin, but the composition of the junctional
      complexes did change. We detected a marked decrease in the alpha-catenin
      associated with VE-cadherin complexes in endothelial monolayers subjected to
      shear. This loss of alpha-catenin, the protein that links beta-catenin-bound
      cadherin to the actin cytoskeleton, was not due to decreased quantities of beta
      catenin associated with VE-cadherin. Instead, the loss of alpha-catenin from the
      junctional complexes coincided with the increased tyrosine phosphorylation of
      beta-catenin associated with VE-cadherin. The change in beta-catenin
      phosphorylation closely correlated with the shear-induced loss of the protein
      tyrosine phosphatase SHP-2 from VE-cadherin complexes. Thus, the functional
      interaction of alpha-catenin with VE-cadherin-bound beta-catenin is regulated by
      the extent of tyrosine phosphorylation of beta-catenin. This, concomitantly, is
      regulated by SHP-2 associated with VE-cadherin complexes.

PMID- 11822880
TI  - Transforming growth factor beta stimulates fibroblast-collagen matrix contraction
      by different mechanisms in mechanically loaded and unloaded matrices.
AB  - Studies were carried out to test the idea that transforming growth factor beta
      (TGFbeta) stimulated fibroblast contraction of collagen matrices by different
      mechanisms depending on mechanical loading on the cells and matrix. Under
      mechanically unloaded conditions (floating matrices), TGFbeta stimulated
      contraction directly as an agonist and indirectly by preactivating cells to
      express the myofibroblast phenotype. Increased contraction of floating matrices
      by preactivated cells appeared to result in part from an autocrine mechanism.
      Under mechanically loaded conditions (stressed matrices), TGFbeta had no direct
      agonist effect on contraction. Fibroblasts preactivated to become myofibroblasts
      showed increased ability to transfer tension to stressed matrices, and tension
      persisted even after the cells' actin cytoskeleton was disrupted. Our findings
      are consistent with the idea that fibroblasts activated to become myofibroblasts
      in vitro have increased contractile activity and indicate that multiple
      mechanisms that differ depending on mechanical loading on the cells and matrix
      are involved.

PMID- 11822881
TI  - Expression level of c-FLIP versus Fas determines susceptibility to Fas ligand
      induced cell death in murine thymoma EL-4 cells.
AB  - The caspase-8 inhibitor c-FLIP blocks death receptor-mediated cell death and
      plays an essential role in the regulation of lymphocyte homeostasis and the
      immune escape of tumors. The murine thymoma cell line EL-4 was resistant to Fas
      ligand (FasL)-induced apoptosis by constitutive expression of FLIP (L).
      Cycloheximide downregulated the expression of FLIP (L) and markedly sensitized EL
      4 cells to FasL-induced apoptosis. In contrast, DNA-damaging agents sensitized EL
      4 cells to FasL-induced cell death via an increase of cell-surface Fas without
      any influence on FLIP (L) expression. Enforced expression of transfected Fas
      rendered EL-4 cells highly susceptible to FasL-induced cell death. These findings
      demonstrate that susceptibility to FasL-induced cell death mainly depends on the
      expression level of c-FLIP versus cell-surface Fas.

PMID- 11822882
TI  - Time course of the development of Alzheimer-like pathology in the doubly
      transgenic PS1+APP mouse.
AB  - Doubly transgenic mice expressing both a mutated amyloid precursor protein and a
      mutated presenilin-1 protein accumulate A(beta) deposits as they age. The early
      A(beta) deposits were found to be primarily composed of fibrillar A(beta) and
      resembled compact amyloid plaques. As the mice aged, nonfibrillar A(beta)
      deposits increased in number and spread to regions not typically associated with
      amyloid plaques in Alzheimer's disease. The fibrillar, amyloid-containing
      deposits remained restricted to cortical and hippocampal structures and did not
      increase substantially beyond the 12-month time point. Even at early time points,
      the fibrillar deposits were associated with dystrophic neurites and activated
      astrocytes expressing elevated levels of glial fibrillary acidic protein.
      Microglia similarly demonstrated increased staining for complement receptor-3 in
      the vicinity of A(beta) deposits at early time points. However, when MHC-II
      staining was used to assess the degree of microglial activation, full activation
      was not detected until mice were 12 months or older. Overall, the regional
      pattern of A(beta) staining resembles that found in Alzheimer disease; however, a
      progression from diffuse A(beta) to more compact amyloid deposits is not observed
      in the mouse model. It is noted that the activation of microglia at 12 months is
      coincident with the apparent stabilization of fibrillar A(beta) deposits, raising
      the possibility that activated microglia might clear fibrillar A(beta) deposits
      at a rate similar to their rate of formation, thereby establishing a relatively
      steady-state level of amyloid-containing deposits.

PMID- 11822883
TI  - The effects of long-term treatment with metrifonate, a cholinesterase inhibitor,
      on cholinergic activity, amyloid pathology, and cognitive function in APP and PS1
      doubly transgenic mice.
AB  - Recent studies in cell cultures have shown that modulating the cholinergic
      activity can influence the processing and metabolism of amyloid precursor protein
      (APP). To investigate whether acetylcholinesterase inhibitors (ChEIs) could
      decrease production of amyloid beta-peptide (A(beta)) and slow down the
      accumulation of A(beta) also in vivo, we chronically administered metrifonate
      (100 mg/kg, po), a second-generation ChEI, to 7-month-old doubly transgenic
      APP+PS1 mice and their nontransgenic littermate controls for 7 months. Behavioral
      studies, including open field test, T maze, and water maze, were conducted after
      6 months treatment with metrifonate, and the mice were sacrificed at the age of
      14 months for biochemical and histological analyses. The long-term treatment with
      metrifonate failed to inhibit the marked overproduction and deposition of A(beta)
      in the APP+PS1 mice; in contrast, it increased both A(beta)40 and A(beta)42
      levels in the hippocampus. However, the A(beta)42 to 40 ratio was significantly
      reduced by the treatment. In addition, the number of amyloid plaques in the
      hippocampus did not differ between the treatment and the control groups.
      Tolerance to cholinesterase inhibition might be induced in the mouse brain
      because the inhibition rate of AChE was attenuated from about 80 to 50% during
      the experiment in both APP+PS1 and nontransgenic mice. The metrifonate treatment
      did not affect cognitive testing parameters but reduced swimming speed and
      locomotor activity in both genotypes. Our results do not support the idea that
      ChEIs would slow down the progression of amyloid pathology in Alzheimer's
      disease.

PMID- 11822884
TI  - Target-specific innervation of embryonic cerebellar transplants by regenerating
      olivocerebellar axons in the adult rat.
AB  - The reestablishment of topographically organized connections is a necessary
      prerequisite to obtain a full anatomical repair following brain injury. One
      system where such an issue can be addressed is the olivocerebellar system, where,
      normally, clusters of inferior olive neurons project to neurochemically
      heterogeneous Purkinje cell compartments defined by the expression of cell
      specific markers, such as zebrin II. To assess whether adult injured
      olivocerebellar axons that regenerate into cerebellar transplants are able to
      establish target-specific innervation of grafted Purkinje cells, we made surgical
      transections in the white matter of adult rat cerebella and placed solid grafts
      from the embryonic cerebellar anlage into the lesion site. The transplanted
      tissue developed highly organized minicerebella, in which Purkinje cells were
      distributed into distinct clusters of zebrin II-immunopositive or -immunonegative
      neurons, mimicking the cortical compartments present in the normal adult
      cerebellum. Olivocerebellar axons, labeled by biotinylated dextran amine tracing,
      regenerated into the transplants where they formed discrete patches made of
      several terminal arbors impinging upon Purkinje cell dendrites. Among 401 such
      climbing fiber patches, 96% exclusively innervated Purkinje cells of either
      phenotype and stopped at the border of the zebrin II(+/-) Purkinje cell clusters,
      whereas only 4% were extended across this boundary and innervated both zebrin II
      positive and -negative Purkinje cells. The results obtained support the view that
      the embryonic cerebellar tissue provides target-specific information that can be
      decoded by ingrowing adult olivocerebellar axons in order to establish
      appropriate innervation patterns with zebrin II-positive or -negative Purkinje
      cell compartments.

PMID- 11822885
TI  - Effect of allogeneic Schwann cell transplantation on peripheral nerve
      regeneration.
AB  - Transplantation of allogeneic Schwann cells (SC) would make it feasible to
      reconstruct immediately peripheral nerve defects, compared to using autologous
      SC; however, this treatment modality has not been adequately evaluated. The aim
      of this study was to characterize and compare the effects of allogeneic versus
      syngeneic SC transplantation following peripheral nerve injury.
      Polyhydroxybutyrate conduits were used to bridge a 10-mm gap in the rat sciatic
      nerve. The conduits were filled with alginate hydrogel with or without cultured
      allogeneic or syngeneic genetically labeled SC, without the use of
      immunosuppressive therapy, and examined after 2, 3, and 6 weeks with 5-bromo-4
      chloro-3-indoyl-beta-D-galactosidase chemical staining and immunohistochemistry
      to quantify SC migration into the conduit, axonal regeneration, the state of SC
      differentiation, and the expression of major histocompatibility complexes (MHC) I
      and II, as well as to quantify macrophage and B- and T-lymphocyte infiltration.
      Allogeneic SC were rejected by 6 weeks, whereas syngeneic SC could still be
      identified. Allogeneic and syngeneic SC equally enhanced the axonal regeneration
      distance but the quantity of axons was greater using syngeneic SC. The ingrowth
      of SC into the conduits containing allogeneic SC was similar to that observed in
      the presence of syngeneic SC, indicating the absence of deleterious immune
      response. SC continued to express phenotypic markers of nonmyelination and these
      were highest in conduits with allogeneic SC. Expression of MHC I and II was
      higher in the conduits with allogeneic SC at 3 weeks and without significant
      difference in the number of macrophages and lymphocytes, except at 6 weeks, when
      there was a larger number of lymphocytes using syngeneic SC. In conclusion,
      allogeneic SC enhanced axonal regeneration distance and did not induce a
      deleterious immune response. In a clinical setting the immediate availability of
      allogeneic SC for transplantation may compensate for the better outcome achieved
      by the use of autologous SC that require a longer preparation time in culture.

PMID- 11822886
TI  - Neuroprotective effects of ginseng total saponin and ginsenosides Rb1 and Rg1 on
      spinal cord neurons in vitro.
AB  - Spinal cord injury is a major cause of disability and results in many serious
      physical, psychological, and social difficulties. Numerous studies have shown
      that traumatic spinal cord injuries (SCI) lead to neuronal loss and axonal
      degeneration in and around the injury site that cause partial disability or
      complete paralysis. An important strategy in the treatment of SCI is to promote
      neuron survival and axon outgrowth, making possible the recovery of neural
      connections. Using an in vitro survival assay, we have identified ginsenosides
      Rb1 and Rg1, extracted from ginseng root (Panax ginseng C. A. Meyer), as
      efficient neuroprotective agents for spinal cord neurons. These compounds protect
      spinal neurons from excitotoxicity induced by glutamate and kainic acid, as well
      as oxidative stress induced by H(2)O(2). The neuroprotective effects are dose
      dependent. The optimal doses are 20-40 microM for ginsenosides Rb1 and Rg1. The
      effects are specific for Rb1 and Rg1, since a third ginsenoside, Re, did not
      exhibit any activity. Ginseng has been used for thousands of years in the
      treatment of neurological disorders and other diseases in Asia. Ginsenosides Rb1
      and Rg1 represent potentially effective therapeutic agents for spinal cord
      injuries.

PMID- 11822888
TI  - Differential effects of a small, unilateral, 6-hydroxydopamine-induced nigral
      lesion on behavior in high and low responders to novelty.
AB  - The goal of this study was to develop an animal model that evaluates striatal
      specific behavior after partial, unilateral destruction of nigrostriatal neurons.
      6-OHDA (1 microg) was injected intranigrally (day 0) to reduce dopaminergic
      innervation of the dorsal striatum (DS); 6-OHDA (5 microg) was injected to reduce
      innervation of DS and nucleus accumbens (ACC). We analyzed changes in (a)
      behavior regulated by dopamine (DA) release in the DS (hindpaw preference from
      day 5 to day 19, every other day) and the ACC (novelty-induced locomotion on day
      16) and (b) apomorphine-induced rotation (on day 21). We used two types of rat
      that show differences in structure and function of the dopaminergic neurons,
      namely high (HR) and low (LR) responders to novelty. 6-OHDA (1 microg)
      significantly decreased TH immunoreactivity (TH-ir) in the DS and increased
      preference for the hindpaw controlled by the nonlesioned side in HRs and LRs in
      time. Only in LRs was the significant increase of novelty-induced locomotion
      accompanied by a significant increase in TH-ir density in the ACC: this suggests
      a lesion-induced shift in nigrostriatal/mesolimbic balance toward a dominance of
      the mesolimbic system. The higher 6-OHDA dose significantly decreased TH-ir in
      the DS and the ACC and increased preference for the hindpaw controlled by the
      nonlesioned side in HRs and LRs in time. However, this increase occurred
      significantly earlier in LRs than in HRs. Apomorphine elicited contralateral
      rotations solely in LRs, and not in HRs, indicating development of supersensitive
      dopamine receptors in the DS of LRs, but not HRs. The data show that LRs are more
      susceptible to 6-OHDA than HRs. The relevance of the present data for Parkinson's
      disease is discussed.

PMID- 11822887
TI  - Marked dopaminergic cell loss subsequent to developmental, intranigral expression
      of glial cell line-derived neurotrophic factor.
AB  - Glial cell line-derived neurotrophic factor (GDNF) shows potent neuroprotective
      as well as neurorestorative actions on the adult neurons impacted in animal
      models of Parkinson's disease (PD). Long-term pharmaco-physiological effects of
      GDNF on developing dopaminergic (DA) neurons have not yet been explored because
      of technical difficulties in producing prolonged cell type-specific delivery of
      this neurotrophic factor in mammalian embryonic brain. The current studies used
      our previously characterized 9.0-kb tyrosine hydroxylase promoter to produce
      transgenic mice with neuronal cell type-specific expression of GDNF in substantia
      nigra pars compacta (SNc) and locus coeruleus (LC). These mice were used to test
      the parsimonious hypothesis that increased developmental expression of GDNF in
      SNc and LC would significantly enhance the number of postmitotic adult neurons.
      To our surprise, adult transgenic mice carrying the TH9.0kb-GDNF hybrid gene
      showed dramatic reductions in both the numbers and the volumes of SNc-DA and LC
      noradrenergic (NA) neurons by quantitative morphometric analysis. The decrease in
      the number of DA neurons was apparent as early as postnatal day 2, the period
      before the major naturally occurring apoptotic cell death in midbrain. Aged
      transgenic mice exhibited no further significant deficits in motor behaviors.
      These data suggest that continuous, early developmental GDNF expression exerts
      physiological effects on newly differentiated, immature dopamine neurons that
      differ from those observed on more mature and adult DA neurons. Further
      elucidation of the mechanisms underlying differential GDNF actions will greatly
      improve the pharmacological efficacy of GDNF in fetal neural transplantation as
      well as adult neuronal gene therapy in PD patients.

PMID- 11822889
TI  - Electromyographic activity patterns of ankle flexor and extensor muscles during
      spontaneous and L-DOPA-induced locomotion in freely moving neonatal rats.
AB  - In rats, hindlimb postural and locomotor functions mature during the first 3
      postnatal weeks. Previous evidence indicates that maturation of descending
      monoaminergic pathways is important for the postnatal emergence of locomotion
      with adequate antigravity postural support. Here we have studied the effect of
      the monoamine precursor L-DOPA on locomotor activity in freely moving postnatal
      rats (7-9 days old) using electromyographic recordings from ankle extensor
      (soleus) and flexor (tibialis anterior or extensor digitorum longus) muscles.
      Before pharmacological treatment, both muscles were usually silent at rest, and
      during spontaneous movements there was a high degree of coactivation between the
      two antagonists. This was due to a longer electromyographic (EMG) burst duration
      in flexors, which partly overlapped with the extensor burst. L-DOPA
      administration (150 mg/kg) resulted in a marked increase in postural tonic EMG
      activity in extensors which appeared gradually within 10 min after injection and
      was sufficient for the pups to maintain a standing posture with the pelvis raised
      above ground. Thereafter, episodes of locomotion characterized by rhythmic
      reciprocal bursts of EMG activity in flexor and extensor muscles were seen. The L
      DOPA-induced rhythmic EMG pattern was also seen in postnatal rats subjected to a
      midthoracic spinal cord transection, indicating that the effect of L-DOPA on
      motor coordination is exerted primarily at the level of the spinal pattern
      generator. Analysis of EMG burst characteristics showed that the pattern of L
      DOPA-induced locomotion in both intact and spinalized postnatal rats resembled in
      some respects that observed in adults during spontaneous locomotion. The
      appearance of reciprocal activation during L-DOPA-induced locomotion in neonates
      was primarily due to a shortening of the EMG burst duration in flexors, which
      reduced the degree of antagonist coactivation. These results show that the spinal
      cord has the potential to produce coordinated overground locomotion several days
      before such movements are normally expressed in the freely moving animal.

PMID- 11822890
TI  - Relationship between functional deficiencies and the contribution of myelin nerve
      fibers derived from L-4, L-5, and L-6 spinolumbar branches in adult rat sciatic
      nerve.
AB  - The distribution and relative intrafascicular contribution of myelin fibers
      derived from spinal segments L-4 to L-6 were analyzed in adult rat sciatic nerve
      and its main branches, using 200-kDa neurofilament subunit immunodetection in
      previously injured nerve sections in the L-4 or L-5 spinal branch or both. These
      branches' functional contribution was evaluated 16 days after the injury, using
      the method of J. Bain, S. Mackinnon, and D. Hunter (1988, Plast. Reconstr. Surg.
      83: 129-136). A common topographic intrafascicular distribution was found in 69%
      of cases, with notable segregation of L-4 and L-5 fibers and a random
      distribution for L-6 fibers. At sciatic nerve main branch level, L-4 contributes
      almost entirely to the peroneal nerve, L-5 to the tibial nerve, and L-6 and other
      branches to the sural nerve. After injury to L-4, a significant reduction in
      peroneal nerve functional index (PFI) was observed, as was a reduction in print
      length (PL). Injury to L-5 caused a significant reduction in the sciatic (SFI)
      and tibial (TFI) functional nerve indices, an increase in PL, and a reduction in
      the spread between opposite toes (TS). Finally, transection of both L-4 and L-5
      was followed by a significant reduction in all functional indices measured, an
      increase in PL, and a reduction in intermediate toe (ITS) and opposite toe spread
      (TS). The results indicate a direct relationship between the distribution and
      contribution of the spinal nerve fibers forming the sciatic nerve and the
      alteration in functional indices for sciatic, tibial, and peroneal nerves.

PMID- 11822891
TI  - Cytochrome oxidase activity of the suprachiasmatic nucleus and pineal gland in
      rats with portacaval shunt.
AB  - Rhythmic behavioral and biochemical changes have been observed in both human and
      animal models with hepatic insufficiency. The basis of all these alterations is
      the principal endogenous pacemaker, the suprachiasmatic nucleus. The aim of this
      work, therefore, is to determine cytochrome c oxidase activity, a marker of
      neuronal activity and oxidative metabolism, in this nucleus in rats with
      portacaval shunt. In order to do this, this enzyme was histochemically marked and
      quantified by computer-assisted optical densitometry. Results show a reduced
      cytochrome oxidase activity in the suprachiasmatic nucleus in animals with
      portacaval shunts and, inversely, an increase in oxidative metabolism in the
      pineal gland, another circadian structure. However, the activity measured in a
      noncircadian brain structure, the hippocampus, which served as a control, showed
      no changes with surgery. Additionally, locomotor activity was assessed by
      actimeters and revealed a clearly reduced activity in animals with portacaval
      shunt. We conclude that the suprachiasmatic nucleus is possibly involved in the
      rhythmic changes associated with hepatic insufficiency.

PMID- 11822892
TI  - Postischemic angiogenic factor expression in stroke-prone rats.
AB  - Spontaneously hypertensive stroke-prone rats (SHRSP), a model for genetic stroke
      susceptibility, suffer spontaneous stroke and enhanced injury after experimental
      stroke, in part due to abnormal cerebrovascular development. We hypothesized that
      angiopoietin system genes in SHRSP may follow unique patterns of expression after
      experimentally induced stroke. SHRSP, hypertensive control rats (SHR), and
      normotensive controls (WKY) were subjected to experimental middle cerebral artery
      occlusion, and brain RNA was analyzed for expression of angiogenic genes.
      Expression of angiopoietin-2 increased after stroke in all rat strains and was
      significantly enhanced in SHRSP compared with control strains. In addition,
      expression of angiopoietin-1 and the angiopoietin receptor dropped markedly after
      stroke in SHRSP animals, but was not different after ischemia in SHR and WKY
      strains. Thus, the SHRSP brain elaborates a unique and specific pattern of
      angiopoietin system gene expression after stroke which may underlie stroke
      susceptibility of these rats.

PMID- 11822893
TI  - Mitochondrial membrane potential selects hybridomas yielding high viability in
      fed-batch cultures.
AB  - Prior research (Follstad, B. D.; Wang, D. I. C.; Stephanopoulos, G. Mitochondrial
      membrane potential differentiates cells resistant to apoptosis in hybridoma
      cultures. Eur. J. Biochem. 2000, 267, 6534-6540.) identified mitochondrial
      membrane potential (MMP) as a marker of hybridoma subpopulations resistant to
      apoptosis caused by a variety of apoptosis inducers. In this study, we
      investigated the viability of hybridoma cell cultures inoculated with cells of
      varying MMP in regular fed-batch operation. A hybridoma cell population was
      separated using FACS into subpopulations based on their mean mitochondrial
      membrane potential (MMP) as measured using the common mitochondrial stain,
      Rhodamine 123 (Rh123). These subpopulations showed dramatic differences in their
      apoptotic death kinetics. Fed-batches inoculated with a high MMP subpopulation
      reached higher viable cell concentrations and viabilities that were maintained
      for prolonged periods of time relative to fed-batches inoculated with low MMP
      subpopulations. These results underline the heterogeneous nature of hybridoma
      cell cultures and suggest that mitochondrial physiology is a critical parameter
      determining culture performance.

PMID- 11822894
TI  - Global gene expression differences associated with changes in glycolytic flux and
      growth rate in Escherichia coli during the fermentation of glucose and xylose.
AB  - The simplicity of the fermentation process (anaerobic with pH, temperature, and
      agitation control) in ethanologenic Escherichia coli KO11 and LY01 makes this an
      attractive system to investigate the utility of gene arrays for biotechnology
      applications. By using this system, gene expression, glycolytic flux, and growth
      rate have been compared in glucose-grown and xylose-grown cells. Although the
      initial metabolic steps differ, ethanol yields from both sugars were essentially
      identical on a weight basis, and little carbon was diverted to biosynthesis.
      Expression of only 27 genes changed by more than 2-fold in both strains. These
      included induction of xylose-specific operons (xylE, xylFGHR, and xylAB)
      regulated by XylR and the cyclic AMP-CRP system and repression of Mlc-regulated
      genes encoding glucose uptake (ptsHIcrr, ptsG) and mannose uptake (manXYZ) during
      growth on xylose. However, expression of genes encoding central carbon metabolism
      and biosynthesis differed by less than 2-fold. Simple statistical methods were
      used to investigate these more subtle changes. The reproducibility (coefficient
      of variation of 12%) of expression measurements (mRNA as cDNA) was found to be
      similar to that typically observed for in vitro measurements of enzyme
      activities. Using Student's t test, many smaller but significant sugar-dependent
      changes were identified (p < 0.05 in both strains). A total of 276 genes were
      more highly expressed during growth on xylose; 307 genes were more highly
      expressed with glucose. Slower growth (lower ATP yield) on xylose was accompanied
      by decreased expression of 62 genes concerned with the biosynthesis of small
      molecules (amino acids, nucleotides, cofactors, and lipids), transcription, and
      translation; 5 such genes were expressed at a higher level. In xylose-grown
      cells, 90 genes associated with the transport, catabolism, and regulation of
      pathways for alternative carbon sources were expressed at higher levels than in
      glucose-grown cells, consistent with a relaxation of control by the cyclic AMP
      CRP regulatory system. Changes in expression of genes encoding the Embden
      Meyerhof-Parnas (EMP) pathway were in excellent agreement with calculated changes
      in flux for individual metabolites. Flux through all but one step, pyruvate
      kinase, was predicted to be higher during glucose fermentation. Expression levels
      (glucose/xylose) were higher in glucose-grown cells for all EMP genes except the
      isoenzymes encoding pyruvate kinase (pykA and pykF). Expression of both
      isoenzymes was generally higher during xylose fermentation but statistically
      higher in both strains only for pykF encoding the isoenzyme activated by fructose
      6-phosphate, a key metabolite connecting pentose metabolism to the EMP pathway.
      The coordinated changes in expression of genes encoding the EMP pathway suggest
      the presence of a common regulatory system and that flux control within the EMP
      pathway may be broadly distributed. In contrast, expression levels for genes
      encoding the Pentose-Phosphate pathway did not differ significantly between
      glucose-grown and xylose-grown cells.

PMID- 11822896
TI  - Separation characteristics of liquid nematode cultures and the design of recovery
      operations.
AB  - Production of nematode-based pesticides involves the recovery of a viable
      nematode life stage known as the infective juvenile (IJ) from fermentation broth.
      Waste components to be separated from the IJs include non-IJ life stages, dead
      nematodes, nematode debris, spent media, and the nematode's associated bacteria.
      This paper reports separation characteristics of liquid cultures and suspensions
      of the nematodes Phasmarhabditis hermaphrodita, Steinernema feltiae, and
      Heterorhabditis megidis measured at small scale. Separation characteristics were
      determined for dead-end filtration, gravity settling and flotation. Results were
      used to identify large-scale recovery procedures. Separation of culture liquid by
      dead-end filtration of the crude fermentation broth was not possible due to rapid
      blinding of filters. However, nematode-water suspensions prepared by gravity
      settling could be concentrated using this separation method. Settling tests
      indicated that IJs could be efficiently separated from culture liquid by
      centrifugation but not by gravity settling. Examination of the effects of
      nematode concentration indicated an optimum concentration for gravity settling
      that may entail modest dilution of the fermentation broth. Flocculation of
      insoluble spent media in suspensions of P. hermaphrodita prevented its separation
      from nematodes by gravity settling. However, attachment of air bubbles to spent
      media allowed removal by flotation. Finally, adjustment of continuous phase
      density using sucrose allowed separation of non-IJ life stages, dead nematodes,
      and discarded cuticles from the IJs by flotation. The efficiency of this
      separation decreased with increasing nematode-solute contact time.

PMID- 11822897
TI  - Degradation of water-insoluble dyes by microperoxidase-11, an effective and
      stable peroxidative catalyst in hydrophilic organic media.
AB  - Microperoxidase-11 (MP-11), a heme-containing undecapeptide, derived from horse
      heart cytochrome c was utilized as a peroxidative catalyst. Catalytic
      characteristics of MP-11 in hydrophilic organic media were studied using 2,6
      dimethoxyphenol as a reducing substrate in a series of organic solvents at
      various concentrations, indicating that MP-11 was active in water-miscible
      organic solvents but at least 5% water was compulsory for the catalytic action.
      Thus, MP-11 was not active in hydrophobic solvents. The pH of the water portion
      in the media affected the reaction rate. The optimal pH was found to be 9, where
      a release of protons from either an oxidizing or reducing substrate to the media
      was facilitated. The decolorization of water-insoluble synthetic dyes by MP-11 in
      90% methanol was attempted. MP-11 showed effective decolorization activities
      against either azo or anthraquinone dyes. The degradation pathway for Solvent
      Orange 7 was investigated in detail, showing that MP-11 catalyzed the oxidative
      cleavage of the azo linkage to generate 1,2-naphthoquinone and 2,4-dimethylphenol
      as key intermediates.

PMID- 11822895
TI  - Continuous cultivation of the diatom Nitzschia laevis for eicosapentaenoic acid
      production: physiological study and process optimization.
AB  - The continuous cultures of the diatom Nitzschia laevis were performed at
      different dilution rates (D) and feed glucose concentrations (S(0)) to
      investigate cellular physiological responses and its production potential of
      eicosapentaenoic acid (EPA). Steady-state cell dry weight, residual glucose
      concentration, cell growth yield, specific glucose consumption rate, and fatty
      acid profiles were investigated within the range of D from 0.1 to 1.0 day(-1)
      (S(0) fixed at 20 g/L) and the range of S(0) from 5 to 35 g/L (D fixed at 0.3
      day(-1)), respectively. The highest EPA productivity of 73 mg L(-1) day(-1) was
      obtained at D = 0.5 day(-1) and S(0) = 20 g/L. However, when the continuous
      culture achieved high productivities of EPA at certain dilution rates and feed
      glucose concentrations, glucose in the feed could not be consumed completely.
      Accordingly, the continuous culture was evaluated in terms of both EPA
      productivity (P) and glucose assimilation efficiency (E). The parameter eta,
      defined as the product of P and E, was used as an overall performance index.
      Since eta is a function of the two independent variables D and S(0), we employed
      a central composite design to optimize D and S(0) for the highest eta value.
      Based on the experimental results of the design, a second-order polynomial
      equation was established to represent the relationship between eta and D and
      S(0). The optimal values of D and S(0) were subsequently determined as 0.481 day(
      1) and 15.56 g/L, respectively by the empirical model. The verification
      experiment confirmed the validity of the model. Under the optimal conditions, eta
      value reached 46.5 mg L(-1) day(-1), suggesting a considerably high efficiency of
      the continuous culture of N. laevis in terms of EPA production and glucose
      utilization.

PMID- 11822898
TI  - Mechanical stability of immobilized biocatalysts (CLECs) in dilute agitated
      suspensions.
AB  - Cross-linked enzyme crystals (CLECs) are a novel form of immobilized biocatalyst
      designed for application in industrial biotransformation processes. In this work
      we have investigated the mechanical stability of agitated CLEC suspensions in
      relation to the design and scale-up of bioconversions carried out in stirred-tank
      reactors. By careful control of the crystallization conditions yeast alcohol
      dehydrogenase I (YADHI) microcrystals of different size were first prepared
      having either an hexagonal (approximately 12 microm) or rod-shaped (approximately
      4.6 microm) morphology. These were then cross-linked with glutaraldehyde to form
      CLECs. The rate of breakage of the CLEC suspensions was subsequently measured in
      a rotating disk shear device (total volume, 11 mL) by monitoring the change in
      crystal size distribution with time. This device is designed to mimic the shear
      and energy dissipation rates found in a range of process scale equipment and may
      be used to study the mechanical stability of any immobilized biocatalyst
      preparation. Experiments were performed as a function of the speed and duration
      of disk rotation, CLEC concentration (0.26-2.5 mg.mL(-1)) and energy dissipation
      rate (2.2 x 10(3) to 6.8 x 10(5) W.kg(-1)). No breakage of the rod-shaped CLECs
      was observed over the entire range of experimental conditions investigated.
      Breakage of the larger hexagonal-shaped CLECs did occur, however, at energy
      dissipation rates, epsilon(max), above 1.0 x 10(5) W.kg(-1), where the calculated
      length scale of turbulence was around 2.0 microm. Based on visual observation of
      the sheared CLEC suspensions and models of crystal breakage, it was concluded
      that breakage of the hexagonal-shaped CLECs occurred due to shear induced
      attrition. Measurement of the catalytic activity of both the hexagonal and rod
      shaped CLECs showed no significant change in activity before and after shearing.

PMID- 11822899
TI  - Two-stage culture process for improved production of ganoderic acid by liquid
      fermentation of higher fungus Ganoderma lucidum.
AB  - Investigations on the impact of pellet size on the cellular oxygen uptake and
      accumulation of ganoderic acid (GA) suggested the favorable effect of oxygen
      limitation on GA formation by the higher fungus Ganoderma lucidum. A two-stage
      fermentation process was thus proposed for enhanced GA production by combining
      conventional shake-flask fermentation with static culture. A high cell density of
      20.9 g of DW/L (DW = dry cell weight) was achieved through a 4-day shake-flask
      fermentation followed by a 12-day static culture. A change in the cell morphology
      and a decrease in the sugar consumption rate were observed during the static
      culture. The GA production in the new two-stage process was considerably enhanced
      with its content increased from 1.36 (control) to 3.19 mg/100 mg of DW, which was
      much higher than previously observed.

PMID- 11822900
TI  - Internal and external mass transfer in biofilms grown at various flow velocities.
AB  - It appears that biofilms arrange their internal structure according to the flow
      velocity at which they are grown, which affects the internal mass transfer rate
      and microbial activity. In biofilms grown at various flow velocities we
      determined the vertical profiles of the local relative effective diffusivity
      (termed D(l)) at several locations within each biofilm. From these profiles we
      calculated the surface-averaged relative effective diffusivity (termed D(sa)) at
      various distances from the bottom and plotted it against these distances. The
      D(sa) decreased linearly toward the bottom, forming well-defined profiles that
      were different for each biofilm. The gradients of these profiles were multiplied
      by the diffusivity of oxygen, zeta = D(w) dD(sa)/dz, and plotted versus the flow
      velocity at which each biofilm was grown. The gradients were low at flow
      velocities below 10 cm/s, reached a maximum at a flow velocity of 10 cm/s, and
      decreased again at flow velocities exceeding 10 cm/s. The existence of a maximum
      indicates a possibility that two opposing forces were affecting the slope of the
      profiles. To explain these observations we hypothesized that biofilms, depending
      on the flow velocity at which they are grown, arrange their internal architecture
      to control (1) the nutrient transport rate and (2) the mechanical pliability
      needed to resist the shear stress of the water flowing past them. It appears that
      biofilms attempt to satisfy the second goal first, to increase their mechanical
      strength, and that they do so at the expense of the nutrient transfer rate to
      deeper layers. This strength increase is associated with an increase in biofilm
      density, which slows down the internal mass transport rate. Biofilms grown at low
      flow velocities exhibit low density and high effective diffusivity but cannot
      resist higher shear stress, whereas biofilms grown at higher flow velocities are
      denser and can resist higher shear stress but have a lower effective diffusivity.

PMID- 11822901
TI  - Dynamics of oxygen evolution and biomass production during cultivation of
      Agardhiella subulata microplantlets in a bubble-column photobioreactor under
      medium perfusion.
AB  - Cell and tissue cultures derived from macrophytic marine red algae are potential
      platforms for unique secondary metabolites. This work presents the first
      successful bioreactor cultivation study of an in vitro tissue culture derived
      from a macrophytic marine red alga. Specifically, the photosynthetic growth
      characteristics of a novel microplantlet suspension culture established from the
      macrophytic marine red alga Agardhiella subulata were studied. A bubble-column
      bioreactor with external illumination (43 microE m(-2) s(-1), 10:14 LD
      photoperiod), liquid medium perfusion, and 3800 ppm CO(2) in the aeration gas
      provided sufficient light and nutrient delivery for sustained growth of the
      microplantlet suspension at 24 degrees C and pH 8. Microplantlets, which
      consisted of shoot tissues of 3-5 mm length branching out from a common center,
      were not friable in a bubble-aerated suspension of about 1100 plantlets per
      liter. Since the microplantlet tissues were not friable, only batch and fed-batch
      cultivation modes were considered. Batch cultivation was phosphate-limited in
      ASP12 artificial seawater medium. However, cultivation at a medium perfusion rate
      of 20% per day avoided phosphate limitation and extended the growth phase to
      provide plantlet mass densities exceeding 14 g FW L(-1) (3.7 g DW L(-1)) after 50
      days of cultivation if the suspension was not sampled. The specific oxygen
      evolution rate vs cultivation time profile possessed a significant pulse within
      the 14 days following inoculation and then leveled off at longer times. In
      recognition of this nonexponential growth pattern, a new photobioreactor growth
      model was developed that used the oxygen evolution rate vs time profile to
      predict the biomass growth curve in perfusion culture. Model predictions agreed
      reasonably with the measured growth curves.

PMID- 11822902
TI  - Enhanced mixing and mass transfer in a recirculation loop results in high cell
      densities in a roller bottle reactor.
AB  - A recirculation loop added to a large-scale roller bottle reactor resulted in
      high cell densities as compared to standard roller bottles. Four different
      mammalian cell lines reached an average maximum density equal to 5.4 x 10(6)
      cells /mL (sigma = 0.263), which was between 2.13 and 2.95 times greater than the
      densities in roller bottles without recirculation using the same cell lines. The
      high densities were maintained over long durations (>25 days) while the reactor
      operated with continuous perfusion. The increased densities are attributed to
      enhanced liquid mixing and oxygen transfer that occur as a result of the
      recirculation loop. Models were developed that describe axial liquid flow and
      oxygen transfer in both the sample loop and the reactor growth chamber. Axial
      dispersion and oxygen transfer coefficients are presented for a variety of
      operating conditions. The increased oxygen transfer characteristics of the
      reactor allow for easy scale-up of roller bottle cultures by operating at larger
      volumes with greater liquid depths than conventional roller bottles permit. The
      surface-area-to-volume ratio in the tests performed was 0.206 versus 1.16 cm(-1)
      in a standard roller bottle.

PMID- 11822904
TI  - Separation of large circular DNA by electrophoresis in agarose gels.
AB  - The electrophoresis of circular DNA, ranging in size from 4.4 kilobase pairs
      (kbp) to 220 kbp, was studied in agarose gels. Bacterial artificial chromosome
      (BAC) DNA was used as a source of large supercoiled and open circular (relaxed)
      forms. The open circles above approximately 50 kbp were trapped at the sample
      wells of 1% agarose gels during electrophoresis at 3 V/cm. Field inversion gel
      electrophoresis (FIGE) was used to relieve the trapping of the open circles in
      the gels. Using FIGE (30 s forward pulse time), open circles with sizes of 115
      and 220 kbp required reverse pulse times of 3 and 6 s, respectively, to free the
      circles from open-ended gel fibers. A minimum in the gel velocity of the open
      circles was measured at approximately 20 kbp. Open circles below approximately 20
      kbp migrated slower than the supercoiled forms, and above 20 kbp the order was
      reversed. These results indicate that when the size of the open circles exceeded
      the average pore size of a gel and it was forced to span multiple pores, the open
      circles gained a mobility advantage. Decreasing the ionic strength of the
      electrophoresis buffer significantly decreased the mobility of the smaller
      circles and slightly increased the mobility of the larger circles.

PMID- 11822903
TI  - Immobilized metal affinity chromatography without chelating ligands: purification
      of soybean trypsin inhibitor on zinc alginate beads.
AB  - Immobilized metal affinity chromatography (IMAC) is a widely used technique for
      bioseparation of proteins in general and recombinant proteins with polyhistidine
      fusion tags in particular. An expensive and critical step in this process is
      coupling of a chelating ligand to the chromatographic matrix. This chelating
      ligand coordinates metal ions such as Cu(2+), Zn(2+), and Ni(2+), which in turn
      bind proteins. The toxicity of chemicals required for coupling and their slow
      release during the separation process are of considerable concern. This is an
      important issue in the context of purification of proteins/enzymes which are used
      in food processing or pharmaceutical purposes. In this work, a simpler IMAC
      design is described which should lead to a paradigm shift in the application of
      IMAC in separation. It is shown that zinc alginate beads (formed by chelating
      alginate with Zn(2+) directly) can be used for IMAC. As "proof of concept",
      soybean trypsin inhibitor was purified 18-fold from its crude extract with 90%
      recovery of biological activity. The dynamic binding capacity of the packed bed
      was 3919 U mL(-1), as determined by frontal analysis. The media could be
      regenerated with 8 M urea and reused five times without any appreciable loss in
      its binding capacity.

PMID- 11822905
TI  - Comparison of the emulsion characteristics of Rhodococcus erythropolis and
      Escherichia coli SOXC-5 cells expressing biodesulfurization genes.
AB  - Biodesulfurization of fuel oils is a two-phase (oil/water) process which may
      offer an interesting alternative to conventional hydrodesulfurization due to the
      mild operating conditions and reaction specificity afforded by the biocatalyst.
      For biodesulfurization to realize commercial success, a variety of process
      considerations must be addressed including reaction rate, emulsion formation and
      breakage, biocatalyst recovery, and both gas and liquid mass transport. This
      study evaluates emulsion formation and breakage using two biocatalysts with
      differing hydrophobic characteristics. A Gram-positive (Rhodococcus erythropolis)
      biocatalyst, expressing the complete 4S desulfurization pathway, and a Gram
      negative biocatalyst (Escherichia coli), expressing only the gene for conversion
      of dibenzothiophene (DBT) to DBT sulfone, are compared relative to their ability
      to convert DBT and the ease of phase separation as well as biocatalyst recovery
      following desulfurization.

PMID- 11822906
TI  - Separation of MBP fusion proteins through affinity membranes.
AB  - Cellulose microporous membranes have been modified in order to obtain a
      stationary phase specific for the recovery of a class of fusion proteins
      containing the maltose binding protein domain, through affinity chromatography
      separations. The feasibility of a single step separation process for the recovery
      of large amounts of the desired product has been considered. To that purpose, a
      preparative scale module has been realized, suitable for flat sheet membranes.
      The affinity matrix used proved to be highly selective toward the fusion proteins
      examined. The binding capacity determined is comparable with the nominal binding
      capacity of commercially available supports. The influence of the relevant
      working parameters, such as flow rate, on the performances of the recovery
      process has been studied.

PMID- 11822908
TI  - Reaction equilibrium of penicillin G with amberlite LA-2 in a nonpolar organic
      solvent.
AB  - Studies have been made of the reactive extraction of penicillin G by Amberlite LA
      2, a secondary amine, dissolved in kerosene. On the basis of the previous works
      about extraction equilibria of monocarboxylic acids by some secondary amines in
      low polar organic solvents, four equilibrium models were suggested to describe
      the reaction equilibrium of penicillin G in the liquid-liquid extraction system.
      The calculated results from the models were compared with the experimental data
      of 96 runs, and only two equilibrium models seemed to be probable. Ultimately,
      the most reasonable extraction equilibrium model was chosen through spectroscopic
      studies on organic solutions obtained by five specific extraction equilibrium
      experiments.

PMID- 11822907
TI  - Complete deoxygenation from a hemoglobin solution by an electrochemical method
      and heat treatment for virus inactivation.
AB  - Hemoglobin (Hb) has been widely studied as a raw material for various types of
      oxygen carriers. In the purification of Hb from red blood cells including virus
      inactivation and denaturation of other proteins and the long-term storage of Hb
      vesicles (HbV), a deoxygenation process is one of the important processes because
      of the high stability of deoxygenated Hb to heating and metHb formation. Though
      an oxygenated Hb solution can be deoxygenated with an artificial lung, it is
      difficult to reduce the oxygen partial pressure of the Hb solution to less than
      10 Torr. We developed an electrochemical system for complete deoxygenation of the
      Hb solution at the cathode compartment using hydrogen containing nitrogen gas at
      the anode compartment. Oxygen in the Hb solution was reduced to OH(-) at the
      cathode compartment within several minutes at a potential value of -1.67 V and
      was finally converted to water by neutralization with H(+) from the anode in the
      whole system. The resulting completely deoxygenated Hb could tolerate heat
      treatment at 62 degrees C for 10 h with no denaturation of deoxygenated Hb. The
      metHb formation rate of reoxygenated Hb at 37 degrees C was not changed after
      heat treatment. Furthermore, vesicular stomatitis virus (VSV) could be
      inactivated at an inactivation degree of more than 5.96 log by heat treatment.

PMID- 11822910
TI  - Stationary and microcarrier cell culture processes for propagating Japanese
      encephalitis virus.
AB  - Inactivated mouse-brain-derived vaccines for Japanese encephalitis virus (JEV)
      have been used for many years. Recently, attempts have been made to employ
      cultured Vero cells to replace mouse brain tissues for developing cell-culture
      derived vaccines that will be more suitable for worldwide usage. In this study,
      JEV replication processes in Vero and BHK cells and between stationary and
      microcarrier culture systems were investigated. Our results demonstrated that a
      stationary Vero cell culture system produced higher viral titers of JEV,
      including the Beijin-1 vaccine strain and the attenuated strain CH2195LA, than
      microcarrier culture did. BHK cells showed less significant differences in their
      replication kinetics between stationary and microcarrier cultures. Reducing serum
      concentration during infection led to an overall decrease of JEV production in
      Vero cells but an increase in BHK cells. By establishing a complete serum-free
      Vero cell culture, the microcarrier system resulted in a more than 4-log lowered
      yield compared to that of the stationary culture for JEV production. Thus, the
      stationary culture is the most efficient system for JEV production from cultured
      Vero cells.

PMID- 11822909
TI  - Recovery of recombinant cutinase using detergent foam.
AB  - Foam generated by vigorous stirring of a nonionic detergent, Triton X-114, was
      used for the recovery of recombinant cutinase expressed by Saccharomyces
      cerevisiae. The enzyme with a hydrophobic fusion tag, (Trp-Pro)(4), was recovered
      with a higher yield as compared to the wild-type cutinase, indicating the
      involvement of hydrophobic interactions in protein isolation with the foam. The
      influence of various factors including volume, dilution, pH, different additives,
      and cell concentration in the medium on enzyme recovery was investigated.
      Interaction of the enzyme with detergent was monitored using fluorescence
      spectroscopy. No significant changes in protein conformation after the isolation
      procedure were observed using circular dichroism.

PMID- 11822911
TI  - Effects of ammonia and glucosamine on the heterogeneity of erythropoietin
      glycoforms.
AB  - Recombinant human erythropoietin (EPO) is a glycoprotein produced as a
      therapeutic agent from mammalian cell cultures for the treatment of anemia
      associated with severe kidney damage. The EPO structure has a high glycan content
      which is essential for bioactivity but shows considerable molecular
      heterogeneity. The cell culture conditions that affect the heterogeneity of the
      glycoforms of EPO are not well understood. However, the accumulation of ammonia
      in culture is one factor that has been associated with an enhanced heterogeneity
      of glycoforms. In this report we investigate the metabolic perturbations
      associated with ammonia and glucosamine that may give rise to an altered pattern
      of EPO glycosylation. Recombinant human erythropoietin was synthesized in serum
      free cultures of transfected Chinese hamster ovary (CHO) cells. The molecular
      heterogeneity of erythropoietin was increased by supplementation of cultures with
      either ammonia or glucosamine. The enhanced molecular heterogeneity was shown to
      be due to variable glycosylation that resulted in EPO with an enhanced molecular
      weight and isoelectric point range. Enzymatic removal of the glycan moiety of EPO
      in all cases resulted in a single molecular form with a molecular weight of 18
      000, which corresponded to non-glycosylated EPO. The variable glycosylation was
      consistent with reduced sialylation and antennarity of the carbohydrate
      structures present on the three N-linked sites of EPO. In the presence of ammonia
      (>30 mM) the proportion of tetrasialylated and tetraantennary glycan structures
      were reduced by 73% and 57%, respectively, as determined by HPLC analysis. Such
      changes were also observed, although to a lesser extent (41% and 37%), by an
      increase in the glucosamine concentration (>10 mM) in the medium. The enhanced
      heterogeneity of the glycan structures coincided with a significant increase in
      the intracellular UDP-N-acetylhexosamine (UDP-GNAc) pool. The measured UDP-GNAc
      level was up to 2 orders of magnitude higher in the presence of either
      glucosamine or ammonia. However, the changes in the glycosylation profiles
      induced by either glucosamine or ammonia were significantly different even at the
      same intracellular UDP-GNAc concentration. This suggests that the enhanced EPO
      heterogeneity could not be mediated solely by the increased UDP-GNAc level.
      Glucosamine (but not ammonia) was shown to cause significant inhibition of
      glucose transport into the cells, which could induce a different pattern of
      primary metabolism.

PMID- 11822912
TI  - Solubility and diffusion of nitrogen in maltodextrin/protein tablets.
AB  - The gas transport properties of compacted tablets consisting of an amorphous
      mixture of maltodextrin and sodium caseinate were studied by dissolving nitrogen
      gas in the tablets and then determining the gas release over time as a function
      of temperature and water activity. Gas was dissolved in the tablet matrix by
      heating the tablets under pressure, generally to temperatures above the glass
      transition temperature of the matrix, holding them at these conditions for a
      specified time and then rapidly cooling them while maintaining the external
      pressure. The solubility of nitrogen was found to be largely determined by the
      free volume of the matrix, which in turn can be influenced to some degree by
      thermal and pressure treatments during gas loading. At the levels of free volume
      studied, the dissolved nitrogen is densely packed in the free volume, the packing
      density being virtually independent of the externally applied pressure. Release
      of gas from the tablets at temperatures below the glass transition temperature is
      generally well described by Fickian diffusion. The effective diffusion
      coefficient of gas release is strongly dependent on the microstructure and
      porosity of the tablet matrix, and an approximate model describing the
      relationship between tablet structure and rate of gas release is formulated. The
      model is in semiquantitative agreement with the rates of gas diffusion obtained
      for tablets and dense granules. Owing to the structural heterogeneity and
      variability of the tablets and the history-dependent properties of the tablet
      matrix, the effective diffusion coefficients of gas release from the tablets
      showed a relatively large spread. The temperature dependence of diffusional
      release follows an Arrhenius relation below the glass transition temperature.
      This allows the prediction of the nitrogen retention in the tablets as function
      of time, temperature and pressure.

PMID- 11822913
TI  - Specific effects of synthetic oligopeptides on cultured animal cells.
AB  - Synthetic oligopeptides, tri- to pentaglycine and tri- and tetraalanine, were
      found to enhance viable cell density and culture viability when applied at
      concentrations higher than milllimolar to the cultures of a model hybridoma line.
      Oligoalanines, in addition, enhanced monoclonal antibody yields. Oligoglycines
      promoted solely the cell growth, unless the batch culture was fed with a medium
      concentrate. Examination of the effects of various tripeptides composed of
      glycine, alanine, serine, threonine, lysine, and histidine showed that some of
      the peptides promoted the growth of the culture, while other peptides suppressed
      the growth and enhanced the monoclonal antibody yield. Determination of the
      levels of amino acids and peptides in culture media indicated that the observed
      changes of culture parameters were caused by intact peptide molecules, rather
      than by amino acids liberated from the peptides by enzymic cleavage.

PMID- 11822914
TI  - Influence of fungal elicitors on production of ajmalicine by cell cultures of
      Catharanthus roseus.
AB  - Suspension cultures of Catharanthus roseus (C. roseus) were elicited with fungal
      cell wall fragments of Aspergillus niger (A. niger), Fusarium moniliforme (F.
      moniliforme), and Trichoderma viride (T. viride). The effects of elicitor dosage,
      exposures time, and age of subculture on ajmalicine accumulation were studied. A
      higher concentration of elicitor extract responded positively to C. roseus
      suspension cultures. Ajmalicine accumulation increased by about 3-fold when cells
      were treated with A. niger, F.moniliforme, and T. viride. The maximum ajmalicine
      production (75 microg g(-1) dry weight (DW)) was observed in cells treated with
      T. viride. Cell cultures were elicited with 5% preparation of A. niger, F.
      moniliforme, and T. viride and exposed for 24, 48, 72, and 96 h. for elicitation.
      Suspension cultures elicited with T. viride for 48 h showed a 3-fold increase (87
      microg g(-1) DW) in ajmalicine contents, whereas A. niger and F. moniliforme
      synthesized a 2-fold increase in alkaloid and yielded 52 and 56 microg g(-1) DW
      ajmalicine, respectively. C. roseus cells of different age (5,10, 15, 20, and 25
      days old) were treated with a 5% elicitor of A. niger, F. moniliforme, and T.
      viride and investigated elicitors activity at different age of cell cultures.
      Maximum yield 166 microg g(-1) DW of ajmalicine was synthesized in 20 day old
      suspension cultures treated with T. viride. A longer period of incubation of cell
      cultures with elicitors adversely affected the ajmalicine synthesis.

PMID- 11822915
TI  - Hyaluronate sodium injections for osteoarthritis: hope, hype, and hard truths.

PMID- 11822916
TI  - Evidence in upheaval: incorporating observational data into clinical practice.

PMID- 11822917
TI  - Antibiotics for common respiratory tract infections in adults.
AB  - A thorough review of the published information indicates that antibiotics rarely
      benefit acute bronchitis, exacerbations of asthma and chronic bronchitis, acute
      pharyngitis, and acute sinusitis, although they are commonly prescribed for these
      illnesses. Rather than prescribing them for these conditions, practitioners
      should explain to their patients that antibiotics, which have numerous adverse
      effects, will not hasten resolution of their symptoms, which will often respond
      to other medications. Most patients will accept this approach if the clinician
      addresses their concerns, shows a personal interest in them, discusses the
      expected course of the ailment, and explains the treatment.

PMID- 11822918
TI  - Association of nonsteroidal anti-inflammatory drugs with first occurrence of
      heart failure and with relapsing heart failure: the Rotterdam Study.
AB  - BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been associated
      with first hospitalization for congestive heart failure (CHF). It is likely,
      however, that NSAIDs precipitate a relapse but are less likely to induce a first
      occurrence of (incident) heart failure. METHODS: A total of 7277 participants in
      the Rotterdam Study were followed up from the interview date until the first of
      the following events: a diagnosis of incident heart failure, death, removal, or
      end of the follow-up period. Excluded from the study population were all
      participants with prevalent heart failure at baseline. Exposure to NSAIDs and
      other medication was calculated on the basis of automated data on filled drug
      prescriptions in the pharmacies within the study area. In a second analysis, we
      followed up all participants with incident heart failure until the first relapse
      or the end of follow-up. RESULTS: Incident heart failure was encountered in 345
      participants during follow-up. Current use of NSAIDs was associated with a
      relative risk of incident heart failure of 1.1 (95% confidence interval [CI], 0.7
      1.7), after adjustment for age, sex, and concomitant medication. In patients with
      prevalent heart failure who filled at least 1 NSAID prescription since diagnosis
      of heart failure, the univariate and adjusted relative risks of a relapse were
      3.8 (95% CI, 1.1-12.7) and 9.9 (95% CI, 1.7-57.0), respectively. CONCLUSIONS: The
      use of NSAIDs is not associated with an increased risk of incident heart failure.
      In patients with prevalent heart failure, current use of NSAIDs is associated
      with a substantially increased risk of a relapse.

PMID- 11822919
TI  - Smoking and risk of coronary heart disease among women with type 2 diabetes
      mellitus.
AB  - BACKGROUND: Although the association between smoking and increased risk of
      coronary heart disease (CHD) is well established in the general population, this
      relationship is less well-defined among individuals with diabetes. OBJECTIVE: To
      assess the relationship between cigarette smoking and risk of CHD among women
      with type 2 diabetes mellitus in the Nurses' Health Study cohort. METHODS: The
      Nurses' Health Study, a prospective cohort study of 121,700 US female registered
      nurses surveyed in 11 states and followed up from July 1, 1976, through July 1,
      1996, involved a total of 6547 women diagnosed as having type 2 diabetes
      mellitus. Incident cases of CHD were our main outcome measure in this study.
      RESULTS: We documented 458 incident cases of CHD (200 fatal CHD-related cases and
      258 nonfatal myocardial infarctions) during 20 years (68,227 person-years) of
      follow-up. We found a dose-response relationship between current smoking status
      and risk of CHD among diabetic women. Compared with never smokers, the relative
      risks (RRs) for CHD were 1.21 (95% confidence interval [CI], 0.97-1.51) for past
      smokers, 1.66 (95% CI, 1.10-2.52) for current smokers of 1 to 14 cigarettes per
      day, and 2.68 (95% CI, 2.07-3.48) for current smokers of 15 or more cigarettes
      per day in multivariate analyses (P<.001 for trend). The multivariate RR of CHD
      among diabetic women who had stopped smoking for more than 10 years was similar
      to that among diabetic women who were never smokers (RR, 1.01; 95% CI, 0.73
      1.38). In secondary analyses involving diabetic and nondiabetic women, the
      multivariate-adjusted RR of CHD for those with diabetes who currently smoked (>
      or = 15 cigarettes per day) compared with those who never smoked was 7.67 (95%
      CI, 5.88-10.01). CONCLUSIONS: Cigarette smoking is strongly associated with an
      increased risk of CHD among women with type 2 diabetes mellitus. Furthermore,
      quitting smoking seems to decrease this excess risk substantially; women with
      diabetes should be strongly advised against smoking.CK

PMID- 11822920
TI  - Insurance coverage, medical conditions, and visits to alternative medicine
      providers: results of a national survey.
AB  - BACKGROUND: In 1997, patients made an estimated 629 million visits to
      complementary and alternative medicine (CAM) providers; however, little is known
      about factors associated with visits to CAM providers. OBJECTIVE: To examine the
      effect of insurance coverage on frequency of use of CAM providers. METHODS: We
      conducted a nationally representative, random household telephone survey of 2055
      adults. MAIN OUTCOME MEASURE: The number of visits made to CAM providers.
      RESULTS: An estimated 44% of the US population used at least 1 CAM therapy in
      1997. Of those using CAM, 52% had seen at least 1 CAM provider in the last year.
      Among those who used a CAM therapy, factors independently associated with seeing
      a provider were having been in the upper quartile of visits to conventional
      providers in the last year (adjusted odds ratio [AOR], 2.00; 95% confidence
      interval [CI], 1.33-3.01), female sex (AOR, 1.67; 95% CI, 1.17-2.38), and having
      used the therapy to treat diabetes (AOR, 5.20; 95% CI, 1.40-19.40), cancer (AOR,
      2.99; 95% CI, 1.04-8.62), or back or neck problems (AOR, 1.51; 95% CI, 1.02
      2.23). Factors independently associated with frequent use (. or = 8 visits per
      year) of a CAM provider were full insurance coverage of the CAM provider (AOR,
      5.06; 95% CI, 2.45-10.47), partial insurance coverage (AOR, 3.26; 95% CI, 1.72
      6.19), having used the therapy for wellness (AOR, 2.85; 95% CI, 1.63-4.98), and
      having seen the provider for back or neck problems (AOR, 2.26; 95% CI, 1.29
      3.94). Conservative extrapolation to national estimates suggests that 8.9% of the
      population (17.5 million adults) accounted for more than 75% of the 629 million
      visits made to CAM providers in 1997. CONCLUSIONS: A small minority of persons
      accounted for more than 75% of visits to CAM providers. Extent of insurance
      coverage for CAM providers and use for wellness are strong correlates of frequent
      use of CAM providers.

PMID- 11822922
TI  - Cigarette yield and the risk of myocardial infarction in smokers.
AB  - BACKGROUND: Although cigarette smoking is a major risk factor for acute
      myocardial infarction (MI), cigarette tar yield has not been clearly demonstrated
      to affect MI risk. METHODS: A case-control study of first MI in smokers aged 30
      through 65 years was conducted among 68 hospitals in an 8-county area during a 28
      month period. Case subjects were smokers hospitalized at any of the area
      hospitals with a first MI. Approximately 4 community control smokers per case
      subject were randomly selected from the same geographic area using random digit
      dialing. Detailed data on smoking history and cigarette brand were collected.
      RESULTS: We identified 587 case subjects and 2685 controls who smoked cigarettes
      with known tar yields. After adjustment using multivariable logistic regression,
      the odds ratios (ORs) for subjects smoking medium- and high compared with low-tar
      yield cigarettes were 1.86 (95% confidence interval [CI], 1.21-2.87) and 2.21
      (95% CI, 1.47-3.34), respectively. The adjusted OR increased as tar per day
      intake increased (P<.001 for the trend); compared with the lowest category of tar
      per day, the ORs (95% CIs) for increasing tar per day were 1.16 (0.83-1.62), 1.85
      (1.35-2.52), 2.42 (1.54-3.78), and 2.50 (1.78-3.52). There was a similar trend of
      increasing ORs as tar per day increased in smokers of lower-yield cigarettes
      (P<.001 for the trend) and when low-yield cigarette smokers were excluded (P<.001
      for the trend). CONCLUSIONS: Smoking higher-yield cigarettes is associated with
      an increased risk of MI, and there is a dose-response relationship between total
      tar consumption per day and MI.

PMID- 11822921
TI  - Effects of hyaluronate sodium on pain and physical functioning in osteoarthritis
      of the knee: a randomized, double-blind, placebo-controlled clinical trial.
AB  - BACKGROUND: Intra-articular hyaluronate sodium is a relatively new therapy for
      the treatment of osteoarthritis of the knee. This randomized, double-blind
      clinical trial was conducted at a large primary care medical center to determine
      the impact of hyaluronate sodium vs conventional therapy on measures of pain,
      stiffness, and disability at rest and following functionally relevant walking and
      stepping activities. METHODS: A total of 120 patients (mean age, 67 years) with
      unilateral grades 1 to 3 medial compartment knee osteoarthritis were randomized
      to 1 of 4 treatment groups: group 1, 2 mL of hyaluronate sodium at a
      concentration of 10 mg/mL and placebo (100 mg of lactose); group 2, nonsteroidal
      anti-inflammatory drugs (NSAIDs) (75 mg of diclofenac and 200 microg of
      misoprostol) and hyaluronate sodium; group 3, NSAIDs and placebo (2 mL of
      isotonic sodium chloride solution [saline]); and group 4, placebo (lactose and
      saline). Intra-articular hyaluronate sodium or saline (2 mL) was administered
      once weekly over 3 weeks while NSAIDs or lactose were administered twice daily
      over 12 weeks. MAIN OUTCOME MEASURES: (1) Western Ontario McMaster Universities
      Index (WOMAC) global measure of pain, stiffness, and disability; (2) visual
      analog scale (VAS) scores for pain at rest and following functional walking and
      stepping activities (self-paced walking and stepping); and (3) functional
      performance (exercise time, heart rate, and predicted maximum oxygen uptake) at
      baseline and weeks 4 and 12. RESULTS: At week 4, significant improvement in WOMAC
      scores for pain and disability and VAS score for resting pain was observed in
      groups 1 to 3 compared with baseline measures. Groups 1 and 2 showed
      significantly lower self-paced stepping pain, while no change was observed in
      group 4. At week 12, groups 1 to 3 showed significantly greater improvement in
      WOMAC pain subscale score and VAS score for resting pain; however, these
      differences did not vary from week 4. Following self-paced walking and stepping,
      groups 1 and 2 reported significantly less activity pain, while group 1 showed
      significantly faster self-paced walking and stepping test results. Groups 1 to 3
      improved self-paced walking and stepping time at week 12 compared with baseline
      measures, while predicted maximum oxygen uptake was significantly higher in the
      hyaluronate sodium groups 1 and 2 at weeks 4 and 12 compared with baseline
      measures. CONCLUSIONS: For resting pain relief, hyaluronate sodium seems to be as
      effective as NSAIDs. Further, for pain with physical activity and functional
      performance, hyaluronate sodium may be superior to placebo alone or NSAIDs alone.

PMID- 11822924
TI  - Expert agreement in Current Procedural Terminology evaluation and management
      coding.
AB  - BACKGROUND: Available data suggest that physicians are accurate in approximately
      55% of Current Procedural Terminology (CPT) evaluation and management (E/M)
      coding for their services. This accuracy is relative to observers' or auditors'
      assigned codes for these services, a group that has not been studied for their
      consistency in application of the CPT E/M coding guidelines. The purpose of this
      study was to determine the level of agreement of certified coding specialists in
      their application of CPT E/M coding guidelines. METHODS: Three hundred certified
      professional coding specialists randomly selected from the active membership of
      the American Health Information Management Association were sent 6 hypothetical
      progress notes of office visits along with a demographic survey. The study group
      assigned CPT E/M codes to each of the progress notes and completed the
      demographic survey. RESULTS: Coding specialists agreed on the CPT E/M codes for
      57% of these 6 cases. The level of agreement for the individual cases ranged from
      50% to 71%. Relative to the most common or consensus code, undercoding of
      established patients occurred more commonly than overcoding. In contrast, for new
      patient progress notes, overcoding relative to the consensus code was more common
      than undercoding. CONCLUSIONS: There is substantial disagreement among coding
      specialists in application of the CPT E/M coding guidelines. The results of this
      study are similar to results of prior studies assessing physician coding
      accuracy, suggesting that the CPT coding guidelines are too complex and
      subjective to be applied consistently by coding specialists or physicians.

PMID- 11822923
TI  - Chronic work stress and marital dissolution increase risk of posttrial mortality
      in men from the Multiple Risk Factor Intervention Trial.
AB  - BACKGROUND: Acute life stressors can trigger premature death, but the role of
      more enduring, chronic stressors is less clear. We evaluated men's mortality risk
      associated with number of different work stressors and marital dissolution during
      the Multiple Risk Factor Intervention Trial (MRFIT). METHODS: Men without
      definite evidence of coronary heart disease (CHD) at study entry but with above
      average risk for CHD mortality based on blood pressure, serum cholesterol levels,
      and/or cigarette smoking were recruited into MRFIT. Survivors at the end of the
      trial were followed up for mortality for an additional 9 years. All 12,336
      survivors who completed the work-event checklist at the annual evaluations during
      the trial were included in the analyses of work stressors, whereas the 10,904 who
      were married at the start of the trial were included in the analyses of marital
      dissolution. RESULTS: Increasing number of different work stressors and divorce
      during the trial were associated with total and cardiovascular mortality during
      the 9-year follow-up period (Ps<.01 for linear trend), with a relative risk of
      1.26 (95% confidence interval, 1.07-1.48) for those reporting 3 or more different
      work stressors compared with those reporting none, and relative risk of 1.37 (95%
      confidence interval, 1.09-1.72) for those who divorced compared with those who
      remained married for total mortality. Analyses were adjusted for age,
      intervention group, educational attainment, occurrence of a nonfatal
      cardiovascular event during the trial, smoking, diastolic blood pressure, alcohol
      consumption, and serum cholesterol level (the last 4 adjustments were trial
      averages). CONCLUSION: Work and marital stressors increase risk for mortality in
      men.

PMID- 11822925
TI  - Dilutional hyponatremia in patients with cirrhosis and ascites.
AB  - OBJECTIVES: To analyze the predisposing factors, modifications of vasoactive
      systems, and prognosis of patients with cirrhosis and hyponatremia. PATIENTS AND
      METHODS: Fifty-four patients with hyponatremia (serum sodium level of <130 mEq/L
      after 5 days of hyponatremic diet and no diuretic therapy). Twenty cirrhotic
      patients served as controls. We measured plasma renin activity and levels of
      plasma aldosterone, norepinephrine, and antidiuretic hormone. Follow-up
      identified the development of hepatorenal syndrome and death. RESULTS: A higher
      percentage of patients with hyponatremia had decreased liver size, higher levels
      of plasma renin activity, and higher serum concentrations of aldosterone and
      norepinephrine. Renal insufficiency was detected in 31 of them (57%).
      Precipitating factors (hemorrhage or infections) were detected in 27 patients
      (50%). Incidence of hepatorenal syndrome and death were higher in patients with
      spontaneous development of hyponatremia (n = 23 [85%] and n = 25 [93%],
      respectively) than in patients with precipitating factors (n = 15 [56%] and n =
      12 [44%], respectively) and cirrhotic controls (n = 1 [5%] and n = 5 [25%],
      respectively) (P<.001). Results of multivariate analysis showed that Child-Pugh
      index, presence of hepatocarcinoma, and serum concentration of urea were
      associated with mortality. After excluding those patients with kidney failure at
      the time of admission, only Child-Pugh index and norepinephrine concentrations
      were independent predictors of mortality. CONCLUSIONS: Hyponatremia is an
      alteration in patients with advanced liver disease. Although survival is
      significantly reduced in patients with spontaneous development of hyponatremia, a
      reduced sodium concentration cannot be considered as a independent predictor of
      the risk for death.

PMID- 11822926
TI  - Prevention of contrast media-associated nephropathy: randomized comparison of 2
      hydration regimens in 1620 patients undergoing coronary angioplasty.
AB  - BACKGROUND: The administration of radiographic contrast agents remains an
      important cause of acute renal failure. The optimal infusion for hydration has
      not been evaluated. OBJECTIVE: To compare the incidence of contrast media
      associated nephrotoxicity with isotonic or half-isotonic hydration. DESIGN:
      Prospective, randomized, controlled, open-label study. METHODS: Patients
      scheduled for elective or emergency coronary angioplasty were randomly assigned
      to receive isotonic (0.9% saline) or half-isotonic (0.45% sodium chloride plus 5%
      glucose) hydration beginning the morning of the procedure for elective
      interventions and immediately before emergency interventions. An increase in
      serum creatinine of at least 0.5 mg/dL (44 micromol/L) within 48 hours was
      defined as contrast media-associated nephrotoxicity. Secondary end points were
      cardiac and peripheral vascular complications. RESULTS: A total of 1620 patients
      were assigned to receive isotonic (n = 809) or half-isotonic (n = 811) hydration.
      Primary end point analysis was possible in 1383 patients. Baseline
      characteristics were well matched. Contrast media-associated nephropathy was
      significantly reduced with isotonic (0.7%, 95% confidence interval, 0.1%-1.4%) vs
      half-isotonic (2.0%, 95% confidence interval, 1.0%-3.1%) hydration (P =.04).
      Three predefined subgroups benefited in particular from isotonic hydration:
      women, persons with diabetes, and patients receiving 250 mL or more of contrast.
      The incidence of cardiac (isotonic, 5.3% vs half-isotonic, 6.4%; P =.59) and
      peripheral vascular (isotonic, 1.6% vs half-isotonic, 1.5%, P =.93) complications
      was similar between the 2 hydration groups. CONCLUSION: Isotonic hydration is
      superior to half-isotonic hydration in the prevention of contrast media
      associated nephropathy.

PMID- 11822927
TI  - Levothyroxine treatment and occurrence of fracture of the hip.
AB  - BACKGROUND: Levothyroxine sodium is widely prescribed and has been implicated as
      a cause of reduction in bone mineral density and, therefore, suggested to be a
      major contributor to the risk of osteoporotic fractures. OBJECTIVE: To
      investigate whether levothyroxine use increases the risk of developing
      osteoporotic fractures. METHODS: We conducted a population-based, case-control
      analysis of the risk of a femur fracture in a large cohort of patients who had
      been prescribed levothyroxine. We used the United Kingdom General Practice
      (primary care) Research Database to identify 23,183 patients who had been
      prescribed long-term thyroid hormone therapy and to identify for each patient
      taking levothyroxine 4 controls matched for age, sex, primary care practice, and
      duration of registration on the database. The number of patients who had
      sustained a fracture of the proximal femur was ascertained for each group,
      together with drug therapies and medical diagnoses likely to affect fracture
      risk. RESULTS: Of the 23,183 patients prescribed thyroid hormone, a mean +/- SE
      of 1.61% +/- 0.08% had sustained a fracture of the femur, compared with 1.44% +/-
      0.04% of 92,732 controls (P =.06). When analyzed according to sex, a significant
      difference in rate of fracture between patients taking levothyroxine and controls
      was found in males (P =.008). Compared with controls, patients taking
      levothyroxine had higher reported rates of medical diagnoses and therapies,
      potentially confounding the fracture risk. Independent predictors of the
      occurrence of fracture after adjustment for other factors were age (adjusted odds
      ratio [AOR], 1.11; 95% confidence interval [CI], 1.10-1.11; P<.001), medical
      diagnoses including rheumatoid arthritis (AOR in females, 1.69; 95% CI, 1.27
      2.26; P<.001), excessive use of alcohol (AOR in females, 3.05; 95% CI, 1.94-4.76;
      P<.001), and prescription of drugs (eg, anticonvulsants; AOR in females, 2.49;
      95% CI, 2.00-3.09; P<.001). Prescription of levothyroxine was an independent
      predictor of fracture occurrence in males (AOR, 1.69; 95% CI, 1.12-2.56; P =.01)
      but not females (AOR, 1.03; 95% CI, 0.92-1.16; P =.60). CONCLUSIONS: The lack of
      association between fracture and levothyroxine prescription in the whole cohort
      is reassuring, although an independent association between levothyroxine
      prescription and fracture occurrence in male patients suggests that levothyroxine
      may contribute to fracture risk in this specific group.

PMID- 11822928
TI  - Hepatitis C virus transmission from an anesthesiologist to a patient.
AB  - BACKGROUND: An anesthesiologist was diagnosed as having acute hepatitis C 3 days
      after providing anesthesia during the thoracotomy of a 64-year-old man (patient
      A). Eight weeks later, patient A was diagnosed as having acute hepatitis C.
      METHODS: We performed tests for antibody to hepatitis C virus (HCV) on serum
      samples from the thoracotomy surgical team and from surgical patients at the 2
      hospitals where the anesthesiologist worked before and after his illness. We
      determined the genetic relatedness of the HCV isolates by sequencing the
      quasispecies from hypervariable region 1. RESULTS: Of the surgical team members,
      only the anesthesiologist was positive for antibody to HCV. Of the 348 surgical
      patients treated by him and tested, 6 were positive for antibody to HCV. Of these
      6 patients, isolates from 2 (patients A and B) were the same genotype (1a) as
      that of the anesthesiologist. The quasispecies sequences of these 3 isolates
      clustered with nucleotide identity of 97.8% to 100.0%. Patient B was positive for
      antibody to HCV before her surgery 9 weeks before the anesthesiologist's illness
      onset. The anesthesiologist did not perform any exposure-prone invasive
      procedures, and no breaks in technique or incidents were reported. He denied risk
      factors for HCV. CONCLUSIONS: Our investigation suggests that the
      anesthesiologist acquired HCV infection from patient B and transmitted HCV to
      patient A. No further transmission was identified. Although we did not establish
      how transmission occurred in this instance, the one previous report of bloodborne
      pathogen transmission to patients from an anesthesiologist involved reuse of
      needles for self-injection.

PMID- 11822929
TI  - Cutaneous leukocytoclastic vasculitis and encephalitis associated with Mycoplasma
      pneumoniae infection.

PMID- 11822930
TI  - Periconceptional exposure to efavirenz and neural tube defects.

PMID- 11822931
TI  - Efavirenz-induced leukocytoclastic vasculitis.

PMID- 11822932
TI  - Modified serum albumin in the pathogenesis of glomerular diseases: a new
      hypothesis.

PMID- 11822933
TI  - Acute dystonia due to metoclopramide: increased risk in AIDS.

PMID- 11822934
TI  - Acute fulminant hepatitis after treatment with rabeprazole and terbinafine: is
      rabeprazole the culprit?

PMID- 11822936
TI  - Physical activity and cognitive decline in elderly persons.

PMID- 11822938
TI  - Recognition and clinical management of depression in congestive heart failure.

PMID- 11822939
TI  - Depression and major outcomes in older patients with heart failure.

PMID- 11822941
TI  - Hope for hops?

PMID- 11822943
TI  - Functional chest pain of presumed esophageal origin.

PMID- 11822945
TI  - Predictive factors associated with the development of abdominal compartment
      syndrome in the surgical intensive care unit.
AB  - HYPOTHESIS: Intraoperative and postoperative variables contribute to the
      development of abdominal compartment syndrome (ACS) in general surgical patients.
      DESIGN: Case-control cohort study of 44 patients admitted to the surgical
      intensive care unit from March 1, 1995, to January 1, 2001. Groups were matched
      with respect to age, sex, diagnosis, and procedure. Prospectively collected data
      included demographics, ventilatory parameters, fluid requirements, hemodynamic
      and oxygen-derived variables, length of stay, and mortality rates. Statistical
      analysis was done with the Fisher exact test and/or chi(2) analysis. Continuous
      variables were analyzed with multivariate and univariate analysis. Data are
      presented as mean +/- SD. Statistical significance is defined as P<.05. SETTING:
      Long Island Jewish Medical Center (New Hyde Park, NY) is a large tertiary
      teaching hospital. PATIENTS: Twenty-two patients admitted to the surgical
      intensive care unit who developed ACS, and 22 case-control patients without ACS.
      MAIN OUTCOME MEASURES: Identification of variables that predict the development
      of ACS. RESULTS: Twenty-two patients with episodes of ACS (group 1) were examined
      and contrasted with 22 matched patients without ACS (group 2). Using univariate
      analysis, the groups differed with respect to 24-hour fluid administration and
      balance, number of emergency procedures, peak airway pressure, central venous
      pressure, pulmonary artery occlusion pressure, lengths of stay in the hospital
      and intensive care unit, and mortality rates. With multivariate analysis, only 24
      hour fluid balance and peak airway pressure (group 1 vs group 2: mean +/- SD,
      15.9 +/- 10.3 L vs 7.0 +/- 3.5 L, and 57.9 +/- 11.9 mm Hg vs 32.2 +/- 7.1 mm Hg,
      respectively; P<.05) remained significantly different. The groups did not differ
      with regard to age, cardiac index, operative blood loss, duration of surgery,
      intraoperative fluid input, or balance. A predictive equation for ACS development
      was created: P = 1/(1 +e(-z)), where z= -18.6763 + 0.1671 (peak airway pressure)
      + 0.0009 (fluid balance). CONCLUSION: The results of this study indicate that 24
      hour fluid balance and peak airway pressure are 2 independent variables
      predictive of the development of ACS in nontrauma surgical patients.

PMID- 11822946
TI  - The use of the harmonic scalpel vs conventional knot tying for vessel ligation in
      thyroid surgery.
AB  - HYPOTHESIS: The technique of thyroidectomy has undergone little change in several
      decades. The harmonic scalpel, using ultrasonic frictional heating to ligate
      vessels, is widely used in laparoscopic surgery, but there is little experience
      in open thyroidectomy. We hypothesized that the use of the harmonic scalpel could
      lead to a significant reduction in operative time as compared with knot tying in
      thyroid surgery. DESIGN: Retrospective case-controlled study. SETTING: Teaching
      institution. PATIENTS: One hundred seventy-one consecutive patients undergoing
      lobectomy or total thyroidectomy by one surgeon (A.E.S.). INTERVENTIONS: Eighty
      six patients underwent thyroid surgery with the conventional clamp-and-tie
      technique (lobectomy, n = 49; total thyroidectomy, n = 36) and 85 with the
      harmonic scalpel (lobectomy, n = 38; total thyroidectomy, n = 47). MAIN OUTCOME
      MEASURES: Demographics, pathological characteristics, thyroid size, operative
      time, blood loss, and complications using a 2-tailed t test, chi(2)test, and
      Wilcoxon rank sum test. RESULTS: The 2 groups were similar regarding age and sex.
      There were no intraoperative complications. Mean +/- SD thyroid size tended to be
      larger in the harmonic scalpel group for both lobectomy (5.1 +/- 2.6 cm vs 4.2 +/
      2.2 cm; P =.06) and total thyroidectomy specimens (6.3 +/- 3.8 cm vs 4.8 +/- 2.9
      cm; P =.08) compared with the conventional technique. Mean +/- SD operative time
      was shorter in the harmonic scalpel group compared with the conventional
      technique group for both lobectomy (89 +/- 20 minutes vs 115 +/- 25 minutes;
      P<.01) and total thyroidectomy (132 +/- 39 minutes vs 161 +/- 42 minutes; P<.01)
      procedures. There was no difference between the 2 techniques regarding the amount
      of blood loss for different procedures. There was no effect of tumor size on
      operative time (Pearson correlation factors: 0.14 for total, 0.21 for unilateral
      thyroidectomy). CONCLUSIONS: The use of the harmonic scalpel for the control of
      thyroid vessels during thyroid surgery is safe, and it shortens the operative
      time by almost 30 minutes compared with the conventional technique for both
      unilateral lobectomy or total thyroidectomy procedures.

PMID- 11822947
TI  - Simultaneous gastrointestinal surgery in patients with elective abdominal aortic
      reconstruction: an additional risk factor?
AB  - HYPOTHESIS: The management of simultaneously occurring intra-abdominal
      abnormalities and abdominal aortic aneurysms or aortoiliac occlusive disease is
      controversial. The aim of this retrospective study was to analyze whether
      gastrointestinal operations performed at the same time as aortic repair increase
      the postoperative morbidity and mortality rate. METHOD: Between January 1, 1989,
      and December 31, 1997, a total of 42 patients underwent open aortic tube (n = 33)
      or bifurcated grafting (n = 9) and simultaneous surgery of 1 or more
      gastrointestinal abnormalities. In a matched-pairs analysis for each of the
      aforementioned patients, a control patient with an exclusive aortic procedure was
      selected. For each matched pair the following aspects were noted: the type of
      operative procedure, time of execution, duration of the surgical procedure, the
      duration of postoperative ventilatory assistance, intensive care unit and
      hospital stays, the number of blood units transfused, the use of antibiotics, and
      the main postoperative complications. RESULTS: The comparison between the matched
      pairs revealed no statistically significant difference for postoperative
      morbidity or mortality rate or length of intensive care unit and hospital stays.
      There were no operative or hospital deaths. None of the patients has (median
      follow-up, 68 months) shown evidence of graft infection. CONCLUSION: A 1-stage
      operation management is feasible if appropriate care is given to the technical
      details and if the rules of antisepsis are followed.

PMID- 11822951
TI  - Symptomatic nonparasitic hepatic cysts: options for and results of surgical
      management.
AB  - BACKGROUND: Management options for symptomatic nonparasitic hepatic cysts (SNHC)
      lack verification through comparative studies with respect to safety and long
      term effectiveness. HYPOTHESIS: Open cystectomy is the treatment of choice for
      patients with SNHC. SETTING: University hospital department of surgery. PATIENTS:
      Data were retrospectively analyzed from the clinical charts of 34 patients (26
      women and 8 men) undergoing surgery for SNHC from January 1, 1975, through
      January 1, 1999. Charts were obtained from the original hospital referral. MAIN
      OUTCOME MEASURES: Morbidity rates and long-term recurrence. We considered the
      following variables for analysis: age, sex, hepatic cyst location, diameter of
      the cyst at primary surgery, symptoms, surgical procedure, postoperative
      morbidity and mortality, length of postoperative hospital stay, and long-term
      outcome. RESULTS: The 34 patients underwent 47 operations for SNHC (mean
      diameter, 15.0 cm), with a mean follow-up of 50.0 months. Ten patients underwent
      open and 8, laparoscopic deroofing of the cyst. Enucleation of the cyst and
      hepatic resections were performed as primary procedures in 4 and 2 patients,
      respectively, and as secondary procedures in 6 and 7 patients, respectively. Two
      recurrences (25%) were found after laparoscopic deroofing and 3 (30%) after open
      deroofing. Two (50%) and 6 (100%) recurrences were found after cystojejunostomy
      and needle aspiration, respectively. No symptomatic recurrences occurred after 10
      cystectomies and 9 hepatectomies. One operative death (3%) occurred; however,
      morbidity rates were 18% (6/34) and 15% (2/13) after primary and secondary
      surgery, respectively. CONCLUSIONS: These results support our policy of
      performing open radical procedures in the treatment of SNHC; cystectomy is
      performed for primary surgery and hepatic resections for recurrences and
      complications. Conservative procedures have shown higher rates of recurrence and
      the need for further surgery. Only further technological improvements will allow
      a systematic and safe use of laparoscopy for radical surgery for SNHC.

PMID- 11822950
TI  - Indication and procedure for treatment of hepatolithiasis.
AB  - HYPOTHESIS: Because of its complicated clinicopathologic features,
      hepatolithiasis is difficult to treat, and there is no established method of
      treating patients with intrahepatic stones. DESIGN: Retrospective case-control
      study. SETTING: Second Department of Surgery, Wakayama Medical University, School
      of Medicine, Wakayama, Japan (January 1, 1971-December 31, 2000). PATIENTS:
      Eighty-nine patients treated for hepatolithiasis (43 male; median age, 56.9
      years). MAIN OUTCOME MEASURES: The rate of residual stones and complications
      after the treatments of hepatolithiasis. RESULTS: Between 1971 and 1985, 17
      patients (41%) had stones located in the left or right intrahepatic duct, and 25
      patients (60%) had stones located in the bilateral intrahepatic duct. From 1986
      through 2000, 32 patients (68%) had stones located in the left or right
      intrahepatic duct, and 15 patients (32%) had stones located in the bilateral
      intrahepatic duct (P =.009). The rate of residual stones after surgical and
      nonsurgical treatment was 41% (17 of 42 patients) in 1971 through 1985, but
      decreased to 11% (5 of 47 patients) in 1986 through 2000 (P =.001). The rate of
      residual stones after cholangioenterostomy or T-tube insertion was 43.8% (21 of
      48 patients), but the rate of residual stones after hepatectomy or percutaneous
      transhepatic cholangioscopic lithotripsy (PTCSL) was 2.4% (1 of 41 patients,
      P<.001). In cases treated by PTCSL, we used a holmium (Ho):YAG laser in 3 cases
      since 1999. To our knowledge, there have been no reports describing the use of
      Ho:YAG lasers to treat hepatolithiasis. Also, board-shaped stones can be
      sufficiently pulverized without inducing hemorrhage from the bile duct wall.
      CONCLUSIONS: According to the current therapeutic strategy for hepatolithiasis,
      hepatectomy seems to be the most effective treatment for selected patients with
      isolated left hepatolithiasis if other surgical procedures cannot remove all the
      related lesions. In addition, PTCSL seems to be performed first in isolated right
      hepatolithiasis and bilateral lobe type hepatolithiasis. In PTCSL procedures,
      favorable results have been obtained using the Ho:YAG laser for fracturing
      intrahepatic stones.

PMID- 11822952
TI  - Importance of cyst content in hydatid liver surgery.
AB  - HYPOTHESIS: Cyst content in hydatid liver surgery is a determinant of
      postoperative cavity-related complications. DESIGN: Cohort analytic study.
      SETTING: Referral public hospital. PATIENTS: Sixty-seven patients who had
      conservative surgery for hydatid liver disease were analyzed prospectively. Cysts
      were grouped as to the contents. Cysts containing bile and/or pus were considered
      complicated, whereas others were uncomplicated. After partial cystectomy,
      cavities were managed with external drainage, omentopexy, or introflexion,
      determined by the choice of the surgeons. MAIN OUTCOME MEASURES: Outcomes were
      measured by postoperative cavity-related complications, such as biliary leakage
      (leakage for 10 days or less), biliary fistula (leakage for more than 10 days),
      cavity infections, and postoperative hospitalization. RESULTS: Patient and cyst
      characteristics were comparable among the groups. External drainage technique had
      slightly more frequent cavity-related complications than omentopexy or
      introflexion (1.5-fold to 2-fold difference). More importantly, complications
      were significantly more frequent in the complicated cysts than in the
      uncomplicated cysts (7-fold to 30-fold difference). Mean postoperative
      hospitalization time for uncomplicated cysts was 6.5 days, and it was similar
      whether they were treated by external drainage, omentopexy, or introflexion (7.0,
      6.2, and 5.8 days, respectively). Mean postoperative hospitalization time for
      complicated cysts was longer than for uncomplicated cysts (17.5 days; P =.008).
      CONCLUSIONS: Uncomplicated cysts have lower complication rates and short hospital
      stay with each cavity management technique. Complicated cysts have higher
      complication rates and longer hospital stay regardless of the management
      technique. Therefore, complicated and uncomplicated cysts should be considered
      different forms of the disease and evaluated differently.

PMID- 11822953
TI  - The value of splenic preservation with distal pancreatectomy.
AB  - HYPOTHESIS: Splenic-preserving distal pancreatectomy for benign or low-grade
      malignant disease is associated with decreased perioperative morbidity compared
      with conventional distal pancreatectomy with splenectomy. DESIGN: A retrospective
      review of a prospective database of patients. SETTING: Memorial Sloan-Kettering
      Cancer Center, New York, NY. PATIENTS: All patients (N = 211) undergoing distal
      pancreatectomy. MAIN OUTCOME MEASURES: Perioperative complications, length of
      postoperative stay, and overall survival times were analyzed. RESULTS: After
      excluding patients with adenocarcinoma and those who had other major organ
      resection, 125 patients underwent distal pancreatectomy for benign or low-grade
      malignant disease with splenectomy (n = 79) or splenic preservation (n = 46).
      Perioperative complications occurred in 39 (49%) of the 79 patients following
      splenectomy and 18 (39%) of the 46 patients following splenic preservation (P
      =.21). Perioperative infectious complications and severe complications were
      significantly higher in the splenectomy group (28% and 11%) compared with the
      splenic preservation group (9% and 2%) (P =.01 and.05), respectively. Length of
      hospital stay was 9 days (range, 5-41 days) following splenectomy and 7 days
      (range, 5-26 days) following splenic preservation (P<.01). No difference in
      length of surgery, units of blood transfused, or perioperative mortality was
      noted between groups. CONCLUSIONS: Splenic preservation following distal
      pancreatectomy for benign or low-grade malignant disease is safe and is
      associated with a reduction in perioperative infectious complications, severe
      complications, and length of hospital stay compared with conventional distal
      pancreatectomy with splenectomy. Therefore, splenic preservation should be
      considered in this group of patients.

PMID- 11822954
TI  - Axillary padding as an alternative to closed suction drain for ambulatory
      axillary lymphadenectomy: a prospective cohort of 207 patients with early breast
      cancer.
AB  - HYPOTHESIS: Axillary lymphadenectomy performed without the use of a drain but
      with padding of the axilla is feasible and safe on an outpatient basis in the
      setting of conservative surgery for breast cancer. DESIGN: Prospective clinical
      study. SETTING: Public oncology center. PATIENTS: Two hundred seven patients were
      treated in our oncology center between January 11 and December 28, 1999, by means
      of this method of axillary lymphadenectomy based on axillary padding without a
      drain. One-day surgery was offered to each patient. INTERVENTION: At the end of
      each functional axillary lymphadenectomy, the axilla was padded with the use of
      axillary aponeurosis and local muscles. Axillary suction drains were not used at
      all in this series of patients. MAIN OUTCOME MEASURES: Prospective assessment was
      performed, without randomization, with regard to the length of hospital stay, the
      reasons for postoperative conversion from 1-day surgery to traditional
      hospitalization, and postoperative complications. RESULTS: Eighty-seven (42.0%)
      of the 207 patients underwent a 1-day procedure. In the 1-day surgery group, 87
      (84.5%) of the 103 patients benefited from a true 1-day surgery procedure. The
      main reasons for conversion were nausea and anxiety rather than surgical
      complications. Hospital stay never exceeded 3 days. The most common postoperative
      complication was axillary seroma, with an average incidence of 22.2%. CONCLUSION:
      Breast-preserving surgery with axillary lymphadenectomy and padding of the
      axilla, precluding the use of a drain, is feasible and safe on a 1-day surgery
      basis for selected consenting patients.

PMID- 11822956
TI  - Nutritional approach in malnourished surgical patients: a prospective randomized
      study.
AB  - HYPOTHESIS: Perioperative administration of a supplemented enteral formula may
      decrease postoperative morbidity. DESIGN: Randomized clinical trial. SETTING:
      Department of surgery at a university hospital. PATIENTS: One hundred ninety-six
      registered malnourished patients (weight loss > or = 10%) who were candidates for
      major elective surgery for malignancy of the gastrointestinal tract.
      INTERVENTION: After randomization (n = 150), one group received postoperative
      enteral feeding with a standard diet within 12 hours of surgery (control group; n
      = 50). Another group orally received 1 L/d for 7 consecutive days of a liquid
      diet enriched with arginine, omega-3 fatty acids, and RNA (preoperative group; n
      = 50). After surgery, patients were given the same standard enteral formula as
      the control group. A third group orally received 1 L/d for 7 consecutive days of
      the enriched liquid diet. After surgery, patients were given enteral feeding with
      the same enriched formula (perioperative group; n = 50). MAIN OUTCOME MEASURES:
      Postoperative complications and length of hospital stay. RESULTS: The 3 groups
      were comparable for baseline demographics, biochemical markers, comorbidity
      factors, and surgical variables. The intent-to-treat analysis showed that the
      total number of patients with complications was 24 in the control group, 14 in
      the preoperative group, and 9 in the perioperative group (P =.02, control group
      vs perioperative group). Postoperative length of stay was significantly shorter
      in the preoperative (13.2 days) and perioperative (12.0 days) groups than in the
      control group (15.3 days) (P =.01 and P =.001, respectively, vs the control
      group). CONCLUSION: Perioperative immunonutrition seems to be the best approach
      to support malnourished patients with cancer.

PMID- 11822957
TI  - G protein gamma 7 expression as a new clinicopathological marker in patients with
      intrahepatic cholangiocarcinoma.
AB  - HYPOTHESIS: The signal alterations mediated by small G proteins such as Ras, Rho,
      and Rac have been reported in several cancers. The human G protein gamma 7 (G
      gamma 7) gene, which is down-regulated in various digestive organ cancers, was
      recently identified and cloned. Thus, the G-gamma 7-coupled heterotrimeric G
      proteins may also contribute to carcinogenesis in human cancers. SETTING:
      University hospital and medical institute of bioregulation. PATIENTS AND METHODS:
      The clinicopathological significance of G-gamma 7 expression in 18 patients with
      intrahepatic cholangiocarcinoma (IHCC) was examined. The tumor-nontumor ratio of
      G-gamma 7 expression was determined using reverse transcription polymerase chain
      reaction analysis. To visualize the localization of G-gamma 7, an
      immunohistochemical study was performed. MAIN OUTCOME MEASURE:
      Clinicopathological significance of G-gamma 7 expression in human IHCC. RESULTS:
      Expression of G-gamma 7 messenger RNA was lower in tumor tissue than in the
      corresponding nontumor tissue in 17 (94%) of 18 patients with IHCC. The mean
      tumor-nontumor ratio was 0.54. Eleven patients with tumor-nontumor ratios less
      than 0.5 showed significantly poorer differentiated IHCC than 7 with tumor
      nontumor ratios of 0.5 and greater (P<.01). Decreased expression of G-gamma 7
      protein in the carcinoma tissue, especially in the poorly differentiated IHCC
      tissue, was confirmed using immunohistochemical staining. CONCLUSIONS: Reduced
      expression of G-gamma 7 is associated with the histological grade of IHCC and may
      therefore prove to be a useful marker for predicting the biological
      aggressiveness of human IHCC.

PMID- 11822958
TI  - Measurement of intraoperative parathyroid hormone predicts long-term operative
      success.
AB  - HYPOTHESIS: A decrease in the intraoperative parathyroid hormone (PTH) level
      predicts long-term operative success. DESIGN: A case series of consecutive
      patients undergoing parathyroidectomy with intraoperative PTH measurement.
      SETTING: A university hospital. PATIENTS AND INTERVENTION: One hundred two
      patients with sporadic primary hyperparathyroidism underwent parathyroidectomy
      according to the principles of unilateral exploration with intraoperative PTH
      measurement. MAIN OUTCOME MEASURES: Longitudinal effects on levels of serum
      calcium and PTH. RESULTS: In 94 of 98 patients who underwent primary exploration
      because of a solitary adenoma, intraoperative PTH decreased at least 60% 15
      minutes after gland excision. The 4 cases in which PTH fell to less than 60% were
      classified as false negatives. Patients examined for multiglandular disease (n =
      4) were correctly predicted not to have an adenoma. Twenty-two patients (22%)
      were unavailable for 5-year follow-up. These patients were followed up for 2
      months to 48 months (median, 24 months), and none developed recurrent primary
      hyperparathyroidism. Of the remaining 80 patients (78%), all but 1 patient had
      normal or slightly decreased serum calcium levels (mean +/- SD, 9.24 +/- 0.4
      mg/dL [2.31 +/- 0.10 mmol/L]) at 5-year follow-up. One patient with hypercalcemia
      (10.6 mg/dL [2.65 mmol/L]) was interpreted to have developed renal failure with
      secondary hyperparathyroidism. Thirty-four patients had elevated serum PTH levels
      at least once during the postoperative study period, with normal or slightly
      decreased calcium concentrations. The prediction of late postoperative
      normocalcemia by means of intraoperative PTH measurement had an overall accuracy
      of 95%. CONCLUSIONS: The measurement of intraoperative PTH during surgery for
      primary hyperparathyroidism accurately differentiates between single- and
      multiple-gland disease and ensures good long-term results.

PMID- 11822959
TI  - The effect of laparoscopy on survival in pancreatic cancer.
AB  - HYPOTHESIS: Exposure to laparoscopy influences survival in patients with
      unresected pancreatic cancer who have a diagnostic or staging surgical procedure.
      METHODS: We used the Surveillance, Epidemiology, and End Results Medicare-linked
      database to identify a cohort of persons 65 years and older, who were newly
      diagnosed with primary pancreatic cancer between 1991 and 1996 and who had a
      diagnostic laparoscopy or laparotomy during the course of their disease. Patients
      with a prior malignancy and those who had a pancreatic resection were excluded.
      We used proportional-hazards regression to adjust risk estimates for demographic
      factors, medical comorbidities, tumor characteristics, and the use of other
      treatment modalities. RESULTS: We identified 112 individuals with pancreatic
      cancer who had a laparoscopic procedure and 791 who had only conventional
      surgery. More patients who had laparoscopic surgery had distant metastases at
      diagnosis (67.9% vs 41.2%; P =.001). Median duration of survival in the
      laparoscopic surgery group was 4.8 months (95% confidence interval [CI], 4.1-6.8)
      compared with 5.3 months in the group that had only open surgery (95% CI, 4.9
      5.6; P =.83). Compared with patients who only had a laparotomy, patients who had
      laparoscopic surgery did not have an increased rate of death when adjusted for
      the effects of age, sex, tumor size, grade, the presence of nodal and distant
      metastases at diagnosis, and the use of radiation, chemotherapy, therapeutic
      endoscopic retrograde cholangiopancreatography, and biliary and gastric bypass
      (adjusted hazard ratio, 0.93; 95% CI, 0.62-1.40). CONCLUSION: Exposure to
      laparoscopic surgery did not adversely affect survival in a cohort of elderly
      patients with pancreatic cancer who had a diagnostic procedure but no pancreatic
      resection.

PMID- 11822960
TI  - Posttraumatic stress, problem drinking, and functional outcomes after injury.
AB  - HYPOTHESIS: Patients undergoing trauma surgery for injury who have subsequent
      posttraumatic stress disorder (PTSD) or problem drinking will demonstrate
      significant impairments in functional outcomes compared with patients without
      these disorders. DESIGN: Prospective cohort study. SETTING: Level I academic
      trauma center. PARTICIPANTS: One hundred one randomly selected survivors of
      intentional and unintentional injuries were interviewed while hospitalized and
      again 1 year later. The investigation achieved a 73% 1-year follow-up rate. MAIN
      OUTCOME MEASURES: Posttraumatic stress disorder was assessed with the Post
      traumatic Stress Disorder Checklist and problem drinking was assessed with the
      Alcohol Use Disorder Identification Test. Functional status was assessed with the
      Medical Outcomes Study 36-Item Short-Form Health Survey. RESULTS: One year after
      injury, 30% of patients (n = 22) met symptomatic criteria for PTSD and 25% (n =
      18) had Alcohol Use Disorder Identification Test scores indicative of problem
      drinking. Patients with PTSD demonstrated significant adverse outcomes in 7 of
      the 8 domains of the Medical Outcomes Study 36-Item Short-Form Health Survey
      compared with patients without PTSD. In multivariate models that adjusted for
      injury severity, chronic medical conditions, age, sex, preinjury physical
      function, and alcohol use, PTSD remained the strongest predictor of an adverse
      outcome. Patients with problem drinking did not demonstrate clinically or
      statistically significant functional impairment compared with patients without
      problem drinking. CONCLUSIONS: Posttraumatic stress disorder persisted in 30% of
      patients 1 year after traumatic injury and was independently associated with a
      broad profile of functional impairment. The development of treatment intervention
      protocols for trauma patients with PTSD is warranted.

PMID- 11822962
TI  - Endovascular aortic aneurysm operations.
AB  - Options for the treatment of abdominal and thoracic aortic aneurysms are in a
      state of evolutionary change. The development and continued refinement of the
      endoluminal approaches has decreased the need for open aortic aneurysm surgery.
      Endovascular stent graft technology is an area of active research in which both
      the delivery systems and the endografts are undergoing continued improvement so
      that patients with what was previously thought to be unfavorable anatomy may be
      treated by these means. The design and deployment techniques of the currently
      available endografts, as well as those in clinical trials, are presented.

PMID- 11822961
TI  - Effect of preoperative radiochemotherapy on lymph node retrieval after resection
      of rectal cancer.
AB  - HYPOTHESIS: Preoperative radiochemotherapy for advanced rectal cancer results in
      fewer lymph nodes detected in the tumor-bearing specimen. DESIGN: Nonrandomized
      control trial with analysis of a prospective perioperative database. SETTING:
      Department of Surgery of a large-volume university hospital. PATIENTS: All
      patients who underwent conventional open surgery to cure rectal cancer between
      January 1, 1996, and March 31, 2001. INTERVENTIONS: During the study period 184
      patients (81%, control group) underwent surgery without receiving preoperative
      radiochemotherapy. Forty-two patients (19%, study group) who had advanced rectal
      cancer (modified Dukes stages B [tumors that have penetrated the muscle layer of
      the bowel wall or have gone through the bowel] or C [tumors that have spread to
      the lymph nodes in the same region]) received preoperative radiochemotherapy (2
      cycles of fluorouracil, 4500 rad) during this period. Most patients underwent
      anterior rectal resection in both groups (77.7% of those who did not receive
      preoperative radiochemotherapy and 71.8% of those who did), the remaining
      patients were treated with abdominoperineal resection. RESULTS: A mean (SEM) of
      19 (1) lymph nodes per specimen were detected in the control patients, while
      significantly fewer lymph nodes were detected in study patients (13 [1]; P<.05).
      The rate of inadequate lymph node staging (pNx) increased from 7% in the control
      group to 12% in the study group (P =.06). Pathological lymph node staging
      disclosed that significantly more study patients who received preoperative
      radiochemotherapy had modified Dukes stage A (tumors that are found only in the
      inner wall or rectum) cancer when compared with the control group (17% vs 0%,
      respectively; P<.05). CONCLUSIONS: Preoperative radiochemotherapy for advanced
      rectal cancer results in a significant decrease of lymph nodes detected within
      the tumor-bearing specimen. Preoperative radiochemotherapy induces significant
      downstaging with fewer positive lymph nodes and more patients presenting with
      Dukes stage A rectal cancer. Great care must be taken to remove an adequate
      number of lymph nodes and more sophisticated pathological techniques of lymph
      node detection are required since the tumors of ever-increasing numbers of
      patients are inadequately classified.

PMID- 11822963
TI  - Surgery in Austria.

PMID- 11822964
TI  - Image of the month. Heparin-induced thrombocytopenia: stop all heparin therapy
      and treat with lepirudin.

PMID- 11822965
TI  - Preferential laparoscopic live donor left nephrectomy in women of childbearing
      age.

PMID- 11822966
TI  - Comment on surgical anatomy.

PMID- 11822967
TI  - Chester Bidwell McVay, MD: the practicing anatomist.

PMID- 11822968
TI  - Zabdiel Boylston and the earliest published account of an elective surgical
      operation in colonial America.

PMID- 11822969
TI  - Vascular inflammation as a therapeutic target for prevention of cardiovascular
      disease.

PMID- 11822971
TI  - Atherosclerosis and inflammation.
AB  - The pathophysiology of coronary atherosclerosis is complex and multifactorial.
      The probability of the development of symptomatic coronary heart disease may be
      predicted by standard risk factor stratification involving hypertension,
      dyslipidemia, age, positive family history, and diabetes. However, risk factor
      stratification has been demonstrated to have significant limitations in the
      individual patient, which has generated a search for more specific and sensitive
      markers. Evidence is increasing that atherosclerosis is a disease characterized
      by inflammation, beginning with the earliest identifiable lesion (fatty streak)
      to the advanced vulnerable plaque. Clinical markers of inflammation, including C
      reactive protein, modified low-density lipoprotein, homocysteine, tumor necrosis
      factor, and thermogenicity, have been identified as emerging risk factors that
      may add prognostic information in patient management. This review centers on
      inflammation as a potential pathogenetic factor in atherosclerosis and the role
      that clinical markers may play in the identification of patients at risk.

PMID- 11822973
TI  - Alcohol: lipid metabolism and cardioprotection.
AB  - The decision to consume alcohol is associated with risks and benefits that vary
      according to family history (genes) and environment. The risk for coronary heart
      disease (CHD) is reduced in populations that regularly consume moderate amounts
      of alcohol. The risk reduction is associated with increased plasma high-density
      lipoprotein (HDL) cholesterol. Predisposing factors may make some individuals
      more vulnerable to alcohol-related risks than others. For example, individuals
      with hypertriglyceridemia and a personal or family history of pancreatitis might
      consider the benefits of alcohol consumption not worth the health risks. The
      risks might be more acceptable to someone with a family history of CHD, normal
      plasma triglyceride levels, low HDL cholesterol, and no personal or family
      history of addictive behavior or pancreatitis. An understanding of the metabolic
      effects of alcohol and a careful study of personal and family histories should
      permit physicians and their patients to make informed decisions about the risks
      and benefits of alcohol consumption.

PMID- 11822972
TI  - Statin therapy after acute myocardial infarction: are we adequately treating high
      risk patients?
AB  - After acute myocardial infarction, patients remain at high risk for recurrent
      cardiovascular events and mortality. Despite the compelling scientific and
      clinical trial evidence that lipid-lowering medications reduce mortality in
      patients after acute myocardial infarction, this life-saving therapy continues to
      be underutilized. A number of studies in a variety of clinical settings have
      documented that a significant proportion of patients after myocardial infarction
      are not receiving treatment with lipid-lowering medications when guided by
      conventional care. It has recently been demonstrated that implementation of a
      hospital-based system for initiation of statins prior to hospital discharge
      results in a marked increase in treatment rates, improved long-term patient
      compliance, more patients reaching low-density lipoprotein levels of less than
      100 mg/dL, and improved clinical outcomes. Adopting in-hospital initiation of
      lipid-lowering medications as the standard of care for patients hospitalized with
      acute myocardial infarction could dramatically improve treatment rates and thus
      substantially reduce the risk of future coronary events and prolong life in the
      large number of patients hospitalized each year.

PMID- 11822974
TI  - Chronic infections and atherosclerosis/thrombosis.
AB  - An emerging pathophysiologic paradigm implicates chronic inflammation in the
      initiation, progression, and destabilization of atherosclerotic vascular disease.
      Various potential contributors to the inflammatory response in the vessel wall
      include atherogenic lipids, mechanical stress and injury, hypertension and
      angiotensin II, cigarette smoking, immune response to neoantigens, and chronic
      infections with viruses and or bacteria (Table 1). The potential link between
      chronic infection and atherosclerosis/thrombosis is under extensive investigation
      in several laboratories around the world. Although indirect evidence and
      experimental data tend to support this link, definitive proof is still lacking.
      If such a link is eventually proven to be causal in nature, it will provide a
      novel target for preventive and therapeutic strategies (anti-infective drugs,
      vaccines, etc.) against a common disease that is the leading killer of people in
      Western nations. Results of ongoing, large-scale clinical trials are eagerly
      awaited.

PMID- 11822975
TI  - Heart rate variability and cardiovascular mortality.
AB  - The autonomic nervous system plays a major role in affecting the cardiac milieu
      and promoting malignant ventricular activity. The measurement of heart rate
      variability (HRV) is a noninvasive tool for assessing the status of the autonomic
      nervous system. A depressed HRV among post-myocardial infarction patients is a
      well-established risk factor for arrhythmic death. A reduced HRV has also been
      used to identify diabetic patients with autonomic neuropathy. This paper presents
      recent developments in the use of HRV, focusing on further refinement and
      validation of the use of both linear and nonlinear dynamics for sudden death
      prognostication, evaluation of the effect of specific pharmacologic agents on
      HRV, and assessment of HRV in health and in specific disease states that have
      been associated with an increased mortality risk.

PMID- 11822976
TI  - Magnetic resonance imaging in detection and functional assessment of coronary
      artery disease.
AB  - The past few years have brought significant improvements in the field of
      cardiovascular magnetic resonance imaging (MRI), which evolved from an
      experimental technique to a clinically accepted method of coronary artery disease
      detection (stress MRI) and viability assessment. In this article, we describe
      current MRI technology for detection and functional assessment of ischemia, such
      as dobutamine/atropine MRI, perfusion techniques, viability, and flow reserve in
      native coronary arteries and grafts. With further refinement in the technology,
      wide acceptance of cardiovascular MRI is anticipated in clinical practice.

PMID- 11822977
TI  - Cardiovascular disease: much more aggressive in patients with type 2 diabetes.
AB  - It is estimated that 80% of individuals with type 2 diabetes die of coronary
      heart disease. Several factors have been found to contribute to the accelerated
      atherosclerosis present in diabetic patients. These include hyperglycemia-induced
      endothelial cell dysfunction, impaired fibrinolysis, increased platelet
      aggregation, and dysfunctional arterial remodeling. The evidence supports that a
      healthy lifestyle, statin drugs, angiotensin-converting enzyme inhibitors, and
      aspirin can modify these factors and slow the atherosclerosis process observed in
      type 2 diabetes. Because of the high prevalence of cardiovascular disease in
      people with type 2 diabetes, early cardiac testing is indicated. The optimal
      strategy for coronary revascularization in diabetic patients remains
      controversial and is discussed in detail in this review.

PMID- 11822978
TI  - Atherosclerosis, cigarette smoking, and endogenous fibrinolysis: is there a
      direct link?
AB  - Acute myocardial infarction is caused by thrombotic occlusion of a coronary
      artery at the site of a ruptured or eroded atheromatous plaque. The maintenance
      and regulation of tissue perfusion critically depend upon the integrity of
      endothelial function and the release of potent endothelium-derived factors, such
      as the fibrinolytic factor tissue plasminogen activator (tPA). Atherosclerosis
      and cigarette smoking are associated with dysfunction of the endothelium, and in
      particular, appear to impair the acute local endogenous fibrinolytic activity.
      This provides a potential mechanism whereby atherosclerosis and cigarette smoking
      can markedly influence the initiation, propagation, and resolution of the acute
      and chronic thrombotic complications of coronary artery disease through
      reductions in the capacity to release tPA acutely.

PMID- 11822979
TI  - Myocardial hibernation in coronary artery disease.
AB  - Coronary artery disease (CAD) is very prevalent in Western societies and is a
      leading cause of mortality and morbidity. Despite decreases in mortality rates
      from CAD over the past 30 years, ischemic heart failure remains an important
      problem because people with CAD are now living longer. Hibernating myocardium may
      be defined as reversible left ventricular dysfunction due to chronic CAD that
      shows improvement in function after revascularization. Many patients with
      ischemic cardiomyopathy have areas of hibernating myocardium, and thus can
      potentially show improvement in left ventricular regional and global function if
      they are revascularized. Whether hibernating myocardium represents an adaptive
      response to hypoperfusion in the face of chronic ischemia or whether it is a
      degenerative process is not entirely clear. Clearly, ultrastructural changes of
      de-differentiation are seen, and include loss of sarcomeres and the appearance of
      small mitochondria and glycogen accumulation. Although the mechanisms underlying
      the changes in morphology and depressed contractility, and the factors governing
      recovery of function are not clear, changes in adrenergic receptor density,
      cytokine upregulation, and the degree of fibrosis may all play a role.
      Identification of viability is commonly performed with dobutamine
      echocardiography or nuclear imaging. Because patients with extensive CAD and poor
      left ventricular systolic function are high-risk candidates for coronary bypass
      surgery, the preoperative identification of viability provides important
      prognostic information. Patients with viable myocardium who are treated with
      revascularization rather than medical therapy have better outcomes in terms of
      survival, left ventricular function, symptoms, and exercise capacity.

PMID- 11822981
TI  - Lung cancer--a changing picture.

PMID- 11822980
TI  - Hormone replacement therapy trials: an update.
AB  - Recent randomized trials of hormone replacement therapy (HRT) in postmenopausal
      women are not consistent with the decrease in cardiovascular risk seen in
      observational studies of hormone therapy users compared with nonusers. Emerging
      evidence indicates that HRT use in some women with established coronary heart
      disease may be associated with prothrombotic effects or proinflammatory effects
      leading to adverse events. In healthy women, the decision to use HRT should be
      based primarily on noncardiac factors until more data becomes available that is
      relevant to this population. Several alternatives to HRT, including
      phytoestrogens and selective estrogen receptor modulators, have favorable effects
      on cardiovascular risk factors, but their impact on clinical outcomes remains to
      be determined.

PMID- 11822982
TI  - Pediatric non-Hodgkin's lymphoma: clinical and biologic prognostic factors and
      risk allocation.
AB  - The use of effective combination chemotherapy for all stages and subtypes of non
      Hodgkin"s lymphoma (NHL) in children has resulted in a striking improvement in
      cure rates. Event-free survival now ranges from 70% to 90%, depending on the
      stage of disease and the NHL subtype. Risk-adapted therapy has resulted in a
      dramatic improvement in outcome for high-risk patients, at the cost of
      significantly increased short-term toxicity, and a reduction of therapy and
      toxicity for the lower-risk patient, while maintaining the excellent cure rate.
      Successful risk allocation of patients is dependent on the identification and
      continual validation of prognostic factors. The specific treatment protocol is
      the single most important factor predicting outcome today. Traditional prognostic
      factors such as stage and tumor burden are useful in selecting the intensity and
      length of therapy, rather than as a major indicator of likelihood of survival. In
      order to further improve cure rates and decrease toxicity, new biologic
      prognosticators need to be found and validated. Some promising avenues for study
      appear to be the presence or absence of adhesion molecules and of aberrant
      proteins that are specific to subtypes of lymphomas, such as soluble CD30 and
      anaplastic lymphoma kinase (ALK), the molecular classification of lymphomas on
      the basis of gene expression, and the evaluation of biologic markers for
      measuring early response to therapy.

PMID- 11822983
TI  - Risk assignment in childhood brain tumors: the emerging role of molecular and
      biologic classification.
AB  - Brain tumors as a group are the most common solid tumors of childhood and
      currently have the highest mortality rate. A major emphasis has historically been
      placed on stratifying therapy for these tumors based on histologic and clinical
      prognostic factors. However, with the increasing application of molecular
      approaches to refine the categorization of these tumors, it has become apparent
      that histologically comparable lesions may exhibit diverse patterns of gene
      expression and genomic alterations, which may correspond with important
      prognostic distinctions. This paper summarizes these observations and discusses
      how they are being applied in a preliminary fashion as a foundation for risk
      adapted stratification of childhood brain tumor therapy.

PMID- 11822985
TI  - Central nervous system-directed therapy in the treatment of childhood acute
      lymphoblastic leukemia and studies of neurobehavioral outcome: Children's Cancer
      Group trials.
AB  - Long-term survival rates in childhood acute lymphoblastic leukemia (ALL) have
      improved due, in part, to the introduction and subsequent refinements in central
      nervous system (CNS)-directed therapy. Studies of cognitive, motor, and
      behavioral functioning, which characterize the patterns and severity of CNS
      sequelae, are being used increasingly as measurable treatment endpoints. This
      paper summarizes the advances in CNS-directed therapy derived from Children's
      Cancer Group randomized therapeutic trials. Results from neurobehavioral outcome
      studies built upon these trials are also presented. A section of this review is
      focused on CNS-directed treatments and the neurodevelopmental outcomes of infants
      diagnosed with ALL, an especially high-risk patient subset. Future studies of
      neurobehavioral outcome are briefly elaborated in the context of current
      chemotherapy approaches used in the treatment of childhood ALL.

PMID- 11822984
TI  - Risk assignment in pediatric soft-tissue sarcomas: an evolving molecular
      classification.
AB  - Pediatric soft-tissue sarcomas are increasingly being defined by both histologic
      appearance and underlying chromosomal abnormalities to determine their biologic
      behavior. Most sarcomas of this type have specific chromosomal translocations
      that create unique fusion genes. Expression of such fusion genes may have
      diagnostic, prognostic, and surveillance implications for the patient. This
      review analyzes the fusion gene expressions seen with seven of the major types of
      pediatric soft-tissue tumors and their impact on biologic behavior. In nearly 50%
      of the malignancies discussed, the diagnostic, prognostic, and surveillance
      implications of their specific fusion gene expressions are already defined or
      becoming established (alveolar rhabdomyosarcoma, Ewing sarcoma/primitive
      neuroectodermal tumor, and synovial sarcoma). In the remainder of the tumors,
      these questions are rapidly being addressed. To facilitate future fusion gene
      studies, pediatric surgeons, pathologists, and oncologists need to work as a
      coordinated team to ensure proper tumor procurement. Large clinical cooperative
      trials involving biologic studies of pediatric soft-tissue sarcomas could
      facilitate advancement of knowledge in this area of pediatric oncology.

PMID- 11822986
TI  - The role of radical hysterectomy and neoadjuvant chemotherapy in carcinoma of the
      cervix.
AB  - The patient presenting with a bulky stage IB2 cervical cancer is a therapeutic
      challenge. None of the current surgical or radiation treatment strategies
      satisfactorily leads to a high rate of disease-free survival and a low risk of
      treatment-related complications including ovarian failure and psychosexual
      deficits. Neoadjuvant chemotherapy may allow for reductions in tumor bulk,
      thereby rendering radiation therapy more effective or surgery more feasible.
      Impressive clinical response rates to cisplatin-based neoadjuvant chemotherapy
      have been achieved with acceptable toxicity. Approximately 20% of patients
      achieve a complete clinical response, and many also experience a complete
      pathologic response. There are still too few comparative studies and phase III
      trials to assess the effectiveness of neoadjuvant chemotherapy and radical
      surgery relative to standard treatments.

PMID- 11822988
TI  - Second-line and subsequent therapy for ovarian carcinoma.
AB  - Ovarian carcinoma continues to be the leading cause of death among gynecologic
      malignancies. Paclitaxel and platinum chemotherapy is still the treatment of
      choice after primary debulking surgery. Salvage chemotherapy with several single
      agents has only modest activity and does not prolong survival of patients with
      relapsed ovarian carcinoma. An intense search has been made for novel approaches
      to treatment of ovarian cancer, and several new treatments, such as immunotherapy
      and gene therapy, show promise. Newer combination chemotherapy regimens and
      molecularly targeted therapy need to be developed. High-dose chemotherapy with
      autologous stem-cell transplantation appears to benefit selected groups of
      patients and is still investigational. Whole abdominal radiotherapy for relapsed
      microscopic disease should be studied in prospective randomized trials. Women
      with advanced ovarian carcinoma should continue to be encouraged to participate
      in well-designed clinical trials.

PMID- 11822987
TI  - Hormone replacement therapy for survivors of breast and endometrial cancer.
AB  - Indirect evidence suggests that endogenous and exogenous estrogen does not
      influence the outcome of patients treated for breast or endometrial cancer.
      However, many reports have affirmed beneficial effects of hormone replacement
      therapy (HRT) in preventing multiple disease states and improving the quality of
      life of individual patients. Every practitioner of urogynecology understands the
      benefits of local and systemic therapy to women who suffer from urinary
      incontinence and/or loss of pelvic floor support. Thus, it seems appropriate to
      suggest that survivors of breast or endometrial cancer who request information on
      HRT for relief of their menopausal symptoms and for other benefits, of which
      patients are becoming increasingly aware, deserve a comprehensive explanation.

PMID- 11822990
TI  - Human papillomavirus in cervical cancer.
AB  - Epidemiologic studies supported by molecular technology have provided sufficient
      evidence of the causal role of some human papillomavirus (HPV) infections in the
      development of cervical cancer. The finding is consistent universally, and HPV
      has been proposed as the first identified necessary cause of cervical cancer.
      Such recognition translates into the concept that cervical cancer does not
      develop without persistent presence of HPV DNA. In the developed parts of the
      world, cytologic screening programs could benefit from the addition of HPV
      testing to their protocols. Controlled studies and one randomized trial have
      shown that HPV testing is helpful in solving the ambiguous cases generated by
      cytology reading. In populations where cytology programs are not functional or
      efficient, HPV testing is being evaluated as an alternative means of primary
      screening. Prevention of exposure to high-risk HPV types, either by prophylactic
      vaccination or by combined prophylactic and therapeutic immunologic intervention,
      may prove to be the most efficient and logistically feasible option for the
      prevention of cervical cancer in developing populations.

PMID- 11822989
TI  - Angiogenesis in ovarian cancer: molecular pathology and therapeutic strategies.
AB  - Ovarian cancer claims the lives of more women in North America each year than all
      other gynecologic malignancies combined. Despite the high initial response rates
      of patients with advanced ovarian cancer to aggressive primary surgical debulking
      followed by combination chemotherapy, the majority of patients will ultimately
      develop disease recurrence. The high risk of relapse and nearly guaranteed
      incurability after relapse is due to genetic instability and a high mutation rate
      of neoplastic cells that together allow for a high risk of selection for drug
      resistance. Given the seemingly insurmountable obstacle that acquired drug
      resistance presents in a setting of minimal, often undetectable, residual tumor
      burden in women with ovarian cancer, antiangiogenic-targeted therapies offer an
      attractive strategy for enhanced long-term disease-free survival. The past decade
      has witnessed a substantial proliferation in our knowledge regarding tumor
      angiogenesis, which has spurred interest in antiangiogenesis drug development.
      Current clinical trials are evaluating these agents in a variety of solid tumors,
      including ovarian cancer. Preliminary work has provided hope that the addition of
      antiangiogenic therapies may be incorporated into the treatment of women
      afflicted with ovarian cancer and may translate into enhanced survival.

PMID- 11822991
TI  - Does psychosocial functioning improve independent of depressive symptoms? A
      comparison of nefazodone, psychotherapy, and their combination.
AB  - BACKGROUND: Although it is known that antidepressant treatment improves
      psychosocial functioning, whether such changes occur independent of depressive
      symptoms is not known. This study compared efficacy of nefazodone, psychotherapy,
      and their combination in improving psychosocial functioning in chronically
      depressed outpatients. METHODS: Patients with chronic forms of major depressive
      disorder were randomized to 12 weeks of nefazodone, Cognitive Behavioral Analysis
      System of Psychotherapy (CBASP), or combined nefazodone/CBASP. Psychosocial
      assessments measured overall psychosocial functioning, work functioning,
      interpersonal functioning, and general health. RESULTS: Relative to community
      norms, patients with chronic major depression evidenced substantially impaired
      psychosocial functioning at baseline. Combined treatment produced significantly
      greater psychosocial improvement than either CBASP alone or nefazodone alone on
      all primary measures. Combined treatment remained superior to nefazodone on
      primary measures of work, social, and overall functioning, and superior to CBASP
      on social functioning when depressive symptoms were controlled. Unlike the two
      groups receiving nefazodone, CBASP alone's effect on psychosocial function was
      relatively independent of symptom change. Psychosocial functioning improved more
      slowly than depressive symptoms, and moderate psychosocial impairments remained
      at end point. CONCLUSIONS: Combined treatment had greater effect than either
      monotherapy. Change in depressive symptoms did not fully explain psychosocial
      improvement. Moderate residual psychosocial impairment remained, suggesting the
      need for continuation/maintenance treatment.

PMID- 11822992
TI  - Decreased gray matter concentration in the insular, orbitofrontal, cingulate, and
      temporal cortices of cocaine patients.
AB  - BACKGROUND: Structural deficiencies within limbic and prefrontal regions may
      contribute to the characteristic drug-seeking and drug-taking behaviors that
      prevail in persons dependent on cocaine. To date, a focal structural analysis of
      the brains of cocaine patients has not been undertaken. METHODS: We used voxel
      based morphometry in conjunction with statistical parametric mapping on the
      structural magnetic resonance images of cocaine-dependent (n = 13) and cocaine
      naive individuals (n = 16) to assess differences between the two groups in gray
      and white matter concentration. RESULTS: We report a decrease in gray matter
      concentration in the ventromedial orbitofrontal, anterior cingulate,
      anteroventral insular, and superior temporal cortices of cocaine patients in
      comparison to controls (p <.01 corrected for multiple comparisons). The average
      percentage decrease in gray matter concentration within a region ranged from 5%
      to 11%. White matter concentration did not differ between groups. CONCLUSIONS: We
      conclude that the brains of cocaine patients are structurally dissimilar from
      those of nondrug-using controls. The differences were detected in regions
      involved in decision-making, behavioral inhibition and assignation of emotional
      valence to environmental stimuli and, hence, may contribute to some of the
      behavioral deficits characteristic of chronic cocaine users.

PMID- 11822993
TI  - Sensitization to the cardiovascular but not subject-rated effects of oral cocaine
      in humans.
AB  - BACKGROUND: Despite a substantial nonhuman literature in the area, few studies
      have experimentally evaluated the effects of repeated stimulant administration in
      human participants. This study examined the effects of repeated cocaine in
      individuals with histories of abuse and dependence. METHODS: Twenty-two
      individuals with recent histories of cocaine abuse received under double-blind
      conditions, in pseudorandom order, four administrations of oral cocaine (150 mg
      [n = 14] or 200 mg [n = 8]) and two administrations of placebo. All
      administrations were given on separate days. Cardiovascular measures were
      collected and included heart rate, systolic pressure, diastolic pressure, mean
      arterial pressure, and pressure rate product. Subject-rated effects were assessed
      using the Addiction Research Center Inventory (ARCI) and a 15-item drug-effect
      questionnaire. RESULTS: There were significant differences between placebo days
      and cocaine days in both cardiovascular and subject-rated effects. Moreover,
      three of five cardiovascular measures analyzed revealed a significant main effect
      for day of cocaine administration. A planned follow-up contrast revealed a
      significant increasing linear trend for each of these variables across days. No
      significant effects were found for day of administration for the subject-rated
      items. CONCLUSIONS: These results indicate that, under controlled laboratory
      conditions, repeated oral cocaine administration may result in sensitization to
      the cardiovascular effects, but not subject-rated effects.

PMID- 11822994
TI  - Smoking, reward responsiveness, and response inhibition: tests of an incentive
      motivational model.
AB  - BACKGROUND: Incentive-motivation models of addiction suggest impairment of
      functional activity in mesocorticolimbic reward pathways during abstinence. This
      study tested implications for subjective and behavioral responses to nondrug
      incentives, cue-elicited craving, and prefrontal cognitive functions,
      particularly response inhibition. METHODS: We tested 26 smokers after smoking and
      after overnight abstinence in counterbalanced order; 26 nonsmokers were also
      tested twice. Measures included a simple card-sorting test performed with and
      without financial incentive (the CARROT), the Snaith Hamilton Pleasure Scale as
      an index of subjective reward responsiveness, ratings of subjective craving and
      withdrawal before and after exposure to a cigarette, an index of oculomotor
      response inhibition (saccadic vs. antisaccadic eye movements), verbal fluency,
      and reversed digit span. RESULTS: Compared with the smoking condition, and
      independently of withdrawal severity, abstinence was associated with reduced cue
      reactivity, pleasure expectancies, responsiveness to financial incentive, and
      response inhibition (antisaccadic eye movements). Verbal fluency and reversed
      digit span were unaffected, contrary to findings elsewhere with heavier smokers.
      Nonsmokers' scores either fell between those of abstainers and recent smokers or
      approximated those of recent smokers. CONCLUSIONS: The data were in general
      consistent with behavioral predictions derived from the incentive-motivational
      model of addiction and suggest that abstinence may be associated with impairments
      of motivation and response inhibition, which are independent of other
      subjectively experienced withdrawal symptoms.

PMID- 11822995
TI  - Effect of nicotine on quinpirole-induced checking behavior in rats: implications
      for obsessive-compulsive disorder.
AB  - BACKGROUND: Rats treated chronically in a large, open field with the dopamine
      D2/D3 receptor agonist quinpirole (QNP) develop compulsive checking behavior as
      defined by a set of behavioral criteria. This paradigm has been suggested as an
      animal model of obsessive-compulsive disorder (OCD). Because nicotine blocks
      various behaviors induced by ontogenetic QNP administration, we asked whether
      nicotine could attenuate QNP-induced compulsive checking. METHODS: Adult male
      Long-Evans rats (n = 14/group) were treated twice weekly with saline (control),
      or with QNP (0.5 mg/kg) for 14-16 injections. On the last two injections, rats
      were pretreated in random order with an acute dose of nicotine (0.3 mg/kg base)
      or saline 10 min before administration of QNP or saline; and the effects on
      checking behavior was examined. The effects of chronic QNP treatment on nicotinic
      receptors in discrete brain regions were also determined. RESULTS: Chronic QNP
      resulted in compulsive checking and increases in cerebellar alpha4beta2 and
      alpha7 nicotinic receptor densities. Nicotine pretreatment significantly reduced
      one of the three measures of compulsive checking behavior. CONCLUSIONS: Nicotine
      attenuates some symptoms of compulsive checking in a rat model of OCD; however,
      the mechanisms of this effect and therapeutic efficacy of nicotinic agonists in
      OCD require further study.

PMID- 11822996
TI  - Bulimic symptoms in the Virginia Twin Study of Adolescent Behavioral Development:
      correlates, comorbidity, and genetics.
AB  - BACKGROUND: This paper addresses bulimia symptoms in a large community sample of
      twins aged 8 to 17 years. We aim to identify environmental correlates of bulimia
      symptoms and relationships with other psychiatric disorder symptoms. The twin
      design allows examination of the structure of genetic and environmental effects.
      METHODS: DSM-IIIR bulimia symptoms and consequential impairment were measured by
      interview in the first wave of the Virginia Twin Study of Adolescent Behavioral
      Development. Comorbidity with other psychiatric symptoms and environmental
      correlates were examined and the relative contributions of genes and environment
      were assessed using structural equation modeling. RESULTS: An item-response
      theory model indicated that the range of bulimic symptoms represented a single
      underlying trait. Bulimia symptoms were more common in postmenarche girls and
      positively associated with body-mass index. Subdiagnostic symptomatology was
      associated with impairment in psychosocial functioning. Bulimia symptoms were
      strongly associated with other psychiatric disorders symptoms including anxiety
      and depression. Genetic model fitting identified strong additive genetic effects
      on the symptom score. Accounting for a potential violation of the equal
      environment assumption for identical and fraternal twins slightly reduced
      estimated genetic variance. CONCLUSIONS: The pattern of comorbidity suggests
      overlap between bulimia symptoms and those of internalizing disorders.
      Substantial genetic variance (44%) was evident in the most conservative model.

PMID- 11822997
TI  - A double-blind, placebo-controlled study of antidepressant augmentation with
      mirtazapine.
AB  - BACKGROUND: A previous pilot study of open-label mirtazapine augmentation
      conducted by the authors in 20 depressed patients yielded a 55% response rate at
      week 4. A double-blind controlled trial was undertaken to further elucidate the
      efficacy of this intervention. METHODS: 26 adult outpatients with persistent
      major depression despite adequate antidepressant monotherapy were randomized to
      receive 4 weeks of mirtazapine or placebo augmentation. Mirtazapine was begun at
      15 mg at bedtime, with possible titration to 30 mg at bedtime per physician's
      discretion after week 1. RESULTS: Categorical positive response rate at end point
      was 64% for active drug and 20% for placebo. Remission rates were 45.4% and 13.3%
      for active drug and placebo groups, respectively, Mirtazapine demonstrated
      statistically significant superiority to placebo on most major outcome measures,
      and was associated with improvement in overall functioning and quality of life.
      There were no significant group differences with regard to emergent side effects,
      weight change, or serum concentrations of primary antidepressants. CONCLUSIONS:
      Mirtazapine appears safe and effective for short-term antidepressant
      augmentation.

PMID- 11822998
TI  - Pilot study of secondary prevention of posttraumatic stress disorder with
      propranolol.
AB  - BACKGROUND: Preclinical considerations suggest that treatment with a beta
      adrenergic blocker following an acute psychologically traumatic event may reduce
      subsequent posttraumatic stress disorder (PTSD) symptoms. This pilot study
      addressed this hypothesis. METHODS: Patients were randomized to begin, within 6
      hours of the event, a 10-day course of double-blind propranolol (n = 18) versus
      placebo (n = 23) 40 mg four times daily. RESULTS: The mean (SD) 1-month Clinician
      Administered PTSD Scale (CAPS) score of 11 propranolol completers was 27.6
      (15.7), with one outlier 5.2 SDs above the others' mean, and of 20 placebo
      completers, 35.5 (21.5), t = 1.1, df = 29, p =.15. Two propranolol patients'
      scores fell above, and nine below, the placebo group's median, p =.03 (sign
      test). Zero of eight propranolol, but six of 14 placebo, patients were
      physiologic responders during script-driven imagery of the traumatic event when
      tested 3 months afterward, p =.04 (all p values one-tailed). CONCLUSIONS: These
      pilot results suggest that acute, posttrauma propranolol may have a preventive
      effect on subsequent PTSD.

PMID- 11823001
TI  - Metabolism of 2-hydroxy-4-methoxybenzophenone in isolated rat hepatocytes and
      xenoestrogenic effects of its metabolites on MCF-7 human breast cancer cells.
AB  - The metabolism and cytotoxicity of 2-hydroxy-4-methoxybenzophenone (HMB) in
      isolated rat hepatocytes and the xenoestrogenic activity of HMB and its
      metabolites in MCF-7 human breast cancer cells and an estrogen receptor
      competitive binding assay have been studied, respectively. The incubation of
      hepatocytes with HMB caused a concentration- and time-dependent decrease in cell
      viability, accompanied by loss of intracellular ATP and adenine nucleotide pools.
      HMB at a low-toxic level (0.25 mM) in the hepatocyte suspensions was converted
      enzymatically to 2,4-dihydroxybenzophenone (DHB) and a hydroxylated intermediate,
      which was tentatively identified as an isomer of 2,2prime prime or minute
      dihydroxy-4-methoxybenzophenone (DHMB) as determined by mass spectroscopy coupled
      with HPLC. Furthermore, the parent compound and both intermediates were rapidly
      conjugated to glucuronides, whereas free unconjugated DHMB and 2,3,4
      trihydroxybenzophenone (THB) were identified as trace intermediates. In another
      experiment, DHB and THB displaced competitively 17beta-estradiol bound to the
      recombinant human estrogen receptor alpha in a concentration-dependent manner:
      IC(50) of diethylstilbestrol and bisphenol A, which are known xenoestorogenic
      compounds, and DHB and THB was approximately 1 x 10(-8), 1 x 10(-5), 5 x 10(-5)
      and 5 x 10(-4) M, respectively. Further, DHB at concentrations from 10(-8) to 10(
      6) M caused a concentration-dependent proliferation of MCF-7 cells. DHMB and THB
      at 10(-7) and 10(-6) M also elicited a slight increase in cell numbers, whereas
      HMB at concentrations from 10(-9) to 10(-4) M did not affect the cell
      proliferation. Based on the relative IC50 for the competitive binding and the
      proliferative effect on MCF-7 cells, it follows that in estrogenic potency,
      DHB>THB>DHMB. These results indicate that some hydroxylated intermediates such as
      DHB rather than the parent compound act as a xenoestrogen via biotransformation.

PMID- 11823003
TI  - Acceleration of Drosophila melanogaster acetylcholinesterase
      methanesulfonylation: peripheral ligand D-tubocurarine enhances the affinity for
      small methanesulfonylfluoride.
AB  - D-Tubocurarine, a reversible peripheral inhibitor of cholinesterases accelerates
      methanesulfonylation of Drosophila melanogaster wild type and W359L mutant. The
      kinetic evaluation of the process was performed in a step-by-step analysis. The
      second order overall sulfonylation rate constants, determined from classical
      residual activity measurements, were used in the subsequent analysis of progress
      curves. The latter were obtained by measuring the hydrolysis of acetylthiocholine
      in a complex reaction system of enzyme, substrate, irreversible and reversible
      inhibitor. The underlying kinetic mechanisms, from such a complex data, could
      only be untangled by targeted inspection and successive incorporation of reaction
      steps for which experimental evidence existed. The study showed that the
      peripheral ligand D-tubocurarine, by binding at the entrance into the active site
      of the two investigated enzymes (Golicnik et al., Biochemistry 40 (2001) 1214),
      enhances the affinity for small methanesulfonylfluoride, rather to speeding up
      the formation of a stable covalent enzyme-inhibitor complex. The specific
      arrangements at the rim of the active site of each individual enzyme dictate the
      actual events which can be detected by kinetic means.

PMID- 11823002
TI  - DNA adduction by polychlorinated biphenyls: adducts derived from hepatic
      microsomal activation and from synthetic metabolites.
AB  - Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants and
      complete carcinogens in rodents. Metabolism of lower chlorinated congeners with
      rat liver microsomes was investigated in earlier studies and DNA adduction was
      also reported. The current study was designed to compare DNA adducts formed after
      bioactivation of PCBs with rat, mouse and human hepatic microsomes, and to
      investigate the role of quinoid PCB metabolites in DNA adduct formation. Eight
      congeners ranging from mono- to hexachlorinated biphenyls were tested.
      Metabolites obtained through microsomal bioactivation as well as synthetic
      quinoid metabolites of 4-monochlorobiphenyl (4-CB) were incubated with calf
      thymus DNA (CT-DNA), and the resulting adducts were analyzed by the 32P-post
      labelling method. DNA adducts were formed with mono- di- and tri-chlorinated
      congeners, but not with higher chlorinated congeners. Similar adduct patterns
      were observed for 2-monochlorobiphenyl (2-CB) activated with hepatic microsomes
      from rat, mouse and human, while 4-CB, 3,4-dichlorobiphenyl (3,4-CB) and 3,4,5
      trichlorobiphenyl (3,4,5-CB) showed similar patterns for two out of the three
      microsomal systems tested. 4,4' -trichlorobiphenyl (4,4' -CB) showed different
      adduct patterns in all microsomal systems. Higher adduct levels were obtained
      with the rodent microsomes compared with human microsomes and were related to
      higher cytochrome P450 activity. When adducts derived from microsomal activation
      of 4-CB were compared by co-chromatography with those derived from the incubation
      of DNA with synthetic 2-(4' -chlorophenyl)-1,4-benzoquinone (4-BQ), one adduct co
      migrated in three different chromatography systems. This study demonstrates that
      rodents as well as human hepatic enzymes metabolize lower chlorinated biphenyl
      congeners to reactive intermediates that form DNA adducts in vitro and shows that
      the para-quinone metabolites of PCBs are, in part, involved in direct DNA
      adduction.

PMID- 11823004
TI  - Expression of CD16, CD18 and CD56 in tributyltin-exposed human natural killer
      cells.
AB  - Tributyltin (TBT) was produced in large quantities for use in wood preservation,
      marine antifouling paints, disinfection of circulating industrial cooling waters
      and slime control in paper mills. TBT is found in dairy products, meat and fish.
      We and others have shown that there are measurable levels of TBT in human blood.
      BTs appear to increase the risk of cancer and viral infections in exposed
      individuals. In previous studies, we demonstrated that the NK-cytotoxic function
      of lymphocytes was greatly diminished after a 1-h exposure to 300 nM TBT or a 24
      h exposure to 200 nM TBT. Inhibition induced by a 1-h exposure to 300 nM TBT
      continues even after removal of the compound. There is also decreased ability of
      NK cells to bind to tumor target cells when they have been exposed to 200 nM TBT
      for 24 h. This loss of binding function is not seen when NK cells are exposed to
      300 nM TBT for 1 h. However, NK cells exposed to 300 nM TBT for 1 h and then
      incubated in TBT-free media for 24, 48 or 96 h, show a significant loss of tumor
      binding function by 96 h. The effects of TBT on cell surface molecules that are
      crucial to NK cell function is investigated. The data indicate there is a loss of
      expression of CD16 and CD56 on NK cells exposed to 200 nM TBT for 24 h. There is
      no decrease in expression of any of the markers studied when NK cells are exposed
      to 300 nM TBT for 1 h, consistent with the fact that a 1-h exposure has no effect
      on the ability of NK cells to bind to tumor targets. However, when NK cells are
      exposed to 300 nM TBT followed by 24, 48 or 96 h incubations in TBT-free media,
      there is a significant loss of CD16 and CD18 expression after 24 h and of CD16
      and CD56 expression after 48 and 96 h.

PMID- 11823005
TI  - Toxic effects of mercury(II), cadmium(II) and lead(II) porphyrins on Trypanosoma
      brucei brucei growth.
AB  - The effects of free mercury(II), cadmium(II) and lead(II) ions and their
      metalloporphyrin-derivatives on Trypanosoma brucei brucei growth in culture were
      studied. All experiments were conducted in the dark. IC(50) values on growth
      obtained in 24-h time-course experiments were 1.5 x 10(-7), 2.4 x 10(-6), 4.4 x
      10(-6) and 2.6 x 10(-5) M for mercury(II) porphyrin, cadmium(II) porphyrin,
      lead(II) porphyrin and free base porphyrin, respectively. While the IC50 values
      for Hg2+, Cd2+ and Pb2+ were 3.6 x 10(-6), 1.5 x 10(-5) and 1.6 x 10(-5) M,
      respectively. These results clearly indicate that the toxicity of the
      metalloporphyrin complexes of mercury(II), cadmium(II) and lead(II) to T. b.
      brucei parasites was much higher compared to their free metal ions and free base
      porphyrin at low concentrations. It was also observed after 8 h incubation that
      the metalloporphyrins were effective in inhibiting the division of the parasites
      at concentrations >1.25 x 10(-7) M for mercury(II) porphyrin, concentrations >1.2
      x 10(-6) M for cadmium(II) and lead(II) porphyrins and at concentrations >3.6 x
      10(-6) M for Hg2+ ion. These observations were not detected in samples treated
      with the free metal ions and the free base porphyrin at the same concentrations.
      Interestingly, trypanosomes treated with metalloporphyrin complexes displayed
      different morphological features from those cells treated with free base
      porphyrin or metal ions. The chemotherapeutic potential of the metalloporphyrins
      of H2TMPyP for treatment of African trypanosomiasis is discussed.

PMID- 11823006
TI  - Formation of 8-nitroguanosine in cellular RNA as a biomarker of exposure to
      reactive nitrogen species.
AB  - Reactive nitrogen species, such as peroxynitrite, nitrogen oxides and nitryl
      chloride, have been implicated as a cause of diverse pathophysiological
      conditions, including inflammation, neurodegenerative and cardiovascular diseases
      and cancer. We previously reported that 8-nitroguanine is formed by reactions of
      guanine or calf-thymus DNA with peroxynitrite in vitro. In the present study, we
      have studied the formation of 8-nitroguanosine and 8-oxo-7,8-dihydroguanosine in
      reactions of calf-liver RNA with various reactive nitrogen species. 8
      Nitroguanosine in RNA was found to be much more stable than 8-nitro-2' 
      deoxyguanosine in DNA, which rapidly depurinates to release 8-nitroguanine. Both
      8-nitroguanosine and 8-oxo-7,8-dihydroguanosine were formed in calf-liver RNA
      following exposure to various reactive nitrogen species, such as synthetic
      peroxynitrite. They were also formed in RNA by reactive species formed from
      nitric oxide and superoxide anion generated concomitantly from 3-morpholino
      sydnonimine (SIN-1) and those formed with myeloperoxidase or horseradish
      peroxidase in the presence of nitrite and hydrogen peroxide. 8-Nitroguanosine was
      detected by HPLC with an electrochemical detector in enzymatic hydrolyzates of
      RNA isolated from human lung carcinoma cells incubated with synthetic
      peroxynitrite. Our results indicate that 8-nitroguanosine in cellular RNA could
      be measured as a marker of damage caused by endogenous reactive nitrogen species
      in tissues and cells.

PMID- 11823007
TI  - Identification of new DNA adducts in human bladder epithelia exposed to the
      proximate metabolite of 4-aminobiphenyl using 32P-postlabeling method.
AB  - The DNA adducts were analyzed by 32P-postlabeling method following exposure of
      human uroepithelial cells (HUC) to N-hydroxy-4-aminobiphenyl (N-OH-ABP), the
      proximate metabolite of the human bladder carcinogen 4-aminobiphenyl (ABP). TLC
      of the postlabeled products on the first dimension revealed several products, the
      majority of which stayed close to the origin and were earlier identified as the
      3',5' -bisphospho derivatives of N-(deoxyguanosin-8-yl)-4-aminobiphenyl and N
      (deoxyadenosin-8-yl)-4-aminobiphenyl (Carcinogenesis 13 (1993) 955;
      Carcinogenesis 16 (1995) 295). Here we report characterization of two additional
      adducts that amounted to less than 5% of the total adducts. Autoradiography of D1
      chromatogram of the postlabeled products of calf thymus DNA chemically interacted
      with N-OH-ABP under acidic conditions revealed two adducts, #1 and #2, with R(f)
      values of about 0.2 and 0.3, respectively. Two adducts with D1 thin layer
      chromatographic properties similar to those of adducts #1 and #2 were obtained on
      postlabeling analyses of products generated by chemical interaction of N-acetoxy
      4-aminobiphenyl (N-OAc-ABP) with deoxyguanosine-3' -monophosphate (dGp). Based on
      proton NMR and mass spectroscopic analyses of the synthetic products derived from
      N-OAc-ABP, the chemical structures of adducts #1 and #2 have been identified as 3
      (deoxyguanosin-N(2)-yl)-4-aminobiphenyl, and N-(deoxyguanosin-N(2)-yl)-4
      aminobiphenyl, respectively. Both of these adducts were insensitive to digestion
      with nuclease P1. 32P-Postlabeling analysis of the nuclease P1 enriched DNA
      hydrolysate of HUC cells treated with N-OH-ABP showed the presence of adduct #2
      but not adduct #1. Adduct #2 was also detected in calf thymus DNA incubated with
      HUC cytosol and N-OH-ABP in the presence of acetyl CoA. These results suggest
      that in the target cells for ABP carcinogenesis in vivo, N-OH-ABP is bioactivated
      by acetyl CoA-dependent acyltransferases to reactive arylnitrenium ions that
      covalently interact at N(2)-position of deoxyguanosine in DNA.

PMID- 11823008
TI  - Involvement of protein tyrosine phosphorylation and reduction of cellular
      sulfhydryl groups in cell death induced by 1' -acetoxychavicol acetate in Ehrlich
      ascites tumor cells.
AB  - Elucidation of the mechanisms underlying potential anticancer drugs continues and
      unraveling these mechanisms would not only provide a conceptual framework for
      drug design but also promote use of natural products for chemotherapy. To further
      evaluate the efficacy of the anticancer activity of 1'-acetoxychavicol acetate
      (ACA), this study investigates the underlying mechanisms by which ACA induces
      death of Ehrlich ascites tumor cells. ACA treatment induced loss of cell
      viability, and Western blotting analysis revealed that the compound stimulated
      tyrosine phosphorylation of several proteins with 27 and 70 kDa proteins being
      regulated in both dose- and time-dependent manner prior to loss of viability.
      Protein tyrosine kinase inhibitor herbimycin A moderately protected cells from
      ACA-induced toxicity. In addition, cellular glutathione and protein sulfydryl
      groups were also significantly reduced both dose- and time-dependently during
      evidence of cell death. Replenishing thiol levels by antioxidant, N
      acetylcysteine (NAC), an excellent supplier of glutathione and precursor of
      glutathione, substantially recovered the viability loss, but the recovery being
      time-dependent, as late addition of NAC (at least 30 min after ACA addition to
      cultures) was, however, ineffective. Addition of NAC to ACA treated cultures also
      abolished tyrosine phosphorylation of the 27 kDa protein. These results, at least
      partly, identify cellular sulfhydryl groups and protein tyrosine phosphorylation
      as targets of ACA cytotoxicity in tumor cells.

PMID- 11823009
TI  - The effect of thermocycling regimens on the nanoleakage of dentin bonding
      systems.
AB  - OBJECTIVES: The purpose of this study was to compare nanoleakage associated with
      polished and fractured specimens, and evaluate the effects of thermocycling on
      nanoleakage. METHODS: The dentin bonding systems used in this study were
      PermaQuik and Prime and Bond NT (PBNT). Flat occlusal dentin surfaces and class V
      cavities from extracted human molars were bonded with one of the dentin bonding
      systems. With or without thermocycling, samples were immersed in a 50% w/v
      solution of silver nitrate for 24h, and exposed to photodeveloping solution for
      8h. The specimens were cut or fractured, and mounted on stubs, carbon coated and
      observed in a Field Emission-SEM using backscattered electron mode. RESULTS:
      Polished and fractured specimens showed similar nanoleakage patterns for both
      dentin-bonding systems. Thermocycling with regimens of different temperatures and
      number of cycles did not result in different nanoleakage patterns and leakage
      lengths in controls and thermocycled groups. PBNT combined with non-rinse
      conditioner (NRC) produced no significant difference in nanoleakage length, but a
      somewhat different nanoleakage pattern, compared with PBNT and 34% phosphoric
      acid. SIGNIFICANCE: Thermocycling does not have an effect on nanoleakage of
      dentin bonding systems. The smearing effect from sectioning and polishing
      procedures does not affect the nanoleakage result.

PMID- 11823011
TI  - Marginal gap formation of light-activated restorative materials: effects of
      immediate setting shrinkage and bond strength.
AB  - OBJECTIVES: The purpose of this study was to explore multiple correlations
      between shrinkage, bonding and marginal gap parameters, immediately after light
      activation, for three classes of restorative materials. The correlations of
      interest were between: (a) their marginal gap formation in tooth cavities, (b)
      their free setting shrinkage-strain determined by two different measurement
      methods ((i) the marginal gap-width in a non-bonding Teflon cavity and (ii) a
      linear (diametral) measure of shrinkage-strain), and (c) their shear bond
      strengths to enamel and to dentin. METHODS: The maximum marginal gap width and
      the opposing width (if any) in the tooth cavity were measured immediately (3 min)
      after light-activation. Two factors for the setting shrinkage-strain and the
      shear bond strength to enamel and to dentin were measured concomitantly. RESULTS:
      Out of the set of restorative materials investigated, those that produced a
      smaller marginal gap in the tooth cavity had a smaller marginal gap in the Teflon
      cavity. There was a highly significant correlation between the two parameters
      (r=0.914, p<0.001). However, no relationship was observed between the marginal
      gap in the tooth cavity and the immediate diametral shrinkage-strain (p>0.05).
      Thus the restorative materials that produced a smaller marginal gap in the tooth
      cavity did not generally have a smaller diametral setting shrinkage-strain.
      Furthermore, no relationship was observed between the marginal gap in the tooth
      cavity and the shear bond strength to enamel or to dentin (p>0.50). SIGNIFICANCE:
      For light-activated restorative materials during the early stage of setting (<5
      min), the free shrinkage-strain, measured by marginal-gaps in Teflon cavities,
      had a greater correlation with immediate marginal-gaps in tooth cavities than
      either the immediate diametral shrinkage-strain or the bond strengths to the
      tooth structure.

PMID- 11823010
TI  - Dynamic mechanical analysis of storage modulus development in light-activated
      polymer matrix composites.
AB  - OBJECTIVES: The goal of this study was to evaluate the potential for using
      dynamic mechanical analysis of tubular geometry in a three-point flexure fixture
      for monitoring the storage modulus development of a light-activated polymer
      matrix composite. METHODS: Composite samples were inserted into PTFE tubes and
      tested in a three-point bend fixture in a dynamic mechanical analyzer (DMA) at
      200 Hz with 20 microm amplitude. Samples were light activated for 60s (385
      mW/cm(2) at the composite surface) and storage modulus (E') was measured
      continuously for the seven light-activated composites studied (one microfill,
      four hybrids and two unfilled resins). Cores of composite were removed from the
      PTFE sheath after 13.5 min and evaluated with the same parameters in the DMA. A
      finite element model of the test configuration was created and used to estimate
      operating parameters for the DMA. Degree of conversion (DC) was measured using
      micro-Fourier Transform Infrared (FTIR) spectroscopy for the microfilled
      composite samples and one hybrid 13.5 and 60 min after light activation. RESULTS:
      The E' for a generic hybrid and microfilled composite was 13,400+/-1100 and
      5900+/-200 MPa, respectively, when cured within the tube and then removed and
      tested in the DMA. DC was 54.6% for the hybrid and 60.6% for the microfill. A
      linear regression of E' for the sheath and core vs core alone (r(2)=0.986)
      indicated a linear scaling of the sheath and core values for E' enabling a
      correction for estimated E' values of the composite core. SIGNIFICANCE: This
      method estimates the storage modulus growth during light-activated polymerization
      of highly filled dimethacrylates. Although the approach is phenomenological in
      that quantitative measurements of E' are not made directly from the DMA,
      estimates of early polymerization kinetics appear to be validated by three
      different approaches.

PMID- 11823012
TI  - Instrumented indentation characterisation of mouth-guard materials.
AB  - OBJECTIVES: The aim of the study was to investigate the mechanical properties and
      energy absorption behavior of mouth-guard materials. Interpretation of
      indentation force-displacement data has been used to determine these properties.
      METHODS: An ultra micro-indentation system (UMIS) was used to determine near
      surface properties of mouth-guard materials with nanometer and micro-Newton
      displacement and force resolution. The measurement procedure was conducted with a
      small spherical steel indenter (R=500 microm), with impressions that were equally
      spaced (250 microm). Measurements of force-displacement response of surfaces at
      maximum forces of 10, 40 or 50 mN, 10 indentations were made at each of these
      forces. Tests were undertaken in two different modes to determine the mechanical
      properties, namely: (a) continuous load to the maximum force and then unload, (b)
      multiple loading and partially unloading sequence to the maximum load. RESULTS:
      The force-displacement results were analysed to determine the elastic modulus and
      contact pressure versus depth of penetration as well as the energy loss. Energy
      absorption for each material was determined from the ratio of the hysteresis
      energy loss to the total energy at maximum load and ranged from 10 to 24% among
      different mouth-guard materials. Energy absorption ratio, elastic modulus and
      contact pressure were significantly different between different materials with
      same thickness (FC, GC and C3) (p<0.01) and significantly different between
      materials with different thickness (C1 and C3) (p<0.01). SIGNIFICANCE: The
      present approach provides a simple and efficient method to readily measure the
      elastic-plastic (hysteretic) response of mouth-guard materials. The indentation
      technique lends itself to investigate the influence of ageing, heat treatment,
      sterilisation, moisture etc in a simple systematic manner.

PMID- 11823013
TI  - Strength and fracture toughness of MgO-modified glass infiltrated alumina for
      CAD/CAM.
AB  - OBJECTIVE: This study was conducted to investigate the effect of MgO additive to
      Al2O3 on the flexural strength, fracture toughness of glass infiltrated alumina
      for CAD/CAM application. METHODS: Alumina blanks with additive of 0.5 wt% MgO
      were prepared via isostatic pressing and sintering at 1400 degrees C for 2h, and
      then alumina-glass composites were fabricated by infiltrating the molten glass
      into the partially sintered alumina compact. Flexural strength and fracture
      toughness were determined using three point bending methods and a single edge
      notched beam method. The mechanism of crack propagation was observed under a
      field emission scanning electron microscope. RESULTS: The three-point flexural
      strength and fracture toughness of partially sintered alumina and alumina-glass
      composite were 210 MPa, 1.86 MPam(1/2), and 432.2 MPa, 5.12 MPam(1/2),
      respectively, and they were free of shrinkage during the processing of glass
      infiltration. The field emission SEM micrograph indicated that indentation caused
      a non-planar crack propagation including crack deflection and crack bowing.
      SIGNIFICANCE: MgO was used as an additive to alumina to improve the strength and
      fracture toughness of partially sintered alumina and alumina-glass composite. The
      high strength and toughness are related to toughening by the distribution of
      alumina with uniform particle sizes, crack bowing, crack deflection and the
      beneficial wetting properties of the particle surface.

PMID- 11823014
TI  - The effect of irradiation wavelength bandwidth and spot size on the scraping
      depth and temperature rise in composite exposed to an argon laser or a
      conventional quartz-tungsten-halogen source.
AB  - OBJECTIVES: The purpose of this study was to investigate the effect of the
      spectral distribution of the curing irradiation near the maximum excitation
      wavelength of the photo-initiator and the effect of the irradiation spot size on
      the scraping depth-of-cure and temperature rise in a resin composite for both an
      argon laser and a quartz-tungsten-halogen lamp. METHODS: Using bandpass filters,
      the spectral outputs of an argon laser and a quartz-tungsten-halogen lamp were
      restricted to pass selected wavelengths on to a commercial camphorquinone-based
      resin composite and the depth-of-cure, using scraping methods, was measured. The
      temperature rise in composite was measured for some of the above-mentioned
      sources. The spot sizes for both sources were varied and the scraping depth was
      measured. Lateral curing or the extent of curing away from the focused spot was
      also measured. RESULTS: For constant power density and exposure time, an
      irradiation spectral distribution closer to the photo-initiator excitation peak
      yielded a higher scraping depth than a broadband spectral distribution for both
      sources. Under similar conditions, the argon laser resulted in a lower
      temperature rise in the composite than the lamp. For the same total energy
      imparted to the resin composite, the scraping depth increased with reducing spot
      size of the curing irradiation. Furthermore lateral curing of the composite well
      beyond the irradiation spot size was observed. SIGNIFICANCE: The spectral and
      spatial characteristics of the curing irradiation need to be carefully considered
      as these affect the scraping depth-of-cure and temperature rise in a resin
      composite.

PMID- 11823015
TI  - The use of flowable composites as filled adhesives.
AB  - OBJECTIVE: The effect of filled adhesives on bonding resin composites to dentin
      has not been fully understood. Due to their filler content, filled adhesives may
      act as stress breakers. The aim of this in vitro study was to evaluate the use of
      flowable composites of different viscosities on bonding to enamel and dentin
      without the use of an intermediate bonding resin. MATERIALS AND METHODS: Enamel
      and dentin bond strengths of OptiBond FL, Syntac Classic, and EBS Multi combined
      either with their proprietary bonding agent or a flowable resin composite
      (Ultraseal XT Plus or Revolution) were measured. The tests were carried out with
      a microtensile device at a crosshead speed of 1mm/min after 24h of storage at 37
      degrees C in water. Mean bond strengths were analyzed using the Wilcoxon test and
      multiple comparisons according to the Mann-Whitney U-test. The micro-morphology
      of corresponding resin-dentin interfaces of the same teeth were analyzed using
      SEM and TEM. RESULTS: The control groups with adhesive systems used as per
      manufacturers' protocol showed bond strengths of 38.9-41.1 MPa to enamel and 28.8
      33.4 MPa to dentin. With respect to bond strength to etched enamel, only
      Ultraseal XT Plus as bonding resin reached the level of the control groups. When
      used as bonding agents on dentin, both flowable composites produced lower
      microtensile bond strengths to etched and primed dentin than did the control
      groups. Micro-morphological analysis using SEM and TEM resulted in hybrid layer
      formation for both control and experimental groups. However, many areas of the
      resin-dentin interface showed insufficient penetration of the flowable composites
      at the top of the hybrid layer as well as numerous tubules obstructed by filler
      particles. CONCLUSIONS: The flowable composites tested in this study should not
      be used to replace bonding agents. Flowable composites of thinner viscosity, such
      as Ultraseal XT Plus, may bond to enamel adequately without the requirement of an
      intermediate bonding resin.

PMID- 11823016
TI  - A comparison of microtensile bond strengths of several dentin bonding systems to
      primary and permanent dentin.
AB  - OBJECTIVES: Limited information exists with regard to the adhesive ability of
      glass ionomer cements (GIC) and recently developed resin-based dentin bond
      systems to primary dentin. The aim of this study was to compare the microtensile
      bond strength of a conventional GIC (Fuji IX), a resin-modified GIC (Fuji II LC),
      and two resin-based dentin adhesives (Prime and Bond NT with NRC and Single
      Bond). The bonded interfaces were also observed using field emission electron
      microscopy(FE-SEM). METHODS: Microtensile bond test specimens were prepared on
      superficial dentin of primary and permanent molars. The specimens were bonded
      according to each manufacturer's instructions except for Prime and Bond NT/NRC
      which used Silux Plus resin composite instead of Dyract. Hour-glass shaped
      specimens were created (diameter of 1.2+/-0.02 mm) and stressed in tension at a
      crosshead speed of 1mm/min. Results were analyzed using two-way ANOVA and LSD
      test, fracture modes were analyzed using the Mann-Whitney U-test and Kruskall
      Wallis test. Twelve specimens were prepared for each material on primary and
      permanent dentin. Samples were prepared in the same manner, then critical point
      dried, fractured and sputter-coated for the FE-SEM observations. RESULTS: Two-way
      ANOVA showed the overall bond strengths were greater for the permanent dentin
      compared with primary dentin. However, for individual material comparisons no
      differences among the bond strengths to primary and permanent dentin for Fuji IX
      (9.7, 12.2 MPa), Fuji II LC (16, 20.1 MPa), Prime & Bond NT/NRC (18.1, 21.6 MPa)
      and Single Bond (18.2, 21.6 MPa), were detected. However, Fuji IX bond strengths
      were significantly lower than the other systems tested when bonded to either
      primary or permanent dentin (p<0.05). Failure mode showed cohesive failure of GIC
      and mostly adhesive failure for the resin-based adhesives. The FE-SEM
      observations showed hybrid-like layer formation for the GIC materials and hybrid
      layer formation for the resin-based adhesives. SIGNIFICANCE: The materials tested
      would be suitable for bonding to either primary or permanent dentin, but the
      resin-modified GIC or resin-based systems are likely to provide a stronger bond
      than the conventional GIC, Fuji IX.

PMID- 11823017
TI  - Potential countersample materials for in vitro simulation wear testing.
AB  - OBJECTIVES: Any laboratory investigation of the wear resistance of dental
      materials needs to consider oral conditions so that in vitro wear results can be
      correlated with in vivo findings. The choice of the countersample is a critical
      factor in establishing the pattern of tribological wear and in achieving an
      efficient in vitro wear testing system. This research investigated the wear
      behavior and surface characteristics associated with three candidate
      countersample materials used for in vitro wear testing in order to identify a
      possible suitable substitute for human dental enamel. METHODS: Three candidate
      materials, stainless steel, steatite and dental porcelain were evaluated and
      compared to human enamel. A variety of factors including hardness, wear surface
      evolution and frictional coefficients were considered, relative to the tribology
      of the in vivo situation. RESULTS: The results suggested that the dental
      porcelain investigated bore the closest similarity to human enamel of the
      materials investigated. SIGNIFICANCE: Assessment of potential countersample
      materials should be based on the essential tribological simulation supported by
      investigations of mechanical, chemical and structural properties. The selected
      dental porcelain had the best simulating ability among the three selected
      countersample materials and this class of material may be considered as a
      possible countersample material for in vitro wear test purposes. Further studies
      are required, employing a wider range of dental ceramics, in order to optimise
      the choice of countersample material for standardized in vitro wear testing.

PMID- 11823018
TI  - Sensitivity of a disc rupture strength test to air bubble pores in phosphate
      bonded investment materials at elevated temperatures.
AB  - OBJECTIVES: To investigate the sensitivity of a modified disc rupture test to
      variables affecting the strength of four phosphate-bonded investment materials
      under conditions closely resembling the in-service environment. This study
      examined the influence of air bubble pores on the strength of phosphate bonded
      investment materials at a temperature of 900 degrees C. METHODS: A modified disc
      rupture configuration was used to test a circular investment diaphragm with
      clamped edges, in tension, initiated by bending. A sequentially-varying molten
      metal mass was used to apply the load using an electronic centrifugal casting
      machine. The staircase method was used to determine the increase or decrease of
      the applied load with the standardized increment of load being no greater than 1
      or 2g. The mean load applied to 30 samples defined the transition of survival to
      failure of the investment disc and was taken as a measurement of investment
      strength. Two material handling techniques, one giving virtually no pores and one
      showing a wide pore size distribution were used. RESULTS: The diaphragm clearly
      either failed or survived the test with the pattern of fracture indicating
      brittle failure. A statistically significant difference in strength (P<0.050) of
      diaphragms with and without air bubble pores was demonstrated for three
      materials. Fewer pores resulted in increased strength of those materials and
      produced a much reduced scatter of strength in the fourth. SIGNIFICANCE: The
      modified disc rupture test is sufficiently sensitive to identify variations in
      strength of phosphate bonded investment materials caused by differing pore size
      distributions.

PMID- 11823019
TI  - Effects of mechanical properties of adhesive resins on bond strength to dentin.
AB  - OBJECTIVES: The purpose of this study was to evaluate the relationship between
      the micro-tensile bond strength to dentin and mechanical properties of the cured
      adhesive resins. METHODS: Coronal dentin surfaces of extracted human teeth were
      treated with four commercial self-etching priming systems (Clearfil SE Bond;
      UniFil Bond; Tokuso Mac-Bond II; and Imperva Fluoro Bond) and bonded with a resin
      composite. After 24h storage in water at 37 degrees C, the bonded specimens were
      trimmed and subjected to micro-tensile bond strength testing at a cross-head
      speed of 1mm/min. Debonded surfaces were observed under a FE-SEM. For testing
      mechanical properties, 0.7-mm thick slabs of each adhesive resin were prepared,
      light-cured, and stored dry at the room temperature for 24h. After trimming,
      ultimate micro-tensile strength was measured. The nano-hardness and Young's
      modulus were also evaluated using cured adhesives that were prepared in the same
      manner as described above. RESULTS: The micro-tensile bond strengths to dentin
      and ultimate micro-tensile strengths of the resins were not significantly
      different among all systems (P>0.05). However, the nano-hardness and Young's
      modulus of Clearfil SE Bond and Imperva Fluoro Bond adhesive resins were
      significantly higher than those of UniFil Bond and Tokuso Mac-Bond II resins
      (P<0.05). The micro-tensile bond strength significantly correlated with the
      ultimate micro-tensile strength of the resins (r(2)=0.77; P<0.05), but was not
      correlated with the nano-hardness or Young's modulus (P>0.05). SEM observation of
      the debonded surfaces revealed a mixed type of fracture with a combination of
      interfacial and cohesive failure within the adhesive resin. SIGNIFICANCE: The
      four self-etching priming systems exhibited similar dentin bond strengths, which
      also correlates with the ultimate strength of the adhesive resins.

PMID- 11823021
TI  - Long-term tensile bond durability of two different 4-META containing resin
      cements to dentin.
AB  - OBJECTIVES: This study was conducted to evaluate the tensile bond durability of
      two different types of 4-META containing resin cements over a period of 3 years.
      METHODS: Ten bovine dentin specimens were tested for tensile bond strengths with
      each of the following materials: Super Bond C&B: unfilled methyl methacrylate
      (MMA)/polymethyl methacrylate (PMMA) resin cement, MASA Bond (experimental
      material): filled dimethacrylate resin cement at 1 day, 6 months, 1 and 3 years.
      The mean bond strengths were compared statistically by two-way ANOVA and Fisher's
      PLSD test (P<0.05). The mode of failure was classified by SEM observation.
      Results for the mode of fracture were analyzed using the Mann-Whitney U test.
      RESULTS: Although there was no statistical difference in mean bond strength
      between Super Bond C&B and MASA Bond (P>0.05) during the experimental periods,
      the 1-day bond strengths were significantly greater than those at the other
      experimental periods except for 6 months (P<0.05). Regarding the fracture modes,
      at 6 months and 1 year, statistical differences were observed between Super Bond
      C&B and MASA Bond (P<0.05). SIGNIFICANCE: The bond strengths of both resin
      cements to dentin significantly decreased after 6 months, and the long-term
      failure patterns of the 4-META/TBB resin cements showed a marked change.

PMID- 11823020
TI  - Evaluation of thermal cycling and mechanical loading on bond strength of a self
      etching primer system to dentin.
AB  - OBJECTIVE: The aim of this study was to evaluate the in vitro durability and
      fracture modes of the tooth-resin interface following thermal cycling, fatigue
      load cycling (FLC) and micro-tensile bond strength testing (MTBS). METHODS:
      Twenty-four human molars were divided into two groups. In group A, coronal dentin
      was ground flat with #600-grit SiC paper, Clearfil Linerbond.2V (LB.2V) adhesive
      was applied and a crown fabricated with Clearfil AP-X resin composite. Samples
      were loaded in the FLC simulator and thermal cycle device. In group B, Class I
      cavities were prepared with a diamond bur and the cavity restored with LB.2V/AP
      X. Samples were simultaneously subjected to FLC and thermal cycling. After
      storage of the specimens in water for 1 week, MTBS tests were performed, and
      fracture modes examined by SEM. RESULTS: For group A, MTBS were approximately 40
      MPa with cohesive failures in the bonding resin of all specimens. Neither thermal
      nor mechanical stressing altered bond strengths on flat dentin surfaces. In group
      B, MTBS in the unstressed control group was 21 MPa with cohesive failures in the
      resin. As both thermal and mechanical stresses increased, there was a significant
      decrease in bond strength (16 MPa, P<0.05) and the fractures were seen in the
      resin-dentin interface and hybrid layer. SIGNIFICANCE: Surface preparation, C
      factor, cavity depth, the dentin substrate and character of the smear layer
      strongly influence the bond strength values after thermal and fatigue loading.
      The FLC simulator in combination with MTBS testing provides meaningful in vitro
      evaluation of dentin bonding durability.

PMID- 11823022
TI  - New organosilicon maxillofacial prosthetic materials.
AB  - OBJECTIVES: The silicone elastomer A-2186 is a widely used maxillofacial
      prosthetic material. It is a pourable two-component silicone rubber cured by a
      platinum catalyst. Used as a prosthetic material, A-2186 has short working time
      and because of its hydrophobic nature, poor adhesion to non-silicone based
      adhesives. The purpose of this study is to evaluate the physical properties of
      new prosthetic materials based on methacryloxypropyl-terminated
      polydimethylsiloxane (MPDS-MF), and to compare the properties with those of A
      2186. METHODS: Hardness, tensile strength, ultimate elongation, tear strength and
      adhesive bonding strength of MPDS-MF and A-2186 with and without additives were
      determined and compared. The bonding strengths of the extrinsic colorant carrier
      with the prosthetic materials were also determined. Statistical analyses were
      done using a two-way analysis of variance (ANOVA). For significant effects, post
      hoc tests were done using the Bonferroni correction. RESULTS: The hardness of
      MPDS-MF is similar to A-2186. However, tensile strength, tear strength, ultimate
      elongation, and adhesive bonding strength of MPDS-MF are higher than those of A
      2186. SIGNIFICANCE: MPDS-MF is cured by free radical thermal polymerization and
      crosslinking. The working time of MPDS-MF, unlike A-2186, is long. The presence
      of methacrylate groups in MPDS-MF enhances its adhesion to non-silicone based
      adhesive. Based on the present study, it appears that MPDS-MF is suitable for use
      in fabricating of clinical prostheses.

PMID- 11823023
TI  - Measures of goal attainment and performance in the World Health Report 2000: a
      brief, critical consumer guide.
AB  - The World Health Report 2000 presents a set of indicators and global indices by
      which different countries' goal attainment and performance in health care may be
      compared. The paper explains the methods employed in some detail and raises a
      number of critical points. The WHO has gone too far in compressing the results of
      potentially useful primary measurements in summary indices with unclear meaning,
      dubious validity and little practical relevance to decision makers facing
      specific tasks and problems. The WHO has also gone too far in applying the same
      measuring rods to countries with different histories and values and different
      stages of development, and in encouraging international comparisons that are of
      little use to policy makers. The WHO needs to add an indicator of equality in
      access to its present indicator of fairness in financing.

PMID- 11823024
TI  - A 'transitional' context for health policy development: the Palestinian case.
AB  - The objective of this article is to focus on the challenges and opportunities the
      Palestinian health care system is currently facing in a 'transitional period',
      which started subsequent to the Oslo Agreement in 1993. The characteristics of
      'transition' have to be highlighted in order to understand the context and
      peculiarities in which the Palestinian health care system is operating. A
      descriptive analysis is provided of the historical, political, economic and socio
      demographic elements to gain an insight into the complex context of the Occupied
      Palestinian Territories, a country in 'transition'.

PMID- 11823025
TI  - Health target programmes and health care services--any link?: a conceptual and
      comparative study (part 1).
AB  - Against the background of the separation between health policy being concerned
      mainly with cost-containment on the one hand and the commitment to 'Health for
      all' based on health target programmes on the other, we undertook a conceptual
      and comparative study of the policy documents of national and regional health
      target programmes in countries of the European Union, Australia, Canada, New
      Zealand and the USA to analyse (1) whether they define objectives for health
      care; and (2) whether they have a clear orientation towards health outcomes. With
      the exception of Australia, health target programmes focus on intervention areas
      outside health services which explains why they remain in the 'forgotten corner'
      of health policy. Therefore, there is a need to develop an integrated approach,
      combining health targets for all possible intervention areas including health
      services, to fully utilise the potential of health target programmes.

PMID- 11823026
TI  - Outcome-related health targets--political strategies for better health outcomes:
      a conceptual and comparative study (part 2).
AB  - Based on an analytical model which defines political co-ordinates on two axes
      (technocratic-participative and top-bottom), the policy documents of national and
      regional health target programmes in countries of the European Union, Australia,
      Canada, New Zealand and the USA are analysed in regard to the rationale for and
      interest in health targets, the involvement of actors in the policy-cycle, the
      setting of priorities, the distribution of responsibilities and accountability as
      well as incentives and sanctions used. Most, if not all, target programmes are
      conceptualised in a 'top-down' manner by the government and its administration
      with little involvement of the general public or the parliament. Usually, neither
      necessary alliances at the grass roots level nor appropriate incentives for local
      or professional actors are discussed in the documents. Many target programmes
      are, therefore, bound to fail and finding a balance between the right balance
      between technocratic and participative as well as between top and bottom remains
      a challenge for setting successful health targets.

PMID- 11823027
TI  - Analysis of hospital charges for cerebral infarction stroke inpatients in
      Beijing, People's Republic of China.
AB  - OBJECTIVE: Stroke is a heavy economic burden on the individuals, society and
      health services in China, where health expenditure is rising rapidly. The purpose
      of the present study is to examine health services and demographic factors
      associated with inpatient charges for cerebral infarction in China, focusing on
      hospital charges of insured and uninsured patients. METHODS: The study subjects
      were 545 patients with a principal diagnosis of cerebral infarction stroke who
      were discharged from the China-Japan Friendship Hospital from January 1, 1997
      through December 31, 1998. Demographic, clinical and administrative data were
      retrospectively collected from the medical record and financial database. The
      influence of social and medical factors on total charges was analyzed with
      stepwise multiple regression model. RESULTS: Of 545 subjects, 429 (79%) were the
      insured patients and 116 (21%) were the uninsured patients. Length of hospital
      stay (LOHS) for the insured patients (median, 32 days) was significantly longer
      (P<0.001) than that for the uninsured (median, 23 days). The hospital charges per
      discharge for the insured was significantly higher (geometric mean, 10407 yuan)
      (P<0.0001) than that for the uninsured patients (geometric mean, 5857 yuan). With
      stepwise multiple regression, factors associated independently with the hospital
      charge were: longer hospital stay, insurance status, increased number of head
      magnetic resonance imaging (MRI) and computerized tomography (CT), infection in
      hospital stay, and more severe condition of stroke. CONCLUSIONS: Inpatient charge
      for cerebral infarction stroke was positively associated with being the insured.
      The findings suggest an overuse of health care resources in insured patients and
      limited use of resources by those who are not.

PMID- 11823028
TI  - The use of contracts in the management of infectious disease related risk in the
      NHS internal market.
AB  - The paper reports a unique study of contracting for infectious disease control in
      the English National Health Service internal market. New-institutional economic
      and socio-legal theories are used to predict that it will not be possible to make
      contracts for the control of infectious disease which are complete with respect
      to either the allocation of financial risk or the specification of quality
      standards. Socio-legal theory predicts that in some circumstances informal
      relationships (known as networks or relational contracts) can evolve to
      compensate for some of the deficiencies of incomplete contracts. NHS policy
      makers are shown to have expected and continue to expect that contracts can be
      complete. The study comprised five in-depth case studies of contracting in
      different local areas in England and a national survey of all infection control
      professionals. The results confirm the theoretical predictions. Contracts were
      not complete, and some of the elements of relational contracts were present.
      These elements did not, however, fully compensate for the lack of clear
      accountability caused by contractual incompleteness.

PMID- 11823029
TI  - Metastatic squamous cell carcinoma with marked blood eosinophilia and elevated
      serum interleukin-5 levels.

PMID- 11823030
TI  - Changing phenotypes of hematopoietic stem cells.

PMID- 11823031
TI  - Hematopoietic stem cell transplantation after reduced-intensity conditioning as
      treatment of sickle cell disease.
AB  - OBJECTIVE: Sickle cell disease generates considerable morbidity and mortality.
      Allogeneic hematopoietic stem cell transplantation (SCT) has the potential of
      curing the disease and halting end-organ damage. However, in older patients this
      treatment is associated with a significant risk of toxicity and death. SCT after
      reduced-intensity conditioning (RIC) might be a safer approach for the treatment
      of sickle cell disease. MATERIALS AND METHODS: A 22-year-old male had experienced
      multiple, life-threatening hemolytic crises. We treated him with G-CSF-mobilized
      stem cells from his heterozygote, human leukocyte antigen-matched brother after
      RIC with fludarabine and cyclophosphamide. GVHD prophylaxis consisted of
      cyclosporine (CyA) and mycophenolate mofetil (MMF). Chimerism of peripheral blood
      mononuclear cells was evaluated using short tandem repeat analysis and hemoglobin
      analysis was performed by high-performance liquid chromatography. RESULTS: There
      were no major treatment-related toxicities. At day +30 after transplantation the
      patient had mixed hematopoietic chimerism, which later converted to full
      chimerism. Hemoglobin analysis revealed 3.4% HbA(2), 1.0% HbF, and 41.2% HbS,
      which essentially is the same hemoglobin partition as in his brother's blood. MMF
      was discontinued on day +35 and CyA on day +120. After discontinuation of CyA the
      patient developed mild chronic GVHD, which resolved with continued CyA, low-dose
      steroids, and the retinoid isotretinoin. He is doing well on day +315 without
      evidence of GVHD. CONCLUSIONS: Allogeneic SCT after RIC is feasible in adult
      patients with sickle cell disease. Mixed chimerism is sufficient to relieve
      disease-related symptoms and is possibly correlated with less acute GVHD.

PMID- 11823032
TI  - Lentiviral vector-mediated transduction of murine CD34(-) hematopoietic stem
      cells.
AB  - OBJECTIVE: Efficient gene transfer into murine hematopoietic stem cells (HSCs)
      provides a powerful tool for exploring hematopoietic stem cell biology. In this
      study, we evaluated the efficiency of lentiviral vector-mediated gene transfer
      into murine CD34(-/low)c-Kit(+)Sca-1(+)Lin(-) (CD34(-) KSL) cells that are highly
      enriched for HSCs. MATERIALS AND METHODS: FACS-sorted CD34(-) KSL cells were
      transduced with the vesicular stomatitis virus G glycoprotein-pseudotyped HIV-1
      based lentiviral vector containing the green fluorescent protein (GFP) gene under
      the control of the cytomegalovirus promoter, and then 50 transduced cells were
      transplanted into lethally irradiated mice. Transduction efficiency was assessed
      by FACS analysis for GFP expression in peripheral blood (PB) cells. FACS-sorted
      GFP(+) KSL bone marrow (BM) cells from primary recipients were used for secondary
      transplantation, and GFP expression in PB cells of reconstituted mice was
      analyzed by FACS. RESULTS: GFP expression was detected in PB cells of all primary
      recipients (n = 10) at an average of 40% (range 26-58%) when the lentiviral
      vector containing the woodchuck hepatitis virus posttranscriptional regulatory
      element was used. GFP(+) cells were found in multilineage cells in PB, BM,
      spleen, and thymus for at least 8 months posttransplantation. In secondary
      recipients, donor-derived GFP(+) KSL BM cells could reconstitute and GFP
      expression was detected in both myeloid and lymphoid cells in PB. CONCLUSION: Our
      results indicate that lentiviral vectors can efficiently transduce highly
      enriched murine HSCs and sustain long-term expression of the transgene in the
      multilineage differentiated progeny in reconstituted mice.

PMID- 11823033
TI  - Paroxysmal nocturnal hemoglobinuria: Differential gene expression of EGR-1 and
      TAXREB107.
AB  - OBJECTIVE: Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal defect
      of hematopoietic stem cells characterized by deficiency in GPI-anchored surface
      proteins. It is not yet known how GPI-deficient stem cells are able to expand
      within the bone marrow and contribute considerably to the hematopoiesis. In PNH,
      as well as in AA and MDS, genetic instability and increased mutation frequency
      have been detected. Therefore, a second event is very likely, such as additional
      mutations, leading to clonal expansion of GPI-deficient bone marrow stem cell in
      PNH. METHODS: In order to elucidate the molecular basis of clonal expansion in
      PNH, we identified several genes differentially expressed in normal and GPI
      deficient cells of PNH patients by combination of RNA fingerprinting and cDNA
      array hybridization. RESULTS: Expression of two of these genes, EGR-1 and
      TAXREB107, has been further investigated. EGR-1 is upregulated in granulocytes of
      all PNH patients analyzed so far. In contrast, significant upregulation of
      TAXREB107 is present only in some of our PNH patients. Further analysis confirmed
      their overexpression in PNH and excluded a possible secondary event character of
      observed overexpression. Moreover, similar levels of expression in cases of other
      clonal diseases, such as MPS and MDS, has been identified. CONCLUSION: Our data
      suggest that additional genetic alterations apart from PIG-A mutations could be
      present in PNH granulocytes. In addition, these genetic changes might contribute
      to clonal expansion of GPI-deficient cells in PNH.

PMID- 11823034
TI  - CpG island methylation of the hTERT promoter is associated with lower telomerase
      activity in B-cell lymphocytic leukemia.
AB  - OBJECTIVE: Expression of the catalytic subunit of the telomerase enzyme hTERT is
      essential for prolonging the replicative lifespan and is the rate-limiting step
      in cellular immortalization and carcinogenesis. Because hTERT expression is
      positively correlated with telomerase activity, its regulation is suggested as
      the major determinant of enzymatic activity. The hTERT promoter region contains
      two CpG islands, which are known to be target sites for de novo DNA methylation.
      To elucidate the impact of this epigenetic mechanism on telomerase activity, we
      analyzed the degree of hTERT promoter methylation in 30 patients with B-cell
      chronic lymphocytic leukemia. MATERIALS AND METHODS: hTERT promoter methylation
      was assessed using a methylation-specific competitive polymerase chain reaction
      assay. The assay is based on digestion of genomic DNA with a methylation
      sensitive restriction enzyme before amplification with an internal standard.
      RESULTS: Patients exhibiting high telomerase activity showed significantly less
      methylation of the hTERT promoter core domain than patients with low enzyme
      activity. In addition, telomerase activity was significantly associated with
      telomere length and overall survival. CONCLUSIONS: Our data show that the degree
      of CpG island methylation of the hTERT promoter exhibits an impact on telomerase
      activity in a subgroup of patients with B-cell chronic lymphocytic leukemia and
      therefore is assumed to play a role in regulating hTERT gene expression in these
      patients.

PMID- 11823035
TI  - Heparanase expression in human leukemias is restricted to acute myeloid
      leukemias.
AB  - OBJECTIVE: Matrix metalloproteinases and an endo-beta-D-glucuronidase
      (heparanase) are enzymes that degrade the protein and carbohydrate constituents
      of basement membranes, thereby facilitating transendothelial migration of blood
      borne cells. Heparanase activity was found to correlate with the metastatic
      potential of solid tumors. We evaluated heparanase expression, at the levels of
      gene and protein expression and activity in a variety of leukemias, and compared
      it with normal hematopoietic cells. MATERIALS AND METHODS: Heparanase expression
      was evaluated in leukocytes isolated from peripheral blood of 71 patients with
      myeloid and lymphoid leukemias, or non-Hodgkin's lymphoma. Analysis was performed
      at two levels: heparanase RNA was determined by reverse transcriptase polymerase
      chain reaction, and heparanase protein was evaluated by immunocytochemistry and
      flow cytometry. RESULTS: In eight peripheral blood samples from normal donors,
      heparanase RNA was detected, and protein was found within the cytoplasm of
      granulocytes. In mononuclear cells derived from various leukemias, heparanase RNA
      was expressed in 14 of 15 acute myeloid leukemia (AML) samples. In contrast,
      cells derived from all 33 chronic lymphoblastic leukemia, all 7 non-Hodgkin's
      lymphoma, 7 of 8 chronic myeloid leukemia, and 6 of 8 acute lymphoblastic
      leukemia patients showed no detectable expression of the heparanase RNA.
      Heparanase protein was detected primarily within the cytoplasm of AML cells,
      indicating that the enzyme is produced and stored within the cytoplasm of myeloid
      cells, with limited expression on the cell surface. CONCLUSION: We propose that
      heparanase expression is associated with the myeloid lineage and may serve as an
      independent marker to support the identification of AMLs.

PMID- 11823036
TI  - Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong
      skin graft survival in vivo.
AB  - OBJECTIVE: Mesenchymal stem cells (MSCs), multipotential cells that reside within
      the bone marrow, can be induced to differentiate into various components of the
      marrow microenvironment, such as bone, adipose, and stromal tissues. The bone
      marrow microenvironment is vital to the development, differentiation, and
      regulation of the lymphohematopoietic system. We hypothesized that the activities
      of MSCs in the bone marrow microenvironment might also include immunomodulatory
      effects on lymphocytes. METHODS: Baboon MSCs were tested in vitro for their
      ability to elicit a proliferative response from allogeneic lymphocytes, to
      inhibit an ongoing allogeneic response, and to inhibit a proliferative response
      to potent T-cell mitogens. In vivo effects were tested by intravenous
      administration of donor MSCs to MHC-mismatched recipient baboons prior to
      placement of autologous, donor, and third-party skin grafts. RESULTS: MSCs failed
      to elicit a proliferative response from allogeneic lymphocytes. MSCs added into a
      mixed lymphocyte reaction, either on day 0 or on day 3, or to mitogen-stimulated
      lymphocytes, led to a greater than 50% reduction in proliferative activity. This
      effect could be maximized by escalating the dose of MSCs and could be reduced
      with the addition of exogenous IL-2. In vivo administration of MSCs led to
      prolonged skin graft survival when compared to control animals: 11.3 +/- 0.3 vs 7
      +/- 0. CONCLUSIONS: Baboon MSCs have been observed to alter lymphocyte reactivity
      to allogeneic target cells and tissues. These immunoregulatory features may prove
      useful in future applications of tissue regeneration and stem cell engineering.

PMID- 11823037
TI  - Differential expression of Hox, Meis1, and Pbx1 genes in primitive cells
      throughout murine hematopoietic ontogeny.
AB  - OBJECTIVE: The Hox gene family of transcription factors is thought to be involved
      in the regulation of primitive hematopoietic cells, including stem cells and
      early committed progenitors, and has also been directly implicated in leukemia.
      To gain further insight into Hox gene-mediated regulation of hematopoiesis, we
      investigated the expression pattern of representative Hox genes and two of their
      cofactors, Pbx1 and Meis1, at different stages of murine hematopoiesis. METHODS:
      Functionally distinct subpopulations of murine bone marrow (BM) and fetal liver
      day 14.5 (FL) cells were isolated by flow cytometry, and gene expression of
      various homeobox-containing genes was assessed by global cDNA amplification
      technique. RESULTS: Hox genes were found preferentially expressed in
      hematopoietic stem cell (HSC)-enriched subpopulations and downregulated following
      differentiation and maturation. This profile of expression was observed at both
      adult and fetal stages of hematopoiesis. The Pbx1 and Meis1 genes had important
      differences in their expression pattern but were both detected in Hox expressing
      subpopulations. In particular, Meis1 consistently showed an expression profile
      closely resembling that of Hox genes. Finally, using the in vitro embryonic stem
      (ES) cell differentiation model to mimic embryonic hematopoiesis, we found
      coexpression of Hox genes and their cofactors coincided with the appearance of
      hematopoietic progenitor cells. CONCLUSION: Together, these results further
      support the notion that Hox genes are involved in the regulation of early
      hematopoietic cells and provide strong evidence that they are involved in the
      regulation of hematopoiesis throughout ontogeny.

PMID- 11823038
TI  - Comparative gene expression in hematopoietic progenitor cells derived from
      embryonic stem cells.
AB  - OBJECTIVE: The aim of this study was to characterize at the molecular level the
      hematopoietic progenitor cells derived from rhesus monkey embryonic stem (ES)
      cell differentiation. MATERIALS AND METHODS: We purified CD34(+) and CD34(+)CD38(
      ) cells from rhesus monkey ES cell cultures and examined the expression of a
      variety of genes associated with hematopoietic development, by semiquantitative
      polymerase chain reaction analysis. For comparison, we examined cell preparations
      from fresh or cultured rhesus monkey bone marrow (BM) and from mouse ES cells and
      BM. RESULTS: We observed a high degree of similarity in the expression patterns
      of these genes, with only a few exceptions. Most notably, the message of the flt3
      gene was undetectable in rhesus monkey ES cell-derived CD34(+) and CD34(+)CD38(-)
      cells, whereas substantial flt3 expression was observed in the corresponding
      cells from fresh BM and in CD34(+) cells from cultured BM. The integrin alphaL
      and interleukin-6 (IL-6) receptor genes also were expressed in CD34(+)CD38(-)
      cells from BM, but there was little or no expression of these genes in
      CD34(+)CD38(-) cells derived from ES cells. Parallel analyses, using CD34(+)Lin(
      ) cells derived from murine ES cell cultures, showed no apparent expression of
      flt3, integrin alphaL, or IL-6 receptor, whereas corresponding cell preparations
      isolated from mouse BM expressed high levels of all of these genes. CONCLUSIONS:
      ES cell-derived hematopoietic progenitors, both from the rhesus monkey and from
      the mouse, exhibited the same alterations in gene expression compared with BM
      derived cells from these animals. These observations could reflect the presence
      of different subpopulations in the cell fractions that were compared, or they may
      represent altered biologic properties of ES cell-derived hematopoietic stem
      cells.

PMID- 11823039
TI  - Hypoxia maintains and interleukin-3 reduces the pre-colony-forming cell potential
      of dividing CD34(+) murine bone marrow cells.
AB  - OBJECTIVE: The aim of this study was to determine whether the combination of a
      sizable generation of colony-forming cells (CFC) with the maintenance of their
      progenitors (pre-CFC) ensured by incubation in hypoxia is associated with a
      certain degree of cell cycling, ultimately responsible for "self-renewal" of pre
      CFC. The effects of interleukin-3 (IL-3) on the cycling and CFC-generation
      potential of pre-CFC also was investigated. MATERIALS AND METHODS: In severely
      hypoxic (0.9% O(2)) murine bone marrow cell cultures containing stem cell factor,
      interleukin-6, and granulocyte colony-stimulating factor, pre-CFC maintenance was
      characterized by the culture-repopulating ability assay, an in vitro analogue of
      the marrow-repopulating ability assay. The proliferative history of CD34(+) cells
      in primary cultures was determined by PKH2 staining and related to their CFC
      generation potential. In some experiments, subsets of CD34(+) cells sorted on the
      basis of the number of cell divisions (0, 1, >1) were independently
      characterized. RESULTS: In hypoxia, the numbers of CFC and CD34(+) cells were
      markedly reduced, whereas pre-CFC were maintained better than in air. Addition of
      5-fluorouracil to hypoxic cultures for 2 days suppressed their CFC-generation
      potential. The CFC-generation potential of divided CD34(+) cells was maintained
      or increased with respect to that of undivided cells in hypoxia but not in air.
      IL-3 decreased CFC-generation potential at both oxygen concentrations. IL-3 also
      increased the number of CD34(+) cells that divided more than once in hypoxia,
      decreasing their CFC-generation potential. CONCLUSIONS: Maintenance of CFC
      generation potential in hypoxia occurs mainly in a subset of cycling progenitors,
      despite their proliferation (self-renewal). IL-3 decreased CFC-generation
      potential by increasing the rate of pre-CFC proliferation beyond the first cycle,
      which probably results in their differentiation and loss of CFC-generation
      potential.

PMID- 11823040
TI  - Frequency and differentiation capacity of circulating LTC-IC mobilized by G-CSF
      or GM-CSF following chemotherapy: a comparison with steady-state bone marrow and
      peripheral blood.
AB  - OBJECTIVE: The present study was designed to compare directly the frequency of
      circulating LTC-IC and E-LTC-IC mobilized in peripheral blood (PB) after
      chemotherapy supported by either G-CSF (PB-G) or GM-CSF (PB-GM) in comparison to
      steady-state bone marrow (BM) and PB (PB-ST) values in the same patients.
      MATERIALS AND METHODS: Long-term cultures (LTC) were performed from 20 patients
      with malignant lymphoma at saturating cell concentrations to assess bulk
      progenitor cell production and by limiting dilution assay (LDA) to measure both
      frequency of LTC-IC and their proliferative and differentiation capacities.
      RESULTS: While CFC production in bulk LTC was higher at weeks 3-5 with PB-G than
      with PB-GM samples, week-5 LTC-IC and week-10 LTC-IC (E-LTC-IC) frequencies were
      not different using a LDA. However, the number of CFC derived from a single LTC
      IC was higher in PB-G patients than in PB-GM patients (p = 0.01). Interestingly,
      the frequency of LTC-IC per 1 x 10(5) MNC in mobilized PB positively correlated
      with one-year marrow progenitor cell recovery, in contrast to the number of
      autografted CD34(+) cells and CFU-GM per kg. CONCLUSION: Both G-CSF and GM-CSF
      resulted in similar increases in LTC-IC and E-LTC-IC in PB at comparable levels
      to those present in BM. However, the differentiation capacity of LTC-IC was
      higher after mobilization with G-CSF than with GM-CSF, suggesting qualitative
      differences in LTC-IC mobilized with these growth factors.

PMID- 11823041
TI  - Efficacy and safety of CD34-selected and CD19-depleted autografting in multiple
      myeloma patients: a pilot study.
AB  - OBJECTIVE: If multiple myeloma patients are to be cured after high-dose treatment
      supported by autologous stem cell transplantation, grafts must be purged of
      circulating myeloma cells. Myeloma cells are present in all grafts and have been
      identified as CD38(++)CD45(-) plasma cells, plasma blasts, and CD19(+) B cells.
      MATERIALS AND METHODS: In an attempt to improve the purging strategy, we studied
      a two-step procedure consisting of CD34(+) enrichment followed by CD19 depletion.
      This article describes the evaluation of this sequential magnetic microbead
      selection after 18 procedures in 14 patients. RESULTS: The processed autografts
      contained a median CD34 purity of 81% (range 21-99%) and a recovery of 47% (range
      15-82%). Flow cytometric analysis documented the expected reduction of CD34(-) B
      cells and plasma cells, in most cases to a level below the sensitivity of flow
      cytometry. Real-time reverse transcriptase polymerase chain reaction documented a
      CD19 mRNA relative reduction to 0.042 (range 0.01-0.21). Allele-specific
      oligonucleotide IgH primers were designed for five patients. All products were
      positive for clonal myeloma cells before processing, but only 1 of 5 was negative
      after the procedure. The clinical outcome after reinfusion of the processed
      autografts was evaluated by blood cell recovery and found to be within the range
      expected from engraftment of unmanipulated autografts. One patient who had
      delayed platelet recovery associated with cytomegalovirus infection recovered
      after anti-cytomegalovirus treatment. CONCLUSIONS: This pilot study documented
      engraftment after reinfusion of CD34-selected and CD19-depleted autografts.
      However, one patient suffered from unexpected prolonged thrombocytopenia. The
      efficacy of the procedure was evaluated and reduction of myeloma cells was
      indicated, with only one autograft free of clonal cells.

PMID- 11823042
TI  - Nonmyeloablative allogeneic bone marrow transplantation as immunotherapy for
      hematologic malignancies and metastatic solid tumors in preclinical models.
AB  - OBJECTIVE: We previously demonstrated that a combination of mild total lymphoid
      irradiation (TLI) with selective depletion of the host's donor-reactive cells
      allows for stable and graft-vs-host disease (GVHD)-free engraftment of allogeneic
      bone marrow (BM). In this study, we investigated the efficacy of this
      nonmyeloablative strategy for BM transplantation (BMT) as immunotherapy for
      minimal residual disease. MATERIALS AND METHODS: BALB/c mice inoculated with
      leukemia (BCL1) or breast carcinoma (4T1) cells were conditioned for BMT with TLI
      (200 cGy) followed by priming with donor (C57BL/6) BM cells on day 1, and by
      injection with 200 mg/kg cyclophosphamide on day 2. After conditioning (day 3),
      recipients were transplanted with BM cells from the same donor. Treated animals
      were monitored for 230 days for survival, development of leukemia/solid tumor,
      and GVHD. RESULTS: BMT converted the mice to complete chimeras and prevented
      development of leukemia in 90% of recipients and locally growing breast carcinoma
      in 40% of the mice. Immunization of donors of the second BM with 4T1 cells
      prevented development of breast carcinoma in 80% of 4T1 inoculated mice. Fewer
      animals treated for malignancy by nonmyeloablative BMT died of GVHD than those
      treated by myeloablative BMT. However, late GVHD-related mortality in mice
      treated for leukemia was higher than after nonmyeloablative BMT to naive
      recipients (p < 0.00001). Infusion of host-type anti-donor immune lymphocytes 8
      days after BMT improved the survival of recipients treated for leukemia without
      affecting engraftment and the graft-vs-leukemia potential of donor BM.
      CONCLUSIONS: Effective eradication of malignant cells can be achieved following
      allogeneic BMT after nonmyeloablative conditioning.

PMID- 11823044
TI  - The postgenomic age: characterization of proteomes.
AB  - Global analysis of biological systems is becoming increasingly feasible as
      technologies that facilitate genome-wide analyses of gene expression are
      developed. Proteomics is the global analysis of expressed proteins (including
      posttranslational modifications) and seeks to establish the relationship between
      genome sequence, expressed proteins, protein-protein interactions, and cell and
      tissue phenotype. While the relative abundance of transcripts can be quantified
      using gene expression microarrays, the identification and quantitation of
      expressed proteins is more challenging. Nevertheless, the potential payoff for
      global protein analyses is immense because identification of distinctive protein
      signatures associated with cell function may provide novel therapeutic targets,
      molecular markers of disease, and increased understanding of determinants of cell
      phenotype. The challenges and promises of applications of established and
      emerging proteome strategies to detect and quantify differentially expressed
      proteins in culture cells are discussed.

PMID- 11823045
TI  - Transient detection of beta-galactosidase activity in hematopoietic cells,
      following reinjection of retrovirally marked autologous blood progenitors in
      patients with breast or ovarian cancer receiving high-dose chemotherapy.
AB  - OBJECTIVE: The aim of this report is to demonstrate the feasibility and safety of
      genetically modifying autologous human blood CD34(+) cells in vitro, with a
      retroviral vector that encodes a marker gene. The fate of genetically modified
      cells and their progeny was followed in vivo, after reinfusion in patients
      treated with high-dose chemotherapy for poor-prognosis breast or ovarian
      carcinomas. PATIENTS AND METHODS: Six patients received genetically modified
      autologous peripheral blood progenitors, together with unmanipulated aphereses,
      following high-dose chemotherapy. CD34(+) cells were immunoselected from
      aphereses, and retrovirally transduced by coculture with the retroviral vector
      producing cell line, to express a nuclear localized version of E. coli beta
      galactosidase, encoded by a defective Moloney-murine leukemia virus-derived
      retroviral vector. Cells were reinfused to the patients after myeloablation,
      without prior ex vivo selection. RESULTS: Five out of six patients showed the
      transient presence of low numbers of beta-galactosidase(+) cells, as detected
      with an immunocytochemical assay, in the peripheral blood, during the first month
      following infusion. One patient had beta-galactosidase(+) clonogenic progenitors
      in her marrow at two months after transplantation, including HPP-CFC;
      intriguingly, this patient had the lowest percentage of X-gal(+) cells in her
      graft. Patients experienced side effects that are often observed after high-dose
      chemotherapy. CONCLUSIONS: Feasibility and safety of genetic modification of
      human hematopoietic stem and progenitor cells are demonstrated by this study. Ex
      vivo or in vivo selection is not mandatory, even in clinical situations where
      transduced cells have no survival advantage over wild-type cells; however,
      significant improvements in gene transfer technology are needed to achieve
      potentially useful levels of expression in such clinical situations.

PMID- 11823046
TI  - Somatostatin is a selective chemoattractant for primitive (CD34(+)) hematopoietic
      progenitor cells.
AB  - OBJECTIVE: Somatostatin (SST) is a regulatory peptide with a wide variety of
      activities in different tissues. SST activates G(alpha i)-protein-coupled
      receptors of a family comprising five members (SSTR1-5). Despite the broad use of
      SST and its analogs in clinical practice, the spectrum of activities of SST is
      incompletely defined. Here, we examined the role of SST and its receptors in
      hematopoiesis. MATERIALS AND METHODS: SSTR expression on human and mouse
      hematopoietic cells was analyzed by flow cytometry and reverse transcriptase
      polymerase chain reaction. The effects of SST on cell migration were measured in
      transwell assays. Using selective inhibitors, signaling mechanisms involved in
      SSTR2-mediated migration were studied in 32D cell transfectants expressing SSTR2.
      RESULTS: Human hematopoietic cells exclusively expressed SSTR2, whereas mouse
      bone marrow cells expressed SSTR2 and SSTR4. SSTR levels were high on primitive
      (CD34(+), Lin(-)) but low or absent on more mature (CD34(-), Lin(+)) cell types.
      Both SST and its analog octreotide acted as chemoattractants for primitive
      hematopoietic cells. Despite the presence of SSTR4, bone marrow cells from SSTR2
      deficient mice failed to migrate toward SST gradients, suggesting that SSTR2 and
      SSTR4 are functionally different in this respect. SST activated
      phosphatidylinositol 3-kinase and the MAP kinases Erk1/2 and p38 in 32D[SSTR2]
      cells. While chemical inhibitors of these kinases had some effect, SST-induced
      migration was most strongly affected by blocking G(alpha i) activity or by
      elevating intracellular cAMP levels. CONCLUSIONS: Somatostatin acts as a
      selective chemoattractant for immature hematopoietic cells via activation of
      multiple intracellular pathways.

PMID- 11823047
TI  - Expression of CD86 in acute myelogenous leukemia is a marker of
      dendritic/monocytic lineage.
AB  - OBJECTIVE: The aim of this study was to determine whether expression of the CD86
      costimulatory molecule in acute myeloid leukemia (AML) can identify blast cells
      committed to the monocytic/dendritic lineage. MATERIAL AND METHODS: One hundred
      ten consecutive AML patients observed at diagnosis were studied by flow
      cytometry. In selected experiments, in vitro cultures with CD34(+)CD86(+) or
      CD34(-)CD86(+) blasts were performed in the presence of granulocyte-macrophage
      colony-stimulating actor (GM-CSF) with or without tumor necrosis factor-alpha
      (TNF-alpha) or GM-CSF + interleukin-4 (IL-4), respectively, to induce a dendritic
      differentiation, documented by morphologic and immunophenotypic assays. T-cell
      alloreactivity to CD86(+) AML cells and leukemic dendritic cells (AML-DC) was
      tested in mixed leukocyte cultures and anti-leukemic cytotoxic assays. RESULTS:
      CD86 was expressed in 54% AML, whereas CD80 and CD1a were only occasionally
      positive. CD86(+) AML samples included M5 and M4, but also 47% M0-M1 FAB types,
      and were more frequently CD14(+) (p < 0.00001) and CD34(-) (p = 0.00005) than
      CD86(-)AML. Six different patterns of CD86(+) AML were identified, according to
      CD34 or CD14 total or partial coexpression. Four samples enriched in
      CD34(+)CD86(+) AML cells differentiated into AML-DC CD86(+), CD80(+), CD40(+),
      CD11c(+), HLA-DR(++), CD14(+/-) that also were CD1a(+) or CD83(+), after 6 days
      of in vitro culture with GM-CSF +/- TNF-alpha. CD34(-)CD86(+) AML cells
      differentiated into AML-DC after 3 to 5 days (n = 5 experiments), and trisomy 8
      was found in two AML and AML-DC samples by fluorescence in situ hybridization
      analysis. Finally, AML-DC induced more potent allo-T-cell proliferation, cytokine
      release, and anti-leukemic cytotoxicity than CD86(+) blasts. CONCLUSIONS: In AML,
      CD86 is a marker of monocytic/dendritic lineage. Because CD86(+) blasts may
      differentiate into DC rapidly, CD86(+)AML patients could be optimal candidates
      for immunotherapy studies, both in autologous and allogeneic settings.

PMID- 11823048
TI  - BLyS and BLyS receptor expression in non-Hodgkin's lymphoma.
AB  - OBJECTIVE: B Lymphocyte Stimulator (BLyS) protein and its receptor are new
      members of the tumor necrosis factor family, with specific effects exclusively on
      B cells. We have studied the tumor cell expression of the BLyS-Receptor (BLyS-R)
      and the serum BLyS protein levels in patients with different types of non
      Hodgkin's lymphomas (NHL). METHODS: BLyS-R expression was assessed by flow
      cytometry on B cells from 43 NHL patients and 10 normal donors. BLyS protein
      serum levels were analyzed by ELISA. RESULTS: All B cells, tumor and normal,
      expressed BLyS-R. The mean fluorescence intensity (MFI +/- SD) of BLyS-R on
      normal B cells was 25.2 +/- 2.3 arbitrary units, while follicular NHL and chronic
      lymphocytic leukemia (CLL) exhibited significantly lower expression of the BLyS-R
      (17.7 +/- 3.1; 15.5 +/- 3.9, respectively, p < 0.0001 for both); other lymphoma
      subtypes expressed levels comparable to normal B cells (diffuse large cell, 24.8
      +/- 4.3; mantle cell, 20 +/- 4.7; marginal zone, 20.7 +/- 3.7). BLyS protein
      serum levels were analyzed in 15 normal donors and 17 patients with follicular
      NHL. Levels of BLyS protein were, on average, threefold higher in patients with
      follicular lymphoma compared to normal donors (mean +/- SD; 13.4 +/- 5.6 ng/mL vs
      4.6 +/- 0.7 ng/mL; p < 0.0001). BLyS protein alone was unable to stimulate
      proliferation in cultures of follicular lymphoma B cells or normal B cells.
      CONCLUSION: The specificity of the expression of BLyS-R by B-cell lymphomas opens
      new opportunities for the treatment of these cancers by targeting this ligand
      receptor pair.

PMID- 11823049
TI  - Leukemic predisposition of pSca-1/Cb2 transgenic mice.
AB  - OBJECTIVE: The gene encoding the peripheral cannabinoid receptor Cb2 is located
      in the common virus integration site Evi11 and is associated with hematopoietic
      malignancies in mice. To determine the effect of Cb2 overexpression on
      hematopoietic development in vivo, Cb2 transgenic mice were generated. MATERIALS
      AND METHODS: A Cb2 expression vector was constructed containing a Cb2 cDNA
      fragment cloned into the 14kb Sca-1 (Ly-6E.1) gene. Two transgenic lines in which
      Cb2 expression is controlled by the Sca-1 promoter were generated, and the effect
      on hematopoietic development was studied. Expression of Cb2 mRNA or protein was
      studied by RNase protection analysis and ligand binding assays, respectively.
      Leukemic predisposition was investigated by injecting newborn transgenic as well
      as control animals with Cas-Br-M murine leukemia virus (Cas-Br-M MuLV). RESULTS:
      Although increased expression of the Cb2 gene was observed in hematopoietic
      tissues, follow-up of more than 1 year did not reveal any hematologic defect.
      Interestingly, infection of newborn pSca-1/Cb2 transgenic mice with Cas-Br-M MuLV
      revealed that significantly more transgenic mice developed leukemia than virus
      treated control littermates. Because these studies provide evidence for the
      cooperative potential of Cb2 in leukemia progression, we wished to identify genes
      that may collaborate with Cb2 in leukemic transformation. Our study suggests that
      Evi1, another common target for proviral integration in mouse leukemias, may be
      overexpressed in virus-induced leukemias in pSca-1/Cb2 transgenic mice.
      CONCLUSIONS: The data indicate that hematopoietic precursor cells that express
      high levels of Cb2 possess increased susceptibility for leukemia development and
      that Cb2 and Evi1 might collaborate in leukemogenesis.

PMID- 11823050
TI  - Down-regulation of retroviral transgene expression during differentiation of
      progenitor-derived dendritic cells.
AB  - OBJECTIVE: Hematopoietic progenitor cells are a promising source for generation
      of genetically modified dendritic cells. A prerequisite for using these cells in
      therapeutic approaches is stable vector-mediated transgene expression during and
      after cell maturation. We investigated the expression of enhanced green
      fluorescence protein (EGFP) mediated by retroviral vectors in dendritic cells and
      other hematopoietic cells differentiated in vitro. MATERIAL AND METHODS: CD34(+)
      cells were efficiently transduced with retroviral vector constructs known to
      mediate different expression levels due to distinct cis-acting elements. EGFP(+)
      cells were purified by cell sorting and differentiated to monocytes,
      granulocytes, dendritic cells, and erythrocytes. Coexpression of EGFP and cell
      type-specific markers was analyzed by flow cytometry. RESULTS: Transgene
      expression from various retroviral vectors was silenced exclusively in dendritic
      cells, but not in other mature myeloid cells. Loss of EGFP was most pronounced in
      cells initially displaying low expression levels. This was confirmed by using a
      retroviral vector coding for a variant of EGFP with significantly reduced half
      life. In contrast, a majority of dendritic cells showed stable expression when a
      self-inactivating retroviral construct using an internal cytomegalovirus promotor
      was used. CONCLUSIONS: We suggest that expression from the retroviral long
      terminal repeat is silenced during dendritic cell differentiation in vitro. High
      levels of stable transgene product in progenitor cells may mask a loss of
      expression. An improvement of retroviral vectors mediating stable transgenic
      expression is necessary for therapeutic approaches using gene-modified dendritic
      cells.

PMID- 11823051
TI  - Modulation of MDM2/p53 and cyclin-activating kinase during the megakaryocyte
      differentiation of human erythroleukemia cells.
AB  - OBJECTIVE: This study was undertaken to address the involvement of CDK activating
      kinase (CAK), p53, and MDM2 proteins in the mitotic arrest associated with the
      acquisition of a polyploid DNA content during megakaryocyte differentiation of
      human erythroleukemia (HEL) cells. METHODS: To evaluate this mechanism we
      investigated HEL cells as a model system in which there is a marked increase in
      DNA content during megakaryocyte differentiation induced by phorbol-diesters.
      Specific cell-cycle phases were separated by centrifugal elutriation and SDS PAGE
      and Western analysis were performed to determine the relative abundance of these
      proteins. Kinase assays were carried out following immunoprecipitation of
      cellular lysates with the antibodies to the proteins. RESULTS: Polyploid HEL
      cells show an increase in the abundance of the CAK complex proteins, CDK7 and
      cyclin H, and a sixfold increase in CAK-specific activity. Increased CAK activity
      in polyploid HEL cells follows both the downregulation of p53 protein and its
      decreased association with CAK complex. Consistent with the reduction of p53,
      polyploid HEL cells undergo a dramatic increase in MDM2 protein abundance that in
      turn facilitates increased interaction of this protein with p53. CONCLUSION:
      These observations demonstrate that deregulated expression of MDM2 and p53 during
      megakaryocyte differentiation allow a relaxation of the control over genomic
      stability, allowing further replicative rounds of DNA synthesis.

PMID- 11823052
TI  - MplK, a natural variant of the thrombopoietin receptor with a truncated
      cytoplasmic domain, binds thrombopoietin but does not interfere with
      thrombopoietin-mediated cell growth.
AB  - OBJECTIVE: Interaction of thrombopoietin (TPO) with its receptor c-Mpl is
      responsible for the formation of megakaryocytes and platelets. In humans, there
      are two major c-mpl molecules, MplP and MplK, which are generated by alternative
      splicing. In contrast to MplP, MplK has none of the intracellular sequences
      required for typical signal transduction but instead has a unique 27 amino acid
      sequence that is coded by intron 10. We tested to determine if MplK exerts a
      negative effect on TPO Mpl signal transduction by interfering with the normal
      homodimerization of MplP. MATERIALS AND METHODS: A cassette coding for MplK cDNA
      was introduced into parental and MplP-expressing BaF3 cells and TPO-mediated cell
      growth studied. RESULTS: Cells expressing MplK alone did not respond to TPO
      compared to cells that expressed MplP. When MplK was coexpressed with MplP on the
      cell surface of BaF3, no modification in cell growth was observed when compared
      to those expressing MplP alone. To determine if the normal homodimerization
      process was negatively influenced, two genetically engineered variants of c-Mpl,
      one lacking the box1 sequence and the other containing only the first nine amino
      acids of the intracellular domain, were introduced into MplP-expressing cells. In
      contrast to MplK, these mutants had a dominant negative effect on TPO-mediated
      cell growth. CONCLUSIONS: MplK does not influence TPO-mediated growth of Mpl
      expressing cells. Our data suggest that the absence of a dominant negative effect
      of MplK most probably is due to the inability of MplK to dimerize with the MplP
      receptor.

PMID- 11823053
TI  - Changes in integrin expression are associated with altered homing properties of
      Lin(-/lo)Thy1.1(lo)Sca-1(+)c-kit(+) hematopoietic stem cells following
      mobilization by cyclophosphamide/granulocyte colony-stimulating factor.
AB  - OBJECTIVE: Although migration of hematopoietic stem cells (HSC) is essential for
      normal hematopoiesis and successful hematopoietic cell transplantation, little is
      known about the mechanisms that underlie this movement. We have sought to
      characterize the factors that regulate HSC migration by analyzing changes in
      expression of particular adhesion receptors associated with
      cyclophosphamide/granulocyte colony-stimulating factor (Cy/G-CSF)-induced HSC
      mobilization. METHODS: Expression by Lineage(-/lo)Thy1.1(lo)Sca-1(+)c-kit(+) HSC
      of members of the beta1 integrin family of adhesion molecules was assessed in
      untreated or Cy/G-CSF-treated mice by multiparameter flow cytometry. In parallel,
      the in vivo homing properties of normal and mobilized HSC were compared following
      intravenous transfer of fluorescently marked HSC. RESULTS: Normal adult HSC
      express high levels of several beta1 integrin family members. Following Cy/G
      treatment, bone marrow HSC selectively downregulate alpha 2 integrin expression
      and upregulate alpha 5 expression. HSC found in the blood following Cy/G-CSF
      treatment express significantly lower levels of multiple integrins than their
      bone marrow and/or splenic counterparts. Changes in integrin expression by blood
      borne HSC correlate with a 50% decrease in their ability to home to the bone
      marrow in short-term assays, and with previously observed defects in competitive
      engraftment by these HSC. Similar reductions in bone marrow (BM) homing are
      observed for BM HSC treated with alpha 4 integrin function blocking mAb prior to
      injection. Modulation of integrin expression induced by mobilization was not
      associated with cell-cycle progression. CONCLUSION: Changes in integrin
      expression and function are associated with HSC mobilization and likely
      significantly affect the engraftment potential of hematopoietic stem cells.

PMID- 11823054
TI  - Plasticity in the projection from the anterior thalamic nuclei to the anterior
      cingulate cortex in the rat in vivo: paired-pulse facilitation, long-term
      potentiation and short-term depression.
AB  - Several neurophysiological and computational theories of the rodent navigational
      system suggest that the differing cortices of the frontal lobe and thalamus share
      information and therefore undergo changes in synaptic strength. We examine here
      for the first time three forms of synaptic plasticity in the projection from the
      anterior thalamic nuclei to the anterior cingulate cortex: we demonstrate that
      this projection is capable of expressing paired-pulse facilitation, long-term
      potentiation, and short-term depression. Furthermore, input/output curves show
      that field excitatory post-synaptic potential amplitude increased at all stimulus
      intensities following high-frequency stimulation. These findings add important
      information to our understanding of synaptic plasticity in this important
      pathway, which has been widely hypothesized to play important roles in memory and
      spatial representation in the rodent.

PMID- 11823055
TI  - Expression of Ca2+/calmodulin-dependent protein kinase (CaMK) Ibeta2 in
      developing rat CNS.
AB  - We observed the onset time and distribution pattern of beta2 isoform of
      Ca2+/calmodulin-dependent protein kinase I (CaMKIbeta2) in the CNS of the rat
      during the embryonic period until birth using an immunohistochemical method. The
      expression of CaMKIbeta2 started at embryological day 10 when the three primary
      brain vesicles and neural tube are generated from the neural plate. During the
      embryonic period, highly immunoreactive products were ubiquitously detected in
      neurons in the CNS, although neurons in the caudate-putamen and globus pallidus
      were faintly immunostained or immunonegative. High expression of CaMKIbeta2
      persisted in the olfactory bulb, lymbic system, neocortex, septal nuclei,
      amygdala complex, some hypothalamic nuclei, pontine nuclei, Purkinje cells and
      granule cells in the cerebellar cortex through the developing period. At the
      subcellular level, CaMKIbeta2 was strongly expressed in nuclei of neurons but
      faintly in their cytoplasm, suggesting that this protein has an important role in
      the nuclear signaling pathway. This study demonstrates that expression of
      CaMKIbeta2 begins at the earliest developmental stage of the rat CNS and persists
      through the developing period.

PMID- 11823056
TI  - Arrestin2 and arrestin3 are differentially expressed in the rat brain during
      postnatal development.
AB  - Arrestins are adaptor proteins involved in homologous desensitization and
      trafficking of G protein-coupled receptors. Arrestins bind to activated
      phosphorylated receptors thus precluding further signal transduction. Two
      subtypes of non-visual arrestins, arrestin2 and arrestin3, have been cloned.
      Recently, specificity of various receptors to arrestins and differences in
      kinetics of receptor desensitization mediated by arrestins have been
      demonstrated. Both arrestins are expressed in the rat brain. However,
      quantitative assessment of their expression and detailed distribution are
      lacking. Here, we used quantitative ribonuclease protection assay and western
      blot to measure arrestin2 and arrestin3 mRNA and protein in the rat brain during
      postnatal development. In situ hybridization histochemistry was employed to study
      the detailed distribution of arrestin mRNAs in the adult and developing brain.
      Both arrestins were expressed from birth in all regions studied. Arrestin2 mRNA
      levels increased with development until the 14th postnatal day and then
      decreased, whereas arrestin2 protein levels continued to rise. Arrestin3 mRNA was
      maximal in neonates and then decreased, while arrestin3 protein changed little.
      In newborns and adults, the concentration of arrestin2 mRNA was two- to three
      fold higher than that of arrestin3. In neonates, the excess of the arrestin2
      protein over arrestin3 was commensurate with the excess of the arrestin2 mRNA
      (three-fold) but in the adult, the ratio was much higher (10-20-fold). Each
      arrestin demonstrated a unique distribution, although in many areas there was
      overlap suggesting co-localization. Both arrestins were highly expressed in the
      cortex and hippocampus. Arrestin2 was abundant in the thalamus, particularly in
      the anterior, intralaminar, and midline nuclei, while arrestin3 was abundant in
      the medial habenular. Arrestin3 was relatively abundant in most hypothalamic
      nuclei and extended amygdala. In the developing brain, arrestin3 was highly
      expressed in the subventricular zone, whereas arrestin2 was more abundant in
      differentiated areas. Our data demonstrate that arrestin2 is the major arrestin
      subtype in the rat brain, although arrestin3 is expressed in specific cell
      populations including postnatal proliferative zones. Because each arrestin
      appears to mediate receptor desensitization in a specific way, different kinetics
      of trafficking of the same receptor should be expected in different cells due to
      varying arrestin2/arrestin3 ratios. Thus, the response of receptors to specific
      drugs stimulating or blocking these receptors may depend on complement of
      arrestins in their target cells.

PMID- 11823057
TI  - Neurodegeneration in the Niemann-Pick C mouse: glial involvement.
AB  - A mouse model of Niemann-Pick type C disease has been found that exhibits
      neuropathology similar to the human condition. There is an age-related
      neurodegeneration in several brain regions and a lack of myelin in the corpus
      callosum in these mice. The purpose of the present study was to examine the
      Niemann-Pick mouse and determine whether: (1) microglia and astrocytes exhibit
      ultrastructural pathology similar to that found in neurons; (2) nerve fiber
      number is reduced when the myelin sheath is absent; and (3) the lysosomal
      hydrolase, cathepsin-D, is involved in the neurodegenerative process. Using light
      and electron microscopic methods, and immunocytochemistry, Niemann-Pick and
      control animals were examined at several ages. Cathepsin-D content was semi
      quantitatively measured in neurons and glial cells in brain regions known to
      exhibit neurodegeneration, as was the density of glial fibrillary acidic protein
      labeled astrocytes. The Niemann-Pick mouse exhibited: (1) an age-related increase
      in inclusion bodies in microglia and astrocytes, similar to that observed within
      neurons; (2) an almost complete absence of myelin in the corpus callosum by 7-8
      weeks of age, along with a 30% reduction in the number of corpus callosum axons;
      (3) a mild age-related increase in cathepsin-D content within nerve cells in many
      brain regions. However, the cathepsin-D elevation was greatest in microglial
      cells; (4) an age-related increase in the number of microglial cells containing
      intense cathepsin-D immunoreactivity in both the thalamus and cerebellum. Both of
      these brain regions have been shown previously to exhibit an age-related loss of
      neurons; and (5) an increase in the number of reactive astrocytes immunostained
      for glial fibrillary acidic protein, especially in the thalamus and cerebellum.
      These data indicate that glial cells are a major target for pathology in the
      Niemann-Pick mouse. The lack of myelin within the corpus callosum may be related
      to the loss of nerve fibers in this structure. The increase in cathepsin-D-laden
      microglial cells, in brain regions previously shown to undergo neurodegeneration,
      is consistent with a role for microglia in the phagocytosis of dead neurons and
      in actively contributing to the neurodegenerative process. The activation of
      astrocytes in regions that undergo neurodegeneration is also consistent with a
      role for these glial cells in the neurodegenerative process.

PMID- 11823058
TI  - Coexpression of the cannabinoid receptor type 1 with dopamine and serotonin
      receptors in distinct neuronal subpopulations of the adult mouse forebrain.
AB  - The cannabinoid receptor type 1 (CB1) displays unusual properties, including the
      dual capacity to inhibit or stimulate adenylate cyclase and a brain density
      considerably higher than the majority of G protein-coupled receptors. Together
      with overlapping expression patterns of dopamine and serotonin receptors this
      suggests a potential of CB1 to modulate the function of the dopamine and
      serotonin system. Indeed, pharmacological studies provide evidence for cross
      talks between CB1 and receptors of these neurotransmitter systems. In trying to
      obtain further insights into possible functional and/or structural interactions
      between CB1 and the dopamine receptors and the serotonin receptors, we performed
      double-label in situ hybridization at the cellular level on mouse forebrain
      sections by combining a digoxigenin-labelled riboprobe for CB1 with 35S-labelled
      riboprobes for dopamine receptors D1 and D2, and for serotonin receptors 5-HT1B
      and 5-HT3, respectively. As a general rule, we found that CB1 colocalizes with
      D1, D2 and 5-HT1B only in low-CB1-expressing cells which are principal projecting
      neurons, whereas CB1 coexpression with 5-HT3 was also observed in high-CB1
      expressing cells which are considered to be mostly GABAergic. In striatum and
      olfactory tubercle, CB1 is coexpressed to a high extent with D1, D2 and 5-HT1B.
      Throughout the hippocampal formation, CB1 is coexpressed with D2, 5-HT1B and 5
      HT3. In the neocortex, coexpression was detected only with 5-HT1B and 5-HT3. In
      summary a distinct pattern is emerging for the cannabinoid system with regard to
      its colocalization with dopamine and serotonin receptors and, therefore, it is
      likely that different mechanisms underlie its cross-talk with these
      neurotransmitter systems.

PMID- 11823059
TI  - Dendritic morphology of callosal and ipsilateral projection neurons in monkey
      prefrontal cortex.
AB  - Subpopulations of cortical pyramidal neurons have been distinguished based on the
      projection target of their principal axons or by their dendritic morphology. In
      this study, we sought to test the hypothesis that pyramidal neurons in monkey
      prefrontal cortex that furnish callosal or ipsilateral projections have
      distinctive dendritic morphologies. Retrogradely-labeled, Fast Blue-containing
      callosal and ipsilateral neurons were intracellularly filled with Lucifer Yellow,
      immunoconverted, and reconstructed. Quantitative measurements of the size and
      complexity of the dendritic arbor, including total dendritic length, horizontal
      extent, number of branch points, maximum branch order, and number of segments, as
      well as spine density, were made. In general, callosal neurons had larger and
      more complex dendritic arbors for both apical and basilar dendritic trees than
      did ipsilateral neurons. The greatest difference was in total dendritic length;
      the apical and basilar trees of callosal neurons were 34 and 25% longer,
      respectively. In addition, spine density was also significantly greater on the
      apical and basilar dendrites of callosal neurons. These findings could not be
      explained by differences in somal size or completeness of dendritic filling
      between callosal and ipsilateral neurons. Our observations support the hypothesis
      that callosal and ipsilateral neurons differ on a number of measures of dendritic
      size and complexity. Furthermore, these findings imply that these two
      subpopulations of pyramidal cells differ in the number and perhaps types of
      excitatory inputs that they receive. Finally, differences in the dendritic
      morphology of callosal and ipsilateral neurons have implications for
      understanding the functional attributes of these two populations of cells, as
      well as for the characterization of pyramidal neurons in human disease states.

PMID- 11823060
TI  - Effects of gonadectomy on immunoreactivity for choline acetyltransferase in the
      cortex, hippocampus, and basal forebrain of adult male rats.
AB  - Androgens are known to affect cognitive and mnemonic aspects of spatial
      processing. The cholinergic system is thought to play an important role in
      cognition and memory, but little is known about the interaction between androgen
      and cholinergic neurons. The present study focused on the effects of testosterone
      on the cholinergic neurons in the anterior cingulate cortex, the posterior
      parietal cortex, the hippocampus, and the basal forebrain including the medial
      septum, i.e., regions related to spatial processing. We examined choline
      acetyltransferase (ChAT) immunoreactivity in three groups of adult male rats:
      sham-operated (Sham), 28-day gonadectomized (GDX), and 28-day gonadectomized with
      immediate implantation of testosterone propionate (GDX+TP). Comparison of the
      Sham and GDX+TP groups demonstrated that the GDX group had significantly
      decreased cell counts of ChAT-immunoreactive neurons in anterior cingulate cortex
      layer II/III, posterior parietal cortex layer II/III, and the medial septum, but
      not in the other basal forebrain subregions examined (the horizontal part of the
      diagonal band of Broca and the substantia innominata). The GDX group also had
      significantly reduced hippocampal ChAT-immunoreactive fiber pixel density. The
      GDX+TP group maintained ChAT-immunoreactive cell counts in the anterior cingulate
      cortex, posterior parietal cortex, and medial septum equivalent to those in the
      Sham group. Less than 1% of identified cells showed colocalization of
      immunoreactivity for ChAT and androgen receptor in the cell bodies of the cortex
      and basal forebrain. Our observations demonstrate that the presence or absence of
      testosterone for 4 weeks influenced the cholinergic population region
      specifically in the adult rat brain.

PMID- 11823061
TI  - Neuroprotection and aging of the cholinergic system: a role for the ergoline
      derivative nicergoline (Sermion).
AB  - The aging brain is characterized by selective neurochemical changes involving
      several neural populations. A deficit in the cholinergic system of the basal
      forebrain is thought to contribute to the development of cognitive symptoms of
      dementia. Attempts to prevent age-associated cholinergic vulnerability and
      deterioration therefore represent a crucial point for pharmacotherapy in the
      elderly. In this paper we provide evidence for the protective effect of
      nicergoline (Sermion) on the degeneration of cholinergic neurons induced by nerve
      growth factor deprivation. Nerve growth factor deprivation was induced by
      colchicine administration in rats 13 and 18 months old. Colchicine induces a
      rapid and substantial down-regulation of choline acetyltransferase messenger RNA
      level in the basal forebrain in untreated adult, middle-aged and old rats.
      Colchicine failed to cause these effects in old rats treated for 120 days with
      nicergoline 10 mg/kg/day, orally. Moreover, a concomitant increase of both nerve
      growth factor and brain-derived neurotrophic factor content was measured in the
      basal forebrain of old, nicergoline-treated rats. Additionally, the level of
      messenger RNA for the brain isoform of nitric oxide synthase in neurons of the
      basal forebrain was also increased in these animals. Based on the present
      findings, nicergoline proved to be an effective drug for preventing neuronal
      vulnerability due to experimentally induced nerve growth factor deprivation.

PMID- 11823062
TI  - D-amphetamine-induced behavioral sensitization: effect of lesioning dopaminergic
      terminals in the medial prefrontal cortex, the amygdala and the entorhinal
      cortex.
AB  - The behavioral sensitization produced by the repeated administration of D
      amphetamine is known to involve dopaminergic neurons in the mesoaccumbens
      pathway. Induction of this process is dependent on action of the drug in the
      ventral tegmental area while its expression involves action in the nucleus
      accumbens. We studied here the putative involvement of dopaminergic projections
      other than the mesoaccumbens in this phenomenon. We examined the influence of
      dopaminergic lesion of the medial prefrontal cortex, the amygdala and the
      entorhinal cortex in the behavioral sensitization produced by repeated injections
      of amphetamine either peripherally or directly into the ventral tegmental area of
      the brain. The repeated administration of amphetamine induced a behavioral
      sensitization, with the ventral tegmental area a critical site for induction of
      the process. This sensitization to amphetamine cross-reacted with morphine and
      was still observed 2 weeks after cessation of the treatment. Bilateral 6
      hydroxydopamine lesion of dopaminergic terminals in either the medial prefrontal
      cortex or the amygdala, but not in the entorhinal cortex, prevented the
      development of behavioral sensitization to amphetamine and the cross
      sensitization with morphine, whether the amphetamine pretreatment was
      administered peripherally or directly into the ventral tegmental area. In
      conclusion, these results indicated that behavioral sensitization to amphetamine,
      which involves dopaminergic neurons of the ventral tegmental area, is also
      dependent on dopaminergic neurotransmission of the medial prefrontal cortex and
      amygdala but not of the entorhinal cortex.

PMID- 11823063
TI  - Sex differences in hippocampal slice excitability: role of testosterone.
AB  - In vivo fluctuations in gonadal hormones alter hippocampal excitability and
      modulate both physiological and pathological hippocampal processes. To assess
      hormonal effects on excitability within a functional hippocampal circuit,
      extracellular CA1 field responses were compared in slices from intact male,
      intact female, orchidectomized male, and ovariectomized female rats. Secondly,
      the effects of in vitro applications of 17-beta estradiol, progesterone, or
      testosterone on baseline excitability of slices from gonadectomized rats were
      assessed versus pre-hormone baseline measures. Finally, using the in vitro
      kindling model of slice epileptogenesis, steroid hormone effects on interictal
      like activity were also examined. Significant sex differences in excitatory
      postsynaptic potential amplitude were observed, with slices from males having
      larger excitatory postsynaptic potential amplitudes than those from females.
      Gonadectomy significantly decreased excitatory postsynaptic potential amplitude
      in slices from male rats. Slices from gonadectomized male and female rats also
      showed a decreased dendritic excitatory postsynaptic potential slope relative to
      slices from intact male and females rats. In vitro application of testosterone
      significantly increased excitatory postsynaptic potential amplitudes in slices
      from both orchidectomized males and ovariectomized females and the population
      spike amplitude of slices from ovariectomized females. Following in vitro
      kindling, slices from intact males showed greater spontaneous burst rates than
      slices from intact females, further suggesting an excitatory effect of
      testosterone. These results suggest: (1) a sex difference in the level of
      baseline excitability between slices from intact males and females as measured by
      excitatory postsynaptic potential amplitudes, (2) testosterone has excitatory
      effects on baseline physiology and kindled hippocampal responses, and (3) slices
      from males show a greater level of excitability than those from females in the in
      vitro kindling model.

PMID- 11823064
TI  - The phosphoinositide 3-kinase and p70 S6 kinase regulate long-term potentiation
      in hippocampal neurons.
AB  - The mechanisms by which long-term changes in synaptic efficacy (e.g., long-term
      potentiation) are maintained are not well understood. There is evidence that
      reorganization of the neuronal actin cytoskeleton is important for consolidation
      of long-term potentiation. In non-neuronal cells, phosphoinositide 3-kinase and
      p70 S6 kinase have been shown to regulate actin polymerization. We have
      investigated the subcellular localization of these enzymes in cultured
      hippocampal pyramidal neurons and their possible role in hippocampal long-term
      potentiation. Immunohistochemical analysis revealed enrichment of both enzymes in
      the growth cones and filopodia of extending neurites, whereas p70 S6 kinase was
      also present at the soma. Antibodies to the phosphorylated form of p70 S6 kinase
      confirmed its activity in these locations. Interestingly, both enzymes displayed
      strong colocalization with F-actin in discrete regions of developing neurites. In
      hippocampal slices, the maintenance of long-term potentiation was attenuated by
      either rapamycin or 2-(4-morpholinyl)-8-phenyl-1(4H)-1-benzopyran-4-one,
      inhibitors of p70 S6 kinase and phosphoinositide 3-kinase, respectively. Our
      findings provide evidence for a novel biochemical pathway involving
      phosphoinositide 3-kinase and p70 S6 kinase that is important for the maintenance
      of hippocampal long-term potentiation, possibly via regulation of actin dynamics.

PMID- 11823065
TI  - Combined neurotrophic supplementation and caspase inhibition enhances survival of
      fetal hippocampal CA3 cell grafts in lesioned CA3 region of the aging
      hippocampus.
AB  - Fetal hippocampal CA3 cells show excellent survival when homotopically grafted
      into the kainic acid-lesioned CA3 region of the young adult hippocampus, a model
      of temporal lobe epilepsy. However, survival of these cells in the kainic acid
      lesioned CA3 region of the aging hippocampus is unknown. We hypothesize that
      fetal CA3 grafts into the lesioned CA3 region of the middle-aged and aged
      hippocampus exhibit significantly diminished cell survival compared with similar
      grafts in the lesioned young adult hippocampus unless pre-treated and
      transplanted with factors that augment graft cell survival. We analyzed cell
      survival of 5'-bromodeoxyuridine-labeled embryonic day 19 CA3 grafts following
      their transplantation into the lesioned CA3 region of the middle-aged and aged
      rat hippocampus. Grafts were placed 4 days after an i.c.v. administration of
      kainic acid, and absolute cell survival of grafts was quantified 1 month after
      grafting using 5'-bromodeoxyuridine immunostaining of serial sections and the
      optical fractionator counting method. Grafts into both middle-aged and aged
      hippocampus exhibited analogous but significantly diminished cell survival (30%
      of injected cells) compared with similar grafts into the young adult hippocampus
      (72% cell survival). However, the extent of cell survival of CA3 grafts pre
      treated and transplanted with a combination of neurotrophic factors brain-derived
      neurotrophic factor and neurotrophin-3 and the caspase inhibitor acetyl-tyrosinyl
      valyl-alanyl-aspartyl-chloro-methylketone was significantly enhanced in both
      middle-aged and aged hippocampus (51-63% cell survival). These results underscore
      that aging impairs the conduciveness of the CA3 region for robust survival of
      homotopic fetal CA3 grafts after lesion. However, a combined neurotrophic
      supplementation and caspase inhibition significantly enhances survival of fetal
      CA3 cells in the lesioned aging hippocampus. Thus, pre-treatment and grafting of
      donor cells with a combination of factors that support growth of specific donor
      cells may considerably enhance survival and integration of fetal grafts into the
      lesioned aging CNS in clinical trials.

PMID- 11823066
TI  - Somatostatin modulates Ca2+ currents in neostriatal neurons.
AB  - Somatostatin is synthesized and released by aspiny interneurons of the
      neostriatum. This work investigates the actions of somatostatin on rat
      neostriatal neurons of medium size (ca. 6 pF). Somatostatin (1 microM) reduces
      both calcium action potentials (20 mM tetraethylammonium) by ca. 24% and calcium
      currents by ca. 35%, in all cells tested. This action was produced in the
      presence of tetrodotoxin and in dissociated cells and was blocked by cyclo(-7
      aminoheptanoyl-phe-d-try-lys-O-benzyl-thr) acetate (CPP-1), a somatostatin
      receptor antagonist. Except for nitrendipine (5 microM), several calcium channel
      antagonists, 1 microM omega-conotoxin GVIA, 400 nM omega-agatoxin TK, and 1
      microM omega-conotoxin MVIIC, partially occluded somatostatin action. According
      to the calcium channel types known to be blocked by these antagonists, P/Q-type
      channels appeared to be the channels mainly modulated by somatostatin, followed
      by N-type channels. Since these channel types generate the afterhyperpolarizing
      potential in spiny neurons, we investigated the action of somatostatin on this
      event. Somatostatin reduces the amplitude of the afterhyperpolarizing potential
      by ca. 39%. This action is occluded by omega-agatoxin TK and omega-conotoxin
      MVIIC but not by omega-conotoxin GVIA or nicardipine. Thus, the action of
      somatostatin on the afterhyperpolarizing potential is mainly mediated by P/Q-type
      calcium channels. The block of the slow afterhyperpolarizing potential made most
      neurons exhibit an irregular firing mode, suggesting that ion currents other than
      calcium may also be affected by somatostatin. We conclude that somatostatin
      exerts a direct postsynaptic effect on neostriatal neurons via the activation of
      somatostatin receptors. This action affects non-L-type calcium channels and
      therefore modifies the afterhyperpolarizing potential and the firing pattern. It
      is proposed that somatostatin and its analogues may have profound effects on the
      motor functions controlled by the basal ganglia.

PMID- 11823067
TI  - Comparative study of the neuroprotective effect of dehydroepiandrosterone and
      17beta-estradiol against 1-methyl-4-phenylpyridium toxicity on rat striatum.
AB  - The effects of dehydroepiandrosterone, estradiol and testosterone on 1-methyl-4
      phenylpyridium (MPP+)-induced neurotoxicity of the nigrostriatal dopaminergic
      system were examined in rat. They were subjected to a unilateral intrastriatal
      infusion of the following treatment conditions: MPP+ alone or co-injection of
      MPP+ plus each hormone. Four days after injection, concentrations of dopamine and
      their metabolites were determined from the corpus striatum. To corroborate the
      neurochemical data an immunohistochemical analysis of tyrosine hydroxylase
      immunoreactive fibers and acetylcholinesterase histochemistry in the striatum was
      performed. Moreover, we performed a dose-response study of the three hormones on
      the high-affinity dopamine transport system in rat striatal synaptosomes. Rats co
      injected within the striatum with MPP+ and either dehydroepiandrosterone or
      estradiol had significantly greater concentrations of dopamine and less tyrosine
      hydroxylase-immunoreactive fibers and acetylcholinesterase fiber density loss
      compared with their respective controls. In addition, 4 days after injection, the
      brain was fixed and cut into coronal sections, and was immunostained with major
      histocompatibility complex class II antigens for activated microglia, and glial
      fibrillary acidic protein for activated astrocytes. Dehydroepiandrosterone also
      attenuated microglial cell activation. In contrast, testosterone showed
      reductions in dopamine concentrations similar to those obtained by MPP+. The
      protective effect of dehydroepiandrosterone against the MPP+ neurotoxic
      dopaminergic system may be produced by its partial prevention of MPP+ inhibition
      of NADH oxidase activity, whereas the estradiol may function as a neuroprotectant
      by reducing the uptake of MPP+ into dopaminergic neurons. Our findings we suggest
      indicate that dehydroepiandrosterone and estradiol by a non-genomic effect may
      have an important modulatory action, capable of attenuating degeneration within
      the striatum, and in this way serve as neuroprotectants of the nigrostriatal
      dopaminergic system.

PMID- 11823068
TI  - In vivo modulation of ventral tegmental area dopamine and glutamate efflux by
      local GABA(B) receptors is altered after repeated amphetamine treatment.
AB  - The activity of dopamine neurons in the ventral tegmental area is modulated by
      excitatory (glutamatergic) and inhibitory (GABAergic) afferents. GABA, released
      by intrinsic neurons and by projection neurons originating in the nucleus
      accumbens and other regions, inhibits dopamine neurons via activation of GABA(A)
      and GABA(B) receptor subtypes. Using in vivo microdialysis in freely moving rats,
      we investigated the role of ventral tegmental area GABA(B) receptors in
      modulating levels of dopamine and glutamate within the ventral tegmental area,
      both in naive rats and in rats treated repeatedly with saline or amphetamine (5
      mg/kg i.p., for 5 days). In naive rats, administration of a potent and selective
      GABA(B) receptor antagonist (CGP 55845A) into the ventral tegmental area elicited
      a concentration-dependent increase in dopamine levels, but did not alter
      glutamate levels. In rats tested 3 days after discontinuing repeated amphetamine
      administration, 50 microM CGP 55845A increased dopamine levels to a greater
      extent than in saline controls. This difference was no longer present in rats
      tested 10-14 days after discontinuing repeated amphetamine injections. CGP 55845A
      (50 microM) had no effect on glutamate levels in the ventral tegmental area of
      saline-treated rats. However, it produced a robust increase in glutamate levels
      in rats tested 3 days, but not 10-14 days, after discontinuing repeated
      amphetamine injections. These results suggest that somatodendritic dopamine
      release is normally under strong tonic inhibitory control by GABA(B) receptors.
      Repeated amphetamine administration enhances GABA(B) receptor transmission in the
      ventral tegmental area during the early withdrawal period, increasing inhibitory
      tone on both dopamine and glutamate levels. This is the first demonstration, in
      an intact animal, that drugs of abuse alter GABA(B) receptor transmission in the
      ventral tegmental area.

PMID- 11823069
TI  - Covariant maturation of nocifensive oral behaviour and c-fos expression in rat
      superior colliculus.
AB  - Injections of formalin into the rodent paw elicit a rapid orientation of the head
      and mouth to the source of discomfort, followed by licking and biting the
      injected area. Previous work has shown this response is dependent on the
      integrity of the midbrain superior colliculus. The present experiments were
      initiated to examine the ontogeny of this oral nocifensive reaction and to
      determine whether it is correlated with the functional maturation of collicular
      responses to noxious stimuli (as indicated by c-fos immunohistochemistry). Rat
      pups at various postnatal ages received formalin injections in either the hindpaw
      or perioral regions. Behaviour was videotaped, and after 120 min, animals were
      killed and the brain and spinal cord processed for Fos-like immunoreactivity.
      Uninjected controls were treated identically. Formalin-induced oral responses
      following injections into the hindpaw and the expression of Fos in the superior
      colliculus were virtually absent until 10 days postnatal, despite the presence of
      Fos-like immunoreactivity in many other structures (e.g. spinal cord,
      parabrachial area, periaqueductal grey). In contrast, animals from day 1 were
      able to use limbs to localise the perioral injection site. From day 10 onward,
      there was a progressive increase in oral nocifensive behaviours and Fos
      expression in the superior colliculus. Our observations are consistent with the
      hypothesis that the normal elaboration of pain-induced oral behaviour is
      initiated only after a functionally active superior colliculus has developed, and
      support previous observations that link the colliculus particularly with oral
      nocifensive behaviours.

PMID- 11823070
TI  - Chronic substance P (NK1) receptor antagonist and conventional antidepressant
      treatment increases burst firing of monoamine neurones in the locus coeruleus.
AB  - The mechanism of action of conventional antidepressants (e.g. imipramine) has
      been linked to modulation of central monoamine systems. Substance P (NK1)
      receptor antagonists may have antidepressant and anxiolytic effects in patients
      with major depressive disorder and high anxiety but, unlike conventional
      antidepressants, are independent of activity at monoamine reuptake sites,
      transporters, receptors, or monoamine oxidase. To investigate the possibility
      that substance P receptor antagonists influence central monoamine systems
      indirectly, we have compared the effects of chronic administration of imipramine
      with that of the substance P receptor antagonist L-760735 on the spontaneous
      firing activity of locus coeruleus neurones. Electrophysiological recordings were
      made from brain slices prepared from guinea-pigs that had been dosed orally every
      day for 4 weeks with either L-760735 (3 mg/kg), imipramine (10 mg/kg), or vehicle
      (water), or naive animals. Chronic, but not acute, treatment with the substance P
      receptor antagonist L-760735, induced burst firing of neurones in the locus
      coeruleus. This effect resembles that of the conventional antidepressant
      imipramine. However, their effects are dissociable since, in contrast to chronic
      imipramine treatment, chronic L-760735 treatment does not cause functional
      desensitisation of somatic alpha2 adrenoceptors. The mechanism by which chronic
      substance P receptor antagonist or conventional antidepressant treatment
      influences the pattern of firing activity of norepinephrine neurones remains to
      be elucidated. However, an indirect action in the periphery or distant brain
      nuclei has been excluded by the use of the in vitro slice preparation, suggesting
      a local site of action in the locus coeruleus.

PMID- 11823071
TI  - Mu- and delta-opioid receptor mRNAs are expressed in periaqueductal gray neurons
      projecting to the rostral ventromedial medulla.
AB  - Opioid antinociception appears to be mediated at least in part by a pathway that
      projects from the periaqueductal gray (PAG) to the rostral ventromedial medulla
      (RVM), but the relationship between opioid receptors and PAG-RVM projection
      neurons is unclear. Previous electrophysiological studies have suggested that
      opioids act directly on some PAG neurons projecting to the RVM. However,
      immunoreactivity for neither the cloned mu-opioid receptor (MOR1) nor the cloned
      delta-opioid receptor (DOR1) has been observed in PAG cells retrogradely labeled
      from the RVM. In the present study, we examined the expression of DOR1 and MOR1
      mRNAs in PAG neurons projecting to RVM using quantitative in situ hybridization
      and retrograde tract-tracing. Mesencephalic neurons were labeled in three male
      Sprague-Dawley rats by microinjection of Fluoro-Gold into the RVM. Five
      micrometer cryostat sections were cut and in situ hybridization was performed
      using full-length cRNA probes labeled with 35S-UTP. Retrogradely labeled neurons
      that were also labeled for MOR1 or DOR1 mRNA were observed in the dorsomedial,
      lateral, and ventrolateral portions of the PAG. Quantification was performed in
      the dorsomedial and ventrolateral PAG using the physical disector. We found that
      of 219 retrogradely labeled neurons, 50 +/- 14% expressed DOR1 mRNA. In a second
      set of 120 Fluoro-Gold-labeled neurons, 27 +/- 8% expressed MOR1 mRNA.
      Significantly more PAG-RVM projection neurons were labeled for MOR1 mRNA in the
      ventrolateral subregion of the PAG than in the dorsomedial subregion. However, no
      significant difference was observed in the proportions of retrogradely labeled
      neurons labeled for DOR1 mRNA in the ventrolateral subregion compared to the
      dorsomedial subregion. We conclude that opioids are likely to exert direct
      effects on PAG-RVM projection neurons through both delta- and mu-opioid
      receptors. In addition, direct effects on PAG-RVM projection neurons from
      activation of MOR1 appear more likely to be exerted in the ventrolateral PAG than
      in the dorsomedial PAG.

PMID- 11823072
TI  - Reduced redox state allows prolonged survival of axotomized neonatal retinal
      ganglion cells.
AB  - Axonal injury to CNS neurons results in apoptotic cell death. The processes by
      which axotomy signals apoptosis are diverse, and may include deprivation of
      target-derived factors, induction of injury factors, bursts of reactive oxygen
      species (ROS), and other mechanisms. Our previous studies demonstrated that death
      of a dissociated retinal ganglion cell, an identified CNS neuron, is ROS
      dependent. To better define the mechanisms by which ROS induce retinal ganglion
      cell death after axotomy, we studied their effects in dissociated neonatal rat
      retinal cultures. Postnatal day 2-4 Long-Evans rat retinal ganglion cells were
      retrogradely labeled with the fluorescent tracer 1,1'-dioctadecyl-3,3,3',3'
      tetramethylindocarbocyanine (DiI). Postnatal day 7-9 retinas were dissociated and
      cultured in the presence of specific ROS generating systems, scavengers, or redox
      modulators. Retinal ganglion cells were identified by DiI positivity and
      viability determined by metabolism of calcein-acetoxymethyl ester. We found that
      ROS scavengers protected against retinal ganglion cell death after acute
      dissociation, and the effects of ROS appeared to be due to shifts in the redox
      potential, as retinal ganglion cell survival was critically dependent on redox
      state, with greatest survival under mildly reducing conditions. Culture of
      retinal ganglion cell with the non-thiol-containing reducing agent
      tris(carboxyethyl)phosphine resulted in long-term survival equivalent to or
      better than with neurotrophic factors. Our data suggest that axotomy-associated
      neuronal death induced by acute dissociation may be partly dependent on ROS
      production, acting to shift the redox state and oxidize one or more key thiols.
      Understanding the mechanisms by which ROS signal neuronal death could result in
      strategies for increasing their long-term survival after axonal injury.

PMID- 11823074
TI  - Initial experience with hyperoxemic reperfusion after primary angioplasty for
      acute myocardial infarction: results of a pilot study utilizing intracoronary
      aqueous oxygen therapy.
AB  - OBJECTIVES: The purpose of this study was to evaluate the feasibility and safety
      of intracoronary hyperoxemic reperfusion after primary angioplasty for acute
      myocardial infarction (MI). BACKGROUND: Hyperoxemic therapy with aqueous oxygen
      (AO) attenuates reperfusion injury and preserves left ventricular (LV) function
      in experimental models of MI. METHODS: In a multi-center study of patients with
      acute MI undergoing primary angioplasty (PTCA), hyperoxemic blood (pO(2): 600 to
      800 mm Hg) was infused into the infarct-related artery for 60 to 90 min after
      intervention. The primary end points were clinical, electrical and hemodynamic
      stability during hyperoxemic reperfusion and in-hospital major adverse cardiac
      events. Global and regional LV function was evaluated by serial echocardiography
      after PTCA, after AO infusion, at 24 h and at one and three months. RESULTS:
      Twenty-nine patients were enrolled (mean age: 58.9+/-12.6 years). Hyperoxemic
      reperfusion was performed successfully in all cases (mean infusion time: 80.8+/
      18.2 min; mean coronary perfusate pO(2): 631+/-235 mm Hg). There were no adverse
      events during hyperoxemic reperfusion or the in-hospital period. Compared with
      baseline, a significant improvement in global wall motion score index was
      observed at 24 h (1.68+/-0.24 vs. 1.48+/-0.24, p < 0.001) with a trend toward an
      increase in ejection fraction (48.6+/-7.3% vs. 51.8+/-6.8%, p = 0.08).
      Progressive improvement in LV function was observed at one and three months,
      primarily due to recovery of infarct zone function. CONCLUSIONS: Intracoronary
      hyperoxemic reperfusion is safe and well tolerated after primary PTCA. These
      preliminary data support the need for a randomized controlled trial to determine
      if hyperoxemic reperfusion enhances myocardial salvage or improves long-term
      outcome.

PMID- 11823073
TI  - Eptifibatide and low-dose tissue plasminogen activator in acute myocardial
      infarction: the integrilin and low-dose thrombolysis in acute myocardial
      infarction (INTRO AMI) trial.
AB  - OBJECTIVES: This study was designed to test the hypothesis that eptifibatide and
      reduced-dose tissue plasminogen activator (t-PA) will enhance infarct artery
      patency at 60 min in patients with acute myocardial infarction (AMI). BACKGROUND:
      Combination fibrin and platelet lysis improves epicardial and myocardial
      reperfusion in AMI. METHODS: Patients were enrolled in a dose finding (Phase A, n
      = 344) followed by a dose confirmation (Phase B, n = 305) protocol. All patients
      received aspirin and weight-adjusted heparin and underwent angiography at 60 and
      90 min. In Phase A, eptifibatide in a single or double bolus (30 min apart) of
      180, 180/90 or 180/180 microg/kg followed by an infusion of 1.33 or 2.0 microg/kg
      per min was sequentially added to 25 or 50 mg of t-PA. In Phase B, patients were
      randomized to: 1) double-bolus eptifibatide 180/90 (30 min apart) and 1.33
      microg/kg per min infusion with 50 mg t-PA (Group I); 2) 180/90 (10 min apart)
      and 2.0 g/kg per min with 50 mg t-PA (Group II); or 3) full-dose, weight-adjusted
      t-PA (Group III). RESULTS: In Phase A, the best rate of Thrombolysis In
      Myocardial Infarction (TIMI) flow grade 3 was achieved using 180/90/1.33
      microg/kg per min eptifibatide with 50 mg t-PA: 65% and 78% at 60 and 90 min,
      respectively. In Phase B, the incidence of TIMI flow grade 3 at 60 min was 42%,
      56% and 40%, for Groups I through III, respectively (p = 0.04, Group II vs. Group
      III). The median corrected TIMI frame count was 38, 33 and 50, respectively (p =
      0.02). TIMI major bleeding was reported in 8%, 11% and 6%, respectively;
      intracranial hemorrhage occurred in 1%, 3% and 2% of patients (p > 0.5 for both).
      The incidences of death (4%, 5% and 7%), reinfarction or revascularization at 30
      days were similar among the three treatment groups. CONCLUSIONS: In comparison
      with standard t-PA regimen, double-bolus eptifibatide (10 min apart) with a 48-h
      infusion and half-dose t-PA (Group II) is associated with improved quality and
      speed of reperfusion. The safety profile of this therapy is similar to that of
      other combination regimens.

PMID- 11823075
TI  - A randomized comparison of the value of additional stenting after optimal balloon
      angioplasty for long coronary lesions: final results of the additional value of
      NIR stents for treatment of long coronary lesions (ADVANCE) study.
AB  - OBJECTIVES: We sought to investigate the clinical benefit of additional stent
      implantation after achieving an optimal result of balloon angioplasty (BA) in
      long coronary lesions (>20 mm). BACKGROUND: Long coronary lesions are associated
      with increased early complications and late restenosis after BA. Stenting
      improves the early outcome, but stent restenosis is also related to both lesion
      length and stent length. METHODS: A total of 437 patients with a single native
      lesion 20 to 50 mm in length were included and underwent BA, using long balloons
      matched to lesion length and vessel diameter (balloon/artery ratio 1.1) to
      achieve a diameter stenosis (DS) <30% by on-line quantitative coronary
      angiography (QCA). "Bail-out stenting" was performed for flow-limiting
      dissections or >50% DS. Patients in whom an optimal BA result was achieved were
      randomized to additional stenting (using NIR stents) or no stenting. The primary
      end point was freedom from major adverse cardiac events (MACE) at nine months,
      and core laboratory QCA was performed on serial angiograms. RESULTS: Bailout
      stenting was necessary in 149 patients (34%) and was associated with a
      significantly increased risk of peri-procedural infarction (p < 0.02). Among the
      288 randomized patients, the mean lesion length was 27+/-9 mm, and the vessel
      diameter was 2.78+/-0.52 mm. The procedural success rate was 90% for the 143
      patients assigned to BA alone (control group), as compared with 93% in the 145
      patients assigned to additional stenting (stent group), which resulted in a
      superior early minimal lumen diameter (0.54 mm, p < 0.001) and led to reduced
      angiographic restenosis (27% vs. 42%, p = 0.022). Freedom from MACE at nine
      months was 77% in both groups. CONCLUSIONS: A strategy of provisional stenting
      for long coronary lesions led to bailout stenting in one-third of patients, with
      a threefold increase in peri-procedural infarction. Additional stenting yielded a
      lower angiographic restenosis rate, but no reduction in MACE at nine months.

PMID- 11823076
TI  - Vascular morphometric changes after radioactive stent implantation: a dose
      response analysis.
AB  - OBJECTIVES: The goal of this study was to evaluate the dose-dependency of
      morphometric changes in the coronary arterial wall after radioactive stenting.
      BACKGROUND: Radioactive stents have been found to reduce intrastent intimal
      hyperplasia (IIH) but lead to a characteristic type of restenosis occurring
      predominantly at the stent edges. METHODS: Fifteen patients underwent
      intravascular ultrasound (IVUS) examination after implantation of a P-32
      radioactive stent and at the six-month follow-up. The post-stent IVUS
      measurements on seven predefined locations of each lesion were subjected to a
      computer algorithm for the development of dose-volume histograms (DVH). Thus, we
      derived the radiation doses delivered to at least 10% and 90% of the adventitia
      (DV10, DV90). The IIH and vascular remodeling at follow-up were correlated with
      the doses in each segment. RESULTS: The IIH was most pronounced at the stent
      edges and lowest in the stent-body, whereas we detected a significant expansive
      remodeling within the stent body. The delivered doses correlated with a decreased
      IIH (r = 0.52, p < 0.001 for DV10 and r = 0.62, p < 0.001 for DV90) and with
      expansive remodeling (r = 0.48, p = 0.009 for DV10 and r = 0.50, p = 0.006 for
      DV90). A DV10 >90 Gy or a DV90 >15 Gy reduced IIH and induced expansive
      remodeling. Plaque growth was not reduced by radioactive stents. CONCLUSIONS: The
      DVH analysis reveals a dose-dependent increase of external elastic lamina area
      behind radioactive stents, whereas plaque growth is not reduced but inverted into
      an outward direction from the stent. A DV10 >90 Gy or a DV90 >15 Gy results in a
      beneficial long-term outcome after radioactive stenting.

PMID- 11823077
TI  - Ethnic differences in coronary atherosclerosis.
AB  - OBJECTIVES: The study was done to evaluate whether ethnic differences exist in
      the prevalence of coronary artery calcification (CAC), and to determine whether
      differences in calcification correlate with the degree of coronary obstruction.
      BACKGROUND: Electron beam tomography (EBT) can be used to quantitate the amount
      of CAC and assist in prognostication of future cardiac events. It is unclear
      whether ethnic differences in coronary mortality are related to differences in
      the prevalence of coronary obstruction and CAC. METHODS: A total of 782
      symptomatic subjects underwent both EBT and angiography. A 50% luminal narrowing
      defined an angiographic obstruction. RESULTS: We observed substantial ethnic
      differences in prevalence of both CAC and angiographic stenosis. In whites (n =
      453), prevalence of CAC (score >0) was 84%, and significant obstruction on
      angiogram was 71%. Compared with whites, blacks (n = 108) had a significantly
      lower prevalence of CAC (62%, p < 0.001) and angiographic disease (49%, p <
      0.01). Hispanics (n = 177) also had a lower prevalence of CAC (71%, p < 0.001)
      and angiographic obstruction (58%, p < 0.01). Asians (n = 44) were not
      significantly different in regard to CAC (73%, p = 0.06) or angiographic stenosis
      (64%, p = 0.30). These ethnic differences remained after simultaneously
      controlling (by use of multiple logistic regression) for age, gender and cardiac
      risk factors. CONCLUSIONS: As compared with whites, blacks and Hispanics had
      significantly lower prevalence of CAC and obstructive coronary disease. Ethnic
      differences in risk-factor profiles do not explain these differences. This study
      demonstrated that whites have a higher atherosclerotic burden than blacks and
      Hispanics, independent of risk-factor differences among symptomatic patients
      referred for angiography.

PMID- 11823079
TI  - Absolute blood flow and oxygen consumption in stunned myocardium in patients with
      coronary artery disease.
AB  - OBJECTIVES: In patients with coronary artery disease (CAD), we sought to
      demonstrate normal myocardial blood flow (MBF) and myocardial oxygen consumption
      (MMRO(2)) to post-ischemic myocardium that exhibited reversible dysfunction and
      the relation between the severity of the dysfunction and the preceding ischemia.
      BACKGROUND: In animal models of stunning, MBF and MMRO(2) are normal or near
      normal, and the severity of stunning is related to the degree of the preceding
      ischemia. METHODS: Myocardial blood flow and MMRO(2) were measured using positron
      emission tomography and oxygen 15-labelled water (H(2)(15)O) and oxygen 15
      labelled oxygen ((15)O(2)), respectively, in 14 patients with CAD and normal left
      ventricular (LV) function. Global ejection fraction and regional LV systolic
      function (SF) were measured using quantitative echocardiography during and after
      dobutamine-induced ischemia. RESULTS: Ejection fraction and SF were reduced 30
      min after dobutamine (both: p < 0.01) but recovered by 120 min. Myocardial blood
      flow (ml/min per g) to regions with reversible LV dysfunction was normal at
      baseline and during dysfunction (0.88 [0.82 to 0.99] and 1.09 [0.75 to 1.37],
      respectively, p = NS) as was MMRO(2) (ml/min per 100 g) (16.64 [10.16 to 16.18]
      and 11.68 [8.43 to 15.30] respectively, p = NS). Left ventricular dysfunction was
      related to stenosis severity and peak MBF. Regions were divided into those
      subtended by a stenosis of <50%, 50% to 80% and >80% luminal diameter. Systolic
      function 30 min after dobutamine was 93.9% (83.4% to 104.4%) (p = NS), 85.4%
      (80.0% to 90.9%) and 67.4% (56.2% to 78.7%) (both: p < 0.001), respectively. Peak
      MBF was 2.0 (1.71 to 2.31), 1.75 (1.65 to 1.85) (p = 0.01 compared with <50%) and
      1.47 (1.33 to 1.60) (p = 0.03 compared with 50% to 80% and p = 0.002 compared
      with <50%), respectively. CONCLUSIONS: In patients with CAD, dobutamine produces
      prolonged, but reversible, LV dysfunction when MBF is normal, confirming
      stunning. This stunning is related to the severity of the coronary stenosis and
      the reduction in peak MBF. Myocardial oxygen consumption to stunned myocardium is
      normal.

PMID- 11823078
TI  - Acute effects of heparin administration on the ischemic threshold of patients
      with coronary artery disease: evaluation of the protective role of the metabolic
      modulator trimetazidine.
AB  - OBJECTIVES: We sought to assess the effects of heparin and the potential
      protective effects of trimetazidine (TMZ) on exercise performance, plasma nitric
      oxide (NO), endothelin-1 (ET-1) and free fatty acid (FFA) release in patients
      with stable coronary artery disease (CAD). BACKGROUND: Heparin has been shown to
      reduce the ischemic threshold in patients with CAD. Trimetazidine may affect
      myocardial substrate utilization by shifting energy production from FFA to
      glucose oxidation. METHODS: In four consecutive days, nine patients with CAD each
      received one of the following four regimens: 1) one tablet of placebo the evening
      before and at 8 AM and 4 PM on the day of the study, 10 ml of saline in a bolus
      10 min before exercise, followed by an infusion of the same preparation; 2)
      placebo at the same times as in the first regimen, 5,000 IU of heparin 10 min
      before exercise, followed by 1,000 IU/h; 3) 20 mg TMZ at the same times as in the
      first regimen, 5,000 IU of heparin 10 min before exercise, followed by 1,000
      IU/h; or 4) TMZ at the same times as in the first regimen, 10 ml of saline 10 min
      before exercise, followed by an infusion of the same preparation. RESULTS: During
      placebo (test 2), heparin reduced the time to 1-mm ST-segment depression and
      prolonged the recovery time, as compared with the results of test 1. When heparin
      was administered after TMZ (test 3), the time to 1-mm ST-segment depression and
      the recovery time were similar to those recorded during saline (test 1). Finally,
      compared with all study phases, TMZ during saline (test 4) prolonged the time to
      1 mm. No changes in NO release were found, whereas ET-1 was decreased at peak
      exercise and during recovery, when the patients were receiving TMZ (tests 3 and
      4). Free fatty acids increased after heparin, both with placebo and TMZ.
      CONCLUSIONS: In patients with CAD, heparin reduces the ischemic threshold.
      Trimetazidine reduces the effects of heparin, probably by inhibiting FFA
      oxidation and enhancing glucose metabolism. The concomitant novel observation of
      reduced ET-1 release is likely to be also dependent on TMZ-induced improvement of
      endothelial metabolism or reduction of myocardial ischemia.

PMID- 11823080
TI  - The histology of viable and hibernating myocardium in relation to imaging
      characteristics.
AB  - OBJECTIVES: This study characterizes the histology of myocardium predicted to be
      hibernating using three different imaging techniques to explain the discordance
      among them. BACKGROUND: Both radionuclide and functional imaging techniques were
      used to assess myocardial hibernation. The former have high sensitivity and the
      latter high specificity for predicting functional recovery. METHODS: Nineteen
      patients underwent thallium-201 and 99m-technetium tetrofosmin myocardial
      perfusion imaging, and dobutamine magnetic resonance imaging (MRI), prior to
      coronary bypass grafting. Criteria for predicted hibernation for each technique
      were defined before operation. Postoperative criteria for scar and true
      hibernation were also defined. Biopsies were analyzed for myocyte volume fraction
      (MVF), glycogen deposition and pathologic cell features. RESULTS: Thallium was
      most sensitive in predicting hibernation (88%) and MRI most specific (84%); and,
      although there was good agreement between thallium and tetrofosmin (85%),
      agreement between MRI and thallium (59%) or tetrofosmin (59%) was poor. For each
      technique, MVF was higher in segments predicted to be hibernating rather than
      scar (p < 0.05). The MVF was higher where both thallium and MRI predicted
      hibernation (0.77+/-0.07) than in segments predicted by thallium alone (0.69+/
      0.13, p < 0.05). Proven hibernating segments had a higher MVF than scar (0.72+/
      0.11 vs. 0.6+/-0.26, p < 0.05). CONCLUSIONS: Preservation of myocyte fraction is
      an important determinant of functional recovery after revascularization. A higher
      myocyte fraction is required to maintain contractile reserve than to achieve
      significant tracer uptake. This explains the higher sensitivity of radionuclide
      imaging compared with dobutamine MRI in the identification of myocardial
      hibernation.

PMID- 11823081
TI  - Cardiac sympathetic denervation modulates the sympathoexcitatory response to
      acute myocardial ischemia.
AB  - OBJECTIVES: This study was designed to elucidate the influence of cardiac
      sympathetic denervation on the sympathoexcitatory response to acute myocardial
      ischemia during balloon coronary occlusion (BCO) in humans. BACKGROUND:
      Alterations of cardiac sympathetic nerve function could modulate sympathetic
      reflexes originating from the ischemic area. METHODS: In 23 patients with angina
      pectoris, we quantified the baseline cardiac sympathetic denervation of the
      ischemia-related area by iodine-123 metaiodobenzylguanidine ((123)I-MIBG), and
      transient changes in sympathetic activity during BCO by wavelet analysis of RR
      interval variability. RESULTS: Balloon coronary occlusion resulted in a transient
      augmentation of low-frequency (LF: 0.04 to 0.14 Hz) spectral components of RR
      interval variability in 4 of 12 patients with cardiac denervation and in 8 of 11
      patients without denervation (p < 0.01 by the chi-square test). Consequently, the
      increase in LF components was significantly less during BCO in patients with
      cardiac denervation (34%) than in those without denervation (273%) (interaction:
      p < 0.05). In seven patients with severe ischemia provoked by a fall of > or =
      10% in the left ventricular ejection fraction, LF components increased by 506%
      during BCO, regardless of the condition of cardiac denervation. In contrast, in
      patients with mild ischemia provoked by a fall of <10% in the ejection fraction,
      changes of LF components during BCO were significantly less in patients with
      denervation than in those without denervation (84 vs. 344%, p < 0.05).
      CONCLUSIONS: These findings suggest that if the provoked ischemia is not severe,
      cardiac sympathetic denervation could prevent ischemia-induced
      sympathoexcitation.

PMID- 11823082
TI  - Strain rate measurement by doppler echocardiography allows improved assessment of
      myocardial viability inpatients with depressed left ventricular function.
AB  - OBJECTIVES: This study sought to evaluate whether objective assessment of the
      myocardial functional reserve, using strain rate imaging (SRI), allows accurate
      detection of viable myocardium. BACKGROUND: Strain rate imaging is a new
      echocardiographic modality that allows quantitative assessment of segmental
      myocardial contractility. METHODS: In 37 patients (age 58 +/- 9 years) with
      ischemic left ventricular dysfunction, myocardial viability was assessed using
      low-dose (10 microg/kg body weight per min) two-dimensional dobutamine stress
      echocardiography (DSE), tissue Doppler imaging, SRI and (18)F-fluorodeoxyglucose
      ((18)FDG) positron emission tomography (PET). The peak systolic tissue Doppler
      velocity and peak systolic myocardial strain rate were determined at baseline and
      during low-dose dobutamine stress from the apical views. RESULTS: A total of 192
      segments with dyssynergy at rest were classified by (18)FDG PET as viable in 94
      and nonviable in 98. An increase of peak systolic strain rate from rest to
      dobutamine stimulation by more than -0.23 1/s allowed accurate discrimination of
      viable from nonviable myocardium, as determined by (18)FDG PET with a sensitivity
      of 83% and a specificity of 84%. Receiver operating characteristic (ROC) curve
      analysis showed an area under the curve for prediction of nonviable myocardium,
      as determined by (18)FDG PET using SRI, of 0.89 (95% confidence interval [CI]
      0.88 to 0.90), whereas the area under the ROC curve using tissue Doppler imaging
      was 0.63 (95% CI 0.61 to 0.65). CONCLUSIONS: The increase in the peak systolic
      strain rate during low-dose dobutamine stimulation allows accurate discrimination
      between different myocardial viability states. Strain rate imaging is superior to
      two-dimensional DSE and tissue Doppler imaging for the assessment of myocardial
      viability.

PMID- 11823083
TI  - Isolated ventricular noncompaction is associated with coronary microcirculatory
      dysfunction.
AB  - OBJECTIVES: We sought to analyze whether a microcirculatory dysfunction might be
      associated with isolated ventricular noncompaction (IVNC). BACKGROUND: In IVNC,
      which is a cardiomyopathy thus far "unclassified" by the World Health
      Organization, heart failure and sudden cardiac death are common findings, but the
      pathophysiologic mechanisms are unknown. METHODS: In 12 patients with IVNC and 14
      control subjects, quantitative evaluation of regional myocardial perfusion
      (myocardial blood flow [MBF]) and coronary flow reserve (CFR, hyperemic/baseline
      MBF) was performed using positron emission tomography and (13)N-ammonia. The left
      ventricular myocardium was divided into nine segments, and the two-dimensional
      echocardiogram in each patient with IVNC was compared with CFR in each segment.
      Noncompaction was defined as a two-layered structure with excessive
      trabeculation. RESULTS: The CFR in control subjects averaged 4.2+/-0.9, providing
      a cut-off value > or =2.5, but it was 2.1+/-0.8 in patients with IVNC. A
      perfusion scan defect was found in 14 of 24 segments with noncompaction, although
      no defect was found in 76 of 84 normal segments (overall agreement 83%, p <
      0.0001 by the chi-square test). In 16 of 21 segments with noncompaction, a
      decreased CFR was found; but a decreased CFR was also found in 36 of 60 segments
      without noncompaction (p = NS). In 45 of the 57 segments with wall motion
      abnormalities, CFR was decreased, but it was preserved in 17 of the 24 segments
      with normal wall motion (agreement 77%, p < 0.0001). CONCLUSIONS: In patients
      with IVNC, a decreased CFR is not confined to noncompacted segments, but extends
      to most segments with wall motion abnormalities. Thus, coronary microcirculatory
      dysfunction is associated with IVNC.

PMID- 11823084
TI  - Immunohistologic evidence of myocardial disease in apparently healthy relatives
      of patients with dilated cardiomyopathy.
AB  - OBJECTIVES: This study investigated whether apparently healthy relatives of
      patients with idiopathic dilated cardiomyopathy (DCM) who have left ventricular
      enlargement (LVE) have biopsy evidence of underlying myocardial disease.
      BACKGROUND: Left ventricular enlargement with normal systolic function is common
      among asymptomatic relatives of patients with DCM. Although there is
      circumstantial evidence to suggest that LVE may be a marker of early DCM, its
      pathophysiologic significance remains uncertain. METHODS: Over six years, 767
      asymptomatic relatives of 183 consecutive patients with DCM were evaluated: 37
      (5%) had DCM and 104 (14%) had LVE (left ventricular end-diastolic dimension
      >112% predicted) with normal systolic function. Right ventricular biopsy was
      performed in 32 relatives with LVE, 14 patients with symptomatic DCM and 6
      control subjects with normal ventricular function undergoing elective coronary
      artery bypass graft surgery. Histologic and immunohistochemical analyses,
      including quantitative double immunofluorescence, were performed for leukocyte
      markers (CD3 and CD68), intercellular adhesion molecule-1 (ICAM-1) and human
      leukocyte antigen class II antigens (DR and DQ). RESULTS: Histologic findings
      consistent with DCM were present in 50% of the patients with DCM, 25% of the
      relatives with LVE and 0% of the control subjects. The median CD3 count was
      2.4/mm(2) in patients with DCM, 4/mm(2) in relatives with LVE and 0 in control
      subjects (p = 0.04). Using a threshold of >7 cells/mm(2), 21% of patients with
      DCM and 25% of relatives with LVE were CD3-positive (p = 0.01). Quantitative
      analysis demonstrated DR expression on 55.8+/-22.8%, 63.5+/-18.8% and 30.9+/
      15.7% of the endothelial surface in patients with DCM, relatives and control
      subjects, respectively (p = 0.003). Corresponding values for ICAM expression were
      35.6+/-15.1%, 36.7+/-14.5% and 17.3+/-7.9% (p = 0.013). When combining
      inflammatory and histologic changes, 28 (86%) of LVE, 14 (100%) of DCM and no
      control biopsies were abnormal (p < 0.001). CONCLUSIONS: Most asymptomatic
      relatives of patients with DCM with LVE have histopathologic and immunopathologic
      findings similar to those of patients with established disease. Clinical
      identification and follow-up of such individuals are warranted to prevent
      presentation with advanced DCM and to enable assessment of interventions aimed at
      attenuating disease progression.

PMID- 11823085
TI  - Angiotensin receptor blockers in heart failure: meta-analysis of randomized
      controlled trials.
AB  - OBJECTIVES: We sought to determine the effect of angiotensin receptor blockers
      (ARBs) on mortality and hospitalization in patients with heart failure (HF).
      BACKGROUND: There is uncertainty regarding the efficacy of ARBs as substitute or
      adjunctive therapy to angiotensin-converting enzyme inhibitors (ACEIs) in the
      treatment of HF. METHODS: We conducted a meta-analysis of all randomized
      controlled trials that compared ARBs with either placebo or ACEIs in patients
      with symptomatic HF. The pooled outcomes were all-cause mortality and
      hospitalization for HF. RESULTS: Seventeen trials involving 12,469 patients were
      included. Overall, ARBs were not superior to controls in the pooled rates of
      death (odds ratio: 0.96; 95% confidence interval: 0.75 to 1.23) or
      hospitalization (0.86; 0.69 to 1.06). Stratified analysis, however, showed a non
      significant trend in benefit of ARBs over placebo in reducing mortality (0.68;
      0.38 to 1.22) and hospitalization (0.67; 0.29 to 1.51) when given in the absence
      of background ACEI therapy. When compared directly with ACEIs, ARBs were not
      superior in reducing either mortality (1.09; 0.92 to 1.29) or hospitalization
      (0.95; 0.80 to 1.13). In contrast, the combination therapy of ARBs and ACEIs was
      superior to ACEIs alone in reducing hospitalization (0.74; 0.64 to 0.86) but not
      mortality (1.04; 0.91 to 1.20). CONCLUSIONS: This meta-analysis cannot confirm
      that ARBs are superior in reducing all-cause mortality or HF hospitalization in
      patients with symptomatic HF, particularly when compared with ACEIs. However, the
      use of ARBs as monotherapy in the absence of ACEIs or as combination therapy with
      ACEIs appears promising.

PMID- 11823086
TI  - A randomized trial of the efficacy of multidisciplinary care in heart failure
      outpatients at high risk of hospital readmission.
AB  - OBJECTIVES: We sought to determine whether a multidisciplinary outpatient
      management program decreases chronic heart failure (CHF) hospital readmissions
      and mortality over a six-month period. BACKGROUND: Hospital admission for CHF is
      an important problem amenable to improved outpatient management. METHODS: Two
      hundred patients hospitalized with CHF at increased risk of hospital readmission
      were randomized to a multidisciplinary program or usual care. A study
      cardiologist and a CHF nurse evaluated each patient and made recommendations to
      the patient's primary physician before randomization. The intervention team
      consisted of a cardiologist, a CHF nurse, a telephone nurse coordinator and the
      patient's primary physician. Contact with the patient was on a prespecified
      schedule. The CHF nurse followed an algorithm to adjust medications. Patients in
      the nonintervention group were followed as usual. The primary outcome was the
      composite of the number of CHF hospital admissions and deaths over six months,
      compared by using a log transformation t test by intention-to-treat analysis.
      RESULTS: The median age of the study patients was 63.5 years, and 39.5% were
      women. There were 43 CHF hospital admissions and 7 deaths in the intervention
      group, as compared with 59 CHF hospital admissions and 13 deaths in the
      nonintervention group (p = 0.09). The quality-of-life score, percentage of
      patients on target vasodilator therapy and percentage of patients compliant with
      diet recommendations were significantly better in the intervention group. Cost
      per patient, in 1998 U.S. dollars, was similar in both groups. CONCLUSIONS: This
      study demonstrates that a six-month, multidisciplinary approach to CHF management
      can improve important clinical outcomes at a similar cost in recently
      hospitalized high-risk patients with CHF.

PMID- 11823087
TI  - Apoptotic pathway activation from mitochondria and death receptors without
      caspase-3 cleavage in failing human myocardium: fragile balance of myocyte
      survival?
AB  - OBJECTIVES: Activation of the caspase cascade through the mitochondrial and/or
      death receptor pathway was investigated in the failing human myocardium, in which
      the mode and extent of the cascade activation are unknown. BACKGROUND: In
      terminal heart failure, a loss of cardiomyocytes by overload-induced apoptosis is
      an attractive mechanism, explaining the progressive character of the disease.
      However, its relevance is unclear, because the specificity of probes for
      apoptotic deoxyribonucleic acid damage is under debate. METHODS: Left ventricular
      specimens from 36 explanted failing and 21 nonfailing donor hearts were used for
      messenger ribonucleic acid detection by semiquantitative reverse-transcription
      polymerase chain reaction. From these groups, immunoblot analysis was performed
      in samples from nine failing and six nonfailing donor hearts. RESULTS: In
      terminally failing hearts, there was a significant accumulation of cytochrome c
      in the cytosol, which was associated with activation of caspase-9 and
      downregulation of its inhibitor, caspase-9S. Similarly, the death receptor
      induced pathway revealed activation of caspase-8, combined with downregulation of
      its inhibitors, flice-like inhibitory protein-L (FLIP(L)) and FLIP(S). The
      unspecific caspase inhibitors, XIAP, hIAP-1 and hIAP-2, were also downregulated.
      However, the terminal effector caspase-3 was not activated, and its substrate
      gelsolin, acting in its uncleaved form as a feedback inhibitor of caspase-3, was
      not cleaved. CONCLUSIONS: In the terminally failing human myocardium, the caspase
      cascade is partially activated in the presence of a consistent phenotype shift
      toward enhanced susceptibility to apoptosis. Although the system is still under a
      fragile control, the partial initiation of the apoptotic program may be of
      functional relevance also for the surviving cardiomyocytes.

PMID- 11823088
TI  - Doppler myocardial imaging to evaluate the effectiveness of pacing sites in
      patients receiving biventricular pacing.
AB  - OBJECTIVES: The goal of this study was to compare the efficacy of biventricular
      pacing (BIV) at the most delayed wall of the left ventricle (LV) and at other LV
      walls. BACKGROUND: Biventricular pacing could provide additional benefit when it
      is applied at the most delayed site. METHODS: In 31 patients with advanced
      nonischemic heart failure, the activation delay was defined, in blind before BIV,
      by regional noninvasive Tissue Doppler Imaging as the time interval between the
      end of the A-wave (C point) and the beginning of the E-wave (O point) from the
      basal level of each wall. The left pacing site was considered concordant with the
      most delayed site when the lead was inserted at the wall with the greatest
      regional interval between C and O points (CO(R)). After BIV, patients were
      divided into group A (13/31) (i.e., paced at the most delayed site) and group B
      (18/31) (i.e., paced at any other site). RESULTS: After BIV, in all patients LV
      end-diastolic (LVEDV) and end-systolic (LVESV) volumes decreased (p = 0.025 and
      0.001), LV ejection fraction (LVEF) increased (p = 0.002), QRS narrowed (p =
      0.000), New York Heart Association class decreased (p = 0.006), 6-min walked
      distance (WD) increased (p = 0.046), the interval between closure and opening of
      mitral valve (CO) and isovolumic contraction time (ICT) decreased (p = 0.001 and
      0.000), diastolic time (EA) and Q-P(2) interval increased (p = 0.003 and 0.000),
      while Q-A(2) interval and mean performance index (MPI) did not change. Group A
      showed greater improvement over group B in LVESV (p = 0.04), LVEF (p = 0.04),
      bicycle stress testing work (p = 0.03) and time (p = 0.08) capacity, CO (p =
      0.04) and ICT (p = 0.02). CONCLUSIONS: After BIV, LV performance improved
      significantly in all patients; however, the greatest improvement was found in
      patients paced at the most delayed site.

PMID- 11823089
TI  - Repetitive monomorphic ventricular tachycardia originating from the aortic sinus
      cusp: electrocardiographic characterization for guiding catheter ablation.
AB  - OBJECTIVES: We sought to investigate the electrocardiographic (ECG)
      characteristics for guiding catheter ablation in patients with repetitive
      monomorphic ventricular tachycardia (RMVT) originating from the aortic sinus cusp
      (ASC). BACKGROUND: Repetitive monomorphic ventricular tachycardia can originate
      from the right ventricular outflow tract (RVOT) and ASC in patients with a left
      bundle branch block (LBBB) morphology and an inferior axis. METHODS: Activation
      mapping and ECG analysis was performed in 15 patients with RMVT or ventricular
      premature contractions. The left main coronary artery (LMCA) was cannulated as a
      marker and for protection during radiofrequency delivery if RMVT originated from
      the left coronary ASC. RESULTS: During arrhythmia, the earliest ventricular
      activation was recorded from the superior septal RVOT in eight patients (group 1)
      and from the ASC in the remaining seven patients (group 2). The indexes of R-wave
      duration and R/S-wave amplitude were significantly lower in group 1 than in group
      2 (31.8+/-13.5% vs. 58.3+/-12.1% and 14.9+/-9.9% vs. 56.7+/-29.5%, respectively;
      p < 0.01), despite similar QRS morphology. In five patients from group 2, RMVT
      originated from the left ASC, with a mean distance of 12.2+/-3.2 mm (range 7.3 to
      16.1) below the ostium of the LMCA. In the remaining two patients, the RMVT
      origin was in the right ASC. All arrhythmias were successfully abolished. None of
      the patients had recurrence or complications during 9+/-3 months of follow-up.
      CONCLUSIONS: On the surface ECG, RMVT from the ASC has a QRS morphology similar
      to that of RVOT arrhythmias. The indexes of R-wave duration and R/S-wave
      amplitude can be used to differentiate between the two origins. Radiofrequency
      ablation can be safely performed within the left ASC with a catheter cannulating
      the LMCA.

PMID- 11823090
TI  - Intracardiac phased-array imaging: methods and initial clinical experience with
      high resolution, under blood visualization: initial experience with intracardiac
      phased-array ultrasound.
AB  - OBJECTIVES: This study was designed to test the feasibility of high-resolution
      phased-array intracardiac imaging. BACKGROUND: Intracardiac echocardiographic
      imaging of the heart during interventional electrophysiologic (EP) procedures has
      been limited by inadequate ultrasound penetration and absence of Doppler
      hemodynamic and flow information produced by rotating mechanical ultrasound
      elements. METHODS: A 10F (3.2 mm) phased-array, variable 5.5 to 10 MHz frequency
      imaging catheter with a four-way deflectable tip was applied in 24 patients
      undergoing EP studies. Sixteen prespecified cardiac targets were imaged from a
      right heart venue. RESULTS: Fifteen patients had no underlying organic heart
      disease; nine had ischemic, cardiomyopathic, valvular or congenital heart
      disorders. Longitudinal and short-axis imaging readily disclosed each cardiac
      valve, support structures and chamber, as well as the pericardium, right and left
      atrial appendages, the junction of the right atrium and superior vena cava,
      crista terminalis, tricuspid valve isthmus, coronary sinus orifice, membranous
      fossa ovalis and pulmonary veins. The average target depth was 8.8+/-1.5 cm
      (range 0.5 to 15 cm), with adequate penetration at a 7.5 MHz imaging frequency.
      Color flow and Doppler utilities clearly characterized transaortic and pulmonic
      valve and pulmonary vein blood flow, including during low output states.
      CONCLUSIONS: These first human studies with this technology demonstrate the
      methods, feasibility and utility of intracardiac phased-array vector and Doppler
      imaging for long-axis, apex-to-base global cardiac imaging. High resolution of
      endocardial structures and catheters suggests additional utility for visualizing
      interventional procedures from the right heart.

PMID- 11823091
TI  - Flecainide and sotalol: a new combination therapy for refractory supraventricular
      tachycardia in children <1 year of age.
AB  - OBJECTIVES: The goal of this study was to assess the efficacy and safety of the
      combination therapy of flecainide and sotalol for the treatment of refractory
      supraventricular tachycardia (SVT) in children <1 year of age. BACKGROUND:
      Supraventricular tachycardia in infants can be refractory to single-drug as well
      as standard combination medical therapy. Radiofrequency ablation (RFA) is the
      definitive treatment of refractory SVT; however, interventional therapy poses a
      high risk of morbidity and mortality in this age group. METHODS: A retrospective
      review was performed identifying infants who required flecainide and sotalol to
      control refractory SVT. Patient age, previous drug therapy, duration of
      treatment, flecainide levels and corrected QT intervals were recorded; 24 h
      Holter monitoring was utilized to gauge efficacy of treatment. Efficacy was
      defined as suppression of SVT to no more than rare nonsustained episodes or
      slowing of SVT to a clinically tolerable rate. RESULTS: Ten patients (median age:
      29 days, range: 1 to 241 days) failed at least two antiarrhythmic agents
      including either flecainide or sotalol as single agents before initiating
      combination therapy. Efficacy was achieved in all patients. The failure rate for
      therapy was reduced from 100% to 0% (95% confidence interval: 0% to 26%). The
      median doses used were: flecainide 100 mg/m(2)/day (range: 40 to 150 mg/m(2)/day)
      and sotalol 175 mg/m(2)/day (range: 100 to 250 mg/m(2)/day). Median duration of
      therapy was 16 months (range: 5 to 35 months). No proarrhythmia occurred.
      CONCLUSIONS: The combination of flecainide and sotalol can safely and effectively
      control refractory SVT and may obviate the need for RFA in children <1 year.

PMID- 11823092
TI  - Why do cyclo-oxygenase-2 inhibitors cause cardiovascular events?
AB  - This report confirms evidence that selective nonsteroidal anti-inflammatory drugs
      (NSAIDs), such as celecoxib, can lead to thrombotic cardiovascular events.
      Aspirin, a nonselective COX-1 (cyclo-oxygenase) and COX-2 inhibitor may result in
      gastric toxicity. For this reason, selective COX-2 inhibitors have been developed
      to reduce erosion of the gastric mucosa. Both selective and nonselective NSAIDs
      reduce prostacyclin formation in the infarcted heart; they accomplish this by
      tipping the balance of prostacyclin/thromboxane in favor of thromboxane, a
      prothrombotic eicosanoid. The relative increase in thromboxane, coupled with a
      diminution in prostacyclin in infarcted heart muscle, can lead to the development
      of thrombotic cardiovascular events. This may be prevented by the addition of a
      nitric oxide donor to NSAIDs.

PMID- 11823093
TI  - Detection of coronary stenosis and myocardial viability using a single
      intravenous bolus injection of BR14.
AB  - OBJECTIVES: The aim of the study was to determine whether coronary stenosis can
      be detected and myocardial viability assessed after myocardial infarction from a
      single venous bolus injection of BR14, a new ultrasound contrast agent.
      BACKGROUND: BR14 is an ultrasound contrast agent that, like (201)Tl, demonstrates
      redistribution. Whether this principle can be used to determine myocardial
      viability is not known. METHODS: Non-critical (n = 6) or flow-limiting (n = 4)
      stenoses were placed on coronary arteries of 10 open-chest dogs, which then
      underwent 2 h of coronary occlusion followed by reperfusion through the stenosis.
      Hyperemia was induced to create flow mismatch in the dogs with non-critical
      stenosis. Hyperemia was not induced in dogs with reduced resting coronary blood
      flow. All dogs were given 2 ml of BR14 as a bolus injection and serial images
      were obtained. Myocardial blood flow (MBF) was measured using radiolabeled
      microspheres. At the end of the experiment, tissue staining was performed to
      determine infarct size and topography. RESULTS: Initial images demonstrated flow
      mismatch between the normal bed and that subtended by the stenosis (during
      hyperemia in dogs without critical stenosis and during rest in those with reduced
      resting MBF). The perfusion defect size correlated well with radiolabeled
      microsphere-derived hypoperfused zone (r = 0.89). Regions within the hypoperfused
      zone that had not undergone necrosis showed redistribution, whereas the necrotic
      regions showed a persistent defect, the size of which correlated well with
      infarct size (r = 0.80). CONCLUSIONS: Because of its ability to redistribute,
      BR14 can define regions of relative hypoperfusion and also discriminate between
      infarcted and viable tissue within the hypoperfused zone after a single venous
      injection. This property lends itself to assessing myocardial perfusion during
      exercise stress.

PMID- 11823094
TI  - Myocardial and microcirculatory kinetics of BR14, a novel third-generation
      intravenous ultrasound contrast agent.
AB  - OBJECTIVES: This study sought to investigate the myocardial and microvascular
      kinetics of BR14, a novel third-generation ultrasound contrast agent. BACKGROUND:
      BR14 produces persistent myocardial opacification after the administration of a
      single intravenous bolus when the left ventricular cavity contrast has
      considerably diminished. The mechanism of this finding is unknown. METHODS: Nine
      open-chest dogs with non-critical stenosis of a single coronary artery were given
      intravenous bolus injections of BR14 during coronary hyperemia. Time versus
      acoustic intensity (AI) plots were generated from the normal and stenosed beds
      and myocardial blood flow (MBF) was measured with radiolabeled microspheres.
      Intravital microscopy was performed on an exteriorized cremaster muscle in 11
      wild-type mice to study the microvascular kinetics of the agent. RESULTS: At peak
      contrast enhancement, the ratio between AI in the stenosed and normal bed was
      0.44+/-0.23, which was similar to the radiolabeled microsphere-derived MBF ratio
      between the two beds (0.45 +/-0.20). At 400 s after injection, the AI ratio
      between the two beds approximated unity (0.99+/-0.07) despite no changes in MBF,
      indicating redistribution of the agent. The myocardial kinetics of BR14 was best
      characterized by a modified lagged normal density function. Only about 3% of
      administered microbubbles were estimated to be retained in the myocardium.
      Intravital microscopy showed that most of these bubbles were retained only
      transiently (2 to 3 s) within capillaries. CONCLUSIONS: BR14 demonstrates
      redistribution because of transient retention within capillaries. Therefore,
      similar to (201)Tl, it could potentially be used to detect both coronary stenosis
      and myocardial viability after a single injection during stress.

PMID- 11823095
TI  - Life goes on.

PMID- 11823096
TI  - President's page: dollars without the sense.

PMID- 11823097
TI  - ACC/AHA guideline update for perioperative cardiovascular evaluation for
      noncardiac surgery--executive summary: a report of the American College of
      Cardiology/American Heart Association Task Force on Practice Guidelines
      (Committee to Update the 1996 Guidelines on Perioperative Cardiovascular
      Evaluation for Noncardiac Surgery).

PMID- 11823099
TI  - Vasomotor effects and pathophysiologic relevance of F(2)-isoprostane formation in
      vascular diseases.

PMID- 11823100
TI  - Percutaneous revascularization versus beating heart CABG or CABG with
      cardiopulmonary bypass in patients with refractory myocardial ischemia.

PMID- 11823101
TI  - Perpetuation of the myth of the Q-wave versus the non-Q-wave myocardial
      infarction.

PMID- 11823104
TI  - A stent with extent-fiction or prophecy?

PMID- 11823105
TI  - Seizure-induced memory impairment is reduced by choline supplementation before or
      after status epilepticus.
AB  - Prenatal choline supplementation can protect rats against cognitive deficits
      induced by status epilepticus induced by the cholinergic agent pilocarpine [J.
      Neurosci. 20 (2000) 1]. In the present day, we have extended this novel finding
      by investigating the effects of pre- and postnatal choline supplementation in
      memory deficits associated with status epilepticus induced with kainic acid (KA).
      In the first experiment pregnant rats received a normal, choline-supplemented, or
      choline deficient diet starting on the 11th day of gestation and continuing until
      postnatal (P) 7. At P42, rats were given a convulsant dosage of KA. Two weeks
      following the KA-induced status epilepticus rats underwent testing of visual
      spatial memory using the Morris water maze test. Rats receiving supplemental
      choline performed better in the water maze than the deficient and control groups.
      Moreover, the activity of hippocampal choline acetyltransferase was 18% lower in
      the choline deficient animals as compared with the other two groups. In the
      second experiment we administered KA to P35 rats that had been given a normal
      diet. Following the status epilepticus the rats were given a choline-supplemented
      or control diet for 4 weeks and then tested in the water maze. Rats receiving
      choline supplementation performed far better than rats receiving a regular diet.
      This study demonstrates that choline supplementation prior to or following KA
      induced status epilepticus can protect rats from memory deficits induced by
      status epilepticus.

PMID- 11823106
TI  - Autosomal dominant epilepsy with febrile seizures plus with missense mutations of
      the (Na+)-channel alpha 1 subunit gene, SCN1A.
AB  - Evidence that febrile seizures have a strong genetic predisposition has been well
      documented. In families of probands with multiple febrile convulsions, an
      autosomal dominant inheritance with reduced penetrance is suspected. Four
      candidate loci for febrile seizures have been suggested to date; FEB1 on 8q13
      q21, FEB2 on 19p, FEB3 on 2q23-q24, and FEB4 on 5q14-15. A missense mutation was
      identified in the voltage-gated sodium (Na(+))-channel beta 1 subunit gene, SCN1B
      at chromosome 19p13.1 in generalized epilepsy with the febrile seizures plus type
      1 (GEFS+1) family. Several missense mutations of the (Na(+))-channel alpha 1
      subunit (Nav1.1) gene, SCN1A were also identified in GEFS+2 families at
      chromosome 2q23-q24.3. The aim of this report is precisely to describe the
      phenotypes of Japanese patients with novel SCN1A mutations and to reevaluate the
      entity of GEFS+. Four family members over three generations and one isolated
      (phenotypically sporadic) case with SCN1A mutations were clinically investigated.
      The common seizure type in these patients was febrile and afebrile generalized
      tonic-clonic seizures (FS+). In addition to FS+, partial epilepsy phenotypes were
      suspected in all affected family members and electroencephalographically
      confirmed in three patients of two families. GEFS+ is genetically and clinically
      heterogeneous, and associated with generalized epilepsy and partial epilepsy as
      well. The spectrum of GEFS+ should be expanded to include partial epilepsies and
      better to be termed autosomal dominant epilepsy with febrile seizures plus
      (ADEFS+).

PMID- 11823107
TI  - Frequency and age-related variables in interictal psychoses in localization
      related epilepsies.
AB  - PURPOSE: Several studies have described that patients with temporal lobe epilepsy
      (TLE) develop psychoses more frequently than patients with extra-temporal
      localization-related epilepsy (LRE). However, few controlled studies have
      demonstrated an increased susceptibility to psychosis in TLE patients. As one of
      a series of multi-center studies on psychosis in epilepsy, we investigated
      whether the frequency of interictal psychosis differs between types of LRE.
      METHODS: We reviewed some biological characteristics of 197 PE patients with
      interictal psychosis and of 456 LRE patients with no history of psychosis. Type
      of PE was determined as TLE, frontal lobe epilepsy, parietal lobe epilepsy,
      occipital lobe epilepsy, and multi-lobar epilepsy/undifferentiated lobar epilepsy
      by clinical symptoms, EEG findings, and neuroimaging. The frequency of psychosis
      for each type of LRE was compared. Ages at onset of epilepsy and psychosis and
      the time interval between onset of each were also analyzed. RESULTS: There was no
      significant correlation between psychosis and epilepsy type (P=0.211). Age
      related variables also failed to show any significant differences between LRE
      types (age at onset of epilepsy, P=0.369; age at onset of psychosis, P=0.852; the
      time interval, P=0.893). CONCLUSIONS: Patients with LREs as well as with TLE are
      susceptible to interictal psychosis. The mean ages at onset of symptoms and the
      interval between onset of epilepsy and onset of psychosis that we observed
      suggest that patients with LREs, regardless of focus, may share similar processes
      in the development of psychiatric symptoms.

PMID- 11823108
TI  - The role of nitric oxide in anticonvulsant and proconvulsant effects of morphine
      in mice.
AB  - Acute subcutaneous administration of lower doses of morphine (0.5, 1 and 3 mg/kg)
      increase the threshold of seizures induced by pentylenetetrazole (PTZ) in mice,
      whereas higher doses of morphine (15, 30 and 60 mg/kg) have proconvulsant
      effects. The effect of systemic administration of nitric oxide synthase (NOS)
      inhibitors N(G)-nitro-L-arginine methyl ester (L-NAME) and N(G)-nitro-L-arginine
      (L-NNA) and nitric oxide synthase (NOS) L-arginine on biphasic effect of morphine
      was investigated. Acute administration of both L-NAME (1, 3 and 10 mg/kg) and L
      NNA (1 and 10 mg/kg) as well as chronic pretreatment with L-NAME (1 and 10 mg/kg,
      4 days) dose-dependently inhibited both the anticonvulsant and proconvulsant
      effects of morphine (1 and 30 mg/kg, respectively). The inhibition was complete
      for anticonvulsant effect while partial for proconvulsant effect. L-arginine at
      doses that did not affect seizure threshold per se (acute, 30 and 60 mg/kg;
      chronic, 60 mg/kg) potentiated both anticonvulsant and proconvulsant properties
      of less potent doses of morphine (0.5 and 15 mg/kg, respectively). The L-arginine
      induced potentiation of both phases of morphine effect was blocked by L-NAME (0.5
      30 mg/kg). Moreover, low and per se non-effective doses of naloxone (0.1 mg/kg)
      and L-NAME (0.3, 0.5 or 1 mg/kg) showed additive effects in inhibiting both
      phases of morphine effects. These results support the involvement of L
      arginine/nitric oxide pathway in the modulation of seizure threshold by morphine.

PMID- 11823109
TI  - Heightened seizure severity in somatostatin knockout mice.
AB  - Patients and experimental models of temporal lobe epilepsy display loss of
      somatostatinergic neurons in the dentate gyrus. To determine if loss of the
      peptide somatostatin contributes to epileptic seizures we examined kainate-evoked
      seizures and kindling in somatostatin knockout mice. Somatostatin knockout mice
      were not observed to experience spontaneous seizures. Timm staining,
      acetylcholinesterase histochemistry, and immunocytochemistry for NPY, calbindin,
      calretinin, and parvalbumin revealed no compensatory changes or developmental
      abnormalities in the dentate gyrus of somatostatin knockout mice. Optical
      fractionator counting of Nissl-stained hilar neurons showed similar numbers of
      neurons in wild type and somatostatin knockout mice. Mice were treated
      systemically with kainic acid to evoke limbic seizures. Somatostatin knockout
      mice tended to have a shorter average latency to stage 5 seizures, their average
      maximal behavioral seizure score was higher, and they tended to be more likely to
      die than controls. In response to kindling by daily electrical stimulation of the
      perforant path, to more specifically challenge the dentate gyrus, mean
      afterdischarge duration in somatostatin knockout mice was slightly longer, but
      the number of treatments to five stage 4-5 seizures was similar to controls.
      Although we cannot exclude the possibility of undetected compensatory mechanisms
      in somatostatin knockout mice, these findings suggest that somatostatin may be
      mildly anticonvulsant, but its loss alone is unlikely to account for seizures in
      temporal lobe epilepsy.

PMID- 11823110
TI  - Felbamate-induced apoptosis of hematopoietic cells is mediated by redox-sensitive
      and redox-independent pathways.
AB  - Felbamate (FBM; 2-phenyl-1,3-propanediol dicarbamate) is an approved
      antiepileptic drug shown to be effective in a variety of seizure disorders
      refractory to other treatments. However, its use has been restricted because of
      association with occurrence of rare cases of aplastic anemia and hepatic failure.
      Since it was shown that FBM metabolism requires glutathione (GSH), we used two
      experimental protocols to determine if the effects of specific metabolites were
      sensitive to redox pathways. FBM and its metabolite W873 (2-phenyl-1,3
      propanediol monocarbamate), at 0.1 mg/ml, induced increased apoptosis of bone
      marrow cells from B10.AKM mice as compared with B10.BR mice. Study of the effects
      of the drug on human promonocytic cell line U937 cells showed that FBM and the
      metabolite W2986 [2-(4-hydroxyphenyl)-1,3 propanediol dicarbamate], at higher
      concentrations (0.5 mg/ml), induced apoptosis in this cell line. We also observed
      that while FBM and its metabolites induced increased apoptosis of B cells with
      reduced intracellular GSH levels, addition of exogenous GSH decreased apoptosis
      induced by W873 but did not significantly affect apoptosis induced by FBM or
      W2986. Our results suggest that, at concentrations used during the present
      investigations, FBM metabolites induce apoptosis via redox-sensitive and redox
      independent pathways.

PMID- 11823111
TI  - Serum copper, zinc, selenium, glutathione peroxidase and superoxide dismutase
      levels in epileptic children before and after 1 year of sodium valproate and
      carbamazepine therapy.
AB  - To assess whether epileptic children have abnormal values of serum copper (Cu),
      zinc (Zn), selenium (Se), glutathione peroxidase (GSH-PX) and superoxide
      dismutase (CuZn-SOD), and to evaluate the effect of long-term therapy with sodium
      valproate (VPA) and carbamazepine (CBZ) on these parameters, we studied 36
      epileptic patients before the beginning of therapy and after 1 year of therapy
      with VPA or CBZ. Before the beginning of therapy, there were no differences in
      levels of all parameters studied between controls and epileptics. After 1 year of
      therapy, patients treated with VPA and CBZ continued to show normal values. In
      conclusion our study demonstrates that epilepsy per se and treatment with VPA and
      CBZ do not affect levels of Cu, Zn, Se, GSH-PX and CuZn-SOD concentrations.

PMID- 11823112
TI  - Dose-response effect of levetiracetam 1000 and 2000 mg/day in partial epilepsy.
AB  - PURPOSE: To evaluate the efficacy, dose-response, tolerability, and withdrawal
      effects of levetiracetam (Keppra) as adjunctive therapy in adult patients with
      partial epilepsy. METHODS: In this European multicenter, double-blind,
      randomized, cross-over trial, levetiracetam 1000 or 2000 mg/day given in two
      divided doses was compared to placebo as add-on therapy in 324 patients with
      refractory partial seizures with or without secondary generalization. This trial
      consisted of six periods: an 8- or 12-week baseline, a treatment period A (4-week
      titration and 12-week evaluation), a treatment period B (4-week titration and 12
      week evaluation), and a withdrawal period. During each evaluation period (A and
      B), patients received two of the three possible treatment regimens. RESULTS: This
      study provides additional information on dose-response effects and withdrawal
      phenomena and confirms the responder and seizure freedom rates previously
      reported in the parallel part of the study (Epilepsia 41 (2000) 1179-1186). Both
      doses of levetiracetam significantly decreased mean partial seizure frequency
      compared with placebo (P<0.001), and significantly more patients receiving
      levetiracetam had > or = 50 and > or = 75% reductions in partial seizure
      frequency (1000 mg, P=0.004 and P=0.043, respectively; 2000 mg P=0.001 and
      P<0.001, respectively). In addition, 5.5% (10/183) of patients receiving
      levetiracetam 1000 mg/day and 6.3% (11/175) of patients receiving levetiracetam
      2000 mg/day were seizure-free during the corresponding evaluation period,
      compared with 1.2% (2/172) of patients on placebo. A within-patient comparison
      revealed a significantly greater responder rate for the higher levetiracetam dose
      (P=0.018). The most commonly reported adverse effects (> or = 5% and more
      frequent in one of the groups with levetiracetam) were headache, asthenia,
      infection, somnolence, pharyngitis, dizziness, and pain. No withdrawal-related
      adverse events were reported during the cross-titration period. CONCLUSIONS:
      Levetiracetam was effective and well-tolerated and decreased seizure frequency in
      a dose-dependent manner, with no evidence of typical withdrawal-related adverse
      events or rebound phenomena after withdrawal or down-titration.

PMID- 11823113
TI  - Hyperandrogenism, postprandial hyperinsulinism and the risk of PCOS in a cross
      sectional study of women with epilepsy treated with valproate.
AB  - Among a sample of 43 women with epilepsy treated for at least 2 years with
      valproate (n=22) or other antiepileptic drugs (AEDs) (n=21), polycystic ovary
      syndrome (PCOS) was diagnosed in three women, two of them were treated with
      valproate. Although the rate of PCOS and of menstrual disturbances, weight body
      mass index (BMI) and waist to hip ratio as well as fasting blood glucose levels,
      fasting insulin, proinsulin and C-peptide values was similar in this small sample
      of women treated with valproate and other AEDs, valproate exposure was associated
      with higher androgen levels, higher postprandial (pp) insulin and proinsulin
      levels, as well as lower cholesterol and low density lipoprotein (LDL)
      cholesterol levels. The pronounced increase in pp insulin levels during VPA
      treatment may indicate an effect of the fatty acid derivate VPA on pancreatic
      islet cells.

PMID- 11823114
TI  - Semiology of temporal lobe epilepsy in children and adolescents. Value in
      lateralizing the seizure onset zone [corrected].
AB  - PURPOSE: To determine the frequency and lateralizing value of clinical seizure
      symptoms in children and adolescents with drug-resistant temporal lobe epilepsy
      (TLE). METHODS: Patients enrolled had to be <18 years of age and seizure free at
      follow-up for at least 12 months after epilepsy surgery. Patients were assigned
      to two age groups, children (age<12 years) and adolescents (age>12 and <18
      years). Video-tapes were reviewed blinded to patients' demographic data and
      results of additional investigations by two independent raters. Clinical signs of
      known lateralizing significance in adults and additional clinical signs without
      lateralizing value were assessed. RESULTS: 14 patients (eight boys; 2-18 years)
      fulfilled the inclusion criteria. Inter-observer agreement was excellent (kappa
      coefficient: 0.82). Compared with adult series, no differences were found
      concerning overall occurrence of lateralizing signs and lateralizing accuracy.
      There were age-related differences, however, concerning the occurrence of
      individual signs: secondary generalization, complex automatisms and version were
      less frequent in children than in adolescents. CONCLUSIONS: Clinical signs of
      lateralizing value can also be found in children and adolescents, provided that
      the evaluation protocols used consider developmental aspects.

PMID- 11823116
TI  - Occipital sharp waves in idiopathic partial epilepsies--clinical and genetic
      aspects.
AB  - In order to gain new insight into the pathogenesis and nosography of benign
      partial epilepsy with occipital paroxysms (BEOP) we retrospectively analysed
      cases with benign focal sharp waves (SHW) of different localisations, in which
      analogous EEG changes had been found in at least one first degree relative. Fifty
      six families were evaluated. Nineteen cases with occipital SHW (group A) were
      compared with 37 cases without (group B). There was a broad spectrum of
      symptomatology with large overlaps between the two groups. However, a number of
      striking differences, yielding a characteristic picture of early childhood
      epilepsy with occipital foci were identified: (1) Age of onset under 5 years; (2)
      a larger proportion of febrile convulsions (FC 47 vs. 19%); (3) a trend towards a
      higher rate of typical early childhood occipital seizures (26 vs. 5%); (4) a
      higher rate of frontal and generalizing SHW foci (32 vs. 5%; 37 vs. 11%); (5) a
      higher rate of generalized spikes and waves (SW) (46 vs. 14%); (6) a trend
      towards a higher rate of photoparoxysmal response (PPR) (57 vs. 32%). The high
      prevalence of independent genetic traits favours a multifactorial pathogenesis.
      The predisposition to FC with characteristic early seizure onset and varying
      patterns of generalized genetic EEG traits plays a crucial role within the
      complex pathogenetic network. The early-onset benign childhood occipital seizure
      susceptibility syndrome of Panayiotopoulos (Benign Childhood Partial Seizures and
      Related Epileptic Syndromes, John Libbey & Company Ltd., London (1999)) cannot be
      regarded as the sole representative of occipital spikes in early childhood but as
      an important even though rare form of occipital epilepsy.

PMID- 11823115
TI  - A chronic model of atypical absence seizures: studies of developmental and gender
      sensitivity.
AB  - Treatment of Long Evans hooded rats during post-natal brain development with the
      cholesterol synthesis inhibitor, AY-9944 (AY) results in the occurrence of
      atypical absence seizures, which are frequent, recurrent, and life-long. AY
      induced slow spike-and-wave discharges (SSWD) are significantly more frequent and
      prolonged in female Long Evans rats than males. Three groups of experiments were
      performed in order to characterize further the AY model of atypical absence
      seizures, (1) a developmental study was performed to ascertain whether AY-induced
      seizures appear before or after the onset of puberty; (2) male/female differences
      in severity of response to AY was determined in order to answer the question
      whether the gender specificity was a pre- or postpubertal phenomenon; (3) a time
      course study was done to determine the minimum number of postnatal AY doses
      needed to induce the life-long atypical absence seizure state. The data indicate
      that AY-induced atypical absence seizures emerge before the onset of puberty.
      Further, we show that the gender difference in severity of AY-induced seizures
      also is a pre-pubertal phenomenon. Finally, a single dose of AY (7.5 mg/kg)
      administered on post-natal day (P) 5 was sufficient to induce SSWD on the
      electrocorticogram (ECoG). Our results suggest that sex hormones are important in
      the AY model, although the exact role of cholesterol derived steroid hormones in
      the regulation and maintenance of AY induced atypical absence seizures remains to
      be determined.

PMID- 11823117
TI  - Measurement of temporal lobe T2 relaxation times using a routine diagnostic MR
      imaging protocol in epilepsy.
AB  - OBJECTIVE: To determine the applicability of a fast spin-echo (FSE) pulse
      sequence for T2 relaxation time measurements in diagnostic imaging of temporal
      lobe epilepsy (TLE) and in epilepsy research. To compare FSE T2-relaxometry to
      the measurements with multi-echo sequence and visual assessment of MR scans.
      METHODS: MR imaging and T2 relaxometry was performed with widely used 1.5 T
      scanner only. Fast dual-echo sequence (TE-14/85 ms) and multi-echo pulse sequence
      were used for T2 measurements. Normal ranges of T2 values in regions of interest
      in temporal lobe were estimated in 20 healthy controls. Sixty-five patients with
      intractable focal epilepsy were studied. Fifty-five patients had TLE, three
      multilobar focal epilepsy and seven extratemporal focal epilepsy. RESULTS: T2
      measurements with the FSE showed good reproducibility in the test objects and
      control subjects. In one TLE case unilateral focal T2 changes were not identified
      visually. T2-relaxometry was more sensitive than visual inspection of MR scans in
      assessing bilateral hippocampal changes: there were 15 cases with abnormal
      bilateral T2 values. Visually bilateral changes were detected in six out of these
      15 cases (40%). In six cases (40%) only unilateral changes were diagnosed
      visually, and in three cases (20%) bilateral changes were classified as probable
      with qualitative evaluation. T2 relaxation time measurement supplied additional
      objective data in cases with ambiguous hippocampal changes on visual assessment:
      T2-relaxometry confirmed hippocampal abnormalities in seven cases judged visually
      as probable. In four cases with the suspicion of hippocampal changes T2 values
      appeared to be normal. CONCLUSION: In TLE patients, images constructed from FSE
      sequences can be used to estimate T2 relaxation times easily and reliably. T2
      measurements are an objective method to diagnose structural changes in the
      temporal lobe. T2-relaxometry is most helpful to assess bilateral hippocampal
      abnormalities, and thus might have an impact on estimating postsurgical outcome.

PMID- 11823118
TI  - Improved renal clearance and tumor targeting of 99mTc-labeled anti-Tac monoclonal
      antibody Fab by chemical modifications.
AB  - This study was undertaken to improve the renal clearance and tumor targeting
      properties of 99mTc-labeled humanized anti-Tac (HuTac) monoclonal antibody Fab
      fragments using two chemical approaches: 1) labeling with a renal secretion agent
      99mTc-mercaptoacetyltriglycine (MAG3) and 2) lowering its isoelectric point (pI)
      by acylation. HuTac Fab (3.3 mg/mL) was reacted with a trifluorophenyl ester
      (TFP) of 99mTc-MAG3 alone or was additionally reacted with TFP-glycolate to
      reduce the pI. In Balb/c mice, 99mTc-MAG3-Fab (pI > 9.3) rapidly accumulated in
      the kidneys (177% injected dose [ID]/g at 15 min) and then gradually cleared out
      of the kidneys. In contrast, the glycolation (pI 4.6 approximately 6.6)
      drastically reduced the renal uptake (31% ID/g) and also the whole-body retention
      (82% ID vs 101% for the nonglycolated) at 15 min, indicating that the glycolated
      99mTc-MAG3-Fab (pI 4.6 approximately 6.6) was rapidly excreted. The glycolated
      remained in the blood longer than the nonglycolated (1.2% vs 0.3% ID/g at 360
      min), but this effect was less drastic than the effect shown on the renal uptake.
      In nude mice bearing receptor-positive (ATAC4) tumors, the glycolated 99mTc-MAG3
      Fab increased the peak tumor uptake to 14.8% ID/g from 8.3% ID/g for 99mTc-MAG3
      Fab, whereas the glycolation resulted in a drastic reduction of the renal uptake
      at 15 min. We demonstrated that the renal clearance and the tumor targeting of
      Fab could be optimized by chemical modifications.

PMID- 11823119
TI  - Ga-66 labeled somatostatin analogue DOTA-DPhe1-Tyr3-octreotide as a potential
      agent for positron emission tomography imaging and receptor mediated internal
      radiotherapy of somatostatin receptor positive tumors.
AB  - Radionuclide labeled somatostatin analogues selectively target somatostatin
      receptor (SSTR)-expressing tumors as a basis for diagnosis and treatment of these
      tumors. Recently, a DOTA-functionalized somatostatin analogue, DOTATOC (DOTA
      DPhe1-Tyr3-octreotide) has been developed. This compound has been shown to be
      superior to the other somatostatin analogues as indicated by its uniquely high
      tumor-to-non-target tissue ratio. DOTATOC can be labeled with a variety of
      radiometals including gallium radioisotopes. Gallium-66 is a positron emitting
      radionuclide (T(1/2) =9.5 hr; beta+=56%), that can be produced in carrier free
      form by a low-beam energy cyclotron. In this study we investigated SSTR targeting
      characteristics of 66Ga-DOTATOC in AR42J rat pancreas tumor implanted nude mice
      as a potential agent for diagnosis and receptor-mediated internal radiotherapy of
      SSTR-expressing tumors. We compared our results with 67Ga- and 68Ga- labeled
      DOTATOC. The radiolabeling procedure gave labeling yield ranged from 85-95% and
      radiochemical and chemical purity was > 95%. In-vitro competitive binding curves
      and in-vivo competitive displacement studies with an excess of unlabeled peptide
      indicates that there is specific binding of the radioligand to SSTR. Animal
      biodistribution data and serial microPET images demonstrated rapid tumor uptake
      and rapid clearance from the blood and all tissues except kidney. Maximum % ID/g
      values for tumor were 10.0 +/- 0.7, 13.2 +/- 2.1 and 9.8 +/- 1.5 for 66Ga-, 67Ga
      , and 68Ga-DOTATOC, respectively. Calculated tumor, kidney and bone marrow doses
      for 66Ga-DOTATOC based on biodistribution data were 178, 109 and 1.2 cGy/MBq,
      respectively. We conclude that 66Ga labeled DOTATOC can be used for PET diagnosis
      and quantitative imaging-based dosimetry of SSTR positive tumors. 66Ga-DOTATOC
      may also be used in higher doses for ablation of these tumors. However, kidney is
      the critical organ for toxicity (tumor/kidney ratio = 1.64), and high kidney
      uptake must be eliminated before devising a therapy protocol.

PMID- 11823120
TI  - Linkage of boronated polylysine to glycoside moieties of polyclonal antibody;
      boronated antibodies as potential delivery agents for neutron capture therapy.
AB  - Among the ways to deliver comparatively large amounts of boron to cells in vitro
      for boron neutron capture studies is the linkage of a boronated macromolecule
      such as polylysine to an antibody. In order to reduce interference with
      immunoreactivity, boronated polylysine (BPL) was linked to oligosaccharide
      moieties on the IgG molecule distant from the antibody combining sites. The
      resultant bioconjugate was chromatographically separated from free BPL and
      unconjugated antibody using a Sephacryl S300 column. The total measured boron per
      BPL-IgG conjugate, determined by direct current plasma atomic emission
      spectroscopy, was estimated to be approximately 6 x 10(3) atoms. This, together
      with molecular weight estimations, indicated conjugation of about 3 polylysines
      to each IgG molecule. Immunoreactivity of the conjugate was found to be the same
      as that of the unconjugated polyclonal antibody. This was based on its
      concentration dependent interference with immunometric reactions for an antigen
      (TSH), whereas heat inactivated or non-specific antibody had no such inhibitory
      effects. The results support the hypothesis that the binding affinity of the
      conjugate for antigen was preserved after its linkage to BPL under the conditions
      described. The methodology described in this report may have applicability for
      the preparation of boronated antibodies as delivery agents for BNCT.

PMID- 11823121
TI  - Biological investigation of the platinum(II)-[*I]iodohistamine complexes of
      potential synergistic anti-cancer activity.
AB  - Cisplatin chemotherapy in combination with external irradiation or with low-dose
      continuous internal radiotherapy produces significant supra-additive treatment
      effects towards several tumor cells. The purpose of our research is to develop a
      new class of platinum-based anticancer drugs containing moieties of synergistic
      potency such as platinum core and a radiotherapeutic isotope which, delivered
      directly to the tumorous cells by a specifically designed vectors, should produce
      a local enhancement of therapeutic dose. Thus, we have synthesized a new platinum
      iodohistamine complex and its radioactive analogues labeled with I-125 and I-131.
      In the present study some biological properties of those compounds have been
      investigated. The in vitro screening study pointed out that non-radioactive
      platinum-iodohistamine complex possesses high cytostatic activity against COLO
      205 cells, and moderate activity against HL-60 cell line. No cytotoxicity was
      observed against MOLT-4 and L-1210 cells, as well as against VERO normal cells.
      The biodistribution of intravenously administered radioactive platinum-[131I]
      iodohistamine complex to normal rats revealed the highest accumulation in the
      liver (c.a. 40%ID). Intraperitoneal injections of the complex to tumor-bearing
      C3H mice resulted in scattering of the dose in the organs (mainly in GIT, liver,
      kidney). The retention of radioactive complex in neoplastic tissue was 3-4 times
      higher than in normal muscular tissue, although exhibited the tendency to
      decrease with time post injection. The results of the present study show
      promising features of the newly developed platinum-iodohistamine complexes and
      justify prospective investigation of in vivo anticancer potency on animal models
      of solid tumors.

PMID- 11823122
TI  - Scintigraphic imaging using 99mTc-labeled PEG liposomes allows early detection of
      experimental invasive pulmonary aspergillosis in neutropenic rats.
AB  - The value of scintigraphic imaging using 99mTc labeled poly(ethyleneglycol) (PEG)
      -liposomes for detecting invasive pulmonary aspergillosis at different stages of
      the disease was investigated in a rat model. At 24, 48, 72, 120 and 168 h after
      fungal inoculation scintigraphic images were obtained and biodistribution of the
      radiolabel was determined. Findings were compared with serum galactomannan
      detection and other parameters of progression of fungal infection. At 48 h
      liposomal uptake in the infected left lung was increased significantly and 82% of
      the scintigraphic images was assessed positive. Serum galactomannan was only
      detected at 72 h and later. Liposomal uptake in the infected left lung increased
      over time and was significantly correlated with both the size of the pulmonary
      hemorrhagic lesion and the levels of circulating galactomannan. It was concluded
      that scintigraphic imaging using 99mTc-PEG-liposomes allows early detection of
      invasive pulmonary aspergillosis in this model, and that liposomal uptake in the
      infected lung was strongly associated with the severity of the disease.

PMID- 11823123
TI  - Selective in vitro labeling of white blood cells using 99mTc-labeled liposomes.
AB  - We describe a method by which endocytosis-based radiolabeling of WBC is achieved
      using 99mTc-liposomes of optimal size and charge, and of a composition that
      assures both in vitro (whole blood) and intracellular stability of the
      radiopharmaceutical. In our study, excellent in vitro stability of 99mTc
      liposomes with 95% labeling efficiency was observed with >90% stability up to 6 h
      and a minimum of 85% after 24 h of incubation either in normal saline or serum.
      Total WBC labeling efficiency using 99mTc-liposomes determined by radio-thin
      layer chromatographic analysis was 30.6 +/- 2.21%, 20.89 +/- 1.31% for monocytes
      and 9.7 +/- 1.74% for polymorphonuclears. Negligible activity was bound to red
      blood cells. The procedure did not affect the cell viability and the separation
      of the free 99mTc-liposomes from the cells was done by centrifugation.

PMID- 11823125
TI  - Preparation and bioevaluation of 166Ho labelled hydroxyapatite (HA) particles for
      radiosynovectomy.
AB  - The preparation of 166Ho labeled hydroxy apatite (HA) particles for
      radiosynovectomy applications is described in this paper. 166Ho was prepared by
      the irradiation of Ho2O3 at a flux of 1.8 x 10(13) neutrons/cm2/s for about 7
      days. The irradiation resulted in the production of approximately 17 GBq of 166Ho
      activity at the end of six hours post end of bombardment and the corresponding
      specific activity was approximately 3-4 GBq/mg of Ho. The irradiated target was
      dissolved in 0.1 N HCl solution. Radionuclidic purity was ascertained by high
      resolution gamma ray spectrometry. HA particles were synthesized and
      characterized by X-ray diffractometry. Labeling studies were carried out with and
      without citric acid as a transchelating agent. Radiochemical yield and purity of
      the 166Ho-HA particles were ascertained by paper chromatography and by paper
      electrophoresis techniques. Labeling yield of >98% could be achieved at pH 7,
      with 40 mg of HA particles and 8.6 microg of Ho. 166Ho-HA particles prepared were
      stable for 72 h. Bio-evaluation of the 166Ho -HA particles were carried out by
      injecting approximately 74 MBq dose in 200 microL (approximately 8 mg of 166Ho-HA
      particles) directly into the arthritis induced knee joints as well as into the
      healthy knee joints of white New Zealand rabbits. Images of the injected joints
      of the animals recorded using a gamma camera at regular intervals showed good
      retention. Blood samples were collected from the animals and activity assayed in
      a scintillation detector. Experiments were also carried out under identical
      conditions in normal rabbits. In both the cases, it was observed that there was
      no significant extra articular leakage of the injected activity over the study
      period of 96 h post injection.

PMID- 11823124
TI  - Imaging and quantitation of the hypoxic cell fraction of viable tumor in an
      animal model of intracerebral high grade glioma using [18F]fluoromisonidazole
      (FMISO).
AB  - We have demonstrated that FMISO uptake is significantly higher in tumor tissue in
      the C6 intracerebral glioma rat model compared to normal brain, and that there is
      persisting hypoxia in gliomas independent of tumor size. FMISO uptake was
      observed homogeneously throughout viable glioma tissue in tumor sizes ranging
      from 2mm to almost 1cm. Quantitation of uptake of FMISO showed a tumor/brain
      ratio of 1.9 and a tumor/blood ratio of 2.6 at 2 hours post injection.

PMID- 11823126
TI  - Investigations into tumor accumulation and peroxisome proliferator activated
      receptor binding by F-18 and C-11 fatty acids.
AB  - [11C]Acetate, a myocardial PET imaging agent for analysis of oxidative
      metabolism, has potential use in tumor imaging. Aromatic fatty acids display
      antitumor effects with phenylacetate currently in clinical trial. Tumor
      differentiation and cytostasis resulting from phenylacetate treatment may involve
      the peroxisome proliferator-activated receptor alpha (PPARalpha). To examine
      whether aromatic fatty acids are potential imaging agents for PPARalpha or tumors
      in general, [11C]phenylacetic acid (PAA) and [18F]fluorophenyl-acetic acid (FPAA)
      were synthesized and evaluated in EMT-6 tumor bearing mice and 9L-Glioma tumor
      bearing rats and compared to [11C]acetate. [11C]Acetate showed better tumor
      accumulation than PAA or FPAA. The aromatic fatty acids did not directly bind
      PPARalpha as confirmed by a biodistribution study of PAA in PPARalpha -/- mice.

PMID- 11823127
TI  - Novel mixed ligand technetium complexes as 5-HT1A receptor imaging agents.
AB  - The synthesis, characterization and biological evaluation of two novel 3 + 1
      mixed ligand 99mTc-complexes, bearing the 1-(2-methoxyphenylpiperazine) moiety, a
      fragment of the true 5-HT1A antagonist WAY 100635, is reported. Complexes at
      tracer level 99mTcO[(CH3CH2)2NCH2CH2N(CH2CH2S)2][o-CH3OC6H4N(CH2CH2)2NCH2CH2S],
      99mTc-1, and 99mTcO[((CH3)2CH)2NCH2CH2N(CH2CH2S)2][o-CH3OC6H4N
      (CH2CH2)2NCH2CH2S], 99mTc-2, were prepared using 99mTc-glucoheptonate as
      precursor. For structural characterization, the analogous oxorhenium complexes,
      Re-1 and Re-2, were prepared by ligand exchange reaction using ReOCl3(PPh3)2 as
      precursor, and characterized by elemental analysis and spectroscopic methods.
      Complex Re-1 was further characterized by crystallographic analysis. Labeling was
      performed with high yield (>85%) and radiochemical purity (>90%) using very low
      ligand concentration. The structure of 99mTc complexes was established by
      comparative HPLC using the well-characterized oxorhenium analogues as references.
      In vitro binding assays demonstrated the affinity of these complexes for 5-HT1A
      receptors (IC50 : 67 and 45 nM for Re-1 and Re-2 respectively). Biological
      studies in mice showed the ability of 99mTc-1 and 99mTc-2 complexes to cross the
      intact blood-brain barrier (1.4 and 0.9% dose/g, respectively at 1 min post
      inj.). The distribution of these complexes in various regions in rat brain is
      inhomogeneous. The highest ratio between areas reach and poor in 5-HT1A receptors
      was calculated for complex Tc-1 at 60 min p.i. (hippocampus/cerebellum = 1.7).

PMID- 11823128
TI  - PET studies of 18F-memantine in healthy volunteers.
AB  - Previous studies in mice and PET investigations in a Rhesus monkey showed that
      the regional uptake of 18F-memantine could be blocked by pharmacological doses of
      memantine and (+)-MK-801. In the present study, the binding characteristics of
      18F-memantine was examined in five healthy volunteers. In humans, 18F-memantine
      was homogeneously distributed in gray matter i.e. cortex and basal ganglia
      regions, as well as the cerebellum. No radioactive metabolites were detected in
      plasma during the time-frame of the PET studies. The uptake of 18F-memantine in
      receptor-rich regions such as striatum and frontal cortex could be well described
      by a 1-tissue compartment model. The DV" values of all gray matter regions were
      similar and ranged from 15 to 20 ml/ml. The white matter showed lower DV" values
      of 15 +/- 1.4 ml/ml. These results suggest that 18F-memantine distribution in
      human brain does not reflect the regional NMDA receptor concentration, and
      therefore, this radioligand is not suitable for the PET imaging of the NMDA
      receptors.

PMID- 11823129
TI  - Syntheses and pharmacological evaluation of two potent antagonists for dopamine
      D4 receptors: [11C]YM-50001 and N-[2-[4-(4-Chlorophenyl)-piperizin-1-yl]ethyl]-3
      [11C]methoxybenzamide.
AB  - Two benzamide derivatives as dopamine D4 receptor antagonists, YM-50001(4) and N-
      [2-[4-(4-chlorophenyl]piperizin-1-yl]ethyl]-3-methoxybenzamide (9), were labeled
      by positron-emitter (11C), and their pharmacological specificities to dopamine D4
      receptors were examined by quantitative autoradiography and positron emission
      tomography (PET). Radiosyntheses were accomplished by O-methylation of
      corresponding phenol precursors (5 and 10) with [11C]CH3I followed by HPLC
      purifications. In vitro binding on rat brain slices showed different distribution
      patterns and pharmacological properties between the two radioligands. The [11C]4
      showed the highest binding in the striatum, which was inhibited not only by 10
      microM 4 but also by 10 microM raclopride, a selective dopamine D2 receptor
      antagonist. In contrast, [11C]9 showed the highest binding in the cerebral
      cortex, which was inhibited by several D4 receptor antagonists (9, RBI-254, L
      745,870), but not by any other receptor ligands (D1/D5, D2/D3, 5-HT1A, 5-HT2A,
      sigma1 and alpha1) tested. In vivo brain distribution of [11C]9 in rat showed the
      highest uptake in the frontal cortex, a region that has a high density of D4
      receptors. These results indicate that the pharmacological property of [11C]9
      matches the rat brain D4 receptors, but that of [11C]4 rather appears to match
      the rat brain D2 receptors. The results for the benzamide [11C]9 prompted us to
      further evaluate its potential as a PET radioligand for D4 receptors by employing
      PET on monkey brain. Unfortunately, in contrast to rats, neither specific binding
      nor differences in regional uptake of radioactivity were observed in monkey brain
      after intravenous 11C]9 injection. Based on that specific activities of
      radioligands might be critical in mapping the neurotransmitter receptors if they
      are only faintly expressed in the brain, 11C]9 with an extremely high specific
      activity (1810 GBq/micromol) was used for PET study. However, the effort to
      determine the specific binding for D4 failed. These results indicate that both of
      the benzamide derivatives would not be suitable radioligands for D4 receptors
      with PET.

PMID- 11823130
TI  - 201Tl, 99mTc-MIBI, 99mTc-tetrofosmin and 99mTc-furifosmin: relative retention and
      clearance kinetics in retrogradely perfused guinea pig hearts.
AB  - Myocellular kinetics of 201Tl, 99mTc-MIBI, 99mTc-tetrofosmin and 99mTc-furifosmin
      were investigated using retrogradely-perfused guinea-pig hearts. Relative
      retention decreased in the order 99mTc-MIBI ==> 99mTc-tetrofosmin ==> 99mTc
      furifosmin. 201Tl and 99mTc-MIBI exhibited bi- (t1,t2), 99mTc-tetrofosmin and
      99mTc-furifosmin triexponential (t1,t2,t3) time-activity-curves. Latest-phase
      elimination-half-life increased from 201Tl (t2) ==> 99mTc-MIBI (t2) ==> 99mTc
      tetrofosmin (t3) ==> 99mTc-furifosmin (t3), showing a significant increase in
      deteriorating myocardium for all tracers but 99mTc-furifosmin. Delayed
      elimination in deteriorating myocardium explains at least partly the
      redistribution phenomenon of 201Tl, and suggests a similar phenomenon for 99mTc
      MIBI and 99mTc-tetrofosmin.

PMID- 11823131
TI  - 4-[18F]fluoroarylalkylethers via an improved synthesis of n.c.a. 4
      [18F]fluorophenol.
AB  - This paper describes the improved synthesis of n.c.a. 4- 18F]fluorophenol for the
      preparation of 18F-labeled alkylarylethers. Nucleophilic fluorination of
      substituted benzophenone derivatives yielded n.c.a. 4- 18F]fluoro-4'-substituted
      benzophenones with 80- 90% RCY, which were converted to benzoic acid phenylesters
      by treatment with peracetic acid. Strong electron-withdrawing substituents like
      nitro, cyano and trifluoromethyl favor a fluorophenyl-to-oxygen migration
      resulting in the formation of corresponding benzoic acid fluorophenylesters.
      N.c.a. 18F]fluorophenol is almost quantitatively formed after hydrolysis and can
      easily be converted with alkylhalides into n.c.a. 18F]fluoroarylalkylethers.

PMID- 11823132
TI  - A new precursor for the radiosynthesis of [18F]FLT.
AB  - In order to improve the [18F]FLT production for nuclear medical purposes, the
      syntheses and labeling results obtained with six new thymidine derivatives
      involving an alternative protection group strategy are described. The syntheses
      of the FLT-labeling precursors were performed using the following protection
      groups at the 5'-O-position: trityl (Tr) and 4,4'-dimethoxytrityl (DMTr).
      Formation of an electrophilic center at the 3'-carbon was achieved with
      methylsulfonyl, p-toluenesulfonyl and 4-nitrobenzenesulfonyl groups. The major
      difference to previous accomplishments rested upon the 3-N-Boc-protection of the
      FLT-labeling precursors avoiding the deprotection with ceric ammonium nitrate
      (CAN). With CAN, a precipitate was formed which was found to interact
      unfavourably with synthesis automation. Here, deprotection resulted in
      homogeneous solutions which could immediately be loaded on HPLC. The
      radiosyntheses were performed with high doses of [18F]fluoride to obtain
      realistic results for routine production of the clinically interesting
      radiopharmaceutical, [18F]FLT. It was shown that the nosylated precursors were
      more favorable for radiofluorination than the mesylated or tosylated derivatives.
      A positive effect on the radiochemical yield was found with DMTr in comparison to
      Tr. Best results were obtained using 3-N-Boc-1-[5-O-(4,4'-dimethoxytrityl)-3-O
      nosyl-2-deoxy-beta-D-lyxofuranosyl]thymine yielding 1.7 GBq (19.8% EOB) whithin
      85 minutes.

PMID- 11823147
TI  - Can you die of a brokenheart?

PMID- 11823133
TI  - Chemical impurities in [18F]FDG preparations produced by solid-phase 18F
      fluorination.
AB  - [18F]FDG was produced by solid-phase 18F-fluorination (resin method) and chemical
      impurities were determined in the [18F]FDG preparations by ion chromatography.
      The major chemical impurities were D-glucose (90.5 +/- 6.4 microg/mL), 2-chloro-2
      deoxy-D-glucose (11.8 +/- 2.7 microg/mL), and D-mannose (1.7 +/- 0.7 microg/mL),
      which were expected to be present by considering the synthetic routes. An FDG
      mass (0.5 +/- 0.2 microg/mL) was also detected in the preparations. No notable
      radiochemical impurities, including 2-[18F]fluoro-2-deoxy-D-mannose, were
      detected in the [18F]FDG preparations. Thus, the levels of several chemical
      impurities were determined in the [18F]FDG preparations produced by solid-phase
      18F-fluorination.

PMID- 11823148
TI  - Clot filters: preventing strokes during carotid artery procedures.

PMID- 11823149
TI  - Heart lines: vitamin conflicts.

PMID- 11823150
TI  - Heart lines: dallas bed rest study.

PMID- 11823151
TI  - Heart lines: taking a marathon to heart.

PMID- 11823152
TI  - Ask the Doctor: Because I had a lot of rhythm abnormalities after my heart attack
      a few years ago, my doctor gave me an implantable defibrillator. I've gotten so
      used to it that I forgot I even had it until a few weeks ago when I was sitting
      at dinner and felt a big thump in my chest that nearly knocked me out of my
      chair. I went to my cardiologist, who did some tests and told me not to worry
      about it. As I see it, I just died and was rescued by this thing. Shouldn't
      something more be done for me?

PMID- 11823153
TI  - Ask the Doctor: I keep reading that homocysteine is an important new risk factor
      for heart disease, but my doctor says this test is not yet "ready for prime
      time." What's the holdup?

PMID- 11823154
TI  - Ask the Doctor: I know that most of the cholesterol-lowering statin drugs are
      supposed to be safe. But I am still shaken up by the news that one of these
      drugs, Baycol, caused several deaths due to muscle damage. If the rest of these
      drugs can also cause the same problem, how can any of them be considered safe?

PMID- 11823155
TI  - Ask the Doctor: Ive read about the new guidelines for cholesterol and, like
      almost everyone I know, my LDL cholesterol is above the "optimal" level of less
      than 100 mg/dL. For someone like me, with an LDL level of 145 mg/dL but no other
      major risk factors and no known heart disease, the guidelines encourage diet and
      lifestyle changes to lower my LDL. What I don't understand is why I shouldn't
      just go on a statin?

PMID- 11823156
TI  - Living to 100: What's the Secret?

PMID- 11823157
TI  - Brain health: a progress report.

PMID- 11823158
TI  - Surgery: a short, practical guide to hernias.

PMID- 11823159
TI  - Research at Harvard: Gene therapy, circa 2002.

PMID- 11823160
TI  - Research at Harvard: Statins and the older blood vessel: a good match?

PMID- 11823162
TI  - Research at Harvard: HRT and dry eyes: what s the connection?

PMID- 11823161
TI  - Research at Harvard: A passive approach to AIDS.

PMID- 11823163
TI  - By the way doctor: learning breast self-examination.

PMID- 11823164
TI  - By the way doctor: preventing falls.

PMID- 11823165
TI  - The benefits of positive psychology.

PMID- 11823166
TI  - Disaster and trauma.

PMID- 11823167
TI  - In brief: is child sexual abuse declining?

PMID- 11823169
TI  - C-reactive protein: a new marker for cardiac risk.

PMID- 11823168
TI  - Good for the heart but not for the prostate? The alpha-linolenic acid dilemma.

PMID- 11823170
TI  - Sex and prostate cancer: a new risk factor?

PMID- 11823171
TI  - On call. I saw on TV that President Bush had a complete checkup and that his
      heart rate was 44. I know that the vice president recently got a pacemaker; why
      didn't the president get one, too?

PMID- 11823177
TI  - Multiple alternate transcripts direct the biosynthesis of microcystin, a
      cyanobacterial nonribosomal peptide.
AB  - The mcyABCDEFGHIJ gene cluster of Microcystis aeruginosa encodes the mixed
      polyketide synthase/nonribosomal peptide synthetase (microcystin synthetase)
      which is responsible for biosynthesis of the potent liver toxin microcystin. The
      sequence and orientation of the mcy genes have previously been reported, but no
      transcriptional analysis had been performed prior to this study. The
      mcyABCDEFGHIJ genes are transcribed as two polycistronic operons, mcyABC and
      mcyDEFGHIJ, from a central bidirectional promoter between mcyA and mcyD. Two
      transcription start sites were detected for both mcyA and mcyD when cells were
      exposed to light intensities of 68 and 16 micromol of photons m(-2) s(-1). The
      start sites, located 206 and 254 bp upstream of the translational start for mcyD
      under high and low light conditions, respectively, indicate long untranslated
      leader regions. Putative transcription start sites were also identified for mcyE,
      mcyF, mcyG, mcyH, mcyI, and mcyJ but not for mcyB and mcyC. A combination of
      reverse transcription-PCR and rapid amplification of cDNA ends was employed
      throughout this work, which may have been one of the first transcriptional
      analyses of a large nonribosomal polyketide gene cluster.

PMID- 11823178
TI  - Enhanced levels of cold shock proteins in Listeria monocytogenes LO28 upon
      exposure to low temperature and high hydrostatic pressure.
AB  - Listeria monocytogenes is a psychrotrophic food-borne pathogen that is
      problematic for the food industry because of its ubiquitous distribution in
      nature and its ability to grow at low temperatures and in the presence of high
      salt concentrations. Here we demonstrate that the process of adaptation to low
      temperature after cold shock includes elevated levels of cold shock proteins
      (CSPs) and that the levels of CSPs are also elevated after treatment with high
      hydrostatic pressure (HHP). Two-dimensional gel electrophoresis combined with
      Western blotting performed with anti-CspB of Bacillus subtilis was used to
      identify four 7-kDa proteins, designated Csp1, Csp2, Csp3, and Csp4. In addition,
      Southern blotting revealed four chromosomal DNA fragments that reacted with a csp
      probe, which also indicated that a CSP family is present in L. monocytogenes
      LO28. After a cold shock in which the temperature was decreased from 37 degrees C
      to 10 degrees C the levels of Csp1 and Csp3 increased 10- and 3.5-fold,
      respectively, but the levels of Csp2 and Csp4 were not elevated. Pressurization
      of L. monocytogenes LO28 cells resulted in 3.5- and 2-fold increases in the
      levels of Csp1 and Csp2, respectively. Strikingly, the level of survival after
      pressurization of cold-shocked cells was 100-fold higher than that of cells
      growing exponentially at 37 degrees C. These findings imply that cold-shocked
      cells are protected from HHP treatment, which may affect the efficiency of
      combined preservation techniques.

PMID- 11823179
TI  - FK506 binding protein from the hyperthermophilic archaeon Pyrococcus horikoshii
      suppresses the aggregation of proteins in Escherichia coli.
AB  - The 29-kDa FK506 binding protein (FKBP) gene is the only peptidyl-prolyl cis
      trans isomerase (PPIase) gene in the genome of Pyrococcus horikoshii. We
      characterized the function of this FKBP (PhFKBP29) and used it to increase the
      production yield of soluble recombinant protein in Escherichia coli. The PPIase
      activity (k(cat)/K(m)) of PhFKBP29 was found to be much lower than that of other
      archaeal 16- to 18-kDa FKBPs by a chymotrypsin-coupled assay of the oligo
      peptidyl substrate at 15 degrees C. Besides this low PPIase activity, PhFKBP29
      showed chaperone-like protein folding activity which enhanced the refolding yield
      of chemically unfolded rhodanese in vitro. In addition, it suppressed thermal
      protein aggregation in a temperature range of 45 to 100 degrees C. When the
      PhFKBP29 gene was coexpressed with the recombinant Fab fragment gene of the anti
      hen egg lysozyme antibody in the cytoplasm of E. coli, whose expressed product
      tended to form an inactive aggregate in E. coli, it improved the yield of the
      soluble Fab fragments with antibody specificity. PhFKBP29 exerted protein folding
      and aggregation suppression in E. coli cells.

PMID- 11823180
TI  - Occurrence and phenotypic characterization of Yersinia ruckeri strains with
      biofilm-forming capacity in a rainbow trout farm.
AB  - The presence of Yersinia ruckeri in a French fish farm was investigated. Y.
      ruckeri was isolated mainly from algae and sediment samples rather than from
      water. Twenty-two Y. ruckeri isolates were obtained, and three strains were
      distinguished by enterobacterial repetitive intergenic consensus PCR
      amplification. These strains were able to adhere to solid supports. This
      characteristic was correlated with flagellum-mediated motility. Killing
      experiments showed that sessile cells were more resistant to oxolinic acid than
      their planktonic counterparts. Our results demonstrate that surface colonization
      of fish farm tanks by Y. ruckeri biofilms is a potential source of recurrent
      infection for extended periods of time.

PMID- 11823181
TI  - Bacteria associated with hazelnut (Corylus avellana L.) decline are of two
      groups: Pseudomonas avellanae and strains resembling P. syringae pv. syringae.
AB  - A total of 118 fluorescent pseudomonads associated with hazelnut decline, which
      has been occurring for many years in different areas of northern Greece and
      Italy, were assessed by performing a repetitive PCR analysis with enterobacterial
      repetitive intergenic consensus, box element, and repetive extragenic palindromic
      primer sets, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE)
      of whole-cell protein extracts, a carbon compound utilization analysis, and an
      analysis to determine the presence of the syrB gene. A subset of 53 strains was
      also characterized by amplified 16S ribosomal DNA restriction analysis (ARDRA) by
      using nine restriction endonucleases. The virulence of 40 representative strains
      was assessed by using serial doses. The pathogenic specificities of the strains
      were also verified. ARDRA carried out with HinfI revealed two main groups of
      strains, groups A and B, which exhibited a level of similarity of 57%. The other
      eight restriction endonucleases used did not separate the strains. In addition, a
      cluster analysis performed by the unweighted pair group method using arithmetic
      averages after repetitive PCR and SDS-PAGE of protein extracts also revealed the
      same two groups. Furthermore, the differential utilization of some carbon
      compounds made it possible to differentiate the groups. Virulence assessment
      clearly indicated that the group A strains are very virulent, whereas the group B
      strains proved to be mildly virulent for hazelnut. Group A included the strains
      isolated in northern Greece and central Italy (i.e., the province of Viterbo);
      these strains do not have the syrB gene, are pathogenically restricted to Corylus
      avellana, and belong to Pseudomonas avellanae. Group B includes the other strains
      obtained from hazelnut cultivated in Piedmont, Campania, Latium, Sicily, and
      Sardinia. They represent a distinct taxon closely related to Pseudomonas syringae
      pv. syringae.

PMID- 11823182
TI  - Molecular analysis of Dehalococcoides 16S ribosomal DNA from chloroethene
      contaminated sites throughout North America and Europe.
AB  - The environmental distribution of Dehalococcoides group organisms and their
      association with chloroethene-contaminated sites were examined. Samples from 24
      chloroethene-dechlorinating sites scattered throughout North America and Europe
      were tested for the presence of members of the Dehalococcoides group by using a
      PCR assay developed to detect Dehalococcoides 16S rRNA gene (rDNA) sequences.
      Sequences identified by sequence analysis as sequences of members of the
      Dehalococcoides group were detected at 21 sites. Full dechlorination of
      chloroethenes to ethene occurred at these sites. Dehalococcoides sequences were
      not detected in samples from three sites at which partial dechlorination of
      chloroethenes occurred, where dechlorination appeared to stop at 1,2-cis
      dichloroethene. Phylogenetic analysis of the 16S rDNA amplicons confirmed that
      Dehalococcoides sequences formed a unique 16S rDNA group. These 16S rDNA
      sequences were divided into three subgroups based on specific base substitution
      patterns in variable regions 2 and 6 of the Dehalococcoides 16S rDNA sequence.
      Analyses also demonstrated that specific base substitution patterns were
      signature patterns. The specific base substitutions distinguished the three
      sequence subgroups phylogenetically. These results demonstrated that members of
      the Dehalococcoides group are widely distributed in nature and can be found in a
      variety of geological formations and in different climatic zones. Furthermore,
      the association of these organisms with full dechlorination of chloroethenes
      suggests that they are promising candidates for engineered bioremediation and may
      be important contributors to natural attenuation of chloroethenes.

PMID- 11823183
TI  - Numerical dominance and phylotype diversity of marine Rhodobacter species during
      early colonization of submerged surfaces in coastal marine waters as determined
      by 16S ribosomal DNA sequence analysis and fluorescence in situ hybridization.
AB  - Early stages of surface colonization in coastal marine waters appear to be
      dominated by the marine Rhodobacter group of the alpha subdivision of the
      division Proteobacteria (alpha-Proteobacteria). However, the quantitative
      contribution of this group to primary surface colonization has not been
      determined. In this study, glass microscope slides were incubated in a salt marsh
      tidal creek for 3 or 6 days. Colonizing bacteria on the slides were examined by
      fluorescence in situ hybridization by employing DNA probes targeting 16S or 23S
      rRNA to identify specific phylogenetic groups. Confocal laser scanning microscopy
      was then used to quantify and track the dynamics of bacterial primary colonists
      during the early stages of surface colonization and growth. More than 60% of the
      surface-colonizing bacteria detectable by fluorescence staining (Yo-Pro-1) could
      also be detected with the Bacteria domain probe EUB338. Archaea were not detected
      on the surfaces and did not appear to participate in surface colonization. Of the
      three subdivisions of the Proteobacteria examined, the alpha-Proteobacteria were
      the most abundant surface-colonizing organisms. More than 28% of the total
      bacterial cells and more than 40% of the cells detected by EUB338 on the surfaces
      were affiliated with the marine Rhodobacter group. Bacterial abundance increased
      significantly on the surfaces during short-term incubation, mainly due to the
      growth of the marine Rhodobacter group organisms. These results demonstrated the
      quantitative importance of the marine Rhodobacter group in colonization of
      surfaces in salt marsh waters and confirmed that at least during the early stages
      of colonization, this group dominated the surface-colonizing bacterial
      assemblage.

PMID- 11823184
TI  - Phylogenetic composition of bacterioplankton assemblages from the Arctic Ocean.
AB  - We analyzed the phylogenetic composition of bacterioplankton assemblages in 11
      Arctic Ocean samples collected over three seasons (winter-spring 1995, summer
      1996, and summer-fall 1997) by sequencing cloned fragments of 16S rRNA genes. The
      sequencing effort was directed by denaturing gradient gel electrophoresis (DGGE)
      screening of samples and the clone libraries. Sequences of 88 clones fell into
      seven major lineages of the domain Bacteria: alpha(36%)-, gamma(32%)-, delta(14%)
      , and epsilon(1%)-Proteobacteria; Cytophaga-Flexibacter-Bacteroides spp. (9%);
      Verrucomicrobium spp. (6%); and green nonsulfur bacteria (2%). A total of 34% of
      the cloned sequences (excluding clones in the SAR11 and Roseobacter groups) had
      sequence similarities that were <94% compared to previously reported sequences,
      indicating the presence of novel sequences. DGGE fingerprints of the selected
      samples showed that most of the bands were common to all samples in all three
      seasons. However, additional bands representing sequences related to Cytophaga
      and Polaribacter species were found in samples collected during the summer and
      fall. Of the clones in a library generated from one sample collected in spring of
      1995, 50% were the same and were most closely affiliated (99% similarity) with
      Alteromonas macleodii, while 50% of the clones in another sample were most
      closely affiliated (90 to 96% similarity) with Oceanospirillum sp. The majority
      of the cloned sequences were most closely related to uncultured, environmental
      sequences. Prominent among these were members of the SAR11 group. Differences
      between mixed-layer and halocline samples were apparent in DGGE fingerprints and
      clone libraries. Sequences related to alpha-Proteobacteria (dominated by SAR11)
      were abundant (52%) in samples from the mixed layer, while sequences related to
      gamma-proteobacteria were more abundant (44%) in halocline samples. Two bands
      corresponding to sequences related to SAR307 (common in deep water) and the high
      G+C gram-positive bacteria were characteristic of the halocline samples.

PMID- 11823185
TI  - Displacement of Escherichia coli O157:H7 from rumen medium containing prebiotic
      sugars.
AB  - A fed-batch, anaerobic culture system was developed to assess the behavior of
      Escherichia coli O157:H7 in a rumen-like environment. Fermentation medium
      consisted of either 50% (vol/vol) raw or sterile rumen fluid and 50% phosphate
      buffer. Additional rumen fluid was added twice per day, and samples were removed
      three times per day to simulate the exiting of digesta and microbes from the
      rumen environment under typical feeding regimens. With both types of medium,
      anaerobic and enteric bacteria reached 10(10) and 10(4) cells/ml, respectively,
      and were maintained at these levels for at least 5 days. When a rifampin
      resistant strain of E. coli O157:H7 was inoculated into medium containing raw
      rumen fluid, growth did not occur. In contrast, when this strain was added to
      sterile rumen fluid medium, cell densities increased from 10(6) to 10(9) CFU/ml
      within 24 h. Most strains of E. coli O157:H7 are unable to ferment sorbitol;
      therefore, we assessed whether the addition of sorbitol as the only added
      carbohydrate could be used to competitively exclude E. coli O157:H7 from the
      culture system. When inoculated into raw rumen broth containing 3 g of sorbitol
      per liter, E. coli O157:H7 was displaced within 72 h. The addition of other
      competitive sugars, such as L-arabinose, trehalose, and rhamnose, to rumen medium
      gave similar results. However, whenever E. coli O157:H7 was grown in sterile
      rumen broth containing sorbitol, sorbitol-positive mutants appeared. These
      results suggest that a robust population of commensal ruminal microflora is
      required to invoke competitive exclusion of E. coli O157:H7 by the addition of
      "nonfermentable" sugars and that this approach may be effective as a preharvest
      strategy for reducing carriage of E. coli O157:H7 in the rumen.

PMID- 11823186
TI  - Novel bacterial membrane surface display system using cell wall-less L-forms of
      Proteus mirabilis and Escherichia coli.
AB  - We describe a novel membrane surface display system that allows the anchoring of
      foreign proteins in the cytoplasmic membrane (CM) of stable, cell wall-less L
      form cells of Escherichia coli and Proteus mirabilis. The reporter protein,
      staphylokinase (Sak), was fused to transmembrane domains of integral membrane
      proteins from E. coli (lactose permease LacY, preprotein translocase SecY) and P.
      mirabilis (curved cell morphology protein CcmA). Both L-form strains
      overexpressed fusion proteins in amounts of 1 to 100 microg ml(-1), with higher
      expression for those with homologous anchor motifs. Various experimental
      approaches, e.g., cell fractionation, Percoll gradient purification, and
      solubilization of the CM, demonstrated that the fusion proteins are tightly bound
      to the CM and do not form aggregates. Trypsin digestion, as well as electron
      microscopy of immunogold-labeled replicas, confirmed that the protein was
      localized on the outside surface. The displayed Sak showed functional activity,
      indicating correct folding. This membrane surface display system features
      endotoxin-poor organisms and can provide a novel platform for numerous
      applications.

PMID- 11823187
TI  - Osmoregulation and fungicide resistance: the Neurospora crassa os-2 gene encodes
      a HOG1 mitogen-activated protein kinase homologue.
AB  - Neurospora crassa osmosensitive (os) mutants are sensitive to high osmolarity and
      therefore are unable to grow on medium containing 4% NaCl. We found that os-2 and
      os-5 mutants were resistant to the phenylpyrrole fungicides fludioxonil and
      fenpiclonil. To understand the relationship between osmoregulation and fungicide
      resistance, we cloned the os-2 gene by using sib selection. os-2 encodes a
      putative mitogen-activated protein (MAP) kinase homologous to HOG1 and can
      complement the osmosensitive phenotype of a Saccharomyces cerevisiae hog1 mutant.
      We sequenced three os-2 alleles and found that all of them were null with either
      frameshift or nonsense point mutations. An os-2 gene replacement mutant also was
      generated and was sensitive to high osmolarity and resistant to phenylpyrrole
      fungicides. Conversely, os-2 mutants transformed with the wild-type os-2 gene
      could grow on media containing 4% NaCl and were sensitive to phenylpyrrole
      fungicides. Fludioxonil stimulated intracellular glycerol accumulation in wild
      type strains but not in os-2 mutants. Fludioxonil also caused wild-type conidia
      and hyphal cells to swell and burst. These results suggest that the hyperosmotic
      stress response pathway of N. crassa is the target of phenylpyrrole fungicides
      and that fungicidal effects may result from a hyperactive os-2 MAP kinase
      pathway.

PMID- 11823188
TI  - Marine bacteria cause false-positive results in the Colilert-18 rapid
      identification test for Escherichia coli in Florida waters.
AB  - The Colilert-18 system for enumeration of total coliforms and Escherichia coli is
      approved by the U.S. Environmental Protection Agency for use in drinking water
      analysis and is also used by various agencies and research studies for
      enumeration of indicator organisms in fresh and saline waters. During monitoring
      of Pinellas County, Fla., marine waters, estimates of E. coli numbers (by
      Colilert-18) frequently exceeded fecal coliform counts (by membrane filtration)
      by 1 to 3 orders of magnitude. Samples from freshwater sites did not display
      similar discrepancies. Fecal coliforms, including E. coli, could be cultured from
      100% of yellow fluorescent wells (denoting E. coli-positive results) inoculated
      with freshwater samples but could be cultured from only 17.1% of the "positive"
      wells inoculated with marine samples. Ortho-nitrophenyl-beta-D-galactopyranoside
      (ONPG)-positive or 4-methylumbelliferyl-beta-D-glucuronide (MUG)-positive
      noncoliform bacteria were readily cultured from Colilert-18 test wells inoculated
      with marine samples. Filtered cell-free seawater did not cause false positives.
      Coculture preparations of as few as 5 CFU of Vibrio cholerae (ONPG positive) and
      Providencia sp. (MUG positive) ml(-1) inoculated into Colilert-18 caused false
      positive E. coli results. Salinity conditions influenced coculture results, as
      the concentration of coculture inoculum required to cause false positives in most
      wells increased from about 5 CFU ml(-1) in seawater diluted 1:10 with freshwater
      to approximately equal to 5,000 CFU ml(-1) in seawater diluted 1:20 with
      freshwater. Estimated E. coli numbers in various marine water samples processed
      at the 1:10 dilution ranged from 10 to 7,270 CFU.100 ml(-1), while E. coli
      numbers in the same samples processed at the 1:20 dilution did not exceed 40
      CFU.100 ml(-1). The lower estimates of E. coli numbers corresponded well with
      fecal coliform counts by membrane filtration. This study indicates that
      assessment of E. coli in subtropical marine waters by Colilert-18 is not accurate
      when the recommended 1:10 sample dilution is used. The results suggest that
      greater dilution may diminish the false-positive problem, but further study of
      this possibility is recommended.

PMID- 11823190
TI  - Competitive exclusion of Salmonella enterica serovar Enteritidis by Lactobacillus
      crispatus and Clostridium lactatifermentans in a sequencing fed-batch culture.
AB  - Competitive exclusion of Salmonella enterica serovar Enteritidis by a mixed
      culture of Lactobacillus crispatus and Clostridium lactatifermentans was studied
      in a sequencing fed-batch reactor mimicking the cecal ecophysiology of broiler
      chickens. Growth of serovar Enteritidis was inhibited by a mixed culture of L.
      crispatus and C. lactatifermentans at pH 5.8 but not by a monoculture of L.
      crispatus at the same pH. Moreover, experiments performed at pH 7.0 did not show
      growth inhibition of serovar Enteritidis. L. crispatus fermented lactose to
      lactate, and C. lactatifermentans fermented the lactate to acetate and propionate
      in a mixed culture of L. crispatus and C. lactatifermentans growing on lactose.
      In contrast, only lactate was produced from lactose by a monoculture of L.
      crispatus. At pH 5.8 considerable concentrations of acetate and propionate were
      present as undissociated acids, whereas only trace levels of undissociated
      lactate were present at pH 5.8 due to the low pK(a) of lactate. At pH 7.0 all
      three acids were present in their dissociated forms. We conclude that a mixed
      culture of L. crispatus and C. lactatifermentans inhibits growth of serovar
      Enteritidis under cecal growth conditions. The undissociated forms of acetate and
      propionate produced in the mixed culture inhibited the growth of serovar
      Enteritidis.

PMID- 11823189
TI  - Regulation of endo-acting glycosyl hydrolases in the hyperthermophilic bacterium
      Thermotoga maritima grown on glucan- and mannan-based polysaccharides.
AB  - The genome sequence of the hyperthermophilic bacterium Thermotoga maritima
      encodes a number of glycosyl hydrolases. Many of these enzymes have been shown in
      vitro to degrade specific glycosides that presumably serve as carbon and energy
      sources for the organism. However, because of the broad substrate specificity of
      many glycosyl hydrolases, it is difficult to determine the physiological
      substrate preferences for specific enzymes from biochemical information. In this
      study, T. maritima was grown on a range of polysaccharides, including barley beta
      glucan, carboxymethyl cellulose, carob galactomannan, konjac glucomannan, and
      potato starch. In all cases, significant growth was observed, and cell densities
      reached 10(9) cells/ml. Northern blot analyses revealed different substrate
      dependent expression patterns for genes encoding the various endo-acting beta
      glycosidases; these patterns ranged from strong expression to no expression under
      the conditions tested. For example, cel74 (TM0305), a gene encoding a putative
      beta-specific endoglucananse, was strongly expressed on all substrates tested,
      including starch, while no evidence of expression was observed on any substrate
      for lam16 (TM0024), xyl10A (TM0061), xyl10B (TM0070), and cel12A (TM1524), which
      are genes that encode a laminarinase, two xylanases, and an endoglucanase,
      respectively. The cel12B (TM1525) gene, which encodes an endoglucanase, was
      expressed only on carboxymethyl cellulose. An extracellular mannanase encoded by
      man5 (TM1227) was expressed on carob galactomannan and konjac glucomannan and to
      a lesser extent on carboxymethyl cellulose. An unexpected result was the finding
      that the cel5A (TM1751) and cel5B (TM1752) genes, which encode putative
      intracellular beta-specific endoglucanases, were induced only when T. maritima
      was grown on konjac glucomannan. To investigate the biochemical basis of this
      finding, the recombinant forms of Man5 (M(r), 76,900) and Cel5A (M(r), 37,400)
      were expressed in Escherichia coli and characterized. Man5, a T. maritima
      extracellular enzyme, had a melting temperature of 99 degrees C and an optimun
      temperature of 90 degrees C, compared to 90 and 80 degrees C, respectively, for
      the intracellular enzyme Cel5A. While Man5 hydrolyzed both galactomannan and
      glucomannan, no activity was detected on glucans or xylans. Cel5A, however, not
      only hydrolyzed barley beta-glucan, carboxymethyl cellulose, xyloglucan, and
      lichenin but also had activity comparable to that of Man5 on galactomannan and
      higher activity than Man5 on glucomannan. The biochemical characteristics of
      Cel5A, the fact that Cel5A was induced only when T. maritima was grown on
      glucomannan, and the intracellular localization of Cel5A suggest that the
      physiological role of this enzyme includes hydrolysis of glucomannan
      oligosaccharides that are transported following initial hydrolysis by
      extracellular glycosidases, such as Man5.

PMID- 11823191
TI  - Characterization and application of xylene monooxygenase for multistep
      biocatalysis.
AB  - Xylene monooxygenase of Pseudomonas putida mt-2 catalyzes multistep oxidations of
      one methyl group of toluene and xylenes. Recombinant Escherichia coli expressing
      the monooxygenase genes xylM and xylA catalyzes the oxygenation of toluene,
      pseudocumene, the corresponding alcohols, and the corresponding aldehydes, all by
      a monooxygenation type of reaction (B. Buhler, A. Schmid, B. Hauer, and B.
      Witholt, J. Biol. Chem. 275:10085-10092, 2000). Using E. coli expressing xylMA,
      we investigated the kinetics of this one-enzyme three-step biotransformation. We
      found that unoxidized substrates like toluene and pseudocumene inhibit the second
      and third oxygenation steps and that the corresponding alcohols inhibit the third
      oxygenation step. These inhibitions might promote the energetically more
      favorable alcohol and aldehyde dehydrogenations in the wild type. Growth of E.
      coli was strongly affected by low concentrations of pseudocumene and its
      products. Toxicity and solubility problems were overcome by the use of a two
      liquid-phase system with bis(2-ethylhexyl)phthalate as the carrier solvent,
      allowing high overall substrate and product concentrations. In a fed-batch-based
      two-liquid-phase process with pseudocumene as the substrate, we observed the
      consecutive accumulation of aldehyde, acid, and alcohol. Our results indicate
      that, depending on the reaction conditions, product formation could be directed
      to one specific product.

PMID- 11823192
TI  - Sources and species of cryptosporidium oocysts in the Wachusett Reservoir
      watershed.
AB  - Understanding the behavior of Cryptosporidium oocysts in the environment is
      critical to developing improved watershed management practices for protection of
      the public from waterborne cryptosporidiosis. Analytical methods of improved
      specificity and sensitivity are essential to this task. We developed a nested PCR
      restriction fragment length polymorphism assay that allows detection of a single
      oocyst in environmental samples and differentiates the human pathogen
      Cryptosporidium parvum from other Cryptosporidium species. We tested our method
      on surface water and animal fecal samples from the Wachusett Reservoir watershed
      in central Massachusetts. We also directly compared results from our method with
      those from the immunofluorescence microscopy assay recommended in the Information
      Collection Rule. Our results suggest that immunofluorescence microscopy may not
      be a reliable indicator of public health risk for waterborne cryptosporidiosis.
      Molecular and environmental data identify both wildlife and dairy farms as
      sources of oocysts in the watershed, implicate times of cold water temperatures
      as high-risk periods for oocyst contamination of surface waters, and suggest that
      not all oocysts in the environment pose a threat to public health.

PMID- 11823193
TI  - Antimicrobial resistance of Escherichia coli O157 isolated from humans, cattle,
      swine, and food.
AB  - A total of 361 Escherichia coli O157 isolates, recovered from humans, cattle,
      swine, and food during the years 1985 to 2000, were examined to better understand
      the prevalence of antimicrobial resistance among these organisms. Based on broth
      microdilution results, 220 (61%) of the isolates were susceptible to all 13
      antimicrobials tested. Ninety-nine (27%) of the isolates, however, were resistant
      to tetracycline, 93 (26%) were resistant to sulfamethoxazole, 61 (17%) were
      resistant to cephalothin, and 48 (13%) were resistant to ampicillin. Highest
      frequencies of resistance occurred among swine isolates (n = 70), where 52 (74%)
      were resistant to sulfamethoxazole, 50 (71%) were resistant to tetracycline, 38
      (54%) were resistant to cephalothin, and 17 (24%) were resistant to ampicillin.
      Based on the presence of Shiga toxin genes as determined by PCR, 210 (58%) of the
      isolates were identified as Shiga toxin-producing E. coli (STEC). Among these,
      resistance was generally low, yet 21 (10%) were resistant to sulfamethoxazole and
      19 (9%) were resistant to tetracycline. Based on latex agglutination, 189 (52%)
      of the isolates were identified as E. coli O157:H7, among which 19 (10%) were
      resistant to sulfamethoxazole and 16 (8%) were resistant to tetracycline. The
      data suggest that selection pressure imposed by the use of tetracycline
      derivatives, sulfa drugs, cephalosporins, and penicillins, whether
      therapeutically in human and veterinary medicine or as prophylaxis in the animal
      production environment, is a key driving force in the selection of antimicrobial
      resistance in STEC and non-STEC O157.

PMID- 11823194
TI  - L-glucitol catabolism in Stenotrophomonas maltophilia Ac.
AB  - The carbohydrate catabolism of the bacterium Stenotrophomonas maltophilia Ac
      (previously named Pseudomonas sp. strain Ac), which is known to convert the
      unnatural polyol L-glucitol to D-sorbose during growth on the former as the sole
      source of carbon and energy, was studied in detail. All enzymes operating in a
      pathway that channels L-glucitol via D-sorbose into compounds of the intermediary
      metabolism were demonstrated, and for some prominent reactions the products of
      conversion were identified. D-Sorbose was converted by C-3 epimerization to D
      tagatose, which, in turn, was isomerized to D-galactose. D-Galactose was the
      initial substrate of the De Ley-Doudoroff pathway, involving reactions of NAD
      dependent oxidation of D-galactose to D-galactonate, its dehydration to 2-keto-3
      deoxy-D-galactonate, and its phosphorylation to 2-keto-3-deoxy-D-galactonate 6
      phosphate. Finally, aldol cleavage yielded pyruvate and D-glycerate 3-phosphate
      as the central metabolic intermediates.

PMID- 11823196
TI  - Novel fungitoxicity assays for inhibition of germination-associated adhesion of
      Botrytis cinerea and Puccinia recondita spores.
AB  - Botrytis cinerea and Puccinia recondita spores adhere strongly to polystyrene
      microtiter plates coincident with germination. We developed assays for inhibition
      of spore adhesion in 96-well microtiter plates by using sulforhodamine B staining
      to quantify the adherent spores. In both organisms, fungicides that inhibited
      germination strongly inhibited spore adhesion, with 50% effective concentrations
      (EC(50)s) comparable to those for inhibition of germination. In contrast,
      fungicides that acted after germination in B. cinerea inhibited spore adhesion to
      microtiter plates only at concentrations much higher than their EC(50)s for
      inhibition of mycelial growth. Similarly, in P. recondita the ergosterol
      biosynthesis inhibitors myclobutanil and fenbuconazole acted after germination
      and did not inhibit spore adhesion. The assays provide a rapid, high-throughput
      alternative to traditional spore germination assays and may be applicable to
      other fungi.

PMID- 11823195
TI  - Expression of antisense RNA targeted against Streptococcus thermophilus
      bacteriophages.
AB  - Antisense RNA complementary to a putative helicase gene (hel3.1) of a cos-type
      Streptococcus thermophilus bacteriophage was used to impede the proliferation of
      a number of cos-type S. thermophilus bacteriophages and one pac-type
      bacteriophage. The putative helicase gene is a component of the Sfi21-type DNA
      replication module, which is found in a majority of the S. thermophilus
      bacteriophages of industrial importance. All bacteriophages that strongly
      hybridized a 689-bp internal hel3.1 probe were sensitive to the expression of
      antisense hel3.1 RNA. A 40 to 70% reduction in efficiency of plaquing (EOP) was
      consistently observed, with a concomitant decrease in plaque size relative to
      that of the S. thermophilus parental strain. When progeny were released, the
      burst size was reduced. Growth curves of S. thermophilus NCK1125, in the presence
      of variable levels of bacteriophage kappa3, showed that antisense hel3.1
      conferred protection, even at a multiplicity of infection of approximately 1.0.
      When the hel3.1 antisense RNA cassette was expressed in cis from the kappa3
      derived phage-encoded resistance (PER) plasmid pTRK690::ori3.1, the EOP for
      bacteriophages sensitive to PER and antisense targeting was reduced to between
      10(-7) and 10(-8), beyond the resistance conferred by the PER element alone (less
      than 10(-6)). These results illustrate the first successful applications of
      antisense RNA and explosive delivery of antisense RNA to inhibit the
      proliferation of S. thermophilus bacteriophages.

PMID- 11823197
TI  - Effect of commercial-scale high-temperature, short-time pasteurization on the
      viability of Mycobacterium paratuberculosis in naturally infected cows' milk.
AB  - Raw cows' milk naturally infected with Mycobacterium paratuberculosis was
      pasteurized with an APV HXP commercial-scale pasteurizer (capacity 2,000
      liters/h) on 12 separate occasions. On each processing occasion, milk was
      subjected to four different pasteurization treatments, viz., 73 degrees C for 15
      s or 25 s with and without prior homogenization (2,500 lb/in(2) in two stages),
      in an APV Manton Gaulin KF6 homogenizer. Raw and pasteurized milk samples were
      tested for M. paratuberculosis by immunomagnetic separation (IMS)-PCR (to detect
      the presence of bacteria) and culture after decontamination with 0.75% (wt/vol)
      cetylpyridinium chloride for 5 h (to confirm bacterial viability). On 10 of the
      12 processing occasions, M. paratuberculosis was detectable by IMS-PCR, culture,
      or both in either raw or pasteurized milk. Overall, viable M. paratuberculosis
      was cultured from 4 (6.7%) of 60 raw and 10 (6.9%) of 144 pasteurized milk
      samples. On one processing day, in particular, M. paratuberculosis appeared to
      have been present in greater abundance in the source raw milk (evidenced by more
      culture positives and stronger PCR signals), and on this occasion, surviving M.
      paratuberculosis bacteria were isolated from milk processed by all four heat
      treatments, i.e., 73 degrees C for 15 and 25 s with and without prior
      homogenization. On one other occasion, surviving M. paratuberculosis bacteria
      were isolated from an unhomogenized milk sample that had been heat treated at 73
      degrees C for 25 s. Results suggested that homogenization increases the lethality
      of subsequent heat treatment to some extent with respect to M. paratuberculosis,
      but the extended 25-s holding time at 73 degrees C was found to be no more
      effective at killing M. paratuberculosis than the standard 15-s holding time.
      This study provides clear evidence that M. paratuberculosis bacteria in naturally
      infected milk are capable of surviving commercial high-temperature, short-time
      pasteurization if they are present in raw milk in sufficient numbers.

PMID- 11823198
TI  - Conversion of L-leucine to isovaleric acid by Propionibacterium freudenreichii TL
      34 and ITGP23.
AB  - Several branched-chain volatile compounds are involved in the flavor of Swiss
      cheese. These compounds are probably produced by enzymatic conversion of branched
      chain amino acids, but the flora and the pathways involved remain hypothetical.
      Our aim was to determine the ability of Propionibacterium freudenreichii, which
      is one of the main components of the secondary flora of Swiss cheese, to produce
      flavor compounds during leucine catabolism. Cell extracts and resting cells of
      two strains were incubated in the presence of L-leucine, alpha-ketoglutaric acid,
      and cofactors, and the metabolites produced were determined by high-performance
      liquid chromatography and gas chromatography. The first step of leucine
      catabolism was a transamination that produced alpha-ketoisocaproic acid, which
      was enzymatically converted to isovaleric acid. Both reactions were faster at pH
      8.0 than at acidic pHs. Cell extracts catalyzed only the transamination step
      under our experimental conditions. Small amounts of 3-methylbutanol were also
      produced by resting cells, but neither 3-methylbutanal noralpha-hydroxyisocaproic
      acid was detected. L-Isoleucine and L-valine were also converted to the
      corresponding acids and alcohols. Isovaleric acid was produced by both strains
      during growth in a complex medium, even under conditions simulating Swiss cheese
      conditions (2.1% NaCl, pH 5.4, 24 degrees C). Our results show that P.
      frendenreichii could play a significant role in the formation of isovaleric acid
      during ripening.

PMID- 11823199
TI  - Expression of ActA, Ami, InlB, and listeriolysin O in Listeria monocytogenes of
      human and food origin.
AB  - Expression of proteins involved in the adhesion of Listeria monocytogenes to
      mammalian cells or in the intracellular life cycle of this bacterium, including
      listeriolysin O (LLO), ActA, Ami, and InlB, was used to compare two populations
      of L. monocytogenes strains. One of the populations comprised 300 clinical
      strains, and the other comprised 150 food strains. All strains expressed LLO,
      InlB, and ActA. No polymorphism was observed for LLO and InlB. Ami was detected
      in 283 of 300 human strains and in 149 of 150 food strains. The strains in which
      Ami was not detected were serovar 4b strains. Based on the molecular weights of
      the proteins detected, the strains were divided into two groups with Ami (groups
      Ami1 [75% of the strains] and Ami2 [21%]) and into four groups with ActA (groups
      ActA1 [52% of the strains], ActA2 [18%], ActA3 [30%], and ActA4 [one strain
      isolated from food]). Logistic regression showed that food strains were more
      likely to belong to group ActA3 than human strains (odds ratio [OR] = 2.90; P = 1
      x 10(-4)). Of the strains isolated from patients with non-pregnancy-related cases
      of listeriosis, bacteremia was predominantly associated with group Ami1 strains
      (OR = 1.89; P = 1 x 10(-2)) and central nervous system infections were associated
      with group ActA2 strains (OR = 3.04; P = 1 x 10(-3)) and group ActA3 strains (OR
      = 3.91; P = 1 x 10(-3)).

PMID- 11823201
TI  - Molecular characterization and substrate specificity of nitrobenzene dioxygenase
      from Comamonas sp. strain JS765.
AB  - Comamonas sp. strain JS765 can grow with nitrobenzene as the sole source of
      carbon, nitrogen, and energy. We report here the sequence of the genes encoding
      nitrobenzene dioxygenase (NBDO), which catalyzes the first step in the
      degradation of nitrobenzene by strain JS765. The components of NBDO were
      designated Reductase(NBZ), Ferredoxin(NBZ), Oxygenase(NBZalpha), and
      Oxygenase(NBZbeta), with the gene designations nbzAa, nbzAb, nbzAc, and nbzAd,
      respectively. Sequence analysis showed that the components of NBDO have a high
      level of homology with the naphthalene family of Rieske nonheme iron oxygenases,
      in particular, 2-nitrotoluene dioxygenase from Pseudomonas sp. strain JS42. The
      enzyme oxidizes a wide range of substrates, and relative reaction rates with
      partially purified Oxygenase(NBZ) revealed a preference for 3-nitrotoluene, which
      was shown to be a growth substrate for JS765. NBDO is the first member of the
      naphthalene family of Rieske nonheme iron oxygenases reported to oxidize all of
      the isomers of mono- and dinitrotoluenes with the concomitant release of nitrite.

PMID- 11823200
TI  - Proteolysis by sourdough lactic acid bacteria: effects on wheat flour protein
      fractions and gliadin peptides involved in human cereal intolerance.
AB  - Sourdough lactic acid bacteria were preliminarily screened for proteolytic
      activity by using a digest of albumin and globulin polypeptides as a substrate.
      Based on their hydrolysis profile patterns, Lactobacillus alimentarius 15M,
      Lactobacillus brevis 14G, Lactobacillus sanfranciscensis 7A, and Lactobacillus
      hilgardii 51B were selected and used in sourdough fermentation. A fractionated
      method of protein extraction and subsequent two-dimensional electrophoresis were
      used to estimate proteolysis in sourdoughs. Compared to a chemically acidified
      (pH 4.4) dough, 37 to 42 polypeptides, distributed over a wide range of pIs and
      molecular masses, were hydrolyzed by L. alimentarius 15M, L. brevis 14G, and L.
      sanfranciscensis 7A. Albumin, globulin, and gliadin fractions were hydrolyzed,
      while glutenins were not degraded. The concentrations of free amino acids,
      especially proline and glutamic and aspartic acids, also increased in sourdoughs.
      Compared to the chemically acidified dough, proteolysis by lactobacilli
      positively influenced the softening of the dough during fermentation, as
      determined by rheological analyses. Enzyme preparations of the selected
      lactobacilli which contained proteinase or peptidase enzymes showed hydrolysis of
      the 31-43 fragment of A-gliadin, a toxic peptide for celiac patients. A toxic
      peptic-tryptic (PT) digest of gliadins was used for in vitro agglutination tests
      on K 562 (S) subclone cells of human myelagenous leukemia origin. The lowest
      concentration of PT digest that agglutinated 100% of the total cells was 0.218
      g/liter. Hydrolysis of the PT digest by proteolytic enzymes of L. alimentarius
      15M and L. brevis 14G completely prevented agglutination of the K 562 (S) cells
      by the PT digest at a concentration of 0.875 g/liter. Considerable inhibitory
      effects by other strains and at higher concentrations of the PT digest were also
      found. The mixture of peptides produced by enzyme preparations of selected
      lactobacilli showed a decreased agglutination of K 562 (S) cells with respect to
      the whole 31-43 fragment of A-gliadin.

PMID- 11823202
TI  - Tetrachloroethene dehalorespiration and growth of Desulfitobacterium frappieri
      TCE1 in strict dependence on the activity of Desulfovibrio fructosivorans.
AB  - Tetrachloroethene (PCE) dehalorespiration was investigated in a continuous
      coculture of the sulfate-reducing bacterium Desulfovibrio fructosivorans and the
      dehalorespiring Desulfitobacterium frappieri TCE1 at different sulfate
      concentrations and in the absence of sulfate. Fructose (2.5 mM) was the single
      electron donor, which could be used only by the sulfate reducer. With 2.5 mM
      sulfate, the dehalogenating strain was outnumbered by the sulfate-reducing
      bacterium, sulfate reduction was the dominating process, and only trace amounts
      of PCE were dehalogenated by strain TCE1. With 1 mM sulfate in the medium,
      complete sulfate reduction and complete PCE dehalogenation to cis-dichloroethene
      (cis-DCE) occurred. In the absence of sulfate, PCE was also completely
      dehalogenated to cis-DCE, and the population size of strain TCE1 increased
      significantly. The results presented here describe for the first time
      dehalogenation of PCE by a dehalorespiring anaerobe in strict dependence on the
      activity of a sulfate-reducing bacterium with a substrate that is exclusively
      used by the sulfate reducer. This interaction was studied under strictly
      controlled and quantifiable conditions in continuous culture and shown to depend
      on interspecies hydrogen transfer under sulfate-depleted conditions. Interspecies
      hydrogen transfer was demonstrated by direct H(2) measurements of the gas phase
      and by the production of methane after the addition of a third organism,
      Methanobacterium formicicum.

PMID- 11823203
TI  - Identification and characterization of pathogenic Aeromonas veronii biovar sobria
      associated with epizootic ulcerative syndrome in fish in Bangladesh.
AB  - Sparse information is available on the virulence factors of Aeromonas strains
      isolated from diseased fish, from the environment, and from humans. In the
      present study, 52 Aeromonas isolates obtained from epizootic ulcerative syndrome
      (EUS) lesions in fish, from the aquatic environment, and from children with
      diarrhea in Bangladesh were identified by biochemical phenotyping (i.e.,
      PhenePlate [PhP] typing) and DNA fingerprinting and then characterized with
      respect to certain putative virulence factors. The isolates from the fish
      exhibiting EUS symptoms were identified to be Aeromonas veronii biovar sobria by
      fatty acid methyl ester analysis and amplified fragment length polymorphism
      fingerprinting. Biochemical phenotyping revealed that all EUS-associated isolates
      belonged to a unique phenotype which was not identified among more than 1,600
      environmental and diarrheal isolates in a previously collected database of PhP
      types of Bangladeshi Aeromonas isolates. The 52 Aeromonas isolates were
      investigated for the production of hemolysin and cytotoxin; for hemagglutination
      with erythrocytes from fish, human, and rabbit sources; for the presence of a
      cytolytic enterotoxin gene; and for adhesion to and invasion into fish cell
      lines. All of the EUS isolates produced all of the virulence factors
      investigated, as did also some of the environmental isolates, but the isolates
      from EUS were unique in their ability to agglutinate fish erythrocytes. Our
      results suggest that a clonal group of A. veronii biovar sobria is associated
      with, and may be a causative agent of, EUS in fish in Bangladesh.

PMID- 11823204
TI  - Characterization of Wolbachia host cell range via the in vitro establishment of
      infections.
AB  - Maternally transmitted bacteria of the genus Wolbachia are obligate,
      intracellular symbionts that are frequently found in insects and cause a diverse
      array of reproductive manipulations, including cytoplasmic incompatibility, male
      killing, parthenogenesis, and feminization. Despite the existence of a broad
      range of scientific interest, many aspects of Wolbachia research have been
      limited to laboratories with insect-rearing facilities. The inability to culture
      these bacteria outside of the invertebrate host has also led to the existing bias
      of Wolbachia research toward infections that occur in host insects that are
      easily reared. Here, we demonstrate that Wolbachia infections can be simply
      established, stably maintained, and cryogenically stored in vitro using standard
      tissue culture techniques. We have examined Wolbachia host range by introducing
      different Wolbachia types into a single tissue culture. The results show that an
      Aedes albopictus (Diptera: Culicidae) cell line can support five different
      Wolbachia infection types derived from Drosophila simulans (Diptera:
      Drosophilidae), Culex pipiens (Culicidae), and Cadra cautella (Lepidoptera:
      Phycitidae). These bacterial types include infection types that have been
      assigned to two of the major Wolbachia clades. As an additional examination of
      Wolbachia host cell range, we demonstrated that a Wolbachia strain from D.
      simulans could be established in host insect cell lines derived from A.
      albopictus, Spodoptera frugiperda (Lepidoptera: Noctuidae), and Drosophila
      melanogaster. These results will facilitate the development of a Wolbachia stock
      center, permitting novel approaches for the study of Wolbachia infections and
      encouraging Wolbachia research in additional laboratories.

PMID- 11823205
TI  - Comparison of fluorescently labeled oligonucleotide and polynucleotide probes for
      the detection of pelagic marine bacteria and archaea.
AB  - We compared the detection of bacteria and archaea in the coastal North Sea and at
      Monterey Bay, Calif., after fluorescence in situ hybridization (FISH) either with
      rRNA-targeted oligonucleotide probes monolabeled with the cyanin dye Cy3
      (oligoFISH) or with fluorescein-labeled polyribonucleotide probes (polyFISH).
      During an annual cycle in German Bight surface waters, the percentages of
      bacteria visualized by polyFISH (annual mean, 77% of total counts) were
      significantly higher than those detected by oligoFISH (53%). The fraction of
      total bacteria visualized by oligoFISH declined during winter, whereas cell
      numbers determined by polyFISH remained constant throughout the year. Depth
      profiles from Monterey Bay showed large differences in the fraction of bacterial
      cells visualized by polyFISH and oligoFISH in the deeper water layers
      irrespective of the season. Image-analyzed microscopy indicated that the superior
      detection of cells by polyFISH with fluorescein-labeled probes in
      bacterioplankton samples was less a consequence of higher absolute fluorescence
      intensities but was rather related to quasi-linear bleaching dynamics and to a
      higher signal-to-background ratio. The relative abundances of archaea in North
      Sea and Monterey Bay spring samples as determined by oligoFISH were on average
      higher than those determined by polyFISH. However, simultaneous hybridizations
      with oligonucleotide probes for bacteria and archaea suggested that the oligoFISH
      probe ARCH915 unspecifically stained a population of bacteria. Using either FISH
      technique, blooms of archaea were observed in North Sea surface waters during the
      spring and summer months. Marine group II archaea (Euryarchaeota) reached >30% of
      total picoplankton abundances, as determined by polyFISH. We suggest that studies
      of pelagic microbial community structure using oligoFISH with monolabeled probes
      should focus on environments that yield detections > or =70% of total cell
      counts, e.g., coastal surface waters during spring and summer.

PMID- 11823206
TI  - Characterization of the norB gene, encoding nitric oxide reductase, in the
      nondenitrifying cyanobacterium Synechocystis sp. strain PCC6803.
AB  - A norB gene encoding a putative nitric oxide reductase is present in the genome
      of the nondenitrifying cyanobacterium Synechocystis sp. strain PCC6803. The gene
      product belongs to the quinol-oxidizing single-subunit class of nitric oxide
      reductases, discovered recently in the denitrifier Ralstonia eutropha.
      Heterologous complementation of a nitric oxide reductase-negative mutant of R.
      eutropha with norB from Synechocystis restored nitric oxide reductase activity.
      With reduced menadione as the electron donor, an enzymatic activity of 101 nmol
      of NO per min per mg of protein was obtained with membrane fractions of
      Synechocystis wild-type cells. Virtually no nitric oxide reductase activity was
      present in a norB-negative mutant of Synechocystis. Growing cells of this mutant
      are more sensitive toward NO than wild-type cells, indicating that the presence
      of a nitric oxide reductase is beneficial for Synechocystis when the cells are
      exposed to NO. Transcriptional fusions with the chloramphenicol acetyltransferase
      reporter gene were constructed to monitor norB expression in Synechocystis.
      Transcription of norB was not enhanced by the addition of the NO-generating agent
      sodium nitroprusside.

PMID- 11823209
TI  - 16S ribosomal DNA-based analysis of bacterial diversity in purified water used in
      pharmaceutical manufacturing processes by PCR and denaturing gradient gel
      electrophoresis.
AB  - The bacterial community in partially purified water, which is prepared by ion
      exchange from tap water and is used in pharmaceutical manufacturing processes,
      was analyzed by denaturing gradient gel electrophoresis (DGGE). 16S ribosomal DNA
      fragments, including V6, -7, and -8 regions, were amplified with universal
      primers and analyzed by DGGE. The bacterial diversity in purified water
      determined by PCR-DGGE banding patterns was significantly lower than that of
      other aquatic environments. The bacterial populations with esterase activity
      sorted by flow cytometry and isolated on soybean casein digest (SCD) and R2A
      media were also analyzed by DGGE. The dominant bacterium in purified water
      possessed esterase activity but could not be detected on SCD or R2A media. DNA
      sequence analysis of the main bands on the DGGE gel revealed that culturable
      bacteria on these media were Bradyrhizobium sp., Xanthomonas sp., and
      Stenotrophomonas sp., while the dominant bacterium was not closely related to
      previously characterized bacteria. These data suggest the importance of culture
      independent methods of quality control for pharmaceutical water.

PMID- 11823208
TI  - Chemostat approach for the directed evolution of biodesulfurization gain-of
      function mutants.
AB  - Chemostat enrichment is a classical microbiological method that is well suited
      for use in directed-evolution strategies. We used a two-phase sulfur-limited
      chemostat to select for gain-of-function mutants with mutations in the
      biodesulfurization (Dsz) system of Rhodococcus erythropolis IGTS8, enriching for
      growth in the presence of organosulfur compounds that could not support growth of
      the wild-type strain. Mutations arose that allowed growth with octyl sulfide and
      5-methylbenzothiophene as sole sulfur sources. An isolate from the evolved
      chemostat population was genetically characterized and found to contain mutations
      in two genes, dszA and dszC. A transversion (G to T) in dszC codon 261 resulted
      in a V261F mutation that was determined to be responsible for the 5
      methylbenzothiophene gain-of-function phenotype. By using a modified RACHITT
      (random chimeragenesis on transient templates) method, mutant DszC proteins
      containing all possible amino acids at that position were generated, and this
      mutant set was assayed for the ability to metabolize 5-methylbenzothiophene,
      alkyl thiophenes, and dibenzothiophene. No mutant with further improvements in
      these catalytic activities was identified, but several clones lost all activity,
      confirming the importance of codon 261 for enzyme activity.

PMID- 11823207
TI  - Culture-independent analysis of gut bacteria: the pig gastrointestinal tract
      microbiota revisited.
AB  - The phylogenetic diversity of the intestinal bacterial community in pigs was
      studied by comparative 16S ribosomal DNA (rDNA) sequence analysis. Samples were
      collected from a total of 24 pigs representing a variety of diets, ages, and herd
      health status. A library comprising 4,270 cloned 16S rDNA sequences obtained
      directly by PCR from 52 samples of either the ileum, the cecum, or the colon was
      constructed. In total, 375 phylotypes were identified using a 97% similarity
      criterion. Three hundred nine of the phylotypes (83%) had a <97% sequence
      similarity to any sequences in the database and may represent yet-uncharacterized
      bacterial genera or species. The phylotypes were affiliated with 13 major
      phylogenetic lineages. Three hundred four phylotypes (81%) belonged to the low
      G+C gram-positive division, and 42 phylotypes (11.2%) were affiliated with the
      Bacteroides and Prevotella group. Four clusters of phylotypes branching off
      deeply within the low-G+C gram-positive bacteria and one in the Mycoplasma
      without any cultured representatives were found. The coverage of all the samples
      was 97.2%. The relative abundance of the clones approximated a lognormal
      distribution; however, the phylotypes detected and their abundance varied between
      two libraries from the same sample. The results document that the intestinal
      microbial community is very complex and that the majority of the bacterial
      species colonizing the gastrointestinal tract in pigs have not been
      characterized.

PMID- 11823210
TI  - Efficient insertion mutagenesis strategy for bacterial genomes involving
      electroporation of in vitro-assembled DNA transposition complexes of
      bacteriophage mu.
AB  - An efficient insertion mutagenesis strategy for bacterial genomes based on the
      phage Mu DNA transposition reaction was developed. Incubation of MuA transposase
      protein with artificial mini-Mu transposon DNA in the absence of divalent cations
      in vitro resulted in stable but inactive Mu DNA transposition complexes, or
      transpososomes. Following delivery into bacterial cells by electroporation, the
      complexes were activated for DNA transposition chemistry after encountering
      divalent metal ions within the cells. Mini-Mu transposons were integrated into
      bacterial chromosomes with efficiencies ranging from 10(4) to 10(6) CFU/microg of
      input transposon DNA in the four species tested, i.e., Escherichia coli,
      Salmonella enterica serovar Typhimurium, Erwinia carotovora, and Yersinia
      enterocolitica. Efficiency of integration was influenced mostly by the competence
      status of a given strain or batch of bacteria. An accurate 5-bp target site
      duplication flanking the transposon, a hallmark of Mu transposition, was
      generated upon mini-Mu integration into the genome, indicating that a genuine DNA
      transposition reaction was reproduced within the cells of the bacteria studied.
      This insertion mutagenesis strategy for microbial genomes may be applicable to a
      variety of organisms provided that a means to introduce DNA into their cells is
      available.

PMID- 11823211
TI  - Impact of transport crate reuse and of catching and processing on Campylobacter
      and Salmonella contamination of broiler chickens.
AB  - The influence of transport, catching, and processing on contamination of broiler
      chickens with Salmonella and Campylobacter was investigated. Transport crates
      were reused with high frequency and were often still contaminated with Salmonella
      and Campylobacter when they arrived at the farm despite the fact that they were
      washed at the factory, and thus they were a potential route of infection. These
      organisms contaminated the feathers of previously Campylobacter- and Salmonella
      negative birds going to the processing plant and were isolated from processed
      carcasses, albeit at a low frequency. The Campylobacter types which were the
      predominant organisms on the live birds when they arrived at the processing plant
      were not necessarily the types that were most frequently isolated from processed
      carcasses. This finding may reflect cross-contamination that occurred during
      processing or differences in the tolerance of the strains to the hostile
      environments that the bacteria experienced. The process of catching and putting
      the birds in crates significantly increased the chance of contamination with
      Campylobacter (P < 0.001).

PMID- 11823213
TI  - Listeria monocytogenes LO28: surface physicochemical properties and ability to
      form biofilms at different temperatures and growth phases.
AB  - The surface physicochemical properties of Listeria monocytogenes LO28 under
      different conditions (temperature and growth phase) were determined by use of
      microelectrophoresis and microbial adhesion to solvents. The effect of these
      parameters on adhesion and biofilm formation by L. monocytogenes LO28 on
      hydrophilic (stainless steel) and hydrophobic (polytetrafluoroethylene [PTFE])
      surfaces was assessed. The bacterial cells were always negatively charged and
      possessed hydrophilic surface properties, which were negatively correlated with
      growth temperature. The colonization of the two surfaces, monitored by scanning
      electron microscopy, epifluorescence microscopy, and cell enumeration, showed
      that the strain had a great capacity to colonize both surfaces whatever the
      incubation temperature. However, biofilm formation was faster on the hydrophilic
      substratum. After 5 days at 37 or 20 degrees C, the biofilm structure was
      composed of aggregates with a three-dimensional shape, but significant detachment
      took place on PTFE at 37 degrees C. At 8 degrees C, only a bacterial monolayer
      was visible on stainless steel, while no growth was observed on PTFE. The growth
      phase of bacteria used to inoculate surfaces had a significant effect only in
      some cases during the first steps of biofilm formation. The surface
      physicochemical properties of the strain are correlated with adhesion and surface
      colonization.

PMID- 11823212
TI  - Identification, characterization, and expression of a second, bicistronic, operon
      involved in the production of lactocin S in Lactobacillus sakei L45.
AB  - Through the analysis of spontaneous insertion mutants of Lactobacillus sakei L45,
      a second operon involved in lactocin S production was identified and
      characterized. The new, bicistronic unit, termed lasXY, is situated immediately
      upstream of the previously characterized nine-open reading frame (ORF) lactocin S
      operon (lasA-W) and is transcribed in the opposite direction. The proximal of the
      two newly identified genes, lasX, specifies a 285-residue protein that is similar
      to a group of proteins with reported gene regulation functions in gram-positive
      bacteria. It was demonstrated that the lasX mutants have a strongly reduced level
      of lasA and lasA-W mRNA, thus indicating the likely cause of the Bac(-) phenotype
      of these mutants. The second ORF in the operon, lasY, specifies a 300-residue ABC
      transporter homolog, the function of which is currently obscure. Transcription
      initiation mapping of the lasXY operon demonstrates that the two lactocin S
      promoters overlap such that both transcripts initiate within the -35 region of
      the oppositely oriented promoter. This organization of promoters is unique among
      this group of regulons and may constitute a modulatory site in the proposed LasX
      dependent expression of lasA and downstream genes.

PMID- 11823214
TI  - Horizontal transfer of the plant virulence gene, nec1, and flanking sequences
      among genetically distinct Streptomyces strains in the Diastatochromogenes
      cluster.
AB  - Evidence for the horizontal transfer of a pathogenicity island (PAI) carrying the
      virulence gene nec1 and flanking sequences among Streptomyces strains in the
      Diastatochromogenes cluster is presented. Plant-pathogenic, thaxtomin-producing
      Streptomyces strains, previously classified as S. scabiei based on the
      conventionally used phenotypic characteristics, were found to be genetically
      distinct from the type strain of S. scabiei based on DNA relatedness and 16S rDNA
      sequence analysis. Pairwise DNA-DNA hybridizations between some of these strains
      and the S. scabiei type strain were as low as 36%, a value much below what is
      conventionally accepted for species identity (70%). The sequence of the nec1
      gene, however, was identical in all the S. scabiei and S. scabiei-like strains
      tested, irrespective of their DNA relatedness to the type strain of S. scabiei,
      their geographic origin, or the isolation host. Furthermore, a 26-kb DNA fragment
      including and flanking nec1 was also conserved among these strains based on
      restriction and Southern analyses. These data indicate that the etiology of
      potato scab is more complex than previously recognized; this result has important
      implications for potato scab management strategies. Previous research has
      suggested that horizontal transfer of a PAI was the mechanism for evolution of
      pathogenicity in S. acidiscabies and S. turgidiscabies, species that lie outside
      of the Diastatochromogenes cluster. Data presented here support this model and
      indicate that PAI transfer also has occurred frequently in species closely
      related to S. scabiei.

PMID- 11823215
TI  - Molecular analyses of the natural transformation machinery and identification of
      pilus structures in the extremely thermophilic bacterium Thermus thermophilus
      strain HB27.
AB  - Thermus thermophilus HB27, an extremely thermophilic bacterium, exhibits high
      competence for natural transformation. To identify genes of the natural
      transformation machinery of T. thermophilus HB27, we performed homology searches
      in the partially completed T. thermophilus genomic sequence for conserved
      competence genes. These analyses resulted in the detection of 28 open reading
      frames (ORFs) exhibiting significant similarities to known competence proteins of
      gram-negative and gram-positive bacteria. Disruption of 15 selected potential
      competence genes led to the identification of 8 noncompetent mutants and one
      transformation-deficient mutant with a 100-fold reduced transformation frequency.
      One competence protein is similar to DprA of Haemophilus influenzae, seven are
      similar to type IV pilus proteins of Pseudomonas aeruginosa or Neisseria
      gonorrhoeae (PilM, PilN, PilO, PilQ, PilF, PilC, PilD), and another deduced
      protein (PilW) is similar to a protein of unknown function in Deinococcus
      radiodurans R1. Analysis of the piliation phenotype of T. thermophilus HB27
      revealed the presence of single pilus structures on the surface of the wild-type
      cells, whereas the noncompetent pil mutants of Thermus, with the exception of the
      pilF mutant, were devoid of pilus structures. These results suggest that pili and
      natural transformation in T. thermophilus HB27 are functionally linked.

PMID- 11823216
TI  - Frequency of bacteriocin resistance development and associated fitness costs in
      Listeria monocytogenes.
AB  - Bacteriocin-producing starter cultures have been suggested as natural food
      preservatives; however, development of resistance in the target organism is a
      major concern. We investigated the development of resistance in Listeria
      monocytogenes to the two major bacteriocins pediocin PA-1 and nisin A, with a
      focus on the variations between strains and the influence of environmental
      conditions. While considerable strain-specific variations in the frequency of
      resistance development and associated fitness costs were observed, the influence
      of environmental stress seemed to be bacteriocin specific. Pediocin resistance
      frequencies were determined for 20 strains and were in most cases ca. 10(-6).
      However, two strains with intermediate pediocin sensitivity had 100-fold-higher
      pediocin resistance frequencies. Nisin resistance frequencies (14 strains) were
      in the range of 10(-7) to 10(-2). Strains with intermediate nisin sensitivity
      were among those with the highest frequencies. Environmental stress in the form
      of low temperature (10 degrees C), reduced pH (5.5), or the presence of NaCl
      (6.5%) did not influence the frequency of pediocin resistance development; in
      contrast, the nisin resistance frequency was considerably reduced (<5 x 10(-8)).
      Pediocin resistance in all spontaneous mutants was very stable, but the stability
      of nisin resistance varied. Pediocin-resistant mutants had fitness costs in the
      form of reduction down to 44% of the maximum specific growth rate of the wild
      type strain. Nisin-resistant mutants had fewer and less-pronounced growth rate
      reductions. The fitness costs were not increased upon applying environmental
      stress (5 degrees C, 6.5% NaCl, or pH 5.5), indicating that the bacteriocin
      resistant mutants were not more stress sensitive than the wild-type strains. In a
      saveloy-type meat model at 5 degrees C, however, the growth differences seemed to
      be negligible. The applicational perspectives of the results are discussed.

PMID- 11823217
TI  - Genomic diversity within the genus Pediococcus as revealed by randomly amplified
      polymorphic DNA PCR and pulsed-field gel electrophoresis.
AB  - The genomic diversity of 33 previously assigned strains from six species within
      the genus Pediococcus was assessed by randomly amplified polymorphic DNA (RAPD)
      PCR and pulsed-field-gel electrophoresis (PFGE). The RAPD PCR patterns produced
      by two separate random primers, termed P1 (ACGCGCCCT) and P2 (ATGTAACGCC), were
      compared by the Pearson correlation coefficient and the unweighted pair group
      method with arithmetic averages clustering algorithm. Pattern variations between
      repeat samples set a strain discrimination threshold of less than 70% similarity.
      P1 and P2 primers alone and in combination produced 14, 21, and 28 distinct
      patterns, respectively. When each strain was assigned with a type strain with
      which it shared the highest level of similarity, both primers grouped 17 of the
      27 strains to their proposed species. PFGE following genomic digestion with the
      restriction enzymes ApaI, NotI, and AscI produced 30, 32, and 28 distinct
      macrorestriction patterns, respectively. Specific DNA fragments within the NotI
      and AscI macrorestriction patterns for each strain were observed that allowed 27
      of the 33 strains to be assigned to their proposed species. For example,
      following digestion with AscI, all Pediococcus parvulus strains were
      characterized by two DNA fragments, one of approximately 220 kb and another
      between 700 and 800 kb. The exceptions correlated with those observed with both
      RAPD PCR primers and included three P. damnosus and two P. pentosaceus strains
      that grew at temperatures regarded as nonpermissive for their proposed species
      but not for those with which they grouped.

PMID- 11823218
TI  - Osmotically regulated synthesis of the compatible solute ectoine in Bacillus
      pasteurii and related Bacillus spp.
AB  - By using natural-abundance (13)C-nuclear magnetic resonance spectroscopy and high
      performance liquid chromatography (HPLC) analysis we have investigated the types
      of compatible solutes that are synthesized de novo in a variety of Bacillus
      species under high-osmolality growth conditions. Five different patterns of
      compatible solute production were found among the 13 Bacillus species we studied.
      Bacillus subtilis, B. licheniformis, and B. megaterium produced proline; B.
      cereus, B. circulans, B. thuringiensis, Paenibacillus polymyxa, and
      Aneurinibacillus aneurinilyticus synthesized glutamate; B. alcalophilus, B.
      psychrophilus, and B. pasteurii synthesized ectoine; and Salibacillus (formerly
      Bacillus) salexigens produced both ectoine and hydroxyectoine, whereas
      Virgibacillus (formerly Bacillus) pantothenticus synthesized both ectoine and
      proline. Hence, the ability to produce the tetrahydropyrimidine ectoine under
      hyperosmotic growth conditions is widespread within the genus Bacillus and
      closely related taxa. To study ectoine biosynthesis within the group of Bacillus
      species in greater detail, we focused on B. pasteurii. We cloned and sequenced
      its ectoine biosynthetic genes (ectABC). The ectABC genes encode the
      diaminobutyric acid acetyltransferase (EctA), the diaminobutyric acid
      aminotransferase (EctB), and the ectoine synthase (EctC). Together these proteins
      constitute the ectoine biosynthetic pathway, and their heterologous expression in
      B. subtilis led to the production of ectoine. Northern blot analysis demonstrated
      that the ectABC genes are genetically organized as an operon whose expression is
      strongly enhanced when the osmolality of the growth medium is raised. Primer
      extension analysis allowed us to pinpoint the osmoregulated promoter of the B.
      pasteurii ectABC gene cluster. HPLC analysis of osmotically challenged B.
      pasteurii cells revealed that ectoine production within this bacterium is finely
      tuned and closely correlated with the osmolality of the growth medium. These
      observations together with the osmotic control of ectABC transcription suggest
      that the de novo synthesis of ectoine is an important facet in the cellular
      adaptation of B. pasteurii to high-osmolarity surroundings.

PMID- 11823219
TI  - Enhanced exopolysaccharide production by metabolic engineering of Streptococcus
      thermophilus.
AB  - It is possible that the low levels of production of exopolysaccharides (EPSs) by
      lactic acid bacteria could be improved by altering the levels of enzymes in the
      central metabolism that influence the production of precursor nucleotide sugars.
      To test this hypothesis, we identified and cloned the galU gene, which codes for
      UDP glucose pyrophosphorylase (GalU) in Streptococcus thermophilus LY03.
      Homologous overexpression of the gene led to a 10-fold increase in GalU activity
      but did not have any effect on the EPS yield when lactose was the carbon source.
      However, when galU was overexpressed in combination with pgmA, which encodes
      phosphoglucomutase (PGM), the EPS yield increased from 0.17 to 0.31 g/mol of
      carbon from lactose. A galactose-fermenting LY03 mutant (Gal(+)) with increased
      activities of the Leloir enzymes was also found to have a higher EPS yield (0.24
      g/mol of carbon) than the parent strain. The EPS yield was further improved to
      0.27 g/mol of carbon by overexpressing galU in this strain. However, the highest
      EPS yield, 0.36 g/mol of carbon, was obtained when pgmA was knocked out in the
      Gal(+) strain. Measurements of the levels of intracellular metabolites in the
      cultures revealed that the Gal(+) strains had considerably higher glucose 1
      phosphate levels than the other strains, and the strain lacking PGM activity had
      threefold-higher levels of glucose 1-phosphate than the other Gal(+) strains.
      These results show that it is possible to increase EPS production by altering the
      levels of enzymes in the central carbohydrate metabolism.

PMID- 11823220
TI  - Use of a marker organism to model the spread of central nervous system tissue in
      cattle and the abattoir environment during commercial stunning and carcass
      dressing.
AB  - Due to concerns about a link between variant Creutzfeldt-Jakob disease in humans
      and similar prion protein-induced disease in cattle, i.e., bovine spongiform
      encephalopathy (BSE), strict controls are in place to exclude BSE-positive
      animals and/or specified risk materials including bovine central nervous system
      (CNS) tissue from the human food chain. However, current slaughter practice,
      using captive bolt guns, may induce disruption of brain tissues and mobilize CNS
      tissues into the bovine circulatory system, leading to the dispersion of CNS
      tissues (including prion proteins) throughout the derived carcass. This project
      used a marker (antibiotic-resistant) strain of Pseudomonas fluorescens to model
      the effects of commercial captive bolt stunning procedures on the movement of
      mobilized CNS material within slaughtered animals and the abattoir environment.
      The marker organism, introduced by injection through the bolt entry aperture or
      directly using a cartridge-fired captive bolt, was detected in the slaughter
      environment immediately after stunning and in the abattoir environment at each
      subsequent stage of the slaughter-dressing process. The marker organism was also
      detected on the hands of operatives; on slaughter equipment; and in samples of
      blood, organs, and musculature of inoculated animals. There were no significant
      differences between the results obtained by the two inoculation methods (P <
      0.05). This study demonstrates that material present in, or introduced into, the
      CNS of cattle during commercial captive bolt stunning may become widely dispersed
      across the many animate and inanimate elements of the slaughter-dressing
      environment and within derived carcasses including meat entering the human food
      chain.

PMID- 11823221
TI  - Optimization of reverse transcriptase PCR to detect viable Shiga-toxin-producing
      Escherichia coli.
AB  - The ability of reverse transcriptase PCR (RT-PCR) to detect viable Shiga-toxin
      producing Escherichia coli (STEC) was investigated. Four primer sets, each
      targeting a specific region in the slt-II operon, were evaluated for their
      stringency and specificity for slt-II mRNA. STEC were evaluated for toxin
      expression under various conditions, including cell growth phase, growth medium,
      incubation temperature, and aeration. Following primer optimization, STEC were
      inoculated into Trypticase soy broth and cooked ground beef enrichments. Cells
      were harvested and RNA or DNA was extracted at 4, 8, 12, and 24 h. RT-PCR or PCR
      was conducted, and the products were visualized by gel electrophoresis and by
      Southern blots. mRNA targets were detected in 12-h cooked ground meat enrichments
      with an initial inoculum of 1 CFU/g. These results indicate that RT-PCR of E.
      coli slt-II mRNA is useful for detection of viable STEC in ground beef.

PMID- 11823222
TI  - Identification of a bacterium that specifically catalyzes the reductive
      dechlorination of polychlorinated biphenyls with doubly flanked chlorines.
AB  - A microorganism whose growth is linked to the dechlorination of polychlorinated
      biphenyls (PCBs) with doubly flanked chlorines was identified. Identification was
      made by reductive analysis of community 16S ribosomal DNA (rDNA) sequences from a
      culture enriched in the presence of 2,3,4,5-tetrachlorobiphenyl (2,3,4,5-CB),
      which was dechlorinated at the para position. Denaturing gradient gel
      electrophoresis (DGGE) analysis of total 16S rDNA extracted from the culture led
      to identification of three operational taxonomic units (OTUs 1, 2, and 3). OTU 1
      was always detected when 2,3,4,5-CB or other congeners with doubly flanked
      chlorines were present and dechlorinated. Only OTUs 2 and 3 were detected in the
      absence of PCBs and when other PCBs (i.e., PCBs lacking doubly flanked chlorines)
      were not dechlorinated. Partial sequences of OTUs 2 and 3 exhibited 98.2%
      similarity to the sequence of "Desulfovibrio caledoniensis" (accession no.
      DCU53465). A sulfate-reducing vibrio isolated from the culture generated OTUs 2
      and 3. This organism could not dechlorinate 2,3,4,5-CB. From these results we
      concluded that OTU 1 represents the dechlorinating bacterium growing in a
      coculture with a Desulfovibrio sp. The 16S rDNA sequence of OTU 1 is most similar
      to the 16S rDNA sequence of bacterium o-17 (89% similarity), an ortho-PCB
      dechlorinating bacterium. The PCB dechlorinator, designated bacterium DF-1,
      reductively dechlorinates congeners with doubly flanked chlorines when it is
      supplied with formate or H(2)-CO(2) (80:20).

PMID- 11823223
TI  - Characterization of glycine betaine porter I from Listeria monocytogenes and its
      roles in salt and chill tolerance.
AB  - Listeria monocytogenes is a pathogenic bacterium that can grow at low
      temperatures and elevated osmolarity. The organism survives these stresses by the
      intracellular accumulation of osmolytes: low-molecular-weight organic compounds
      which exert a counterbalancing force. The primary osmolyte in L. monocytogenes is
      glycine betaine, which is accumulated from the environment via two transport
      systems: glycine betaine porter I, an Na(+)-glycine betaine symporter; and
      glycine betaine porter II, an ATP-dependent transporter. The biochemical
      characteristics of glycine betaine porter I were investigated in a mutant strain
      (LTG59) lacking the ATP-dependent transporter. At 4% NaCl, glycine betaine uptake
      in LTG59 was about fivefold lower than in strain DP-L1044, which has both
      transporters, indicating that the ATP-dependent transporter is the primary means
      by which glycine betaine enters the cell. In the absence of osmotic stress, cold
      activated uptake by both transporters was most rapid between 7 and 12 degrees C,
      but a larger fraction of the total uptake was via the ATP-dependent transporter
      than was observed under salt-stressed conditions. Twelve glycine betaine analogs
      were tested for their ability to inhibit glycine betaine uptake and growth of
      stressed cultures. Carnitine, dimethylglycine, and gamma-butyrobetaine appear to
      inhibit the ATP-dependent transporter, while trigonelline and triethylglycine
      primarily inhibit glycine betaine porter I. Triethylglycine was also able to
      retard the growth of osmotically stressed L. monocytogenes grown in the presence
      of glycine betaine.

PMID- 11823224
TI  - Biodiversity of the bacterial flora on the surface of a smear cheese.
AB  - The bacteria on the surface of a farmhouse smear-ripened cheese at four stages of
      ripening (4, 16, 23, and 37 days) from inoculated (i.e., deliberately inoculated
      with Brevibacterium linens BL2) and noninoculated (not deliberately inoculated
      with B. linens BL2) cheese were investigated. The results show that, contrary to
      accepted belief, B. linens is not a significant member of the surface flora of
      smear cheese and no microbial succession of species occurred during the ripening
      of the cheeses. Of 400 isolates made, 390 were lactate-utilizing coryneforms and
      10 were coagulase-negative Staphylococcus spp. A detailed analysis of the
      coryneforms was undertaken using phenotypic analysis, molecular fingerprinting,
      chemotaxonomic techniques, and 16S rRNA gene sequencing. DNA banding profiles
      (ramdom amplified polymorphic DNA [RAPD]-PCR) of all the coryneform isolates
      showed large numbers of clusters. However, pulsed-field gel electrophoresis
      (PFGE) of the isolates from the cheeses showed that all isolates within a cluster
      and in many contiguous clusters were the same. The inoculated and noninoculated
      cheeses were dominated by single clones of novel species of Corynebacterium casei
      (50.2% of isolates), Corynebacterium mooreparkense (26% of isolates), and
      Microbacterium gubbeenense (12.8% of isolates). In addition, five of the isolates
      from the inoculated cheese were Corynebacterium flavescens. Thirty-seven strains
      were not identified but many had similar PFGE patterns, indicating that they were
      the same species. C. mooreparkense and C. casei grew at pH values below 4.9 in
      the presence of 8% NaCl, while M. gubbeenense did not grow below pH 5.8 in the
      presence of 5 to 10% NaCl. B. linens BL2 was not recovered from the inoculated
      cheese because it was inhibited by all the Staphylococcus isolates and many of
      the coryneforms. It was concluded that within a particular batch of cheese there
      was significant bacterial diversity in the microflora on the surface.

PMID- 11823225
TI  - Expression of the xylulose 5-phosphate phosphoketolase gene, xpkA, from
      Lactobacillus pentosus MD363 is induced by sugars that are fermented via the
      phosphoketolase pathway and is repressed by glucose mediated by CcpA and the
      mannose phosphoenolpyruvate phosphotransferase system.
AB  - Purification of xylulose 5-phosphate phosphoketolase (XpkA), the central enzyme
      of the phosphoketolase pathway (PKP) in lactic acid bacteria, and cloning and
      sequence analysis of the encoding gene, xpkA, from Lactobacillus pentosus MD363
      are described. xpkA encodes a 788-amino-acid protein with a calculated mass of
      88,705 Da. Expression of xpkA in Escherichia coli led to an increase in XpkA
      activity, while an xpkA knockout mutant of L. pentosus lost XpkA activity and was
      not able to grow on energy sources that are fermented via the PKP, indicating
      that xpkA encodes an enzyme with phosphoketolase activity. A database search
      revealed that there are high levels of similarity between XpkA and a
      phosphoketolase from Bifidobacterium lactis and between XpkA and a (putative)
      protein present in a number of evolutionarily distantly related organisms (up to
      54% identical residues). Expression of xpkA in L. pentosus was induced by sugars
      that are fermented via the PKP and was repressed by glucose mediated by carbon
      catabolite protein A (CcpA) and by the mannose phosphoenolpyruvate
      phosphotransferase system. Most of the residues involved in correct binding of
      the cofactor thiamine pyrophosphate (TPP) that are conserved in transketolase,
      pyruvate decarboxylase, and pyruvate oxidase were also conserved at a similar
      position in XpkA, implying that there is a similar TPP-binding fold in XpkA.

PMID- 11823226
TI  - Molecular relationship between two groups of the genus Leptospirillum and the
      finding that Leptospirillum ferriphilum sp. nov. dominates South African
      commercial biooxidation tanks that operate at 40 degrees C.
AB  - Iron-oxidizing bacteria belonging to the genus Leptospirillum are of great
      importance in continuous-flow commercial biooxidation reactors, used for
      extracting metals from minerals, that operate at 40 degrees C or less. They also
      form part of the microbial community responsible for the generation of acid mine
      drainage. More than 16 isolates of leptospirilla were included in this study, and
      they were clearly divisible into two major groups. Group I leptospirilla had G+C
      moles percent ratios within the range 49 to 52% and had three copies of rrn
      genes, and based on 16S rRNA sequence data, these isolates clustered together
      with the Leptospirillum ferrooxidans type strain (DSM2705 or L15). Group II
      leptospirilla had G+C moles percent ratios of 55 to 58% and had two copies of rrn
      genes, and based on 16S rRNA sequence data, they form a separate cluster. Genome
      DNA-DNA hybridization experiments indicated that three similarity subgroups were
      present among the leptospirilla tested, with two DNA-DNA hybridization similarity
      subgroups found within group I. The two groups could also be distinguished based
      on the sizes of their 16S-23S rRNA gene spacer regions. We propose that the group
      II leptospirilla should be recognized as a separate species with the name
      Leptospirillum ferriphilum sp. nov. Members of the two species can be rapidly
      distinguished from each other by amplification of their 16S rRNA genes and by
      carrying out restriction enzyme digests of the products. Several, but not all,
      isolates of the group II leptospirilla, but none from group I (L. ferrooxidans),
      were capable of growth at 45 degrees C. All the leptospirilla isolated from
      commercial biooxidation tanks in South Africa were from group II.

PMID- 11823227
TI  - Calnexin overexpression increases manganese peroxidase production in Aspergillus
      niger.
AB  - Heme-containing peroxidases from white rot basidiomycetes, in contrast to most
      proteins of fungal origin, are poorly produced in industrial filamentous fungal
      strains. Factors limiting peroxidase production are believed to operate at the
      posttranslational level. In particular, insufficient availability of the
      prosthetic group which is required for peroxidase biosynthesis has been proposed
      to be an important bottleneck. In this work, we analyzed the role of two
      components of the secretion pathway, the chaperones calnexin and binding protein
      (BiP), in the production of a fungal peroxidase. Expression of the Phanerochaete
      chrysosporium manganese peroxidase (MnP) in Aspergillus niger resulted in an
      increase in the expression level of the clxA and bipA genes. In a heme
      supplemented medium, where MnP was shown to be overproduced to higher levels,
      induction of clxA and bipA was also higher. Overexpression of these two
      chaperones in an MnP-producing strain was analyzed for its effect on MnP
      production. Whereas bipA overexpression seriously reduced MnP production,
      overexpression of calnexin resulted in a four- to fivefold increase in the
      extracellular MnP levels. However, when additional heme was provided in the
      culture medium, calnexin overexpression had no synergistic effect on MnP
      production. The possible function of these two chaperones in MnP maturation and
      production is discussed.

PMID- 11823228
TI  - Identical ring cleavage products during anaerobic degradation of naphthalene, 2
      methylnaphthalene, and tetralin indicate a new metabolic pathway.
AB  - Anaerobic degradation of naphthalene, 2-methylnaphthalene, and tetralin (1,2,3,4
      tetrahydronaphthalene) was investigated with a sulfate-reducing enrichment
      culture obtained from a contaminated aquifer. Degradation studies with tetralin
      revealed 5,6,7,8-tetrahydro-2-naphthoic acid as a major metabolite indicating
      activation by addition of a C(1) unit to tetralin, comparable to the formation of
      2-naphthoic acid in anaerobic naphthalene degradation. The activation reaction
      was specific for the aromatic ring of tetralin; 1,2,3,4-tetrahydro-2-naphthoic
      acid was not detected. The reduced 2-naphthoic acid derivatives tetrahydro-,
      octahydro-, and decahydro-2-naphthoic acid were identified consistently in
      supernatants of cultures grown with either naphthalene, 2-methylnaphthalene, or
      tetralin. In addition, two common ring cleavage products were identified. Gas
      chromatography-mass spectrometry (GC-MS) and high-resolution GC-MS analyses
      revealed a compound with a cyclohexane ring and two carboxylic acid side chains
      as one of the first ring cleavage products. The elemental composition was
      C(11)H(16)O(4) (C(11)H(16)O(4)-diacid), indicating that all carbon atoms of the
      precursor 2-naphthoic acid structure were preserved in this ring cleavage
      product. According to the mass spectrum, the side chains could be either an
      acetic acid and a propenic acid, or a carboxy group and a butenic acid side
      chain. A further ring cleavage product was identified as 2
      carboxycyclohexylacetic acid and was assumed to be formed by beta-oxidation of
      one of the side chains of the C(11)H(16)O(4)-diacid. Stable isotope-labeling
      growth experiments with either (13)C-labeled naphthalene, per-deuterated
      naphthalene-d(8), or a (13)C-bicarbonate-buffered medium showed that the ring
      cleavage products derived from the introduced carbon source naphthalene. The
      series of identified metabolites suggests that anaerobic degradation of
      naphthalenes proceeds via reduction of the aromatic ring system of 2-naphthoic
      acid to initiate ring cleavage in analogy to the benzoyl-coenzyme A pathway for
      monoaromatic hydrocarbons. Our findings provide strong indications that further
      degradation goes through saturated compounds with a cyclohexane ring structure
      and not through monoaromatic compounds. A metabolic pathway for anaerobic
      degradation of bicyclic aromatic hydrocarbons with 2-naphthoic acid as the
      central intermediate is proposed.

PMID- 11823229
TI  - Biotransformation and bioconcentration of steroid estrogens by Chlorella
      vulgaris.
AB  - The biotransformation and bioconcentration of natural and synthetic steroid
      estrogens by Chlorella vulgaris were investigated by using batch-shaking
      experiments with incubation for 48 h in the light or dark. Estradiol and estrone
      were interconvertible in both light and dark conditions; however, this
      biotransformation showed a preference for estrone. In the light, 50% estradiol
      was further metabolized to an unknown product. Apart from biotransformation,
      estrone, as well as hydroxyestrone, estriol, and ethinylestradiol, was relatively
      stable in the algal culture, whereas estradiol valerate was hydrolyzed to
      estradiol and then to estrone within 3 h of incubation. All of the tested
      estrogens exhibited a degree of partitioning to C. vulgaris; however, the
      concentrations of estriol, hydroxyestrone, ethinylestradiol, and estradiol
      valerate were always below the quantification limits. For estradiol and estrone,
      the partitioning of these estrogens in the algal extracts to the filtrates was
      <6% of the total amount present. The average concentration factor for estrone was
      ca. 27; however, the concentration factor for estradiol was not reported since no
      equilibrium was reached between the aqueous solution and that within the cells
      due to continuing biotransformation.

PMID- 11823230
TI  - Highly different levels of natural transformation are associated with genomic
      subgroups within a local population of Pseudomonas stutzeri from soil.
AB  - A highly sensitive and specific PCR-based method of monitoring 16S rRNA genes of
      Pseudomonas stutzeri was developed for searching P. stutzeri DNA in environmental
      samples. This monitoring was combined with a reliable and sensitive method for
      isolating P. stutzeri colony formers from soil and sediment, depending on their
      utilization of ethylene glycol, starch, and maltose. With these techniques, P.
      stutzeri populations (n = 2 to 170) were obtained from five of six sites giving
      positive PCR signals (including three marine sediment and two soil samples). The
      phylogenetic positions of isolates from the five sites, based on their 16S
      ribosomal DNA sequences, indicated that the environmental isolates were
      affiliated with different genomovars of P. stutzeri. Using the broad-host-range
      plasmid pNS1 with kanamycin and gentamicin resistance determinants as the
      transforming DNA, naturally transformable strains were identified among the
      isolates from all sites. For one population from soil, the genetic relationship
      of the 120 members was determined by randomly amplified polymorphic DNA-PCR with
      three PCR primers. Among the population members which are taxonomically closely
      related as determined by 16S sequence comparisons of group representatives, a
      rather high genetic diversity and a characteristic clustering into subgroups were
      found. Remarkably, within the population, nontransformability and different
      levels of transformability (a frequency between about 10(-9) and 10(-4) per cell)
      were often associated with distinct genetic subgroups. It is concluded that
      transformability is widespread among environmental P. stutzeri strains and that
      its specific level is a heritable trait that may vary strongly within a local
      population.

PMID- 11823231
TI  - Enzymatic manganese(II) oxidation by metabolically dormant spores of diverse
      Bacillus species.
AB  - Bacterial spores are renowned for their longevity, ubiquity, and resistance to
      environmental insults, but virtually nothing is known regarding whether these
      metabolically dormant structures impact their surrounding chemical environments.
      In the present study, a number of spore-forming bacteria that produce dormant
      spores which enzymatically oxidize soluble Mn(II) to insoluble Mn(IV) oxides were
      isolated from coastal marine sediments. The highly charged and reactive surfaces
      of biogenic metal oxides dramatically influence the oxidation and sorption of
      both trace metals and organics in the environment. Prior to this study, the only
      known Mn(II)-oxidizing sporeformer was the marine Bacillus sp. strain SG-1, an
      extensively studied bacterium in which Mn(II) oxidation is believed to be
      catalyzed by a multicopper oxidase, MnxG. Phylogenetic analysis based on 16S rRNA
      and mnxG sequences obtained from 15 different Mn(II)-oxidizing sporeformers
      (including SG-1) revealed extensive diversity within the genus Bacillus, with
      organisms falling into several distinct clusters and lineages. In addition,
      active Mn(II)-oxidizing proteins of various sizes, as observed in sodium dodecyl
      sulfate-polyacrylamide electrophoresis gels, were recovered from the outer layers
      of purified dormant spores of the isolates. These are the first active Mn(II)
      oxidizing enzymes identified in spores or gram-positive bacteria. Although
      extremely resistant to denaturation, the activities of these enzymes were
      inhibited by azide and o-phenanthroline, consistent with the involvement of
      multicopper oxidases. Overall, these studies suggest that the commonly held view
      that bacterial spores are merely inactive structures in the environment should be
      revised.

PMID- 11823232
TI  - Transcriptional and proteomic analysis of a ferric uptake regulator (fur) mutant
      of Shewanella oneidensis: possible involvement of fur in energy metabolism,
      transcriptional regulation, and oxidative stress.
AB  - The iron-directed, coordinate regulation of genes depends on the fur (ferric
      uptake regulator) gene product, which acts as an iron-responsive, transcriptional
      repressor protein. To investigate the biological function of a fur homolog in the
      dissimilatory metal-reducing bacterium Shewanella oneidensis MR-1, a fur knockout
      strain (FUR1) was generated by suicide plasmid integration into this gene and
      characterized using phenotype assays, DNA microarrays containing 691 arrayed
      genes, and two-dimensional polyacrylamide gel electrophoresis. Physiological
      studies indicated that FUR1 was similar to the wild-type strain when they were
      compared for anaerobic growth and reduction of various electron acceptors.
      Transcription profiling, however, revealed that genes with predicted functions in
      electron transport, energy metabolism, transcriptional regulation, and oxidative
      stress protection were either repressed (ccoNQ, etrA, cytochrome b and c
      maturation-encoding genes, qor, yiaY, sodB, rpoH, phoB, and chvI) or induced
      (yggW, pdhC, prpC, aceE, fdhD, and ppc) in the fur mutant. Disruption of fur also
      resulted in derepression of genes (hxuC, alcC, fhuA, hemR, irgA, and ompW)
      putatively involved in iron uptake. This agreed with the finding that the fur
      mutant produced threefold-higher levels of siderophore than the wild-type strain
      under conditions of sufficient iron. Analysis of a subset of the FUR1 proteome
      (i.e., primarily soluble cytoplasmic and periplasmic proteins) indicated that 11
      major protein species reproducibly showed significant (P < 0.05) differences in
      abundance relative to the wild type. Protein identification using mass
      spectrometry indicated that the expression of two of these proteins (SodB and
      AlcC) correlated with the microarray data. These results suggest a possible
      regulatory role of S. oneidensis MR-1 Fur in energy metabolism that extends the
      traditional model of Fur as a negative regulator of iron acquisition systems.

PMID- 11823234
TI  - Assessment of fluorochromes for two-photon laser scanning microscopy of biofilms.
AB  - A major limitation for the use of two-proton laser scanning microscopy (2P-LSM)
      in biofilm and other studies is the lack of a thorough understanding of the
      excitation-emission responses of potential fluorochromes. In order to use 2P-LSM,
      the utility of various fluorochromes and probes specific for a range of biofilm
      constituents must be evaluated. The fluorochromes tested in this study included
      classical nucleic acid-specific stains, such as acridine orange (AO) and 4",6"
      diamidino-2-phenylindole (DAPI), as well as recently developed stains. In
      addition, stains specific for biofilm extracellular polymeric substances (EPS
      matrix components) were tested. Two-photon excitation with a Ti/Sapphire laser
      was carried out at wavelengths from 760 to 900 nm in 10-nm steps. It was found
      that autofluorescence of phototrophic organisms (cyanobacteria and green algae)
      resulted in strong signals for the entire excitation range. In addition, the
      coenzyme F(420)-related autofluorescence of methanogenic bacteria could be used
      to obtain images of dense aggregates (excitation wavelength, 780 nm). The
      intensities of the emission signals for the nucleic acid-specific fluorochromes
      varied. For example, the intensities were similar for excitation wavelengths
      ranging from 780 to 900 nm for AO but were higher for a narrower range, 780 to
      810 nm, for DAPI. In selective excitation, fading, multiple staining, and
      combined single-photon-two-photon studies, the recently developed nucleic acid
      specific fluorochromes proved to be more suitable regardless of whether they are
      intended for living or fixed samples. Probes specific for proteins and
      glycoconjugates allowed two-photon imaging of polymeric biofilm constituents.
      Selective excitation-emission was observed for Calcofluor White M2R (780 to 800
      nm) and SyproOrange (880 to 900 nm). In addition, fluor-conjugated concanavalin A
      lectins were examined and provided acceptable two-photon emission signals at
      wavelengths ranging from 780 to 800 nm. Finally, CellTracker, a fluorochrome
      suitable for long-term labeling of microbial eucaryote cells, was found to give
      strong emission at wavelengths ranging from 770 to 810 nm. If fluorochromes have
      the same two-photon excitation cross section, they are suitable for multiple
      staining and multichannel recording. Generally, if an appropriate excitation
      wavelength and fluorochrome were used, it was possible to obtain more highly
      resolved images for thick biofilm samples with two-photon laser microscopy than
      with conventional single-photon laser microscopy. Due to its potential for higher
      resolution in light-scattering tissue-like material, such as biofilms, and
      extremely localized excitation, 2P-LSM is a valuable addition to conventional
      confocal laser scanning microscopy with single-photon excitation. However,
      further development of the method and basic research are necessary to take full
      advantage of nonlinear excitation in studies of interfacial microbial ecology.

PMID- 11823233
TI  - Characterization and description of Anaeromyxobacter dehalogenans gen. nov., sp.
      nov., an aryl-halorespiring facultative anaerobic myxobacterium.
AB  - Five strains were isolated which form a physiologically and phylogenetically
      coherent group of chlororespiring microorganisms and represent the first taxon in
      the Myxobacteria capable of anaerobic growth. The strains were enriched and
      isolated from various soils and sediments based on their ability to grow using
      acetate as an electron donor and 2-chlorophenol (2-CPh) as an electron acceptor.
      They are slender gram-negative rods with a bright red pigmentation that exhibit
      gliding motility and form spore-like structures. These unique chlororespiring
      myxobacteria also grow with 2,6-dichlorophenol, 2,5-dichlorophenol, 2
      bromophenol, nitrate, fumarate, and oxygen as terminal electron acceptors, with
      optimal growth occurring at low concentrations (<1 mM) of electron acceptor. 2
      CPh is reduced by all strains as an electron acceptor in preference to nitrate,
      which is reduced to ammonium. Acetate, H(2), succinate, pyruvate, formate, and
      lactate were used as electron donors. None of the strains grew by fermentation.
      The 16S ribosomal DNA (rDNA) sequences of the five strains form a coherent
      cluster deeply branching within the family Myxococcaceae within the class
      Myxobacteria and are mostly closely associated with the Myxococcus subgroup. With
      the exception of anaerobic growth and lack of a characteristic fruiting body,
      these strains closely resemble previously characterized myxobacteria and
      therefore should be considered part of the Myxococcus subgroup. The anaerobic
      growth and 9.0% difference in 16S rDNA sequence from those of other myxobacterial
      genera are sufficient to place these strains in a new genus and species
      designated Anaeromyxobacter dehalogenans. The type strain is 2CP-1 (ATCC BAA
      258).

PMID- 11823236
TI  - Production of human papillomavirus type 16 E7 protein in Lactococcus lactis.
AB  - The E7 protein of human papillomavirus type 16 was produced in Lactococcus
      lactis. Secretion allowed higher production yields than cytoplasmic production.
      In stationary phase, amounts of cytoplasmic E7 were reduced, while amounts of
      secreted E7 increased, suggesting a phase-dependent intracellular proteolysis.
      Fusion of E7 to the staphylococcal nuclease, a stable protein, resulted in a
      highly stable cytoplasmic protein. This work provides new candidates for
      development of viral screening systems and for oral vaccine against cervical
      cancer.

PMID- 11823237
TI  - Heavy metal resistance patterns of Frankia strains.
AB  - The sensitivity of 12 Frankia strains to heavy metals was determined by a growth
      inhibition assay. In general, all of the strains were sensitive to low
      concentrations (<0.5 mM) of Ag(1+), AsO(2)(1-), Cd(2+), SbO(2)(1-), and Ni(2+),
      but most of the strains were less sensitive to Pb(2+) (6 to 8 mM), CrO(4)(2-)
      (1.0 to 1.75 mM), AsO(4)(3-) (>50 mM), and SeO(2)(2-) (1.5 to 3.5 mM). While most
      strains were sensitive to 0.1 mM Cu(2+), four strains were resistant to elevated
      levels of Cu(2+) (2 to 5 mM and concentrations as high as 20 mM). The mechanism
      of SeO(2)(2-) resistance seems to involve reduction of the selenite oxyanion to
      insoluble elemental selenium, whereas Pb(2+) resistance and Cu(2+) resistance may
      involve sequestration or binding mechanisms. Indications of the resistance
      mechanisms for the other heavy metals were not as clear.

PMID- 11823235
TI  - Production and targeting of the Brucella abortus antigen L7/L12 in Lactococcus
      lactis: a first step towards food-grade live vaccines against brucellosis.
AB  - Brucella abortus is a facultative intracellular gram-negative bacterial pathogen
      that infects humans and animals by entry mainly through the digestive tract. B.
      abortus causes abortion in pregnant cattle and undulant fever in humans. The
      immunogenic B. abortus ribosomal protein L7/L12 is a promising candidate antigen
      for the development of oral live vaccines against brucellosis, using food-grade
      lactic acid bacteria (LAB) as a carrier. The L7/L12 gene was expressed in
      Lactococcus lactis, the model LAB, under the nisin-inducible promoter. Using
      different signals, L7/L12 was produced in cytoplasmic, cell-wall-anchored, and
      secreted forms. Cytoplasmic production of L7/L12 gave a low yield, estimated at
      0.5 mg/liter. Interestingly, a secretable form of this normally cytoplasmic
      protein via fusion with a signal peptide resulted in increased yield of L7/L12 to
      3 mg/liter; secretion efficiency (SE) was 35%. A fusion between the mature moiety
      of the staphylococcal nuclease (Nuc) and L7/L12 further increased yield to 8
      mg/liter. Fusion with a synthetic propeptide (LEISSTCDA) previously described as
      an enhancer for heterologous protein secretion in L. lactis (Y. Le Loir, A.
      Gruss, S. D. Ehrlich, and P. Langella, J. Bacteriol. 180:1895-1903, 1998) raised
      the yield to 8 mg/liter and SE to 50%. A surface-anchored L7/L12 form in L.
      lactis was obtained by fusing the cell wall anchor of Streptococcus pyogenes M6
      protein to the C-terminal end of L7/L12. The fusions described allow the
      production and targeting of L7/L12 in three different locations in L. lactis.
      This is the first example of a B. abortus antigen produced in a food-grade
      bacterium and opens new perspectives for alternative vaccine strategies against
      brucellosis.

PMID- 11823238
TI  - Alkaline phosphatase reporter transposon for identification of genes encoding
      secreted proteins in gram-positive microorganisms.
AB  - We describe the construction of TnFuZ, a genetic tool for the discovery and
      mutagenesis of proteins exported from gram-positive bacteria. This tool combines
      a transposable element (Tn4001) of broad host range in gram-positive bacteria and
      an alkaline phosphatase gene (phoZ) derived from a gram-positive bacterium that
      has been modified by removal of the region encoding its export signal.
      Mutagenesis of Streptococcus pyogenes with TnFuZ ("FuZ" stands for fusions to
      phoZ) identified genes encoding secreted proteins whose expression was enhanced
      during growth in an aerobic environment. Thus, TnFuZ should be valuable for
      analysis of protein secretion, gene regulation, and virulence in gram-positive
      bacteria.

PMID- 11823239
TI  - Natural communities of novel archaea and bacteria with a string-of-pearls-like
      morphology: molecular analysis of the bacterial partners.
AB  - A recently discovered bacterial/archaeal association, growing in a string-of
      pearls-like structure, thrives in the cold (approximately 10 degrees C) sulfidic
      marsh water of the Sippenauer Moor near Regensburg, Bavaria, Germany. It forms
      characteristic, macroscopically visible globules, the pearls, containing
      microcolonies of novel euryarchaeota, which are surrounded by mainly filamentous
      bacteria (C. Rudolph, G. Wanner, and R. Huber, Appl. Environ. Microbiol. 67:2336
      2344, 2001). Single pearls in series are connected by white threads. Here we
      report the first detailed molecular investigations of the taxonomic affiliation
      of the bacteria contributing to the strings of pearls. Phylogenetic analysis
      showed the dominance of a single phylotype (clone sipK4) within single pearls
      most closely related to Thiothrix unzii. The presence of Thiothrix sipK4 as a
      major constituent of single pearls and of the pearl-connecting white threads was
      verified by fluorescence in situ hybridization.

PMID- 11823240
TI  - Streptococcus thermophilus is able to produce a beta-galactosidase active during
      its transit in the digestive tract of germ-free mice.
AB  - This work presents data on the application of a bacterial luciferase used to
      monitor gene expression of Streptococcus thermophilus in the digestive tract. The
      main result is that the bacterium was able to produce an active beta
      galactosidase in the digestive tract, although it did not multiply during its
      transit. This production was enhanced when lactose (the inducer) was added to the
      diet.

PMID- 11823241
TI  - Genetic and immunochemical characterization of thiocyanate-degrading bacteria in
      lake water.
AB  - Natural aquatic and soil samples were screened for the presence of thiocyanate
      degrading bacteria. Using thiocyanate supplementation, we established an
      enrichment culture containing such bacteria from lake water. The dominant
      bacteria had the scnC-LS5 gene encoding thiocyanate hydrolase, which was closely
      related to the enzyme found previously in Thiobacillus thioparus THI115 isolated
      from activated sludge.

PMID- 11823243
TI  - Rapid two-step procedure for large-scale purification of pediocin-like
      bacteriocins and other cationic antimicrobial peptides from complex culture
      medium.
AB  - A rapid and simple two-step procedure suitable for both small- and large-scale
      purification of pediocin-like bacteriocins and other cationic peptides has been
      developed. In the first step, the bacterial culture was applied directly on a
      cation-exchange column (1-ml cation exchanger per 100-ml cell culture). Bacteria
      and anionic compounds passed through the column, and cationic bacteriocins were
      subsequently eluted with 1 M NaCl. In the second step, the bacteriocin fraction
      was applied on a low-pressure, reverse-phase column and the bacteriocins were
      detected as major optical density peaks upon elution with propanol. More than 80%
      of the activity that was initially in the culture supernatant was recovered in
      both purification steps, and the final bacteriocin preparation was more than 90%
      pure as judged by analytical reverse-phase chromatography and capillary
      electrophoresis.

PMID- 11823242
TI  - Two forms of NAD-dependent D-mandelate dehydrogenase in Enterococcus faecalis IAM
      10071.
AB  - Two forms of NAD-dependent D-mandelate dehydrogenase (D-ManDHs) were purified
      from Enterococcus faecalis IAM 10071. While these two enzymes consistently
      exhibited high activity toward large 2-ketoacid substrates that were branched at
      the C3 or C4 position, they gave distinctly different K(m) and V(max) values for
      these substrates and had distinct molecular weights by gel electrophoresis and
      gel filtration.

PMID- 11823245
TI  - Microbial growth inside insulated external walls as an indoor air
      biocontamination source.
AB  - The association between moisture-related microbial growth (mesophilic fungi and
      bacteria) within insulated exterior walls and microbial concentrations in the
      indoor air was studied. The studied apartment buildings with precast concrete
      external walls were situated in a subarctic zone. Actinomycetes in the insulation
      layer were found to have increased concentrations in the indoor air. The moisture
      content of the indoor air significantly affected all measurable airborne
      concentrations.

PMID- 11823244
TI  - Coexistence of two distinct copies of naphthalene degradation genes in
      Pseudomonas strains isolated from the western Mediterranean region.
AB  - We analyzed the occurrence of the naphthalene degradation upper-pathway (nah)
      genes in the western Mediterranean region. The amplification, restriction, and
      sequence analysis of internal fragments for several nah genes (nahAc, nahB, nahC,
      and nahE) from naphthalene-degrading strains isolated from this geographical area
      proved the coexistence of two distinct sets of nah genes.

PMID- 11823246
TI  - Chemotaxis of Ralstonia eutropha JMP134(pJP4) to the herbicide 2,4
      dichlorophenoxyacetate.
AB  - Ralstonia eutropha JMP134(pJP4) and several other species of motile bacteria can
      degrade the herbicide 2,4-dichlorophenoxyacetate (2,4-D), but it was not known if
      bacteria could sense and swim towards 2,4-D by the process of chemotaxis. Wild
      type R. eutropha cells were chemotactically attracted to 2,4-D in swarm plate
      assays and qualitative capillary assays. The chemotactic response was induced by
      growth with 2,4-D and depended on the presence of the catabolic plasmid pJP4,
      which harbors the tfd genes for 2,4-D degradation. The tfd cluster also encodes a
      permease for 2,4-D named TfdK. A tfdK mutant was not chemotactic to 2,4-D, even
      though it grew at wild-type rates on 2,4-D.

PMID- 11823247
TI  - Isolation and characterization of bacteriophages from fermenting sauerkraut.
AB  - This paper presents the first report of bacteriophage isolated from commercial
      vegetable fermentations. Nine phages were isolated from two 90-ton commercial
      sauerkraut fermentations. These phages were active against fermentation isolates
      and selected Leuconostoc mesenteroides and Lactobacillus plantarum strains,
      including a starter culture. Phages were characterized as members of the
      Siphoviridae and Myoviridae families. All Leuconostoc phages reported previously,
      primarily of dairy origin, belonged to the Siphoviridae family.

PMID- 11823248
TI  - Rapid identification of probiotic lactobacillus biosurfactant proteins by
      ProteinChip tandem mass spectrometry tryptic peptide sequencing.
AB  - A novel ProteinChip-interfaced tandem mass spectrometer was employed to identify
      collagen binding proteins from biosurfactant produced by Lactobacillus fermentum
      RC-14. On-chip tryptic digestion of the captured collagen binding proteins
      resulted in rapid sequence identification of five novel tryptic peptide sequences
      via collision-induced dissociation tandem mass spectrometry.

PMID- 11823249
TI  - Effect of oxidizing disinfectants (chlorine, monochloramine, and ozone) on
      Helicobacter pylori.
AB  - The susceptibility of Helicobacter pylori to disinfectants was compared to that
      of Escherichia coli. H. pylori is more resistant than E. coli to chlorine and
      ozone but not monochloramine. H. pylori may be able to tolerate disinfectants in
      distribution systems and, therefore, may be transmitted by a waterborne route.

PMID- 11823250
TI  - Involvement of glnB, glnZ, and glnD genes in the regulation of poly-3
      hydroxybutyrate biosynthesis by ammonia in Azospirillum brasilense Sp7.
AB  - The role of three key nitrogen regulatory genes, glnB (encoding the P(II)
      protein), glnZ (encoding the P(z) protein), and glnD (encoding the GlnD protein),
      in regulation of poly-3-hydroxybutyrate (PHB) biosynthesis by ammonia in
      Azospirillum brasilense Sp7 was investigated. It was observed that glnB glnZ and
      glnD mutants produce substantially higher amounts of PHB than the wild type
      produces during the active growth phase. glnB and glnZ mutants have PHB
      production phenotypes similar to that of the wild type. Our results indicate that
      the P(II)-P(z) system is apparently involved in nitrogen-dependent regulation of
      PHB biosynthesis in A. brasilense Sp7.

PMID- 11823251
TI  - Detection and quantification of Pfiesteria piscicida by using the mitochondrial
      cytochrome b gene.
AB  - Mitochondrial cytochrome b was isolated from the dinoflagellate Pfiesteria
      piscicida, and the utility of the gene for species identification was examined.
      One of the primer sets designed was shown to be highly specific for P. piscicida.
      A time step PCR protocol was used to demonstrate the potential of this primer set
      for quantification of this species.

PMID- 11823252
TI  - Simple procedure for rapid identification of Vibrio cholerae from the aquatic
      environment.
AB  - Biochemical tests commonly used to screen for Vibrio cholerae in environmental
      samples were evaluated, and we found that a combination of alkaline peptone
      enrichment followed by streaking on thiosulfate citrate bile salts sucrose agar
      and testing for arginine dihydrolase activity and esculin hydrolysis was an
      effective rapid technique to screen for aquatic environmental V. cholerae. This
      technique provided 100% sensitivity and > or =70% specificity.

PMID- 11823253
TI  - Novel clade of Rickettsia spp. from leeches.
AB  - Intracellular rickettsia-like structures were found in the tissues of a
      glossiphoniid leech, Torix tagoi, by transmission electron microscopy. Diagnostic
      PCR analysis using specific primers suggested that of the nine glossiphoniid
      species examined, two species, T. tagoi and Hemicrepsis marginata, harbored
      bacteria of the genus Rickettsia. A 1.5-kb eubacterial 16S rRNA gene segment
      obtained from each of these species was amplified by PCR, cloned, and sequenced.
      Phylogenetic analysis of the 16S rRNA gene demonstrated that the Rickettsia
      species found in the leeches constituted a novel clade that is distinct from the
      clade of arthropod-associated Rickettsia species. In natural populations, 97.7%
      (43 of 44) of T. tagoi leeches and 100% (9 of 9) of H. marginata leeches carried
      Rickettsia, suggesting that infection with Rickettsia is prevalent in these
      leeches. This is the first report of Rickettsia found in annelids.

PMID- 11823254
TI  - Tolerance and metabolic response of acetogenic bacteria toward oxygen.
AB  - The acetogens Sporomusa silvacetica, Moorella thermoacetica, Clostridium magnum,
      Acetobacterium woodii, and Thermoanaerobacter kivui (i) grew in both semisolid
      and liquid cultivation media containing O(2) and (ii) consumed small amounts of
      O(2). Low concentrations of O(2) caused a lag phase in growth but did not alter
      the ability of these acetogens to synthesize acetate via the acetyl coenzyme A
      pathway. Cell extracts of S. silvacetica, M. thermoacetica, and C. magnum
      contained peroxidase and NADH oxidase activities; catalase and superoxide
      dismutase activities were not detected.

PMID- 11823255
TI  - Quantitation of DNA sequences in environmental PCR products by a multiplexed,
      bead-based method.
AB  - A first application of a multiplexed, bead-based method is described for
      determining the abundances of target sequences in an environmental PCR product.
      Target sequences as little as 0.3% of the total amount of DNA can be quantified.
      Tests were conducted on 16S ribosomal DNA sequences from microorganisms collected
      from contaminated groundwater.

PMID- 11823256
TI  - Atypical antipsychotic medications and the treatment of schizophrenia.

PMID- 11823257
TI  - Amisulpride, an unusual "atypical" antipsychotic: a meta-analysis of randomized
      controlled trials.
AB  - OBJECTIVE: The "atypical" profile of the new antipsychotics clozapine,
      olanzapine, quetiapine, and risperidone has been linked to combined antagonism of
      serotonin 2 (5-HT(2)) and dopamine 2 (D(2)) receptors. Although amisulpride is a
      highly selective D(3)/D(2) receptor antagonist, it is assumed to have atypical
      properties as well. The purpose of this article was to compare the atypical
      profile of amisulpride with that of the 5-HT(2)/D(2) antagonists. METHOD:
      Randomized controlled trials that compared amisulpride with conventional
      antipsychotics or placebo for patients with schizophrenia were identified and
      included in a meta-analysis. The mean effect sizes found for amisulpride were
      compared with those of an updated meta-analysis of the 5-HT(2)/D(2) antagonists.
      RESULTS: Eighteen randomized controlled trials of amisulpride (N=2,214) were
      found. In 11 studies of acutely ill patients it proved to be consistently more
      effective than conventional antipsychotics for global schizophrenic symptoms
      (measured with the Brief Psychiatric Rating Scale) and negative symptoms.
      Amisulpride is to date the only atypical antipsychotic for which several studies
      of patients suffering predominantly from negative symptoms have been published.
      In four such studies amisulpride was significantly more effective than placebo.
      Three small studies with conventional antipsychotics as comparators showed only a
      trend in favor of amisulpride in this regard. Amisulpride was associated with
      clearly lower use of antiparkinsonian medication and with fewer dropouts due to
      adverse events than conventional antipsychotics. CONCLUSIONS: These results cast
      some doubt on the notion that combined 5-HT(2)/D(2) antagonism is the reason that
      the newer antipsychotic medications are effective for negative symptoms and have
      fewer extrapyramidal side effects.

PMID- 11823258
TI  - A reevaluation of the exclusion criteria used in antidepressant efficacy trials.
AB  - OBJECTIVE: Antidepressant efficacy trials use multiple exclusion criteria that
      are intended primarily to maximize differences between the drug and placebo.
      These exclusion criteria were implemented prior to having undergone rigorous
      testing, however, and it is unclear whether they accomplish their intended goal.
      The authors review the current state of knowledge about treatment response rates
      in individuals who are typically excluded from antidepressant efficacy trials.
      METHOD: After reviewing 31 antidepressant efficacy trials published between 1994
      and 1998, the authors identified 10 commonly used exclusion criteria. A
      computerized MEDLINE search and a manual search were used to identify studies
      evaluating the efficacy of antidepressant medications in populations of subjects
      typically excluded from antidepressant efficacy trials. RESULTS: Three exclusion
      criteria-short episode duration, mild severity of illness, and positive response
      during the placebo lead-in phase-are used primarily to reduce placebo response
      rates. Preliminary evidence suggests that, of those three criteria, only a short
      episode duration has been associated with less robust differences between drug
      and placebo response rates. The seven other exclusion criteria, including various
      psychiatric comorbidities, long duration of illness, medical comorbidity, and
      prior nonresponse to treatment, are used because individuals who meet those
      criteria are believed to have lower response rates to somatic therapy. Although
      such individuals are often found to have lower response rates to somatic therapy,
      they also appear to have lower response rates to placebo, and there is little
      evidence to suggest that drug-placebo differences are any less robust in these
      individuals. CONCLUSIONS: Many of the standard exclusion criteria currently used
      in antidepressant efficacy trials may not be achieving their intended goal of
      maximizing drug-placebo differences. The practice of excluding subjects with
      particular clinical profiles, which greatly reduces the generalizability of
      antidepressant efficacy trials, appears to lack empirical support.

PMID- 11823260
TI  - The human genome: proteomics.

PMID- 11823259
TI  - Community-based intervention research: coping with the "noise" of real life in
      study design.
AB  - The ultimate goal of clinical intervention research is to find a way to improve
      the care and lives of people suffering from specific psychiatric symptoms,
      illnesses, and/or disabilities. This article provides to clinical researchers a
      set of issues to consider and steps to follow in making the transition to more
      public-health-oriented, community-based research. Traditional, academically
      based, randomized clinical trials test an intervention against a placebo or
      alternate treatment control condition, focusing on a single, specific main
      outcome. Community-based intervention trials also test a treatment intervention
      but in the context of the community environment. These trials, in order to
      provide meaningful information for community clinical practice, must take into
      account many factors that are controlled or are not considered in traditional
      clinical trials. Investigators need to be clear about the goal of community-based
      interventions; they need to determine the social and cultural norms,
      expectations, and conflicts of the community and of the setting, and they need to
      work collaboratively with experts in both qualitative and quantitative design.

PMID- 11823261
TI  - Treatment of a dually diagnosed gay male patient: a psychotherapy perspective.

PMID- 11823262
TI  - Max Schur, M.D., 1897-1969.

PMID- 11823263
TI  - Neuropsychological correlates of hippocampal volumes in patients experiencing a
      first episode of schizophrenia.
AB  - OBJECTIVE: Despite evidence for hippocampal structural abnormalities in patients
      with schizophrenia, their functional correlates remain largely unknown. This
      study investigated the neuropsychological correlates of hippocampal volume in 43
      men and 32 women experiencing a first episode of schizophrenia. METHOD: Posterior
      and anterior hippocampal volumes were computed from contiguous 3.1-mm magnetic
      resonance images and examined in relationship to six domains of
      neuropsychological functioning. Significant structure-function associations were
      investigated by examining the correlations between functioning and individual
      hippocampal slice volumes across the long axis of the hippocampus after
      interpolation to 10 equally spaced slice positions. RESULTS: Among men, worse
      executive and motor functioning correlated significantly with smaller anterior,
      but not posterior, hippocampal volume. The relationship between executive and
      motor functioning and hippocampal volume was not linear, however, when examined
      across the long axis of the hippocampus. Anterior hippocampal volume was more
      strongly correlated with both executive and motor functioning than with either
      memory or language functioning in men. None of the correlations between either
      posterior or anterior hippocampal volumes and the neuropsychological domains was
      significant among women. Anterior hippocampal volume was more strongly correlated
      with motor functioning in men than in women. CONCLUSIONS: Anterior hippocampal
      abnormalities associated with deficits on tests considered sensitive to frontal
      lobe functions implicate a defect in the integrated system linking frontal and
      mesiotemporal lobe regions. These findings further suggest that there are sex
      differences in structure-function relations in schizophrenia such that men may
      have more pronounced frontolimbic system abnormalities.

PMID- 11823264
TI  - A PET study of the pathophysiology of negative symptoms in schizophrenia.
      Positron emission tomography.
AB  - OBJECTIVE: Positron emission tomography (PET) was used to compare cerebral
      metabolic patterns in schizophrenic subjects with predominantly negative symptoms
      (alogia, affective flattening, avolition, and attentional impairment) and in
      those with predominantly positive symptoms. METHOD: Fourteen right-handed male
      subjects with DSM-IV schizophrenia were assigned to groups with predominantly
      negative or predominantly positive symptoms on the basis of their post-drug
      washout scores on the Positive and Negative Syndrome Scale. The patients were
      compared to seven age- and gender-matched normal volunteers. PET scans with
      [(18)F]fluorodeoxyglucose were obtained during a degraded Continuous Performance
      Task to measure absolute glucose metabolic rates. Statistical parametric mapping
      was used to estimate the regional metabolic differences between groups. RESULTS:
      The subjects with predominantly negative symptoms had significant differences in
      glucose metabolic rates, compared to both the subjects with predominantly
      positive symptoms and the normal subjects. Negative symptom subjects had a lower
      glucose metabolic rate in the right hemisphere, especially in the temporal and
      ventral prefrontal cortices, compared to the other groups, and higher metabolic
      rates in the cerebellar cortex and in the lower deep cerebellar nuclei. Negative
      symptom subscale scores were negatively correlated with glucose metabolic rates
      for most of the brain areas that differentiated subjects with predominantly
      negative symptoms from those with predominantly positive symptoms. CONCLUSIONS:
      Schizophrenic subjects with predominantly negative symptoms have greater
      metabolic abnormalities than subjects with predominantly positive symptoms,
      particularly in frontal, temporal, and cerebellar circuitry. These results are
      consistent with abnormalities in corticocortical, corticobasal ganglia,
      mesocortical dopamine, and cerebellar-thalamic-prefrontal circuits, which may
      underlie the negative symptoms of schizophrenia.

PMID- 11823265
TI  - Minor physical anomalies and schizophrenia spectrum disorders: a prospective
      investigation.
AB  - OBJECTIVE: The authors prospectively assessed the relationship between minor
      physical anomalies identified in childhood and adult psychiatric outcome. METHOD:
      In 1972, minor physical anomalies were measured in a group of 265 Danish children
      ages 11-13. The examination was part of a larger study investigating early signs
      of schizophrenia spectrum disorders. Many of the subjects had a parent with
      schizophrenia, leaving them at high risk for developing a schizophrenia spectrum
      disorder. In 1991, adult psychiatric outcome data were obtained for 91.3% (N=242)
      of the original subjects, including 81 who were at high risk. RESULTS:
      Individuals with a high number of minor physical anomalies developed
      schizophrenia spectrum disorders significantly more often than they developed a
      no mental illness outcome. Further, individuals with a high number of minor
      physical anomalies tended to develop schizophrenia spectrum disorders more often
      than other psychopathology. Among individuals at genetic high risk, higher
      numbers of minor physical anomalies may interact with pre-existing
      vulnerabilities for schizophrenia to increase the likelihood of a schizophrenia
      spectrum disorder outcome. CONCLUSIONS: Minor physical anomalies may provide
      important clues to understanding schizophrenia spectrum disorders from a
      neurodevelopmental perspective. Minor physical anomalies appear to signal
      stressors relevant to schizophrenia spectrum development, especially in those at
      genetic risk for schizophrenia.

PMID- 11823266
TI  - Volume changes in gray matter in patients with schizophrenia.
AB  - OBJECTIVE: Schizophrenia is generally characterized by a progressive decline in
      functioning. Although structural brain abnormalities, particularly decrements in
      gray matter volume, are considered important to the pathology of schizophrenia,
      it is not resolved whether the brain abnormalities become more prominent over
      time. METHOD: Magnetic resonance brain images from 159 patients with
      schizophrenia and 158 healthy comparison subjects between 16 and 70 years of age
      were compared. Using linear regression analysis, the authors analyzed the
      relationship between the volumes of the total brain, gray and white matter,
      cerebellum, and lateral and third ventricles with patient age. RESULTS: Total
      brain (-2.2%), cerebral gray matter (-3.3%), prefrontal gray matter (-4.4%), and
      prefrontal white matter (-3.5%) volumes were smaller, and lateral (27%) and third
      (30%) ventricle and peripheral CSF (11%) volumes were larger in schizophrenia
      patients. A significant group-by-age interaction for gray matter volume was
      found, as shown by a steeper regression slope between age and gray matter volume
      in patients (-3.43 ml/year) than in healthy comparison subjects (-2.74 ml/year).
      CONCLUSIONS: The smaller brains of the patients with schizophrenia can be
      explained by decreases in gray matter volume. Moreover, the finding that the
      smaller gray matter volume was more pronounced in older patients with
      schizophrenia may suggest progressive loss of cerebral gray matter in
      schizophrenia patients.

PMID- 11823267
TI  - Anterior cingulate activation during Stroop task performance: a PET to MRI
      coregistration study of individual patients with schizophrenia.
AB  - OBJECTIVE: The authors used single-subject functional imaging analyses to 1)
      corroborate the findings of anterior cingulate hypoperfusion during an
      attentional task in schizophrenia and 2) examine whether anterior cingulate
      activation is associated with underlying morphology. METHOD: Five healthy
      subjects and six patients with schizophrenia underwent positron emission
      tomography scanning while they performed the Stroop task. The medial-frontal
      lobes were masked out for analysis, and activation peaks were individually
      coregistered to each subject's magnetic resonance imaging scan. RESULTS: Healthy
      subjects showed activations in both limbic and paralimbic anterior cingulate
      regions. Patients with schizophrenia showed only paralimbic activations, and
      these were apparent only in patients having a paracingulate sulcus. CONCLUSIONS:
      These findings suggest that 1) patients with schizophrenia have limbic-anterior
      cingulate hypoperfusion during attentional tasks and 2) paralimbic activation is
      associated with underlying morphology.

PMID- 11823269
TI  - Symptom stability in adult obsessive-compulsive disorder: data from a
      naturalistic two-year follow-up study.
AB  - OBJECTIVE: Little is known about the longitudinal course of symptoms in adult
      patients with obsessive-compulsive disorder (OCD), although some evidence exists
      regarding symptom stability in children and adolescents. This study
      systematically investigated the temporal stability of individual symptoms and
      symptom dimensions of OCD in adult patients who were followed prospectively for 2
      years. METHOD: One hundred seventeen adult outpatients with OCD from three U.S.
      sites were administered the Yale-Brown Obsessive Compulsive Scale symptom
      checklist four times over a period of 2 years. Eighty-one (69%), 83 (71%), and 67
      (57%) patients were available 6 months, 1 year, and 2 years after initial
      screening, respectively. Different analytic methods assessed the stability of OCD
      symptoms within and between previously identified symptom dimensions. RESULTS:
      For the most part, patients maintained their symptoms throughout follow-up,
      although some symptoms were more stable than others. For the symptoms that
      changed, changes occurred within rather than between symptom dimensions;
      qualitative shifts from one dimension to another were rare. The strongest
      predictor of the presence of a particular symptom was having had that symptom in
      the past. Although most patients had received pharmacological and behavioral
      treatment during the follow-up period, changes within symptom dimensions could
      not be explained by overall clinical improvement over time. CONCLUSIONS: Symptoms
      of adult patients with OCD might be more stable across time than previously
      thought, with some symptoms waxing and waning within symptom dimensions and
      rarely involving shifts between dimensions. Longer follow-up studies involving
      larger samples are needed to better understand the fluctuations of OCD symptoms
      across time.

PMID- 11823268
TI  - Clozapine, olanzapine, risperidone, and haloperidol in the treatment of patients
      with chronic schizophrenia and schizoaffective disorder.
AB  - OBJECTIVE: The authors compared the efficacy and safety of three atypical
      antipsychotics (clozapine, olanzapine, and risperidone) with one another and with
      haloperidol in the treatment of patients with chronic schizophrenia or
      schizoaffective disorder. METHOD: In a double-blind trial, 157 inpatients with a
      history of suboptimal treatment response were randomly assigned to treatment with
      clozapine, olanzapine, risperidone, or haloperidol for 14 weeks (an 8-week
      escalation and fixed-dose period followed by a 6-week variable-dose period).
      RESULTS: Clozapine, risperidone, and olanzapine (but not haloperidol) resulted in
      statistically significant improvements in total score on the Positive and
      Negative Syndrome Scale. Improvements seen in total and negative symptom scores
      with clozapine and olanzapine were superior to haloperidol. The atypical drugs,
      particularly olanzapine and clozapine, were associated with weight gain.
      CONCLUSIONS: The effects of atypical antipsychotics in this population were
      statistically significant but clinically modest. The overall pattern of results
      suggests that clozapine and olanzapine have similar general antipsychotic
      efficacy and that risperidone may be somewhat less effective. Clozapine was the
      most effective treatment for negative symptoms. However, the differences among
      treatments were small.

PMID- 11823270
TI  - Prospective long-term follow-up of 44 patients who received cingulotomy for
      treatment-refractory obsessive-compulsive disorder.
AB  - OBJECTIVE: Long-term outcome associated with cingulotomy for obsessive-compulsive
      disorder (OCD) was prospectively assessed. Findings are reported for 18 patients
      previously described in 1995 and for 26 new patients. METHOD: An open
      preoperative and follow-up assessment was conducted at multiple time points for
      44 patients undergoing one or more cingulotomies for treatment-refractory OCD.
      The patients were assessed by using the Structured Clinical Interview for DSM-III
      R preoperatively and with the Yale-Brown Obsessive Compulsive Scale, the Beck
      Depression Inventory, and the Sickness Impact Profile both preoperatively and at
      all follow-up assessments. The patients completed clinical global improvement
      scales at all follow-up assessments. RESULTS: At mean follow-up of 32 months
      after one or more cingulotomies, 14 patients (32%) met criteria for treatment
      response and six others (14%) were partial responders. Thus, 20 patients (45%)
      were at least partial responders at long-term follow-up after one or more
      cingulotomies. Few adverse effects were reported. CONCLUSIONS: Thirty-two percent
      to 45% of patients previously unresponsive to medication and behavioral
      treatments for OCD were at least partly improved after cingulotomy. Cingulotomy
      remains a viable treatment option for patients with severe treatment-refractory
      OCD.

PMID- 11823271
TI  - Functional impairment in patients with schizotypal, borderline, avoidant, or
      obsessive-compulsive personality disorder.
AB  - OBJECTIVE: The purpose of this study was to compare psychosocial functioning in
      patients with schizotypal, borderline, avoidant, or obsessive-compulsive
      personality disorder and patients with major depressive disorder and no
      personality disorder. METHOD: Patients (N=668) were recruited by the four
      clinical sites of the Collaborative Longitudinal Personality Disorders Study. The
      carefully diagnosed study groups were compared on an array of domains of
      psychosocial functioning, as measured by the Longitudinal Interval Follow-Up
      Evaluation--Baseline Version and the Social Adjustment Scale. RESULTS: Patients
      with schizotypal personality disorder and borderline personality disorder were
      found to have significantly more impairment at work, in social relationships, and
      at leisure than patients with obsessive-compulsive personality disorder or major
      depressive disorder; patients with avoidant personality disorder were
      intermediate. These differences were found across assessment modalities and
      remained significant after covarying for demographic differences and comorbid
      axis I psychopathology. CONCLUSIONS: Personality disorders are a significant
      source of psychiatric morbidity, accounting for more impairment in functioning
      than major depressive disorder alone.

PMID- 11823273
TI  - A factor analysis of tic symptoms in Gilles de la Tourette's syndrome.
AB  - OBJECTIVE: Gilles de la Tourette's syndrome is a well-characterized disorder with
      clear DSM-IV criteria. However, the great deal of clinical variability across
      patients may represent an underlying etiologic complexity. Issues of phenotypic
      heterogeneity are particularly critical to current efforts at mapping genes
      involved in this syndrome. METHOD: Lifetime tic symptom data were obtained from
      direct structured interviews of 85 Tourette's disorder probands. Information on
      29 tic symptoms was elicited. The probands' tic symptoms were grouped by using
      agglomerative hierarchical clustering, with no a priori assumptions concerning
      the relatedness of symptoms. Scores for the probands' symptom clusters were used
      as variables in a principal-component factor analysis. The relationships of the
      resulting factor scores to comorbidity in probands and recurrence risks in
      relatives were examined. In addition, intraclass correlations were calculated for
      within-family factor scores of 36 families. RESULTS: Four significant factors
      were identified: 1) aggressive phenomena (e.g., kicking, temper fits,
      argumentativeness), 2) purely motor and phonic tic symptoms, 3) compulsive
      phenomena (e.g., touching of others or objects, repetitive speech, throat
      clearing), and 4) tapping and absence of grunting. Analysis of the symptom
      loadings, comorbidity, recurrence risks, and within-family correlations indicate
      that these factors represent a valid structure with clinical and biological
      relevance. CONCLUSIONS: In this symptom-based factor analysis of Tourette's
      disorder, four factors accounted for 61% of the phenotypic symptom variance in
      Tourette's disorder probands and their first-degree relatives. Three of these
      factors may indicate the presence of heritable components of the Tourette's
      disorder phenotype.

PMID- 11823272
TI  - Confirmatory factor analysis of DSM-IV criteria for borderline personality
      disorder: findings from the collaborative longitudinal personality disorders
      study.
AB  - OBJECTIVE: This study tested the factor structure of the DSM-IV criteria for
      borderline personality disorder by using confirmatory methods for the analysis of
      covariance structures in a large group from a multisite study. METHOD: A total of
      668 primarily treatment-seeking subjects were reliably assessed for personality
      disorders by using the Diagnostic Interview for DSM-IV Personality Disorders.
      Associations among criteria for borderline personality disorder were examined. A
      confirmatory factor analysis was performed to test diagnosis as a unitary
      construct and to test an earlier-reported three-factor model comprising disturbed
      relatedness, behavioral dysregulation, and affective dysregulation. The three
      factor model was subsequently tested by using a subset (N=498) of the study group
      that was reassessed 2 years later by independent evaluators who were blind to
      original diagnoses. RESULTS: Internal consistency of the borderline personality
      disorder diagnosis was adequate for both baseline and follow-up assessments. A
      confirmatory factor analysis model testing the borderline personality disorder
      diagnosis as a unitary construct provided good fit, and the three-factor model
      offered a significantly better fit for the baseline assessment. The three-factor
      model was replicated with the 2-year follow-up data. CONCLUSIONS: The diagnostic
      criteria for borderline personality disorder appear to reflect a statistically
      coherent construct. Three homogeneous components were supported empirically,
      lending conceptual clarity to different classes of the criteria for borderline
      personality disorder.

PMID- 11823275
TI  - Impaired recognition of facial emotion in mania.
AB  - OBJECTIVE: Recognition of facial emotion was examined in manic subjects to
      explore whether aberrant interpersonal interactions are related to impaired
      perception of social cues. METHOD: Manic subjects with bipolar I disorder (N=8),
      euthymic subjects with bipolar I (N=8) or bipolar II (N=8) disorder, and healthy
      comparison subjects (N=10) matched pictures of faces to the words "fear,"
      "disgust," "anger," "sadness," "surprise," and "happiness." RESULTS: The manic
      subjects showed worse overall recognition of facial emotion than all other
      groups. They showed worse recognition of fear and disgust than the healthy
      subjects. The euthymic bipolar II disorder subjects showed greater fear
      recognition than the manic and euthymic bipolar I disorder subjects. CONCLUSIONS:
      Impaired perception of facial emotion may contribute to behaviors in mania.
      Impaired recognition of fear and disgust, with relatively preserved recognition
      of other basic emotions, contrasts with findings for depression and is consistent
      with a mood-congruent positive bias.

PMID- 11823274
TI  - Higher prevalence of antibodies to Borrelia burgdorferi in psychiatric patients
      than in healthy subjects.
AB  - OBJECTIVE: Borrelia burgdorferi infection can affect the CNS and mimic
      psychiatric disorders. It is not known whether Borrelia burgdorferi contributes
      to overall psychiatric morbidity. The authors compared the prevalence of
      antibodies to Borrelia burgdorferi in groups of psychiatric patients and healthy
      subjects to find out whether there is an association between this infection and
      psychiatric morbidity. METHOD: Between 1995 and 1999 the authors screened for
      antibodies to Borrelia burgdorferi in 926 psychiatric patients consecutively
      admitted to Prague Psychiatric Center. They compared the results of this
      screening with findings from 884 consecutive healthy subjects who took part in an
      epidemiological survey of antibodies to Borrelia burgdorferi in the general
      population of the Czech Republic. Sera were tested by means of enzyme-linked
      immunosorbent assay. Circulating immune complexes were isolated by polyethylene
      glycol precipitation. To control for potential confounders, the two groups of
      patients and healthy subjects were matched according to gender and age. Results
      were obtained in a sample of 499 matched pairs. RESULTS: Among the matched pairs,
      166 (33%) of the psychiatric patients and 94 (19%) of the healthy comparison
      subjects were seropositive in at least one of the four assays. CONCLUSIONS: These
      findings support the hypothesis that there is an association between Borrelia
      burgdorferi infection and psychiatric morbidity. In countries where this
      infection is endemic, a proportion of psychiatric inpatients may be suffering
      from neuropathogenic effects of Borrelia burgdorferi.

PMID- 11823276
TI  - Limbic hyperreactivity in bipolar II disorder.
AB  - OBJECTIVE: The authors' goal was to determine whether patients with bipolar II
      disorder had altered regional brain responses to novel motor sequences. METHOD:
      Regional cerebral blood flow was measured with positron emission tomography in 13
      patients with bipolar II disorder and 14 healthy comparison subjects.
      Participants performed a serial reaction time task in which they were visually
      cued to press one of four buttons at a time. The order of button presses was
      determined by a complex sequence that was changed in the latter half of the
      study. RESULTS: In the comparison subjects a spatial attention circuit in the
      superior parietal lobe and supplementary motor area was activated in response to
      the introduction of the new sequence. Patients did not display this activation
      pattern; instead, a widespread limbic network was activated in response to the
      new sequence. CONCLUSIONS: The attentional resources of patients with bipolar II
      disorder are not reallocated when they are confronted with a nonemotional motor
      task; rather, their performance is altered through activation of limbic
      circuitry.

PMID- 11823277
TI  - Age at onset, childhood psychopathology, and 2-year outcome in psychotic bipolar
      disorder.
AB  - OBJECTIVE: The relationships of age at onset and childhood psychopathology to 2
      year clinical and functional outcomes in first-admission patients with bipolar I
      disorder were examined. METHOD: Patients with bipolar I disorder (N=123)
      presenting with psychotic symptoms were followed over a 2-year period. Age at
      onset was stratified into <19 and >or=19 years. Childhood psychopathology was
      categorized as behavior problems, other psychopathology, and none. Functional and
      clinical outcomes were rated with standard measures. RESULTS: Childhood
      psychopathology and age at onset were independently related to poorer functional
      and clinical outcome. In the multivariate models that included psychopathology,
      age at onset, sex, and education, early age at onset was related to incomplete
      remission, and childhood psychopathology was related to functional outcome.
      CONCLUSIONS: Childhood psychopathology and age at onset contribute independently
      to outcomes of bipolar disorder. Childhood psychopathology is a much stronger
      predictor of functioning than age at onset.

PMID- 11823278
TI  - Unaltered dopamine transporter availability in adult attention deficit
      hyperactivity disorder.
AB  - OBJECTIVE: The authors examined whether patients with attention deficit
      hyperactivity disorder (ADHD) have altered striatal dopamine transporter levels,
      which may explain psychostimulant effects in this disorder. METHOD: Single photon
      emission computed tomography and [(123)I]2beta-carbomethoxy-3beta-(4
      iodophenyl)tropane ([(123)I]beta-CIT) were used to assess dopamine transporter
      availability in nine adult patients with ADHD (eight of whom were stimulant
      naive) and nine age- and gender-matched healthy comparison subjects. RESULTS:
      Striatal [(123)I]beta-CIT binding did not differ significantly between the ADHD
      and comparison subjects. CONCLUSIONS: The findings suggest that a hypothesized
      dysregulation of dopamine function in ADHD does not entail altered dopamine
      transporter levels.

PMID- 11823279
TI  - Limited disclosure of sexual abuse in children whose experiences were documented
      by videotape.
AB  - OBJECTIVE: The authors describe obstacles to children's disclosure of their
      sexual abuse experiences. METHOD: Ten children's descriptions of 102 incidents of
      sexual abuse and the process of disclosing these incidents during police
      interviews were studied. Children's self-reports of the abuse were compared to
      videotapes of the incidents made by the lone perpetrator. RESULTS: There was a
      significant tendency among the children to deny or belittle their experiences.
      Some children simply did not want to disclose their experiences, some had
      difficulties remembering them, and one child lacked adequate concepts to
      understand and describe them. CONCLUSIONS: Failure by children to disclose their
      experiences of sexual abuse might have diverse explanations. Professionals will
      most likely never be able to identify all cases of sexual abuse on the basis of
      children's narratives.

PMID- 11823280
TI  - Transcranial magnetic stimulation for panic.

PMID- 11823281
TI  - Clozapine-induced stuttering and seizures.

PMID- 11823282
TI  - Nortriptyline for depression and vulvodynia.

PMID- 11823283
TI  - Clozapine for first-episode schizophrenia.

PMID- 11823284
TI  - Suicide attempt after use of herbal diet pill.

PMID- 11823285
TI  - Mania in hyperandrogenism, insulin resistance, and nigricans acanthosis syndrome.

PMID- 11823286
TI  - Use of dreams by psychopharmacologists.

PMID- 11823287
TI  - Pramipexole for depression.

PMID- 11823288
TI  - Antistreptolysin-O titers: implications for adult PANDAS. Pediatric autoimmune
      neuropsychiatric disorders associated with streptococcal infections.

PMID- 11823290
TI  - Benzodiazepine discontinuation in generalized anxiety disorder.

PMID- 11823292
TI  - Quetiapine and cataracts.

PMID- 11823293
TI  - Early onset of schizophrenia.

PMID- 11823294
TI  - Clozapine and suicide.

PMID- 11823295
TI  - Clozapine and suicide.

PMID- 11823296
TI  - Clozapine and dopamine D(2) blockade.

PMID- 11823298
TI  - Outcome of Asperger's syndrome.

PMID- 11823314
TI  - Old age psychiatry.

PMID- 11823315
TI  - Cortisol, serotonin and depression: all stressed out?

PMID- 11823316
TI  - Psychiatrists in the UK do not use outcomes measures. National survey.

PMID- 11823317
TI  - Patient adherence in the treatment of depression.
AB  - BACKGROUND: Non-adherence with antidepressant treatment is very common.
      Increasing adherence to pharmacological treatment may affect response rate. AIMS:
      To review and summarise quantitative evidence on factors associated with
      adherence and of adherence-enhancing interventions. METHOD: A systematic review
      of computerised databases was carried out to identify quantitative studies of
      adherence in depression. Papers retained addressed unipolar depression and
      considered adherence as the primary end-point. RESULTS: Of studies published
      between 1973 and 1999, 32 met the review criteria: epidemiological descriptive
      studies (n=14): non-random comparisons of control and intervention groups (n=3);
      randomised interventions (n=14); and meta-analysis (n=1). Patient education and
      medication clinics were the interventions most commonly tested, combined with a
      variety of other interventions. CONCLUSIONS: The studies did not give consistent
      indications of which interventions may be effective. Carefully designed clinical
      trials are needed to clarify the effect of single and combined interventions.

PMID- 11823318
TI  - The distinction between personality disorder and mental illness.
AB  - BACKGROUND: Proposals by the UK Government for preventive detention of people
      with 'dangerous severe personality disorders' highlight the unresolved issue of
      whether personality disorders should be regarded as mental illnesses. AIMS: To
      clarify the issue by examining the concepts of psychopathy and personality
      disorder, the attitudes of contemporary British psychiatrists to personality
      disorders, and the meaning of the terms 'mental illness' and 'mental disorder'.
      METHOD: The literature on personality disorder is assessed in the context of four
      contrasting concepts of illness or disease. RESULTS: Whichever of the four
      concepts or definitions is chosen, it is impossible to conclude with confidence
      that personality disorders are, or are not, mental illnesses; there are
      ambiguities in the definitions and basic information about personality disorders
      is lacking. CONCLUSIONS: The historical reasons for regarding personality
      disorders as fundamentally different from mental illnesses are being undermined
      by both clinical and genetic evidence. Effective treatments for personality
      disorders would probably have a decisive influence on psychiatrists' attitudes.

PMID- 11823319
TI  - Old age psychiatry and the law.
AB  - BACKGROUND: Old age psychiatry is no less subject to increasing legal and
      quasilegal restraint than other branches of the profession, but the emphases are
      different. Two themes predominate: first, that of capacity or competence; and
      second, to what extent formal legal measures should be implemented in cases where
      incapacitated patients do not dissent from, as opposed to giving active consent
      to, admission to hospital or receiving treatment. AIMS: To discuss the issues of
      capacity or competence, especially in relation to recent legislation and
      judgements and to proposed legislation in England and Wales. METHOD: Selective
      review and discussion of recent case law and current and proposed statute law.
      RESULTS AND CONCLUSIONS: The Bournewood case threatened but ultimately failed to
      upset the status quo. However, the European Convention on Human Rights and the
      British Human Rights Act 1998 may yet do so.

PMID- 11823320
TI  - Costs and cognitive disability: modelling the underlying associations.
AB  - BACKGROUND: The high support needs of elderly people with cognitive disability
      raise questions about the cost-effectiveness of different treatments.
      Associations between costs and cognitive disability could be influenced by other
      factors, particularly comorbidities. AIMS: To examine the links between costs and
      cognitive disability in the context of covariates. METHOD: Secondary analyses of
      data from the UK Office of Population Censuses and Surveys disability surveys for
      over 4500 elderly people living in households were used to examine associations
      between cost and cognitive disability. RESULTS: Costs varied considerably, and
      were associated with severity of disability along a number of dimensions. The
      cost-raising effects of cognitive disability were smaller when the analyses
      controlled for levels of disability in other domains. CONCLUSIONS: Cognitive
      disability is significantly associated with higher costs, but these analyses
      highlight the need to examine a range of disabilities.

PMID- 11823321
TI  - Frail old people at the margins of care: some recent research findings.
AB  - BACKGROUND: Community-based care at the margin is a substitute for institutional
      care. Three factors are considered critical: definitions of eligibility,
      assessment procedures and balance of care. AIMS: To examine determinants of the
      margin between institutional and home-based care, review current practice,
      identify the implications and contribute to planning of integrated long-term care
      services. METHOD: A selective review was made of findings from research conducted
      after the community care reforms. RESULTS: Marked variability and inconsistency
      in eligibility and assessment processes may contribute to misplacement of frail
      older people. There remains capacity to shift the balance of care from
      institutional to home-based care within reasonable cost parameters, particularly
      with more integrated services. CONCLUSIONS: Greater standardisation of approaches
      to the determination of eligibility for social care and to assessment of need is
      required. Providing care at home for some of those currently entering care homes
      is feasible, but will require different service structures and staff roles,
      including specialist clinicians.

PMID- 11823322
TI  - Genotype and phenotype in Alzheimer's disease.
AB  - BACKGROUND: Patients with Alzheimer's disease show a wide variation in clinical
      phenotype. Genetic research has been largely concerned with the role of mutations
      or common variants as risk factors for the disease. Do genetic factors also
      influence clinical phenotype? AIMS: To examine the evidence that genetic factors
      influence the clinical expression of the disease in addition to influencing risk.
      METHOD: A selective review was made of the key literature. RESULTS: Mutations in
      three genes, coding for amyloid precursor protein, presenilin-1 and presenilin-2,
      and a common variation (epsilon4) in another gene, APOE, have been shown to lead
      to an earlier development of the disease. More recently, genetic association and
      twin studies have suggested a role for genetic factors in the development of
      other aspects of clinical phenotype, notably the appearance of non-cognitive
      symptoms. CONCLUSIONS: In Alzheimer's disease genetic variation influences a
      number of aspects of clinical phenotype.

PMID- 11823323
TI  - New drugs for Alzheimer's disease and other dementias.
AB  - BACKGROUND: Alzheimer's disease management involves symptomatic drug treatments
      passed by the National Institute for Clinical Excellence. Disease modification is
      now the goal. AIMS: To review current and developmental drugs for Alzheimer's
      disease, their usage, and the clinical context of known facts and proposed
      specific models. METHOD: A brief evidence-based review was made, using literature
      where available, or evidence from consensus groups where it was absent. RESULTS:
      There is good evidence to support the use of cholinesterase inhibitors, and
      perhaps vitamin E. Oestrogen and anti-inflammatory agents show possibility, but
      there is not enough evidence to support routine use. CONCLUSIONS: Symptomatic
      treatments exist for Alzheimer's disease. Observational studies and increasing
      knowledge of brain biology are leading towards further treatment options. Old age
      psychiatrists have valuable treatments they now have to learn to use.

PMID- 11823324
TI  - Frontotemporal dementia.
AB  - BACKGROUND: Frontotemporal dementia accounts for up to 20% of cases of dementia
      in the presenium, yet remains poorly recognised. Diagnostic criteria have been
      devised to aid clinical diagnosis. AIMS: To provide an overview of clinical and
      pathological characteristics of frontotemporal dementia and its nosological
      status. METHODS: The review summarises consensus diagnostic criteria for
      frontotemporal dementia and draws on the authors' clinical experience of 300
      frontotemporal dementia cases, and pathological experience of 50 autopsied cases.
      RESULTS: Frontotemporal dementia is characterised by pronounced changes in affect
      and personal and social conduct. Some patients also develop motor neuron disease.
      Mutations in the tau gene account for some but not all familial cases of
      frontotemporal dementia. CONCLUSIONS: Frontotemporal dementia is a focal form of
      dementia, which is clinically and pathologically distinct from other dementias.
      It represents an important model for understanding the functions of the
      frontotemporal lobes.

PMID- 11823325
TI  - Dementia with Lewy bodies.
AB  - BACKGROUND: Dementia with Lewy bodies (DLB) is a common dementia subtype that has
      only been recognised in the past decade and that remains widely underdiagnosed.
      AIMS: To review the pathological and clinical features of DLB, to consider
      methods of investigation and diagnosis, and to recommend safe and effective
      management strategies. METHOD: A selective review was made of the key literature.
      RESULTS: Using operationalised criteria, DLB can be clinically diagnosed with an
      accuracy similar to that achieved for Alzheimer's disease or Parkinson's disease.
      Underdetection is largely due to poor definition of the criterion of cognitive
      fluctuation. Ancillary investigations, particularly neuroimaging, can aid in
      differential diagnosis. Extreme caution in the use of neuroleptic medication is
      advised. Cholinesterase inhibitors may be particularly effective in DLB.
      CONCLUSIONS: Clinicians should be aware of DLB as part of a spectrum of Lewy body
      disorders. Neuroleptic sensitivity reactions and good response to cholinergic
      therapies are important aspects of management.

PMID- 11823326
TI  - Subcortical dementia.
AB  - BACKGROUND: Drawing a distinction between cortical and subcortical dementias
      seems both useful and justified. Recent research has, however, cast doubt on the
      clinical, neuropsychological, neuroimaging and neuroanatomical basis of the
      distinction. AIMS: To arrive at a reasoned conclusion about the relationship
      between the two types of dementia and the validity of distinguishing between
      them. METHOD: The historical and recent clinical and scientific literature on
      subcortical dementia was reviewed. RESULTS: The traditional claim that
      subcortical dementia has distinct clinical manifestations, neuroimaging findings
      and a neuropathological profile is not altogether borne out by the literature.
      Some studies show that frontal executive dysfunction and the profile of memory
      deficits are not significantly different from those seen in Alzheimer's disease.
      Neuropathological findings also overlap. CONCLUSIONS: The category of subcortical
      dementia may be clinically useful in highlighting the likelihood that an
      individual with dementia is more likely to suffer from bradyphrenia and motor
      difficulties. As neuroscience advances a preoccupation with the distinction may
      hinder the assessment and treatment of individual cases.

PMID- 11823327
TI  - Vascular dementia: a diagnosis running out of time.
AB  - BACKGROUND: The concept of vascular dementia has a long history but its
      usefulness as a diagnostic category has been called into question. AIMS: To
      evaluate vascular disease as a risk factor for dementia and the interface between
      cerebrovascular pathology and Alzheimer's disease. METHOD: The literature on this
      topic was selectively reviewed and synthesised. RESULTS: Risk factors for
      cerebrovascular disease are also risk factors for dementia. However, the course
      of dementia, once it has developed, appears to be frequently determined by
      Alzheimer's disease. CONCLUSIONS: As a public health measure, modification of
      vascular risk represents a potentially powerful means to prevent dementia through
      delaying its onset. However, an effect on progression of dementia, once it has
      developed, has yet to be established. The traditional view of vascular dementia
      and Alzheimer's disease as distinguishable conditions is becoming steadily less
      tenable.

PMID- 11823328
TI  - Vascular basis of late-onset depressive disorder.
AB  - BACKGROUND: Growing evidence suggests that there may be a subtype of depression
      arising in later life that is characterised by a distinct clinical presentation
      and an association with cerebrovascular disease. This has been termed 'vascular
      depression'. AIMS: To review the evidence for associations between cardiovascular
      disease and depression and between cerebrovascular disease and depression, and to
      examine implications for clinical practice and research. METHOD: The authors
      reviewed the medical literature covering the past 5 years. RESULTS: There is
      strong evidence for an association between cardiovascular disease and depression,
      but this is not confined to older people. The causal pathway may be bi
      directional. There is also a convergence of evidence suggesting a causal link
      between cerebrovascular disease and depression, especially that occurring later
      in life. The major focus has been on neuroradiological findings thought to be due
      to vascular disease, although the pathology may be heterogeneous. CONCLUSIONS:
      Although there are gaps in the evidence there is strong support for the concept
      of vascular depression, characterised by reduced depression ideation, subcortical
      neurological dysfunction, apathy and psychomotor change. This has implications
      for both treatment and prevention.

PMID- 11823329
TI  - Rating scales in old age psychiatry.
AB  - BACKGROUND: There is a vast array of scales available to assess all aspects of
      mental and physical health in older people which may be of relevance to the work
      of old age psychiatrists. AIMS: To summarise some of the scales that may be
      commonly used in clinical and research practice and to give the reader guidelines
      as to where further information can be obtained. METHOD: The scales were selected
      on the basis of the authors' own clinical and research knowledge and information
      was gathered from a comprehensive text on assessment scales in old age
      psychiatry. Results The selected scales are described in brief and a table
      outlines the purposes for which they are most suitable. CONCLUSIONS: Although
      many scales are available, the choice of the individual scale relies specifically
      on the question that is to be asked. The ideal scale does not exist.

PMID- 11823330
TI  - Bio-social origins of depression in the community. Interactions between social
      adversity, cortisol and serotonin neurotransmission.
AB  - BACKGROUND: Social adversity may be a risk factor for depression, by increasing
      cortisol secretion, which impairs serotonin (5-HT) neurotransmission. AIMS: To
      examine this causal pathway in a community setting. METHOD: Women who were
      currently ICD-10 depressed (n=94), vulnerable to depression but not depressed
      (n=166) and non-vulnerable controls (n=177) were recruited. We assessed social
      adversity and vulnerability (Life Events and Difficulties Schedule; Self
      Evaluation and Social Support Scales) and psychiatric state (Schedules for
      Clinical Assessment in Neuropsychiatry). Salivary cortisol concentrations were
      measured at 09.00 and 23.00 h. Serotonin function was assessed using prolactin
      responses to dexfenfluramine. RESULTS: Cortisol concentrations were not increased
      in the depressed or vulnerable. Morning salivary and serum cortisol were reduced
      in depression. Evening cortisol was increased after recent life events. Life
      events and depression were associated with increased prolactin responses.
      CONCLUSIONS: The hypothalamic-pituitary-adrenal axis is sensitive to social
      stress but does not mediate vulnerability to depression. Exaggerated 5-HT(2)
      receptor responsiveness to stress may play a role in the evolution of depression.

PMID- 11823331
TI  - Occurrence of hallucinatory experiences in a community sample and ethnic
      variations.
AB  - BACKGROUND: Hallucinations typically are associated with severe psychiatric
      illness but also are reported by individuals with no psychiatric history. AIMS:
      To examine the prevalence of hallucinations in White and ethnic minority samples
      using data from the Fourth National Survey of Ethnic Minorities. METHOD:
      Interviews of 5196 ethnic minority and 2867 White respondents were carried out.
      The respondents were screened for mental health problems and the Psychosis
      Screening Questionnaire asked about hallucinations. Those who screened positive
      underwent a validation interview using the Present State Examination. RESULTS:
      Four per cent of the White sample endorsed a hallucination question.
      Hallucinations were 2.5-fold higher in the Caribbean sample and half as common in
      the South Asian sample. Of those who reported hallucinatory experiences, only 25%
      met the criteria for psychosis. CONCLUSIONS: The results provide an estimate of
      the annual prevalence of hallucinations in the general population. The variation
      across ethnic groups suggests cultural differences in these experiences.
      Hallucinations are not invariably associated with psychosis.

PMID- 11823332
TI  - Schizotypal components in people at high risk of developing schizophrenia: early
      findings from the Edinburgh High-Risk Study.
AB  - BACKGROUND: The study of high-risk groups and the development of schizophrenia.
      AIMS: To investigate further schizotypy, measured by the Structured Interview for
      Schizotypy (SIS), and to examine relationships between schizotypal components,
      psychotic symptoms on the Present State Examination (PSE) and subsequent
      schizophrenia. METHOD: The SIS and PSE were administered on entry. Schizophrenia
      onsets were recorded during follow-up. RESULTS: The SIS yielded four principal
      components labelled social withdrawal, psychotic symptoms, socio-emotional
      dysfunction and odd behaviour. On entry, these differentiated between controls,
      subjects at risk for schizophrenia with and without symptoms and patients with
      schizophrenia. Seven of 78 subjects at risk developed schizophrenia within 39
      months. This was best predicted by combining the four SIS components.
      CONCLUSIONS: Schizotypy is heterogeneous and may become psychosis, particularly
      if several of its components are present. As psychosis develops, odd behaviour
      gives way to psychotic symptoms and social function deteriorates.

PMID- 11823333
TI  - Reporting of randomised trials.

PMID- 11823334
TI  - Genetic research on cognitive ability.

PMID- 11823335
TI  - Attitudes to depot antipsychotics.

PMID- 11823337
TI  - Stigma, suicide and religion.

PMID- 11823336
TI  - Schizophrenia-like psychosis in African and Caribbean elders.

PMID- 11823338
TI  - Depot injections and nut allergy.

PMID- 11823340
TI  - Other approaches to mental and physical illness.

PMID- 11823342
TI  - Winter vomiting.

PMID- 11823343
TI  - Hyperprolactinaemia caused by antipsychotic drugs.

PMID- 11823344
TI  - Long waiting lists in hospitals.

PMID- 11823345
TI  - Preventing domestic violence.

PMID- 11823347
TI  - French healthcare system beset by strikes.

PMID- 11823348
TI  - Advocates of PSA testing campaign to silence critics.

PMID- 11823349
TI  - Doctor says some hospitals too ready to apologise.

PMID- 11823350
TI  - Pro-tobacco writer admits he should have declared an interest.

PMID- 11823351
TI  - Academics face court clash with tobacco giants.

PMID- 11823352
TI  - Gujarat earthquake causes major mental health problems.

PMID- 11823353
TI  - Withdrawal from paroxetine can be severe, warns FDA.

PMID- 11823354
TI  - WHO issues guidance on monitoring injuries.

PMID- 11823355
TI  - Mortality and volume of cases in paediatric cardiac surgery: retrospective study
      based on routinely collected data.
AB  - OBJECTIVES: To determine whether mortality between 1991 and 1995 in hospitals in
      England carrying out surgery for congenital heart disease in children was
      associated with the annual volume of cases and to estimate the extent to which an
      association could explain the apparent divergent mortality at Bristol Royal
      Infirmary. DESIGN: Retrospective analysis of data from two sources, a register of
      returns by surgeons to their professional society and an administrative database.
      SETTING: 12 hospitals in England carrying out surgery for congenital heart
      disease over the period April 1991 to March 1995. MAIN OUTCOME MEASURE: 30 day
      mortality. RESULTS: For open heart operations in children under 1 year old, and
      in particular for arterial switches and repair of atrioventricular septal defect,
      there is strong and consistent evidence of an inverse association between
      mortality and volume of cases (not taking into account any data from Bristol). A
      hospital carrying out 120 open operations per year in 1991-5 on children aged
      under 1 year would be expected to have a mortality 25% lower than that in a
      hospital carrying out 40 operations. If the children in the hospitals had the
      same mix of operations, this reduction is 34%. Stratifying for types of operation
      or including the results from Bristol strengthens this association. It was also
      estimated that less than a fifth of the excess mortality at Bristol Royal
      Infirmary in open operations in children less than 1 year old was due to the
      hospital's lower volume of surgery. CONCLUSIONS: Using appropriate methods, this
      study showed that mortality in paediatric cardiac surgery was inversely related
      to the volume of surgery. Considerable caution is needed in interpreting these
      results, and it does not necessarily follow that concentrating resources in fewer
      centres would reduce mortality.

PMID- 11823357
TI  - Improvement in cholesterol emboli syndrome after iloprost therapy.

PMID- 11823356
TI  - Relative importance of genetic effects in rheumatoid arthritis: historical cohort
      study of Danish nationwide twin population.
AB  - OBJECTIVE: To determine the relative importance of environmental and genetic
      effects in the development of rheumatoid arthritis. DESIGN: Historical cohort
      study with record linkage between a twin registry and the Danish discharge
      registry as well as the Danish national registry of deaths used to estimate
      completeness. SETTING: Two population based nationwide twin birth cohorts.
      PARTICIPANTS: 37 338 twins were sent a questionnaire about rheumatic diseases.
      Self reported rheumatoid arthritis was verified by clinical examination and from
      medical records. MAIN OUTCOME MEASURES: The probandwise concordance rate of
      rheumatoid arthritis in monozygotic and dizygotic twins. RESULTS: The response
      rate was 84.7%. Rheumatoid arthritis was verified in 13 monozygotic and 36
      dizygotic twins. There were no concordant monozygotic twin pairs and two
      concordant dizygotic twin pairs. Based on capture-recapture methods the
      probability of ascertainment was 78.3%. The probandwise concordance rate was 0
      (95% confidence interval 0 to 24.7) in monozygotic twins and 8.8 (1.9 to 23.7) in
      dizygotic twins. CONCLUSION: Genes are of minor importance in the development of
      rheumatoid arthritis.

PMID- 11823358
TI  - Challenges in managing profound hypokalaemia.

PMID- 11823359
TI  - Reported frequency of domestic violence: cross sectional survey of women
      attending general practice.
AB  - OBJECTIVES: To determine exposure to violence by a partner or spouse among women
      attending general practice and its association with respondents' demographic and
      personal characteristics; frequency of inquiry about violence by general
      practitioners; and women's views on routine questioning about domestic violence
      by general practitioners. DESIGN: Cross sectional, self administered, anonymous
      survey. SETTING: 22 volunteer Irish general practices. PARTICIPANTS: 1871 women
      attending general practice. MAIN OUTCOME MEASURES: Proportion who had experienced
      domestic violence, severity of such violence, and context in which violence
      occurred. RESULTS: Of the 1692 women who had ever had a sexual relationship, 651
      (39%, 95% confidence interval 36% to 41%) had experienced violent behaviour by a
      partner. 78/651 (12%) women reported that their doctor had asked about domestic
      violence. 298/651 (46%, 42% to 50%) women had been injured, 60 (20%) of whom
      reported that their doctor had asked about domestic violence. 1304/1692 (77%, 77%
      to 80%) were in favour of routine inquiry about domestic violence by their usual
      general practitioner. 1170 women (69%) reported controlling behaviour by their
      partner and 475 (28%) reported feeling afraid of their previous or current
      partner. Women who reported domestic violence were 32 times more likely to be
      afraid of their partner than women who did not report such violence. CONCLUSIONS:
      Almost two fifths of women had experienced domestic violence but few recalled
      being asked about it. Most women favoured routine questioning by their
      practitioner about such violence. Asking women about fear of their partner and
      controlling behaviour may be a useful way of identifying those who have
      experienced domestic violence.

PMID- 11823360
TI  - Identifying domestic violence: cross sectional study in primary care.
AB  - OBJECTIVES: To measure the prevalence of domestic violence among women attending
      general practice; test the association between experience of domestic violence
      and demographic factors; evaluate the extent of recording of domestic violence in
      records held by general practices; and assess acceptability to women of screening
      for domestic violence by general practitioners or practice nurses. DESIGN: Self
      administered questionnaire survey. Review of medical records. SETTING: General
      practices in Hackney, London. PARTICIPANTS: 1207 women (>15 years) attending
      selected practices. MAIN OUTCOME MEASURES: Prevalence of domestic violence
      against women. Association between demographic factors and domestic violence
      reported in questionnaire. Comparison of recording of domestic violence in
      medical records with that reported in questionnaire. Attitudes of women towards
      being questioned about domestic violence by general practitioners or practice
      nurses. RESULTS: 425/1035 women (41%, 95% confidence interval 38% to 44%) had
      ever experienced physical violence from a partner or former partner and 160/949
      (17%, 14% to 19%) had experienced it within the past year. Pregnancy in the past
      year was associated with an increased risk of current violence (adjusted odds
      ratio 2.11, 1.39 to 3.19). Physical violence was recorded in the medical records
      of 15/90 (17%) women who reported it on the questionnaire. At least 202/1010
      (20%) women objected to screening for domestic violence. CONCLUSIONS: With the
      high prevalence of domestic violence, health professionals should maintain a high
      level of awareness of the possibility of domestic violence, especially affecting
      pregnant women, but the case for screening is not yet convincing.

PMID- 11823361
TI  - Influence of direct to consumer pharmaceutical advertising and patients' requests
      on prescribing decisions: two site cross sectional survey.

PMID- 11823362
TI  - Booked inpatient admissions and hospital capacity: mathematical modelling study.
AB  - OBJECTIVES: To investigate the variability of patients' length of stay in
      intensive care after cardiac surgery. To investigate potential interactions
      between such variability, booked admissions, and capacity requirements. DESIGN:
      Mathematical modelling study using routinely collected data. SETTING: A cardiac
      surgery department. SOURCE OF DATA: Hospital records of 7014 people entering
      intensive care after cardiac surgery. MAIN OUTCOME MEASURES: Length of stay in
      intensive care; capacity requirements of an intensive care unit for a
      hypothetical booked admission system. RESULTS: Although the vast majority of
      patients (89.5%) had a length of stay in intensive care of < or = 48 hours, there
      was considerable overall variability and the distribution of stays has a lengthy
      tail. A mathematical model of the operation of a hypothetical booking system
      indicates that such variability has a considerable impact on intensive care
      capacity requirements, indicating that a high degree of reserve capacity is
      required to avoid high rates of operation cancellation because of unavailability
      of suitable postoperative care. CONCLUSION: Despite the considerable enthusiasm
      for booked admissions systems, queuing theory suggests that caution is required
      when considering such systems for inpatient admissions. Such systems may well
      result in frequent operational difficulties if there is a high degree of
      variability in length of stay and where reserve capacity is limited. Both of
      these are common in the NHS.

PMID- 11823363
TI  - Childhood leukaemia.

PMID- 11823365
TI  - Chronic aspirin is effective--if data are massaged sufficiently.

PMID- 11823364
TI  - All you need is cognitive behaviour therapy?

PMID- 11823366
TI  - Revalidating retired doctors. Revalidation is essential for retired doctors who
      continue to practise.

PMID- 11823367
TI  - Transplant patients need to be made aware of skin cancer risk.

PMID- 11823368
TI  - Use of interactive multimedia decision aids. Alternative explanation for results
      may exist.

PMID- 11823369
TI  - Any changes in prevalence of autism must be determined.

PMID- 11823370
TI  - Public views of UK Population Biomedical Collection are being taken into account.

PMID- 11823371
TI  - Independent review of Worcester PFI is needed.

PMID- 11823372
TI  - Variation in rates of oestrogen receptor positivity in breast cancer again.

PMID- 11823373
TI  - Canadian Medicare needs choice.

PMID- 11823374
TI  - New method to monitor drugs at dance venues. Perhaps results of testing tablets
      should be made public.

PMID- 11823375
TI  - Widespread body pain and mortality. Theories that psychological states cause
      cancer should be rejected.

PMID- 11823376
TI  - Evaluation is essential for all types of intervention.

PMID- 11823377
TI  - Cover picture highlighted what is wrong with approach to managing chronic
      disease.

PMID- 11823378
TI  - Emergency departments are well placed to identify alcohol misuse problems.

PMID- 11823379
TI  - Reducing health risks to British Muslim pilgrims.

PMID- 11823381
TI  - Working in the European Union.

PMID- 11823380
TI  - Hand-arm vibration syndrome may be associated with prolonged use of vibrating
      computer games.

PMID- 11823382
TI  - The European Computer Driving License.

PMID- 11823386
TI  - Should we use breathing filters in anesthesia?

PMID- 11823387
TI  - Prevent hypotension and hypoxemia.

PMID- 11823388
TI  - Rapid and complete occlusion of a heat and moisture exchange filter by pulmonary
      edema (clinical report).
AB  - PURPOSE: A case of near fatal obstruction of a breathing system is described, due
      to occlusion of a heat and moisture exchange filter in a patient with pulmonary
      edema. Previous reports have described cases of mechanical obstruction to fresh
      gas flow due to an accumulation of a bolus of fluid within the filter housing.
      However, in this case, the cause of occlusion was due to the protein and cell
      debris contained in a small amount of pulmonary edema fluid interacting with the
      filter membrane. CLINICAL FEATURES: Obstruction occurred rapidly and without
      warning, and was difficult to differentiate from the more common diagnoses of
      bronchospasm or tension pneumothorax. Outwardly the filter appeared normal, and
      routine protocol for emergency management of suspected breathing system
      obstruction initially failed to identify the site of occlusion. CONCLUSION:
      Minimal contamination by proteinaceous fluid may cause rapid and complete
      occlusion of a breathing system filter. Blockage of the breathing system filter
      and catheter mount should be considered in cases of unexplained breathing system
      occlusion. The use of a fresh breathing system without a filter for each patient,
      as recommended by The American Center for Disease Control and the American
      Society of Anesthesiologists, would have prevented this scenario from occurring.

PMID- 11823389
TI  - Antidepressant treatment for chronic depressed patients should not be
      discontinued prior to anesthesia.
AB  - PURPOSE: To investigate whether antidepressants administered to patients for
      chronic depression patients should be continued or discontinued before
      anesthesia. RESULTS: We studied 80 depressed patients who were scheduled to
      undergo orthopedic surgery under general anesthesia. The patients were divided
      randomly into two groups; patients in Group A (n=40) continued antidepressants
      before surgery and patients in Group B (n=40) discontinued antidepressants 72 hr
      before surgery. Two (5%) out of 40 patients in Group A and eight (20%) out of 40
      patients in Group B had deterioration of depressive symptoms (P=0.04). Delirium
      or confusion during the perioperative course occurred in five patients (13%) in
      Group A and in 12 (30%) in Group B (P=0.05). There were no significant
      differences in incidence (5 vs 6%) of hypotension and arrhythmias during
      anesthesia between the two groups. CONCLUSION: Antidepressants administered to
      depressed patients should be continued before anesthesia. Discontinuation of
      antidepressants did not increase the incidence of hypotension and arrhythmias
      during anesthesia, but increased symptoms of depression and delirium or
      confusion.

PMID- 11823390
TI  - Intraosseous lidocaine provides effective analgesia for percutaneous
      vertebroplasty of osteoporotic fractures.
AB  - PURPOSE: To assess the safety and efficacy of intraosseous lidocaine (IL), in
      comparison with iv nalbuphine and propacetamol (NP) for analgesia during
      percutaneous vertebroplasty (PV) in order to avoid general anesthesia in elderly
      patients. METHODS: Patients (age 68 +/- 13 yr, weight 66 +/- 6 kg) undergoing PV
      for osteoporotic fractures were randomized prospectively into two groups: NP
      (n=50) and IL (n=50). All patients were premedicated (oral hydroxyzine 1 mg.kg(
      1)) and had skin infiltration with 5 mL of 1% lidocaine prior to vertebral
      puncture. Thirty minutes before the procedure, Group NP received, in a blinded
      manner, 50 mL of iv nalbuphine (0.3 mg.kg(-1)) and propacetamol (30 mg.kg(-1))
      while Group IL received 50 mL of iv saline. During vertebral puncture, Groups NP
      and IL received, in a blinded manner, 1 mL.10 kg(-1) of intraosseous saline and
      1% lidocaine respectively. Pain was assessed during vertebral puncture and cement
      injection with a four-point verbal rating scale. Additionally, lidocaine plasma
      kinetics were obtained in 11 IL patients. RESULTS: Analgesic efficacy was similar
      in the IL and NP groups (85 vs 84%). Group NP had more side effects. Lidocaine
      peak recorded concentration was 2.6 +/- 0.1 microg.mL(-1) i.e., about three times
      less than the reported toxic limits. CONCLUSION: IL is as effective as the
      association of iv NP for analgesia in PV. However, considering that both
      protocols were insufficient in about 15% of cases, other modalities are needed to
      further improve analgesia and avoid general anesthesia during vertebroplasty.

PMID- 11823391
TI  - Intermittent pneumatic compression prevents venous stasis in the lower
      extremities in the lithotomy position.
AB  - PURPOSE: To investigate the interactions of a new lithotomy positioning device
      (LPD) with two intermittent pneumatic compression (IPC) devices by measuring
      femoral venous flow velocity. METHODS: Subjects were divided into three groups:
      1) supine position as a control, 2) lithotomy position using a conventional LPD,
      and 3) lithotomy position using a new LPD, Levitator(TM). These three groups were
      further divided in two according to the type of IPC device used: AV-impulse(TM)
      (rapid IPC) and SeQuel(TM) (standard IPC). Peak femoral venous flow velocity was
      measured by using an ultrasonic echo diagnostic device. Data were analyzed by one
      way ANOVA with Fisher's test or by the unpaired two-tailed t test. RESULTS:
      Moving to the conventional lithotomy position from the supine position, venous
      flow velocity was decreased by 38% in both IPC device groups. Even when the new
      LPD was used to support the lithotomy position, the flow velocity was decreased
      by 24%, but the velocity was significantly higher than in the conventional
      lithotomy position. Both rapid and standard IPC devices increased flow velocity
      to 77% and 107% (first compression) and to 71% and 84% (fifth compression) of the
      control values during compression, respectively. In the lithotomy position group
      using the new LPD, similar increases in flow were seen with the use of IPC
      devices. CONCLUSION: Both rapid and standard IPC devices are useful for
      maintaining venous flow of the lower extremities in the lithotomy position.

PMID- 11823392
TI  - Elevated vascular resistance after labetalol during resection of a
      pheochromocytoma (brief report).
AB  - PURPOSE: To report a case of pheochromocytoma exhibiting an increase in systemic
      vascular resistance index (SVRI) and decreased cardiac index (CI) after use of
      labetalol. CLINICAL FEATURES: A 36-yr-old male underwent adrenectomy for
      pheochromocytoma. Midazolam 5 mg, fentanyl 100 microg and labetalol 20 mg were
      administrated intravenously for premedication upon arrival in the operating
      theatre. After induction of anesthesia with fentanyl, thiopental and atracurium,
      30 mg iv labetalol was administered. The blood pressure gradually rose to 178/101
      mmHg with mildly increased SVRI (1958 dn-sec(-1).m(2).cm(5)) and stable CI (3.8
      L.min(-1).m(2) ). The blood pressure reached 247/150 mmHg after intubation with
      an increase in SVRI (3458 dn-sec(-1).m(2).cm(5)) and a decrease in CI (3.6 L.min(
      1).m(2)). The SVRI increased further to 4986 dn-sec(-1).m(2).cm(5) and CI
      declined to 2.4 L.min(-1).m(2) after the administration of additional labetalol
      20 mg. Sodium nitroprusside was administered and the blood pressure declined
      immediately to 108/72 mmHg, with a decreased SVRI (2526 dn-sec(-1).m(2).cm(5))
      and stable CI (2.3 L.min(-1).m(2)). CONCLUSIONS: The elevated SVRI with low CI
      was considered to result from increased alpha-adrenergic activity secondary to ss
      adrenergic blockade with labetalol. Clinicians should be aware of the possibility
      of a hypertensive crisis after iv labetalol. We suggest that labetalol should be
      replaced promptly with alpha-adrenergic blockers or other vasodilators when such
      a condition arises.

PMID- 11823393
TI  - Calcium channels--basic aspects of their structure, function and gene encoding;
      anesthetic action on the channels--a review.
AB  - PURPOSE: To review recent findings concerning Ca(2+) channel
      subtype/structure/function from electrophysiological and molecular biological
      studies and to explain Ca(2+) channel diseases and the actions of anesthetics on
      Ca(2+) channels. SOURCE: The information was obtained from articles published
      recently and from our published work. PRINCIPAL FINDINGS: Voltage-dependent
      Ca(2+) channels serve as one of the important mechanisms for Ca(2+) influx into
      the cells, enabling the regulation of intracellular concentration of free Ca(2+).
      Recent advances both in electrophysiology and in molecular biology have made it
      possible to observe channel activity directly and to investigate channel
      functions at molecular levels. The Ca(2+) channel can be divided into subtypes
      according to electrophysiological characteristics, and each subtype has its own
      gene. The L-type Ca(2+) channel is the target of a large number of clinically
      important drugs, especially dihydropyridines, and binding sites of Ca(2+)
      antagonists have been clarified. The effects of various kinds of anesthetics in a
      variety of cell types have been demonstrated, and some clinical effects of
      anesthetics can be explained by the effects on Ca(2+) channels. It has recently
      become apparent that some hereditary diseases such as hypokalemic periodic
      paralysis result from calcium channelopathies. CONCLUSION: Recent advances both
      in electrophysiology and in molecular biology have made it possible to clarify
      the Ca(2+) channel structures, functions, genes, and the anesthetic actions on
      the channels in detail. The effects of anesthetics on the Ca(2+) channels either
      of patients with hereditary channelopathies or using gene mutation techniques are
      left to be discovered.

PMID- 11823394
TI  - The addition of tramadol to lidocaine does not reduce tourniquet and
      postoperative pain during iv regional anesthesia.
AB  - PURPOSE: We conducted a prospective, randomized, double-blind study to determine
      whether the combination of tramadol with lidocaine 0.5% had an analgesic effect
      on tourniquet pain during iv regional anesthesia and also on postoperative pain.
      METHODS: Thirty patients scheduled for carpal tunnel decompression were included
      in the study. Each patient received 3 mg.kg(-1) of plain lidocaine 0.5% with 100
      mg of tramadol (Group T) or 2 mL of isotonic saline (Group C). The mixture was
      injected into the isolated and exsanguinated arm. Pain was assessed using a
      linear visual analog scale and a verbal rate scale during the surgical procedure
      and the postoperative period (240 min) and subsequently at interview at 24 hr.
      Analgesic consumption was recorded. RESULT: There was no difference in the pain
      scales and analgesic request at any of the time periods studied. CONCLUSION: We
      conclude, therefore, that for carpal tunnel operation under iv regional
      anesthesia, the combination of tramadol and lidocaine is not more effective than
      lidocaine alone.

PMID- 11823395
TI  - Central nervous system side effects are less important after iv regional
      anesthesia with ropivacaine 0.2% compared to lidocaine 0.5% in volunteers.
AB  - PURPOSE: Following release of a double tourniquet for intravenous regional
      anesthesia (IVRA), ropivacaine was shown to have a longer duration of action and
      less central nervous system (CNS) side effects than lidocaine. This study
      examines the correlation of CNS side effects to plasma levels of lidocaine 0.5%
      and ropivacaine 0.2% when injected intravenously for IVRA. METHODS: In a double
      blind, cross-over study, ten volunteers received IVRA with 40 mL ropivacaine 0.2%
      or lidocaine 0.5% at least four days apart. Both cuffs of a double-cuff
      tourniquet remained inflated until they could no longer be tolerated. The
      incidence, duration and intensity of CNS side effects were recorded at three,
      ten, and 30 min after tourniquet release and correlated with simultaneous venous
      blood samples. RESULTS: There was a lower incidence of CNS side effects with
      ropivacaine (6/10 volunteers) when compared to lidocaine (10/10 volunteers).
      There was also less duration of these side effects (mean +/- SD, 5.1 +/- 5.2 min
      vs 11.7 +/- 6.7 min). Measured total plasma levels were highest at ten minutes
      with ropivacaine 0.2% (1.2 +/- 0.3 microg.mL(-1)) and at three minutes with
      lidocaine 0.5% (1.7 +/- 0.6 microg.mL(-1)). Peak CNS symptoms correlated with
      measured venous plasma levels for lidocaine, but occurred earlier with
      ropivacaine. CONCLUSIONS: We observed a lower incidence of CNS side effects with
      ropivacaine as compared to lidocaine. Although ropivacaine's greater lipid
      solubility should, theoretically, lead to more CNS side effects, this was,
      likely, offset by slower release from tissues and lesser percentage of unbound
      (free) drug.

PMID- 11823396
TI  - Use of a double epidural catheter provides effective postoperative analgesia
      after spine deformity surgery.
AB  - PURPOSE: Spine deformity surgery is a painful procedure in which pain control is
      difficult to obtain. The aim of this study was to evaluate the efficacy of double
      epidural catheters in this setting. METHODS: Twenty-three patients scheduled for
      an elective spine deformity surgery were included prospectively. At the end of
      surgery, the surgeon inserted two epidural catheters, one cranial, one caudal to
      the surgical field. In the recovery room the catheters were both injected with a
      bolus of bupivacaine 0.0625%. In the absence of any neurological abnormality a
      continuous infusion of bupivacaine 0.0625%, fentanyl 2 microg.mL(-1) and
      clonidine 3 microg.mL(-1) was administered at a rate of 10 mL.hr(-1) through each
      catheter for 48 hr. Pain score, sedation level, motor block and side-effects were
      checked regularly. RESULTS: Complete analgesia (VAS=0) was obtained at rest in
      all patients. During mobilization and physiotherapy four patients (17%) had a VAS
      30. No motor block was observed. Four patients (17%) had nausea and vomiting. No
      excessive sedation, pruritus or respiratory depression were observed. Early
      mobilization was possible in all patients. CONCLUSION: Postoperative epidural
      analgesia by means of a double catheter is an effective technique to control pain
      after spine deformity surgery and is associated with a low incidence of side
      effects.

PMID- 11823397
TI  - Intrathecal carbachol and clonidine produce a synergistic antiallodynic effect in
      rats with a nerve ligation injury.
AB  - PURPOSE: Antiallodynic effects have been demonstrated after intrathecal
      administration of alpha-2 adrenoceptor agonists and cholinesterase inhibitors in
      rats. Intrathecal carbachol also increases the activity of cholinergic receptor
      system at the spinal level. However, there is no study regarding the antagonism
      of carbachol on touch-evoked allodynia and the interaction with clonidine. This
      study examines the intrathecal interaction between two drugs in a rat model of
      nerve ligation injury. METHODS: Rats were prepared with tight ligation of the
      left L5-6 spinal nerves and chronic intrathecal catheter implantation. Tactile
      allodynia was measured by using application of von Frey filaments to the lesioned
      hindpaw. Carbachol (0.3-10 microg) and clonidine (1-30 microg) were administered
      to obtain the dose-response curves and the 50% effective dose (ED(50)) for each
      drug. Fractions of ED(50) values (1/2, 1/4, 1/8, and 1/16) were administered
      intrathecally to establish the ED(50) of the carbachol-clonidine combination.
      Isobolographic and fractional analyses of drug interaction were performed.
      RESULTS: Intrathecal carbachol and clonidine alone produced a dose-dependent
      reduction of tactile allodynia without severe motor weakness or sedation. A
      carbachol-clonidine combination produced a dose-dependent increase in withdrawal
      threshold of the lesioned hindpaw with a reduced incidence and magnitude of side
      effects. Both analyses revealed a synergistic interaction after the
      coadministration of carbachol and clonidine. CONCLUSIONS: This study indicates
      that carbachol, like clonidine, provides a moderate antagonism on touch-evoked
      allodynia at the spinal level. The results suggest that intrathecally
      administered carbachol is synergistic when combined with clonidine.

PMID- 11823398
TI  - Baseline heart rate may predict hypotension after spinal anesthesia in
      prehydrated obstetrical patients.
AB  - PURPOSE: Hypotension is the most frequent complication of spinal anesthesia in
      pregnant patients. This study was designed to identify patients at risk for
      postspinal hypotension based on preoperative vital signs before and after an
      orthostatic challenge. METHODS: Forty healthy women scheduled for elective
      Cesarean section were enrolled in this prospective trial. Blood pressure (BP) and
      heart rate (HR) were recorded with the patient in the lateral supine position and
      after standing up. After a bupivacaine spinal anesthetic, BP was obtained every
      two minutes for 30 min. Ephedrine treatment was administered based on the degree
      of hypotension observed. Hemodynamic parameters were correlated to ephedrine
      requirements (Spearman's rank order correlation). RESULTS: There was a
      significant correlation in baseline maternal HR and ephedrine requirements
      (P=0.005). The degree of orthostatic changes in mean arterial BP and HR did not
      correlate with postspinal hypotension. CONCLUSIONS: Baseline HR may be predictive
      of obstetric spinal hypotension. Higher baseline HR, possibly reflecting a higher
      sympathetic tone, may be a useful parameter to predict postspinal hypotension.

PMID- 11823399
TI  - Intranasal fentanyl provides adequate postoperative analgesia in pediatric
      patients.
AB  - PURPOSE: To evaluate intranasally administered fentanyl for postoperative
      analgesia in pediatric patients. METHODS: Thirty-two children aged four to eight
      years, ASA physical status I and II were included in this prospective randomized
      controlled study. In the postoperative care unit, patients were allocated to
      receive fentanyl, using a double-blind study design, either intranasally (Group
      I) or intravenously (Group II) in small titrated doses until they became pain
      free or side effects appeared which prohibited continuation of the drug. RESULTS:
      Satisfactory analgesia was achieved in both groups, though the required drug
      dosage was higher in the intranasal group (1.43 +/- 0.39 microg.kg(-1)). Onset of
      analgesia tended to be slower via the intranasal route compared to the iv route
      (13 +/- 4.5 vs 8.3 +/- 3.08 min; P=not significant). Side effects observed in
      this series were within an acceptable range and similar for both modalities.
      CONCLUSION: The intranasal route provides a good alternative for administration
      of fentanyl in pediatric surgical patients.

PMID- 11823401
TI  - Tracheal intubation in children with Morquio syndrome using the angulated video
      intubation laryngoscope.
AB  - PURPOSE: There are a number of syndromes with proven or suspected instability of
      the cervical spine especially in pediatric patients. It is a challenge for the
      anesthesiologist to intubate these patients with as little movement of the
      cervical spine as possible. A new device to facilitate this task is the angulated
      video-intubation laryngoscope (AVIL). CLINICAL FEATURES: The AVIL is a curved
      endoscopic intubation laryngoscope with angulated distal tip. The video-view from
      the distal blade tip improves glottic visualization during difficult direct
      laryngoscopy. We report three sisters with Morquio syndrome scheduled for
      otorhinolaryngology surgery the same day. Two of them had radiologically
      suspected cervical spine instability. Tracheal intubation was planned with
      careful direct laryngoscopy under manual in-line stabilization of the neck and
      head by an assistant. Direct visualization of the larynx using a Miller blade No.
      2 was impaired in two of the three children in whom the cervical spine was
      immobilized. They were both successfully intubated under endoscopic control using
      the AVIL. CONCLUSION: The AVIL may become a helpful device to aid endotracheal
      intubation in patients when cervical spine immobilization impairs direct
      laryngoscopy.

PMID- 11823400
TI  - Caudal anesthesia reduces the minimum alveolar concentration of enflurane for
      laryngeal mask airway removal in boys.
AB  - PURPOSE: To investigate the effects of caudal analgesia on the minimal alveolar
      concentration of enflurane for laryngeal mask airway (LMA) smooth extubation
      (MACex). METHODS: We studied 50 nonpremedicated children, aged three to ten
      years, ASA physical status I, undergoing surgery for hypospadias repair. After a
      sevoflurane inhalation induction, children were randomized to receive LMA
      insertion with or without ropivacaine caudal analgesia. At the end of surgery, a
      predetermined end-tidal enflurane concentration was achieved, and the LMA was
      removed by an anesthesiologist blinded to group allocation. Each concentration at
      which LMA extubation was attempted was predetermined by the up-and-down method
      (with 0.1% as the step size). When LMA removal was accomplished without coughing,
      clenching teeth or gross purposeful muscular movements during or within one
      minute after removal, it was considered successful. RESULTS: MACex of enflurane
      for LMA removal in the group without caudal anesthesia was 1.04% (95% confidence
      interval, 1.00-1.10) and the LMA MACex of enflurane in the group with caudal
      anesthesia was 0.74% (95% confidence interval, 0.63-0.81). Caudal analgesia
      significantly reduced enflurane requirements by 29% (95% confidence interval, 22
      36%). CONCLUSION: In conclusion, caudal analgesia significantly reduced the LMA
      MACex of enflurane by approximately 29%. Possible mechanisms may be related to
      the analgesic effect of caudal blockade or to the sedative properties of
      neuraxial anesthesia.

PMID- 11823402
TI  - Oral styletted intubation under video control in a patient with a large mobile
      glottic tumour and a difficult airway.
AB  - PURPOSE: With fibreoptic intubation, advancement of the endotracheal tube (ETT)
      through the glottis is blind. Thus, in patients with a laryngeal tumour, there is
      a potential for damage to the tumour. Previously, we proposed the use of a
      fibreoptic bronchoscope (FOB)-video camera system to permit visualization of tube
      passage. We used this technique successfully in a patient with a known difficult
      airway and a large glottic tumour. CLINICAL FEATURES: A 61-yr-old man with a
      known history of difficult laryngoscopic intubation underwent laryngeal
      microsurgery for recurrence of a glottic tumour. As preoperative indirect
      laryngoscopy revealed a large, mobile, and pedunculated glottic lesion
      obstructing the glottic opening, we planned a conventional awake fibreoptic
      intubation. Endoscopy showed that the tumour partially obstructed the glottis and
      the space between the tumour and the glottic opening was very narrow. To avoid
      damage to the tumour, we changed to an alternative fibreoptic intubation
      technique. The FOB attached to a video camera was passed nasally and a jaw thrust
      manoeuver was applied, providing an excellent view of the larynx. An
      anesthesiologist inserted the ETT with a curved stylet orally, and carefully
      advanced the tube tip into the space between the tumour and the glottic opening
      under video control. Absence of damage to the tumour and passage of the tube
      between the cords were confirmed visually. CONCLUSION: This alternative
      intubation technique, providing a view of the tube passage into the glottis, was
      a reasonable method to avoid potential damage to the glottic tumour by blind tube
      passage during conventional fibreoptic intubation.

PMID- 11823403
TI  - Best evidence in anesthetic practice: prevention: recombinant human activated
      protein C reduces mortality in severe sepsis.

PMID- 11823407
TI  - [Anesthesia for urgent abdominal surgery and myasthenia gravis].

PMID- 11823406
TI  - Dobutamine, not dopamine, improves gastric intramucosal pH during resuscitation
      from hemorrhagic shock in dogs.

PMID- 11823408
TI  - Negative pressure pulmonary edema following thyroidectomy.

PMID- 11823409
TI  - Thoracic epidural catheter placement via the caudal approach under
      electrocardiographic guidance.

PMID- 11823410
TI  - Improving styletted oral tracheal intubation: rational use of the OTSU.

PMID- 11823411
TI  - Techniques for rigid stylet use during endotracheal intubation.

PMID- 11823413
TI  - Post-natal knockout of prion protein alters hippocampal CA1 properties, but does
      not result in neurodegeneration.
AB  - Prion protein (PrP) plays a crucial role in prion disease, but its physiological
      function remains unclear. Mice with gene deletions restricted to the coding
      region of PrP have only minor phenotypic deficits, but are resistant to prion
      disease. We generated double transgenic mice using the Cre-loxP system to examine
      the effects of PrP depletion on neuronal survival and function in adult brain.
      Cre-mediated ablation of PrP in neurons occurred after 9 weeks. We found that the
      mice remained healthy without evidence of neurodegeneration or other
      histopathological changes for up to 15 months post-knockout. However, on
      neurophysiological evaluation, they showed significant reduction of
      afterhyperpolarization potentials (AHPs) in hippocampal CA1 cells, suggesting a
      direct role for PrP in the modulation of neuronal excitability. These data
      provide new insights into PrP function. Furthermore, they show that acute
      depletion of PrP does not affect neuronal survival in this model, ruling out loss
      of PrP function as a pathogenic mechanism in prion disease and validating
      therapeutic approaches targeting PrP.

PMID- 11823412
TI  - The connection between transcription and genomic instability.
AB  - Transcription is a central aspect of DNA metabolism that takes place on the same
      substrate as replication, repair and recombination. Not surprisingly, therefore,
      there is a physical and functional connection between these processes. In recent
      years, transcription has proven to be a relevant player in the maintenance of
      genome integrity and in the induction of genetic instability and diversity. The
      aim of this review is to provide an integrative view on how transcription can
      control different aspects of genomic integrity, by exploring different mechanisms
      that might be responsible for transcription-associated mutation (TAM) and
      transcription-associated recombination (TAR).

PMID- 11823414
TI  - Disabled-2 is transcriptionally regulated by ICSBP and augments macrophage
      spreading and adhesion.
AB  - Mice lacking transcription factor interferon consensus sequence binding protein
      (ICSBP) develop a syndrome similar to human chronic myeloid leukemia and are
      immunodeficient. In order to define the molecular mechanisms responsible for the
      cellular defects of ICSBP(-/-) mice, we used bone marrow-derived macrophages
      (BMM) to identify genes deregulated in the absence of ICSBP. Here, we report that
      disabled-2 (Dab2), a signal phosphoprotein, is transcriptionally up-regulated and
      accumulates in the cytoskeleton/membrane fraction of ICSBP(-/-) BMM. Moreover,
      our results revealed Dab2 as a novel IFN-gamma-response gene. Both ICSBP and the
      Ets-transcription factor PU.1 bind to the Dab2 promoter, whereby ICSBP represses
      PU.1-induced Dab2 promoter transactivation in vitro. Notably, repression of Dab2
      expression by ICSBP is also found in myeloid progenitors. Overexpression of Dab2
      leads to accelerated cell adhesion and spreading, accompanied by enhanced actin
      fiber formation. Furthermore, cell adhesion induces transient Dab2
      phosphorylation and its translocation to the cytoskeletal/membrane fraction. Our
      results identify a novel role of Dab2 as an inducer of cell adhesion and
      spreading, and strongly suggest that the up-regulation of Dab2 contributes to the
      hematopoietic defect seen in ICSBP(-/-) mice.

PMID- 11823415
TI  - The ATP synthase is involved in generating mitochondrial cristae morphology.
AB  - The inner membrane of the mitochondrion folds inwards, forming the cristae. This
      folding allows a greater amount of membrane to be packed into the mitochondrion.
      The data in this study demonstrate that subunits e and g of the mitochondrial ATP
      synthase are involved in generating mitochondrial cristae morphology. These two
      subunits are non-essential components of ATP synthase and are required for the
      dimerization and oligomerization of ATP synthase. Mitochondria of yeast cells
      deficient in either subunits e or g were found to have numerous digitations and
      onion-like structures that correspond to an uncontrolled biogenesis and/or
      folding of the inner mitochondrial membrane. The present data show that there is
      a link between dimerization of the mitochondrial ATP synthase and cristae
      morphology. A model is proposed of the assembly of ATP synthase dimers, taking
      into account the oligomerization of the yeast enzyme and earlier data on the
      ultrastructure of mitochondrial cristae, which suggests that the association of
      ATP synthase dimers is involved in the control of the biogenesis of the inner
      mitochondrial membrane.

PMID- 11823416
TI  - The crystal structure of the zymogen catalytic domain of complement protease C1r
      reveals that a disruptive mechanical stress is required to trigger activation of
      the C1 complex.
AB  - C1r is the modular serine protease (SP) that mediates autolytic activation of C1,
      the macromolecular complex that triggers the classical pathway of complement. The
      crystal structure of a mutated, proenzyme form of the catalytic domain of human
      C1r, comprising the first and second complement control protein modules (CCP1,
      CCP2) and the SP domain has been solved and refined to 2.9 A resolution. The
      domain associates as a homodimer with an elongated head-to-tail structure
      featuring a central opening and involving interactions between the CCP1 module of
      one monomer and the SP domain of its counterpart. Consequently, the catalytic
      site of one monomer and the cleavage site of the other are located at opposite
      ends of the dimer. The structure reveals unusual features in the SP domain and
      provides strong support for the hypothesis that C1r activation in C1 is triggered
      by a mechanical stress caused by target recognition that disrupts the CCP1-SP
      interfaces and allows formation of transient states involving important
      conformational changes.

PMID- 11823417
TI  - The dynamin A ring complex: molecular organization and nucleotide-dependent
      conformational changes.
AB  - Here we show that Dictyostelium discoideum dynamin A is a fast GTPase, binds to
      negatively charged lipids, and self-assembles into rings and helices in a
      nucleotide-dependent manner, similar to human dynamin-1. Chemical modification of
      two cysteine residues, positioned in the middle domain and GTPase effector domain
      (GED), leads to altered assembly properties and the stabilization of a highly
      regular ring complex. Single particle analysis of this dynamin A* ring complex
      led to a three-dimensional map, which shows that the nucleotide-free complex
      consists of two layers with 11-fold symmetry. Our results reveal the molecular
      organization of the complex and indicate the importance of the middle domain and
      GED for the assembly of dynamin family proteins. Nucleotide-dependent changes
      observed with the unmodified and modified protein support a mechanochemical
      action of dynamin, in which tightening and stretching of a helix contribute to
      membrane fission.

PMID- 11823418
TI  - Contrasting requirements for ubiquitylation during Fc receptor-mediated
      endocytosis and phagocytosis.
AB  - Fc receptors on leukocytes mediate internalization of antibody-containing
      complexes. Soluble immune complexes are taken up by endocytosis, while large
      antibody-opsonized particles are internalized by phagocytosis. We investigated
      the role of ubiquitylation in internalization of the human FcgammaRIIA receptor
      by endocytosis and phagocytosis. A fusion of FcgammaRIIA to green fluorescent
      protein (GFP) was expressed in ts20 cells, which bear a temperature-sensitive
      mutation in the E1 ubiquitin-activating enzyme. Uptake of soluble IgG complexes
      mediated by FcgammaRIIA-GFP was blocked by incubation at the restrictive
      temperature, indicating that endocytosis requires ubiquitylation. In contrast,
      phagocytosis and phagosomal maturation were largely unaffected when
      ubiquitylation was impaired. FcgammaRIIA-GFP was ubiquitylated in response to
      receptor cross-linking. Elimination of the lysine residues present in the
      cytoplasmic domain of FcgammaRIIA impaired endocytosis, but not phagocytosis. The
      proteasomal inhibitor clasto-lactacystin beta-lactone strongly inhibited
      endocytosis, but did not affect phagocytosis. These studies demonstrate a role
      for ubiquitylation in the endocytosis of immune receptors, and reveal fundamental
      differences in the mechanisms underlying internalization of a single receptor
      depending on the size or multiplicity of the ligand complex.

PMID- 11823419
TI  - The Vtc proteins in vacuole fusion: coupling NSF activity to V(0) trans-complex
      formation.
AB  - The fusion of cellular membranes comprises several steps; membrane attachment
      requires priming of SNAREs and tethering factors by Sec18p/NSF (N-ethylmaleimide
      sensitive factor) and LMA1. This leads to trans-SNARE pairing, i.e. formation of
      SNARE complexes between apposed membranes. The yeast vacuole system has revealed
      two subsequent molecular events: trans-complex formation of V-ATPase proteolipid
      sectors (V(0)) and release of LMA1 from the membrane. We have now identified a
      hetero-oligomeric membrane integral complex of vacuolar transporter chaperone
      (Vtc) proteins integrating these events. The Vtc complex associates with the R
      SNARE Nyv1p and with V(0). Subunits Vtc1p and Vtc4p control the initial steps of
      fusion. They are required for Sec18p/NSF activity in SNARE priming, membrane
      binding of LMA1 and V(0) trans-complex formation. In contrast, subunit Vtc3p is
      required for the latest step, LMA1 release, but dispensible for all preceding
      steps, including V(0) trans-complex formation. This suggests that Vtc3p might act
      close to or at fusion pore opening. We propose that Vtc proteins may couple ATP
      dependent NSF activity to a subset of V(0) sectors in order to activate them for
      V(0) trans-complex formation and/or control fusion pore opening.

PMID- 11823420
TI  - Synaptotagmins form a hierarchy of exocytotic Ca(2+) sensors with distinct Ca(2+)
      affinities.
AB  - Synaptotagmins constitute a large family of membrane proteins implicated in
      Ca(2+)-triggered exocytosis. Structurally similar synaptotagmins are
      differentially localized either to secretory vesicles or to plasma membranes,
      suggesting distinct functions. Using measurements of the Ca(2+) affinities of
      synaptotagmin C2-domains in a complex with phospholipids, we now show that
      different synaptotagmins exhibit distinct Ca(2+) affinities, with plasma membrane
      synaptotagmins binding Ca(2+) with a 5- to 10-fold higher affinity than vesicular
      synaptotagmins. To test whether these differences in Ca(2+) affinities are
      functionally important, we examined the effects of synaptotagmin C2-domains on
      Ca(2+)-triggered exocytosis in permeabilized PC12 cells. A precise correlation
      was observed between the apparent Ca(2+) affinities of synaptotagmins in the
      presence of phospholipids and their action in PC12 cell exocytosis. This was
      extended to PC12 cell exocytosis triggered by Sr(2+), which was also selectively
      affected by high-affinity C2-domains of synaptotagmins. Together, our results
      suggest that Ca(2+) triggering of exocytosis involves tandem Ca(2+) sensors
      provided by distinct plasma membrane and vesicular synaptotagmins. According to
      this hypothesis, plasma membrane synaptotagmins represent high-affinity Ca(2+)
      sensors involved in slow Ca(2+)-dependent exocytosis, whereas vesicular
      synaptotagmins function as low-affinity Ca(2+) sensors specialized for fast
      Ca(2+)-dependent exocytosis.

PMID- 11823421
TI  - Glycogen synthase kinase 3 phosphorylates kinesin light chains and negatively
      regulates kinesin-based motility.
AB  - Membrane-bounded organelles (MBOs) are delivered to different domains in neurons
      by fast axonal transport. The importance of kinesin for fast antero grade
      transport is well established, but mechanisms for regulating kinesin-based
      motility are largely unknown. In this report, we provide biochemical and in vivo
      evidence that kinesin light chains (KLCs) interact with and are in vivo
      substrates for glycogen synthase kinase 3 (GSK3). Active GSK3 inhibited
      anterograde, but not retrograde, transport in squid axoplasm and reduced the
      amount of kinesin bound to MBOs. Kinesin microtubule binding and microtubule
      stimulated ATPase activities were unaffected by GSK3 phosphorylation of KLCs.
      Active GSK3 was also localized preferentially to regions known to be sites of
      membrane delivery. These data suggest that GSK3 can regulate fast anterograde
      axonal transport and targeting of cargos to specific subcellular domains in
      neurons.

PMID- 11823422
TI  - Integrity of intracellular domain of Notch ligand is indispensable for cleavage
      required for release of the Notch2 intracellular domain.
AB  - The biological activity of the soluble form of the Notch ligand (sNL) and
      requirement of the intracellular domain (ICD) of the Notch ligand have been
      debated. Here we show that soluble Delta1 (sD1) activates Notch2 (N2), but much
      more weakly than full-length Delta1 (fD1). Furthermore, tracing the N2 molecule
      after sD1 stimulation revealed that sD1 has a defect in the cleavage releasing
      ICD of N2 (intracellular cleavage), although it triggers cleavage in the
      extracellular domain of N2. This represents the molecular basis of the lower
      activity of sD1 and suggests the presence of an unknown mechanism regulating
      activation of the intracellular cleavage. The fact that Delta1 lacking its ICD
      (D1Delta(ICD)) exhibits the phenotype similar to that exhibited by sD1 indicates
      that the ICD of D1 (D1(ICD)) is involved in such an as yet unknown mechanism.
      Furthermore, the findings that D1Delta(ICD) acts in a dominant-negative fashion
      against fD1 and that the signal-transducing activity of sD1 is enhanced by
      antibody-mediated cross-linking suggest that the multi merization of Delta1
      mediated by D1(ICD) may be required for activation of the N2 intracellular
      cleavage.

PMID- 11823423
TI  - A mutant EGF-receptor defective in ubiquitylation and endocytosis unveils a role
      for Grb2 in negative signaling.
AB  - Ligand-induced desensitization of the epidermal growth factor receptor (EGFR) is
      controlled by c-Cbl, a ubiquitin ligase that binds multiple signaling proteins,
      including the Grb2 adaptor. Consistent with a negative role for c-Cbl, here we
      report that defective Tyr1045 of EGFR, an inducible c-Cbl docking site, enhances
      the mitogenic response to EGF. Signaling potentiation is due to accelerated
      recycling of the mutant receptor and a concomitant defect in ligand-induced
      ubiquitylation and endocytosis of EGFR. Kinetic as well as morphological analyses
      of the internalization-defective mutant receptor imply that c-Cbl-mediated
      ubiquitylation sorts EGFR to endocytosis and to subsequent degradation in
      lysosomes. Unexpectedly, however, the mutant receptor displayed significant
      residual ligand-induced ubiquitylation, especially in the presence of an
      overexpressed c-Cbl. The underlying mechanism seems to involve recruitment of a
      Grb2 c-Cbl complex to Grb2-specific docking sites of EGFR, and concurrent
      acceleration of receptor ubiquitylation and desensitization. Thus, in addition to
      its well-characterized role in mediating positive signals, Grb2 can terminate
      signal transduction by accelerating c-Cbl-dependent sorting of active tyrosine
      kinases to destruction.

PMID- 11823424
TI  - A "three-pronged" binding mechanism for the SAP/SH2D1A SH2 domain: structural
      basis and relevance to the XLP syndrome.
AB  - The SH2 domain protein SAP/SH2D1A, encoded by the X-linked lymphoproliferative
      (XLP) syndrome gene, associates with the hematopoietic cell surface receptor SLAM
      in a phosphorylation-independent manner. By screening a repertoire of synthetic
      peptides, the specificity of SAP/SH2D1A has been mapped and a consensus sequence
      motif for binding identified, T/S-x-x-x-x-V/I, where x represents any amino acid.
      Remarkably, this motif contains neither a Tyr nor a pTyr residue, a hallmark of
      conventional SH2 domain-ligand interactions. The structures of the protein,
      determined by NMR, in complex with two distinct peptides provide direct evidence
      in support of a "three-pronged" binding mechanism for the SAP/SH2D1A SH2 domain
      in contrast to the "two-pronged" binding for conventional SH2 domains.
      Differences in the structures of the two complexes suggest considerable
      flexibility in the SH2 domain, as further confirmed and characterized by hydrogen
      exchange studies. The structures also explain binding defects observed in disease
      causing SAP/SH2D1A mutants and suggest that phosphorylation-independent
      interactions mediated by SAP/SH2D1A likely play an important role in the
      pathogenesis of XLP.

PMID- 11823425
TI  - Cyclin-dependent kinase 5 prevents neuronal apoptosis by negative regulation of c
      Jun N-terminal kinase 3.
AB  - Cyclin-dependent kinase 5 (cdk5) is a serine/threonine kinase activated by
      associating with its neuron-specific activators p35 and p39. Analysis of cdk5(-/
      ) and p35(-/-) mice has demonstrated that both cdk5 and p35 are essential for
      neuronal migration, axon pathfinding and the laminar configuration of the
      cerebral cortex, suggesting that the cdk5-p35 complex may play a role in neuron
      survival. However, the targets of cdk5 that regulate neuron survival are unknown.
      Here, we show that cdk5 directly phosphorylates c-Jun N-terminal kinase 3 (JNK3)
      on Thr131 and inhibits its kinase activity, leading to reduced c-Jun
      phosphorylation. Expression of cdk5 and p35 in HEK293T cells inhibits c-Jun
      phosphorylation induced by UV irradiation. These effects can be restored by
      expression of a catalytically inactive mutant form of cdk5. Moreover, cdk5
      deficient cultured cortical neurons exhibit increased sensitivity to apoptotic
      stimuli, as well as elevated JNK3 activity and c-Jun phosphorylation. Taken
      together, these findings show that cdk5 may exert its role as a key element by
      negatively regulating the c-Jun N-terminal kinase/stress-activated protein kinase
      signaling pathway during neuronal apoptosis.

PMID- 11823426
TI  - NF1/X represses PDGF A-chain transcription by interacting with Sp1 and
      antagonizing Sp1 occupancy of the promoter.
AB  - The regulatory mechanisms mediating basal and inducible platelet-derived growth
      factor (PDGF)-A expression have been the focus of intense recent investigation,
      but repression of PDGF-A expression is largely unexplored. Here we isolated a
      nuclear factor that interacts with the proximal region of the PDGF-A promoter
      using bulk binding assays and chromatography techniques. Peptide mass fingerprint
      and supershift analysis revealed this DNA-binding protein to be NF1/X. NF1/X
      repressed PDGF-A promoter-dependent transcription and endogenous mRNA expression,
      which was reversible by oligonucleotide decoys bearing an NF1/X-binding site.
      Mutation in the DNA-binding domain of NF1/X abolished its repression of PDGF-A
      promoter. NF1/X antagonized the activity of a known activator of the PDGF-A
      chain, Sp1, by inhibiting its occupancy of the proximal PDGF-A promoter. NF1/X
      physically and specifically interacts with Sp1 via its subtype-specific domain
      and blocks Sp1 induction of the promoter. NF1/X residues 311-416 mediated NF1/X
      suppression of basal PDGF-A transcription, whereas residues 243-416 were required
      for NF1/X repression of Sp1-inducible promoter activity. These findings
      demonstrate that repression of PDGF-A gene transcription is governed by interplay
      between NF1/X and Sp1.

PMID- 11823427
TI  - Constitutive and IFN-gamma-induced nuclear import of STAT1 proceed through
      independent pathways.
AB  - STAT1 functions as both a constitutive transcriptional regulator and, in response
      to cytokine stimulation of cells, as an inducible tyrosine-phosphorylated
      transcription factor. Here, we identify and characterize a non-transferable
      nuclear targeting sequence in the STAT1 DNA-binding domain. This conserved signal
      is critical for the interferon-gamma (IFN-gamma)-induced nuclear import of
      phosphorylated STAT1 dimers and requires adjacent positively charged and
      hydrophobic residues for functioning. Additionally, the constitutive
      nucleocytoplasmic shuttling of STAT1 in the absence of IFN-gamma stimulation is
      revealed. Nuclear import and export of unphosphorylated STAT1 are demonstrated to
      be sensitive towards wheat germ agglutinin and to occur independently of the
      import receptor p97. Loss-of-function mutations of the dimer-specific import
      signal block nuclear entry of tyrosine-phosphorylated STAT1, which in turn also
      prevents induction of cytokine-inducible target genes. Nevertheless, nuclear
      import of unphosphorylated STAT1 continues and the STAT1-dependent constitutive
      expression of caspases and the tumor necrosis factor-alpha-mediated induction of
      apoptosis proceed unaltered. Thus, tyrosine-phosphorylated and unphosphorylated
      STAT1 molecules shuttle via independent pathways to distinct sets of target
      genes.

PMID- 11823428
TI  - Identification of a ubiquitin-protein ligase subunit within the CCR4-NOT
      transcription repressor complex.
AB  - The RING finger protein CNOT4 is a component of the CCR4-NOT complex. This
      complex is implicated in repression of RNA polymerase II transcription. Here we
      demonstrate that CNOT4 functions as a ubiquitin-protein ligase (E3). We show that
      the unique C4C4 RING domain of CNOT4 interacts with a subset of ubiquitin
      conjugating enzymes (E2s). Using NMR spectroscopy, we detail the interaction of
      CNOT4 with UbcH5B and characterize RING residues that are critical for this
      interaction. CNOT4 acts as a potent E3 ligase in vitro. Mutations that
      destabilize the E2-E3 interface abolish this activity. Based on these results, we
      present a model of how E3 ligase function within the CCR4-NOT complex relates to
      transcriptional regulation.

PMID- 11823429
TI  - Krox20 and kreisler co-operate in the transcriptional control of segmental
      expression of Hoxb3 in the developing hindbrain.
AB  - In the segmented vertebrate hindbrain, the Hoxa3 and Hoxb3 genes are expressed at
      high relative levels in the rhombomeres (r) 5 and 6, and 5, respectively. The
      single enhancer elements responsible for these activities have been identified
      previously and shown to constitute direct targets of the transcription factor
      kreisler, which is expressed in r5 and r6. Here, we have analysed the
      contribution of the transcription factor Krox20, present in r3 and r5. Genetic
      analyses demonstrated that Krox20 is required for activity of the Hoxb3 r5
      enhancer, but not of the Hoxa3 r5/6 enhancer. Mutational analysis of the Hoxb3 r5
      enhancer, together with ectopic expression experiments, revealed that Krox20
      binds to the enhancer and synergizes with kreisler to promote Hoxb3
      transcription, restricting enhancer activity to their domain of overlap, r5.
      These analyses also suggested contributions from an Ets-related factor and from
      putative factors likely to heterodimerize with kreisler. The integration of
      multiple independent inputs present in overlapping domains by a single enhancer
      is likely to constitute a general mechanism for the patterning of subterritories
      during vertebrate development.

PMID- 11823430
TI  - Importins fulfil a dual function as nuclear import receptors and cytoplasmic
      chaperones for exposed basic domains.
AB  - Many nuclear transport pathways are mediated by importin beta-related transport
      receptors. Here, we identify human importin (Imp) 4b as well as mouse Imp4a,
      Imp9a and Imp9b as novel family members. Imp4a mediates import of the ribosomal
      protein (rp) S3a, while Imp9a and Imp9b import rpS7, rpL18a and apparently
      numerous other substrates. Ribosomal proteins, histones and many other nuclear
      import substrates are very basic proteins that aggregate easily with cytoplasmic
      polyanions such as RNA. Imp9 effectively prevents such precipitation of, for
      example, rpS7 and rpL18a by covering their basic domains. The same applies to
      Imp4, Imp5, Imp7 and Impbeta and their respective basic import substrates. The
      Impbeta-Imp7 heterodimer appears specialized for the most basic proteins, such as
      rpL4, rpL6 and histone H1, and is necessary and sufficient to keep them soluble
      in a cytoplasmic environment prior to rRNA or DNA binding, respectively. Thus,
      just as heat shock proteins function as chaperones for exposed hydrophobic
      patches, importins act as chaperones for exposed basic domains, and we suggest
      that this represents a major and general cellular function of importins.

PMID- 11823431
TI  - Modular self-assembly of a Y-shaped multiprotein complex from seven nucleoporins.
AB  - Now that it is likely that all yeast nucleoporins are known, one of the ultimate
      goals is the in vitro assembly of the entire nuclear pore complex from its
      approximately 30 individual components. Here, we report the reconstitution of
      seven proteins (Nup133p, Nup145p-C, Nup120p, Nup85p, Nup84p, Seh1p and Sec13p)
      into a heptameric 0.5 MDa nuclear pore subcomplex. We found that double plasmid
      transformation combined with bi-cistronic mRNA translation allow the expression
      and assembly of distinct subcomplexes of up to five nucleoporins in a single
      Escherichia coli cell. During the sequential reconstitution of the Nup84p
      complex, smaller assembly intermediates can be isolated, which exhibit modular
      structures determined by electron microscopy that finally make up the whole Y
      shaped Nup84p complex. Importantly, a seventh subunit, Nup133p, was incorporated
      into the complex through its interaction with Nup84p, thereby elongating one arm
      of the Y-shaped assembly to an approximately 40 nm long stalk. Taken together,
      our data document that the Nup84p-Nup133p complex self-assembles in a modular
      concept from distinct smaller nucleoporin construction sets.

PMID- 11823432
TI  - A viral protein inhibits the long range signaling activity of the gene silencing
      signal.
AB  - Post-transcriptional gene silencing (PTGS) provides protection against viruses in
      plants by homology-dependent RNA degradation. PTGS initiated locally produces a
      mobile signal that instructs specific RNA degradation at a distance. Here we show
      that this signal-mediated intercellular spread of PTGS does not occur after PTGS
      initiation in cells expressing cucumber mosaic virus 2b protein (Cmv2b), a
      nucleus-localized plant viral PTGS suppressor. Silencing spread via the signal
      was also effectively blocked in independent assays by expressing Cmv2b only in
      tissues through which the signal must travel to induce PTGS in the target cells.
      Furthermore, the signal imported externally into the Cmv2b-expressing cells was
      not active in triggering degradation of the target RNA and loss of signal
      activity in these cells was associated with a significantly reduced transgene DNA
      methylation. These findings indicate that Cmv2b inhibits the activity of the
      mobile signal and interferes with DNA methylation in the nucleus. Signal
      inactivation provides a mechanistic basis for the known role of Cmv2b in
      facilitating virus spread to tissues outside of the primarily infected sites.

PMID- 11823433
TI  - Transplantation of target site specificity by swapping the endonuclease domains
      of two LINEs.
AB  - Long interspersed elements (LINEs) are ubiquitous genomic elements in higher
      eukaryotes. Here we develop a novel assay to analyze in vivo LINE
      retrotransposition using the telomeric repeat-specific elements SART1 and TRAS1.
      We demonstrate by PCR that silkworm SART1, which is expressed from a recombinant
      baculovirus, transposes in Sf9 cells into the chromosomal (TTAGG)n sequences, at
      the same specific nucleotide position as in the silkworm genome. Thus authentic
      retrotransposition by complete reverse transcription of the entire RNA
      transcription unit and occasional 5' truncation is observed. The
      retrotransposition requires conserved domains in both open reading frames (ORFs),
      including the ORF1 cysteine- histidine motifs. In contrast to human L1,
      recognition of the 3' untranslated region sequence is crucial for SART1
      retrotransposition, which results in efficient trans-complementation. Swapping
      the endonuclease domain from TRAS1 into SART1 converts insertion specificity to
      that of TRAS1. Thus the primary determinant of in vivo target selection is the
      endonuclease domain, suggesting that modified LINEs could be used as gene therapy
      vectors, which deliver only genes of interest but not retrotransposons themselves
      in trans to specific genomic locations.

PMID- 11823434
TI  - Crystal structure of reverse gyrase: insights into the positive supercoiling of
      DNA.
AB  - Reverse gyrase is the only topoisomerase known to positively supercoil DNA. The
      protein appears to be unique to hyperthermophiles, where its activity is believed
      to protect the genome from denaturation. The 120 kDa enzyme is the only member of
      the type I topoisomerase family that requires ATP, which is bound and hydrolysed
      by a helicase-like domain. We have determined the crystal structure of reverse
      gyrase from Archaeoglobus fulgidus in the presence and absence of nucleotide
      cofactor. The structure provides the first view of an intact supercoiling enzyme,
      explains mechanistic differences from other type I topoisomerases and suggests a
      model for how the two domains of the protein cooperate to positively supercoil
      DNA. Coordinates have been deposited in the Protein Data Bank under accession
      codes 1GKU and 1GL9.

PMID- 11823436
TI  - Transvection effects involving DNA methylation during meiosis in the mouse.
AB  - High efficiencies of recombination between LoxP elements were initially recorded
      when the Cre recombinase was expressed in meiotic spermatocytes. However, it was
      unexpectedly found that LoxP recombination fell to very low values at the second
      generation of mice expressing Cre during meiosis. The inability of the LoxP
      elements to serve as recombination substrates was correlated with cytosine
      methylation, initially in LoxP and transgene sequences, but later extending for
      distances of at least several kilobases into chromosomal sequences. It also
      affected the allelic locus, implying a transfer of structural information between
      alleles similar to the transvection phenomenon described in Drosophila. Once
      initiated following Cre-LoxP interaction, neither cis-extension nor transvection
      of the methylated state required the continuous expression of Cre, as they
      occurred both in germinal and somatic cells and in the fraction of the offspring
      that had not inherited the Sycp1-Cre transgene. Therefore, these processes depend
      on a physiological mechanism of establishment and extension of an epigenetic
      state, for which they provide an experimental model.

PMID- 11823435
TI  - Crystal structures of a template-independent DNA polymerase: murine terminal
      deoxynucleotidyltransferase.
AB  - The crystal structure of the catalytic core of murine terminal
      deoxynucleotidyltransferase (TdT) at 2.35 A resolution reveals a typical DNA
      polymerase beta-like fold locked in a closed form. In addition, the structures of
      two different binary complexes, one with an oligonucleotide primer and the other
      with an incoming ddATP-Co(2+) complex, show that the substrates and the two
      divalent ions in the catalytic site are positioned in TdT in a manner similar to
      that described for the human DNA polymerase beta ternary complex, suggesting a
      common two metal ions mechanism of nucleotidyl transfer in these two proteins.
      The inability of TdT to accommodate a template strand can be explained by steric
      hindrance at the catalytic site caused by a long lariat-like loop, which is
      absent in DNA polymerase beta. However, displacement of this discriminating loop
      would be sufficient to unmask a number of evolutionarily conserved residues,
      which could then interact with a template DNA strand. The present structure can
      be used to model the recently discovered human polymerase mu, with which it
      shares 43% sequence identity.

PMID- 11823437
TI  - The DEXD/H-box RNA helicase RHII/Gu is a co-factor for c-Jun-activated
      transcription.
AB  - Tandem affinity purification (TAP) and mass spectrometric peptide sequencing
      showed that the DEAD-box RNA helicase RHII/Gu is a functional interaction partner
      of c-Jun in human cells. The N-terminal transcription activation region of, c-Jun
      interacts with a C-terminal domain of RHII/Gu. This interaction is stimulated by
      anisomycin treatment in a manner that is concurrent with, but independent of, c
      Jun phosphorylation. A possible explanation for this effect is provided by the
      observation that RHII/Gu translocates from nucleolus to nucleoplasm upon
      anisomycin or UV treatment or when JNK signaling is activated by overexpression
      of a constitutively active form of MEKK1 kinase. Several experiments show that
      the RNA helicase activity of RHII/Gu supports c-Jun-mediated target gene
      activation: dominant-negative forms of RHII/Gu, as well as a neutralizing
      antibody against the enzyme, significantly interfered with c-Jun target gene
      activity but not with transcription in general. These findings clarify the
      mechanism of c-Jun-mediated transcriptional regulation, and provide evidence for
      an involvement of RHII/Gu in stress response and in RNA polymerase II-catalyzed
      transcription in mammalian cells.

PMID- 11823438
TI  - Endogenous viral sequences and their potential contribution to heritable virus
      resistance in plants.
AB  - Tobacco endogenous pararetroviruses (TEPRVs) represent the first virus-derived
      repetitive sequence family found in plants. The sequence conservation of TEPRVs
      and the lack of an exogenous form of the virus suggest that TEPRVs serve a
      beneficial function, perhaps by furnishing virus resistance via homologous
      sequence interactions. This hypothesis is supported by the observation that
      TEPRVs are methylated and negligibly transcribed. Moreover, transgenes driven by
      the TEPRV enhancer are silenced and methylated when introduced into tobacco, but
      remain active and unmethylated in non-host species devoid of sequences homologous
      to TEPRVs. In transgenic Arabidopsis, the TEPRV enhancer is active primarily in
      shoot meristems. This suggests that the virus giving rise to TEPRVs could infect
      germ cell precursors, a prerequisite for meiotically heritable insertions into
      host chromosomes. The copy number, organization and methylation of TEPRVs in
      tetraploid tobacco and one of its diploid ancestors, Nicotiana sylvestris, the
      presumed original host for the virus, have remained constant since polyploid
      formation. The remarkable conservation of these features in two independently
      evolving species further supports a role for TEPRVs in viral immunity.

PMID- 11823439
TI  - A cyclophilin functions in pre-mRNA splicing.
AB  - We report that the cyclophilin USA-CyP is part of distinct complexes with two
      spliceosomal proteins and is involved in both steps of pre-mRNA splicing. The
      splicing factors hPrp18 and hPrp4 have a short region of homology that defines a
      high affinity binding site for USA-CyP in each protein. USA-CyP forms separate,
      stable complexes with hPrp18 and hPrp4 in which the active site of the
      cyclophilin is exposed. The cyclophilin inhibitor cyclosporin A slows pre-mRNA
      splicing in vitro, and we show that its inhibition of the second step of splicing
      is caused by blocking the action of USA-CyP within its complex with hPrp18.
      Cyclosporin A also slows splicing in vivo, and we show that this slowing results
      specifically from inhibition of USA-CyP. Our results lead to a model in which USA
      CyP is carried into the spliceosome in complexes with hPrp4 and hPrp18, and USA
      CyP acts during splicing within these complexes. These results provide an example
      of the function of a cyclophilin in a complex process and provide insight into
      the mechanisms of action of cyclophilins.

PMID- 11823440
TI  - Direct measurement of the male recombination fraction in the human beta-globin
      hot spot.
AB  - Recombination was measured across nine intervals in the human beta-globin gene
      cluster by single-sperm analysis. A recombination fraction of approximately 0.9%
      was calculated across an approximately 11 kb region using a new method to
      estimate recombination fractions from single-sperm typing data. No recombination
      was detected in an adjacent approximately 90 kb region that extends upstream of
      the beta-globin cluster. These data are consistent with previous estimates based
      on population genetic analysis, and suggest a recombination rate of nearly two
      orders of magnitude greater than the genome average of approximately 1 cM/Mb.
      Because recombination hot spots will destroy linkage disequilibrium across small
      physical regions, knowledge about the location and strength of such hot spots
      could be extremely valuable for genetic association studies.

PMID- 11823441
TI  - Assembly and iron-binding properties of human frataxin, the protein deficient in
      Friedreich ataxia.
AB  - Friedreich ataxia (FRDA) is an autosomal recessive degenerative disease caused by
      a deficiency of frataxin, a conserved mitochondrial protein of unknown function.
      Mitochondrial iron accumulation, loss of iron-sulfur cluster-containing enzymes
      and increased oxidative damage occur in yeast and mouse frataxin-depleted mutants
      as well as tissues and cell lines from FRDA patients, suggesting that frataxin
      may be involved in export of iron from the mitochondria, synthesis of iron-sulfur
      clusters and/or protection from oxidative damage. We have previously shown that
      yeast frataxin has structural and functional features of an iron storage protein.
      In this study we have investigated the function of human frataxin in Escherichia
      coli and Saccharomyces cerevisiae. When expressed in E.coli, the mature form of
      human frataxin assembles into a stable homopolymer that can bind approximately 10
      atoms of iron per molecule of frataxin. The iron-loaded homopolymer can be
      detected on non-denaturing gels by either protein or iron staining demonstrating
      a stable association between frataxin and iron. As analyzed by gel filtration and
      electron microscopy, the homopolymer consists of globular particles of
      approximately 1 MDa and ordered rod-shaped polymers of these particles that
      accumulate small electron-dense cores. When the human frataxin precursor is
      expressed in S.cerevisiae, the mitochondrially generated mature form is separated
      by gel filtration into monomer and a high molecular weight pool of >600 kDa. A
      high molecular weight pool of frataxin is also present in mouse heart indicating
      that frataxin can assemble under native conditions. In radiolabeled yeast cells,
      human frataxin is recovered by immunoprecipitation with approximately five atoms
      of (55)Fe bound per molecule. These findings suggest that FRDA results from
      decreased mitochondrial iron storage due to frataxin deficiency which may impair
      iron metabolism, promote oxidative damage and lead to progressive iron
      accumulation.

PMID- 11823442
TI  - Modifier effect of ENOS in autosomal dominant polycystic kidney disease.
AB  - A significant phenotypical variability is observed in autosomal dominant
      polycystic kidney disease (ADPKD). ADPKD is associated with altered endothelial
      dependent vasodilation and decreased vascular production of nitric oxide (NO).
      Thus, ENOS, the gene coding for the endothelial nitric oxide synthase (eNOS),
      could have a modifier effect in ADPKD. In order to test this hypothesis, we
      genotyped 173 unrelated ADPKD patients from Belgium and the north of France for
      the Glu298Asp, intron 4 VNTR and T-786C polymorphisms of ENOS and looked for
      their influence on the age at end-stage renal disease (ESRD). In males (n = 93),
      the Glu298Asp polymorphism was associated with a lower age at ESRD (Glu/Asp +
      Asp/Asp: 49.0 +/- 1.2 years, n = 53; Glu/Glu: 53.5 +/- 1.5 years, n = 40; simple
      regression, P = 0.02; multiple regression, P = 0.006). This effect was confirmed
      in a subset of males linked to PKD1 and reaching ESRD before age 45, and by a
      cumulative renal survival analysis in PKD1-linked families. Further studies
      demonstrated that NO synthase (NOS) activity was decreased in renal artery
      samples from ADPKD males harbouring the Asp298 allele, in association with post
      translational modifications and partial cleavage of eNOS. No significant effect
      of the other polymorphisms was found in males, and no polymorphism influenced the
      age at ESRD in females. In conclusion, the frequent Glu298Asp polymorphism of
      ENOS is associated with a 5 year lower mean age at ESRD in this subset of ADPKD
      males. This effect could be due to a decreased NOS activity and a partial
      cleavage of eNOS, leading to a further decrease in the vascular production of NO.

PMID- 11823443
TI  - The severe G480C cystic fibrosis mutation, when replicated in the mouse,
      demonstrates mistrafficking, normal survival and organ-specific bioelectrics.
AB  - The majority of cystic fibrosis patients produce a mutant form of CFTR
      (DeltaF508) which has been shown to be mislocalized in both humans and mice.
      G480C, another clinically 'severe' mutation, has also been demonstrated to be
      defective in its intracellular processing, but when allowed to traffic in Xenopus
      oocytes showed similar channel characteristics to that of wild-type CFTR. We have
      replicated the G480C mutation in the murine Cftr gene using the 'hit and run'
      double recombination procedure. As expected, the G480C cystic fibrosis mouse
      model expresses the G480C mutant transcript at a level comparable to that of wild
      type CFTR: The homozygous mutant mice were fertile, had normal survival, weight,
      tooth colour and no evidence of caecal blockage, despite mild goblet cell
      hypertrophy in the intestine. Analysis of the mutant protein revealed that the
      majority of G480C CFTR was abnormally processed and no G480C CFTR-specific
      immunostaining in the apical membranes of intestinal cells was detected. The
      bioelectric phenotype of these mice revealed organ-specific electrophysiological
      effects. In contrast to DeltaF508 'hit and run' homozygotes, the classic defect
      of forskolin-induced chloride ion transport is not replicated in the caecum, but
      the response to low chloride in the nose is clearly defective in the G480C mutant
      animals. The mild phenotype of these G480C mutant animals combined with the
      defective chloride transport in the nose uniquely provides a valuable resource to
      test novel pharmacological agents aimed at improving trafficking and correcting
      the electrophysiological defect in the respiratory tract.

PMID- 11823444
TI  - Neurodevelopmental defects resulting from ATRX overexpression in transgenic mice.
AB  - Several X-linked mental retardation syndromes are caused by mutations in the ATRX
      gene. Common clinical features associated with ATRX mutations include severe
      mental retardation, characteristic facial anomalies and variable degrees of
      urogenital defects and alpha-thalassemia. Although the ATRX protein is a member
      of the SWI/SNF family of chromatin remodeling proteins, little is known about the
      biochemical activity of the ATRX protein or its in vivo function during
      development. Here we demonstrate that ATRX is part of a large multiprotein
      complex similar in size to the SWI/SNF complex. Furthermore, we have generated
      transgenic mice that overexpress ATRX as an initial model for studying the
      function of this protein during development. Misexpression of ATRX was associated
      with growth retardation, neural tube defects and a high incidence of embryonic
      death. Moreover, brains from E10.5 transgenic embryos displayed abnormal growth
      and organization of the ventricular zone that was highly convoluted in the most
      severely affected embryos. Transgenic mice that survived to birth exhibited a
      high incidence of perinatal death, as well as seizures, mild craniofacial
      anomalies and abnormal behavior. Our findings indicate that ATRX dosage is
      crucial for normal development and organization of the cortex, and emphasize the
      relevance of our model for the study of ATRX function and disease pathogenesis.

PMID- 11823445
TI  - A chronic inflammatory response dominates the skeletal muscle molecular signature
      in dystrophin-deficient mdx mice.
AB  - Mutations in dystrophin cause Duchenne muscular dystrophy (DMD), but absent
      dystrophin does not invariably cause necrosis in all muscles, life stages and
      species. Using DNA microarray, we established a molecular signature of
      dystrophinopathy in the mdx mouse, with evidence that secondary mechanisms are
      key contributors to pathogenesis. We used variability controls, adequate
      replicates and stringent analytic tools, including significance analysis of
      microarrays to estimate and manage false positive rates. In leg muscle, we
      identified 242 differentially expressed genes, >75% of which have not been
      previously reported as altered in human or animal dystrophies. Data provide
      evidence for coordinated activity of numerous components of a chronic
      inflammatory response, including cytokine and chemokine signaling, leukocyte
      adhesion and diapedesis, invasive cell type-specific markers, and complement
      system activation. Selective chemokine upregulation was confirmed by RT-PCR and
      immunoblot, and may be a key determinant of the nature of the inflammatory
      response in dystrophic muscle. Up-regulation of secreted phosphoprotein 1
      (minopontin, osteopontin) mRNA and protein in dystrophic muscle identified a
      novel linkage between inflammatory cells and repair processes. Extracellular
      matrix genes were up-regulated in mdx to levels similar to those in DMD. Since,
      unlike DMD, mdx exhibits little fibrosis, data suggest that collagen regulation
      at post-transcriptional stages mediates extensive fibrosis in DMD. Taken
      together, these data identify a relatively neglected aspect of DMD, suggest new
      treatment avenues, and highlight the value of genome-wide profiling in study of
      complex disease processes.

PMID- 11823446
TI  - Reduced fertility and hypersensitivity to mitomycin C characterize Fancg/Xrcc9
      null mice.
AB  - Fanconi anemia (FA) is a heterogeneous autosomal recessive chromosomal
      instability syndrome associated with diverse developmental abnormalities,
      progressive bone marrow failure and a predisposition to cancer. Spontaneous
      chromosomal breakage and hypersensitivity to DNA cross-linking agents
      characterize the cellular FA phenotype. The gene affected in FA complementation
      group G patients was initially identified as XRCC9, for its ability to partially
      correct the cellular phenotype of the Chinese hamster ovary (CHO) cell mutant
      UV40. By targeted disruption we generated Fancg/Xrcc9 null mice. Fancg knock-out
      (KO) mice were born at expected Mendelian frequencies and showed normal
      viability. In mice, functional loss of Fancg did not result in developmental
      abnormalities or a pronounced incidence of malignancies. During a 1 year follow
      up, blood cell parameters of Fancg KO mice remained within normal values,
      revealing no signs of anemia. Male and female mice deficient in Fancg showed
      hypogonadism and impaired fertility, consistent with the phenotype of FA
      patients. Mouse embryonic fibroblasts (MEFs) from the KO animals exhibited the FA
      characteristic cellular response in showing enhanced spontaneous chromosomal
      instability and a hyper-responsiveness to the clastogenic and antiproliferative
      effects of the cross-linking agent mitomycin C (MMC). The sensitivity to UV, X
      rays and methyl methanesulfonate, reported for the CHO mutant cell line UV40, was
      not observed in Fancg(-/-) MEFs. Despite a lack of hematopoietic failure in the
      KO mice, clonogenic survival of bone marrow cells in vitro was strongly reduced
      in the presence of MMC. The characteristics of the Fancg(-/-) mice closely
      resemble those reported for Fancc and Fanca null mice, supporting a tight
      interdependence of the corresponding gene products in a common pathway.

PMID- 11823447
TI  - Folic acid prevents exencephaly in Cited2 deficient mice.
AB  - Cited2 (also Mrg1/p35srj) is a member of a new conserved gene family that is
      expressed during mouse development and in adult tissues. In order to investigate
      the function of Cited2 during mouse embryogenesis, we introduced a null mutation
      into the Cited2 locus. Cited2(-/-) mutants died at late gestation and exhibited
      heart defects and exencephaly, arising from defective closure of the midbrain
      (MB) and hindbrain. Initiation of neural tube closure at the forebrain-midbrain
      (FB-MB) boundary, an essential step for closure of the cranial neural tube, was
      impaired in the Cited2(-/-) mutants. Gene marker analysis using in situ
      hybridization revealed that the patterning of the anterior neural plate and head
      mesenchyme was little affected or normal in the Cited2(-/-) embryos. However,
      Cited2 was required for the survival of neuroepithelial cells and its absence led
      to massive apoptosis in dorsal neuroectoderm around the FB-MB boundary and in a
      restricted transverse domain in the hindbrain. Treatment with folic acid
      significantly reduced the exencephalic phenotype in the Cited2(-/-) embryos both
      in vivo and in vitro. However, assessment of folate metabolism revealed no defect
      in the Cited2(-/-) mutants, and the elevated apoptosis observed in the
      neuroepithelium of the Cited2(-/-) mutants was apparently not decreased by folic
      acid supplementation. To our knowledge, the Cited2 mouse represents the first
      genetic model in which folic acid can prevent a defect in neural tube closure by
      a mechanism other than the neutralization of a defect in folate homeostasis.

PMID- 11823448
TI  - Linkage analysis conditional on HLA status in a large North American pedigree
      supports the presence of a multiple sclerosis susceptibility locus on chromosome
      12p12.
AB  - Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the
      central nervous system with a probable immune-mediated pathogenesis. Strong
      evidence supports the hypothesis that MS is determined by genetic and
      environmental factors, but these factors remain largely undefined. The genetic
      component is suggested by a higher concordance rate in monozygotic (28%) versus
      dizygotic (5%) twins as well as familial recurrence risk. Several studies have
      shown association of MS with the histocompatibility leukocyte antigen (HLA) class
      II region, specifically DR15, DQ6. However, there is no convincing evidence of a
      common susceptibility locus. We have identified a pedigree of Pennsylvania Dutch
      extraction, in which MS segregates with an autosomal dominant inheritance
      pattern. We have collected blood samples from 18 family members, seven of whom
      show typical signs of MS lesions by magnetic resonance imaging. The 18
      individuals were serotyped for HLA class I and II and analyzed by a genome-wide
      screen for linkage analysis. We have found evidence for suggestive linkage to
      markers on 12p12 with a maximum multipoint LOD score of 2.71, conditional on the
      presence of DR15, DQ6. Contingency table analysis showed that all MS affected
      individuals have both the DR15, DQ6 allele and the 12p12 haplotype whereas the
      unaffected individuals have either one or neither of these markers (P = 0.00011).
      Our data suggests that both HLA DR15, DQ6 and a novel locus on chromosome 12p12
      may be necessary for development of MS in this family.

PMID- 11823450
TI  - The relationship between somatic mtDNA rearrangements, human heart disease and
      aging.
AB  - The lifetime accumulation of low-abundance, somatic mtDNA re-arrangements
      (sublimons) has been proposed as a potential contributor to aging, and also to
      diseases such as cardiomyopathy or coronary heart disease. Tissue-specific
      sublimons, varying in abundance by three orders of magnitude between individuals,
      have recently been observed in myocardium of control subjects. To study the
      relationship between myocardial sublimon levels and various types of cardiac
      disease and aging, we applied a semi-quantitative fluorescent PCR assay on
      cellular DNA extracted from left ventricle in a series of 300 well characterized
      male victims of sudden death up to age 70 (Helsinki Sudden Death Study). The most
      prevalent classes of sublimons were present at <0.1 to 91 copies per cell, but
      their abundance did not correlate with any cardiac disease phenotype. In multiple
      regression analyses age (beta = 0.43, P < 0.0001) and smoking (bet = 0.25, P =
      0.012) were the only independent factors found to correlate with sublimon levels.
      Thus, sublimons are inferred to accumulate with age in myocardium of a subset of
      individuals, but to levels where they do not appear to have any phenotypic
      effects during a typical life span. We propose that, instead of being a causal
      factor in cardiac aging, sublimons co-exist with wild-type mtDNA in an
      equilibrium which is regulated by as yet unknown mechanisms.

PMID- 11823449
TI  - Synthesis, purification and structural and functional characterization of
      recombinant form of a common genetic variant of human luteinizing hormone.
AB  - A common genetic variant (V) of luteinizing hormone (LH), with two mutations
      (Trp(8)Arg and Ile(15)Thr) and an extra glycosylation consensus site (Asn(13)-Ala
      Thr), is associated with abnormalities of reproductive function. To address the
      molecular basis of the functional differences between V- and wild-type (WT)-LH,
      recombinant (rec) forms of WT- and V-LH were synthesized in human embryonic
      kidney (HEK 293) cells. The rec hormones synthesized were rigorously purified
      employing affinity, immunoaffinity and ion exchange chromatographies (final
      purity approximately 12 000 IU/mg, 180-fold purification, 28% recovery).
      Functional properties of the hormone preparations were compared in vitro and in
      vivo. The molecular size of both rec LHs was 31 kDa, as determined by SDS-PAGE.
      Although the mutations in V-LHbeta did not significantly affect the affinity of
      LH receptor (LHR) binding (Kd approximately 0.4 nmol/L), V-LH had higher in vitro
      biopotency than WT-LH, in terms of mLTC-1 mouse Leydig tumor cell cAMP and
      progesterone (P) production, and steroidogenic acute regulatory protein (StAR)
      expression. In addition, in HEK 293 cells expressing the human LHR, V-LH
      demonstrated 1.8-fold higher response of inositol trisphosphate (IP(3))
      production than WT-LH. Furthermore, HEK 293 cells expressing the ElK1 trans
      reporting plasmids displayed 2.7-fold greater luciferase response to V-LH than WT
      LH, documenting stimulation of the mitogen-activated protein kinase (MAPK)
      pathway. The in vivo half-life of V-LH was clearly faster (5-9 min) than that of
      WT-LH (12-22 min) and human chorionic gonadotropin (hCG; 50-70 min), when
      injected into rat circulation. It is worth noting that analysis by matrix
      assisted laser desorption ionization-mass spectrometry (MALDI-MS) demonstrated
      clear differences in structures of carbohydrate side chains attached to the two
      forms of rec LHs, including incomplete processing of high mannose glycans
      (Man(5,8,9)) in V-LH, suggesting different pathways in its intracellular
      trafficking. Collectively, the present findings provide the molecular basis for
      the qualitative and quantitative differences in LH action that are observed in
      carriers of the V-LHbeta allele.

PMID- 11823451
TI  - Functional characterization of mutations in the GDNF gene of patients with
      Hirschsprung disease.
AB  - Hirschsprung disease (HSCR) is a congenital disorder characterized by the absence
      of enteric nervous plexuses in hind gut. Ten to forty percent of HSCR patients
      carry a dominant loss-of-function mutation in the gene encoding the receptor
      tyrosine kinase RET, a receptor for glial cell line-derived neurotrophic factor
      (GDNF). Although several mutations have also been found in the GDNF gene of HSCR
      patients, their impact on GDNF function is unknown. In this study, we have
      characterized the effect of these mutations on the ability of GDNF to bind and
      activate its receptors. Although none of the four mutations analyzed appeared to
      affect the ability of GDNF to activate RET, two of them resulted in a significant
      reduction in the binding affinity of GDNF for the binding subunit of the receptor
      complex, GFR(alpha)1. Our results indicate that, although none of the GDNF
      mutations identified so far in HSCR patients are per se likely to result in HSCR,
      two of these mutations (i.e. D150N and I211M) may, in conjunction with other
      genetic lesions, contribute to the pathogenesis of this disease.

PMID- 11823452
TI  - The human intronless melanocortin 4-receptor gene is NMD insensitive.
AB  - Nonsense-mediated decay (NMD) is a phylogenetically widely conserved mechanism
      that contributes to the fidelity of gene expression. NMD inhibits the
      accumulation of nonsense- or frameshift-mutated mRNA and thus minimizes the
      synthesis of truncated proteins with potential dominant negative effects. Yeast
      and higher eukaryotes use somewhat diverse mechanisms to promote NMD and to
      discriminate between premature and physiological translation termination codons.
      NMD in yeast involves the binding of specific RNA-binding proteins to cis-acting
      exonic elements. In contrast, NMD of the intron-containing genes of higher
      eukaryotes is splicing-dependent. Here, we investigated the NMD sensitivity of
      nonsense-mutated transcripts of the naturally intronless human melanocortin 4
      receptor (MC4-R) gene. Nonsense-mutated variants of MC4-R transcripts are stable
      and express truncated proteins that are detectable in the lysates of transfected
      cells. Thus, the naturally intronless MC4-R gene and probably many other
      intronless genes fail to be monitored by the NMD pathway.

PMID- 11823453
TI  - Genetic and biophysical basis of sudden unexplained nocturnal death syndrome
      (SUNDS), a disease allelic to Brugada syndrome.
AB  - Sudden unexplained nocturnal death syndrome (SUNDS), a disorder found in
      southeast Asia, is characterized by an abnormal electrocardiogram with ST-segment
      elevation in leads V1-V3 and sudden death due to ventricular fibrillation,
      identical to that seen in Brugada syndrome. We screened patients with SUNDS for
      mutations in SCN5A, the gene known to cause Brugada syndrome, as well as genes
      encoding ion channels associated with the long-QT syndrome. Ten families were
      enrolled, and screened for mutations using single-strand DNA conformation
      polymorphism analysis, denaturing high-performance liquid chromatography and DNA
      sequencing. Mutations were identified in SCN5A in three families. One mutation,
      R367H, lies in the first P segment of the pore-lining region between the DIS5 and
      DIS6 transmembrane segments of SCN5A. A second mutation, A735V, lies in the first
      transmembrane segment of domain II (DIIS1) close to the first extracellular loop
      between DIIS1 and DIIS2, whereas the third mutation, R1192Q, lies in domain III.
      Analysis of these mutations in Xenopus oocytes showed that the R367H mutant
      channel did not express any current and the likely effect of this mutation is to
      depress peak current due to the loss of one functional allele. The A735V mutant
      expressed currents with steady state activation voltage shifted to more positive
      potentials. The R1192Q mutation accelerated the inactivation of the sodium
      channel current. Both mutations resulted in reduced sodium channel current
      (I(Na)) at a time corresponding to the end of phase 1 of the action potential, as
      described previously in the Brugada syndrome. Based upon these observations we
      suggest that SUNDS and Brugada syndrome are phenotypically, genetically and
      functionally the same disorder.

PMID- 11823454
TI  - Distinct binding sites in the structure of alpha 2-macroglobulin mediate the
      interaction with beta-amyloid peptide and growth factors.
AB  - Alpha(2)-macroglobulin (alpha(2)M) and its receptor, low density lipoprotein
      receptor-related protein (LRP), function together to facilitate the cellular
      uptake and degradation of beta-amyloid peptide (Abeta). In this study, we
      demonstrate that Abeta binds selectively to alpha(2)M that has been induced to
      undergo conformational change by reaction with methylamine. Denatured alpha(2)M
      subunits, which were immobilized on polyvinylidene difluoride membranes, bound
      Abeta, suggesting that alpha(2)M tertiary and quaternary structure are not
      necessary. To determine whether a specific sequence in alpha(2)M is responsible
      for Abeta binding, we prepared and analyzed defined alpha(2)M fragments and
      glutathione S-transferase-alpha(2)M peptide fusion proteins. A single sequence,
      centered at amino acids (aa) 1314-1365, was identified as the only major Abeta
      binding site. Importantly, Abeta did not bind to the previously characterized
      growth factor-binding site (aa 718-734). Although the Abeta binding sequence is
      adjacent to the binding site for LRP, the results of experiments with mutated
      fusion proteins indicate that the two sites are distinct. Furthermore, a
      saturating concentration of Abeta did not inhibit LRP-mediated clearance of
      alpha(2)M-MA in mice. Using various methods, we determined that the K(D) for the
      interaction of Abeta with its binding site in the individual alpha(2)M subunit is
      0.7-2.4 microm. The capacity of alpha(2)M to bind Abeta and deliver it to LRP may
      be greater than that predicted by the K(D), because each alpha(2)M subunit may
      bind Abeta and the bound Abeta may multimerize. These studies suggest a model in
      which alpha(2)M has three protein interaction sites with distinct specificities,
      mediating the interaction with Abeta, growth factors, and LRP.

PMID- 11823455
TI  - Cloning and mutational analysis of the gamma gene from Azotobacter vinelandii
      defines a new family of proteins capable of metallocluster binding and protein
      stabilization.
AB  - Dinitrogenase is a heterotetrameric (alpha(2)beta(2)) enzyme that catalyzes the
      reduction of dinitrogen to ammonium and contains the iron-molybdenum cofactor
      (FeMo-co) at its active site. Certain Azotobacter vinelandii mutant strains
      unable to synthesize FeMo-co accumulate an apo form of dinitrogenase (lacking
      FeMo-co), with a subunit composition alpha(2)beta(2)gamma(2), which can be
      activated in vitro by the addition of FeMo-co. The gamma protein is able to bind
      FeMo-co or apodinitrogenase independently, leading to the suggestion that it
      facilitates FeMo-co insertion into the apoenzyme. In this work, the non-nif gene
      encoding the gamma subunit (nafY) has been cloned, sequenced, and found to encode
      a NifY-like protein. This finding, together with a wealth of knowledge on the
      biochemistry of proteins involved in FeMo-co and FeV-co biosyntheses, allows us
      to define a new family of iron and molybdenum (or vanadium) cluster-binding
      proteins that includes NifY, NifX, VnfX, and now gamma. In vitro FeMo-co
      insertion experiments presented in this work demonstrate that gamma stabilizes
      apodinitrogenase in the conformation required to be fully activable by the
      cofactor. Supporting this conclusion, we show that strains containing mutations
      in both nafY and nifX are severely affected in diazotrophic growth and
      extractable dinitrogenase activity when cultured under conditions that are likely
      to occur in natural environments. This finding reveals the physiological
      importance of the apodinitrogenase-stabilizing role of which both proteins are
      capable. The relationship between the metal cluster binding capabilities of this
      new family of proteins and the ability of some of them to stabilize an apoenzyme
      is still an open matter.

PMID- 11823456
TI  - Identification of novel point mutations in ERK2 that selectively disrupt binding
      to MEK1.
AB  - Extracellular signal-regulated kinases 1 and 2 (ERK1 and ERK2) are essential
      components of pathways through which signals received at membrane receptors are
      converted into specific changes in protein function and gene expression. As with
      other members of the mitogen-activated protein (MAP) kinase family, ERK1 and ERK2
      are activated by phosphorylations catalyzed by dual-specificity protein kinases
      known as MAP/ERK kinases (MEKs). MEKs exhibit stringent specificity for
      individual MAP kinases. Indeed, MEK1 and MEK2 are the only known activators of
      ERK1 and ERK2. ERK2 small middle dotMEK1/2 complexes can be detected in vitro and
      in vivo. The biochemical nature of such complexes and their role in MAP kinase
      signaling are under investigation. This report describes the use of a yeast two
      hybrid screen to identify point mutations in ERK2 that impair its interaction
      with MEK1/2, yet do not alter its interactions with other proteins. ERK2 residues
      identified in this screen are on the surface of the C-terminal domain of the
      kinase, either within or immediately preceding alpha-helix G, or within the MAP
      kinase insert. Some mutations identified in this manner impaired the two-hybrid
      interaction of ERK2 with both MEK1 and MEK2, whereas others had a predominant
      effect on the interaction with either MEK1 or MEK2. Mutant ERK2 proteins
      displayed reduced activation in HEK293 cells following epidermal growth factor
      treatment, consistent with their impaired interaction with MEK1/2. However, ERK2
      proteins containing MEK-specific mutations retained kinase activity, and were
      similar to wild type ERK2 in their activation following overexpression of
      constitutively active MEK1. Unlike wild type ERK2, proteins containing MEK
      specific point mutations were constitutively localized in the nucleus, even in
      the presence of overexpressed MEK1. These data suggest an essential role for the
      MAP kinase insert and residues within or just preceding alpha-helix G in the
      interaction of ERK2 with MEK1/2.

PMID- 11823457
TI  - Oxalate selectively activates p38 mitogen-activated protein kinase and c-Jun N
      terminal kinase signal transduction pathways in renal epithelial cells.
AB  - Oxalate, a metabolic end product, is an important factor in the pathogenesis of
      renal stone disease. Oxalate exposure to renal epithelial cells results in re
      initiation of the DNA synthesis, altered gene expression, and apoptosis, but the
      signaling pathways involved in these diverse effects have not been evaluated. The
      effects of oxalate on mitogen- and stress-activated protein kinase signaling
      pathways were studied in LLC-PK1 cells. Exposure to oxalate (1 mM) rapidly
      stimulated robust phosphorylation and activation of p38 MAPK. Oxalate exposure
      also induced modest activation of JNK, as monitored by phosphorylation of c-Jun.
      In contrast, oxalate exposure had no effect on phosphorylation and enzyme
      activity of p42/44 MAPK. We also show that specific inhibition of p38 MAPK by 4(4
      (fluorophenyl)-2-(4-methylsulfonylphenyl)-5-(4-pyridyl)imidazole (SB203580) or by
      overexpression of a kinase-dead dominant negative mutant of p38 MAPK abolishes
      oxalate induced re-initiation of DNA synthesis in LLC-PK1 cells. The inhibition
      is dose-dependent and correlates with in situ activity of native p38 MAP kinase,
      determined as MAPK-activated protein kinase-2 activity in cell extracts. Thus,
      this study not only provides the first demonstration of selective activation of
      p38 MAPK and JNK signaling pathways by oxalate but also suggests that p38 MAPK
      activity is essential for the effects of oxalate on re-initiation of DNA
      synthesis.

PMID- 11823458
TI  - Estrogen lowers Alzheimer beta-amyloid generation by stimulating trans-Golgi
      network vesicle biogenesis.
AB  - Estrogen reduces the risk of Alzheimer's disease in post-menopausal women, beta
      amyloid (Abeta) burden in animal models of Alzheimer's disease, and secretion of
      Abeta from neuronal cultures. The biological basis for these effects remains
      unknown. Here, utilizing cell-free systems derived from both neuroblastoma cells
      and primary neurons, we demonstrate that 17beta-estradiol (17beta-E2) stimulates
      formation of vesicles containing the beta-amyloid precursor protein (betaAPP)
      from the trans-Golgi network (TGN). Accelerated betaAPP trafficking precludes
      maximal Abeta generation within the TGN. 17beta-E2 appears to modulate TGN
      phospholipid levels, particularly those of phosphatidylinositol, and to recruit
      soluble trafficking factors, such as Rab11, to the TGN. Together, these results
      suggest that estrogen may exert its anti-Abeta effects by regulating betaAPP
      trafficking within the late secretory pathway. These results suggest a novel
      mechanism through which 17beta-E2 may act in estrogen-responsive tissues and
      illustrate how altering the kinetics of the transport of a protein can influence
      its metabolic fate.

PMID- 11823459
TI  - The antituberculosis drug ethionamide is activated by a flavoprotein
      monooxygenase.
AB  - Ethionamide (ETA), a prodrug that must undergo metabolic activation to exert its
      cytotoxic effects, is a second line drug against tuberculosis, a disease that
      infects more than a third of the world's population. It has been proposed, on the
      basis of genetic experiments, that ETA is activated in Mycobacterium tuberculosis
      by the protein encoded by the gene Rv3854c (DeBarber, A. E., Mdluli, K., Bosman,
      M., Bekker, L.-G., and Barry, C. E., III (2000) Proc. Natl. Acad. Sci. U. S. A.
      97, 9677-9682; Baulard, A. R., Betts, J. C., Engohang-Ndong, J., Quan, S.,
      McAdam, R. A., Brennan, P. J., Locht, C., and Besra, G. S. (2000) J. Biol. Chem.
      275, 28326-28331). We report here the expression, purification, and
      characterization of the protein encoded by this gene. Our results establish that
      the enzyme (EtaA) is an FAD-containing enzyme that oxidizes ETA to the
      corresponding S-oxide. The S-oxide, which has a similar biological activity as
      ETA, is further oxidized by EtaA to 2-ethyl-4-amidopyridine, presumably via the
      unstable doubly oxidized sulfinic acid intermediate. This flavoenzyme also
      oxidizes thiacetazone, thiobenzamide, and isothionicotinamide and thus is
      probably responsible, as suggested by the observation of crossover resistance,
      for the oxidative activation of other thioamide antitubercular drugs.

PMID- 11823460
TI  - A Chinese cabbage cDNA with high sequence identity to phospholipid hydroperoxide
      glutathione peroxidases encodes a novel isoform of thioredoxin-dependent
      peroxidase.
AB  - A cDNA, PHCC-TPx, specifying a protein highly homologous to known phospholipid
      hydroperoxide glutathione peroxidases was isolated from a Chinese cabbage cDNA
      library. PHCC-TPx encodes a preprotein of 232 amino acids containing a putative N
      terminal chloroplast targeting sequence and three conserved Cys residues
      (Cys(107), Cys(136), and Cys(155)). The mature form of enzyme without the signal
      peptide was expressed in Escherichia coli, and the recombinant protein was found
      to utilize thioredoxin (Trx) but not GSH as an electron donor. In the presence of
      a Trx system, the protein efficiently reduces H(2)O(2) and organic
      hydroperoxides. Complementation analysis shows that overexpression of the PHCC
      TPx restores resistance to oxidative stress in yeast mutants lacking GSH but
      fails to complement mutant lacking Trx, suggesting that the reducing agent of
      PHCC-TPx in vivo is not GSH but is Trx. Mutational analysis of the three Cys
      residues individually replaced with Ser shows that Cys(107) is the primary
      attacking site by peroxide, and oxidized Cys(107) reacts with Cys(155)-SH to make
      an intramolecular disulfide bond, which is reduced eventually by Trx. Tryptic
      peptide analysis by matrix-assisted laser desorption and ionization time of
      flight mass spectrometry shows that Cys(155) can form a disulfide bond with
      either Cys(107) or Cys(136).

PMID- 11823461
TI  - DNA polymerase III holoenzyme from Thermus thermophilus identification,
      expression, purification of components, and use to reconstitute a processive
      replicase.
AB  - DNA replication in bacteria is performed by a specialized multicomponent
      replicase, the DNA polymerase III holoenzyme, that consist of three essential
      components: a polymerase, the beta sliding clamp processivity factor, and the
      DnaX complex clamp-loader. We report here the assembly of the minimal functional
      holoenzyme from Thermus thermophilus (Tth), an extreme thermophile. The minimal
      holoenzyme consists of alpha (pol III catalytic subunit), beta (sliding clamp
      processivity factor), and the essential DnaX (tau/gamma), delta and delta'
      components of the DnaX complex. We show with purified recombinant proteins that
      these five components are required for rapid and processive DNA synthesis on long
      single-stranded DNA templates. Subunit interactions known to occur in DNA
      polymerase III holoenzyme from mesophilic bacteria including delta-delta'
      interaction, deltadelta'-tau/gamma complex formation, and alpha-tau interaction,
      also occur within the Tth enzyme. As in mesophilic holoenzymes, in the presence
      of a primed DNA template, these subunits assemble into a stable initiation
      complex in an ATP-dependent manner. However, in contrast to replicative
      polymerases from mesophilic bacteria, Tth holoenzyme is efficient only at
      temperatures above 50 degrees C, both with regard to initiation complex formation
      and processive DNA synthesis. The minimal Tth DNA polymerase III holoenzyme
      displays an elongation rate of 350 bp/s at 72 degrees C and a processivity of
      greater than 8.6 kilobases, the length of the template that is fully replicated
      after a single association event.

PMID- 11823462
TI  - Dynamic equilibrium between coupled and uncoupled modes of a neuronal glutamate
      transporter.
AB  - In the brain, the neurotransmitter glutamate is removed from the synaptic cleft
      by (Na(+) + K(+))-coupled transporters by an electrogenic process. Moreover,
      these transporters mediate a sodium- and glutamate-dependent uncoupled chloride
      conductance. In contrast to the wild type, the uptake of radiolabeled substrate
      by the I421C mutant is inhibited by the membrane-impermeant [2
      (trimethylammonium)ethyl]methanethiosulfonate and also by other sulfhydryl
      reagents. In the wild-type and the unmodified mutant, substrate-induced currents
      are inwardly rectifying and reflect the sum of the coupled electrogenic flux and
      the anion conductance. Remarkably, the I421C mutant modified by sulfhydryl
      reagents exhibits currents that are non-rectifying and reverse at the equilibrium
      potential for chloride. Strikingly, almost 10-fold higher concentrations of d
      aspartate are required to activate the currents in the modified mutant as
      compared with untreated I421C. Under conditions in which only the coupled
      currents are observed, the modified mutant does not exhibit any currents.
      However, when the uncoupled current is dominant, sulfhydryl reagents cause >4
      fold stimulation of this current. Thus, the modification of the cysteine
      introduced at position 421 impacts the coupled but not the uncoupled fluxes.
      Although both fluxes are activated by substrate, they behave as independent
      processes that are in dynamic equilibrium.

PMID- 11823463
TI  - Zinc binding to the NH2-terminal domain of the Wilson disease copper-transporting
      ATPase: implications for in vivo metal ion-mediated regulation of ATPase
      activity.
AB  - Mutations in the Wilson disease copper transporting, P-type ATPase lead to the
      accumulation of toxic levels of copper in the liver, brain, and kidney causing
      extensive tissue damage and eventual death. The NH(2)-terminal domain (
      approximately 70 kDa), which contains six copies of the heavy metal-associated
      repeat GMT/HCXXC, is also able to bind zinc. We have used circular dichroism (CD)
      and x-ray absorption spectroscopy (XAS) to characterize zinc binding to the NH(2)
      terminal metal-binding domain. These studies have revealed that zinc is able to
      bind to this domain with a stoichiometry of 6:1, and upon binding, induces
      conformational changes in the NH(2)-terminal domain. These conformational changes
      are completely different from those previously observed for copper binding to the
      domain and lead to an overall loss of secondary structure in the domain. The XAS
      spectra indicate that zinc is ligated primarily by nitrogen atoms and therefore
      has low affinity for the heavy metal-associated repeats where copper has been
      shown to bind. The differences between zinc and copper binding may serve as the
      basis for the metal-ion mediated regulation of the ATPase in vivo.

PMID- 11823464
TI  - A conserved tryptophan 457 modulates the kinetics and extent of N-hydroxy-L
      arginine oxidation by inducible nitric-oxide synthase.
AB  - In the oxygenase domain of mouse inducible nitric-oxide synthase (iNOSoxy), a
      conserved tryptophan residue, Trp-457, regulates the kinetics and extent of l-Arg
      oxidation to N(omega)-hydroxy-l-arginine (NOHA) by controlling electron transfer
      between bound (6R)-tetrahydrobiopterin (H(4)B) cofactor and the enzyme heme
      Fe(II)O(2) intermediate (Wang, Z. Q., Wei, C. C., Ghosh, S., Meade, A. L.,
      Hemann, C., Hille, R., and Stuehr, D. J. (2001) Biochemistry 40, 12819-12825). To
      investigate whether NOHA oxidation to citrulline and nitric oxide (NO) is
      regulated by a similar mechanism, we performed single turnover reactions with
      wild type iNOSoxy and mutants W457F and W457A. Ferrous proteins containing NOHA
      plus H(4)B or NOHA plus 7,8-dihydrobiopterin (H(2)B), were mixed with O(2)
      containing buffer, and then heme spectral transitions and product formation were
      followed versus time. All three proteins formed a Fe(II)O(2) intermediate with
      identical spectral characteristics. In wild type, H(4)B increased the
      disappearance rate of the Fe(II)O(2) intermediate relative to H(2)B, and its
      disappearance was coupled to the formation of a Fe(III)NO immediate product prior
      to formation of ferric enzyme. In W457F and W457A, the disappearance rate of the
      Fe(II)O(2) intermediate was slower than in wild type and took place without
      detectable build-up of the heme Fe(III)NO immediate product. Rates of Fe(II)O(2)
      disappearance correlated with rates of citrulline formation in all three
      proteins, and reactions containing H(4)B formed 1.0, 0.54, and 0.38
      citrulline/heme in wild type, W457F, and W457A iNOSoxy, respectively. Thus, Trp
      457 modulates the kinetics of NOHA oxidation by iNOSoxy, and this is important
      for determining the extent of citrulline and NO formation. Our findings support a
      redox role for H(4)B during NOHA oxidation to NO by iNOSoxy.

PMID- 11823466
TI  - The Oxa1 protein forms a homooligomeric complex and is an essential part of the
      mitochondrial export translocase in Neurospora crassa.
AB  - The Oxa1 protein is a ubiquitous constituent of the inner membrane of
      mitochondria. Oxa1 was identified in yeast as a crucial component of the protein
      export machinery known as the OXA translocase, which facilitates the integration
      of proteins from the mitochondrial matrix into the inner membrane. We have
      identified the Neurospora crassa Oxa1 protein which shows a sequence identity of
      22% to the yeast homologue. Despite the low level of identity, the function of
      the homologues is conserved as the N. crassa gene fully complemented a yeast null
      mutant. Genetic analysis revealed that Oxa1 is essential for viability in N.
      crassa. Cells propagated under conditions that severely reduce Oxa1 levels grew
      extremely slowly and were deficient in subunits of complex I and complex IV.
      Isolation of the Oxa1 complex from N. crassa mitochondria revealed a 170-180-kDa
      complex that contained exclusively Oxa1. Since the Oxa1 monomer has a molecular
      weight of 43,000, our data suggest that the OXA translocase consists of a
      homooligomer most likely containing four Oxa1 subunits.

PMID- 11823465
TI  - Tumor necrosis factor-alpha converting enzyme (TACE) regulates epidermal growth
      factor receptor ligand availability.
AB  - We previously implicated tumor necrosis factor-alpha converting enzyme
      (TACE/ADAM17) in the processing of the integral membrane precursor to soluble
      transforming growth factor-alpha (TGF-alpha), pro-TGF-alpha. Here we examined TGF
      alpha processing in a physiologically relevant cell model, primary keratinocytes,
      showing that cells lacking TACE activity shed dramatically less TGF-alpha as
      compared with wild-type cultures and that TGF-alpha cleavage was partially
      restored by infection of TACE-deficient cells with TACE-encoding adenovirus.
      Moreover, cotransfection of TACE-deficient fibroblasts with pro-TGF-alpha and
      TACE cDNAs increased shedding of mature TGF-alpha with concomitant conversion of
      cell-associated pro-TGF-alpha to a processed form. Purified TACE accurately
      cleaved pro-TGF-alpha in vitro at the N-terminal site and also cleaved a soluble
      form of pro-TGF-alpha containing only the ectodomain at the C-terminal site. In
      vitro, TACE accurately cleaved peptides corresponding to cleavage sites of
      several epidermal growth factor (EGF) family members, and transfection of TACE
      into TACE-deficient cells increased the shedding of amphiregulin and heparin
      binding EGF (HB-EGF) proteins. Consistent with the hypothesis that TACE regulates
      EGF receptor (EGFR) ligand availability in vivo, mice heterozygous for Tace and
      homozygous for an impaired EGFR allele (wa-2) were born with open eyes
      significantly more often than Tace(+/+)Egfr(wa-2)(/)(wa-2) counterparts.
      Collectively, these data support a broad role for TACE in the regulated shedding
      of EGFR ligands.

PMID- 11823467
TI  - Mutations targeted to a predicted helix in the extreme carboxyl-terminal region
      of the human estrogen receptor-alpha alter its response to estradiol and 4
      hydroxytamoxifen.
AB  - The human estrogen receptor-alpha, a member of the nuclear receptor superfamily,
      is a ligand-regulated transcriptional modulator. Because comparatively little is
      known about the extreme carboxyl-terminal region of the estrogen receptor (F
      domain), we used secondary structure prediction to design mutations that delete
      the F domain (S554stop), disrupt a possible turn (G556L/G557L), and alter a
      predicted helix (S559A/E562A, Q565P), and we evaluated the effects of these
      mutations on hormone binding and transcription activation in response to
      estradiol and the mixed agonist/antagonist 4-hydroxytamoxifen. Mutations that
      deleted the F domain (S554stop) or targeted the predicted helix (S559A/E562A,
      Q565P) greatly reduced or eliminated the agonist activity of 4-hydroxytamoxifen.
      Deleting the F domain increased the affinity of the receptor for estradiol and
      decreased the antagonist activity of 4-hydroxytamoxifen. The Q565P mutant
      exhibited a non-cooperative hormone-binding mechanism, as well as an impaired
      response to estradiol and increased antagonist activity of 4-hydroxytamoxifen.
      Our results show that mutations in the F domain alter not only the response to
      estradiol, the affinity for hormone, and the interaction between receptor
      subunits but can uncouple the agonist and antagonist activities of 4
      hydroxytamoxifen. These results suggest that the F domain modulates the activity
      of the estrogen receptor-alpha by multiple mechanisms.

PMID- 11823468
TI  - Transcriptional regulation of mouse delta-opioid receptor gene. Role of Ikaros in
      the stimulated transcription of mouse delta-opioid receptor gene in activated T
      cells.
AB  - Delta-opioid receptors (DOR) present on T cells have been shown to mediate the
      immunomodulatory effects of endogenous and synthetic DOR agonists on T cells.
      Considerable evidence indicates that there is stimulated transcription of DOR
      gene in activated T cells, which is correlated with augmented expression of DOR
      and enhanced capacity of DOR agonists to affect the T-cell's functions. However,
      the molecular mechanism underlying the stimulated transcription of the DOR gene
      in activated T cells is still unclear. In the present study, we analyzed a 1.3-kb
      DNA fragment immediately upstream of the translation start site (-1300 to +1 bp,
      with the translation start site designated as +1) of the mouse DOR gene in EL-4
      cells, a mouse lymphoma T cell line that exhibits enhanced expression of DOR
      transcripts when activated by phytohemagglutinin. Through both in vivo and in
      vitro experiments, we have demonstrated that increased binding activity of Ikaros
      at the Ikaros-binding site (-378 to -374) in the DOR promoter is required for the
      stimulated transcription of DOR gene in phytohemagglutinin-activated T cells.

PMID- 11823469
TI  - Dye-linked D-proline dehydrogenase from hyperthermophilic archaeon Pyrobaculum
      islandicum is a novel FAD-dependent amino acid dehydrogenase.
AB  - The activity of dye-linked d-proline dehydrogenase was found in the crude extract
      of a hyperthermophilic archaeon, Pyrobaculum islandicum JCM 9189. The dye-linked
      d-proline dehydrogenase was a membrane associated enzyme and was solubilized from
      the membrane fractions by treatment with Tween 20. The solubilized enzyme was
      purified 34-fold in the presence of 0.1% Tween 20 by four sequential
      chromatographies. The enzyme has a molecular mass of about 145 kDa and consisted
      of homotetrameric subunits with a molecular mass of about 42 kDa. The N-terminal
      amino acid sequence of the subunit was MKVAIVGGGIIGLFTAYHLRQQGADVVI. The enzyme
      retained its full activity both after incubation at 80 degrees C for 10 min and
      after incubation in the range of pH 4.0-10.0 at 50 degrees C for 10 min. The
      enzyme-catalyzed dehydrogenation of several d-amino acids was carried out using
      2,6-dichloroindophenol as an electron acceptor, and d-proline was the most
      preferred substrate among the d-amino acids. The Michaelis constants for d
      proline and 2,6-dichloroindophenol were determined to be 4.2 and 0.14 mm,
      respectively. Delta(1)-Pyrroline-2-carboxylate was identified as the reaction
      product from d-proline by thin layer chromatography. The prosthetic group of the
      enzyme was identified to be FAD by high-performance liquid chromatography. The
      gene encoding the enzyme was cloned and expressed in Escherichia coli. The
      nucleotide sequence of the dye-linked d-proline dehydrogenase gene was determined
      and encoded a peptide of 363 amino acids with a calculated molecular weight of
      40,341. The amino acid sequence of the Pb. islandicum enzyme showed the highest
      similarity (38%) with that of the probable oxidoreductase in Sulfolobus
      solfataricus, but low similarity with those of d-alanine dehydrogenases from the
      mesophiles so far reported. This shows that the membrane-bound d-proline
      dehydrogenase from Pb. islandicum is a novel FAD-dependent amino acid
      dehydrogenase.

PMID- 11823470
TI  - Caspase-2 can trigger cytochrome C release and apoptosis from the nucleus.
AB  - The cysteine proteases specific for aspartic residues, known as caspases, are
      localized in different subcellular compartments and play specific roles during
      the regulative and the executive phase of the cell death process. Here we
      investigated the subcellular localization of caspase-2 in healthy cells and
      during the execution of the apoptotic program. We have found that caspase-2 is a
      nuclear resident protein and that its import into the nucleus is regulated by two
      different nuclear localization signals. We have shown that in an early phase of
      apoptosis caspase-2 can trigger mitochondrial dysfunction from the nucleus
      without relocalizing into the cytoplasm. Release of cytochrome c occurs in the
      absence of overt alteration of the nuclear pores and changes of the
      nuclear/cytoplasmic barrier. Addition of leptomycin B, an inhibitor of nuclear
      export, did not interfere with the ability of caspase-2 to trigger cytochrome c
      release. Only during the late phase of the apoptotic process can caspase-2
      relocalize in the cytoplasm, as consequence of an increase in the diffusion
      limits of the nuclear pores. Taken together these data indicate the existence of
      a nuclear/mitochondrial apoptotic pathway elicited by caspase-2.

PMID- 11823471
TI  - Identification of a critical amino acid in the aryl hydrocarbon receptor.
AB  - Two aryl hydrocarbon receptors (rtAHR2alpha and rtAHR2beta) have been identified
      in the rainbow trout (Oncorhynchus mykiss). These receptors share 98% amino acid
      identity, yet their functional properties differ. Both rtAHR2alpha and rtAHR2beta
      bind 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), dimerize with rainbow trout
      ARNTb (rtARNTb), and recognize dioxin response elements in vitro. However, in a
      transient transfection assay the two proteins show differential ability to
      recognize enhancers, produce transactivation, and respond to TCDD. To identify
      the sequence differences that confer the functional differences between
      rtAHR2alpha and rtAHR2beta, we constructed chimeric rtAHRs, in which segments of
      one receptor form was replaced with the corresponding part from the other
      isoform. This approach progressively narrowed the region being examined to a
      single residue, corresponding to position 111 in rtAHR2beta. Altering this
      residue in rtAHR2beta from the lysine to glutamate found in rtAHR2alpha produced
      an rtAHR2beta with the properties of rtAHR2alpha. All other known AHRs resemble
      rtAHR2alpha and carry glutamate at this position, located at the N terminus of
      the PAS-A domain. We tested the effect of altering this glutamate in the human
      and zebrafish AHRs to lysine. This lysine substitution produced AHRs with
      transactivation properties that were similar to rtAHR2beta. These results
      identify a critical residue in AHR proteins that has an important impact on
      transactivation, enhancer site recognition, and regulation by ligand.

PMID- 11823473
TI  - The ATPase, RNA unwinding, and RNA binding activities of recombinant p68 RNA
      helicase.
AB  - p68 RNA helicase, a nuclear RNA helicase, was identified 2 decades ago. The
      protein plays very important roles in cell development and organ maturation.
      However, the biological functions and enzymology of p68 RNA helicase are not well
      characterized. We report the expression and purification of recombinant p68 RNA
      helicase in a bacterial system. The recombinant p68 is an ATP-dependent RNA
      helicase. ATPase assays demonstrated that double-stranded RNA (dsRNA) is much
      more effective than single-stranded RNA in stimulating ATP hydrolysis by the
      recombinant protein. Consistently, RNA-binding assays showed that p68 RNA
      helicase binds single-stranded RNA weakly in an ATP-dependent manner. On the
      other hand, the recombinant protein has very high affinity for dsRNA. Binding of
      the protein to dsRNA is ATP-independent. The data indicate that p68 may directly
      target dsRNA as its natural substrate. Interestingly, the recombinant p68 RNA
      helicase unwinds dsRNA in both 3' --> 5' and 5' --> 3' directions. This is the
      second example of a Asp-Glu-Ala-Asp (DEAD) box RNA helicase that unwinds RNA
      duplexes in a bi-directional manner.

PMID- 11823472
TI  - Requirement for a hsp90 chaperone-dependent MEK1/2-ERK pathway for B cell antigen
      receptor-induced cyclin D2 expression in mature B lymphocytes.
AB  - A requirement for cyclin D2 in G(1)-to-S phase progression has been definitively
      established in mature B cells stimulated via the B cell antigen receptor (BCR).
      However, the identity of constituents of the BCR signaling cascade that leads to
      cyclin D2 accumulation remains incomplete. We report that inhibition of mitogen
      activated protein kinase/extracellular signal-regulated kinase kinase (MEK)-1/2
      blocked BCR-induced activation of extracellular signal-regulated kinase (ERK).
      Inhibition of the MEK1/2-ERK pathway was sufficient to abrogate BCR-induced
      cyclin D2 expression at the mRNA and protein levels. Disruption of endogenous
      heat shock protein 90 (hsp90) function with geldanamycin abrogated BCR-induced
      cyclin D2 expression and proliferation. Geldanamycin effects were attributed to a
      selective depletion of cellular Raf-1 that interrupted BCR-coupled activation of
      MEK1/2 and ERK. By contrast, signaling through the phosphatidylinositol 3-kinase
      and protein kinase C pathways was not affected, suggesting that disruption of
      hsp90 function did not cause a general impairment of BCR signaling. These results
      suggest that the MEK1/2-ERK pathway is essential for BCR signaling to cyclin D2
      accumulation in ex vivo splenic B lymphocytes. Furthermore, these findings imply
      that hsp90 function is required for BCR signaling through the Raf-1-MEK1/2-ERK
      pathway but not through the phosphatidylinositol 3-kinase- or protein kinase C
      dependent pathways.

PMID- 11823474
TI  - Cutting edge: Compartmentalization of Th1-like noninvariant CD1d-reactive T cells
      in hepatitis C virus-infected liver.
AB  - Murine intrahepatic lymphocytes (IHL) are dominated by invariant TCR alpha-chain
      expressing CD1d-reactive NKT cells, which can cause model hepatitis. Invariant
      NKT (CD56(+/-)CD161(+)) and recently identified noninvariant CD1d-reactive T
      cells rapidly produce large amounts of IL-4 and/or IFN-gamma and can regulate
      Th1/Th2 responses. Human liver contains large numbers of CD56(+) NKT cells but
      few invariant NKT. Compared with matched peripheral blood T cell lines, primary
      IHL lines from patients with chronic hepatitis C had high levels of CD161 and
      CD1d reactivity, but the invariant TCR was rare. CD1d-reactive IHL were
      strikingly Th1 biased. IHL also demonstrated CD1d-specific cytotoxic activity.
      Hepatocytes and other liver cells express CD1d. These results identify a novel
      population of human T cells that could contribute to destructive as well as
      protective immune responses in the liver. CD1d-reactive T cells may have distinct
      roles in different tissues.

PMID- 11823475
TI  - Cutting edge: Transcriptional activity of NFATc1 is enhanced by the Pim-1 kinase.
AB  - Pim-1 is an oncogenic serine/threonine kinase implicated in cytokine-induced
      signal transduction and in development of lymphoid malignancies. However, its
      precise function as well as physiological substrates have remained unknown. In
      this study we demonstrate that Pim-1 can physically interact with the NFATc1
      transcription factor and phosphorylate it in vitro on several serine residues. In
      contrast to previously recognized NFATc kinases, wild-type Pim-1 enhances NFATc
      dependent transactivation and IL-2 production in Jurkat T cells, while kinase
      deficient Pim-1 mutants inhibit them in a dominant negative fashion. Our results
      reveal a novel, phosphorylation-dependent regulatory mechanism targeting NFATc1
      through which Pim-1 acts as a downstream effector of Ras to facilitate IL-2
      dependent proliferation and/or survival of lymphoid cells.

PMID- 11823476
TI  - Cutting edge: CD4 and CD8 T cells are intrinsically different in their
      proliferative responses.
AB  - In this study, we compared the proliferation and differentiation of Ag-specific
      CD4 and CD8 T cells following Listeria infection. Our results show that CD4 T
      cells responding to infection divide a limited number of times, with progeny
      exhibiting proliferative arrest in early divisions. Even with increased
      infectious doses, CD4 T cells display this restricted proliferative pattern and
      are not driven to undergo extensive clonal expansion. This is in striking
      contrast to CD8 T cells, which undergo extensive proliferation in response to
      infection. These differences are also evident when CD4 and CD8 T cells receive
      uniform anti-CD3 stimulation in vitro. Together, these results suggest that CD4
      and CD8 T cells are programmed to undergo limited and extensive proliferation,
      respectively, to suit their function as regulator and effector cells.

PMID- 11823477
TI  - Cutting edge: Immune stimulation by neisserial porins is toll-like receptor 2 and
      MyD88 dependent.
AB  - The immunopotentiating activity of neisserial porins, the major outer membrane
      protein of the pathogenic Neisseria, is mediated by its ability to stimulate B
      cells and up-regulate the surface expression of B7-2. This ability is dependent
      on MyD88 and Toll-like receptor (TLR)2 expression, as demonstrated by a lack of a
      response by B cells from MyD88 or TLR2 knockout mice to the porins. Using
      previously described TLR2-dependent reporter constructs, these results were
      confirmed and were shown to be due to induction of NF-kappaB nuclear
      translocation. This is the first demonstration of known vaccine adjuvant to
      stimulate immune cells via TLR2.

PMID- 11823478
TI  - Cutting edge: Tapasin is retained in the endoplasmic reticulum by dynamic
      clustering and exclusion from endoplasmic reticulum exit sites.
AB  - Tapasin retains empty or suboptimally loaded MHC class I molecules in the
      endoplasmic reticulum (ER). However, the molecular mechanism of this process and
      how tapasin itself is retained in the ER are unknown. These questions were
      addressed by tagging tapasin with the cyan fluorescent protein or yellow
      fluorescent protein (YFP) and probing the distribution and mobility of the tagged
      proteins. YFP-tapasin molecules were functional and could be isolated in
      association with TAP, as reported for native tapasin. YFP-tapasin was excluded
      from ER exit sites even after accumulation of secretory cargo due to disrupted
      anterograde traffic. Almost all tapasin molecules were clustered, and these
      clusters diffused freely in the ER. Tapasin oligomers appear to be retained by
      the failure of the export machinery to recognize them as cargo.

PMID- 11823479
TI  - Cutting edge: the toll pathway is required for resistance to gram-positive
      bacterial infections in Drosophila.
AB  - In Drosophila, the response against various microorganisms involves different
      recognition and signaling pathways, as well as distinct antimicrobial effectors.
      On the one hand, the immune deficiency pathway regulates the expression of
      antimicrobial peptides that are active against Gram-negative bacteria. On the
      other hand, the Toll pathway is involved in the defense against filamentous fungi
      and controls the expression of antifungal peptide genes. The gene coding for the
      only known peptide with high activity against Gram-positive bacteria, Defensin,
      is regulated by both pathways. So far, survival experiments to Gram-positive
      bacteria have been performed with Micrococcus luteus and have failed to reveal
      the involvement of one or the other pathway in host defense against such
      infections. In this study, we report that the Toll pathway, but not that of
      immune deficiency, is required for resistance to other Gram-positive bacteria and
      that this response does not involve Defensin.

PMID- 11823480
TI  - Cutting edge: CD8 T cell-mediated demyelination is IFN-gamma dependent in mice
      infected with a neurotropic coronavirus.
AB  - Mice infected with the murine coronavirus, mouse hepatitis virus, strain JHM
      (MHV) develop an immune-mediated demyelinating encephalomyelitis. We showed
      previously that adoptive transfer of MHV-immune splenocytes depleted of either
      CD4 or CD8 T cells to infected RAG1(-/-) recipients (mice deficient in
      recombination activation gene 1) resulted in demyelination. Herein we show that
      transfer of CD8 T cell-enriched splenocytes from MHV-immune IFN-gamma(-/-) donors
      resulted in a substantial decrease in demyelination (4.8% of the white matter of
      the spinal cord compared with 26.3% in those receiving cells from C57BL/6
      donors). Similar numbers of lymphocytes were present in the CNS of recipients of
      either C57BL/6 or IFN-gamma(-/-) CD8 T cells, suggesting that IFN-gamma was not
      crucial for lymphocyte entry into the CNS. Rather, IFN-gamma was critical for
      optimal activation or migration of macrophages or microglia into the white matter
      in the context of CD8 T cell-mediated demyelination.

PMID- 11823481
TI  - Cutting edge: a critical role for IL-10 in induction of nasal tolerance in
      experimental autoimmune myocarditis.
AB  - Appropriate treatment of autoimmune myocarditis following virus infection remains
      a major clinical problem. Induction of nasal tolerance may provide a new approach
      to treatment. However, the exact mechanism of nasal tolerance is unknown. To
      assess the mechanism of nasal tolerance, we examined the role of IL-10 in the
      induction and suppression of autoimmune myocarditis. First we showed that
      blocking IL-10 concurrent with nasal administration of Ag abolished the disease
      suppressing effect of nasal tolerization. It also led to increased cardiac myosin
      specific IL-1 and TNF-alpha production. Then we demonstrated that blocking IL-10
      during the effector phase increased not only the incidence and severity of
      disease but also Ag-specific IL-2, IL-4, and TNF-alpha production as well as
      cardiac myosin-specific IgG1 and IgG2b production, whereas blocking IL-10 during
      the induction phase had no effect. This study implicates IL-10 in the induction
      of nasal tolerance and in limiting inflammation later during the disease process.

PMID- 11823482
TI  - Differential SLP-76 expression and TCR-mediated signaling in effector and memory
      CD4 T cells.
AB  - We present in this study novel findings on TCR-mediated signaling in naive,
      effector, and memory CD4 T cells that identify critical biochemical markers to
      distinguish these subsets. We demonstrate that relative to naive CD4 T cells,
      memory CD4 T cells exhibit a profound decrease in expression of the
      linker/adapter molecule SLP-76, while effector T cells express normal to elevated
      levels of SLP-76. The reduced level of SLP-76 is memory CD4 T cells is coincident
      with reduced phosphorylation overall, yet the residual SLP-76 couples to a subset
      of TCR-associated linker molecules, leading to downstream mitogen-activated
      protein (MAP) kinase activation. By contrast, effector CD4 T cells strongly
      phosphorylate SLP-76, linker for activation of T cells, and additional Grb2
      coupled proteins, exhibit increased associations of SLP-76 to phosphorylated
      linkers, and hyperphosphorylate downstream Erk1/2 MAP kinases. Our results
      suggest distinct coupling of signaling intermediates to the TCR in naive,
      effector, and memory CD4 T cells. Whereas effector CD4 T cells amplify existing
      TCR signaling events accounting for rapid effector responses, memory T cells
      engage fewer signaling intermediates to efficiently link TCR triggering directly
      to downstream MAP kinase activation.

PMID- 11823483
TI  - T-Bet expression and failure of GATA-3 cross-regulation lead to default
      production of IFN-gamma by gammadelta T cells.
AB  - gammadelta T cells predominantly produce IFN-gamma upon activation. To determine
      the basis for default production of IFN-gamma by gammadelta T cells, we analyzed
      the transcription factors T-box expressed in T cells (T-bet) and GATA-3. T-bet,
      absent in naive cells, was induced upon TCR signaling, with IFN-gamma production.
      T-bet also regulated IL-4 synthesis, as gammadelta cells isolated from T-bet
      deficient mice displayed enhanced IL-4 levels with reduced IFN-gamma production.
      Notably, T-bet expression after TCR signaling in gammadelta cells was not down
      regulated by IL-4, in conjunction with a higher ratio of T-bet:GATA-3 expression
      than that found in CD4(+) T cells. Indeed, overexpression of GATA-3 failed to
      inhibit IFN-gamma secretion in gammadelta cells to the degree seen in CD4(+) T
      cells. These results indicate that T-bet enhances IFN-gamma secretion and
      suppresses IL-4 secretion in gammadelta cells, and that GATA-3 fails to
      counterbalance T-bet-mediated IFN-gamma production, accounting for the default
      synthesis of IFN-gamma by these T lymphocytes.

PMID- 11823484
TI  - Up-regulation of drug resistance-related vaults during dendritic cell
      development.
AB  - P-glycoprotein (Pgp) and vaults are associated with multidrug resistance in tumor
      cells, but their physiological functions are not yet clear. Pgp, the prototypical
      transmembrane transporter molecule, may also facilitate the migration of skin
      dendritic cells (DC). Vaults--ribonucleoprotein cell organelles, frequently
      overexpressed in Pgp-negative drug-resistant tumor cells--have also been
      associated with intracellular transport processes. Given the pivotal role of DC
      in dealing with exposure to potentially harmful substances, the present study was
      set out to examine the expression of Pgp and vaults during differentiation and
      maturation of DC. DC were obtained from different sources, including blood
      derived monocytes, CD34(+) mononuclear cells, and chronic myeloid leukemia cells.
      Whereas flow cytometric and immunocytochemical analyses showed slightly augmented
      levels of Pgp, up-regulation of vault expression during DC culturing was strong,
      readily confirmed by Western blotting, and independent of the source of DC. In
      further exploring the functional significance of vault expression, it was found
      that supplementing DC cultures with polyclonal or mAbs against the major vault
      protein led to lower viabilities of LPS- or TNF-alpha-matured monocytes-DC.
      Moreover, expression of critical differentiation, maturation, and costimulatory
      molecules, including CD1a and CD83, was reduced and their capacity to induce Ag
      specific T cell proliferative and IFN-gamma release responses was impaired. These
      data point to a role for vaults in both DC survival and functioning as APC.

PMID- 11823485
TI  - L-selectin-dependent lymphoid occupancy is required to induce alloantigen
      specific tolerance.
AB  - Maneuvers that interfere with signals 1, 2, 3, or Ag processing can result in
      indefinite allograft survival. However, they are not applicable to all tissues,
      strains, or species, suggesting that there are additional levels of immune
      regulation. We hypothesized that secondary lymphoid organs are important for
      interactions among lymphocytes, alloantigen, and immunosuppressants that lead to
      tolerance. To explore this, cardiac allografts were performed with a tolerogenic
      immunosuppressive regimen. Concurrent administration of anti-L-selectin (CD62L)
      Ab, which prevents lymph node homing, prevents indefinite allograft survival and
      tolerance. Anti-CD62L Ab is not costimulatory, and Fab and F(ab')(2) anti-CD62L
      have similar activities. Flow cytometry and histologic examination show that Ab
      shifts T cells away from lymph nodes and into spleen, peripheral blood, and
      graft. Tolerance is not induced in CD62L(-/-) mice, and adoptive transfer of
      CD62L(-/-), but not CD62L(+/+), T cells prevents tolerization in wild-type
      recipients. FTY720, an immunosuppressant that promotes chemokine-dependent, but
      CD62L-independent, lymph node homing, reverses the Ab effect. Blockade of other
      homing receptors also prevents tolerization. These results indicate that T
      lymphocytes use CD62L-dependent migration for alloantigen-specific tolerance, and
      suggest that lymph nodes or other lymphoid tissues are an important site for
      peripheral tolerization to alloantigen.

PMID- 11823486
TI  - Identification and characterization of myeloid translocation gene 16b as a novel
      a kinase anchoring protein in T lymphocytes.
AB  - Increased levels of intracellular cAMP inhibit T cell activation and
      proliferation. One mechanism is via activation of the cAMP-dependent protein
      kinase (PKA). PKA is a broad specificity serine/threonine kinase whose fidelity
      in signaling is maintained through interactions with A kinase anchoring proteins
      (AKAPs). AKAPs are adaptor/scaffolding molecules that convey spatial and temporal
      localization to PKA and other signaling molecules. To determine whether T
      lymphocytes contain AKAPs that could influence the inflammatory response, PBMCs
      and Jurkat cells were analyzed for the presence of AKAPs. RII overlay and cAMP
      pull down assays detected at least six AKAPs. Western blot analyses identified
      four known AKAPs: AKAP79, AKAP95, AKAP149, and WAVE. Screening of a PMA
      stimulated Jurkat cell library identified two additional known AKAPs, AKAP220 and
      AKAP-KL, and one novel AKAP, myeloid translocation gene 16 (MTG16b). Mutational
      analysis identified the RII binding domain in MTG16b as residues 399-420, and
      coimmunoprecipitation assays provide strong evidence that MTG16b is an AKAP in
      vivo. Immunofluorescence and confocal microscopy illustrate distinct subcellular
      locations of AKAP79, AKAP95, and AKAP149 and suggest colocalization of MTG and
      RII in the Golgi. These experiments represent the first report of AKAPs in T
      cells and suggest that MTG16b is a novel AKAP that targets PKA to the Golgi of T
      lymphocytes.

PMID- 11823487
TI  - Prolonged blockade of CD40-CD40 ligand interactions by gene transfer of CD40Ig
      results in long-term heart allograft survival and donor-specific
      hyporesponsiveness, but does not prevent chronic rejection.
AB  - Previous work on blockade of CD40-CD40 ligand interaction in mice and primates
      with anti-CD40 ligand mAbs has resulted in a moderate prolongation of allograft
      survival without the development of true allograft tolerance. In this study, we
      show in rats that adenovirus-mediated gene transfer of CD40Ig sequences into the
      graft resulted in prolonged (>200 days) expression of CD40Ig and in long-term
      (>300 days) survival. Recipients expressing CD40Ig displayed strongly (>90%)
      inhibited mixed leukocyte reactions and alloantibody production at early (days 5
      and 17) and late time points (>100 day) after transplantation, but showed limited
      inhibition of leukocyte infiltration and cytokine production as evaluated by
      immunohistology at early time points (day 5). Recipients of long-surviving hearts
      showed donor-specific hyporesponsiveness since acceptance of second cardiac
      allografts was donor specific. Nevertheless, long-term allografts (>100 days)
      displayed signs of chronic rejection vasculopathy. Occluded vessels showed
      leukocyte infiltration, mainly composed of CD4(+) and CD8(+) cells, macrophages,
      and mast cells. These recipients also showed antidonor CTL activity. Recipients
      expressing CD40Ig did not show nonspecific immunosuppression, as they were able
      to mount anticognate immune responses that were partially inhibited at early time
      points and were normal thereafter. We conclude that gene transfer-mediated
      expression of CD40Ig resulted in a highly efficient inhibition of acute heart
      allograft rejection in rats. This treatment induced donor-specific inhibition of
      certain alloreactive mechanisms in the short-, but not the long-term, which
      resulted in long-term survival of allografts concomitant with the development of
      chronic rejection.

PMID- 11823488
TI  - Preferential Th1 immune response in invariant chain-deficient mice.
AB  - MHC class II molecules associate with the invariant chain (Ii) molecule during
      biosynthesis. Ii facilitates the folding of class II molecules, interferes with
      their peptide association, and is involved in MHC class II transport. In this
      study, we have investigated the in vitro and in vivo immune response of Ii
      deficient mice (Ii(-/-)). Our results have demonstrated that CD4(+) T cells from
      Ii(-/-) mice proliferate normally in vitro after in vivo immunization with
      protein Ags. However, cytokine secretion profiles of Ag-primed CD4(+) T cells
      from Ii(-/-) mice differ from CD4(+) T cells from wild-type mice. Whereas cells
      from wild-type mice secrete IFN-gamma and IL-4, cells from Ii(-/-) mice secrete
      mostly IFN-gamma. Moreover, Ii(-/-) mice exhibit a normal Th1 response in the
      delayed-type hypersensitivity and trinitrobenzene sulfonic acid colitis models;
      however, these mice lack an in vivo Th2 response, as demonstrated in the asthma
      model. Therefore, we suggest that defective Ag presentation in Ii(-/-) mice leads
      selectively to a Th1 effector response.

PMID- 11823489
TI  - Vascular endothelial-junctional adhesion molecule (VE-JAM)/JAM 2 interacts with
      T, NK, and dendritic cells through JAM 3.
AB  - Screening expressed sequence tag databases for endothelial-specific homologs to
      human junctional adhesion molecule (JAM) and A33-Ag, we identified a protein of
      298 aa that represents the recently described vascular endothelial-JAM (VE
      JAM)/JAM 2. We confirmed VE-JAM/JAM 2 expression to be restricted to the high
      endothelial venule of tonsil and lymph nodes, and we further expanded the
      localization to the endothelium of arterioles in and around inflammatory and
      tumor foci. In our functional characterizations of VE-JAM/JAM 2, we discovered
      that it can function as an adhesive ligand for the T cell line J45 and can
      interact with GM-CSF/IL-4-derived peripheral blood dendritic cells, circulating
      CD56(+) NK cells, circulating CD56(+)CD3(+) NK/T cells, and circulating
      CD56(+)CD3(+)CD8(+) cytolytic T cells. In the course of our studies, we also
      isolated and characterized the functional VE-JAM/JAM 2 receptor, which, upon
      cloning, turned out to be a submitted sequence representing JAM 3 (accession
      number NP 113658). With these understandings, we have characterized a protein
      interacting pair that can be important in the role of T, NK, and dendritic cell
      trafficking and inflammation.

PMID- 11823490
TI  - Inhibitory effects of apoptotic cell ingestion upon endotoxin-driven myeloid
      dendritic cell maturation.
AB  - Dendritic cells (DCs) are the sentinels of the immune system, able to interact
      with both naive and memory T cells. The recent observation that DCs can ingest
      cells dying by apoptosis has raised the possibility that DCs may, in fact,
      present self-derived Ags, initiating both autoimmunity and tumor-specific
      responses, especially if associated with appropriate danger signals. Although the
      process of ingestion of apoptotic cells has not been shown to induce DC
      maturation, the exact fate of these phagocytosing DCs remains unclear. In this
      paper we demonstrate that DCs that ingest apoptotic cells are able to produce TNF
      alpha but have a diminished ability to produce IL-12 in response to external
      stimuli, a property that corresponds to a failure to up-regulate CD86. By single
      cell analysis we demonstrate that these inhibitory effects are restricted to
      those DCs that have engulfed apoptotic cells, with bystander DCs remaining
      unaffected. These changes were independent of the production of anti-inflammatory
      cytokines TGF-beta1 and IL-10 and corresponded with a diminished capacity to
      stimulate naive T cells. Thus, the ingestion of apoptotic cells is not an
      immunologically null event but is capable of modulating DC maturation. These
      results have important implications for our understanding of the role of
      clearance of dying cells by DCs not only in the normal resolution of inflammation
      but also in control of subsequent immune responses to apoptotic cell-derived Ags.

PMID- 11823491
TI  - CD8(+), alphabeta-TCR(+), and gammadelta-TCR(+) cells in the recipient
      hematopoietic environment mediate resistance to engraftment of allogeneic donor
      bone marrow.
AB  - Historically, conditioning for engraftment of hematopoietic stem cells has been
      nonspecific. In the present study, we characterized which cells in the recipient
      hematopoietic microenvironment prevent allogeneic marrow engraftment. Mice
      defective in production of alphabeta-TCR(+), gammadelta-TCR(+), alphabeta- plus
      gammadelta-TCR(+), CD8(+), or CD4(+) cells were transplanted with MHC-disparate
      allogeneic bone marrow. Conditioning with 500 cGy total body irradiation (TBI)
      plus a single dose of cyclophosphamide (CyP) on day +2 establishes chimerism in
      normal recipients. When mice were conditioned with 300 cGy TBI plus a single dose
      of CyP on day +2, all engrafted, except wild-type controls and those defective in
      production of CD4(+) T cells. Mice lacking both alphabeta- and gammadelta-TCR(+)
      cells engrafted without conditioning, suggesting that both alphabeta- and
      gammadelta-TCR T cells in the host play critical and nonredundant roles in
      preventing engraftment of allogeneic bone marrow. CD8 knockout (KO) mice
      engrafted without TBI, but only if they received CyP on day +2 relative to the
      marrow infusion, showing that a CD8(-) cell was targeted by the CyP conditioning.
      The CD8(+) cell effector function is mechanistically different from that for
      conventional T cells, and independent of CD4(+) T helper cells because CD4 KO
      mice require substantially higher levels of conditioning than the other KO
      phenotypes. These results suggest that a number of cell populations with
      different mechanisms of action mediate resistance to engraftment of allogeneic
      marrow. Targeting of specific recipient cellular populations may permit
      conditioning approaches to allow mixed chimerism with minimal morbidity and could
      potentially avoid the requirement for myelotoxic agents altogether.

PMID- 11823492
TI  - Preferential recognition of self antigens despite normal thymic deletion of
      CD4(+)CD25(+) regulatory T cells.
AB  - T cell tolerance to self Ags is in part established in the thymus by induction of
      apoptosis or anergy of potentially autoreactive thymocytes. Some autospecific T
      cells nevertheless migrate to peripheral lymphoid organs but are kept under
      control by the recently identified CD4(+)CD25(+) regulatory T cell subset.
      Because these cells inhibit autoimmunity more efficiently than useful non-self Ag
      specific immune responses, they are probably autospecific, posing important
      questions as to how they develop in the thymus. In this study we show that
      significantly more peripheral CD4(+)CD25(+) regulatory T cells recognize self
      than non-self Ags. However, we also show for a large panel of endogenous
      superantigens as well as for self peptide/MHC complexes that autospecific
      CD4(+)CD25(+) thymocyte precursors are normally deleted during ontogeny.
      Combined, our data firmly establish that the repertoire of regulatory T cells is
      specifically enriched in autospecific cells despite the fact that their
      precursors are normally susceptible to thymic deletion.

PMID- 11823493
TI  - Early growth response transcription factors are required for development of CD4(
      )CD8(-) thymocytes to the CD4(+)CD8(+) stage.
AB  - Progression of immature CD4(-)CD8(-) thymocytes beyond the beta-selection
      checkpoint to the CD4(+)CD8(+) stage requires activation of the pre-TCR complex;
      however, few of the DNA-binding proteins that serve as molecular effectors of
      those pre-TCR signals have been identified. We demonstrate in this study that
      members of the early growth response (Egr) family of transcription factors are
      critical effectors of the signals that promote this developmental transition.
      Specifically, the induction of three Egr family members (Egr1, 2, and 3)
      correlates with pre-TCR activation and development of CD4(-)CD8(-) thymocytes
      beyond the beta-selection checkpoint. Enforced expression of each of these Egr
      factors is able to bypass the block in thymocyte development associated with
      defective pre-TCR function. However, Egr family members may play somewhat
      distinct roles in promoting thymocyte development, because there are differences
      in the genes modulated by enforced expression of particular Egr factors. Finally,
      interfering with Egr function using dominant-negative proteins disrupts thymocyte
      development from the CD4(-)CD8(-) to the CD4(+)CD8(+) stage. Taken together,
      these data demonstrate that the Egr proteins play an essential role in executing
      the differentiation program initiated by pre-TCR signaling.

PMID- 11823494
TI  - CpG oligodeoxynucleotides as vaccine adjuvants in primates.
AB  - Synthetic oligodeoxynucleotides (ODN) containing unmethylated CpG motifs act as
      immune adjuvants in mice, boosting the humoral and cellular response to
      coadministered Ags. CpG ODN that stimulate human PBMC are only weakly active in
      mice. Thus, alternative animal models are needed to monitor the activity and
      safety of "human" CpG ODN in vivo. This work demonstrates that rhesus macaques
      recognize and respond to the same CpG motifs that trigger human immune cells.
      Coadministering CpG ODN with heat-killed Leishmania vaccine provided
      significantly increased protection of macaques against cutaneous Leishmania
      infection. These findings indicate that rhesus macaques provide a useful model
      for studying the in vivo activity of human CpG motifs, and that ODN expressing
      these motifs act as strong immune adjuvants.

PMID- 11823495
TI  - Quantitative and qualitative adjustment of thymic T cell production by clonal
      expansion of premigrant thymocytes.
AB  - In normal mice, single-positive thymocytes proliferate before being exported into
      the peripheral T cell pool. We measured the in vivo proliferation rates of mature
      thymocytes in several TCR transgenic mice. Different monoclonal TCR transgenic
      single-positive thymocytes proliferated at different rates in a given MHC
      context. Conversely, mature thymocytes expressing a given TCR, generated in mice
      of different MHC haplotypes, also showed different rates of proliferation. In
      p59(fyn)-deficient mice, the proliferation rate of mature thymocytes was
      diminished. Thus, premigrant thymocyte expansion is TCR mediated and depends on
      TCR affinity for self peptide/MHC ligands. In addition, we show that mature
      thymocyte expansion is clonotypic, increases the daily thymic T cell output, and
      modifies the TCR repertoire of newly produced T cells.

PMID- 11823497
TI  - Continued antigen stimulation is not required during CD4(+) T cell clonal
      expansion.
AB  - Peptide Ag initiates CD4(+) T cell proliferation, but the subsequent effects of
      Ag on clonal expansion are not fully known. In this study, murine CD4(+) T cells
      were labeled with the fluorescent dye CFSE and were stimulated with specific
      peptide Ag. Activation occurred, as CFSE-associated fluorescence was reduced 2
      fold with each cell division. Separation of proliferating cells based upon CFSE
      fluorescence intensity showed that daughter cells from each cell division
      proliferate even after removal of Ag. A limited exposure (2 h) to peptide
      programmed the cells to proliferate independently of Ag. Although not required
      for cell division, Ag increased the survival of proliferating cells and increased
      the total number of cell divisions in the expansion process. These results
      indicate that Ag exposure begins a program of cell division that does not require
      but is modified by further TCR stimulation.

PMID- 11823496
TI  - A clonal culture system demonstrates that IL-4 induces a subpopulation of
      noncytolytic T cells with low CD8, perforin, and granzyme expression.
AB  - Immune deviation of cytolytic T cell function, induced by type 2 cytokines like
      IL-4, is an attractive concept to explain failure of the immune system in some
      diseases. However, this concept is challenged by previous conflicting results on
      whether type 2 cytokine-producing CD8(+) T cells are cytolytic. Therefore, we
      have analyzed the relationship between cytolytic activity and cytokine production
      among large numbers of primary CD8(+) T cell clones. Single murine CD8(+) T cells
      of naive phenotype were activated at high efficiency with immobilized Abs to CD3,
      CD8, and CD11a in the presence of IL-2 (neutral conditions) or IL-2, IL-4, and
      anti-IFN-gamma Ab (type 2-polarizing conditions) for 8-9 days. Under neutral
      conditions, most clones produced IFN-gamma without IL-4 and were cytolytic. Under
      type 2-polarizing conditions, most clones produced IFN-gamma and IL-4 but
      displayed variable cytolytic activity and CD8 expression. Separation on the basis
      of surface CD8 levels revealed that, compared with CD8(high) cells from the same
      cultures, CD8(low) cells were poorly cytolytic and expressed low levels of
      perforin mRNA and protein and granzyme A, B, and C mRNA. A similar, smaller
      population of noncytolytic CD8(low) cells was identified among CD8(+) T cells
      activated in mixed lymphocyte reaction with IL-4. Variable efficiency of
      generation of the noncytolytic cells may account for the differing results of
      earlier studies. We conclude that IL-4 promotes the development of a noncytolytic
      CD8(low) T cell phenotype that might be important in tumor- or pathogen-induced
      immune deviation.

PMID- 11823498
TI  - Obligatory requirement of sulfation for P-selectin binding to human salivary
      gland carcinoma Acc-M cells and breast carcinoma ZR-75-30 cells.
AB  - Stimulated endothelial cells and activated platelets express P-selectin, which
      reacts with P-selectin glycoprotein ligand-1 (PSGL-1) for leukocyte rolling on
      the stimulated endothelial cells and heterotypic aggregation of the activated
      platelets on leukocytes. P-selectin also binds to several cancer cells in vitro
      and promotes the growth and metastasis of human colon carcinoma in vivo. The P
      selectin/PSGL-1 interaction requires tyrosine sulfation. However, it is unknown
      whether sulfation is necessary for P-selectin binding to somatic cancer cells. In
      this study, we show that P-selectin mediated adhesion of Acc-M cells, a cell line
      derived from a human adenoid cystic carcinoma of salivary gland. These cells had
      a moderate expression of heparan sulfate-like proteoglycans, but had no
      detectable expressions of PSGL-1, CD24, Lewis(x), and sialyl Lewis(x). Treatment
      with sodium chlorate (a sulfation biosynthesis inhibitor), but not 4
      methylumbelliferyl-beta-D-xyloside (a proteoglycan biosynthesis inhibitor) or
      heparinases, reduced adhesion of these cells to P-selectin. Sodium chlorate also
      inhibited the P-selectin precipitation of the 160-, 54-, and 36-kDa molecules
      from the cell surface of Acc-M cells. Furthermore, P-selectin could bind to human
      breast carcinoma ZR-75-30 cells in a sulfation-dependent manner. Our results thus
      indicate that sulfation is essential for adhesion of nonblood-borne, epithelial
      like human cancer cells to P-selectin.

PMID- 11823499
TI  - Minor histocompatibility antigen-specific MHC-restricted CD8 T cell responses
      elicited by heat shock proteins.
AB  - In mammals, the heat shock proteins (HSP) gp96 and hsp70 elicit potent specific
      MHC class I-restricted CD8(+) T cell (CTL) response to exogenous peptides they
      chaperone. We show in this study that in the adult frog Xenopus, a species whose
      common ancestors with mammals date back 300 million years, both hsp70 and gp96
      generate an adaptive specific cellular immune response against chaperoned minor
      histocompatibility antigenic peptides that effects an accelerated rejection of
      minor histocompatibility-locus disparate skin grafts in vivo and an MHC-specific
      CD8(+) cytotoxic T cell response in vitro. In naturally class I-deficient but
      immunocompetent Xenopus larvae, gp96 also generates an antitumor immune response
      that is independent of chaperoned peptides (i.e., gp96 purified from normal
      tissue also generates a significant antitumor response); this suggests a
      prominent contribution of an innate type of response in the absence of MHC class
      I Ags.

PMID- 11823500
TI  - Microbial compounds selectively induce Th1 cell-promoting or Th2 cell-promoting
      dendritic cells in vitro with diverse th cell-polarizing signals.
AB  - Upon microbial infection, specific Th1 or Th2 responses develop depending on the
      type of microbe. Here, we demonstrate that different microbial compounds polarize
      the maturation of human myeloid dendritic cells (DCs) into stably committed Th1
      cell-promoting (DC1) or Th2 cell-promoting (DC2) effector DCs that polarize Th
      cells via different mechanisms. Protein extract derived from the helminth
      Schistosoma mansoni induced the development of DC2s that promote the development
      of Th2 cells via the enhanced expression of OX40 ligand. Likewise, toxin from the
      extracellular bacterium Vibrio cholerae induced development of DC2s as well,
      however, via an OX40 ligand-independent, still unknown mechanism. In contrast,
      toxin from the intracellular bacterium Bordetella pertussis induced the
      development of DC1s with enhanced IL-12 production, which promotes a Th1 cell
      development. Poly(I:C) (dsRNA, mimic for virus) induced the development of
      extremely potent Th1-inducing DC1, surprisingly, without an enhanced IL-12
      production. The obtained DC1s and DC2s are genuine effector cells that stably
      express Th cell-polarizing factors and are unresponsive to further modulation.
      The data suggest that the molecular basis of Th1/Th2 polarization via DCs is
      unexpectedly diverse and is adapted to the nature of the microbial compounds.

PMID- 11823501
TI  - Intercellular adhesion molecule-1/LFA-1 ligation favors human Th1 development.
AB  - Th cell polarization toward Th1 or Th2 cells is strongly driven by exogenous
      cytokines, in particular IL-12 or IL-4, if present during activation by Ag
      presenting dendritic cells (DC). However, additional Th cell polarizing
      mechanisms are induced by the ligation of cell surface molecules on DC and naive
      Th cells. In the present study, the role of LFA-1/ICAM-1 ligation in human Th
      cell polarization was investigated. Triggering of LFA-1 on anti-CD3/CD28
      stimulated naive Th cells with immobilized Fc-ICAM-1, in the absence of DC and
      exogenous cytokines, induced a marked shift toward Th1 cell development,
      accompanied by a dose-dependent decrease in GATA-3 expression and a dose
      dependent increase in T-bet expression. Th1 polarization by LFA-1 ligation could
      be demonstrated only under low cytokine conditions, as it was largely overruled
      by IL-12 or IL-4. This IL-12-independent Th1-driving mechanism appears to be
      operated by certain subsets of effector DC. Maturation of DC by poly(I:C), a
      synthetic dsRNA, used as an in vitro model for viral infections, leads to the
      generation of Th1-driving effector DC (DC1), which express elevated levels of
      ICAM-1 but produce only low levels of IL-12p70. Blocking the ICAM-1/LFA-1
      interaction in cocultures of these DC with naive Th cells attenuated their Th1
      driving capacity. The molecular mechanism by which LFA-1 signaling supports Th1
      differentiation is blocked by specific inhibitors of extracellular signal
      regulated kinase phosphorylation. The present data indicate the existence of an
      IL-12-independent, extracellular signal-regulated kinase-mediated mechanism,
      through which high ICAM-1-expressing DC1 can drive Th1 polarization. This
      mechanism may be operational during viral infections.

PMID- 11823502
TI  - Proteasome-assisted identification of a SSX-2-derived epitope recognized by tumor
      reactive CTL infiltrating metastatic melanoma.
AB  - The tumor Ag SSX-2 (HOM-MEL-40) was found by serological identification of Ags by
      recombinant expression cloning and was shown to be a cancer/testis Ag expressed
      in a wide variety of tumors. It may therefore represent a source of CD8(+) T cell
      epitopes useful for specific immunotherapy of cancer. To identify potential SSX-2
      derived epitopes that can be recognized by CD8(+) T cells, we used an approach
      that combined: 1) the in vitro proteasomal digestion of precursor peptides
      overlapping the complete SSX-2 sequence; 2) the prediction of SSX-2-derived
      peptides with an appropriate HLA-A2 binding score; and 3) the analysis of a tumor
      infiltrated lymph node cell population from an HLA-A2(+) melanoma patient with
      detectable anti-SSX-2 serum Abs. This strategy allowed us to identify peptide SSX
      2(41-49) as an HLA-A2-restricted epitope. SSX2(41-49)-specific CD8(+) T cells
      were readily detectable in the tumor-infiltrated lymph node population by
      multimer staining, and CTL clones isolated by multimer-guided cell sorting were
      able to lyse HLA-A2(+) tumor cells expressing SSX-2.

PMID- 11823503
TI  - Repeated antigen exposure is necessary for the differentiation, but not the
      initial proliferation, of naive CD4(+) T cells.
AB  - The mechanisms that regulate CD4(+) T cells responses in vivo are still poorly
      understood. We show here that initial Ag stimulation induces in CD4(+) T cells a
      program of proliferation that can develop, for at least seven cycles of division,
      in the absence of subsequent Ag or cytokine requirement. Thereafter,
      proliferation stops but can be reinitiated by novel Ag stimulation. This initial
      Ag stimulation does not however suffice to induce the differentiation of naive
      CD4(+) T cells into effector Th1 cells which requires multiple contacts with Ag
      loaded APC. Thus, recurrent exposure to both Ag and polarizing cytokines appears
      to be essential for the differentiation of IFN-gamma-producing cells. Ag and
      cytokine availability therefore greatly limits the differentiation, but not the
      initial proliferation, of CD4(+) T cells into IFN-gamma-producing cells.

PMID- 11823504
TI  - Cholera toxin B pretreatment of macrophages and monocytes diminishes their
      proinflammatory responsiveness to lipopolysaccharide.
AB  - The cholera toxin B chain (CTB) has been reported to suppress T cell-dependent
      autoimmune diseases and to potentiate tolerance of the adaptive immune system. We
      have analyzed the effects of CTB on macrophages in vitro and have found that
      preincubation with CTB (10 microg/ml) suppresses the proinflammatory reaction to
      LPS challenge, as demonstrated by suppressed production of TNF-alpha, IL-6, IL
      12(p70), and NO (p < 0.01) in cells of macrophage lines. Pre-exposure to CTB also
      suppresses LPS-induced TNF-alpha and IL-12(p70) formation in human PBMC. Both
      native and recombinant CTB exhibited suppressive activity, which was shared by
      intact cholera toxin. In cells of the human monocyte line Mono Mac 6, exposure to
      CTB failed to suppress the production of IL-10 in response to LPS. Control
      experiments excluded a role of possible contamination of CTB by endotoxin or
      intact cholera toxin. The suppression of TNF-alpha production occurred at the
      level of mRNA formation. Tolerance induction by CTB was dose and time dependent.
      The suppression of TNF-alpha and IL-6 production could be counteracted by the
      addition of Abs to IL-10 and TGF-beta. IFN-gamma also antagonized the actions of
      CTB on macrophages. In contrast to desensitization by low doses of LPS, tolerance
      induction by CTB occurred silently, i.e., in the absence of a measurable
      proinflammatory response. These findings identify immune-deviating properties of
      CTB at the level of innate immune cells and may be relevant to the use of CTB in
      modulating immune-mediated diseases.

PMID- 11823505
TI  - Notch1 perturbation of hemopoiesis involves non-cell- autonomous modifications.
AB  - To study the effects of Notch on hemopoiesis we used a bone marrow
      transduction/transplantation model and compared the transduced and nontransduced
      populations in reconstituted mice. While cells expressing a constitutively active
      form of murine Notch1 (Notch1IC) completely lacked B cells, a profound
      suppression of the B lineage was also seen in the nontransduced compartment.
      Experiments performed with retroviral supernatants of varying titers showed that
      the perturbations of B cell development among the nontransduced population
      correlated with the percentage of Notch1IC-transduced cells inoculated into the
      mice. The myeloid lineage of the Notch1IC-transplanted mice was altered as well,
      and this also affected the nontransduced population that had features of
      excessive maturation. To explore the basis of these non-cell-autonomous
      modifications we prepared conditioned medium from ex vivo cultures of Notch1IC
      transplanted mice bone marrow and showed that it inhibited B cell maturation and
      promoted myeloid differentiation in a dose-dependent manner. Finally, we found
      that the T cell leukemia/lymphomas that occur in Notch1IC-transplanted mice were
      accompanied by abnormal maturation of nontransduced T cells in the bone marrow.
      These findings indicate that modifications of neighboring cells through non-cell
      autonomous modifications take part in multiple facets of the activity of Notch on
      hemopoiesis.

PMID- 11823506
TI  - Impaired NK cell development in an IFN-gamma transgenic mouse: aberrantly
      expressed IFN-gamma enhances hematopoietic stem cell apoptosis and affects NK
      cell differentiation.
AB  - Aberrant expression of IFN-gamma has been demonstrated to cause a wide variety of
      alterations in cell function and development. Previously we reported that
      constitutive expression of IFN-gamma in bone marrow (BM) and thymus results in a
      total absence of B cells and a substantial decrease in the number of
      hematopoietic progenitor cells. In this study, we demonstrate a severe deficiency
      of NK1.1(+)CD3(-) cells in this transgenic mouse model. Compared with normal
      control littermates, we found a pronounced reduction of NK cells in IFN-gamma
      transgenic mouse spleen and liver despite maintenance of normal function. In
      addition, we observed a reduced number of BM cells in the IFN-gamma transgenic
      mouse despite normal expression of hematopoietic growth factors in the BM.
      Interestingly, these cells were less responsive to stem cell factor (SCF) despite
      c-kit expression on hematopoietic stem cells (HSCs). We observed that addition of
      exogenous IFN-gamma inhibited proliferation of HSCs and differentiation of NK
      precursors from HSCs in normal mice in response to SCF, IL-7, fms-like tyrosine
      kinase 3 ligand, and IL-15. Furthermore, we found that HSCs express the IFN
      gammaRalpha subunit and undergo apoptosis in response to exogenous IFN-gamma.
      Thus, we have demonstrated the occurrence of a severe deficiency of NK cells and
      lower numbers of BM cells in an IFN-gamma transgenic mouse model. Furthermore,
      because exogenous IFN-gamma affects the responsiveness to hematopoietic growth
      factors such as SCF in vitro, our results indicate that chronic expression of IFN
      gamma in vivo leads to widespread immune system defects, including alterations in
      NK cell differentiation.

PMID- 11823507
TI  - In vivo dehydroepiandrosterone restores age-associated defects in the protein
      kinase C signal transduction pathway and related functional responses.
AB  - Elderly subjects are at increased risk of pneumonia, influenza, and tuberculosis.
      Besides the known age-related decrease in mechanisms for mechanical clearance of
      the lungs, impaired alveolar macrophage function contributes to the increased
      risk of illness in the elderly. We have previously shown that age-induced
      macrophage immunodeficiencies are associated with a defective system for
      anchoring protein kinase C. Castration of young male rats produces effects on
      alveolar macrophages similar to those of aging, suggesting a relationship between
      circulating sex hormones, particularly androgens, and the decreases in the
      receptor for activated C kinase (RACK-1) and macrophage function observed. The
      aging process in humans and rats is associated with a decline in the plasma
      concentrations of dehydroepiandrosterone (DHEA) and its sulfate, among other
      steroid hormones. We report here that in vitro and in vivo administration of DHEA
      to rats restores the age-decreased level of RACK-1 and the LPS-stimulated
      production of TNF-alpha in alveolar macrophages. DHEA in vivo also restores age
      decreased spleen mitogenic responses and the level of RACK-1 expression. These
      findings suggest that the age-related loss in immunological responses, linked to
      defective pathways of signal transduction, are partially under hormonal control
      and can be restored by appropriate replacement therapy.

PMID- 11823508
TI  - Distinct role of p38 and c-Jun N-terminal kinases in IL-10-dependent and IL-10
      independent regulation of the costimulatory molecule B7.2 in lipopolysaccharide
      stimulated human monocytic cells.
AB  - The costimulatory molecule B7.2 (CD86) plays a vital role in immune activation
      and development of Th responses. The molecular mechanisms by which B7.2
      expression is regulated are not understood. We investigated the role of mitogen
      activated protein kinases (MAPK) in the regulation of B7.2 expression in LPS
      stimulated human monocytic cells. LPS stimulation of human monocytes resulted in
      the down-regulation of B7.2 expression that could be abrogated by anti-IL-10 Abs.
      Furthermore, SB202190, a specific inhibitor of p38 MAPK, inhibited LPS-induced IL
      10 production and reversed B7.2 down-regulation, suggesting that LPS-induced B7.2
      down-regulation may be mediated, at least in part, via regulation of IL-10
      production by p38 MAPK. In contrast to human promonocytic THP-1 cells that are
      refractory to the inhibitory effects of IL-10, LPS stimulation enhanced B7.2
      expression. This IL-10-independent B7.2 induction was not influenced by specific
      inhibitors of either p38 or p42/44 MAPK. To ascertain the role of the c-Jun N
      terminal kinase (JNK) MAPK, dexamethasone, an inhibitor of JNK activation, was
      used, which inhibited LPS-induced B7.2 expression. Transfection of THP-1 cells
      with a plasmid expressing a dominant-negative stress-activated
      protein/extracellular signal-regulated kinase kinase 1 significantly reduced LPS
      induced B7.2 expression, thus confirming the involvement of JNK. To study the
      signaling events downstream of JNK activation, we show that dexamethasone did not
      inhibit LPS-induced NF-kappaB activation in THP-1 cells, suggesting that JNK may
      not be involved in NF-kappaB activation leading to B7.2 expression. Taken
      together, our results reveal the distinct involvement of p38 in IL-10-dependent,
      and JNK in IL-10-independent regulation of B7.2 expression in LPS-stimulated
      monocytic cells.

PMID- 11823509
TI  - Inhibitor of apoptosis protein from Orgyia pseudotsugata nuclear polyhedrosis
      virus provides a costimulatory signal required for optimal proliferation of
      developing thymocytes.
AB  - The inhibitors of apoptosis proteins (IAPs) constitute a family of endogenous
      inhibitors that control apoptosis in the cell by inhibiting caspase processing
      and activity. IAPs are also implicated in cell division, cell cycle regulation,
      and cancer. To address the role of IAPs in thymus development and homeostasis, we
      generated transgenic mice expressing IAP generated from the baculovirus Orgyia
      pseudotsugata nuclear polyhedrosis virus (OpIAP). Developing thymocytes
      expressing OpIAP show increased nuclear levels of NF-kappaB and reduced
      cytoplasmic levels of its inhibitor, IkappaBalpha. In mature thymocytes, OpIAP
      induces optimal activation and proliferation after TCR triggering in the absence
      of a costimulatory signal. OpIAP expression in immature thymocytes blocks TCR
      induced apoptosis. Taken together, our data illustrate the pleiotropism of OpIAP
      in vivo.

PMID- 11823511
TI  - Mutagenesis within human FcepsilonRIalpha differentially affects human and murine
      IgE binding.
AB  - Soluble fragments of the alpha-chain of FcepsilonRI, the high-affinity receptor
      for IgE, compete with membrane-bound receptors for IgE and may thus provide a
      means to combat allergic responses. Mutagenesis within FcepsilonRIalpha is used
      in this study, in conjunction with the crystal structure of the
      FcepsilonRIalpha/IgE complex, to define the relative importance of specific
      residues within human FcepsilonRIalpha for IgE binding. We have also compared the
      effects of these mutants on binding to both human and mouse IgE, with a view to
      evaluating the mouse as an appropriate model for the analysis of future agents
      designed to mimic the human FcepsilonRIalpha and attenuate allergic disease.
      Three residues within the C-C' region of the FcepsilonRIalpha2 domain and two
      residues within the alpha2 proximal loops of the alpha1 domain were selected for
      mutagenesis and tested in binding assays with human and mouse IgE. All three
      alpha2 mutations (K117D, W130A, and Y131A) reduced the affinity of human IgE
      binding to different extents, but K117D had a far more pronounced effect on mouse
      IgE binding, and although Y131A had little effect, W130A modestly enhanced
      binding to mouse IgE. The mutations in alpha1 (R15A and F17A) diminished binding
      to both human and mouse IgE, with these effects most likely caused by disruption
      of the alpha1/alpha2 interface. Our results demonstrate that the effects of
      mutations in human FcepsilonRIalpha on mouse IgE binding, and hence the
      inhibitory properties of human receptor-based peptides assayed in rodent models
      of allergy, may not necessarily reflect their activity in a human IgE-based
      system.

PMID- 11823510
TI  - Class II transactivator is required for maximal expression of HLA-DOB in B cells.
AB  - HLA-DO, encoded by the HLA-DOA and HLA-DOB genes, has been shown to function as a
      modulator of Ag presentation. DNA microarray comparisons between B cells wild
      type and mutant for the master regulator of MHC class II transcription, class II
      transactivator (CIITA), identified HLA-DOA and HLA-DOB as being up-regulated by
      CIITA. Although HLA-DOA had been shown previously to be regulated by CIITA, HLA
      DOB expression was suggested to be independent of CIITA. A series of assays
      including quantitative RT-PCR, promoter-reporter assays, chromatin
      immunoprecipitations, and intracellular staining were performed to corroborate
      the DNA microarray analysis. The combined data demonstrate that HLA-DOB levels
      are increased by CIITA, and that this difference has an impact on the overall
      level of HLA-DO expression. Additionally, unlike the classical MHC class II
      genes, HLA-DOB expression was present in the absence of CIITA, indicating that
      additional factors mediate HLA-DOB expression in B cells.

PMID- 11823512
TI  - Nasal-associated lymphoid tissue is a mucosal inductive site for virus-specific
      humoral and cellular immune responses.
AB  - Peyer's patches are known as mucosal inductive sites for humoral and cellular
      immune responses in the gastrointestinal tract. In contrast, functionally
      equivalent structures in the respiratory tract remain elusive. It has been
      suggested that nasal-associated lymphoid tissue (NALT) might serve as a mucosal
      inductive site in the upper respiratory tract. However, typical signs of mucosal
      inductive sites like development of germinal center reactions after Ag
      stimulation and isotype switching of naive B cells to IgA production have not
      been directly demonstrated. Moreover, it is not known whether CTL can be
      generated in NALT. To address these issues, NALT was structurally and
      functionally analyzed using a model of intranasal infection of C3H mice with
      reovirus. FACS and histological analyses revealed development of germinal centers
      in NALT in parallel with generation and expansion of IgA(+) and IgG2a(+) B cells
      after intranasal reovirus infection. Reovirus-specific IgA was produced in both
      the upper respiratory and the gastrointestinal tract, whereas production of
      reovirus-specific IgG2a was restricted to NALT, submandibular, and mesenteric
      lymph nodes. Moreover, virus-specific CTL were detected in NALT. Limiting
      dilution analysis showed a 5- to 6-fold higher precursor CTL frequency in NALT
      compared with a cervical lymph node. Together these data provide direct evidence
      that NALT is a mucosal inductive site for humoral and cellular immune responses
      in the upper respiratory tract.

PMID- 11823513
TI  - Impaired resistance and enhanced pathology during infection with a noninvasive,
      attaching-effacing enteric bacterial pathogen, Citrobacter rodentium, in mice
      lacking IL-12 or IFN-gamma.
AB  - Mice infected with Citrobacter rodentium represent an excellent model in which to
      examine immune defenses against an attaching-effacing enteric bacterial pathogen.
      Colonic tissue from mice infected with C. rodentium harbors increased transcripts
      for IL-12 and IFN-gamma and displays mucosal pathology compared with uninfected
      controls. In this study, the role of IL-12 and IFN-gamma in host defense and
      mucosal injury during C. rodentium infection was examined using gene knockout
      mice. IL-12p40(-/-) and IFN-gamma(-/-) mice were significantly more susceptible
      to mucosal and gut-derived systemic C. rodentium infection. In particular, a
      proportion of IL-12p40(-/-) mice died during infection. Analysis of the gut
      mucosa of IL-12p40(-/-) mice revealed an influx of CD4(+) T cells and a local IFN
      gamma response. Infected IL-12p40(-/-) and IFN-gamma(-/-) mice also mounted anti
      Citrobacter serum and gut-associated IgA responses and strongly expressed
      inducible NO synthase (iNOS) in mucosal tissue, despite diminished serum
      nitrite/nitrate levels. However, iNOS does not detectably contribute to host
      defense against C. rodentium, as iNOS(-/-) mice were not more susceptible to
      infection. However, C57BL/6 mice infected with C. rodentium up-regulated
      expression of the mouse beta-defensin (mBD)-1 and mBD-3 in colonic tissue. In
      contrast, expression of mBD-3, but not mBD-1, was significantly attenuated during
      infection of IL-12- and IFN-gamma-deficient mice, suggesting mBD-3 may contribute
      to host defense. These studies are among the first to examine mechanisms of host
      resistance to an attaching-effacing pathogen and show an important role for IL-12
      and IFN-gamma in limiting bacterial infection of the colonic epithelium.

PMID- 11823514
TI  - Role of galectin-3 as an adhesion molecule for neutrophil extravasation during
      streptococcal pneumonia.
AB  - Recruitment of neutrophils from blood vessels to sites of infection represents
      one of the most important elements of innate immunity. Movement of neutrophils
      across blood vessel walls to the site of infection first requires that the
      migrating cells firmly attach to the endothelial wall. Generally, neutrophil
      extravasation is mediated at least in part by two classes of adhesion molecules,
      beta(2) integrins and selectins. However, in the case of streptococcal pneumonia,
      recent studies have revealed that a significant proportion of neutrophil
      diapedesis is not mediated by the beta(2) integrin/selectin paradigm. Galectin-3
      is a beta-galactoside-binding lectin implicated in inflammatory responses as well
      as in cell adhesion. Using an in vivo streptococcal pneumonia mouse model, we
      found that accumulation of galectin-3 in the alveolar space of streptococcus
      infected lungs correlates closely with the onset of neutrophil extravasation.
      Furthermore, immunohistological analysis of infected lung tissue revealed the
      presence of galectin-3 in the lung tissue areas composed of epithelial and
      endothelial cell layers as well as of interstitial spaces. In vitro, galectin-3
      was able to promote neutrophil adhesion to endothelial cells. Promotion of
      neutrophil adhesion by galectin-3 appeared to result from direct cross-linking of
      neutrophils to the endothelium and was dependent on galectin-3 oligomerization.
      Together, these results suggest that galectin-3 acts as an adhesion molecule that
      can mediate neutrophil adhesion to endothelial cells. However, accumulation of
      galectin-3 in lung was not observed during neutrophil emigration into alveoli
      induced by Escherichia coli infection, where the majority of neutrophil
      emigration is known to be beta(2) integrin dependent. Thus, based on our results,
      we propose that galectin-3 plays a role in beta(2) integrin-independent
      neutrophil extravasation, which occurs during alveolar infection with
      Streptococcus pneumoniae.

PMID- 11823515
TI  - Innate direct anticancer effector function of human immature dendritic cells. I.
      Involvement of an apoptosis-inducing pathway.
AB  - Dendritic cells (DCs) mediate cross-priming of tumor-specific T cells by
      acquiring tumor Ags from dead cancer cells. The process of cross-priming would be
      most economical and efficient if DCs also induce death of cancer cells. In this
      study, we demonstrate that normal human in vitro generated immature DCs
      consistently and efficiently induce apoptosis in cancer cell lines, freshly
      isolated noncultured cancer cells, and normal proliferating endothelial cells,
      but not in most normal cells. In addition, in vivo generated noncultured
      peripheral blood immature DCs mediate similar tumoricidal activity as their in
      vitro counterpart, indicating that this DC activity might be biologically
      relevant. In contrast to immature DCs, freshly isolated monocytes (myeloid DC
      precursors) and in vitro generated mature DCs are not cytotoxic or are less
      cytotoxic, respectively, suggesting that DC-mediated killing of cancer cells is
      developmentally regulated. Comparable cytotoxic activity is mediated by untreated
      DCs, paraformaldehyde-fixed DCs, and soluble products of DCs, and is destructible
      by proteases, indicating that both cell membrane-bound and secreted proteins
      mediate this DC function. Overall, our data demonstrate that human immature DCs
      are capable of inducing apoptosis in cancer cells and thus to both directly
      mediate anticancer activity and initiate processing of cellular tumor Ags.

PMID- 11823517
TI  - Deficiency in the anti-apoptotic protein A1-a results in a diminished acute
      inflammatory response.
AB  - A1 is an anti-apoptotic member of the Bcl-2 family that is up-regulated in
      inflammatory myeloid cells. In the present study, we investigated the role of A1
      in the maintenance of acute inflammation in mice. Mice possess three genes
      encoding highly related isoforms of A1. A1-a isoform mRNA was minimally expressed
      in resident peritoneal macrophages, but was present at a 300-fold higher level in
      inflammatory macrophages elicited by i.p. infection with Toxoplasma gondii. In
      comparison, A1-b and A1-d levels were 3- and 10-fold higher, respectively.
      Peritoneal leukocytosis was decreased in infected A1-a-deficient mice compared
      with wild-type, and this reduction was associated with a small but reproducible
      enhancement of survival. These effects could not be explained by an alteration in
      peritoneal parasite load, nor by increased apoptosis of infected inflammatory
      cells, which were protected from cell death by an A1-a-independent mechanism.
      Increased apoptosis in inflammatory neutrophils was observed sporadically in A1-a
      deficient mice. Regulation of apoptosis by A1-a may be an important
      proinflammatory event in acute host responses.

PMID- 11823516
TI  - Innate direct anticancer effector function of human immature dendritic cells. II.
      Role of TNF, lymphotoxin-alpha(1)beta(2), Fas ligand, and TNF-related apoptosis
      inducing ligand.
AB  - Our recent studies have demonstrated that human immature dendritic cells (DCs)
      are able to directly and effectively mediate apoptotic killing against a wide
      array of cultured and freshly-isolated cancer cells without harming normal cells.
      In the present study, we demonstrate that this tumoricidal activity is mediated
      by multiple cytotoxic TNF family ligands. We determine that human immature DCs
      express on their cell surface four different cytotoxic TNF family ligands: TNF,
      lymphotoxin-alpha(1)beta(2), Fas ligand, and TNF-related apoptosis inducing
      ligand; while cancer cells express the corresponding death receptors. Disruptions
      of interactions between the four ligands expressed on DCs and corresponding death
      signaling receptors expressed on cancer cells using specific Abs or R:Fc fusion
      proteins block the cytotoxic activity of DCs directed against cancer cells. The
      novel findings suggest that DC killing of cancer cells is mediated by the
      concerted engagement of four TNF family ligands of DCs with corresponding death
      receptors of cancer cells. Overall, our data demonstrate that DCs are fully
      equipped for an efficient direct apoptotic killing of cancer cells and suggest
      that this mechanism may play a critical role in both afferent and efferent anti
      tumor immunity.

PMID- 11823518
TI  - Recombinant canarypox vaccine-elicited CTL specific for dominant and subdominant
      simian immunodeficiency virus epitopes in rhesus monkeys.
AB  - Since virus-specific CTL play a central role in containing HIV replication, a
      candidate AIDS vaccine should generate virus-specific CTL responses. In this
      study, the ability of a recombinant canarypox virus expressing SIV Gag-Pol-Env
      (ALVAC/SIV gag-pol-env) was assessed for its ability to elicit both dominant and
      subdominant epitope-specific CTL responses in rhesus monkeys. Following a series
      of five immunizations, memory CTL responses specific for a dominant Gag epitope
      could be demonstrated in the peripheral blood of vaccinated monkeys. Memory CTL
      responses to a subdominant Pol epitope were undetectable in these animals.
      Following challenge with SIVmac251, the experimentally vaccinated animals
      developed high frequency CTL responses specific for the dominant Gag epitope that
      emerged in temporal association with the early containment of viral replication.
      Interestingly, the experimentally vaccinated, but not the control vaccinated
      animals, developed CTL responses to the subdominant Pol epitope that were
      detectable only after containment of early viremia. Thus, recombinant canarypox
      vaccination elicited low frequency, but durable memory CTL populations. The
      temporal association of the emergence of the dominant epitope-specific response
      with early viral containment following challenge suggests that this immune
      response played a role in the accelerated clearing of early viremia in these
      animals. The later emerging CTL response specific for the subdominant epitope may
      contribute to the control of viral replication in the setting of chronic
      infection.

PMID- 11823519
TI  - Efficient in vivo presentation of Listeria monocytogenes- derived CD4 and CD8 T
      cell epitopes in the absence of IFN-gamma.
AB  - IFN-gamma is an essential component of the early Listeria monocytogenes-specific
      immune response, and is also an important regulator of Ag processing and
      presentation. Ag presentation is required for the induction and also the effector
      function of antimicrobial T cells. To evaluate the effect of IFN-gamma on
      bacterial Ag presentation in vivo, macrophages and dendritic cells were separated
      from L. monocytogenes-infected tissues and analyzed with peptide-specific CD4 and
      CD8 T cell lines in a sensitive ELISPOT-based ex vivo Ag presentation assay. The
      comparison of professional APCs isolated from infected IFN-gamma-deficient and
      wild-type mice revealed different peptide presentation patterns of L.
      monocytogenes-derived CD8 T cell epitopes, while the presentation pattern of CD4
      T cell epitopes remained unchanged. The further in vitro analysis of the
      generation of CD8 T cell epitopes revealed a peptide-specific effect of IFN-gamma
      on MHC class I-restricted Ag presentation. These results show that despite this
      modulation of the Ag presentation pattern of CD8 T cell epitopes, IFN-gamma is
      not generally required for the MHC class I- and MHC class II-restricted
      presentation of L. monocytogenes-derived antigenic peptides by professional APCs
      in vivo.

PMID- 11823520
TI  - Induction of neutrophil apoptosis by the Pseudomonas aeruginosa exotoxin
      pyocyanin: a potential mechanism of persistent infection.
AB  - Pseudomonas aeruginosa colonizes and infects human tissues, although the
      mechanisms by which the organism evades the normal, predominantly neutrophilic,
      host defenses are unclear. Phenazine products of P. aeruginosa can induce death
      in Caenorhabditis elegans. We hypothesized that phenazines induce death of human
      neutrophils, and thus impair neutrophil-mediated bacterial killing. We
      investigated the effects of two phenazines, pyocyanin and 1-hydroxyphenazine,
      upon apoptosis of neutrophils in vitro. Pyocyanin induced a concentration- and
      time-dependent acceleration of neutrophil apoptosis, with 50 microM pyocyanin
      causing a 10-fold induction of apoptosis at 5 h (p < 0.001), a concentration that
      has been documented in sputum from patients colonized with P. aeruginosa. 1
      hydroxyphenazine was without effect. In contrast to its rapid induction of
      neutrophil apoptosis, pyocyanin did not induce significant apoptosis of monocyte
      derived macrophages or airway epithelial cells at time points up to 24 h.
      Comparison of wild-type and phenazine-deleted strains of P. aeruginosa showed a
      highly significant reduction in neutrophil killing by the phenazine-deleted
      strain. In clinical isolates of P. aeruginosa pyocyanin production was associated
      with a proapoptotic effect upon neutrophils in culture. Pyocyanin-induced
      neutrophil apoptosis was not delayed either by treatment with LPS, a powerfully
      antiapoptotic bacterial product, or in neutrophils from cystic fibrosis patients.
      Pyocyanin-induced apoptosis was associated with rapid and sustained generation of
      reactive oxygen intermediates and subsequent reduction of intracellular cAMP.
      Treatment of neutrophils with either antioxidants or synthetic cAMP analogues
      significantly abrogated pyocyanin-induced apoptosis. We conclude that pyocyanin
      induced neutrophil apoptosis may be a clinically important mechanism of
      persistence of P. aeruginosa in human tissue.

PMID- 11823521
TI  - Cell-mediated immunity induced by recombinant Mycobacterium bovis Bacille
      Calmette-Guerin strains against an intracellular bacterial pathogen: importance
      of antigen secretion or membrane-targeted antigen display as lipoprotein for
      vaccine efficacy.
AB  - Live recombinant vaccines expressing defined pathogen-derived Ags represent
      powerful candidates for future vaccination strategies. In this study, we report
      on the differential induction of protective cell-mediated immunity elicited by
      different recombinant Mycobacterium bovis Bacille Calmette-Guerin (BCG) strains
      displaying p60 Ag of Listeria monocytogenes in secreted, cytosolic, or membrane
      attached form for T cell recognition. Anti-listerial protection evoked by the
      membrane-linked p60 lipoprotein of rBCG Mp60 and that of the p60 derivative
      secreted by rBCG Sp60-40 were nearly equal, whereas cytosolic p60 displayed by
      rBCG Np60 failed to protect mice from listeriosis. In vivo depletion of CD4 or
      CD8 T cell subpopulations in rBCG Mp60-vaccinated mice before listerial challenge
      revealed interactions of both T cell subsets in anti-listerial protection. In
      rBCG Sp60-40-vaccinated animals, CD4 T cells predominantly contributed to anti
      listerial control as shown by the failure of anti-CD8 mAb treatment to impair the
      outcome of listeriosis in rBCG Sp60-40-vaccinated mice after L. monocytogenes
      challenge. Hence, differential Ag display by rBCG influences cell-mediated
      immunity, which in turn may impact vaccine efficacy due to the different
      requirements of CD4 or CD8 T cells for pathogen elimination.

PMID- 11823522
TI  - Oral DNA vaccination in utero induces mucosal immunity and immune memory in the
      neonate.
AB  - Infectious diseases are responsible for a significant number of deaths during the
      first weeks of life. Some of the salient pathogens include HSV, HIV, hepatitis B
      virus, group B streptococcus, Haemophilus sp., and Chlamydia sp. The vertical
      transmission of many of these pathogens significantly increases the risk of
      neonatal infection. We recently reported that oral DNA immunization in utero
      induced high serum Ab titers and cell-mediated immunity in fetal lambs. In this
      study, we demonstrate immune memory and mucosal immunity in newborn lambs
      following oral DNA immunization of the fetus. A single oral exposure in utero to
      plasmid DNA encoding a truncated form of glycoprotein D of bovine herpesvirus-1
      induced detectable immune responses in 80% (12 of 15) of newborn lambs. There was
      no evidence for the induction of immune tolerance in nonresponding lambs.
      Responding lambs displayed both systemic and mucosal immune responses and reduced
      virus shedding following intranasal challenge. Furthermore, strong anamnestic
      responses were evident for at least 3 mo after birth. The efficacy of in utero
      oral DNA immunization was further demonstrated with the hepatitis B surface Ag,
      and protective serum Ab titers occurred in 75% of immunized lambs. Thus, the
      present investigation confirms that oral DNA immunization in utero can induce
      both mucosal and systemic immune responses in the neonate and that this immunity
      has the potential to prevent vertical disease transmission.

PMID- 11823523
TI  - Streptococcus pneumoniae evades complement attack and opsonophagocytosis by
      expressing the pspC locus-encoded Hic protein that binds to short consensus
      repeats 8-11 of factor H.
AB  - Streptococcus pneumoniae is an important cause of upper and lower respiratory
      tract infections, meningitis, peritonitis, bacterial arthritis, and sepsis. Here
      we have studied a novel immune evasion mechanism of serotype 3 pneumococci, which
      are particularly resistant to phagocytosis. On their surfaces the bacteria
      express the factor H-binding inhibitor of complement (Hic), a protein of the
      pneumococcal surface protein C family. Using radioligand binding, microtiter
      plate assays, surface plasmon resonance analysis, and recombinant constructs of
      factor H, we located the binding site of Hic to short consensus repeats (SCRs) 8
      11 in the middle part of factor H. This represents a novel microbial interaction
      region on factor H. The only other ligand known so far for SCRs 8-11 of factor H
      is C-reactive protein (CRP), an acute phase protein that binds to the
      pneumococcal C-polysaccharide. The binding sites of Hic and CRP within the SCR8
      11 region were different, however, because CRP did not inhibit the binding of Hic
      and required calcium for binding. Binding of factor H to Hic-expressing
      pneumococci promoted factor I-mediated cleavage of C3b and restricted
      phagocytosis of pneumococci. Thus, virulent pneumococci avoid complement attack
      and opsonophagocytosis by recruiting functionally active factor H with the Hic
      surface protein. Hic binds to a previously unrecognized microbial interaction
      site in the middle part of factor H.

PMID- 11823524
TI  - IL-4 up-regulates the expression of tissue inhibitor of metalloproteinase-2 in
      dermal fibroblasts via the p38 mitogen-activated protein kinase dependent
      pathway.
AB  - Tissue inhibitor of metalloproteinase-2 (TIMP-2) is a potent inhibitor of
      activated matrix metalloproteinases such as gelatinase and collagenase, and thus
      helps to control extracellular matrix metabolism and deposition by connective
      tissue cells. We examined the responsiveness of the expression of TIMP-2 to
      various cytokines in dermal fibroblasts and studied the regulatory and signaling
      mechanisms of the response. TIMP-2 protein and mRNA expression was induced by IL
      4 in a dose- and time-dependent manner, but not by TGF-beta, oncostatin M, or IL
      6. IL-4 induction of TIMP-2 expression was dependent upon transcription. The p38
      mitogen-activated protein kinase (MAPK) inhibitors SB202190 and SB203580
      suppressed IL-4-induced TIMP-2 expression, suggesting the involvement of p38 MAP
      kinase in the signaling of IL-4 leading to TIMP-2 expression. Immunoblotting
      analysis using a specific Ab against phosphorylated p38 MAP kinase
      (Thr(180)/Tyr(182)) showed that IL-4 induced phosphorylation of p38 MAP kinase in
      human dermal fibroblasts. Furthermore, the p38 MAP kinase assay showed that IL-4
      induces p38 MAPK activation in human dermal fibroblasts. The expression of the
      dominant-negative mutant p38 MAPK represses the IL-4-induced TIMP-2 expression in
      human dermal fibroblasts. Thus, IL-4 can potentially alter the dermal matrix
      metabolism by regulating TIMP-2.

PMID- 11823525
TI  - Functional IL-10 deficiency in the lung of cystic fibrosis (cftr(-/-)) and IL-10
      knockout mice causes increased expression and function of B7 costimulatory
      molecules on alveolar macrophages.
AB  - Alveolar macrophages are poor APCs that only minimally express B7 costimulatory
      molecules. Because our previous data suggest that bronchial epithelial cells
      constitutively secrete IL-10, and IL-10 inhibits B7 expression in vitro, we
      hypothesized that this IL-10 is responsible for suppressing B7 expression on
      macrophages that enter the airways. Furthermore, because we have shown that
      cystic fibrosis (CF) lungs are deficient in IL-10, we hypothesized that
      bronchoalveolar macrophages (BALMs) from cystic fibrosis transmembrane
      conductance regulator (CFTR)(-/-) as well as IL-10(-/-) mice might express
      increased B7. Immunofluorescence for B7 was positive on BALMs from CF patients
      and CFTR(-/-) and IL-10(-/-) mice, but was negative on controls. FACS showed that
      63.9% of BALMs from IL-10(-/-) mice were B7-1 positive, as were 67.4% of BALMs
      from CFTR(-/-) mice, whereas <7% of BALMs from wild-type controls were positive.
      Using BALMs to costimulate splenic T cells with anti-CD3 as a mitogen showed 9202
      +/- 2107 cpm [(3)H]thymidine incorporation for BALMs from IL-10(-/-) mice and
      4082 +/- 1036 cpm for BALMs from CFTR(-/-) mice, but <200 cpm with BALMs from
      either type of +/+ mouse. Treatment of CFTR(-/-) mice with recombinant mouse IL
      10 reduced the B7 expression and costimulatory activity of the BALMs. These data
      suggest that the IL-10 secreted in the healthy lung may be responsible for the
      absence of B7 and poor costimulatory activity of BALMs and that reductions of
      pulmonary IL-10 in CF may enhance B7 expression and local immune responses.

PMID- 11823526
TI  - Eotaxin-2 generation is differentially regulated by lipopolysaccharide and IL-4
      in monocytes and macrophages.
AB  - The eotaxins are a family of CC chemokines that coordinate the recruitment of
      inflammatory cells, in particular eosinophils, to sites of allergic inflammation.
      The cDNA for eotaxin-2 (CC chemokine ligand 24) was originally isolated from an
      activated monocyte library. In this study, we show for the first time that
      peripheral blood monocytes generate bioactive eotaxin-2 protein constitutively.
      Eotaxin-2 production was significantly up-regulated when monocytes were
      stimulated with the proinflammatory cytokine IL-1beta and the microbial stimuli,
      LPS and zymosan. In contrast, the Th2 cytokines, IL-4 and IL-13, and the
      proinflammatory cytokine, TNF-alpha, acting alone or in combination, did not
      enhance the generation of eotaxin-2 by monocytes. Indeed, IL-4 suppressed the
      generation of eotaxin-2 by LPS-stimulated monocytes. Although other chemokines,
      including macrophage-inflammatory protein-1alpha, monocyte chemoattractant
      protein-1, macrophage-derived chemokine, and IL-8 were generated by monocytes,
      eotaxin-1 (CC chemokine ligand 11) could not be detected in the supernatants of
      monocytes cultured in the presence or absence of any of the stimuli used in the
      above experiments. Furthermore, human dermal fibroblasts that produce eotaxin-1
      did not generate eotaxin-2 under basal conditions or when stimulated with
      specific factors, including IL-4, IL-13, TNF-alpha, and LPS. When monocytes were
      differentiated into macrophages, their constitutive generation of eotaxin-2 was
      suppressed. Moreover, IL-4, but not LPS, up-regulated the production of eotaxin-2
      by macrophages. Taken as a whole, these results support a role for macrophage
      derived eotaxin-2 in adaptive immunity, with a Th2 bias. In contrast, a role for
      monocyte-derived eotaxin-2 is implicated in innate immunity.

PMID- 11823527
TI  - Expression and function of the C5a receptor in rat alveolar epithelial cells.
AB  - Although alveolar epithelial cells (AEC) form an important barrier for host
      defenses in the lung, there is limited information about ways in which AEC can
      directly participate in the lung inflammatory response. In the current studies,
      primary cultures of rat AEC (RAEC) have been shown to specifically bind
      recombinant rat C5a at high affinity and in a saturable manner. This binding was
      enhanced in a time-dependent manner by pre-exposure of RAEC to LPS, IL-6, or TNF
      alpha, the increased binding of C5a being associated with increased levels of
      mRNA for the C5a receptor (C5aR). Exposure of RAEC to C5a also caused increased
      expression of mRNA for C5aR. As compared with exposure of RAEC to LPS or to C5a
      alone, exposure to the combination caused enhanced production of TNF-alpha,
      macrophage inflammatory protein-2, and cytokine-induced neutrophil
      chemoattractant-1, as well as increased intracellular levels of IL-1beta. These
      data indicate that RAEC, when activated, have enhanced binding of C5a in
      association with increased mRNA for C5aR. The functional outcome is enhanced
      release of proinflammatory mediators. These data underscore the phlogistic
      potential of RAEC and the ability of C5a to enhance the phlogistic responses of
      RAEC.

PMID- 11823528
TI  - Inflammatory response and glutathione peroxidase in a model of stroke.
AB  - Stroke is one of the leading causes of death in major industrial countries. Many
      factors contribute to the cellular damage resulting from ischemia/reperfusion
      (I/R). Experimental data indicate an important role for oxidative stress and the
      inflammatory cascade during I/R. We are testing the hypothesis that the mechanism
      of protection against I/R damage observed in transgenic mice overexpressing human
      antioxidant enzymes (particularly intracellular glutathione peroxidase) involves
      the modulation of inflammatory response as well as reduced sensitivity of neurons
      to cytotoxic cytokines. Transgenic animals show significant reduction of
      expression of chemokines, IL-6, and cell death-inducing ligands as well as
      corresponding receptors in a focal cerebral I/R model. Reduction of DNA binding
      activity of consensus and potential AP-1 binding sites in mouse Fas ligand
      promoter sequence was observed in nuclear extracts from transgenic mice
      overexpressing intracellular glutathione peroxidase compared with normal animals
      following I/R. This effect was accompanied by modulation of the c-Jun N-terminal
      kinase/stress-activated protein kinase pathway. Cultured primary neurons from the
      transgenic mice demonstrated protection against hypoxia/reoxygenation injury as
      well as cytotoxicity after TNF-alpha and Fas ligand treatment. These results
      indicate that glutathione peroxidase-sensitive reactive oxygen species play an
      important role in regulation of cell death during cerebral I/R by modulating
      intrinsic neuronal sensitivity as well as brain inflammatory reactions.

PMID- 11823529
TI  - The role of E-selectin, P-selectin, and very late activation antigen-4 in T
      lymphocyte migration to dermal inflammation.
AB  - T lymphocyte infiltration into inflamed tissues is thought to involve lymphocyte
      rolling on vascular endothelial cells. Because both selectin and alpha(4)
      integrin adhesion molecules can mediate leukocyte rolling, the contribution of
      these receptors to lymphocyte migration to inflammation was examined. The
      recruitment of (111)In-labeled spleen T cells to intradermal sites injected with
      IFN-gamma, TNF-alpha, LPS, poly inosine-cytosine, and Con A was measured in the
      rat, and the effect of blocking mAbs to E-selectin, P-selectin, very late
      activation Ag-4 (VLA-4), and LFA-1 was determined on this T cell migration in
      vivo. Anti-E-selectin and anti-P-selectin mAbs each inhibited 10-40 and 20-48%,
      respectively, of the T lymphocyte migration to the inflammatory sites, depending
      on the stimulus. Blocking VLA-4 inhibited 50% of the migration to all of the
      lesions except Con A. Treatment with both anti-VLA-4 and anti-E-selectin mAbs
      inhibited up to 85% of the lymphocyte accumulation, while P-selectin and VLA-4
      blockade in combination was not more effective than VLA-4 blockade alone in TNF
      alpha, IFN-gamma, LPS, and poly inosine-cytosine lesions. Inhibiting E-selectin,
      P-selectin, and VLA-4 together nearly abolished lymphocyte migration to all
      inflammatory sites. Anti-LFA-1 mAb strongly inhibited lymphocyte accumulation by
      itself, and this inhibition was not significantly further reduced by E- or P
      selectin blockade. Thus, T cell migration to dermal inflammation is dependent on
      E-selectin, P-selectin, and VLA-4, likely because these three receptors are
      required for rolling of memory T lymphocytes, but VLA-4 and E-selectin are
      especially important for lymphocyte infiltration in these tissues.

PMID- 11823530
TI  - Molecular mechanisms involved in lymphocyte recruitment in inflamed brain
      microvessels: critical roles for P-selectin glycoprotein ligand-1 and
      heterotrimeric G(i)-linked receptors.
AB  - Lymphocyte recruitment into the brain is a critical event in the pathogenesis of
      multiple sclerosis and experimental autoimmune encephalomyelitis. We developed a
      novel intravital microscopy model to directly analyze through the skull the
      interactions between lymphocytes and the endothelium in cerebral venules of mice.
      No adhesive interactions were observed between lymphocytes and the nonactivated
      endothelium in the cerebral microcirculation. When brain venules were activated
      by pretreating mice with TNF-alpha or LPS, proteolipid protein 139-151
      autoreactive T lymphocytes rolled and arrested; notably, only a few peripheral
      lymph node cells rolled and firmly adhered. Abs anti-P-selectin glycoprotein
      ligand-1 and anti-E- and P-selectin blocked tethering and rolling of autoreactive
      lymphocytes, suggesting that P-selectin glycoprotein ligand-1/endothelial
      selectins are critical in the recruitment of lymphocytes in inflamed brain
      venules. E- and P-selectin were expressed on cerebral vessels upon in vivo
      activation and had a patchy distribution during the preclinical phase of active
      and passive experimental autoimmune encephalomyelitis. LFA-1/ICAM-1 and alpha(4)
      integrins/VCAM-1 supported rolling, but were not relevant to rolling velocity.
      Firm arrest was mainly mediated by LFA-1 and ICAM-1. Pretreatment of autoreactive
      lymphocytes with pertussis toxin blocked integrin-dependent arrest, implicating a
      requirement for G(i) protein-dependent signaling in vessels from nonlymphoid
      districts. In conclusion, our data unveils the molecular mechanisms controlling
      the recruitment of autoreactive lymphocytes in inflamed cerebral vessels and
      suggest new insights into the pathogenesis of autoimmune inflammatory diseases of
      the CNS.

PMID- 11823531
TI  - Recruitment of MHC class I molecules by tapasin into the transporter associated
      with antigen processing-associated complex is essential for optimal peptide
      loading.
AB  - The ER protein tapasin (Tpn) forms a bridge between MHC class I H chain
      (HC)/beta(2)-microglobulin and the TAP peptide transporter. The function of this
      TAP-associated complex was unclear because it was reported that soluble Tpn that
      has lost TAP interaction would be fully competent in terms of peptide loading and
      Ag presentation. We found, however, that only wild-type human Tpn (hTpn), but not
      three soluble hTpn variants, a transmembrane domain point mutant of hTpn (L410-
      >F), wild-type mouse Tpn, nor a mouse-human Tpn hybrid, fully up-regulated
      peptide-dependent Bw4 epitopes when expressed in Tpn-deficient.220.B*4402 cells.
      Consistent with suboptimal peptide loading, the t(1/2) of class I molecules was
      considerably reduced in the presence of soluble hTpn, hTpn-L410F, and murine Tpn.
      Furthermore, eluted peptide spectra and the class I-mediated inhibition of NK
      clones showed distinct differences to the hTpn transfectant. Only wild-type hTpn
      efficiently recruited HC and calreticulin (Crt) into complexes with TAP and
      endoplasmic reticulum p57 (ERp57). The L410F mutant was defective in TAP
      association, but bound to class I molecules, Crt, and ERp57. Mouse Tpn associated
      with human TAP and ERp57 on the one hand, and with HC and Crt on the other, but
      failed to recruit normal amounts of HLA class I molecules into the TAP complex.
      We conclude that the loading with peptides conferring high stability requires the
      Tpn-mediated introduction of HC into the TAP complex, whereas the mere
      interaction with Tpn is not sufficient.

PMID- 11823532
TI  - Biological activities of ecalectin: a novel eosinophil-activating factor.
AB  - Ecalectin, produced by Ag-stimulated T lymphocytes, is a potent eosinophil
      specific chemoattractant in vitro as well as in vivo and thus is implicated in
      allergic responses. Ecalectin differs structurally from other known eosinophil
      chemoattractants (ECAs); ecalectin belongs to the galectin family defined by
      their affinity for beta-galactosides and by their conserved carbohydrate
      recognition domains. These characteristic features suggest that ecalectin has
      unique activities associated with allergic inflammation besides ECA activity.
      Conversely, ecalectin may mediate ECA activity by binding to a receptor of a
      known ECA via affinity for the beta-galactosides present on this receptor. In
      this study, we have tested whether ecalectin mediates ECA activity by binding to
      a receptor of a known ECA, and we have assessed its effects on eosinophils.
      Ecalectin did not mediate ECA activity by binding to the IL-5R or to CCR3. Also,
      the ECA activity of ecalectin was mainly chemokinetic. In addition, ecalectin
      induced concentration-dependent eosinophil aggregation, a marker for eosinophil
      activation. Ecalectin induced concentration-dependent superoxide production from
      eosinophils but did not induce degranulation; usually these two events are
      coupled in eosinophil activation. Moreover, ecalectin directly prolonged
      eosinophil survival in vitro and did not trigger eosinophils to secrete cytokines
      that prolong eosinophil survival. These results demonstrate that ecalectin has
      several unique effects on eosinophils. Therefore, we conclude that ecalectin is a
      novel eosinophil-activating factor. Presumably, these effects allow ecalectin to
      play a distinctive role in allergic inflammation.

PMID- 11823533
TI  - Lipopolysaccharide induces rapid production of IL-10 by monocytes in the presence
      of apoptotic neutrophils.
AB  - There is growing evidence that apoptotic neutrophils have an active role to play
      in the regulation and resolution of inflammation following phagocytosis by
      macrophages and dendritic cells. However, their influence on activated blood
      monocytes, freshly recruited to sites of inflammation, has not been defined. In
      this work, we examined the effect of apoptotic neutrophils on cytokine production
      by LPS-activated monocytes. Monocytes stimulated with LPS in the presence of
      apoptotic neutrophils for 18 h elicited an immunosuppressive cytokine response,
      with enhanced IL-10 and TGF-beta production and only minimal TNF-alpha and IL
      1beta cytokine production. Time-kinetic studies demonstrated that IL-10
      production was markedly accelerated in the presence of apoptotic neutrophils,
      whereas there was a sustained reduction in the production of TNF-alpha and IL
      1beta. This suppression of proinflammatory production was not reversible by
      depletion of IL-10 or TGF-beta or by addition of exogenous IFN-gamma. It was
      demonstrated, using Transwell experiments, that monocyte-apoptotic cell contact
      was required for induction of the immunosuppressive monocyte response. The
      response of monocytes contrasted with that of human monocyte-derived macrophages
      in which there was a reduction in IL-10 production. We conclude from these data
      that interaction between activated monocytes and apoptotic neutrophils creates a
      unique response, which changes an activated monocyte from being a promoter of the
      inflammatory cascade into a cell primed to deactivate itself and other cells.

PMID- 11823534
TI  - Lyn tyrosine kinase is important for IL-5-stimulated eosinophil differentiation.
AB  - IL-5 plays a pivotal role in growth and differentiation of eosinophils. The
      signal transduction mechanism of IL-5Ralpha is largely unknown. We have
      demonstrated that IL-5 induces tyrosine phosphorylation of IL-5Ralpha in
      eosinophils. To identify IL-5Ralpha-associated tyrosine kinases, we have examined
      the expression of Src family tyrosine kinases in eosinophils. Among the Src
      family members, Lyn, Hck, Fgr, and Lck are present in eosinophils, and, among
      these four kinases, only Lyn is associated with the IL-5Ralpha under basal
      conditions. We also confirm the association of Janus kinase (Jak)2 with IL
      5Ralpha. Lyn kinase phosphorylates both IL-5Ralpha and betacR in vitro. The
      importance of Lyn kinase for eosinophil differentiation was studied using
      antisense oligodeoxynucleotides. Lyn antisense oligodeoxynucleotide blocks
      eosinophil differentiation from stem cells in a dose-dependent manner. The Jak2
      inhibitor tyrphostin AG490 also inhibits eosinophil differentiation. The
      importance of Lyn for eosinophil differentiation was further studied using Lyn
      knockout mice. The IL-5-stimulated eosinophil differentiation from bone marrow
      cells is significantly inhibited in Lyn(-/-) mice as compared with that in
      control mice. We conclude that both Lyn and Jak2 play an essential role in IL
      5Ralpha signaling, leading to eosinophil differentiation. The effect of Lyn
      appears to be relatively specific for the eosinophilic lineage.

PMID- 11823535
TI  - Autocrine induction of the human pro-IL-1beta gene promoter by IL-1beta in
      monocytes.
AB  - IL-1beta is produced primarily by activated monocytes/macrophages. We report in
      this study that IL-1beta induces the human pro-IL-1beta (IL1B) gene promoter in
      human THP-1 monocytic cells. The -131 to +12 minimal IL1B promoter was induced by
      IL-1beta in a dose-dependent manner. The promoter possesses two important
      transcription factor binding motifs, one for an ETS family transcription factor
      Spi-1 (PU.1), and the other a binding site for NF-IL6 (CCAAT/enhancer binding
      protein beta). Autocrine promoter activity was completely inhibited by mutation
      of the Spi-1 site. Mutation of the NF-IL6 binding motif caused partial loss of
      activity. EMSAs using THP-1 cell nuclear extracts indicated that IL-1beta
      significantly induced Spi-1 binding to its target site within the IL1B promoter
      that was maximal at 1 h after stimulation, correlating with the kinetics of IL
      1beta induction. The importance of Spi-1 was supported by our observation that
      Spi-1-deficient EL4 thymocytes exhibited IL-1beta-induced activity only after
      transfection with a Spi-1 expression vector. Moreover, TNFR-associated factor 6
      also required Spi-1 to activate the promoter. Transfection studies using Spi-1
      mutant constructs showed that the TATA-binding protein binding and glutamine-rich
      domains of Spi-1 were important for IL-1beta induction, whereas LPS induction
      required the proline, glutamic acid, serine, and threonine-rich domain containing
      serine 148 as well as the TATA-binding protein and glutamine-rich domains. We
      conclude that the IL1B promoter is an IL-1beta-responsive sequence as a result of
      its ability to bind Spi-1 in response to IL-1beta.

PMID- 11823536
TI  - Tryptase inhibition blocks airway inflammation in a mouse asthma model.
AB  - Release of human lung mast cell tryptase may be important in the pathophysiology
      of asthma. We examined the effect of the reversible, nonelectrophilic tryptase
      inhibitor MOL 6131 on airway inflammation and hyper-reactivity in a murine model
      of asthma. MOL 6131 is a potent selective nonpeptide inhibitor of human lung mast
      cell tryptase based upon a beta-strand template (K(i) = 45 nM) that does not
      inhibit trypsin (K(i) = 1,061 nM), thrombin (K(i) = 23, 640 nM), or other serine
      proteases. BALB/c mice after i.p. OVA sensitization (day 0) were challenged
      intratracheally with OVA on days 8, 15, 18, and 21. MOL 6131, administered days
      18-21, blocked the airway inflammatory response to OVA assessed 24 h after the
      last OVA challenge on day 22; intranasal delivery (10 mg/kg) had a greater anti
      inflammatory effect than oral delivery (10 or 25 mg/kg) of MOL 6131. MOL 6131
      reduced total cells and eosinophils in bronchoalveolar lavage fluid, airway
      tissue eosinophilia, goblet cell hyperplasia, mucus secretion, and peribronchial
      edema and also inhibited the release of IL-4 and IL-13 in bronchoalveolar lavage
      fluid. However, tryptase inhibition did not alter airway hyper-reactivity to
      methacholine in vivo. These results support tryptase as a therapeutic target in
      asthma and indicate that selective tryptase inhibitors can reduce allergic airway
      inflammation.

PMID- 11823537
TI  - Functional genomic analysis of type II IL-1beta decoy receptor: potential for
      gene therapy in human arthritis and inflammation.
AB  - Gene expression arrays show that human epithelial cells and human arthritis
      affected cartilage lack detectable amounts of mRNA for IL-1 antagonizing
      molecules: IL-1Ra and IL-1RII, but constitutively express IL-1. Functional
      genomic analysis was performed by reconstituting human IL-1RII expression in
      various IL-1RII-deficient cell types to examine its antagonist role using gene
      therapy approaches. Adenovirus-expressing IL-1RII when transduced into human and
      bovine chondrocytes, human and rabbit synovial cells, human epithelial cells, and
      rodent fibroblasts expressed membrane IL-1RII and spontaneously released
      functional soluble IL-1RII. The IL-1RII(+) (but not IL-1RII(-)) cells were
      resistant to IL-1beta-induced, NO, PGE(2), IL-6, and IL-8 production or decreased
      proteoglycan synthesis. IL-1RII inhibited the function of IL-1 in chondrocytes
      and IL-1- and TNF-alpha-induced inflammatory mediators in human synovial and
      epithelial cells. IL-1RII(+) chondrocytes were more resistant to induction of NO
      and PGE(2) by IL-1beta compared with IL-1RII(-) cells incubated with a 10-fold
      (weight) excess of soluble type II IL-1R (sIL-1RII) protein. In cocultures, IL
      1RII(+) synovial cells released sIL-1RII, which in a paracrine fashion protected
      chondrocytes from the effects of IL-1beta. Furthermore, IL-1RII(+) (but not IL
      1RII(-)) chondrocytes when transplanted onto human osteoarthritis-affected
      cartilage in vitro, which showed spontaneous release of sIL-1RII for 20 days,
      inhibited the spontaneous production of NO and PGE(2) in cartilage in ex vivo. In
      summary, reconstitution of IL-1RII in IL-1RII(-) cells using gene therapy
      approaches significantly protects cells against the autocrine and paracrine
      effects of IL-1 at the signaling and transcriptional levels.

PMID- 11823538
TI  - G-CSF therapy of ongoing experimental allergic encephalomyelitis via chemokine-
      and cytokine-based immune deviation.
AB  - Converging evidence that G-CSF, the hemopoietic growth factor of the myeloid
      lineage, also exerts anti-inflammatory and pro-Th2 effects, prompted us to
      evaluate its direct therapeutic potential in autoimmune diseases. Here we report
      a novel activity of G-CSF in experimental allergic encephalomyelitis, a murine
      model for multiple sclerosis, driven by Th1-oriented autoaggressive cells. A
      short 7-day treatment with G-CSF, initiated at the onset of clinical signs,
      provided durable protection from experimental autoimmune encephalomyelitis. G-CSF
      treated mice displayed limited demyelination, reduced recruitment of T cells to
      the CNS, and very discrete autoimmune inflammation, as well as barely detectable
      CNS mRNA levels of cytokines and chemokines. In the periphery, G-CSF treatment
      triggered an imbalance in the production by macrophages as well as autoreactive
      splenocytes of macrophage inflammatory protein-1alpha and monocyte
      chemoattractant protein-1, the prototypical pro-Th1 and pro-Th2 CC chemokines,
      respectively. This chemokine imbalance was associated with an immune deviation of
      the autoreactive response, with reduced IFN-gamma and increased IL-4 and TGF
      beta1 levels. Moreover, G-CSF limited the production of TNF-alpha, a cytokine
      also associated with early CNS infiltration and neurological deficit. These
      findings support the potential application of G-CSF in the treatment of human
      autoimmune diseases such as multiple sclerosis, taking advantage of the wide
      clinical favorable experience with this molecule.

PMID- 11823539
TI  - Development of atopic dermatitis-like skin lesions in STAT6-deficient NC/Nga
      mice.
AB  - Atopic dermatitis (AD) is a pruritic inflammatory skin disease characterized by
      elevation of plasma levels of total IgE, infiltration of mast cells and
      eosinophils, and the expression of cytokines by Th2 T cells. However, the role of
      Th2 cells in the pathogenesis of AD is not fully understood. In this study we
      examined the NC/Nga (NC) mouse model of AD and established STAT6-deficient
      (SATA6(-/-)) NC mice to investigate the relevance of IL-4-mediated immune
      responses. Surprisingly, these mice elicited AD-like skin lesions at equivalent
      frequency and time of onset compared with normal NC littermates. Histological
      features of the lesion in STAT6(-/-) NC mice fulfilled the criteria for the
      pathogenesis of AD, although these mice fail to produce IgE and Th2 cytokines.
      The lymph nodes proximal to the regions of skin that developed lesions exhibited
      massive enlargement elicited by the accumulation of activated IFN-gamma-secreting
      T cells. Moreover, caspase I, IL-18, IL-12, and IFN-gamma are found to be highly
      expressed at the skin lesion, occurring simultaneously with elevation of eotaxin
      2 and CCR3 expression. Therefore, the Th2-mediated immune response is not
      necessary for the development of AD-like skin disease in NC mice. The skin
      microenvironment that favored IFN-gamma production tightly correlates with the
      skin disease in NC mice through the infiltration of eosinophils.

PMID- 11823540
TI  - Long-term survival of corneal allografts is dependent on intact CD1d-reactive NKT
      cells.
AB  - BALB/c mice that tolerate the allogeneic grafts develop allogeneic-specific
      anterior chamber-associated immune deviation. Because CD1d-reactive NKT cells are
      essential for anterior chamber-associated immune deviation, we postulated that
      the survival of C57BL/6 (B6) cornea graft in BALB/c mice was also dependent on
      CD1d-reactive NKT cells. The B6 corneal graft rejection rate in BALB/c vs
      Jalpha281 knockout (KO) mice, which lack NKT cells, was measured. While there
      were no difference in the early phase of rejection, the survival rates at 12 wk
      after grafting for BALB/c and Jalpha281 KO mice were 50 and 0%, respectively.
      Because anti-CD1d mAb abrogated the corneal graft survival in the wild-type mice
      we concluded that CD1d-reactive NKT cells were essential for graft survival.
      Moreover, allospecific T regulatory (Tr) cells correlated with acceptance of B6
      grafts in BALB/c mice, and the adoptive transfer of these allospecific Tr cells
      to Jalpha281 KO mice allowed a 50% survival rate of B6 cornea grafts. In
      conclusion, CD1d-reactive NKT cells are required for induction of allospecific Tr
      cells and are essential for survival of corneal allografts. Mechanisms that
      contribute to cornea graft acceptance may lead to new therapies for improvement
      in graft survival in high-risk corneas and other transplanted tissues and grafts.

PMID- 11823541
TI  - Human IgG monoclonal anti-alpha(IIb)beta(3)-binding fragments derived from
      immunized donors using phage display.
AB  - Previous studies of the immune response in polytransfused Glanzmann
      thrombasthenia (GT) patients and in autoimmune thrombocytopenic purpura (AITP)
      have relied on serum analysis and have shown the frequent development of Abs
      directed against the alpha(IIb)beta(3) integrin. However, little is known about
      the molecular diversity of the humoral immune response to alpha(IIb)beta(3) due
      to the paucity of mAbs issuing from these pathologies. We have isolated human IgG
      anti-alpha(IIb)beta(3) binding fragments using combinatorial libraries of single
      chain IgG created from the B cells of a GT and an AITP patient, both with serum
      Abs. Ab screening was performed using activated platelets or activated
      alpha(IIb)beta(3)-expressing Chinese hamster ovary cells. Sequencing of selected
      phage Abs showed that a broad selection of genes from virtually all V gene
      families had been used, indicating the diversity of the immune response. About
      one-half of the V(H) and V(L) segments of our IgG anti-alpha(IIb)beta(3)
      fragments displayed extensive hypermutations in the complementarity-determining
      region, supporting the idea that an Ag-driven immune response was occurring in
      both patients. The H chain complementarity-determining region 3 analysis of phage
      Abs revealed motifs other than the well-known RGD and KQAGDV integrin-binding
      sequences. To our knowledge, our study is the first to illustrate multiple human
      IgG anti-alpha(IIb)beta(3) reactivities and structural variations linked to the
      anti-platelet human immune response. Human alpha(IIb)beta(3) Abs preferentially
      directed against the activated form of the integrin were further characterized
      because platelet alpha(IIb)beta(3) inhibitors are potential therapeutic reagents
      for treating acute coronary syndromes. Currently available alpha(IIb)beta(3)
      antagonists do not specifically recognize the activated form of the integrin.

PMID- 11823542
TI  - Mechanism of action of combined short-term CTLA4Ig and anti-CD40 ligand in murine
      systemic lupus erythematosus.
AB  - Short-term combination therapy with the costimulatory antagonists CTLA4Ig and
      anti-CD40 ligand induces prolonged suppression of disease onset in New Zealand
      Black/New Zealand White F(1) systemic lupus erythematosus-prone mice. To
      determine the mechanism for this effect, 20- to 22-wk-old New Zealand Black/New
      Zealand White F(1) mice were treated with six doses each of CTLA4Ig and anti-CD40
      ligand Ab over 2 wk. Combination-treated mice, but not mice treated with either
      agent alone, had prolonged survival and the production of pathogenic IgG anti
      dsDNA Ab was suppressed. Twenty weeks after completion of treatment the frequency
      of activated B cells producing anti-dsDNA Ab was decreased, and the abnormal
      transition of T cells from the naive to the memory compartment was blocked.
      Combination treatment partially suppressed class switching and decreased the
      frequency of somatic mutations in the V(H)BW-16 gene, which is expressed by
      pathogenic anti-DNA Abs. Treated mice were still able to respond to the hapten
      oxazolone when it was given 8 wk after treatment initiation, and they mounted a
      somatically mutated IgG anti-oxazolone response that was noncross-reactive with
      dsDNA. Fifty to 60% of previously treated mice, but only 14% of previously
      untreated mice, responded within 2-3 wk to a second course of therapy given at
      the onset of fixed proteinuria and remained well for a further 3-4 mo. Although
      this treatment had no immediate effect on serum anti-dsDNA Abs or on the abnormal
      T cell activation observed in sick mice, 25% of treated mice lived for >18 mo
      compared with 5% of untreated controls. These results suggest that the effect of
      costimulatory blockade in remission induction must be mediated by a different
      mechanism than is demonstrated in the disease prevention studies.

PMID- 11823544
TI  - Paying for the NHS: are we asking the right question?

PMID- 11823543
TI  - Anti-sm autoantibodies in systemic lupus target highly basic surface structures
      of complexed spliceosomal autoantigens.
AB  - Autoantibodies directed against spliceosomal proteins are a common and specific
      feature of systemic lupus erythematosus. These autoantibodies target a collection
      of proteins, including Sm B, B', D1, D2, and D3. We define the common antigenic
      targets of Sm D2 and D3 and examine their role in spliceosomal autoimmunity. Our
      results define nine major common epitopes, five on Sm D2 and four on Sm D3. These
      epitopes have significantly higher (more basic) isoelectric points than do
      nonantigenic regions. In fact, this association is of sufficient power to make
      isoelectric point an excellent predictor of spliceosomal antigenicity. The
      crystallographic structure of Sm D2 and D3 is now partially described. The anti
      Sm D2 and D3 antigenic targets are located on the surface of the respective three
      dimensional complexed proteins, thereby suggesting that these epitopes are
      accessible in the native configuration. All but one of these nine epitopes
      conspicuously avoid the specific regions involved in intermolecular interactions
      within the spliceosomal complex. One of the D3 epitopes (RGRGRGMGR) has
      significant sequence homology with a major antigenic region of Sm D1 (containing
      a carboxyl-terminal glycine-arginine repeat), and anti-D3 Abs cross-react with
      this epitope of Sm D1. These results demonstrate that spliceosomal targets of
      autoimmunity are accessible on native structure surfaces and that cross-reactive
      epitopes, as well as structural associations of various spliceosomal Ags, may be
      involved in the induction of autoimmunity in systemic lupus.

PMID- 11823545
TI  - No excuses.

PMID- 11823546
TI  - A guide to creating your own patient-oriented website.

PMID- 11823548
TI  - Stigma in psychiatry.

PMID- 11823547
TI  - Adolescent treatment compliance in asthma.

PMID- 11823550
TI  - Unculturable bacteria--the uncharacterized organisms that cause oral infections.

PMID- 11823549
TI  - Oral bacterial disease and the science of cellular conversation.

PMID- 11823552
TI  - Back pain--whose responsibility?

PMID- 11823551
TI  - Alcohol abuse: prevalence and detection in a general hospital.
AB  - Despite a high prevalence of alcohol-related disabilities and the availability of
      cost-effective interventions, alcohol abuse and dependence commonly go undetected
      in hospital inpatients. In a university teaching hospital we compared three well
      validated screening methods for sensitivity and specificity-the Alcohol Use
      Disorders Identification Test (AUDIT, with various cut-off scores), CAGE (a four
      question screening tool), and a 10-question version of the Michigan Alcoholism
      Screening Test (BMAST). A subset of patients also completed the DSM IV structured
      clinical interview for diagnosis. 1133 adult patients were randomly selected from
      all hospital admissions, with exclusion of day cases and patients too ill to be
      interviewed. Two-thirds of the patients were interviewed, most of the remainder
      being unavailable at the time. 30% of the men and 8% of the women met the DSM IV
      criteria for alcohol abuse or dependence. Sensitivities and specificities of the
      screening tools were as follows: AUDIT (with cut-off score >8) 89% and 91%; CAGE
      77% and 99%; BMAST 37% and 100%. 255 case records of patients scoring above the
      cut-off on one or more questionnaires were subsequently reviewed. The admitting
      team recognized an alcohol problem in only 46, of whom 17 were referred for
      appropriate follow up. As in previous hospital surveys, alcohol abuse and
      dependence was not receiving proper attention. The most efficient screening tool
      was the CAGE questionnaire.

PMID- 11823553
TI  - Progressive subcutaneous emphysema and respiratory arrest.

PMID- 11823554
TI  - Hypocalcaemia during fusidic acid therapy.

PMID- 11823555
TI  - Suicide in a patient with symptomatic carotid occlusion.

PMID- 11823556
TI  - An umbilical nodule.

PMID- 11823557
TI  - Sampson Gamgee: a great Birmingham surgeon.

PMID- 11823558
TI  - Sherlock Holmes and a biological weapon.

PMID- 11823559
TI  - Did the "Pigeon Chested Man" have Marfan's syndrome?

PMID- 11823560
TI  - Clinical skills in final year medical students.

PMID- 11823561
TI  - Extradural haematoma with sinusitis.

PMID- 11823562
TI  - Extradural haematoma with sinusitis.

PMID- 11823563
TI  - Inappropriate admissions.

PMID- 11823564
TI  - 11 September and after.

PMID- 11823565
TI  - Missing vas.

PMID- 11823566
TI  - Missing vas.

PMID- 11823567
TI  - More on BSE/vCJD.

PMID- 11823568
TI  - High dietary lipids induce liver glucose-6-phosphatase expression in rainbow
      trout (Oncorhynchus mykiss).
AB  - To contribute to the understanding of the mechanisms involved in poor metabolic
      utilization of dietary carbohydrates by rainbow trout (Oncorhynchus mykiss), we
      explored in this study the effects of dietary lipids on the regulation of two
      hepatic key enzymes, i.e., glucokinase (GK, first enzyme of the glycolytic
      pathway) and glucose-6-phosphatase (G6Pase, last enzyme of the gluconeogenesis).
      Two groups of juvenile trout were pair-fed for 8 wk either a low (10%) or a high
      (25%) level of dietary lipids supplied as fish oil; the pair-feeding technique
      was adopted to vary fat intake while keeping the protein and carbohydrate intakes
      more or less constant. Fish fed the high level of dietary lipids had inefficient
      control of glycemia compared with fish fed the low level of lipids. Levels of
      dietary lipids did not affect GK activity even though there was a small increase
      of GK mRNA level at 3 h after feeding high levels of lipids. By contrast, the
      high level of dietary lipids significantly increased G6Pase mRNA expression at 3,
      6 and 12 h and enzyme activity at 6 h after food consumption. Thus, these data
      suggest that poor dietary carbohydrate utilization in rainbow trout may be
      related at least in part to increased hepatic glucose production under conditions
      of high dietary fat intake.

PMID- 11823569
TI  - Prenatal high protein exposure decreases energy expenditure and increases
      adiposity in young rats.
AB  - Epidemiologic results suggest that protein intake in infancy and later adiposity
      might be related. We examined whether high dietary protein exposure in utero
      and/or during postnatal life affects body fatness. Two groups of female rats were
      mated and pair-fed isocaloric high (40% protein; HP) or adequate protein (20%
      protein; AP) diets throughout pregnancy. The male offspring were suckled (3 wk)
      by foster mothers pair-fed HP or AP diets, resulting in 4 pre-/postnatal groups
      (AP-AP, AP-HP, HP-AP, HP-HP). Subsequently, they were pair-fed the same diets
      their nurses received during lactation until wk 9. Offspring of HP dams had a
      lower body weight on d 2 of life than their AP counterparts (7.6 +/- 0.7 vs. 8.3
      +/- 0.8 g; P < 0.001). HP-AP rats had a higher body weight than AP-AP controls at
      wk 3, 5, and 6 (P < 0.05), in contrast to HP-HP which did not differ from
      controls. Prenatal HP exposure resulted in a greater total and relative fat mass
      and decreased total energy expenditure at wk 9 (P < 0.05). Postnatal HP alone had
      no significant effect on body composition or metabolic rate. These results
      indicate that in utero exposure to a high protein level reprograms body weight
      and energy homeostasis.

PMID- 11823570
TI  - Insulin-like growth factor binding protein-2 gene expression can be regulated by
      diet manipulation in several tissues of young chickens.
AB  - The relationship between nutritional status and insulin-like growth factor
      binding protein-2 (IGFBP-2) gene expression in chickens was studied. Chickens (6
      wk old) were food deprived for 2 d and then refed. IGFBP-2 mRNA in the brain was
      significantly decreased by food deprivation and levels did not increase when
      birds were refed for 24 h. Gizzard and hepatic IGFBP-2 mRNA levels were
      significantly increased by food deprivation and decreased by refeeding. Any
      nutrients tested decreased hepatic IGFBP-2 gene expression. In kidney, IGFBP-2
      mRNA was detected but not influenced by food deprivation and refeeding. In
      another study, the influence of dietary protein source [isolated soybean protein
      vs. casein; crude protein (CP) 20%] and the supplementation of essential amino
      acids on IGFBP-2 gene expression of young chickens (5 wk old) was examined. The
      influence of feeding a low soybean protein diet (CP 5%) on tissue IGFBP-2 gene
      expression was also investigated. Hepatic IGFBP-2 mRNA was not detected in any
      group. Feeding the low protein diet for 7 d decreased brain IGFBP-2 mRNA level
      and increased gizzard IGFBP-2 level compared with chickens fed 20% protein diets.
      A significant interaction between protein source and amino acid supplementation
      was observed in gizzard IGFBP-2 mRNA level. In both casein-fed groups and in
      chickens fed 20% soybean protein diet without supplemental amino acids, the
      levels did not differ from one another or from the low protein diet-fed birds.
      The level was lower in chickens fed the amino acid-supplemented, 20% soybean
      protein diet. In conclusion, the response of IGFBP-2 gene expression to
      variations in nutritional status was rapid and different in several tissues of
      young chickens, which would help modulate the growth-promoting effect of
      circulating IGF-I by making the IGF-IGFBP complex.

PMID- 11823571
TI  - Plasma homocysteine levels in Taiwanese vegetarians are higher than those of
      omnivores.
AB  - Mild hyperhomocysteinemia is an independent risk factor for cardiovascular
      disease and may result from a deficiency of folate, vitamin B-6 or vitamin B-12.
      Because vitamin B-12 deficiency is often associated with vegetarianism, this
      study was designed to examine the effect of Taiwanese vegetarian diets on B
      vitamin status and plasma homocysteine levels. Female Buddhist lacto-vegetarians
      (n = 45; 31-45 y) and matched omnivores (n = 45) recruited in Hualien, Taiwan,
      were investigated. Taiwanese vegetarians consumed normal amount of folate, but
      only 21% of Taiwan Recommended Daily Nutrient Allowances (RDNA) values of vitamin
      B-12. Compared with the omnivores, the vegetarians had significantly higher
      levels of plasma folate (14.79 +/- 7.70 vs. 11.98 +/- 8.29 nmol/L), but lower
      levels of vitamin B-12 (207.7 +/- 127.1 vs. 403.5 +/- 138.9 pmol/L). Fasting
      plasma homocysteine levels were significantly higher in vegetarians than in
      omnivores (mean: 11.20 +/- 4.27 vs. 8.64 +/- 2.06 micromol/L; median: 10.5 vs.
      8.5 micromol/L). Fasting plasma homocysteine was inversely correlated with plasma
      folate and vitamin B-12 in the vegetarian group. Multiple regression analysis
      revealed that plasma folate, vitamin B-12 and creatinine were independent
      determinants of homocysteine variation and contributed to 38.6% of homocysteine
      variation in the vegetarians. Compared with the omnivores, vegetarians also had
      significantly lower serum levels of valine, isoleucine, leucine, lysine, alanine
      and arginine, but higher levels of glycine. In the vegetarian group, fasting
      plasma homocysteine correlated negatively with serum threonine, lysine,
      histidine, arginine and cystine, and these amino acids contributed to 38.7% of
      homocysteine variation. In conclusion, the Buddhist nuns who consumed a lacto
      vegetarian diet had mildly elevated fasting plasma homocysteine levels presumably
      due to lower levels of plasma vitamin B-12.

PMID- 11823572
TI  - Alpha- and beta-carotene from a commercial puree are more bioavailable to humans
      than from boiled-mashed carrots, as determined using an extrinsic stable isotope
      reference method.
AB  - The extent to which processing affects the carotene or vitamin A value of foods
      is poorly understood. An extrinsic reference method was used to estimate the mass
      of carotenes and vitamin A derived from various preparations made from the same
      lot of carrots. Using a repeated-measures design, nine healthy adult subjects
      consumed test meals of either carrot puree (commercial baby food) or boiled
      mashed carrots on separate days; six of the subjects also consumed a test meal of
      raw-grated carrot. Test meals supplied 34.7 micromol (18.6 mg) carrot beta
      carotene (beta C), plus 6 micromol deuterium-labeled retinyl acetate (d(4)-RA) in
      oil solution. Baseline-adjusted carotene and retinyl ester (R-ester) area-under
      curve (AUC) responses in the triacylglycerol-rich lipoprotein (TRL) fraction (0
      8.5 h) were determined using HPLC and gas chromatography-mass spectrometry. The
      masses of absorbed beta C, alpha-carotene (alpha C) and R-ester were estimated by
      comparing their AUC values with that of deuterium-labeled retinyl ester (d(4)-R
      ester), assuming the latter represented 80% of the d(4)-RA reference dose.
      Absorption of beta C and alpha C was approximately twofold greater from carrot
      puree than from boiled-mashed carrots, whereas the retinol yield was only
      marginally (P = 0.11) influenced by treatment. Carotene and R-ester absorption
      from raw-grated carrot was intermediate to, and did not differ significantly from
      the cooked preparations. The vitamin A yield (puree, 0.53 mg; boiled-mashed, 0.44
      mg) of cooked carrot containing 18.6 mg beta C was substantially less than that
      predicted by current convention and limited primarily by intestinal carotene
      uptake. Processing can therefore significantly improve bioavailability of carrot
      carotenes, and in some cases influence the carotene value more than the intrinsic
      vitamin A value.

PMID- 11823573
TI  - Dietary supplementation with aged garlic extract reduces plasma and urine
      concentrations of 8-iso-prostaglandin F(2 alpha) in smoking and nonsmoking men
      and women.
AB  - F(2)-isoprostanes are recently described prostaglandin F isomers produced by
      cyclooxygenase-independent free radical peroxidation of arachidonic acid. Their
      quantification in plasma and urine is a sensitive and specific indicator of lipid
      peroxidation and, hence, of oxidative stress in vivo. Some components of garlic
      are known to possess antioxidant properties. Thus, we have investigated the
      effect of dietary supplementation with aged garlic extract (AGE; Kyolic; Wakunaga
      of America, Mission Viejo, CA) on the plasma and urine concentrations of the F(2)
      isoprostane 8-iso-prostaglandin F(2 alpha) (8-iso-PGF(2 alpha)). Because smokers
      are exposed to increased oxidative stress, this study was performed in both
      smoking and nonsmoking subjects. Plasma and urine concentrations of 8-iso-PGF(2
      alpha) in nonsmoking individuals were 1.25 +/- 0.19 nmol/L and 272 +/- 53
      pmol/mmol of creatinine, respectively. In age- and sex-matched smokers, plasma
      and urine concentrations of 8-iso-PGF(2 alpha) were 58% and 85% higher,
      respectively. Dietary supplementation with AGE for 14 d reduced plasma and urine
      concentrations of 8-iso-PGF(2 alpha) by 29% and 37% in nonsmokers and by 35% and
      48% in smokers. Fourteen days after cessation of dietary supplementation, plasma
      and urine concentrations of 8-iso-PGF(2 alpha) returned to values not different
      from those before ingestion of AGE in both groups. Thus, dietary supplementation
      with AGE may be useful in reducing oxidative stress in humans.

PMID- 11823574
TI  - Polyphenols from alcoholic apple cider are absorbed, metabolized and excreted by
      humans.
AB  - We determined the uptake and excretion of low doses of polyphenols in six
      subjects who each consumed 1.1 L of an alcoholic cider beverage. Over a 24-h
      period, no phloretin was detected in plasma (detection limit = 0.036 micromol/L),
      but 21 +/- 5% of the dose (4.8 mg) was excreted in the urine. In contrast, from a
      low dose of 1.6-mg quercetin equivalents, no quercetin was found in urine or
      plasma, but 3'-methyl quercetin was detected in plasma [C(max) (maximum
      concentration) = 0.14 +/- 0.19 micromol/L; range: 0 to 0.44 micromol/L]. No
      flavanol monomers (dose of free (+)-catechin and (-)-epicatechin = 3.5 mg) were
      detected in urine or plasma (detection limit: 0.01 micromol/L). Caffeic acid
      (total dose including esters = 11 mg) was detected only in plasma within 2 h,
      with C(max) = 0.43 +/- 0.3 micromol/L (range: 0.18 to 0.84 micromol/L). An almost
      3-fold increase in hippuric acid was detected in 24-h urine (74 +/- 29
      micromol/L; range: 38-116 micromol/L), compared with a prestudy value of 19 +/- 9
      micromol/L. These data show that polyphenols are taken up from cider, that
      phloretin is excreted in the urine and suggest that low doses of quercetin are
      extensively methylated in humans.

PMID- 11823575
TI  - Food restriction normalizes chylomicron remnant metabolism in murine models of
      obesity as assessed by a novel stable isotope breath test.
AB  - Evidence is increasing that defective metabolism of postprandial remnants of
      triglyceride-rich lipoproteins contributes to atherogenesis. In obesity,
      postprandial lipemia is increased by mechanisms that are not currently
      established. In the present study, a recently developed (13)CO(2) breath test was
      used to assess the metabolism of chylomicron remnants (CR) in obese mice. Six
      murine obese models ob/ob, fat/fat, New Zealand Obese (NZO), db/db, gold
      thioglucose (GTG)-treated and agouti (A(y)) were studied. All obese mice were
      hyperphagic and their breath test metabolism was markedly impaired (P < 0.01)
      compared with control, nonobese mice. The breath test was also impaired (P <
      0.01) in all obese mice except A(y) mice after 24-h food deprivation. However,
      after restriction to the food intake of paired control mice for 6 wk, the breath
      test in all obese mice improved to values of control, nonobese mice. The obese
      NZO, fat/fat and ob/ob mice had significant (P < 0.02) weight loss when food
      restricted, whereas A(y), GTG, and db/db mice did not. In all obese mice, plasma
      cholesterol levels decreased (P < 0.02) after the 6-wk period of food
      restriction. Plasma triglyceride levels significantly decreased (P < 0.02) in
      NZO, GTG and db/db mice, but not in other obese mice. Plasma glucose levels were
      significantly decreased (P < 0.02) after the 6-wk period in the obese mice except
      for the A(y) and NZO mice; levels were greater in food-restricted db/db mice.
      Although some of the obese models such as db/db were diabetic, our data suggest
      that the defective breath test was independent of diabetes because all obese and
      diabetic models responded similarly to food restriction. Impaired hepatic
      catabolism of CR was excluded as a cause of the abnormal breath tests. In
      summary, the impairment (P < 0.05) in remnant metabolism as assessed by the
      breath test in obese mice was corrected by food restriction, associated with
      improvements in plasma glucose, triglyceride and cholesterol levels.

PMID- 11823576
TI  - The deposition of conjugated linoleic acids in eggs of laying hens fed diets
      varying in fat level and fatty acid profile.
AB  - The objective of this study was to investigate the incorporation of conjugated
      linoleic acid (CLA) into eggs and its effect on the fatty acid metabolism when
      layers are fed diets with different fat sources and fat levels. Layers were fed
      either a low fat diet (LF) or one of three high fat diets based on soybean oil
      (SB), animal fat (AF) or flaxseed oil (FSO). CLA was added at a concentration of
      1 g/100 g feed from two different CLA premixes with a different CLA profile. For
      the trial, 144 laying hens were allocated to 12 treatments (4 basal fat sources x
      3 CLA treatments) with 3 replicates of 4 hens each. No significant differences
      were observed in feed intake, egg weight, feed conversion or laying rate between
      chickens fed control and CLA-supplemented diets. Differences in yolk fat,
      cholesterol or yolk color were not clearly related to the dietary CLA. However,
      the supplementation of CLA to the diets had clear effects on the fatty acid
      composition, i.e., a decrease in monounsaturated fatty acids (MUFA) and an
      increase in saturated fatty acids (SFA) was observed, whereas the polyunsaturated
      fatty acids (PUFA) content were essentially unaffected. The results suggest that
      CLA may influence the activity of the desaturases to a different extent in the
      synthesis of (n-6) and (n-3) long-chain fatty acids. These effects of CLA depend
      on the level of (n-6) and (n-3) fatty acids available in the feed. The apparent
      deposition rate (%) is clearly higher for the c9, t11 isomer than for the t10,
      c12 isomer. Adding CLA to layers diets rich in (n-3) fatty acids produces eggs
      that could promote the health of the consumer in terms of a higher intake of (n
      3) fatty acids and CLA.

PMID- 11823577
TI  - Skeletal unloading and dietary copper depletion are detrimental to bone quality
      of mature rats.
AB  - This study was designed to examine the skeletal response to copper depletion and
      mechanical unloading in mature animals. In a 2 x 2 experimental design, 5.5-mo
      old male Sprague-Dawley rats (n = 36) consumed either the control (AIN-93M) or Cu
      depletion ((-)Cu) diet beginning 21 d before suspension and throughout the
      remainder of the study. Half of the rats in each dietary treatment group were
      either tail-suspended (TS) or kept ambulatory (AMB) for 28 d. Lower bone mineral
      densities (BMD) of 5th lumbar vertebra (L5) (P < 0.05) and femur were observed
      with (-)Cu and TS, but no differences were noted in the BMD of the humerus.
      Mechanical strength in the femur and vertebra decreased in response to TS, but
      were unaffected by copper depletion. Urinary deoxypyridinoline, an index of bone
      resorption, was significantly greater in TS rats, but unaltered by (-)Cu. No
      changes in serum or bone alkaline phosphatase activity, an indicator of bone
      formation, were observed. Our findings suggest that TS and (-)Cu decreased BMD in
      unloaded femur and vertebra but had no effect on normally loaded humerus. Bone
      loss with TS appeared to be related to accelerated bone resorption. Alterations
      in bone metabolism and bone mechanical properties in the mature skeleton
      resulting from (-)Cu warrant further investigation.

PMID- 11823578
TI  - Porcine intestinal metabolism of excess vitamin a differs following vitamin a
      supplementation and liver consumption.
AB  - Vitamin A is a well-established teratogen in all animal species. A number of case
      reports also suggest a teratogenic potential of vitamin A in humans. A possible
      teratogenic risk of dietary liver vitamin A intake, the kinetics of vitamin A and
      its metabolites in humans after intake of either a vitamin A supplement or a
      liver meal have been studied. Major differences were described for the kinetics
      of all-trans-retinoic acid (all-trans-RA), which occurred at much higher
      concentrations after supplementation than after liver consumption. Therefore, we
      investigated whether the intestine may be responsible for the differences in
      vitamin A metabolism after supplementation or liver feeding. We found that
      cytosolic fractions of porcine enterocytes oxidized retinol to all-trans-RA in
      vitro with a K(m) of 94-96 micromol/L and a V(max) of 7.9-8.6 pmol/(min x mg
      protein). In an in vivo approach, the portal vein and the central vein (external
      jugular vein) of a pig were cannulated. In two subsequent experiments, the pig
      was given a vitamin A supplement or liver. Plasma samples were taken from portal
      and central veins. Comparison of retinoid levels in these veins indicated that
      all-trans-RA was already formed from supplemental vitamin A in the intestine and
      released into the systemic circulation. Two major metabolic pathways were
      additionally present in the pig, leading to the formation of glucuronides of all
      trans-RA and retinol itself. Our results indicate that intestinal metabolism
      contributes to the elevated levels of all-trans-RA in the systemic circulation
      after supplementation with vitamin A, but not after consumption of liver.

PMID- 11823579
TI  - Dietary L-carnitine supplementation in obese cats alters carnitine metabolism and
      decreases ketosis during fasting and induced hepatic lipidosis.
AB  - This study was designed to determine whether dietary carnitine supplement could
      protect cats from ketosis and improve carnitine and lipid metabolism in
      experimental feline hepatic lipidosis (FHL). Lean spayed queens received a diet
      containing 40 (CL group, n = 7) or 1000 (CH group, n = 4) mg/kg of L-carnitine
      during obesity development. Plasma fatty acid, beta-hydroxybutyrate and
      carnitine, and liver and muscle carnitine concentrations were measured during
      experimental induction of FHL and after treatment. In control cats (CL group),
      fasting and FHL increased the plasma concentrations of fatty acids two- to
      threefold (P < 0.0001) and beta-hydroxybutyrate > 10-fold (from a basal 0.22 +/-
      0.03 to 1.70 +/- 0.73 after 3 wk fasting and 3.13 +/- 0.49 mmol/L during FHL). In
      carnitine-supplemented cats, these variables increased significantly (P < 0.0001)
      only during FHL (beta-hydroxybutyrate, 1.42 +/- 0.17 mmol/L). L-Carnitine
      supplementation significantly increased plasma, muscle and liver carnitine
      concentrations. Liver carnitine concentration increased dramatically from the
      obese state to FHL in nonsupplemented cats, but not in supplemented cats, which
      suggests de novo synthesis of carnitine from endogenous amino acids in control
      cats and reversible storage in supplemented cats. These results demonstrate the
      protective effect of a dietary L-carnitine supplement against fasting ketosis
      during obesity induction. Increasing the L-carnitine level of diets in cats with
      low energy requirements, such as after neutering, and a high risk of obesity
      could therefore be recommended.

PMID- 11823580
TI  - Mongolian gerbils can utilize provitamin-A carotenoids in deep-fried carrot
      chips.
AB  - Deep-fried carrot chips, containing provitamin-A carotenes, were developed as an
      alternative mode of dietary intervention to combat vitamin A deficiency. The
      biological use of carotenoids in this product as vitamin A precursors was
      evaluated in Mongolian gerbils. Male 4-wk-old gerbils were fed a diet containing
      all essential nutrients for 1 wk. Then six gerbils were killed, and the remaining
      gerbils were fed the diet without vitamin A for 6 wk to produce marginal vitamin
      A deficiency. After depletion, six gerbils were killed and the remainder divided
      into four groups of 12 gerbils each and fed vitamin A-containing diet (+VA), beta
      carotene-containing diet (BC), carrot chip-containing diet (CC), or diet
      containing no vitamin A/provitamin-A carotenes (-VA). The first three diets
      contained approximately 6 microg RE/g. Six gerbils from each group were killed
      after 2 wk of consuming these diets, and 6 after 4 wk. Final body weight and
      weekly food consumption did not differ among groups after 2 or 4 wk of repletion.
      Total liver vitamin A stores of BC and CC gerbils killed after 4 wk of repletion
      were not different from those of gerbils killed before depletion, but those of 
      VA gerbils were significantly lower (P < 0.05) and those of +VA gerbils were
      significantly higher (P < 0.05). Plasma retinol levels of gerbils killed after 4
      wk of repletion, including the -VA group, did not differ. Total liver alpha- and
      beta-carotenes and 9-cis beta-carotene contents of the CC group were
      significantly higher (P < 0.05) than in the BC group after 4 wk of repletion.
      This carrot chip product effectively reversed vitamin A deficiency in gerbils.

PMID- 11823581
TI  - Intestinal absorption and lymphatic transport of a high gamma-linolenic acid
      canola oil in lymph fistula Sprague-Dawley rats.
AB  - A new canola strain capable of producing >30% gamma-linolenic acid [GLA, 18:3(n
      6)] in the seed oil has been developed in our laboratories. This study compares
      the intestinal absorption and lymphatic transport of this newly developed high
      GLA content canola oil (HGCO) with traditional GLA-rich borage oil (BO) using a
      lymph fistula rat model. To assess the extent that 1 mL of GLA in the
      supplemented oil was absorbed and transported, the fatty acid compositions of
      triglycerides in mesenteric lymph were compared over a 24-h collection period.
      The digestion, uptake and lymphatic transport of HGCO and the normal physiologic
      changes associated with fat absorption (e.g., lymph flow and an increase in
      lymphatic endogenous lipids outputs, triglycerides, cholesterol and
      phospholipids) were similar in the HGCO-and the BO-fed rats. The original
      differences in gamma-linolenic acid content in HGCO and BO were preserved in the
      fatty acid composition of the rats' lymph lipid. We conclude that the HGCO
      derived from the genetically modified canola plant is absorbed and transported
      into lymph similarly to BO.

PMID- 11823583
TI  - Supplementation of plant sterols and minerals benefits obese Zucker rats fed an
      atherogenic diet.
AB  - In most hypertensive rat models, serum total cholesterol is typically low and the
      cholesterol is primarily in the HDL rather than the LDL fraction. This difference
      from humans usually makes these animals unsuitable for experimental
      atherosclerosis studies. In the present study, we induced severe
      hypercholesterolemia including a 10-fold increase in serum LDL cholesterol,
      endothelial dysfunction and hypertension as well as vascular and renal damage in
      obese Zucker rats by feeding a human-type high fat, high cholesterol and high
      salt diet (butter 18, cholesterol 1 and NaCl 6 g/100 g dry weight).
      Supplementation of this atherogenic diet with plant sterols (1 g/100 g) and
      replacing the NaCl partially by calcium, magnesium and potassium effectively
      prevented the diet-induced increases in total and LDL cholesterols and 24-h
      systolic and mean blood pressures, and markedly improved endothelial function.
      Plant sterols and the minerals also protected against vascular and renal damage
      and extended the life span of the obese Zucker rats by 60% compared with the rats
      fed the atherogenic diet. Our findings suggest that human-type cardiovascular
      disorders can be induced in obese Zucker rats by feeding a human-type atherogenic
      diet. This seems to be a suitable animal model for experimental studies on
      atherosclerosis and hypertension as well as for evaluating new dietary approaches
      to reducing cardiovascular risk.

PMID- 11823582
TI  - Substituting fish oil with crude palm oil in the diet of Atlantic salmon (Salmo
      salar) affects muscle fatty acid composition and hepatic fatty acid metabolism.
AB  - Supplies of marine fish oils (FO) are limited and continued growth in aquaculture
      production dictates that substitutes must be found that do not compromise fish
      health and product quality. In this study the suitability of crude palm oil (PO)
      as a replacement for FO in diets of Atlantic salmon was investigated. Duplicate
      groups of Atlantic salmon post-smolts were fed four practical-type diets in which
      the added lipid was either 100% FO and 0% crude PO (0% PO); 75% FO and 25% PO
      (25% PO); 50% FO and 50% PO (50% PO); and 100% PO, for 30 wk. There were no
      effects of diet on growth rate or feed conversion ratio nor were any
      histopathological lesions found in liver, heart or muscle. Lipid deposition was
      greatest in fish fed 0% PO and was significantly greater than in fish fed 50% and
      100% PO. Fatty acid compositions of muscle total lipid were correlated with
      dietary PO inclusion such that the concentrations of 16:0, 18:1(n-9), 18:2(n-6),
      total saturated fatty acids and total monoenoic fatty acids increased linearly
      with increasing dietary PO. The concentration of eicosapentaenoic acid [20:5(n
      3)] was reduced significantly with increasing levels of dietary PO but the
      concentration of docosahexaenoic acid [22:6(n-3)] was significantly reduced only
      in fish fed 100% PO, compared with the other three treatments. Similar diet
      induced changes were seen in liver total lipid fatty acid compositions. Hepatic
      fatty acid desaturation and elongation activities were approximately 10-fold
      greater in fish fed 100% PO than in those fed 0% PO. This study suggests that PO
      can be used successfully as a substitute for FO in the culture of Atlantic salmon
      in sea water. However, at levels of PO inclusion above 50% of dietary lipid,
      significant reductions in muscle 20:5(n-3), 22:6(n-3) and the (n-3):(n-6) PUFA
      ratio occur, resulting in reduced availability of these essential (n-3) highly
      unsaturated fatty acids to the consumer.

PMID- 11823584
TI  - Soymilk products affect ethanol absorption and metabolism in rats during acute
      and chronic ethanol intake.
AB  - In this study we evaluated the effects of soy products on ethanol metabolism
      during periods of acute and chronic consumption in rats. Gastric ethanol content
      and blood ethanol and acetaldehyde concentrations were investigated after the
      oral administration of ethanol (34 mmol/kg) plus soy products such as soymilk
      (SM) or fermented soymilk (FSM). The gastric ethanol concentration of the FSM
      group was greater than that of the control group, whereas portal and aortal blood
      ethanol concentrations of the FSM group were lower than in controls. The aortal
      acetaldehyde concentration in the FSM group was lower than that of the control
      group. The direct effect of isoflavones on liver function was investigated by
      using hepatocytes isolated from untreated rats. Genistein (5 micromol/L)
      decreased ethanol (P = 0.045) and tended to decrease acetaldehyde (P = 0.10)
      concentrations in the culture filtrate. Some variables of ethanol metabolism in
      the liver were investigated after chronic ethanol exposure for 25 d. Rats
      consumed a 5% ethanol fluid plus the SM diet, the FSM diet or a control diet.
      Microsomal ethanol oxidizing activity was significantly lower in the FSM group
      than the control group. Furthermore, cytosolic glutathione S-transferase activity
      was higher in the SM and FSM groups than in the control group. Acetaldehyde
      dehydrogenase activity (low K(m)) in the FSM group (P = 0.15), but not in the SM
      group (P = 0.31), tended to be greater than in the control group. The amount of
      thiobarbituric acid reacting substances in the liver of the SM and FSM groups
      tended to be less than that of the control group (P = 0.18 and 0.10,
      respectively). These results demonstrate that soymilk products inhibit ethanol
      absorption and enhance ethanol metabolism in rats.

PMID- 11823585
TI  - Histidine content of low-molecular-weight beef proteins influences nonheme iron
      bioavailability in Caco-2 cells.
AB  - The objective of this study was to isolate and characterize beef muscle proteins
      that enhance nonheme iron bioavailability. Beef sirloin was cooked, lyophilized
      and reconstituted with water before in vitro digestion. After centrifugation, the
      digest supernatant was sequentially ultrafiltered using 10- and 1-kDa molecular
      weight cut-off membranes. Nonheme iron bioavailability was assessed by Caco-2
      cell monolayer (59)Fe uptake using an extrinsic labeling method. All
      ultrafiltration fractions significantly (P < 0.001) increased iron solubility at
      pH 6.0, compared with the blank. However, iron uptake was significantly (P <
      0.001) greater than the blank only in the presence of the 1-kDa retentate (1KR).
      Therefore, the 1KR was chosen for further analysis. Immobilized metal affinity
      chromatography (IMAC) of the 1KR yielded four fractions, i.e., three distinct
      fractions (F1, F3, F4) and one fraction (F2) comprised of a few closely
      associated peaks. All four IMAC fractions resulted in significantly (P < 0.001)
      greater (two- to fivefold) iron solubility at pH 6.0, compared with the blank.
      Iron uptake with F2 and F4 was significantly greater than the blank (P < 0.001
      and P < 0.05, respectively). Gel electrophoresis and matrix-assisted laser
      desorption/ionization analysis illustrated that F1-F4 contained many peptides
      ranging from 1- to 7-kDa. Amino acid composition analysis revealed that histidine
      concentration increased progressively from F1 to F4, corresponding to a general,
      but not parallel increase in iron solubility and uptake. Our results suggest that
      the enhancement of nonheme iron absorption by beef may be due to peptides
      produced during gastrointestinal digestion and that histidine content may be
      important.

PMID- 11823586
TI  - The concentrations and ratio of dietary calcium and phosphorus influence
      development of nephrocalcinosis in female rats.
AB  - Nephrocalcinosis (NC) in female rats can complicate the interpretation of
      nutritional or toxicological studies involving the kidney. Recent reformulations
      of standardized rodent diets such as AIN-93G and NTP-2000 sought to optimize the
      dietary Ca:P ratio, an important etiologic factor in NC. The effect of increasing
      intakes of Ca and P together at their optimal molar ratio has not been
      systematically studied. Weanling female and male Sprague-Dawley rats were fed
      modified AIN-93G diets containing Ca and P at AIN-93G diet concentrations (5 g Ca
      + 3 g P/kg diet), with multiples of Ca and P at the same ratio (1.5x = 7.5 g Ca +
      4.5 g P, 2.5x = 12.5 g Ca + 7.5 g P, 4.0x = 20.0 g Ca + 12.0 g P/kg diet), or Ca
      and P at concentrations found in the AIN-76A diet (5 g Ca + 5 g P/kg diet), for
      16 wk. Incidence and severity of NC and kidney Ca concentration in female rats
      increased with dietary Ca and P, although not to levels in female rats fed at the
      AIN-76A Ca:P ratio. Male rats showed limited evidence of kidney Ca accumulation
      or NC. The concentrations of dietary Ca and P, as well as the ratio of these two
      elements, affected development of NC in female rats.

PMID- 11823587
TI  - The daily oral administration of high doses of trans-resveratrol to rats for 28
      days is not harmful.
AB  - trans-3,5,4'-Trihydroxystilbene (trans-resveratrol) is a phytochemical present in
      peanuts, grapes and wine with beneficial effects such as protection against
      cardiovascular disease and cancer prevention. The purpose of this study was to
      evaluate whether high doses of trans-resveratrol have harmful effects on Sprague
      Dawley rats. trans-Resveratrol was administered orally to male rats for 28 d at a
      dose of 20 mg/(kg x d), 1000 times the amount consumed by a 70-kg person taking
      1.4 g of trans-resveratrol/d. Body weight, and food and water consumption did not
      differ between rats treated with trans-resveratrol and the control group.
      Hematologic and biochemical variables were not affected by the treatment.
      Histopathologic examination of the organs obtained at autopsy did not reveal any
      alterations. These results support the view that repeated consumption of trans
      resveratrol at 20 mg/(kg x d) does not adversely affect the variables tested in
      rats.

PMID- 11823588
TI  - Dietary fish oil suppresses experimental immunoglobulin a nephropathy in mice.
AB  - Dietary fish oil (FO) supplementation reportedly retards the progression of renal
      disease in patients with immunoglobulin (Ig)A nephropathy (IgAN), the most common
      glomerulonephritis worldwide. Using an experimental mouse model in which early
      immunopathological hallmarks of IgAN are induced by the mycotoxin vomitoxin (VT),
      the ameliorative effects of FO ingestion on this disease were evaluated in two
      studies. In Study 1, the capacity of VT to induce IgAN was evaluated in mice fed
      for 12 wk AIN-76A diets containing 50 g/kg corn oil (CO), 50 g/kg CO plus 9 mg/kg
      tert butylhydroquinone (TBHQ), or 5 g/kg CO plus 45 g/kg menhaden FO that
      contained 200 mg/kg TBHQ. Serum IgA, serum IgA immune complexes and kidney
      mesangial IgA deposition were greater in mice fed VT + CO compared with the CO
      control group, whereas all three variables were significantly attenuated in mice
      fed VT + FO. Although TBHQ also had attenuating effects, these were significantly
      less than those for the VT + FO group. In Study 2, the effects of feeding
      modified AIN 93G diets containing either 70 g/kg CO or 10 g/kg CO plus 60 g/kg FO
      for 20 wk on VT-induced IgAN were compared. Again, consumption of FO attenuated
      all three immunopathological variables. In addition, spleen cell cultures from
      the VT + FO group produced markedly less IgA than those cultures from mice fed VT
      + CO. Taken together, the results suggested that diets containing FO may impair
      early immunopathogenesis in VT-induced IgAN and that this was not totally
      dependent on the presence of the antioxidant TBHQ.

PMID- 11823589
TI  - Zinc status affects neurotransmitter activity in the paraventricular nucleus of
      rats.
AB  - Alterations in neurochemical activity in the paraventricular nucleus (PVN) of the
      hypothalamus may account for decreased intake of zinc-deficient diets. Male
      Sprague-Dawley rats were fed zinc-deficient (ZD) or zinc-adequate (ZA) diet for
      14 d before samples of extracellular fluid in the PVN were collected by
      microdialysis or push-pull perfusion. A third set of rats was pair-fed (PF) an
      amount of ZA diet equal to the intake of ZD rats. Samples were collected over a 2
      h period spanning the transition from light to dark. All rats then consumed the
      zinc adequate diet ad libitum for 3 d before a second set of samples was
      collected. The increase in extracellular norepineprhrine (NE) during h 1 of the
      dark period to 147 +/- 13% of baseline (P < 0.05) was apparent only in ZA rats at
      d 14. After the 3-d repletion period, the increase in NE at dark onset occurred
      in all three groups. An increase in extracellular neuropeptide Y (NPY) at dark
      onset to 174 +/- 32% of baseline in rats fed ZA (P < 0.01) was measured in all
      three groups at both d 14 and 17. Basal NPY concentrations were significantly
      elevated in PF rats on d 14 (7.45 +/- 2.01 vs. 0.58 +/- 0.23 pmol/L, P = 0.01)
      and returned to ZA levels by d 17. The activities of the NE and NPY systems in
      the PVN were altered in rats fed a zinc-deficient diet; however, it is unclear
      whether the disruption in the NE and NPY neural systems in the PVN results in the
      altered feeding behavior accompanying zinc deficiency.

PMID- 11823590
TI  - Dietary intake of phytoestrogens is associated with a favorable metabolic
      cardiovascular risk profile in postmenopausal U.S.women: the Framingham study.
AB  - Hypertension, central obesity and dyslipidemia are associated with high
      cardiovascular risk. Estrogen therapy in women has beneficial effects on some of
      these metabolic cardiovascular risk factors. It is not known whether dietary
      estrogens have similar effects, especially in Western populations. We studied the
      association between dietary phytoestrogen intake and metabolic cardiovascular
      risk factors in postmenopausal women. For this purpose, 939 postmenopausal women
      participating in the Framingham Offspring Study were included in this cross
      sectional study. Mean blood pressure, waist-hip ratio (WHR) and lipoprotein
      levels were determined in quartile categories of dietary phytoestrogen
      (isoflavones and lignans) intake, determined by a food-frequency questionnaire.
      In addition, a metabolic syndrome score was defined according to WHO criteria
      (range 0-6). The WHR was lower in women in the highest quartile of intake of
      lignans compared with the lowest [-0.017; 95% confidence interval (CI) -0.030 to 
      0.0016]. In the highest quartile of intake of isoflavones, plasma triglyceride
      levels were 0.16 mmol/L lower (95% CI, -0.30 to -0.02) compared with the lowest
      quartile of isoflavones; for lignan intake, this difference was 0.23 mmol/L (95%
      CI, -0.37 to -0.09). In the highest quartile of isoflavone intake, the mean
      cardiovascular risk factor metabolic score was 0.43 points lower (95% CI, -0.70
      to -0.16) than the lowest quartile. The difference in this score between the
      extreme quartiles of intake of lignans was -0.55 points (95% CI, -0.82 to -0.28).
      In conclusion, high intake of phytoestrogens in postmenopausal women appears to
      be associated with a favorable metabolic cardiovascular risk profile.

PMID- 11823591
TI  - The relationship between riboflavin and plasma total homocysteine in the
      Framingham Offspring cohort is influenced by folate status and the C677T
      transition in the methylenetetrahydrofolate reductase gene.
AB  - Methylenetetrahydrofolate reductase (MTHFR) catalyzes the synthesis of 5
      methyltetrahydrofolate, the methyl donor for remethylation of homocysteine to
      methionine. The C677T MTHFR polymorphism is associated with mild
      hyperhomocysteinemia, but only in the presence of low folate status. Because
      MTHFR contains flavin adenine dinucleotide (FAD) as a prosthetic group,
      riboflavin status may also influence homocysteine metabolism. The objective of
      this study was to examine the association between riboflavin status and fasting
      plasma total homocysteine (tHcy) concentration while also considering MTHFR C677T
      genotype and folate status. The study was conducted using fasting plasma samples
      (n = 450) from the fifth examination of the Framingham Offspring Study cohort.
      All persons with the TT genotype and age- and sex-matched sets of individuals
      with the CT and CC genotypes were selected for determination of plasma riboflavin
      and flavin mono- and dinucleotide levels. Plasma riboflavin was associated with
      tHcy concentrations, but the association was largely confined to persons with
      plasma folate <12.5 nmol/L and TT genotype. In these persons, the mean tHcy among
      individuals with riboflavin levels <6.89 nmol/L was 14.5 micromol/L, whereas the
      mean tHcy for those with riboflavin > or = 11 nmol/L was 11.6 micromol/L (P-trend
      <0.03). Plasma flavin nucleotides were unrelated to tHcy concentrations. Our data
      suggest that riboflavin status may affect homocysteine metabolism, but only in a
      small segment of the population who have both low folate status and are
      homozygotes for the MTHFR C677T mutation.

PMID- 11823592
TI  - The Chilean flour folic acid fortification program reduces serum homocysteine
      levels and masks vitamin B-12 deficiency in elderly people.
AB  - Hyperhomocysteinemia is considered a risk factor for cardiovascular disease and
      is prevalent in the elderly. Supplementation with folic acid, vitamin B-6 and B
      12 lowers homocysteine levels. In January 2000, the Chilean government initiated
      a flour folic acid fortification program to decrease the occurrence of neural
      tube defects. The aim of this study was to evaluate the effect of this program on
      serum homocysteine and folate levels in elderly subjects after 6 mo. A total of
      108 elderly people were studied. We measured serum folate, homocysteine and
      vitamin B-12 levels before the fortification started and 6 mo later. At baseline,
      folate deficiency (<6.8 nmol/L) was present in 1.8%, vitamin B-12 deficiency
      (<165 pmol/L) in 27.6% and hyperhomocysteinemia (>14 micromol/L) in 31% of the
      sample. Six months later, serum folate levels increased from 16.2 +/- 6.2 to 32.7
      +/- 7.1 nmol/L (P < 0.001), homocysteine levels decreased from 12.95 +/- 3.7 to
      11.43 +/- 3.6 micromol/L (P < 0.001) and vitamin B-12 levels were unchanged.
      Flour fortification with folic acid had a moderate lowering effect on
      homocysteine levels. Given that vitamin B-12 deficiency was more common than
      folate deficiency, it may be more appropriate to add vitamin B-12 to food, at
      least in foods for this age group.

PMID- 11823593
TI  - Dietary selenite and azadeoxycytidine treatments affect dimethylhydrazine-induced
      aberrant crypt formation in rat colon and DNA methylation in HT-29 cells.
AB  - Several observations implicate a role for altered DNA methylation in cancer
      pathogenesis. The global level of DNA methylation is generally lower; however,
      DNA methyltransferase (Dnmt1) activity is usually higher in tumor cells than in
      normal cells. The purpose of this study was to investigate whether the Dnmt1
      inhibitor, 5-aza-2'-deoxycytidine (aza-dC) would alter the effect of dietary
      selenium on the formation of aberrant crypts. Weanling rats (n = 60) were fed
      three concentrations of selenium (deficient, 0.1 and 2.0 mg/kg diet) in a Torula
      yeast-based diet. Half of the rats were injected weekly with aza-dC (1 mg/kg,
      subcutaneously) and half were injected with the vehicle control (PBS). After 3.5
      wk of consuming the experimental diets, the rats were given two injections of
      dimethylhydrazine (DMH; 25 mg/kg, intraperitoneally). Rats fed the selenium
      deficient diet and injected with PBS had significantly (P < 0.006) more aberrant
      crypts than rats fed 0.1 or 2.0 mg selenium/kg diet (244 +/- 21 vs. 165 +/- 9 and
      132 +/- 14, respectively). In contrast, when rats were injected with aza-dC,
      there was a significant (P < 0.0001) reduction in aberrant crypt formation and
      dietary selenium had no effect (62 +/- 8 vs. 77 +/- 13 vs. 54 +/- 8, in rats fed
      0, 0.1 and 2.0 mg selenium/kg diet, respectively). HT-29 cells cultured in the
      absence of selenium had significantly hypomethylated DNA but significantly more
      Dnmt1 protein expression than cells cultured in the presence of 1 or 2 micromol/L
      selenium. These results suggest that aza-dC treatment may protect selenium
      deficient rats against carcinogen-induced aberrant crypt formation.

PMID- 11823594
TI  - Piceatannol, a natural analog of resveratrol, inhibits progression through the S
      phase of the cell cycle in colorectal cancer cell lines.
AB  - Piceatannol, a naturally occurring analog of resveratrol, was previously
      identified as the active ingredient in herbal preparations in folk medicine and
      as an inhibitor of p72(Syk). We studied the effects of piceatannol on growth,
      proliferation, differentiation and cell cycle distribution profile of the human
      colon carcinoma cell line Caco-2. Growth of Caco-2 and HCT-116 cells was analyzed
      by crystal violet assay, which demonstrated dose- and time-dependent decreases in
      cell numbers. Treatment of Caco-2 cells with piceatannol reduced proliferation
      rate. No effect on differentiation was observed. Determination of cell cycle
      distribution by flow cytometry revealed an accumulation of cells in the S phase.
      Immunoblotting demonstrated that cyclin-dependent kinases (cdk) 2 and 6, as well
      as cdc2 were expressed at steady-state levels, whereas cyclin D1, cyclin B1 and
      cdk 4 were downregulated. The abundance of p27(Kip1) was also reduced, whereas
      the protein level of cyclin E was enhanced. Cyclin A levels were enhanced only at
      concentrations up to 100 micromol/L. These changes also were observed in studies
      with HCT-116 cells. On the basis of our findings, piceatannol can be considered
      to be a promising chemopreventive or anticancer agent.

PMID- 11823595
TI  - Serum levels of micronutrients, antioxidants and total antioxidant status predict
      risk of breast cancer in a case control study.
AB  - We performed a case control study to assess the association between serum
      micronutrient and antioxidant levels and the risk of breast cancer. Newly
      diagnosed breast cancer cases were recruited before any treatment and matched
      with controls randomly selected from the electoral roll. Blood samples were
      collected from 153 breast cancer cases and 151 controls. Serum samples were
      analyzed for retinol, alpha-tocopherol, lycopene, alpha- and beta-carotene by
      HPLC, and total antioxidant status by the Trolox-equivalent antioxidant assay.
      Serum albumin, bilirubin and uric acid levels were also determined. After
      adjustment for age at menarche, parity, dietary fat and alcohol intake, we
      observed the following reductions in odds ratios for breast cancer risk comparing
      the highest with the lowest quartiles: 0.47 [95% confidence interval (CI) 0.24,
      0.91] for beta-carotene; 0.53 (CI 0.28, 1.01) for retinol; 0.50 (CI 0.26, 0.97)
      for bilirubin and 0.47 (CI 0.24, 0.94) for total antioxidant status. We conclude
      that increased serum levels of beta-carotene, retinol, bilirubin and total
      antioxidant status are associated with reductions in breast cancer risk.

PMID- 11823596
TI  - Selenium-enriched broccoli decreases intestinal tumorigenesis in multiple
      intestinal neoplasia mice.
AB  - Multiple intestinal neoplasia (Min) mice are a good model for the investigation
      of the effects of dietary alterations in a genetic model for intestinal cancer.
      Previous studies have shown that selenium-enriched broccoli is protective against
      chemically induced colon cancer susceptibility. This study investigated whether
      selenium-enriched broccoli would be protective against intestinal cancer
      susceptibility in Min mice. Five-week-old heterozygotic male Min mice were fed an
      AIN-93-based diet containing either low-selenium broccoli or an equivalent amount
      of high-selenium broccoli for 10 wk. Mice fed the selenium-enriched broccoli had
      fewer (P < 0.02) small intestinal (46.4 +/- 3.7 vs. 65.6 +/- 6.1) and large
      intestinal (0.43 +/- 0.17 vs. 1.93 +/- 0.27) tumors than those fed an equivalent
      amount of unenriched broccoli. Min mice fed the selenium-enriched broccoli had
      small but significant (P < 0.0001) increases in plasma and liver selenium
      concentrations and red blood cell glutathione peroxidase activity. These results
      extend previous observations that selenium-enriched broccoli is protective
      against chemically induced mammary and colon cancer in rats.

PMID- 11823597
TI  - Field methods for body composition assessment are valid in healthy chinese
      adults.
AB  - There is little information on the accuracy of simple body composition methods in
      non-Western populations. We determined the percentage of body fat (%BF) by
      isotope dilution [oxygen-18 (H(2)(18)O) and deuterium oxide ((2)H(2)O)] and
      anthropometry in 71 healthy, urban Chinese adults aged 35-49 y [body mass index
      (BMI) 18-35 kg/m(2)]. The accuracy of several prediction equations for assessment
      of %BF from skinfold measurements was evaluated against %BF determined by
      H(2)(18)O dilution. We also assessed the relationship between BMI and %BF, and
      the fat-free mass (FFM) hydration coefficient for our population. All skinfold
      equations yielded means within approximately 2%BF of H(2)(18)O-derived %BF.
      However, on the basis of residual plot analysis and the 95% confidence interval
      (CI) for the mean difference between methods, the equations of Durnin and
      Womersley (for assessment of body density from skinfolds) coupled with that of
      Brozek et al. (for assessment of %BF from body density) provided the most valid
      assessment for individuals. In addition, the FFM hydration coefficient averaged
      0.734 +/- 0.002 (SEM), indicating that the usually assumed value of 0.732 is
      appropriate for this population. Finally, although BMI had high specificity (90%)
      for classifying individuals as having body fat within the normal range (<24%BF
      for men, and <35%BF for women), it had poor sensitivity (66%) for identifying
      individuals as having high body fat. We conclude that compared with H(2)(18)O
      dilution, skinfold thickness can provide an accurate and reliable assessment of
      body composition in healthy Chinese adults. Furthermore, using the equation of
      Brozek et al. may be preferable to using Siri's equation to predict %BF from body
      density in populations in which individuals have >30%BF.

PMID- 11823598
TI  - Rapid and simple measurement of retinol in human dried whole blood spots.
AB  - We describe an improved method for the measurement of retinol in dried blood
      spots (DBS) on filter paper. Retinol in human DBS on filter paper was analyzed by
      normal phase HPLC after a simple extraction method. Retinol associated with its
      binding protein was eluted from the paper into aqueous solution facilitated by
      ultrasonic agitation. Retinol associated with retinol binding protein was
      denatured with acetonitrile, and then retinol was isolated in a single hexane
      extract and analyzed directly by HPLC. When analyzing DBS, the individual plasma
      volume of the spots was calculated by measuring the sodium content or by weighing
      the blood spots. The described method yielded low intra- and interassay
      variability (<6%), with sufficient sensitivity (detection limit, 0.1 micromol/L)
      and good recovery (97% spike). Compared with matching plasma samples, DBS retinol
      consistently decreased 18-23% during the 1st wk of storage. After 1 wk, retinol
      remained stable in the blood spots at 23 degrees C for >3 mo. In conclusion, the
      analysis of retinol in DBS by HPLC is comparable to retinol analysis in serum.
      The variability of the method was reduced by using sodium concentration to
      estimate sample volume. Collection of DBS for retinol analysis is appropriate
      under field conditions, where it is difficult to centrifuge or freeze blood
      samples.

PMID- 11823599
TI  - Accuracy of simple techniques for estimating fractional zinc absorption in
      humans.

PMID- 11823601
TI  - Mechanisms involved in the intestinal digestion and absorption of dietary vitamin
      A.

PMID- 11823604
TI  - Instability of glacial climate in a model of the ocean- atmosphere-cryosphere
      system.
AB  - In contrast to the relatively stable climate of the past 10,000 years, during
      glacial times the North Atlantic region experienced large-amplitude transitions
      between cold (stadial) and warm (interstadial) states. In this modeling study, we
      demonstrate that hydrological interactions between the Atlantic thermohaline
      circulation (THC) and adjacent continental ice sheets can trigger abrupt warming
      events and also limit the lifetime of the interstadial circulation mode. These
      interactions have the potential to destabilize the THC, which is already more
      sensitive for glacial conditions than for the present-day climate, thus providing
      an explanation for the increased variability of glacial climate.

PMID- 11823605
TI  - Constraints in the evolution of sex ratio adjustment.
AB  - When the relative fitness of male and female offspring varies with environmental
      conditions, evolutionary theory predicts that parents should adjust the sex of
      their offspring accordingly. Qualitative and even quantitative support for this
      prediction is striking in some taxa but much less convincing in others.
      Explaining such variation across taxa in the fit of sex ratio theory remains a
      major challenge. We use meta-analysis to test the role of two constraints in the
      evolution of sex ratios. Based on analysis of sex ratio skews in birds and wasps,
      we show that (i) mechanisms of sex determination do not necessarily constrain the
      evolution of sex ratio adjustment, and (ii) parental ability to predict their
      offsprings' environment influences the evolution of sex ratio patterns across
      taxa. More generally, our results show that multiple constraints may determine
      the precision of adaptation.

PMID- 11823607
TI  - Good prediction, bad news.

PMID- 11823608
TI  - Ballistic missile defense. Sensor failure in 1997 test sparks new controversy.

PMID- 11823606
TI  - Loss of sex discrimination and male-male aggression in mice deficient for TRP2.
AB  - The mouse vomeronasal organ (VNO) is thought to mediate social behaviors and
      neuroendocrine changes elicited by pheromonal cues. The molecular mechanisms
      underlying the sensory response to pheromones and the behavioral repertoire
      induced through the VNO are not fully characterized. Using the tools of mouse
      genetics and multielectrode recording, we demonstrate that the sensory activation
      of VNO neurons requires TRP2, a putative ion channel of the transient receptor
      potential family that is expressed exclusively in these neurons. Moreover, we
      show that male mice deficient in TRP2 expression fail to display male-male
      aggression, and they initiate sexual and courtship behaviors toward both males
      and females. Our study suggests that, in the mouse, sensory activation of the VNO
      is essential for sex discrimination of conspecifics and thus ensures gender
      specific behavior.

PMID- 11823609
TI  - Anthrax. 'Borrowed immunity' may save future victims.

PMID- 11823610
TI  - Nuclear waste. 'Hot' legacy raises alarm in the Caucasus.

PMID- 11823611
TI  - Stem cell research. Primate parthenotes yield stem cells.

PMID- 11823612
TI  - Cell biology. Molecular motors move in mysterious ways.

PMID- 11823613
TI  - Spanish universities. Reforms spark more jobs--and protests.

PMID- 11823614
TI  - Pheromone reception. When in doubt, mice mate rather than hate.

PMID- 11823615
TI  - Myanmar. Planned reactor ruffles global feathers.

PMID- 11823616
TI  - U.S. Supreme Court. Census case tests statistical method.

PMID- 11823617
TI  - High-energy physics. Report backs collider and an expanded field.

PMID- 11823618
TI  - 2003 budget: Bioterrorism drives record NIH request.

PMID- 11823620
TI  - Superconductors. YBCO confronts life in the slow lane.

PMID- 11823619
TI  - Superconductors. MgB2 trades performance for a shot at the real world.

PMID- 11823621
TI  - Canada. New money widens gap among universities.

PMID- 11823622
TI  - Mathematics in film. Beautiful Mind's math guru makes truth = beauty.

PMID- 11823623
TI  - BSE in sheep? Humiliated lab fights to save face.

PMID- 11823624
TI  - Portraits of science. Logic, learning, and experimental medicine.

PMID- 11823625
TI  - Cosmology. The saga of 3He.

PMID- 11823626
TI  - Biomedicine. A cargo receptor mystery APParently solved?

PMID- 11823627
TI  - Transcription. Oxygen sensing gets a second wind.

PMID- 11823628
TI  - Neurobiology. Chaperones take flight.

PMID- 11823629
TI  - Applied physics. Ultrasmall wires get excited.

PMID- 11823630
TI  - Climate change. Tropical surprises.

PMID- 11823631
TI  - Signal transduction and the control of gene expression.
AB  - More than 2000 transcription factors are encoded in the human genome. Such
      proteins have often been classified according to common structural elements. But
      because transcription factors evolved in the service of biologic function, we
      propose an alternative grouping of eukaryotic transcription factors on the basis
      of characteristics that describe their roles within cellular regulatory circuits.

PMID- 11823632
TI  - Parthenogenetic stem cells in nonhuman primates.

PMID- 11823634
TI  - Tunneling spectroscopy of the elementary excitations in a one-dimensional wire.
AB  - The collective excitation spectrum of interacting electrons in one dimension has
      been measured by controlling the energy and momentum of electrons tunneling
      between two closely spaced, parallel quantum wires in a GaAs/AlGaAs
      heterostructure while measuring the resulting conductance. The excitation
      spectrum deviates from the noninteracting spectrum, attesting to the importance
      of Coulomb interactions. An observed 30% enhancement of the excitation velocity
      relative to noninteracting electrons with the same density, a parameter
      determined experimentally, is consistent with theories on interacting electrons
      in one dimension. In short wires, 6 and 2 micrometers long, finite size effects,
      resulting from the breaking of translational invariance, are observed.

PMID- 11823633
TI  - Regulation of organogenesis by the Caenorhabditis elegans FoxA protein PHA-4.
AB  - The pha-4 locus encodes a forkhead box A (FoxA/HNF3) transcription factor homolog
      that specifies organ identity for Caenorhabditis elegans pharyngeal cells. We
      used microarrays to identify pharyngeal genes and analyzed those genes to
      determine which were direct PHA-4 targets. Our data suggest that PHA-4 directly
      activates most or all pharyngeal genes. Furthermore, the relative affinity of PHA
      4 for different TRTTKRY (R = A/G, K = T/G, Y = T/C) elements modulates the onset
      of gene expression, providing a mechanism to activate pharyngeal genes at
      different developmental stages. We suggest that direct transcriptional regulation
      of entire gene networks may be a common feature of organ identity genes.

PMID- 11823635
TI  - A carbon-free sandwich complex [(P5)2Ti]2-.
AB  - Reactions of highly reduced titanium complexes with white phosphorus, P4, at or
      below 25 degrees C yielded brown to deep red-brown salts of the first entirely
      inorganic metallocene, [(eta5-P5)2Ti](2-)(1). Like ferrocene and other carbon
      based metallocenes, the structure of 1 has parallel and planar five-membered
      rings symmetrically positioned about the central metal atom. Despite its electron
      deficient (16 electron) and formally zerovalent titanium character, salts of 1
      are highly stable toward heat and air, both in solution and in the solid state.
      Computational studies show that the pentaphosphacyclopentadienyl unit, P5,
      functions as an unusually effective acceptor ligand, and this results in
      substantial stabilization of 1.

PMID- 11823636
TI  - Aerosol effect on cloud droplet size monitored from satellite.
AB  - Aerosol concentration and cloud droplet radii derived from space-borne
      measurements are used to explore the effect of aerosols on cloud microphysics.
      Cloud droplet size is found to be largest (14 micrometers) over remote tropical
      oceans and smallest (6 micrometers) over highly polluted continental areas. Small
      droplets are also present in clouds downwind of continents. By using estimates of
      droplet radii coupled with aerosol load, a statistical mean relationship is
      derived. The cloud droplet size appears to be better correlated with an aerosol
      index that is representative of the aerosol column number under some assumptions
      than with the aerosol optical thickness. This study reveals that the effect of
      aerosols on cloud microphysics is significant and occurs on a global scale.

PMID- 11823637
TI  - Evidence for strengthening of the tropical general circulation in the 1990s.
AB  - Satellite observations suggest that the thermal radiation emitted by Earth to
      space increased by more than 5 watts per square meter, while reflected sunlight
      decreased by less than 2 watts per square meter, in the tropics over the period
      1985-2000, with most of the increase occurring after 1990. By analyzing temporal
      changes in the frequency of occurrence of emitted thermal and reflected solar
      fluxes, the effects of El Nino-Southern Oscillation are minimized, and an
      independent longer-time-scale variation of the radiation budget is identified.
      Similar analyses of upper tropospheric humidity, cloud amount, surface air
      temperature, and vertical velocity confirm that these flux changes are associated
      with a decadal-time-scale strengthening of the tropical Hadley and Walker
      circulations. Equatorial convective regions have intensified in upward motion and
      moistened, while both the equatorial and subtropical subsidence regions have
      become drier and less cloudy.

PMID- 11823638
TI  - Evidence for large decadal variability in the tropical mean radiative energy
      budget.
AB  - It is widely assumed that variations in Earth's radiative energy budget at large
      time and space scales are small. We present new evidence from a compilation of
      over two decades of accurate satellite data that the top-of-atmosphere (TOA)
      tropical radiative energy budget is much more dynamic and variable than
      previously thought. Results indicate that the radiation budget changes are caused
      by changes in tropical mean cloudiness. The results of several current climate
      model simulations fail to predict this large observed variation in tropical
      energy budget. The missing variability in the models highlights the critical need
      to improve cloud modeling in the tropics so that prediction of tropical climate
      on interannual and decadal time scales can be improved.

PMID- 11823639
TI  - Distinguishing inchworm and hand-over-hand processive kinesin movement by neck
      rotation measurements.
AB  - The motor enzyme kinesin makes hundreds of unidirectional 8-nanometer steps
      without detaching from or freely sliding along the microtubule on which it moves.
      We investigated the kinesin stepping mechanism by immobilizing a Drosophila
      kinesin derivative through the carboxyl-terminal end of the neck coiled-coil
      domain and measuring orientations of microtubules moved by single enzyme
      molecules at submicromolar adenosine triphosphate concentrations. The kinesin
      mediated microtubule-surface linkage was sufficiently torsionally stiff (>/=2.0
      +/- 0.9 x 10(-20) Newton meters per radian2) that stepping by the hypothesized
      symmetric hand-over-hand mechanism would produce 180 degree rotations of the
      microtubule relative to the immobilized kinesin neck. In fact, there were no
      rotations, a finding that is inconsistent with symmetric hand-over-hand movement.
      An alternative "inchworm" mechanism is consistent with our experimental results.

PMID- 11823640
TI  - Partitioning of the matrix fraction of the Golgi apparatus during mitosis in
      animal cells.
AB  - The Golgi apparatus is partitioned during mitosis in animal cells by a process of
      fragmentation, dispersal, and reassembly in each daughter cell. We fractionated
      the Golgi apparatus in vivo using the drug brefeldin A or a dominant-negative
      mutant of the Sar1p protein. After these treatments, Golgi enzymes moved back to
      the endoplasmic reticulum, leaving behind a matrix of Golgi structural proteins.
      Under these conditions, cells still entered and exited mitosis normally, and
      their Golgi matrix partitioned in a manner very similar to that of the complete
      organelle. Thus, the matrix may be the partitioning unit of the Golgi apparatus
      and may carry the Golgi enzyme-containing membranes into the daughter cells.

PMID- 11823641
TI  - Role of Escherichia coli curli operons in directing amyloid fiber formation.
AB  - Amyloid is associated with debilitating human ailments including Alzheimer's and
      prion diseases. Biochemical, biophysical, and imaging analyses revealed that
      fibers produced by Escherichia coli called curli were amyloid. The CsgA curlin
      subunit, purified in the absence of the CsgB nucleator, adopted a soluble,
      unstructured form that upon prolonged incubation assembled into fibers that were
      indistinguishable from curli. In vivo, curli biogenesis was dependent on the
      nucleation-precipitation machinery requiring the CsgE and CsgF chaperone-like and
      nucleator proteins, respectively. Unlike eukaryotic amyloid formation, curli
      biogenesis is a productive pathway requiring a specific assembly machinery.

PMID- 11823642
TI  - A role for interaction of the RNA polymerase flap domain with the sigma subunit
      in promoter recognition.
AB  - In bacteria, promoter recognition depends on the RNA polymerase sigma subunit,
      which combines with the catalytically proficient RNA polymerase core to form the
      holoenzyme. The major class of bacterial promoters is defined by two conserved
      elements (the -10 and -35 elements, which are 10 and 35 nucleotides upstream of
      the initiation point, respectively) that are contacted by sigma in the
      holoenzyme. We show that recognition of promoters of this class depends on the
      "flexible flap" domain of the RNA polymerase beta subunit. The flap interacts
      with conserved region 4 of sigma and triggers a conformational change that moves
      region 4 into the correct position for interaction with the -35 element. Because
      the flexible flap is evolutionarily conserved, this domain may facilitate
      promoter recognition by specificity factors in eukaryotes as well.

PMID- 11823643
TI  - Asparagine hydroxylation of the HIF transactivation domain a hypoxic switch.
AB  - The hypoxia-inducible factors (HIFs) 1alpha and 2alpha are key mammalian
      transcription factors that exhibit dramatic increases in both protein stability
      and intrinsic transcriptional potency during low-oxygen stress. This increased
      stability is due to the absence of proline hydroxylation, which in normoxia
      promotes binding of HIF to the von Hippel-Lindau (VHL tumor suppressor) ubiquitin
      ligase. We now show that hypoxic induction of the COOH-terminal transactivation
      domain (CAD) of HIF occurs through abrogation of hydroxylation of a conserved
      asparagine in the CAD. Inhibitors of Fe(II)- and 2-oxoglutarate-dependent
      dioxygenases prevented hydroxylation of the Asn, thus allowing the CAD to
      interact with the p300 transcription coactivator. Replacement of the conserved
      Asn by Ala resulted in constitutive p300 interaction and strong transcriptional
      activity. Full induction of HIF-1alpha and -2alpha, therefore, relies on the
      abrogation of both Pro and Asn hydroxylation, which during normoxia occur at the
      degradation and COOH-terminal transactivation domains, respectively.

PMID- 11823644
TI  - Dynamics of depolarization and hyperpolarization in the frontal cortex and
      saccade goal.
AB  - The frontal eye field and neighboring area 8Ar of the primate cortex are involved
      in programming and execution of saccades. Electrical microstimulation in these
      regions elicits short-latency contralateral saccades. To determine how
      spatiotemporal dynamics of microstimulation-evoked activity are converted into
      saccade plans, we used a combination of real-time optical imaging and
      microstimulation in behaving monkeys. Short stimulation trains evoked a rapid and
      widespread wave of depolarization followed by unexpected large and prolonged
      hyperpolarization. During this hyperpolarization saccades are almost exclusively
      ipsilateral, suggesting an important role for hyperpolarization in determining
      saccade goal.

PMID- 11823645
TI  - Chaperone suppression of alpha-synuclein toxicity in a Drosophila model for
      Parkinson's disease.
AB  - Parkinson's disease is a movement disorder characterized by degeneration of
      dopaminergic neurons in the substantia nigra pars compacta. Dopaminergic neuronal
      loss also occurs in Drosophila melanogaster upon directed expression of alpha
      synuclein, a protein implicated in the pathogenesis of Parkinson's disease and a
      major component of proteinaceous Lewy bodies. We report that directed expression
      of the molecular chaperone Hsp70 prevented dopaminergic neuronal loss associated
      with alpha-synuclein in Drosophila and that interference with endogenous
      chaperone activity accelerated alpha-synuclein toxicity. Furthermore, Lewy bodies
      in human postmortem tissue immunostained for molecular chaperones, also
      suggesting that chaperones may play a role in Parkinson's disease progression.

PMID- 11823646
TI  - In situ beta radiation to prevent recanalization after coil embolization of
      cerebral aneurysms.
AB  - BACKGROUND AND PURPOSE: Endovascular treatment of cerebral aneurysms, a minimally
      invasive alternative to surgery, is too often followed by recanalization and
      recurrences. The purpose of this work was to assess if in situ beta radiation can
      inhibit recanalization after coil embolization. METHODS: Radioactive platinum
      coils (32P-coils) were produced by ion implantation of 32P. A single-coil
      arterial occlusion model was used to compare angiographic and pathological
      results at 1 to 12 weeks after nonradioactive and 32P-coil embolization of
      maxillary, cervical, and vertebral arteries in 26 dogs. Coils of varying
      activities were used and results compared to define the minimal activity required
      to inhibit recanalization. Similar experiments were performed in 16 porcine
      maxillary and lingual and 8 rabbit axillary arteries. Results of 32P-coil
      embolization of bifurcation aneurysms were then compared with embolization with
      nonradioactive coils in 12 dogs at 3 months. RESULTS: Nonradioactive coil
      embolization of canine arteries led to occlusion at 1 week, followed by
      recanalization at 2 weeks, which persisted at 3 months in all cases. 32P-coils,
      ion-implanted with activities above 0.13 microCi/cm, led to persistent occlusion
      at 3 months in 80% of arteries. 32P-coils ion-implanted with the same activity
      inhibited recanalization in porcine and rabbit arteries. Bifurcation aneurysms
      treated with 32P-coils had better angiographic results at 3 months (P=0.006) than
      aneurysms treated with nonradioactive coils. Arteries occluded were filled with
      fibrous tissue at 3 months. Aneurysms embolized with 32P-coils showed more
      complete neointimal coverage of the neck, without recanalization, as compared
      with aneurysms treated with nonradioactive coils. CONCLUSION: In situ low-dose
      beta radiation inhibits recanalization after coil embolization and may improve
      long-term results of endovascular treatment of aneurysms.

PMID- 11823647
TI  - Cerebral blood flow restoration and reperfusion injury after ultraviolet laser
      facilitated middle cerebral artery recanalization in rat thrombotic stroke.
AB  - BACKGROUND AND PURPOSE: A reversible model of focal thrombotic stroke was
      developed in the rat and examined for histological evidence of reperfusion injury
      after clinically relevant times of recanalization. METHODS: The distal middle
      cerebral artery of 28 male Sprague-Dawley rats was occluded by 562-nm laser
      driven photothrombosis for 0.5, 2, and 3 hours or permanently (each n=7) and was
      recanalized by 355-nm UV laser irradiation. Occlusive material was examined by
      transmission electron microscopy. Cortical cerebral blood flow was monitored by
      laser-Doppler flowmetry. Brain infarcts were examined histologically at 3 days.
      RESULTS: After occlusion, cortical cerebral blood flow was reduced to 33+/-4% of
      baseline for all groups and was restored to 82+/-9%, 75+/-3%, and 93+/-7% of
      baseline for the 0.5-, 2-, and 3-hour groups, respectively, following
      recanalization after 29+/-8, 38+/-20, and 70+/-33 minutes of UV laser
      irradiation. The thrombotic occlusion contained compactly aggregated platelets
      but no fibrin, with length (1.2 to 1.8 mm) proportional to the ischemic period.
      During recanalization, microchannels containing erythrocytes and scattered
      leukocytes and bordered by intact disaggregated platelets infiltrated the
      thrombus. Infarct volumes (mm3) at 3 days were 12+/-3 for the permanent case and
      8+/-4, 24+/-3, and 30+/-9 for the 0.5-, 2-, and 3-hour cases, respectively, thus
      demonstrating reperfusion injury histologically in the latter 2 groups. No
      hemorrhage was seen. CONCLUSIONS: UV laser-facilitated dissolution of a
      conventionally refractory platelet thrombus provides a novel and effective method
      for restoring blood flow without hemorrhagic complications during thrombotic
      stroke. This was the first observation of histologically confirmed reperfusion
      injury in such a model.

PMID- 11823648
TI  - Cost of identifying patients for carotid endarterectomy.
AB  - BACKGROUND AND PURPOSE: The cost of carotid endarterectomy (CEA) usually
      considers only the cost of the preoperative investigations and the procedure for
      the individual patient but ignores the cost incurred in selecting a patient from
      a referred "pool" of potential candidates or the "total direct program cost." The
      aim of this study was to estimate the total direct program cost (workup and
      procedure) of CEA in a large major teaching hospital in Edinburgh, Scotland using
      a retrospective study design. METHODS: Participants were patients with transient
      ischemic attacks and mild strokes referred to the neurovascular clinics for
      assessment, investigation, and possible CEA. The "workup" was defined as the
      clinical consultation, carotid duplex, 1 follow-up visit, and a catheter
      angiogram where indicated. We used data routinely collected from the
      neurovascular clinics during a 1-year period to estimate the workup cost of
      patients who might be suitable for CEA. The CEA procedure cost was estimated
      prospectively in a concurrent study. Estimated costs were applied to the
      proportions assessed at the different levels of investigation to determine the
      total direct program cost of CEA. RESULTS: A total of 790 new patients with
      symptoms suggestive of transient ischemic attacks and mild strokes were
      identified. Four hundred one (51%) patients were referred for carotid duplex.
      Duplex identified 78 (10%) with carotid stenosis of > or =70%. Of the total of
      790 patients, 26 (3.3%) had catheter angiogram and 18 (2.3%) had CEA. The total
      direct program cost to investigate this cohort was about 207 000 pounds sterling,
      with 68% (140 000 pounds sterling) of the cost incurred before any surgery was
      performed. CONCLUSION: The cost of identifying suitable patients for carotid
      surgery is quite high, with more than 30% of the cost attributed to the initial
      consultation at the neurovascular clinics. The cost of preventing 1 stroke by CEA
      is in the region of 100 000 pounds sterling at 1997/1998 prices if all the costs
      incurred in the workup of a cohort for potential CEA are included.

PMID- 11823649
TI  - Quality of life, anxiety, and depression in patients with an untreated
      intracranial aneurysm or arteriovenous malformation.
AB  - BACKGROUND AND PURPOSE: The objective of this study was to assess the health
      related quality of life and symptoms of anxiety and depression in patients who
      are aware of the presence of a patent aneurysm or arteriovenous malformation.
      METHODS: Participants were retrospectively identified and invited to participate
      in the study; consenting participants were interviewed in a face-to-face setting
      by means of 2 questionnaires assessing health-related quality of life (Sickness
      Impact Profile [SIP] and the MOS Short Form-36 [SF-36]) and psychological state
      (Hospital Anxiety and Depression Scale [HADS]). We used Student's t test
      statistics to compare the scores of the study population with the scores of
      reference populations. RESULTS: We identified 21 patients, of whom 9 had an
      aneurysm and 12 had an arteriovenous malformation. Compared with the reference
      population, these patients had a reduced quality of life for sleep and rest
      (difference of SIP means, 6.8; 95% CI, 3.1 to 10.5), emotional behavior (10.1;
      95% CI, 5.7 to 14.6), mobility (5.4; 95% CI, 2.1 to 8.7), social interactions
      (5.3; 95% CI, 1.6 to 8.9), and alertness behavior (11.9; 95% CI, 6.2 to 17.5).
      The SIP psychosocial subscore (7.1; 95% CI, 3.9 to 10.2) and total SIP score
      (4.7; 95% CI, 2.2 to 7.2) were also significantly impaired. For the SF-36
      domains, social functioning was significantly decreased compared with the
      reference population (8.9; 95% CI, 0.1 to 17.7). HADS scores for depression were
      similar for patients and the reference population. CONCLUSIONS: Our study shows
      that knowledge of harboring an unoccluded untreated intracranial aneurysm or
      arteriovenous malformation reduces quality of life, most prominently on the
      psychosocial domains, without leading to substantially raised levels of anxiety
      and depression.

PMID- 11823650
TI  - The concept of patient motivation: a qualitative analysis of stroke
      professionals' attitudes.
AB  - BACKGROUND AND PURPOSE: The purpose of this work was to investigate how stroke
      rehabilitation professionals understand the concept of motivation and the ways
      that they use this concept in their clinical practice. METHODS: This qualitative
      study used semistructured, in-depth interviews with the professionals working in
      the stroke unit of an inner-city teaching hospital in the UK. RESULTS: Motivation
      was a frequently used concept and was described as an important determinant of
      rehabilitation outcome. Motivation was attributed to patients on the basis of
      their demeanor (proactivity was equated with motivation, passivity with lack of
      motivation) and their compliance with rehabilitation (compliance was seen as
      indicative of motivation, noncompliance as a lack of motivation). These criteria
      were found to have blurred boundaries. The determinants of motivation were
      located partly in personality factors but also in social factors. Central among
      the social factors were aspects of the professionals' own behavior taken to
      positively and negatively affect motivation. Some professionals reported treating
      unmotivated patients differently from motivated ones, especially if these
      unmotivated patients were elderly. Motivation was described as a potentially
      dangerous label. CONCLUSIONS: Professionals are wary of the concept of motivation
      yet commonly use it in their clinical practice. The blurred boundaries of the
      criteria used to identify motivation mean that patients must strike a delicate
      balance between proactivity and compliance to avoid being categorized as
      unmotivated. The way the concept of motivation is used in clinical practice might
      have negative implications for patient care, eg, when reticent yet motivated
      patients are labeled unmotivated.

PMID- 11823651
TI  - Randomized controlled study of stroke unit care versus stroke team care in
      different stroke subtypes.
AB  - BACKGROUND AND PURPOSE: The benefits of stroke unit management may vary according
      to stroke subtype. A post hoc analysis of the influence of stroke subtype on
      stroke unit effectiveness was undertaken by using prospective data collected in a
      randomized controlled trial. METHODS: Two hundred sixty-seven patients with
      moderately severe ischemic stroke (164 with large-vessel infarcts and 103 with
      lacunar infarcts) were randomly allocated to treatment in stroke units or in
      general medical wards with specialist stroke team support. Mortality,
      institutionalization, neurological, functional, and quality-of-life scores and
      resource use were assessed at 3 and again at 12 months after stroke onset. An
      intention-to-treat analysis was undertaken, and logistic regression was used to
      evaluate the independent effect of stroke unit intervention. RESULTS: Stroke team
      supported management was associated with higher mortality (odds ratio [OR] 4.9,
      95% CI 1.3 to 18.6) and higher mortality or institutionalization (OR 2.9, 95% CI
      1.1 to 7.4) at 3 months (OR 3.6, 95% CI 1.5 to 8.7) and at 1 year (OR 2.8, 95% CI
      1.3 to 6.2) in patients with large-vessel infarcts. In contrast, there were no
      significant differences in outcome in patients with lacunar strokes managed in
      the stroke unit or by the stroke team. In patients with lacunar strokes, stroke
      unit care was associated with a longer length of hospital stay (18 versus 13.5
      days for stroke unit care versus stroke team care, respectively; P<0.01) and
      significantly greater use of therapy. CONCLUSIONS: Stroke units improve the
      outcome in patients with large-vessel infarcts but not in those with lacunar
      syndromes. For lacunar strokes, stroke unit management may be associated with
      higher initial health costs for equivalent benefit.

PMID- 11823652
TI  - Cerebral protection during carotid artery stenting: collection and
      histopathologic analysis of embolized debris.
AB  - BACKGROUND AND PURPOSE: Histopathologic analysis was performed to better
      understand quantity, particle size, and composition of embolized debris collected
      in protection filters during carotid artery stent implantation. METHODS: Elective
      carotid stent implantation with the use of a distal filter protection was
      attempted in 38 consecutive lesions (36 patients) of the internal carotid artery
      presenting >70% diameter stenosis (mean, 82.1+/-11.1%). Mean age of the patients
      was 70.7+/-7.7 years; 75% were men, and 50% of patients had previous neurological
      symptoms. RESULTS: In 37 lesions (97.4%) it was possible to position the filter
      device, and in all lesions a stent was successfully implanted. The only
      complication occurring in the hospital and during the 30-day follow-up was 1
      death due to acute myocardial infarction. Neurological sequelae did not occur.
      Histomorphometric analysis was performed on the filters. Presence of debris was
      detected in 83.7% of filters. The mean surface area of the polyurethane membrane
      filter covered with material was 53.2+/-19.8%. Particle size ranged from 1.08 to
      5043.5 microm (mean, 289.5+/-512 microm) in the major axis and 0.7 to 1175.3
      microm (mean, 119.7+/-186.7 microm) in the minor axis. Collected debris consisted
      predominantly of thrombotic material, foam cells, and cholesterol clefts.
      CONCLUSIONS: By the use of distal protection filters during carotid artery
      stenting, it was possible to collect particulate debris potentially leading to
      distal vessel occlusion in a high percentage of cases. Qualitative analysis of
      embolized material showed debris dislocated during the percutaneous intervention
      from atheromatous plaques.

PMID- 11823653
TI  - Stroke is associated with coronary calcification as detected by electron-beam CT:
      the Rotterdam Coronary Calcification Study.
AB  - BACKGROUND AND PURPOSE: Coronary calcification as detected by electron-beam CT
      measures the atherosclerotic plaque burden and has been reported to predict
      coronary events. Because atherosclerosis is a generalized process, coronary
      calcification may also be associated with manifest atherosclerotic disease at
      other sites of the vascular tree. We examined whether coronary calcification as
      detected by electron-beam CT is related to the presence of stroke. METHODS: From
      1997 onward, subjects were invited to participate in the prospective Rotterdam
      Coronary Calcification Study and undergo electron-beam CT to detect coronary
      calcification. The study was embedded in the population-based Rotterdam Study.
      Calcifications were quantified in a calcium score according to Agatston's method.
      Calcium scores were available for 2013 subjects (mean age [SD], 71 [5.7] years).
      Fifty subjects had experienced stroke before scanning. RESULTS: Subjects were 2
      times more likely to have experienced stroke when their calcium score was between
      101 and 500 (odds ratio [OR], 2.1; 95% CI, 0.9 to 4.7) and 3 times more likely
      when their calcium score was above 500 (OR, 3.3; 95% CI, 1.5 to 7.2), compared
      with subjects in the lowest calcium score category (0 to 100). Additional
      adjustment for cardiovascular risk factors did not materially alter the risk
      estimates. CONCLUSIONS: In this population-based study, a markedly graded
      association was found between coronary calcification and stroke. The results
      suggest that coronary calcification as detected by electron-beam CT may be useful
      to identify subjects at high risk of stroke.

PMID- 11823654
TI  - Combined clinical and imaging information as an early stroke outcome measure.
AB  - BACKGROUND AND PURPOSE: Imaging information has been proposed as a potential
      surrogate outcome in stroke clinical trials. The purpose of this study was to
      determine whether an early outcome measure combining clinical and imaging
      information is better than either alone in predicting 3-month outcome in acute
      ischemic stroke patients. METHODS: Clinical information (National Institutes of
      Health Stroke Scale) and imaging information (CT infarct volume), measured at 1
      week from 201 patients from the Randomized Trial of Tirilazad Mesylate in Acute
      Stroke (RANTTAS) study, were used in a multivariable logistic regression analysis
      to predict excellent and devastating 3-month outcome. The combined models were
      compared with the infarct volume models and the clinical models. Discrimination,
      calibration, and change in global model chi-square were assessed. RESULTS: The
      combined models and models using clinical information alone had areas under the
      receiver operating characteristic curves that did not differ significantly
      (probability value = 0.092 to 0.4), ranging from 0.83 to 0.95. The imaging alone
      models performed less well (P<0.005) and had areas under the receiver operating
      characteristic curves that ranged from 0.70 to 0.80. CONCLUSIONS: The National
      Institutes of Health Stroke Scale at 1 week is highly predictive of 3-month
      outcome in ischemic stroke patients. The addition of 1-week infarct volume does
      not improve the accuracy of the predictive model.

PMID- 11823655
TI  - Changes in plasma homocyst(e)ine in the acute phase after stroke.
AB  - BACKGROUND AND PURPOSE: Elevated plasma homocyst(e)ine [H(e)] concentration has
      been associated with an increased risk of stroke. Although the literature
      suggests that H(e) increases from the acute to the convalescent phase after a
      stroke, it is not known whether H(e) changes within the acute period. METHODS: A
      prospective, multicenter study was conducted to examine changes in H(e) during
      the 2 weeks after an incident stroke. Blood samples were collected at days 1, 3,
      5, 7, and between 10 and 14 days after the stroke. RESULTS: Seventy-six
      participants (51 men) were enrolled from 9 sites from February 1997 through June
      1998. Mean age was 65.6 years, and subjects had at least two H(e) measurements.
      The estimated mean H(e) level at baseline was 11.3+/-0.5 micromol/L, which
      increased consistently to a mean of 12.0+/-0.05, 12.4+/-0.5, 13.3+/-0.5, and
      13.7+/-0.7 micromol/L at days 3, 5, 7, and 10 to 14, respectively. The magnitude
      of the change in H(e) was not affected by age, sex, smoking status, alcohol use,
      history of hypertension or diabetes, or Rankin Scale Score. CONCLUSIONS: ; These
      data suggest that the clinical interpretation of H(e) after stroke and the
      eligibility for clinical trials assessing treatment for elevated H(e) levels
      require an adjustment in time since stroke to properly interpret the observed
      H(e) levels.

PMID- 11823656
TI  - Intracranial venous hemodynamics in patients with midline dislocation due to
      postischemic brain edema.
AB  - BACKGROUND AND PURPOSE: Cerebral venous pressure is governed by intracranial
      pressure, cerebral perfusion pressure, and venous outflow resistance. Therefore,
      changes in venous flow velocities are to be expected because of changes in
      intracranial pressure and brain tissue dislocation in patients with ischemic
      stroke and space-occupying brain edema. METHODS: In 21 prospectively recruited
      patients with middle cerebral artery stroke and postischemic edema, flow
      velocities in the basal veins, the vein of Galen, the straight sinus, and the P2
      segment of the posterior cerebral artery were recorded every 0.9+/-0.5 days
      during the first 5 days after symptom onset with the use of transcranial color
      coded duplex sonography. The midline shift of the third ventricle was determined
      by B-mode imaging. RESULTS: We observed an initial increase of flow velocity in
      the basal vein ipsilateral to the lesion, followed by a significant decrease
      within 5 days after symptom onset and with increasing midline shift in patients
      with brain herniation. In the straight sinus, flow velocity showed a biphasic U
      shaped response to increasing dislocation of the third ventricle, with an initial
      decrease followed by an increase in the course of mass movement (midline shift 1
      to 1.5 cm). A steep increase of flow velocity in the vein of Galen took place
      with a midline shift >1.5 cm. In the survivors these changes could not be
      observed. Flow velocity in the P2 segment of the posterior cerebral artery
      followed a typical course in neither the fatal cases nor the survivors.
      CONCLUSIONS: Monitoring of flow velocities in the basal cerebral veins and in the
      straight sinus can provide additional pathophysiological information in patients
      with space-occupying brain edema after acute stroke.

PMID- 11823657
TI  - Safety of intraventricular sodium nitroprusside and thiosulfate for the treatment
      of cerebral vasospasm in the intensive care unit setting.
AB  - BACKGROUND AND PURPOSE: We have recently reported the safety of intraventricular
      sodium nitroprusside for the treatment of cerebral ischemia from vasospasm.
      Treatments have been accompanied previously by cerebral angiography to gauge
      treatment effect on established vasospasm. We presently report the safe
      coadministration of intraventricular sodium nitroprusside and thiosulfate in 10
      patients with secured ruptured cerebral aneurysms in the intensive care unit,
      without the use of cerebral angiography for vasospasm treatment. METHODS:
      Patients were considered eligible for treatment on the basis of subarachnoid
      hemorrhage grade or manifestation of cerebral vasospasm by either transcranial
      Doppler ultrasonography (TCD) or neurological examination criteria. The route of
      administration was intraventricular, by way of ventriculostomy. Two separate
      protocols differing in dosage frequency were used, depending on the presence or
      absence of a new neurological deficit. Response to treatment was measured by TCD
      and neurological criteria. RESULTS: Good outcome was observed in 7 of 8 vasospasm
      patients presenting with clinical subarachnoid hemorrhage grade > or =3. Four
      patients demonstrated reversal of well-defined neurological deficits
      (hemiparesis, paraparesis) in the setting of treatment. Seven patients
      demonstrated a decrease in TCD velocities within 1 hour of treatment. Two
      patients died: 1 from intractable vasospasm despite maximal medical management
      and angioplasty and 1 from pulmonary causes. One episode of hypotension occurred
      in the setting of a high dose of medication. This responded promptly to medical
      management. Prolonged intracranial hypertension did not occur; modest elevations
      of both intracranial pressure and mean arterial blood pressure were observed when
      nausea and vomiting were associated with treatment, which occurred commonly in
      awake subjects. CONCLUSIONS: Intraventricular sodium nitroprusside with
      thiosulfate may be safely administered in the intensive care unit setting without
      the requirement of cerebral angiography to guide the effects of therapy.

PMID- 11823658
TI  - ATLANTIS trial: results for patients treated within 3 hours of stroke onset.
      Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke.
AB  - BACKGROUND AND PURPOSE: Only a single study has demonstrated beneficial effects
      of intravenous tissue plasminogen activator (tPA) in stroke patients. METHODS: We
      evaluated the clinical outcomes of the 61 patients enrolled in the Alteplase
      Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke (ATLANTIS)
      study who were randomized to receive intravenous tPA or placebo within 3 hours of
      symptom onset. RESULTS: Despite a significant increase in the rate of symptomatic
      intracranial hemorrhage, tPA-treated patients were more likely to have a very
      favorable outcome (score of < or = 1) on the National Institutes of Health Stroke
      Scale at 90 days (P=0.01). CONCLUSIONS: These data support current
      recommendations to administer intravenous tPA to eligible ischemic stroke
      patients who can be treated within 3 hours of symptom onset.

PMID- 11823659
TI  - Effects of body position on intracranial pressure and cerebral perfusion in
      patients with large hemispheric stroke.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to prospectively evaluate
      the effects of body position in patients with large supratentorial stroke.
      METHODS: We performed 43 monitoring sessions in 18 patients with acute complete
      or subtotal middle cerebral artery (MCA) territory stroke. Intracranial pressure
      (ICP) was monitored with a parenchymal probe. Mean arterial blood pressure, ICP,
      and MCA peak mean flow velocity (VmMCA) were continuously recorded. Patients with
      acute ICP crises were excluded. After baseline values at a 0 degree supine
      position were attained, the backrest was elevated in 2 steps of 5 minutes each to
      15 degrees and 30 degrees and then returned to 0 degree. RESULTS: Baseline mean
      arterial pressure was 90.0+/-1.6 mm Hg and fell to 82.7+/-1.7 mm Hg at 15 degrees
      and 76.1+/-1.6 mm Hg at 30 degrees backrest elevation (P<0.0001). ICP decreased
      from 13.0+/-0.9 to 12.0+/-0.9 mm Hg at 15 degrees and 11.4+/-0.9 mm Hg at 30
      degrees backrest elevation (P<0.0001). As a result, cerebral perfusion pressure
      decreased from a baseline value of 77.0+/-1.8 to 70.0+/-1.8 mm Hg at 15 degrees
      and 64.7+/-1.7 mm Hg at 30 degrees backrest elevation (P<0.0001). VmMCA was
      already higher on the affected side during baseline measurements. VmMCA decreased
      from 72.8+/-11.3 cm/s at 0 degree to 67.2+/-9.7 cm/s at 15 degrees and 61.2+/-8.9
      cm/s at 30 degrees on the affected and from 49.9+/-3.7 cm/s at 0 degree to 47.7+/
      3.6 cm/s at 15 degrees and 46.2+/-2.2 cm/s at 30 degrees on the contralateral
      side (P<0.0001). CONCLUSIONS: In patients with large hemispheric stroke without
      an acute ICP crisis, cerebral perfusion pressure was maximal in the horizontal
      position although ICP was usually at its highest point. If adequate cerebral
      perfusion pressure is considered more desirable than the absolute level of ICP,
      the horizontal position is optimal for these patients.

PMID- 11823660
TI  - Functional reorganization of motor cortex increases with greater axonal injury
      from CADASIL.
AB  - BACKGROUND AND PURPOSE: Cerebral autosomal dominant arteriopathy with subcortical
      infarcts and leukoencephalopathy (CADASIL) is an inherited small-artery disease
      that clinically involves only the brain. Particularly early in the disease,
      patients can show substantial or complete recovery after individual strokes.
      Cortical functional reorganization may contribute to limiting disability with
      such ischemic injury. We sought to test whether the extent of any functional
      changes in the motor cortex increases with greater brain axonal injury from
      CADASIL. METHODS: Functional MRI (fMRI) was used to characterize cortical
      activation during a simple hand-tapping task. Disease-associated pathology in
      subcortical white matter was assessed with the use of conventional fluid
      attenuated inversion recovery (FLAIR) MRI and MR spectroscopic imaging for
      measurement of N-acetyl aspartate decreases, a relatively specific measure of
      axonal injury. RESULTS: There was evidence for variable but substantial
      hyperintense white matter signal in all of the patients with FLAIR imaging. With
      the use of fMRI, the brain regions activated during motor tasks were similar for
      the 9 CADASIL patients and 7 controls, except that most (6 of 9) patients showed
      primary motor cortex activation both ipsilateral and contralateral to the hand
      moved, a finding in only 1 of 7 healthy controls. Ipsilateral motor cortex
      activation increased (r=-0.77, P<0.05) and motor cortex activation lateralization
      index decreased (r=0.68, P<0.02) with greater white matter injury (as assessed
      from decreases in the relative N-acetyl aspartate concentration) in a region of
      interest including descending motor fibers of the corticospinal pathway.
      CONCLUSIONS: The extent of functional reorganization of motor cortex increases
      with increasing axonal injury, consistent with an adaptive role for these
      changes. Increased functional recruitment of cortex ipsilateral to the limb moved
      therefore may contribute to limiting motor impairment from the subcortical injury
      of CADASIL.

PMID- 11823661
TI  - Prolonged cerebral transit time in CADASIL: a transcranial ultrasound study.
AB  - BACKGROUND AND PURPOSE: Cerebral autosomal dominant arteriopathy with subcortical
      infarcts and leukoencephalopathy (CADASIL) is a hereditary angiopathy caused by
      mutations in Notch3. Cerebral microvessels show an accumulation of granular
      osmophilic material in the vicinity of degenerating vascular smooth muscle cells.
      In this study, we measured the arteriovenous cerebral transit time (CTT) to
      identify changes related to the microangiopathy in CADASIL. METHODS: CTT is the
      time that a contrast agent needs to pass from a cerebral artery to its
      corresponding vein. CTT was measured in 17 CADASIL individuals (mean age, 50.2+/
      12.3 years) and an equal number of age- and sex-matched control subjects (mean
      age, 48.9+/-13.0 years) with transcranial color-coded duplex sonography. The
      intensity curves were recorded in the P2 segment of the posterior cerebral artery
      and the vein of Galen after injection of the ultrasound contrast agent Levovist.
      RESULTS: CTT was significantly prolonged in individuals with CADASIL (4.4+/-1.9
      seconds) compared with control subjects (1.3+/-0.5 seconds, P<0.0001). This
      difference was also significant when only nondisabled CADASIL individuals (Rankin
      score=0, n=9) were analyzed (P<0.0001). There was a nonsignificant trend for a
      correlation between Rankin score and CTT (r=0.39, P=0.11). CONCLUSIONS: The
      prolonged CTT likely reflects microvascular changes in CADASIL. Measurements of
      the CTT may be used clinically to disclose small-vessel disease. Studies
      comparing CADASIL subjects with other patient populations seem warranted to
      determine possible differences in CTT between different types of small-vessel
      disease.

PMID- 11823662
TI  - Association between influenza vaccination and reduced risk of brain infarction.
AB  - BACKGROUND AND PURPOSE: Because infections subsequent to influenza may play a
      role in promoting the complications of atherosclerotic disease and may also
      induce hypercoagulation, we hypothesized that influenza vaccination may protect
      against brain infarction. METHODS: During the influenza epidemic period we
      studied 270 subjects, including 90 consecutive patients older than 60 years
      admitted to the hospital for brain infarction and 180 population-based controls,
      matched for age, sex, and district of residency in Paris. We conducted a
      structured interview on whether they had been vaccinated during the last
      influenza vaccination campaign or every year during the 5 last years. RESULTS: We
      found significantly fewer vaccinated subjects during the last vaccination
      campaign among patients with brain infarction than among controls (46.7% versus
      59.4%; P=0.036) and fewer patients vaccinated every year during the last 5 years
      (41.1% versus 56.1%; P=0.017). After adjustment for age, traditional risk
      factors, and recent use of antibiotics, the risk of stroke was reduced in the
      subjects vaccinated during the year of the study and in those vaccinated during
      the last 5 years, with an odds ratio of 0.50 (95% CI, 0.26 to 0.94; P=0.033) and
      0.42 (95% CI, 0.21 to 0.81; P=0.009), respectively. Similar associations were
      observed in cases and controls free of previous cardiovascular history. Subjects
      younger than 75 years and subjects free of risk factors or in high social class
      were significantly less often vaccinated than controls. CONCLUSIONS: Influenza
      vaccination may protect against brain infarction by reducing infections or may
      identify a subgroup of patients at low risk for stroke because of a better
      lifestyle. These results give rise to a new hypothesis for research into stroke
      prevention.

PMID- 11823663
TI  - Effects of hypothermia on excitatory amino acids and metabolism in stroke
      patients: a microdialysis study.
AB  - BACKGROUND AND PURPOSE: The objective of this study was to assess the effect of
      therapeutic moderate hypothermia on excitatory amino acids and metabolism by
      applying cerebral microdialysis in patients suffering from space-occupying middle
      cerebral artery infarction. METHODS: This was an open, prospective, observational
      study of 12 patients undergoing moderate hypothermia (33 degrees C) as rescue
      therapy for large, life-threatening middle cerebral artery infarction.
      Microdialysis probes were placed concomitantly with intracranial pressure (ICP)
      measuring devices in the frontal lobe of the infarcted and/or noninfarcted
      hemisphere. Using the CMA 600 Microdialysis Autoanalyzer, we analyzed glutamate,
      glycerol, pyruvate, and lactate. RESULTS: According to follow-up cranial CT
      scans, 3 different compartments of microdialysis measurements could be defined.
      First, noninfarcted brain tissue had stable dialysate concentrations but a
      significant effect of hypothermia on glutamate (2.6 versus 3.6 micromol/L),
      lactate (1.8 versus 3 mmol/L), and pyruvate (50 versus 95.8 micromol/L). Second,
      measurements from peri-infarct tissue had a significant effect of hypothermia on
      glutamate (4.8 versus 12.6 micromol/L), glycerol (58 versus 82 micromol/L),
      lactate (0.7 versus 1.3 mmol/L), and pyruvate (13.3 versus 36.8 micromol/L).
      Third, dialysate concentrations obtained from irreversibly damaged tissue were
      excessive for glutamate (453 micromol/L), glycerol (1187 micromol/L), lactate (12
      micromol/L), and pyruvate (4 micromol/L). In this extreme compartment, no effect
      of hypothermia was observed. CONCLUSIONS: Cerebral microdialysis is a safe and
      feasible bedside method for neurochemical monitoring indicating normal brain
      tissue, potentially salvageable brain tissue, and irreversibly damaged areas in
      stroke. We could demonstrate that hypothermia decreases glutamate, glycerol,
      lactate, and pyruvate in the "tissue at risk" area of the infarct but not within
      the infarct core. Thus, future treatment strategies for life-threatening stroke
      should be guided by close neurochemical monitoring.

PMID- 11823664
TI  - Elevated cerebral blood flow velocities in Fabry disease with reversal after
      enzyme replacement.
AB  - BACKGROUND AND PURPOSE: Fabry disease is an X-linked inherited disorder resulting
      from a deficiency of alpha-galactosidase A. Cerebrovascular disease in Fabry
      disease includes small-vessel disease and larger-vessel ectasia in a
      predominantly posterior distribution. We assessed transcranial Doppler (TCD)
      blood flow velocities in naive and enzyme-treated Fabry patients. METHODS: TCD
      was used to noninvasively examine patients with Fabry disease for abnormal
      cerebral blood flow velocities. TCD measurements were also made during CO2
      retention by breathholding to examine cerebrovascular vessel reactivity. Twenty
      six patients were enrolled in a 6-month, double-blind, placebo-controlled trial
      of enzyme replacement therapy consisting of biweekly intravenous alpha
      galactosidase A infusions, with a subsequent 18-month follow-up in an open-label
      trial. Statistical analysis consisted of applying a mixed-effects ANOVA model for
      correlated outcomes. RESULTS: Peak velocity, mean velocity, pulsatility index,
      and resistance index were found to be significantly higher in patients compared
      with control subjects. When the individual vessels were considered, elevated flow
      velocities were found in the middle cerebral M1 branch and the posterior cerebral
      artery. Enzyme replacement therapy significantly decreased peak, mean, and end
      diastolic velocities and flow acceleration at the 18-month follow-up time point.
      CONCLUSIONS: Patients with Fabry disease have elevated cerebral blood flow
      velocities. These velocities significantly improved with enzyme replacement
      therapy.

PMID- 11823665
TI  - Progression of middle cerebral artery occlusive disease and its relationship with
      further vascular events after stroke.
AB  - BACKGROUND: Serial changes of flow velocities of transcranial Doppler ultrasound
      (TCD) in symptomatic middle cerebral artery (MCA) occlusive disease may be
      related to the occurrence of further vascular events, but prospective data are
      lacking. METHODS: We conducted a prospective study on patients with cerebral
      ischemia who were hospitalized with symptomatic MCA stenosis or occlusion. We
      repeated TCD examinations 6 months after the initial examinations and recorded
      any stroke or coronary events during this period. The changes of MCA flow
      velocities were categorized as normalized artery, stable artery, and progressed
      artery, which were determined according to the changes of MCA velocities at 6
      months. RESULTS: We studied 143 consecutive patients who had relevant MCA
      occlusive diseases (107 with stenosis and 36 with occlusion). At 6 months, the
      velocities in the MCA returned to normal in 42 patients (29%), they were stable
      in 80 patients (62%), and they progressed in 13 patients (9%). The number of
      clinical events varied significantly among the 3 groups: there were 2 patients
      (4.8%) with clinical events in the normal group, 11 patients (12.5%) with
      clinical events in the stable group, and 5 patients (38.5%) with clinical events
      in the progressed group (P=0.004). The 18 recurrent events included 10 recurrent
      strokes, 5 transient ischemic attacks, and 3 acute coronary syndromes.
      CONCLUSIONS: Progression of MCA occlusive diseases is associated with an
      increased risk of vascular events. Further studies are required to establish the
      value of serial TCD examinations in predicting future clinical events.

PMID- 11823666
TI  - Postoperative hyperthermia is associated with cognitive dysfunction after
      coronary artery bypass graft surgery.
AB  - BACKGROUND AND PURPOSE: Temperature is a well-known modulator of experimental
      cerebral injury. We hypothesized that hyperthermia would be associated with a
      worsened cognitive outcome after coronary artery bypass graft surgery (CABG).
      METHODS: Three hundred consenting patients undergoing cardiopulmonary bypass for
      CABG had hourly postoperative temperatures recorded. The degree of postoperative
      hyperthermia was determined by using the maximum temperature within the first 24
      hours as well as by calculating the area under the curve for temperatures >37
      degrees C. Patients underwent a battery of cognitive testing both before surgery
      and 6 weeks after surgery. By use of factor analysis, 4 cognitive domains
      (scores) were identified, and the mean of the 4 scores was used to calculate the
      cognitive index (CI). Cognitive change was calculated as the 6-week CI minus the
      baseline CI. Multivariable linear regression (controlling for age, baseline
      cognitive function, and temperature during cardiopulmonary bypass) was used to
      compare postoperative hyperthermia with the postoperative cognitive change.
      RESULTS: The maximum temperature within the first 24 hours after CABG ranged from
      37.2 degrees C to 39.3 degrees C. There was no relationship between area under
      the curve for temperatures >37 degrees C and cognitive dysfunction (P=0.45).
      However, the maximum postoperative temperature was associated with a greater
      amount of cognitive dysfunction at 6 weeks (P=0.05). CONCLUSIONS: This is the
      first report relating postoperative hyperthermia to cognitive dysfunction after
      cardiac surgery. Whether the hyperthermia caused the worsened outcome or whether
      processes that resulted in the worsened cognitive outcome also produced
      hyperthermia requires further investigation. In addition, interventions to avoid
      postoperative hyperthermia may be warranted to improve cerebral outcome after
      cardiac surgery.

PMID- 11823667
TI  - Higher incidence of falls in long-term stroke survivors than in population
      controls: depressive symptoms predict falls after stroke.
AB  - BACKGROUND AND PURPOSE: The incidence of falls among noninstitutionalized
      individuals with long-standing stroke has not been examined previously, although
      fractures are more common and the consequences more severe for stroke patients
      than for elderly people in general. METHODS: For 4 months (September to December
      1998), we followed 111 home-living patients who had suffered a stroke a mean of
      10 years previously and 143 control subjects randomly selected from the same
      municipality, matched with respect to age and sex. Falls were registered daily by
      use of "fall calendars." Before the fall registration period, information about
      morbidity, use of medication, and activities of daily living had been registered.
      Height, weight, vision, blood pressure, motor function, and body sway had been
      measured, and depressive symptoms as well as cognitive function had been
      assessed. RESULTS: During follow-up, 23% of the patients and 11% of the control
      subjects fell once or more, and the risk of falling at least once was more than
      twice as high for the patients with stroke, when controlled for potential
      confounders (relative risk=2.2; 95% CI, 1.1 to 4.3). Among the stroke patients,
      depressive symptomatology predicted falls, and the relative risk for falling
      increased by 1.5 per standard deviation increase in the depression score.
      CONCLUSIONS: We conclude that falls are more frequent among noninstitutionalized
      long-term stroke survivors than among community control subjects and that the
      risk of falling and depressive symptoms are related in stroke patients.

PMID- 11823668
TI  - Apolipoprotein e genotype and outcome in aneurysmal subarachnoid hemorrhage.
AB  - BACKGROUND AND PURPOSE: Active management of ruptured intracranial aneurysm in
      subarachnoid hemorrhage is indicated in patients with favorable prognosis.
      Outcome prediction is based on patient characteristics and clinical and
      radiological factors. Current clinical grading scales are imprecise, with low
      interobserver reproducibility. Therefore, outcome prediction remains inconsistent
      and decision making becomes difficult, especially for patients with poor clinical
      grade. METHODS: The possible relationship between apolipoprotein E genotype and
      the outcome of patients suffering spontaneous subarachnoid hemorrhage was
      investigated. A prospective study was conducted on all patients with spontaneous
      aneurysmal subarachnoid hemorrhage admitted to our unit during a 2-year period.
      All patients were managed according to standard protocol, and treatments were
      given according to their clinical grading. Patient characteristics, clinical
      grade, radiological grade, and apolipoprotein E genotype were documented. The
      focus of the study was the 6-month neurological outcome for this group of
      patients after they were discharged. RESULTS: Seventy-two patients with
      aneurysmal subarachnoid hemorrhage were admitted to the Prince of Wales Hospital
      in Shatin, Hong Kong, China, from February 1998 to February 2000. Their ages
      ranged from 24 to 95 years of age, with a mean (SD) age of 58.3 (15.0) years.
      Apolipoprotein E epsilon4 was found in 15 patients (21%). At 6 months, Glasgow
      Outcome Scale score < or = 3 was found in 29 patients (40%). Univariate analysis
      showed that older patients (odds ratio [OR], 1.03; 95% CI, 1.00 to 1.07; P=0.07)
      and patients with poor Fisher's grade (OR, 4.5; 95% CI, 1.3 to 15.2; P=0.01),
      poor World Federation of Neurological Surgeons grade (OR, 5.8; 95% CI, 1.9 to
      17.8; P=0.002), or apolipoprotein E epsilon4 (OR, 6.0; 95% CI, 1.7 to 21.3;
      P=0.006) were more likely to attain unfavorable outcome at 6 months. The
      additional effect of apolipoprotein E epsilon4 remained significant in the
      multiple logistic regression model (OR, 11.3; 95% CI, 2.2 to 57.0; P=0.003); the
      gain in predictive performance was not significant (P=0.26). CONCLUSIONS:
      Apolipoprotein E epsilon4 genotype is related to poor outcome in patients with
      subarachnoid hemorrhage.

PMID- 11823669
TI  - Speed-dependent treadmill training in ambulatory hemiparetic stroke patients: a
      randomized controlled trial.
AB  - BACKGROUND AND PURPOSE: A new gait training strategy for patients with stroke
      seeks to increase walking speed through treadmill training. This study compares
      the effects of structured speed-dependent treadmill training (STT) (with the use
      of an interval paradigm to increase the treadmill speed stepwise according to
      principles of sport physiology) with limited progressive treadmill training (LTT)
      and conventional gait training (CGT) on clinical outcome measures for patients
      with hemiparesis. METHODS: Sixty ambulatory poststroke patients were each
      randomly selected to receive 1 of the 3 different gait therapies: 20 subjects
      were treated with STT, 20 subjects were trained to walk on a treadmill with a 20%
      increase of belt speed over the treatment period (LTT), and 20 subjects were
      treated with CGT. Treatment outcomes were assessed on the basis of overground
      walking speed, cadence, stride length, and Functional Ambulation Category scores.
      RESULTS: After a 4-week training period, the STT group scored significantly
      higher than the LTT and CGT groups for overground walking speed (STT versus LTT,
      P<0.001; STT versus CGT, P<0.001), cadence (STT versus LTT, P=0.007; STT versus
      CGT, P<0.001), stride length (STT versus LTT, P<0.001; STT versus CGT, P<0.001),
      and Functional Ambulation Category scores (STT versus LTT, P=0.007; STT versus
      CGT, P<0.001). CONCLUSIONS: Structured STT in poststroke patients resulted in
      better walking abilities than LTT or CGT. This gait training strategy provides a
      dynamic and integrative approach for the treatment of gait dysfunction after
      stroke.

PMID- 11823670
TI  - Reduced risk of intracerebral hemorrhage with dynamic recreational exercise but
      not with heavy work activity.
AB  - BACKGROUND AND PURPOSE: It is unclear whether intracerebral hemorrhage (ICH) is
      associated with dynamic or static exercise. Our aim was to assess whether such an
      association exists. METHODS: A case-control study was undertaken involving 331
      consecutive cases of primary ICH and 331 age- and sex-matched community-based
      neighborhood controls. Cases, verified by CT or autopsy, were identified from 13
      major hospitals in Melbourne, Australia. A questionnaire was used to elicit
      information about lifetime physical activity at leisure and work and other
      potentially confounding factors. RESULTS: Individuals undertaking recent regular
      dynamic exercise exhibited an odds ratio (OR) for ICH of 0.63 (95% CI 0.39 to
      1.01) when adjustment was made for all potential confounding factors, except
      hypertension, cholesterol, and body mass index. Among men and women separately,
      the ORs were 0.51 (95% CI 0.27 to 0.97) and 1.22 (95% CI 0.52 to 2.87),
      respectively. When hypertension, cholesterol, and body mass index were also
      included in the multivariate model, the OR among men was 0.57 (95% CI 0.28 to
      1.14). There was no association between physical activity at work and ICH (OR
      1.14, 95% CI 0.58 to 2.25). CONCLUSIONS: These results provide preliminary
      evidence for a role of exercise in reducing the likelihood of ICH among men. In
      women, the CI was wide, and the association was not statistically significant.
      There was further support that factors other than blood pressure status,
      cholesterol, and body mass index may play a role in the observed inverse
      association between dynamic exercise and ICH among men.

PMID- 11823671
TI  - Physician advice, patient actions, and health-related quality of life in
      secondary prevention of stroke through diet and exercise.
AB  - BACKGROUND AND PURPOSE: Healthy diet and exercise are recommended for secondary
      prevention in stroke patients. We examined the prevalence of persons with stroke
      who received physician advice for, and engaged in, dietary change and exercise,
      and we also sought to determine whether engaging in these actions was associated
      with differences in health-related quality of life (HRQOL). METHODS: Data are
      from 51 193 participants in the 1999 Behavioral Risk Factor Surveillance System,
      a state-based telephone survey. The participants noted whether they were advised
      to eat fewer high fat/high cholesterol foods and to exercise more and whether
      they engaged in these activities. HRQOL measures were the reported number of the
      preceding 30 days when physical health was not good, mental health was not good,
      usual activities were limited, and both physical and mental health were good
      (healthy days). RESULTS: Overall, 2.4% of the participants reported a history of
      stroke. Sixty-one percent of those who reported a history of stroke had been
      advised to eat fewer high fat/high cholesterol foods, and 85.4% of those who had
      received such advice reported a dietary change compared with 56.0% of those who
      did not receive such advice. Almost 64% of those who reported a stroke had been
      advised to exercise more, and 76.5% of those who received such advice reported
      exercising more versus 38.5% of those who did not receive such advice. Persons
      with stroke who reported exercising had fewer limited activity days and days when
      physical health was not good and more healthy days than did persons who did not
      exercise. Dietary actions were not associated with differences in HRQOL.
      CONCLUSIONS: Results highlight the importance of provider advice for secondary
      prevention among persons with stroke.

PMID- 11823672
TI  - Effect of controlled release/extended release metoprolol on carotid intima-media
      thickness in patients with hypercholesterolemia: a 3-year randomized study.
AB  - BACKGROUND AND PURPOSE: Beta-adrenergic blockade has in several studies been
      shown to improve survival after myocardial infarction. In animal experiments beta
      blockers have also shown an antiatherosclerotic effect. The aim of this study was
      to test the hypothesis that the beta-blocker metoprolol succinate controlled
      release/extended release (CR/XL), when given to patients with
      hypercholesterolemia on concomitant lipid-lowering therapy, provides an
      additional antiatherosclerotic effect to that provided by the statins, measured
      as carotid intima-media thickness (IMT). METHODS: We conducted a randomized,
      double-blind, placebo-controlled, single center trial to compare the effect of
      metoprolol CR/XL (100 mg once daily) and placebo on the progression of carotid
      IMT during 36 months of treatment in patients with hypercholesterolemia and signs
      of early atherosclerosis in the carotid artery. Most patients were prescribed
      lipid-lowering treatment with statins. RESULTS: A highly significant difference
      in the progression rate of the composite variable of carotid bulb IMT+common
      carotid IMT was observed between the metoprolol CR/XL and placebo groups after 1
      year of treatment (-0.08 versus -0.01 mm; P=0.004), an effect that was sustained
      after 3 years of follow-up (-0.06 versus +0.03 mm; P=0.011). The patients had
      high levels of total cholesterol at randomization: 9.4 mmol/L in the metoprolol
      CR/XL group and 8.6 mmol/L in the placebo group. During the study the 2
      randomization groups were treated with lipid-lowering drugs, mainly statins, to a
      similar extent, and total cholesterol was reduced to 6.4 mmol/L at end of follow
      up in both groups. CONCLUSIONS: The results from the present study in patients
      with hypercholesterolemia under concomitant lipid-lowering therapy are the first
      clinical data to show an antiatherosclerotic effect of beta-blockade as
      additional therapy to statins. The data indicate that statin treatment and
      treatment with beta-blockers affect different mechanisms in the atherosclerotic
      process and have additive beneficial effects.

PMID- 11823673
TI  - Inhibition of factor IX(a) is protective in a rat model of thromboembolic stroke.
AB  - BACKGROUND AND PURPOSE: Although used clinically to prevent stroke, there are few
      examples of anticoagulant investigations in the treatment of acute thromboembolic
      stroke in animal models. The treatment of thromboembolic stroke in experimental
      models has been investigated almost exclusively around the use of tissue
      plasminogen activator (tPA). In this study, using a rat thromboembolic stroke
      model, we investigated the use of an inhibitory anti-factor IX(a) monoclonal
      antibody (SB 249417) for the treatment of thromboembolic stroke and compared its
      efficacy to that of tPA. METHODS: Stroke was initiated by delivering 6 clots into
      the internal carotid artery. After 2, 4, or 6 hours, rats received either
      intravenous vehicle, 10.0 mg/kg tPA, or 1.0, 2.0, or 3.0 mg/kg SB 249417. At 24
      hours after stroke, infarct volumes and neurological deficits were assessed.
      RESULTS: Treatment with tPA 2, 4, or 6 hours after stroke reduced infarct volumes
      by 35% (P=NS), 45%, and 39%, respectively. tPA treatment did not improve
      neurological deficits at any time point. Treatment with SB 249417 (3.0 mg/kg) 2,
      4, or 6 hours after stroke reduced infarct volumes by 44%, 50%, and 13% (P=NS),
      respectively. Neurological deficits were reduced by 49%, 42%, and 13% (P=NS),
      respectively. Neither mortality nor hemorrhage was affected by either treatment.
      CONCLUSIONS: The data indicate that the inhibition of factor IX(a) within 4 hours
      of thromboembolic stroke produced a more favorable outcome than tPA. When
      treatment was initiated 6 hours after stroke, the benefits of factor IX(a)
      inhibition were lost, whereas tPA continued to suppress lesion development,
      albeit without a corresponding improvement in functional deficits. This study
      suggests that cerebral ischemia and the resultant perfusion deficit are
      exacerbated by the activation of blood coagulation and that anticoagulants like
      SB 249417 may find utility in the treatment of ischemic stroke.

PMID- 11823674
TI  - Flow cytometric analysis of inflammatory cells in ischemic rat brain.
AB  - BACKGROUND AND PURPOSE: Inflammation plays a key role in cerebral ischemia
      through activation of microglia and infiltration by leukocytes. Flow cytometry is
      a well-established method for quantitative and qualitative analysis of
      inflammatory cells. However, this technique has not been applied to the study of
      cerebral ischemia inflammation. The aim of this study was to establish a flow
      cytometric method to measure inflammatory cells in ischemic brain. METHODS: To
      perform flow cytometry on brain tissue, we developed 2 cell-isolation methods
      based on different mechanical dissociation and Percoll gradient separation
      techniques. The methods were tested on a rat model of permanent middle cerebral
      artery occlusion. Morphological and immunophenotypic analyses, with the use of
      anti-CD11b, anti-CD45, and alphabeta T-cell receptor antibodies, were employed to
      identify and quantify inflammatory cells. RESULTS: Both methods gave consistent
      results in terms of yield and reproducibility. The cell suspension contained
      granulocytes, macrophages, lymphocytes, and neural cells. Morphological and
      immunophenotypic analyses enabled the identification of a cell-scatter gate (R1a)
      enriched in inflammatory cells. With both methods, a higher number of events in
      R1a were recorded in the ischemic hemisphere than in the nonischemic hemisphere
      (P< or =0.001). CD11b, CD45, and alphabeta T-cell receptor staining confirmed
      that this augmentation was a reflection of the increase in the number of
      granulocytes, cells of the monocytic lineage, and lymphocytes. CONCLUSIONS:
      Quantitative flow cytometric analysis of ischemic rat brain is feasible and
      provides a reliable and rapid assay to assess neuroinflammation in experimental
      models of brain ischemia.

PMID- 11823675
TI  - Phosphatidylinositol 3-kinase inhibitor failed to reduce cerebral vasospasm in
      dog model of experimental subarachnoid hemorrhage.
AB  - BACKGROUND AND PURPOSE: Phosphatidylinositol 3-kinase (PI3-kinase) is involved in
      smooth muscle contraction induced by growth factors and/or G protein-coupled
      receptor agonists. To evaluate the role of PI3-kinase in the pathogenesis of
      delayed vasospasm, we applied 2 PI3-kinase inhibitors to an established canine
      double-hemorrhage model of experimental subarachnoid hemorrhage. METHODS: Twenty
      four dogs underwent double blood injections via the cisterna magna on days 0 and
      2. The dogs were killed on day 7. Dogs were treated with either vehicle (dimethyl
      sulfoxide), wortmannin, or LY294002 once per day on day 2 through day 6.
      Angiography was performed before blood injection and before the dogs were killed.
      The basilar arteries were collected for morphology, Western blot analysis, and
      PI3-kinase activity. RESULTS: The residual diameter of the basilar arteries in
      the dimethyl sulfoxide treatment group, which was compared with day 0 angiogram,
      decreased markedly on day 7 (the percentage of the residual diameter was 47.8+/
      0.8%). Wortmannin and LY294002 did not significantly change residual diameter on
      day 7. Both PI3-kinase inhibitors abolished PI3-kinase activity compared with the
      vehicle treatment group. However, both PI3-kinase inhibitors failed to
      significantly attenuate PI3-kinase protein expression (Western blot) (P>0.05,
      ANOVA). CONCLUSIONS: Delayed treatment, which was to mimic the clinical
      situation, with PI3-kinase inhibitors failed to reverse vasospasm. PI3-kinase may
      not play an important role in the delayed vasospasm. The possible effect of PI3
      kinase inhibitors in the early stage of vasospasm was not investigated in the
      present study.

PMID- 11823676
TI  - 17beta-estradiol increases rat cerebrovascular prostacyclin synthesis by
      elevating cyclooxygenase-1 and prostacyclin synthase.
AB  - BACKGROUND AND PURPOSE: It has been reported that estrogens modulate peripheral
      vascular synthesis of vasodilatory hormones, including prostacyclin. If this
      occurs in the cerebral circulation, it could have important consequences in the
      modulation of cerebral hemodynamic function and improvement of stroke outcome. We
      investigated the hypothesis that in vivo 17beta-estradiol treatment of
      ovariectomized rats increases cerebrovascular prostacyclin production via
      elevation of the enzymes responsible for prostacyclin synthesis. METHODS:
      Cerebral blood vessels from 17beta-estradiol-treated and nontreated
      ovariectomized rats were isolated and examined for prostacyclin synthesis by
      enzyme-linked immunosorbent assay or for protein levels of cyclooxygenase-1,
      prostacyclin-synthase, and cytosolic phospholipase A2 by immunoblot analysis.
      RESULTS: We report that chronic in vivo 17beta-estradiol treatment significantly
      enhanced basal prostacyclin synthesis in rat cerebral blood vessels by 2.6-fold
      over control. 17beta-estradiol treatment also resulted in a 5.1-fold increase of
      cyclooxygenase-1 protein and a 6.7-fold increase of prostacyclin-synthase protein
      in the cerebral vasculature. There was no effect of estrogen on levels of
      cytosolic phospholipase A2. CONCLUSIONS: Our findings suggest that estrogen
      influences the biosynthesis of prostacyclin, which may be important in the
      regulation of cerebral blood flow and thrombosis. This finding may shed light on
      the mechanisms that govern sex-based differences in cerebrovascular disease.

PMID- 11823677
TI  - Penumbral microcirculatory changes associated with peri-infarct depolarizations
      in the rat.
AB  - BACKGROUND AND PURPOSE: This study was designed to investigate the influence of
      peri-infarct depolarization elicited by occlusion of the middle cerebral artery
      on the dynamics of the microcirculation. METHODS: The microcirculation in the
      frontoparietal cortex of 9 rats was visualized in real time through a closed
      cranial window with the use of laser-scanning confocal fluorescence microscopy
      combined with intravenous fluorescein isothiocyanate (FITC)-dextran and FITC
      labeled erythrocytes. The direct current potential/electrocorticogram was
      continuously monitored. Intraluminal focal ischemia was induced for 2 hours in 6
      rats anesthetized with halothane and mechanically ventilated. Reperfusion was
      monitored for 1 hour. Three rats underwent sham operation. Brains were removed 24
      hours after occlusion and processed for histology. RESULTS: In control
      conditions, the velocity of fluorescent erythrocytes through capillaries was
      0.51+/-0.19 mm/s (mean+/-SD), and the diameter of the arterioles studied was 33+/
      12 microm. Under ischemia, erythrocyte velocity through capillaries was
      significantly decreased to 0.33+/-0.14 mm/s, while arteriole diameter did not
      change significantly. During spontaneous peri-infarct depolarizations, arteriole
      diameter was significantly increased (119+/-23% of baseline), while capillary
      erythrocyte velocity was further decreased by 14+/-34%. The direction of
      arteriolar blood flow episodically and transiently reversed during approximately
      half of the peri-infarct depolarizations. The decrease in capillary erythrocyte
      velocity was more pronounced (23+/-37%) in these cases. After reperfusion, the
      microcirculatory variables rapidly returned to baseline. All rats in the ischemic
      group had infarcts 24 hours after occlusion. CONCLUSIONS: Peri-infarct
      depolarization has an adverse influence on penumbral microcirculation, reducing
      capillary perfusion by erythrocytes, despite dilatation of arterioles. These
      findings suggest that a steal phenomenon contributes to the deleterious effect of
      these depolarizations.

PMID- 11823678
TI  - Combined endothelial nitric oxide synthase upregulation and caveolin-1
      downregulation decrease leukocyte adhesion in pial venules of ovariectomized
      female rats.
AB  - BACKGROUND AND PURPOSE: We recently found that chronic estrogen depletion
      enhances leukocyte adhesion in pial venules in the female rat, while estrogen
      repletion decreases it. Estrogen-associated repression of inflammation may be due
      to upregulation of the endothelial isoform of nitric oxide synthase (eNOS) and
      concomitant downregulation of the endogenous inhibitor of eNOS, caveolin-1 (CAV
      1). In this study we examined the effects of estrogen-independent eNOS
      upregulation (via simvastatin) and/or CAV-1 downregulation (antisense) on pial
      venular leukocyte adhesion in ovariectomized (OVX) rats. METHODS: Intact and OVX
      rats were prepared with closed cranial windows. Adherent rhodamine 6G-labeled
      leukocytes were viewed by intravital microscopy. To demonstrate the importance of
      pial venular eNOS in the resistance to leukocyte adhesion, intact female rats
      were treated with a nonselective (N(G)-nitro-L-arginine) or a neuronal NOS
      selective (7-nitroindazole) inhibitor. In OVX females, leukocyte adhesion was
      compared in the following groups: (1) untreated; (2) treated with simvastatin;
      (3) treated with simvastatin plus CAV-1 antisense; (4) treated with simvastatin
      plus CAV-1 missense; (5) treated with CAV-1 antisense; and (6) treated with CAV-1
      missense. RESULTS: In intact females, pial venular leukocyte adhesion was
      increased when total NOS activity, but not neuronal NOS activity alone, was
      blocked. In OVX rats, basal leukocyte adhesion, measured as the percentage of
      venular area occupied by adherent leukocytes, was attenuated (by approximately
      equal 60%) only in the presence of combined simvastatin plus CAV-1 antisense
      treatment. CONCLUSIONS: Present findings demonstrate that eNOS-derived NO plays
      an important role in limiting cerebral venular leukocyte adhesion in female rats.
      These data also suggest that simvastatin-induced upregulation of eNOS expression
      in OVX rats will not restore eNOS function, as measured by decreased leukocyte
      adhesion, unless CAV-1 levels are reduced as well.

PMID- 11823679
TI  - What is effective in malignant middle cerebral artery infarction: reperfusion,
      craniectomy, or both? An experimental study in rats.
AB  - BACKGROUND AND PURPOSE: We sought to evaluate the effects of reperfusion and
      craniectomy treatment at different time points after middle cerebral artery (MCA)
      occlusion on infarct volume and neurological outcome in MCA infarction in rats.
      METHODS: We used an endovascular technique to obtain MCA occlusion in 182 rats.
      Thirteen groups with 14 animals each were investigated: control group 1 with no
      treatment; groups 2 to 7 with only reperfusion or craniectomy at 1, 4, or 12
      hours, respectively; and groups 8 to 13 with reperfusion at 1 or 4 hours combined
      with craniectomy at 1, 4, or 12 hours, respectively. We used infarct volume and
      neurological performance as study end points in all animals at day 7. RESULTS:
      Neurological score and infarct volume in animals undergoing early reperfusion at
      1 hour were significantly smaller (1.8/79+/-59 mm3) than those in control animals
      (3.8/225+/-26 mm3) (P<0.01). Reperfusion at 4 hours (2.8/182+/-62 mm3) and 12
      hours (3.7/231+/-69 mm3) did not result in significant improvement. Animals
      undergoing craniectomy at 1, 4, and 12 hours demonstrated significantly better
      outcome and significantly reduced infarct volume (1.6/96+/-30 mm3, 1.9/109+/-39
      mm3, and 2.6/150+/-34 mm3, respectively) (P<0.05). Compared with 1 treatment at a
      time, combined reperfusion and craniectomy did not result in a significant
      additional benefit. CONCLUSIONS: Early reperfusion and craniectomy at 1 hour are
      both effective in large MCA infarction. While reperfusion later than 1 hour was
      not beneficial, late craniectomy at 4 and 12 hours still resulted in significant
      improvement of neurological score and reduction of infarction size. Combined
      treatment at different time points yields no significant additional benefit
      compared with 1 treatment at a time.

PMID- 11823680
TI  - Stroke awareness and knowledge retention in children: The Brain Child Project.
AB  - BACKGROUND AND PURPOSE: Efforts at public education to improve adults' response
      to stroke symptoms continue to be disappointing, and very little has been
      developed to improve the knowledge base of children regarding brain attacks.
      Children may be able to exert a positive influence on adult behavior and to learn
      positive healthcare habits, which will also influence their own health. METHODS:
      A total of 561 children enrolled in grades kindergarten through eighth (K-8),
      participated in The Brain Child Project, which included (1) assessment of their
      knowledge of stroke awareness (including initiation of the emergency medical
      system [EMS]) using a multiple-choice questionnaire, (2) attendance at a
      multimedia educational program designed to increase stroke knowledge, followed by
      (3) immediate administration of the same questionnaire, and (4) a final
      administration of the same questionnaire 10 days later to measure retention of
      acquired learning. RESULTS: The results showed that these children had a limited
      understanding of stroke, but with a brief educational program, all grades
      significantly increased their scores on the average from 64% to 82%. The loss of
      knowledge between the posttest and the retention test was negligible.
      CONCLUSIONS: The results of this study indicate that through brief education,
      children show significant improvement in their knowledge of and response to brain
      attacks. Future efforts in this direction may positively affect stroke
      prevention, response and outcomes. A national program could be implemented in the
      school systems much like heart disease programs, with the ultimate goal of
      greater public awareness and prevention of stroke.

PMID- 11823681
TI  - High rate of recanalization of middle cerebral artery occlusion during 2-MHz
      transcranial color-coded Doppler continuous monitoring without thrombolytic drug.
AB  - BACKGROUND AND PURPOSE: Experimental evidence indicates that ultrasound can
      accelerate thrombolysis. We report our findings on early recanalization during
      transcranial color-coded Doppler (TCCD) continuous monitoring in acute stroke
      patients with middle cerebral artery (MCA) main stem occlusion. METHODS: We
      performed continuous TCCD monitorings in 6 consecutive patients with acute MCA
      main stem occlusion using a 2-MHz transducer. Patients were not treated with
      recombinant tissue plasminogen activator. RESULTS: Partial recanalization,
      defined as blunted waveforms, occurred during monitoring in 5 patients (83%). The
      mean time to beginning of recanalization was 17.2+/-9.6 minutes. Complete
      recanalization at 24 hours occurred in only 1 patient. The mean National
      Institutes of Health Stroke Scale score in the patients who recanalized during
      monitoring was 21.2+/-4.1 at baseline, 19.2+/-5 at 2 hours, and 15.6+/-3.4 at 24
      hours (P=0.1). CONCLUSIONS: In this short series of patients with acute MCA main
      stem occlusion, not treated with recombinant tissue plasminogen activator, we
      found a high rate of early partial recanalization during continuous exposure to 2
      MHz ultrasound.

PMID- 11823683
TI  - Systematic review of nimodipine.

PMID- 11823682
TI  - Costs and benefits of carotid endarterectomy and associated preoperative arterial
      imaging: a systematic review of health economic literature.
AB  - BACKGROUND AND PURPOSE: Carotid endarterectomy (CEA) reduces the risk of stroke
      in patients with severe stenosis of the internal carotid artery. However, the
      cost implications of this procedure have not yet been satisfactorily addressed.
      The objective of this systematic review was to critically appraise the studies
      addressing the economic implications of CEA and the associated preoperative
      arterial imaging. METHODS: A systematic search strategy was developed to identify
      research articles related to the economic evaluation of CEA and the associated
      preoperative imaging. MEDLINE, EMBASE, and BIOSIS were electronically searched,
      and reference lists from identified studies were searched manually. Methods used
      to critically appraise these studies followed proposed guidelines for an economic
      evaluation that addresses 10 distinct aspects under 3 separate headings. RESULTS:
      Studies identified were either partial economic or full economic evaluations,
      with the majority coming from the United States. The methodological quality seems
      to have improved over time. The studies that assessed cost-effectiveness of CEA
      were all modeling studies; although the same baseline parameters were used,
      divergent conclusions were reached. Variation in the cost estimates of CEA ($9500
      to $11 500) in the same health care system was also observed in the studies
      reporting only on the cost of carotid surgery. For a symptomatic patient, the
      benefit of CEA ranged from 0.35 quality adjusted life years (QALYs) (4.2 months)
      at a cost of $4100 per QALY to 0.93 QALYs (11.2 months) at a cost of $434 per
      QALY. For an asymptomatic patient, the cost-effectiveness of CEA varied from 0.15
      QALYs (1.8 months) at a cost of $52 700 per QALY to 0.25 QALYs (3 months) at a
      cost of $8004 per QALY. CONCLUSIONS: Divergent conclusions of the cost
      effectiveness of CEA were reported from studies that addressed the same questions
      and using similar parameters in their models. The cost estimates of the procedure
      and the different time periods used in the studies might explain these
      inconsistencies. Modeling studies in hypothetical cohorts might also be to blame.
      The cost-effectiveness of CEA will only definitively be assessed when real
      patient data are used.

PMID- 11823684
TI  - Effect of age on cerebral blood flow velocity in patients after aneurysmal
      subarachnoid hemorrhage.

PMID- 11823685
TI  - Conjugate eye deviation with head version due to a cortical infarction of the
      frontal eye field.

PMID- 11823686
TI  - Long-term outcome in stroke patients and caregivers following accelerated
      hospital discharge and home-based rehabilitation.

PMID- 11823687
TI  - Postoperative radiotherapy for carcinoma of the prostate: impact on both local
      control and distant disease-free survival.
AB  - The role of postoperative irradiation in patients with clinically localized
      prostate cancer, either as an adjuvant or salvage radiotherapy, remains
      controversial. In this study, we evaluate the impact of postoperative
      radiotherapy on patients diagnosed with prostate cancer with respect to
      biochemical and clinical disease free survival. Between 1987 and 1996, 179
      patients with clinically localized prostate cancer were found to have adverse
      histopathologic findings on radical prostatectomy specimens (positive surgical
      margins, extracapsular extension, and seminal vesicle invasion). Of these
      patients, 42 were referred for postoperative adjuvant radiotherapy, whereas 73
      were referred for salvage irradiation because of rising serum prostate-specific
      antigen (PSA) levels postoperatively. The remaining 64 patients underwent
      prostatectomy only. The 10-year biochemical relapse-free survival (RFS) from date
      of surgery were 88%, 45%, and 25% for patients treated with postoperative
      adjuvant radiotherapy, salvage irradiation, and with surgery alone, respectively
      (p = 0.046). Ten-year distant RFS from date of surgery were 82%, 74%, and 44% for
      adjuvantly treated patients, those with salvage radiotherapy, and those with
      surgery alone, respectively (p = 0.0180). Ten-year overall disease RFS from date
      of surgery was 89%, 76%, and 30% for adjuvantly treated patients, those with
      salvage radiotherapy, and those with surgery alone, respectively (p = 0.0237).
      Multivariate analyses revealed that a preoperative PSA greater than 20 ng/ml and
      pathologic Gleason Score of 8 to 10 were adverse predictors for biochemical
      relapse, whereas pathologic Gleason Score of 8 to 10, seminal vesicle invasion,
      and extracapsular extension were adverse predictors of distant metastases.
      Postoperative radiotherapy, either delivered as adjuvant treatment for adverse
      histopathologic findings or as salvage therapy for local relapses, appear to
      confer superior local, distant disease RFS, and overall disease RFS than surgery
      alone.

PMID- 11823688
TI  - Brachytherapy for locally recurrent soft-tissue sarcoma.
AB  - Radiation is used to reduce potential risk of local recurrence from microscopic
      residual disease after surgical resection. Brachytherapy is a clinically
      established means of providing radiation for soft-tissue sarcomas that recur
      after surgical resection alone or surgical resection and radiation. Although the
      total dose of radiation that is prescribed is approximately the same for patients
      undergoing external beam radiation or brachytherapy, the radiobiologic
      characteristics of brachytherapy, based on the inverse-square law, provide higher
      doses of radiation to the surgical bed. This provides a theoretical advantage for
      the use of brachytherapy as compared with external beam radiation among patients
      with recurrence after surgical resection. When soft-tissue sarcomas recur in a
      previously irradiated area, further external beam radiation generally is not
      possible; therefore, brachytherapy allows a radiotherapeutic alternative in an
      attempt to reduce the risk of further local recurrence. Recommendations for
      patient selection, the total dose of radiation, and the radiation dose-rate are
      outlined. Standard grading systems for response, symptoms, and severity of
      complications should be used.

PMID- 11823689
TI  - Malignant fibrous histiocytoma: a retrospective study of 109 cases.
AB  - The purpose of this report is to assess the prognostic factors that could
      influence management and clinical outcome of malignant fibrous histiocytoma (MFH)
      of soft tissues. Between 1975 and 1998, 109 patients diagnosed with MFH of the
      soft tissues, seen at King Faisal Specialist Hospital and Research Center, have
      been reviewed. Of the 109 patients, 75 were men and 34 were women. The median age
      at presentation was 48 years (range: 3-94). Seven patients (6%) had regional
      nodal disease and 10 other patients (9%) with distant metastases were excluded
      from survival analysis. The remaining 92 patients had localized disease and had
      surgery as the primary treatment modality with or without radiotherapy and/or
      chemotherapy. Extremities were the most common location (58%). Tumors less than 5
      cm represented 32%, whereas 68% had tumors 5 cm or more. Low-grade tumors
      constituted 46%, and the remaining 54% were high grade. Thirty-seven percent of
      patients had positive surgical margins histologically after complete gross
      resection. The 5- and 10-year relapse-free survival (RFS) rates were 39% and 36%,
      respectively. Isolated local recurrence occurred in 20 patients (22%), isolated
      metastatic disease without local recurrence in 9 patients (10%), and combined
      local and metastatic disease occurred in 20 patients (22%). The overall 5- and 10
      year overall survival (OS) rates were 50% and 43%, respectively. On multivariate
      analysis, tumor size and radiation dose were significant factors for RFS (p =
      0.04 and 0.0005, respectively). In terms of OS, size, histologic grade, and
      surgical margins were significant factors on multivariate analysis (p = 0.001.
      0.006, and 0.0001, respectively). Complete surgical resection at the time of
      primary tumor presentation is likely to afford the best chance for RFS and OS.
      Radiation therapy plays an important role, in combination with surgery for better
      local control, particularly in high-grade lesions, and in cases with positive
      surgical margins after wide complete gross excision. The role of adjuvant
      chemotherapy remains investigational.

PMID- 11823690
TI  - A phase III study of 5-fluorouracil versus 5-fluorouracil plus interferon alpha
      2b versus 5-fluorouracil plus leucovorin in patients with advanced colorectal
      cancer: a Hellenic Cooperative Oncology Group (HeCOG) study.
AB  - We conducted a phase III study in patients with advanced colorectal carcinoma
      (ACC). The total number of patients randomized from October 1993 until July 1998
      was 192, whereas therapy was started on 179 and 158 (82.3%) have been evaluable.
      The treatment schedules consisted of weekly bolus administration for 6 weeks of 5
      fluorouracil (5-FU), 600 mg/m2 (arm I) versus 5-FU (500 mg/m2) intravenous bolus
      and interferon-alpha, 5 MU subcutaneously, three times a week (arm II) versus
      leucovorin 200 mg/m2 in 2-hour infusion and 5-FU 500 mg/m2 intravenous bolus at
      the midtime of leucovorin infusion (arm III) followed by a 2-week rest period.
      Treatment was continued for six cycles or until progression. This study failed to
      show any superiority of the modulated 5-FU versus single administration of 5-FU.
      There were no significant differences between the three arms in the overall
      response rate (10.3% versus 11.3% versus 12.9%, p = 0.95), the time to tumor
      progression (median, 3.9 versus 3.8 versus 6.0 months, p = 0.59), or survival
      duration (median, 14.7 versus 12.4 versus 16.3 months, p = 0.71). The incidence
      of severe (grades III and IV) toxicity was significantly higher in patients in
      arm II and III (24.5% and 18.6%) versus arm I (6.0%) (p = 0.01). Because
      modulated 5-FU failed to show superiority versus 5-FU, new agents and new
      strategies are needed for the treatment of advanced colorectal carcinoma.

PMID- 11823691
TI  - Severe pulmonary toxicity in a patient treated with gemcitabine.
AB  - Gemcitabine is a pyrimidine analog of deoxycytidine with activity against
      nonhematologic and hematologic malignancies. Its pulmonary toxicity is usually
      mild and self-limiting. We describe a male patient with lung cancer in whom
      severe dyspnea and interstitial infiltrates developed after the administration of
      gemcitabine.

PMID- 11823692
TI  - External beam radiation therapy in the treatment of patients with extranodal
      stage IA non-Hodgkin's lymphoma.
AB  - The purpose of this report was to study the results of external beam radiotherapy
      for patients with extranodal stage IA non-Hodgkin's lymphoma (NHL). A
      retrospective review was carried out on 27 patients seen between 1984 and 1998
      with stage IA NHL of extranodal sites, and followed up for a minimum of 1 year.
      Sites involved included eye/orbit (seven), parotid (five), breast (four),
      Waldeyer ring (four), thyroid (three), other head and neck (two), stomach (one),
      and prostate (one). All patients had biopsy-proven disease and underwent staging
      workup to rule out other sites of disease. Histologic analysis revealed 16
      patients with low-grade NHL, 9 with intermediate-grade, and 2 with high-grade.
      Ten patients received chemotherapy before radiation therapy, and eight of them
      had a complete response. The remaining 17 patients were treated with external
      beam radiation therapy alone. Radiation was directed to the involved field at 1.8
      Gy to 2.0 Gy per fraction to a median dose of 40 Gy (range: 20-50.4 Gy). The
      median patient age was 71 years (range: 39-85 years); 55% were female, and 45%
      were male. A complete response was attained in all 27 patients after radiation
      therapy. There were five failures (all in uninvolved distant sites), and two
      deaths during the follow-up. Median disease free survival (DFS) and overall
      survival (OS) have not been reached. The 5-year DFS and OS are 85% and 94%,
      respectively. Older age at presentation showed a trend toward worse outcome (p =
      0.07), but because of the relatively few events, other factors (radiation dose,
      grade of disease, sex, or the use of chemotherapy) showed no statistical
      differences among the patients. External beam radiation therapy is a highly
      effective treatment for stage IA NHL found in extranodal sites.

PMID- 11823693
TI  - Prognostic role of angiogenesis in operable carcinoma of the gallbladder.
AB  - The prognostic significance of intratumoral angiogenesis was investigated in 62
      patients with stage I-III carcinomas of the gallbladder treated with simple
      cholecystectomy. Microvessel density (MVD) was assessed immunohistochemically,
      using the alkaline phosphatase/anti-alkaline phosphatase method and the
      monoclonal antibody CD31. The mean MVD was 30.5 vessels per x 200 optical field.
      Using the thirty-third and the sixty-sixth percentile, the patients were grouped
      into three MVD categories: low (MVD 9-18; 20 patients), medium (MVD 19-31; 20
      patients), and high (MVD 32-86; 22 patients). A high MVD was more frequent in
      well-differentiated adenocarcinomas compared with moderately and poorly
      differentiated tumors (p = 0.04), but there was no statistically significant
      association between MVD and T stage, or patients' age or sex. Multivariate
      analysis, including MVD, T stage, and histologic grade, showed that MVD was a
      significant independent prognostic factor in carcinomas of the gallbladder (p =
      0.001, t ratio 3.3). It is believed that the assessment of intratumoral
      angiogenesis in patients with operable gallbladder carcinomas may be useful in
      predicting prognosis and, perhaps, in decision making for postoperative adjuvant
      treatment.

PMID- 11823694
TI  - Radiation treatment of recurrent pheochromocytoma of the bladder: case report and
      review of literature.
AB  - Secondary to the paucity of pheochromocytoma, very limited data exist regarding
      the optimal treatments of metastatic disease. Malignant pheochromocytomas are
      often considered unresponsive to radiotherapy, but this decision is based on the
      few case reports performed before 1970. There have been a handful of reports
      about metastatic resolution and palliation from radiation therapy. Nevertheless,
      radiotherapy is not considered a mainstay of pheochromocytoma treatment. In this
      case report, we describe a patient with a malignant extraadrenal
      pheochromocytoma, metastatic to the right humerus, and her treatment course of
      surgery and radiotherapy.

PMID- 11823695
TI  - Phase II trial of pyrazoloacridine in recurrent platinum-resistant ovarian
      cancer: a Gynecologic Oncology Group study.
AB  - The Gynecologic Oncology Group performed a Phase II study to determine the
      response rate of pyrazoloacridine (PZA) in patients with platinum-resistant
      ovarian cancer. PZA was administered at a dose of 750 mg/m2 intravenously over 3
      hours every 3 weeks. Among 24 evaluable patients, there was 1 (4.2%) complete and
      1 (4.2%) partial response. The major toxicities were hematologic. With the dose
      and schedule used, PZA had only modest activity in this population.

PMID- 11823696
TI  - Radiotherapy after lumpectomy for breast cancer in very old women.
AB  - During a 15-year period, 47 women aged 80 to 89 years, with 48 breast cancers,
      were treated with postlumpectomy radiotherapy after lumpectomy alone (31 breast
      cancers) or lumpectomy and axillary dissection (17 breast cancers). Forty-three
      breast cancers in 42 women were invasive carcinomas, and 5 women had ductal
      carcinoma in situ. Forty-six breasts were treated with whole breast irradiation
      with a usual dose of 5,000 cGy in 25 fractions. Six women were treated with
      accelerated regimens of 250 cGy/d to 300 cGy/d to 4,000 cGy to 4,500 cGy. An
      additional boost to the operative area was administered to 34 breasts. Two women
      were treated with radiotherapy just to the operative area of the involved breast
      with 3,600 cGy and 3,700 cGy in 10 fractions, respectively. Thirty-four women
      received adjuvant tamoxifen. Twenty-five women (53.2%) are alive and free of
      disease at 21 to 156 months from surgery (median: 43 months). Seventeen women
      died at 14 to 159 months after surgery (median: 65.5 months). Twelve of these
      women survived greater than 5 years from treatment. Distant metastases have
      developed in only two women. One died at 68 months after treatment and one is
      alive with disease at 34 months. There are no patients with known local-regional
      recurrence. Radiotherapy was well tolerated in all patients, and the majority had
      a good to excellent cosmetic result. Age alone is not a contraindication to the
      administration of postlumpectomy breast irradiation.

PMID- 11823698
TI  - Phase IV study of liposomal daunorubicin (DaunoXome) in AIDS-related Kaposi
      sarcoma.
AB  - The purpose of this article was to study the efficacy and tolerance of liposomal
      daunorubicin (DaunoXome) in the treatment of AIDS-associated Kaposi sarcoma (KS)
      as prescribed in France between September 1996 and September 1997. All patients
      with a positive HIV serology, histologically proven KS, and having received at
      least one daunorubicin treatment cycle during the study period were eligible for
      entry. Ninety-four patient files from 13 university hospital departments were
      retrospectively studied. Of 94 patients, 80% received cytostatic treatment before
      the first daunorubicin treatment cycle. Initial mean CD4 lymphocyte count was
      114/microl. Ninety percent of the patients received highly active antiretroviral
      treatment (HAART) during daunorubicin treatment. Daunorubicin was administered as
      single chemotherapy to 70% of the patients. The total number of treatment cycles
      was 1,422, with a mean number of 16.1 treatment cycles (1-68) per patient and a
      mean cumulative daunorubicin dose of 674 mg/m2 (40-2,749). According to the AIDS
      Clinical Trial Group criteria, partial and complete response rates were 26.5% and
      11.5%, respectively. A hematopoietic growth factor was prescribed in 29% of the
      treatment cycles. At the final evaluation, 71% of the patients were alive. No
      severe cardiotoxic event was observed despite high cumulative drug doses and
      prolonged follow-up. Since the introduction of HAART, this study constitutes the
      only evaluation of daunorubicin in a wide population. Our study confirms that
      daunorubicin is effective in patients with advanced KS. Daunorubicin is well
      tolerated over the long term in association with HAART.

PMID- 11823697
TI  - Role of postoperative radiotherapy in the management of Merkel cell carcinoma.
AB  - Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine tumor of the
      skin with a high potential of locoregional relapse after surgery alone. This
      report is an update of our experience in the treatment of MCC. From January 1990
      to May 2000, 31 patients with MCC, 13 men and 18 women aged between 34 and 92
      years, were treated at the University of Cologne, Germany. Primary tumor sites
      were in the head and neck region in 13 patients, limbs in 13, and trunk in 5. The
      tumors were stage I in 26 of 31 patients, stage II in 4 of 31 and stage III in 1
      of 31. Treatment included surgery alone in 14 of 31 patients, adjuvant
      postoperative radiotherapy in 16 of 31 patients, 1 of them had incomplete
      surgery, and definitive radiotherapy in 1 of 31 patients (stage III). Median
      overall survival (OS) after first diagnosis was 32 months (95% confidence
      interval: 0-75 months) with a 3-year OS rate of 47% (95% CI: 25-69%). Six of 31
      patients relapsed locally after a median of 4 months, 10 of 31 patients developed
      regional node metastases, and 7 of 31 patients distant metastases. Nine patients
      died as a direct result of MCC. Locoregional control and disease-free survival
      were significantly improved in the group with postoperative radiotherapy (p =
      0.023). Uni- and multivariate analysis revealed that head and neck location of
      the tumor and the lack of postoperative radiotherapy are unfavorable prognostic
      factors. Postoperative radiotherapy to the primary tumor region and the regional
      lymphatics is effective in the prevention of locoregional recurrence. Prospective
      clinical trials should be performed to confirm these observations.

PMID- 11823699
TI  - Intratumoral doxorubicin in patients with malignant brain gliomas.
AB  - The objective of the study was to evaluate the safety and therapeutic efficacy of
      intralesional administration of doxorubicin in brain gliomas. Ten patients with
      recurrent grade III or IV glioma were enrolled in the study, after the second
      operation. All patients had not responded to radiation therapy. Chemotherapy was
      administered directly in the tumor through an Ommaya pump placed in the site of
      disease at the time of craniotomy. Doxorubicin 0.5 mg was administered in the
      Ommaya reservoir every 24 hours on days 1 to 10. Patients were evaluated at 6- to
      8-week intervals until tumor progression and death. All patients were evaluated
      for response. Six of 10 patients had clinical improvement lasting from 12 to 73
      weeks. Objective radiologic response was observed in 5 of 10 (50%) patients. One
      patient achieved complete response with time to disease progression of 119 weeks,
      and 4 patients had a partial response (duration 14-39 weeks) with 25% or more
      reduction of tumor volume on computed tomography scan compared with pretreatment
      measurements. Time to disease progression in patients who responded after the
      intratumoral chemotherapy was 39.83 +/- 40.5 weeks. One additional patient had
      stable disease for a duration of 12 weeks. The median survival of the patients
      with response was 55.17 +/- 54.22 weeks (range: 21-164 weeks), whereas survival
      of those who did not respond was 17.0 +/- 12.36 weeks (range: 8-35) (Mann Whitney
      U test: z = -2.13, p = 0.033). The median survival of all 10 patients was 39.9 +/
      45.52 weeks (range: 8-73 weeks). Bifrontal headache was reported in 4 of 10
      patients immediately after the administration of doxorubicin. There were no other
      clinically significant adverse reactions either in the brain or systematically.
      Intralesional administration of doxorubicin appears to be a safe and effective
      treatment and should be further explored in the management of brain gliomas
      resistant to conventional forms of treatment.

PMID- 11823700
TI  - Irinotecan (CPT-11) in combination with infusional 5-fluorouracil and leucovorin
      (de Gramont regimen) as first-line treatment in patients with advanced colorectal
      cancer: a multicenter phase II study.
AB  - The combination of CPT-11 with 5-fluorouracil (5-FU) in advanced colorectal
      cancer (ACC) represents an attractive approach. A phase II study was conducted to
      assess the tolerance and efficacy of CPT-11 in combination with leucovorin
      modulated bolus plus infusional 5-FU given according to the de Gramont regimen in
      chemonaive patients with ACC. Fifty-four patients with histologically confirmed
      ACC were enrolled. The patients' median age was 65 years; 30 (55.5%) patients
      were men; performance status (World Health Organization) was 0 in 27 (50%)
      patients, 1 in 22 (41%), and 2 in 5 (9%). Patients received leucovorin (200
      mg/m2/d) as a 2-hour intravenous infusion, followed by 5-FU as an intravenous
      bolus at 400 mg/m2/d, and then as a 22-hour continuous infusion at 600 mg/m2/d,
      repeated on 2 consecutive days. CPT-11 (180 mg/m2; 30-minute intravenous
      infusion) was administered on day 1, simultaneously with leucovorin
      administration. This cycle was repeated every 2 weeks. Complete response was
      achieved in 4 patients (8%) and partial response in 19 (37%) (overall response
      rate: 45%; 95% CI: 24-50.5%). Stable disease was achieved in 16 (31%) patients
      and progressive disease in 13 (25%). The median duration of response and the
      median TTP were 5 and 8 months, respectively. After a median follow-up period of
      11 months, 33 (61%) patients are still alive; the median overall survival has not
      yet been reached. Thrombocytopenia and anemia were very rare. Grade III/IV
      neutropenia developed in 19 patients (36%); febrile neutropenia developed in 4
      patients, and 1 of them died of sepsis. Grade IV diarrhea was seen in 7 (13%)
      patients, and 4 of them required hospitalization. Grade III and IV mucositis was
      observed in two (4%) and one (2%) patients, respectively. Other toxicities were
      mild. The combination of CPT-11 and bolus plus infusional 5-FU is a relatively
      well-tolerated and effective first-line treatment in ACC. Final results from
      large phase III trials are awaited to clarify whether the CPT-11/5-FU
      combinations should be considered as "standard" first-line treatment in ACC.

PMID- 11823701
TI  - A phase II study of etoposide, doxorubicin, and carboplatin in the treatment of
      advanced gastric cancer.
AB  - Many phase II studies have reported improved response rates with severe toxicity
      of etoposide, doxorubicin (Adriamycin), and cisplatin in advanced gastric cancer.
      In an attempt to obtain a better regimen with high efficacy and less toxicity, a
      combination regimen of etoposide, doxorubicin, and carboplatin (EAC) had been
      developed and evaluated in this phase II study. Forty-six patients with advanced
      gastric cancer were enrolled in the study. The treatment consisted of doxorubicin
      20 mg/m2 given intravenously on days 1 and 7, etoposide 70 mg/m2 intravenously on
      days 4, 5, and 6, and carboplatin 200 mg/m2 intravenously on days 2 and 8.
      Therapy was repeated every 4 weeks. Patients who had stable disease or who
      responded, received an additional two to six cycles of therapy. Among 45 patients
      evaluable for response and toxicity, there was a 49% objective response rate,
      including 7% complete remission and 42% partial response. There was 11% stable
      disease and 27% progressive disease. Among 11 patients with lymph node metastasis
      only after a curative gastrectomy, there was an 82% objective response rates with
      27% having complete remission and 55% having partial response. The median follow
      up was 16 months. The median survival duration of all 45 patients was 11 months.
      The median time to progression was 5 months. The main toxicity was
      myelosuppression, with a high incidence of 82% leukopenia but only 9% of grades
      III to IV. Gastrointestinal toxicity was mild, with a low incidence of 42% nausea
      and vomiting and only 2% of grades III to IV. There were no chemotherapy-related
      deaths. With mild and tolerable toxicity, the EAC regimen in our study has active
      antitumor activity in advanced gastric cancer, which may have a positive
      influence on long-term survival time. It has a high efficacy, especially in
      patients with lymph node metastasis only after a curative gastrectomy. This
      regimen deserves further clinical studies for testing activity and toxicity in
      advanced gastric cancer.

PMID- 11823702
TI  - Prognostic factors for local control in non-small-cell lung cancer treated with
      definitive radiation therapy.
AB  - Radiotherapy plays an important role as a treatment for locally advanced non
      small-cell lung cancer (NSCLC), but local failure still occurs in 70% to 80% of
      the patients. A retrospective analysis was carried out to evaluate the local
      control predictors for non-SCLC. From January 1990 to December 1996, 256 patients
      with stages I-IIIb NSCLC entered this analysis. All patients received definitive
      radiotherapy. The significance of prognostic variables on local control was
      evaluated using univariate analysis and Cox stepwise regression model. The
      prognostic index was calculated according to the value of each prognostic factor
      on local control. Median local progression-free survival time of the whole group
      was 9.7 months, and 1-, 3-, and 5-year actuarial local progression-free survival
      were 54%, 24%, and 19%, respectively. Univariate and multivariate analyses showed
      patients with smaller tumor volume, earlier clinical staging, and treated with
      higher total dose in shortened overall treatment time had better local control.
      Tumor volume, clinical staging, and radiotherapy methods were independent
      prognostic factors on local control. The prognostic index model could predict the
      local control condition of NSCLC treated with radiation therapy more effectively
      than a single variable such as TNM staging.

PMID- 11823703
TI  - Late adrenal metastasis in operable non-small-cell lung carcinoma.
AB  - Treatment of early-stage (I, II, and some IIIA) non-small-cell lung cancer
      (NSCLC) is curative resection. Simultaneous isolated adrenal metastasis
      represents a dilemma. Although many studies addressing the management of adrenal
      metastasis diagnosed simultaneously with NSCLC have been published, only very few
      reports of late adrenal metastasis can be found in the literature. Our purpose is
      to discuss the management of solitary late (metachronous) adrenal metastasis from
      operable NSCLC based on published experience. We describe a patient with a
      solitary metachronous adrenal metastasis diagnosed 3 years after resection of
      NSCLC. Adrenalectomy was done, followed by combination chemotherapy with
      paclitaxel and carboplatin. MEDLINE literature on similar cases was reviewed and
      updated. Only 18 cases have been reported from 1965 to 2000. The median interval
      between the diagnosis of NSCLC and development of adrenal metastasis was 11.5
      months. All patients were male. Unilateral adrenal metastases were reported in 15
      patients, whereas 3 had bilateral metastases. Five patients were treated with
      adrenalectomy, and eight patients were treated with adrenalectomy and
      postoperative adjunctive chemotherapy. Chemotherapy alone was used in two
      patients and two patients underwent palliative radiation therapy. One patient was
      treated with intraarterial chemotherapy followed by radiation therapy. Solitary
      metachronous adrenal metastases are rare. There are no standard treatment
      guidelines for this group of patients. Review of the literature showed that
      median survival after treatment was 19 months for the group treated with
      adrenalectomy followed by chemotherapy; 15 months for the chemotherapy group; 14
      months for the adrenalectomy group; and 8 months for the group treated with
      palliative radiation.

PMID- 11823704
TI  - Adenocarcinoma of the stomach: univariate and multivariate analysis of factors
      associated with survival.
AB  - Gastric cancer is the most frequent tumor of the digestive tract in Mexico. Most
      patients are diagnosed at advanced stages, and fatal outcome is expected. One
      hundred fifty patient charts were retrospectively reviewed. Univariate and
      multivariate analyses were performed to evaluate the impact of clinicopathologic
      and treatment variables on survival. Most patients (75%) were at advanced stages,
      harboring poorly differentiated tumors. Surgery, mostly palliative, was performed
      on 114 patients. Chemotherapy was administered to 47 patients. On univariate
      analysis, significant prognostic factors were TNM stage, chemotherapy, surgical
      attempt, performance status, histology, and tumor site (p < 0.001). On
      multivariate analysis, independent prognostic factors were TNM stage, histology,
      tumor site, surgical attempt, and chemotherapy (p < 0.01). Median survival for
      patients with palliative or adjuvant chemotherapy was 11.4 and 10.4 months,
      respectively, compared with +/- 3 months for patients with no chemotherapy (p <
      0.03). Nonsurgical patients receiving chemotherapy survived 5.4 months versus 1.1
      months for those without chemotherapy. The favorable influence of chemotherapy
      persisted after a stratified analysis of subgroups eliminating potential biases.
      We identified prognostic factors for survival. Chemotherapy should be considered
      even for advanced-stage patients with either adjuvant or palliative attempts,
      because we consistently found a favorable impact on the median survival time.
      However, phase III prospective randomized trials are awaited.

PMID- 11823705
TI  - Concomitant weekly cisplatin and thoracic radiotherapy for Pancoast tumors of the
      lung: pilot experience of the San Antonio Cancer Institute.
AB  - Pancoast (superior sulcus tumors) comprise a subset of non-small-cell lung
      cancers that have a unique clinical presentation by virtue of the locoregional
      pattern of disease progression. We herein report a brief report on our group's
      pilot experience in managing these challenging lung neoplasms with an aggressive
      concomitant modality approach. These results and those of the recent Southwest
      Oncology-lead Intergroup prospective phase 2 trial (SWOG-9416/INT-0160) support
      the use of concomitant chemoradiation followed by an attempt at surgical
      resection.

PMID- 11823706
TI  - Nasopharyngeal carcinoma treated with external radiotherapy, brachytherapy, and
      concurrent/adjuvant chemotherapy.
AB  - The standard treatment for advanced nasopharyngeal carcinoma (NPC) has become
      external beam radiation therapy (EBXRT) 70 Gy/7 weeks + 3 cycles of concurrent
      cisplatin followed by 2 to 3 cycles of adjuvant cisplatin/5-fluorouracil (5-FU).
      Some reports suggest that the addition of low-dose rate brachytherapy to EBXRT
      also improves local control. To our knowledge, this is the first report of the
      "triple" combination of EBXRT, brachytherapy, and concurrent/adjuvant
      chemotherapy. Eleven patients treated from 1992 to 1998 were evaluated. All
      patients had stage III/IV (excluding T4 lesions) NPC. Treatment consisted of
      EBXRT (64-70 Gy/7 weeks), followed by a brachytherapy boost (6-15 Gy delivered
      0.5 cm deep to the mucosa). Chemotherapy consisted of concurrent cisplatin (100
      mg/m2) and post-XRT adjuvant cisplatin (80 mg/m2) and 5-FU (1,000 mg/m2/day x 4
      days) for 2 cycles. All 11 patients were evaluable. The average age was 44 years,
      and median follow-up was 38 months (range: 23-82 months). Median EBXRT dose was
      66 Gy, and median brachytherapy dose was 9 Gy (median total dose: 75 Gy). All
      patients obtained primary tumor complete response (CR). Two patients required
      post-XRT neck dissection to achieve regional CR. To date, 10 patients are alive
      with no evidence of disease. The 3-year actuarial survival is 100%. One patient
      died at 82 months of a late distant recurrence (at 37 months post-XRT). No
      patient has had a local or neck failure. Chemoradiation plus brachytherapy offers
      encouraging survival and local-regional control. Further study of this regimen as
      an alternative or adjunct to intensity-modulated EBXRT is warranted.

PMID- 11823707
TI  - Gemcitabine-induced pulmonary toxicity: case report and review of the literature.
AB  - Gemcitabine is a pyrimidine analog with a similar chemical structure and
      mechanism of action, as cytarabine. It has been shown to be a highly active agent
      for non-small cell lung cancer, pancreatic cancer, urothelial cancer, breast
      cancer and ovarian cancer. Gemcitabine is relatively well tolerated and
      myelosuppression is the dose-limiting toxicity. Pulmonary toxicity with
      gemcitabine is relatively uncommon, but a well recognized entity, associated with
      significant morbidity and mortality. A high index of suspicion, early diagnosis
      and timely intervention with oxygen supplementation, steroids, and diuretics is
      necessary to manage patients with this complication.

PMID- 11823708
TI  - Multifractionated dosing for chemotherapy with flexible cytokine use: strategy
      for optimizing the therapeutic index.

PMID- 11823709
TI  - External beam radiotherapy and intraluminal brachytherapy in advanced inoperable
      esophageal cancer: JIPMER experience.

PMID- 11823710
TI  - Pineal germ cell tumor metastasis via ventriculoperitoneal shunt.

PMID- 11823711
TI  - Molecular pathways of protein synthesis inhibition during brain reperfusion:
      implications for neuronal survival or death.
AB  - Protein synthesis inhibition occurs in neurons immediately on reperfusion after
      ischemia and involves at least alterations in eukaryotic initiation factors 2
      (eIF2) and 4 (eIF4). Phosphorylation of the alpha subunit of eIF2 [eIF2(alphaP)]
      by the endoplasmic reticulum transmembrane eIF2alpha kinase PERK occurs
      immediately on reperfusion and inhibits translation initiation. PERK activation,
      along with depletion of endoplasmic reticulum Ca2+ and inhibition of the
      endoplasmic reticulum Ca2+ -ATPase, SERCA2b, indicate that an endoplasmic
      reticulum unfolded protein response occurs as a consequence of brain ischemia and
      reperfusion. In mammals, the upstream unfolded protein response components PERK,
      IRE1, and ATF6 activate prosurvivial mechanisms (e.g., transcription of GRP78,
      PDI, SERCA2b ) and proapoptotic mechanisms (i.e., activation of Jun N-terminal
      kinases, caspase-12, and CHOP transcription). Sustained eIF2(alphaP) is
      proapoptotic by inducing the synthesis of ATF4, the CHOP transcription factor,
      through "bypass scanning" of 5' upstream open-reading frames in ATF4 messenger
      RNA; these upstream open-reading frames normally inhibit access to the ATF4
      coding sequence. Brain ischemia and reperfusion also induce mu-calpain-mediated
      or caspase-3-mediated proteolysis of eIF4G, which shifts message selection to m 7
      G-cap-independent translation initiation of messenger RNAs containing internal
      ribosome entry sites. This internal ribosome entry site-mediated translation
      initiation (i.e., for apoptosis-activating factor-1 and death-associated protein
      5) can also promote apoptosis. Thus, alterations in eIF2 and eIF4 have major
      implications for which messenger RNAs are translated by residual protein
      synthesis in neurons during brain reperfusion, in turn constraining protein
      expression of changes in gene transcription induced by ischemia and reperfusion.
      Therefore, our current understanding shifts the focus from protein synthesis
      inhibition to the molecular pathways that underlie this inhibition, and the role
      that these pathways play in prosurvival and proapoptotic processes that may be
      differentially expressed in vulnerable and resistant regions of the reperfused
      brain.

PMID- 11823712
TI  - TNF-alpha-induced tolerance to ischemic injury involves differential control of
      NF-kappaB transactivation: the role of NF-kappaB association with p300 adaptor.
AB  - Preconditioning with sublethal ischemia results in natural tolerance to ischemic
      stress, where multiple mediators of ischemic damage are simultaneously
      counteracted. Tumor necrosis factor alpha (TNF-alpha) has been implicated in
      development of ischemic tolerance. Using cellular models of ischemic tolerance,
      we have demonstrated that an effector of TNF-alpha-induced preconditioning is
      ceramide, a sphingolipid messenger in TNF-alpha signaling. TNF-alpha/ceramide
      induced preconditioning protected cultured neurons against ischemic death and
      cultured astrocytes against proinflammatory effects of TNF-alpha. TNF-alpha
      activates a transcription factor NF-kappaB that binds promoters of multiple
      genes, thus ensuring pleiotropic effects of TNF-alpha. We describe here a
      mechanism that allows selective suppression of TNF-alpha/NF-kappaB-induced
      harmful genes in preconditioned cells while preserving cytoprotective responses.
      We demonstrate that in astrocytes activation of an adhesion molecule ICAM-1 by
      TNF-alpha is regulated through association of the phosphorylated p65 subunit of
      NF-kappaB with an adapter protein, p300, and that in preconditioned cells p65
      remains unphosphorylated and ICAM-1 transcription is inhibited. However, TNF
      alpha-activated transcription of a protective enzyme, MnSOD, does not depend on
      p300 and does not become inhibited in preconditioned cells. This new
      understanding of TNF-alpha-induced adaptation to ischemic stress and inflammation
      could suggest novel avenues for clinical intervention during ischemic and
      inflammatory diseases.

PMID- 11823713
TI  - Gene expression profiling in perilesional and contralateral areas after ischemia
      in rat brain.
AB  - Structural and functional reorganization in the vicinity of damaged neocortex and
      other connected brain areas seems to be responsible for postlesional functional
      recovery. To better understand the molecular mechanisms underlying this type of
      plasticity, gene expression patterns were analyzed by using DNA macroarrays
      comprising 1176 genes. Circumscribed unilateral infarcts consistently affecting
      the forelimb area of the motor cortex were induced photochemically in adult rats.
      Ten days after lesioning, cortical gene expression fingerprints were evaluated
      from an area adjacent to the lesion as well as two contralateral areas of motor
      and somatosensory cortex. Discrete regions showed distinct expression patterns.
      Upregulation was observed of different members of transcription factors,
      immediate early genes, neuronal signaling as well as neuronal growth and
      structure-associated genes, ipsilaterally (six genes) and/or contralaterally
      (eight genes in the motor and seven in the somatosensory cortex). In contrast,
      downregulations were restricted to ipsilateral areas and included genes coding
      for ion channels, transport proteins, mediators of metabolic pathways, and
      intracellular transducers (14 genes). A subset of these regulations were further
      confirmed by real-time polymerase chain reaction (TaqMan assay). At least part of
      the detected regulations, in particular those of the contralateral hemisphere,
      are likely to underlie plasticity processes.

PMID- 11823714
TI  - Rapid tolerance to focal cerebral ischemia in rats is attenuated by adenosine A1
      receptor antagonist.
AB  - Two types of ischemic tolerance in the brain, rapid and delayed, have been
      reported in terms of the interval between the conditioning and test insults.
      Although many reports showed that delayed-phase neuroprotection evoked by
      preconditioning is evident after 1 week or longer, there have been a few
      investigations about rapidly induced tolerance, and the reported neuroprotective
      effects become ambiguous 7 days after the insults. The authors examined whether
      this rapid ischemic tolerance exists after 7 days of reperfusion in a rat focal
      ischemic model, and investigated modulating effects of the adenosine A 1 receptor
      antagonist DPCPX (8-cyclopentyl-1,3-dipropylxanthine). Preconditioning with 30
      minutes of middle cerebral artery occlusion reduced infarct volume 7 days after
      180 minutes of subsequent focal ischemia given after 1-hour reperfusion. The
      rapid preconditioning also improved neurologic outcome. These beneficial effects
      were attenuated by pretreatment of 0.1 mg/kg DPCPX, which did not influence the
      infarct volume after conditioning (30 minutes) or test (180 minutes) ischemia
      when given alone. The results show that preconditioning with a brief focal
      ischemia induces rapid tolerance to a subsequent severe ischemic insult, the
      effect of which is still present after 7 days of reperfusion, and that the rapid
      ischemic tolerance is possibly mediated through an adenosine A 1 receptor-related
      mechanism.

PMID- 11823716
TI  - 17-beta-estradiol induces heat shock proteins in brain arteries and potentiates
      ischemic heat shock protein induction in glia and neurons.
AB  - Estradiol reduces brain injury from many diseases, including stroke and trauma.
      To investigate the molecular mechanisms of this protection, the effects of 17
      beta-estradiol on heat shock protein (HSP) expression were studied in normal male
      and female rats and in male gerbils after global ischemia. 17-beta-estradiol was
      given intraperitoneally (46 or 460 ng/kg, or 4.6 microg/kg) and Western blots
      performed for HSPs. 17-beta-estradiol increased hemeoxygenase-1, HSP25/27, and
      HSP70 in the brain of male and female rats. Six hours after the administration of
      17-beta-estradiol, hemeoxygenase-1 increased 3.9-fold (460 ng/kg) and 5.4-fold
      (4.6 microg/kg), HSP25/27 increased 2.1-fold (4.6 microg/kg), and Hsp70 increased
      2.3-fold (460 ng/kg). Immunocytochemistry showed that hemeoxygenase-1,
      HSP25/27,and HSP70 induction was localized to cerebral arteries in male rats,
      possibly in vascular smooth muscle cells. 17-beta-estradiol was injected
      intraperitoneally 20 minutes before transient occlusion of both carotids in adult
      gerbils. Six hours after global cerebral ischemia, 17-beta-estradiol (460 ng/kg)
      increased levels of hemeoxygenase-1 protein 2.4-fold compared with ischemia
      alone, and HSP25/27 levels increased 1.8-fold compared with ischemia alone.
      Hemeoxygenase-1 was induced in striatal oligodendrocytes and hippocampal neurons,
      and HSP25/27 levels increased in striatal astrocytes and hippocampal neurons.
      Finally, Western blot analysis confirmed that estrogen induced heat shock factor
      1, providing a possible mechanism by which estrogen induces HSPs in brain and
      other tissues. The induction of HSPs may be an important mechanism for estrogen
      protection against cerebral ischemia and other types of injury.

PMID- 11823715
TI  - Inhibition of cyclin-dependent kinases improves CA1 neuronal survival and
      behavioral performance after global ischemia in the rat.
AB  - Increasing evidence suggests that cyclin-dependent kinases participate in
      neuronal death induced by multiple stresses in vitro. However, their role in cell
      death paradigms in vivo is not well characterized. Accordingly, the authors
      examined whether cyclin-dependent kinase inhibition resulted in functionally
      relevant and sustained neuroprotection in a model of global ischemia.
      Intracerebroventricular administration of the cyclin-dependent kinase inhibitor
      flavopiridol, immediately or at 4 hours postreperfusion after a global insult,
      reduced injury in the CA1 of the hippocampus when examined 7 days after
      reperfusion. No significant protection was observed when flavopiridol was
      administered 8 hours after reperfusion. The tumor-suppressor retinoblastoma
      protein, a substrate of cyclin-dependent kinase, was phosphorylated on a cyclin
      dependent kinase consensus site after the global insult; this phosphorylation was
      inhibited by flavopiridol administration. Importantly, flavopiridol had no effect
      on core body temperature, suggesting that the mechanism of neuroprotection was
      through cyclin-dependent kinase inhibition but not through hypothermia.
      Furthermore, inhibition of cyclin-dependent kinases improved spatial learning
      behavior as assessed by the Morris water maze 7 to 9 days after reperfusion.
      However, the histologic protection observed at day 7 was absent 28 days after
      reperfusion. These results indicate that cyclin-dependent kinase inhibition
      provides an extended period of morphologic and functional neuroprotection that
      may allow time for other neuroprotective modalities to be introduced.

PMID- 11823717
TI  - Local cerebral blood flow during lithium-pilocarpine seizures in the developing
      and adult rat: role of coupling between blood flow and metabolism in the genesis
      of neuronal damage.
AB  - Coupling between local cerebral blood flow and local cerebral metabolic rate for
      glucose is involved in the pathogenesis of epilepsy-related neuronal damage in
      the adult brain; however, its role in the immature brain is unknown. Lithium
      pilocarpine-induced status epilepticus is associated with extended damage in
      adult rats, mostly in the forebrain limbic areas and thalamus, whereas damage was
      moderate in 21-day-old rats (P21) or absent in P10 rats. The quantitative
      autoradiographic [14C]iodoantipyrine technique was applied to measure the
      consequences of lithium-pilocarpine status epilepticus on local cerebral blood
      flow. In adult and P21 rats, local cerebral blood flow rates increased by 50% to
      400%; the highest increases were recorded in regions showing damage in adults. At
      P10, local cerebral blood flow rates decreased by 40% to 60% in most areas,
      except in some forebrain regions showing no change during status epilepticus. In
      areas injured when status epilepticus was induced in adults, a strong
      hypermetabolism (Fernandes et al., 1999) not matched by comparable local cerebral
      blood flow increases was present in rats of all ages, whereas in damage-resistant
      areas, local cerebral metabolic rate for glucose and local cerebral blood flow
      remained coupled in the three age groups. Thus, the level of coupling between
      blood flow supply and metabolism is not involved in seizure-related brain damage
      in the developing brain, which appears to be resistant to the consequences of
      such a mismatch.

PMID- 11823718
TI  - Role of intracellular calcium stores in cell death from oxygen-glucose
      deprivation in a neuronal cell line.
AB  - To determine the role of calcium homeostasis in ischemic neuronal death, the
      authors used an in vitro model of oxygen-glucose deprivation in neuronal cell
      lines. Exposure of human neuroblastoma SH-SY5Y cells to 10-to 16-hour oxygen
      glucose deprivation decreased viability to 50% or less, and longer exposure times
      killed almost all cells. The death following 10-to 16-hour oxygen-glucose
      deprivation was not manifested until 24 to 72 hours after exposure. Deprivation
      of both glucose and oxygen together was required for expression of toxicity at
      these exposure times. Dantrolene, which blocks the release of endoplasmic
      reticulum Ca2+ stores, partially protected SH-SY5Y cells from oxygen-glucose
      deprivation toxicity. The addition of dantrolene during the deprivation phase
      alone produced the maximal drug effect; no further protection was obtained by
      continued drug exposure during the recovery phase. Prevention of Ca2+ influx by
      chelation or channel blockade or the chelation of cytosolic Ca2+ did not inhibit
      oxygen-glucose deprivation toxicity. In contrast, increasing extracellular Ca2+
      or stimulating Ca2+ influx did inhibit toxicity. Calcium measurements with fura-2
      acetoxymethylester revealed that oxygen-glucose deprivation caused a significant
      reduction in thapsigargin-releasable endoplasmic reticular stores of Ca2+. These
      studies suggest that an important component of the neuronal toxicity in cerebral
      ischemia is due to disruption of calcium homeostasis, particularly to the
      depletion of intracellular Ca2+ stores.

PMID- 11823719
TI  - Glycoprotein IIb/IIIa antagonist, murine 7E3 F(ab') 2, and tissue plasminogen
      activator in focal ischemia: evaluation of efficacy and risk of hemorrhage with
      combination therapy.
AB  - Tissue hypoperfusion during cerebral ischemia results from occlusion of large and
      small vessels. Combination treatment strategies using fibrinolytics to
      thrombolyse an embolic clot and antiplatelet agents to prevent reocclusion and
      the formation of new platelet thrombi in the microcirculation may offer
      advantages over single-agent therapy. The authors report on the effects of tissue
      plasminogen activator (rt-PA), a glycoprotein (GP) IIb/IIIa receptor antagonist,
      7E3 F(ab') 2, or a combination of the two agents in a focal embolic model of
      cerebral ischemia in Wistar rats. Focal ischemia was produced by introducing an
      autologous thrombus into the right side middle cerebral artery. Forty-six male
      Wistar rats were randomly divided into 6 groups: control (n = 8), 7E3 F(ab') 2 (n
      = 9, 6 mg/kg), rt-PA (n = 9, 10 mg/kg), rt-PA (n = 6, 20 mg/kg), and 7E3 F(ab') 2
      with either 10 mg/kg (n = 10) (low-dose combination) or 20 mg/kg (n = 6) (high
      dose combination) rt-PA. Evaluation of neurobehavioral scores, cerebral
      angiography, bleeding time, and measurement of brain infarction volume were used
      to determine efficacy. All actively treated groups showed a significant reduction
      in the infarct volume. Animals treated with 7E3 F(ab') 2 showed reduced
      infarction volumes (24.0 +/- 5.1%) compared with controls (42.43 +/- 5.6%, P <
      0.02). Treatment with rt-PA significantly reduced infarction volume (20.7 +/-
      3.3, = 0.01) at 10 mg/kg and at 20 mg/kg (19.5 +/- 8.2%, P < 0.05). Compared with
      vehicle-treated animals, the low-dose combination (16.4 +/- 5.5, P < 0.003) and
      high-dose combination (23.7 +/- 6.2%, P < 0.05) showed significant reduction in
      infarction volume. Cerebral angiography revealed significantly better
      recanalization in the combination group (5/6 animals in the high dose and 4/6 in
      low dose) compared with animals treated with 7E3 F(ab') 2 (3/10) or rt-PA alone
      (2/6). Bleeding time significantly increased from 11.25 +/- 1.9 minutes in the
      control group to 17 +/- 3.1 minutes in the rt-PA group, 24.5 +/- 2.6 minutes in
      the 7E3 F(ab') 2 group, 25.7 +/- 3.1 minutes in the low-dose combination group,
      and 32.5 +/- 4.7 minutes in the high-dose combination group. The incidence of
      intercerebral hemorrhage was highest in the high-dose combination group (6 of 6
      animals) and lowest in the single treatment with 7E3 F(ab') 2 alone (1 of 10
      animals) ( P < 0.05). Our data show that murine 7E3 F(ab') 2 alone has
      therapeutic effects when used after cerebral ischemia. Although this study
      suggests that higher doses of thrombolytic combined with anti-GPIIb/IIIa therapy
      may increases the risk of intracranial hemorrhage, the data also support the
      notion that anti-GPIIb/IIIa agents can safely be combined with low doses of
      thrombolytic agent to produce significant attenuation of neuronal damage with no
      increase in the incidence of cerebral hemorrhage.

PMID- 11823720
TI  - Imaging brain amyloid of Alzheimer disease in vivo in transgenic mice with an
      Abeta peptide radiopharmaceutical.
AB  - Abeta 1-40 is a potential peptide radiopharmaceutical that could be used to image
      the brain Abeta amyloid of Alzheimer disease in vivo, should this peptide be made
      transportable through the blood-brain barrier in vivo. The blood-brain barrier
      transport of [ 125 I]-Abeta 1-40 in a transgenic mouse model was enabled by
      conjugation to the rat 8D3 monoclonal antibody to the mouse transferrin receptor.
      The Abeta 1-40 -8D3 conjugate is a bifunctional molecule that binds the blood
      brain barrier TfR and undergoes transport into brain and binds the Abeta amyloid
      plaques of Alzheimer disease. App SW /Psen1 double-transgenic and littermate
      control mice were administered either unconjugated Abeta 1-40 or the Abeta 1-40 
      8D3 conjugate intravenously, and brain scans were obtained 6 hours later.
      Immunocytochemical analysis showed abundant Abeta immunoreactive plaques in the
      brains of the App SW /Psen1 transgenic mice and there was a selective retention
      of radioactivity in the brains of these mice at 6 hours after intravenous
      administration of the conjugate. In contrast, there was no selective
      sequestration either of the conjugate in control littermate mouse brain or of
      unconjugated Abeta 1-40 in transgenic mouse brain. In conclusion, the results
      show that it is possible to image the Abeta amyloid burden in the brain in vivo
      with an amyloid imaging agent, provided the molecule is conjugated to a blood
      brain barrier drug-targeting system.

PMID- 11823721
TI  - Increase in dopamine turnover occurs early in Parkinson's disease: evidence from
      a new modeling approach to PET 18 F-fluorodopa data.
AB  - An increase in dopamine turnover has been hypothesized to occur early in
      Parkinson's disease (PD) as a compensatory mechanism for dopaminergic neuronal
      loss. A new approach to the determination of dopamine turnover was developed
      using 4-hour-long 18 F-fluorodopa (FD) positron emission tomography (PET) data.
      An effective dopamine turnover, an estimate of dopamine turnover, has been
      measured using its inverse, the effective dopamine distribution volume (EDV).
      This new method is based on a reversible tracer approach and determines the EDV
      using a graphical method. Six healthy subjects and 10 subjects with very early PD
      underwent a 4-hour-long FD scan. The EDV and the plasma uptake rate constant
      K(i), a marker of dopamine synthesis and storage, were compared according to
      their ability to separate the PD group from the healthy group. The EDV was the
      better discriminator (93.8% correct classification versus 81.3% for K(i)).
      Effective dopamine distribution volume decreased by 65% in the PD group relative
      to the healthy group, whereas the decrease in K(i) was 39%. These results show
      that changes in EDV are measurable with PET earlier than changes in the dopamine
      synthesis and storage rate, indicating that EDV is a sensitive marker for early
      PD and that a dopamine turnover increase likely serves as an early compensatory
      mechanism.

PMID- 11823724
TI  - Type 2 diabetes management.

PMID- 11823722
TI  - Modified regression model for the Logan plot.
AB  - Logan's graphical model is a robust estimation of the total distribution volume
      (DVt) of reversibly bound radiopharmaceuticals, but the resulting DVt values
      decrease with increasing noise. The authors hypothesized that the noise
      dependence can be reduced by a linear regression model that minimizes the sum of
      squared perpendicular rather than vertical (y) distances between the data points
      and fitted straight line. To test the new method, 15 levels of simulated noise
      (repeated 2,000 times) were added to synthetic tissue activity curves, calculated
      from two different sets of kinetic parameters. Contrary to the traditional
      method, there was no ( P > 0.05) or dramatically decreased noise dependence with
      the perpendicular model. Real dynamic 11C (+) McN5652 serotonin transporter
      binding data were processed either by applying Logan analysis to average counts
      of large areas or by averaging the Logan slopes of individual-voxel data. There
      were no significant differences between the parameters when the perpendicular
      regression method was used with both approaches. The presented experiments show
      that the DVt calculated from the Logan plot is much less noise dependent if the
      linear regression model accounts for errors in both the x and y variables,
      allowing fast creation of unbiased parametric images from dynamic positron
      emission tomography studies.

PMID- 11823725
TI  - The role of the primary care team in support of informal carers.
AB  - Caring for an elderly, frail or disabled person has effects on physical and
      psychological health as well as financial and social consequences. There are 6
      million informal carers in the UK and the primary care team together with other
      community services is expected to provide the support they need. However, most
      primary care team members feel ill equipped to do so and there is very little
      evidence about which interventions are effective. This article reviews the
      reasons for this problem and suggests a strategy primary care team members could
      adopt until new evidence about effective strategies is available.

PMID- 11823726
TI  - Use of pressure reducing seats and cushions in a community setting.
AB  - It is generally accepted that sitting for long periods of time without frequent
      repositioning or provision of appropriate cushions or chairs can lead to pressure
      ulcer development in people who are elderly, frail, immobile or neurologically
      impaired. When sitting, in comparison to lying, only a small surface area of the
      body is providing support, predominantly the buttocks and thighs, and the feet.
      Therefore, interface pressures are much greater in sitting than lying. Sitting
      for long periods of time can result in the person adopting poor posture, which in
      turn can lead to the development of pressure ulcers, particularly on the
      buttocks, sacrum, greater trochanter and heels. Assessment and provision of
      appropriate seating equipment for people at risk is often difficult for
      clinicians working in the community. This article aims to describe the problems
      experienced by people who sit for long periods of time, to discuss where people
      should go in order to obtain help with seating needs, and outline some of the
      potential solutions to poor seating which are available to community staff.

PMID- 11823727
TI  - Meeting demand for clinical placements in one community trust.
AB  - The effective management of learning in clinical practice is assuming growing
      significance for all health-care organizations. This is due to various
      professional and political imperatives that underscore the need to produce
      increasing numbers of practitioners who are sufficiently skilled to be deemed
      'fit for practice', and must also be prepared to use their skills in different
      ways in a 'modernized' NHS. This article explores some of the ways in which one
      community trust has responded to this challenge, a challenge compounded by the
      need for extended final year medical student primary and community care
      placements. It also attempts to illustrate the extent to which we have recognized
      the importance of adopting an interprofessional approach to learning in and about
      practice.

PMID- 11823728
TI  - Teaching in partnership: linking a medical school and a community trust.
AB  - Since 1997, the Croydon and Surrey Downs Community NHS Trust, together with the
      Department of General Practice and Primary Care at Guy's, King's and St Thomas'
      School of Medicine, King's College London, has offered a community-based special
      study module to second year medical students. The module offered an opportunity
      to learn how people living with a chronic infection, such as HIV/AIDS, cope with
      their condition while being looked after by a multidisciplinary team in the
      community. This article describes how interprofessional teaching and supervision
      between community nurse specialists and medical students, with the involvement of
      multidisciplinary and community-based teachers, enabled active engagement of
      students in their learning. We also discuss the learning outcomes for the
      students and the benefits for the community trust staff in the context of
      interprofessional teaching.

PMID- 11823729
TI  - Evidence informing practice: introducing the mini-review.

PMID- 11823730
TI  - Self-monitoring of glucose levels for people with type 2 diabetes.
AB  - To determine the most effective way of monitoring glucose levels as an indicator
      of glycaemic control in people with type 2 diabetes in the community, we
      conducted a criteria-based review of randomized controlled trials and systematic
      reviews of randomized controlled trials that studied the efficacy of various
      glucose monitoring strategies. We searched the Cochrane Library, Medline, Embase,
      CINAHL and BNIPlus databases for relevant studies. The journals 'Diabetes',
      'Diabetic Medicine', 'Diabetologica', 'Evidence-Based Medicine' and 'Evidence
      Based Nursing' were hand searched. The outcome of interest was glycaemic control,
      as measured by glycated haemoglobin (HbA(1c)). A total of 642 titles were
      identified from the search; three studies answered the question criteria and only
      one study met all the quality criteria. The study that met the criteria was a
      systematic review of four trials measuring the efficacy of self-monitoring of
      glucose levels. The reduction in HbA(1c) in those who monitored glucose levels
      was estimated to be -0.25% (95% Cl -0.61 - +0.10). This result shows a small
      improvement, but it is not statistically significant. A meta-analysis was also
      performed on three studies (n=278) comparing HbA(1c) in subjects who performed
      blood glucose monitoring with those who performed urine monitoring. The reduction
      in HbA(1c) when monitoring blood glucose rather than urine glucose was -0.03%
      (95% Cl -0.52 - +0.47). This result is not statistically significant. The
      efficacy of blood and urine glucose monitoring testing, for people with type 2
      diabetes, in improving glycaemic control as measured by HbA(1c) levels is still
      questionable. A rigorous randomized controlled trial is needed to establish these
      answers although there is no evidence of harm. Clinical protocols that make
      recommendations for glucose monitoring strategies for people with type 2 diabetes
      should acknowledge that the evidence is weak. There is no basis to recommend one
      method above another.

PMID- 11823731
TI  - Focusing on local health needs and promoting new partnerships.
AB  - Government reports have stressed the importance of community-based interventions
      in addressing health inequalities. This article discusses the pivotal role played
      by a health visitor and school nurse team in identifying the health needs of a
      local community and working in partnership with local people, key community
      groups, health and youth workers to address these specific needs. A health needs
      assessment highlighted the need for a parenting programme to support parents in
      managing young children's behaviour, a forum for teenagers to socialize and
      access pertinent health information and health days to raise public awareness of
      key community health issues. To date the parenting programme and the youth club
      have been implemented. Evaluation has considered how accessible, appropriate,
      efficient and effective they have been and the knowledge and skills gained by
      participants. This community development demonstrates how health promotion works
      through effective community action.

PMID- 11823732
TI  - Failing to make contact: young men's health.

PMID- 11823733
TI  - Age discrimination is still rife in NHS and social services.

PMID- 11823734
TI  - Nursing home nurse who overlooked her care duties.

PMID- 11823735
TI  - Removal of urinary catheters: midnight vs 0600 hours.
AB  - In the fields of both nursing and medicine there is a dearth of published
      literature on the optimum time to remove indwelling urinary catheters (IDCs)
      following urological surgery. Tradition seems to be in favour of removing IDCs at
      0600 hours despite a lack of evidence to support this practice. This study was
      undertaken to determine whether midnight removal of IDCs resulted in patients'
      resuming normal voiding patterns. A prospective clinical trial was conducted to
      determine the impact midnight removal of urinary catheters would have on the
      patients' voiding pattern, and subsequent discharge from hospital. One hundred
      and sixty patients were entered into the study. The patients were allocated at
      random to have their urinary catheter removed either at midnight or at 0600
      hours. Patients who had their catheters removed at midnight passed a greater
      volume of urine with both their first (268 ml compared with 177 ml; P<0.0001) and
      second voids (322 ml compared with 195 ml; P<0.0001) than their counterparts in
      the 0600 group. This permitted earlier discharge from hospital. The results
      reported in this study support the findings of earlier research that midnight
      removal of IDC leads to an earlier resumption of normal voiding patterns, permits
      earlier discharge from hospital and appears to reduce patients' anxiety. The
      recommendation from this study is that there should be a change in hospital
      policy so that the majority of IDCs are removed at midnight.

PMID- 11823736
TI  - Identifying important issues for people with Parkinson's disease.
AB  - This article identifies issues that are important for people with Parkinson's
      disease (PD). A review of the literature showed that information about PD
      commonly relates to anatomy and physiology, medication and activities of daily
      living. These categories were used to formulate statements on a questionnaire,
      which was distributed to members of the Parkinson's Disease Society within the
      East Midlands. The results demonstrated that those with PD wanted advice on
      maintaining their independence, the amount of movement they were capable of and
      how to respond if their symptoms changed. They wanted to know when to seek
      medical advice, information about their medication and the treatments available
      for PD. Knowing what could be tried next if the present treatment failed was
      thought more important than knowing about all treatments.

PMID- 11823737
TI  - Challenges faced by employees in the home care of elderly people.
AB  - In Finland the care of frail, elderly people is increasingly moving out of
      institutions and into clients' homes. To cope with the challenges, nursing staff
      have to recognize the specific nursing problems involved in home care, as well as
      the most appropriate nursing interventions. The purpose of this study was to
      discover how homecare employees (n=109) perceived the problems involved in the
      home care of elderly people, what they thought were the most relevant nursing
      interventions, and what type of assistance they expected and received in dealing
      with homecare problems. The focus was on homecare problems because they form the
      basis for planning, implementing and evaluating interventions. The data were
      analysed using statistical methods and descriptive statistics. The results showed
      that elderly patients' memory and their cognitive and physical capacity were the
      main sources of problems for homecare employees, defined as registered nurses,
      nursing assistants and home-help personnel. These problems were usually tackled
      by means of nursing interventions, such as memory tests, evaluations of the
      clients' abilities to wash and dress themselves, encouragement of the clients to
      use their existing capacities, and allowing clients sufficient time in care
      situations. The most effective source of assistance to employees was managerial
      supervision and collaboration with co-workers. It is concluded that, in training,
      more attention needs to be paid to support employees' abilities to identify
      nursing problems and to use specific interventions. In-service training and
      clinical supervision should be tailored to address specific problems.

PMID- 11823738
TI  - Discharge of frail older people from acute hospitals across Europe.
AB  - Over the last few years the number of elderly patients in acute hospitals
      throughout Europe has risen dramatically. The pressure on hospital beds leads to
      earlier discharge and the task of sending patients home from hospitals is
      becoming more complex. The provision of health and social services is organized
      in different ways all over Europe. Therefore, it would be of interest to know
      more about how different kinds of systems support the professional carers in
      their effort to satisfy the needs which older people and their significant others
      experience in the discharge process. A pilot study was set up mainly to provide
      information on what kinds of problems are inherent in a multicentre,
      interprofessional research project involving a large number of countries. The
      findings serve as an important knowledge base in a future project. Experiences
      from the pilot study and the benefits of it are presented.

PMID- 11823739
TI  - Outcome measures for erectile dysfunction 2: evaluation.
AB  - This article, the second of two parts, discusses and evaluates the range of
      outcome measures for erectile dysfunction (ED) identified from the literature
      review in part one (Vol 11(1): 54-64). The literature review identified 14
      subjective and 12 objective measures. These outcome measures are needed for the
      components: rigidity, vascular flow, nerve conductivity, intracavernosus muscle
      power, partner satisfaction and quality of life. Instruments selected should
      provide good validity, reliability and responsiveness. Quick, simple, inexpensive
      and efficient outcome measures can be used by nurses.

PMID- 11823740
TI  - Legal aspects of consent 20: research/children/incapable adults.
AB  - James is 10 years old and is suffering from leukaemia. He has had a bone marrow
      transplant which at first appeared to succeed, but has now failed. The health
      authority has refused, in the best interests of James, to fund further
      chemotherapy and a second bone marrow transplant. However, the pioneer of a new
      treatment for leukaemia has offered to provide treatment for James without any
      cost to the family. The family is tempted by the possibility of James' life being
      saved. What is the law?

PMID- 11823741
TI  - High-dependency care: developing a joint surgical recovery unit.
AB  - High-dependency care is a rapidly expanding specialty. The focus of this article
      will be on the joint development between military and NHS staff of a surgical
      recovery unit offering high-dependency care to patients following major surgery.
      Pitfalls, benefits and indicative points to be learnt from this development will
      be identified. In addition, the staff training necessary and learning
      opportunities available will be highlighted. The position of the unit one year
      after opening, and future plans, are outlined. Throughout the development of the
      unit it became clear that an organized, well-established plan of action was
      needed. Staffing must be in place at the earliest opportunity and appropriate
      staff training is essential with adequate support from the relevant areas being
      imperative. Communication is the key to the efficient functioning of the unit. It
      is clear that an area never ceases to develop as the findings of this article
      show. Further collection and auditing of data are essential in the future to
      ensure a useful, viable, quality service.

PMID- 11823742
TI  - Urgotul: alternative to conventional non-adherence dressings.
AB  - This article describes a novel dressing product that was developed from existing
      technology: hydrocolloid. The main benefits of Urgotul relate to the fact that it
      does not adhere to the wound surface, so both wound trauma on removal and the
      build up of moisture under the dressing are avoided.

PMID- 11823743
TI  - Is honesty the best policy?

PMID- 11823744
TI  - Symptom control outcomes in a community palliative care nursing team.
AB  - Measuring outcomes of care is an essential component of clinical governance. This
      article describes a pragmatic approach to auditing symptom control outcomes in a
      community specialist palliative care nursing team. Using a palliative care
      assessment tool, it demonstrates that the team make a positive difference to the
      patient's experience of most symptoms and a plan for further development of
      practice is formulated in response to the results of the audit. Unexpected
      outcomes reveal some of the realities of community specialist palliative care and
      demonstrate that audit is worthwhile despite some of the pitfalls in this area of
      practice.

PMID- 11823745
TI  - Giving voice to the less articulated knowledge of palliative nursing: an
      interpretative study.
AB  - This article details a study that was undertaken in order to give voice and
      thereby increase understanding of the less articulated knowledge used in practice
      by palliative care nurses. An additional aim was to explore perceived influences
      on the development of these nurses. A hermeneutic approach was used to explore
      the lived experiences of seven nurses who had worked in the field for more than 2
      years. The themes that emerged from analysis of the data were: knowing the bigger
      picture, time (movement and measure), ethical dimensions, knowing and minding
      yourself, the 'just' and 'simply' of practice, the embodiment of being with
      unseen tutors. Recommendations relating to the need for further research,
      practice setting and palliative education are suggested from the findings of the
      study.

PMID- 11823746
TI  - 'Living choice': the commitment to tissue donation in palliative care.
AB  - Professionals working in palliative care pride themselves on respecting patients'
      views and wishes. Palliative care patients are often aware that they are going to
      die and so the issue of what is going to happen to them after death becomes more
      relevant. That they should be involved in decisions about tissue donation seems
      obvious, yet many palliative care units do not routinely discuss donation with
      patients and their families. A grounded theory approach was used to develop an
      explanation of the low commitment to tissue donation by palliative care units.
      Six registered nurses and two doctors from each of two separate palliative care
      units participated in semi-structured, audiotaped interviews. Several themes
      emerged from the interviews to form a theory of why there is a low commitment to
      tissue donation in palliative care units. We have called the theory 'living
      choice'. The dominant theme of category was 'patient choice' and this pervaded
      and influenced 'professional role', 'donation process', 'concerns' and
      'knowledge'. All these categories were contained and continuously interacted in
      the palliative care environment.

PMID- 11823747
TI  - Neuro-oncology: a clinical nurse specialist perspective.

PMID- 11823748
TI  - Effective interagency and interprofessional working: facilitators and barriers.
AB  - In the UK the provision of palliative care is not the sole responsibility of the
      National Health Service (NHS); there is an overlap with continuing care, which
      falls within the remit of local authority social services departments. In
      addition, hospice and palliative care services are often considerably dependent
      on charities. Interagency and interdisciplinary working are, therefore, central
      to the successful delivery of palliative care. A multiple (four case) case study
      design was used to explore the provisions of palliative and continuing care. The
      analysis identified the antecedents, structures and processes involved in the
      delivery of interprofessional working, along with the consequences of these in
      either a good model or one where problems were likely to prevail. Individual
      activities, roles and specific service configurations seemed far less significant
      than the overall culture, stability and long-term commitment to a service in a
      given area. Time is required for new service configurations to stabilize so that
      staff are able to overcome barriers and develop the necessary facilitators for
      quality care provision.

PMID- 11823749
TI  - The development of a palliative care-led memorial service in an acute hospital
      setting.
AB  - It is well documented that bereavement is an important function of hospice
      services. However, little data exists that specifically defines the form that
      bereavement support for those whose relatives died in a hospital setting should
      take. This article describes the provision of bereavement support in the form of
      a memorial service for relatives of palliative care patients in an acute
      hospital. It describes the background to its development, highlighting the
      importance of rituals of remembrance, not only for the bereaved but also for the
      staff involved by creating an opportunity for endings. A survey to elicit
      information on memorial services provided by hospital palliative care teams
      elsewhere is discussed, revealing that this service is one of only a few
      provided. The need to engage multidisciplinary support in the organization and
      provision of a memorial service is emphasized, as is the need for formal
      evaluation of such services in order to elicit whether the cultural needs of
      those attending are being met. Recommendations are put forward for future
      investigation, which will inform the ongoing development of subsequent
      bereavement services.

PMID- 11823752
TI  - Centers for education and research on therapeutics report: survey of medication
      errors education during undergraduate and graduate medical education in the
      United States.

PMID- 11823754
TI  - Effects of grapefruit juice on the pharmacokinetics of sildenafil.
AB  - BACKGROUND AND OBJECTIVES: Because of extensive first-pass metabolism, oral
      bioavailability of sildenafil reaches only 40%. Formation of the primary
      metabolite, N -desmethylsildenafil, is mainly mediated by the cytochrome P450
      enzyme CYP3A4. In this study we investigated the influence of grapefruit juice,
      containing inhibitors of intestinal CYP3A4, on the pharmacokinetics of sildenafil
      and N -desmethylsildenafil. METHODS: In a randomized crossover study, 24 healthy
      white male volunteers received single 50-mg doses of sildenafil. Two doses each
      of 250 ml grapefruit juice or water, respectively, were administered 1 hour
      before and together with the drug. Plasma concentrations of sildenafil and N 
      desmethylsildenafil were determined up to 24 hours post dose by use of liquid
      chromatography-tandem mass spectrometry (limit of quantification, 1 ng/ml).
      RESULTS: Grapefruit juice changed the area under the sildenafil plasma
      concentration-time curve from time zero to infinity [AUC(0-infinity) from 620
      [1.53] ng/ml x h to 761 [1.58] ng/ml x h (geometric mean with geometric standard
      deviation), corresponding to a 23% increase (90% confidence interval, 13%-33%). N
      Desmethyl sildenafil AUC(0-infinity) increased by 24% (90% confidence interval,
      17%-32%). Maximum plasma concentrations (C(max)) of sildenafil and N 
      desmethylsildenafil were essentially unchanged. There was a trend toward a
      prolonged time to reach C(max) during the grapefruit juice period (from a median
      of 0.75 hour to a median of 1.13 hours), corresponding to an increase by 0.25
      hour (90% confidence interval, 0-0.63 hour). Interindividual variability was
      pronounced in both periods. CONCLUSIONS: Grapefruit juice increases sildenafil
      bioavailability and tends to delay sildenafil absorption. Sildenafil
      pharmacokinetics may become less predictable with grapefruit juice. Although
      patients usually will not be endangered by concomitant use of grapefruit juice,
      it seems advisable to avoid this combination.

PMID- 11823753
TI  - Fruit juices inhibit organic anion transporting polypeptide-mediated drug uptake
      to decrease the oral availability of fexofenadine.
AB  - OBJECTIVES: Our objective was to examine the effect of different fruits and their
      constituents on P-glycoprotein and organic anion transporting polypeptide (OATP)
      activities in vitro and on drug disposition in humans. METHODS: P-glycoprotein
      mediated digoxin or vinblastine efflux was determined in polarized epithelial
      cell monolayers. OATP-mediated fexofenadine uptake was measured in a transfected
      cell line. The oral pharmacokinetics of 120 mg fexofenadine was assessed with
      water, 25%-strength grapefruit juice, or normal-strength grapefruit, orange, or
      apple juices (1.2 L over 3 hours) in a randomized 5-way crossover study in 10
      healthy subjects. RESULTS: Grapefruit juice and segments and apple juice at 5% of
      normal strength did not alter P-glycoprotein activity. Grapefruit extract reduced
      transport. 6',7'-Dihydroxybergamottin had modest inhibitory activity (50%
      inhibitory concentration [IC(50)], 33 micromol/L). In contrast, grapefruit,
      orange, and apple juices at 5% of normal strength markedly reduced human OATP and
      rat oatp activity. 6',7'-Dihydroxybergamottin potently inhibited rat oatp3 and
      oatp1 (IC(50), 0.28 micromol/L). Other furanocoumarins and bioflavonoids also
      reduced rat oatp3 activity. Grapefruit, orange, and apple juices decreased the
      fexofenadine area under the plasma concentration-time curve (AUC), the peak
      plasma drug concentration (C(max)), and the urinary excretion values to 30% to
      40% of those with water, with no change in the time to reach C(max), elimination
      half-life, renal clearance, or urine volume in humans. Change in fexofenadine AUC
      with juice was variable among individuals and inversely dependent on value with
      water. CONCLUSIONS: Fruit juices and constituents are more potent inhibitors of
      OATPs than P-glycoprotein activities, which can reduce oral drug bioavailability.
      Results support a new model of intestinal drug absorption and mechanism of food
      drug interaction.

PMID- 11823755
TI  - The effects of probenecid on the disposition of risperidone and olanzapine in
      healthy volunteers.
AB  - STUDY DESIGN: The metabolic pathways of most xenobiotics and endogenous compounds
      can be divided into phase 1 (oxidative, reductive, and hydrolytic) and phase 2
      (glucuronidation, sulfate conjugation, glycine and glutathione conjugation, and
      acetylation and methylation) processes. Oxidative metabolism by the cytochrome
      P450 system has been intensively investigated compared with glucuronidation and
      other conjugation pathways. The primary aim of this study was to evaluate the
      disposition of olanzapine or risperidone in healthy volunteers with and without
      coadministration of the uridine diphosphoglucuronate-glucuronosyltransferase
      inhibitor probenecid. We hypothesized that olanzapine disposition would be
      altered as a result of decreased glucuronidation, whereas risperidone disposition
      would be relatively unaffected. METHODS: Our objective was to investigate whether
      this interaction would occur in 12 healthy volunteers, aged 22 to 42 years, who
      participated in a single-dose, randomized, 4-period, double-blind, crossover
      study receiving a single dose of either 5 mg olanzapine or 1 mg risperidone with
      and without 500 mg probenecid (8 doses over 4 days). Multiple blood samples were
      analyzed by means of liquid chromatography-tandem mass spectrometry or HPLC to
      assess the 48-hour time course of risperidone and olanzapine. Urine was assayed
      for free and glucuronidated drugs. RESULTS: When olanzapine was administered with
      probenecid, statistically significant differences were observed between plasma
      pharmacokinetic parameters compared with olanzapine administered alone (maximum
      concentration, P <.05; area under the plasma concentration-time curve from time
      zero to 24 hours, P <.01). Clearance was not significantly different between the
      treatment phases. Risperidone pharmacokinetic parameters were not significantly
      different (all parameters, P >.05). CONCLUSION: Inhibition of uridine
      diphosphoglucuronate-glucuronosyltransferase appeared to influence the
      disposition of olanzapine but not risperidone. Phase 2 metabolism may
      significantly influence the disposition of antipsychotic drugs and may be an
      important aspect of the variability in metabolism, participation in drug-drug
      interactions, and clinical response to some antipsychotic agents.

PMID- 11823756
TI  - Pharmacokinetics of betamethasone in twin and singleton pregnancy.
AB  - OBJECTIVE: The aims of the study were to compare the pharmacokinetics of
      betamethasone in singleton pregnancy with the pharmacokinetics in twin pregnancy
      and to assess the adrenal suppression produced by betamethasone. STUDY DESIGN: We
      measured serial betamethasone and cortisol levels in 30 singleton and 21 twin
      pregnancies after the first dose of betamethasone and calculated the
      pharmacokinetic parameters for betamethasone including volume of distribution,
      half-life, and clearance. We also measured cord and maternal blood levels of
      betamethasone at the birth of infants of 13 singleton and 9 twin pregnancies.
      RESULTS: The half-life of betamethasone in mothers with twin pregnancies was
      significantly shorter than that in mothers with singleton pregnancies (7.2 +/-2.4
      versus 9.0 +/- 2.7 hours; P <.017). Clearance of betamethasone in the twin
      pregnancies appeared greater than in singleton pregnancies (8.4 +/- 6.4 versus
      5.7+/- 3.1 L/h; P =.06) but did not reach statistical significance. Volume of
      distribution was similar in the two groups. Because the time between the last
      dose of betamethasone and birth varied widely (range, 2-158 hours), mothers with
      a longer interval after treatment tended to have a higher cord-to-maternal
      betamethasone ratio than did mothers with a shorter interval in both twin and
      singleton pregnancies. This finding indicated delayed fetal clearance, but the
      correlation was weak (R (2) = 0.29 for twins and 0.08 for singletons).
      CONCLUSION: The shorter half-life of betamethasone in twin pregnancy than in
      singleton pregnancy may cause the level of betamethasone to be subtherapeutic for
      lung maturation in twin pregnancy.

PMID- 11823757
TI  - Effect of modafinil on the pharmacokinetics of ethinyl estradiol and triazolam in
      healthy volunteers.
AB  - BACKGROUND: Modafinil has been reported to produce a concentration-related
      induction of CYP3A4/5 activity in vitro in primary cultures of human hepatocytes.
      OBJECTIVE: Our objective was to determine whether the pharmacokinetics of steady
      state ethinyl estradiol (INN, ethinylestradiol) and single-dose triazolam were
      altered after 4 weeks of modafinil treatment in volunteers. METHODS: This was a
      placebo-controlled, single-blind, single-period study in 41 female subjects who
      were receiving long-term treatment with an oral contraceptive that contained
      ethinyl estradiol (0.035 mg) and norgestimate (0.180-0.250 mg). Pharmacokinetic
      profiles for ethinyl estradiol and for a single oral dose of triazolam (0.125 mg)
      were obtained the day before initiation of treatment with modafinil (200 mg for 7
      days, followed by 400 mg for 21 days) or placebo (28 days). A second dose of
      triazolam was administered with the final dose of modafinil, and pharmacokinetic
      profiling was repeated. RESULTS: The modafinil treatment group had a marked
      decrease in maximum observed plasma concentrations and areas under the plasma
      concentration-time curve for triazolam relative to placebo, with a much smaller
      decrease in these parameters for ethinyl estradiol. The half-life of triazolam
      was also decreased, but the half-life of ethinyl estradiol did not appear to be
      affected by treatment with modafinil. CONCLUSION: Modafinil induced CYP3A4/5
      activity in humans in vivo, suggesting that there is potential for metabolic drug
      drug interactions between modafinil and substrates of CYP3A4/5. However, the
      induction appeared to be more gastrointestinal than hepatic in nature. Therefore
      significant metabolic drug-drug interactions are most likely to occur with
      compounds (such as triazolam) that undergo significant gastrointestinal CYP3A4/5
      mediated first-pass metabolism.

PMID- 11823758
TI  - The influence of efavirenz on the pharmacokinetics of a twice-daily combination
      of indinavir and low-dose ritonavir in healthy volunteers.
AB  - OBJECTIVE: This study evaluated the effect of multiple-dose efavirenz on the
      steady-state pharmacokinetics of the combination of indinavir (800 mg) and low
      dose ritonavir (100 mg) twice a day, in which ritonavir is used to increase
      indinavir plasma concentrations. METHODS: Eighteen healthy male volunteers
      participated in this multiple-dose, 1-arm, 2-period interaction study. They took
      a combination of 800 mg indinavir and 100 mg ritonavir with food for 15 days.
      From days 15 to 29, a once-daily administration of 600 mg efavirenz was added to
      the combination. Pharmacokinetics of indinavir and ritonavir on days 15 and 29
      were compared. RESULTS: Fourteen volunteers completed the study. The addition of
      efavirenz resulted in significant reductions (P <.01) in indinavir area under the
      curve (AUC, -25%), trough concentration (C(min), -50%), and maximum concentration
      (C(max), -17%). All indinavir C(min) levels on day 29 remained equivalent to or
      above the mean C(min) value described for the regimen of 800 mg indinavir three
      times a day, without ritonavir (0.15 mg/L). Changes in ritonavir AUC, C(min), and
      C(max) were -36%, -39%, and -34%, respectively. Pharmacokinetics of efavirenz on
      day 29 were comparable with published data. CONCLUSIONS: The addition of
      efavirenz to a combination of 800 mg indinavir and 100 mg ritonavir twice daily
      results in significant decreases in AUC, C(max), and especially C(min) of
      indinavir. The dose of indinavir or ritonavir should be increased to maintain
      similar indinavir drug levels after addition of efavirenz to the indinavir
      ritonavir combination. Dose modifications may not be needed in antiretroviral
      naive human immunodeficiency virus-infected patients if the reference C(min) of
      the regimen of 800 mg indinavir 3 times a day is considered to be adequate.

PMID- 11823759
TI  - Comparative angiotensin II receptor blockade in healthy volunteers: the
      importance of dosing.
AB  - OBJECTIVES: We have reported previously that 80 mg valsartan and 50 mg losartan
      provide less receptor blockade than 150 mg irbesartan in normotensive subjects.
      In this study we investigated the importance of drug dosing in mediating these
      differences by comparing the AT(1)-receptor blockade induced by 3 doses of
      valsartan with that obtained with 3 other antagonists at given doses. METHODS:
      Valsartan (80, 160, and 320 mg), 50 mg losartan, 150 mg irbesartan, and 8 mg
      candesartan were administered to 24 healthy subjects in a randomized, open-label,
      3-period crossover study. All doses were given once daily for 8 days. The
      angiotensin II receptor blockade was assessed with two techniques, the reactive
      rise in plasma renin activity and an in vitro radioreceptor binding assay that
      quantified the displacement of angiotensin II by the blocking agents.
      Measurements were obtained before and 4 and 24 hours after drug intake on days 1
      and 8. RESULTS: At 4 and 24 hours, valsartan induced a dose-dependent "blockade"
      of AT(1) receptors. Compared with other antagonists, 80 mg valsartan and 50 mg
      losartan had a comparable profile. The 160-mg and 320-mg doses of valsartan
      blocked AT(1) receptors at 4 hours by 80%, which was similar to the effect of 150
      mg irbesartan. At trough, however, the valsartan-induced blockade was slightly
      less than that obtained with irbesartan. With use of plasma renin activity as a
      marker of receptor blockade, on day 8, 160 mg valsartan was equivalent to 150 mg
      irbesartan and 8 mg candesartan. CONCLUSIONS: These results show that the
      differences in angiotensin II receptor blockade observed with the various AT(1)
      antagonists are explained mainly by differences in dosing. When 160-mg or 320-mg
      doses were investigated, the effects of valsartan hardly differed from those
      obtained with recommended doses of irbesartan and candesartan.

PMID- 11823760
TI  - The African-specific CYP2D617 allele encodes an enzyme with changed substrate
      specificity.
AB  - OBJECTIVE: The effects of the CYP2D6*17 and *29 alleles on substrate specificity
      and enzyme activity were studied by correlating CYP2D6 genotype to phenotype with
      4 probe drugs (codeine, debrisoquine, dextromethorphan, metoprolol) in black
      Tanzanians and white Swedes. METHODS: The black Tanzanian subjects represented
      the following 6 genotypic groups: A, (CYP2D6*1 or *2)/(*1 or *2) (n = 13); B,
      CYP2D6*17 /*17 (n = 5); C, CYP2D6*29 /*29 (n = 4); D, CYP2D6*1 /*17 (n = 5); E,
      CYP2D6*5/*17 (n = 4); and F, various genotypes (n = 4). The white subjects were
      from 4 groups, as follows: A, (CYP2D6*1 or *2)/(*1 or *2) (n = 7); B, (CYP2D6*1
      or *2)/(*3, *4, or *5) (n = 7); C, homozygous for defect alleles (n = 7); and D,
      duplicated CYP2D6 gene (n = 2). RESULTS: The metabolic ratios of the 4 probe
      drugs correlated significantly (r (s) = 0.69-0.92; P <.001) in both populations.
      Tanzanian subjects homozygous for the CYP2D6*17 allele were slower metabolizers
      when debrisoquine or dextromethorphan was used as the probe drug than when
      codeine or metoprolol was used, showing a different substrate specificity of
      CYP2D6.17 than of CYP2D6.1 and CYP2D6.2. This was confirmed with analysis of
      covariance of the different metabolic ratios for a subgroup of subjects carrying
      only the CYP2D6*17 mutated allele (n = 9) compared with all other subjects (n =
      44). The metabolic ratios of dextromethorphan and metoprolol differed
      significantly among Tanzanian subjects homozygous for the CYP2D6*29 allele
      compared with those with CYP2D6*1 or *2 alleles. CONCLUSION: We found differences
      in the disposition of 4 CYP2D6 probe drugs in black Tanzanians compared with
      Swedes. The differences were caused by the presence of CYP2D6.17 and CYP2D6.29.
      The results show that CYP2D6.17 exhibits altered substrate specificity compared
      with CYP2D6.1 and CYP2D6.2.

PMID- 11823761
TI  - Pharmacokinetics of losartan and its metabolite E-3174 in relation to the CYP2C9
      genotype.
AB  - BACKGROUND AND AIM: Losartan is metabolized by polymorphic CYP2C9 to E-3174. Our
      aim was to evaluate the pharmacokinetics of losartan and E-3174 in relation to
      the CYP2C9 genotype. METHODS: A 50-mg oral dose of losartan was given to 22
      Swedish volunteers with different CYP2C9 genotypes. Losartan and E-3174 were
      analyzed by HPLC in plasma and urine samples collected up to 24 hours after drug
      intake. Furthermore, losartan and E-3174 were analyzed in 8-hour urine samples
      collected from 17 Spanish subjects after a single oral dose of 25 mg losartan.
      RESULTS: The maximum plasma concentration of E-3174 was significantly (P <.05)
      lower in the CYP2C9*1/*3 (n = 5) and CYP2C9*2/*3 (n = 4) groups compared with the
      CYP2C9*1/*1 (n = 6) and CYP2C9*1/*2 (n = 3) groups and extremely low in 1 subject
      with the CYP2C9*3/*3 genotype. The ratio of the total losartan area under the
      plasma concentration-time curve (AUC) to the total E-3174 AUC
      (AUC(losartan)/AUC(E-3174)) was higher in the subject with the CYP2C9*3/*3
      genotype (30-fold) and also in the CYP2C9*1/*3 and *2/*3 groups (approximately 2-
      and 3-fold, respectively) compared with the CYP2C9*1/*1 group. The plasma ratios
      correlated significantly with the 0- to 8-hour urinary losartan/E-3174 ratios.
      Among the total of 39 subjects, the urinary ratio was significantly higher in
      subjects with the CYP2C9*1/*3 (n = 10) and *2/*3 (n = 4) genotypes than in those
      with the CYP2C9*1/*1 genotype (n = 11; P <.01) and approximately 40-fold higher
      in subjects with the CYP2C9*3/*3 genotype (n = 3). CONCLUSION: The CYP2C9*3
      allele was shown to be associated with decreased formation of E-3174 from
      losartan. The significant differences between genotypes in plasma and urine
      losartan/E-3174 ratios and the good correlation between the plasma and urine
      ratios suggest that the losartan/E-3174 ratio in 0- to 8-hour urine specimens may
      serve as a phenotyping assay for CYP2C9 activity. Further studies in larger
      populations will be required to establish this.

PMID- 11823762
TI  - Use of a spontaneous adverse drug events database for identification of
      unanticipated drug benefits.
AB  - We describe an examination of a spontaneous adverse events database in an effort
      to identify agents with possible hitherto unknown antiangiogenic properties. The
      surrogate end point was abnormal wound healing. This analysis represents use of
      this database for identification of a possibly useful in vivo side effect.
      Through thoughtful choice of end points, we believe spontaneous adverse events
      databases have the capacity for hypothesis generation in a search for
      unanticipated beneficial drug properties.

PMID- 11823763
TI  - A modern pharmaceutical company.

PMID- 11823764
TI  - Harpagophytum extracts.

PMID- 11823765
TI  - Persistence of delays in presentation and treatment for patients with acute
      myocardial infarction: The GUSTO-I and GUSTO-III experience.
AB  - STUDY OBJECTIVE: Early treatment with fibrinolytic therapy substantially
      decreases mortality in acute myocardial infarction (AMI). We examined delays to
      hospital arrival and treatment in 2 large, multinational, randomized trials of
      fibrinolytic therapy: Global Utilization of Streptokinase and Tissue Plasminogen
      Activator for Occluded Coronary Arteries (GUSTO-I) and Global Use of Strategies
      to Open Occluded Coronary Arteries (GUSTO-III). METHODS: We evaluated delays to
      hospital arrival, time from arrival to treatment, and total time to treatment in
      the 27,849 US patients with AMI enrolled in GUSTO-I or GUSTO-III. Time intervals
      were defined prospectively for total time to treatment and symptom onset to
      hospital arrival as 0 to 2 hours (early), 2 to 4 hours, or more than 4 hours
      (late). Time to fibrinolytic therapy once in hospital was prospectively defined
      as 0 to 1 hour (early) or more than 1 hour (late). Socioeconomic data were also
      obtained from patients enrolled in the GUSTO-III trial. RESULTS: In GUSTO-III, as
      in GUSTO-I, patients who arrived at the hospital later were older (64 years
      versus 60 years; P =.001) and more often female (35% versus 27%; P =.001), black
      (6% versus 4%; P =.02), and diabetic (25% versus 16%; P =.001). These groups also
      received treatment later once in hospital, as did patients with hypertension (48%
      versus 42%; P =.001), previous angina (46% versus 36%; P =.001), and previous
      infarction (21% versus 16%; P =.001). Higher levels of education, professional
      occupations, and private health insurance were associated with significantly
      earlier arrival and treatment. Although in hospital time to treatment has
      decreased (66 minutes to 48 minutes; P <.0001), time to arrival has not changed
      over the past 7 years, averaging 84 minutes. CONCLUSION: Certain groups of
      patients with AMI, including the elderly, women, diabetic patients, and
      minorities, exhibit delays to hospital arrival and treatment in the emergency
      setting. Patients with higher educational levels, professional occupations, and
      private health insurance arrive at the hospital sooner and receive treatment more
      quickly. Patients and health care providers must be educated regarding high-risk
      populations for delay to maximize benefit from fibrinolytic therapy.

PMID- 11823766
TI  - B-type natriuretic peptide predicts future cardiac events in patients presenting
      to the emergency department with dyspnea.
AB  - STUDY OBJECTIVE: B-Type natriuretic peptide (BNP) is a neurohormone secreted from
      the cardiac ventricles in response to volume expansion and pressure overload. We
      have recently demonstrated that BNP can differentiate congestive heart failure
      (CHF) from other causes of dyspnea in patients presenting to the emergency
      department. In this study, we assess whether BNP levels drawn in patients
      presenting with dyspnea to the ED were a predictor of future cardiac events.
      METHODS: In 325 patients presenting with dyspnea to the ED, BNP levels were
      determined. Patients were then followed up for 6 months to determine the
      following end points: death (cardiac and noncardiac), hospital admissions
      (cardiac), and repeat ED visits for CHF. Receiver operating characteristic (ROC)
      curves, relative risks (RRs), and Kaplan-Meier plots were used to assess the
      ability of BNP levels to predict future cardiac events. RESULTS: The area under
      the ROC curve using BNP to detect a CHF end point-a CHF death, hospital
      admission, or repeat ED visit-was 0.870 (95% confidence interval [CI] 0.826 to
      0.915). A BNP value of 480 pg/mL had a sensitivity of 68%, specificity of 88%,
      and an accuracy of 85% for predicting a subsequent CHF end point. The area under
      the ROC curve using BNP to detect death from CHF was 0.881 (95% CI 0.807 to
      0.954) and for any cardiac death was 0.877 (95% CI 0.822 to 0.933). BNP was not
      associated with death from noncardiac causes. Using Kaplan-Meier plots for all
      CHF events, rising BNP levels were associated with a progressively worse
      prognosis. Patients with BNP levels more than 480 pg/mL had a 51% 6-month
      cumulative probability of a CHF event. Alternatively, patients with BNP levels
      less than 230 pg/mL had an excellent prognosis with only 2.5% incidence of CHF
      end points. The RR of 6-month CHF death in patients with BNP levels more than 230
      pg/mL was 24.1. The RR of 6-month noncardiac death with BNP levels more than 230
      pg/mL was 1.1. BNP levels were also predictive of CHF events in subsets of
      patients with positive CHF histories and ED diagnoses. CONCLUSION: In this study
      population, BNP levels measured in patients presenting with dyspnea to the ED are
      highly predictive of cardiac events over the next 6 months.

PMID- 11823767
TI  - A randomized, controlled trial of panic disorder treatment initiation in an
      emergency department chest pain center.
AB  - STUDY OBJECTIVE: We examine the effect of a protocol for panic disorder
      recognition and treatment initiation on medication initiation rates and
      medication continuation rates at 1- and 3-month follow-up. METHODS: Enrolled
      participants, all at low to moderate risk for acute coronary syndrome, completed
      a 6-hour emergency department chest pain evaluation and panic disorder screen.
      Participants who had results positive for panic disorder completed the Panic
      Disorder Module of the Structured Clinical Interview (SCID) for the Diagnostic
      and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) by the
      research psychiatrist and the treating emergency physician, each blinded to the
      other's rating. Participants with panic disorder were randomized to either
      paroxetine initiation at 20 mg/d for 1 month or usual care with telephone follow
      up at 3 months. RESULTS: Fifty (32%) of 156 enrolled participants met criteria
      for panic disorder. All 25 (100%) participants in the paroxetine group initiated
      treatment, compared with 6 (24%) in the usual care group initiating any form of
      treatment (P =.006, relative risk [RR] 2.58, 95% confidence interval [CI] 1.20 to
      5.58). Fourteen (56%) participants continued paroxetine treatment for at least 1
      month, and at 3 months, 9 (36%) continued on some antipanic medication, compared
      with 2 (8%) for the usual care group (P =.05, RR 3.57, 95% CI 0.84 to 15.8).
      CONCLUSION: Panic disorder is common and severe in this sample of patients with
      chest pain. A screening measure and a brief (5-minute) structured interview
      allowed emergency physicians with no extra training to reliably diagnose panic
      disorder and initiate pharmacologic treatment.

PMID- 11823768
TI  - Criteria for the safe use of D-dimer testing in emergency department patients
      with suspected pulmonary embolism: a multicenter US study.
AB  - STUDY OBJECTIVE: We derive a decision rule to partition emergency department
      patients with suspected pulmonary embolism (PE) into a small, high-risk group
      (>40% pretest probability) that is unsafe for D -dimer testing and a larger group
      that is safe to have PE ruled out with either a whole-blood D -dimer plus
      alveolar deadspace measurement or a quantitative D -dimer assay. METHODS: Nine
      hundred thirty-four patients with suspected PE were studied at 7 urban EDs in the
      United States. Patients were prospectively interviewed and examined for
      recognized symptoms, signs, and risk factors associated with PE. These data were
      collected before standard objective imaging for PE. Selected variables were
      analyzed by multivariate logistic analysis to determine factors associated with
      PE (P <.05). A decision rule was then constructed to categorize approximately 80%
      of ED patients as safe for D -dimer testing. RESULTS: Pretest prevalence of PE
      was 19.4% (181/934; 95% confidence interval [CI] 16.3% to 21.7%). Six variables
      found to be significant on multivariate analysis were used to construct the
      decision rule. Unsafe patients had either a shock index (heart rate/systolic
      blood pressure) more than 1.0 or age older than 50 years, together with any one
      of the following conditions: unexplained hypoxemia (SaO (2) <95%; no prior lung
      disease), unilateral leg swelling, recent major surgery, or hemoptysis. These
      criteria were met by 197 (21.0%) of 934 patients, and 83 of 197 (42.1%; 95% CI
      35.3% to 49.6%) patients had PE. Exclusion of these 197 unsafe patients
      significantly decreased the probability of PE in the remaining 737 (79.0%) safe
      patients to 13.3% (95% CI 10.9% to 15.9%). CONCLUSION: Simple clinical criteria
      can permit safe D -dimer testing in the majority of ED patients with suspected
      PE. These criteria warrant prospective validation.

PMID- 11823769
TI  - How relevant are the systematic reviews in the cochrane library to emergency
      medical practice?
AB  - STUDY OBJECTIVES: The Cochrane Database of Systematic Reviews (CDSR), one of the
      databases in the Cochrane Library, is a compilation of regularly updated
      systematic reviews with meta-analytic summary statistics. We conducted a study of
      the CDSR to evaluate the relevance of this database to emergency medical
      practice. METHODS: Using criteria that were determined a priori, 2 reviewers
      independently screened the titles of 795 completed reviews from the April 2000
      CDSR for possible relevance to emergency medicine practice. Five reviewers
      independently ranked summaries of these reviews for degree of relevance.
      Agreement was measured using kappa statistics. Disagreements were resolved by
      consensus or adjudication. RESULTS: Screening of 795 completed reviews identified
      136 (17%) as "possibly" and 151 (19%) as "likely" relevant (simple agreement,
      74%; kappa=0.82). Further independent assessment indicated 95 (12%) of the 151
      "likely" systematic reviews were directly relevant to emergency medicine
      practice, whereas 44 (6%) were indirectly relevant (simple agreement, 77%;
      kappa=0.45). Cochrane Review Groups producing the most emergency medicine
      relevant systematic reviews included acute respiratory infections (14 [10%]),
      injuries (14 [10%]), pregnancy and childbirth (13 [10%]), stroke (12 [10%]), and
      airways (11 [8%]). In contrast, only 1 (0.1%) of the reviews produced by the
      Heart Review Group was considered directly relevant to emergency medicine
      practice. CONCLUSION: More than one third of CDSR reviews have some relevance,
      and 12% are directly relevant, to emergency medical practice or discharge
      planning. Although certain conditions are well covered, other key emergency
      medicine areas are not. Emergency physicians should consider the Cochrane Library
      an important evidence-based resource for emergency medicine therapeutic
      interventions and should examine ways of increasing the number of reviews
      relevant to emergency medicine.

PMID- 11823770
TI  - Analysis of pediatric hospitalizations after emergency department release as a
      quality improvement tool.
AB  - STUDY OBJECTIVE: We characterize repeat pediatric emergency department visits and
      determine the cause for such visits as an indicator of potential need for quality
      improvement. We hypothesized that most repeat ED visits resulting in
      hospitalization do not represent medical errors. METHODS: The study was performed
      at a large, tertiary care, academic children's hospital. Patients who returned to
      the ED within 72 hours of a previous visit were identified by computerized
      registration data. The charts of these patients were then reviewed by a member of
      the ED medical staff to identify factors from the initial visit that contributed
      to the return visit. A multidisciplinary committee then reviewed each case until
      consensus was achieved regarding the cause for the repeat visit. In this study,
      we analyzed the quality improvement decisions from a 12-month period. RESULTS:
      Over a 12-month period, during which there were a total of 51,195 visits, 285
      (0.56%) patients were hospitalized after a repeat visit. The repeat visit was
      determined to be unrelated to the first visit in 12 (4.2%) patients. In 12 (4.2%)
      cases, the cause for repeat visit and hospitalization could not be determined.
      This resulted in a total of 261 patients for analysis. In 234 (90.0%) patients,
      the return visit was determined to be a result of the progression of illness (no
      medical error). Ten (3.8%) patients had a missed diagnosis, whereas 2 (0.8%)
      patients had errors in their treatment (likely medical error). An incomplete
      workup was cited in 7 (2.7%) patients (potential medical error). Parenting
      factors (refusing admission, not filling prescriptions, not giving prescribed
      medications) were noted in 5 (1.9%) cases. Three (1.1%) patients did not follow
      up with appropriate subspecialists. CONCLUSION: The overall rate of repeat visits
      resulting in hospitalization is small. In the majority of these cases (90.0%),
      the ED evaluation was appropriate and the admission was for progression of the
      patient's illness. Given the small number of patients and the infrequency of
      missed diagnoses, this may not be an efficient method for assessing ED
      performance.

PMID- 11823771
TI  - Cardiology and emergency medicine: united we stand, divided we fall.

PMID- 11823772
TI  - Rapid process redesign in a university-based emergency department: decreasing
      waiting time intervals and improving patient satisfaction.
AB  - Academic emergency departments are traditionally associated with inefficiency and
      long waits. The academic medical model presents unique barriers to system
      changes. Several non-university-based EDs have undertaken process redesign, with
      significant decreases in patient waiting time intervals. This is the presentation
      of a rapid process redesign in a university-based ED to reduce waiting time
      intervals. We present the application of a process-improvement team approach to
      evaluate and redesign patient flow. As a result of this effort, the median
      waiting room time interval (triage to patient room) decreased from 31 minutes in
      January 1998 to 4 minutes in July 1998. ED throughput times also decreased, from
      4 hours, 21 minutes in January 1998 to 2 hours, 55 minutes in July 1998. Urgent
      care waiting room time intervals decreased from 52 minutes to 7 minutes and
      throughput times from 2 hours, 9 minutes to 1 hour, 10 minutes. Patient
      satisfaction evaluations by an independent institute demonstrated dramatic
      improvement and establishment of a new benchmark for academic EDs. Process
      redesign is possible in a busy, complex, tertiary-care ED, with decreases in
      waiting time intervals and improvement in patient satisfaction. Major sustained
      support from top-level hospital administrators and physician leadership are
      fundamental prerequisites. With these in place, a process improvement team
      approach for evaluating and redesigning the patient care system can be
      successful.

PMID- 11823773
TI  - Evidence-based emergency medicine. Online evidence-based emergency medicine.

PMID- 11823774
TI  - Evidence-based emergency medicine. Predicting the future: can this patient with
      acute congestive heart failure be safely discharged from the emergency
      department?

PMID- 11823775
TI  - Evidence-based emergency medicine. Feedback: computed tomography and lumbar
      puncture for the diagnosis of subarachnoid hemorrhage: the importance of accurate
      interpretation.

PMID- 11823777
TI  - Recent trends in motorcycle fatalities.

PMID- 11823778
TI  - Riding off into the sunset: Implications of an aging motorcyclist population.

PMID- 11823779
TI  - Ash wednesday.

PMID- 11823780
TI  - Afghan refugees: the ugly truth.

PMID- 11823781
TI  - Whither psychiatry?

PMID- 11823782
TI  - Severe acute valproic acid intoxication successfully treated with
      hemodiafiltration without hemoperfusion.

PMID- 11823783
TI  - Asymptomatic traumatic tricuspid regurgitation: a case report with an early
      diagnosis.

PMID- 11823784
TI  - Ventricular fibrillation after pseudo-Bartter's syndrome.

PMID- 11823785
TI  - Activation-induced cytidine deaminase turns on somatic hypermutation in
      hybridomas.
AB  - The production of high-affinity protective antibodies requires somatic
      hypermutation (SHM) of the antibody variable (V)-region genes. SHM is
      characterized by a high frequency of point mutations that occur only during the
      centroblast stage of B-cell differentiation. Activation-induced cytidine
      deaminase (AID), which is expressed specifically in germinal-centre centroblasts,
      is required for this process, but its exact role is unknown. Here we show that
      AID is required for SHM in the centroblast-like Ramos cells, and that expression
      of AID is sufficient to induce SHM in hybridoma cells, which represent a later
      stage of B-cell differentiation that does not normally undergo SHM. In one
      hybridoma, mutations were exclusively in G*C base pairs that were mostly within
      RGYW or WRCY motifs, suggesting that AID has primary responsibility for mutations
      at these nucleotides. The activation of SHM in hybridomas indicates that AID does
      not require other centroblast-specific cofactors to induce SHM, suggesting either
      that it functions alone or that the factors it requires are expressed at other
      stages of B-cell differentiation.

PMID- 11823786
TI  - Excitatory glycine receptors containing the NR3 family of NMDA receptor subunits.
AB  - The N-methyl-D-aspartate subtype of glutamate receptor (NMDAR) serves critical
      functions in physiological and pathological processes in the central nervous
      system, including neuronal development, plasticity and neurodegeneration.
      Conventional heteromeric NMDARs composed of NR1 and NR2A-D subunits require dual
      agonists, glutamate and glycine, for activation. They are also highly permeable
      to Ca2+, and exhibit voltage-dependent inhibition by Mg2+. Coexpression of NR3A
      with NR1 and NR2 subunits modulates NMDAR activity. Here we report the cloning
      and characterization of the final member of the NMDAR family, NR3B, which shares
      high sequence homology with NR3A. From in situ and immunocytochemical analyses,
      NR3B is expressed predominantly in motor neurons, whereas NR3A is more widely
      distributed. Remarkably, when co-expressed in Xenopus oocytes, NR3A or NR3B co
      assembles with NR1 to form excitatory glycine receptors that are unaffected by
      glutamate or NMDA, and inhibited by D-serine, a co-activator of conventional
      NMDARs. Moreover, NR1/NR3A or -3B receptors form relatively Ca2+-impermeable
      cation channels that are resistant to Mg2+, MK-801, memantine and competitive
      antagonists. In cerebrocortical neurons containing NR3 family members, glycine
      triggers a burst of firing, and membrane patches manifest glycine-responsive
      single channels that are suppressible by D-serine. By itself, glycine is normally
      thought of as an inhibitory neurotransmitter. In contrast, these NR1/NR3A or -3B
      'NMDARs' constitute a type of excitatory glycine receptor.

PMID- 11823787
TI  - Understanding quantitative genetic variation.
AB  - Until recently, it was impracticable to identify the genes that are responsible
      for variation in continuous traits, or to directly observe the effects of their
      different alleles. Now, the abundance of genetic markers has made it possible to
      identify quantitative trait loci (QTL)--the regions of a chromosome or, ideally,
      individual sequence variants that are responsible for trait variation. What kind
      of QTL do we expect to find and what can our observations of QTL tell us about
      how organisms evolve? The key to understanding the evolutionary significance of
      QTL is to understand the nature of inherited variation, not in the immediate
      mechanistic sense of how genes influence phenotype, but, rather, to know what
      evolutionary forces maintain genetic variability.

PMID- 11823788
TI  - The use of molecular genetics in the improvement of agricultural populations.
AB  - Substantial advances have been made in the genetic improvement of agriculturally
      important animal and plant populations through artificial selection on
      quantitative traits. Most of this selection has been on the basis of observable
      phenotype, without knowledge of the genetic architecture of the selected
      characteristics. However, continuing molecular genetic analysis of traits in
      animal and plant populations is leading to a better understanding of quantitative
      trait genetics. The genes and genetic markers that are being discovered can be
      used to enhance the genetic improvement of breeding stock through marker-assisted
      selection.

PMID- 11823789
TI  - Rat genetics: attaching physiology and pharmacology to the genome.
AB  - During the past five years, the Rat Genome Project has been rapidly gaining
      momentum, especially since the announcement in August 2000 of plans to sequence
      the rat genome. Combined with the wealth of physiological and pharmacological
      data for the rat, the genome sequence should facilitate the discovery of
      mammalian genes that underlie the physiological pathways that are involved in
      disease. Most importantly, this combined physiological and genomic information
      should also lead to the development of better pre-clinical models of human
      disease, which will aid in the development of new therapeutics.

PMID- 11823790
TI  - Mapping and analysis of quantitative trait loci in experimental populations.
AB  - Simple statistical methods for the study of quantitative trait loci (QTL), such
      as analysis of variance, have given way to methods that involve several markers
      and high-resolution genetic maps. As a result, the mapping community has been
      provided with statistical and computational tools that have much greater power
      than ever before for studying and locating multiple and interacting QTL. Apart
      from their immediate practical applications, the lessons learnt from this
      evolution of QTL methodology might also be generally relevant to other types of
      functional genomics approach that are aimed at the dissection of complex
      phenotypes, such as microarray assessment of gene expression.

PMID- 11823791
TI  - Medaka--a model organism from the far East.
AB  - Genome sequencing has yielded a plethora of new genes the function of which can
      be unravelled through comparative genomic approaches. Increasingly, developmental
      biologists are turning to fish as model genetic systems because they are amenable
      to studies of gene function. Zebrafish has already secured its place as a model
      vertebrate and now its Far Eastern cousin--medaka--is emerging as an important
      model fish, because of recent additions to the genetic toolkit available for this
      organism. Already, the popularity of medaka among developmental biologists has
      led to important insights into vertebrate development.

PMID- 11823792
TI  - Segmental duplications and the evolution of the primate genome.
AB  - Initial human genome sequence analysis has revealed large segments of nearly
      identical sequence in particular chromosomal regions. The recent origin of these
      segments and their abundance (approximately 5%) has challenged investigators to
      elucidate their underlying mechanism and role in primate genome evolution.
      Although the precise fraction is unknown, some of these duplicated segments have
      recently been shown to be associated with rapid gene innovation and chromosomal
      rearrangement in the genomes of man and the great apes.

PMID- 11823793
TI  - No post-genetics era in human disease research.
AB  - In the 1980s, linkage emerged as a route to discovering genetic defects, spurring
      the rise of genomics and making gene-based approaches available to previously
      phenotype-orientated researchers. In the post-genomics era, genetics is
      fundamental to understanding disease at all stages of the pathogenic process.

PMID- 11823794
TI  - Sibling rivalry in the E2F family.
AB  - The E2F transcription factor family determines whether or not a cell will divide
      by controlling the expression of key cell-cycle regulators. The individual E2Fs
      can be divided into distinct subgroups that act in direct opposition to one
      another to promote either cellular proliferation or cell-cycle exit and terminal
      differentiation. What is the underlying molecular basis of this 'push-me-pull
      you' regulation, and what are its biological consequences?

PMID- 11823795
TI  - Mechanisms of transcription-coupled DNA repair.
AB  - Several types of helix-distorting DNA lesions block the passage of elongating RNA
      polymerase II. Surprisingly, such transcription-blocking lesions are usually
      repaired considerably faster than non-obstructive lesions in the non-transcribed
      strand or in the genome overall. In this review, our knowledge of eukaryotic
      transcription-coupled repair (TCR) will be considered from the point of view of
      transcription, and current models for the mechanism of TCR will be discussed.

PMID- 11823796
TI  - MAPK-regulated transcription: a continuously variable gene switch?
AB  - Switching mechanisms that control genes could be viewed either as stable binary
      switches, in which genes exist in 'on' or 'off' states; or as quantitative
      rheostat-like switches, in which the rate of transcription is continuously
      variable and coupled directly to the strength of intracellular signalling events.
      Here, we discuss the biological need for quantitative gene regulation and, using
      mitogen-activated protein kinase (MAPK)-controlled transcription as a model,
      assess the evidence for its existence and postulate mechanisms by which it might
      occur.

PMID- 11823797
TI  - Mammalian transcription factors in yeast: strangers in a familiar land.
AB  - Many transcription factors in human cells have functional orthologues in yeast,
      and a common experimental theme has been to define the function of the yeast
      protein and then test whether the mammalian version behaves similarly. Although,
      at first glance, this approach does not seem feasible for factors that do not
      have yeast counterparts, mammalian transcriptional activators or repressors can
      be expressed directly in yeast. Often, the mammalian factor retains function in
      yeast, and this allows investigators to exploit the experimental tractability of
      yeast to ask a diverse set of questions.

PMID- 11823799
TI  - Thomas Henry Huxley's developmental view of the cell.
AB  - In 1853, the British physiologist Thomas Henry Huxley roundly criticized German
      cell theory. Historians have had difficulty explaining how such a 'progressive'
      biologist could have rejected cellular autonomy and the central role of the
      nucleus in cell life. The key to Huxley's thinking is provided by understanding
      his 'epigenetic' philosophy of biology.

PMID- 11823798
TI  - Stress, order and survival.
AB  - Much of the sophisticated chemistry of life is accomplished by multicomponent
      complexes, which act as molecular machines. Intrinsic to their accuracy and
      efficiency is the energy that is supplied by hydrolysis of nucleoside
      triphosphates. Conditions that deplete energy sources should therefore cause
      decay and death. But studies on organisms that are exposed to prolonged stress
      indicate that this fate could be circumvented through the formation of highly
      ordered intracellular assemblies. In these thermodynamically stable structures,
      vital components are protected by a physical sequestration that is independent of
      energy consumption.

PMID- 11823800
TI  - The Rockefeller Foundation and the rise of molecular biology.
AB  - The Rockefeller Foundation began to support a systematic transfer of physico
      chemical technology to experimental biology in the early 1930s. A close look at
      three key projects in the United Kingdom shows the impact and limits of private
      philanthropy on scientific innovation.

PMID- 11823801
TI  - Visual competition.
AB  - Binocular rivalry--the alternations in perception that occur when different
      images are presented to the two eyes--has been the subject of intensive
      investigation for more than 160 years. The psychophysical properties of binocular
      rivalry have been well described, but newer imaging and electrophysiological
      techniques have not resolved the issue of where in the brain rivalry occurs. The
      most recent evidence supports a view of rivalry as a series of processes, each of
      which is implemented by neural mechanisms at different levels of the visual
      hierarchy. Although unanswered questions remain, this view of rivalry might allow
      us to resolve some of the controversies and apparent contradictions that have
      emerged from its study.

PMID- 11823802
TI  - Hedgehog-Gli signalling and the growth of the brain.
AB  - The development of the vertebrate brain involves the creation of many cell types
      in precise locations and at precise times, followed by the formation of
      functional connections. To generate its cells in the correct numbers, the brain
      has to produce many precursors during a limited period. How this is achieved
      remains unclear, although several cytokines have been implicated in the
      proliferation of neural precursors. Understanding this process will provide
      profound insights, not only into the formation of the mammalian brain during
      ontogeny, but also into brain evolution. Here we review the role of the Sonic
      hedgehog-Gli pathway in brain development. Specifically, we discuss the role of
      this pathway in the cerebellar and cerebral cortices, and address the
      implications of these findings for morphological plasticity. We also highlight
      future directions of research that could help to clarify the mechanisms and
      consequences of Sonic hedgehog signalling in the brain.

PMID- 11823803
TI  - Development of cortical circuits: lessons from ocular dominance columns.
AB  - The development of ocular dominance columns has served as a Rosetta stone for
      understanding the mechanisms that guide the construction of cortical circuits.
      Traditionally, the emergence of ocular dominance columns was thought to be
      closely tied to the critical period, during which columnar architecture is highly
      susceptible to alterations in visual input. However, recent findings in cats,
      monkeys and ferrets indicate that columns develop far earlier, more rapidly and
      with considerably greater precision than was previously suspected. These
      observations indicate that the initial establishment of cortical functional
      architecture, and its subsequent plasticity during the critical period, are
      distinct developmental phases that might reflect distinct mechanisms.

PMID- 11823804
TI  - Anomalous perception in synaesthesia: a cognitive neuroscience perspective.
AB  - An enduring question in cognitive neuroscience is how the physical properties of
      the world are represented in the brain to yield conscious perception. In most
      people, a particular physical stimulus gives rise to a unitary, unimodal
      perceptual experience. So, light energy leads to the sensation of seeing, whereas
      sound waves produce the experience of hearing. However, for individuals with the
      rare phenomenon of synaesthesia, specific physical stimuli consistently induce
      more than one perceptual experience. For example, hearing particular sounds might
      induce vivid experiences of colour, taste or odour, as might the sight of visual
      symbols, such as letters or digits. Here we review the latest findings on
      synaesthesia, and consider its possible genetic, neural and cognitive bases. We
      also propose a neurocognitive framework for understanding such anomalous
      perceptual experiences.

PMID- 11823805
TI  - Short-term plasticity at the calyx of Held.
AB  - Synapses show widely varying degrees of short-term facilitation and depression.
      Several mechanisms have been proposed to underlie short-term plasticity, but the
      contributions of presynaptic mechanisms have been particularly difficult to study
      because of the small size of synaptic boutons in the mammalian brain. Here we
      review the functional properties of the calyx of Held, a giant nerve terminal
      that has shed new light on the general mechanisms that control short-term
      plasticity. The calyx of Held has also provided fresh insights into the
      strategies used by synapses to extend their dynamic range of operation and
      preserve the timing of sensory stimuli.

PMID- 11823806
TI  - Neurogenesis in adult primate neocortex: an evaluation of the evidence.
AB  - Reports of continuous genesis and turnover of neurons in the adult primate
      association neocortex--the site of the highest cognitive functions--have
      generated great excitement. Here, I review the available evidence, and question
      the scientific basis of this claim.

PMID- 11823808
TI  - Battling the brain drain.

PMID- 11823807
TI  - Ricardo Miledi and the calcium hypothesis of neurotransmitter release.
AB  - Ricardo Miledi has made significant contributions to our basic understanding of
      how synapses work. Here I discuss aspects of Miledi's research that helped to
      establish the requirement of presynaptic calcium for neurotransmitter release,
      from his earliest scientific studies to his classic experiments in the squid
      giant synapse.

PMID- 11823810
TI  - Summits that matter.
AB  - The European Commission has made good progress in gathering support for its new
      programme of basic and applied research. Now Europe's industries and heads of
      state need to fulfill promises made two years ago.

PMID- 11823811
TI  - Bush's budget boost puts NIH on target for doubled figures.

PMID- 11823812
TI  - Physicists head for collision course.

PMID- 11823814
TI  - Minister set to reform Australia's universities.

PMID- 11823813
TI  - Undersea plan leaves wrecks to rest in peace.

PMID- 11823815
TI  - Senators square up over cloning.

PMID- 11823816
TI  - Venter's departure sees Celera seek therapies.

PMID- 11823817
TI  - Nerve inflammation halts trial for Alzheimer's drug.

PMID- 11823818
TI  - Progress in human genetics hindered by reluctance to share.

PMID- 11823819
TI  - Survey overlap impedes fossil hunters' study.

PMID- 11823820
TI  - Delegates nudge fusion project closer to reality.

PMID- 11823823
TI  - Inspired by immunity.

PMID- 11823822
TI  - The rise of the bean counters.

PMID- 11823824
TI  - False samples are not the same as blind controls. Informal efforts to "test" a
      laboratory corrupt the data stream, where integrity is crucial.

PMID- 11823825
TI  - Mislabelling muddies the forest-survey waters.

PMID- 11823826
TI  - Regional network raises profile of local journals.

PMID- 11823827
TI  - Tax-free pay lets funders evade responsibilities.

PMID- 11823828
TI  - People, payments and positions at DESY.

PMID- 11823829
TI  - Laboratories' gravy train has ground to a halt.

PMID- 11823830
TI  - Mad hatters at the DNA tea party.

PMID- 11823837
TI  - Fact and fantasy. The zoology created by our imagination is far outstripped by
      that of reality.

PMID- 11823839
TI  - The investment forecast.

PMID- 11823838
TI  - Balance: mind-grasping gravity.

PMID- 11823841
TI  - One generation at a time.

PMID- 11823842
TI  - Function by serendipity.

PMID- 11823844
TI  - Big thinking.

PMID- 11823846
TI  - Don Craig Wiley (1944-2001).

PMID- 11823847
TI  - Massive emissions of toxic gas in the Atlantic.
AB  - Recurrent eruptions of toxic hydrogen sulphide gas in the waters along the
      Namibian coast off southwestern Africa have been considered to be local features
      with only limited ecosystem-scale consequences. But satellite remote sensing has
      revealed that these naturally occurring events are much more extensive and longer
      lasting than previously suspected, and that the resultant hypoxia may last for
      much longer. The effects on the marine ecology and valuable coastal fisheries of
      this region are likely to be important.

PMID- 11823848
TI  - Photoreceptive net in the mammalian retina. This mesh of cells may explain how
      some blind mice can still tell day from night.
AB  - We have discovered an expansive photoreceptive 'net' in the mouse inner retina,
      visualized by using an antiserum against melanopsin, a likely photopigment. This
      immunoreactivity is evident in a subset of retinal ganglion cells that
      morphologically resemble those that project to the suprachiasmatic nucleus (SCN),
      the site of the primary circadian pacemaker. Our results indicate that this
      bilayered photoreceptive net is anatomically distinct from the rod and cone
      photoreceptors of the outer retina, and suggest that it may mediate non-visual
      photoreceptive tasks such as the regulation of circadian rhythms.

PMID- 11823849
TI  - Dinosaur locomotion from a new trackway.
AB  - Ardley Quarry in Oxfordshire, UK, contains one of the most extensive dinosaur
      trackway sites in the world, with individual trackways extending for up to 180
      metres. We have discovered a unique dual-gauge trackway from a bipedal theropod
      dinosaur from the Middle Jurassic in this locality, which indicates that these
      large theropods were able to run and that they used different hindlimb postures
      for walking and running. Our findings have implications for the biomechanics and
      evolution of theropod locomotion.

PMID- 11823850
TI  - Dogfish hair cells sense hydrostatic pressure.
AB  - Many marine invertebrates and fish respond to hydrostatic pressure in order to
      regulate their depth and synchronize their behaviour to tidal cycles. Here we
      investigate the effect of hydrostatic pressure on the vestibular hair cells
      located in the labyrinth of the dogfish Scyliorhinus canicula, and find that it
      modulates their spontaneous activity and response to angular acceleration. This
      may explain not only the low resting activity of vertebrate hair cells but also
      how fish that do not have swim bladders can sense hydrostatic cues.

PMID- 11823853
TI  - Topologically protected quantum bits using Josephson junction arrays.
AB  - All physical implementations of quantum bits (or qubits, the logical elements in
      a putative quantum computer) must overcome conflicting requirements: the qubits
      should be manipulable through external signals, while remaining isolated from
      their environment. Proposals based on quantum optics emphasize optimal isolation,
      while those following the solid-state route exploit the variability and
      scalability of nanoscale fabrication techniques. Recently, various designs using
      superconducting structures have been successfully tested for quantum coherent
      operation, however, the ultimate goal of reaching coherent evolution over
      thousands of elementary operations remains a formidable task. Protecting qubits
      from decoherence by exploiting topological stability is a qualitatively new
      proposal that holds promise for long decoherence times, but its physical
      implementation has remained unclear. Here we show how strongly correlated systems
      developing an isolated twofold degenerate quantum dimer liquid ground state can
      be used in the construction of topologically stable qubits; we discuss their
      implementation using Josephson junction arrays. Although the complexity of their
      architecture challenges the technology base available today, such topological
      qubits greatly benefit from their built-in fault-tolerance.

PMID- 11823851
TI  - Lysogeny in marine Synechococcus.
AB  - Viral infection of bacteria can be lytic, causing destruction of the host cell,
      or lysogenic, in which the viral genome is instead stably maintained as a
      prophage within its host. Here we show that lysogeny occurs in natural
      populations of an autotrophic picoplankton (Synechococcus) and that there is a
      seasonal pattern to this interaction. Because lysogeny confers immunity to
      infection by related viruses, this process may account for the resistance to
      viral infection seen in common forms of autotrophic picoplankton.

PMID- 11823854
TI  - Real-space imaging of an orbital Kondo resonance on the Cr(001) surface.
AB  - The Kondo effect is usually connected with the interaction between a localized
      spin moment and itinerant electrons. This interaction leads to the formation of a
      narrow resonance at the Fermi level, which is called the Abrikosov-Suhl or Kondo
      resonance. Scanning tunnelling microscopy is an ideal technique for real-space
      investigations of complicated electronic structures and many-body phenomena, such
      as the formation of the Kondo resonance or d-wave pairing in high-T(c)
      superconductors. Theory has predicted that similar, Kondo-like many-electron
      resonances are possible for scattering centres with orbital instead of spin
      degrees of freedom--the quadruple momenta in uranium-based compounds or two-level
      systems in metallic glasses are examples of such 'pseudo-Kondo' scattering
      centres. Here we present evidence for the orbital Kondo resonance on a transition
      metal surface. Investigations of an atomically clean Cr(001) surface at low
      temperature using scanning tunnelling microscopy reveal a very narrow resonance
      at 26 meV above the Fermi level, and enable us to visualize the orbital character
      of the corresponding state. The experimental data, together with many-body
      calculations, demonstrate that the observed resonance is an orbital Kondo
      resonance formed by two degenerate d(xz), d(yz) surface states.

PMID- 11823855
TI  - Stepwise radial complexation of imine groups in phenylazomethine dendrimers.
AB  - Dendrimers are highly branched organic macromolecules with successive layers or
      'generations' of branch units surrounding a central core. Organic-inorganic
      hybrid versions have also been produced, by trapping metal ions or metal clusters
      within the voids of the dendrimers. The unusual, tree-like topology endows these
      nanometre-sized macromolecules with a gradient in branch density from the
      interior to the exterior, which can give rise to an energy gradient that directs
      the transfer of charge and energy from the dendrimer periphery to its core. Here
      we show that tin ions, Sn(2+), complex to the imine groups of a spherical
      polyphenylazomethine dendrimer in a stepwise fashion. This behaviour reflects a
      gradient in the electron density associated with the imine groups, with
      complexation in a more peripheral generation proceeding only after complexation
      in generations closer to the core has been completed. By attaching an electron
      withdrawing group to the dendrimer core, we are able to change the complexation
      pattern, so that the core imines are complexed last. By further extending this
      strategy, it should be possible to control the number and location of metal ions
      incorporated into dendrimer structures, which might find uses as tailored
      catalysts or building blocks for advanced materials.

PMID- 11823852
TI  - Genome sequence of the plant pathogen Ralstonia solanacearum.
AB  - Ralstonia solanacearum is a devastating, soil-borne plant pathogen with a global
      distribution and an unusually wide host range. It is a model system for the
      dissection of molecular determinants governing pathogenicity. We present here the
      complete genome sequence and its analysis of strain GMI1000. The 5.8-megabase
      (Mb) genome is organized into two replicons: a 3.7-Mb chromosome and a 2.1-Mb
      megaplasmid. Both replicons have a mosaic structure providing evidence for the
      acquisition of genes through horizontal gene transfer. Regions containing
      genetically mobile elements associated with the percentage of G+C bias may have
      an important function in genome evolution. The genome encodes many proteins
      potentially associated with a role in pathogenicity. In particular, many putative
      attachment factors were identified. The complete repertoire of type III secreted
      effector proteins can be studied. Over 40 candidates were identified. Comparison
      with other genomes suggests that bacterial plant pathogens and animal pathogens
      harbour distinct arrays of specialized type III-dependent effectors.

PMID- 11823856
TI  - Quantifying the risk of extreme seasonal precipitation events in a changing
      climate.
AB  - Increasing concentrations of atmospheric carbon dioxide will almost certainly
      lead to changes in global mean climate. But because--by definition--extreme
      events are rare, it is significantly more difficult to quantify the risk of
      extremes. Ensemble-based probabilistic predictions, as used in short- and medium
      term forecasts of weather and climate, are more useful than deterministic
      forecasts using a 'best guess' scenario to address this sort of problem. Here we
      present a probabilistic analysis of 19 global climate model simulations with a
      generic binary decision model. We estimate that the probability of total boreal
      winter precipitation exceeding two standard deviations above normal will increase
      by a factor of five over parts of the UK over the next 100 years. We find similar
      increases in probability for the Asian monsoon region in boreal summer, with
      implications for flooding in Bangladesh. Further practical applications of our
      techniques would be helped by the use of larger ensembles (for a more complete
      sampling of model uncertainty) and a wider range of scenarios at a resolution
      adequate to analyse average-size river basins.

PMID- 11823857
TI  - Increasing risk of great floods in a changing climate.
AB  - Radiative effects of anthropogenic changes in atmospheric composition are
      expected to cause climate changes, in particular an intensification of the global
      water cycle with a consequent increase in flood risk. But the detection of
      anthropogenically forced changes in flooding is difficult because of the
      substantial natural variability; the dependence of streamflow trends on flow
      regime further complicates the issue. Here we investigate the changes in risk of
      great floods--that is, floods with discharges exceeding 100-year levels from
      basins larger than 200,000 km(2)--using both streamflow measurements and
      numerical simulations of the anthropogenic climate change associated with
      greenhouse gases and direct radiative effects of sulphate aerosols. We find that
      the frequency of great floods increased substantially during the twentieth
      century. The recent emergence of a statistically significant positive trend in
      risk of great floods is consistent with results from the climate model, and the
      model suggests that the trend will continue.

PMID- 11823858
TI  - DNA reveals high dispersal synchronizing the population dynamics of Canada lynx.
AB  - Population dynamics of Canada lynx (Lynx canadensis) have been of interest to
      ecologists for nearly sixty years. Two competing hypotheses concerning lynx
      population dynamics and large-scale spatial synchrony are currently debated. The
      first suggests that dispersal is substantial among lynx populations, and the
      second proposes that lynx at the periphery of their range exist in small,
      isolated patches that maintain cycle synchrony via correlation with extrinsic
      environmental factors. Resolving the nature of lynx population dynamics and
      dispersal is important both to ecological theory and to the conservation of
      threatened lynx populations: the lack of knowledge about connectivity between
      populations at the southern periphery of the lynx's geographic range delayed
      their legal listing in the United States. We test these competing hypotheses
      using microsatellite DNA markers and lynx samples from 17 collection sites in the
      core and periphery of the lynx's geographic range. Here we show high gene flow
      despite separation by distances greater than 3,100 km, supporting the dispersal
      hypothesis. We therefore suggest that management actions in the contiguous United
      States should focus on maintaining connectivity with the core of the lynx's
      geographic range.

PMID- 11823859
TI  - Identification of diploid endosperm in an early angiosperm lineage.
AB  - In flowering plants, the developmental and genetic basis for the establishment of
      an embryo-nourishing tissue differs from all other lineages of seed plants. Among
      extant nonflowering seed plants (conifers, cycads, Ginkgo, Gnetales), a
      maternally derived haploid tissue (female gametophyte) is responsible for the
      acquisition of nutrients from the maternal diploid plant, and the ultimate
      provisioning of the embryo. In flowering plants, a second fertilization event,
      contemporaneous with the fusion of sperm and egg to yield a zygote, initiates a
      genetically biparental and typically triploid embryo-nourishing tissue called
      endosperm. For over a century, triploid biparental endosperm has been viewed as
      the ancestral condition in extant flowering plants. Here we report diploid
      biparental endosperm in Nuphar polysepalum, a basal angiosperm. We show that
      diploid endosperms are common among early angiosperm lineages and may represent
      the ancestral condition among flowering plants. If diploid endosperm is
      plesiomorphic, the triploid endosperms of the vast majority of flowering plants
      must have evolved from a diploid condition through the developmental modification
      of the unique fertilization process that initiates endosperm.

PMID- 11823860
TI  - Gene expression profiling predicts clinical outcome of breast cancer.
AB  - Breast cancer patients with the same stage of disease can have markedly different
      treatment responses and overall outcome. The strongest predictors for metastases
      (for example, lymph node status and histological grade) fail to classify
      accurately breast tumours according to their clinical behaviour. Chemotherapy or
      hormonal therapy reduces the risk of distant metastases by approximately one
      third; however, 70-80% of patients receiving this treatment would have survived
      without it. None of the signatures of breast cancer gene expression reported to
      date allow for patient-tailored therapy strategies. Here we used DNA microarray
      analysis on primary breast tumours of 117 young patients, and applied supervised
      classification to identify a gene expression signature strongly predictive of a
      short interval to distant metastases ('poor prognosis' signature) in patients
      without tumour cells in local lymph nodes at diagnosis (lymph node negative). In
      addition, we established a signature that identifies tumours of BRCA1 carriers.
      The poor prognosis signature consists of genes regulating cell cycle, invasion,
      metastasis and angiogenesis. This gene expression profile will outperform all
      currently used clinical parameters in predicting disease outcome. Our findings
      provide a strategy to select patients who would benefit from adjuvant therapy.

PMID- 11823861
TI  - Th1-specific cell surface protein Tim-3 regulates macrophage activation and
      severity of an autoimmune disease.
AB  - Activation of naive CD4(+) T-helper cells results in the development of at least
      two distinct effector populations, Th1 and Th2 cells. Th1 cells produce cytokines
      (interferon (IFN)-gamma, interleukin (IL)-2, tumour-necrosis factor (TNF)-alpha
      and lymphotoxin) that are commonly associated with cell-mediated immune responses
      against intracellular pathogens, delayed-type hypersensitivity reactions, and
      induction of organ-specific autoimmune diseases. Th2 cells produce cytokines (IL
      4, IL-10 and IL-13) that are crucial for control of extracellular helminthic
      infections and promote atopic and allergic diseases. Although much is known about
      the functions of these two subsets of T-helper cells, there are few known surface
      molecules that distinguish between them. We report here the identification and
      characterization of a transmembrane protein, Tim-3, which contains an
      immunoglobulin and a mucin-like domain and is expressed on differentiated Th1
      cells. In vivo administration of antibody to Tim-3 enhances the clinical and
      pathological severity of experimental autoimmune encephalomyelitis (EAE), a Th1
      dependent autoimmune disease, and increases the number and activation level of
      macrophages. Tim-3 may have an important role in the induction of autoimmune
      diseases by regulating macrophage activation and/or function.

PMID- 11823862
TI  - Phospholipase C gamma 1 is a physiological guanine nucleotide exchange factor for
      the nuclear GTPase PIKE.
AB  - Phospholipase C gamma 1 (PLC-gamma 1) hydrolyses phosphatidylinositol-4,5
      bisphosphate to the second messengers inositol-1,4,5-trisphosphate and
      diacylglycerol. PLC-gamma 1 also has mitogenic activity upon growth-factor
      dependent tyrosine phosphorylation; however, this activity is not dependent on
      the phospholipase activity of PLC-gamma 1, but requires an SH3 domain. Here, we
      demonstrate that PLC-gamma 1 acts as a guanine nucleotide exchange factor (GEF)
      for PIKE (phosphatidylinositol-3-OH kinase (PI(3)K) enhancer). PIKE is a nuclear
      GTPase that activates nuclear PI(3)K activity, and mediates the physiological
      activation by nerve growth factor (NGF) of nuclear PI(3)K activity. This
      enzymatic activity accounts for the mitogenic properties of PLC-gamma 1.

PMID- 11823863
TI  - Structural identification of a bacterial quorum-sensing signal containing boron.
AB  - Cell-cell communication in bacteria is accomplished through the exchange of
      extracellular signalling molecules called autoinducers. This process, termed
      quorum sensing, allows bacterial populations to coordinate gene expression.
      Community cooperation probably enhances the effectiveness of processes such as
      bioluminescence, virulence factor expression, antibiotic production and biofilm
      development. Unlike other autoinducers, which are specific to a particular
      species of bacteria, a recently discovered autoinducer (AI-2) is produced by a
      large number of bacterial species. AI-2 has been proposed to serve as a
      'universal' signal for inter-species communication. The chemical identity of AI-2
      has, however, proved elusive. Here we present the crystal structure of an AI-2
      sensor protein, LuxP, in a complex with autoinducer. The bound ligand is a
      furanosyl borate diester that bears no resemblance to previously characterized
      autoinducers. Our findings suggest that addition of naturally occurring borate to
      an AI-2 precursor generates active AI-2. Furthermore, they indicate a potential
      biological role for boron, an element required by a number of organisms but for
      unknown reasons.

PMID- 11823864
TI  - Mutual synergistic folding in recruitment of CBP/p300 by p160 nuclear receptor
      coactivators.
AB  - Nuclear hormone receptors are ligand-activated transcription factors that
      regulate the expression of genes that are essential for development, reproduction
      and homeostasis. The hormone response is mediated through recruitment of p160
      receptor coactivators and the general transcriptional coactivator CBP/p300, which
      function synergistically to activate transcription. These coactivators exhibit
      intrinsic histone acetyltransferase activity, function in the remodelling of
      chromatin, and facilitate the recruitment of RNA polymerase II and the basal
      transcription machinery. The activities of the p160 coactivators are dependent on
      CBP. Both coactivators are essential for proper cell-cycle control,
      differentiation and apoptosis, and are implicated in cancer and other diseases.
      To elucidate the molecular basis of assembling the multiprotein activation
      complex, we undertook a structural and thermodynamic analysis of the interaction
      domains of CBP and the activator for thyroid hormone and retinoid receptors. Here
      we show that although the isolated domains are intrinsically disordered, they
      combine with high affinity to form a cooperatively folded helical heterodimer.
      Our study uncovers a unique mechanism, called 'synergistic folding', through
      which p160 coactivators recruit CBP/p300 to allow transmission of the hormonal
      signal to the transcriptional machinery.

PMID- 11823865
TI  - Structure of the cell-puncturing device of bacteriophage T4.
AB  - Bacteriophage T4 has a very efficient mechanism for infecting cells. The key
      component of this process is the baseplate, located at the end of the phage tail,
      which regulates the interaction of the tail fibres and the DNA ejection machine.
      A complex of gene product (gp) 5 (63K) and gp27 (44K), the central part of the
      baseplate, is required to penetrate the outer cell membrane of Escherichia coli
      and to disrupt the intermembrane peptidoglycan layer, promoting subsequent entry
      of phage DNA into the host. We present here a crystal structure of the (gp5
      gp27)3 321K complex, determined to 2.9 A resolution and fitted into a cryo
      electron microscopy map at 17 A resolution of the baseplate-tail tube assembly.
      The carboxy-terminal domain of gp5 is a triple-stranded beta-helix that forms an
      equilateral triangular prism, which acts as a membrane-puncturing needle. The
      middle lysozyme domain of gp5, situated on the periphery of the prism, serves to
      digest the peptidoglycan layer. The amino-terminal, antiparallel beta-barrel
      domain of gp5 is inserted into a cylinder formed by three gp27 monomers, which
      may serve as a channel for DNA ejection.

PMID- 11823868
TI  - Perceptions of fieldwork education in Malta: Challenges and opportunities.
AB  - Academic upgrading of the occupational therapy programme in Malta has
      necessitated exploration of current fieldwork practices through a qualitative
      study. Data were collected through one-to-one interviews with 18 recently
      qualified occupational therapists. The findings showed the multi-faceted and
      complex nature of the fieldwork process, confirming the strong influence and
      relationships between the fieldwork context, the fieldwork supervisor and the
      different values and attitudes each learner brings to the fieldwork situation.
      The various practices as voiced by the participants affected the quality of their
      fieldwork experiences in different ways. Awareness of these key influences will
      pave the way forward for fieldwork education planners to provide meaningful
      experiences.

PMID- 11823867
TI  - Psychiatric occupational therapists' verbal interaction with their clients.
AB  - This study reports from a survey investigating psychiatric occupational
      therapists' (n=292) use of verbal interaction on a regular basis with their
      clients. Among predefined areas of verbal interaction, routine occupations, self
      image and ego-strengthening interventions were among the most frequently given
      alternatives. Verbal interaction with clients was more common among occupational
      therapists in outpatient care than among those in inpatient care. Verbal
      interaction with clients was also more common among occupational therapists with
      advanced education in psychodynamically oriented psychotherapy. The respondents'
      use of theoretical frames of reference was related to the focus of their verbal
      interaction with clients. Interventions to reach certain goals emerged as the
      most common category of verbal interactions. It was concluded that verbal
      interaction with clients is essential to the occupational therapy process. Future
      research needs to investigate the interplay between verbal and non-verbal
      components of interaction in occupational therapy and how patients benefit from
      these elements.

PMID- 11823869
TI  - Description of self-care training in occupational therapy: Case studies of five
      Kenyan children with cerebral palsy.
AB  - The purpose of this prospective case study design was to describe the changes in
      dressing skills for five Kenyan children with cerebral palsy who participated in
      a 10-week occupational therapy intervention programme. The training sessions were
      individually designed to meet the needs of the child. The children's performances
      on undressing and dressing and the time these tasks took was used as a baseline
      and outcome measure. These measurements were documented by video films and then
      analysed using visual inspection and converted into the scores of the Klein-Bell
      Activities of Daily Living (ADL) Scale. The results for each child were analysed
      using a simplified version of the Reliability Change Index. The results showed
      that four of the five children improved their ability to dress and that the
      children increased their time to undress significantly (p<0.05). Three children
      needed more time and two children needed less time for dressing (p<0.05). The
      results were influenced by the activity limitations among these children and the
      environmental, social backgrounds, cultural and economic situation unique to
      Kenya. It is recommended that case study research be used to validate clinical
      practice in paediatric occupational therapy and to understand cultural
      differences and its impact on health care.

PMID- 11823870
TI  - Multicontextual occupational therapy intervention: A case study of traumatic
      brain injury.
AB  - Cognitive deficits after a traumatic brain injury can result in significant
      functional limitations in all areas of daily living. An individual's ability to
      generalize learning may be limited, thus making it harder to live independently
      in the community. Assessing a client's metacognitive skills and awareness level
      may help to establish a baseline understanding about the supervision required and
      the most suitable living arrangements. This study describes a multicontextual,
      community re-entry occupational therapy programme directed at awareness training
      and compensation for cognitive problems in a 34-year-old man with traumatic brain
      injury. Intervention consisted of metacognitive training, exploration and use of
      effective processing strategies, task gradations and practice of functional
      activities in multiple environmental contexts. Strategies such as self
      prediction, self-monitoring, role reversal and the use of checklists were used.
      Results after six months of intervention show improvements in the client's
      awareness level, enhancement of his occupational function, increased satisfaction
      with performance and a decrease in the level of attendant care. Additional
      studies are recommended to validate the findings.

PMID- 11823871
TI  - Icelandic occupational therapists' attitudes towards educational issues.
AB  - The purpose of this study was to assess the readiness of occupational therapists
      in Iceland to accept a professional as opposed to a technical view of the
      profession. Most Icelandic occupational therapists were educated in other
      countries, with little emphasis on liberal arts, sciences and research. The first
      Icelandic occupational therapy programme, a university-level programme, was
      founded in 1997. All Icelandic occupational therapists were surveyed. Eighty
      seven questionnaires were sent out and 80 (92%) were returned and used for
      statistical analysis. The results of the study showed that Icelandic occupational
      therapists valued academic skills over technical skills, emphasizing occupational
      therapy theory unique to the profession and research to validate practice. More
      recognition among other health professionals was considered the most needed
      change in the profession. The results of the study showed that the clinicians'
      attitudes confirmed in general what is emphasized in the curriculum and in
      students' fieldwork. Further research is needed to explore whether the Icelandic
      occupational therapy profession succeeds in promoting research and recognition by
      other health professions.

PMID- 11823872
TI  - Fieldwork education: The future of occupational therapy depends on it.
AB  - Fieldwork continues to be the cornerstone of preparation for entry-level
      occupational therapy clinicians. During the past five years the Canadian
      healthcare system has experienced decreases in federal funding, organizational
      changes such as the movement to programme management, and increased focus on
      community-based needs. Two fieldwork projects were tested at a large health
      sciences facility, to meet the challenge of providing effective fieldwork
      experiences that build on current educational methodologies while still
      responding to changing realities in healthcare practice. The academic programme
      with which the health sciences facility is affiliated has developed a strong
      focus on self-directed learning, using problem-based and small group learning
      formats. The development, implementation and evaluation of the two fieldwork
      projects is described. Discussion focuses on the processes needed to facilitate
      innovative, flexible fieldwork models.

PMID- 11823873
TI  - Going the distance: Developing shared web-based learning programmes.
AB  - Despite a high demand for continuing professional education, it is becoming more
      challenging to provide education in a resource-limited environment that meets the
      varied needs of learners. The advent of user-friendly, interactive communication
      technology led the University of British Columbia in Canada to explore the
      feasibility of developing a web-based distance learning programme shared by
      undergraduate and practising therapists to address this problem. Potential
      benefits and challenges of distance learning, undergraduate web-learning, pilot
      test results and an assessment of therapists' interests and needs are profiled.

PMID- 11823874
TI  - Success of non-traditional students in an undergraduate occupational therapy
      programme.
AB  - An exit survey designed to examine the experiences of occupational therapy
      undergraduates was administered to 365 students in a four-year honours programme.
      The survey had a response rate of 51% (186). The survey was informed and
      supplemented by focus groups with international students and computer-mediated
      conferencing with community leaders from relevant ethnic minorities. Results
      showed that older students and those with non-traditional entry qualifications in
      this sample were as successful as school-leaver entrants (those with UK A Level
      qualifications). There were no significant differences between the support needs
      of the groups and previous experience did not have a beneficial or significant
      effect on support needs. Having to maintain part-time employment significantly
      increased the likelihood that students would consider withdrawing from the
      programme. For those who considered withdrawing but who went on to successful
      completion, the desire to practise occupational therapy following their
      successful experiences in the programme was a powerful motivator.

PMID- 11823875
TI  - SHORT REPORT Developing awareness of spirituality in occupational therapy
      students: Are our curricula up to the task?
AB  - Although spirituality is recognized as an important component of occupational
      therapy practice, students and clinicians are not well prepared to attend to this
      area. This study examines the manner and extent to which Canadian occupational
      therapy education addresses the concept of spirituality. A survey investigating
      spirituality in occupational therapy curricula was sent to all 12 Canadian
      occupational therapy programmes, with a response rate of 83%. Results indicate
      that although all Canadian occupational therapy programmes address spirituality
      in their curricula, the level of importance attached to the topic is low. Level
      of satisfaction with the preparation of students to address spirituality in
      practice is also low. A description of one Canadian occupational therapy
      programme's curriculum in the area of spirituality is included.

PMID- 11823876
TI  - SHORT REPORT Competence unfurled: Developing portfolio practice.
AB  - In this report some of the characteristics of competence are explored. Learning
      is identified as a feature of competence. If occupational therapists are to
      survive and thrive in a changing world they need to develop and use their
      learning skills effectively to maintain competence and to develop proficiency and
      expertise. Occupational therapists should take steps to document evidence of
      evolving competence in order to demonstrate professional growth over time, and
      justify continued registration with their regulatory body.

PMID- 11823877
TI  - SHORT REPORT European Network of Occupational Therapy in Higher Education: A five
      year review.
AB  - In 1995 occupational therapy programmes in Europe founded a network in Aalborg,
      Denmark, with the aim of advancing the education of occupational therapists and
      the body of knowledge of the discipline. The European Network of Occupational
      Therapy in Higher Education (ENOTHE) is one of 43 other academic networks
      supported by the European Commission. The achievements, impact and obstacles in
      the work of ENOTHE will be discussed.

PMID- 11823878
TI  - SHORT REPORT Education and research in Africa: Identifying and meeting the needs.
AB  - The development and promotion of occupational therapy in the Sub-Saharan
      continent of Africa is seen as a challenge for the World Federation of
      Occupational Therapists. It is also a challenge for pioneering occupational
      therapists, mostly ex-patriates, who have started occupational therapy services
      in many new countries of Africa over the past few years. This report identifies
      and addresses the problems. It is important that existing training centres for
      occupational therapists are maintained by attracting permanent, indigenous
      teaching staff and clinical supervisors, by promoting continuing support and
      development of existing occupational therapy services and by promoting the
      development of more rehabilitation and educational facilities. A priority is to
      help government departments to develop job structures for occupational
      therapists. Research is seen as being vital to this process. The report concludes
      by emphasizing the importance of developing confidence in the profession of
      occupational therapy by ongoing education, personal achievement and positive
      thinking.

PMID- 11823879
TI  - SHORT REPORT Technological dreams: The implications of new technologies for
      occupational therapy education and evidence-based practice.
AB  - Computer technologies will change both occupational therapy education and
      practice. Technological optimists suggest that there will be positive benefits
      for distance learning and supervision, universal equal access to information and
      expertise, and positive cross-cultural exchange. However, technologies have
      inevitable and unexpected costs. In this report I explore the potential for
      future problems with professional induction, educational reductionism, cultural
      imperialism and deprofessionalization through a review of the literature. I
      suggest that early recognition of the costs as well as the benefits of computer
      based education will be important to the development of international
      occupational therapy.

PMID- 11823880
TI  - Patients' perceptions of their participation in rehabilitation planning and
      professionals' view of their strategies to encourage it.
AB  - The purposes of this descriptive study were threefold: first, to describe how
      patients perceived their participation in the planning of their rehabilitation;
      second, to describe nurses' and occupational therapists' view of the strategies
      they used to encourage patients' participation; and third, to compare the
      perceptions of the two groups. Data was collected through semi-structured
      interviews with 57 hospitalized patients, 39 nurses and 11 occupational
      therapists. On the basis of the data patients were categorized as (a)
      'relinquishers', (b) 'participants', and (c) 'occasional participants'.
      Professionals were categorized as 'information providers' and 'rehabilitation
      practitioners'. The strategies used by the professionals to encourage patient
      participation were approximately the same irrespective of patient category. It is
      suggested that professionals need to be sensitive to the patient's desire to
      participate in the planning of a rehabilitation programme. Further research is
      recommended to investigate circumstances affecting patients' participation and
      which strategies professionals can use to encourage their participation.

PMID- 11823881
TI  - Inter-rater and test-retest reliability of the Taiwanese Rehabilitation
      Functional Scale.
AB  - The need of a standardized evaluation tool for clinical practice is acknowledged
      by occupational therapists worldwide. The purpose of this study was to examine
      the inter-rater and test-retest reliabilities of the Taiwanese Rehabilitation
      Functional Scale (TaRFS) developed in Taiwan. Seventy-five subjects with varying
      diagnoses were recruited to participate in the study. They came from an inpatient
      re-habilitation unit within a university-affiliated hospital. All participants
      were tested on a functional measure of their independence on activities of daily
      living and cognitive-social tasks, and of their sense of well-being. The Activity
      of Daily Living (ADL) and CognitiveSocial Skills (CSS) subscales of the TaRFS
      were found to be reliable across raters and times. But individual items on the
      Subjective Well Being subscale were not stable across time. The results indicated
      that the ADL subscale as well as most items in the CSS subscale of the TaRFS can
      be utilized reliably in clinical practice. The SWB subscale of the TaRFS may need
      further revision in order to be used stably across time. The development of the
      TaRFS and future revision of the scale can be beneficial for occupational
      therapists in Taiwan to provide evidence of their intervention efficacy.

PMID- 11823882
TI  - Australian occupational therapy practice in acute care settings.
AB  - Anational sample of occupational therapists was surveyed to explore the nature of
      Australian occupational therapy practice in acute care settings. Self-care was
      the major client need that therapists reported they addressed, with an initial
      interview being the most common assessment procedure. Client education was the
      most frequently used intervention. The most important skills therapists reported
      for effective practice in acute care were time management, quick clinical
      reasoning and lateral thinking. Important workplace characteristics included a
      cooperative healthcare team and early referral. Therapists reported that their
      most important resources were supportive senior therapists and a well-resourced
      equipment pool. Three attitudinal factors emerged. Therapists in
      interdisciplinary teams and those with more experience had more positive
      attitudes. Younger therapists experienced more concern about not being able to do
      more for their patients. Results suggest a need for graduates to be better
      prepared in some skill areas and to have more realistic expectations of practice
      in this area. Department managers need to ensure younger therapists receive
      adequate support from senior therapists. Further research is needed to determine
      how best to provide this support and to further examine the influence of the
      education experience on practice expectations.

PMID- 11823884
TI  - How does work work for people with bipolar affective disorder? 
AB  - Despite modern treatments, bipolar disorder remains a chronic, relapsing disorder
      that leads to long-term psychosocial disability. A review of the literature
      suggests that while employment rates amongst individuals with bipolar disorder
      may improve over time, and are relatively better compared to some other chronic
      mental disorders, employment prospects do not match the high scholastic
      achievements seen amongst this group of people before the onset of their illness.
      For those with bipolar disorder, clinical recovery does not necessarily mean
      functional recovery, and the usual early age of onset may further reduce an
      individual's preparedness for employment. Two brief vignettes are used to discuss
      how occupational therapists can help their clients maintain their sense of hope
      in vocational recovery, gain better self-awareness and work with clients at
      various stages of recovery rather than waiting for full functional recovery.
      Further research is required to help identify specific factors that contribute to
      the success of employment integration amongst people with bipolar disorder.

PMID- 11823883
TI  - Inquiry-based learning: An instructional alternative for occupational therapy
      education.
AB  - An inquiry-based learning (IBL) approach was used as the model of instruction in
      one of three sections offered annually to large introductory occupational therapy
      classes in a Canadian university during 1994/5, 1995/6, 1996/7. Students' final
      grades in this pre-entry course form part of the grade point average on which
      admission to the BSc OT programme is based. The IBL model was employed to (1)
      increase the amount of student-directed learning, (2) increase the amount of
      independent problem-solving, (3) increase student-instructor interaction within
      the learning situation, and (4) reduce the number of in-class hours for students.
      This study is an evaluation of whether students from the IBL sections would
      subsequently do as well as those from other sections in selected junior
      professional courses. Students from the three IBL sections (n=47) were peer
      matched to students who had completed other sections of the introductory course,
      but were part of the same admission cohort (n=68). Their grades in three junior
      professional courses were compared at the end of their first year in the BSc OT
      programme. Results indicated that students from the IBL sections did at least as
      well as those from other sections where a different instructional approach was
      used, and those from the IBL sections in 1994/5 and 1996/7 each did significantly
      better on two of the junior professional courses used as the outcome measure:
      therapeutic occupation and assessment and evaluation techniques. Students
      reported that the IBL experience stimulated them to learn more about the field,
      helped them develop problem-solving skills in relation to occupational therapy,
      and enabled them to learn more about career opportunities in occupational
      therapy. Mature students were more positive about the IBL approach than students
      in their first year of university.

PMID- 11823885
TI  - Work-related stress and occupational therapy.
AB  - Occupational stress and burnout have been studied extensively in the human
      services. It has been suggested that healthcare professionals in particular are
      at risk of stress owing to the caring nature of their work. Articles related to
      occupational therapy and work-related stress were reviewed in regard to practice
      in Australia, Canada, the United Kingdom, the United States and Sweden. Although
      the empirical literature is relatively weak for occupational therapy, it has been
      argued that occupational therapists in health care share risk factors with other
      healthcare professionals. These risk factors include repeated exposure to
      distress and difficult behaviour, prolonged interventions and uncertain outcome.
      Issues such as professional status, staffing issues and the nature of the
      profession have been identified as additional risk factors for occupational
      therapists. However, empirical studies that enable burnout rates of occupational
      therapists to be compared with those of related occupational groups suggest that
      this may not be the case. Occupational therapists may in fact be protected from
      some stress and burnout factors. Further research is recommended to clarify the
      nature of stress experienced by occupational therapists and to identify both risk
      and protective factors characteristic of the profession.

PMID- 11823886
TI  - 5-HT3 receptor antagonist MDL 72222 attenuates cocaine- and mazindol-, but not
      methylphenidate-induced neurochemical and behavioral effects in the rat.
AB  - RATIONALE: It has previously been demonstrated that the 5-HT(3) receptors located
      in the mesolimbic brain areas are able to modulate the dopaminergic effects of
      various abused drugs, including cocaine (COC). OBJECTIVES: The present
      experiments investigated the role of 5-HT(3) receptors in the actions of selected
      monoamine uptake inhibitors. METHODS: The ability of the 5-HT(3) receptor
      antagonist MDL 72222 (MDL; 0.1 and 1.0 mg/kg) to modify the neurochemical and
      behavioral changes induced by COC (20 mg/kg), mazindol (MAZ; 10 mg/kg), and
      methylphenidate (MP; 5.0 or 10, and 20 mg/kg) was assessed with an in vivo
      microdialysis technique, a conditioned place preference method, and motor
      activity measurements. RESULTS: MDL robustly attenuated the elevation of
      extracellular dopamine levels in the nucleus accumbens, acquisition of place
      preference, and motor activity induced by COC and MAZ, but not those induced by
      MP, the only drug with no significant effect on 5-HT. In contrast, expression of
      COC-induced place preference was not attenuated by MDL. CONCLUSIONS: These
      results show that COC- and MAZ-induced reward-related neurochemical and
      behavioral effects, preferentially those implicated in development of conditioned
      reward, are modified by the 5-HT(3) blockade. In contrast to COC and MAZ, the
      changes induced by MP, which has less effect on the serotonergic system, remain
      unchanged. Thus it appears that involvement of a serotonergic component in the
      mechanism of action of a drug could be a prerequisite for effective antagonism by
      5-HT(3) receptor blockers.

PMID- 11823888
TI  - Neuronal nitric oxide synthase inhibition decreases cocaine self-administration
      behavior in rats.
AB  - RATIONALE: Inhibitors of nitric oxide synthase (NOS) have been shown to alter
      behaviors related to cocaine addiction, including its self-administration.
      However, previous studies have largely used mixed-action NOS inhibitors and have
      not examined the effects of a neuronal NOS inhibitor on cocaine self
      administration. OBJECTIVES: Pretreatment with the neuronal NOS inhibitor 7
      nitroindazole (7-NI) was used and its effects on cocaine self-administration were
      compared with those produced by pretreatment with an indirect dopamine receptor
      agonist (cocaine) and a D(1)-like dopamine receptor antagonist (SCH 23390).
      METHODS: Rats were trained to self-administer 1 mg/kg cocaine under a second
      order schedule of drug delivery, which measures drug-seeking behavior
      independently from drug intake. Pretreatment with various doses of 7-NI, cocaine,
      and SCH 23390 were tested in combination with the training dose of cocaine
      followed by studies examining the effects of a selected dose of each pretreatment
      drug in combination with a range of cocaine doses. Other rats were trained under
      a second-order schedule of food pellet delivery and pretreated with 7-NI,
      cocaine, or SCH 23390 to determine the behavioral specificity of the effects of
      these drugs for cocaine-maintained responding. RESULTS: The results demonstrated
      that 7-NI reduced responses maintained by the cocaine training dose and produced
      a downward shift in the cocaine dose-response curve. Changes in drug intake were
      minor by comparison. Cocaine pretreatment produced effects similar to 7-NI, while
      the changes observed after SCH 23390 pretreatment were different from 7-NI and
      cocaine. The reductions in cocaine-maintained responding after 7-NI pretreatment
      were behaviorally specific because there was no effect of 7-NI on food-maintained
      responding within the dose range examined. CONCLUSIONS: By selectively reducing
      drug-seeking behavior, these data suggest that 7-NI may enhance the reinforcing
      effects of cocaine.

PMID- 11823887
TI  - Depot naltrexone: long-lasting antagonism of the effects of heroin in humans.
AB  - RATIONALE: Naltrexone, an opioid antagonist, is currently approved as a treatment
      for heroin dependence. However, naltrexone is generally not well accepted by
      patients, and medication non-compliance is a difficult obstacle to treatment. A
      sustained-release form of naltrexone may improve compliance. OBJECTIVE: The
      present study was designed to evaluate the time course, safety, and effectiveness
      of a depot formulation of naltrexone (Depotrex). METHODS: Twelve heroin-dependent
      individuals participated in an 8-week inpatient study. After a 1-week
      detoxification period, six participants received 192 mg naltrexone base and six
      participants received 384 mg naltrexone base. For safety, the low dose of depot
      naltrexone was tested before the high dose. The effects of heroin (0, 6.25, 12.5,
      18.75, 25 mg, i.v.) were evaluated for the next 6 weeks. One dose of heroin was
      tested per day on Mondays through Fridays, and the entire dose range was tested
      each week. Active heroin doses were administered in ascending order during the
      week, while placebo could be administered on any day. Subjective, performance,
      and physiological effects were measured both before and after heroin
      administration. The hypotheses were that depot naltrexone would antagonize the
      effects of heroin, and that the high dose of depot naltrexone would produce a
      more effective and longer-lasting antagonism than the low dose. RESULTS: The low
      and high doses of depot naltrexone antagonized heroin-induced subjective ratings
      for 3 and 5 weeks, respectively. Plasma levels of naltrexone remained above 1
      ng/ml for approximately 3 and 4 weeks after administration of 192 mg and 384 mg
      naltrexone. Other than the initial discomfort associated with the injection of
      depot naltrexone, there were no untoward side-effects. CONCLUSIONS: These results
      suggest that this depot formulation of naltrexone provides a safe, effective,
      long-lasting antagonism of the effects of heroin.

PMID- 11823889
TI  - Hyperactivity and dopamine D1 receptor activation in mice lacking girk2 channels.
AB  - RATIONALE: G-protein-coupled inwardly rectifying potassium channels (GIRKs)
      regulate synaptic transmission and neuronal firing rates. Co-localization of
      GIRK2 channels and dopamine receptors in the mesolimbic system suggests a role in
      regulation of motor activity. OBJECTIVES: To explore the role of GIRK channels in
      the regulation of motor behavior. METHODS: GIRK2 null mutant mice (knockout) were
      used. Locomotor activity in a mildly stressful situation was conducted either in
      a circular open field with video tracking or in standard mouse cages equipped
      with infrared sensors. Drugs were injected intraperitoneally or subcutaneously.
      RESULTS: GIRK2 knockout mice demonstrated a transient "hyperactive" behavioral
      phenotype with initially higher motor activity and slower habituation in a novel
      situation, increased levels of spontaneous locomotor activity during dark phase
      in their home cages, and impaired habituation in the open-field test. After
      habituation, GIRK2 knockout mice showed higher motor activity, which was
      inhibited by the D(1) receptor antagonist SCH 23390 and was more sensitive to the
      activating effects of the D(1) receptor partial agonist SKF 38393. In a novel
      environment (open-field) only the highest dose of SKF 38393 used (20 mg/kg)
      produced significant activation, perhaps due to a ceiling effect in GIRK2
      knockout mice. SCH 23390 inhibited the basal activity levels of mice of both
      genotypes. CONCLUSIONS: Activation of the dopamine D(1)receptor in a stressful
      environment may be stronger in GIRK2 deficient mice, and this modified function
      of D(1) receptors may cause the transient hyperactive behavioral phenotype of
      these mice.

PMID- 11823890
TI  - Involvement of CB1 cannabinoid receptors in emotional behaviour.
AB  - RATIONALE: Endogenous and exogenous cannabinoids acting through the CB1
      cannabinoid receptors are implicated in the control of a variety of behavioural
      and neuroendocrine functions, including emotional responses, and learning and
      memory processes. Recently, knockout mice deficient in the CB1 cannabinoid
      receptor have been generated, and these animals result in an excellent tool to
      evaluate the neurophysiology of the endogenous cannabinoid system. OBJECTIVES: To
      establish the role of the CB1 cannabinoid receptor in several emotional-related
      behavioural responses, including aggressiveness, anxiety, depression and learning
      models, using CB1 knockout mice. METHODS: We evaluated the spontaneous responses
      of CB1 knockout mice and wild-type controls under different behavioural
      paradigms, including the light/dark box, the chronic unpredictable mild stress,
      the resident-intruder test and the active avoidance paradigm. RESULTS: Our
      findings showed that CB1 knockout mice presented an increase in the aggressive
      response measured in the resident-intruder test and an anxiogenic-like response
      in the light/dark box. Furthermore, a higher sensitivity to exhibit depressive
      like responses in the chronic unpredictable mild stress procedure was observed in
      CB1 knockout mice, suggesting an increased susceptibility to develop an anhedonic
      state in these animals. Finally, CB1 knockout mice showed a significant increase
      in the conditioned responses produced in the active avoidance model, suggesting
      an improvement of learning and memory processes. CONCLUSIONS: Taken together
      these findings demonstrate that endogenous cannabinoids through the activation of
      CB1 receptors are implicated in the control of emotional behaviour and
      participate in the physiological processes of learning and memory.

PMID- 11823891
TI  - Effects of fenfluramine, m-CPP and triazolam on repeated-acquisition in squirrel
      monkeys before and after neurotoxic MDMA administration.
AB  - RATIONALE: Establishing functional deficits as a result of neurotoxic dosing
      regimens of MDMA has been difficult. However, moderate success has been achieved
      when sensitive animal models and drug challenge have been used together.
      OBJECTIVE: The present study used a repeated-acquisition technique and dose
      effect determinations before, during and after neurotoxic MDMA exposure to
      characterize the effects of serotonergic drugs on learning, and to determine if
      MDMA-induced serotonin (5-HT) neurotoxicity is associated with learning deficits
      as measured by changes in response rate or the percentage of errors. METHOD: The
      effects of various serotonergic drugs were characterized in six squirrel monkeys
      responding under a repeated-acquisition procedure before and after neurotoxic
      dose regimens of MDMA. Specifically, cumulative dose-effect curves for m-CPP
      (0.032-1 mg/kg), fenfluramine (0.1-3.2 mg/kg) and triazolam (0.0032-0.1 mg/kg)
      were obtained prior to MDMA administration, with the latter drug serving as a non
      5-HT control. RESULTS: In general, all of the drugs tested decreased overall
      response rate as the cumulative dose increased, whereas only triazolam markedly
      increased the percentage of errors. MDMA treatment produced significant (80-99%)
      decreases in brain 5-HT and 5-HIAA axonal markers, but did not lead to changes in
      either dependent measure of responding or shifts in the dose-effect curves
      obtained during pharmacological challenges with m-CPP, fenfluramine or triazolam.
      CONCLUSIONS: Taken together, these results demonstrate that serotonergic drugs
      can disrupt learning in monkeys, but indicate that MDMA-induced 5-HT
      neurotoxicity does not lead to disruptions in this particular type of serial
      learning task.

PMID- 11823892
TI  - The effects of smoked cocaine during the follicular and luteal phases of the
      menstrual cycle in women.
AB  - RATIONALE: Few studies have systematically determined whether the response to
      cocaine in human females is related to hormonal fluctuations at different phases
      of the menstrual cycle. OBJECTIVES: To investigate the responses to repeated
      doses of smoked cocaine in women during two phases of the menstrual cycle using a
      within-subject design. METHODS: Eleven non-treatment seeking female cocaine
      smokers were administered smoked cocaine during the follicular and mid-luteal
      phases of the menstrual cycle. The order of menstrual cycle phase was
      counterbalanced across women and the order of cocaine doses was randomized.
      During each phase, there were four cocaine administration sessions. During each
      session, participants could smoke up to six doses of cocaine (either 0, 6, 12, or
      25 mg cocaine base, depending on the session) at 14-min intervals. RESULTS: The
      number of cocaine doses administered did not vary between the follicular and
      luteal phases. After cocaine administration, heart rate and several ratings -
      such as "good drug effect", "high", "stimulated", and "drug quality ratings" -
      were increased more during the follicular phase than the luteal phase, although,
      for some measures, these effects varied based on the cocaine dose. Further,
      dysphoric mood during the luteal phase was improved after cocaine administration.
      CONCLUSIONS: These results indicate that the cardiovascular and subjective
      effects of repeated doses of smoked cocaine are complex and vary as a function of
      menstrual cycle phase and cocaine dose.

PMID- 11823893
TI  - Role of D1-like receptors in amphetamine-induced behavioral sensitization: a
      study using D1A receptor knockout mice.
AB  - RATIONALE: The role played by D(1)-like receptors in amphetamine-induced
      behavioral sensitization has been examined using both the D(1)-like receptor
      antagonist, SCH 23390, and the D(1A) receptor knockout mouse (i.e. D(1A)
      deficient mice). Studies using these two approaches have provided conflicting
      evidence about the importance of D(1)-like receptors for amphetamine-induced
      behavioral sensitization. OBJECTIVE: The purpose of the present study was to
      determine: (a) whether D(1A)-deficient mice exhibit amphetamine-induced locomotor
      sensitization after 3 and 17 drug abstinence days, and (b) whether SCH 23390,
      which binds to both D(1A) and D(1B) receptor subtypes, blocks development of
      amphetamine sensitization in wild-type and D(1A)-deficient mice. METHODS: In the
      first experiment, adult wild-type and D(1A)-deficient mice were injected with
      amphetamine (0, 1, 2, 4, or 8 mg/kg, IP) for 7 consecutive days. In the second
      experiment, wild-type and D(1A)-deficient mice were pretreated with SCH 23390 (0,
      0.15, or 0.5 mg/kg, IP) 30 min prior to being injected with amphetamine (0 or 8
      mg/kg, IP). After each daily amphetamine injection, mice were placed in activity
      chambers where distance traveled (i.e. horizontal locomotor activity) was
      measured for 60 min. On the test days, which occurred after 3 or 17 drug
      abstinence days, mice were injected with 1 mg/kg amphetamine and locomotion was
      measured for 120 min. RESULTS: Both wild-type and D(1A)-deficient mice exhibited
      amphetamine-induced locomotor sensitization. Pretreatment with 0.5 mg/kg SCH
      23390 blocked the development of locomotor sensitization in wild-type mice, but
      did not alter the sensitized responding of D(1A)-deficient mice. CONCLUSIONS: It
      appears that D(1)-like receptors are necessary for the development of amphetamine
      sensitization in wild-type mice, while neither the D(1A) nor D(1B) receptor
      subtypes are necessary for the amphetamine-induced locomotor sensitization of
      D(1A)-deficient mice. A possible explanation for these conflicting results is
      that D(1A)-deficient mice may have a compensatory mechanism (not involving D(1B)
      receptors) that allows them to exhibit amphetamine-induced behavioral
      sensitization in the absence of the D(1A) receptor.

PMID- 11823894
TI  - Intake of saccharin, salt, and ethanol solutions is increased by infusion of a mu
      opioid agonist into the nucleus accumbens.
AB  - RATIONALE: Endogenous opioids have been implicated in the hedonic evaluation of
      food and palatability. Opioids may also be involved in alcohol intake, as there
      is a positive correlation between alcohol drinking and preference for sweets and
      fats. Our previous studies have shown that mu opioid stimulation of the nucleus
      accumbens preferentially augments intake of palatable food containing sucrose and
      fat. OBJECTIVE: The first goal of the present study was to further explore the
      nature of the involvement of mu opioids within the nucleus accumbens in ingestive
      behavior by investigating the importance of orosensory reward in opioid-mediated
      feeding, using non-caloric tasty substances (saccharin and salt). Second, we
      investigated whether mu opioid receptors within the nucleus accumbens also
      regulate alcohol consumption. METHODS: The mu agonist, D-Ala2, NMe-Phe4, Glyol5
      enkephalin (DAMGO; 0, 0.025 and 0.25 microg/0.5 microl per side), was
      microinfused into the nucleus accumbens, and intake of 0.6% saline, 0.15% sodium
      saccharin, water, and 6% ethanol was measured. RESULTS: Microinfusion of DAMGO
      into the nucleus accumbens increased the drinking of salt and saccharin solutions
      in non-deprived rats. However, water intake was not increased by this treatment
      in water-deprived rats. Mu opioid stimulation of the nucleus accumbens also
      augmented ethanol intake in rats not deprived of fluid, while leaving water
      intake unchanged when water was concurrently available. CONCLUSION: These results
      provide evidence to suggest that the mu opioid system within the ventral striatum
      regulates ingestive behavior via a mechanism related to the hedonic assessment of
      taste. In addition, the nucleus accumbens may be a key brain area where ethanol
      interacts with endogenous opioid systems, and thus may be a common neural
      substrate for both food palatability and alcohol drinking.

PMID- 11823895
TI  - Brain, plasma and tissue pharmacokinetics of risperidone and 9-hydroxyrisperidone
      after separate oral administration to rats.
AB  - RATIONALE: Following an oral dose of risperidone (RSP), concentrations of its
      major metabolite 9-hydroxyrisperidone (9-OHRSP) were high in plasma and tissues
      but disproportionately lower in the brain compared to RSP, indicating that 9
      OHRSP may have different pharmacokinetic properties. OBJECTIVES: To investigate
      non-compartmental pharmacokinetics of RSP and 9-OHRSP in plasma, brain and other
      tissues after separate administration of a single oral dose of 6 mg/kg RSP and 9
      OHRSP to rats. METHODS: Plasma, brain, liver, lung, kidney and spleen tissues
      were collected at pre-dose and at 0.5, 1, 2, 5, 6, 12, 24, 36 and 48 h post-dose,
      homogenized in saline and assayed for RSP and 9-OHRSP using a sensitive and
      specific liquid chromatography tandem mass spectrometry method. RESULTS: The
      concentration-time curve of RSP and 9-OHRSP showed that they were readily
      absorbed and followed a multiphase elimination pattern. The terminal elimination
      half-life (t(1/2) ) of RSP after the RSP dose was longest in the liver (17.6 h)
      and shortest in the spleen (1.2 h). The t(1/2)of 9-OHRSP after the RSP dose was
      shorter in plasma (3.4 h) and other tissues (approximately 8-11 h) than that for
      RSP but it was longer in the spleen. However, the t(1/2) of 9-OHRSP after the 9
      OHRSP dose was shorter in most tissues as compared to the t(1/2) of 9-OHRSP after
      the RSP dose. The area under the concentration-time curve (AUC) of RSP and 9
      OHRSP was 6-67 times higher in the plasma and tissues than in the brain. AUCs of
      9-OHRSP in tissues after the RSP dose were 2-5 times higher than those for RSP,
      except in the brain, where AUCs of RSP and 9-OHRSP were similar. CONCLUSION:
      Pharmacokinetics of 9-OHRSP in many tissues were different after RSP and 9-OHRSP
      doses. The reason for disproportionate brain levels of 9-OHRSP is not clear. The
      overall exposure to active drug in the brain as represented by AUC was similar
      after the RSP and 9-OHRSP doses and the 9-OHRSP is probably an equal contributor
      to the pharmacological actions of RSP.

PMID- 11823896
TI  - Chromium treatment decreases the sensitivity of 5-HT2A receptors.
AB  - RATIONALE: Recent case series suggest that chromium picolinate in doses of 400
      microg daily may have antidepressant properties, perhaps through increasing the
      peripheral availability of tryptophan for brain serotonin (5-HT) synthesis.
      OBJECTIVES: To determine the effects of chromium treatment on plasma tryptophan
      availability and on brain 5-HT function in human and animal models. METHODS: We
      studied the effects of short-term chromium supplementation on plasma
      concentrations of tryptophan and other large neutral amino acids. Brain 5-HT
      function was assessed by measuring the corticosterone/cortisol response to the 5
      HT precursor, 5-hydroxytryptophan (5-HTP), a response believed to be mediated via
      indirect activation of 5-HT(2A) receptors. RESULTS: In rats, chromium increased
      peripheral and central tryptophan availability and elevated brain 5-HT content.
      Changes in peripheral tryptophan availability were not seen in humans but in both
      rats and humans, chromium lowered the cortisol response to challenge with 5-HTP.
      CONCLUSIONS: Chromium can modify brain 5-HT function in humans and animals,
      perhaps by altering the sensitivity of central 5-HT(2A) receptors.

PMID- 11823898
TI  - Managing reboxetine-associated urinary hesitancy in a patient with major
      depressive disorder: a case study.

PMID- 11823897
TI  - Long-term changes in social interaction and reward following repeated MDMA
      administration to adolescent rats without accompanying serotonergic
      neurotoxicity.
AB  - RATIONALE: MDMA is a popular drug of abuse in adolescents which causes
      serotonergic neurotoxicity in adult but not young rodents. However, few studies
      have examined the long-term behavioural consequence of MDMA and it is unclear
      whether such changes occur in the absence of neurotoxicity. OBJECTIVES: The
      present study examined whether treatment of young rats with MDMA produced long
      term behavioural alterations without accompanying serotonergic neurotoxicity.
      METHOD: Male Lister hooded rats ( n=36, postnatal day (PND) 39) received MDMA
      (7.5 mg/kg i.p., twice daily for 3 days) or saline (l ml/kg i.p.) and the acute
      effect on open field behaviour and body temperature was monitored. Following drug
      withdrawal, social interaction in pre-treatment- and weight-matched rat pairs,
      cortical [(3)H]paroxetine binding and hippocampal and frontal cortical serotonin
      and dopamine levels (PND 53, n=12) and conditioned place preference (PND 70,
      n=24) to cocaine (5 mg/kg IP) were analysed. RESULTS: MDMA elicited the expected
      immediate serotonin syndrome with significant hyperlocomotion, decreased rearing
      and hypothermia. Twelve to 29 days after the last MDMA injection social
      interaction was significantly attenuated (by 41%) and the sub-threshold
      conditioned place preference to cocaine was significantly enhanced compared with
      that in saline controls, although no significant side preference to cocaine
      occurred in the latter. MDMA pre-treatment did not alter 5-HT levels or cortical
      [(3)H]paroxetine binding. CONCLUSION: MDMA administration to adolescent rats
      reduced social interaction and enhanced the sub-threshold rewarding effect of
      cocaine at adulthood, despite an absence of accompanying serotonergic and
      dopaminergic neurotoxicity.

PMID- 11823921
TI  - [Fundamentals of functional magnetic resonance imaging in clinical psychology and
      psychiatry].
AB  - In the last few years, functional magnetic resonance imaging (fMRI) has become
      the preferred technique for brain mapping because of its superior spatial and
      temporal resolution. Other factors that have contributed to the popularity of
      this imaging method are the increasing availability of scanners and the
      technological advances made in data acquisition and analysis. This paper
      describes basic principles of fMRI essential to a comprehension of the
      capabilities of this complex technology. In particular, it focuses on blood
      oxygenation level dependent (BOLD) contrast, on the experimental procedures, as
      well as on possible imaging techniques and statistical analyses. Examples for
      studying brain-behavior-relationships come from research in the context of
      emotion in healthy subjects as well as in emotional dysfunctions in psychiatric
      patients.

PMID- 11823922
TI  - [Financial burden on spouses of patients suffering from schizophrenia, depression
      or anxiety disorder].
AB  - The aim of this study was to compare financial burden of spouses, whose relative
      suffers from schizophrenia, depression or anxiety disorder. 151 spouses filled in
      the questionnaire about illness related expenses and financial loss. Additionally
      they estimate their subjective burden according to these experienced costs.
      Direct cash expenditures on behalf of the patients' illness were reported by 66 %
      spouses. In the sampling the amount of spent money did not differ statistically,
      however spouses of patients with anxiety disorder emphasised experiencing
      financial strain and described more often subjective economic disadvantages.
      Although most spouses of patients with psychiatric disorders experience illness
      related financial disadvantages, these costs were usually not considered as
      serious problem or as burdensome. Based on a subjective hierarchy of burdens
      financial problems can be regarded as less important for spouses of patients with
      mental illness. Thus, not only the material, but also the immaterial costs of
      care giving spouses should be taken into consideration when planning health
      policy decisions.

PMID- 11823923
TI  - [Influence of treatment with acetyl-cholinesterase inhibitors on
      psychopathological symptoms in Alzheimer's disease].
AB  - The treatment of the cognitive deficits has been the major focus in patients with
      Alzheimer's disease (DAT) so far. Recently there is increasing interest in
      Behavioral and Psychological Symptoms of Dementia (BPSD), which can place much
      burden on DAT patients and their caregivers. With the introduction of
      Acetylcholinesterase Inhibitors (AChEI) of the second generation the therapeutic
      armament has been extended. The clinical evaluation of AChEI has found growing
      evidence that these compounds do not only improve cognitive abilities and
      activities of daily living (ADL), but also BPSD. The given data regarding the
      three AChEI available on the market allow the conclusion that there is a general
      improvement in BPSD. Beside these particularly positive effects on
      hallucinations, mood symptoms, aggressiveness, and agitation seem possible but
      need further clarification.

PMID- 11823924
TI  - [Psychiatric examination of accused for the "United Nations International
      Tribunal for the prosecution of persons responsible for serious violations of
      International Humanitarian Law committed in the territory of the former
      Yugoslavia" (ICTY)].
AB  - Psychiatric examination of accused for the International Tribunal is a new and
      challenging task for expert medical witness and forensic psychiatry. After a
      brief description of a case report relevant aspects of psychiatric evaluation of
      persons responsible for war crimes are outlined and possible implications for
      forensic research are discussed.

PMID- 11823925
TI  - [Mechanism-based treatment principles of neuropathic pain].
AB  - Traditionally, neuropathic pain has been classified due to aetiology of nerve
      damage-traumatic, inflammatory or metabolic, for instance. Based on this
      classification, pain therapy often is insufficient. Recent research revealed
      different mechanisms, which are responsible for the generation of pain after
      nerve lesion. These mechanisms seem to be independent of aetiology of the nerve
      damage. The most important mechanisms are accumulation of sodium channels on
      injured nerves, pathological sympatho-afferent coupling, disinhibition of
      nociception and central or peripheral nociceptive sensitisation. Each individual
      mechanism could be treated specifically by current available drugs, or by non
      drug therapy. However, future research has to focus on exploring tools to
      recognise individual pain mechanisms in single patients. Thereby treatment will
      become more effective.

PMID- 11823926
TI  - [Syncope - a systematic overview of classification, pathogenesis, diagnosis and
      management].
AB  - Syncope is defined as a temporary interruption of cerebral perfusion with a
      sudden and transient loss of consciousness and spontaneous recovery.
      Approximately one third of the population experiences syncope at least once
      during a lifetime. Presyncopal signs and symptoms, including weakness, headache,
      blurred vision, diaphoresis, nausea, and vomiting are sometimes present for
      seconds or minutes prior to loss of consciousness. After syncope, the patients
      may present with persisting drowsiness, headache, dizziness, nausea, but not
      usually confusion. Causes of syncope have been categorized as cardiovascular, non
      cardiovascular, and unexplained. Cardiovascular causes can be subdivided into
      structural heart disease, coronary heart disease, and arrhythmia. Non
      cardiovascular causes include neurological, metabolic, psychiatric and other
      disorders.Orthostatic hypotension - one of the most frequent causes of syncope -
      has manifold etiologies comprising various neurological and internal diseases.
      Orthostatic hypotension usually can be attributed to an impairment of peripheral
      vasoconstriction or to a reduction of the intravascular volume. Signs and
      symptoms, including the above prodromi are often present just after rising from a
      supine or sitting position. Frequently, blood pressure decreases significantly
      without an increase in heart rate. Autonomic cardiovascular modulation is often
      reduced. Many of the patients with "unexplained" syncope experience neurally
      mediated (i. e. neurocardiogenic or vasovagal) syncope. In these patients,
      cardiovascular control may be stable for an extended period of time during
      orthostatic stress, then there is a sudden decrease in blood pressure and heart
      rate. Neurocardiogenic or neurally mediated syncope can be associated with
      painful or emotionally stressful situations such as anxiety or fear, with
      prolonged standing or specific trigger situations such as micturition,
      defecation, coughing or sneezing, visceral or carotid sinus stimulation, or with
      trigeminal or glossopharyngeal neuralgia. So far, the mechanisms of
      neurocardiogenic syncope are not completely understood. The passive 60 degrees to
      70 degrees head-up tilt test is useful for the diagnosis of orthostatic and
      neurally mediated syncope. The sensitivity of the test can be improved by
      additional pharmacological provocation, e. g. by isoproterenol, or by increased
      orthostatic stress using lower body negative pressure stimulation. For the
      treatment of syncope one should first consider non-pharmacological options.
      Patients with orthostatic hypotension should avoid rapid changes of the body
      position from supine to standing, as well as high room temperature or other
      situations inducing peripheral vasodilatation. An increased intake of sodium and
      fluids, mild physical exercise or so-called postural counter-maneuvers can
      improve orthostatic tolerance. Among the drugs recommended for pharmacologic
      treatment are mineralocorticoids (e. g. fludrocortisone), vasoconstrictor agents
      (e. g. ephedrine, midodrine), adenosine receptor blockers (theophylline) and
      beta2-blockers (propanolol), anticholinergic agents, e. g. scopolamine or
      disopyramide, and negative cardiac inotropes, e. g. beta1-adrenergic blockers or
      disopyramide. Serotonin reuptake inhibitors (e. g. fluoxetine, sertraline),
      alpha2-adrenergic agonists (clonidine), central nervous system stimulants such as
      methylphenidate or phentermine are thought to be beneficial in specific cases.
      Cardiac pacemakers often seem to be recommended without adequate indication. The
      antidiuretic, V2-receptor specific, vasopressin analogue desmopressin increases
      the intravascular volume. Erythropoietin improves anemia and red blood cell
      decrease and augments blood pressure and cerebral oxygenation. In postprandial
      hypotension, octreotide, a somatostatin analogue, prostaglandin inhibitors such
      as indomethacin or ibuprofen, as well as metoclopramide or two cups of coffee per
      day might be beneficial.

PMID- 11823928
TI  - Tissue matrices for soft tissue and mucosal augmentation and replacement.
AB  - Facial plastic surgery frequently involves the replacement or augmentation of
      facial soft tissue and mucosal surfaces. Material and technique advancements in
      this area are frequent. Surgeons must remain knowledgeable to provide patients
      with services that best meet individual needs. We review the concepts that guide
      this decision process and discuss a variety of materials: old, new, and
      investigational. A greater understanding of the options available, with their
      inherent risks and benefits, increases the surgeon's ability to communicate and
      guide patients in their decision-making process. New materials will continue to
      be developed and play a role as the search for the optimal replacement of soft
      tissue and mucosa continues.

PMID- 11823929
TI  - Bone healing and bone substitutes.
AB  - With the advent of new biomaterials and surgical techniques, the reconstructive
      surgeon has a wider range of treatment modalities for the rehabilitation and
      reconstruction of craniofacial skeletal deformities than ever before. These
      innovative substances act as true bone graft substitutes, thereby allowing the
      surgeon to avoid the use of autogenous bone grafts and their associated donor
      site morbidity. Surgeons have long been interested in producing a composite graft
      that can heal faster by induction, incorporate with surrounding tissues, and be
      remodeled to resemble native bone. Currently, there are a host of bone graft
      substitutes available that vary in both their composition and properties.
      Craniomaxillofacial surgeons must therefore become comfortable with numerous
      biomaterials to best tailor the treatment for each patient individually. Ongoing
      investigations into the next phase of tissue engineering will continue to bring
      us closer to the ability to regenerate or replace bone.

PMID- 11823930
TI  - Current applications of platelet gels in facial plastic surgery.
AB  - The response of living tissue to injury is a central component in the planning of
      all surgical procedures. The wound-healing process is typically divided into
      three phases (inflammatory, proliferative, and remodeling) and is a complex
      process in which a multitude of cellular and humoral components interact to
      restore a wound defect. Platelets and their released cytokines and growth factors
      are pivotal in the modulation of this entire process. Although several techniques
      may be used to achieve hemostasis after initial injury, few initiate and actually
      accelerate tissue regeneration. Both platelet gel and fibrin glue are effective
      hemostatic agents. Platelet gels, unlike fibrin glue, have a high concentration
      of platelets that release the bioactive proteins and growth factors necessary to
      initiate and accelerate tissue repair and regeneration. In particular, two growth
      factors that play a major role in platelet gels are platelet-derived growth
      factor, a powerful chemoattractant, and transforming growth factor beta, which
      significantly increases and stimulates the deposition of extracellular matrix. In
      creating a platelet gel, autologous blood is centrifuged to produce a concentrate
      high in both platelets and plasma. This concentrate can be applied to wounds,
      providing hemostasis, adhesion, and enhanced wound healing. Recent techniques for
      the autologous concentrating process have been streamlined, and now platelet gels
      are clinically accessible to most physicians. Platelet gels have global
      applications in surgery and are especially useful for the soft tissue and bony
      reconstructions encountered in facial plastic and reconstructive surgery. In
      these applications, their use has been associated with a decrease in operative
      time, necessity for drains and pressure dressings, and incidence of
      complications. When applied to bony reconstruction it provides adhesion for the
      consolidation of cancellous bone and comminuted fracture segments.

PMID- 11823931
TI  - Botulinum toxin to minimize facial scarring.
AB  - Botulinum toxin injection has been used for a variety of indications in humans,
      including blepharospasm and hyperfunctional facial lines. This article describes
      a novel formulation of botulinum toxin, which supplies immediate feedback to the
      injecting physician. Additionally, recent findings are described that indicate
      the immediate injection of botulinum toxin into the muscles underlying a wound
      can improve the cosmetic outcome of the facial cutaneous scar. Future
      applications of these findings are discussed.

PMID- 11823932
TI  - Growth factor therapy to improve soft tissue healing.
AB  - The advent of new U.S. Food and Drug Administration-approved products containing
      growth factors to improve soft tissue healing signifies a new era for wound
      healing. Over the last decade, some clinical growth factor studies have been
      promising, whereas others have not shown any positive effect. What many of these
      studies have shown is that the state of a healing wound is not only dependent on
      its growth factor milieu but also on other variables (wound care, tissue oxygen
      state, bacteria count, and nutritional status of the patient). This article
      describes recent progress with growth factors on soft tissue structures (skin,
      mucosa, and nerve) relevant to the facial plastic and reconstructive surgeon.

PMID- 11823933
TI  - Gene therapy, electroporation, and the future of wound-healing therapies.
AB  - Chronic wounds are a major clinical problem with notable morbidity. Treatment is
      usually supportive and results in significant healthcare expenditures. It is
      estimated that 1.25 million people are burned each year in the United States and
      that 6.5 million have chronic skin ulcers caused by pressure, venous stasis, or
      diabetes mellitus. Wound healing is a complex and lengthy process, often taking
      up to 12 months to complete. The cost of treating poorly healing foot wounds in
      the United States has been estimated at $1 billion per year. A number of topical
      commercial products have become available to provide an optimal environment for
      problematic open wounds. Topical platelet-derived growth factor (PDGF)-BB has
      proven effective in improving healing in impaired wounds but has the disadvantage
      of requiring large and repeated doses. More recently, investigators have focused
      on the possibility of inserting genes encoding for growth factors such as PDGF-BB
      into the cells participating in the wound-healing response. This approach offers
      the potential of single-dose growth factor treatment of chronic wounds. There are
      several approaches for gene insertion, including viral vectors, gene guns, and
      electroporation. This article reviews the strategies and potential of these
      approaches, with a focus on electroporation.

PMID- 11823934
TI  - Tissue engineering with chondrocytes.
AB  - Tissue engineering of cartilage, using chondrocytes based on the use of synthetic
      biodegradable polymer cell delivery vehicles (scaffolds), is an alternate
      treatment modality for replacing missing cartilage. Cartilage tissue engineering
      has an important role to play in the generation of graft material for head and
      neck reconstruction. It is an approach to fabricate cartilage constructs in
      vitro, which could be used in reconstructive surgery. Methods involve (1)
      harvesting septal cartilage during septoplasty, (2) isolating chondrocytes
      through enzymatic digestion of the septal cartilage, (3) expanding the cell
      number in a two-dimensional monolayer culture, using serum-free media, (4)
      seeding the cells onto a biodegradable polymer scaffold, and (5) cultivating the
      seeded scaffolds in a rotating bioreactor. In this article we briefly outline the
      methodology and clinical applications of cartilage grown ex vivo.

PMID- 11823935
TI  - Vascularized fibular osteocutaneous grafts in the treatment of severely infected
      wrist arthritis.
AB  - The authors successfully treated two cases of wrist arthritis severely infected
      by Staphylococcus aureus and Mycobacterium tuberculosis with vascularized fibular
      osteocutaneous grafts. The surgical procedure was divided into two stages, with
      extensive debridement of the infected wrist joint, and reconstruction with a
      vascularized fibular osteocutaneous flap. This two-staged surgery yielded
      complete amelioration of the severely infected wrist arthritis, and permanent
      stabilization of the wrist joint.

PMID- 11823936
TI  - Pre-, intra-, and postoperative electrophysiologic analysis of the recovery of
      old injuries of the peripheral nerve and brachial plexus after microsurgical
      management.
AB  - This prospective electrophysiologic study compares the analysis of the pre-,
      intra-, and postoperative results of 38 surgically treated patients suffering
      from old injuries of the peripheral nerve (n=28) and brachial plexus (n=10). The
      period from injury until surgery for the peripheral nerve group ranged from 1.2
      to 50 years and, in the brachial plexus group, from 1.2 to 12 years. A
      statistical electrophysiologic analysis was done: 1) to compare intraoperative
      amplitude and latency changes of the compound muscle action potential (CMAP) at
      commencement and on completion of surgery; 2) to compare amplitude and latency
      changes of CMAP and recruitment (voluntary muscle activity) prior to and 1 year
      after surgery. In the peripheral nerve group, intraoperative electrophysiologic
      recordings of CMAP showed a low amplitude at the onset of surgery and significant
      increase on completion of surgery after neurolysis (p=0.0001) with improvement of
      latency (p=0.001). The statistical analysis of recruitment of muscles showed a 60
      percent improvement 1 year after neurolysis (27 patients) and good recovery after
      nerve graft (1 patient). There were no statistically significant differences in
      results in patients under 40 years of age, compared to those above 40 years of
      age. In the brachial plexus group, statistical analysis of recruitment showed
      voluntary muscle activity in 45 percent of muscles 1 year after neurolysis (7
      patients) and in 42 percent of muscles after nerve graft and neurotization (3
      patients). Intraoperative electrophysiologic findings provide useful information
      during surgery for old peripheral nerve and brachial plexus injury.
      Intraoperative and postoperative electrophysiologic analyses suggest that the
      viability of the old injured nerve tissue is longer than previously considered,
      thus providing a longer period of time in which nerve recovery can occur.

PMID- 11823937
TI  - Microvascular toe transfer for cleft-foot plasty: eight-year follow-up.
AB  - No exact equivalent procedure has been developed for cleft-foot plasty. In the
      case of a four-year-old boy, the plasty was achieved by using microvascular toe
      transfer from a contralateral side that was amputated. Eight years
      postoperatively, the longitudinal growth of the grafted toe is symmetric,
      compared to the recipient toes, and the appearance of the treated foot is quite
      natural. The patient can run with a prosthesis on the amputated leg. It is
      suggested that utilization of parts from a useless extremity is important to
      reconstruct the other extremity.

PMID- 11823938
TI  - Pedicled foot fillet flap based on the tibialis anterior vessels: case report.
AB  - A case of an 18-year-old male with extensive posterior and lateral soft-tissue
      loss of the lower leg is reported. There was a segmental defect of 20 cm in the
      tibialis posterior neurovascular bundle, and the injury was not considered
      reconstructable. There was extensive soft-tissue trauma to the posterior
      compartments of the leg, with an intact and well-perfused foot. A primary
      amputation was indicated. The foot was used as a fillet flap for tibial length
      preservation and optimal stump coverage. The foot fillet flap was pedicled on the
      tibialis anterior vessels, preserving the deep plantar, first dorsal metatarsal,
      and anterior communicating vessels. The postoperative evolution was uneventful,
      with successful prosthetic adaptation.

PMID- 11823940
TI  - Clinical use of nerve conduits in peripheral-nerve repair: review of the
      literature.
AB  - The use of nerve conduits has evolved from a previous experimental idea to a
      clinical reality over the last ten years. An overview of the literature on the
      clinical use of nerve conduits in peripheral-nerve repair is presented.

PMID- 11823939
TI  - Valgus deformity of the ankle following harvesting of a vascularized fibular
      graft in children.
AB  - Progressive valgus ankle deformity is a problematic postoperative donor-site
      morbidity of a vascularized fibular graft in children. To prevent this
      complication, tibiofibular metaphyseal synostosis (the Langenskiold procedure)
      has been recommended. The authors objectively evaluated the preventive and
      therapeutic effects of this procedure on five children who had received free
      vascularized fibular grafts. Their average age at the time of operation was 3
      years (range: 1 to 9 years). The Langenskiold procedure was performed primarily
      in four patients, and not in one patient. The anteroposterior (A-P) mortise angle
      and the empirical axis of the donor-site ankle were measured radiographically.
      With regard to the A-P mortise angle, four of five patients showed valgus with a
      mild lateral wedging of the distal tibial epiphysis. The patient who did not
      receive the operation showed the largest A-P mortise angle and mild
      osteoarthritic changes. The empirical axis exceeded normal range in all of the
      five patients. These observations indicated that valgus deformity of the ankle in
      children after harvesting a vascularized fibular graft is inevitable, even if the
      Langenskiold procedure is performed. The procedure can delay the ankle valgus.
      The authors recommend close follow-up of the children who receive the
      Langenskiold procedure after harvesting a vascularized fibular graft.

PMID- 11823941
TI  - Assessment of the patency of microvascular venous anastomosis.
AB  - There is an absence of data on the timing of occlusion of vessels after
      anastomosis, and on the possible subsequent reopening (recanalization) of these
      vessels. This lack of information may be an important factor in the wide
      discrepancies found among reported patency rates for laboratory microvascular
      repair. In this study, a total of 300 standard microsurgical anastomoses were
      performed on rat femoral veins. The patency of each anastomosis was assessed at
      regular intervals within a 2-week study period. These results showed that the
      majority of venous occlusions occurred within 1 day after repair. Recanalization
      of the occluded vein was first seen at day 3 postoperatively. Recanalization was
      observed over a 2-week postoperative period with increasing frequency. The
      authors conclude that the optimal time to assess the technical outcome of
      experimental venous patency is 1 to 2 days after the repair.

PMID- 11823942
TI  - Effect of hyperthermic preconditioning on the survival of ischemia-reperfused
      skin flaps: a new skin-flap model in the mouse.
AB  - To investigate whether hyperthermic preconditioning can actually protect skin
      flaps against ischemia/reperfusion injury, the authors first developed a new skin
      flap model in 15 mice, a dorsal bipedicle island skin-flap model. Then, another
      75 mice were separated into five groups. Mice in Groups 1 to 4 received the same
      hyperthermic preconditioning, but had different recovery times of 6 hr, 24 hr, 48
      hr, and 72 hr, respectively. Mice in Group 5 served as control. Island skin flaps
      were elevated in all groups, and then were subjected to 8 hr of ischemia and
      subsequent reperfusion. Flap survival was statistically significantly higher than
      in controls in animals in Groups 1 and 3, with recovery times of 6 hr and 48 hr,
      respectively. Mice in Groups 2 and 4 had recovery times of 24 hr and 72 hr,
      respectively. Hyperthermic preconditioning could thus protect skin flaps against
      ischemia/reperfusion injury, and there were two optimal periods for such a
      protective effect.

PMID- 11823943
TI  - Secondary transplantation following a period of isografting: experimental study
      in rats.
AB  - The authors describe a study in which groin flaps from 20 Wistar rats were
      transplanted to another group of 20 Wistar rats and, after various time
      intervals, the groin flaps were re-transplanted back to the original animals. The
      goal of the first transfers was to preserve the flap in the second group of
      animals (isopreservation). During the isopreservation period, the second rat (the
      preserver) was treated with steroids or FK506 for immunosuppression. Thirty-three
      free groin flap transfers were performed between 40 rats. If possible, the same
      flap was transferred twice between two animals, one as an isograft, and other as
      an autograft following an isopreservation period in 13 pairs of animals. (A
      second transfer was not possible in seven pairs of animals.) The period for
      isopreservation varied between 2 days and 1 week. The survival of the flap was
      observed by visual inspection, laser Doppler flowmeter measurements, and was
      correlated with serial histopathologic examinations of skin and vessel biopsy
      specimens, including the anastomosis site. The severity of histopathologic signs
      that might be related to developing rejection was increased by the preservation
      time, and was more noticeable after the second transfer. The authors showed that
      successful secondary transplantation of the rat groin flap with a 1-week follow
      up could be achieved, following isopreservation of at least up to 5 days.

PMID- 11823945
TI  - Comparison of tensile strength and thrombus formation between mechanical
      microvascular anastomoses using a biodegradable ring device and sutured
      anastomoses.
AB  - The purpose of this study was to evaluate whether early motion following
      mechanical anastomosis using a biodegradable ring device was possible or not, by
      measuring tensile strength and the rates of thrombus formation at anastomotic
      sites. Bilateral femoral arteries and veins of 24 rabbits were repaired by
      sutured anastomoses and biodegradable ring anastomoses. The tensile strength of
      the anastomotic site was measured by constant loading with a material-testing
      machine, using specimens excised at 24 hr, 72 hr, 1 week, and 2 weeks after
      anastomosis. The tensile strength of biodegradable ring arterial anastomoses was
      significantly stronger than sutured anastomoses at 24 hr, 72 hr, 1 week, and 2
      weeks. No statistically significant differences were observed in venous
      anastomoses at any interval. In separate experiments, biodegradable ring
      anastomoses and sutured anastomoses of the bilateral femoral arteries of 18
      rabbits were constructed, and early passive knee motion was carried out at 100
      times once a day with maximum spreading of the hip joint for 24 hr, 72 hr, and 1
      week. Thrombus formation at the anastomotic sites was evaluated by scanning
      electron microscope (SEM). SEM showed no thrombus formation in the biodegradable
      ring anastomoses at any interval; however, thrombi were observed in the sutured
      anastomoses (33 to approximately 50 percent).

PMID- 11823948
TI  - [Telemedicine in pediatric oncology].
AB  - The telemedicine project of the Competence Net Pediatric Oncology of the
      German/Austrian Gesellschaft fur Padiatrische Onkologie und Hamatologie (GPOH)
      has as an initial step of its work-programme sent out a questionnaire to the 54
      largest pediatric hematology/oncology units in Germany. Institutions were asked
      for their experience, motivation, existing infrastructure, and anticipated
      benefits and obstacles regarding the implementation of telemedicine in patient
      care and research. Of the 54 largest German Pediatric Oncology institutions
      asked, 46 completed the questionnaire (85 %). RESULTS: 1. The need for further
      detailed information on implementation and for help in technical realization of
      telemedicine applications was expressed by all participants. 2. The majority
      expected practical advantages from telemedicine communication and anticipated
      that telemedicine will increase quality in treating children with cancer. 3.
      Expert consultation (study chairman, reference radiologists) is stated as to be
      most important. 4. Thirty-three of 46 physicians (72 %) believe that telemedicine
      will reduce costs in medical care within the next years. 5. It is anticipated
      that the introduction of telemedicine is time consuming. 6. The lack of available
      medical informatics competence and manpower was regarded as the most important
      obstacle. 7. Data security and standardization, transfer speed and transmission
      quality are considered most important. 8. Most of the institutions (91 %) use
      computers in the management of patients. Fourty-four (96 %) are connected to the
      Internet. 9. Thirty-seven of 46 institutions were prepared to invest in the
      implementation of telemedicine. This analysis demonstrates that the use of
      telemedicine is expected to become standard in pediatric oncology, while the
      existing infrastructure and status of information regarding this subject at
      present are insufficient. The most pressing practical need for telemedicine
      applications is seen in the field of electronic expert consultation. Hence, the
      Telemedicine-Project of the GPOH Competence Net will focus on this aspect first.

PMID- 11823947
TI  - Protein content and biophysical properties of tracheal aspirates form neonates
      with respiratory failure.
AB  - BACKGROUND: We aimed at assessing the quality and quantity of protein-leakage
      across the alveolar-capillary membrane and its influence on surfactant function
      during the early neonatal period in preterm infants compared to newborns both
      with respiratory failure. PATIENTS AND METHODS: We therefore prospectively
      analyzed total protein, elastase-alpha1-proteinase inhibitor complex (E-alpha1
      PI) and alpha2-macroglobulin concentrations in tracheal aspirates from 31 infants
      < or = 32 weeks gestational age (group 1 : 29.3 +/- 2 weeks, 1214 +/- 410 g
      [means +/- SEM]) and from 21 neonates > 32 weeks (group 2 : 37.5 +/- 3 weeks,
      2890 +/- 600 g [means +/- SEM]) and measured their surface activity in the
      pulsating bubble surfactometer. RESULTS: Day 1 total protein and alpha2
      macroglobulin levels indicated an initial high leakage that declined to day 3 in
      both groups (from 1652 +/- 241 to 708 +/- 227 mg/l; p < 0.05; resp. from 28 +/- 6
      to 12 +/- 4 mg/l [means +/- SEM]). In group 2 E-alpha1-PI concentrations were
      significantly elevated at day 1 compared to group 1 (15 754 +/- 5766 versus 3320
      +/- 1056 microg/l [means +/- SEM]). In both groups a high minimum surface tension
      (15 - 30 mN/m) was recorded from day 1 - 4. CONCLUSIONS: These results suggest in
      larger newborns a secondary surfactant deficiency due to protein-leakage to play
      an important role in the pathogenesis of respiratory failure. The increased
      alveolar-capillary membrane permeability might be caused by inflammatory ARDS
      like mechanisms.

PMID- 11823949
TI  - [Hereditary deficiency of C1-esterase inhibitor presenting with recurrent
      abdominal pain].
AB  - Hereditary deficiency of C1-esterase inhibitor (C1-INH) which clinically
      manifests as hereditary angioedema is a rare disorder. In previously not
      diagnosed cases, a fatality rate of up to 30 % has been reported. The diagnosis
      of C1-esterase inhibitor deficiency should not be missed in patients presenting
      with angioedema in the face, stem or extremities. We report the case of a 17-year
      old girl with recurrent abdominal pain and swelling of the hands.

PMID- 11823950
TI  - [Neuropsychological sequelae in children with AML treated with or without
      prophylactic CNS-irradiation].
AB  - BACKGROUND: In study AML-BFM 87 the relapse rate was lower in patients receiving
      cranial irradiation (CRT). However, CRT has always been associated with adverse
      cognitive side effects. Therefore, the impact of CRT on neuropsychological
      function in children with AML was retrospectively evaluated. PATIENTS: We tested
      53 children (30 boys, 23 girls) treated according to the AML-BFM-87 protocol
      (median age at diagnosis: 8.5 years, range 0.3 - 17.5; median time since
      diagnosis: 5.7 yrs, 3.8 - 10.7 yrs). To avoid any bias from additional therapy
      elements, patients with relapse or initial CNS involvement and transplanted
      patients were excluded (n=32). Our cohort was representative of the total group
      of 104 long term survivors of study AML-BFM 87. CNS prophylaxis consisted of ARA
      C i.th., high dose ARA-C i. v. and either no CRT (n=15) or CRT (n=38) at a dose
      of 12 - 18 Gy depending on age. METHODS: Neuropsychological function was
      evaluated by psychological tests of attention and concentration (test d2 by
      Brickenkamp) and an intelligence test (Progressive Matrices by Raven). In
      addition, patients and their parents were interviewed about the occurrence of
      learning problems, subjective deficits in concentration and physical impairment.
      RESULTS: In the total group, no significant differences were seen between
      irradiated and non-irradiated patients regarding the psychological tests.
      However, the irradiated patients scored below the non-irradiated control group in
      test "d2" (concentration: 41st vs. 59th percentile). In the interview, irradiated
      patients tended to report more learning problems (lp) (10/36 vs. 1/14; p=0.15)
      and subjective deficits in concentration (con). In irradiated girls (con: 6/15
      vs. 0/8; p=0.06; lp: 5/15 vs. 0/8; p=0.12) and younger patients (0 - 5 years at
      diagnosis; con: 7/12 vs. 2/9; p=0.18; lp 3/10 vs. 1/9; p=0.18) this trend was
      even more pronounced. CONCLUSION: Children with AML and CRT had no significant
      intellectual impairment in standardized tests when compared to non-irradiated
      patients. However, more irradiated patients reported learning problems and
      subjective concentration deficits.

PMID- 11823951
TI  - [A postmortem view on "pure" subdural hemorrhages in infants and toddlers].
AB  - In the last years, the discussion concerning the causes of infantile subdural
      hemorrhages became controversial. Many authors still suppose that child abuse is
      the predominant cause of such cases. On the other hand, reports presenting series
      of accidental cases were published, and the fear of an overdiagnosis of the
      shaken baby syndrome has been expressed. Our autopsy material concerning all
      lethal head injuries of infants and toddlers from 2 decades was reviewed. 17 of
      these 64 cases were characterized by the following: history of no trauma or only
      an insignificant event; children found dead or apnoic or in coma; no skull
      fractures; no focal brain injury; ruptures of several bridging veins but only
      minimal subdural bleeding. 11 victims were infants (1st year of life) and either
      3 were 2 years resp. 3 - 6 years old; 50 % off all lethal head injuries of
      infants were of this type, while only 25 % resp. 10 % of the following age
      groups. None of these 17 cases was a result of a minor accident witnessed by
      unrelated persons. Abuse could be ascertained with a high degree of probability
      in most cases and remained quite likely in the others. Two different types of
      subdural hemorrhages should be kept from another: a) patients suffering a
      moderate head injury from a minor accident which results in a subdural bleeding
      (from a small intracranial lesion) often do not deteriorate soon after the
      impact, develop a hemorrhage of significant volume, respond well to therapy and
      have a good prognosis. b) cases with a history of no or only of an insignificant
      trauma, infants dead or nearly dead on clinical presentation, often a poor
      outcome in cases of survival. There is typically no significant subdural bleeding
      despite multiple bridging vein ruptures in the majority of these cases: the
      subdural hemorrhage is here only a visible sign of a much more serious and
      general cerebral alteration, resulting in a rapid increase of intracranial
      pressure (often complicated by respiratory arrest) which prevents a signifant
      bleeding into the subdural space. This combination of findings is typically found
      in victims of massive events (car occupants in high-velocity crashes) and not
      compatible with a supposition of a minor fall causing this.

PMID- 11823952
TI  - [Treatment of infants with RSV infection: a retrospective analysis of the season
      1998/99].
AB  - Respiratory syncytial virus (RSV) is the most frequent cause of hospitalization
      for respiratory tract infection during the first 2 years of life. Recently the
      monoclonal antibody Palivizumab was approved for prophylaxis of RSV infection.
      Guidelines for the use of Palivizumab are based on data from North America and
      Great Britain. The epidemiology of RSV infection and patient management
      procedures may vary from one country to another. This study was designed to
      analyze the spectrum of patients hospitalized in Germany for RSV infection.
      During the 1998 to 1999 RSV season RSV-infected children admitted to twenty
      hospitals were followed. Of 222 RSV-infected patients 17.6 % (39) were born at 32
      weeks of gestation or earlier and 16.2 % (36) between 33 weeks and 35 weeks.
      There were significant differences (P < 0.01) between the extremely preterm
      infants and the other patients in frequency of bronchopulmonary dysplasia,
      supplemental oxygen and age at hospital admission. In addition, both preterm
      groups had a significant longer length of hospital stay compared to the infants
      born at term. Thus, the current guidelines seem to be appropriate for selection
      of infants to receive RSV prophylaxis.

PMID- 11823953
TI  - [Cavernoma of the medulla oblongata mimicking "Anorexia nervosa" - a case
      report].
AB  - An 11-year-old girl presented with recurrent vomiting, reduced food and fluid
      intake, weight loss and dizziness. In an external hospital she was diagnosed as
      having habitual vomiting and a beginning eating disorder. The physical
      examination revealed a very thin, malnourished child with abdominal pain on
      palpation but without neurologic deficits. Laboratory findings, X-rays, endoscopy
      and ultrasound revealed no pathological results either. Since the EEG and the
      cranial computed tomography (CT) were normal, we also suspected the beginning of
      an eating disorder especially due to some psychical peculiarities. The MRI which
      was done for ultimate exclusion of an infratentorial tumor showed a well defined
      displacing structure in the dorsal medulla oblongata and in the upper cervical
      spinal cord. A corresponding prolongation of the central conduction time was
      found in the median nerve SSEP whereas the BAEPs were normal. The tumor was
      excised in toto and the histological examination confirmed the suspected
      diagnosis of cavernous hemangioma (cavernoma). The post operative phase was
      without any complications and the intiated nutrition was well tolerated.
      Neurological deficits were not observed.

PMID- 11823954
TI  - Multiple mechanisms of antimicrobial resistance in Pseudomonas aeruginosa: our
      worst nightmare?
AB  - Pseudomonas aeruginosa carries multiresistance plasmids less often than does
      Klebsiella pneumoniae, develops mutational resistance to cephalosporins less
      readily than Enterobacter species, and has less inherent resistance than
      Stenotrophomonas maltophilia. What nevertheless makes P. aeruginosa uniquely
      problematic is a combination of the following: the species' inherent resistance
      to many drug classes; its ability to acquire resistance, via mutations, to all
      relevant treatments; its high and increasing rates of resistance locally; and its
      frequent role in serious infections. A few isolates of P. aeruginosa are
      resistant to all reliable antibiotics, and this problem seems likely to grow with
      the emergence of integrins that carry gene cassettes encoding both carbapenemases
      and amikacin acetyltransferases.

PMID- 11823955
TI  - Field evaluation of the Merlin immediate HIV-1 and -2 test for point-of-care
      detection of human immunodeficiency virus antibodies.
AB  - The Merlin Immediate HIV-1 and -2 Test (Merlin point-of-care [POC] test; Merlin
      Biomedical & Pharmaceutical) is a nitrocellulose membrane flow immunoassay
      performed at the POC with the use of blood obtained from a fingerprick. The
      results of this test were compared with those of enzyme immunoassay (EIA)
      performed on venous blood samples in the laboratory. Positive results of both
      tests were confirmed by a Western blot (WB). The study included 553 adults with
      known HIV (human immunodeficiency virus) seropositivity (all of whom had positive
      Merlin POC test results) and 2659 adults with unknown HIV serostatus (20 of whom
      had positive EIA/WB results; 19 of the 20 also had positive Merlin-POC test
      results). The sensitivity of the Merlin POC test was 95.0% for patients with an
      unknown HIV serostatus and 99.83% for those with a positive serostatus. For
      previously untested subjects, the test's specificity and positive predictive
      value were 100%, its negative predictive value was 99.96%, and its overall
      accuracy was 99.96%. The Merlin POC test is highly accurate for the detection of
      HIV antibodies.

PMID- 11823956
TI  - Nosocomial bloodstream infections among human immunodeficiency virus-infected
      patients: incidence and risk factors.
AB  - To assess the incidence of nosocomial bloodstream infections (NBSIs) in human
      immunodeficiency virus (HIV)-infected patients, and to analyze the main
      associated risk factors, we performed a 1-year multicenter prospective study of
      patients with advanced HIV infection who were consecutively admitted to 17
      Italian infectious diseases wards. As of May 1999, a total of 65 NBSIs (4.7%)
      occurred in 1379 admissions, for an incidence of 2.45 NBSIs per 1000 patient
      days. Twenty-nine NBSIs were catheter-related bloodstream infections, with a rate
      of 9.6 central venous catheter-associated infections per 1000 device-days.
      Multivariate analysis indicated that variables independently associated with
      NBSIs included active injection drug use, a Karnofsky Performance Status score of
      <40, presence of a central venous catheter, and length of hospital stay.
      Mortality rates were 24.6% and 7.2% among patients with and without NBSIs,
      respectively (P<.00001). In the era of highly active antiretroviral therapy,
      NBSIs continue to occur frequently and remain severe and life-threatening
      manifestations.

PMID- 11823957
TI  - Daily dosing of highly active antiretroviral therapy.
AB  - Complex treatment schedules for human immunodeficiency virus (HIV) disease, which
      can have a high pill burden and can include multiple daily doses, in addition to
      the adverse effects that the medications can cause, may reduce patient adherence
      to therapy. Reduced adherence prevents achievement of the desired goal of full
      suppression of HIV replication, and it also promotes the development of drug
      resistant strains of HIV. Thus, the focus of treatment has shifted toward the use
      of simpler regimens. A major strategy is the development of medications and
      regimens for management of HIV infection that can be taken once per day. The goal
      of such a strategy is to improve convenience and optimize adherence, which is
      critical to maximizing the likelihood of sustained virologic response. Several
      studies involving regimens with once-daily dosing, which have involved both
      available agents and agents in development, have yielded promising results. In
      comparison with standard regimens, which involve dosing 2 or 3 times daily, the
      regimens with once-daily dosing improved tolerability while maintaining efficacy
      and safety. The results are expected to increase adherence rates among patients,
      reduce the incidence of antiretroviral-resistant variants of HIV, and improve the
      clinical outcomes during a prolonged treatment course.

PMID- 11823958
TI  - Cross-linked fibrin in the nasal fluid of patients with the common cold.
AB  - To determine whether adherent material found on the walls of the paranasal
      sinuses during common colds might be fibrin clot, we examined the nasal fluid (a
      surrogate for sinus secretion) of 11 young adults with experimentally induced
      rhinovirus colds and that of 4 control subjects for the presence of fibrin. The
      mean concentration (+/- the standard error) of insoluble fibrin (measured as D
      dimer) in subjects with rhinovirus colds increased from a baseline level of 0.8+/
      0.4 microgram/mL to a peak of 2.4+/-0.7 microgram/mL (P=.0008) on day 4 after
      inoculation of the virus, but the fibrin concentration remained at baseline
      levels in the 4 uninfected control subjects.

PMID- 11823959
TI  - Acanthosis nigricans: a new manifestation of insulin resistance in patients
      receiving treatment with protease inhibitors.

PMID- 11823960
TI  - Seroreversion from hepatitis C after needlestick injury.

PMID- 11823961
TI  - Campylobacter species: don't put all your eggs in one chicken.

PMID- 11823963
TI  - The role of cefoperazone-sulbactam for treatment of severe melioidosis.

PMID- 11823966
TI  - Pathology--Medicine's search for meaning in the new millennium.

PMID- 11823965
TI  - Clostridium difficile infection in patients with neutropenia.

PMID- 11823967
TI  - Trends in pathology education.

PMID- 11823968
TI  - Competency-based residency training in pathology: challenges and opportunities.
AB  - The Accreditation Council for Graduate Medical Education (ACGME) is requiring
      that all medical specialties adopt a new paradigm for residency education:
      competency-based residency education. Competency-based education includes not
      only the acquisition of knowledge and the demonstration of safe medical practice,
      but also competency in practice-based learning, practice improvement,
      interpersonal skills and communication, professionalism, and an awareness of
      pathology's role in a larger health care system. Implementation of this new
      training program will require new educational resources and the implementation of
      new faculty and resident skills and incentives.

PMID- 11823969
TI  - From centrocytic to mantle cell lymphoma: a clinicopathologic and molecular
      review of 3 decades.
AB  - Mantle cell lymphoma (MCL), described almost 3 decades ago as centrocytic
      lymphoma and by a variety of other names, was initially recognized
      morphologically. MCL is a classic illustration of how the field of
      hematopathology and our basic understanding of neoplasia have evolved. The advent
      of immunophenotypic and increasingly sophisticated genotypic and cytogenetic
      studies, together with clinical investigations, have led to a better practical
      and biologic understanding of MCL and have broader implications as well. MCL is
      now recognized as an aggressive, difficult to treat, B-cell lymphoma with a
      broader morphologic spectrum than was initially appreciated and a characteristic
      phenotype (CD5+, CD10-, CD23-, FMC7+). Virtually all MCLs carry the translocation
      t(11;14)(q13;q32) with overexpression of the involved CCND1 (cyclin D1) gene.
      Additional cytogenetic and molecular abnormalities have been identified,
      including some that are early events (such as ATM gene deletion and mutation) and
      others that appear to be late events (such as deletions and mutations in the
      negative cell cycle regulatory elements p53, p16, and p18). The latter are often
      associated with a blastoid morphology and more aggressive clinical course.
      Ongoing clinical and basic investigations including microarray analysis will
      undoubtedly provide additional insights into MCL and perhaps more effective and
      specific therapeutic modalities.

PMID- 11823970
TI  - Protein overexpression and gene amplification of c-erbB-2 in breast carcinomas: a
      comparative study of immunohistochemistry and fluorescence in situ hybridization
      of formalin-fixed, paraffin-embedded tissues.
AB  - We evaluated 173 consecutive breast carcinomas for c-erbB-2 using a combination
      of immunohistochemistry (IHC) with a commercial polyclonal antibody (Nitirei) and
      dual-color fluorescence in situ hybridization (FISH) using the c-erbB-2-specific
      probe and the chromosome 17 centromere-specific probe from Vysis (Downers Grove,
      IL) and compared the results with the histologic characteristics of intraductal
      spread, cancer invasion, and intratumoral heterogeneity. With correction for
      chromosome 17 copy number, c-erbB-2 amplification was observed in 26 tumors
      (13.5%): high-level amplification in 23 tumors, and low-level amplification in 3.
      The gene amplification was positively correlated with c-erbB-2 protein
      overexpression, defined as 2+ or 3+ immunostaining, on a case-by-case basis (P <
      .000001). All 3+ immunostaining tumors (19 tumors) showed high-level
      amplification, although gene amplification was found in only 5 of 27 2+
      immunostaining tumors. Although the rates of overexpression and gene
      amplification did not differ in ductal carcinomas in situ and invasive carcinomas
      (P = .46 and .53, respectively), they were significantly higher in invasive
      carcinomas with intraductal spreading (P < .0001). Intratumoral heterogeneity of
      c-erbB-2 amplification was found in only 1 case; however, in 17 invasive
      carcinomas, intraductal components expressed c-erbB-2 more intensely than
      invasive components. We conclude that in breast carcinomas, c-erbB-2
      overexpression occurs mostly in tumors with high-level gene amplification, and
      such overexpression appears to endow carcinoma cells with the capacity for
      intraductal spreading. The best method for detecting breast carcinomas with c
      erbB-2 aberrations using archival tissues is to screen cases by IHC; however,
      follow-up FISH assays are indispensable for excluding false-positive results.

PMID- 11823971
TI  - Radial scars of the breast and breast carcinomas have similar alterations in
      expression of factors involved in vascular stroma formation.
AB  - We recently reported that radial scars are an independent histologic risk factor
      for breast cancer. The reason for this association is not known. Given the
      importance of stromal-epithelial interactions in the pathogenesis of breast
      cancer, we studied radial scars for the expression of a number of factors known
      to be involved in the formation of vascular stroma in breast cancer. In situ
      hybridization was performed on formalin-fixed paraffin sections using (35)S
      labeled riboprobes for collagen type 1, total fibronectin, extra domain A (ED-A)+
      fibronectin, thrombospondin 1, vascular permeability factor (VPF)/vascular
      endothelial growth factor (VEGF), and one of its endothelial receptors, kinase
      insert domain-containing receptor (KDR) (vascular endothelial growth factor
      receptor [VEGFR-2]). Expression levels in radial scars (9 cases) were compared
      with those in normal breast tissue (15 cases) and infiltrating ductal breast
      carcinoma (4 cases). Factor VIII-related antigen immunostaining was used to
      define the distribution of microvessels in radial scars, carcinoma, and normal
      breast tissue. Compared with normal breast tissue, the radial scars showed
      focally increased numbers of blood vessels and focally increased expression of
      messenger RNA (mRNA) for collagen type 1, total fibronectin, ED-A+ fibronectin,
      thrombospondin 1, VPF/VEGF, and KDR. This pattern of mRNA overexpression was
      similar to that seen in the 4 invasive cancers. We conclude that there are
      similarities between radial scars and invasive breast cancers with regard to the
      level of mRNA expression for several factors involved in the formation of
      vascular stroma. These results suggest that a similar disturbance in stromal
      epithelial interactions is present in both lesions.

PMID- 11823973
TI  - Micropapillary serous carcinoma of the ovary has distinct patterns of chromosomal
      imbalances by comparative genomic hybridization compared with atypical
      proliferative serous tumors and serous carcinomas.
AB  - Recent studies have subdivided serous borderline tumors into 2 categories:
      atypical proliferative serous tumors (APSTs), which have a relatively benign
      course, and micropapillary serous carcinomas (MPSCs), which behave like low-grade
      carcinoma. This study was undertaken to determine, using comparative genomic
      hybridization (CGH), whether cytogenetic changes support this hypothesis. Nine
      cases of APST, 10 of MPSC, and 11 of invasive serous carcinoma (SC) were analyzed
      by CGH. Tumor DNA was extracted from frozen or paraffin-embedded tissue from the
      primary ovarian tumor, using either sections with at least 70% tumor cells or
      tissue after relative enrichment by microdissection. Chromosomal imbalances were
      identified in 3 of 9 APST, 6 of 10 MPSC, and 11 of 11 SC. Three or more
      chromosomal imbalances were found in 0 of 9 APST, 4 of 10 MPSC, and 9 of 11 SC.
      Recurrent copy number alterations were grouped into 4 classes correlating with
      the different tumor types. Class I changes were present in APST and in MPSC or SC
      and included +8q (7 of 11 SC, 2 of 10 MPSC, 2 of 9 APST), -9p (5 of 11 SC, 0 of
      10 MPSC, 1 of 9 APST), and +12 (+12p in 3/11 SC, +12 in 2 of 10 MPSC, +12 in 1 of
      9 APST). Class II changes were found only in MPSC and SC, but not in APST. The
      most frequent examples were +3q (10 of 11 SC, 1 of 10 MPSC), -4q (5 of 11 SC, 1
      of 10 MPSC), and -17p (5 of 11 SC, 1 of 10 MPSC). Class III changes were limited
      to SC, like -16q (7 of 11 SC) and -18q (6 of 11 SC). Class VI changes were unique
      to MPSC. Gain of 16p (3 of 10 MPSC) was the only aberration in this group. This
      aberration was not only unique to MPSC but was also the most frequent finding in
      MPSC. These data support the hypothesis that noninvasive serous tumors of the
      ovary can be subdivided into 2 categories: APST and MPSC. The number of
      imbalances in MPSC is substantially higher than in APST and lower than in SC.
      Some changes in MPSC are shared with SC and APST and others with SC only,
      suggesting that a subset of MPSC may represent a stage in progression from APST
      to SC. Other cases of MPSC with independent genetic alterations may represent
      another subset of tumors that are a distinct entity from APST and SC.

PMID- 11823972
TI  - Fibromatosis of the breast and mutations involving the APC/beta-catenin pathway.
AB  - Fibromatoses of the breast are nonmetastasizing tumors, but can be infiltrative
      and locally recurrent. Breast fibromatoses are rare, and their specific genetic
      alterations have not been elucidated. However, their occasional occurrence in
      patients with familial adenomatous polyposis (FAP) and their morphologic
      identification with other deep fibromatoses (desmoid tumors) suggest that
      alterations of the APC/beta-catenin pathway might be involved in the pathogenesis
      of sporadic and FAP-associated breast fibromatoses. We analyzed somatic beta
      catenin and APC gene mutations in 33 breast fibromatoses (32 sporadic and 1 FAP
      associated) using immunohistochemistry for beta-catenin, 5q allelic loss assays,
      and direct DNA sequencing for exon 3 of the beta-catenin gene and the mutation
      cluster region of the APC gene. Nuclear accumulation of beta-catenin was present
      in the stromal tumor cells in most (82%) cases but not in normal stroma or
      mammary epithelial cells. Somatic alterations of the APC/beta-catenin pathway
      were detected in 79% of breast fibromatoses, including activating beta-catenin
      gene mutations in 15 cases and somatic APC alterations (mutation or 5q allelic
      loss or both) in 11. These findings indicate that alterations of the APC/beta
      catenin pathway with resultant nuclear translocation of beta-catenin are
      important in the pathogenesis of both sporadic and FAP-associated breast
      fibromatosis. The spectrum of beta-catenin and APC alterations is similar to that
      described for desmoid tumors of the abdomen, paraspinal region, and extremities.

PMID- 11823974
TI  - MUC1 mucin and trefoil factor 1 protein expression in renal cell carcinoma:
      correlation with prognosis.
AB  - This study examines the coexpression of MUC1 mucin and trefoil factor 1 (TFF1)
      and their relationship to progression of renal cell carcinoma (RCC).
      Immunohistochemistry was performed on tumor and adjacent normal tissue from clear
      cell RCC (n = 60) and tissues from normal controls (n = 5) using a set of well
      characterized monoclonal antibodies recognizing different epitopes of MUC1 and
      TFF1. Results of immunohistochemistry were compared with clinical parameters,
      including tumor grade, tumor size, presence of metastasis, and progression-free
      survival of patients after surgery. In normal tissue, MUC1 and TFF1 were absent
      from the normal proximal tubular epithelium but were identified in distal and
      collecting tubular epithelium. In RCC, increased MUC1 expression positively
      correlated to tumor progression. MUC1 recognized by HMFG1 was associated with
      large tumor size (P < .05), distant metastasis (P < .05), and invasion of large
      veins (P < .05). Expression of the under-glycosylated form of MUC1 recognized by
      SM3 was found to correlate to time to progression (recurrence, metastasis, or
      death of patient; P < .001). Expression of TFF1 did not significantly correlate
      with any prognostic parameters. However, there was a significant correlation (P <
      .01) between TFF1 and MUC1 expression (HMFG2 epitope) in RCCs. These results are
      consistent with the following conclusions: (1) MUC1 may be an independent
      prognostic marker in RCC; (2) TFF1 is frequently coexpressed with MUC1 and may
      act synergistically; and (3) RCC may originate from distal tubular epithelium.

PMID- 11823975
TI  - Renal epithelial neoplasms: the diagnostic implications of electron microscopic
      study in 55 cases.
AB  - Several unsettled histogenetic, nosologic and diagnostic considerations for renal
      epithelial tumors may have ultrastructural ramifications. Yet, a comprehensive
      electron microscopic study of renal epithelial neoplasms, in light of the recent
      classification, is not available. The ultrastructural findings from fifty-five
      renal epithelial neoplasms [31 clear cell renal cell carcinomas (RCC), 11
      papillary RCC, 5 chromophobe RCC, 3 sarcomatoid RCC and 5 oncocytomas] were
      correlated with their light microscopic appearance. Clear cell RCC showed long
      microvilli similar to the brush border of the normal proximal tubules, with
      abundant cytoplasmic lipid and glycogen. Papillary RCC showed variably sized
      microvilli, and small amounts of cytoplasmic lipid, but no glycogen. Chromophobe
      RCC showed many cytoplasmic vesicles and abnormal mitochondria, with rare short
      and stubby microvilli. Renal oncocytoma showed many mitochondria with a few
      vesicles in the apical portion of the cytoplasm and rare short and stubby
      microvilli. The eosinophilic cell variants of clear cell RCC, papillary RCC and
      chromophobe RCC showed ultrastructural features similar to those of their
      respective prototypes, except for an increased numbers of mitochondria in the
      cytoplasm. One sarcomatoid clear cell RCC showed skeletal muscle differentiation.
      Two types of cytoplasmic inclusions, i.e. hyaline globules and granules similar
      to those in the Paneth cells (PC-like granules) were identified only in clear
      cell RCC, which displayed distinctive ultrastructural features. The current EM
      study demonstrates distinctive ultrastructural features of renal epithelial
      neoplasms. The findings lend additional support to the current classification of
      the pertinent tumor types, facilitate the differential diagnoses, and provide
      insights into the possible histogenesis of renal epithelial neoplasms.

PMID- 11823976
TI  - Relationship between biologic behavior and phenotypic expression in intramucosal
      gastric carcinomas.
AB  - We investigated the biologic behavior of gastric phenotype carcinoma of the
      stomach, especially in association with degradation of the extracellular matrix.
      One hundred fourteen lesions of intramucosal gastric carcinoma (IMGC) of
      differentiated type were studied. IMGCs were classified into 4 phenotypic
      categories--complete intestinal type (C type), incomplete intestinal type (I
      type), gastric type (G type), and unclassified type--through a combination of the
      expression of CD10, MUC2, HGM, and Con A. The expression of MMP-2, MMP-9, TIMP-2,
      and type IV collagen was investigated by immunohistochemical staining. The
      incidence of C-type IMGC, I-type IMGC, and G-type IMGC was 7.9%, 55.3%, and
      36.8%, respectively. The incidence of positive MMP-9 expression in G-type IMGCs
      (57%) was significantly higher than that in C-type IMGCs (11%) or I-type IMGCs
      (35%) (P < .01). There was no significant correlation between phenotypes and
      expression of MMP-2, TIMP-2, or type IV collagen. There was a reverse correlation
      between the expression of type IV collagen and the expression of type IV
      collagenase (P < .001). In conclusion, gastric phenotype carcinomas have been
      shown to be highly invasive and metastatic, However, although they can
      potentially degrade the extracellular matrix via overexpression of MMPs compared
      with intestinal phenotype carcinoma, our data show no statistically significant
      separation of subtypes of intramucosal gastric cancer based on gross
      classification, histologic type, lymphatic or venous invasion, or lymph node
      metastases.

PMID- 11823977
TI  - Genetic alterations in serrated adenomas: comparison to conventional adenomas and
      hyperplastic polyps.
AB  - Serrated adenoma is a recently described entity characterized by the presence of
      a hyperplastic (serrated) growth pattern combined with cytologic features of
      dysplasia. In contrast to conventional (nonserrated) adenomas, the molecular
      features of serrated adenomas have been poorly studied. Thus, it remains unclear
      if serrated adenomas are simply a morphologic variant of conventional adenomas or
      represent a different biologic entity. In this study, 46 serrated adenomas from
      39 patients, 32 conventional (nonserrated) adenomas from 31 patients, and 18
      hyperplastic polyps from 16 patients were evaluated for loss of heterozygosity
      (LOH) of APC, p53, p16, and 3p and for K-ras mutations of codons 12, 13, and 61
      by polymerase chain reaction (PCR) analysis. Serrated adenomas demonstrated LOH
      of at least one genetic locus in 32.6% of cases. LOH of the APC gene, 3p, p53,
      and p16 was seen in 19.4%, 14.2%, 9.3%, and 13.8% of cases, respectively. K-ras
      mutations were observed in 18% of cases. Similar to serrated adenomas,
      conventional adenomas demonstrated at least one LOH event in 37.5% of cases and K
      ras mutations in another 19% of cases. LOH of APC, 3p, p53, and p16 was observed
      in 22%, 33%, 5.8%, and 13.4% of cases, respectively. There were no significant
      differences in either the total number of genetic events or the presence of LOH
      of any of the individual markers between serrated adenomas and conventional
      adenomas. However, hyperplastic polyps showed LOH in 22% of cases and a single K
      ras mutation (11%). The prevalence of LOH in hyperplastic polyps was lower than
      both serrated adenomas and conventional adenomas (P < .05). These results support
      the hypothesis that serrated adenomas represent a biologically similar
      morphologic variant of conventional adenomas.

PMID- 11823978
TI  - Simple tumor profile chart based on cell kinetic parameters and histologic grade
      is useful for estimating the natural growth rate of hepatocellular carcinoma.
AB  - Thirty-four untreated hepatocellular carcinomas (HCCs) with known growth rates
      were classified into 5 groups on a tumor profile chart based on their doubling
      time (DT), Ki-67-positive index (Ki-67-PI), apoptotic index (Apo-I), and
      histologic grade. The slow-growing HCCs (DT > 100 days) consisted of well
      differentiated tumors with slight cell kinetic imbalance and were divided into
      groups A and B. Group A had Apo-I values <3%, and most tumors had Ki-67-PI values
      <10%, whereas group B had Apo-I values of 3 per thousand to 10 per thousand and
      Ki-67-PI values of 10% to 20%. The HCCs with intermediate growth rates, which had
      Ki-67-PI values similar to those of the tumors in group B, were divided into
      groups C and D based on differences in cell kinetics: group C consisted of well
      differentiated tumors, most of which had Apo-I values <3 per thousand, and group
      D consisted of moderately or poorly differentiated tumors with Apo-I values
      between 10 per thousand and 20 per thousand. The rapidly growing tumors (DT < 50
      days, group E) had higher Ki-67-PI values than other groups and a wide range of
      Apo-I values. Rapidly growing tumors were mostly moderately or poorly
      differentiated, with a large cell kinetic imbalance in favor of cell production.
      This grouping system is useful for approximating the growth rate of HCCs in a
      clinical setting, even when only histologic parameters are available.

PMID- 11823979
TI  - Overexpression of cyclo-oxygenase 2 in squamous cell carcinoma of the
      hypopharynx.
AB  - Upregulation of cyclo-oxygenase 2 (COX-2) expression is frequently found in a
      variety of human cancers. In this study, we examined COX-2 expression in squamous
      cell carcinoma of the hypopharynx. COX-2 messenger RNA (mRNA) analyzed by reverse
      transcription polymerase chain reaction was detected in 87% (20 of 23) of tumor
      tissues. Expression of COX-2 protein was examined by Western blot analysis. COX-2
      protein levels were increased in tumor tissues and correlated with the expression
      level of mRNA. Immunohistochemical study was performed to detect the subcellular
      localization of COX-2. Our results showed that COX-2 was predominantly detected
      in cancer cells, and the staining pattern was cytoplasmic. Several histologically
      normal adjacent tissues obtained from these patients were also investigated. We
      found that COX-2 mRNA was detectable in these tissues. However, COX-2 mRNA and
      protein levels were lower in these tissues than in tumor specimens. In contrast,
      COX-2 mRNA and protein levels in normal oral mucosa obtained from healthy
      volunteers were very low or undetectable. The frequency of COX-2 overexpression
      was significantly higher in the N1-N3 group than in the N0 group. These results
      suggest that overexpression of COX-2 is linked with increased lymphatic invasion
      in hypopharyngeal carcinoma. Collectively, these results suggest that
      overexpression of COX-2 is a frequent phenomenon in hypopharyngeal carcinoma and
      may play a role in tumorigenesis of this cancer.

PMID- 11823980
TI  - Prognostic value of immunohistochemical expressions of p53, HER-2/neu, and bcl-2
      in stage I non-small-cell lung cancer.
AB  - The outcomes of patients with stage I non-small-cell lung cancer (NSCLC) vary
      greatly, with a 5-year survival rate of approximately 60%. This study evaluated a
      number of molecular markers that may aid in predicting prognosis in stage I NSCLC
      after surgical resection. Immunohistochemical (IHC) staining of p53, HER-2/neu,
      bcl-2 proteins was performed on paraffin-embedded sections from 85 stage I NSCLC
      patients who underwent surgery and were followed up for 32 to 44 (median, 39.0;
      mean, 37.1) months postoperatively. Differences in survival rates were evaluated
      by log rank test. The prevalence of p53, HER-2/neu, and bcl-2 expression in stage
      I NSCLC is 59%, 29%, and 46%, respectively. HER-2/neu expression is seen more
      frequently in adenocarcinomas, and bcl-2 is seen more frequently in squamous
      carcinomas. p53 and HER-2/neu expression in stage I NSCLC is associated with
      significantly short survival. Patients whose tumors were both p53 and HER-2/neu
      positive had the worst outcome, with a survival rate of only 20%, compared with
      80% in those whose tumors were both p53 and HER-2/neu negative (P = .0003). The
      survival rates were 54% in patients who were p53 positive but HER-2/neu negative
      and 50% in those who were in p53 negative, HER-2/neu positive. The differences
      among these 4 groups were statistically significant (P =.001). Bcl-2 does not
      seem to be a prognostic factor for survival. Multivariate analysis showed that
      overexpression of p53 and HER-2/neu, presence of angiolymphatic invasion, and
      tumor size > 3.0 cm were independent factors predicting poor survival. p53 and
      HER-2/neu by IHC staining appear to be valuable prognostic markers in stage I
      NSCLC patients after surgery. The worst outcome was seen in patients who
      expressed both p53 and HER-2/neu, suggesting that these patients might benefit
      from additional adjuvant therapy.

PMID- 11823981
TI  - Validity and reproducibility of histologic diagnosis and grading for adult soft
      tissue sarcomas.
AB  - Soft-tissue sarcomas in adults show great variations in histologic type and
      grade. A valid and reproducible prognostication system is needed to select
      patients with soft-tissue sarcomas who could benefit from adjuvant chemotherapy.
      This study was conducted to assess the validity and reproducibility of diagnosis
      of the histologic type, MIB-1 grade, and mitosis grade, as well as of the 3
      components of these grading systems. MIB-1 grade is a recently proposed grading
      system for predicting the prognosis of patients with adult soft-tissue sarcomas
      on the basis of 3 criteria (tumor differentiation, necrosis, and MIB-1 score) and
      replaces the mitotic count in the French system with MIB-1 immunohistochemical
      staining. Four surgical pathologists from 4 institutions who had experience in
      diagnostic soft-tissue tumor pathology reviewed 130 cases of soft-tissue sarcoma
      and independently determined histologic type and grade. The validity of
      histologic diagnosis was measured by sensitivity and specificity, and that of
      grading was measured by kappa statistics and percentage agreement with the
      diagnosis of the expert panel at the National Cancer Center, which was defined as
      a gold standard. Interobserver reproducibility was measured by kappa and by
      percentage agreement between the diagnoses of the 4 pathologists. The validity of
      the diagnosis of histologic type was high for synovial sarcoma, small round-cell
      sarcoma, and liposarcoma (sensitivity 89% to 100%; specificity, 98% to 100%) but
      low for malignant fibrous histiocytoma (MFH) and spindle-cell sarcoma (73% to
      75%; 93% to 95%). For the grading, the validity of the MIB-1 grade was
      substantial (kappa = 0.68; agreement, 79%) and higher than that of the mitosis
      grade (0.54; 69%). The most valid component was tumor differentiation (kappa =
      0.79), followed by tumor necrosis (0.66), MIB-1 score (0.59), and mitotic score
      (0.37). Interobserver reproducibility of histologic diagnosis was high for small
      round-cell sarcoma, synovial sarcoma, and liposarcoma (kappa = 0.92, 0.90, 0.87;
      percentage agreement = 99%, 97%, 96%, respectively); for grading, reproducibility
      was highest for tumor differentiation (0.78; 87%) and second highest for MIB-1
      grade (0.68; 79%). We conclude that diagnosis of the type of soft-tissue sarcoma
      for synovial sarcoma, small round-cell sarcoma, and liposarcoma and the MIB-1
      grading system based on tumor differentiation are highly valid and reproducible
      among Japanese pathologists who are familiar with the grading system, whereas re
      evaluation of histologic criteria is essential for other histologic types such as
      MFH and spindle-cell sarcoma.

PMID- 11823982
TI  - Central nervous system aspergillosis: a 20-year retrospective series.
AB  - Over the past 20 years at my institution, 71 patients with invasive necrotizing
      aspergillosis have been encountered; 42 have shown central nervous system (CNS)
      involvement by autopsy (40) or surgical biopsy (2). Most non-CNS aspergillosis
      patients had invasive disease confined to the lung, and only 2 with dissemination
      to 3 or more organs did not have spread to the CNS. In addition to the expected
      post-transplantation and hematologic malignancy cases, other risk groups
      identified included those with chronic asthma and steroid use, acquired
      immunodeficiency syndrome, thermal burn, hepatic failure, and postoperative
      infection. Unusual cases manifested with basilar meningitis, myelitis, proptosis
      caused by sino-orbital disease, or epidural and subdural Aspergillus abscesses.
      The extent of gross neuropathologic disease ranged from subtle abscesses to
      massive hemorrhagic necrosis causing herniation and death. In addition to the
      expected hemorrhagic necrosis, extensive hemorrhage, focal purulent meningitis,
      and subtle bland infarctions were also seen. Distinctive microscopic findings
      encountered included 1 case with numerous meningeal granulomas and multinucleated
      giant cells and 4 cases showing the Splendore-Hoeppli phenomenon. During the same
      period, single cases of cerebritis caused by morphologically similar fungi
      (Pseudoallescheria boydii [Scedosporium apiospermum], Scedosporium inflatum,
      Chaetomium sp) were identified and were indistinguishable from CNS aspergillosis
      clinically and pathologically.

PMID- 11823983
TI  - Heme oxygenase-1 deficiency: the first autopsy case.
AB  - This article describes the first autopsy case of heme oxygenase (HO)-1
      deficiency. A 6-year-old boy who presented with growth retardation; anemia;
      leukocytosis; thrombocytosis; coagulation abnormality; elevated levels of
      haptoglobin, ferritin, and heme in serum; a low serum bilirubin concentration;
      and hyperlipidemia was diagnosed as HO-1 deficient by gene analysis several
      months before death. Autopsy showed amyloid deposits in the liver and adrenal
      glands and mesangioproliferative glomerular changes in kidneys, in addition to an
      irregular distribution of foamy macrophages with iron pigments. Fatty streaks and
      fibrous plaques were noted in the aorta. Compared with HO-1--targeted mice, the
      present case seems to more severely involve endothelial cells and the
      reticuloendothelial system, resulting in intravascular hemolysis, disseminated
      intravascular coagulation, and amyloidosis with a short survival. This contrasts
      to the predominant iron metabolic disorders of HO-1--targeted mice with a long
      survival.

PMID- 11823985
TI  - Epstein-Barr virus-associated smooth muscle tumors in ataxia-telangiectasia: a
      case report and review.
AB  - Chromosomal breakage syndromes, including ataxia-telangiectasia (AT), are
      autosomal recessive disorders in which DNA repair mechanisms are defective
      resulting in chromosomal instability. Affected individuals are at high risk for
      developing malignancy because of the widespread resulting cellular effects. One
      such effect, severe immunosuppression, can permit virally mediated neoplasms to
      manifest, similar to those seen in acquired immunodeficiency syndrome (AIDS),
      congenital immune deficiency syndromes, and posttransplant populations. Epstein
      Barr virus (EBV) is a common viral agent known to be associated with lymphoid,
      epithelial, and smooth muscle malignancies in such patients. Although smooth
      muscle tumors have been reported in patients with AT, their association with EBV
      has not been evaluated. We present a case of EBV-associated laryngeal
      leiomyosarcoma and jejunal cellular leiomyoma in a child with AT. This case
      suggests that the development of neoplasia in patients with chromosomal breakage
      syndromes may be related to the immunosuppressive consequences of these diseases,
      and searching for infectious causes (such as EBV) is important.

PMID- 11823984
TI  - Esophageal extraskeletal Ewing's sarcoma.
AB  - Extraskeletal Ewing's sarcoma is a rare tumor. The most common sites of
      occurrence are on the trunk, extremities, and retroperitoneum. This type of tumor
      is well characterized by recurrent chromosomal translocation such as t (11;22)
      (q24;q12) (EWSR1/FLI1) or t (21;22) (q22;q12) (EWSR1/ERG) and overexpression of
      MIC2/CD99 on tumor cell membrane. We describe the first reported case of an
      esophageal extraskeletal Ewing's sarcoma with confirmation from
      immunohistochemical and molecular diagnoses. A 56-year-old man developed a
      polypoid tumor located in the lower part of the esophagus. The tumor was composed
      of small-sized round cells showing prominent fibrillar cytoplasmic processes.
      Intracytoplasmic glycogen was detected in all the tumor cells. Immunoreactivity
      for MIC2/CD99 was positive on the membrane of all tumor cells. A reverse
      transcriptase-polymerase chain reaction followed by sequencing revealed an
      EWSR1/ERG chimeric transcript, which combined EWSR1 exon 10 with ERG exon 6. The
      present report added a new entity of esophageal small round cell tumor.

PMID- 11823986
TI  - Serum and IMPOX B-reactins: how valuable? A critical revisit.

PMID- 11823988
TI  - Medicare medical nutrition therapy: legislative process and product.
AB  - The new Medicare benefit, medical nutrition therapy (MNT), came into effect
      January 2002-the product of a lengthy legislative process. Over several years,
      evidence-based advocacy by groups such as the American Diabetic Association and
      the National Kidney Foundation led to a legislative product that was introduced
      and passed by Congress. More recently, the legislation entered an implementation
      process, including the most recent Coverage Determination phase. The definition
      of MNT and the scientific evidence supporting it are presented. Evidence-based
      nutrition now enters a new phase of implementation and additional analysis.

PMID- 11823989
TI  - The metabolic conversion of phenylalanine into tyrosine in the human kidney: does
      it have nutritional implications in renal patients?
AB  - Recent evidence provided by the in vivo measure of the activity of phenylalanine
      hydroxylase in humans indicates that the kidney plays a role greater than
      previously presumed in phenylalanine conversion to tyrosine, an amino acid which
      has been considered nonessential so far. Homeostasis of tyrosine pools is only
      partially restored by a reduced uptake of the same amino acid by splanchnic
      organs in the well-nourished noncatabolic patient with chronic renal failure.
      Tyrosine pools in uremia can also be restored by an increase in endogenous net
      protein catabolism, because it occurs during treatment with nonbiocompatible
      membranes or during acidosis. However, these are trade-offs that are associated
      with a progressive decrease in muscle mass. Based on these findings, one can
      argue that with progressively declining renal function and kidney metabolic
      activity, the nutritional requirements for tyrosine increase progressively. This
      mechanism could in part account for the increased protein requirements in
      dialysis-treated end-stage renal disease patients, as compared with predialysis
      patients.

PMID- 11823990
TI  - Food intake characteristics of hemodialysis patients as obtained by food
      frequency questionnaire.
AB  - OBJECTIVES: Food frequency questionnaires (FFQ) are frequently used in
      epidemiologic studies of nutrition and food intake. However, the use of FFQs in
      patients receiving maintenance dialysis has not been extensively studied. We
      hypothesize that FFQ is a useful tool to assess the food intake differences
      between patients receiving dialysis and patients not receiving dialysis. DESIGN:
      Matched exposed-unexposed study with case-controlled design. SETTING: Outpatient
      dialysis unit affiliated with a tertiary-care community medical center. PATIENTS:
      From a pool of 102 maintenance hemodialysis (MHD) outpatients in a community
      dialysis unit, 30 adult MHD outpatients (15 men, 15 women, aged 55.8 +/- 14.6
      years) were selected randomly as case subjects. They included 16 African
      Americans, 8 whites, 4 Hispanics, and 2 Asians. Eleven MHD patients took the
      multivitamin, Nephrovite (R&D Laboratories, Marina del Rey, CA), regularly. From
      an archive of 1,610 nondialytic individuals with known FFQ data, 30 control
      subjects were selected randomly to match the age, race, and sex of the case
      subjects. INTERVENTION: We used Block's FFQ (version 98), an 8-page self
      administered questionnaire that has been widely used in epidemiologic studies. A
      group of trained research assistants supervised the FFQ administration and
      interviewed those patients who were not able to answer all of the questions
      without assistance. Student t test was used to compare group means in form of
      daily dietary intake, and conditional logistic regression was used to calculate
      odds ratios for predetermined dichotomizing cutoff levels. MAIN OUTCOME MEASURES:
      Food intake characteristics of MHD patients as compared with control patients not
      receiving dialysis. RESULTS: Statistically significant differences between MHD
      case subjects and nondialytic control subjects were observed between the amounts
      of daily intake for vitamin C (84 +/- 63 mg/d v 127 +/- 70 mg/d, P = .01),
      dietary fiber (12 +/- 6 g/d v 18 +/- 11 g/d, P = .02), potassium (2,024 +/- 1,088
      mg/d v 2,701 +/- 1,429 mg/d, P = .04), cryptoxanthin (56 +/- 88 microg/d v 140 +/
      118 microg/d, P = .003), and lycopene (2,052 +/- 2,234 microg/d v 4,524 +/-
      3,979 microg/d, P = .004). These data indicate that MHD patients had a
      significantly lower intake of vitamin C, dietary fibers, potassium, and 2 of the
      carotenoid compounds when compared with individuals not receiving dialysis.
      Moreover, the daily intake of vitamin B(6) was significantly higher in MHD
      patients probably because of the high pyridoxine content in Nephrovite. By using
      the conditional logistic regression analysis, the odds ratios for lower than
      predetermined cutoff levels in patients receiving dialysis were significant for
      vitamin C, potassium, and the 2 previously mentioned carotenoids (odds ratio
      between 3.50 and 7.50, P < .05). CONCLUSIONS: Patients receiving dialysis may
      consume significantly lower amounts of potassium, vitamin C, and dietary fibers
      as well as lower amounts of some carotenoids. The FFQ seems to be a useful tool
      to compare dietary intake of MHD patients with other groups, although it may
      underestimate the amount of daily protein and energy intake and, hence, may not
      be an accurate tool for individual assessment of food intake. More studies are
      required to evaluate the validity of the FFQ in dialysis patients. The lower
      vitamin C, fiber, and carotenoid intake of MHD patients may be atherogenic.
      Hence, the hypothesis is proposed that prescribed restrictions in potassium in
      MHD patients may lead to reduced fruit and vegetable intake, leaving meat and
      fats as the main source of calories. This may contribute to atherosclerosis and
      increased cardiovascular morbidity and mortality in these patients. This
      hypothesis needs to be evaluated in future studies.

PMID- 11823991
TI  - Vegetarian diet alternated with conventional low-protein diet for patients with
      chronic renal failure.
AB  - OBJECTIVES: A dietary management program, consisting of the alternation between a
      vegetarian low-protein diet (VD) and an animal-based conventional low-protein
      diet (CLPD), aims to increase foods choices and to improve compliance with
      dietary prescriptions, psychologic aspects, and the quality of life of renal
      patients. The present study investigates the subjective effects and the practical
      consequences of this dietary approach in patients with chronic renal failure.
      METHODS: Twenty patients (13 men, 7 women, 53 +/- 10 years) with chronic renal
      failure (creatinine clearance, <45 mL/min) were given the possibility to
      alternate (at their own convenience) the CLPD with the VD. After a follow-up
      period of 9 +/- 8 months, biochemistries were drawn and a questionnaire was
      mailed to asses the patients' subjective remarks about the proposed dietary
      management. RESULTS: Most of the patients (90%) favorably accepted this dietary
      schedule because it provided more variety, it was less repetitive, and it was
      more suitable for those leading an active life. In many cases, patients reported
      that their quality of life and some psychologic problems were improved, as well
      as the palatability of the diet. On this dietary regimen, monthly demands of
      starch-made foods can be reduced and, hence, the social and/or individual costs.
      These features contributed to better compliance with dietary prescriptions.
      Nutritional parameters did not change significantly, and a decrease in total and
      low-density lipoprotein cholesterol levels were observed. CONCLUSIONS: Our
      observations suggest that alternating between an animal-based CLPD and a
      vegetable-based VD can provide a useful dietary management for renal patients,
      giving them more chances for long-lasting dietary compliance.

PMID- 11823992
TI  - Iron and zinc status of patients with chronic renal failure who are not on
      dialysis.
AB  - OBJECTIVE: The purpose of this study was to assess the zinc and iron status in
      patients with chronic renal failure (CRF) who were not receiving dialysis.
      DESIGN: Cross-sectional study. SETTING: Outclinic patients of the Nephrology
      Division at Federal University of Sao Paulo. PATIENTS: This study was performed
      on 29 stable patients with CRF who were not receiving dialysis. MAIN OUTCOME
      MEASURE: The parameters for determining iron and zinc status were transferrin
      saturation, zinc protoporphyrin, serum ferritin, hematocrit, serum iron, total
      iron binding capacity, erythrocyte, and plasma zinc levels (measured by atomic
      absorption spectrophotometry). RESULTS: The serum ferritin level was reduced to
      85.5 +/- 67.1 ng/mL and the zinc protoporphyrin level was high (68 +/- 32.9
      micromol/mol heme), serum transferrin saturation was 19.9% +/- 7.85%, mean serum
      iron level was 66.6 +/- 26.3 microg/dL, and mean total iron binding capacity was
      336 +/- 45.7 microg/dL. Absolute iron deficiency was found in 34.5% of the
      patients. Zinc level in erythrocytes was high (50.0 +/- 7.2 microg/g hemoglobin),
      whereas plasma zinc was at a borderline level (74 +/- 17.7 microg/dL) when
      compared with normal values. There were significant correlations among plasma
      zinc and serum iron and transferrin saturation, zinc erythrocyte, and parameters
      of iron. CONCLUSION: These results show that absolute iron deficiency can occur
      in patients who are not receiving dialysis and that there is an abnormal
      distribution of zinc levels in these patients. Moreover, a possible relationship
      between iron deficiency and zinc distribution was observed.

PMID- 11823993
TI  - Dialysis and nutrition practices in Korean hemodialysis centers.
AB  - OBJECTIVE: Survey the dialysis practices and nutritional status-related patient
      characteristics. DESIGN: Cross-sectional survey. SETTING: Twenty-eight randomly
      selected Korean hemodialysis facilities. METHODS: Medical record review of 140
      randomly selected patients in 28 Korean dialysis facilities. The Student t test
      and chi-square tests were used to compare facility types and locations. RESULTS:
      The mean number of dialysis treatments per week was 2.7 +/- 0.4. Mean dialysis
      treatment length was 253 +/- 27.5 minutes. Rural dialysis centers reported fewer
      treatments per week and shorter dialysis treatment times than did urban centers
      but, otherwise, there were few differences by either location (urban v rural) or
      by facility type (hospital affiliated v freestanding facility). The mean age of
      the patients surveyed by record review was 51 +/- 14 years, and 59% of the
      patients were men. The primary causes of end-stage renal disease were chronic
      glomerulonephritis, hypertension, and diabetes. Average vintage of dialysis was
      53 +/- 46 months. Adequacy of dialysis was usually assessed by using clinical
      judgment; urea kinetic modeling and urea reduction ratios were used less
      frequently. Patients' mean body mass index was 20.7 +/- 2.3, which was at the
      lower end of the healthy range of 18.5 to 25, and most (93%) of their weights had
      been stable over the previous 6 months. Their mean serum albumin level was 4.0 +/
      0.4 g/dL. Forty-two percent of patients used iron supplements and 68% of them
      received erythropoietin treatment. However, their mean hematocrit levels were
      only 25.9% +/- 4.2%, suggesting that iron supplements were underused or
      erythropoietin doses were lower than optimal. Virtually all patients (94%) had
      received initial diet instruction but few (6%) received follow-up nutrition
      counseling. CONCLUSION: Greater attention to dialysis adequacy, hematocrit
      levels, nutrition assessment, weight monitoring, and diet therapy are
      recommended.

PMID- 11823994
TI  - Clinical and dietary indicators associated with uremic status in hospitalized
      dialysis patients.
AB  - OBJECTIVE: The objective of this study was to determine whether any differences
      existed between specific admission variables and uremic status in patients with
      chronic renal failure receiving dialysis. DESIGN AND SETTING: This was a
      prospective, observational study conducted at BryanLGH Medical Center East Campus
      in Lincoln, Nebraska. PATIENTS: The subjects were hemodialysis and peritoneal
      dialysis patients admitted to an acute care facility, who met the following
      inclusion criteria: (1) they had a primary or secondary underlying diagnosis of
      chronic renal failure, and (2) they were not receiving parenteral or enteral tube
      feeding nutritional support on admission. INTERVENTION: The patients were
      separated into 2 groups by their blood urea nitrogen (BUN) concentrations. Group
      1 had a BUN concentration less than 50 and group 2 had a BUN concentration
      greater than or equal to 50. Admission data (age, sex, percentage of ideal body
      weight, reported retrospective weight loss over time, type of dialysis,
      gastrointestinal history, BUN and creatinine concentrations, and dietary
      prescription) were collected from patient medical records. Two-day kilocalorie
      and protein counts were conducted on the patients within 24 hours of admission to
      the acute care facility. Chi-square and 1-way analysis of variance were performed
      to compare the groups. RESULTS: The total number of participants in the study was
      42, with 21 in each BUN group. The mean age was 60 years, and the dietary intake
      was a mean of 10 kcal/kg and 0.4 g protein/kg. Only 14.3% and 7.1% of the
      patients met their kcal and protein needs, respectively. The mean percentage
      ideal body weight was 125 and the mean reported weight loss per week was 2.6
      pounds. Gastrointestinal symptoms, specifically nausea and a kilocalorie
      restricted diet prescription, were significantly different between the 2 groups.
      Patients in group 2 were more likely to have gastrointestinal symptoms overall (P
      < .05) specifically, nausea (P <.05). Group 1 patients were also more frequently
      placed on a kilocalorie-restricted diet (P < .05) than patients in group 2.
      CONCLUSIONS: A BUN concentration between 50 and 110 has been shown to be
      associated with a lower risk of death and a better nutritional status. These
      findings indicate symptoms commonly associated with uremia, such as nausea, may
      be associated with the dialysis patient's nutritional status when BUN
      concentrations are greater than 50. These dialysis patients were not receiving
      sufficient kilocalories and protein on admission into the hospital, and this can
      affect their nutritional and, eventually, survival status.

PMID- 11823995
TI  - Intradialytic parenteral nutrition in malnourished children treated with
      hemodialysis.
AB  - OBJECTIVE: To examine the feasibility and effectiveness of intradialytic
      parenteral nutrition (IDPN) in children on hemodialysis. DESIGN: Prospective
      experimental study with a single intervention group. SETTING: A pediatric
      hemodialysis unit. SUBJECTS: Four malnourished children on hemodialysis (3 girls
      and 1 boy) 4 to 18 years of age were studied during a period of 1 year.
      INTERVENTION: IDPN, which is composed of amino acids (8.5% solution), glucose (as
      10% to 15% dextrose), and 20% fat emulsion, was administered at every dialysis
      session (3 times a week, during 4 hours each time) for 7 to 12 weeks. MAIN
      OUTCOME MEASURE: Oral caloric intake (evaluated by using a 3-day diet history),
      dry weight (weight after dialysis), body mass index, percent ideal body weight,
      total lymphocyte count, and serum levels of albumin before, immediately after
      cessation of IDPN, and 3 months after cessation of IDPN. RESULTS: Oral caloric
      intake increased markedly after IDPN administration, from 5 to 63 kcal/kg/d
      (mean, 33 kcal/kg/d) before IDPN administration to 35 to 177 kcal/kg/d (mean, 86
      kcal/kg/d) at the time of cessation. Weight did not change during the treatment
      period but it did increase from 9.5 to 36.4 kg (mean, 25 kg) to 11 to 39 kg
      (mean, 26.7 kg) 3 months later. Percent ideal body weight increased from 73% to
      88% (mean, 78.5%) to 79% to 90% (mean, 85.1%), and body mass index increased from
      12.2 to 15 kg/m(2) (mean, 13.5 kg/m(2)) to 13.4 to 15.5 kg/m(2) (mean, 14.6
      kg/m(2)). Total lymphocyte count increased from 538 to 2,041 cells/mm(3) (mean,
      1,403 cells/mm(3)) to 724 to 2,884 cells/mm(3) (mean, 2,066 cells/mm(3)). Plasma
      levels of albumin increased in 1 patient but remained unchanged in others.
      CONCLUSION: Short-term IDPN treatment may serve as a safe and effective
      nutritional intervention in malnourished children on hemodialysis.

PMID- 11823996
TI  - Patient education; foods high in magnesium.

PMID- 11823998
TI  - Results of the RAPID 1 and RAPID 2 thrombolytic trials in acute myocardial
      infarction.
AB  - Two angiographic trials, RAPID 1 in 606 patients and RAPID 2 in 324 patients,
      assessed angiographic patency after acute myocardial infarction following
      treatment with reteplase and alteplase. RAPID 1 evaluated three bolus regimens of
      reteplase in comparison with a 3 h infusion of alteplase. RAPID 2 compared the 10
      MU + 10 MU double bolus regimen of reteplase with the accelerated regimen (90 min
      infusion) of alteplase. The results of these studies showed that reteplase opened
      more arteries more quickly than did alteplase. Angiography at both 60 and 90 min
      showed a higher rate of patency and greater TIMI (Thrombolysis in Myocardial
      Infarction perfusion grade) 3 flow rates with reteplase than with alteplase. In
      RAPID 1, at 90 min, TIMI 3 flow rates were 63% for reteplase compared to 49% for
      alteplase (P < 0.05), and in RAPID 2, TIMI 3 flow was 60% vs 45%, respectively,
      (P < 0.05). Reteplase was convenient and simple to administer, and there were no
      unexpected complications. Fewer interventional procedures were performed after
      therapy with reteplase than with alteplase, primarily because coronary
      angioplasty was required less frequently following acute angiography in patients
      receiving reteplase. The angiographic profile for reteplase demonstrated in these
      two trials suggests that this new thrombolytic drug has potential advantages over
      alteplase: notably, its use can result in earlier and more complete coronary
      patency. The clinical significance of this finding must be determined in larger
      clinical trials.

PMID- 11823999
TI  - The rationale for thrombolytic therapy.
AB  - Substantial progress has been made toward understanding the pathophysiological
      processes that lead to acute myocardial infarction. Research has shown that the
      mechanism of infarction is the rupture of an atherosclerotic plaque with a
      subsequent thrombogenic response from exposed subendothelial tissue, leading to
      additional or complete obstruction of the vessel. Myocardial cell death then
      proceeds in a wavefront fashion from the subendocardium to the epicardium. Time
      to myocardial reperfusion and the extent of collateral flow are the primary
      determinants of final infarct area. This knowledge led to the development of
      therapeutic strategies to achieve early and sustained reperfusion of the infarct
      related vessel, the presumption being that this would result in increased
      myocardial salvage and better residual left ventricular function in addition to
      reductions in infarct expansion and electrical instability. The results of
      several large thrombolytic trials have supported this model, showing that
      patients who receive thrombolytic therapy derive a constant relative survival
      benefit when compared with control patients. The largest comparative thrombolytic
      trial to date has shown that therapies that result in early, more complete
      reperfusion are indeed associated with lower mortality; however, these therapies
      may be associated with higher rate of complications such as intracranial
      haemorrhage and reocclusion. Future evaluations must include assessment of the
      benefits relative to the risks of newer, more potent thrombolytic regimens.

PMID- 11824000
TI  - Thrombolytic therapy in Europe: current status.
AB  - Thrombolytic therapy is a practical, effective approach to the management of
      acute myocardial infarction that is widely used in Europe today. Early European
      trials demonstrated a clear reduction in mortality in patients who received
      thrombolytic therapy compared with those given conventional treatment. The
      findings of experimental studies suggest that early reperfusion of the infarct
      related artery reduces myocardial damage, which results in the preservation of
      left ventricular function and, in turn, may improve survival. Although tissue
      plasminogen activator (t-PA) has been shown to produce more rapid and complete
      reperfusion than streptokinase, two large-scale clinical trials in which t-PA was
      given as a standard 3- or 4-h infusion provided no evidence of a survival
      advantage with this agent. However, the accelerated t-PA regimen used in the
      Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded
      Coronary Arteries (GUSTO) study was associated with a lower mortality than
      streptokinase or a combination of t-PA and streptokinase, thus lending support to
      the 'open artery' theory. Two recent studies conducted in Europe, the Grampian
      Region Early Anistreplase Trial (GREAT) and the European Myocardial Infarction
      Project (EMIP), have demonstrated the feasibility, safety, and efficacy of early
      thrombolytic therapy before admission to hospital. In GREAT, anistreplase (APSAC)
      was administered at home by general practitioners. In EMIP, this same agent was
      given by emergency medical personnel. In both studies, pre-hospital
      administration reduced the time between the onset of symptoms and initiation of
      thrombolysis and was associated with a lower mortality rate. Recent data from the
      European Cooperative Group Study show that the benefits of thrombolytic therapy
      are maintained for up to 5 years. Research continues in an effort to develop
      safer and more effective thrombolytic agents. Educational efforts to familiarize
      the public with the symptoms of myocardial infarction and the development of more
      rapid, efficient emergency response systems may also improve the outcome of
      thrombolytic therapy by shortening the time between symptom onset and
      thrombolytic drug administration.

PMID- 11824001
TI  - Mega-trials and equivalence trials: experience from the INJECT study.
AB  - As treatments for acute myocardial infarction have grown in number and
      effectiveness, the post-infarction mortality rate has fallen, and new therapies
      can provide only a small additional advantage in extending survival. To prove
      such an advantage of a new drug over its predecessors in the same drug class
      requires a trial of at least 20,000 patients. Proving 'equivalence' rather than
      superiority requires only 6000 patients. The INJECT trial was designed with the
      modest goal of determining whether the novel agent reteplase (recombinant
      plasminogen activator) has an effect on mortality equivalent to that of
      streptokinase. Between August 1993 and September 1994, 6010 patients were
      randomized to receive either reteplase (n = 3004) or streptokinase (n = 3006).
      Both treatment groups had similar rates of bleeding events, extension or
      recurrence of myocardial infarction, and in-hospital stroke followed by 6 months
      of disability. Reteplase recipients had a lower incidence of cardiac events in
      hospital and fewer allergic reactions. Although the number of diagnosed
      haemorrhagic strokes was higher in reteplase recipients, more patients receiving
      streptokinase had strokes of uncertain aetiology. At 35 days, the mortality rate
      associated with reteplase use was approximately 0.5% lower than that associated
      with streptokinase administration, and the upper limit of the 90% confidence
      interval for the difference between these rates was a superiority of
      streptokinase of 0.73%. Because the INJECT trial provided a probability of 0.95
      that the mortality rate associated with reteplase use would be either lower than
      that with streptokinase administration or at most 0.73% worse, reteplase and
      streptokinase were proved equivalent according to the trial definition and
      limits.

PMID- 11824002
TI  - Clinical markers of thrombolytic success.
AB  - Although a number of markers of successful coronary thrombolysis have been
      proposed, only a few of these have the two necessary features of a clinically
      useful marker: (1) widespread early availability and (2) good predictive value.
      The reduction in ST-segment elevation on the standard 12 lead electrocardiogram 1
      4 h after initiation of thrombolysis may be the simplest and most useful clinical
      'tool' to gauge the effectiveness of thrombolytic therapy. The predictive value
      of this single marker might be further improved by combining it with assessment
      of the rate of increase of serum myoglobin and of troponin T, provided these
      determinations were rapidly available.

PMID- 11824003
TI  - Early myocardial reperfusion: an assessment of current strategies in acute
      myocardial infarction.
AB  - Early, complete, and sustained myocardial reperfusion is the principal goal of
      thrombolytic therapy. Unfortunately, the majority of patients treated today
      experience substantial delay before the initiation of thrombolytic therapy and,
      once treated, demonstrate suboptimal results of coronary thrombolysis. This is
      attributable, in part, to the underlying thrombus, which is platelet rich and
      resistant to plasminogen activators, and to the pro-thrombotic effects of
      fibrinolytics, which have no favourable effect on thrombin. Future therapeutic
      interventions will focus on improved reperfusion. Pharmacological strategies
      including novel plasminogen activators, direct thrombin inhibitors, and platelet
      glycoprotein IIb/IIIa inhibitors have all generated encouraging early clinical
      trial data and await further study. Mechanical reperfusion therapy with primary
      balloon angioplasty is particularly effective; its use is associated with the
      establishment of more complete infarct vessel patency than are thrombolytics.
      Considerable potential for the improvement of current reperfusion-directed
      therapy exists.

PMID- 11824004
TI  - Thrombolysis and mechanical intervention following myocardial infarction.
AB  - In concept, mechanical interventions are attractive options for treating acute
      myocardial infarction with or without preceding thrombolysis: rapid reperfusion
      of the infarct-related artery can be achieved in the vast majority of cases, and
      the underlying coronary lesion is treated at the same time. Various strategies
      have been extensively investigated. When performed in specialized centres, direct
      percutaneous transluminal coronary angioplasty (PTCA) without prior thrombolysis
      appears to improve the outcome more than conventional thrombolysis. Whether this
      also holds true for the diverse range of hospitals remains unknown. Routine PTCA
      after thrombolysis did not show any benefit over thrombolysis alone. Rescue PTCA
      after failed thrombolysis is probably beneficial. Currently, only limited
      experience exists with other mechanical interventions, including intra-aortic
      balloon pumping, thrombectomy with special new devices, or stent insertion, which
      need further investigation before they can be recommended for routine use in
      acute myocardial infarction.

PMID- 11824005
TI  - The future of thrombolysis in the treatment of acute myocardial infarction.
AB  - The ability of thrombolytic therapy to lower mortality in patients with acute
      myocardial infarction was first demonstrated in 1986 by the Gruppo Italiano per
      lo Studio della Streptochinasi nell'Infarto Miocardico. In the ensuing 10 years,
      large efforts have been undertaken to develop more effective and safer
      thrombolytic agents. In addition, the value of adjunctive agents influencing
      thrombotic and thrombolytic processes was demonstrated, and newer agents are
      under active investigation. This review focuses on theoretical and practical
      aspects of optimizing thrombolytic therapy and on genetically engineered third
      generation plasminogen activators. Optimized thrombolytic therapy may make this
      form of therapy available to patients who are currently considered ineligible,
      and it will lead to earlier, more complete reperfusion of infarct-related
      coronary arteries. The benefits and risks of optimized thrombolytic regimens
      relative to those of mechanical reperfusion strategies will require constant
      reassessment while both forms of treatment develop.

PMID- 11824006
TI  - Perspectives gained from large-scale thrombolytic comparative trials.
AB  - Four thrombolytic comparative trials without a placebo arm have each been
      conducted in populations of more than 1000 patients: GISSI-2 International, ISIS
      3, GUSTO, and INJECT. The treatment strategy associated with use of intravenous
      heparin and the accelerated regimen of tissue plasminogen activator (t-PA)
      accounts for the differences between the results of GUSTO and those of the
      earlier studies of GISSI-2 International and ISIS-3. Using analysis of predefined
      parameters, it is possible to identify those subsets of patients most likely to
      benefit from accelerated administration of t-PA. A useful profile of patients at
      risk for intracranial haemorrhage has also been derived; this profile enhances
      efficient, sensible, individualized decision making. Results from the
      angiographic substudy of GUSTO highlight the fundamental importance of early
      coronary artery patency as a determinant of improved left ventricular function
      and survival and reaffirm the usefulness of left ventricular function as a
      surrogate measure for assessing the efficacy of novel reperfusion strategies. In
      addition, the opportunity to evaluate international differences in practice
      patterns, coupled with measures of quality of life and return to work, has given
      new insight into the importance of these issues in the care of patients with
      acute myocardial infarction. Future investigation must address the challenge of
      optimal use of resources in assessing novel therapies. Strategies include
      logistic modelling, surrogate end-points, sample enrichment with high-risk
      subsets, blended end-points, and uneven randomization.

PMID- 11824009
TI  - Health in Barbados in the 20th century.
AB  - At the beginning of the 20th century, Barbados was described as the most
      unhealthy place in the British Empire; at the end of the century, it is
      considered amongst the healthiest of developing countries. At the start of the
      century the statistics were harsh; for example, there was an infant mortality
      rate of 400 per 1000 live births. It is now between 10 and 15 per 1000 live
      births. In the last two-thirds of the century, there was a series of ongoing
      revolutions in Education, Public Health and Hospital Services that affected the
      health status favourably. The revolution in education was enhanced by the
      provision of University education starting with Medicine at Mona, Jamaica.
      Training of doctors expanded to Barbados in 1967 and has been an essential
      ingredient in the medical care revolution of the last third of the century. In
      1953, the first Public Health Centre was opened and Barbados can now boast the
      most modern public health and primary care facilities. However, modern lifestyles
      are associated with an epidemic of obesity, diabetes mellitus and hypertension.
      HIV/AIDS has emerged as a major problem. Health in the 21st century will need to
      look at lifestyles--the effects of the internal combustion engine, the
      availability of tools of violence, the lure of 'illegal drugs', personal
      relationships and gender as well as the driving forces behind the associated
      lifestyles.

PMID- 11824010
TI  - Health trends in Jamaica. Significant progress and a vision for the 21st century.
AB  - Health trends in Jamaica have improved considerably during the past century. Life
      expectancy at birth increased from 38 years in 1900 to 72 years in 2000. The
      crude death and infant mortality rates declined significantly from 35.7 and 174.3
      deaths to 5.1 and 24.4 deaths, respectively, in the same period. The seven
      leading causes of death in 1945 were infectious diseases while the main causes of
      mortality and morbidity are now the chronic non-communicable lifestyle diseases,
      and injuries. Over the past few decades, considerable progress has been made in
      controlling vaccine preventable diseases and eliminating poliomyelitis and
      measles. Rates of infectious syphilis, congenital syphilis and gonorrhoea have
      declined significantly in recent years although chlamydia and herpes are common
      and the HIV/AIDS epidemic is a growing concern. Over the past few decades health
      expenditure has grown more rapidly in the private health sector than in the
      public health sector although services in the public sector are provided at
      significantly lower cost. Jamaica provides good health at low cost. However, more
      funds are needed to support the public health system. The current health reform
      process needs to be informed by a better understanding of the factors that have
      contributed to Jamaica's achievements in health and needs a clear health focus.
      The Ministry of Health has articulated a vision of health for the 21st century
      that requires a significant reorientation of health staff as well as empowering
      people to take responsibility for adopting healthy lifestyles.

PMID- 11824011
TI  - Research, health policies and health care in the Caribbean. The role of the
      University of the West Indies.
AB  - The University of the West Indies has had a major impact on the provision of
      health care and the health of Caribbean nations over the last 50 years, through
      undergraduate, postgraduate and continuing medical education, research, outreach
      and public service. These roles are fully accepted, and the Faculties of Medical
      Sciences and School of Clinical Medicine and Research have provided most of the
      doctors now serving the English-speaking Caribbean, including academic leaders
      and chief medical officers. The design of a curriculum to produce doctors
      "designed" for the region has been a well-articulated goal, and the need to carry
      out relevant and essential national health research is now accepted. But the
      broader roles of ensuring translation of research into policy and practice, and
      developing effective ways of promoting on-going continuing training and behaviour
      change are far from understood or seriously attempted. Communication of research
      findings and evidence-based practice is crucial. The West Indian Medical Journal
      clearly has a valuable role to play here and this requires expansion and support.
      But a multi-faceted approach to communicating research findings and translating
      evidence into policy, planning and care is necessary. One possible approach would
      be a University Unit of Health Policy Research and Development.

PMID- 11824012
TI  - Chronic diseases--facing a public health challenge.
AB  - Middle income countries like those in the Caribbean can feel proud of their
      achievements in health care. There has been a dramatic fall-off in infant
      mortality and crude mortality rates along with significant improvements in life
      expectancy at birth. However, these countries now find themselves grappling with
      the burden of chronic non-communicable diseases such as heart disease, stroke,
      hypertension, diabetes mellitus and cancer. There are good data to support the
      view that some of these diseases, in particular diabetes mellitus, have assumed
      epidemic proportions and there is concern that this fact may have been missed by
      many because of the surreptitious onset, as is the nature of the chronic
      diseases. The impact of this epidemic may have suffered because of the higher
      profile of more topical issues like HIV/AIDS even though the former makes a
      larger contribution to morbidity and mortality statistics. It is now obvious that
      despite the impact of other factors, lifestyle changes are the major contributors
      to the epidemic. In populations of similar genetic stock, living in significantly
      different socio-economic circumstances, the impact of increased dietary salt,
      increasing obesity and decreased physical activity on the prevalence of
      hypertension, diabetes mellitus and lipid disorders is unequivocal. Data from the
      developed world, which has already been through this epidemic of chronic
      diseases, have shown that increasing technological advances in medical care is an
      inefficient way to respond to the situation. A multi-sectoral approach is
      required to tackle this epidemic, including the provision of incentives for
      healthy eating and widespread opportunities for increased exercise and other
      physical activities. Continued research into the evolution of the epidemic,
      including reliable estimates via surveillance methods is a necessary component of
      our response. The problems and the solutions are not only the responsibilities of
      the health officials but must involve education, agriculture and other sectors of
      the economy.

PMID- 11824013
TI  - Laboratory services--development and future directions.

PMID- 11824014
TI  - The development of a community-based comprehensive mental health service delivery
      system for the Cayman Islands (1989-2001).
AB  - This paper reviews the development of mental health services in the Cayman
      Islands throughout a twelve-year period (1989 to 2001). I was appointed the
      resident consultant psychiatrist to the islands in 1989, after which time a
      consultative process between the Ministry of Health, Senior Management of the
      George Town Hospital and myself allowed the development and establishment of a
      comprehensive community-based mental health service delivery system (MHSDS),
      specifically designed to suit the needs of the Cayman Islands. The components of
      the MHSDS and their evolution in the absence of adequate facilities are reported.
      The framework for the service is outlined, and the concerns and objectives of the
      MHSDS are discussed, along with short-term and long-term goals.

PMID- 11824015
TI  - Golden jubilee.

PMID- 11824016
TI  - The teaching facility at the Eric Williams Medical Sciences Complex. An
      additional rising star from the west.
AB  - The teaching facility at the Eric Williams Medical Sciences Complex was designed
      to provide a comprehensive structural environment for a multidisciplinary Faculty
      whose teaching methodology utilized an integrated Problem-based Learning
      approach. Though the Faculty is over 11 years old, the full realization of the
      vision has not become a reality and the next 10 years will be devoted to
      fulfilling the dream.

PMID- 11824017
TI  - Medical library--then and now.
AB  - The paper traces the Medical Library's growth, development and its relationship
      with the Faculty of Medical Sciences (FMS), researchers and other users pursuing
      their teaching, research and patient care. The information is analyzed,
      synthesized and organized from the Annual Reports of the Vice Chancellor,
      Principal, Libraries, various Departments in the Faculty of Medical Sciences,
      Office of Planning, Institutional Research, and the Web Pages of University of
      the West Indies, Mona, Jamaica.

PMID- 11824018
TI  - Fifty years of clinical examinations at the University of the West Indies.
AB  - The University of the West Indies was founded at Mona, Jamaica, in 1948. After
      fifty-two years, the format of the final Bachelor of Medicine clinical
      examination in Medicine and Therapeutics has been radically revised. The change
      from the traditional to an evidence-based, objective structured clinical
      examination (OSCE) was undertaken in November/December 2000. Assessment drives
      learning and both the methods chosen for assessment and the manner in which they
      are applied determine how students learn. The philosophical underpinnings of the
      change in format are discussed in this paper.

PMID- 11824019
TI  - Every physician is a scientist.

PMID- 11824020
TI  - The development of primary health care in Jamaica.
AB  - The development of primary health care in Jamaica is explored, tracing its early
      roots to the abolition of the slave trade, the collapse of estate-based services
      after emancipation and the subsequent establishment of the Island Medical
      Services in 1875. Most development in the health sector occurred after World War
      I in response to the high infectious disease mortality rates. The Rockefeller
      Foundation was asked to assist with the control of hookworm, tuberculosis,
      malaria and yaws. Its recommendations led to the growth of public health
      programmes (e.g. environmental health, public health nursing, community
      midwifery) alongside community-based curative services run by hospitals. The most
      significant period of development occurred in the 1970s when the various vertical
      programmes were integrated into the current primary care system. Jamaica was
      integral in the development of the World Health Organization's Alma Ata
      Declaration on Primary Health Care, tabling the "Jamaican Perspective on Primary
      Health Care" which set out its goal that all citizens should be within 10 miles
      walking distance of a primary health care facility. At the close of the twentieth
      century, the health reform process led to the development of regional health
      authorities aimed at integrating the management of primary and secondary care
      under four Regional Boards of Health. This has led to a change in the role of the
      central Ministry of Health to one of policy-making, health promotion, setting
      standards, monitoring and evaluation of the quality of health care.

PMID- 11824021
TI  - Kenneth Harrison Uttley (1901-1972). Historian to the diseases of Antigua,
      British West Indies.
AB  - Dr Kenneth Harrison Uttley (1901-1972) served as the Chief Medical Officer in
      Antigua, British West Indies, from 1955 until 1966. During this time, Dr. Uttley
      personally reviewed and tabulated an island-wide governmental demographic
      database of all births, deaths and causes of death during the preceding 100
      years. This database was the result of a Compulsory Birth and Death Registration
      Ordinance enacted as one of several Colonial Poor Laws in 1856. His efforts
      resulted in the publication of a total of 30 papers in American and British
      medical journals. Many of these papers reviewed historical demographic trends in
      births, fertility rates, neonatal deaths, infant mortality and early childhood
      mortality rates. Others focussed on the historical epidemiology of specific
      diseases such as neonatal tetanus, leprosy, tuberculosis and malaria. This is the
      first complete bibliographical account of Uttley's contributions to the history
      of diseases in the West Indies in general and Antigua in particular. Dr Uttley
      also served as an ordained priest in the Anglican Church and, upon retirement
      from the Colonial Medical Services, returned to England to serve as the Vicar of
      Purton, Oxfordshire.

PMID- 11824022
TI  - [Posterior pelvic exenteration in locoregional recurrence of rectal carcinoma-
      indications, technique and outcome].
AB  - Despite a potentially curative operation in over 70% of rectal carcinomas, local
      recurrence is observed in up to 55%. The most common location is at or around the
      anastomosis and the presacral region. Locoregional recurrence is--apart from
      distant metastases--the most important factor determining prognosis and survival.
      If an R0 resection can be performed, a 5-year survival rate of 20-30% can be
      achieved. Whether patients will benefit from a palliative operation is still a
      matter of debate. Morbidity is estimated to exceed 60% and perioperative
      mortality always below 10%. In this article, we review the indication,
      preoperative diagnostic and therapeutic procedures as well as results of the
      posterior pelvic exenteration with sacral resection. Taking all aspects into
      account, posterior pelvic exenteration seems to be justified due to the lack of
      alternatives and the potential benefit of palliative and curative resection. With
      respect to the effort in time, personnel, surgical expertise and logistics, this
      operation should be preferably performed in specialized and well-equipped medical
      institutions.

PMID- 11824023
TI  - [Strategy and technique in perineal impalement injuries].
AB  - Injuries of the anal sphincter and the pelvic floor are rare and have a large
      range of variations. This report is based upon 28 patients with perineal injuries
      treated in a 17-year period. Mortality depends on accompanying injuries. The
      degree of the injury determines the functional result. Proximal diversion and
      drainage represent the standard treatment for intra-abdominal rectal injuries. In
      extraperitoneal rectal injuries diversion, presacral drainage and distal rectal
      washout is recommended. Loss of continence is the most severe complication of
      injuries of the anal sphincter. The best results are obtained by primary repair.

PMID- 11824024
TI  - [Orthopedic/visceral surgery cooperation in pelvic tumors].
AB  - Co-operation between orthopaedic surgeons and visceral surgeons is required in
      the treatment of malignant tumours of the pelvis when the rectum or the iliac
      vessels are infiltrated. Such infiltration can be expected in malignancies which
      originate in the sacrum. Most frequently, chordomas are found in this area, that
      should be resected with wide surgical margins even in advanced tumours to reduce
      the risk of local recurrence. When resecting the sacrum, the stability of the
      vertebral column and the pelvis is compromised only at levels above S2. After
      unilateral resection of the sacral nerve roots S2-S5, there are only minor
      impairments of the anal and bladder sphincter control. In the case of tumour
      infiltration of the rectum and simultaneous resection of the sacral nerve roots,
      abdominoperineal extirpation of the rectum is required even when a safe margin is
      left between the tumour and the anal sphincter. In different studies, the 5-year
      survival in patients with a malignancy of the sacrum varies between 52% and 84%.
      In view of the rarity of these tumours, treatment should be performed only at
      specialized centers where co-operation is ensured.

PMID- 11824025
TI  - [Surgical treatment of axillary hidradenitis suppurativa].
AB  - INTRODUCTION: Hidradenitis suppurativa is a chronic inflammatory disease of the
      cutis with furuncles, fistulas and abscesses, mostly located in the groin and
      axillary regions. A conservative treatment can not prevent a recurrence. PATIENTS
      AND METHODS: We report on 16 patients with axillary hidradenitis suppurativa. The
      inflammatory region was excised, followed by immediate coverage with a
      transposition flap according to Limberg. Postoperatively, all patients received
      antibiotic treatment. After 2 weeks, physiotherapy was begun. RESULTS: All wounds
      healed primarily. Functional and aesthetic results were very satisfactory.
      Movement of the shoulder showed no restrictions. There was no major complication.
      The recurrence rate was low. DISCUSSION: Only radical debridement prevents a
      recurrence. The therapy of choice is radical excision of the affected region and
      immediate coverage by a transposition flap. Open granulation or split-skin
      grafting are inferior compared with a primary closure by transposition flap.
      Using the Limberg flap the donor site can be closed primarily.

PMID- 11824026
TI  - [Postoperative nausea and vomiting (PONV). Clinical significance, basic
      principles, prevention and therapy].
AB  - INTRODUCTION: The incidence of postoperative nausea and vomiting (PONV) of in-
      and outpatient surgical patients is about 30% (range 2-45%). METHODS: Based on
      etiology, anatomy and physiology, this review article provides a critical
      evaluation of the present PONV literature with the aim of outlining current
      prophylaxis and treatment strategies. RESULTS: PONV is often associated with
      postoperative pain and its treatment. Patients are often more compromised by PONV
      than by postoperative pain. Surveys demonstrate that 78% of the surgeons consider
      PONV to be a relevant problem in clinical practice; 82% argue for better
      management of PONV. However, only 28% of the general surgical patients with PONV
      received sufficient antiemetic therapy. Studies demonstrate that the prophylactic
      use of antiemetics in patients at risk can lead to complete symptom control in
      85% of the cases. Combination therapy of different antiemetic strategies can
      further increase the rate up to 96%. CONCLUSION: There is a need for surgeons to
      pay more attention to patient-related symptoms.

PMID- 11824027
TI  - [Brain abscess in retroperitoneal perforated colonic diverticulitis].
AB  - The most frequent complications in diverticular disease are local abscess,
      perforation with peritoneal sepsis, fistula and ileus. Extraabdominal
      manifestation is an actual rarity. A haematogenous bacterial spread via portal
      vein with formation of liver abscess has seldom been described. But a complicated
      diverticular disease as a cause for a brain abscess is an absolute rarity. Our
      case presents a patient with brain abscess caused by asymptomatic,
      retroperitoneal perforated colonic diverticulosis. We discuss diagnostic steps
      both in diverticular disease and brain abscess and different surgical options in
      the treatment of colonic complicated diverticular disease.

PMID- 11824028
TI  - [Mechanical comparison of biodegradable intervertebral lumbar cages].
AB  - INTRODUCTION: A biodegradable interbody cage for lumbar spine fusion would be
      able to solve several problems associated with the use of metallic cages. In a
      biomechanical in vitro study using human lumbar spines three different
      biodegradable poly(L-lactide-co-D,L-lacitide)(PLDLLA) cages were compared to
      metallic cages of the same design. MATERIAL AND METHOD: 40 human cadaver lumbar
      specimens (L3-S1) were tested in flexion, extension, rotation, and bending with a
      non-destructive flexibility method using a nonconstrained testing apparatus.
      Seven different groups were examined: (1) control group (intact) (n = 40); (2)
      unstable group (after discectomy L4/5) (n = 40), (3) autologous iliac crest bone
      graft (n = 8), (4) BAK-Cage (n = 8), (5) BIO-Cage 1 (PLDLLA) (n = 8), (6) BIO
      Cage 2 (PLD-LLA/hydroxylapatite-buffer) (n = 8) and (7) BIO-Cage 3
      (PLDLLA/hydroxylapatite particles of different size) (n = 8). Additionally,
      destructive compression tests of all implants were performed. RESULTS: In
      comparison to the intact motion segment all cages showed significantly lower
      range of motion (ROM) in all test modes (P < 0.01). There was no significant
      difference in stiffness values and ROM between BIO-Cages and metallic cages.
      Axial compression stiffness and failure load were significantly highest for
      metallic BAK-cages (P < 0.05). No significant difference for failure load was
      observed between BIO-cage 1 and the intact motion segment. However, in comparison
      to the intact motion segment failure load was significantly lower for BIO-cage 2
      and 3 (P < 0.05). CONCLUSION: The results of this study are encouraging, because
      the biodegradable cages were able to limit lumbar spine motion similar to the
      metallic cages. Especially, the biodegradable PLDLLA cage consisting of pure
      polymer (BIO-Cage 1) showed adequate initial compression strength. However,
      further in vivo animal experiments are essential prior to the clinical
      application of biodegradable lumbar interbody fusion cages.

PMID- 11824029
TI  - [Therapy of soft tissue trauma in the acute phase of severe hand injuries].
AB  - INTRODUCTION: Complex hand injuries are characterized by a combination of soft
      tissue injury and additional trauma to functional structures such as nerves,
      bones, tendons, vessels and joints. A good functional result requires the
      reconstruction of the injured structures and early mobilisation. Good
      vascularized soft tissue and stable osteosyntheses are the major prerequisites to
      avoid infections and to allow early mobilisation. The optimal timing for soft
      tissue reconstruction remains controversial with respect to the incidence of
      infections. METHODS: We have evaluated retrospectively our series of complex hand
      injuries addressing the question whether a delay of soft tissue coverage for up
      to 72 hours causes significant increase of infection rates. RESULTS: 48 patients
      were treated with complex injuries of the hand within a three year period between
      December 1998 and December 2000. The lowest incidence of infections occurred in
      the group, where soft tissue coverage was completed as an emergency procedure.
      DISCUSSION: Ideally primary reconstruction of complex hand injuries should be
      strived for to minimize scar formation as a result of secondary operations and
      further immobilisation periods. This includes, if necessary, free tissue
      transfer. Exceptions are situations where the vitality of soft remains uncertain.
      In these cases, definitive surgery is delayed for a maximum period of 72 hours.

PMID- 11824030
TI  - ["High pouch output" syndrome. Role of mineralocorticoid diagnosis after
      restorative proctocolectomy].
AB  - The two-phase restorative proctocolectomy is the treatment of choice for surgical
      therapy of the familial adenomatous polyposis (FAP) and also for the ulcerative
      colitis (UC). Besides the well-known complications the entire removal of the
      colorectum leads to an impairment of fluid and electrolyte resorption. PATIENTS
      AND METHODS: Over a time period of two years we observed 320 proctocolectomized
      patients with ileal pouch-anal anastomosis (IPAA). All patients with high pouch
      output but without organic malfunction were identified. The organic reasons were
      excluded with the help of pouchoscopy, radiography or MR imaging. We evaluated
      routine parameters, the kidney function, the electrolyte changes, the acid-base
      balance and the urine pH, as well as the hormonal changes of the suprarenal
      glands. We identified seven patients with 'high pouch output' out of 320 patients
      observed. The control group consisted of 14 proctocolectomized patients without
      hints of complications in the endoscopic, radiographic and routine laboratory
      diagnostics. RESULTS: Neither group showed any significant differences in the
      analysis of the routine parameters. A significant drop of the urine sodium
      concentration of 40.5 +/- 18.7 mmol/l (control group 98 +/- 43.4 mmol/l) was
      observed in the group with 'high pouch output'. In this group the plasma
      aldosterone values were strongly increased with an average of 42.6 +/- 28.9 ng/dl
      (control group 13.2 +/- 6.8 ng/dl) as well as the plasma 18-hydroxycorticosterone
      with an average of 153.7 +/- 121.1 ng/dl (control group 153.7 +/- 121.1 ng/dl).
      Neither group of patients showed increased activity of free corticosterone and
      free cortisol. Only free 11-desoxycorticosterone was elevated in the group with
      'high pouch output'. CONCLUSION: Our results prove that the mineralocorticoid
      adrenal activity plays a central role in order to preserve the volume and
      electrolyte homeostasis. The low frequency of 'high-pouch-output'-complications
      in realms of the restorative proctocolectomy proves the excellent compensation of
      the removal of the colon mucosa. Plasma aldosterone seems to be a diagnostic
      marker encapsulating the reabsorption problems of intestinal salt and volume
      losses after proctocolectomy.

PMID- 11824031
TI  - [Surgical procedures and risk factors in therapy of benign multinodular goiter. A
      statistical comparison of the incidence of complications].
AB  - BACKGROUND: The best surgical approach for bilateral resections in the therapy of
      benign multinodular goiter is still controversial. METHODS: The purpose of this
      study was to compare different modes of resection concerning differences in
      complication rates and risk factors influencing the outcome. 2235 thyroid
      resections for multinodular goiter between 1985 and 1999 were analysed. RESULTS:
      When compared to bilateral subtotal resection (n = 327; 14.6%), those patients
      who received lobectomy and contralateral subtotal resection (n = 952; 42.6%)
      showed a statistically significant higher incidence of temporary hypocalcaemia
      (22.6% versus 15.9%) only. The "nerve at risk"-analysis demonstrated no
      significant difference of laryngeal nerve paralysis between the side of lobectomy
      and subtotal resection, respectively. In comparison to the entire patient
      population operations for recurrent goiters had an equal operative risk, whereas
      patients with goiter WHO III or an intrathoracic location had significant higher
      rates of temporary laryngeal nerve paralysis and hypocalcaemia. CONCLUSIONS:
      Lobectomy and contralateral subtotal resection offers numerous advantages
      concerning intraoperative variability and definitive resection of suspicious
      nodules. With an adequate standardized surgical technique and identification of
      the laryngeal nerve, the complication rate is comparable to bilateral subtotal
      resection.

PMID- 11824032
TI  - [Network of surgical wound centers using a new electronic data processing
      documentation system].
AB  - Care of chronic wounds is of enormous medical, social and economic importance.
      Nevertheless there is a lack of epidemiological and economical data. A network of
      ten wound care centers was created and data were documented in a new computerized
      wound documentation system. METHODS: Treatment was performed according to a
      comprehensive and standardized wound care protocol. The new documentation system
      is a network-capable solution. Digital images and planimetry as well as patient
      and wound related data are recorded. RESULTS: During the first year the ten
      centers treated and documented already 3281 wounds. There is a wide spectrum of
      different chronic wounds treated in the participating centers. Despite of long
      wound duration of several wounds with a median of 5 weeks (range 0-62 years), the
      healing rate was 80% within 455 days. CONCLUSION: Large amounts of data can be
      collected and scientifically evaluated in the wound net. This is realized by a
      new computerized documentation system, which was integrated into the clinical
      routine and enables clear and standardized documentation. Therefore even large
      multicenter therapy studies may be performed easily in the wound net and
      economical data could be collected.

PMID- 11824033
TI  - [Fournier gangrene as a rare complication after stapler hemorrhoidectomy. Case
      report and review of the literature].
AB  - Fournier's gangrene is a well known often fatal fasziitis of the pelvic floor
      following ano-rectal, urologic and gynecologic infections. Although rarely it is
      described as a complication of operative anal procedures and predisposing factors
      such as diabetes, alcoholism, immune-defects and consumptive diseases. To our
      knowledge the described case of a lethal outcome after staplerhemorrhoidectomy is
      the first one reported in literature.

PMID- 11824034
TI  - [Surgical therapy of rectal carcinoma. Portrayal of the current health care
      status within the scope of a district quality assurance study].
AB  - In an era of economic pressure, patient's participation in decision-making and
      evidence-based medicine, the need for quality assurance of medical processes in
      daily routine becomes increasingly important. The aim of this quality assessment
      study is to demonstrate the real state of surgical care of patients with rectal
      carcinoma in the context of a field study on quality management in oncology.
      METHODS: Prolective cohort-study, small-area-analysis. Between 01.01.1997 and
      31.12.1998, all patients with newly diagnosed rectal carcinoma and treatment in
      the county of Marburg-Biedenkopf (252.975 inhabitants, 3 hospitals) were included
      in the study. Documentation included all variables (n = 82) relevant for primary
      surgical therapy according to guidelines and standards. RESULTS: 146 consecutive
      patients fulfilled the inclusion criteria. 93% underwent resection of the tumor.
      In 6.6% of these cases rigid rectoscopy for determination of the tumor's distance
      from the anal verge was not performed. In 16.9% the colon was not examined
      completely. In 98.5% the state of distant metastases was documented
      preoperatively. 93% of the patients with tumors in the upper/middle third of the
      rectum and curative-intent surgery (n = 68) received a sphincter-saving
      operation. For all curative-intent procedures negative resection margins were
      confirmed histologically. Complication rates were 31.6% for anterior resection
      and 46.9% for abdominoperineal extirpation. CONCLUSIONS: Comparative analysis of
      quality indicators revealed a predominantly good quality of care. Improving
      efforts can now be concentrated on few areas of suboptimal quality in the setting
      of internal quality management. Critical results require detailed analysis of the
      single cases. Thus, conditions requiring deviation from guidelines become
      apparent.

PMID- 11824036
TI  - [Total endoscopic pre-peritoneal mesh implant in primary or recurrent inguinal
      hernias].
AB  - INTRODUCTION: Since 1994 we perform laparoscopic total extraperitoneal hernia
      repair (TEP) for primary and recurrent inguinal hernias at our institution. The
      aim of this study was to investigate and compare the results of TEP in primary
      inguinal hernias and recurrent inguinal hernias and to determine whether there
      are differences in patient data, complication rates and outcome between these two
      groups. METHODS: In a prospective trial 338 patients were analyzed who underwent
      500 laparoscopic TEP repairs. In all, 431 TEP repairs were performed for primary
      inguinal hernias, and 69 for recurrent inguinal hernias. For data acquisition the
      SALTC study protocol was used. All patients were clinically examined 3 and 12
      months after the operation. RESULTS: The mean operation time was 67.3 min for TEP
      repair of primary hernias and 68.1 min for TEP repair of recurrent hernias,
      respectively. The conversion rate to an open procedure was 0%. Conversion from
      TEP into TAPP was required in 0.5% of patients with primary inguinal hernias and
      1.4% of patients with recurrent inguinal hernias. As the sole difference between
      the two groups the intraoperative complication rate could be identified. In the
      TEP repair group of recurrent inguinal hernias a higher incidence of injury to
      the peritoneum and a higher occurrence of bleeding from the epigastric vessels
      was found (P = 0.03). The postoperative complication rate was identical in the
      two groups, amounting to 5.1% and 5.7%, respectively. No differences were found
      in the 1 year follow-up between the two groups. The 1-year recurrence rate was
      0.5% for primary hernias. However, in the group of recurrent hernias there have
      been no recurrences to date. CONCLUSIONS: The use of laparoscopic TEP repair has
      proven to be a safe and effective treatment in patients with primary and
      recurrent inguinal hernias. Because of scar tissue with possible adhesions a
      higher intraoperative complication rate was observed in the TEP repair of
      recurrent hernias than in TEP repair of primary inguinal hernias. However, no
      single recurrence was observed in the TEP repair group of recurrent hernias. In
      our opinion TEP is the optimal hernia repair for recurrent and bilateral inguinal
      hernias.

PMID- 11824035
TI  - [Laparoscopic adrenalectomy with lateral approach--a comparison with the
      conventional dorsal technique].
AB  - OBJECTIVES: Minimal invasive techniques are gaining more and more acceptance in
      adrenal gland surgery. In a matched case control study laparoscopic
      transabdominal adrenalectomy in the lateral position (LA) was compared to the
      conventional open dorsal technique (DA) with resection of the 11th or 12th rib.
      METHODS: Between July 1998 and March 2000, 26 LA in 24 patients (two bilateral)
      were prospectively documented and compared to 25 DA in 23 matched patients (two
      bilateral), who had been operated on between January 1995 and June 1998.
      Indications for adrenalectomy in all patients were benign adrenal lesions < 6 cm.
      RESULTS: Age, gender, average tumor size (3.5 cm/3.6 cm) and tumor types (Conn
      adenoma: 10/7; Cushing: 8/7, including 2 bilateral in each group;
      pheochromocytoma: 3/6, incidentaloma: 2/2; others: 3/3) were distributed in both
      groups (LA/DA) without statistical differences. However, statistically
      significant differences (P < 0.05) were present (LA vs DA) comparing
      intraoperative blood loss (200 vs 360 ml), postoperative narcotic equivalents
      (1.1 vs 6.2), morbidity (8 vs 30%), and length of hospital stay (5.5 vs 9 days).
      Average operating time was significantly longer in LA (130 vs 105 min), but
      decreased during the last LA cases to the DA level. One LA had to be converted to
      open surgery due to diffuse bleeding. Following LA we observed two minor
      complications (small retroperitoneal hematoma, nerve irritation below the 12th
      rib); following DA there were 6 minor (2 dorsal subcutaneous hematomas, 2 nerve
      irritations, dystelectasis, pleural effusion) and one major complication (wound
      infection). CONCLUSION: LA represents a safe procedure with all the common
      advantages of minimal access surgery. Based on our experience and that of others,
      laparoscopic adrenalectomy has become the gold standard for adrenalectomy in most
      cases of benign adrenal disease. As adrenal surgery is rare, at present LA should
      be restricted to centers with a special interest in endocrine and laparoscopic
      surgery.

PMID- 11824037
TI  - [Implementation of a new electronic patient record in surgery].
AB  - INTRODUCTION: The increasing amount of clinical data, intensified interest of
      patients in medical information, medical quality management and the recent cost
      explosion in health care systems have forced medical institutions to improve
      their strategy in handling medical data. In the orthopedic department (3,600
      surgeries, 75 beds, 14,000 consultations) software application for comprehensive
      patient data management has been developed. METHOD: When implementing the
      electronic patient history following criteria were evaluated: 1. software
      evaluation, 2. implementation, 3. work flow, 4. data security/system stability.
      RESULTS: In the first phase the functional character was defined. Implementation
      required 3 months after parametrization. The expense amounted to 130,000 DM (30
      clients). The training requirements were one afternoon for the secretaries and a
      2-h session for the residents. The access speed on medically relevant data
      averaged under 3 s. The average saving in working hours was approximately 5
      h/week for the secretaries and 4 h/week for the residents. The saving in paper
      amounted to 36,000 sheets/year. In 3 operational years there were 3 server
      breakdowns. CONCLUSIONS: Evaluation of the saving on working hours showed that
      such a system can amortize within a year. The latest improvements in hardware and
      software technology made the electronic medical record with integrated quality
      control practicable without massive expenditure. The system supplies an extensive
      platform of information for patient treatment and an instrument to evaluate the
      efficiency of therapy strategies independent of the clinical field.

PMID- 11824038
TI  - [Pyoderma gangrenosum after TAPP hernioplasty. A rare differential necrotizing
      wound infection diagnosis].
AB  - Pyoderma gangrenosum is an aseptic skin disease that occasionally complicates
      operative incisions and mimics postoperative necrotising wound infection. So far
      there are only a few case reports about bacterial necrotising infections
      following laparoscopy; no report exists about postoperative pyoderma gangrenosum
      after minimally invasive surgery. Differential diagnosis of both these diseases
      with potentially high morbidity and mortality is, however, essential, as they
      require opposite therapeutic regimens. Here we present the case of a patient who
      developed pyoderma gangrenosum after laparoscopic hernioplasty.
      Pathophysiological, clinical and therapeutic aspects of the disease are
      discussed.

PMID- 11824039
TI  - [Secondary spontaneous pneumothorax in tuberous sclerosis].
AB  - Secondary pneumothorax occurs as a symptom of an underlying pulmonary disease. We
      report the case of an 18-year-old woman with tuberous sclerosis (Bourneville's
      disease) and recurrent pneumothoraces. Clinical outcome was favorable 6 months
      after bilateral videothoracoscopic pleurectomy. The complete triad of tuberous
      sclerosis (TS) (mental retardation, seizures, adenoma sebacium) is not always
      present in those who develop pulmonary involvement. When TS involves the lung it
      is clinically and pathologically indistinguishable from lymphangioleiomyomatosis
      (LAM). The very rare pulmonary involvement of TS and LAM are problems primarily
      of women in childbearing age. A pneumothorax can be the first symptom of TS or
      LAM.

PMID- 11824040
TI  - [Comment on U. Guller et al.: Neurogenic appendicopathy: a common, nearly unknown
      disease picture. Evaluation of 816 appendices and review of the literature].

PMID- 11824041
TI  - [Comment on E. Kleimann and H.J. Halbfass: On the topic of the "short esophagus"
      in laparoscopic antireflux surgery].

PMID- 11824042
TI  - [Fractures of the head of the humerus].

PMID- 11824043
TI  - [DRG risk management. A strategy for reducing risk and increasing chances in the
      DRG reimbursement system].

PMID- 11824044
TI  - [Diagnostic related groups. DRG practice].

PMID- 11824045
TI  - [Responsibility for patient education also about incision in appendectomy?].

PMID- 11824046
TI  - [Not overshooting the goal: comment on the contribution "Fatal endotoxic shock
      after transfusion of autologous erythrocyte concentrate"].

PMID- 11824048
TI  - [Delegating responsibilities].

PMID- 11824049
TI  - Births, marriages, divorces, and deaths: provisional data for April-June 2001.

PMID- 11824050
TI  - A method for constructing complete annual U.S. life tables.
AB  - OBJECTIVES: This report describes a method for constructing complete annual U.S.
      life tables and for extending the age coverage of the life table to age 100.
      Previously, annual life tables were based on an abridged methodology and were
      closed with the age category 85 years and over. In the United States,
      approximately one-third of the population survives beyond age 85 years. This
      fact, coupled with improvements in age reporting and the availability of higher
      quality old-age mortality data, recommends that the life table be closed at an
      older age. METHODS: The method, similar to that used to construct the decennial
      life tables, uses vital statistics and census data to calculate death rates for
      ages under 85 years and Medicare data for ages 85 years and over. Previously, the
      annual life tables were abridged, and used only vital statistics and census data.
      CONCLUSIONS: The complete life table methodology described in this report
      produces estimates of life expectancy at ages 100 years and younger that are
      consistent with previously published life tables. Complete life tables based on
      1996 mortality data compared favorably with published 1996 abridged life tables
      and with the 1989-91 decennial life tables. The methodology was implemented
      beginning with final mortality data for 1997.

PMID- 11824051
TI  - [Role of intersphincter resection among the surgical options for cancer of the
      distal rectum].
AB  - The surgical treatment of low rectal cancer has yet to be standardised. The aims
      of the study were to define the curative role of intersphincteric resection and
      to evaluate its indications and functional results through a retrospective
      clinical experience. From 1988 to 2000, out of 783 operations for primary rectal
      cancers (resectability rate 96%; restorative resections 83% and APR 10%) an
      intersphincteric resection was performed in 48 patients (31 male, 17 female,
      average age 62) for tumours located at a mean distance of 4.5 cm from the anal
      verge. Clinical stage: 27 T3 (56.3%), 12 T2, 5 T4 and 4 T1. All the operations
      were rated R0. TME with N-S, endo-anal distal transection and manual colo-anal
      anastomosis with a protective stoma were systematically performed. The mean
      follow-up was 46 months (range: 12-80). Functional results were evaluated with a
      prospective standardised questionnaire. There was no hospital mortality (30
      days). The total morbidity rate was 22% with anastomotic leakage (clinical or X
      ray evidence) in 12.5%. Four anal stenoses needed dilatation. Only one local
      recurrence six years after operation (2.1%). Nine patients died of systemic
      metastases within 3 years of surgery; the others are still alive and disease
      free. Minor faecal incontinence with frequency and urgency occurred in 68.7% of
      cases at 3 months after protective stoma closure and in 37.5% after 6 months.
      After one year continence was good in 85.4% of survivors. Only one case required
      a permanent stoma for poststenotic total incontinence. The best functional
      results were achieved by colonic pouch reconstruction. For selected low rectal
      cancers (T2/T3) without voluntary sphincter infiltration, intersphincteric
      resection is safe and effective for oncological and functional purposes. The
      procedure requires accuracy in dissecting the anorectal junction. Preoperative
      radiotherapy may increase the indications for intersphincteric resection as well
      as the availability of a disease-free margin. A manual colo-anal anastomosis with
      colonic pouch interposition is strongly recommended.

PMID- 11824052
TI  - [Advanced age as risk factor in liver resection surgery].
AB  - To evaluate the influence of age on the outcome of liver resections, 105
      consecutive patients undergoing hepatic resection were divided into two groups:
      age > or = 65 years [Old Group (O-Group)] and age < 65 years [Young Group (Y
      Group)]. O-Group and Y-Group patients were analyzed comparatively in terms of
      primary diagnosis, concomitant diseases, previous surgery, type of operation
      (major or minor resection), associated procedures, presence and length of portal
      clamping, intraoperative blood losses and transfusions, and length of operation.
      The end points of the study were postoperative mortality, morbidity,
      transfusions, and length of post-operative hospitalization. The Y-Group included
      61 resections in 60 patients, with a mean age of 52 +/- 10 years (mean +/- SD),
      range 23-64 years, and the O-Group 44 resections in 43 patients, with a mean age
      of 71 +/- 4 years, range 65-82 years. The O-Group included more cases of hepatoma
      (45.4% vs 18%, p = 0.002) and cirrhosis (40.9% vs 18.7%, p = 0.017). Median
      length of operation was slightly higher in the Y-Group (330 vs 270 minutes, p =
      0.003). The O- and Y-Groups were comparable (p = n.s.) when evaluated for all
      other variables listed. As regards the end points of the study, length of post
      operative hospitalization was identical in both groups (median 9 days, range 5-60
      days) and neither PRBC transfusions (O-Group vs Y-Group: 16% vs 25%) nor FFP
      transfusions (O-Group vs Y-Group: 13.6% vs 6.5%) showed any statistically
      significant difference. Postoperative mortality consisted in 1 death among the
      younger patients while no deaths were recorded among the older patients.
      Postoperative morbidity was higher in the Y-Group than in the O-Group (31.1% vs
      20.5%, p = 0.59). Advanced age does not negatively affect the outcome of liver
      resections.

PMID- 11824054
TI  - [Assessment of the adequacy of health services in day hospital care: experience
      of an endocrine surgery day care unit at a university polyclinic].
AB  - The aim of the study was to assess the appropriateness of the provision of
      surgical treatment in the day hospital setting and at the same time to evaluate
      the efficacy of the service provided. The study was conducted on admissions to a
      day care unit operating in conjunction with the surgery division of a university
      hospital. The evaluation of appropriateness was carried out using explicit
      criteria, based on regional regulations and on guidelines drawn up by the Agency
      for Regional Health Services. The criteria related to the hospital bed equivalent
      Rotation Index and to the types of DRGs treated and services provided. Efficacy
      was assessed using the following para-meters: number of US-guided fine needle
      aspiration biopsies; techniques used; age, sex and nodule size; patient
      distribution by results of diagnostic examination; cytological classification;
      percentage of patients with complications. We also evaluated the possibility of
      transferring short-term (2-3 days) surgical admissions from ordinary regimens to
      the day care setting. The results of this study yield useful synthetic indicators
      for assessing the appropriateness both of the day care function as a whole and of
      individual operating units, providing both administrative and medical staff with
      a useful frame of reference for the planning of health-care management.

PMID- 11824053
TI  - [Acute hemorrhage secondary to gastric ulcer. Results of emergency endoscopic
      treatment in 775 cases].
AB  - The aim of this study was to investigate the effects of endoscopic injection
      therapy on the clinical outcome of patients with gastric ulcer bleeding. Seven
      hundred and seventy-five patients with gastric ulcer bleeding were observed over
      a 10-year period (January 1990 to May 2000) in the First Division of General
      Surgery of the University of Verona. The prognostic and therapeutic implications
      of endoscopic treatment of acute severe gastrointestinal bleeding were analyzed
      on the basis of medical history and clinical and endoscopic findings. The ulcers
      were classified according to Forrest's classification of bleeding activity.
      Endoscopic therapy was performed in 500 patients with active bleeding.
      Haemostasis was initially obtained in all patients except one. Rebleeding
      occurred in 13%. All these patients were treated endoscopically at the first
      attempt. Multivariate analysis revealed that recent surgery, ulcer site and
      Forrest classification independently influenced the recurrence rate. The
      mortality of the entire cohort studied was 8.1%. Only 31 patients (4%) underwent
      surgical treatment with a higher mortality compared to unoperated patients (19.3%
      vs 7.7%). Endoscopic treatment is a safe procedure with a low mortality and cost,
      and, if successful, substantially reduces the need for emergency surgery.

PMID- 11824055
TI  - [Radical surgery for gallbladder carcinoma].
AB  - The aims of the study were to evaluate the adequacy of the surgical treatment and
      results of curative extended resections for gallbladder cancer. To this end we
      carried out a retrospective analysis of 59 patients operated on at our
      institution from 1983 to 2000. Nineteen patients received a curative resection
      with a radical intent (4 stage I-II patients and 15 stage III-IV patients,
      according to the AJCC classification). Kaplan-Meyer survival was 100% after one
      year and 66.6% after five years for stage I-II patients; 44.4% after one year and
      0% after 5 years for stage III patients; 75.0% after one year and 0% after 5
      years for stage IV patients. Our analysis confirms the poor prognosis of
      gallbladder carcinoma. In stage I-II patients surgical treatment offers a good
      chance of survival. In stage III-IV patients surgery affords good palliation.
      "Curative" extended resection is, however, a safe surgical procedure and offers a
      real possibility of enhancing survival.

PMID- 11824056
TI  - [Our experience in the surgical treatment of gastrointestinal stromal tumors].
AB  - The authors carry out a retrospective review of 30 patients with gastrointestinal
      stromal tumours (GISTs) who underwent surgical treatment over the period from
      1974 to 2001. Sixteen were male and 14 female, with an average age of 60.9 years.
      Histologically, 19 tumours showed evidence of differentiation towards smooth
      muscle elements (10 benign and 9 malignant), 9 towards neural elements (3 benign
      and 6 malignant) and 2 iacked differentiation towards either cell type. Twenty
      one tumours were located in the stomach, 1 in the duodenum, 3 in the jejunum and
      5 in the ileum. The main symptoms were abdominal pain and abdominal masses, and
      the most sensitive diagnostic techniques were abdominal CT scan and endoscopy in
      gastroduodenal locations. In 21 gastric GISTs, the surgical procedures were local
      resection (15 cases), partial gastric resection (3 cases), subtotal gastrectomy
      (2 cases) and total gastrectomy (1 case). In 8 small bowel GISTs, we performed a
      typical intestinal resection while duodenal undifferentiated GIST was managed by
      pancreatico-duodenectomy. There was no operative mortality or morbidity. Among
      the 13 patients with benign GISTs, 1 died of causes unrelated to the disease,
      while 12 patients are still alive and in good health after a mean follow-up of
      148.5 months (range: 6-262). Among patients with malignant muscular GISTs (6
      gastric and 3 ileal), 3 with gastric tumours were lost to follow-up, 3 with
      gastric and 1 with ileal neoplasms are alive and free from disease after a median
      follow-up of 58 months (range 3-108), while 2 patients with ileal neoplasms died
      of metastatic disease 39 and 29 months after the surgical procedure. Among 6
      patients with malignant neural GISTs (2 gastric, 2 jejunal and 2 ileal) 1 with a
      gastric tumour and 1 with a jejunal tumour were lost to follow-up, while 3 are
      still alive and in good health after a median follow-up of 67.6 months (range 19
      to 94); another with jejunal disease developed liver metastases 14 months after
      small bowel resection and died 12 months later. The two patients with
      undifferentiated GIST both died of liver metastasis 38 months after pancreatico
      duodenectomy and 43 months after total gastrectomy. The most frequent symptoms
      were abdominal pain and a palpable mass, but no specific signs were detected. In
      gastroduodenal lesions endoscopy plays a very important diagnostic role and CT
      scan is the most sensitive diagnostic technique in the evaluation of location,
      size, invasion of adjacent organs and metastases. Prognostic prediction on the
      basis of histological findings is difficult and in our experience
      undifferentiated tumours are always malignant.

PMID- 11824057
TI  - Laparostomy in the treatment of severe peritonitis: a review of 60 cases.
AB  - The aim of this study was to evaluate the use of laparostomy in the management of
      patients with severe abdominal infections. From June 1992 to December 2000 sixty
      patients with severe peritonitis were treated with laparostomy and studied
      retrospectively. Thirty-eight had post-operative peritonitis. Twelve patients had
      necrotic pancreatitis. Five patients had peritonitis due to ischemic colitis. Two
      patients had hemoperitoneum following multiple abdominal operations, and three
      patientshad severe wound dehiscence. The APACHE II score was used to determine
      the severity of patients' condition. The median age was 46 years, the mean APACHE
      II score was 19.7, and the observed mortality was 38.3%. The incidence of
      spontaneous fistulation of the exposed loop of intestine was 13.3%. In 11
      patients abdominal wall closure was accomplished by primary intention. Incisional
      hernias were inevitable in the rest of patient and were repaired 1 years after
      surgery. Laparostomy is a good way to manage patients with severe peritonitis but
      it should be performed before irreversible septic shock and subsequent multi
      organ failure develop.

PMID- 11824058
TI  - [Early colorectal reoperation: risk factors].
AB  - The aim of the study was to analyse the risk factors in colorectal reoperation.
      Over the period from January 1987 to December 1999, 371 patients (191 male and
      180 female, aged from 16 to 88 years) underwent colorectal surgery. Eighteen
      reoperations (12 male, 6 female, aged from 20 to 74 years; median age: 52.6
      years) were performed. These included reoperations performed within 30 days of
      the first operation (or patient admission). The overall incidence of reoperation
      after colorectal surgery was 4.8% (18/371). In 14 of 18 patients (77%)
      anastomotic dehiscence was the indication for reoperation. In our experience, the
      mortality rate was 16.6% (3/18), in agreement with other reports in the
      literature. Analysis of risk factors in colorectal reoperation poses several
      methodological problems because we have no randomized multicentre studies that
      analyse risk factors in colorectal reoperation and the related surgical
      mortality.

PMID- 11824059
TI  - [Use of mechanical staplers for the solution of proctological problems. Our
      experience with 122 patients].
AB  - The Longo technique using a circular stapler has changed haemorrhoid therapy.
      Thanks to the advent of this technique for treating haemorrhoids without
      excision, we can now successfully eliminate the mechanism responsible for their
      pathogenesis. The aims of circumferential stapled anoplasty are to correct the
      anodermal prolapse and restore the haemorrhoidal cushions to their anatomical
      position. Furthermore, with a few variants the technique can be utilised for
      other proctological problems, such as obstructed defecation in rectocele and
      incomplete internal prolapse (or rectal intussusception). The authors report on
      their experience in a consecutive series of 122 cases undergoing circular stapled
      anoplasty for haemorrhoids, associated in 10 cases with rectocele or rectal
      intussuscep-tion, analysing early and late complications after an accurate follow
      up. The procedure can be performed with local or spinal anaesthesia. The
      operation lasted on average 19 minutes. There were few complications: early
      bleeding (4.9%), late bleeding (0.8%), mild stricture (2.5%) and thrombosis of
      external piles (8.2%). This new surgical technique is effective and rapid, causes
      only minimal postoperative pain and could be proposed as an alternative to
      traditional surgery also in the day surgery setting.

PMID- 11824060
TI  - [Videolaparoscopic treatment of varicocele: retrospective study of 165 cases].
AB  - Idiopathic varicocele is a common condition that is present in approximately 15%
      of the general male population. The mechanism by which varicocele exerts a
      deleterious effect on testicular function and semen quality remains unknown.
      Nevertheless, it is generally regarded as a significant factor in male
      infertility. Varicocelectomy is accomplished with a variety of approaches: the
      inguinal and high retroperitoneal procedures are still commonly accepted methods,
      but laparoscopic varicocelectomy is currently proving an increasingly popular
      procedure. The authors report the results of a retrospective study of 165
      laparoscopic varicocelectomies performed from 1993 to 2000 and conclude that this
      approach is simple, safe and effective and should be recommended as the treatment
      of choice.

PMID- 11824062
TI  - Sentinel node biopsy for breast cancer: a critical analysis.
AB  - The concept of sentinel node biopsy, initially introduced for melanoma, has also
      been used for breast cancer since the 90's, in that, with the increasingly,
      widespread use of mammographic screening and of other minimally invasive
      diagnostic procedures, smaller and smaller cancers are now being diagnosed. For
      these cancers axillary dissection often constitutes overtreatment. For cancers at
      an initial stage with a low risk of axillary metastases investigation of sentinel
      lymph nodes enables us the surgeon to assess the axillary lymph-node status and
      avoid axillary dissection which is responsible for a certain amount of morbidity.
      Sentinel nodes can be sought using colorimetric or radioisotope methods. To date
      there is no common consensus of opinion as to which is the better procedure and
      the respective indications. Both methods allow detection of sentinel nodes in
      roughly 90% of cases and the combination of the two yields 100% detection rates.
      It is widely accepted that sentinel node biopsy should be reserved for unifocal
      tumours which have not been treated previously and which measure less than 15 mm
      in diameter. The advantages of the procedure are substantial provided it is
      performed correctly by surgeons properly trained in its use. The learning curve
      is relatively brief and is based on no more than 30-40 cases.

PMID- 11824061
TI  - [Laparoscopic appendectomy as first choice intervention in the treatment of
      inflammatory diseases of the appendix. Analysis of 397 laparoscopic
      interventions].
AB  - Despite the increasingly widespread use of laparoscopy, especially for
      gallbladder diseases, laparoscopic appendectomy has not yet met with universal
      acceptance. The aim of the present retrospective study was to illustrate the
      technical aspects and the results of 397 laparoscopic appendectomies carried out
      at the Surgical Department of the San Giovanni Battista Hospital in Zagarolo,
      Rome, from January 1993 to December 2000. The patients included 260 females with
      a mean age of 35.5 years and 137 males with a mean age of 38.5 years. All the
      appendectomies were carried out laparoscopically, with a conversion index of 0%,
      by two surgeons, utilising only three trocars and the Veress needle technique.
      Mean operating time was 22.5 min (range: 15-30 min). The mean postoperative
      hospital stay was 1.5 days. Morbidity was 1.76% (7 cases) and mortality nil. The
      authors emphasise the numerous advantages of laparoscopic techniques in their
      experience, including the excellent cosmetic results, reduced postoperative pain,
      rapid functional recovery, and lower incidences of adhesions, wound infections
      and laparocele, and believe that laparoscopic appendectomy is a reliable
      operation for treating all inflammatory diseases of the appendix.

PMID- 11824063
TI  - [Spigelian hernia].
AB  - The Authors report their experience with the treatment of Spigelian hernia. After
      addressing the anatomy of the abdominal lateral wall and of etiopathogenic
      factors responsible for this rare type of hernia, the clinical problems
      associated with the disease are discussed and the importance of physical
      examination and instrumental procedures is stressed. The authors then go on to
      list the possible repair techniques currently available.

PMID- 11824064
TI  - [Update on animal models for testing innovative antineoplastic strategies: the
      mammary tumor in dogs].
AB  - In this study, the authors describe a new possible animal model to test new
      anticancer therapies. The selected animals are domestic animals such as dogs,
      which develop spontaneous tumours very similar in morphology and biology to human
      ones, also in relation to similar environmental oncogenic pressures. Cycline D1
      overexpression, which has both a prognostic and pathogenetic value, is usually
      detected in human tumours. Thus, the use of cycline-dependent kinases inhibitors
      could be of value in anticancer therapy. We studied spontaneous canine mammary
      tumours in order to test the above hypothesis. Immunohistochemistry, AgNOR and
      western blotting analysis were performed, and the results revealed that cycline
      D1 is associated with metabolic, morphological and protein expression patterns
      typical of proliferating cells. The same protein expression pattern, the use of
      human antibodies for detecting canine proteins and the availability of neoplastic
      tissue make these spontaneous canine tumours a reliable model.

PMID- 11824065
TI  - A rare gastric ulcer complication: the gastrocolic fistula. A case report.
AB  - We report a case of gastrocolic fistula following a benign gastric ulcer, which
      is now a truly exceptional finding, due to the widespread use of H2-receptor
      antagonists and proton- pump inhibitors. A review of the literature shows that
      this condition warrants a complete diagnostic work-up to exclude more ominous
      underlying diseases. Careful attention to the symptoms of peptic ulcer and
      particular care with patients undergoing long-term treatments with drugs
      potentially harmful for the stomach are recommended.

PMID- 11824066
TI  - Malignant schwannoma of the rectum: a clinical and pathological contribution.
AB  - Schwannomas of the rectum are uncommon and incompletely characterized tumours,
      and only a limited number of cases have been reported. On the basis of a case of
      rectal schwannoma and a review of the literature on this rare condition, we
      stress the importance of the clinical features, diagnostic difficulties and
      surgical indications for the various therapeutic approaches. The basis for
      radical operation, due to the tendency of such tumours to recur locally and the
      real possibility of malignant degeneration, is discussed. We also emphasize the
      difficulty of making a benign diagnosis with histological certainty.

PMID- 11824067
TI  - Carcinoid of the ileocaecal valve: a case report.
AB  - The authors present a case of carcinoid of the ileocaecal valve. The patient
      complained for over one year of mild pain in the right lower quadrant of the
      abdomen. Colonoscopy had shown hyperaemia on the colic side of the ileocaecal
      valve which appeared substenotic and biopsy revealed micronodules formed by
      chromogranin-A-positive neuroendocrine cells. Roentgenography of the small bowel
      and barium enema revealed a specular filling defect in the caecum and in the
      terminal ileum near the ileocaecal valve. Right hemicolectomy was performed and
      the definitive diagnosis was carcinoid of the ileocaecal valve. The tumour had
      spread to all layers of the intestinal wall and 4/19 lymph nodes were metastatic.
      The patient refused an oncological examination; however, three years after
      surgery there are no signs of recurrence. Carcinoids have been included in the
      APUD system and usually present endocrine activity. The 5-year survival of
      patients with gastrointestinal carcinoids is 80% when located in the appendix and
      rectum as against 50% in the stomach, jejunum and colon, because the localisation
      in the appendix and rectum is marked by clinical signs of appendicitis and rectal
      bleeding, which suggest diagnostic examinations useful for an early diagnosis.
      Radical operations according to the rules of oncologically correct surgery are
      the treatment of choice, while complementary treatments have yet to be codified.

PMID- 11824068
TI  - [Duodenal duplication. Report of 2 cases in adults and review of the literature].
AB  - Two cases of adult male patients with symptomatic duodenal duplication cysts are
      reported. The clinical manifestations were vomiting and epigastric pain in the
      first case and recurrent pancreatitis with a palpable mass in the right upper
      quadrant of the abdomen in the second. In both cases the diagnosis was only
      histological and the patients recovered after local excision of the duplication
      and duodenopancreatectomy, respectively. These two cases prompted an evaluation
      of the diagnostic features and surgical treatment of duodenal duplication cysts.

PMID- 11824069
TI  - [Abdominal actinomycosis and retroperitoneal fibrosis. Considerations on a
      clinical case].
AB  - Abdominal actinomycosis is a rare disease which often resembles an acute
      suppurative infection or/and abdominal tumour causing abscesses, fistulas and
      massive fibrosis. The preoperative diagnosis is difficult and surgical
      exploration is always needed because of major involvement of visceral and
      retroperitoneal structures. The disease can be diagnosed with certainty only on
      the basis of findings of bacterial colonies in histopathologic sections and
      typical sulphur grains in secretions from fistulas. The authors describe a case
      of abdominal actinomycosis involving the caecum and right colon, causing
      extensive retroperitoneal fibrosis and a fistula tract with an external cutaneous
      orifice at the level of the right iliac crest. These features resembled an acute
      appendicitis at first, and several surgical explorations were required before a
      correct diagnosis could be achieved. Abdominal actinomycosis can be treated by
      simple administration of antibiotics. With a correct diagnosis, medical therapy
      alone has proved effective in a substantial percentage of patients, thus avoiding
      the need for surgery, if important visceral or retroperitoneal structures are not
      involved. Abdominal actinomycosis always requires a careful differential
      diagnosis and must be considered in patients presenting abdominal tumours
      associated with abscesses and/or fistulas since early and efficient medical
      therapy, along with surgical intervention, where necessary, can lead to
      definitive recovery. Useful diagnostic tools are abdominal CT and selective FNAB.

PMID- 11824070
TI  - [Videolaparoscopic adrenalectomy in an unusual case of adrenal mycetoma].
AB  - The authors report a rare case of mycetoma of the adrenal gland. Mycetoma is a
      chronic, localized, non-contagious infection of cutaneous and subcutaneous tissue
      characterized by tumefaction, aggregates of aetiological agents (Actinomyces or
      true fungi). Sometimes an unusual site (other tissues or organs) is described in
      the literature, but to date no cases of adrenal gland mycetoma have been
      reported. The treatment of choice is surgical with associated penicillin and/or
      antifungal drugs. In the case reported surgical treatment is performed with a
      laparoscopic approach. This technique constitutes the gold standard in cases of
      benign neoplasms of the adrenal gland and incidentalomas. This therapeutic choice
      is open to criticism if a malignant neoplasm is suspected.

PMID- 11824071
TI  - [Fournier's gangrene in a patient with Hodgkin's disease: a clinical case].
AB  - The authors report a case of Fournier's gangrene in a 54-year-old patient
      subjected 6 days earlier to chemotherapy for mediastinal Hodgkin's disease. The
      patient had fever and reported the onset of worsening pain and heat sensations in
      the inguinal, perineal and scrotal areas. Objectively, there was local oedema
      followed by the onset of crepitation. The patient had a very low white blood cell
      count (900/cu.mm). The Patient underwent emergency surgery with multiple,
      communicating incisions in the inguinal, perineal and scrotal areas, with the
      removal of necrotic tissue and daily washing with physiological solution and 12%
      H2O2. He also received antibiotic treatment with metronidazole and gentamicin and
      5 cycles of high-pressure oxygen therapy, with disappearance of pain and fever
      and good local tissue repair.

PMID- 11824072
TI  - [Combined dissector for laparoscopic esophageal myotomy: introduction of a
      prototype of dedicated instrumentation].
AB  - The authors' aim in this article is to present the use of a combined dissector,
      devised, designed and patented by themselves, for laparoscopic oesophageal
      myomectomy in achalasic patients. The prototype was produced by Karl Storz
      Endoskope. This tool has a stem measuring 10 mm in diameter, with an operative
      push rod consisting of two upward bent jaws and an electrode that can emerge from
      the jaws as required by the surgeon. The authors used the dissector in two
      patients with a surgical achalasic mega-oesophagus. The two jaws can dissect and
      then divide the oesophageal muscular layer from the submucosal layer, whereas the
      electrode can cut the muscular fibres. The use of the combined dissector allows
      the surgeon to perform oesophageal myomectomy easily, with efficacy and safety,
      using only the right hand. The instrument requires a number of minor changes
      which are currently being planned.

PMID- 11824073
TI  - [Neuronal apoptosis. A new means of treatment for cerebral ischemia?].

PMID- 11824074
TI  - [Neuronal apoptosis following cerebral ischemia. Basis, physiopathology and
      treatment strategies].
AB  - Neuronal injury following cardiac arrest (global cerebral ischaemia) and stroke
      (focal cerebral ischaemia) is one of the major causes of the high morbidity and
      mortality associated with these pathological events. One of the major
      characteristics of this kind of neuronal injury is delayed neuronal degeneration.
      An increasing body of evidence indicates that apoptosis (programmed cell death)
      is involved in this process after global and focal cerebral ischaemia. In
      contrast to necrosis, which is primarily characterised by cellular metabolism
      failure and loss of membrane integrity, apoptosis represents a pattern of cell
      death in which an active energy-dependent cell death programme is initiated
      without any concomitant inflammatory reaction. Based on the knowledge that
      apoptosis plays a major role in delayed neuronal death following cerebral
      ischaemia, a variety of new neuroprotective therapeutic strategies have emerged
      (e.g. caspase inhibitors, viral anti-apoptotic proteins, modulation of systemic
      anti- and pro-apoptotic protein expression and death receptor antagonists). Many
      of these are still being experimentally evaluated. Relevant anti-apoptotic and
      neuroprotective therapeutic strategies could be introduced into clinical practice
      in the near future. The field of anaesthesiology will benefit from these
      important developments. New therapeutic opportunities might also become available
      in emergency medicine and critical care medicine. This article reviews the
      molecular basis of apoptosis and its physiological and pathophysiological
      relevance. The mechanisms of delayed neuronal death following focal and global
      cerebral ischaemia are presented with particular emphasis on the role of
      apoptosis. Based on this, possible future therapeutic interventions are
      highlighted and discussed.

PMID- 11824075
TI  - The Narcotrend--a new EEG monitor designed to measure the depth of anaesthesia. A
      comparison with bispectral index monitoring during propofol-remifentanil
      anaesthesia.
AB  - INTRODUCTION: The Narcotrend is a new EEG monitor designed to measure the depth
      of anaesthesia based on a 6-letter classification from A (awake) to F (general
      anaesthesia with increasing burst suppression) and divided into 14 substages (A,
      B0-2, C0-2, D0-2, E0,1, F0,1). This study was designed to investigate the
      assessment of the depth of anaesthesia as measured by the Narcotrend in
      comparison with bispectral index monitoring (BIS). METHODS: Both BIS and
      Narcotrend EEG electrodes were positioned on the patient's forehead as
      recommended by the manufacturers. All patients were premedicated with diazepam
      0.15 mg/kg orally in the evening and on the morning before surgery. Induction of
      anaesthesia was started with a remifentanil infusion at 0.4 microgram/kg/min; 5
      min later propofol was given for hypnosis using a target-controlled infusion
      initially started at 3.5 micrograms/ml. After loss of consciousness patients
      received 1.2 mg/kg of suxamethonium. Immediately after intubation, remifentanil
      was reduced to 0.2 microgram/kg/min, and the depth of anaesthesia was adjusted
      according to clinical needs by regulating the propofol target-controlled
      infusion. BIS values and Narcotrend stages were recorded as data pairs in
      intervals of 1 min during anaesthetic induction and emergence, and in intervals
      of 5 min during maintenance of anaesthesia. RESULTS: Fifty patients undergoing
      orthopaedic surgery were studied and 2031 data pairs were obtained. An increasing
      depth of anaesthesia as indicated by the Narcotrend was associated with
      significantly lower mean BIS values. With BIS values between 100 and 85
      (representing awake patients), 95.5% of all data pairs indicated a Narcotrend
      stage A or B. In case the BIS was found to be 65-40 (representing general
      anaesthesia) the corresponding Narcotrend stages were measured as D (52.4%) or E
      (41.1%). No patient complained of intraoperative recall when interviewed on the
      1st and 3rd postoperative day. CONCLUSIONS: We could demonstrate that an increase
      of the hypnotic component of anaesthesia as indicated by BIS is accompanied by
      corresponding effects as displayed by the Narcotrend during propofol-remifentanil
      anaesthesia. The Narcotrend stages D or E are assumed equivalent to BIS values
      between 64 and 40 indicating general anaesthesia.

PMID- 11824076
TI  - [Massive transfusion with the Rapid Infusion System. Its effect on core body
      temperature].
AB  - Extensive blood loss requires adequate volume replacement. However the infused
      volume cannot be adequately warmed especially when high infusion rates are
      necessary. Subsequently, hypothermia develops and results in hemodynamic
      instability and coagulopathy. The Rapid Infusion System (RIS) allows high
      infusion rates (up to 1.5 l/min) while at the same time guaranteeing sufficient
      warming. The efficacy of the RIS was investigated in 43 consecutive patients who
      required a massive transfusion. The average volume transfused in these patients
      was 31.7 +/- 4.5 l (minimum: 7.8 l; maximum: 165.3 l) which is equal to an
      average exchange of 6.4 times the circulating blood volume (maximum: 39.4 blood
      volumes). The replacement of such high blood volumes has not yet been published
      in a series of patients. Despite these high transfusion rates, the body core
      temperature was maintained at 35.85 +/- 0.1 degrees C. Only five patients had a
      body core temperature below 34 degrees C, all were trauma patients and four of
      these five patients already had a preoperative temperature below 34 degrees C.
      The mortality in this study was 28%, which is markedly reduced in comparison to
      previous publications although they all considered at patients with significantly
      less blood loss. Maintaining normothermia and normovolemia by the use of the RIS
      may explain the improved outcome.

PMID- 11824077
TI  - [The TRALI syndrome--a life-threatening transfusion reaction].
AB  - Transfusion related acute lung injury (TRALI) is a serious complication of blood
      transfusion, characterized by non-cardiogenic lung oedema. We describe a case of
      TRALI due to granulocyte-specific antibodies. The 58-year-old patient received 2
      units of fresh frozen plasma following colon surgery and within 30 min the
      patient developed an acute respiratory distress syndrome. Granulocyte-specific
      antibodies were found in one of the transfused plasma of a female blood donor who
      most likely became immunized against granulocyte alloantigens during her three
      pregnancies.

PMID- 11824079
TI  - [Coronary arterial stent implantation proceeding noncardiac surgical procedures.
      Is it safe; can we recommend it?].
AB  - Patients undergoing non-cardiac surgical procedures who carry coronary artery
      stents have to be classified as high risk patients. Perioperative myocardial
      infarction and severe bleeding are possible. Therefore, anaesthetic management
      directed by invasive monitoring, ECG ST analysis, transesophageal
      echocardiography and referral to an intensive care unit are absolutely justified.
      The urgency of the surgical procedure, perioperative risk and an antiplatelet
      regimen have to be discussed with the patient and the surgeon in advance. In the
      case of cardiac complications, rapid therapy by an interventional cardiologist
      must be available.

PMID- 11824078
TI  - [Transtracheal oxygenation in respiratory tract obstruction from a hypopharyngeal
      tumor].
AB  - A 42-year-old male with a history of chronic alcoholism was admitted to the
      department of otolaryngology with acute respiratory insufficiency and generalised
      cyanosis due to a respiratory obstruction by a large tumour of the hypopharynx.
      Because of the size and location of the tumour and the risk of bleeding,
      orotracheal intubation by direct laryngoscopy was considered almost impossible.
      To improve oxygenation cricothyroidal punction and oxygen insufflation was done
      immediately and SpO2 increased from 56% to 82%. Awake fiberoptic nasotracheal
      intubation was performed under topical anaesthesia, then general anaesthesia was
      induced and controlled ventilation was started. After surgical tracheotomy the
      patient was transferred to an intensive care unit and 12 h later the patient was
      discharged from the ICU.

PMID- 11824080
TI  - [Private liquidation of emergency patients].

PMID- 11824081
TI  - [Informed consent in obstetrical epidural analgesia. Commentary on the paper of
      T.W. Goecke et al. in Der Anaesthesist (2001) 50: 517-521].

PMID- 11824082
TI  - [Measurement of anesthesia, awareness and EEG. Remarks on the paper of M.
      Daunderer and D. Schwender, Anaesthesist (2001) 50:231-241].

PMID- 11824083
TI  - [Anesthesia for transurethral bladder resection].

PMID- 11824085
TI  - [The Nobel Prize for medicine 2001. Checkpoint cell cycle].

PMID- 11824084
TI  - [Anesthesiologic management of patients with acute porphyria].

PMID- 11824086
TI  - Diagnostic tools for ACL tears.

PMID- 11824087
TI  - Update on CPR and emergency cardiac care.

PMID- 11824088
TI  - What impact on PA education? A snapshot of ambulatory care visits involving PAs.
AB  - This study uses data from the 1997 National Ambulatory Medical Care Survey and
      the National Hospital Ambulatory Medical Care Survey to describe nonfederal
      physician office, hospital outpatient, and emergency department visits involving
      physician assistants (PAs). Of an estimated 959 million visits to health care
      practitioners, 2.55% (an estimated 24,532,000) involved PAs. Diagnoses associated
      with ambulatory care visits involving PAs included well-infant and well-child
      examinations and the care of uncomplicated injuries or wounds and respiratory
      tract infections. On average, 3.1 medications were ordered or provided at a visit
      with a PA. The problems that PAs address are similar across the 3 ambulatory care
      settings analyzed, with some expected variation between physician office and
      emergency department visits. Generally, ambulatory care visits with PAs mirror
      visits with all health care providers who practice ambulatory care medicine. PA
      education programs should ensure that students can competently perform the skills
      needed for typical ambulatory care practice.

PMID- 11824090
TI  - How to land the job you want.

PMID- 11824089
TI  - Diagnosing liver disease in asymptomatic patients.

PMID- 11824092
TI  - Adjusting to a new normal.

PMID- 11824091
TI  - A new era for the Pap test.
AB  - Utilization of liquid-based Pap testing is a significant improvement in women's
      health care. Increased diagnostic sensitivity and improvement of specimen
      adequacy are seen with its use. When combined with HPV testing, the uncertainty
      associated with waiting for additional testing is eliminated and additional
      unnecessary procedures, such as colposcopy, can be reduced. This relatively
      simple collection system will allow significant advances in molecular
      epidemiology and, in the future, development of a molecular Pap test.

PMID- 11824093
TI  - [Morbidity and cause of death in homeless persons].
AB  - The Hamburg Institute of Forensic Medicine analysed 388 deaths of homeless people
      between 1990 and 1998 considering demographic data, post-mortem results and
      autopsy findings. The manner of death was either unnatural or unascertained; the
      autopsy rate amounted to 43.8%. The results confirm the observation discussed in
      the last few years that homeless people are usually in a poor state of health. In
      relation to the average age of death, which is 44.5 years, the number of previous
      diseases is high. Unnatural causes (excluding homicides) account for a high
      percentage, viz. 62.6%, primarily intoxications. The most frequent natural cause
      of death is infection (16.8%). Women account for 8.5% of the deaths with their
      organ findings and causes of deaths being different from those of homeless men in
      terms of distribution and incidence. The data presented in this report may be
      helpful for the improvement of the present system of medical help in Hamburg.

PMID- 11824094
TI  - [Suicide bomber using a pipe bomb].
AB  - Suicidal deaths caused by pipe bombs are rare. An 18-year-old man was found dead
      in a forest by hikers. In immediate proximity to the body, a crater was located
      obviously induced by a detonation. The postmortem examination revealed severe
      damage of the head, upper-body and both arms and hands along with the extensive
      presence of soot and dirt. Particularly noticeable were numerous "entry wounds"
      and the presence of five bullet like pieces of metal in the body. The young man
      had a history of drug abuse and psychiatric problems. On the basis of autopsy
      findings, the conclusions of the police investigation and psychopathological
      considerations regarding the victim's case-history, discussion centers upon the
      differentiation between suicide by self-explosion, homicide by explosion or death
      as a consequence of numerous bullet wounds followed by an attempt to burn the
      body. Also considered is the possibility of paranoid psychosis induced by
      cannabis use as a cause of suicide.

PMID- 11824095
TI  - [Evidence for use of electroshock devices].
AB  - The authors tested whether use of an electro shock weapon (stun gun) leaves marks
      on skin which can be found in an exterior examination. On pig skin such marks
      could not be produced postmortally. An experiment on one of the authors caused
      reddish skin marks which persisted for about 2 h. Inability to act as promised by
      the weapons' manufacturers did not occur in our experiments, exactly as
      previously described by other authors. Use of an air tester which shoots barbed
      electrodes ought to produce bleedings if the electrodes actually penetrate the
      skin.

PMID- 11824096
TI  - [Satellite dish as source of electric current. Case report of a fatal and nearly
      fatal accident at the work site].
AB  - The authors report on an initially unrecognized fatal accident caused by electric
      current at the place of work. The source of the current was a satellite dish
      which had been improperly connected to an old music box with subsequent
      connection to the household electrocution system (220 V, 50 Hz). Only when a
      second nearly fatal accident occurred, proper diagnosis and detection of the
      uncommon source of the electric current was made.

PMID- 11824097
TI  - [Self-mutilation in men--injury pattern and motivation].
AB  - 6 cases of self-inflicted injuries in male individuals are reported. The age of
      the affected men was between 15 and 46 years whereas the younger age
      predominated. Alleged incidents were robberies in 3 cases, rape in one case,
      violation in custody in one case and an assault originating in personal motives
      in one case. In 4 cases, the typical injury pattern of self-infliction was
      present showing parallel course and superficiality of the wounds in areas
      accessable by the persons's own hands. In 2 cases, atypical injuries (i.e. deep
      cuts and massive signs of strangulation respectively) were found. However, in
      most cases, the underlying motive was to gain affection. An autoerotic accident
      was tried to be disguised in one case. Profit was the leading motive in another
      case.

PMID- 11824098
TI  - [Forensically relevant unexpected delivery after unrecognized or denied
      pregnancy].
AB  - The authors report on two cases of supposed unknown pregnancy, in which the
      newborns were found dead in the lavatory by the emergency physician. Besides the
      classical questions of newborn's autopsies concerning vitality, viability and
      cause of death, position was to be stated towards the probability of an
      unexpected birth. In the first case the mother's statement of not having been
      aware of her pregnancy was plausible considering the general circumstances such
      as corpulence, continued bleedings and intact family situation; autopsy proved a
      (rare) twin stillbirth as a result of fetal hypoxaemia caused by grave placental
      dysfunction and misinsertion of the umbilical cord. Contrary to this, in the
      second case, a live birth, a denial of pregnancy was more likely to be assumed
      due to misinterpretation of typical symptoms of pregnancy in combination with
      professional and private stress.

PMID- 11824099
TI  - [Unilateral occurrence of blowfly maggots in the face of a decomposing body].
AB  - The corpse of a 41-year-old medical doctor was found in his bed. The body was
      partially dried out; parts of the hip region were skeletonized due to maggot
      activity. In the facial region of the corpse, blowfly maggots (Lucilia
      (Phaenicia) sericata [Meigen]) were found exclusively in one eye socket. This is
      an unusual occurrence since on that side, a bedlight (40 W light bulb) had been
      burning during the seven week post mortem interval. All other lights in the
      apartment were switched off, and no direct sunlight could enter the space where
      the body was found (only a TV set had been running all the time, ca. 2 m away
      from the head at the foot end of the bed). Obviously, the maggots who usually
      flee light had used up the one eye that was further away from the bedlight as a
      feeding source. Since the continuing mummification of the corpse led to a
      substantial restriction of feeding material, the maggots finally switched to the
      eye that the light was shining on.

PMID- 11824100
TI  - [Analysis of the increasing role of laparoscopy in the management of acute
      abdomen in pregnancy].
AB  - This is a review of the epidemiological, diagnostic and therapeutic aspects of
      acute abdominal conditions during pregnancy. We emphasize the recent changes in
      surgical criteria that have appeared since the advent of laparoscopic surgery.
      The incidence of acute appendicitis during pregnancy is 1 in every 1,500 while
      approximately 4.5% of pregnant women have asymptomatic cholelithiasis and 0.05%
      acute cholecystitis. Up to 40% of these patients will require surgery during
      gestation and it is well known that abdominal interventions in this period carry
      out a higher risk of miscarriage or premature labor. We analyze the most common
      causes of acute abdomen during pregnancy as well as the special considerations of
      conservative treatment, open surgery and laparoscopic surgery. We also review the
      technical aspects of laparoscopic procedures and the safety guidelines by the
      Society of American Gastrointestinal Endoscopic Surgeons. It is concluded that
      the laparoscopic approach is safe and effective in the diagnosis and treatment of
      acute abdominal pathology during pregnancy. The advantages over conventional open
      surgery have made many surgeons and gynecologists change their criteria in favor
      of laparoscopy and this is now often their first choice of treatment.

PMID- 11824101
TI  - [Pregnancy rate in cryopreserved embryos based on the classical morphologic
      scoring and the integrity of blastomeres at thawing].
AB  - Two different thaw embryo classifications were evaluated, the morphologic classic
      evaluation (Veeck, 1990) and all blastomeres intact at the time of embryo
      transfer. We also discuss the clinic parameters and the physiopathological causes
      implicated in the successful of this treatment. 176 ovarian stimulation cycles
      and 513 cryopreserved embryos were reviewed. We found better pregnancy rate and
      delivery rate in embryo transfers were at least one embryo had all blastomeres
      intact compare with the transfers with good quality embryos (1+, 2+) of the
      morphologic classic evaluation without statistic significance (p > 0.05).
      Pregnancy and delivery rate were higher in cases with embryo in pronuclear stage
      compare with cleavage stage (p < 0.05). The blastomeric harm disturbs the embryo
      implantation phase and the future is oriented to the microsurgical remove of the
      damaged blastomeres and the use of assisted hatching.

PMID- 11824102
TI  - [Giant chorioangioma of the placenta: report of a case].
AB  - Chorioangioma of the placenta is a benign vascular growth most frequently. Many
      small neoplasms are missed in routine examination of the placenta. The large
      tumors cause problems for the clinical outcome of the pregnancy or delivery or
      for the infant. We report a giant chorioangioma of the placenta of ten
      centimeters diagnosed in delivery by cesarean section in women with gestation
      third without complications. The benign vascular growth to fetal surface of the
      placenta. The histological variety was an angioblastic. In this case complication
      maternal or infant were not diagnosed.

PMID- 11824103
TI  - [Hypogastric artery ligation. Safety and efficacy of a training program].
AB  - Bilateral hypogastric artery ligation is a technique described in the antiquity
      to restrain the hemorrhage in the gynecological and obstetric surgery. There are
      few Gineco-obstetricians that dominate the technique, for what intended a
      training program, in which was to demonstrate their security and effectiveness.
      We carry out a program where were qualified 14 gineco-obstetricians, theoretical
      and surgically. Results were analyzed finding an acceptable security with 1.5% of
      complications and an effectiveness demonstrated when having to the program 92.9%
      of students that reached the competition. We intend to reply the course in other
      hospital units, in order to decrease the maternal mortality for hemorrhage
      obstetric or gynecological.

PMID- 11824104
TI  - [Stomas in pregnancy, clinical case and review of the literature].
AB  - Stomas and pregnancy is an uncommon event and the literature in this regard is
      scarce, this poses significant concern on its management. Among the etiology we
      found the ulcerative colitis, trauma, and rectovaginal fistula, etc. The
      management should include a perinatologist and a specialist in colon and rectum.
      We should be familiarized with the potential complication as the intestinal
      obstruction, stoma prolapse, narrowing of the stoma and bleeding. The route
      delivery should be vaginal and the c-section is reserved for obstetric
      indications. The patient must receive education regarding stoma complications,
      and how to copy to live with a stoma.

PMID- 11824105
TI  - [Availability of condoms in Mexico City].
AB  - INTRODUCTION: At the beginning of 1999, Mexico occupied third place, after USA
      and Brazil, in the number of accumulated cases of AIDS (38,390 notified cases) in
      America. More than 80% of the cases corresponded to men between 20 and 44 years
      old. The transmission by sexual route has increased in both sexes, the proportion
      of men infected by sexual contact increased from 85% in 1991 to 90% in 1998 and
      in women this proportion increased from 41% in 1991 to 57% in 1998. The ratio
      male/female of cases of AIDS has varied from 17:1 in 1983 to 6:1 in 1998. Condom
      use is considered an effective method for the prevention of the transmission of
      STI's/HIV and therefore the availability is of paramount importance to promote
      use with the finality of combating these diseases. METHOD: A simple randomized
      sampling was done in 612 establishments that included: drugstore, bars and
      nightclubs, hotels and motels, self-service shops and health centers in Mexico
      City, where am cross sectional study was performed during June and July of 1995,
      to evaluate the availability of condoms considering three important items: a)
      percent per capita required to buy an annual endowment of 100 condoms in
      comparison with this same indicator reported in other countries; b) physical
      availability, on behalf of the Secretaria de Salud, Mexico City, that considers
      the volume of existing condoms to be utilized for a year by the public sector in
      this city; c) physical availability of condoms in different evaluated locations.
      RESULTS: In order to purchase an annual supply of condoms an individual needs the
      assign $500 (Pesos) which represents 2.3 to 2.6% of the annual GNP per capita for
      1998 and 1997 respectively. The physical availability of condoms, on behalf of
      the Secretaria de Salud, Mexico City, was 94.9% in health centers. In drugstores,
      hotels and motels, self-service shops, bars and nightclubs the availability of
      condoms was 100%, 82.9%, 75% and 1.2%, respectively. CONCLUSIONS: It has been
      documented that the adequate use of condom is an effective strategy for the
      prevention of STI's/HIV, therefore the availability of this method of prevention
      is important to decrease the incidence of these diseases The results of this
      study indicate that the price for this method of prevention represents an
      important expense for the homes, which is a limiting factor for condom use,
      especially for those populations that include adolescents and young adults. It
      then becomes necessary for Government Institutions to implement programs that
      will subsidize this method of prevention. Availability is less in self-service
      shops and practically non-existent in bars and nightclubs. It is suggested that
      the availability of condom should be mandatory in public places, like bars and
      nightclubs, where the risk to start casual sexual contact is eminent.

PMID- 11824106
TI  - [Changes in pancreatic arginase activity in pubertal and adult rats induced by
      castration].
AB  - Arginase activity in kidney, and small intestine in several mammalian species is
      sensitive to castration, a finding that could suggest their dependence on
      testosterone. However, as far as we know, information on regulation of pancreatic
      arginase activity is scarce. In this paper, the effect of orchidectomy on
      pancreatic arginase activity in pubescent and adult rats was studied. Male
      pubescent and adult rats, 21 days old and 4 months old, respectively, were
      orquidectomizades and sacrificed at various times post-surgery. Groups of intact
      rats served as controls. Arginase activity and proteins were measured in
      pancreatic tissue. The activity of this enzyme was measured in serum in addition
      to glucose, triglycerides and total proteins. In pubescent rats pancreatic and
      serum arginase activities peaked at day 5 post-surgery, increased arginase
      activity in adult rats was seen at day 20. Changes in serum and pancreatic
      proteins in pubescent, but not in adult, castrated rats were observed. Taken
      together, these results suggest that pancreatic arginase activity is androgen
      dependent and that there is age-difference, probably due lo distinct patterns of
      hormone secretion in pubescent and adult rats.

PMID- 11824107
TI  - [Prophylactic appendectomy with invagination during cesarean section].
AB  - OBJECTIVE: To evaluate the impact of the prophylactic appendectomy acComplished
      during cesarean section about postoperative morbidity. METHODS AND MATERIALS:
      Fifty-nine patients with pregnancy at term and had a cesarean section were
      randomized in two groups: Group I: Twenty-nine patients subjected to cesarean
      section as well as prophylactic appendectomy with invaginant technic and Group
      II: Thirty patients subjected just to cesarean section. The analyzed variables
      were: surgical time, hospitable stay and postoperative morbidity. RESULTS:
      Surgical time were similar between two groups (means: 56.75 min vs. 53.96 min to
      group I and II). The means of the hospitable stay was 29.98 hours (SD +/- I 1.81)
      and 27.72 hours (SD +/- 6.91) to Group I and II respectively, without significant
      differences statisTIcally between the groups. There were no postoperative
      morbidity in any group. CONCLUSIONS: Cesarean section plus prophylactic
      appendectomy with invaginant technic is an easy and safe procedure to be
      performed. It does not produce postoperative morbidity, besides it does not
      increase surgical time and hospitable stay.

PMID- 11824108
TI  - [Prediction of fetal wellbeing with Doppler flowmetric profile in pregnant
      hypertensive women].
AB  - In order to evaluate the diagnostic accuracy of the Doppler ultrasonography
      profile in the assessment of fetal wellbeing in hypertensive pregnancies, 171
      women at 36-42 week's gestation were included. A Doppler color ultrasound
      scanning was made and the score of the Doppler ultrasonography profile were
      correlated with the neonatal outcome, with one minute Apgar's score or admission
      to neonatal intensive care unit as main outcome. The Doppler ultrasonography
      profile includes: umbilical artery Doppler flow velocity waveforms, amniotic
      fluid volume, fetal movements, placental grading and fetal growth pattern. In 145
      cases (84.7%) had gestational hypertension without proteinuria, 22 patients
      (12.9%) had chronic hypertension and only in 4 cases (2.4%) preeclampsia was
      found. In 101 patients (59%) a cesarean section was made, 66 cases delivered
      normally and 4 (2.4%) patients had complicated vaginal delivery. Scores of
      diagnostic tests were: sensitivity 44%, specificity 99%, positive predictive
      value 80% and negative predictive value 97%, with an average accuracy of 71.5%.
      The multiple logistic regression analysis with 5 parameters of the Doppler
      ultrasonography profile had a determination coefficient (R2 = 0.15125) P < 0.01,
      and umbilical artery Doppler flow velocity waveforms had a regression coefficient
      -31.3959 (P < 0.05). It was concluded that the Doppler ultrasonography profile is
      a test with high predictive values in assessing fetal wellbeing in hypertensive
      pregnancies and the umbilical artery Doppler flow velocity alone is a significant
      variable in the multiple logistic regression analysis.

PMID- 11824109
TI  - [Lawsuits against gynecologists-obstetricians in the National Commission of
      Medical Arbitration].
AB  - The study of claims motives is relevant since Obstetrics and Gynecology (O&G) is
      one of the specialties that it is involved with greater frequency in demands in
      the Medical Arbitration National Commission (CONAMED). OBJECTIVE: In order to
      know the causes by those which the patients have attended to be complained of the
      attention provided by a Obstetrician/Gynecologist (OG). MATERIAL AND METHODS:
      Between June 1, 1996, and November 30, 1998, there were 635 demands reported to
      the CONAMED for obstetrical or gynecological care, 375 (60%) derived from
      obstetrical care; claims were grouped by motives and for stage of the attention
      in which they were originated. RESULTS: There were more than 17 different causes
      of claim, the most frequent were: complications (20%), care not opportune (16%),
      accidents (15%), improper actions (15%), diagnostic error (10%). Claims were
      derived from: Surgical procedures (45%), medical treatment (27%) and diagnosis
      (13%). 15 (2.4%) of claims were generated from vaginal delivery, but only 9
      (1.4%) were obstetrician related. Obstetric surgical procedures account for 23%
      of claims. CONCLUSIONS: OG are more claimed because work harder, more than one
      million vaginal and more than 500,000 cesarean deliveries are performed yearly in
      Mexico. The rates of reported claims are low, one per 10,000 deliveries attended;
      one per 275,000 vaginal deliveries, one per 8,400 obstetric surgical procedures.
      It all points OG claims as a probabilistic problem, risk related.

PMID- 11824110
TI  - Modeling the professionally successful practice.

PMID- 11824111
TI  - Identalloy: risk management tool and more.

PMID- 11824112
TI  - From "no way" to "know-how": getting through tough times with information
      management.

PMID- 11824113
TI  - Is this in the best interest of our patients?

PMID- 11824114
TI  - ReD hot hygiene, Part 3: D is for dynamic.

PMID- 11824115
TI  - Aesthetic treatment of devital teeth rebuilding strength and shade from within.

PMID- 11824116
TI  - Panoramic radiographic findings: case reports of ectopic teeth and antroliths
      within or adjacent to the maxillary sinus.

PMID- 11824117
TI  - Anterior retention with a reinforced composite resin splint after cosmetic
      orthodontic treatment.
AB  - Even in the most stable types of orthodontic treatment, any relapse at all may be
      unacceptable cosmetically. Through the placement of a reinforced composite
      splint, the teeth can be held in position and more significantly recontoured,
      thus augmenting the final result. Subsequent splint removal can be done
      incrementally 3 to 5 years after placement as the patient desires.

PMID- 11824118
TI  - Design and management of the worn anterior dentition: a case study with porcelain
      veneers and a ceromer/fiber-reinforced composite framework.

PMID- 11824119
TI  - The S.I.R. system: separated instrument retrieval using various-diameter, dead
      soft bonded tubes.

PMID- 11824121
TI  - Using plumber's teflon tape to enhance bonding procedures.

PMID- 11824120
TI  - Fractures: know your radiographic anatomy.

PMID- 11824122
TI  - Prevention: the key to successful nonsurgical periodontal treatment.

PMID- 11824123
TI  - The utilization of a preprosthetic extraoral verification stent for dental
      implant-supported reconstructions.

PMID- 11824125
TI  - Some help for literature study in anatomical variation reports.

PMID- 11824124
TI  - The bane of the baby boomer: coronal fracture syndrome.

PMID- 11824126
TI  - Use of the extensor retinaculum as a donor site for bone-ligament-bone grafts.
AB  - The recent introduction of bone-ligament-bone grafts for ligament reconstruction
      in hand surgery has led to a search for suitable graft donor sites. The extensor
      retinaculum had been suggested, but harvesting details were still lacking. We
      therefore studied the anatomy of the extensor retinaculum, with radiography and
      morphometric measurements. Ten cadaver wrists were dissected; the thick portion
      of the retinaculum and its insertions on the radius in the different extensor
      compartments were studied. The compartments were wire-marked, and AP radiographs
      taken of each specimen. The retinaculum spanning the first three compartments was
      removed with the bony ridges it inserted on, and the inter-ridge retinaculum
      length was measured. A comparison of our dissections with the radiographs showed
      that only the radial compartments 1, 2 and 3 had constant bony insertions on both
      ridges, making them suitable for bone-ligament-bone grafting. The mean
      compartment length was 11.7 mm (compartment 1), 17 mm (compartment 2) and 7.3 mm
      (compartment 3) respectively. Thus, the extensor retinaculum can be relied upon
      to provide bone-ligament-bone grafts from the first three compartments, for
      possible use in ligament reconstructions in the hand and wrist.

PMID- 11824128
TI  - Origin and make up of the human sural nerve.
AB  - The dissection of 37 cadavers has shown that in only a third of cases, the sural
      nerve comes from the communication between the medial cutaneous nerve, derived
      from the tibial nerve, and the communicating branch of the lateral cutaneous
      nerve of the leg which comes from the lateral popliteal nerve. The communication
      is most often at the junction between the proximal two-thirds and distal third of
      the leg, on average 2 mm below the transverse crease of the popliteal fossa. The
      medial cutaneous nerve was absent in only one case. On the other hand, in 11
      cases the lateral cutaneous nerve or its communicating branch was missing. In 12
      cases without any anastomoses, the route of the sural nerve was followed by the
      medial cutaneous nerve of the leg in 9 cases and by the lateral cutaneous nerve
      in 3 cases. The majority of branches to the proximal half of the calf came from
      the lateral cutaneous nerve. In the lower part of the leg, the sural nerve and/or
      the medial cutaneous nerve gave numerous branches to the Achilles' tendon and to
      the integuments of the lateral aspect of the heel and lateral malleolus.

PMID- 11824127
TI  - Functional anatomy of the medial ligamentous complex of the elbow. Its role in
      anterior posterior instability.
AB  - The question remains unanswered regarding the role of repair of medial ligament
      injuries associated with subluxation of the elbow and non-reconstructable radial
      head fracture and whether or not this will decrease the risk of chronic
      instability and cubitus valgus. The goal of this study was to define the role of
      the medial ligamentous complex of the elbow in elbow instability and to describe
      the anatomy of the complex in 35 fresh-frozen cadaver elbows. We documented
      medial ligamentous complex anatomy and compared our results to those in the
      literature. 25 elbows were dissected in order to describe the different bundles
      of the medial ligament complex and to precise the positions of the elbow that
      placed each in tension; section of the different ligamentous bundles was done to
      study the role of each in elbow stability. 10 other elbows were dissected and
      used for the ligamentous section studies which were performed subcutaneously. We
      found two bundles at the level of the anterior portion and termed them
      superficial and deep. Section of the anterior bundle lead to posterior
      subluxation of the elbow at 30-100 degrees flexion in both supination and
      pronation. Posterior subluxation was obtained after an anterior capsulotomy;
      medial epicondylectomy did not compromise the stability of the elbow after a
      complete section of the insertion of the deep fibers of the anterior bundle.
      Elements thus required for stability of the elbow are integrity of the articular
      surface of the humerus and the ulna, and the anterior bundle of the medial
      ligamentous complex.

PMID- 11824129
TI  - Capsular attachment to the distal radius for extracapsular placement of pins.
AB  - The aim of this study was to evaluate the anatomy of the wrist joint capsule on
      the distal radius. As such the extent of the joint capsule and the limits of
      attachment in relation to the articular surface were determined. Furthermore, the
      study also determined whether there was any reflection of the capsule onto the
      distal radius. Fifty cadaveric specimens, preserved according to Thiel's method,
      were assessed. After careful dissection the distance between the chondral line of
      the carpal articular surface and three defined points on each of the palmar and
      dorsal aspects of the radius were measured. In none of the specimens was there
      any variation in the course and extent of the joint capsule. Using external
      fixators for managing fractures of the distal radius, pins and wires can be
      placed subchondrally close to the articular capsule. The risk of intraarticular
      infection, due to pin tract infection in intraarticularly positioned pins, is
      very low.

PMID- 11824130
TI  - Lymphatic drainage of the pericardium to the mediastinal lymph nodes.
AB  - The lymphatic drainage of the pericardium may have a prognostic value in lung
      cancer and its anatomical pattern was the purpose of this study. The lymphatic
      vessels of the pericardium were visualized on 12 fresh adult human cadavers by
      injection of a green colorant by means of the classical equipment for pedal
      lymphography. Seventeen injections were performed on the right side and 22
      injections on the left side, visualizing 20 and 29 lymphatic pathways
      respectively. Whatever the side injected, the lymphatic vessels mainly directed
      toward the tracheobronchial nodes (n = 35) and less frequently toward the
      prepericardial lymphatic vessels and nodes (n = 14). Such results demonstrate the
      aggravating role played by the lymphatic drainage in the prognosis of the lung
      cancers invading the pericardium.

PMID- 11824131
TI  - Ocular and periorbital anthropometric measurements in term Turkish newborns.
AB  - This study was conducted in an effort to determine the normal landmarks in the
      eyelids and eyebrows of newborns and the relationships between them. We also
      correlated all measurements with gender and head circumferences. The
      anthropometric measurements were performed on 86 normal term newborns (40 males
      and 46 females) in the first 48 hours after delivery. There was no significant
      difference between either sex, or between the right and left eyes. In contrast, a
      statistically significant positive correlation was found between the head
      circumference and the horizontal fissure length (r = 0.42, p < 0.01). In
      addition, a significant correlation was found between the upper eyelid crease
      distance and the horizontal and the vertical fissure lengths (r = 0.27, p < 0.01;
      r = 0.22, p < 0.05, respectively). The results indicate that the normal eyelid
      crease location may be used as a landmark for guidance to plan surgical and
      reconstructive procedures.

PMID- 11824133
TI  - The canal of the posterior ampullar nerve: an important anatomic landmark in the
      posterior fossa transmeatal approach.
AB  - The canal of the posterior ampullar nerve is located between the inferior part of
      the internal acoustic meatus and ampulla of the posterior semicircular canal. It
      permits a more accurate localisation of the underlying labyrinth in inner-ear
      surgery. An anatomical and radiological study was undertaken to determine the
      importance the relationship between the canal and the labyrinth. Ten dry and 10
      cadaveric temporal bone dissections, together with 20 high resolution CT scans of
      the same temporal bones were studied in an attempt to describe the anatomy of the
      canal of the posterior ampullar nerve. The length of the canal of the posterior
      ampullar nerve, the length of internal acoustic meatus, and distances from porus
      acusticus to the singular foramen and the transverse crest, and from the singular
      foramen to the vestibule and transverse crest, and from operculum to the sigmoid
      sinus and to the porus acusticus were measured. During the transmeatal posterior
      cranial fossa approach using the canal of the posterior ampullar nerve as a
      landmark enables more bone to be safely removed from the internal acoustic meatus
      thus preserving hearing.

PMID- 11824132
TI  - The lateral inframalleolar fat pad: a poorly recognized anatomical structure.
AB  - The authors carried out an anatomical histological study of the lateral
      inframalleolar region in order to improve knowledge of a fat pad of the lateral
      aspect of the ankle which is not mentioned in most anatomical texts. Twenty-four
      ankles, from 12 cadavers, free of any local pathology or malformation, were
      studied. Twenty ankles were dissected, of which, five had samples taken for
      histological examination. Colored latex was injected into the joint cavities of
      the last four ankles before anatomical cuts were made in three planes. This study
      allowed the description of the fat pad which we have called the lateral
      inframalleolar fat pad (LIMFP). It is oval and made up of a classical unilocular
      fatty tissue which is clearly distinct from the subcutaneous plane. We have
      defined its relationships and in particular, the neurovascular ones. The sural
      nerve which supplies cutaneous sensation to part of the 5th toe runs over the
      surface of the fat pad. It is accompanied on this part of its course by the short
      saphenous vein which gives off a medial perforator which traverses the LIMFP.
      Because of these neurovascular relationships, the LIMFP may play a role in the
      pathophysiology of neuralgias of the lateral aspect of the 5th toe or of the 4th
      digital interspace. It should be recognized before any operations on the lower
      limbs, in particular, before any plastic surgical liposuction, in order to
      optimize the resection volume to prevent inaesthetic over correction or under
      corrections which are often confused with residual edema.

PMID- 11824134
TI  - A prospective radiological anatomical study of the variations of the position of
      the colon in the left pararenal space.
AB  - Percutaneous puncture of the kidney allows direct access to the pyelocalicial
      cavities. The posterior approach of this retroperitoneal organ can be complicated
      of transcolic punctures due to the postrenal position of the colon. A prospective
      radiological anatomical study of the relationship between the left kidney and the
      descending colon was undertaken. One hundred computed tomograms of adult subjects
      were obtained from which the anatomy of the left perirenal area was determined:
      the descending colon is more frequently behind the kidney in the young females.
      Two main factors determinants of this situation are: 1) colon ontogenesis in
      relation to the attachment of the primitive mesocolon, permitting a 'fixed' left
      colon, or 'moving' left colon at the end of a long mesocolon, allowing it to pass
      behind the kidney; 2) a mechanical factor whereby the accumulation of perirenal
      fat with increasing age may be a limiting factor in lateral displacement of the
      colon.

PMID- 11824135
TI  - The axillopectoral muscle (of Langer): report of three cases.
AB  - The axillopectoral muscle, usually called Langer's axillary arch instead of
      Langer's arm arch, is a supernumerary muscle and is the principal anatomic
      variation of the axilla. Three cases of the muscle were observed originating from
      latissimus dorsi crossing over the axillary neurovascular bundle and inserting
      deep to the insertion of pectoralis major or into the coracoid process.
      Clinicians should be aware of its existence as it can give rise to different
      pathologies. It should be recognised and excised to expose the axillary artery
      and vein in patients with trauma and to perform axillary lymphadenectomy or
      axillary bypass. It should be considered in the differential diagnosis of
      axillary masses or in a history of intermittent axillary vein obstruction. If the
      muscle causes problems its excision should be curative.

PMID- 11824136
TI  - Hypoplasia of the left lobe of the liver.
AB  - In a forensic autopsy, hypoplasia of the left lobe (lateral segment) of the liver
      was found. Although the cause was unknown, the morphologic anomaly observed in
      this case was regarded as congenital because there was no history of surgery.
      Moreover, the main vessels of the left lobe were present despite complete absence
      of the parenchyma.

PMID- 11824137
TI  - Aortic origin of right hepatic artery and superior mesenteric origin of splenic
      artery: two rare variations demonstrated angiographically.
AB  - Anatomical variations of the celiac trunk and superior mesenteric artery are not
      infrequent. Knowledge of the existing aberrations is important in planning and
      conducting surgical or radiological procedures. A case of right hepatic artery
      arising independently from the aorta supplying an hepatocellular carcinoma was
      identified, through which transarterial chemoembolization was successfully
      performed. A second case is presented with a common splenomesenteric trunk
      branching into the splenic and superior mesenteric arteries. These two cases
      represent exceptional arterial variations in the upper abdomen.

PMID- 11824138
TI  - Duplication of the parotid duct: a previously unreported anomaly.
AB  - A hitherto unreported duplication of the parotid duct in a 63-year-old man is
      reported. The ducts were found in the right cheek during cadaver dissection. The
      surrounding connective tissue of the ducts was removed and a photograph was
      taken. These two parotid ducts were then removed and fixed in a 10% formalin
      solution, embedded in paraffin blocks and the sections stained with hematoxylin
      eosin. The histologic findings showed that both had the normal ductal columnar
      epithelium. There was only one parotid duct in the left cheek.

PMID- 11824140
TI  - A rare human variation: a major branch of the ulnar artery found in the carpal
      tunnel.
AB  - During a routine anatomic dissection of a 60-year-old female cadaver, a large
      branch of the ulnar artery in the carpal tunnel was found in the left forearm.
      This branch crossed the median nerve anteriorly. Guyon's canal contained another
      branch of the ulnar artery and the ulnar nerve. There was no superficial palmar
      arch in the left hand. The right forearm was without any vascular anomalies. This
      anomaly has considerable consequences for surgeons considering endoscopic carpal
      release, because there is a significant risk of injury to the ulnar artery
      branch.

PMID- 11824139
TI  - Absence of the portal bifurcation at the hilum of the liver due to intrahepatic
      origin of the left branch of the portal vein.
AB  - The authors report a rare anomaly of portal vascularization which was detected by
      CT-scan and MRI and then confirmed surgically. There was no portal bifurcation at
      the hilum of the liver. After giving off its right dorsal branch, the portal vein
      entered the right liver and divided in the parenchyma into the right ventral and
      left branches. The arteriobiliary distribution was normal. Only a few similar
      cases have been reported. The left branch of the portal vein is reported to have
      few variations in contrast with the right one, which has many. The venous
      structure of the liver varies increasingly with the distance from the left
      umbilical vein. During a right hepatectomy, the possibility of such a
      vascularization makes it necessary to ensure that the left branch of the portal
      vein starts upstream before dividing a portal branch entering the right liver.

PMID- 11824141
TI  - [The importance of tuning forks].
AB  - Turning fork tests are used routinely by many otologists. A different group of
      otologists find the tests inconsistent and unreliable. This controversy has
      probably developed because the audiometer has replaced the tuning fork in hearing
      measurement. Some principles of the Weber- and Rinne-tuning fork test are shortly
      described. The necessary control of pure tone audiometry by tuning forks is
      pointed out. The value particularly in the diagnosis of conductive hearing loss,
      and the tuning fork's limitations are discussed.

PMID- 11824142
TI  - [Treatment of acne with consequences -- pseudotumor cerebri due to
      hypervitaminosis A].
AB  - Pseudotumor cerebri (PTC) is an entity characterized by elevated intracranial
      pressure of probably multifactoral origin, but most cases remain idiopathic. We
      report a 15-year-old girl with PTC due to prolonged consumption of Arovit
      (Vitamin A) for treatment of acne. The diagnosis was established by measuring
      raised cerebrospinal fluid pressure after an intracranial mass lesion and dural
      venous sinsus thrombosis were excluded. The increased level of vitamin A
      confirmed the diagnosis of hypervitaminosis A as the causative pathogen. The
      patient was treated with lumbar punctures and acetazolamide (Diamox). PTC due to
      hypervitaminosis A is a serious complication, which can cause permanent visual
      impairment. Patients treated with retinoids require proper surveillance. The
      elevated serum level of retinoids after withdrawal may persist for weeks.

PMID- 11824144
TI  - [Clarification in probable coagulation disorder].

PMID- 11824143
TI  - [A 50-year old patient with macroprolactinoma].

PMID- 11824145
TI  - [Anterior cruciate ligament rupture in athletes -- surgical or conservative
      therapy?].

PMID- 11824147
TI  - Breast cancer update.

PMID- 11824146
TI  - [Safety aspects of folic acid for the general population].
AB  - Periconceptional use of folic acid reduces the risk of neural tube defects
      considerably. In Switzerland, implementation of these findings could be improved
      through fortification of a staple food with folic acid. The present paper reviews
      possible hazards associated with high intake of folic acid in the general
      population. Among the potential safety issues are interaction between folic acid
      and zinc, interaction between folic acid and drugs (phenytoin, methotrexate etc.)
      and hypersensitivity to folic acid. Of main concern are adverse effects of folic
      acid in cobalamin deficiency. Solutions are discussed.

PMID- 11824148
TI  - Screening for colorectal cancer in Rhode Island.

PMID- 11824149
TI  - Childhood cancer: past successes, future directions.

PMID- 11824150
TI  - Demented politicians.

PMID- 11824151
TI  - Brain tumors.

PMID- 11824152
TI  - Some comments on a possible ancestor.

PMID- 11824153
TI  - Prevention and treatment recommendations for community acquired pneumonia.

PMID- 11824154
TI  - Rhode Island Hispanics have mainstream cancer rates.

PMID- 11824155
TI  - The Rhode Island Cancer Council.

PMID- 11824156
TI  - Medical lexicon: nausea and vomiting.

PMID- 11824157
TI  - Cancer in the new millennium.

PMID- 11824158
TI  - Update in non-small cell lung cancer.

PMID- 11824159
TI  - [Atrial fibrillation successfully converted. A new standard in the prevention of
      recurrence?].

PMID- 11824161
TI  - [Drug interactions in the practice. Which combinations are taboo?].

PMID- 11824160
TI  - [Chronic liver diseases. The nihilism has gone].

PMID- 11824162
TI  - [Drug therapy in the old age. Drug effects in the elderly].
AB  - The frequency of multimorbidity in elderly patients may mislead the physician
      into practicing polypragmasy (polypharmacy), resulting in unpredictable drug
      interactions. Such interactions are a quite common cause of hospitalization in
      geriatric patients. Pharmacokinetics are often altered in the aged, and
      individualized medication should take into consideration not only the patient's
      age, liver and kidney function, but also the individual variability of hepatic
      metabolism and drug absorption from the gastrointestinal tract dictated by
      genetic polymorphism. Drug treatment in the elderly should always be carefully
      assessed as to its risks and benefits, and, where indicated, certain medications
      should be replaced by or omitted.

PMID- 11824163
TI  - [Unexpected high plasma level of drugs. Blocked transporter can be the cause].

PMID- 11824164
TI  - [Small-volume-resuscitation: a new therapy concept. Faster volume replenishment
      for trauma patients].

PMID- 11824165
TI  - [Alzheimer dementia. Comparison of the effectiveness of cholinesterase inhibitors
      and gingko].

PMID- 11824166
TI  - [To differentiate Alzheimer's and vascular dementia? Today no longer up to date].

PMID- 11824167
TI  - [Alzheimer patients. To treat with anti-dementia drugs in spite of unanswered
      questions].

PMID- 11824168
TI  - [Disease management program. "Managed Care": individual medicine on the outside].

PMID- 11824169
TI  - [Antibiotics in respiratory tract infections. Enormous differences in
      compliance].

PMID- 11824170
TI  - [Chronic bronchitis. When to use antibiotics?].

PMID- 11824171
TI  - [Innovation, step innovation, Me too. Are calcium antagonists interchangeable?].

PMID- 11824172
TI  - Hypocalcemia in children: pathogenesis and management.
AB  - Hypocalcemia can be devastating if unrecognized. Neuromuscular dysfunction occurs
      in severe cases. A review and an update on the topic may assist general
      pediatricians. The authors provide a general overview of pathogenesis and
      management of hypocalcemia in children.

PMID- 11824173
TI  - Antipyretic effects of dipyrone versus ibuprofen versus acetaminophen in
      children: results of a multinational, randomized, modified double-blind study.
AB  - This study compared the antipyretic effectiveness of acetaminophen, ibuprofen,
      and dipyrone in young children with fever. The results were based on a modified
      double-blind, randomized, multinational trial that evaluated 628 febrile
      children, aged 6 months to 6 years. All three drugs lowered temperature in the
      555 patients completing the study. Temperature normalization rates in the
      ibuprofen and dipyrone groups (78% and 82%, respectively) were significantly
      higher than the acetaminophen group (68%, P = 0.004). After 4 to 6 hours, mean
      temperature in the dipyrone group was significantly lower than the other groups,
      demonstrating longer temperature normalization with dipyrone. All three drugs
      showed comparable tolerability profiles.

PMID- 11824174
TI  - Are we losing good drugs?

PMID- 11824175
TI  - A double-blind, placebo-controlled crossover study investigating the effect of
      porcine secretin in children with autism.
AB  - OBJECTIVES: A recent patient series reported the incidental findings of improved
      social and language skills in 3 children with autistic spectrum disorders after
      the administration of secretin, a peptide hormone. However, a subsequent study
      did not find evidence for a drug effect. Parents are seeking treatment with
      secretin despite the absence of empirical investigations demonstrating
      amelioration in autism symptomology. In order to more precisely measure the
      effects of secretin, this study investigated the effect of a single intravenous
      dose of porcine secretin on 12 autistic children through a randomized, double
      blind, placebo-controlled, crossover study. Children were assessed on objective
      language and on social, neuropsychological, and gastrointestinal measures to
      evaluate drug effects. The study was conducted over a 16-week trial. The results
      indicated that significant differences were not observed on the majority of the
      dependent variables. Statistically significant differences were observed on
      measures of positive affect and activity level following secretin infusion. In
      general, the autistic children did not demonstrate the improvements described in
      the initial retrospective report.

PMID- 11824176
TI  - Ear temperature measurements in healthy children using the arterial heat balance
      method.
AB  - This study was undertaken to determine the upper limit of normal ear
      temperatures, defined as the 95th percentile for infants, children, and
      adolescents, using the arterial heat balance method for measuring ear
      temperatures. Ear temperatures were measured in 62 infants, 0-2 months of age;
      346 children, 3-47 months; 226 children, 48-119 months; and 172 adolescents, 120
      227 months using the LighTouch Pedi-Q (Exergen Corp, Watertown, MA) ear
      thermometer. The 95th percentiles for the four age groups were 100.1 degrees F
      (37.8 degrees C), 100.3 degrees F (37.9 degrees C), 99.8 degrees F (37.7 degrees
      C), and 99.8 degrees F (37.7 degrees C), respectively. Temperatures above 100.0
      degrees F (37.8 degrees C) using the LighTouch Pedi-Q ear thermometer should be
      considered elevated.

PMID- 11824177
TI  - Externalizing behaviors and television viewing in children of low-income minority
      parents.
AB  - The parents of 151 children, ages 4-16 years, attending the pediatric outpatient
      clinic of an urban hospital were surveyed to determine if aggressive behavior
      among children of low literacy and low-income parents is related to excessive
      television viewing or to sociological variables such as ethnicity/race,
      education, occupation, and parents' marital status. The survey consisted of 22
      questions about the ethnicity, marital status, education, and occupation of the
      parent, the television viewing behavior of the child, and the externalizing
      behavior scale of the Child Behavior Checklist of Achenbach (CBC). The television
      viewing habits of children in this study were not significantly different from
      viewing habits reported in national surveys of the US population. T scores in the
      aggression scale of CBC were unrelated to the hours of television watched by
      children and the control of viewing by the parent but were significantly
      associated with the employment and marital status of the mother. Children of
      unemployed and single mothers had higher externalizing-behavior scores,
      suggesting that family ecological variables may have more influence on children's
      behavior than the duration of television viewing.

PMID- 11824178
TI  - Arterial disease causing refusal to walk in a toddler.

PMID- 11824179
TI  - Spontaneous adrenal hemorrhage associated with transient antiphospholipid
      antibody in a child.

PMID- 11824180
TI  - Delayed papilledema and hydrocephalus associated with shaking impact syndrome.

PMID- 11824181
TI  - Acute autoimmune hemolytic anemia following DTP vaccination: report of a fatal
      case and review of the literature.

PMID- 11824182
TI  - Congenital midline cervical cleft.

PMID- 11824183
TI  - Gastric duplication with extralobar pulmonary sequestration: an uncommon cause of
      "colic".

PMID- 11824184
TI  - Basic principles of synaptic physiology illustrated by a computer model.
AB  - A computer model is described that simulates many basic aspects of chemical
      synapse physiology. The model consists of two displays, the first being a
      pictorial diagram of the anatomical connections between two presynaptic neurons
      and one postsynaptic neuron. Either or both of the presynaptic cells can be
      stimulated from a control panel with variable control of the number of pulses and
      firing rate; the resulting presynaptic action potentials are animated. The second
      display plots the membrane potential of the postsynaptic cell versus time
      following presynaptic stimulation. The model accurately simulates temporal and
      spatial summation when the presynaptic cells are arranged and stimulated in
      parallel and simulates presynaptic inhibition when they are arranged and
      stimulated in series. Excitatory and inhibitory postsynaptic potentials can be
      demonstrated by altering the nature of the ionic conductance change occurring on
      the postsynaptic cell. The effects on summation of changing length constant or
      time constant of the postsynaptic cell can also be illustrated. The model is
      useful for teaching these concepts to medical, graduate, or undergraduate
      students and can also be used as a self-directed computer laboratory exercise. It
      is available for free download from the internet.

PMID- 11824185
TI  - Sleep as a teaching tool for integrating respiratory physiology and motor
      control.
AB  - Sleep exerts major effects on most fundamental homeostatic mechanisms. Current
      data suggest, however, that students of physiology and medicine typically receive
      little or no formal teaching in sleep. Because sleep takes up a significant
      component of our life span, it is proposed that current teaching in systems and
      integrative physiology is not representative if it is confined to functions
      describing wakefulness only. We propose that sleep can be readily integrated into
      various components of physiology and medical curricula simply by emphasizing how
      commonly taught physiological processes are importantly affected by sleep
      mechanisms. In our experience, this approach can be used to reinforce basic
      physiological principles while simultaneously introducing sleep physiology into
      the students' training. We find that students have a general and inherent
      interest in sleep and related clinical disorders, and this proves useful as an
      effective means to teach the material. In this paper, examples of how sleep
      influences motor control and the respiratory system will illustrate these points.
      These considerations also highlight some important gaps in traditional teaching
      of respiratory physiology.

PMID- 11824186
TI  - An inquiry-based learning model for an exercise physiology laboratory course.
AB  - We developed an inquiry-based learning model to better stimulate undergraduate
      students' cognitive development of exercise physiology laboratory concepts. The
      course core is the two independent research projects that students, working in
      small groups, complete during the last 9 wk of the semester. Student groups
      develop their own research question and hypothesis, design the experiment,
      collect and analyze the data, and report their findings to the rest of the class
      using presentation software. To help with success of the research projects,
      students are taken through a series of guided-inquiry laboratory activities
      during the initial 6 wk of the semester to develop laboratory skills and an
      understanding of the scientific process. Observations of student behaviors
      reflected a high level of enthusiasm and engagement in laboratory activities.
      Surveys, journal entries, and interviews indicated that students felt empowered
      by having ownership in their projects, which may be the key reason for the
      success of this model.

PMID- 11824187
TI  - Are current textbooks good enough for physiology education? For example, the ECL
      cells are missing.
AB  - Current textbooks are believed to provide an updated knowledge. Medical students
      usually read the textbooks but not the literature that contain the original
      research articles and reviews. Here, we examined the gap between the current
      textbooks and literature with the enterochromaffin-like (ECL) cells as an
      example. A total of 70 textbooks that were published for medical education during
      the last 10 yr was examined. The literature has been searched mainly from the
      Internet. We found that most textbooks (59 of 70) fail to mention the ECL cells.
      Due to the lack of information on the ECL cells, the mechanisms behind gastric
      acid secretion are described variously from book to book. However, up to the year
      2000, 574 research articles and reviews have been published on the various
      aspects of the ECL cells. The role of the ECL cells in the regulation of the acid
      secretion has been well demonstrated for more than 20 years. The fact that the
      textbooks are out of date cannot be explained by the time required to write and
      publish them. Therefore, we question whether or not the current textbooks are
      good enough for physiology education and suggest both teachers and students read
      not only the textbooks, but also utilize the other sources such as the Internet
      to find and fill the gaps between the textbooks and literature. This is one of
      the approaches of problem-based learning.

PMID- 11824188
TI  - Active learning of respiratory physiology improves performance on respiratory
      physiology examinations.
AB  - Active involvement in the learning process has been suggested to enhance creative
      thinking, judgement, interpretation, and problem-solving skills. Therefore,
      educators are encouraged to create an active-learning environment by
      incorporating active-learning strategies into the class. However, there is very
      little documentation of the effectiveness of active-learning strategies.
      Furthermore, faculty are often reluctant to incorporate new strategies without
      documentation of the effectiveness of these strategies. To address this concern,
      we compared the performance of two individual classes on an identical respiratory
      physiology examination. One class was taught respiratory physiology using active
      learning strategies. The other class was taught respiratory physiology using the
      traditional lecture format. The results document that students who learned using
      active-learning strategies did significantly better (P < 0.05) on the respiratory
      physiology examination than students who learned by the traditional lecture
      format (61 +/- 2.2 vs. 86 +/- 1.0). Thus, by actively involving students in the
      learning process, academic performance is enhanced.

PMID- 11824189
TI  - Determinants of cardiac function: simulation of a dynamic cardiac pump for
      physiology instruction.
AB  - A computer model is described that simulates the cardiac cycle of a mammalian
      heart. The model emphasizes the pressure-volume plot as a teaching tool to
      explain the behavior of the heart as a pump. It exhibits realistic responses to
      changes in preload, afterload, contractility, and heart rate while displaying
      time-dependent changes in pressure and volume in addition to the pressure versus
      volume plot. It differs from previous models by graphing these parameters on a
      beat-to-beat basis, allowing visualization of the dynamic adaptation of the
      pumping heart to various stimuli. A system diagram is also included to further
      promote student understanding of the physiology of cardiac function. The model is
      useful for teaching this topic to medical, graduate, or undergraduate students.
      It may also be used as a self-directed computer laboratory exercise.

PMID- 11824190
TI  - The effects of discovery learning in a lower-division biology course.
AB  - This study investigated discovery learning pedagogy and its effects on students'
      achievement and attitudes toward instruction in a lower-division biology course,
      entitled Structure and Function of Organisms. Instruction was primarily lecture
      based but included four discovery learning activities. Results indicate that
      students had greater achievement on content learned through discovery methods
      than lecture-based instruction. Findings regarding students' attitudes toward
      discovery-based instruction suggest that students enjoyed active, discovery-based
      problems, believed that discovery helped them gain an understanding of the
      material and helped them to develop skills that could be used in other courses.
      The study presented here shows that a moderate amount of discovery learning used
      in combination with traditional methods of instruction may be an effective means
      for promoting students' achievement.

PMID- 11824191
TI  - The Claude Bernard Distinguished Lecture. In pursuit of meaningful learning.
AB  - The Bernard Distinguished Lecturers are individuals who have a history of
      experience and expertise in teaching that impacts multiple levels of health
      science education. Dr. Joel Michael more than meets these criteria. Joel earned a
      BS in biology from CalTech and a PhD in physiology from MIT following which he
      vigorously pursued his fascination with the mammalian central nervous system
      under continuous National Institutes of Health funding for a 15-yr period. At the
      same time, he became increasingly involved in teaching physiology, with the
      computer being his bridge between laboratory science and classroom teaching. Soon
      after incorporating computers into his laboratory, he began developing computer
      based learning resources for his students. Observing students using these
      resources to solve problems led to an interest in the learning process itself.
      This in turn led to a research and development program, funded by the Office of
      Naval Research (ONR), that applied artificial intelligence to develop smart
      computer tutors. The impact of problem solving on student learning became the
      defining theme of National Science Foundation (NSF)-supported research in health
      science education that gradually moved all of Dr. Michael's academic efforts from
      neurophysiology to physiology education by the early 1980's. More recently, Joel
      has been instrumental in developing and maintaining the Physiology Education
      Research Consortium, a group of physiology teachers from around the nation who
      collaborate on diverse projects designed to enhance learning of the life
      sciences. In addition to research in education and learning science, Dr. Michael
      has devoted much of his time to helping physiology teachers adopt modern
      approaches to helping students learn. He has organized and presented faculty
      development workshops at many national and international venues. The topics for
      these workshops have included computer-based education, active learning, problem
      based learning, and the use of general models in teaching physiology.

PMID- 11824192
TI  - Models of venous admixture.
AB  - Medical students, residents, and allied health professionals often have
      difficulty quantitating ventilation-perfusion mismatch in ill patients. This
      manuscript quantitates ventilation-perfusion mismatch using the underlying
      physiological concepts and equations that describe mismatch. In addition,
      clinical problems with diagrams and worked-out solutions are supplied to help
      students master these equations as well as their practical limitations.

PMID- 11824193
TI  - Teaching peer review and the process of scientific writing.
AB  - Many undergraduate and graduate students understand neither the process of
      scientific writing nor the significance of peer review. In response, some
      instructors have created writing assignments that teach or mimic parts of the
      scientific publishing process. However, none fully reproduced peer review and
      revision of papers together with the writing and publishing process from research
      to final, accepted draft. In addition, most have been instituted at the graduate
      rather than undergraduate level. We present a detailed method for teaching
      undergraduate students the full scientific publishing process, including
      anonymous peer review, during the process of writing a "term paper." The result
      is a review article in the format for submission to a major scientific journal.
      This method has been implemented in the course Cell and Molecular Biology for
      Engineers at the University of Virginia. Use of this method resulted in improved
      grades, much higher quality in the final manuscript, greater objectivity in
      grading, and improved understanding of the importance of peer review.

PMID- 11824194
TI  - Simple techniques suitable for student use to record action potentials from the
      frog heart.
AB  - Demonstrating action potentials during class experiments is very educational for
      science students. It is not easy, however, to obtain a stable intracellular
      recording of action potentials from the conventionally used skeletal muscle
      cells, because the tip of a glass microelectrode often comes out or breaks due to
      muscle contraction. Here, I present a much simpler recording method using a
      flexible polyethylene electrode with a wide orifice (approximately 1 mm) for a
      bullfrog heart beating on automaticity. Extracellular recordings of action
      potentials (electrocardiogram) can be obtained by placing an electrode on the
      cardiac surface, and transmembrane potentials can be obtained by rupturing the
      membrane with negative pressure, i.e., whole cell configuration. Once attached to
      the heart by suction, the polyethylene electrode does not easily come off during
      contraction of the heart. Perfusion of the heart via the postcaval vein offers us
      opportunities for observing the effects of either changing ionic compositions of
      solutions or applying drugs. The techniques shown here provide a simple and
      convenient way to perform a variety of class experiments.

PMID- 11824196
TI  - Ethics, revisited.

PMID- 11824195
TI  - Is the water-tower analogy justified?

PMID- 11824197
TI  - Advances in the electronic era.

PMID- 11824198
TI  - Linking cardiovascular theory to practice in an undergraduate medical curriculum.
AB  - Case-based teaching (CBT) tutorials were introduced by the Physiology Department
      at Adelaide University to bridge the gap between theory and practice in the early
      years of undergraduate medical education. With the use of a clinical case-based
      environment, CBT aimed to achieve integration of structure-function relationships
      and an increase in students' capacity to apply a physiological understanding to
      clinical observations/symptoms and data. With peer-peer interactions in small
      groups, students could trial history taking and examination skills, interpret
      common investigations, and relate their findings to an understanding of structure
      and function. Here, the cardiovascular tutorials highlight the centrality of an
      understanding of structure and function in the evaluation of a case of syncope.
      An independent evaluation of the students' learning experience demonstrated that
      CBT tutorials were successful in their aims. The "hands-on" experience was highly
      rated, with students reporting that the CBT approach gave relevance to structure
      and function. Whatever the curriculum learning style, underpinning practice with
      an understanding of theory remains a desirable feature of medical education.

PMID- 11824199
TI  - Evaluating the impact of physical renovation, computerization, and use of an
      inquiry approach in an undergraduate, allied health human anatomy and physiology
      lab.
AB  - This paper describes and evaluates a major renovation of a human anatomy and
      physiology lab for allied health students. A Howard Hughes Medical Institute
      award funded an extensive collaboration between faculty involved in teaching the
      course and faculty with expertise in industrial and furniture design. The
      resulting physical lab has unique features designed to improve work in groups,
      student movement, and integration of computers with wet laboratories. The anatomy
      curriculum was switched from fetal pig dissections to the use of human cadavers,
      computer animations, and plastic models. An inquiry approach was integrated into
      the physiology curriculum. Student attitude surveys suggest that the physical and
      curricular changes resulted in a significant increase in student learning. An
      experiment designed to specifically test the effect of new vs. old equipment did
      not support a benefit to new equipment independent of changes in the lab physical
      environment and curriculum. Because the improvements in student attitude surveys
      occurred in the physiology but not the anatomy labs, we suggest that at least a
      portion of the increase is due to the institution of the inquiry approach.

PMID- 11824200
TI  - Endocrine refresher course 2001: modern medical curricula.

PMID- 11824201
TI  - Endocrinology concepts for medical students.

PMID- 11824202
TI  - Problem-based learning within endocrine physiology lectures.
AB  - Methods were needed to improve the interest of medical students in the 10-lecture
      Endocrine Physiology block at the end of the second semester of study. Other
      incentives for improvement included the possibility of attracting students into
      endocrine research electives and the pressure to improve teaching approaches that
      results from the high tuition they pay. The principal approach adopted was that
      of whole class problem-based learning sessions (PBLS) in which the lecture period
      begins with a brief overview of one to three simplified cases, followed by the
      usual didactic lecture. At the end of the lecture, each PBL case is read in
      detail, with several questions posed to the students. Their answers are then used
      to reinforce concepts from the lecture material. This method can also provide
      some continuity between lectures, either by using a case in several lectures to
      illustrate different points, or by posing a question at the beginning of class
      that illustrates a point from the prior lecture. The outcome of this approach has
      been very successful: student evaluations of the lecture block and their
      attendance have significantly improved.

PMID- 11824203
TI  - Multiple-format sessions for teaching endocrine physiology.
AB  - The University of Kentucky medical curriculum was revised in 1994 to implement a
      more interactive approach. The Endocrine Physiology section of the new physiology
      course, Human Function, was modified from its former daily lecture and weekly
      laboratory format to eight daily 3 1/2-h sessions. Each session is composed of
      four components: a didactic lecture, a whole class discussion session, a quiz,
      and a patient presentation. These components are presented in a staggered format
      over the course of 2 days, i.e., the lecture is presented on the first day, and
      the remaining three components take place on the second day. This allows students
      to assimilate the new lecture material before participating in the discussion
      session, quiz, and patient presentation, which are more interactive. This format
      has been received favorably by the students because of its variety, and it is
      easier to keep up with the material.

PMID- 11824204
TI  - Integration of neuroscience and endocrinology in hybrid PBL curriculum.
AB  - At the University of Missouri-Columbia, the medical school employs a problem
      based learning curriculum that began in 1993. Since the curriculum was changed,
      student performance on step 1 of the United States Medical Licensing Examination
      has significantly increased from slightly below the national average to almost
      one-half a standard deviation above the national mean. In the first and second
      years, classes for students are organized in classes or blocks that are 8 wk
      long, followed by 1 wk for evaluation. Initially, basic science endocrinology was
      taught in the fourth block of the first year with immunology and molecular
      biology. Student and faculty evaluations of the curriculum indicated that
      endocrinology did not integrate well with the rest of the material taught in that
      block. To address these issues, basic science endocrinology was moved into
      another block with neurosciences. We integrate endocrinology with neurosciences
      by using the hypothalamus and its role in neuroendocrinology as a springboard for
      endocrinology. This is accomplished by using clinical cases with clear
      neuroscience and endocrinology aspects such as Cushing's disease and multiple
      endocrine neoplastic syndrome type 1.

PMID- 11824205
TI  - Endocrine physiology in a patient-centered learning curriculum.
AB  - The medical curriculum at the University of North Dakota School of Medicine and
      Health Sciences has recently been redesigned into a problem-based/traditional
      hybrid model that utilizes an integrated organ systems-based approach to teach
      basic and clinical sciences. The number of lecture hours in general has been
      greatly reduced, and, in particular, lecture hours in physiology have been
      reduced by 65%. Students learn basic science in small groups led by a faculty
      facilitator, and students are responsible for a great deal of their own teaching
      and learning. The curriculum is centered around patient cases and is called
      patient-centered learning (PCL). The curriculum includes traditional lectures and
      laboratories supporting faculty-generated learning objectives. Endocrine
      physiology is taught in year one, utilizing four weeks of patient cases that
      emphasize normal structure and function of endocrine systems. Endocrine
      physiology is revisited in year two, which is primarily focused on pathobiology.
      The PCL curriculum, with emphasis on the endocrine component, is described in
      detail along with key portions of an endocrine case.

PMID- 11824206
TI  - Endocrine PBL in the year 2000.
AB  - The Southern Illinois University School of Medicine (SIU-SOM) has utilized
      problem-based learning (PBL) in its curriculum since 1981, when Dr. Howard
      Barrows joined the faculty. From 1989 to 2000, SIU-SOM implemented two parallel
      curricula for the basic science years (years I and II), one curriculum being a
      problem-based learning curriculum (PBLC). An executive decision to design and
      implement a single curriculum, to begin in Fall 2000, fostered a review of
      existing pedagogy upon which to base this new curriculum: C2000. The results of
      this review, which considered formal outcome measures as well as internal review
      in consideration of the institutional mission, led to PBL becoming the
      predominant pedagogy for C2000, albeit with some modifications from its PBLC
      predecessor. C2000, then, represents the third iteration of PBL in use at SIU
      SOM, and its design and rationale offer insight for the teaching of Endocrine
      Physiology in a PBLC.

PMID- 11824207
TI  - Small group teaching: clinical correlation with a human patient simulator.
AB  - The popularity of the problem-based learning paradigm has stimulated new interest
      in small group, interactive teaching techniques. Medical educators of physiology
      have long recognized the value of such methods, using animal-based laboratories
      to demonstrate difficult physiological principles. Due to ethical and other
      concerns, a replacement of this teaching tool has been sought. Here, the author
      describes the use of a full-scale human patient simulator for such a workshop.
      The simulator is a life-size mannequin with physical findings (palpable pulses,
      breath/heart sounds, blinking eyes, etc.) and sophisticated mechanical and
      software models of the cardiovascular and pulmonary systems. It can be connected
      to standard physiological monitors to reproduce a realistic clinical environment.
      In groups of 10, first-year medical students explore Starling's law of the heart,
      the physiology of the Valsalva maneuver, and the function of the baroreceptor in
      a clinically realistic context using the simulator. With the use of a novel pre
      /postworkshop assessment instrument that included student confidence in their
      answers, student confidence improved for all questions and survey items following
      the simulator session (P < 0.0001). The students give these laboratory exercises
      uniformly superior evaluations with > 85% of the students rating the workshop
      "very good" or "excellent".

PMID- 11824208
TI  - Hemodynamics for medical students.
AB  - The flow of blood through the cardiovascular system depends on basic principles
      of liquid flow in tubes elucidated by Bernoulli and Poiseuille. The elementary
      equations are described involving pressures related to velocity,
      acceleration/deceleration, gravity, and viscous resistance to flow (Bernoulli
      Poiseuille equation). The roles of vascular diameter and number of branches are
      emphasized. In the closed vascular system, the importance of gravity is
      deemphasized, and the occurrence of turbulence in large vessels is pointed out.

PMID- 11824209
TI  - Toward consistent definitions for preload and afterload.
AB  - Significant differences exist among textbook definitions for the terms preload
      and afterload, leading to confusion and frustration among students and faculty
      alike. Many faculty also chose to use in their teaching simple terms such as "end
      diastolic volume" or "aortic pressure" as common-usage approximations of preload
      and afterload, respectively, but these are only partial representations of these
      important concepts. Straightforward definitions both of preload and afterload
      that are concise yet still comprehensive can be developed using the Law of
      LaPlace to describe the relationships among chamber pressure, chamber radius, and
      wall thickness. Within this context, the term "preload" can be defined as all of
      the factors that contribute to passive ventricular wall stress (or tension) at
      the end of diastole, and the term "afterload" can be defined as all of the
      factors that contribute to total myocardial wall stress (or tension) during
      systolic ejection. The inclusion of "wall stress" in both definitions helps the
      student appreciate both the complexities of cardiac pathophysiology and the
      rationale for therapeutic intervention.

PMID- 11824210
TI  - Design and evaluation of a national set of learning objectives: the medical
      physiology learning objectives project.
AB  - In 1998, the American Physiological Society (APS) and the Association of Chairs
      of Departments of Physiology (ACDP) began collaboration on a project to develop a
      set of physiology learning objectives for medical students. Over the next 2
      years, more than 50 physiologists collaborated in the development a comprehensive
      draft containing its 695 learning objectives. Faculty in 31 medical schools in
      the United States, Canada, and Puerto Rico evaluated these objectives. On the
      basis of this evaluation, the ACDP recommended deleting 13 of them. The final
      project, containing 682 objectives, was approved in December 2000 by the ACDP and
      published on the APS website http://www.the
      aps.org/education/MedPhysObj/medcor.htm. The identification of the "content" of
      medical physiology instruction provides the APS and the ACDP with a tool to
      introduce emerging topics, such as the physiology of aging and gender
      differences, at a national level. The medical physiology learning objectives
      project provides a guide for directing current and future medical physiology
      instruction in the United States.

PMID- 11824211
TI  - Cardiovascular pressure-flow relationships: what should be taught?
AB  - Cardiovascular physiology reflects the interrelations of flow, pressure, and
      resistance. Undergraduate students are often confused by the complexity of the
      system. This symposium presents a sequential presentation of the underlying
      concepts, building on analogies, past experience, and conceptual models to allow
      students to develop a physiologically appropriate understanding of cardiovascular
      physiology.

PMID- 11824212
TI  - Pulmonary and renal pressure-flow relationships: what should be taught?
AB  - This article is from a symposium presented at the annual meeting of the Human
      Anatomy and Physiology Society (HAPS) on June 11, 2000. The presentation was
      funded under the auspices of a National Science Foundation Course, Curriculum,
      and Laboratory Improvement Program entitled "Development of Active Learning
      Materials for Physiology and Functional Anatomy: A Cooperative HAPS-APS
      Initiative." This symposium was part of the first module to be developed on
      "gradients and conductances: what flows where and why?" This presentation was
      designed to model the usefulness of the general model of gradients and
      conductances in the physiology and pathophysiology of the respiratory and renal
      systems. Thirteen different examples of pressure-flow-resistance and
      concentration-flux relationships are introduced; several ideas for active
      learning activities and simple figures appropriate for undergraduate physiology
      classes are included. The symposium assumes that undergraduate students have
      already learned about diffusion, osmosis, and the basic principles of
      cardiovascular physiology. The presentation was designed to follow a symposium
      entitled: "Cardiovascular pressure-flow relationships: what should be taught?"

PMID- 11824213
TI  - Ancient templates: the classical origins of psychoanalysis.

PMID- 11824214
TI  - Therapeutic action: a new theory.
AB  - This article introduces a new clinical construct: "Interaction structure."
      Interaction structures are recurrent, mutually influencing patterns of
      interaction between therapist and patient. The experience, recognition, and
      comprehension of the meaning of such repetitive interactions are a fundamental
      component of therapeutic action. This bipersonal or dyadic model attempts to
      bridge those theories of therapeutic action that focus on insight and self
      understanding and those that emphasize the patient's experience of the therapist.
      In this model, insight and relationship have complementary roles, since
      psychological knowledge of the self can develop only in the context of a
      relationship where the therapist endeavors to understand the mind of the patient
      through the medium of their interaction. The interaction-structure construct and
      its associated theory of therapeutic action are based on empirical research. A
      single-case research model is described that shows that process and outcome in
      psychoanalytic treatments can be studied within individual treatments in a way
      that is scientifically persuasive. Three case studies illustrate how each patient
      therapist pair has a unique interaction pattern, and how these patterns are
      linked to therapy outcome. The essential place of formal, empirical study in
      psychoanalytic theorizing and in clinical work is demonstrated.

PMID- 11824215
TI  - Psychotherapy for massively traumatized refugees: the therapist variable.
AB  - In the treatment of severe posttraumatic stress disorder (PTSD), much emphasis is
      put on techniques, especially behavioral therapies. Such techniques negate the
      importance of the therapist as an individual in the treatment of complex PTSD as
      presented in severely traumatized refugees. The specific difficulties encountered
      by this population and the therapist responses are discussed: the need to tell
      the trauma story and the therapist's ability to listen; the patient's need for
      constancy and therapist's ability to stay; the patient's need to give and the
      therapist's ability to receive; the patient's problem with evil and the
      therapist's ability to believe. Case examples illustrate the approach and then
      discuss how generalizable this experience is to other populations. Research
      implications are suggested.

PMID- 11824216
TI  - Is couple therapy indicated for borderline personality disorder?
AB  - The healing aspects of intimate relationships are being recognized by therapists
      and supported by empirical findings. Little has been written regarding the
      indications for couple therapy for individuals with borderline personality
      disorder. This paper proposes a three-level hierarchy for deciding on the
      suitability of couple therapy for patients with borderline personality disorder.
      The hierarchy is based on three separate borderline behavioral clusters-
      impulsive, identity, and affective--that should be utilized to direct the
      application of couple therapy to specific patients. The three levels are
      illustrated by case examples. Delineation of the indications for couple therapy
      for borderline patients will foster further theoretical and empirical work in the
      area.

PMID- 11824217
TI  - Active treatment of depression.
AB  - Despite advances in medication and psychotherapeutic methods, most patients with
      depression are subject to frequent recurrences and lead damaged lives even when
      they do not meet criteria for an episode. This article suggests an active,
      directive, educational treatment approach for patients with depression, centered
      on two tools: 1. a Mood Journal, focusing on reestablishing the connection
      between the patients' mood changes and their external life; and 2. a series of
      "aphorisms" of depression, meant to be shared with patients early in treatment.
      These are assertions about the nature of depression and recovery from it, which
      help patients move toward taking an active role in questioning how the condition
      affects them.

PMID- 11824218
TI  - Enhancing self-belief with EMDR: developing a sense of mastery in the early phase
      of treatment.
AB  - Deep inside each of us is a seed that holds our vision of truth, peace, and
      happiness. Our early childhood attachments, societal influences, and innate
      capacity determine how well that seed is nurtured and the deepest inner vision is
      set free. This article is about the ways that vision becomes clouded by
      attachment deficits, trauma, and subsequent symptoms. The deep inner wish to heal
      allows for transformation, and approaches like Eye Movement Desensitization and
      Reprocessing, and hypnotherapy can assist in creating a more rapid acceleration
      of trauma resolution and transformation of self.

PMID- 11824219
TI  - Freud's unfortunates: reflections on haunted beings who know the disaster of
      severe trauma.
AB  - The forms of dissociation are multiplex and must include a type of dissociation
      that represents human beings' fundamental inability to process and represent
      severe trauma. This article posits a form of dissociation--resulting from trauma-
      linked to disastrous knowledge, signifying a person's incapacity to use language
      and symbol to organize the core of the traumatic experience in terms of
      semantically structured self-in-relation. Catastrophic knowledge of severe trauma
      is unexperienced experience that paradoxically stands for an indescribable core
      of an event that undermines self-in-relation and the concomitant capacities for
      language, narrative, and knowledge. This irretrievable unexperienced experience
      continues to haunt despite a person's recovery. This perspective points to the
      limits of therapy and the necessity to establish and maintain a relationship of
      trust and loyalty in the face of an event that annihilates self-in-relation.
      Included in this work are the therapeutic tasks of serving as a witness and a
      container of the unnamable horror.

PMID- 11824220
TI  - A religious psychiatrist's ethnographic self-report.
AB  - The religious identity of psychiatric patients is deemed important as it may
      impact upon the understanding of patients' problems and the quality of the
      therapeutic relationship. It would seem important that the psychiatrist should
      also be sensitive to the role of his/her own religious identity and its effect on
      clinical work. Nevertheless, even in studies by and about psychiatrists who have
      religious roles within a community, this component has tended to be ignored. A
      series of self-observations are offered by a religious Jewish psychiatrist to
      describe the effect of religious identity on himself and his patients during
      clinical work in Israel. Three types of situations were apparent: when he was
      unsure about his religious identity, when he was unsure about his professional
      identity, and when he was dealing with essentially religious rather than
      psychiatric issues and having to differentiate between his own role and that of a
      rabbi. These observations support the need to be sensitive to the effect of one's
      religious identity on clinical work, while appreciating that, as Andrew Sims has
      stated, the psychiatrist's "attitude towards the patient who shares his faith is
      as a fellow believer and not as a priest".

PMID- 11824221
TI  - Commentary to praxis paper.

PMID- 11824222
TI  - Matter, spacetime and the vacuum.
AB  - We distinguish three historical and scientific views of matter, spacetime, and
      the relationship between them: the absolute approach of Newton, the relational
      approach most often associated with Mach, and a third, geometrical approach which
      inspired Einstein and continues to drive efforts toward a unified theory of
      fundamental interactions today. Which is correct? We suggest that this is, to a
      large extent, an "ill-posed question," reminiscent of the wave/particle debate in
      earlier times. The boundary between matter and spacetime is no longer easy to
      draw, and it is likely that they are complementary aspects of the same reality.
      There is no clearer illustration of this than the modern view of the vacuum. We
      review the importance of this concept in cosmology, and explore the extent to
      which the old idea of an "empty" vacuum might still be maintained. If the real
      cosmological vacuum is far from empty, as observations now suggest, then it may
      be possible to achieve an even simpler goal: a Universe with a net energy of
      zero.

PMID- 11824223
TI  - DNA vaccines.
AB  - Immunization by genes encoding immunogens, rather than with the immunogen itself,
      has opened up new possibilities for vaccine research and development and offers
      chances for new applications and indications for future vaccines. The underlying
      mechanisms of antigen processing, immune presentation and regulation of immune
      responses raise high expectations for new and more effective prophylactic or
      therapeutic vaccines, particularly for vaccines against chronic or persistent
      infectious diseases and tumors. Our current knowledge and experience of DNA
      vaccination is summarized and critically reviewed with particular attention to
      basic immunological mechanisms, the construction of plasmids, screening for
      protective immunogens to be encoded by these plasmids, modes of application,
      pharmacokinetics, safety and immunotoxicological aspects. DNA vaccines have the
      potential to accelerate the research phase of new vaccines and to improve the
      chances of success, since finding new immunogens with the desired properties is
      at least technically less demanding than for conventional vaccines. However, on
      the way to innovative vaccine products, several hurdles have to be overcome. The
      efficacy of DNA vaccines in humans appears to be much less than indicated by
      early studies in mice. Open questions remain concerning the persistence and
      distribution of inoculated plasmid DNA in vivo, its potential to express antigens
      inappropriately, or the potentially deleterious ability to insert genes into the
      host cell's genome. Furthermore, the possibility of inducing immunotolerance or
      autoimmune diseases also needs to be investigated more thoroughly, in order to
      arrive at a well-founded consensus, which justifies the widespread application of
      DNA vaccines in a healthy population.

PMID- 11824224
TI  - Optical spectroscopy of individual objects.
AB  - With the introduction of single-molecule spectroscopy it was immediately realised
      that studying molecules and molecular aggregates individually opens up a
      completely new approach to elucidate information commonly washed out by the
      ensemble average process. In contrast with ensemble experiments, this technique
      permits us to determine the whole distribution of parameters rather than their
      moments. This allows a more direct verification of theoretical models without the
      need to average over (unknown) distributions to calculate observables. Here we
      illustrate how single-molecule spectroscopy can be utilised to circumvent the
      classical diffraction limit of microscopy and show an investigation of the
      electronic structure of pigment protein complexes that are relevant for bacterial
      photosynthesis.

PMID- 11824225
TI  - Elbe river flood peaks and postwar agricultural land use in East Germany.
AB  - Collectivization of farmland since the 1950s has changed the agricultural land
      use in former East Germany. Single fields on the collective farms became
      increasingly large and were cultivated with increasingly heavy farm equipment.
      This led to large-scale physical degradation of arable soils, enhancing the
      formation of surface runoff in periods with prolonged and excessive
      precipitation. The extent to which this development may have affected the
      discharge behavior of the main East German river, the Elbe, has so far not been
      studied. We analyzed the flood peaks of the Elbe during the past century (1900
      2000). The flood discharge behavior of the Elbe has apparently changed
      significantly since the 1950s. Although climate changes may be involved, we
      conclude that the Elbe flood peaks, recorded since 1950, are related to the
      changes in postwar agricultural land use in former East Germany. To restore the
      degraded farmland soils, a change in agricultural land use may be necessary.

PMID- 11824226
TI  - Reproductive division of labour coevolves with gall size in Australian thrips
      with soldiers.
AB  - An analysis of multiple species of Australian gall-inducing thrips with soldiers
      reveals a significant negative correlation between the size of gall produced and
      the reproductive division of labour. This correlation suggests that the evolution
      of smaller galls limited the available space and feeding sites for the offspring
      of female soldiers, and was a major factor that led to the evolution of an
      altruistic caste in the gall-inducers. We argue that high levels of inbreeding by
      singly mated foundresses and incestuous mating by her soldier offspring are key
      to this evolutionary relationship because they make the relatedness of a female
      soldier to her daughters and sisters approximately equal. Evidence that
      relatedness plays an important role is strengthened by the observation of outbred
      multiply mated foundresses and unbiased sex ratio of dispersers in Oncothrips
      waterhousei, and the inference that both gall volume and skew decreased along
      this lineage.

PMID- 11824227
TI  - Evolution of locomotory attachment pads of hexapods.
AB  - This study shows that, in their evolution, hexapods have convergently developed
      two distinctly different mechanisms to attach themselves to a variety of
      substrates during locomotion. The first mechanism is provided by hairy surfaces
      and the second one by smooth flexible pads. The main similarity of both
      mechanisms is that the structured pad surface or particular properties of pad
      materials guarantee a maximum real contact with diverse substrata, regardless of
      their microsculpture. Ten characters of the two alternative designs were coded
      and analyzed together with a data matrix containing 105 additional morphological
      characters of different stages and body parts. The analysis demonstrates that
      similar structures (arolium, euplantulae, hairy tarsomeres) have evolved
      independently in several hexapod lineages. The evolution of flight and the
      associated necessity of being able to cling to vegetation or other substrates are
      suggested to be major triggers for the evolution of attachment structures.

PMID- 11824228
TI  - [Technique of rectum resection and excision with special reference to TME].
AB  - Rectal cancer poses an immense challenge within the field of laparoscopic
      surgery. Sufficient enlargement on a monitor and improved instruments enable an
      optimal preparation and the total mesorectal excision. The standardized technique
      is the key to success. By December 2000, 138 rectal carcinomas were operated upon
      in laparoscopic technique at our hospital. The operating steps are adapted to the
      criteria of the "open" surgery. A rectal extirpation was performed in 13%, a
      continuity resection in 87%. The rate of local recurrence was 3.8% after a follow
      up of 40 months, the survival rate in curatively operated patients was 90%.

PMID- 11824229
TI  - [Tumor surgery and quality of life--reconstructive rectal surgery].
AB  - Numerous innovations in recent years have allowed a variable therapeutic approach
      for rectal cancer with a concomitant drastic reduction in extirpations. This
      development was paralleled by an increasing research into postoperative quality
      of life in colorectal cancer. This showed that a very ambitious preservation of
      the sphincter does not automatically lead to good quality of life. On the other
      hand is the expectation of healing a generally important factor in a good quality
      of life. Whether routine evaluation of quality of life data does in fact improve
      medical care is an open question.

PMID- 11824230
TI  - [Laparoscopic restorative proctocolectomy in ulcerative colitis and colonic
      polyps].
AB  - With increasing experience, laparoscopic techniques have been applied even to
      extended colorectal operations as restorative proctocolectomy in ulcerative
      colitis and familial adenomatous polyposis. After initial medial transection of
      the three main vascular pedicles, the colon is dissected free laterally, from the
      sigmoid orally towards the ileum. The rectum is mobilized down to the pelvic
      floor. Over a Pfannenstiel incision, the bowel is extracted and the pouch is
      created. The anastomosis is completed in double-stapling technique. At two
      departments, 27 patients have been operated on. The median time of operation was
      320 min (180-540). The median length of hospital stay was 8.1 days. There was no
      postoperative mortality. The complication rate was similar to conventional
      surgery at the same institutions. Three patients had to be re-operated on, two
      for ileal obstruction close to the pouch, one patient for bleeding from the
      pouch. In restorative proctocolectomy, laparoscopic techniques prove to be safely
      feasible. They have the potential to become an appealing alternative to open
      surgery.

PMID- 11824232
TI  - [How safe is intracorporeal anastomosis?].
AB  - A recent German multi-centre study comprising 3070 laparoscopic colorectal
      resections indicates that complete intracorporeal anastomoses are done in only
      1.8%. In agreement with the literature, technically demanding hand-sutured
      anastomoses are no common practice either. Intracorporeal anastomosis is usually
      done using endoscopic linear stapling devices or the conventional circular
      stapler by performing end-to-end, end-to-side, and side-to-side anastomoses.
      These techniques are more frequently used in the upper than in the lower
      gastrointestinal tract. The date published so far, however, indicate that the
      complete intracorporeal anastomosis is a save technique in the hands of
      laparoscopically experienced surgical teams. This technique has very low rates of
      postoperative stenoses (0-10%) and, furthermore, very low rates of postoperative
      anastomotic leakages (0-8%).

PMID- 11824231
TI  - [Anorectal ulcers--etiology, diagnosis, therapy (simple rectal ulcer, radiogenic
      ulcer, CED].
AB  - Ulcers of the anorectal region are very variable in etiology and morphology.
      Often differential diagnosis is even possible by (excisional-)biopsy. As they are
      symptoms of any kind of disease, therapy has to be derived from this disease.
      Therefore surgery often only plays an additional part besides clearing the
      diagnosis, although the surgeon is mostly the first consultant, so being
      responsible for ongoing therapy. Some special diseases, their problems and
      therapeutical options, are described in detail.

PMID- 11824233
TI  - [History of lymphadenectomy].
AB  - The present reflection of lymphadenectomy's history shows that the following
      questions have been discussed since about 100 years: How does the lymph node
      dissection affect the treatment of cancer? Does it reduce the local recurrence
      rate? Does a lymph node dissection improve the survival rate or permit a more
      specific staging of the tumour's extension? The principles of metastatic ways as
      well as their mechanisms have already been discussed in the 1920s.

PMID- 11824234
TI  - [Precancerous conditions and neoplasms of the anal area].
AB  - Classification of this lesions could be done concerning localisation and
      histological type. Squamous cell carcinoma of the anal canal are the most often
      to be found, but overall neoplasias in this region are very seldom. The most
      important role in pathogenesis seems to play infection with HPV viruses. Symptoms
      are in the beginning unspecific and similar to other common proctological
      diseases. Proctological diagnostic procedures are to be combined with cytological
      methods. Therapeutic management depends on malignant potential of the lesions and
      contains local excision, total operation and combined radiochemotherapy, which is
      today considered standard therapy of squamous cell carcinoma of the anal canal.

PMID- 11824235
TI  - [Endoluminal therapy of neoplastic changes in the gastrointestinal tract: Barrett
      esophagus--from the viewpoint of the surgeon].
AB  - The need for radical subtotal esophagectomy and extensive lymphadenectomy in
      patients with early Barrett cancer, i.e. T1 tumors, is increasingly questioned.
      Based on the principles of surgical oncology, the precancerous nature of Barrett
      esophagus, and the high rate of lymph node metastases in patients with T1b
      tumors, the minimal extent of the procedure for early Barrett cancer must include
      the entire segment of the distal esophagus covered by intestinal metaplasia and a
      regional lymphadenectomy. In adequately selected patients this can be achieved by
      a limited surgical procedure with transhiatal resection of the distal esophagus
      and jejunum interposition, but not by endoscopic mucosal ablation or endoscopic
      mucosa resection. The high recurrence rates after endoscopic interventions does
      not support the use of these techniques in operable patients.

PMID- 11824236
TI  - [Endoluminal therapy of neoplastic changes of the gastrointestinal tract:
      questionable and reliable aspects. Early stomach carcinoma: surgical treatment].
AB  - Early gastric cancer (EGC) is defined as gastric carcinoma limited to the mucosa
      and submucosa of the gastric wall, corresponding to UICC stage pT1a or pT1b. The
      overall prognosis is excellent, with 5-year survival rates up to 95% reported by
      Japanese institutions as well as in some series from Europe and the USA. However,
      the therapeutic concept still is indifferent. New staging methods and advances in
      the endoscopic and laparoscopic treatment opened new fields of therapeutic
      approaches. Therefore, referring to the results of japanese studies, for defined
      subtypes of EGC an endoscopic approach can be recommended. This, however, is
      related to a close follow up of these patients. In case of a surgical resection,
      radical D2-lymphadenectomy should be performed, especially in patients with
      submucosal invasion.

PMID- 11824237
TI  - [Bleeding in the lower intestinal tract: indications and results of endoscopic
      therapy].
AB  - Colonoscopy is the method of choice in clarifying an intestinal bleeding if upper
      gastrointestinal bleeding is excluded. It allows identification of the bleeding
      source and immediate therapy by thermal, mechanical and injection procedures.
      Depending on the origin of the bleeding, the applied method and the examiner's
      abilities, hemostasis can be achieved in up to 100% of the cases with low
      rebleeding and complication rates. Because there are only few prospective
      randomized trials comparing different endoscopical hemostasis methods, the
      examiner's competence and the local availabilities of endoscopic procedures are
      decisive for the results of endoscopic therapy.

PMID- 11824238
TI  - [Local resection in treatment of rectal tumors].
AB  - We treated 160 patients (96 males, 64 females) with a mean age of 66 +/- 12
      years. 63 patients presented adenomas (AD) and 97 adenocarcinomas (ADC). In the
      ADC group 32 patients received preoperative chemoradiation (RT + CT), and 15
      postoperative RT. In 7 patients with RT + CT the tumor disappeared. No hospital
      mortality was recorded. Morbidity was observed in 13% of AD group and 18% of ADC
      group. Hospital stay was less than 7 days for 72% of patients. Stages were: 10
      pTis, 40 pT1, 29 pT2, 18 pT3. Recurrence was observed in 7 (11%) of AD and 23/97
      ADC (24%). 0 pTis, 12% pT1, 24% pT2, 61% pT3. No patient with RT + CT and
      negative margins had recurrence with a minimum follow-up of 2 years (11
      patients). Five-year cumulative survival was 100% for pTis, 92% for pT1, 75% for
      pT2 and 69% for pT3.

PMID- 11824239
TI  - [Response evaluation--pathway for accurate indications development].
AB  - Only patients, which respond to neoadjuvant therapy and in which a subsequent
      complete resection (R0) is possible, demonstrate a significant survival advantage
      compared to non-responders. Therefore, a sensitive response evaluation is of high
      clinical interest. Response evaluation by endoscopy, biopsy, endoluminal
      ultrasound or by CT scan showed unfavourable and overall nor reliable results. In
      recent studies, a accurate response prediction employing 18FDG-PET seems to be
      possible. Following neoadjuvant chemoradiation of esophageal cancer, a sensitive
      differentiation between responders and non-responders was possible in a
      retrospective study. In the beginning are investigations, to differentiate
      already after two weeks of therapy between both groups of patients.

PMID- 11824240
TI  - [Recent aspects in endoscopic and surgical antireflux therapy].
AB  - In addition to well established operative procedures for the treatment of
      gastroesophageal reflux disease, several laparoscopic, combined laparo
      endoscopic, endoscopically guided or assisted, and purely endoscopic procedures
      have been developed in recent years (semiabsorbable antireflux scarf, laparo
      endoscopic intraluminal valvuloplastic, endoluminal gastroplication procedure (C.
      R. Bard Inc.), endoscopic radiofrequency delivery to the lower esophageal
      sphincter (= Stretta procedure, Curon Medical Inc.), endoscopic implantable
      biopolymer (Enteryx) (= LESA procedure, Enteric Medical Technologies Inc.). At
      present, initial positive experimental and clinical results demonstrate a
      possible reinforcement of the reflux barrier at the esophagogastric junction.
      Information on a broader clinical application, a possible spectrum of
      indications, and long-term results on the safety and endurance of these
      procedures are not yet available.

PMID- 11824241
TI  - [Long-term drug therapy versus antireflux surgery in chronic reflux].
AB  - In endoscopy-negative reflux disease just 25% remain in remission after drug
      therapy, in reflux oesophagitis only 10%. Long-term management is therefore
      mandatory in this quality of life-impairing chronic disorder. Following the
      GENVAL consensus conference proton pump inhibitors (PPI) should be used primarily
      in a step-down regimen; isomeric PPIs reduce duration of acute therapy by 50%.
      According to Klinkenberg-Knol et al. 100% of all patients with H2-resistant
      reflux oesophagitis are asymptomatic and free of recurrency when dosage of PPI is
      adapted to a higher level. The same result was obtained in the prospective study
      by Lundell et al. comparing fundoplication and long-term management with
      omeprazole for 3 years.

PMID- 11824242
TI  - [Organizational prerequisites for multimodality therapy concepts].
AB  - The increasing use of multimodal therapies confronts clinics with the need to
      create new organisational structures. The high degree of specialisation
      necessitates that the separate disciplines seek ways of working closer together.
      This is particularly the case when staging results have to be evaluated and a
      multimodal therapy course chosen or when quality management issues and the
      coordination of different steps of a treatment are being considered. By
      establishing disease-oriented organisational structures and by institutionalizing
      interdisciplinary cooperation, e.g. in daily tumor board meetings and in fixed
      disease management teams, the organisational prerequisites for implementing
      multimodal therapies are created.

PMID- 11824243
TI  - [Role of the surgeon in pain management in oncological surgery].
AB  - Cancer pain patients need a causal therapy whenever possible. Often surgical
      treatment offers effective pain therapy (e.g. biliodigestive anastomosis in
      obstructive cancer). In addition, chemotherapy and/or radiation may be indicated.
      Simultaneous symptomatic pain management according to the guidelines for pain
      therapy in cancer pain should be started. In general, therapy of chronic
      malignant pain should follow the WHO schema for cancer pain. Surgery and medical
      pain therapy can reduce 96-98% cancer pain effectively.

PMID- 11824244
TI  - [The status of port-site recurrence].
AB  - Since laparoscopic surgery has been applied to cancer, an increased number of
      secondary tumors implanted in the abdominal wall have been reported. Quality of
      surgery is paramount in the incidence of port-site recurrences. In large
      prospective series of laparoscopic colorectal surgery, their incidence (around
      0.85%) was similar to that reported in open surgery (0.6 to 1.6%) while it is
      higher for unapparent gallbladder cancer (around 15%) due to direct wound
      contamination. Viable tumor cells are seeded by inadequate surgical technique or
      released by advanced tumors. Tumor cells are carried across the abdominal cavity
      by peritoneal fluid currents and surgical instruments, not by CO2
      pneumoperitoneum. CO2 modifies the morphology of mesothelial cells and inhibits
      peritoneal macrophages. Differences in retroperitoneal/subserosal/intraluminal
      tumor xenograft models show that CO2 laparoscopy reduces tumor growth when
      compared to gasless laparoscopy and laparotomy. The local effects of
      pneumoperitoneum in the wound might be counteracted by using inert gases such as
      helium, drug-loaded CO2 or various antiadhesive or cytotoxic agents. In clinical
      practice, port-site recurrences can be effectively prevented by careful surgical
      technique and prophylactic wound irrigation.

PMID- 11824245
TI  - [Primary tumors of the liver: radiologic interventional procedures].
AB  - Primary liver tumors are one of the most common malignant tumors worldwide.
      Surgical resection of the tumors is considered the only potentially curative
      therapy. It has been estimated that only 20%-30% of patients with HCC
      (hepatocellular carcinoma) are surgical candidates. For this reason a number of
      alternative therapies have been used for the treatment of HCC. These include
      transarterial chemoembolisation (TACE), percutaneous alcohol instillation (PAI)
      and thermal ablative techniques. Thermal ablation for the treatment of HCC
      include both freezing (cryoablation) and heating (radiofrequency, microwave,
      laser and high-intensity focussed sonography) techniques. Of these techniques,
      percutaneous radiofrequency ablation (PRFA) is increasingly used for the local
      tumor destruction. The low rate of complications and the technical development
      increasing the efficacy of PRFA have shown that this is a very promising and safe
      technique.

PMID- 11824246
TI  - [Regional chemotherapy--perfusion of the extremities].
AB  - Hyperthermic isolated limb perfusion with cytostatic drugs (HILP) is indicated in
      locoregional recurrences of malignant melanoma of the limbs. As a neoadjuvant
      treatment it is also used for non-curatively resectable soft tissue sarcoma or
      their recurrences on the extremities. Up to now, melphalan is still the standard
      drug in HILP for malignant melanoma. With melphalan, complete response can be
      achieved in 65-80% for clinically detectable in transit metastases (+/- regional
      lymph node metastases). The combination of tumor necrosis factor (TNF) alpha with
      melphalan has considerably improved response rates of HILP in sarcoma. In more
      than 80% of the patients the otherwise necessary amputation of the limb can be
      avoided. The combination of TNF with other drugs than melphalan could possibly
      further improve results of HILP in sarcoma patients. The high rate of local
      recurrences of malignant melanoma after HILP poses an unsolved problem yet.

PMID- 11824247
TI  - [Classification of peritoneal carcinosis and differentiation from pseudomyxoma
      peritonei].
AB  - Pathological classification of peritoneal carcinomatosis depends on the
      underlying tumor-entities. For confirmation cytodiagnostic is a simple and
      reliable method allowing differential diagnosis of non-epithelial primaries. For
      the early detection of peritoneal dissemination peritoneal lavage should be done
      routinely at first operation of gastrointestinal tumors. Pseudomyxoma peritonei
      signifies a clinical condition, pathological classification requires evaluation
      of the primary lesion most often localised in the appendix which should be
      resected in all instances and entirely submitted for histological examination.
      For prognostic consideration additionally the peritoneal implants must be
      thoroughly sampled.

PMID- 11824248
TI  - [Principle and indications for debulking operation in peritoneal carcinosis].
AB  - Recent studies demonstrate that cytoreductive surgery (debulking) is a feasible
      option for the treatment of peritoneal carcinomatosis. Indications for such an
      approach, often combined with intraperitoneal chemotherapy, are malignant
      conditions of the appendix, the colon, the ovary and peritoneal mesothelioma.
      Cytoreduction may also be performed in gastric carcinoma predominantly however in
      prospectively planned studies. Carcinomas of the hepato-pancreatobiliary system
      should not be subjected to cytoreduction. The operation itself consists of
      complete peritonectomy of the parietal peritoneum, multivisceral resection
      including cholecystectomy, gastric and colonic resection as well as anterior
      rectal resection. Morbidity and mortality of these procedures are 30% and 1-6%
      respectively. Depending on the histology of the primary tumor, 5 years survival
      rates of up to 50-75% can be achieved.

PMID- 11824249
TI  - [Preventive therapy of HNPCC--a study concept].
AB  - Due to different pattern of penetrance and heterogeneity, the role of
      prophylactic surgery must be individually defined for every hereditary cancer
      predisposition. For HNPCC (hereditary nonpolyposis colorectal cancer) subtotal
      colectomy at the time of colorectal cancer diagnosis is being recommended by the
      Cancer Genetics Studies Consortium Recent Guidelines from the DGVS (Deutsche
      Gesellschaft fur Verdauungs- und Stoffwechselkrankheiten) state that to date no
      general recommendation favouring this approach can be made. The open question is:
      how effective is segmental resection and endoscopic surveillance in given time
      intervals compared with the reduction of risk by performing extended
      (prophylactic) surgery. Also the issue of dealing with rectal cancer as the first
      primary in HNPCC patients must be addressed. In order to answer these questions
      and after the lessons learned from BRCA mutation carriers and prophylactic
      mastectomies, quality of life measurement is mandatory for this study.

PMID- 11824250
TI  - [Benign tumors--surgical indication?].
AB  - Diagnostic and therapeutic options of the benign tumors in the anal region will
      be discussed. There is no systematic scheme for these tumors depending on the
      polymorph aspects and different matrices in the borderline between ecto- and
      entoderma. Because of the localisation either in perianal skin, fossa
      ischiorectalis or in the retrorectal space there is a need of different
      therapeutic options and approaches.

PMID- 11824251
TI  - [Clinical and biochemical diagnosis of pHPT and sHPT, surgical indications from
      the internal medicine viewpoint].
AB  - Hypercalcemia and a relative nonsuppressibility of parathyroid hormone by calcium
      are the biochemical hallmarks of primary hyperparathyroidism. An elevated PTH
      level should be defined in a highly sensitive and specific test system. Primary
      HPT is the single major cause of hypercalcemia in outpatients. A definitive
      medical option to manage PHP does not exist. Surgical neck exploration by an
      experienced surgeon has a very high success rate for cure in both symptomatic and
      asymptomatic disease forms. Secondary HPT is mostly due to renal failure.
      Nonsuppressibility of PTH by use of vitamin D sterols indicates parathyroid gland
      hyperplasia and autonomy of PTH secretion. Surgery should correct PTH excess and
      should lead to an optimal bone status.

PMID- 11824252
TI  - [Monitoring the recurrent laryngeal nerve as a routine measure in thyroid gland
      surgery].
AB  - Intra-operative monitoring of the recurrent laryngeal nerve by electromyography
      of the inner laryngeal muscles facilitates the nerves preparation. The positive
      and negative predictive values of the method with regard to vocal cord function
      have not sufficiently been examined. Prospective randomized data concerning the
      usefulness with regard to permanent nerve palsy rates are lacking. The impressive
      reduction in palsy rates over the last 20 years is due to routine preparation and
      protection of the visualized nerve. This principle must not be abandoned.
      Depending on the setting, neuromonitoring may be a valuable help. It is not an
      obligation in thyroid surgery.

PMID- 11824253
TI  - [Neurostimulation of the recurrent laryngeal nerve--a routine method in thyroid
      gland surgery?].
AB  - INTRODUCTION: Thyroid operations belong to the most frequent procedures in
      Germany (100,000/year). An important quality parameter is the incidence of
      postoperative recurrent nerve paralysis. Intraoperative identification by
      visualization of the nerve with a paralysis rate of 1% is the present gold
      standard in dedicated centers. PROBLEM: Can this results be further improved by
      use of an intraoperative neuromonitoring system (NM). RESULTS: The use of NM is
      helpful in difficult situations (recurrent goiter, advanced carcinoma, anatomic
      variants), but a quality improvement is not yet proven. CONCLUSION: NM can not
      replace the current nerve identification by meticulous preparation of anatomic
      structures. It should be used at the discretion of the operative surgeon.

PMID- 11824254
TI  - [Therapy of acute liver failure].

PMID- 11824255
TI  - [Medical-surgical evaluation of living liver donors].
AB  - The living related liver segment transplantation is an established procedure in
      liver transplantation for children and adults. The evaluation of a possible donor
      should consider the following subjects: (1) Assessment of organ quality by
      imaging of size and anatomy of the liver and exclusion of the unknown liver
      diseases by labority analysis and liver biopsy. (2) Risk assessment of the
      potential organ donor by exclusion of preexisting diseases increasing the risk of
      surgery, including thromboembolic risk factors. (3) Psychological evaluation.
      Nevertheless the evaluation procedure should by practicable, convenient for the
      organ donor and cost effective. This can be realized by a stepwise program.

PMID- 11824256
TI  - [Management of biliary complications after orthotopic liver transplantation].
AB  - In this retrospective analysis we report our results after liver transplantation
      regarding biliary complications (bc) and the effectiveness of endoscopic therapy.
      In the last 4 1/2 years we found 13 biliary leaks (7 in combination with a
      stenosis, 3 at the T tube insertion site), 9 biliary stenosis, 3 papillary
      stenosis, 2 biliary aggregates and one case of ischemic type biliary lesion,
      resulting in an overall complication rate of 30%. 10 (36%) "bc" could be treated
      successfully endoscopically, whereas 8 (32%) patients are still under observation
      with an endoprosthesis in the biliary tract. 10 endoscopic trials were without
      the desired effect, requiring a surgical reintervention. In 4 cases a thrombosis
      of the hepatic artery was responsible for the unwanted course.

PMID- 11824257
TI  - [Psychosomatic selection of living liver donors].
AB  - In the Essen University Clinic for Psychotherapy and Psychosomatics, between
      January and December 2000, 54 potential liver donors and 12 kidney donors were
      examined. All the kidney donors were found to be suitable; 7 potential liver
      donors were rejected on psychosomatic grounds. Reasons for the rejection were
      addiction (1 donor), suspected financial dependency of the donor on the recipient
      (1 donor) and, in the case of one donor not related to the recipient, the
      apparent lack of a special emotional attachment. During the actual evaluation
      interview, 4 potential donors reversed their original decision. Such a
      psychosomatic evaluation is a great help for donors in clarifying their motives
      and their decision.

PMID- 11824258
TI  - [Progress in transplantation surgery--current status: kidney transplantation,
      recurrence of the primary illness and kidney transplantation].
AB  - Although there are numerous reasons for organ loss following transplantation, the
      recurrence of underlying disease plays a major role. Focal segmental
      glomerulosclerosis and mesangioproliferative glomerulonephritis are leading
      causes. Especially in children, hemolytic uremic syndrome (HUS) is a wide
      concern. If recurrence occurs, there is a high chance of graft loss within the
      next one to two years. Therapeutic options are minimal and focus on symptomatic
      relief of the ongoing vascular processes. Only metabolic causes may be treated by
      a combined transplantation, e.g., kidney plus liver in oxalosis and kidney plus
      pancreas in diabetes mellitus. Prospective therapeutic studies are required to
      solve part of the problem.

PMID- 11824259
TI  - [Supportive sepsis therapy: what is still valid today?].
AB  - Following several disappointing approaches to decrease the mortality of septic
      patients using various adjuncts, protein C is the first substance leading to a
      significant reduction of the mortality rate (PROWESS). The increased risk for
      bleeding complications in patients receiving protein C, however, limits its use
      in septic surgical patients. Administration of AT III in septic patients
      (KYBERSEPT) reduced the mortality rate solely in patients which were not treated
      with heparin. Although hydrocortisone reduced the amount of vasoactive
      katecholamines the effect of hydrocortisone administration on the survival rate
      remains unknown. In summary, early intervention to eliminate the septic focus and
      the use of antibiotics according to an antibiogramm still remains the most
      efficient basis for the treatment of septic patients.

PMID- 11824260
TI  - [Laparoscopic emergency surgery in perforated gastroduodenal ulcers].
AB  - The value of laparoscopic treatment of perforated gastroduodenal ulcers remains
      to be determined. To evaluate this modality the results of laparoscopic treatment
      of 18 patients with perforated gastroduodenal ulcers were compared with 28
      patients who were operated by open access. Patients operated on conventionally
      had a mean ASA score of 2.9 compared to 1.8 in the laparoscopic group (p =
      0.0009). Operative time revealed no difference between both groups, no patient
      had to be converted. Morbidity and mortality was 16.7% (3/18) and 0% in the
      laparoscopic group compared to 10.7% (3/28) and 35.7% (10/28) in the open group
      (p = 0.41 and p = 0.19). The mean postoperative hospital stay was 9.4 compared to
      15.3 days (p = 0.15). The laparoscopic treatment of perforated gastrointestinal
      ulcers is an effective method, which can be used in suited patients with a low
      morbidity and mortality.

PMID- 11824261
TI  - [Endoscopic therapy of peptic ulcer hemorrhage--is there still an indication for
      surgery?].

PMID- 11824262
TI  - [Anastomotic insufficiencies of the esophagus--early surgical endoscopy and
      endoscopic therapy].
AB  - Therapeutic value of flexible endoscopy regarding treatment of esophagoenteric
      anastomotic leakage was retrospectively analyzed in 56 patients (female n = 13,
      male n = 43, age 60 years, 1/1992-4/2000). Endoscopic treatment was performed in
      44 patients (self-expanding metal stent n = 38, fibrin glue n = 16, feeding
      tube/decompression tube n = 20, endoscopic percutaneous jejunostomy n = 8),
      interventional radiological technique in 4 patients and surgical treatment in 11
      patients. All patients with open surgical reintervention developed
      reinsufficiency of the anastomosis. Successful endoscopic therapy was achieved in
      75% with a mortality of 21.4%. Endoscopic treatment of esophageal anastomotic
      insufficiency is an effective alternative to conventional re-thoracotomy. The
      appropriate endoscopic intervention needs to be decided individually depending on
      diagnosis and location.

PMID- 11824263
TI  - [Infected necroses and pancreatic abscess: surgical therapy].
AB  - Infected pancreatic necrosis and pancreatic abscesses are severe complications of
      necrotizing pancreatitis. Compared to infected necrosis, pancreatic abscess is
      associated with lower mortality. Surgical treatment is the current standard.
      Necrosectomy is performed as a single-step operation in combination with
      postoperative drainage/lavage or as scheduled reoperation. In selected cases,
      pancreatic abscesses can be successfully drained by percutaneous interventional
      drainage. Mortality in infected necrosis is 20-30% and 5-10% in patients with
      pancreatic abscess.

PMID- 11824264
TI  - [Conventional surgery in peptic ulcer perforation: indications and procedure].
AB  - Open surgery of ulcer perforation still represents the treatment of choice in
      2001. This procedure allows a safe approach to the ulcer site and exact excision
      of the border of the ulcer in order to reach tissue with good vascularisation. In
      pre-, intra- and post pyloric ulcer perforation the gastric outlet can be
      palpated after suturing in order to avoid stenosis. In gastric outlet obstruction
      or large perforated ulcers gastric resection can be performed. Open surgery
      allows an exact lavage of all quadrants of the abdomen in order to remove all
      sequelae of peritonitis. According to the current study laparoscopic procedures
      have no advantages compared to open surgery for ulcer perforation. Conservative
      treatment includes the risk of safety of diagnosis and difficulties in the
      continuous clinical monitoring as well as significant disadvantages in case of
      delayed laparotomy.

PMID- 11824265
TI  - [Course of illness in acute pancreatitis].
AB  - The incidence of acute pancreatitis per year is estimated to be between 10 and 46
      per 100,000 population. The mortality rate of acute edematous pancreatitis is
      below 1%, whereas patients suffering from hemorrhagic-necrotizing pancreatitis
      die in 10-24% of cases. In 80% acute pancreatitis is caused by either gallstone
      disease or excessive alcohol consumption. As of today no specific therapy has
      been developed for the treatment for acute pancreatitis. Acute pancreatitis is
      characterized by specific clinical and morphological alterations that occur in a
      time dependent manner. Frequently occurring complications are parenchymal
      necrosis (15-25%), multiorgan failure (10-26%), pancreatic pseudocysts (5-15%),
      recurrence of pancreatitis (21%) endocrine (6.5%) and exocrine (13-27%)
      insufficiency and a transition to chronic pancreatitis (10-25%).

PMID- 11824266
TI  - [Treatment strategy in iatrogenic perforation of the large intestine].
AB  - Iatrogenic perforation of the colon is a rare but feared complication of
      coloscopy with an incidence of up to 0.3%. During a period of 12 years we saw 14
      perforations of this kind. The therapeutic approach varies with the state of
      peritonitis and type of perforation. Conservative primary therapy should only be
      chosen in rare cases. Classic operative therapy ranges from simple suturing to
      partial resection of the colon, in cases including even formation of a colostomy.
      In case of diffuse peritonitis discontinuity resection following Hartmann is
      still recognized as a secure procedure. Lethality of 7.1% in our own patients
      confirms the effectivity of conventional operating methods.

PMID- 11824267
TI  - [Radiological acute diagnosis in suspected perforation of the large intestine].
AB  - The last decade has seen changes in imaging procedures in patients with suspected
      colon perforation. Many traditional emergency imaging techniques have been
      replaced with helical CT, that can be performed with great accuracy, less patient
      discomfort and, probably, decreased cost. Because CT is more sensitive than
      conventional radiography in identifying subtle pneumoperitoneum, helical CT is
      ideally suited for rapid evaluation of the abdomen for patients with acute pain
      from suspected perforation. CT is often indicated when free air is seen at
      conventional radiography but perforation site is not clear. It is also indicated
      when air is strongly suspected despite normal abdominal radiographic findings.

PMID- 11824269
TI  - [Differential surgical therapy in hemorrhoids].
AB  - Haemorrhoids 3 degrees should be treated operatively. In segmental lesions,
      excisional haemorrhoidectomy (Milligan-Morgan, Ferguson, Parks) is the procedure
      of choice. For more circular haemorrhoidal piles, circular stapled
      haemorrhoidectomy has been used in Germany since 1998. In cases of additional
      prolapsing anoderm reconstructive anoplasty might be superior. Using a
      classification orientated therapeutical regime for haemorrhoidal disease offers
      high healing rates with a low rate of complications and recurrences.

PMID- 11824268
TI  - [Acute and perforated sigmoid diverticulitis. Surgical indication: single stage
      versus multiple-stage operation].
AB  - The indication and the optimal surgical procedure of complicated diverticulitis
      are still under discussion. The choice of the surgical therapy has its highest
      priority in the cure of the infection by sigmoid resection. Resection with
      primary anastomosis can be done in cases of covered perforation (Hinchey 1 + 2)
      with a low mortality. Diffuse peritonitis should be treated depending on the
      individual local situation.

PMID- 11824270
TI  - [Endoscopic treatment of bile leakage after laparoscopic cholecystectomy].
AB  - INTRODUCTION: Bile leaks are typical complications following LCHE. By ERC
      localisation and nature of the leak can be documented and therapy is possible in
      the same session. The aim is reduction of intraluminal bile pressure. PATIENTS
      AND METHODS: 1799 LCHE were followed by 34 bile leaks. 2 common duct injuries and
      a duodenal perforation had surgical revisions. 31 patients had endoscopic therapy
      only (stent +/- EST). Bile secretion stopped 3.2 days later.
      Stentextraction/documentation of closure of the fistula 7 weeks later.
      COMPLICATION/LETHALITY: 1 Stentdislocation. Lethality: 0. CONCLUSION: ERC allows
      diagnosis and therapy of bile leaks by common duct stenting. Laparoscopic or
      surgical reintervention is not necessary.

PMID- 11824271
TI  - [Conservative therapy of incontinence].
AB  - Conservative therapy of faecal incontinence includes normalisation of colonic
      function, restauration of damaged anal skin and exercising methods. The most
      successful of those seems to be Biofeedback with good short time results up to
      92% patients without further complaints, the long time results still being up to
      67%. Prognosis depends on neuropathy, age and ability of perception and
      compliance. Passive electrostimulation replaces the damaged nerve and therefore
      has to be done lifelong. Increasing anal resting pressure seems to be a possible
      result.

PMID- 11824272
TI  - [Stage-adjusted therapy of hemorrhoids--ambulatory or inpatient treatment?].
AB  - The aim of the therapy of piles is to cure the complaints of the patient by
      reducing the enlarged haemorrhoidal plexus according to the stage (1 degree to 3
      degrees) to a nearly physiological size and in case of a prolapse to replace the
      sensitive anoderma. The basic therapy consists of regulating the bowel function
      and avoiding straining. A high fibre diet or bulk laxatives may be necessary. If
      this fails 1 degree haemorrhoids should be treated in the office by
      sklerotherapy, 2nd or 2nd to 3rd degree haemorrhoids by rubber band ligation from
      the very beginning. The Haemorrhoidal Artery Ligation (HAL) and the circular
      mucosectomy with a stapling device can be done as an office procedure too. An
      anal prolapse of 1 or 2 segments should be treated as outpatient surgery in an
      "open" technique (Milligan-Morgan), more than 2 segments in a "closed" (Ferguson)
      or better in a "semi-closed submucosal" technique (Parks) in the hospital. A
      cicular anoplasty preserves the anoderma and enables its reposition as well as
      the excision of perianal skin tags and fibromata. This is not an office
      procedure.

PMID- 11824273
TI  - [Postoperative complications--what is often? What is rare?].
AB  - The postoperative course after major (elective) digestive surgical procedures was
      prospectively analysed in 5693 patients. Postoperative complications were
      documented in 553 patients (9.7%). There were general complications (not related
      to surgery) in 97 patients (17.5%) and surgical complications (related to
      surgery) in 456 patients (82.5%). The most frequent surgical complication was
      abdominal sepsis in 72.1% followed by postoperative bleeding (17.1%) and others
      (10.7%). The leading cause for abdominal sepsis was anastomotic leakage in 207
      patients (70.2%). Bedside diagnostic procedures like sonography, analysis of
      fluid drainage and endoscopy could identify the underlying problem of abdominal
      sepsis in 60.9% of cases. The mortality rate of all studied patients was
      (113/5693 patients) 1.9%.

PMID- 11824274
TI  - [Intensive care management of ARDS].
AB  - The acute respiratory distress syndrome (ARDS) is characterized by (1)
      intrapulmonary right-to-left shunting, (2) permeability edema of the lung, and
      (3) alterations in pulmonary compliance. The clinical features of ARDS are due to
      an acute inflammatory reaction of the lung. Current clinical management of
      patients with ARDS aim at implementation of lung protective ventilatory
      strategies with adequate PEEP and low tidal volumes, diagnosis and treatment of
      underlying infections, and a negative fluid balance together with positional
      maneuvers like prone positioning.

PMID- 11824275
TI  - [Emergency diagnosis and emergency care in trauma resuscitation].
AB  - Adequate primary and preclinical evaluation of thoracic trauma is the basic for
      effective therapy. The first intention must be to understand the mechanism of
      trauma and injury. Severe thoracic trauma is predominantly the result of high
      energy trauma and mostly combined to multiple injuries (polytrauma). The
      intention of emergency care medicine is to reduce the number of lethal
      complications due to trauma. Early intubation and ventilation in preclinical
      management is accepted as a gold standard. Nevertheless, there is a high
      percentage of nonintubated and undertreated polytraumatised patients that reach
      the clinic. To investigate the reason for and problems of undertreatment we have
      to initiate basic research in accident and polytrauma research.

PMID- 11824276
TI  - [Arthroscopic shoulder stabilization].
AB  - Beside electro-thermic procedures (ETACS, LACS) several suture-anchor system for
      labrum fixation have been developed in the last years. From 4/96 to 10/00 we
      performed 242 arthroscopic shoulder stabilizations with FASTak-(n = 159) Panalok
      (n = 26) and Suretac suture anchors (n = 57) in our clinic. The patients were re
      examined with a follow-up of at least 12 months. The best results were in the
      FASTak-group. After 2 years 4.7% suffered a redislocation. 28.6% (2 patients)
      needed a revision. The Rowe score was 83.1 +/- 20.9 points. There was a high
      satisfaction of the patients with the operative result and 60.9% could go back to
      their pre-op sports level. Compared to open procedures the arthroscopic shoulder
      stabilization has many advantages. At 24-months follow-up this study demonstrates
      good results of arthroscopic shoulder stabilisation with FASTak suture anchors.

PMID- 11824277
TI  - [A condylar plate in distal femoral fractures].
AB  - Up to the seventies, the surgical treatment of supra- and bicondylar femoral
      fractures was difficult and was accompanied by a lot of complications. In most
      studies conservative treatment was recommended. In the last 30 years the clinical
      outcome after surgical treatment has improved. This was a result of the
      development of new implants and improved surgical techniques. Today, the primary
      surgical treatment is the therapy of choice. We reviewed from 1986 to 2000 105
      distal femoral fractures which in 32 cases were treated with a condylar blade
      plate. The final results were rated using the system that was described by Neer.
      The averaged follow up time was 9 years. Low postoperative infection rates and in
      75% excellent and satisfactory results combined with low cost are the state of
      art which has to be the reference for new methods and new implants in the future.

PMID- 11824279
TI  - [Distal femoral fracture--technical possibilities].
AB  - The fractures of the distal femur are classified as extra-articular fractures
      (type A), partial articular fractures (type B), and complete articular fractures
      (type C). The aims of operative treatment are anatomical reconstruction of the
      articular surfaces, restoration of rotational and axial alignment, stable
      fixation of the condyles to the shaft of the femur and early functional
      aftercare. Techniques and implants for treating intra-articular fractures lies in
      the reduction of the joint fragments and fixation with lag screws. For the
      treatment of the extra-articular fractures different approaches, techniques and
      implants have proven to be reliable and effective: direct-indirect reduction,
      open-minimal invasive approaches, open-slipped techniques. Implants: condylar
      plate, dynamic condylar screw (DCS), condylar buttress plate, anterograde
      nailing, retrograde nailing, internal fixators (Low Invasive Stabilisation System
      -LISS) and external fixation.

PMID- 11824278
TI  - [The DCS plate osteosynthesis of the distal femur].
AB  - The DCS is an implant to be used only in certain situations. It offers solutions
      when the medullar cavity is blocked by implants in the proximal femur, and in
      case of pathological fractures, where it is necessary to remove all cancerous
      tissue and to reinstate the stability of the bone through compound
      osteosynthesis. The DCS is absolutely necessary when there is no possibility to
      reconstruct the condyles with closed procedures and has the advantage of
      anatomical reconstruction. In the case of partly supracondylar fractures, the
      kneepoint is not tampered with, and by subcutaneous technique, the operation is
      less traumatic.

PMID- 11824280
TI  - [LISS--internal plate fixator].
AB  - The LISS DF (less invasive stabilisation system) is a new internal fixator for
      the operative treatment of distal femur fractures following the principles of
      minimally invasive surgery. The fixation of the implant is based on screws
      providing angular stability, which are inserted percutaneously guided by an
      aiming device. A large exposure of the fracture zone is not necessary. Between
      December 1996 and November 1998 a multicentre study were defined including
      finally 112 patients with 116 distal femur fractures treated with a LISS system.
      A follow up rate of 93% could be achieved, showing a fractures consolidation in
      96% of all cases after 12 months. The results of the study showed a low rate of
      secondary bone grafting. The LISS system is a secure device for the treatment of
      all distal femur fractures including complex articular fractures types.

PMID- 11824281
TI  - [Indications criteria for treatment of distal radius fractures].
AB  - To achieve an optimal functional result after distal radius fractures the
      treatment has to orientate at different criteria. The bone destruction must be
      analysed. A fracture classification is necessary to use all the variable
      alternatives of treatment. With the AO classification we are able to describe
      most of the variable fracture types. Soft tissue damage and osteoporosis must be
      regarded additionally. The most important criteria however in fracture treatment
      is the fracture type.

PMID- 11824282
TI  - [Multimodality therapy concepts in esophageal carcinoma].
AB  - The role of preoperative chemotherapy for esophageal cancer still remains
      controversial. Only one study of the recently published, randomized controlled
      trials in potentially resectable esophageal cancer has shown improvement in
      survival by preoperative chemotherapy compared to surgery alone. Nevertheless,
      there has been a consistent observation that in patients who respond to
      preoperative therapy survival was significantly prolonged. Therefore, a
      diagnostic test that allows prediction of response is considered to be crucial
      for the future use of preoperative chemotherapy in patients with esophageal
      cancer. Molecular markers for response prediction and reliable non-invasive
      techniques such as FDG-PET are not yet established. At the moment therefore
      responder should undergo esophagectomy for definitive curative treatment, whereas
      non-responder may undergo individualized salvage therapy.

PMID- 11824283
TI  - [Therapy of acute triquetrum fractures and LT ligament injuries].
AB  - Fractures of the triquetrum: Triquetrum fractures consist of two types: chip
      fractures of the dorsum and fractures of the body of the bone. Dorsal cortical
      fractures respond well to a short time splint or cast support. Non-displaced
      fractures of the body can be treated by immobilization for four to six weeks.
      Displacement of body fractures is very rare and often the result of perilunate
      instability. This condition usually requires open reduction, internal fixation
      and ligament repair. Lunotriquetral ligament injury: Partial lunotriquetral
      ligament disruption and dynamic instability should be treated by immobilization
      alone. Acute complete ligament disruption with static instability results from
      perilunate instability and requires operative treatment with ligament
      reconstruction and joint stabilization with K-wires followed by longer
      immobilization.

PMID- 11824284
TI  - [Functional anatomy and biomechanics of the wrist joint].
AB  - The osteoligamentous guidance of the carpal bones is similar to a ring under
      tension. Axial load of the wrist passes through the radiocarpal compartment of
      the proximal carpal joint on to the forearm. Hand motions in the carpal region
      produce variable changes of bone position. From that many deformities in cases of
      carpal instabilities could be explained.

PMID- 11824285
TI  - [Panaritium of the distal finger joint and subcutaneous infections of the hand].

PMID- 11824286
TI  - [Acute perilunar dislocations: algorithm for treatment].
AB  - In most cases, perilunar dislocations of the wrist are caused by high speed
      accidents. Usually these injuries occur by a fall on the dorsiflexed
      superextension of the hand. The instability caused by injuries of various
      erticular structures (ligament, bone) show various developmental stages. Clinical
      symptoms are reduced and painful movement, instability of the carpus, snapping
      and swelling. The diagnosis is established by X-ray, cinematography, arthrography
      MRT or CT. Perilunar instability with or without associated fractures and
      particularly de Quervain must be reduced and treated operatively including suture
      of the ligament and stabilization of the fracture.

PMID- 11824287
TI  - [Penetrating injuries of the rectum and anus: primary management, reconstruction,
      rehabilitation].
AB  - In adults direct trauma to the anus and rectum originates mostly from gun shots,
      road traffic accidents, autoeroticism or sexual abuse. Real "impalement" injuries
      have been frequently seen only in children. As in any polytraumatized patient
      primary diagnostic procedure--after adequate resuscitation of the patient-
      consists of X-ray and ultrasound. The patient should be examined in the OR under
      general anaesthesia and placed in lithotomy position. Treatment often requires a
      multidisciplinary approach. Primary surgical therapy consists of 4 D's:
      debridement, drainage, diversion and distal irrigation. No primary reconstructive
      surgery should be tried. After recovery of the patient dedicated functional
      testing has do be done prior to reconstructive measures which include sphincter
      reconstruction. With this concept mortality is low, but functional outcome is
      variable.

PMID- 11824288
TI  - [Management of thoracic trauma in multiple injuries in the clinic].
AB  - Injuries to the chest and lung are common in the polytraumatized patient.
      Clinical series have shown that on average 20% of all deaths following a
      polytrauma are caused by a chest trauma. The most common chest injuries are rip-
      and serial rip fractures with an unstable chest as well as pneumo- and
      hematothorax. Further common injuries to the lung parenchyma are lung contusions,
      lacerations and lung hematoma. The clinical outcome of chest injuries is closely
      related on a clear treatment strategy, with a sufficient preclinical assessment
      and early intubation, early temporary or definitive fracture stabilisation and
      implementation of intensive care and lung protective treatment rules.

PMID- 11824289
TI  - [Gene therapy--therapeutic option in treatment of chronic wounds?].
AB  - Chronic wounds seem to be a severe problem in terms of socioeconomical meanings
      due to the fact, that the average age of patients suffering from these wounds
      rises steadily. Therapy of chronic wounds is complicated and oftenly not
      satisfying. Even application of local growth factors according to the latest
      findings in terms of cell and molecular regulatory mechanisms during wound
      healing does not lead to success because of the immediate inactivation of these
      growth factors in the wound fluid of chronical wounds. Knowing these facts one
      has to ask if new developments like genetical modification of cells participating
      in wound healing may lead to sufficient results in the therapy of chronical
      wounds.

PMID- 11824290
TI  - [Indications for intramedullary stabilization of shaft fractures in childhood.
      What is reliable, what is assumption?].
AB  - For some 15 years the elastically stable medullary nailing (ESIN) has been used
      in fracture treatment in children. The group of Nancy (Prevot and colleagues)
      first described the procedure for shaft fractures in children. Now the method is
      the standard procedure for stabilisation of long bone diaphyseal and metaphyseal
      fractures. During recent years a number of papers have described good and
      excellent results with this method, especially for shaft fractures of femur and
      forearm. In some papers there are also methods for articular fractures in more
      demanding techniques presented. Also when we have no evidence-based studies, we
      can say from the experience out of the last years that the ESIN is a biological,
      minimally invasive fracture treatment to achieve a high level of reduction and
      stabilisation in fractures in children. The use of titanium nails leeds to a
      higher rate of flexural elasticity and so the titanium nails are more recommended
      for this method.

PMID- 11824291
TI  - [Complications and errors in use of intramedullary nailing in shaft fractures in
      childhood].
AB  - Elastic stable intramedullary nailing (ESIN) is well established for stabilizing
      pediatric diaphyseal fractures. Indications are all femur shaft and instable
      diaphyseal forearm fractures, selected instable lower leg and malaligned humerus
      fractures. Intraoperative problems (6.5%) include the need for open reduction,
      cortical perforation by a nail tip and bursting of a third fragment.
      Postoperative problems (6.4%) are mainly induced by skin irritation at the place
      of implantation. Complications (8.4%) result from wrong indication with
      subsequent malalignment and instability. Re-fractures are seldom seen. Typical
      iatrogenic nerve injuries (superficial radial nerve) need technical variation.
      Prevention of most complications and mistakes requires the exact consideration of
      guidelines for indication and technique even in a supposed easy procedure.

PMID- 11824292
TI  - [What is a hemangioma, what is a malformations? On the differential diagnosis of
      vascular tumors].
AB  - Systematic and diagnostic classification is important with regard to a carefully
      directed therapy. Difficulties emerge from the necessary combination of different
      categories (e.g. location, morphology, etiology). A major consideration is the
      difference between dilatation (ectasia) and proliferation. We have to distinguish
      between connatal teleangiectatic nevi (deficient neurovasal transfer), tardive
      angiectatic nevi (deficient capillary walls) acquired vascular damages,
      angiokeratotic nevi, lymphectatic nevi, angiomas (primary vascular
      proliferation), glomangiomas, and malignant vascular tumors.

PMID- 11824293
TI  - [Progress in oncological visceral surgery--esophageal carcinoma].
AB  - Compared to adenocarcinoma of the esophagus (Barrett cancer) the prevalence of
      esophageal squamous cell cancer is decreasing. Patients with squamous cell cancer
      have a less favorable risk profile for surgical therapy, a higher prevalence of
      lymphatic spread in early tumor stages, and more frequently an invasion of
      lymphatic vessels (lymphangiosis carcinomatosa) than patients with
      adenocarcinoma. A transthoracic en-bloc esophagectomy is therefore the procedure
      of choice for squamous cell esophageal cancer. The prognosis after surgical
      resection is worse for squamous cell esophageal cancer as compared to
      adenocarcinoma. In patients with early Barrett cancer a limited surgical approach
      is possible. The results of radical transmediastinal esophagectomy compare
      favorably to transthoracic esophagectomy in patients with locoregional Barrett
      cancer.

PMID- 11824294
TI  - Endoscopic thoracic sympathectomy in the treatment of functional microangiopathy
      of the upper limb.

PMID- 11824295
TI  - [Endovascular (transfemoral endoluminal aneurysm management; TEAM) versus
      conventional open therapy in abdominal aortic aneurysms (AAA): analysis of a
      clinical series].
AB  - All patients (n = 826) treated electively at the Department of Vascular Surgery
      University of Vienna, Austria, for their AAA during the years 1965-2000 were
      analysed with particular emphasis on endoluminal repair. Data collection was
      carried out in retrospect. The operative mortality or within 30 days was
      considered the primary endpoint of the study. Since 1995 the TEAM approach was
      available. From that point in time 45.5% of the AAA were treated electively in
      the endoluminal way. An exploratory analysis of the clinical series revealed a
      statistically significant difference in the incidence of various risk factors
      between groups in favor of open repair. Consequently a conditional regression
      analysis demonstrated the operative method, median patient's age (above versus
      below 72 years of age), reduced renal and/or pulmonary function to be of
      significant influence.

PMID- 11824296
TI  - [Preoperative risk factors as deciding criteria in surgical treatment strategy of
      infrarenal aortic aneurysm].
AB  - Significant risk factors of operative therapy in patients with infrarenal aortic
      aneurysms (AAA) were determined. Best treatment strategy (open surgical repair,
      transluminal endovascular aneurysm management (TEAM) or conservative treatment)
      was selected on the base of evaluated risk factors, tendency of rupture and life
      expectancy. Of the typical risk factors impaired renal and/or lung function
      showed a significant influence on hospital mortality. In patients without these
      significant risk factors open surgical repair leads to good clinical results.
      Acceptable postoperative mortality rates after elective exclusion of an AAA with
      average size in patients presenting significant comorbidities can only be
      achieved using TEAM. If TEAM can not be performed, open surgery is only justified
      in the case of very large AAA diameter.

PMID- 11824297
TI  - [Influence of etiology and morphology of traumatic vascular injuries on outcome,
      risk of amputation and mortality].
AB  - In a retrospective trial 159 vascular injuries in 149 patients were registered
      between 1987-1996. Extremity vessels were injured in 76% of the cases. The same
      incidence was observed in blunt and penetrating mechanisms. Blunt vascular
      injuries were associated with an higher rate of live threatening organ damage,
      longer times of ischaemia (6.5 versus 3.0 h) and an higher mortality (9.7 versus
      20.3%) than penetrating injuries. We have found an increased mortality rate in
      all cases with concomitant trauma of CNS, chest, abdomen or bones. The overall
      amputation rate in all peripheral vascular injuries has been 22.6%. The
      functional outcome has been reduced by nerve lesions, amputation and the sequelae
      of fractures.

PMID- 11824298
TI  - [Late outcome after management of vascular injuries].
AB  - Long-term results of vascular repair in patients with trauma are influenced by
      diagnosis and therapy in the acute stage. Reconstructions of major venous or
      arterial injuries of the extremities demonstrate a higher rate of early occlusion
      compared with the follow-up period. The optimal management of major venous
      injuries remains controversial, however, there is a tendency to vascular repair
      whenever it can performed safely. Venous repair of the complex type is associated
      with a higher rate of early occlusion. The patency rate of arterial
      reconstructions after vascular trauma is even more than 90% in most cases with a
      large proportion of fully functional limbs. Endovascular treatment of acute
      vascular trauma may increase, however, there are only a few cases demonstrating
      long-term results.

PMID- 11824299
TI  - [Injuries of the thoracic blood vessels--diagnosis and therapy].
AB  - Thoracic vascular trauma is divided into perforating and nonperforating injuries.
      Patients with perforating lesions with median sternotomy has to be performed if
      circulation is still functioning marginally. In a severe hemorrhagic shock it can
      be necessary to do an immediate emergency lateral thoracotomy. Trauma of the
      thoracic aorta occurs most frequently as a consequence of blunt injury as a
      result of decelerate or crushing. Fewer than 20% of patients with thoracic aortic
      injury survive the initial insult. Additionally the survival depends on severity
      of associated injuries. This means that the timing of surgical intervention in
      the stable, covered aortic rupture with serious associated injuries should
      preferably be deferred until the patients condition is stabilized. Emergency
      operation has to be performed in case of symptomatic transaction in the
      hemodynamic unstable condition including simultaneous surgery of concomitant
      lesions. Paraplegia remains the most deleterious problem. Endovascular stents are
      used increasingly to treat traumatic rupture of the aorta.

PMID- 11824300
TI  - [Vascular biological aspects of thrombendarterectomy and alloplastic vascular
      replacement].
AB  - Irrespective of vascular approach and mode of repair any arterial reconstruction
      is charged by a procedural trauma and a desintegration of the vascular wall in
      its pathoanatomic structure. A number of specific repair mechanisms are set in
      motion by cellular and humoral mediators when non-endothelial layers get exposed
      to the lumen. Platelet deposition, local activation of hemostatic factors,
      intramural and wall-adjacent thrombus formation as well as subsequent
      proliferation of myofibroblasts are determinants of this process that may be
      characterized as a generalized wound healing response resulting in neointima
      formation. Exemplarily, the valency of endarterectomy and prosthetic grafting in
      the femoral axis is discussed on the background of recent experience in vascular
      biology.

PMID- 11824301
TI  - [Late complications after alloplastic vascular replacement].
AB  - The follow-up of 273 AAA patients operated 1981-1985 showed a mean dilation of
      polyester grafts of 17.4% in 12 days and 34.8% in 3 years. This early dilation is
      due to mesh expansion of the warp knitted grafts. It has no clinical relevance.
      In contrary the late dilation after approximately 10 years is due to degradation.
      The evaluation of 436 explanted grafts attained from 75 hospitals showed graft
      rupture to be the cause of the explanation for 42/255 (16%) polyester grafts and
      2/42 (5%) PTFE grafts. The most ruptures were observed in the surrounding of the
      inguinal ligament after 10 to 20 years of duration. In comparison to modern
      endovascular grafts the conventional polyester and PTFE grafts still are the gold
      standard of durability.

PMID- 11824303
TI  - [Endovascular therapy in pelvic vein spur].
AB  - Treatment of pelvic vein spur is indicated in patients suffering from severe leg
      swelling and pain as well as after thrombectomy or lysis of spur-related deep
      vein thrombosis (DVT). In symptomatic patients without accompanying DVT,
      secondary patency amounted to 100% after 2 years when the spur was dilated and a
      self-expanding stent was implanted. In cases with successfully reopened pelvic
      veins after spur-induced DVT and stent application, the corresponding figure was
      82%. Endovascular therapy of pelvic vein spur represents a safe and effective
      treatment modality. Because of its less invasive nature compared to open surgery,
      stent implantation has to be considered the method of first choice.

PMID- 11824302
TI  - [Combination therapy of venous thrombosis with local thrombolysis and surgical
      thrombectomy].
AB  - Combination therapy in acute deep venous thrombosis essentially consists of a
      highly dosed locoregional thrombolysis of the valve carrying crurofemoral axis
      and a mechanical thrombectomy of the valveless pelvic axis by Fogarty catheter.
      The success of this method is due to the fact that it largely eliminates the
      disadvantages of systemic thrombolysis as well as conventional surgical
      thrombectomy whilst retaining the advantages. Using combination therapy within
      the first 7 days in acute leg and pelvic venous thrombosis can result in restutio
      ad integrum, i.e. complete desobliteration with maintained valve function (more
      than 80% of cases).

PMID- 11824304
TI  - [What is the difference between ambulatory care and inpatient varicose vein
      patients?].
AB  - The operation of varicose veins seems to be safe and simple. Nevertheless,
      serious complications are possible requiring skill and experience in vascular
      surgery. A clinical treatment in these cases ist mandatory. Also extensive
      varicose veins and cases with comorbidity have to be operated in the hospital.
      Outpatient treatment is often less extensive and not sufficient ("quicker and
      sicker") and for that not cheaper than a clinical stay. Therefore operative
      treatment during a hospital stay must be possible even in times with shortness
      for money as regulated in the guidelines of the German Society for Vascular
      Surgery.

PMID- 11824305
TI  - [Venous bypass: gold standard with excellent results].
AB  - Since 1974 we have performed 1104 in situ vein bypasses for the reconstruction of
      femoropopliteal or femorotibial occlusions. The venous valves were made
      incompetent by using our Insitucut. An intraoperative completion angiography is
      mandatory. The primary cumulative patency rate is 93.5% at one year and 64.9% at
      five years. The permeability is depending on the quality of the outflow tract.
      The patency of femoropopliteal in situ bypasses with a three vessel runoff is
      82.2% at five years, whereas bypasses with a single vessel runoff show a patency
      of 56%. The own results are comparable with the results of reversed and non
      reversed vein bypasses given in the literature.

PMID- 11824306
TI  - [Early diagnosis and therapy of deep venous thrombosis with 111 indium labeled
      platelets].
AB  - Clinical assessment of platelet scintigraphy by using autologous platelet labeled
      with 111-indium oxine to detect thrombotic activity for deep vein thrombosis.
      Platelet accumulation on scintigrams had a tendency to correlate with aggravation
      of acute thrombotic symptoms in deep vein thrombosis. This method was a useful
      procedure to make early diagnosis of deep vein thrombosis by detecting of
      abnormal accumulation of platelet. In addition, appropriate thrombolytic and
      anticoagulant therapy resulted in reduced platelet accumulation in conjunction
      with improvement of acute clinical symptoms. Thus, platelet scintigraphy could be
      available to evaluate thrombotic activity and might be useful for determining the
      optimal indications of thrombolytic and anticoagulation therapies for acute deep
      vein thrombosis. On the other hand, another kind of scintigraphy might be
      inevitable especially for detection of the pulmonary embolism. Anticoagulation
      therapy is also effective for pulmonary embolism.

PMID- 11824307
TI  - [Lymphangioma colli--what are the prognostic factors? Experiences with 36 cases].
AB  - AIM: A new classification of the Lymphangioma colli (LC) should allow to inform
      about prognosis at the time of diagnosis or prenatal sonography. METHODS: Pre-
      and postoperative parameters in 36 operated children (1988-2000, O follow up 4.3
      years) were evaluated dependent on the volume of the LC as defined. Type I: the
      tumor does not alter the normal shape of the neck; type II: the LC reaches a line
      placed at the lateral border of the head; type III: the LC does not respect this
      line; type IV: the LC exceeds the midline of the body. RESULTS: According to
      delivery, diagnostics, resection, reintervention, postoperative complications,
      nerve injury, hospital stay, aesthetics, tracheo- and gastrostoma predominantly
      significant differences were found. CONCLUSIONS: The proposed classification
      permits to advise the parents about the expected prognosis: Type I: it is
      excellent; type II: some asymmetry remains in 15%; type III: postoperative
      complications occur in up to 38%; type IV: morbidity increases and prognosis
      decreases significantly.

PMID- 11824308
TI  - [Surgical correction of vascular malformations of the lower extremity].
AB  - On the basis of the Hamburg Classification from 1988 six different therapeutic
      tactics and surgical techniques have been proved in the treatment of vascular
      malformations. These are: 1) reconstructive surgery, 2) surgery to reduce the
      hemodynamic activity of the vascular defect, 3) surgery to extirpate the
      malformed vessels, 4) combined therapy, 5) unconventional therapy, 6)
      multidisciplinary treatment. More than 2500 cases had been worked out. In this
      survey the marginal vein and the embryonal vein respectively are of special
      interest. These veins are classified by morphologic radiologic criteria. The
      following types could be worked out: peripheral type, thigh type and pelvic type.
      Referring to these experiences the indications for vascular surgical treatment
      have to be distinguished precisely. In a retrospective European study the long
      follow-up results of all six therapeutic tactics had been registered and proved.
      1378 cases were included. In 15% of the patients the results were excellent in
      42% good, and in 34% an improvement could be observed. In 5% a relapse was stated
      and in 1.5% no change was registered.

PMID- 11824309
TI  - [Multimodality therapy concepts in stomach carcinoma].
AB  - The prognosis of gastric cancer is still poor even after curative R0 resection.
      Therefore, among various multimodality treatments a lot of phase II/III studies
      have been carried out evaluating preoperative chemotherapy. Although some
      positive results have been obtained after this procedure, neoadjuvant
      chemotherapy is still an experimental approach. In the future the prediction and
      evaluation of response must be defined more exactly. Using intraoperative radio-
      or intraperitoneal (hyperthermal) chemotherapy reduction of regional relapse or
      peritoneal carcinomatosis could be obtained without increased survival in
      general. According to experience in Japan adjuvant (immuno-)chemotherapy can
      increase the overall survival rates and even in the Western hemisphere some
      actual studies with adjuvant chemo- +/- radiotherapy could demonstrate a benefit
      of survival in patients with lymph node metastases. Nevertheless, multimodality
      treatment strategies must be investigated in further uniform prospective study
      protocols.

PMID- 11824310
TI  - [Systemic therapy of hemangioma].
AB  - For life-threatening hemangiomas where surgical or laser techniques are not
      feasible, systemic therapy with cortisone or interferon represents the therapy of
      choice. With response rates of 80-90%, both drugs are equally effective. Both
      treatments, however, might be associated with severe side-effects. Among these
      the risk of interferon-induced neurotoxicity has to be given special mention.
      Thus, the indication for systemic therapy of hemangiomas has to be made
      carefully, weighing up risk and benefit.

PMID- 11824312
TI  - [Facial reconstruction with microsurgical tissue transfer].
AB  - Although regional flaps are the first choice for face reconstructions, large
      defects require tissue transfer from other parts of the body. Pedicled
      musculocutaneous flaps or free flaps are then the choice. Retrospective analysis
      of our cases of 42 pedicled and 58 free flaps between 1990 and 1999 showed a
      lower complication rate for free flaps. Moreover, free flaps offer the
      possibility of choosing from a variety of flap types, including thin
      fasciocutaneous perforator flaps, bulky musculocutaneous flaps and composite
      flaps with vascularized bone. Complex reconstructions of the face may require
      chimera and prefabricated flaps. Our choice then is the scapular region, where
      the subscapular vessels can carry independent tissue blocks of skin, bone and
      muscle. We demonstrate the reconstruction of the nose, palate and alveolar crest
      of the maxilla with such a prefabricated chimera flap.

PMID- 11824311
TI  - [Differential therapy of hemangiomas--when cryotherapy, laser therapy or
      operation?].
AB  - Hemangiomas are the most common soft tissue tumours in childhood, which arise
      after birth, grow for several months and regress spontaneously. Serious problems
      can occur with closure of the eye resulting in amblyopia or with psychologica
      problems due to disfiguring of the face. Therapeutic possibilities are cryo
      therapy, laser therapy and surgical removal. Cryotherapy can be used for small
      and flat hemangiomas. Bigger hemangiomas are treated with the Nd-YAG laser. Its
      effect is an acceleration of involution. Typical residues of hemangiomas must be
      secondarily corrected surgically. Indications for primary surgical therapy are
      hemangiomas of the eye lid and in the scalp.

PMID- 11824313
TI  - [Plastic surgery coverage in the dorsal trunk area].
AB  - Defects of the trunk are major plastic surgical challenges. In the posterior
      trunk these defects are congenital or acquired. Most of the defects are due to
      major tumor resections, rarely after trauma or burns. With regional or local
      flaps most of the defects can be covered adequately. Presently musculocutaneous
      and perforator flaps are favoured. An interdisciplinary cooperation is mandatory
      for a successful result.

PMID- 11824314
TI  - [Abdominal wall defects caused by postoperative infections].
AB  - Infectious defects of the abdominal wall often result from deeper subfascial
      infections of the abdominal wall caused by a persisting intraabdominal
      inflammation or the result of laparotomy in peritonitis. Therapies applied are
      first of all the removal of the sources of infection and a careful debridement of
      the abdominal wall. There are several ways of temporarily covering the abdominal
      wall, but there is no ingenious solution. In our own experience the application
      of zip fastening and PGS nets have proved successful. In case of deeper
      infections of the abdominal wall the most awkward situation is the laying open of
      small intestine loops in a granulating wound which may lead to a revitalization
      of chronic small intestine fistulae. In these cases a differentiated and repeated
      surgical approach and extensive resection of small intestine parts, and
      consequently a high rate of complications and lethality cannot be avoided.
      Extensive defects of the abdominal wall exposing parts of small intestines after
      such operations require temporary covering and in this case we use Vypro net
      which, under the most favourable circumstances, can represent a final solution.

PMID- 11824315
TI  - [Drainage technique in thoracic trauma and pneumothorax].
AB  - In most cases of perforating thoracic injury, thoracotomy is performed
      immediately. In blunt thoracic trauma with pneumothorax, the drain--24-32 Ch--is
      inserted via a minithoracotomy on the anterior/intermediate axillary line in the
      fifth intercostal space. In spontaneous pneumothorax, a trocar is inserted at the
      same site and the lung inspected thorascopically for so-called ELCs. The drain-
      in this case 24 Ch--is then directed dorsally into the dome of the pleura, this
      being essential for optimal evacuation of air and secretion. So-called
      Pleuracaths are unsuitable because they are 50% coated with fibrin. Drainage on
      the medioclavicular line in the second or third intercostal space is
      inappropriate for various reasons. Emergency management of tension pneumothorax
      comprises pressure relief via a cannula.

PMID- 11824316
TI  - [Injuries of the heart--diagnosis and therapy].
AB  - Injuries of the heart are present in 7-12% of all thoracic trauma cases. Most of
      these (80%) are polytrauma patients. The mechanism of the accident, the
      localisation of injuries, the physical condition of the patients and the skills
      of the hospital stuff are determinant factors for the outcome. Hemodynamic
      instability needs an urgent echocardiography, signs of an obstructive pericardial
      hematoma and/or progressive bleeding require an urgent operation using a left
      lateral or mediosternal approach. ECC and cell saving should be available. The
      contusion of the heart is monitored by ECG and Troponin tests. The application of
      a "mini" heart-lung machine in difficult situations could be very useful.

PMID- 11824317
TI  - [Overview of the relevant aspects of the blood coagulation system--focus and
      cardiovascular hemostasis].
AB  - The hemostasis is a complex regulated system. It can be subdivided into the
      coagulation cascade, the fibrinolytic system, thrombocytes and cellular
      hemostasis. In atherosclerosis there are several systemic changes of the
      hemostasis and fibrinolysis, especially in diabetics. These alterations are
      markedly pronounced in patients with acute complications like acute coronary
      syndromes. The alterations in these patients constitute a prothrombotic state. To
      treat this procoagulant situation several drugs like antithrombins, antiplatelet
      drugs including glycoprotein IIb/IIIa-receptor antagonists, and others are used.
      This therapy itself can cause perioperative hemostatic disorders. Therefore, a
      close communication between cardiologist and cardiac surgeon is necessary to
      handle this complex situation.

PMID- 11824318
TI  - [Morphological changes after lung trauma].
AB  - Post traumatic pleuro-pulmonary lesions can be divided into 3 phases: Acute phase
      I--several days to one week--with superficial pleuro-pulmonary defects as a main
      cause for pneumo-hematothorax, intrapulmonary hematoma from rhexis bleeding of
      parenchymal vessels, tearing of bronchi and vessels. Latency phase II--1-4 weeks
      with complications caused by inflammatory overlap, contusion pneumonia,
      development of fistulae, internal aspiration. Late phase III--1 month to years-
      special variant of rounded hematoma, pleural inflammation for example in fistulae
      up to scarring fibrosis. Inflammatory complications and development of ARDS with
      subsequent complications in the traumatically pre-damaged pulmonary organ.

PMID- 11824319
TI  - [How can the effectiveness of multimodality therapy concepts be evaluated? From
      the viewpoint of the pathologist].
AB  - Prognostically relevant histopathological grading of tumor regression (grades I
      III) is possible, although laborious. Morphological changes after chemotherapy
      indicate a specific response to treatment with central fibrosis and residual
      tumor islands in the periphery. Prognostic factors, such as TNM categories, UICC
      R status, tumor size, and lymphangiosis, which are not intrinsic part of
      regression grading still correlate with patient survival.

PMID- 11824320
TI  - [Lung contusion--an indication for resection?].
AB  - Pulmonary contusion is the most common injury in blunt chest trauma. Parenchymal
      injury and systemic inflammatory response lead to respiratory insufficiency and
      secondary pneumonia. Early detection and intervention to minimize progression of
      lung consolidation with a low threshold for mechanical ventilation optimize
      treatment results. Between 1990 and 2000 55 thoracotomies or thoracoscopies for
      chest trauma were performed. In 26 patients pulmonary contusion with hematothorax
      (n = 13), endobronchial bleeding (n = 9), bronchopleural fistula (n = 6),
      bronchusruptur (n = 2) or other contusion related injuries (n = 6) was
      responsible for the thoracotomies. We performed 12 lobectomies, 1 pneumonectomy,
      11 parenchymal suture and 2 decortications. Preoperatively a bronchoscopy for the
      localisation of the bleeding and disclosure of central airway injury is
      mandatory. The benefit of bronchoscopy guided blocking of the bronchus for
      endobronchial bleeding is unclear. Video assisted procedures are not useful for
      massive bleeding or anatomical resections.

PMID- 11824322
TI  - [Malignant lung tumors--histomorphological classification, immunohistological
      techniques and prognostic factors].
AB  - Histological typing of lung tumors is based on the new WHO-IASLC classification
      of lung and pleural tumors published in 1999. Based on histological growth
      pattern, the major light microscopic categories of lung carcinomas are squamous
      cell carcinoma, small cell carcinoma, adenocarcinoma and large cell carcinoma.
      The further subclassification within the main categories resembles the high
      degree of lung tumor heterogeneity. Immunohistochemistry may detect
      differentiation that cannot be seen by routine light microscopy on small
      bioptically obtained specimens. Evaluation of the proliferation index of tumor
      cells, hormonal receptors, oncogenes and tumor-suppressor genes is possible.
      Oncogenes, tumor-suppressor genes, angiogenetical factors as well as single cell
      dissemination of tumor cells in lymph nodes are discussed as possible prognostic
      factors.

PMID- 11824321
TI  - [Preoperative administration of new GPIIb/IIIa inhibitors].
AB  - The influence of preoperative abciximab treatment on perioperative risks was
      analyzed. Six groups were formed in consecutive patients (n = 957, 1/1994-3/2000)
      operated upon for CABG according to the urgency of the intervention and the type
      of preoperative haemostaseological treatment. Thirty-one patients underwent
      urgent/emergency CABG with preceding abciximab treatment. After pretreatment with
      abciximab the surgical results did not differ from patients with other types of
      preoperative haemostaseological treatment. CABG can be performed with similar
      results in abciximab pretreated patients as in patients with other types of
      preoperative haemostaseological treatment.

PMID- 11824323
TI  - [Multimodality therapy concept in stage I-IIIA small cell bronchial carcinoma.
      Case follow-up over 15 years].
AB  - We analysed our results of multimodal therapy including chemotherapy,
      radiotherapy and surgery in 150 consecutive patients with SCLC stage I-IIIa
      operated on in our hospital between 1983 and 2000. Median age: 58 years, stages
      see Table 2. Patients with proven SCLC had induction chemotherapy prior to
      surgery. All patients received three cycles of adjuvant chemotherapy, some with
      additional radiotherapy. Perioperative mortality: 2%. Median survival: 22.4
      months. R0 resection was possible in 84% of all patients. Pre- and post-surgery
      staging differed in the majority of the patients. Rotes of 1-, 2- and 5-year
      survival were 79%, 47%, and 32%, respectively. A median survival of 22.4 months
      in multimodally treated LD-SCLC, most of them stage IIb/IIIa appears promising.
      Randomized studies based on clinical staging procedures are not recommended.
      Survival data are promising.

PMID- 11824324
TI  - [Neoadjuvant chemotherapy and chemoradiotherapy in surgically treated non-small
      cell stage III bronchial carcinoma].
AB  - Patients with unfavorable stages of lung cancer are rarely cured with local
      treatment modalities alone. Aim of our phase II trial was to investigate the
      effectivity of a multimodality treatment. Ninety-four patients with NSCLC (stage
      IIIA/IIIB) were treated preoperatively with chemoradiotherapy (cisplatin and
      etoposide, 45 Gy hyperfractionated accelerated radiotherapy). After repeat
      mediastinoscopy patients underwent surgery. Complete resection (R0) was achieved
      in 53% of all patients with NSCLC. Two patients died of sepsis preoperatively and
      four postoperatively (90-days lethality: 6.4%). The median survival time was 20
      months for IIIA and 18 months for IIIB. Calculated survival rates at 6 years were
      34% for IIIA and 17% for IIIB. This multimodality treatment demonstrates high
      efficacy in prognostically unfavorable NSCLC compared with historical controls.

PMID- 11824325
TI  - [Non-small-cell bronchial carcinoma with pathological N2 involvement: adjuvant
      radiotherapy versus adjuvant chemo-radiotherapy].
AB  - Fifty-eight patients, 28 of them included in a German multicenter study, were
      treated either with radiotherapy (5 x 2 Gy/50 Gy) or combined radio-chemotherapy
      (cisplatin 75 mg/m2 d1 in cases with pneumonectomy etoposide 120 mg/m2 d1-3) and
      Ifosfamid 1.5 mg/m2 d1-4, 3 cycles) following surgery in pN2-NSCLC. Metastatic
      disease or local failure was seen in 24 patients (43%), in the majority with
      distant metastasis (n = 21), in 4 patients combined local and distant failure.
      Time to progression (TTP) was 27 to 1172 days, median 244 days. Median survival
      of the whole group was 873 days (= 29 months), the 3-year survival 49%. Comparing
      the two groups there was an advantage (not significant) in favor of the combined
      treated group with a median survival of 1449 days versus 765 days (p = 0.22).

PMID- 11824326
TI  - [Is minimally invasive technique suitable for surgery of lung metastases?].
AB  - Video-assisted thoracic surgery (VATS) for surgery of pulmonary metastases has to
      be defined with respect to technical as well as oncological aspects. Peripheral
      lesions up to 2 cm in diameter can easily be removed by wedge resection, but
      anatomical resection can also be safely accomplished. Since VATS does not allow
      for digital palpation of lung parenchyma, complete resection of all lesions can
      never be guaranteed. Thus, VATS is recommended only for diagnostic and palliative
      procedures but not for curative intention except in randomised studies.

PMID- 11824327
TI  - [New developments in immunosuppressive therapy].
AB  - A highly effective immunosuppressive therapy with as few side effects as possible
      can only be achieved by a reliable drug monitoring. For neoral monitoring of the
      C2 level is essential while for tacrolimus measuring of the trough level is
      sufficient. Due to the different immunogenicity of the organ transplants the type
      and intensity of the immunosuppressive therapy should be organ-specific.
      Sirolimus is highly effective in combination with calcineurin antagonists in
      immunologically high-risk patients. In addition in case of severe side effects
      sirolimus can substitute for the calcineurin antagonists. Il-2 receptor
      antibodies are characterized by minimal side effects and have been shown to be a
      highly effective new therapeutic principle for immunosuppressive induction
      therapy.

PMID- 11824328
TI  - [Prevention and therapy of hemostatic disorders in massive transfusion].
AB  - Adequate periop. analysis of hemostasis taking into account also disorders of
      primary hemostasis considerably contributes to prevention, early detection and
      appropriate treatment of hemostatic disturbances. Standard transfusion protocols
      are advisable in massive transfusion with respect to logistic problems. We
      describe an effective standard protocol based on the initial administration of
      blood components (red cells, plasma, platelets) in a certain fixed ratio which
      then is adapted according to the laboratory test results and the clinical
      situation of the patient. In addition, as soon as the hemostasis shows critical
      values, coagulation factor concentrates (prothrombin complex, fibrinogen, seldom
      single coagulation factors) are administered. Furthermore, desmopressin and
      antifibrinolytics can be successfully used in disorders of primary hemostasis,
      and additionally antifibrinolytics in hyperfibrinolysis or unclear diffuse
      bleeding.

PMID- 11824329
TI  - [Early stomach cancer: endoscopic therapy].
AB  - Endoscopic removal of early gastric cancers is limited to low risk situation: T1m
      (= mucosa) L0 V0 G1-2 R0. In 40 patients pretherapeutic staged as low risk
      cancers the complete endoscopic removal of the lesion was performed. In 75% (29
      out of 40) the pathological specimen proved a low risk cancer. In 16% (5 out of
      29) we found recurrency of the tumor (follow up median 2.5 years). These
      neoplasms were also removed. From the 25% highrisk cases (Sm, G3) 11 patients
      were operated on. Only 2 patients had residual tumor. The complication rate of
      the endoscopic procedures was only 10% (4 x bleeding with transfusion of blood
      units, 1 x perforation), no patient died.

PMID- 11824330
TI  - [Gynecologic injuries, management].
AB  - Accidental trauma to the female perineum is relatively rare and occurs most often
      in the 4- to 12-year-old age group. Vulva and vaginal trauma are the result of
      straddle injuries, accidental penetration, intercourse, sexual abuse and motor
      vehicle accidents. Injuries to the genitalia require typical surgical repair and,
      in association with anogenital or urogenital injuries, a multidisciplinary
      approach.

PMID- 11824331
TI  - [Gene therapy--therapeutic option in treatment of chronic wounds?].
AB  - Chronic wounds seem to be a severe problem in terms of its socioeconomical
      meaning due to the fact that the average age of patients suffering from these
      wounds is rising steadily. Therapy of chronic wounds is complicated and often not
      satisfying. Even application of local growth factors according to the latest
      findings in terms of cell and molecular regulatory mechanisms during wound
      healing does not lead to success because of the immediate inactivation of these
      growth factors in the wound fluid of chronic wounds. Knowing these facts one has
      to ask if new developments such as genetic modification of cells participating in
      wound healing may lead to sufficient results in the therapy of chronic wounds.

PMID- 11824332
TI  - [Possibilities and limits of ambulatory surgery: demands and reality in plastic
      surgery].
AB  - With the development of office-based operating rooms and improved office
      anesthesia, the ability to perform more extensive surgery outside the hospital is
      now given. Experience with the tumescent technique for liposuction and
      abdominoplasty has demonstrated that extensive plastic surgery can performed with
      minimal postoperative discomfort. An emergency phone after surgery is necessary,
      and a call on the operating day evening and the initial postoperative day is a
      safe strategy with high patient acceptance for most types of plastic surgery.
      Additionally, the cost savings of office-based plastic surgery makes this surgery
      much cheaper for the patients and the health insurance organizations.

PMID- 11824333
TI  - [Possibilities and limits of ambulatory surgery--demands and reality in hand
      surgery].
AB  - There are many procedures in hand surgery that from the point of view of a
      hospital staff member do not seem possible or practical to perform in an out
      patient setting, yet can nevertheless safely be done in that fashion. The
      personal situation in regard to the necessary training and up to date knowledge,
      as well as resources in man power and technical equipment require realistic
      assessment to be able to determine the limits in which ambulatory surgery can be
      conducted safely. The hardest factor to calculate always remains the patient, who
      in an out-patient setting easily can evade the necessary control by the surgeon.
      Therefore, it is of surmount importance to achieve a mutual understanding between
      patient and physician. This must be based on comprehensive counselling regarding
      the problem and the surgical procedure including not only all risks and possible
      complications, but also emphasising postoperative measures. Only by achieving
      such a relation can ambulatory hand surgery be performed safely, with efficacy,
      and--above all--with low complication rates.

PMID- 11824334
TI  - [Possibilities and limits of ambulatory operations in vascular surgery: demands
      and reality].
AB  - The requirements for day-case a-v fistula surgery are an effective out-patient
      clinic, adequate surgical and anaesthesiological equipment and a thorough patient
      selection for the planned operation. For surgical reasons, only 87 cases (8.1%)
      out of the 1068 a-v fistula operations carried out had to be admitted to a ward.
      Nevertheless 35% of the patients were on a ward at the time of the operation for
      medical reasons. In case of an ideal co laboration between nephrologists and
      surgeons there should not be more than 10-25% of the dialysis patients in
      hospital at the time of a-v fistula surgery depending on the severity of their
      disease and the planned operation.

PMID- 11824335
TI  - [Chronic anal fissure, therapy].
AB  - According to our experience, fissurectomy is the method of choice in treating
      chronic anal fissure. The secondary lesions and the cicatricial distortions are
      removed. Sphincterotomy is not carried out. We treated 534 patients. Of these,
      470 patients underwent surgery. In 3.1% of those patients in whom the surgical
      scars had healed, fecal spotting occurred postoperatively. There were no further
      continence disorders. The overall result must be regarded as good compared to
      reports in the literature.

PMID- 11824336
TI  - [Experiences with liposuction of established surgeons].
AB  - Liposuction under tumescent local anesthesia is an suitable surgical treatment
      for ambulatory surgical practice.

PMID- 11824337
TI  - [Hernia repair--which technique? Help in making the decision].
AB  - Operation of the inguinal hernia is the most common operation in general surgery.
      Many criteria influence the kind of operation the surgeon will perform. Detailed
      anatomic knowledge of the inguinal region, standardised tactical and technical
      performance of the operation team, careful preparation and a minimum of blood
      loss reduce complications to low levels. These items are the same for all
      operation methods. The Shouldice procedure has been the golden standard for many
      years, nowadays (1998) in America in more than 80% of operations a mesh is
      implanted in the abdominal wall. A Cochran review of EBM showed advantages for
      mesh repair compared to nonmesh repair. Patient oriented decision making in
      choosing a method for inguinal hernia repair should be the new standard of modern
      general surgery.

PMID- 11824339
TI  - [Laparoscopic appendectomy in a general hospital].
AB  - Appendectomy is one of the most commonly performed surgical procedures in general
      surgery. Minimally invasive operative procedures are now generally accepted first
      choice treatments for certain indications (bile stone disease, reflux disease).
      At the present time only about 20% of appendectomies are started laparoscopically
      in Germany. The results of our 255 open appendectomies and 131 laparoscopic
      approaches are summarized. After the minimally invasive procedure we can describe
      a significantly lower incidence of wound infections, a shorter operating time,
      better intraoperative differential diagnostic possibilities and a shorter
      postoperative time of hospitalisation. Therefore, laparoscopic appendectomy is
      the method of choice.

PMID- 11824338
TI  - [Pitfalls in liposuction].
AB  - Liposuction is an easy to learn technique that suits as an outpatient procedure.
      Tight budgets have led to a widespread and sometimes uncritical use. The possible
      mistakes and dangers in patient selection, informed consent, pre- and post-OP
      management are discussed. Other points are the monitoring and the proper use of
      compression bandages.

PMID- 11824340
TI  - [Surgically relevant comorbidity: ability to cooperate].
AB  - The ability to cooperate represents an important prognostic factor for the result
      of any surgical therapy. Cooperation relies on a trustful relationship between
      physician and patient and requires active participation of the patient. Surgical
      procedures requiring long-term follow-up depend on a high degree of cooperation.
      Cooperation is the result of numerous psycho-social factors. The degree of
      potential cooperation influences to a large extent the decision process for
      indication and choice of method. The ability to cooperate does not depend on the
      patient only but it is result of a therapeutic alliance between patient and
      physician.

PMID- 11824341
TI  - [Surgically relevant comorbidity: lung function].
AB  - The risk of surgical procedures is strongly affected by coexisting pulmonary
      disease. Patient related risk factors for pulmonary disorders in the
      perioperative period are poor medical condition, old age, obesity, smoking, COPD,
      and bronchial asthma. Thoracic surgery and upper abdominal surgery are the most
      important procedure related risk factors for pulmonary complications in the
      perioperative period. Preoperative evaluation of lung function, assessment of the
      perioperative pulmonary risk, identification of high risk patients, and
      preoperative improvement of lung function, if possible, result in an improved
      outcome of surgical procedures due to a reduction of perioperative pulmonary
      complications.

PMID- 11824342
TI  - [What might be the role of the German Society of Surgery in introducing a new
      method?].

PMID- 11824343
TI  - [Visceral surgery from the viewpoint of the German Society of Visceral Surgery
      and the German Society of Surgery].

PMID- 11824344
TI  - Robotic assistance: current available method and its evolution in visceral
      surgery.

PMID- 11824345
TI  - [Forensic aspects of a trainee in robotic surgery of the heart].
AB  - The grounds for liability with robotic surgery include damage to patients,
      causality, illegality and guilt. The patient must receive very comprehensive
      information on the treatment under consideration, his/her risk and what will be
      done in the case of technical failure. The surgeon operating the robotic device
      is obliged to provide normal conscientious care and state-of-the-art treatment.
      In addition, there is possible neglect of supervisory duties vis-a-vis other
      hospital personnel to be considered. A special problem is posed by a forensic
      physician who lacks experience in robotic surgery. There should be a surgeon at
      the operating table who is at least equally skilled as the surgeon operating the
      monitor. Robotic surgery must ultimately be at least as effective as conventional
      surgery, if not better. It must, however, be borne in mind that in cases
      involving this new technology, it is that patient who is the pioneer.

PMID- 11824346
TI  - [Dissection technique--is ultrasound the best method?].
AB  - Preventive hemostasis is extremely important in endoscopic surgery. Ultrasonic
      dissectors are used very often. We tested the occlusion safety of bipolar forceps
      and ultrasonic dissector for porcine vessels. Thermographic videos showed maximum
      temperature up to 200 degrees C when using one ultrasonic dissector. The lateral
      damage zone in vivo and in vitro measured between 2 and 6 mm.

PMID- 11824347
TI  - [Technical standards in surgical procedures].
AB  - Laparoscopic cholecystectomy is the "gold standard" for treatment of symptomatic
      cholelithiasis. Trocar placement and position of the operating team depend from
      the chosen patient positioning (French/American). After testing the technical
      equipment, the pneumoperitoneum is established, a 10 mm camera trocar is inserted
      in the umbilicus, the peritoneal cavity is explored, tension to Calot's triangle
      is applied, blunt dissection of d. cyst and a. cyst with exposition of the common
      bile duct, clipping, selective use of cholangiography, retrograde removal of the
      gallbladder.

PMID- 11824348
TI  - [Current patient education problems for the physician].
AB  - Every medical treatment which involves risk to the patient requires the informed
      consent of the patient. Taking into account the fundamental right of the patient
      to remain physically unscathed and the right of self-determination, proper
      information must be given to the patient regarding typical risks. This is a
      prerequisite to patient consent. In this regard, the law makes strong demands.
      Even in cases where medical treatment is unsuccessful due to complications beyond
      the physician's control, the physician is still held liable (even if there was no
      fault found in his medical treatment) if he had not properly informed his patient
      of the risk involved in the procedure or he cannot prove that he had informed the
      patient. The following paper explains the legal demands of the duty to inform
      patients along with examples of precedents.

PMID- 11824349
TI  - [Requirements for documentation by the physician].
AB  - Medical documentation, which is required by law, serves various purposes: for
      therapy, to provide information to other physicians who are or may be involved;
      as a record if there is any disagreement with a patient; and for invoicing
      purposes. Depending on which of these aspects is being addressed, the
      documentation is expected to satisfy different demands. With regard to liability,
      any information pertaining to the patient's medical condition should be recorded
      as soon as possible in correspondence to the principles of truth and clarity. For
      the health insurance companies, all treatments and services rendered must be
      submitted in writing. The power of proof of medical documentation is understood
      differently from the point of view of liability and health insurance law.

PMID- 11824350
TI  - [Conclusions and consequences from registries: the Polytrauma Register of the
      German Society of Trauma Surgery].
AB  - In the trauma register of the German society of traumatology until now 5353
      patients have been analysed. The mean age was 38.5 years, the proportion of blunt
      injuries was 94.3%. The mean ISS was 24.8%, the emergency doctor arrived in the
      middle 22.4 minutes after the accident. The stay of the emergency doctor lasted
      32.9 minutes and the transport from the place of accident to the hospital took
      18.3 minutes. The rate of intubation through the emergency doctor was 58.3%. The
      mean stay at hospital was 31.1 days, at the intensive car unit 13.1 days with a
      mean time of 8.7 days artificial respiration. In comparing the years we saw an
      improvement of outcome throughout all participating hospitals. Future aims of the
      trauma register are to increase the quality of life after trauma, to guarantee an
      adequate quality of treatment, to analyse costs and to include all German
      hospitals in the trauma register.

PMID- 11824351
TI  - [How does a lawyer evaluate the introduction of a new treatment method (the so
      called learning curve)].
AB  - In the interest of our patients and advancement in medicine and with the
      guarantee by law of the freedom to select methods of treatment, we may and must
      try out new strategies even in the face of initially unknown risks, side effects,
      and consequences. Every innovation assumes, however, that the advantages and
      disadvantages, potential complications, and burden to the patient have been
      weighed against those of conventional methods. The risks that a pioneer takes
      must be justified and presented comprehensively and clearly to the patient.
      Otherwise the threat is posed of civil and criminal accusations of negligence in
      responsibility or in the obligation to fully inform patients. Patient protection
      and safety must always be the first priority.

PMID- 11824352
TI  - [The methicillin-resistant Staphylococcus aureus problem: public health-
      rituals].
AB  - Measures employed to control MRSA infections are frequently not proven
      scientifically and therefore constitute mere rituals. The German-speaking Working
      Group for Hospital Infection Control recommends that surgery on MRSA patients be
      performed in one surgical unit only at the very end of the operation program,
      even if this means postponing surgery to the evening or night hours. From a
      hygiene point of view this is unnecessary. Data presented here describe the most
      common modes and routes of S. aureus transmission during surgery. Other rituals
      during preoperative preparation, washing and disinfecting the hands or procedure
      after so called septic interventions, visiting the lavatory etc. are described.

PMID- 11824353
TI  - [Methicillin-resistant Staphylococcus aureus--the pathogen].
AB  - Methicillin resistant Staphylococcus aureus (MRSA) are resistant to all beta
      lactams, and in more than 90% to ciprofloxacin and in 50-60% also to other groups
      of antibiotics, glycopeptides, quinupristin and linezolid excluded. A special
      problem is posed by glycopeptide intermediate susceptible S. aureus (GISA) which
      are until now rate in Germany, By molecular typing epidemic MRSSA can be
      identified which have a pronounced capacity for intra- and interhospital spread.
      MRSA are not more but also not less virulent than sensitive S. aureus.

PMID- 11824354
TI  - [Diagnosis of pancreas tumors: MRI or multidetector spiral CT?].
AB  - Recent technical advances in the field of abdominal MRI and multi-detector spiral
      CT (MSCT) have resulted in improved diagnostic capabilities of pancreatic tumors.
      Preliminary data demonstrate slight advantages of MRI in the detection of liver
      metastases and papillary tumors as well as in the differential diagnosis of
      pancreatic masses while MSCT might be advantageous in the assessment of vascular
      infiltration, particular in uncooperative patients.

PMID- 11824355
TI  - [Surgical therapy of abdominal infection--reliable strategies].
AB  - The differential treatment of abdominal sepsis is based on surgical eradication
      of the infectious focus, intensive care, and administration of antibiotics. The
      eradication of the focus can be done by interventional or operative procedures.
      Between January 1980 and December 2000, 2214 patients with peritonitis were
      treated in AK Hamburg-Altona. A total of 1520 cases were successfully treated by
      standard therapy; 694 cases needed treatment by staged lavage. The postoperative
      mortality in this group was 17.3%. Objective comparison is difficult because of
      diversity of patient groups and the complexity of chosen surgical therapy.
      Therefore none randomized clinical study does exist up to the present. Indication
      and application of selected therapeutic technique result from clinical criteria
      and experience.

PMID- 11824356
TI  - [DRGs in surgery from the viewpoint of a clinic].
AB  - Because of the significance that documentation has in order for the first DRG
      budget to be drafted in 2003, priority has to be given in all surgical
      departments to assuring that codification is of a very high standard. Clinical
      management and senior surgeons will have to develop strategies which enable them
      to maintain patient care, a range of services, and efficiency in their surgical
      departments. Defining and concentrating on core competences and the value chain
      in surgery will be of increasing importance in their ability to assert themselves
      in future. The introduction of the DRG system will give new value to the
      surgeon's role in modern departments and in clinical management.

PMID- 11824357
TI  - [Quality assurance--quo vadis? What expectations does science have? From quality
      assurance to health services research].
AB  - Surgical quality control may be developed in applied research. Using methods of
      clinical epidemiology, the efficacy of therapeutic and diagnostic procedures may
      be tested in wide fields of patient care. Thereby deficits may be unvealed very
      rapidly. Applied research pointing towards patient care has to be
      interdisciplinary and multicentric. A specific role has to be taken by the local
      boards of medicine.

PMID- 11824358
TI  - [Thoracic surgery centers].
AB  - The term "center for thoracic surgery" needs to be defined with respect to
      "thoracic surgery" and "center". "Thoracic surgery" includes the knowledge, the
      technical skills, and the experience, which allows for a correct diagnosis and
      the surgical treatment of diseases of the chest (chest wall, pleura, lungs,
      trachea, bronchi, mediastinum, diaphragm and adjacent structures). The "center"
      is defined by the specific organisational structure facilitating
      interdisciplinary patients care according to international standards, education
      and training of surgeons and continuous clinical and experimental investigation
      in the field of thoracic surgery.

PMID- 11824359
TI  - [Concepts of the German Society of Tropical Surgery].
AB  - The DTC promotes access to surgical care facilities of acceptable medical quality
      for all people in third world countries. To achieve this goal following concepts
      and activities are persued: Establishment of a 2-year training programme district
      surgery Postgraduate surgical training in Germany Workshops and annual scientific
      meetings Development of adapted surgical technologies Cooperation with national
      and international organisations Promotion of north-south partnerships between
      colleagues and hospitals.

PMID- 11824360
TI  - [Surgical spectrum in peace-keeping missions].
AB  - Peace-keeping "out of area missions" of the Federal German Armed Forces are
      supported by modular container hospitals. The infrastructure of mobile container
      hospitals reflects the modern standard of surgery in "out of area" missions. The
      injury pattern of over 200 patients with war injuries, caused by AK 47
      Kalaschnikov, fragments and mines are presented.

PMID- 11824361
TI  - [Surgery and molecular biology: new insight or stray path?].
AB  - Surgery has the optimal possibility for theoretical-clinical transfer of
      molecular biological knowledge. On the basis of the existing research emphasis on
      clinical molecular biology at the Department of Surgery, University of
      Heidelberg, this is shown by the example of colorectal cancer: Establishment of a
      large clinical register for hereditary colorect cancer, use of molecular
      biological methods to improve phenotype/genotype correlations, definition of risk
      groups, decision on surgical therapeutical concepts for hereditary cancers and
      considerations on the creation of problem-orientated centers for hereditary
      cancer. A further example for the application of molecular methods is the
      detection of minimal residual disease or tumor cells in the different
      compartments (blood, lymph nodes, bone marrow and peritoneum) in order to achieve
      a better risk evaluation exceeding the standard pathohistological stage
      definition. The goal is an individualized or more focused therapy for each
      patient. Transfer of research from the basic sciences into the clinical setting,
      integrated into the daily clinical work, is possible in a so-called tandem model.

PMID- 11824362
TI  - [Reality in carrying out clinical studies in a non-university hospital].
AB  - Carrying out clinical research at non-university hospitals is complicated by a
      lack of appropriate material and staffing resources, but is necessary considering
      the far greater number of patients attending (approximately 80%). A poll of
      surgical department heads (n = 27) revealed that, nevertheless, scientific
      research, was carried out by a majority of them. Retrospective studies and case
      studies are being carried out in the majority at single centers, whereas for
      multicenter studies participation in prospective randomized studies predominates.
      Preferred subjects are surgical strategies and techniques. Publications are
      primarily in German, most of them being original articles. It is striking that
      there is a relatively high percentage of abstracts amongst the publications in
      English. Improved know-how and coordination centers simplify, while lack of time,
      increasingly similar performance figures, and wildly growing documentation
      complicate studies.

PMID- 11824363
TI  - [Perianal precancerous conditions (Bowen disease, Paget disease, Carcinoma in
      situ, Buschke-Lowenstein tumor)].
AB  - Perianal premalignant lesions are rare. Any suspicious perianal lesion or any
      perianal exanthema, that does not heal by non-surgical treatment has to be
      biopsied for histology. Many premalignant lesions are diagnosed as an incidental
      finding after anorectal surgery: any anorectal specimen must be examined by the
      pathologist. Leukoplakia is a facultative premalignant condition. High-grade anal
      intraepithelial neoplasia (AIN) is an in situ squamous cell carcinoma, associated
      with papillomavirus infection. Bowen's disease and Bowenoid papulosis are
      clinical variations of high-grade AIN. Buschke-Lowenstein tumour (giant
      condyloma) is a locally destructive tumour, that does not infiltrate or cause
      metastases. Paget's disease is a premalignant lesion like AIN, associated with
      other malignancies.

PMID- 11824364
TI  - [Preventive and pre-emptive concepts in the acute hospital].
AB  - This study aimed at developing an efficient pain therapy with preventive
      conceptions for the clinical routine. Since 30-75% of all patients suffer from
      unbearably strong pain. Before establishing an efficient treatment, 100 patients
      were asked about efficiency of pain treatment. After establishing the actual
      state of matters, all medical collaborators and nursing personnel were trained an
      improved pain management. Afterwards, another 100 patients were questioned for
      comparison. The results showed significant improvements in the reduction of pain
      intensity and frequency. Higher satisfaction and efficiency of pain treatment
      were documented as well as the reduction of accompanying vegetative symptoms.

PMID- 11824365
TI  - [Clinical research in a university hospital--how we do it in Austria].
AB  - Evaluation of quality of work in surgical society is based in clinical and
      scientific output. Scientific quality of the publications is calculated on the
      basis of impact factors of journal ranking. Clinical evaluation is based on
      catalogues of operations performed and voluntary examination in a special
      surgical field. Total scientific output increased in Austria during the last
      decade achieving higher level as compared to Germany but lower than in
      Switzerland. Scientific and clinical standards in a teaching institutions should
      be kept high allowing candidates to succeed in competition for top positions.

PMID- 11824366
TI  - [Coordination centers for clinical studies--structure and integration of non
      university hospitals].
AB  - The Integration of non-university hospitals in clinical trials is absolutely
      necessary to ensure patient availability and generalisation. In our survey we
      observed significant problems with the conduction of clinical trials in non
      university hospitals. Important aspects of these problems are caused by the lack
      of infrastructure and personnel as well as by rising standards for clinical
      conduction. The establishment of Coordination Centres for Clinical Trials (KKS)
      has significantly improved the ability to support clinical trials in non
      university hospitals in the future.

PMID- 11824367
TI  - [Integrating non-university institutions into clinical research. The example of
      implementing the concept of quality of life into regional management of cancer
      patients].
AB  - Implementation is the stepwise introduction of a concept with the goal to change
      the behaviour of health care providers. The concept of quality of life (QL) was
      implemented in order to improve the regional care for cancer patients. The
      following steps were taken: creating a quality circle, teaching the concept QL,
      listing QL-enhancing therapy options, graphically presenting individual patients
      in the form of QL-profiles. In the course of an implementation study QL-profiles
      of individual patients were sent to their respective practitioners. Doctors
      judged these profiles as comprehensible (100%) and informative (55%). QL-profiles
      influenced doctor-patient communication (42%), but had no impact on therapeutic
      decisions (0%). Acceptance of QL-profiles was higher in doctors treating breast
      cancer patients (67% response rate) than in doctors treating rectal cancer
      patients (25%). Reasons for this difference as well as driving and restraining
      forces for implementing the QL-concept were analysed through a barrier analysis.

PMID- 11824368
TI  - [Can molecular genetic knowledge from studies of hereditary carcinoma be applied
      to sporadic colorectal carcinoma?].
AB  - Colorectal carcinomas without a family history are considered to be "sporadic"
      carcinomas, however, also have a genetic basis. Within the hereditary forms there
      are 15-50% of patients without a family history being carriers of de novo
      germline mutations. In addition, non-pathogenic polymorphisms in these
      tumorsyndrome-genes as well as in genes involved in the carcinogen metabolism
      (GST, NAT, CYP, MTHFR) are associated with an increased or decreased colorectal
      cancer risk. Identification of these genetic risk factors will enable
      individually tailored surveillance and recommendations for prophylaxis as well as
      individually tailored treatment.

PMID- 11824369
TI  - [Gene therapy in diabetic foot].
AB  - In gene therapy nucleic acids are used for therapy. There are three different
      concepts in gene therapy for chronic wounds. (1) Synthesis of human recombinant
      growth factors by gene therapy techniques, (2) Ex-vivo transfection of cell
      cultures (fibroblasts, keratinocytes) with growth factor DNA and subsequent
      transplantation of transfected cells on chronic wounds. (3) In-vivo transfection
      with growth factor DNA, e.g., gene gun, liposomes, viral vector. Clinical studies
      on gene therapy for diabetic foot ulcers are only available for the local
      application of human recombinant PDGF-BB growth factor. Meta-analysis shows there
      is a low but significant effect of PDGF-BB on neuropathic diabetic ulcers,
      leading to an increase of healing by 10-15% within 20 weeks of treatment.

PMID- 11824370
TI  - [Growth factors for preventing amputation in delayed wound healing].
AB  - Growth factors are mediators with essential importance for undisturbed repair
      process after wounding. The coordinated concert of these substances is necessary
      for healing with complete restoration of function and morphology. These complex
      mechanisms are disturbed during secondary and delayed repair. Local and systemic
      application of these growth factors seems to add important instruments for
      therapeutic use in the treatment of chronic wounds. Knowledge from experimental
      research is encouraging, although the exact mechanisms of synergistic action are
      not completely understood. However, the results from clinical use in controlled
      studies do not meet these expectations by far. Leading results from experimental
      and clinical studies are summarized in detail. Further intensive research however
      is required for the rational use of growth factors in the clinical setting.

PMID- 11824371
TI  - [Technique of right laparoscopic hemicolectomy].
AB  - Patho-anatomic feature such as easy mobilisation of the colon segment on
      mesocolon, technically easy approach to the central lymphovascular pedicle, and
      the possibility of relative uncomplicated salvage and anastomosis warrant
      including this method in the procedures of modern colorectal surgery.
      Mobilisation from the vascularisized mesenterial bridges in a window technique,
      transection of the ileocolic lymphovascular pedicle, lateral and proximal
      mobilisation of ileocoecum, colon ascendance, right flexure and proximal
      transversum. After enlargement of one trocar incision the exteriorized colon is
      resected and an extracorporeal anastomosis is performed in the standard manner.
      With this standardized method, right hemicolectomy is easy, practicable, and
      repeatable and can be done with all the advantages of minimally invasive surgery.

PMID- 11824372
TI  - [Progress in oncological visceral surgery: colon carcinoma].
AB  - The main progress in surgical oncology regarding colonic cancer has been made by
      standardizing the mode of resection: En block resection of the tumor-bearing
      colon segment together with the draining lymph nodes, including the lymph nodes
      at the origin of the respective main vessel, is mandatory. Minimal invasive
      surgery is an option for resection, however, results of ongoing multicenter
      trials have to clarify the situation. Adjuvant therapy is used for patients in
      stage III, who are not included in studies. Since quality of surgery has a major
      influence on prognosis, this factor also needs to be taken into account when
      judging the impact of adjuvant therapy. New chemotherapeutic agents have been
      proven to be valid for palliative and probably also for adjuvant treatment.
      Prophylactic surgery is routine for patients with ulcerative colitis and FAP, the
      benefit for patients with HNPCC has to be further evaluated. New knowledge on the
      individual prognosis might optimize treatment; most probably this will be
      accomplished by detection of minimal residual disease. The impact of the sentinel
      node concept in colon cancer is unclear. New progress will be possible by an
      approach adapted to the individual problem together with accumulating and linking
      experience and knowledge.

PMID- 11824373
TI  - TGF beta is required for the formation of capillary-like structures in three
      dimensional cocultures of 10T1/2 and endothelial cells.
AB  - New vessels form de novo (vasculogenesis) or from pre-existing vessels
      (angiogenesis) in a process that involves the interaction of endothelial cells
      (EC) and pericytes/smooth muscle cells (SMC). One basic component of this
      interaction is the endothelial-induced recruitment, proliferation and subsequent
      differentiation of pericytes and SMC. We have previously demonstrated that TGF
      beta induces the differentiation of C3H/10T1/2 (10T1/2) mesenchymal cells toward
      a SMC/pericyte lineage. The current study tests the hypothesis that TGF beta not
      only induces SMC differentiation but stabilizes capillary-like structures in a
      three-dimensional (3D) model of in vitro angiogenesis. 10T1/2 and EC in Matrigel
      were used to establish cocultures that form cord structures that are reminiscent
      of new capillaries in vivo. Cord formation is initiated within 2-3 h after
      plating and continues through 18 h after plating. In longer cocultures the cord
      structures disassemble and form aggregates. 10T1/2 expression of proteins
      associated with the SMC/pericyte lineage, such as smooth muscle alpha-actin (SMA)
      and NG2 proteoglycan, are upregulated in these 3D cocultures. Application of
      neutralizing reagents specific for TGF beta blocks cord formation and inhibits
      expression of SMA and NG2 in the 10T1/2 cells. We conclude that TGF beta mediates
      10T1/2 differentiation to SMC/pericytes in the 3D cocultures and that association
      with differentiated mural cells is required for formation of capillary-like
      structures in Matrigel.

PMID- 11824374
TI  - Mg(++)-induced endothelial cell migration: substratum selectivity and receptor
      involvement.
AB  - The activation of endothelial cells during angiogenesis requires cell spreading
      and migration. These processes are influenced by extracellular signals such as
      chemoattractants from the local microenvironment. We have shown previously that
      transmembrane Ca++ influx is necessary for motility and cell spreading, thus we
      hypothesized that the extracellular divalent cations Mg++ and Ca++ may regulate
      human umbilical vein endothelial cell (HUVEC) spreading and act as
      chemoattractants. Studies demonstrated that extracellular Mg++ induced a
      statistically better spread phenotype when cells were plated on multiple
      extracellular matrix substrata; Ca++ promoted cell spreading only on vitronectin.
      Mg++ but not Ca++ acted as a potent chemoattractant when HUVEC migrated on
      gelatin- and type IV collagen- but not on vitronectin-coated filters. A
      checkerboard analysis of migration showed that Mg++ induces both chemokinetic and
      chemotactic migration peaking at 0.1 and 10 mM, respectively. An equivalent
      effect of oligomycin was seen on motility to Mg++ or to vascular endothelial
      growth factor (VEGF) in extracellular Mg(++)-free conditions, ruling out an
      exclusive role for Mg++ as a migration energy producer. The Mg(++)-stimulated
      chemotaxis was inhibited > 60% by pertussis toxin, d-erythrosphingosine, and
      tyrphostin B48, but unaffected by cholera toxin exposure. These data suggest that
      Mg(++)-induced chemotaxis may be promoted through a Gi protein-coupled receptor
      pathway with a requirement for protein kinase C activity and protein tyrosine
      phosphorylation. Thus, Mg++ may be a newly recognized receptor-mediated
      chemoattractant for endothelial cells.

PMID- 11824375
TI  - Production and characterization of a Tie2 agonist monoclonal antibody.
AB  - The Tie2 receptor and its known ligands, the angiopoietins, play a critical role
      in endothelial cell differentiation during the process of angiogenesis. Recent
      experimental observations indicate that the agonistic ligand, angiopoietin-1, can
      stimulate endothelial cell sprouting and act as a chemo-attractant in vitro and
      induce increased and enhanced angiogenesis both alone and in conjunction with
      vascular endothelial growth factor (VEGF) in vivo. Here, we present a monoclonal
      antibody (MAb), which binds to the extracellular portion of the Tie2 receptor and
      elicits similar agonist effects. Upon MAb binding to the native Tie2 receptor of
      cultured human umblical vein endothelial cells (HUVEC), there is a rapid increase
      in receptor autophosphorylation with a concomitant enhancement in the recruitment
      and association of the signalling intermediates Grb2 and SH-PTP2. The antibody
      further demonstrates functional activity in vascular tissues. In vitro, the
      antibody promotes the survival of cultured HUVEC and elicits a dose dependent
      outgrowth and branching of microvessels from cultured explants of rat aorta. When
      administered in vivo, the antibody enhances the vascularization of subcutaneous
      Matrigel implants in mice. Together these data suggest that the antibody is
      capable of acting as a surrogate ligand for Tie2 and further confirms the role of
      Tie2 in the differentiation of endothelial cells during angiogenesis.

PMID- 11824376
TI  - An ex vivo angiogenesis assay utilizing commercial porcine carotid artery:
      modification of the rat aortic ring assay.
AB  - The study of angiogenesis as a therapeutic target requires a reliable,
      physiologically relevant, and technically straightforward assay. An ex vivo assay
      bridges the gap between cell-based assays, which may not realistically represent
      the complex process of vessel sprouting, and in vivo assays, which are time
      consuming and expensive. Porcine carotid arteries provide an ideal tissue source
      for angiogenesis inhibitor screens due to their availability, physiological
      relevance and large size. 1.5 mm2 fragments of porcine carotid arteries were
      incubated in 48-well culture plates and sandwiched between two 100 microliters
      layers of Matrigel. Sprouting was observed from the explants and quantitated,
      using a digital imaging system, after two weeks of incubation. Histological
      analysis using Factor VIII-related antigen (von Willebrand Factor) as an
      endothelial cell-specific marker identified these sprouts, which were consistent
      with endothelial cell morphology, supporting the system as a model of
      angiogenesis. Accordingly, the angiogenesis inhibitors suramin, 2
      methoxyestradiol, and the matrix metalloprotease inhibitor Batimastat were shown
      to completely inhibit sprouting at 50, 0.5, and 5.0 micrograms/ml, respectively
      and to have ED50 values of 23, 0.15, and 0.14 microgram/ml. This assay shows good
      reproducibility and eliminates animal to animal variation. The system should
      prove adaptable to other forms of angiogenic stimulation, ultimately making a
      variety of assays for angiogenesis available to laboratories of limited
      resources.

PMID- 11824377
TI  - Platelets and vascular endothelial growth factor (VEGF): a morphological and
      functional study.
AB  - The growth of primary tumours beyond a critical mass is dependent on
      angiogenesis. The switch to the angiogenic phenotype involves changes in the
      local equilibrium of cytokines with either pro- or anti-angiogenic properties.
      Vascular Endothelial Growth Factor (VEGF) is one of the major positive regulators
      of tumour angiogenesis. Serum VEGF is, in cancer patients, correlated with worse
      prognosis. Recent evidence suggests that platelets are the main contributors of
      serum VEGF. We demonstrate, ultrastructurally and with immunofluorescence
      techniques, the alpha granule and membranous localisation of VEGF and provide
      further evidence for the role of platelets, both in healthy individuals as in
      patients with locally and advanced breast cancer, in the storage of circulating
      VEGF. We also demonstrate that, linear with tumoural progression, platelets
      accumulate more VEGF. Enhanced production in bone marrow platelet progenitors as
      well as endocytosis of circulating VEGF by platelets and/or megakaryocytes could
      explain the higher VEGF load in platelets from advanced cancer patients. This
      study provides further evidence for a role of platelets in transporting VEGF.

PMID- 11824378
TI  - Designed beta-sheet peptides that inhibit proliferation and induce apoptosis in
      endothelial cells.
AB  - Novel beta-sheet-forming peptide 33 mers, beta pep peptides, have been designed
      by using a combination approach employing basic folding principles and
      incorporating short sequences or proposed key residues from the beta-sheet
      domains of interleukin-8 (IL-8), platelet factor-4 (PF4) and
      bactericidal/permeability increasing protein (B/PI). Since PF4 and B/PI are anti
      angiogenic and IL-8 is angiogenic, the library of 30 beta pep peptides was
      assayed for the ability to affect the growth of endothelial cells. Results
      indicate that five beta pep peptides (beta pep-2, 7, 8, 21 and 25) demonstrate
      greater than 50% anti-proliferative activity at 30 micrograms/ml, and one of
      those (beta pep-25) is similarly active at 10 micrograms/ml. Insight into the
      mechanism of action was probed in an apoptosis assay. Anti-proliferative activity
      was found to be correlated with the induction of apoptosis. For example, at 100
      micrograms/ml beta pep-25 induces 85% of endothelial cells to undergo apoptosis
      within 2 days. These effects from beta pep peptides appear to be selective for
      endothelial cell (EC) because normal cells (fibroblasts and leukocytes) and
      various tumor cells are not significantly affected at peptide concentrations used
      in this study. Comparison of active and inactive beta pep sequences allows
      structure-function relationships to be deduced. Five hydrophobic residues and two
      lysines appear to be crucial to activity. This research contributes to the
      development of novel anti-angiogenic peptides.

PMID- 11824379
TI  - Involvement of VEGFR-2 (kdr/flk-1) but not VEGFR-1 (flt-1) in VEGF-A and VEGF-C
      induced tube formation by human microvascular endothelial cells in fibrin
      matrices in vitro.
AB  - Different forms of vascular endothelial growth factor (VEGF) and their cellular
      receptors (VEGFR) are associated with angiogenesis, as demonstrated by the
      lethality of VEGF-A, VEGFR-1 or VEGFR-2 knockout mice. Here we have used an in
      vitro angiogenesis model, consisting of human microvascular endothelial cells
      (hMVEC) cultured on three-dimensional (3D) fibrin matrices to investigate the
      roles of VEGFR-1 and VEGFR-2 in the process of VEGF-A and VEGF-C-induced tube
      formation. Soluble VEGFR-1 completely inhibited the tube formation induced by the
      combination of VEGF-A and TNF alpha (VEGF-A/TNF alpha). This inhibition was not
      observed when tube formation was induced by VEGF-C/TNF alpha or bFGF/TNF alpha.
      Blocking monoclonal antibodies specific for VEGFR-2, but not antibodies
      specifically blocking VEGFR-1, were able to inhibit the VEGF-A/TNF alpha-induced
      as well as the VEGF-C/TNF alpha-induced tube formation in vitro. P1GF-2, which
      interacts only with VEGFR-1, neither induced tube formation in combination with
      TNF alpha, nor inhibited or stimulated by itself the VEGF-A/TNF alpha-induced
      tube formation in vitro. These data indicate that VEGF-A or VEGF-C activation of
      the VEGFR-2, and not of VEGFR-1, is involved in the formation of capillary-like
      tubular structures of hMVEC in 3D fibrin matrices used as a model of repair
      associated or pathological angiogenesis in vitro.

PMID- 11824380
TI  - CM101 stimulates cutaneous wound healing through an anti-angiogenic mechanism.
AB  - CM101, an anti-pathoangiogenic polysaccharide derived from group B streptococcus,
      has been shown to inhibit inflammatory angiogenesis and accelerate wound healing
      in a mouse model and minimize scarring/gliosis following spinal cord injury. To
      evaluate the in vivo effects of CM101 on cutaneous wound healing in the pig,
      intravenously delivered CM101 or placebo vehicle was given 1 h after cutaneous
      wounding and again at 72 h after injury. Tissues from partial-thickness and full
      thickness excisions were collected at days 4 and 7 after wounding and evaluated
      for a variety of standard healing parameters. Both types of CM101-treated wounds
      showed significantly less evidence of inflammatory angiogenesis when assessed by
      macroscopic photography of the wound surface, qualitative histological
      observations, laser doppler perfusion imaging, and quantitative morphometric
      analysis of microvessel area from endothelium selectively immunostained for
      factor VIII. Resurfacing was accelerated in partial-thickness and full-thickness
      excisions that received two doses of CM101 as compared to the placebo-treated
      excisional wounds. Neodermal thickness was increased in CM101-treated wounds at
      day 4 and was slightly reduced in comparison with placebo by day 7. New collagen
      accumulation appeared to be unaffected by the CM101 treatment.
      Immunohistochemical staining using a polyclonal antisera directed against the
      anti-pathoangiogenic CM101 target protein HP59 on day 7 indicated a strong
      immunoreactivity on the microvessels present in the control wounds but not in
      wounds of the CM101-treated animals. In summary, the immunolocalization HP59 in
      the microvessels of the cutaneous wound bed in control but not in CM101 treated
      wounds suggests that CM101 inhibits the pathologic inflammatory angiogenesis
      accompanying the normal granulation processes. The net biological effect of
      inhibited inflammatory pathoangiogenesis is a diminished, suggested and purely
      physiologic, microvascular bed which translates into an enhanced rate of
      epithelial resurfacing and therefore an overall accelerated rate of wound repair.

PMID- 11824381
TI  - A study of metabolites as intermediate effectors in angiogenesis.
AB  - Metabolites released from hypoxic tissues have been reported as angiogenic
      factors in circumstances of reduced tissue oxygenation or an increased rate of
      metabolism. However, in more recent reports their possible role in angiogenesis
      prior to the induction of hypoxia-inducible genes appears to have been neglected.
      In a systematic attempt to evalaute their role, metabolites common to the
      glycolytic and oxidative pathways (nicotinamide adenine dinucleotide, adenosine
      diphosphate and adenosine triphosphate), exclusively glycolytic metabolites
      (pyruvate and lactic acid) and exclusively oxidative metabolites (malate,
      succinate, fumarate and citrate) were tested to assess their effects upon in vivo
      angiogenesis and in vitro endothelial cell migration and proliferation. In
      addition, adenosine was tested due to its proposed role in hypoxia-induced
      angiogenesis. The angiogenic effects in vivo were examined using the chick
      chorioallantoic membrane assay and in vitro on chick embryonic capillary
      endothelial cells using a phagokinetic track/migration assay and crystal violet
      dye binding/proliferation assay. Metabolites common to the glycolytic and
      oxidative metabolic pathways and exclusively glycolytic metabolites produced an
      angiogenic response in vivo and in vitro on endothelial cell proliferation and
      migration, whereas exclusively oxidative metabolites, with the exception of
      malate, did not. Adenosine caused an increased proliferation of blood vessels in
      vivo and stimulated endothelial cell migration and proliferation. Overall, these
      results implicate metabolites as effectors in angiogenesis and it is proposed
      that they have a role which is possibly independent of the upregulation of
      hypoxia-inducible genes.

PMID- 11824382
TI  - Feto-maternal interface of human placenta inhibits angiogenesis in the chick
      chorioallantoic membrane (CAM) assay.
AB  - The rapidly growing chorionic villi of the human placenta characteristically show
      constant blood vessel growth and differentiation. In contrast, the underlying
      decidua reveals tissue remodeling without apparent angiogenesis. Using the chick
      chorioallantoic membrane (CAM) assay, we found marked inhibition of angiogenesis
      by the feto-maternal interface tissue derived from nine human placentas obtained
      minutes after delivery. Inhibition was prevented by the addition of monensin,
      which blocks the release of synthesized cell products, and was markedly reduced
      by drying or freezing the tissue before the assay. Histology, combined with
      statistical analysis of the constituent cell types, correlated inhibition of
      angiogenesis with the number of fetally-derived extravillous trophoblasts in the
      feto-maternal interface tissue. Electron microscopy revealed endothelial cell
      damage in preexisting small (but not large) CAM vessels. We conclude that
      decidual tissue inhibited angiogenesis by releasing a water soluble factor which
      was under apparent constant production by vaible trophoblast on the CAM. The
      extravillous trophoblast population resembles tumor cells in its migratory and
      invasive properties but, in contrast to tumor induced angiogenesis, it is
      angiostatic, perhaps to counteract angiogenic proteins leaking from the
      intervillous space which could be detrimental to the maternal organism if active.

PMID- 11824383
TI  - [Significance of expanded polytetrafluoroethylene chin prosthesis in profile
      plastic surgery].

PMID- 11824384
TI  - Dental access centres.

PMID- 11824386
TI  - Comment on: Fujii T, Hasegawa RT, Sitoh Y et al. Chromoscopy during colonoscopy.
      Endoscopy 2001; 33:1036-1041.

PMID- 11824387
TI  - From the Centers for Disease Control and Prevention. Evaluation of Bacillus
      anthracis contamination inside the Brentwood mail processing and distribution
      center--District of Columbia, October 2001.

PMID- 11824388
TI  - JAMA patient page. Rubella.

PMID- 11824390
TI  - Point-counterpoint: what is the optimal trial design to test hyperthermia for
      carcinoma of the cervix? Point: addition of hyperthermia or cisplatin to
      radiotherapy for patients with cervical cancer; two promising combinations--no
      definite conclusions.
AB  - Randomized trials have shown that results of radiotherapy in patients with
      cervical cancer can be improved by combining the treatment with either cisplatin
      based chemotherapy, or hyperthermia. The studies on both the combination of
      radiotherapy with chemotherapy, and the combination on radiotherapy with
      hyperthermia, leave several important questions unanswered. At present, no
      definite conclusions can be drawn with regard to which combination results in the
      best therapeutic ratio. Therefore, on both ethical and scientific grounds, the
      next logical step would be to compare the two types of combined treatment to each
      other, and each combination with a treatment including all three modalities, in a
      randomized fashion.

PMID- 11824391
TI  - [A preliminary form of 3-dimensional color systems in Rubens' illustrated
      textbook of Franciscus Aguilonius (1613)].

PMID- 11824392
TI  - Detection of swallowing sounds: methodology revisited.
AB  - Cervical auscultation is in the process of gaining clinical credibility. In order
      for it to be accepted by the clinical community, the procedure and equipment used
      must first be standardized. Takahashi et al. [Dysphagia 9:54-62, 1994] attempted
      to provide benchmark methodology for administering cervical auscultation. They
      provided information about the acoustic detector unit best suited to picking up
      swallowing sounds and the best cervical site to place it. The current
      investigation provides contrasting results to Takahashi et al. with respect to
      the best type of acoustic detector unit to use for detecting swallowing sounds.
      Our study advocates an electret microphone as opposed to an accelerometer for
      recording swallowing sounds. However, we agree on the optimal placement site. We
      conclude that cervical auscultation is within reach of the average dysphagia
      clinic.

PMID- 11824393
TI  - Enantiomeric determination of pantoprazole in human plasma by multidimensional
      high-performance liquid chromatography.
AB  - Multidimensional HPLC is a powerful tool for the analysis of samples of a high
      degree of complexity. This work reports the use of multidimensional HPLC by
      coupling a RAM column with a chiral polysaccharide column to the analysis of
      Pantoprazole in human plasma by direct injection. The enantiomers from the plasma
      samples were separated with high resolution on a tris(3,5
      dimethoxyphenylcarbamate) of amylose phase after clean-up by a RAM BSA octyl
      column. Water was used as solvent for the first 5 min in a flow-rate of 1.0
      ml/min for the elution of the plasmatic proteins and then acetonitrile-water
      (35:65 v/v) for the transfer and analysis of pantoprazole enantiomers, which were
      detected by UV at 285 nm. Analysis time was 28 min with no time spent on sample
      preparation. A good linear relationship was obtained in the concentration range
      of 0.20 to 1.5 microg/ml for each enantiomer. Inter and intra-day precision and
      accuracy were determined by one low (0.24 microg/ml), one medium (0.70 microg/ml)
      and one high (1.3 microg/ml) plasma concentration and gave a C.V. varying from
      1.80 to 8.43% and accuracy from 86 to 92%. Recoveries of pantoprazole enantiomers
      were in the range of 93.7-101.2%. The validated method was applied to the
      analysis of the plasma samples obtained from ten Brazilian volunteers who
      received an 80 mg oral dose of racemic pantoprazole and was able to quantify the
      enantiomers of pantoprazole in all clinical samples analyzed.

PMID- 11824394
TI  - Rapid and simple high-performance liquid chromatographic assay for the
      determination of metformin in human plasma and breast milk.
AB  - A rapid and simple high-performance liquid chromatographic (HPLC) assay for the
      determination of metformin in human plasma and breast milk is described. After
      proteins were precipitated with acetonitrile, metformin and the internal standard
      buformin were resolved on a cation-exchange column and detected by UV detection
      at 236 nm. Standard curves were linear over the concentration range 20.0-4000
      microg/l. Intra- and inter-day coefficients of variation were <9.0% and the limit
      of quantification was around 20 microg/l.

PMID- 11824395
TI  - Physical and rheological characterisation of polyethylene glycol-cashew-nut tree
      gum aqueous two-phase systems.
AB  - The characterisation of the polyethylene glycol-cashew-nut tree gum aqueous two
      phase system is described. Factors which affect the phase diagram including
      polymer molecular mass, pH and temperature were analysed. The physico-chemical
      properties of the system such as density, viscosity, volume ratio and phase
      separation times were also described. The characteristics of the system studied
      indicate it to be very attractive as a separation technique.

PMID- 11824396
TI  - Feasibility of the direct coupling of solid-phase extraction-pipette tips with a
      programmed-temperature vaporiser for gas chromatographic analysis of drugs in
      plasma.
AB  - Solid-phase extraction-pipette tips (SPE-PTs) were used for micro solid-phase
      extraction of lidocaine and diazepam from plasma. Off-line extraction was
      followed by on-line desorption. On-line desorption was carried out by direct
      coupling of the SPE-PTs with the liner of the programmed-temperature vaporiser.
      This coupling only required shortening of the liner by maximally 16 mm, cutting
      the SPE-PT, and equipping the remaining part with two O-rings. Due to the heating
      of the injector the SPE-PTs were heated as well, which resulted in a significant
      amount of impurities. Pre-heating and pre-washing was performed prior to the
      extraction to reduce the impurity level. The internal coupling device was applied
      successfully for the analysis of plasma samples with gas chromatography (GC) and
      mass-selective detection. Detection limits of 0.75 ng/ml and 2.5 ng/ml were
      obtained for lidocaine and diazepam, respectively, using 200 microl plasma.
      Recoveries for both compounds were about 80%. Although it is possible, the
      internal coupling device was not developed to be used as such. The main goal of
      this coupling was to show the feasibility of the integration of SPE-PTs with GC
      and to realize an important step to new automated SPE-GC systems.

PMID- 11824397
TI  - [Commemorative medal: Dr. Geza Dabasi Halasz].

PMID- 11824398
TI  - [About plastic surgery of saddle nose. 1901].

PMID- 11824399
TI  - Comparative non-shivering thermogenesis in adjacent populations of the common
      spiny mouse (Acomys cahirinus) from opposite slopes: the effects of increasing
      salinity.
AB  - We compared non-shivering thermogenesis between two adjacent populations of the
      common spiny mouse Acomys cahirinus from different habitats, in relation to
      increasing salinity. Individuals were captured from the north- and south-facing
      slopes of the same valley, that represent "Mediterranean" and "desert" habitats,
      respectively. We hypothesized that the two populations of mice would differ in
      their thermoregulatory capacities, reflecting their need to cope with the
      environmental stress in each habitat. We measured resting metabolic rate by
      recording oxygen consumption, body temperature and response to an injection of
      exogenous noradrenaline. Mice were maintained on diets with increasing levels of
      salt intake to examine their abilities to cope with increasing osmotic stress.
      Mice from north-facing slopes generally had a higher resting metabolic rate and a
      higher increase in oxygen consumption in response to noradrenaline than mice from
      south-facing slopes. Increasing salinity decreased resting metabolic rate values,
      body temperature, and oxygen consumption in response to noradrenaline in both
      populations, and diminished slope-dependant differences. We suggest that these
      differences could be a result of an ongoing adaptive process to different
      climatic conditions, typical of the Mediterranean region, that are a demonstrable
      example of evolution in action.

PMID- 11824400
TI  - The effects of thyroxine on metabolism and water balance in a desert-dwelling
      rodent, Merriam's kangaroo rat (Dipodomys merriami).
AB  - Desert-dwelling mammals such as Merriam's kangaroo rat (Dipodomys merriani) need
      to conserve both energy and water to survive desert conditions characterized by
      aridity and low productivity. The thyroid hormone thyroxine increases both basal
      metabolic rate and urinary water loss in mammals. Increases in basal metabolism
      and urinary water loss are likely to be detrimental to D. merriami, therefore the
      regulation of this hormone may be important. To examine the effects of thyroxine
      in this species, we implanted adult kangaroo rats with pellets designed to
      release specific doses of thyroxine at a constant rate for 90 days or a placebo
      pellet. We measured plasma thyroxine concentration, basal metabolic rate, food
      consumption, urine concentration and water loss in all implanted animals.
      Thyroxine implants significantly increased both plasma thyroxine and basal
      metabolic rate in a relatively dose-dependent manner. In response to thyroxine.
      kangaroo rats increased food consumption only slightly, but this small increase
      was sufficient to compensate for their elevated metabolic rates. Neither urine
      concentration nor water loss varied among treatment groups. Thyroxine increased
      energy expenditure but not water loss in this species.

PMID- 11824401
TI  - Variation in plasma leptin levels in response to fasting in Antarctic fur seals
      (Arctocephalus gazella).
AB  - Plasma leptin levels were determined in 8 lactating female and 20 pup Antarctic
      fur seals (Arctocephalus gazella) during fasting periods of normal duration.
      Plasma leptin levels ranged from 1.35 3.19 ng x ml(-1) in lactating females and
      1.79-4.80 ng x ml(-1) in pups and were not positively correlated with body mass
      or condition. A negative trend, however, was observed between plasma leptin
      levels and body condition in lactating females upon their arrival at the colony
      following a foraging trip (beginning of fast). In accordance with findings in
      other species, plasma leptin levels dropped significantly (P < 0.02) in response
      to the 17-19% drop in body mass experienced by pups during fasting. In contrast,
      plasma leptin levels in lactating females increased during the first 24 h of
      fasting before decreasing throughout the remaining 48 h of the fast. This
      unexpected result could be due to the high level of energy expenditure by seals
      as they swim back to the colony (i.e. post-exercise response) or may be
      influenced by the intense suckling activity experienced by females during the
      onshore fasting periods. The results of this study support recent findings in
      other carnivore species which suggest the primary physiological role of leptin in
      these species may not necessarily be as a signal of the magnitude of body energy
      reserves.

PMID- 11824403
TI  - Body temperature patterns before, during, and after semi-natural hibernation in
      the European ground squirrel.
AB  - Ground squirrels undergo extreme body temperature fluctuations during
      hibernation. The effect of low body temperatures on the mammalian circadian
      system is still under debate. Using implanted temperature loggers, we recorded
      body temperature patterns in European ground squirrels kept in an enclosure under
      natural conditions. Although hibernation onset was delayed, hibernation end
      corresponded closely to that measured in a field population. Circadian body
      temperature fluctuations were not detected during deep torpor, but indications of
      circadian timing of arousal episodes at higher temperatures were found at the
      beginning and end of hibernation. One male exhibited synchronised arousals to a
      relatively constant phase of the day throughout hibernation. All animals first
      entered torpor in the afternoon. Daily body temperature fluctuations were
      decreased or distorted during the first days after hibernation. We hypothesise
      that hibernation may affect the circadian system by either decreasing the
      expression of the circadian oscillator, or by decreasing the amplitude of the
      circadian oscillator itself. possibly due to gradual, temperature dependent,
      internal desynchronisation. The latter mechanism may be beneficial because it
      might facilitate post-hibernation re-entrainment rates.

PMID- 11824402
TI  - Salivary secretion during selective beta-adrenoreceptor stimulation and blockade
      in the parotid gland of red kangaroos, Macropus rufus.
AB  - Intracarotid infusions of noradrenaline (0.3 nmol.kg(-1) x min(-1)) stimulated
      salivary fluid secretion and caused increases in salivary concentrations of
      protein, potassium. magnesium. chloride and phosphate, and decreases in
      bicarbonate. These effects of intracarotid noradrenaline were not reduced by
      simultaneous intracarotid infusion of phentolamine (3.0 nmol.kg(-1) x min(-1))
      but were significantly greater than the responses accompanying intravenous
      noradrenaline infusion. Concomitant administration of the beta-antagonist,
      CGP20712A, were much more effective in blocking the noradrenaline-induced changes
      in salivary composition than equimolar infusions of the beta2-antagonist,
      ICI118551, thereby confirming the presence of beta1-adrenoreceptors. Intracarotid
      infusion of salbutamol at 0.6 nmol x kg(-1) x min(-1) and 6.0 nmol x kg(-1) x
      min(-1) caused increasing but qualitatively similar changes in salivary
      composition to intracarotid noradrenaline but was less effective than
      noradrenaline in augmenting salivary protein release. Equimolar intravenous
      infusions of salbutamol and noradrenaline were equally potent in altering
      salivary electrolyte concentrations but salbutamol by this route had less effect
      on protein release and fluid secretion. Concurrent intravenous and intracarotid
      infusions of beta1-(CGP) and beta2-(ICI) antagonists with intracarotid salbutamol
      showed that the beta2-antagonist was more potent than the beta1-antagonist by the
      intracarotid route thereby demonstrating the presence of glandular beta2
      receptors and eliminating the possibility that the response to salbutamol was due
      totally by reflex increases in general sympathetic tone triggered by lowered
      blood pressure. It was concluded that the kangaroo parotid has functional beta1-
      and beta2-adrenoreceptor subtypes in endpieces whereas the data provide little
      support for either adrenoreceptor subtype being present in the excurrent duct
      system.

PMID- 11824404
TI  - Reproductive activity influences thermoregulation and torpor in pouched mice,
      Saccostomus campestris.
AB  - The Afrotropical pouched mouse Saccostomus campestris displays sexual disparity
      in the use of daily torpor; males reluctantly enter torpor. We tested the
      hypothesis that males may compensate for a limited heterothermic capacity with
      lower basal and resting metabolic rates relative to females. We also investigated
      the association between gonadal activity (testosterone) and the propensity for
      daily torpor. Body temperature and oxygen consumption were measured at various
      ambient temperatures and were compared between sexes under ad libitum and
      restricted-diet treatments. Whereas no significant sex differences were observed
      in body temperature and oxygen consumption under ad libitum treatment, there were
      pronounced differences in heterothermic responses under food restriction. Females
      employed torpor more frequently and also had lower minimum torpor body
      temperatures (ca. 25 degrees C) than males (ca. 29 degrees C). Testosterone
      inhibited torpor in males, whereas the majority of saline-treated animals
      employed torpor under both ad libitum and restricted-diet treatments. This study
      demonstrated that the limited capacity of male S. campestris to enter torpor is a
      consequence of reproductive activity and that opportunistic breeding and the
      absence of seasonal testes regression compromises the capacity to conserve energy
      through daily torpor.

PMID- 11824405
TI  - Freezing survival, body ice content and blood composition of the freeze-tolerant
      European common lizard, Lacerta vivipara.
AB  - To investigate the freeze tolerance of the European common lizard, Lacerta
      vivipara, we froze 17 individuals to body temperatures as low as -4 degrees C
      under controlled laboratory conditions. The data show that this species tolerates
      the freezing of 50% of total body water and can survive freezing exposures of at
      least 24-h duration. Currently, this represents the best known development of
      freeze tolerance among squamate reptiles. Freezing stimulated a significant
      increase in blood glucose levels (16.15+/- 1.73 micromol x ml(-1) for controls
      versus 25.06 +/- 2.92 micromol x ml(-1) after thawing) but this increase had no
      significant effect on serum osmolality which was unchanged between control and
      freeze-exposed lizards (506.0 +/- 23.8 mosmol x l(-1) versus 501.0 +/- 25.3
      mosmol x l(-1), respectively). Tests that assessed the possible presence of
      antifreeze proteins in lizard blood were negative. Recovery at 5 degrees C after
      freezing was assessed by measurements of the mean time for the return of
      breathing (5.9 +/- 0.5 h) and of the righting reflex (44.8 +/- 4.5 h). Because
      this species hibernates in wet substrates inoculative freezing may frequently
      occur in nature and the substantial freeze tolerance of this lizard should play a
      key role in its winter survival.

PMID- 11824407
TI  - Adrenergic receptors, Na+/H+ exchange and volume regulation in lungfish
      erythrocytes.
AB  - Aestivation in African and South American lungfish (Protopterus and Lepidosiren,
      respectively) is associated with elevations of extracellular osmolarity. Osmotic
      shrinkage of Protopterus red blood cells (RBCs) caused a small but significant
      stimulation of the Na influx that was amiloride-sensitive. suggesting involvement
      of the Na+/H+ exchanger (NHE). The associated in vitro regulatory volume increase
      was insignificant within a time frame of 120 min, but the shrinkage-activated Na+
      influx may be sufficient for slow regulatory volume increase during aestivation
      in vivo. Osmotic swelling of the RBCs induced an incomplete regulatory volume
      decrease that was statistically significant after 180 min. The RBCs of
      Protopterus were very large (mean cellular volume of 6939 +/- 294 microm3) and
      possessed 23,066 +/- 7,326 beta-adrenoceptors cell(-1) with a Kd value of 6.1 +/-
      3.2 nM. The number of receptors per unit surface area of lungfish RBCs was
      calculated to be twice that of trout RBCs and 70% that of cod RBCs. There was,
      however, no adrenergic stimulation of the NHE in either Protopterus or
      Lepidosiren. Acidification of the extracellular medium also failed to activate
      the NHE.

PMID- 11824408
TI  - [Infant care in ancient Rome].
AB  - Children are seldom spoken of in Roman times. We know about medicine since long
      before the birth of Christ but it's not until the first century AD that there is
      a book that concerns with the nursing of a newborn child. The book is called
      Gynaecia and was written by Soranus who had studied medicine in Alexandria before
      he arrived at Rome. Soranus gives distinctive advice about the care of the
      newborn baby, especially when he talks about the wet-nurse. It seems that nearly
      none is good enough. Many of Soranus' advice about daily care of the baby
      remembers of the routines of the neonatal care of today, NIDCAP.

PMID- 11824406
TI  - An investigation of carbonic anhydrase activity in the gills and blood plasma of
      brown bullhead (Ameiurus nebulosus), longnose skate (Raja rhina), and spotted
      raffish (Hydrolagus colliei).
AB  - Separated plasma and whole blood non-bicarbonate buffering capacities, together
      with plasma and gill carbonic anhydrase activities and endogenous plasma carbonic
      anhydrase inhibitor activity were investigated in three species of fish: the
      brown bullhead (Ameirus nebulosus), a teleost; the longnose skate (Raja rhina),
      an elasmobranch; and the spotted ratfish (Hydrolagus colliei), a chimaeran. The
      objective was to test the hypothesis that species possessing gill membrane-bound
      carbonic anhydrase and/or plasma carbonic anhydrase activity would also exhibit
      high plasma nonbicarbonate buffering capacity relative to whole blood non
      bicarbonate buffering capacity and would lack an endogenous plasma carbonic
      anhydrase inhibitor. Separated plasma non-bicarbonate buffering capacity
      constituted > or = 40% of whole-blood buffering in all three species. In
      addition, all species lacked an endogenous plasma carbonic anhydrase inhibitor.
      Separated plasma from skate and ratfish contained carbonic anhydrase activity,
      whereas bullhead plasma did not. Examination of the subcellular distribution and
      characteristics of branchial carbonic anhydrase activity revealed that the
      majority of branchial carbonic anhydrase activity originated from the cytoplasmic
      fraction in all species, with only 3-5% being associated with a microsomal
      fraction. The microsomal carbonic anhydrase activity of bullhead and ratfish was
      significantly reduced by washing, indicating the presence of carbonic anhydrase
      activity that was not integrally associated with the membrane pellet, microsomal
      carbonic anhydrase activity in skate was unaffected by washing. In addition,
      microsomal carbonic anhydrase activity from skate and ratfish but not bullhead
      gills was released to a significant extent from its membrane association by
      treatment with phosphatidylinositol-specific phospholipase C. The results
      obtained for skate are consistent with published data for dogfish, suggesting
      that the possession of branchial membrane-bound carbonic anhydrase activity may
      be a generalised elasmobranch characteristic. Ratfish, which also belong to the
      class Chondrichthyes, exhibited a similar pattern. Unlike skate and ratfish,
      bullhead exhibited high plasma non-bicarbonate buffering capacity and lacked an
      endogenous carbonic anhydrase inhibitor in the absence of plasma and gill
      membrane-bound carbonic anhydrase activities.

PMID- 11824409
TI  - [Poul Bjerre's practice of psychiatry].
AB  - Poul Bjerre (1876-1964) was one of Swedens most famous psychiatrists and authors
      in the first part of the 20th century. He had an extensive medical practice. This
      study is mainly based on letters from patients to Bjerre. These letters are now
      kept in The Royal Library, Stockholm. The aim of the study was to find out what
      made Poul Bjerre a successful practitioner. The letters was studied with a
      phenomenological-hermeneutical approach. The results highlights the importance
      and need for the physician to be human, to talk with and listen to the patient in
      a holistic manner, to use words with great care and to touch the patient. This
      led to understanding, and the physician was regarded a friend and someone who one
      could tell anything. Bjerre acted in a time of paternalism, but used this to
      release autonomy for the patient, so that he could be liberated. Follow up was
      very important, mainly through letters.

PMID- 11824410
TI  - [Studies of vision by Leonardo da Vinci].
AB  - Leonardo was an advocate of the intromission theory of vision. Light rays from
      the object to the eye caused visual perceptions which were transported to the
      brain ventricles via a hollow optic nerve. Leonardo introduced wax injections to
      explore the ventricular system. Perceptions were assumed to go to the "senso
      comune" in the middle (3rd) ventricle, also the seat of the soul. The processing
      station "imprensiva" in the anterior lateral horns together with memory "memoria"
      in th posterior (4th) ventricle integrated the visual perceptions to visual
      experience. - Leonardo's sketches with circular lenses in the center of the eye
      reveal that his dependence on medieval optics prevailed over anatomical
      observations. Drawings of the anatomy of the sectioned eye are missing although
      Leonardo had invented a new embedding technique. In order to dissect the eye
      without spilling its contents, the eye was first boiled in egg white and then
      cut. The procedure was now repeated and showed that the ovoid lens after boiling
      had become spherical. - Leonardo described that light rays were refracted and
      reflected in the eye but his imperfect anatomy prevented a development of
      physiological optics. He was, however, the first to compare the eye with a pin
      hole camera (camera obscura). Leonardo's drawings of the inverted pictures on the
      back wall of a camera obscura inspired to its use as an instrument for artistic
      practice. The camera obscura was for centuries a model for explaining human
      vision.

PMID- 11824411
TI  - [Virchow and the cancer of Frederick III].
AB  - Friedrich Wilhelm, born 1831, was the eldest son of Wilhelm I, king of Prussia
      1861 and the first German emperor 1871. He was educated in European culture and
      decided liberal in his political way of thinking and came in opposition to his
      father, the soldier-king and to the "iron-chancellor" Bismarck, who had the
      dominant influence over his father and over German politics. One of Friedrich
      Wilhelms political sympathizer was Rudolf Virchow, the great pathologist, who was
      also a liberal member of parliament in Prussia and later in Germany. He opposed
      Bismarcks war-policy, argued in favour of a peaceful unifying of Germany and
      fought for parliamentary influence on politics and the responsibility of
      ministers to parliament. Friedrich Wilhelm was doomed to remain crown prince
      without influence for most of his life, since his father lived unto 91 years of
      age. The year before he succeeded his father as emperor Friedrich III, he became
      hoarse and the doctors i.e., the English laryngologist Mackenzie inspected his
      vocal cords and took a biopsy, which Virchow diagnosed as a benignant
      inflammatory reaction. Later on it became apparent that the crown prince suffered
      from cancer. He declined a radical operation as too risky but was soon compelled
      to have a tracheotomy performed, when he was on the point of being choked by the
      cancer. During his 99 days as emperor he could only communicate by writing, and
      he had not power enough left to fulfill his intention to dismiss Bismarck and
      initiate a liberal policy, including friendship with England - his beloved wife
      was the eldest daughter of queen Victoria. After his death his son, emperor
      Wilhelm II, took a quite different course, that led to World War I. If Friedrich
      III had been a less intensive smoker and not developed cancer, world history
      might have taken a different course.

PMID- 11824412
TI  - [The rise and fall of the general pediatric practitioner in Sweden].
AB  - At the end of the 1960s the Minister of Health in Sweden became interested in the
      way Czechoslovakia had organised the care of both healthy and sick children with
      one general pediatric practitioner for every 1500 children. After thorough
      investigation The National Board of Health and Welfare in Sweden proposed that
      outpatient pediatric care be integrated with health care both of pre-school- and
      of school children. It was stated by The National Board of Health and Welfare
      that it would be sufficient with one pediatrician for 2500 children, since highly
      qualified pediatric nurses were employed both at the well-baby clinics and in the
      schools. Thus it was calculated that 700 pediatricians would be needed in primary
      care in Sweden. This proposal was received in a positive way and in many counties
      it was planned that specialists in pediatrics should be in charge of the children
      in pediatric outpatient clinics. However, in the aftermath of the events of 1968,
      the opinion changed during the 1970s. The revolutionary groups that wanted to
      destruct the society in order to create something new did not want to have reform
      proposals that they regarded as cosmetics. Science was considered anti-social and
      professionalism was viewed highly suspect. Specialists were looked down upon,
      both within the health profession and elsewhere. The institutions and their
      representatives were not unaffected by these sentiments. The Swedish Medical
      Association, that from the beginning had applauded the counties that had planned
      to follow the proposal from The National Board of Health and Welfare, did a right
      about turn under the pressure of the general practitioners who did not want to
      abstain from the children? "this nice group of patients". In 1974 the Swedish
      Medical Association declared that pediatricians should not be active in primary
      care. Also The National Board of Health and Welfare became influenced by the
      spirit of the times and thus, in 1978, decided that a substantially lower number
      of pediatricians should be trained than they had earlier planned. At that stage,
      many of the counties changed their plans regarding pediatric care to be benefit
      of the general practitioners. Altogether well over 200 positions for general
      pediatric practitioners were established. At the turn of the millennium, this
      number remains virtually unchanged. Some counties have a very well established
      pediatric cae, whereas others do not have one single pediatrician employed in the
      primary health care. However, it presently seems that the general opinion in this
      regard is changing. There is a growing consciousness that children are in need of
      professional medical care as the status of children during the 1990s has steadily
      deteriorated because of e.g. immigrations and increasing social inequalities.
      Both the Minister of Health and other influential health care politicians have
      recently claimed the need for pediatricians in primary care. However, during the
      next few years many of the specialists in pediatrics born during the 1940s will
      retire. Therefore a substantial expansion of the education and training of
      pediatricians of utmost importance in order to replace the retired professionals
      and to fill the needs of primary care.

PMID- 11824413
TI  - Saliva promotes Candida albicans adherence to human epithelial cells.
AB  - Adhesion of Candida cells to oral surfaces is an initial event in pathogenesis.
      Since specific immobilized salivary components mediate the binding of Candida
      albicans to hydroxyapatite, we hypothesized that saliva may also promote
      adherence to oral epithelia via a similar mechanism. In an in vitro model, C.
      albicans ATCC 10261 yeast cells adhered in a saturable manner to monolayers of
      three cultured human epithelial cell lines (A549, HEp-2, and HET-1A). The
      addition of whole saliva to the assay promoted the binding of C. albicans to all
      cell lines in a dose-dependent manner, but pre-incubation of the epithelial cells
      with pooled whole saliva had no effect on subsequent adherence. Pre-incubation of
      the yeast cells with pooled whole saliva, however, significantly enhanced (by up
      to 120%, P < 0.05) binding to epithelial cell monolayers, and pooled saliva that
      had been pre-incubated with C. albicans yeast cells was defective in promoting
      yeast adherence. There was a negative correlation (r = 0.68, P < 0.005) between
      specific IgA titers against whole cells of C. albicans and adherence-promoting
      activities for individual saliva samples. The adhesion-inhibitory effect of
      specific anti-C. albicans IgA was reversed by depletion of IgA from saliva by
      affinity chromatography. Factors in whole saliva, therefore, bound to the yeast
      cells, counter the C. albicans-specific salivary IgA inhibitory effect on
      adhesion and promote the adherence of C. albicans yeast cells to cultured
      epithelial cells.

PMID- 11824414
TI  - The microbiota of young children from tooth and tongue samples.
AB  - This study determined the frequency with which 38 microbial species were detected
      in 171 randomly selected children from 6 to 36 months of age. Children were
      sampled and dental caries measured. Oral samples were assayed by means of a
      checkerboard DNA probe assay. The detection frequencies from tongue samples in
      children under 18 mos were: S. mutans 70%, S. sobrinus 72%, P. gingivalis 23%, B.
      forsythus 11%, and A. actinomycetemcomitans 30%, with similar detection
      frequencies in children over 18 mos. Thus, S. mutans and the periodontal
      pathogens, P. gingivalis and B. forsythus, were detected even in the youngest
      subjects. Species associated with caries included S. mutans (children ages 18-36
      mos) and A. israelii (children ages < 18 mos), the latter species possibly
      reflecting increased plaque in children with caries. Species detection from tooth
      and tongue samples was highly associated, with most species detected more
      frequently from tongue than from tooth samples in children under 18 mos,
      suggesting that the tongue was a potential microbial reservoir.

PMID- 11824415
TI  - Levels of GM-CSF, IL-3, and IL-6 in fluid and tissue from human radicular cysts.
AB  - Cytokines released by immune system cells play an important role in cyst
      enlargement. This study aimed to determine, by ELISA, the levels of granulocyte
      macrophage colony-stimulating factor (GM-CSF), interleukin 3 (IL-3), and IL-6 in
      fluid and tissue from human radicular cysts. GM-CSF was found in 42.8% of the
      fluid samples (164.3 pg/mL) and IL-6 in 92.8% (641.4 pg/mL). No IL-3 was detected
      in any fluid samples. In the tissue samples, 28.6% were positive for IL-3 (369.2
      pg/mL), 86.4% for IL-6 (92.4 pg/mL), and 95.8% for GM-CSF (200.5 pg/mL). It can
      be concluded that GM-CSF and IL-6 were widely found in the fluid and tissue
      samples. In contrast, IL-3 was found only in the cystic tissue, even though in
      few lesions. These cytokines may contribute to the inflammation, cystic growth,
      and bone resorption that characterize cystic lesions.

PMID- 11824416
TI  - CYP3A4-mediated hepatic metabolism of the HIV-1 protease inhibitor saquinavir in
      vitro.
AB  - 1. The aim was to identify the major metabolites of saquinavir (SQV) from human
      hepatic microsomal incubations and the CYP isoform(s) responsible. 2. Ten
      fractions containing various metabolites were separated by isocratic reversed
      phase HPLC and characterized by HPLC, mass spectrometry and NMR. 3. Metabolites
      were either mono- or di-hydroxylated derivatives of SQV. Fast-atom bombardment
      and electrospray MS showed that hydroxylation was predominantly situated on the
      decahydroisoquinoline ring. A major metabolite (M4) was rigorously identified as
      6-equatorial-hydroxy SQV. 4. Metabolism of saquinavir to all metabolites was
      inhibited by the CYP3A4-selective inhibitor ketoconazole (IC50 = 0.55 +/- 0.12
      microM). Other isoform-selective inhibitors were non-inhibitory. The protease
      inhibitors ritonavir, indinavir and nelfinavir potently inhibited SQV metabolism
      in hepatic microsomes with IC50 = 0.025 +/- 0.004, 0.82 +/- 0.26 and 0. 58 +/-
      0.14 microM, respectively. 5. Saquinavir metabolism correlated with
      immunochemically determined CYP3A4 levels and testosterone 6beta-hydroxylation,
      but it failed to correlate with either immunochemically determined CYPIA2 levels
      or marker activities for CYP1A2, 2C9 or 2E1. 6. Heterologously expressed CYP3A4
      metabolized saquinavir with a similar metabolic profile to that of human liver
      microsomes. 7. Km, and Vmax for total SQV metabolism were 0.61 +/- 0.19 microM
      and 1.82 +/- 1.13 nmol mg(-1) min(-1), respectively. 8. The extensive involvement
      of hepatic CYP3A4 in the metabolism of saquinavir predicts high intrinsic
      clearance of saquinavir. Inhibitors of CYP3A4 such as other protease inhibitors
      will substantially increase the bioavailability of saquinavir.

PMID- 11824417
TI  - US Food and Drug Administration's Total Diet Study: intake of nutritional and
      toxic elements, 1991-96.
AB  - The Food and Drug Administration (FDA) has conducted the Total Diet Stuty (TDS)
      annually since 1961. The TDS is designed to monitor the US food supply for levels
      of toxic chemical contaminants (pesticide residues, industrial chemicals and
      toxic elements) and nutritional elements. Foods are generally collected four
      times a year, once from each of four regions of the country. The foods are
      prepared table-ready before being analysed. From the results of the TDS, dietary,
      intakes of these analytes are estimated for selected age-sex groups in the US
      population. This paper reports on the dietary intake of 10 nutritional and four
      toxic elements based on measurements made in foods collected in the TDS between
      1991 and late 1996. Average daily intakes were estimated for 14 age-sex groups in
      the US population, as well as the contribution of specific food groups to total
      intakes. For most nutritional elements, teenage boys and adult males had the
      highest daily intakes. Intakes by infants were below the intake references for
      seven of 10 nutritional elements, and young girls and women had inadequate
      intakes of at least half the nutritional elements. Intakes by children between 2
      and 10 years of age, teenage boys, and adult males met or exceeded the reference
      intakes for the majority of nutritional elements. Intakes by all population
      groups were well below the reference intakes for all toxic elements.

PMID- 11824418
TI  - Soapstone (steatite) cookware as a source of minerals.
AB  - Steatite or soapstone, is a soft metamorphic rock composed mainly of talc,
      dolomite and actinolite, which is abundantly found and used for the manufacture
      of cookware in south-east Brazil. The study estimates its usage for cookware
      among dwellers of Ouro Preto, and assesses the possible toxicological or
      nutritional impact on food preparation. Pans made of steatite were purchased both
      in the crude (n = 6) and 'cured'forms (n = 6). Migration of Ca, Fe, Mg, Mn, Co,
      Al, Cr, Ni, Pb and Cd was determined for 20 sequential cooking trials, using 3
      and 5% acetic acid as a food simulant. Analytical determinations were carried out
      by inductively coupled plasma atomic-emission spectrometry and the data treated
      by an individual model of random effects, simple linear regression and Pearson's
      correlation. About 81% of Ouro Preto's native population own soapstone cookware
      and, of these, 79% use the pans regularly. Mineral migration followed the general
      solubility of the crystalline components of the rock. Therefore, Ca, Mg, Fe and
      Mn were, in that order, the elements that exhibited highest migration, whereas
      the remaining were seen in negligible levels, except for Ni in the crude pans.
      The 5% solution favoured migration, whereas curing tended to restrict migration
      and extend durability of the pan. It is concluded that while cured soapstone pans
      do not offer mineral toxicity, they may contribute to the mineral nutrition of
      human beings.

PMID- 11824419
TI  - Copper intrauterine devices and tubal infertility among nulligravid women.

PMID- 11824420
TI  - GB virus C and mortality from HIV infection.

PMID- 11824421
TI  - GB virus C and mortality from HIV infection.

PMID- 11824422
TI  - Cardiac rehabilitation.

PMID- 11824423
TI  - Cephalosporin allergy.

PMID- 11824424
TI  - Cephalosporin allergy.

PMID- 11824425
TI  - The role of colchicine in Helicobacter pylori prevalence and gastric mucosal
      changes in Behcet's Disease.

PMID- 11824426
TI  - Venlafaxine and generalised anxiety disorder: new preparation. Minimise recourse
      to drugs.
AB  - (1) Generalised anxiety disorder is defined as excessive anxiety for at least 6
      months. (2) Management is based primarily on psychological measures, with the aim
      of limiting recourse to drugs. The reference drugs are benzodiazepines. The
      treatment period should be as short as possible, to avoid adverse effects such as
      sedation and dependence. (3) Venlafaxine is a non tricyclic, non MAOI
      antidepressant. A sustained-release formulation has just been granted marketing
      authorisation in France for generalised anxiety disorder. (4) The clinical
      assessment file on venlafaxine in this indication includes results from two 8
      week trials and a placebo-controlled trial with 6 months follow-up. The trials
      showed a significant improvement with venlafaxine on standard anxiety scales, but
      the clinical impact (at best moderate) has been poorly assessed. We found no
      comparison between venlafaxine and benzodiazepines. (5) In one trial venlafaxine
      was no more effective than buspirone. (6) The most frequent adverse effects of
      venlafaxine are gastrointestinal disorders, insomnia and dizziness. Venlafaxine
      carries a risk of drug interactions and withdrawal symptoms. (7) In practice,
      venlafaxine provides nothing new in the treatment of generalised anxiety
      disorder. The reference drug treatment remains a benzodiazepine.

PMID- 11824428
TI  - Sibutramine: new preparation. Slight weight loss; but also a slight rise in blood
      pressure ...
AB  - (1) The reference treatment for achieving weight loss by obese patients is a
      combination of dietary measures, exercise and behavioural interventions. There is
      currently no drug treatment with demonstrated efficacy on the morbidity or
      mortality associated with excess body weight. (2) Sibutramine, a serotonin- and
      noradrenaline-reuptake inhibitor structurally related to the amphetamines has
      been granted marketing authorisation in France for the treatment of obesity and
      excess body weight in patients with associated risk factors. (3) The clinical
      file on sibutramine contains no trial focusing on morbidity or mortality end
      points. (4) According to comparative clinical trials, weight loss during a 6-12
      month course of sibutramine is, on average, between 3 and 9 kg greater than that
      on placebo. Patients regain weight after sibutramine cessation. (5) Sibutramine
      has little or no benefit on blood sugar or lipid parameters. (6) The main known
      adverse effect of sibutramine is increased blood pressure. Sibutramine also has
      amphetamine-like side effects. (7) In practice, sibutramine currently has no
      place in the management of obesity.

PMID- 11824427
TI  - Mifepristone: new preparation. Avoids or facilitates cervical dilatation before
      vacuum aspiration of pregnancy.
AB  - (1) Cervical softening with prostaglandins or laminaria before vacuum aspiration
      of pregnancy can avoid or facilitate mechanical dilatation. (2) Mifepristone is
      now licensed in France for cervical softening before vacuum aspiration of
      pregnancy. (3) The clinical file on mifepristone in this indication contains data
      from about 20 comparative clinical trials using surrogate end points, namely the
      need for and/or ease of cervical dilatation. (4) In these trials the cervix was
      easier to dilate in women who received mifepristone than in women who received a
      placebo. (5) A few comparative trials showed comparable efficacy of
      prostaglandins, laminaria (small hydrophilic stents inserted into the cervix that
      gradually swell, leading to cervical dilatation) and mifepristone in this
      indication. (6) Before vacuum aspiration, metrorrhagia occurred more frequently
      in women on mifepristone than in those on a placebo. Blood losses during vacuum
      aspiration were comparable in women who had received prostaglandins and those who
      had received mifepristone. (7) The incidence of abdominal pain may be lower on
      mifepristone than with laminaria or prostaglandins.

PMID- 11824429
TI  - News of Prescrire's reps monitoring network: pretences and off-label claims.

PMID- 11824430
TI  - Low molecular weight heparin and pregnancy.
AB  - (1) Low molecular weight heparins (LMWH) are increasingly used during pregnancy.
      (2) Clinical data on the use of LMWH during pregnancy are limited. They are drawn
      mainly from heterogeneous case series, most of which were non comparative and
      involved prophylaxis rather than therapy. They provide no clear conclusions as to
      the efficacy and adverse effects of LMWH compared with unfractionated heparin, or
      the optimal dose regimen during the different phases of pregnancy. (3) No risk of
      malformations has been reported with LMWH preparations available in France, but
      data are insufficient to rule out a risk of obstetric, fetal or neonatal
      problems. (4) Cases of intraspinal haematoma have occurred after epidural
      anaesthesia. (5) Unfractionated heparin remains the reference treatment during
      pregnancy.

PMID- 11824431
TI  - Severe liver damage with leflunomide.
AB  - Potentially life-threatening; close monitoring required.

PMID- 11824432
TI  - Severe hepatitis due to Atrium.
AB  - (1) Atrium, a combination of difebarbamate, febarbamate and phenobarbital first
      marketed in France more than 30 years ago, carries a risk of hepatitis. (2)
      Despite restrictions on its indications and treatment duration introduced in
      1997, cases of severe liver damage have continued to be notified in France. (3)
      Benzodiazepines are the reference drugs for alcohol withdrawal. Carbamates and
      barbiturates are no more effective than benzodiazepines, and carry a higher risk
      of adverse effects. (4) The recent decision to withdraw Atrium from the market
      was long awaited.

PMID- 11824433
TI  - Disopyramide: interactions with marcolide antibiotics.
AB  - Cases of severe cardiac arrhythmia and major hypoglycaemia have occurred in
      patients receiving disopyramide simultaneously with some macrolide antibiotics,
      especially erythromycin and clarithromycin.

PMID- 11824434
TI  - Urinary disorders on tramadol.
AB  - Some published cases of difficulty with micturition and urinary retention on
      tramadol resemble adverse effects that are well known to occur with other
      opiates.

PMID- 11824435
TI  - Choosing an anticoagulant during pregnancy: usually heparin.
AB  - (1) The precise risk of deep vein thrombosis during pregnancy is poorly
      documented, particularly among women with a history of thromboembolism. (2)
      Anticoagulant therapy is poorly assessed in pregnant women. (3) Unfractionated
      heparin remains the reference for use during pregnancy, based on extensive
      experience and lack of teratogenicity. (4) Low molecular weight heparins have no
      demonstrated advantage over unfractionated heparin in terms of their risk-benefit
      ratio, but they do have certain practical advantages. (5) Vitamin K antagonists
      such as warfarin carry a risk of fetal toxicity if taken between the 6th and 12th
      weeks of pregnancy (nasal and epiphyseal abnormalities). The latency and duration
      of effects makes them more difficult to use than heparin, especially towards the
      end of pregnancy. However, they seem to be more effective than heparin in
      patients with mechanical cardiac valve prostheses.

PMID- 11824436
TI  - Homeopathic arnica: just a placebo.
AB  - Four placebo-controlled trials of homeopathic dilutions of arnica in treating
      trauma have been sufficiently robust to give interpretable results. In all of
      them homeopathic arnica was no more effective than the placebo.

PMID- 11824437
TI  - Amfebutamone/bupropion for smoking cessation: new preparation. Nicotine
      replacement therapy is safer.
AB  - (1) For smokers who want to quit and who qualify for pharmacological support, the
      various forms of nicotine replacement therapy available in France yield a one
      year cessation rate of about 14-18%, compared to about 10% with placebo. (2)
      Amfebutamone (also known as bupropion) is structurally related to an amphetamine
      psychostimulant. (3) The clinical file mainly contains data from a dose-finding
      study, two placebo-controlled trials, and a trial comparing amfebutamone +
      transdermal nicotine with amfebutamone + transdermal placebo. (4) It has not yet
      been shown that the approved dose regimen of 300 mg/day is more effective than
      150 mg/day, or that the treatment period of 7-9 weeks is optimal. (5) Compared to
      placebo, the one-year cessation rate was only about 13% higher (absolute value)
      in one trial, much less in the dose-finding study (3%), and not determined in the
      other two trials. The trial comparing amfebutamone with nicotine suffers from too
      many methodological weaknesses to show any difference in the efficacy of the two
      drugs. There has been no specific assessment of amfebutamone in patients with
      coronary heart disease. (6) There is no basis for combining amfebutamone with
      nicotine replacement therapy, as there is no evidence of higher efficacy.
      Furthermore, cardiovascular risk may be increased. (7) Amfebutamone can have
      serious adverse effects: the estimated risk is approximately 0.1% for convulsions
      and 3% for potentially severe hypersensitivity reactions. The adverse effects
      seem to be similar to those of appetite-suppressant amphetamines, including
      insomnia, weight loss and hypertension. The possible risk of heart valve disease
      has not been ruled out, because echocardiographic follow-up studies have not been
      done. (8) Potential adverse effects and drug interactions should contraindicate
      the use of amfebutamone by patients with a history of cardiovascular,
      neurological or psychiatric disorders. (9) In practice, when someone needs drug
      support to quit smoking, nicotine replacement therapy should be tried first.

PMID- 11824438
TI  - Topical becaplermin: new preparation. A slight short-term help for some diabetic
      patients.
AB  - (1) The reference curative treatment for chronic ulcers in diabetic patients is
      to avoid pressure on the lesions, and to give appropriate local care. (2) A
      topical gel containing 0.01% becaplermin, a cell growth factor, is now marketed
      in Europe for the treatment of chronic neuropathic ulcers measuring less than 5
      cm2 in diabetic patients. (3) The clinical file mainly comprises four trials, two
      of which were double-blind, testing two concentrations. In the largest trial,
      which gave the most favourable results, the lesions healed completely after 20
      weeks in 50% of patients, compared with 35% of patients who used the excipient
      gel and received local care. (4) The optimal concentration of becaplermin gel is
      not known. Neither is its effect on lesions larger than 5 cm2 or its ability to
      prevent the need for amputation. (5) None of the clinical trials revealed any
      severe adverse effects (particularly tumour growth), but pharmacovigilance data
      are limited. (6) In practice, the very expensive topical becaplermin gel can help
      some patients, in whom it slightly accelerates ulcer healing.

PMID- 11824439
TI  - Oxcarbazepine: new preparation. An alternative to carbamazepine in partial
      epilepsy.
AB  - (1) The reference treatment for partial epilepsy in adults and children is
      carbamazepine. (2) Oxcarbazepine is available in the European Union for the
      treatment of partial epilepsy in adults and children aged over 6 years, alone or
      in combination with other antiepileptic drugs. (3) The clinical file on
      oxcarbazepine monotherapy of recent-onset generalised or partial epilepsy mainly
      contains data from one trial versus carbamazepine, two trials versus phenytoin,
      and one trial versus valproate sodium. In these trials, 52-60% of patients had no
      seizures on oxcarbazepine, a proportion not significantly different from that
      obtained with the comparators. Oxcarbazepine may, in fact, be slightly less
      effective than carbamazepine. (4) For refractory partial epilepsy (especially
      forms refractory to carbamazepine), oxcarbazepine is more effective than a
      placebo, when combined with the inadequately effective treatment, as shown in two
      trials. Two dose-finding studies show that 2 400 mg/day oxcarbazepine is more
      effective than 300 mg/day. (5) In trials comparing single-drug treatments there
      were fewer withdrawals for adverse events among patients on oxcarbazepine than
      among those on carbamazepine or phenytoin. Compared with carbamazepine, the risk
      of cutaneous hypersensitivity reactions seems to be lower with oxcarbazepine,
      while the risk of hyponatraemia is higher. This risk of hyponatraemia
      necessitates laboratory monitoring. (6) The risk of clinically significant
      interactions appears to be lower on oxcarbazepine than on carbamazepine, and is
      limited mainly to combined contraceptives (contraceptive inefficacy) and
      phenytoin. (7) In practice, carbamazepine remains the reference treatment for
      partial epilepsy, but oxcarbazepine is one of several second-line options, either
      alone or in combination with other antiepileptics.

PMID- 11824440
TI  - Zanamivir: a second look. Still no tangible impact on influenza.
AB  - (1) The reference treatment for suspected influenza during outbreaks is simple
      relief of symptoms (fever, rhinitis, headache, myalgia, etc.). (2) According to a
      comparative placebo-controlled trial involving 525 patients with asthma and/or
      chronic obstructive airways disease, and a meta-analysis of 9 trials involving
      patients at risk of complications, zanamivir shortens the duration of symptoms of
      suspected influenza by about a day. But zanamivir has not been shown to reduce
      antibiotic prescribing, or the incidence of complications necessitating
      hospitalisation. (3) Zanamivir has no proven efficacy in preventing the spread of
      influenza by a treated patient. (4) Zanamivir inhalation can induce bronchospasm.
      (5) In practice, prevention through vaccination remains the mainstay of
      management. Symptomatic relief is the only rational therapy for influenza.

PMID- 11824441
TI  - Docetaxel: new preparation. No first-line use in metastatic breast cancer.
AB  - (1) For the treatment of metastatic breast cancer, the reference first-line
      cytotoxic chemotherapy is an anthracycline-based combination such as doxorubicin
      + cyclophosphamide. (2) The clinical file on docetaxel in this indication mainly
      comprises data from a comparative trial of doxorubicin + docetaxel versus
      doxorubicin + cyclophosphamide in 429 patients. (3) In this trial the doxorubicin
      + docetaxel combination failed to increase the duration or quality of survival
      relative to the doxorubicin + cyclophosphamide combination, whereas its adverse
      effect profile was somewhat poorer (notably with a risk of severe neutropenia).
      (4) Docetaxel currently has no place in this setting.

PMID- 11824442
TI  - Galantamine: new preparation. The fourth cholinesterase inhibitor for Alzheimer's
      disease.
AB  - (1) The reference symptomatic treatment for mild to moderate Alzheimer's disease
      is a cholinesterase inhibitor such as donepezil, but efficacy is only moderate
      and only about 10% of those patients treated actually benefit. (2) Galantamine is
      the fourth cholinesterase inhibitor to be marketed in France for Alzheimer's
      disease. The clinical file contains data from five double-blind placebo
      controlled trials lasting 3-6 months, but no data comparing galantamine with
      other drugs. (3) These trials show that about 5-13% of patients treated with
      galantamine may be improved. (4) Adverse effects are very frequent, and are
      similar to those of other cholinesterase inhibitors, i.e. nausea, vomiting,
      diarrhoea, abdominal pain, dyspepsia, etc. (5) For patients who are eligible for
      drug therapy, the reference treatment is still donepezil, for want of anything
      better.

PMID- 11824443
TI  - NSAIDs and heart failure.
AB  - (1) Case reports and epidemiological studies show that nonsteroidal
      antiinflammatory drugs (NSAIDs) can cause or worsen heart failure, though this is
      reversible when the drug is withdrawn. (2) Heart failure can occur or worsen when
      an NSAID (including aspirin) is combined with a diuretic or angiotensin
      converting-enzyme inhibitor (ACE inhibitor). (3) In patients with heart failure,
      the use of NSAIDs, including "specific" COX 2 inhibitors, should be avoided. If
      such treatment is unavoidable, patients must be watched closely for clinical
      worsening.

PMID- 11824444
TI  - Thioridazine and severe cardiac arrhythmia.
AB  - Thioridazine prolongs the QT interval and carries a risk of torsades de pointes.
      Several cases of syncope, cardiovascular collapse and sudden death have been
      published.

PMID- 11824445
TI  - Severe systemic effects with topical fluorouracil.
AB  - Even if the approved dose regimen is followed, use of fluorouracil cream on the
      skin carries a risk of severe systemic effects in some patients.

PMID- 11824446
TI  - In vitro fertilisation: many unknowns.
AB  - (1) More than 36 000 oocyte collection procedures were done in France in 1997.
      The mean clinical pregnancy rate was about 20%, but figures varied widely among
      centres. (2) Ovarian stimulation prior to oocyte harvest is achieved by injecting
      recombinant FSH or hMG, usually together with a Gn-RH antagonist or analogue in
      order to avoid premature ovulation. (3) Ovarian hyperstimulation can be life
      threatening.

PMID- 11824447
TI  - OTA assessments were tailored for Congress.

PMID- 11824448
TI  - Wales is not part of England!

PMID- 11824449
TI  - Evolution of nitrogen fixation.

PMID- 11824450
TI  - A history and perspective on direct-to-consumer promotion.

PMID- 11824451
TI  - Medical device labeling and advertising: an overview.
AB  - The Food and Drug Administration (FDA) has the authority under the Federal Food,
      Drug, and Cosmetic Act (FDCA) to regulate the labeling of all medical devices.
      This statement, however, is not as simple as it appears. The regulation of
      medical device labels and labeling, closely linked to the advertisement of
      medical devices, is a dynamic area, and FDA is struggling to address the new
      issues that arise daily in this area. This article seeks to: 1) provide the
      background necessary to understand the current law and FDA's regulation of
      medical devices; 2) summarize the law and regulations governing medical devices;
      3) define "intended use" and explain its importance; and 4) discuss several areas
      that are of particular interest to FDA, including promotion of uncleared or
      unapproved devices and uses, Internet promotion, press releases, and comparative
      claims.

PMID- 11824452
TI  - Devaluing truth: unverified health claims in the aftermath of Pearson v. Shalala.

PMID- 11824453
TI  - FDA marketing v. First Amendment: Washington Legal Foundation legal challenges to
      off-label policies may force unprecedented changes at FDA.

PMID- 11824454
TI  - Guidelines for the promotion of dietary supplements: examining government
      regulation five years after enactment of the Dietary Supplement Health and
      Education Act of 1994.

PMID- 11824455
TI  - DSHEA's third-party literature exemption; mail order sales, direct marketing, and
      Internet use.
AB  - This article examines ways in which marketers of dietary supplements can make use
      of the "third-party literature" section of the Dietary Supplement Health and
      Education Act of 1994 (DSHEA). This provision permits persons or entities, other
      than manufacturers or distributors, to distribute to consumers certain
      publications in connection with the sale of particular supplements. These
      publications may include statements about the therapeutic benefits of such
      products without subjecting the products to regulation by the Food and Drug
      Administration (FDA) as unapproved new drugs. Specifically, this article
      addresses the following: Can a dietary supplement manufacturer or distributor
      send third-party literature about a dietary supplement to a customer in a mail
      order sales transaction? Can third-party literature be disseminated by mail with
      dietary supplement catalogues only? Can third-party literature be disseminated by
      sales representatives engaged in direct marketing of dietary supplements? Can
      third-party literature appear on the Internet? The answer appears to be
      affirmative in each of these situations.

PMID- 11824456
TI  - DSHEA provisions confine FDA's authority to issue regulations that concern
      allegedly adulterated dietary supplements.

PMID- 11824457
TI  - Regulating drug promotion on the Internet.

PMID- 11824458
TI  - Regulation of dietary supplements: five years of DSHEA.

PMID- 11824459
TI  - Is it worth the trouble? The new policy on dissemination of information on off
      label drug use under the Food  and Drug Administration Modernization Act of 1997.

PMID- 11824460
TI  - Special labeling requirements for genetically engineered food: how sound are the
      analytical frameworks used by FDA and food producers?

PMID- 11824461
TI  - The case for a substantial evidence amendment to the informal rulemaking
      provision of the Federal Food, Drug, and Cosmetic Act.

PMID- 11824463
TI  - PBMs and a Medicare prescription drug benefit.

PMID- 11824462
TI  - Biotechnology and the food label: a legal perspective.

PMID- 11824464
TI  - Pharmaceutical patent settlements: the antitrust risks.

PMID- 11824465
TI  - The international harmonization of human tissue regulation: regulatory control
      over human tissue use and tissue banking in select countries and the current
      state of international harmonization efforts.

PMID- 11824466
TI  - A comparison of United States and Canadian laws as they affect generic
      pharmaceutical market entry.

PMID- 11824467
TI  - Challenging the viability of FDCA-based causes of action in the tort context: the
      orthopedic bone screw experience.

PMID- 11824468
TI  - Defining "least burdensome means" under the Food and Drug Administration
      Modernization Act of 1997.

PMID- 11824469
TI  - Access to pharmaceuticals under Medicaid managed care: federal law compiled and
      state contracts compared.

PMID- 11824471
TI  - Regulation of extracellular matrix remodeling and MMP-2 activation in cultured
      rat adrenal medullary endothelial cells.
AB  - We previously reported that short term exposure of cultured rat adrenal medullary
      endothelial cells (RAMEC) to thrombin enhances the subendothelial deposition of
      extracellular matrix (ECM) proteins fibronectin, laminin, and collagen types I (C
      I) and IV (C-IV) (Papadimitriou et at., 1997). In this work, we extended our
      previous studies on factors that affect ECM protein deposition to include agents
      that activate or inhibit some of the most common intracellular signals such as
      cAMP, protein kinase C (PKC) and calcium. Furthemore, we investigated the
      possible link between the observed alterations in ECM protein deposition and the
      secretion of matrix metalloproteinase-2 (MMP-2). Forskolin (adenylyl cyclase
      activator) caused a dose-dependent increase in the deposition of all four ECM
      proteins studied. Isoproterenol (beta-adrenergic receptor agonist) and the
      membrane-permeant cAMP analogue dibutyryl-cAMP, significantly increased the
      deposited amounts of ECM proteins at low concentrations, and this increase was
      reversed at higher concentrations of both agents. All these agents had the
      opposite effect on MMP-2 secretion, increasing it at doses where they decreased
      ECM protein deposition and vice-versa. However, elevation of cAMP by the
      phosphodiesterase inhibitor IBMX had no effect neither on the deposited amounts
      of any of the ECM proteins studied nor on MMP-2 secretion. Activation of PKC by
      phorbol ester (PMA) resulted in a decrease in ECM protein deposition and an
      increase in MMP-2 secretion. Finally, chelation of intercellular calcium with
      BAPTA-AM resulted in an increased ECM deposition and a decrease in MMP-2
      secretion, Our results show a complex pattern of regulation of ECM protein
      deposition by cAMP-mobilizing agents, and also indicate an inverse correlation
      between ECM protein deposition and secretion of MMP-2. The concerted regulation
      of both these processes is essential in the formation of new blood vessels and
      for the integrity of the vascular wall.

PMID- 11824470
TI  - Effects of first generation E1E3-deleted and second generation E1E3E4
      deleted/modified adenovirus vectors on human endothelial cell death.
AB  - Adenoviral vectors are promising tools for pulmonary vascular gene transfer. In
      first generation vectors, the viral E4 region is preserved (E4+ Ad), but E4 is
      deleted in second generation vectors (E4- Ad). These vectors were compared for
      their toxicity in human endothelial cells in terms of apoptosis and necrosis.
      Infection with E4+ Ad vectors reduced whereas E4- Ad vectors enhanced apoptosis
      under normal culture conditions. Furthermore, E4+ Ad protected against apoptosis
      induced by growth factor deprivation, while E4- Ad enhanced apoptosis triggered
      by ceramide. Ad vectors containing different E4 open reading frames, alone or in
      different combinations, showed similar effects to E4- Ad, leaving the viral genes
      that might be responsible for reducing apoptosis unidentified at the present
      time. As previously observed with E4+ Ad devoid of transgene, E4+ Ad carrying
      beta-galactosidase or green fluorescent protein under the control of either the
      RSV or CMV promoter also reduced apoptosis triggered by growth factor
      deprivation. In contrast, E4+ Ad containing a CFTR expression cassette did not
      reduce apoptosis, and E4- Ad with CFFR showed increased toxicity. We conclude
      that Ad vectors may have important effects on the control of apoptosis in
      transfected cells, depending on the residual expression of viral genes. This
      effect can be complicated by the action of transgene expression on cell survival.

PMID- 11824472
TI  - Modulation of angiogenesis and progelatinase a by thrombin receptor mimetics and
      antagonists.
AB  - The angiogenic action of thrombin has been shown to be mediated by activation of
      the thrombin receptor. In this report we studied the effects of SFLLR, an agonist
      of the activated thrombin receptor and thrombin receptor peptide and non peptide
      antagonists on angiogenesis in the chick chorioallantoic membrane (CAM) system.
      As antagonists were used the tripeptide FPR and non-peptide 1,4-disubstituted
      piperazine derivatives. The pentapeptide SFLLR, like thrombin, caused a marked
      stimulation of angiogenesis in the CAM. FPR and the piperazine derivatives caused
      suppression of angiogenesis and in combination with thrombin antagonized its
      angiogenic effect. Thrombin and SFLLR activated progelatinase A (MMP-2) in the
      culture medium of human umbilical cord endothelial cells (HUVECs). MMP-2 is
      involved in the early steps of angiogenesis leading to local dissolution of
      basement membrane collagen and migration of the activated endothelial cells. FPR
      and the piperazine derivatives inhibited the activation of this enzyme. They also
      antagonised the effects of both thrombin and SFLLR on MMP-2 activation. These
      results suggest that non-thrombogenic agonists or antagonists of the activated
      thrombin receptor can be used as modulators of angiogenesis.

PMID- 11824473
TI  - Lipid polarity in brain capillary endothelial cells.
AB  - Brain capillary endothelial cells (BCEC) represent an epithelial like cell type
      with continuous tight junctions and polar distributed proteins. In this paper we
      investigated whether cultured BCEC show a polar distribution of membrane lipids
      as this was demonstrated for many epithelial cell types. Therefore we applied a
      high yield membrane fractionation method to isolate pure fractions of the apical
      and the basolateral plasma membrane (PM) domains. Using a set of methods for
      lipid analysis we were able to determine the total lipid composition of the whole
      cells and the PM fractions. Both membrane domains showed a unique lipid
      composition with clear differences to each other and to the whole cell
      composition. Three lipid species were polar distributed between the two PM
      domains. Phosphatidylcholine was enriched in the apical membrane whereas
      sphingomyelin and glucosylceramide were enriched in the basolateral membrane. The
      possible function of this lipid polarity for the blood-brain barrier mechanism is
      the generation of a suitable lipid environment for polar distributed membrane
      proteins and the generation of two PM domains with different biophysical
      properties and permeabilities.

PMID- 11824474
TI  - Extracellular matrix-derived angiogenic factor(s) inhibit endothelial cell
      proliferation, enhance differentiation, and stimulate angiogenesis in vivo.
AB  - To isolate matrix molecules with angiogenic activity, tumor extracellular matrix
      (ECM) fractions from the basement membrane preparation Matrigel were analyzed for
      effects on endothelial cell (EC) proliferation, differentiation, and vessel
      formation in vivo. Inhibition of human and bovine EC DNA synthesis was evident
      upon treatment with several soluble Matrigel fractions including conditioned
      media (MGCM). After size fractionation of MGCM, EC growth arrest was activated by
      factor(s) smaller than 3,000 daltons (3KF). Bovine EC differentiation (tube
      formation) was promoted by both MGCM and 3KF fractions in two different models
      using matrigel or collagen gels to stimulate tube formation. The 3KF factor(s)
      stimulated angiogenesis when implanted in the cornea or subcutaneously in mice.
      FGF-induced angiogenesis and blood flow were increased in the presence of 3KF
      factor(s), an effect that was inhibited by the anti-angiogenic molecule
      endostatin. Further characterization of the low molecular weight 3KF samples by
      RP-HPLC revealed several fractions exhibiting EC growth arrest activity. These
      results suggest that the ability of ECM preparations to induce EC growth arrest
      and tube formation may reside, at least partially, in previously undetected low
      molecular weight molecules. Characterization of these ECM-associated inhibitors
      may lead to the development of novel anti-angiogenic and anti-tumor compounds.

PMID- 11824475
TI  - Influence of several methodological procedures utilized to obtain in vitro
      vascular preparations on endothelial activity.
AB  - Several maneuvers usually employed to set up isolated vascular preparations could
      effect the endothelium-dependent relaxation (EDR). The effects of five such
      maneuvers were studied in rings of rat aorta: 1) Type of anesthesia, 2) Cold
      storage of the vessels, 3) Length of the stabilization period, 4) Repeated
      contractions during stabilization, and 5) Performance of washouts during
      stabilization. Repeated contractions with norepinephrine (NE) 0.1 microM after
      stabilization altered neither the contraction nor the EDR induced by
      acetylcholine (Ach) 1 microM. Pentobarbital anesthesia and cold storage of the
      preparations for 24 h significantly decreased the EDR without effecting the
      contractile response of the rings. The absence of washouts during stabilization
      increased the contractions to either NE 0.1 microM or KCl 80 mM by nearly 50%.
      This increase was prevented by endothelial disruption or, in the presence of
      intact endothelium, by repeated washouts or by incubation with Bosentan 22
      microM. It is concluded that 1) Anesthesia of the animals and cold storage of the
      preparations can alter the EDR even in the absence of contractile changes in the
      smooth muscle, and 2) Accumulation of endothelin during the incubation period,
      even if not producing changes in the resting tension, can substantially alter the
      subsequent response to vasoactive interventions.

PMID- 11824476
TI  - Regulation of extracellular matrix remodeling and MMP-2 activation in cultured
      rat adrenal medullary endothelial cells.
AB  - We previously reported that short-term exposure of cultured rat adrenal medullary
      endothelial cells (RAMEC) to thrombin enhances the subendothelial deposition of
      extracellular matrix (ECM) proteins fibronectin, laminin, and collagen types I (C
      I) and IV (C-IV) (Papadimitriou et al. 1997). In this work, we extended our
      previous studies on factors that effect ECM protein deposition to include agents
      that activate or inhibit some of the most common intracellular signals such as
      cAMP, protein kinase C (PKC), and calcium. Furthermore, we investigated the
      possible link between the observed alterations in ECM protein deposition and the
      secretion of matrix metalloproteinase-2 (MMP-2). Forskolin (adenylyl cyclase
      activator) caused a dose-dependent increase in the deposition of all four ECM
      proteins studied. Isoproterenol beta-adrenergic receptor agonist) and the
      membrane permeant cAMP analogue dibutyryl-cAMP significantly increased the
      deposited amounts of ECM proteins at low concentrations, and this increase was
      reversed at higher concentrations of both agents. All these agents had the
      opposite effect on MMP-2 secretion, increasing it at doses where they decreased
      ECM protein deposition and vice versa. However, elevation of cAMP by the
      phosphodiesterase inhibitor IBMX had no effect either on the deposited amounts of
      any of the ECM proteins studied or on MMP-2 secretion. Activation of PKC by
      phorbol ester (PMA) resulted in a decrease in ECM protein deposition and an
      increase in MMP-2 secretion. Finally, chelation of intercellular calcium with
      BAPTA-AM resulted in an increased ECM deposition and a decrease in MMP-2
      secretion. Our results show a complex pattern of regulation of ECM protein
      deposition by cAMP-mobilizing agents and also indicate an inverse correlation
      between ECM protein deposition and secretion of MMP-2. The concerted regulation
      of both of these processes is essential in the formation of new blood vessels,
      and for the integrity of the vascular wall.

PMID- 11824477
TI  - TGF-beta1 induces an accumulation of connexin43 in a lysosomal compartment in
      endothelial cells.
AB  - We have been studying the relationships between cell growth and the expression of
      the gap junction protein Connexin43 (Cx43) in cultured bovine aortic endothelial
      cells (BAEC). As part of these studies, we examined the effect of the growth
      inhibitory cytokine TGF-beta1 on Cx43 expression. We have shown recently that TGF
      beta treatment increases Cx43 mRNA and synthesis, content, and half-life of the
      protein within 24 h, which leads, over the course of days, to an accumulation of
      Cx43 in large, intensely immunostaining vesicles, filling much of the perinuclear
      cytoplasmic space. In the current study, based on their distribution and markers,
      we identified these vesicles as lysosomes/autophagosomes. Cx43 immunostaining and
      staining with a fluorescent probe for acidic compartments are coincident, as
      retention of a fluorescent-labeled low-density lipoprotein occurs in a similar
      pattern and the same staining pattern can be detected in the treated cells using
      other markers for lysosomal compartments. TEM revealed prominent lysosomal
      figures with considerable heterogeneous material. After withdrawal of TGF-beta,
      the accumulated Cx43 was cleared only slowly, with some brightly immunoreactive
      cells remaining even after 72 h. The prolonged appearance (based on
      immunoreactivity in situ and in immunoblots) of intact vesicular Cx43 in the
      treated cells suggests decreased degradation, resulting from impaired lysosomal
      activity. These data not only emphasize the importance of the lysosome in
      connexin degradation, but also show that TGF-beta can cause an alteration in
      lysosomal functioning, with implications for cellular metabolism.

PMID- 11824478
TI  - Nitrobenzylthioinosine (NBT), a nucleoside transport inhibitor, protects against
      Shiga toxin cytotoxicity in human microvascular endothelial cells.
AB  - Infections with Shiga toxin (Stx)-producing Escherichia coli (STEC) cause
      microvascular endothelial cell damage, resulting in hemorrhagic colitis and
      hemolytic uremic syndrome. The prevention of endothelial cell damage is therefore
      a crucial step in overcoming this disorder. Here, we report that
      nitrobenzylthioinosine (NBT), a nucleoside transport inhibitor, has a protective
      effect against the cytotoxicity of Stxs in human microvascular endothelial cells
      (HMVECs). The relative viability of cells treated with 1.5-15 pM of Stx1 was
      reduced to 10-20% of that without Stx1. However, the viability of cells treated
      with NBT (10-100 microM) remained higher than 80%, even in the presence of Stx1.
      NBT also protected against Stx1 cytotoxicity in sodium butyrate-treated
      hypersensitive HMVECs. The protective effect of NBT against Stx cytotoxicity may
      be due to the depletion of ATP in the cells, thereby inhibiting the entry of
      Stx1.

PMID- 11824479
TI  - Insulin preincubation effects on rat vessel contractile responses: role of the
      endothelium.
AB  - The effect of contractions elicited with ET1 and AVP after preincubating rat
      aortic and tail artery rings with a hyperinsulinemic dose (3 nM) of insulin were
      studied. Insulin preincubation (120 min), in the presence of 0.1 mM L-NAME,
      depressed contraction of aortic rings to 0.01 microM ET1 (132 +/- 6 vs. 161 +/- 9
      mg/mm2 in control, n = 25; p < 0.05) and to 1 microM AVP (84 +/- 7 vs. 110 +/- 9
      mg/mm2 in control, n = 16; p < 0.05), but did not modify 45Ca influx to the cell.
      Insulin-induced relaxation was inhibited by indomethacin 10 microM, an antagonist
      of prostaglandin synthesis, and also by blockade of insulin receptors with 30
      microM genistein. A short insulin preincubation (15 min) did not modify ET1
      contractions. In rat tail artery, insulin preincubation (120 min) increased the
      force developed by ET1 (847 +/- 45 vs. 596 +/- 99 mgF/mgW in controls, n = 14) by
      stimulating TXA2 release and/or actions. In summary, the present results suggest
      that endothelial factors are involved in both the vasoconstrictor and vasodilator
      effects of insulin on rat vessels.

PMID- 11824480
TI  - Insulin preincubation effects on rat vessel contractile responses: role of the
      sarcoplasmic reticulum.
AB  - In the present work, we studied the possible mechanisms involved in the insulin
      induced acceleration of ET1 contractions. We observed a shortening of the half
      life needed to achieve maximal developed force (t(1/2)) at 10(-7) M ET1 in rat
      aortic rings preincubated for 120 min with 3 nM insulin (control 380 +/- 15 s vs.
      319 +/- 8 s with insulin, n = 28, p < 0.05). A tyrosine kinase linked receptor
      was involved in this effect because it was abolished by 30 microM genistein.
      Endothelium denudation and 10 microM indomethacin treatment did not effect this
      insulin effect, suggesting its independence of endothelial-derived factors. The
      effect was still present when the only source of Ca2+ was intracellular (t(1/2)
      values in the absence of external Ca2+: control 467 +/- 68 s vs. 213 +/- 28 s
      with insulin, n = 16, p < 0.05), but was blunted if the sarcoplasmic reticulum
      (SR) Ca2+ source was suppressed by exposure to 10 microM thapsigargin or 10
      microM ryanodine. Preincubation with insulin did not potentiate either SR 45Ca2+
      uptake or contractions evoked by caffeine-sensitive SR Ca2+ release. Since 30
      microM cheleritrine abolished insulin-induced acceleration of ET1 contractions,
      we propose that the hormone might enhance a signal pathway related to PKC in
      order to produce a faster Ca2+ release from the SR.

PMID- 11824481
TI  - Mechanotransduction of endothelial oxidative stress induced by cyclic strain.
AB  - Atherosclerotic lesions display a nonuniform distribution throughout the vascular
      tree. Mechanical forces produced by local alterations in blood flow may play an
      important role in the localization of atherosclerosis. One such force, cyclic
      strain, has been hypothesized to promote atherogenesis by inducing oxidative
      stress in endothelial cells, resulting in enhanced endothelial adhesiveness for
      monocytes. To investigate the signal transduction systems involved, human aortic
      endothelial cells were plated on flexible silicone strips that were either non
      coated or adsorbed with poly-L-lysine, vitronectin, fibronectin, or collagen I.
      Cells were then subjected to uniform sinusoidal stretch (10%) for 6 h.
      Endothelial superoxide anion production was increased in cells exposed to cyclic
      strain compared to static conditions. Furthermore, endothelial oxidative response
      to stretch was matrix protein-dependent, whereas cells grown on fibronectin and
      collagen I produced significantly more superoxide. The oxidative response to
      cyclic strain was reduced by coincubation with RGD peptides, blocking antibodies
      to alpha2- and beta-integrins antibodies, as well as inhibitors of protein kinase
      C. To investigate the effect of oxidative stress on gene transcription,
      endothelial cells grown on collagen I were transfected with an NFkappaB-sensitive
      luciferase construct. Cells that underwent cyclic strain displayed a tenfold
      induction of NFkappaB activation compared to static controls. Strain-induced
      luciferase activity was blunted by coincubation with RGD peptides or calphostin
      C. Thus, exposure of endothelial cells to cyclic strain led to integrin
      activation of a PKC-sensitive pathway that results in increased superoxide anion
      production and mobilization of NFkappaB.

PMID- 11824482
TI  - The prevention of schizophrenia: what interventions are safe and effective?
AB  - Obstetric complications appear to increase the risk of developing schizophrenia,
      and post-World War II improvements in obstetric care may have contributed to a
      decline in the incidence of the illness in the developed world. Educating
      providers and consumers of psychiatric and obstetric services about the risk of
      obstetric complications in increasing the risk of schizophrenia could bring about
      a further small decrease in the incidence of the illness, safely and at low cost.
      On the other hand, attempts to prevent the occurrence of schizophrenia by
      treating people who manifest high-risk indicators prior to the development of the
      illness have a low probability of success and a high probability of unintended
      negative consequences. Early intervention with people who have developed the full
      schizophrenia syndrome is likely to have few negative effects and may yield
      benefits, although it is not yet clear that it will.

PMID- 11824483
TI  - Pre-onset detection and intervention research in schizophrenia psychoses: current
      estimates of benefit and risk.
AB  - Early detection and intervention is offering a compelling new perspective on the
      diagnosis and treatment of schizophrenia spectrum disorders. Relevant
      investigations include efforts to reduce the post-onset duration of untreated
      psychosis and efforts to identify and treat prodromally symptomatic high-risk
      patients in the pre-onset phase of the disorder. There appears to be consensus
      that the benefits outweigh the risks in studies aiming to treat first episode
      psychotic patients as soon as possible. In contrast, there is less consensus
      about pre-onset detection and intervention studies, the major concerns being the
      false positive rate of case identification, the evidence of benefit, the side
      effects of treatment, the potential harm from being informed that one is at risk
      for psychosis, the false negative rate of case identification, and the inclusion
      of adolescents. In this article, each of these issues is elaborated upon and
      discussed in terms of the existing evidence informing risk and benefit and in
      light of our own clinical experience conducting this research. It is concluded
      that we do not have enough data yet to justify pre-onset detection and
      intervention as standard practice, but we do have enough data concerning risk and
      benefit to justify pre-onset detection and intervention research.

PMID- 11824484
TI  - Informed Consent in Early Psychosis Research: National Institute of Mental Health
      workshop, November 15, 2000.
AB  - Recent research on the early detection and treatment of schizophrenia has
      generated significant scientific interest along with considerable controversy and
      debate. Because our ability to alleviate fully the symptoms and deficits of
      established schizophrenia is limited, the prospect of interrupting disease
      progression early is compelling. At the same time, in the absence of an
      infallible marker of disease risk, there are serious questions about the safety,
      feasibility, and ethics of intervention research on "at-risk" or putatively
      prodromal individuals. A workshop, Informed Consent in Early Psychosis Research,
      was convened by the National Institute of Mental Health (NIMH) on November 15,
      2000, to review the results of recent research on early detection and
      intervention in schizophrenia. Beginning with the assumptions that (1) treatment
      of asymptomatic individuals with antipsychotic medication is not appropriate in
      research or clinical care, and (2) neither data nor clinical consensus defines
      optimal intervention for symptomatic at-risk individuals, workshop participants
      including clinical researchers, mental health consumers and family members,
      bioethicists, community health care providers, and NIMH staff-systematically
      reviewed available data on the potential risks and benefits of alternate
      approaches to the management of prodromal states. Ethical issues involved in
      early detection and intervention studies were discussed. Workshop participants
      summarized information presented during the meeting into informed consent
      "bullets" that must be communicated to, and understood and appreciated by,
      potential research participants.

PMID- 11824485
TI  - A prospective study of factors influencing adherence to a continuous neuroleptic
      treatment program in schizophrenia patients during 2 years.
AB  - Dropout from prophylactic neuroleptic treatment is one major reason for relapse
      in schizophrenia patients. There is a lack of prospective studies on factors that
      predict medication adherence. We investigated factors suspected to predict
      dropout from continuous neuroleptic treatment in a 2-year prospective study
      involving 122 outpatients with a DSM-III-R diagnosis of schizophrenia. Forty-two
      (34.4%) were classified as patient-related dropouts. No significant difference
      between compliant patients and dropouts was found with regard to sociodemographic
      variables, except that compliant patients were significantly older. Also, no
      differences in psychopathology were seen at the beginning of treatment, but
      compliant patients had a longer duration of illness. Compliant patients had
      higher doses of neuroleptics in the initial stabilization phase and
      correspondingly showed more extrapyramidal signs. Physicians rated compliant
      patients from the beginning as more cooperative. These patients also showed
      significantly higher scores in positive treatment expectations. In a stepwise
      regression analysis, positive illness concepts, the global assessment of
      functioning (GAF), and the physicians' view of patients' cooperation predicted 19
      percent of the variance. We concluded that the prediction of dropouts is
      insufficient and remains largely an unsolved problem. Future research should
      focus more on context factors in the search for clinically meaningful
      explanations of patient dropout from treatment.

PMID- 11824486
TI  - Short report: comparison of patient satisfaction and burden of adverse effects
      with novel and conventional neuroleptics: a naturalistic study.
AB  - Converging evidence indicates that, in controlled drug trials, individuals
      receiving novel antipsychotic medications have fewer adverse effects than those
      receiving conventional antipsychotic medications. This in turn may lead to
      greater patient treatment satisfaction. This study examines patient satisfaction
      and burden of adverse effects in a county-wide epidemiologic study of first
      admission psychotic persons with psychosis who were receiving novel antipsychotic
      drugs (n = 42). Comparisons were made within this group, and between 25 of these
      persons and 25 others with the same diagnosis and sex, from the same
      epidemiologic study, who were receiving a comparable regimen of conventional
      antipsychotic drugs. Patients receiving novel antipsychotics were significantly
      more satisfied and were significantly less burdened by adverse effects than those
      receiving conventional antipsychotics. Among the group receiving novel
      antipsychotics, dosage was not related to satisfaction or burden of adverse
      effects. For those treated with risperidone (n = 27), there was a difference,
      approaching statistical significance, for greater satisfaction and less adverse
      effect burden among those persons with dosages less than 5 mg daily as compared
      to higher dosages.

PMID- 11824487
TI  - Tardive dyskinesia--diagnostic issues, subsyndromes, and concurrent movement
      disorders: a study of state hospital inpatients referred to a movement disorder
      consultation service.
AB  - Of 49 state hospital patients referred for movement disorder consultation for
      tardive dyskinesia (TD), 11 (23.9%) of 46 meeting inclusion criteria had movement
      disorders other than TD. These other disorders led to a false diagnosis of TD in
      6 subjects (12.2%). Between-day dyskinesia variability affected TD ascertainment
      in only 3.2 percent of subjects. Prevalences of other neurological conditions in
      the 30 patients identified with definite TD were parkinsonism (90%), dystonia
      (25%), akathisia (16%), cerebellar signs (40%), dysmetria (23%), cerebellar
      tremor (17%), tardive dystonia (3.3%), and tardive akathisia (3.3%). Concurrence
      rates of parkinsonism with TD varied significantly according to which clinical
      signs were used to define parkinsonism. Using a rating score threshold of at
      least mild, rigidity occurred in 79.3 percent, bradykinesia in 55.2 percent, and
      resting tremor in 41.4 percent of subjects with TD; more significant rigidity
      occurred in 41.4 percent, bradykinesia in 31.0 percent, and resting tremor in
      20.7 percent. Concurrence rates of neurological conditions with TD subsyndromes
      were distributed rather evenly according to condition prevalences, except for an
      association of cervicotruncal TD with bradykinesia (perhaps because of
      ventromedial striatal presynaptic and postsynaptic D2 blockade, respectively).
      These findings, as well as the occurrence of equal gender ratio and relative
      under-representation of bipolar and alcohol disorders in subjects with definite
      TD, are discussed.

PMID- 11824488
TI  - When symptoms persist: clozapine augmentation strategies.
AB  - Recent data and clinical experience confirm that, in spite of superior efficacy
      for treatment-refractory schizophrenia, a substantial proportion of patients
      receiving clozapine will continue to experience disabling symptoms. Optimizing
      clozapine monotherapy is the first step in the management of "clozapine
      nonresponders." Described here is a synthesis of the available literature on the
      range and efficacy of clozapine augmentation strategies that may be used when
      monotherapy fails. Treatment options include adjunctive antipsychotic
      medications, mood stabilizers, selective serotonin reuptake inhibitors,
      glycinergic agents, and electroconvulsive therapy. The evidence favoring one
      augmentation strategy over another is lacking; overall, adjunctive therapy is
      associated with only modest clinical improvement. Moreover, case series and open
      labeled clinical trials dominate the extant literature, and there is a dearth of
      double-blind trials comparing these augmentation agents. Current systematic
      efforts to enhance the treatment of these patients with adjunctive therapies are
      worthy of being studied in carefully conducted clinical trials.

PMID- 11824489
TI  - Neurodevelopmental origins of tardivelike dyskinesia in schizophrenia patients
      and their siblings.
AB  - The question of whether dyskinesia of the type found in tardive dyskinesia (TD)
      related to schizophrenia has a neurodevelopmental background was studied in a
      sample of 60 younger schizophrenia patients (mean age 38 years) and 21 of their
      non-ill siblings. TD-like dyskinesia was studied in relation to selected risk
      factors in the patients, and to neurological abnormality and parkinsonism in both
      patients and siblings. One or more signs of TD-like dyskinesia in patients were
      predicted by male gender, a history of obstetric complications, shorter illness
      duration, and shorter neuroleptic exposure. One or more signs of TD-like
      dyskinesia were found in 28.5 percent of the siblings and tended to be associated
      with neurological abnormality. Little co-occurrence of TD-like dyskinesia was
      found in the sibling and the patient in the same family. Patients' TD-like
      dyskinesia was significantly associated with hard neurological signs (independent
      of involuntary movements) but not with soft signs or primitive reflexes per se.
      TD-like dyskinesia showed a significant positive relationship to parkinsonism in
      patients. TD-like dyskinesia in younger schizophrenia patients appears to have
      neurodevelopmental antecedents and seems to represent one aspect of the total
      neurological abnormality associated with schizophrenia.

PMID- 11824490
TI  - Contingency valuation and preferences of health states associated with side
      effects of antipsychotic medications in schizophrenia.
AB  - The purpose of this study was to investigate the construct validity and the test
      retest reliability of the willingness to pay (WTP) method for estimating health
      state preferences associated with side effects of antipsychotic medication.
      Ninety-six schizophrenia patients on antipsychotics were asked (1) how much they
      would be willing to pay to get rid of side effects with 100 percent probability,
      (2) a standard gamble (SG) question measuring utilities of patient's health state
      associated with side effects, and (3) their WTP to get rid of side effects based
      on the utility found with SG. Patients were divided into three groups based on
      severity of side effects. There was a significant difference between side effect
      severity groups for (1) the utility associated with side effects (Kruskal-Wallis
      [K-W] chi-square = 8.48, p = 0.014), and (2) their WTP to get rid of side effects
      with either 100 percent probability (K-W chi-square = 14.32,p = 0.001) or based
      on the utility associated with side effects (K-W chi-square = 5.96, p = 0.051).
      There was a significant correlation between utility and the WTP based on utility
      (Spearman r = -0.42, p = 0.003). Because of a wide variation in side effects at
      the 1-month interval, we were unable to assess the test-retest reliability of SG
      and WTP. Our results suggest that WTP has some construct validity in valuating
      and measuring preferences of health states associated with side effects of
      antipsychotics in schizophrenia.

PMID- 11824491
TI  - Predicting the costs of community care for individuals with severe mental illness
      in South London.
AB  - The objective of this study is to identify factors that predict the costs of
      community mental health services. A random sample of individuals, selected from
      all identified cases of psychosis in two geographically defined catchment areas,
      were interviewed before the establishment of community mental health teams and
      then after these teams had been operating for approximately 2.5 years. One of the
      sectors developed an intensive community service, with a more standard service in
      the other sector. Significant predictors of higher costs were older age and
      higher levels of disability. Predictors of lower costs were longer duration of
      illness and more years of education. A reduced model revealed that being male and
      having more symptoms were also predictors of higher costs. After controlling for
      background characteristics, it was revealed that services provided to clients
      from the intensive sector were $1,894 more expensive over 6 months than those
      provided to standard sector clients.

PMID- 11824492
TI  - Two strategies for family intervention in schizophrenia: a randomized trial in a
      Mediterranean environment.
AB  - Controlled intervention studies carried out in families of schizophrenia patients
      have been shown to have a positive impact in relapse prevention, but it remains
      to be seen whether different forms of family intervention affect outcomes other
      than relapse and hospital readmission in different ways. This study compared the
      outcome profile of relevant clinical variables after two different family
      intervention strategies for schizophrenia patients in public health care in a
      Spanish sample. We conducted a randomized controlled study comparing (1) a
      relatives group (RG) and (2) a single-family behavioral family therapy (BFT),
      both offered as standard treatment in one catchment area in Valencia. All
      randomized patients were included in the main analysis, and all cases remained in
      the therapy group to which they were originally assigned regardless of whether
      they suffered a relapse. The relapse rate at 12 months for the 87 cases studied
      was not significantly different in the two groups, but the two approaches did
      affect outcomes other than relapse and rehospitalization (such as social
      functioning, dose of antipsychotic medication, "delusions" and "thought
      disorder") in different ways. The BFT approach offered more advantages than the
      RG approach. The results suggest that these approaches should always be
      implemented in a clinical environment in a Mediterranean setting.

PMID- 11824493
TI  - Interpersonal control and expressed emotion in families of persons with
      schizophrenia: change over time.
AB  - This study examined communication patterns in 62 families of persons with
      schizophrenia, comparing families with relatives who were low expressed emotion
      (EE) at the beginning and end of a 2-year study, those who were high EE at the
      beginning and end, and those whose EE status changed. Interaction was coded with
      the Relational Control Coding System and analyzed as a Markov process. Dialogues
      in the stable low-EE and stable high-EE families were rather similar initially,
      and both groups showed increasing flexibility at year 1. However, at year 2, low
      EE dyads showed increasingly complex structure and flexibility in control, but
      high-EE dyads showed simpler structure and rigidly controlling patterns. When EE
      status changed, so did the structure of the dialogues and the patterning of
      control. Although earlier research found more "tightly joined" systems in
      families of high-EE relatives, it may be that over time, these family members
      distance from each other and so are less connected. It is also possible that
      relatives who remain high EE despite intervention are a subset of high-EE
      relatives who need more support or different therapeutic approaches to maintain
      change.

PMID- 11824494
TI  - Attentional characteristics of schizophrenia patients differing in learning
      proficiency on the Wisconsin Card Sorting Test.
AB  - The Wisconsin Card Sorting Test (WCST), a test of concept formation, was given to
      49 schizophrenia inpatients in three blocks of 64 cards each with the second
      block comprising special instructions and trial-by-trial feedback. With the help
      of a psychometric algorithm based on linear regression analysis, the patients
      were classified according to their response to these specific interventions.
      Results yielded 15 high scorers, 23 learners, and 11 nonlearners. This a priori
      classification was confirmed by cluster analysis. Next, these groups were further
      analyzed with the Degraded Stimulus Continuous Performance Test (DS-CPT), a test
      of target discrimination, and the Test of Attentional Style (TAS), which assesses
      habitual, subjectively experienced attentional problems. A significant difference
      between high scorers and nonlearners was found for discriminative sensitivity
      (d'), with the learners achieving intermediate scores. Results for only the DS
      CPT response criterion (beta) and a TAS subscale (Distractibility) tended to be
      significant. Discriminant analysis also revealed that d' is the most powerful
      variable for discriminating among the subgroups. The article also addresses
      baseline versus dynamic assessment, specific rehabilitation needs in subgroups of
      schizophrenia patients different in learner status, and the neurocognitive
      characteristics of the subgroups.

PMID- 11824496
TI  - Evidence of schizophrenia patients' reduced perceptual biases in response to
      emotion chimera.
AB  - The goal of the study was to determine whether dextral individuals with
      schizophrenia display atypical perceptual biases in response to faces in general,
      or whether they display atypical perceptual biases in response to emotional
      facial cues. To this end, we assessed perceptual processing in schizophrenia
      patients with four types of free-vision chimeric stimuli. Perceptual biases were
      evaluated in 45 schizophrenia patients and in 46 controls using two face
      (emotion, gender) tasks and two nonface (dots, gradients) tasks. In response to
      the emotion chimera, the patients with schizophrenia displayed a reduced left
      perceptual bias. The two groups did not differ significantly in their response to
      the gender chimera or to the two nonface chimera. These findings are consistent
      with the assertion that schizophrenia patients have impaired emotional
      perception. In the discussion we consider possible reasons for schizophrenia
      patients' difficulty comprehending emotional facial stimuli. We suggest that
      schizophrenia patients' reduced perceptual bias in response to the emotion
      chimera reflects a hypothesized affective information-processing deficit.

PMID- 11824495
TI  - Neuropsychological functioning as a moderator of the relationship between
      psychosocial functioning and the subjective experience of self and life in
      schizophrenia.
AB  - Psychosocial interventions and models of quality of life in schizophrenia are
      based on the notion that increases in psychosocial functioning will be related to
      improvements in subjective experience outcomes such as self-esteem and
      satisfaction with life. However, studies have repeatedly failed to demonstrate a
      direct relationship between psychosocial functioning and subjective experience in
      schizophrenia. This study of 40 individuals diagnosed with schizophrenia examined
      whether neurocognitive measures of executive functioning moderated the
      relationship between psychosocial functioning and subjective experience.
      Subjective experience was represented by measures of satisfaction with life and
      self-esteem. The Global Assessment Scale measured psychosocial functioning, and
      the Wisconsin Card Sorting Test measured executive functioning. Multiple
      regression and correlation analyses indicated that executive functioning was a
      strong moderator. Specifically, individuals with schizophrenia with impaired
      executive functioning displayed a positive and statistically significant
      association between psychosocial functioning and both measures of subjective
      experience (r = 0.55 and 0.61). However, among schizophrenia patients with intact
      executive performance, psychosocial functioning was negatively associated with
      self-esteem and satisfaction with life (r = -0.24 and -0.46). And the findings
      were internally replicated using two other neuropsychological measures relevant
      to executive functioning. These findings indicate that executive functioning
      plays a major role in moderating the relationship between subjective experience
      and psychosocial functioning in schizophrenia. Implications for biosocial models,
      psychosocial interventions, and models of quality of life in schizophrenia are
      discussed.

PMID- 11824497
TI  - First Person Account: landing a Mars lander.
AB  - The article that follows is part of the Schizophrenia Bulletin's ongoing First
      Person Account series. We hope that mental health professionals--the Bulletin's
      primary audience--will take this opportunity to learn about the issues and
      difficulties confronted by consumers of mental health care. In addition, we hope
      that these accounts will give patients and families a better sense of not being
      alone in confronting the problems that can be anticipated by persons with serious
      emotional difficulties. We welcome other contributions from patients, ex
      patients, or family members. Our major editorial requirement is that such
      contributions be clearly written and organized, and that a novel or unique aspect
      of schizophrenia be described, with special emphasis on points that will be
      important for professionals. Clinicians who see articulate patients with
      experiences they believe should be shared might encourage these patients to
      submit their articles to Schizophrenia Bulletin, First Person Accounts, EEI
      Communications, 66 Canal Center Plaza, Suite 200, Alexandria, VA 22314.--The
      Editors.

PMID- 11824498
TI  - A voice accumulator device: evaluation based on studio and field recordings.
AB  - A voice accumulator is a portable device for long-term measurements of voice use
      in natural conditions. A contact microphone attached to the front part of the
      neck registers vocal fold vibrations. The purposes of the present study were: 1)
      to evaluate the voice accumulator's two measuring programs optimized for
      registration of fundamental frequency (F0) and phonation time, respectively; and
      2) to test the voice accumulator for field recordings. Four healthy subjects were
      recorded in a sound-proof booth simultaneously with one contact microphone into a
      voice accumulator and one contact microphone into a computer. In terms of F0 and
      phonation time, the results showed that correlations between the voice
      accumulator's two measuring programs and a signal-processing program were high (r
      > or = 0.85) for all subjects but one. The inter-subject variability was large. A
      prerequisite for reliable vocal fold vibration detection by the voice accumulator
      was a careful placement and a firm attachment of the contact microphone on the
      neck. Four subjects were recorded with the voice accumulator during a working
      day. It was concluded that the voice accumulator is an overall good instrument
      for measurements of F0 and phonation time, and thus is useful for both clinical
      work and research.

PMID- 11824499
TI  - Effects of sound amplification on teachers' speech while teaching.
AB  - Voice problems are common among teachers. This is most likely due to the heavy
      vocal load of their profession. The present study investigated one possible
      method to decrease the vocal load. The effects of amplification on classroom
      speech were studied on five Icelandic teachers (three females, two males, mean
      age 51 years). Classroom speech was recorded with a portable DAT recorder and a
      head-mounted microphone, first under ordinary conditions and in the next week
      while using electrical sound amplification. The average fundamental frequency
      (F0), sound pressure level (SPL) and phonation time were measured. According to
      the results, amplification significantly lowered both F0 (average 8.6 Hz for the
      females and 11.3 Hz for the males, p = 0.002 and 0.0001, respectively) and SPL
      (about 1 dB for both genders, p < 0.05), while phonation time was not
      significantly affected. The results suggest that electric amplification is likely
      to reduce vocal load.

PMID- 11824500
TI  - The effect of MPEG audio compression on multidimensional set of voice parameters.
AB  - The MPEG-1 Layer 3 compression schema of audio signal, or commonly known as mp3,
      has caused a great impact in recent years as it has reached high compression
      rates while also conserving a high sound quality. Previous listening tests have
      shown that music and speech samples compressed at high bitrates are virtually
      indistinguishable from the original samples, but very little is known about how
      compression acoustically affects the voice signal. In Experiment 1 the spectral
      composition of original and compressed speech signals were analyzed by means of
      the Long-Term Average Spectrum using the Computerized Speech Laboratory (Kay
      Elemetrics Corp. (Pine Brook, NJ, USA)). In Experiment 2 a set of 29 voice
      parameters extracted by using the Multidimensional Voice Program of Kay are
      compared between original and compressed voices at different bitrates. Results
      show a high fidelity at high-bitrate compressions (128 and 160 kbit per second
      (kbps)) both in voice parameters and the amplitude-frequency spectrum.
      Compressions at 64 kbps or lower bitrates introduces substantial modifications in
      the voice signal, seriously altering parameters related with tremor, amplitude
      perturbation, noise, subharmonics and voice irregularities, likewise the signal
      spectrum is altered in its high frequency region.

PMID- 11824501
TI  - Long-term average spectrum (LTAS) analysis of sex- and gender-related differences
      in children's voices.
AB  - Long-term average spectrum (LTAS) analysis offers representative information on
      voice timbre providing spectral information averaged over time. It is
      particularly useful when persistent spectral features are under investigation.
      The aim of this study was to compare perceived sex of children to the LTAS
      analysis of their audio signals. A total of 320 children, aged between 3 and 12
      years, were recorded singing a song. In an earlier analysis, the recorded voices
      were evaluated with respect to perceived and actual sex by experienced listeners.
      From this group, a subgroup of 59 children (30 boys and 29 girls) was selected.
      The mean LTAS revealed a peak at 5 kHz for children perceived with confidence as
      boys, and a flat spectrum at 5 kHz for children perceived confidently as girls
      (whether male or female in actuality).

PMID- 11824502
TI  - Limited brain access for leptin in obesity.
AB  - Obesity is a major health problem that contributes to the development of type 2
      diabetes, hypertension, dyslipidemia, and cardiovascular disease. The current
      pharmacological therapies for obesity are limited and may have significant side
      effects. Leptin therapy was shown to effectively cause weight loss in obese rats,
      however its effectiveness in humans is still under investigation. Obese humans
      have significantly elevated plasma leptin concentrations compared with lean
      individuals. Plasma leptin concentrations strongly correlated with percentage of
      body fat. Leptin concentration in the cerebrospinal fluid (CSF) is correlated, in
      a nonlinear manner, with plasma leptin levels and body mass index (BMI). The
      ratio of CSF leptin levels to serum leptin levels was 4 times greater in lean
      individuals than in obese individuals. One interpretation of this finding is that
      human obesity could be secondary to a central resistance to leptin action,
      causing a relative leptin deficiency in the CNS. Six years after the discovery of
      leptin we still do not have a clear understanding of how leptin accesses its
      targets in the brain, or whether there is defect in this process in the brain of
      obese individuals. In this manuscript we will review the different leptin
      gateways to the brain and the potential sites where a defect in leptin action may
      be present, as well as some potential clinical implications of leptin. A better
      understanding of how leptin reaches the brain and how it modulates the release of
      hypothalamic neuropeptides will be important in understanding the role that
      leptin plays in the pathophysiology of obesity.

PMID- 11824503
TI  - Influence of cortisol status on leptin secretion.
AB  - The discovery of the adipocyte-produced hormone leptin has changed the field of
      obesity research and our understanding of energy homeostasis. It is now accepted
      that leptin is the afferent loop informing the hypothalamus about the states of
      fat stores, with hypothalamic efferents regulating appetite and energy
      expenditure. I addition, leptin has a role as a metabolic adaptator in overweight
      and fasting states. New and previously unsuspected neuroendocrine roles have
      emerged for leptin. Leptin participates in the expression of CRH in the
      hypothalamus, interacts at the adrenal level with ACTH, and is regulated by
      glucocorticoids. Since leptin and cortisol show an inverse circadian rhythm, it
      has suggested that a regulatory feedback is present. However glucocorticoids
      appears to play a modulatory, but not essential roles in generating leptin
      diurnal rhythm. Glucocortiocids act directly on the adipose tissue and increase
      leptin synthesis and secretion in humans. Leptin levels are markedly increased in
      Cushing's syndrome patients and in other pseudo-Cushing's syndrome states.
      Glucocorticoids appears to act as a key modulator of body weight and food intake,
      promoting leptin secretion by adipocytes, limiting central leptin induced effects
      and favoring those of the NPY. Furthermore the modulatory role of glucocorticoids
      could be altered in obesity, but the precise mode of action remains to be
      established. The relevance of this finding merits further studies.

PMID- 11824504
TI  - Leptin and the pituitary.
AB  - In 1994, Zhang et al. of Rockefeller University in New York reported the first
      successful complementary DNA (cDNA) cloning of leptin by the positional cloning
      method. Leptin was identified as the gene of ob/ob mouse in genetic obesity
      syndromes. It has very strong food intake control, and body weight and energy
      expenditure. The name "leptin" derived from the Greek word leptos, meaning
      "thin." We hereby review major advances leading to our current finding of leptin,
      leptin receptor and its structure, the outline of homozygote, and also influence
      of leptin in the pituitary. (The structure of leptin) The mouse obese gene has
      been localized to chromosome 6. With human leptin gene on chromosome 7q31.3, its
      DNA has more than 15000 base pairs and consists of three exons and two introns.
      For bioactivation of leptin the importance of disulfide-binding site is
      suggested. Human leptin which replaced the 128-th arginine with glutamine has the
      function of an aldosteron antagonist, which is reported to have the function of
      athrocytosis inhibition. The resemblance of leptin precursor of human, mouse and
      rat is very high, i.e., mouse and rat homology is 96% and mouse and human
      homology is 83%. (The structure of leptin receptor) The mutant gene, which is the
      cause of obesity, was shown on map on diabetic mouse (db/db) chromosome 4, and it
      was proven to be the same as the leptin receptor gene cloned by Tartaglia et all.
      Further studies have found the Zucker fatty rat (fa/fa) to be incorporated into a
      linkage map of rat chromosome 5, whose region of rat is the equivalent to the
      region of conserved synteny of the db/db mouse gene. The leptin receptor is
      glycoprotein consisting of a single transmembrane-spanning component. The primary
      structure of leptin receptor belongs to the cytokine-class1 family, the single
      membrane-spanning receptor, and is highly related to the gp130 signal-transducing
      component of the interleukin-6 (IL-6) receptor, the granulocyte colony
      stimulating factor (G-CSF) receptor, and the leukemia inhibitory factor (LIF)
      receptor. The leptin receptor is known to have at least six existing isoforms (Ob
      Ra, b, c, d, e, f) from the difference in splicing. (Homozygote Mutation of
      Leptin and Leptin Receptor :Hormone Secretion Disorders) The point mutation of
      ob/ob mouse and the splicing mutation of db/db mouse show remarkable obesity and
      hyperphagia. These obesity models show a reproduction disorder with both the male
      and the female, and they develop with homozygote. The cause is thought to be the
      gonadotropin secretory abnormality in pituitary. Three family lines report the
      cases of this deficiency, and it is considered that the secretory abnormality in
      pituitary develops into hypogonadotropic. These patients show low value in plasma
      FSHbeta (follicle stimulating hormone-beta and LHbeta (luteinizing hormone-beta
      which are produced from pituitary, and the plasma GnRH (gonadotropin releasing
      hormone) level is also low. Furthermore, the leptin receptor deficient family
      line was reported in 1998, in which case only the homozygote developed. The
      plasma leptin concentration of normal human is about 8.0 ng/ml, and this case
      with leptin receptor deficiency has high value of 500-700 ng/ml, which is the
      equivalent to the db/db mouse. (Role of Leptin in Hypothalamus-Pituitary
      Periphery Function) The role of leptin which regulates pituitary hormones
      suggests the promotion the GHRH (growth hormone releasing hormone) secretion in
      hypothalamus-pituitary axis, with the possibility of the rise in secretion of GH
      (growth hormone) in pituitary, i.e. effects of icv (intracerebroventricular)
      infusion of leptin has spontaneously stimulated GHRH, which promotes GH secretion
      in the normal rats. On the other hand, topical treatment of GH3 (derived from a
      rat pituitary GH-secreting cell line) with leptin directly inhibits cell
      proliferation. The obesity model animals (ob/ob, db/db, fa/fa) have equally plump
      body compared to the normal models, which shows signs of sufficient growth.
      (Localization and Functional Relevance of Leptin and Leptin Receptor in Rodents
      Pituitary) Aside from being the food intake inhibitor and the energy control
      factor, leptin takes part in controlling the pituitary hormones. Promoting the
      secretion of GH, PRL (prolactin), TSHbeta (thyroid stimulating hormone-beta,
      FSHbeta/LHbeta, and inhibiting the secretion of ACTH (adrenocorticotropic
      hormone) are the major changes of pituitary hormones which are brought on by
      leptin. The expressive localization is specific, and immunohistochemistry (IHC)
      method recognized leptin in granular state in FSHbeta, LHbeta and TSHbeta
      positive cells. In our biochemical examination, the bulk of the expression of
      leptin is recognized in fraction of the secretory granule. In particular, FSHbeta
      cells had the highest percentage rate of colocalized leptin in rat pituitary. On
      the other hand, leptin receptor has been reported to be found only in normal rat
      pituitary, human pituitary adenoma, and respective cell lines in pituitaries by
      the RT-PCR method until now, but we disclosed for the first time the localization
      of leptin receptor on the plasma membrane of GH-secreting cells with the IHC
      method that has not been cleared so far. These findings show that leptin and
      leptin receptor have been expressed in different cells, and that the rat
      pituitary glands entertain paracrine mechanism between leptin (FSHbeta/LHbeta
      cells) and leptin receptor (GH cells). The function of paracrine in this
      pituitary suggests a new point of view in hypothalamus-pituitary axis, and it
      shall be concerned with many aspects such as hormone secretions and
      proliferation/inhibition. (Human Pituitary Adenoma) Preliminary report of leptin
      and leptin-receptor relationship with pituitary adenoma that has secretion
      abnormality has been filed, and its manifestation is being observed by the RT
      PCR. Leptin and leptin receptor are expressed in most adenoma, and it is thought
      to function by autocrine and paracrine pathway in the adenomas. Leptin has been
      located in ACTH-secreting adenoma most frequently, especially in ACTH carcinoma.
      The leptin receptor is detected in all adenomas with high percentage rate, with
      both long and short forms, and then many cases of nonfunctioning pituitary
      adenomas, compared with other adenomas, have been reported to be positive with
      both long and short forms of leptin receptor as detected by RT-PCR. The HP75 cell
      line is derived from the nonfunctioning pituitary adenoma, which produces FSHbeta
      and LHbeta. The expression of leptin receptor in nonfunctioning pituitary
      adenoma, and the suppression of HP75 multiplication may lead to the possible
      hypothesis of leptin becoming one factor for the treatment of pituitary adenoma,
      especially in gonadotropin adenomas.

PMID- 11824505
TI  - Neuroendocrine effects of leptin.
AB  - Leptin, the product of the obesity gene, is a cytokine-like circulating protein
      acting as a peripheral satiety signal to the hypothalamus. It was initially
      described as a secreted product of white adipose cells, but more recent data have
      demonstrated its expression by endocrine and neuroendocrine tissues like the
      ovary and the hypothalamus, as well as several anterior pituitary cell types. The
      effects of leptin on body weight homeostasis are mediated via different
      hypothalamic neurotransmitters regulating appetite and energy expenditure. In
      addition, leptin participates to the modulation of the activity of the
      neuroendocrine thyrotrope, somatotrope, corticotrope and gonadotrope axes. These
      endocrine effects of leptin have progressively emerged as important physiological
      functions of this molecule. Its role as a permissive factor for puberty and
      normal reproductive function in adulthood is becoming widely recognized. In
      addition, leptin participates in the fine tuning of the corticotrope axis. Thus,
      by signalling body fat stores to the hypothalamus and other endocrine organs,
      leptin serves as a metabolic integrator of several neuroendocrine functions. The
      precise site of action and mode of regulation of the gonadotrope and somatotrope
      axes by leptin are reviewed.

PMID- 11824507
TI  - Leptin in pituitary adenomas--a novel paracrine regulatory system.
AB  - A growing number of physiological and pathophysiological processes have been
      shown to be influenced by leptin apart from its first recognised role as a
      modulator of hypothalamic appetite and weight control centers. We investigated
      the presence and pattern of distribution of leptin mRNA and the mRNA of the long
      isoform of the leptin receptor in the normal pituitary and in different types of
      pituitary adenomas. We also studied leptin secretion from human pituitary tumors
      in culture, and the in vitro pituitary hormone release following stimulation with
      human leptin. Leptin mRNA expression was detected at a low level of expression in
      50% of tumors but in none of the normal pituitaries. By immunohistochemistry,
      leptin was present in occasional scattered cells in the normal pituitary and in
      pituitary tumors. The leptin receptor long isoform was detected in the majority
      (65%) of pituitary tumors and in all normal pituitaries. It did not segregate
      with any particular tumor type, and varying levels of expression were detected
      between the tissues studied. 34% of pituitary adenomas showed leptin release into
      the incubation media during in vitro culture. Leptin mRNA, the mRNA of the long
      isoform of the receptor, or in vitro leptin release, did not correlate with tumor
      type or with any of the other pituitary hormones released. In vitro leptin
      stimulation of pituitary tumors caused stimulation of FSH and a-subunit secretion
      from a non-functioning adenoma and TSH secretion from a somatotroph adenoma. As
      the co-localisation of ACTH and leptin in corticotroph cells was previously
      suggested, we investigated whether in vivo ACTH release is accompanied by a
      simultaneous plasma leptin level rise (i) in peripheral plasma samples after food
      intake-induced ACTH rise in healthy obese and nonobese individuals and (ii) in
      petrosal sinus samples after CRH injection in Cushing's disease patients. Our
      data suggest that a rise in ACTH levels is not accompanied by detectable rise in
      leptin levels in peripheral and in petrosal sinus blood samples. In summary,
      leptin is synthesized and stored within the pituitary and may modulate other
      pituitary hormone secretion, although probably it does not contribute to plasma
      leptin level changes. Pituitary leptin may therefore be a novel paracrine
      regulator of pituitary function.

PMID- 11824508
TI  - Anterior pituitary corticotropes of adrenalectomized, leptin-administered rats.
AB  - Leptin (LEP), the product of the ob gene is an adipose-tissue secreted hormone
      that acts to decrease caloric intake and increase energy expenditure. Some
      observations suggest the mutual relationship between leptin and blood ACTH
      levels. In the rat acute LEP administration enhances blood ACTH levels while
      prolonged treatment lowers blood corticotropin concentrations. Since the
      pituitary-derived ACTH is an important element in functioning of that loop,
      studies were undertaken to investigate the effect of prolonged LEP administration
      on anterior pituitary ACTH cells of adrenalectomized rats. Studies were performed
      on bilaterally adrenalectomized adult female rats. They were administered for 3
      or 6 days with 2.7 nmol/rat/day LEP (recombinant human leptin) or with the
      vehicle (0.9% NaCl). LEP administration did not affect the body weight of
      bilaterally adrenalectomized rats. During the whole experiment the average
      increase in body weight was 3.9-4.3 g/day. LEP administration into
      adrenalectomized rats had no effect on anterior pituitary weight. This treatment
      resulted in a significant increase in pituitary ACTH concentration and content,
      and these changes were accompanied by a potent decrease in blood corticotropin
      level. LEP administration into adrenalectomized rats only insignificantly lowered
      the quantity of anterior pituitary ACTH-immunoreactive cells and their average
      area. On the opposite, the average volume of pituitary corticotropes of LEP
      treated rats was notably lower than that in adrenalectomized-vehicle administered
      ones. Results of performed experiments clearly demonstrate that prolonged LEP
      administration results in a notable inhibition of the growth and secretory
      activity of anterior pituitary corticotropes of the adrenalectomized rats.

PMID- 11824509
TI  - Pituitary leptin gene expression is reduced by neonatal androgenization of female
      rats.
AB  - We have previously reported evidence of leptin gene expression (ob mRNA) in adult
      rat brain and pituitary gland. We have also shown that ob mRNA levels in female
      rat brain and pituitary are regulated in an age- and tissue-dependent fashion. In
      view of the known sexual dimorphism in adipose tissue leptin expression, we have
      extended our original work to include an assessment of ob mRNA levels in brain,
      pituitary and fat of developing male and female rats. In addition we determined
      the effects of neonatal androgenization of female rat pups with testosterone
      propionate. Leptin (ob) mRNA expression was evaluated using semi-quantitative RT
      PCR analysis. Leptin mRNA levels were developmentally regulated in the pituitary
      and cortex of male rats, paralleling the changes previously observed in female
      rats. In the pituitary, leptin expression was significantly higher during the
      early postnatal period and dropped abruptly by postnatal day (PD) 22. In the
      cortex, leptin expression was lowest at PD 4 and rose significantly by PD 14. In
      addition gender differences, most notably in the pituitary, were also observed.
      In pituitary gland, ob mRNA was significantly higher in female rats than in males
      at PD 14 (+60%; p < 0.05) but there were no sex differences at PD 4 and PD 22.
      Testosterone treatment of neonatal female rats profoundly reduced ob mRNA at PD
      14 (3.5-fold; p < 0.01) and PD 22 (3-fold; p = 0.05). In subcutaneous adipose
      tissue and hypothalamus we observed no sex difference in ob mRNA levels nor an
      effect of testosterone. We conclude that leptin gene expression in rat pituitary
      gland is sexually dimorphic and sensitive to neonatal manipulation of sex steroid
      levels.

PMID- 11824510
TI  - Leptin and the pituitary.
AB  - Although leptin was originally viewed as an antiobesity hormone, it is now
      evident that it may have more pleiotropic actions. Experiments in rodents have
      shown that leptin activates the sympathetic nervous system, is involved in
      regulation of blood pressure, hematopoiesis, immune function, angiogenesis and
      brain, bone and pituitary development. Some biological effects expected based on
      observations in rodents, have so far not been seen in humans. Thus due to species
      differences in the role of leptin it is difficult to translate the data from
      rodents to human physiology. Hypothalamus is the primary brain site targeted by
      circulating leptin, secreted by fat cells. Leptin receptor has homology to
      members of class I cytokine receptor family, which may imply similarities in
      molecular events engaged by cytokines and leptin. In view of its cytokine-like
      properties it is likely that leptin produced and secreted outside of fat tissue
      i.e. in other tissues (CNS, pituitary, ovary, placenta, etc), is a paracrine
      regulator. Leptin receptor isoforms, long-signaling and short-nonsignaling, have
      been recently localized in human pituitaries. This opens the possibility of a
      direct action of leptin on the pituitary. However this appears to be quite
      complex and is species dependent. Leptin can be synthesized by normal and
      tumorous pituitary cells. Leptin protein expression in pituitary adenomas is
      decreased compared to that in normal pituitaries. Colocalization studies with
      leptin and anterior pituitary cells showed that 70% of ACTH cells are positive
      for leptin, 21% of GH cells, 29% of LH cells, 33% of FSH cells, 32% of TSH cells,
      64% folliculo-stellate cells whereas very few PRL cells were positive (3%).
      Leptin is stored in secretory granules and secretory cells retain leptin in
      granules until stimulated. This follows a different secretory pathway than in
      adipocytes where upon synthesis leptin is immediately released. Question to be
      raised is does the pituitary contribute to the body leptin pool or is its action
      predominantly paracrine/autocrine? Clinically based evidence from studies
      performed in patients harboring different functional pituitary tumors causing a
      state of hormonal hypersecretion (acromegaly, prolactinomas, Cushing's disease)
      or hypopituitarism (due to non-functioning pituitary adenomas), are in favor of a
      paracrine/autocrine role of the pituitary leptin. Most of the studies have shown
      that the link between leptin, body composition and hormones of the pituitary is
      indirect. Thus changes in levels of circulating leptin are most likely due to
      changes in the metabolic and hormonal milieu during the chronic course of the
      disease or chronic treatment. Furthermore, circadian rhythm of leptin, its
      pulsatility and gender difference are preserved in hypopituitarism as well as in
      patients with functional pituitary adenomas implying that intact hypothalamic
      pituitary function is not essential for leptin's circadian rhythm.

PMID- 11824506
TI  - Leptin and leptin receptor in anterior pituitary function.
AB  - Leptin is a 16 kDa protein that exerts important effects on the regulation of
      food intake and energy expenditure by interacting with the leptin receptor in the
      brain and in many other tissues. Although leptin is produced mainly by white
      adipose tissue, several laboratories have shown low levels of leptin production
      by a growing number of tissues including the anterior pituitary gland. Many
      studies have implicated leptin in anterior pituitary function including the
      observation that homozygous mutations of the leptin receptor gene led to morbid
      obesity, lack of pubertal development and decreased GH and TSH secretion. In
      addition, leptin functions as a neuroendocrine hormone and regulates many
      metabolic activities. Leptin also interacts with and regulates the hypothalamic
      pituitary-adrenal, the hypothalamic-pituitary-thyroid and the hypothalamic
      pituitary-gonadal axes. All of the anterior pituitary cell types express the
      leptin receptor. However, leptin has been localized in specific subtypes of
      anterior pituitary cells indicating cell type-specific production of leptin in
      the anterior pituitary. Subcellular localization of leptin indicates co-storage
      with secretory granules and implicates hypothalamic releasing hormones in leptin
      secretion from anterior pituitary hormone cells. Leptin signal transduction in
      the anterior pituitary has been shown to involve the janus protein-tyrosine
      kinase (JAK)/signal transducer and activation of transcription (STAT) as well as
      suppressor of cytokine signalling (SOCS). These proteins are activated by
      tyrosine-phosphorylation in anterior pituitary cells. The various steps in
      pituitary leptin signal transduction remain to be elucidated.

PMID- 11824511
TI  - Leptin inhibits cortisol and corticosterone secretion in pathologic human
      adrenocortical cells.
AB  - Regulation of adrenal corticosteroid secretion by leptin may involve interactions
      at multiple levels of the hypothalamic-pituitary-adrenal axis. To investigate the
      possible direct effects of leptin on corticosteroid secretion of human
      adrenocortical adenomas, cells from adrenocortical adenomas causing primary
      aldosteronism (n = 1) and Cushing's syndrome (n = 1), as well as cells from
      nonhyperfunctioning adrenocortical adenomas (n = 5) were isolated and incubated
      for 2 h with human recombinant leptin (1-1000 ng/ml) in the presence and absence
      of adrenocorticotrop hormone (ACTH), then cortisol, corticosterone and
      aldosterone concentrations in incubating media were determined using
      radioimmunoassays. It was found that leptin effectively and dose-dependently
      inhibited basal and ACTH-stimulated cortisol and corticosterone secretion in the
      three types of human adrenocortical adenoma cells. The inhibiting effect of basal
      corticosterone secretion was detectable in the presence of leptin concentration
      as low as 1 ng/ml, with decreases of corticosterone secretion to 34+/-4%, 57+/
      11% and 79+/-9% in Cushing's syndrome, primary aldosteronism, and
      nonhyperfunctioning adrenocortical adenoma cells, respectively. The inhibition of
      basal cortisol secretion in the presence of low concentration of leptin was less
      prominent, but 10 ng/ml leptin significantly diminished basal cortisol secretion
      to 81+/-9% in adrenocortical adenoma cells from Cushing's syndrome, to 68+/-6% in
      adenoma cells from primary aldosteronism, and to 83+/-8% in cells from
      nonhyperfunctioning adenomas. The inhibition of ACTH-stimulated cortisol and
      corticosterone secretion by leptin was similar to those found in cells without
      ACTH stimulation. By contrast, leptin even at 1000 ng/ml concentration exerted no
      clear effect on basal and ACTH-stimulated aldosterone secretion in cells from
      primary aldosteronism and in those nonhyperfunctioning adenoma cells in which
      aldosterone secretion was detectable. These results indicate that leptin is a
      potent inhibitor of cortisol and corticosterone secretion in human adenomatous
      adrenocortical cells. The inhibition of these corticosteroids by leptin may
      represent a potentially important interaction that exists between leptin and the
      hypothalamic-pituitary-adrenal axis.

PMID- 11824512
TI  - Leptin and puberty: a review.
AB  - Over the last few years, many studies have focused on leptin, the product of the
      LEP (ob) gene, searching for a possible link between energy balance and
      reproduction. The involvement of this peptide in the regulation of the
      hypothalamo-pituitary-adrenal, gonadal, thyroid and somatotroph axes suggests
      that leptin might play a pivotal role in coordinating the activity of these axes
      and their relationship with the body's energy balance. The effects of leptin on
      hypothalamic, pituitary and peripheral hormone levels, as well as the presence of
      the leptin receptor in a variety of tissues, suggest both an endocrine and a
      paracrine mode of action. Particular attention was paid to the effect of leptin
      on the gonadal axis as infertility, a characteristic feature of both the leptin
      deficient ob/ob mice and the leptin receptor mutant db/db mice, could be
      corrected in ob/ob mice by leptin administration. Considerable leptin level
      changes were observed during puberty both in animal and human studies. A matter
      of controversy is the precise role of leptin in the onset of puberty: is leptin
      the signal that initiates puberty and the accompanying hormonal changes, or has
      leptin only a permissive but key role for the onset of puberty, as likely seems
      to be the case for the maintenance of a functional gonadotroph axis? On current
      evidence, a mainly permissive role seems most probable.

PMID- 11824513
TI  - Leptin and the hypothalamic-pituitary regulation of the gonadotropin-gonadal
      axis.
AB  - Leptin is an adipocyte-derived protein hormone which not only conveys a signal of
      the amount of energy stores to the central nervous system but also plays an
      important role in regulating neuroendocrine function. The importance of leptin in
      the reproductive system has been suggested by the reproductive dysfunction
      associated with leptin deficiency and resistance in both animal models and humans
      as well as the ability of leptin to accelerate the onset of reproductive function
      in normal mice. Transgenic mice overexpressing leptin also have accelerated
      puberty, and leptin administration reverses the fasting-induced suppression of
      sexual maturation in rodents, indicating that leptin may serve as the critical
      link between sufficient energy stores and proper functioning of the reproductive
      system. Normal women have a pulsatile release pattern of leptin that is
      significantly associated with the variations in luteinizing hormone (LH) and
      estradiol levels. In various animal models, leptin administration restores the LH
      pulsatility pattern which is suppressed during fasting, indicating a hypothalamic
      site of action since LH pulsatility is under the control of gonadotropin
      releasing hormone (GnRH). In humans, leptin has been administered to a 9-year-old
      leptin-deficient girl, resulting in a gonadotropin secretory pattern consistent
      with early puberty. While in vitro experiments with hypothalamic explants and a
      GnRH-secreting neuronal cell line have shown that leptin can directly stimulate
      GnRH secretion, the lack of leptin receptors on GnRH neurons suggests that leptin
      may act through other hypothalamic neuropeptides. Several neuropeptides which act
      as downstream effectors of leptin have been investigated, and recent studies
      indicate that cocaine and amphetamine-regulated transcript may be such a mediator
      of leptin's effect on GnRH. Leptin receptors have also been identified in human
      pituitaries, and leptin may influence LH release from the pituitary. However, the
      current evidence is conflicting, and further studies are needed in order to
      clarify leptin's role at the level of the pituitary. Thus, accumulating evidence
      suggests that leptin can regulate gonadotropin levels, and its secretion may, in
      turn, be influenced by GnRH or gonadal steroids but appears to be independent of
      LH control.

PMID- 11824515
TI  - Protection of mouse jejunum against lethal irradiation by Podophyllum hexandrum.
AB  - Radiation induced gastrointestinal damage occurs due to the destruction of the
      clonogenic crypt cells and eventual depopulation and denudation of the villi. P.
      hexandrum, a plant, known for its antitumour activity, has been shown to protect
      the mice against whole body lethal (10 Gy) irradiation. Present study was
      undertaken to investigate the radioprotective effect of P. hexandrum on jejunal
      villi cells, crypt cells, their proliferative capacity and mitigation of
      apoptosis. In an in vivo micro colony survival assay, pre-irradiation
      administration of P. hexandrum (-2 h) increased the number of surviving crypts in
      the jejunum by a factor of 3.0 (P < 0.05) and villi cellularity by 2.7 (P < 0.05)
      fold in comparison to irradiated control. Pre-irradiation administration of P.
      hexandrum reduced the incidence of apoptotic bodies in the crypts (P < 0.05) in a
      time dependent manner and depicted a mitotic arrest till the 24 h. However, after
      84 h the percentage of mitosis was observed to be nearly similar to that of
      unirradiated control. This study suggests that arrest of cell division may help
      in protecting the clonogenic cells against radiation. It would be interesting to
      investigate further the role of P hexandrum in influencing various cell cycle
      regulators like bcl-2, TGF-beta, Cyclin-E etc.

PMID- 11824514
TI  - Leptin, reproduction and sex steroids.
AB  - Leptin is a hormone secreted mainly by the adipose cells with a primary role in
      the regulation of body weight by establishing a feedback loop between the energy
      reserves and the hypothalamic centers that control food intake. Recent data
      suggest that, in addition, leptin interacts with other endocrine systems to
      provide critical information about the size of the fat stores, acting as a
      permissive factor that allows the triggering of energy-demanding situations, as
      the onset of puberty and the reproduction, only when the size of the fuel reserve
      is large enough to guarantee its success. In addition, leptin appears to play a
      role during pregnancy and lactation, as it is produced by the placenta and is
      present in maternal milk. The fact that leptin levels are always higher in
      females, even after correcting for body fat content, suggests that the
      interaction between the adipose tissue and the reproductive system is modulated
      in a different way in males and females by androgenic and estrogenic hormones. In
      fact, adipose tissue samples taken from male donors are completely refractory in
      vitro to the action of both estrogens and androgens. On the contrary,
      dihydrotestosterone, androstenedione and dehydroepiandrosterone-S are potent
      inhibitors of leptin secretion, while estradiol induces a strong stimulation in
      adipose tissue taken from women. Testosterone is devoid of activity in either
      gender.

PMID- 11824516
TI  - Prophylactic and curative effects of Bacopa monniera in gastric ulcer models.
AB  - Bacopa monniera Wettst. (BM, syn. Herpestis monniera L; Scrophulariaceae), is an
      Ayurvedic drug used as a rasayana. Its fresh juice was earlier reported to have
      significant antiulcerogenic activity. In continuation, methanolic extract of BM
      (BME) standardized to bacoside-A content (percentage-38.0 +/- 0.9), when given in
      the dose of 10-50 mg/kg, twice daily for 5 days, showed dose-dependent anti
      ulcerogenic on various gastric ulcer models induced by ethanol, aspirin, 2 h cold
      restraint stress and 4 h pylorus ligation. BME in the dose of 20 mg/kg, given for
      10 days, twice daily showed healing effects against 50% acetic acid-induced
      gastric ulcers. Further work was done to investigate the possible mechanisms of
      its action by studying its effect on various mucosal offensive acid-pepsin
      secretion and defensive factors like mucin secretion, mucosal cell shedding, cell
      proliferation and antioxidant activity in rats. BME 20 mg/kg showed no effect on
      acid-pepsin secretion, increased mucin secretion, while it decreased cell
      shedding with no effect on cell proliferation. BME showed significant antioxidant
      effect per se and in stressed animals. Thus, the gastric prophylactic and
      curative effects of BME may be due to its predominant effect on mucosal defensive
      factors.

PMID- 11824517
TI  - Immunomodulatory effect of Tylophora indica on Con A induced lymphoproliferation.
AB  - Our preliminary studies with tylophora alkaloids had shown that they inhibit
      cellular immune responses like contact sensitivity to dinitro-flurobenzene and
      delayed hypersensitivity to sheep red blood cells, in vivo. Investigations were
      hence carried out to determine the cellular targets of tylophora alkaloids in in
      vitro systems. Con A induced proliferation of splenocytes was used as a model
      system to study the effect of the alkaloids on cellular immune responses. The
      alkaloid mixture was found to inhibit proliferation of splenocytes at higher
      concentrations and augment the same at lower concentrations. Both macrophages and
      T cells were found to be vulnerable to tylophora alkaloids. The alkaloid mixture
      suppressed IL-2 production in Con A stimulated splenocytes at the inhibitory or
      higher concentrations and enhanced production at the lower concentrations. IL-1
      production by activated macrophages on the contrary was doubled in the presence
      of inhibitory concentrations of tylophora. These studies indicate that tylophora
      alkaloids have a concentration dependent biphasic effect on Con A induced
      mitogenesis. At lower concentrations they augment Con A induced
      lymphoproliferation by enhancing IL-2 production. Inhibition of proliferation at
      higher concentrations of the alkaloid is due to inhibition of IL-2 production and
      activation of macrophages, which have a cytostatic effect.

PMID- 11824518
TI  - Cytoprotective and immunomodulatory properties of Geriforte, a herbomineral
      preparation, in lymphocytes.
AB  - The study was designed to determine the cytoprotective and immunomodulatory
      properties of Geriforte, an indigenous herbomineral compound, using lymphocytes
      as a model system. The possible involvement of free radicals and the ability of
      Geriforte to inhibit the oxidative process induced by tert-butylhydroperoxide
      (tert-BHP) was also investigated. The production of free radicals (evaluated by
      fluorescent probe fluorescein-diacetate), level of malondialdehyde (MDA, as index
      of lipid peroxidation), and levels of anti-oxidants--reduced glutathione (GSH)
      and glutathione peroxidase (GPx) were determined. There was an increase in
      cytotoxicity and apoptosis significantly in the presence of tert-BHP (100 microM)
      over control. Addition of tert-BHP resulted in a marked increase in free radical
      production and MDA level with a concomitant decrease in GSH level in lymphocytes.
      Geriforte supplementation reduced cytotoxicity and apoptosis induced by tert-BHP.
      Further, Geriforte inhibited tert-BHP induced lipid peroxidation and maintained
      higher anti-oxidant levels. tert-BHP significantly inhibited the lymphocyte
      proliferation stimulated by mitogens (Lipopolysaccharide/Concanavalin A) and
      enhanced DNA fragmentation. Geriforte relieved the inhibitory effect of tert-BHP
      on lymphocyte proliferation and decreased DNA fragmentation appreciably. The
      results indicate that Geriforte possesses cytoprotective and immunomodulatory
      properties which could be due to its anti-oxidant activity.

PMID- 11824519
TI  - Characterization of human monocyte activation by a water soluble preparation of
      Aphanizomenon flos-aquae.
AB  - Aphanizomenon flos-aquae (AFA) is a fresh-water microalgae that is consumed as a
      nutrient-dense food source and for its health-enhancing properties. The current
      research characterizes the effect of a water soluble preparation from AFA on
      human monocyte/macrophage function and compares the effect of AFA with responses
      from known agents that modulate the immune system. At 0.5 pg/ml the AFA extract
      robustly activated nuclear factor kappa B (NF-kappa B) directed luciferase
      expression in THP-1 human monocytic cells to levels at 50% of those achieved by
      maximal concentrations (10 microg/ml) of bacterial lipopolysaccharide (LPS). In
      addition, the AFA extract substantially increased mRNA levels of interleukin
      1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha), and enhanced the
      DNA binding activity of NF-kappa B. The effects of AFA water soluble preparation
      were similar to the responses displayed by LPS, but clearly different from
      responses exhibited by tetradecanoyl phorbol acetate (TPA) and interferon-gamma
      (INF-gamma). Pretreatment of THP-1 monocytes with factors known to induce
      hyporesponsiveness suppressed both AFA-dependent and LPS-dependent activation.
      These results suggest that the macrophage-activating properties of the AFA water
      soluble preparation are mediated through pathways that are similar to LPS
      dependent activation.

PMID- 11824520
TI  - Antioxidant properties of 8.0.4'-neolignans.
AB  - A series of naturally occurring 8.0.4'-neolignans (1a-d, 1g, 2g, 2h) and their
      analogues (le-f, lh, 1i, 2a-f, 2i) have been synthesized in racemic form starting
      from commercially available phenols, such as eugenol, isoeugenol and 4-allyl-2,6
      dimethoxyphenol and from aromatic aldehydes, such as piperonal, veratraldehyde
      and 3,4,5-trimethoxybenzaldehyde. The inhibitory activity of these compounds on
      superoxide anion (O2.-) release by human polymorphonuclear leukocytes (PMNLs) was
      tested and the structure-activity relationship was also studied.

PMID- 11824522
TI  - Effect of perezone, aminoperezone and their corresponding isomers isoperezone and
      isoaminoperezone upon in vitro platelet aggregation.
AB  - The effect on platelet aggregation of perezone, isoperezone, aminoperezone and
      isoaminoperezone has been determined in human platelets, using
      adenosinediphosphate (ADP), epinephrine and collagen as inducers. Perezone
      inhibited ADP- epinephrine- and collagen-induced platelet aggregation;
      isoperezone, aminoperezone and isoaminoperezone did not. The difference in
      biological responses could be the result of their structures. While isoperezone,
      aminoperezone and isoaminoperezone have carbonyl groups in the vicinity of other
      functional groups, this is not the case for perezone, in which one of the
      carbonyl groups has an adjacent free position.

PMID- 11824521
TI  - Antiallergic effect of ardisiaquinone A, a potent 5-lipoxygenase inhibitor.
AB  - The antiallergic effects of ardisiaquinone A, a potent 5-lipoxygenase inhibitor,
      were examined. Pretreatment with ardisiaquinone A (0.1-10 microM) significantly
      inhibited compound 48/80-induced production of cysteinyl-leukotrienes (cys-LTs;
      LTC4, LTD4 and LTE4) in rat peritoneal mast cells, but not histamine release. The
      IC50 value was 5.56 microM. Pre-administration with ardisiaquinone A (0.1-1
      mg/kg, s.c.) dose-dependently inhibited rat homologous passive cutaneous
      anaphylaxis (PCA) and the maximal inhibitory ratio was 22.3 +/- 3.9% at the dose
      of 1 mg/kg. Ardisiaquinone A (1-5 mg/kg, s.c.) dose-dependently prevented the
      allergen-induced increase of tracheal pressure in ovalbumin-sensitized guinea
      pigs, especially during the late phase. In conclusion, the findings of this study
      show that 5-lipoxygenase inhibitor ardisiaquinone A partially attenuates the
      allergen-induced increases of vascular permeability and tracheal pressure via the
      inhibition of cys-LTs production in mast cells.

PMID- 11824523
TI  - Study on the diuretic activity of Strychnos potatorum Linn. seed extract in
      albino rats.
AB  - Methanol extract of Strychnos potatorum Linn. seeds (SPSE) was evaluated for its
      diuretic activity in Wistar albino rats. The SPSE was administered at the graded
      doses of 200, 400, and 600 mg/kg body weight. The parameters which were taken
      into account during the experimental on each rat were: total urine volume
      (corrected for water intake during the test period), body weight before and after
      the experiment, and the concentration of sodium, potassium, and chloride ions in
      urine. The total urine volumes of the SPSE (600 mg/kg)-treated rats were
      evaluated nearly two and half fold then compared with the control (saline
      treated) group. Excretion of cations (sodium and potassium ions) and anions
      (chloride ions) also increased significantly with respect to the control group.
      The diuretic effect was comparable with that of the standard drug Furosemide. The
      increase of cations in the urine on treatment with Strychnospotatorum seed
      extract (SPSE) was dose-dependent. This effect supports the use of the Strychnos
      potatorum seeds as a diuretic in folk remedies.

PMID- 11824524
TI  - Evaluation of psychopharmacological effects of Clerodendrum phlomidis Linn.
      extract.
AB  - The methanolic extract of Clerodendrum phlomidis Linn. (MECP) leaves was
      evaluated for its psychopharmacological activities in several experimental models
      using Swiss albino mice and Wistar albino rats. The MECP was found to cause
      significant reduction in spontaneous activity, and decreases in exploratory
      behavioral profiles by the Y-maze and head dip test. It also showed reduction in
      muscle relaxant activity by rotarod, 30 degrees inclined screen and traction
      tests, as well as significantly potentiated the phenobarbitone sodium-induced
      sleeping time in the doses examined (200, 400 and 600 mg/kg body wt.). All the
      results were compared with respective controls for the evaluation of
      significance.

PMID- 11824525
TI  - In vitro antiviral effect of flavonoid-rich extracts of Vitex polygama
      (Verbenaceae) against acyclovir-resistant herpes simplex virus type 1.
AB  - Extracts and fractions rich in flavonoids from fruits and leaves of Vitex
      polygama Cham. (Verbenaceae) were tested against acyclovir-resistant herpes
      simplex virus type 1 (ACV-HSV-1). Both fruit and leaf extracts exhibited a dose
      dependent antiviral activity. The extract from the leaves showed intracellular
      antiviral activity while the extract from the fruits had virucidal effect. A
      fraction from the ethyl actetate extract of the leaves inhibited virus
      propagation by blocking HEp-2 cell receptors.

PMID- 11824527
TI  - An antiproliferative norditerpene dilactone, Nagilactone C, from Podocarpus
      neriifolius.
AB  - An ethanolic extract of Podocarpus neriifolius D. Don (Podocarpaceae) showed
      antiproliferative activity against two major tumor cell lines, viz. human HT-1080
      fibrosarcoma and murine color 26-L5 carcinoma. Bioassay guided fractionation
      showed the highest antiproliferative activity in chloroform-soluble fraction.
      Nagilactone C, the major constituent of this fraction was isolated and
      characterized by using NMR, IR and FAB-MS spectroscopic methods. Nagilactone C
      possessed potent antiproliferative activity against human fibrosarcoma and murine
      colon carcinoma tumor cell lines exhibiting ED50 values of 2.3 and 1.2 microg/ml,
      respectively. Hence, nagilactone C could be the active constituent present in
      this plant.

PMID- 11824526
TI  - Natural products isolated from Mexican medicinal plants: novel inhibitors of
      sulfotransferases, SULT1A1 and SULT2A1.
AB  - Calophyllum brasiliense, Lonchocarpus oaxacensis, and Lonchocarpus guatemalensis
      are used in Latin American folk medicine. Four natural xanthones, an acetylated
      derivative, and two coumarins were obtained from C. brasiliense. Two flavanones
      were extracted from L. oaxacensis and one chalcone from L guatemalensis. These
      compounds were tested as substrates and inhibitors for two recombinant
      sulfotransferases (SULTs) involved in the metabolism of many endogenous compounds
      and foreign chemicals. Assays were performed using recombinant
      phenolsulfotransferase (SULT1A1) and hydroxysteroidsulfotransferase (SULT2A1).
      Three of the five xanthones, one of the flavonoids and the coumarins tested were
      substrates for SULT1A1. None of the xanthones or the flavonoids were sulfonated
      by SULT2A1, whereas the coumarin mammea A/BA was a substrate for this enzyme. The
      natural xanthones reversibly inhibited SULT1A1 with IC50 values ranging from 1.6
      to 7 microM whereas much higher amounts of these compounds were required to
      inhibit SULT2A1 (IC50 values of 26-204 microM). The flavonoids inhibited SULT1A1
      with IC50 values ranging from 9.5 to 101 microM, which compared with amounts
      needed to inhibit SULT2A1 (IC50 values of 11 to 101 microM). Both coumarins
      inhibited SULT1A1 with IC50 values of 47 and 185 pM, and SULT2A1 with IC50 values
      of 16 and 31 microM. The acetylated xanthone did not inhibit either SULT1AI or
      SULT2A1 activity. Rotenone from a commercial source had potency comparable to
      that of the flavonoids isolated from Lonchocarpus for inhibiting both SULTs. The
      potency of this inhibition depends on the position and number of hydroxyls. The
      results indicate that SULT1A1, but not SULT2A1, is highly sensitive to inhibition
      by xanthones. Conversely, SULT2A1 is 3-6 times more sensitive to coumarins than
      SULT1A1. The flavonoids are non-specific inhibitors of the two SULTs.
      Collectively, the results suggest that these types of natural products have the
      potential for important pharmacological and toxicological interactions at the
      level of phase-II metabolism via sulfotransferases.

PMID- 11824528
TI  - Downregulation of p34cdc2 expression with aqueous fraction from Withania
      somnifera for a possible molecular mechanism of anti-tumor and other
      pharmacological effects.

PMID- 11824529
TI  - Some reflections on the NICE appraisal of hearing aid technology. National
      Institute for Clinical Excellence.

PMID- 11824530
TI  - Systematic review of the clinical and cost effectiveness of digital hearing aids.
AB  - The aim of the present study was to systematically review the clinical and cost
      effectiveness of hearing aids which use digital signal processing relative to
      other forms of hearing aid technology, in particular analogue-based aids. A
      comprehensive search for randomized controlled trials, randomized crossover
      trials and economic studies was undertaken. Trial quality assessment and data
      extraction were undertaken by two independent reviewers. Eight trials comparing
      digital to non-digital devices were identified--one randomized controlled trial
      and seven randomized crossover trials. The majority of these studies were of
      small sample size and of poor methodological quality. In the majority of cases
      (nine out of 13), there was no evidence of a significant difference in either
      laboratory scores (nine out of 13 outcomes assessed) or user function/quality of
      life scores (six out of nine outcomes assessed) between digital and non-digital
      devices. In addition, there was no significant difference in patient preference
      for digital compared to control aids (relative risk 1.93; 95% CI 0.70-5.35) when
      pooled across studies. No cost-effectiveness studies directly comparing digital
      to non-digital devices were identified. In conclusion, the evidence identified by
      this review provides no significant evidence of the clinical benefit of digital
      devices compared to analogue-based aids. However, these results are difficult to
      generalize to current UK practice as the analogue aids and types of fitting in
      the trials are not those typically used in the NHS.

PMID- 11824531
TI  - The hearing aid 'effect' revisited in young adults.
AB  - Hearing impairment is a common ailment in older adults. However, the acceptance
      of hearing aids by hearing-impaired individuals remains poor. The main reasons
      given by hearing-impaired individuals for not acquiring a hearing aid are
      primarily psychosocial in nature. Research suggests that individuals with hearing
      loss believe that wearing hearing aids will cause them to be perceived as old
      and/or less competent. The purpose of the present study was to determine the
      perceptions of young adults towards hearing loss and hearing aids and to compare
      them to the perceptions of older adults with hearing impairment. A version of the
      'Attitudes Toward Loss of Hearing Questionnaire' was administered to young adults
      and older adults with hearing loss. Results suggest that young adults do not
      associate hearing aids with ageing or diminished cognitive function, although
      findings suggest reticence towards wearing amplification. The implications of
      this study are discussed in terms of increasing public awareness of hearing loss.

PMID- 11824532
TI  - Use of the 'real-ear to dial difference' to derive real-ear SPL from hearing
      level obtained with insert earphones.
AB  - The electroacoustic characteristics of a hearing instrument are normally selected
      for individuals using data obtained during audiological assessment. The precise
      inter-relationship between the electroacoustic and audiometric variables is most
      readily appreciated when they have been measured at the same reference point,
      such as the tympanic membrane. However, it is not always possible to obtain the
      real-ear sound pressure level (SPL) directly if this is below the noise floor of
      the probe-tube microphone system or if the subject is unco-operative. The real
      ear SPL may be derived by adding the subject's real-ear to dial difference (REDD)
      acoustic transform to the audiometer dial setting. The aim of the present study
      was to confirm the validity of the Audioscan RM500 to measure the REDD with the
      ER-3A insert earphone. A probe-tube microphone was used to measure the real-ear
      SPL and REDD from the right ears of 16 adult subjects ranging in age from 22 to
      41 years (mean age 27 years). Measurements were made from 0.25 kHz to 6 kHz at a
      dial setting of 70 dB with an ER-3A insert earphone and two earmould
      configurations: the EAR-LINK foam ear-tip and the subjects' customized skeleton
      earmoulds. Mean REDD varied as a function of frequency but was typically
      approximately 12 dB with a standard deviation (SD) of +/- 1.7 dB and +/- 2.7 dB
      for the foam ear-tip and customized earmould, respectively. The mean test-retest
      difference of the REDD varied with frequency but was typically 0.5 dB (SD 1 dB).
      Over the frequency range 0.5-4 kHz, the derived values were found to be within 5
      dB of the measured values in 95% of subjects when using the EAR-LINK foam ear-tip
      and within 4 dB when using the skeleton earmould. The individually measured REDD
      transform can be used in clinical practice to derive a valid estimate of real-ear
      SPL when it has not been possible to measure this directly.

PMID- 11824533
TI  - Comparison of the electroacoustic characteristics of five hearing aids.
AB  - This paper describes a comparison of the electroacoustic characteristics of five
      hearing aids: (1) a linear BTE aid of the type dispensed under the UK National
      Health Service (NHS), the BE19; (2) an analogue programmable BTE aid
      incorporating two-channel wide dynamic range compression, the ReSound BT2; (3)
      and (4) two digital BTE aids incorporating multi-channel wide dynamic range
      compression, the Phonak Claro and the Danavox Danalogic; (5) a disposable ITE
      hearing aid with single-channel compression, the Songbird. Measurements of
      frequency response using a 2 cc coupler showed that the NHS aid had a distinct
      undesired peak around 1 kHz. The response rolled off at low and high frequencies,
      and no gain was applied above about 4000 Hz. The BT2 and Claro both showed
      somewhat irregular responses with effective upper frequency limits of 5000-6000
      Hz. The Danalogic had a reasonably smooth response and provided gain up to 6000
      Hz. The Songbird had a smooth response and provided gain up to about 7000 Hz. All
      aids showed reasonably low harmonic and intermodulation distortion (probably
      below audible levels for hearing-impaired listeners), the Phonak Claro being the
      best in this respect. Measures of the effective input noise were obtained using
      two new methods. The NHS aid had the highest (worst) effective input noise,
      whereas the Songbird had the lowest, especially at low frequencies. The BT2 and
      the two digital aids had similar noise levels on one measure, but the BT2 was
      superior on the other measure. The compression circuits were characterized by
      measuring attack and release times and by using a method described by Stone and
      Moore (1992). The aids varied markedly in the extent to which they compressed
      amplitude modulation at the rates typically occurring in speech (2-10 Hz), the
      Claro providing the least compression and the Danalogic and Songbird aids
      providing the most. Overall, the results indicate that the NHS aid performed more
      poorly in several respects than the other aids. There were no great differences
      in electroacoustic characteristics between the remaining analogue aids and the
      digital aids, although the Songbird had a somewhat wider frequency range and
      lower effective input noise than the other aids.

PMID- 11824534
TI  - Sesquiterpenes from Jasonia glutinosa: in vitro anti-inflammatory activity.
AB  - Four sesquiterpenes isolated from Jasonia glutinosa D.C. (Asteraceae), namely
      lucinone, glutinone, 5-epi-kutdtriol and kutdtriol, have been evaluated for their
      in vitro anti-inflammatory activity in cellular systems generating cyclooxygenase
      (COX) and 5-lipoxygenase (5-LOX) metabolites. None of the compounds assayed had a
      significant effect on leukotriene C4 (LTC4)-release from calcium ionophore
      stimulated mouse peritoneal cells. However, the release of prostaglandin E2
      (PGE2) by mouse peritoneal cells stimulated with calcium ionophore was inhibited
      by these compounds, although with less potency than the reference drug
      indomethacin (IC50=0.24 microM). The IC50 values of the active compounds were:
      lucinone 42.69 microM, glutinone 3.61 microM, 5-epi-kutdtriol 1.28 microM and
      kutdtriol 39 microM. Of the tested compounds, only glutinone (IC50=24 microM)
      showed a significant effect on thromboxane B2 (TXB2)-release induced by calcium
      ionophore in human platelets, although with less potency than the reference drug
      ibuprofen (IC50=1.27 microM).

PMID- 11824535
TI  - An investigation of the antiinflammatory effects of an extract from Cladonia
      rangiformis HOFFM.
AB  - In this study, the antiinflammatory effects of 50, 100 and 200 mg/kg doses of
      extract obtained from Cladonia rangiformis, so-called C-1, were investigated. The
      effects of C-1 on the acute phase of inflammation were studied in formaldehyde
      induced edema. A cotton-pellet granuloma test was used to investigate the effects
      of C-1 on chronic inflammation. The antiedema potency of C-1 was compared with
      indomethacin. C-1 at the doses mentioned above showed 33.8% (p<0.005), 36.1%
      (p<0.005), 43.1% (p<0.001) inhibition, respectively. The corresponding
      antiinflammatory effect for indomethacin was determined as 72% (p<0.001). 200
      mg/kg C-1 and 10 mg/kg indomethacin decreased the formation of granuloma tissue
      induced by cotton-pellet method at a rate of 57.3% (p<0.005) and 52.1% (p<0.005),
      respectively. It was seen that C-1 was more effective on chronic inflammation
      than on acute inflammation.

PMID- 11824536
TI  - Isolation and characterization of alkyl peroxy radical scavenging compound from
      leaves of Laurus nobilis.
AB  - EtOH-soluble fraction from leaves of Laurus nobilis (bay leaves) possessed the
      highest alkyl peroxy radical (ROO*) scavenging activity among 120 kinds of herbs
      and edible plants, using the bioassay system which could determine the viability
      of Staphylococcus aureus 209p by ROO* cytotoxicity. After EtOH-soluble fraction
      was partitioned with chloroform, ethylacetate, n-butanol and water, the
      ethylacetate-soluble fraction (L-EA) possessing the highest scavenging activity
      was further fractionated by Silica gel, Sephadex LH-20 and semi-preparative HPLC
      analysis on micro-Bondapak C18 reverse phase, and a major flavonol (L-EA-IIa-3
      H2) in leaves of L. nobilis was isolated. According to the ultraviolet-visible
      absorption spectra, L-EA-IIa-3-H2 was thought to be 3,5,7,3'-OH or 3(5),7,3',4'
      OH flavonol. After acid hydrolysis of the fraction, L-EA-IIa-3-H2 was found to
      consist of quercetin and glucose, and was confirmed by one- or two-dimensional
      (1D or 2D)-NMR to be isoquercitrin. In addition, the ROO* scavenging activity of
      L-EA-IIa-3-H2 was supported by ESR and its activity was found to be comparable to
      that of other well-known antioxidants such as epigallocatechin and resveratrol,
      and higher than that of butylated hydroxyanisole (BHA), butylated hydroxytoluene
      (BHT) and ascorbic acid.

PMID- 11824537
TI  - Apoptosis in cultured human fetal membrane cells infected with influenza virus.
AB  - We investigated the induction of apoptosis in cultured human fetal membrane cells
      infected with influenza virus type A. We found that influenza virus yield in
      supernatants of primary cultured chorion and amnion cells prepared from human
      fetal membranes increased 6 h after infection. Chromosomal DNA was fragmented
      into oligonucleosomes at 48 h after influenza virus infection in chorion cells
      but not in mock-infected chorion cells, mock-infected amnion cells or influenza
      virus-infected amnion cells. The DNA fragmentation in influenza virus-infected
      chorion cells was evident at 24 h after infection and depended on the
      multiplicity of infection at 48 h. Incubating influenza virus-infected chorion
      cells with ribavirin, an inhibitor of viral RNA synthesis, reduced the increase
      in virus yield and simultaneously blocked DNA fragmentation. These results
      suggest that both chorion and amnion cells become infected with influenza virus,
      but that influenza virus infection induces apoptosis in chorion, but not typical
      apoptosis characterized by DNA ladder formation in amnion cells. We further
      observed that influenza virus replication is associated with the induction of
      apoptosis.

PMID- 11824538
TI  - Expression of a synthetic gene encoding the Asp-hemolysin from Aspergillus
      fumigatus in Escherichia coli.
AB  - Asp-hemolysin is a hemolytic toxin from Aspergillus fumigatus and is a specific
      binding protein with high affinity for oxidized low density lipoprotein (Ox-LDL).
      As a first step in clarifying the structure-function relationship of Asp
      hemolysin, we expressed Asp-hemolysin in Escherichia coli (E. coli) as a fusion
      protein with a maltose-binding protein (MBP) and purified it by affinity
      chromatography on an amylose resin. The apparent molecular size of the protein
      produced by E. coli was approximately 57 kDa, as determined by polyacrylamide gel
      electrophoresis in the presence of sodium dodecyl sulfate. This is consistent
      with the predicted molecular size of 56.9 kDa for a fusion protein which includes
      14.2 kDa of Asp-hemolysin and 42.7 kDa from MBP. The purified recombinant Asp
      hemolysin showed an immunoreactivity with the anti-Asp-hemolysin antibody as
      revealed by western blot analysis. Furthermore, in dot blot analysis, MBP-Asp
      hemolysin fusion protein exhibited binding activity to Ox-LDL as did native Asp
      hemolysin.

PMID- 11824539
TI  - Characterization of human lactoferricin as a potent protein kinase CK2 activator
      regulated by A-kinase in vitro.
AB  - Lactoferricin (LFcin) hydrolyzed from lactoferrin (LF), a major 80 kDa iron
      binding protein in milk and other exocrine secretions, was characterized as a
      potent activator of protein kinase CK2 (CK2) in vitro. Human LFcin (hLFcin) at
      0.5 microg stimulated approx. 5-fold CK2 activity [phosphorylation of 60S acidic
      ribosomal proteins (P0, P1, P2) and Hsp90 (p98)] in a manner similar to other
      functional proteins with oligo-Arg clusters, such as salmine A1, sperm histone
      H2B and HIV-1 Rev. Interestingly, this stimulatory effect of hLFcin was
      significantly reduced when it was phosphorylated by A-kinase in vitro. These
      results suggest that (i) hLFcin acts as a potent CK2 activator in vitro; and (ii)
      the stimulatory effect of hLFcin on CK2 activity is regulated by its
      phosphorylation by A-kinase in vitro.

PMID- 11824540
TI  - Mechanism of inhibition of small intestinal motility by restraint stress differs
      from that with norepinephrine treatment in rats.
AB  - We have previously reported that restraint stress inhibits small intestinal
      motility in rats, and that the adrenergic beta3-antagonist SR59230A
      administration recovered the inhibition. In the present study, we compared the
      effects of restraint stress and norepinephrine on small intestinal motility using
      alpha- and beta-adrenergic antagonists. SR59230A did not recover the
      norepinephrine-induced inhibition of small intestinal motility. The
      norepinephrine-induced inhibition of small intestinal motility was recovered
      after administration of the alpha2-antagonist yohimbine, but not by alpha1-,
      beta1-, and beta2-antagonists. Considering these results, it is reasonable to
      assume that the mechanisms of inhibition of small intestinal motility due to
      restraint stress and norepinephrine treatment are different.

PMID- 11824541
TI  - (+)-Alpha-viniferin, a stilbene trimer from Caragana chamlague, inhibits
      acetylcholinesterase.
AB  - In the course of screening natural products for anti-acetylcholinesterase (AChE)
      activity, we found that a total methanolic extract of the underground parts of
      Caragana chamlague (Leguminosae) had significant inhibition towards AChE.
      Bioactivity-guided fractionation of the total methanolic extract resulted in the
      isolation and identification of two active stilbene oligomers, (+)-alpha
      viniferin (1) and kobophenol A (2). Both 1 and 2 inhibited AChE activity in a
      dose-dependent manner, and the IC50 values of 1 and 2 were 2.0 and 115.8 microM,
      respectively. The AChE inhibitory activity of 1 was specific, reversible and
      noncompetitive.

PMID- 11824542
TI  - Modulation of radioligand binding to the GABA(A)-benzodiazepine receptor complex
      by a new component from Cyperus rotundus.
AB  - Four sesquiterpenes, beta-selinene, isocurcumenol, nootkatone and aristolone and
      one triterpene, oleanolic acid were isolated from the ethylacetate fraction of
      the rhizomes of Cyperus rotundus and tested for their ability to modulate gamma
      aminobutyric acid (GABA(A))-benzodiazepine receptor function by radioligand
      binding assays using rat cerebrocortical membranes. Among these compounds, only
      isocurcumenol, one of the newly identified constituents of this plant, was found
      to inhibit [3H]Ro15-1788 binding and enhance [3H]flunitrazepam binding in the
      presence of GABA. These results suggest that isocurcumenol may serve as a
      benzodiazepine receptor agonist and allosterically modulate GABAergic
      neurotransmission via enhancement of endogenous receptor ligand binding.

PMID- 11824543
TI  - Leishmanicidal effect of curcumin in vitro.
AB  - From a study to find anti-parasitic agents from natural resources, we found that
      curcumin showed the cytotoxicity against leishmania in vitro. The LD50 value of
      this activity was 37.6+/-3.5 microM.

PMID- 11824544
TI  - In vitro skin permeation of morphine hydrochloride during the finite application
      of penetration-enhancing system containing water, ethanol and l-menthol.
AB  - The effects of composition of applied solutions, containing water, ethanol (EtOH)
      and l-menthol (LM) as penetration enhancers, on the in vitro permeation of
      morphine hydrochloride (MPH) through excised hairless rat skin were examined in
      finite application experiments. Three of the five different applied solutions
      contained almost saturated LM and two contained levels of LM below the limit of
      solubility. Despite similar pseudo steady-state fluxes (maximum fluxes observed)
      of MPH from the solutions, lag time for the permeation of MPH from the saturated
      systems was shorter than that from the unsaturated systems. Lag times for the
      permeation of EtOH and LM from the saturated systems were also shorter than those
      from the unsaturated systems. Thermodynamic activity of LM is important for the
      enhancing effect against MPH permeation. At the beginning for the permeation
      experiment, the activity of LM in the unsaturated systems was lower than that in
      the saturated solutions. As the skin permeability of EtOH was higher than that of
      other components, the content of EtOH in the applied solution gradually decreased
      with time, while the activity of LM increased eventually showing a sufficient
      enhancing effect. Solvent drag effect was not important for the permeation of
      MPH, since penetration rate of MPH was independent of the time course of that of
      EtOH. The amount of LM migrating into skin appeared to be the most important
      parameter for the penetration-enhancing effect of the mixed system in the in
      vitro permeation of MPH through excised hairless rat skin.

PMID- 11824545
TI  - Antipruritic effects of 1,4-naphthoquinones and related compounds.
AB  - The antipruritic effects of orally administered 1,4-naphthoquinone derivatives
      and related compounds on compound 48/80-induced scratching behavior in mice were
      studied. 2-Hydroxy-3-(2-hydroxyethyl)-1,4-naphthoquinone, ferulic acid, 2,2'
      methylenebis(3-hydroxy-1,4-naphthoquinone), and 2,2'-ethylidenebis(3-hydroxy-1,4
      naphthoquinone) (impatienol) all exhibited significant antipruritic activity.
      However, 2-methoxy-3-(2-hydroxyethyl)-1,4-naphthoquinone (balsaquinone), which
      was isolated from a natural source for the first time, did not show any activity.
      The present results indicate that these compounds are promising for treating
      allergic diseases with chronic and severe pruritus.

PMID- 11824546
TI  - Mechanisms of gastric mucus secretion from cultured rat gastric epithelial cells
      induced by carbachol, cholecystokinin octapeptide, secretin, and prostaglandin
      E2.
AB  - The effects of carbachol, cholecystokinin octapeptide (CCK-8), secretin,
      prostaglandin E2 (PGE2), and second mediator-like substances (A23187, phorbol 12
      myristate 13-acetate, and dibutyryl cAMP) on mucus secretion from cultured
      gastric epithelial cells were investigated. Gastric mucus was measured by an
      enzyme-linked lectin assay with soybean agglutinin and wheat germ agglutinin.
      Intracellular cAMP and Ca2+ were measured with a cAMP assay kit and an image
      analysis system using fura-2-loaded cells, respectively. Secreted mucus induced
      by any combination of receptor agonists was almost equal to the summation of each
      stimulated mucus secretion. On the other hand, combined stimulation with second
      mediator-like substances secreted mucus synergistically. These results suggest
      the existence of interactions among receptors for mucus secretion. Based on these
      results, the secretagogue induced intracellular cAMP and free calcium ([Ca2+]i)
      levels were measured in cultured gastric epithelial cells incubated with
      secretagogues. Secretin and PGE2 induced cAMP accumulation, and carbachol and CCK
      8 induced a [Ca2+]i increase. To confirm these results, the effects of protein
      kinase A and C inhibitors and intracellular calcium chelator on mucus secretion
      were investigated. An intracellular calcium chelator inhibited the mucus
      secretion induced not only by carbachol and CCK-8 but also by secretin and PGE2.
      These results suggest that the [Ca2+]i plays an important role in mucus secretion
      through cAMP accumulation.

PMID- 11824547
TI  - Synergistic action of beta-glucan and platelets on interleukin-8 production by
      human peripheral blood leukocytes.
AB  - The effects of human platelets on interleukin (IL)-8 production from human
      peripheral blood mononuclear cells (PBMCs) and polymorphonuclear leukocytes
      (PMNs) stimulated with the fungal (1-->3)-beta-D-glucan schizophyllan (SPG) were
      examined using ELISA. PBMCs/PMNs in the presence of platelets and SPG enhanced IL
      8 production in comparison with those in the presence of either platelets or SPG.
      IL-8 production was dependent on the concentration of platelets and incubation
      time, and the activity reached the maximal level at 18 h of incubation. These
      activities were also observed with the addition of platelets prestimulated with
      SPG to PBMCs. Addition of SPG directly enhanced expression of P-selectin on
      platelet membrane surfaces. These results suggest that platelets play a key role
      in the cytokine production of leukocytes induced by fungal (1-->3)-beta-D-glucans
      and might be mediated, at least in part, by P-selectin.

PMID- 11824549
TI  - Vaticanol C, a novel resveratrol tetramer, inhibits cell growth through induction
      of apoptosis in colon cancer cell lines.
AB  - A novel resveratrol tetramer, vaticanol C, isolated from the stem bark of Vatica
      rassak markedly suppressed cell growth through induction of apoptosis, which was
      characterized by nuclear changes and DNA ladder formation, in three different
      human colon cancer cell lines.

PMID- 11824548
TI  - Estrogenic activities of chemicals in diesel exhaust particles.
AB  - In a previous study, we focused on estrogenic activity of the hexane extract of
      diesel exhaust particles (DEP). The extract of hexane was first fractionated to
      acidic, phenolic and neutral portions according to their chemical properties, of
      which the neutral fraction was fractionated by column chromatography on silica
      gel. The chemical structures of compounds in these fractions were then analyzed.
      It was found that the neutral fraction of the hexane extract of DEP contains
      dibenzothiophene derivatives, one of which, 4,6-dimethyldibenzothiophene,
      possesses estrogenic activity.

PMID- 11824550
TI  - The contribution of the pyrogallol moiety to the superoxide radical scavenging
      activity of flavonoids.
AB  - Sixteen flavonoids including flavonols, flavones, flavanonol and catechins, and
      five aromatic compounds were examined for their ability to scavenge superoxide
      radical (O2-*) generated enzymatically in a xanthin-xanthinoxidase system and non
      enzymatically in a phenazine methosulfate-NADH system. Pyrogallol, gallic acid
      and its ester, were much more efficient in scavenging O2-* than catechol. The
      superiority of pyrogallol over catechol in the flavonoidal nucleus is apparent
      from the much higher O2-* scavenging activity of myricetin and epigallocatechin,
      which contain 3',4',5'-trihydroxyl substitution in the B-ring, compared to
      quercetin and epicatechin, which contain 3',4'-dihydroxyl substitution,
      respectively. The strong O2-* scavenging ability of pyrogallol appears to
      function even in the A-ring, as in baicalein, and also in the form of a
      pyrogalloyl ester at the C-3 position in the C-ring, as in epicatechin gallate
      and epigallocatechin gallate. It can be concluded that the pyrogallol moiety is
      an active component of flavonoids for displaying high O2-* scavenging activity.
      Flavonoids and aromatics were also examined to correlate their O2-* scavenging
      activity with their oxidizability, which was measured on the basis of
      electrochemical redox potential and the reducing ability of the Cu2+ ion.
      Aromatics such as pyrogallol, gallic acid and its ester, and flavonoids such as
      baicalein, epicatechin gallate and epigallocatechin gallate, in which the O2-*
      scavenging activity is enhanced by the presence of a pyrogallol moiety which does
      not belong to the B-ring, reduced the correlation between the higher O2-*
      scavenging activity and the lower redox potential. The O2-* scavenging activity
      was well correlated with the Cu2+ reducing ability of flavonoids and aromatics.

PMID- 11824551
TI  - In vivo measurement of 1,4-dihydropyridine receptors in mesenteric arteries of
      spontaneously hypertensive rats and effect of nifedipine and cilnidipine.
AB  - The present study was undertaken to measure 1,4-dihydropyridine (DHP) receptor
      binding sites in vivo in the mesenteric artery and other tissues of spontaneously
      hypertensive rats (SHR) and to examine the effect of nifedipine and cilnidipine.
      Specific in vivo binding of (+)-[3H]PN 200-110 in the SHR mesenteric artery was
      dose dependently reduced by oral administration of nifedipine at relatively low
      doses. Oral administration of cilnidipine (6.09 micromol/kg) significantly
      reduced the specific in vivo binding of (+)-[3H]PN 200-110 in the mesenteric
      artery, aorta, and myocardium. A significant reduction in (+)-[3H]PN 200-110
      binding was seen at 1-12 h in the mesenteric artery and at 1-7 h in the aorta and
      myocardium. In contrast, oral administration of nifedipine (28.9 micromol/kg)
      markedly reduced in vivo (+)-[3H]PN 200-110 binding in all tissues of SHR at 1-6
      h, and the degree and time course of the reduction did not differ much among the
      tissues. The area under the curve (AUC) for receptor occupancy vs. time was
      calculated from the reduction rate (%) of specific in vivo (+)-[3H]PN 200-110
      binding. The ratio (1.4 or 1.7) of the AUC(mesenteric artery) to AUCaorta or
      AUCmyocardium after oral administration of cilnidipine was greater than the
      corresponding value (1.1) for nifedipine. In conclusion, the present study
      demonstrates that cilnidipine, but not nifedipine, may occupy 1,4-DHP receptors
      in the small artery in a more selective and sustained manner than in other
      tissues of SHR, and thus such receptor binding specificity may be responsible for
      the long-lasting hypotensive effect of this drug.

PMID- 11824552
TI  - N-terminal acylation of somatostatin analog with long chain fatty acids enhances
      its stability and anti-proliferative activity in human breast adenocarcinoma
      cells.
AB  - The anti-proliferative activity of the somatostatin analog RC-160 is limited by
      its short serum half life. To circumvent this limitation, fatty acids of chain
      lengths ranging from 4 to 18 were individually conjugated to the N-terminal
      residue of RC-160. The lipophilized derivatives of RC-160 were synthesized,
      purified and characterized. The anti-proliferative activity of lipophilized-RC
      160 on the human breast carcinoma cell line MCF-7, was evaluated in vitro. The
      long chain lipopeptides like pamitoyl-RC-160 exhibited significantly higher anti
      proliferative activity on MCF-7 cells (p<0.001), relative to RC-160. The affinity
      of RC-160 towards somatostatin receptors remained unaltered by pamitoylation.
      However, the observed increase in bioactivity was manifested within an optimum
      range of chain length of the lipoppetide. Increasing the peptide hydrophobicity
      beyond this range reduced the bioactivity of lipophilized-RC-160. Accordingly,
      stearoyl-RC-160, manifested lower anti-neoplastic activity and receptor affinity
      relative to pamitoyl-RC-160 and RC-160 itself. The signaling pathways underlying
      the antineoplastic activity of these lipopeptides were found to be similar to RC
      160. Pamitoyl-RC-160 displayed enhanced inhibition of protein tyrosine kinase
      activity and intracellular cAMP levels in MCF-7 cells, relative to butanoyl-RC
      160 or RC-160 itself. Pamitoyl-RC-160 also displayed greater resistance towards
      trypsin and serum degradation than RC-160. Lipophilization of RC-160 with long
      chain fatty acids like pamitic acid improves its stability and anti-proliferative
      activity, thereby improving the scope of enhancing its therapeutic index.
      However, the optimization of peptide hydrophobicity seems to be a crucial factor
      governing the efficacy of bioactive lipopeptides.

PMID- 11824553
TI  - Induction of apoptosis in human lung fibroblasts and peripheral lymphocytes in
      vitro by Shosaiko-to derived phenolic metabolites.
AB  - Shosaiko-to is a Kampo medicine used for the treatment of chronic hepatitis in
      Japan. Lately, over 200 cases of interstitial pneumonia have been reported
      resulting from Shosaiko-to therapy, and the number of cases increased when
      patients were administrated interferon (IFN)-alpha at the same time. However, the
      mechanisms of this Shosaiko-to implicated interstitial pneumonia are not fully
      understood. In this study, we examined by flow cytometry analysis the in vitro
      effects of 7 phenolic compounds (lignans and flavonoids), which were detected
      from human urine after administration of Shosaiko-to, and IFN-alpha on inducing
      apoptosis in human lung fibroblasts and peripheral blood mononuclear cells
      (PBMCs). Among the 7 compounds, baicalein and medicarpin (10 microg/ml) showed
      significant apoptosis-inducing effects on human PBMCs. In human lung fibroblasts,
      medicarpin exhibited a significantly higher activity to induce apoptosis compared
      to the control, and the percentage of cells undergoing apoptosis showed time- and
      dose-dependent increases. Baicalein (0.1 and 1 microg/ml), liquiritigenin (10
      microg/ml) and davidigenin (10 microg/ml) also showed significant effects after
      96 h treatment. Whereas, baicalin, oroxylin A and wogonin did not show any effect
      on inducing apoptosis in PBMCs and fibroblasts. Baicalein and medicarpin
      significantly inhibited the growth and reduced the viability of lung fibroblasts.
      IFN-alpha had no apoptosis-inducing effect, and it did not show synergistic
      interaction with any of the compounds derived from Shosaiko-to on inducing
      apoptosis in both human lung fibroblasts and PBMCs. These results suggested that
      phenolic compounds found in human post-administrative urine of Shosaiko-to,
      especially baicalein and medicarpin, exhibited a direct effect on human lung
      fibroblasts and immune cells to induce apoptosis.

PMID- 11824554
TI  - Monkey hepatic microsomal alcohol oxygenase: purification and characterization of
      a cytochrome P450 enzyme catalyzing the stereoselective oxidation of 7alpha- and
      7beta-hydroxy-delta8-tetrahydrocannabinol to 7-oxo-delta8-tetrahydrocannabinol.
AB  - The formation of 7-oxo-delta8-tetrahydrocannabinol (7-Oxo-delta8-THC) from 7alpha
      or 7beta-hydroxy-delta8-THC (7alpha- or 7beta-OH-delta8-THC) was found in
      hepatic microsomes of monkeys. The activity in 7beta-OH-delta8-THC was
      stereoselectively 2.5- to 4.6-fold higher than that from 7alpha-OH-delta8-THC.
      The oxidative activities of 7alpha- and 7beta-OH-delta8-THC to 7-Oxo-delta8-THC
      were inhibited to 35% and 10%, respectively, of the control value by the antibody
      against P450GPF-B (CYP3A), a major enzyme responsible for the formation of 7-Oxo
      delta8-THC in guinea pigs. In the Lineweaver-Burk double-reciprocal plot
      analysis, testosterone 6beta-hydroxylase activity was competitively inhibited by
      7beta-OH-delta8-THC. Two cytochrome P450 enzymes, called P450JM-D and P450JM-E,
      were purified from hepatic microsomes of Japanese monkeys. P450JM-E, assumed to
      be CYP3A8, immunologically reacted with the antibody against P450GPF-B and showed
      high forming activity of 7-Oxo-delta8-THC from 7-OH-delta8-THC. On the other
      hand, 7-Oxo-delta8-THC forming activity of P450JM-D, assumed to be CYP2C, was
      less than 10% of that of P450JM-E (CYP3A8). Oxygen-18 (18O) derived from
      atmospheric oxygen was incorporated into about 40% of the corresponding ketone
      formed from 7alpha-OH-delta8-THC or 8beta-OH-delta9-THC by P450JM-E (CYP3A8),
      although the incorporation of the stable isotope into the oxidized metabolite
      from 7beta-OH-delta8-THC or 8alpha-OH-delta9-THC was negligible. These results
      indicate that P450JM-E (CYP3A8) is a major enzyme of the oxidation of 7-OH-delta8
      THC in monkey hepatic microsomes. The oxidation mechanism may proceed as follows:
      the alpha- and beta-epimers of 7-OH-delta8-THC or 8-OH-delta9-THC may be
      converted to ketone through dehydration of an enzyme-bound gem-diol by P450JM-E
      (CYP3A8), although this stereoselective dehydration differentiates between two
      epimers.

PMID- 11824555
TI  - Interaction of phytoestrogens with estrogen receptors alpha and beta (II).
AB  - We investigated the estrogenic activities of isoflavone derivatives in
      competition binding assays with human estrogen receptor (hER) alpha or hER beta
      protein, and in a gene expression assay using a yeast system. Coumestrol binds as
      strongly as 17beta-estradiol to both hERs. Biochanin A, 5-OMe-genistein,
      formononetin, and tectorigenin bind well to hER beta, but significant binding to
      hER alpha is only observed with 5-OMe-genistein, formononetin and tectorigenin.
      The binding of 7-OMe-genistein and irisolidone is poor to both receptors. Among
      the glucosides, sissotorin binds both receptors and the binding is stronger than
      genistin. Coumestrol induces transcription as strongly as genistein. Tectorigenin
      also induces transcription with both hERs. Though biochanin A, 5-OMe-genistein, 7
      OMe-genistein, irisolidone and formononetin slightly induce transcription with
      hER beta, they act as antagonists in the induction of transcription by 17beta
      estradiol. The results show that methylation or glucosidation of isoflavones
      generally inhibits their phytoestrogenic activities.

PMID- 11824556
TI  - Ixeris dentata green sap inhibits both compound 48/80-induced aanaphylaxis-like
      response and IgE-mediated anaphylactic response in murine model.
AB  - We studied the inhibitory effect of the green sap of Ixeris dentata (IXD) on
      compound 48/80-induced anaphylaxis-like response in a murine model. IXD dose
      dependently inhibited the anaphylaxis-like response induced by compound 48/80 in
      mice. IXD inhibited the anaphylaxis-like fatal response at the dose of 0.1 g/kg
      by 75%. IXD had a significant inhibitory effect on compound 48/80-induced ear
      swelling response at the doses of 0.05 and 0.1 g/kg. IXD (0.1 g/kg) also
      inhibited passive cutaneous anaphylaxis mediated by anti-dinitrophenyl IgE by
      81.45%. When IXD was given as a pretreatment at concentrations ranging from 0.005
      to 0.1 g/l, the histamine release from rat peritoneal mast cells induced by
      compound 48/80 was reduced in a dose-dependent manner. These results indicate
      that IXD may possess antianaphylactic activity.

PMID- 11824557
TI  - Induction and inhibition of cytochrome P450 and drug-metabolizing enzymes by
      climbazole.
AB  - To determine the effect of climbazole on hepatic microsomal cytochrome P450
      (P450) and drug-metabolizing enzymes, four different P450 isoforms (CYP2B1, 3A2,
      2E1, and 2C12) were examined in female Long-Evans rats. Treatment of rats with
      climbazole resulted in the induction of P450 content. Climbazole both induced and
      inhibited aminopyrine N-demethylase activity, but not erythromycin N-demethylase
      activity. Uridine 5'-phosphate (UDP)-glucuronosyl transferase and glutathione S
      transferase activities were also increased with climbazole treatment. Immunoblot
      analyses revealed that climbazole induces CYP2B1 and CYP3A2 at the lower dose
      examined, but it failed to increase CYP2B1 at the higher dose. Northern blot
      analysis revealed that climbazole markedly increases P450 2B1 mRNA. These results
      indicate that climbazole induces and inhibits P450-dependent drug-metabolizing
      enzymes in vivo and may have the dose-differential effect on CYP2B1 in rat liver.

PMID- 11824558
TI  - Metabolism of 20(S)- and 20(R)-ginsenoside Rg3 by human intestinal bacteria and
      its relation to in vitro biological activities.
AB  - When ginsenoside Rg3 was anaerobically incubated with human fecal microflora, all
      specimens metabolized ginsenoside Rg3 to ginsenoside Rh2 and protopanaxadiol. The
      main metabolite was ginsenoside Rh2. 20(S)-ginsenoside Rg3 was quickly
      transformed to 20(S)-ginsenoside Rh2 or 20(S)-protopanaxadiol in an amount 19
      fold that compared with the transformation of 20(R)-ginsenoside Rg3 to 20(R)
      ginsenoside Rh2 or 20(R)-protopanaxadiol. Among the bacteria isolated from human
      fecal microflora, Bacteroides sp., Eubacterium sp., and Bifidobacterium sp.
      metabolized ginsenoside Rg3 to protopanaxadiol via ginsenoside Rh2. However,
      Fusobacterium sp. metabolized ginsenoside Rg3 to ginsenoside Rh2 alone. Among
      ginsenoside Rg3 and its metabolites, 20(S)-protopanaxadiol and 20(S)-ginsenoside
      Rh2 exhibited the most potent cytotoxicity against tumor cell lines, 20(S)- and
      20(R)-protopanaxadiols potently inhibited the growth of Helicobacter pylori, and
      20(S)-ginsenoside Rh2 inhibited H+/K+ ATPase of rat stomach.

PMID- 11824559
TI  - Comparative study of the high molecular mass fraction and low molecular mass
      fraction of Sho-saiko-to in a murine immunologically induced liver injury model.
AB  - We compared the pharmacological actions of the high and low molecular mass
      fractions of Sho-saiko-to using a murine immunologically induced liver injury
      model to estimate the roles of these fractions in the expression of the
      pharmacological action. In a Bacillus Calmette-Guerin (BCG)/lipopolysaccharide
      (LPS)-induced liver injury model, Sho-saiko-to and both of its fractions
      significantly reduced the increases in the aminotranseferase levels in serum.
      They also reduced the increase in the nitric oxide (NOx) level in serum. On the
      other hand, Sho-saiko-to and its high molecular mass fraction suppressed the
      increase in plasma NOx level in an LPS-induced endotoxin shock model but its low
      molecular mass fraction did not. These results suggest the possibility that both
      fractions act hepatoprotectively in a different manner. We believe that these
      results can help to elucidate the mechanism of action of ingredients in Sho-saiko
      to.

PMID- 11824560
TI  - Metabolism of kalopanaxsaponin K by human intestinal bacteria and antirheumatoid
      arthritis activity of their metabolites.
AB  - When kalopanaxsaponin K (KPK) from Kalopanax pictus was incubated for 24 h at 37
      degrees C with human intestinal microflora, KPK was mainly metabolized to
      kalopanaxsaponin I (KPI) via kalopanaxsaponin H (KPH) rather than via
      kalopanaxsaponin J (KPJ), and then transformed to kalopanaxsaponin A (KPA) and
      hederagenin. Bacteroides sp., and Bifidobacterium sp. and Fusobacterium sp.
      transformed KPK to KPI and KPA and hederagenin via KPH or KPJ. However,
      Lactobacillus sp. and Streptococcus sp. transformed KPK to KPI, KPA, and
      hederagenin only via KPJ. The metabolite KPA of KPK showed potent antirheumatoid
      arthritis activity.

PMID- 11824561
TI  - Hepatoprotective and antioxidative properties of Salacia reticulata: preventive
      effects of phenolic constituents on CCl4-induced liver injury in mice.
AB  - The hepatoprotective effects of the hot water (SRHW) and methanolic (SRM)
      extracts from the roots and stems of Salacia reticulata were examined using an
      oxidative stress-induced liver injury model. Both SRHW and SRM extracts (400
      mg/kg, p.o.) significantly suppressed the increase in glutamic oxaloacetic
      transaminase (GOT) and glutamic pyruvic transaminase (GPT) activities in carbon
      tetrachloride (CCl4)-treated mice. These extracts also inhibited CCl4-induced
      thiobarbituric acid-reactive substance (TBA-RS) formation, which indicates
      increased lipid peroxidation in the liver. A good correlation (r=0.945, p<0.01)
      was observed between the amount of phenolic compounds in the extracts and their
      inhibitions of TBA-RS formation. The IC50 values of the extracts on 1,1-diphenyl
      2-picrylhydrazyl (DPPH) radical scavenging were less than 10 microg/ml and the
      antioxidative activities of six phenolic compounds from the roots of S.
      reticulata were examined. Mangiferin, (-)-4'-O-methylepigallocatechin, and (-)
      epicatechin-(4beta-->8)-(-)-4'-O-methylepigallocatechin, which a principal
      phenolic compounds, showed potent scavenging activity on DPPH radicals and their
      concentrations required for 50% reduction of 40 microM DPPH radicals were 5.9,
      10, and 3.2 microM, respectively. On the other hand, against the CCl4-induced
      serum GOT and GPT elevations and TBA-RS formation in mice, mangiferin and (-)-4'
      O-methylepigallocatechin showed potent activity at a dose of 100 mg/kg, but (-)
      epicatechin-(4beta-->8)-(-)-4'-O-methylepigallocatechin did not. These results
      suggest that the antioxidative activity of the principal phenolic compounds is
      involved in the hepatoprotective activity of S. reticulata.

PMID- 11824563
TI  - Dehydrotrametenolic acid induces preadipocyte differentiation and sensitizes
      animal models of noninsulin-dependent diabetes mellitus to insulin.
AB  - We recently discovered that the triterpene acid compound dehydrotrametenolic acid
      promotes adipocyte differentiation in vitro and acts as an insulin sensitizer in
      vivo. This natural product has been isolated from dried sclerotia of Poria cocos
      WOLF (Polyporaceae), a well-known traditional Chinese medicinal plant. We
      examined the effects of dehydrotrametenolic acid on plasma glucose concentration
      in obese hyperglycemic db/db mice. Dehydrotrametenolic acid can reduce
      hyperglycemia in mouse models of noninsulin-dependent diabetes mellitus (NIDDM)
      and act as an insulin sensitizer as indicated by the results of the glucose
      tolerance test. These terpenoids and thiazolidine type of antidiabetic agents
      such as Ciglitazone, although structurally unrelated, share many biological
      activities: both induce adipose conversion, activate peroxisome proliferator
      activated receptor gamma (PPAR gamma) in vitro, and reduce hyperglycemia in
      animal models of NIDDM. Dehydrotrametenolic acid is a promising candidate for a
      new type of insulin-sensitizing drug. This finding is very important for the
      development of insulin sensitizers that are not of the thiazolidine type.

PMID- 11824562
TI  - Effect of Astragali radix extract on lipopolysaccharide-induced inflammation in
      human amnion.
AB  - The effects of Astragali radix extract on interleukin (IL)-6 and tumor necrosis
      factor (TNF)-alpha productions, prostaglandin E2 (PGE2) biosynthesis, and
      leukotriene C4 (LTC4) production from lipopolysaccharide (LPS)-stimulated human
      amnion cells were investigated. Amnion cells produced detectable amounts of both
      IL-6 and TNF-alpha under LPS-stimulated conditions. Astragalus extract inhibited
      the production of IL-6. However, TNF-alpha production was not inhibited by the
      extract on L929 cytotoxicity assay. Treatment of amnion cells with LPS for up to
      24 h resulted in an increase in PGE2 release in a concentration- and time
      dependent manner. The extract (150 mg/ml) significantly inhibited the output of
      PGE2 by amnion cells (p<0.01). The arachidonate lipoxygenase metabolite (LTC4)
      was increased by LPS treatment of amnion cells. Astragalus extract (30 mg/ml)
      inhibited LTC4 production by approximately 65% throughout the culture period.
      These results suggest that Astragali radix extract may have a role in inhibiting
      bacterial infection-associated preterm labor by suppressing the productions of IL
      6, PGE2, and LTC4 by human amnion cells.

PMID- 11824564
TI  - Influence of honey on the gastrointestinal metabolism and disposition of
      glycyrrhizin and glycyrrhetic acid in rabbits.
AB  - To investigate the effects of honey on the pharmacokinetics of glycyrrhizin and
      glycyrrhetic acid, administration of glycyrrhizin or glycyrrhetic acid with and
      without honey was carried out in rabbits in a randomized crossover design. An in
      vitro study using rabbit fecal flora was employed to elucidate the mechanism of
      the interaction. HPLC methods were used for the determination of glycyrrhizin,
      glycyrrhetic acid and 3-dehydroglycyrrhetic acid concentrations in serum and
      feces. Paired and unpaired Student's t-tests were used for statistical
      comparisons for in vivo and in vitro studies, respectively. Our study indicated
      that the area under the curve (AUC0-t) of glycyrrhetic acid was significantly
      enhanced by 53% when honey was concomitantly given with glycyrrhizin, whereas
      that of glycyrrhizin was not significantly altered. Nevertheless, lack of effect
      was observed when honey was concurrently given with glycyrrhetic acid. Fecal
      study indicated that both the hydrolysis of glycyrrhizin to glycyrrhetic acid and
      subsequent oxidation of glycyrrhetic acid to 3-dehydroglycyrrhetic acid were
      significantly affected in the presence of honey to result in more glycyrrhetic
      acid available for absorption. It could be concluded that honey significantly
      affected the gastrointestinal metabolism of glycyrrhizin and resulted in the
      increased glycyrrhetic acid exposure. Therefore, honey might enhance the efficacy
      and adverse effects of glycyrrhizin.

PMID- 11824565
TI  - Pharmaceutical and clinical assessment of hydroquinone ointment prepared by
      extemporaneous nonsterile compounding.
AB  - Ointments of the skin depigmentation agent hydroquinone (HQ) have been prepared
      by extemporaneous nonsterile compounding in Japan by imitating skin lightening
      creams commercially available in the U.S.A. and European Union. In our hospital,
      HQ ointments consisting of 5 or 10% HQ, 1.6% L(+)-ascorbic acid (AsA), 0.5% (w/w)
      Na2SO3, 10% (v/w) glycerin and hydrophilic ointment have been prepared. However,
      various problems have been observed including chromatic aberration of HQ
      ointments, relatively large variability of efficacy, and undesirable side effects
      although they were mild. Herein, the pharmaceutical and clinical properties of
      the HQ ointments were evaluated. HQ ointments were highly effective for treatment
      of various types of skin pigmentation. Chromatic aberration occurred during 3
      months of storage, but this could be suppressed by storage at 4 degrees C.
      Chromatic aberration was independent of prescribed HQ content, and was not
      explained by alterations of HQ or p-benzoquinone (p-BQ) contents. Unexpectedly,
      removal of both antioxidants resulted in suppression of chromatic aberration, but
      an increase in p-BQ content. Acidification by removal of Na2SO3 only was further
      effective for the suppression of chromatic aberration, but with a decrease of p
      BQ content except in the initial period. Chromatic aberration was due to water
      soluble material and insoluble material both formed by co-existence of HQ and p
      BQ at a molecular ratio of 5:3 to 1:1. 1H-NMR analysis elucidated that the water
      soluble material was not HQ or p-BQ, and the insoluble material was a complex of
      HQ and p-BQ with non-covalent binding.

PMID- 11824566
TI  - Reconsideration of drug release from temperature-sensitive liposomes.
AB  - The liposomal phase transition temperature was monitored in unstirred suspensions
      using a differential scanning calorimeter. The main and pre-transition
      temperatures under conditions of stirring were measured by the change in 90
      degrees light scattering using a fluorescence spectrophotometer. Both methods
      show the same main transition temperature either with or without stirring.
      Temperature sensitive liposomes were made of DPPC
      (dipalmitoylphosphatidylcholine), DMPC (dimylisitoylphosphatidylcholine) or DSPC
      (distearoylphosphatidylcholine). The calcein release profile from the liposomes
      depends on the stirring time of the liposome suspension at the main transition
      temperature. For 1 h incubation, the leakage profile with and without stirring is
      similar. It had been hypothesized that temperature sensitive liposomes released
      drug at the main-transition temperature. However, calcein leakage from liposomes
      is observed also at the pre-transition temperature. Thus, a liposomal
      encapsulated drug will likely leak from DPPC liposomes at body temperature (37
      degrees C), even if the liposomes were designed to have a higher main transition
      temperature.

PMID- 11824568
TI  - Novel 5-substituted-1H-tetrazole derivatives as potent glucose and lipid lowering
      agents.
AB  - A series of 5-(4-alkoxyphenylalkyl)-1H-tetrazole derivatives, containing an
      oxazole-based group at the alkoxy moiety, was prepared and their antidiabetic
      effects were evaluated in two genetically obese and diabetic animal models, KKAy
      mice and Wistar fatty rats. Syntheses were performed by cyclization of the
      corresponding nitrites reacting with azide compounds. A large number of the 5-(4
      alkoxyphenylalkyl)-1H-tetrazoles showed potent glucose and lipid lowering
      activities in KKAy mice. In particular, 5-[3-[6-(5-methyl-2-phenyl-4-oxazolyl
      methoxy)-3-pyridyl]propyl]-1H-tetrazole had potent glucose lowering activity
      (ED25=0.0839 mg x kg(-1) x d(-1)), being 72 times more active than pioglitazone
      hydrochloride (ED25=6.0 mg x kg(-1) x d(-1)). This compound also showed strong
      glucose lowering (ED25=0.0873 mg x kg(-1) x d(-1)) and lipid lowering effects
      (ED25=0.0277 mg x kg(-1) x d(-1)) in Wistar fatty rats. The antidiabetic effects
      of this compound are considered to be due to its potent agonistic activity for
      peroxisome proliferator-activated receptor gamma (PPARgamma) (EC50 = 6.75 nM).

PMID- 11824567
TI  - Pd asymmetric allylic alkylation (AAA). A powerful synthetic tool.
AB  - Palladium catalyzed asymmetric allylic alkylations represent a challenging
      problem because the mechanism of the reaction places the chiral environment
      distal to the bond breaking or making events responsible for the asymmetric
      induction. Furthermore, unlike virtually every other asymmetric process, many
      strategies can be employed for introduction of asymmetry and many different types
      of bonds can be formed. While over 100 different ligands have been designed, a
      family of ligands derived from 2-diphenylphosphinobenzoic or 1-naphthoic acid and
      chiral scalemic diamines have been successful in inducing excellent
      enantioselectivity by five different enantiodiscriminating events. These methods
      have already provided practical strategies towards numerous biological targets-
      some of which are adenosine and its enantiomer, aflatoxin B, aristeromycin,
      calanolide A and B, carbovir, cyclophellitol, ethambutol, galanthamine,
      mannostatin, neplanocin, phyllanthocin, sphingofungins E and F, tetraponaines,
      vigabatrin, and valienamine.

PMID- 11824569
TI  - Alpha-glucosidase inhibitory constituents from Cuscuta reflexa.
AB  - Two new compounds, 7'-(3',4'-dihydroxyphenyl)-N-[(4
      methoxyphenyl)ethyl]propenamide (4), and 7'-(4'-hydroxy,3'-methoxyphenyl)-N-[(4
      butylphenyl)ethyl]propenamide (5) have been isolated from Cuscuta reflexa along
      with five known compounds, 6,7-dimethoxy-2H-1-benzopyran-2-one (1), 3-(3,4
      dihydroxyphenyl)-2-propen-1-ethanoate (2), 6,7,8-trimethoxy-2H-1-benzopyran-2-one
      (3), 3-(4-O-beta-D-glucopyranoside-3,5-dimethoxyphenyl)-2-propen-1-ol (6), 2-(3
      hydroxy-4-methoxyphenyl)-3,5-dihydroxy-7-O-beta-D-glucopyranoside-4H-1
      benzopyrane-4-one (7), reported for the first time from this species. Structures
      of these compounds were determined by spectral analysis. These compounds showed
      strong inhibitory activity against alpha-glucosidase.

PMID- 11824572
TI  - Cycloartane glycosides from the rhizomes of Cimicifuga racemosa and their
      cytotoxic activities.
AB  - Phytochemical analysis of the rhizomes of Cimicifuga racemosa (Ranunculaceae)
      resulted in the isolation of twelve cycloartane glycosides (1--12), including
      four new ones (4--6, 12). The structures of the new compounds were determined by
      spectroscopic analysis, including two-dimensional (2D) NMR data, and chemical
      methods. The isolated compounds were evaluated for their cytotoxic activities
      against human oral squamous cell carcinoma (HSC-2) cells and normal human
      gingival fibroblasts (HGF).

PMID- 11824571
TI  - Isolation and structure elucidation of a new prenylcoumarin from Murraya
      paniculata var. omphalocarpa (Rutaceae).
AB  - A new C-8 prenylated 5,7-dimethoxycoumarin named omphamurrayin was isolated from
      the leaves of Murraya paniculata var. omphalocarpa, and its structure was
      established as 5,7-dimethoxy-8-(1-oxo-2-senecioyl-3-methyl-3-butenyl)-2H-1
      benzopyran-2-one on the basis of the spectroscopic evidence. The taxonomic status
      of M. paniculata var. omphalocarpa is briefly discussed, along with its
      synonymity to M. paniculata from the chemosystematic viewpoint.

PMID- 11824570
TI  - Chemical constituents from the colombian medicinal plant Niphogeton ternata.
AB  - Two coumarins and one polyacetylene, 5-0-(3-chloro-2-hydroxy-3-methylbutyl)-8
      methoxypsoralen (1), 2',3'-dihydro-jatamansin (2), and 10-chloro-1-heptadecene
      4,6-diyne-3,8,9-triol (3), along with 15 known compounds (4-18), were isolated
      from the methanol extract of Niphogeton ternata. Their structures were elucidated
      by spectroscopy.

PMID- 11824573
TI  - Absolute structure of panaxytriol.
AB  - Diastereomeric mixture at C-3 of (9R,10R)-panaxytriol acetonide (3) and (9S,10S)
      panaxytriol acetonide (4) were enantioselectively acetylated to give (3R)
      acetates (3a-Ac, 4a-Ac) and (3S)-alcohols (3b, 4b) by enzyme mediated-acetylation
      using CHIRAZYME and vinyl acetate, respectively. Hydrolysis of (3R)-acetate (3a
      Ac, 4a-Ac) with CHIRAZYME and phosphate buffer afforded (3R)-alcohols (3a, 4a),
      respectively. Deprotection of panaxytriol acetonides (3a, 3b, 4a, 4b) gave
      panaxatriol and its isomers, respectively. Comparison of optical rotation values
      of the synthetic panaxatriols with that of the natural one confirmed that the
      absolute configuration of panaxytriol sould be 3R,9R,10R.

PMID- 11824574
TI  - Synthesis of N-[2-(1-piperidinyl)ethyl]benzamides.
AB  - Novel benzamide derivatives, N-[1-(aminocarbonyl)-2-(1
      piperidinyl)ethyl]benzamides (4 and 5), were prepared from the reaction of beta
      piperidinoalanine (6) as the starting material.

PMID- 11824576
TI  - Biflavanones, diterpenes, and coumarins from the roots of Stellera chamaejasme L.
AB  - A new biflavanone (1) with a C-3/C-3" linkage, a new daphnane-type diterpene (2)
      acylated by an unsaturated fatty acid, and a new coumarin glycoside (3), along
      with six lignans, two phenylpropanoids, five flavonoids, two diterpenes, and
      three coumarins were isolated from the roots of Stellera chamaejasme L.
      (Thymelaeaceae). Elucidation of these secondary metabolites of S. chamaejasme L.
      supplied strong chemical verification of the close taxonomic relationships among
      the genera Stellera, Daphne, and Wikstroemia, all of which belong to the family
      Thymelaeaceae.

PMID- 11824575
TI  - Brine shrimp lethality test active constituents and new highly oxygenated seco
      prezizaane-type sesquiterpenes from Illicium merrillianum.
AB  - In the study of bioactive substances in Illicium plants, the methanol extract of
      I. merrillianum showed brine shrimp lethality test (BST) activity at 200
      microg/ml. Bioassay-guided fractionation of the BST active fractions resulted in
      the isolation of 4-O-methyleudesm-11-en-4alpha-ol, eudesmol-11-en-4alpha-ol and (
      )-hinokinin as potent BST active compounds. On the other hand, four new highly
      oxygenated seco-prezizaane-type sesquiterpenes, merrilliortholactone (1), 2alpha
      hydroxycycloparvifloralone (2), 2alpha-hydroxycycloparviflorolide (3), and 2alpha
      hydroxyanisatin (4) were isolated from the BST-inactive polar fractions. The
      structures of new compounds were elucidated by extensive analyses of spectral
      data. Furthermore, the absolute configuration of 3 was established by the
      modified Mosher's method. Compounds 1--4 showed neither BST activity at 100
      microg/ml nor neurite outgrowth-promoting activity.

PMID- 11824577
TI  - Acylation of hydrazides with acetic acid and formic acid.
AB  - In peptide synthesis, hydrazides are important intermediates for the azide
      coupling method. A hydrazide is converted to the corresponding azide in the
      presence of an acid and a nitrite. When acetic acid (or formic acid) is used as
      the acid, partial acetylation (or formylation) of the hydrazide occurs as a side
      reaction. Formylation of the hydrazide is much faster than acetylation. Removal
      of the formyl group on the hydrazide with hydrazine and hydroxylamine was
      studied. The rate of deformylation with hydrazine treatment is faster than that
      with hydroxylamine treatment.

PMID- 11824578
TI  - A concise synthesis of furostifoline by tetrabutylammonium fluoride-promoted
      indole ring formation.
AB  - Furostifoline, a furo[3,2-a]carbazole alkaloid, was synthesized in 10% overall
      yield in four steps from 2-acetyl-3-bromofuran. The key step of this synthesis
      was the 2-substituted indole formation with tetrabutylammonium fluoride (TBAF)
      from 2-(2-propenyl)-3-((2-ethoxycarbonylamino)phenylethynyl)furan, which was
      easily prepared from ethyl 2-ethynylphenylcarbamate with 3-bromo-2-(2
      propenyl)furan by the Sonogashira reaction.

PMID- 11824579
TI  - Synthesis and pharmacological evaluation of new 16-methyl pregnane derivatives.
AB  - The pharmacological activity of several new pregnane derivatives 15-19 were
      determined on gonadectomized male hamster flank organs, seminal vesicles and in
      vitro conversion of testosterone (T) to dihydrotestosterone (DHT) as 5alpha
      reductase inhibitors. Steroids 15-19 decreased the diameter of the pigmented spot
      in the flank organs as compared to the T treated animals; in this model, steroids
      16 and 19 showed a higher activity than the commercially available finasteride 3.
      Injection of T increased the weight of the seminal vesicles. Compounds 15-19 when
      injected together with T decreased the weight of the seminal vesicles thus
      showing an antiandrogenic effect. The trienone 19 exhibited a considerably higher
      activity than finasteride. Steroids 15-19 inhibited the in vitro metabolism of
      [3H]T to [3H]DHT in seminal vesicles homogenates of gonadectomized male hamsters.
      Compounds 18 and 19 showed a much higher antiandrogenic effect than finasteride.
      This enhancement of the biological activity could probably be attributed to the
      coplanarity of the steroidal skeleton as previously observed by our group. The
      high antiandrogenic activity of the epoxy compound 16 is probably the result of
      the ring opening of the oxiran ring with the nucleophilic part of the enzyme
      5alpha-reductase thus leading to a stable adduct with concomitant deactivation of
      this enzyme.

PMID- 11824580
TI  - Solubility prediction of anthracene in mixed solvents using a minimum number of
      experimental data.
AB  - Numerical methods to predict the solubility of anthracene in mixed solvents have
      been proposed. A minimum number of 3 solubility data points in sub-binary
      solvents has been employed to calculate the solvent-solute interaction terms of a
      well established colsolvency model, i.e. the combined nearly ideal binary
      solvent/Redlich-Kister model. The calculated interaction terms were used to
      predict the solubility in binary and ternary solvent systems. The predicted
      solubilities have been compared with experimental solubility data and the
      absolute percentage mean deviation (APMD) has been computed as a criterion of
      prediction capability. The overall APMD for 25 anthracene data sets in binary
      solvents is 0.40%. In order to provide a predictive method, which is based fully
      on theoretical calculations, the quantitative relationships between sub-binary
      interaction terms and physicochemical properties of the solvents have been
      presented. The overall APMD value for 41 binary data sets is 9.19%. The estimated
      binary interaction terms using a minimum number of data points and the
      quantitative relationships have then been used to predict anthracene solubility
      data in 30 ternary solvent systems. The produced APMD values are 3.72 and 15.79%,
      respectively. To provide an accurate correlation for solubility in ternary
      solvent systems, an extension to the combined nearly ideal multicomponenet
      solvent/Redlich-Kister (CNIMS/R-K) model was proposed and the corresponding
      overall AMPD is 0.38%.

PMID- 11824581
TI  - Measurement of physical strength of pharmaceutical extruded pellets.
AB  - This paper describes a novel and simple method for measuring the physical
      strength of pharmaceutical pellets prepared by extrusion granulation.
      Pharmaceutical powders composed of lactose, cornstarch, and microcrystalline
      cellulose were kneaded with purified water and dry binder
      (hydroxypropylcellulose), then extruded through a dome-type extrusion granulator.
      The physical strength of the dried extruded pellets was measured with a novel
      system: pellets and grinding alumina media were both fed into a ball mill pot and
      then "grinding degree" was measured as defined by the ground fine powder fraction
      after being rotated in the pot. The grinding conditions such as grinding time and
      number of alumina balls were optimized. The measured physical strength and pellet
      strength measured with a typical strength tester was compared. Quantitative
      relationships between the strength and the physical properties of the pellets
      such as friability and disintegration time were also investigated. It was found
      that the newly developed system could easily and accurately evaluate the physical
      strength of extruded pellets and could also predict the various physical
      properties.

PMID- 11824582
TI  - Synthesis of N1-phenethyl substituted indole derivatives as new melatoninergic
      agonists and antagonists.
AB  - The potency of new indolic N1-phenethyl substituted melatoninergic ligands with
      and without methyl groups in the alpha and beta position of the alkanamidoethyl
      side chain was examined using the pigment aggregation response in a clonal line
      of Xenopus laevis melanophores. The non 5-OMe substituted compounds, 8a--e, are
      all weak antagonists while introduction of the 5-OMe group, 9a--e, increases both
      agonist and antagonist activity except for 9c (R=C3H7), which is only an agonist
      and 9e (R=c-C4H7), which is only an antagonist. Introduction of an alpha-methyl
      group into the 5-OMe derivatives, 14a-e, reduces the agonist potency while
      introduction of a beta-methyl group has only a small effect on either the agonist
      or antagonist potency. Double beta-methyl substitution of the 5-OMe derivatives,
      20a--e, generally increases the agonist potential (20c, R=C3H7 is the most potent
      agonist of the compounds described) and decreases the antagonist potency, except
      for 20a (R=CH3), which is the most potent antagonist of this series of compounds.

PMID- 11824584
TI  - A new nonpeptide tachykinin NK1 receptor antagonist isolated from the plants of
      Compositae.
AB  - To find new tachykinin NK1 receptor antagonists from natural sources, we examined
      the tachykinin antagonist activity in the extracts of approximately 200 species
      of plants by the use of isolated guinea pig ileum. As a result, we discovered a
      novel and potent NK1 receptor antagonist in the extract of dried flowers of
      Matricaria chamomilla L. (chamomile). The structure of the antagonist was
      established as N1,N5,N10,N14-tetrakis[3-(4-hydroxyphenyl)-2-propenoyl]-1,5,10,14
      tetraazatetradecane (tetracoumaroyl spermine, 1a). The Ki values of 1a, estimated
      from the inhibitory action on the substance P (SP)-induced contraction of the
      guinea pig ileum and the inhibition of the binding of [3H][Sar9, Met(O2)11]SP to
      human NK1 receptors, were 21.9 nM and 3.3 nM, respectively. 1a is the first
      potent NK1 receptor antagonist from natural sources and it has a unique structure
      of a polyacylated spermine. 1a was concentrated in pollen of Matricaria
      chamomilla L. and was also found in the extracts of flowers of other four species
      of Compositae. In addition, we found N1,N5,N10-tris[3-(4-hydroxyphenyl)-2
      propenoyl]-1,5,10,14-tetraazatetradecane (2) as a new compound in the extract of
      flowers of Matricaria chamomilla L., which did not exhibit any tachykinin
      antagonist activity. A number of related compounds were synthesized, and the
      structure-activity relationship was studied.

PMID- 11824583
TI  - Use of beta-cyclodextrins to prevent modifications of the properties of carbopol
      hydrogels due to carbopol-drug interactions.
AB  - Carbomers are carboxyvinylic derivatives that are widely used in the manufacture
      of hydrogel dosage forms. Because of their anionic nature and large number of
      acid groups, they tend to interact with cationic substances, and with other
      hydrophilic polymers containing alcohol groups. Here, we report a study of
      interactions between the carbomer Carbopol and the cationic drug propranolol
      hydrochloride in the solid state and in solution, and of the effects of such
      interactions on the properties of the hydrogel. We found that the drug forms an
      insoluble ionic complex with the polymer, modifying all of the hydrogel
      properties studied (swelling, release, bioadhesion). The inclusion of beta
      cyclodextrin in the formulation reduces polymer/drug interactions, so that
      hydrogel properties remain unchanged. This is probably attributable to formation
      of inclusion complexes of beta-cyclodextrin and the drug, so that the drug is
      prevented from interacting with the polymer.

PMID- 11824585
TI  - Syntheses of (4,1-benzoxazepine-3-ylidene)acetic acid derivatives and their
      inhibition of squalene synthase.
AB  - The (3,5-trans)-7-chloro-5-(2-chlorophenyl)-2-oxo-1,2,3,5-tetrahydro-4,1
      benzoxazepine-3-acetic acid derivatives 1 have been previously identified as
      potent squalene synthase inhibitors. A series of (4,1-benzoxazepin-3
      ylidene)acetic acid derivatives were synthesized and evaluated for their
      inhibition of rat and human squalene synthase, and the (E)-isomers were found to
      exhibit potent inhibitory activity, with the same potency as 4,1-benzoxazepine-3
      acetic acid derivatives. In contrast the (Z)-isomers did not exhibit significant
      inhibitory activity, and the active conformation of the 4,1-benzoxazepine-3
      acetic acid derivatives was deduced from the folded conformation of the (E)
      isomers.

PMID- 11824586
TI  - Microbial enantioselective ester hydrolysis for the preparation of optically
      active 4,1-benzoxazepine-3-acetic acid derivatives as squalene synthase
      inhibitors.
AB  - Microbial enantioselective ester hydrolysis for the preparation of optically
      active (3R,5S)-(-)-5-phenyl-4,1-benzoxazepine-3-acetic acid derivatives as potent
      squalene synthase inhibitors was investigated. Pseudomonas diminuta and
      Pseudomonas taetrolens hydrolyzed the racemic ethyl ester of the 5-(2
      chlorophenyl) analogue to yield the (-)-carboxylic acid with excellent
      enantiomeric excess (>99% ee). We found that the (-)-enantiomer was an active
      inhibitor. Bulkiness of the ester moiety did not affect the enantioselectivity
      but did affect reactivity. The racemic ethyl ester of the 5-(2-methoxyphenyl)
      analogue, 5-(2,3-dimethoxyphenyl) analogue and 5-(2,4-dimethoxyphenyl) analogue
      were also hydrolyzed with Pseudomonas taetrolens to afford enantiomerically pure
      (-)-carboxylic acids in large scale. As another route to (3R,5S)-(-)-7-chloro-5
      (2,3-dimethoxyphenyl)-1-neopentyl-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepine-3
      acetic acid [(-)-1c], the earlier intermediate (-)-2-amino-5-chloro-alpha-(2,3
      dimethoxyphenyl)benzyl alcohol [(-)-12] was successfully obtained by asymmetric
      hydrolysis of (+/-)-5-chloro-alpha-(2,3-dimethoxyphenyl)-2-pivaloylaminobenzyl
      acetate with Pseudomonas sp. S-13 with >99% ee in kilogram scale followed by
      alkaline treatment. The product (-)-12 was converted to (-)-1c without
      racemization.

PMID- 11824587
TI  - Water-soluble constituents of caraway: carvone derivatives and their glucosides.
AB  - Nine monoterpenoids related to carvone and seven glucosides were isolated from
      the water-soluble portion of the methanolic extract of the caraway (fruit of
      Carum carvi L.), and their structures were clarified by spectral investigation.
      Among them, eight monoterpenoids and six glucosides were new.

PMID- 11824588
TI  - Constituents of the underground parts of Glehnia littoralis.
AB  - From the underground parts of Glehnia littoralis FR. Schmidt ex Miquel
      (Umbelliferae), 26 compounds, including two new lignan glycosides [giehlinosides
      A (1) and B (2)], a new neolignan glycoside [glehlinoside C (3)], and a new
      phenylpropanoid glycoside 14-[beta-D-apiofuranosyl-(1-->6)-beta-D
      glucopyranosyloxyl-3-methoxypropiophenone (4)1, were obtained and their
      structures were determined by analysis of their spectral data. The 1,1-diphenyl-2
      picrylhydrazyl radical-scavenging assay disclosed quercetin (8), isoquercetin
      (9), rutin (10), chlorogenic acid (11), and caffeic acid (24) as the major
      antioxidative constituents in this crude drug.

PMID- 11824589
TI  - PH-dependent coordination of metal-lisinopril complex investigated by attenuated
      total reflection/Fourier transform infrared spectroscopy.
AB  - In order to simulate the in vivo binding behavior of angiotensin-converting
      enzyme (ACE) inhibitors to the zinc-containing active center of ACE, the in vitro
      interaction between lisinopril and zinc or nickel ions was investigated in
      aqueous solutions of different pH by using attenuated total reflection
      (ATR)/Fourier transform infrared (FT-IR) spectroscopy with second-derivative IR
      spectral analysis. The results indicated that the lisinopril dissociation process
      occurred in a stepwise fashion during increase in pH. The IR peaks at 1642 cm(-1)
      (carbonyl stretching of tertiary amide) and at 1582 cm(-1) (asymmetric COO-
      stretching) for lisinopril in solution at pH 3.5 shifted to 1606 and 1586 cm(-1)
      after addition of Ni2+ ions, respectively, but there was no marked changes in IR
      spectra of lisinopril after addition of Zn2+ ions. When the Zn2+ ions were added
      to lisinopril solution at pH 5.0, the peak at 1642 cm(-1) also shifted to 1604
      cm(-1) and the peak at 1582 cm(-1) shifted to 1586 cm(-1), similar to the changes
      at pH 3.5 after adding Ni2+ ions. However, the peaks at 1582 and 1642 cm(-1) both
      shifted to 1599 cm(-1) after addition of Ni2+ ions at pH 5.0 or at pH 7.3. The
      peak at 1576 cm(-1) also shifted to 1599 cm(-1) after addition of Zn2+ ions to
      lisinopril solution at pH 7.3. Different coordination sites or types (chelating,
      bridging or pseudounidentate complex) between lisinopril and Zn2+ or Ni2+ ions
      were proposed, based on the separation value between v(as) (COO-) and v(s) (COO
      ), and the shifting of carbonyl groups. Coordination of the secondary amine in
      lisinopril to metal ions was also evidenced.

PMID- 11824590
TI  - Reactions of oxalyl chloride with 1,2-cycloalkanediols in the presence of
      triethylamine.
AB  - The relationship between the product patterns and the configurations of 1,2
      cycloheptane- and 1,2-cyclooctanediols 9 in the cyclocondensations with oxalyl
      chloride in the presence of triethylamine at 0 degrees C has been shown analogous
      to that obtained for 1,2-disubstituted acyclic ethylene glycols 1: cis-1,2
      cyclooctanediol (9f) produced the cyclic oxalate 14f as the major product, while
      trans-1,2-cycloheptanediol (9e) and trans-1,2-cyclooctanediol (9g) formed the
      cyclic carbonates 12e, g as the major products. On the other hand, the cyclic
      oxalates 14a-d were formed as the major products from 1,2-cyclopentane- and 1,2
      cyclohexanediols regardless of the configuration. These results can be accounted
      for by assuming the boat-like transition states for cyclizations of the half
      esters of comparatively rigid five- and six-membered diols 9a--d. The cyclic
      oxalates 14a, c may be directly formed through the resulting tetrahedral
      intermediates from cis-diols (9a,c), and the cyclic carbonates 12a,c as the minor
      products after ring inversion of the tetrahedral intermediates. The tetrahedral
      intermediates from the trans-isomers 9b, d cannot undergo ring inversion,
      producing no traces of the cyclic carbonates 12b, d.

PMID- 11824591
TI  - Formulation development of a filter-sterilizable lipid emulsion for lipophilic KW
      3902, a newly synthesized adenosine A1-receptor antagonist.
AB  - KW-3902 (a newly synthesized adenosine A1-receptor antagonist) has potent
      diuretic and renal protective activities. The objective of the present study was
      to develop an injectable formulation of KW-3902, that was water-insoluble and
      less than 1 microg/ml, and so lipid emulsion was selected as a favorable
      formulation. Changing the mixing ratio of oil to lecithin, the particle size of
      the lipid emulsion was controlled, and by adjusting the mixing ratio of
      oil/lecithin=1:1, the weight ratio, a lipid emulsion with a mean particle size of
      130 nm was prepared. This small particle size makes this emulsion filter
      sterilizable, which is a favorable feature for heat labile products. The
      stability of the KW-3902 lipid emulsion was assessed from the viewpoint of the
      electrostatic repulsion, and by including the oleic acid a stable lipid emulsion
      was developed, which was stable for at least 12 months at 10 and 25 degrees C and
      for 3 months at 40 degrees C. The feature of this small particle size emulsion
      was also characterized by comparing it with a conventional emulsion
      (oil/lecithin=1:0.12, the weight ratio, particle size is 220 nm). The release of
      KW-3902 from the oil particles was measured and the apparent permeability of KW
      3902 was calculated from the equation according to Fick's theory. The apparent
      permeability, P, of KW-3902 was not affected by the particle size of the emulsion
      (1.78x10(-11) cm/s for the small emulsion and 1.76x10(-11)cm/s for the
      conventional emulsion). The distribution mode of KW-3902 in the lipid emulsion
      was also discussed by considering the findings of the permeability and solubility
      of KW-3902.

PMID- 11824592
TI  - Synthetic studies of psilocin analogs having either a formyl group or bromine
      atom at the 5- or 7-position.
AB  - Psilocin analogs having either a formyl group (9-12) or a bromine atom (13-18) at
      the 5- or 7-position have been prepared for the first time. Syntheses of 5- and 7
      bromo derivatives of 4-hydroxy- (23, 24, 28) and 4-benzyloxyindole-3-carbaldehyde
      (19, 25, 29, 30), 4-benzyloxyindole-3-acetonitriles (20, 31), and 4-benzyloxy-N,N
      dimethyltryptamine (32, 34, 35) have also been established.

PMID- 11824593
TI  - Novel cross-linked polyacrylamide matrices: an investigation using gradient gel
      electrophoresis.
AB  - Gradient gel electrophoresis was used to examine the separation properties of
      novel cross-linking compounds for polyacrylamide (PAAm). At low %T and at the
      same %C protein migration difference is accentuated for bismethacrylamide cross
      linked networks relative to bisacrylamide cross-linked networks. Similar
      properties were observed for cyclic monomers at low %T. This trend is maintained
      throughout the gradient. However, at higher %T migration differential relative to
      N,N'-methylenebisacrylamide (Bis) was less pronounced. Evidence from gradient
      gels suggests that reactivity and functionality of vinyl groups impose an
      overriding control over network formation.

PMID- 11824594
TI  - Novel cross-linked homogeneous polyacrylamide gels with improved separation
      properties: investigation of the cross-linker functionality.
AB  - Polyacrylamide (PAAm) gels were synthesized using cross-linkers with their
      potential functionality (twice the number of double bonds of a cross-linker)
      varying from six to sixteen. Improved electrophoretic separation and highly
      desirable porosity and sieving properties were observed for most of the PAAm gels
      containing novel cross-linkers. An increase in the potential functionality of
      cross-linkers used in PAAm gels was an important factor, influencing the pore
      size and pore size distribution of the network.

PMID- 11824596
TI  - Use of DNase to eliminate contamination in ancient DNA analysis.
AB  - Using polymerase chain reaction (PCR) amplification, it is possible to analyze
      DNA from limited source template. This method has proved especially valuable in
      studies of ancient DNA and in forensic investigations. However, PCR reactions
      containing minimal or damaged source template are prone to contamination by DNA
      from a number of other sources. While standard protocols to prevent and/or detect
      contamination do exist, methods of eliminating contamination are needed to ensure
      the validity of results obtained. We present a method to eliminate sources of
      contamination in reagents and labware through the use of a DNase prior to PCR
      amplification without damaging even the minimal amounts of template present in
      ancient DNA samples. This method, suggested previously for forensics
      applications, appears to be effective in eliminating contamination without
      interfering with the amplification of ancient template.

PMID- 11824595
TI  - Do orientation effects contribute to the molecular weight dependence of the free
      solution mobility of DNA?
AB  - The free solution mobility of DNA increases with increasing molecular weight and
      then levels off and becomes constant at molecular weights above approximately 400
      bp (Stellwagen, N. C., Gelfi, C., Righetti, P. G., Biopolymers 1997,42, 687-703).
      To investigate whether the increase in mobility could be attributed to an
      increased orientation of the larger DNA molecules in the electric field, the free
      solution mobility of DNA was measured by capillary electrophoresis as a function
      of electric field strength. Mixtures containing 20-, 118- and 422-bp DNA
      molecules, and 20-, 422- and 2116-bp DNAs, were studied. If the larger DNA
      molecules in each mixture were oriented by the electric field, their mobilities
      should increase with electric field strength faster than the mobility of the 20
      bp oligomer, which is too small to be oriented by the electric fields used in
      this study. Instead, the ratios of the mobilities of the 118-, 422- and 2116-bp
      fragments to the mobility of the 20-bp oligomer were independent of electric
      field strength. Hence, orientation effects are not important for DNA molecules up
      to 2 kbp in size, in electric fields up to 500 V/cm in amplitude. An explanation
      is suggested.

PMID- 11824597
TI  - Improving the length-fractionation of DNA during capillary electrophoresis.
AB  - The present study develops a path-lengthening strategy for capillary
      electrophoresis of short double-stranded DNA molecules, in an aqueous solution of
      neutral polymer (hydroxypropylmethylcellulose). Tests of the dependence of
      fractionations on pulse times reveal the operation of at least one mechanism in
      addition to increase in effective path length. Electrophoresis is performed in
      the following two-stage cycles (cyclic electrophoresis): The first analysis-stage
      of each cycle is a constant field (forward) capillary electrophoresis. This
      analysis-stage reveals the length distribution of the shortest DNA molecules not
      previously analyzed. The second, enhancement-stage of each cycle is zero
      integrated field electrophoresis (ZIFE). The enhancement-stage improves the DNA
      length-fractionation for the next DNA molecules to be analyzed. A slight reverse
      migration occurs in the enhancement-stage. Increase in both peak separation and
      peak sharpness contribute to improvement in the length-fractionation of DNA
      molecules.

PMID- 11824598
TI  - Maximization of injection volumes for DNA analysis in capillary electrophoresis.
AB  - We report concentration and separation of DNA in the presence of electroosmotic
      flow (EOF) using poly(ethylene oxide) (PEO) solution. DNA fragments migrating
      against EOF stacked between the sample zone and PEO solution. To maximize the
      injection volume, several factors, such as concentrations of Tris-borate (TB)
      buffer and PEO solution, capillary size, and matrix, were carefully evaluated.
      The use of 25 mM TB buffers, pH 10.0, containing suitable amounts (less than 10
      mM) of salts, such as sodium chloride, sodium phosphate, and sodium acetate, to
      prepare DNA is essential for the concentration of large-volume samples. In the
      presence of salts, the peaks also became sharper and the fluorescence intensity
      of DNA complexes increased. Using 2.5% PEO and a 150 microm capillary filled with
      400 mM TB buffer, pH 10.0, up to 5 microL DNA samples (phiX 174 RF DNA-HaeIII
      digest or the mixture of pBR 322/HaeIII, pBR 328/Bg/I, and pBR 328/HinfI digests)
      have been analyzed, resulting in more than 400-fold improvements in the
      sensitivity compared to that by conventional injections (ca. 36 nL). Moreover,
      this method allows the analysis of 3.5 microL PCR products amplified after 17
      cycles without any sample pretreatment.

PMID- 11824599
TI  - Migration behavior of therapeutic peptide hormones: prediction of optimal
      separation by capillary electrophoresis.
AB  - A general equation that relates electrophoretic mobility of polyprotic peptide
      substances and pH of the running electrolytes is established, taking into account
      the species in solution and the activity coefficients. Modelling electrophoretic
      mobility as a function of pH can be simultaneously used for determination of
      ionization constants and selection of the optimum pH for separation of mixtures
      of the modelled compounds. The proposed relationships allow an important
      reduction of the experimental data needed for development of new separation
      methods. The accuracy of the proposed equations is verified by modelling the
      migration behavior of a heterogeneous series of polyprotic amphoteric peptide
      hormones. By calculating the values of predicted resolutions, selection of the
      optimum pH to perform separation of their mixtures becomes a rapid and simple
      process.

PMID- 11824600
TI  - Electrophoretic behavior of a highly water-soluble dendro[60]fullerene.
AB  - The aim of the present study was to develop an analytical method for measuring
      amounts of a dendro[60]fullerene (DF) which is a highly water-soluble
      [60]fullerene derivative. We tried to define a straightforward methodology using
      capillary zone electrophoresis, a method which, to our knowledge, has not yet
      been used to that purpose. Preliminary assays showed that DF has almost the same
      mobility than the electroosmotic flow (EOF) but in the opposite direction.
      Attempts were carried out to reduce the EOF and positive results were obtained by
      adding hydroxypropylcellulose to the background electrolyte. In order to define
      optimal operating conditions, a Taguchi experimental plan was used to study
      simultaneously the effects of the main parameters that are pH, ionic strength,
      methanol amount and hydroxypropylcellulose concentration. Two parameters are of
      the utmost importance as to their effect on the migration time and separation
      efficiecy: pH and ionic strength whose actions are opposite.

PMID- 11824601
TI  - Optimization of capillary electrophoretic-electrospray ionization-mass
      spectrometric analysis of catecholamines.
AB  - The capillary electrophoretic-mass spectrometric analysis (CE-MS) of
      catecholamines was optimized with coaxial sheath flow interface and electrospray
      ionization (ESI). The parameters studied included the sheath liquid composition
      and its flow rate, separation conditions in ammonium acetate buffer together with
      the ESI and cone voltages as mass spectrometric parameters. In addition, the
      effect of ESI voltage on injection as well as the siphoning effect were
      considered. The optimized conditions were a sheath liquid composition of methanol
      water (80:20 v/v) with 0.5% acetic acid, with a flow rate of 6 microL/min. The
      capillary electrophoretic separation parameters were optimized with 50 mM
      ammonium acetate buffer, pH 4.0, to +25 kV separation voltage together with a
      pressure of 0.1 psi. The most intensive signals were obtained with an ESI voltage
      of +4.0 kV and a cone voltage of +20 V. The nonactive ESI voltage during
      injection as well as avoidance of the siphoning effect increased the sensitivity
      of the MS detection considerably. The use of ammonium hydroxide as the CE
      capillary conditioning solution instead of sodium hydroxide did not affect the CE
      MS performance, but allowed the conditioning of the capillary between analyses to
      be performed in the MS without contaminating the ion source.

PMID- 11824602
TI  - Sensitivity enhancement by on-line preconcentration and in-capillary
      derivatization for the electrophoretic determination of amino acids.
AB  - This study describes an application of on-line preconcentration by large-volume
      stacking in combination with in-capillary derivatization for enhancing
      spectrophotometric detection sensitivity in capillary electrophoresis. The method
      is illustrated by an example dealing with the determination of amino acids with
      1,2-naphthoquinone-4-sulfonate as a labelling agent. Samples are dissolved in
      water in order to create a stacking process based on differences in the
      conductivity between this medium and a concentrated running buffer. The in
      capillary derivatization is accomplished following a sandwich procedure in which
      the sample is inserted between two segments of reagent. Amino acid derivatives
      are obtained and separated in a fused-silica capillary with a sodium borate
      electrolyte buffer using 2-propanol as an organic modifier. The method is applied
      to the analysis of amino acids in pharmaceutical and feed samples. A good
      concordance between the predicted values and those obtained with the standard
      method is observed, with overall quantification error below 5%. The proposed
      procedure allows the detection limits sensitivity to be enhanced in 1000-fold
      with respect to conventional precapillary derivatization.

PMID- 11824603
TI  - Comparative studies of various run buffers for chiral capillary electrophoresis
      using chiral crown ether as a chiral selector.
AB  - In the capillary electrophoretic separation of primary amine enantiomers using
      (+)-(18-crown-6)-tetracarboxylic acid (18C6H4) as a chiral selector, the presence
      of run buffer constituents such as tris(hydroxymethyl)aminomethane (Tris) or Na+
      competing with analytes for 18C6H4, diminishes the effectiveness of 18C6H4. In
      order to determine appropriate buffer systems for 18C6H4, various run buffer
      cationic components including Tris, 1,3
      bis[tris(hydroxymethyl)methylamino]propane, bis(2
      hydroxyethyl)iminotris(hydroxymethyl)methane, triethanolamine,
      tetramethylammonium, and Na+ were compared. Quantitative studies of the effects
      of the competitive constituents were carried out by measuring the electrophoretic
      mobilities of histidine as a function of the 18C6H4 concentration. We also
      derived a simple equation to estimate the optimal chiral selector concentration
      for a maximum mobility difference in the presence of a competitive inhibitor.

PMID- 11824604
TI  - Substituting Coomassie Brilliant Blue for bromophenol blue in two-dimensional
      electrophoresis buffers improves the resolution of focusing patterns.
AB  - In a new area of postgenomics challenges, the optimization of protein
      identification has become a central goal in microbiochemistry. In this work, we
      demonstrate that the substitution of Coomassie Brilliant Blue for bromophenol
      blue in two-dimensional electrophoresis (2-DE) buffers improves the focusing of
      whole proteins from Pseudomonas aeruginosa. This improvement of focusing concerns
      more particularly basic proteins. This enhancement may be attributed to a better
      transfer from the first to the second dimension, which probably highlights an
      increase in the solubility of proteins in the IPG strips. Hence, the use of an
      efficient tracking dye in the 2-DE buffers may enlarge protein recovery on
      proteome maps.

PMID- 11824605
TI  - A proteome database of human primary T helper cells.
AB  - We have established the first public database of human primary T helper cell
      proteome using two-dimensional electrophoresis (2-DE) and matrix assisted laser
      desorption/ionization-time of flight-mass spectrometry. For the database, CD4+
      human T cells were activated with anti-CD3+anti-CD28 antibodies and metabolically
      labeled with [35S]methionine for 24 h. Cells were lysed and proteins were
      separated by 2-DE. About 1500 protein spots were detected in the resulting 2-DE
      gels with silver staining, and 2000 spots with autoradiography. We have
      identified 91 proteins from the 2-DE gels using peptide mass fingerprinting, and
      annotated them to our database. The identified proteins are also linked to SWISS
      PROTand NCBI protein databases. Our database is available via the Internet at
      http://www3.btk.utu.fi:8080/Genomics/Proteomics/Database.

PMID- 11824606
TI  - Autoimmune pancreatic disease: preparation of pancreatic juice for proteome
      analysis.
AB  - The identification of pancreatic proteins is generally hampered by the high
      content and activity of proteases produced by this organ. The aim of this work
      was the development of a protocol for the analysis of pancreatic juice by two
      dimensional (2-D) gel electrophoresis allowing consistent and reproducible
      protein analysis encompassed by high-resolution protein 2-D maps and subtle
      protein spot recognition without substantial losses due to proteases. Immobilized
      pH gradient (IPG) strips were used for the first dimension, the second dimension
      was performed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS
      PAGE). However, the key step was the sample preparation technique. Improvements
      were achieved by using several protease inhibitors (phenylmethylsulfonyl
      fluoride, aprotinin, L-1-chloro-3-[4-tosyl-amido]-7-amino-2-heptanine (TLCK)-HCI,
      Complete) to prevent degradation of the proteins. The application of different pH
      ranges was a valuable step for getting an overview of the expressed protein
      pattern. These investigations resulted in well-resolved 2-D maps with a high
      reproducibility.

PMID- 11824607
TI  - A reliable and simple method for two-dimensional electrophoresis and
      identification of HeLa nuclear alkaline nucleic acid-binding proteins using
      immobilized pH gradient.
AB  - Alkaline proteins were separated by two-dimensional electrophoresis, using
      isoelectric focusing in commercial pH 6-11 immobilized pH gradients (IPG), in
      order to identify nucleic acid-binding proteins by South- or Northwestern
      blotting. The corresponding spots were chosen according to their DNA or RNA
      binding properties, excised, and submitted to a simplified tryptic digestion and
      peptide extraction protocols. Matrix assisted laser desorption/lonization-time of
      flight (MALDI-TOF)-mass spectrometry was used to identify 36 out of 39 excised
      protein spots. The database search output gave a set of proteins already known as
      DNA or RNA binding factors, some of which have enzymatic activity (RNA
      processing, splicing, cleavage, homologous DNA recognition, transcription
      factor). The method can be performed entirely using commercially available
      products, from HeLa nuclear extracts to IPG-gradients.

PMID- 11824608
TI  - A high-resolution reference map for cytoplasmic and membrane-associated proteins
      of Corynebacterium glutamicum.
AB  - We present a high-resolution reference map for soluble proteins obtained from
      Corynebacterium glutamicum cells grown in glucose minimal medium. The analysis
      window covers the pl range from 4-6 and the molecular mass range from 5-100 kDa.
      Using overlapping narrow immobilized pH gradients for isoelectric focusing, 970
      protein spots were detected after second-dimensional separation on SDS
      polyacrylamide gels and colloidal Coomassie-staining. By tryptic peptide mass
      fingerprinting 169 protein spots were identified, representing 152 different
      proteins including many enzymes involved in central metabolism (18), amino acid
      biosynthesis (24) and nucleotide biosynthesis (11). Thirty-five of the identified
      proteins have no known function. A comparison of the observed and the expected
      physicochemical properties of the identified proteins indicated that nine
      proteins were covalently modified, since variants with apparently identical
      molecular mass, but differing pl were detected. The N-termini of eight proteins
      were determined by post-source decay (PSD) analysis of selected peptides. In
      addition to the soluble proteins, a map of the membrane-bound proteins within the
      pl range 4-7 is presented, which contains 660 protein spots, 22 of which were
      identified, representing 13 different proteins.

PMID- 11824609
TI  - Effects of high-molecular-mass substrates on protein migration during sodium
      dodecyl sulfatepolyacrylamide gel electrophoresis.
AB  - Substrate-sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE)
      has become a popular procedure for the separation and identification of active
      fractions present in enzyme mixtures due to its relative simplicity. Procedures
      including high-molecular-mass substrates within the gel, such as starch for
      identification of amylase activity, and protein substrates, including gelatin,
      casein, and collagen, for revealing protease activity, have been described. SDS
      PAGE separation under denaturing conditions is dependent on the molecular mass of
      the proteins and on the effective pore size of the gels, the last factor being
      affected by the inclusion of high-molecular-mass substrates into the
      polyacrylamide matrix. In order to quantify the effect of the addition of
      increasing concentrations of such substrates on protein migration, starch,
      gelatin, and casein were included in gels in which polyacrylamide concentration
      was kept constant. High-molecular-mass substrates decreased migration of proteins
      ranging from 6.5 to 205 kDa, although the migration pattern, and thereby the
      accuracy of the assignation of relative molecular masses to proteins separated on
      those gels, was practically unaffected. The substitution of glycine, as the
      carrying ion, by Tricine in denaturing electrophoresis buffer systems resulted in
      an improvement of the migration of proteins in substrate-containing gels. Results
      suggested that zymograms including substrates remain a valuable procedure for the
      separation and the relative molecular mass assignation of active enzyme
      fractions.

PMID- 11824611
TI  - Changes in protein synthesis and identification of proteins specifically induced
      during solventogenesis in Clostridium acetobutylicum.
AB  - At the end of the exponential growth phase the Gram-positive bacterium
      Clostridium acetobutylicum performs a metabolic switch from classical sugar
      fermentation accompanied by the production of acetate and butyrate to
      reinternalization and oxidation of these acids to acetone and butanol. Protein
      synthesis in acidogenic and solventogenic C. acetobutylicum cells was compared by
      two-dimensional gel electrophoresis of radioactively labeled proteins. The
      results show that the switch from acid to solvent production is accompanied by
      dramatic changes in the protein pattern. During solventogenesis, the synthesis of
      52 proteins out of 130 analyzed was increased more than twofold, the synthesis of
      34 proteins decreased to less than half as compared with synthesis in acidogenic
      cells. The changes in protein synthesis were generally reflected by changes in
      the abundance of the respective proteins, as determined from quantitative
      analysis of silver-stained second-dimensional gels. Nine proteins induced during
      solventogenesis were identified by N-terminal microsequencing. One of these
      proteins, the acetoacetate decarboxylase, is directly involved in
      solventogenesis. Other proteins synthesized in higher amounts during
      solventogenesis were three general stress proteins (DnaK, GroEL, Hsp 18), two
      enzymes involved in serine biosynthesis (serine aminotransferase and 3
      phosphoglycerate dehydrogenase) as well as a seryl-tRNA synthetase. mRNA analysis
      provided evidence that the latter three are encoded by genes organized in an
      operon and are transcriptionally induced at the onset of solventogenesis. The
      proteins acetoacetate decarboxylase and Hsp 18 occurred in two variants,
      indicating possible covalent modification of these proteins.

PMID- 11824610
TI  - Determination of the angiotensin-converting enzyme inhibitor quinapril and its
      metabolite quinaprilat in pharmaceuticals and urine by capillary zone
      electrophoresis and solid-phase extraction.
AB  - Quinapril is an antihypertensive drug commonly used in the treatment of
      hypertension and congestive heart failure. In this work, a capillary zone
      electrophoresis system is optimized for the analysis of quinapril and its active
      metabolite quinaprilat in urine, as well as for the determination of the drug and
      its combination with hydrochlorothiazide in pharmaceuticals. The separation takes
      place in a fused-silica capillary. The running electrolyte consists of a 60 mM
      borate buffer solution, pH 9.5. The analysis of urine samples requires a previous
      extraction step using C8 solid-phase cartridges. Under the optimum experimental
      conditions, the separation of the two analytes and the internal standard takes
      less than 5 min. The detection limits obtained (75 and 95 ng/mL for quinapril and
      quinaprilat, respectively) allow the application of the electrophoretic method to
      the determination of the drug and its metabolite in urine samples obtained from
      four patients treated with quinapril.

PMID- 11824613
TI  - Maize pollen enzymes after two-dimensional polyacrylamide gel electrophoresis in
      the presence or absence of sodium dodecyl sulfate.
AB  - Twelve enzymes from mature pollen grains of maize were separated by two
      dimensional polyacrylamide gel electrophoresis (2-D PAGE). The separation in the
      second dimension was both in the presence and absence of sodium dodecyl sulfate
      (SDS). Ten of the investigated enzymes lost activity after separation in the
      presence of SDS, but those of esterases and acid phosphatase could be recovered.
      On the other hand, 2-D electrophoresis without SDS is suitable for the analysis
      of maize pollen pectinesterase, malate dehydrogenase, glutamic-oxalacetic
      transaminase, diaphorase, superoxide dismutase, and phosphoglucose isomerase. 1-D
      PAGE and isoelectric focusing (IEF) are sufficient to analyze glucose-6-phosphate
      dehydrogenase, alcohol dehydrogenase, shikimic dehydrogenase, and glutamate
      dehydrogenase. The possibility of applying 2-D electrophoresis for the analysis
      of enzymes from single stigma and stigma exudate is dicussed.

PMID- 11824612
TI  - Proteome analysis and identification of symbiosis-related proteins from Medicago
      truncatula Gaertn. by two-dimensional electrophoresis and mass spectrometry.
AB  - Time-course analysis of root protein profiles was studied by two-dimensional gel
      electrophoresis and silver staining in the model plant Medicago truncatula,
      inoculated either with the arbuscular mycorrhizal fungus Glomus mosseae or with
      the nitrogen fixing bacterium Sinorhizobium meliloti. Protein modifications in
      relation to the development of both symbioses included down- and upregulations,
      as well as newly induced polypeptides. Matrix assisted laser
      desorption/ionization-time of flight-mass spectrometry after trypsin digestion
      clearly identified one polypeptide induced in nodulated roots as a M. truncatula
      leghemoglobin. Internal sequencing with a quadrupole time-of-flight mass
      spectrometer and database searches confirmed the induction of proteins previously
      described in root symbioses, and revealed the implication of other proteins. In
      nodulated roots, one polypeptide was identified as an elongation factor Tu from
      S. meliloti, while another one could not be assigned a function. In mycorrhizal
      roots, analyzed proteins also included a protein of unknown function, as well as
      a glutathione-S-transferase, a fucosidase, a myosin-like protein, a serine
      hydroxymethyltransferase and a cytochrome-c-oxidase. These results emphasize the
      usefulness of proteome analysis in identifying molecular events occurring in
      plant root symbioses.

PMID- 11824614
TI  - A proteomic approach to rapidly elucidate oligodendrocyte-associated proteins
      expressed in the myelinating rat optic nerve.
AB  - The lack of cDNA libraries derived from myelinating oligodendrocytes has hampered
      attempts to identify proteins associated with myelination during normal
      development or with remyelination after insult or disease. We, therefore,
      established a new method to elucidate such proteins by coupling the techniques of
      X-irradiation, two-dimensional (2-D) gel electrophoresis, and mass spectrometry.
      Specifically, 2-D gel protein profiles of normal optic nerves were compared with
      those of X-irradiated rat optic nerves, which were absent of oligodendrocytes, to
      elucidate oligodendrocyte-associated proteins. The subsequent identification of
      these oligodendrocyte-associated proteins was accomplished by mass spectrometry.
      The results presented in this paper demonstrate the potential of the X-irradiated
      optic nerve model system combined with proteomic techniques to rapidly elucidate
      oligodendrocyte-associated proteins expressed in vivo.

PMID- 11824615
TI  - DNA electrophoresis in agarose gels: a simple relation describing the length
      dependence of mobility.
AB  - Electrophoretic mobilities of DNA molecules ranging in length from 100 to 10 000
      base pairs (bp) were measured in gels of eleven concentrations of agarose from
      0.5 to 1.5%. Excellent fits of the dependence of mobility on DNA length were
      obtained with the relationship [equation: see text] showing an e(-L/gamma)
      crossover, where L is the length of a DNA fragment and gamma is a crossover
      length ranging from 8000 to 12000 bp. The other parameters in the fit are mu(s)
      the mobility of short DNA with unit charge in the limit as length is extrapolated
      to zero, and muI, the mobility of long DNA as length is extrapolated to infinity.
      This exponential relationship should be a useful interpolation function for
      determining DNA lengths over a wide range. The simplicity of this relationship
      may be of more fundamental significance and suggests that some common feature
      dominates the electrophoresis of double stranded DNA fragments in agarose gels,
      regardless of length.

PMID- 11824617
TI  - The 48 bp centromeric repeat is a functionally conserved motif in great apes and
      man showing protein-binding properties.
AB  - The centromere-kinetochore complex is a chromosomal assembly site including
      repeat motifs and protein binding properties thus mediating chromosome motility
      and mitotic regulation. Next to the alpha-satellite DNA family as well as human
      satellite III DNA, contribution of other repetitive sequences has to be strongly
      considered in centromere function. Here, we report the identification of
      centromeric 48 bp motifs, isolated from chimpanzee and orang-utan using an
      orthologous human DNA probe. Applying Southern hybridization we show that these
      sequences are restricted to hominoid species. Diminishing hybrid formation in
      gibbons suggested that the 48 bp repeat originated approximately 25-20 million
      years ago. Consistently, both chimpanzee as well as human repeat probes failed to
      generate any hybridization signal with the monkey species Cercopithecus aethiops
      and Aotes trivirgatus. Sequence deviations from the consensus of human repeat
      monomers of 6% and 10.4% in chimpanzee and orang-utan, respectively, were found
      within a 16 bp region of the 48 bp repeat units. Gel mobility shift assays using
      chimpanzee repeat dimers as probes revealed peptide-binding properties with human
      and chimpanzee nuclear extracts. Species-specific DNA-protein complexes remained
      unaffected by competition studies and indicated the presence of at least one
      novel interacting protein consisting of two subunits with 90 and 95 kDa. Our data
      suggest that the 48 bp repeat, next to alpha-satellite DNA, provides essential
      sequence information for specific DNA-protein interaction and they imply
      phylogenetic conservation of these binding properties in primates. The complex is
      likely involved in the proper formation and/or function of mammalian centromeres.

PMID- 11824616
TI  - Aberrant expression of signaling-related proteins 14-3-3 gamma and RACK1 in fetal
      Down syndrome brain (trisomy 21).
AB  - Although Down Syndrome (DS, trisomy 21) is the most frequent isolated cause of
      mental retardation, information on brain protein expression and in particular
      protein expression of signaling-related proteins is limited. Impaired signaling
      in DS involving different signaling systems has been proposed and the
      availability of fetal brain along with recent proteome technologies unambiguously
      identifying individual brain proteins made us study individual signaling factors
      in the brain. We studied fetal brain cortex of controls (n = 7) and DS (n = 9)
      from early second trimester of gestation by two-dimensional gel electrophoresis
      with subsequent matrix-assisted laser/desorption ionization (MALDI)
      identification followed by quantification with specific software. Four 14-3-3
      protein isoforms, mitogen-activated protein kinase 1, receptor for activited
      kinase 1 (RACK1), constitutive photomorphogenesis (COP9) complex subunit 4 and
      cAMP-dependent protein kinase type II have been identified. Quantification showed
      that protein 14-3-3 gamma (means +/- standard deviation of controls: 10.18+/-2.30
      and of DS 4.20+/-1.19) and two spots assigned to RACK1 (controls spot 1: 4.15+/
      2.45 and DS 1.95+/-0.93; controls spot 2: 5.08+/-2.4 vs. DS: 2.56+/-1.19) were
      significantly decreased in DS cortex. Reduced 14-3-3 gamma may represent impaired
      neuronal differentiation, synaptic plasticity and impaired signaling by PKC and
      Raf while decreased RACK1 (anchoring protein receptor for activated C-kinase) may
      reflect or generate deranged beta-II- protein kinease C (PKC) function with the
      putative biological meaning of aberrant migration and neuritic outgrowth in DS
      early in life.

PMID- 11824618
TI  - Single-strand conformation polymorphism-based analysis of mitochondrial
      cytochrome c oxidase subunit 1 reveals significant substructuring in hookworm
      populations.
AB  - Sequence heterogeneity in a portion of the mitochondrial cytochrome c oxidase
      subunit 1 gene (pcox1) was measured for the hookworms, Ancylostoma caninum from
      Australia, A. duodenale from China, and Necator americanus from China and Togo
      using single-strand conformation polymorphism (SSCP) analysis combined with DNA
      sequencing. The pcox1 sequences were characterised for individual nematodes
      displaying genetic variation within each of the three species, and those were
      compared with pcox1 sequences of four other species of hookworm. While
      intraspecific variation in the pcox1 sequence ranged from 0.5 to 8.6% for A.
      caninum, 0.3 to 3.3% forA. duodenale, and 0.3 to 4.3% for N. americanus,
      interspecific differences varied from 4.8 to 12.9%. Sequence data also provided
      information on nucleotide compositions and substitution patterns. Genetically
      distinct groups were detected within A. caninum and A. duodenale, indicating
      significant population substructuring within these species. Also, N. americanus
      individuals from China all differed from those from Togo at four nucleotide
      positions, supporting a previous proposal (based on ribosomal DNA sequence data)
      that N. americanus may represent a species complex. The findings indicated the
      value of pcox1 sequence data and the mutation scanning approach for studying the
      genetic structures of hookworm populations, which should have important
      epidemiological relevance.

PMID- 11824619
TI  - Design of a fraction collector for capillary array electrophoresis.
AB  - This paper describes a prototype instrument for high-throughput fraction
      collection with capillary array electrophoresis (CAE). The design of the system
      was based on a comprehensive collection approach, in which fractions from all
      capillaries were simultaneously collected in individual collection microwells in
      predefined time intervals. The location of the fractions in the microwells on the
      collection plate was determined by monitoring the individual zone velocities
      close to the end of each capillary. The collection microwell plate was fabricated
      from buffer-saturated agarose gel, which maintained permanent electrical contact
      with the separation capillaries during the collection process. Since the
      collection gel plate consisted of over 90% water, liquid evaporation from the
      collection wells was minimized. A 12-capillary array instrument was built with
      two-point detection using a side illumination scheme. The collection performance
      was demonstrated by reinjection of selected fractions of a double-stranded DNA
      (dsDNA) separation. The identity of collected DNA fragments was confirmed by PCR
      and sequencing.

PMID- 11824620
TI  - Optimisation of probe concentration in indirect photometric detection in
      capillary electrophoresis using highly absorbing dyes.
AB  - In indirect photometric detection in capillary electrophoresis, the concentration
      of the absorbing probe ion in the background electrolyte should be as high as
      possible in order to increase the dynamic range of the detection method. For
      relatively low absorptivity probes (epsilon < 2000 L mol(-1)cm(-1)) used under
      typical conditions (75 microm ID capillary) the maximum probe concentration is
      normally limited by the separation current. However, for medium (epsilon
      approximately/= 2000-15000 L mol(-1)cm(-1)) and especially for high (epsilon >
      15000 L mol(-1)cm(-1)) absorptivity probes such as dyes, the maximum
      concentration may be limited by the background absorbance of the electrolyte
      which must fall within the linearity range of the detector. In this work, it is
      shown that another practical factor limiting the probe concentration is the
      adsorption of probe onto the capillary wall at higher concentrations, resulting
      in unstable baseline and increased noise. Use of a zwitterionic surfactant to
      suppress adsorption enabled the concentration of a model probe anion (tartrazine)
      to be increased by a factor of six times (to 3 mM). This resulted in significant
      improvements in peaks shapes, resolution between peaks, detection sensitivity and
      linear calibration range for the analyte anions. Baseline separation of a test
      mixture was maintained up to 7.5 mM total concentration of sample coions injected
      (13.7 nL) for the 3 mM electrolyte, with detection limits ranging from 0.63 to
      0.94 microM. Peak height reproducibility (over 20 consecutive injections) was
      improved (values ranging from 1.1 to 1.9%) compared with electrolytes containing
      lower concentrations of the probe. Overall, the optimised, higher concentration
      probe electrolyte provided the sensitivity benefits of highly absorbing probes
      with the additional benefits of ruggedness and improved stacking, peak shapes and
      resolution.

PMID- 11824621
TI  - Large-volume stacking in capillary electrophoresis using a methanol run buffer.
AB  - Highly sensitive nonaqueous capillary electrophoresis of weakly acidic organic
      compounds has been performed using methanol as the run buffer solvent. Methanol
      provided appropriate suppression of the electroosmotic flow and an increase in
      the electrophoretic mobilities of anionic solutes compared to water. These two
      effects allowed large-volume stacking using the electroosmotic flow pump (LVSEP)
      to be achieved for larger anions using a bare fused-silica capillary under an
      electric field of reverse polarity, whereas only fast-moving small anions were
      previously known to be suitable for LVSEP in aqueous media. A field-enhanced
      sample injection of an additional amount of analytes during the solvent plug
      removal further enhanced the limits of detection to below the nanomolar range
      with conventional UV absorption detection. Under optimum conditions, excellent
      linear responses and reproducibility in the migration times together with the
      corrected peak areas for ten analytes were obtained in the concentration range of
      10-100 nM.

PMID- 11824622
TI  - Solute-solvent interactions in micellar electrokinetic chromatography: IV.
      Characterization of electroosmotic flow and micellar markers.
AB  - A wide study of the compounds and procedures mostly used to determine the
      electroosmotic flow (EOF) and micelle elution times has been done in seven
      different micellar electrokinetic chromatography (MEKC) systems. These systems
      are formed from mixtures of an aqueous buffer with the surfactants sodium dodecyl
      sulfate, lithium dodecyl sulfate, lithium perfluorooctane sulfonate, sodium
      cholate, sodium deoxycholate, tetradecyltrimethylammonium bromide and
      hexadecyltrimethylammonium bromide. The solvation parameter model has been used
      to evaluate the usefulness of the compounds studied as EOF or micellar markers in
      each of the seven MEKC systems. It is demonstrated that methanol, acetonitrile
      and formamide are the best EOF markers, and that dodecanophenone is the best
      micellar marker.

PMID- 11824623
TI  - Application of capillary electrophoresis-mass spectrometry for the investigation
      of the binding behavior of oxaliplatin to 5'-GMP in the presence of the sulfur
      containing amino acid L-methionine.
AB  - Capillary electrophoresis-electrospray ionization-mass spectrometry (CE-ESI-MS)
      has been used for investigating the influence of the sulfur containing amino acid
      L-methionine (L-Met) on the binding behavior of oxaliplatin (trans-R,R
      diaminocyclohexane-(oxalato)platinum(II)) to 5'-GMP. L-Methionine competes with
      5'-GMP for the platinum binding site and forms as well as 5'-GMP adducts with
      oxaliplatin. The formation of the prognosed complexes [Pt(DACH)(L-Met-S,N)]+ and
      [Pt(DACH)(5'-GMP)2]2- (DACH = 1,2-diaminocyclohexane) could be proved directly by
      using CE-ESI-MS. Furthermore, we could now bring forward proofs, that the
      coordination of 5'-GMP with oxaliplatin is inhibited by L-methionine and could
      show, that the 5'-GMP ligands of the [Pt(DACH) (5'-GMP)2]2- complex can be
      replaced slowly by L-methionine whereas methionine can not be replaced by GMP.

PMID- 11824624
TI  - Differential staining of western blots of avian egg white glycoproteins using
      diverse lectins.
AB  - Avian egg white glycoproteins which differ in structure and carbohydrate
      composition, vary in their interactions with diverse lectins. Generally, wheat
      germ agglutinin (WGA) and concanavalin A (Con A) are used for the identification
      and separation of those of the chicken. In the present study, interactions of a
      battery of lectins, including: the above two, several galactophilic lectins (from
      Aplysia gonad (AGL), Erythrina corallodendron (ECorL), peanut (PNA) and
      Pseudomonas aeruginosa (PA-IL)), and fucose-binding lectins (from Ulex europaeus
      (UEA-I), Ulva lactuca (ULL) and P. aeruginosa (PA-IlL), which also binds mannose)
      with chicken, quail and pigeon egg white glycoproteins, were examined using both
      hemagglutination inhibition and Western blot analyses. The chicken egg white
      glycoproteins interacted most strongly with WGA, followed by Con A >> AGL = PA
      IlL. The quail glycoprotein order of affinities was: Con A >> WGA = AGL = PA-IlL,
      while that of the pigeon was: AGL > PA-IL > WGA > Con A = PA-IlL. The blocking of
      the other lectins by the egg whites were insignificant. The results demonstrated
      the selectivity and efficiency of the five most reactive lectins for differential
      tagging of avian egg white glycoproteins and unveiled the profound heterogeneity
      of the latter, as well as the possible potential lectin usage for improving
      purification and quality control of the desired glycoproteins.

PMID- 11824625
TI  - Measurement of thiol-containing amino acids and phytochelatin (PC2) via capillary
      electrophoresis with laser-induced fluorescence detection.
AB  - An analytical method for determining thiols and phytochelatins using high
      performance capillary electrophoresis coupled with laser-induced fluorescence
      detection is presented. The technique utilizes the labeling of thiols with the
      fluorescent reagent 5-bromomethylfluorescein (5-BMF), which is excited by a 488
      nm argon ion laser and fluoresces at 515 nm. The paper describes the
      determination of the optimal conditions for reaction of 5-BMF with thiols as well
      as the parameters for electrophoresis runs that produce optimal electropherogram
      peaks. The technique is shown to be very sensitive for cysteine, cysteinyl
      glycine, gamma-glutamyl-cysteine, glutathione and (gamma-glutamylcysteinyl)2
      glycine (PC2). Concentrations as low as 25 nmol/L and amounts as low as 1 fmol
      were detected for glutathione. Sensitivity for detection of PC2 was somewhat
      lower. The method was shown to be simple, rapid and accurate and should
      facilitate measurement of thiol-containing amino acids, peptides and
      phytochelatin (PC2) in small volumes of extracts obtained from biological tissue.

PMID- 11824626
TI  - Determination of some anti-human immunodeficiency virus nucleosides by capillary
      zone electrophoresis-tandem mass spectrometry.
AB  - We describe the analysis of two potent anti-human immunodeficiency virus reverse
      transcriptase (RT-HIV) inhibitors, zidovudine (AZT) and stavudine (d4T), among a
      pool of natural nucleosides (A, C, G, U, T) by capillary zone electrophoresis
      (CZE)-ionspray-tandem mass spectrometry (MS/MS) in positive ion mode. Several
      volatile formic acid-ammonia buffers having the same ionic strength (50 mM) but
      different pH values varying in the 9-11 pH range were prepared and tested to
      determine the best electrophoretic migration conditions. Quantitative CZE-MS/MS
      analysis was performed using selected reaction monitoring (SRM) mode. Finally,
      this CZE-MS/MS procedure opens the possibility for future determination of
      several nucleoside RT-HIV inhibitors in cell pool samples.

PMID- 11824627
TI  - Chiral separation of benzoporphyrin derivative mono- and diacids by laser induced
      fluorescence-capillary electrophoresis.
AB  - A method for the separation of benzoporphyrin derivative mono- and diacid (BPDMA,
      BPDDA) enantiomers by laser induced fluorescence-capillary electrophoresis (LIF
      CE) has been developed. By using 300 mM borate buffer, pH 9.2, 25 mM sodium
      cholate and 10% acetronitrile as electrolyte, +10 kV electrokinetic sampling
      injection of 2 s and an applied +20 kV voltage across the ends of a 37 cm
      capillary (30 cm to the detector, 50 microm ID), all six BPD stereoisomers were
      baseline-separated within 20 min. Formation constants, free electrophoretic and
      complexation mobilities with borate and cholate were determined based on dynamic
      complexation capillary electrophoresis theory. The BPD enantiomers can be
      quantitatively determined in the range of 10(-2)-10(-5) mg mL(-1). The
      correlation coefficients (r2) of the least-squares linear regression analysis of
      the BPD enantiomers are in the range of 0.9914-0.9997. Their limits of detection
      are 2.18-3.5 x 10(-3) mg mL(-1). The relative standard deviations for the
      separation were 2.90-4.64% (n = 10). In comparison with high-performance liquid
      chromatography (HPLC), CE has better resolution and efficiency. This separation
      method was successfully applied to the BPD enantiomers obtained from a matrix of
      bovine serum and from liposomally formulated material as well as from studies
      with rat, dog and human microsomes.

PMID- 11824628
TI  - Possibilities to improve automation, speed and precision of proteome analysis: a
      comparison of two-dimensional electrophoresis and alternatives.
AB  - Proteome analysis requires fast methods with high separation efficiencies in
      order to screen the various cell and tissue types for their proteome expression
      and monitor the effect of environmental conditions and time on this expression.
      The established two-dimensional gel electrophoresis (2-DE) is by far too slow for
      a consequential screening. Moreover, it is not precise enough to observe changes
      in protein concentrations. There are various approaches that promise faster,
      automated proteome analysis. This article concentrates on capillary (CT
      isoelectric focusing coupled to mass spectrometry (CIEF-MSn) and preparative IEF
      followed by size-exclusion chromatography, hyphenated with MS (PIEF-SEC-MS).
      These two approaches provide a similar separation pattern as the established 2-DE
      technique and therefore allow for the continued use of data based on this
      traditional approach. Their performances have been discussed and compared to 2
      DE, evaluating 169 recent articles. Data on analysis time, automation, the
      detection limit, quantitation, peak capacity, mass and pI accuracy, as well as on
      the required sample amount are compared in a table.

PMID- 11824629
TI  - Approaches to molecular imprinting based selectivity in capillary
      electrochromatography.
AB  - The work done during the past decade in order to adapt molecularly imprinted
      polymers (MIPs) to the capillary format and subsequently use these highly
      selective matrices for capillary electrochromatography (CEC) are reviewed in this
      article. MIPs are prepared utilizing a templated polymer synthesis where the
      template addresses the selectivity of the resulting polymer. These polymers
      possess binding characteristics that are comparable to the biological antibodies.
      Due to the polyclonality of the binding sites in the MIP, the separation result
      in severe peak broadening and tailing when performed in the isocratic mode. This
      was seen early in the development of MIPs as selective stationary phases in
      liquid chromatography (LC). As a mean of decreasing these problems, much effort
      was put into adapting the MIP to fit in CEC systems, that offers an efficiency
      that is superior to that in LC. Aiming to increase the efficiency of the MIP-CEC
      systems, different MIP formats have been developed that can be divided into three
      conceptually different categories, i.e., the monolithic, the microparticle and
      the coating. The strive for MIP formats that can be used in small bore
      capillaries has led to the development of MIP formats applicable to miniaturized
      systems approaching the chip format. Although prepared in order to perform MIP
      CEC mediated separations, these formats can be used in a broad range of
      applications were the characteristics of the MIP, e.g. stability, selectivity and
      cost efficiency, could offer an interesting solution to cover the needs.

PMID- 11824630
TI  - Recent applications of capillary electrochromatography.
AB  - A review is presented of the most important recent applications of capillary
      electrochromatography (CEC) for the analysis of acidic, basic, and neutral
      compounds, of biomolecules, environmental substances, natural products,
      pharmaceuticals, and chiral compounds. Packed-column CEC (packed-CEC), open
      tubular (OT-CEC), as well as pressure-assisted CEC (pseudo-CEC) are hereby
      considered. Papers published between July 1999 and April 2001 were taken into
      account. Applications before July 1999 have been reviewed in Electrophoresis
      1999, 20, 3027-3065.

PMID- 11824631
TI  - Recent advances in DNA sequencing by capillary and microdevice electrophoresis.
AB  - A number of significant improvements in the electrophoretic performance and
      design of DNA sequencing devices have culminated in the introduction of truly
      industrial grade production scale instruments. These instruments have been the
      workhorses behind the massive increase in genomic sequencing data available in
      public and private databases. We highlight the recent progress in aspects of
      capillary electrophoresis (CE) that has enabled these achievements. In addition,
      we summarize recent developments in the use of microfabricated devices for DNA
      sequencing that promise to bring the next leap in productivity.

PMID- 11824632
TI  - The use of light scattering for precise characterization of polymers for DNA
      sequencing by capillary electrophoresis.
AB  - The ability of a polymer matrix to separate DNA by capillary electrophoresis (CE)
      is strongly dependent upon polymer physical properties. In particular, recent
      results have shown that DNA sequencing performance is very sensitive to both the
      average molar mass and the average coil radius of the separation matrix polymers,
      which are affected by both polymer structure and polymer-solvent affinity. Large
      polymers with high average molar mass provide the best DNA sequencing separations
      for CE, but are also the most challenging to characterize with accuracy. The
      methods most commonly used for the characterization of water-soluble polymers
      with application in microchannel electrophoresis have been gel permeation
      chromatography (GPC) and intrinsic viscosity measurements, but the limitations
      and potential inaccuracies of these approaches, particularly for large or novel
      polymers and copolymers, press the need for a more universally accurate method of
      polymer molar mass profiling for advanced DNA separation matrices. Here, we show
      that multi-angle laser light scattering (MALLS) measurements, carried out either
      alone or in tandem with prior on-line sample fractionation by GPC, can provide
      accurate molar mass and coil radius information for polymer samples that are
      useful for DNA sequencing by CE. Wider employment of MALLS for characterization
      of novel polymers designed as DNA separation matrices for microchannel
      electrophoresis should enable more rapid optimization of matrix properties and
      formulation, and assist in the development of novel classes of polymer matrices.

PMID- 11824633
TI  - Recent advances in amino acid analysis by capillary electrophoresis.
AB  - Amino acids are studied extensively using capillary electrophoresis. In this
      review we will report the different researchs which have been done in the
      literature since 1998. We will describe the developments of, detection methods,
      separations of enantiomers, the new medical applications, and amino acids in food
      and plants.

PMID- 11824635
TI  - Capillary electrophoresis of proteins 1999-2001.
AB  - This review article with 223 references describes recent developments in
      capillary electrophoresis (CE) of proteins and covers papers published during
      last two years, from the previous review (V. Dolnik, Electrophoresis 1999, 20,
      3106-3115) through Spring 2001. It describes the topics related to CE of proteins
      including modeling of the electrophoretic properties of proteins, sample
      pretreatment, wall coatings, improving selectivity, detection, special
      electrophoretic techniques, and applications.

PMID- 11824634
TI  - Recent advances in capillary electrophoresis of peptides.
AB  - The article gives a comprehensive review on the recent developments in the
      applications of high-performance capillary electromigration methods, including
      zone electrophoresis, isotachophoresis, isoelectric focusing, affinity
      electrophoresis, electrokinetic chromatography and electrochromatography, to
      analysis, preparation and physicochemical characterization of peptides. The
      article presents new approaches to the theoretical description and experimental
      verification of electromigration behavior of peptides, and covers the
      methodological aspects of capillary electroseparations of peptides, such as
      strategy and rules for the rational selection of separation mode and experimental
      conditions, sample treatment, suppression of peptide adsorption to the inner
      capillary wall, new developments in individual separation modes and new designs
      of detection systems. Several types of applications of capillary electromigration
      methods to peptide analysis are presented: conventional qualitative and
      quantitative analysis for determination of purity, determination in biomatrices,
      monitoring of physical and chemical changes and enzymatic conversions, amino acid
      and sequence analysis and peptide mapping of proteins. Some examples of
      micropreparative peptide separations are given and capabilities of capillary
      electromigration techniques to provide important physicochemical characteristics
      of peptides are demonstrated.

PMID- 11824636
TI  - Review applications of capillary electrophoresis to the analysis of biotechnology
      derived therapeutic proteins.
AB  - The number of proteins produced by recombinant DNA technology continues to grow
      at a rapid pace. In this review, the emphasis is on proteins that are of
      therapeutic interest. Aspects of protein analysis, such as glycoform separation
      of proteins produced in mammalian cells and the separation of oligosaccharides
      for structure elucidation, are covered. The use of antibodies as therapeutic
      proteins is growing and currently antibodies are the largest class of proteins
      produced by biotechnology. This has merited a separate section on analysis of
      antibodies by capillary electrophoresis (CE). Applications of mass spectrometry
      as an ancillary technique, used in conjunction with CE, are also covered briefly.
      This review covers the literature since 1999.

PMID- 11824637
TI  - Recent advances in capillary electrophoresis methods for food analysis.
AB  - This review article addresses recent advances in the analysis of foods and food
      components by capillary electrophoresis (CE). CE has found application to a
      number of important areas of food analysis, including quantitative chemical
      analysis of food additives, biochemical analysis of protein composition, and
      others. The speed, resolution and simplicity of CE, combined with low operating
      costs, make the technique an attractive option for the development of improved
      methods of food analysis for the new millennium.

PMID- 11824638
TI  - High-performance capillary electrophoresis of meat, dairy, and cereal proteins.
AB  - Food proteins play important roles in food functionality, nutrition, and human
      health. For these reasons, new analytical methods are continually being developed
      to separate and characterize these important proteins. High-performance capillary
      electrophoresis (HPCE) is one of the latest analytical methods to be applied to
      the separation of food proteins. This review covers methods and applications for
      the separation of three major groups of food proteins, meat, dairy, and cereal
      proteins.

PMID- 11824639
TI  - Advances ofcapillary electrophoresis in clinical and forensic analysis (1999
      2000).
AB  - In this paper, capillary electrophoresis in clinical and forensic analysis is
      reviewed on the basis of the literature of 1999, 2000 and the first papers in
      2001. An overview of progress relevant examples for each major field of
      application, namely (i) analysis of drug seizures, explosives residues, gunshot
      residues and inks, (ii) monitoring of drugs, endogenous small molecules and ions
      in biofluids and tissues, (iii) general screening for serum proteins and analysis
      of specific proteins (carbohydrate deficient transferrin, alpha1-antitrypsin,
      lipoproteins and hemoglobins) in biological fluids, and (iv) analysis of nucleic
      acids and oligonucleotides in biological samples, including oligonucleotide
      therapeutics, are presented.

PMID- 11824640
TI  - Recent advances in pharmacokinetic applications of capillary electrophoresis.
AB  - This article reviews recent capillary electrophoresis (CE)-based assays which
      were published for pharmacokinetic studies. Both the advantages and disadvantages
      of these CE-based assays are discussed based on their feasibility and the
      significance towards the better understanding of pharmacokinetics. In addition,
      as a future outlook, novel assays such as immunoaffinity CE and chip-based CE for
      analyzing drugs in biological fluids are summarized in view of their potential
      for pharmacokinetic applications.

PMID- 11824641
TI  - Analysis of antibiotics by capillary electrophoresis.
AB  - This article reviews recent developments in the characterization of antibiotics.
      Many capillary electrophoretic techniques have been utilized in their analyses,
      addressing various aspects of quantifying, profiling and monitoring. Sensitive
      electrochemical and laser-induced fluorescence detection systems have been
      utilized, demonstrating trace level determinations in clinical settings and in
      environmental samples. Different sample introduction methods have been explored,
      enhancing detection sensitivity, or reducing or eliminating sample manipulation
      prior to injection.

PMID- 11824642
TI  - Recent advances in capillary electrophoresis and capillary electrochromatography
      of pollutants.
AB  - An overview of major developments in capillary electrophoresis and capillary
      electrochromatography systems in the environmental field is presented, covering
      relevant publications between the second half of 1999 and early 2001.
      Contributions are reviewed in relation to developments in detection, sample
      preparation/preconcentration, precision and applications. Many interesting
      examples are shown and the influence of important parameters on the performance
      of developed methods is discussed.

PMID- 11824643
TI  - Capillary electrophoresis and electrochromatography of pesticides and
      metabolites.
AB  - Synthetic pesticides are important chemicals since they are widely used to
      control many types of weeds, insects, and other pests in a wide variety of
      agricultural and nonagricultural settings. This review article is aimed at
      describing the recent progress made in capillary electrophoresis (CE) and
      capillary electrochromatography (CEC) of pesticides and metabolites. The various
      electrophoretic systems and detection schemes that were introduced during the
      period extending from the second half of 1999 to the first half of 2001 for the
      CE and CEC of pesticides are discussed. Also included in this review article are
      the various approaches for trace enrichment that are involved in the analysis of
      dilute pesticide samples.

PMID- 11824644
TI  - Referral rates for a functional vision screening among a large cosmopolitan
      sample of Australian children.
AB  - The aim of this study was to investigate the incidence of functional vision
      problems in a large unselected cosmopolitan population of primary school-age
      children and to investigate whether constant clinical criteria for functional
      vision problems would be implemented by the practitioners involved in the
      screening. Refractive errors, near point of convergence, stereopsis, strabismus,
      heterophoria and accommodative facility were assessed for 2697 children (3-12
      years) of varying racial backgrounds living in Australia. The spherical component
      of the refractive error ranged from -7.75 to +9.50 D (mean +0.54 D, +/-0.79) with
      a distribution skewed towards hypermetropia; astigmatism ranged from 0 to 4.25 D
      (mean -0.16 D, +/-0.35). There was a trend towards less hypermetropia and
      slightly more astigmatism with age. Mean near point of convergence was 5.4+/-2.9
      cm, heterophoria at far and near was 0.12+/-1.58delta exophoria and 1.05+/
      2.53delta exophoria, respectively, 0.55% of children exhibited vertical phoria at
      near >0.5delta, accommodative facility ranged from 0 to 24 cycles per minute
      (cpm) (mean 11.2 cpm, +/-3.7), stereopsis varied from 20 to 800 s (") of arc with
      50% of children having 40" or better. The prevalence of strabismus was
      particularly low (0.3%). Twenty percent of the children were referred for further
      assessment based on criteria of one or more of: stereopsis >70", accommodative
      facility <8 cpm, near point of convergence (NPC) >9 cm, near exophoria >10delta
      or near esophoria >5delta, shift in eso or exophoria > or = 4delta between
      distance and near, astigmatism > or = 1 D, myopia more than -0.75 D, or hyperopia
      >+1.50 D. Post-hoc analysis of the record cards seeking the reason for further
      assessment indicates that referrals appear to have been based upon clinical
      intuition rather than on a set number of borderline or unsatisfactory results.

PMID- 11824645
TI  - A multiple regression approach to study optical components of myopia in Singapore
      school children.
AB  - PURPOSE: Previous studies on the optical components of childhood myopia adjusted
      only for age and gender or reported only the change of individual components with
      time. We perform a study to assess the association of the optical components of
      the eye contributing to the degree of myopia by building a statistical model
      which can better assess the individual effects of each optical component.
      METHODS: Children 6-12 years old with myopia of -1 to -6 D were used in this
      study. Autokeratometry was performed to determine the mean corneal power in two
      perpendicular meridia. Ultrasonography was used to determine the vitreous chamber
      depth (VCD). Ultrasonography and Scheimflug biometry were used to determine lens
      thickness (LT) and anterior chamber depth. A stepwise multiple linear regression
      was used to determine statistically significant independent variables that
      explain the variation in the mean spherical equivalent of the left eye. The
      independent variables investigated were anterior chamber length, LT, VCD, mean
      corneal power, age and gender. The first regression model used measurements of
      anterior chamber depth and LT from ultrasonography, while the second model used
      measurements from Scheimflug photography. Statistical significance was set at p <
      0.05. RESULTS: Both statistical models have the same significant independent
      variables - VCD, LT and gender, with similar estimates. In both models, VCD was
      found to have the strongest partial association with mean spherical equivalent,
      followed by gender and LT. A more myopic refractive error was associated with (1)
      a longer eye, (2) an increased LT, and (3) female gender. CONCLUSIONS: Myopia was
      associated with a longer vitreous chamber. This remained the primary determinant
      of myopia in Chinese children after consideration of other optical components.
      The effect of gender and LT on myopia requires further study. These results are
      in agreement with multiple regression analyses in Singapore adults.

PMID- 11824646
TI  - A retrospective pilot study to assess the impact of strabismus surgery on the
      corneal endothelium in children.
AB  - PURPOSE: To investigate if strabismus surgery has an impact on the corneal
      endothelium in children. METHODS: Fourteen children who had undergone
      uncomplicated strabismus surgery an average of 41 months previously (range 24-73
      months) were compared with a group of age-matched (range 5-12 years) and
      refractive error (RE)-matched (range -4.74 to +4.25 D) children. Following
      noncontact specular microscopy, areas of at least 100 cells were measured, the
      number of sides for each cell recorded, and endothelial cell density (ECD)
      calculated from the area measures. Corneal diameter was measured with a clinical
      rule, corneal curvature with a manual keratometer, central corneal thickness
      (CCT) by ultrasound pachometry, and IOP by non-contact tonometry. RESULTS: The
      average ECD (+/-S.D.) in the post-surgery group was 4467+/-627 cells mm(-2),
      which was significantly higher (p < 0.02) than in the control group (3781+/-452
      cells mm(-2)). This was because the average endothelial cell area in the surgery
      group was significantly smaller than in the control group (p < 0.005; 252+/-25
      microm2 vs 296+/-29 microm2). Differences in cell areas were slightly greater for
      smaller cells (-15.7% for five-sided cells, -15.6% for six-sided cells, -14.3%
      for seven-sided cells and -13.8% for eight-sided cells). The cell differences
      appear to be related to both a slightly smaller corneal diameter (11.00+/-0.52 mm
      vs. 11.21+/-0.58 mm) and a slightly higher CCT (0.528+/-0.033 mm vs. 0.515+/
      0.032 mm) in the post-operative group. CONCLUSION: The endothelial mosaic in
      children after strabismus surgery can show a higher than expected ECD value and
      slight cell pleomorphism. These signs indicate that there might be differences in
      eye growth and endothelial inflammatory stress associated with uneventful
      strabismus surgery.

PMID- 11824647
TI  - Application of linear regression to videokeratoscope data for tilted surfaces.
AB  - PURPOSE: To investigate the use of linear regression analysis performed on the
      tabular data display of the EyeSys videokeratoscope (VK). When a radius squared
      vs distance squared scatterplot is produced from aspheric surface data the
      equivalent conic section can be deduced from the intercept and slope of the
      linear regression line. Non-linear plots are often produced. Linear regression
      may then be applied in a number of ways. METHOD: Topographical data derived from
      both the EyeSys VK and a computer model of the instrument were analysed by three
      methods of linear regression. The resultant apical radii, p-values and predicted
      surface tilts were compared with known values. RESULTS: The three methods predict
      different surface characteristics whose errors were found to vary depending upon
      the asphericity of the surface and its tilt. CONCLUSIONS: Apical radius is most
      accurately predicted by linear regression method (1). Both p-value and tilt are
      best predicted by averaging the radius and position data for corresponding points
      in each semi-meridian before squaring the resultant points and performing linear
      regression (method 3).

PMID- 11824648
TI  - Sources of variability in the clinical photostress test.
AB  - The photostress test is a simple clinical technique that can differentiate
      between retinal and postretinal disease. Unfortunately a wide range of normal
      results have been reported in the literature and it is perhaps for this reason
      that the test has been little used by clinicians. The purpose of this
      investigation was to evaluate the effect of photostress technique, age,
      ametropia, pupil size and acuity on photostress recovery time (PSRT) in normal
      subjects. Photostress recovery time was measured in 50 healthy subjects whose
      ages ranged from 21 to 69 using three clinically applicable techniques and a
      reference technique designed to bleach a consistent amount of photopigment. The
      agreement between each clinical technique and the reference technique was
      determined. Mean photostress recovery time differed for each of the techniques
      studied. Analysis of the data obtained with the reference and the best clinical
      technique showed that age was the only factor that had a significant effect on
      PSRT. The best clinical technique involves exposing the eye to the light from the
      direct ophthalmoscope for 30 s and measuring the time taken for acuity to return
      to within one line of pre-bleach acuity. Photostress recovery time increases with
      age but is independent of pupil size, ametropia and visual acuity.

PMID- 11824649
TI  - Effects of nifedipine retard on heart rate and autonomic balance in patients with
      ischemic heart disease.
AB  - The aim of this study was to explore the effects of nifedipine retard on heart
      rate and autonomic balance in patients with ischemic heart disease. Fourteen
      patients with ischemic heart disease (12 men and two women; mean age 64 years)
      were administered nifedipine retard at a daily dose of 20-40 mg. Changes in heart
      rate and autonomic balance were studied using Holter monitoring before and after
      12 weeks of nifedipine therapy Heart rate was unchanged during sleep but was
      higher during the day after nifedipine retard administration. The high frequency
      power spectrum of heart rate variability (indicating parasympathetic activity)
      was lower during the day after nifedipine retard therapy but was unchanged during
      sleep. The low frequency power to high frequency power ratio, indicating
      sympathetic activity was unchanged during the day and during sleep. Nifedipine
      retard increased the heart rate of patients with ischemic heart disease only
      during the day and reduced parasympathetic activity.

PMID- 11824650
TI  - Angiotensin-converting enzyme activity and angiomodulatory effects of sera in
      patients with diabetic retinopathy.
AB  - Aberrant neovascularization plays a crucial role in ocular complications in
      diabetic patients. Sera from these patients contain high levels of
      angiostimulatory factors, the most important of which is vascular endothelial
      growth factor (VEGF). Many authors have described elevation of angiotensin
      converting enzyme (ACE) activity in the sera of diabetic patients. It is
      important to determine the possible relationship between these two phenomena. We
      studied ACE serum activity and VEGF concentrations in patients with type 1 and
      type 2 diabetes and retinopathy We also investigated the effect of their sera on
      cutaneous angiogenesis induced in mice by grafting healthy human mononuclear
      blood leukocytes. We found a negative correlation between the angiostimulatory
      effect and ACE level in the sera of patients with type 1 diabetes and no
      correlation between these two parameters in patients with type 2 diabetes. VEGF
      concentrations were lower and ACE activity was significantly higher in the sera
      of patients with type 1 diabetes than in the sera of those with type 2 diabetes.

PMID- 11824651
TI  - Reactive oxygen metabolites and prooxidant status in children with Down's
      syndrome.
AB  - Children with Down's syndrome suffer many diseases among which cardiovascular
      diseases, increased susceptibility to infections, leukemia, endocrine
      alterations, immune defects, nutritional disturbance and mental retardation have
      clinical relevance. It has been suggested that the pathogenesis of Down's
      syndrome involves reactive oxygen species arising from a mutation in gene
      encoding, which disproportionately elevates superoxide dismutase activity.
      Reactive oxygen species and total antioxidant capacity were evaluated using two
      new spectrophotometric methods in a selected group of 40 children with Down's
      syndrome and in 20 apparently healthy children used as controls. Reactive oxygen
      species were significantly higher (p <0.05) in children with Down's syndrome than
      in controls: 452 (+/- 72) U.Carr vs. 270 (+/- 66) U.Carr respectively. Total
      antioxidant capacity was significantly higher (p <0.05) in controls than in
      children with Down's syndrome: 380 (+/- 52) micromol hypochlorous acid (HCLO)/ml
      vs. 281 (+/- 33) micromol HCLO/ml, respectively. In fact, thiol groups
      (sulfhydryl) were significantly higher (p <0.05) in controls than in children
      with Down's syndrome: 644 (+/- 78) micromol/l vs. 462 (+/- 54) micromol/l,
      respectively Our data show how to simply measure chemical indices of oxidative
      status in serum samples from children with Down's syndrome. We determined the
      plasmatic activities of reactive oxygen metabolites and oxidative defense
      molecules. Accumulated macromolecular damage may be one of the causes of some of
      the abnormalities that are considered part of the syndrome. Therefore, children
      with Down's syndrome have to cope with a significant prooxidant environment.
      Oxidative stress causes alterations such as atherosclerosis, early aging,
      immunological default and neurologic disorders in Down's syndrome patients. The
      new test available for measuring reactive oxygen species in serum proved to be
      reliable and useful as an early marker of tissue damage.

PMID- 11824652
TI  - Influence of age on the pharmacokinetics of vapiprost, a thromboxane A2 receptor
      antagonist, and platelet aggregation: comparison of pharmacokinetics by routine
      approach and population pharmacokinetics.
AB  - The effects of a single-dose oral administration of a thromboxane A2 receptor
      antagonist, vapiprost (SN-309), on pharmacokinetic profile and inhibition of
      platelet aggregation were investigated in six healthy elderly volunteers (age: 65
      72 years) and the influence of age on these parameters was studied by comparison
      with the results obtained in phase-I data involving healthy young participants.
      Although direct comparison of pharmacokinetic parameters was inappropriate
      because of different models, high Cmax and AUC values were obtained on comparison
      with the young. The inhibition of platelet aggregation in platelet rich plasma
      induced by U-46619 or collagen was rapidly established and remained suppressed
      for more than 8 h, although the effect was short-acting compared with the
      inhibition period in the young. This suggests that dose adjustment in the elderly
      is unnecessary In addition to a routine pharmacokinetic approach to determine the
      time-profile of vapiprost, population pharmacokinetics were studied using data
      from 51 volunteers in five clinical trials including the two above-mentioned
      studies. By fitting 812 plasma-monitoring points into the two-compartment model,
      the effects of several factors including age on parameters were investigated,
      based on the nonlinear mixed effect model. Clearance in the elderly attenuated
      82.2% of that in the young, the distribution volume varied with platelet counts
      and delayed absorption was observed in volunteers with, rather than without, food
      intake. Closer bridging studies with other countries have resulted in the current
      local situation of abbreviating phase-III studies. Consequently to clarify the
      pharmacokinetic profile of the elderly in Japan and other countries, the
      population pharmacokinetics approach based on the data in the various phase I-II
      trials is useful.

PMID- 11824653
TI  - Population pharmacokinetic analysis of ephedrine in Kampo prescriptions: a study
      in healthy volunteers and clinical use of the pharmacokinetic results.
AB  - We conducted a population pharmacokinetic analysis of ephedrine, the main
      effective constituent of the two Kampo prescriptions, Sho-seiryu-to (Xiao-Qing
      Long-Tang, Formula divinitatis caeruleae minor) and Kakkon-to (Ge-Gen-Tang,
      Formula puerariae), which are routinely used in the treatment of allergic
      rhinitis. Major pharmacokinetic differences were found in AUC(0-infinity), Cmax
      and the averages of the distribution volume between the two prescriptions. Using
      the pharmacokinetic results, we also conducted a simulation-based study comparing
      the pharmacokinetic profiles of ephedrine for the usual dosage regimen, a
      constant dose D three times a day before meals, and two alternative dosage
      regimens which are often used when patients' symptoms are not improved in the
      morning using the usual dosage regimen. The results suggested that one of the two
      alternative dosage regimens, two times D before breakfast and D in the afternoon,
      was the most effective from the pharmacokinetic viewpoint. This result was in
      accordance with our clinical experience.

PMID- 11824654
TI  - Contrast sensitivity function in children: normalized notation for the assessment
      and diagnosis of diseases.
AB  - The purpose of this article is to describe a normalized notation for the
      assessment of the contrast sensitivity in children. This notation is obtained
      dividing the log contrast sensitivity value found in a patient by the
      corresponding normative contrast sensitivity data. The ratio obtained describes
      the contrast sensitivity of a patient facilitating its understanding, assessment
      and consequently effective communications. This article shows the normalized
      notation developed for children aged from 3 to 7 years old. An evaluation of the
      contrast sensitivity in healthy and amblyopic patients has been shown in order to
      explain the procedure to follow. The use of normalized notation in clinical
      procedures will provide to the clinician a better understanding of the results
      and the changes over time as well by comparison in the assessment of an ocular
      disease.

PMID- 11824655
TI  - Visual evoked potentials in patients with psoriasis vulgaris.
AB  - PURPOSE: The aim of this study is an estimation of the visual evoked potentials
      (VEP) in patients with psoriasis vulgaris. The role of the nervous system was
      pointed out in the pathogenesis of psoriasis. Also epidemiologic research
      confirms that patients with psoriasis are at increased risk of MS development.
      MATERIALS AND METHODS: A group of 30 psoriatic males aged between 18 and 54 was
      examined. The results were compared with those obtained from a group of 30
      healthy age-matched males and they were correlated with the psoriasis area and
      severity index (PASI), the skin surface area involved, duration of the disease
      and duration of the last relapse. In neurological and ophthalmological
      examinations no pathological symptoms were detected in either group. The VEP
      examination was executed using pattern reversal (pr) and pattern flash (pf)
      stimulation. RESULTS: Using pf stimulation, in the group of patients with
      psoriasis vulgaris, a statistically significant elongation in the latency of P
      100 and reduction of response amplitude, not related to the PASI, nor the skin
      surface area involved, nor duration of the last relapse, were observed.
      CONCLUSIONS: The results of the study indicate subclinical damage of the visual
      pathway in patients with psoriasis vulgaris.

PMID- 11824656
TI  - Latent ocular deviations in patients with advanced AIDS.
AB  - The purpose of this study is to determine horizontal latent ocular deviations in
      patients with advanced AIDS (CD4+ count <0.050 x 10(9)/l) and to compare with
      normal values by means of the von Graefe technique. Twenty patients aged between
      17 and 44 years with AIDS and aged-matched control groups were submitted to
      study. The AC/A ratio was also measured in both groups using the Gradient test.
      The AIDS patients showed a horizontal latent deviation value of 0.28+/-1.07delta
      exo at near (40 cm.) and 2.12+/-1.37delta eso at distance (6 m). The AC/A ratio
      obtained was 2.03+/-0.65. Statistically significant differences were obtained in
      relation to aged-matched control group at near and at distance (p<0.01). The
      horizontal latent ocular deviation at near and at distance in advanced AIDS
      patients showed lower values than the expected. The AC/A relationship also was
      lower. The results obtained in this study indicate that AIDS patients suffer a
      divergence insufficiency, which could add to other visual complaints such as
      blurred vision, photophobia, nyctalopia and reading difficulty.

PMID- 11824658
TI  - Detection of ophthalmoscopically occult maculopathy by focal electroretinography.
AB  - We performed focal electroretinography (FERG) in 10 patients with reduced vision
      of unknown cause. No patient gave a family history of uncorrectably reduced
      vision, and none had taken any drug known to damage the retina. Visual acuity
      claims ranged from 20/40 to finger counting. Color discrimination was reduced in
      all but one patient. Visual field sensitivity was reduced nonspecifically in five
      of the six patients who could perform perimetry reliably. Ophthalmoscopy showed
      no pertinent abnormality in four of 10 patients, mildly reduced foveal reflex in
      two of 10, arteriolar narrowing in two of 10, foveal pigment disturbance in one
      of 10, and preretinal gliosis in one of 10. Flash visual evoked potential (VEP)
      testing showed no abnormality in seven of 7 patients. The pattern VEP was reduced
      or delayed in five of 5 patients, only one of whom showed the expected amplitude
      loss with decreasing check size. Five patients completed full-field
      electroretinography, six patients completed fluorescein angiography, and none
      showed pertinent abnormality on either test. FERG was performed in both eyes of
      seven patients and in one eye of three others. Signals were non-recordable from
      four eyes, abnormal in nine, equivocal in three, and normal in one. The severity
      of FERG abnormality did not correlate with the severity of acuity loss. FERG
      abnormalities were found in fourteen of 17 eyes of 10 patients with vision loss
      out of proportion to clinical findings. In these patients only one of 5 pattern
      VEP tests, none of 5 full-field ERGs, and none of 7 fluorescein angiograms
      suggested correspondingly severe maculopathy. The FERG results in these cases
      mitigated suspicions of nonorganic vision loss and permitted speedier referral to
      retinal disease and low vision specialists.

PMID- 11824657
TI  - A 5-year follow-up study for distance visual acuity after low dose radiation on
      subfoveal choroidal neovascularization in age-related macular degeneration.
AB  - In a prospective study with a 5-year follow-up, we assessed the effect of a
      single series of low-dose radiation on the distance visual acuity in eyes with
      angiographically confirmed subfoveal choroidal neovascularization (CNV) in age
      related macular degeneration (ARMD). The posterior pole of 12 eyes was treated
      with 5 Gy (4 x 1.25 Gy), and 34 eyes treated with 8 Gy (4 x 2 Gy). The best
      corrected distance visual acuity was measured at the time of treatment, and
      annually thereafter for 5 years. The study obtained complete follow-up for 11
      patients in the 5-Gy group (nine classic, two occult CNVs), and 29 patients in
      the 8-Gy group (12 classic, 17 occult CNVs). At baseline, the mean distance
      visual acuity of the treated eyes was 0.16 (20/125) in the 5-Gy group, and 0.2
      (20/100) in the 8-Gy group. Five years later, an average loss of 3.2 lines was
      present in the 5-Gy group, and 4 lines in the 8-Gy group. After 5 years, an
      average loss of 2 lines was found in a control group consisting of 18 second eyes
      with low stage dry ARMD, with a mean distance visual acuity of 0.5 (20/40) at
      baseline. Statistical analyses with Wilcoxon and Mann-Whitney U-tests showed that
      a single series of low dose radiation with either 5 Gy or 8 Gy was not able to
      stabilize the distance visual acuity of eyes with subfoveal CNV in ARMD during a
      5-year follow-up.

PMID- 11824659
TI  - Saccadic eye movements are impaired in Duchenne muscular dystrophy.
AB  - Extraocular muscles are generally considered to be spared in Duchenne Muscular
      Dystrophy (DMD). However, this assumption is based mainly on clinical
      observations, as systematic eye movement recordings have been performed in a very
      limited number of cases. Our goal was to analyze several saccade parameters in a
      higher number of cases, in order to reveal a possible ocular-motor impairment in
      DMD. Data were collected from a population of 9 subjects with DMD and 9 healthy
      male subjects of comparable age as controls. We used the electrooculographic
      (EOG) technique coupled with advanced digital signal processing; saccade
      duration, amplitude, mean velocity, peak velocity and K factor (ratio mean/peak
      velocity) were measured. The DMD group showed saccades with significantly longer
      duration and lower velocity, with respect to controls; these differences were
      accounted for mainly by the largest movements, whereas there were no significant
      differences at the smallest eccentricity tested (3 deg). Neither amplitude nor K
      factor were significantly different from controls for any of the eccentricities
      tested. To our knowledge. this is the first study to suggest significant
      impairment of eye movements in Duchenne muscular dystrophy.

PMID- 11824660
TI  - Motion adaptation in chromatic motion-onset visual evoked potentials.
AB  - The aim of this study was to investigate the influence of motion adaptation on
      visual evoked potentials (VEPs) elicited by the onset of isoluminant chromatic
      motion. VEPs were recorded from the occipital cortex of human subjects using a
      sinusoidal grating stimulus of one cycle per degree which moved at either a
      velocity of 2 or 10 degrees/s and subtended a field of 7 degrees with a mean
      luminance of 30 cdm(-2). In the first experiment the effects of adaptation were
      investigated via the manipulation of the stimulus duty cycle which was varied
      between 11-90%. The results showed a significant (p < 0.001) reduction in the N2
      P2 amplitude of the chromatic response. In contrast, P1-N2 amplitude was not
      significantly affected by motion adaptation. Subsequent experiments demonstrated
      that the chromatic motion onset VEP was attenuated not only following adaptation
      to isoluminant chromatic motion, but also to luminance motion as well. These
      results indicate that the chromatic motion onset VEP is just as susceptible as
      its luminance counterpart to motion after effects (MAEs) and as a result it is
      highly likely that it is a motion specific response. Furthermore, the fact that
      the VEP shows that there are cross-adaptation effects between motion defined by
      change in colour and by change in luminance, suggests that the two types of
      motion stimuli have inputs into a common motion mechanism.

PMID- 11824661
TI  - Subnormal visual acuity syndromes (SVAS): albinism in Swedish 12-13-year-old
      children.
AB  - BACKGROUND: The vision of 12-13-year-olds in Sweden was examined in a field
      study. The study was designed as being a part of a large European-Latin American
      study, the DESAMI project. The objective was to evaluate the prevalence of
      residual amblyopia and ocular disorders, aetiologies of subnormal vision and some
      normal visual parameters in this group of children. The children had to be born
      in Sweden in 1985 in order to have the opportunity to be included in the
      voluntary screening visual examinations. The full results of the study will be
      presented elsewhere. This paper presents clinical and VEP data of those children
      who had visual acuity of 0.8 or below in one or both eyes which could not be
      increased with glasses, or other visual/eye disturbances not explained as common
      amblyopia, i.e., subnormal visual acuity or pathological visual states of unknown
      cause, SVAS (subnormal visual acuity syndromes). SUBJECTS AND METHODS: In all,
      1046 children were examined: 76 had visual disturbances of such severity that
      they were referred to a paediatric ophthalmologist (AS). Eighteen children could
      not be pathologically classified, and they were referred to another
      ophthalmological examination and VEP (visual evoked potential) recordings. VEP
      reveals an asymmetric response after monocular stimulation in albinism. RESULTS:
      Twelve children turned up for a second examination and VEP was recorded from 10
      children. Nine children showed iris translucency. Seven children showed an
      asymmetric VEP and were classified as albinos. The albinoic VEPs could be
      subdivided into two types, (1) including all parts of the response and (2) partly
      excluding the P1/P100 potential complex. The VEP response was normal, showing
      symmetry and no other abnormality, in three of the children. CONCLUSIONS: The
      results indicate that albinism is common in Sweden. A prevalence value of
      approximately 1% is about 100 times higher than previous figures. This high
      prevalence may indicate another form of heredity, with genetical contribution to
      albinism from a varying number of albino genes and varying expression in the
      phenotypes, in the Scandinavian population. It is emphasised that in
      investigations of children with SVAS, electrophysiological examinations are
      important, not only to reveal albinism but also to exclude or verify
      neurometabolic conditions, for example.

PMID- 11824662
TI  - Mechanical assist devices.

PMID- 11824663
TI  - New devices for chronic ventricular support.
AB  - Congestive heart failure affects 5 million people in the United States with
      500,000 new cases diagnosed each year. Medical and surgical therapy have helped
      many patients but when these options fail, heart transplantation remains the only
      other treatment available to help improve their condition. Heart transplantation
      suffers from the lack of a sufficient number of suitable donor organs, the
      complications of chronic immunosuppression, and many patients die while on the
      waiting list. A number of pulsatile and nonpulsatile cardiac assist devices are
      being developed to provide chronic support for patients with heart failure and to
      be an alternative to heart transplantation. It is estimated that as many as
      60,000 patients with heart failure could be helped by mechanical devices used for
      chronic support. For these devices to be effective they must provide sufficient
      cardiac output to allow patients to perform their daily activities, have a low
      risk of thromboemboli, be fully implantable thereby reducing the risk of
      infection, and have a low incidence of device malfunction requiring part or all
      of the device to be replaced. In this article, we will review several new devices
      which have been developed over the past 5 years or so and will be in human
      clinical trials in the United States soon, either as a bridge or as an
      alternative to heart transplantation.

PMID- 11824664
TI  - Temporary mechanical support.

PMID- 11824665
TI  - Developing a comprehensive mechanical support program.
AB  - As cardiac surgery centers appreciate that ventricular assist devices (VAD) can
      dramatically impact patient survival as a bridge to transplant or recovery, and
      possibly permanent therapy, increasing numbers will desire to establish
      mechanical support programs. A number of vital elements must be put in place in
      order to operate a successful mechanical support program. Of utmost importance is
      the assembly of a dedicated team focused on comprehensive care of critically ill
      patients in need of circulatory support. An ongoing commitment from
      anesthesiologists, cardiologists, nephrologists, and other support staff is
      essential. Selection of complementary assist devices should be made to cover the
      spectrum of required support scenarios, both short- and long-term. Outpatient
      therapy has become increasingly important in mechanical cardiac assistance and
      establishment of an office where "LVAD coordinators" see outpatients facilitates
      this aspect of the program. Critically ill patients in need of cardiac assistance
      may benefit from specialized medical therapies such as: (1) intravenous arginine
      vasopressin for vasodilatory hypotension; (2) inhaled nitric oxide for right
      heart failure; (3) aprotinin to reduce hemorrhage; and (4) early enteral feeding
      in an effort to reduce infectious complications and improve rehabilitation
      following VAD implantation. A regional network with spoke hospitals centered
      around a hub hospital with long-term VAD and heart transplant programs can
      improve survival of patients with postcardiotomy cardiogenic shock via early
      transfer to the hub hospital. In this article, we describe the components of our
      mechanical support program that have allowed us to successfully support patients
      with heart failure in need of circulatory support.

PMID- 11824666
TI  - Nursing and psychosocial issues of patients on mechanical support.
AB  - Mechanical support technology continues to evolve. Ongoing research has led to
      more efficient devices allowing for discharge to outpatient or home settings.
      From December of 1991 to July 31, 2000 the Cleveland Clinic Foundation has placed
      240 mechanical support devices. These include 173 HeartMate devices of the
      Pneumatic or Vented Electric models, 56 Novacors, and 11 Thoratecs. Patients
      placed on mechanical support potentially proceed through six phases of support.
      This begins with the evaluation process and progresses through the perioperative
      phase, the intensive care phase, the regular nursing floor phase, discharge, and
      transplantation. We have developed a specialized team to care for this patient
      population. As a result, the nursing and psychosocial care of patients on
      mechanical support has advanced over years of experience. We have been able to
      identify specific nursing and psychosocial issues that develop through the phases
      of support. Becoming aware of these issues will assist in a successful outcome
      for the patient.

PMID- 11824667
TI  - Update on the total artificial heart.
AB  - There has been a quest for an artificial organ that can replace the heart for
      decades. Remarkable advances were made in the second half of the twentieth
      century in the fields of medicine and engineering that led to the development of
      several devices with the intention of totally replacing the human heart. Some of
      these devices, like the Jarvik artificial heart, were utilized initially as a
      permanent replacement for the failing heart. It became more successful as a
      bridge to heart transplantation (BTT) in the years that followed its
      introduction. Currently the CardioWest total artificial heart (TAH) is the only
      device in clinical use with the intention of bridging patients to heart
      transplantation. Two new TAHs are being developed with the intention of being
      used as an alternative to transplantation (ATT) or on a permanent basis. The next
      100 years will bring revolutionary new designs and advances in the field of end
      stage heart disease that may only be ideas at the present time.

PMID- 11824668
TI  - Is phrenic nerve dysfunction after cardiac surgery related to internal mammary
      harvesting?
AB  - BACKGROUND: Although many surgeons feel that internal mammary artery (IMA)
      harvesting is a risk factor for phrenic nerve dysfunction (PND) following
      coronary artery bypass grafting surgery (CABG), objective data confirming this
      are lacking. We sought to compare two groups of cardiac surgical patients to
      determine if an association exists between IMA harvesting and PND following CABG.
      METHODS: Using inpatient medical records and chest radiographs, we performed a
      retrospective analysis of 25 consecutive CABG patients and 25 consecutive valve
      procedure patients in order to compare the incidence of PND following cardiac
      surgery with and without IMA harvesting. RESULTS: Two patients were excluded.
      Thirty-one patients underwent IMA harvesting as part of their procedure, of whom
      42% had PND evidenced on postextubation chest X-ray. Seventeen patients did not
      have IMA harvesting, and the incidence of PND in this group was 12% (p = 0.05).
      Both groups were similar in preoperative variables and operative techniques.
      CONCLUSION: This study suggests IMA harvesting is indeed a risk factor for PND
      following CABG.

PMID- 11824669
TI  - Can statins reduce the inflammatory response to cardiopulmonary bypass? A
      clinical study.
AB  - OBJECTIVE: In addition to lowering lipid levels, statins might reduce leukocyte
      endothelial cell interactions. Therefore, we assessed whether this effect could
      limit the inflammatory response to cardiopulmonary bypass (CPB) in cardiac
      surgical patients. METHODS: Twenty patients undergoing valve or coronary
      operations with tepid (34 degrees C) CPB were randomized to receive an oral dose
      of atorvastatin (40 mg the evening before and 40 mg the morning of surgery) or to
      serve as controls. Pre- and post-CPB blood samples were assayed for neutrophil
      CD11b surface adhesion molecule and oxidative burst. Plasma levels of
      interleukins 6 and 8, P-selectin, soluble intercellular adhesion molecule-1, and
      lactoferrin were measured by enzyme-linked immunosorbent assay (ELISA). In
      addition, right atrial biopsies were taken before and at the end of CPB, and
      processed for the expression of the transcription nuclear factor-kappa B (NF
      kappaB). RESULTS: The two groups did not differ with regard to pre- and
      intraoperative data. Except for P-selectin, postbypass values of all markers
      significantly increased over baseline values, but atorvastatin therapy failed to
      attenuate the magnitude of this increase. In the two groups, the expression of NF
      kappaB significantly (p = 0.004) increased over baseline without group effect.
      Postoperative clinical outcomes did not differ either between the two groups.
      CONCLUSION: These data show that acute preoperative statin therapy fails to limit
      the inflammatory response to CPB; however, the data also document a major
      upregulation of NF-kappaB during cardiac operations, thereby providing a sound
      rationale for interventions targeted at inactivating this key component of the
      inflammatory cascade.

PMID- 11824670
TI  - Redo composite valve graft replacement.
AB  - BACKGROUND: Redo composite valve graft replacement remains a challenging problem,
      that may lead to increased surgical mortality. METHODS: In our experience from
      September 1976 through December 1999, eight consecutive patients (seven men and 1
      woman) underwent eight redo composite valve graft replacements. The mean age at
      reoperation was 43.1 years (range 31 to 51 years). Seven patients had stigmata of
      Marfan's syndrome. Reoperation was indicated for pseudoaneurysm formation in five
      patients, coronary ostial aneurysms in two patients, and active fungal
      endocarditis in one patient. Previous root replacement had been performed in all
      eight patients using a composite mechanical valve. The techniques used at
      previous procedures were the Bentall technique in seven and Carrel's button
      technique in one. The mean interval between primary root replacement and redo
      root replacement was 10 years (range 2 to 18 years). The patient with active
      fungal endocarditis having a stuck valve was subjected to emergency operation.
      RESULTS: The techniques used at the reoperations included Carrel's button
      technique in five patients, the interposition technique (Phieler) in two
      patients, and Cabrol's technique in one patient. Aortic arch aneurysm repair was
      performed in five patients. There were two hospital deaths (2 [25%] of 8). One
      patient died on postoperative day 1 with low cardiac output and the other
      suffered a sudden cardiac arrest on postoperative day 14. The mean follow-up was
      34.6 months (range 1 to 85 months). There was one late death. The cause of death
      was multiple organ failure due to recurrence of fungal endocarditis 6 months
      after redo composite and total arch replacement. CONCLUSION: Redo composite graft
      replacement can be accomplished with lower early mortality, and therefore, this
      operation should not be delayed given the appropriate clinical circumstances.
      Many causes of failure of composite valve graft replacement can be avoided if the
      appropriate surgical technique is chosen.

PMID- 11824671
TI  - Results of aortic arch repair with hypothermic circulatory arrest and retrograde
      cerebral perfusion.
AB  - BACKGROUND: Repair of aortic arch pathology is reliably performed with
      hypothermic circulatory arrest, but the best method of brain protection is
      controversial. METHODS: We reviewed a consecutive series of 67 patients who had
      aortic arch repair with hypothermic circulatory arrest. Retrograde perfusion of
      arterial blood into the superior vena cava (SVC) during systemic arrest was used
      in 87%. Average age was 65 years. Acute dissection was present in 25%. Average
      circulatory arrest time was 37 minutes, and average temperature 17.7 degrees C.
      RESULTS: Hospital mortality was 1.5%. Strokes occurred in 4.5%. Temporary
      neurological dysfunction occurred in 16%. Multivariate logistic regression
      analysis showed that acute dissection was the only independent predictor of the
      combined risk of stroke and temporary neurological dysfunction (odds ratio 8.5).
      Duration of circulatory arrest and patient age were not risk factors for adverse
      neurological outcome. CONCLUSION: Continuous arterial perfusion of the SVC during
      hypothermic circulatory arrest provides excellent cerebral protection for aortic
      arch repair. Acute dissection is an independent risk factor for adverse
      neurological outcome. Arrest time is not a predictor of neurological dysfunction.

PMID- 11824672
TI  - Application of pusher in mini-invasive patent ductus arteriosus ligation.
AB  - The possibility of a residual shunt is a major drawback to current minimally
      invasive procedures for the treatment of patent ductus arteriosus (PDA). From
      April 1997 to October 1999, 30 patients (10 males, 20 females) underwent PDA
      ligation by a modified technique that uses a pusher for securing the ligate of
      PDA via posterolateral minithoracotomy at our hospital. No complication or
      mortality occurred. Postoperative echocardiography also revealed no residual
      shunt. In this article, we introduce this simple, safe procedure for PDA
      ligation.

PMID- 11824673
TI  - A novel synthetic sealant to treat air leaks at cardiac reoperation.
AB  - PURPOSE: Pulmonary injury with resultant air leak is common at cardiac
      reoperation. Sequelae of this complication include prolonged chest tube drainage
      and time to ambulation, extended hospitalization and increased costs, and
      mediastinitis. The purpose of this study was to test the efficacy of a new
      synthetic absorbable sealant at treatment air leaks occurring at cardiac
      reoperation. PATIENTS AND METHODS: Fifteen patients having cardiac reoperation
      had lung injuries repaired with FocalSeal-L Sealant (Focal, Inc., Lexington, MA).
      Mean age was 61+/-15 years, and mean interval from the previous to the current
      operation was 44+/-38 months. RESULTS: In all patients, FocalSeal-L Sealant was
      successful at sealing intraoperative air leaks. Postoperatively, 73% of patients
      had no air leak. Four patients (27%) developed a recurrent air leak, three on
      postoperative day 1 and one on postoperative day 2. In three of these patients,
      the air leak sealed within 3 days. In the fourth patient, an immunosuppressed
      heart transplant recipient with mediastinitis, the air leak never sealed; that
      patient died of sepsis after an omental flap failed to control the air leak. In
      patients without air leak, chest tubes were removed on postoperative day 1 (9
      patients) or 2 (1 patient). CONCLUSION: This novel synthetic sealant prevents
      postoperative air leaks in the majority of patients suffering lung injury at
      cardiac reoperation.

PMID- 11824674
TI  - Acute right ventricular failure during aortic root replacement: intraoperative
      diagnosis and treatment.
AB  - The scope of this article is to report on a patient who underwent a Bentall
      procedure for type A aortic dissection. Right ventricular (RV) failure developed
      immediately after completion of the operation. The etiology was determined by
      using transit time flow measurement (TTFM), an ultrasound-based technique which
      demonstrated the absence of blood flow to the right coronary artery. This allowed
      for early and effective treatment, which was followed by a successful outcome.

PMID- 11824675
TI  - Minimally invasive valve surgery.
AB  - BACKGROUND: Cardiac surgery has been the last area of clinical surgery to adopt
      and embrace minimally invasive surgical techniques. Since the onset of arterial
      embolectomy in 1965, arthroscopic knee surgery performed in 1975 and laparoscopic
      cholecystectomy in 1985, huge advances in videoscopic, thorascopic and small
      incision surgery has taken place in all specialties which now allow change in the
      traditional approaches to cardiac valve surgery. In 1996, the Brigham and Women's
      Hospital, along with other units, began minimally invasive cardiac valve surgery
      for patients who had isolated valve pathology without coronary disease. Our
      experience now totals 689 patients, including 353 minimally invasive mitral valve
      repair/replacements and 336 minimally invasive aortic valve replacements,
      including root replacement and reoperations. METHODS: This new operative approach
      involves smaller incisions, the mandatory use of transesophageal echocardiogram
      for the monitoring of operation quality and air removal, newer perfusion
      techniques and some modifications in the standard valve repair/replacement
      techniques. With this blending of TEE, better perfusion techniques and new
      exposure, the safety and quality of valve operations by these techniques have
      been excellent. RESULTS AND CONCLUSION: The operative mortality is equal to (AVR)
      or less than (MVP) conventional open sternotomy cases and there is a shorter
      length of stay in the ICU and post-ICU, leading to a lower cost than conventional
      procedures. There are also less blood transfusions, atrial fibrillation and
      posthospital rehabilitation requirements, and patients have indicated that there
      is a faster return to normality over the conventional operative approaches. This
      brief report summarizes our experience from July, 1996 to January 2001.

PMID- 11824676
TI  - A case study comparing static and spatially explicit ecological exposure analysis
      methods.
AB  - Exposure to chemical contaminants must be estimated when performing ecological
      risk assessments. A previous article proposed a habitat area and quality
      conditioned population exposure estimator, E[HQ]P, and described an individual
      based, random walk, Monte Carlo model (SE3M) to facilitate calculation of E[HQ]P.
      In this article, E[HQ]P was compared with exposure estimates from a baseline risk
      assessment that evaluated mink and great blue heron exposure to fluoride at a
      federal Superfund site. Calculation of E[HQ]P took into consideration a
      receptor's forage area, movement behavior, population size, and the areal extent
      and quality of suitable habitat. The baseline assessment used four methods that
      did (total and unit Tier 2) and did not (total and unit Tier 1) consider habitat
      area or quality; where "total" included all exposure units on site and "unit"
      only a given exposure unit. Total Tier 1 estimates were consistently higher than
      E[HQ]P (e.g., 169.1 mg/kg x d versus 21.6 mg/kg x d). Risk managers using total
      Tier 1 results for decision making would be unlikely to underestimate exposure;
      however, implementability of correspondingly lower remedial objectives could be
      challenging. Unit Tier 1 estimates were higher (e.g., 96.5 mg/kg x d versus 61.6
      mg/kg x d) or lower (e.g., 3.5 mg/kg x d versus 51.1 mg/kg x d) than E[HQ]P
      depending on variations in landscape features. Total Tier 2 and E[HQ]P estimates
      were similar (e.g., 20.7 mg/kg x d versus 21.6 mg/kg x d) when an ecologically
      questionable average exposure was assumed. Unit Tier 2 estimates were
      consistently well below E[HQ]P (e.g., 17.8 mg/kg x d versus 61.6 mg/kg x d) when
      an average exposure was not assumed. Risk managers using unit Tier 1 or 2 results
      could be basing their decisions on potentially large underestimates of exposure.
      By forgoing average exposure assumptions, and explicitly addressing landscape
      heterogeneity, SE3M appears capable of yielding exposure estimates that are not
      as potentially misleading to risk managers as those produced with traditional
      averaging methods.

PMID- 11824677
TI  - Ecological risk-benefit analysis of a wetland development based on risk
      assessment using "expected loss of biodiversity".
AB  - Ecological risk from the development of a wetland is assessed quantitatively by
      means of a new risk measure, expected loss of biodiversity (ELB). ELB is defined
      as the weighted sum of the increments in the probabilities of extinction of the
      species living in the wetland due to its loss. The weighting for a particular
      species is calculated according to the length of the branch on the phylogenetic
      tree that will be lost if the species becomes extinct. The length of the branch
      on the phylogenetic tree is regarded as reflecting the extent of contribution of
      the species to the taxonomic diversity of the world of living things. The
      increments in the probabilities of extinction are calculated by a simulation used
      for making the Red List for vascular plants in Japan. The resulting ELB for the
      loss of Nakaikemi wetland is 9,200 years. This result is combined with the
      economic costs for conservation of the wetland to produce a value for the
      indicator of the "cost per unit of biodiversity saved." Depending on the
      scenario, the value is 13,000 yen per year-ELB or 110,000 to 420,000 yen per year
      ELB (1 US dollar = 110 yen in 1999).

PMID- 11824678
TI  - The risk of groundling fatalities from unintentional airplane crashes.
AB  - The crashes of four hijacked commercial planes on September 11, 2001, and the
      repeated televised images of the consequent collapse of the World Trade Center
      and one side of the Pentagon will inevitably change people's perceptions of the
      mortality risks to people on the ground from crashing airplanes. Goldstein and
      colleagues were the first to quantify the risk for Americans of being killed on
      the ground from a crashing airplane for unintentional events, providing average
      point estimates of 6 in a hundred million for annual risk and 4.2 in a million
      for lifetime risk. They noted that the lifetime risk result exceeded the commonly
      used risk management threshold of 1 in a million, and suggested that the risk to
      "groundlings" could be a useful risk communication tool because (a) it is a man
      made risk (b) arising from economic activities (c) from which the victims derive
      no benefit and (d) exposure to which the victims cannot control. Their results
      have been used in risk communication. This analysis provides updated estimates of
      groundling fatality risks from unintentional crashes using more recent data and a
      geographical information system approach to modeling the population around
      airports. The results suggest that the average annual risk is now 1.2 in a
      hundred million and the lifetime risk is now 9 in ten million (below the risk
      management threshold). Analysis of the variability and uncertainty of this
      estimate, however, suggests that the exposure to groundling fatality risk varies
      by about a factor of approximately 100 in the spatial dimension of distance to an
      airport, with the risk declining rapidly outside the first 2 miles around an
      airport. We believe that the risk to groundlings from crashing airplanes is more
      useful in the context of risk communication when information about variability
      and uncertainty in the risk estimates is characterized, but we suspect that
      recent events will alter its utility in risk communication.

PMID- 11824679
TI  - Public response to the Tokai nuclear accident.
AB  - This article discusses the influence of the September 30, 1999 nuclear accident
      in Tokai village (Japan) on the public's attitudes toward nuclear power in Japan.
      The data used in this report were taken from the results of two surveys conducted
      mainly to measure the attitudes of the Japanese public with regard to the use of
      nuclear power in Japan. The first survey was done before the accident in District
      23 in Tokyo and also in Osaka and Nagoya. The second survey, which took place
      after the accident in District 23 in Tokyo and in Osaka and Nagoya, also included
      residents in a number of other cities of various sizes throughout Japan. The
      results of the two surveys showed that (1) acceptability of and trust in nuclear
      power operation had decreased, (2) perceived accident likelihood and public
      interest had significantly increased, and (3) there had been neither significant
      nor even a small change in the public's self-rated knowledge about nuclear power
      or their distrust of the government. The results also showed that the ratio of
      nuclear power generation opponents to total respondents had considerably
      increased (7% to 23%) whereas nuclear power generation supporters had moderately
      decreased (1% to 12%).

PMID- 11824680
TI  - Shared values, social trust, and the perception of geographic cancer clusters.
AB  - Extensive scientific investigations often fail to identify specific carcinogens
      that have caused geographic clusters of cancer cases. In many such examples,
      public health officials and other experts have concluded that the cluster is not
      the result of a particular local environmental condition. Despite this conclusion
      by experts, concerned members of local communities often persist in believing
      that the cancer cluster was not random. The present study accounts for the
      persistence of this belief on the basis of two factors: (a) the tendency of the
      human mind to identify patterns (and causes), rather than randomness; and (b) a
      lack of social trust in public health experts. It was expected that perceived
      shared values evoke social trust. Individuals who conclude that public health
      experts share their values should be more likely to accept the experts'
      conclusion that a cancer cluster reflects randomness, not a particular local
      cause. Individuals who trust authorities should be more inclined than individuals
      not having trust to accept that a geographic cluster of cancer cases is a
      coincidence. Data from Swiss students (N = 334) supported these expectations.
      Additionally, significant gender differences were observed. Females had less
      trust in authorities and perceived the cancer cluster as less likely to be a
      result of pure chance than did males. Practical implications of the results are
      discussed.

PMID- 11824681
TI  - Correlates of hazard education programs for youth.
AB  - Virtually no research has examined the hypothesized benefits of hazard education
      programs for youth in helping to increase community resilience. This exploratory
      study examined the role of these programs in helping to increase child and family
      resilience to a range of future hazards. Various aspects of hazards programs were
      examined in relation to a wide range of child- and parent-reported hazard
      adjustments in a sample of 560 schoolchildren. Additional factors assessed
      included childrens' risk perceptions, knowledge of response-related protective
      activities, and hazard-related emotional factors. Overall, the results supported
      the role of hazards education programs in increasing hazard adjustments in the
      home. The findings also supported various aspects of education program
      involvement as being related to more realistic risk perceptions, increased
      knowledge, and increased interaction with caregivers. Analyses identified the
      following features of these programs as being particularly important: provision
      of specific knowledge (e.g., an emergency management perspective); multiple
      program involvement over time; and, importantly, promotion of increased
      interaction between children and parents. Overall, findings supported the idea
      that hazards education programs for youth provide one gateway through which
      communities can increase their resilience to the effects of a major hazardous
      event. Findings also provided an initial foundation for further research in this
      emerging area.

PMID- 11824682
TI  - Testing a structured decision approach: value-focused thinking for deliberative
      risk communication.
AB  - Public participation is now part of many decision making processes for managing
      environmental and technical risks. This article describes a test of a strategy to
      improve the quality of public input by combining themes from risk communication
      with the prescriptive decision process of value-focused thinking. It was
      hypothesized that participating in a structured, value-focused risk communication
      approach would lead people to make more thoughtful, better informed, and hence
      higher quality decisions by helping them to consider and discuss a wider array of
      decision-relevant issues and address key value trade-offs. It is also anticipated
      that utilizing a value-focused decision structure would make participants feel
      more comfortable with their decisions; more satisfied that their selected
      alternative reflected their key concerns; and, in the end, more satisfied with
      their decisions. To test these hypotheses, six groups comprised of 7 to 10 people
      participated in conventional "alternative-focused" risk communication workshops
      and eight groups participated in similar "value-focused" workshops. All workshops
      dealt with the management of risks to riverine salmon habitat from hydroelectric
      electricity generation. The results provided support for the hypotheses: the
      value-focused decision structure led to more thoughtful and better informed risk
      management decisions.

PMID- 11824683
TI  - Application of monitoring data for Giardia and Cryptosporidium to boil water
      advisories.
AB  - Despite the problems associated with analyzing water samples for Giardia cysts
      and Cryptosporidium oocysts, the data can be very useful if their strengths and
      weaknesses are understood. Two municipalities in northern Ontario, Temagami and
      Thunder Bay, both issued boil water advisories for Giardia contamination. Data
      from these two cities are compared to show that only one municipality experienced
      a real outbreak, whereas the other did not. The concentration of Giardia cysts
      was much higher than background during the outbreak at Temagami, and the
      postoutbreak concentrations of cysts were very similar to the long-term average
      cyst concentration at Thunder Bay. The waterborne outbreak of giardiasis at
      Temagami was characterized by consistent positive results from water samples,
      concentrations two to three orders of magnitude higher than normal, and an
      obvious increase in the number of cases of giardiasis in the population. No
      outbreak was experienced at Thunder Bay, but a boil water advisory (BWA) was set
      in place for more than a year on the basis of a single sample from Loch Lomond in
      which only two cysts were detected but the sample equivalent volume was low. This
      gave the impression of a sudden increase in concentration, but 39 of 41
      subsequent samples were negative. Additional factors that led to a BWA at Thunder
      Bay are described, and recommendations are presented to help determine when a BWA
      is necessary and when it should be rescinded.

PMID- 11824684
TI  - Poliovirus surveillance by examining sewage water specimens: studies on detection
      probability using simulation models.
AB  - Efficiency of environmental surveillance of poliovirus circulation was studied
      using simulation models. First, three transmission models were defined for
      describing different scenarios of poliovirus infections in a large unstructured
      population. Second, environmental factors, such as the total volume of the sewage
      network and losses of viruses, were modeled for computing the virus output at the
      sewage sampling site. Third, the effect of sampling and laboratory procedures was
      accounted for in the probability of detection, given the amount of polioviruses
      in a specimen. The simulation model can be used for theoretical assessments of
      the likely efficiency of environmental surveillance, compared with acute flaccid
      paralysis (AFP) surveillance. Under reasonable assumptions in a vaccinated
      population, the AFP surveillance can be outperformed if the poliovirus outbreak
      is not large. However, this depends on the assumed case-to-infection ratio and on
      the sampling frequency of the sewage water specimens. Increasing the latter will
      lead to a higher detection probability, which will further enhance the method
      based on environmental surveillance.

PMID- 11824685
TI  - Modeling virus inactivation on salad crops using microbial count data.
AB  - Microbial counts of the persistent Bacteroides fragilis bacteriophage B40-8 from
      a virus decay experiment conducted under glasshouse conditions were used to model
      the decay of viruses on wastewater-irrigated lettuce and carrot crops. The
      modeling approach applied gave specific consideration to the discrete nature of
      microbial count data. The experimental counts were best fit by a negative
      binomial distribution indicating highly dispersed distribution of viruses on
      lettuce and carrot crops following irrigation with wastewater. In addition, there
      was evidence for biphasic inactivation of viruses, signifying the presence of a
      persistent subpopulation of viruses that decayed slowly, resulting in virus
      accumulation on the crop surface over subsequent irrigations. Maximum likelihood
      estimates of initial and persistent subpopulation inactivation rates were 2.48
      day(-1) and 0.51 day(-1) for lettuces and 0.84 day(-1) and 0.046 day(-1) for
      carrots. Maximum likelihood estimates of the persistent virus subpopulation size
      were 0.12% and 2% for lettuce and carrots, respectively.

PMID- 11824687
TI  - The genomic revolution: what does it mean for risk assessment?

PMID- 11824686
TI  - A GIS-based framework for hazardous materials transport risk assessment.
AB  - This article presents a methodology for assessment of the hazardous materials
      transport risk in a multicommodity, multiple origin-destination setting. The
      proposed risk assessment methodology was integrated with a Geographical
      Information System (GIS), which made large-scale implementation possible. A GIS
      based model of the truck shipments of dangerous goods via the highway network of
      Quebec and Ontario was developed. Based on the origin and destination of each
      shipment, the risk associated with the routes that minimize (1) the transport
      distance, (2) the population exposure, (3) the expected number of people to be
      evacuated in case of an incident, and (4) the probability of an incident during
      transportation was evaluated. Using these assessments, a government agency can
      estimate the impact of alternative policies that could alter the carriers' route
      choices. A related issue is the spatial distribution of transport risk, because
      an unfair distribution is likely to cause public concern. Thus, an analysis of
      transport risk equity in the provinces of Quebec and Ontario is also provided.

PMID- 11824688
TI  - A framework to guide thinking and analysis regarding climate change policies.
AB  - The potential impacts from climate change, and climate change policies, are
      massive. Careful thinking about what we want climate change policies to achieve
      is a crucial first step for analysts to help governments make wise policy choices
      to address these concerns. This article presents an adaptive framework to help
      guide comparative analysis of climate change policies. The framework recognizes
      the inability to forecast long-term impacts (due in part to path dependance) as a
      constraint on the use of standard policy analysis, and stresses learning over
      time as a fundamental concern. The framework focuses on the objectives relevant
      for climate change policy in North America over the near term (e.g., the next 20
      years). For planning and evaluating current climate policy alternatives, a
      combination of fundamental objectives for the near term and proxy objectives for
      characterizing the state of the climate problem and the ability to address it at
      the end of that term is suggested. Broad uses of the framework are discussed,
      along with some concrete examples. The framework is intended to provide a basis
      for policy analysis that explicitly considers the benefits of learning over time
      to improve climate change policies.

PMID- 11824689
TI  - Therapeutic jurisprudence: a multidisciplinary conference.

PMID- 11824690
TI  - Proposition 36: issues and challenges.
AB  - A discussion of California's Substance Abuse and Crime Prevention Act of 2000
      (Proposition 36) and how it represents a paradigm shift from incarceration to
      treatment and collaboration.

PMID- 11824691
TI  - Exploring the opportunities of Proposition 36.
AB  - This article must be considered a work-in-progress. The California Society of
      Addiction Medicine seeks to briefly enumerate some guiding principles for initial
      consideration. It is the Society's hope that the issues presented here can
      promote further discussion and planning in collaboration with our colleagues in
      the criminal justice system, the community of California treatment providers, and
      other social service agencies, and in future consultations with experts at the
      National Institutes of Health and other relevant research and treatment agencies
      in California, Washington, and elsewhere.

PMID- 11824692
TI  - California Collaborative Center for Substance Abuse Policy Research: a history
      and update.
AB  - The California Collaborative Center for Substance Abuse Policy Research is
      engaged in policy research, training, and information dissemination on substance
      abuse policy in and for the state of California. As such it is a cosponsor of the
      recent Therapeutic Jurisprudence conference with Haight Ashbury Free Clinics. The
      following recoups a presentation made by Richard B. Seymour on behalf of Center
      codirector Carroll Estes at that conference on the nature, history, and future
      priorities of the Center.

PMID- 11824693
TI  - Prevention, community services and Proposition 36.
AB  - The Prevention Panel of the Therapeutic Jurisprudence conference presented
      several examples of community services and prevention policies that should be
      brought into the mix of services and supports for Prop 36 and for other court
      diversion programs. This article summarizes those presentations and suggests how
      they might be put to work as effective alternatives to incarceration.

PMID- 11824694
TI  - The impact of criminal justice institutions on substance abuse treatment.
AB  - This article explores drug treatment from a community provider perspective.
      Specifically, it examines the impact of criminal justice institutions on
      substance abuse treatment: the gray zone where jurisprudence meets the
      therapeutic.

PMID- 11824695
TI  - Therapeutic jurisprudence: judicial and corrections panel.
AB  - Innovative therapeutic initiatives for the treatment of persons with substance
      abuse problems have been implemented in the criminal justice systems of
      California and Arizona. Judicial perspectives and reflections on these programs
      reveal the multiple issues inherent in innovation and day-to-day operations, from
      collaboration to implementation, including attitudinal shifts, resource
      allocation, client issues, and the changing role of judges who practice
      therapeutic jurisprudence. A pioneering program of treatment for dual disorders
      among male offenders addresses multiple issues in the provision of psychological
      services in a forensic setting in California.

PMID- 11824696
TI  - Drug court effectiveness: a review of California evaluation reports, 1995-1999.
AB  - Over the past two decades, drug courts have emerged as a viable alternative for
      addressing drug cases within the criminal justice system. In California, the Drug
      Court Partnership Program (DCPP) was created in 1998 and has supported and funded
      the development of drug courts throughout the State. This article reports on a
      review of California drug court evaluations through January 2000 conducted as
      part of an evaluation of the California DCPP. A total of 23 evaluations were
      collected. Seventeen were reviewed in detail, and six were excluded because they
      were internal reports rather than evaluations. A standardized review process was
      initiated which led to a scored rating of the evaluation reports. Results of this
      review support previous findings that drug court participants may experience
      reduced rearrest rates by 11% to 14% compared to nonparticipants. The largest
      reduction in rearrest rates appears among graduates. The graduation rates were
      between 19% and 54%. Costs and savings associated with drug courts were discussed
      but no conclusions were possible based on the findings from these evaluations.
      The evaluation of the effectiveness of drug courts presents unique challenges.
      This review concludes with a discussion of evaluation methods (e.g. standardizing
      rate calculations, term definitions) that would strengthen drug court research.

PMID- 11824697
TI  - Drug use, street crime, and sex-trading among cocaine-dependent women:
      implications for public health and criminal justice policy.
AB  - The linkages between the sex-for-crack exchanges, prostitution, and rising rates
      of HIV and other sexually transmitted diseases among cocaine-dependent women have
      been well documented. As crack began to disappear from the headlines during the
      1990s, however, it was assumed by many that crack had fallen on hard times in the
      street drug culture. Within this context, this article examines the extent to
      which crack has remained primary in the culture of cocaine-dependent women. Data
      are drawn from a study of 708 cocaine-dependent women in Miami, Florida, during
      the years 1994 to 1996, and qualitative data gathered during 1998 and 1999 in the
      same field areas. Analyses focus on drug use, criminality and HIV/AIDS risk
      behaviors. Implications for policy alternatives in criminal justice and public
      health approaches for assisting this population are discussed.

PMID- 11824698
TI  - Drug treatment effectiveness: African-American culture in recovery.
AB  - African-Americans are overrepresented among drug abusers in the United States
      when compared to European-Americans, and have lower rates of recovery from drug
      addiction after treatment. There has been no comprehensive research to date to
      specifically explain either this overrepresentation or lower rates of recovery
      among African-Americans. In this article, it is suggested that one reason for
      this lack of attention is due to the failure of drug abuse treatment providers
      and researchers to see race as a cultural rather than physical phenomenon. The
      point is made that cultural factors are intrinsic to successful efforts to
      address drug abuse among African-Americans. Several historic African-American
      coping strategies are outlined and shown to be powerful factors in client
      addictive behavior and barriers to recovery. Through case studies of clients who
      were successful in their effort to recover, the necessity to address cultural as
      well as personal issues is shown to be vital to successful recovery among African
      Americans.

PMID- 11824699
TI  - Pharmepena-Psychonautics: Human intranasal, sublingual and oral pharmacology of 5
      methoxy-N,N-dimethyl-tryptamine.
AB  - Summarized are psychonautic bioassays (human self-experiments) of pharmepena-
      crystalline 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT; O-Me-bufotenine), at
      times combined with crystalline beta-carbolines (harmaline or harmine). These
      substances were administered via intranasal, sublingual and oral routes, by way
      of pharmacological modeling of diverse South American shamanic inebriants
      (principally the snuffs epena/nyakwana, prepared from barks of diverse species of
      Virola.) Intranasal, sublingual and oral psychoactivity of 5-MeO-DMT, and the
      1967 Holmstedt-Lindgren hypothesis of the parica-effect--intranasal potentiation
      of tryptamines by concomitant administration of monoamine-oxidase-inhibiting
      (MAOI) beta-carbolines from stems of Banisteriopsis caapi admixed with the snuffs
      -have been confirmed by some 17 psychonautic bioassays. Salient phytochemical and
      psychonautic literature is reviewed.

PMID- 11824700
TI  - Overdose of 2.3 grams of intravenous methamphetamine: case, analysis and patient
      perspective.
AB  - The patient-reported toxicity of an overdose of intravenous methamphetamine is
      described. The authors report the case of a 34-year old man who inadvertently
      injected himself with approximately 2.3 grams of methamphetamine. The patient
      reported disorientation, hallucinations, hyperthermia, photophobia, orthostasis
      and extreme ataxia. He recovered in seven days without apparent sequelae. The
      case demonstrates the unusual, temporary neurophysiologic consequences of high
      dose intravenous methamphetamine.

PMID- 11824702
TI  - Industrial buyers' perception of effective selling'.
AB  - The most fundamental aspect of commerce is interaction between buyers and
      sellers. Accordingly, the psychological study of selling techniques can be
      considered as old as trade. This study investigated two categories of selling
      techniques composed of 17 objection-addressing and 13 sale-dosing strategies.
      Reported are survey responses from 242 industrial buyers, frequent targets of
      selling techniques, who were asked to identify which technique from each category
      they associated with salespersons' effective selling behavior.

PMID- 11824701
TI  - Components of type A behavior and two-year prognosis of patients with acute
      coronary syndrome.
AB  - We investigated prospectively the relationship of Type A behavior and its
      subcomponents with cardiac mortality and recurrent nonfatal cardiac events in a 2
      yr. follow-up of 90 patients [69 men and 21 women, M age=56.4 yr., SD=8.4] after
      acute coronary syndrome. Type A behavior was assessed via the general Bortner
      Type A Index. Each patient completed the Bortner's scale before hospital
      discharge. During the first 2-yr. follow-up, there were 14 cardiac deaths among
      patients with myocardial infarction. 8 patients had recurrent cardiac events and
      were hospitalized, and 19 patients had an effort-induced angina pectoris.
      Patients with acute myocardial infarction who died during follow-up had a
      significantly lower Bortner score than patients with a secondary cardiac event.
      Bortner scores of patients with acute myocardial infarction who died indicated
      Type B behavioral patterns. Mortality was significantly higher in the patients
      classified as showing Type B (21.8%) behavior than in the patients classified as
      showing Type A (12.0%) behavior. Patients with a secondary cardiac event had more
      common Type A behavior patterns and higher Bortner scores than patients without a
      secondary cardiac event. The items on Bortner's scale "very competitive, ever
      rushed, tries to do too many things at once, fast in daily activities and
      expresses feelings" were inversely associated with cardiac deaths. These findings
      suggest that patients with acute coronary syndrome classified by scores on the
      Bortner scale as Type B behavior have a greater probability of death, and
      patients classified on the Bortner scale as Type A behavior have a greater
      probability of secondary cardiac events during follow-up. This finding may have
      implications for the treatment of patients with acute coronary syndrome. The
      inferior survival of patients with Type B personalities argues against attempts
      to modify Type A behavior in postinfarction patients.

PMID- 11824703
TI  - Remembering stories as a function of the medium of presentation.
AB  - Participants (50 women, 35 men) either watched, listened to, or read a piece of
      fiction for television. An immediate cued recall test showed, as predicted, that
      the group who read the piece remembered more than either of the other two groups.
      This confirms previous findings on adults that recall of material presented in
      the print medium is superior to that from audio-only and audio-visual
      presentation.

PMID- 11824704
TI  - Students' reports of athletic involvement as predictors of drinking: a pilot
      study.
AB  - 54 undergraduates' reports indicated that the amount of alcohol consumed per week
      did not differ among university athletes, intramural athletes, and non-athletes,
      but it was positively related to male gender and to reported smoking.

PMID- 11824705
TI  - Interrelations among gender-role conflict, typicality of occupations, and self
      esteem.
AB  - The present study was conducted with 549 women and men who were employed in
      gender-typical occupations or who were in vocational training, further
      qualification, or retraining for one of these job. We examined whether a gender
      typical occupation is related to gender-role conflicts of women and men in work
      settings and whether self-esteem moderates the experiences of conflict.
      Generally, we cannot confirm influence of gender-typical jobs on experience of
      conflict. The results, however, supply evidence for the fact that women
      experience higher gender-role conflicts than men in all occupations. Women and
      men of low self-esteem engaged in typically female occupations experience
      especially high gender-role conflict.

PMID- 11824706
TI  - An inventory to measure helplessness, hopelessness, and haplessness.
AB  - Using a sample of 69 undergraduates, scales were devised to measure helplessness,
      hopelessness, and haplessness and shown to have good reliability. Briefer scales
      were also developed whose scores were independent of one another in a factor
      analysis. Scores for 19 male and 50 female undergraduates on the 4-item scales of
      Helplessness and Hopelessness were associated with two different measures of
      depression, but scores on Hopelessness provided the stronger correlate.

PMID- 11824707
TI  - Development and validation of a multidimensional smoking behaviour questionnaire.
AB  - We administered a 42-item smoking behaviour questionnaire to 150 adult smokers
      (75 men and 75 women), 18 to 70 years old (M = 37.1 yr., SD = 12.2). A principal
      component analysis of their responses followed by varimax rotation yielded four
      factors accounting for about 52% of the total variance: dependence, social
      integration, regulation of negative affect, and hedonism. Some sociodemographic
      and dispositional characteristics of the smokers predict these four dimensions.
      The predictors of each smoking dimension are quite different for male and female
      smokers.

PMID- 11824708
TI  - Family and ability correlates of academic achievement.
AB  - Relationships were examined among family social status, family learning
      environments, intellectual ability, and the mathematics and word achievement of
      boys and girls. Data were collected from 516 (250 boys, 266 girls) 11-yr.-old
      Australian children and their parents. Analysis indicated that the relationships
      between the predictor and achievement variables varied for boys and girls and
      differed depending on the achievement measure being examined. Generally, the
      family and ability measures combined to have large associations with word scores,
      while intellectual ability was the only significant predictor of mathematics
      achievement.

PMID- 11824709
TI  - Episodes of pragmatic behaviors in parent-child interactions.
AB  - Pragmatic behavior, or the socially appropriate use of language, is important to
      parents of preschool children. In 1994 Becker noted several questions that still
      remain to be answered, including issues such as developmental changes in the
      pragmatic teaching of preschoolers and whether there are differences in the
      parents' goals for pragmatic teaching in private versus public interactions. The
      present study addressed these issues. 29 parent-child dyads were videotaped for
      30 min. Transcripts were coded for episodes of pragmatic behavior that occurred
      in the dyadic interaction. Analysis indicated that pragmatic behaviors across the
      age groups largely focused on issues of what to say and how to say it. The
      teaching and use of pragmatic behaviors in public interactions is relatively
      important to parents of children between 2 1/2 and 4 years. The spontaneous use
      of pragmatic behaviors was the most common form of input (78% overall). Pragmatic
      behaviors were more often prompted with direct, as opposed to indirect, comments.
      Discussion focuses on a content analysis of the direct versus indirect prompts in
      the different age groups.

PMID- 11824710
TI  - Predicting murder rates of police and civilians by each other.
AB  - For 1960-1992, while divorce rates predicted the general homicide rates, neither
      divorce nor unemployment rates predicted the rates with which police killed
      civilians or civilians killed police.

PMID- 11824711
TI  - Caffeine consumption questionnaire: a standardized measure for caffeine
      consumption in undergraduate students.
AB  - Undergraduate students (N=691) were given the 1992 Caffeine Consumption
      Questionnaire of Landrum and provided information on age, sex, and year in
      school. A subset (n = 168) of those completing the questionnaire were also given
      the Morningness-Eveningness Questionnaire of Horne and Ostberg. Analysis
      indicated that the average intake of caffeine was roughly 1,600 mg, i.e., a range
      from 13 mg to 21,840 mg per week. Older students consumed more caffeine than
      younger ones, and students with an Evening personality preference consumed more
      caffeine in the evening and nighttime hours than those with a Morning personality
      preference. These results are discussed in the context of other caffeine studies.
      Caffeine consumption is an important issue, and a consistent measurement system
      should be used by various researchers testing different populations.

PMID- 11824712
TI  - Association of alexithymic characteristics and posttraumatic stress responses
      following medical treatment for children with refractory hematological diseases.
AB  - Recent research has examined posttraumatic stress disorder (PTSD) following
      medical treatment for children with refractory hematological diseases such as
      leukemia. However, much remains unknown. This study examined the association of
      alexithymic characteristics on the manifestation of posttraumatic stress
      responses in 33 children with refractory hematological diseases. Of 33 children,
      27 (81.8%) exhibited posttraumatic stress responses following medical treatment
      for refractory hematological diseases. The frequency of posttraumatic stress
      responses was significantly higher than with children who experienced severe
      flood disaster. Also, the severity of posttraumatic stress responses was
      significantly stronger than for children who experienced severe flood disaster.
      Moreover, children with refractory hematological diseases were more likely to
      exhibit alexithymic characteristics. The alexithymic characteristics were
      significantly and positively correlated with avoidance and emotional numbing
      among posttraumatic stress responses. The results suggest the possibility that
      alexithymic characteristics may be predictive of the manifestation of avoidance
      and emotional numbing among posttraumatic stress responses following medical
      treatment for refractory hematological diseases.

PMID- 11824714
TI  - Differentiation of fluid, visual, and simultaneous cognitive tasks.
AB  - The constructs of fluid reasoning and spatial visualization (Horn, 1989) as well
      as the construct of simultaneous processing (Luria, 1966) have been tapped by
      various cognitive assessment batteries. In order to determine whether these
      constructs could be differentiated from one another, factor analyses of subtest
      scores from six cognitive tasks were conducted. Fluid reasoning, spatial
      visualization, and simultaneous processing emerged as separate factors in the
      analysis, supporting the hypothesis that these constructs can be differentiated
      in psychoeducational testing. These results extend the findings of a preliminary
      study which found factorial differentiation between fluid and simultaneous
      reasoning.

PMID- 11824713
TI  - Further evidence of reliability and validity for the driving anger expression
      inventory.
AB  - This study provided evidence of reliability and validity for the four scales of
      the Driving Anger Expression Inventory. Alpha reliabilities for scales ranged
      from .84 to .89. Measures of aggressive anger expression while driving (Verbal
      Aggressive Expression, Personal Physical Aggressive Expression, and Use of the
      Vehicle to Express Anger scales) correlated positively with each other and
      negatively with the Adaptive/Constructive Expression scale. Scores on the three
      aggressive forms of anger expression correlated positively with trait anger and
      measures of driving-related anger, aggression, and risky behavior, whereas scores
      on the Adaptive/Constructive Expression scale correlated negatively with these
      variables. Reports of aggressive and risky behavior correlated most strongly with
      the Use of the Vehicle to Express Anger scale. Forms of anger expression were
      minimally or uncorrelated with rated trait anxiety and reports of moving
      violations, close calls, and accidents. Findings replicated earlier findings and
      provided further evidence for the reliability and validity of the Driving Anger
      Expression Inventory.

PMID- 11824715
TI  - Different types of smiles and laughter in preschool children.
AB  - The relationship among morphologically different forms of smiling and laughter
      was examined. The participants were 19 Brazilian preschool children. Each child
      was observed a total of 60 min. in three 10-min. sessions on the playground and
      three 10-min. sessions in the classroom. Analysis suggests that the various forms
      of smiling do not simply express different intensities of a single emotion. A two
      dimensional structure was indicated by factorial analysis. The first dimension,
      which could be called playfulness-mock aggression, consisted of a broad smile and
      laughter. The second dimension, which could be called friendliness-appeasement,
      consisted of a closed and upper smile. The pattern of correlation found between
      expressive behaviors and both teacher's and peers' evaluations gives further
      support to the interpretation that smiling is an heterogeneous category.

PMID- 11824716
TI  - Evidence for the construct validities of the Beck Youth Inventories with child
      psychiatric outpatients.
AB  - To provide further information about the construct validities of the Beck Youth
      Inventories of Emotional and Social Impairment, these inventories were
      administered to 35 female and 65 male outpatients whose ages ranged from 7 to 12
      years and who were diagnosed with various psychiatric disorders. The Children's
      Depression Inventory was also administered, and the children were rated by a
      parent with the Conners' Parent Rating Scale-Revised: Short Form. The scores on
      the former inventory were more positively correlated with the scores on the Beck
      Youth Depression Inventory (r =.81, p<.001) than with scores on the four other
      Beck Youth Inventories, and those on the Conners Oppositional scale were
      comparably correlated with the scores on the Beck Youth Disruptive Behavior
      (r=.49, p<.001) and Anger (r=.41, p<.001) Inventories. These latter correlations
      were higher than those for scores on the Oppositional scale with the scores on
      the three other Beck scales.

PMID- 11824717
TI  - Reliability of the social skills rating system in a group of Iranian children.
AB  - The purpose of this study was to investigate reliability of the Social Skills
      Rating Systems of Gresham and Elliott for use in Iran. The sample consisted of
      304 students aged 6 to 12 years, selected from the elementary schools in Shiraz,
      Iran. Parents' and teachers' ratings of social skills and behavioural problems
      and self-rating of social skills were applied in this study. Pearson correlations
      between parents' and teachers' ratings were low to moderate. Correlations between
      social skills subdomains and behavioural problems subdomains were low to high.
      Cronbach coefficients alpha were satisfactory for the two subdomains.

PMID- 11824718
TI  - Perceptions of body hair on white women: effects of labeling.
AB  - This study examined 118 college students' perceptions of a White woman with body
      hair as a function of two different possible attributions. Participants reacted
      to a video of a young woman described as being either a feminist or as having a
      medical condition that hindered shaving. Students rated the woman on a variety of
      interpersonal traits. Analysis showed a main effect for body hair and for
      description but no interaction. The woman with body hair, whether for feminist or
      alternative reasons, was rated as significantly less friendly, moral, and
      relaxed, as well as more aggressive, unsociable, strong, nonconformist, dominant,
      assertive, independent, and in better physical condition than the same woman
      without body hair. Implications and directions for research are suggested.

PMID- 11824719
TI  - Posttraumatic stress disorder among survivors of a kamikaze attack.
AB  - 26 sailors who survived a Kamikaze attack during the battle for Okinawa in World
      War II were given two adapted forms of the Posttraumatic Stress Disorder
      Checklist-Civilian to assess the psychological reactions they had to the sinking
      of their ship. Depending on the assessment criteria used, their responses
      indicated significant stress reactions ranging from 8.3% to 44% of the sample.
      The findings provide evidence that a single combat experience can have lifelong,
      averse psychological effects.

PMID- 11824720
TI  - Diverse thinking-style preferences in a university course in mathematics.
AB  - At the University of Pretoria during 1999 the thinking-style preferences of three
      groups of students (ns = 50, 31, and 13) taking a first course in calculus were
      assessed using the Herrmann Brain Dominance Instrument. Analysis affirmed
      diversity in thinking-style preferences among the students and that the groups'
      scores represent a composite range of such preferences. Clearly, teachers of
      mathematics should be aware of and accommodate this diversity in instructional
      activities.

PMID- 11824721
TI  - Psychosocial and health-related characteristics of religious well-being.
AB  - This investigation examined the relationship between religions well-being and
      eight psychosocial and health-related characteristics. This study assessed the
      hypothesis that religious well-being is related to overall health. Participants
      were 462 college students at two separate colleges in the Pacific Northwest.
      Analysis showed those subjects scoring higher on the measure of religious well
      being scored lower on indices like loneliness and hopelessness and higher on self
      esteem. Alcohol and drug use also differed significantly between the high and the
      low, religious well-being groups.

PMID- 11824722
TI  - Physical symptoms, posttraumatic stress disorder, and healthcare utilization of
      women with and without childhood physical and sexual abuse.
AB  - For four groups of women: no abuse, physical abuse alone, combined sexual and
      physical abuse, and unclear about memories of abuse, we examined the associations
      between childhood sexual and physical abuse, chronic physical symptoms in
      adulthood, PTSD, and health care utilization. Of a randomly selected sample of
      600 adult femalc members of a health maintenance organization, 86 (14%) chose to
      participate. Women with a history of physical and sexual abuse in childhood
      reported significantly more cardiovascular, immune, musculoskeletal, neurologic,
      and reproductive symptoms than those without this history. While the
      Sexual/Physical Abuse group had the most chronic physical symptoms, medical
      visits, emergency room visits, prescriptions, and severe PTSD, the Unclear Memory
      group consistently ranked second on these same measures--higher than either
      Controls or the Physical Abuse group. Findings underscore the importance of
      screening for trauma history among patients seen in medical clinics, and the
      importance for psychotherapists of attending to patients' physical as well as
      psychological symptoms of childhood trauma.

PMID- 11824723
TI  - Note on Thorson and Powell: undertakers' sense of humor.
AB  - Recently Thorson and Powell reported in this journal that morticians scored
      significantly lower on a multidimensional sense of humor scale than another group
      of similarly aged men from other occupations. These findings differ markedly with
      some in 1991 from a 2-yr. ethnographic study conducted with morticians and
      funeral directors in four states regarding how they managed the stigma associated
      with their occupation.

PMID- 11824724
TI  - Training employees as a management attribute of successful companies.
AB  - This paper discusses training as an important attribute of successful companies
      and identified as characteristic of excellent Zimbabwean companies. Although
      confident this attribute contributes to successful performance by companies in
      which it is applied, it is possible that contributions could be more effective
      were all characteristics implemented collectively. However, the research suggests
      that training alone can offer significant improvement in employees' performance.

PMID- 11824725
TI  - Quality of life for children and suicide rates.
AB  - The quality of life in 1982 of children in nations of the world reported by
      Jordan in 1993 was positively associated with youth suicide rates only for males
      in 1982.

PMID- 11824726
TI  - An interpersonal analysis of Rorschach aggression variables in a normal sample.
AB  - This study investigated the relationship between Rorschach aggression variables
      and a self-report measure of interpersonal control and aggression (Structural
      Analysis of Social Behavior), rated for best and worst states, with 50 college
      students using forward stepwise regression analyses. Aggressive Movement (AG) was
      related to the report of self-attack for the best state ratings. The following
      findings were significant for the worst state ratings. AG was related to viewing
      the other as reacting as if attacked but the self as acting more affiliatively to
      the other. Aggressive Past (AgPast) was related to reacting to the other more
      submissively. A combined Aggressive Potential (AgPot)/Aggressive Content (AgC)
      variable was related to viewing the other as reacting less submissively and
      acting more dominantly. AgC was related to viewing the other as reacting less
      submissively. Methodological limitations are discussed, including potential
      problems regarding social desirability for the self-report aggression measure.

PMID- 11824727
TI  - Gun availability and use of guns for murder and suicide in Canada.
AB  - The accidental death rate from guns in Canada was associated with the percentage
      of guns used by suicides and on homicide victims except for elderly persons.

PMID- 11824728
TI  - Validity and reliability of the Japanese version of the Emotional Intelligence
      Scale among college students and psychiatric outpatients.
AB  - We examined the validity and reliability of the Japanese version of the Emotional
      Intelligence Scale in two samples of 267 college students and 398 psychiatric
      outpatients. Suitable validity and reliability of this scale were suggested by
      high correlations with scores on the NEO Personality Inventory, adequate internal
      consistency, and relatively high test-retest correlations. The Emotional
      Intelligence Scale seems suitable for both clinically distressed populations as
      well as comparative groups such as college students.

PMID- 11824729
TI  - Comparison of childhood problem behaviors in boys with subsequent schizophrenic,
      antisocial, and good adult outcomes.
AB  - Childhood problem behaviors for 145 boys seen in child guidance clinics were used
      to compare four adult outcome groups: antisocial men, schizophrenic subjects with
      good outcomes, schizophrenic subjects with poor outcomes, and subjects with good
      outcomes. Delinquent and aggressive factor scale scores distinguished the
      antisocial outcomes from the other groups. A preschizophrenic factor along with
      lower IQ separated schizophrenics with poor outcome from the others. Subjects
      with good outcomes had lower scores on factor scales, higher IQ, and less
      disturbed families. Schizophrenics with good outcomes were the most difficult to
      identify correctly.

PMID- 11824730
TI  - Content analysis of group work sessions in the context of an educational program
      for inpatient diabetes patients.
AB  - This study investigated the changes in emotions and attitudes of diabetic
      patients as observed in group work sessions linked to an inpatient diabetic
      educational program. Using content analysis of transcripts from Sessions 1 and 3
      of 8 selected groups (40 patients), in Session 1 negative emotions or attitudes
      such as anxiety, remorse, or self-blame, a lack of understanding of diabetes,
      along with a willingness to undertake self-care were frequently expressed. In
      Session 3, more positive emotions and attitudes towards self-care (willingness,
      specific plans, and resolutions), satisfaction, and relief or hope were
      frequently expressed. These results suggest that the patients participating in
      the group work sessions moved toward adaptation to diabetes, although the effects
      of the group work were not separated from those of the inpatient educational
      program.

PMID- 11824731
TI  - Fin-de-siecle ranking of important psychologists by a sample of undergraduate
      students enrolled in history of psychology.
AB  - 134 undergraduate students of the history of psychology from 1998 through 2000
      were requested to name three psychologists in order of importance, eminence, or
      influence within as well as outside the discipline of psychology. Salient was
      confirmation of Sigmund Freud as outranking other psychologists by a wide margin.

PMID- 11824733
TI  - Spiritual well-being and personality.
AB  - The hypothesis that High and Low Spiritual Well-being groups have different
      personality profiles was tested with 319 psychology undergraduates (132 men and
      187 women who completed the Revised NEO Personality Inventory and the Spiritual
      Well-being Scale for partial course credit. Univariate analyses of variance
      indicated that the High Spiritual Well-being group scored lower on Neuroticism
      and higher or Extraversion, Agreeableness. and Conscientiousness than the Low
      Spiritual Well-being group. Multivariate analysis of variance indicated that the
      two groups had significantly different personality profiles, supporting the
      hypothesis.

PMID- 11824732
TI  - Association of emotional intelligence with alexithymic characteristics.
AB  - We examined the association of emotional intelligence and alexithymic
      characteristics as the personality trait in cohorts of 267 college students and
      398 psychiatric outpatients. Score on the Toronto Alexithymia Scale were
      significantly correlated with those on the Emotional Intelligence Scale,
      suggesting that alexithymic characteristics are related to lower emotional
      intelligence. In conclusion, these data suggest that emotional intelligence
      overlaps with alexithymia.

PMID- 11824734
TI  - Leaders' bases of social power and anticipation of targets' resistance as
      predictors of transactional and transformational leadership.
AB  - This paper examines the value of power and resistance for predicting
      transactional and transformational leadership. A sample of 232 leader-follower
      dyads was used to examine these relationships using Hinkin and Schriesheim's 1989
      measure of power, Barbuto's 2000 measure of resistance, and Bass' 1985 measure of
      transformational leadership. Analysis yielded a significant negative relationship
      between leaders' Reward Power and their use of Individualized Consideration.

PMID- 11824735
TI  - Predicting the number of credit cards held by college students.
AB  - In a sample of 186 undergraduate students, the number of credit cards they held
      was associated with sex, their affective attitude toward credit cards, and an
      attitude of being careful with money.

PMID- 11824736
TI  - Attitudes towards the use of tests and test scores.
AB  - This exploratory study compared the perceived use of tests and test scores of 43
      adult education teachers and 130 teachers in the K-12 system tested earlier.

PMID- 11824737
TI  - Core conflictual relationship themes of men and women who are violent toward
      their partners.
AB  - The Core Conflictual Relationship Themes of men and women violent toward their
      partners and entering psychotherapy, students violent toward their partners, and
      nonviolent students (n = 84; n = 14 in each of the six groups) were compared. Men
      and women entering psychotherapy more often had negative Wish elements than
      others. The wish element was "to be loved" for 11 of the 14 student women violent
      toward their partners and 5 of the 14 nonviolent student women.

PMID- 11824738
TI  - Elderly suicide in China.
AB  - The rise in suicide rate among elderly people in China in recent years is
      noteworthy and may be associated with the increasing poverty of elderly people
      and the lack of social resources allocated to providing them with needed services
      to ensure their health and mental well-being.

PMID- 11824740
TI  - Inference of personality projected onto fictional characters having an author's
      first name.
AB  - Jane Austen projected some of her personality characteristics onto her fictional
      namesakes Jane Bennet in the novel Pride and Prejudice and Jane Fairfax in the
      novel Emma. Wishful fantasy seems satisfied by two attributes of both Janes. They
      are very beautiful, and they marry rich men they love. A feeling of inferiority
      was expressed by two attributes of both Janes, depicted as deficient in social
      communication and subordinate to the heroine of the novel.

PMID- 11824739
TI  - Breast cancer: education, counseling, and adjustment--a pilot study.
AB  - The feasibility of a randomized clinical trial to implement and compare the
      effectiveness of three components of an intervention for women with breast cancer
      and their partners was tested. The intervention components, standardized
      education by videotape (SE), telephone counseling (TC), and education with
      telephone counseling (SE+TC), were designed with a complementary approach to
      disease management of breast cancer at each of four phases of the breast cancer
      experience: diagnostic, postsurgery, adjuvant therapy, and ongoing recovery. A
      standardized Telephone Counseling Training Manual was developed. A nonprobability
      sample of 12 patient-partner pairs was accrued. Four pairs were randomly assigned
      to each of the three intervention components. A set of questionnaires was
      completed by each patient and partner at baseline and following each intervention
      for assessment of emotional, physical, and social adjustment, and perceived
      support. Attrition was minimal and return rate for the completed questionnaires
      at all five data-collection points was high. Validation of the SE and the TC, one
      of the objectives, was by data from the preliminary descriptive study (Hoskins,
      1990-1994), pretests and posttests for standardized education, audiotapes for
      each phase-specific telephone counseling session, and evaluation forms for each
      intervention session. The positive findings included significant changes from pre
      to postmeasurement in patients' and partners' scores for the standardized
      education in each of the four phases. Even with the limited statistical power,
      the effects were marked, lending support for a full-scale randomized clinical
      trial, to understand better the relative treatment efficacy and differential
      benefit of one or some interventions over others.

PMID- 11824741
TI  - Quality of life before and after lung transplantation in patients with emphysema
      versus other indications.
AB  - Whether lung transplantation improves Health-related Quality of Life in patients
      with emphysema and other end-stage lung diseases before and after lung
      transplantation was examined. Between 1992 and 1999, 23 patients with emphysema
      and 19 patients with other indications completed self-administered questionnaires
      before lung transplantation, and at 4, 7, 13, and 25 mo. after transplantation.
      The questionnaire included the Nottingham Health Profile, the State-Trait Anxiety
      Inventory, the Self-rating Depression Scale, the Index of Well-being, the self
      report Karnofsky Index, and four respiratory-specific questions. Neither before
      nor after transplantation were significant differences found on most dimensions
      of Health-related Quality of Life between patients with emphysema and other
      indications. Before transplantation, both groups report major restrictions on the
      dimensions Energy and Mobility of the Nottingham Health Profile, low experienced
      well-being, depressive symptoms, and high dyspnea. About 4 mo. after
      transplantation, most Health-related Quality of Life measures improved
      significantly in both groups. These improvements were maintained in the following
      21 mo.

PMID- 11824742
TI  - The Kuwait University Anxiety Scale: reliability and criterion-related validity
      in Syrian college students.
AB  - The Kuwait University Anxiety Scale was administered to 51 male and 56 female
      undergraduates in Syria. Respectively, the coefficients alpha for men, women, and
      the whole group were .91, .92, and .92; the test-retest rs after 14 to 21 days
      .88, .81, and .84; and the criterion-related validities .64, .62, and .64 against
      scores on Spielberger, et al.'s Trait Anxiety scale.

PMID- 11824743
TI  - Musical creativity and suicide.
AB  - The different abilities involved in artistic creativity may be mirrored by
      differences among mental disorders prevalent in each artistic profession, taking
      poets, painters, and composers as examples. Using suicide rates as a proxy for
      the prevalence of mental disorders in groups of artists, we investigated the
      percentage of deaths by suicide in a sample of 4,564 eminent artists who died in
      the 19th and 20th centuries. Of the sample, 2,259 were primarily involved in
      activities of a linguistic nature, e.g., poets and writers; 834 were primarily
      visual artists, such as painters and sculptors; and 1,471 were musicians
      (composers and instrumentalists). There were 63 suicides in the sample (1.3% of
      total deaths). Musicians as a group had lower suicide rates than literary and
      visual artists. Beyond socioeconomic reasons, which might favour interpretations
      based on effects of health selection, the lower rate of suicides among musicians
      may reflect some protective effect arising from music.

PMID- 11824744
TI  - Use of abnormal and health psychology as topics in a classroom format to reduce
      alcohol and other drug abuse among college students at risk.
AB  - This study was done to assess whether classes containing topics derived from two
      college courses, Abnormal Psychology and Health Psychology, could be used in a
      class room format to reduce alcohol and other drug abuse among at-risk college
      students. Topics covered included stress and stress management, alcohol and other
      drug use and abuse, chronic illnesses and psychological disorders that develop
      from an unhealthy lifestyle, and factors that play a role in good health and well
      being. Students were enrolled in a semester-long course for college credit as an
      alternative to punitive sanctions for on-campus alcohol violations and other drug
      violations. The Midwest Institute on Drug Use Survey and the CORE Alcohol and
      Drug Survey were administered on the first and last days of class. Analysis
      indicated a significant self-reported reduction in drug use and associated
      negative symptoms and behavioral effects. Women were more likely to report
      reductions in drug use than men.

PMID- 11824745
TI  - Anger vs guilt: inference of responsibility attribution and interpersonal
      reactions.
AB  - This study examined reactions toward an expression of anger or guilt.
      Participants' reactions were assessed after their partner for a collaborative
      task expressed anger or guilt due to failure on the task. Analysis indicated that
      participants inferred the attribution of responsibility made by the partner based
      on the expressed emotions; anger elicited an inference that the partner
      attributed the failure to the participant, while guilt led to an inference that
      the partner attributed the failure to the self. Further, expressers of anger were
      perceived as having more negative traits and were avoided more than those who
      expressed guilt. Discussion considered negative interpersonal effect of an
      expression of anger.

PMID- 11824746
TI  - Satisfaction with college by traditional and nontraditional college students.
AB  - University students (N=433) were surveyed about their satisfaction with a number
      of campus services and opportunities. Comparisons between traditional (up to 24
      years old) and nontraditional (25 years old and older) students indicated the
      latter valued learning and school opportunities more and appreciated the efforts
      of their professors in interacting with them and communicating information. A
      number of similarities were noted. University administrations need to be aware of
      the important differences between such groups to be able to enhance students'
      satisfaction.

PMID- 11824747
TI  - Distributions by age and sex of the dimensions of temperament and character
      inventory in a cross-cultural perspective among Sweden, Germany, and the USA.
AB  - Distribution by age and sex of the dimensions of the Temperament and Character
      Inventory were assessed cross-culturally for samples in Sweden, Germany, and the
      USA. The Temperament and Character Inventory is a 240-item (Sweden, 238-item),
      self-administered, true-false format, paper-and-pencil test developed by
      Cloninger and his coworkers based on his unified biosocial theory of personality.
      The inventory measures the Temperament dimensions Novelty Seeking, Harm
      Avoidance, Reward Dependence, and Persistence as well as the Character
      dimensions, Self-directedness, Cooperativeness, and Self-transcendence. The
      samples consisted of 300 German subjects, 300 Swedish subjects, and 300 U.S.
      subjects matched by age cohort and sex. Stability of the personality dimensions
      was evaluated across samples as were their age and sex distributions. We found
      significant effects of age, sex, and culture in univariate and multivariate
      comparisons on the personality dimensions. However, several significant
      differences in the personality dimensions for both European samples appear to be
      similar compared with those of the U.S. sample. We have to conclude that sex- and
      age-specific norms for the dimensions of the Temperament and Character Inventory
      are necessary given the established significant differences.

PMID- 11824748
TI  - Psychometric properties of the Life Regard Index-Revised: a validation study of a
      measure of personal meaning.
AB  - A validation study of the English version of the 28-item Life Regard Index
      Revised was undertaken with a sample of 91 participants from the general
      population. All previous studies of the Index have examined the Dutch version.
      The test-retest reliabilities at 8 wk. for the total Index (r =.87), Framework (r
      =.82), and Fulfillment (r =.81) subscales were very high. Cronbach alphas were
      .92, .83, and .87, respectively. A significant restriction of range was observed
      at the high-meaning end of the scale. Factor analysis only weakly supported the
      theorized two-factor structure. A very high disattenuated correlation between the
      Framework and Fulfillment subscales was observed (r=.94). The Index appeared to
      have adequate evidence supporting its concurrent and discriminant validity when
      compared with measures of hopelessness, spiritual well-being, and other measures
      of personal meaning. A significant positive association was found between the
      index and the Marlowe-Crowne Social Desirability Scale (r=.38). The Index was
      also significantly associated with sex (women scoring higher) and marital status
      (divorced people scoring lower). Revisions of the English version may address the
      restriction of range problem by employing a 5-point rating scale, instead of the
      current 3-point scale, or by adding more discriminating items. Further factor
      analytic studies with larger samples are needed before conclusions can be drawn
      regarding this scale's factor structure.

PMID- 11824749
TI  - College students with tattoos and piercings: motives, family experiences,
      personality factors, and perception by others.
AB  - The motives, family experiences, and personality characteristics of 341 college
      students with and without tattoos or piercings were studied. Participants
      completed Lippa's 1991 measures of the Big Five personality factors, a shortened
      version of the Body Cathexis Scale, a series of questions about their childhood
      experiences, and questions about risk-taking behaviors. In addition, reasons to
      have or not have body modifications and the perceptions of people with body
      modifications were investigated. Of the 116 men and 186 women, 25% and 33%,
      respectively, had at least one tattoo or body piercing. There were very few
      differences in the childhood experiences or personality characteristics of people
      with or without body modifications. Although people with body modifications did
      not differ from people without modifications on the Big Five personality
      measures, people without modifications perceived people with modifications as
      much different from themselves on these measures. These results indicate that
      tattoos and piercings in college students are associated with significantly more
      risk-taking behavior, greater use of alcohol and marijuana, and less social
      conformity. However, the traditional stereotype that body modifications are
      indicators of social or personal pathology does not describe contemporary college
      students.

PMID- 11824750
TI  - 1H-1H correlations across N-H...N hydrogen bonds in nucleic acids.
AB  - In 2HJ(NN)-COSY experiments, which correlate protons with donor/acceptor
      nitrogens across Nd...HNa bonds, the receptor nitrogen needs to be assigned in
      order to unambiguously identify the hydrogen bond. For many situations this is a
      non-trivial task which is further complicated by poor dispersion of (Na,Nd)
      resonances. To address these problems, we present pulse sequences to obtain
      direct, internucleotide correlations between protons in uniformly 13C/15N labeled
      nucleic acids containing Nd...HNa hydrogen bonds. Specifically, the pulse
      sequence H2(N1N3)H3 correlates H2(A,omega1):H3(U,omega2) protons across Watson
      CrickA-U and mismatched G.A base pairs, the sequences H5(N3N1)H1/H6(N3N1)H1
      correlate H5(C,omega1)/H6(C,omega1):H1(G,omega2) protons across Watson-Crick G-C
      base pairs, and the H2(N2N7)H8 sequence correlates
      NH2(G,A,C;omega1):H8(G,A;omega2) protons across G.G, A.A, sheared G.A and other
      mismatch pairs. These 1H-1H connectivities circumvent the need for independent
      assignment of the donor/acceptor nitrogen and related degeneracy issues
      associated with poorly dispersed nitrogen resonances. The methodology is
      demonstrated on uniformly 13C/15N labeled samples of (a) an RNA regulatory
      element involving the HIV-1 TAR RNA fragment, (b) a multi-stranded DNA
      architecture involving a G.(C-A) triad-containing G-quadruplex and (c) a peptide
      RNA complex involving an evolved peptide bound to the HIV-1 Rev response element
      (RRE) RNA fragment.

PMID- 11824751
TI  - Novel cross-strand three-purine stack of the highly conserved 5'-GA/AAG-5'
      internal loop at the 3'-end termini of Parvovirus genomes.
AB  - We have used two-dimensional nuclear magnetic resonance (2D-NMR), distance
      geometry (DG) and molecular dynamics / energy minimization (MD/EM) methods to
      study a 2 x 3 asymmetric internal loop structure of the highly conserved 5'
      (GA)/(AAG)-5' bubble' present at the 3'-end hairpin of the single-stranded DNA
      genome of parvoviruses. This motif contains an unpaired adenosine stacked between
      two bracketed sheared G.A pairs. However, the phenomenal cross-strand G-G and A-A
      stacking in the tandem sheared G.A pairs has undergone considerable change. A
      novel three-purine stacking pattern is observed instead; the inserted A18 base is
      completely un-stacked from its neighboring G 17 and A 19 bases, but well stacked
      with the cross-strand A4 and G3 bases to form a novel A4/A18/G3 stack that is
      different from the double G/G, A/A or quadruple G/G/G/G stack present in the 5'
      (GA)/(AG)-5' or 5'-(GGA)/(AGG)-5' motifs. Unlike the bulged purine residue that
      usually causes about 20 degree kink in the helical axis of the parent helix when
      bracketed by canonical G.C or A.T base pairs, no significant kink is observed in
      the present helix containing a bulged-adenine that is bracketed by sheared G.A
      pairs. The phosphodiesters connecting G3-A4 and G17-A18 residues adopt unusual
      zeta torsional angles close to the trans domain, yet that connecting A18-A19
      residues resumes the normal zeta(g-) value. The well structured '5'-(GAA)/(AG)-5"
      internal loop in the parvovirus genomes explains its resistance to single-strand
      specific endonuclease susceptibility.

PMID- 11824752
TI  - Automated prediction of 15N, 13Calpha, 13Cbeta and 13C' chemical shifts in
      proteins using a density functional database.
AB  - A database of peptide chemical shifts, computed at the density functional level,
      has been used to develop an algorithm for prediction of 15N and 13C shifts in
      proteins from their structure; the method is incorporated into a program called
      SHIFTS (version 4.0). The database was built from the calculated chemical shift
      patterns of 1335 peptides whose backbone torsion angles are limited to areas of
      the Ramachandran map around helical and sheet configurations. For each tripeptide
      in these regions of regular secondary structure (which constitute about 40% of
      residues in globular proteins) SHIFTS also consults the database for information
      about sidechain torsion angle effects for the residue of interest and for the
      preceding residue, and estimates hydrogen bonding effects through an empirical
      formula that is also based on density functional calculations on peptides. The
      program optionally searches for alternate side-chain torsion angles that could
      significantly improve agreement between calculated and observed shifts. The
      application of the program on 20 proteins shows good consistency with
      experimental data, with correlation coefficients of 0.92, 0.98, 0.99 and 0.90 and
      r.m.s. deviations of 1.94, 0.97, 1.05, and 1.08 ppm for 15N, 13Calpha, 13Cbeta
      and 13C', respectively. Reference shifts fit to protein data are in good
      agreement with 'random-coil' values derived from experimental measurements on
      peptides. This prediction algorithm should be helpful in NMR assignment, crystal
      and solution structure comparison, and structure refinement.

PMID- 11824753
TI  - Protein backbone structure determination using only residual dipolar couplings
      from one ordering medium.
AB  - Residual dipolar couplings provide significant structural information for
      proteins in the solution state, which makes them attractive for the rapid
      determination of protein folds. Unfortunately, dipolar couplings contain inherent
      structural ambiguities which make them difficult to use in the absence of
      additional information. In this paper, we describe an approach to the
      construction of protein backbone folds using experimental dipolar couplings based
      on a bounded tree search through a structural database. We filter out false
      positives via an overlap similarity measure that insists that protein fragments
      assigned to overlapping regions of the sequence must have self-consistent
      structures. This allows us to determine a backbone fold (including the correct
      Calpha-Cbeta bond orientations) using only residual dipolar coupling data
      obtained from one ordering medium. We demonstrate the applicability of the method
      using experimental data for ubiquitin.

PMID- 11824755
TI  - CPMG sequences with enhanced sensitivity to chemical exchange.
AB  - Improved relaxation-compensated Carr-Purcell-Meiboom-Gill pulse sequences are
      reported for studying chemical exchange of backbone 15N nuclei. In contrast to
      the original methods [J. P. Loria, M. Rance, and A. G. Palmer, J. Am. Chem. Soc.
      121, 2331-2332 (1999)], phenomenological relaxation rate constants obtained using
      the new sequences do not contain contributions from 1H-1H dipole-dipole
      interactions. Consequently, detection and quantification of chemical exchange
      processes are facilitated because the relaxation rate constant in the limit of
      fast pulsing can be obtained independently from conventional 15N spin relaxation
      measurements. The advantages of the experiments are demonstrated using basic
      pancreatic trypsin inhibitor.

PMID- 11824754
TI  - WaterLOGSY as a method for primary NMR screening: practical aspects and range of
      applicability.
AB  - WaterLOGSY represents a powerful method for primary NMR screening in the
      identification of compounds interacting with macromolecules, including proteins
      and DNA or RNA fragments. Several relay pathways are used constructively in the
      experiment for transferring bulk water magnetization to the ligand. The method is
      particularly useful for the identification of novel scaffolds of micromolar
      affinity that can be then optimized using directed screening, combinatorial
      chemistry, medicinal chemistry and structure-based drug design. The practical
      aspects and range of applicability of the WaterLOGSY experiment are analyzed in
      detail here. Competition binding and titration WaterLOGSY permit, after proper
      correction, the evaluation of the dissociation binding constant. The high
      sensitivity of the technique in combination with the easy deconvolution of the
      mixtures for the identification of the active components, significantly reduces
      the amount of material and time needed for the NMR screening process.

PMID- 11824756
TI  - Transverse relaxation optimized HCN experiment for nucleic acids: combining the
      advantages of TROSY and MQ spin evolution.
AB  - A three-dimensional MQ-TROSY-HCN pulse sequence is presented which provides intra
      base and sugar-to-base correlations for 13C, 15N labeled nucleic acids (RNA,
      DNA). The experiment simultaneously exploits the favorable relaxation properties
      of 1H-13C multiple quantum coherence for sugar carbons and of 13C TROSY-type spin
      evolution for base carbons. MQ-TROSY-HCN thus combines the advantages of MQ-HCN
      for sugar-to-base and TROSY-HCN for intra-base correlations in a single
      experiment. In addition, two slightly different implementations of the MQ-TROSY
      HCN experiment ensure optimal performance for small and larger oligonucleotides,
      respectively. The advantages of the MQ-TROSY-HCN experiment compared to the best
      previous implementations of HCN are demonstrated for a 33 nucleotide RNA aptamer.

PMID- 11824757
TI  - Improving the efficiency of the Gaussian conformational database potential for
      the refinement of protein and nucleic acid structures.

PMID- 11824758
TI  - A simple apparatus for generating stretched polyacrylamide gels, yielding uniform
      alignment of proteins and detergent micelles.
AB  - Compressed and stretched polyacrylamide hydrogels previously have been shown to
      offer a robust method for aligning proteins. A simple, funnel-like apparatus is
      described for generating uniformly stretched hydrogels. For prolate-shaped
      proteins, gels stretched in the direction of the magnetic field yield two-fold
      larger alignment than gels compressed to the same aspect ratio in this direction.
      Empirically, protein alignment is found to be proportional to (c-2.3)2 [(d(o/dN)3
      1], where do and dN are the diameters of the cylindrical gels before and after
      stretching, respectively, and c is the polyacrylamide weight fraction in percent.
      Low gel densities, in the 4-7% range, are found to have minimal effects on
      macromolecular rotational correlation times, tauc, and no effect of the
      compression ratio on tauc could be discerned over the range studied (do/dN < or =
      1.4). Application is demonstrated for a sample containing the first Ig-binding
      domain of protein G, and for a detergent-solubilized peptide.

PMID- 11824759
TI  - 1H, 13C and 15N chemical shift assignments of the N-terminal PAS domain of
      mNPAS2.

PMID- 11824760
TI  - 1H, 15N and 13C assignments of FLIN2, an intramolecular LMO2:ldb1 complex.

PMID- 11824761
TI  - Assignments of the 1H,13C, and 15N resonances of the substrate-binding SSD domain
      from Lon protease.

PMID- 11824762
TI  - Resonance assignments for cold-shock protein ribosome-binding factor A (RbfA)
      from Escherichia coli.

PMID- 11824763
TI  - Physostigmine, sodium bicarbonate, or hypertonic saline to treat diphenhydramine
      toxicity.
AB  - Diphenhydramine (DPH) is a commonly reported overdose that shares similar
      toxicities with other agents. such as tricyclic antidepressants, that interact
      with the fast sodium channels. Although physostigmine is considered an acceptable
      antidote for severe DPH toxicity, adverse effects such as seizures and
      cholinergic crisis may occur. We hypothesized that hypertonic saline or
      bicarbonate is equivalent or are better antidotes in an animal model of DPH
      toxicity. In a preliminary study. Sprague-Dawley rats were given toxic doses of
      DPH while continuous ECG, EEG, and blood pressure monitoring was performed.
      Seizures were the common toxic effect observed and was chosen. Four groups of 10
      rats each were established as control physostigmine, hypertonic sodium
      bicarbonate, and hypertonic saline(3%) treatment. Control had initial "drop-off"
      seizure burst rates over time; seizure bursts in the treatment groups were
      compared to these rates. Hypertonic sodium bicarbonate was the most effective
      treatment, followed closely by hypertonic saline. Hypertonic sodium bicarbonate
      may interact with DPH neuronal sodium channels and may be considered adjuvant
      therapy in humans with DPH-induced seizures.

PMID- 11824764
TI  - Suspected cresol poisoning in cattle presented for slaughter.
AB  - Cresol poisoning was suspected in agroup of cattle presented for slaughter at a
      federaly inspected plant in Illinois. Four cattle died shortly after being
      unloaded at the slaughter facility, while another animal died after being
      returned to the feedlot of origin in Iowa. The clinical signs in the affected
      cattle were lethargy, depression, ataxia, leg weakness, sternal recumbency,
      dehydration, and severe bloating. Metacresol (3-methyl phenol), commonly found in
      disinfectants used to clean and sanitize farm equipment and barns, was detected
      in rumen content from 4 necropsied animals ranging from 25.3 to 52.6 ppm. The
      exact source of exposure was not identified, but was probably accidental on the
      farm of origin or on the trailers used for animal transit to the slaughter plant.

PMID- 11824765
TI  - Zinc poisoning associated with separation anxiety in an Argentinean bulldog.
AB  - Separation anxiety in dogs is a complex behavioral syndrome produced by many
      causes. A hunter 4y-old male Argentinean Bulldog had dental disturbances and
      gastrointestinal and cutaneous symptoms due to high plasma zinc and low copper
      and calcium plasma concentration. His behavior made him bite galvanized wire
      fences in his cage and bunk that contained his food, both of a Zn-containing
      material. Specific treatment resulted in complete recovery.

PMID- 11824766
TI  - An unusual presentation of inhalant abuse with dissociative amnesia.
AB  - A 38-y-old male with occult inhalant abuse underwent an 18-mo evaluation for
      presumed seizure disorder. Although past medical history was significant for
      alcohol abuse, his wife confirmed a 6-y histoy of abstinence. His seizures were
      characterized as episodes of unconsciousness preceded by a feeling of "things
      slowing down". No muscular activity was witnessed during these episodes, and upon
      regaining consciousness the patient had slurred speech, disorientation,
      dissociative amnesia, and bizarre behavior that resolved spontaneously. Despite 4
      emergency department visits, 4 hospital admissions, 5 neurologic and 7
      psychiatric outpatient evaluations, extensive work-up was non-diagnostic. These
      episodes recurred until his wife found him huffing trichloroethylene. Questioning
      of the patient revealed that huffing always preceded these episodes and that he
      started huffing after discontinuing alcohol. The patient underwent addiction
      treatment. Toxic inhalants should be suspected as a substitute drug of abuse in
      patients attempting abstention. Disorientation clinically similar to dissociative
      amnesia can occur following loss of consciousness during an episode of
      trichloroethylene use.

PMID- 11824767
TI  - Hemolytic anemia after methylene blue therapy for aniline-induced
      methemoglobinemia.
AB  - Methylene blue is utilized as the main treatment of methemoglobinemia
      conventionally, but it may be ineffective in individuals with glucose-6-phosphate
      dehydrogenase (G6PD) deficiency. We report a G6PD-deficient patient who suffered
      from aniline-induced methemoglobinemia with initial good response Heinz body but
      hemolytic anemia appeared later 3 d after methylene blue therapy. G6PD deficiency
      was identified. He recovered uneventfully with hydration, packed blood
      transfusion and adjuvant luvela-N(dl-alpha-tocopheryl nicotinate) medication.
      Caution should be taken in using methylene blue as antidote of acute
      methemoglobinemia, especially when a history of G6PD deficiency is obscure.

PMID- 11824768
TI  - Accidental ingestion of alprazolam in 415 dogs.
AB  - Alprazolam is a benzodiazepine anti-anxiety agent that acts at the limbic,
      thalamic, and hypothalamic level of the CNS and has anxioytic. sedative,
      hypnotic, skeletal muscle relaxant, and anticonvulsant properties. A
      retrospective study was conducted of 415 alprazolam ingestions in dogs reported
      to the ASPCA Animal Poison Control Center between January 1998 and August 2000:
      238 suspected alprazolam toxicoses in dogs were evaluated. Clinical signs were
      ataxia/disorientation, depression, hyperactivity, vomiting, weakness, tremors,
      vocalization, tachycardia, tachypnea, hypothermia, diarrhea, and increased
      salivation that developed within 10-30 min post-ingestion. Treatment included
      standard decontamination procedures, such as emesis and activated charcoal: the
      specific benzodiazepine antagonist, flumazenil, may be used for severe CNS
      depression.

PMID- 11824769
TI  - Coma and apnea in a dog with hydroxyzine toxicosis.
AB  - Hydroxyzine is a commonly prescribed H1-receptor antagonist in small animal
      practice. The most common adverse effect reported after therapeutic dosing is
      mild sedation; severe reactions resulting in coma have occasionally been reported
      in children. We present a case of large po hydroxyzine exposure causing in coma
      and apnea in a dog. Exposure was confirmed with gas chromatography/mass
      spectrometry analysis of urine. Extensive therapeutic measures to enhance drug
      elimination and assist ventilation were required for 11 d. The positive outcome
      justifies critical care of similarly exposed animals. Veterinarians should be
      aware of the potential for coma and apnea secondary to hydroxyzine exposure.

PMID- 11824770
TI  - Lethality in a ram from the bite of a Palestine viper (Vipera xanthina
      palestinae).
AB  - A lethal bite to a 5-y-o ram from a Palestine viper is described. Severe
      edematous swelling in the pectoral area developed into skin, subcutaneous and
      muscle necrosis, accompanied by tachypnea, tachycardia, salivation and
      depression. Prominent biochemical findings were increased LDH, CK, urea and
      protein. The ram died because delayed treatment prevented successful antivenin
      administration.

PMID- 11824771
TI  - Multi-center retrospective evaluation of carbonyl iron ingestions.
AB  - There is limited published data concerning carbonyl iron ingestion and no data on
      overdose. A retrospective chart review of all patients with carbonyl iron
      ingestion reported to 5 regional poison information centers from January 1998 to
      April 2000 was done. Thirty-three patients with carbonyl iron ingestion were
      reported. Twenty-seven patients (82%) were managed without referral to a health
      care facility. The mean and median age of these patients was 3years and 20
      months, respectively. The mean dose ingested was 11.2 mg/kg (range of 2.2 to 34.5
      mg/kg) with no effects noted. Six patients evaluated in the emergency ingested a
      mean of 34 mg/kg (range of 12 to 72 mg/kg). The mean peak serum iron
      concentrations in 4/6 were 82 microg/dL (range of 36 to 177 microg/dL). One child
      with a history of flu-like symptoms reported diarrhea, fever and lethargy and had
      a serum iron concentration of 36 microg/dL; symptoms were believed unrelated to
      the exposure. In this limited first case series of iron carbonyl ingestion,
      serious toxicity did not occur.

PMID- 11824772
TI  - A lipid emulsion reduces mortality from clomipramine overdose in rats.
AB  - Tricyclic antidepressants are a common cause of self poisoning. Since these drugs
      are highly lipid soluble, we examined the interaction between imipramine and a
      lipid emulsion. Rats were given an iv dose of imipramine with either normal
      saline or a lipid emulsion as vehicle. The rats who received the lipid emulsion
      had a significantly lower mortality. The role of lipid emulsions poisoning
      therapy is reviewed.

PMID- 11824773
TI  - Analysis of 156 cases of plant intoxication received in the Toxicologic
      Information Center at Catholic University of Chile.
AB  - We present a retrospective analysis of plant and mushroom ingestions reported to
      the Toxicologic Information Center at the Catholic University of Chile. All the
      phone calls of plant and mushroom intoxications received from January 1998
      through June 2000, were classified according to agent, clinical presentation,
      affected age group, origin of the phone call, and time from exposure to the toxic
      agent. Of 36,580 consultations received, 156 were intoxications with plants or
      mushrooms, and 53.9% of them affected children < 6years. Most patients were
      symptomatic at consultation, with digestive, neurologic, anticholinergic or
      cutaneous effects. The most frequent accidental ingestions were of elephant's ear
      (Colocasia sp) by children, causing digestive symptoms, and by intentional
      ingestions of black henbane (Hyoscyamus niger) by adolescents, causing
      anticholinergic symptoms; 5 cases of Amanitaphalloides wer ereported with 3 fatal
      due to fulminant hepatic damage. Plant and mushroom intoxications are an uncommon
      event, but can seriously compromise those that ingest them. Despite its low
      incidence, public and medical community education is essential to prevent and
      manage these intoxications efficiently.

PMID- 11824774
TI  - Accidental Datura stramonium poisoning in a dog.
AB  - Datura stramonium is potentially poisonous to humans and livestock; however,
      there's little description of clinical and pathological findings in dogs
      naturally intoxicated. We report an accidental Datura stramonium poisoning in a
      dog emphasizing the importance of recognizing the classical signs of
      anticholinergic poisoning.

PMID- 11824775
TI  - Clinical effects of brimonidine ophthalmic drops ingestion in 52 dogs.
AB  - Brimonidine is an ophthalmic solution of 0.2% brimonidine tartrate used to lower
      intraocular pressure in human glaucoma patients. A retrospective study was
      conducted of brimonidine ophthalmic solution ingestion in 52 dogs reported to the
      ASPCA Animal Poison Control Center between January 1998 and December 2000. Eighty
      percent of the dogs were < 1-y of age. Approximate ingested dosages ranged from
      0.18-5.55 mg/kg. Incidence of clinical signs were bradycardia (67%), depression
      (46%), ataxia (27%), hypotension (25%), pallor (23%), weakness (17%), change in
      mucous membrane color (17%), hypothermia (13%), vomiting or retching (13%.).
      Shock, weak pulses, and poor capillary refill time were also reported. Treatment
      involved early decontamination, supportive care, andyohimbine and atipamezole as
      specific alpha-2 antagonists that could be helpful in reversing the effects of
      brimonidine. Due to the possibility of severe cardiovascular effects developing,
      the ingestion of brimonidine ophthalmic solution in dogs should be considered
      dangerous.

PMID- 11824776
TI  - An approach to dialysis for ethylene glycol intoxication.
AB  - Eleven cases of ethylene glycol ingestion were retrospectively analyzed for
      presentation, treatment, and outcome. Patients were grouped according to the time
      it took to receive medical attention, and whether or not they received I
      continuous hemodialysis (CHD) versus intermittent hemodialysis (IHD). Six
      patients presented within 12 h of exposure (Group 1), whereas 5 patients
      presented later (Group 2; range 48-120 h). Comparisons were made for age,
      ethylene glycol level, anion gap, osmolar gap, pH, admission creatinine level,
      time from ingestion to presentation, total time spent on hemodialysis, number of
      dialysis treatments, recovery time, recovery creatinine, hospital length of stay,
      and status. Significant differences were observed for ethylene glycol level,
      osmolar gap, and presentation time. Ten of the 11 patients received single pass
      hemodialysis, and 5 of these received I CHD. Of the 5 patients who received CHD
      versus the 5 patients who received IHD, none developed complications (p=0.004).
      Patients who presented within 10 h of exposure had fewer complications than those
      who presented > 12 h after exposure Timely CHD is superior to IHD in treating
      ethylene glycol intoxication. An adeQuate time course of hemodialysis can be
      approximated using the ethylene gycol index, and may eliminate reliance on
      ethylene glycol levels in determining adequate endpoints of dialysis in treating
      poisoned patients.

PMID- 11824777
TI  - Prolonged survival after experimental paraquat intoxication: role of alternative
      antioxidants.
AB  - Since paraquat poisoning causes multiorgan damage through the generation of
      several redox products, the usual therapy includes antioxidative drugs, such as N
      acetylcysteine. We investigated whether selected antioxidative drugs can improve
      survival from acute paraquat toxicity. Forty-eight male 2-3-mo-old Wistar rats
      were divided into 4 groups receiving paraquat dichloride in a single injection
      (11 mg/kg bw ip) I h before the administration of normal saline (control ip), S
      carboxymethylcysteine (600 mg/kg bw po), propofol (100 mg/kg bw ip) or
      trimetazidine (10 mg/kg bw po). Animals were observed for 7 d. The median
      survival time in the control group was 3 d whereas it was 4 (p = 0.15), 4.5 (p <
      0.05) or 5 (p < 0.05) d for the trimetazidine, S-carboxymethylcysteine or
      propofol-treated groups, respectively.

PMID- 11824778
TI  - The uncertainty of the toxic effect of stings from the Urtica nettle on hunting
      dogs.
AB  - This paper questions the effect of the sting from the Urtica species of nettle on
      hunting dogs, particularly in the US. Research in this area is limited and is
      reflected in the wide use of a particularly unsound literature reference on the
      subject. A general account is given of which types of "nettle" plant have a toxic
      sting, how the mechanism of the sting works, and the toxic substances it
      contains. The effects experienced by hunting dogs appear to represent a condition
      other than contact urticaria, which is normall the result of being stung by
      nettles (Urticas in particular). The possibility is discussed that the signs were
      caused by another plant, also commonly labelled a nettle, or that possibly they
      were caused by other than the direct stinging of soft tissues. Further research
      should be done on the toxic elements in the sting of Urtica chamaedryoides,
      indicated in some literature as the "guilty" plant.

PMID- 11824779
TI  - Development of a standardized animal model for the study of alkali ingestion.
AB  - The purpose of this study was to develop an animal model that would grade in-vivo
      therapeutic modality testing for caustic ingestion. Caustic substances are found
      in many household items (eg detergents, bleaches, pipe cleaners) and pose a
      serious threat to health if ingested accidentally or intentionally with resulting
      injuries including immediate death or chronic debilitating morbidity. This study
      used 5, 3.8 or 1.8% sodium hydroxide (NaOH) to determine macro/microscopic injury
      at 10, 30, or 60 minutes. Macroscopic grading was based on gross evaluation of
      denudation of mucosa, edema, hyperemia, hemorrhage, ulcerations and necrosis.
      Microscopic grading was based on epithelial viability, cornified epithelial cell
      differentiation, granular cell differentiation, epithelial cell nuclei, muscle
      cell viability and muscle cell nuclei. Product concentration was shown a more
      significant predictor of injury than time of exposure. The grading system
      presented should provide a reliable method of producing and grading alkaline
      ingestions for future treatment hypothesis testing.

PMID- 11824780
TI  - Metformin associated acute pancreatitis.
AB  - Metformin poisoning is not common and is usually associated with lactic acidosis
      and acute hepatitis. A case of metformin-poisoning associated with acute
      pancreatitis is reported here for the first time.

PMID- 11824781
TI  - Pesticide-related illness: are poison centers reporting to the state health
      department?
AB  - Pesticide-related illness should be reported by physicians to state health
      departments. Since poison centers (PC) are involved in the management of many of
      these cases, it may be assumed that they should report these cases. A 5-y audit
      of pesticide related illness reported to a centralized state pesticide oversight
      agency (PARC) was conducted. During the 5-y period the PC received 5,828 calls
      involving exposures to reportable pesticides; 1,011 of these were for
      organophosphates. Eight organophosphates cases were treated with antidotes, but
      ony 2 were reported as a pesticide-related illness. During this same time PARC
      reviewed 540 cases of persons suspected of being exposed to pesticides. The
      largest percent of referrals (19.6%) came from the PC, however only 1% of all PC
      pesticide exposure cases were reported as pesticide-related illnesses.

PMID- 11824783
TI  - Retrieving "old"- and "new"-information!

PMID- 11824782
TI  - Efficacy of hexafluorine for emergent decontamination of hydrofluoric acid eye
      and skin splashes.

PMID- 11824784
TI  - Diterpenoid alkaloid toxicosis in cattle in the Swiss Alps.
AB  - Between 1995 and 1999, several cattle of a group of 80 heifers died acutely on a
      pasture in the Swiss Alps. The animals were Found dead between July 9th and 15th
      eachyear. Only 1 animal was examined on post-mortem, and no significant lesions
      were found. Aconitum vulpera, A napellus, and Delphinium elatum were identified
      in the pasture. The presence of diterpenoid alkaloid-containing plants in the
      pasture, the rapid death of the animals, and the lack of pathologic lesions
      suggested diterpenoid alkaloid toxicosis as a cause of death. A multiresidue
      alkaloid screen using gas chromatography with a mass spectrometric detector was
      employed on rumen, abomasal, small intestine, and cecal contents from the I
      heifer. Deltaline, deltamine, and lycoctonine were identified. Aconitine was
      found in all gastrointestinal samples using a sensitive and highly specific
      liquid chromatography/mass spectrometry methodology for aconitine analysis. The
      findings ofditerpenoid alkaloids in the gastrointestinal contents confirmed
      exposure to Delphinium and Aconitum spp, possibly resulting in sudden death.

PMID- 11824785
TI  - Cytosolic import factor- and Ran-independent nuclear transport of ribosomal
      protein L5.
AB  - Ribosomal protein L5 is a shuttling protein that, in Xenopus oocytes, is involved
      in the nucleocytoplasmic transport of 5S rRNA. As demonstrated earlier, L5
      contains three independent nuclear import signals (NLSs), which function in
      oocytes as well as in somatic cells. Upon physical separation, these NLSs differ
      in respect to their capacity to bind to nuclear import factors in vitro and to
      mediate the nuclear import of a heterologous RNP in vivo. As reported in this
      communication, analysis of the in vitro nuclear import activity of these three
      NLSs reveals that they also differ in respect to their requirements for cytosolic
      import factors and Ran. Nuclear import mediated by the N-terminal and the central
      NLS depends on cytosolic import factor(s) and Ran, whereas import via the C
      terminal NLS occurs independently from these factors. Thus, the presence of
      multiple NLSs in ribosomal protein L5 appears to allow for efficient nuclear
      transport via utilisation of multiple, mechanistically different import pathways.

PMID- 11824786
TI  - Core histones and linker histones are imported into the nucleus by different
      pathways.
AB  - Histones are the major structural proteins in eukaryotic chromosomes. This group
      of small very basic proteins consists of the H1 linker histones and the core
      histones H2A, H2B, H3 and H4. Despite their small size, the nuclear import of
      histones occurs by an active transport mechanism and not simply by diffusion.
      Histones contain several nuclear localisation signals (NLS) that can be
      subdivided into two different types of signal structures. We have previously
      shown that H1 histones are transported by a heterodimeric import receptor complex
      consisting of importin beta and importin 7, and we now describe the receptors
      required for the import of the core histones. Competition experiments using the
      in vitro transport assay indicate that the import pathway of the core histones
      differs from that of the linker histones and of nuclear proteins with classical
      NLS. In vitro binding assays show that each of the import receptors importin
      beta, importin 5, importin 7 and transportin, has the capacity to bind to any of
      the four core histones. Reconstitution experiments with recombinant factors
      indicate that each of these factors can independently serve as an import receptor
      for each of the core histones.

PMID- 11824787
TI  - Microtubule-dependent assembly of the nuclear envelope in Xenopus laevis egg
      extract.
AB  - Microtubules take part in several mechanisms of intracellular motility, including
      organelle transport and mitosis. We have studied the ability of Xenopus egg
      extract to support nuclear membrane and pore complex formation when microtubule
      dynamics are manipulated. In this report we show that the formation of a nuclear
      envelope surrounding sperm chromatin requires polymerized microtubules. We have
      observed that microtubule-depolymerizing reagents, and AS-2, a known inhibitor of
      the microtubule motor protein kinesin, do not inhibit the formation of a double
      nuclear membrane. However these double membranes contain no morphologically
      identifiable nuclear pore complexes and do not support the accumulation of
      karyophilic proteins. In contrast, the assembly of annulate lamellae, cytoplasmic
      structures containing a subset of pore complex proteins, was not affected. Our
      data show that not only polymerized microtubules, but also the microtubule motor
      protein kinesin, are involved in the formation of the nuclear envelope. These
      results support the conclusion that multiple nuclear envelope-forming mitotic
      vesicle populations exist, that microtubules play an essential and selective role
      in the transport of nuclear envelope-forming vesicle population(s), and that
      separate mechanisms are involved in nuclear envelope and annulate lamellae
      formation.

PMID- 11824788
TI  - Vimentin and desmin of a cartilaginous fish, the shark Scyliorhinus stellaris:
      sequence, expression patterns and in vitro assembly.
AB  - In the shark Scyliorhinus stellaris we have biochemically identified and cDNA
      cloned orthologs of human vimentin and desmin, SstV and SstD, as deduced from
      immunoblotting and sequence alignment with teleost, frog and human vimentin and
      desmin, respectively. This allowed us to further clarify the relationship of
      previously identified lower vertebrate intermediate filament proteins to
      mammalian vimentin and desmin. Immunofluorescence microscopy with antibodies H5
      and VIM13.2 showed vimentin expression in shark eye and brain and absence in
      epithelia, which resembles the situation in higher vertebrates. In addition, SstV
      is expressed in many mesenchymal cell types which corresponds to the case in
      terrestrial vertebrates but strongly differs from teleosts. Surprisingly, shark
      interstitial cells, including fibroblasts, express neither SstV nor keratins but
      other as yet unidentified intermediate filament proteins as deduced from their
      reactivity with antibody IFA. In vitro assembly studies of recombinant SstV
      revealed a temperature optimum for uncompromised filament assembly of 15 degrees
      C. At 18 degrees C, but more pronounced at 21 degrees C and 24 degrees C, which
      is notably above the animal's inherent preferred environmental temperature, both,
      SstV and SstD assemble into thick and inflexible fibers. Thus, environmental
      temperature apparently is, as a general principle, a driving force for the fine
      tuning of protein primary structure and eventually 3D structure.

PMID- 11824789
TI  - Plant Golgi-associated vesicles contain a novel alpha-actinin-like protein.
AB  - By using Western blotting, immunofluorescence and immunogold labeling, a novel
      alpha-actinin-like protein was found in pollen and pollen tubes of Lilium
      davidii, a model system for cytoskeleton and Golgi apparatus study of plant. As
      measured by Western blotting, the molecular mass of the a-actinin-like protein
      was about 80 kDa. Under confocal laser scanning microscopy after
      immunofluorescence labeling, the distribution of the alpha-actinin-like protein
      appeared punctated in the cytoplasm of the pollen and pollen tubes. When double
      labeled, the protein was co-localized with Golgi 58K protein. In addition, some
      fraction of the alpha-actinin-like protein was found to co-distribute with F
      actin bundles in the pollen tubes. Additional studies with immuno-gold labeling
      and transmission electron microscopy revealed that the alpha-actinin-like protein
      bound mainly to the membranes of Golgi-associated vesicles. When the pollen tubes
      were treated with Brefeldin A (BFA), the a-actinin-like proteins were dispersed
      into the cytoplasm, and the growth of pollen tubes was inhibited. After BFA was
      removed, the protein was reversibly recovered on the Golgi apparatus. These
      results suggest that the novel alpha-actinin-like protein is a BFA-sensitive
      protein on the membranes of Golgi-associated vesicles, and may participate in
      Golgi-associated vesicles budding and/or sorting, together with actin
      microfilaments.

PMID- 11824790
TI  - Expression and immunolocalization of the aquaporin-8 water channel in rat
      gastrointestinal tract.
AB  - A remarkable amount, of water is transported in the gastrointestinal (GI) organs
      to fulfil the secretory and absorptive functions of the GI tract. However, the
      molecular basis of water movement in the GI epithelial barriers is still poorly
      known. Important clues about the mechanisms by which water is transported in the
      GI tract were provided by the recent identification of multiple aquaporin water
      channels expressed in GI tissues. Here we define the mRNA and protein expression
      and the cellular and subcellular distribution of aquaporin-8 (AQP8) in the rat GI
      tract. By semi-quantitative RT-PCR the AQP8 mRNA was detected in duodenum,
      proximal jejunum, proximal colon, rectum, pancreas and liver and, to a lesser
      extent, in stomach and distal colon. Immunohistochemistry using affinity-purified
      antibodies revealed AQP8 staining in the absorptive epithelial cells of duodenum,
      proximal jejunum, proximal colon and rectum where labeling was largely
      intracellular and confined to the subapical cytoplasm. Confirming previous
      results, AQP8 staining was seen at the apical pole of pancreatic acinar cells.
      Interestingly, both light and immunoelectron microscopy analyses showed AQP8
      reactivity in liver where labeling was associated to hepatocyte intracellular
      vesicles and over the plasma membrane delimiting the bile canaliculi. A complex
      pattern was observed by immunoblotting with total membranes of the above GI
      organs incubated with affinity-purified anti-AQP8 antibodies which revealed
      multiple bands with molecular masses ranging between 28 and 45 kDa. This
      immunoblotting pattern was not modified after deglycosylation with N-glycosidase
      F except the 34-kDa band of liver that, as already reported, was partially down
      shifted to 28 kDa. No bands were detected after preadsorption of the anti-AQP8
      antibodies with the immunizing peptide. The cellular and subcellular distribution
      of AQP8 suggest physiological roles for this aquaporin in the absorption of water
      in the intestine and the secretion of bile and pancreatic juice in liver and
      pancreas, respectively. The large intracellular expression of AQP8 may indicate
      its recycling between the cytoplasmic compartment and the plasma membrane. The
      cytoplasmic localization observed may also relate to the involvement of AQP8 in
      processes of intracellular osmoregulation.

PMID- 11824791
TI  - Expression of the stress-induced p8 mRNA is transiently activated after culture
      medium change.
AB  - We report here that the mere fact of changing culture medium for fresh medium
      induced in several cell lines the expression of stress-activated genes including
      protein kinases p38, JNK and ERK1/2 and the transcription factor C/EBPbeta. As a
      consequence, p8, a gene induced by stress in several tissues, was strongly up
      regulated. Induction did not occur after change for cell-conditioned medium.
      Induction was however transient, with a peak at 60 min for p38, at 15-30 min for
      JNK and at 15 min for ERK1/2, at 2-3 hours for C/EBPbeta and at 4-6 hours for p8.
      Repression of the induction was due to the secretion of thermolabile molecule(s)
      that progressively conditioned the medium. As low as 25% of conditioned medium
      added to fresh culture medium was sufficient to abolish the stress response.
      Taken together, our data indicate that the renewal of culture medium induces a
      transient cellular stress that may be a source of artifacts in experiments
      performed shortly after a change of culture medium.

PMID- 11824792
TI  - Histone deacetylase inhibitors induce apoptosis in peripheral blood lymphocytes
      along with histone H4 acetylation and the expression of the linker histone
      variant, H1 degrees.
AB  - The results of this study show that H1 degrees can be induced by sodium butyrate
      and trichostatin A in peripheral blood lymphocytes, a cell system which does not
      normally express this linker histone variant. Moreover, this induced expression
      was found to be correlated in a dose-dependent manner with the concomitant
      induction of apoptosis and increased levels of histone H4 acetylation. Sodium
      butyrate and trichostatin A, both inhibitors of histone deacetylases, are known
      to induce terminal differentiation and at the same time the induction of the
      linker histone variant, H1 degrees, in a number of tissue/cell systems. Moreover,
      aside from induced expression by histone deacetylase inhibitors, H1 degrees gene
      expression has also been tightly associated with the process of terminal
      differentiation in many physiological tissue/cell systems. The concomitant
      induction of H1 degrees expression along with apoptosis and histone acetylation
      in the same cell system has not been previously reported. Histone acetylation is
      known to be involved in chromatin remodelling events. Such events also occur
      during apoptosis. The association of H1 degrees gene expression with apoptosis,
      and not with differentiation in these cells, leads to more general implications
      as to a potential functional role of H1 degrees during chromatin remodelling.

PMID- 11824793
TI  - Genetic risk factors in chronic pancreatitis.

PMID- 11824794
TI  - Effects of interleukin-8 and Helicobacter pylori on histamine release from
      isolated canine gastric mucosal mast cells.
AB  - BACKGROUND: In recent studies, the involvement of mast cells in the pathogenesis
      of Helicobacter pylori infection was suggested. In the present study, using
      isolated canine gastric mucosal mast cells, we undertook to elucidate the effects
      of interleukin-8 (IL-8) and H. pylori on histamine release from these cells.
      METHODS: Enriched canine gastric mucosal mast cells (50% target cells) were
      incubated in Hanks medium with IL-8, or water extract or sonicate of H. pylori
      for 15 min at 37 degrees C. The content of histamine in the supernatants and the
      cell pellets after centrifugation was assayed with a histamine radioimmunoassay
      (RIA) kit. RESULTS: IL-8 (50 ng/ml) and concanavalin A (20 microg/ml)
      significantly increased histamine release from enriched gastric mucosal mast
      cells. Dose-dependent stimulation of histamine release by IL-8 (5-50 ng/ml) was
      also seen. Water extract and sonicate of H. pylori (10(8) bacteria) increased
      histamine release from mast cells. A concentration-dependent stimulation of
      histamine release by water extract or sonicate was also seen. The maximal
      response of histamine release was seen at the highest concentration of the water
      extract or sonicate. CONCLUSIONS: The results indicated that IL-8 and H. pylori
      had stimulatory effects on histamine release from canine gastric mucosal mast
      cells. The results imply that IL-8 and soluble factors of H. pylori may
      accelerate inflammation of the gastric mucosa via histamine release from mast
      cells.

PMID- 11824795
TI  - Regression of low-grade gastric mucosa-associated lymphoid tissue lymphoma after
      eradication of Helicobacter pylori: possible association with p16
      hypermethylation.
AB  - BACKGROUND: Many reports have stated that the cure of Helicobacter pylori
      infection can induce a complete remission of low-grade gastric mucosa-associated
      lymphoid tissue (MALT) lymphoma. Although p16 hypermethylation was frequently
      found in MALT lymphoma, the association between this finding and the remission of
      MALT lymphoma has not been clarified. We performed a prospective study to
      evaluate the outcome of patients with low-grade gastric MALT lymphoma and the
      expression of p16 hypermethylation. METHODS: We prospectively enrolled 20
      patients with H. pylori-positive low-grade gastric MALT lymphoma (stage I E1).
      After the eradication of H. pylori, the patients were regularly followed-up with
      endoscopic and histological assessment. The methylation-specific polymerase chain
      reaction (PCR) (MSP) method was used for the serial detection of p16
      hypermethylation. RESULTS: Eighteen patients (90%) achieved complete remission,
      with a median duration of 15.7 months. The initial detection rate of p16
      hypermethylation was 58% (7 of the 12 patients in whom p16 hypermethylation was
      evaluated successfully). In a serial investigation, 3 patients who were followed
      up for a median 28 months showed that the p16 hypermethylation had disappeared.
      CONCLUSIONS: Complete remission of low-grade gastric MALT lymphoma after the
      eradication of H. pylori infection can be maintained for more than 1 year.
      Further studies are warranted to investigate the role of p16 hypermethylation in
      the pathogenesis of gastric MALT lymphoma.

PMID- 11824796
TI  - CT and 99mTc-WBC vs colonoscopy in the evaluation of inflammation and
      complications of inflammatory bowel diseases.
AB  - BACKGROUND: The goal of this study was to evaluate the accuracy of computerized
      tomography (CT) and 99mTc-white blood cell (WBC) scintigraphy versus colonoscopy
      in assessing inflammatory bowel diseases (IBD) in a large population of children.
      METHODS: In a patient population of 313 consecutive children who had a 99mTc-WBC
      scan, 106 colonoscopies were done within a median time interval of 8 days of the
      99mTc-WBC scan. One hundred and three CT scans were performed on 84 patients.
      RESULTS: Of the 42 CT scans obtained within a short time interval after the 99mTc
      WBC scan, 21 (50%) were normal. In the 21 children with a positive 99mTc-WBC
      scan, 62% (13/21) of the CT scans underestimated the bowel wall inflammation in
      at least one segment. In the children with a negative 99mTc-WBC study, there were
      17 negative CT examinations and 4 examinations showing an abnormal terminal
      ileum. When CT was compared with colonoscopy in assessing inflammation, there
      were five true-negative CT, two true-positive CT, no false-positive, and seven
      false-negative CT examinations. When 99mTc-WBC scintigraphy was compared with
      colonoscopy in assessing inflammation, there were seven true-positive, two false
      negative, five true-negative, and no false-positive 99mTc-WBC studies. The 99mTc
      WBC scan was positive in five patients with a false-negative CT examination. Of
      the total 103 CT scans obtained, 53 (51%) were normal. Four abscesses (3.8%) were
      demonstrated by CT. CONCLUSIONS: 99mTc-WBC scintigraphy is more sensitive than CT
      for detecting inflammation of the bowel wall. The incidence of complications from
      IBD in this retrospective study was much lower than had been previously reported.

PMID- 11824797
TI  - Evaluation of the clinical course of acute attacks in patients with ulcerative
      colitis through the use of an activity index.
AB  - BACKGROUND: Because it is not easy to make a clinical decision regarding surgical
      treatment in patients with acute attacks of ulcerative colitis, an objective,
      simple, criterion is needed to determine the optimum timing for colectomy. The
      aim of this study was to retrospectively examine to what extent an activity index
      (AI) can evaluate the clinical course in such acute attacks. METHODS: One hundred
      and twenty-seven patients with moderate or severe attacks of ulcerative colitis
      were examined. AI values and the decline in AI values were compared between
      surgical and nonsurgical groups after 1 week and 2 weeks of medical therapy. To
      evaluate the clinical course of acute attacks, cutoff AI values were set at every
      10 points between values of 180 and 210. The positive predictive value for
      surgery was examined. RESULTS: AI values in the surgical group were significantly
      higher than those in nonsurgical group at pretreatment, and after 1 or 2 weeks of
      medical therapy. The decline of AI values in the nonsurgical group was
      significantly higher than that in the surgical group after 1 or 2 weeks of
      medical therapy. At pretreatment, the prediction of colectomy was less than 50%
      at any of the cutoff values. After 1 week of therapy, approximately 60% of
      patients with an AI value greater than any of the cutoff AI values required
      colectomy. After 2 weeks of therapy, 30 of 43 (70%), 28 of 38 (74%), 24 of 29
      (83%), and 17 of 21 (81%) patients with AI values greater than 180, 190, 200, and
      210, respectively, required colectomy. Overall accuracy was 86%, 87%, 88%, and
      83% for cutoff AI values of 180, 190, 200, and 210, respectively. Because the
      overall accuracy and positive predictive value for colectomy at AI values of 200
      were significantly higher than these parameters at other AI values after 2 weeks
      of therapy, an AI value of 200 was regarded as the cutoff value most able to
      predict colectomy. CONCLUSIONS: We concluded that patients with an AI value in
      excess of 200 after 2 weeks of medical therapy would require surgical treatment.

PMID- 11824798
TI  - Clinical characteristics of patients infected with hepatitis B virus genotypes A,
      B, and C.
AB  - BACKGROUND: The aim of the present study was to evaluate the clinical
      characteristics at first hospital consultation, according to the genotype of
      hepatitis B virus (HBV), in patients with chronic liver diseases and positivity
      for hepatitis B surface antigen (HBsAg) in metropolitan Tokyo. METHODS: The
      subjects consisted of 1077 patients with chronic liver diseases who were HBsAg
      positive. HBV genotype was determined by an enzyme-linked immunosorbent assay
      (ELISA), using PreS2 monoclonal antibody, which is specific for HBV genotypes in
      the PreS2 region. RESULTS: The proportion of patients with genotype A was 2% (20
      patients), genotype, B 9% (101 patients), and genotype C, 88% (945 patients),
      while 11 patients (1.0%) had other genotypes, including 2 (0.2%) each with
      genotypes D and F, and 7 (0.6%) that were untypeable. Patients with genotype A
      were significantly (P = 0.049) more likely to be positive for Hepatitis B
      envelope antigen (HBeAg) at the first consultation compared with those with
      genotype B. Patients with genotype B were significantly more likely to be HBeAg
      negative at the first consultation compared with those with genotype A (P =
      0.049) and genotype C (P = 0.001), significantly more likely to show minimal
      hepatic fibrosis (P = 0.003), and least likely to develop liver cirrhosis (P =
      0.005). Patients with genotype C were likely to be HBeAg-positive (P = 0.001) and
      to have a positive family history of HBV infection (P = 0.0002). CONCLUSIONS: The
      clinical features of patients with HBV infection in metropolitan Tokyo varied
      depending on the HBV genotype.

PMID- 11824799
TI  - Possible mechanisms of elevation of serum transaminase levels during interferon
      beta therapy in chronic hepatitis C patients.
AB  - BACKGROUND: Serum transaminase levels are frequently elevated in patients with
      chronic hepatitis C who are receiving interferon (IFN)-beta therapy, despite
      hepatitis C virus (HCV)-RNA being eradicated from the serum. We examined liver
      histology to determine the reason for this elevation. METHODS: Patients with
      chronic hepatitis C, diagnosed by liver histology and positive serum HCV-RNA,
      were given intravenous injections of IFN-beta, at a daily dose of 6 MU, every day
      for periods of 6 to 12 weeks. When serum alanine transaminase (ALT) levels during
      the therapy were higher than three times the levels before the therapy, liver
      biopsy was performed. Histological findings on light microscopy were compared in
      liver biopsy specimens obtained before and during the therapy. RESULTS: An
      increase in serum ALT levels was found in 19 of the 102 patients who received the
      IFN-beta therapy. Autoimmune hepatitis was not contributory in any of these 19
      patients, because serum antinuclear antigen was negative and IgG levels were not
      increased. Liver histology was examined in 10 of these 19 patients. The period
      between the start of IFN-beta therapy and the biopsy during the therapy ranged
      from 14 to 46 days. In 2 patients, the extent of mononuclear cell infiltration in
      the liver and hepatocyte necrosis was less than the extent before the therapy. In
      the remaining 8 patients, the grade of chronic hepatitis was unchanged during,the
      therapy, but vacuole formation and apoptotic nuclei in hepatocytes were found in
      2 patients, and centrilobular necrotic areas in 1 patient. CONCLUSIONS: The
      elevation of serum ALT levels during IFN-beta therapy in chronic hepatitis C
      patients was not a result of increased hepatitis activity. Degenerative,
      apoptotic, and necrotic changes in hepatocytes, probably a result of the
      cytotoxic effects of IFN-beta, may have contributed to this elevation of ALT
      levels. However, such changes were absent in most of the patients, suggesting
      that decisions on the discontinuation of IFN-beta therapy must be made in
      accordance with liver histology findings.

PMID- 11824800
TI  - Crohn's disease associated with gastric cancer.
AB  - An association between Crohn's disease and gastric cancer has not been clearly
      defined. A 34-year-old man was referred to our hospital for the evaluation of a
      gastric lesion and treatment of small-bowel Crohn's disease. We diagnosed the
      gastric lesion as adenocarcinoma, using endoscopy and histological studies. The
      patient underwent a distal gastrectomy, with well-differentiated adenocarcinoma
      being found; partial resection of the small bowel was also performed because of
      an entero-enteric fistula. His postoperative course was uncomplicated.

PMID- 11824801
TI  - Reactivation of sarcoidosis during interferon therapy.
AB  - The exacerbation of a co-existing autoimmune disease is often a concern for
      physicians who use immunomodulating agents for the treatment of a concomitant
      process. As physicians begin to treat chronic hepatitis C more often and more
      aggressively, this potential problem with occur more frequently. Herein we
      reported a case of reactivation of sarcoidosis occurring during the treatment of
      chronic hepatitis C, and we present a literature review of other centers'
      experiences with this problem. Depending upon the severity of the exacerbation
      and the type of organ involvement, reactivation of sarcoidosis may require
      discontinuation of the interferon therapy, with or without the use of additional
      steroids. The majority of patients, however, do not require the use of steroids.
      Interestingly, continuation of the interferon therapy in the presence of a mild
      to-moderate exacerbation of sarcoidosis may be safe in a minority of patients
      with noncritical organ involvement.

PMID- 11824802
TI  - Biliary obstruction caused by intrabiliary transplantation from hepatocellular
      carcinoma.
AB  - A rare autopsy case of hepatocellular carcinoma (HCC) presenting as extrahepatic
      bile duct obstruction is reported. A 54-year-old man who had been treated at
      another hospital for obstructive jaundice was referred to our hospital and
      admitted on March 1, 1998, because of progressive jaundice. On hospital day 94,
      he died of bleeding esophageal varices. At autopsy, a bile duct tumor, measuring
      3.0 x 3.5 cm and adhering to the wall of the left hepatic duct, occluded the
      common hepatic duct at the hilus. A tumor measuring 2.0 x 2.0 cm was found in the
      parenchyma of the left liver lobe. The parenchymal tumor was not continuous with
      the extrahepatic bile duct tumor. Histologically, the bile duct tumor and the
      parenchymal tumor of the left lobe were diagnosed as HCC. The bile duct tumor was
      attached to the mucosa of the bile duct with a thin stalk. No invasive growth
      into the submucosa was observed. The tumor may have been an intrabiliary
      transplantation from the HCC in the left lobe via the bile duct.

PMID- 11824803
TI  - Malignant endocrine tumor of the pancreas associated with von Recklinghausen's
      disease.
AB  - We describe a case of malignant endocrine tumor of the pancreas associated with
      von Recklinghausen's disease. A 66-year-old woman with familial von
      Recklinghausen's disease was admitted to our hospital with weight loss and lower
      abdominal pain. Endoscopy revealed a submucosal tumor in the second part of the
      duodenum. Contrast-enhanced computed tomography showed a heterogeneous low
      density tumor, measuring 20 x 15 mm, in the head of the pancreas, and metastatic
      lymphadenopathy. Angiography showed faint tumor staining without encasement or
      apparent increase in vascularity. Pancreatoduodenectomy was performed.
      Macroscopically, there was a solid tumor, measuring 20 x 18 mm, in the head of
      the pancreas. Histologically, a malignant endocrine tumor was shown, with direct
      invasion to the duodenum, and lymph node metastases. This is the thirteenth case
      of pancreatic malignant tumor and the fourth case of pancreatic endocrine tumor
      associated with von Recklinghausen's disease reported in the world literature.

PMID- 11824804
TI  - Home lactulose enema: prevention of hepatic encephalopathy at home.

PMID- 11824805
TI  - Role of mucosal mast cells in Helicobacter pylori infection.

PMID- 11824806
TI  - Can DNA methylation be a molecular marker for eradication of Helicobacter pylori
      in MALT lymphoma?

PMID- 11824807
TI  - Simultaneous determination of quinapril and its active metabolite quinaprilat in
      human plasma using high-performance liquid chromatography with ultraviolet
      detection.
AB  - A high-performance liquid chromatography (HPLC) procedure for the simultaneous
      determination of quinapril and its active metabolite quinaprilat in human plasma
      samples is described. A one-step solid-phase extraction (SPE) with C18 cartridges
      was coupled with a reversed-phase HPLC system. The system requires two mobile
      phases composed of tetrabutyl ammonium hydrogensulfate (10 mM adjusted to pH 7)
      acetonitrile (62:38, v/v) for quinapril, and (25:75, v/v) for quinaprilat elution
      through a C18 Symmetry column and detection at a wavelength of 215 nm.
      Calibration curves were linear over the ranges 20 to 1,000 ng/ml for quinaprilat
      and 10 to 500 for quinapril. The limits of quantification were 20 and 10 ng/ml
      for quinaprilat and quinapril, respectively. Extraction recoveries were higher
      than 90% for quinapril and 80% for quinaprilat. This method has been successfully
      applied to a bioequivalence study of quinapril in healthy subjects.

PMID- 11824808
TI  - Identification of various urinary metabolites of fluorene using derivatization
      solid-phase microextraction.
AB  - A method for the qualitative analysis of various metabolites of fluorene is
      presented. The method uses solid-phase microextraction with an 85 microm
      polyacrylate fiber for extraction, headspace silylation with BSTFA and MTBSTFA
      without any catalyst for on-fiber derivatization and GC-MS in the selected ion
      monitoring mode for separation and detection. The suitability of the method for
      profile analysis of polycyclic aromatic hydrocarbon metabolites is shown by
      analyzing an urine of an occupationally exposed person after enzymatic cleavage
      of the excreted conjugates. Satisfactory separation of all investigated
      metabolites was achieved without interferences due to matrix peaks.

PMID- 11824810
TI  - Determination of fexofenadine in human plasma and urine by liquid chromatography
      mass spectrometry.
AB  - A sensitive method was developed to determine fexofenadine in human plasma and
      urine by HPLC-electrospray mass spectrometry with MDL 026042 as internal
      standard. Extraction was carried out on C18 solid-phase extraction cartridges.
      The mobile phases used for HPLC were: (A) 12 mM ammonium acetate in water and (B)
      acetonitrile. Chromatographic separation was achieved on a LUNA CN column (10 cm
      x 2.0 mm I.D., particle size 3 microm) using a linear gradient from 40% B to 60%
      B in 10 min. The mass spectrometer was operated in the selected ion monitoring
      mode using the respective MH+ ions, m/z 502.3 for fexofenadine and m/z 530.3 for
      the internal standard. The limit of quantification achieved with this method was
      0.5 ng/ml in plasma and 1.0 ng in 50 microl of urine. The method described was
      successfully applied to the determination of fexofenadine in human plasma and
      urine in pharmacokinetic studies.

PMID- 11824809
TI  - Determination of amiodarone and desethylamiodarone in human plasma by high
      performance liquid chromatography-electrospray ionization tandem mass
      spectrometry with an ion trap detector.
AB  - A sensitive and specific high-performance liquid chromatography-electrospray
      ionization-tandem mass spectrometry (HPLC-ESI-MS-MS) method has been developed
      for the simultaneous determination of amiodarone and desethylamiodarone in human
      plasma. After the addition of the internal standard tamoxifen, plasma samples
      were extracted using Oasis MCX solid-phase extraction cartridges. The compounds
      were separated on a 5 microm Symmetry C18 (Waters) column (150 x 3.0 mm, internal
      diameter) with a mobile phase of acetonitrile-0.1% forrmic acid (46:54, v/v) at a
      flow-rate of 0.5 ml/min. The overall extraction efficiency was more than 89% for
      both compounds. The assay was sensitive down to 1 microg/l for amiodarone and
      down to 0.5 microg/l for desethylamiodarone. Within-run accuracies for quality
      control samples were between 95 and 108% of the target concentration, with
      coefficients of variation <8%. The proposed method enables the unambiguous
      identification and quantitation of amiodarone and desethylamiodarone in both
      clinical and forensic specimens.

PMID- 11824811
TI  - Optimization of the separation lactic acid enantiomers in body fluids by
      capillary electrophoresis.
AB  - The optimization of the separation conditions of the two optical isomers of
      lactic acid by a factorial design is reported. Initially, different chiral
      selectors were systematically investigated and then a experimental design with
      three quantitative factors (cyclodextrin concentration and background buffer pH
      and concentration) were evaluated. Optimal conditions for obtaining a resolution
      higher than 1.5 were: phosphate buffer 200 mM at pH=6.0 with 413 mM 2
      hydroxypropyl-beta-cyclodextrin added (HP-beta-CD), 20 degrees C, -20 kV of
      applied potential and polyacrylamide-coated capillary. The method was validated
      for the measurement in plasma and it was applied to the identification of both
      isomers in body fluids such as urine, amniotic fluid and cerebrospinal fluid.
      Samples were centrifuged and diluted (1:4) prior to the analysis.

PMID- 11824812
TI  - Analysis of N-glycosylation of phospholipase A2 from venom of individual bees by
      microbore high-performance liquid chromatography-electrospray mass spectrometry
      using an ion trap mass spectrometer.
AB  - The N-linked oligosaccharides were released from the phospholipase A2 (PLA) with
      glycopeptidases and reductively aminated with the chromophore, p-aminobenzoic
      acid ethyl ester (ABEE). The ABEE-labeled oligosaccharides were separated by
      microbore high-performance liquid chromatography (micro-HPLC) using a reversed
      phase column and analyzed by electrospray mass spectrometry. Differentiation
      between alpha-1,3 and alpha-1,6 core-fucosylated glycans was achieved by
      comparison the glycans released by glycopeptidases peptide-N-glycanase A (PNase
      A) and peptide-N-glycanase F (PNase F). All N-linked oligosaccharides except 3B
      and 3C could be identified in this approach. The analysis of PLA oligosaccharides
      from the venom of individual bees indicated that glycosylation patterns between
      the younger and the older bees were similar.

PMID- 11824813
TI  - Development of a diphasic dialysis method for the extraction/purification of
      residues of ethinylestradiol in hair of cattle, and determination by gas
      chromatography-tandem mass spectrometry.
AB  - A confirmatory method for the analysis of ethinylestradiol extracted from cattle
      hair was developed. After the extraction of the xenobiotic from the hair, by
      using alkaline digestion, the purification of the extract was carried out by
      employing diphasic dialysis. For the optimization of the technique several
      parameters was evaluated such as pH, extraction solvents, temperatures, times and
      agitation speeds. The detection and confirmation of the steroid was accomplished
      by using a GC-MS2 ion trap system after trimethylsilylation. The calibration
      curve was linear over the range of 4-20 ng/g. The detection and quantification
      limit were 0.52 and 0.80 ng/g respectively; with recoveries up to 94%.

PMID- 11824814
TI  - Human nutritional supplements in the horse: comparative effects of 19
      norandrostenedione and 19-norandrostenediol on the 19-norsteroid profile and
      consequences for doping control.
AB  - The dietary supplements 19-norandrostenedione and 19-norandrostenediol are
      potential metabolic precursors of nandrolone. They are considered by law in the
      United States as prohormones without proven therapeutic, curative or diagnostic
      properties, and therefore available as over-the-counter drugs. Oral dosages of
      0.1-1 mg/kg body weight were readily absorbed in the equine intestinal tract and
      thereby led to urinary excretion of drastically increased 5alpha-estrane
      3beta,17alpha-diol conjugates, which are known to be final metabolites of
      nandrolone. The actual rules for detection of illicit nandrolone administration
      to the horse have been found applicable for the detection of surreptitious oral
      19-norandrostenedione and 19-norandrostenediol supplementation. Secondary markers
      of these administrations were high-level excretions of conjugated nandrolone,
      epinandrolone, 19-noretiocholanolone and 19-norepiandrosterone. No significant
      increase of circulating, biologically active nandrolone could be firmly
      evidenced, and it is therefore unclear to what extent continuous long-term
      administrations may have anabolic action.

PMID- 11824815
TI  - Opioid analgetics retention-pharmacologic activity models using biopartitioning
      micellar chromatography.
AB  - Opioids are drugs used in medicine for pain control. In this paper, retention
      pharmacokinetics and retention-pharmacodynamics relationships of opioids are
      proposed and statistically validated. These models are based on the compound
      retention in the biopartitioning micellar chromatography system (BMC), a new
      methodology which has successfully been used to develop QRAR models for many
      other families of compounds. The obtained results are compared to the traditional
      QSAR models using lipophilicity data. The adequacy of QRAR models is due to the
      fact that the characteristics of the compounds such as the hydrophobicity,
      electronic charge and steric effects determine both their retention in BMC and
      their pharmacokinetic and pharmacodynamic behavior.

PMID- 11824816
TI  - Determination of polychlorinated biphenyls in small-size serum samples by solid
      phase extraction followed by gas chromatography with micro-electron-capture
      detection.
AB  - An new method for the determination of polychlorinated biphenyls (PCBs) in serum
      samples of up to 1 ml has been developed. The procedure consisted in the solid
      phase extraction (SPE) of the analytes on an Oasis cartridge and the subsequent
      on-line elimination of the fat by directly dropping of the eluate from the SPE
      cartridge on a multilayer column placed below the cartridge. This configuration
      allowed minimising of the sample manipulation as well as the time, solvent and
      sorbent consumption (i.e. complete sample preparation can be accomplished in
      about 1 h with only 3 ml of toluene and 300 mg of silica). The SPE plus clean-up
      method developed showed a satisfactory performance for the analysis of PCBs in
      rat serum samples providing similar recoveries (i.e. range 73-128% for most of
      the congeners selected) at the different spiking levels investigated (1.25, 0.50
      and 0.25 ng/ml). Detection limits using a microelectron capture detector were in
      the range 0.01-0.30 ng/ml of serum and the relative standard deviations of the
      complete method better than 18% irrespective of the PCB concentration. The
      validated method has been applied to the evaluation for the first time of the PCB
      levels in serum samples of up to 1 ml from individuals of an Egyptian Vulture
      colony in Spain.

PMID- 11824817
TI  - Rapid determination of pseudoephedrine in human plasma by high-performance liquid
      chromatography.
AB  - A rapid high-performance liquid chromatographic method for the quantitation of
      pseudoephedrine in human plasma is presented. The sample preparation involved
      liquid-liquid extraction of pseudoephedrine from alkalised plasma with hexane
      isoamylalcohol (9:1, v/v) and back-extraction of the drug to 0.02 M hydrochloric
      acid. Liquid chromatography was performed on an octadecylsilica column (50 x 4
      mm, 5 microm particles); the mobile phase consisted of acetonitrile-phosphate
      buffer containing 0.1% of triethylamine, pH 2.4 (5:95, v/v). The run time was 4
      min. The spectrophotometric detector was operated at 195 nm. Codeine was used as
      the internal standard. The limit of quantitation was 5.8 ng/ml using 0.5 ml of
      plasma. Within-day and between-day precision expressed by relative standard
      deviation was less than 7% and inaccuracy did not exceed 8%. The assay was
      applied to the analysis of samples from a pharmacokinetic study.

PMID- 11824818
TI  - Determination of lonazolac and its hydroxy and O-sulfated metabolites by on-line
      sample preparation liquid chromatography with fluorescence detection.
AB  - A reliable method, which can be used for the determination of lonazolac and its
      hydroxylated and O-sulfated metabolites in cell culture media with
      methyllonazolac as the internal standard is described. The procedure employs on
      line sample enrichment using a BioTrap 500 MS (20 x 4 mm I.D.) extraction pre
      column and subsequent gradient separation on an Xterra MS C18-HT (100 x 3 mm
      I.D., 3.5 microm particles) analytical column in the back-flush mode. Signal
      monitoring was done by measurement of fluorescence responses at 273 nm for
      excitation and 385 nm for emission. Structural identity of analyte peaks was
      confirmed by liquid chromatography coupled to mass spectroscopy (LC-MS-MS) using
      an electrospray ionization (ESI) source in the selected reaction monitoring (SRM)
      mode. Mean recoveries of lonazolac, hydroxylonazolac and lonazolac sulfate,
      respectively, from the biological matrix were 104.2 +/- 3.5, 96.7 +/- 2.2, and
      100.9 +/- 3.5%. The limit of detection (LOD) for the three compounds was about 5
      ng/ml using a total sample volume of only 50 microl. Linearity of signal
      responses versus concentration for all three analytes was accomplished in the
      range 10-600 ng/ml. The mean values of the coefficients of variation (CV) for
      quality control samples measured in duplicate at three different days at the 10,
      40, 100, and 400 ng/ml level were 4.46 +/- 1.15, 3.94 +/- 2.13 and 4.79 +/- 2.07%
      for lonazolac, hydroxylonazolac and lonazolac sulfate. The target analytes were
      sufficiently stable at both storage and sample preparation conditions because no
      substantial deviations between analyte concentrations measured before and after
      subsequently performed freeze and thaw cycles were observed.

PMID- 11824819
TI  - Determination of amprenavir, a HIV-1 protease inhibitor, in human seminal plasma
      using high-performance liquid chromatography-tandem mass spectrometry.
AB  - A HPLC-MS-MS method to measure amprenavir in human seminal plasma has been
      developed and validated. The procedure uses stable, isotopically labeled 13C6
      amprenavir as an internal standard and 100 microl of sample. The method is
      accurate (bias less than or equal to 7.2%) and precise (within- and between-day
      RSDs less than or equal to 4.2%) over the dynamic range of 30-4,000 ng/ml.
      Recently, this simple and sensitive method was used to determine amprenavir
      concentrations in seminal samples collected from HIV-1 positive subjects
      receiving amprenavir antiretroviral therapy as part of a multicenter clinical
      trial.

PMID- 11824820
TI  - Identification of metabolites of fluorine-18-labeled M2 muscarinic receptor
      agonist, 3-(3-[(3-fluoropropyl)thio]-1,2,5-thiadiazol-4-yl)-1,2,5,6-tetrahydro-1
      methylpyridine, produced by human and rat hepatocytes.
AB  - An accurate, rapid method for the determination of unmetabolized 3-(3-[(3
      [18F]fluoropropyl)thio]-1,2,5-thiadiazol-4-yl)-1.2,5,6-tetrahydro-1
      methylpyridine (FP-TZTP), a selective M2 muscarinic agonist, is necessary in
      order to obtain quantitative information from positron emission tomography (PET)
      imaging. Using LC-MS-MS to analyze products from cultured human and rat
      hepatocytes, we identified metabolites resulting from oxidation of the nitrogen
      in the tetrahydropyridine ring, sulfur-oxidation, demethylation of the tertiary
      amine, and oxidation of the tetrahydropyridine ring. From the knowledge of the
      structure of the metabolites, we have developed a two-step extraction sequence
      that allows rapid determination of the parent fraction in plasma without time
      consuming chromatographic analysis.

PMID- 11824821
TI  - Simultaneous measurement of zolmitriptan and its major metabolites N
      desmethylzolmitriptan and zolmitriptan N-oxide in human plasma by high
      performance liquid chromatography with coulometric detection.
AB  - Zolmitriptan, N-desmethylzolmitriptan, zolmitriptan N-oxide and an internal
      standard (an analogue of zolmitriptan) were extracted from plasma by a solid
      phase extraction (SPE). Chromatography was performed using isocratic reversed
      phase high-performance liquid chromatography (HPLC) with coulometric end-point
      detection. The standard curves were linear over the range 2-20 ng/ml for
      zolmitriptan and its metabolites in plasma. The mean inter- and intra-assay
      coefficients of variation over the range of the standard curves were less than
      11%. The absolute recovery averaged 87, 58 and 77% for zolmitriptan. N
      desmethylzolmitriptan and zolmitriptan N-oxide, respectively. The assay
      sensitivity was 0.5 ng for each analyte.

PMID- 11824822
TI  - High-performance liquid chromatographic analysis of angiotensin II receptor
      antagonist valsartan using a liquid extraction method.
AB  - PURPOSE: To develop an easy assay for the quantitation of the angiotensin II
      receptor antagonist valsartan in human plasma using a liquid extraction
      procedure. METHOD: The method involves acid extraction from 1 ml human plasma
      with methyl-tert.-butyl ether followed by back-extraction into a basic medium. An
      isocratic HPLC equipped with reverse phase column and a fluorescence detector was
      used at room temperature. RESULTS: The response to 10-2000 ng/ml valsartan was
      linear. In plasma of three human subjects given 160 mg valsartan orally,
      concentrations of 25-1540 ng/ml were observed. CONCLUSION: This convenient method
      is suitable for pharmacokinetic studies of valsartan.

PMID- 11824823
TI  - Analysis of alpha-amylase-derived pyridylamino-dextran sulfate oligomers by the
      combination of size-exclusion and reversed-phase high-performance liquid
      chromatography.
AB  - In a previous study, we reported a novel method for the separation and
      quantification of a strong negatively charged material, dextran sulfate sodium
      (DSS), using fluorometric labeling with 2-aminopyridine and size-exclusion high
      performance liquid chromatography. In the present study, we developed a method
      for the separation of pyridylamino-DSS (PA-DSS) using reversed-phase high
      performance liquid chromatography (RPLC). In vitro enzymatic degradation of the
      PA-DSS was carried out using alpha-amylase. In RPLC, depolymerized PA-DSS was
      eluted on the basis of molecular mass (in the order pentamer, trimer, dimer, and
      monomer of PA-DSS) and separations were more sharply than in size-exclusion
      chromatography. The combination of RPLC and size-exclusion chromatography also
      separated depolymerized PA-DSS as effectively as RPLC alone.

PMID- 11824824
TI  - Effects of sample storage on 7- and 8-dehydrocholesterol levels analysed on whole
      blood spots by gas chromatography-mass spectrometry-selected ion monitoring.
AB  - Smith-Lemli-Opitz syndrome (SLOS) patients have increased 7- and 8
      dehydrocholesterol (DHC) concentrations. Using gas chromatography-mass
      spectrometry with selected ion monitoring we investigated whether storage time
      (24 h, 7 and 30 days, and 22 months at room temperature or at 4 degrees C)
      affected DHC concentrations in whole blood spots (WBSs) from SLOS patients and
      normal controls. Our results suggest that WBS sterol analysis can be used for
      SLOS screening and possibly related inborn errors of sterol metabolism with a
      100% sensitivity and specificity on specimens stored for up to 30 days, either at
      room temperature or 4 degrees C. After 22 months of storage at both temperature
      SLOS samples can be indistinguishable from control samples. Therefore, great
      caution should be used to exclude SLOS by sterol analysis of WBSs stored for a
      long time.

PMID- 11824825
TI  - National distribution of chemical concentrations in mussels and oysters in the
      USA.
AB  - Since 1986 the NOAA National Status and Trends (NS&T) Program Mussel Watch has
      monitored concentrations of trace chemicals in the coastal United States by
      sampling mussels, oysters, and sediment. The sediment data have been used to
      define the status or geographic distribution of chemical concentrations
      (Daskalakis, K. D., & O'Connor, T. P. (1995). Distribution of chemical
      contamination in coastal and estuarine sediments. Marine Environmental Research
      40, 381-398) and the molluscan data have provided an estimate of temporal trends
      (O'Connor, T. P. (1996). Trends in chemical concentrations in mussels and oysters
      collected along the US coast from 1986 to 1993. Marine Environmental Research
      41,183-200, O'Connor, T. P. (1998). Mussel Watch results from 1986 to 1996.
      Marine Pollution Bulletin 37, 14-19). This paper centers on chemical
      concentrations in mollusks at 263 sites around the United States. It provides
      perspective on concentration ranges and on geographic distributions. For most
      organic chemicals and lead, concentrations vary in proportion to numbers of
      people living near a site. For elements, other than lead, high concentrations in
      mollusks can be due more to natural factors than to human activity.
      Concentrations of PAHs in tissues of mussels from urban areas are in a range
      reported to exert biological responses.

PMID- 11824826
TI  - Relating the reproductive toxicity of five ingested metals in calanoid copepods
      with sulfur affinity.
AB  - The sublethal toxicity of dietary Ag, Cd, Hg, Mn, and Zn to marine copepods,
      measured as depressed egg production, was evaluated as a function of ambient
      metal concentrations and metal concentrations in copepod tissues. All metals were
      toxic following 4-h feedings on metal-contaminated phytoplankton food, but there
      was a four order of magnitude difference between the inhibitory concentration in
      copepod tissues of the most toxic (2.4 nmol g(-1) dry wt. for Hg) and least toxic
      (13.4 micromol g(-1) dry wt. for Mn) metals. Metal concentrations in copepods
      that elicited a toxic response were about 3 times higher than background
      concentrations for Ag and 9 times higher for Hg, about 2 times higher for Cd, two
      orders of magnitude higher for Mn, and only 5% higher for Zn. Copepods exposed to
      lower concentrations of Zn for longer periods (1 week), resulting in tissue Zn
      concentrations similar to those in the short-term exposures, were not affected,
      suggesting that copepods were capable of adjusting to slowly increasing Zn by
      sequestration of this metal. Toxic metal concentrations in copepod tissues were
      directly proportional (r2 = 0.85) to the affinity of the metals for sulfur, as
      indicated by the solubility products of the metal sulfides. This relationship,
      together with protein analysis of eggs, published recently, suggests that metals
      affect egg production by binding to enzymes involved with vitellogenesis.

PMID- 11824827
TI  - Using trace elements in skin to discriminate the populations of minke whales in
      southern hemisphere.
AB  - Concentrations of 12 trace elements (V, Cr, Mn, Cu, Zn, Se, Rb, Sr, Cd, Cs, Ba,
      and Hg) were determined in liver and skin tissues of minke whales from various
      regions within the Antarctic Ocean. Cd concentrations in livers of southern minke
      whale were apparently higher than those in cetaceans from other regions, while Hg
      concentrations were lower. There were significant positive correlations between
      body length and concentrations of Cd and Hg in the liver. The concentrations of
      all trace elements in the skin were lower than those in other cetaceans reported
      previously. Significant positive correlations between liver and skin were found
      for Cr, Mn, Cu, Zn, Rb, Cd, and Cs, implying that the concentrations of these
      trace elements in the skin reflect those of internal organs. Large interannual
      variation of the accumulation pattern of trace elements in the skin was observed
      for the southern minke whales from Area V. There were significant differences in
      the skin element concentrations among Areas III, IV, and V, especially for males.
      Also, discriminant analysis between geographically two different groups collected
      during 1995/1996 austral summer season, based on the concentrations of trace
      elements in the skin, allowed for a correct classification of 90% of these minke
      whales. These results suggest that measurement of trace elements in skin samples
      could provide valuable information on the status of contamination and possible
      geographic differences in the accumulation levels in southern minke whales.

PMID- 11824828
TI  - Food intake and body measurements of Atlantic bottlenose dolphins (Tursiops
      truncates) in captivity.
AB  - The food consumption (recorded in kg of individual fish species), body length and
      mass of 11 Atlantic bottlenose dolphins kept first at Windsor Safari Park, UK
      (1979-1993/1994), and later at Harderwijk Marine Mammal Park, The Netherlands
      (1993/1994-1995) are reported. This broad-scale, longitudinal study is based on
      historical data that were originally recorded for short-term husbandry purposes.
      The chemical composition and caloric value of the diet were variable and were not
      recorded. The food intake quantities should therefore be viewed as rough weight
      estimates of what wild conspecifics might eat (depending on their diet). The
      average annual food consumption of adult males and non-pregnant, non-lactating
      females was approximately 2000 kg of fish (estimated at 176 x 10(5) kJ). Food
      consumption showed little increase during gestation, but was 58-97% higher during
      lactation than during similar periods in non-reproductive years. All six calves
      began to eat solid food within a year of birth although suckling continued for 14
      37 months after birth. The pattern of food intake of mothers and calves varied
      substantially between suckling periods. No seasonal changes in food consumption
      were detected, although there were small seasonal changes in water temperature.
      Births occurred at various times of year, since the timing of mating varied
      between years. The animals' body length increased rapidly during the first 3
      years of life after which the growth rate decreased. Body length reached
      asymptote at approximately 270 cm. Adults of both sexes weighed around 260 kg.
      The relationship between standard body length (in cm) and body mass (in kg),
      although based on a small sample size (n = 16), can be expressed as body mass =
      17.261e(0.0156(body length-100)). Animals weighing 155-225 kg consumed between 2
      and 4% of their body mass per day.

PMID- 11824829
TI  - Methodological aspects in the assessment of severity of depression by the
      Hamilton Depression Scale.
AB  - Observer-rating scales are used for the evaluation of drug trials in depression.
      One of the most widely used depression rating scales is still the Hamilton
      Depression Scale (HAMD), which was developed at the time when the first
      antidepressants were becoming available. Due to its construction it seems to have
      a specific focus on drug effects of classical antidepressants. As a result of
      different methodological analyses such as principal component analysis, the Rasch
      model and facet analysis, a differentiation between core symptoms reflecting the
      severity of depression and additional symptoms describing other aspects of the
      symptomatology of depression seems meaningful. The use of the HAMD 6-item score,
      described primarily by Bech, as the main efficacy criterion in antidepressant
      drug trials gives a fair estimation of drug-induced changes of severity of
      depression and avoids bias such as the well-known bias of the HAMD total score in
      favour of tricyclic antidepressants. This is demonstrated by the evaluation of
      two sertraline-amitriptyline comparative studies.

PMID- 11824830
TI  - Identification of items which predict later development of depression in primary
      health care.
AB  - To improve recognition and treatment of depression in primary care it would be
      advantageous to have criteria for identification of later depression. Only a few
      studies were performed on primary care samples to examine risk factors for new
      depressive episodes. These were mostly cross-sectional and did not include
      psychiatric symptoms as possible predictors. This is the first one-year-follow-up
      study investigating prospectively psychiatric symptomatology as risk factors for
      depressive episodes in a primary care sample. An international primary care
      sample of initially non-depressed subjects (n = 2,445) was examined for the
      presence of depression (ICD-10) at follow-up. Initial measures addressed presence
      of psychiatric symptoms according to the CIDI-Primary Health Care Version and
      sociodemographic variables. Logistic regression analysis was carried out to
      determine the relationship with the development of new depressive episodes. After
      one year, 4.4% of primary care patients met ICD-10 criteria for a depressive
      episode. Logistic regression analysis revealed that symptoms of depression and
      physical, mainly pain-related symptoms were associated with depression at follow
      up. General practitioners therefore should be careful in the consideration of
      depressive symptoms but also of somatic complaints which might precede depression
      or mask depressive symptomatology. The present results might be helpful for
      future development of prediction scales.

PMID- 11824831
TI  - Validity of the five-item WHO Well-Being Index (WHO-5) in an elderly population.
AB  - BACKGROUND: Depression has a high prevalence in the elderly population; however
      it often remains undetected. The WHO 5-item Well-Being Index (WHO-5) is a short
      screening instrument for the detection of depression in the general population,
      which has not yet been evaluated. The goals of the present study were: 1) to
      assess the internal and external validity of WHO-5 and 2) to compare the two
      recent versions of WHO-5. STUDY POPULATION AND METHODS: 367 subjects above 50
      years of age were examined with the WHO-5. ICD-10 diagnoses were made using a
      structured interview (CIDI). The internal validity of the well-being index was
      evaluated by calculating Loevinger's and Mokken's homogeneity coefficients.
      External validity for detection of depression was evaluated by ROC analysis.
      RESULTS: The scale was sufficiently homogeneous (Loevinger's coefficient: version
      1 = 0.38, version 2 = 0.47; Mokken coefficient > 0.3 in nearly all items). ROC
      analysis showed that both versions adequately detected depression. Version 1
      additionally detected anxiety disorders, version 2 being more specific for
      detection of depression. CONCLUSION: The WHO-5 showed a good internal and
      external validity. The second version is a stronger scale and was more specific
      for the detection of depression. The WHO-5 is an useful instrument for
      identifying elderly subjects with depression.

PMID- 11824832
TI  - Mental health: diversities, possibilities, shortcomings, challenges. the WHO
      perspective.

PMID- 11824833
TI  - Quality of life: a dimension in multiaxial classification.
AB  - The study provides an overview of the historical aspects of multiaxial
      classification. Particular reference is paid to the multiaxial formats of ICD-10,
      DSM-IV and the WPA International Guidelines for Diagnostic Assessment (IGDA). The
      IGDA proposes a tetraaxial format with quality of life as one axis as well as an
      axis on symptomatology, an axis on adaptive functioning and an axis on
      environmental/psychosocial conditions. The axis on quality of life is added in
      recognition of the increasing importance placed upon the patient's perception of
      his/her capacity of self fulfillment and the attention paid to quality of life as
      a major descriptor of health status as well as an outcome measure of clinical
      care.

PMID- 11824834
TI  - Current status of quality of life assessment in schizophrenic patients.
AB  - Though the need to evaluate the quality of life of schizophrenic patients is well
      recognized, there are significant issues that remain unsolved. Are these patients
      capable of judging their own quality of life or does their illness invalidate
      their responses? Are there any psychometrically valid instruments that enable us
      to assess quality of life in these patients? When should quality of life be
      assessed in schizophrenics? While the ERIQA European Group completes their work
      and provide us with some common guidelines concerning quality of life assessment
      in medicine, this article provides some simple action guidelines regarding these
      questions. These guidelines are the result of analyzing the most up-to-date
      literature in the field. It also takes a brief look at the most universally used
      tools.

PMID- 11824835
TI  - Concurrent psychiatric comorbidity and multimorbidity in a community study:
      gender differences and quality of life.
AB  - This study analysis of a community cohort at the age of 35 focused on the effects
      of gender and multimorbidity on quality of life and subjective distress.
      Consistent with an earlier analysis, quality of life decreased with increasing
      numbers of concurrent psychiatric diagnoses. Women generally reported lower
      quality of life and higher distress than men. Relative to men, well-being in
      women was subject to more diagnostic (alcohol abuse/dependence, depression,
      generalized anxiety disorder, bulimia) and social influences (partner,
      promotion). The same factors predicted women's psychological and physical well
      being, indicating a more holistic experience in women. Men's physical well-being
      did not correlate with any of the diagnostic or social variables measured.

PMID- 11824836
TI  - Assessment of subclinical symptoms and psychological well-being in depression.
AB  - A substantial body of research suggests that subclinical symptoms characterize
      the longitudinal course of major depression and have important pathophysiological
      and treatment implications. Specific treatment of residual symptoms may in fact
      improve longterm outcome, by acting on those residual symptoms that progress to
      become prodromes of relapse. The assessment of psychological well-being is also
      important, since its absence may create conditions of vulnerability to possible
      adversities. The route of recovery, thus, lies not exclusively in alleviating the
      negative, but in engendering the positive.

PMID- 11824837
TI  - Prospective studies of cothymia (mixed anxiety-depression): how do they inform
      clinical practice?
AB  - We suggest that the diagnosis of mixed anxiety depression at syndromal level
      (i.e. both anxiety and depressive diagnoses present in the same person and given
      equal status) is valuable clinically and should be introduced into the formal
      classification of neurotic and mood disorders. Evidence is given from a
      systematic review that cothymia has a significantly worse outcome than either an
      anxiety or a depressive diagnosis alone (p < 0.0001). Long-term follow-up data in
      a 12-year outcome study of neurotic disorder reinforce this finding both with
      regard to social functioning and the clinical course of anxiety and depressive
      disorders; these were significantly worse (P < 0.001 and P < 0.02 respectively)
      in those with cothymia compared with single anxiety disorders. These outcome
      differences are much greater than those between anxiety and depressive disorders
      alone.

PMID- 11824838
TI  - Late life depression.
AB  - Depression has an overall prevalence of 5-8%. The prevalence of late life
      depression is estimated among people 65 years of age to be 15%. There is a great
      under-diagnosis and under-treatment of late life depression with the most serious
      consequence being premature death. Depression is also an important and
      independent risk factor for mortality following myocardial infarction, while
      patients with stroke associated with depression also have a higher death rate.
      The suicide rate is increased in elderly especially elderly men with depression.
      The aetiology of depression is more heterogeneous than depression in younger
      adults. Obviously age-related changes in the brain increase the risk for
      depression. Patients with neurodegenerative disorders also run a higher risk for
      being depressed. In Alzheimer's disease the frequency is around 50%. Deficiency
      of essential nutrients like folic acid and vitamin B12 is an obvious risk factor
      for both disorders with cognitive impairment and depression. Treatment of
      depression in the elderly follows the same lines as treatment of depression in
      younger patients. Many different drugs may be prescribed; however, the risk of
      adverse events is greater in the elderly. The drugs of choice are the selective
      serotonin re-uptake inhibitors (SSRIs), which have a response rate of around 65%.
      Of interest is that emotional disturbances like irritability, aggressiveness and
      anxiety also respond to treatment with SSRIs. A comprehensive treatment of late
      life depression, which includes social and psychological support, has a response
      rate of 80-90%.

PMID- 11824840
TI  - Diagnosis and treatment of rapidly cycling bipolar disorder.
AB  - The conceptualization of rapidly cycling bipolar disorder remains controversial.
      The DSM-IV definition of rapid cycling, although very reliable, may be not
      sufficiently inclusive (i.e., it may exclude patients with very short episodes of
      very high frequency, who are very typical in terms of external validators, and
      are currently regarded as rapid cyclers by many researchers and clinicians).
      Moreover, the addition of the requirement of pole switching (i.e., at least one
      direct transition from one polarity of mood to the other) during the previous
      year may increase the prognostic and treatment response implications of the
      diagnosis of rapid cycling. It is commonly held that rapid cyclers are refractory
      to lithium prophylaxis. However, currently available research evidence suggests
      that lithium prophylaxis does exert an impact on the course of rapidly cycling
      bipolar disorder. One double-blind crossover study supports the clinical
      impression that the combination of at least two mood stabilizers may be needed in
      most rapid cyclers.

PMID- 11824839
TI  - Standardizing the Hamilton Depression Rating Scale: past, present, and future.
AB  - The Hamilton Depression Rating Scale (HAM-D) has become the most widely used
      depression severity rating scale in the world. It was originally published by Max
      Hamilton in 1960 to measure severity of depression in previously diagnosed
      depressed inpatients. Since that time, multiple versions of the scale have been
      created, although authors are rarely clear about which version they used. In
      addition, structured interview guides, self-report forms, and computerized
      versions have been developed in an effort to standardize administration of the
      scale and improve the psychometric characteristics of the individual items. The
      history of the development of these features is discussed, and the various
      versions of the scale are summarized in tables. This article is a fitting tribute
      to Per Bech, who has contributed so much to the assessment of depression
      severity.

PMID- 11824841
TI  - Limitations in randomised controlled trials evaluating drug effects in mania.
AB  - Considering the increasing number of drugs evaluated for mania in randomised
      controlled trials (RCTs) and the potential discrepancies between recommendations
      based on RCTs and the antimanic treatment given in clinical practice, this paper
      addresses some issues related to RCTs on drug effects in mania. One major
      question raised in the paper is to what extent selection prior to the point of
      randomisation in RCTs in mania may limit the applicability of study results to
      patients seen in ordinary clinical practice. Although such limitations in
      generalisability can be difficult to investigate empirically, it is emphasised
      that they should be openly discussed in the reports of RCTs. Another major focus
      is the issue of evaluation and interpretation of outcome, including a discussion
      of various response criteria based on mania rating scale scores. It is pointed
      out that essential criteria of dimensionality have only been sufficiently
      evaluated for the Bech-Rafaelsen Mania Rating Scale, although the fulfilment of
      such criteria are prerequisites for adding up the item scores to a total score
      reflecting the severity of mania. It is suggested that response defined as a
      decline in mania score below a certain limit may have some advantages over the
      commonly used 50% reduction criterion. The issues arising from the unusual high
      drop-out rates of around 50% are also addressed. Despite the fact that we need
      rigorous placebo-controlled trials to establish antimanic efficacy of new
      compounds, we also need large scale pragmatic studies using broad inclusion
      criteria, comparing the various treatments, alone or in combination, to
      investigate how they work in clinical practice. These studies maybe randomised
      but open and use simple but relevant outcome measures.

PMID- 11824842
TI  - Arguments for the specificity of the antisuicidal effect of lithium.
AB  - Affective disorders are characterized by first a high recurrence risk, second a
      30-50 times increased suicide risk and third a 2- to 3 times increased overall
      mortality. In contrast to a populistic belief no scientific evidence exists that
      antidepressant treatment, particularly long-term treatment, could reduce the the
      risk of suicidal acts in depressive patients with a history of suicide attempts.
      Data, however, coming from international, systematic, retrospective analyses of
      well-documented long-term courses of illness in reliably diagnosed patients, and
      from a large national, prospective long-term trial on the prophylactic efficacy
      of lithium versus carbamazepine and amitriptyline has accumulated in the last 10
      15 years strongly supporting a (possibly specific) antisuicidal effect of
      lithium. The large collaborative IGSLI study (International Group for the Study
      of Lithium-treated Patients) covering 5,616 patient years clearly showed that
      adequate long-term lithium treatment significantly reduces and even normalizes
      the excess mortality of patients with affective disorders. A metaanalysis on
      17,000 patients pooled from 28 studies demonstrated that the rate of suicidal
      acts is 8.6 fold higher in patients without lithium as compared to those with
      regular lithium treatment. A post-hoc analysis of a large multicenter, controlled
      long-term trial found no suicidal acts in 146 patients randomized to lithium
      compared to 9 suicidal acts in 139 patients randomized to carbamazepine.
      Reanalysis of the data from the IGSLI study supports the concept of the
      specificity of lithium, i.e., evidence could be provided that lithium also
      reduces suicidal behavior in patients who do not benefit from the lithium
      treatment in terms of episode reduction. CONCLUSION: Lithium has to be considered
      as a first line mood stabilizer in affective disorders, particularly in patients
      with a history of suicide attempts. Extreme caution is required when lithium is
      discontinued or a patient is switched to another mood stabilizer, because such a
      patient might have been protected against suicidal impulses in spite of an
      incomplete response as to the number and quality of depressive/manic episodes.

PMID- 11824843
TI  - Imaging the serotonergic system in depression.
AB  - Positron emission tomography (PET) and single photon emission computed tomography
      (SPECT) allow for the in vivo visualisation and measurement of, e.g. the
      serotonergic system in the brain of depressed patients. Currently, the available
      ligands permit the investigation of 5-HT2A and 5-HT1A receptors, the serotonin
      transporter and serotonin synthesis. 5-HT2A receptors have most extensively been
      investigated and increases, decreases or no differences in ligand binding have
      been found. Previous treatment and suicidality could be major confounding
      variables. Tricyclics seem to decrease ligand binding, while SSRIs in most
      studies increase ligand binding. A few studies have looked at the 5-HT1A receptor
      and demonstrated decreases in binding. The one study which looked at the effect
      of an SSRI treatment did not find any effect. The serotonin transporter
      availability seems to be reduced in depression. Tryptophane depletion studies
      have demonstrated effects on brain metabolism in serotonin related regions and on
      5-HT2A receptors. Finally, serotonin synthesis studies have shown interesting
      differences between males and females.

PMID- 11824844
TI  - Hippocampal damage mediated by corticosteroids--a neuropsychiatric research
      challenge.
AB  - There is an increasing evidence that corticosteroids damage the hippocampus in
      rodents and in primates. Hippocampal atrophy induced by corticosteroids may play
      an important role in the pathogenesis of a range of neuropsychiatric disorders.
      Hippocampus is necessary for short-term memory consolidation and HPA axis
      regulation. Signs of hippocampal damage (HPA dysregulation in combination with
      memory impairment) are found in affective disorders, Alzheimer's disease and in
      posttraumatic stress disorder. MRI volumetry reveals reduced hippocampal volume
      in these diseases. Evidence supporting the "glucocorticoid hypothesis" of
      psychiatric disorders is reviewed in the first part of the paper. Unresolved
      questions concerning temporary aspects of neurodegeneration, causality,
      reversibility, type of damage, factors increasing hippocampal vulnerability, and
      both pharmacological (CRH antagonists, antiglucocorticoid drugs, GABA-ergic,
      serotonergic, glutamatergic agents) and non-pharmacological (psychotherapy)
      treatment approaches are discussed in the second part.

PMID- 11824845
TI  - Schizophrenia and substance misuse problems: a comparison between patients with
      and without significant carer contact.
AB  - AIM: Many researchers and clinicians in the mental health field have given much
      attention over the last few years to patients with co-morbid problems of
      schizophrenia and substance use. This population is becoming a focus of attention
      for all service providers owing to the suggested increase in numbers of patients
      with these dual diagnoses and the observed negative effects on patients and costs
      to services. The advantages for providing family interventions in schizophrenia
      are now well established and increasingly these interventions are being evaluated
      for families of dual diagnosis patients. Many dually diagnosed patients do not,
      however, have a great deal of contact with a carer/relative. This paper looks at
      whether differences exist between patients with a dual diagnosis that have carer
      contact and those who do not have carer contact in terms of their illness history
      and type of substance use. For the purpose of this article 'carer' refers to an
      individual who is an informal carer or relative with whom the client has weekly
      contact of 10 h. Many of these carers provide the client with emotional, physical
      and material support. METHOD: The identification process for both'carer contact'
      and 'no carer contact' patients was conducted through the screening of the
      hospital's care programme approach (CPA) lists and through contact with care
      coordinators and consultants. Case notes of all patients identified were screened
      and information on demographic data, duration of illness, admissions and
      substance use was collected. RESULTS: Results indicated that the 'no carer
      contact' group was older and had significantly more days in hospital at last
      admission. CONCLUSIONS: It is possible that as patients get older their contact
      with significant others decreases, i. e. loss of contact with key relatives is
      due to age rather than severity of substance use. Furthermore, patients' reduced
      contact results in them having longer stays in hospital possibly because they
      will not receive additional support when discharged.

PMID- 11824846
TI  - Patient satisfaction and ward atmosphere during a crisis in an open psychiatric
      ward.
AB  - BACKGROUND: There is great need for useful indicators of quality of care for
      inpatient psychiatric treatment. The study examines whether patient satisfaction
      and ward atmosphere can be used as a means of evaluating an assumed decline in
      quality of care during a crisis in an open psychiatric ward. METHODS: Twice a
      year for 2 years ten patients filled out a standardized patient satisfaction
      questionnaire developed by the Swedish Institute for Health Services Development
      (SPRI) on their day of departure. At the same time all the patients in the ward
      evaluated the ward atmosphere using the Ward Atmosphere Scale (WAS). In the third
      study period the ward went through a crisis where quality of care was expected to
      be lower. RESULTS: The SPRI questionnaire confirmed the decline in patients'
      perceived quality of care on six of 41 questions, WAS was markedly lower on five
      of ten subscales. CONCLUSIONS: Both WAS and the SPRI questionnaire gave useful
      information on how the ward was affected by the crisis. WAS seemed to be a more
      sensitive way of measuring quality of care, while the SPRI questionnaire
      indicated more clearly the practical consequences.

PMID- 11824847
TI  - Urban birth and migrant status as risk factors for psychosis: an Australian case
      control study.
AB  - BACKGROUND: Urban birth and migrant status have been identified as risk factors
      for psychosis in North American and European studies. The aim of this study was
      to explore these variables in an Australian case-control study. METHOD: Country
      of birth of subjects and their parents, and place of birth of Australian-born
      subjects, were examined in individuals with psychosis drawn from a prevalence
      study (n = 310) and well controls recruited from the same catchment area (n =
      303). RESULTS: Migrant status was associated with a significantly decreased odds
      of having a psychotic disorder. For those born in Australia, neither migrant
      status of parents nor urban birth was associated with having a psychotic
      disorder. CONCLUSIONS: The lack of effect for urban birth and second-generation
      migrant status may help generate candidate environmental risk factors that
      operate in Europe but not in Australia.

PMID- 11824848
TI  - Early psychosis in the inner city: a survey to inform service planning.
AB  - BACKGROUND: In recent years, there has been a growing impetus to offer services
      for people with early psychosis. This paper describes a survey undertaken as the
      basis for the development of an early psychosis service. Rates of psychosis are
      known to differ between cities and rural areas and between ethnic groups.
      Identifying service needs is enhanced if the social and demographic
      characteristics, as well as the incidence, of people with psychosis in a given
      catchment area are known. METHOD: The present study identified all presentations
      of people aged 16 or over with first and second episodes of psychosis in a 6
      month period within a specified South London catchment area.A follow-up was
      carried out at 1 year. RESULTS: This survey confirmed existing knowledge on the
      social and service needs of this population, in finding high rates of
      unemployment and homelessness, poor engagement with services and frequent
      involuntary pathways to mental healthcare. Subgroups were also identified with
      specific needs, which are less often cited in the literature, such as groups of
      asylum seekers and people with young dependants. CONCLUSIONS: The results of the
      survey indicated that existing services were not adequately meeting the needs of
      people with early psychosis. They have been used to inform the development of an
      innovative service for people with early psychosis. The plans for this service
      are described.

PMID- 11824849
TI  - Self-perceived social integration and the use of day centers of persons with
      severe and persistent schizophrenia living in the community: a qualitative
      analysis.
AB  - BACKGROUND: The study examined how persons with severe and persistent
      schizophrenia perceive their social integration and how particular types of
      social integration are related to the use of day centers and patient clubs.
      METHODS: Problem-focused interviews on self-perceived social integration and the
      use of day structuring services were done with 100 persons with an ICD-9
      diagnosis of schizophrenia living in Leipzig. Transcribed interviews were
      subjected to computer-aided qualitative content analysis. RESULTS: Results of the
      qualitative content analysis show that the study participants can be classified
      in five different groups according to their self-perceived degree of social
      integration. The use and the subjective meaning of existing day structuring
      services was found to be associated with the type of self-perceived social
      integration. CONCLUSION: The heterogeneous ways persons with chronic
      schizophrenia organize their social lives lead to different kinds of needs for
      support. In order to meet the needs of the whole spectrum of patients this
      heterogeneity must be taken into account in the process of service planning.

PMID- 11824850
TI  - Lay recommendations on how to treat mental disorders.
AB  - BACKGROUND: Beliefs about the helpfulness of interventions are influencing the
      individual help-seeking behavior in case of mental illnesses. It is important to
      identify these beliefs as professional helpers are asked to consider them in
      their treatment recommendations. OBJECTIVE: Assessing lay proposals for an
      appropriate treatment of mental illnesses. METHODS: We conducted a representative
      opinion survey in Switzerland. Eighteen treatment proposals were presented with
      respect to a vignette either depicting schizophrenia or depression. Respondents
      were asked to indicate the proposals considered to be helpful for treatment and
      those considered to be harmful, respectively. RESULTS: 'Psychologist,' 'general
      practitioner,' 'fresh air, and 'psychiatrist' were mostly proposed as being
      helpful. Among several psychiatric treatment approaches 'psychotherapy' was
      favored, while psychopharmacological treatment and electroconvulsive therapy were
      only proposed by less than one-fourth of the interviewees. Especially
      psychotropic drugs were considered to be harmful. Treatment by a psychiatrist was
      regarded as being more helpful for schizophrenic individuals than for depressive
      persons. For a person experiencing a life crisis, treatment by a psychiatrist and
      psychological treatment were viewed as being harmful, and non-medical
      interventions were preferred. However, for persons thought to be mentally ill,
      psychiatric and psychopharmacological treatments were recommended. CONCLUSION:
      Mental health professionals are regarded as being helpful although their
      treatment methods are seen as being less helpful. A clear distinction is made
      between lay proposals for depression and schizophrenia. However, the perception
      of whether a condition is considered to be an illness or a life crisis has
      significantly more influence on lay treatment proposals than the cited diagnosis
      in the vignette.

PMID- 11824851
TI  - Theoretical frameworks for understanding and investigating the therapeutic
      relationship in psychiatry.
AB  - BACKGROUND: Mental health care is delivered through a relationship between a
      clinician and a patient. Although this therapeutic relationship is of central
      importance for mental health care, it appears to be relatively neglected in
      psychiatric research. Empirical research has for the most part adopted concepts
      and methods developed in psychotherapy and general medical practice. Hence,
      unpacking the presuppositions that have informed research on the therapeutic
      relationship to date may be a useful first step in developing this field. METHOD:
      A review of the literature was carried out. RESULTS: Six central theories are
      identified as framing the definitions and methods on this topic: role theory,
      psychoanalysis, social constructionism, systems theory, social psychology and
      cognitive behaviourism. To date, role theory, psychoanalysis and systems theory
      appear to be the frameworks most often applied in research in this field. Each
      perspective offers a unique emphasis in the analysis of the therapeutic
      relationship, which is reflected in the empirical work from each perspective
      discussed herein. CONCLUSIONS: None of the theories identified have been fully
      specified and comprehensively investigated in psychiatric settings. However, more
      than one approach may be used for thinking about relationships, depending on the
      treatment situation. Further specification and testing of the theories in
      psychiatric practice--taking account of the specific context--is warranted to
      underpin more pragmatic research. A stronger link between fundamental
      psychological and sociological research and applied health care research would
      advance our understanding of which elements of positive therapeutic relationships
      are instrumental in improving patient outcome and ultimately contribute to
      improving mental health care.

PMID- 11824852
TI  - Al-Ain community psychiatric survey IV: socio-cultural changes (traditionality
      liberalism) and prevalence of psychiatric disorders.
AB  - BACKGROUND This study was set to explore the relationship between socio-cultural
      change and psychopathology. METHOD: A representative sample (n = 1,394) of Al-Ain
      adult population had their psychopathology assessed with the Composite
      International Diagnostic Interview and other self-reported questionnaires, while
      the socio-cultural change was assessed with the modified version of the Socio
      cultural Change Questionnaire (ScCQ). The reliability and construct validity of
      the modified ScCQ were assessed. The overall Tradition Index, attitudinal and
      behavioural indices of the sample were estimated. Association between socio
      cultural change and psychopathology was also evaluated. RESULT: The reliability
      of the modified ScCQ was found to be moderate (alpha Cronbach 0.66) and the
      hypothesis regarding its construct validity was confirmed. Mean traditional index
      was found to be 0.61 +/- 0.14.Young, highly educated, skilled, and female
      subjects were found to be significantly less conservative and their scores on
      traditional index deviated significantly from overall mean. Less traditional
      people were also found to have a significantly increased rate of ICD-10
      psychiatric disorder and higher scores on psychopathology measures especially
      among females. Although females showed significantly more modern attitude, there
      were no significant sex differences in the expressed behaviour as measured by the
      behavioural Tradition Index. CONCLUSION: The findings of this study suggest that
      the prevalence of psychiatric disorder varies significantly according to the
      extent to which subjects adhere to traditional values.

PMID- 11824853
TI  - Magnesium infusion improves endothelium-dependent vasodilation in the human
      forearm.
AB  - The effect of intra-arterial magnesium infusion on endothelium-dependent
      vasodilation (EDV) in the forearm was studied in nine young healthy students
      (four men and five women). The EDV was assessed as forearm blood flow (FBF),
      measured by venous occlusion plethysmography, during infusion of methacholine
      (MCh). Endothelium-independent vasodilation (EIDV) was defined as FBF during
      infusion of sodium nitroprusside (SNP). During magnesium infusion in the brachial
      artery, 0.066 mmol/min, the concentration of ionized magnesium in venous plasma
      in the infused arm increased by 114%, from 0.59 (SD 0.04) to 1.26 (0.34) mmol/L
      (P = .0002). The FBF at baseline (ie, before administration of MCh or SNP)
      increased from 3.5 (1.1) to 7.3 (3.4) mL/min/100 mL tissue during magnesium
      infusion (P = .002). During low-dose MCh administration (2 microg/min), FBF
      increased by 24%, from 15.4 (5.5) to 19.1 (6.8) mL/min/100 mL tissue (P = .04),
      and during high-dose MCh administration (4 microg/min) FBF increased by 18%, from
      20.3 (6.4) to 24.0 (7.2) mL/min/100 mL tissue (P = .04). The EIDV did not change
      significantly. Systemic blood pressure was not significantly altered by magnesium
      infusion. No change in FBF either at rest or during infusion of MCh or SNP was
      observed during the time-control protocol. In conclusion, this in vivo study
      showed that intraarterial magnesium infusion increased EDV in the infused human
      forearm, which is in accordance with findings in previous in vitro and animal
      experiments.

PMID- 11824854
TI  - Correlates of aortic stiffness in elderly individuals: a subgroup of the
      Cardiovascular Health Study.
AB  - BACKGROUND: Arterial stiffness has been associated with aging, hypertension, and
      diabetes; however, little data has been published examining risk factors
      associated with arterial stiffness in elderly individuals. METHODS: Longitudinal
      associations were made between aortic stiffness and risk factors measured
      approximately 4 years earlier. Aortic pulse wave velocity (PWV), an established
      index of arterial stiffness, was measured in 356 participants (53.4% women, 25.3%
      African American), aged 70 to 96 years, from the Pittsburgh site of the
      Cardiovascular Health Study during 1996 to 1998. RESULTS: Mean aortic pulse wave
      velocity (850 cm/sec, range 365 to 1863) did not differ by ethnicity or sex.
      Increased aortic stiffness was positively associated with higher systolic blood
      pressure (SBP), age, fasting and 2-h postload glucose, fasting and 2-h insulin,
      triglycerides, waist circumference, body mass index, truncal fat, decreased
      physical activity, heart rate, and common carotid artery wall thickness (P <
      .05). After controlling for age and SBP, the strongest predictors of aortic
      stiffness in men were heart rate (P = .001) and 2-h glucose (P = .063). In women,
      PWV was positively associated with heart rate (P = .018), use of antihypertensive
      medication (P = .035), waist circumference (P = .030), and triglycerides (P =
      .081), and was negatively associated with physical activity (P = .111). Results
      were similar when the analysis was repeated in nondiabetic individuals and in
      those free of clinical or subclinical cardiovascular disease in 1992 to 1993.
      CONCLUSIONS: In these elderly participants, aortic stiffness was positively
      associated with risk factors associated with the insulin resistance syndrome,
      increased common carotid intima-media thickness, heart rate, and decreased
      physical activity measured several years earlier.

PMID- 11824855
TI  - Heart rate dependency of pulse pressure amplification and arterial stiffness.
AB  - BACKGROUND: Pulse pressure and aortic pulse wave velocity, measures of arterial
      stiffness, are both important determinants of cardiovascular risk. However,
      assessment of peripheral pulse pressure does not always provide a reliable
      measure of changes in central pulse pressure or arterial stiffness. The aim of
      the present study was to assess the effect of acute changes in heart rate on
      arterial stiffness and on peripheral and central pulse pressure in healthy
      subjects. METHODS: Twenty subjects (age range, 20 to 72 years) were studied at
      cardiac catheterization. Pulse wave analysis was used to determine central
      pressure, augmentation index (AIx), a measure of systemic arterial stiffness, and
      aortic pulse wave velocity (PWV) during right atrial pacing (80 to 120
      beats/min). RESULTS: Pulse pressure amplification increased during pacing due to
      a reduction in central pressure augmentation. AIx was significantly and inversely
      related to heart rate (r = -0.70, P < .001) due to an alteration in the relative
      timing of the reflected pressure wave, rather than a reduction in arterial
      stiffness, as PWV did not change. CONCLUSIONS: These data suggest that peripheral
      pulse pressure does not provide an accurate assessment of changes in central
      hemodynamics in relation to changes in heart rate, and that aortic stiffness is
      not affected by acute changes in heart rate.

PMID- 11824856
TI  - Assessment of endothelial function of the renal vasculature in human subjects.
AB  - BACKGROUND: L-Arginine, the substrate of nitric oxide (NO) synthase, and N(G)
      monomethyl-L-arginine (L-NMMA), a competitive inhibitor of endothelial NO
      synthase, are used to analyze endothelial function of the renal vasculature.
      However, little is known about the appropriate dose of L-arginine to be used and
      the duration of action of L-arginine and L-NMMA. METHODS: Twenty-nine healthy
      male subjects (age, 27+/-1 years) were examined. In protocol 1 (N = 17), L
      arginine at low (100 mg/kg) and high dose (250 mg/kg), and high-dose L-arginine
      combined either with L-NMMA (total dose, 4.25 mg/kg; N = 9) or placebo (N = 8)
      were given. In protocol 2 (N = 12), L-NMMA was given before L-arginine infusion
      (100 mg/kg). Glomerular filtration rate (GFR) and renal plasma flow (RPF) were
      measured at rest and at the end of each infusion step. RESULTS: In protocol 1, L
      arginine dose dependently increased RPF and GFR (RPF: 599+/-19 v 630+/-18 v 690+/
      24 mL/min, P <.05; GFR: 111+/-3 v 115+/-3 v 121+/-3 mL/min, P <.01; for baseline,
      L-arginine 100 mg/kg and 250 mg/kg, respectively). However, these changes could
      not be antagonized by coinfusion of L-NMMA to L-arginine 250 mg/kg: RPF and GFR
      remained unchanged in both the placebo and the L-NMMA group. In protocol 2, L
      NMMA decreased RPF (492+/-18 v 567+/-27 mL/min, P <.01) and increased GFR (122+/
      4 v 118+/-3 mL/min, P <.05). These changes could only be partially reversed by
      subsequent infusion of L-arginine (RPF: 533+/-15 mL/min; GFR: 121+/-4 mL/min;
      both parameters P = NS v L-NMMA and v baseline). CONCLUSIONS: L-arginine at a
      dose of 100 mg/kg is sufficient to analyze endothelial function of the renal
      vasculature. The prolonged effect of L-NMMA and L-arginine must be taken into
      account in study protocols using both substances. Thus, stimulation and blockade
      of NO synthase cannot be examined in the same protocol.

PMID- 11824857
TI  - Amlodipine versus chlorthalidone versus placebo in the treatment of stage I
      isolated systolic hypertension.
AB  - The study was to compare the effects of amlodipine (calcium channel antagonist),
      chlorthalidone (diuretic), and placebo in adults more than 50 years of age with
      stage 1 isolated systolic hypertension (ISH). After a 4-week placebo run-in
      phase, 150 patients were randomly assigned in a double-blind fashion to treatment
      with 5 mg of amlodipine (n = 48), 15 mg of chlorthalidone (n = 50), or placebo (n
      = 52). Patients who failed to meet the systolic blood pressure (BP) reduction
      goal by week 4 had their dose increased to 10 mg of amlodipine or 30 mg of
      chlorthalidone, and maintained at this increased dose for 12 weeks. Results
      showed a mean reduction (mean +/- SD) in sitting systolic BP from baseline to the
      last treatment visit of -14.6+/-12.2 mm Hg (95% confidence interval [CI] -18.2, 
      11.0), -14.0+/-13.46 mm Hg (95% CI -17.8, -10.2), and -3.4+/-11.83 mm Hg (95% CI 
      6.7, -0.1) for the amlodipine, chlorthalidone, and the placebo treatment groups,
      respectively. Both active treatments showed significantly greater reductions than
      the placebo group (P < or = .001), but were not significantly different from each
      other. Sixty-seven percent of the amlodipine, 69% of the chlorthalidone, and 25%
      of the placebo-treated patients reached the protocol defined systolic BP goal (P
      = .001). Both active treatment groups showed a trend of better systolic BP
      response in older patients (> or =65 years). Secondary efficacy measures
      including pulse pressure, standing systolic, diastolic, and the 24-h ambulatory
      BP were also statistically significantly improved for both active treatments at
      the end of treatment, except for chlorthalidone in standing diastolic BP. Adverse
      events that occurred during the study were as expected and were well tolerated.
      The results of this study support the efficacy and safety of amlodipine and
      chlorthalidone for the treatment of stage 1 ISH during 20 weeks of treatment.

PMID- 11824858
TI  - Antihypertensive therapy and orthostatic hemodynamic responses in acute stroke.
AB  - BACKGROUND: It is not known whether antihypertensive medications affect
      orthostatic blood pressure (BP) regulation in the early period after stroke.
      Knowledge of this may have implications for clinical practice. METHODS: A total
      of 40 acute ischemic stroke patients (mild-to-moderate severity) taking
      antihypertensive drugs, and 40 patients with acute stroke of similar severity not
      receiving such drugs were studied. Blood pressure and heart rate were measured
      while supine, and then for 5 min while sitting up and for 5 min in the standing
      posture. This was performed < or =3 days poststroke (day 1) and 1 week after the
      first study (week 1). RESULTS: In both groups of patients on day 1 and week 1,
      there was no significant fall in mean arterial pressure and heart rate after
      sitting up and standing up. Logistic regression analysis showed that only cardiac
      dysfunction was associated with orthostatic hypotension on univariate analysis
      (odds ratio 4.0, P = .02) and multivariate analysis when age, hypertension,
      stroke severity, and treatment were included (odds ratio 3.5, P = .05). Use of
      antihypertensive therapy was not associated with orthostatic hypotension on
      univariate or multivariate analysis. CONCLUSIONS: Use of antihypertensive drugs
      in the early period poststroke is not detrimental to postural BP regulation.
      Antihypertensive therapy may therefore be used when indicated in acute stroke,
      without having to restrict early mobilization; but the results cannot be
      extrapolated to the postacute phase.

PMID- 11824859
TI  - Role of vasopressin in 24-hour blood pressure regulation in diabetic patients
      with autonomic neuropathy.
AB  - To evaluate the role of vasopressin (AVP) on blood pressure (BP) in diabetic
      patients with autonomic neuropathy (AN), 10 patients were studied on a fixed
      sodium and potassium diet. On days 4 and 7, a 24-h BP monitoring, as well as
      blood and urine samples for sodium, potassium, creatinine, and osmolality
      determinations were obtained for every 4-h period; either placebo or an AVP-V1
      antagonist (d(CH2)5Tyr(me)AVP; 0.5 mg; AVPi) were given iv at 1 PM. On placebo,
      systolic BP (SBP) showed a progressive elevation during the day, declining after
      12 PM (8 AM to 12 AM 122+/-9; 12 AM to 4 PM 125+/-11; 4 PM to 8 PM 134+/-14; 8 PM
      to 12 PM 136+/-14; 12 PM to 8 AM 131+/-17 mm Hg). On AVPi this rise in SBP was
      blunted: 8 AM to 12 AM 125+/-122; 12 AM to 4 PM 121+/-21; 4 PM to 8 PM 126+/-16;
      8 PM to 12 PM 129+/-14; 12 PM to 8 AM 124+/-12 mm Hg. Creatinine clearance and
      diureses were greater during the night, both with placebo and AVPi. Plasma
      osmolality did not change on either day, although serum sodium decreased after
      AVPi, reaching the lowest values at 4 PM to 8 PM period (137+/-4.7 v 131+/-3.8
      mEq/L; P < .05). With placebo, fractional excretion of sodium (FENa) increased
      from 0.43%+/-0.32% during 12 h of orthostasis to 0.92%+/-1.05% during 12 h of
      recumbency (P < .02). With AVPi, the FENa on orthostasis did not differ from that
      with placebo, although BP values were lower and did not increase with recumbency
      (0.58+/-0.57 v 0.73%+/-0.49%; NS). In conclusion, our results show that in
      diabetic patients with AN, vasopressin participates in BP control by stimulating
      vascular and renal V1 receptors, which results in vasoconstriction and sodium
      reabsorption.

PMID- 11824860
TI  - Plasma-renin response to isotonic volume contraction in young salt-sensitive
      normotensive men.
AB  - Salt-sensitive persons have lower plasma renin activity than salt-resistant
      persons and their plasma renin activity increases less with a low sodium diet or
      volume depletion, compared to salt-resistant individuals. However, the time
      course of the renin response to acute volume contraction has not been studied in
      humans. Therefore, we designed an acute study in salt-sensitive and salt
      resistant normotensive volunteers, in which we examined the renin response to
      isotonic volume contraction. Twenty-four previously characterized salt-resistant
      (n = 13) and salt-sensitive (n = 11) persons were placed on a high salt diet
      containing 280 mmol NaCl/day for 3 days. After an overnight stay, volume
      depletion (total, 300 mmol Na) was induced by furosemide infusion. Free water
      deficits were replaced by 5% isotonic glucose infusion. Blood was obtained for
      electrolytes, plasma renin activity, and plasma aldosterone concentration. Blood
      pressure (BP) and heart rate were monitored during the experiment. Intravascular
      volume depletion resulted in a progressive increase in plasma renin activity that
      was both steeper and higher in salt-resistant than in the salt-sensitive subjects
      (P < .001). There was a slight increase in BP in response to volume contraction
      in both groups. Although heart rate did not change in salt-sensitive persons, it
      increased significantly (P < .001) in the salt-resistant group. These findings
      point to an intrinsic difference in the regulation of renin release between salt
      sensitive and salt-resistant subjects that may account for the different BP
      responses to changes in dietary sodium intake.

PMID- 11824861
TI  - A comparative trial of controlled-onset, extended-release verapamil, enalapril,
      and losartan on blood pressure and heart rate changes.
AB  - BACKGROUND: The excess morning risk of myocardial infarction and stroke may be
      attributable to the rapid rise in blood pressure (BP) and heart rate in the hours
      after awakening. The aim of this randomized, double-blinded, placebo-controlled,
      multicenter study was to compare once-daily, controlled-onset, extended-release
      (COER-24) verapamil to enalapril and losartan on BP and heart rate during the
      postawakening morning phase as well as throughout the 24-h period. METHODS: A
      total of 406 patients were randomized to an 8-week forced-titration period with
      one of the following: 1) COER-24 verapamil 240 mg/day titrated to 360 mg/day; 2)
      enalapril 10 mg/day titrated to 20 mg/day, 3) losartan 50 mg/day titrated to 100
      mg/day, or 4) placebo. Office BP and heart rate and ambulatory 24-h BP monitoring
      was performed at baseline, 4 weeks, and 8 weeks. RESULTS: Each active treatment,
      as compared with placebo, lowered BP both during the morning hours as well as the
      entire 24-h period. COER-24 verapamil was more effective in lowering morning
      systolic (-16.6 mm Hg) and diastolic (-11.9 mm Hg) BP than either enalapril or
      losartan (P < .001). For the entire 24-h period, the effects of COER-24 verapamil
      (-11.6/-8.4 mm Hg) were comparable to enalapril (- 13.4/-8.3 mm Hg; P = NS).
      Losartan achieved a similar 24-h effect on systolic pressure (-9.3 mm Hg) but was
      less effective on diastolic pressure (-5.4 mm Hg; P = .004 v COER-verapamil).
      Unlike losartan or enalapril, COER-24 verapamil was the only treatment to lower
      the heart rate over both the 24-h period (-4.6 beats/min; P < .001) and during
      waking hours (-4.6 beats/min; P < .001). A blunted rate of rise in BP, heart
      rate, and rate-pressure product occurred during the postawakening period with
      COER-verapamil (P = .03) but not with either of the other treatment arms. Lastly,
      the decline in BP at night was similar for COER-verapamil and losartan and
      greater with enalapril (P = .014) CONCLUSIONS: COER-24 verapamil produces changes
      in BP and pulse that more closely match the normal circadian hemodynamic rhythms
      than either do enalapril or losartan.

PMID- 11824862
TI  - Impaired saline-stimulated diuresis and natriuresis in the conscious hypertensive
      glucose-intolerant rat.
AB  - BACKGROUND: A major complication of type 2 diabetes is renal dysfunction, a
      condition that worsens with coexistence of systemic hypertension. However, less
      is known regarding the renal impact of the prediabetic condition characterized by
      glucose intolerance. Therefore, we tested the hypothesis that chronic glucose
      intolerance leads to abnormal renal function, a condition also exacerbated by
      concurrent systemic hypertension. METHODS: A rat model of concomitant NaCl
      sensitive hypertension and glucose intolerance was used to study renal function.
      Glucose intolerance was produced by administering streptozotocin to neonatal
      Wistar-Kyoto rats, and systemic hypertension was induced by combining dietary
      NaCl excess with unilateral nephrectomy. Hemodynamic and renal excretory
      responses were determined in conscious animals before and after administration of
      a 30-min isotonic saline challenge (5% of body weight, intravenously). RESULTS:
      Nine-month-old glucose-intolerant rats fed a normal NaCl diet did not manifest
      impairment in saline-stimulated diuresis and natriuresis. By contrast, 3-month
      old glucose-intolerant rats fed a high NaCl diet displayed an exaggerated
      diuretic and natriuretic response to a saline challenge. Although saline
      stimulated diuresis and natriuresis were enhanced in the hypertensive rats, they
      were reduced in the hypertensive glucose-intolerant animals. The reduction in
      renal excretory function of the latter group was caused by alterations in both
      glomerular function and tubular reabsorption of fluid and sodium. CONCLUSIONS:
      The coexistence of systemic hypertension and glucose intolerance result in
      impaired renal excretory function. This defect could be important, as
      hypertension can develop before the onset of overt type 2 diabetes.

PMID- 11824863
TI  - The renin-angiotensin and adrenergic nervous system in cardiac hypertrophy in
      fructose-fed rats.
AB  - BACKGROUND: Hyperinsulinemia and insulin resistance are associated with left
      ventricular hypertrophy (LVH) and cardiovascular complications in hypertensive
      subjects. The aim of this study was to explore the mechanisms for LVH including
      activation of the renin-angiotensin system system (RAS) and the sympathetic
      nervous system and their activation by insulin using a rat model of
      hyperinsulinemia and insulin resistance. METHODS: Male Sprague-Dawley rats were
      fed a high-fructose or control diet. The fructose-fed rats (FFR) were divided
      into four subgroups that were administrated either vehicle or the following
      antihypertensive drugs (n = 6-8) for 4 weeks: 1) olmesartan, an angiotensin II
      type 1 (AT1) receptor antagonist; 2) bunazosin, an alpha1-receptor blocker; and
      3) hydralazine, a direct vasodilator. RESULTS: Fructose feeding induced
      significant increases in mean systolic blood pressure (BP) levels at 4 weeks
      (control, 117 v fructose, 131 mm Hg), left ventricular weight, and the sum of the
      insulin level in response to a glucose tolerance test (2 g/kg). Fructose feeding
      also increased urinary excretion of epinephrine and norepinephrine, the density
      of cardiac alpha1-adrenergic receptors, and the content of angiotensin II in the
      left ventricle. All antihypertensive drugs decreased systolic BP, but only the
      AT1 receptor antagonist attenuated the development of LVH in FFR. The AT1
      receptor antagonist did not affect glucose-mediated insulin responses, but did
      suppress urinary catecholamine excretion and cardiac alpha1-adrenergic receptor
      density. CONCLUSIONS: Left ventricular hypertrophy in FFR may be less dependent
      on systemic elevations of BP and more dependent on the RAS and the sympathetic
      nervous system. Use of an AT1 receptor antagonist might be the most beneficial
      way to prevent progression of LVH through direct effects on tissue RAS and the
      sympathetic nervous system in FFR. As these changes occur in a rat model with
      hyperinsulinemia, insulin may have a role in promoting LVH by activating the
      local RAS and sympathetic nervous system activity.

PMID- 11824864
TI  - Effects of L-arginine on blood pressure and metabolic changes in fructose
      hypertensive rats.
AB  - In the present study, we examined the effects of chronic L-arginine treatment on
      plasma insulin levels and systolic blood pressure (SBP) in fructose-fed (F) rats.
      Fructose feeding resulted in hyperinsulinemia and elevated blood pressure when
      compared with that in controls (plasma insulin, 311.3+/-11.4 v control 164.4+/
      11.8 pmol/L, P < .05; SBP, 135.4+/-4.2 v control 105.5+/-1.3 mm Hg, P < .05). L
      arginine treatment of fructose-hypertensive rats prevented the development of
      hyperinsulinemia and hypertension (plasma insulin, 200.1+/-7.5 pmol/L; P < .05
      compared with that in F rats; SBP, 108.0+/-0.9 mm Hg; P < .05 compared with F
      rats). However, treatment with L-arginine did not influence any of these
      parameters in control rats. Statistical analysis of the data of plasma insulin
      level and SBP, revealed a significant correlation between these two variables. On
      the other hand, L-arginine treatment of F rats prevented the increased glucose
      and insulin concentrations in response to oral glucose challenge. L-arginine
      treatment also prevented the decrease in insulin sensitivity of F rats. These
      results indicate that L-arginine treatment is able to prevent fructose-induced
      hypertension and hyperinsulinemia. Our data also suggest a strong relationship
      between hyperinsulinemia and hypertension in this hypertensive rat model.
      Therefore, the antihypertensive effect of L-arginine could be, at least in part,
      the result of the restoration of plasma insulin levels by its vasodilator ability
      to increase blood flow to insulin sensitive tissues.

PMID- 11824866
TI  - Role of central angiotensin II receptors in cold-induced hypertension.
AB  - BACKGROUND: Earlier studies from this laboratory showed that central angiotensin
      II (AngII) receptors are upregulated by chronic cold exposure. The purpose of
      this study was to determine whether central AngII receptors may play a role in
      the development of cold-induced hypertension. METHODS: Four groups of rats (six
      rats each) were used. Two groups were exposed to cold (5 degrees C) and the other
      two groups were kept at 25 degrees C. One cold-exposed and one warm-adapted group
      were treated chronically, via osmotic minipumps, with AngII type 1 (AT1) receptor
      blocker (losartan, 6.0 microg/2.5 microL/h, intracerebroventricularly) at the
      beginning of cold exposure. RESULTS: Systolic blood pressure (BP) of the cold
      exposed untreated group increased during week 1 of cold exposure and rose to
      160+/-4 mm Hg by week 4, whereas BP of the losartan-treated group in cold did not
      increase and remained at 121+/-3 mm Hg. Cold-induced increases in drinking
      response to AngII, plasma renin activity, and urine norepinephrine output
      disappeared in the treated rats, indicating blockade of central AngII receptors.
      Withdrawal of losartan at 4 weeks resulted in an increase in BP of this group to
      the cold-exposed untreated level, which was accompanied by an increase in the
      above parameters. Significant increases in AngII-induced drinking response and
      hypothalamic AT1 receptor mRNA content of the cold-exposed rats indicate
      upregulation of AngII receptors during chronic cold exposure. Hypothalamic AngII
      level was not affected by cold exposure. CONCLUSION: Upregulation of brain AT1
      receptors plays a role in the development of cold-induced hypertension.

PMID- 11824867
TI  - How to use home blood pressure monitors in clinical practice.

PMID- 11824865
TI  - Chronic treatment with a superoxide dismutase mimetic prevents vascular
      remodeling and progression of hypertension in salt-loaded stroke-prone
      spontaneously hypertensive rats.
AB  - Oxidative stress has been implicated in the pathogenesis of hypertension. The aim
      of the present study was to determine whether increased generation of vascular
      superoxide anion (*O2-) contributes to blood pressure elevation by influencing
      vascular function and structure in severely hypertensive rats. Sixteen-week-old
      stroke-prone spontaneously hypertensive rats (SHRSP) (n = 12) were randomly
      divided into two groups to receive the superoxide dismutase mimetic, tempol (4
      hydroxy-2,2,6,6-tetramethyl piperidinoxyl) (1 mmol/L in drinking water) or tap
      water. Both groups were fed a high-salt diet (4% NaCl). Systolic blood pressure
      (SBP) was measured weekly for 6 weeks by the tail-cuff method. Rats were killed,
      and vascular structure (media:lumen ratio) and endothelial function
      (acetylcholine [Ach]-induced vasodilation) were assessed in small mesenteric
      arteries mounted as pressurized preparations. Vascular *O2- concentration was
      measured by lucigenin (5 micromol/L) chemiluminescence. Plasma total antioxidant
      status was assessed spectrophotometrically. The SBP increased significantly (P <
      .01) in the control group, whereas progression of hypertension was prevented in
      the tempol-treated group. Tempol reduced (P < .01) the media:lumen ratio (7.2%+/
      0.01%) compared with that in controls (12.0%+/-0.01%). Maximal Ach-induced
      dilation was altered in control rats (40%+/-9%) but was not influenced by tempol
      (57%+/-17%). Vascular *O2- concentration was lower (P < .01) and plasma total
      antioxidant concentration was higher (P < .05) in the treated group compared with
      the control. In conclusion, tempol prevents progression of hypertension. These
      processes are associated with attenuated vascular remodeling, decreased vascular
      *O2- concentration, and increased antioxidant status. Our data suggest that
      oxidative stress plays an important role in vascular damage associated with
      severe hypertension in salt-loaded SHRSP.

PMID- 11824868
TI  - Hypertension therapeutic research: a plea for change in the new millennium.

PMID- 11824869
TI  - New onset severe hypertension in an asymptomatic 6-year-old girl.

PMID- 11824870
TI  - Are there meaningful differences in blood pressure control with current
      antihypertensive agents?
AB  - Hypertension is a major risk factor for cardiovascular disease, and small
      reductions in blood pressure can have a substantial impact on outcome. Effective
      control of hypertension per se is important in reducing morbidity and mortality,
      but there is growing evidence that the class of drug used in treatment may affect
      patient outcomes. The Heart Outcomes Prevention Evaluation (HOPE) trial provided
      evidence that angiotensin converting enzyme inhibitors (ACEI), agents that
      inhibit the renin-angiotensin system (RAS), are particularly effective in
      reducing the risk of cardiovascular events in a wide range of patients. These
      beneficial effects of ACEI may be independent of antihypertensive effect.
      Angiotensin receptor blockers (ARB) are the newest class of antihypertensive drug
      to enter clinical use. By blocking the angiotensin II type 1 receptor, ARB
      achieve more complete blockade of the RAS than ACEI. The ARB also have a
      substantially better side effect profile than ACEI, and early evidence suggests
      that ARB are beneficial in combating hypertension-related target organ damage.
      These favorable characteristics suggest that ARB should be considered as first
      line treatment for hypertension. Based on comparative antihypertensive efficacy,
      olmesartan, a new ARB, may represent a significant addition to this drug class.

PMID- 11824871
TI  - Introduction: the hemodynamic and vascular effects of angiotensin II: managing
      the consequences.

PMID- 11824872
TI  - Clinical trials of angiotensin receptor blockers in heart failure: what do we
      know and what will we learn?
AB  - Although interruption of the renin-angiotensin system with angiotensin converting
      enzyme (ACE) inhibitors has evolved as the therapy of choice in heart failure
      based on large-scale morbidity and mortality clinical studies, treatment with
      angiotensin type 1 receptor blockers (ARB) offers an alternative and potentially
      superior method of treating this condition. Early pilot studies were quite
      promising; however, two well designed, large-scale trials have shown that the
      reduction in heart failure mortality with ARB is not significantly different from
      the reduction with ACE inhibitors. Possible reasons for lack of ARB superiority
      include insufficient dosing of ARB, differences in effects mediated through
      angiotensin II type 2 receptors, interaction with beta-blockers, and bradykinin
      mediated effects specific to ACE inhibitors. The ACE inhibitors remain the
      current therapy of choice in treating heart failure until further outcomes trial
      data become available; however, ARB are a reasonable alternative in patients
      intolerant of ACE inhibitors.

PMID- 11824873
TI  - Angiotensin and vascular fibrinolytic balance.
AB  - Fibrinolysis is controlled by the plasminogen activator system. The proteolytic
      activity of this system is mediated by plasmin, which is generated from
      plasminogen by one of two plasminogen activators. Plasminogen activator inhibitor
      1 (PAI-1) inhibits this process. Individuals with reduced fibrinolytic activity
      are at increased risk for ischemic cardiovascular events, and reduced
      fibrinolysis may underlie some of the pathological consequences of reduced nitric
      oxide (NO) availability. Within the vasculature, angiotensin II stimulates the
      release of PAI-1, thereby reducing fibrinolytic activity. Thus, the plasminogen
      activator system is largely controlled by the renin-angiotensin system (RAS). In
      accordance with this finding, treatment with angiotensin converting enzyme (ACE)
      inhibitors is associated with substantial reductions in the incidence of ischemic
      cardiovascular events. Links between the RAS, fibrinolytic balance, and
      cardiovascular pathology are further supported by evidence from transgenic and
      knockout animal models. This article discusses the role of the plasminogen
      activator system in cardiovascular pathology, and the potential for alleviating
      that pathology by manipulation of the RAS.

PMID- 11824874
TI  - Use of angiotensin II receptor blockers in animal models of atherosclerosis.
AB  - Long considered independent risk factors for end-stage vascular disease,
      hypertension and atherosclerosis may be intimately linked through their effects
      on vascular endothelial dysfunction, which are mediated by the renin-angiotensin
      system (RAS). Angiotensin II, a potent vasoconstrictor and the principal active
      peptide of the RAS, can also produce structural changes in the vessel wall
      associated with atherosclerosis. The role of RAS in the pathogenesis of
      atherosclerosis is supported by several lines of evidence, including the presence
      and upregulation of angiotensin-converting enzyme (ACE) and angiotensin II in the
      walls of atherosclerotic arteries. This article reviews recent research showing
      that administration of the angiotensin II type 1-receptor blocking agents (ARB)
      losartan and olmesartan medoxomil to cynomolgus monkeys with diet-induced
      hyperlipidemia prevents the progression of atherosclerosis. Since these effects
      have been achieved without altering blood pressure or plasma cholesterol levels
      significantly, it is suggested that these novel effects of angiotensin II
      receptor blocker treatment may extend the therapeutic profile of this class of
      agents in the prevention of human vascular disease.

PMID- 11824875
TI  - Open access follow-up for lung cancer: patient and staff satisfaction.
AB  - The majority of patients with lung cancer have incurable disease from
      presentation and a survival measured in months. Treatments offered to these
      patients are aimed at the palliation of symptoms with either radiotherapy or
      chemotherapy, or with supportive measures. It has been traditional to offer
      regular outpatient follow-up after initial palliative treatment. Further
      treatment options, which may be limited, are usually reserved for the recurrence
      of troublesome symptoms. A pilot 'open access' lung cancer clinic has been set
      up. Rather than have regular follow-up at the hospital, patients who have
      completed initial palliative treatments are discharged to the community with
      follow-up by their general practitioner and Macmillan nurse. Review at the open
      access clinic can be arranged at short notice if requested by the patient,
      carers, general practitioner or Macmillan nurse. The outcomes and level of
      satisfaction of patients, their relatives and staff to this method of follow-up
      were found to be positive. Open access follow-up may be useful for many patients
      after the completion of initial palliative treatment.

PMID- 11824876
TI  - Treatment of oral cancer: the need for defined protocols and specialist centres.
      variations in the treatment of oral cancer.
AB  - The authors of this study aimed to identify treatment philosophies for oral
      cancer within the west of Scotland and to investigate any survival differences
      associated with the various treatment options by means of a retrospective review
      of case notes and cancer registry data. All patients with squamous cancer of the
      tongue or floor of the mouth were identified from the West of Scotland Cancer
      Registry for the period 1984-1990. A total of 206 patients were available for
      study. Five different treatment protocols were identified: 5% of patients
      underwent biopsy only, 16% biopsy plus radiotherapy, 11% excisional biopsy, 25%
      radical surgery, and 42% radical surgery plus radiotherapy. Tumour staging by the
      TNM classification was an important factor that determined outcome. When
      adjusting for T stage and nodal involvement, there was a significant effect of
      treatment protocol on both the disease-free period (P < 0.001) and on survival (P
      < 0.001). The treatment options were used differently by individual clinicians
      and were related to stage of the disease. One hundred and forty-four (70%) of the
      patients were treated by a single combined head and neck unit based within the
      plastic surgery unit at Canniesburn Hospital. The remaining 62 were treated in 13
      different units throughout the west of Scotland. For those not treated in the
      combined head and neck unit, the increased hazard for recurrence was 1.43 (95%
      confidence interval (CI) 1.01-2.02), and the increased hazard ratio for death was
      1.48 (95% CI 1.06-2.06) when adjusting for tumour stage, and nodal involvement.
      Treatment philosophies for oral cancer have a significant effect on outcome.
      There is a need to develop clearly defined protocols based on staging and site of
      disease. We believe that treatment should be carried out within a
      multidisciplinary setting in a combined head and neck cancer unit.

PMID- 11824877
TI  - Daily general anaesthesia for radiotherapy in unco-operative patients:
      ingredients for successful management.
AB  - An unco-operative patient requiring daily radiation therapy presents a difficult
      clinical problem. After reviewing the paediatric oncology literature addressing
      the use of general anaesthesia for short medical procedures, we have developed
      checklists of procedural guidelines and monitoring equipment for the safe use of
      daily anaesthesia in adult patients who require a fractionated course of
      radiation therapy. We illustrate this by describing the successful treatment of a
      woman with autism and Hodgkin's disease who required daily general anaesthesia
      for immobilization during a 4-week course of radiation therapy. Propofol was used
      as the primary drug and was not associated with any adverse side-effects. There
      was no development of tolerance.

PMID- 11824878
TI  - The development of a protocol for the use of 5-HT3 antagonists in chemotherapy
      induced nausea and vomiting.
AB  - The purpose of this study was to evaluate the effectiveness of three 5-HT3
      antagonists in routine clinical practice. The ultimate aim was to develop an
      antiemetic protocol, selecting a single 5-HT3 antagonist. Each of the drugs was
      studied for a 4-month period and data was collected from patients on nausea,
      vomiting (both acute and delayed) and side-effects by means of a diary card. A
      total of 274 patients were enrolled into the study. Success rates for acute
      emesis seen over the study period were in excess of 90%. There were no
      statistically significant differences between any of the three drugs investigated
      with respect to both acute and delayed nausea and vomiting. Similarly, there was
      no difference between the three groups for the incidence of constipation,
      diarrhoea and headache. Granisetron demonstrated a lesser deviation from the
      protocol in respect of the number of intravenous doses given to patients. The
      study allowed an effective 5-HT3 antagonist protocol to be developed for use in
      the management of nausea and vomiting in cancer patients.

PMID- 11824879
TI  - Trastuzumab: designer drug or fashionable fad?
AB  - Trastuzumab (Herceptin) is the first monoclonal antibody to be approved for the
      treatment of a solid tumour and is directed against the c-erb-B2 receptor. c-erb
      B2 is a member of the epidermal growth factor family and approximately 25% of
      breast cancers express such receptors, which appear to confer a poorer prognosis
      and may be an indicator of resistance to cytotoxic chemotherapy. This review
      assesses the mechanisms of action of trastuzumab, discusses the measurement of
      the HER-2/neu gene and its products, and describes the preclinical and clinical
      studies that have been instrumental to date in the emergence of trastuzumab in
      clinical practice.

PMID- 11824880
TI  - Use of capecitabine as first-line therapy in patients with metastatic breast
      cancer relapsing after high-dose chemotherapy and autologous stem cell support.
AB  - High-dose chemotherapy with autologous stem cell support (HDC-ASCS) can produce
      high complete remission rates in patients with metastatic breast cancer (MBC).
      However, the majority of those so treated will relapse within 3 years. The
      ability of such patients to tolerate further myelosuppressive chemotherapy may be
      limited and the best therapy is undefined. In this retrospective study we
      assessed the role of capecitabine as initial therapy after relapse. Ten patients
      (median age = 47 years; oestrogen receptor-positive, n = 4; visceral disease, n =
      6; prior anthracycline, n = 8, prior taxanes, n = 10), whose disease progressed
      at a median of 246 days (range 69-480) after HDC-ASCS and who were treated with
      capecitabine (2500 mg/m2 per day for 2 weeks of a 3-week cycle) as initial
      therapy for relapse, were assessed retrospectively for response and toxicity.
      They received a median of eight cycles (range 4-24) of capecitabine. The
      toxicities encountered while receiving capecitabine were: hand-foot syndrome
      (grade 1, n = 3; grade 2, n = 4; grade 3, n = 1); diarrhoea (grade 1, n = 1;
      grade 2, n = 3); nausea (n = 2) and fatigue (n = 5). Haematological toxicity was
      seen in only one patient. No patient required hospitalization for toxicity. Three
      achieved a complete remission, four a partial remission and three disease
      stabilization. After a median follow-up of 183 days from commencing capecitabine
      (range 97-540), all patients were alive and five were in remission. Five
      progressed after remissions that lasted between 63 and 252 days. Oral
      capecitabine is an active and well-tolerated agent when used alone as first-line
      therapy in patients who have relapsed after HDC-ASCS for MBC.

PMID- 11824881
TI  - Lacrimal duct stenosis and other ocular toxicity associated with adjuvant
      cyclophosphamide, methotrexate and 5-fluorouracil combination chemotherapy for
      early stage breast cancer.
AB  - Certain side-effects of chemotherapy are well recognized but ocular toxicity is
      often underestimated. This retrospective study was undertaken after we became
      aware of a case of irreversible lacrimal duct stenosis in a woman receiving
      adjuvant chemotherapy for early stage breast cancer. Using the chemotherapy
      records, 128 patients who received adjuvant cyclophosphamide, methotrexate and 5
      fluorouracil combination chemotherapy for early stage breast cancer over a 2 1/2
      year period were identified. The case notes of these patients were reviewed and
      an 18% incidence of ocular side-effects, including four other cases of epiphora,
      was identified. The epiphora resolved fully on completion of chemotherapy in
      these four patients but not in the index patient. The optimal management of these
      side-effects is unclear but it needs to be tailored to the particular toxicity
      experienced by the patient.

PMID- 11824882
TI  - Acute abdomen during adjuvant chemotherapy: superior mesenteric artery thrombosis
      associated with CMF chemotherapy.
AB  - We report a case of superior mesenteric artery thrombosis in a 57-year-old woman
      undergoing chemotherapy for T1N1M0, breast cancer. Although cancer itself is
      associated with an increased risk of thrombotic events, treatment with
      chemotherapy and/or tamoxifen in breast cancer patients increases this risk. Most
      cases reported are of venous thromboembolism; arterial events are rare.

PMID- 11824883
TI  - Current trends in colorectal cancer: what they tell us and what we still do not
      know.

PMID- 11824884
TI  - Current trends in colorectal cancer: site, incidence, mortality and survival in
      England and Wales.
AB  - The objective was to examine trends in colorectal cancer (CRC) incidence and
      mortality in England and Wales over the last 30 years. Age-standardized
      incidence, mortality and survival rates for CRC, based on data from the National
      Cancer Intelligence Centre at the Office for National Statistics, were calculated
      and trends assessed. Between 1971 and 1997 the total number of cases of CRC
      increased by 42%, from 20,400 to 28,900. The site distribution of CRC between
      1971 and 1994 was: rectum 38%, sigmoid 29%, caecum 15%, transverse colon and
      flexures 10%, ascending colon 5%, and descending colon 3%. Between 1971 and 1997
      the direct age-standardized incidence increased by 20% in males and by 5% in
      females. The direct age-standardized mortality fell by 24% in males and by 37% in
      females. Age-standardized relative 5-year survival in adults improved from 22%
      27% for patients diagnosed during 1971-1975 to over 40% for those diagnosed
      during the period 1991-1993. In conclusion, the incidence of CRC in England and
      Wales has been steadily rising. It is more common in males and has increased more
      rapidly in males than in females. The reasons for these trends remain unclear.
      Five-year survival has improved substantially, but rates are still below those in
      comparable countries elsewhere in Europe and in the USA.

PMID- 11824885
TI  - Chemotherapy for prostate cancer.

PMID- 11824886
TI  - First report of an isolated jejunal seminoma: presentation with melaena and iron
      deficiency anaemia.
AB  - We present the case history of a man with isolated seminoma in the jejunum and
      abnormal testes but no provable malignant testicular disease. Treatment with
      cisplatin-based chemotherapy led to complete resolution of the jejunal seminoma.
      The rarity of seminoma involving the small bowel is highlighted. A literature
      search did not reveal other similar cases of isolated seminoma affecting the
      jejunum. The possible origins of this tumour are discussed.

PMID- 11824887
TI  - Prospective randomized comparison of dacarbazine (DTIC) versus DTIC plus
      interferon-alpha (IFN-alpha) in metastatic melanoma.
AB  - Dacarbazine (DTIC) has been the mainstay of chemotherapy for metastatic melanoma
      for over two decades, but only 15%-20% of patients respond and benefit is usually
      transient. Randomized studies combining DTIC with interferon-alpha (IFN-alpha) in
      advanced disease have so far been inconclusive in terms of response and survival.
      We report a randomized prospective pilot Phase III trial of DTIC +IFN-alpha in
      patients with metastatic melanoma. The primary endpoint was death. A total of 61
      patients were randomized between April 1995 and April 1998. Differences in
      survival between groups were assessed using log-rank analysis. Quality of life
      was measured using the European Organization for Research on Treatment of Cancer
      QLQ C30 (+3) questionnaire. Fifty-seven patients died during the study. The
      median survival for patients receiving DTIC was 7.2 months (95% confidence
      interval (CI) 4.4-9.0); it was 4.8 months for DTIC + IFN-alpha (95% CI 2.0-8.0).
      There was no significant difference in survival between the two treatment arms
      (chi2 unadjusted = 0.15, P = 0.70; chi2 adjusted = 0.01, P = 0.91). The 6-month
      survival of those patients randomized to DTIC alone was 58% compared with 40% for
      those patients randomized to DTIC + IFN-alpha. There were no differences in
      quality of life between treatment groups. This study failed to demonstrate a
      survival benefit for patients receiving IFN-alpha in combination with DTIC. These
      results are inconclusive primarily owing to the small size of the trial. A meta
      analysis is required to determine whether there is a role for the addition of IFN
      alpha to DTIC in the treatment of this disease.

PMID- 11824888
TI  - Spontaneous regression of metastatic malignant melanoma of the parotid gland and
      neck lymph nodes: a case report and a review of the literature.
AB  - We report the case history of a patient with complete spontaneous regression of
      metastatic cutaneous melanoma with parotid and neck lymph node metastases.
      Complete spontaneous regression of metastatic melanoma is very rare, with an
      estimated incidence of 0.22%-0.27%. We review the literature on this subject.
      Elucidation of the process of spontaneous regression may offer the possibility of
      improved methods of treating and preventing cancer.

PMID- 11824889
TI  - Radiation recall dermatitis in a patient treated with dacarbazine.
AB  - Radiation recall describes an inflammatory reaction at a previously irradiated
      site associated with the use of chemotherapeutic agents. Dacarbazine, a tetrazine
      cytotoxic drug, has not been noted to cause this phenomenon. We report the case
      history of a 44-year-old female patient who developed a recall dermatitis due to
      dacarbazine in a site previously irradiated for the treatment of malignant
      melanoma. The skin erythema responded quickly to oral corticosteroid treatment.
      Further cycles of dacarbazine were facilitated with oral corticosteroid
      premedication. We conclude that dacarbazine should be considered as a potential
      cause of radiation recall dermatitis and that this can be managed and prevented
      with oral corticosteroids.

PMID- 11824890
TI  - Is screening for cervical cancer effective?

PMID- 11824891
TI  - Anti-Yo antibody-positive cerebellar degeneration associated with endometrial
      carcinoma: case report and review of the literature.
AB  - Paraneoplastic cerebellar degeneration (PCD) is a rare, severely debilitating
      disease, often with a rapid onset and progression, which predate the diagnosis of
      malignancy. Despite characteristic features, diagnosis is commonly difficult and
      successful therapy, which relies on early instigation of treatment, is rare. Here
      we present a patient in whom anti-Yo antibody-positive PCD was associated with
      endometrial carcinoma and an extensive review of the literature outlining the
      clinical features, pathogenesis and treatment of PCD.

PMID- 11824892
TI  - Chemotherapy in patients with advanced non-small cell lung cancer.

PMID- 11824893
TI  - Mitomycin C, vinblastine and carboplatin: effective outpatient chemotherapy for
      advanced non-small cell carcinoma of the lung (NSCLC).
AB  - The majority of patients diagnosed with non-small cell lung carcinoma (NSCLC)
      present with advanced disease and, as such, are treated with palliative intent.
      Platinum-based combination chemotherapy plays an important role in the management
      of these patients, with response rates to most regimens being in the range of 30%
      40%. with symptom relief in up to 60%. One of the most commonly utilized
      combinations is mitomycin C, vinblastine and cisplatin (MVP). Owing to the
      hydration regimen, and to the age and performance status of many of these
      patients, in reality this combination often necessitates an overnight stay in
      hospital. A combination of drugs that could be administered as an outpatient
      would be beneficial to patients and could result in substantial economic
      benefits. Forty-three patients with Stage IlIb and IV NSCLC were treated with the
      MVCarbo regimen, in which the cisplatin in the MVP regimen was replaced with
      carboplatin. All treatment was administered on an outpatient basis. The overall
      objective response rate was 30%; the symptomatic response rate was 60%, which was
      exactly equivalent to the response rate seen in a comparable group of patients
      treated with MVP in a trial on duration of chemotherapy at the Royal Marsden
      Hospital. There was no difference in progression-free or overall survival between
      patients treated with the two regimens. The MVCarbo regimen resulted in response
      rates and survival rates equivalent to those seen with standard MVP and, as such,
      provides an acceptable outpatient alternative to this treatment.

PMID- 11824894
TI  - Prostate cancer treated with brachytherapy in a group of patients who previously
      underwent pelvic radiotherapy for testicular cancer.

PMID- 11824895
TI  - Social and environmental factors influence the suppression of pup-directed
      aggression and development of paternal behavior in captive meadow voles (Microtus
      pennsylvanicus).
AB  - During summer, female meadow voles (Microtus pennsylvanicus) maintain territories
      and males do not engage in paternal care. As day length shortens, territories
      dissolve and males nest with females and young. Because paternal behavior has
      never been studied in free-living meadow voles during colder months or in the
      laboratory under short photoperiods, the authors examined whether males housed in
      short day (SD) lengths exhibited more frequent or better quality paternal
      behavior than males housed in long day (LD) lengths. Sexually and parentally
      inexperienced (naive) SD males exhibited proportionally more and qualitatively
      better paternal care than naive LD males. SD males were more responsive than LD
      males to classic social cues associated with prepartum aggression inhibition and
      paternal onset. SD sires also displayed qualitatively better paternal behavior
      than LD sires. These data suggest that meadow vole paternal state is regulated by
      specific social and environmental cues that may contain reliable information
      about ecological conditions that favor paternal care.

PMID- 11824897
TI  - How tree shrews (Tupaia belangeri) perform in a searching task: evidence for
      strategy use.
AB  - This study investigated how male tree shrews (Tupaia belangen) performed in a
      searching task while in their home cages and assessed whether different food
      distributions affected their performance. The animals were faced with a holeboard
      containing 9 food sources arranged in a 3 x 3 matrix or in 3 clusters, each
      containing 3 sources. Animals tended to start and end the trials from preferred
      locations, thereafter solving the task by strategically organizing the reward
      collection according to a minimum-distance principle. In the cluster
      configuration, they visited the sources hierarchically. Food distribution did not
      affect the performance. Comparison with data from mice and capuchin monkeys
      revealed that tree shrews and capuchins solved the task in a similar strategic
      way, whereas mice did not. These findings attract particular attention because of
      the phylogenetic position of tree shrews, which are regarded as closely related
      to primates.

PMID- 11824896
TI  - Differential use of vocal and gestural communication by chimpanzees (Pan
      troglodytes) in response to the attentional status of a human (Homo sapiens).
AB  - This study examined the communicative behavior of 49 captive chimpanzees (Pan
      troglodytes), particularly their use of vocalizations, manual gestures, and other
      auditory- or tactile-based behaviors as a means of gaining an inattentive
      audience's attention. A human (Homo sapiens) experimenter held a banana while
      oriented either toward or away from the chimpanzee. The chimpanzees' behavior was
      recorded for 60 s. Chimpanzees emitted vocalizations faster and were more likely
      to produce vocalizations as their 1st communicative behavior when a human was
      oriented away from them. Chimpanzees used manual gestures more frequently and
      faster when the human was oriented toward them. These results replicate the
      findings of earlier studies on chimpanzee gestural communication and provide new
      information about the intentional and functional use of their vocalizations.

PMID- 11824898
TI  - Early temperamental traits in an octopus (Octopus bimaculoides).
AB  - During their 3rd week of life, 73 Octopus bimaculoides were observed to test
      whether discrete behaviors could be grouped reliably to reflect dimensions of
      temperament. Frequencies of behaviors during Week 3 were subjected to principal
      components analysis (PCA), resulting in 4 components (active engagement,
      arousal/readiness, aggression, and avoidance/disinterest) that explain 53% of the
      variance. Levels of temperamental traits were then evaluated for 37 octopuses
      using composite scores at 3 time points across the first 9 weeks of life. Profile
      analysis revealed significant change for the testing group as a whole in trait
      expression levels from Week 3 to Week 6. Results also suggest a significant
      effect of relatedness on developing temperamental profiles of octopuses.
      Discussion focuses on how results apply to the life history of O. bimaculoides
      and what temperament can reveal about adaptive individuality in a protostome.

PMID- 11824899
TI  - Hand preference for food processing in wild western lowland gorillas (Gorilla
      gorilla gorilla).
AB  - Western lowland gorillas (Gorilla gorilla gorilla) have not previously been
      represented in studies of laterality in wild great apes. The discovery of swampy
      clearings frequented by gorillas in northern Congo has provided the first
      opportunity to redress this imbalance. Hand preference data are presented from 33
      gorillas in seated and standing postures, covering the procurement and processing
      of 2 to 4 plant species. Levels of hand preference exhibited were low. When data
      from all postures and plant species were pooled, 33% of gorillas showed hand
      preferences in excess of chance. In the standing posture, more gorillas exhibited
      significant left-hand preferences than right, but an overall population-level
      bias was not evident.

PMID- 11824901
TI  - Spontaneous use of magnitude discrimination and ordination by the orangutan
      (Pongo pygmaeus).
AB  - The ability to discriminate quantity is descriptive of general cognitive ability.
      In this study, the authors presented 2 orangutans (Pongo pygmaeus) with a
      quantity judgment task. Each trial consisted of 2 choices, ranging from 1 to 6
      food items in each. The orangutan chose 1 of the quantities, which was removed,
      and the remaining array was given as a reward. In contrast to chimpanzees
      previously tested on the same task (S. T. Boysen & G. G. Berntson, 1995; S. T.
      Boysen, G. G. Berntson, M. B. Hannan, & J. T. Cacioppo, 1996; S. T. Boysen, K. L.
      Mukobi, & G. G. Berntson, 1999), the orangutans optimized their performance.
      Orangutans, therefore, attend to differences in magnitude and can spontaneously
      use ordinality. Results also suggest a cognitive difference between chimpanzees
      and orangutans.

PMID- 11824900
TI  - Simultaneous development of vocal and physical object combinations by a Grey
      parrot (Psittacus erithacus): bottle caps, lids, and labels.
AB  - On the basis of primarily behavioral data, researchers (e.g., P. M. Greenfield,
      1991) have argued (a) that parallel development of communicative and physical
      object (manual) combinatorial abilities exists in young children; (b) that these
      abilities initially have a common neural substrate; (c) that a homologous
      substrate in great apes allows for similar, if limited, parallel development of
      these 2 abilities; and (d) that such abilities thus may indicate a shared
      evolutionary history for both communicative and physical behavior (J. Johnson
      Pynn, D. M. Fragaszy, E. M. Hirsh, K. E. Brakke, & P. M. Greenfield, 1999). The
      authors of the present study found a comparable, if limited, parallel
      combinatorial development in a Grey parrot (Psittacus erithacus). Given the
      evolutionary distance between parrots and primates, the authors suggest that the
      search for and arguments concerning responsible substrates and common behavior
      should be approached with care and should not be restricted to the primate line.

PMID- 11824902
TI  - Relationship with the mother modulates the response of yearling Japanese macaques
      (Macaca fuscata) to the birth of a sibling.
AB  - The authors investigated the changes induced by the birth of a sibling in the
      relationship of 1-year-old Japanese macaques (Macaca fuscata) with their mothers
      and group companions. After the birth of a sibling, mother-yearling contact,
      proximity, and grooming decreased dramatically. Yearlings responded to such a
      reduction in maternal care in either of 2 radically different ways. Yearlings
      either sought attention from group companions and showed no sign of depression or
      did not compensate for the mother's reduced availability and became depressed.
      The modality of response was predicted by the quality of the relationship with
      the mother before the sibling birth. Yearlings that had spent a larger amount of
      time in contact with their mothers were less likely to become depressed. Security
      of the attachment relationship with the mother may be the factor mediating the
      link between the time in contact and the yearling's response to the birth of a
      sibling.

PMID- 11824903
TI  - Cognitive maps not used by humans (Homo sapiens) during a dynamic navigational
      task.
AB  - To account for the impressive navigational ability of animals, some researchers
      have suggested that animals might use a cognitive map. Two groups of human
      participants (Homo sapiens) were tested for cognitive mapping using procedures
      similar to those used by B. M. Gibson and A. C. Kamil (2001). Participants who
      had to acquire spatial information about a hidden goal from the experimental
      contingencies alone showed patterns of search most like nutcrackers in the
      companion study (B. M. Gibson & A. C. Kamil, 2001). Surprisingly,
      postexperimental questionnaires revealed that most participants used an
      alternative strategy of vector integration rather than cognitive mapping during
      search for the hidden goal. The current study and its companion indicate that
      some simpler mechanisms of navigation are flexible enough to account for what
      appears to be map-based behavior in human and nonhuman species.

PMID- 11824904
TI  - Tests for cognitive mapping in Clark's nutcrackers (Nucifraga columbiana).
AB  - In these experiments, the authors examined the nature of the spatial information
      that Clark's nutcrackers (Nucifraga columbiana) use during navigation and whether
      this information is represented in the form of a cognitive map. In Experiment 1,
      nutcrackers were able to use distal cues to locate a small hidden goal. In
      Experiments 2 and 3, nutcrackers were given the opportunity to develop a map of a
      room by viewing local subsets of the landmarks in the room at a goal during
      training. During transfer tests, nutcrackers were presented with a landmark
      panorama that was not previously seen at the goal. Of 3 nutcrackers that had
      learned the relationship between distal cues and the goal, 3 were able to locate
      the goal during transfer, indicating they may have developed a cognitive map.
      Experiments 4 and 5 suggest that the simpler mechanism of vector integration may
      have been used by some nutcrackers during the transfer tests.

PMID- 11824905
TI  - New methodology applied to bonnet macaques (Macaca radiata) to address some
      contradictory evidence on manual asymmetries in Old World monkeys.
AB  - Seven bonnet macaques (Macaca radiata) with strong hand preferences in performing
      a computer-generated joystick task that required directing a cursor to contact a
      small stationary target on a monitor were given comparable experience with each
      hand on the task over a 5-week period. Hand use was randomly restricted to either
      only the left or only the right hand across trials by automatically inputting
      into a computer the unique identification numbers of microchips implanted in the
      forearms of each macaque. Subsequent presentation of a novel task requiring
      maintenance of contact between a cursor and a moving target revealed no
      performance difference between preferred and nonpreferred hands or between left
      and right hands on the basis of number of errors or time to complete the task.
      The findings suggest that the strong hand preference for these tasks does not
      derive from a performance advantage for the preferred hand.

PMID- 11824906
TI  - Attachment behavior of adult dogs (Canis familiaris) living at rescue centers:
      forming new bonds.
AB  - In this study, 60 shelter dogs (Canis familiaris) were observed in the modified
      version of the Strange Situation Test, which has proved to be a useful method for
      studying dogs' attachment behavior toward humans (J. Topal, A. Miklosi, V.
      Csanyi, & A. Doka, 1998). Before testing, 40 dogs were handled 3 times for 10
      min. In the test, handled dogs encountered 2 persons: the handler in the role of
      the "owner" (OW) and an unfamiliar person (UP), whereas the 20 nonhandled dogs
      encountered unfamiliar persons in both roles. Dogs in the handled group exhibited
      more contact seeking with the entering OW, less physical contact with the UP,
      less frequent following of the leaving UP, and less standing by the door in the
      presence of the OW. The specific response of the handled dogs toward the handler
      fulfilled the operational criteria of attachment. In shelter conditions, the
      remarkable demand for social contact with humans may result in rather fast
      forming of attachment even in adult dogs.

PMID- 11824907
TI  - Tracking responses related to self-recognition: a frequency comparison of
      responses to mirrors, photographs, and videotapes by cotton top tamanins
      (Saguinus oedipus).
AB  - The frequency of responses cotton top tamarins (Saguinus oedipus) emitted
      indicative of self-recognition to a mirror was compared with the frequencies of
      responses emitted to digitized photographs of tamarins (Experiment 1) and to
      videotapes of real-time or prior tamarin action (Experiment 2). Results indicated
      more attentional responses toward the mirror in both studies, but behavioral
      indices of self-recognition were not consistently generated by the mirror. The 2
      experiments confirmed that real-time self-reflection is a condition that
      generates heightened attention and rare examples of particular mirror-specific
      behaviors in tamarins.

PMID- 11824908
TI  - A possible function of the preference for hind nipples in prairie voles (Microtus
      ochrogaster).
AB  - Prairie vole pups (Microtus ochrogaster) in laboratory cages prefer hind nipples.
      In this research, the author observed 8 litters of prairie voles in a seminatural
      environment to confirm the preference for hind nipples and to determine if young
      on hind nipples were groomed more frequently or dislodged less frequently than
      were young on other nipples. Prairie vole pups in seminatural environments
      preferred hind nipples; this preference was illustrated by the progressive use of
      more anterior nipples only as litter size increased and by the reluctance of pups
      to voluntarily release their hold on hind nipples. Maternal grooming of young did
      not vary with suckling location. Prairie vole young on hind nipples, however,
      were dislodged less frequently than were young on other nipples. Less frequent
      dislodgment from hind nipples during maternal movements may play a role in the
      preference for hind nipples in prairie voles.

PMID- 11824909
TI  - Oman Family Health Survey 1995.
AB  - Rapid improvements have been occurring in public health and in individual health
      status in the Sultanate of Oman as a result of the 5-year health development
      plans that have been implemented since 1976, and also because of accelerated
      socioeconomic progress. A nationwide health survey was conducted in 1995 as part
      of the Gulf Family Health Project of the Council of Health Ministers of GCC
      States. This paper describes the survey methodology used and the results. In the
      process of rapid epidemiologic transition currently occurring in the country the
      survey results provide a perspective of public health in the Sultanate of Oman.

PMID- 11824910
TI  - HIV risk environment for Ghanaian women: challenges to prevention.
AB  - Ghana is experiencing high rates of HIV transmission and women have been
      identified as a group with increased vulnerability to infection. Women's
      vulnerability may be influenced by factors such as gender, unequal power
      relationships and poverty. Research was undertaken in Ghana from January to May
      1999 to examine the experiences of HIV sero-positive women. Thirty-one women were
      interviewed to explore the broad context of disease transmission and to identify
      factors that mediated women's ability to protect themselves from infection. The
      poverty experienced by many of the women during their childhood years, coupled
      with a societal belief that favored the education of males, restricted the
      participants' educational and vocational opportunities. With limited education
      and few vocational skills, many of the women took boyfriends to assist them with
      the purchase of food, clothing and shelter, as a strategy for survival. For most
      women, the use of condoms with sexual partners was restricted by the high value
      placed on fertility, the negative association of condoms with prostitution, and
      the women's limited ability to influence decision-making in this area. The
      women's narratives provide a compelling description of the context of HIV
      transmission in Ghana. Strategies to expand and intensify the response to HIV
      prevention are presented and critiqued.

PMID- 11824911
TI  - Is nondirectiveness possible within the context of antenatal screening and
      testing?
AB  - Partly in order to dissociate itself from eugenics, genetic counselling values
      the principle of nondirectiveness as a key feature. Recent reports have upheld
      the importance of this approach, treating it unproblematically. However, doubts
      have been expressed about whether nondirective counselling is possible or indeed,
      desirable. Changes in organisational aspects of antenatal screening delivery in
      the UK have meant that genetic counselling is now being carried out by a variety
      of practitioners other than counsellors and specialists. These are often
      practitioners such as obstetricians and midwives who, in many other aspects of
      their work do not practise in a nondirective way. This paper explores some of the
      difficulties health practitioners encountered when attempting to work
      nondirectively. Reasons given by practitioners for not following this approach
      fell into categories, which in turn formed a continuum. Categories along the
      continuum ranged from acting directively at the request of women, through to
      deciding for women, either covertly or overtly, in their "best interests". It
      appears that for practitioners, the boundary between choice and coercion is not a
      clearcut one, and visualising it instead as a continuum may make it easier to see
      how slippage between choice and coercion can occur. The paper highlights the
      dilemmas which a variety of practitioners are dealing with in their daily work,
      in the hope of encouraging debate about these complex clinical and ethical
      issues.

PMID- 11824912
TI  - 'The thief of womanhood': women's experience of polycystic ovarian syndrome.
AB  - Previous research on polycystic ovarian syndrome (PCOS) has overwhelmingly been
      conducted within a medical or psychiatric framework, and has failed to explore
      women's own experience of the syndrome. Interviews were conducted with 30 women
      with PCOS recruited through a national self-help organisation. Thematic analysis
      of the interviews revealed pervasive reports of feeling 'freakish', 'abnormal',
      and not 'proper' women. These feelings were related to three symptoms commonly
      experienced by women with PCOS: 'excess' hair growth; irregular, absent or
      disrupted periods; and infertility. Smooth hairless bodies and faces, regular
      menstruation and the capacity to bear children were associated with femininity,
      and as a result of their symptoms women expressed feeling 'different' from other
      women and less 'feminine'. The results are discussed within a feminist framework
      and suggest that polycystic ovarian syndrome is a deeply stigmatising condition,
      'a theft of womanhood', with far reaching implications for all women, whether or
      not they conform to 'feminine' norms.

PMID- 11824913
TI  - Physiognomy, familism and consumerism: preferences among Jewish-Israeli
      recipients of donor insemination.
AB  - This paper examines the physiological preferences of Jewish-Israeli donor
      insemination (DI) recipients regarding the desirable donor. (1) By comparing
      recipients' own physiognomy with that of a hypothetical donor, we explore some of
      the social potentials of DI in its emerging democratized form. We examine
      prevailing notions regarding the 'natural family' and 'family resemblance' and
      query the relative weight of the natural vs. the consumer model as applied to
      one's own family through considerations regarding physical appearance. While
      examining the 'natural family' concept as a limit in the making of actual Israeli
      families, we consider the meanings of choice in the context of procreative
      technologies. The study may also provide practitioners with relevant information
      for donor matching. The paper is based on questionnaires delivered in four sperm
      banks during the years 1995-1998. It is important to note that the preferences we
      study are hypothetical, as in Israel no choice is offered and donor matching is
      performed exclusively by doctors. (2) Three comparisons serve as vehicles for
      characterizing the gaps between the natural and the consumer model: women's
      preferences regarding the donor's appearance vs. their male partners' appearance;
      men's preferences vs. their own features; single women's preferences vs. those of
      married ones. The paper ends with a discussion of the social implications of
      democratized DI on family, gender power relations and social hegemony.

PMID- 11824914
TI  - Health care switching behaviour of malaria patients in a Kenyan rural community.
AB  - Patients ordinarily use multiple sources of health care. This study reveals the
      transitions patients in a rural region of Gusii, Kenya are likely to make beyond
      the homestead in their search for alternatives to combat malaria. Malaria is a
      very common health problem in the region resulting in enormous human and economic
      losses. Data on health care seeking behaviour were collected over a 10-month
      period. The primary data for this paper is from malaria-focused ethnographic
      interviews with 35 adults (18 women and 17 men). Results show that patients are
      more likely to start with self-treatment at home as they wait for a time during
      which they observe their progress. This allows them to minimise expenditure
      incurred as a result of the sickness. They are more likely to choose treatments
      available outside the home during subsequent decisions. The decisions include
      visiting a private health care practitioner, a government health centre or going
      to a hospital when the situation gets desperate. Knowledge and duration of
      sickness, the anticipated cost of treatment. and a patient's judgement of the
      intensity of sickness determine their choice of treatment.

PMID- 11824915
TI  - Use of indigenous and indigenised medicines to enhance personal well-being: a
      South African case study.
AB  - An estimated 27 million South Africans use indigenous medicines (Mander, 1997,
      Medicinal plant marketing and strategies for sustaining the plant supply in the
      Bushbuckridge area and Mpumalanga Province. Institute for Natural Resources,
      University of Natal. Pietermaritzburg, South Africa). Although herbal remedies
      are freely available in amayeza stores, or Xhosa chemists, for self-medication,
      little is known about the motivations of consumers. According to African belief
      systems, good health is holistic and extends to the person's social environment.
      The paper makes a distinction between traditional medicines which are used to
      enhance personal well-being generally and for cultural purposes, on the one hand,
      and medicines used to treat physical conditions only, on the other. Drawing on an
      eight-month study of Xhosa chemists in Eastern Cape Province, South Africa, in
      1996, the paper identifies 90 medicines in stock which are used to enhance
      personal well-being. Just under one-third of all purchases were of medicines to
      enhance well-being. Remedies particularly popular included medicines believed to
      ward off evil spirits and bring good luck. The protection of infants with
      medicines which repel evil spirits is a common practice. Consumer behaviours
      indicate that the range of medicines available is increased by indigenisation of
      manufactured traditional medicines and cross-cultural borrowing. Case studies
      confirm that self- and infant medication with indigenous remedies augmented by
      indigenised medicines plays an important role in primary health care by allaying
      the fears and anxieties of everyday life within the Xhosa belief system. thereby
      promoting personal well-being.

PMID- 11824916
TI  - The doctor as God's mechanic? Beliefs in the Southeastern United States.
AB  - Spiritual practice and beliefs related to healing are described using data from a
      telephone survey. Questions in the survey address the practice of prayer and
      spiritual beliefs related to healing. Questions explore belief in miracles, that
      God acts through religious healers, the importance of God's will in healing, and
      that God acts through physicians. Questions also ask whether people discuss
      spiritual concerns with their physician and whether they would want to if
      seriously ill. We create a composite index to compare religious faith in healing
      across race, gender, education, income denomination, and health status. Logistic
      regression predicts types of patients who believe God acts through physicians and
      those inclined to discuss spiritual concerns when ill. The most important
      findings are that: 80% of respondents believe God acts through physicians to cure
      illness, 40% believe God's will is the most important factor in recovery, and
      spiritual faith in healing is stronger among women. African-Americans,
      Evangelical Protestants, the poorer, sicker, and less educated. Those who believe
      that God acts through physicians are more likely to be African-American than
      White (OR = 1.9) and 55 or older (OR = 3.5). Those who discuss spiritual concerns
      with a physician are more likely to be female (OR = 1.9) and in poor health (OR =
      2.1). Although 69% say they would want to speak to someone about spiritual
      concerns if seriously ill, only 3% would choose to speak to a physician. We
      conclude that religious faith in healing is prevalent and strong in the southern
      United States and that most people believe that God acts through doctors.
      Knowledge of the phenomena and variation across the population can guide inquiry
      into the spiritual concerns of patients.

PMID- 11824917
TI  - A social and demographic study of Tibetan refugees in India.
AB  - The social and demographic characteristics of approximately 65,000 Tibetan
      refugees in India were determined from data collected 1994-1996. Approximately
      55,000 refugees were living in 37 settlements widely distributed around India.
      The remaining 10,000 refugees were monks living in monasteries associated with
      some of the settlements, mostly in the south of India. In the settlements, a
      community-based surveillance system was established and data were collected by
      trained community health workers in house to house visits. In the monasteries,
      data were collected by the community health workers in monthly interviews with a
      designated liaison monk at each monastery. These data indicated little
      immigration of new civilian refugees in the past 10 years into the settlements
      but a steady influx of new monks into the monasteries. The age distribution in
      the settlements showed a prominent mode in the 15-25 year age range, a declining
      birth rate, and an increasing proportion of elderly. In general, refugees born in
      India were educated through secondary school, while refugees born in Tibet were
      often illiterate. The principle occupations were education involving 27%
      (including students), farming, 16%. and sweater selling, 6.5%; another 6.5% were
      too young or too old for employment, and only 2.4% were unemployed. The overall
      crude birth rate was determined to be relatively low at 16.8/1000. although this
      may underestimate the true figure. Infant mortality varied from 20 to 35/1000
      live births in the different regions. Child vaccination programs cover less than
      50% of the population. The burden of illness in this society was mainly
      characterized by diarrhoea. skin infections, respiratory infections, fevers, and,
      among the elderly. joint pains and cardiovascular problems. Although calculated
      death rates were unrealistically low, due to under-reporting, causes of death,
      derived from "verbal autopsies", were mainly cancer, tuberculosis, accidents,
      cirrhosis and heart disease in order of decreasing frequency. Overall, the
      sociodemographic and health characteristics of this population appear to be in
      transition from those typical of the least developed countries to those typical
      of middle income and more affluent societies.

PMID- 11824918
TI  - Tuberculosis among Tibetan refugees in India.
AB  - Tuberculosis (TB) is a major public health problem among Tibetan refugees in
      India. To determine the incidence of and risk factors for TB among Tibetan
      refugees in India, data on TB were included in the demographic and health
      surveillance project carried out by the Tibetan government-in-exile in Dharamsala
      from 1994 to 1996. Risk factor and morbidity data were determined by baseline and
      monthly follow-up home visits, and reported TB was confirmed by clinic records.
      The surveillance covered approximately 90% of the refugees in civilian
      settlements and approximately 70% of the monks in monasteries. In the settlement
      population, TB incidence was extraordinarily high in the settlement population,
      10.9/ 1,000 in 1994. but decreased to 7.7/1,000 in 1996. Incidence rates varied
      between regions, age groups, and occupational groups, being highest in the Doon
      Valley (14.8/1,000). in sweater sellers (16.7/1,000), and in the unemployed
      (23/1,000). Among monastery monks, incidence rates were even higher than in the
      settlements, averaging 17.2/1,000 over the 3-year period. The proportion of
      patients without sputum results and variation in the proportion of smear positive
      cases indicated inadequate use and poor quality of laboratory services. India's
      Revised National Tuberculosis Control Program, based on WHO-recommendations, has
      been highly successful in pilot districts and is being extended to the whole
      country. This program should be adopted promptly by the health care system
      serving Tibetan refugees and vigorously implemented among the refugee population.

PMID- 11824919
TI  - Dignity in the terminally ill: a developing empirical model.
AB  - Despite use of the term dignity in arguments for and against a patient's self
      governance in matters pertaining to death, there is little empirical research on
      how this term has been used by patients who are nearing death. The objective of
      this study was to determine how dying patients understand and define the term
      dignity, in order to develop a model of dignity in the terminally ill. A semi
      structured interview was designed to explore how patients cope with their
      advanced cancer and to detail their perceptions of dignity. Interviews were
      audiotaped and transcribed verbatim. A consecutive sample of 50 consenting
      patients with advanced terminal cancer were recruited over a 15-month period of
      time from an urban extended care hospital housing a specialized unit for
      palliative care. This unit provides both inpatient services. and coordinates end
      of-life care community based programming. Data were analysed using latent content
      analysis and constant comparison techniques. Four members of the research team
      independently coded the transcribed data, to develop conceptually meaningful
      categories of responses. Operational definitions were written for major
      categories, themes and sub-themes. Three major categories emerged from the
      qualitative analysis, including illness-related concerns; dignity conserving
      repertoire; and social dignity inventory. These broad categories and their
      carefully defined themes and sub-themes form the foundation for an emerging model
      of dignity amongst the dying. The concept of dignity and the dignity model offer
      a way of understanding how patients face advancing terminal illness. This will
      serve to promote dignity and the quality of life of patients nearing death.

PMID- 11824920
TI  - 'The cold hard facts' immunisation and vaccine preventable diseases in
      Australia's newsprint media 1993-1998.
AB  - The news media have the potential to influence public perceptions about childhood
      vaccination. Research has quantified the extent of positive news reportage on
      immunisation but no studies have explored the rhetorical nature and the core
      appeals that characterise positive reportage. To complement our previous research
      on the rhetorical nature of anti-immunisation reportage, this paper reviews
      positive coverage of immunisation in over four and a half years of Australian
      newsprint media. Three core topics dominated the reportage; the problem of
      vaccine preventable diseases and low immunisation rates, notions of who is
      responsible and the implied solutions. The threat of vaccine preventable diseases
      was conveyed using panic language, disease personification, quantification
      rhetoric, stories of personal tragedies and portentous tales from yesteryear.
      Attribution for low immunisation rates ranged from blaming parents to blaming
      lack of government coordination. However, most blame framed individuals as
      responsible. The most popular spokespersons were representatives of professional
      medical bodies who tended to be cast as voices of authority, castigating the
      ignorance and apathy of parents. Urging of compulsory vaccination, pleas for
      parents to immunise their children and the provision of information about vaccine
      preventable diseases were the most frequently occurring implied solutions.
      Immunisation was promoted as a modern medical miracle, health professionals were
      portrayed as soldiers in the fight against killer diseases and urges to immunise
      were usually conveyed through the use of stern directives. Understanding how
      immunisation messages are framed in the media and the core values to which those
      messages appeal highlights opportunities for media advocates to enhance desired
      messages and reframe those which are considered antipathetic to the goals of
      public health advocacy.

PMID- 11824921
TI  - Socio-cultural implications of changing organizational technologies in the
      provision of care.
AB  - Technology refers to inputs (machines, bureaucratic procedures, management
      strategies) organized to achieve specified outcomes. Such inputs and how they are
      used arise from socio-cultural conditions and in turn influence social behavior
      and values. Advances in medical technology are due to the high value populations
      place on health, emerging developments in science (also a cultural product). and
      from the opportunities and incentives the society gives to varying stakeholders.
      In the United States for example, the development and uses of medical technology
      are shaped by faith in marketplace competition, technological progress, activism,
      choice and consumerism. This constellation of values has resulted in very rapid
      growth and dissemination of hardware and related procedures whose costs pose
      significant financial dilemmas. In response, a range of management technologies
      have been developed to restrain the excesses of intervention but, because they
      are counter to many prevailing values and interests, they have led to much
      tension and a social backlash. Resolving these rationing tensions--which are
      rarely acknowledged as such--is a major challenge in American medical care and in
      much of the world. In the context of American social values, once new preventive
      or treatment technologies are introduced, they take patients on treatment
      trajectories that are difficult to control and which result in many being labeled
      with diagnoses they do not have and receiving interventions they do not need.
      Major efforts are under way to increase the sophistication of consumers of health
      care in a manner consistent with evidence-based medicine but these face
      significant barriers. Underlying what at first appears as simply technical
      barriers are the particular social and cultural influences on how people acquire
      and use information, the sources they trust and distrust, and the types of
      information they find credible and relevant to their situations. In short, the
      competition between new preventive and treatment technologies and managed care
      technologies is at its heart a culture war.

PMID- 11824922
TI  - Transparency and selfhood: Utopia and the informed body.
AB  - One aspect of the development of a health-orientated consumer culture is the
      growth of self-screening and self-diagnosis among the lay public--e.g. over-the
      counter diagnostic tests, computerized health assessments. DIY genetic tests.
      This trend is interpreted as the expression of a distinctively postmodern
      'utopian' impulse. Postmodernity's inwardly directed gaze has replaced the
      communitarian vision of modernity. In the absence of overarching visions, the
      postmodern utopian telos becomes the attainment of a perfect. imperishable body.
      Somatopia is the collective expression of these privatized and personalized body
      projects. The accomplishment and authentication of these body projects
      necessitates the creation of a 'transparent body'. This 'transparent body' is
      enabled and constructed by developments in information and medical technologies.
      The political and health implications of the transparent, 'informed' body are
      explored.

PMID- 11824923
TI  - Women's social networks and child survival in Mali.
AB  - This paper explores the influence of women's social networks on child survival
      through a comparative investigation of two ethnic groups in Mali, West Africa.
      Data are drawn from a study of women's social networks and health conducted
      during the period 1996-97. Separate samples of 500 ever-married women aged 15-49
      were surveyed at two geographically distinct sites representing Bamanan and Fulbe
      populations respectively. Consistent with known differences in economic risk,
      household structure, and cultural norms, descriptive analysis reveals a greater
      probability of child death among the Fulbe, and a larger mean size of total,
      material, practical and cognitive networks among the Bamanan. Cox regression
      models are used to examine the association between social network size, function
      and composition and the odds of child death (1-5 years). Among the various
      biological, household and community-level variables tested in the basic model,
      spacing exerts an expected negative effect on the odds of child death in both
      groups, while household SES predicts child survival only among Fulbe children.
      When variables representing the educational and psychosocial attributes of the
      mother are included, no effects are detected in either group. Controlling for
      these factors, the size of total, practical, cognitive and emotional networks are
      found to significantly increase the odds of child survival among the Fulbe only.
      Compositional variables, such as the extent to which natal kin, non-kin or
      husbands figure in a woman's network, nor the degree to which networks are
      located within household yield any significant results for the Fulbe. Among
      Bamanan women, however, the higher the proportion of network members living in
      the household, the lower the odds of child death. The paper concludes by
      discussing the methodological, conceptual and practical implications of these
      findings.

PMID- 11824924
TI  - Women who sell sex in a Ugandan trading town: life histories, survival strategies
      and risk.
AB  - Little is known about the background of commercial sex workers in Africa. This
      study investigated how women in a trading town on the trans-Africa highway in
      southwest Uganda become involved in commercial sex work, which factors contribute
      to their economic success or lack of success, and what effect life trajectories
      and economic success have on negotiating power and risk behaviour. Over the
      course of two years detailed life histories of 34 women were collected through
      recording open, in-depth interviews, the collection of sexual and income and
      expenditure diaries, visits to the women's native villages, and participant
      observation. The women share similar disadvantaged backgrounds and this has
      played a role in their move into commercial sex. They have divergent experiences,
      however, in their utilisation of opportunities and in the level of success they
      achieve. They have developed different life styles and a variety of ways of
      dealing with sexual relationships. Three groups of women were identified: (1)
      women who work in the back-street bars, have no capital of their own and are
      almost entirely dependent on selling sex for their livelihood; (2) waitresses in
      the bars along the main road who engage in a more institutionalised kind of
      commercial sex, often mediated by middlemen and (3) the more successful
      entrepreneurs who earn money from their own bars as well as from commercial sex.
      The three groups had different risk profiles. Due partly to their financial
      independence from men, women in the latter group have taken control of sexual
      relationships and can negotiate good sexual deals for themselves, both
      financially and in terms of safe sex. The poorer women were more vulnerable and
      less able to negotiate safer sex. A disadvantaged background and restricted
      access to economic resources are the major reasons for women gravitating to
      commercial sex work. Various aspects of personality play a role in utilising
      income from commercial sex to set up an economic basis that then makes the
      selling of sex unnecessary. This has implications for interventions, and part of
      the longer-term solution should lie in improving the economic position of women
      vis-a-vis men.

PMID- 11824925
TI  - The reproductive and occupational health of women street vendors in Johannesburg,
      South Africa.
AB  - While the informal sector is rapidly emerging as the major source of employment
      in poor countries, little attention has been paid to the health hazards
      encountered by workers in this sector. Women, the majority of informal sector
      workers in most parts of the world, are particularly at risk. This paper reports
      on 422 women street vendors trading in 323 city blocks in Johannesburg, South
      Africa. The median age was 29 years, 66% were single, 29% had primary education
      and 58% had secondary schooling. Foreign-born women accounted for 15% of the
      sample and a further 59% of the women were not born in Johannesburg. More than a
      third of the women did not work for themselves and 48% earned <115 US dollars per
      month. Fertility was positively related to age and inversely related to
      education, while reported infertility was related to gynaecological disease. More
      than half the women used, mainly injectable, contraceptives and only 5%
      reportedly had PAP smears taken. Most of the women sold food and clothing, 51%
      lifted heavy weights and a small proportion of the women worked with fire. Over
      half of the women (54%), mainly those over 40 years and the self-employed,
      complained of a work-related illness or injury, mainly burns, cuts, headaches and
      musculoskeletal problems. The type of health problem was related to age and 32%
      had received treatment. More than half (52%) of the respondents reported that
      they were not comfortable with the working environment, for reasons ranging from
      lack of shelter and dirt (34%), noise (26%) and having to clean the area
      themselves (24%). While only 2% reported that they felt unsafe, violence and
      abuse was ever present. Approximately one in four women reported some form of
      abuse, either verbal or physical, while 7% reported that they had been sexually
      harassed. A substantial proportion (29%) of the women reported that they had been
      robbed of money or goods while trading in the streets. The implications of these
      findings are discussed.

PMID- 11824926
TI  - The decline of female circumcision in Egypt: evidence and interpretation.
AB  - Female circumcision is widespread in Egypt. Research suggests that the practice
      persists because of a belief that circumcision will moderate female sexuality,
      that it will assure a girl's marriagability, and that it is sanctioned by Islam.
      Using data from a nationally representative survey of adolescents, this paper
      investigates the prevalence and social correlates of circumcision among girls
      aged 10-19, the circumstances surrounding the procedure, and the attitudes of
      adolescents towards it. While the vast majority of adolescents are circumcised, a
      life table analysis indicates that girls today are at least 10 percentage points
      less likely to undergo female circumcision than were their mothers. Circumcision
      may have begun to decline prior to the time when the current cohort of girls were
      at risk; however, the data hint at a temporal association between the decline and
      the 1994 International Conference on Population and Development (ICPD) in Cairo,
      a time when the campaign against circumcision gained momentum. Over half of
      circumcised girls reported that the procedure was performed by a physician or
      nurse rather than a traditional practitioner. This represents a substantial
      increase over rates of "medicalized" circumcision found among earlier cohorts of
      Egyptian women. Even among circumcised girls, support for the practice is by no
      means universal, with 14 percent saying they think the procedure is unnecessary
      and a further 28 percent expressing ambivalence. A multivariate analysis
      indicates that girls who have been or are currently in school, who live in urban
      governorates, and who are older are more likely to believe that circumcision is
      not obligatory. When the analysis includes boys as well as uncircumcised girls, a
      large gender gap emerges, with boys considerably more supportive of the practice
      than are their female counterparts.

PMID- 11824927
TI  - Severity of musculoskeletal pain: relations to socioeconomic inequality.
AB  - The main aim of the study was to investigate possible associations between
      severity of non-inflammatory musculoskeletal pain and residential areas of
      contrasting socioeconomic status. A 4-page questionnaire inquiring about
      musculoskeletal pain, and also physical disability, mental health, life
      satisfaction and use of health services was sent to 10,000 randomly selected
      adults in Oslo, Norway. For the purpose of this study, we analysed data from
      respondents living in two socioeconomically contrasting areas of the city.
      Measures of pain (intensity, duration, localisation), physical disability (MHAQ),
      mental distress (SCL-5, sleep disturbances), life satisfaction and use of health
      services (general practitioner, rheumatologist, medication, involvement in and
      satisfaction with own care) were compared between respondents living in the two
      areas (n = 870 and n = 892 respondents, respectively) of whom 493 in each area
      reported non-inflammatory musculoskeletal pain. Multiple regression analyses
      adjusting for age revealed that living in the less affluent area was associated
      with strong and widespread pain, with high levels of physical disability and
      mental distress and with low life satisfaction. Living in the less affluent area
      was also associated with frequent use of analgesics and with low level of
      involvement in own health care, after adjustment for age, pain intensity and
      levels of physical disability and mental distress. Non-inflammatory
      musculoskeletal pain seems to be a more serious condition in a population living
      in a less affluent residential area compared with a more affluent one, even in an
      egalitarian society like Norway. Increased disease severity may thus amplify the
      impact of greater chronic morbidity in the disadvantaged part of the population.
      This should have implications for health care provision if the goal is treatment
      according to needs.

PMID- 11824928
TI  - "Tooth worms", poverty tattoos and dental care conflicts in Northeast Brazil.
AB  - While medical anthropologists have studied doctor-patient clinical conflicts
      during the last 25-30 years, dentist-patient communication clashes have received
      scant attention to date. Besides structural barriers and power inequities, such
      conceptual differences further dehumanize dental care and lower service quality.
      Potential for dentist-patient discordance is greater in developing regions--such
      as Northeast Brazil--where there exists a wider socio-economic gap between
      professionals and laypersons. A critical anthropological evaluation of oral
      health services quality is undertaken in two rural communities in Ceara, Brazil
      where the PAHO-inspired Local Oral Health Inversion of Attention Program was
      implemented in 1994. This 6-month qualitative field study utilized ethnographic
      interviews with key informants, participant-observation and projective techniques
      to probe professionals' and patients' explanatory models (EMs) of oral health.
      Despite the recent expansion of services into rural regions, the authors conclude
      that the quality of dental care remains problematic. Patients' culturally
      constructed EMs of teeth rotted (estraga) by "tooth worms" (lagartas) differ
      substantively from dentists' model of dental decay by Streptococcus mutans.
      "Exploding chins" (queixo estourado), "spoiled, rotting teeth" (dente pjdi) and
      "false plates" or teeth (chapas) tattoo and stigmatize the poor, reinforcing
      gross class inequities. Dentists' dominant discourse largely ignores lay logic,
      ridicules popular practices and de-legitimates, even castigates, popular healers
      despite their pivotal role in primary oral health care. Poor parents are not only
      barred from clinics but are blamed for children's rotten teeth. In sum, universal
      access to dental care is more a myth (even nightmare) than a reality. Dentists
      all too often "avert"--not "invert"--attention from poor Brazilian patients. In
      order to improve oral health in this setting, both "societal decay" and bacteria
      laden plaque deposits must be removed.

PMID- 11824929
TI  - Historical trends of survival among widows and widowers.
AB  - One of the most consistent findings in social demography is that recently widowed
      individuals, male or female, have higher rates of mortality than comparable
      married persons. These results are based generally on contemporary studies in
      developed nations where life expectancy is high. Because of data limitations,
      there are few studies available to determine whether these findings also occur
      when mortality rates were higher. This study uses the Utah Population Database
      that was developed from extensive family genealogies and now linked to Utah death
      certificates. These data make it possible to employ life course analysis of four
      marriage cohorts extending from 1860 through 1904 with mortality follow-up to
      1990. This approach is used to compare mortality risks of widowed males and
      females relative to comparable married individuals. Covariates included in the
      study are remarriage, as well as religion and number of children ever born; these
      are all hypothesized to have protective effects on mortality risks for widowed
      men and women. Analysis of these data indicates that there are significant
      differences in the mortality risk for widowed men and women, and it is widowed
      men who have an excess risk of dying in every cohort and nearly every age. A
      consistent pattern of excess mortality in the comparison of married and widowed
      women was not observed. There are significant female and male differences in the
      effect of religion which was treated as a proxy for life style and social
      support: however, remarriage as a proxy for social support has similar protective
      effects on the surviving spouse.

PMID- 11824930
TI  - A socio-legal and economic analysis of contracting in the NHS internal market
      using a case study of contracting for district nursing.
AB  - The introduction of an internal market in the National Health Service (NHS) in
      the United Kingdom necessitated the use of contracts between purchasers and
      providers. Little thought was given to the nature of these contracts by policy
      makers, who appeared to assume that the contracts could conform to the classical,
      complete model. This paper uses socio-legal and economic theories of contract
      (which provide an alternative model of relational contracts, in contrast to
      classical contracts) to explore how realistic that assumption was. An analysis of
      the institutional context in which the contracts were made is provided, including
      a legal analysis of the relevant legislation. Contracting by health authorities
      and GP fundholders is examined, using the results of a recent case study of
      contracting for district nursing services carried out in a health authority in
      Greater London. The results show that classical contracting is an inappropriate
      model for NHS contracts, but that relational contracting is not an entirely
      appropriate model either. Contracting was found to have increased the
      accountability of providers in respect of some financial matters, but not in
      respect of the quality of district nursing services. There are negative
      implications for the use of contracting in publicly financed health services-
      hierarchies may be more efficient (as lower transaction costs can be incurred)
      and possibly more effective in improving quality of care.

PMID- 11824931
TI  - Dual job holding practitioners in Bangladesh: an exploration.
AB  - This paper analyses the system of financial and non-financial incentives
      underlying job preferences of doctors in Bangladesh who work both in government
      health services and in private practice. The study is based on a survey of 100
      government-employed doctors with private practice, across different levels of
      care and geographical areas. In-depth interviews were carried out in a sub-sample
      of 28 respondents. The study explores the beliefs and attitudes towards the
      arrangements of joint private/public practice, establishes profiles of fee levels
      and earnings and examines the options to change the incentive system in a way
      that ensures an increased involvement of dual job holding practitioners in the
      priority areas of care. Consultation fees were Tk120 on average (range Tk20-300)
      and found to be correlated with the qualification of the practice owner and the
      type of service offered. A majority of the respondents reported at least to
      double their government income by engaging in private practice. Significant
      predictors of total income included the number of patients seen in private
      practice (p=0.000), employment in a secondary or tertiary care facility (p=0.001)
      and ownership of premises for private practice (p=0.033). Age was found to be
      marginally significant (p=0.084). No association was found between total income
      and specialisation, private practice costs, level of government salary or a
      degree from abroad. The data suggest that doctors have adopted individual
      strategies to accommodate the advantages of both government employment and
      private practice in their career development, thus maximising benefit from the
      incentives provided to them e.g. status of a government job, and minimising
      opportunity costs of economic losses e.g. lower salaries. Commitment to
      government services was found to be greater among doctors in primary health care
      who reported they would give up private practice if paid a higher salary. Among
      doctors in secondary and tertiary care, the propensity to give up private
      practice was found to be low. Financial incentives that aim to increase numbers
      of doctors in rural areas, such as a non-private-practice allowance, are more
      likely to be appreciated by doctors who are at the beginning of their career.
      Improved training and career opportunities also appear to be of high importance
      for job satisfaction. Policy changes to ensure a better resource allocation to
      the priority areas of the health sector have to reflect an understanding of the
      incentives generated by the organisational and financial context within which
      dual job holding practitioners operate.

PMID- 11824932
TI  - Responsibility and cancer disclosure in Japan.
AB  - In Japan, as in many countries around the world, cancer patients are often not
      told the truth about their illness. Despite polls showing a majority of those
      surveyed wish to be told, surveys of physicians indicate only a small percentage
      will tell, especially when the cancer is advanced or terminal. We interviewed
      physicians from various specialties with experience managing advanced or terminal
      cancer patients to investigate their approaches to cancer disclosure. Our
      analysis reveals physicians divide into two groups: those who usually do not tell
      (non-tellers) such patients and those who usually do tell (tellers). Non-tellers
      reported the shock of disclosure inhibits telling patients, families' wishes for
      non-disclosure cannot be ignored, and most patients themselves do not wish to be
      told. Tellers asserted disclosure is unavoidable and patients want to be told,
      few problems result when they tell, and telling has many advantages such as not
      having to lie to the patient. Despite the experience of non-tellers, most
      physicians continue to follow the traditional approach, for advanced or terminal
      cancers. Physicians, as well as families and patients, display an aversion to
      taking responsibility for the potential risks of disclosure, and this may
      perpetuate the status quo.

PMID- 11824933
TI  - Constructing an account by contrast in counselling for childhood genetic testing.
AB  - Genetic counselling sessions are rich and complex sites of accounting practices
      for decision-making in which clinicians are meant to facilitate rather than
      control the decisions made by their clients. This often means the adoption of a
      non-directive stance as counsellors lay out various possible courses of action
      from which the client can choose, while both client and counsellor may need to
      bear in mind a wide range of practical and ethical issues. With regard to
      childhood predictive testing, the complexity of decision-making is manifest not
      only in relation to the severity of the genetic condition being discussed, but
      also in terms of who controls the information, who might be affected by it and
      who makes decisions on whose behalf. In this paper we use discourse analytic
      methods to examine a single case where the clinician and the parent negotiate
      decisions about childhood testing and the extent to which the parent can
      influence this process. In discursive terms, we show how the child's future
      autonomy is juxtaposed against the parent's current rights. In order fully to
      understand the various characters and events deployed in the accounting practices
      of the parent and the genetic counsellor, we focus on one rhetorical device,
      i.e., contrast, as it is manifest at different levels of representation. We
      conclude that the interplay between a selected set of the contrast pairs
      contributes towards recursive interactional patterns as far as non-directive
      counselling is concerned, and consequently has implications for procedural
      outcomes.

PMID- 11824934
TI  - Immigrants from Chernobyl-affected areas in Israel: the link between health and
      social adjustment.
AB  - The concept of cumulative adversity is a useful tool in the study of migration
      under chronic stress from past traumas. Drawing on this concept, the study
      explored long-term health and psychosocial effects of past radiation exposure
      among survivors of the Chernobyl nuclear disaster who immigrated to Israel during
      the 1990s. Self-rated health status and indicators of social adjustment were
      compared in two groups of Russian immigrants: 180 persons from Chernobyl-affected
      areas and 200 immigrants from other areas of the former USSR. The semi-structured
      questionnaire was administered by Russian-speaking sociology students and
      analyzed by both quantitative and qualitative methods. In line with earlier
      research, both the somatic and mental health of Chernobyl survivors were
      significantly worse than in other immigrants of the same gender and age; a
      significant share of reported health problems were probably psychosomatic.
      Depression, sense of stigma and cancer-related anxiety were more prevalent in the
      study group. Immigrants from contaminated areas tended to use more health
      services (both conventional and alternative), but were less satisfied with their
      quality and providers' attitude. The link between perceived health impairment and
      poorer social accommodation in the host country has been confirmed: Chernobyl
      area immigrants experienced more severe occupational downgrading and were more
      disappointed with the results of their resettlement than other immigrants.

PMID- 11824935
TI  - Actions of putative chloride channel blocking agents on canine lower esophageal
      sphincter (LES).
AB  - Niflumic acid (NA), a putative Cl(-)-channel blocker, has provided
      pharmacological evidence that Cl(-)-channel closures mediate hyperpolarization
      caused by NO in gastrointestinal smooth muscle. However, NA caused concentration
      dependent relaxation of canine lower esophageal sphincter (LES) and failed to
      inhibit NO-mediated relaxations. DIDS also did not inhibit NO-mediated
      relaxations, but did abolish them when present with 20 mM TEA (tetraethyl
      ammonium ion), which was also ineffective alone. TEA reversed NA-induced
      relaxations, but with NA it did not inhibit NO-mediated relaxations. We
      investigated the modes of action of these agents further. Neither nerve-function
      block nor block of NOS activity affected the inhibition of LES tone by NA. In
      patch-clamp studies, NA increased outward currents from -30 to + 90 mV when
      [Ca2+]pipette was 50 nM. This was prevented by 20 mM TEA, but not by prior
      inhibition of NOS. At 200 nM [Ca2+]pipette, TEA markedly reduced outward
      currents, but did not prevent the increase from subsequent NA. In contrast, under
      similar conditions, application of DIDS after 20 mM TEA further reduced outward
      currents. When the patch pipette contained CsCl and TEA to block K+ currents, NA
      had no significant effect on currents between -50 and +90 mV. Thus, NA acted by
      opening K+ channels: some TEA-sensitive and some not. It had no detectable effect
      on currents when K+ channels were blocked. We conclude that NA is an unreliable
      pharmacological tool to evaluate Cl(-)-channel contributions to smooth muscle
      function. DIDS did not open K+ channels. Decreases in outward currents from DIDS
      may result from inhibition of K+ currents or currents carried by Cl- at
      depolarized membrane potentials.

PMID- 11824936
TI  - Effect of altered physical loading on bone and muscle in the forearm.
AB  - Cast immobilization of injured forearms is common clinical practice yet little is
      known about the effect of reduced skeletal loading in the absence of pathology.
      This study reports the changes in the forearms of nine healthy young adults owing
      to six weeks in a plaster cast followed by 1 year of either habitual activity or
      a strengthening program. Both groups exhibited similar patterns of change in
      wrist mobility, forearm muscle strength, and bone variables. Because of small
      sample size and poor compliance with the exercise protocol, no conclusions can be
      drawn about the effect of exercise. In all subjects, reduced loading caused a
      decrease in wrist mobility (p < 0.02) and grip strength (p = 0.01) with full
      recovery following 3 months of remobilization. Six months after removing the
      cast, bone size was reduced in the middle region of the radius (p = 0.02) and
      recovered after 1 year of remobilization. Given that radial bone mass tended to
      decrease while bone density was unchanged, we conclude that the effect of casting
      was modulated by changes in gross bone morphology rather than in material
      characteristics.

PMID- 11824938
TI  - The vaso-contractile action of zooxanthellatoxin-B from a marine dinoflagellate
      is mediated via Ca2+ influx in the rabbit aorta.
AB  - We previously showed that zooxanthellatoxin-B, isolated from dinoflagellate,
      caused a sustained contraction of the aorta in an external Ca2+-dependent manner.
      To clarify the role of Ca2+ in this action, we examined the effects of
      zooxanthellatoxin-B as well as a depolarizing stimulus (60 mM KCl), using the
      simultaneous recording for cytosolic Ca2+ level (fura-2) and developed tension in
      the rabbit aorta. KCl (60 mM) elicited a rapid cytosolic Ca2+ elevation followed
      by a pronounced contraction, and time required for half-maximum contraction was 2
      min. Zooxanthellatoxin-B caused an increase in cytosolic Ca2+ followed by a
      gradual contraction, with a time for half-maximum contraction of 5-10 min in a
      concentration-dependent manner. We found a strong correlation between Ca2+
      elevation and the contraction in zooxanthellatoxin-B action. In a Ca2+-free
      solution, zooxanthellatoxin-B caused neither the contraction nor the increase in
      cytosolic Ca2+. Furthermore, both pre- and post-treatment with verapamil, a
      voltage-operated Ca2+-channel blocker, partially suppressed both an increase in
      cytosolic Ca2+ and the contraction by zooxanthellatoxin-B. Zooxanthellatoxin-B
      induced contraction was also inhibited by other voltage-operated Ca2+-channel
      blockers: nifedipine or diltiazem. These results suggest that zooxanthellatoxin-B
      elicited contraction is caused by a Ca2+ influx into the smooth muscle cells,
      partially via voltage-operated Ca2+ channels.

PMID- 11824937
TI  - Active transport of alanine by the neutral amino-acid exchanger ASCT1.
AB  - ASCT1 protein is a member of the glutamate transporter superfamily, which shows
      system ASC selectivity and properties and has been characterized as a Na+
      dependent neutral amino-acid exchanger. Here, by using ASCT1-expressing oocytes,
      the uptake of alanine and glutamate was measured to investigate ASCT1's ability
      to mediate a concentrative transport of alanine, ASCT1's sodium dependence, and
      the influence of pH on the mutual inhibition between alanine and glutamate.
      Alanine uptake was measured after 30 min incubation. Kinetic analysis of the Na+
      dependence of alanine uptake showed an apparent K0.5 (affinity constant) value
      for Na+ of 23.1 +/- 4.3 mM (mean +/- SE). Concentration dependence of alanine
      uptake was tested at 100 and 1 mM Na+, with apparent K0.5 values of 0.16 +/- 0.04
      and 1.8 +/- 0.4 mM, respectively, at pH 7.5, and 0.21 +/- 0.06 and 1.9 +/- 0.3 mM
      at pH 6. Vmax was not modified between 100 and 1 mM Na+ at either pH. ASCT1
      actively transports alanine and accumulates it in the cytosol even when the Na+
      concentration in the medium was as low as 1-3 mM. 22Na uptake studies revealed
      that Na+ transport was stimulated by the presence of alanine in the medium. Our
      results demonstrate that ASCT1 is able to mediate a concentrative transport of
      alanine, which is Na+-dependent but not coupled to the Na+ gradient.

PMID- 11824939
TI  - The process of cardiorespiratory autoresuscitation in intact newborn rats.
AB  - To examine the process of spontaneous autoresuscitation and the recovery of the
      hypoxic ventilatory response (HVR) after prolonged anoxia, we monitored
      respiratory frequency (f, by body plethysmography) and heart rate (HR, by ECG) in
      intact newborn rats (n = 12, day 2-4) before, during, and after 100% N2 exposure.
      The rat before anoxia showed signs of HVR: f changes at acute hypoxia (10% O2)
      and hyperoxia (100% O2). During anoxia, the spontaneous respiratory movement
      "gasping" appeared for 21 min (mean). At O2 restoration (with 100% O2), gasping
      stopped and no respiratory flow was detected for 1 min. One rat failed to
      autoresuscitate and had heart arrhythmia during the transient apnea, but 11 rats
      recovered respiration after the HR acceleration. Despite the successful
      autoresuscitation, the rats did not show HVR at 10 min into the recovery period
      and the recovery of HVR required more than 30 min. The results indicate that O2
      inhalation is useful to trigger autoresuscitation even when the rat has already
      been in a state of profound hypoxic depression, but the rat becomes transiently
      insensitive to HVR after autoresuscitation. We estimate that reform of the
      respiratory control system in newborn rats is not yet firmly established to track
      HVR early in the recovery phase after prolonged anoxia.

PMID- 11824941
TI  - Sequence and chromosomal assignment of a human novel cDNA: similarity to gamma
      aminobutyric acid transporter.
AB  - Gamma-aminobutyric acid (GABA) is the predominant inhibitory neurotransmitter in
      the mammalian brain. Although initially thought to be confined to the central
      nervous system, GABAergic activity has also been described in other tissues
      throughout the body. In the present study, we report the cloning and localization
      of human GABA transporter cDNA and document its expression in various human
      tissues. A human liver cDNA library was initially screened by a 32P-labeled
      murine brain GABA transporter 3 (GAT-3) cDNA probe, and full-length cDNA was
      cloned by employing Marathon-Ready human kidney cDNA. The human GABA transporter
      cDNA encoded a 569 amino acid hydrophobic protein with 12 transmembrane domains
      (TMs). Search of published sequences revealed high homology with rat GAT-2,
      murine GAT-3 cDNA, human solute carrier family 6 member 13 (SLC6A13), and a human
      peripheral betaine/GABA transporter. Northern blot analyses demonstrated that the
      human GABA transporter is expressed strongly in the kidney and to a lesser extent
      in the liver and brain. The sequence was well matched with human chromosome
      12p13.3, suggesting the human GABA transporter contains 14 exons. The above
      findings confirm the existence of and further characterize a specific GABA
      transporter in human tissues.

PMID- 11824940
TI  - Role of I(K) and I(f) in the pacemaker mechanisms of sino-atrial node myocytes.
AB  - The role of I(K) (delayed rectifier current) and I(f) (hyperpolarization
      activated current) in dominant and subsidiary pacemaker ranges was studied in
      single myocytes isolated from the guinea pig sino-atrial node by means of a
      perforated patch-clamp technique. In the dominant pacemaker range (approx. -55 to
      -40 mV), I(K) tails are present whereas I(f) is not activated. In the subsidiary
      pacemaker range (approx. -80 to -70 mV), I(f) is large whereas I(K) is minimal
      and reversing. The threshold for I(f) activation is more negative at short time
      intervals. Larger or longer depolarizations to -40 mV and +20 mV deactivate I(f)
      more and are followed by faster reactivation of I(f). Steps of 200-300 ms
      duration to +20 mV completely deactivate I(f). The slope conductance decreases
      during depolarizations at -40 and +20 mV and quickly re-increases after the
      steps. The I(f) deactivation range is between -70 and +10 mV, with a V(1/2) of 
      35 mV. Depolarizations from -80 to +20 mV at a rate of 120/min limit the
      subsequent I(f) reactivation owing to the short diastole. We conclude that I(K)
      plays a predominant role in the dominant pacemaker range and I(f) does so in the
      subsidiary pacemaker range. Either pacemaker mechanism is used by sino-atrial
      node cells depending on the diastolic potential range. A previous depolarization
      markedly increases the amplitude and rate of I(f) reactivation.

PMID- 11824942
TI  - Further characterization of beta3-adrenoceptors in the guinea pig gastric fundus:
      stereoselectivity, beta-adrenoceptor alkylation, and structure-activity
      relationship.
AB  - The stereoselectivity of beta3-adrenoceptors, the effect of a beta-adrenoceptor
      alkylating agent, and the structure-activity relationship at beta3-adrenoceptors
      were investigated on the guinea pig gastric fundus. Isomeric activity ratios
      ((+)/(-)) for isomers of isoprenaline and noradrenaline were 20.9-fold and 43.7
      fold, respectively, and were less than those obtained for activation of beta1-
      and beta2-adrenoceptors in the guinea pig atria and trachea, respectively. The
      concentration-response curves to the catecholamines ((-)-isoprenaline, (-)
      noradrenaline, and (-)-adrenaline), the selective beta3-adrenoceptor agonist
      BRL37344 ((R*,R*)-(+/-)-4-[2-[(2-(3-chlorophenyl)-2
      hydroxyethyl)amino]propyl]phenoxyacetic acid sodium), and the nonconventional
      partial beta3-adrenoceptor agonist (+/-)-CGP12177A ((+/-)-[4-[3-[(1,1
      dimethylethyl) amino]-2-hydroxypropoxy]-1,3-dihydro-2H-benzimidazol-2-one]
      hydrochloride) were resistant to blockade by (+/-)-pindobind (10 microM), the
      beta-adrenoceptor alkylating agent. Furthermore, (+/-)-nadolol, which belongs to
      the aryloxypropanolamine class and has beta1- and beta2-adrenoceptor antagonistic
      characteristics, displays agonistic activity at beta3-adrenoceptors. These
      results indicate that pharmacological characteristics of the beta3-adrenoceptors
      of guinea pig gastric fundus differ from those of beta1- and beta2-adrenoceptors.
      (-)-Noradrenaline and (-)-adrenaline were more potent than dopamine and (-)
      phenylephrine, respectively. In addition, dobutamine was 22-fold more potent than
      dopamine. These results suggest that the 4-hydroxyl group at the catechol ring
      and the beta-hydroxyl group and the large moiety on the alkylamine chain
      characterized efficacy at beta3-adrenoceptors.

PMID- 11824943
TI  - An integrative, in situ approach to examining K+ flux in resting skeletal muscle.
AB  - The contributions of Na+/K+-ATPase, K+ channels, and the NaK2Cl cotransporter
      (NKCC) to total and unidirectional K+ flux were determined in mammalian skeletal
      muscle at rest. Rat hindlimbs were perfused in situ via the femoral artery with a
      bovine erythrocyte perfusion medium that contained either 86Rb or 42K, or both
      simultaneously, to determine differences in ability to trace unidirectional K+
      flux in the absence and presence of K+-flux inhibitors. In most experiments, the
      unidirectional flux of K+ into skeletal muscle (J(in)K) measured using 86Rb was 8
      10% lower than J(in)K measured using 42K. Ouabain (5 mM) was used to inhibit
      Na+/K+-ATPase activity, 0.06 mM bumetanide to inhibit NKCC activity, 1 mM
      tetracaine or 0.5 mM barium to block K+ channels, and 0.05 mM glybenclamide (GLY)
      to block ATP-sensitive K+ (K(ATP)) channels. In controls, J(in)K remained
      unchanged at 0.31 +/- 0.03 micromol x g(-1) x min(-1) during 55 min of perfusion.
      The ouabain-sensitive Na+/K+-ATPase contributed to 50 +/- 2% of basal J(in)K, K+
      channels to 47 +/- 2%, and the NKCC to 12 +/- 1%. GLY had minimal effect on
      J(in)K, and both GLY and barium inhibited unidirectional efflux of K+ (J(out)K)
      from the cell through K+ channels. Combined ouabain and tetracaine reduced J(in)K
      by 55 +/- 2%, while the combination of ouabain, tetracaine, and bumetanide
      reduced J(in)K by 67 +/- 2%, suggesting that other K+-flux pathways may be
      recruited because the combined drug effects on inhibiting J(in)K were not
      additive. The main conclusions are that the NKCC accounted for about 12% of
      J(in)K, and that K(ATP) channels accounted for nearly all of the J(out)K, in
      resting skeletal muscle in situ.

PMID- 11824944
TI  - Splenectomy has a limited role in the management of lupus with thrombocytopenia.

PMID- 11824945
TI  - Ulnar artery involvement in systemic sclerosis (scleroderma).
AB  - OBJECTIVE: Microvascular disease is one of the hallmarks of systemic sclerosis
      (SSc, scleroderma), but macrovascular involvement also exists in some patients.
      Patients with SSc may have severe Raynaud's phenomenon (RP) characterized by
      refractory digital ulcerations. We investigated if large artery involvement, that
      is, ulnar artery occlusion, has a role in the development of refractory digital
      ulcerations, and if both screening for this involvement and revascularization of
      the ulnar artery occlusive disease may improve digital ulcer healing. METHODS: A
      retrospective chart review was performed of 15 patients with SSc, all of whom had
      severe RP and digital ulceration, together with a positive Allen test and ulnar
      artery occlusive disease documented by angiography. RESULTS: Women outnumbered
      men 2:1, with limited disease predominating (7), 5 patients having diffuse
      cutaneous disease and 3 overlap syndromes. All patients had positive antinuclear
      antibody and capillary microscopy findings consistent with SSc. Antiphospholipid
      antibodies were present in 4 of 6 patients tested. Tobacco use was seen in 5
      patients, only 2 of whom were current smokers. All patients failed conventional
      medical therapy (nitrates, calcium channel blockers, antiplatelet agents) for RP
      and digital ulceration. Only 1/8 patients improved with stellate ganglion block,
      and one patient had no improvement following digital sympathectomy. Eight
      patients underwent ulnar artery revascularization combined with digital
      sympathectomy, and 8 experienced dramatic improvement in RP and healing of
      digital ulcers. CONCLUSION: An Allen test should be performed routinely on all
      SSc patients with severe RP and refractory digital ulceration to investigate the
      possibility of ulnar artery occlusive disease. If suspected ulnar artery
      occlusion is confirmed by angiography or ultrasonography, ulnar artery
      revascularization with or without digital sympathectomy should be considered in
      patients who fail conventional medical therapy.

PMID- 11824946
TI  - Gelatinase expression and activity in the synovium and skin of patients with
      erosive psoriatic arthritis.
AB  - OBJECTIVE: Matrix metalloproteinases (MMP), especially the gelatinases (MMP2,
      MMP9), have been implicated in several features of inflammatory arthritis
      including angiogenesis and bone erosions. We examined the expression and activity
      of the gelatinases and their regulators in psoriatic skin and synovium using
      tissue immunohistochemistry and a sensitive tissue based zymographic technique.
      METHODS: Lesional and perilesional skin biopsies and synovial samples obtained by
      closed needle biopsy from 15 patients with erosive psoriatic arthritis (PsA) were
      analyzed by immunohistochemistry for the expression of the gelatinases and their
      regulators, tissue inhibitor of metalloproteinase 1 and 2 (TIMP-1, TIMP-2) and
      membrane type metalloproteinases (MTI-MMP. MT2-MMP), using immunohistochemistry.
      Synovial tissue from 8 patients with erosive rheumatoid arthritis (RA) was used
      as a comparison. MMP tissue expression was quantified by 2 blinded independent
      observers. Immunohistochemical data are reported as the mean percentage positive
      cells per total nucleated cells in 10 high power fields +/- SD. Functional
      activity of the gelatinases was measured using a sensitive tissue based
      zymography technique and corrected for protein content. Zymography data are
      presented as ng/mg +/- SE. RESULTS: MMP expression was greater in the synovial
      lining layer (LL) than in the synovial sublining layer (SL) in both PsA and RA
      tissue for most MMP except collagenase I (MMPI), which was equally distributed
      between the LL and SL. Expression of MMP or their regulators did not differ
      between PsA synovial membrane (SM) and RA SM in LL. Moreover, although latent
      gelatinase A (MMP2) staining in PsA SM was equivalent to RA SM, increased
      gelatinase A activity was found in PsA SM over RA SM using zymography L82.4 (SD
      62.8) vs 10.1 (SD 1.7); p = 0.02]. Compared to PsA SM, lesional skin had lower
      levels of MT1-MMP (MMP14) (1.4 +/- 1.7 vs 15.7 +/- 8.4; p = 0.009) and MT2-MMP
      (MMP15) (12.1 +/- 8.7 vs 21.6 +/- 9.9; p = 0.001). CONCLUSION: We characterized
      the expression and activity of gelatinases in PsA and demonstrate that gelatinase
      activity in SM of PsA patients with erosive disease is comparable to if not
      greater than that in RA synovium.

PMID- 11824947
TI  - Successful short term treatment of severe undifferentiated spondyloarthropathy
      with the anti-tumor necrosis factor-alpha monoclonal antibody infliximab.
AB  - OBJECTIVE: Tumor necrosis factor-alpha (TNF-alpha) has been detected in
      sacroiliac joints of patients with spondyloarthropathies (SpA). Anti-TNF-a
      therapy has been efficacious in patients with active ankylosing spondylitis (AS)
      and psoriatic arthritis. Similar to these SpA subtypes, therapeutic options in
      undifferentiated SpA (uSpA) are also limited. We tested the efficacy of the
      monoclonal anti-TNF-alpha antibody infliximab in patients with active and severe
      uSpA in an open observation trial. METHODS: Six patients with uSpA were treated
      with 3 infusions of infliximab in a dosage of 3 (n = 3) or 5 mg/kg (n = 3) at
      Weeks 0, 2, and 6. The total observational period was 12 weeks. The Bath AS
      Disease Activity Index (BASDAI), the Functional Index (BASFI), pain on a visual
      analog scale, the Bath AS Metrology Index (BASMI), and quality of life (SF-36)
      were assessed before, during, and after therapy. RESULTS: Significant improvement
      at Day 1 after the first infusion lasting until Week 12 was reported by 5/6
      patients. Improvement of > or = 50% in all activity, function, pain, and swollen
      joint scores was observed in the patients taking 5 mg/kg. The 3 mg/kg dose was
      less effective, resulting in > or = 15% improvement in outcome variables.
      Peripheral arthritis, enthesitis, and spinal symptoms improved equally. C
      reactive protein dropped in 4 patients. Health related quality of life increased.
      No serious side effects or infections occurred. CONCLUSION: These observations
      suggest that anti-TNF-alpha therapy has significant short term efficacy in
      patients with severe uSpA.

PMID- 11824948
TI  - Evidence for synovitis in active polymyalgia rheumatica: sonographic study in a
      large series of patients.
AB  - OBJECTIVE: To determine the frequency and localization of synovitis and
      enthesitis in patients with active, untreated polymyalgia rheumatica (PMR) by
      ultrasonography (US). METHODS: Polyarticular sonographic evaluation was carried
      out in 50 consecutive patients with PMR at disease onset. Results were compared
      with 50 consecutive patients with seronegative spondyloarthropathies (SpA) and 50
      with seronegative and seropositive rheumatoid arthritis (RA) at disease onset.
      RESULTS: Synovitis and/or effusion was detected, in at least one joint, in 100%
      of patients with PMR. The most frequent alterations observed in patients with PMR
      were effusion in the subacromial-subdeltoid (SA-SD) bursa in 70% of patients,
      tenosynovitis of the long head of the biceps tendon (LHBT) in 68%, glenohumeral
      joint effusion in 66%, tenosynovitis of the flexor tendons in the carpal tunnel
      in 38%, radiocarpal effusion in 18%, wrist extensors tenosynovitis in 18%,
      coxofemoral joint effusion in 40%. knee effusion in 38%, and ankle effusion in
      10%. Enthesitis and tendonitis of the anchoring tendons were relatively rare in
      all the articular sites. Comparison of the SpA and PMR patients showed that
      enthesitis (mostly in the elbow, knee, and heel) was significantly more frequent
      in SpA. There was a significant difference in glenohumeral and coxofemoral
      effusion between the PMR and SpA patients (66% vs 16% and 40% vs 14%,
      respectively). Comparison of PMR and RA patients showed no significant difference
      in the involvement of entheses, shoulder, hip, or wrist flexor tendons in the
      carpal tunnel. Synovitis of the elbow, knee, and wrist was significantly more
      frequent in the SpA and RA patients than in those with PMR. CONCLUSION: Synovitis
      was detected in at least one site in 100% of patients with PMR. SA-SD bursitis,
      LHBT tenosynovitis, carpal tunnel syndrome, and glenohumeral, knee and hip
      synovitis were the most frequent alterations in PMR. Enthesitis was relatively
      rare at any articular site.

PMID- 11824949
TI  - Minimal clinically important rehabilitation effects in patients with
      osteoarthritis of the lower extremities.
AB  - OBJECTIVE: To estimate minimal clinically important differences (MCID) of effects
      measured by the Western Ontario and McMaster Universities Osteoarthritis Index
      (WOMAC) in patients with osteoarthritis (OA) of the lower extremities undergoing
      a comprehensive inpatient rehabilitation intervention. METHODS: A prospective
      cohort study assessed patients' health by the WOMAC at baseline (entry into the
      clinic) and at the 3 month followup, and by a transition questionnaire asking
      about the change of "health in general related to the OA joint" during that time
      period. The WOMAC section score differences between the "equal" group and the
      "slightly better" and "slightly worse" groups resulted in the MCID for
      improvement and for worsening. RESULTS: In total 192 patients were followed up.
      The MCID for improvement ranged from 0.80 to 1.01 points on the continuous WOMAC
      numerical rating scale from 0 to 10, reflecting changes of 17 to 22% of baseline
      scores. The MCID for worsening conditions ranged from 0.29 (6%) to 1.03 points
      (22%). In the transition reply subjectively unchanged patients reported a
      "pessimistic bias" of 0.35 to 0.51 points, except for the stiffness section. Both
      MCID and pessimistic bias showed regression to the mean and baseline dependency.
      CONCLUSION: The assessment of MCID using the transition method is a heuristic and
      valid strategy to detect particular rehabilitation effects in patients with OA of
      the lower extremities with the use of the WOMAC, and it is worth implementing.
      The size of the MCID and of the systematic bias is comparable to that assessed by
      other methods and in other therapeutic settings.

PMID- 11824950
TI  - The longterm outcome of osteoarthritis: rates and predictors of joint space
      narrowing in symptomatic patients with knee osteoarthritis.
AB  - OBJECTIVE: To determine the rate of progression of radiographic joint space
      narrowing (JSN) and the factors that predict it in symptomatic clinic patients
      with knee osteoarthritis (OA). METHODS: In total 1,507 patients with knee OA were
      studied with extended weight-bearing anterior-posterior views of the knee as part
      of a longitudinal study of longterm outcomes of osteoarthritis (OA). Baseline
      demographic and severity measurements included body mass index (BMI), pain,
      global severity, Health Assessment Questionnaire disability, and erythrocyte
      sedimentation rate. Rates and predictors of progression were obtained by Kaplan
      Meier survival analyses and Cox regressions using a JSN score of 3 as "failure."
      RESULTS: For the 1,232 patients who had not reached the endpoint narrowing score
      of 3 when first evaluated, the 75th and 50th survival times (time to JSN = 3)
      were 11.27 and 17.84 years for those with JSN = 0 at onset, 7.41 and 12.03 years
      for those with JSN = 1 at onset, and 4.49 and 7.44 years for those with JSN = 2
      at onset. The corresponding yearly incidence rates for the 3 initial groups were
      0.017, 0.032, and 0.077. In multivariate Cox models, initial JSN, BMI, symptom
      duration, and global severity were predictors of progression, but only JSN was a
      strong predictor. BMI predicted JSN in those with JSN = 0 at onset, but not in
      patients with more severe disease. Although contralateral JSN predicted
      progression, it was only of value with initial homolateral JSN scores of 0.
      Assessment of homolateral osteophytes aided prediction in patients with initial
      JSN = 0, but was of much less help when JSN had a higher severity score.
      CONCLUSION: The risk of progression in clinical OA patients with radiographic
      abnormalities is substantial. Nonradiographic predictors of OA progression (e.g.,
      BMI) are weak predictors of radiographic progression compared to current
      radiographic status. Rates of progression are greatest in those with established
      radiographic abnormalities. Osteophytes are of limited additional values once JSN
      = 2 is present. Contralateral radiographic abnormalities are useful predictors
      only in those with JSN = 0. Intervention studies to prevent radiographic
      progression probably should utilize joints where evidence of abnormality already
      exists. At a clinical level, current radiographic status predicts future status,
      with 50% of patients with JSN = 1 and 50% of patients with JSN = 2 progressing to
      complete joint space loss in 12.03 and 7.44 years, respectively.

PMID- 11824951
TI  - A cartilage derived novel compound DDP (2,6-dimethyldifuro-8-pyrone): isolation,
      purification, and identification.
AB  - OBJECTIVE: Fluorescent biomolecules within cartilage matrix can be used as
      specific markers of cartilage metabolism. While establishing the protocol to
      evaluate mature collagen crosslinks in articular cartilage (AC) associated with
      maturation, aging, and osteoarthritis, chromatographic analysis of the crosslinks
      also revealed an apparently novel fluorescent peak. Preliminary investigation of
      this compound (now abbreviated DDP) in various tissues from rabbits, calves,
      chickens, and humans showed that this compound is AC-specific. We aimed to
      isolate, purify, and identify this fluorescent compound. METHODS: Fully
      encapsulated, bovine metacarpophalangeal joints (n = 350, age < 2 years) were
      used as the source for AC. DDP was isolated and purified by reverse phase high
      pressure liquid chromatography, and its elution was monitored using a
      fluorescence detector at excitation lambda = 306 nm, and emission lambda = 395
      nm. The liquid phase of DDP was characterized by mass spectrometry and nuclear
      magnetic resonance spectroscopy. DDP solution (5.7 microg/microl) was
      crystallized in 100% deuterated methanol and the DDP crystal was characterized by
      single crystal x-ray diffraction. RESULTS: From bulk preparations, 12 pg (58
      nmol) per gram dried AC of the novel compound was isolated and purified.
      Analytical techniques to identify this AC-specific compound, 2,6-dimethyldifuro-8
      pyrone, corroborate and confirm its molecular structure and atomic connectivity
      in both liquid and solid phase. DDP is a symmetrical aromatic compound with
      molecular weight 204, molecular forrmula C11H8O4, and a molar extinction
      coefficient 4,700 M(-1) at maximal UV absorption (lambda = 306 nm). CONCLUSION:
      2,6-dimethyldifuro-8-pyrone (DDP) is a novel cartilage-specific compound that
      could have potential application as a unique biochemical marker in joint diseases
      involving articular cartilage degradation.

PMID- 11824952
TI  - Collagenase-1 (MMP-1) and HLA-DRB1 gene polymorphisms in rheumatoid arthritis: a
      prospective longitudinal study.
AB  - OBJECTIVE: Rheumatoid arthritis (RA) is characterized by chronic synovitis
      leading to permanent damage of the joints. Collagenase-1 (MMP-1) is a matrix
      metalloproteinase involved in articular cartilage degradation. We investigated
      the association between a biallelic polymorphism in the MMP-1 gene promoter and
      the susceptibility to, and severity of, RA. We also investigated the association
      between HLA-DRB1 gene polymorphism and severity of RA. METHODS: One hundred and
      three patients with early RA were included in this prospective longitudinal
      study. A radiographic damage score was used to quantify disease severity at
      baseline and after 4 years of followup. MMP-1 polymorphism genotyping was
      analyzed using a fluorescent-based polymerase chain reaction (PCR). HLA-DRB1
      genotypes were determined by PCR sequence-specific oligonucleotide probes. One
      hundred and thirty-three healthy individuals were used as controls. RESULTS: MMP
      1 allele and genotype frequencies did not differ between RA patients and
      controls. The radiographic damage or its progression over the 4 years of followup
      did not differ across MMP-1 genotypes. The radiographic damage score and its
      progression over the 4 years of followup differed across HLA-DRB1 genotypes. The
      HLA-DRB I shared epitope +/+ genotype was associated with the highest
      radiographic damage score and the highest progression, while the shared epitope 
      /- genotype was associated with the lowest. CONCLUSION: Our results do not
      support the hypothesis of an association between this particular polymorphism in
      the MMP-1 gene promoter and susceptibility to, or severity of, RA. This study
      confirms the previous reports of an association between the HLA-DRB1 gene
      polymorphism and severity of RA.

PMID- 11824953
TI  - Novel fluorescent compound (DDP) in calf, rabbit, and human articular cartilage
      and synovial fluid.
AB  - OBJECTIVE: To investigate the presence of and quantify 2,6-dimethyldifuro-8
      pyrone (DDP), a novel fluorescent compound identified as in various calf, rabbit,
      and human tissue/fluid samples, to determine the DDP level in articular cartilage
      (AC) laminae, and to investigate the changes in cartilage DDP content with
      cartilage maturation. METHODS: Samples were obtained from calf (< 2 years),
      rabbit (< 2 weeks to 2 years) or human AC and synovial fluid (SF) as well as
      other non-cartilaginous tissues. SF and tissue samples were hydrolyzed with 6 M
      HCl (24 hours at 110 degrees C), lyophilized, and dissolved in HPLC mobile phase.
      DDP and collagen crosslink peaks were measured using a fluorescence detector at
      excitation and emission wavelengths of 295 and 395 nm, respectively. RESULTS: DDP
      was detected from calf metacarpophalangeal joint AC (362 +/- 48 pmol/mg dry
      weight), SF (4.5 +/- 0.3 pmol/microl SF), and intervertebral disc (24 +/- 4
      pmol/mg). DDP was not detected in calf ligament, tendon, bone, ocular lens,
      cornea, or elastic cartilage. The DDP amount was greater in mid-deep cartilage
      lamina (448 +/- 63 pmol/mg) than superficial-mid lamina (129 +/- 52 pmol/mg) (p =
      0.008). DDP level decreased with maturation in rabbit knee joint AC from 185 +/-
      40 (< 2 weeks) to 27 +/- 3 (2 years) pmol/mg dry weight. DDP was not detected in
      adult rabbit ligament, tendon, meniscus, or bone. DDP was detected in human knee
      joint AC and SF. The DDP level in osteoarthritic lesions was present in lower
      concentrations (range: 0 to 96 pmol/mg dried AC) compared to intact AC (range: 63
      to 236 pmol/mg) of the same knee. CONCLUSION: DDP is a hyaline cartilage specific
      compound present in all articular cartilage samples from various articulating
      joints/animal species. DDP level increases with AC depth and decreases with
      cartilage maturation. DDP is a potential indicator of cartilage metabolism during
      normal growth, ageing, and cartilage disease.

PMID- 11824954
TI  - Absence of linkage or association for osteoarthritis with the vitamin D
      receptor/type II collagen locus: the Framingham Osteoarthritis Study.
AB  - OBJECTIVE: Studies have suggested that polymorphisms or mutations either in the
      COL2A1 or VDR gene. both on chromosome 12q, are associated with the occurrence of
      osteoarthritis (OA). We examined linkage and association between the VDR/COL2A1
      locus and hand/knee OA in the Framingham Osteoarthritis Study (FOS). METHODS:
      Hand and knee joints were characterized radiographically in the FOS. An overall
      score for OA using the standard Kellgren and Lawrence grading scheme was
      determined, as well as scores for individual features of OA including osteophytes
      and joint space narrowing. For linkage studies, polymorphic microsatellite
      markers near the VDR-COL2AI genes on chromosome 12 were tested in a collection of
      296 of the largest Framingham Heart Study families and the results analyzed using
      variance component linkage (SOLAR). For association studies, we characterized the
      allele status of a subset of subjects at the BsmI site of the VDR gene. RESULTS:
      Overall, we found no linkage or association between OA and the COL2A1/VDR locus
      for either knee or hand OA, nor did we find an association or linkage between
      COL2AI or VDR with any individual radiographic features of OA. CONCLUSION:
      Despite studies suggesting associations of OA with both COL2A1 and VDR loci, our
      results suggest that mutations at the COL2A1/VDR locus do not play an important
      role as a cause of common OA in the population at large.

PMID- 11824956
TI  - Sleep and its relationship to pain, dysfunction, and disease activity in juvenile
      rheumatoid arthritis.
AB  - OBJECTIVE: To determine what sleep abnormalities may exist in children with
      juvenile rheumatoid arthritis (JRA). and their relationship to pain, dysfunction.
      and disease activity. METHODS: Twenty-five children with active JRA (11
      pauciarticular, 9 polyarticular, 5 systemic) had their sleep assessed by
      parallel, validated patient and parent questionnaires (Sleep Self-Report, SSR,
      and Children's Sleep Habits Questionnaire, CSHQ). Disease activity was assessed
      by parent and physician global assessments (on a 5 point scale: 0 = no disease
      activity to 4 = very severe disease), erythrocyte sedimentation rate (ESR), and
      numbers of swollen and limited joints. Functional assessment was based on
      parental completion of the Juvenile Arthritis Functional Assessment Report
      (JAFAR). Pain was assessed by the average pain visual analog scale of the Varni
      Pediatric Pain Questionnaire. Results were compared to those from 45 healthy age
      and sex matched controls by Mann-Whitney U tests, and correlated with variables
      of JRA disease activity, function, and pain using Spearman correlations. RESULTS:
      Patients with JRA had higher total score on the CSHQ (p < 0.0001), as well as
      subscales assessing night wakings, parasomnias. sleep anxiety, sleep-disordered
      breathing, and morning wakening/daytime sleepiness (p < 0.0001-0.05). There were
      no correlations between CSHQ scores and JRA disease activity or pain variables,
      but the total score on the SSR did correlate with pain (r = 0.56, p = 0.005).
      CONCLUSION: We conclude that sleep abnormalities are common in children with JRA,
      and are multi-dimensional.

PMID- 11824955
TI  - Lack of association between juvenile idiopathic arthritis and fas gene
      polymorphism.
AB  - OBJECTIVE: Juvenile idiopathic arthritis (JIA) is a complex genetic disease of
      autoimmune etiology. Fas is a molecule with a pivotal role in apoptosis and hence
      in immune regulation. Elevated transcriptional levels of Fas in the synovial
      fluid of patients with JIA suggest that it might be implicated in disease
      etiopathogenesis. We investigated whether a polymorphism in the Fas promoter
      region (-670) confers susceptibility to JIA. METHODS: In this association study,
      342 UK patients with JIA and 255 healthy individuals were genotyped for the
      polymorphism using polymerase chain reaction restriction fragment length
      polymorphism. Comparisons of the genotypic frequencies were made using chi-square
      analysis. RESULTS: No statistically significant differences were found when the
      genotype frequencies of the -670 Fas polymorphism were compared between the JIA
      cases and the control panel. Similarly, no differences were seen between the JIA
      subgroups, or when the patients were divided on the basis of rheumatoid factor or
      antinuclear antibody positivity. CONCLUSION: The -670 polymorphism of Fas does
      not appear to be associated with susceptibility to JIA.

PMID- 11824957
TI  - A prospective population based study on outcome of juvenile chronic arthritis in
      Costa Rica.
AB  - OBJECTIVE: To study the disease process and outcome in an unselected group of
      patients with juvenile chronic arthritis (JCA). METHODS: From a population based
      study in San Jose, Costa Rica, 47 patients with JCA with disease onset from 1993
      through 1995 were investigated after median duration of 4.1 yrs (range 2.9-4.9)
      (incidence group). Another 49 children with disease onset prior to 1993 and
      younger than 16 years of age on December 31, 1995 (cross sectional group) were
      also followed. RESULTS: In the incidence group, 4/47 children changed subtype
      during the course of the disease. All did so within 2 years from disease onset,
      and the same observation was made in the cross sectional group. Uveitis was
      described at onset in a single case, and no child developed uveitis later. In
      patients from the incidence group in the process of being transferred to adult
      rheumatology clinics, 48% were still taking medication. Patients who had
      involvement of proximal interphalangeal (PIP) joints at onset had an increased
      risk of being active or stable at followup (RR 12.3, 95% CI 1.4-108.3). A higher
      chance of no continuing disease activity at followup was observed in children
      with oligoarticular disease than in the other subtypes (RR 2.8, 95% CI 1.2-6.9).
      CONCLUSION: Uveitis associated with antinuclear antibody positive JCA and
      psoriatic arthritis in Costa Rican children is uncommon, and the risk of
      developing uveitis remains low during the course of the disease. Involvement of
      PIP joints predicts an increased risk of continuing disease. The course of JCA in
      Costa Rican children is not milder than in Caucasian populations, since 48% of
      the patients showed persistent disease activity at the transition to adult care.

PMID- 11824958
TI  - Rheumatic manifestations of Bartonella infection in 2 children.
AB  - We describe 2 patients with very unusual rheumatological presentations presumably
      caused by Bartonella infection: one had myositis of proximal thigh muscles
      bilaterally, and the other had arthritis and skin nodules. Both patients had very
      high levels of antibody to Bartonella that decreased in association with clinical
      improvement. Bartonella infection should be considered in the differential
      diagnosis of unusual myositis or arthritis in children.

PMID- 11824959
TI  - Neonatal lupus manifests as isolated neutropenia and mildly abnormal liver
      functions.
AB  - Neonatal lupus is characterized by typical clinical features and the presence of
      maternal autoantibodies. Mothers can have systemic lupus erythematosus (SLE) or
      Sjogren's syndrome, but are commonly not affected with any clinical disease. The
      major clinical manifestations in the infants are cardiac, dermatological and
      hepatic with rare instances of hemolytic anemia, thrombocytopenia or neutropenia.
      We describe an infant born to a mother with anti-Ro and anti-La, who had
      neutropenia and mildly abnormal liver functions without other major clinical
      features of neonatal lupus such as cardiac or dermatological manifestations.
      Neutropenia improved as maternal antibody was metabolized. Antibodies from both
      the infant and mother bound intact neutrophils, and this binding was inhibited by
      60 kDa Ro. These data imply neutropenia may be an isolated manifestation of
      neonatal lupus. We studied the anti-Ro antibodies of 2 other mothers who gave
      birth to infants with complete congenital heart block and neutropenia. Their sera
      also bound neutrophils. Because healthy infants do not commonly undergo complete
      blood counts, the incidence of neutropenia among infants of anti-Ro-positive
      mothers may be much higher than previously recognized. Furthermore, although
      other factors may contribute, these data suggest that anti-60 kDa Ro is directly
      involved in the pathogenesis of neutropenia.

PMID- 11824960
TI  - Leflunomide induced fevers, thrombocytosis, and leukocytosis in a patient with
      relapsing polychondritis.
AB  - The most common adverse events reported with the use of leflunomide are
      hypertension, infections, alopecia, and various gastrointestinal complaints. No
      fatal adverse hematologic events have been reported in humans, although anemia
      and leukopenia have been described in animals receiving 20 mg/kg/day. We describe
      a patient with relapsing polychondritis, in whom treatment failure with
      glucocorticoids, methotrexate, hydroxychloroquine, and azathioprine led to the
      institution of therapy with leflunomide at a maintenance dose of 20 mg/day. Two
      months after the dose of leflunomide had been increased to 30 mg daily, the
      patient developed high fevers, photophobia, thrombocytosis, and leukocytosis that
      returned to normal following treatment with cholestyramine and discontinuation of
      leflunomide. Rechallenge with leflunomide was not attempted and the syndrome did
      not recur during 14 month followup.

PMID- 11824961
TI  - Bone marrow necrosis and refractory HELLP syndrome in a patient with catastrophic
      antiphospholipid antibody syndrome.
AB  - We describe a 22-year-old woman who developed extensive and fatal bone marrow
      necrosis along with involvement of liver, lung, and central nervous system during
      pregnancy in the background of very high titers of antiphospholipid and anti
      beta2 glycoprotein antibodies. This case illustrates a rarely recognized,
      potentially fatal complication of aPL in the setting of pregnancy.

PMID- 11824962
TI  - Identity of the joint lubricant.

PMID- 11824963
TI  - Beneficial effect of being outdoors in rheumatoid arthritis.

PMID- 11824964
TI  - Monoarthritis as presenting sign of stress fracture.

PMID- 11824966
TI  - Tumor necrosis factor-alpha gene polymorphism in severe and mild-moderate
      rheumatoid arthritis.
AB  - OBJECTIVE: To examine whether severe rheumatoid arthritis (RA) carries a -238 or
      +489 tumor necrosis factor-alpha (TNF-alpha) genotype different from mild
      moderate RA. METHODS: We investigated 163 patients (66 with severe disease) and
      67 healthy blood donor controls. Genotyping was performed by polymerase chain
      reaction-restriction fragment length polymorphism. RESULTS: Patients with severe
      RA (all active disease despite disease modifying antirheumatic drug combination
      therapy) disclosed the -238 GG genotype in 100% of cases versus 92.8% of the mild
      moderates and 92.5% of controls (OR 11.7, Cl 0.6-216, p = 0.03). The +489 AA
      genotype was seen less often in patients than in controls (OR 4.2. CI 0.97-18.4,
      p = 0.045), and the contribution to this trend appeared predominant in the anti
      TNF treated subgroup. CONCLUSION: The -238 AG genotype was absent in severe RA;
      in contrast, patients with mild-moderate RA disclosed the same frequency as
      controls. Thus -238 GG homozygosity is associated with severe RA. The +489 AA
      genotype might instead protect against worse outcome in RA.

PMID- 11824965
TI  - Effects of gold on cytokine production in vitro; increase of monocyte dependent
      interleukin 10 production and decrease of interferon-gamma levels.
AB  - OBJECTIVE: To investigate the effects of gold salt on the differential production
      of proinflammatory and antiinflammatory cytokines in vitro. METHODS: Heparinized
      blood from 10 blood donors and 10 patients with polyarthritis was density
      separated and incubated with various concentrations of gold salt [Myocrisin gold
      sodium thiomalate (GSTM) plus phenyl mercury nitrate]. Cytokine production was
      measured after incubation for 16-20 h using an Elispot method detecting
      interleukin 10 (IL-10), IL-6, tumor necrosis factor-alpha (TNF-alpha), and
      interferon-gamma (IFN-gamma) producing cells. In addition, parallel cell culture
      supernatants were collected and analyzed by ELISA for IL-10, IL-6, TNF-alpha, IFN
      gamma, and IL-2. In some cultures phytohemagglutinin A (PHA) was added in
      predefined concentrations. RESULTS: GSTM increased the number of cells producing
      IL-6 and IL-10 in a dose dependent manner, both with and without simultaneous
      addition of PHA. These effects were seen in samples from both healthy blood
      donors and patients with polyarthritis. The increase in IL-10 production was
      inhibited when monocytes were depleted. No effects of GSTM were seen on IFN-gamma
      or TNF-alpha producing cells. Parallel supernatant cultures displayed a GSTM dose
      dependent decrease in IFN-gamma levels after mitogen stimulation, whereas no
      changes were seen in IL-6 or TNF-alpha levels. CONCLUSION: The differential
      effects of gold salt on cytokine production, with a marked stimulatory effect on
      IL- 10 and IL-6, indicate that gold salt may act as a relatively selective
      immunostimulator rather than as a general immunosuppressant.

PMID- 11824967
TI  - PPARgamma ligands as modulators of inflammatory and catabolic responses in
      arthritis. An overview.

PMID- 11824968
TI  - Expression and localization of vascular endothelial growth factor-C in rheumatoid
      arthritis synovial tissue.
AB  - OBJECTIVE: Vascular endothelial growth factor-C (VEGF-C), a member of the VEGF
      family, induces lymphangiogenesis through VEGF receptor-3 (VEGFR-3/Flt-4). We
      examined the expression and localization of VEGF-C to clarify its role in
      synovial tissues in rheumatoid arthritis (RA). METHODS: Reverse transcription
      polymerase chain reaction (RT-PCR), Western blot analysis, immunohistochemical
      staining, and in situ hybridization for VEGF-C were performed on synovial tissue
      specimens obtained from 10 patients with RA and 4 with osteoarthritis (OA). VEGFR
      3 expression was determined using Western blot analysis. RESULTS: RT-PCR analysis
      showed that VEGF-C mRNA was expressed in all RA and OA synovial tissues. Based on
      Western blot analysis, the mature form of VEGF-C was found in RA synovial
      tissues, but not in OA synovial tissues, and VEGFR-3 was detected in RA and OA
      synovial tissues. Immunohistochemical staining showed that the VEGF-C protein was
      localized in many synovial lining cells, endothelial cells, and stromal cells in
      RA synovial tissues. In OA synovial tissues, the VEGF-C protein was localized in
      synovial lining cells and endothelial cells. A large number of synovial lining
      cells and stromal cells surrounding microvessels in RA synovial tissues expressed
      VEGF-C mRNA, as determined by in situ hybridization. CONCLUSION: Mature VEGF-C
      and VEGFR-3 expression may contribute to lymphangiogenesis in RA.

PMID- 11824969
TI  - Vascular endothelial growth factors C and D and their VEGFR-2 and 3 receptors in
      blood and lymphatic vessels in healthy and arthritic synovium.
AB  - OBJECTIVE: To localize vascular endothelial growth factor C (VEGF-C) and VEGF-D
      in synovial specimens in relation to their VEGFR-2 and VEGFR-3 receptors in blood
      and lymphatic vessels. METHODS: Immunohistochemical staining and messenger RNA
      analysis from control and arthritic synovial membrane specimens. RESULTS:
      Quantitative RT-PCR disclosed that VEGF-C mRNA copy numbers were higher than VEGF
      D mRNA copy numbers in the rheumatoid arthritis (RA), osteoarthritis, and control
      patient groups studied (p < 0.01). Immunohistochemical staining localized VEGF-C
      to synovial lining cell layer, pericytes, and smooth muscle cells of blood
      vessels. The number of VEGF-C positive cells was increased in the synovial lining
      of ankylosing spondylitis (AS) and RA compared to control synovium. However, in
      contrast to control synovial lining, little if any VEGF-D was detected in AS or
      RA synovial lining. VEGFR-2 expressing stromal blood vessels, also positive for
      the vascular endothelial marker PAL-E and the basement membrane marker laminin,
      were more abundant in RA and AS than in controls. Interestingly, the lymphatic
      endothelial receptor VEGFR-3 was also expressed in most synovial vessels,
      especially in the sublining capillaries and venules. CONCLUSION: VEGF-C is
      strongly expressed in the hypertrophic synovial lining of arthritic joints,
      whereas VEGF-D expression is very low in AS and RA. The expression of VEGF-C and
      VEGF-D in pericytes and smooth muscle cells suggests that these factors may have
      a role in maintaining vascular homeostasis. The VEGF receptors VEGFR-2 and VEGFR
      3 are present in most of the sublining blood vessels. The expression of the
      lymphatic marker VEGFR-3 in the sublining blood vessels may relate to fluid
      filtration and/or fenestrations. The relatively few lymphatic vessels along with
      increased vascular permeability in RA may contribute to the development of tissue
      edema and joint stiffness.

PMID- 11824970
TI  - Effects of dexamethasone on lymphocyte proliferation and cytokine production in
      rheumatoid arthritis.
AB  - OBJECTIVE: We evaluated the pattern of dexamethasone mediated inhibition of
      concanavalin-A (Con-A) stimulated peripheral blood mononuclear cell (PBMC)
      proliferation to classify patients with rheumatoid arthritis (RA) as
      corticosteroid resistant (CR) or sensitive (CS). We also studied the role of T
      helper 1, (Th1) and Th2 cytokines in the mechanism of glucocorticoid resistance
      in RA. METHODS: PBMC from 21 healthy controls and 15 patients with RA were
      isolated and cultured for the in vitro glucocorticoid sensitivity assay. Basal
      and Con-A stimulated PBMC proliferation levels and the inhibitory effect of
      different doses (10(-8), 10(-6), 10(-4) M) of dexamethasone (Dex) were evaluated.
      The IC50 was defined as the concentration of Dex that caused 50% inhibition of
      cell proliferation and subjects with an IC50 > 10(-6) M were considered to be CR.
      The supernatants were collected for cytokine [interleukin 4 (IL-4), IL-6, IL-10,
      tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma)]
      measurement by ELISA. RESULTS: We observed lymphocyte proliferation after Con-A
      stimulation, which was inhibited by Dex in a dose-dependent manner in both
      groups. Two of 21 controls (9.5%) and 7/15 RA patients (53.3%) were CR (p <
      0.01). Basal IL-4, IL-6, IL-10, and TNF-alpha levels were similar for both
      groups; however, basal IFN-gamma levels were slightly higher in patients with RA
      compared to controls. Con-A stimulation did not increase IL-4 or IL-6 levels
      compared to basal production but significantly increased IL-10 levels. IL-6 and
      IL-10 levels were significantly inhibited by Dex 10 M in both the control and RA
      groups. Con-A stimulation significantly increased TNF-alpha and IFN-gamma levels
      compared to the basal condition in the control and RA groups, and both cytokines
      were inhibited only by higher doses of Dex in the RA group. CONCLUSION: These
      findings might reflect a predominance of Th1 cells in RA that might contribute to
      corticosteroid resistance in patients in RA.

PMID- 11824972
TI  - Altered levels of soluble adhesion molecules in patients with rheumatoid
      arthritis complicated by peripheral neuropathy.
AB  - OBJECTIVE: To assess levels of 2 circulating soluble adhesion molecules, vascular
      cellular adhesion molecule (sVCAM) and E-selectin, in patients with rheumatoid
      arthritis (RA) complicated by peripheral neuropathy compared to RA patients with
      no neurological complications and healthy controls. METHODS: In total, 25 RA
      patients with peripheral neuropathy (detected by clinical examination and
      confirmed by electromyography and nerve conduction studies), 40 RA patients
      without peripheral neuropathy, and 25 controls were studied. Clinical and
      laboratory assessments of disease activity were carried out and levels of sVCAM-1
      and E-selectin were measured by ELISA in each of the 3 groups. RESULTS: Levels of
      sVCAM-1 and sE-selectin were higher (p < 0.001) in RA patients with peripheral
      neuropathy than in patients without neuropathy and controls. Levels of sE
      selectin and sVCAM-1 correlated positively with disease activity variables.
      Correlation was independent of age and sex. CONCLUSION: Peripheral neuropathy in
      patients with RA is associated with increased endothelial cell activation
      evidenced by elevated serum levels of sVCAM-1 and sE-selectin in this group of
      patients.

PMID- 11824971
TI  - A population based assessment of the use of orthopedic surgery in patients with
      rheumatoid arthritis.
AB  - OBJECTIVE: To describe the use of orthopedic surgery, including joint replacement
      surgery, in a well defined population based cohort of patients with rheumatoid
      arthritis (RA) and to identify characteristics that predict such use. METHODS: A
      retrospective medical record review was performed of cases of RA incident in
      Rochester, MN, during the years 1955-85. Patients were followed until 1998. All
      joint surgeries were recorded, including joint reconstructive surgeries, total
      joint arthroplasty (TJA), and other joint reconstructive procedures (JRP) such as
      tendon transfers and resections, joint fusions, and surgeries for fractures and
      infections involving joints. RESULTS: Of the total 424 RA incident cases, 148
      (34.9%) patients underwent one or more (maximum of 20/patient) surgical
      procedures involving joints during their followup (median 14.8 yrs, range 0.2
      42.8 yrs). Overall, this RA cohort had 9.7 surgeries per 100 person-yrs of
      followup. The estimated cumulative incidence of surgical procedures for RA at 30
      yrs was 52.7% +/- SE 4.2. Surgeries for arthritis related joint disease of RA
      included: primary TJA 76 patients (31.3 +/- 4.1); JRP joint fusion 78 patients
      (29.4 +/- 3.5); JRP soft tissue 92 patients (29.8 +/- 3.3); and cervical spine
      fusion one patient. Non-RA (trauma and other) joint surgeries included TJA 26
      patients (13.5 +/- 3.4) and arthrotomy for septic arthritis 8 patients (2.4 +/-
      0.9). Based on Cox proportional hazards regression, the risk of having a disease
      related joint surgery for RA is increased in patients who are younger (p <
      0.001), have positive rheumatoid factor (p = 0.01), and those with rheumatoid
      nodules (p < 0.001). There was a borderline significant increase in the risk of
      first joint surgery in women (p = 0.09). Women also had significantly more joint
      surgeries (11.5/100 person-yrs) than men (4.9/100 person-yrs; p < 0.001).
      Survival of patients who had surgery for RA related joint disease was similar to
      those who did not. CONCLUSION: This is the first population based assessment of
      joint surgeries performed in patients with RA. Reconstructive surgeries were
      common, and women had significantly more surgeries than men. Survivorship among
      patients with RA undergoing surgeries was similar to that of the RA patient
      population at large.

PMID- 11824973
TI  - Occurrence of extraarticular disease manifestations is associated with excess
      mortality in a community based cohort of patients with rheumatoid arthritis.
AB  - OBJECTIVE: To investigate the occurrence of extraarticular manifestations (ExRA)
      in a well defined community based cohort of patients with rheumatoid arthritis
      (RA), and to examine their effect on mortality. METHODS: Using the resources of
      the Rochester Epidemiology Project, a retrospective medical record review was
      conducted of a cohort of 424 cases of RA in Olmsted County, MN, USA, diagnosed
      during the period 1955-1985. These cases had been classified using the American
      College of Rheumatology 1987 criteria for RA. Patients were followed 1955-1998
      (median followup 14.8 yrs; range 0.2-42.8 yrs), and incident ExRA manifestations
      were recorded according to predefined criteria. Data on comorbidities were
      extracted using the definitions of the Charlson comorbidity index. Survival was
      compared to the general population using Kaplan-Meier estimates. RESULTS: ExRA
      occurred in 169 patients, corresponding to an incidence rate of 3.67/100 person
      yrs. Compared to the general population, survival among patients with RA was
      decreased. Survival among patients with ExRA was markedly decreased compared to
      the general population and to patients without ExRA (p < 0.001). A particularly
      poor prognosis was noted in a subgroup of 63 patients (incidence rate 1.04/100
      person-yrs) who fulfilled predefined criteria for severe ExRA (i.e., vasculitis,
      pericarditis, pleuritis, and/or Felty's syndrome). For RA patients who did not
      fulfill these criteria, there was no significant increase of mortality (p =
      0.09). In a multivariate model of mortality, including age, sex, and the presence
      of known comorbidities, the presence of one or more of these ExRA was the
      strongest predictor of mortality. CONCLUSION: In this first community based study
      of extraarticular manifestations in RA, virtually all the excess mortality
      occurred in a subgroup of patients with severe extraarticular disease, suggesting
      that extraarticular disease is the major predictor of mortality in patients with
      RA.

PMID- 11824974
TI  - A critical evaluation of enzyme immunoassay kits for detection of antinuclear
      autoantibodies of defined specificities. II. Potential for quantitation of
      antibody content.
AB  - OBJECTIVE: To analyze the performance of different commercial enzyme immunoassay
      (EIA) kits for measuring antibody levels of antinuclear antibodies (ANA) specific
      for double stranded (ds) DNA, SSB/La, Sm, and Scl-70. METHODS: Twenty companies
      that were known major purveyors of EIA kits for detection of ANA were approached
      to determine their interest and willingness to participate in this study. The
      manufacturers were advised that they would be sent coded sera containing mixtures
      of the Arthritis Foundation/Centers for Disease Control reference reagents, and
      that they were to use their own test kits to analyze the antibody specificities
      of these sera and to report the data, in optical density (OD) units, or their
      equivalent. The analysts were blinded to the concentration of the antibodies and
      the specificities. RESULTS: Initially, 11 manufacturers out of 20 agreed to
      participate, but 2 subsequently withdrew. The commercial EIA kits have the
      potential of being able to quantitate specific autoantibody content to ds-DNA,
      SSB/La, Sm, and Scl-70. However, certain deficiencies in these kits were also
      detected, the most obvious being lack of uniformly good performance, with kits of
      certain manufacturers showing exceptional accuracy in 3 out of 4 of their
      antibody-specific kits and poor accuracy for a 4th kit. CONCLUSION: It is
      important for clinicians to appreciate that there is marked inter-manufacturer
      variation in the performance of EIA kits used as an aid in the diagnosis of
      systemic rheumatic diseases. Manufacturers need to exercise constant surveillance
      of kit performance and to provide assurance that such is being done. Improved EIA
      kits would lend themselves to reliable quantitation of antibody levels in human
      sera and help to determine whether serial measurement of antibody levels might be
      useful in monitoring disease activity.

PMID- 11824975
TI  - Treatment of severe immune thrombocytopenia associated with systemic lupus
      erythematosus: 59 cases.
AB  - OBJECTIVE: To evaluate the response to treatment in a large cohort of patients
      with systemic lupus erythematosus (SLE) associated with autoimmune
      thrombocytopenia. METHODS: Response to treatment was assessed retrospectively in
      59 patients with SLE, either definite (n = 44) or incomplete (n = 15), associated
      with frank autoimmune thrombocytopenia (defined as platelet count < 50 x
      10(9)/l). Response to treatment was classified as complete (CR: platelet count >
      150 x 10(9)/l), partial (PR: platelet count > 50 x 10/l), or failure (FR) in the
      other cases. RESULTS: Oral prednisone alone was used in 50 of the 59 patients
      (mean initial dose 1 mg/kg body weight/day). A response was obtained in 80% of
      cases (CR in 28. PR in 12) but only 11 (22%) had a sustained response (CR, n = 7;
      PR, n = 4). In contrast, combined treatment with prednisone and either danazol (n
      = 18) or hydroxychloroquine (n = 11) resulted in 50% (7 CR, 2 PR) and 64% (4 CR,
      3 PR) longterm responses, respectively, allowing prednisone to be withdrawn or
      the dose tapered below 0.2 mg/kg body weight/day. High dose methylprednisolone
      pulses (n = 10) and intravenous immunoglobulin (IVIG) (n = 31) resulted in
      positive responses in 60% (4 CR, 2 PR) and 65% (12 CR, 8 PR) of cases,
      respectively, but the response was transient in each case. Splenectomy (n = 17)
      resulted in 65% longterm responses (10 CR, 1 PR). Only 2 longterm partial
      responses were obtained with the 22 immunosuppressant-containing regimens
      administered to 14 patients. At the end of the study. a response was observed in
      52 (88%) patients [CR: 36 (61%), PR: 16 (27%)], mainly as a result of splenectomy
      or combined treatment with prednisone and either danazol or hydroxychloroquine.
      CONCLUSION: Longterm remission was obtained in the majority of patients. The
      major treatments inducing remission were splenectomy and prednisone combined with
      danazol or hydroxychloroquine.

PMID- 11824976
TI  - The effect of high salt concentration on detection of serum immune complexes and
      autoantibodies to C1q in patients with systemic lupus erythematosus.
AB  - OBJECTIVE: To compare the binding of immune complexes and anti-Clq in systemic
      lupus erythematosus (SLE) sera to Clq and to the purified collagen-like region of
      Clq (CLR) in high and physiologic NaCl concentrations. METHODS: Sera from
      patients with SLE were tested for binding of IgG to Clq and to CLR in physiologic
      (0.15 M NaCl) or high (1.0 M NaCl) salt concentration. Sera were ultracentrifuged
      to separate monomeric IgG and high molecular weight IgG (immune complexes), and
      fractions were tested for binding to C1q and to CLR in the presence of
      physiologic or high salt concentrations. RESULTS: Decrease in binding of immune
      complexes to Clq in the presence of high salt ranged from 0 to 96.8%, with a
      median of 48.4%. Decrease of the binding of monomeric IgG to C1q in the presence
      of high salt ranged from 2.2 to 74.3%, with a median of 46.2%. Binding of
      monomeric autoantibodies to CLR also was decreased by high salt. Nevertheless,
      anti-Clq measured by binding to CLR in physiologic salt correlated highly with
      the binding to Clq in both physiologic (r = 0.978) and high salt (r = 0.983).
      CONCLUSION: Clq-binding of immune complexes in SLE sera is not uniformly
      abrogated by high salt and binding of autoantibodies to CLR is variably reduced
      by high salt. Binding of IgG to Clq in high salt correlates with but is not
      equivalent to quantifying these autoantibodies by binding to CLR.

PMID- 11824977
TI  - High prevalence of autoantibodies against the nuclear high mobility group (HMG)
      protein SSRP1 in sera from patients with systemic lupus erythematosus, but not
      other rheumatic diseases.
AB  - OBJECTIVE: To evaluate the presence of autoantibodies to the high mobility group
      (HMG) structure specific recognition protein I (SSRP1) in sera from patients with
      systemic lupus erythematosus (SLE) or other rheumatic diseases. METHODS:
      Antibodies to SSRP1(anti-SSRP1) were measured in sera from patients with SLE,
      Sjogren's syndrome (SS), ulcerative colitis (UC), systemic sclerosis (SSc),
      rheumatoid arthritis (RA), and sera from healthy individuals by both an enzyme
      linked immunoassay (ELISA) and Western blotting (WB) using the recombinant SSRP1
      N-terminus as antigen. RESULTS: We found 28.8% of the sera from patients with SLE
      contained anti-SSRPI by both ELISA and WB assay, compared to 8.3% of the sera
      from healthy individuals. When the 40 sera from patients with other autoimmune
      diseases were tested, only 2 sera (5%) from individuals with SS showed a moderate
      reactivity to SSRPI in both ELISA and WB assays. CONCLUSION: The results show
      that anti-SSRPI can be identified in sera from patients with SLE, but not with
      other rheumatic diseases and may thus help the diagnosis of SLE in the presence
      of appropriate clinical findings.

PMID- 11824978
TI  - Enhanced expression of the receptor for granulocyte macrophage colony stimulating
      factor on dermal fibroblasts from scleroderma patients.
AB  - OBJECTIVE: To elucidate events that initiate the involvement and stimulation of
      fibroblasts in systemic sclerosis (SSc). METHODS: We examined 15 patients with
      SSc diffuse form, 15 with CREST syndrome, and 5 healthy subjects. Cultured
      fibroblasts obtained from skin biopsies in SSc involved and non-involved areas
      and norrmal skin fibroblasts were cultured with different doses of granulocyte
      macrophage colony stimulating factor (GM-CSF) to study the effects of this factor
      on the expression of GM-CSF receptor (GM-CSFR) on fibroblast proliferation and
      cellular adhesion structures. RESULTS: Cultured fibroblasts obtained from
      biopsies of normal and SSc skin areas express GM-CSFR and such expression is
      increased in SSc fibroblasts. GM-CSF stimulation in vitro did not increase SSc
      fibroblast growth, in spite of a strongly increased expression of the GM-CSFR.
      The adhesion structures are always more abundant in SSc fibroblasts as compared
      to healthy cells and GM-CSF seems able to increase cell adhesion plaques.
      CONCLUSION: We suggest that shift of fibroblasts toward a more adhesive
      differentiated pattern, due to or accompanied by an increased expression of GM
      CSFR, may be an important event in the pathogenesis of SSc.

PMID- 11824979
TI  - Election reflection.

PMID- 11824980
TI  - Tracing and recruiting a cohort with community acquired hepatitis 25 years later.
AB  - OBJECTIVE: We describe the methods used to trace and recruit a cohort (including
      injecting drug users) 25 years after admission to hospital in Melbourne with
      hepatitis. METHODS: Information recorded in the original medical record was used
      for tracing purposes. Subjects were located using the electoral roll, CD-ROM
      telephone directory, the Health Insurance Commission database, Hepatitis
      Foundation newsletters, advertising and features in the press and local radio.
      Other approaches included contacting local medical officer or next of kin from
      the original admission, and the National Death Registry. RESULTS: Tracing was
      undertaken on all members of the cohort; two-thirds were located. Methods were
      applied sequentially and 36% were found by CD-ROM telephone directory and the
      electoral roll, 33% from Health Insurance records, 15% by letter to last known
      address, 10% from contact of original next of kin, 3% from radio publicity and 1%
      from media advertisements. Of those who were located, 85% participated in the
      study. CONCLUSIONS: Accurate ascertainment of birth date and full name from
      original case records was essential for tracing purposes. Use of Health Insurance
      records and CD-ROM telephone directory and the electoral roll were the most
      successful means of locating subjects while newspaper advertising was non
      productive and expensive. History of IDU was the major association with failure
      to trace and unwillingness to enrol, but despite this tracing and recruitment was
      high in this group. The high participation rate in those located appears to be
      due to the experience of the staff member making the initial contact.

PMID- 11824981
TI  - Interpreting scores on the Kessler Psychological Distress Scale (K10).
AB  - OBJECTIVE: To provide normative data on the Kessler Psychological Distress Scale
      (K10), a scale that is being increasingly used for clinical and epidemiological
      purposes. METHOD: The National Survey of Mental Health And Well-Being was used to
      provide normative comparative data on symptoms, disability, service utilisation
      and diagnosis for the range of possible K10 scores. RESULTS: The K10 is related
      in predictable ways to these other measures. IMPLICATIONS: The K10 is suitable to
      assess morbidity in the population, and may be appropriate for use in clinical
      practice.

PMID- 11824982
TI  - Are men and women equally violent to intimate partners?
AB  - Violence against women is a significant public health issue. One form of violence
      against women, intimate partner abuse or domestic violence, is prevalent in
      Australia. In this article, we summarise the main theoretical and methodological
      debates informing prevalence research in this area. We explain why studies
      finding equivalent victimisation and perpetration rates between the sexes are
      conceptually and methodologically flawed and why coercion and control are
      fundamental to the definition and measurement of partner abuse. We conclude that
      while male victims of partner abuse certainly exist, male victims of other forms
      of male violence are more prevalent. A focus on gendered risk of violence in
      public health policy should target male-to-male public violence and male-to
      female intimate partner abuse.

PMID- 11824983
TI  - Opting off the New South Wales Pap Test Register in a sexual health setting.
AB  - OBJECTIVES: To determine the proportion of women having a Pap smear at Sydney
      Sexual Health Centre (SSHC) who opted off the NSW Pap Test Register (PTR) and to
      establish the characteristics of these women. DESIGN: Retrospective cross
      sectional study involving three time periods during 1996 and 1997. SETTING: A
      public sexual health centre in Sydney. PARTICIPANTS: 985 women who had a Pap
      smear at SSHC. MAIN OUTCOME MEASURES: The participant's decision to opt on or
      off, and the demographic and behavioural characteristics associated with opting
      off the PTR. RESULTS: 590 (59.9%) women opted off the PTR. Using logistic
      regression, young age (p=0.005), birth outside Australia and New Zealand
      (p=0.0001), not speaking English at home (p=0.005) and being a commercial sex
      worker (CSW) (p=0.0001) were variables associated with opting off the PTR. Women
      from countries outside of Australia and New Zealand were more likely to opt off,
      whether or not they were a CSW and CSWs were more likely to opt off the PTR
      irrespective of their country of birth (p=0.013). CONCLUSION: The majority of
      women (60%) attending the SSHC opted off the PTR. Studies to evaluate culturally
      appropriate health promotion material particularly for CSWs and women with poor
      English skills living in Australia are needed and if successful may improve
      uptake on the PTR.

PMID- 11824984
TI  - Cervical screening: population-based comparisons between self-reported survey and
      registry-derived Pap test rates.
AB  - OBJECTIVE: To compare self-reported cervical screening rates, as recorded in the
      1998 NSW Health Survey, with registry-based cervical screening rates for NSW for
      the same period; and to examine factors associated with over-estimates of
      cervical screening rates by self-report. METHODS: Self-reported cervical
      screening data was extracted from the 1998 NSW Health Survey, biennial screening
      rates estimated and compared with biennial cervical screening rates for 1997-98,
      as recorded on the NSW Pap Test Register (PTR). Rates and differences were
      related to socio-demographic characteristics of the 17 Area Health Services of
      NSW. RESULTS: According to the 1998 NSW Health Survey, 74% of women reported
      having a Pap test during the previous two years. The equivalent rate recorded on
      the NSW PTR for 1997-98 was 62% (p<0.0001). Among the 17 Area Health Services of
      NSW these differences ranged from nine to 19 percentage points. Area-specific
      differences between self-reported and registry-based screening rates were
      negatively correlated with the registry-based screening rate. Age-specific
      differences between self-reported and registry-based screening rates were
      positively correlated with registry-based screening rates. No SES, regional or
      migrant population characteristics were predictive of differences between
      recorded and surveyed screening rates. CONCLUSION: Cervical screening rates in
      NSW derived from self-reported survey data exceed the rate recorded by the NSW
      Pap Test Register by 12 percentage points (equivalent to 19% inflation).
      IMPLICATIONS: The data in this paper can be used indicatively where necessary to
      adjust for over-reporting in cervical cancer screening surveys.

PMID- 11824985
TI  - Drink and drug driving: what's the skipper up to?
AB  - OBJECTIVE: Since the introduction of random breath testing (RBT) in Australia
      there has been a significant reduction in drink driving, as measured by alcohol
      related crashes. In contrast, the prevalence of drug-related road fatalities is
      on the increase. One strategy that targets drink- and/or drug-driving is the
      promotion of a designated driver or 'skipper'. This paper determines to what
      extent the 'skipper' is driving alcohol or drug-free. METHODS: A convenience
      sample of university students from The University of Western Australia completed
      a questionnaire that included questions on drug and alcohol use while driving as
      the designated 'skipper'. RESULTS: The mean age of the 286 participants was 21
      years. Among the students who reported acting as the designated 'skipper' during
      the past 12 months, 26% of the students drove, as the designated 'skipper,' while
      feeling the effects of alcohol. Similarly, 18% of students who reported using
      drugs drove, as the 'skipper', while feeling the effects of the drug.
      Multivariate analysis identified that the presence of random drug testing would
      act as a deterrent for drug driving while the designated 'skipper'. CONCLUSION:
      Although three-quarters of designated 'skippers' do not drink and/or drug drive,
      a sizeable proportion of young drivers continue to place themselves and, more
      importantly, their passengers and the entire community at an elevated risk of
      injury. IMPLICATIONS: Campaigns that target the responsibility of the 'skipper'
      and that are included as part of drink-driving campaigns would be beneficial. It
      is premature to be making recommendations on random drug testing for drivers.

PMID- 11824986
TI  - February asthma outbreaks in NSW: a case control study.
AB  - OBJECTIVES: To investigate individual factors associated with an asthma outbreak
      among children aged one to 14 years in Sydney in February 1999. METHODS: A case
      control study was undertaken with cases (n=92) defined as all children admitted
      to Sydney Children's Hospital for asthma in February 1999. Unmatched controls
      (n=76) were all children admitted for asthma in the previous three months. We
      obtained information by a structured telephone survey of parents. Logistic
      regression analyses were used to determine odds ratios for risk factors for
      hospital admission. RESULTS: Mean age for hospital admission of 4.7 years for
      cases and 4.4 years for controls. The presence of one or more siblings reduced
      the risk of admission during an asthma outbreak (OR=0.59, 95% CI 0.37 to 0.93).
      Children with older siblings aged 10 to 14 years were also less likely to be
      admitted (OR=0.3, 95% CI 0.12 to 0.74). An age effect was observed. Other
      demographic, clinical and environmental characteristics, including smoking, were
      not associated with admission during the outbreak. CONCLUSIONS: The main findings
      of this study are the protective effect of siblings and an age-dependent effect
      in risk of hospital admission during an asthma outbreak. These findings are
      consistent with an infective cause of the outbreak. IMPLICATIONS: Children
      without siblings, particularly older siblings, appear to be at highest risk of
      hospital admission during an asthma outbreak. Environmental and other factors
      need to be examined to further explain the episodicity of such outbreaks and to
      determine means of predicting and preventing future episodes.

PMID- 11824987
TI  - Adolescents' perceptions of a health survey using multimedia computer-assisted
      self-administered interview.
AB  - OBJECTIVE: To ascertain young people's perceptions of an adolescent health survey
      when administered by multimedia computer assisted self-administered Interview (M
      CASI) through analysis of (1) questionnaire item responses and (2) focus group
      interviews. METHODOLOGY:  SETTING: Auckland, New Zealand, 1999. STUDY TYPE: Pilot
      testing of a 488-item branching questionnaire delivered using a youth-oriented
      and user-friendly M-CASI interface in a variety of settings using both desktop
      and laptop computers. Post pilot focus groups of participants identifying their
      perceptions and experiences of the survey. SAMPLE: 110 school students aged 12 to
      18 years. RESULTS: The mean number of questions answered by participants was 316
      with the median time to completion being 48 minutes. On average 65% of the total
      number of questions were seen and of these 1.5% were deliberately not answered. A
      high level of acceptability and enjoyment of M-CASI was found in the analysis of
      focus group responses and agreed with the item responses relating to M-CASI
      within the questionnaire itself. Participants identified privacy and
      confidentiality as being particularly important for the honesty of their
      responses. The passive matrix screens of the computers were popular as they could
      only be viewed from in front. CONCLUSIONS: M-CASI is an acceptable instrument for
      the administration of a youth health survey. Laptop computers with passive matrix
      screens are able to enhance perceptions of privacy and confidentiality, which may
      improve honesty of responses. IMPLICATIONS: M-CASI is now feasible and offers
      advantages in health surveying.

PMID- 11824988
TI  - Recognising and responding to outbreaks of hepatitis A associated with child day
      care centres.
AB  - OBJECTIVES: To assess the appropriateness of a protocol for recognising and
      responding to outbreaks of hepatitis A in child day-care centres and to determine
      if measles-mumps-rubella (MMR) vaccine was given too soon following the
      administration of normal human immunoglobulin (NIGH) to young children to control
      the outbreaks. DESIGN: Prospective surveillance to recognise cases of hepatitis A
      associated with, and outbreaks of hepatitis A in, day-care centres. MAIN OUTCOME
      MEASURES: The percentage of initial ('sentinel') cases of hepatitis A associated
      with day-care centres that were subsequently recognised as also being 'index'
      cases of outbreaks of hepatitis A in the centres, and the number of children 9-13
      months of age when given NIGH who were subsequently given MMR less than three
      months later. RESULTS: Only 18 (16%) of the 114 sentinel day-care associated
      cases of hepatitis A were also index cases of outbreaks of hepatitis A in their
      respective centres. A total of 105 cases of hepatitis A were associated with the
      18 outbreak centres; NIGH was administered to 928 (78%) of the attendee children,
      and to 105 (82%) of the susceptible staff, at the 18 centres. Three of the five
      children 9-13 months of age when given NIGH were given MMR less that three months
      later. CONCLUSIONS: Although outbreaks of hepatitis A were common events in day
      care centres in north Queensland during the two-year study period, a single case
      of hepatitis A associated with a centre was a poor predictor of an outbreak
      within that centre. Precautions must be taken to ensure that live vaccines are
      not administered to young children too soon after NIGH.

PMID- 11824989
TI  - A serosurvey evaluation of the school-based measles 'catch-up' immunisation
      campaign in Victorian school-aged children.
AB  - OBJECTIVE: To determine the proportion of Victorian primary school students
      protected against measles infection one year after the completion of the measles
      'catch-up' immunisation campaign of 1998 and to compare this with the proportion
      of year 9 and 10 (aged 14-16 years) students. DESIGN & SETTING: Three-stage
      random cluster survey in Victorian primary and secondary schools. MAIN OUTCOME
      MEASURES: Proportion of primary and year 9 and 10 secondary school students
      protected against measles infection one year after the completion of the mass
      'catch-up' immunisation campaign. SECONDARY OUTCOMES: the proportion of both
      primary and year 9 and 10 secondary school students protected against both mumps
      and rubella. RESULTS: Of 1,037 Victorian primary and 2,357 years 9 and 10
      secondary school students invited to participate in this study, 403 (39%) and 752
      (32%) respectively provided a blood specimen for serological testing for
      antibodies against measles, mumps and rubella. 94.8% (95% confidence interval,
      91.5, 96.9) of primary school and 93.1% (90.9, 94.8) of year 9 and 10 students
      were protected against measles infection. CONCLUSION: One year after the
      completion of the school-based measles 'catch-up' immunisation campaign the level
      of protection in Victorian primary school aged students is sufficient to prevent
      the continuing circulation of measles virus within this age group. The proportion
      of year 9 and 10 secondary school students protected against measles is also
      probably sufficient to prevent continuing circulation of wild type virus in
      Victoria, even though this age group was not specifically targeted by the 'catch
      up' campaign.

PMID- 11824990
TI  - School immunisation certificates--a review over time in a disadvantaged
      community.
AB  - OBJECTIVES: To compare proportions of kindergarten children in Auburn presenting
      School Immunisation Certificates (SIC) or other school-entry immunisation
      documentation over time, and to examine the immunisation status of these
      children. METHODS: Immunisation records of kindergarten children enrolled in all
      primary schools in the Auburn local government area were reviewed in 1994 and
      1998. RESULTS: Eight hundred and thirty-three and 737 school entry records of
      children enrolled in kindergarten were reviewed in 1998 and 1994 respectively.
      There was no change in the overall proportion of children with immunisation
      documentation and SICs. Sixty-nine per cent (571/833) of children had SICs in
      1998, compared with 72% (531/737) in 1994. Thirteen per cent of children had
      other immunisation documentation in 1998, compared with 11% in 1994. The
      proportion of invalid certificates fell from 39.2% in 1994 to 12.6% in 1998
      (p<0.001). The 1998 survey indicated that 80.2% of children provided a
      certificate indicating they were completely immunised compared with 56.7% in 1994
      (p<0.001). IMPLICATIONS: Although SICs play an important role in promoting the
      importance of immunisation among parents and in the school community, there
      continues to be a substantial number of children whose immunisation status is
      unknown. In the event of an outbreak, an effective public health response may
      need to incorporate the use of additional objective measures, such as the
      Australian Childhood Immunisation Register or personal health records.

PMID- 11824991
TI  - An evidence-based review of current guidelines for the public health control of
      typhoid in Australia: a case for simplification and resource savings.
AB  - BACKGROUND: Although an uncommon disease in Australia, public health control
      measures for typhoid remain important to prevent further cases, however, they are
      labour intensive. METHODS: We reviewed current guidelines from all Australian
      states and territories, England and the United States to ascertain whether
      recommended control measures for typhoid are supported by evidence from the
      medical literature or data from Victorian typhoid notifications. RESULTS:
      Guidelines lacked consistency and were overly complex, particularly with
      reference to the frequency and timing of faecal specimens required to demonstrate
      eradication of typhoid from cases and contacts. Data from the medical literature
      are limited and do not support the superiority of any one approach, or multiple
      approaches based on risk groups of cases or contacts. Victorian data suggest that
      a general approach, with a reduction in the number of specimens collected and
      duration of follow-up is reasonable. CONCLUSIONS: Potential exists for
      simplification and improved consistency between guidelines for the public health
      control of typhoid, with associated resource savings.

PMID- 11824992
TI  - The initial coverage and impact of the pneumococcal and influenza vaccination
      program for at-risk indigenous adults in Far North Queensland.
AB  - OBJECTIVES: To describe the initial coverage and impact of a pneumococcal and
      influenza vaccination program for at-risk Indigenous adults in Far North
      Queensland that formally commenced in 1996. DESIGN: Ascertainment of vaccine
      coverages, and prospective laboratory surveillance of invasive pneumococcal
      disease occurring in Indigenous adults in the region. MAIN OUTCOME MEASURES:
      Coverages of the first doses of both vaccines administered since 1995, and the
      incidence of invasive pneumococcal disease in Indigenous adults in the region
      between 1993-2000. RESULTS: Most (96% and 73%) of the Indigenous adults > or = 50
      years of age received influenza and pneumococcal vaccines, respectively, for the
      first time between 1995-2000. Assuming that either 33% or 50% of Indigenous
      adults 15-49 years of age in Far North Queensland were eligible for vaccination,
      then either 109% or 72% of this population received influenza vaccine, and either
      75% or 50% received pneumococcal vaccine, respectively, for the first time
      between 1995-2000. The incidence of vaccine-preventable invasive pneumococcal
      disease fell from 111 (95% confidence interval [CI] 77-154) cases per 100,000 per
      year in 1993/94 to 28 (95% CI 13-53) cases per 100,000 per year in 1999-2000
      (p<0.05). CONCLUSION: Although there was a significant decline in the incidence
      of invasive pneumococcal disease, the vaccine coverages after five years of the
      program were suboptimal. Because of the difficulties in targeting the 15-49 years
      age group and because of unrecognised risk factors, we suggest that a universal
      Indigenous adult pneumococcal and influenza vaccination program should be
      considered.

PMID- 11824993
TI  - Evaluating the efficacy of vaccine storage in the general practice setting.
AB  - OBJECTIVES: To describe the implementation of guidelines for vaccine storage in
      general practice, and their effectiveness in achieving optimum vaccine storage
      temperatures in fridges. DESIGN: Repeated cross-sectional surveys over time-
      phase 1 1996/97, phase 2 1998/99, phase 3 1999/2000. SETTING: Central Coast, New
      South Wales. PARTICIPANTS: Phase 1--all general practices on the Central Coast.
      Phases 2 and 3--samples of practices. INTERVENTIONS: Each practice was surveyed
      about how they stored vaccines. A datalogger recorded fridge temperatures over
      six days. Individual feedback and advice were given. MAIN OUTCOME MEASURES:
      Proportion of: 1. fridges maintaining a temperature in the 2-8 degrees C range;
      2. fridges freezing; 3. practices with one person responsible for vaccine
      storage; 4. bridge temperature checked daily; 5. fridges storing no items other
      than vaccines; 6. bridges with thermometers; and 7. associations between storage
      practices and fridge temperatures. RESULTS: In phase 1, 102 fridges, and in phase
      3, a random sample of 36 practices was surveyed. The findings for phase 1 and
      phase 3 respectively were: 31% and 50% of fridges were in the 2-8 degrees C
      range; 36% and 25% were <0 degrees C; one person was responsible in 52% and 53%
      of cases; 20% and 38% reported daily checks; 74% and 94% of fridges had no
      extraneous items and 53% and 86% of fridges had thermometers. No statistically
      significant associations were found between vaccine storage practices and bridge
      temperatures. CONCLUSIONS: Despite improvements in vaccine storage practices, a
      quarter of fridges were freezing, thereby compromising the potency of many of the
      immunisation schedule vaccines.

PMID- 11824994
TI  - Payment policy for chemotherapy in public hospitals: a case for splitting DRG
      780/R63Z.
AB  - OBJECTIVE: To assess the appropriateness of the current way chemotherapy is
      classified in the Australian casemix classification system. METHOD: Secondary
      analysis of patient-level data for all cases of DRG 780 separated from Victorian
      hospitals with clinical costing systems in the years 1994/95, 1995/96 and 1996/97
      using the Chi-squared Automatic Interaction Detector (CHAID) option of Answer
      Tree Version 2.0. RESULTS: Different cancers have different costs. There is a
      significant difference (F=316.8, df=4, 11091, p=0.00) between the cost of colon
      cancer (mean=$289), breast cancer (mean=$481), lymphatic cancer (mean=$605),
      leukemia (mean=$1,118) and other cancers (mean=$512). The differences are
      sufficiently large that they meet the statistical criteria for splitting a DRG.
      CONCLUSION: Application of nationally agreed criteria for creation of Diagnosis
      Related Groups suggests that the existing DRG 780 should be split into five
      groups: colon, breast and lymphatic cancers, leukemia and a residual 'other
      cancers' category. The new groups increase the explanation of variation in costs
      (about a 10% reduction in variance). IMPLICATIONS: It is no longer valid for
      casemix development to be based on length of stay as a proxy for resource
      utilisation, especially for DRGs that are primarily same day.

PMID- 11824995
TI  - Outcomes from NHMRC public health research project grants awarded in 1993.
AB  - AIMS: In 1987, the Public Health Research and Development Committee (PHRDC) was
      established by the NHMRC as one mechanism to fund public health research in
      Australia. In 1993, it awarded 32 new and 31 continuing project grants. Given
      increasing interest in research accountability in Australia, we designed an audit
      to determine outcomes from this investment. We also explored grant recipients'
      views about sources of research funding and strategies to enhance research
      dissemination. METHOD: Self-administered survey, July 1999. MAIN RESULTS: We
      obtained a 69% response fraction. The majority of projects already had been
      completed with peer-reviewed articles the most common outputs. More than half
      (58%) of respondents 'strongly agreed' or 'agreed' that their research had
      influenced policy to improve public health and 69% that it had influenced
      practice. Study design was significantly associated with peer-reviewed output,
      whether self-reported (p=0.002) or corroborated by us (p=0.004). With respect to
      research funding, significantly more agreed that the NHMRC should enhance program
      grants for public health research than mechanisms through the Strategic Research
      Development Committee (p=0.013). The most highly rated strategy to enhance
      dissemination was greater demand for research results among policy makers.
      CONCLUSION: A pleasing proportion of projects funded by PHRDC in 1993 generated
      peer-reviewed publications and provided research training. Recipients perceive
      their research has influenced policy and practice. Recipients' views about
      strategies to increase funding for public health research are consistent with
      current reforms within the NHMRC. Policy makers emerge as a key target for
      training in research transfer.

PMID- 11824996
TI  - Developing national physical activity guidelines for Australians.
AB  - The process and outcome of developing National Physical Activity Guidelines for
      Australians is described. The guidelines provide a means of incorporating new
      data on physical activity into public health education.

PMID- 11824997
TI  - Drug information for consumers: should it be disease or medication specific?
      Results of a community survey.
AB  - OBJECTIVE: To investigate the information-seeking behaviour of medicine users.
      METHODS: A telephone survey and follow-up in-depth interviews of a random sample
      of the adult population in the Hunter Region, NSW, Australia. The survey sought
      information on medicine use, information seeking, and satisfaction and
      understanding of the information received. In-depth interviews examined the
      barriers and facilitators of information seeking. RESULTS: Seven hundred and
      eighty-six people completed the telephone survey and 58 completed the follow-up
      interviews. Over half (51%) of the medicine users sought information, primarily
      to 'manage' their medicines, such as how to use the medicine. Over 30% of the
      questions asked by users related to 'therapeutic choices', such as how well the
      medicine worked for a particular condition. Doctors and pharmacists were the most
      frequent sources of information. A small proportion (10%) reported a potential
      unmet need for medicines information by indicating they would have liked to ask a
      question, but did not, or were dissatisfied with the information they received.
      Barriers to information seeking included perceptions that health care
      professionals were 'too busy', and that they were unwilling to provide
      information. CONCLUSIONS: Physicians and pharmacists continue to play an
      important role in providing consumers with medicines information. Although the
      reported level of unmet need was low, a significant proportion identified needs
      relating to information on therapeutic choice, rather than 'classical' drug
      information. IMPLICATIONS: Medicines-related information for the public should
      include advice on comparative performance of drugs, and be provided within the
      wider framework of general health information.

PMID- 11824998
TI  - Burden of disease and gender in Victoria.

PMID- 11824999
TI  - Does cost affect access to non-prescription pharmaceuticals?

PMID- 11825000
TI  - Meanings and interpretations.

PMID- 11825001
TI  - Hepatitis C virus infection: an overview.
AB  - Hepatitis C virus is an RNA virus belonging to the Flaviviridae family. The
      diagnosis of hepatitis C virus infection was based on the detection of serum
      antibody to hepatitis C virus (anti-HCV) using immunoassay or recombinant
      immunoblot assay, or the direct detection of serum hepatitis C virus RNA using
      polymerase chain reaction. The anti-HCV positive rate in the general population
      or healthy blood donors is 0.5% to 4% worldwide. Parenteral transmission was the
      major route of hepatitis C virus infection. High-risk groups for hepatitis C
      virus infection included recipients of blood transfusion of which the blood
      donors were not screened for anti-HCV, intravenous drug abusers, hemophiliacs,
      and patients who have received hemodialysis. More than 80% of patients with
      hepatitis C virus infection progressed into chronicity, 20% to 30% of patients
      with chronic hepatitis C progressed to cirrhosis after 10 to 20 years of follow
      up, and some developed hepatocellular carcinoma. Hepatitis C virus was the most
      common cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma in
      Western countries and in Japan, where hepatitis B virus is not endemic.
      Interferon therapy at a dosage of 3 MU and subcutaneous injection 3 times per
      week for 6 months normalized serum transaminase in 50% of patients with chronic
      hepatitis C at the end of treatment. However, the relapse rate was high and only
      20% to 25% of patients sustained response 1 year after discontinuing therapy.
      Prolonged interferon therapy up to 12 to 18 months has been suggested to improve
      interferon efficacy by decreasing the relapse rate and thus increasing the
      sustained response rate. New interferon preparation such as consensus interferon
      and long-acting pegylated-interferon has recently shown better treatment response
      than the traditional interferon regimen. The combined regimen of interferon and
      ribavirin was shown to have better efficacy than interferon alone in treating
      patients with chronic hepatitis C.

PMID- 11825002
TI  - Oxytetracycline production by immobilized Streptomyces rimosus.
AB  - This study examined whether the production of oxytetracycline by Streptomyces
      rimosus TM-55 (CCRC 960061) would be improved with calcium alginate
      immobilization in submerged fermentation compared with free cells. Results showed
      that in 1-mL culture broth, free cells produced 121 to 124 microg of
      oxytetracycline, whereas immobilized cells produced 153 to 252 microg.
      Immobilization of the cells retarded the growth rate of S. rimosus but increased
      the length of the growth period and improved the oxytetracycline production. The
      specific oxytetracycline productivity was 33.3 to 34.2 mg in each gram of free
      dry cells and was 40.2 to 40.7 mg in immobilized dry cells. The optimum
      immobilization conditions were alginate 2% and bead diameter of 2.13 mm.
      Oxytetracycline production increased with increasing inoculum density but
      decreased with increasing bead diameter. Ethylenediaminetetraacetic acid or
      monovalent ions could react with calcium in the bead or replace it with sodium
      ion, thereby reducing the strength of the beads.

PMID- 11825003
TI  - Characteristics and potency of an acellular pertussis vaccine composed of
      pertussis toxin, filamentous hemagglutinin, and pertactin.
AB  - In an attempt to develop a safer pertussis vaccine, we successfully purified 3
      pertussis protective antigens-pertussis toxin, filamentous hemagglutinin, and a
      69-kDa outer membrane protein (also named pertactin), from Bordetella pertussis
      strain ATCC 9340. The toxicity of pertussis toxin could be effectively reduced by
      the treatment with formaldehyde 0.07% while preserving of a high degree of
      immunogenicity. By mixing purified pertussis antigens with diphtheria and tetanus
      toxoids (DT), we have formulated a DT acellular pertussis (DTaP) vaccine.
      Toxicity studies on body-weight gain in mouse, histamine sensitization,
      lymphocyte promoting, and Chinese hamster ovary cell clustering tests suggested
      that this DTaP vaccine is safer than a whole cell vaccine produced in France
      (DTP[F]). The formulated vaccine elicited high levels of anti-pertussis toxin
      antibodies in both mice and monkeys. In mice, a 2-fold neutralization of anti
      pertussis toxin antibodies was produced by DTaP compared with DTP(F) vaccine and
      an acellular vaccine manufactured in Japan (DTaP[J]). More importantly, in
      intracerebral challenge assay in mouse, this vaccine also provided a better
      protection than DTaP(J).

PMID- 11825004
TI  - Experimental studies on physiological and morphological aspects of Cysticercus
      cellulosae in pigs.
AB  - Three Small-Ear-Miniature, 3 Landrace-Small-Ear-Miniature, and one Douc-Yorkshire
      Landrace pigs were inoculated orally with 100 000 eggs of Zhengzhou strain or 10
      000 eggs of Harbin strain of Taenia solium. A total of 3739 cysticerci were
      recovered from 3 Small-Ear-Miniature and 3 Landrace-Small-Ear-Miniature pigs,
      giving an infection rate of 85.7% and a cysticercus recovery rate of 1.1%. The
      predilection sites of Cysticercus cellulosae in descending order were leg
      muscles, abdominal muscles, thoracic muscles, liver, head muscles, diaphragm,
      tongue, heart, trachea, and omentum/testes. Except 2 calcified cysticerci in the
      tongue, 2 in the heart, and 176 in the liver, the remaining cysticerci were all
      alive. The greatest number of cysticerci per 100 g of muscles or viscera was
      found in the head muscles, followed by the leg, diaphragm, heart, tongue,
      thoracic, abdominal, omentum, testes, and trachea. All cysticerci were evaginated
      in pig's bile after fluid was drawn out from cysticerci, whereas evagination
      occurred in only 83.2% of those without fluid drawing. In 364 evaginated
      cysticerci, the mean length and width of scolex, proglottid, and bladder, and
      diameter of rostellum and sucker were 826 x 747 microm, 5,370 x 1,734 microm,
      2,885 x 3,002 microm, 155 microm, and 253 microm, respectively. In the
      protoscolex, the mean number of segments was 33. Each cysticercus had 2 rows of
      rostellar hooks on the scolex, and the mean length and width of inner and outer
      hooks were 151 x 18 microm and 117 x 14 microm, respectively. The number of
      paired hooks ranged from 10 to 18.

PMID- 11825005
TI  - Risk factors of wheeze and allergy after lower respiratory tract infections
      during early childhood.
AB  - Lower respiratory tract infections (LRIs) during early childhood can lead to
      bronchial hyperreactivity or recurrent obstructive bronchitis. The role of LRIs
      in the pathogenesis of allergic diseases such as allergic rhinoconjunctivitis,
      atopic eczema, and bronchial asthma is less clear. The aim of this retrospective
      study was to determine the incidence of subsequent wheezing and atopy, and the
      known risk factors for allergic sensitization in 74 children hospitalized for
      acute LRIs of various etiologies from January 1994 through December 1994. Results
      showed that there are no differences in outcomes between patients with
      respiratory syncytial virus LRI, Chlamydia pneumoniae LRI, and LRIs caused by
      other agents. Although lower respiratory tract illnesses, especially those caused
      by respiratory syncytial virus during infancy, were associated with an increased
      risk of subsequent wheezing during early childhood, wheezing tended to disappear
      with increasing age in many children. This study also found recurrent episodes of
      wheezing during the first 5 years of life, and symptoms suggestive of allergic
      rhinoconjunctivitis were the only factors predictive of subsequent diagnosis of
      asthma for children who had LRIs during early childhood. In conclusion, this
      study suggests that prevention of recurrent wheezing LRIs and good control of
      allergic rhinoconjunctivitis is critical for preventing subsequent development of
      bronchial asthma.

PMID- 11825006
TI  - Clinical characteristics of neonatal lupus erythematosus.
AB  - Neonatal lupus erythematosus is a rare disorder caused by transplacental
      autoantibodies from the mother to the fetus. This syndrome is characterized by
      congenital heart block and/or cutaneous lesion. A total of 10 cases of neonatal
      lupus erythematosus were diagnosed at the National Taiwan University Hospital
      from 1988 through 1998. The incidence of cardiac anomaly and other clinical
      features in patients with neonatal lupus erythemayosus in this study was compared
      with those in previous studies. Results showed that 50% of patients had
      congenital heart block and/or cutaneous lesion, which is compatible to previous
      statistics. However, the findings showed that 80% of the patients were female and
      90% of the mothers had acquired an autoimmune disorder, which were much higher
      compared with that of other studies. To date, no definite treatment is suggested
      prenatally to prevent the occurrence of congenital heart block, but careful
      maternal screening and serial fetal echocardiogram are warranted.

PMID- 11825007
TI  - Antimicrobial resistance and serotype distribution of Streptococcus pneumoniae
      infections in Kaohsiung from 1996 through 1999.
AB  - A total of 89 isolates of Streptococcus pneumoniae were obtained from 86 patients
      during the period from November 1996 through September 1999 at the Kaohsiung
      Medical University Hospital. The purpose of this study was to determine the
      antimicrobial susceptibilities and the distribution of serotypes of these
      isolates, and to correlate these findings with the clinical characteristics of
      patients. Twenty-one (23.6%) isolates were obtained from patients aged below 5
      years, and 38 (42.7%) from patients aged over 65 years. These 86 patients
      included 53 pneumonia, 13 bacteremia (including 6 with septic shock), 8 urinary
      tract infection, 8 soft tissue infections, 7 acute exacerbation of chronic
      bronchitis, 2 ophthalmic infection, and 2 cholecystitis cases. The most frequent
      serotypes were types 20 (10.1%), 6 (9%), 10 (9%), 11 (9%), and 23 (9%). All
      isolates were included in the serotypes represented in the 23-valent pneumococcal
      vaccine. Thirty-four (38.2%) isolates showed reduced penicillin susceptibility by
      the E-test. The predominant serotypes of penicillin-resistant S. pneumoniae were
      types 11 (17.6%), 7 (14.7%), 6 (8.8%), 8 (8.8%), and 23 (8.8%). All isolates were
      susceptible to vancomycin. Resistance rate to erythromycin was 49.4%,
      chloramphenicol, 20.2%; and trimethoprim/sulfamethoxazole, 61.8%. Multiple
      resistance (> or = 3 classes of antibiotics) was found in 28 (31.5%) isolates, of
      which the majority were serotypes 11 (14.3%), 7 (14.3%), 6 (10.7%), 8 (10.7%),
      and 23 (10.7%).

PMID- 11825009
TI  - Invasive infections due to vancomycin-resistant enterococci in adult patients.
AB  - Since 1990, vancomycin-resistant enterococci have emerged as important nosocomial
      pathogens. Invasive infections caused by these organisms have challenged most
      physicians because they are resistant to multiple antibiotics. We analyzed the
      clinical characteristics of adult patients with invasive vancomycin-resistant
      enterococci infections in the National Taiwan University Hospital from January
      1993 through December 2000. A total of 11 adult patients were identified, 9 of
      whom had bacteremia (7 caused by vancomycin-resistant Enterococcus faecalis and 2
      by vancomycin-resistant Enterococcus faecium) and one each had thoracic empyema
      (vancomycin-resistant E. faecium) and peritonitis (vancomycin-resistant E.
      faecium). Five patients had rectal swab cultures positive for vancomycin
      resistant enterococci; 4 of them had underlying malignancies. The majority (91%)
      of these patients had prolonged hospitalization and prior long-term use of broad
      spectrum cephalosporins (ceftriaxone, ceftazidime, or cefepime) or anti-anaerobic
      agents (clindamycin or metronidazole). The crude mortality rate was 64%. In
      conclusion, invasive infection caused by vancomycin-resistant enterococci is an
      emerging problem among hospitalized patients in Taiwan, particularly those with
      severe underlying diseases and exposure to multiple antibiotics.

PMID- 11825010
TI  - Deep neck infections in children.
AB  - From December 1989 through 1998, a total of 68 children with deep neck infection
      were enrolled into this study. The mean age was 5.9 years (range, 1 month-15.8
      years). Infections in the retropharyngeal space (36.7%) were most common,
      followed by parapharyngeal space (30.8%), peritonsillar space (20.6%), and
      submandibular space (11.9%). Fever, neck pain, and swelling were the most
      frequent symptoms. The most common pathogens were viridans streptococci (41%,
      16/39) and Staphylococcus aureus (26%, 10/39). Other isolates included Prevotella
      spp., Veillonella spp., Klebsiella pneumoniae, Escherichia coli, Morganella spp.,
      and Enterobacter spp. Mixed infection was found in 46% (18/39) of patients. The
      mean duration of hospitalization was 12.4 days (range, 2-45 days). Complete
      resolution was achieved in 61 (89.7%) children. Complications occurred in 7
      patients, including recurrence, mediastinal spread, bacteremia, and suppurative
      thyroiditis; the patient with mediastinal spread plus bacteremia died. Five
      patients had congenital cyst and 4 of them had complications or
      recurrence/relapse. In conclusion, infections in the retropharyngeal space and
      polymicrobial infections were most common in deep neck infection of Taiwan
      children.

PMID- 11825008
TI  - Empirical monotherapy with meropenem in serious bacterial infections in children.
AB  - The efficacy and safety profile of meropenem were analyzed according to data
      collected from hospitalized pediatric patients aged 4 days to 20 years who had
      serious bacterial infections and were treated in a major teaching hospital in
      Taipei. Of the 53 patients enrolled, 47 were analyzed for clinical efficacy and
      53 for safety. The satisfactory clinical response rate was 57% in lower
      respiratory tract infection, 58% in septicemia, 100% in complicated urinary tract
      infection, osteomyelitis, and central nervous system infection, 83% in skin and
      soft tissue infection, and 93% in intra-abdominal infection. Eleven (21%)
      patients experienced adverse events related to meropenem. The most commonly
      observed adverse reactions were elevated hepatic enzymes (7.5%), increased
      alkaline phosphatase (3.8%), and thrombocytosis (3.8%). There was no meropenem
      related seizure, withdrawal, or death. The results of this study suggested that
      meropenem is well tolerated even in young infants, and is effective in treating
      serious childhood bacterial infection. However, this study also identified a
      proportion of hospitalized pediatric patients with isolates that were resistant
      to meropenem. The trends in meropenem resistance among nosocomially acquired
      bacteria should be monitored closely.

PMID- 11825011
TI  - Pasteurella multocida bacteremia due to non-bite animal exposure in cirrhotic
      patients: report of two cases.
AB  - Pasteurella species are very small gram-negative coccobacilli. They are normal
      flora found in the oral cavity and gastrointestinal tract of many animals, and
      can cause various infections including septicemia and pneumonia. Human infection
      with Pasteurella multocida occurs commonly as a localized cellulitis caused by
      animal bites. This report described 2 rare cases of P. multocida bacteremia in
      patients with liver cirrhosis and esophageal varices. Both patients had a history
      of contact with sick-appearing stray dogs, but neither had been bitten. P.
      multocida bacteremia should be included in the differential diagnosis of febrile
      cirrhotic patients with esophageal varices who have a history of non-bite animal
      exposure. Avoidance of animal contact by immunocompromised patients is the most
      important factor in preventing pasteurellosis.

PMID- 11825012
TI  - Perinatal cytomegalovirus infection complicated with pneumonitis and adrenalitis
      in a premature infant.
AB  - Cytomegalovirus causes pneumonia, hepatitis, thrombocytopenia, and hemolytic
      anemia. Cytomegalovirus adrenalitis in premature infants, however, is rare. This
      report described a premature newborn who had progressively worsening
      hyperbilirubinemia, pancytopenia, and hepatosplenomegaly at the age of 4 days.
      The baby's mother had prolonged rupture of amniotic membrane for about 8 weeks.
      The infant received exchange blood transfusion, empiric antibiotics treatment,
      and mechanical ventilation. Pneumonia and sepsis developed at the age of 18 days.
      Serum anticytomegalovirus immunoglobulin M and urine virus culture were positive
      for cytomegalovirus. The baby died at the age of 22 days. Autopsy showed
      cytomegalovirus infection complicated with interstitial pneumonitis and pulmonary
      edema, subacute bronchopulmonary dysplasia with interstitial fibrosis, and
      adrenalitis. We concluded that the functional status of the adrenal glands in
      cytomegalovirus-infected premature newborns who have unexplained electrolytes
      imbalance, fever, diarrhea, weight loss, or hypotension should be closely
      followed because of the possible involvement of adrenal glands.

PMID- 11825013
TI  - Fish allergy in atopic children.
AB  - The prevalence of fish allergy among 11 atopic children with elevated levels of
      specific immunoglobulin (Ig) E for cod was determined. None of the children had a
      history of fish allergy. All of the children had asthma and allergic rhinitis and
      5 of them had also atopic dermatitis. The children underwent allergy skin tests
      (codfish, tuna, catfish, salmon, flounder, and bass), specific IgE tests (salmon,
      trout, tuna, eel, and mackerel), and food challenge tests. Skin tests in cod
      specific IgE-positive children were positive for codfish in 4 children, tuna in
      2, catfish in 2, salmon in 6, flounder in one, and bass in 2. Three children had
      elevated specific IgE for salmon, 5 for trout, 8 for tuna, 4 for eel, and 4 for
      mackerel. Oral fish challenge with 10 g of fish did not result in positive
      reaction in any of the children. In conclusion, a positive food challenge test
      provided the only definitive confirmation of fish allergy, whereas positive
      allergy skin tests or positive specific IgE tests were less reliable. Skin tests
      and in vitro specific IgE assays were not correlated with clinical symptoms of
      fish allergy, and the results of these 2 tests did not correlate with each other
      in this study.

PMID- 11825014
TI  - The cornea through the eyes of knockout mice.

PMID- 11825015
TI  - Identification of a novel fluorophore, xanthurenic acid 8- O -beta-D-glucoside in
      human brunescent cataract.
AB  - We have identified the chemical structure of a novel protein-unbound fluorescent
      glucoside (Fl-Glc), found to be far more abundant in the human brunescent
      cataractous lens nuclei than in non-brunescent ones. Our earlier experiments
      showed that long-term incubation of the protein-free filtrate of non-brunescent
      cataractous nuclei generated increasing amounts of a particular yet to be
      characterized fluorophore (Fl-X). High performance liquid chromatography (HPLC)
      analyses revealed Fl-X and Fl-Glc to be identical. HPLC-electrospray ionization
      mass spectrometry (HPLC-ESI-MS) disclosed the molecular weights (MW) of Fl-X and
      its beta-glucosidase-digest (Fl-X-aglycon) to be 367 and 205, respectively. Fl-X
      aglycon and authentic xanthurenic acid (MW = 205) not only eluted at exactly the
      same retention time on HPLC but also revealed their protonated ions at the same
      m/z of 206.1 by positive ion analysis on HPLC-ESI-MS. These results suggest that
      Fl-X ( = Fl-Glc) is a beta-glucoside of xanthurenic acid. Fl-Glc was finally
      identified as xanthurenic acid 8- O -beta- D -glucoside because the retention
      times of both completely agreed with three kinds of HPLC conditions.

PMID- 11825016
TI  - Expression of myocilin/TIGR in normal and glaucomatous primate optic nerves.
AB  - Myocilin/TIGR was the first molecule discovered to be linked with primary open
      angle glaucoma (POAG), a blinding disease characterized by progressive loss of
      retinal ganglion cells. Mutations in myocilin/TIGR have been associated with age
      of disease onset and severity. The function of myocilin/TIGR and its role in
      glaucoma is unknown. Myocilin/TIGR has been studied in the trabecular meshwork to
      determine a role in regulation of intraocular pressure. The site of damage to the
      axons of the retinal ganglion cells is the optic nerve head (ONH). The
      myocilin/TIGR expression was examined in fetal through adult human optic nerve as
      well as in POAG. Myocilin/TIGR was expressed in the myelinated optic nerve of
      children and normal adults but not in the fetal optic nerve before myelination.
      Also examined was the expression in monkeys with experimental glaucoma. The
      results demonstrate that optic nerve head astrocytes constitutively express
      myocilin/TIGR in vivo in primates. Nevertheless, myocilin/TIGR is apparently
      reduced in glaucomatous ONH. The colocalization of myocilin/TIGR to the myelin
      suggests a role of myocilin/TIGR in the myelinated optic nerve.

PMID- 11825017
TI  - Regulation of MMP-9 production by human corneal epithelial cells.
AB  - The matrix metalloproteinases, MMP-2 and MMP-9, are known to be critical
      extracellular-remodeling enzymes in wound healing and other diseases of the
      ocular surface. This study investigated the regulation of MMP-2 and MMP-9 in
      human corneal epithelial cells by growth factors and pro-inflammatory cytokines
      (IL-1beta and TNF-alpha) they are exposed to, and by doxycycline, a medication
      used to treat ocular surface disease. Primary human corneal epithelial cell
      cultures were treated with one of the following cytokines (IL-1alpha, IL-1beta,
      IL-6, IL-8, TNF-alpha) or growth factors (EGF, HGF, KGF, PDGF-BB, TGF-alpha, TGF
      beta), with or without their corresponding inhibitors. The conditioned media were
      collected after 24 hr for gelatin zymography and MMP-9 activity assay. Total RNA
      was extracted from the cells treated for 6 hr and was subjected to RT-PCR and
      Northern hybridization. Between the two gelatinases, MMP-2 and MMP-9, detected by
      zymography, the 92 kDa MMP-9 in the conditioned medium was markedly up-regulated
      by the pro-inflammatory cytokines, IL-1beta and TNF-alpha. The MMP-9 protein and
      activity were dose-dependently stimulated by IL-1beta or TNF-alpha at 0.1, 1.0
      and 10 ng ml(-1). This up-regulation was nearly abolished by neutralizing
      antibodies (IL-1beta and TNF-alpha) and by IL-1 receptor antagonist. Semi
      quantitative RT-PCR and Northern hybridization disclosed that the MMP-9
      transcript was also markedly up-regulated in a dose-dependent manner by IL-1beta
      and TNF-alpha. Doxycycline (10 microg ml(-1)) suppressed MMP-9 protein level and
      activity, but not its mRNA, that was stimulated by IL-1beta and TNF-alpha (1 ng
      ml(-1)). In contrast, the 72 kDa MMP-2 was not significantly modulated by any of
      these cytokines. In conclusion, production of MMP-9 is stimulated by the pro
      inflammatory cytokines, IL-1beta and TNF-alpha. These factors may play a role in
      the pathogenesis of MMP-9 mediated corneal matrix degradation. The efficacy of
      doxycycline in treating ocular surface diseases may be related to its ability to
      suppress MMP-9 production in the corneal epithelium.

PMID- 11825018
TI  - Expression of transcription factor AP-1 in rat lens epithelial cells during wound
      repair.
AB  - We examined the spatial and temporal expression patterns of proteins and mRNAs of
      the components of transcription factor activator protein 1 (AP-1) to examine the
      activation pattern of lens epithelial cells during lens wound repair following an
      anterior capsular injury. One eye of adult Wistar rats (n = 106) were used. After
      making a lens anterior capsule incision with a hypodermic needle, the affected
      eye was enucleated 0 and 30 min, 1, 3, 5, 8, 10, 15, 20, 24 hr after injury.
      Forty six globes were processed for in situ hybridization with oligonucleotide
      probes for c-fos, fosB, c-jun, junB and junD mRNAs, and 60 globes were
      immunohistochemically analysed using anti-c-Fos and anti-c-Jun antibodies. Normal
      lens epithelial cells expressed mRNA signals for junD, but not for c-fos, fosB, c
      jun, and junB. mRNAs for c-fos, fosB, c-jun, and junB were detected in the whole
      lens epithelium from the vicinity to the wound to the equator from 30 min to 8 hr
      post-injury with their peaks after 30 min to 1 hr, but were no longer detected at
      10 hr or later. Expression of c-fos mRNA in the equatorial lens cells was more
      marked than that of c-jun mRNA. Immunohistochemistry showed that c-Fos protein
      was expressed in the lens epithelial cells in both the anterior and equatorial
      regions of the injured lens from 1 to 10 hr after injury, and was no longer
      detected at 12 hr. C-Jun protein was detected only in the equatorial lens cells
      from 1 to 5 hr after injury, and was no longer detected at 8 hr. Lens epithelial
      cells except those in the equatorial region did not express c-Jun protein. These
      findings indicate that transcriptional activation of lens epithelial cells is
      initiated in the very early phase after the lens injury, i.e. 30 min post-injury,
      suggesting that AP-1 may play important roles in regulating lens cell behavior
      during lens wound repair in rats.

PMID- 11825019
TI  - Chondroitin sulphate proteoglycan is involved in lens vesicle morphogenesis in
      chick embryos.
AB  - Proteoglycans have been implicated in the invagination and formation of various
      embryonal cavitied primordia. In this paper the expression of chondroitin
      sulphate proteoglycan (CSPG) is analysed in the lens primordium during lens
      vesicle formation, and demonstrate that this proteoglycan has a specific
      distribution pattern with regard to invagination and fusion processes in the
      transformation of placode into lens vesicle. More specifically, CSPG was detected
      in: (1) the apical surface of lens epithelial cells, where early CSPG expression
      was observed in the whole of the lens placode whilst in the vesicle phase it was
      restricted to the posterior epithelium; (2) intense CSPG expression in the basal
      lamina, which remained constant for the entire period under study; (3) CSPG
      expression in the intercellular spaces of the lens primordium epithelium, which
      increased during the invagination of the primordium and which at the vesicle
      stage was more evident in the posterior epithelium; and (4) CSPG expression on
      the edges of the lens placode both prior to and during fusion. Treatment with
      beta- D -xyloside causes significant CSPG depletion in the lens primordium
      together with severe alterations in the invagination and fusion of the lens
      vesicle; this leads to the formation of lens primordia which in some cases remain
      practically flat or show partial invagination defects or fusion disruption.
      Similar results were obtained by enzyme digestion with chondroitinase AC but not
      with type II heparinase, which indicates that alterations induced by beta- D 
      xyloside were due to interference in CSPG synthesis. The findings demonstrate
      that CSPG is a common component of the lens primordium at the earliest
      developmental stages during which it undergoes specific modifications. It also
      includes experimental evidence to show that 'in vivo' CSPG plays an important
      role in the invagination and fusion processes of the lens primordium.

PMID- 11825020
TI  - Proteome survey of proliferating and differentiating rat RPE-J cells.
AB  - The suitability of the rat derived SV-40T immortalized RPE-J cell line for
      identifying proteome changes associated with RPE differentiation was evaluated by
      surveying changes in protein expression levels. Rat RPE-J cells were induced to
      undergo differentiation in culture by growth at the nonpermissive temperature of
      40 degrees C in the presence of retinoic acid. Total proteins were extracted from
      cells grown under proliferating or differentiating conditions and separated by 1D
      and 2D gel electrophoresis. Gel spots were excised, digested in situ with
      trypsin, and analysed by mass spectrometry to identify proteins. Computer
      assisted image analysis was used to align gel patterns and quantify spot
      intensities. Neither proliferating nor differentiating RPE-J cell cultures
      exhibited detectable levels of cellular retinaldehyde-binding protein, RPE65, 11-
      cis -retinol dehydrogenase or lecithin retinol acyl transferase, suggesting that
      RPE-J cells are not appropriate for visual cycle studies. About 18% of the 61
      identified proteins appear to change expression levels with the cell growth
      conditions. Seven proteins appeared to be up-regulated and four proteins down
      regulated when the cells were changed from proliferating to differentiating
      culture conditions. The majority of the apparent changes in protein expression
      levels were associated with stress response genes. Significant changes in the
      apparent mass and charge properties of proteins were also observed and for select
      proteins, the modifications appeared to be correlated with cell growth
      conditions. The results demonstrate that proteome differences in RPE-J cells
      associated with growth conditions can be identified and support the suitability
      of RPE-J cells for more targeted and/or more global proteome analysis of RPE
      differentiation.

PMID- 11825021
TI  - Concentric retinitis pigmentosa: clinicopathologic correlations.
AB  - Progressive concentric (centripetal) loss of vision is one pattern of visual
      field loss in retinitis pigmentosa. This study provides the first
      clinicopathologic correlations for this form of retinitis pigmentosa. A family
      with autosomal dominant concentric retinitis pigmentosa was examined clinically
      and with visual function tests. A post-mortem eye of an affected 94 year old
      family member was processed for histopathology and immunocytochemistry with
      retinal cell specific antibodies. Unrelated simplex/multiplex patients with
      concentric retinitis pigmentosa were also examined. Affected family members of
      the eye donor and patients from the other families had prominent peripheral
      pigmentary retinopathy with more normal appearing central retina, good visual
      acuity, concentric field loss, normal or near normal rod and cone sensitivity
      within the preserved visual field, and reduced rod and cone electroretinograms.
      The eye donor, at age 90, had good acuity and function in a central island.
      Grossly, the central region of the donor retina appeared thinned but otherwise
      normal, while the far periphery contained heavy bone spicule pigment.
      Microscopically the central retina showed photoreceptor outer segment shortening
      and some photoreceptor cell loss. The mid periphery had a sharp line of
      demarcation where more central photoreceptors were near normal except for very
      short outer segments and peripheral photoreceptors were absent. Rods and cones
      showed abrupt loss of outer segments and cell death at this interface. It is
      concluded that concentric retinitis pigmentosa is a rare but recognizable
      phenotype with slowly progressive photoreceptor death from the far periphery
      toward the central retina. The disease is retina-wide but shows regional
      variation in severity of degeneration; photoreceptor death is severe in the
      peripheral retina with an abrupt edge between viable and degenerate
      photoreceptors. Peripheral to central gradients of unknown retinal molecule(s)
      may be defective or modify photoreceptor degeneration in concentric retinitis
      pigmentosa.

PMID- 11825023
TI  - Anaylsis of birefringence during wound healing and remodeling following alkali
      burns in rabbit cornea.
AB  - The use of synthetic inhibitors of metalloproteinases (SIMP) or
      medroxyprogesterone (MP) can prevent or significantly delay the ulceration of
      alkali-injured corneas by influencing collagen degradation. We have examined the
      remodeling of rabbit corneal stroma following alkali injury and have assessed the
      effect of SIMP and MP treatment. Following a defined alkali injury to the rabbit
      cornea, animals were divided into three subgroups, one group treated with topical
      beta-mercaptomethyl tripeptide (SIMP), one treated by subconjunctival injection
      of MP and one treated with a control solution. The corneal tissue was taken at 3
      days, 1, 2, 3, 4, 9 and 26 weeks after alkali injury and prepared for light
      microscopy and transmission electron microscopy (TEM). A quantitative measurement
      of birefringence, in terms of the optical path difference (OPD), was made using a
      modified polarized microscopy technique based on the analysis of interference
      colours. The results showed that SIMP effectively prevented deep corneal
      ulceration. MP could delay the ulceration and the corneas treated with MP
      appeared to have better transparency than the other groups. There was a
      significant difference of the OPD between the anterior (5.8 +/-0.3 nm) and
      posterior (7.8 +/-0.4 nm) stroma of the normal cornea (P<0.001). The OPD values
      from the central corneas from alkali-injured eyes were generally lower than
      normal during the first 4 weeks and then gradually recovered to the normal level
      or above, except for the posterior stroma of the MP-treated eyes. We found that
      the OPD changes were very dependent on the presence of corneal lesions. The
      stroma near corneal ulceration, scar tissue, calcified stroma and the retro
      corneal collagen layer showed a significant reduction of birefringence (lower OPD
      values). These OPD values remained much lower than normal up to the end of the
      experiment. TEM showed disrupted corneal stroma in all three groups, with thinner
      scar tissue in the MP group. The fibril diameters did not change significantly 3
      days and 1 week after the alkali burns (27.1+/-2.3 nm in the control group,
      27.3+/-2.2 nm in the SIMP group and 27.7+/-2.1 nm in the MP group) and there were
      no differences compared with 29.7+/-1.7 nm of the normal cornea (P>0.05). After 2
      weeks of tissue remodeling, the fibril diameters in alkali-injured corneas showed
      a large variation (the range was between 11.5 and 80 nm) with a bimodal
      distribution, especially in the control group. The technique presented here for
      birefringence evaluation can provide an alternative way to monitor wound healing
      and tissue remodeling, both visually and quantitatively.

PMID- 11825022
TI  - Outer segment phagocytosis by cultured retinal pigment epithelial cells requires
      Gas6.
AB  - The function and viability of vertebrate photoreceptors requires the daily
      phagocytosis of photoreceptor outer segments (OS) by the adjacent retinal pigment
      epithelium (RPE). We demonstrate here a critical role in this process for Gas6
      and by implication one of its receptor protein tyrosine kinases (RTKs), Mertk
      (Mer). Gas6 specifically and selectively stimulates the phagocytosis of OS by
      normal cultured rat RPE cells. The magnitude of the response is dose-dependent
      and shows an absolute requirement for calcium. By contrast the Royal College of
      Surgeons (RCS) rat RPE cells, in which a mutation in the gene Mertk results in
      the expression of a truncated, non-functional receptor, does not respond to Gas6.
      These data strongly suggest that activation of Mertk by its ligand, Gas6, is the
      specific signaling pathway responsible for initiating the ingestion of shed OS.
      Moreover, photoreceptor degeneration in the RCS rat retina, which lacks Mertk,
      and in humans with a mutation in Mertk, strongly suggests that the Gas6/Mertk
      signaling pathway is essential for photoreceptor viability. We believe that this
      is the first demonstration of a specific function for Gas6 in the eye.

PMID- 11825024
TI  - Visual deprivation stimulates the exchange of the fibrous sclera into the
      cartilaginous sclera in chicks.
AB  - Form deprivation myopia in chicks is a widely accepted model to study visually
      regulated postnatal ocular growth. The chick sclera has a cartilaginous layer as
      well as the fibrous layer found in mammals. It appears that a dynamic
      relationship exists between these two layers during visual deprivation-induced
      growth. The changes in the fibrous sclera of myopic eyes, however, have not been
      previously described. This investigation is focused on the comparative
      morphological analyses of the cartilaginous and fibrous scleral changes in myopic
      chick eyes. The fibrous scleral changes in the posterior segment of myopic eyes
      were examined in detail using light and electron microscopy, and the expression
      of growth factors was analysed by immunohistochemistry. In the posterior segment
      of myopic eyes the border between the cartilaginous and fibrous layers was
      indistinct because of collagen bundles of the fibrous sclera that spread into the
      cartilaginous sclera, whereas in control eyes the distinction was clear. Various
      types of transitional cells, from fibroblast-like mesenchymal cells to
      chondrocytes, were found in the border between the cartilaginous and fibrous
      layers. Collagen fibrillar diameters of the fibrous sclera in the posterior
      segment of myopic eyes were smaller than in control, whereas those in the
      equatorial segment were almost the same in myopic and control eyes although the
      distribution of sizes was obviously different. Thus, changes in the fibrous
      sclera in myopic eyes of chicks seem to be similar to scleral changes in myopic
      eyes of mammals. The cells in the posterior sclera of myopic eyes were more
      intensely immunostained for TGF-beta and IGF-II than control, whereas no
      immunoreaction of TGF-alpha could be detected in either control or myopic eyes.
      These results suggest that the structural characteristics of the posterior sclera
      are different from those of the anterior and equatorial segments.
      Undifferentiated mesenchymal cells might be concentrically distributed
      exclusively in the innermost layer of posterior fibrous sclera. TGF-beta and IGF
      II might influence cell growth, differentiation, and migration in the exaggerated
      scleral growth accompanying myopia.

PMID- 11825025
TI  - Purification and characterization of a novel 88 kDa protein from serum and
      vitreous of patients with Eales' disease.
AB  - Eales' disease is a perivasculitis that affects the peripheral retina of young
      adults and results in recurrent vitreous hemorrhage. Although increased oxidative
      stress and decreased antioxidant defense have been reported to be associated with
      Eales' disease, the exact cause for the disease and its pathogenesis are not
      known. Here is reported the identification, purification and characterization of
      a new protein from the serum and vitreous of patients with Eales' disease. This
      protein was purified using preparative electrophoresis and HPLC. The purified
      protein had a retention time of 9.2 min in RP HPLC. Its molecular weight as
      determined by gel permeation chromatography was 88 kDa hence, it was termed as 88
      kDa protein. Alcian blue and Schiffs staining revealed 88 kDa protein to be a
      glycoprotein. Proteins purified from both serum and vitreous exhibited anti lipid
      peroxidation effect on erythrocyte when added during in vitro assay of
      thiobarbuteric acid reactive substances (TBARS). In addition to this property the
      protein also has Fe(2+)sequestering effect. The anti TBARS activity of 88 kDa
      protein was completely inhibited by 0.1 m M concentration of parachlromercuric
      benzoate (PCMB) and 5,5' dithiobis(2-nitrobenzoic acid) DTNB. The total thiol
      content (cysteine) of the purified 88 kDa protein was found to be 8% by mass.
      Eighty eight kDa protein from both the sources namely vitreous and serum are
      immunologically identical when studied using polyclonal antibodies raised in goat
      against purified serum protein. The N terminal sequence of 88 kDa protein by
      automated Edman's degradation chemistry is A D D P N S L S P S A F A E A L A L L
      R D S X L A R F V. The protein and DNA data base search revealed no match to 88
      kDa protein and hence this was considered as unique protein. Further knowledge on
      the in vivo function of 88 kDa protein is very important to understand its role
      in the pathogenesis of Eales' disease.

PMID- 11825027
TI  - Protection of photoreceptor cells in adult rats from light-induced degeneration
      by adaptation to bright cyclic light.
AB  - Light history has been shown to affect the susceptibility of the albino rat
      retina to the damaging effects of constant light exposure. Retinas of animals
      raised in relatively bright cyclic light are protected against light-induced
      degeneration compared with dim-reared animals. These effects were observed in
      animals raised from birth in bright cyclic light and are part of an adaptive
      response that protects photoreceptors from stress-induced degeneration. To
      determine if retinas of adult animals are capable of such adaptive changes or
      flexibility by switching between different light environments which do not
      pathologically damage photoreceptor cells, albino rats were maintained in less
      than 250 lux cyclic light for more than 3 weeks. At 12-13 weeks of age, they were
      placed into 800 lux cyclic light for 1 week, after which they were exposed to
      constant illumination of 1500-lux for 1, 3 or 7 days. Retinal function was
      evaluated by electroretinography and photoreceptor cell death was quantified by
      measuring outer nuclear layer thickness. After 1 week in bright cyclic light, the
      retinas were completely protected against 1 day constant light exposure that
      significantly damaged retinas of animals without 800 lux cyclic light adaptation.
      Significant protection was also observed in 3 day constant light exposed animals;
      limited protection occurred after 7 days exposure. These results indicate that
      the retinas of adult rats adapted to bright cyclic light within certain ranges
      that did not significantly damage photoreceptor cells are protected from constant
      light challenge. This phenomenon is a post-developmental response that
      demonstrates a remarkable plasticity of the retina. The mechanism(s) underlying
      the ability of this adaptation/flexibility in protecting photoreceptors could
      involve endogenous molecules that encompass many aspects of retinal cell and
      molecular biology and physiology. Identification of these molecules may provide
      insight into the development of therapeutic approaches to treat retinal
      degeneration.

PMID- 11825026
TI  - Photoreceptor rescue after low-dose intravitreal IL-1beta injection in the RCS
      rat.
AB  - Photoreceptor survival in the dystrophic rat was evaluated following
      administration of IL-1beta at dosages much lower than those used previously for
      this purpose. Royal College of Surgeons rats (pink-eyed, pigmented, or non
      dystrophic) received 1 microl intravitreal injections of murine recombinant IL
      1beta (0.5, 2, or 5 microg ml(-1); at 3 or 4 weeks of age). Eyes were harvested 4
      weeks later and outer nuclear layer profiles counted. Additional animals received
      intravitreal basic fibroblast growth factor (1000 microg ml(-1)), or vehicle
      alone. Others were treated with IL-1beta to evaluate the inflammatory response
      (CD45+ profiles) or visual function via opto-kinetic response. IL-1beta was
      associated with photoreceptor rescue that was both dose-dependent and comparable
      to that seen following high-dose basic fibroblast growth factor. Significant
      anatomical rescue relative to controls was seen in both pink-eyed and pigmented
      strains, although the degree and distribution varied between strains. Functional
      rescue was confirmed by opto-kinetic response using the pigmented strain. At 5
      microg ml(-1), IL-1beta resulted in numerous CD45+ profiles within the retina and
      vitreous. Infiltration peaked at 48 hr and was minimal at 4 weeks, without
      dysplastic sequelae. IL-1beta therefore induces visually significant
      photoreceptor rescue in a potent, dose-dependent manner that need not entail
      cytoarchitectural disruption. This is consistent with the known association
      between injury and rescue in the rat retina. Neuroprotection may be a general, if
      under-appreciated, consequence of inflammatory cascade activation.

PMID- 11825028
TI  - Lunar synchronization of in vitro steroidogenesis in ovaries of the golden
      rabbitfish, Siganus guttatus (Bloch).
AB  - To assess the relationship between lunar cycle and steroidogenesis in the ovaries
      of the golden rabbitfish, Siganus guttatus, the intact follicles of oocytes were
      incubated in vitro with human chorionic gonadotropin (hCG) and seven steroid
      hormones, 17alpha,20beta-dihydroxy-4-pregnen-3-one (DHP), 17alpha,20beta,21
      trihydroxy-4-pregnen-3-one (20beta-S), 17alpha-hydroxyprogesterone (17alpha-OHP),
      progesterone (P), cortisol, estradiol-17beta (E2) and testosterone, during the
      two lunar phases, the new moon (1 week before spawning) and the first lunar
      quarter (just before spawning). Around the new moon, germinal vesicle breakdown
      (GVBD) could not be induced by addition of hCG or any steroid hormones. Around
      the first lunar quarter, GVBD was induced by addition of hCG, DHP, 20beta-S,
      17alpha-OHP, P, and cortisol. DHP was the most potent steroid hormone. When the
      intact follicles of oocytes were incubated with hCG in both lunar phases, the
      production of E2 and DHP measured by enzyme immunoassay decreased and increased
      significantly from the new moon to the first lunar quarter, respectively. These
      results suggest that the ovarian follicles produce E2 around the new moon and DHP
      around the first lunar quarter and that the production/conversion of the steroid
      hormones is under the influence of gonadotropin(s). The synchronous increase in
      ovarian activity supports the hypothesis that lunar periodicity is a major factor
      for the ovarian development of S. guttatus.

PMID- 11825029
TI  - Changes in hepatic vitellogenin mRNA levels during oocyte development in the
      Japanese eel, Anguilla japonica.
AB  - The induction of vitellogenesis is a complex process requiring coordinated
      control and expression of many hepatic gene products, such as vitellogenin (VTG).
      To investigate the regulation of VTG synthesis, knowledge of the molecular
      genetics of VTG is required. Here, the authors have isolated a partial cDNA
      encoding Japanese eel VTG using an immunoscreening technique. This cDNA contained
      an open reading frame of 1629 bp, predicted to encode 543 amino acid residues,
      the sequence of which showed high homology with the VTG of other fishes. Northern
      blot analysis yielded a VTG transcript of approximately 5.8 kb from eel hepatic
      tissue. Experimentally, VTG synthesis could be induced by treatment with salmon
      pituitary homogenate. The levels of VTG mRNA in the liver during the artificial
      maturation of female Japanese eels correspond well to levels of E2 and VTG in the
      serum.

PMID- 11825030
TI  - Relationships between CB1 cannabinoid receptors and pituitary endocrine cells in
      Xenopus laevis: an immunohistochemical study.
AB  - The distribution of the cannabinoid CB1 receptor and its relationships with
      individual endocrine cell types were investigated by immunohistochemistry in the
      anterior lobe of the Xenopus adenohypophysis. By use of a specific primary
      antibody raised in rabbit against the amino terminus of the rat CB1, we have
      found numerous CB1-like-immunoreactive cells distributed throughout all of the
      pituitary anterior lobe with the exception of the ventrocranial area adjacent to
      the median eminence of the neurohypophysis. Aided by both double-immunostaining
      on consecutive serial sections and double-simultaneous immunofluorescence on the
      same section of the gland, the CB1-like immunoreactivity was compared to some
      specific hormone immunoreactive cells. CB1 labelings were mainly codistributed,
      and even colocalized, with lactotrophs and thyrotrophs. Gonadotrophs containing
      CB1 receptors were also observed. In contrast, corticotrophs, which are located
      mainly in the ventrocranial pole of the anterior lobe, were generally devoid of
      CB1. Since nerve terminals immunoreactive to the CB1 antibody were observed
      within the vascular zone of the median eminence, the possibility that
      endocannabinoids are involved in the control of some secretory activities of
      Xenopus pituitary, either indirectly via hypothalamic neurosecretory mechanisms
      or directly on the pituitary cells, was envisaged. In particular, the present
      study suggests the occurrence of a direct cannabinergic modulation of the
      prolactin, gonadotrophin, and thyrotrophin secretions through the CB1 receptor.

PMID- 11825031
TI  - Cloning and expression of a cDNA for a putative G protein-coupled receptor from
      the hepatopancreas of the crayfish, Procambarus clarkii.
AB  - The authors cloned a novel cDNA encoding a putative G protein-coupled receptor
      (GPCR) from the hepatopancreas of the crayfish, Procambarus clarkii, using a
      screening approach with synthetic oligonucleotides. The oligonucleotides were
      designed homologous to the transmembrane spanning domain III of previously cloned
      receptors from various living organisms. Sequence analysis revealed that one of
      the positive clones contained a cDNA insertion of 3489 bp representing the mRNA
      coding for a part of a putative GPCR (termed HP1R). The clone was truncated at
      the 5' end. The long 3'-untranslated regions (UTR) of 2446 bp contained three
      typical AATAAA censensus sequences for mRNA polyadenylation followed by the
      poly(A) tail at the 3' end. To obtain a full-length cDNA clone, rapid
      amplification of the 5' cDNA ends (5' RACE) technique was then applied. Sequence
      analysis revealed that the full-length cDNA clone had an open-reading frame of
      1116 bp with a 103-bp 5'-UTR. The predicted amino acid sequence of HP1R was 372
      residues long. Hydropathicity analysis of HP1R suggested the presence of seven
      transmembrane domains. The database search revealed that the predicted sequence
      is most closely related to probable GPCR AH9.1 from Caenorhabditis elegans (27%
      identity, 48% homology). In addition, HP1R has lower homologies with receptors
      for somatostatin, opioid, dopamine, adrenalin, and so on. The similarity implied
      that HP1R is a new member of putative GPCRs whose endogenous ligands were
      unknown. In addition, RT-PCR analysis suggested that the transcript was expressed
      predominantly in the hepatopancreas but poorly in the muscle or brain.

PMID- 11825032
TI  - Effect of methyl farnesoate, alone and in combination with other hormones, on
      ovarian growth of the red swamp crayfish, Procambarus clarkii, during
      vitellogenesis.
AB  - The effect of methyl farnesoate (MF) on the ovaries of female red swamp crayfish,
      Procambarus clarkii, undergoing vitellogenesis was determined both in vivo and in
      vitro. The in vivo assay showed a positive effect of MF on oocyte growth when
      injected alone and in combination with 17 beta-estradiol, but not in combination
      with JHIII or 17 alpha-hydroxyprogesterone. A higher level of incorporation of
      labeled leucine was induced by MF on isolated pieces of ovary. The same effect
      was seen when ovary and mandibular organ (MO) were coincubated. These results
      suggest that MF stimulated the synthesis of vitellin in the ovary of crayfish. In
      vitro, 17 alpha-hydroxyprogesterone completely suppressed the stimulatory action
      of the MO on the ovary, suggesting a competitive inhibition between 17 alpha
      hydroxyprogesterone and MF on the ovary and/or a negative feedback by that
      steroid on the MO.

PMID- 11825033
TI  - Rainbow trout eyed-stage embryos demonstrate melatonin rhythms under light-dark
      conditions as measured by a newly developed time-resolved fluoroimmunoassay.
AB  - Melatonin contents in eyed-stage embryos of rainbow trout (Oncorhynchus mykiss)
      were measured by a newly developed, highly sensitive, and nonisotopic immunoassay
      method: time-resolved fluoroimmunoassay (TR-FIA). The melatonin-bovine serum
      albumin (BSA) conjugate was immobilized by physical adsorption to the wells of
      microtiter plates. A competitive assay using two antibodies was performed among
      melatonin-BSA in the solid phase, samples, melatonin antibodies, and europium
      labeled secondary antibodies. The system showed a sensitivity of 0.6 pg/well. The
      embryos showed clear melatonin rhythms under a 12L:12D photo cycle. Although the
      melatonin was detected in the egg yolk, the quantities were the same in both the
      light and dark phases. These results indicate that the melatonin secretion system
      has already functioned at least from the eyed-stage embryo in rainbow trout.

PMID- 11825034
TI  - Thyroid of lake sturgeon, Acipenser fulvescens. I. Hormone levels in blood and
      tissues.
AB  - The authors measured thyroid hormone (TH) levels in plasma, whole carcass, and
      tissues of cultured 2-year-old immature lake sturgeon held in fresh water and in
      serum of adults at spawning time from the Winnipeg River. Circulating thyroxine
      (T4) and 3,5,3'-triiodothyronine (T3) levels were low (T4 approximately 0.3
      ng/ml, T3 approximately 0.2 ng/ml) in all cultured fish and most adults, but a
      few of the latter had exceptionally high T4 and T3 levels. The percentages of
      blood TH found in erythrocytes were 19.5% (T4), 6.1% (T3) and 6.9% (reverse T3 =
      rT3). Equilibrium dialysis showed much higher percentages of plasma free (F) FT4
      (1.1%), FT3 (0.4%), and FrT3 (3,3',5'-triiodothyronine = rT3, 3.0%) for sturgeon
      than for rainbow trout, indicating more limited TH binding to sturgeon plasma
      sites. However, concentrations of FT4 and FT3 were close to those reported for
      salmonids. T3 levels exceeded T4 levels in most extrathyroidal tissues of
      cultured sturgeon but in most cases were less than 0.1 ng/g and 10 to 100 times
      lower than reported for salmonids; only the whole brain T3 concentration (5.6
      ng/g) approached that of salmonids. The digested thyroid contained 21.3 ng T3/g
      and 2.4 ng T4/g. The authors conclude that lake sturgeon have a low circulating
      reserve of bound TH but have FT4 and FT3 concentrations close to those of
      salmonids. The high thyroidal T3:T4 ratio and low tissue T4 levels suggest that,
      in contrast to teleosts studied to date, the thyroid may be a significant direct
      source of T3, the primary TH in sturgeon tissues. High serum T4 and T3 levels in
      some sturgeon at spawning time may suggest a thyroid role in reproduction.

PMID- 11825035
TI  - Thyroid of lake sturgeon, Acipenser fulvescens. II. Deiodination properties,
      distribution, and effects of diet, growth, and a T3 challenge.
AB  - The authors studied the properties and tissue distribution of thyroid hormone
      (TH) deiodination activities measured in vitro at subnanomolar substrate levels
      for cultured 2-year-old lake sturgeon held at 12 to 15 degrees. We also studied
      the deiodination responses to an exogenous 3,5,3'-triiodothyronine (T3) challenge
      and to a diet-induced growth suppression. Thyroxine (T4) outer-ring deiodination
      (T4ORD), T4 inner-ring deiodination (T4IRD), T3IRD, and 3,3',5'-triiodothyronine
      (rT3)ORD activities were evident in liver and intestine. Their properties
      resembled those of teleosts. T3IRD and T4IRD activities predominated in brain.
      Low or negligible deiodination in any form occurred in gill, skeletal muscle,
      kidney, notochord, or immature gonad. Only T4ORD activity was evident in the
      thyroid, suggesting that it secretes some T3. T3ORD and rT3IRD activities were
      undetectable in any tissues. Hepatic T4ORD activity varied during the photophase
      and was highest during late morning. A dietary T3 challenge that doubled plasma
      T3 levels decreased hepatic T4ORD activity without altering any other
      deiodination pathways in liver, intestine, or brain. A diet change from trout
      pellets to ocean zooplankton reduced somatic growth and plasma T3 levels and
      increased hepatic and intestinal T3IRD activities and hepatic rT3ORD activity but
      did not alter hepatic or intestinal T4ORD activity. The authors conclude that
      plasma T3 in lake sturgeon can be derived both from the thyroid and from hepatic
      (and intestinal) T4ORD activity, which varies with sampling time and
      downregulates in response to a T3 challenge. However, a reduction in plasma T3
      accompanying a change in diet and reduced growth was not due to a decrease in
      T4ORD activity; rather, it was due to an increase in hepatic and intestinal T3IRD
      activities. These results suggest a difference in emphasis in thyroidal
      regulation between sturgeon and certain teleosts.

PMID- 11825036
TI  - The nucleotide sequences of the parathyroid gene in primates (suborder
      Anthropoidea).
AB  - Nucleotide sequences of the parathyroid (PTH) gene of 12 species of primates
      belonging to suborder Anthropoidea were examined. The PTH gene contains one
      intron that separates two exons that code the sequence of prepro and PTH,
      respectively. The intron of the PTH gene in Cebus apella, Callithrix jacchus, and
      Saguinus oedipus was 102 bp long, whereas a 103-bp intron was observed in the
      remaining species. Phylogenetic analysis using the nucleotide sequences of PTH
      revealed that these 12 species of primates of suborder Anthropoidea could be
      divided into two groups of the infraorder Platyrrhini (C. apella, C. jacchus, and
      S. oedipus) and the infraorder Catarrhini (Macaca fascicularis, Macaca fuscata,
      Cercopithecus aethiops, Papio hamadryas, Presbytes obscura, Hylobates lar, Pongo
      pygmaeus, Pan troglodytes, and Pan paniscus). The latter infraorder could be
      further subdivided into two subgroups belonging to the superfamily
      Cercopithecoidea (M. fascicularis, M. fuscata, C. aethiops, P. hamadryas, and P.
      obscura) and the superfamily Hominoidea (H. lar, P. pygmaeus, P. troglodytes, and
      P. paniscus). The deduced amino acid sequences of PTH gene between 12 species of
      nonhuman primates and human revealed no amino acid substitution in mature PTH
      among orangutans, chimpanzees, and humans. The results indicated that the PTH
      gene is very conserved among primates, especially between great apes and humans.
      The apes are the most suitable animals to be used for studying the bone
      metabolism and applying the knowledge to clinical use in humans.

PMID- 11825037
TI  - Purification of mummichog (Fundulus heteroclitus) gonadotropins and their
      subunits, using an immunochemical assay with antisera raised against synthetic
      peptides.
AB  - To detect mummichog gonadotropins (GtHs) and their subunits immunochemically,
      fragment peptides with amino acid sequences corresponding to cDNA data were
      synthesized, and antisera were raised against them. In the case of GtH-IIbeta,
      large loops such as the second loop and the "seat belt" structure (deduced from
      the hCG 3D structural data) were considered to be favorable regions for antigen,
      although further examination is needed to determine if this is the case of GtH
      Ibeta and GtH-alpha. In the purification process, glycoprotein was extracted from
      acetone-dried mummichog pituitary and separated by various liquid chromatography
      procedures. Each fraction was assayed by immunoblotting with the appropriate
      antisera against synthetic peptides. Subunits (GtH-alpha, GtH-Ibeta, and GtH
      IIbeta) were obtained through gel filtration, anion-exchange chromatography, and
      reverse-phase HPLC. Intact bioactive GtH-I and GtH-II were obtained through gel
      filtration, anion-exchange chromatography, and hydrophobic chromatography. Both
      GtH-I and GtH-II dissociated into subunits under acidic conditions. Nominal MW of
      each subunit was estimated from SDS-PAGE as 23,000 for GtH-alpha from GtH-I,
      22,000 for GtH-alpha from GtH-II, 18,000 for GtH-Ibeta, and 21,000 for GtH
      IIbeta.

PMID- 11825038
TI  - Developmental profile of thyroid hormone distributor proteins in a marsupial, the
      tammar wallaby Macropus eugenii.
AB  - The ontogeny of thyroxine distributor proteins in serum of the marsupial Macropus
      eugenii (tammar wallaby) was investigated from day 3 after birth until adulthood.
      The thyroxine distributor proteins in the serum of adult M. eugenii are
      transthyretin and albumin. Northern analysis of RNA prepared from liver showed
      that transthyretin mRNA levels were initially high (about adult levels at the
      earliest ages tested), reduced to about 60% adult levels (between days 50 and
      150), and then steadily increased to adult levels (by days 200 to 250). Albumin
      mRNA levels were initially about 50% of adult levels (day 3) and steadily rose to
      90% of adult levels by days 175 to 220. A globulin, "wallaby thyroxine-binding
      protein" (W-TBP), bound [(125)I]thyroxine from day 3 until about day 200. Of the
      protein-bound thyroxine, the proportion bound by transthyretin had a similar
      pattern to the transthyretin mRNA levels. From day 26 onward, about half of the
      protein-bound thyroxine was bound to albumin. On day 3, less than 10% was bound
      to W-TBP and the proportion steadily increased to a maximum of about 46% by about
      day 120 and then reduced to undetectable levels by around day 250. The
      developmentally regulated W-TBP was present throughout pouch life, when the pouch
      young is dependent on obtaining thyroxine required for normal growth and
      development from the mother. After the young tammar wallaby leaves its mother's
      pouch, a time when it has reached a level of physiological development
      approximately equivalent to that at the time of birth in precocious eutherian
      mammals such as cattle and sheep, W-TBP was no longer detected as a thyroxine
      distributor protein in serum.

PMID- 11825039
TI  - Purification, characterization, and biological activity of a substance P-related
      peptide from the gut of the Australian lungfish, Neoceratodus forsteri.
AB  - A peptide with mammalian substance P (SP)-like immunoreactivity was isolated from
      an extract of the spiral intestine of the Australian lungfish, Neoceratodus
      forsteri. The primary structure of this peptide was established as Lys-Pro-Arg
      Pro-Asp-Glu-Phe-Tyr-Gly-Leu-Met . NH2, showing 64% identity with mammalian SP. In
      isolated preparations of lungfish foregut circular muscle, lungfish SP produced a
      slow, long-lasting tonic contraction, with a pD2 value of 8.19. Lungfish midgut
      circular muscle preparations responded to lungfish SP rapidly and in a more
      complex manner. There was an increase in the frequency of spontaneous activity
      (pD2 = 8.76), associated with diminished amplitude of the spontaneous
      contractions (pD2 = 9.24), also coupled in some preparations with a tonic
      contraction (pD2 = 8.43). The response patterns of foregut and midgut circular
      muscle to acetylcholine (ACh) were very similar to those seen to lungfish SP.
      Lungfish SP and ACh, however, had very weak effects on both foregut and midgut
      longitudinal muscle. These data demonstrate that lungfish SP may be a
      physiologically important regulator of gastrointestinal motility in Neoceratodus.
      This study further confirmed that the structures of SP-related peptides have been
      strongly conserved under the pressure of vertebrate evolution, particularly in
      preserving the functionally important sequence, Phe-Xaa-Gly-Leu-Met . amide, at
      the C-terminus. The sequence of lungfish SP is identical to that of bufokinin, a
      SP-related peptide previously isolated from the intestine of the cane toad, Bufo
      marinus, supporting the hypothesis that lungfishes and amphibians share a common
      ancestor.

PMID- 11825041
TI  - Effects of porcine follicle-stimulating hormone on the reproductive performance
      of female zebra finches (Taeniopygia guttata).
AB  - It has been suggested that follicle-stimulating hormone (FSH) may play a role in
      egg size/number trade-offs in oviparous vertebrates. We tested this hypothesis in
      an avian species by administering porcine FSH (pFSH) to intact, captive female
      zebra finches (Taeniopygia guttata) during egg formation. We predicted that (1)
      pFSH would increase the number of ovarian follicles recruited into rapid yolk
      development and so increase clutch size, (2) an increase in clutch size would
      lead to a reduction in egg size, and (3) doses of pFSH that were not sufficient
      to increase clutch size would increase yolk deposition and so increase egg mass.
      Although a range of pFSH doses decreased egg mass by ca. 10% in three separate
      experiments, the reduction in egg mass occurred in the absence of an increase in
      the number of eggs laid. Porcine FSH decreased mean clutch size significantly in
      one experiment and reduced median clutch size significantly in the other two
      experiments. The results of this study did not support the hypothesis that FSH
      mediates a trade-off between egg size and clutch size in birds.

PMID- 11825040
TI  - Plasma concentrations of arginine vasotocin and urotensin II are reduced
      following transfer of the euryhaline flounder (Platichthys flesus) from seawater
      to fresh water.
AB  - Plasma concentrations and stored levels of the neuroendocrine peptides arginine
      vasotocin (AVT) and urotensin II (UII) were measured in the euryhaline flounder
      (Platichthys flesus) following the acute hypo-osmotic challenge of direct
      seawater (SW) to fresh water (FW) transfer. Hormone measures, plasma osmolality,
      and ion concentrations and tissue water content were determined 1, 4, 8, 24, 72,
      and 144 h after transfer. Plasma AVT concentration fell initially following FW
      transfer but then returned toward pretransfer levels by day 6. Plasma UII
      concentration decreased while urophysial UII content was increased following hypo
      osmotic challenge relative to SW time-matched controls, suggesting down
      regulation of the UII system during the initial stages after FW transfer. These
      changes in neuroendocrine activity were associated with a significant fall in
      plasma osmolality and major plasma ions. Positive correlations were observed
      between plasma AVT and osmolality and Cl- and Mg2+ concentrations, suggesting
      functional association of these plasma parameters with AVT action and/or control
      of AVT secretion. The initial response to hypotonic challenge involves reduced
      plasma AVT and UII levels consistent with the proposed role for these hormones,
      supporting flounder osmoregulation in hypertonic media.

PMID- 11825042
TI  - Cell proliferation and apoptosis in the anterior pituitary of chicken during
      inhibition and resumption of laying.
AB  - The goal of this study was to determine whether tissue rejuvenation of the
      anterior pituitary with cell proliferation and apoptosis occurs during inhibition
      and resumption of egg-laying. White Leghorn laying hens were subjected to
      inhibition of laying by feed withdrawal. Feeding was resumed on the fourth day of
      egg-laying cessation. All birds were injected ip with bromodeoxyuridine (BrdU) 1
      h before tissue collection. The anterior pituitary glands were collected from
      hens of the following groups: pretreatment (PT), 3 and 5 days after starvation
      (3DS and 5DS, respectively), 3 days after cessation of laying (3DC), 10 days
      after cessation of laying (10DC, 6 days after resumption of feeding), and the day
      of and 1 week after resumption of laying (RL and 1WRL, respectively). They were
      processed for the detection of proliferating cells and apoptotic cells by BrdU
      immunostaining and terminal deoxynucleotidyl transferase-mediated biotinylated
      deoxyuridine triphosphate nick-end-labeling (TUNEL). Immunostaining for the
      anterior pituitary hormones was also conducted. In the cephalic lobe the BrdU
      positive cells showed a higher frequency in RL than in PT, 3DC, and 1WRL. BrdU
      positive cell frequency in the caudal lobe was greater in RL than in PT. TUNEL
      positive cells in both cephalic and caudal lobes were increased markedly in the
      RL group. Their frequency in the cephalic lobe was greater in RL than in PT, and
      that in the caudal lobe of RL was higher than in any other group of birds. The
      areas of FSH-like cells in 10DC and RL were greater than those in PT to 3DC, and
      those of LH-like cells in RL were greater than those of 3DS to 3DC. PRL-like
      cells were decreased until 3DC and then gradually increased until 1WRL. GH-, TSH
      , and ACTH-like cell areas showed tendencies to increase until 3DC, with
      decreasing thereafter. The sizes of FSH-like cells in 10DC to 1WRL and LH-like
      cells in RL were larger than those around cessation of laying. These results
      suggest that during inhibition and resumption of laying cell proliferation and
      apoptosis occur in the anterior pituitary tissue, which may cause a rejuvenation
      of tissue to improve the function of this organ.

PMID- 11825043
TI  - Differential expression and cellular localization of activin and inhibin mRNA in
      the rainbow trout ovary and testis.
AB  - An inhibin cDNA from rainbow trout consisted of 1305 bp, which coded for 352
      amino acid residues. The deduced amino acid sequence of mature inhibin was 50 to
      60% identical to mammalian sequences. Distribution of inhibin alpha and activin
      beta A and beta B in different ovarian and testis compartments was studied in
      rainbow trout by in situ hybridization with complementary RNA probes. In testis
      tissue, inhibin alpha and activin beta A and beta B were expressed only in the
      testicular interstitia between the seminal lobules, where Sertoli cells and
      Leydig cells are distributed. The localizations and intensities of the reactions
      were constant throughout the maturation of the testis. Within ovarian tissue, the
      theca cell layers of follicles showed strong reactions of Dig-labeled antisense
      mRNA probes hybridizing against inhibin alpha and activin beta A and beta B in
      all samples over the same sampling period. In regressing oocytes, a positive
      reaction was observed in the granular cell layer of the follicles.

PMID- 11825044
TI  - Surveillance and control of blood-borne virus infections in haemodialysis units.
AB  - The risk of transmission of blood-borne viruses in renal dialysis units was
      reduced following the Rosenheim report recommendations issued in 1972. This
      document focused on the prevention and control of hepatitis B virus infections in
      renal dialysis and transplantation units. Good practice guidelines were produced,
      some of which may have been relaxed in conjunction with technological advances
      which included the use of disposable cartridges for haemodialysis. However, new
      viruses transmitted by blood and other body fluids have been identified over the
      years. A review of current practice for both patients and staff, together with
      updated good practice guidance, is necessary.

PMID- 11825045
TI  - Viral hepatitis in South African healthcare workers at increased risk of
      occupational exposure to blood-borne viruses.
AB  - The prevalence of hepatitis A, B and C antibodies was measured in a group of
      healthcare workers (HCWs) at increased risk of occupational acquisition of blood
      borne viruses (N=402) from a large, urban referral hospital in South Africa. The
      aims of this study were to determine the immunity of HCWs to these agents and to
      recommend policy for the protection of HCWs against occupational exposure to
      viral hepatitis in this country. Race, sex and age were shown to be important
      factors influencing the presence of hepatitis A (HAV) antibodies. Most black HCWs
      (96.2%) are protected from HAV infection. Females have significantly higher HAV
      antibodies compared with males and antibodies increase with increasing age.
      Hepatitis B antibodies (anti-HBs) were found in 30.6% of HCWs. Anti-HBs levels
      were significantly associated with a past history of HBV vaccination. However,
      only a small proportion of HCWs (21.2%) could remember ever being immunized
      against HBV. For those individuals that did receive HBV vaccination (N=83), the
      mean number of years since their last vaccine was 6.2 years (SD +/- 3.5). HCV
      antibodies were found in 1.8% of HCWs at increased risk of occupational exposure.
      It was not possible to define whether these infections were occupationally
      acquired but genotyping of the HCV (in two of seven cases) showed genotype 5, the
      predominant South African genotype. New recommendations for the prevention of
      viral hepatitis in HCWs in South Africa are made, including pre-employment
      screening for HAV based on self-selection criteria, universal anti-HBs screening
      with HBV booster vaccination. HCV recommendations are based on appropriate
      education of HCWs about this infection and its prevention and a standardized post
      exposure testing protocol.

PMID- 11825046
TI  - Incidence of nosocomial rotavirus infections, symptomatic and asymptomatic, in
      breast-fed and non-breast-fed infants.
AB  - Rotavirus is one of the most important aetiological agents of nosocomial
      infections in childhood. We studied the incidence of nosocomial rotavirus
      infections in 420 patients (age range 1-18 months) consecutively admitted from 1
      December 1999 to 31 May 2000 to the infant ward of the Department of Paediatrics,
      University of Turin. We also evaluated the protective effect of breast feeding.
      Faecal specimens were collected from every child (whether developing diarrhoeic
      symptoms or not) and tested for rotavirus during hospitalization and 72 h after
      discharge. The incidence of rotavirus nosocomial infections was 27.7%. The
      incidence of symptomatic nosocomial infections was 16.8%, and the incidence of
      asymptomatic infections was 10.9%. The attack rate of the infections that
      occurred during hospitalization was 11.8%, while for those occurring after
      discharge, it was 15.9%. Rotavirus infection, on average, prolonged hospital stay
      from 5.2 to 6.4 days. 10.6% of breast-fed infants and 32.4% of non-breast-fed
      infants contracted rotavirus infection (P<0.005). None of the breast-fed infants
      who contracted rotavirus infection developed diarrhoeic symptoms.

PMID- 11825047
TI  - Spread of methicillin-resistant Staphylococcus aureus in a neonatal intensive
      unit associated with understaffing, overcrowding and mixing of patients.
AB  - Over the period May-June 1999, an outbreak of methicillin-resistant
      Staphylococcus aureus (MRSA) was registered in eight newborns in a neonatal
      intensive care unit (NICU) at the Department of Pediatrics, Ulleval University
      Hospital (UUH) in Oslo. Seven were infected or colonized with an
      indistinguishable strain, detected at the NICU, and one patient with a slightly
      different PFGE type (i.e. a subtype) was registered at the outpatient clinic. The
      MRSA strains resembled the sensitive, inbred 'Norwegian type' described four
      years earlier at UUH, showing a relatively low and heterogenic methicillin
      resistance (MIC 12-96 mg/L), and susceptibility to most other anti-staphylococcal
      agents. Before and during the outbreak, there was high activity, understaffing,
      overcrowding and a mix of patients; 42% of the staff were relatively untrained,
      and up to 62% (during weekends) were extra nursing staff, partly from other
      Scandinavian countries. All cases were isolated (air and contact isolation), and
      all other patients and personnel were treated as being exposed to MRSA (isolated
      from other departments) until the last patient had been identified, disinfection
      of all rooms was complete, and all screening samples from staff and other
      patients were negative. The NICU and the delivery suite were closed for one week
      for disinfection and screening. The outbreak ended after 34 days. Since then, two
      years later, no further cases have been detected in the NICU or the delivery
      suite.

PMID- 11825048
TI  - The Nottingham Staphylococcus aureus population study: prevalence of MRSA among
      the elderly in a university hospital.
AB  - A prevalence survey of methicillin-resistant Staphylococcus aureus (MRSA) in
      elderly patients (65 years and older) three weeks after admission to a university
      hospital was performed. Risk factors associated with hospital MRSA carriage were
      determined. The design was a cross-sectional patient-based study and all adult
      wards at the University Hospital Nottingham (1600 beds) were included. Three
      hundred and forty-two elderly individuals (65 years and older) were enrolled into
      the study on day 21 after admission. One hundred and twenty patients [35.08% (95%
      confidence intervals 29.93-40.25%)] carried S. aureus. MRSA was isolated from 54
      patients. The MRSA prevalence was 158/1000 (95% CI 119-197/1000 patients).
      Independent risk factors for MRSA carriage in the hospital were exposure to
      ampicillin [adjusted odds ratio 4.1 (95% CI 1.28-13.14)] and ciprofloxacin [17.1
      (95% CI 2.91-99.90)]. Forty-one MRSA isolates (75.9%) belonged to the epidemic
      type EMRSA 15, seven isolates to EMRSA 16 (12.9%) and six isolates were sporadic
      strains as determined by genetic typing. It can be expected that among this
      defined risk group, between 187 and 331 patients carried MRSA on discharge in the
      year 2000. MRSA carriage is frequent and detected in only 15% of actual carriers
      amongst elderly patients by routine clinical investigations three weeks after
      admission. The only significant risk factor identified by multivariate logistic
      regression was antibiotic chemotherapy. The repeated finding of a strong
      association between MRSA colonization and previous ciprofloxacin exposure demands
      attention and indicates that fluoroquinolones should be used prudently in
      institutions where MRSA is endemic.

PMID- 11825049
TI  - Evaluation of bedmaking-related airborne and surface methicillin-resistant
      Staphylococcus aureus contamination.
AB  - The number of airborne methicillin-resistant Staphylococcus aureus (MRSA) before,
      during and after bedmaking was investigated. Air was sampled with an Andersen air
      sampler in the rooms of 13 inpatients with MRSA infection or colonization.
      Sampling of surfaces, including floors and bedsheets, was performed by stamp
      methods. MRSA-containing particles were isolated on all the sampler stages-stage
      1 (>7 microm diameter) to stage 6 (0.65-1.1 microm). The MRSA-containing
      particles were mostly 2-3 microm diameter before bedmaking and >5 microm during
      bedmaking. The number was significantly higher 15 min after bedmaking than during
      the resting period, but the differences in counts after 30 and 60 min were not
      significant. MRSA was detected on many surfaces. The results suggest that MRSA
      was recirculated in the air, especially after movement. To prevent airborne
      transmission, healthcare staff should exercise great care to disinfect inanimate
      environments. Further studies will be needed to confirm the level of MRSA
      contamination of air during bedmaking and establish measures for prevention of
      airborne transmission.

PMID- 11825050
TI  - Handwashing frequencies in an intensive care unit.
AB  - As most nosocomial infections are thought to be transmitted by the hands of
      healthcare workers, handwashing is considered the single most important
      intervention to prevent nosocomial infections. However, previous studies have
      shown that handwashing practices are poor, especially among medical personnel.
      The objective of this study was to assess the rate of handwashing among intensive
      care unit (ICU) healthcare personnel, and then to propose realistic suggestions
      so that hand hygiene' could be performed at an optimal level. To achieve this,
      each healthcare worker in the ICU of Istanbul Medical Faculty was observed
      directly, and, a comprehensive microbiological investigation was carried out
      among personnel and of the inanimate environment. The frequency of handwashing
      was low; 12.9% among medical personnel. Moreover, there was a widespread
      contamination in the ICU and 28.1% of the healthcare workers were carriers for
      methicillin-resistant Staphylococcus aureus (MRSA). The factors that contributed
      to low compliance of handwashing protocols were: a low staff to patient ratio,
      excessive use of gloves and deficiencies in the infra-structure of ICU. In heavy
      workload conditions, alcoholic handrub solutions for quick hand decontamination
      can be considered as an alternative to handwashing.

PMID- 11825051
TI  - Marketing hand hygiene in hospitals--a case study.
AB  - Hand hygiene of healthcare workers is frequently poor despite the efforts of
      infection control teams to promote hand decontamination as the most important
      method to prevent transmission of hospital-acquired infections. In this case
      study, we describe how principles of societal marketing were applied to improve
      hand hygiene. Pre-marketing analysis of strengths, weaknesses, opportunities and
      threats to implementation; attention to product, price, promotion and placement;
      and post-marketing 'customer' surveys were the essential components of the
      marketing strategy and its implementation. Placement of an alcohol-based gel
      decontaminant (Spirigel) at the bedside of every patient was widely welcomed in
      the hospital, and has played a major role in improving hand hygiene of healthcare
      workers. In the twelve months following the implementation, the decontaminant was
      used at least 440,000 times. The cost of purchasing the decontaminant was
      approximately 5000 pounds sterling. Following the introduction of Spirigel, there
      was a consistent reduction in the proportion of hospital-acquired methicillin
      resistant Staphylococcus aureus (MRSA) in each of the quarters of 2000-2001
      compared with 1999-2000. In the period 1999-2000, nearly 50% of the MRSA were
      hospital acquired compared with 39% in 2000-2001. Similarly, the average
      incidence of Clostridium difficile associated diarrhoea (CDAD) decreased in each
      of the quarters in 2000-2001 following the introduction of Spirigel. During this
      period, there was an average incidence of 9.5 cases of CDAD/1000 admissions
      compared with 11.5 cases of CDAD/1000 admissions in 1999-2000. This represents a
      17.4% reduction in the incidence of CDAD. However, this reduction was not
      statistically significant (P=0.2). Our case study demonstrates that principles of
      societal marketing methods can be used effectively to promote and sustain hand
      hygiene in hospitals. Improvement in hand hygiene will lead to considerable
      reduction in hospital-acquired infections.

PMID- 11825052
TI  - Trends in bacteraemia on the haematology and oncology units of a UK tertiary
      referral hospital.
AB  - As part of ongoing surveillance of infection in the haematology and oncology
      units at Belfast City Hospital, microbiologically documented bloodstream
      infections over three 12-month periods 1994/5, 1998/9 and 1999/00 were reviewed.
      Gram-positive organisms were the most common cause of blood stream infection in
      the haematology unit causing 66%, 56% and 64% of episodes of monomicrobial
      bacteraemia in 1994/5, 1998/9 and 1999/00, respectively. In haematology patients,
      enterococci have emerged as an important cause of bacteraemia, with increasing
      levels of glycopeptide resistance, and the 'non-fermenting Gram-negative rods
      other than Pseudomonas aeruginosa' are an increasingly common cause of
      monomicrobial and polymicrobial bacteraemia. In oncology patients, Gram-negative
      organisms (predominantly enterobacteriaceae) were more common than Gram-positive
      organisms, causing 50% and 54% of monomicrobial bacteraemia in 1998/9 and
      1999/00, respectively. Changes in patient population, underlying diseases and
      chemotherapeutic agents may explain these findings. The spectrum of infection
      seen in haematology and oncology patients changes as management evolves. Ongoing
      co-operation between haematologists, oncologists and microbiologists is important
      to detect trends in epidemiology, which can be used to design empirical
      antibiotic regimens and guide infection control policies.

PMID- 11825053
TI  - Increase in prevalence of nosocomial non-Candida albicans candidaemia and the
      association of Candida krusei with fluconazole use.
AB  - Candida is an important nosocomial pathogen. This study was undertaken to provide
      information on the rate of candidaemia, to define the risks for candidaemia and
      to describe and account for the epidemiology of candidaemia at our institution
      between 1992 and 1999. The overall rate was 0.052 per 1000 patient days and 0.27
      per 1000 discharges. The major risks for candidaemia were colonization at a non
      sterile site (OR 3.85, 95%CI 1.80-9.09), total parenteral nutrition (TPN) in the
      absence of neutropenia (OR 11.8, 95%CI 4.5-35.4, P<0.001) and neutropenia in the
      absence of TPN (OR 3.7, 95%CI 1.8-7.7, P<0.001). There was no change in the
      overall incidence of candidaemia but there was a steady decline in the rate of C.
      albicans with a corresponding rise in the incidence of non- C. albicans species.
      C. krusei was highly associated with fluconazole exposure (chi(2)=20.78,
      P<0.001). There was no evidence of spread of C. krusei using random amplification
      of polymorphic DNA, suggesting the appearance of this organism was due to the
      selection pressure exerted by fluconazole.

PMID- 11825054
TI  - Testing chemical germicides against Candida species using quantitative carrier
      and fingerpad methods.
AB  - Six disinfectants were tested against Candida albicans, C. parapsilosis and C.
      tropicalis using quantitative carrier tests based on glass (QCT-1) and metal (QCT
      2) surfaces. C. albicans was also used to test four topical agents by a fingerpad
      method. Hard water (200 ppm as CaCO(3)) was the product diluent. In preliminary
      tests with QCT-1 and QCT-2, the testing was with or without a soil load;
      subsequent tests and fingerpad tests included soil. In QCT-1 and QCT-2, each
      carrier received 10 microL (5.0 x 10(6) - 1.0 x 10(7)colony forming units) of
      Candida, and was air dried for 1 h, then exposed to 1 mL or 50 microL of test
      product at 22 +/- 2 degrees C for up to 10 min. Controls received an equivalent
      volume of saline. For fingerpad tests, each digit received 10 microL of inoculum,
      which was allowed to dry and exposed to 1 mL of test product for 20 s. Inoculated
      plates of Sabouraud's dextrose agar were held for 48 h at 30 degrees C and
      colonies counted to determine reductions in colony forming units. In tests on
      both hard surfaces and fingerpads, ethanol and products based on ethanol reliably
      and rapidly inactivated all the Candida species tested. Products with sufficient
      potency to have tuberculocidal claims produced substantial reductions in the
      titre of C. albicans, although some showed a lesser reduction in titre of C.
      tropicalis and C. parapsilosis. This may reflect differences in cell
      hydrophobicity between Candida species, and highlights the need for care in
      selecting a suitable surrogate for disinfectant tests. The quantitative carrier
      and fingerpad protocols are suitable for assessing the activity of disinfectants
      and topical antiseptics against candida.

PMID- 11825056
TI  - Needleless connectors--the way forward in the prevention of catheter-related
      infections?

PMID- 11825057
TI  - An outbreak of vancomycin-resistant enterococci associated with major ward
      refurbishment.

PMID- 11825058
TI  - Methicillin-resistant Staphylococcus aureus and healthcare associated infection
      surveillance.

PMID- 11825059
TI  - Global and gene-specific methylation patterns in cancer: aspects of tumor biology
      and clinical potential.
AB  - Heritable alterations of DNA that do not affect the base pair sequence itself but
      nevertheless regulate the predetermined activity of genes are referred to as
      epigenetic. Epigenetic mechanisms comprise diverse phenomena including stable
      feedback loops, nuclear compartmentalization, differential replication timing,
      heritable chromatin structures, and, foremost, DNA cytosine methylation (1-3).
      DNA cytosine methylation has recently gained major attention in the field of
      basic molecular biology as well as in studies of human diseases including cancer.
      Changes in DNA methylation patterns in human malignancies have been shown to
      contribute to carcinogenesis in multiple ways. Both hypo- and hypermethylation
      events have been described in various neoplasias leading to chromosomal
      instability and transcriptional gene silencing. DNA methylation research has
      entered the clinical arena and methylation patterns have become a major focus of
      clinicians seeking novel prognostic factors and therapeutic targets. The
      following minireview covers aspects of the basic molecular biology of DNA
      methylation and summarizes its importance in human cancers.

PMID- 11825060
TI  - Molecular mechanisms of thyroid hormone effects on bone growth and function.

PMID- 11825061
TI  - Granulin precursor gene: a sex steroid-inducible gene involved in sexual
      differentiation of the rat brain.
AB  - The mechanisms of sexual differentiation of the brain by sex steroids seem to be
      conserved throughout the mammalian species, although there may be some species
      differences. In rats, sex-dependent differentiation of the brain occurs in a sex
      steroid-dependent manner during the perinatal period known as the critical
      period. Androgen exposure during the perinatal period results in the development
      of structural and functional sexually dimorphic characteristics in the brain; the
      absence of testicular androgen leads the central nervous system to develop
      passively in a primarily female fashion, while the presence of androgen induces
      the masculinization of the brain. We attempted to characterize sex steroid
      inducible genes that are involved in the sexually dimorphic function of the
      brain. Following the cDNA subtraction between hypothalami of 5-day-old intact and
      neonatally androgenized female rats, a granulin (grn) precursor gene was
      identified. The grn gene encodes a 6-kDa polypeptide known as a growth modulating
      factor of epithelial cells in vitro. Exogenous estrogen, as well as androgen,
      induced grn gene expression in the neonatal hypothalamus. In the brain of a 5-day
      old male rat, grn mRNA was expressed in the ventromedial hypothalamic nucleus and
      the arcuate nucleus of the hypothalamus. Throughout the critical period for
      sexual differentiation of the brain, grn gene expression remained high in males,
      while in females it gradually decreased. Antisense oligodeoxynucleotide (ODN)
      complementary to grn mRNA was synthesized and infused into the third ventricle of
      male rats at 2 days of age. Two different control treatments were used; the first
      consisted of a control sequence ODN that had virtually no homology to known
      mRNAs, and the second consisted of vehicle alone. After maturation, the subject
      animals that were treated with antisense ODN of grn displayed significantly lower
      scores than the control males in various parameters assessing sexual behavior,
      i.e., mount, intromission, and ejaculation. The present results suggest that the
      grn gene, the expression of which is induced by sex steroids in the neonatal
      hypothalamus, plays a crucial role in the functional masculinization of the rat
      brain.

PMID- 11825062
TI  - Long-term therapy with NTBC and tyrosine-restricted diet in a murine model of
      hereditary tyrosinemia type I.
AB  - In human patients with hereditary tyrosinemia type I (HT1) a combination therapy
      of 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3 cyclohexane dione (NTBC) and dietary
      restriction of phenylalanine and tyrosine is currently widely used. We previously
      reported that the use of NTBC in a murine model of HT1 abolished acute liver
      failure but did not prevent the development of hepatocellular carcinoma (HCC) in
      the setting of nonrestricted protein intake. Here we present the results obtained
      with higher doses of NTBC plus dietary tyrosine restriction on long-term follow
      up (>2 years). Liver function tests and succinylacetone levels were completely
      corrected with this regimen and cancer-free survival was improved when compared
      to historical controls. However, while no HT1 animals had HCC at age 13 months,
      the incidence was 2/16 (13%) at age 18 months and 1/6 (17%) after 24 months.
      Thus, even the most stringent therapy could not prevent the emergence of HCC in
      the mouse model of HT1, even when initiated prenatally.

PMID- 11825063
TI  - Correlation among genotype, phenotype, and biochemical markers in Gaucher
      disease: implications for the prediction of disease severity.
AB  - Gaucher disease is a lysosomal storage disorder characterized by a deficiency of
      the enzyme acid beta-glucosidase. The clinical manifestations of Gaucher disease
      are highly variable, and although certain genotypes are often associated with
      mild or severe symptoms, a defined correlation between genotype and phenotype
      does not exist. Identification of biochemical markers characteristic of pathology
      may be of use in predicting the progression of the disease state. In this study
      the relationship among genotype, glycolipid substrates, lysosomal proteins, and
      the clinical manifestations of Gaucher disease has been evaluated. Plasma
      glycolipids were analyzed using electrospray ionization-tandem mass spectrometry.
      Lysosomal-associated membrane protein-1 (LAMP-1) and saposin C were determined by
      immunoquantification. Patients with Gaucher disease were shown to have an
      increased 16:0-glucosylceramide/16:0-lactosylceramide ratio and elevated
      concentrations of LAMP-1 and saposin C in plasma. A general relationship was
      found to exist among the 16:0-glucosylceramide/16:0-lactosylceramide ratio, LAMP
      1 and saposin C levels, and patient phenotype, providing a refinement of the
      genotype-phenotype correlation. These findings have major implications for the
      diagnosis, prediction of disease severity, and monitoring of therapy in patients
      with Gaucher disease.

PMID- 11825064
TI  - Urinary glycosaminoglycan excretion quantified by an automated semimicro method
      in specimens conveniently transported from around the globe.
AB  - Current and future treatments for children with mucopolysaccharidosis (MPS)
      diseases require early, presymptomatic diagnosis, yet existing diagnostic methods
      to quantitate urinary glycosaminoglycan (GAG) are labor-intensive, and thus not
      applicable for newborn screening. Direct and rapid quantification of GAG
      excretion with 1,9-dimethylmethylene blue (DMB) is applicable to small volumes of
      urine collected, dried, and mailed on a paper matrix (MPS Test). To determine if
      this assay could be automated, a robotic instrument was programmed to accomplish
      the procedure; the pilot method simultaneously determined GAG and creatinine
      concentrations in 10 patient specimens/run. Each analyte is measured in 4
      dilutions, thus increasing the operating range to cover a broad spectrum of
      normal and pathologic levels. Samples and reagents are mixed in a 96-well tray
      format in approximately 20 min, and densitometric measurements are recorded in
      less than 60 s. Optical density measurements are electronically transmitted to a
      desktop computer to select optimal dilutions, identify values above or below the
      level of reliability, make calculations, and print reports. This automated method
      was applied to 255 specimens from 101 subjects representing each of the MPS
      diseases--specifically, types I (n = 126), II (n = 47), III (n = 48), IV (n =
      17), VI (n = 14) and VII (n = 3). This method discriminated pathologic elevations
      of GAG excretion of MPS patients particularly when multiple specimens were
      available. Patients with non-MPS lysosomal diseases had normal GAG excretion,
      except for a patient with fucosidosis who had markedly elevated levels.
      Automation of the direct DMB method provides the key technology necessary for
      newborn screening for MPS diseases.

PMID- 11825065
TI  - Lactase gene transcription is activated in response to hypoxia in intestinal
      epithelial cells.
AB  - Lactase-phlorizin hydrolase, a brush-border membrane disaccharidase, is a marker
      of intestinal epithelial cell differentiation and digestive function. The
      intestine is susceptible to conditions of hypoxia resulting from vascular
      perfusion deficits. We hypothesized that lactase gene induction may provide a
      mechanism to efficiently increase nutrient energy substrates during gut hypoxia.
      These studies sought to characterize expression of the lactase gene in response
      to hypoxia and to characterize a role for hypoxia-inducible factor (HIF-1) in
      mediating the hypoxic response. Microarray analysis and confirmatory RT-PCR
      identified a 4-fold induction of lactase mRNA abundance in intestinal epithelial
      Caco-2 cells exposed to hypoxia. Lactase promoter activity was similarly induced
      by hypoxia in cells stably transfected with a 2.0-kb 5' flanking region of the
      rat lactase gene linked to a reporter gene. Transient cotransfection with HIF
      1alpha and beta stimulated lactase promoter activity 2.4- and 3.5-fold under
      conditions of normoxia and hypoxia, respectively. We conclude that HIF-1 can
      activate the lactase promoter in intestinal epithelial cells exposed to hypoxia.
      Induction of lactase transcription may represent an adaptive response to gut
      hypoxia.

PMID- 11825066
TI  - Outcome of the first 3-years of a DNA-based neonatal screening program for
      glutaric acidemia type 1 in Manitoba and northwestern Ontario, Canada.
AB  - Glutaric acidemia type 1 (GA1) is overrepresented in the aboriginal population of
      Island Lake, Manitoba, and northwestern Ontario who speak the Ojibway-Cree (Oji
      Cree) dialect. The carrier frequency in these communities has been predicted to
      be as high as 1 in 10 individuals. Prior to beginning newborn screening for GA1
      in May 1998, 18 of 20 affected patients diagnosed at this center have been from
      these high-risk communities. Most have followed an acute encephalopathic course
      with permanent neurologic sequelae and high mortality. They excrete small amounts
      of glutaric acid and 3-hydroxyglutaric acid and have significant residual enzyme
      activity. A single homozygous mutation in glutaryl-CoA-dehydrogenase (GCDH IVS-1
      + 5g right arrow t) has been identified in this population. DNA-based newborn
      screening targeted to our high-risk communities was begun in order to provide
      presymptomatic detection and treatment of affected patients. Of the first 1176
      newborns screened, 4 affected infants were identified and treated with a low
      protein diet, carnitine, and riboflavin. All 4 infants have required numerous
      hospitalizations for treatment of intercurrent illnesses. Eventually, 3 infants
      presented with acute dystonic encephalopathy and seizures along with permanent
      neurological sequelae. One of these infants died unexpectedly at home at 18
      months of age. The fourth, now 9 months old, has had a gastrostomy tube placed to
      facilitate fluid replacement in addition to a standard treatment protocol and is
      doing well. The reasons for our initial disappointing outcomes in the first 3 of
      4 affected babies are likely multiple. Based on our early experience and that of
      other centers screening newborns for GA1, current therapeutic strategies may be
      insufficient in preventing the occurrence of neurologic sequelae in some
      children. An incomplete understanding of the neurotoxic mechanisms underlying
      this devastating disorder hampers effective management.

PMID- 11825068
TI  - DNA-based diagnosis of isolated sulfite oxidase deficiency by denaturing high
      performance liquid chromatography.
AB  - Isolated sulfite oxidase deficiency is a rare autosomal recessive disease,
      characterized by severe neurological abnormalities, seizures, mental retardation,
      and dislocation of the ocular lenses, that often leads to death in infancy. There
      is a special demand for prenatal diagnosis, since no effective treatment is
      available for isolated sulfite oxidase deficiency. Until now, the cDNA sequence
      of the sulfite oxidase (SUOX) gene has been available, but the genomic sequence
      of the SUOX gene has not been published. In this study, we have performed a DNA
      based diagnosis of isolated sulfite oxidase deficiency in a Chinese patient. To
      do so, we designed oligonucleotide primers for amplification of the predicted
      exons and intron-exon boundaries of the SUOX gene obtained from the completed
      draft version of the human genome. Using overlapping PCR products, we confirmed
      the flanking intronic sequences of the coding exons and that the entire 466
      residue mature peptide is encoded by the last exon of the gene. We then performed
      mutation detection using denaturing high-performance liquid chromatography
      (DHPLC). The DHPLC chromatogram of exon 2b showed the presence of heteroduplex
      peaks only after mixing of the mutant DNA with the wild-type DNA, indicating the
      presence of a homozygous mutation. Direct DNA sequencing showed a homozygous base
      substitution at codon 160, changing the codon from CGG to CAG, which changes the
      amino acid from arginine to glutamine, i.e., R160Q. The DNA-based diagnosis of
      isolated sulfite oxidase deficiency will enable us to make an accurate
      determination of carrier status and to perform prenatal diagnosis of this
      disease. The availability of the genomic sequences of human genes from the
      completed draft human genome sequence will simplify the development of molecular
      genetic diagnoses of human diseases from peripheral blood DNA.

PMID- 11825067
TI  - Evidence of common ancestry for the maple syrup urine disease (MSUD) Y438N allele
      in non-Mennonite MSUD patients.
AB  - Maple syrup urine disease (MSUD) is a rare (1/185,000) autosomal recessive inborn
      error of branched-chain amino acid metabolism characterized by increased plasma
      leucine, isoleucine, and valine levels. Though, genetically heterogeneous in the
      worldwide population, MSUD in Old Order Mennonites (1/150-176) is the result of a
      tyrosine to asparagine substitution (Y438N; previously Y393N) in the E1alpha
      subunit of the branched-chain alpha-keto acid dehydrogenase (BCKAD) complex. Due
      to endogamous practices, the presence of Y438N in all reported Mennonite MSUD
      patients has historically been attributed to a founder effect. However, we have
      also identified the Y438N defect in eight MSUD patients of non-Mennonite lineage.
      To evaluate the genetic origin of this defect in these non-Mennonite patients, we
      examined Mennonite MSUD families and non-Mennonite MSUD families using
      microsatellite markers located on chromosome 19q13.1-13.2 (location of E1alpha
      gene, BCKDHA). Haplotype analyses revealed a major and four minor haplotypes that
      cosegregate with the Y438N allele in the Old Order Mennonite MSUD patients and
      carrier relatives. Analyses of eight non-Mennonite MSUD patients reveal that
      three of the non-Mennonite MSUD patients shared common Mennonite Y438N
      haplotypes, strongly suggesting Mennonite ancestry. However, the remaining non
      Mennonite patients carry Y438N haplotypes that are significantly different from
      the Mennonite Y438N haplotype, suggesting that the occurrence of the defect in
      these families is due to either pre-Mennonite or de novo events.

PMID- 11825069
TI  - Synthesis and structure of [PPh(4)](3)[Cr(Te(4))(3)].DMF: the first
      tris(tetratelluride) complex.
AB  - The compound [PPh(4)](3)[Cr(Te(4))(3)].DMF has been synthesized from the reaction
      of Cr(CO)(6) with a polytelluride solution in dimethylformamide at 100 degrees C.
      The compound has been characterized by (125)Te NMR and single-crystal X-ray
      diffraction techniques. The compound crystallizes in the triclinic space group P(
      )1, with a = 12.991(3) A, b = 14.782(3) A, c = 24.628(5) A, alpha= 90.63(3)o,
      beta= 104.45(3)o, gamma= 106.49(3)o, and Z = 2 (T = 153 K). The [Cr(Te(4))(3)](3
      ) anion consists of a Cr(III) center chelated by three Te(4)(2-) ligands in a
      distorted octahedral environment. The anion has the Deltalambdalambdalambda (or
      Lambdadeltadeltadelta) conformation.

PMID- 11825070
TI  - Novel acetate polyoxomolybdate "host" accommodating a zigzag-chainlike "guest" of
      five edge-shared sodium cations:
      Na(21)[[Na(5)(H(2)O)(14)]within[Mo(46)O(134)(OH)(10)(mu
      CH(3)COO)(4)]].CH(3)COONa. approximately equal to 95H(2)O.
AB  - A novel ESR-silent polyoxomolybdate
      Na(21)([Na(5)(H(2)O)(14)][Mo(46)O(134)(OH)(10)(mu
      CH(3)COO)(4)]).CH(3)COONa.approximately equal to 90H(2)O (3) was simply
      synthesized in high yield by reducing an acidified aqueous solution of
      Na(2)MoO(4).2H(2)O and CH(3)COONa.3H(2)O. The structure of 3 is constructed by a
      46-member crown-shaped anion,
      [Na(5)(H(2)O)(14)]within[Mo(V)(20)Mo(VI)(26)O(134)(OH)(10)(mu-CH(3)COO)(4)](21-),
      3a, which is built up by three different but related building blocks in a new
      mode and further connected into layers via Na(+) and hydrogen bonds. Crystal data
      of compound 3: triclinic space group P(-1); a = 16.4065(3), b = 17.4236(2), c =
      20.8247(3) A; alpha= 87.57, beta= 67.9810(10), gamma= 80.6970(10)o; V =
      5445.08(14) A(3); Z = 1; D(calcd) = 2.902. Structure solution and refinement are
      based on 19014 reflections, R = 0.0750.

PMID- 11825071
TI  - Growth of Sb(2)E(3) (E = S, Se) polygonal tubular crystals via a novel solvent
      relief-self-seeding process.
AB  - A novel solvent-relief-self-seeding (SRSS) process was applied to grow bulk
      polygonal tubular single crystals of Sb(2)E(3) (E = S, Se), using SbCl(3) and
      chalcogen elements E (E = S, Se) as the raw materials at 180 degrees C for 7 days
      in ethanol solution. The products were characterized by various techniques,
      including X-ray powder diffraction (XRD), scanning electronic microscope (SEM),
      transmission electronic microscope (TEM), electronic diffraction (ED), and X-ray
      photoelectron spectra (XPS). The calculated electrical resistivities of the
      tubular single crystals in the range 20-320 K were of the order of 10(5)-10(6)
      Omega cm for Sb(2)S(3) and 10(3)-10(4) Omega cm for Sb(2)Se(3), respectively. The
      studies of the optical properties revealed that the materials formed had a band
      gap of 1.72 eV for Sb(2)S(3) and 1.82 eV for Sb(2)Se(3), respectively. The
      optimal reaction conditions for the growth of bulk tubular single crystals were
      that the temperature was not lower than 180 degrees C and the reaction time was
      not shorter than 7 days. The possible growth mechanism of tubular crystals was
      also discussed.

PMID- 11825072
TI  - Polar effects in nitride coupling reactions.
AB  - The nucleophilic molybdenum nitride (Et(2)NCS(2))(3)MoN (1) reacts with the
      electrophilic osmium nitride complex TpOsNCl(2) (2, Tp = hydrotris(1
      pyrazolyl)borate) to produce molecular nitrogen. Reaction of 1 at the nitride is
      accompanied by a substantial amount of reaction at a sulfur atom of the
      dithiocarbamate ligand, forming the osmium thionitrosyl complex TpOs(NS)Cl(2)
      (4). Labeling experiments establish that the N(2) produced comes specifically
      (>96%) from mixed-metal (molybdenum-osmium) coupling. The major transition-metal
      containing product of the reaction is the mu-nitrido complex TpOsCl(2)(mu
      N)Mo(S(2)CNEt(2))(3) (3), where the bridging nitride derives primarily (82%) from
      the osmium nitride 2. The mu-nitrido complex 3 has been characterized
      crystallographically, and shows a nitride bridge that is very asymmetric (Mo-N =
      1.721(3) A, Os-N = 1.906(3) A), with less multiple bonding toward osmium and more
      toward molybdenum. Heterometallic coupling is much faster than either
      homometallic coupling reaction, in particular the osmium-osmium coupling, despite
      the greater oxidizing power of osmium over molybdenum. The origin and
      implications of this kinetic effect on nitride coupling and dinitrogen cleavage
      are discussed.

PMID- 11825073
TI  - X-ray structures of the first platinum complexes with Z configuration iminoether
      ligands: trans-dichlorobis(1-imino-1-methoxy-2,2'-dimethylpropane)platinum(II)
      and trans-tetrachlorobis(1-imino-1-methoxy-2,2'-dimethylpropane)platinum(IV).
AB  - Platinum complexes with Z configuration iminoether ligands (trans
      [PtCl(2)(HN=C(OMe)Bu(t))(2)], 1, and trans-[PtCl(4)(HN=C(OMe)Bu(t))(2)], 2) have
      been structurally characterized for the first time. The nearly planar Pt-N-C-O-C
      chain, all atoms being in gauche conformation, brings the terminal Pt and C atoms
      very close to one another. The steric clash is released by considerably
      increasing the Pt-N-C, N-C-O, and C-O-C bond angles (133, 124, and 121 degrees
      for 1, respectively; 147, 129, and 127 degrees for 2, respectively), which are
      well above the expected values (120 degrees for Pt-N-C and N-C-O; less than 120
      degrees for C-O-C owing to the repulsive effect exerted by the lone pair of
      electrons on the oxygen atom). In the platinum(II) case the smaller increase of
      bond angles is accompanied by a greater value of the Pt-N-C-O torsion angle (27.3
      and 15.6 degrees for 1 and 2, respectively). The stabilization of the Z
      configuration, notwithstanding the steric clashes described above, has been
      achieved by a careful choice of the R substituent in the iminoether moiety (a
      bulky tert-butyl group). The reactions of the platinum(IV) species (2) in basic
      and acidic conditions and with triphenylphosphine have been investigated. Bases
      and acids both interact with the coordinated ligand in such a way to weaken the
      coordinative bond and promote the release of the iminoether ligands. The
      phosphine promotes a ready and complete reduction of the platinum(IV) complex to
      the corresponding platinum(II) species (1). Compound 1 reacts with a
      stoichiometric amount of phosphine (1:1 molar ratio) to form cis
      [PtCl(2)(PPh(3))(Z-HN=C(OMe)Bu(t))] and with excess phosphine to form
      [PtCl(2)(PPh(3))(2)] and free iminoether. The latter two reactions leading to
      formation of a mixed phosphine/iminoether platinum species and to free
      iminoether, which can be used as a synthon for further organic transformations,
      can be of synthetic utility.

PMID- 11825075
TI  - Chalcogen-rich lanthanide clusters: compounds with Te(2-), (TeTe)(2-), TePh,
      TeTePh, (TeTeTe(Ph)TeTe)(5-), and [(TeTe)(4)TePh](9-) ligands; single source
      precursors to solid-state lanthanide tellurides.
AB  - Lanthanide metals react with PhTeTePh and elemental Te in pyridine to give
      (py)(y)Ln(4)(Te)(TeTe)(2)(TeTeTe(Ph)TeTe)(Te(x)TePh) (Ln = Sm (y = 9; x = 0); Tb,
      Ho (y = 8, x = 0.1)), and (py)(7)Tm(4)(Te)[(TeTe)(4)TePh](Te(0.6)TePh) clusters.
      The Sm, Tb, and Ho compounds contain a square array of Ln(III) ions all connected
      to a central Te(2-) ligand. Two adjacent edges of the square are bridged by
      ditelluride ligands, with the Ln ion that is eta(2) bound to both of these TeTe
      ligands also coordinating to a terminal TePh ligand. The other two edges of the
      square are spanned by ditellurides that both coordinate a TePh ligand that has
      been displaced from the Ln ion by pyridine, to give the pentaanion (mu-eta(2)
      eta(2)-Te(2)Te(Ph)Te(2)).(5-) In the Tm compound, the displaced TePh interacts
      with all four TeTe units. The compounds are air-, light-, and temperature
      sensitive. Upon thermolysis, they decompose to give solid-state TbTe(2-x), HoTe,
      or TmTe, with elimination of Te and TePh(2).

PMID- 11825074
TI  - Dicopper(II) complexes of H-BPMP-type ligands: pH-induced changes of redox,
      spectroscopic ((19)F NMR studies of fluorinated complexes), structural
      properties, and catecholase activities.
AB  - Substitution of the methyl group from the H-BPMP (HL(CH)3) ligand (2,6-bis[(bis(2
      pyridylmethyl)amino)methyl]-4-methylphenol) by electron withdrawing (F or CF(3))
      or electron donating (OCH(3)) groups afforded a series of dinucleating ligand
      (HL(OCH)3, HL(F), HL(CF)3), allowing one to understand the changes in the
      properties of the corresponding dicopper complexes. Dinuclear Cu(II) complexes
      have been synthesized and characterized by spectroscopic (UV-vis, EPR, (1)H NMR)
      as well as electrochemical techniques and, in some cases, by single-crystal X-ray
      diffraction: [Cu(2)(L(OCH)3)(muOH)][(ClO(4))(2)].C(4)H(8)O,
      [Cu(2)(L(F))(muOH)][(ClO(4))(2)], [Cu(2)(L(F))(H(2)O)(2)][(ClO(4))(3)].C(3)D(6)O,
      and [Cu(2)(L(CF)3)(H(2)O)(2)][(ClO(4))(3)].4H(2)O. Significant differences are
      observed for the Cu-Cu distance in the two mu-hydroxo complexes (2.980 A (R =
      OCH(3)) and 2.967 A (R = F)) compared to the two bis aqua complexes (4.084 A (R =
      F) and 4.222 A (R = CF(3))). The mu-hydroxo and bis aqua complexes are reversibly
      interconverted upon acid/base titration. In basic medium, new species are
      reversibly formed and identified as the bis hydroxo complexes except for the
      complex from HL(CF)3 which is irreversibly transformed near pH = 10. pH-driven
      interconversions have been studied by UV-vis, EPR, and (1)H NMR, and the
      corresponding pK are determinated. In addition, with the fluorinated complexes,
      the changes in the coordination sphere around the copper centers and in their
      redox states are evidenced by the fluorine chemical shift changes ((19)F NMR).
      For all the complexes described here, investigations of the catechol oxidase
      activities (oxidation of 3,5-di-tert-butylcatechol to the corresponding quinone)
      are of interest in modeling the catecholase enzyme active site and in
      understanding aspects of structure/reactivity. These studies show the pH
      dependence for the catalytic abilities of the complexes, related with changes in
      the coordination sphere of the metal centers: only the mu-hydroxo complexes from
      HL(CH)3, HL(F), and HL(OCH)3 exhibit a catecholase activity. Modification on R
      substituent induces a drastic effect on the catecholase activity: the presence of
      an electron donating group on the ligand increases this activity; the reverse
      effect is observed with an electron withdrawing group.

PMID- 11825076
TI  - A coordination polymer of cobalt(II)-glutarate: two-dimensional interlocking
      structure by dicarboxylate ligands with two different conformations.
AB  - A novel Co-glutarate, Co[O(2)C(CH(2))(3)CO(2)] (1), was synthesized as single
      crystals by the hydrothermal reaction of CoCl(2) with glutaric acid in the
      presence of KOH and characterized by single-crystal X-ray diffraction analysis,
      TGA, IR, UV-vis reflectance spectrometry, and SQUID measurements. The dark purple
      Co-glutarate crystallizes in the monoclinic system in the space group P2/c, with
      a = 14.002(3) A, b = 4.8064(10) A, c = 9.274(3) A, beta = 90.5(2)degrees, and Z =
      4. The Co(2+) centers are tetrahedrally coordinated to four oxygen atoms from the
      dicarboxylate ligands. The anhydrous-pillared three-dimensional structure
      consists of infinite Co-CO(2)-Co inorganic layers, which are stacked by the
      coordinated glutarate alkyl chain along the a-axis. There are two different
      conformations for glutarate ligands, i.e., the gauche- and the anti-forms. These
      ligands reside between the inorganic layers alternatively to separate each layer
      by 7.01 A (gauche) and 6.99 A (anti). Magnetic measurement reveals that the
      predominant magnetic interactions are antiferromagnetic below 14 K.

PMID- 11825077
TI  - Syntheses, structures, and properties of trinuclear complexes
      [M(bpca)(2)(M'(hfac)(2))(2)], constructed with the complexed bridging ligand
      [M(bpca)(2)] [M, M' = Ni(II), Mn(II); Cu(II), Mn(II); Fe(II), Mn(II); Ni(II),
      Fe(II); and Fe(II), Fe(II); Hbpca = Bis(2-pyridylcarbonyl)amine, Hhfac =
      Hexafluoroacetylacetone].
AB  - Five trinuclear complexes [M(bpca)(2)(M'(hfac)(2))(2)] (where MM'(2) = NiMn(2),
      CuMn(2), FeMn(2), NiFe(2), and FeFe(2); Hbpca = bis(2-pyridylcarbonyl)amine; and
      Hhfac = hexafluoroacetylacetone) were synthesized almost quantitatively by the
      reaction of [M(bpca)(2)] and [M'(hfac)(2)] in 1:2 molar ratio, and their
      structures and magnetic properties were investigated. Three complexes, with M' =
      Mn, crystallize in the same space group, Pna2(1), whereas two complexes, with M'
      = Fe, crystallize in P4(1), and complexes within each set are isostructural to
      one another. In all complexes, [M(bpca)(2)] acts as a bis-bidentate bridging
      ligand to form a linear trinuclear complex in which three metal ions are arranged
      in the manner M'-M-M'. The central metal ion is in a strong ligand field created
      by the N(6) donor set, and hence the Fe(II) in the [Fe(bpca)(2)] moiety is in a
      low-spin state. The terminal metal ions (M') are surrounded by O(6) donor sets
      with a moderate ligand field, which leads to the high-spin configuration of
      Fe(II). Three metal ions in all complexes are almost collinear, and metal-metal
      distances are ca. 5.5 A. The magnetic behavior of NiMn(2) and NiFe(2) shows a
      weak ferromagnetic interaction between the central Ni(II) ion and the terminal
      Mn(II) or Fe(II) ions. In these complexes, sigma-spin orbitals of the central
      Ni(II) ion and those of terminal metal ions have different symmetry about a 2
      fold rotation axis through the Ni-N(amide)-M'(terminal) atoms, and this results
      in orthogonality between the neighboring sigma-spin orbitals and thus
      ferromagnetic interactions.

PMID- 11825078
TI  - Trithiotungsten(VI) complexes having phosphine-thiolate hybrid ligands: synthesis
      and cluster forming reactions with CuBr, FeCl(2), and
      [Fe(CH(3)CN)(6)](ClO(4))(2).
AB  - Five-coordinated trithiotungsten complexes (PPh(4))[(dmsp)W(S)(3)] (1a) and
      (PPh(4))[(dpsp)W(S)(3)] (1b) (R(2)PCH(2)CH(2)S(-); R = Me (dmsp-)), Ph (dpsp-)))
      were synthesized by addition of Hdmsp and Hdpsp to a THF solution of
      (PPh(4))[(EtS)W(S)(3)]. Treatment of 1a with CuBr in the presence of PPh(3) in
      CH(3)CN afforded a WCu(2) cluster (dmsp)WS(3)Cu(2)(PPh(3))(2)Br (2). The reaction
      of 1a with 1 equiv of FeCl(2) went smoothly to generate a 1:1 adduct
      (PPh(4))[(dmsp)WS(3)(FeCl(2))] (3), while 3 did not react further with excess
      FeCl(2). On the other hand, 3 was found to react with
      [Fe(CH(3)CN)(6)](ClO(4))(2), giving rise to an unusual tetranuclear cluster,
      [(dmsp)WS(3)](2)Fe(2)Cl (4), while the reaction of 1a with 2 equiv of
      [Fe(CH(3)CN)(6)](ClO(4))(2) led to a cyclic octanuclear cluster
      [(dmsp)WS(3)Fe](4) (5). Although the oxidation states of W(VI), Cu(I), and Fe(II)
      are retained in 2 and 3, reduction of the metal ions occurs in the formation of 4
      and 5. All the complexes reported in this paper were structurally characterized
      by X-ray analysis. It is anticipated that the new type of trithiotungsten
      complexes, 1a and 1b, will serve as potential synthons for various heterometallic
      sulfide clusters.

PMID- 11825080
TI  - On the resonance energy in new all-metal aromatic molecules.
AB  - We have recently advanced the aromaticity concept into all-metal molecules
      containing Al(4)(2-), XAl(3)(-), Ga(4)(2-), In(4)(2-), Hg(4)(6-), Al(3)(-), and
      Ga(3)(-) aromatic units. All these systems are electron deficient species
      compared to the corresponding aromatic hydrocarbons. The electron deficiency
      results in an interesting new feature in all-metal aromatic systems, which should
      be considered as having both pi- and sigma-aromaticity, and that should result in
      their additional stability. In this work, we obtain crude evaluations of the
      resonance energies for Na(2)Al(4) and Na(2)Ga(4) all-metal aromatic molecules.
      The resonance energies were found to be unusually high: 30 kcal/mol (B3LYP/6
      311+G*) and 48 kcal/mol (CCSD(T)/6-311+G(2df)) for Na(2)Al(4) and 21 kcal/mol
      (B3LYP/6-311+G*) for Na(2)Ga(4) compared to 20 kcal/mol in benzene. We believe
      that the high resonance energies in Na(2)Al(4) and in Na(2)Ga(4) are due to the
      presence of three completely delocalized bonds, one pi-bond and two sigma-bonds,
      thus confirming the presence of pi- and sigma-aromaticity.

PMID- 11825079
TI  - Sterically hindered carboxylate ligands support water-bridged dimetallic centers
      that model features of metallohydrolase active sites.
AB  - The synthesis and characterization of carboxylate-bridged dimetallic complexes
      are described. By using m-terphenyl-derived carboxylate ligands, a series of
      dicobalt(II), dicobalt(III), dinickel(II), and dizinc(II) complexes were
      synthesized. The compounds are [Co(2)(mu-O(2)CAr(Tol))(2)(O(2)CAr(Tol))(2)L(2)]
      (1), [Co(2)(mu-OH(2))(2)(mu-O(2)CAr(Tol))(2)(O(2)CAr(Tol))(2)L(2)] (2a-c),
      [Co(2)(mu-OH)(2)(mu-O(2)CAr(Tol))(2)(O(2)CAr(Tol))(2)L(2)] (3), [Ni(2)(mu
      O(2)CAr(Tol))(4)L(2)] (4), [Ni(2)(mu-HO...H)(2)(mu
      O(2)CAr(Tol))(2)(O(2)CAr(Tol))(2)L(2)] (5), and [Zn(2)(mu
      O(2)CAr(Tol))(2)(O(2)CAr(Tol))(2)L(2)] (6), where Ar(Tol)CO(2)H = 2,6-di(p
      tolyl)benzoic acid and L = pyridine, THF, or N,N-dibenzylethylenediamine.
      Structural analysis of these complexes revealed that additional bridging ligands
      can be readily accommodated within the [M(2)(mu-O(2)CAr(Tol))(2)](2+) core,
      allowing a wide distribution of M...M distances from 2.5745(6) to 4.0169(9) A.
      Unprecedented bridging units [M(2)(mu-OH(2))(2)(mu-O(2)CR)(2)](n+) and [M(2)(mu
      HO...H)(2)(mu-O(2)CR)(2)](n+) were identified in 2a-c and 5, respectively, in
      which strong hydrogen bonding accommodates shifts of protons from bridging water
      molecules toward the dangling oxygen atoms of terminal monodentate carboxylate
      groups. Such a proton shift along the O...H...O coordinate attenuates the donor
      ability of the anionic carboxylate ligand, which can translate into increased
      Lewis acidity at the metal centers. Such double activation of bridging water
      molecules by a Lewis acidic metal center and a metal-bound general base may
      facilitate the reactivity of metallohydrolases such as methionine aminopeptidase
      (MAP).

PMID- 11825081
TI  - Zr(11)Sb(18): a new binary antimonide exhibiting an unusual Sb atom network with
      nonclassical Sb-Sb bonding.
AB  - The herewith-introduced antimonides Zr(11)Sb(18) and Zr(10.4)V(0.6)Sb(18) were
      prepared by high-temperature techniques; both arc-melting and solid-state
      reactions at 1200 degrees C starting from alpha-ZrSb(2) and the metals Zr and V
      in powder form are possible methods. These isostructural compounds represent an
      unprecedented metal:antimony ratio of 11:18 and form a new structure type.
      Zr(11)Sb(18) crystallizes in the tetragonal space group I(-)42d, with the lattice
      dimensions a = 676.94(4) pm and c = 6007.3(5) pm, while the V-containing phase
      forms a slightly smaller unit cell with a = 676.48(8) pm and c = 6005.6(9) pm (Z
      = 4). Their structures are comprised of an Sb atom substructure with several
      intermediate Sb-Sb bonds starting at 311 pm, which is reminiscent of that found
      in the series (Ti,M)(5)Sb(8) (M = Zr, Hf, Nb, Mo) published last year. Interwoven
      with this network is the Zr atom network, which forms a diamond-like metal atom
      substructure with long Zr-Zr contacts of ca. 360 pm. Band structure calculations
      based on the linear muffin tin orbital approach reveal these antimonides to be
      mainly stabilized by strong M-Sb and intermediate Sb-Sb bonds, and additionally-
      to the smallest extent--by M-M bonds (M = Zr, V). In agreement with the
      electronic structure calculations, Zr(11)Sb(18) is metallic with a small positive
      Seebeck coefficient.

PMID- 11825082
TI  - Modification of second-sphere communication, leading to an unusually high
      abundance of the head-to-head conformer of cisplatin cross-link retro models.
AB  - Rapid atropisomerization of cisplatin-DNA cross-link models, cis-PtA(2)G(2) (A(2)
      = two amines or a diamine, G = guanine derivative, bold font indicating a guanine
      not linked to another guanine), makes their NMR spectra uninformative. The
      conformers [two head-to-tail (DeltaHT and LambdaHT) conformers, one head-to-head
      (HH) conformer] are detected in (CCC)PtG(2) retro models (CCC = chirality
      controlling chelates designed to reduce rotation around the G N7 to Pt bond by
      destabilizing the transition state). Clear trends are found with four CCC
      ligands, 2,2'-bipiperidine (Bip) and N,N'-dimethyl-2,3-diaminobutane (each with
      S,R,R,S and R,S,S,R configurations at the chelate ring N, C, C, and N atoms,
      respectively). S,R,R,S ligands favor left-handed G base canting and the LambdaHT
      form; R,S,S,R ligands favor right-handed canting and the DeltaHT form. The HH
      conformer is normally negligible unless G = 5'-GMP. However, understanding this
      5'-phosphate effect is complicated by possible interligand interactions of the 5'
      phosphate with the N1H of the cis-5'-GMP and a CCC NH; these interactions are
      referred to as second-sphere (SSC) and first-to-second-sphere (FSC)
      communication, respectively. We now investigate the four (CCC)PtG(2) models with
      1-Me-5'-GMP, a G lacking the N1H needed for SSC. The phosphate location makes FSC
      possible in the major but not the minor HT form. The major form should increase
      from pH 3 to pH 7 because the phosphate is deprotonated at pH 7. However, the
      major DeltaHT form for the R,S,S,R pair did not change in abundance, and the
      major LambdaHT form for the S,R,R,S pair actually decreased. Thus, FSC is weak.
      At pH approximately 7 the HH conformer of the S,R,R,S pair had an abundance (40
      44%) higher than that in any reported cis-PtA(2)G(2) adduct. FSC involving one 1
      Me-5'-GMP could play a role. The high HH abundance and use of a pH jump
      experiment with (S,R,R,S)-BipPt(1-Me-5'-GMP)(2) allowed us to obtain the first
      deconvoluted CD spectrum for a cis-PtA(2)G(2) HH conformer. The CD features for
      the HH conformer are much weaker than for the HT conformers. Our findings are
      best interpreted to indicate that FSC is not important in aqueous solution,
      especially for the HT form. Weak FSC is consistent with recent models of the
      cross-link in duplexes. In contrast, crystals of fluxional models often reveal
      FSC, but not the more important SSC. SSC was unrecognized until our retro model
      studies, and the new results reinforce the value of studying retro models for
      identifying interactions in solution.

PMID- 11825083
TI  - Ligand-tetrahydrofuran coupling in chelated aluminum phosphinates.
AB  - When the reagents LAlMe (L = N,N'-(alkylene or arylene)bis(3,5-di-tert
      butyl)salicylideneimine (alkylene = ethylene (Salen(tBu))(1), propylene
      (Salpen(tBu))(2), and butylene (Salben(tBu)) (3); arylene = phenylene
      (Salophen(tBu) (4), 3,4-dimethylphenylene (Salomphen(tBu) (5)) are combined with
      Ph(H)P(O)OH in tetrahydrofuran (thf) the unique aluminophosphinate compounds,
      [L(tBu)Al[O(2)P(H)Ph]](n) with L, n = Salen,(infinity)(6), Salpen, 2 (7), Salben,
      2 (8), Salophen, (infinity)(9) and Salomphen, (infinity)(10) are produced. The
      yields for the latter two reactions are low, and it was subsequently found that
      the unique thf-coupled compounds appear in the thf filtrates of the original
      reaction mixture. These compounds are, [L-thf(tBu)Al[O(2)P(H)Ph]](2), L =
      Salophen (13) and Salomphen (14). The thf connects through an alpha-carbon to
      only one of the two possible imine carbons of the ligand. While trying to
      determine how this coupling proceeds, the six-coordinate, solution-state species
      LAlMe(thf) (L = Salophen (11) and Salomphen (12) were discovered and implicated
      as intermediates. All of the compounds are characterized by melting point, NMR,
      IR, and X-ray analyses for 5-8, 13, and 14. A possible mechanism for the thf
      coupling event is presented.

PMID- 11825084
TI  - Synthesis, excited-state dynamics, and reactivity of a directly-linked
      pyromellitimide-(porphinato)zinc(II) complex.
AB  - N-[5-(10,20-Diphenylporphinato)zinc(II)]-N'-(octyl)pyromellitic diimide (PZn-PI),
      a meso-pyromellitimide-substituted (porphinato)zinc(II) compound, has been
      fabricated from the reaction of (5-amino-10,20-diphenylporphinato)zinc(II) with
      pyromellitic dianhydride in the presence of octylamine. Interrogation of the
      photoinduced charge separation (CS) and thermal charge recombination (CR)
      electron-transfer (ET) dynamics for PZn-PI in CH(2)Cl(2) via pump-probe transient
      absorption spectroscopic methods shows that tau(CS) and tau(CR) are 770 and 5200
      fs, respectively. These ET dynamics differ from those elucidated previously for
      closely related 5-quinonyl-substituted (porphinato)metal compounds, and derive
      from the fact that the low-lying excited states for PZn-PI are porphyrin
      localized, possessing little charge-transfer character. The synthesis of N-(5-[15
      (2-(triisopropylsilyl)ethynyl)-10,20-diphenylporphinato]zinc(II))-N'
      (octyl)pyromellitic diimide demonstrates that PZn-PI can be halogenated at its 15
      meso-position and used subsequently as a substrate in metal-catalyzed cross
      coupling reactions; the reactivity of PZn-PI is unusual with respect to many
      directly linked donor-acceptor compounds in that it is stable to these oxidizing
      and reducing reaction conditions.

PMID- 11825085
TI  - Transition-metal complexes of a bifunctional tetradentate gallium alkoxide
      ligand.
AB  - The mixed gallium transition-metal complexes [FeCl[Ga(2)((t)Bu)(4)(neol)(2)]] (1)
      and [M[Ga(2)((t)Bu)(4)(neol)(2)]], M = Co (2), Ni (3), Cu (4), have been prepared
      by the reaction of [Ga(2)((t)Bu)(4)(neol-H)(2)] (neol-H(2) = 2,2-dimethyl-propane
      1,3-diol) with the appropriate metal halide and Proton Sponge. Compounds 1-4 have
      been characterized by NMR (3), UV/vis, and IR spectroscopy and magnetic
      susceptibility (solution and solid state), and their molecular structures have
      been confirmed by X-ray crystallography. The molecular structure of compounds 1-4
      consists of a tetracyclic core formed from two four-membered and two six-membered
      rings. The central metal atom adopts a square pyramidal (1) or square planar (2
      4) geometry. The magnetic susceptibilities for 1, 2, and 4 are as expected for
      strong ligand field environments. On the basis of spectroscopic and structural
      data, the [Ga(2)((t)Bu)(4)(neol)(2)](2-) ligand appears to be more flexible than
      other chelating ligands; this is proposed to be due to the flexibility in the O
      Ga-O bond angle.

PMID- 11825086
TI  - Synthesis, structure, and theoretical study of the nonclassical [CuTe(7)](3-)
      anion.
AB  - The compound [PPh(4)](2)[NEt(4)][CuTe(7)] has been synthesized from the reaction
      of CuCl with a polytelluride solution in dimethylformamide at room temperature.
      The compound crystallizes with two formula units in the triclinic space group P(
      )1 in a cell with dimensions a = 8.9507(18) A, b = 14.714(3) A, and c = 23.277(5)
      A and alpha= 86.32(3) degrees, beta= 80.17(3) degrees, and gamma= 75.63(3)
      degrees (T = -120 degrees C). Ab initio calculations indicate that the
      nonclassical [CuTe(7)](3)(-) anion is the result of joining Te(3)(2-) and
      [CuTe(4)](1-) fragments through donor-acceptor interactions.

PMID- 11825087
TI  - Coordination-position isomeric M(II)Cu(II) and Cu(II)M(II) (M = Co, Ni, Zn)
      complexes derived from macrocyclic compartmental ligands.
AB  - The dinucleating macrocyclic ligands (L(2;2))(2-) and (L(2;3))(2-), comprised of
      two 2-[(N-methylamino)methyl]-6-(iminomethyl)-4-bromophenolate entities combined
      by the -(CH(2))(2)- chain between the two aminic nitrogen atoms and by the 
      (CH(2))(2)- or -(CH(2))(3)- chain between the two iminic nitrogen atoms, have
      afforded the following M(II)Cu(II) complexes: [CoCu(L(2;2))](ClO(4))(2).MeCN
      (1A), [NiCu(L(2;2))](ClO(4))(2) (2A), [ZnCu(L(2;2))](ClO(4))(2).0.5MeCN.EtOH
      (3A), [CoCu(L(2;3))(MeCN)(2-PrOH)](ClO(4))(2) (4A), [NiCu(L(2;3))](ClO(4))(2)
      (5A), and [ZnCu(L(2;3))](ClO(4))(2).1.5DMF (6A).
      [CoCu(L(2;2))(MeCN)(3)](ClO(4))(2) (1A') crystallizes in the monoclinic space
      group P2(1)/n, a = 11.691(2) A, b = 18.572(3) A, c = 17.058(3) A, beta= 91.18(2)
      degrees, V = 3703(1) A(3), and Z = 4. [NiCu(L(2;2))(DMF)(2)](ClO(4))(2) (2A')
      crystallizes in the triclinic space group P(-)1, a = 11.260(2) A, b = 16.359(6)
      A, c = 10.853(4) A, alpha= 96.98(3) degrees, beta= 91.18(2) degrees, gamma=
      75.20(2) degrees, V = 1917(1) A(3), and Z = 2. 4A crystallizes in the monoclinic
      space group P2(1)/c, a = 15.064(8) A, b = 11.434(5) A, c = 21.352(5) A, beta=
      95.83(2)degrees, V = 3659(2) A(3), and Z = 4. The X-ray crystallographic results
      demonstrate the M(II) to reside in the N(amine)(2)O(2) site and the Cu(II) in the
      N(imine)(2)O(2) site. The complexes 1-6 are regarded to be isomeric with
      [CuCo(L(2;2)))](ClO(4))(2).DMF (1B), [CuNi(L(2;2)))](ClO(4))(2).DMF.MeOH (2B),
      [CuZn(L(2;2)))](ClO(4))(2).H(2)O (3B)), [CuCo(L(2;3)))](ClO(4))(2).2H(2)O (4B),
      [CuNi(L(2;3)))](ClO(4))(2) (5B), and [CuZn(L(2;3)))](ClO(4))(2).H(2)O (6B)
      reported previously, when we ignore exogenous donating and solvating molecules.
      The isomeric M(II)Cu(II) and Cu(II)M(II) complexes are differentiated by X-ray
      structural, magnetic, visible spectroscopic, and electrochemical studies. The two
      isomeric forms are significantly stabilized by the "macrocyclic effect" of the
      ligands, but 1A is converted into 1B on an electrode, and 2A is converted into 2B
      at elevated temperature.

PMID- 11825088
TI  - Synthesis and thermolysis of alkyl- and phenylamido diphenylgallium,
      [Ph(2)GaN(H)R](2). isolation and structural characterization of (PhGaNMe)(7) and
      (PhGaNPh)(4).
AB  - Alkyl- and phenylamido diphenylgallium compounds, [Ph(2)GaN(H)R](2) (R = Me, 1;
      Et, 2; (n)Pr, 3; (i)Bu, 4; Ph, 5), were prepared from the reactions of Ph(3)Ga
      with the corresponding primary amines and aniline at elevated temperatures and
      were characterized by elemental analysis, mass spectroscopy, and (1)H NMR and IR
      spectroscopy. These dimeric compounds contained bridging amido groups and
      exhibited both trans and cis isomers in solution. Thermolysis of compounds 1 and
      5 was carried out either without solvent or in dodecane solutions, and two
      clusters, (PhGaNMe)(7) 6 and (PhGaNPh)(4) 7, were isolated in 24% and 55% yields
      and characterized. The structure of 6 consisted of a heptameric Ga(7)N(7) core
      constructed with Ga(2)N(2) and Ga(3)N(3) rings, and the structure of 7 possessed
      a Ga(4)N(4) cubane core.

PMID- 11825089
TI  - Synthesis and characterization of the "sulfur-rich"
      bis(perthiobenzoato)(dithiobenzoato)technetium(III) heterocomplex.

PMID- 11825090
TI  - Preferential C-binding versus N-binding in imidazole depends on the metal
      fragment involved.

PMID- 11825091
TI  - A study on the novel d-f heterodinuclear Gd(III)-Ni(II) cryptate: synthesis,
      crystal structure, and magnetic behavior.

PMID- 11825092
TI  - Oxidative addition of N-H bonds to a metal center: synthesis, characterization,
      and crystal structure of new rhodium(III) hydrido-pyrazolate complexes.

PMID- 11825093
TI  - Using pharmacokinetic-pharmacodynamic relationships to predict the effect of poor
      compliance.
AB  - Since it is difficult to improve patient compliance to drug prescriptions, an
      alternative is to select a drug with less consequences for poor compliance, that
      is, a drug that has the capacity of 'forgiveness'. Forgiveness is the property of
      a drug which, when compared with another medicine with different pharmacokinetics
      and/or concentration-effect relationships, blunts the consequences of missing one
      or two doses in a row, or has a greater variability in the timing of intake.
      Simulations show that drugs with a concentration-effect relationship modelled
      with an effect compartment, for example a delayed response, have more
      forgiveness. A marker of forgiveness would be of some help for doctors deciding
      which drug to prescribe to patients who are poor compliers.

PMID- 11825094
TI  - Clinical pharmacokinetics of candesartan.
AB  - Candesartan cilexetil is the prodrug of candesartan, an angiotensin II type 1
      (AT1) receptor antagonist. Absorbed candesartan cilexetil is completely
      metabolised to candesartan. Oral bioavailability is low (about 40%) because of
      incomplete absorption. Plasma protein binding in humans is more than 99%. The
      volume of distribution in healthy individuals is 0.13 L/kg. CV-15959 is the
      inactive metabolite of candesartan. Candesartan that reaches the systemic
      circulation is mainly cleared by the kidneys, and to a smaller extent by the
      biliary or intestinal route. The apparent oral clearance of candesartan is 0.25
      L/h/kg after a single dose in healthy individuals. Oral clearance (3.4 to 28.4
      L/h) is highly variable among patients. No relevant pharmacokinetic drug-food or
      drug-drug interactions are known. The terminal elimination half-life remains
      unclear, but appears to be longer than the currently used range of 4 to 9 hours.
      Non-compartmental models do not appear to be appropriate for the analysis of
      candesartan pharmacokinetic data. A 2-compartment analysis revealed a much longer
      half-life of 29 hours using data from patients with hypertension. However, a
      further indepth analysis has never been performed. The concentration-effect
      relationship is unaffected by age. No gender or race differences have been shown
      in the effect or pharmacokinetics of candesartan. Renal function affects the
      pharmacokinetic profile of candesartan. For patients with creatinine clearances
      of >60 ml/min x 1.73m(2), 30 to 60 ml/min x 1.73m(2) and 15 to 30 ml/min x
      1.73m(2), the elimination half-life is 7.1, 10.0 and 15.7 hours, respectively, at
      a dose of 8 mg/day. However, at 12 mg/day an accumulation factor of 1.71 was
      found. Thus, a maximum daily dose of up to 8mg appears suitable in patients with
      severe renal dysfunction. No significant elimination of candesartan occurs with
      haemodialysis. In patients with mild to moderate hepatic impairment, no relevant
      pharmacokinetic alterations have been observed. Dosages of up to 12 mg/day do not
      require precautions in patients with mild to moderate liver disease. Clinically
      effective dosages range between 8 and 32 mg/day. The response rate of monotherapy
      with candesartan in patients with hypertension increases with dosage, but never
      exceeds 60% at a daily dosage of 16mg of candesartan. Dosages up to 32 mg/day do
      not increase this response rate.

PMID- 11825095
TI  - Clinical pharmacokinetics of salmeterol.
AB  - Salmeterol is an inhaled long-acting selective beta(2)-adrenoceptor agonist that
      is commercially available as the xinafoate (1-hydroxy-2-naphthoic acid) salt of
      the racemic mixture of the two optical isomers, (R)- and (S)-, of salmeterol. It
      acts locally in the lung through action on beta2 receptors. Limited data have
      been published on the pharmacokinetics of salmeterol. Moreover, there are no data
      on the extent to which inhaled salmeterol undergoes first-pass metabolism. This
      lack of information is most likely due to the very low plasma concentrations
      reached after inhalation of therapeutic doses of salmeterol and the problems in
      developing an analytical method that is sensitive enough to determine these
      concentrations. When salmeterol is inhaled, plasma concentrations of the drug
      often cannot be detected, even at 30 minutes after administration of therapeutic
      doses. Larger inhaled doses give approximately proportionally increased blood
      concentrations. Plasma salmeterol concentrations of 0.1 to 0.2 and 1 to 2
      microg/L have been attained in healthy volunteers about 5 to 15 minutes after
      inhalation of a single dose of 50 and 400 microg, respectively. In patients who
      inhaled salmeterol 50microg twice daily for 10 months, a second peak
      concentration of 0.07 to 0.2 microg/L occurred 45 to 90 minutes after inhalation,
      probably because of the gastrointestinal absorption of the swallowed drug.
      Salmeterol xinafoate dissociates in solution to salmeterol and 1-hydroxy-2
      naphthoic acid. These two compounds are then absorbed, distributed, metabolised
      and excreted independently. The xinafoate moiety has no apparent pharmacological
      activity, is highly protein bound (>99%), largely to albumin, and has a long
      elimination half-life of about 12 to 15 days in healthy individuals. For this
      reason, it accumulates in plasma during repeated administration, with steady
      state concentrations reaching about 80 to 90 microg/L in patients treated with
      salmeterol 50microg twice daily for several months. The cytochrome P450 (CYP)
      isoform 3A4 is responsible for aliphatic oxidation of salmeterol base, which is
      extensively metabolised by hydroxylation with the major metabolite being alpha
      hydroxysalmeterol, with subsequent elimination predominantly in the faeces. It
      has been demonstrated that 57.4% of administered radioactivity is recovered in
      the faeces and 23% in the urine; most is recovered between 24 and 72 hours after
      administration. Unchanged salmeterol accounts for <5% of the excreted dose in the
      urine. Since the therapeutic dose of salmeterol is very low, it is unlikely that
      any clinically relevant interactions will be observed as a consequence of the
      coadministration of salmeterol and other drugs, such as fluticasone propionate,
      that are metabolised by CYP3A. All the available data clearly show that at the
      recommended doses of salmeterol, systemic concentrations are low or even
      undetectable. This is an important point, because it has been demonstrated that
      the systemic effects of salmeterol are more likely to occur with higher doses,
      which lead to approximately proportionally increased blood concentrations.

PMID- 11825097
TI  - Population pharmacokinetic model to predict steady-state exposure to once-daily
      cyclosporin microemulsion in renal transplant recipients.
AB  - BACKGROUND: The microemulsion formulation of cyclosporin (CsA-ME) has a less
      variable absorption profile than the standard formulation (CsA-S), but only
      limited information is available about once-daily administration of CsA-ME.
      OBJECTIVE: To develop a population pharmacokinetic model for once-daily CsA-ME
      that enables the prediction of individual steady-state area under the
      concentration-time curve (AUC) on the basis of blood concentration measurements
      and patient covariates. PATIENTS AND METHODS: The steady-state pharmacokinetics
      of once-daily cyclosporin were studied in 60 stable renal transplant recipients
      before and after conversion from CsA-S to CsA-ME. For each formulation, 7 blood
      samples were collected from 50 patients (group A) at sparse timepoints over 2
      weeks, and 10 blood samples were collected from 10 patients (group B) at fixed
      timepoints over 24 hours. A 2-compartment population model assuming time-lagged
      first-order oral absorption was fitted to the data from group A, using nonlinear
      mixed effects modelling (NONMEM). The data from group B were used to evaluate the
      predictive performance of the model. RESULTS: Mean [+/- SD; coefficient of
      variation (%CV)] CsA-S doses of 245mg (+/- 92) resulted in cyclosporin blood
      concentrations of 214 microg/L (+/- 70) after 12 hours and 108 microg/L (+/- 23)
      after 24 hours; the mean estimated AUC to 24 hours was 7658 microg x h/L (30%).
      With mean CsA-ME doses of 206mg (+/- 59), cyclosporin blood concentrations were
      212 microg/L (+/- 33) and 132 microg/L (25%) after 12 and 24 hours, respectively,
      and the mean estimated AUC(24) was 9357 microg x h/L (23%). A strong correlation
      between 12-hour concentrations and AUC(24) was observed for CsA-ME (r = 0.95, p <
      0.001), but not for CsA-S (r = 0.59, nonsignificant); the correlation between 24
      hour trough concentrations and AUC(24) was weaker for both formulations (r =
      0.64, p < 0.05 and r = 0.37, nonsignificant, respectively). On the basis of the
      population model derived from group A, the single best timepoint to predict
      AUC(24) from blood cyclosporin concentration was at 8 hours [AUC(24) (microg x
      h/L) = 19.6 x cyclosporin concentration at 8 hours (microg/L) + 3035], resulting
      in a prediction error of 8.3 +/- 6.6% when applied to the measured AUC(24) of
      group B. Adverse events were observed after conversion in 18 patients; these
      events generally resolved spontaneously or after dosage reduction, but twice
      daily administration was required in some patients. CONCLUSIONS: Switching from
      once-daily CsA-S to CsA-ME results in more consistent and predictable cyclosporin
      pharmacokinetics. Adjustment of dosage or regimen may be required in some
      patients.

PMID- 11825098
TI  - Maximum a posteriori Bayesian estimation of oral cyclosporin pharmacokinetics in
      patients with stable renal transplants.
AB  - OBJECTIVE: To develop a maximum a posteriori probability (MAP) Bayesian estimator
      for the pharmacokinetics of oral cyclosporin, based on only three timepoints, and
      evaluate its performance with respect to a full-profile nonlinear regression
      approach. PATIENTS: 20 adult patients with stable renal transplants given orally
      administered microemulsified cyclosporin and mycophenolate. METHODS: Cyclosporin
      was assayed by liquid chromatography-mass spectrometry. Nonlinear regression and
      MAP Bayesian estimation were performed using a home-made program and a previously
      designed pharmacokinetic model including an S-shaped absorption profile described
      by a gamma distribution. OUTCOME MEASURES AND RESULTS: MAP Bayesian estimation
      using the best limited sampling strategy (before administration, and 1 and 3
      hours after administration) was compared with nonlinear regression (taken as the
      reference method) for the prediction of the different pharmacokinetic parameters
      and exposure indices. Median relative prediction error was -0.49 and -3.42% for
      area under the concentration-time curve over the administration interval of 12
      hours (AUC12) and estimated peak drug concentration (Cmax), respectively
      (nonsignificant). Relative precision was 2.00 and 4.32%, and correlation
      coefficient (r) was 0.985 and 0.955, for AUC12 and Cmax, respectively.
      CONCLUSION: This paper reports preliminary results in a stable renal transplant
      patient population, showing that MAP Bayesian estimation can allow accurate
      prediction of AUC12 and Cmax with only three samples (0, 1 and 3 hours). Although
      these results require confirmation by further studies in other clinical settings,
      using other drug combinations, other analytical methods and commercially
      available pharmacokinetic software, the method seems promising as a tool for the
      therapeutic drug monitoring of cyclosporin in clinical practice or for exposure
      controlled studies.

PMID- 11825100
TI  - Seizures in HIV-seropositive individuals: epidemiology and treatment.
AB  - Seizures are a relatively common occurrence in patients with HIV infection. They
      may be a result of HIV infection of the CNS or a manifestation of an
      opportunistic infection. Because seizures are likely to recur in patients
      infected with HIV and because they are a poor prognostic indicator, it is
      generally recommended that all HIV-seropositive patients experiencing a first
      seizure without a recognisable and reversible cause be treated. Clinicians faced
      with treating seizures in HIV-seropositive patients often encounter a therapeutic
      dilemma since few data exist in this area. In selecting appropriate
      anticonvulsant therapy, clinicians must consider both therapy-compromising drug
      drug and drug-disease interactions. Ideal anticonvulsants for this setting are
      those that do not effect viral replication, have limited protein binding and have
      no effects on the cytochrome P450 system, such as gabapentin, topiramate and
      tiagabine. Unless the benefits outweigh the risks, valproic acid (sodium
      valproate) should be avoided as it has been shown to stimulate HIV replication.
      Since few data exist, controlled trials examining pharmacokinetic and
      pharmacodynamic interactions between anticonvulsants and antiretrovirals are
      needed. Until such time, clinicians caring for these patients should examine
      existing data carefully and employ vigilant monitoring.

PMID- 11825099
TI  - Atypical antipsychotic-induced diabetes mellitus: how strong is the evidence?
AB  - Atypical antipsychotics offer significant improvements over older, conventional
      antipsychotic agents. However, recently the newer agents have been linked to
      medical morbidity including hyperglycaemia, diabetes mellitus, bodyweight gain
      and abnormal lipid levels. Even more concerning, because of a significant risk of
      death, there have been numerous case reports of patients treated with clozapine
      or olanzapine developing diabetic ketoacidosis shortly after initiation of the
      drug. Much of the information concerning the medical morbidity of diabetes
      mellitus is based on case reports, retrospective chart reviews, naturalistic
      studies and cross-sectional studies. While definitive studies have yet to be
      reported, mounting evidence suggests that the atypical antipsychotic agents,
      particularly clozapine and olanzapine, may significantly impair glucose
      metabolism and increase the risk of diabetes in patients with schizophrenia.
      Diabetic ketoacidosis, although it appears to be uncommon, is of great concern
      secondary to the risk of death. Patients treated with atypical antipsychotic
      agents should be routinely screened for diabetes and other metabolic
      abnormalities including raised lipid levels. Patients with risk factors for
      diabetes should be monitored more closely. Reports and clinical experience
      suggest that in a case of atypical antipsychotic-associated diabetes or diabetic
      ketoacidosis, discontinuation of the antipsychotic agent may result in complete
      resolution of the hyperglycaemia and diabetes.

PMID- 11825101
TI  - Prescribing of psychotropics in the elderly: why is it so often inappropriate?
AB  - Psychotropic medications are an important treatment approach to mental health
      disorders; such disorders are common in the elderly population. Elderly patients
      are more likely to experience adverse effects from these agents than their
      younger counterparts due to age-related changes in pharmacodynamic and
      pharmacokinetic parameters. Because of these factors, inappropriate use of
      psychotropic medications in elderly patients has become a focus of concern. In
      general an agent is considered inappropriate if the risk associated with its use
      exceeds its benefit. Implicit and explicit criteria for inappropriate use of
      medications in the elderly have been created and include psychotropic agents.
      These criteria vary in their make-up but the explicit criteria tend to agree that
      amitriptyline, doxepin, and benzodiazepines that have long half-lives are not
      appropriate. Although explicit inappropriate medication criteria have been in
      existence since 1991, elderly patients continue to receive inappropriate
      psychotropic medications. A wide array of factors may be responsible for this
      practice. Provider-related causes include deficits in knowledge, confusion due to
      the lack of a consensus on the inappropriate psychotropic criteria, difficulties
      in addressing an inappropriate medication started by a previous provider,
      multiple prescribers and pharmacies involved in the care of a patient, negative
      perceptions regarding aging, and cost issues. Patients may contribute to the
      problem by demanding an inappropriate medication. Finally, the healthcare setting
      may inadvertently contribute to inappropriate prescribing by such policies as
      restrictive formularies or lack of reimbursement for pharmacists' clinical
      services. Successful approaches to optimising prescribing have been either
      educational or administrative. Educational approaches (e.g. one-on-one sessions,
      academic detailing) seek to influence decision making, while administrative
      approaches attempt to enforce policies to curtail the undesired practice. The US
      Omnibus Budget Reconciliation Act of 1987, which improved psychotropic medication
      use in long-term care, is an excellent example of administrative intervention.
      More research specifically focused on the causes of inappropriate psychotropic
      medication use and methods to avoid this practice is needed before targeted
      recommendations can be made.

PMID- 11825102
TI  - Depression and heart disease: evidence of a link, and its therapeutic
      implications.
AB  - Over several decades, a large body of evidence has emerged to suggest that
      depressive disorder is a risk factor for heart diseases, both aetiologically and
      prognostically. Several large, prospective, longitudinal studies have examined
      the relationship between depression and the development of coronary artery
      disease (CAD); they reveal that the relationship is significant and independent
      of conventional risk factors. Prognostic studies have shown that depression is
      associated with two to three times higher mortality after myocardial infarction,
      unstable angina or coronary artery bypass grafting, and in patients with stable
      CAD compared with such patients without depression. Depression also has been
      found to increase mortality and morbidity in patients with heart failure,
      regardless of its aetiology. Such adverse associations persist after adjustment
      for conventional prognostic risk factors. Despite all of these findings,
      depressed patients with heart disease are less likely to be recognised clinically
      as being depressed than those patients who have depression but no heart disease.
      The very limited evidence available from pharmacological clinical trials raises
      concern about the safety of antidepressants in CAD and heart failure. In
      addition, no research has addressed whether the treatment of depression in
      patients with heart disease will improve their prognosis.

PMID- 11825104
TI  - Spotlight on fluvoxamine in anxiety disorders in children and adolescents.
AB  - Fluvoxamine is a selective serotonin reuptake inhibitor (SSRI) which may be used
      for the management of anxiety disorders in children and adolescents. Absorption
      of fluvoxamine was similar in adolescents to that in adults, which suggests that
      the maximum dosage of the drug for patients aged between 12 and 17 years can be
      as high as 300 mg/day. However, steady-state plasma fluvoxamine concentrations
      were 2 to 3 times higher in children (aged between 6 and 11 years) than in
      adolescents; thus, the maximum fluvoxamine dosage recommended for children is 200
      mg/day. Fluvoxamine (50 to 300 mg/day) for 8 to 16 weeks significantly reduced
      symptoms of obsessive-compulsive disorder (OCD) [measured across multiple
      assessment scales] compared with placebo in a well controlled trial in paediatric
      patients (n = 120) or from baseline in noncomparative trials in adolescent (n =
      20) or paediatric (n = 16) patients. Improvements with fluvoxamine (up to 200
      mg/day) were observed for up to 1 year in 98 patients with OCD in a
      noncomparative trial. The drug (up to 250 or 300 mg/day) also improved symptoms
      of anxiety compared with placebo in an 8-week well controlled trial in 128
      paediatric patients with social phobia, separation anxiety disorder or
      generalised anxiety disorder (GAD). Fluvoxamine (50 to 300 mg/day) appears to be
      well tolerated in paediatric patients, with most adverse events with the drug
      (except abdominal discomfort, which occurred more often in patients receiving
      fluvoxamine) occurring with a similar incidence to those with placebo. The most
      common adverse events involved the CNS or gastrointestinal system. Most adverse
      events reported by paediatric patients with OCD were similar to those reported by
      adults. In conclusion, fluvoxamine is generally well tolerated and has
      demonstrated short-term efficacy compared with placebo in the treatment of OCD,
      and social phobia, separation anxiety disorder or GAD in well controlled trials
      in paediatric patients. Reductions in symptoms of anxiety with fluvoxamine have
      been observed for up to 1 year in children and adolescents with OCD. However,
      there are currently no comparative trials of fluvoxamine with other
      pharmacological agents. In the absence of such trials, current consensus opinion
      recommends that when pharmacotherapy is indicated, fluvoxamine, like other SSRIs,
      can be used as first-line treatment for anxiety disorders, particularly OCD, in
      paediatric patients. However, direct comparisons are required to assess the
      relative efficacy and tolerability of pharmacological agents in order to make
      firm recommendations for the treatment of anxiety disorders in this patient
      group.

PMID- 11825105
TI  - Metastatic carcinomatous cirrhosis and hepatic hemosiderosis.

PMID- 11825103
TI  - Is attention deficit hyperactivity disorder increasing among girls in the US?
      Trends in diagnosis and the prescribing of stimulants.
AB  - OBJECTIVE: To use a single national data source to discern trends in the
      prevalence of office-based visits resulting in a diagnosis of attention deficit
      hyperactivity disorder (ADHD) among girls, and trends in the prescribing of
      stimulant pharmacotherapy (including methylphenidate) for its treatment in the
      US. METHODS: Data from the US National Ambulatory Medical Care Survey were
      utilised for this analysis. The number and rate of office-based physician visits
      resulting in a diagnosis of ADHD (International Classification of Diseases, 9th
      Revision, Clinical Modification code 314.00 or 314.01) were discerned from the
      beginning of 1990 to the end of 1998, for children aged 5 to 18 years. Gender
      specific trend analyses were conducted using four time intervals: 1991 to 1992,
      1993 to 1994, 1995 to 1996, and 1997 to 1998. RESULTS: The estimated number of
      office-based visits documenting a diagnosis of ADHD among children increased from
      947 208 in 1990 to 3 234 180 in 1998. The rate of office-based visits documenting
      a diagnosis of ADHD among children increased from 19.4 per 1000 of the US
      population aged 5 to 18 years in 1990 to 59.0 per 1000 in 1998, a 3-fold increase
      (p < 0.05). The annualised mean number of office-based visits documenting a
      diagnosis of ADHD among girls tripled between 1991 to 1992 and 1997 to 1998 (from
      296 389 to 886 798), whereas the number for boys increased 2.2-fold (from 1 006
      243 to 2 200 021). The US population-adjusted rate of office-based visits
      documenting a diagnosis of ADHD among girls increased 2.7-fold between 1991 to
      1992 and 1997 to 1998 (from 12.3 per 1000 girls to 33.4 per 1000; p < 0.05),
      whereas the rate among boys doubled (from 39.5 per 1000 boys to 78.7 per 1000; p
      < 0.05). Documentation of a diagnosis of ADHD and the prescribing of stimulant
      pharmacotherapy increased 2.8-fold for girls, from 7.5 per 1000 girls in 1991 to
      1992 to 21.1 per 1000 in 1997 to 1998 (p < 0.05), as compared with a 2.2-fold
      increase among boys (from 25.5 per 1000 boys to 57.0 per 1000; p < 0.05).
      CONCLUSION: Over the time frame 1990 to 1998, the rate of ADHD as well as the
      prescribing of stimulant medications for its treatment increased significantly
      among children aged 5 to 18 years. Between 1991 to 1992 and 1997 to 1998, the
      increased rate of diagnosis of ADHD among girls contributed to the overall upward
      trend. The rapidly increasing rate of ADHD among girls, and the prolonged nature
      of the disorder, represent significant public health problems. There exists a
      need for additional research examining both the aetiology and treatment of ADHD
      by gender.

PMID- 11825107
TI  - The laboratory diagnosis of platelet disorders.
AB  - OBJECTIVE: To provide both a detailed description of the laboratory tests
      available in the diagnosis of platelet disorders and a testing algorithm, based
      on platelet count, that can be used to direct the evaluation of platelet
      disorders. DATA SOURCES: A literature search was conducted using the National
      Library of Medicine database. STUDY SELECTION: The literature on laboratory
      testing of platelet function was reviewed. DATA EXTRACTION AND DATA SYNTHESIS:
      Based on the literature review, an algorithm for platelet testing was developed.
      CONCLUSIONS: A history of mucocutaneous bleeding often indicates abnormal
      platelet function that can be associated with a normal, increased, or decreased
      platelet count. Multiple laboratory procedures can now be used to determine the
      underlying pathologic condition of platelet dysfunction when other deficiencies
      or defects of the coagulation cascade or fibrinolysis are ruled out. Simple
      procedures, such as platelet count, peripheral blood smear, and a platelet
      function screening test, will often lead the investigator to more specific
      analyses. Although platelet function testing is often limited to larger medical
      centers with highly trained technologists, newer technologies are being developed
      to simplify current procedures and make platelet function testing more
      accessible. This review provides an algorithm for platelet testing that may be of
      benefit to pathologists and physicians who deal with hemostatic disorders.

PMID- 11825108
TI  - Do proficiency testing participants learn from their mistakes? Experience from
      the EXCEL throat culture module.
AB  - CONTEXT: Participation in proficiency testing is required under the Clinical
      Laboratory Improvement Amendments of 1988. Although the primary purpose of this
      testing is evaluation of current laboratory performance, a major secondary
      benefit of such testing is postulated to be progressive improvement in laboratory
      performance over time as laboratories learn from their previous experiences and
      feedback. OBJECTIVE: To test the hypothesis that a secondary result of
      proficiency testing is improvement over time of laboratory performance. DESIGN:
      The performance of participants in a large proficiency testing program (EXCEL),
      designed for clinic and office laboratories, on a specific problematic
      competence, the ability to differentiate group A streptococcus from group C
      streptococci, was monitored during a 6-year period (1996-2001) for changes in
      participant performance. INTERVENTIONS: With each testing cycle, feedback on
      performance relative to peers and an educational discussion analyzing performance
      and suggesting best practices was submitted to participants. RESULTS: Despite
      consistent feedback, there was no significant change in participant performance
      throughout the period studied. CONCLUSIONS: In a large, stable proficiency
      testing program, a significant throat culture competence, which demonstrated less
      than optimal performance, did not improve over time, suggesting that current
      utilization of proficiency testing results in laboratory improvement programs is
      suboptimal.

PMID- 11825109
TI  - Quality indicators of blood utilization: three College of American Pathologists Q
      Probes studies of 12,288,404 red blood cell units in 1639 hospitals.
AB  - OBJECTIVES: To determine the normative rates of blood unit crossmatched to
      transfused (C:T) ratios, red blood cell (RBC) unit wastage, and RBC unit
      expiration that exist in hospital communities throughout the United States, and
      to examine hospital blood bank practices associated with more desirable (lower)
      rates. DESIGN: In 3 separate studies, participants in the College of American
      Pathologists Q-Probes laboratory quality improvement program collected data
      retrospectively on the number of transfusion crossmatches performed in their
      institutions and the number of RBC-containing units that were transfused into
      patients, the number of units that expired (outdated) prior to being utilized,
      and the number that were wasted due to mishandling. Participants also completed
      questionnaires describing their hospitals' and blood banks' laboratory and
      transfusion practices. SETTING AND PARTICIPANTS: One thousand six hundred thirty
      nine public and private institutions, well more than 80% of which were known to
      be located in the United States. MAIN OUTCOME MEASURES: Quality indicators of
      blood utilization (namely, the C:T ratio, the rate of RBC unit expiration, and
      the rate of RBC unit wastage). RESULTS: Participants submitted data on 12,288,404
      RBC unit transfusions. The C:T ratios were 1.5 or less in the top-performing 10%
      of participating institutions (90th percentile and above), 1.8 to 1.9 in the
      midrange of participating institutions (50th percentile), and 2.4 or greater in
      the bottom-performing 10% of participating institutions (10th percentile and
      below). Red blood cell unit expiration rates were 0.1% or less at the 90th
      percentile and above, 0.3% to 0.9% at the 50th percentile, and 3.5% or greater at
      the 10th percentile and below. Red blood cell unit wastage rates were 0.1% or
      less at the 90th percentile and above, 0.1% to 0.4% at the 50th percentile, and
      0.7% or greater at the 10th percentile and below. Depending on which quality
      indicator was examined, lower values (ie, better performances) were found in
      institutions that had fewer than 200 hospital beds, no teaching programs, no on
      site full-time medical directors of transfusion services, did not utilize maximum
      surgical blood order schedules, set C:T threshold goals of 2.0 or less, monitored
      categories of health care workers responsible for RBC wastage, monitored requests
      for RBC components by transfusion indication, did not accept short-dated units
      from blood distribution centers, and if they did accept short-dated units, were
      allowed to return those units to the distribution centers. CONCLUSIONS: Hospital
      blood bank personnel can achieve C:T ratios below 2.0, RBC unit expiration rates
      below 1.0%, and RBC unit wastage rates below 0.5%. Lower C:T ratios and/or RBC
      unit expiration rates were associated with blood bank personnel setting C:T
      thresholds of 2.0 or less, monitoring requests for blood components by
      transfusion indication criteria, monitoring categories of health care workers
      responsible for blood wastage, not accepting short-dated units from blood
      distribution centers, and if short-dated units were accepted, being allowed to
      return those units to the blood distribution center. These practices were not
      associated with lower blood wastage rates.

PMID- 11825110
TI  - Livebirths with placental hemorrhagic endovasculitis: interlesional relationships
      and perinatal outcomes.
AB  - BACKGROUND AND OBJECTIVE: Hemorrhagic endovasculitis (HEV) is a vasodisruptive
      alteration of fetal-placental blood vessels that has been associated with
      perinatal morbidity and mortality and abnormalities of growth and development.
      Clinicopathologic conditions that are often identified in pregnancies with HEV
      affected placentas include villitis of unknown etiology, chorionic vessel
      thrombi, villous erythroblastosis, meconium staining, and maternal hypertension.
      The clinical implications of HEV are often disputed. This case-control study
      assesses the clinical relevance of HEV in placentas of viable infants and
      examines the interplay of coexistent intraplacental lesions. METHODS: We reviewed
      clinical records and slides from 104 livebirths with placentas affected by HEV
      above a specified severity level (cases) and 104 matched livebirths with
      placentas that were not affected by HEV (controls). We evaluated incidences of
      perinatal complications with increasing HEV severity indices in placentas with
      and without coexistent lesions. Interlesional relationships were established by
      matching HEV severity indices with severity indices of coexistent lesions.
      Hemorrhagic endovasculitis was subcategorized into active, bland, and healed
      forms and clustered capillary lesions (hemorrhagic villitis). RESULTS: Lesions
      that were frequently coexistent in HEV-affected placentas included villitis of
      unknown etiology, chorionic thrombi, villous fibrosis, erythroblastosis, and
      primary infarcts. Compared with the control group, the case group had higher
      incidences of abnormal fetal heart rate tracings (P <.003), fetal distress (P
      <.001), and growth restriction (P <.001). Increasing severities of HEV and
      coexistent lesions were associated with higher rates of perinatal complications.
      Complication rates were higher in HEV cases, with or without coexistent lesions.
      The complication rate was higher in cases affected by HEV and hemorrhagic
      villitis than in cases affected by HEV alone (P <.03). Significant interlesional
      relationships were evident between HEV and villitis of unknown etiology,
      chorionic thrombi, villous fibrosis, and erythroblastosis. CONCLUSIONS; Severe
      forms of HEV can occur in placentas of livebirths. The severity of HEV and
      associated lesions and the presence of hemorrhagic villitis have important
      clinical implications. Interlesional relationships between HEV and thrombotic,
      chronic inflammatory, and chronic vaso-occlusive lesions exist. Pregnancies with
      HEV-affected placentas with or without coexistent lesions are at risk for
      perinatal complications.

PMID- 11825111
TI  - Identification of numerical chromosomal changes detected by interphase
      fluorescence in situ hybridization in high-grade prostate intraepithelial
      neoplasia as a predictor of carcinoma.
AB  - CONTEXT: High-grade prostate intraepithelial neoplasia (HPIN) is the most likely
      precursor of prostate cancer. The condition of many patients with a diagnosis of
      HPIN in prostate needle core biopsy could, if left untreated, progress to
      invasive cancer. Currently there is no available clinical, immunohistochemical,
      or morphologic criteria that are predictive of this progression. OBJECTIVE: To
      determine whether chromosomal instability in these precursor lesions could
      increase their predictive value for cancer detection. DESIGN: Dual-color
      interphase fluorescence in situ hybridization analysis was performed on archived
      prostate needle core biopsies from 54 patients with initial diagnosis of isolated
      HPIN and follow-up of 3 years or more. We used commercially available centromere
      probes for chromosomes 4, 7, 8, and 10. We had interpretable results in 44
      patients as follows: (1) group A: 24 HPIN patients with persistent HPIN and/or
      benign lesions in the follow-up biopsies, and (2) group B: 20 HPIN patients with
      progression to prostate carcinoma. RESULTS: Twenty-five percent of the patients
      in group B displayed numeric chromosomal aberrations. Only 8.3% of the patients
      from group A had chromosomal abnormalities (P =.1). The observed overall
      chromosomal changes in HPIN were higher than those in normal or hyperplastic
      epithelium, with a statistically significant difference (P <.05). All aberrations
      were detected in the form of chromosomal gain. Overall, the commonest aberration
      was gain of chromosome 8, followed by gains of chromosomes 7 and 10. CONCLUSION:
      These results indicated that although no single numeric chromosomal abnormality
      could be assigned as a predictor of HPIN progression to carcinoma, the overall
      level of numeric chromosomal abnormalities shows a trend of elevation in HPIN
      patients whose condition subsequently progressed to carcinoma.

PMID- 11825112
TI  - A103 immunostaining in the diagnosis of adrenal cortical tumors: an
      immunohistochemical study of 316 cases.
AB  - CONTEXT: The monoclonal antibody A103 recognizes an antigen on melanoma cells
      known as Melan-A or MART-1. Recent studies have shown that A103 also reacts with
      adrenal cortical cells and may be useful in the diagnosis of adrenal cortical
      tumors. However, only small numbers of some of the tumors in the differential
      diagnosis of adrenal cortical neoplasms have been studied. OBJECTIVE: To study
      the specificity of A103 immunohistochemistry in a large number of tumors in the
      differential diagnosis of adrenal cortical neoplasms. DESIGN: Formalin-fixed,
      paraffin-embedded tissue from 21 adrenal cortical tumors, 16 cases of metastatic
      carcinoma to the adrenal, 10 pheochromocytomas, and 269 extra-adrenal carcinomas
      was evaluated for A103 immunoreactivity using a commercially available antibody
      (Novocastra, Newcastle, UK). RESULTS: Positive staining was seen in all of the
      adrenal cortical tumors but in none of the adrenal metastases or
      pheochromocytomas. In the 269 extra-adrenal carcinomas, A103 immunoreactivity was
      limited to a single ovarian serous carcinoma. CONCLUSION: A103 immunostaining is
      useful in distinguishing adrenal cortical neoplasms from other carcinomas and
      pheochromocytoma.

PMID- 11825096
TI  - Drug interactions with patient-controlled analgesia.
AB  - Patient-controlled analgesia (PCA) has become standard procedure in the clinical
      treatment of pain. Its widespread use in patients with all kinds of diseases
      opens a variety of possible interactions between analgesics used for PCA and
      other drugs that might be administered concomitantly to the patient. Many of
      these drug interactions are of little clinical importance. However, some drug
      interactions have been reported to result in serious clinical problems. Drug
      interactions can either predominantly affect the pharmacokinetics or
      pharmacodynamics of the drug. Most important pharmacokinetic drug interactions
      occur at the level of drug metabolism or protein binding. Acceleration of
      methadone metabolism caused by cytochrome P450 (CYP) 3A4 induction by
      antiretroviral drugs or rifampicin (rifampin) has caused methadone withdrawal
      symptoms. Lack of morphine formation from codeine as a result of CYP2D6
      inhibition by quinidine results in an almost complete loss of the analgesic
      effects of codeine. Alterations of methadone protein binding caused by an
      inhibition of alpha1-acid glycoprotein synthesis by alkylating substances are
      another possibility for predominantly pharmacokinetically based drug interactions
      during PCA. Furthermore, inhibition of P-glycoprotein by anticancer drugs could
      result in altered transmembrane transport of morphine, methadone or fentanyl,
      although this has not been shown to be of clinical relevance. Synergistic effects
      of systemically administered opioids with spinally or topically delivered opioids
      or anaesthetics have been reported frequently. The same is true for the opioid
      sparing effects of coadministered non-opioid analgesics. Antidepressants,
      anticonvulsants or alpha2-adrenoreceptor agonists have also been shown to exert
      additive analgesic effects when administered together with an opioid.
      Inconsistent findings, however, are reported regarding the treatment of patients
      with opioid-induced nausea and sedation, since coadministration of antiemetics
      either increased or decreased the respective adverse effects or revealed
      additional unwanted drug effects.

PMID- 11825113
TI  - The use of TaqMan PCR assay for detection of Bordetella pertussis infection from
      clinical specimens.
AB  - OBJECTIVE: The routine clinical laboratory detection of Bordetella pertussis is
      through culture, which can require 5 to 7 days for the bacteria to grow. Using a
      polymerase chain reaction (PCR) assay can shorten this detection time while
      increasing the sensitivity of detection with similar specificity. This study
      compared culture with TaqMan PCR for detection of B pertussis in clinical
      specimens and the turnaround time for each assay during the pertussis season.
      MATERIALS AND METHODS: Nasopharyngeal swabs in Regan-Lowe transport media were
      collected from 1556 persons who had symptoms of whooping cough or who had had
      contact with infected persons; the swabs were submitted for B pertussis detection
      during the pertussis season. A single nasopharyngeal swab from each patient was
      submitted for both culture and TaqMan PCR detection. Upon receipt of the
      specimens, the swabs were inoculated onto Regan-Lowe agar for culture and
      incubated for up to 7 days. The same swab was processed for PCR detection using
      TaqMan PCR assay. A second nested PCR was used on positive specimens for
      resolution purposes. The TaqMan PCR assay was performed 3 to 5 days a week,
      whereas the culture was performed 6 days a week. All specimens were processed on
      the same day or earliest possible working day for TaqMan or culture, and
      specimens queued for resolution by nested PCR were batched. RESULTS: There were a
      total of 275 PCR positives and 28 culture positives. After resolution with the
      second nested PCR, the sensitivity, specificity, positive predictive value, and
      negative predictive value were 100%, 97.4%, 87.6%, and 100% for TaqMan PCR and
      11.6%, 100%, 100%, and 85.7% for culture. The average turnaround time for
      positive culture was 5.1 days, and the average turnaround time for PCR was 2.3
      days. CONCLUSION: The TaqMan PCR assay has superior sensitivity and shorter
      turnaround time over culture because it can be finished within one working day.
      Furthermore, the same swab can be used for culture of the bacteria for antibiotic
      susceptibility testing. The early detection of pertussis using TaqMan PCR assay
      allows early intervention on the spread of the disease and the ability to culture
      the bacteria from the same swab, thereby eliminating the need for a second swab
      and allowing for detection of antibiotic resistance.

PMID- 11825114
TI  - Radioimmunohistochemistry of epidermal growth factor receptor in breast cancer.
AB  - CONTEXT: Conflicting reports of epidermal growth factor receptor (EGFR)
      expression in breast cancer and inconstant relationships with established
      prognostic indicators and outcomes suggest difficulties with EGFR measurement.
      OBJECTIVE: To compare EGFR measurement in a panel of cell lines and in breast
      carcinomas by radioimmunohistochemistry (R-IHC), conventional
      immunohistochemistry (IHC), and a ligand binding (LB) assay. DESIGN: Eight EGFR
      expressing cell lines and 50 primary breast carcinoma specimens were analyzed for
      EGFR by IHC, R-IHC, and LB assays. A further 153 primary breast cancer specimens
      were analyzed by R-IHC alone. RESULTS: All 3 assays were in good agreement for
      the cell lines. In the subset of the 50 carcinoma specimens, EGFR was detected by
      LB assays in 19 (38%) and by IHC in 24 (48%). However, R-IHC detected EGFR in 46
      (92%) of 50 and in 186 (92%) of all 203 carcinoma specimens. The LB assay agreed
      poorly with R-IHC of carcinomas, possibly because the LB assay is sensitive to
      EGFR-expressing nontumor breast parenchyma in the tissue analyzed. Both IHC and R
      IHC on carcinoma specimens agreed better, but 26 carcinoma specimens (52%) in
      which EGFR was not detectable by IHC had a 10-fold range in receptor level
      detectable by R-IHC. CONCLUSION: To elucidate the role of EGFR or other growth
      factor receptors in breast cancer requires accurate, sensitive receptor assays.
      With its dynamic range, R-IHC returned meaningful results over the entire range
      of expression actually present in breast cancer, which LB assays and IHC failed
      to do.

PMID- 11825115
TI  - Autopsy findings in a human immunodeficiency virus-infected population over 2
      decades: influences of gender, ethnicity, risk factors, and time.
AB  - OBJECTIVES: To examine autopsy pathology in an urban population infected with the
      human immunodeficiency virus (HIV) and to determine if age at death and disease
      frequencies are associated with gender, HIV risk factors, ethnicity, and
      therapeutic era. DESIGN AND METHODS: Retrospective analysis of autopsy data from
      394 HIV-infected adults. The population was divided into 3 therapeutic eras for
      analysis: group A, 1979-1986; group B, 1987-1995; and group C, 1996-2000.
      RESULTS: Women died at significantly younger ages than men (mean +/- SEM age,
      38.9 +/- 1.0 years vs 42.5 +/- 0.64 years), even after adjustment for risk
      factors, ethnicity, and therapeutic era. This age discrepancy occurred despite a
      lower prevalence of arteriosclerosis, cachexia, and hepatitis B in women and no
      significant differences in the frequencies of other infectious diseases. Whites
      had a longer survival than patients of other ethnicities (mean age at death, 44.7
      +/- 1.2 years for whites, 39.9 +/- 0.80 years for blacks, and 41.3 +/- 0.87 years
      for Hispanic individuals). Renal, cardiac, and splenic pathologies, Mycobacterium
      avium-intracellulare (MAI) infection, and cachexia were more common in blacks
      than in whites and/or Hispanic individuals, and cytomegalovirus and systemic
      lymphoma were more common in whites and Hispanic individuals than in blacks.
      Diseases associated with intravenous drug use were hepatitis C, cirrhosis, and
      tuberculosis; those with all sexual risk factors, cytomegalovirus infection,
      herpes simplex virus infection, and Pneumocystis carinii pneumonia; and those
      with homosexual risk, Kaposi sarcoma and MAI infection. The prevalence of many
      disease entities changed over time: compared with the other groups, group C had
      lower prevalences of many viral and fungal illnesses, MAI infection, systemic
      lymphoma, cachexia, and Kaposi sarcoma and higher prevalences of hepatitis,
      cirrhosis, arteriosclerosis, staphylococcal and streptococcal infections, and
      traumatic lesions. When the data were adjusted for changing demographic and risk
      composition, the only significant changes in disease frequency for period C were
      decreased prevalences of PCP and Kaposi sarcoma and increased prevalences of
      cirrhosis and arteriosclerosis. CONCLUSIONS: Significant gender- and ethnicity
      related differences in age of death occurred in this HIV-infected population, and
      these differences were not explained by the frequencies of diseases. The lower
      prevalences of PCP and Kaposi sarcoma in group C are likely a reflection of the
      impact of potent therapies on causes of mortality. The higher prevalences of
      cirrhosis and arteriosclerosis suggest that entities not targeted by
      antiretroviral reconstitution of immunity will play an increasingly important
      role in HIV-related mortality in the future.

PMID- 11825116
TI  - A Kaposi-like variant of splenic angiosarcoma lacking association with human
      herpesvirus 8.
AB  - We report the case of a Kaposi-like variant of splenic angiosarcoma in a 28-year
      old woman. The tumor featured a Kaposi sarcoma-like spindle cell proliferation
      with slit formation and markedly dilated spongelike vascular channels filled with
      erythrocytes. Thirteen months following the initial splenectomy, metastatic
      lesions were found in the patient's liver and bone marrow. The proliferating
      cells were positive for factor VIII-associated antigen and CD34. The human
      herpesvirus 8 genome, which is regarded as a diagnostic feature of Kaposi
      sarcoma, was not detected by polymerase chain reaction analysis. Although the
      histologic findings were similar, this Kaposi-like variant of splenic
      angiosarcoma must be considered distinct from Kaposi sarcoma.

PMID- 11825117
TI  - Fine-needle aspiration biopsy diagnosis of "invasive" temporomandibular joint
      pigmented villonodular synovitis.
AB  - The clinical and aspiration cytologic details of a case of temporomandibular
      joint pigmented villonodular synovitis are presented and correlated with imaging,
      surgical, histopathologic, and clinical follow-up findings; the origin of such
      lesions is discussed. The lesion originally presented in a 36-year-old, otherwise
      healthy, white man as a unilateral mass involving the temporal fossa and
      temporomandibular joint region. The tumor's extent was defined by magnetic
      resonance imaging and computed tomographic scan; there was destruction of the
      temporomandibular joint and erosion of the temporal cranial bones by a lesion
      whose maximum dimensions were estimated by imaging to be 2.75 x 3.25 cm. The
      lesion was initially sampled and classified by computed tomography-guided fine
      needle aspiration biopsy. Following complete resection, the original diagnosis
      was confirmed with both hematoxylin-eosin-stained paraffin sections and
      immunohistochemical staining. The patient remains free of disease 7 years
      postoperatively.

PMID- 11825118
TI  - Dutcher bodies in chronic synovitis.
AB  - Dutcher bodies are periodic acid-Schiff-positive intranuclear pseudoinclusions
      found in plasma cells in mucosa-associated lymphoid tissue lymphoma, Waldenstrom
      macroglobulinemia, and myeloma. We describe the case of a 68-year-old woman with
      chronic synovitis containing multiple Dutcher bodies. The patient's workup for
      lymphoma was negative. Hematoxylin-eosin- and periodic acid-Schiff-stained
      sections of 7 cases of marked chronic synovitis selected from the files spanning
      a 10-year period at Memorial Hospital of Rhode Island (Pawtucket, RI) were
      examined, and none showed Dutcher bodies. This case illustrates that Dutcher
      bodies may rarely occur in benign reactive conditions, such as chronic synovitis.

PMID- 11825119
TI  - Detection of microsatellite instability from archival, hematoxylin-eosin-stained
      colorectal cancer specimen.
AB  - Microsatellite instability (MSI) is characteristic of hereditary nonpolyposis
      colorectal cancer (HNPCC). Owing to early onset of colorectal cancer before the
      age of 50 years and/or familial clustering of HNPCC-related malignancies, the
      diagnosis of HNPCC was suspected in 2 patients. Because no paraffin-embedded
      tumor tissue was available, we used archival 5-microm, hematoxylin-eosin-stained
      tumor specimen slides for direct MSI analysis. Tissue was microdissected and
      cells were lysed using 1% Triton. Fluorescence polymerase chain reaction
      amplification of a panel of 7 microsatellite markers, including all markers of
      the current international reference panel (BAT-25, BAT-26, D2S123, D5S346, and
      D17S250), demonstrated MSI in one patient and excluded MSI in the other. In
      conclusion, this study demonstrates the feasibility of MSI analysis by direct
      fluorescence polymerase chain reaction amplification using hematoxylin-eosin
      stained tissue specimens without the need for prior DNA extraction.

PMID- 11825120
TI  - Necrotic seminoma of the testis: establishing the diagnosis with Masson trichrome
      stain and immunostains.
AB  - We describe an infarcted mass in the testis containing "ghost" cells suspicious
      for neoplasm. The entire lesion was necrotic. A Masson trichrome stain greatly
      improved nuclear and cytologic detail, confirming the suspicion of neoplasm.
      Placental alkaline phosphatase revealed specific membrane staining of the
      neoplastic cells and established a diagnosis of seminoma. Masson trichrome plus
      selected immunostains offer a promising approach to the diagnosis of certain
      necrotic neoplasms.

PMID- 11825121
TI  - Pseudallescheriasis as an aggressive opportunistic infection in a bone marrow
      transplant recipient.
AB  - Pseudallescheria boydii is a low-virulence fungus that is the main causative
      agent of posttraumatic mycetoma in a nonimmunocompromised host. Immunocompromised
      patients are at high risk for locally invasive or disseminated Pseudallescheria
      infection. However, aggressive opportunistic infections due to P boydii are
      reported infrequently because it morphologically resembles other fungi,
      especially Aspergillus species, on tissue histology; therefore, such infections
      are not identified and treated properly. We report a case of disseminated P
      boydii infection in a patient following bone marrow transplantation. The identity
      of the fungus was not recognized until microbiologic culture results became
      available. Our case illustrates the importance of recognizing this fungus as an
      opportunistic infection in immunocompromised patients, as well as the need for
      culture of biopsy material for proper identification so that appropriate therapy
      can be instituted.

PMID- 11825122
TI  - Cotyledonoid leiomyoma: a benign uterine tumor with alarming gross appearance.
AB  - Cotyledonoid leiomyoma or "grapelike" leiomyoma is a very rare tumor among the
      ever-expanding repertoire of growth variants described in benign uterine
      leiomyoma. We report a case of cotyledonoid leiomyoma in a 55-year-old woman who
      presented with menorrhagia and uterine prolapse. A large multinodular fungating
      tumor adhering to the right posterolateral wall of the uterus and extending to
      the broad ligament was discovered at vaginal hysterectomy. With a provisional
      diagnosis of sarcoma, total hysterectomy and bilateral salpingo-oophorectomy were
      performed. Postoperatively, the patient was well with no evidence of recurrence
      at 14 months. Pathologic examination revealed a 10-cm, red-brown tumor that
      comprised multiple bulbous processes protruding over the uterine surface, in
      continuity with a dissecting intramyometrial component. It was composed of
      fascicles and nodules of bland-looking smooth muscle cells with prominent
      perinodular hydropic degeneration. Coagulative necrosis, mitoses, and nuclear
      atypia were absent. Cotyledonoid leiomyoma apparently results from a combination
      of several uncommon growth patterns operating together, including subserosal
      growth, dissecting growth, and perinodular hydropic degeneration. Increased
      awareness of this grossly alarming variant of benign uterine leiomyoma can help
      avoid overtreatment.

PMID- 11825123
TI  - Splenic marginal zone lymphoma: a case report and review of the literature.
AB  - Splenic marginal zone lymphoma is a recently described primary splenic
      lymphoproliferative disorder that mainly affects older individuals. We report the
      case of a 22-year-old woman with morphologic and immunophenotypic findings
      consistent with splenic marginal zone lymphoma. This woman is one of the youngest
      patients ever described with this disease. The patient presented with complaints
      of left-sided abdominal fullness and was noted to have splenomegaly on physical
      examination. Laboratory evaluation revealed pancytopenia and a serum M component.
      The spleen was removed and weighed 1550 g. Histology showed prominent white pulp
      with an expanded marginal zone. The neoplastic cells were marginal zone-type
      cells with small to intermediate-sized nuclei with occasional conspicuous
      nucleoli and moderate amounts of pale to amphophilic cytoplasm. Immunophenotypic
      analysis revealed a B-cell population (CD20 positive) with kappa-light-chain
      restriction. The patient was treated with adjuvant therapy, but developed
      progressive disease less than 2 years after initial diagnosis.

PMID- 11825124
TI  - Cholesterol granuloma of the maxillary sinus.
AB  - Cholesterol granuloma is usually associated with chronic middle ear disease and
      is common in the mastoid antrum and air cells of the temporal bone. It has also
      been reported in other parts of the skull, such as the frontal and maxillary
      sinuses and orbit. Cholesterol granuloma is rare in the paranasal sinuses. We
      report a new case of cholesterol granuloma in the maxillary sinus of a 38-year
      old man who underwent surgical excision. We also review the literature and
      discuss the mechanism of development for this lesion. The resected specimen
      showed fragments of respiratory mucosa with cholesterol clefts surrounded by
      multinucleated foreign-body giant cells. Some multinucleated foreign-body giant
      cells showed asteroid bodies. Hemorrhagic areas, hemosiderin-laden macrophages,
      chronic inflammatory cells, and dilated lymphatics vessels were seen as well.
      Increased intrasinus pressure due to drainage obstruction may affect venous and
      lymphatic drainage from the sinus cavity, leading to venule microhemorrhages
      while still allowing arterial blood into the sinus mucosa and further
      contributing to a large localized hemorrhage. Lymphatic drainage may be
      insufficient to completely remove the lipid components of the red blood cells,
      and the lipid accumulation may contribute to the formation of cholesterol
      crystals and their esters.

PMID- 11825125
TI  - Universal leukocyte reduction: state of the art and the nature of decision
      making.

PMID- 11825126
TI  - Pathologic quiz case: a 41-year-old woman with bilateral nodular breasts.

PMID- 11825127
TI  - Pathologic quiz case: incidental hepatic nodule on abdominal laparotomy.

PMID- 11825128
TI  - Pathologic quiz case: adolescent girl presenting with solitary pulmonary nodule.

PMID- 11825129
TI  - Pathologic quiz case: a cystic pancreatic mass discovered in a patient with
      ileocecal carcinoid.

PMID- 11825130
TI  - Small intestinal intussusception secondary to a submucosal lipoma.

PMID- 11825131
TI  - Revised prevalence estimates of mental disorders in the United States: using a
      clinical significance criterion to reconcile 2 surveys' estimates.
AB  - BACKGROUND: Current US mental disorder prevalence estimates have limited
      usefulness for service planning and are often discrepant. Data on clinical
      significance from the National Institute of Mental Health Epidemiologic Catchment
      Area Program (ECA) and the National Comorbidity Survey (NCS) were used to produce
      revised estimates, for more accurate projections of treatment need and further
      explication of rate discrepancies. METHODS: To ascertain the prevalence of
      clinically significant mental disorders in each survey, responses to questions on
      life interference from, telling a professional about, or using medication for
      symptoms were applied to cases meeting symptom criteria in the ECA (n = 20,861)
      and NCS (n = 8098). A revised national prevalence estimate was made by selecting
      the lower estimate of the 2 surveys for each diagnostic category, accounting for
      comorbidity, and combining categories. RESULTS: Using data on clinical
      significance lowered the past-year prevalence rates of "any disorder" among 18-
      to 54-year-olds by 17% in the ECA and 32% in the NCS. For adults older than 18
      years, the revised estimate for any disorder was 18.5%. Using the clinical
      significance criterion reduced disparities between estimates in the 2 surveys.
      Validity of the criterion was supported by associations with disabilities and
      suicidal behavior. CONCLUSIONS: Establishing the clinical significance of
      disorders in the community is crucial for estimating treatment need. More work
      should be done in defining and operationalizing clinical significance, and
      characterizing the utility of clinically significant symptoms in determining
      treatment need even when some criteria of the disorder are not met. Discrepancies
      in ECA and NCS results are largely due to methodologic differences.

PMID- 11825132
TI  - Lowered estimates--but of what?

PMID- 11825133
TI  - Mortality associated with sleep duration and insomnia.
AB  - BACKGROUND: Patients often complain about insufficient sleep or chronic insomnia
      in the belief that they need 8 hours of sleep. Treatment strategies may be guided
      by what sleep durations predict optimal survival and whether insomnia might
      signal mortality risks. METHODS: In 1982, the Cancer Prevention Study II of the
      American Cancer Society asked participants about their sleep duration and
      frequency of insomnia. Cox proportional hazards survival models were computed to
      determine whether sleep duration or frequency of insomnia was associated with
      excess mortality up to 1988, controlling simultaneously for demographics, habits,
      health factors, and use of various medications. RESULTS: Participants were more
      than 1.1 million men and women from 30 to 102 years of age. The best survival was
      found among those who slept 7 hours per night. Participants who reported sleeping
      8 hours or more experienced significantly increased mortality hazard, as did
      those who slept 6 hours or less. The increased risk exceeded 15% for those
      reporting more than 8.5 hours sleep or less than 3.5 or 4.5 hours. In contrast,
      reports of "insomnia" were not associated with excess mortality hazard. As
      previously described, prescription sleeping pill use was associated with
      significantly increased mortality after control for reported sleep durations and
      insomnia. CONCLUSIONS: Patients can be reassured that short sleep and insomnia
      seem associated with little risk distinct from comorbidities. Slight risks
      associated with 8 or more hours of sleep and sleeping pill use need further
      study. Causality is unproven.

PMID- 11825134
TI  - Can sleep be bad for you? Can insomnia be good?

PMID- 11825135
TI  - Association between self-reported childhood sexual abuse and adverse psychosocial
      outcomes: results from a twin study.
AB  - BACKGROUND: Increased risk for serious adverse outcomes has been associated with
      a history of childhood sexual abuse (CSA). Whether these risks are directly
      attributable to CSA rather than family background remains controversial. METHODS:
      Structured psychiatric telephone interviews were conducted from February 1996 to
      September 2000 with both members of 1991 same-sex pairs (1159 female and 832 male
      pairs) from a young adult Australian volunteer twin panel (mean [SD] age, 29.9
      [2.5] years). A binary composite CSA variable was constructed from responses to 5
      component questions. The association between CSA and adverse psychosocial
      outcomes was examined, controlling for family background. RESULTS: A history of
      CSA, reported by 16.7% of the women and 5.4% of the men, was more common among
      those reporting parental alcohol-related problems. Significantly increased risk
      was observed in women reporting a history of CSA for subsequently occurring major
      depression, suicide attempt, conduct disorder, alcohol dependence, nicotine
      dependence, social anxiety, rape after the age of 18 years, and divorce; most
      similar risks reached statistical significance in men. The greatest risks were
      associated with CSA involving intercourse. Childhood sexual abuse-negative twins
      (ie, those who denied having experienced CSA) from CSA-discordant pairs compared
      with other CSA-negative individuals had increased risk for many adverse outcomes
      suggesting correlated family background risk factors. Childhood sexual abuse
      positive members (ie, those who reported having experienced CSA) of CSA
      discordant pairs had significantly greater risk for all 8 examined adverse
      outcomes than their co-twins. CONCLUSIONS: Self-reported CSA was associated with
      increased risk for adverse outcomes, controlling for family background. Family
      background risk factors also were associated with adverse outcome risk.
      Discordant pair analysis seems to provide an effective means of controlling for
      family background risk factors.

PMID- 11825136
TI  - Visual perceptual and working memory impairments in schizophrenia.
AB  - BACKGROUND: Impairments in working memory have been proposed to underlie a broad
      range of cognitive deficits seen in schizophrenia. Visual working memory
      impairments are frequently reported in schizophrenia. Investigations of visual
      working memory generally assume intact visual information processing, despite
      evidence of visual perceptual impairments in schizophrenia. In this study, we
      evaluated the integrity of the perceptual system for object and spatial visual
      information and the relevant working memory system, after adjusting for
      individual perceptual performance differences. METHODS: Thirty patients with
      schizophrenia and 20 healthy control subjects underwent testing using a task of
      perceptual discrimination of spatial and object visual stimuli. For testing
      visual working memory, a delay was introduced to the perceptual discrimination
      task. A thresholding procedure was used so that each subject adequately perceived
      the information during the working memory test. RESULTS: Subjects with
      schizophrenia exhibited impaired performance relative to controls for object and
      spatial visual perceptual discrimination. The extent of impairment was greater
      for the object than for the spatial test. After controlling for perceptual
      impairments, the subjects with schizophrenia exhibited impaired performance
      relative to controls for the spatial working memory test but not the object
      working memory test. CONCLUSIONS: Findings implicate dysfunction of posterior
      brain areas that mediate visual perceptual processing and the prefrontal areas
      involved in the active maintenance of information during delay intervals.
      However, the systems that govern object and spatial visual perception and working
      memory appear to be affected differentially by schizophrenia.

PMID- 11825137
TI  - Impact of normal sexual dimorphisms on sex differences in structural brain
      abnormalities in schizophrenia assessed by magnetic resonance imaging.
AB  - BACKGROUND: Previous studies suggest that the impact of early insults
      predisposing to schizophrenia may have differential consequences by sex. We
      hypothesized that brain regions found to be structurally different in normal men
      and women (sexual dimorphisms) and abnormal in schizophrenia would show
      significant sex differences in brain abnormalities, particularly in the cortex,
      in schizophrenia. METHODS: Forty outpatients diagnosed as having schizophrenia by
      DSM-III-R were systematically sampled to be comparable within sex with 48 normal
      comparison subjects on the basis of age, ethnicity, parental socioeconomic
      status, and handedness. A comprehensive assessment of the entire brain was based
      on T1-weighted 3-dimensional images acquired from a 1.5-T magnet. Multivariate
      general linear models for correlated data were used to test for sex-specific
      effects regarding 22 hypothesized cortical, subcortical, and cerebrospinal fluid
      brain volumes, adjusted for age and total cerebrum size. Sex x group interactions
      were also tested on asymmetries of the planum temporale, Heschl's gyrus, and
      superior temporal gyrus, additionally controlled for handedness. RESULTS: Normal
      patterns of sexual dimorphisms were disrupted in schizophrenia. Sex-specific
      effects were primarily evident in the cortex, particularly in the frontomedial
      cortex, basal forebrain, cingulate and paracingulate gyri, posterior
      supramarginal gyrus, and planum temporale. Normal asymmetry of the planum was
      also disrupted differentially in men and women with schizophrenia. There were no
      significant differential sex effects in subcortical gray matter regions or
      cerebrospinal fluid. CONCLUSION: Factors that produce normal sexual dimorphisms
      may be associated with modulating insults producing schizophrenia, particularly
      in the cortex.

PMID- 11825138
TI  - Improving employment outcomes for persons with severe mental illnesses.
AB  - BACKGROUND: Unemployment remains a major consequence of schizophrenia and other
      severe mental illnesses. This study assesses the effectiveness of the Individual
      Placement and Support model of supportive employment relative to usual
      psychosocial rehabilitation services for improving employment among inner-city
      patients with these disorders. METHODS: Two hundred nineteen outpatients with
      severe mental illnesses, 75% with chronic psychoses, from an inner-city catchment
      area were randomly assigned to either the Individual Placement and Support
      program or a comparison psychosocial rehabilitation program. Participants
      completed a battery of assessments at study enrollment and every 6 months for 2
      years. Employment data, including details about each job, were collected weekly.
      RESULTS: Individual Placement and Support program participants were more likely
      than the comparison patients to work (42% vs 11%; P<.001; odds ratio, 5.58) and
      to be employed competitively (27% vs 7%; P<.001; odds ratio, 5.58). Employment
      effects were associated with significant differences in cumulative hours worked
      (t(211) = -5.0, P =.00000003) and wages earned (t = -5.5, P =.00000003). Among
      those who achieved employment, however, there were no group differences in time
      to first job or in number or length of jobs held. Also, both groups experienced
      difficulties with job retention. CONCLUSIONS: As hypothesized, the Individual
      Placement and Support program was more effective than the psychosocial
      rehabilitation program in helping patients achieve employment goals. Achieving
      job retention remains a challenge with both interventions.

PMID- 11825139
TI  - Prefrontal cortical volume in childhood-onset major depression: preliminary
      findings.
AB  - BACKGROUND: Abnormalities in the prefrontal cortex have been implicated in the
      pathogenesis of major depressive disorder (MDD). To our knowledge, no prior study
      has examined prefrontal cortical anatomy in pediatric patients with MDD near the
      onset of illness before receiving treatment. METHODS: Volumetric magnetic
      resonance imaging studies were conducted in 22 psychotropic-naive patients with
      MDD, aged 9 to 17 years (10 males and 12 females), and 22 case-matched healthy
      comparison control subjects. Twelve of the 22 patients with MDD had at least 1
      first-degree relative with MDD (familial MDD), whereas 10 had no clear family
      history of MDD (nonfamilial MDD). RESULTS: Patients with nonfamilial MDD had
      significantly larger left-sided but not right-sided prefrontal cortical volumes
      than patients with familial MDD (17% larger) and controls (11% larger). Left
      sided and right-sided prefrontal cortical volumes did not differ significantly
      between patients with familial MDD and controls. CONCLUSIONS: These results
      provide new evidence of prefrontal cortical alterations in pediatric MDD that may
      differ in familial and nonfamilial subtypes of MDD. Our findings must be
      considered preliminary, however, in view of the small sample size.

PMID- 11825140
TI  - Respiration in children at risk for panic disorder.

PMID- 11825144
TI  - Olanzapine in acute bipolar mania.

PMID- 11825142
TI  - The role of hypothalamic-pituitary-adrenal axis dysfunction in the attenuated
      growth hormone response in adolescents with familial loading for affective
      disorder.

PMID- 11825146
TI  - Medical quality assessment by scoring adherence to guideline intentions.
AB  - Quality assessment of clinician actions and patient outcomes is a central problem
      in guideline- or standards-based medical care. In this paper we describe an
      approach for evaluating and consistently scoring clinician adherence to medical
      guidelines using the intentions of guideline authors. We present the Quality
      Indicator Language (QUIL) that may be used to formally specify quality
      constraints on physician behavior and patient outcomes derived from medical
      guidelines. We present a modeling and scoring methodology for consistently
      evaluating multi-step and multi-choice guideline plans based on guideline
      intentions and their revisions.

PMID- 11825147
TI  - Using GEM-encoded guidelines to generate medical logic modules.
AB  - Among the most effective strategies for changing the process and outcomes of
      clinical care are those that make use of computer-mediated decision support. A
      variety of representation models that facilitate computer-based implementation of
      medical knowledge have been published, including the Guideline Elements Model
      (GEM) and the Arden Syntax for Medical Logic Modules (MLMs). We describe an XML
      based application that facilitates automated generation of partially populated
      MLMs from GEM-encoded guidelines. These MLMs can be further edited and shared
      among Arden-compliant information systems to provide decision support. Our work
      required three steps: (a) Knowledge extraction from published guideline documents
      using GEM, (b) Mapping GEM elements to the MLM slots, and (c) XSL transformation
      of the GEM-encoded guideline. Processing of a sample guideline generated 15 MLMs,
      each corresponding to a conditional or imperative element in the GEM structure.
      Mechanisms for linking various MLMs are necessary to represent the complexity of
      logic typical of a guideline.

PMID- 11825148
TI  - Combining decision support methodologies to diagnose pneumonia.
AB  - OBJECTIVE: To evaluate the performance of a computerized decision support system
      that combines two different decision support methodologies (a Bayesian network
      and a natural language understanding system) for the diagnosis of patients with
      pneumonia. DESIGN: Evaluation study using data from a prospective, clinical
      study. PATIENTS: All patients 18 years and older who presented to the emergency
      department of a tertiary care setting and whose chest x-ray report was available
      during the encounter. METHODS: The computerized decision support system
      calculated a probability of pneumonia using information provided by the two
      systems. Outcome measures were the area under the receiver operating
      characteristic curve, sensitivity, specificity, predictive values, likelihood
      ratios, and test effectiveness. RESULTS: During the 3-month study period there
      were 742 patients (45 with pneumonia). The area under the receiver operating
      characteristic curve was 0.881 (95% CI: 0.822, 0.925) for the Bayesian network
      alone and 0.916 (95% CI: 0.869, 0.949) for the Bayesian network combined with the
      natural language understanding system (p=0.01). CONCLUSION: Combining decision
      support methodologies that process information stored in different data formats
      can increase the performance of a computerized decision support system.

PMID- 11825149
TI  - Effective mapping of biomedical text to the UMLS Metathesaurus: the MetaMap
      program.
AB  - The UMLS Metathesaurus, the largest thesaurus in the biomedical domain, provides
      a representation of biomedical knowledge consisting of concepts classified by
      semantic type and both hierarchical and non-hierarchical relationships among the
      concepts. This knowledge has proved useful for many applications including
      decision support systems, management of patient records, information retrieval
      (IR) and data mining. Gaining effective access to the knowledge is critical to
      the success of these applications. This paper describes MetaMap, a program
      developed at the National Library of Medicine (NLM) to map biomedical text to the
      Metathesaurus or, equivalently, to discover Metathesaurus concepts referred to in
      text. MetaMap uses a knowledge intensive approach based on symbolic, natural
      language processing (NLP) and computational linguistic techniques. Besides being
      applied for both IR and data mining applications, MetaMap is one of the
      foundations of NLM's Indexing Initiative System which is being applied to both
      semi-automatic and fully automatic indexing of the biomedical literature at the
      library.

PMID- 11825150
TI  - A diffusion of innovations model of physician order entry.
AB  - OBJECTIVE: To interpret the results of a cross-site study of physician order
      entry (POE) in hospitals using a diffusion of innovations theory framework.
      METHODS: Qualitative study using observation, focus groups, and interviews. Data
      were analyzed by an interdisciplinary team of researchers using a grounded
      approach to identify themes. Themes were then interpreted using classical
      Diffusion of Innovations (DOI) theory as described by Rogers [1]. RESULTS: Four
      high level themes were identified: organizational issues; clinical and
      professional issues; technology implementation issues; and issues related to the
      organization of information and knowledge. Further analysis using the DOI
      framework indicated that POE is an especially complex information technology
      innovation when one considers communication, time, and social system issues in
      addition to attributes of the innovation itself. CONCLUSION: Implementation
      strategies for POE should be designed to account for its complex nature. The
      ideal would be a system that is both customizable and integrated with other parts
      of the information system, is implemented with maximum involvement of users and
      high levels of support, and is surrounded by an atmosphere of trust and
      collaboration.

PMID- 11825151
TI  - Finding appropriate clinical trials: evaluating encoded eligibility criteria with
      incomplete data.
AB  - We describe our work on creating a system that selects appropriate clinical
      trials by automating the evaluation of eligibility criteria. We developed a data
      model of eligibility for breast cancer clinical trials, upon which the criteria
      were encoded. Standard vocabularies are utilized to represent concepts used in
      the system, and retrieve their hierarchical relationships. The system
      incorporates Bayesian networks to handle missing patient information. Protocols
      are ranked by the belief that the patient is eligible for each of them. In a
      preliminary evaluation, we found good agreement (kappa 0.86) between the system
      and an independent physician in selection of protocols, but poor agreement (kappa
      0.24) in protocol ranking. We conclude that our approach is feasible, and
      potentially useful in assisting both physicians and patients in the task of
      selecting appropriate trials.

PMID- 11825152
TI  - A computer based intervention on the appropriate use of arterial blood gas.
AB  - OBJECTIVE: To evaluate impact of a computer-based intervention on arterial blood
      gas (ABG) usage in an intensive care setting. DESIGN: Retrospectively examined,
      via mixed group analysis, the effects of the intervention on ABG usage in the
      intensive care unit (ICU). SUBJECTS: Included all clinicians who placed ABG
      orders in an ICU using the computerized physician order-entry system, as well as
      controls in non-order entry units. METHODS: Computer-based intervention
      presenting ordering clinician with patient s previous ABG values and limiting
      forward duration of tests ordered. Study spanned 12 weeks, 5 weeks pre
      intervention and 7-weeks post-intervention. Of 8 ICUs, intervention implemented
      in 6, not implemented in 2. Data analyzed using the repeated measure ANOVA.
      RESULTS: Physicians entered <40% ABG orders. 376 ABGs per week processed pre
      intervention, 387 per week post. Results nonsignificant with a p= 0.09. Orders
      placed declined from 1039 per week, Jan 2000 to 662 per week, April 2001.
      DISCUSSION: Study did not demonstrate significant change; limited power. Need
      longer study periods. Impact improved in the future by targeting physician users
      and tailoring intervention to specific work flow pattern of high utilization
      units.

PMID- 11825153
TI  - Why British GPs use computers and hospital doctors do not.
AB  - Almost all general medical practitioners (GPs) in the UK use computers, compared
      with less than one in ten of hospital doctors. This paper explains how this
      unexpected situation came about over a thirty-year period, identifying some of
      the successes and failures of British medical computing along the way. Twelve
      separate factors are considered. The major determinants have not been technical,
      but rather a strong tide of political backing for general practice and leadership
      from the profession at the highest level, which have combined to build an
      appropriate regulatory framework and financial incentives that have encouraged
      GPs to embrace computers. Hospital computing has some difficulties not met by
      GPs, but the main factor preventing progress has been the lack of any real
      incentive   positive (carrot) or negative (stick), for hospital doctors to use
      computers.

PMID- 11825154
TI  - MedlineQBE (Query-by-Example).
AB  - Medline has the potential to significantly improve medical care but effective
      information retrieval remains difficult. Custom interfaces and relevance feedback
      are two approaches that have been successfully used to improve information
      retrieval. There are, however, many ways to implement these approaches. A system
      that facilitates rapid implementation and evaluation of novel algorithms has the
      potential to speed research progress. This paper describes MedlineQBE, a research
      workbench for implementing and evaluating information retrieval strategies. User
      interface, database access and display of results are abstracted leaving
      developers with the task of coding only the algorithm of interest. We implemented
      several custom interfaces, search-refinement strategies and a result-ordering
      algorithm using MedlineQBE. Preliminary evaluations of an oncology-patient
      interface and a relevance feedback algorithm that builds upon PubMed's "related
      articles" feature are promising. We conclude that custom interfaces and novel
      relevance feedback strategies have the potential to improve information retrieval
      from Medline.

PMID- 11825155
TI  - Circular hierarchical relationships in the UMLS: etiology, diagnosis, treatment,
      complications and prevention.
AB  - The Unified Medical Language System (UMLS) is a large repository of some 800,000
      concepts for the biomedical domain, organized by several millions of inter
      concept relationships, either inherited from the source vocabularies, or
      specifically generated. This paper focuses on hierarchical relationships in the
      UMLS Metathesaurus, and especially, on circular hierarchical relationships. Using
      the metaphor of a disease, we first analyze the causal mechanisms for circular
      hierarchical relationships. Then, we discuss methods to identify and remove these
      relationships. Finally, we briefly discuss the consequences of these
      relationships for applications based on the UMLS, and we propose some prevention
      measures.

PMID- 11825156
TI  - Informatics application provides instant research to practice benefits.
AB  - A web-based research information system was designed to enable our research team
      to efficiently measure health related quality of life among frail older adults in
      a variety of health care settings (home care, nursing homes, assisted living,
      PACE). The structure, process, and outcome data is collected using laptop
      computers and downloaded to a SQL database. Unique features of this project are
      the ability to transfer research to practice by instantly sharing individual and
      aggregate results with the clinicians caring for these elders and directly
      impacting the quality of their care. Clinicians can also dial in to the database
      to access standard queries or receive customized reports about the patients in
      their facilities. This paper will describe the development and implementation of
      the information system. The conference presentation will include a demonstration
      and examples of research to practice benefits.

PMID- 11825157
TI  - Does size matter?--Evaluation of value added content of two decades of successive
      coding schemes in secondary care.
AB  - Over the last two decades there has been a gradual evolution from the use of
      simple coding schemes to controlled clinical terminologies within clinical
      information systems in secondary care. This evolution has required significant
      resources in both the development of the different coding schemes and the cost of
      hardware, software and human effort in implementation. During this time there has
      been successively larger and more complex coding schemes available for use in the
      UK Health Service: Read Codes 4 byte set, Read Codes 5 byte set, ICD-10 and
      Clinical Terms Version 3. This study evaluates what added value these successive
      coding schemes have offered in terms of content coverage by testing concepts
      derived from aClinical Information System (CIS) that has been in use to support
      diabetic care since 1973 (Diabeta). The schemes are quantitatively evaluated by
      measuring their success in providing a concept match for every notion from the
      CIS and their relative merits are compared. Significant added value has accrued
      over the years in completeness of the schemes reflected in their increased size.
      There appears to be justification for the continued development of clinical
      terminologies to support secondary care.

PMID- 11825158
TI  - Usability evaluation of the progress note construction set.
AB  - OVERVIEW: The Veterans Administration (VA) Computerized Patient Record System
      (CPRS) is a nationally deployed software product that integrates provider order
      entry, progress notes, vitals, consults, discharge summaries, problem lists,
      medications, labs, radiology, transcribed documents, study reports, and clinical
      reminders. Users rapidly adopted the graphical user interface for data retrieval,
      but demanded options to typing for data entry. We programmed "point and click"
      forms that integrate with CPRS individually, but were soon overwhelmed by
      requests. Subsequently, we developed the Progress Note Construction Set (PNCS); a
      tool suite that permits subject matter experts without programming skills to
      create reusable "point and click" forms. In this study, we evaluate the usability
      of these user-constructed forms. METHODS: An untrained, non-VA subject matter
      expert used the PNCS to create a graphical form for "skin tear" documentation.
      Ten VA nurses used the skin tear form to document findings for 7 standardized
      clinical scenarios. Following each scenario the subjects answered usability
      questions about the form. RESULTS: The subject matter expert created the skin
      tear form in 78 minutes. Users found the form to facilitate their data entry (p
      0.0265), and to be at least as fast (p 0.0029) and as easy to use as expected (p
      0.0166). Average note entry time was 3.4 minutes. CONCLUSION: The PNCS allowed a
      non-programmer to quickly create a usable, CPRS-integrated point and click form.
      Users found the subject matter expert s form fast and easy to use. The tool suite
      is a more scaleable form creation method because capacity is no longer limited by
      programmer availability.

PMID- 11825159
TI  - Mobile technologies in the management of disasters: the results of a telemedicine
      solution.
AB  - Nowadays a great number of applications are used to compile and transmit
      casualties and disasters information but there are many troubles associated with
      the technology as can be the communications reliability and the size and weight
      of the devices medical staff has to carry with. Telecommunication infrastructures
      support information movement among geographically dispersed locations. Recently a
      large family of little devices has appeared in the buyer's market. They are
      called Personal Digital Assistants and because of their physic and technical
      features, they are very useful in the emergency field. As for the communications
      reliability, many technologies have been developed in the last years but it is
      necessary to find a solution that can be used in whatever situation independently
      of the emergency circumstances. Facing this reality, the Spanish government
      funded REMAF, an ATYCA (Initiative of Support for the Technology, Security and
      Quality in the Industry) project. REMAF joined research groups (UPM), phone
      operators (Fundacion Airtel Movil) and end users (SAMUR) to build a disaster data
      management system conceived to use modern telemedicine systems to optimize the
      management in these situations, taking the advantage of the above mentioned
      mobile communication tools and networks.

PMID- 11825160
TI  - Comparing syntactic complexity in medical and non-medical corpora.
AB  - With the growing use of Natural Language Processing (NLP) techniques as solutions
      in Medical Informatics, the need to quickly and efficiently create the knowledge
      structures used by these systems has grown concurrently. Automatic discovery of a
      lexicon for use by an NLP system through machine learning will require
      information about the syntax of medical language. Understanding the syntactic
      differences between medical and non-medical corpora may allow more efficient
      acquisition of a lexicon. Three experiments designed to quantify the syntactic
      differences in medical and non-medical corpora were conducted. The results show
      that the syntax of medical language shows less variation than non-medical
      language and is likely simpler. The differences were great enough to question the
      applicability of general language tools on medical language. These differences
      may reduce the difficulty of some free text machine learning problems by
      capitalizing on the simpler nature of narrative medical syntax.

PMID- 11825162
TI  - Development of a Personal Digital Assistant (PDA) based client/server NICU
      patient data and charting system.
AB  - Personal Digital Assistants (PDAs) offer clinicians the ability to enter and
      manage critical information at the point of care. Although PDAs have always been
      designed to be intuitive and easy to use, recent advances in technology have made
      them even more accessible. The ability to link data on a PDA (client) to a
      central database (server) allows for near-unlimited potential in developing point
      of care applications and systems for patient data management. Although many stand
      alone systems exist for PDAs, none are designed to work in an integrated
      client/server environment. This paper describes the design, software and hardware
      selection, and preliminary testing of a PDA based patient data and charting
      system for use in the University of Washington Neonatal Intensive Care Unit
      (NICU). This system will be the subject of a subsequent study to determine its
      impact on patient outcomes and clinician efficiency.

PMID- 11825161
TI  - What's so special about medications: a pharmacist's observations from the POE
      study.
AB  - Observations from a multi-site observational study of physician order entry (POE)
      confirm that implementing POE is problematic, and suggest that implementing
      medication order entry is particularly difficult. A pharmacist participating in
      the study group sought to answer the question: What makes medications different?
      Analysis of themes specific to medication POE in this study's large data set was
      undertaken using a grounded theory approach. Emerging themes in the data are
      explored and include: (1) order complexity and the consequences of error; (2)
      impacts on professional roles; (3) prescribing needs in different settings; and
      (4) technology impact on medication administration. Awareness of potential
      roadblocks and lessons learned from previous implementation attempts should help
      organizations considering medication POE to optimize their own strategies.

PMID- 11825163
TI  - Evaluation of negation phrases in narrative clinical reports.
AB  - OBJECTIVE: Automatically identifying findings or diseases described in clinical
      textual reports requires determining whether clinical observations are present or
      absent. We evaluate the use of negation phrases and the frequency of negation in
      free-text clinical reports. METHODS: A simple negation algorithm was applied to
      ten types of clinical reports (n=42,160) dictated during July 2000. We counted
      how often each of 66 negation phrases was used to mark a clinical observation as
      absent. Physicians read a random sample of 400 sentences, and precision was
      calculated for the negation phrases. We measured what proportion of clinical
      observations were marked as absent. RESULTS: The negation algorithm was triggered
      by sixty negation phrases with just seven of the phrases accounting for 90% of
      the negations. The negation phrases received an overall precision of 97%, with
      "not" earning the lowest precision of 63%. Between 39% and 83% of all clinical
      observations were identified as absent by the negation algorithm, depending on
      the type of report analyzed. The most frequently used clinical observations were
      negated the majority of the time. CONCLUSION: Because clinical observations in
      textual patient records are frequently negated, identifying accurate negation
      phrases is important to any system processing these reports.

PMID- 11825165
TI  - Integration of nursing assessment concepts into the medical entities dictionary
      using the LOINC semantic structure as a terminology model.
AB  - Recent investigations have tested the applicability of various terminology models
      for the representing nursing concepts including those related to nursing
      diagnoses, nursing interventions, and standardized nursing assessments as a
      prerequisite for building a reference terminology that supports the nursing
      domain. We used the semantic structure of Clinical LOINC (Logical Observations,
      Identifiers, Names, and Codes) as a reference terminology model to support the
      integration of standardized assessment terms from two nursing terminologies into
      the Medical Entities Dictionary (MED), the concept-oriented, metadata dictionary
      at New York Presbyterian Hospital. Although the LOINC semantic structure was used
      previously to represent laboratory terms in the MED, selected hierarchies and
      semantic slots required revisions in order to incorporate the nursing assessment
      concepts. This project was an initial step in integrating nursing assessment
      concepts into the MED in a manner consistent with evolving standards for
      reference terminology models. Moreover, the revisions provide the foundation for
      adding other types of standardized assessments to the MED.

PMID- 11825164
TI  - A metadata framework for interoperating heterogeneous genome data using XML.
AB  - The rapid advances in the Human Genome Project and genomic technologies have
      produced massive amounts of data populated in a large number of network
      accessible databases. These technological advances and the associated data can
      have a great impact on biomedicine and healthcare. To answer many of the
      biologically or medically important questions, researchers often need to
      integrate data from a number of independent but related genome databases. One
      common practice is to download data sets (text files) from various genome Web
      sites and process them by some local programs. One main problem with this
      approach is that these programs are written on a case-by-case basis because the
      data sets involved are heterogeneous in structure. To address this problem, we
      define metadata that maps these heterogeneously structured files into a common
      eXtensible Markup Language (XML) structure to facilitate data interoperation. We
      illustrate this approach by interoperating two sets of essential yeast genes that
      are stored in two yeast genome databases (MIPS and YPD).

PMID- 11825166
TI  - Battling Scylla and Charybdis: the search for redundancy and ambiguity in the
      2001 UMLS metathesaurus.
AB  - I previously developed methods for identifying cases of multiple synonymous
      concepts (redundancy) and concepts with multiple meanings (ambiguity) and applied
      them to the 1995 UMLS Metathesaurus. These methods use semantic approaches
      (including knowledge about word synonymy and the semantic types assigned to
      concepts) to complement the standard lexical approaches. In this paper, I
      describe the results of their application to the 2001 Metathesaurus and examine
      their implications for the evolution of the UMLS.

PMID- 11825168
TI  - A formal method to resolve temporal mismatches in clinical databases.
AB  - Overcoming data heterogeneity is essential to the transfer of decision-support
      programs to legacy databases and to the integration of data in clinical
      repositories. Prior methods have focused primarily on problems of differences in
      terminology and patient identifiers, and have not addressed formally the problem
      of temporal data heterogeneity, even though time is a necessary element in
      storing, manipulating, and reasoning about clinical data. In this paper, we
      present a method to resolve temporal mismatches present in clinical databases.
      This method is based on a foundational model of time that can formalize various
      temporal representations. We use this temporal model to define a novel set of
      twelve operators that can map heterogeneous time-stamped data into a uniform
      temporal scheme. We present an algorithm that uses these mapping operators, and
      we discuss our implementation and evaluation of the method as a software program
      called Synchronus.

PMID- 11825167
TI  - Development of visual diagnostic expertise in pathology.
AB  - In this study, we use methods from information-processing to explore the visual
      diagnostic processes of novice, intermediate, and expert pathologists. Subjects
      were asked to examine and interpret a set of slides while we collected think
      aloud verbal protocols and captured on digital video the actual visual data they
      examined from the microscope. We performed an in-depth combined video and
      protocol-based analysis of processes and errors occurring as the task was
      performed. Additionally, we collected measures of accuracy, certainty, and
      difficulty for all cases. Our preliminary analysis identified significant
      differences between groups in all three major aspects of this task: searching
      skills, perceptual skills and cognitive/reasoning skills. We describe the
      implications of our preliminary cognitive task analysis on the design of a
      developing intelligent educational system in Pathology.

PMID- 11825169
TI  - The nature of communication in virtual home care visits.
AB  - The study's objective was to analyze "virtual" home care visits that utilize
      telemedicine technology and to investigate the type and quality of interaction
      between provider and patient. The setting was the TeleHomeCare Project which
      provides TV-based videoconferencing. Patients are receiving standard home care
      services with an addition of virtual visits. 122 virtual visits were reviewed and
      a content analysis was performed for 30 of these. Time was apportioned among the
      following categories of communication: assessing the patient's clinical status,
      promoting compliance, addressing psychosocial issues, general informal talk,
      education, administrative issues, technical issues, assessing patient
      satisfaction and ensuring accessibility. The findings indicate that technology
      does not interfere with but rather enriches the care process. Although there are
      activities that cannot be conducted in virtual visits, they can address most of
      the important aspects of care delivery giving strength to the argument that they
      could in some cases substitute traditional visits.

PMID- 11825170
TI  - The SNOMED RT Procedure Model.
AB  - BACKGROUND: SNOMED RT represents a fundamental change from prior versions of
      SNOMED. The logic-based structure of SNOMED RT enables concepts to be defined
      more explicitly, providing an opportunity to address inconsistencies and
      ambiguities present in prior SNOMED concept definitions. OBJECTIVES: Create a
      unifying organizational strategy for all SNOMED RT procedures, and remove
      ambiguities in procedure concept definitions. METHODS: A comprehensive model of
      procedures was developed, based on a set of guiding principles and a review of
      known existing models. RESULTS: All SNOMED RT procedures are categorized by a
      common set of "root procedures" (high level atomic actions), and are more
      explicitly defined by a shared set of defining relationships. CONCLUSIONS: While
      the objectives have largely been met, open issues continue to be addressed. The
      similarity between procedure models of SNOMED RT and the U.K. s Clinical Terms
      Version 3 is proving to greatly facilitate the full integration of the two
      terminologies into a merged vocabulary to be known as SNOMED Clinical Terms
      (SNOMED CT), slated to be released in the near future.

PMID- 11825171
TI  - Disambiguation data: extracting information from anonymized sources.
AB  - Privacy protection is an important consideration when releasing medical databases
      to the research community. We show that while recent advances in anonymization
      algorithms provide increased levels of protection, it is still possible to
      calculate approximations to the original data set. In some cases, one can even
      uniquely reconstruct entries in a table before anonymization. In this paper, we
      demonstrate how knowledge of an anonymization algorithm based on ambiguating data
      cell entries can be used to undo the anonymization process. We investigate the
      effect of this algorithm and its reversal on data sets of varying sizes and
      distributions. It is shown that by using a computationally complex disambiguation
      process, information on individuals can be extracted from an anonymized data set.

PMID- 11825172
TI  - Integrated web-based viewing and secure remote access to a clinical data
      repository and diverse clinical systems.
AB  - The advent of the World-Wide-Web protocols and client-server technology has made
      it easy to build low-cost, user-friendly, platform-independent graphical user
      interfaces to health information systems and to integrate the presentation of
      data from multiple systems. The authors describe a Web interface for a clinical
      data repository (CDR) that was moved from concept to production status in less
      than six months using a rapid prototyping approach, multi-disciplinary
      development team, and off-the-shelf hardware and software. The system has since
      been expanded to provide an integrated display of clinical data from nearly 20
      disparate information systems.

PMID- 11825173
TI  - A randomized controlled trial of the accuracy of clinical record retrieval using
      SNOMED-RT as compared with ICD9-CM.
AB  - BACKGROUND: Concept-based Indexing is purported to provide more granular data
      representation for clinical records.1,2 This implies that a detailed clinical
      terminology should be able to provide improved access to clinical records. To
      date there is no data to show that a clinical reference terminology is superior
      to a precoordinated terminology in its ability to provide access to the clinical
      record. Today, ICD9-CM is the most commonly used method of retrieving clinical
      records. OBJECTIVE: In this study, we compare the sensitivity, specificity,
      positive likelihood ratio, positive predictive value and accuracy of SNOMED-RT
      vs. ICD9-CM in retrieving ten diagnoses from a random sample of 2,022 episodes of
      care. METHOD: We randomly selected 1,014 episodes of care from the inpatient
      setting and 1,008 episodes of care from the outpatient setting. Each record had
      associated with it, the free text final diagnoses from the Master Sheet Index at
      the Mayo Clinic and the ICD9-CM codes used to bill for the encounters within the
      episode of care. The free text diagnoses were coded by two expert indexers
      (disagreements were addressed by a Staff Clinician) as to whether queries
      regarding one of 5 common or 5 uncommon diagnoses should return this encounter.
      The free text entries were automatically coded using the Mayo Vocabulary
      Processor. Each of the ten diagnoses was exploded in both SNOMED-RT and ICD9-CM
      and using these entry points, a retrieval set was generated from the underlying
      corpus of records. Each retrieval set was compared with the Gold Standard created
      by the expert indexers. RESULTS: SNOMED-RT produced significantly greater
      specificity in its retrieval sets (99.8% vs. 98.3%, p<0.001 McNemar Test). The
      positive likelihood ratios were significantly better for SNOMED-RT retrieval sets
      (264.9 vs. 33.8, p<0.001 McNemar Test). The positive predictive value of a SNOMED
      RT retrieval was also significantly better than ICD9-CM (92.9% vs. 62.4%, p<0.001
      McNemar Test). The accuracy defined as 1   (the total error rate (FP+FN) / Total
      # episodes queried (20,220)) was significantly greater for SNOMED-RT (98.2% vs.
      96.8%, p=0.002 McNemar Test). Interestingly, the sensitivity of the SNOMED-RT
      generated retrieval set was not significantly different from ICD9-CM, but there
      was a trend toward significance (60.4% vs. 57.6%, p=0.067 McNemar Test). However,
      if we examine only the outpatient practice SNOMED-RT produced a more sensitive
      retrieval set than ICD9-CM (54.8% vs. 46.4%, p=0.002 McNemar Test). CONCLUSIONS:
      Our data clearly shows that information regarding both common and rare disorders
      is more accurately identified with automated SNOMED-RT indexing using the Mayo
      Vocabulary Processor than it is with traditional hand picked constellations of
      codes using ICD9-CM. SNOMED-RT provided more sensitive retrievals of outpatient
      episodes of care than ICD9-CM.

PMID- 11825174
TI  - A metadata vocabulary for self- and third-party labeling of health web-sites:
      Health Information Disclosure, Description and Evaluation Language (HIDDEL).
AB  - We describe HIDDEL (Health Information Disclosure, Description and Evaluation
      Language), formerly known as medPICS (platform for Internet content selection in
      medicine), a metadata vocabulary designed to enhance transparency, trust and
      quality of health information on the web. The vocabulary may be used (1) by
      webmasters to self-describe their contents and policies; (2) by infomediaries
      (e.g. Healthfinder, NHS Direct/NeLH), e.g. third party evaluators, rating or
      portal services, to annotate other websites; (3) and by users, to describe their
      preferences. As an XML application it conforms to the W3C's RDF Specification.
      The metadata vocabulary is primarily intended to enable descriptions of whole
      health websites or health information providers. The vocabulary is designed to
      provide a computer-readable electronic "label" of a health website, telling users
      who is behind the website, how the website is sponsored, what the con-tent, aim
      and target audience is, how the information was compiled, what risks the service
      bears, or what people say about the resource. Client-software can "read" this
      label automatically, compare it to the user s own set of preferences and needs,
      and alert and advise users.

PMID- 11825175
TI  - Generation of pedigree diagrams for web display using scalable vector graphics
      from a clinical trials database.
AB  - The standard method of studying inherited disease is to observe its pattern of
      distribution in families, that is, its pattern in a pedigree. For clinical
      studies focused on inherited disease, a pedigree diagram is a valuable visual
      tool for the display of inheritance patterns. We describe the creation of a web
      based pedigree display module for Trial/DB, a Web accessible database developed
      at the Yale Center for Medical Informatics (YCMI) to support clinical research
      studies. The pedigree diagram is generated dynamically from the database. The
      icons representing each subject in the pedigree are selectable hyperlinks that
      will display detailed clinical data collected on the subject. Microsoft Active
      Server Page and Scalable Vector Graphics (SVG) are used to create the interactive
      pedigree diagrams.

PMID- 11825176
TI  - Publets: clinical judgement on the web.
AB  - The Internet is now a major channel for publishing medical research data and
      documents, including clinical practice guidelines. It is now possible to capture
      guidelines in a computer interpretable form opening up the capability of using
      the internet (and intra/extranets etc.) to deliver patient-specific advice and
      other services. A development lifecycle and technology for publishing and
      delivering services at the point of care ("publets") are described. As with all
      new technologies, however, these new methods entail risks as well as
      opportunities. The paper closes with a discussion of quality requirements and an
      argument that publets should include a safety case as an integral part of their
      content.

PMID- 11825177
TI  - Online pattern recognition in intensive care medicine.
AB  - In intensive care physiological variables of the critical-ly ill are measured and
      recorded in short time intervals. The existing alarm systems based on fixed
      thresholds produce a large number of false alarms. Usually the change of a
      variable over time is more informative than one pathological value at a
      particular time point. Intelligent alarm systems which detect important changes
      within a physiological time series are needed for suitable bedside decision
      support. There are various approaches to modeling time-dependent data and also
      several methodologies for pattern detection in time series. We compare several
      methodologies de-signed for online detection of measurement artifacts, level
      changes, and trends for a proper classification of the patient s state by means
      of a comparative case-study.

PMID- 11825178
TI  - Evaluating the UMLS as a source of lexical knowledge for medical language
      processing.
AB  - Medical language processing (MLP) systems rely on specialized lexicons in order
      to recognize, classify, and normalize medical terminology, and the performance of
      an MLP system is dependent on the coverage and quality of such lexicons. However,
      the acquisition of lexical knowledge is expensive and time-consuming. The UMLS is
      a comprehensive resource that can be used to acquire lexical knowledge needed for
      medical language processing. This paper describes methods that use these
      resources to automatically create lexical entries and generate two lexicons. The
      first lexicon was created primarily using the UMLS, whereas the second was
      created by supplementing the lexicon of an existing MLP system called MedLEE with
      entries based on the UMLS. We subsequently carried out a study, which is the
      primary focus of this paper, using MedLEE with each of the two lexicons and also
      the current MedLEE lexicon to measure performance. Overall accuracy, sensitivity,
      and specificity using the lexicon primarily based on the UMLS were.86,.60, and.96
      respectively. Those measures using the MedLEE lexicon alone were.93,.81, and.93,
      which was significantly better except for specificity; performance using the
      supplemental lexicon was exactly the same as performance using solely the MedLEE
      lexicon.

PMID- 11825180
TI  - Cross-tool communication: from protocol authoring to eligibility determination.
AB  - To be effective, informatics tools for clinical trial protocols must inter
      operate and share knowledge. We demonstrate a simple XML-based communication of
      eligibility criteria information between two independently-developed informatics
      tools. Using a shared DTD model of criteria, an authoring tool (developed within
      the Protege environment) can send a list of eligibility criteria to a commercial
      system for automatic eligibility determination (the "iKnowChart" system by
      iKnowMed). The criteria model, developed as a Protege ontology, includes both the
      terminology and the logic needed to compute eligibility for a given patient. As a
      demonstration of cross-tool communication, we have encoded criteria from an
      active clinical trial protocol (E1199), and shown how use of the authoring tool
      can effectively update the eligibility knowledge and the behavior of the
      commercial iKnowChart system. As part of the cross-tool knowledge sharing, we use
      Common Data Elements, an oncology terminology developed by the National Cancer
      Institute.

PMID- 11825179
TI  - Assessing physician attitudes regarding use of an outpatient EMR: a longitudinal,
      multi-practice study.
AB  - A pre- and post-implementation assessment of physician attitudes was undertaken
      as part of the evaluation of the pilot implementations of an outpatient EMR in 6
      practices of a large academic health system. Our results show that these
      physicians are ready adopters of computer technology when it demonstrates value
      added for the effort required to use it. These physicians utilize email, the
      Internet, remote access to computer systems, and personal productivity software
      because they serve a valuable purpose in their academic and clinical work and in
      their personal lives. Much more critical to the acceptance of an EMR by
      physicians is its ability to facilitate efficient clinical workflows without
      negative effects on the valued relationships physicians have with their patients-
      those that are based on rapport, quality of care, and privacy.

PMID- 11825181
TI  - An implementation framework for GEM encoded guidelines.
AB  - Access to timely decision support information is critical for delivery of high
      quality medical care. Transformation of clinical knowledge that is originally
      expressed in the form of a guideline to a computable format is one of the main
      obstacles to the integration of knowledge sharing functionality into computerized
      clinical systems. The Guideline Element Model (GEM) provides a methodology for
      such a transformation. Although the model has been used to store heterogeneous
      guideline knowledge, it is important to demonstrate that GEM markup facilitates
      guideline implementation. This report demonstrates the feasibility of
      implementation of GEM-encoded guideline recommendations using Apache Group s
      Cocoon Web Publishing Framework. We further demonstrate how XML-based programming
      allows for maintaining the separation of guideline content from processing logic
      and from presentation format. Finally, we analyze whether the guideline authors 
      original intent has been sufficiently captured and conveyed to the end user.

PMID- 11825182
TI  - Quality improvement in pediatric well care with an electronic record.
AB  - For the past 4 years the pediatric office of Children's Health Specialists has
      used an electronic medical record (EMR). The EMR has forms for the routine well
      child visits recommended by the American Academy of Pediatrics (AAP) [1] and
      instruction sheets with key information on development and safety as recommended
      by "Bright Futures" [2]. In this study the completeness of well visits,
      instruction distribution, immunizations and lead testing were examined for all
      children in our practice with birthdays in 1998. When children did get to the
      office they did get their instruction sheets on child development and safety and
      were well immunized. Children who had insurance coverage to pay for in-office
      lead testing were 42.6 times more likely to have blood lead testing done: Risk
      Ratio 42.6, lower limit 10.6, upper limit 171.3. Insurance coverage and
      regulatory changes would likely increase lead screening markedly in high risk
      populations. Our implementation of our EMR has helped us to deliver high quality
      pediatric well child care but external obstacles limit the completeness of the
      care.

PMID- 11825184
TI  - How to select a clinical information system.
AB  - Modern computer-based hospital information systems are mostly distributed with
      several information subsystems connected together by communication services. A
      single subsystem may be developed or purchased ("make" or "buy"). Before the
      purchase of hard- and software it is necessary to check out whether the product
      fits the requirements concerning the functionality and especially the integration
      in the hospital information system. This selection process is difficult and
      tedious and requires thus a simple and flexible technique. An appropriate
      approach for the comparison of clinical information systems before implementation
      based on the SMARTER method is described here, in hospital and its practicability
      is demonstrated with an example.

PMID- 11825183
TI  - Patient safety in guideline-based decision support for hypertension management:
      ATHENA DSS.
AB  - The Institute of Medicine recently issued a landmark report on medical error.1 In
      the penumbra of this report, every aspect of health care is subject to new
      scrutiny regarding patient safety. Informatics technology can support patient
      safety by correcting problems inherent in older technology; however, new
      information technology can also contribute to new sources of error. We report
      here a categorization of possible errors that may arise in deploying a system
      designed to give guideline-based advice on prescribing drugs, an approach to
      anticipating these errors in an automated guideline system, and design features
      to minimize errors and thereby maximize patient safety. Our guideline
      implementation system, based on the EON architecture, provides a framework for a
      knowledge base that is sufficiently comprehensive to incorporate safety
      information, and that is easily reviewed and updated by clinician-experts.

PMID- 11825185
TI  - An assessment of cancer clinical trials vocabulary and IT infrastructure in the
      U.S.
AB  - Twenty-three cancer research centers in the U.S. were assessed to determine data
      standards, vocabularies, and information infrastructure used in support of
      clinical trials. Eighteen of the 23 responded. Major findings were related to: 1)
      clinical trials infrastructure information, 2) current systems environment, 3)
      technical details, and 4) vocabulary and data standards. The size of the facility
      correlated with the quality, features and functionality of the clinical trials
      system (CTS). One facility had as many as 22 separate CTS. There were only 2
      sites that had integrated clinical information systems (CIS) with CTS. The
      responses included the major vocabularies and data standards used in CTS. The
      majority used some automation but many also reported manual data entry. CTS had
      more manual entry than CIS because of regulatory reporting requirements. The
      assessment identified opportunities for guidance in defining vocabularies and
      standards for cancer clinical trial systems in the US.

PMID- 11825186
TI  - Subword segmentation--leveling out morphological variations for medical document
      retrieval.
AB  - Many lexical items from medical sublanguages exhibit a complex morphological
      structure that is hard to account for by simple string matching (e.g.,
      truncation). While inflection is usually easy to deal with, productive
      morphological processes in terms of derivation and (single-word) composition
      constitute a real challenge. We here propose an approach in which morphologically
      complex word forms are segmented into medically significant subwords. After
      segmentation, both query terms and document terms are submitted to the matching
      procedure. This way, problems arising from morphologically motivated word form
      alterations can be eliminated from the retrieval procedure. We provide empirical
      data which reveals that subword-based indexing and retrieval performs
      significantly better than conventional string matching approaches.

PMID- 11825187
TI  - A metaschema of the UMLS based on a partition of its semantic network.
AB  - The Unified Medical Language System's (UMLS's) Semantic Network (SN) provides an
      important conceptual abstraction that helps orient users to the vast knowledge
      content of its Metathesaurus. However, the SN is itself large and complex, and
      can also benefit from an additional abstract view of its own. In this paper, we
      present a metaschema that serves such a purpose. This metaschema is derived from
      a previously developed partitioning methodology for the SN. The metaschema is
      formally defined, and used to provide partial compact views of the SN.

PMID- 11825188
TI  - Mediating between nursing intervention terminology systems.
AB  - The purpose of this study is to explore the use of formal systems as a way of
      mediating between diverse nursing intervention terminology systems. Existing
      approaches to mediation, such as the UMLS Metathesaurus, make heavy use of
      surface language. This compromises their capacity for managing similarities and
      differences between terminology systems. Within this study an initial ontology,
      derived from three existing terminology systems, was built using the GALEN
      approach. The ontology overcomes many of the barriers to effective mediation; it
      represents a rich integrated hierarchy that may be used to identify both direct
      and indirect mappings between concepts from diverse terminology systems. The
      approach used forms part of a formative, evolutionary development methodology in
      which potential mappings are validated and the results fed back into the next
      round of development.

PMID- 11825189
TI  - Virtual healthcare delivery: defined, modeled, and predictive barriers to
      implementation identified.
AB  - Provider organizations lack: 1. a definition of "virtual" healthcare delivery
      relative to the products, services, and processes offered by dot.coms, web
      compact disk healthcare content providers, telemedicine, and telecommunications
      companies, and 2. a model for integrating real and virtual healthcare delivery.
      This paper defines virtual healthcare delivery as asynchronous, outsourced, and
      anonymous, then proposes a 2x2 Real-Virtual Healthcare Delivery model focused on
      real and virtual patients and real and virtual provider organizations. Using this
      model, provider organizations can systematically deconstruct healthcare delivery
      in the real world and reconstruct appropriate pieces in the virtual world.
      Observed barriers to virtual healthcare delivery are: resistance to
      telecommunication integrated delivery networks and outsourcing; confusion over
      virtual infrastructure requirements for telemedicine and full-service web
      portals, and the impact of integrated delivery networks and outsourcing on extant
      cultural norms and revenue generating practices. To remain competitive provider
      organizations must integrate real and virtual healthcare delivery.

PMID- 11825190
TI  - Mining free-text medical records.
AB  - Text mining projects can be characterized along four parameters: 1) the demands
      of the market in terms of target domain and specificity and depth of queries; 2)
      the volume and quality of text in the target domain; 3) the text mining process
      requirements; and 4) the quality assurance process that validates the extracted
      data. In this paper, we provide lessons learned and results from a large-scale
      commercial project using Natural Language Processing (NLP) for mining the
      transcriptions of dictated clinical records in a variety of medical specialties.
      We conclude that the current state-of-the-art in NLP is suitable for mining
      information of moderate content depth across a diverse collection of medical
      settings and specialties.

PMID- 11825191
TI  - Presentation of problem-specific, text-based medical knowledge: XML and related
      technologies.
AB  - Systematic reviews of the impact of clinical decision support systems on provider
      behavior and patient outcome have shown evidence of benefit. Knowledge-based
      functions for decision support or monitoring that are integrated in clinical
      information systems are a potentially effective way. But these concepts are
      restricted by the efforts required for development and maintenance of the
      information systems and the limited number of implemented medical rules.
      Physicians are familiar to get their information from text-based sources. It
      seems to be straight-forward to rely on a document-based solution in order to
      present problem-specific information at the point of care. We have developed a
      concept for context-sensitive retrieving and presentation of text-based medical
      knowledge (textbook of internal medicine) using the eXtensible Markup Language
      (XML) and related technologies. This concept can facilitate the electronic query
      and presentation of this resource. XML may replace narrative text as a storage
      format and allows to structure the data in a stepwise fashion. On the basis of
      structured data we are able to improve the search quality for clinical
      information and its presentation which forms a crucial pre-requisite for the use
      of the information and the implementation of evidence-based care in the clinical
      routine.

PMID- 11825192
TI  - A critical pathway for electronic medical record selection.
AB  - Electronic medical records (EMRs) are increasingly becoming a necessary tool in
      health care. Given their potential to influence every aspect of health care,
      there has been surprisingly little rigorous research applied to this important
      piece of emerging health technology. An initial phase of the COMPETE study, which
      is examining the impact of EMRs on efficiency, quality of care and privacy
      concerns, involved a rigorous "critical pathway" approach to EMR selection for
      the study. A multidisciplinary team with clinical, technical and research
      expertise led an 8-stage evaluation process with direct input from user
      physicians at each stage. An iterative sequence of review of EMR specifications
      and features, live product demonstrations, site visits, and negotiations with
      vendors led to a progressive narrowing of the field of eligible EMR systems.
      Final scoring was based on 3 main themes of clinical usability, data quality and
      support/vendor issues. We believe that a rigorous, multidisciplinary process such
      as this is required to maximize success of any EMR implementation project.

PMID- 11825193
TI  - Consumer health informatics: a consensus description and commentary from American
      Medical Informatics Association members.
AB  - BACKGROUND: Although interest in Consumer Health Informatics (CHI) has increased,
      a consensus definition of CHI does not yet exist. PURPOSE: To conduct a
      hypothesis-generating survey of AMIA members regarding definition and research
      agenda for CHI. METHODS: We solicited participation among AMIA members in an
      Internet-based survey focusing on issues related to a definition of CHI. RESULTS:
      One hundred thirty-five AMIA members responded. Participants indicated a broad
      spectrum of topics important to CHI including "self-help for disease management"
      and "patient access to their own medical records." CHI research was felt to rely
      heavily on public health methods such as epidemiology and outcomes research, a
      paradigm shift from traditional medical informatics. Responses indicated a
      perceived lack of funding and need for further research in CHI. CONCLUSIONS: A
      working definition should emphasize the multidisciplinary nature of CHI, include
      consumer input into CHI design, and focus on public health approaches to
      evaluation.

PMID- 11825195
TI  - Enabling clinicians, researchers, and educators to build custom web-based
      biomedical information systems.
AB  - We describe an open-source toolkit that enables clinicians, researchers, and
      educators to build their own web-based biomedical information systems. The Web
      Interfacing Repository Manager (Wirm) is a high-level application server aimed at
      medical professionals, allowing them to create individually tailored systems for
      managing their multimedia data and knowledge. We provide an overview of the
      features of Wirm, explaining how they meet the requirements for supporting
      biomedical information management, and describe four applications that are
      currently being developed with Wirm: MyPACS, a teaching file authoring system for
      radiologists, Fathom, an experiment management system for natural language
      processing, the Digital Anatomist Repository, an image archiving tool for medical
      schools, and Ontolog, a browser for medical vocabularies.

PMID- 11825194
TI  - Using old technology to implement modern computer-aided decision support for
      primary diabetes care.
AB  - BACKGROUND: Implementation rates of interventions known to be beneficial for
      people with diabetes mellitus are often suboptimal. Computer-aided decision
      support systems (CDSSs) can improve these rates. The complexity of establishing a
      fully integrated electronic medical record that provides decision support,
      however, often prevents their use. OBJECTIVE: To develop a CDSS for diabetes care
      that can be easily introduced into primary care settings and diabetes clinics.
      THE SYSTEM: The CDSS uses fax-machine-based optical character recognition
      software for acquiring patient information. Simple, 1-page paper forms, completed
      by patients or health practitioners, are faxed to a central location. The
      information is interpreted and recorded in a database. This initiates a routine
      that matches the information against a knowledge base so that patient-specific
      recommendations can be generated. These are formatted and faxed back within 4-5
      minutes. IMPLEMENTATION: The system is being introduced into 2 diabetes clinics.
      We are collecting information on frequency of use of the system, as well as
      satisfaction with the information provided. CONCLUSION: Computer-aided decision
      support can be provided in any setting with a fax machine, without the need for
      integrated electronic medical records or computerized data-collection devices.

PMID- 11825196
TI  - Modeling uncertainty in computerized guidelines using fuzzy logic.
AB  - Computerized Clinical Practice Guidelines (CPGs) improve quality of care by
      assisting physicians in their decision making. A number of problems emerges since
      patients with close characteristics are given contradictory recommendations. In
      this article, we propose to use fuzzy logic to model uncertainty due to the use
      of thresholds in CPGs. A fuzzy classification procedure has been developed that
      provides for each message of the CPG, a strength of recommendation that rates the
      appropriateness of the recommendation for the patient under consideration. This
      work is done in the context of a CPG for the diagnosis and the management of
      hypertension, published in 1997 by the French agency ANAES. A population of 82
      patients with mild to moderate hypertension was selected and the results of the
      classification system were compared to whose given by a classical decision tree.
      Observed agreement is 86.6% and the variability of recommendations for patients
      with close characteristics is reduced.

PMID- 11825197
TI  - Challenges in using the Arden Syntax for computer-based nosocomial infection
      surveillance.
AB  - CONTEXT: Detection of outbreaks of infection in the hospital typically requires
      daily manual review of microbiology laboratory test results. This process is time
      consuming, tedious, prone to error and may miss trends in infection. A standard
      formalism for procedural knowledge representation, the Arden Syntax, provides a
      vehicle for implementing algorithms for detecting such infections. OBJECTIVE: To
      design and implement a computer-based system for detection of concerning patterns
      of infection or antibiotic resistance. SETTING: Computer-based event monitor and
      central patient data repository at the Columbia-Presbyterian Medical Center
      (CPMC). RESULTS: We designed a two-phase system, including initial filtering of
      individual patient laboratory results by Arden Syntax Medical Logic Modules
      (MLMs) and subsequent aggregation and analysis across patients and locations
      using a statistical monitor. Preliminary data for the filtration phase
      demonstrate a 94.8% reduction in the volume of messages that must be considered
      in surveillance. CONCLUSIONS: Filtering raw laboratory results using a standard
      formalism eases the process of aggregating data across patients and sites as well
      as detecting trends in infection. There is a need for augmenting such formalisms
      in order to enable population-based decision support.

PMID- 11825198
TI  - A virtual medical record for guideline-based decision support.
AB  - A major obstacle in deploying computer-based clinical guidelines at the point of
      care is the variability of electronic medical records and the consequent need to
      adapt guideline modeling languages, guideline knowledge bases, and execution
      engines to idiosyncratic data models in the deployment environment. This paper
      reports an approach, developed jointly by researchers at Newcastle and Stanford,
      where guideline models are encoded assuming a uniform virtual electronic medical
      record and guideline-specific concept ontologies. For implementing a guideline
      based decision-support system in multiple deployment environments, we created
      mapping knowledge bases to link terms in the concept ontology with the
      terminology used in the deployment systems. Mediation components use these
      mapping knowledge bases to map data in locally deployed medical record
      architectures to the virtual medical record. We discuss the possibility of using
      the HL7 Reference Information Model (RIM) as the basis for a standardized virtual
      medical record, showing how this approach also complies with the European pre
      standard ENV13606 for electronic healthcare record communication.

PMID- 11825199
TI  - Designing and implementing medical web portals: spreading educational and
      research materials on the Internet.
AB  - OBJECTIVES: To design and implement a medical web portal providing access to well
      qualified and high-quality information in the framework of universities and
      hospitals. METHOD: Based on the authors  experience and the published literature,
      a model is proposed which describes the properties of documents in an object
      oriented way. This model clearly separates from usual properties: the subject of
      a document as keywords, and information concerning its type, format, and
      location. RESULTS: An implementation has been done with an existing software that
      allows the capability to organize and index a web site according to the model.
      Experiments have been conducted which demonstrate the feasibility and the utility
      of such an approach. DISCUSSION: The benefits for the users, both designers and
      end users, of using such a portal are discussed. Forthcoming works are described.

PMID- 11825201
TI  - Measuring the success of electronic medical record implementation using
      electronic and survey data.
AB  - Computerization of physician practices is increasing. Stakeholders are demanding
      demonstrated value for their Electronic Medical Record (EMR) implementations. We
      developed survey tools to measure medical office processes, including
      administrative and physician tasks pre- and post-EMR implementation. We included
      variables that were expected to improve with EMR implementation and those that
      were not expected to improve, as controls. We measured the same processes pre
      EMR, at six months and 18 months post-EMR. Time required for most administrative
      tasks decreased within six months of EMR implementation. Staff time spent on
      charting increased with time, in keeping with our anecdotal observations that
      nurses were given more responsibility for charting in many offices. Physician
      time to chart increased initially by 50%, but went down to original levels by 18
      months. However, this may be due to the drop-out of those physicians who had a
      difficult time charting electronically.

PMID- 11825200
TI  - Time trade-off utility modified to accommodate degenerative and life-threatening
      conditions.
AB  - The time trade-off is often argued to be the preferred utility assessment method.
      When measuring current health in its classic form, it involves a comparison of
      two certainties: perfect health and current health, each for a fixed period of
      time and followed by death. This makes the time trade-off insensitive to patient
      fears regarding premature death or worsening health. We suggest the classic time
      trade-off be modified to include subjective rather than actuarial life
      expectancy, and relaxation of the current health option to include uncertainty in
      quantity and quality of life. We illustrate the mechanics of this modified time
      trade-off and report a preliminary application to 122 men presenting to a
      prostate cancer screening program. Further analysis of this modified time trade
      off appears warranted.

PMID- 11825202
TI  - Description of a drug hierarchy in a concept-based reference terminology.
AB  - A concept-based reference terminology that covers all aspects of healthcare is
      essential in developing the Electronic Health Record (EHR). SNOMED Clinical Terms
      (CT), scheduled for release in December 2001, integrates the relative strengths
      of SNOMED RT, and the United Kingdom s Clinical Terms Version 3, formerly known
      as the Read Codes Version 3. It promises to be the most comprehensive terminology
      available. Since a significant portion of the EHR can be drug-related
      information, we describe here some of the background information and rationale
      for the structure and scope of the merged drug hierarchy within SNOMED CT. A
      controlled drug terminology within a reference terminology has the potential to
      support a number of functions within healthcare practice. One of the functions
      proposed is to serve as the bridge between reference terminology and drug
      knowledge bases.

PMID- 11825203
TI  - Automatic MeSH term assignment and quality assessment.
AB  - For computational purposes documents or other objects are most often represented
      by a collection of individual attributes that may be strings or numbers. Such
      attributes are often called features and success in solving a given problem can
      depend critically on the nature of the features selected to represent documents.
      Feature selection has received considerable attention in the machine learning
      literature. In the area of document retrieval we refer to feature selection as
      indexing. Indexing has not traditionally been evaluated by the same methods used
      in machine learning feature selection. Here we show how indexing quality may be
      evaluated in a machine learning setting and apply this methodology to results of
      the Indexing Initiative at the National Library of Medicine.

PMID- 11825204
TI  - Evaluation of the DEFINDER system for fully automatic glossary construction.
AB  - In this paper we present a quantitative and qualitative evaluation of DEFINDER, a
      rule-based system that mines consumer-oriented full text articles in order to
      extract definitions and the terms they define. The quantitative evaluation shows
      that in terms of precision and recall as measured against human performance,
      DEFINDER obtained 87% and 75% respectively, thereby revealing the incompleteness
      of existing resources and the ability of DEFINDER to address these gaps. Our
      basis for comparison is definitions from on-line dictionaries, including the UMLS
      Metathesaurus. Qualitative evaluation shows that the definitions extracted by our
      system are ranked higher in terms of user-centered criteria of usability and
      readability than are definitions from on-line specialized dictionaries. The
      output of DEFINDER can be used to enhance these dictionaries. DEFINDER output is
      being incorporated in a system to clarify technical terms for non-specialist
      users in understandable non-technical language.

PMID- 11825205
TI  - Problems and challenges in patient information retrieval: a descriptive study.
AB  - Many patients now turn to the Web for health care information. However, a lack of
      domain knowledge and unfamiliarity with medical vocabulary and concepts restrict
      their ability to successfully obtain information they seek. The purpose of this
      descriptive study was to identify and classify the problems a patient encounters
      while performing information retrieval tasks on the Web, and the challenges it
      poses to informatics research. In this study, we observed patients performing
      various retrieval tasks, and measured the effectiveness of, satisfaction with,
      and usefulness of the results. Our study showed that patient information
      retrieval often failed to produce successful results due to a variety of
      problems. We propose a classification of patient IR problems based on our
      observations.

PMID- 11825206
TI  - Subjective assessment of usefulness and appropriate presentation mode of alerts
      and reminders in the outpatient setting.
AB  - There is very little known about the limits of alerting in the setting of the
      outpatient Electronic Medical Record (EMR). We are interested in how users value
      and prefer such alerts. One hundred Kaiser Permanente primary care clinicians
      were sent a four-page questionnaire. It contained questions related to the
      usability and usefulness of different approaches to presenting reminder and alert
      information. The survey also contained questions about the desirability of six
      categories of alerts. Forty-three of 100 questionnaires were returned. Users
      generally preferred an active, more intrusive interaction model for "alerts" and
      a passive, less intrusive model for order messages and other types of reminders
      and notifications. Drug related alerts were more highly rated than health
      maintenance or disease state reminders. Users indicated that more alerts would
      make the system "more useful" but "less easy to use".

PMID- 11825208
TI  - Bedside vital signs capture for the non-ICU setting--an open source, PC-based
      solution.
AB  - The efficient and reliable capture of vital signs and other bedside data in the
      non-ICU setting has been a challenging problem for the medical informatics
      community. The problem is compounded by the complexities associated with storage
      of this data into an electronic medical record system (EMRS). There are a lack of
      off-the-shelf solutions that satisfy the basic system requirements of bedside
      data capture, user authentication, data validation prior to storage, error
      handling, and convenience. With the current state of technology available, we
      feel the solution to this problem requires the presence of a PC with custom
      interface software at the bedside. This allows for the successful interface
      between available vital signs capture devices, existing EMRS s, and the user.
      This report summarizes the alternatives we found and our proposed solution to
      this important problem.

PMID- 11825207
TI  - A knowledge model for the interpretation and visualization of NLP-parsed
      discharged summaries.
AB  - At our institution, a Natural Language Processing (NLP) tool called MedLEE is
      used on a daily basis to parse medical texts including complete discharge
      summaries. MedLEE transforms written text into a generic structured format, which
      preserves the richness of the underlying natural language expressions by the use
      of concept modifiers (like change, certainty, degree and status). As a tradeoff,
      extraction of application-specific medical information is difficult without a
      clear understanding of how these modifiers combine. We report on a knowledge
      model for MedLEE modifiers that is helpful for a high level interpretation of NLP
      data and is used for the generation of two distinct views on NLP-parsed discharge
      summaries: A  physician view  offering a condensed overview of the severity of
      patient problems and a  data mining view  featuring binary problem states useful
      for machine learning.

PMID- 11825209
TI  - Large public display boards: a case study of an OR board and design implications.
AB  - A compelling reason for studying artifacts in collaborative work is to inform
      design. We present a case study of a public display board (12 ft by 4 ft) in a
      Level-I trauma center operating room (OR) unit. The board has evolved into a
      sophisticated coordination tool for clinicians and supporting personnel. This
      paper draws on study findings about how the OR board is used and organizes the
      findings into three areas: (1) visual and physical properties of the board that
      are exploited for collaboration, (2) purposes the board was configured to serve,
      and (3) types of physical and perceptual interaction with the board. Findings and
      implications related to layout, size, flexibility, task management, problem
      solving, resourcing, shared awareness, and communication are discussed in an
      effort to propose guidelines to facilitate the design of electronic, computer
      driven display boards in the OR environment.

PMID- 11825210
TI  - A consensus approach to maintain a knowledge based system in pathology.
AB  - The IDEM (Images and Diagnosis from Example in Medicine) software is a
      computerized environment able to store unambiguous descriptions of
      histopathologic images from pathologists. Medical imaging could benefit from such
      environments if they can easily and continuously be maintained. Within the IDEM
      environment, we developed a knowledge management module coupled with a consensus
      module to support knowledge acquisition and maintenance by the experts of the
      domain. Two pathologists, a senior and junior pathologist, reviewed fifty-three
      cases of breast pathology. Our findings indicate 1) that the IDEM knowledge
      management module allows experts to describe images by selecting terms and
      defining new ones if necessary, allowing the construction of a glossary for the
      domain and 2) that the consensus module, developed to store valid multi-experts
      cases, contributes also to validate new terms of the glossary and to refine
      semantic distance between terms. Such methodology could be applied to others
      highly evolving medical domains.

PMID- 11825211
TI  - Acceptability of computerized visual analog scale, time trade-off and standard
      gamble rating methods in patients and the public.
AB  - One technique to enhance patient participation in clinical decision making is
      formal measurement of preferences and values. Three commonly applied methods are
      a visual analog scale(VAS), the standard gamble(SG), and the time trade-off(TTO).
      We studied participants subjective experience using computer implementations
      these methods using scale we call the VIBE (for Value Instrument Battery-
      Evaluation) that measures four aspects of user acceptance (clarity, difficulty,
      reasonableness, and comfort level) Studies were performed in two groups: patients
      with HIV infection (n=75) and a convenience sample of the general public(n=640).
      In the patient study, VIBE scores appeared reliable (Cronbach s alpha of 0.739,
      0.826, and 0.716, for VAS, SG, and TTO ratings, respectively.) Patients 
      acceptance of the VAS the highest, followed by the TTO and the SG method (p<0.05
      for all comparisons). Despite significant enhancements in computer software for
      measuring SG preferences, observed differences in acceptance between SG and VAS
      methods were replicated in the general public study (p<0.0001 for differences).
      The results suggest developers of clinical decision support systems should use
      VAS and TTO rating methods where these methods are theoretically appropriate.

PMID- 11825212
TI  - A system for evaluating inpatient care cost-efficiency in hospital.
AB  - The cost-efficiency evaluation is one important aspect in the health care
      organization performance assessment. This paper introduces the ratio of exact
      cost to Relative Intensity Weights, cost per case weight, as one indicator. A
      statistical approach for cost-efficiency analyses is presented in this paper. The
      analyses would be done at the population level and patient level. The linkage
      between population and individual patients provides the capability to review the
      distributions of several cost-efficiency measures and to do further studies,
      including factor adjustment. A well established health care data warehouse is to
      accomplish a timely and evaluation of the cost-efficiency in hospital.

PMID- 11825213
TI  - PDL: a definition language for trend pattern representation and detection in
      medicine.
AB  - This paper proposes a pattern definition language, PDL, to effectively represent
      and manipulate trend patterns to support medical decision making in time-critical
      domains. Based on a modified version of SDL, a shape definitional language
      introduced by Agrawal, PDL extends the expressive power of SDL in the temporal
      domains. PDL also permits irregular length of elementary patterns to be matched
      in the query. This paper describes the syntax and the semantics of PDL, as well
      as illustrating how it can be applied in a time-critical medical domain.

PMID- 11825214
TI  - The feasibility of remote-controlled assistance as a search tool for patient
      education.
AB  - Patients often desire more information about their conditions than they receive
      during a physician office visit. To address the patient's information needs, a
      touchscreen information kiosk was implemented. Results from the first prototype
      identified interface, security, and technical issues. Misspelling of search terms
      was identified as the most observable cause of search failure. An experimental
      remote control assistance feature was added in the second prototype. The feature
      allowed a medical librarian to provide real-time remote help during searches by
      taking control of the patient's computer. Remote assistance improved patient
      satisfaction, increased ease of use, and raised document retrieval rate (86.7%
      vs. 56.7%). Both patients and librarians found the application useful. Reasons
      included its convenience and flexibility, opportunity for direct patient contact,
      ability to teach through direct demonstration, and complementing the librarian's
      role as an information gateway. The project demonstrated the feasibility of
      applying remote control technology to patient education.

PMID- 11825215
TI  - Empirical treatment of chronic cough--a cost-effectiveness analysis.
AB  - Chronic cough of unknown etiology is often difficult to diagnose, thus, there
      exists controversy regarding the management of such patients. Although the ACCP
      (American College of Chest Physicians) statement in 1998 recommended that
      treatment should follow testing, recent evidence suggests that empirical
      treatment of GERD is more cost-effective than testing followed by treatment, in
      both chronic cough and non-cardiac chest pain. In this paper, we evaluated the
      cost-effectiveness in managing patients with chronic unexplained cough by
      building a decision model, and compared the cost-effectiveness of six most common
      management strategies. The outcome of our analysis demonstrates that empirical
      treatment is the cheapest option, while testing followed by treatment is the most
      expensive option with the shortest time course.

PMID- 11825216
TI  - Standards for the electronic health record, emerging from health care's Tower of
      Babel.
AB  - This paper considers the standardization of an Electronic Health Record (EHR).
      Relations between several distinct medical datasets and information systems are
      mapped in order to derive a more precise definition of the EHR. Two international
      efforts to establish standards for the EHR are presented and critiqued.
      Strategies for standardizing the EHR are analyzed and recommendations are
      provided for approaching the standardization process.

PMID- 11825217
TI  - A study of abbreviations in the UMLS.
AB  - Abbreviations are widely used in medicine. The understanding of abbreviations is
      important for medical language processing and information retrieval systems. The
      Unified Medical Language System (UMLS) contains a large number of abbreviations.
      We hypothesized that extracting and studying the UMLS abbreviations can be
      helpful for understanding the characteristics of abbreviations in medicine. In
      this paper, we describe a method for extracting abbreviations from the UMLS. We
      evaluated the method and studied the ambiguous nature of the abbreviations. In
      addition, the coverage of the UMLS abbreviations in medical reports was studied.
      Using our method, we extracted 163,666 unique (abbreviation, full form) pairs
      from the UMLS with a precision of 97.5%, and a recall of 96%. The UMLS
      abbreviations were highly ambiguous: 33.1% of abbreviations with six characters
      or less had multiple meanings; the average number of different full forms for all
      abbreviations with six characters or less was 2.28. The coverage of the UMLS
      abbreviations in medical reports was over 66%.

PMID- 11825218
TI  - Defining and supporting the diverse information needs of community-based care
      using the web and hand-held devices.
AB  - Community-based healthcare focused on maintaining wellness is becoming
      increasingly prevalent in the United States in an effort to eliminate healthcare
      disparities and reduce healthcare costs. These community-oriented initiatives,
      however, often require partnerships that cross traditional boundaries. As a
      result, these initiatives often lack a common information infrastructure to
      support the care delivery process. We have created and implemented a Web-based
      information and communication system to support the needs of a community-based
      healthcare project for Medicaid beneficiaries in Durham County, North Carolina.
      Through this project, we have identified the relevant information requirements
      and stakeholders for community-based care. In addition, we have explored the use
      of hand-held devices for accessing and collecting clinical information in the
      field. The overall goal of this project is to lower the costs and improve the
      quality of community-based healthcare through improved handling of information.

PMID- 11825219
TI  - IML: An image markup language.
AB  - Image Markup Language is an extensible markup language (XML) schema used to
      describe both image metadata and annotations. It describes both data pertaining
      to an entire image, and data that are tied to specific regions or features of the
      image. Developed for a specific domain in Medical Education, this pa-per
      describes extensions to take advantage of the Dublin Core metadata standard, and
      of an XML schema for vector graphics representation. We have developed a
      prototype system of open source tools implementing an authoring system, a client
      system, and an image annotation database which can be queried though the Web.

PMID- 11825220
TI  - Measuring the quality of medical records: a method for comparing completeness and
      correctness of clinical encounter data.
AB  - This paper explores the attributes of quality in recorded clinical encounter
      data, examines issues in measuring these attributes, and describes a method for
      measuring two attributes, completeness and correctness. The method is defined in
      the context of computer-based records and is demonstrated in a pilot study.
      Videotaped physician-patient encounters and an empiric process of determining a
      gold standard for content are used. The methodology was found to be feasible.
      Problems encountered during the pilot study can be remedied.

PMID- 11825221
TI  - The natural history of the use of healthcare information by women with breast
      cancer: a conceptual model.
AB  - The overall goal of our research agenda is to contribute to improved quality of
      healthcare by identifying factors that foster or inhibit the use of healthcare
      information by patients to make informed healthcare decisions. We propose to
      study the natural history of the use of healthcare information by women with
      breast cancer to support decisions about health care. To do so in this paper we
      propose a conceptual model developed based on an extensive literature review and
      critique that describes patients' health information use over the disease course.
      It will guide our further investigation of the complex relationships among
      patients' personal circumstances, the progress of their medical treatment, and
      their satisfaction and empowerment as informed decision-makers. The model will
      help policy makers and health professionals identify the best means to provide
      patients with useful information, and help all stakeholders in health care
      acquire information needed to improve healthcare quality.

PMID- 11825223
TI  - Re-identification of DNA through an automated linkage process.
AB  - This work demonstrates how seemingly anonymous DNA database entries can be
      related to publicly available health information to uniquely and specifically
      identify the persons who are the subjects of the information even though the DNA
      information contains no accompanying explicit identifiers such as name, address,
      or Social Security number and contains no additional fields of personal
      information. The software program, REID (Re-Identification of DNA), iteratively
      uncovers unique occurrences in visit-disease patterns across data collections
      that reveal inferences about the identities of the patients who are the subject
      of the DNA. Using real-world data, REID established identifiable linkages in 33
      100% of the 10,886 cases explicitly surveyed over 8 gene-based diseases.

PMID- 11825222
TI  - Automating SNOMED coding using medical language understanding: a feasibility
      study.
AB  - This paper evaluates qualitatively the use of the MedLEE natural language
      processing system to code medical narratives directly into the SNOMED
      nomenclature, while retaining the MedLEE information model data structure. A gold
      standard is produced from narrative text manually coded in SNOMED. An automated
      parsing and SNOMED-coding of the narrative text is then automatically generated
      by MedLEE. By comparing MedLEE s output to that of the Gold Standard, the
      capacities of SNOMED and MedLEE to represent the clinical information are
      subsequently evaluated leading to qualitative observations on their respective
      strengths and constraints. In this study, MedLEE did code to SNOMED and captures
      the codes in a sub-structure amenable to interoperability with the description
      logic of SNOMED RT, showing an approach that augments and formalizes SNOMED s
      compositional representation methods to accurately capture information from
      clinical narratives.

PMID- 11825224
TI  - Introducing handheld computing into a residency program: preliminary results from
      qualitative and quantitative inquiry.
AB  - Although published reports describe specific handheld computer applications in
      medical training, we know very little yet about how, and how well, handheld
      computing fits into the spectrum of information resources available for patient
      care and physician training. This paper reports preliminary quantitative and
      qualitative results from an evaluation study designed to track changes in
      computer usage patterns and computer-related attitudes before and after
      introduction of handheld computing. Pre-implementation differences between
      residents  and faculty s usage patterns are interpreted in terms of a "work role"
      construct. We hypothesize that over time residents and faculty will adopt, adapt,
      or abandon handheld computing according to how, and how well, this technology
      supports their successful completion of work role-related tasks. This hypothesis
      will be tested in the second phase of this pre- and post-implementation study.

PMID- 11825225
TI  - "Docs 'n drugs--the virtual polyclinic": an intelligent tutoring system for web
      based and case-oriented training in medicine.
AB  - Since the beginning of the year 2000 medical students of the University of Ulm
      are working in their curriculum with the web-based and case-oriented tutoring
      system "Docs 'n Drugs - The Virtual Polyclinic". The system consists of different
      subsystems and services. One subsystem is the Training System. It is based on
      three models: the Tutoring Process Model, the Case Knowledge Model and the
      Medical Knowledge Model. They describe the tutoring process as a series of nodes
      and steps, depict the structure of the medical cases, and provide the medical
      knowledge respectively. Case knowledge and medical knowledge form the expert
      knowledge of the medical domain. Together with the tutoring process, they build
      the basis for automatic intelligent tutoring. After giving a deeper insight into
      the system architecture and the training case structure, an informal evaluation
      shows a first feedback of the learners.

PMID- 11825226
TI  - Foundational model of neuroanatomy: implications for the Human Brain Project.
AB  - In order to meet the need for a controlled terminology in neuroinformatics, we
      have integrated the extensive terminology of NeuroNames into the Foundational
      Model of anatomy. We illustrate the application of foundational principles for
      the establishment of an inheritance hierarchy, which accommodates anatomical
      attributes of neuroanatomical concepts and provides the foundation to which other
      information may be linked.

PMID- 11825227
TI  - Evaluation of a filmless radiology pilot--a preliminary report.
AB  - The development of the Multimedia Electronic Medical Record System (MEMRS)
      promises new opportunities to significantly reduce the routine use of film as the
      medium for viewing radiological medical images. The effect of this change to
      digital media on physician workflow and the perceived value and utility of
      medical images is an area of ongoing investigation. In this study we examined
      oncology clinicians  use of medical images in a MEMRS. We conducted observational
      studies of clinicians during a filmless radiology pilot study in which a filmless
      environment was simulated but the actual film was available on request. This
      observational study was the first step in a comprehensive evaluation designed to
      elucidate the issues surrounding the implementation of a filmless radiology
      environment. We identified and examined several of these issues, including
      physician concern regarding the utility of digital images for clinical use and
      comparison with film, the need to address the effects of image compression with
      clinicians, and the workflow changes necessary to incorporate digital image use
      into a clinical practice.

PMID- 11825228
TI  - Evaluating UMLS strings for natural language processing.
AB  - The National Library of Medicine's Unified Medical Language System (UMLS) is a
      rich source of knowledge in the biomedical domain. The UMLS is used for research
      and development in a range of different applications, including natural language
      processing (NLP). In this paper we investigate the nature of the strings found in
      the UMLS Metathesaurus and evaluate them for their usefulness in NLP. We begin by
      identifying a number of properties that might allow us to predict the likelihood
      of a given string being found or not found in a corpus. We use a statistical
      model to test these predictors against our corpus, which is derived from the
      MEDLINE database. For one set of properties the model correctly predicted 77% of
      the strings that do not belong to the corpus, and 85% of the strings that do
      belong to the corpus. For another set of properties the model correctly predicted
      96% of the strings that do not belong to the corpus and 29% of the strings that
      do belong to the corpus.

PMID- 11825229
TI  - Perceived information needs and communication difficulties of inpatient
      physicians and nurses.
AB  - In order to understand the differing perceptions of information needs and
      communication patterns of healthcare professionals as they relate to medical
      errors, we conducted a survey and 5 focus group sessions of inpatient physicians
      and nurses. Although nurses and physicians stated differing information needs,
      both groups expressed significant problems with obtaining patient, domain and
      institution-specific information in a timely manner. Identification of
      appropriate providers and establishing contact with those people was perceived as
      the most pressing communication need. All focus group participants felt that
      communication difficulties were common and could give examples in which such
      difficulties led to adverse events. Our studies suggest that information needs
      and communication difficulties are common and can lead to medical errors or near
      misses. Many of these problems may be amenable to information technology
      solutions.

PMID- 11825231
TI  - The role of definitions in biomedical concept representation.
AB  - The Foundational Model (FM) of anatomy, developed as an anatomical enhancement of
      UMLS, classifies anatomical entities in a structural context. Explicit
      definitions have played a critical role in the establishment of FM classes.
      Essential structural properties that distinguish a group of anatomical entities
      serve as the differentiate for defining classes. These, as well as other
      structural attributes, are introduced as template slots in Protege, a frame-based
      knowledge acquisition system, and are inherited by descendants of the class. A
      set of desiderata has evolved during the instantiation of the FM for formulating
      definitions. We contend that 1. these desiderata generalize to non-anatomical
      domains and 2. satisfying them in constituent vocabularies of UMLS would enhance
      the quality of information retrievable through UMLS.

PMID- 11825230
TI  - Using narrative reports to support a digital library.
AB  - The vast amount of information collected and stored in clinical systems can be a
      significant challenge in the integration of digital libraries and electronic
      medical records, especially the selection of clinical data to be used in the
      search, retrieval, and summarization processes. In this study, we describe the
      use of information retrieval measures with natural language processor output to
      identify critical information in narrative reports. Our hypothesis is that
      clinical data that occur often in narrative reports are less important to
      clinicians than findings that occur rarely. We used the information retrieval
      methods to analyze one year of discharge summaries. We then conducted a
      performance study, using physicians as subject. Results show that the methods can
      be used for filtering critical information from reports. Further studies need to
      be done on evaluation of the method based on an evaluation of the system
      performance in the context of a digital library.

PMID- 11825232
TI  - Disease specific intelligent pre-fetch and hanging protocol for diagnostic
      neuroradiology workstations.
AB  - Clinical data sets for neuroradiological cases can be quite large. A typical
      brain tumor patient at UCLA will undergo 8-10 separate studies over a 2 year
      period, each study will produce 60-100 magnetic resonance (MR) images. Gathering
      and sorting through a patient s imaging events during the course of treatment can
      be both overwhelming and time consuming. The purpose of this research is to
      develop an intelligent pre-fetch and hanging protocol that automatically gathers
      the relevant prior examinations from a picture archiving, and communication
      systems (PACS) archive and sends the pertinent historical images to the
      diagnostic display station where the new examination is subsequently read out.
      The intelligent hanging protocol describes the type of layout and sequence for
      image display. We have developed a classification scheme to organize the
      pertinent patient information to selectively pre-fetch and intelligently present
      the images to review brain tumor cases for a diagnostic neuroradiology
      workstation.

PMID- 11825233
TI  - A model for data integration systems of biomedical data applied to online genetic
      databases.
AB  - We present a general model for data integration systems using a mediated schema
      to represent commonalities in the underlying sources. These sources are mapped to
      the mediated schema using source descriptions. Users can pose queries against the
      mediated schema, allowing the system to generate automatically a query plan that
      enumerates and ranks all possible ways in which the query could be answered. We
      apply this approach to the domain of online genetic databases, demonstrating the
      system s ability to answer relevant queries across multiple sources.

PMID- 11825234
TI  - The operating room charge nurse: coordinator and communicator.
AB  - To achieve the potential inherent in the use of computer applications in
      distributed environments, we need to understand the information needs of users.
      The purpose of this descriptive study was to document the communication of an
      operating room charge nurse to inform the design of technological communication
      applications for operating room coordination. A data collection tool was
      developed to record: 1) the purpose of the communication, 2) mode of
      communication, 3) the target individual, and 4) the length of time taken for each
      occurrence. The chosen data collection categories provided a functional structure
      for data collection and analysis involving communication. Study findings are
      discussed within the context of application design.

PMID- 11825235
TI  - Easing the transition between attribute-value databases and conventional
      databases for scientific data.
AB  - We have previously developed and described a modeling and development framework
      called EAV/CR, which is appropriate for designing databases containing highly
      heterogeneous and evolving data, as in the case of scientific databases for
      rapidly advancing domains. The use of EAV/CR has been hampered by the lack of
      generic tools for non-procedurally transferring data into or out of legacy
      systems or analytical packages: the transfer task is complicated by the different
      representation of EAV vs. conventional data, which is not addressed by commercial
      data-transfer programs. We have therefore created such a tool, which works with a
      wide variety of data sources that are accessible via Microsoft OLE DB technology.
      The data transfer tool requires minimal programmer intervention to set up, and no
      programming to use on a regular basis. Current limitations of the tool are also
      noted.

PMID- 11825236
TI  - ECG Wave-Maven: a self-assessment program for students and clinicians.
AB  - Proficiency in the interpretation of electrocardiograms (ECGs) is an essential
      skill for medical students, house officers, and attending physicians. However,
      resources to develop and upgrade the necessary high level of "ECG literacy" are
      limited. A small number of centers have attempted to address this challenge by
      developing "ECG of the week" internet sites. These resources are difficult to
      maintain and update, and many of them quickly become stagnant. We present "ECG
      Wave-Maven," an innovative web-based tutorial that overcomes these obstacles via
      a direct link to the hospital's extensive and increasing clinical ECG repository.
      By interfacing our educational tool to live data, we can greatly decrease the
      time and effort required from the time a practitioner notes an interesting case
      to its inclusion in the program. Users can opt to encounter the test cases
      sequentially or randomly, or by reviewing a list of questions or diagnoses,
      making this not just a quiz, but a basic educational reference. This tool may be
      useful in meeting the challenge of reducing serious medical errors related to ECG
      misinterpretation.

PMID- 11825238
TI  - Closing the loop in ICU decision support: physiologic event detection, alerts,
      and documentation.
AB  - Automated physiologic event detection and alerting is a challenging task in the
      ICU. Ideally care providers should be alerted only when events are clinically
      significant and there is opportunity for corrective action. However, the concepts
      of clinical significance and opportunity are difficult to define in automated
      systems, and effectiveness of alerting algorithms is difficult to measure. This
      paper describes recent efforts on the Simon project to capture information from
      ICU care providers about patient state and therapy in response to alerts, in
      order to assess the value of event definitions and progressively refine alerting
      algorithms. Event definitions for intracranial pressure and cerebral perfusion
      pressure were studied by implementing a reliable system to automatically deliver
      alerts to clinical users  alphanumeric pagers, and to capture associated
      documentation about patient state and therapy when the alerts occurred. During a
      6-month test period in the trauma ICU at Vanderbilt University Medical Center,
      530 alerts were detected in 2280 hours of data spanning 14 patients. Clinical
      users electronically documented 81% of these alerts as they occurred.
      Retrospectively classifying documentation based on therapeutic actions taken, or
      reasons why actions were not taken, provided useful information about ways to
      potentially improve event definitions and enhance system utility.

PMID- 11825237
TI  - Developing a taxonomy for research in adverse drug events: potholes and
      signposts.
AB  - Computerized decision support and order entry shows great promise for reducing
      adverse drug events (ADEs). The evaluation of these solutions depends on a
      framework of definitions and classifications that is clear and practical.
      Unfortunately the literature does not always provide a clear path to defining and
      classifying adverse drug events. While not a systematic review, this paper uses
      examples from the literature to illustrate problems that investigators will
      confront as they develop a conceptual framework for their research. It also
      proposes a targeted taxonomy that can facilitate a clear and consistent approach
      to the research of ADEs and aid in the comparison to results of past and future
      studies. The taxonomy addresses the definition of ADE, types, seriousness, error,
      and causality.

PMID- 11825239
TI  - Effects of data anonymization by cell suppression on descriptive statistics and
      predictive modeling performance.
AB  - Protecting individual data in disclosed databases is essential. Data
      anonymization strategies can produce table ambiguation by suppression of selected
      cells. Using table ambiguation, different degrees of anonymization can be
      achieved, depending on the number of individuals that a particular case must
      become indistinguishable from. This number defines the level of anonymization.
      Anonymization by cell suppression does not necessarily prevent inferences from
      being made from the disclosed data. Preventing inferences may be important to
      preserve confidentiality. We show that anonymized data sets can preserve
      descriptive characteristics of the data, but might also be used for making
      inferences on particular individuals, which is a feature that may not be
      desirable. The degradation of predictive performance is directly proportional to
      the degree of anonymity. As an example, we report the effect of anonymization on
      the predictive performance of a model constructed to estimate the probability of
      disease given clinical findings.

PMID- 11825241
TI  - Integration of radiographic images with an electronic medical record.
AB  - Radiographic images are important and expensive diagnostic tests. However, the
      provider caring for the patient often does not review the images directly due to
      time constraints. Institutions can use picture archiving and communications
      systems to make images more available to the provider, but this may not be the
      best solution. We integrated radiographic image review into the Regenstrief
      Medical Record System in order to address this problem. To achieve adequate
      performance, we store JPEG compressed images directly in the RMRS. Currently,
      physicians review about 5% of all radiographic studies using the RMRS image
      review function.

PMID- 11825240
TI  - The role of clinical informatics in the Agency for Healthcare Research and
      Quality's efforts to improve patient safety.
AB  - In 1998, the Institute of Medicine (IOM) issued a report on medical errors, which
      estimated that up to 98,000 people die in U.S. hospitals each year from errors.
      This report raised concerns that medical errors have become a national public
      health problem that should be addressed in the same manner as other epidemics
      such as heart disease, diabetes, and obesity. In 2001, the IOM released a follow
      up report encompassing a broader range of quality issues. They concluded that the
      U.S. healthcare system is outmoded and incapable of providing consistent, high
      quality care. They outlined a strategy for redesigning U.S. healthcare delivery
      to achieve safe, dependable, high-quality care, which emphasizes information
      technology as an integral part of the solution. AHRQ's fiscal year 2001
      appropriation included an increase of $50 million dollars for initiatives to
      reduce medical errors and improve patient safety. AHRQ responded to this mandate
      by developing a series of research solicitations that form an integrated set of
      activities to design and test best practices for reducing errors in multiple
      health care settings. This paper discusses the components of this program and the
      central role of medical informatics research in the Agency's efforts to improve
      the safety of medical care in America.

PMID- 11825242
TI  - PathworX: an informatics tool for quality improvement.
AB  - To optimize quality of care while conserving resources requires the right
      information and the right organizational processes. PathworX, a care management
      and documentation system developed at Vanderbilt, coordinates interdisciplinary
      care based on evidence-based best practices and provides information about the
      achievement of patient care goals as an indicator of quality. Using data about
      goal achievement and resource consumption in a process of continual quality
      improvement enables hospital units to reduce waste while improving patient
      outcomes.

PMID- 11825244
TI  - Attitudes of academic-based and community-based physicians regarding EMR use
      during outpatient encounters.
AB  - Physician satisfaction with EMR implementations has been reported in a number of
      recent studies. Most of these have reported on implementation of an EMR in a
      uniform practice setting rather than comparing satisfaction with implementation
      between settings. Our objectives in this study were to: 1) compare and contrast
      the attitudes of academic-based and community-based primary care physicians
      toward EMR use 6 months after implementation, and 2) investigate some of the
      factors influencing their attitudes toward the EMR implementation. Although
      physicians in both settings regularly use computers, the academic-based
      physicians use computers for a wider range of activities. Both groups endorse
      improvements in quality and communication as well as concern over rapport with
      the patient and privacy. There is considerable discrepancy between the two
      settings in ratings of the impact on workflow, with the community-based
      physicians being much more positive about the EMR. Factors that may account for
      this discrepancy may include overall expectations of computer systems as well as
      different rates of adaptation to use of the system.

PMID- 11825243
TI  - Using features of Arden Syntax with object-oriented medical data models for
      guideline modeling.
AB  - Computer-interpretable guidelines (CIGs) can deliver patient-specific decision
      support at the point of care. CIGs base their recommendations on eligibility and
      decision criteria that relate medical concepts to patient data. CIG models use
      expression languages for specifying these criteria, and define models for medical
      data to which the expressions can refer. In developing version 3 of the GuideLine
      Interchange Format (GLIF3), we used existing standards as the medical data model
      and expression language. We investigated the object-oriented HL7 Reference
      Information Model (RIM) as a default data model. We developed an expression
      language, called GEL, based on Arden Syntax's logic grammar. Together with other
      GLIF constructs, GEL reconciles incompatibilities between the data models of
      Arden Syntax and the HL7 RIM. These incompatibilities include Arden's lack of
      support for complex data types and time intervals, and the mismatch between
      Arden's single primary time and multiple time attributes of the HL7 RIM.

PMID- 11825245
TI  - Narrative notes in a nursing information system (NIS).
AB  - Today s rapidly changing health care environment creates pressure for the
      computerization of the patient record. Two requirements for inclusion of nursing
      activities into the computerized patient record (CPR) are a standardized nursing
      language of sufficient granularity and a database that allows for one time
      collection of data for multiple uses. Documentation systems raise issues of data
      completeness. Using a descriptive methodology, nursing documentation in one CPR
      was examined for prevalence and content of free text documentation in an
      otherwise structured nursing information system (NIS). Results demonstrate house
      wide use of free text (narrative note) fields. Variability in use unrelated to
      patient acuity suggests idiosyncratic individual or unit documentation practices.
      Findings support the use of quality management activities to improve
      documentation practices and point to areas of database enhancement and
      information system development.

PMID- 11825246
TI  - An electronic documentation system increases diagnostic code capture for very low
      birth weight infants.
AB  - INTRODUCTION: Information describing medical interventions and patient outcome of
      very low birth weight (VLBW; BW <1500 grams) infants who receive neonatal
      intensive care is necessary to evaluate the quality of health care. We developed
      an electronic patient documentation system (EDS) called PCode to identify and
      select patient diagnostic (DX) codes and compared EDS to the previous paper-based
      documentation system (PDS). Our hypothesis was that EDS would capture more
      patient diagnostic codes than PDS. METHODS: PDS was originally developed as a two
      page 'code sheet' which listed all 275 neonatal diagnoses/management options and
      corresponding 3-4 character diagnostic (DX) codes, organized by organ system. PDS
      code sheets were manually completed by one of three trained 'coders' for every
      neonatal patient. EDS was developed as a Java application with the 'coder'
      selecting DX codes from drop lists also categorized by organ system. The study
      intervention was patient code selection using either the PDS or the EDS system.
      Both systems produced a paper DX code summary. PDS data capture occurred from
      11/1997-3/1999 followed by EDS data capture until 8/2000. The primary outcome
      variable was DX codes captured per patient. Data were analyzed using independent
      t-test and linear regression. RESULTS: The number of diagnoses increased with
      decreasing birth weight. After linear regression was applied to control for birth
      weight, the number of DX codes was 31% greater in the EDS group, 7.2 +/- 2.9 DX
      codes/patient, p=0.008. There was a trend towards fewer erroneous DX codes in the
      EDS group. The most common DX codes were hyaline membrane disease, sepsis
      evaluation and hyperbilirubinemia, as expected for this patient population.
      CONCLUSIONS: EDS captured more VLBW infant DX codes compared to PDS. These
      results support the transition toward electronic data documentation for the
      neonatal clinical environment. Electronically linking PCode to the patient
      database has been initiated and should reduce manual coding errors.

PMID- 11825247
TI  - Patients as experts: a collaborative performance support system.
AB  - Performance support systems that provide decision support and encourage quality
      improvement historically focus on physicians as the expert to the exclusion of an
      active role for patients. This paper outlines an argument for the development of
      a collaborative expert system in the acute care setting that emphasizes a key
      role for patients. Patients are not just seekers of information; they remain
      capable of sharing and integrating their knowledge and expertise actively in an
      electronically-supported care process. Collaborative use of information
      technology emerges as a novel variation of consumer informatics. I will define
      specific domains of expertise for patients and place the proposed collaborative
      expert system within the framework of Wagner's view of idealized collaborative
      care for chronic illness. Basic architecture for a patient-inclusive system is
      proposed with additional detail provided for a patient-level interface targeting
      pediatric asthma. The benefits of the electronically-supported collaboration
      include the activation of patients in the information-sharing process, enhanced
      decision support, a patient-focused needs assessment, and improved communication
      and partnership between patients and providers.

PMID- 11825248
TI  - Server-based approach to web visualization of integrated 3-D medical image data.
AB  - Although computer processing power and network bandwidth are rapidly increasing,
      the average desktop is still not able to rapidly process large datasets such as 3
      D medical image volumes. We have therefore developed a server side approach to
      this problem, in which a high performance graphics server accepts commands from
      web clients to load, process and render 3-D image volumes and models. The
      renderings are saved as 2-D snapshots on the server, where they are uploaded and
      displayed on the client. User interactions with the graphic interface on the
      client side are translated into additional commands to manipulate the 3-D scene,
      after which the server re-renders the scene and sends a new image to the client.
      Example forms-based and Java-based clients are described for a brain mapping
      application, but the techniques should be applicable to multiple domains where 3
      D medical image visualization is of interest.

PMID- 11825249
TI  - Patients following their echoes: the effect of telemedicine on institutional
      referral patterns.
AB  - Increasing market share by attracting patient referrals has long been cited as a
      justification for implementing telemedicine. METHODS: At the onset of this study,
      there were two level III NICUs in North Carolina that did not have on-site
      cardiology support. During the study period, both institutions set up
      telemedicine links to the University of North Carolina Health Care System for the
      provision of rapid cardiology support. OBJECTIVE: This paper tests the hypothesis
      that telemedicine was associated with an increase in the percentage of newborn
      referrals transferred to UNC instead of the other academic medical centers.
      RESULTS: Analysis of a total of 201 transfers over a three and a half year period
      shows that the percentage of acute transfers to UNC increased from 58 % during
      the pre-intervention phase to 86 % in the post-intervention phase (p = 0.001). An
      increase in transfers to UNC was observed from both of the level III centers.
      CONCLUSION: Telemedicine was an effective tool to attract patient referrals in a
      competitive tertiary care environment.

PMID- 11825250
TI  - A web-based tool to retrieve human genome polymorphisms from public databases.
AB  - Single Nucleotide Polymorphisms (SNPs) are the most important source of variation
      in our genome, and an invaluable tool in the hands of researchers who investigate
      genetic diseases. Databases of SNPs are growing at a very fast rate, and the
      ability to perform large-scale, high-resolution association studies is quickly
      becoming a reality. In this paper we describe SNPper, a web-based tool to search
      for SNPs in public databases. The system allows searching for all SNPs in a given
      set of genes (for candidate gene studies) or in a specified region of a
      chromosome. The information displayed for each gene or each SNP is fully
      annotated and linked to the leading bioinformatics web sites. The first release
      of SNPper is available on the web, and has received positive feedback from the
      genetic and bioinformatics community.

PMID- 11825251
TI  - Empirical data for the semantic interpretation of prepositional phrases in
      medical documents.
AB  - We report on the results from an empirical study deal-ing with the semantic
      interpretation of prepositional phrases in medical free texts. We use a small
      number of semantic interpretation schemata only, which operate on well-defined
      configurations in dependency graphs. We provide a quantitative analysis of the
      performance of the semantic interpreter in terms of recall/precision data, and
      consider, in qualitative terms, the impact semantic interpretation patterns have
      on the construction of the underlying medical ontology.

PMID- 11825252
TI  - Expression of a domain ontology model in unified modeling language for the World
      Health Organization International classification of impairment, disability, and
      handicap, version 2.
AB  - The International Classification of Impairment, Disability, and Handicap Version
      2(ICIDH-2), an anticipated addition to the World Health Organization suite of
      terminologies, has been put forth as a means for standardized representation of
      generic health and/or functional status data. In an attempt to make explicit the
      ontology upon which ICIDH-2 is based the authors derived a concept model
      expressed as a Unified Modeling Language static class diagram through abstraction
      of concept-terms in the documentation provided with the Full Version Pre-Final
      Draft of ICIDH-2 (December 2000). ICIDH-2's semantic structure is analyzed and
      evaluated for its semantic consistency. Discussion is presented on the utility of
      domain ontology models in terminology development and potential roles ICIDH-2
      might play, as it undergoes refinement towards a representational standard. It is
      intended that the proposed UML rendering will stimulate domain discourse and
      consensus that will lead to enhancement of conceptual clarity in the ICIDH-2
      ontological hierarchy and further enable its study and development as a
      healthcare classification.

PMID- 11825253
TI  - Culling a clinical terminology: a systematic approach to identifying problematic
      content.
AB  - The College of American Pathologists and the National Health Service (NHS) in the
      United Kingdom are merging their respective clinical terminologies, SNOMED RT and
      Clinical Terms Version 3, into a new terminology, SNOMED CT. This requires
      mapping concept descriptions between the two existing terminologies. During the
      mapping process, many descriptions were identified as being potentially
      problematic. They require further review by the SNOMED editorial process before
      either (1) being incorporated into SNOMED CT, or (2) retired from active use.
      This article presents data on the concept descriptions that were identified as
      needing further review during the early phases of SNOMED CT development. Based on
      this work, we describe fourteen types of problematic terminology content.
      Identifying problematic terminology content can be approached in a systematic
      manner.

PMID- 11825255
TI  - Fuzzy K-means clustering with missing values.
AB  - Fuzzy K-means clustering algorithm is a popular approach for exploring the
      structure of a set of patterns, especially when the clusters are overlapping or
      fuzzy. However, the fuzzy K-means clustering algorithm cannot be applied when the
      real-life data contain missing values. In many cases, the number of patterns with
      missing values is so large that if these patterns are removed, then sufficient
      number of patterns is not available to characterize the data set. This paper
      proposes a technique to exploit the information provided by the patterns with the
      missing values so that the clustering results are enhanced. There are various
      preprocessing methods to substitute the missing values before clustering the
      data. However, instead of repairing the data set at the beginning, the repairing
      can be carried out incrementally in each iteration based on the context. In that
      case, it is more likely that less uncertainty is added while incorporating the
      repair work. This scheme is further consolidated in this paper by fine-tuning the
      missing values using the information from other attributes. The applications of
      the proposed method in medical domain have produced good performance.

PMID- 11825254
TI  - The effects on clinician ordering patterns of a computerized decision support
      system for neuroradiology imaging studies.
AB  - OBJECTIVE: To evaluate the impact of computerized ordering guidelines on
      clinician ordering patterns for neuroradiology imaging studies of the head.
      DESIGN: A retrospective analysis was performed using a pre-post design. A 9-week
      control period was followed by an 8-week intervention period. SUBJECTS: All
      clinicians who placed an order for either an MRI of the brain or a CT of the head
      on inpatients using a computerized order entry system. METHODS: We designed,
      implemented, and evaluated a decision support system for the implementation of
      test ordering guidelines. Changes in ordering patterns were evaluated with a Chi
      square analysis. RESULTS: 742 tests were ordered in the pre-intervention period,
      while 704 studies were ordered after the intervention. A significant change in
      the distribution of tests ordered resulted from the intervention (p=0.048).
      Changes trended toward the guideline recommendations for all tests considered.
      60% of users receiving a recommendation ordered the suggested study. DISCUSSION:
      Our intervention successfully influenced clinician ordering patterns. Examination
      of detailed usage patterns may aid in further quality improvement of both the
      guidelines and the decision support tool used to implement them.

PMID- 11825256
TI  - Representing and querying conceptual graphs with relational database management
      systems is possible.
AB  - This is an experimental study on the feasibility of maintaining medical concept
      dictionaries in production grade relational database management systems (RDBMS.)
      In the past, RDBMS did not support transitive relational structures and had
      therefore been unsuitable for managing knowledge bases. The revised SQL-99
      standard, however, may change this. In this paper we show that modern RDBMS that
      support recursive queries are capable of querying transitive relationships in a
      generic data model. We show a simple but efficient indexed representation of
      transitive closure. We could confirm that even challenging combined transitive
      relationships can be queried in SQL.

PMID- 11825257
TI  - Developing a protocol for an educational software competition.
AB  - This project developed a protocol for the inaugural Instructional Software
      Competition of the American Dental Education Association (ADEA). The evaluation
      instrument was derived from the Guidelines for the Design of Educational Software
      developed by the ANSI-accredited Standards Committee for Dental Informatics.
      Eleven judges were calibrated in a conference call and rated a total of 30
      submissions using a 66-question instrument. The maximum score was 204 points. The
      mean score of WWW-based programs was 106.7 points, and of CD-ROM-based programs
      109.5 points. The summative review of the judging process identified several
      potential improvements, such as distinguishing between standalone programs and
      educational support material; increasing the number of answer choices on rating
      scales; differential weighting of criteria; and a more discriminative approach to
      judging formative and summative evaluations. We plan to improve the protocol by
      supporting the process through a Web-based application; calibrating judges with
      an online handbook; improving and adapting the rating instrument itself; using at
      least three judges for each program; and conducting a measurement study.

PMID- 11825258
TI  - Bidirectional mereological reasoning in anatomical knowledge bases.
AB  - Mereological relationships--relationships between parts and wholes--are essential
      for ontological engineering in the anatomical domain. We propose a knowledge
      engineering approach that emulates mereological reasoning by taxonomic reasoning
      based on SEP triplets, a special data structure for the encoding of part-whole
      relations, which is fully embedded in the formal framework of standard
      description logics. We extend the SEP formalism in order to account not only for
      the part-of but also for the has-part relation, both being considered transitive
      in our domain. Furthermore we analyze the distinction between the ontological
      primitives singletons, collections and mass concepts in the anatomy domain and
      sketch how reasoning about these kinds of concepts can be accounted for in a
      knowledge representation language, using the extended SEP formalism.

PMID- 11825259
TI  - Evaluation of clinician response to wireless technology.
AB  - The purpose of this study was to investigate the safety, use and response of
      clinical staff to wireless technology. A convenience sample of clinical staff was
      surveyed using a variety of assessment tools. The environmental assessment
      determined there was no interference between the wireless devices and the
      biomedical equipment on the patient care units. Survey results indicated a high
      level of acceptance for the wireless technology related to perceived usefulness,
      perceived ease of use, impact, adoption, advantage and future need. Results
      indicated a strong, significant relationship between adoption and perceived
      usefulness (r(s)=.71 p<.01; r(2)(s)=.50).

PMID- 11825260
TI  - Integration of textual guideline documents with formal guideline knowledge bases.
AB  - Numerous approaches have been proposed to integrate the text of guideline
      documents with guideline-based care systems. Current approaches range from
      serving marked up guideline text documents to generating advisories using complex
      guideline knowledge bases. These approaches have integration problems mainly
      because they tend to rigidly link the knowledge base with text. We are developing
      a bridge approach that uses an information retrieval technology. The new approach
      facilitates a versatile decision-support system by using flexible links between
      the formal structures of the knowledge base and the natural language style of the
      guideline text.

PMID- 11825261
TI  - Normal forms for description logic expressions of clinical concepts in SNOMED RT.
AB  - Modern clinical terminologies organize concepts into multi-hierarchy structures
      that are defined by logic-based expressions, enabling compositional
      representation of clinical statements and supporting more complete and consistent
      retrieval of clinical data. The Systematized Nomenclature of Medicine, Reference
      Terminology (SNOMED RT) gives each concept code a semantic definition stated in
      description logic. The process of development, testing and distribution of these
      definitions has highlighted the fact that a concept definition may take many
      different but logically equivalent forms, and has revealed a need for a set of
      normal forms for authoring, distribution, and other purposes. This paper
      describes the difference between a choice of syntax and a choice of normal form,
      and defines several different normal forms, including a short canonical form, a
      long canonical form, and a distribution normal form.

PMID- 11825262
TI  - PDA support for outpatient clinical clerkships: mobile computing for medical
      education.
AB  - This project provides educational support for students enrolled in a family
      practice clerkship by supplying PDA-based clinical references and tools to
      collect information about the patients they see and the seminars they attend.
      Each student is supplied with a Handspring Visor Deluxe to use during the
      clerkship. Supplied software includes a clinical reference (Five Minute Clinical
      Consult) and Lexidrugs drug reference and a medical calculator. The data
      collection software consists of a patient log for recording simple demographic
      and diagnostic information about each patient seen during the clerkship, a
      seminar evaluation module for recording student feedback about each didactic
      presentation during the course, and an evaluation form where they students supply
      their reactions to the use of the Visor. Despite encountering a number of
      problems, the devices appear to be beneficial tools. The applications provide
      useful references for students who do not have access to the resources of the
      University in their family medicine clerkship. They also provide an improved,
      though not perfect, means to capture data regarding patient encounters and course
      evaluations. However, the challenge remains to better integrate the PDA with the
      student s workflow in the clinic.

PMID- 11825263
TI  - HPARSER: extracting formal patient data from free text history and physical
      reports using natural language processing software.
AB  - A prototype, HPARSER, processes a patient history and physical report such that
      specific data are obtained and stored in a patient data record. HPARSER is a
      recursive transition network (RTN) parser, and includes English and medical
      grammar rules, lexicon, and database constraints. Medical grammar rules augment
      the grammar rule base and specify common phrases seen in patient reports (e.g.,
      "pupils are equal and reactive"). Each database constraint associates a grammar
      rule with a database table and attribute. Constraint behavior is such that if a
      rule is satisfied, data is extracted from the parse tree and stored into the
      database. Control reports guided construction of grammar and constraint rules.
      Test reports were processed with the control rules. 85% of test report sentences
      parsed and a 60% data capture rate, compared to controls, was achieved. HPARSER
      demonstrates use of an RTN to parse patient reports, and database constraints to
      transfer formal data from parse trees into a database.

PMID- 11825264
TI  - MeSHmap: a text mining tool for MEDLINE.
AB  - Our research goal is to explore text mining from the metadata included in MEDLINE
      documents. We present MeSHmap our prototype text mining system that exploits the
      MeSH indexing accompanying MEDLINE records. MeSHmap supports searches via PubMed
      followed by user driven exploration of the MeSH terms and subheadings in the
      retrieved set. The potential of the system goes beyond text retrieval. It may
      also be used to compare entities of the same type such as pairs of drugs or pairs
      of procedures etc. In addition there is the potential to generate maps of
      entities (drugs or diseases etc.) such that the strength of the link between two
      entities in the map represents their similarity as expressed in the MeSH metadata
      of the MEDLINE documents. Higher level operators have been proposed to support
      these comparison and mapping functions. This paper motivates and describes
      MeSHmap. Future work will include user evaluations of the system.

PMID- 11825265
TI  - Towards health care process description framework: an XML DTD design.
AB  - The development of health care and hospital information systems has to meet users
      needs as well as requirements such as the tracking of all care activities and
      the support of quality improvement. The use of process-oriented analysis is of
      value to provide analysts with: (i) a systematic description of activities; (ii)
      the elicitation of the useful data to perform and record care tasks; (iii) the
      selection of relevant decision-making support. But paper-based tools are not a
      very suitable way to manage and share the documentation produced during this
      step. The purpose of this work is to propose a method to implement the results of
      process analysis according to XML techniques (eXtensible Markup Language). It is
      based on the IDEF0 activity modeling language (Integration DEfinition for
      Function modeling). A hierarchical description of a process and its components
      has been defined through a flat XML file with a grammar of proper metadata tags.
      Perspectives of this method are discussed.

PMID- 11825266
TI  - Using a web-based prototype and human-computer interaction concepts to develop a
      vision for a next generation patient care management system.
AB  - This paper describes the novel use of two tools to develop requirements for a new
      generation patient care system: a web-based prototype and a human-computer
      interaction framework. These tools allowed a development team to crystallize new
      requirements for a patient care system, illustrate to clinicians a radical change
      in care process models, and begin the change management process in a large
      enterprise.

PMID- 11825267
TI  - Making grandma's data secure: a security architecture for home telemedicine.
AB  - Home telemedicine presents special challenges for data security and privacy.
      Experience in the Informatics for Diabetes Education And Telemedicine (IDEATel)
      project has demonstrated that data security is not a one-size-fits-all problem.
      The IDEATel users include elderly patients in their homes, nurse case managers,
      physicians, and researchers. The project supports multiple computer systems that
      require a variety of user interactions, including: data entry, data review,
      patient education, videoconferencing, and electronic monitoring. To meet these
      various needs, a number of different of security solutions were utilized,
      including: UserID/Password, PKI certificates, time-based tokens, IP filtering,
      VPNs, symmetric and asymmetric encryption schemes, firewalls and dedicated
      connections. These were combined in different ways to meet the needs of each user
      groups.

PMID- 11825268
TI  - SNOMED clinical terms: overview of the development process and project status.
AB  - Two large health care reference terminologies, SNOMED RT and Clinical Terms
      Version 3 , are in the process of being merged to form a comprehensive new work
      referred to as SNOMED Clinical Terms. The College of American Pathologists and
      the United Kingdom s National Health Service have entered into a collaborative
      agreement to develop this new work. Both organizations have extensive terminology
      development and maintenance experience. This paper discusses the process and
      status of SNOMED CT development and how the resources and expertise of both
      organizations are being used to develop this new terminological resource. The
      preliminary results of the merger process, including mapping, the merger of upper
      levels of each hierarchy, and attribute harmonization are also discussed.

PMID- 11825269
TI  - Monitoring quality requires knowing similarity: the NICLTS experience.
AB  - Laboratory tests can appear similar from the test names but may be vastly
      different in the way a result is achieved. Currently, for example, cervical
      cancer evaluation is moving from the traditional Papanicolaou smear to new smear
      preparation technologies and testing for human papillomavirus. Monitoring the
      quality of these three tests, and of all tests, requires that computers
      "understand" how these tests are similar and different. The National Inventory of
      Clinical Laboratory Testing Services (NICLTS) found that the approximately 20,000
      most commonly performed tests used combinations of 635 analytes and 1,699
      methods. These analytes and methods provide the base data for a semantic model
      that makes the requisite similarities and differences explicit. The semantic
      relationships, e.g. the method principle enabling a test and the nature of the
      substance tested, were evaluated against empirically derived, uni-dimensional
      relations. The resulting multi-dimensional semantic model expands our ability to
      monitor the quality of laboratory testing in the face of rapid change. Use of
      common terminology tools and representations enable the creation, expansion and
      reuse of this model beyond the needs of NICLTS.

PMID- 11825271
TI  - A framework for best practices in the deployment of departmental information
      systems.
AB  - In previous work, we conceptualized a departmental information system as
      embodying a flexible, but limited, model for the operation of a department, such
      as a laboratory or diagnostic imaging service. We further recognized these
      systems as tools that enable data-driven departmental management and function as
      feeder systems to enterprise management decision-support systems, and also embody
      a departmental and components of an enterprise management model. Finally, for
      systems that interact with professionals related to decision support, we note
      that such systems embody partial cognitive models that must be congruent with the
      professionals  cognitive processes (or professionals  cognitive behaviors must
      alternatively be congruent with the systems cognitive model), if these systems
      are to be supportive of the professionals  thinking and decision making. In this
      paper, we review this thinking and use it to derive proposed "best practices" in
      IS management, and system planning, procurement, implementation, and use.

PMID- 11825270
TI  - Development of an ontology to model medical errors, information needs, and the
      clinical communication space.
AB  - Medical errors are common, costly and often preventable. Work in understanding
      the proximal causes of medical errors demonstrates that systems failures
      predispose to adverse clinical events. Most of these systems failures are due to
      lack of appropriate information at the appropriate time during the course of
      clinical care. Problems with clinical communication are common proximal causes of
      medical errors. We have begun a project designed to measure the impact of
      wireless computing on medical errors. We report here on our efforts to develop an
      ontology representing the intersection of medical errors, information needs and
      the communication space. We will use this ontology to support the collection,
      storage and interpretation of project data. The ontology's formal representation
      of the concepts in this novel domain will help guide the rational deployment of
      our informatics interventions. A real-life scenario is evaluated using the
      ontology in order to demonstrate its utility.

PMID- 11825272
TI  - Comparing frequency of word occurrences in abstracts and texts using two stop
      word lists.
AB  - Retrieval tests have assumed that the abstract is a true surrogate of the entire
      text. However, the frequency of terms in abstracts has never been compared to
      that of the articles they represent. Even though many sources are now available
      in full-text, many still rely on the abstract for retrieval. 1,138 articles with
      their abstracts were downloaded from Journal of the American Medical Association,
      New England Journal of Medicine, the British Medical Journal, and the Lancet.
      Based on two stop word lists, one long and one short, content bearing words were
      extracted from the articles and their abstracts and the frequency of each word
      was counted in both sources. Each article and its abstract were tested using a
      chi-squared test to determine if the words in the abstract occurred as frequently
      as would be expected. 96% to 98% of the abstracts tested were not significantly
      different than random samples of the articles they represented. In these four
      journals, the abstracts are lexical, as well as intellectual, surrogates for the
      articles they represent.

PMID- 11825273
TI  - Student documentation of multiple diagnoses in family practice patients using a
      handheld student encounter log.
AB  - Patient encounter logs may provide an important early opportunity to assess
      beginning clinical students' attention to and experience with many medical
      problems. However, there are reasons to doubt the completeness of traditional
      paper logs. The family practice clerkship at Washington University in St. Louis
      has tried a series of structured paper and hand held computer logs in search of a
      format that permits students to completely document their patients' diagnoses.
      The clerkship introduced a Palm computer log, designed with PumaTech's Satellite
      forms (R), that uses patient demographics to select a diagnosis entry screen
      displaying many likely diagnoses as checkboxes. Additional drop lists and
      combinations of drop lists provide access to less common diagnoses. Students
      using this log document 2.4 problems per patient on average, and as many as 14
      problems in a single patient. Differences between students and preceptors are
      readily apparent. It is now possible to prepare students to rotate with specific
      preceptors, and to identify or predict gaps in experience that deserve remedial
      intervention.

PMID- 11825274
TI  - Real time information from bedside monitors as part of a web-based patient
      record.
AB  - Traditional paper-based Medical Records, and even most of their digital
      counterparts, represent historical patient information. On the other hand new
      generations of Point-of-Care devices can be connected to standard networks and
      deliver streams of real time data through an Intranet, or even the Internet.
      Vital signs provided by IP-based devices can then be viewed at remote stations.
      Merging both worlds, real time and historical, in the pursuit of a comprehensive
      EPR is the main challenge of the present project. The basic infra-structure is
      composed of three main components: an existing Web-based EPR viewing station1
      (Web-EPR); a fully integrated HIS/PACS system1; and a monitoring network (Siemens
      Infinity Network  2). Communication between the components was obtained by
      developing interfaces based on both HL7 and Siemens  protocols   the later only
      for waveforms. For the graphical display a web-browser-based application of the
      streamed signals was developed and integrated into the existing Web-EPR. This
      addition expanded the Web-EPR capabilities providing means to include real time
      signals and calculated parameters on the set of information already available.
      Some extra features of this project include: one-way SMS messaging of the
      parameters, interactive WAP access and a DICOM compliant storage of signal
      waveforms.

PMID- 11825275
TI  - Personalizing retrieval of journal articles for patient care.
AB  - We present a system for patient-specific searches on a database of medical
      journal articles which uses natural language techniques to match search results
      against patient records. We performed an information retrieval experiment
      comparing the performance of this system to two strategies, one of which uses
      extensive medical knowledge, while the other uses the same patient information
      our system has. The results show that our system is useful in improving recall
      over the strategy simulating a human specialist, and clearly outperforms the
      strategy of using the patient record content without intelligent processing.

PMID- 11825276
TI  - A comparison of a printed patient summary document with its electronic
      equivalent: early results.
AB  - Clinicians are always searching for efficient access to clinical data. The
      Regenstrief Medical Record System has a printed report that fills this niche:
      Pocket Rounds. Handheld computers may offer an alternative, but it is unclear how
      effectively a handheld computer can display such data. We surveyed residents and
      students on the general medicine services for their opinions regarding Pocket
      Rounds. Those with handheld computers were given access to an electronic version
      of Pocket Rounds-e-Rounds. We surveyed the subjects who used e-Rounds for their
      opinions on the electronic format and how it compared to paper. Users overall
      satisfaction with Pocket Rounds was 5.8 on a seven-point scale. User s overall
      satisfaction for e-Rounds was 5.6 on a seven-point scale. The most useful
      function was retrieval of lab data for both modalities. The results suggest that
      the electronic format is a viable alternative to paper. Further evaluation is
      needed, and we plan a prospective controlled trial to study this further.

PMID- 11825277
TI  - Building ICU artifact detection models with more data in less time.
AB  - As many as 86% of intensive care unit (ICU) alarms are false. Multiple signal
      integration of temporal monitor data by decision tree induction may improve
      artifact detection. We explore the effect of data granularity on model-building
      by comparing models made from 1-second versus 1-minute data. Models developed
      from 1-minute data remained effective when tested on 1-second data. Model
      development using 1-minute data means that more hours of ICU monitoring
      (including more artifacts) can be processed in less time. Compression of temporal
      data by arithmetic mean, therefore, can be an effective method for decreasing
      knowledge discovery processing time without compromising learning.

PMID- 11825278
TI  - Value of ICD-9 coded chief complaints for detection of epidemics.
AB  - To assess the value of ICD-9 coded chief complaints for early detection of
      epidemics, we measured sensitivity, positive predictive value, and timeliness of
      Influenza detection using a respiratory set (RS) of ICD-9 codes and an Influenza
      set (IS). We also measured inherent timeliness of these data using the cross
      correlation function. We found that, for a one-year period, the detectors had
      sensitivity of 100% (1/1 epidemic) and positive predictive values of 50% (1/2)
      for RS and 25% (1/4) for IS. The timeliness of detection using ICD-9 coded chief
      complaints was one week earlier than the detection using Pneumonia and Influenza
      deaths (the gold standard). The inherent timeliness of ICD-9 data measured by the
      cross-correlation function was two weeks earlier than the gold standard.

PMID- 11825279
TI  - Cardiac auscultatory recording database: delivering heart sounds through the
      Internet.
AB  - The clinical skill of cardiac auscultation, while known to be sensitive,
      specific, and inexpensive in screening for cardiac disease among children, has
      recently been shown to be deficient among residents in training. This decline in
      clinical skill is partly due to the difficulty in teaching auscultation.
      Standardization, depth, and breadth of experience has been difficult to reproduce
      for students due to time constraints and the impracticality of examining large
      numbers of patients with cardiac pathology. We have developed a web-based
      multimedia platform that delivers complete heart sound recordings from over 800
      different patients seen at the Johns Hopkins Outpatient Pediatric Cardiology
      Clinic. The database represents more than twenty significant cardiac lesions as
      well as normal and innocent murmurs. Each patient record is complete with a gold
      standard echo for diagnostic confirmation and a gold standard auscultatory
      assessment provided by a pediatric cardiology attending.

PMID- 11825280
TI  - Impact of a broadband interactive televisit/teleconsultation service for
      residential and working environments.
AB  - The availability of health care attention at the point of need is one of the key
      benefits of telemedicine. Home environment and working place are the two
      scenarios selected in this article to evaluate the impact of a televisit and
      teleconsultation service. 31 users from four different medical and patient groups
      participated in this study supported by European Commission ATTRACT project. The
      experiences, carried out in Madrid and Valencia Spanish sites, benefited from
      interactive broadband access networks to provide cost-effective telecare
      services. Key areas analyzed encompass systems usability, clinical outcomes,
      patients quality of care and infoethic issues. Services advantages were verified
      and compared both from patients and medical staff points of view. Main benefits
      pointed out refer to displacement reduction, better communication doctor/patient,
      provision of comfort or friendliness, more precise therapy follow-up and
      increases in patients  sense of well being.

PMID- 11825281
TI  - Hiding information by cell suppression.
AB  - Joining relational data can jeopardize patient confidentiality if disseminated
      data for research can be joined with publicly available data containing, for
      example, explicit identifiers. Ambiguity in data hinders the construction of
      primary keys that are of importance when joining data tables. We define two
      values to be indiscernible if they are the same or at least one of them is a
      special value. Two rows in a data table are indiscernible if their corresponding
      entries are indiscernible. We further define a table to be k-ambiguous if each
      row is indiscernible from at least k rows in the same table. We present two
      simple heuristics to make a table k-ambiguous by cell suppression, and compare
      them on example data.

PMID- 11825282
TI  - Requirements development for a patient computing system.
AB  - Critical parts of the software development life cycle are concerned with
      eliciting, understanding, and managing requirements. Though the literature on
      this subject dates back for several decades, practicing effective requirements
      development remains a current and challenging area. Some projects flourish with a
      requirements development process (RDP) that is implicit and informal, but this
      approach may be overly risky, particularly for large projects that involve
      multiple individuals, groups, and systems over time. At Partners HealthCare
      System in Boston, Massachusetts, we have applied a more formal approach for
      requirements development to the Patient Computing Project. The goal of the
      project is to create web-based software that connects patients electronically
      with their physician's offices and has the potential to improve care efficiency
      and quality. It is a large project, with over 500 function points. Like most
      technological innovation, the successful introduction of this system requires as
      much attention to understanding the business needs and workflow details as it
      does to technical design and implementation. This paper describes our RDP
      approach, and key business requirements discovered through this process. We
      believe that a formal RDP is essential, and that informatics as a field must
      include proficiencies in this area.

PMID- 11825283
TI  - Lightening the burden of the heavy regulatory hand an incentive for outpatient
      computer patient record.
AB  - However many benefits may be achieved for the organization, it is difficult to
      introduce a computer patient record (CPR) into an outpatient setting until the
      clinical practitioners themselves see direct benefit from the time invested. The
      ever increasing burden of regulation on health care in the outpatient setting
      includes (but is not limited to) guidelines for evaluation and management (E&M)
      coding, Local Medical Review Policy (LMRP) rules for diagnostic justification of
      tests and procedures and associated requirements for Advance Beneficiary
      Notification (ABN), and the rules for teaching physicians in academic settings.
      Achieving compliance with just the LMRP rules requires immediate access to an
      eight-inch-thick stack of manuals (ICD9, CPT, HCPCS, and LMRP), 4 inches of which
      is subject to update on a monthly basis. Accurate E&M coding is about as
      complicated as using the long form to do one s tax return. Without tools that can
      be provided by the CPR, these requirements add significant time to the patient
      encounter and significant risk of non-compliance and fines. We report our
      strategy for deploying the CPR as a strategy to keep clinicians from being
      overwhelmed by the rules, thereby allowing them to focus on healthcare. In the
      context of the CPR, and against all odds otherwise, the impact of the regulations
      can sometimes have beneficial and educational impacts on clinical care.

PMID- 11825284
TI  - Mapping between SNOMED RT and Clinical terms version 3: a key component of the
      SNOMED CT development process.
AB  - SNOMED RT and Clinical Terms Version 3 are two large, controlled medical
      terminologies that are being merged to form a new work titled SNOMED Clinical
      Terms (SNOMED CT). One of the first steps in this process was to create maps
      between semantically equivalent and proximate concepts in the two terminologies.
      Same-as and is-a relationships were used to map the descriptions from one
      terminology to concepts in the other terminology. The objectives were to identify
      semantically equivalent concepts in the two terminologies, to find the most
      semantically proximate is-a relationships for non-equivalent concepts, and to
      evaluate the synonymy in the source terminologies. The results suggest that the
      rate of semantic overlap between descriptions in SNOMED RT and CTV3 is
      approximately 28%. This article discusses the methodology, issues, and findings
      of the description mapping process.

PMID- 11825285
TI  - Developing a test collection for biomedical word sense disambiguation.
AB  - Ambiguity, the phenomenon that a word has more than one sense, poses difficulties
      for many current Natural Language Processing (NLP) systems. Algorithms that
      assist in the resolution of these ambiguities, i.e. which make unambiguous a
      word, or more generally, a text string, will boost performance of these systems.
      To test such techniques in the biomedical language domain, we have developed a
      Word Sense Disambiguation (WSD) test collection that comprises 5,000 unambiguous
      instances for 50 ambiguous UMLS Metathesaurus strings.

PMID- 11825286
TI  - Secure Internet video conferencing for assessing acute medical problems in a
      nursing facility.
AB  - Although video-based teleconferencing is becoming more widespread in the medical
      profession, especially for scheduled consultations, applications for rapid
      assessment of acute medical problems are rare. Use of such a video system in a
      nursing facility may be especially beneficial, because physicians are often not
      immediately available to evaluate patients. We have assembled and tested a
      portable, wireless conferencing system to prepare for a randomized trial of the
      system s influence on resource utilization and satisfaction. The system includes
      a rolling cart with video conferencing hardware and software, a remotely
      controllable digital camera, light, wireless network, and battery. A semi
      automated paging system informs physicians of patient s study status and
      indications for conferencing. Data transmission occurs wirelessly in the nursing
      home and then through Internet cables to the physician s home. This provides
      sufficient bandwidth to support quality motion images. IPsec secures
      communications. Despite human and technical challenges, this system is affordable
      and functional.

PMID- 11825287
TI  - Human factors research in anesthesia patient safety.
AB  - Patient safety has become a major public concern. Human factors research in other
      high-risk fields has demonstrated how rigorous study of factors that affect job
      performance can lead to improved outcome and reduced errors after evidence-based
      redesign of tasks or systems. These techniques have increasingly been applied to
      the anesthesia work environment. This paper describes data obtained recently
      using task analysis and workload assessment during actual patient care and the
      use of cognitive task analysis to study clinical decision making. A novel concept
      of "non-routine events" is introduced and pilot data are presented. The results
      support the assertion that human factors research can make important
      contributions to patient safety. Information technologies play a key role in
      these efforts.

PMID- 11825288
TI  - The capture and use of detailed process information in the Dialogix system for
      structured web-based interactions.
AB  - Information gathering tools, such as questionnaires, surveys, and structured
      interviews, are ubiquitously used in evaluating patients and systems. Despite
      their common use, there is a desperate need for better questionnaires in medical
      research and epidemiology, and an infrastructure that lets them be publicly
      scrutinized. Unfortunately, there has been no common platform that supports the
      deployment of arbitrary information gathering tools. Some psychiatric diagnostic
      interviews and epidemiological trials require sophisticated structured interviews
      containing complex branching logic, dynamic phrase composition, and multiple
      languages. The Dialogix system was developed to meet this need and facilitate the
      rapid definition and web-based deployment of structured human-computer
      interactions. This paper describes the content and process-related information
      captured by Dialogix, and how that information has been used in the development
      and deployment of two large epidemiological studies.

PMID- 11825289
TI  - Integrating existing drug formulation terminologies into an HL7 standard
      classification using OpenGALEN.
AB  - Many terminologies exist for the form of drugs--i.e. tablets, capsules, sprays,
      suppositories, etc. However, they have surprisingly different content. To
      communicate medication messages effectively, a mechanism is needed to translate
      between these existing terminologies. An ontological approach, based on
      techniques developed by OpenGALEN, has been used to build a drug form terminology
      for HL7 version 3. It integrates existing terminologies from commercial drug
      information vendors and regulatory authorities, and provides a framework for
      translating between them. To date, term sets have been included from First
      DataBank, the FDA, Multum and Micromedex, to produce a terminology of 820
      concepts. The approach is made practical by distributing the knowledge
      engineering effort to volunteers with experience of the domain, and then
      integrating the knowledge into a logically consistent classification.

PMID- 11825290
TI  - The Rapid Syndrome Validation Project (RSVP).
AB  - The Rapid Syndrome Validation Project (RSVP) is a collaboration of several
      institutions: Sandia and Los Alamos National Laboratories, the University of New
      Mexico Department of Emergency Medicine, and the NM Department of Health Office
      of Epidemiology. RSVP is a system that operates at the intersection of individual
      health care providers, public health and bioterrorism. Physicians quickly enter
      clinical and demographic information on patients exhibiting symptoms and signs of
      the syndromes of interest. It provides early warning and response to emerging
      biological threats, as well as emerging epidemics and diseases. RSVP provides
      real time clinical information to the provider and any other potential user such
      as the DOH, about current symptoms, disease prevalence and location. The system
      also serves as a mechanism for the Department of Health to inform health care
      providers of health alerts and to facilitate the process of collecting data on
      reportable diseases. We describe here the purpose an the architecture of a
      network-based surveillance system that is currently implemented in an Emergency
      Department.

PMID- 11825291
TI  - Molecular identification using flow cytometry histograms and information theory.
AB  - Flow cytometry is a common technique for quantitatively measuring the expression
      of individual molecules on cells. The molecular expression is represented by a
      frequency histogram of fluorescence intensity. For flow cytometry to be used as a
      knowledge discovery tool to identify unknown molecules, histogram comparison is a
      major limitation. Many traditional comparison methods do not provide adequate
      assessment of histogram similarity and molecular relatedness. We have explored a
      new approach   applying information theory to histogram comparison, and tested it
      with histograms from 14 antibodies over 3 cell types. The information theory
      approach was able to improve over traditional methods by recognizing various non
      random correlations between histograms in addition to similarity and providing a
      quantitative assessment of similarity beyond hypothesis testing of identity.

PMID- 11825292
TI  - Modeling the effects of epidemics on routinely collected data.
AB  - The use of routinely collected data, such as absenteeism, to provide an early
      warning of an epidemic will depend on better understanding of the effects of
      epidemics on such data. We reviewed studies in behavioral medicine and health
      psychology in order to build a model relating known factors related to human
      health information and treatment seeking behavior and effects on routinely
      collected data. This review and modeling effort may be useful to researchers in
      early detection, simulation, and response policy analysis.

PMID- 11825294
TI  - Restructuring the electronic medical record to incorporate full digital signature
      capability.
AB  - The security of Electronic Medical Records can be enhanced by the addition of
      digital signatures that guarantee data integrity, authenticate the signer, and
      establish non-repudiation through the use of public key encryption. The task is
      complicated by the contribution of multiple providers to an encounter and the
      entry of data at multiple points in time Dividing encounters into an episode of
      care and redesigning the data model of the EMR will facilitate full signature
      capabilities. Generation of digital signatures is best accomplished using
      microprocessors on smart cards that control visibility of the private keys and
      assist in user authentication. The Java Programming Language including
      cryptography extensions and a smart card API is a useful tool for adding digital
      signature to an EMR. Inter-operability of signatures and continuity of signature
      will require attention to standards and preservation of cryptography and
      authentication certificate archives. Digital signatures will need to accommodate
      changes in data storage formats when information is transported between EMR
      systems using XML or other transaction standards because the original signatures
      will not validate if the data storage format changes. The costs of adding digital
      signature to EMR mandates serious examination of the business case for digital
      signature within an EMR as compared with transactions such as electronic
      prescriptions. At present, there is no regulatory requirement for digital
      signature of an EMR.

PMID- 11825293
TI  - Structured data management--the design and implementation of a web-based video
      archive prototype.
AB  - In response to the lack of readily available multimedia rich medical knowledge
      sources to support medical education and patient care, we designed and
      implemented a web-based video publishing platform. In order to promote the
      development of high-quality, up-to-date educational content, we have devised a
      scalable structure that allows online submissions and continuous updating of
      video and accompanying textual descriptions. Our goal is to enable experts in
      varied medical domains to collaborate in the construction of a video library
      using an intuitive web-based interface. Neurologists at Stanford built a well
      annotated neurology video collection that initially emphasized childhood and
      adult movement disorders. The collection may be accessed either as a stand-alone
      resource or as part of the Stanford Skolar MD, an integrated online medical
      knowledge provider. This manuscript discusses the design framework and
      implementation details of structured media content development. We present
      examples illustrating media data collection, content indexing using UMLS
      concepts, media storage, and web presentation.

PMID- 11825295
TI  - The contribution of morphological knowledge to French MeSH mapping for
      information retrieval.
AB  - MeSH-indexed Internet health directories must provide a mapping from natural
      language queries to MeSH terms so that both health professionals and the general
      public can query their contents. We describe here the design of lexical knowledge
      bases for mapping French expressions to MeSH terms, and the initial evaluation of
      their contribution to Doc'CISMeF, the search tool of a MeSH-indexed directory of
      French-language medical Internet resources. The observed trend is in favor of the
      use of morphological knowledge as a moderate (approximately 5%) but effective
      factor for improving query to term mapping capabilities.

PMID- 11825296
TI  - Moving towards rational pharmacological management of pain with an improved
      classification system of pain.
AB  - Recognition that untreated pain can have serious deleterious effects has lead to
      significant resources being devoted towards understanding physiology, controlling
      nociception and implementing standards that promise to improve treatment of pain.
      Recently, improved knowledge and the appreciation of the need for a
      polypharmaceutical approach has lead to an appreciation that the classification
      of pain syndromes is the best approach towards rationalising treatment
      approaches. Older classification approaches such as acute and chronic,
      neuropathic, or nociceptive have not been universally useful for the clinician
      [1]. These classification schemes do not recognise that patients with pain often
      have mixed pain syndromes and do not fall neatly into these schemes. In addition,
      these classification schemes cannot represent newer advances in the understanding
      of pain and its physiology. Due to the growing variety of treatment approaches,
      classification of pain syndromes is often the best first step towards
      understanding a patient's pathophysiological process, initiating appropriate
      treatment and improving patient outcomes.

PMID- 11825297
TI  - Prospects for the treatment of Parkinson's disease using neurotrophic factors.
AB  - Parkinson's disease (PD) is a debilitating neurodegenerative condition that is
      characterised by a progressive loss of dopaminergic neurones of the substantia
      nigra pars compacta (SNpc) and the presence of alpha-synuclein cytoplasmic
      inclusions (Lewy bodies). Cardinal symptoms include tremor, bradykinesia, and
      rigidity, although cognitive and autonomic disturbances are not uncommon.
      Pharmacological treatment targeting the dopaminergic network is relatively
      effective at ameliorating these symptoms, especially in the early stages of the
      disease, but none of these therapies are curative and they generate their own
      problems. As dopaminergic neuronal death in PD occurs in a gradual manner, it is
      amenable to treatments that can either protect remaining dopaminergic neurones or
      prevent death of those neurones that have begun to die. Use of neurotrophic
      factors is a potential candidate, as various factors have been shown to increase
      dopaminergic neuronal survival in culture and promote survival and axonal growth
      in animal models of PD. Glial cell line-derived neurotrophic factor (GDNF) is
      currently the most effective substance that has been intensively studied and
      shown to have a specific 'dopaminotrophic' effect. This review will therefore
      focus on studies that have investigated GDNF and discuss the potential for
      neurotrophic factor treatment in PD.

PMID- 11825298
TI  - Tobacco addiction and pharmacological interventions.
AB  - Even though its health consequences are well known, tobacco use continues to kill
      millions of smokers worldwide every year. In the US alone, tobacco use kills >
      430,000 people each year. The global mortality toll is approximately 5 million
      annually and this is increasing. It is the powerful grip of tobacco addiction
      that sustains high levels of daily smoke intake and persistent smoking, with >
      90% of all cigarette smokers who quit, resuming smoking within 1 year. Tobacco
      addiction, which places tremendous health and economic burdens on individual
      societies, is also becoming a global epidemic. Although tobacco addiction is a
      complex phenomenon, it is treatable and several effective medications are now
      available. In the mid-1980s, the US FDA approved nicotine gum, the first of these
      effective pharmacological aids. Other effective medications have subsequently
      become available, including nicotine transdermal patches, nasal spray, oral
      vapour inhaler, sublingual nicotine tablets and bupropion. These medications and
      the potential for development of new medications will be reviewed.

PMID- 11825299
TI  - Considerations in the treatment of anxiety disorders: a pharmacoeconomic review.
AB  - Anxiety disorders are a group of common mental disorders that impose a
      significant economic burden on the healthcare system and society. For this review
      of published literature on the pharmacoeconomics of treating anxiety disorders,
      various studies of the cost, resource use and the economic outcomes of
      pharmacological treatment were examined. Numerous studies have been published
      that document how the excessive costs associated with anxiety disorders,
      especially panic disorder, result from a combination of factors including under
      recognition and misdiagnosis of the problem by primary healthcare providers, high
      medical resource utilisation including unnecessary or inappropriate diagnostic
      tests and high levels of medical help-seeking behaviour by patients. Little
      information has been available on the economic effects of pharmacotherapy for
      anxiety disorders but recent studies have shown that selective serotonin re
      uptake inhibitors (SSRIs) are associated with a shift in medical resource
      utilisation (lower rates of emergency department and laboratory visits) which can
      potentially result in decreased healthcare expenditures. Facilitating an
      increased awareness among primary healthcare providers of the anxiety disorders
      and utilising appropriate diagnostic and treatment strategies can benefit
      patients while providing more efficient and effective healthcare spending leading
      to an overall reduction in the burden of disease.

PMID- 11825300
TI  - Antipsychotic medication: effects on regulation of glucose and lipids.
AB  - Since the introduction of chlorpromazine in the 1950s, antipsychotics have been
      used for the treatment of schizophrenia. The phenothiazines were followed by the
      butyrophenones, particularly haloperidol. With all the movement disorder side
      effects of these medications (extrapyramidal syndrome, akathisia, tardive
      dyskinesia), the pharmaceutical industry has gradually released atypical
      antipsychotics. This class includes clozapine (released in the USA in 1990),
      risperidone (1994), olanzapine (1996), quetiapine (1998) and ziprasidone (2001).
      However, the rate of diabetes mellitus in patients with schizophrenia appeared to
      increase with the availability of this class of medications. In reviewing rate
      and degree of changes in weight, glucose control and lipid levels induced by
      typical and atypical antipsychotics, it was found that in contrast to case
      reports, there is a dearth of retrospective, open and controlled studies.
      However, in studies as early as 1964, significant weight increases were found to
      be associated with use of chlorpromazine. While the phenothiazines may have some
      effect on patients with chemical diabetes, there is little evidence of the
      typical antipsychotics producing diabetes mellitus de novo, or worsening diabetes
      that is already been discovered. Ziprasidone appears to be the antipsychotic with
      the most beneficial combination of effects: no weight gain, no change in glucose
      utilisation and reductions in cholesterol and serum triglycerides (TGs).

PMID- 11825301
TI  - Pharmacotherapy for post-traumatic stress disorder: a comprehensive review.
AB  - Significant advances have been made in the past 5 years in defining efficacious
      treatments for post-traumatic stress disorder (PTSD). Currently, sertraline is
      the first and only FDA-approved medication for this complex and often chronic
      illness. Other serotonergic antidepressants, such as paroxetine, fluoxetine and
      nefazodone, have well-controlled or replicated open-label evidence of efficacy.
      Anticonvulsants are also being studied as potential alternatives to treatment.
      Finally, atypical antipsychotic medications have shown promise in open-label
      trials. Clearly, more controlled studies are needed. This is especially true in
      males and in combat trauma-induced PTSD, where the effects of pharmacotherapy are
      less robust than in females or civilian trauma-induced PTSD. Also, there are
      virtually no data on pharmacotherapy for acute stress reaction or for PTSD in
      children. Future directions for research may focus on combination treatment in
      the more treatment-resistant patient populations.

PMID- 11825302
TI  - Anticonvulsants in the treatment of mood disorders: assessing current and future
      roles.
AB  - Anticonvulsants are frequently used in the treatment of affective illnesses,
      especially for patients refractory to or intolerant of other treatments. The
      differential therapeutic roles of anticonvulsants, however, remain largely
      undetermined. The author reviews the available efficacy data for carbamazepine,
      oxcarbazepine, valproate, lamotrigine, gabapentin and topiramate. Valproate is
      efficacious in the monotherapy of acute manic presentations but confirmatory
      evidence of the efficacy of valproate in long-term maintenance has been elusive.
      Valproate and possibly carbamazepine, may provide a therapeutic advantage over
      lithium in non-classic bipolar conditions such as mixed mood states and rapid
      cycling conditions. Lamotrigine is unique among the anticonvulsants in its
      monotherapy efficacy for bipolar I depression. Emerging data also suggest a role
      for lamotrigine in the adjunctive treatment of depressive mixed states and rapid
      cycling conditions in the absence of prominent manic symptoms. Controlled trials
      have found gabapentin ineffective for acute mania and refractory bipolar
      conditions. The role of gabapentin in the treatment of other aspects of affective
      illness remains uncertain. Definitive statements regarding the differential
      psychotropic use of topiramate and oxcarbazepine are not possible, though active
      investigation is underway to better characterise the utility of topiramate. The
      author suggests that current diagnostic models utilised in controlled trials may
      limit identification of differential therapeutic benefits. Caution is advised in
      generalising from the ability or inability of an agent to demonstrate antimanic
      activity. Future studies of newer anticonvulsants should include dimensional
      perspectives and soft bipolar presentations, as the greatest contribution of the
      newer anticonvulsants may be in treatment of mood conditions other than acute
      mania.

PMID- 11825303
TI  - Antiplatelet therapy in secondary stroke prevention.
AB  - Stroke is the third leading cause of death in the United States. Antiplatelet
      agents are the mainstays of ischaemic stroke prevention. The therapies
      recommended for initial therapy include aspirin (50 - 325 mg) daily, the
      combination of aspirin (25 mg) and extended-release dipyridamole (200 mg) b.i.d.,
      or clopidogrel (75 mg) daily. Ticlopidine 250 mg b.i.d. is approved for stroke
      prevention but is no longer a first-line therapy. This article reviews the
      literature on antiplatelet agents for secondary stroke prevention.

PMID- 11825304
TI  - Perspectives in the therapeutic use of leptin.
AB  - The cloning and characterisation of the protein encoded by the ob gene, called
      leptin, has represented an enormous advance in the knowledge we have at the
      present time on the control of appetite and the regulation of body weight. Animal
      experiments have shown that this adipocyte-derived hormone informs the
      hypothalamus about the magnitude of fat stores and induces changes in eating
      behaviour and thermogenesis directed to maintain nutritional homeostasis. Besides
      the CNS and adipose tissue, other tissues like the gonads, adrenals, pancreas,
      blood vessels, immune cells and bone are also targets for leptin action, setting
      the basis for the pleiotropic character of leptin. In contrast to ob(-)/ob(-)
      mice, which have leptin deficiency, obese patients usually exhibit
      hyperleptinaemia due to leptin resistance of uncertain aetiology. Patients with
      congenital leptin deficiency show a dramatic response to recombinant leptin
      therapy in terms of body weight and fat reduction. However, in contrast to
      animals, no thermogenic effect has been demonstrated in humans treated with
      leptin. Leptin-resistant obese subjects display a heterogeneous response to
      leptin treatment, though some patients achieve a significant weight loss when
      receiving high doses. New formulations are being tried with different success
      rates. Before leptin can play a role in the treatment of obesity, more studies
      are needed to discover which is the adequate dose, which the best route and form
      of administration and how we can select the patients who will benefit from this
      particular therapy. The development of new leptin analogues with high penetrating
      capacity to cross the blood-brain barrier and the investigation of other
      approaches to overcome the leptin resistance are awaited. Future applications of
      leptin may be directed to the treatment of infertility, wound healing and bone
      remodelling among others.

PMID- 11825305
TI  - The pharmacological management of drug-induced rheumatic disorders.
AB  - Many drugs can induce adverse effects such as rheumatoid disorders, which we need
      to be aware of in order to best detect and manage them. New drugs are constantly
      entering the marketplace and can cause an increasing number of disorders. Through
      this article, we review the prevention and pharmacological management of drug
      induced rheumatic disorders. These include articular and peri-articular
      manifestations induced by fluoroquinolones, retinoids, cyclosporin, drug-induced
      disorders of bone metabolism such as corticosteroid-induced osteoporosis and drug
      induced osteomalacia, and multisystemic manifestations including drug-induced
      lupus and arthritis induced by vaccinations and cytokines.

PMID- 11825306
TI  - Aspects of the treatment of Turner syndrome.
AB  - Several issues have to be considered when taking care of girls and women with
      Turner syndrome. During childhood, short stature is the primary concern and
      treatment with growth hormone (GH) is now widely used, often in conjunction with
      the androgen, oxandrolone. Recent studies indicate that doses used previously in
      the treatment of short stature have been too small. Induction of puberty should
      be performed at an appropriate age with reference to the peers of the patient. In
      adulthood, female sex hormone substitution should be offered to possibly prevent
      the increased morbidity seen in Turner syndrome, which consists of increased risk
      of fractures and osteoporosis, a clustering of diseases like ischaemic heart
      disease, hypertension, stroke and Type 2 diabetes, the latter entities being
      involved in the insulin resistance syndrome. Furthermore, hypothyreosis are often
      seen and the risk of Type 1 diabetes may also be increased. Congenital
      malformations of the heart are frequently seen in Turner syndrome, possibly
      increasing the risk of dissecting aorta aneurism. Liver enzymes are often
      elevated in Turner syndrome and there may be an increased risk of cirrhosis of
      the liver. Mortality does seem to be increased in Turner syndrome and women with
      the 'pure' 45,X karyotype do seem to be most severely affected. In the clinical
      practice of Turner syndrome, a careful monitoring of glucose and bone metabolism,
      weight, thyroid function and blood pressure should be performed. A cardiovascular
      risk profile should be determined and the patient informed concerning risks and
      benefits from sex hormone replacement therapy. Based on the available literature,
      sex hormone replacement therapy is highly recommended, although at present there
      are no longitudinal data documenting the long-term positive effect of sex steroid
      substitution. However, hypogonadism is expected to explain at least part of the
      decreased lifespan found in Turner syndrome. Since general physicians encounter
      Turner patients infrequently, it is recommended that the care and treatment of
      Turner syndrome is centralised.

PMID- 11825307
TI  - Review of botulinum toxin type A and its clinical applications in migraine
      headache.
AB  - Botulinum toxin type A (BTX-A) has been used successfully for many disorders
      related to excessive muscle contraction. It works, in part, by causing a dose
      dependent, reversible muscle relaxation. BTX-A has also been used for migraine
      prevention. The mechanism by which BTX-A acts in migraine is probably unrelated
      to its effect on muscle relaxation. BTX-A may have a distinct antinociceptive
      mechanism, either through action on the muscle spindles or through a direct
      effect on the central nervous system. Several trials and case reports have
      demonstrated the safety and efficacy of BTX-A in migraine headache. BTX-A is
      distinct from other preventive medications. Adverse events (AEs) are rare and
      mild. BTX-A is convenient, since the dosing interval may be 3 months or longer.
      However, before BTX-A can be considered a first-line agent for migraine, larger
      studies need to be conducted to determine optimum dosing and administration sites
      as well as patient characteristics that are predictive of response.

PMID- 11825308
TI  - Ziprasidone: profile on safety.
AB  - Ziprasidone (Geodon, Pfizer) is the latest of a new class of atypical
      antipsychotics, following the release of clozapine, risperidone, olanzapine and
      quetiapine. It has a serotonin Type 2a/dopamine Type 2 (5-HT2a/D2) receptor (R)
      binding ratio of approximately 8:1; amongst the highest of its class.
      Furthermore, it is a potent 5-HT1aR agonist, and displays 5-HT1dR and 5-HT2cR
      antagonist activity, with unique effects on blocking the re-uptake of both 5-HT
      and noradrenaline (NE). Finally, ziprasidone has low-to-modest affinity for
      histamine (H1) and alpha 1-adrenoceptors and a negligible affinity for muscarinic
      (M1) Rs. This combination of effects may be responsible for its low rate of
      general adverse events, low rate of persistent prolactin elevation, low incidence
      of weight gain, low liability for inducing movement disorders, low rate of
      syncope and induction of decreases in lipid profile. Data on the effect of
      ziprasidone on the electrocardiogram (ECG) indicates a relatively higher degree
      of change in measure of QTc but no cases of mortality from overdoses, torsade de
      pointes (TdP) or excess in sudden and unexpected deaths.

PMID- 11825309
TI  - Lansoprazole: pharmacokinetics, pharmacodynamics and clinical uses.
AB  - Lansoprazole (Prevacid, TAP Pharmaceuticals, Inc.) is a substituted benzimidazole
      that inhibits gastric acid secretion. This agent is approved for the short-term
      treatment of erosive reflux oesophagitis, active gastric ulcer, active duodenal
      ulcer and the treatment of non-steroidal anti-inflammatory drug (NSAID)-induced
      gastric and duodenal ulcers. It is also approved for the long-term treatment of
      healed reflux oesophagitis, healed duodenal ulcer, the treatment of
      hypersecretory conditions such as Zollinger-Ellison syndrome and the eradication
      of Helicobacter pylori as a component of triple therapy with lansoprazole,
      clarithromycin and amoxicillin, or dual therapy with lansoprazole and
      amoxicillin. Its mechanism of action is to selectively inhibit the membrane
      enzyme H+/K+ ATPase in gastric parietal cells. In clinical trials, lansoprazole
      is more effective than placebo or histamine (H2)-receptor antagonists in the
      treatment of reflux oesophagitis. Lansoprazole administered at a dose of 30 mg
      daily produced faster relief of symptoms and superior healing rates in patients
      with gastric or duodenal ulcers or reflux oesophagitis than H2-receptor
      antagonists. A daily dose of 30 mg lansoprazole reduced epigastric pain faster
      than omeprazole 20 mg daily in patients with peptic ulcer disease but healing
      rates at 4 and 8 weeks were similar with both agents at these dosages.
      Lansoprazole was more effective than H2-receptor antagonists in patients with
      Zollinger-Ellison syndrome and produced similar treatment outcome to omeprazole.
      Lansoprazole in combination with clarithromycin and amoxicillin produced similar
      rates of eradication of H. pylori. In clinical trials, lansoprazole is well
      tolerated and has a low frequency of side effects similar to that of H2-receptor
      antagonists or omeprazole.

PMID- 11825310
TI  - Oseltamivir: a clinical and pharmacological perspective.
AB  - Oseltamivir is the ethyl ester prodrug of the antiviral molecule, oseltamivir
      carboxylate, a potent and selective inhibitor of influenza A and B neuraminidase
      (NA) (sialidase). It is highly bioavailable in capsule and suspension
      formulations and, after conversion to the active metabolite in the liver,
      distributes throughout the body, including the upper and lower respiratory tract.
      Oseltamivir carboxylate is 3% bound to human plasma proteins and eliminated
      through the kidneys by a first-order process as unchanged drug by glomerular
      filtration and tubular secretion by an anionic transporter system. Given these
      characteristics, its potential for adverse interactions with other drugs appears
      limited to those arising from competitive inhibition of excretion by the renal
      tubular epithelial cell anionic transporter. The terminal plasma elimination half
      life is 1.8 h in healthy adults. Renal clearance is inversely related to renal
      function and averages 23 h after oral administration in individuals with
      creatinine clearance < 30 ml/min. In vitro studies have demonstrated potent
      antiviral activity against all strains of influenza A and B tested including
      avian H5N1 and H9N2 strains recently implicated in human cases in Hong Kong.
      Studies of both experimental and naturally-occurring influenza in humans have
      demonstrated efficacy in both the prevention and treatment of influenza A and B
      infection. The drug is well-tolerated with the only clinically important side
      effect being mild gastrointestinal upset. Resistance has been uncommonly seen
      after clinical use; the highest incidence was 5.5% in children treated for
      influenza A infection for 5 days. Viruses that develop resistance appear to be
      less virulent in laboratory animals and to replicate less efficiently than parent
      strains. Although oseltamivir and the M2 ion channel inhibitors, amantadine and
      rimantadine, have not been directly compared in clinical trials, the greater
      breadth of spectrum of oseltamivir, its modest side effect profile compared to
      amantadine and its lesser propensity to engender the emergence of transmissible
      drug-resistant strains all suggest strongly that oseltamivir is a significant new
      agent for the prevention and treatment of influenza. A series of controlled
      trials comparing M2 ion channel inhibitor drugs and the new neuraminidase (NA)
      inhibitor agents are now needed to test this hypothesis and thereby to further
      advance the science of antiviral drug use to control influenza.

PMID- 11825312
TI  - Pharmacotherapy of intermittent claudication.
AB  - Intermittent claudication (IC) is leg muscle pain, cramping and fatigue brought
      on by exercise and is the primary symptom of peripheral arterial disease. The
      goals of pharmacotherapy for IC are to increase the walking capacity/quality of
      life and to decrease rates of amputation. In 1988, pentoxifylline was the only
      drug that had reasonable supportive clinical trial evidence for being beneficial
      in IC. Since then a number of drugs have shown benefit or potential in IC.
      Cilostazol, a specific inhibitor of phosphodiesterase 3 and activator of
      lipoprotein lipase, clearly increases pain-free and absolute walking distances in
      claudicants. However, cilostazol does cause minor side effects including
      headache, diarrhoea, loose stools and flatulence. Naftidrofuryl, a serotonin (5
      HT2) receptor antagonist and antiplatelet drug, is beneficial in claudicants.
      Inhibitors of platelet aggregation (including nitric oxide from L -arginine or
      glyceryl trinitrate) and anticoagulants (low molecular weight heparin,
      defibrotide) probably have both short and long-term benefits in IC. In addition,
      intravenous infusions of prostaglandins (PGs) PGE1 and PGI2 have an established
      role in severe peripheral arterial disease and the recent introduction of longer
      lasting and/or oral forms of the PGs makes them more likely to be useful in the
      IC associated with less severe forms of the disease. There are some exciting new
      approaches to the treatment of IC, including propionyl-L-carnitine and basic
      fibroblast growth factor (bFGF).

PMID- 11825311
TI  - Evidence for the efficacy and safety of tolterodine in the treatment of
      overactive bladder.
AB  - Overactive bladder (OAB) is a chronic and prevalent condition, the symptoms of
      which (urinary frequency and urgency, with or without urge incontinence) can
      exert a profound negative effect on a person's daily life activities. Tolterodine
      (Detrol in North America and Detrusitol in the rest of the world, Pharmacia), a
      competitive muscarinic antagonist, is the first agent of this class to be
      specifically developed for the treatment of OAB. This agent displays in vivo
      functional selectivity for the bladder over other tissues that contain muscarinic
      receptors (e.g., salivary glands, eye), which translates into good efficacy and
      tolerability in patients with OAB (including the elderly). Comparative,
      randomised, double-blind studies show that tolterodine (administered as immediate
      release [IR] tablets 2 mg b.i.d.) is as effective as oxybutynin (5 mg t.i.d.) in
      improving all of the troublesome symptoms of OAB but with a significantly lower
      incidence and severity of dry mouth. The advent of a new extended-release (ER)
      capsule formulation of tolterodine (4 mg) for convenient once-daily treatment
      builds upon these findings, with significantly improved efficacy for reducing
      urge incontinence episodes and a lower frequency of dry mouth relative to the
      existing IR tablet (2 mg b.i.d.). Tolterodine can therefore be considered a
      valuable, well-tolerated treatment option for patients with OAB, providing
      improvements in symptoms that are both clinically meaningful to patients and
      sustained during long-term treatment.

PMID- 11825313
TI  - Anti-oxidants-- a protective role in cardiovascular disease?
AB  - Established risk factors for cardiovascular disease (CVD), such as hypertension,
      smoking and diabetes mellitus, explain only some of the observed variation in
      clinical events. This has maintained interest in other nutritional and
      biochemical factors that might contribute to the underlying pathophysiology of
      CVD. All of these risk factors are associated with increased oxidative stress in
      the vessel wall, which may contribute to CVD by several mechanisms. Studies in
      animal models of CVD have suggested that natural and synthetic anti-oxidants can
      prevent the development of clinical end points. These observations have generated
      the hypothesis that anti-oxidant therapy might also prevent CVD in human
      populations. This has been supported by epidemiological studies showing a
      negative correlation between circulating concentrations or dietary intake of
      natural anti-oxidant vitamins and CVD event rate. Many studies have also
      demonstrated a beneficial effect of anti-oxidants on surrogate markers of CVD
      such as endothelial function and lipoprotein oxidation. However, the results of
      large prospective randomised controlled intervention trials, mostly involving
      vitamin E in patients at increased risk of CVD, have been disappointing and have
      failed to demonstrate the anticipated benefits. This paper will critically
      examine the evidence and try to offer some explanation for the apparent failure
      of animal and epidemiological data to translate into meaningful clinical
      benefits.

PMID- 11825314
TI  - Opportunities for the treatment of inflammation in cardiovascular disease.
AB  - Atherosclerosis, and the clinical presentation of atherosclerosis, both have
      their basic pathogenesis in inflammatory mechanisms. The use of mouse models of
      atherosclerosis has emphasised the importance of inflammation in atherogenesis
      and the use of serum markers of inflammation in epidemiological studies has shown
      the importance of inflammatory status in determining the presentation of
      atherosclerotic disease. Therapeutic opportunities will arise from the
      manipulation of these inflammatory mechanisms. Proof of this principle has been
      shown with the use of aspirin and statin drugs as well as the emerging roles for
      peroxisome proliferator-activated receptor (PPAR) agonists. It is likely that
      both refinement of existing anti-inflammatory agents and the identification of
      new inflammatory mechanisms will afford real opportunities for the treatment of
      atherosclerotic cardiovascular disease.

PMID- 11825315
TI  - Pharmacological approaches to preserving and restoring coronary endothelial
      function.
AB  - There is compelling evidence that the endothelium is critical to normal coronary
      vascular function and that endothelial dysfunction, generally indicated by an
      impairment of endothelium-dependent vasodilatation, is an important component of
      coronary artery disease (CAD). Endothelial cells synthesise and release a number
      of factors, including prostacyclin, nitric oxide (NO), endothelium-derived
      hyperpolarising factor (EDHF) and endothelin, which are important in the
      regulation of vascular tone and the control of platelet and leukocyte adhesion,
      aggregation and migration. NO appears to be the critical factor in the
      preservation of normal coronary vascular function and there is a well-established
      correlation between CAD and an impairment of NO activity. Thus, to preserve
      endothelial function, drugs have been used to either increase the synthesis of
      NO, or to decrease its breakdown. Fortuitously, compounds such as the HMG-CoA
      reductase inhibitors, angiotensin (AT) converting enzyme inhibitors (ACEIs), AT
      receptor antagonists and oestrogen, which have been introduced into clinical
      practice because of other beneficial effects, have also been shown to improve
      coronary endothelial function through a variety of mechanisms. In addition, L 
      arginine, the substrate for NO synthesis, and the anti-oxidants ascorbate and
      alpha-tocopherol, are able to increase NO synthesis and bioavailability
      respectively. Studies in experimental animals strongly support the ability of
      these agents to enhance the activity of endothelium-derived NO but clinical
      trials have failed to demonstrate reversal of established CAD. Whether these
      agents preserve endothelial function and prevent the development of CAD remains
      to be established.

PMID- 11825316
TI  - Current practice in the treatment of hyperlipidaemias.
AB  - Primary and secondary prevention trials for coronary heart disease (CHD) in
      hyperlipidaemic or so-called 'normolipidaemic' patients with drugs affecting
      lipid metabolism have clearly confirmed that even slight alterations in
      lipoprotein metabolism are major risk factors for CHD. The global cardiovascular
      risk must be determined before deciding to treat patients with drugs affecting
      lipid metabolism. Screening for dyslipidaemia consists of determining cholesterol
      (C), LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C) and triglyceride (TG)
      plasma levels and the decision to treat depends mainly on LDL-C plasma levels.
      Furthermore, secondary dyslipidaemia must be diagnosed and primary disease must
      be adequately treated. There are four classes of available lipid-regulating
      drugs: HMG-CoA reductase inhibitors (statins), bile acid sequestrants (resins),
      peroxisome proliferator-activated receptor-alpha (PPAR- alpha) activators
      (fibrates) and nicotinic acid. All four will be discussed in this review.
      Clinical trials have shown that drugs improving lipid metabolism reduce CHD
      relative risk from 24% (secondary prevention) to 37% (primary prevention) and the
      absolute risk from 2% (primary prevention) to 8.5% (secondary prevention). These
      studies indicate that the number of patients needed to be treated to economise
      one clinical event ranges from 12 (secondary prevention) to 50 (primary
      prevention). Clinical trials are currently testing the hypothesis that 'lower LDL
      C is better'.

PMID- 11825317
TI  - Angiotensin II receptor blockers for the treatment of hypertension.
AB  - The rising incidence of stroke, congestive heart failure (CHF) and end stage
      renal disease (ESRD) has signalled a need to increase awareness, treatment and
      control of hypertension. There continues to be a need for effective
      antihypertensive medications since hypertension is a major precursor to various
      forms of cardiovascular disease. The renin-angiotensin (AT) aldosterone system
      (RAAS) is a key component to the development of hypertension and can be one
      target of drug therapy. Angotensin II (ATII) receptor blockers (ARBs) are the
      most recent class of agents available to treat hypertension, which work by by
      inhibiting ATII at the receptor level. Currently, national consensus guidelines
      recommend that ARBs should be reserved for hypertensive patients who cannot
      tolerate angiotensin converting enzyme (ACE) inhibitors (ACEIs). ARBs, however,
      are moving to the forefront of therapy with a promising role in the area of
      renoprotection and CHF. Recent trials such as the The Renoprotective Effect of
      the Angiotensin-Receptor Antagonist Irbesartan in Patients with Nephropathy Due
      to Type 2 Diabetes Trial (IDNT), the Effect of Irbesartan on the Development of
      Diabetic Nephropathy in Patients with Type 2 Diabetes (IRMA2), and The Effects of
      Losartan on Renal and Cardiovascular Outcomes in Patients with Type 2 Diabetes
      and Nephropathy (RENAAL) study have demonstrated the renoprotective effects of
      ARBs in patients with Type 2 diabetes. The Valsartan Heart Failure Trial (Val
      HeFT) adds to the growing body of evidence that ARBs may improve morbidity and
      mortality in CHF patients. As a class, ARBs are well tolerated and have a lower
      incidence of cough and angioedema compared to ACEIs. This article reviews the
      differences among the ARBs, existing efficacy data in hypertension, and explores
      the role of ARBs in CHF and renal disease.

PMID- 11825319
TI  - Pre-eclampsia, diagnosis and treatment.
AB  - Pre-eclampsia is a multisystem disorder of pregnancy usually associated with
      raised blood pressure (BP) and proteinuria. The pathogenesis is not understood
      despite decades of research. Abnormal placentation related to immune mechanisms
      and maladaptation of the placenta may be the first step in the development of the
      disease. Although there are a number of risk factors and new innovatory tests
      (e.g., uterine artery Doppler) which can be used to predict pre-eclampsia, none
      fulfils standard diagnostic criteria. Of possible prophylactic value are
      antiplatelet agents, calcium supplementation and vitamins C and E. Prevention of
      eclampsia with magnesium sulfate is the subject of a current international
      randomised controlled trial (RCT), known as MAGPIE. Therapeutic strategies
      include avoidance of hypertensive injury and delivery of the baby and placenta.
      Further research into specific antihypertensive agents and conservative
      management strategies is required.

PMID- 11825318
TI  - Pharmacotherapy of hypertension in patients with diabetes mellitus.
AB  - The co-existence of hypertension and diabetes dramatically and synergistically
      increases the risk of microvascular and macrovascular complications. Overwhelming
      evidence supports aggressive treatment of hypertension in diabetic patients.
      However, only a small percentage of diabetic hypertensive patients reach their
      treatment goal of blood pressure (BP) < 130/80 mmHg. Tight BP control is not only
      cost-effective but also more rewarding than glycaemic control. The optimal goal
      of BP control in diabetics should be 130/80 mmHg. In subjects with diabetes and
      renal insufficiency, the BP should be lowered to 125/75 mmHg to delay the
      progression of renal failure. The choice of an antihypertensive agent should be
      based on proven effects on morbidity and mortality rather than on surrogate
      parameters such as lipid or glucose. Limited data suggests that an angiotensin
      converting enzyme inhibitor (ACEI) is the agent of choice, especially in those
      with proteinuria or renal insufficiency. beta-blockers (betaBs) can be the first
      line agent in diabetics with coronary heart disease, while thiazide diuretics
      (TD) and calcium-channel blockers (CCBs) are the second-line drugs. Angiotensin
      II-receptor blockers (ARBs) may be proven to be as effective as ACEIs in
      diabetics with hypertension. alpha-adrenergic antagonists (AAAs) should be
      avoided. Most hypertensive patients require more than one agent to control their
      BP. There is no evidence to support one combination regimen over others;
      nevertheless, a combination of an ACEI with a TD or a betaB may be the most cost
      effective regimens compared to other combinations.

PMID- 11825320
TI  - Anorexia in end-stage renal disease: pathophysiology and treatment.
AB  - Anorexia is a frequent complication of uraemic syndrome, which contributes to
      malnutrition in dialysis patients. Uraemic anorexia has been associated with many
      factors. This paper reviews the current knowledge about mechanisms responsible
      for uraemic anorexia, the treatments and new drugs used to control the loss of
      appetite. Traditionally, anorexia in dialysis patients has been considered as a
      sign of uraemic toxicity, therefore, two hypotheses have been proposed, the
      'middle molecule' and 'peak-concentration' hypotheses, both of which are still
      unproved. Recently, our group proposed the tryptophan-serotonin hypothesis, which
      is based on a disorder in the amino acid profile acquired in the uraemic status.
      This is characterised by low concentrations of large neutral and branched chain
      amino acids (LNAA/BCAA) in the cerebrospinal fluid. This situation permits a high
      level of tryptophan transport across the blood-brain barrier, causing an increase
      in the synthesis of serotonin (responsible for appetite inhibition). There are
      two main treatment targets for anorexia in dialysis patients. The first is to
      decrease the free plasma tryptophan concentration and transport across the blood
      brain barrier to the cerebrospinal fluid, thus decreasing the intracerebral
      serotonin levels. Nutritional formulae enriched with LNAA and BCAA have this
      effect. Secondly, plasma levels of cytokines with cachectin effect (TNF-alpha),
      should be decreased. This also induces a decrease in LNAA and BCAA levels. In
      this group are megestrol acetate, anti-TNF-alpha antibodies, thalidomide,
      pentoxifyilline, n-3 fatty acids and possibly nandrolone decanoate. Additionally,
      other targets should be explored including antagonists of cholecystokinin (a
      potent anorexigen retained by renal failure), analogues of neuropeptide Y (the
      most potent orexigen), cannabinoids, cyproheptadine, hydrazine sulfate. In
      conclusion, uraemic anorexia is a complex complication associated with
      malnutrition, high morbidity and mortality. The pharmacological treatment should
      address key points in the pathogenesis of uraemic anorexia, reducing intra
      cerebral concentration of serotonin with LNAA/BCAA oral diet formulae and the
      plasma levels of pro-inflammatory molecules. Others forms of treatment should
      also be explored.

PMID- 11825321
TI  - Pharmacotherapy of fungal eye infections.
AB  - Fungal eye infections are rare. Trauma associated with contamination by
      vegetative material, contact lens wear and long term corticosteroid use are
      common risk factors. The aims of treatment are to preserve visual function, which
      depends on the rapid diagnosis and efficient administration of appropriate
      antifungal therapy. This necessitates a clinical suspicion of fungal aetiology
      and the taking of appropriate smears and cultures as early as possible to
      identify the fungal organism. Currently there are three main classes of drugs
      available for use in fungal eye infections: polyenes, azoles as derivatives of
      imidazoles, and 5-fluorocytosine. Of the polyenes, amphotericin B, natamycin and
      nystatin are of clinical ophthalmic use. Based on better pharmacokinetic profiles
      and spectra of antifungal activity, the triazoles are the agents of choice.
      Successful treatment of fungal keratitis depends on early initiation of specific
      therapy consisting of topically-applied antifungal agents since topical
      administration is most likely to provide the best opportunity for achieving
      therapeutic corneal levels. Hence, the molecular weight of the various antifungal
      agents is of importance since it influences their ability to penetrate the
      corneal epithelium. Systemic administration may be necessary for resistant fungal
      ulcers. For fungal endophthalmitis, to preserve visual function and eliminate the
      fungal pathogen, topical, systemic and possibly intraocular antifungal therapy is
      used, although some do not recommend use of systemic agents for exogenous
      endophthalmitis.

PMID- 11825322
TI  - COX-2 inhibitors compared and contrasted.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) are the principal drug treatments
      for inflammation, pain and fever. They act primarily by inhibiting prostaglandin
      (PG) synthesis but this can cause adverse events (AEs). Since the discovery of
      two PG synthesising enzymes, COX-1 and COX-2, and the substantial evidence that
      sparing COX-1 is advantageous for gastric safety, great interest has focused on
      selective COX-2 inhibitors. Much of the impetus has come from the most recently
      developed compounds celecoxib and rofecoxib, which have shown spectacular sales
      growth. However, the older drugs etodolac, nimesulide and meloxicam, made before
      COX-2 was discovered, are also COX-1-sparing and have good GI safety and
      therapeutic activities. These five compounds show similarities and differences
      that are discussed in relation to aspects that include their uses, efficacy,
      actions and safety.

PMID- 11825323
TI  - Amiodarone -- waxed and waned and waxed again.
AB  - Amiodarone has been used as an anti-arrhythmic drug since the 1970s and has an
      established role in the treatment of ventricular tachyarrhythmias. Although
      considered to be a class III anti-arrhythmic, amiodarone also has class I, II and
      IV actions, which gives it a unique pharmacological and anti-arrhythmic profile.
      Amiodarone is a structural analogue of thyroid hormone and some of its anti
      arrhythmic properties and toxicity may be attributable to interactions with
      nuclear thyroid hormone receptors. The lipid solubility of amiodarone gives it an
      exceptionally long half-life. Oral amiodarone takes days to work in ventricular
      tachyarrhythmias, but iv. amiodarone has immediate effect and can be used in life
      threatening ventricular arrhythmias. Intravenous amiodarone administered after
      out-of-hospital cardiac arrest due to ventricular fibrillation improves survival
      to hospital admission. Many survivors of myocardial infarction (MI) die during
      the subsequent year, probably due to ventricular arrhythmia. Amiodarone reduces
      sudden death after MI and this benefit is predominantly observed in patients with
      preserved cardiac function. Sudden cardiac death, predominantly due to
      ventricular arrhythmias, is also commonly seen in patients with heart failure.
      The Grupo de Estudio de la Sobrevida en lsuficiencia Cardiaca en Argentina
      (GESICA) and Estudio Piloto Argentino de Muerte Subita y Amiodarona (EPAMSA)
      trials showed survival benefit of amiodarone in heart failure, whereas Congestive
      Heart Failure-Survival Trial of Anti-arrhythmic Therapy (CHF-STAT) did not.
      Subsequent meta-analysis established a survival benefit of amiodarone in heart
      failure. Implanted Cardioverter Def ibrillators (ICDs) also give survival benefit
      to patients at risk of sudden death. In patients with a history of ventricular
      fibrillation or haemodynamically-compromising ventricular tachycardia, ICDs have
      been shown to be superior to anti-arrhythmic drugs, principally amiodarone.
      Further analysis has been undertaken to ascertain which patients are most likely
      to benefit from ICDs, as these are more expensive than treatment with amiodarone.
      Patients with severely depressed ejection fractions should be the first to be
      considered for ICDs. A new indication for amiodarone is atrial fibrillation or
      flutter. Amiodarone is effective in chronic and recent onset atrial fibrillation
      and orally or iv. for atrial fibrillation after heart surgery. In atrial
      fibrillation amiodarone is more than or equi-effective with flecainide,
      quinidine, racemic sotalol, propafenone and diltiazem and therefore should be
      considered for first line therapy. Amiodarone is also safe and effective in
      controlling refractory tachyarrhythmias in infants and is safe after cardiac
      surgery.

PMID- 11825324
TI  - Insulin glargine: the first clinically useful extended-action insulin analogue.
AB  - Insulin glargine is a new extended-action insulin analogue, created by
      recombinant DNA modification of human insulin. Extension of the C-terminal of the
      B-chain with two arginine residues and the substitution of glycine for asparagine
      at position A-21 increases the isoelectric point, resulting in precipitation of
      the insulin at the injection site and a protracted absorption. Pharmacodynamic
      studies have demonstrated a prolonged metabolic profile without a pronounced peak
      and with a duration of action of 20 - 30 h. In clinical studies in people with
      Type 1 and Type 2 diabetes, insulin glargine has demonstrated improved pre
      breakfast blood glucose control and a reduction in the frequency of
      hypoglycaemia, especially nocturnal hypoglycaemia, in comparison with neutral
      protamine hagedorn (NPH) insulin. In addition, 24h glycaemic control in Type 2
      diabetes and treatment satisfaction may also be improved. However, whilst
      appearing achievable, insulin glargine has not yet demonstrated the ability to
      improve HbA(1c), though this may relate to inexperience in the use of the new
      compound. In order to fully exploit its metabolic advantages, it appears vital
      that the dose of insulin glargine should be titrated to achieve aggressive pre
      breakfast blood glucose targets beyond those achievable with NPH in the absence
      of nocturnal hypoglycaemia. Insulin glargine appears to be a promising new
      addition to the insulin family and with increased experience in its use,
      especially in combination with rapid-acting insulin analogues, its full benefits
      may be realised. The use of insulin glargine with a rapid-acting insulin analogue
      brings us the closest we have ever been to providing the physiological insulin
      replacement that has long been awaited.

PMID- 11825325
TI  - Sirolimus: a comprehensive review.
AB  - Sirolimus (Rapamune), Wyeth-Ayerst, Madison, NJ) is a new, potent,
      immunosuppressant that is emerging as a foundation for long-term
      immunosuppressive therapy in renal transplantation. The drug acts during both co
      stimulatory activation and cytokine-driven pathways via a unique mechanism:
      inhibition of a multifunctional serine-threonine kinase, mammalian target of
      rapamycin (mTOR). Although there is no a priori reason to assume it, sirolimus
      displays a synergistic interaction to enhance the efficacy of cyclosporin A
      (CsA). In trials wherein the concentrations of CsA and sirolimus were tightly
      controlled, rates of acute rejection episodes were < 10%, despite markedly
      reduced exposures to each agent. In pivotal multi-centre blinded dose-controlled
      trials, the rates of acute rejection episodes within 12 months following
      administration of 2 or 5 mg/day sirolimus in combination with CsA and steroids
      were reduced to 19 and 14%, respectively. Since the inhibitory effect of
      sirolimus disables virtually all responses to cytokine mediators due to the
      widespread involvement of mTOR in multiple signalling pathways, the agent is
      likely also to retard proliferation of endothelial and vascular smooth muscle
      cells, an important component of the immuno-obliterative processes associated
      with chronic rejection. The advantages of this unique therapeutic action combined
      with an intrinsic lack of nephrotoxicity are counterbalanced by myelosuppressive
      and hyperlipidaemic side effects. Ongoing studies are assessing whether the long
      term benefits of sirolimus to permit reduction in exposure to or elimination of
      calcineurin inhibitors ameliorate the progression of chronic nephropathy, the
      condition that erodes long-term renal transplant survival.

PMID- 11825326
TI  - Pancreatic cancer: the evolving role of systemic therapy.
AB  - Pancreatic adenocarcinoma is the fourth leading cause of cancer mortality in the
      US. The outcome for patients with pancreatic cancer has not essentially altered
      over the past few decades. Several new drugs with activity against pancreatic
      cancer have recently been identified for use in palliative settings. Of these,
      gemcitabine is the most widely used agent against the disease, but its benefit is
      very modest. Pilot Phase II studies combining gemcitabine with 5-fluorouracil (5
      FU), irinotecan, docetaxel or cisplatin show improved outcomes that need to be
      confirmed in randomised studies. Concurrent administration of gemcitabine and
      external beam radiation therapy (EBRT) for locally advanced pancreatic cancer is
      feasible and is currently undergoing efficacy evaluations. Current research in
      pancreatic cancer involves newer dosing schedules of gemcitabine, and
      combinations of gemcitabine with novel agents. Ultimately, better understanding
      of the molecular biology of pancreatic neoplasia will identify potential cellular
      targets for future development of new agents for pancreatic cancer.

PMID- 11825327
TI  - Pharmacotherapy of anaemia in cancer patients.
AB  - Anaemia is a common complication of cancer. The incidence is variable and depends
      on several factors. A linear correlation between haemoglobin levels and quality
      of life (QOL) parameters has been found. Erythropoiesis is a finely regulated
      responsive process and erythropoietin (EPO) is the most important factor
      influencing progenitor cell proliferation. Impaired EPO production is mediated by
      inflammatory cytokines liberated in cancer patients. For this reason, EPO has
      been proposed as an alternative to blood transfusions, which involve many
      hazards. EPO treatment has been found to be effective in preventing anaemia and
      reducing the need for blood transfusions, although it would be useful to identify
      high-risk patient subgroups who would benefit most from this expensive treatment.

PMID- 11825328
TI  - Rapid cycling bipolar disorder.
AB  - Rapid cycling bipolar disorder (RCBD) is defined in the fourth edition of the
      Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) as a type of manic
      depressive illness in which the patient experiences four or more episodes of
      mania and/or major depression per year. It was first reported as a consequence of
      the reduced effectiveness of lithium carbonate in the treatment and prophylaxis
      of this form of bipolar disorder (BD) in contrast to those with less frequent
      cycling. Among the anticonvulsants, there have been reports with different
      degrees of controlled data concerning carbamazepine, valproate, lamotrigine,
      topiramate, gabapentin and primidone. There is a paucity of double-blind studies,
      but what is available supports the use of lamotrigine. There is open data
      supporting the use of carbamazepine, valproate and topiramate. Regarding other
      classes, nimodipine may have specific utility in ultradian- (ultra-ultra-) or
      ultra-RCBD and there is double-blind data regarding the specific utility of
      olanzapine in RCBD. Low thyroid function may be a factor in development of RCBD;
      therapies aimed at elevating thyroid levels, even beyond the usual range, have
      frequently produced benefits in open trials. More research is needed into the
      possible therapeutic benefits of verapamil, bupropion, choline, light therapy and
      electroconvulsive therapy (ECT).

PMID- 11825329
TI  - New concepts in the drug therapy of Alzheimer's disease.
AB  - There are currently four compounds approved for use in the treatment of
      Alzheimer's disease (AD). These drugs are all cholinesterase (ChE) inhibitors,
      which are thought to provide predominantly symptomatic benefits by increasing the
      level of acetylcholine (ACh) in the synapse. Although there are slight
      differences in the mechanisms of action of these compounds, it remains to be
      determined whether any one of them has a significant therapeutic advantage over
      the others. Several other drugs have also been investigated for their potential
      use as either symptomatic or disease-modifying agents in the treatment of AD,
      with mixed results. Current therapeutic research is focused on addressing the
      underlying pathology of AD, in the hope of arresting or reversing the course of
      the disease. This review will provide an overview of the ChE inhibitors and other
      drugs used for treating the symptoms of AD, summarise the results of recent
      therapeutic trials, discuss directions of future research and outline the current
      treatment recommendations for AD.

PMID- 11825330
TI  - Botulinum toxin for the treatment of cervical dystonia.
AB  - Cervical dystonia (CD) manifests clinically through involuntary spasms of neck
      muscles, producing abnormal head and neck movements and postures, which is often
      associated with pain. CD is the most common form of focal dystonia presenting to
      movement disorders clinics. Chemodenervation with botulinum toxin (BTX) has
      become the first-line treatment for CD, producing satisfactory relief of symptoms
      in > 80% of cases. Unresolved issues that may impact on the overall results
      include the method of selection for injection sites (clinical vs.
      electromyography), dosing, dilution and the role and relative efficacy of the
      different BTX serotypes. A guiding therapeutic principle of BTX injections is to
      achieve optimal results with the lowest possible dosage and frequency of
      administration. This strategy is critical in order to keep the risk of
      immunoresistance at a minimum. Development of antibodies that block the effects
      of BTX, usually associated with frequent injections of high doses, is the main
      reason for secondary unresponsiveness to this treatment. Although the mechanism
      of denervation at the neuromuscular junction by BTX is relatively well
      understood, the role of changes in muscle spindles and myopathic pain mechanisms,
      as well as secondary changes at the level of the basal ganglia, thalamus and
      cortex and their role in response to BTX, all need further exploration.

PMID- 11825331
TI  - Potassium channel openers: therapeutic potential in cardiology and medicine.
AB  - Potassium (K(+)) channel openers (KCOs) define a class of chemically diverse
      agents that share a common molecular target, the metabolism-regulated ATP
      sensitive K(+) (K(ATP)) channel. In view of the unique function that K(ATP)
      channels play in the maintenance of cellular homeostasis, this novel class of ion
      channel modulators adds to existent pharmacotherapy with potential in promoting
      cellular protection under conditions of metabolic stress. Indeed, experimental
      studies have demonstrated broad therapeutic potential for KCOs, including roles
      as cardioprotective agents, vasodilators, bronchodilators, bladder relaxants,
      anti-epileptics, insulin secretagogues and promoters of hair growth. However,
      clinical experience with these drugs is limited and their place in patient
      management needs to be fully established.

PMID- 11825332
TI  - Review of risedronate in the treatment of osteoporosis.
AB  - Risedronate (Actonel, Procter & Gamble and Aventis) is a novel, orally
      administered pyridinyl bisphosphonate. Preclinical studies have shown that
      risedronate is a potent inhibitor of osteoclasts. Risedronate inhibited bone
      resorption and increased bone density in the spine and hip. Prospective,
      randomised, placebo-controlled trials (RCTs) in patients with postmenopausal
      osteoporosis (PMO) have demonstrated that risedronate decreased the risk of
      vertebral fractures by up to 49% and of non-vertebral fractures by up to 39% over
      3 years in postmenopausal women with one or more prevalent vertebral fractures.
      This reduction of the risk for vertebral fractures was significant from the first
      year of treatment (risk reduction up to 65%). Risedronate was the first
      bisphosphonate to be studied in a large RCT with prevention of hip fracture as
      the primary end point. In this study, risedronate reduced the risk of hip
      fracture by 40% in elderly women with low hip bone density and one clinical risk
      factor for hip fracture and by 60% in women with low bone density and a prevalent
      vertebral fracture at baseline. Risedronate was also effective in the prevention
      and treatment of bone loss in glucocorticoid-induced osteoporosis (GIO), with a
      positive effect on vertebral fractures within the first year. Risedronate was
      well-tolerated with a safety profile comparable to placebo in all clinical
      studies. Patients with a previous or current history of upper GI illness or who
      were taking NSAIDs or aspirin were not excluded from these studies. Importantly,
      the upper GI safety profile of risedronate was shown to be similar to that of
      placebo in endoscopic studies. There was no evidence of acute-phase reactions or
      primary mineralisation defects. The most appropriate dose of risedronate was 5
      mg/day.

PMID- 11825333
TI  - Current status and new developments with galantamine in the treatment of
      Alzheimer's disease.
AB  - Galantamine is a newly available cholinergic drug that offsets reductions in
      central cholinergic neurotransmission in Alzheimer's disease (AD) by specifically
      and reversibly inhibiting acetylcholinesterase (AChE) and by allosterically
      modulating nicotinic cholinergic receptors. The clinical impact of this latter
      mechanism of action has not been fully elucidated. Galantamine has favourable
      pharmacokinetic features including linear elimination kinetics, a relatively
      short half-life and high oral bioavailability. The efficacy of galantamine has
      been studied in an extensive clinical development program. During randomised,
      double-blind, placebo-controlled trials of up to 6 months' duration, galantamine
      16 and 24 mg/day consistently produced a broad spectrum of beneficial effects on
      cognitive and non-cognitive AD symptoms. Patients' cognition, global function and
      abilities to perform both instrumental and basic activities of daily living were
      maintained, the emergence of behavioural symptoms was postponed and apparent
      reductions in caregiver burden were seen. In long-term studies (> or = 12
      months), galantamine maintained cognitive and functional abilities at or near
      baseline levels for at least 12 months. Again, these benefits were associated
      with decreases in caregiver burden. The incidence of adverse events, which are
      typically mild or moderate in severity, is generally low with galantamine.
      Cholinergically mediated adverse events affecting mainly the gastrointestinal
      system can be minimised using the recommended slow dose-escalation regimen.
      Galantamine may therefore help reduce the overall burden and cost involved in
      caring for AD patients. Being approved for the treatment of mild-to-moderately
      severe AD in both the US and in Europe, with trials of its efficacy in other
      dementia types already yielding positive results, galantamine ranks as a first
      line therapy for dementia.

PMID- 11825334
TI  - Update on ropivacaine.
AB  - Long-acting local anaesthetics are primarily used in the practice of anaesthesia,
      particularly in regional anaesthesia and analgesia. Ropivacaine is a new long
      acting local anaesthetic that has been the focus of interest because of its
      increased cardiovascular safety compared with bupivacaine. Other advantages of
      ropivacaine over bupivacaine include a greater sensorimotor differential block
      and shorter elimination half-life (t(1/2)), with a lower potential for
      accumulation. The most important attribute of ropivacaine, however, is its
      increased margin of safety compared with bupivacaine when given in equal doses.
      Many post-marketing studies have focused on the comparisons of efficacy in blocks
      and toxicity profiles of bupivacaine versus ropivacaine. Recent animal toxicity
      studies confirm the results of original studies showing that ropivacaine has less
      cardiovascular toxicity than bupivacaine with respect to direct myocardial
      depression, success of resuscitation and arrhythmogenic potential when given in
      equal doses. Reduced cardiotoxicity may be a distinct characteristic of
      ropivacaine. A review of current literature suggests that, at clinically relevant
      doses, ropivacaine provides the lowest potential risk of cardiotoxicity for
      inadvertent intravascular injection. Studies are currently under way comparing
      ropivacaine with levobupivacaine, the latest addition to the group of long-acting
      local anaesthetics.

PMID- 11825335
TI  - The role of nevirapine in the treatment of HIV-1 disease.
AB  - Nevirapine (Viramune, Boehringer Ingelheim) is a non-nucleoside reverse
      transcriptase (RT) inhibitor (NNRTI) effective in the treatment of HIV-1 infected
      antiretroviral-naive and -experienced patients. Some recent studies have
      suggested that nevirapine-based regimens may have an efficacy similar to protease
      inhibitor (PI)-based regimens, at least in naive patients with CD4+ > 200 microl,
      while it lacks the drawbacks inherent in PI-containing regimens, such as
      lipodystrophy and metabolic alterations. Switching from a PI-containing regimen
      to a nevirapine-containing regimen seems to retain the virological response to
      therapy and it may also limit or reverse the development of some metabolic
      disorders induced by PIs. Nevirapine is also effective in preventing mother-to
      child transmission of HIV-1 disease and in the treatment of HIV-1 infected
      children. Nevirapine is well-tolerated, rash being the most common severe adverse
      effect observed. Hepatotoxicity may also appear with nevirapine, mainly in
      patients with chronic hepatitis C and/or altered liver function tests. This side
      effect may occasionally be life-threatening but it can be safely managed in most
      patients.

PMID- 11825336
TI  - A critical evaluation of the NICE guidelines for post-myocardial infarction
      prophylaxis. National Institute for Clinical Excellence.
AB  - The UK National Institute for Clinical Excellence (NICE) has recently published
      guidelines on prophylaxis for patients who have experienced a myocardial
      infarction (MI). Based on a previously commissioned extensive review of the
      literature, the recommendations are antiplatelet therapy, beta-blockers and
      angiotensin converting enzyme inhibitors (ACEIs) for all patients; statins for
      those with hypercholesterolaemia; spironolactone for those with moderate-to
      severe heart failure (HF); and insulin for those with diabetes. While there may
      be concerns about some of the details (eg., the possible adverse interaction
      between aspirin and ACEIs), comments on the use of statins for those with HF, the
      lack of advice on the choice of lipid-lowering therapy for those intolerent of
      statins, the dangers of spironolactone therapy and the practicality of intensive
      insulin treatment, the guidelines are firmly based on sound evidence of efficacy
      and cost effectiveness. The NICE guidelines should therefore stimulate the
      provision of resources to address the gap between current practice and these
      recommendations.

PMID- 11825337
TI  - Signal analysis of behavioral and molecular cycles.
AB  - BACKGROUND: Circadian clocks are biological oscillators that regulate molecular,
      physiological, and behavioral rhythms in a wide variety of organisms. While
      behavioral rhythms are typically monitored over many cycles, a similar approach
      to molecular rhythms was not possible until recently; the advent of real-time
      analysis using transgenic reporters now permits the observations of molecular
      rhythms over many cycles as well. This development suggests that new details
      about the relationship between molecular and behavioral rhythms may be revealed.
      Even so, behavioral and molecular rhythmicity have been analyzed using different
      methods, making such comparisons difficult to achieve. To address this
      shortcoming, among others, we developed a set of integrated analytical tools to
      unify the analysis of biological rhythms across modalities. RESULTS: We
      demonstrate an adaptation of digital signal analysis that allows similar
      treatment of both behavioral and molecular data from our studies of Drosophila.
      For both types of data, we apply digital filters to extract and clarify details
      of interest; we employ methods of autocorrelation and spectral analysis to assess
      rhythmicity and estimate the period; we evaluate phase shifts using
      crosscorrelation; and we use circular statistics to extract information about
      phase. CONCLUSION: Using data generated by our investigation of rhythms in
      Drosophila we demonstrate how a unique aggregation of analytical tools may be
      used to analyze and compare behavioral and molecular rhythms. These methods are
      shown to be versatile and will also be adaptable to further experiments, owing in
      part to the non-proprietary nature of the code we have developed.

PMID- 11825338
TI  - The molecular genetic linkage map of the model legume Medicago truncatula: an
      essential tool for comparative legume genomics and the isolation of agronomically
      important genes.
AB  - BACKGROUND: The legume Medicago truncatula has emerged as a model plant for the
      molecular and genetic dissection of various plant processes involved in
      rhizobial, mycorrhizal and pathogenic plant-microbe interactions. Aiming to
      develop essential tools for such genetic approaches, we have established the
      first genetic map of this species. Two parental homozygous lines were selected
      from the cultivar Jemalong and from the Algerian natural population (DZA315) on
      the basis of their molecular and phenotypic polymorphism. RESULTS: An F2
      segregating population of 124 individuals between these two lines was obtained
      using an efficient manual crossing technique established for M. truncatula and
      was used to construct a genetic map. This map spans 1225 cM (average 470 kb/cM)
      and comprises 289 markers including RAPD, AFLP, known genes and isoenzymes
      arranged in 8 linkage groups (2n = 16). Markers are uniformly distributed
      throughout the map and segregation distortion is limited to only 3 linkage
      groups. By mapping a number of common markers, the eight linkage groups are shown
      to be homologous to those of diploid alfalfa (M. sativa), implying a good level
      of macrosynteny between the two genomes. Using this M. truncatula map and the
      derived F3 populations, we were able to map the Mtsym6 symbiotic gene on linkage
      group 8 and the SPC gene, responsible for the direction of pod coiling, on
      linkage group 7. CONCLUSIONS: These results demonstrate that Medicago truncatula
      is amenable to diploid genetic analysis and they open the way to map-based
      cloning of symbiotic or other agronomically-important genes using this model
      plant.

PMID- 11825339
TI  - Simultaneous intra/extravascular administration of antiproliferative agents as a
      new strategy to inhibit restenosis: the peak of reactive cell proliferation as a
      hallmark for the duration of the treatment.
AB  - BACKGROUND: Strictly intravascular approaches for the treatment of
      postangioplasty restenosis are effective in the intima and the inner parts of the
      media but may be insufficient to control redundant pathways in the more outer
      parts of the media and the adventitia. An inverse situation may occur
      subsequently to a strictly extravascular approach, like the recently suggested
      pericardial approach in pigs. We hypothesized that simultaneous
      intra/extravascular administration of anti-restenotic agents inhibits restenosis
      by blocking all stimulatory pathways in the entire arterial wall. METHODS: Fresh
      hearts of 25 domestic pigs were obtained from a local slaughterhouse. Left
      anterior descending coronary arteries (LAD) were harvested, cut into cylindric 5
      mm segments, and cultured as ex vivo porcine organ cultures (POCs). After 9 bar
      ballooning simultaneous intra/extravascular administration of high dose diltiazem
      (50 microg/mL) was carried out for a period of 1, 2, 3, 4, 5, 6, and 7 days. At
      day 7 and 28 proliferative activity (BrdU), neointimal thickening, and staining
      against smooth muscle alpha-actin and vWF was analysed. RESULTS: 7 days after
      ballooning administration of diltiazem for 4, 5, 6, and 7 days inhibited reactive
      cell proliferation by more than 50% (n.s.) as compared to control, 28 days after
      ballooning administration for 6 and 7 days inhibited neointimal thickening by
      more than 75% (p < 0.05). Simultaneous intra/extravascular administration of high
      dose diltiazem did not affect the expression of vWF in endothelial cells or
      smooth muscle alpha-actin in smooth muscle cells. CONCLUSIONS: Simultaneous
      intra/extravascular administration of high dose diltiazem (50 microg/mL) has to
      be maintained for at least 6 days to achieve a significant inhibition of
      neointimal thickening. The data demonstrate the importance of the maximal
      reactive cell proliferation (= day 7 in the POC-model) for the calculation of the
      duration of the treatment period.

PMID- 11825340
TI  - Right and left prefrontal transcranial magnetic stimulation at 1 Hz does not
      affect mood in healthy volunteers.
AB  - BACKGROUND: Prefrontal repetitive transcranial magnetic stimulation (rTMS) has
      been used to induce side-specific mood changes in volunteers and patients. To
      clarify inconsistencies between reports that used different stimulation
      frequencies, we conducted a controlled study with a low (1 Hz) frequency,
      comparing left with right-sided stimulation METHODS: Nineteen healthy volunteers
      received randomised left or right prefrontal rTMS at a frequency of 1 Hz and 100%
      of motor threshold in two sessions two weeks apart. RESULTS: There were
      significant improvements with TMS for performance in the digit symbol
      substitution and verbal fluency tests, but no change of mood on a number of
      measures. There was also a reduction of pulse rate after TMS. The only side
      specific TMS-effect was on mean arterial pressure, which decreased pressure after
      left, but not after right prefrontal TMS. CONCLUSIONS: Apart from the unexpected
      and so far unreplicated effect on mean arterial pressure, there were no side
      specific effects on mood in volunteers. It is unlikely that a simple laterality
      model of mood together with the assumed activating effect of higher and
      'quenching' effect of lower stimulation frequency can account for the effects of
      TMS on mood.

PMID- 11825341
TI  - Decreased insulin binding to mononuclear leucocytes and erythrocytes from dogs
      after S-nitroso-N-acetypenicillamine administration.
AB  - BACKGROUND: Nitric oxide (NO) and oxygen free-radicals play an important part in
      the destruction of beta-cells in auto- immune diabetes although the precise
      mechanism of interaction is still not known. This study was designed to examine
      any possible diabetogenic effect of NO by investigating any differences in
      cellular binding of insulin to its receptor on the cell membranes of erythrocytes
      and mononuclear leucocytes of dogs treated with the NO donor, S-nitroso-N
      acetylpenicillamine (SNAP) and controls treated with captopril. RESULTS: The
      result obtained showed decreased binding of insulin to its receptor on the cell
      membranes of erythrocytes and mononuclear leucocytes. Mononuclear leucocytes from
      SNAP-treated dogs had decreased ability to bind insulin (16.30 +/- 1.24 %) when
      compared to mononuclear leucocytes from captopril-treated controls (20.30 +/-
      1.93 %). Similar results were obtained for erythrocytes from dogs treated with
      SNAP (27.20 +/- 1.33 %) compared with dogs treated with captopril (34.70 +/- 3.58
      %). Scatchard analysis demonstrated that this decrease in insulin binding was
      accounted for by a decrease in insulin receptor sites per cell, with mononuclear
      leucocytes of SNAP-treated dogs having 55 % less insulin receptor sites per cell
      compared with those of captopril-treated controls (P < 0.05). Average affinity
      and kinetic analysis revealed a 35 % decrease in the average receptor affinity,
      with mononuclear leucocytes from captopril-treated controls having an empty site
      affinity of 12.36 +/- 1.12 x 10(-8) M(-1) compared with 9.64 +/- 0.11 x 10(-8) M(
      1) in SNAP-treated dogs (P < 0.05). CONCLUSION: These results suggest that acute
      alteration of the insulin receptor on the membranes of mononuclear leucocytes and
      erythrocytes occurred in dogs treated with S-nitroso-N-acetylpenicillamine. These
      findings suggest the first evidence of the novel role of NO as a modulator of
      insulin binding and the involvement of NO in the aetiology of diabetes mellitus.

PMID- 11825343
TI  - Supracervical hysterectomy versus total abdominal hysterectomy: perceived effects
      on sexual function.
AB  - BACKGROUND: Our investigation sought to compare changes in sexual function
      following supracervical hysterectomy (SCH) and total abdominal hysterectomy
      (TAH). METHODS: A retrospective chart review was performed to identify all
      patients who underwent supracervical hysterectomy or total abdominal hysterectomy
      at a tertiary care center. Patients who met criteria for participation were sent
      a one page confidential, anonymous questionnaire to assess sexual function
      experienced both pre- and postoperatively. A total of 69 patients in each group
      were eligible for participation. A multiple logistic regression model was used to
      analyze measured variables. RESULTS: Forty-eight percent (n = 33) of women
      undergoing a SCH returned the questionnaire, while 39% (n = 27) of those
      undergoing a TAH chose to participate. There were no significant demographic
      differences between the two groups. Patients who underwent TAH reported worse
      postoperative sexual outcome than SCH patients with respect to intercourse
      frequency, orgasm frequency and overall sexual satisfaction (P = 0.01, 0.03, and
      0.03, respectively). Irrespective of type of hysterectomy, 35% of patients who
      underwent bilateral salpingoophorectomy (BSO) with hysterectomy experienced worse
      overall sexual satisfaction compared to 3% of patients who underwent hysterectomy
      alone (P = 0.02). CONCLUSIONS: Our data suggest that TAH patients experienced
      worse postoperative sexual function than SCH patients with respect to intercourse
      frequency and overall sexual satisfaction. Irrespective of type of hysterectomy,
      patients who underwent bilateral salpingoophorectomy experienced worse overall
      sexual satisfaction.

PMID- 11825342
TI  - Blockade of maitotoxin-induced oncotic cell death reveals zeiosis.
AB  - BACKGROUND: Maitotoxin (MTX) initiates cell death by sequentially activating 1)
      Ca2+ influx via non-selective cation channels, 2) uptake of vital dyes via
      formation of large pores, and 3) release of lactate dehydrogenase, an indication
      of cell lysis. MTX also causes formation of membrane blebs, which dramatically
      dilate during the cytolysis phase. To determine the role of phospholipase C (PLC)
      in the cell death cascade, U73122, a specific inhibitor of PLC, and U73343, an
      inactive analog, were examined on MTX-induced responses in bovine aortic
      endothelial cells. RESULTS: Addition of either U73122 or U73343, prior to MTX,
      produced a concentration-dependent inhibition of the cell death cascade (IC50
      asymptotically equal to 1.9 and 0.66 microM, respectively) suggesting that the
      effect of these agents was independent of PLC. Addition of U73343 shortly after
      MTX, prevented or attenuated the effects of the toxin, but addition at later
      times had little or no effect. Time-lapse videomicroscopy showed that U73343
      dramatically altered the blebbing profile of MTX-treated cells. Specifically,
      U73343 blocked bleb dilation and converted the initial blebbing event into
      "zeiosis", a type of membrane blebbing commonly associated with apoptosis. Cells
      challenged with MTX and rescued by subsequent addition of U73343, showed enhanced
      caspase-3 activity 48 hr after the initial insult, consistent with activation of
      the apoptotic program. CONCLUSIONS: Within minutes of MTX addition, endothelial
      cells die by oncosis. Rescue by addition of U73343 shortly after MTX showed that
      a small percentage of cells are destined to die by oncosis, but that a larger
      percentage survive; cells that survive the initial insult exhibit zeiosis and may
      ultimately die by apoptotic mechanisms.

PMID- 11825344
TI  - Kefir consumption does not alter plasma lipid levels or cholesterol fractional
      synthesis rates relative to milk in hyperlipidemic men: a randomized controlled
      trial [ISRCTN10820810].
AB  - BACKGROUND: Fermented milk products have been shown to affect serum cholesterol
      concentrations in humans. Kefir, a fermented milk product, has been traditionally
      consumed for its potential health benefits but has to date not been studied for
      its hypocholesterolemic properties. METHODS: Thirteen healthy mildly
      hypercholesterolemic male subjects consumed a dairy supplement in randomized
      crossover trial for 2 periods of 4 wk each. Subjects were blinded to the dairy
      supplement consumed. Blood samples were collected at baseline and after 4 wk of
      supplementation for measurement of plasma total, low-density lipoprotein, and
      high-density lipoprotein cholesterol and triglyceride concentrations, as well as
      fatty acid profile and cholesterol synthesis rate. Fecal samples were collected
      at baseline and after 2 and 4 wk of supplementation for determination of fecal
      short chain fatty acid level and bacterial content. RESULTS: Kefir had no effect
      on total cholesterol, low-density lipoprotein cholesterol, high-density
      lipoprotein cholesterol or triglyceride concentrations nor on cholesterol
      fractional synthesis rates after 4 wk of supplementation. No significant change
      on plasma fatty acid levels was observed with diet. However, both kefir and milk
      increased (p < 0.05) fecal isobutyric, isovaleric and propionic acids as well as
      the total amount of fecal short chain fatty acids. Kefir supplementation resulted
      in increased fecal bacterial content in the majority of the subjects.
      CONCLUSIONS: Since kefir consumption did not result in lowered plasma lipid
      concentrations, the results of this study do not support consumption of kefir as
      a cholesterol-lowering agent.

PMID- 11825345
TI  - Attitudes of the Japanese public and doctors towards use of archived information
      and samples without informed consent: preliminary findings based on focus group
      interviews.
AB  - BACKGROUND: The purpose of this study is to explore laypersons' attitudes toward
      the use of archived (existing) materials such as medical records and biological
      samples and to compare them with the attitudes of physicians who are involved in
      medical research. METHODS: Three focus group interviews were conducted, in which
      seven Japanese male members of the general public, seven female members of the
      general public and seven physicians participated. RESULTS: It was revealed that
      the lay public expressed diverse attitudes towards the use of archived
      information and samples without informed consent. Protecting a subject's privacy,
      maintaining confidentiality, and communicating the outcomes of studies to
      research subjects were regarded as essential preconditions if researchers were to
      have access to archived information and samples used for research without the
      specific informed consent of the subjects who provided the material. Although
      participating physicians thought that some kind of prior permission from subjects
      was desirable, they pointed out the difficulties involved in obtaining individual
      informed consent in each case. CONCLUSIONS: The present preliminary study
      indicates that the lay public and medical professionals may have different
      attitudes towards the use of archived information and samples without specific
      informed consent. This hypothesis, however, is derived from our focus groups
      interviews, and requires validation through research using a larger sample.

PMID- 11825346
TI  - Quality and methods of developing practice guidelines.
AB  - BACKGROUND: It is not known whether there are differences in the quality and
      recommendations between evidence-based (EB) and consensus-based (CB) guidelines.
      We used breast cancer guidelines as a case study to assess for these differences.
      METHODS: Five different instruments to evaluate the quality of guidelines were
      identified by a literature search. We also searched MEDLINE and the Internet to
      locate 8 breast cancer guidelines. These guidelines were classified in three
      categories: evidence based, consensus based and consensus based with no explicit
      consideration of evidence (CB-EB). Each guideline was evaluated by three of the
      authors using each of the instruments. For each guideline we assessed the
      agreement among 14 decision points which were selected from the NCCN (National
      Cancer Comprehensive Network) guidelines algorithm. For each decision point we
      recorded the level of the quality of the information used to support it. A
      regression analysis was performed to assess if the percentage of high quality
      evidence used in the guidelines development was related to the overall quality of
      the guidelines. RESULTS: Three guidelines were classified as EB, three as CB-EB
      and two as CB. The EB guidelines scored better than CB, with the CB-EB scoring in
      the middle among all instruments for guidelines quality assessment. No major
      disagreement in recommendations was detected among the guidelines regardless of
      the method used for development, but the EB guidelines had a better agreement
      with the benchmark guideline for any decision point. When the source of evidence
      used to support decision were of high quality, we found a higher level of full
      agreement among the guidelines' recommendations. Up to 94% of variation in the
      quality score among guidelines could be explained by the quality of evidence used
      for guidelines development. CONCLUSION: EB guidelines have a better quality than
      CB guidelines and CB-EB guidelines. Explicit use of high quality evidence can
      lead to a better agreement among recommendations. However, no major disagreement
      among guidelines was noted regardless of the method for their development.

PMID- 11825347
TI  - Resource use data by patient report or hospital records: do they agree?
AB  - BACKGROUND: Economic evaluations alongside clinical trials are becoming
      increasingly common. Cost data are often collected through the use of postal
      questionnaires; however, the accuracy of this method is uncertain. We compared
      postal questionnaires with hospital records for collecting data on physiotherapy
      service use. METHODS: As part of a randomised trial of orthopaedic medicine
      compared with orthopaedic surgery we collected physiotherapy use data on a group
      of patients from retrospective postal questionnaires and from hospital records.
      RESULTS: 315 patients were referred for physiotherapy. Hospital data on
      attendances was available for 30% (n = 96), compared with 48% (n = 150) of
      patients completing questionnaire data (95% Cl for difference = 10% to 24%); 19%
      (n = 59) had data available from both sources. The two methods produced an
      intraclass correlation coefficient of 0.54 (95% Cl 0.31 to 0.70). However, the
      two methods produced significantly different estimates of resource use with
      patient self report recalling a mean of 1.3 extra visits (95% Cl 0.4 to 2.2)
      compared with hospital records. CONCLUSIONS: Using questionnaires in this study
      produced data on a greater number of patients compared with examination of
      hospital records. However, the two data sources did differ in the quantity of
      physiotherapy used and this should be taken into account in any analysis.

PMID- 11825349
TI  - [Retrocaval ureter].
AB  - OBJECTIVE: To improve the diagnosis of retrocaval ureter. METHOD: 20 cases of
      retrocaval ureter with an average age of 33.4 years were reported. The diagnosis
      of this disease depends on urography and retrograde ureterography. Operation was
      the principal treatment. Ureter orthopedics and reduction were performed in 19
      cases of type 1 (low loop) except one case of type II (high loop). After removing
      3 - 4 cm retrocaval ureter with pathological changes, we anastomosed the ureter
      without tension and regained its normal anatomic position. RESULT: B-ultrasound
      and excretory urography showed no stenosis and improvement of hydronephrosis.
      CONCLUSION: Ureter orthopedics and reduction are ideal for the treatment of
      retrocaval ureter.

PMID- 11825348
TI  - [Surgical treatment of epispadias].
AB  - OBJECTIVE: To analyse the surgical treatment of 124 cases of epispadias
      (incomplete 27 cases, complete 21 and complex 76). METHOD: Leadbetter's operation
      was used for anti-incontinence. Urethral tightening was used in 4 cases of
      complete female epispadias. Penile straightening was adopted for incomplete
      epispadias and penile lengthening for complete and complex male epispadias.
      RESULT: In 97 cases of urinary incontinence, complete continence was achieved in
      73. CONCLUSION: The orthopedic effects of external genitals were satisfactory.

PMID- 11825350
TI  - [Primary epididymal tumors].
AB  - OBJECTIVE: To improve the diagnosis of primary epididymal tumors. METHOD: In 23
      primary epididymal tumors (22 benign and 1 malignant), 14 were adenomatoid
      tumors, 6 were leiomyomas, 1 was multiple fibrous pseudomonas and 1 was
      sclerosing hemangioma. Epididymal adenocarcinoma was seen in a 57-year-old man.
      RESULT: Epididymal tumors might be easily misdiagnosed as epididymal
      tuberculosis, chronic epididymis and spermatocele. Apart from certain benign
      clinical characteristics, benign epididymal tumors could be diagnosed by B
      ultrasonography and aspiration biopsy. Most malignant tumors of epididymis
      presented as rapidly growing scrotal masses and cured by the removal of tumors or
      the whole epididymis of the same side. 19 of 22 cases were free from recurrence.
      CONCLUSION: Malignant epididymal tumors should be treated as malignant tumors of
      testis and their prognosis is extremely poor.

PMID- 11825351
TI  - [Low semi-cystectomy in treating trigone of bladder neck carcinoma].
AB  - OBJECTIVE: To resect the tumor in trigone and bladder neck and remain urination
      function. METHOD: A new procedure low segmental-cystectomy which includes
      resection of the trigone of bladder, prostate, seminal vesicles, extremity of
      ureter, was performed on 8 patients aged 28 to 57 years. RESULT: The patients
      were followed up for 6 months to 3 years. No recurrent tumor and metastasis were
      found, and urination function was normal. CONCLUSION: This procedure is superior
      to Bricker's operation, Kock pouch bladder and ileal neo-bladder. The patients
      enjoy good life quality after operation.

PMID- 11825352
TI  - [The use of laparoscopy in urology: report of 141 cases].
AB  - OBJECTIVE: To modify laparoscopy in urology. METHOD: From May 1992 to Nov. 1996,
      141 patients (110 males and 31 females) were subjected to laparoscopy in the
      treatment of urological diseases. The age of the patients ranged from 9 to 76
      years (mean 39 years). Five patients had nephrectomy, 12 adrenalectomy, 48 renal
      cyst resection, 61 high ligation of internal spermatic vein, 5 pelvic staging
      lymphadenectomy, 9 orchiectomy, and 1 removal of bladder diverticulum. RESULT:
      The rate of successful operation was 95.7% and that of complications was 2.22%.
      The mean hospitalization was 4.9 +/- 4.1 days. CONCLUSION: Laparoscopy can be
      used widely in clinical practice.

PMID- 11825353
TI  - [Retroperitoneal laparoscopic unroofing of renal cyst: use of close method].
AB  - OBJECTIVE: To study the close method of retroperitoneal laparoscopic unroofing of
      renal cyst. METHOD: A close method retroperitoneal laparoscopic unroofing of
      renal cyst was attempted in 35 cases between May 1995 and December 1996. The age
      of the patients ranged from 30 to 72 and the cyst size from 4.0 to 9.3 cm.
      RESULTS: The operative procedure took around 50 minutes. After a 1 - 18 month
      follow up, we observed the disappearance of all renal cysts. CONCLUSION: The
      laparoscopic procedure renders less trauma and discomfort to the patients and may
      be better indicated for symptomatic, simple renal cysts.

PMID- 11825354
TI  - [Timing of surgical treatment for gallstone pancreatitis].
AB  - OBJECTIVE: To evaluate the timing of surgery in the treatment of gallstone
      pancreatitis (GP). METHOD: The records of 53 patients with GP were
      retrospectively analysed. RESULT: The morbidity and mortality of early surgical
      treatment (less than 48 hours after admission) were 29.20% and 9.30%,
      respectively, in contrast to 3.50% and 0 in patients who underwent delayed
      surgical treatment (more than 48 hours after admission) (P < 0.05). In mild
      gallstone pancreatitis (APACHE-II <or= 8), timing of surgery appeared to have
      little effect on outcome. However, the rates of common bile duct exploration and
      the morbidity were 91.70% and 11.10% in the patients receiving early surgery,
      significantly higher than those (62.10% and 0) in the patients receiving delayed
      surgery. In severe gallstone pancreatitis patients (APACHE-II > 8), the timing of
      surgery was related to the morbidity and mortality, namely, they were higher in
      early surgery than in delayed surgery. CONCLUSION: We suggest delayed surgical
      treatment for mild gallstone pancreatitis, and delayed and selective surgery for
      severe gallstone pancreatitis.

PMID- 11825355
TI  - [Diagnosis and treatment of primary hyperparathyroidism].
AB  - OBJECTIVE: To study the diagnosis and treatment of hyperparathyroidism. METHOD:
      37 patients with primary hyperparathyroidism (PHPT) were confirmed
      pathologically. The course of the disease varied, the longest one being 14 years
      and the shortest one 3 months. RESULT: 35 patients had parathyroid adenoma, 1
      hyperplasia of parathyroid, and 1 carcinoma of parathyroid. The main clinical
      manifestation was symmetrical pain of the supporting bones and joints,
      hypercalcemia, hypercalcinuria, hypophosphatemia, hyper-alkaline phosphatasemia,
      and increase of iPTH in peripheral blood. X-ray examination showed osteoporosis
      and decalcification, accompanied with multiple fracture occasionally, we injected
      (99m)Tc and MiBi into inferior thyroid artery as a demonstration for the
      diagnosis of tumor of parathyroid. CONCLUSION: The key procedure of the operation
      was to search for tumor of parathyroid. We used thymus-thyroid ligament as guide
      and injected methylene blue into the artery during operation to search thyroid.

PMID- 11825356
TI  - [Primitive neuroectodermal tumor of bone and soft tissue].
AB  - OBJECTIVE: To study the pathological characteristics of primitive neuroectodermal
      tumor (PNET) of bone and soft tissue. METHOD: Five patients with bone and soft
      tissue of PNET (2 men and 3 women) were studied by light microscope and
      immunohistochemistry. The age of the patients was 18, 18, 43, 14, 32 years and
      the primary sites of involvement were the ilium (n = 2), axillary fossa (n = 1),
      condyle of femur (n = 1), and diploe (n = 1). X-ray films showed bone osteolytic
      destruction, and no periosteal reaction or calcification. Surgery was performed
      in the patients. RESULT: All patients received combined chemotherapy and 3
      received radiotherapy. Three patients died of metastatic tumor of lung 20, 13,
      and 5 months after invasion. 1 patient metastatic tumor of lung 20 months after
      invasion, and 1 patient bone extensive metastasis 1.5 months after surgery.
      CONCLUSION: The treatment of PNET of bone and soft tissue awaits further study.

PMID- 11825357
TI  - [Lung autotransplantation technique in the treatment of stage III bronchogenic
      carcinoma].
AB  - OBJECTIVE: To perform a double sleeve right upper and middle bilobectomy with
      transposing the inferior pulmonary vein to the superior one stump in a lung
      cancer patient. METHOD: The "cut-down" lobe was immersed in heparin solution in
      vitro for 15 minutes. It took 15, 14 and 10 minutes to finish the anastomosis of
      pulmonary vein, bronchus, and artery. The pulmonary artery was blocked for 3
      hours. Postoperatively, the patient underwent ventilation for 6 hours. RESULT: In
      the 5th day after operation, re-implanted lung inflated well, the chest tube was
      retreated, and the patient can walk around. The reconstruction of pulmonary
      vessels and airway was done by spiral CT, which demonstrated no stenoses of
      bronchi and the pulmonary blood perfused and returned very well 3 weeks after
      operation. Follow-up more than 6 months showed the patient had a good quality of
      life and resumed his work. CONCLUSION: It is indicated to apply the technique of
      lung autotransplantation for operation on the central bronchogenic carcinoma when
      the main bronchus or pulmonary artery involved by tumor is too long to perform
      the anastomosis in the double sleeve bilobectomy.

PMID- 11825358
TI  - [The relationship between nm23-H1 loss of heterozygosity and metastasis in
      hepatocellular carcinoma].
AB  - OBJECTIVE: To demonstrate the relationship between nm23-H1 loss of heterozygosity
      (LOH) and clinical pathological characteristics of hepatocellular carcinoma (HCC)
      from the DNA level. METHOD: Southern blot hybridization was used to analyze
      genomic DNA in liver cancer and its corresponding liver tissue. RESULT: nm23-H1
      has diallelic bands at 7.6 Kb and 2.3 Kb. Allelic loss of heterozygosity in
      tumour tissues was detected in 31.25% patients (5 patients). LOHs were more
      common in the tumours with intrahepatic metastasis or portal vein tumour embolism
      and the tumours poorly differentiated (Edmondson's classification III, IV).
      CONCLUSION: nm23-H1 LOHs may induce the metastasis potential of HCC and help to
      predict recurrence and metastasis of HCC.

PMID- 11825359
TI  - [PCR in detecting the correlation between infection of HBV and cholelithiasis].
AB  - OBJECTIVE: To study the correlation between cholelithiasis and the infection of
      HBV. METHOD: 32 formalin-fixed and paraffin-embedded gallbladder samples of
      cholelithiasis patients and 20 gallbladder samples of non-cholelithiasis patients
      were investigated using the polymerase chain reaction-Ethidium bromide (PCR-EB)
      assay. The 52 patients were positive to HBV serologic markers. RESULT: The
      results showed that HBV-DNA was found in 13 gallbladder samples of 32
      cholelithiasis patients (40.63%), significantly higher than that in 3 gallbladder
      samples of 20 non-cholelithiasis patients (15%). CONCLUSION: The infection of HBV
      and the formation of cholelithiasis are correlated.

PMID- 11825360
TI  - [Radionuclide pulmonary perfusion imaging in evaluating pulmonary hypertension in
      patients with congenital heart disease].
AB  - OBJECTIVE: To evaluate the degree of pulmonary hypertension in patients with
      congenital heart disease (CHD) by using radionuclide pulmonary perfusion imaging.
      METHOD: The pulmonary perfusion in 81 patients with left to right cardiac shunts
      was examined by scintigram with macroaggregates of (99m)Tc-labeled human serum
      albumin (PPS). PPS was analyzed for (1) lung regional radionuclide count (LRC),
      (2) right upper and lower lung count ratio (RULR), (3) kidney count ratio (KCR).
      The results were compared with those of cardiac catheterization exam. RESULT:
      There were correlation between mean pulmonary arterial pressure (mPAP), total
      pulmonary resistance (TPR), and PPS (KCR, RULR with mPAP gamma = 0.25, 0.35; LRC,
      KCR with TPR gamma = -0.34, 0.29). Five patients repeated PPS test after early
      operation. There were no changes in PPS. CONCLUSION: The degree of reversibility
      of pulmonary hypertension in patients with CHD could be quantitatively analysed
      by PPS.

PMID- 11825361
TI  - [Fate of massive retrieved human bone allografts].
AB  - OBJECTIVES: To study retrieved massive human allograft specimen after they had
      been in situ for four to sixty-five months, and to investigate the changes union,
      bone replacement and degradation of articular cartilage. METHOD: BMP gene
      expression in the specimen was also studied with in situ hybridization,
      immunohistochemical methods, and the observations were correlated with the
      clinical and isotope scan date. RESULT: The union between the allograft and the
      host was achieved by the formation of an external callus derived from the cortex
      of the host. New bone replacement took place slowly. Analysis of the articular
      cartilage revealed evidence that some chondrocytes had survived in non bearing
      area of the articular. The expression of BMP in the surface of the cortex and
      united callus was positive 4 months after implantation. But it was negative in
      the center of cortex after it had been implanted for over 12 months. An external
      callus formed from the cortex of the host. Some chondrocytes survived in non
      bearing area of the articular. Neovasculature penetrated into osteoarticular.
      CONCLUSION: Bone absorption may be the cause of collapse of articular surface.
      The results suggest that large allografts in humans are osteo-conductive rather
      than inductive. Incomplete repair of osteon may be related to slowed replacement
      of massive human allograft.

PMID- 11825362
TI  - [Fatal complications in traffic accident injury].
AB  - OBJECTIVE: To discuss the relative factor, development tendency and prevention of
      the fatal complications in traffic accident injury. METHOD: We observed injury
      severity scale (AIS-ISS), clinical response time, and occurrence in traffic
      accident injury with fatal complications. Ridit mathematical statistics and Q
      test were used. RESULT: There were high ISS and long clinical response time in
      traffic accident injury with fatal complications. A significant relation was
      found between complications and the progress of time after trauma, thereby the
      clinical course could be divided into phases of cerebral hernia and shock (or
      acute), transition, infection and multiple organ dysfunction syndrome (MODS).
      There was higher head AIS in the cerebral hernia. ISS of shock patients was
      significantly higher than that of the others. Massive infections occurred in the
      patients with extremity trauma. There was a significant relation between the
      occurrence of MODS and infection. CONCLUSION: The occurrence of fatal
      complications is related to the location and severity of injury in traffic
      accident injury. A regularity is present in the occurrence of fatal complications
      with time progress.

PMID- 11825363
TI  - [The relationship of facet orientation to intervertebral disc protrusion and
      lateral recess stenosis in lower lumbar spine].
AB  - OBJECTIVE: To investigate the relationship of facet orientation to intervertebral
      disc protrusion and lateral recess stenosis in lower lumbar spine. METHOD: The
      relationship between facet geometry (joint angle and tropism) and disc
      protrusion, lateral recess stenosis was investigated with computer tomography
      (CT) at the vertebral levels L(3 - 4), L(4 - 5), and L(5) - S(1). 772 facet joint
      angles (386 lower lumbar levels of 136 patients) were measured on coronal CT
      scans by transverse inter-facet angle (TIFA). RESULT: There was no statistically
      significant relationship between facet joint asymmetry and disc protrusion (P >
      0.05). Disc protrusion occurred more frequently on side of sagittally oriented
      facet joint than coronal side (P < 0.01). The patients whose lumbar transverse
      inter-facet angle less than 20 degrees easily suffered from degenerative lumbar
      lateral recess stenosis in the elderly. The TIFA in Asian less evident than in
      European may be the important cause for high incidence of lumbar lateral recess
      syndrome in Asia. CONCLUSION: Stress on the lower lumbar spine leads to disc
      protrusion. No association is found between facet joint asymmetry and lumbar disc
      protrusion. The asymmetry of facet joint will influence the direction of
      intervertebral disc protrusion at level from L(4) - S(1). The patient whose lower
      lumbar spine inter-facet angle may unlikely suffer from degenerative lumbar
      lateral recess stenosis.

PMID- 11825364
TI  - [The influence of intrahepatic transplantation of hepatocytes and insular cells
      on liver cirrhosis].
AB  - OBJECTIVE: To protect liver function, we used the cirrhotic rats to study whether
      the postshunt intrahepatic transplantation of hepatocytes and insular cells via
      hepatic artery can improve liver function. METHOD: We irrigated the cirrhotic
      liver of rat via hepatic artery with hepatocytes and insular cells and observed
      the influence of this method on liver function. RESULT: The improvement of TP,
      ALB and TBIL in the experimental group were significant, and there was
      significant difference in these parameters between the experimental and control
      groups (P < 0.01). Light microscopic examination of liver fibrosis and
      immunohistochemistry and data analysis of I, II collagens also showed significant
      difference (P < 0.05). CONCLUSION: The intrahepatic transplantation of
      hepatocytes and insular cells via hepatic artery can not only improve liver
      function, but also increase the degradation of liver collagens and reverse the
      course of liver cirrhosis.

PMID- 11825365
TI  - [The role of nitric oxide in hyperdynamic circulation in portal hypertensive
      rats].
AB  - OBJECTIVE: To evaluate the role of nitric oxide (NO) in hyper-hemodynamics in
      portal hypertension, we investigated the effects of nitric oxide synthase
      inhibitor L-NMMA with or without L-arginine, the substrate for enzyme NO synthase
      on the systemic and splanchnic hemodynamics in portal hypertensive rats. METHOD:
      Ninety-seven male Sprague-Dawley rats were divided into four groups: intrahepatic
      portal hypertension (IHPH, n = 23) by injection of CCl4, prehepatic portal
      hypertension (PHPH, n = 26) by stenosis of the portal vein, end-to-side
      portacaval shunt (PCS, n = 23), and sham-operated controls (SO, n = 25). Animals
      of each group were divided into three subgroups: systemic administration of L
      NMMA (50 mg/kg BW, 1 ml), L-NMMA (50 mg/kg BW, 0.5 ml) plus L-arginine (30 mg/kg
      BW, 0.5 ml), and normal saline solution (1 ml). The radioactive microsphere
      method was used for hemodynamic study. RESULT: There was the characteristic of
      hyperdynamic circulatory state including increased cardiac output and splanchnic
      blood flow, decreased mean arterial blood pressure, total peripheral vascular
      resistance and splanchnic vascular resistance in IHPH, PHPH and PCS rats. The
      hyperdynamic circulatory state in IHPH, PHPH and PCS rats could be effectively
      reversed by L-NMMA to the resting values of hemodynamics in SO rats, but not the
      levels after administration of L-NMMA in SO rats, indicating that there is
      excessive production of NO in portal hypertensive and PCS rats. Administration of
      L-arginine counterbalanced the effects of L-NMMA on hyperdynamic circulatory
      state in portal hypertensive and PCS rats. CONCLUSION: NO is an important
      mediator of hyperdynamic circulation in portal hypertension.

PMID- 11825366
TI  - [Living related liver transplantation: a case report].
AB  - OBJECTIVE: To study a case of living related liver transplantation. METHOD: The
      patient was a 10-year-old girl who suffered from congenital diffuse intrahepatic
      cholangiectasis, recurrent cholangitis and hepatocirrhosis. The donor was the
      patient's father aged 40. The left lateral lobe of donor's liver was cut and
      grafted to the patient. Intensive care and treatment as well as follow-up were
      given after operation. RESULT: For the donor, the operation lasted 400 min, with
      410 ml bleeding and 300 g liver removed. The recovery was satisfactory. For the
      recipient, the operation lasted 652 min, with 1665 ml bleeding, 80 min non-liver
      stage, 0 min graft hot ischemic stage, and 137 min cold ischemic stage.
      Immunosuppressive therapy was given using cyclosporin A, azathioprine and
      adrenocortical hormones. There was an acute rejection 11 days after operation,
      which was controlled using hormone impulsive therapy. The patient has been
      surviving 7 months with normal liver function. CONCLUSION: The living related
      liver transplantation is feasible under modern surgical conditions. It is
      demonstrated that perfect postoperative management is the key for the successful
      liver transplantation.

PMID- 11825367
TI  - [90Y glass microspheres intraradiopraxis of advanced hepatic carcinoma].
AB  - OBJECTIVE: To evaluate intraradiopraxis with (90)Y glass microspheres for
      advanced hepatic carcinoma. METHOD: 28 patients were divided into two group: A
      treated by (90)Y and hepatic artery embolism and chemotherapy (HAEC) (n = 13),
      and B by (90)Y and hepatic artery embolism (HAE) (n = 15), and 15 cases (group C)
      only treated by HACE simultaneously were used as controls. The average age,
      course, and diameter of tumor were similar in all groups (P > 0.05). RESULT: The
      effective rate of the group A and B was 61.5% and 66.6% respectively, and that of
      the group C was only 33.3% (P < 0.001). The average survival time of the group A
      and B was 9.86 and 11.9 months respectively, and that of the group C was only 4.5
      months (P < 0.001). CONCLUSION: The intraradiopraxis with (90)Y glass microsphere
      would be a valuable method for patients with hypo-leukocyte count, insensitive to
      chemotherapy or resistant to chemotherapy.

PMID- 11825368
TI  - [Hepatectomy for hepatolithiasis treatment of 354 cases].
AB  - OBJECTIVE: To evaluate the effect of hepatectomy for hepatolithiasis. METHOD: 354
      patients with hepatolithiasis underwent hepatectomy in the past 10 years. The
      results were analysed retrospectively, including clinical findings, distribution
      of stones, patterns of operation, postoperative complications, and residual
      stones. The clinical data of the patients before 1990 were compared with those
      thereafter. RESULT: Left hepatolithiasis was the most common form (323 patients).
      Left lateral lobectomy and left hepatectomy were most commonly employed (91.2%).
      166 of the patients underwent concurrent cholangiojejunostomy. 13.8% patients had
      residual stones, and postoperative complications occurred in 60 patients,
      including 4 deaths. Few patients were reoperated on and the incidence of residual
      stones was lower after 1990. 88% the patients showed excellent or good result.
      CONCLUSION: Hepatectomy is a procedure for the management of hepatolithiasis, but
      still requires combined plasty of stenotic intrahepatic bile ducts and
      cholangiojejunostomy to reduce the incidence of residual stones and recurrence.

PMID- 11825369
TI  - [Endovascular exclusion of abdominal aortic aneurysm].
AB  - OBJECTIVE: To explore the indications, methods, manipulations, and problems of
      endovascular exclusion of abdominal aortic aneurysm (AAA). METHOD: Under general
      anesthesia and dynamic supervision of DSA, an endovascular exclusion with a stent
      graft complex of 11.0 cm x 2.6 cm was successfully performed on a 70-year-old man
      contraindicated for major open surgery with AAA of 10.0 cm x 6.0 cm and an AAA
      neck of 2.5 cm x 1.6 cm. RESULT: The patient was up and about on the first
      postoperative day. Duplex scan (by the end of the first postoperative week) and
      CT (on the postoperative 20th day) revealed a completely excluded AAA by the
      stent-graft that was patent and had an inner diameter of 2.2-2.4 cm, without
      migration and torsion. The primary AAA sac was full of thrombi and no patent
      lumbar and inferior mesenteric arteries were observed. The external diameter of
      AAA was unchanged, renal and iliac arteries were all patent, but a micro-crevice
      between the proximal end of the stent-graft and the anterior wall of the AAA neck
      was revealed. Six months postoperative follow-up showed that the patient's
      abdominal pulsatile mass and the left lower extremity's claudication disappeared.
      CONCLUSION: Endovascular exclusion of AAA is of great practical value.

PMID- 11825370
TI  - [The timing and mode of surgery in patients with severe acute pancreatitis].
AB  - OBJECTIVE: To investigate the timing and mode of surgical management in patients
      with severe acute pancreatitis (SAP). METHOD: The timing, mode of operation and
      mortality were reviewed retrospectively in 50 SAP cases undergoing laparotomy in
      our hospital from 1985 to 1994. RESULT: The overall mortality was 14% and 85.7%
      of the mortality falls on the age between 40 to 60 years, with no difference in
      etiology and sex. The operative mortality reduced gradually in patients with
      longer duration of illness (P > 0.05). The operative mortality of 31.8% in
      patients undergoing laparotomy within 12 h after hospitalization was
      significantly higher (P < 0.05) than in these operated on later. When the number
      of injured extra-pancreatic organs increased, the mortality also increased
      significantly (chi(2) = 5.99, P < 0.05). The related mortality with shock,
      pancreatic necrosis and multiorgan failure (MOF) was 31.8%, 31.6% and 28%,
      respectively (P < 0.05). The main procedures of surgical management were
      pancreatic debridement and/or drainage, and combined surgical measures.
      CONCLUSION: The laparotomy timing is an important factor influencing mortality as
      well as the severity of pancreatic necrosis, sepsis, and MOF. Delayed laparotomy
      and 24 h preoperative management is recommended. Surgery adopted should be
      simple, efficient in drainage and debridement.

PMID- 11825371
TI  - [Reoperation for recurrent carcinoma of the esophagus and cardia].
AB  - OBJECTIVE: To review the experience of reoperation for recurrent carcinoma of the
      esophagus and cardia. METHOD: Between 1979 and 1996, 44 patients with recurrent
      esophageal and cardiac cancer after the first operation underwent reoperation.
      Among them, 21 had esophageal cancer and 23 cardiac cancer. 36 patients were male
      and 8 female, with age ranged from 42 to 68 years. RESULT: The resectability rate
      was 77.2% (34/44) and the hospital mortality rate was 5.8%. Postoperative
      complications occurred in 7 patients with a morbidity of 20.5%. Pathologically,
      previous anastomotic relapse was seen in 26 patients, recurrent lesion of
      residual esophagus in 7, and recurrent cancerous residue at the esophageal bed in
      1. 15 patients (44%) showed lymph node metastasis. Follow-up showed that 4
      patients survived for 5 years, 4 for 3 years, and 3 for 2 years. 15 patients died
      within one year after reoperation. CONCLUSION: The recurrence of esophageal and
      cardiac cancer after first operation is not a contraindication to reoperation,
      but careful preoperative assessment and patients' selection should become an
      integral part of the evaluation of these patients.

PMID- 11825372
TI  - [Reoperative treatment of recurrent retroperitoneal tumor].
AB  - OBJECTIVE: To improve the resection rate and survival rate for recurrent
      retroperitoneal tumor (RRT). METHOD: We analysed 34 patients with RRT who were
      treated in our hospital from 1987 to 1995. One patient had benign tumor, the
      others malignant. Because 7 patients were operated on over one time, we performed
      53 operations including complete resection in 42 patients, palliative resection 8
      and biopsy 3. RESULT: The 1-and 2-year survival rates for complete resection
      cases were 71.2% and 65.3%. The patients who received palliative resection and
      biopsy died within one year. CONCLUSION: The diagnosis, preoperative preparation
      and intraoperative management of RRT are important to operative safety and
      survival rate. We emphasize the importance of reoperation and complete resection
      for RRT.

PMID- 11825374
TI  - [Virilizing and feminizing adrenal syndrome].
AB  - OBJECTIVE: To inquire into diagnosis, differential diagnosis and treatment of
      virilizing and feminizing adrenal syndrome especially differential diagnosis
      between benign and malignant of sex hormone producing adrenal neoplasma and
      treatment principles of congenital adrenal hyperplasia (CAH). METHOD: Eight cases
      of CAH and five cases of sex hormone producing adrenal neoplasma were presented
      during 1986-1996. The former included 3 rare cases of 17 alpha hydroxylase
      deficiency and others. The latter included 3 cases of feminizing adrenal tumors
      and 2 cases of virilizing adrenal tumors. RESULT: Weight and diameter of tumor,
      DHEA, 17-ks and sex hormone levels, appearance of CT imaging, infiltration and
      metastasis, were closely related to differentiation of benign and malignant
      tumors. CONCLUSION: Some standards are not absolute because of limited practice,
      follow-up is very important. Adrenal virilizing and feminizing neoplasms were
      surgically resected by different incision. Modified subcostal incision is
      recommended as a best choice for huge adrenal mass. Corticoadrenal hormone
      treatment of CAH should select different kind of corticoadrenal medicine for
      different kind of CAH. Treatment of sex hormones is not suitable for children
      suffered from 17 hydroxylase deficiency until prepuberty.

PMID- 11825373
TI  - [Cervical spondylotic myelopathy: early diagnosis and timing of operation].
AB  - OBJECTIVES: To study early clinical characteristics and diagnosis of cervical
      spondylotic myelopathy and to search the timing of surgery. METHOD: Seventy-four
      cases of early diagnosed cervical spondylotic myelopathy (CSM) were treated with
      anterior cervical decompression and autologous ilium graft fusion. RESULT: The
      early stage of CSM was indistinct, and symptoms were mild. Neck pain, abnormality
      of motion and sensation of limbs, and hand and arm symptoms were shown
      frequently. Changes in neurological function could found during physical
      examination. Characteristic changes in imaging were helpful in early diagnosis of
      the disease. CONCLUSION: Early diagnosis and surgery of CSM are important in
      improving the therapeutic results.

PMID- 11825375
TI  - [The pathogenesis of infection complicated by acute necrotizing pancreatitis: an
      experimental study].
AB  - OBJECTIVE: To observe the injury of gut barrier function and intestinal bacterial
      translocation following acute necrotizing pancreatitis (ANP), and to investigate
      the pathogenesis of infection complicated by ANP. METHOD: Fifteen dogs were
      colonized with a strain of E. coli JM109 bearing ampicillin-resistant plasmid
      PUC18, then divided into two groups: control group (n = 7) and ANP group (n = 8).
      Acute necrotizing pancreatitis was induced by injection of sodium taurocholate
      and trypsin into the pancreatic duct. RESULT: In the ANP group, as compared with
      the control group, serum amylase level increased significantly, the
      lactulose/mannitol ratio was 2-12 times higher, blood and ileum diamine oxidase
      activity decreased significantly. E. coli population in intestinal mucosal flora
      increased, while bifidobacterium and lactobacillus reduced significantly.
      Bifidobacterium/E. coli ratio was reversed. Morphological study revealed areas of
      hemorrhage and necrosis in the pancreas and shedding of ileal villi. In the
      control group, blood cultures were negative, and no organism was found in organs
      except for mesenteric lymph nodes in two dogs. In the ANP group, blood and organ
      cultures were positive in all dogs and JM109 could be found uniformly too.
      CONCLUSION: ANP impaired the gut barrier function, which led to bacterial
      translocation from the gut to the pancreas and other organs, serving as a primary
      source of infection secondary to ANP.

PMID- 11825376
TI  - [A monoclonal antibody that reacts with an antigen on both normal and malignant
      prostate cells].
AB  - OBJECTIVE: To study the YDPC--a monoclonal antibody that reacts with an antigen
      on both normal and malignant prostate cell. METHOD: A murine monoclonal antibody
      (MAb) designated YDPC was generated by treating the primed spleen cells with
      leucine methyl ester (LeuOMe) following immunization of mice with prostate cancer
      cell line PC-3M. RESULT: YDPC reacted uniformly with all adenocarcinomas of the
      prostate examined. It also reacted with the surface antigen on normal prostate
      epithelial cells and on cells from benign prostate hyperplasia. YDPC reacted with
      a limited number of normal tissues including renal tubules, adrenal and sweat
      gland. In addition, three lymph nodes metastasis and one bladder metastasis were
      found to be strongly positive, while four transitional cell carcinomas of the
      prostate negative. Preliminary experiments showed that this antibody does
      specifically localize to prostate cancer xenografts in nude mice. CONCLUSION:
      YDPC reacts with a differentiation antigen and this antigen continues to be
      expressed on all adenocarcinomas of the prostate. This antibody may be useful in
      the diagnosis of or therapy for prostate cancer.

PMID- 11825377
TI  - [Exfoliative cancer cells in the surgical field of breast cancer].
AB  - OBJECTIVE: To study the relationship between exfoliative cancer cells in the
      surgical field and pathological stages of breast cancer and provide a theoretical
      basis for killing or removing of the exfoliative cancer cells in the surgical
      field. METHOD: Cytological examination of surgical field washings was performed
      in 104 patients with breast cancer. The results and pathological stages were
      compared and analysed. RESULT: Exfoliative cancer cells were found in the
      surgical field washings in 36 of 104 (34.6%). Stage I, II and III showed a
      positive rate of 3.8%, 29.8% and 85.7%. The positive rate of T(1), T(2) and
      beyond T(3) were 10.8%, 33.3% and 77.3%, respectively. When the number of
      axillary metastatic lymph nodes was over four, the positive rate of exfoliative
      cancer cell was 76.0% and only 13.5% if no axillary lymph node metastasis.
      CONCLUSION: Killing or removing of the exfoliative cancer cells in the surgical
      field of breast cancer is necessary.

PMID- 11825378
TI  - [Distribution of B-lymphocyte subgroup CD20 and its clinical significance in
      patients with myasthenia gravis].
AB  - OBJECTIVE: To assess the distribution and clinical significance of B-lymphocyte
      subgroup CD20 in patients with myasthenia gravis. METHOD: B-lymphocyte subset
      CD20 was studied in patients with thymomas associated with or without myasthenia
      gravis using immunohistochemistry technique. RESULT: The moderate and obvious
      aggregation of CD20 positive cells was found in patients with myasthenia gravis,
      there was a significant difference when compared with those patients without
      myasthenia gravis (chi(2) = 26.032, P < 0.01). There was negative correlation
      between the distribution of CD20 positive cells and the staging of thymomas
      (gamma = 0.07), and no correlation between the distribution and clinical type of
      myasthenia gravis (gamma < 0.4). CONCLUSION: The results of this study indicated
      that pathological changes of thymus are more important than those of thymomas
      itself in the pathogenesis of myasthenia gravis. The degree of B-lymphocyte
      subgroup aggregation can not truly reflect clinical status because of the
      heterogeneity of antibody against acetylcholine receptor.

PMID- 11825380
TI  - [Pathological study of ER and PR in osteosarcoma].
AB  - OBJECTIVE: To determine the relationship between estrogen receptor (ER),
      progesterone receptor (PR) and pathological characteristics of osteosarcoma.
      METHOD: ER and PR were detected by streptavidin/peroxidase (SP) method
      immunohistochemically using the paraffin embedded tissues from 65 cases of
      osteosarcoma. The patients were typed and graded pathologically according to Liu
      Zijun's classification. RESULT: The positive rates of ER and PR were 40% (26/65),
      32.3% (21/65) respectively. The positive particles were distributed in cytoplasm
      and nucleus. The positive rates of ER and PR in osteosarcoma with higher cell
      differentiation grade were higher than those in the tumor with lower one. The
      differences were statistically significant (P < 0.05). There were no relations to
      the pathological type. CONCLUSION: ER and PR exist in osteosarcoma and their
      positive rates are related to the cell differentiation of osteosarcoma.

PMID- 11825379
TI  - [The distribution of nerve endings in the human cervical nerve roots].
AB  - OBJECTIVE: To find out the distribution of nerve endings in the dural sheath of
      cervical nerve roots and to study the mechanism of cervical radicular pain.
      METHOD: 2069 20 microm serial sections were made from 39 cervical root-dorsal
      root ganglion specimens obtained from 18 postmortems. By using optical microscope
      and Suzuki silver impregnation method and Kluver-Brrera method, we examined the
      morphology, quantity and distribution of the nerve ending in the nerve sheath of
      the root, dorsal root ganglion (DRG) and the spinal nerve of these sections.
      RESULT: There were several kinds of nerve endings such as free nerve endings in
      the nerve sheath of the root, the dorsal root ganglion, and the spinal nerve.
      Free nerve endings were distributed in the proximal and distal portions of DRG
      sheath more extensive than that in other parts of the dural root-sheaths.
      CONCLUSION: The free nerve endings in the dural root-sheaths especially those in
      the DRG sheath are thought to play an important role in cervical radicular pain.

PMID- 11825381
TI  - [Mechanism of preventing the recurrence of bladder carcinoma by intravesical
      instillation of BCG plus IL-2].
AB  - OBJECTIVE: To study the mechanism of preventing the recurrence of bladder
      carcinoma by intravesical instillation of BCG plus IL-2. METHOD: Intravesical
      instillation of BCG or BCG plus IL-2 were carried out in the bladder transitional
      cell carcinoma patients undergoing surgical operation (16, 19 cases
      respectively). RESULT: They were followed up for 14-22 months. The recurrence
      rates were 31.25% and 21.05% respectively. At 6 weeks after the instillation of
      IL-2 plus BCG, the peripheral blood NKCF activity was increased significantly and
      there was a significant positive correlation between the activities of NKCF and
      IL-2. CONCLUSION: The intravesical instillation of IL-2 plus BCG is clearly
      superior to only BCG in preventing recurrence of bladder carcinoma. There may be
      immuno-enhancement and immuno-synergism.

PMID- 11825382
TI  - [Treatment of old femoral neck fracture with implantation of a vascularized
      fibular graft].
AB  - OBJECTIVE: To investigate the healing of old femoral neck fracture treated with
      transplantation of vascularized fibula graft accompanied with lag screw, and
      rehabilitation of and precaution against ischemic necrosis of femoral head.
      METHOD: Vascularized fibula autograft was transplanted to the anterolateral side
      of the femoral neck with an internal fixator of lag screw. Fibular artery and
      vein were anastomosed with lateral circumflex artery and vein. RESULT: 186 of 229
      cases subjected to systemic X-ray films and function follow-up (3 to 15 years).
      The percentage of fracture healing was 93.0% the sulass rate 86.5%. CONCLUSION:
      Fibula with blood supply and compressed screw have a combined fixation effect of
      the old femoral neck fracture. Fibula is solid enough for supporting the femoral
      head and preventing it from collapse. Vascularized fibular grafting provides
      blood supply to the affected femoral head and neck, promoting femoral head
      restoration and reconstruction.

PMID- 11825383
TI  - [Operative treatment of tibial condylar fracture].
AB  - OBJECTIVE: To analyse operative treatment of fresh and closed tibial condylar
      fractures. METHOD: In 92 patients (93 fractures) 87 were followed-up for 12-36
      months (average 18.6 months). A rasmussen's 30-point knee rating system was used.
      RESULT: 74 patients showed (84%) excellent results, 7 (8%) good and 7 (8%) poor.
      The success rate was 92%. CONCLUSION: To ensure excellent clinical results proper
      internal fixation should be based on (1) anatomic reduction; (2) adequate rigid
      internal fixation with screws or buttress plate(s) or both, and bi-condylar
      fixation if necessary; (3) bone grafting on all depressed areas; (4) early knee
      mobilization using CPM after the operation and avoiding external plaster
      fixation.

PMID- 11825384
TI  - [Misdiagnosis of tired fracture of distal segment of femur].
AB  - OBJECTIVE: To improve the diagnosis of tired fracture of the distal segment of
      femur, and to avoid its misdiagnosis. METHOD: Misdiagnosis of 5 patients with
      tired fracture of distal segment of the femur was reviewed. RESULT: Five male
      patients, aged 18 to 23 years had the lesion for 3 to 6 weeks. They had long
      tough experience of sports. The lesion was considered at first as osteosarcoma by
      radiograph and biopsy. It was eventually diagnosed as tired fracture of distal
      segment of the femur. Symptoms were relieved or disappeared after proper
      treatment. Follow-up for 7 to 18 months showed good results. CONCLUSION: The key
      to avoid misdiagnosis and mistreatment of the fracture is to know its causes,
      morphological features of fracture healing, and correct pathologic diagnosis.

PMID- 11825385
TI  - [Clinical diagnosis of Colles fracture combined with dorsal subluxation of radial
      carpal joints].
AB  - OBJECTIVE: To study the criteria for evaluating Colles fracture combined with
      dorsal radiocarpal subluxation (DRS). METHOD: Fifty cases of Colles fracture
      combined with DRS, 100 cases of simple Colles fracture without DRS, and 100
      normal wrist joint controls were included. We analysed central point displacement
      and perpendicular line ratio on the lateral view X-ray. For comminuted and
      severely displaced fracture, central point displacement (CPD) was not adopted
      because of difficulties in identifying the central point of the articular
      surface. Perpendicular line ratio (PLR) was suggested. RESULT: Prominent
      difference was seen in the CPDs and the PLRs between the Colles fracture combined
      with DRS group and the simple Colles fracture and the normal control group (P <
      0.01). Prominent relevance between the CPD and the PLR was also found (P < 0.05).
      CONCLUSION: Central point displacement and perpendicular line ratio can be
      regarded as the diagnostic criteria for Colles fracture combined with DRS. PLR is
      especially valuable when the central point is hard to be identified in very
      comminuted and severely displaced fractures. DRS is suggested when CPD is more
      than 2.5 mm and PLR is less than 0.76.

PMID- 11825386
TI  - [Incorporation of cortical allograft: a biomechanical study].
AB  - OBJECTIVE: To explore the changes of biomechanical properties of cortical
      allograft in different mechanical environments. METHOD: Cortical allograft was
      transplanted to each side of the midshaft diaphyseal ulnar of 40 rabbits. The
      left transplanted allograft underwent normal physiological load, while the right
      underwent lower load. Animals were killed and specimens taken for examination of
      bone mineral density, bone porosity and maximal three-point-bend breaking load.
      RESULT: The union strength of allograft-host bone junction increased constantly,
      while the internal creeping substitution led to an initial greater weakening of
      the cortical allograft itself and the later recovery of its strength. In
      comparison, the union strength of the normally loaded graft-host surface was
      significantly higher than that of the lower loaded side at eight and sixteen
      weeks after transplantation. At the sixteenth week, there was greater bone
      strength in normally loaded graft than that in less loaded graft. CONCLUSION: The
      internal repair would lead to initial greater weakening of cortical allograft and
      the later gradual recovery of its strength. The effect of physiological load can
      accelerate the improvement of the biomechanical properties of allograft.

PMID- 11825387
TI  - [Haversian remodeling in guided bone regeneration].
AB  - OBJECTIVE: To study the relationship between Haversian remodeling and bone
      regeneration in guided bone regeneration (GBR). METHOD: 10 mm long segmental
      defects were created in the diaphyses of one radius in 24 rabbits. The defect was
      covered with silicone membrane shaped as a tube. Rabbits were killed at the 3rd
      day, 1st, 2nd, 3rd, 4th, 6th, 10th, 12th weeks. Undecalcified section was
      prepared for histologic examination. RESULT: Bone resorption was seen in
      Haversian canal, connection between osteocytes and osteoblasts in Haversian, and
      connection of osteoblasts in Haversian and in callus. The process of Haversian
      remodeling was involved in the process of bone regeneration, just like primary
      bone healing. The process of Haversian remodeling and regeneration was coupled in
      topography, time and size. CONCLUSION: Bone repair is related to Haversian
      remodeling.

PMID- 11825388
TI  - [Influence of stripping periosteum on bone formation in guided tissue
      regeneration].
AB  - OBJECTIVE: To analyze the role of periosteum in guided bone regeneration by means
      of undecalcified sections and X-ray films. METHOD: 10 mm long segmental defects
      were created in the diaphyses of both radii in 24 New Zealand rabbits. The defect
      on the control side was covered with a silicone membrane shaped as a tube. On the
      experimental side, 10 mm periosteum of both sides of the defect was stripped and
      the defect was covered with a silicone tube. The animals were killed at the 3rd
      day and the 1st, 2nd, 3rd, 4th, 6th, 10th, 12th weeks. Samples were treated for
      radiologic and histologic examinations. RESULT: (1) periosteal stripping exerts
      no effect on callus formation in or out of the tube. (2) osteoblasts in the
      cambium layer of the periosteum come from bone surface, endosteum or the
      Haversian envelopes. (3) the tissue in the two layers of the periosteum has
      different origins, the fibrous layer comes from soft tissue and osteoblasts in
      the cambium from bone surface or Haversian envelopes. CONCLUSION: Stripping
      periosteum has no influence on bone formation in guided tissue regeneration.

PMID- 11825389
TI  - [Clinical observation of splenectomy on chronic idiopathic thrombocytopenic
      purpura in 63 patients].
AB  - OBJECTIVES: To investigate the effectiveness of splenectomy in patients with
      idiopathic thrombocytopenic purpura who failed to respond to conservative
      management. METHOD: Sixty-three patients were treated with splenectomy and
      followed up for 2 months to 16 years (average 4.7 years). RESULT: The patients
      had symptoms of bleeding and their platelet count on average was 24 x 10(9)/L.
      The first, 3rd, 5th and 7th day after operation, the average platelet count was
      110 x 10(9)/L, 202 x 10(9)/L, 251 x 10(9)/L and 246 x 10(9)/L. Their platelet
      recovered to normal during a week in 51 cases (80.9%). The total effective rate
      was 86.9% after follow-up for 2 months. The recurrence rate was 17.9% in 39 cases
      after follow-up for longtime. CONCLUSIONS: The curative effect of splenectomy is
      better in children than in adults. In patients with increased platelet have a
      favourable prognosis. Splenectomy is safe and effective in the treatment of
      idiopathic thrombocytopenic purpura.

PMID- 11825390
TI  - [Management of severe Budd-Chiari syndrome by spleen-internal jugular venous
      shunt].
AB  - OBJECTIVE: To study the operative method for severe Budd-Chiari syndrome. METHOD:
      17 patients with severe Budd-Chiari syndrome were treated with splenectomy and
      spleen-internal jugular venous shunt. RESULT: Follow up for 3 to 20 months 11
      patients showed excellent results, 5 good results and 1 died. CONCLUSION: Spleen
      internal jugular shunt is effective for the patients with severe Budd-Chiari
      syndrome.

PMID- 11825391
TI  - [Diagnosis and treatment of duodenal injury].
AB  - OBJECTIVE: To increase the value of early diagnosis and decrease postoperative
      complications of duodenal injury. METHOD: 16 patients with duodenal injury were
      treated and 5 patients were treated successfully with Modified Cogbill's
      techniques. RESULT: We emphasized the importance of early diagnosis and treatment
      of duodenal injury. CONCLUSION: The simplified techniques produce less
      complications and considered to be used clinically application.

PMID- 11825392
TI  - [Coexisting pheochromocytoma and renal artery stenosis].
AB  - OBJECTIVE: To improve the diagnosis of coexisting pheochromocytoma and renal
      artery stenosis. METHOD: Four patients with coexisting pheochromocytoma and renal
      artery stenosis were treated. RESULT: After removal of the pheochromocytoma, the
      blood pressure became normal in two patients combined with resection of kidney
      with renal artery stenosis, and one patient with local adhesion loosened. The
      hypertension, however, persisted in another patient after the resection of
      pheochromocytoma even though the long segment of renal artery stenosis was
      relieved. CONCLUSION: After pheochromocytoma was diagnosed with its known
      position, coexisting renal artery stenosis should be suspected according to one
      of the following conditions: (1) Vascular murmurs are noted at the area of the
      upper abdomen or back; (2) One of the kidneys becomes less sized; (3) Using the
      inhibitor of receptor alpha only has no effect lowering blood pressure and it is
      necessary to add the inhibitor of angiotension; (4) Postoperative hypertension
      does not resolve when no remaining pheochromocytoma is present. the renal artery
      stenosis can be reversed after both removal of pheochromocytoma and loosening of
      adhesion in case of stenosis due to the pressure of the tumor and adhesion caused
      renal artery angling and local stricture. Extensive stenosis or closure, however,
      can not be corrected with severe atrophy of renal parenchyma due to
      pheochromocytoma, and the resection of kidney should be indicated.

PMID- 11825393
TI  - [Thoracoscopic lung reduction surgery for emphysema].
AB  - OBJECTIVE: To study the surgical treatment of emphysema. METHOD: Five patients
      with severe diffused pulmonary emphysema underwent surgical bilateral lung volume
      reduction by video-assisted thoracoscopy. All patients were male and their age
      ranged from 60 to 71 years (mean 64.3 years). Before surgery, 5 patients required
      supplement oxygen with exertion and one oxygen supplement at rest. Preoperative
      and postoperative assessments included standard pulmonary function studies, chest
      CT scan and quantitative nuclear lung perfusion and ventilation scan. Wedge
      resection was performed were in 3 patients, simple plication in 1, and combined
      wedge resection and plication in 1. There were no early or late mortality and no
      requirement for immediate postoperative ventilatory assistance. RESULT: Follow-up
      ranged from 10 to 12 months. After surgery the mean forced expiratory volume in 1
      second (FEV(1)) was significantly increased from 0.46 L to 1.13 L (P < 0.001) and
      the mean forced vital capacity (FVC) was markedly improved from 1.74 L to 2.93 L
      (P < 0.001). Pulmonary compliance was significantly improved and resistance of
      airway decreased (P < 0.001). The mean distance during 6-min walk test increased
      from 10 m to 400 m in 4 patients. CONCLUSION: Thoracoscopic bilateral lung volume
      reduction is an effective and safe technique for patients with severe emphysema.
      It can relieve dyspnea and improve in excise tolerance and quality of life.

PMID- 11825394
TI  - [Treatment of arteriovenous malformation by linear accelerator radiosurgery].
AB  - OBJECTIVE: To summarize the effectiveness of radiosurgery for cerebral
      arteriovenous malformations (AVMs). METHOD: We treated with linear accelerator
      radiosurgery 17 patients harboring AVMs in the brain. 15 AVMs were located
      supratentorially and others infratentorially. All the patients were treated with
      single fraction. The doses at AVM margin were 15 to 30 Gy. RESULT: AVMs
      disappeared in 13 of the 17 patients, reduced in 3 and unchanged in only 1 at 2
      year follow up. Vasogenic edema observed in 2 patients, their neurologic deficits
      were all improved with steroid. CONCLUSION: Linear accelerator radiosurgery is
      effective in dealing with cerebral AVMs. It provides with a new means of
      treatment for AVMs which can't be effectively treated with microsurgery and
      embolization.

PMID- 11825395
TI  - [Multiple subpial transection in surgical treatment of intractable epilepsy].
AB  - OBJECTIVE: To increase the effect of epilepsy surgery, we use multiple subpial
      transection (MST) clinically on the basis of experimental study. METHOD: We
      analyzed the seizure type and course of 116 intractable epilepsy patients treated
      with MST and surgical technique were modified. RESULT: 100 patients were followed
      up for 1 to 5 years. Complete control of seizure was obtained in 62 patients
      (62%), significant reduction (over 75%) in 20 (20%), reduction (over 50%) in 12
      (12%), and no change in 6 (6%). The total effective rate was 94%, and the
      significant effective rate was 82%. No functional defect was found in any
      patients. CONCLUSION: MST is a effective in surgical treatment of intractable
      epilepsy and can replace conventional methods. Combined bilateral frontal lobe
      MST and anterior callosotomy is a good way to treat intractable generalized
      epilepsy.

PMID- 11825396
TI  - [Prognostic value of tumor vascularity in gastric carcinoma].
AB  - OBJECTIVE: To determine whether tumor angiogenesis correlates with progression of
      gastric carcinoma. METHOD: Microvessel counts (MVC) of 131 specimens resected
      from patients with gastric carcinoma were investigated by immunohistological
      staining with a monoclonal antibody against F-VIII RAg, counting the mean number
      of microvessels in the five areas of highest vascular density under 200 times
      magnification microscopy. Correlation among MVC, various clinicopathologic
      factors, and prognosis was studied. RESULT: MVC increased with TNM stage, the MVC
      of patients with advanced stage disease was significantly higher than that of
      early stage patients (P < 0.01). MVC was significantly higher in tumors with deep
      penetration (P < 0.05), lymph node metastasis (P < 0.001) and distant metastasis
      (P < 0.05) than in those without invasion and such metastasis. The recurrence
      rate after curative resection in hypervascular group (MVC > or 16) was 58.4%,
      which was significantly higher (P < 0.05) than that in the hypovascular group
      (MVC < 16). Moreover, the prognosis of patients with a high MVC was significantly
      poorer than that of those with a low MVC. The probability of 5 year survival rate
      was estimated by P = e(1.6231-0.1036 x MVC)/1 + e(1.6231-0.1036 x MVC).
      Multivariate analysis indicated that MVC is an independent prognostic factor in
      gastric cancer. CONCLUSION: Angiogenesis within gastric cancer is an indicator of
      tumor behavior and may identify patients at higher risk for recurrence and poorer
      prognosis.

PMID- 11825397
TI  - [Expression of oncogene ras product p21 protein in the tissues of penis cancer
      and its surrounding tissues].
AB  - OBJECTIVE: To explore the clinical significance of expression of oncogene ras
      product p21 protein in the tissues of penis cancer and its surrounding tissues.
      METHOD: Oncogene ras product p21 protein in 32 cases of penis cancer, 32 cases of
      para-carcinoma tissues and in 16 cases of normal penis tissues were detected by
      immunohistochemical ABC method. RESULT: p21 protein expressed in 28 cases of
      penis cancer and 8 cases of para-carcinoma tissues, but it did not express in 16
      cases of normal penis. Expression of p21 protein was related to pathological
      grading and clinical stage i. e, expression of p21 protein enhanced with the
      increasing of grading and stage. The positive cases of p21 protein expression in
      para-carcinoma tissue had worse impact on the prognosis of early recurrence and
      metastasis. CONCLUSION: p21 protein could be used as predictor of malignant
      potential and prognosis of penis cancer.

PMID- 11825398
TI  - [CD44v and nm23-H1 gene product expression and its clinical significance in human
      recurrent bladder cancer].
AB  - OBJECTIVE: To investigate the expression of the CD44v and nm23-H1 gene products
      and its clinical significance in human recurrent bladder cancer. METHOD: The
      CD44v and nm23-H1 gene products in 45 cases of bladder cancer were analysed
      quantitatively by flow cytometry and cytoimmunofluorescence staining. RESULT: The
      CD44v gene product overexpression and nm23-H1 gene product low expression were
      correlated with invasive extent and recurrence of bladder cancer (P < 0.05). The
      correlation coefficients between CD44v gene product and nm23-H1 gene product were
      gamma = -0.2876 in bladder cancer. The correlation coefficients between CD44v
      gene product and nm23-H1 gene product were gamma = -0.4238 in recurrent bladder
      cancer. CONCLUSION: The expression of CD44v and nm23-H1 gene product cooperated
      in growth and progress of bladder cancer. Both CD44v and nm23-H1 gene products
      were an objective indication of invasive extent and recurrence of bladder cancer.

PMID- 11825399
TI  - [Subpopulations of TIL in renal cell carcinoma and their clinical significance].
AB  - OBJECTIVE: To study the relationship between tumor-infiltrating lymphocytes (TIL)
      and the prognosis of patients with renal cell carcinoma. METHOD:
      Immunohistological chemistry method was employed to semiquantitatively assess the
      expression of TIL and its subpopulations. The prognostic values of various TIL
      subpopulations were also evaluated. RESULT: T-lymphocyte was the main component
      of TIL, B-lymphocyte, monocyte, and nature killer (NK) cells were also presented
      but in relatively small numbers. T-lymphocyte was strongly correlated to the
      survival probability, but this correlation was not observed between the host
      survival and TIL or other subpopulations. CONCLUSION: T-lymphocyte can represent
      the host immunological status and can be used to judge the prognosis of patients
      with renal cell carcinoma.

PMID- 11825400
TI  - [Nitric oxide in pathogenesis of cirrhotic portal hypertension in rats and its
      hemodynamic effects].
AB  - OBJECTIVE: To measure serum nitrite and nitrate levels as an index for in vivo
      nitric oxide generation in rats at different stages during the development of
      cirrhosis with portal hypertension. METHOD: Plasma endotoxin and hemodynamic
      parameters were measured. The effects of NO-monomethyl-L-arginine (L-NMMA), an
      inhibitor of NO biosynthesis were investigated in rats with cirrhosis. RESULT:
      Significant increase was noted in serum nitrite/nitrate and plasma endotoxin
      compared with controls at each stage of cirrhosis. At each stage, the mean
      arterial pressure (MAP) and splanchnic vascular resistance (SVR) were
      significantly lower than those of controls, whereas portal venous pressure (PVP)
      and portal vascular resistance (PVR) significantly increased and portal venous
      flow (PVF) was not markedly different from that of the controls. In addition, the
      serum nitrite/nitrate levels significantly were correlated with endotoxemia and
      PVP. Intravenous bolus administration of L-NMMA (25 mg/kg) significantly
      increased MAP, PVR and SVR in cirrhotic rats. L-NMMA also significantly decreased
      PVF but did not alter PVP and IVCP. CONCLUSION: The excessive synthesis and
      release of NO plays a key role in the induction of portal hypertension.

PMID- 11825401
TI  - [Long-term results of combined splenorenal shunt and porta-azygos
      devascularization in patients with portal hypertension].
AB  - OBJECTIVE: To investigate the long-term effects of combined splenorenal shunt and
      porta-azygos devascularization in patients with portal hypertension. METHOD: We
      analysed retrospectively the follow-up results of 140 portal hypertensive
      patients undergoing the combined therapy in our hospital from April 1978 to April
      1997. Changes of portal hemodynamics were studied by Doppler Flowmeter and DSA
      pre- and-postoperatively and direct FPP measurement intraoperatively. RESULT: The
      operative mortality was 3.6%. No rebleeding was noted in a short period and
      rebleeding rate was 8.3% in a long term follow-up. The rate of postoperative
      hepatic encephalopathy was 5.0%. The long-term survival rate of 5-, 10- and 15
      years was 83.6%, 64.5% and 54.5%, respectively. After operation FPP and PVP
      decreased significantly (P < 0.01) and FPP maintained at the level of 3.2 +/- 0.4
      kPa. CONCLUSION: The combined procedure is a rational and practical procedure for
      the treatment of patients with portal hypertension.

PMID- 11825402
TI  - [Portacaval shunt with H-grafts of small diameter in treating cirrhotic patients
      with portal hypertension].
AB  - OBJECTIVE: To evaluate the effectiveness of portacaval shunt with H-grafts of
      small diameter in the treatment of cirrhotic patients with portal hypertension.
      METHOD: 48 patients cirrhotic with portal hypertension were randomized into three
      groups: portacaval shunt with H-grafts of 8 mm diameter with external ring
      reinforced (20 patients), proximal splenorenal shunt (17), and side-to-side
      portacaval shunt (11). The preoperative liver function in Child's grade and the
      history of variceal bleeding were the same in the three groups. RESULT: The
      postoperative decrease in portal pressure was comparable in the three groups
      (0.83 +/- 0.31 kPa, 0.81 +/- 0.50 kPa, and 1.02 +/- 0.45 kPa, P > 0.05). There
      was no significant difference in postoperative rebleeding rate during the follow
      up for 15-28 months, and in hospital mortality between the three groups. However,
      postoperative encephalopathy developed much less in patients undergoing
      portacaval shunt with H-grafts than those receiving side-to-side portacaval shunt
      (5.0% vs. 36.4%, P < 0.05). Postoperative transfemoral portography performed
      within one month showed shunt patency in 95% of the 20 patients undergoing H
      graft shunting. B-mode ultrasonography follow-up of up to 15 months also showed
      shunt patency in all 19 survivals receiving H-graft shunt. CONCLUSION: This
      procedure shows less trauma, lower postoperative encephalopathy rate, while as
      effective in preventing recurrent variceal bleeding as the traditional
      portosystemic shunt.

PMID- 11825403
TI  - [Treating portal hypertension by subtotal splenectomy with retroperitoneal
      splenic transposition and devascularization: clinical study].
AB  - OBJECTIVE: To devise a new surgical procedure for improving the operative effect
      of portal hypertension caused by hepatic cirrhosis. METHOD: In treatment group,
      subtotal splenectomy with retroperitoneal transposition was performed in 36
      patients of cirrhotic hypertensives. In control group, 36 patients were treated
      by devascularization. The follow-up period ranged from 3 months to 5.5 years
      (average 26 months). RESULT: In the treatment group, the rates of disappearance,
      improvement and absence of changes of esophageal varices were 11.5%, 61.5% and
      26.9%, respectively, and in the control group those of improvement were 50.0%,
      absence of change 45.8% and aggravation 4.2%. There was a significant difference
      between them (P < 0.05). In the treatment group, hypersplenism disappeared in
      all. There was also significant difference between the two groups in
      immunological indexes (P < 0.05). DSA showed abundant collateral circulation in
      the residual spleen and retroperitoneal wall, which enabled the portal blood flow
      diverting to retroperitoneal tissues. CONCLUSION: This method possesses the
      advantages of devascularization and decompression shunt. It is of value in
      retaining part of spleen in surgical treatment of portal hypertension.

PMID- 11825405
TI  - [Treatment of portal hypertension by using pericardial vascular disconnection and
      mesocaval side-to-side shunting].
AB  - OBJECTIVE: To prevent post-operative bleeding, to maintain the blood supply to
      the liver from the portal vein and to reduce the incidence of hepatic
      encephalopathy. METHOD: The blood vessel was cut around the cardial opening and
      the venae cavae was anastomosed in 37 patients with portal hypertension. RESULT:
      The success rate of surgery was 100%. The free portal pressure (FPP) was 3.16 +/-
      0.581 kPa, which was lower than the FPP (3.91 +/- 0.642 kPa) before operation (P
      < 0.01). Follow-up for 5 to 22 months showed that liver function recovered from
      III to I in 5 patients, and from III to II in 7. Ascites disappeared in all and
      varix improved in 82.9% patients. CONCLUSION: Cutting flow combined with fraction
      flow can effectively maintain the blood supply to the liver in treating portal
      hypertension.

PMID- 11825404
TI  - [Distal spleno-caval shunt in 66 patients with portal hypertension].
AB  - OBJECTIVE: To evaluate the long-term results and operative experience of distal
      splenocaval shunt. METHOD: 66 patients with portal hypertension were treated by
      distal spleno-caval shunt. Of these patients 57 were males and 9 females with a
      mean age of 39 years. All the patients were followed up. RESULT: The operative
      mortality rate was 7.58%. Only 5 patients experienced recurrent bleeding (7.58%).
      None of the patients had clinical hepatic encephalopathy. Five-year survival rate
      was 70.45%. CONCLUSION: Distal splenocaval shunt is suitable for portal
      hypertension patients with hepatopetal portal flow.

PMID- 11825406
TI  - [Influence of transjugular intrahepatic portosystemic stent shunts on portal and
      systemic hemodynamics of patients with portal hypertension].
AB  - OBJECTIVE: To determine the influence of transjugular intrahepatic portosystemic
      stent shunts (TIPSS) on portal and systemic hemodynamics of patients with portal
      hypertension. METHODS: Fifteen patients who had undergone TIPSS with 10 mm stents
      were studied. The parameters of portal, systemic and pulmonary hemodynamics were
      measured with Doppler sonography, direct portal pressure measurement, blood-gas
      analysis and Swan-Ganz catheter before and 30 min and 2 weeks after TIPSS.
      RESULT: Portal pressure decreased by 34% and 55.4%, and PO(2), SatO(2) increased
      by 67.7%, 21.3% and 68%, 20.4% respectively 30 min and 2 weeks after TIPSS.
      Portal blood velocity increased by 1.4 times 2 weeks after TIPSS. CO, CI, SI
      increased (P < 0.01) and SVR, PVR decreased (P < 0.01) after TIPSS. Also, RAP,
      PAP increased (P < 0.05). Renal blood flow increased (P < 0.01) and renal
      function significantly improved. CONCLUSION: TIPSS can not only decrease portal
      pressure and improve renal function, but also worsen portal and systemic
      hemodynamics. Cardiac and liver function should be monitored before and after
      TIPSS.

PMID- 11825407
TI  - [Comparative study of portal-systemic shunt rate measured by formula and
      radioactive method].
AB  - OBJECTIVE: To establish a new simple and useful formula for the observation of
      portosystemic shunt. METHOD: In the same animals and the same patients,
      portosystemic shunt rate was measured individually by the two different methods,
      i.e. formula and radio active method. Using the results of the radio active
      method as a gold standard, the reliability of the formula method was assessed
      tested. RESULT: In 11 normal dogs, the portal-systemic shunt rate measured by the
      formula and radio active methods was 7.03% and 7.55% respectively (P > 0.05). In
      9 portosystemic shunting model dogs, the portosystemic shunt rate calculated from
      the two methods was 48.64% and 51.11% respectively (P > 0.05). In 22 patients
      with portal hypertension, the preoperative results from the formula and
      radioactive methods were 52.38% and 55.86% respectively (P > 0.05). In these
      patients, the postoperative portal-systemic shunt rate was 26.22% and 31.00%
      respectively (P > 0.05). CONCLUSION: These results fully testified the
      reliability of the formula method we had established.

PMID- 11825409
TI  - [Intrahepatic portal vein compliance in cirrhosis].
AB  - OBJECTIVE: To elaborate the effects of increase in portal flow on intrahepatic
      vein compliance with isolated perfused cirrhotic model (IPCM). METHOD: Cirrhosis
      was induced by CCl(4) in 80 Wistar rats, which were divided into two groups A and
      B, by portal with/without hepato-artery. Portal flow was increased and
      hemodynamic parameters were recorded and analysed. RESULT: In group A, compared
      with 1.65 +/- 0.28 kPa at basal control, portal pressure was elevated from 2.55
      +/- 0.40 kPa to 3.96 +/- 0.67 kPa. Q(35)-Q(55) flow rates were raised from 35 to
      55 ml/min, respectively. A correlation existed between portal flows and pressures
      (r = 0.985, P < 0.01). The low flow rate of 15 ml/min at Q(15) caused a
      irreversible model injury. A largest flow rate in IPCM was, less than in IPRL. In
      group B, no low flow-injury was found. CONCLUSION: Portal vein compliance of
      liver is decreased markedly in cirrhotic portal hypertension, but hepatic flow is
      increased. There are likely some compensative relations between portal and hepato
      arterial system.

PMID- 11825408
TI  - [Histamine-1 and -2 receptors in hepatic tissues of cirrhotic patients with
      portal hypertension].
AB  - OBJECTIVE: To study histamine-1 and histamine-2 receptors in hepatic tissues of
      cirrhotic patients with portal hypertension. METHOD: Light autoradiography was
      used. RESULT: The density of histamine-2 (H-2) receptors (cirrhotic
      patients/controls) in hepatocytes was 168.4 +/- 22.6/511.9 +/- 37.6 (P < 0.01),
      in hepatic vein 238.8 +/- 40.7/313.0 +/- 52.4 (P < 0.01), in hepatic artery 55.6
      +/- 7.1/175.4 +/- 26.1 (P < 0.01), and in portal vein 52.0 +/- 5.4/166.4 +/- 17.7
      (P < 0.01). The density of histamine-1 receptors in hepatocytes, hepatic vein,
      hepatic artery and portal vein was not statistically changed between cirrhotic
      patients and controls (P > 0.05). CONCLUSION: The density of H-2 receptors in
      hepatic tissues of cirrhotic patients decreased significantly.

PMID- 11825410
TI  - [Clinical diagnostic standard of mediopatellar plica syndrome].
AB  - OBJECTIVE: To increase the level of clinical diagnosis of mediopatellar plica
      syndrome. METHOD: We reviewed the preoperative clinical symptoms of 67 knee
      joints that were proved to have pathologic mediopatellar plica by arthroscopy.
      RESULT: Mediopatellar plica syndrome had the following clinical symptoms: painful
      knee and mediopatellar tenderness in all patients; tender bands in 56.7%
      patients; positive test of flexion or extension with internal femoral condyle
      pressed in 62.7% patients; positive Mcmarry's sign in 31.3% patients. CONCLUSION:
      The clinical diagnostic standard of mediopatellar plica syndrome is that the
      first above-mentioned clinical symptom plus one of other three symptoms could
      suggest the diagnosis, while the first clinical symptom plus two or three of
      other three symptoms could define the diagnosis.

PMID- 11825411
TI  - [Intracardiac operations performed in beating heart through mini-thoracotomy in
      34 patients].
AB  - OBJECTIVE: To introduce the technique of intracardiac operations performed in
      beating heart through mini-thoracotomy. METHOD: >From March 1995 to June 1997,
      intracardiac operations were performed in beating heart through right subaxillary
      anterolateral mini-thoracotomy with normothermic extracorporeal circulation in 34
      patients. 16 patients had atrial septal defect, 14 ventricular septal defect, 2
      mitral insufficiency, 1 right coronary artery-right ventricular fistula, and 1
      Ebstein's anomaly. RESULT: The mean cardiopulmonary bypass time was 22.54
      minutes. There were no embolism, arrhythmia and cerebral complications.
      Postoperative hospital stay was 8.0 +/- 2.2 days. All the patients had no heart
      murmur and residual shunt, and enjoyed a full range of physical activities in a
      follow-up of 2 to 26 months. CONCLUSION: Intracardiac operations performed in
      beating heart through right subaxillary anterolateral mini-thoracotomy appears to
      be less invasive, simple, safe and cosmetic.

PMID- 11825412
TI  - [Long-term follow-up study of postoperative revascularization in childhood
      moyamoya disease: results of 226 cases].
AB  - OBJECTIVE: To study the long-term results of 226 patients with moyamoya disease
      ased below 15 years and to report the modified method of extra-intracranial
      arterial anastomosis and encephalo-myo-arterio-syn-anastomosis, etc. METHOD: The
      mean follow-up period was 15.5 years (range 8 - 19 years). The results were
      obtained from the pre- and postoperative cerebral angiographic examination, MRI,
      CT, cerebrovascular Doppler ultrasonography, Glasgow Outcome Scale (GOS),
      intelligence quotient (IQ) as classified by Taft and neurological symptoms.
      RESULT: Of the 226 patients with childhood moyamoya disease, 64 (28%) recovered
      in completely, 69 (31%) in improved markedly, and 46 (20%) improved slightly. 43
      patients (19%) had no changes and 4 (2%) died. The effective rate of the
      operation was 79%. CONCLUSION: The modified direct anastomosis and encephalo-myo
      arterio-synagiosis played a role in this improvement by increasing CBF after the
      operation. A significant correlation is found between the postoperative effect
      and the stages of preoperative angiograms.

PMID- 11825413
TI  - [Clinical application of 2 mm micro-thoracoscopic surgery].
AB  - OBJECTIVE: To determine the clinical safety and efficacy of micro-thoracoscopic
      surgery. METHOD: From July 1996 to July 1997, video-assisted thoracoscopic
      surgery was performed in 47 patients by using 2 mm microthoracoscope. There were
      36 males and 11 females. Their age ranged from 40 to 75 years with a mean age of
      56.7 years. Surgical procedures included bullectomy (16 patients), wedge
      resection (3), lung cancer staging (4), lobectomy (2), exploration (15), and
      resection of mediastinal tumor (2), esophagectomy (1) and repair of pneumothorax
      (4). Local anesthesia was employed in 18 patients and general anesthesia with
      double lumen endotracheal tube in 29. RESULT: There were no operative mortality
      and postoperative complications. CONCLUSION: 2 mm micro-thoracoscopic surgery
      could be used in the management of a variety of thoracic conditions. It may be of
      significant value for diagnostic and therapeutic purposes, but the further study
      for this new technique is required to determine its safety and efficacy.

PMID- 11825414
TI  - [The effects of Chinese medicine herb mixture on cell-mediated immune functions
      and four kinds of acute-phase reaction proteins in burn patients].
AB  - OBJECTIVE: To search for immunomodulators to improve postburn immune function
      disorder. METHOD: We studied the Chinese medicinal herbs. On the basis of
      previous data, we prepared a kind of Chinese medicinal herbal mixture and studied
      its effects in vivo and in vitro. RESULT: The mixture could restore the cell
      mediated immune response such as the production of interleukin 2 and the T cell
      proliferative ability, and could also adjust the levels of serum acute-phase
      reaction proteins, i.e, haptoglobin, prealbumin, transferrin and alpha 1-acid
      glycoprotein. CONCLUSION: The Chinese herbal mixture showed immune regulatory
      effects on body defence imbalance and also on acute phase reaction proteins in
      burn patients.

PMID- 11825415
TI  - [Clinical analysis of laser prostatectomy].
AB  - OBJECTIVE: To study the effect of laser prostatectomy for benign hypertrophy of
      prostate by transurethral noncontact laser ablation. METHOD: 204 patients with
      benign prostatic hyperplasia were treated by transurethral noncontact laser
      ablation. RESULT: 163 patients resumed urination in a week, and 37 in two weeks.
      Four patients were treated by open procedure. Patients were followed up for 14
      months. Symptomatic scores (I-PSS) exceeded the middle rank in 90% patients and
      the maximum urinary flow rate was 89%. CONCLUSION: It is an effective method for
      adjusting the strength, direction, range and frequency of laser to prevent
      bleeding, perforation and long-term urethral stricture.

PMID- 11825416
TI  - [Apoptosis of renal cell carcinoma and apoptotic related genes bcl-2 and bax].
AB  - OBJECTIVE: To explore the mechanism of renal cell carcinoma (RCC). METHOD: We
      detected the apoptotic status and the expression of apoptotic related gene bcl-2
      and bax protein in 48 cases of RCC with TdT-mediated dUTP-biotin nick end
      labeling (TUNEL) and immunohistochemistry methods. RESULT: 22 cases showed low
      expression of bcl-2 protein with an average apoptotic index (AI) of 1.35 and 26
      cases had high expression of bcl-2 with an AI of 1.04 (P < 0.05). 34 cases showed
      low expression of bax protein with average AI of 1.03 and 14 cases had high
      expression of bax protein with an average AI of 1.63 (P < 0.01). The stronger bcl
      2 expression, the weaker bax expression and the less number of apoptotic cells.
      CONCLUSION: both bcl-2 and bax take part in the occurrence and progression of
      RCC.

PMID- 11825417
TI  - [The enzymes activity of intestine grafts after combined small bowel/liver
      transplantation in rats].
AB  - OBJECTIVE: To study the alteration of the enzymes activity of intestine grafts
      after combined small bowel/liver transplantation in rats and the relations
      between their changes, functions and immune rejection. METHOD: A kind of model of
      combined small bowel/liver transplantation (SLT) was established in SD closed
      colony rats. The enzymes activity of grafts were examined at regular
      postoperative intervals with histochemical methods. RESULT: The enzymes activity
      of grafts disappeared eventually in isolated small bowel transplantation rats.
      Contrary, those in SLT rats were remained and recovered after operation.
      CONCLUSION: The rejection in grafted intestine can be prevented or delayed in SLT
      rats. The examination of activity of enzymes and nerves in grafts may be used to
      monitor rejection and study function of grafts.

PMID- 11825418
TI  - [The effect of chitosan in prevention of fibrous scar tissue formation after
      laminectomy].
AB  - OBJECTIVE: To study the effect of chitosan in the prevention of fibrous scar
      formation in the epidural space after laminectomy. METHOD: Fourty-eight SD rats
      were used as the animal model. Laminectomy was performed in lumber 1, and the
      exposed dura was covered with hyaluronate (group A), free fat (group B), chitosan
      (group C), and saline solution (group D) respectively. At 4, 8 and 12 weeks
      postoperation, scar formation was observed. RESULT: The results revealed that
      scar formed in the group D at the fourth week reached a peak at the eighth week
      and began to soften and constrict at the twelfth week. Sodium hyaluronate and
      chitosan had a significant efficacy in the prevention of scar formation, but the
      effect of chitosan was superior to that of sodium hyaluronate. CONCLUSION: The
      findings of this study indicate that chitosan has a preventive effect on scar
      tissue formation.

PMID- 11825419
TI  - [Endovascular treatment of intracranial aneurysms with GDC: report of 8 cases].
AB  - OBJECTIVE: To assess the usefulness and practical experience in intracranial
      aneurysm embolization with guglielmi detachable coil (GDC) applied firstly in
      China. METHOD: Under general anesthesia and systematic anticoagulation, eight
      cases of intracranial aneurysms were embolized with GDC which was introduced by
      tracker micro-catheter, combined remodeling technique (RT) if necessary. RESULT:
      100% occlusion was achieved in 5 cases, 95% in 2 and 90% in 1, without any
      complication. Among these cases, 4 failed in the previous attempts of
      endovascular treatment with mechanical detachable system (MDS), because MDS could
      not be safely and totally placed inside the aneurysms and Mag 3F/2F micro
      catheter could not be navigated into the aneurysms. CONCLUSION: Embolization of
      intracranial aneurysms with GDC is safe, effective and reliable, and it may offer
      the cure opportunity to those enearysms which are very dangerous to embolize or
      can not be embolized with MDS.

PMID- 11825420
TI  - [Animal experiment and clinical application of self-made mechanically detachable
      coils].
AB  - OBJECTIVE: To evaluate the practical and thrombogenetic characteristics of self
      made mechanically detachable coils by the animal experiment and primary clinical
      application. METHOD: The bifurcation type of aneurysm model was established on
      rabbit and embolized with self-made mechanically detachable coils 2 weeks after
      surgery. 24 coils were used in 5 experimental aneurysms. Control angiography was
      performed and the rabbits were sacrificed 2 - 3 weeks after the embolization. The
      embolized aneurysm samples were examined by pathologist. Ten patients were
      treated with self-made mechanically detachable coils in primary clinical
      application. They were divided into aneurysms (7 patients), traumatic carotid
      carvenous fistulas (2), dural arterio-venous fistula in carvenous sinus region
      (1). 146 coils were used totally and all were delivered with mechanical
      detachable system (MDS Balt co. France). RESULT: Pathologically, the cavities of
      rabbit aneurysm models were occluded by tungsten coils (2 complete, 3 almost
      complete). The coils were trapped in granulation tissue which was covered by a
      thin layer of endothelium on the surface facing the blood flow. In the coils
      dense packing ones, the aneurysms were completely excluded from the parent
      circulation by neointimal layers. In the practice procedures, the coils fit MDS
      (Balt co. France) very well and can be delivered, withdrew and detached smoothly.
      CONCLUSION: The self-made mechanically detachable coils have practical
      reliability and evident thrombogenetic effects.

PMID- 11825421
TI  - [Interventional endovascular therapeutic modalities of giant intracranial
      aneurysm].
AB  - OBJECTIVE: To treat 28 cases of intracranial giant aneurysms in the last 7 years
      and study the therapeutic methods and their effectiveness on this disease.
      METHOD: The cases of giant aneurysms were divided into several groups. The
      advantages and disadvantages of the methods were compared. The main modality of
      endovascular therapy was to use balloon to occlude the parent artery. RESULT: In
      the 16 cases treated by the proximal balloon occlusion, 13 were cured
      angiographically with complete obliteration of the aneurysmal sac and in 4 of
      them the aneurysms disappeared both on CT and MRI. No deterioration after
      operation was encountered with the exception of 2 deaths. CONCLUSION:
      Endovascular therapy can cure the intracranial aneurysms which were difficulty
      treated by direct open operation.

PMID- 11825422
TI  - [The preliminary analysis of domestic hydrogel microspheres for endovascular
      embolization].
AB  - OBJECTIVE: To evaluate the embolic effects and biocompatibility of domestic
      hydrogel microspheres (HMs). METHOD: 22 domestic rabbits were used. 0.03 g/2ml,
      0.06 g/2ml domestic Hms of 70 - 150 microm and 2 ml normal saline were injected
      respectively through catheterization in the right common carotid arteries of
      rabbits. The changes in neurologic functions, general state and average weight of
      rabbits were observed, and the histomorphological changes of embolized arteries
      and surrounding tissues were evaluated by analysis of macroscopy and light
      microscope. RESULT: Rabbits' neurologic symptoms (hemiparalysis, convulsion and
      hypotonia) and death were observed after embolization. Thrombogenesis was present
      and the entire cross sections of blood vessels could easily be embolized. Neither
      acute and chronic inflammatory cells nor remarkable general toxic and side
      effects were shown in rabbits. CONCLUSION: Domestic HMs can effectively block the
      vessels, and they have the characteristics of good biocompatibility. The kind of
      domestic HMs is a promising particulate embolic agent in clinical sets.

PMID- 11825423
TI  - [Endovascular treatment of carotid-cavernous sinus fistulae].
AB  - OBJECTIVE: To treat carotid-cavernous sinus fistulae mmunications between 43
      patients with endovascular procedure. METHOD: Of the 43 patients 37 were male and
      6 female. Traumatic and spontaneous CCF were noted in 39 and 4 patients
      respectively. 36 patients with CCF were given ICA alone, both internal and
      external carotid arteries in 7. Fistulae occlusion in 31 patients and ICA
      obliteration in 12 patients were achieved with transarterial detachable balloon
      technique. External carotid feeding arteries were embolized with silk suture in 7
      patients. RESULT: Angiographic and clinical cure wer obtained in 39 patients and
      improved in 4. One patient was complicated by hemiplegia postoperatively.
      CONCLUSION: Endovascular balloon embolization is the first method of choice in
      dealing with carotid-cavernous fistulae.

PMID- 11825424
TI  - [Correction of cardiac defects through a right minithoracotomy in children].
AB  - OBJECTIVE: To review the experience of correction of congenital cardiac defects
      through a right minithoracotomy. METHOD: 319 patients underwent correction of
      congenital heart malformations through right lateral thoracotomy under
      cardiopulmonary bypass. The average age was 3.44 +/- 1.59 years (range, 5 months
      8 years). The average body weight was 13.66 - 3.98 kg (range, 6 - 26 kg). Cardiac
      defects repaired included atrial septal defect in 87 patients (1 patient
      associated with left superior vena cava (LSVC), 6 pulmonary stenosis, 5 partial
      anomalous pulmonary venous connection), ventricular septal defect in 200 (7
      patients with coexisting patent ductus arteriosus, 7 mitral insufficiency, 3
      LSVC, 11 right ventricular outflow tract obstruction), Fallot's Tetralogy in 19
      (3 patients associated with LSVC, 1 single coronary malformation), partial
      endocardial cushion defect in 2 and other defects in 11. The mean cardiopulmonary
      bypass time was 56.07 +/- 24.90 min (range, 20 - 176 min) and the mean aortic
      crossclamping time was 32.97 +/- 20.38 min (range, 6 - 140 min). The average
      mechanical ventilation time after operation was 18.75 +/- 24.57 hr (range, 2 -
      140.72 hr), and the mean postoperative hospital stay was 7.08 +/- 0.69 days
      (range, 7 - 17 days). RESULT: No operative mortality and severe postoperative
      complications were noted. CONCLUSION: The right lateral thoracotomy is a safe and
      effective alternative to a median sternotomy for correction of cardiac defects.
      Advantages of this approach include less injury, maintaining the continuity and
      the integrity of the bony thorax, and preventing postoperative pigeon breast. The
      cosmetic result is superior to that of median sternotomy or bilateral submammary
      incision.

PMID- 11825425
TI  - [Diagnosis and treatment of periampullary diverticulum].
AB  - OBJECTIVE: To provide a better surgical method for periampullary diverticulum,
      its teraninology and typing, and some experience in its diagnosis. METHOD: In 11
      cases of recurrent cholangitis or (and) pancreatitis resulting from periampullary
      diverticula juxta-ampullary diverticula was observed in 9, intra-ampullary
      diverticulum in 1, and ampullocele in 1. All patients underwent elective
      operation including combined diverticulo-sphincteroplasty (7 cases),
      diverticulectomy with sphincteroplasty (2), diverticulectomy (1), and
      papilloplasty (1). RESULT: The perioperative and long-term results were
      excellent. There were no recurrence and morbidity. CONCLUSION: The combined
      diverticulo-sphincteroplasty is simpl, safe, effective for the treatment of juxta
      ampullary diverticula.

PMID- 11825426
TI  - [Expression and significance of Fas/APO-1 and bcl-2 protein in renal cell
      carcinoma].
AB  - OBJECTIVE: To investigate the role of Fas/APO-1 and bcl-2 in occurrence and
      progression of renal cell carcinoma. METHOD: Immunohistochemistry method was used
      to detect the expression of Fas/APO-1 and bcl-2 protein in 35 cases of renal cell
      carcinoma tissues and 26 cases of normal renal tissues. RESULT: The expression
      rate of Fas/APO-1 protein in renal cell carcinoma tissues was 57.14%,
      significantly lower than that in normal renal tissues (84.62%) (P < 0.05), and
      the intensity of expression was also lower. The expression rate of bcl-2 protein
      reached 80.00%, much higher than that in normal renal tissues (53.85%) (P <
      0.05). CONCLUSION: Both Fas/APO-1 and bcl-2 take part in the occurrence and
      progression of renal cell carcinoma.

PMID- 11825427
TI  - [Three cases of Dieulafoy's disease].
AB  - OBJECTIVE: To increase the knowledge of Dieulafoy's disease and decrease the
      misdiagnosis rate. METHOD: Three cases of Dieulafoy's disease were analyzed
      clinically and their therapeutic methods were discussed. RESULT: Subtotal
      gastrectomy including the lesion is better than other methods. CONCLUSION: It is
      necessary to understand the clinical pattern and pathological characteristics in
      order to increase the diagnosis rate and decrease misdiagnosis rate. Subtotal
      gastrectomy or wide wedge resection of the lesion is recommended.

PMID- 11825428
TI  - [Local amyloidosis of stomach].
AB  - OBJECTIVE: To improve the diagnostic rate of local amyloidosis of stomach.
      METHOD: One case of local amyloidosis of stomach was reported and the literatures
      were reviewed on the etiopathology, clinical features, diagnosis, treatment and
      prognosis. RESULT: The patient was negative for family history and other chronic
      disease. Total gastrectomy was taken and was eventually found to have localized
      amyloidosis of stomach and regional lymph nodes. The amyloidosis was found to be
      of AA amyloidosis. Multiple biopsy specimens taken from esophagus, duodenum,
      rectum and bone marrow showed no amyloid deposition. CONCLUSION: Amyloidosis
      should be considered in the differential diagnosis of gastric tumors, and also
      should be removed by operation if complications are to be prevented.

PMID- 11825429
TI  - [The effects of graded spinal cord injuries on transcranial electric stimulation
      motor evoked potentials in the rat].
AB  - OBJECTIVE: To study the effects of graded spinal cord injury (SCI) on the motor
      evoked potentials (MEP) characteristics and the prognostic value of MEP for the
      motor function. METHOD: Modified Allen's method was used by weight drop force of
      30 gcf, 50 gcf, 80 gcf and 100 gcf on the T(8 - 9) spinal cord of 40 SD rats in
      order to make SCI models. MEP was recorded continuously at L(1 - 2) epidurally
      and bilateral gastrocnemius muscles before and after the spinal cord lesion was
      produced (followed up for 1 month). The inclined plane and Tarlov technique were
      used to assess clinical neurological function. RESULT: The amplitude of rat's MEP
      changed significantly with graded SCI, the more sever the lesion, the lower the
      potentials. mMEP was more sensitive than scMEP, though the abolishment of mMEP
      soon after SCI didn't indicate that the animals could not regain ambulation.
      Changes in amplitude of scMEP recorded early after SCI were collaborate
      significantly with inclined plane (gamma = 0.9665, P < 0.01) and Tarlov scale
      (gamma = 0.8893, P < 0.01) assessed 1 month later, and can be used as a chronic
      measure parameter of motor function prognosis. scMEP still existed 1 month after
      SCI in 3 of 11 rats (27.3%) without any voluntary movement in bilateral
      hindlimbs, suggesting that some parts of conductive function still existed in the
      spinal cord. So it should be called "discomplete SCI". CONCLUSIONS: scMEP can be
      used as a reliable parameter for motor function prognosis, because it reflects
      objectively and sensitively the severity of central motor neurol fiber injury.

PMID- 11825430
TI  - [Preserving remnant liver function after major hepatic vein occlusion].
AB  - OBJECTIVE: To observe the pathological changes of the remained hepatic lobe after
      major hepatic vein (MHV) occlusion. METHOD: Seventy-eight rats were randomly
      divided into the control group, the ligation group of segmental hepatic vein, the
      stricture group of left MHV, and the ligation group of left MHV. The pathology,
      hepatic microcirculation and hemodynamic changes of the involved hepatic lobe of
      MHV occlusion were dynamically determined. RESULT: Necrosis occurred in the
      hepatocytes at the first postoperative day in the ligation group of MHV.
      Extensive collaterals between the hepatic veins and the portal veins appeared in
      the periphery of involved liver lobe in the stricture group of MHV. The levels of
      endotoxin and TXB(2)/6-Keto-PGF1alpha in the blood of portal vein obviously
      increased in the ligation group of MHV and also increased in the stricture group
      of MHV. The levels of endotoxin and TXB(2)/6-Keto-PGF1alpha in the blood of
      portal vein in the ligation and stricture group of MHV were apparently higher
      than those in the ligation group of segmental hepatic vein and in the control
      group. CONCLUSION: The involved liver tissue can not tolerate complete MHV
      occlusion. The hepatic tissue lacking of MHV drain not only loss its function,
      but also cause endotoxemia and disorder of hepatic microcirculation. The involved
      hepatic lobe after the MHV ligation should have been resected at the same time.

PMID- 11825431
TI  - [The effect of detrusor instability secondary to benign prostatic hypertrophy on
      the density of acetylcholinesterase-containing nerves].
AB  - OBJECTIVE: To study the effect of detrusor instability secondary to benign
      prostatic hypertrophy (BPH) on the density of cholinesterase-containing nerve in
      detrusor samples. METHOD: Our present study included 3 groups confirmed by
      urodynamic evaluation. They were control group (8 cases), obstructive detrusor
      stability group (7), and obstructive instability group (12). The specimens were
      obtained from the dome of bladder. The AchE-containing nerves were demonstrated
      by the method of Karnovsky-Roots staining and AchE silver staining. The density
      of AchE containing detrusor nerves in specimens was examined with sterologic
      techniques. RESULT: The density of AchE-containing nerves in the obstructive
      detrusor instability group and the stability group was significantly decreased as
      compared with the control group (P < 0.01). The density of AchE positive nerves
      were also significantly decreased in the obstructive instability group as
      compared with the obstructive stability group (P < 0.05). CONCLUSION: Detrusor
      instability secondary to BPH obstruction is related to the decrease of
      cholinergic innervation density in the detrusor muscles.

PMID- 11825432
TI  - [Expression of nm23 in gastrointestinal smooth muscle tumors and its relation to
      cell proliferative activity].
AB  - OBJECTIVE: To determine the relationship between nm23 expression and benign or
      malignant degree, metastasis, prognosis and cell proliferative activity of
      gastrointestinal smooth muscle tumors (GISMT). METHOD: 86 cases of GISMT were
      studied, and nm23 was detected by the immunohistochemical staining S-P method.
      The cell proliferative activity was evaluated by the silver colloid method for
      argyrophilic nucleolar organizer regions proteins (AgNORs) and by the
      immunohistochemical staining S-P method for proliferating cell nuclear antigen
      (PCNA). RESULT: The expression of nm23 declined significantly according to the
      following order: leiomyomas, low malignant leiomyosarcomas, high malignant
      leiomyosarcomas (P < 0.01). The expression of nm23 was associated with the tumors
      with or without contiguous organ invasion or distant metastasis, the size of
      tumors, the tumors with or without center necrosis (P < 0.01 or P < 0.05). The
      five-year survival rate was significantly higher in patients with nm23 positive
      expression than that with nm23 negative expression (P < 0.05). The expression of
      AgNORs and PCNA with nm23 negative cases was obviously higher than that with nm23
      positive cases (P < 0.01). CONCLUSION: nm23 is a valuable indicator for the
      biological characteristics of GISMT. nm23 expression and cell proliferative
      activity can supply a deficiency each other in distinguishing malignant from
      benign tumors, judging the malignant degree, and predicting the prognosis of the
      patients with GISMT.

PMID- 11825433
TI  - [The detection of breast carcinoma micrometastases in axillary lymph nodes by
      reverse transcriptase-polymerase chain reaction].
AB  - OBJECTIVE: To detect tumor micrometastases in axillary lymph nodes of breast
      carcinoma so as to obtain more reliable information about nodes status and its
      clinical significance. METHOD: The expression of CK19 mRNA was measured in 61
      axillary lymph nodes (LNs) of 15 breast carcinomas by using reverse transcriptase
      polymerase chain reaction (RT-PCR). RESULT: CK19 mRNA expression was detected in
      all 15 breast carcinomas, but not in 5 control LNs. Of 61 axillary LNs analysed
      by HE staining and CK19 RT-PCR, 7 LNs were found to have metastases by
      histological staining and CK19 RT-PCR. Of the remaining 54 axillary nodes, 12
      were found to have metastases by using CK19 RT-PCR method. CONCLUSION: The CK19
      RT-PCR method is more sensitive than histological study for the detection of
      micrometastases in LNs (P < 0.01). This new method is of value in differentiating
      breast cancer patients at high risk for relapse from those with negative lymph
      node.

PMID- 11825434
TI  - [Effect of somatostatin on portal and hepatic hemodynamics and portal venous
      pressure in cirrhotic patients with portal hypertension].
AB  - OBJECTIVE: To investigate the effect of somatostatin on hepatic and portal
      hemodynamics and portal venous pressure in cirrhotic patients with portal
      hypertension. METHOD: Colorful doppler ultrasonography was used to measure the
      diameter and maximum hemokinetic velocity of portal vein and hepatic vein before
      and after intravenous administration somatostatin, and thus their hemokinetic
      volume was calculated respectively. Among 15 surgical patients, changes of the
      portal venous pressure were observed via a catheter before and after the
      administration of somatostatin. RESULT: One hour and 1.5 hour after the
      administration, the pressure of portal vein significantly decreased from 2.77 +/-
      0.26 kPa to 2.42 +/- 0.27 kPa and 2.40 +/- 0.27 kPa, respectively (P < 0.01). The
      systolic pressure, diastolic pressure and heart rate showed no significant
      changes. After the administration, the sectional area of portal vein decreased by
      7.28% but without significance. The maximum hemokinetic velocity of portal vein
      significantly decreased by 18.96% (from 19.72 +/- 7.75 cm/sec to 15.98 +/- 7.26
      cm/sec, P < 0.01). The mean total hemokinetic volume increased from 1786.22 +/-
      926.37 ml/min to 1836.17 +/- 844.24 ml/min, but without significance (P > 0.05).
      CONCLUSION: Continuous instillation of somatostatin via peripheral vein can
      decrease the portal venous pressure in cirrhotic patients with portal
      hypertension. The mechanism may be the decrease of hemokinetic volume caused by
      the decrease of hemokinetic velocity of the portal vein.

PMID- 11825436
TI  - [Management of true extremity aneurysms: experience in 23 patients].
AB  - OBJECTIVE: To explore the etiologic feature and specificity of diagnosis and
      treatment in true aneurysms of the extremities. METHOD: 23 patients with true
      aneurysms of the extremities from January 1984 to September 1997 were
      retrospectively reviewed. RESULT: Of 30 true aneurysms of the extremities,
      multiple aneurysms were found in 7 patients (30.4%). The multiple aneurysms were
      diagnosed in the same time or in different time. 21 patients were treated by
      exclusion of aneurysm and replacement with autogenous saphenous vein or graft.
      CONCLUSION: Early diagnosis and treatment are recommended to prevent
      complications which can cause limb loss, and multiple aneurysms must be taken
      into account. Importance of arteriography should be stressed in the diagnosis of
      multiple aneurysms. Exclusion of aneurysm and autogenous saphenous vein
      reconstruction is the first choice of treatment, circulation of the operated
      extremities should be noticed and close follow-up is imperative to pay attention
      to the development of new aneurysms.

PMID- 11825435
TI  - [Resection of small primary liver cancer: clinical analysis of 82 cases].
AB  - OBJECTIVE: To determine which clinicopathologic features and surgical modalities
      are related to the prognosis of small primary liver cancer (SPLC). METHOD: Eighty
      two patients who had under gone operations for SPLC (<or= 5.0 cm in diameter)
      from 1988 to 1995 were retrospectively studied. 60 patients were HBsAg positive,
      and 71 patients suffered from liver cirrhosis. Bisegmentectomy, segmentectomy and
      partial resections were performed in 13, 14 and 55 patients separately. RESULT:
      The overall operative mortality was 1.2%, and the 1-, 3-, 5-year survival rates
      were 92.7%, 72.5% and 54.3%, respectively. The 5-year survival rates of 78
      patients with hepatocellular carcinoma according to histologic features were
      79.6%, 49.9% and 41.1% in well-differentiated (15 patients), moderately (53), and
      poorly differentiated (10) groups. Recurrence and metastasis rates in 1, 3, 5
      years were 12.8%, 40.7% and 71.5%, separately. CONCLUSION: SPLC has the same
      history of large PLC. Early diagnosis and limited hepatic resection are very
      important to decrease the mortality and increase the survival rate.

PMID- 11825437
TI  - [Extra-anatomy axillary-femoral or femoro-femoral bypass grafting for the
      treatment of aorta-iliac occlusive disease].
AB  - OBJECTIVE: To study the result of extra-anatomy axillary-femoral or femoro
      femoral bypass grafting which was performed to treat aorta-iliac arterial
      occlusive disease. METHOD: From 1978 through 1997, 32 patients with aorta-iliac
      occlusive disease underwent extra-anatomy axillary-femoral or femoro-femoral
      bypass grafting at our hospital. Eighteen patients with aorta or bilateral iliac
      artery occlusive lesion underwent axillary-femoral artery bypass, including
      axillary-bifemoral artery bypass (2 patients). Fourteen patients with one side
      iliac arterial occlusive lesion received femoro-femoral bypass grafting. In who
      had had axillary-femoral artery bypass 18 patients, 8 received, pure silk
      prosthesis, and 10 Gore-Tex prosthesis. In femoro-femoral arterial bypass, pure
      silk prosthesis was given to 8 patients, saphenous vein to one, and Gore-Tex
      prosthesis to 7. RESULT: Follow-up for 5 years, a patency rate of 78% was
      achieved in femoro-femoral artery bypass, in which no different patency rate was
      found between pure silk prosthesis and Gore-Tex prosthesis. In axillary-femoral
      bypass, eight pure silk prostheses were occluded after 5-year follow-up. One of
      10 Gore-Tex prostheses was occluded, and false aneurysm in groin was found in
      another patient. CONCLUSION: This operation is easy and safe, it has less damage
      and no abdominal complication. The recovery of the patient is quick. Pure silk
      prostheses are only used in short segment femoro-femoral bypass grafting.

PMID- 11825438
TI  - [Primary ileocecal lymphoma: report of 30 cases].
AB  - OBJECTIVE: To investigate the best therapeutic method for primary ileocecal non
      Hodgkin's lymphoma. METHOD: Clinicopathologic features of 30 patients who had
      been treated from June 1964 to September 1993 were analyzed retrospectively.
      RESULT: Twenty-eight patients (93%) underwent resection of their disease. Eleven
      patients had the resection followed by chemotherapy. Eleven patients had the
      resection followed by chemotherapy and radiotherapy. All had pathologic evidence.
      Twenty-nine patients were categorized as B-cell type NHL. One had T-cell lesion.
      Eleven patients had stage I disease, 11 stage II, 4 stage III, and 4 stage IV.
      The 5-year survival rate was 36.67%. CONCLUSION: The prognostic factors are stage
      of the disease and treatment modality. Adequate initial surgery combined with
      radiotherapy and chemotherapy may provide optimum therapy for patients with
      primary ileocecal lymphoma.

PMID- 11825439
TI  - [Unreamed interlocking intra medullary nailing in treating tibial and fibular
      fractures].
AB  - OBJECTIVE: To report the experience in the use of unreamed interlocking
      intramedullary nails. METHOD: From 1995 to 1997, 54 tibial and fibular fractures
      were treated with unreamed interlocking intramedullary nails they included open
      fractures (9 cases) and close fractures (45). RESULT: All fractures healed within
      6 months and showed good knee and ankle joint functions. Slight postoperation
      infection was found in one of the open fractures. Incomplete injury of peroneal
      nerve was noted in 1 case. CONCLUSION: Unreamed interlocking intramedullary nail
      can be used to treat diaphyseal fractures effectively. It can protect the soft
      tissue envelope around the fracture and prerent local blood supply from further
      damaginge.

PMID- 11825440
TI  - [Surgical treatment of infective endocarditis].
AB  - OBJECTIVE: To summarize the experience of surgical treatment of infective
      endocarditis in 28 patients. METHOD: Open heart surgery under cardiopulmonary
      bypass was performed in all patients: valve replacement (24), VSD repair and
      tricuspid annuloplasty (3), and Bentall (1) 17 mechanical and 7 homograft valves
      were placed. RESULT: Two died in hospital, 4 died from infection, 1 had
      periprosthetic leakage and incompetence respectively. 22 survivors showed
      improved heart function. CONCLUSION: Combined medication and surgical treatment
      is superior to antibiotic treatment in long-term survival and convalescence.
      Infective reccurrence, reinfection and advanced heart failure are major risk
      factors after operation.

PMID- 11825441
TI  - [Direct vision mitral valve reconstruction: a long-term follow-up of 46 cases].
AB  - OBJECTIVE: To improve the long-term results of direct vision mitral valve
      reconstruction. METHOD: From July 1983 through July 1995, 46 patients with mitral
      valve disease were treated by a direct vision reconstructive techniques.
      Rheumatic valve stenosis and incompetence were noted in 39 (patients),
      nonrheumatic insufficiencies in 5, and congenital disease in 2. According to
      leaflet pliability, type I normal leaflet motion was notedin 17 patients, type II
      leaflet prolapse in 3 and type III restricted leaflet motion in 29. Cardiac
      function (NYHA classification) showed class II in 2, class in 25 III, and class
      IV in 19. Valvuloplasty and annuloplasty were performed with various techniques
      according to the pathanatomical changes of the valve. Prosthetic obturators self
      made were employed in 29 patients. RESULT: The operative mortality rate was 6%
      (3/46). In the mitral valve replacement group it was 10% (27/265). Two to 10
      years (mean 65 months) follow-up showed grade I cardiac function in 6 patients,
      grade II in 17, grade III in 8, and grade IV in 3. CONCLUSION: Good long-term
      results can be achieved by valve reconstruction with lower mortality and
      incidence of thromboembolism than.

PMID- 11825442
TI  - [Gliosis: follow-up and pathological study of 34 cases].
AB  - OBJECTIVE: To discuss the etiology, clinical characteristics, pathology and
      canceration in gliosis. METHOD: 34 cases of gliosis were analyzed retrospectively
      follow-up for a long period. Their pathologic slices were restudied. RESULT: The
      causes of gliosis included cranial infection, specially infection caused by virus
      without distinct symptoms cerebral ischemia, brain injury, radiological treatment
      of brain. most cases showed symptoms of intracranial hypertension, 55.9% of the
      patients accompanied with epilepsy. Pathological examination revealed
      proliferation of small gliosis in all cases, lligodendrogliosis in 79.4% of the
      cases. The cases with proliferation had better rehabilitation. Canceration was
      noted in 11.8% of all cases. CONCLUSION: Gliosis is a nonmalignant disease,
      however, it has the possibility of canceration.

PMID- 11825444
TI  - [Inhibitor of plasminogen activator 1 (PAI-1) in hepatocellular carcinoma].
AB  - OBJECTIVE: To study the expression of the type-1 inhibitor of plasminogen
      activator (PAI-1) on protein and mRNA in hepatocellular carcinoma (HCC), and the
      relation between PAI-1 and biological behaviour of HCC. METHOD: The tumor
      specimens of HCC (n = 48) and benign liver tumor (contorl n = 12) were tested by
      immunohistochemistry for the expression of PAI-1 protein. The tumor specimens of
      HCC (n = 20) and normal liver tissue (contorl n = 5) were evaluated by Northern
      blot analysis for the expression of PAI-1 mRNA. RESULT: PAI-1 protein and PAI-1
      mRNA were higher in tumor cell than in the marginal tissue of tumor and in
      control (P < 0.01 and P < 0.05). In deaths 2 years after surgery, PAI-1 was
      increased as compared to the survival group (P < 0.05). When negative PAI-1
      conupared with positive urokinase-type plasminogen activator (uPA) and positive
      uPA receptor (uPAR). The nambeigs invasion case increased, the difference was
      more significant than that in the group with negative PAI-1, uPA and uPAR (P =
      0.039). CONCLUSION: The expression of PAI-1 protein and PAI-1 mRNA is increased
      in HCC. PAI-1 contributes to the invasion, metastasis and prognosis of HCC.

PMID- 11825443
TI  - [Carboplatin drug concentration in tumor tissues by intraperitoneal
      chemotherapy].
AB  - OBJECTIVE: To investigate drug concentration in tumor tissues after
      intraperitoneal chemotherapy with carboplatin. METHOD: High performance liquid
      chromatography was used to study the pharmacokinetics of carboplatin in 10
      patients with resectable advanced gastric cancer after intraperitoneal
      chemotherapy. 300 mg/m(2) carboplatin in 750 ml 0.9% sodium chloride were
      intraperitoneally injected. After 160 - 180 minutes, peritoneal fluid, blood of
      portal vein and peripheric blood were collected. 240 - 270 minutes later, cancer
      tissues, normal tissues, peritoneum, omentum, and normal lymph nodes were taken.
      The total carboplatin concentrations were measured. RESULT: Drug concentration
      was highest in the peritoneal fluid, followed by that the in blood of portal
      vein. They were 8 times, 1.6 times of the concentration in peripheric blood. The
      concentration in the peritoneum was higher than in other tissues (P < 0.05). The
      concentration in tumor tissues was higher than that in normal tissues.
      CONCLUSION: Intraperitoneal chemotherapy with carboplatin chemotherapy increased
      its concentration in the peritoneal cavity and the blood of portal vein, and its
      accumulation in the peritoneum and tumor tissues, which help eliminate
      subclinical lesions, improve clinical stage, control iatrogenic metastasis, and
      increase resectable rate.

PMID- 11825445
TI  - [Association of nm23-H1 with orthopedic oncological conditions].
AB  - OBJECTIVE: To explore the correlation between nm23-H1 gene and malignant and semi
      malignant bone tumors. METHOD: Thirty surgical specimens were collected,
      including 8 osteosarcomas, 7 giant cell tumors, 4 chondrosarcomas, 2 Ewing's
      sarcomas, 2 malignant fibrohistocytomas, 1 neurofibrosarcoma, 1 schwannoma, and 5
      metastatic cancers. The expression of nm23-H1 in these specimens was observed by
      in situ hybridization and immunohistochemical staining. RESULT: The expression of
      nm23-H1 in 4 cases of primary giant cell tumor (GCT) was high, but was low or
      absent in 3 recurrent ones. In 4 cases of chondrosarcomas, the expression was
      positive. Its expression was basically negative in Ewing's tumor, malignant
      fibrous histiocytoma and metastatic sarcomas. CONCLUSION: There is no association
      of nm23-H1 with osteosarcoma.

PMID- 11825446
TI  - [Diagnostic value of serum creatine kinase MB in patients with cardiac damage
      after electric injuries].
AB  - OBJECTIVE: To investigate the incidence of cardiac damage and the diagnostic
      value of serum myocardial enzyme following electric injuries. METHOD: 32 patients
      with electrical contact injuries were evaluated by serial electrocardiograms
      (ECG), creatine kinase (CK) and creatine kinase MB isoenzyme (CK-MB)
      determinations. The patients were divided into two groups according to the ECG.
      RESULT: 17 patients showed abnormal ECG (Group A), and 15 normal ECG (Group B).
      Positive correlations were noted between CK, CK-MB and the size of electric
      burns. The difference of serum CK-MB and 1.1% of total CK (CK-MB in skeletal
      muscle) was defined as CK-MB difference. CK, CK-MB, CK-MB/total CK ratio and the
      CK-MB difference were significantly higher in group A than in group B (all P <
      0.05). The CK-MB difference of 88% (15/17) patients in group A was more than 25
      U/L, whereas that was 6.7% (1/15) in group B (P < 0.01). Six patients with CK-MB
      difference greater than 100 U/L had obvious cardiac damage. CONCLUSION: Cardiac
      damage is a common complication of electric injuries. The cardiac damage could be
      estimated by serum CK-MB, particularly by the CK-MB difference. The CK-MB
      difference might be a useful indicator for evaluating the severity of the cardiac
      damage.

PMID- 11825447
TI  - [Apoptosis and expression of PCNA in superficial transitional cell bladder cancer
      as related to recurrence].
AB  - OBJECTIVE: To determine the expression of apoptosis and PCNA in superficial
      transitional cell bladder cancer and to evaluate its significance as a recurrence
      marker. METHOD: 87 cases of superficial transitional cell bladder cancer were
      analysed for the expression of apoptosis and PCNA by using the 3-end labeling
      method of DNA and immunohistochemical staining in tissue sections. The apoptotic
      indexes and PCNA indexes were respectively the percentages of apoptotic cells or
      PCNA positive cells among tumor cells. RESULT: The end labeling method allowed a
      precise evaluation of the expression of apoptosis. Apoptosis occurred in 89.6% of
      superficial transitional cell bladder cancer. In 17 patients who suffered from
      tumor recurrence, the ratio of apoptosis indexes to PCNA indexes was
      significantly higher than that in those without recurrence (P < 0.01).
      CONCLUSION: The ratio of apoptosis indexes to PCNA indexes was believed to be
      related to tumor recurrence and might be of value in the assessment of recurrence
      of superficial transitional cell bladder cancer.

PMID- 11825448
TI  - [The influence of side-to-side portacaval shunt plus enhancement of perfusion of
      hepatic artery on cirrhotic liver: an experimental study].
AB  - OBJECTIVE: To for improving the perfusion of liver, we designed an operation of
      portacaval shunt (PCS) plus enhancement of perfusion of hepatic artery (EPHA).
      METHOD: 48 wistar rats were divided into 4 groups randomly. group I (normal
      control), group II (liver cirrhotic control), group III (PCS on liver cirrhosis),
      and group IV (PCS + EPHA on liver cirrhosis). The EPHA was performed by the
      ligation of the left gastric and splenic artery. Liver function tests, liver
      biopsy, and nuclide hepatobiliary dynamic imaging (NHDI) were performed on the
      2nd week and the 6th month after operation. RESULT: In NHDI, the peak time was
      short (P < 0.05) and the excretive rate was high (P < 0.01). The liver function
      and the proliferative degree of the fibrotic tissue of the liver were perfected
      significantly (P < 0.05) in the group IV compared with the group III after
      operation. CONCLUSION: PCS + EPHA can increase the perfusion of the hepatic
      artery, maintain the liver function and delay liver cirrhosis, and overcome the
      side effects of PCS. It is a new surgical technique in treating portal
      hypertension.

PMID- 11825449
TI  - [Repair of articular cartilage defect with a large area: an experimental study].
AB  - OBJECTIVE: To compare and evaluate potentialities and biological characteristics
      of grafts of chondrocytes cultured on fascia, periosteum and articular cartilage
      in repairing large defects of articular cartilage. METHOD: The large defects of
      articular cartilage were repaired with grafts of freeze-stored and fresh
      chondrocytes cultured on fascia, periosteum and articular cartilage, which were
      evaluated by a number of observation methods. RESULT: The fresh and freeze-stored
      fascial chondrocytes were superior to free grafts of chondrocytes in potentiality
      of formation of new cartilaginous tissue, structure and metabolism of newly
      formed tissue. Relatively good results were also obtained similarly by using
      fresh autografts of periosteum and cartilage. CONCLUSION: Chondrocytes can be
      cultured normally on fascia, which can be regarded as an ideal carrier of
      chondrocytes.

PMID- 11825450
TI  - [Culture of chondrocytes seeded onto chitin scaffoldings coating with different
      materials: experimental study].
AB  - OBJECTIVE: To find the possibility of chitin used as scaffolds in tissue
      engineering. METHOD: Chondrocytes were cultured when they were seeded onto chitin
      meshcoated with polylactic acid (PLA) lecithin (LEC) and poly-l-lysine (PLYS).
      With light microscope and scanning electron microscope, the scaffolds in
      hydrophilia and absorptivity to chondrocytes and the function of the cells were
      observed. RESULT: LEC can change the hydrophilia of scaffolds. PLYS can
      strengthen the absorptivity of the scaffolds. and promote the matrices production
      of chondrocytes. CONCLUSION: The chitin coated with LEC and PLYS can be used as
      scaffolds in tissue engineering.

PMID- 11825452
TI  - [The treatment of rat fulminant hepatic failure by auxiliary partial heterotopic
      liver transplantation: experimental study].
AB  - OBJECTIVE: To confirm the effect of auxiliary partial heterotopic liver
      transplantation (APHLT) in the treatment of fulminant hepatic failure (FHF).
      METHOD: On 30 rat models of FHF, 62% of partial liver grafts were implanted below
      the host residual liver with 28 successful operations. The survival rate,
      biochemical test for liver function, (99m)Tc-HIDA liver scintigraphy and
      pathological changes of the grafts and host livers were studied. RESULT: The
      survival rate in 48 hours was 71.4% compared with 0% in 15 FHF animals. 14 days
      after the operation, the host liver regenerated obviously and the liver function
      recovered while the graft shrank gradually. 30 days later, the graft became
      fibrosis completely. CONCLUSION: Depending on the temporary function support of
      the graft, the native residual liver could regenerate and restore its function
      while the graft tended to atrophy.

PMID- 11825451
TI  - [Alpha1-adrenoceptor subtypes in rabbit penile corpus cavernosum].
AB  - OBJECTIVE: To study alpha(1)- adrenoceptor (alpha(1)- AR) subtypes with the
      functional role and the distribution of its subtypes in rabbit penile corpus
      cavernosum. METHOD: The rabbit penile corpus cavernosum was studied by using
      functional experiment and radioligand binding assay. RESULT: In the radioligand
      binding assay, the maximal binding capacity (Bmax of (125)IBE and alpha(1)-AR)
      decreased obviously after pretreatment with chloroethylclonidine (CEC), which
      were 746 +/- 236 fmol/mg protein and 214 +/- 71 fmol/mg protein, respectively.
      Alpha(1A)-, alpha(1D)-and alpha(1B)-AR took about 20%, 25% and 55%, respectively.
      In the functional experiments, the maximal contraction induced by norepinephrine
      (NE) was not decreased significantly after pretreatment with CEC. The pA(2)
      values of two alpha(1)-AR selective antagonists, 5-MU, BMY7378, for antagonizing
      NE-induced penile corpus cavernosum contraction had a high correlative
      association with the pK(I) values for cloned alpha(1A)-AR. CONCLUSION: The
      functional alpha(1)-AR subtype is alpha(1A)-AR although there are three subtypes
      in the penile corpus cavernosum.

PMID- 11825453
TI  - [Expression of eNOS and IL-10 gene in signal transduction for liver
      regeneration].
AB  - OBJECTIVE: To detect the effects of eNOS and IL-10 on liver regeneration under
      physiological and pathological condition. METHOD: The rat model of liver
      regeneration was made by partial (70%) hepatectomy. Some rats were injected with
      CCl(4) and performed splenectomy. Hepatocytes DNA replication was tested by flow
      cytometry method (FCM) and the gene expression of eNOS in liver cells were
      analysed using RT-PCR. The IL-10 gene expression in liver cells was shown by Dot
      Blot hybridization method. The synthesis and distribution of IL-10 protein in
      liver tissue were examined by immune histochemical and morphometric method.
      RESULT: The expression of eNOS gene promoted liver regeneration while the
      expression of IL-10 gene inhibited it. CONCLUSION: eNOS and IL-10 play an
      important immunomodulatory role in liver regeneration under physiological or
      pathological conditions. The effects of eNOS and IL-10 on liver regeneration
      differ and they show an opposite modulatory effects on liver regeneration. Such
      effects are affected by spleen and general immune system.

PMID- 11825454
TI  - [Dynamic change of androgen-receptor in tumor and surrounding liver tissue of
      nude mice model with transplanted human HCC].
AB  - OBJECTIVE: To research into the law of androgen-receptor (AR) dynamic change in
      developing course of human HCC. METHOD: Dynamic measurement of AR in tumor and
      peritumorous tissue was performed in nude mice model with orthotopic transplanted
      human HCC. RESULT: Tumor nodules were present in 90% nude mice 4 weeks after
      transplantation, tumor necrosis was found in the 10th week, and remarkable
      necrosis occurred in the 12th week. The quantity of AR in tumor and peritumorous
      tissue was highest in the early stage of tumor (102.32 +/- 21.42 fmol/mg protein
      and 72.45 +/- 10.11 fmol/mg protein respectively), and then decreased
      progressively with time to the 10th week (40.98 +/- 21.11 fmol/mg protein and
      53.39 +/- 7.01 fmol/mg protein respectively). The difference in AR between each
      two weeks was significant. CONCLUSION: Androgen promotes the development of tumor
      because of existence of AR, and its action may decline after establishment of
      tumor. Therefore, antiandrogen treatment may be ineffective after establishment
      of tumor.

PMID- 11825455
TI  - [Clinicopathologic factors influencing the serum of interleukin-12 level of
      patients with PHC: multivariate statistical analysis].
AB  - OBJECTIVE: To investigate clinicopathologic factors influencing the serum of IL
      12 level of patients with PHC. METHOD: Serum interleukin-12 (IL-12) level was
      determined by ELISA in 16 patients with primary hepatic carcinoma (PHC). The
      following clinicopathologic factors were considered for the serum IL-12 effect:
      age, serum albumin and serum total bilirubin, size of tumor, number of tumor,
      tumor thrombus of portal vessels (present or absent), time of operation, tumor
      resected (yes or no), histological grade of tumor, and the amount of lost blood
      during operation. Dependent variables were serum IL-12 level at 1 day before
      operation and at 1 and 7 days after operation. The multivariate results were
      confirmed using multiple regression analysis. RESULT: Size of tumor and serum
      albumin greatly affected serum IL-12 level before operation. Serum total
      bilirubin and age affected serum IL-12 level. It was significantly different
      before and after operation, because of the amount of lost blood. CONCLUSION: The
      main effective factors of serum IL-12 level were size of tumor and the hepatic
      function of patients. Operative trauma was the major factor reducing IL-12 level
      after operation.

PMID- 11825456
TI  - [p53 gene mutation in hepatocellular carcinoma].
AB  - OBJECTIVE: To study the relationship between mutation of p53 gene and
      hepatocellular carcinoma (HCC). METHOD: Sixty-five cases of HCC from Nanning
      prefecture of high aflatoxin (AFB1) exposure were studied by polymerase chain
      reaction and restrictive fragment length polymorphism (PCR-RFLP) analysis to
      examine the exon 7 of p53 gene in HCC. RESULT: 58.5% of the cases were found to
      show mutation at codon 249 of p53 gene; 63.6% for the HCCs with HBsAg negative,
      and 57.4% for those with HBsAg positive; 88.9% for those with metastasis, and
      46.8% for those with no metastasis. The mutation rate of p53 gene was 10.0%,
      55.2% and 80.8% in the well-, moderately- and poorly-differentiated HCC
      respectively. CONCLUSION: AFB1 is the most important agent for the mutation at
      the hot-spot, and hepatitis B virus is the synergistic risk factor. Further study
      indicated that the p53 gene mutation is correlated with the differentiation and
      the metastasis of HCC and may serve as an important prognostic factor.

PMID- 11825457
TI  - [Retrograde partial hepatectomy: report of 11 patients].
AB  - OBJECTIVE: To study a new approach to hepatectomy for liver tumors resected
      difficulty by typical method. METHOD: The operative order is retrograde as
      compared with typical hepatectomy, namely, transection of the liver is performed
      first, isolating adhesions between the tumor and the diaphragm or partial invaded
      phrenectomy is performed second, and then after cutting corresponding ligaments,
      liver tumor is removed. If the surrounding organs were invaded or adhered by
      tumor too tightly to be separated. They were resected with the tumor. RESULT: The
      approach was used in 11 patients with malignant tumors of liver from June 1994 to
      January 1996. Operation time was 192 min (150 - 250 min) and estimated blood loss
      during operation was 1460 ml (800 - 4, 200 ml). No operative mortality was found
      and all of the patients recovered uneventfully. CONCLUSION: The retrograde
      partial hepatectomy is a good method for resection of liver tumors resected
      difficulty by typical hepatectomy.

PMID- 11825458
TI  - [Development and clinical application of a brain stereotactic endoscope].
AB  - OBJECTIVE: To investigate the feasibility, indications and advantages of
      endoscopic surgery for brain neoplasms and hypertensive haematoma. METHOD: A self
      designed brain endoscope with a wide working channel was used for resection of
      deep-seated brain neoplasm or other cranial cerebral operations of 30 patients
      operated on endoscopically, 13 had intracranial tumor, 15 hypertensive
      intracerebral haematoma, 1 thalamic abscess, and 1 cysticercosis. RESULT: Total
      removal of tumor was achieved in 4 patients, subtotal or major partial removal in
      7, and biopsy in 2. Completely evacuation of haematoma was achieved in 7 patients
      and partial evacuation in 8 (over 80%). The abscess was evacuated and the
      solitary cysticercosis focus was removed with our endoscope. No obvious
      postoperative complications were noted. CONCLUSION: The advantages of
      stereotactic endoscopy for deep-seated brain neoplasm include accurate
      intraoperative localization, minimal invasion, good recovery, no or a few
      complications. The indications for this intervention are small lesions deep in
      the brain parenchyma with well-defined boundary and light vascularity.
      Intracerebral haematoma can be evacuated under direct vision endoscopically,
      without damage to the haematoma cavity wall.

PMID- 11825459
TI  - [Surgical treatment of the hypopharyngeal and cervical esophageal carcinoma].
AB  - OBJECTIVE: To review the experience of surgical treatment of hypopharyngeal and
      cervical esophageal carcinoma. METHOD: Seventy-six patients with squamous-cell
      carcinoma of the hypopharynx and cervical esophagus underwent surgery in our
      department from 1980 to June 1997. The site of the tumour was in hypopharynx in
      31 patients and in cervical esophagus in 45. RESULT: The resectability rate of
      hypopharyngeal carcinoma (HPC) was 98.6% (30/31). The types of the esophageal
      reconstruction included pharyngo-esophageal anastomosis (3 patients)
      platysmamyocutaneous flaps reconstruction (PMFR) (12) free jejunal interposition
      (3) and gastric tube transposition following total pharyngolaryngo esophagectomy
      (12). The resectability rate of cervical esophageal carcinoma (CEC) was 91%
      (41/45). The esophageal construction applied gastric tube after esophagectomy
      without thoracotomy except one. The postoperative morbidity was 36.5% for gastric
      tube reconstruction (including one died of heart failure), 33.3% (1/3) for free
      jejunal interposition and zero for PMFR. The overall follow-up was from 2 to 108
      months (median: 56.5 months) and the 1-, 3-, 5-year survival rates were 79.3%,
      60% and 31.6% respectively for HPC and 68.3%, 9.5%, 0% respectively for CEC.
      CONCLUSION: Our data demonstrated that the resectability rate of the HPC and CEC
      was quite high but the long-term result of HPC was better than that of CEC. The
      PMFR after pharyngolaryngo-cervicalesophagectomy was a safe, effective operation
      with low morbidity and excellent long-term results.

PMID- 11825460
TI  - [The clinical effect of ATG and OKT3 on the treatment of refractory rejection
      after cadavaric kidney transplantation].
AB  - OBJECTIVE: To observe the effect of ATG and OKT3 on the treatment of refractory
      rejection, including acute and chronic rejection after cadaveric kidney
      transplantation. METHOD: 87 patients with refractory rejection after cadaveric
      kidney transplantation were treated by using ATG (13 patients) and OKT3 (74). A
      total dose of 1 000 mg for ATG group or 45 mg for OKT3 group was administered for
      each patient. RESULT: Two accelerating rejection and acute rejection were
      reversed and 7 in the ATG group, 90.00% (27/30) and 90.47% (38/42) in the OKT3
      group respectively. A significant difference of total reverse rates was seen
      between the ATG and OKT3 groups (69.23% verse 90.28%, P < 0.05). In retransplant
      patients, the reverse rate of acute rejection by OKT3 was 91.67% (11/12). But
      OKT3 did not show any effect in patients with chronic rejection. CONCLUSION: OKT3
      is better than ATG for reversing the refractory rejection, especially in
      retransplant patients, but it has no any effect on chronic rejection.

PMID- 11825461
TI  - [Application of stress urethral pressure profile for diagnosis and treatment of
      stress incontinence].
AB  - OBJECTIVE: To apply the stress urethral pressure profile (SUPP) to diagnose the
      genuine stress incontinence (GSI) and to evaluate the results of treatment.
      METHOD: 22 patients with GSI underwent SUPP and rest urethral pressure profile
      (RUPP) using Dantec Menuet. RESULT: The results showed that the pressure
      transmission ratio (PTR) was 0.68 +/- 0.06, and urethral close pressure (UCP) was
      -0.62 +/- 0.22 kPa in 22 patients. PTR and UCP raised significantly after
      operation in 5 patients, P < 0.01. The results of SUPP were compared with those
      RUPP. CONCLUSION: SUPP is important in both diagnosis and evaluation of GSI,
      although some limitation exists. To improve the level of diagnosis, it should be
      combined with other method in clinical use.

PMID- 11825462
TI  - [Pathophysiology and surgical treatment on Relaxed Pelvic Floor Syndrome].
AB  - OBJECTIVE: To study the pathophysiology of the "Relaxed Pelvic Floor Syndrome
      (RPFS)" and to assess the value of the "Pelvic Cavity Fixation Operation (PCFO)"
      for the syndrome. METHOD: 11 patients, who were diagnosed as having RPFS,
      underwent standardized PCFO. All the patients were followed for a mean time of 19
      months (5 - 72 months). RESULT: The main syndromes and signs included difficulty
      in defecation, inability to empty the rectum properly, fullness of perineum,
      protrusion of perineum at bearing down, back-inclining uterus, relaxation of the
      rectum on digital examination. The anorectal dynamics showed that the sequence
      pressure and rest pressure of the anal cannel were lower and the time of
      contraction of the anal cannel decreased than that of the normal controls. The
      rectum sensation was damaged slightly. Defeacography showed that there were
      relaxing changes in several systems in the pelvic cavity. Operatively, it was
      easy to see the relaxation of the supporting structure of the colon, rectum,
      uterus and the lower position of the peritoneal cavity. PCFO has achieved good
      results. Seven patients were free of symptoms completely and 4 improved.
      CONCLUSION: The relaxing changes of the supporting tissue of many viscus fefer to
      several systems are the pathophysiologic of the RPFS. "Pelvic Cavity Fixation
      Operation" is useful in the treatment of the syndrome.

PMID- 11825463
TI  - [Surgical treatment of aortopulmonary septal defect].
AB  - OBJECTIVE: To study the surgical treatment of aortopulmonary septal defect.
      METHOD: From January 1983 to December 1996, 5 patients with aortopulmonary septal
      defect (APSD) (2 male and 3 female) aged from 6 to 34 years (mean 17.4 years)
      underwent surgical treatment. According to Mori's were classification, 5 patients
      belonged to type I, 2 type II and 1 type III. The diameters of the defect ranged
      from 1.0 to 3.0 cm. The operations were performed under moderate hypothermic
      cardiopulmonary bypass. Pulmonary artery incision was performed, in 3 patients
      while aortic incision in the other 2. All defects were repaired by Dacron patch.
      RESULT: There were no operative deaths and postoperative complications. During
      follow-up of 10 months to 12 years, no late complications and deaths were found.
      CONCLUSION: The operation should be done early as possible whenever the diagnosis
      is established. The surgical repair should be taken under cardiopulmonary bypass.
      To chose an incision on the aorta is more reasonable than on the pulmonary
      artery. The use the dacron patch can prevent stenosis and recanalization after
      operation.

PMID- 11825464
TI  - [Correlation between accumulation of (99m)Tc-MIBI in breast cancer or benign
      lesion, cell proliferation and angiogenesis].
AB  - OBJECTIVE: To study the accumulation of (99m)Tc-MIBI in breast cancer or benign
      lesions and the correlation between cell proliferation and angiogenesis. METHOD:
      (99m)Tc-MIBI positive imaging was performed on 38 patients with palpable breast
      mass. A ratio of radioactivity value of mass to normal tissue was assessed 10
      minutes after injection of (99m)Tc-MIBI in posterior oblique view. Cell
      proliferation and angiogenesis were assessed by immunostaining of proliferating
      cell nuclear antigen (PCNA) and ulex europaeus I lectin (UEA- I). Data were
      analyzed by T-test, correlation and regression analysis. RESULT: We studied 17
      true-positive, 5 false-negative, 15 true-negative, and 1 false positive patients
      (chi(2) = 18.74, P < 0.001). In patients with positive (99m)Tc-MIBI scans, the
      diameter of mass (4.00 +/- 1.95 cm) was larger and the percentage of PCNA
      positive cell (74.13% +/- 13.84%) was significantly higher than that in patients
      with negative scans (2.14 +/- 1.00 cm, 43.76% +/- 20.78%, P < 0.01). No
      significant evidence of difference between the number of angiogenic vessels of
      the two groups (181.3 +/- 71.7, 138.3 +/- 103.0, P = 0.141). The accumulation of
      (99m)Tc-MIBI was most strongly correlated with the percentage of PCNA positive
      cell (r = 0.56, P = 0.000), but was not related to the number of vessels (r =
      0.31, P = 0.056). In stepwise regression analysis, the variance number of vessels
      was not included in the model. CONCLUSION: The accumulation of (99m)Tc-MIBI in
      breast cancer is an indicator of cell proliferation, and no evident relationship
      with angiogenesis has been found.

PMID- 11825465
TI  - [Histological and electron microscopic study of rotator cuff tear].
AB  - OBJECTIVE: To understand the changes of rotator cuff during tear and observe the
      pathologic and ultramicroscopic structure of rotator cuff. METHOD: Histological
      and ultra thin slides of samples of 36 cases of rotator cuff were made. RESULT:
      The degeneration of rotator cuff happened in synovium side, and then extended to
      the middle and deep sides of tendon. The deep side of cuff tendon could
      degenerate without synovium. The repair of tendon could be achieved with two
      types of healing. CONCLUSION: It would be difficult to achieve full repair when
      complete tear and deep side tear occurred to the rotator cuff.

PMID- 11825466
TI  - [Acetabular dysplasia:an experimental study].
AB  - OBJECTIVE: To demonstrate whether acetabular dysplasia represents a primary
      feature of congenital dislocation of the hip or secondary defect. METHOD: The
      capsule of twelve puppies aged five to nine weeks was incised and the ligamentum
      teres was completely severed under anaesthesia. A part of gluteal medium muscle
      was implanted in the acetabulum and the head of the femur was dislocated from
      acetabulum. Roentagenogram was made three weeks after dislocation in all animals.
      RESULT: As early as three weeks after dislocation, acetabular dysplasia was
      clearly noted in all animals. There was more acetabular obliquity and increase of
      acetabular index. CONCLUSION: The acetabular dysplasia is the result but not the
      cause of congenital dislocation of the hip. This result provides probably support
      for the concept of developmental dislocation of the hip.

PMID- 11825467
TI  - [Surgical injuries influence on release of endothelin-1 and local blood perfusion
      of amputated extremities].
AB  - OBJECTIVE: To observe influence of amputations and surgical injuries on synthesis
      and release of endothelium-derived endothelin-1, and local blood perfusion of
      amputated extremities. METHOD: The plasma endothelin-1 concentrations of 18
      patients preoperatively and postoperatively and the endothelin-1 concentrations
      of femoral artery wall in 80 SD rats were determined using radioimmunoassay
      technique before and after amputation. Local blood perfusion of amputated
      extremities in rats were determined using laser Doppler flowmetry. RESULT: The
      plasma endothelin-1 concentrations in the patients with surgical injuries
      increased obviously, reached peak value at fourth hour postoperatively, being
      approximately 3 times of that of the control group. The endothelin-1
      concentrations of femoral artery wall in amputated rats also increased, reached
      peak value at second hour after amputation, being approximately 2 times of that
      of the control group, and then decreased gradually, at the same time the local
      blood perfusion decreased, reached its lowest value at second hour after
      amputation, being only 25 percent of the control value. The endothelin-1
      concentration of rat femoral artery wall was negatively relative to local blood
      perfusion (r = -0.83). CONCLUSION: Injuries enhance synthesis and release of
      endothelin-1. It is probably one of the main causes of vasospasm after injuries.

PMID- 11825468
TI  - [Memorial metal ball for the treatment of avascular necrosis of femoral head].
AB  - OBJECTIVE: To introduce a new method for the treatment of avascular necrosis of
      the femoral head. METHOD: A technique has been developed what the memorial metal
      ball, and where the graft of the wing of the ilium is harvested with the deep
      circumflex iliac vascular pedicle and implanted into the avascular area of the
      femoral head. This procedure has been performed in 28 hips in 22 patients.
      RESULT: Preoperatively, 8 hips were of Ficat Arlet Stage II and twenty stage III.
      Postoperatively, eighteen patients were pain free, 3 had mild pain, and 1 had
      moderate pain. The radiographic appearance improved in 2 cases. No major
      complications occurred. CONCLUSION: It is one of the better alternatives that can
      prevent the necrotic femoral head from progressing to collapse and promote
      revascularization and new bone formation by direct mechanical support. The
      technique is suitable for the treatment of avascular necrosis of femoral head of
      stage I to III.

PMID- 11825469
TI  - [Classification and related operation procedures of pelvic tumor treated with
      partial pelvic resection].
AB  - OBJECTIVE: To establish a classification system of pelvic tumor in terms of the
      location of lesion in order to project surgical treatment with less extent of
      damage to the affected limb function. METHOD: Thirty-six cases were treated by
      partial pelvic resection with limb salvage, and 20 were followed up. The lesions
      were divided into four groups on the basis of sacral-iliac and/or hip joint
      involved. In group I, lesion was noted in the ischium or pubis only;in group II
      the lesion was located at sacral-iliac joint or hip joint. The patients with
      acetabulum involved were classified into group III both sacral-iliac joint and
      hip joint were destroyed by tumor in group IV. Surgical treatment was designed as
      resection, resection with sacral-iliac joint reconstruction, resection without
      hip joint reconstruction according to the classification of the lesion. The
      patients in group IV were treated with traditional hemi-pelvic amputation.
      RESULT: Patients were followed up from 4 months to 14 years (average 51.7
      months). The limb function was preserved to some extent, and pelvic stability was
      satisfactory. Walking gait was not chlanged significant in group I and II. But
      resection without hip joint reconstruction in group III resulted in limb
      discrepancy (4.0 - 8.0 cm) and walking lamely. The patients needed custom-made
      shoes with heightened heel, but some of them walked with crutch when the
      discrepancy exceeded 8 cm. There were no nerve and vessel injury in the long run.
      The strength of muscles around hip joint was III - IV grade after postoperative
      exercise, and the capability of walking and viability recovered 3 months after
      the operation. CONCLUSION: Different surgical treatments should be selected
      according to the site of pelvic tumor. The classification system depending on the
      lesion's location in pelvic tumor is useful in selecting operative procedure to
      retain limb function to great extent.

PMID- 11825470
TI  - [Immunohistochemical investigations of congenital pseudarthrosis of the tibia].
AB  - OBJECTIVE: To investigate the etiology and pathology of congenital
      pseudarthrosis. METHOD: Sixty-three specimens were taken from 21 CPT patients.
      The antibodies, which were used for immunohistochemical studies, were produced
      against (1) NF-200 or S-100 protein; (2) type I or III collagen; (3) PCNA. The
      control specimens were taken from neurofibromatosis and traumatic pseudarthrosis.
      SABC staining was performed. RESULT: Low positive expression of NF-200 (3.2%) and
      S-100 (4.8%) was noted in the CPT lesion, whereas high expression of NF-200
      (85.2%) and S-100 (88.9%) in the lesion of neurofibromatosis. The soft tissues in
      CPT had a higher ratio of type III to I collagens in comparison with traumatic
      pseudarthrosis. Positive expression of PCNA (95.2%) was significantly higher in
      the soft tissues than that (2.5%) in traumatic pseudarthrosis. CONCLUSION: CPT is
      a disease of non-neuro origin. Its occurrence has no direct relation with
      neurofibromatosis. CPT has its characteristic pathology in the periosteum rather
      than in the bone. The pathological fracture or non-union of CPT is caused by
      fibromatosis, which has a strong activity of cellular proliferation and
      corrosion. CPT has its pathological property similar to a tumor.

PMID- 11825471
TI  - [Clinical study on traumatic anterior instability of shoulder].
AB  - OBJECTIVE: To study the clinical diagnosis, conservative and surgical treatment
      of traumatic anterior instability of the shoulder. METHOD: Based on the
      experience in diagnosis and treatment of 41 patients, we put forward criteria for
      diagnosis and treatment of traumatic anterior instability of the shoulder.
      RESULT: Diagnostic criteria: (1) history of injury to the shoulder; (2) sharp
      pain in the anterior aspect of the shoulder and weakness and limitation of range
      of motion of the shoulder; (3) the positive apprehension sign and or anterior
      drawer test; (4) a Hill-Sachs bony lesion on roentgenogram and abnormal double
      contrast CT. TREATMENT: (1) rehabilitation program for the patients having
      symptoms less than 3 months and without anterior capsular rupture; (2) capsular
      repair and imbrication procedure for the patients having symptoms more than 3
      months, or not satisfied to the rehabilitation treatment, or severe anterior
      capsular rupture on double contrast CT. The results of the treatment were
      satisfactory with average 16-month follow-up. CONCLUSION: The diagnostic criteria
      and the treatment principles help improve the results of treatment of shoulder
      injuries, further clinical study is needed for traumatic anterior instability of
      the shoulder.

PMID- 11825472
TI  - [Tissue engineering of hyaline cartilage].
AB  - OBJECTIVE: To study the new way to repair the defect of the articular cartilage.
      METHOD: The articular-epiphyseal cartilage complexes from 8 newborn rabbits were
      enzymatically dissolved, and the chondrocytes were seeded onto the fibrous chitin
      mesh in a 96-well plate in DMEM medium. RESULT: Cultured for 21 days, the
      "membrane-like cartilage" was strong enough to be transferred. At the 110th day,
      the semitransparent cartilage discs were 4.4 mm in diameter and 14.8 mg in
      weightness. Staining of SatranO showed that engineered "cartilage" was bound of
      GAGs and the chondrocytes expressed the mRNA of type II collagen by in situ
      hybridization, which is resemble to that of the normal hyaline cartilage beside
      the biodegraded fibrous chitin embedded in. The "membrane-like cartilage"
      cultured for 21 days was grafted into the articular cartilage defects of knee of
      adult rabbits. Seven of 9 defects healed with new cartilage and the structure was
      well organized in 16 weeks. CONCLUSION: The biodegradable fibrous chitin is a
      good "matrix" for cartilage tissue engineering. The engineered "cartilage" is
      true hyaline cartilage, which is a new "alive cartilage tissue" for the
      repairment of the defect of articular cartilage.

PMID- 11825473
TI  - [Bone scintigraphy in evaluating revascularization of the heat-devitalised
      autografts in adult dogs].
AB  - OBJECTIVE: To establish an animal model of microwave hyperthermic devitalization
      of long bones and compare bone scintigraphy of the devitalised bone with
      pathologic examination. METHOD: 16 Mongrel adult dogs were used. Enght 8 cm of
      one femur of each dog was exposed and isolated by heat-proof material. Two
      microwave antennas were inserted into the medullary cavity at a distance of 2.5
      cm, and the bone was heated intermittently to maintain a surface temperature of
      50 degrees C to 60 degrees C for 30 minutes. Bone scintigraphy was carried out at
      different postoperative time, combined with tetracycline labeling,
      microangiography with Indian ink and HE staining. RESULT: About 5 cm - 6 cm of
      segmental femur was deprived of blood supply after devitalization which was
      confirmed by microangiography and negative labeling of tetracyclines. At two
      weeks, the devitalised bone demonstrated a cold region on the scintiscan and no
      revascularization in microangiography. 12 - 16 weeks after the operation, partial
      devitalised bone was revascularized and HE staining showed widel bone resorption
      and minimum formation of new bone. However, the radionuclide uptakes of the
      devitalised segments were greater than those of the normal femurs. At one year,
      the devitalised segment was well (not completely) revascularised and showed
      evident appositional new bone formation. The scintigraphic bone-imaging was
      slightly lower than that of the normal femur. CONCLUSION: A strong positive
      scintiscan in early stage might demonstrate a good potential of revascularization
      of the heat-devitalised cortical bone rather than its viability. And the
      scintiscans of long-term follow-up more than one year should be more informative.

PMID- 11825474
TI  - [Thyroid cancer during pregnancy].
AB  - OBJECTIVE: To study the diagnosis and treatment of thyroid cancer during
      pregnancy. METHOD: 12 pregnant patients with thyroid cancer were retrospectively
      analysed. RESULT: Diagnosis was dependent on the clinical manifestation, the
      examination of B-ultrasonic and the fine-needle aspiration biopsy of thyroid, 4
      patients who asked for ending pregnancy were operated on after abortion, 6
      patients with early and middle pregnancy were operated on during pregnancy, and 2
      patients with late pregnancy were operated on after delivery. No patients showed
      recurrence of cancer, and their children were healthy, and the shape and function
      of the children's thyroid were normal. CONCLUSION: Pregnant patients with thyroid
      cancer during early and middle pregnancy should be operated on in time, and late
      pregnant patients should be operated on after delivery. All patients should take
      levothyroxine.

PMID- 11825475
TI  - [Microelectrode-guided posteroventral pallidotomy for Parkinson's disease:
      clinical study of 100 cases].
AB  - OBJECTIVE: To evaluate the outcome of posteroventral pallidotomy (PVP) for
      Parkinson's disease (PD). METHOD: The data from 100 patients with PD receiving
      PVP were retrospectively analyzed with UPDRS. RESULT: PVP significantly improved
      PD symptoms. Several typical symptoms were improved:tremor in 72% patients,
      rigidity 81%, akinesia 71%, gait 60%, balance 64% and off state 75%. CONCLUSION:
      PVP improves Parkinsonian symptoms, and is superior to classical thalamotomy.
      Microelectrode recording is essential to surgical results and avoidance of severe
      complication.

PMID- 11825476
TI  - [Bilateral ureter within single nipple for cutaneous ureterostomy after radical
      cystectomy].
AB  - OBJECTIVE: To evaluate the effect of bilateral ureter within single nipple for
      cutaneous ureterostomy after radical cystectomy. METHOD: Bilateral ureter within
      single nipple for cutaneous ureterostomy was performed on 36 patients after
      radical cystectomy. RESULT: The nipple was formed well, and urinary drainage was
      patent. No death or severe complication occurred. The patients have been followed
      up for 3 months to 3.5 years. Urinary, electrolyte and renal functions were
      within normal levels. No pyelonephritis or hydronephrosis was observed in IVP,
      retrograde pyelography and/or sonographic examination of kidneys, no nipple
      constriction. A right ureter was pulled to the left retroperitoneum and formed a
      nipple with ureter left on the left abdominal wall. CONCLUSION: This is a simple
      and safe operation, especially suitable to the old and weak patients.

PMID- 11825477
TI  - [The detection of circulating hepatocellular carcinoma cells in peripheral venous
      blood by reverse transcription-polymerase chain reaction and its clinical
      significance].
AB  - OBJECTIVE: To detect circulating hepatocellular carcinoma by demonstrating
      hepatocellular carcinoma cells-associated mRNA in the nuclear cell component of
      peripheral blood (PBL). METHOD: Peripheral blood (5 ml) samples were obtained
      from 93 patients with hepatocellular carcinoma (HCC) and from 37 controls (15
      controls with liver cirrhosis after hepatitis B, 12 chronic hepatitis B, and 10
      normal liver function). To identify HCC cells in peripheral blood, liver-specific
      human alpha-fetoprotein (AFP) mRNA was amplified from total RNA extracted from
      whole blood by reverse transcription-polymerase chain reaction. RESULT: AFP mRNA
      was detected in 50 blood samples from the patients with HCC (53.8%). In contrast,
      there were no clinical control patients whose samples showed detectable AFP mRNA
      in PBL. The presence of AFP mRNA in blood seemed to be correlated with the stage
      (by TNM classification) of HCC, the serum AFP value, and the presence of
      intrahepatic metastasis, portal vein thrombosis, tumor diameter and/or distant
      metastasis. AFP mRNA was detected in the blood of 21 patients showing metastasis
      at extrahepatic organs (100%) in contrast to 29 of 72 patients without metastasis
      (40.3%). CONCLUSION: The presence of AFP mRNA in peripheral blood may be an
      indicator of malignant hepatocytes, which might predict hematogenous spreading
      metastasis of tumor cells in patients with HCC.

PMID- 11825478
TI  - [The changes of electrogastrogram and gastrointestinal pressure following
      cholecystectomy].
AB  - OBJECTIVE: To investigate the mechanism and pathophysiological changes after
      abdominal surgery. METHOD: Twenty-two patients after cholecystectomy were
      selected to perform cutaneous electrogastrography (EGG) at least one hour before
      operation, and the first, the second and the third day after operation
      respectively. On the operative and postoperative days, gastroduodenojejunal
      manometry was performed in 17 of the 2 patients. RESULT: The percentage of EGG
      normal frequency on the operative day was obviously lower than that on the
      preoperative day (P < 0.001), and the percentage of bradygastria on the operative
      day was obviously higher than that on the preoperative day (P < 0.01). The
      postoperative EGG amplitude was obviously lower than the preoperative one (P <
      0.001), and did not recover after three days. The phase III of the migrating
      motor complex (MMC) appeared within 24 hours after operation, and first appeared
      at the duodenum. MMC III was most vigorous at the duodenum in recording period,
      and was less at the antrum. The contractile power and the area of MMC III at
      antrum after operation were obviously lower than at duodenum and upper jejunum (P
      < 0.01). On the third day after operation, the contractile power was lower than
      normal (P < 0.01). CONCLUSION: Gastrointestinal motility dysfunction after
      cholecystectomy is related to EGG amplitude, and not to EGG frequency. The
      recovery of antrum MMC III is later than that of small bowl, resulting in delayed
      gastric emptying. The MMC III of small bowl resums in early period after
      abdominal surgery. Postoperative ileum is due the decrease of MMC III contractile
      power and the area after abdominal surgery, which represent the ability of
      gastrointestinal contraction.

PMID- 11825479
TI  - [Cellular apoptosis, proliferation and bcl-2 Bax expression in colorectal
      carcinoma and their association with tumor prognosis].
AB  - OBJECTIVE: To investigate the relationship between cellular apoptosis,
      proliferation and bcl-2/bax expression in the tissue of colorectal carcinoma and
      biological behavior of the tumor. METHOD: The apoptotic cells index (AI) in situ
      were identified by the terminal deoxynucleotidyl transfer-mediated dUTP-biotin
      nick end labeling (TUNEL) and immunohistologic staining for Ki-67 proliferation
      index (KI), bcl-2/bax protein expression was performed on archival material from
      77 adenocarcinomas. RESULT: The mean AI and KI were 5.3/45.4 in early stage
      cancer, 5.6/48.7 in non-metastatic cancer, 6.6/55.3 in advanced cancer and
      8.9/60.1 in cancer with distant metastasis respectively. There was a positive
      relationship between the AI and KI in each specimen. bcl-2 and bax was expressed
      as 54.5%, 74% in carcinoma and highly differentiated carcinoma. In the univariate
      analysis, significantly longer survival time was observed in the subgroup of bcl
      2 positive carcinoma with low AI. In the multivariate analysis, tumor stage,
      tumor type, KI, and bcl-2 expression were independent risk factors for prognosis.
      CONCLUSION: The data indicate that abnormally exchanged AI/KI, bcl-2/bax
      expression appears to be an event associated with tumor progression and apoptosis
      might also reflect the proliferative activity of human colorectal carcinoma.

PMID- 11825480
TI  - [Preoperative staging of esophageal carcinoma: comparison of endoesophageal
      ultrasonography, computerized tomography and conventional clinical staging].
AB  - OBJECTIVE: To evaluate the value of different methods in preoperative staging of
      esophageal carcinoma. METHOD: Thirty-six patients undergoing resection of
      esophageal carcinoma were examined with endoesophageal ultrasonography (EU)
      before operation. Eight of 36 patients could not be evaluated because of severe
      esophageal stenosis. Computerized tomography (CT) was performed in 21 patients.
      Comparison was made between stagings based on EU, CT as well as the conventional
      clinical staging system, respectively with surgical-pathological staging after
      resection. RESULT: The accuracy of conventional clinical staging for esophageal
      cancer was only 36%. The accuracy of CT in T, N and pTNM staging was 38.1%, 57.1%
      and 47.6% respectively. For EU, the figures were 77.8%, 72.2% and 72.2%, and were
      improved to be 85.7%, 78.6% and 83.1% when untraversable patients were excluded.
      CONCLUSION: While conventional clinical staging system lacks accuracy in
      evaluating esophageal carcinoma, CT makes only moderate improvement. Based on
      direct morphological examination of lesions, EU is highly accurate in
      preoperative staging of esophageal carcinoma, especially in evaluating the extent
      of luminal wall invasion and regional lymph node involvement. Therefore, EU is of
      critical value in the therapeutic selection for esophageal carcinoma.

PMID- 11825481
TI  - [Clinical application of transesophageal intraluminal ultrasonography to the
      esophageal carcinoma].
AB  - OBJECTIVE: To study the value of transesophageal echo probe (TEEP) in
      preoperative staging of esophageal carcinoma. METHOD: Between September 1996 and
      August 1997, 32 patients (22 men and 10 women) with esophageal carcinoma, aged 49
      to 72 years (mean age, 55.2 years), underwent surgery. Preoperative examinations
      included upper gastrointestinal series, endoscopy, and TEEP. Seven of these
      patients also received CT scan. Resected specimens of the esophagus and lymph
      nodes were examined histopathologically, and the results of TEEP and CT were
      compared with intraoperative macroscopic findings and pathologic results. RESULT:
      The tumor length measured by gastroscopy, TEEP and pathology was 4.524 +/- 1.806
      cm, 5.269 +/- 1.916 cm, and 5.345 +/- 1.901 cm, respectively. There was a
      significant difference between the results of gastroscopy and those of pathology
      (P < 0.05), but no significant difference was seen between the results of TEEP
      and those of pathology (P > 0.05). The accuracy of TEEP for predicting T and N
      staging was 80.6% (25/31) and 77.3% (34/44), respectively. The accuracy of CT for
      predicting T staging was only 42.9%. CONCLUSION: TEEP is a reliable method for
      the preoperative TN-staging of esophageal carcinoma and it is more accurate than
      CT. TEEP is more accurate than gastroscopy in measuring the length of esophageal
      cancer. In our experience, the procedure is safe without any complications.

PMID- 11825482
TI  - [Bile salt induces apoptosis of hepatocytes: the mechanism of hepatic function
      injury during obstructive jaundice].
AB  - OBJECTIVE: To determine if the bile salt induces hepatocyte apoptosis in vitro.
      METHOD: Hepatocytes were isolated by in situ collagenase perfusion and plated in
      6 well flat bottom with DMEM/F12, 0.5 micro/ml insulin. Two hours later,
      glycochenodeoxcholate (GCDC) 25, 50, 100, 200, 300 micromol was added and cells
      evaluated by DNA-PI staining FACS and terminal-deoxynucleotidyl transferase
      mediated nick end labeling (TUNEL) 3, 6, 9, 12, 18, 20, 24 hours later. Agarose
      gel electrophoresis of DNA extracted from hepatocytes after incubation with GCDC
      using various experimental conditions. RESULT: The hepatocytes treated with GCDC
      have a high apoptotic rate as compared with the controls. 100 micromol GCDC
      treated 24 hours, nearly 61.81% of hepatocytes were apoptotic by FACS evaluation.
      The TUNEL showed that apoptotic hepatocytes had less cell volume and stained with
      brown by Biotin-11-dUTP. DNA ladder of bile-salt treated hepatocytes were shown
      in agarose gel electrophoresis. CONCLUSION: The mechanism of hepatic injury
      during obstructive jaundice is related to bile salt caused hepatocyte apoptosis.

PMID- 11825484
TI  - [Functional changes of forelegs of rats after C6 and C8 nerve roots resection:
      experimental study].
AB  - OBJECTIVE: To find new nerve roots as dynamic source, we observed the effect of
      C(6) and C(8) resection on the function of forelegs of roots. METHOD: Considering
      the relationship between C(6) and biceps brachii muscle, C(8) and flexor
      digitorum profundus muscle, we resected C(6) and C(8) nerve roots of right side
      as the experimental side and compared with the left side. The position, pace,
      appearance of ulcer were observed on the foot and the phenomena of self-injury
      were seen regularly. The EMG and tensile strength of biceps brachii and flexor
      digitorum profundus muscles were measured immediately at two weeks and four weeks
      after operation. RESULT: The position of two sides of the rats was symmetrical.
      There were no limp, ulceration and phenomena of self-injury. Normal wave figure
      in EMG was noted in the experimental side. There was no significant difference in
      t test in EMG wave amplitude, maximum tetanized systole tensile strength and
      duration of isometric contraction. CONCLUSION: C(6) and C(8) nerve roots
      resection has no obvious influence on function of the leg.

PMID- 11825483
TI  - [The osteoinductivity and the dose-effect relationship with implantation of
      reconstituted bone xenograft: experimental study].
AB  - OBJECTIVE: To observe osteoinductivity and the dose-effect relationship with
      administration of reconstituted bone xenograft (RBX). METHOD: A posterior thigh
      muscle pouch model with RBX transplantation was established in BALB/C mice.
      Samples were treated at regular postoperative intervals for radiologic,
      histomorphologic and ALP examinations. RESULT: (1) In the groups that had been
      implanted with RBX, the osteoinductivity was positively correlated with the bBMP
      contents in RBX (r = 0.7204, P < 0.01), showing a dose-dependent relationship;
      (2) satisfactory osteogenesis was noted in the RBX I group, whereas no
      substantial bone formation was seen in the group implanted with bBMP alone apart
      from some evidence of osteogenic effect; (3) the alkaline phosphatase activity
      attained its peak on the 7th day postoperatively and kept still higher to the
      42nd day. CONCLUSION: RBX is a highly osteoinductive grafting material with the
      treated homologous cancellous bone being a good slow-delivery carrier which can
      enhance the osteoinductive capacity of bBMP.

PMID- 11825485
TI  - [Effect of TNF-alpha monoclonal antibody on tissue lipopolysaccharide-binding
      protein mRNA expression in rats after thermal injury].
AB  - OBJECTIVE: To explore the effects of tumor necrosis factor-alpha (TNF-alpha)
      monoclonal antibody (MAb) on tissue TNF-alpha and lipopolysaccharide-binding
      protein (LBP) mRNA expression, and multiple organ dysfunction in rats after
      thermal injury. METHOD: 24 male Wistar rats were subjected to a 35% total body
      surface area full-thickness thermal injury. RESULT: The tissue TNF-alpha and LBP
      mRNA expressions of liver, lung, intestine, and kidney were markedly increased (P
      < 0.05 approximately equal 0.01) after thermal injury. Treatment with TNF-alpha
      MAb could significantly lower TNF-alpha mRNA expression of lung, intestine and
      kidney, but had no effect on liver TNF-alpha mRNA expression (P > 0.05).
      Similarly, the tissue LBP mRNA expression also decreased significantly (36.0% -
      72.9%), and returned to normal in lung, intestine and kidney. In addition,
      biochemical parameters including GPT, TBiL, BUN, CK-MB, and LDH were markedly
      elevated after thermal injury, and decreased significantly after treatment with
      TNF-alpha MAb. CONCLUSION: The increase of tissue TNF-alpha gene expression
      caused by thermal injury might be associated with a marked elevation of tissue
      LBP mRNA expression, which could contribute to the development of multiple organ
      dysfunction. The early use of TNF-alpha MAb seems to be effective in inhibiting
      significant LBP mRNA expression in various tissues and ameliorating multiple
      organ damage after major thermal injury.

PMID- 11825487
TI  - [Hepatic metastasis from advanced gallbladder carcinoma: clinicopathological
      study].
AB  - OBJECTIVE: To clarify the characteristics of the related clinicopathological
      factors in cases of liver metastasis from carcinoma of the gallbladder (LmGbCa),
      and to provide some insights into the surgical management of LmGbca. METHOD: One
      hundred fifty-nine patients with subserosal (ss) cancer were studied. RESULT: 31
      (19.4%) of the patients were found to have LmGbCa. Clinicopathologically, LmGbCa
      cases showed significant correlations with hinf(3) (P < 0.05), a depth of
      invasion of more than ss (P < 0.05), ly(3) (P < 0.05), v(3) (P < 0.01), and the
      location of the primary lesion on hep or circ (P < 0.01). CONCLUSION: Hepatectomy
      of S4 and S5 segments should be used when 2 risk factors of liver metastases were
      found operatively, and radiation therapy or chemotherapy should be combined with
      resection when 1 risk factor of liver metastasis and lymphatic invasion was
      found.

PMID- 11825486
TI  - [Effect of recombinant human growth hormone with total parenteral nutrition on
      albumin synthesis in patients with peritoneal sepsis].
AB  - OBJECTIVE: To investigate the effect of recombinant human growth hormone (rhGH)
      in combination with total parenteral nutrition (TPN) on albumin synthesis in
      patients with peritoneal sepsis. METHOD: 17 patients with peritoneal sepsis were
      divided randomly into two groups. The control group received TPN only for 7 days,
      and the GH group received both rhGH (12 U/d) and TPN for 7 days. The TPN scheme
      and other treatment were the same in the two groups. RESULT: Serum albumin,
      prealbumin, and transferrin concentration were increased in patients in the GH
      group (P < 0.01), but no apparent effect was observed in the control group (P >
      0.05). CONCLUSION: In condition of serious peritoneal sepsis, TPN can not
      increase albumin, prealbumin, and transferrin synthesis alone, whereas rhGH in
      combination with TPN significantly increase the synthesis of visceral proteins.

PMID- 11825488
TI  - [Cholelithiasis and cholecystectomy for colorectal cancer: a retrospective
      analysis].
AB  - OBJECTIVE: To study the relationship between cholelithiasis and previous
      cholecystectomy for colorectal cancer. METHOD: Retrospectively, the frequency of
      occurrence of gallstones and cholecystectomy for 238 patients with colorectal
      cancer diagnosed pathologically was compared with that of 395 matched controls
      for age and sex. The patients were checked by type B ultrasonography or had
      cholelithiasis and underwent cholecystectomy. RESULT: The relative risk (OR) of
      cholelithiasis and prior cholecystectomy associated with colorectal cancer was
      2.95 (95% confidence limits 1.89 - 4.59, chi(2) = 22.31, P < 0.01). The ratio of
      cholelithiasis to cholecystectomy was 40 vs 13 (P < 0.01) patients. Nine of the
      13 patients were over 60 years old (P < 0.01). The incidence of cholelithiasis
      associated with colon cancer was 36.2% (42/116), but it was only 9% (11/122) with
      rectal cancer (P < 0.01), and OR of cholelithiasis accompanied with colon cancer
      and rectal cancer was 1.37 and 1.99 respectively in female male. Cholelithiasis
      was more common in right-sided colonic cancer than in the left-sided in female
      (OR = 2.1) but there was no significant difference. CONCLUSION: Cholelithiasis
      other them cholecystectomy increases the risk of large bowel cancer, in addition,
      the relative risk of colorectal cancer is increased in patients of above 60 years
      old having previous cholecystectomy.

PMID- 11825489
TI  - [Hepatitis B virus replication status and its response to surgery for tumor in
      hepatocellular carcinoma patients with positive markers of HBV].
AB  - OBJECTIVE: To investigate the status of hepatitis B virus (HBV) activity in
      patients with hepatocellular carcinoma (HCC) and its response to surgical
      interventions for tumor in HBV positive HCC patients. METHOD: We analyzed HBV
      marker results and detected HBV DNA in sera of 97 HCC patients (pre-operation 66
      cases, post-operation 31 cases) with polymerase chain reaction (PCR) assay. We
      also investigated the HBV DNA titer in sera before and one week after operation
      in 20 HCC patients with positive HBV markers by quantitative polymerase chain
      reaction (Q-PCR). RESULT: HBV DNA positive rate in sera was 40.9% and 64.52% in
      the two subgroup respectively (P < 0.05). HBV DNA titer in sera increased after
      operation (P < 0.01). CONCLUSION: The infection rate of HBV in Chinese HCC
      patients is very high. The replication of hepatitis B virus is strong in partial
      HBV marker positive HCC patients and surgical interventions may promote the virus
      replication.

PMID- 11825490
TI  - [Comparison of nuclear accumulation of p53 protein with mutations in the p53 gene
      on the tissues of human breast cancer].
AB  - OBJECTIVE: To compare nuclear accumulation of p53 protein with mutations in the
      p53 gene on the tissues of human breast cancer. METHOD: Fifty-four invasive
      ductal carcinomas of breast were analyzed by polymerase chain reaction-single
      strand conformational polymorphism (PCR-SSCP) silver stain and strep-avidin
      biotin-peroxidase complex (SABC) immunohistochemistry. RESULT: A highly
      significant association between the presence of p53 gene mutation and nuclear
      accumulation of p53 protein was found (r = 0.714, P < 0.01). All 22 tumors with
      p53 gene mutations showed nuclear accumulation of p53 protein. Of the 32 tumors
      with gene mutations undetected, 9(28%) showed nuclear accumulation of p53
      protein. Both p53 mutation protein and p53 gene mutations were prevalent in
      steroid and progesterone receptors negative tumors (P < 0.05). There was a
      statistically significant association between the nuclear accumulation of p53
      protein and lymph node invasion (P < 0.05). So did p53 gene mutations (P < 0.05).
      Therefore, p53 abnormalities might be associated with an aggressive phenotype in
      breast cancer. CONCLUSION: The immunohistochemical detection of nuclear p53
      protein accumulation is highly associated with p53 gene mutations in breast
      cancer tissues. This method is useful for rapid screening of p53 abnormalities.
      In some cases of slightly positive for p53 nuclear protein we must observe p53
      genemutations to avoid the false positive reaction.

PMID- 11825491
TI  - [Maisonneuve fracture of the fibula: clinical and experimental study].
AB  - OBJECTIVE: To study the traumatic mechanism and clinical treatment of Maisonneuve
      fracture. METHOD: 19 of 25 patients (6 - 60 months, average 16.8 months) were
      followed up. 11 patients were operated on and 8 were treated conservatively. Of
      the 25 patients, 8 had MRI. Osteotomy and serial section of the interosseous
      membrane (IOM) on fresh cadaveric specimens were doc carried out to observe the
      diastasis on stress mortise view. RESULT: Functional rehabilitation of the ankle
      joint: in 11 operative cases, 8 showed good results and 3 fair. In 8 conservative
      cases, 3 showed good results, 2 fair and 2 poor. MRI: IOM was ruptured in a range
      3 - 8 cm proximal to the tibial plafond in the 8 cases. No IOM rupture was found
      at the high fibular fracture level. Fresh cadaveric experiment: fixation of the
      medial side alone can not control the syndesmotic diastasis on the artificial
      Maisonneuve fracture model made on cadaveric specimen. CONCLUSION: The injury
      level of the IOM during Maisonneuve fracture may not be consistent with the high
      fibular fracture. The limited external rotation of the fibula during injury by
      the superior tibio-fibular syndesmosis comprise to the high level fibular
      fracture. ORIF with syndesmotic fixation is recommended for the treatment.

PMID- 11825492
TI  - [Anatomical study and clinical observation of thoracic outlet syndrome].
AB  - OBJECTIVE: To investigate the etiology of thoracic outlet syndrome (TOS) from the
      point of anatomical and clinical view. METHOD: Anatomical study was made on both
      sides of 30 cadavers. The minimus scalene muscle and the insertions of anterior
      and middle scalene muscle were dissected and observed. Clinically, 45 cases of
      thoracic outlet syndrome (TOS) were treated and followed up. RESULT: The minimus
      scalene muscle was found in 88.3% of the cadavers. T(1) nerve root or the lower
      trunk of brachial plexus crossed the first rib just over the proximal tendinous
      part of minimus scalene muscle. Of 45 cases of TOS 34 presented neck-shoulder
      pain 17 had. Unchanged symptoms postoperatively, and 7 had aggravated symptoms.
      Of the recent 8 cases of TOS, 7 presented neck-shoulder-pain. However, the
      symptom remained in only case after the resection of the tendinous tissue around
      5, 6 nerve root from anterior and middle scalene muscle. CONCLUSION: The
      tendinous tissue of minimus muscle is the cause of the compression of T(1) nerve
      root or the lower trunk of the brachial plexus. The crossed tendinous origins
      from the anterior and posterior tubercle of C(4,5) transverse process is the
      cause of the compression of C(5,6) nerve root or the upper trunk of brachial
      plexus.

PMID- 11825493
TI  - [Parameters of arterial occlusion during intracranial aneurysm surgery].
AB  - OBJECTIVE: To evaluate parameters, owing to temporary and/or permanent
      intraoperative arterial occlusion, could be related to the postoperative
      development of ischemic injury. METHOD: During 3-year period between October 1994
      and March 1997, 27 patients with intracranial aneurysm were operated on with the
      aid of temporary and/or permanent arterial occlusion. Continuous intraoperative
      monitoring lCBF of the territories undergoing occlusion was carried out using
      LDF. Univariate analysis was used to study the relationship between the study
      variable and cerebral infarction. These variables included patient age,
      sexuality, aneurysm size, preoperative Hunt and Hess grades, LDF baseline value,
      LDF value following arterial occlusion and release of occlusion, the duration of
      arterial occlusion, the numbers of occlusive episodes, and the degree of arterial
      occlusion. Student's t-test was used for comparison of continuous variable such
      as age, and chi-square analysis was used to test the association of categorical
      variables. RESULT: The LDF value following arterial occlusion or residual lCBF,
      the duration of arterial occlusion, the numbers of occlusive episodes, and the
      occlusive degree were found to be significantly related to the postoperative
      development of ischemic injury. CONCLUSION: The residual lCBF and collateral
      circulation following arterial occlusion can be evaluated using LDF monitoring.
      When residual lCBF is more than 50 per cent of the baseline and the duration of
      arterial occlusion less than 20 minutes, temporary arterial occlusion is safe and
      does not develop postoperative ischemic injury.

PMID- 11825494
TI  - [The significance of changes in serum soluble lipopolysaccharide receptor CD14
      levels in burned patients with multiple organ dysfunction syndrome].
AB  - OBJECTIVE: To determine whether an increased soluble lipopolysaccharide receptor
      CD14 (sCD14) level is associated with the development of multiple organ
      dysfunction syndrome (MODS) in patients after major burns. METHOD: 22 patients
      with burns covering more than 70% of body surface area were studied. These
      patients were divided into two groups according to the occurrence of MODS (MODS
      group, n = 9; non-MODS group, n = 13). Blood samples were obtained from burned
      patients. Serum concentrations of sCD14 and tumor necrosis factor (TNF) were
      determined by sandwich ELISA. Plasma endotoxin was measured using a quantitative
      chromogenic LAL test. RESULT: Compared to the healthy volunteers, a significant
      increase in serum sCD14 levels was observed in 22 patients on day 7 postburn,
      which remained marked elevation up to 21 days after thermal insult (P < 0.01).
      The serum sCD14 levels of the MODS group were significantly higher than those of
      the non-MODS group on days 7, 14, and 21 postburn (P < 0.05). Additionally, the
      serum sCD14 and endotoxin levels were positively correlated in patients who
      developed MODs on days 7, 14 and 21 postburn (P < 0.05), whereas no correlation
      was found between sCD14 and TNF levels at any time point (P > 0.05). CONCLUSION:
      Our data suggest that sCD14 elevation is associated with the development of MODS
      after major burns, and endotoxin release may be involved in the activation of
      sCD14 under certain pathophysiological conditions.

PMID- 11825495
TI  - [Treatment and prognosis of 33 patients with recurrent retroperitoneal soft
      tissue sarcomas].
AB  - OBJECTIVE: To investigate the treatment and the prognosis of patients with
      recurrent retroperitoneal soft tissue sarcomas. METHOD: The clinical data of 33
      patients, treated for recurrent retroperitoneal soft tissue sarcomas from 1972 to
      1996 were analyzed retrospectively. RESULT: Complete tumor resection was
      performed for 17 patients (51.5%) with tumor recurrence for the first time. 2, 3,
      1 patients underwent multiple organs resection respectively when the sarcoma
      relapsed initially, secondly and thirdly. Fourteen patients were given adjuvant
      radiotherapy and chemotherapy postoperatively. Twenty-nine patients were followed
      for up for 6 to 12 months. Fifteen (51.7%) of them died. Seven of them survived
      beyond 5 years and 2 over 10 years. The 1-, 3-, and 5-years survival rate was
      85.7%, 54.9% and 42.3% respectively. CONCLUSION: Surgery is effective in
      improving the survival rate of patients with recurrent retroperitoneal soft
      tissue sarcomas, including those with repeatedly recurrent sarcomas. Multiple
      organ resection could be beneficial to the curative resection rate. Adjuvant
      radiotherapy and chemotherapy might improve the local control of relapsed
      sarcomas to some extent.

PMID- 11825496
TI  - [Long-term outcome of selective posterior rhizotomy for spastic cerebral palsy].
AB  - OBJECTIVE: To investigate the long term outcome and complication of selective
      posterior rhizotomy for spastic cerebral palsy. METHOD: 26 patients with cerebral
      palsy who had received SPR were followed up for four years. RESULT: In the 9
      patients who could walk and stand up from squatting position independently, 7
      could stand steadily on one foot after operation. In the 12 who patients could
      walk and stand up from squatting position dependently, 7 could walk independently
      in the room after operation. In 5 patients couldn't walk and stand up from
      squatting position, 3 patients could walk dependently in the room after
      operation. Complications occurred in 3 patients. CONCLUSION: Selective posterior
      rhizotomy is effective in the treatment of spastic cerebral palsy. Strictly
      selecting candidates for the operation and good rehabilitation training before
      and after operation should be emphasized for good results.

PMID- 11825497
TI  - [Malakoplakia of the prostate].
AB  - OBJECTIVE: To study the diagnosis and treatment of prostatic malakoplakia.
      METHOD: Two cases of malakoplakia were reported, and the cases and articles were
      reviewed. RESULT: The disease is an inflammation of the prostate, and lower
      immunocompetence is concomitance. The patients had symptoms of dysuria and
      urethralgia. The tubercle could be found. Pathological section revealed
      malakoplakia cells and Michaelis-Gutman inclusion bodies. Many patients were
      performed radical prostatectomy because of misdiagnosis. CONCLUSION: Biopsy of
      the prostate and antibiotics should be used clinically.

PMID- 11825499
TI  - [Correction of mitral insufficiency with posterior annuloplasty].
AB  - OBJECTIVE: To summarize the experience in treating mitral insufficiency (MI), due
      to secondary annular dilation in the posterior portion of the annulus with mitral
      valve reconstruction. METHOD: Over the past 10 years, we performed mitral
      valvuloplasty with posterior annuloplasty in 35 patients, of which 27 patients
      were associated with congenital abnormalities, 3 patients had mild MI, 24 had
      moderate MI, and 8 had severe MI. Entire posterior annular plication was
      performed in 7 patients and partial posterior annular plication in 28. Associated
      subvalvulopasty was performed in 7 patients and leaflets repair reconstruction in
      14. RESULT: There was no postoperative mortality. Complete correction was
      achieved in 21 patients (60.0%) and partial correction in 11 (31.4%). Mild and
      moderate insufficiency was found in 3 patients (8.6%) postoperatively. NYHA
      function class I was gained in 34 patients. One patient developed pulmonary
      hypertension and died due to right heart failure five years after operation.
      CONCLUSION: The results indicate that posterior annuloplasty is a safe, effective
      technique.

PMID- 11825498
TI  - [Nontypical limited resection of the lung].
AB  - OBJECTIVE: To evaluate the role of limited resection in the treatment of lung
      disease. METHOD: From 1989 to 1996, 46 limited resections were performed on 35
      patients with lung diseases. All patients were followed up for 0.5 to 7 years
      (mean 29.3 months). RESULT: There were no operative deaths and operative
      complications. In 16 patients with benign lung diseases, no recurrences and late
      complications were found. In 5 patients with primary lung cancers, 2 died 1.5 and
      2 years after operation, respectively, and 3 are still living well for 2.5, 4 and
      5 years postoperatively. In 14 patients with metastatic lung diseases (10 with
      bilateral multiple metastases), 216 metastatic lesions were excised. 1-, 3-, and
      5-year survival rates were 78.5%, 50% and 21.4% respectively. CONCLUSION: Limited
      lung resection could be an additional option and a surgical alternative to
      conventional lung resection for some compromised patients.

PMID- 11825500
TI  - [Surgical treatment of cervical 1, 2 neurinomas].
AB  - OBJECTIVE: To analyse retrospectively 15 cases of C(1) and C(2) neurinomas
      treated between 1986 - 1997. METHOD: All patients were examined by clinical
      neurology, neuroradiology (CT/MRI/DSA) and identified operatively and
      pathologically. All samples were studied histopathologically. RESULT: Except 1
      patient died from menotic nerve sheath tumor involving medulla oblongata and pia
      mater, 14 patients were cured. CONCLUSION: Lateral approach may be idoal in total
      tumor resection and improvement of neurological symptoms.

PMID- 11825501
TI  - [Changes of PAI-1 and biological behaviour of human hepatocellular carcinoma in
      metastatic model of nude mice].
AB  - OBJECTIVE: To study the relationship between plasminogen activator inhibitor type
      1 (PAI-1) and biological behaviour of hepatocellular carcinoma (HCC). METHOD: 40
      nude mice with LCI-D20 metastatic modes of human HCC (MMHCC) were established.
      The change of PAI-1 was determined by PAI-1 kit and immunohistochemistry with
      monoclonal antibody against PAI-1 in MMHCC progression. RESULT: Following MMHCC
      progression from early to advanced stage, PAI-1 increased from 6.2 +/- 1.8 Au/ml
      to 15.4 +/- 0.7 Au/ml in plasma (P < 0.05), from 0.4 +/- 0.1 Au/mg to 0.8 +/- 0.3
      Au/mg in extract (P < 0.05). The correlation between PAI-1 and tumor size and AFP
      level was strong (r = 0.9648 and r = 0.9544, P < 0.05 and P < 0.05). CONCLUSION:
      PAI-1 was increased gradually following tumor progression in MMHCC. PAI-1
      correlated with tumor size and AFP level. PAI-1 related well with the
      invasiveness and prognosis of HCC.

PMID- 11825502
TI  - [Effect of CD11b/CD18 on burn-activated PMN-mediated permeability of pulmonary
      microvascular in isolated perfused lung].
AB  - OBJECTIVE: To determine the effect of intercellular adhesion molecule (ICAM-1)
      CD11b/CD18 in burn-activated PMN-mediated permeability of microvascular in
      isolated perfused lung. METHOD: Isolated lungs were distributed into 7 groups
      according to the different contents of perfused fluid: normal perfused fluid,
      normal rat serum, burn rat serum, normal rat PMN, burn rat PMN, normal rat PMN
      blocked by monoclonal antibody to adhesion molecule CD11b/CD18 and burn rat PMN
      blocked by antibody. The extent of isolated lung edema, vascular permeability to
      small molecules (fluid) and vascular permeability to large molecules (albumin)
      were expressed by lung weight gain (LWG), fluid filtration coefficient (Kf) and
      pulmonary albumin permeability-surface area product (PS) respectively. RESULT:
      Burn serum could increase LWG, Kf PS, so did burn-activated PMN. The latter could
      make PS increase more obviously. Monoclonal antibody to CD11b/CD18 on PMN could
      obviously decrease PMN sequestration in isolated perfused lung. The protective
      effect of antibody on increasing LWG and Kf, and particularly PS was
      demonstrated. CONCLUSION: (1) The effect of mediators from burn-activated PMN to
      EC was mediated by PMN adhesion to EC. (2) Some mediators from burn-activated PMN
      increase mainly the pulmonary vascular permeability to small molecules, and PMN
      adhesion to EC mediated by CD11b/CD18 may increase directly the permeability to
      large molecules. (3) Adhesion molecule CD11b/CD18 perhaps have an ability to
      regulate directly EC by combining its receptor ICAM-1 on EC.

PMID- 11825503
TI  - [Effect of various methods of tissue storage on split-skin viability at 4 degrees
      C].
AB  - OBJECTIVE: To study various tissues and organs storage solutions (liver, kidney
      and corneal) at 4 degrees C for the storage of skin and the viability of skins
      stored in these solutions at correspondent condition. METHOD: Five experiment
      groups investigated for storing porcine split-skin at 4 degrees C were MEM, UW,
      MEM plus CS, UW-R and MEM-R. A new assay, WST-1, was applied to evaluate skin
      viability at 1, 3, 5, 7, 10 and 14 day during storage respectively. RESULT: Skin
      viability can all be protected by these three solutions. The effect of UW
      solution was superior to MEM. UW-R and MEM-R were superior to MEM and UW.
      CONCLUSION: The method of UW-R which replaces medium routinely may be an optimal
      method of storing skin at 4 degrees C.

PMID- 11825504
TI  - [The effects of different instrumentation on scoliosis].
AB  - OBJECTIVE: To investigate the effectiveness of the treatment of scoliosis with
      different surgical methods. METHOD: 125 cases of scoliosis less than 100 degrees
      treated during 14 years (1984 - 1997) were analyzed. Different operative methods
      were compared for their advantages and disadvantages, i.e. results and
      complications 10 months after operation and follow-up. RESULT: Harrington
      instrumentation was less effective in scoliotic curve correction and had more
      complications than other procedures. Luque technique needed longer operation time
      for wire passage at each level and had risk of neurological damage. CD and Zielke
      method showed 10% - 20% curve correction. No dislodgment of hook and fractured
      rods was found in the CD group. Anterior release plus posterior instrumentation
      was superior to other techniques. CONCLUSION: Treatment of scoliosis with
      anterior release plus posterior CD is practical for children before a new
      technique without spinal fusion is developed.

PMID- 11825505
TI  - [Diagnosis and treatment of tethered cord syndrome in adults].
AB  - OBJECTIVE: To study the clinical characteristics of tethered cord syndrome (TCS)
      in adults. METHOD: 18 patients with TCS were confirmed by preoperative MRI and
      were operated on for releasing of tethered conus. Pathological mechanism and main
      points of operation were analysed according to the operative findings and
      radiological data. RESULT: The cord or conus were tethered by intradural tumors
      (6 patients), myelomeningocele (6), thickened filum terminale (3),
      diastematomyelia (2) and adhesion after operation (1). 14 of the 18 patients
      showed good results after follow-up for 8 months to 5 years. CONCLUSION: Clinical
      manifestation and prognosis of TCS in adults are different from those of TCS in
      children. Attention should be paid to avoid additional injury to the conus and
      cauda equina during operation. The long course of disease and retethering of the
      conus lead to poor outcome.

PMID- 11825506
TI  - [Clinical application of TMS-MEP in spinal cord injury].
AB  - OBJECTIVE: To evaluate transcranial magnetic stimulation motor evoked potential
      (TMS-MEP) in the diagnosis of spinal cord injury. METHOD: 56 patients with injury
      of the spinal cord and cauda equina were examined using TMS-MEP and followed up.
      RESULT: In 21 patients with complete paralysis, TMS-MEP of bilateral tibialis
      anterior and gastrocnemius disappeared and paralysis did not recover. Abnormal
      was noted TMS-MEP and paralysis not recovered in 2 patients with injury of conus
      medullaris and cauda equina. Incomplete paralysis occurred in 35 patients. TMS
      MEPs of more than one muscle in every patient were recorded. Paralysis and TMS
      MEPs recovered in different degree in the 33 patients, in which the strength was
      0 class and TMS-MEPs were abnormal in 25 target muscles before operation whereas
      their strength obviously recovered or even normalized after operation except two
      muscles. CONCLUSION: TMS-MEP is an effective method for diagnosis and prognosis
      of spinal cord injury.

PMID- 11825507
TI  - [Clinical significance of early diagnosis of cervical spondylotic myelopathy].
AB  - OBJECTIVE: To probe into the possibility of early diagnosis of cervical
      spondylotic myelopathy (CSM) prospectively and to screen the premorbid signs of
      CSM clinically, radiologically and electro-physiologically. METHOD: Twenty-nine
      items related to the occurring of CSM were chosen as common characteristics of
      CSM and considered as the criteria of prospective study. 81 patients who met the
      criteria were studied. All patients were followed up and observed for 2 - 6.5
      years (mean 3.7 years). RESULT: Twenty-nine patients showed CSM during
      investigation. Thirteen items of the criteria were related to the occurring of
      CSM. The significant items include upper limb pain and abnormal sensation limb
      numbness, positive dynamic Hoffmann's sign, cervical canal stenosis, lower
      cervical instability, cervical intervertebral disc herniation, and delay of
      central motor conduct time. CONCLUSION: CSM can be early diagnosed. The patients
      who meet the established criteria should be followed up and observed closely.
      Early operation results in good effect.

PMID- 11825509
TI  - [Bacterial distribution and antimicrobial resistance monitoring of surgical
      infection].
AB  - OBJECTIVE: To study the antimicrobial resistance of surgical isolates in Wuhan
      area. METHOD: The diameters of the inhibition zones of surgical isolates around
      antibiotic susceptibility test discs at 13 hospitals in Wuhan were computerfiled
      and analysed by the software of "WHONET-3" according to NCCLS published in 1993.
      RESULT: A total of 957 surgical isolates were collected in 1996. S. aureus, P.
      aeruginosa, E. coli and CNS were the main microorganisms. 12.4% of S. aureus was
      resistant to oxacillin and to other antimicrobials as well. Most strains of
      Enterobacteriaceae were resistant to ampicillin, with a resistant rate of more
      than 75%, but 93% for klebsiella sp. Imipenem, ceftazidime, amikacin and
      ciprofloxacin were most active agents against Gram (-) bacilli including
      Enterobacteriaceae and glucose nonfermenters. CONCLUSION: Antimicrobial
      resistance should be seriously considered during surgical therapy and prophylaxis
      with antimicrobial agents. The tendency to antimicrobial resistance of clinical
      isolates should be followed up continuously.

PMID- 11825508
TI  - [Effect of calmodulin inhibitor on spinal cord injury].
AB  - OBJECTIVE: To evaluate the effect of a special calmodulin (CaM) inhibitor
      trifluoperizine (TFP) on spinal cord injury (SCI) and the role of CaM in SCI.
      METHOD: We observed the effect of TFP on spinal cord blood flow (SCBF), motor
      evoked potentials (MEP) and motor function in SCI by using hydrogen clearance,
      inclined plane and electro physiological technique. RESULT: There was significant
      improvement of SCBF, MEP and motor function with TFP, when adrenaline maintained
      the system arterial pressure in SCI. CONCLUSION: Prevention by TFP of spinal cord
      function in SCI suggested that CaM plays a role in the pathogenesis of SCI.

PMID- 11825510
TI  - [A study of the gene encoding Ki-67 antigen in human pancreatic cancer using non
      radioactive in situ hybridization and immunohistochemistry].
AB  - OBJECTIVE: To investigate, at transcriptional and translational level in situ,
      the abnormal gene expression of the Ki-67 protein in pancreatic carcinoma
      specimens. METHOD: 40 pancreatic cancer specimens, 5 normal pancreatic and 4
      chronic pancreatitis tissues were studied. A 435 bp cDNA fragment located in
      codon 2, exon 13 of the Ki-67 antigen gene was amplified by the polymerase chain
      reaction (PCR). The DIG-labeled cRNA probes were transcribed using a commercially
      available DIG RNA labeling kit. Localization of the Ki-67 protein and the
      specific mRNA were studied by combining immunohistochemistry (ICH) with (DIG)
      labeled in situ hybridization (ISH). RESULT: The Ki-67 protein mRNA in formalin
      fixed and paraffin-embedded pancreatic tissue sections was successfully
      localized. Analyzing the Ki-67 mRNA transcription in 17 pancreatic cancer
      specimens with Ki-67 ICH labeling index > 20%, we found that stronger mRNA
      signals were also observed in poorly differentiated specimens with Ki-67 index >
      50% than in those well differentiated with ICH labeling index 20% - 50%. A high
      expression of both mRNA and protein was observed in poorly differentiated
      pancreatic adenocarcinomas. CONCLUSION: Abnormal overexpression of the gene
      encoding Ki-67 protein was detected not only at the protein level, but also at
      the mRNA level in pancreatic tumors. The abnormal overexpression of the Ki-67
      protein might be correlated with the central part, exon 13, of the gene.

PMID- 11825511
TI  - [The changes of pancreatic function after cardiopulmonary bypass].
AB  - OBJECTIVE: To evaluate the changes of endocrine and exocrine pancreatic function
      in patients who underwent heart valve replacement under cardiopulmonary bypass
      (CPB) in order to optimally conside clinical management perioperatively. METHOD:
      Sixteen patients with heart valve disease were selected. Serum glucose, lactate,
      insulin, C peptide, amylase and lipase were measured. RESULT: Hyperglycemia and
      hyperlactacemia were noted after CPB and peaked at 19:00 on the operative day.
      Their changes were correctly correlated. Serum glucose and lactate returned to
      the baseline level on the third postoperative day. The average level of serum
      insulin were normal, but higher on the third postoperative day. However, the
      level of serum C peptide was higher than the baseline. It doubled the baseline
      level at 19:00 on the operative day. The average level of serum amylase and
      lipase was normal, except the higher level of serum lipase on the fourth
      postoperative day. In our group, 12 patients had normal serum amylase level
      perioperatively, and 4 increased serum amylase level (25%), among them 2 patients
      accompanied with hyperlipasimia (16%). There were 8 patients with hyperlipasimia
      (50%). CONCLUSION: The endocrine and exocrine pancreatic functions were
      influenced by CPB and did produce pathophysiologic changes.

PMID- 11825512
TI  - [Expression of cell adhesion molecule CD44 variant isoform correlated with the
      clinical behavior of renal cell carcinoma].
AB  - OBJECTIVE: To determinate whether the expression of CD44v in renal cell carcinoma
      (RCC) is associated with tumor malignant behavior. METHOD: Reverse transcription
      polymerase chain reaction (RT-PCR) was used to detect CD44v in 31 human renal
      cell carcinoma (RCC) in addition to 18 normal renal tissues from patients with
      non-malignant disease. RESULT: Eighteen RCCs showed positive expression while
      none of normal renal tissue expressed CD44v (P < 0.001). CD44v was expressed in
      metastatic or high pathological stage RCC, but the expression of CD44v was not
      correlated with cellular differentiation. CONCLUSION: Our data indicate that a
      role for CD44v in human RCC progression and metastases, and CD44v may prove to be
      a marker for high metastasis potential of RCC.

PMID- 11825513
TI  - [The diagnosis and treatment of primary carcinoma of the duodenum].
AB  - OBJECTIVE: To improve the diagnosis and treatment of primary duodenal carcinoma.
      METHOD: The records of 18 patients with primary carcinoma of the duodenum were
      reviewed. RESULT: 7 cases underwent pancreatoduodenectomy: segmental duodenectomy
      (1), intraoperative death (1), survived 3 years (2), and survived 5 years after
      operation (3). 7 cases underwent gastroenterostomy or cholangioenterostomy; they
      died in 11 months after operation. Three cases who received biopsy only died in
      six months after operation. CONCLUSION: The understanding of duodenal carcinoma
      is the key factor for early diagnosis. The appropriate examinations are necessary
      for suspected patients. Once the diagnosis is confirmed, the result of surgical
      treatment is improved.

PMID- 11825514
TI  - [The indication and mode of surgery for the treatment of patients with severe
      acute pancreatitis].
AB  - OBJECTIVE: To study the indication and mode of surgical management in patients
      with severe acute pancreatitis (SAP). METHOD: 41 patients with SAP were grouped
      for conservative treatment or surgical. The main procedures of surgical
      management were pancreatic debridement, peripancreatic and coeliac drainage,
      combined with peripancreatic instillation and suction alternatively. RESULT:
      Conservative treatment was adopted in 22 patients (16 patients in grade I, 6 in
      grade II), among them 19 recovered, and 3 of grade II died. 19 patients underwent
      surgical treatment including 7 in grade I, 12 in grade II). 15 patients were
      cured, 4 patients of grade II died. CONCLUSION: Timely operation is necessary for
      the patients with infection and complications. Surgical intervention is
      recommended for patients older than 60 years old. Surgery should be less
      traumatic, simple and prompt. Surgical or conservative treatment are chosen
      according to the patients' conditions. The cure rate of SAP can be improved.

PMID- 11825515
TI  - [The surgical treatment of tetralogy of fallot in 136 adults].
AB  - OBJECTIVE: To summarize the experience of surgical treatment of tetralogy of
      Fallot (TOF) in adults. METHOD: From April 1975 to December 1997, 136 adult
      patients underwent total corrective repair of tetralogy of Fallot. The patient
      age ranged from 14 to 52 years old. The ventricular septal defects were closed
      with Dacron patch in 112 patients, with pericardial patch in 24 patients. A right
      ventricular outflow patch was required to eliminate right ventricular outflow
      tract obstruction in 126 patients. RESULT: Five patients died during
      hospitalization, with a hospital mortality of 3.68%. Four early postoperative
      deaths were due to severe low cardiac output syndrome. CONCLUSION: In view of
      current improved and standardized techniques, we conclude that the total
      corrective repair of TOF may have an excellent result in adult patients.

PMID- 11825516
TI  - [Surgical treatment of spinal dural arteriovenous fistulas].
AB  - OBJECTIVE: To discuss the operation modalities of spinal dural arteriovenous
      fistulae (SDAVFs) and treatment with anticoagulant agents after surgery. METHOD:
      The medical records, radiographic studies and operations of 23 patients with
      SDAVFs were reviewed. Laminectomy was performed at the level of the arterialized
      venous entry into the subarachnoid space in 18 patients with thoracic and lumbar
      lever AVFs, followed by coagulation, clipping and division of the vein. In 14 of
      18 patients, the arteriovenous nidus in the dura was identified and obliterated
      by coagulation. The draining veins were interrupted at L(5) - S(1) level in 5
      patients with sacral AVFs. Anticoagulant treatment was given in 13 patients.
      RESULT: Outcome was good in 20 patients and 2 of the 20 had transient
      postoperative neurological deterioration that reversed by anticoagulant agents.
      No changes were seen in 2 patients except one deteriorated. CONCLUSION: Surgical
      interruption of arterialized radicular-medullary draining vein of SDAVFs provides
      lasting occlusion of the fistula, and postoperative anticoagulant therapy can
      prevent thrombosis of the coronal venous plexus.

PMID- 11825517
TI  - [The methods of surgical removal of glioblastoma multiform under functional
      cerebral cortex].
AB  - OBJECTIVE: To find the superlative way of surgical removal of glioblastoma
      multiform under functional cortex by comparative study of 123 patients. METHOD:
      Surgical approaches include direct and total resection of tumors, trans
      functional cortex or adjacent area beyond functional cortex. They were compared
      with partial tumor resection plus external/internal decompressive procedure,
      total removal of tumor plus functional cortex resection. Comprehensive analysis
      was made. RESULT: Total removal of tumors both trans-functional or adjacent
      cortex prolonged the survival time of patients. As a result, minimal damage was
      observed in patients with both approaches, which are helpful for recovery of
      impaired cerebral function. On the other hand, partial resection of tumors in
      spite of combining with decompressive procedure or functional cortex resection
      did not show the same benefit. CONCLUSION: Surgical resection of glioblastoma
      multiform through trans-functional cortex or adjacent cortex beyond functional
      area is superior to other approaches both in dealing with total tumors removal
      and cerebral function recovery. But the resection through adjacent cortex beyond
      functional area in recovery of impaired cerebral function is more effective.

PMID- 11825518
TI  - [Analysis of clinicopathologic changes of infection in dead patients after renal
      transplantation].
AB  - OBJECTIVE: To prevent renal transplantation patients from infection. METHOD:
      Autopsies of 24 patients who had died after renal transplantation were studied.
      RESULT: The incidence of infection was 66.7% and the lethal infective
      complications amounted for 50%. The most infectious agents were bacteria, fungi,
      tuberculosis, virus and actinomyces. CONCLUSION: Pathological features and
      clinical manifestations of lesions were caused by aforementioned agents. Some
      management can prevent renal transplantation recipients from infection.

PMID- 11825519
TI  - [Dietary fiber protects intestinal structure and barrier function].
AB  - OBJECTIVE: To evaluate the effect of dietary fiber on intestinal structure and
      barrier function of 5-fluorouracil (5-Fu) challenged rat. METHOD: Thirty Wistar
      rats were divided randomly into three groups (10 each group): Chow, enteric
      nutrition (EN), and EN + Fiber group. Both EN and EN + Fiber group were
      isonitrogenic and isocaloric. The rats kept their diet respectively for 8 days. 5
      Fu was injected intraperitoneally on day 4 postoperatively. Intestinal
      permeability (L/M) was measured respectively on day 3 and day 7. On day 8, the
      bacterial translation, wet weight and mucous thickness of both small intestine
      and colon and the villus height of small intestine were measured. The rats were
      weighted before and after experiment respectively. RESULT: The body weight loss
      of the EN + Fiber group (-3.1 +/- 3.4 g) was less than that of the EN group (-6.6
      +/- 5.2 g) (P < 0.05), whereas the Chow group gained body weight (4.9 +/- 4.3 g)
      (P < 0.01 when compared with EN and EN + Fiber group). The parameters of
      intestinal structures of the EN + Fiber group was superior to the EN group (P <
      0.05). The L/M of both EN + Fiber (from 0.0265 +/- 0.0073 to 0.0274 +/- 0.0068)
      and the Chow group (from 0.0268 +/- 0.0039 to 0.0281 +/- 0.0044) was unchanged (P
      > 0.05 for both) after 5-Fu challenged, whereas that of the EN group increased
      (from 0.0289 +/- 0.0070 to 0.0331 +/- 0.0084) (P < 0.01). The incidence of
      bacterial translocation to MLN of both EN + Fiber group and the Chow group (20%)
      was lower than that of the EN group (70%) (P < 0.05). CONCLUSION: The dietary
      fiber protects the intestinal structure and barrier function of 5-Fu challenged
      rats.

PMID- 11825520
TI  - [Morphometrical study on inhibitory effect of vitamin B6 and banana-stem extract
      on calcium crystallization].
AB  - OBJECTIVE: To search for the anticrystallization mechanism by vitamin B(6) and
      banana stem extract. METHOD: Thirty-six male China-1 mice were divided into 4
      groups: normal, crystallization, vitamin B(6) and banana-stem extract groups.
      Calcium oxalate crystallization was induced by 1% glycol and 1% ammonium chloride
      in the last 3 groups. Vitamin B(6) was then given to the 3rd group and banana
      stem extract to the 4th group for 3 weeks. At the end of 3 weeks, all the mice
      were sacrificed and the kidneys were taken for morphometrical studies using image
      analysis system and assayed for calcium oxalate. RESULT: Morphometrical area
      density and numerical density of crystallization was significantly less in the
      vitamin B(6) group and the banana-stem extract group as compared with the
      crystallization group, being the least in the banana-stem extract group. Oxalate
      in renal tissue was also significantly reduced. Both vitamin B(6) and banana stem
      extract had no effect on renal tissue calcium. CONCLUSION: Vitamin B(6) and
      banana-stem extract may be useful agents in the treatment of patients with
      hyperocaluric urolithiasis.

PMID- 11825521
TI  - [Prevalence of childhood cerebral palsy in six provinces in China].
AB  - OBJECTIVE: To investigate the prevalence of childhood cerebral palsy (CP) in
      China. METHODS: A cross sectional survey was carried out among 1047327 children
      aged 1 approximately 6 years old in six provinces of China during May 1997
      approximately December 1998. RESULTS: The crude prevalence of CP for children
      aged 1 approximately 6 years old was 1.92 per thousand; in addition, prevalences
      of CP were also reported for factors such as sex, age, ethic group, birth weight,
      gestational age, and area. CONCLUSION: Prevalence of CP in China is at the low
      range among the world, which may be due to low prevalence and low survival rate
      of premature newborn in China. The prevalence of cp is associated with areas,
      sex, age, ethnic group, birth weight, and gestational age.

PMID- 11825522
TI  - [A further study on potential of microsatellite analysis of urine in diagnosis of
      bladder cancer].
AB  - OBJECTIVES: To investigate the application value of microsatellite analysis of
      voided urine in diagnosis of bladder cancer and compare the advantages and
      disadvantages of this method and urine cytology. METHODS: Thirteen microsatellite
      markers, including the nine markers used in the authors' previous study and
      another four new markers, were tested on urine DNA from 143 individuals with or
      without bladder lesions in a blinded fashion. Urine cytology was applied at the
      same time. RESULTS: The urine DNA from 89% (97/109) of the patients with bladder
      cancer, 86% (6/7) of the patients with inverted papilloma of the bladder, 3 out
      of 7 patients with cystitis and one patient with hematuria of unknown cause
      showed alterations, at least, in one of the 13 microsatellite markers, while the
      19 individuals without bladder lesion had no change at any of these loci. Nucleic
      atypia or suspicious cancer cells were detected by routine cytology in the urine
      of the 3 patients with cystitis and one patient with hematuria of unknown cause
      who showed alterations of microsatellite in their urine sediments. Among the 81
      cases of bladder cancer whose urine was examined by both microsatellite analysis
      and routine cytology, 73 cases (90%), of various stage or grade, were identified
      by microsatellite analysis, while only 41 cases (51%), mainly at advanced stage,
      were detected by cytology. Cancer cells were detected in the urine sediments of 4
      of the 12 cases that were not identified by microsatellite analysis. CONCLUSION:
      Microsatellite analysis of urine is useful for detection of bladder cancer.
      Microsatellite analysis and urine cytology could be complementary to each other.

PMID- 11825523
TI  - [Study on different responses of rats' small intestine mucous membrane and
      bladder transitional epithelium in the same carcinogenic urine environment].
AB  - OBJECTIVE: To preliminarily verify the tentative idea of replacement of bladder
      transitional epithelium with small intestine mucous membrane to prevent
      recurrence of carcinoma of bladder. METHODS: A certain segment of small intestine
      was transplanted to the urinary bladder of the same body in 17 rats. Then N-butyl
      N-(4-hydroxy-butyl) nitrosamine (BBN) was used to induce carcinoma of bladder.
      BBN was used to 11 control rats that did not undergo operation. RESULTS: Bladder
      carcinoma failed to be found in the transplanted small intestine mucous membrane
      in all experimental rats except one. After stimulation of BBN, carcinoma of
      urinary bladder occurred in all rats' bladder transitional epithelium.
      CONCLUSION: 1) The carcinogenic substances in the urine of rats suffering from
      BBN-induced bladder carcinoma are carcinogenic only to bladder transitional
      epithelium and have no effect on small intestine epithelium. 2) Bladder
      transitional epithelium may be more sensitive to the urine carcinogenic
      substances and easier to be cancerized than small intestine epithelium. 3) The
      tentative idea of substitution of small intestine mucous membrane for bladder
      transitional epithelium to prevent the recurrence of bladder carcinoma is worth
      further studying.

PMID- 11825524
TI  - [Quantitative analysis of human herpes virus type 8 and expression of its genes
      in patients with multiple myeloma].
AB  - OBJECTIVE: To investigate if infection of human herpesvirus type 8 (HHV8) exists
      in Chinese patients with multiple myeloma (MM), and to identify the relationship
      between clinical manifestation and the viral load in bone marrow biopsy samples.
      METHODS: Real-time quantitative PCR was conducted to define the viral load of
      HHV8 in bone marrow biopsy samples from 23 patients with MM. Nested PCR was
      conducted to amplify the KS330(233)Bam fragment of HHV8 from peripheral blood
      mononuclear cells, bone marrow aspirates and bone marrow biopsy samples. RT-PCR
      was used to study the expression of suspected oncogenes: vIL-6 and vIRF-1 genes.
      Bone marrow biopsy samples of 5 patients with blood diseases other than MM and 5
      patients with non-blood system diseases were used as controls. PCR product of
      BCBL-1 cell line was used as positive control. RESULTS: (1) The positive rate of
      HHV8 in bone marrow biopsy samples from patients with MM was 69.6% (16/23) by
      real-time fluorescence quantitative PCR, and 82.6% (19/23) by nested-PCR. 16 bone
      marrow samples positive by fluorescence quantitative were positive too by nested
      PCR. However, 3 bone marrow samples positive by nested-PCR were negative by
      fluorescence quantative. HHV8 was positive in only one of the 25 bone marrow
      aspirates from patients with MM (4%) and in none of the 20 peripharal blood
      samples from patients with MM. PCR showed negative result in 7 bone marrow
      aspirates taken form 13 MM patients with positive result by fluorescence
      quantative PCR. HHV8 was negative in bone marrow biopsy samples from patients
      with other diseases. HHV8 was negative in the peripheral blood samples from 16 MM
      patients, among which 9 out of the 11 cases with bone marrow biopsy samples taken
      showed HHV8 positive by fluorescence quatative PCR. Bone marrow biopsy samples of
      all patients with other blood diseases and non-blood system diseases were HHV8
      negative. RT-PCR showed that among 12 MM patients the expression rate of vIRF-1
      was 83.3% (10/12), and expression rate of vIL-6 was 0. The PCR positive products
      tallied with the sequence of HHV8 DNA. Clinical analysis showed that all of the
      patients with negative results had had chemotherapy. CONCLUSION: There is a
      certain association between multiple myeloma pathogenesis and HHV8. In detection
      of HHVb, nested-PCR is more sensitive than fluorescence quantitaative PCR. The
      viral gene vILR-1 plays a certain role in the pathogenesis of MM.

PMID- 11825525
TI  - [Application of the IFN-gamma ELISPOT assay for monitoring CD8(+) T cell response
      to specific antigen from hepatocellular carcinoma patients].
AB  - OBJECTIVE: To study the specific CD8(+) T cell response to HLA-A2 binding peptide
      Flu p58-66 from HLA-A2-positive hepatocellular carcinoma patients and healthy
      donors. METHODS: The CD8(+) T cells were separated with immunobeads from PBMC of
      HCC patients and healthy donors, respectively. The irradiated autologous CD8(-)
      PBMC or isolated dendritic cells were loaded with influenza matrix peptide as
      APC. After 7 days' culture, the frequency of effector cells to secrete IFN-gamma
      in response to Flu p58-66 was detected in ELISPOT assay. RESULTS: With CD8(-)
      PBMC as APC, the frequency of effector cells to secrete IFN-gamma in response to
      Flu peptide was 22 +/- 9/well in HCC patients (n = 8) and 59 +/- 27/well in
      healthy donors (n = 12) when the effector cells were 5 x 10(4)/well (P < 0.01).
      To compare the antigen-presenting capacity of APC derived from 5 healthy donors,
      DC was better than CD8(-) PBMC. CONCLUSION: Although the frequency of specific
      effector CTL to secrete IFN-gamma in response to Flu p58 - 66 was lower in HCC
      patients than in healthy individuals, the majority of HCC patients have the
      cellular immunity specific to antigen peptides.

PMID- 11825526
TI  - [Effects of inorganic arsenicals on the methylation of p16 gene CpG islands and
      the expression of p16 gene in BEP2D cells].
AB  - OBJECTIVE: To study the effects of inorganic arsenicals on the methylation of p16
      gene CpG islands and the expression of p16 gene in BEP2D cells. METHODS: The
      methylation of p16 gene CpG islands and the expression of p16 gene in BEP2D cells
      were measured by methylation-specific PCR (MSP) and RT-PCR methods. RESULTS: (1)
      The exposure of the BEP2D cells to sodium arsenite (0.016 approximately 2
      micromol/L) or high-density sodium arsenate (80 approximately 160 micromol/L),
      but not low-density sodium arsenate (20 approximately 40 micromol/L), produced
      significant hypermethylation of p16 gene CpG islands in BEP2D cells. (2) The
      expressions of p16 gene in the groups of sodium arsenite and sodium arsenate at
      the test were lower than that of the control group, especially in the groups of
      sodium arsenite. CONCLUSIONS: Inorganic arsenicals alter the methylation patterns
      and the expression of p16 gene in BEP2D cells, which suggests that the
      hypermethylation of p16 gene CpG islands may be one of the mechanisms of
      carcinogenesis of inorganic arsenicals.

PMID- 11825527
TI  - [Comparison of (1)H MRS, PET and EEG in lateralization of temporal lobe
      epilepsy].
AB  - OBJECTIVE: To evaluate and compare the role of (1)H MRS, PET and EEG in
      lateralization diagnosis (LD) of temporal lobe epilepsy (TLE). METHODS: 15
      patients with intractable TLE verified by operation and pathology were studied.
      Before unilateral anterior temporal lobectomy, (1)H MRS, PET and EEG were
      performed for the LD of TLE. The diagnostic value of (1)H MRS, PET and EEG was
      compared based on the pathology and follow-up results. RESULTS: With video scalp
      EEG monitoring, the focus was localized in one temporal lobe for 13 patients
      among which 5 had abnormal waves conducted to the contralateral lobe.
      Intracranial EEG was performed for other 2 patients because scalp EEG failed to
      make the LD. Ultimately, partial temporal lobectomy was performed in all patients
      based on LD by scalp EEG or intracranial EEG. The pathological findings of
      operation specimens showed various degree of hippocampal sclerosis. The surgery
      was proved to be effective by follow-ups of all 15 patients, with their
      conditions controlled in 12 cases and better in two. EEG succeeded to make
      correct LD in all cases. (1)H MRS made correct LD in 12 cases (80%) and incorrect
      LD in 1 case, and failed to made LD in 2 cases. Five bilateral abnormalities
      (33%) were found by MRS. FDG-PET made correct LD in 14 cases (93%) and incorrect
      LD in 1 case, and found two cases with bilateral abnormalities (13%). CONCLUSION:
      (1)H MRS, PET and EEG are all effective means in LD of TLE. Up to now, scalp EEG
      is the first choice and continuous video EEG monitoring has its own unique
      advantage. As a kind of simple, noninvasive and objective method, MRS can be used
      as a routine examination in conjunction with conventional MRI. Although PET is
      quite sensitive, it is expensive and has a number of limitations. So it can be
      used depending on the affordability of patients or diagnostic need. Combination
      of MRI, MRS, PET and scalp EEG may improve the reliability of the LD compared
      with use of any one of them alone. While the results of these methods are
      controversial, intracranial EEG is inevitable.

PMID- 11825528
TI  - [Association between DLST gene polymorphism and Alzheimer's disease].
AB  - OBJECTIVE: To investigate the association between the polymorphic alleles of
      dihydrolipoamide succinyltransferase (DLST) gene cDNA at position A19117G in
      intron 13 and C19183T in exon 14 and the risk for sporandic Alzheimer's disease
      (SAD). METHODS: The polymorphism of DLST gene was detected using polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP) techniques in 105
      patients with sporadic Alzheimer disease and 109 normal controls. RESULTS: The
      frequency of AT/AC genotype was found to be significantly higher in SAD patients
      (21%) than in controls (10%) with an odds ratio of 2.36 (P < 0.05). The
      frequencies of AC/AC, AT/AT genotypes and AC allele were slightly decreased in
      cases with SAD as compared with controls. While the frequencies of the GC/GC
      genotype and GC allele were slightly higher in SAD patients than in controls.
      However, these differences were not statistically significant (P > 0.05).
      CONCLUSION: The AT/AC genotype of DLST gene is associated with an increased risk
      for SAD.

PMID- 11825530
TI  - [Posterior interbody fusion or posterolateral fusion for discogenic low back
      pain].
AB  - OBJECTIVE: To investigate the surgical results of posterior interbody fusion or
      posterolateral fusion for discogenic low back pain. METHODS: Thirty-two patients
      suffering from lumbar discogenic pain were randomly divided into two groups, one
      group undergoing posterior interbody fusion with cage (cage group, 17 patients),
      the other group undergoing posterolateral lumbar fusion with RF fixation (RF
      group, 15 patients). Low back pain improvement and lumbar fusion rate were
      followed up for at least two years. RESULTS: The low back pain improvement rate
      was 87% in cage group, and 76% in RF group one year after surgery. Pain
      improvement rate was up to 89% in cage group, and 81% in RF group two years after
      surgery. A solid arthrodesis rate was 88% in cage group and 87% in RF group one
      year after surgery, and was up to 92% in cage group, and 90% in RF group two
      years after surgery. CONCLUSION: Posterior interbody fusion for lumbar discogenic
      pain have a better clinical result than posterolateral fusion for discogenic low
      back pain. Interbody fusion is of choice for lumbar discogenic pain.

PMID- 11825529
TI  - [Association of tumor necrosis factor microsatellite polymorphism with chronic
      atrophic gastritis and gastric adenocarcinoma].
AB  - OBJECTIVE: To investigate whether TNFd and TNFe microsatellite polymorphisms
      correlate with chronic atrophic gastritis and gastric adenocarcinoma in Chinese
      Han population. METHODS: In 164 healthy controls, 53 patients with chronic
      atrophic gastritis, and 56 patients with gastric adenocarcinoma, TNFd and TNFe
      microsatellite alleles were typed using PCR technique, followed by high-voltage
      denaturing PAGE, with silver staining. At the same time, the PCR products were
      cloned and sequenced. RESULTS: Fight alleles at the TNFd locus and four alleles
      at the TNFe locus were detected. A new allele was found and identified, its
      accession number of Genebank is AF315593. Statistical analysis showed that there
      existed a very strong linkage equilibrium between TNFd8 and TNFe4 allele. No
      difference was observed between patients and healthy controls in the distribution
      of alleles at the TNFd and TNFe loci (P > 0.05). The frequence of d2/d6 genotype
      was significantly higher in patients with gastric adenocarcinoma than in healthy
      individuals (P = 0.028). d2/d6 genotype wasn't related to age or gender or grade
      of differentiation or clinicopathologic stage in gastric adenocarcinoma.
      CONCLUSION: d8e4 haplotype appears to be specific of Chinese population. d2/d6
      genotype is associated with the susceptibility to gastric adenocarcinoma.

PMID- 11825531
TI  - [Clinical analysis of pulmonary lymphangioleiomyomatosis].
AB  - OBJECTIVE: To study the clinical features, treatment, and prognosis of pulmonary
      lymphangioleiomyomatosis (LAM). METHODS: A retrospective analysis of 16 cases of
      LAM was made, among which two were diagnosed and treated in the Chinese PLA
      General Hospital, and the clinical data of the other fourteen cases were studied
      by literature review. RESULTS: Among the 16 patients, 15 were female (94%) and 1
      was male (6%). The age of onset ranged 5 - 69 years, with an average age of onset
      of 35 +/- 15 years. Thirteen patients (81%) were women of childbearing age. The
      main clinical menifestations included dyspnea (15 cases, 94%), hemoptysis (10
      cases, 62%), pneumothorax (7 cases, 44%), and chylothorax (7 cases, 44%). High
      resolution computerized tomography conducted in 14 cases showed thin-walled air
      filled cysts throughout both lungs. Seven patients took pulmonary function test
      with the results of obstructive ventilatory disturbance in 5 cases, mixed
      ventilatory disturbance in 2 cases, and reduction of carbon dioxide duffusing
      capacity in all cases. Arterial blood gas analysis was made among 11 patients and
      showed hypoxemia (blood oxygen < 80 mm Hg) in 8 cases and respiratory failure in
      5 cases. All of the patients were misdiagnosed as other diseases at the first
      visit. The time between onset of symptoms and confirmation of diagnosis ranged 2 
      276 months (median 28 months). Six patients were treated with
      medroxyprogesterone for 6-50 months. Among them two patient' condition remained
      stable, two patients' condition was worsened, and two died. Six out of the 16
      patients (38%) died of respiratory failure, pneumothorax, or lung infection 1.5
      to 26 years after the onset. CONCLUSION: The main clinical manifestations of LAM
      are dyspnea, hemoptysis, pneumothorax, and chylothorax. Medroxyprogesterone is of
      little curative effect on LAM. The main task in LAM research is to find out its
      etiology and effective treatment.

PMID- 11825532
TI  - [Persistent ectopic pregnancy, report of seven cases].
AB  - OBJECTIVE: To investigate and evaluate the occurrence, diagnosis and treatment of
      persistent ectopic pregnancy. METHODS: 411 patients with ectopic pregnancy
      treated via laparoscopy or laparotomy between July 1995 and June 2000 were
      reviewed. The clinic manifestations of patients who were successfully treated by
      laparoscopic surgery and those with persistent ectopic pregnancy were analyzed by
      multivariate stepwise logistic regression. RESULTS: Seven cases with persistent
      ectopic pregnancy occurred after laparoscopic surgery with an incidence rate of
      3.5%. Six cases had been treated by conservative approach and one case by
      tubectomy. Persistent ectopic pregnancy was diagnosed in two cases because of
      abdominal pain and intra-abdominal hemorrhage and in five cases because of
      plateauing beta-hCG titers. Two of the seven cases underwent a second time
      laparoscopic surgery and five were treated with methotrexate. The size of ectopic
      mass and the absence of villi by pathologic finding were relevant factors of
      persistent ectopic pregnancy. CONCLUSION: Small mass of ectopic pregnancy, short
      amenorrhea time, and biopsy specimens in which no villi are found are all warning
      indicators of persistent ectopic pregnancy. Close postoperative beta-hCG
      surveillance is critical for diagnosis and treatment.

PMID- 11825533
TI  - [Diagnosis and treatment of hypoglossal neurinoma].
AB  - OBJECTIVE: To investigate the symptoms, diagnosis, operative approaches and
      prognosis of hypoglossal neurinoma. METHODS: The clinical symptoms, radiological
      features, prevalence, operative approaches and prognosis of 9 cases of
      hypoglossal neurinoma were analyzed. RESULTS: Cases of neurinoma of the
      hypoglossal nerve accounted for 1.9% of the cases of skull base neoplasm in the
      same period. Most of the tumor was in the shape of dumbbell, involving both
      intracranial and extracranial segments of the nerve. In a few cases, the tumor
      mainly involved the intracranial segment of hypoglossal nerve. All the cases were
      operated on, of which 7 through extreme-far-lateral approach, 1 through extreme
      far-lateral approach combined with cervical approach, and one through the midline
      approach. Total resection was achieved in all cases. Follow up was performed in 7
      cases, among which 5 cases returned to their work, 1 resumed the ability of self
      care, and one still required care of others. CONCLUSION: As the hypoglossal canal
      is next to the jugular foramen and foramen magnum, preoperative diagnosis of the
      hypoglossal neurinoma is difficult. The most common initial symptom is atrophy of
      tongue muscle. Radical resection is the best choice of treatment. The extrem-far
      lateral approach is the best approach for operation. The prognosis is inspiring
      after operation.

PMID- 11825534
TI  - [Electrophsiological study of rabbits with axonal form Guillain-Barre syndrome].
AB  - OBJECTIVE: To investigate the electrophysiological changes of common pheroneal
      nerve in rabbit model of axonal form of Guillain-Barre syndrome (GBS). METHODS:
      Lipopolysaccaride (LPS) was inoculated into six rabbits. Three of them got GBS
      and three remained healthy. The motor nerve conduction velocity of common
      peroneal nerve, compound muscle action potential, and latency of F wave were
      determined, and electromyography of anterior tibial muscle was made in the 3
      rabbits modal of axonal form GBS, the 3 rabbits without symptom after inoculation
      of LPS, and 8 control rabbits. RESULTS: The three rabbits with axonal form GBS
      showed normal motor nerve conduction velocity and normal latency of F waves, and
      remarkably reduced compound muscle action potential amplitudes. Needle
      electromyography of anterior tibial muscle showed fibrillations and positive
      sharp waves. CONCLUSION: The electrophysiological characters of rabbits with
      axonal form GBS are consistent with those of patients with axonal form GBS.
      Electrophysiology plays an important role in diagnosing axonal form GBS.

PMID- 11825535
TI  - Hepatorenal syndrome-pathogenesis and treatment.

PMID- 11825537
TI  - The HCV and HIV coinfected patient: what have we learned about pathophysiology?
AB  - Hepatitis C virus (HCV) infection is an important problem in individuals who are
      also infected with HIV. HCV infection is very common in HIV-infected individuals,
      occurring in approximately one quarter to one third of this group, presumably as
      a consequence of shared routes of transmission related to virologic and
      pathogenic aspects of the viral infections. Although both are single-stranded RNA
      viruses and share similar epidemiologic properties, there are many important
      differences. Although the quantity of HIV RNA in plasma is an important
      prognostic determinant of HIV infection, this has not been shown with HCV. A
      direct relationship is apparent between HIV-related destruction of CD4 cells and
      the clinical consequences of the disease resulting from immunodeficiency. The
      pathogenesis of HCV, which occurs as a consequence of hepatic fibrosis, is much
      more complex. The hepatic stellate cell, the major producer of the extracellular
      matrix protein, is the main contributor to hepatic fibrosis, but the mechanism by
      which HCV induces hepatic fibrosis remains unclear. Treatment of HCV is
      increasingly important in HIV-infected patients due to improved HIV-associated
      morbidity and mortality and due to the frequency with which HCV occurs in
      patients with HIV-HCV coinfection. Timing of treatment initiation, management of
      side effects, and possible effects of anti-HCV therapy on HIV are among the
      issues that need consideration. Also, because several issues concerning HCV are
      unique to coinfected patients, further research is needed to determine optimal
      management of HCV in this setting.

PMID- 11825538
TI  - Treatment of chronic hepatitis C with PEGylated interferon and ribavirin.
AB  - Treatment with interferon alfa combined with ribavirin is successful in
      approximately 40% to 45% of patients with chronic hepatitis C viral infection
      (HCV). However, response rates are disappointing in patients who are difficult to
      treat, such as those infected with HCV genotype 1, high viral load, or advanced
      liver fibrosis. In addition, low tolerability and significant side effects of
      therapy frequently lead to dose reduction and treatment discontinuation,
      decreasing response rates further. Thus, investigation of new treatment options
      and innovations for chronic HCV infection are vital. This review describes recent
      advances in the treatment of HCV infection with PEGylated interferon (interferon
      modified with polyethylene glycol [PEG] ) combined with ribavirin.

PMID- 11825539
TI  - Evolving pathophysiologic concepts in nonalcoholic steatohepatitis.
AB  - Nonalcoholic steatohepatitis (NASH) is increasingly recognized as a relatively
      prevalent disorder (ie, occurring in 3% of adults) that may progress to cirrhosis
      in 15% to 40% of those who are afflicted. NASH is a subset of a broader
      diagnostic category, nonalcoholic fatty liver disease, a term applied to a
      condition involving the presence of excess fat in the liver with or without
      inflammation and cellular injury. A diagnosis of NASH is established by the
      presence of morphologic changes on liver biopsy similar to those seen in
      alcoholic hepatitis, including hepatocellular fat accumulation, evidence of
      lobular inflammation and cell injury, and in some cases, progressive fibrosis.
      Obesity and type 2 diabetes, two conditions associated with insulin resistance,
      are major risk factors for the development of NASH. Accumulating evidence
      suggests that the hyperinsulinemia associated with insulin resistance may be
      important in the pathogenesis of NASH. Clinical trials will now determine whether
      treatment of insulin resistance is an effective therapy for NASH.

PMID- 11825540
TI  - Use of ursodeoxycholic acid in patients with liver disease.
AB  - Ursodeoxycholic acid (UDCA), the 7beta-epimer of chenodeoxycholic acid, has
      multiple hepatoprotective activities. UDCA modifies the bile acid pool,
      decreasing levels of endogenous, hydrophobic bile acids while increasing the
      proportion of nontoxic hydrophilic bile acids. UDCA has a choleretic effect,
      increasing hepatocellular bile acid excretion, as well as cytoprotective,
      antiapoptotic, and immunomodulatory properties. UDCA has been shown to delay
      development of gastroesophageal varices and progression to cirrhosis as well as
      to improve long-term survival in patients with primary biliary cirrhosis.
      Significant improvement of abnormal liver tests may be achieved during UDCA
      therapy in patients with primary sclerosing cholangitis, intrahepatic cholestasis
      of pregnancy, cystic fibrosis-associated liver disease, nonalcoholic fatty liver
      disease, graft-versus-host disease of the liver, total parenteral nutrition
      induced cholestasis, and in some pediatric cholestatic liver diseases. However,
      unlike the effects of UDCA in primary biliary cirrhosis, the long-term effects of
      UDCA in disease progression and survival in these other conditions remain to be
      established.

PMID- 11825541
TI  - Primary biliary cirrhosis: new thoughts on pathophysiology and treatment.
AB  - Primary biliary cirrhosis (PBC) is an idiopathic inflammatory hepatic disorder
      characterized by granulomatous destruction of small bile ducts and formation of
      antimitochondrial antibodies. Having found that most patients with PBC have
      antibody reactivity to retroviral proteins, we recently cloned a retroviral
      sequence directly from biliary epithelium extracted from PBC livers. Further
      evidence for an infectious etiology of PBC has been derived from an in vitro
      model using normal biliary epithelial cells in culture with lymph node extracts
      from patients with chronic liver disease. In this model, biliary epithelial cells
      cocultivated with PBC lymph nodes developed a specific phenotype of PBC with
      immunohistochemical evidence of antimitochondrial antibody reactivity. This model
      has been used to show that patients with PBC harbor a transmissible agent that
      may be related to the cloned retrovirus. Pilot studies using antiretroviral
      treatment for patients with PBC have also supported the involvement of a
      retrovirus in the disease process. Because the antiretroviral therapy was
      tolerated without undue adverse events, a multicenter controlled trial is being
      established to determine whether patients with PBC derive significant benefit
      from this new line of investigation and management.

PMID- 11825542
TI  - Treatment of hepatitis B and C following liver transplantation.
AB  - Advanced liver disease from hepatitis B virus (HBV) and hepatitis C virus (HCV)
      is the leading indication for orthotopic liver transplantation (OLT) worldwide.
      Our understanding of recurrent liver disease related to HBV and HCV in the
      setting of OLT has evolved rapidly in the past decade. Recurrent viral hepatitis
      may lead to graft failure, death, or the need for retransplantation. Until about
      a decade ago, HBV was considered a contraindication to OLT due to its frequent
      recurrence and development of associated liver disease. Medical therapy with
      hepatitis B immune globulin and nucleoside analogues has diminished the risk of
      HBV recurrence and led to improvement in patient and graft survival.
      Consequently, OLT is now considered to be the standard of care in patients with
      end-stage liver disease related to HBV. HCV recurrence after OLT is almost
      universal. Although short-term survival in patients undergoing OLT for HCV is
      similar to survival for those transplanted for other indications, recurrent HCV
      may have an impact on long-term patient and graft survival. A specific and
      effective therapy has not been defined for recurrent HCV following
      transplantation, but the combination of interferon and ribavirin appears
      promising. Optimal strategies to eradicate these viruses or to slow disease
      progression are continually being investigated in light of the disparity between
      supply and demand in a diminishing organ pool for OLT candidates.

PMID- 11825544
TI  - The role of endoscopic ultrasound in hepatobiliary disease.
AB  - The evaluation of hepatobiliary disease continues to change as new technologies
      are introduced. One of the more recent advances in hepatobiliary imaging has been
      the application of endoscopic ultrasound (EUS). Endoscopic retrograde
      cholangiopancreatography, computed tomography, conventional ultrasound, and
      magnetic resonance imaging were previously the primary means of evaluating
      hepatobiliary disease. The role of EUS as both a substitute and a complement for
      these historical imaging modalities continues to evolve. This review examines the
      current literature on EUS in the evaluation of hepatobiliary diseases, including
      choledocholithiasis, microlithiasis, biliary strictures, obstructive jaundice,
      cholangiocarcinoma, gallbladder polyps, and liver lesions.

PMID- 11825543
TI  - How will we use the new antiviral agents for hepatitis B?
AB  - There are two licensed drugs for chronic hepatitis B virus (HBV), interferon alfa
      and lamivudine, with similar efficacy rates. Lamivudine is less expensive and
      better tolerated than interferon alfa and is the drug of choice for patients with
      decompensated cirrhosis and recurrent HBV infection after liver transplantation.
      The major problem with lamivudine monotherapy has been the emergence of drug
      resistant HBV polymerase (YMDD) mutants. Thus, long-term use of lamivudine in
      other settings remains somewhat controversial. Alternative nucleoside analogues
      that are active against both wild-type and YMDD-mutant HBV are currently being
      tested. It is hoped that a combination of one or more of these agents with
      lamivudine will not only prove more effective than lamivudine alone but also
      decrease the rate of lamivudine resistance. Preliminary studies suggest that the
      combination of interferon and lamivudine is associated with an enhanced rate of
      virologic response when compared with either agent alone. From a theoretical
      perspective, the combination of interferon with one or more nucleoside analogues
      may be the most effective way to treat HBV infection in many clinical situations.

PMID- 11825545
TI  - The impact of liver disease on health-related quality of life: a review of the
      literature.
AB  - Quality of life as an outcome variable has become an important measure in
      clinical research. Making a transition from a "biomedical model" of health to one
      that incorporates the social aspects of disease, clinicians and researchers
      dealing with chronic illness now incorporate quality-of-life measures into
      clinical practice and research. Chronic liver disease has shown a significant
      impact on the well-being of patients and contributes to the significant morbidity
      associated with these conditions. In this article, we review the recent research
      that has examined the impact of chronic liver disease on health-related quality
      of life.

PMID- 11825547
TI  - [Smoking prevalence in Catalonia (Spain), 1982-1998: a gender perspective].
AB  - BACKGROUND: We aimed at describing the smoking prevalence trend among the Catalan
      population (Spain) from 1982 to 1998, based on a gender perspective analysis.
      SUBJECTS AND METHOD: Data obtained from the surveys carried out by the Catalan
      Department of Health in 1982, 1986, 1990, 1994 and 1998 were analysed. Variables
      included were those related to smoking status, number of daily cigarettes, age
      and sex of the interviewed, type of tobacco smoked, age at which the first
      experience with smoking took place and smoking duration. Results are presented as
      proportions with 95% confidence interval and means with standard deviation.
      RESULTS: Global smoking prevalence in the 15 to 64 year-old population has
      remained stable between 1982 and 1998 (percentual variability: 1.1%). In 1998,
      there were 37.5% smokers. In women, the prevalence rate increased by 53.5% during
      the same period, reaching an overall prevalence of 30.7% in 1998. Among males,
      there was a 23.8% reduction, reaching an overall prevalence of 44.4%. The
      decreasing smoking prevalence trend observed among 15 to 24 year-old males and
      females until 1994 breaks between 1994 and 1998 so that the prevalence in young
      people increases in this period. In 1998, 26.1% women smoke light tobacco versus
      10.4% males; women smoke an average 13.8 (8.8) daily cigarettes versus 19.7
      (12.6) in males; mean smoking duration among women is 13.9 (10.1) years, while it
      is 22.6 (16.0) years among males. CONCLUSIONS: Despite the important reduction of
      smoking prevalence observed among males, the smoking prevalence rate of the
      Catalan population remains high. The situation is particularly unfavourable in
      young people of both sexes and in women, whose smoking habit has specific
      characteristics.

PMID- 11825548
TI  - [Growth retardation and nutritional status in foster children].
AB  - BACKGROUND: Our main objective was to determine growth retardation in children
      entering a foster home and catch-up growth at the end of the stay. We also
      analyzed the nutritional status and its relationship with growth retardation.
      SUBJECTS AND METHOD: Height and weight were determined in 118 children, aged
      between one month and fifteen years; they were examined at admission and at the
      time of leaving the center. In another group of 31 prepubertal children, we
      analized their nutritional status determining the body mass index, prealbumin,
      retinol binding protein, GHBP, IGF-1, IGFBP-3 and leptin at admission. RESULTS:
      31 (26.2%) out of the of the 118 children group had a height deficit (height < 2
      SDS) at admission. 32 (27.1%) of the overall group of children showed significant
      catch-up growth after their stay at the foster home, and 15 (46.8%) of them
      showed a catch-up growth > 0.5 SDS. Children below two years of age showed the
      most important growth deficit. The nutritional status study showed normal results
      in all parameters in the 31 children group. Significant correlations were
      observed between IGF-I and weight/height, IGFBP-3 and weight/height, GHBP and
      body mass index, and leptin and body mass index. CONCLUSIONS: An important
      proportion of children showed significant growth retardation at entering a foster
      home, although a significant catch-up growth was observed at the end of their
      stay. Growth failure in this population does not appear to be related to the
      nutritional status.

PMID- 11825546
TI  - Recent advances in pediatric liver transplantation.
AB  - Pediatric liver transplantation has matured into a well-established, highly
      successful treatment for advanced pediatric liver disease. Recent 1-year success
      rates range from 85% to 95%. This unprecedented achievement is the result of
      careful selection criteria and optimal timing of transplantation, technical
      advances in surgical technique, and improved treatment following transplant. This
      report highlights many recent published findings representing advances that have
      led to current successful approaches.

PMID- 11825549
TI  - [Helicobacter pylori CagA antibodies in various gastroduodenal diseases from 2
      different populations].
AB  - BACKGROUND: We aimed at studying the prevalence of infection by H. pylori along
      with the CagA status of the strain in two populations (Spain and Cuba) and the
      relationship with several gastroduodenal lesions. We also studied the role of the
      test-and-scope strategy in the decrease of unnecessary gastroscopies. PATIENTS
      AND METHOD: 100 dyspeptic patients from Spain and 100 from Cuba were included. At
      endoscopy, antrum biopsies were obtained and H. pylori status was evaluated by
      rapid urease test. CagA status of the strain was assessed by Western Blot. The
      test-and-scope strategy was evaluated according to H. pylori infection and CagA
      status. RESULTS: Mean age of Spanish and Cuban patients was 45 (16) and 46 (15)
      years, respectively. Dyspeptic symptoms were similar in both groups. Prevalence
      of infection by H. pylori was higher in Cuban (73%) than in Spaniards (40%) (p <
      0.01). Prevalence of CagA+ strains was also higher in Cuban (81 vs. 27%) (p <
      0.01). Among CagA+ Spanish patients, 11% had a duodenal ulcer, whereas this
      lesion was not found in any CagA patient (p < 0.05). Duodenal ulcer prevalence in
      CagA+ and CagA Cuban patients was 31 and 0%, respectively (p < 0.05). The test
      and-scope strategy would have avoided endoscopy in only 24% Spanish and 15% Cuban
      patients. CONCLUSIONS: The prevalence of H. pylori infection is higher in Cuban
      than in Spanish dyspeptic patients. H. pylori strains of Cuba seem to be more
      virulent than those of Spain. CagA protein is a marker of peptic ulcer in both
      populations. These differences could partly explain the variations in the
      prevalence of different gastroduodenal disorders between both countries. The test
      and-scope strategy appears to avoid a low number of endoscopies.

PMID- 11825550
TI  - [Factors which influence cardiopulmonary resuscitation and medical information
      preferences in a geriatric population].
AB  - BACKGROUND: Whether or not performing cardiopulmonary resuscitation (CPR) is a
      complex decision that requires taking account of several factors. The aim of this
      study was to analyse the preferences of elderly people with regard to CPR.
      SUBJECTS AND METHOD: Survey administered to 181 elderly subjects from nursing
      homes and ambulatory care centres. RESULTS: 66.9% of them would request
      information if hospitalised. 80.7% would wish to undergo CPR. However, this
      figure decreased to 40.9% in case of serious sequeles as a result of the
      procedure and to 32.5% in case of previous dementia. CONCLUSIONS: Request
      information would be high. Age and functional status of the elderly person

PMID- 11825551
TI  - [Hughes syndrome and thrombosis: the debate goes on].

PMID- 11825552
TI  - [Continuing medical education at a referral hospital. Quo vadis?].

PMID- 11825553
TI  - [Hereditary hemochromatosis: physiopathological, clinical and therapeutical
      considerations].

PMID- 11825554
TI  - [Hemorrhagic diathesis in a 67-year-old male with pain and limited mobility of
      the lower left limb].

PMID- 11825555
TI  - [Tacrolimus (FK506) in the treatment of prednisone-resistant myasthenia gravis.
      Preliminary results of 20 cases].

PMID- 11825556
TI  - [Gypsy offender youths: growth and nutritional status at the time of admission to
      a juvenile correctional center].

PMID- 11825557
TI  - [Non convulsive status epilepticus: exceptional first manifestation of
      hyperthyroidism].

PMID- 11825558
TI  - [Clinical trials: placebo in the treatment of osteoporosis and in the prevention
      of vertebral fractures].

PMID- 11825560
TI  - Chemokines and the tissue-specific migration of lymphocytes.
AB  - Tissue-selective trafficking of memory and effector T and B lymphocytes is
      mediated by unique combinations of adhesion molecules and chemokines. The
      discovery of several related epithelial-expressed chemokines (TECK/CCL25 in small
      intestine, CTACK/CCL27 in skin, and MEC/CCL28 in diverse mucosal sites) now
      highlights an important role for epithelial cells in controlling homeostatic
      lymphocyte trafficking, including the localization of cutaneous and intestinal
      memory T cells, and of IgA plasma cells. Constitutively expressed epithelial
      chemokines may help determine the character of local immune responses and
      contribute to the systemic organization of the immune system.

PMID- 11825561
TI  - Developing a taste for sweets.
AB  - Lymphocytes are covered with sugars. Some of the oligosaccharides on lymphocytes
      may be recognized by specific lectins such as the selectins, but what other
      functions do all of these oligosaccharides serve? Two recent papers in Cell
      (Moody et al., 2001) and Immunity (Daniels et al., 2001) describe a novel role
      for glycosylation in the thymus--regulating the interaction of MHC class I
      molecules with CD8 during thymocyte maturation.

PMID- 11825563
TI  - Cytotoxic T lymphocyte antigen-4 accumulation in the immunological synapse is
      regulated by TCR signal strength.
AB  - CD28 and CTLA-4 engagement with B7 expressed by APCs generates critical
      regulatory signals for T cell activation. CD28 is expressed on the T cell surface
      and enhances T cell expansion, while CTLA-4 localizes primarily to an
      intracellular compartment and inhibits T cell proliferation. We demonstrate that
      CTLA-4 has several unique trafficking properties that may regulate its ability to
      attenuate a T cell response. Importantly, accumulation of CTLA-4 at the
      immunological synapse is proportional to the strength of the TCR signal,
      suggesting that cells receiving stronger stimuli are more susceptible to CTLA-4
      mediated inhibition. This may represent a novel feedback control mechanism in
      which a stimulatory signal regulates the recruitment of an inhibitory receptor to
      a functionally relevant site on the cell surface.

PMID- 11825562
TI  - Helix-loop-helix proteins regulate pre-TCR and TCR signaling through modulation
      of Rel/NF-kappaB activities.
AB  - E2A and HEB are basic helix-loop-helix transcription factors essential for T cell
      development. Complete inhibition of their activities through transgenic
      overexpression of their inhibitors Id1 and Tal1 leads to a dramatic loss of
      thymocytes. Here, we suggest that bHLH proteins play important roles in
      establishing thresholds for pre-TCR and TCR signaling. Inhibition of their
      function allows double-negative cells to differentiate without a functional pre
      TCR, while anti-CD3 stimulation downregulates bHLH activities. We also find that
      the transcription factor NF-kappaB becomes activated in transgenic thymocytes.
      Further activation of NF-kappaB exacerbates the loss of thymocytes, whereas
      inhibition of NF-kappaB leads to the rescue of double-positive thymocytes.
      Therefore, we propose that E2A and HEB negatively regulate pre-TCR and TCR
      signaling and their removal causes hyperactivation and apoptosis of thymocytes.

PMID- 11825564
TI  - A CD40 Signalosome anchored in lipid rafts leads to constitutive activation of NF
      kappaB and autonomous cell growth in B cell lymphomas.
AB  - B cell lineage non-Hodgkin's lymphomas (NHL-B) are neoplastic B cells that show
      dysregulated B lymphocyte growth characteristics. Unlike normal B cells,
      aggressive NHL-B cells show constitutive expression of nuclear NF-kappaB by
      maintaining an assembled, scaffold-like signaling platform, called a Signalosome
      within the lipid raft microdomain, extending from the cell membrane. The CD40
      Signalosome appears to be initiated through autochthonous production and cognate
      binding of CD154 (CD40L, gp39) to CD40 by the lymphoma cell. Constitutive
      expression of NF-kappaB in NHL-B can be downregulated by treatment with
      antibodies to CD40 or CD154 that disrupt Signalosomes, inhibit lymphoma cell
      growth, and induce cell death. CD40 Signalosomes may provide a potentially
      vulnerable target for therapeutic intervention in NHL-B cells.

PMID- 11825565
TI  - Activation of the PKB/AKT pathway by ICAM-2.
AB  - We identified intracellular adhesion molecule-2 (ICAM-2) in a genetic screen as
      an activator of the PI3K/AKT pathway leading to inhibition of apoptosis. ICAM-2
      induced tyrosine phosphorylation of ezrin and PI3K kinase membrane translocation,
      resulting in phosphatidylinositol 3,4,5 production, PDK-1 and AKT activation, and
      subsequent phosphorylation of AKT targets BAD, GSK3, and FKHR. ICAM-2 clustering
      protected primary human CD19+ cells from TNFalpha- and Fas-mediated apoptosis as
      determined by single-cell analysis. ICAM-2 engagement by CD19+ cells of its
      natural receptor, LFA-1, on CD4+ naive cells specifically induced AKT activity in
      the absence of an MHC-peptide interaction. These results attribute a novel
      signaling function to ICAM-2 that might suggest mechanisms by which ICAM-2
      signals intracellular communication at various immunological synapses.

PMID- 11825566
TI  - CXCL13 is required for B1 cell homing, natural antibody production, and body
      cavity immunity.
AB  - B1 cells are a predominant cell type in body cavities and an important source of
      natural antibody. Here we report that in mice lacking the chemokine, CXCL13, B1
      cells are deficient in peritoneal and pleural cavities but not in spleen. CXCL13
      is produced by cells in the omentum and by peritoneal macrophages, and in
      adoptive transfers, B1 cells home to the omentum and the peritoneal cavity in a
      CXCL13-dependent manner. CXCL13(-/-) mice are deficient in preexisting
      phosphorylcholine (PC)-specific antibodies and in their ability to mount an anti
      PC response to peritoneal streptococcal antigen. These findings provide insight
      into the mechanism of B1 cell homing and establish a critical role for B1 cell
      compartmentalization in the production of natural antibodies and for body cavity
      immunity.

PMID- 11825567
TI  - Crystal structures of RAE-1beta and its complex with the activating
      immunoreceptor NKG2D.
AB  - Induced by retinoic acid and implicated in playing a role in development, rodent
      RAE-1 proteins are ligands for the activating immunoreceptor NKG2D, widely
      expressed on natural killer cells, T cells, and macrophages. RAE-1 proteins
      (alpha, beta, gamma, and delta) are distant major histocompatibility complex
      (MHC) class I homologs, comprising isolated alpha1alpha2 platform domains. The
      crystal structure of RAE-1beta was distorted from other MHC homologs and
      displayed noncanonical disulfide bonds. The loss of any remnant of a peptide
      binding groove was facilitated by the close approach of the groove-defining
      helices through a hydrophobic, leucine-rich interface. The RAE-1beta-murine NKG2D
      complex structure resembled the human NKG2D-MICA receptor-ligand complex and
      further demonstrated the promiscuity of the NKG2D ligand binding site.

PMID- 11825568
TI  - Disulfide bond isomerization and the assembly of MHC class I-peptide complexes.
AB  - The presence of a disulfide bond inside the peptide binding groove of MHC class I
      molecules and of the thiol oxidoreductase ERp57 in the class I loading complex
      suggests that disulfide bond isomerization may play a role in peptide loading.
      Here we show that ERp57 and tapasin are disulfide linked inside the loading
      complex. Mutagenesis of cysteine 95 in tapasin not only abolishes formation of
      the ERp57-tapasin bond but also prevents complete oxidation of the class I heavy
      chain in the loading complex. The resulting MHC class I-beta2m heterodimers are
      poorly loaded with high-affinity peptides in the ER but nevertheless escape to
      the cell surface where they are unstable. These findings suggest a role for
      disulfide bond isomerization in tapasin-mediated peptide loading.

PMID- 11825569
TI  - Assembly and antigen-presenting function of MHC class I molecules in cells
      lacking the ER chaperone calreticulin.
AB  - MHC class I molecules expressed in a calreticulin-deficient cell line (K42)
      assembled with beta 2-microglobulin (beta2-m) normally, but their subsequent
      loading with optimal peptides was defective. Suboptimally loaded class I
      molecules were released into the secretory pathway. This occurred despite the
      ability of newly synthesized class I to interact with the transporter associated
      with antigen processing (TAP) loading complex. The efficiency of peptide loading
      was reduced by 50%-80%, and impaired T cell recognition was observed for three
      out of four antigens tested. The peptide-loading function was specific to
      calreticulin, since the defect in K42 could be rectified by transfection with
      calreticulin but not a soluble form of calnexin, which shares its lectin-like
      activity.

PMID- 11825570
TI  - Dynamic polarization of the microtubule cytoskeleton during CTL-mediated killing.
AB  - Efficient unidirectional killing by cytotoxic T lymphocytes (CTL) requires
      translocation of the microtubule organizing center (MTOC) to the target cell
      contact site. Here we utilize modulated polarization microscopy and computerized
      3D reconstruction of tubulin and LFA-1 immunofluorescence images to investigate
      how this is accomplished. The results show that the MTOC is drawn vectorially to
      the contact site by a microtubule sliding mechanism. Once the MTOC arrives at the
      contact site, it oscillates laterally. Microtubules loop through and anchor to a
      ring-shaped zone (pSMAC) defined by the dense clustering of LFA-1 at the target
      contact site. Microtubules that run straight between the MTOC and pSMAC and then
      turn sharply may indicate the action of a microtubule motor such as dynein.

PMID- 11825571
TI  - Effects of sequence and structure on the hypermutability of immunoglobulin genes.
AB  - Somatic hypermutation (SHM) is investigated in related immunoglobulin transgenes
      that differ in a short artificial sequence designed to vary the content of
      hotspot motifs and the potential to form RNA or DNA secondary structures.
      Mutability depends on hotspots, not secondary structure. Hotspot motifs predict
      about 50% of the mutations; the rest are in neutral and coldspots. Clusters of
      mutations and the sequential addition of mutations found in cell pedigrees
      suggest epigenetic attributes of SHM. Sometime in SHM, an essential factor seems
      to become limiting. Particular error-prone DNA polymerases appear to create
      mutations in hotspots on the top and bottom DNA strands throughout the target and
      the SHM process. One transgene is superhypermutable in all regions, suggesting
      the presence of a cis-element that enhances SHM.

PMID- 11825572
TI  - DC-SIGN-mediated internalization of HIV is required for trans-enhancement of T
      cell infection.
AB  - Fusion of the human immunodeficiency virus (HIV) to the plasma membrane of target
      cells is mediated by interaction of its envelope glycoprotein, gp120, with CD4
      and appropriate chemokine receptors. gp120 additionally binds to DC-SIGN, a C
      type lectin expressed on immature dendritic cells. This interaction does not
      result in viral fusion, but instead contributes to enhanced infection in trans of
      target cells that express CD4 and chemokine receptors. Here we show that DC-SIGN
      mediates rapid internalization of intact HIV into a low pH nonlysosomal
      compartment. Internalized virus retains competence to infect target cells.
      Removal of the DC-SIGN cytoplasmic tail reduced viral uptake and abrogated the
      trans-enhancement of T cell infection. We propose that HIV binds to DC-SIGN to
      gain access to an intracellular compartment that contributes to augmentation or
      retention of viral infectivity.

PMID- 11825573
TI  - HIV-1 Nef-induced upregulation of DC-SIGN in dendritic cells promotes lymphocyte
      clustering and viral spread.
AB  - DC-SIGN, a dendritic cell (DC)-specific lectin, mediates clustering of DCs with T
      lymphocytes, a crucial event in the initiation of immune responses. DC-SIGN also
      binds HIV envelope glycoproteins, allowing efficient virus capture by DCs. We
      show here that DC-SIGN surface levels are upregulated in HIV-1-infected DCs. This
      process is caused by the viral protein Nef, which acts by inhibiting DC-SIGN
      endocytosis. Upregulation of DC-SIGN at the cell surface dramatically increases
      clustering of DCs with T lymphocytes and HIV-1 transmission. These results
      provide new insights into how HIV-1 spreads from DCs to T lymphocytes and
      manipulates immune responses. They help explain how Nef may act as a virulence
      factor in vivo.

PMID- 11825574
TI  - Agonist-induced vasoactive responses in isolated perfused porcine dental pulpal
      arterioles.
AB  - A novel isolated perfused pulpal arteriole preparation and microperfusion system
      was used to evaluate the direct vasoactive responses of pulpal arterioles to
      selected agonists. Short lengths of porcine pulpal arterioles (101.7+/-2.2 microm
      o.d., n=105) were dissected out and placed in an environment-controlled bath on
      the stage of an inverted microscope. Both ends of the vessel were cannulated and
      perfused at a controlled rate through the lumen. The diameter of the vessel was
      measured online. Following equilibration, the vessel was challenged with various
      agonists: adrenaline (epinephrine), noradrenaline (norepinephrine),
      phenylephrine, dopamine, isoproterenol, 5-hydroxytryptamine, histamine and
      adenosine. The endothelium-dependent vasodilator acetylcholine was used to
      evaluate endothelial cell function. Adrenaline, noradrenaline, phenylephrine, 5
      hydroxytryptamine and dopamine caused dose-dependent contractions
      (adrenaline=noradrenaline>phenylephrine>dopamine>5-hydroxytryptamine).
      Isoproterenol and histamine provoked a dose-dependent dilation. Adenosine
      produced pronounced vasodilatation in vessels precontracted with 10(-8)M
      endothelin-1. Functional adrenergic, histamine, 5-hydroxytryptamine and adenosine
      receptors are, therefore, present in porcine pulpal arterioles. The isolated
      perfused pulpal arteriole preparation may prove valuable in understanding local
      control mechanisms of pulpal microcirculation.

PMID- 11825575
TI  - Effects of diet consistency on the myosin heavy chain mRNAs of rat masseter
      muscle during postnatal development.
AB  - To study the effects of diet consistency on the fiber phenotypes of rat masseter
      (1-70 days of age), the mRNAs of myosin heavy chain isoforms (MHC embryonic,
      neonatal, I, IIa, IId/x and IIb) were measured in total RNA preparations from
      masseters of hard-diet group (HDG) and soft-diet group (SDG) by competitive
      reverse transcriptase-polymerase chain reaction (RT-PCR). With respect to the
      time course of the transition of each MHC mRNA expressed as a percentage relative
      to the maximum mean, the soft diet facilitated early (9 days after weaning)
      expression of IId/x and IIb isoforms, and also a decline in the expression of
      neonatal and IIa isoforms. The expression of neonatal, IIa and IId/x isoforms at
      70 days of age was significantly (P<0.05, P<0.01, P<0.01, respectively) lower in
      SDG than in HDG, indicating a higher relative composition of the IIb isoform in
      the SDG. Embryonic MHC mRNA had disappeared by 14 days of age (i.e. before
      weaning at 19 days). No MHC I mRNA was observed in any masseter studied. These
      results suggest that in the rat a soft diet facilitates an even more MHC IIb-rich
      phenotype in the masseter muscle than a hard diet.

PMID- 11825576
TI  - Inhibitory effect of ZnCl(2) on glycolysis in human oral microbes.
AB  - Although the inhibition of bacterial glycolysis by zinc ions might be expected to
      moderate dental caries, there has not been a comparison of the effect of Zn on
      different organisms under both fixed pH and free-fall conditions. Here, the
      effect of ZnCl(2) on Streptococcus salivarius, Strep. mutans, Strep. sobrinus,
      Actinomyces naeslundii and Lactobacillus casei, as well as on mixtures of oral
      organisms outgrown from human dental plaque and saliva, was surveyed. pH-stat
      experiments were performed at pH 7, 6 or 5 in a solution containing 5% glucose
      and a suspension of the test organism; pH-fall experiments started at pH 7. In
      both cases, acid production was monitored for 60 min, when samples were taken for
      Zn and lactate determinations. Under pH-stat conditions, acid production was
      inhibited by Zn most strongly in Strep. sobrinus and Strep. salivarius. In terms
      of total acid production averted, however, the effect of Zn under both pH-stat
      and pH-fall conditions was clearly greatest with Strep. salivarius. A. naeslundii
      was inhibited the least strongly under pH-stat conditions. Cultured oral organism
      mixtures were more sensitive to moderate concentrations of zinc (0.2-0.3mM
      initial concentration) than were the single species to higher concentrations
      (1mM). Packed cell layers responded to Zn quite differently from suspensions, the
      pH often falling in the presence of 1mM Zn at a rate similar to the no Zn
      control. As streptococci had the highest acidogenesis rates in both pH-stat and
      pH-fall experiments, it seems likely that inhibition of acid production with
      these organisms would be of more value in moderating caries than the inhibition
      of less acidogenic organisms such as A. naeslundii.

PMID- 11825577
TI  - Dependence of pulpal blood-flow responses on baseline blood-flow in the cat.
AB  - It has been shown earlier that electrical stimulation of the distal cut end of
      the inferior alveolar nerve (IAN) in the cat evokes three different patterns of
      pulpal blood-flow (PBF) response in the ipsilateral mandibular canine tooth (a
      decrease, a biphasic response, or an increase). The response to a given stimulus
      sometimes changed to another pattern even in one and the same experimental animal
      during the course of the experiment. It is known that the evoked decrease is due
      to activation of the sympathetics and that the increase is due to antidromic
      activation of sensory fibres; but, it is unknown why the response varies so much.
      It is hypothesised that the baseline blood-flow (BBF) modulates vasomotor
      responses in the dental pulp. To test this hypothesis, the effects of BBF on PBF
      responses elicited by the IAN stimulation mentioned above were investigated.
      Dynamic changes in PBF in cat mandibular canine teeth were elicited by electrical
      stimulation of the distal cut end of the IAN, at various BBF, with blood-flow
      monitored by laser Doppler flowmetry. The amplitude of the PBF vasodilator
      response increased as BBF was adjusted downwards (by cooling the tooth). In
      contrast, the amplitude of the PBF vasoconstrictor response increased as the BBF
      rose. Vasodilator responses could be transformed into vasoconstrictor responses,
      and vice versa, by alterations in the BBF. No systemic blood-pressure changes
      were elicited throughout the experiment. These results indicate that a
      consideration of baseline vascular tone is important, whenever the size of PBF
      responses to various stimuli is discussed or calculated.

PMID- 11825578
TI  - Viscoelastic properties and residual strain in a tensile creep test on bovine
      temporomandibular articular discs.
AB  - This study was designed to evaluate the creep characteristics and residual strain
      of bovine temporomandibular joint (TMJ) discs in tension. Twenty discs were
      divided into three specimens each: central, lateral and medial regions. Tension
      of 1.0 MPa was applied and sustained for 20 min to the specimens from 10 right
      side discs, and tension of 1.5 MPa to specimens from 10 left-side discs. After
      the period of tension for creep, the specimens were removed from the tension
      devices and restoration observed for 20 min. Time-dependent creep curves showed a
      marked change in strain during the initial 5s. The essential time delay in strain
      ceased after 2 min, and strain reached an almost steady level after 3 min. At a
      tensile stress of 1.5 MPa, a strain of 14.5% on average was produced after 20 min
      creep in the central specimens; peripheral specimens showed strains of 12.4% on
      average. There were significant differences in strain between the central and
      peripheral specimens. The residual strain after 20 min restoration was 0.93% on
      average and there were no significant regional differences. This creep feature
      could be well represented by a generalized linear viscoelastic model. It was
      concluded that the regional differences in viscoelasticity might be caused by the
      complicated articulating functions of the TMJ, and that the residual strain
      caused by sustained stress could be an important factor in disc deformation.

PMID- 11825579
TI  - Effect of dietary carbamyl phosphate on dentine apposition in rat molars.
AB  - In rats, sucrose increases dental caries and impairs odontoblastic function by
      reducing dentine apposition during primary dentinogenesis. A high-sucrose diet
      also affects negatively a pulp or dentine function that appears to regulate
      solute or fluid movement within rat dentinal tissue. In earlier work it was found
      that carbamyl phosphate could significantly reverse sucrose-induced cariogenesis
      and also stimulate sucrose-depressed movement of dentinal fluid through a
      mechanism involving parotid function(s). In the current study, the possibility
      that carbamyl phosphate could overcome the sucrose-induced reduction in dentine
      apposition was examined. Weanling rats were fed a high-sucrose diet supplemented
      or not with carbamyl phosphate for 5 weeks. Dentine apposition was measured
      planimetrically in sagittal sections of the molars. The effect of carbamyl
      phosphate was similarly tested in parotidectomized animals. Carbamyl phosphate
      significantly reduced the deleterious effect of sucrose on dentine apposition by
      58% in the first molars. However, the reduction in dentine apposition that
      followed parotidectomy was not altered by carbamyl phosphate supplementation. The
      possibility that the beneficial effect of carbamyl phosphate on dentinogenesis
      involves a parotid function is entertained.

PMID- 11825580
TI  - Differential in vitro response to epidermal growth factor by prenatal murine
      cranial-base chondrocytes.
AB  - The retrognathic Brachyrrhine (Br) heterozygote mouse mutant has a very localized
      morphological deficiency in the sphenoethmoidal region of the anterior cranial
      base. The purpose of this study was to test the hypothesis that a primary growth
      defect occurs in that region of Br mice. Primary cell cultures were derived from
      presumptive nasal septal and sphenoethmoidal regions of Br and wild-type
      littermates. Cultures were stimulated with 1.0 ng/ml epidermal growth factor
      (EGF), and [3H]thymidine and [35S] incorporation was measured. Growth of the
      nasal septal chondrocytes did not differ significantly between groups. In the
      cultures derived from the sphenoethmoidal region [35S] incorporation was greater,
      but not significantly so, in the normal group. However, EGF did significantly
      stimulate proliferation of the sphenoethmoidal chondrocytes in wild-type cultures
      above that measured in Br cultures. Therefore, the Br genetic aberration is
      associated with a primary growth defect in the sphenoethmoidal region of the
      cranial base. These results suggest that growth of the anterior cranial base
      occurs differentially and that the defect in Br mice results in reduced
      sphenoidal but not nasal septal growth.

PMID- 11825581
TI  - Behavioral and electrophysiological consequences of deafferentation following
      chronic constriction of the infraorbital nerve in adult rats.
AB  - Deafferentation of the hind paw following sciatic nerve injury results in
      behavioral changes, such as autotomy, suggestive of persistent, spontaneous pain.
      The effects of deafferentation involving trigeminal nerves have, however,
      received less attention. Here, alterations in trigeminal ganglion neuronal
      activity and mechanically evoked and spontaneous behavior were studied in adult
      rats after a chronic constriction injury of the infraorbital nerve (ION).
      Compared to sham-operated rats, most rats with ION damage were unresponsive to
      mechanical stimulation of the mystacial vibrissae up to 56 days after surgery.
      Increased facial grooming was observed only in rats with chronic ION constriction
      10 days after surgery. Free-ranging behavior was similar to that of sham-injury
      animals. In contrast, increases in the number of spontaneously active trigeminal
      ganglion neurones were observed in those rats with ION injuries at both 3 and 56
      days. These data suggest that chronic constrictive injuries of the ION resulting
      in prolonged loss of low-threshold input from the periphery lead to only
      transient behavioral changes, despite the presence of spontaneous activity in
      trigeminal sensory neurones.

PMID- 11825582
TI  - Acidic beta-galactosidase in the developing mouse submandibular gland.
AB  - Acidic beta-galactosidase (beta-gal) is expressed at high concentrations in the
      salivary glands, where its function is unknown but probably related to lysosomal
      catabolism of glycolipids or glycoproteins such as mucin. Here, the developmental
      pattern of the enzyme activity in the submandibular gland of B10A/SGSNJ mice was
      investigated in relation to the expression of mucin. Biochemical studies
      indicated that the activity of acidic beta-gal increases significantly from birth
      to 3 weeks of age (P<0.05). Histochemical staining of the submandibular glands of
      embryonic day 15 (E15), E18, 3-week-old and adult mice showed a trend of
      increasing staining intensity accompanied by a change in the cellular
      distribution of enzyme activity from E15 to adulthood. Acidic beta-gal activity
      was first evident at E18, around the time mucin production starts, primarily in
      terminal-bud epithelial cells. The spatial and temporal coordination between the
      appearance of beta-gal and embryonic mucin in the terminal buds of acinar cells
      might be related to a role of this enzyme in lysosomal degradation of embryonic
      mucin. In contrast, in adult mice, beta-gal activity was primarily found in
      granular-duct cells. The function of beta-gal in duct cells is unclear, but the
      change in the cellular distribution of beta-gal in the mouse submandibular gland
      could reflect a change in the substrate specificity of this enzyme between E18
      and adulthood.

PMID- 11825583
TI  - Self-assembled vesicles of monocarboxylic acids and alcohols: conditions for
      stability and for the encapsulation of biopolymers.
AB  - We tested the ability of saturated n-monocarboxylic acids ranging from eight to
      12 carbons in length to self-assemble into vesicles, and determined the minimal
      concentrations and chain lengths necessary to form stable bilayer membranes.
      Under defined conditions of pH and concentrations exceeding 150 mM, an unbranched
      monocarboxylic acid as short as eight carbons in length (n-octanoic acid)
      assembled into vesicular structures. Nonanoic acid (85 mM) formed stable vesicles
      at pH 7.0, the pK of the acid in bilayers, and was chosen for further testing. At
      pH 6 and below, the vesicles were unstable and the acid was present as droplets.
      At pH ranges of 8 and above clear solutions of micelles formed. However, addition
      of small amounts of an alcohol (nonanol) markedly stabilized the bilayers, and
      vesicles were present at significantly lower concentrations (approximately 20 mM)
      at pH ranges up to 11. The formation of vesicles near the pK(a) of the acids can
      be explained by the formation of stable RCOO(-)...HOOCR hydrogen bond networks in
      the presence of both ionized and neutral acid functions. Similarly, the effects
      of alcohols at high pH suggests the formation of stable RCOO(-)...HOR hydrogen
      bond networks when neutral RCOOH groups are absent. The vesicles provided a
      selective permeability barrier, as indicated by osmotic activity and ionic dye
      capture, and could encapsulate macromolecules such as DNA and a protein. When
      catalase was encapsulated in vesicles of decanoic acid and decanol, the enzyme
      was protected from degradation by protease, and could act as a catalyst for its
      substrate, hydrogen peroxide, which readily diffused across the membrane. We
      conclude that membranous vesicles produced by mixed short chain monocarboxylic
      acids and alcohols are useful models for testing the limits of stabilizing
      hydrophobic effects in membranes and for prebiotic membrane formation.

PMID- 11825584
TI  - Entrainment in solution of an oscillating NADH oxidase activity from the bovine
      milk fat globule membrane with a temperature-compensated period length suggestive
      of an ultradian time-keeping (clock) function.
AB  - Entrainment in solution of an oscillating activity with a temperature compensated
      period of 24 min is described for a NADH oxidase (NOX) activity of the bovine
      milk fat globule membrane, a derivative of the mammary epithelial cell plasma
      membrane. The period of 24 min remained unchanged at 17 degrees C, 27 degrees C
      and 37 degrees C whereas the amplitude approximately doubled with each 10 degree
      C rise in temperature (Q(10)congruent with 2). The periodicity was observed with
      both intact milk fat globule membranes and with detergent-solubilized membranes,
      demonstrating that the oscillations did not require an association with
      membranes. The periodicity was not the result of instrument variation or of
      chemical interactions among reactants in solution. Preparations with different
      periodicities entrained (autosynchronized) when mixed. Upon mixing, the
      preparations exhibited two oscillatory patterns but eventually a single pattern
      representing the mean of the farthest separated maxima of the two preparations
      analyzed separately emerged. The cell surface NOX protein is the first reported
      example of an entrainable biochemical entity with a temperature-compensated
      periodicity potentially capable of functioning as an ultradian or circadian clock
      driver.

PMID- 11825585
TI  - P-glycoprotein inserted in planar lipid bilayers formed by liposomes opened on
      amorphous carbon and Langmuir-Blodgett monolayer.
AB  - The insertion of proteins into planar lipid layers is of outstanding interest as
      the resulting films are suitable for the investigation of protein structure and
      aggregation in a lipid environment and/or the development of biotechnological
      applications as biosensors. In this study, purified P-glycoprotein (P-gp), a
      membrane drug pump, was incorporated in model membranes deposited on solid
      supports according to the method by Puu and Gustafson, Biochim. Biophys. Acta
      1327 (1997) 149-161. The models were formed by a double lipid layer obtained by
      opening P-gp-containing liposomes onto two hydrophobic supports: amorphous carbon
      films and Langmuir-Blodgett (L-B) lipid monolayers, which were then observed by
      transmission electron microscopy and atomic force microscopy, respectively.
      Before the opening of liposomes, the P-gp structure and functionality were
      verified by circular dichroism spectroscopy and enzymatic assay. Our micrographs
      showed that liposomes containing P-gp fuse to the substrates more easily than
      plain liposomes, which keep their rounded shape. This suggests that the protein
      plays an essential role in the fusion of liposomes. To localize P-gp, the
      immunogold labeling of two externally exposed protein epitopes was carried out.
      Both imaging techniques confirmed that P-gp was successfully incorporated in the
      model membranes and that the two epitopes preserved the reactivity with specific
      mAbs, after sample preparation. Model membranes obtained on L-B monolayer
      incorporated few molecules with respect to those incorporated in the model
      membrane deposited onto amorphous carbon, probably because of the different
      mechanism of proteoliposome opening. Finally, all particles appeared as isolated
      units, suggesting that P-gp molecules were present as monomers.

PMID- 11825587
TI  - The complex of band 3 protein of the human erythrocyte membrane and
      glyceraldehyde-3-phosphate dehydrogenase: stoichiometry and competition by
      aldolase.
AB  - The cytoplasmic domain of band 3, the main intrinsic protein of the erythrocyte
      membrane, possesses binding sites for a variety of other proteins of the membrane
      and the cytoplasm, including the glycolytic enzymes glyceraldehyde-3-phosphate
      dehydrogenase (GAPDH) and aldolase. We have studied the stoichiometry of the
      complexes of human band 3 protein and GAPDH and the competition by aldolase for
      the binding sites. In addition, we have tried to verify the existence of mixed
      band 3/GAPDH/aldolase complexes, which could represent the nucleus of a putative
      glycolytic multienzyme complex on the erythrocyte membrane. The technique applied
      was analytical ultracentrifugation, in particular sedimentation equilibrium
      analysis, on mixtures of detergent-solubilized band 3 and dye-labelled GAPDH, in
      part of the experiments supplemented by aldolase. The results obtained were
      analogous to those reported for the binding of hemoglobin, aldolase and band 4.1
      to band 3: (1) the predominant or even sole band 3 oligomer forming the binding
      site is the tetramer. (2) The band 3 tetramer can bind up to four tetramers of
      GAPDH. (3) The band 3/GAPDH complexes are unstable. (4) Artificially stabilized
      band 3 dimers also represent GAPDH binding sites. In addition it was found that
      aldolase competes with GAPDH for binding to the band 3 tetramer, and that ternary
      complexes of band 3 tetramers, GAPDH and aldolase do exist.

PMID- 11825586
TI  - Utilizing temperature-sensitive association of Pluronic F-127 with lipid bilayers
      to control liposome-cell adhesion.
AB  - The temperature sensitive properties of Pluronic F-127 (MW approximately 12600,
      PEO(98)-PPO(67)-PEO(98)), a block co-polymer or poloxamer, was used to control
      liposome-cell adhesion. When associated with liposomes, the PEO moiety of the
      block co-polymer is expected to inhibit liposome-cell adhesion. Liposomes were
      made using egg phosphatidylcholine and different mole% of Pluronic F-127. Size
      measurement of the liposomes at different temperatures, in the presence and
      absence of Pluronic F-127, shows significant reduction in the size of
      multilamellar vesicles, at higher temperatures, by the Pluronic molecules.
      Negative stain electron microscopy study showed the presence of individual
      molecules and micelles of Pluronic, respectively at temperatures below and above
      the critical micellar temperature (CMT). Measurement of the surface associated
      Pluronics indicated that they associated with liposomes when the sample was
      heated above the Pluronic CMT, and dissociated from liposomes when cooled below
      the CMT. Attachment of the Pluronic containing liposomes to CHO cells was
      inhibited at temperatures above the CMT, but not at temperatures below CMT,
      indicating that temperature-sensitive control of liposome-cell adhesion is
      achieved.

PMID- 11825588
TI  - Characterization of a novel pH-sensitive peptide that enhances drug release from
      folate-targeted liposomes at endosomal pHs.
AB  - Although liposomes have proven useful for the delivery of drugs and gene therapy
      vectors, their potencies are often compromised by poor unloading following uptake
      into their target cells. We have consequently explored the properties of a novel
      29-residue amphipathic peptide that was designed by arrangement of hydrophobic
      and hydrophilic residues to disrupt liposomes at lower peptide concentrations
      than previously tested peptides. The peptide was indeed found to promote pH
      dependent liposome unloading with improved efficiency. A peptide of the same
      sequence, but half the length, however, promoted pH-dependent permeabilization
      only at much higher concentrations. Further characterization of the longer
      peptide revealed that release of liposome contents (i) occurred at a pH of
      approximately 6, (ii) became less efficient as the size of the encapsulated cargo
      increased, and (iii) was moderately suppressed in cholesterol-containing
      liposomes. Use of this peptide to enhance the cytotoxicity of cytosine
      arabinoside encapsulated in folate-targeted liposomes demonstrated an increase in
      drug potency of approximately 30-fold. Gene expression by a serum-stable folate
      targeted liposomal vector was also measurably enhanced by inclusion of the
      peptide. We conclude that intracellular unloading of liposomal contents can be
      significantly improved by co-encapsulation of an optimally designed, pH-sensitive
      peptide.

PMID- 11825589
TI  - Low-affinity Ca(2+) and Ba(2+) binding sites in the pore of alpha7 nicotinic
      acetylcholine receptors.
AB  - alpha7 nicotinic receptors are highly permeable to Ca(2+) as well as monovalent
      cations. We extended the characterization of the Ca(2+) permeation of non
      desensitizing chick alpha7 receptors (S240T/L247T alpha7 nAChRs) expressed in
      Xenopus oocytes by (1) measuring the concentration dependence of conductance
      under conditions in which Ca(2+) or Ba(2+) were the only permeant cations in the
      extracellular solution, and (2) measuring the concentration dependence of Ca(2+)
      block of K(+) currents through the receptors. The first set of experiments
      yielded an apparent affinity of 0.96 mM Ca(2+) activity (2.4 mM concentration)
      for Ca(2+) permeation and an apparent affinity of 0.65 mM Ba(2+) activity (1.7 mM
      concentration) for Ba(2+) permeation. The apparent affinity of Ca(2+) inhibition
      of K(+) currents was 0.49 mM activity (1.5 mM concentration). The similarity of
      these apparent affinities in the millimolar range suggests that the pore of
      alpha7 receptors has one or more low-affinity Ca(2+) binding sites and no high
      affinity sites.

PMID- 11825590
TI  - Potentiation of liposome-induced complement activation by surface-bound albumin.
AB  - Large anionic multilamellar liposomes containing 71% membrane cholesterol (MLV)
      caused complement (C) activation in human serum in vitro, as reflected in
      significant rises in S protein-bound terminal complex (SC5b-9) and C3a-desarg
      levels. Increasing the albumin content in serum by 1-4 g/100 ml led to 50-100%
      further increase in MLV-induced C activation, while higher amounts of exogenous
      human serum albumin (HSA) gradually lost the capability to potentiate liposomal C
      activation. HSA alone had no influence on SC5b-9 formation at any level below
      12%. Complement activation by liposomes and the potentiating effect of
      supplemental HSA were greatly reduced or eliminated in the absence of C1q or in
      the presence of 10 mM EGTA/2.5 mM Mg(2+), pointing to the involvement of the
      classical pathway. Potentiation of C activation by supplemental HSA was not
      unique to MLV-induced activation, as deposition of HSA on the membrane of
      "Centricon" ultrafiltration units also potentiated the C-activating effect of the
      polycarbonate membrane. Fatty acid (FA) or non-monomeric protein contamination in
      HSA were unlikely to be playing a role in the described effects, as 96% pure, FA
      rich (Buminate) and 99% pure, FA-free HSA had identical effects on liposomal C
      activation. While highlighting a new modulatory mechanism on liposomal C
      activation, the above data raise the possibility that deposition of extravasated
      HSA at sites of tissue injury may serve a hitherto unrecognized proinflammatory
      function.

PMID- 11825591
TI  - The adaptive dynamics of Lotka-Volterra systems with trade-offs.
AB  - We analyse the adaptive dynamics of a generalised type of Lotka-Volterra model
      subject to an explicit trade-off between two parameters. A simple expression for
      the fitness of a mutant strategy in an environment determined by the established,
      resident strategy is obtained leading to general results for the position of the
      evolutionary singular strategy and the associated second-order partial
      derivatives of the mutant fitness with respect to the mutant and resident
      strategies. Combinations of these results can be used to determine the
      evolutionary behaviour of the system. The theory is motivated by an example of
      prey evolution in a predator-prey system in which results show that only (non
      EUS) evolutionary repellor dynamics, where evolution is directed away from a
      singular strategy, or dynamics where the singular strategy is an evolutionary
      attractor, are possible. Moreover, the general theory can be used to show that
      these results are the only possibility for all Lotka-Volterra systems in which
      aside from the trade-offs all parameters are independent and in which the
      interaction terms are of quadratic order or less. The applicability of the theory
      is highlighted by examining the evolution of an intermediate predator in a tri
      trophic model.

PMID- 11825593
TI  - On the stability properties of a stochastic model for phage-bacteria interaction
      in open marine environment.
AB  - In this paper we extend the deterministic model for the epidemics induced by
      virulent phages on bacteria in marine environment introduced by Beretta and Kuang
      [Math. Biosci. 149 (1998) 57], allowing random fluctuations around the positive
      equilibrium. The stochastic stability properties of the model are investigated
      both analytically and numerically suggesting that the deterministic model is
      robust with respect to stochastic perturbations.

PMID- 11825592
TI  - Non-homogeneous infinite sites model under demographic change: mathematical
      description and asymptotic behavior of pairwise distributions.
AB  - We developed a mathematical model, which makes possible to predict joint
      distributions of numbers of mismatches in two or more linked regions of the
      genome, based on the Infinite Sites Models, under mutation-drift equilibrium as
      well as under various patterns of population growth. With mutation rates varying
      in the region, one of the predictions is different correlation between numbers of
      mismatches in the two regions, depending on the pattern of the past population
      growth (constant, slowly growing, or rapidly growing). Also, for slower growth
      patterns of population sizes, the coalescence tree is not necessarily 'starlike'.
      Thus, the joint distribution of mismatches, predicted by the model, provides
      additional insights into the demographic history of the populations. We also
      developed expectations and variances of sample statistics under different growth
      scenarios. As an application we used a sample of mitochondrial sequences from
      hypervariable regions 1 and 2 (HV1 and HV2), representing major world populations
      (Europeans, Asians and Africans). The patterns of joint distributions of numbers
      of mismatches differ markedly from one population to another. In addition, there
      is a considerable variability in the proportion of numbers of mismatches between
      HV1 and HV2 sequences. The patterns of bivariate distributions from the HV1 and
      HV2 data in these data are consistent with those generated by the model involving
      a stepwise change in population size.

PMID- 11825594
TI  - Isotype-specific antibody-secreting cells in systemic and mucosal associated
      lymphoid tissues and antibody responses in serum of conventional pigs inoculated
      with PEDV.
AB  - An enzyme-linked immunospot (ELISPOT) has been developed to detect porcine
      epidemic diarrhea virus (PEDV)-specific antibody secreting cells (ASC) in gut
      associated lymphoid tissues (duodenum and ileum lamina propria and mesenteric
      lymph nodes) and systemic locations (spleen and blood) of conventional pigs so as
      to characterise the mucosal and systemic antibody response generated by the
      infection with PEDV. A total number of 28 eleven-day-old conventional pigs were
      orally inoculated with the field isolate of the PEDV strain CV-777. Diarrhea was
      observed in 32% of the pigs and virus shedding was demonstrated in 100% between
      postinoculation day (PID) 1 and 8. Serum IgG and IgA antibodies to PEDV were
      detected by isotype ELISA from PID 12 and 15, respectively, reaching maximum
      values at PID 32 (IgG) and 21 (IgA). PEDV specific IgM ASC occurred in all the
      tissues between PID 4 and 7, with the strongest response in the intestinal lamina
      propria. IgA and IgG ASC responses were evident in the intestinal lymphoid
      tissues from PID 21, the highest number of specific ASC corresponded to the
      duodenum lamina propria. In the systemic lymphoid tissues the number of IgG and
      IgA ASC detected were lower than in the mucosal tissues, however, in the blood,
      presence of IgA ASC was constantly detected from PID 14 until the end of the
      experiment. Memory antibody response to the PEDV was also studied by secondary in
      vitro stimulation of the mononuclear cells (MNC) isolated from mesenteric lymph
      nodes, spleen and blood. The memory B cell response was prominent at PID 21 and
      25 and consisted in IgG and IgA ASC. To our knowledge, this is the first report
      to research into the presence and distribution of specific ASC in different
      locations of the systemic and the gut associated lymphoid tissues after a PEDV
      infection as well as the presence of memory B cells.

PMID- 11825595
TI  - Lack of effect of combining different stressors on innate immune responses of
      seabream (Sparus aurata L.).
AB  - A complex stressful event, which commonly occurs in modern aquacultural
      practices, was broken down into factors that were analysed both individually and
      jointly to assess their effect on two stress indicators (blood glucose and serum
      cortisol levels) and two activities of the innate immune response (serum
      complement and head-kidney leukocyte respiratory burst). For this, gilthead
      seabream (Sparus aurata L.) specimens were exposed to the following stressors:
      physical disturbance, crowding, anaesthesia with 2-phenoxyethanol and air
      exposure. At 0, 1, 2, 3 and 4 days post-stress, blood and serum samples were
      collected to measure glucose concentration and cortisol and complement levels,
      respectively. Head-kidney leukocytes were isolated and assayed to evaluate
      respiratory burst activity. The results show that physical disturbance, crowding
      and anaesthesia produced an occasional increase in glucose and cortisol
      concentrations. Crowding and anaesthesia induced a depression in complement
      activity, while hypoxia by air exposure caused a reduction in the respiratory
      burst. When all factors were jointly applied both humoral and cellular defences
      were compromised and cortisol values remained high throughout the experimental
      period. Any long-term effects of this abnormal serum cortisol levels on the
      immune system remain unknown.

PMID- 11825596
TI  - Analysis of the antigen-specific IFN-gamma producing T-cell subsets in cattle
      experimentally infected with Mycobacterium bovis.
AB  - Three 10 months old cattle were infected by the intratracheal route with 10(6)cfu
      of a field strain of Mycobacterium bovis. Blood samples were regularly collected
      for in vitro IFN-gamma production after antigenic stimulation. Peripheral blood
      cells of infected animals produced IFN-gamma in response to crude M. bovis
      antigens (live and heat-inactivated BCG and protein-purified derivative (PPD)) 3
      4 weeks after infection. The ratio of the response to bovine PPD versus avian PPD
      indicated a specific sensitisation for M. bovis antigens. Three months post
      infection (PI), animals were culled and M. bovis was cultured from tubercle
      lesions. At different time points, the frequency of specific M. bovis IFN-gamma
      producing CD4+, CD8+ and WC1+ T-cells in the peripheral blood was examined by
      flow cytometry. Two colour immunofluorescence staining of intracellular IFN-gamma
      and bovine cell surface molecules showed that both CD4+ and CD8+, but not WC1+, T
      cells produced IFN-gamma following stimulation with PPD, live or killed BCG. In
      two animals analysed, the relative percentage of circulating IFN-gamma producing
      CD8+ cells decreased between week 5 and week 9 PI. The same evolution was not
      observed for IFN-gamma secreting CD4+ cells. Magnetic positive selection of T
      cells from infected animals showed that CD4+ T-cells produced specific IFN-gamma
      only in the presence of antigen presenting cells (APCs). Positively selected CD8+
      T-cells secreted IFN-gamma only in the presence of recombinant human IL-2 and
      APCs. In vitro depletion of the CD4+ T-cells, but not the depletion of CD8+ or
      WC1+ T-cells, resulted in abrogation of the specific IFN-gamma production showing
      the key role of this cell population for the specific IFN-gamma production.

PMID- 11825597
TI  - Monocytes are required for optimum in vitro stimulation of bovine peripheral
      blood mononuclear cells by non-methylated CpG motifs.
AB  - Bacterial DNA and synthetic oligodeoxynucleotides (ODN) containing unmethylated
      CpG motifs within certain flanking base pairs are recognized as a danger signal
      by the innate immune system of vertebrates. Using lymphocyte proliferative
      response (LPR) and IFN-gamma secretion assays, a panel of 38 ODN was screened for
      immunostimulatory activity on bovine peripheral blood mononuclear cells. ODN
      composed of a nuclease resistant phosphorothioate backbone and a leading 5'
      TCGTCGTT-3' motif with two 5'-GTCGTT-3' motifs were highly stimulatory in both
      assays. Flow cytometric analysis and cell-specific surface marker labeling
      determined that B-cells (surface IgM(+)) were the primary cell population
      responding in the LPR assay. Depletion of T cells (CD3(+)) from the PBMC
      population did not affect IFN-gamma secretion or B-cell proliferation when
      cultured with CpG-ODN. However, depletion of monocytes (DH59B(+)) completely
      abrogated the ability of CpG-ODN to stimulate IFN-gamma secretion, and
      significantly reduced the B-cell proliferative response. These data establish the
      identity of an optimal immunostimulatory CpG motif for cattle and demonstrate
      that monocytes play a pivotal role in the ability of cell populations to respond
      to CpG-ODN. These data provide insight for future studies investigating the
      mechanism of CpG-ODN bioactivity and its application in novel vaccine
      formulations and immunotherapy.

PMID- 11825598
TI  - Determination of donor-type chimerism using a semi-quantitative PCR-based method
      in a canine model for bone marrow transplantation.
AB  - Dogs are used in preclinical transplantation models to study methods of
      allogeneic bone marrow transplantation (BMT). The evaluation of chimerism is of
      major significance for the investigation of graft-vs.-host (GvH) and host-vs.
      graft (HvG) reactions. To detect and quantitate male donor cells after a sex
      mismatched (male to female) allogeneic BMT, we established a semi-quantitative
      polymerase chain reaction (PCR) assay. Based on the canine Y-chromosome sex
      determining region (Sry) sequence, we designed primer specific for the detection
      of male DNA and optimised PCR conditions and cycle numbers. Artificial mixtures
      of male and female leukocytes were used to analyse the sensitivity of the assay.
      To validate our established method, we determined the percentage of chimerism in
      three transplanted female dogs. Under optimised conditions, the established PCR
      assay specifically detected male cells down to 0.01%, which corresponds to 0.1ng
      of transplanted male DNA. The percentage of chimerism could be quantitated either
      by agarose gel analysis or Southern blot analysis. Using our assay, we could
      confirm the percentage of chimerism in blood samples of three transplanted female
      canines, previously determined by karyotype analysis as 0, 100 and 100%,
      respectively. The established semi-quantitative PCR assay offers a quick, simple,
      accurate and sensitive way of evaluating and quantitating the percentage of
      chimerism in a sex-mismatched canine BMT model.

PMID- 11825599
TI  - Peanut and Amaranthus leucocarpus lectins discriminate between memory and
      naive/quiescent porcine lymphocytes.
AB  - Lectins are relevant tools to isolate and characterize different cellular sub
      populations. In this work, we used the lectins Arachis hypogaea (Peanut
      agglutinin, PNA) and Amaranthus leucocarpus (ALL), specific for Galss1, 3GalNAc,
      to characterize naive and memory lymphocytes from pigs, experimentally infected
      with the porcine rubulavirus (RvP). Our results showed that both lectins
      recognized preferentially lymphocytes with the CD4(+)CD8(+) phenotype (P<0.05).
      The phenotypic analysis of the cells recognized by these lectins indicated that
      PNA(+) lymphocytes showed higher rate of the CD29 antigen (PNA(+)CD29(high)) than
      ALL(+) (ALL(+)CD29(low)). The number of PNA(+)CD29(high) lymphocytes increased
      after 8 weeks of experimental infection with RvP, and most of the ALL(+)CD29(low)
      cells became CD29(middle). PNA(+) lymphocytes isolated from infected pigs
      proliferated after stimulation with the RvP, whereas ALL(+) cells did not. In
      vitro assays indicated that the ALL(+) cells from previously infected pigs
      diminished from 7.5 +/- 2 to 0.5 +/- 0.3% after RvP stimulation; whereas PNA(+)
      cells increased from 4 +/- 1 to 42 +/- 2%, whereas no modification in ALL(+) or
      PNA(+) cellular population was identified in lymphocytes from naive animals after
      RvP stimulation. Our results suggest that the cellular distribution/organization
      of the O-glycosydically linked glycans on lymphocytes may correlate with
      biological functions, and that PNA could be a tool to isolate specifically
      porcine memory T cell subsets, whereas ALL could be useful to isolate
      naive/quiescent T lymphocytes.

PMID- 11825600
TI  - Recombinant equine interferons: expression cloning and biological activity.
AB  - Interferons (IFNs) are important mediators of the immune system. Their antiviral
      activity is an integral part of the innate immune defence, but all IFNs have
      immune regulatory functions also. Besides rec.eq.IFN-beta detailed descriptions
      on other rec.IFNs were lacking and none of the proteins was available. To compare
      the equine IFNs and allow detailed studies on proteins and bioactivity, we
      performed the expression cloning of rec.eq.IFN-alpha, -beta and -gamma. To
      achieve maximal expression, a bacterial expression system was chosen.
      Additionally, rec.eq.IFN-beta and -gamma were expressed in mouse B-cells. The
      antiviral activity was characterised using different cell lines and equine
      viruses. The results demonstrate a broad antiviral activity of rec.eq.IFN-alpha
      being active against all viruses tested, including the equine herpesviruses EHV-1
      and -4, while rec.eq.IFN-beta was only active using primary horse cells.
      Protection depended on viruses, cell lines, infectious doses, amount and time of
      IFN action prior to infection. While rec.eq.IFN-gamma did not act antivirally, it
      was effective as an immune modulator of monocytes in vitro. The implications of
      our findings on clinical immunology and virology, including therapeutic
      applications of equine IFNs will be discussed.

PMID- 11825601
TI  - Effect of experimental infection of cattle with bovine herpesvirus-1 (BHV-1) on
      the ex vivo interaction of bovine leukocytes with Mannheimia (Pasteurella)
      haemolytica leukotoxin.
AB  - Mannheimia (Pasteurella) haemolytica A1 produces an extracellular leukotoxin
      (LKT) that is reported to bind the beta(2)-integrin CD11a/CD18 (LEA-1) on
      ruminant leukocytes. LKT binding induces activation, and subsequent cytolysis, of
      these cells. It is well known that active viral infection greatly increases the
      susceptibility of cattle to pasteurellosis. To better understand the mechanism by
      which this occurs, we investigated the effects of experimental in vivo infection
      of cattle with bovine herpes virus-1 (BHV-1) on the ex vivo interaction of bovine
      leukocytes with the M. haemolytica LKT. In this study, we demonstrated that
      active BHV-1 infection increased the expression of the beta(2)-integrin
      CD11a/CD18 (as defined by the mAb BAT75) on bovine peripheral blood neutrophils,
      enhanced the binding of LKT to bronchoalveolar lavage (BAL) leukocytes and
      peripheral blood neutrophils, and increased the killing of BAL leukocytes and
      peripheral blood leukocytes by LKT. In addition, BHV-1 greatly increased the
      number of BAL, resulting in many more LKT-responsive cells being present in the
      lungs. These findings might explain in part the increased susceptibility of BHV-1
      infected cattle to pneumonic pasteurellosis.

PMID- 11825602
TI  - T-cell populations responsive to bovine respiratory syncytial virus in
      seronegative calves.
AB  - Calves lacking detectable serum antibodies against bovine respiratory syncytial
      virus (BRSV) were screened for virus-specific T-cell memory. Peripheral blood
      mononuclear cells were cultured in vitro with live BRSV and analyzed by dual
      color flow cytometry for surface expression of CD25 on CD4(+), CD8(+), and
      gammadeltaT-cells. Significant recall responses were detected in some of the
      seronegative calves. Modified live BRSV vaccine was administered to these and to
      a group of non-responding calves. Following vaccination, virus-specific IgG,
      virus neutralizing antibody, and T-cell recall responses were all elevated more
      rapidly in the group with BRSV-sensitive T-cells than in the T-cell-negative
      group, which suggested that calves in the first group were previously exposed to
      BRSV. This demonstrates that exposure to BRSV can induce T and B cell memory in
      young calves without causing seroconversion. The calves were presumably exposed
      to BRSV while they had maternal antibody, which inhibited the calves from
      developing an antibody response.

PMID- 11825603
TI  - Human stefin B readily forms amyloid fibrils in vitro.
AB  - Human stefin B (cystatin B) is an intracellular cysteine proteinase inhibitor
      broadly distributed in different tissues. Here, we show that recombinant human
      stefin B readily forms amyloid fibrils in vitro. It dimerises and further
      oligomerises, starting from the native-like acid intermediate, I(N), populated at
      pH 5. On standing at room temperature it produces regular (over 4 microm long)
      fibrils over a period of several months. These have been visualised by
      transmission electron microscopy and atomic force microscopy. Their cross
      sectional diameter is about 14 nm and blocks of 27 nm repeat longitudinally. The
      fibrils are smooth, of unbranched surface, consistent with findings of other
      amyloid fibrils. Thioflavin T fluorescence spectra as a function of time were
      recorded and Congo red dye binding to the fibrils was demonstrated. Adding 10%
      (v/v) trifluoroethanol resulted in an increased rate of fibrillation with a
      typical lag phase. The finding that human stefin B, in contrast to the homologue
      stefin A, forms amyloid fibrils rather easily should promote further studies of
      the protein's behaviour in vivo, and/or as a model system for fibrillogenesis.

PMID- 11825604
TI  - Purification, kinetic studies, and homology model of Escherichia coli fructose
      1,6-bisphosphatase.
AB  - Previous kinetic characterization of Escherichia coli fructose 1,6-bisphosphatase
      (FBPase) was performed on enzyme with an estimated purity of only 50%.
      Contradictory kinetic properties of the partially purified E. coli FBPase have
      been reported in regard to AMP cooperativity and inactivation by fructose-2,6
      bisphosphate. In this investigation, a new purification for E. coli FBPase has
      been devised yielding enzyme with purity levels as high as 98%. This highly
      purified E. coli FBPase was characterized and the data compared to that for the
      pig kidney enzyme. Also, a homology model was created based upon the known three
      dimensional structure of the pig kidney enzyme. The kcat of the E. coli FBPase
      was 14.6 s(-1) as compared to 21 s(-1) for the pig kidney enzyme, while the K(m)
      of the E. coli enzyme was approximately 10-fold higher than that of the pig
      kidney enzyme. The concentration of Mg2+ required to bring E. coli FBPase to half
      maximal activity was estimated to be 0.62 mM Mg2+, which is twice that required
      for the pig kidney enzyme. Unlike the pig kidney enzyme, the Mg2+ activation of
      the E. coli FBPase is not cooperative. AMP inhibition of mammalian FBPases is
      cooperative with a Hill coefficient of 2; however, the E. coli FBPase displays no
      cooperativity. Although cooperativity is not observed, the E. coli and pig kidney
      enzymes show similar AMP affinity. The quaternary structure of the E. coli enzyme
      is tetrameric, although higher molecular mass aggregates were also observed. The
      homology model of the E. coli enzyme indicated slight variations in the ligand
      binding pockets compared to the pig kidney enzyme. The homology model of the E.
      coli enzyme also identified significant changes in the interfaces between the
      subunits, indicating possible changes in the path of communication of the
      allosteric signal.

PMID- 11825605
TI  - Temperature-dependent binding of monoclonal antibodies to C hordein.
AB  - The consensus octapeptide repeat motif of the barley seed storage protein C
      hordein, Pro-Gln-Gln-Pro-Phe-Pro-Gln-Gln, forms the epitope of two anti-prolamin
      monoclonal antibodies (Mabs), IFRN 0061 and 0614. The Mabs were found to exhibit
      unusual temperature-dependent binding characteristics, recognising C hordein and
      a peptide corresponding to the consensus repeat at 5 degrees C but not at 37
      degrees C, as determined by enzyme-linked immunosorbent assay (ELISA). The K(d)
      of IFRN 0614 for the consensus peptide was found to be 1.2x10(12) mol(-1) at 12
      degrees C, but no constant could be calculated at 37 degrees C due to a lack of
      binding. Similar ELISA binding characteristics were observed with an anti-C
      hordein polyclonal antiserum and a Mab raised to the consensus peptide. Circular
      dichroism (CD) and Fourier-transform infrared (FTIR) spectroscopy showed that the
      protein and the consensus peptide exist in a temperature-dependent equilibrium of
      poly-L-proline II type structures and beta-turn conformations. Whilst
      thermodynamic and kinetic effects may reduce antibody binding at higher
      temperatures, they cannot account for the complete loss of Mab recognition at
      higher temperatures. It seems likely that the Mabs preferentially recognise the
      Pro-Gln-Gln-Pro-Phe-Pro-Gln-Gln motif when presented in a conformation which may
      correspond to the poly-L-proline II type conformation which dominates the CD and
      FTIR spectra at 4-12 degrees C.

PMID- 11825606
TI  - A mutational analysis of the active site of human type II inosine 5'
      monophosphate dehydrogenase.
AB  - The oxidation of IMP to XMP is the rate-limiting step in the de novo synthesis of
      guanine ribonucleotides. This NAD-dependent reaction is catalyzed by the enzyme
      inosine monophosphate dehydrogenase (IMPDH). Based upon the recent structural
      determination of IMPDH complexed to oxidized IMP (XMP*) and the potent
      uncompetitive inhibitor mycophenolic acid (MPA), we have selected active site
      residues and prepared mutants of human type II IMPDH. The catalytic parameters of
      these mutants were determined. Mutations G326A, D364A, and the active site
      nucleophile C331A all abolish enzyme activity to less than 0.1% of wild type.
      These residues line the IMP binding pocket and are necessary for correct
      positioning of the substrate, Asp364 serving to anchor the ribose ring of the
      nucleotide. In the MPA/NAD binding site, significant loss of activity was seen by
      mutation of any residue of the triad Arg322, Asn303, Asp274 which form a hydrogen
      bonding network lining one side of this pocket. From a model of NAD bound to the
      active site consistent with the mutational data, we propose that these resides
      are important in binding the ribose ring of the nicotinamide substrate.
      Additionally, mutations in the pair Thr333, Gln441, which lies close to the
      xanthine ring, cause a significant drop in the catalytic activity of IMPDH. It is
      proposed that these residues serve to deliver the catalytic water molecule
      required for hydrolysis of the cysteine-bound XMP* intermediate formed after
      oxidation by NAD.

PMID- 11825607
TI  - The novel non-glycosylated invertase from Candida utilis (the properties and the
      conditions of production and purification).
AB  - The Candida utilis yeast, which is cultivated in liquid media enriched with
      saccharose, synthesizes the well-known invertase of 300 kDa (EC 3.2.1.26). This
      enzyme is present both intracellularly in the periplasmic space and
      extracellularly in the culture broth. However, it was determined that the same C.
      utilis strain cultured in certain conditions is simultaneously capable of
      producing another, still unknown form of invertase with a molecular mass of 60
      kDa. The presence of the latter enzymatic form was detected in cells as well as
      in the liquid culture medium. Both invertase forms were purified using a three
      step process (ion-exchange chromatography, affinity chromatography, and
      preparative column electrophoresis) and named, due to their different migration
      ratio in polyacrylamide gel electrophoresis, F-form (Fast; 60 kDa) and S-form
      (Slow; 300 kDa). The F-form of invertase was found to be nonglycosylated as
      opposed to the well-known S-form of invertase from the same source. The
      physicochemical properties of the F-form of invertase (isoelectric point,
      substrate specificity, pH, and temperature optima) were determined and compared
      with those of the S-form of the enzyme.

PMID- 11825608
TI  - Structural characterization of bacteriophage M13 solubilization by amphiphiles.
AB  - The structural properties of bacteriophage M13 during disassembly were studied in
      different membrane model systems, composed of a homologue series of the
      detergents sodium octyl sulfate, sodium decyl sulfate, and sodium dodecyl
      sulfate. The structural changes during phage disruption were monitored by spin
      labeled electron spin resonance (ESR) and circular dichroism spectroscopy. For
      the purpose of ESR spectroscopy the major coat protein mutants V31C and G38C were
      site-directed spin labeled in the intact phage particle. These mutants were
      selected because the mutated sites are located in the hydrophobic part of the
      protein, and provide good reporting locations for phage integrity. All
      amphiphiles studied were capable of phage disruption. However, no significant
      phage disruption was detected below the critical micelle concentration of the
      amphiphile used. Based on this finding and the linear dependence of phage
      disruption by amphiphiles on the phage concentration, it is suggested that the
      solubilization of the proteins of the phage coat by amphiphiles starts with an
      attachment to and penetration of amphiphile molecules into the phage particle.
      The amphiphile concentration in the phage increases in proportion to the
      amphiphile concentration in the aqueous phase. Incorporation of the amphiphile in
      the phage particle is accompanied with a change in local mobility of the spin
      labeled part of the coat protein and its secondary structure. With increasing the
      amphiphile concentration in the phage particle, a concentration is reached where
      the concentration of the amphiphile in the aqueous phase is around its critical
      micelle concentration. A further increase in amphiphile concentration results in
      massive phage disruption. Phage disruption by amphiphiles appears to be dependent
      on the phage coat mutations. It is concluded that phage disruption is dependent
      on a hydrophobic effect, since phage solubilization could significantly be
      increased by keeping the hydrophilic part of the amphiphile constant, while
      increasing its hydrophobic part.

PMID- 11825609
TI  - Insight into the activation mechanism of Escherichia coli octaprenyl
      pyrophosphate synthase derived from pre-steady-state kinetic analysis.
AB  - Octaprenyl pyrophosphate synthase (OPPs) catalyzes the sequential condensation of
      five molecules of isopentenyl pyrophosphate with farnesyl pyrophosphate to
      generate all-trans C40-octaprenyl pyrophosphate, which constitutes the side chain
      of ubiquinone. Due to the slow product release, a long-chain polyprenyl
      pyrophosphate synthase often requires detergent or another factor for optimal
      activity. Our previous studies in examining the activity enhancement of
      Escherichia coli undecaprenyl pyrophosphate synthase have demonstrated a switch
      of the rate-determining step from product release to isopentenyl pyrophosphate
      (IPP) condensation reaction in the presence of Triton [12]. In order to
      understand the mechanism of enzyme activation for E. coli OPPs, a single-turnover
      reaction was performed and the measured IPP condensation rate (2 s(-1)) was 100
      times larger than the steady-state rate (0.02 s(-1)). The high molecular weight
      fractions and Triton could accelerate the steady-state rate by 3-fold (0.06 s(
      1)) but insufficient to cause full activation (100-fold). A burst product
      formation was observed in enzyme multiple turnovers indicating a slow product
      release.

PMID- 11825610
TI  - A site-directed mutagenesis analysis of tNOX functional domains.
AB  - Constitutive NADH oxidase proteins of the mammalian cell surface exhibit two
      different activities, oxidation of hydroquinones (or NADH) and protein disulfide
      thiol interchange which alternate to yield oscillatory patterns with period
      lengths of 24 min. A drug-responsive tNOX (tumor-associated NADH oxidase) has a
      period length of about 22 min. The tNOX cDNA has been cloned and expressed. These
      two proteins are representative of cycling oxidase proteins of the plant and
      animal cell surface. In this report, we describe a series of eight amino acid
      replacements in tNOX which, when expressed in Escherichia coli, were analyzed for
      enzymatic activity, drug response and period length. Replacement sites selected
      include six cysteines that lie within the processed plasma membrane (34 kDa) form
      of the protein, and amino acids located in putative drug and adenine nucleotide
      (NADH) binding domains. The latter, plus two of the cysteine replacements,
      resulted in a loss of enzymatic activity. The recombinant tNOX with the modified
      drug binding site retained activity but the activity was no longer drug
      responsive. The four remaining cysteine replacements were of interest in that
      both activity and drug response were retained but the period length for both NADH
      oxidation and protein disulfide-thiol interchange was increased from 22 min to 36
      or 42 min. The findings confirm the correctness of the drug and adenine
      nucleotide binding motifs within the tNOX protein and imply a potential critical
      role of cysteine residues in determining the period length.

PMID- 11825611
TI  - Interaction of bovine (BSA) and human (HSA) serum albumins with ionic
      surfactants: spectroscopy and modelling.
AB  - The binding of several different categories of small molecules to bovine (BSA)
      and human (HSA) serum albumins has been studied for many years through different
      spectroscopic techniques to elucidate details of the protein structure and
      binding mechanism. In this work we present the results of the study of the
      interactions of BSA and HSA with the anionic sodium dodecyl sulfate (SDS),
      cationic cethyltrimethylammonium chloride (CTAC) and zwitterionic N-hexadecyl-N,N
      dimethyl-3-ammonium-1-propanesulfonate (HPS) monitored by fluorescence
      spectroscopy of the intrinsic tryptophans at pH 5.0. Similarly to pH 7.0 and 9.0,
      at low concentrations, the interaction of BSA with these surfactants shows a
      quenching of fluorescence with Stern-Volmer quenching constants of (1.1+/
      0.1)x10(4) M(-1), (3.2+/-0.1)x10(3) M(-1) and (2.1+/-0.1)x10(3) M(-1) for SDS,
      HPS and CTAC, respectively, which are associated to the 'effective' association
      constants to the protein. On the interaction of these surfactants with HSA, an
      opposite effect was observed as compared to BSA, i.e., an enhancement of
      fluorescence takes place. For both proteins, at low surfactant concentrations, a
      positive cooperativity was observed and the Hill plot model was used to estimate
      the number of surfactant binding sites, as well as the association constants of
      the surfactants to the proteins. It is worthy of notice that the binding
      constants for the surfactants at pH 5.0 are lower as compared to pH 7.0 and 9.0.
      This is probably due to fact that the protein at this acid pH is quite compact
      reducing the accessibility of the surfactants to the hydrophobic cavities in the
      binding sites. The interaction of myristic acid with both proteins shows a
      similar fluorescence behaviour, suggesting that the mechanism of the interaction
      is the same. Recently published crystallographic studies of HSA-myristate complex
      were used to perform a modelling study with the aim to explain the fluorescence
      results. The crystallographic structure reveals that a total of five myristic
      acid molecules are asymmetrically bound in the macromolecule. Three of these
      sites correspond to higher affinity ones and correlate with high association
      constants described in the literature. Our models for BSA and HSA with bound SDS
      suggest that the surfactant could be bound at the same sites as those reported in
      the crystal structure for the fatty acid. The differences in tryptophan vicinity
      upon surfactant binding are explored in the models in order to explain the
      observed spectroscopic changes. For BSA the quenching is due to a direct contact
      of a surfactant molecule with the indole of W131 residue. It is clear that the
      binding site in BSA which is very close, in contact with tryptophan W131,
      corresponds to a lower affinity site, explaining the lower binding constants
      obtained from fluorescence studies. In the case of HSA the enhancement of
      fluorescence is due to the removal of static quenching of W214 residue in the
      intact protein caused by nearby residues in the vicinity of this tryptophan.

PMID- 11825612
TI  - Identification of histidine residues at the active site of Megalobatrachus
      japonicus alkaline phosphatase by chemical modification.
AB  - Alkaline phosphatase from Megalobatrachus japonicus was inactivated by diethyl
      pyrocarbonate (DEP). The inactivation followed pseudo-first-order kinetics with a
      second-order rate constant of 176 M(-1) x min(-1) at pH 6.2 and 25 degrees C. The
      loss of enzyme activity was accompanied with an increase in absorbance at 242 nm
      and the inactivated enzyme was re-activated by hydroxylamine, indicating the
      modification of histidine residues. This conclusion was also confirmed by the pH
      profiles of inactivation, which showed the involvement of a residue with pK(a) of
      6.6. The presence of glycerol 3-phosphate, AMP and phosphate protected the enzyme
      against inactivation. The results revealed that the histidine residues modified
      by DEP were located at the active site. Spectrophotometric quantification of
      modified residues showed that modification of two histidine residues per active
      site led to complete inactivation, but kinetic stoichiometry indicated that one
      molecule of modifier reacted with one active site during inactivation, probably
      suggesting that two essential histidine residues per active site are necessary
      for complete activity whereas modification of a single histidine residue per
      active site is enough to result in inactivation.

PMID- 11825613
TI  - Purification, crystallisation and X-ray diffraction study of fully functional
      laccases from two ligninolytic fungi.
AB  - Laccase isozymes from the white-rot basidiomycete fungi Trametes versicolor and
      Pycnoporus cinnabarinus were purified to apparent iso-electric homogeneity and
      crystallised. T. versicolor laccase crystallises in two crystal forms, both with
      the orthorhombic space group P2(1)2(1)2(1), which diffract to 1.9 and 2.95 A
      resolution, respectively. The crystals of P. cinnabarinus laccase belong to the
      monoclinic space group C2 and diffract to at least 2.2 A resolution. All the
      laccase crystals are suitable for X-ray structure determination and contain a
      full complement of copper ions.

PMID- 11825614
TI  - Analysis by systematic deletion of amino acids of the action of the ribotoxin
      restrictocin.
AB  - A series of contiguous deletions were made in a cDNA encoding the ribonuclease
      restrictocin with the purpose of identifying the amino acids that are essential
      for the cleavage of the phosphodiester bond on the 3' side of G4325 in the alpha
      sarcin/ricin domain of mammalian (rat) 28S rRNA. In all 93 of 149 amino acids,
      62% of the residues in restrictocin, were not essential for the action of the
      toxin. Of the five residues that have been proposed to constitute the active
      site, three could be deleted without loss of activity if they were part of a
      deletion of three or five amino acids but not if they were removed singly. It is
      likely that the loss of these three residues is compensated for by a neighboring
      residue that occupies the structural space created by the larger amino acid
      deletions. This was demonstrated to be the case for the active site residue Glu95
      which in the deletion mutant Delta91-95 is replaced by Asp90. Systematic deletion
      of amino acids is a rapid, cost effective method for identifying the residues in
      a protein likely to contribute directly to function and, hence, deserving of
      closer scrutiny. Moreover, a semiquantitative estimate of the contribution of the
      residue to function can be made. For this reason the method may be useful for
      functional proteomics.

PMID- 11825615
TI  - Cloning, expression and characterisation of a human Nudix hydrolase specific for
      adenosine 5'-diphosphoribose (ADP-ribose).
AB  - The human NUDT9 gene has been mapped to 4q22 and shown to give rise to two
      alternatively spliced mRNAs, NUDT9alpha and NUDT9beta, that encode a member of
      the Nudix hydrolase family. Both transcripts were readily detected in heart and
      skeletal muscle and also in liver, kidney and pancreas. NUDT9alpha protein was
      expressed in Escherichia coli and shown specifically to hydrolyse ADP-ribose and
      IDP-ribose to the corresponding nucleoside 5'-monophosphates and ribose 5
      phosphate. No other nucleotide substrates were hydrolysed significantly.
      NUDT9alpha was inhibited by fluoride and by N-acetyl-p-benzoquinoneimine and had
      K(m) and kcat values of 180 microM and 8 s(-1) respectively with ADP-ribose as
      substrate. The full-length 39.1 kDa NUDT9alpha has a potential mitochondrial
      leader sequence, which would give rise to a mature 34.2 kDa mitochondrial
      protein. Apart from the high K(m) value, the properties of NUDT9alpha are close
      to those of the known mammalian 40 kDa cytoplasmic ADPRibase-1 and 35 kDa
      mitochondrial ADPRibase-m. However, any relationship between the NUDT9 species
      and the previously reported ADPRibases remains to be established.

PMID- 11825616
TI  - Site-directed mutagenesis of the essential arginine of the formate dehydrogenase
      active centre.
AB  - Sequence alignment shows that residue Arg 284 (according to the numbering of the
      residues in formate dehydrogenase, FDH, from the methylotrophic bacterium
      Pseudomonas sp. 101) is conserved in NAD-dependent FDHs and D-specific 2
      hydroxyacid dehydrogenases. Mutation of Arg 284 to glutamine and alanine results
      in a change of the catalytic, thermodynamic and spectral properties of FDH. In
      comparison to wild-type, the affinity of the mutants for the substrate
      (K(formate)m) or the transition state analogue (K(azide)i) decreases and
      correlates with the ability of the side chain of residue 284 to form H-bonds. In
      contrast, the affinity for the coenzyme (K(NAD)d or K(NAD)m) is either not
      affected or increases and correlates inversely with the partial positive charge
      of the side chain. The temperature dependence of circular dichroism (CD) spectra
      of the wild-type FDH and its Ala mutant has been studied over the 5-90 degrees C
      temperature range. Both proteins reveal regions of enhanced conformational
      mobility at the predenaturing temperatures (40-55 degrees C) associated with a
      change of enzyme kinetic parameters and a co-operative transition around 55-70
      degrees C which is followed by the loss of enzyme activity. CD spectra of the
      wild-type and mutant proteins were deconvoluted and contributions from various
      types of secondary structure estimated. It is shown that the co-operative
      transition at 55-70 degrees C in the FDH protein globule is triggered by a loss
      of alpha-helical secondary structure. The results confirm the conclusion, from
      the crystal structures, that Arg 284 is directly involved in substrate binding.
      In addition this residue seems to exert a major structural role by supporting the
      catalytic conformation of the enzyme active centre.

PMID- 11825617
TI  - Water sorption isotherms and enthalpies of water sorption by lysozyme using the
      quartz crystal microbalance/heat conduction calorimeter.
AB  - The water sorption isotherm and the water vapor activity dependence of the
      enthalpy of water sorption Delta(sorp)Hdegrees of lysozyme have been measured at
      25 degrees C. A thin film of lysozyme of mass 250 microg was exposed to H2O/N2
      mixtures in a quartz crystal microbalance/heat conduction calorimeter (QCM/HCC).
      The QCM/HCC is a new gravimetric/calorimetric method that measures simultaneously
      and with high precision the mass change and the corresponding heat flow in a thin
      film exposed to a gas. Delta(sorp)Hdegrees for lysozyme agrees with previous
      determinations, although hysteresis effects are evident in the data. No van't
      Hoff analysis is necessary because sorption enthalpies are measured
      calorimetrically. The water vapor activity dependence of Delta(sorp)Hdegrees
      agrees with that measured previously by Bone. As the water content of the
      lysozyme film drops below 10 mass%, Delta(sorp)Hdegrees becomes more exothermic,
      indicating that water is being bound to the charged or highly polar groups of the
      solvent-accessible surface of lysozyme. The dynamics of water uptake and release
      from lysozyme thin films are much slower than in polymer films of comparable
      thickness. Because the QCM/HCC operates with sub-milligram samples, any protein
      is now amenable to study by this technique.

PMID- 11825618
TI  - Chorismate lyase: kinetics and engineering for stability.
AB  - By removing the enolpyruvyl group from chorismate, chorismate lyase (CL) produces
      p-hydroxybenzoate (p-HB) for the ubiquinone biosynthetic pathway. We have
      analyzed CL by several spectroscopic and chemical techniques and measured its
      kinetic (kcat=1.7 s(-1), K(m)=29 microM) and product inhibition parameters
      (K(p)=2.1 microM for p-HB). Protein aggregation, a serious problem with wild type
      CL, proved to be primarily due to the presence of two surface-active cysteines,
      whose chemical modification or mutation (to serines) gave greatly improved
      solution behavior and minor effects on enzyme activity. CL is strongly inhibited
      by its product p-HB; for this reason activity and inhibition measurements were
      analyzed by both initial rate and progress curve methods. The results are
      consistent, but in this case where the stable enzyme-product complex rapidly
      becomes the predominant form of the enzyme, progress curve methods are more
      efficient. We also report inhibition measurements with several substrate and
      product analogs that give information on ligand binding interactions of the
      active site. The biological function of the unusual product retention remains
      uncertain, but may involve a mechanism of directed delivery to the membrane-bound
      enzyme that follows CL in the ubiquinone pathway.

PMID- 11825619
TI  - Native-like secondary structure of molten globules.
AB  - The most common evidence for the existence of secondary structure in a globular
      protein is the presence of a strongly pronounced far-UV circular dichroism (CD)
      spectrum. Although CD spectra of native proteins are well described and their
      quantitative analysis is widely used, similar studies for denatured proteins have
      still to be done. Far-UV CD spectra of nine proteins in the native and the pH
      induced molten globule states were acquired and analyzed. Singular value
      decomposition showed that the spectra of molten globules could be described as a
      superposition of at least three independent components (most likely alpha-, beta-
      and irregular structure). A self-consistent procedure of CD spectra analysis
      revealed the existence of a clear correlation between the shape of the molten
      globule spectra and the content of secondary structure elements in the
      corresponding native proteins, as determined from X-ray data. A mathematical
      expression of this correlation in terms of the Pierson coefficient amounts to the
      value of 0.9 for both the alpha-helix and the beta-structure. Thus, the secondary
      structure of proteins in the molten globule state is close to that in the native
      state.

PMID- 11825620
TI  - Molecular characterization of the poly(3-hydroxybutyrate) (PHB) synthase from
      Ralstonia eutropha: in vitro evolution, site-specific mutagenesis and development
      of a PHB synthase protein model.
AB  - A threading model of the Ralstonia eutropha polyhydroxyalkanoate (PHA) synthase
      was developed based on the homology to the Burkholderia glumae lipase, whose
      structure has been resolved by X-ray analysis. The lid-like structure in the
      model was discussed. In this study, various R. eutropha PHA synthase mutants were
      generated employing random as well as site-specific mutagenesis. Four permissive
      mutants (double and triple mutations) were obtained from single gene shuffling,
      which showed reduced activity and whose mutation sites mapped at variable surface
      exposed positions. Six site-specific mutations were generated in order to
      identify amino acid residues which might be involved in substrate specificity.
      Replacement of residues T323 (I/S) and C438 (G), respectively, which are located
      in the core structure of the PHA synthase model, abolished PHA synthase activity.
      Replacement of the two amino acid residues Y445 (F) and L446 (K), respectively,
      which are located at the surface of the protein model and adjacent to W425,
      resulted in reduced activity without changing substrate specificity and
      indicating a functional role of these residues. The E267K mutant exhibited only
      slightly reduced activity with a surface-exposed mutation site. Four site
      specific deletions were generated to evaluate the role of the C-terminus and
      variant amino acid sequence regions, which link highly conserved regions. Deleted
      regions were D281-D290, A372-C382, E578-A589 and V585-A589 and the respective PHA
      synthases showed no detectable activity, indicating an essential role of the
      variable C-terminus and the linking regions between conserved blocks 2 and 3 as
      well as 3 and 4. Moreover, the N-terminal part of the class II PHA synthase
      (PhaC(Pa)) from Pseudomonas aeruginosa and the C-terminal part of the class I PHA
      synthase (PhaC(Re)) from R. eutropha were fused, respectively, resulting in three
      fusion proteins with no detectable in vivo activity. However, the fusion protein
      F1 (PhaC(Pa)-1-265-PhaC(Re)-289-589) showed 13% of wild type in vitro activity
      with the fusion point located at a surface-exposed loop region.

PMID- 11825621
TI  - Mutational analysis of sites in sepiapterin reductase phosphorylated by
      Ca2+/calmodulin-dependent protein kinase II.
AB  - Sepiapterin reductase (SPR) catalyzes the last step in the pathway of
      tetrahydrobiopterin biosynthesis in tissues. SPR is phosphorylated by Ca2+
      dependent protein kinases, which indicates that Ca2+-activated protein kinases
      may play a role in the regulation of SPR in vivo. Phosphorylation sites of rat
      sepiapterin reductase (rSPR) by Ca2+/calmodulin-dependent protein kinase II were
      determined in the present study. Using specific monoclonal anti-phospho-Ser and 
      Thr antibodies, we found that only Ser residues of rSPR were phosphorylated. We
      constructed several point mutants of SPR by systematically replacing the three
      Ser residues by Ala ones. These mutants showed that all three Ser residues, i.e.
      S46, S196, and S214, of rSPR were phosphorylated. We also recognized that only
      Ser-213 of human SPR was phosphorylated. Each of these serine residues in SPR was
      found in the consensus sequence (Arg-X-X-Ser/Thr) of the phosphorylation site.

PMID- 11825622
TI  - Structure of the major glycolipid from Rothia dentocariosa.
AB  - Structural studies of the major glycolipid isolated from Rothia dentocariosa were
      carried out by specific chemical degradation and nuclear magnetic resonance
      spectroscopy. The glycolipid was found to be a dimannosylacylmonoglyceride in
      which the carbohydrate part was the glycerol-linked dimannoside alpha-D-Manp-(1-
      >3)-alpha-D-Manp-(1-->3)-sn-Gro, and the internal mannose was esterified at C-6
      by fatty acid residue. The other fatty acyl chain substituted the primary
      methylene position of glycerol. The occurrence of this glycolipid is limited to
      the related microorganisms. The structural characteristics can facilitate the
      differentiation of some genera.

PMID- 11825623
TI  - Stability of cytadherence-related proteins P140/P110 in Mycoplasma genitalium
      requires MG218 and unidentified factors.
AB  - BACKGROUND: Tip-mediated cytadherence in Mycoplasma genitalium requires the
      structural and functional stability of the P140 adhesin, its operon-related
      protein P110, and the high molecular weight protein MG218 (190-kDa). Disruption
      mutants of mg218 unable to express MG218 exhibit both a non-cytadhering phenotype
      and P140/P110 instability, while disruption mutants that synthesize a truncated
      MG218 (160 kDa) retain the stability of P140/P110 and are >95% cytadhering.
      However, the origin of the MG218 truncated protein in these mutants is unclear.
      Therefore, we attempted to identify the origin of the truncated MG218 protein and
      to evaluate whether this truncated protein possessed the C-terminal part of
      MG218. In addition, we used spontaneous mutants lacking P140 to assess the role
      of MG218 in the stability of P140/P110. METHODS: RNA from M. genitalium mutant
      producing truncated MG218 was subjected to primer extension analysis to identify
      the origin of expression of truncated MG218. Extracts of this mutant were
      examined for the presence of the C-terminal region of MG218 by immunoblot. In
      addition, pulse-chase analysis was performed to assess the role of MG218 in the
      stability of P140/P110 in spontaneous p140 mutants. RESULTS: Primer extension
      analysis identified a transcriptional start point adjacent to the gentamycin
      resistance gene in disrupted mg218 mutants. Antibodies directed against the C
      terminal region (amino acids 1651-1666) of MG218 bound to truncated MG218 protein
      from mutants. Spontaneous p140 mutants subjected to pulse chase analysis
      indicated that solely class I mutants exhibited instability of P140/P110 in the
      presence of intact MG218. CONCLUSIONS: Expression of truncated MG218 in M.
      genitalium mg218 mutants appears to be due to the presence of a putative promoter
      upstream to the point of mg218 disruption; this truncated protein possesses the C
      terminal region of MG218. However, pulse chase results from spontaneously
      arising, non-cytadhering P140-deficient M. genitalium mutants suggest that the
      stability of P140 and P110 requires not only MG218 but also additional factors.

PMID- 11825624
TI  - Neuroprotective effects of progesterone on damage elicited by acute global
      cerebral ischemia in neurons of the caudate nucleus.
AB  - BACKGROUND: In addition to the hippocampus, the dorsolateral caudate nucleus (CN)
      and the pars reticularis of the substantia nigra (SNr) are among the most
      vulnerable brain areas to ischemia. A possible association of the neuronal injury
      in these two subcortical nuclei has been proposed, the primary damage affecting
      the CN GABAergic neurons innervating the SNr, and secondarily the SNr neurons as
      a result of an imbalance of GABAergic and glutamatergic input to the SNr.
      Progesterone (P(4)) exerts a GABAergic action on the central nervous system (CNS)
      and is known to protect neurons in the cat hippocampus from the damaging effect
      of acute global cerebral ischemia (AGCI). The effects of AGCI on the neuronal
      populations of the CN and SNr, in addition to the possible neuroprotective
      effects of P(4), were assessed in cats in the present study. METHODS:
      Ovariectomized adult cats were treated subcutaneously (s.c.) with either P(4) (10
      mg/kg/day) or corn oil during the 7 days before and 7 days after being subjected
      to a period of AGCI by 15 min of cardiorespiratory arrest followed by 4 min of
      reanimation. After 14 days of survival, animals were sacrificed and their brains
      perfused in situ with phosphate-buffered 10% formaldehyde for histologic
      examination. RESULTS: ACGI resulted in an intense glial reaction in the CN and a
      significant loss (43%) of medium-sized neurons of the CN, but no difference was
      found in the densities of SNr neurons between controls and ischemic oil- and P(4)
      treated cats. Progesterone treatment completely prevented CN neuronal loss.
      CONCLUSIONS: The overall results point to the higher vulnerability of CN neurons
      to ischemia as compared to neurons in the SNr and show the protective effects of
      P(4) upon CN neuronal damage after ischemia.

PMID- 11825625
TI  - Effect of nutritional status and ozone exposure on rat brain serotonin.
AB  - BACKGROUND: Ozone is an environmental pollutant that has widely documented
      deleterious effects on exposed organisms. In Mexico City, this pollutant
      frequently reaches concentrations that surpass safe health limits. In addition,
      it has been reported that the prevalence of malnutrition remains high in our
      childhood population. This experiment was carried out to determine whether
      malnutrition is a factor contributing to an increase in the risk of damage
      associated with ozone exposure. METHODS: Using an experimental animal model, 21
      day-old rats fed normally or with induced malnutrition were subchronically
      exposed to 0.5 ppm of ozone or fresh air, respectively, for 30 days. At the end
      of this period and using HPLC, serotonin concentrations were measured in four
      areas of the brain: cortex, hemispheres, cerebellum, and medulla oblongata.
      RESULTS: Malnourished animals had a significant weight deficit beginning at 28
      days with respect to well-fed animals. Among the well-fed animals, this
      phenomenon is seen at 35 days in exposed and non-exposed animals. In the four
      regions of the brain, malnourished animals show low serotonin concentrations with
      respect to well-nourished animals. In the cerebellum, there was an interaction
      between the nutritional factor and ozone exposure, while in the medulla oblongata
      both factors acted independently. CONCLUSIONS: Our results suggest a
      multiplicative effect from the nutritional factor and ozone exposure in the
      changes observed concerning serotonergic metabolism.

PMID- 11825626
TI  - Detection of mucopolysaccharidosis type I heterozygotes based on the biochemical
      characteristics of leukocyte alpha-L-iduronidase.
AB  - BACKGROUND: In the present study, we biochemically characterized the enzyme alpha
      L-iduronidase (IDUA) of leukocytes from normal individuals and from
      mucopolysaccharidosis I (MPS I) heterozygotes, and compared these characteristics
      to discriminate for inclusion into two different groups. METHODS: We
      fluorimetrically measured IDUA activity in leukocytes using 4-methylumbelliferyl
      alpha-L-iduronide as an artificial substrate. Optimum pH, Km, Vmax, and
      thermostability of the enzyme at 50 degrees C were determined. RESULTS: Based on
      leukocyte IDUA activity, we divided the heterozygotes into two groups, one (group
      1) with activity below that detected in controls, and the other with activity
      similar to that of normal individuals (group 2). The optimum pH for IDUA was 2.7
      for normal individuals and 2.6-2.8 for heterozygotes. With respect to Km, there
      was a difference only between the value for normal IDUA (0.60 mM) and the value
      for group 2 (0.38 mM), while group 1 showed a statistically similar value (0.49
      mM). The Vmax of the reaction was discriminated in the three groups in a highly
      effective manner. The IDUA of normal individuals had a higher Vmax (60.98 nmoL/h
      x mg protein) than the enzyme of group 1 heterozygotes (28.66 nmoL/h x mg
      protein) and the enzyme of group 2 (31.78 nmoL/h x mg protein). When the IDUA
      from the three groups was pre-incubated at 50 degrees C, we observed that the
      IDUA of both group 1 and group 2 was significantly more thermostable than the
      IDUA of normal individuals. CONCLUSIONS: Determination of IDUA activity alone is
      not sufficient to discriminate between MPS I heterozygotes and normal individuals
      because a considerable overlap occurs between them. Our study showed that
      leukocyte IDUA from MPS I heterozygotes differed from the normal enzyme in terms
      of optimum pH, Km, and Vmax of the reaction and thermostability at 50 degrees C.
      These parameters provide a simple and reliable tool for the detection of carriers
      for MPS I.

PMID- 11825627
TI  - Brainstem auditory evoked response in HIV-infected patients with and without
      AIDS.
AB  - BACKGROUND: The purpose of this paper is to determine the type and frequency of
      brainstem auditory evoked potential abnormalities in HIV-infected patients with
      and without acquired immune deficiency syndrome (AIDS). METHODS: Brainstem
      auditory evoked potentials were performed in 44 HIV-infected patients; 22 of
      these patients were asymptomatic carriers and 22 presented clinical manifestation
      of AIDS at the time of the study. Twenty healthy young adults were studied as
      controls. When brainstem auditory evoked potentials were performed, none of the
      HIV-infected patients had neurologic clinical findings. RESULTS: The interwave
      intervals I-V showed significant differences (p <0.05) between both HIV-infected
      groups and the control group. There were non-significant differences between the
      two groups including HIV-infected patients with or without clinical features of
      AIDS. CONCLUSIONS: It is concluded that the HIV infection may produce subclinical
      pathologic changes in the cochlear nerve and brainstem, which can be detected by
      BAEP test.

PMID- 11825628
TI  - Effects of extremely low frequency electromagnetic fields on hematologic and
      immunologic parameters in welders.
AB  - BACKGROUND: Electric arc welding is known to cause considerable exposure to
      extremely low frequency magnetic fields. Although some studies of exposure to
      magnetic fields and epidemiologic studies have included groups of welders,
      typically little information is available concerning the hematologic and
      immunologic effects of ELF electromagnetic fields on welders. Therefore, the aim
      of the present study is to investigate whether or not extremely low frequency
      electromagnetic fields (ELF EMF) emitted from electric arc welding affect some
      hematologic and immunologic parameters of welders. METHODS: The study was carried
      out on 16 male welders and 14 healthy males between 20 and 40 years of age from
      the same geographic area and with similar life styles. The following hematologic
      and immunologic parameters were measured in both groups: red blood cells (RBC);
      hemoglobin (Hgb); hematocrit (Hct); platelets (Plt); total white blood cells
      (WBC); neutrophils; lymphocytes; eosinophils; and CD3, CD4, CD8, and CD4/CD8.
      RESULTS: Some of the hematologic and immunologic parameters under investigation
      were similar in both groups. Although T lymphocyte surface antigens, such as
      levels of CD4 and CD8(,) were found to be lower in the welders than in the
      control subjects (p <0.001, p <0.05), the hematocrit levels of the welders were
      found to be higher than those of the control subjects (p <0.05). However, the
      differences observed were not clinically significant. ELF electromagnetic field
      intensities in the welding areas varied between 0.10 and 0.25 mT. CONCLUSIONS:
      These results suggest that ELF electromagnetic fields do not affect the
      hematologic and immunologic parameters of welders.

PMID- 11825629
TI  - Validity of bone mineral density measurements in distal sites as an indicator of
      total bone mineral density in a group of pre-adolescent and adolescent women.
AB  - BACKGROUND: The study of bone mineral density (BMD) has received attention due to
      the importance of osteoporosis as a public health problem in Mexico. The
      objective of this study was to assess the validity of BMD measures in distal
      forearm and calcaneus with portable densitometers as indicators of BMD on other
      anatomic sites. METHODS: We conducted a cross-sectional study with 219 women from
      9 to 22 years of age in Cuernavaca, Morelos, Mexico. We measured BMD in central
      sites (the entire skeleton, excluding head, proximal femur, and lumbar spine)
      using dual X-ray absorptiometry (DXA) and in peripheral sites (distal forearm and
      calcaneus) using a portable densitometer with DXA technology. Measurements of
      height, weight, body composition, physical activity, and demographic
      characteristics were collected. Agreement of measurements of BMD was assessed
      using correlation and regression analysis, and the method proposed by Bland and
      Altman. RESULTS: Higher levels of BMD were found in total skeleton (0.88 g/cm(2))
      than in calcaneus (0.48 g/cm(2)) and distal forearm (0.38 g/cm(2)) (p <0.05).
      Moderate-to-high positive correlation coefficients (all significant) (p <0.05)
      were found between BMD in distal forearm and calcaneus vs. central anatomic
      sites, ranging from r = 0.49 to r = 0.78. BMD was higher in central sites
      compared with distal forearm and calcaneus. CONCLUSIONS: Measurement of BMD in
      distal forearm and calcaneus with portable densitometers provided valid
      indicators of BMD in central anatomic sites among pre-adolescent and adolescent
      women in Mexico.

PMID- 11825630
TI  - Newborn birth weight correlates with placental zinc, umbilical insulin-like
      growth factor I, and leptin levels in preeclampsia.
AB  - BACKGROUND: The aim of the present study was to determine whether newborn birth
      weights were associated with insulin-like growth factor I (IGF-I), zinc, and
      leptin in preeclamptic and normotensive pregnancies. METHODS: This study was done
      cross-sectionally and included 15 women with moderate preeclampsia (PE group) and
      11 normotensive pregnant women (NT group) of similar gestational age. Maternal
      and umbilical cord serum levels of zinc, IGF-I, IGF binding proteins (IGFBPs),
      leptin, and placental zinc were assessed in each group. RESULTS: As compared with
      the NT group, the PE group had significantly (p <0.05) lower newborn birth weight
      [3.33 (3.11-3.55) vs. 2.80 (2.40-3.17) kg], maternal IGF-I [303 (276-364) vs. 198
      (153-244) ng/mL], and umbilical IGF-I [87 (71-126) vs. 44 (26-98) ng/mL]. In
      addition, low IGFBP-3 and high IGFBP-1 were observed in the PE group. In the PE
      group, birth weight correlated positively with placental zinc (rho = 0.56, p =
      0.04), maternal IGF-I (rho = 0.76, p = 0.004), umbilical cord IGF-I (rho = 0.75,
      p = 0.005), and umbilical cord leptin (rho = 0.61, p = 0.02) levels. Stepwise
      multiple regression analysis showed that among these variables, umbilical IGF-I
      was the major predictor of birth weight. In the NT group, birth weight did not
      correlate with any of these variables. CONCLUSIONS: The present study indicates
      that moderate preeclampsia is associated with low newborn birth weight, IGF-I,
      IGFBP-3, and high IGFBP-1 without significant changes in zinc and leptin levels.
      In addition, umbilical IGF-I was the major predictor of newborn birth weight.

PMID- 11825631
TI  - Insulin subcutaneous application vs. continuous infusion for postoperative blood
      glucose control in patients with non-insulin-dependent diabetes mellitus.
AB  - BACKGROUND: Frequently, the use of insulin is considered for metabolic control in
      postoperative patients with non-insulin-dependent diabetes mellitus (NIDDM). We
      sought to determine the best method for control of glucose in NIDDM non-insulin
      patients during postoperative care. METHODS: Two algorithms were developed:
      subcutaneous administration of insulin (SC), and continuous intravenous infusion
      (IV). A randomized, controlled clinical trial was designed. In addition, both
      experimental groups were compared with a non-concurrent routinely managed group
      (RM) with insulin administration under no predetermined algorithm. Eligible
      patients were those subjected to major surgery under general anesthesia or spinal
      blockade. They were followed for 48 h after surgery. Target variables were
      capillary and central blood glucose, insulin dose administered, urine glucose and
      ketone strip determination, and development of hyper- or hypoglycemia. RESULTS: A
      total of 62 patients were studied (RM = 25, SC = 19, IV = 18). Results for both
      experimental algorithms were similar except for the IV group that required less
      insulin per hour compared to SC (0.64 vs. 0.34 U/h; p = 0.0003). The RM control
      group showed poor control in all capillary glucose measurements (194.9 +/- 26.8
      mg/dL) compared with the two experimental algorithms (SC = 129.9 +/- 21; IV =
      131.6 +/- 20.4) (p <0.05). More hyperglycemia events appeared in the RM group (p
      = 0.016). Only one hypoglycemia event occurred in the IV group. CONCLUSIONS:
      Postoperative control of NIDDM is similar with both tested methods. The use of
      any of the algorithms studied improves metabolic control substantially because it
      standardizes postoperative management of the diabetic patient with timely
      determination of capillary blood glucose and insulin administration. However, IV
      administration has the advantage of accomplishing adequate control with a smaller
      insulin dose.

PMID- 11825632
TI  - Risk factors associated with depression in patients with type 2 diabetes
      mellitus.
AB  - BACKGROUND: This study was undertaken in order to identify the prevalence and
      factors associated with depression in a group of patients with type 2 diabetes
      mellitus. METHODS: Our design consisted of a cross-sectional study at the
      Department of Neurology and Psychiatry of the Instituto Nacional de Ciencias
      Medicas y Nutricion Salvador Zubiran in Mexico City. Study units included 189
      patients with type 2 diabetes mellitus (DM). Beck Depression Inventory scale was
      used to measure the presence of depression, while the independent variables
      evaluated to explain depression were sociodemographic (gender, marital status,
      religion, education, occupation, socioeconomic status) and characteristics of the
      disease were disease duration, comorbidity, compliance, and glycemic control.
      RESULTS: Prevalence of depression was 39% (74 patients). The following risk
      factors were identified by univariate analysis: being widowed (OR 3.54,
      confidence interval [CI] 1.56-8.11, p = 0.0007); female (OR 2.95, CI 1.50-5.82, p
      = 0.006); housewife (OR 2.08, CI 1.10-3.94, p = 0.01); poor compliance (OR 2.14,
      CI 1.12-4.10, p = 0.01), and presence of comorbidity (OR 5.60, CI 1.51-24.5, p =
      0.002). On the other hand, the most constant associations were presence of blood
      glucose at the last appointment >or=200 (OR 3.23, CI 1.59-6.60, p = 0.0003) and
      >or=250 (OR 2.15, CI 0.93-5.03, p = 0.05), as the average of the last five blood
      glucoses >or=200 (OR 3.67, CI 1.76-7.73, p = 0.0001), >or=250 (OR 4.07, CI 1.61
      10.49, p = 0.0007) and >or=300 (OR 2.12, CI 1.48-3.02, p = 0.003). Discriminant
      function analysis of the variables, previously studied in univariate analysis,
      was carried out for the presence of depression. A stepwise model included the
      following variables: average of the last five blood glucoses; 2) widowed or
      divorced, and 3) female. CONCLUSIONS: Frequency of depression in patients with
      type 2 DM was high (39%). High level of blood glucose stands out as a variable
      associated with presence of depression. Other associations were presence of
      comorbidity, being a female, and being widowed or divorced.

PMID- 11825633
TI  - Changing risk factors for HIV infection.
AB  - BACKGROUND: HIV infection in women is a growing problem in developing countries.
      Risk factors for HIV infection vary from country to country and may change with
      time. METHODS: We describe a retrospective review of the epidemiologic
      characteristics and associated gynecologic diseases of all HIV-infected women
      seen at two tertiary-care hospitals in Mexico City. RESULTS: One hundred thirty
      consecutive patients were included in the study from March 1985 to January 1996.
      Mean age at HIV diagnosis was 36.2 years (range: 16-76). Of the 75 women
      diagnosed with AIDS prior to 1992, 58 (69%) were infected through blood
      transfusion and 17 (20%) through sexual contact. After January 1992, 11 (23%)
      acquired infection through blood transfusion and 28 (60%) through sexual contact;
      these differences were statistically significant (p <0.0001). Prior to 1992, 66
      (90%) women presented in stage IV, whereas after that year only 29 (51%) (p
      <0.001) presented in stage IV. Of 92 patients on whom a cervico-vaginal smear was
      carried out, human papillomavirus infection was identified in 22 (24%) women,
      nine (9.8%) had morphologic evidence of a cervical intraepithelial neoplasia
      (four with mild or moderate dysplasia and five with in situ cervical carcinoma).
      Four patients had invasive cervical carcinoma. CONCLUSIONS: The main risk factor
      for HIV infection in Mexican women with AIDS changed from transfusion acquired to
      sexually acquired in 1992. As a country, we were successful in providing safe
      blood but failed to prevent sexual transmission. Our patients had a high
      frequency of cervical carcinoma and precursor lesions associated with human
      papilloma virus.

PMID- 11825634
TI  - A two-dose combined vaccine against hepatitis A and hepatitis B in healthy
      children and adolescents compared to the corresponding monovalent vaccines.
AB  - BACKGROUND: Immunization against hepatitis A and B has been available for some
      time, protecting against both infections. With a view to achieving further
      reduction in the number of interventions and increasing convenience of the
      vaccinee, we investigated the reactogenicity and immunogenicity of a combined
      hepatitis A and B vaccine in healthy 4- to 20-year-old subjects at a 0, 6-month
      schedule. METHODS: Two hundred forty-eight study subjects were allocated to two
      study groups and received either two doses of the combined hepatitis A and B
      vaccine (68% of subjects) or the corresponding monovalent hepatitis A and
      hepatitis B vaccines (32% of subjects) concomitantly in opposite arms.
      Reactogenicity was assessed via diary cards after each vaccination. Serum samples
      were analyzed at months 1, 2, 6, and 7. RESULTS: All vaccines were well tolerated
      and very few symptoms were scored as severe. All but one subject seroconverted
      for anti-hepatitis A virus (anti-HAV) antibodies (98.6%) and 100% of subjects
      seroconverted for anti-hepatitis B (HBs) antibodies, with respective
      seroprotection rates of 98.7% for the combined vaccine group and 95.9% for the
      concomitant vaccine group (p >0.05), respectively. Geometric mean titers were
      higher in the group receiving the combined vaccine: 6,635 mIU/mL vs. 2,728 mIU/mL
      (p = 0.0001) for anti-HAV and 3,362 mIU/mL vs. 1,724 mIU/mL (p = 0.0205) for anti
      HBs, respectively. Younger subjects had a stronger immune response compared to
      older subjects. CONCLUSIONS: The combined hepatitis A and B vaccine was well
      tolerated at this two-dose schedule. The combined vaccine had higher
      immunogenicity, probably explained by a adjuvant effect of the antigens.
      Vaccination programs requiring fewer injections will most likely have a positive
      impact on compliance rate and comfort of the vaccinee.

PMID- 11825635
TI  - Consumption of fruits, vegetables, soft drinks, and high-fat-containing snacks
      among Mexican children on the Mexico-U.S. border.
AB  - BACKGROUND: The recommended diet for children would promote health, support
      growth, and prevent risk of disease. Diets high in fruits and vegetables
      demonstrate a strong and consistent pattern for decreasing the risk for many
      cancers and providing benefits against cardiovascular disease, diabetes, obesity,
      and stroke. The purpose of this study was to assess fruit, vegetable, soft drink,
      and high-fat-containing snack consumption among fifth- and ninth-grade children
      attending public schools in the northeastern Mexican state of Baja California.
      METHODS: A randomized design was used to select 20 schools with fifth-grade
      students and 20 schools with ninth-grade students in each of the five Baja
      California counties. A randomized sample of 20 classes of fifth- and ninth-grade
      students was then selected. The food frequency questionnaire used contained 36
      items. Foods were grouped in the five main food categories, plus soft drinks,
      sweets, and high-fat-containing snacks. Means, standard deviations (SDs), and
      frequencies were calculated using SPSS, while chi square was employed to test the
      association between food consumption and selected variables. RESULTS: Mean daily
      intake of fruits was 1.5 by children from both grades, while daily mean intake of
      vegetables was 2.5 for fifth-grade students. The percentage of children with
      intakes lower than the standard (Apple of Health) was 77 and 80% for fifth and
      ninth graders for fruits and 62 and 53% for vegetables, respectively. At least
      92% of fifth graders reported consuming one soft drink, and 85% consumed one
      portion of high-fat-containing snacks daily. CONCLUSIONS: Our results
      demonstrated overall low intake of fruits and vegetables and excessive
      consumption of soft drinks and high-fat-containing snacks, leading to the
      possibility of costly health complications later in life.

PMID- 11825636
TI  - Iron stores in low-income pregnant Mexican women at term.
AB  - BACKGROUND: Iron stores can be depleted during pregnancy. Serum ferritin is the
      most useful non-invasive test to assess iron stores in women of reproductive age.
      Iron status of pregnant Mexican women at term from a low-income group was
      investigated through serum ferritin determinations. METHODS: Hemoglobin and serum
      ferritin were measured in 201 low-income urban women with at-term pregnancy
      receiving attention at a public university hospital. Hemoglobin cut-off value was
      110.0 g/L. Depending on their serum ferritin concentration, women were divided
      into three groups: group I, iron deficiency, serum ferritin <12 microg/L; group
      II, borderline iron stores, serum ferritin >or=12 microg/L and <30 microg/L, and
      group III, normal iron stores, serum ferritin >or=30 microg/L. RESULTS: Mean SF
      value in the entire group was 7.0 +/- 6.4 microg/L, with a mean Hb of 110.1 +/-
      15.8 g/L. One hundred seventy-two women (85.6%) had empty iron stores. Ninety-two
      women (46%) in the entire group had iron deficiency anemia, as did 79 (46%) of
      the 172 iron-deficient women. During their pregnancy, 165 women (82%) did not
      ingest any supplemental iron and 131 (65%) did not receive any prenatal care.
      CONCLUSIONS: We documented a high prevalence of iron deficiency and iron
      deficiency anemia, together with practically no prenatal care utilization and no
      supplemental iron ingestion in this low-income group. A serum ferritin
      concentration >or=12 microg/L was always accompanied by a normal hemoglobin
      concentration. These data suggest that prenatal care and iron supplementation may
      be considered as major determinants of maternal iron stores to prevent iron
      deficiency anemia.

PMID- 11825637
TI  - Blink reflex and discomplete facial nerve palsy.
AB  - BACKGROUND: Electrophysiologic findings of the blink reflex in patients with
      Bell's palsy are usually said to be either prolonged latencies and/or absent
      early and middle responses of it. METHODS: Facial nerve conduction and blink
      reflex studies were performed on a 42-year-old male patient with right-side
      Bell's palsy. Studies were done using protocols previously validated and
      published elsewhere. RESULTS: The right compound muscle action potential was not
      found after stimulation of the right facial nerve as expected. Absence of the
      short (R1) and middle (R2) responses of the blink reflex were also noted after
      right and left supraorbital nerve stimulation. Further, the late (R3) response of
      the blink reflex was displayed on the abnormal side when electrical stimuli were
      applied to the right supraorbital nerve while the patient attempted to perform
      voluntary movement of the paralyzed facial muscles including eye closing.
      CONCLUSIONS: The recording of R3-a late response following fibers and using
      motoneurons other than those employed by R1 and R2-on the paralyzed side after
      performing some reinforcement maneuvers allows us to suggest that, in some facial
      nerve palsies, there are some structures remaining alive that may be useful for
      carrying out a more timely and accurate diagnosis and follow-up.

PMID- 11825638
TI  - Informed consent to participate in research.

PMID- 11825640
TI  - Distribution of pancreatic polypeptide and peptide YY.
AB  - The cellular distribution of PP and PYY in mammals is reviewed. Expression of PP
      is restricted to endocrine cells mainly present in the pancreas predominantly in
      the duodenal portion (head) but also found in small numbers in the gastro
      intestinal tract. PYY has a dual expression in both endocrine cells and neurons.
      PYY expressing endocrine cells occur all along the gastrointestinal tract and are
      frequent in the distal portion. Islet cells expressing PYY are found in many
      species. In rodents they predominate in the splenic portion (tail) of the
      pancreas. A limited expression of PYY is found also in endocrine cells in the
      adrenal gland, respiratory tract and pituitary. Peripheral, particularly enteric,
      neurons also express PYY as does a restricted set of central neurons.

PMID- 11825642
TI  - The origin and evolution of peptide YY (PYY) and pancreatic polypeptide (PP).
AB  - It is generally accepted that the neuropeptide Y (NPY) family of homologous
      peptides arose as a result of a series of gene duplication events. Recent
      advances in comparative genomics allow to formulate a hypothesis that explains,
      at least in part, the complexity of the family. Chromosome mapping studies reveal
      that the gene encoding PYY may have arisen from a common ancestral gene (termed
      NYY) in an ancient chromosomal duplication event that also involved the hox gene
      clusters. A tandem duplication of the PYY gene concomitant with or just before
      the emergence of tetrapods generated the PPY gene encoding PP. In the primate and
      ungulate lineages, the PYY-PPY gene cluster has undergone a more recent gene
      duplication event to create a PYY2-PPY2 gene cluster on the same chromosome. In
      the human and baboon, this cluster probably does not encode functional NPY family
      peptides but expression of the bovine PYY2 gene generates seminalplasmin, a major
      biologically active component of bull semen. An independent duplication of the
      PYY gene in the lineage of teleost fish has generated peptides of the PY family
      that are synthesized in the pancreatic islets of Acanthomorpha. The structural
      organization of the biosynthetic precursors of PYY and PP (preproPYY and
      preproPP) has been quite well preserved during the evolution of vertebrates but
      conservative pressure on individual domains in the proteins has not been uniform.
      The duplication of the PYY gene that generated the PPY gene appears to have
      resulted in a relaxation of conservative pressure on the functional domain with
      the result that the amino acid sequences of tetrapod PYYs are more variable than
      the PYYs of jawed fish. Although the primary structure of PP has been quite
      strongly conserved in mammals, with the exception of the rodents, the extreme
      variability in the sequences of amphibian and reptilian PPs means that the
      peptide is a useful molecular marker to study the branching order in early
      tetrapod evolution

PMID- 11825641
TI  - Ontogeny and the effect of aging on pancreatic polypeptide and peptide YY.
AB  - Pancreatic polypeptide (PP) and peptide YY (PYY) are related neuroendocrine
      peptides that are expressed in specialized cells. PP is found around the time of
      birth in different species. PYY in mice and rats has been extensively studied.
      PYY is the first peptide hormone to appear in both the pancreas and the colon and
      is initially expressed together with all other pancreatic islet and gut hormones.
      This suggests that there is a PYY-producing endocrine progenitor cell, at least
      in rodents. Whether the same is true for other species is unknown. In chickens,
      however, pancreatic insulin and glucagon cells appear before PYY. After birth,
      PYY levels in rats and humans reflect adaptation to enteral feeding. Whereas PYY
      cells increase with age in rodents, no such changes have been found in humans.

PMID- 11825643
TI  - Multiple regulation of peptide YY secretion in the digestive tract.
AB  - In the last two decades, multiple aspects of the peptide YY (PYY) secretion have
      been investigated. Besides fat and fatty acids, many luminal nutrients in the
      distal intestine appear to induce PYY release. Some studies have shown that bile
      acid, but not nutrients, plays a crucial role in the regulation of PYY secretion.
      Moreover, chyme in the proximal intestine also regulates the peptide release by
      indirect action through humoral and neuronal factors. Gastrin, cholecystokinin,
      and the vagus nerve are major candidates for mediators of these indirect actions.
      Several growth factors have been shown to regulate PYY synthesis in mucosa of the
      distal intestine. This review is aimed at presenting an overview of these recent
      studies on PYY secretion in the distal intestine.

PMID- 11825644
TI  - Pancreatic polypeptide receptors: affinity, sodium sensitivity and stability of
      agonist binding.
AB  - Cloned rat, human and guinea-pig Y4 pancreatic polypeptide (PP) receptors
      expressed in Chinese hamster ovary (CHO) cells, as well as the rabbit Y4-like PP
      receptor, show a selective sensitivity to Na+ over K+ ion in PP attachment, but
      little sensitivity to Na+ in dissociation of bound PP peptides. Agonist binding
      to Y4 receptors of intact CHO cells also shows much greater sensitivity to Na+
      over K+, and a tenacious attachment of the bound agonist. Binding sensitivity to
      K+ is greatly enhanced upon receptor solubilization. Pancreatic polypeptide sites
      also show large sensitivity to modulators of Na+ transport such as N5-substituted
      amilorides and to RFamides, as different from Y1 or Y2 receptors. Thus, PP
      binding is modulated by cation-induced changes in site environment (with
      selectivity for Na+) and ultimately results in a blocking attachment. This would
      support receptor operation in the presence of ion gradients, as well as prolonged
      agonist-delimited signaling activity (which can include partial antagonism).
      Also, this could point to an evolutionary adaptation enabling small numbers of PP
      receptors to perform extensive metabolic tasks in response to low agonist
      signals.

PMID- 11825646
TI  - Roles of pancreatic polypeptide in regulation of food intake.
AB  - Pancreatic polypeptide (PP) is produced in pancreatic islets of Langerhans and
      released into the circulation after ingestion of a meal. Peripherally
      administered PP suppresses food intake and gastric emptying. On the other hand,
      central administration of PP elicits food intake and gastric emptying. Therefore,
      PP actions on food intake may be, in part, attributable to gastric emptying. PP
      transgenic mice exhibit decreases in both food intake and gastric emptying rate
      that were clearly reversed by anti-PP antiserum. PP is an anorexigenic signal in
      the periphery and an orexigenic signal in the central nervous system.

PMID- 11825645
TI  - Structure and receptor binding of PYY analogs.
AB  - Differences in the structure of PYY and two important analogs, PYY [3-36] and
      [Pro34]PYY, are evaluated. Y-receptor subtype ligand binding data are used in
      conjunction with structural data to develop a model for receptor subtype
      selective agonists. For PYY it is proposed that potent binding to Y1, Y4 and Y5
      receptors requires the juxtaposition of the two termini while Y2 binding only
      requires the C-terminal helix. Further experiments that delineate between primary
      and tertiary structure contributions for receptor binding and activation are
      required to support the hypothesis that tertiary structure is stable enough to
      influence the expression of PYY's bioactivity.

PMID- 11825647
TI  - Pancreatic polypeptide in pancreatitis.
AB  - Pancreatitis is a disease with increasing incidence which can be divided into an
      acute and a chronic form. In both acute and chronic pancreatitis, changes in
      plasma concentration of pancreatic polypeptide (PP) and its regulation have been
      reported. In daily clinical work a serologic test for the precise diagnosis and
      staging of acute and chronic pancreatitis is still desirable. Therefore, many
      studies have investigated plasma concentrations of PP in acute and chronic
      pancreatitis as a diagnostic marker and as a therapeutic option to treat
      pancreatogenic diabetes mellitus. Although the study results are presently
      inconclusive and potentially contradictory, the findings are nevertheless
      encouraging, and indicate that PP might have a role in diagnosis, grading and
      estimation of the prognosis of pancreatitis. Further data and prospective
      controlled studies are needed to judge whether PP is of clinical value for
      diagnosing, staging and predicting long-term outcome in acute and chronic
      pancreatitis.

PMID- 11825648
TI  - Pancreatic polypeptide-related tumors.
AB  - PP-producing tumors are mostly located in the pancreas and may present as three
      pathologic lesions: pure PP-omas, mixed tumors with minor PP cell population, and
      PP-cell hyperplasia. These tumors are among the most common multiple adenomas
      frequently found in patients with multiple endocrine neoplasia type 1.
      Hypersecretion and high circulating levels of PP are frequently found. They are
      symptomless but may be useful for the identification of the pancreatic tumors.
      Numerous types of extrapancreatic endocrine tumors are able to synthesize and
      secrete PP. They occur mostly but not exclusively in the gastrointestinal tract,
      particularly in the rectum. The inactivation of the MEN 1 gene at 11q13 appears
      to be involved in the development of pancreatic but not of rectal PP-producing
      tumors.

PMID- 11825649
TI  - Central and peripheral regulation of gastric acid secretion by peptide YY.
AB  - Peptide YY (PYY) released postprandially from the ileum and colon displays a
      potent inhibition of cephalic and gastric phases of gastric acid secretion
      through both central and peripheral mechanisms. To modulate vagal regulation of
      gastric functions, circulating PYY enters the brain through the area postrema and
      the nucleus of the solitary tract, where it exerts a stimulatory action through
      PYY-preferring Y1-like receptors, and an inhibitory action through Y2 receptors.
      In the gastric mucosa, PYY binds to Y1 receptors in the enterochromaffin-like
      cells to inhibit gastrin-stimulated histamine release and calcium signaling via a
      pertussis toxin-sensitive pathway.

PMID- 11825650
TI  - Feedback regulation of pancreatic secretion by peptide YY.
AB  - The present status of our understanding of the feedback regulation of pancreatic
      secretion by peptide YY (PYY) released from the distal intestine is reviewed.
      Exocrine pancreatic secretion is primarily controlled by the cephalic (the vagus
      nerve), gastric (acid and pepsin secretion, and nutrients delivered into the
      duodenum by gastric emptying), and intestinal (secretin and CCK) mechanisms. PYY
      acts on the multiple sites in the brain and gut, and inhibits pancreatic
      secretion by regulating these primary control mechanisms. The involvement of Y(1)
      and Y(2) receptors has been suggested in the regulation of pancreatic secretion.
      However, it remains to be studied which site of action or receptor subtype is
      physiologically most important for this regulation.

PMID- 11825651
TI  - PYY-mediated fatty acid induced intestinal differentiation.
AB  - An essential process for fatty acid digestion, absorption and assimilation is the
      constant replacement of mature intestinal epithelial cells by differentiating
      stem cells. Free fatty acids (FFA) and PYY may act in concert to alter mucosal
      cell differentiation through the cytoskeletal-extracellular matrix interactions.
      PYY induced expression of tetraspanins and intestinal fatty acid binding protein
      (I-FABP) may be part of a mechanism whereby FFA modulate expression of
      differentiation dependent proteins in the mucosa. This modulation provides a
      means for FFA to act as signal molecules in the feedback regulation of their own
      assimilation.

PMID- 11825652
TI  - Peptide YY: a key mediator of orexigenic behavior.
AB  - Peptide YY (PYY) is the most potent orexigenic peptide or substance known.
      However, neither the underlying physiology of this hyperphagia nor PYY's natural
      role in brain are well understood. Thus, this review details the neuroanatomical
      sites, the neurochemical and systemic interactions, the food-related properties
      and the motivational factors that characterize hyperphagia elicited by central
      PYY. Emphasis also is given to evidence that central PYY has properties
      functionally distinct from neuropeptide Y. Finally, future research directions
      are outlined that aim at accelerating our understanding of the roles that brain
      PYY and PYY-preferring receptors occupy in normal and abnormal feeding behavior.

PMID- 11825653
TI  - Peptide YY as a growth factor for intestinal epithelium.
AB  - Peptide YY is an abundant distal gut hormone that may play a significant role in
      intestinal epithelial proliferation. Gut epithelial cells express specific
      receptors for PYY, PYY induces proliferation in intestinal cells in vivo and in
      vitro, and the Y1 receptor subtype couples to mitogenic signaling pathways. In
      addition to proposed physiologic effects on gut mucosal maintenance, PYY
      proliferative effects may be hypothesized to contribute to pathophysiologic
      consequences of stimulated growth.

PMID- 11825654
TI  - Peptide YY and cancer: current findings and potential clinical applications.
AB  - Peptide YY (PYY) is a naturally occurring gut hormone with mostly inhibitory
      actions on multiple tissue targets. PYY has been identified in several carcinoid
      tumors and a decreased expression of PYY may be relevant to the development and
      progression of colon adenocarcinoma. Treatment with PYY decreases growth in
      pancreatic and breast tumors, most likely through a reduction in intracellular
      cAMP. In cancer patients, PYY may also improve malnutrition that results from
      iatrogenic causes or cachexia associated with advanced disease. PYY plays a
      significant role in multiple aspects of cancer from regulation of cell growth to
      potential therapeutic applications.

PMID- 11825655
TI  - Peptide YY in gastrointestinal disorders.
AB  - The changes in PYY in several gastrointestinal disorders and their possible
      clinical implications are reviewed. The changes in PYY seem to be an adaptive
      response to alterations in the patho-physiological condition caused by the
      disease. This becomes evident in gastrointestinal disorders such as diabetes
      gastroenteropathy, inflammatory bowel diseases, celiac disease, systemic
      sclerosis and post-intestinal resection state. On the other hand, changes in PYY
      in chronic idiopathic slow transit constipation appear to be primary and could be
      one of the etiologic factors of the disease. PYY does not seem to be involved in
      colorectal carcinoma. Although gastrointestinal dysmotility in neuro-muscular
      diseases is evident, PYY is not affected. The changes in PYY in gastrointestinal
      disorders could be beneficial in clinical practice. Thus, in cases where an
      increase or decrease in PYY is desirable, a diet that increases or decreases PYY
      synthesis and release can be followed, or a receptor agonist or antagonist can be
      utilized.

PMID- 11825656
TI  - Effects of surgical manipulation of the intestine on peptide YY and its
      physiology.
AB  - PYY is a gastrointestinal hormone, mainly released from the distal intestine in
      response to intraluminal nutrients or via a neurohormonal pathway originating in
      the proximal intestine. Although there are several molecular forms of circulating
      PYY with different bioactivity, and further more than six subtypes of Y
      receptors, the function is essentially inhibitory to digestive organs located
      upstream of the digestive tract. These inhibitory mechanisms are named jejunal,
      ileal and colonic brakes, and play an important supplementary role in adaptation
      following intestinal resection. When massive resection of the small intestine is
      performed, the release of PYY from the distal intestine increases, suppressing
      gastric acid secretion and motility of the gastrointestinal tract, and
      stimulating pancreatic secretion. After total colectomy, PYY release is reduced
      first due to reduction of PYY-containing cells, then gradually increases with
      time, contributing to adaptation of the digestive organs to the new condition.

PMID- 11825657
TI  - Convergence of mitogenic and DNA damage signaling in the G1 phase of the cell
      cycle.
AB  - Research into the molecular basis of cancer has a central tenet. Cancer arises
      from genetic alterations that disconnect growth and differentiation signaling
      pathways from the machinery that regulates cellular proliferation. In multi
      cellular eukaryotes, proliferation is regulated by external signals, such as the
      availability of growth factors and nutrients and by internal signals, such as
      those sensing cellular integrity. Cellular stress created either by lack of
      mitogens or damage to cellular components, such as DNA, stimulates responses that
      enforce temporal or permanent withdrawal from the cell cycle. Although these
      stress responses stem from different sources and activate distinct pathways, they
      converge on the same components of the cell cycle machinery in the G1 phase of
      the cell cycle. This review will highlight and compare aspects of the G1 arrest
      in response to stress generated either by lack of mitogens or damage to DNA.

PMID- 11825658
TI  - Cancer chemopreventive effects of constituents of Caesalpinia ferrea and related
      compounds.
AB  - The anti-tumor promoting effects of fruits of Caesalpinia ferrea MART.
      (Leguminosae) were tested by the in vitro Epstein-Barr virus early antigen (EBV
      EA) activation assay, and its active constituents were identified as gallic acid
      (1) and methyl gallate (2). A total of 49 related compounds of 1 and 2 were
      analysed for the effects by this assay, and the structure activity relationships
      have been proposed. Three acetophenone derivatives, 2,6-dihydroxyacetophenone
      (48), 2,3,4-trihydroxyacetophenone (50) and 2,4,6-trihydroxy- acetophenone (51)
      were found to show potent inhibitory activity.

PMID- 11825659
TI  - Expression and mutation of p53 gene in the lung of mice intratracheal injected
      with crystalline silica.
AB  - The genotoxic effect of crystalline silica (Qt) in the lung was studied to
      clarify that silicosis conferred a significant increase in risk subsequent lung
      cancer. C57BL/6N mice received a single tracheal injection of Qt at dose of 2
      mg/mouse. Lung p53mRNA was suppressed significantly, but no change of p21mRNA 15
      months after treatment. Mutation of p53 gene was not identified at 15 months in
      the Qt group. Silicotic lesions were observed in the lungs of Qt group, but
      silicosis with pulmonary neoplasia was no detected. These results indicated that
      genetic changes in the silicotic lung might lead to facilitation of
      carcinogenesis.

PMID- 11825660
TI  - Role of mitochondrial complexes I and II, reactive oxygen species and arachidonic
      acid metabolism in deoxycholate-induced apoptosis.
AB  - Bile acids are promoters of colon cancer; however, the mechanism(s) of action of
      this tumor promoter are largely unknown. Bile acids induce apoptosis in colon
      epithelial cells and it is probable that the modulation of apoptosis contributes,
      in part, to colon carcinogenesis. We tested the hypothesis that damage to
      mitochondria is an upstream event in sodium deoxycholate (NaDOC)-induced
      apoptosis and that a pro-oxidant state of the cell favors survival. NaDOC-induced
      damage to mitochondria was assessed by a decrease in mitochondrial membrane
      potential using flow cytometry and an increase in megamitochondria formation
      using transmission electron microscopy. We found that inhibition of mitochondrial
      complexes I and II with rotenone and thenoyltrifluoroacetone, respectively,
      dramatically protected HT-29 cells against NaDOC-induced apoptosis. Antioxidants
      (e.g. lazaroids U-74389G and U-8389G), however, sensitized cells to NaDOC-induced
      apoptosis, in spite of a reduction in reactive oxygen/nitrogen species. Lazaroid
      pre-treatment caused a marked decrease in NaDOC-induced activation of the anti
      apoptotic transcription factor, NF-kappaB, which may provide the basis for the
      sensitization to apoptosis caused by these antioxidants. Inhibitors of
      arachidonic acid metabolism (e.g. esculetin, sulindac sulfide, NS-398) also
      sensitized HT-29 cells to NaDOC-induced apoptosis. These results indicate that
      the life/death decision is the result of a shift in the balance between specific
      anti-apoptotic and pro-apoptotic factors, respectively, that may have
      significance to colon carcinogenesis.

PMID- 11825661
TI  - Rosemary-stimulated reduction of DNA strand breaks and FPG-sensitive sites in
      mammalian cells treated with H2O2 or visible light-excited Methylene Blue.
AB  - In this study possible protective effects of rosemary against oxidative DNA
      damage induced by H2O2- and visible light-excited Methylene Blue in colon cancer
      cells CaCo-2 and hamster lung cells V79 were investigated. The level of DNA
      damage (DNA strand breaks) was measured using the classical and modified single
      cell gel electrophoresis, so-called comet assay. Our findings showed that an
      ethanol extract from rosemary reduced the genotoxic activity of both agents after
      a long-term (24 h; 0.3 microg/ml) or short-term (2 h; 30 microg/ml) pre
      incubation of cells. We suggest that the extract of rosemary exhibits a
      protective effect against oxidative damage to DNA as a consequence of scavenging
      of both *OH radicals and singlet oxygen ((1)O2).

PMID- 11825662
TI  - Suppression of promoter-dependent transcriptional activity of inducible nitric
      oxide synthase by sodium butyrate in colon cancer cells.
AB  - Butyrate suppresses the growth of colon cancer cells, inducing differentiation
      and apoptosis in vitro. Increased expression of inducible nitric oxide synthase
      (iNOS) and cyclooxygenase-2 (COX-2) has been suggested to be closely involved in
      colon carcinogenesis. In this study, effects of sodium butyrate on the promoter
      dependent transcriptional activity of iNOS and COX-2 genes were investigated in a
      colon cancer cell line, DLD-1, using a reporter gene assay system. Sodium
      butyrate significantly reduced promoter-dependent iNOS transcriptional activity
      dose-dependently at concentrations higher than 0.1 mM. COX-2 transcriptional
      activity was not suppressed, but slightly increased. While hyperacetylated
      histones appeared at concentrations of sodium butyrate suppressing iNOS gene
      promoter activity, promoter-dependent transcriptional activities of iNOS and COX
      2 genes were both increased by the histone deacetylase inhibitor trichostatin A.
      These results suggested that sodium butyrate exhibits differential effects on
      iNOS and COX-2 genes, acting to suppress iNOS expression via mechanisms
      independent of histone acetylation.

PMID- 11825663
TI  - The antiproliferative effects of biologically active isomers of conjugated
      linoleic acid on human colorectal and prostatic cancer cells.
AB  - The antiproliferative effects of two commercial preparations of conjugated
      linoleic acid (CLA) and their constituent isomers, cis-9, trans-11 (c9,t11)-CLA,
      c9,c11-CLA, and t10,c12-CLA, were determined in vitro using human colorectal (HT
      29, MIP-101) and prostate (PC-3) carcinoma cells adapted to serum-free medium.
      The antiproliferative effects of the preparations were dependent upon the type
      and concentration of CLA isomer present. The t10,c12-CLA isomer exhibited the
      greatest potency against colorectal cancer proliferation, and the c9,t11 and
      t10,c12 isomers were moderately effective against prostate cancer. The t10,c12
      isomer induced caspase-dependent apoptosis in MIP-101 and PC-3 cells. The results
      are the first to demonstrate that physiologic levels of two CLA preparations,
      their constituent isomers, and the c9,t11-CLA elongation product, c11,t13
      conjugated eicosadienoic acid, induce dose-dependent inhibitory effects on cancer
      proliferation in vitro. Novel CLA preparations may prove effective as
      chemopreventive supplements for individuals at risk of or diagnosed with
      colorectal or prostate cancer.

PMID- 11825664
TI  - Combined effect of glutathione S-transferase M1 and T1 genotypes on bladder
      cancer risk.
AB  - To evaluate the association between genetic polymorphism of GSTM1, GSTT1 and
      development of bladder cancer, a hospital-based case-control study was conducted
      in South Korea. The study population consisted of 232 histologically confirmed
      male bladder cancer cases and 165 male controls enrolled from urology departments
      with no previous history of cancer or systemic diseases in Seoul during 1997
      1999. The GSTM1 null genotype was significantly associated with bladder cancer
      (OR: 1.6, 95% CI: 1.0-2.4), whereas the association observed for GSTT1 null
      genotype did not reach statistical significance (OR: 1.3, 95% CI: 0.9-2.0). There
      was a statistically significant multiple interaction between GSTM1 and GSTT1
      genotype for risk of bladder cancer (P=0.04); the risk associated with the
      concurrent lack of both of the genes (OR: 2.2, 95% CI: 1.2-4.3) was greater than
      the product of risk in men with GSTM1 null/GSTT1 present (OR: 1.3, 95% CI: 0.7
      2.5) or GSTM1 present/GSTT1 null (OR: 1.1, 95% CI: 0.6-2.2) genotype
      combinations.

PMID- 11825665
TI  - The bradykinin/soluble guanylate cyclase signaling pathway is impaired in
      androgen-independent prostate cancer cells.
AB  - The activation of soluble guanylate cyclase by bradykinin and sodium
      nitroprusside (SNP), a direct activator of soluble guanylate cyclase, was
      evaluated in androgen-sensitive LNCaP and androgen-independent PC3 and DU145
      prostate cancer cells. Bradykinin and SNP activated soluble guanylate cyclase in
      LNCaP cells, but not in PC3 and DU145 cells. Western blot analysis revealed that
      the bradykinin B2 receptor, Gqalpha, phospholipase Cgamma and endothelial nitric
      oxide synthase were expressed in LNCaP, PC3 and DU145 cells. However, both
      Western blotting and reverse transcriptase--polymerase chain reaction indicated
      that soluble guanylate cyclase was only expressed in LNCaP cells. These results
      demonstrate that the impaired bradykinin-soluble guanylate cyclase pathway in PC3
      and DU145 cells is likely due to lack of expression of soluble guanylate cyclase.

PMID- 11825666
TI  - Effect of Bcl-2 expression on hepatic preneoplasia in mice.
AB  - In a transgenic model of hepatocellular carcinoma induced by the expression of
      SV40 early sequences (TAg mice), deregulation of hepatocyte proliferation induces
      an apoptotic process whose decrease coincides with the appearance of neoplastic
      foci. Mating these mice with transgenic mice overexpressing Bcl-2 led to a
      dramatic reduction in the number of apoptotic hepatocytes during preneoplasia,
      resulting in an enlargement of the liver. This decrease in apoptosis was
      followed, 2 weeks later, by a reduction in hepatocellular proliferation.
      Sequential reduction in apoptosis and proliferation rate suggests that the anti
      apoptotic and the anti-mitotic activities of Bcl-2 might be operative in distinct
      stages of preneoplasia.

PMID- 11825667
TI  - Lysophosphatidic acid induces glycodelin gene expression in cancer cells.
AB  - Glycodelin is a glycoprotein that has been suggested to be important in normal
      pregnancy and in malignancy. The regulation of its synthesis has not been
      studied. In this study, we report the induction of glycodelin gene expression by
      lysophosphatidic acid (LPA). We studied the effect of LPA (5, 10 and 25 microM)
      on glycodelin production in breast (MDA-MB-231), cervical (Hela), endometrial (RL
      95), ovarian cancer (OVCAR-3) and erythroleukemia (K562) cells. There was a dose
      dependent (5-25 microM) induction of glycodelin gene and protein expression in
      these cell types. LPA is a mimic of phorbol myristate acetate (PMA) action and is
      found to be elevated in high concentrations in the serum of cancer subjects. As
      glycodelin is an angiogenic protein with a potential immunosuppressive role,
      control of LPA synthesis might offer a potential target for intervention.

PMID- 11825668
TI  - Genomic structure of the human beta-PIX gene and its alteration in gastric
      cancer.
AB  - beta-PIX, a newly identified p21-activated kinase (PAK)-interacting exchange
      factors (PIX), encodes a guanine nucleotide exchange factor for Rho guanosine
      triphosphatases. Characterization of beta-PIX gene was performed using the BAC
      Library method. The beta-PIX gene has 17 exons and an A/T polymorphism at the
      32nd base upstream of the intron/exon junction of exon 7. The frequencies of
      genotypes A/T, A/A and T/T were 23.6% (13/55), 72.7% (40/55) and 3.6% (2/55),
      respectively; these frequencies are in Hardy-Weinberg equilibrium. Two out of 14
      informative tumors (14.3%) were shown to have lost their heterozygosity at this
      locus, but no mutations in the remaining alleles were detected. In addition, we
      examined the gene-expression profile in another set of 30 gastric samples, but no
      significant over-expression of either the beta-PIX gene or the alpha-PIX gene was
      found. Though the beta-PIX gene has been speculated to potentially have tumor
      related biological characteristics, the findings of the present study suggest
      that the involvement of beta-PIX gene in human gastric carcinogenesis is minimal.

PMID- 11825669
TI  - Tumor progression, histologic grading and DNA-ploidy as predictive factors of
      lymphogenous metastasis in primary carcinoma of the Fallopian tube.
AB  - The bad prognosis of primary carcinoma of the Fallopian tube (FTC), with 5-year
      overall survival rates of only 35%, is particularly ascribed to lymphogenous
      metastasis. Yet, we know very little on the pathophysiologic factors on which
      this lymphogenous metastasis is based. The present study, therefore, aims at
      evaluating the influence of intra-abdominal tumor progression and tumor-cell
      anaplasia on lymphogenous metastasis in FTC. We studied 41 cases of FTC, who had
      been subjected to radical lymphadenectomy during primary operation in a
      retrospective analysis. Staging was done by International Federation of
      Gynecology and Obstetrics-classification. Histologic grading and nuclear DNA
      content (DNA-index) were used for evaluating tumor-cell anaplasia. Histologic
      grading discriminated between highly differentiated (G1), moderately
      dedifferentiated (G2), and dedifferentiated (G3) tumors. According to their DNA
      indices, tumors were separated into three groups: DNA-index < or =1.1 (euploid
      cases), DNA-indices between 1.1 and 2.0 (cases of intermediate ploidy), and DNA
      index >2.0 (aneuploid cases). The overall incidence of lymph node metastases was
      43.9%. There was no correlation between histologic grading and DNA-index
      (P=0.98). Lymphogenous metastasis set in after the tumor had transgressed the
      tube (intra-abdominal stage II). Further intra-abdominal tumor progression
      (including omentum, liver, or peritoneum) significantly increases the incidence
      of lymph node metastases (P=0.02). There was only a single G1-tumor that had
      already disseminated into the lymph, all other cases of lymph node metastases
      were found in G2- or G3-tumors. DNA-index and the extent of lymphogenous
      metastases were not found to be correlated (P=0.74). CONCLUSIONS: The extent of
      lymphogenous metastases in FTC depends above all on intra-abdominal tumor
      progression. This fact has clinical consequences as the indication for
      lymphadenectomy can be obtained directly during operation. The results of
      histologic grading are of no impact on the surgical proceedings; the
      determination of DNA-ploidy is negligible.

PMID- 11825670
TI  - Increased expression of metabotropic glutamate receptor subtype 1 on
      spinothalamic tract neurons following spinal cord injury in the rat.
AB  - Spinal cord injury (SCI) leads to an increase in metabotropic glutamate receptor
      subtype 1 (mGluR1) immunoreactivity in the peri-lesion area. The increased
      expression of mGluR1 parallels the development of thermal hyperalgesia and
      mechanical allodynia and has been suggested to contribute to the development and
      maintenance of chronic central pain (CCP) syndromes resulting from SCI. However,
      expression of mGluR1 has not been directly shown to increase on cells in the pain
      pathway. Therefore, the expression of mGluR1 on spinothalamic tract (STT) neurons
      was quantified using confocal imaging and densiometric analysis in normal, sham,
      and SCI rats. Contusion SCI produced an increase in mGluR1 expression on STT
      cells in both the cervical enlargement and the spinal section just rostral to
      contusion SCI. These results suggest that mGluR1 is expressed on neurons that
      modulate pain transmission and expression on these cells increases following
      injury, supporting the hypothesis that mGluR1 contributes to CCP following SCI.

PMID- 11825671
TI  - Tea catechin, (-)-epigallocatechin gallate, facilitates cholinergic ganglion
      transmission in the myenteric plexus of the guinea-pig small intestine.
AB  - Intracellular recordings were made from myenteric S neurons of the guinea-pig
      ileum. One of the major tea catechins, (-)-epigallocatechin gallate (EGCG at
      concentrations from 1 to 20 microM), was applied by superfusion to examine its
      effect on cholinergic ganglion transmission in the myenteric plexus. Fast
      excitatory postsynaptic potentials (EPSPs) evoked by electrical stimulation to
      ganglia and/or internodal fiber tracts were augmented in amplitude by EGCG in
      about 60% of tested neurons without changing the postsynaptic sensitivity to
      acetylcholine (ACh) applied by ionophoresis. Furthermore, the amplitude-ratio of
      paired fast EPSPs was increased by EGCG. These results indicated that the site at
      which EGCG augmented the fast EPSPs was presynaptic. It is concluded that EGCG
      can facilitate the cholinergic ganglion transmission possibly by increasing the
      amount of ACh released and, together with its previously described depolarizing
      action on myenteric neurons, may modulate the activity of the myenteric plexus of
      the guinea-pig ileum.

PMID- 11825672
TI  - Human neuronal calcium sensor-1 shows the highest expression level in cerebral
      cortex.
AB  - Neuronal calcium sensors (NCS) are important constituents in the intracellular
      signaling pathways. A novel human gene, NCS-1, was identified in the present
      study. Among the 16 human tissues examined, NCS-1 is expressed most abundantly in
      the brain. Among the brain regions, the expression level of NCS-1 in cerebral
      cortex is the highest, which is about six times higher than the average level of
      the whole brain and a hundred times higher than the spinal cord. In the 12
      different anatomical regions of human brain, the expression level of NCS-1 is
      very high in the temporal lobe, occipital pole, frontal lobe, thalamus, amygdala
      and hippocampus; moderate in cerebellum, putamen, caudate nucleus; low in the
      medulla, substantia nigra and the lowest in corpus callosum. Our results suggest
      that NCS-1 in human brain might be involved in a variety of brain functions such
      as sensory processing, motor control, emotional control, learning and memory.

PMID- 11825673
TI  - Estrogen receptor-alpha and -beta coexist in a subpopulation of sensory neurons
      of female rat dorsal root ganglia.
AB  - Immunoreactivities for estrogen receptor-alpha (ER-alpha) and ER-beta are
      expressed in sensory neurons of the dorsal root ganglia (DRG). It has not been
      established, however, if the two receptor subtypes coexist in the same neuron.
      Double-staining immunohistochemical techniques were used to determine if
      subpopulations of neurons in the lumbosacral DRG exist based on their content of
      ERs. Results indicate that some neurons (approximately 17%) of the L6-S1 DRG
      contain ER-alpha -, some (approximately 23%) contain ER-beta - immunoreactivity
      and some (approximately 5%) express immunoreactivity for both subtypes of the ER.
      These results suggest that many sensory neurons can respond to estrogens, but
      estrogens may produce different morphofunctional effects in different neurons
      based on their expression of ER subtypes.

PMID- 11825674
TI  - Genetic association of an apolipoprotein C-I (APOC1) gene polymorphism with late
      onset Alzheimer's disease.
AB  - Since a deletion/insertion polymorphism in the promoter region of the
      apolipoprotein C-I (APOC1) gene has been reported to be associated with late
      onset Alzheimer's disease (LOAD), we examined the hypothesis in a Korean
      population with 120 LOAD cases and 132 age-matched controls. The frequency of
      APOC1 insertion allele (H2) was significantly increased in LOAD than in controls,
      giving an odds ratio of 3.3 (95% CI 2.0-5.5, P<0.0001). Logistic regression
      analysis revealed that the interaction model between APOE epsilon4 and APOC1 H2
      yielded larger odds ratio than other models including either APOE epsilon4 or
      APOC1 H2 alone. In addition, the association between APOC1 H2 and LOAD remained
      significant after adjustment of the effect of APOE epsilon4 (P=0.036). These
      results support previous observations that the APOC1 might be an additional
      susceptibility gene for LOAD.

PMID- 11825675
TI  - Tedisamil blocks BK-type Ca(2+)-dependent K(+) channels and modulates action
      potentials in rat hippocampal neurons.
AB  - Tedisamil, a bradycardic compound in heart, also acts on K(+) channels in
      neurons. We determined the actions of tedisamil on action potentials in CA1
      pyramidal neurons in hippocampal slices and on BK-type Ca(2+)-activated K(+)
      channel activity in inside-out patches excised from hippocampal neurons. In
      slices, tedisamil (5 microM) attenuated the fast afterhyperpolarization (AHP) and
      prolonged the repolarization phase of the action potential. Additionally, the
      compound induced burst-firing activity and enhanced the slow AHP that follows a
      train of action potentials. The single channel data showed tedisamil actions to
      be consistent with open channel blockade of the BK-type of K(+) channel.
      Together, the results are consistent with the possibility that prolongation of
      the action potential by tedisamil is mediated by a tetraethylammonium-like effect
      of the agent to block BK-type Ca(2+)-activated K(+) channels. The study also
      points to a number of effects that may contribute to the known nervous system
      toxicity induced by tedisamil.

PMID- 11825677
TI  - Expression of capsaicin receptor (VR1) by myelinated primary afferent neurons in
      rats.
AB  - The expression of capsaicin (VR1) receptor by A-fiber primary afferent neurons
      has been investigated by double immunohistochemical staining with VR1 and 200 kD
      neurofilament (NF200; an A-fiber marker) antibodies, and by VR1
      immunohistochemical staining in combination with cholera toxin B subunit (CTB;
      also an A-fiber marker) retrograde tracing. Approximately 30% of the VR1-positive
      dorsal root ganglion (DRG) neurons were NF200-positive. Intra-sciatic nerve
      injection of CTB labeled over 30% of the VR1-positive neurons in the L5 DRG. Size
      frequency distribution analysis revealed that these VR1 and NF200, or VR1 and
      CTB, double-labeled neurons were predominantly small and medium sized. These
      results suggest that capsaicin receptors are likely to be expressed by Adelta
      fiber neurons as well as C-fiber neurons.

PMID- 11825676
TI  - Hypoxic tolerance induction in rat brain slices following 3-nitropropionic acid
      pretreatment as revealed by dynamic changes in glucose metabolism.
AB  - Pretreatment with 3-nitropropionic acid (3-NPA) has been shown to induce
      tolerance to ischemic/hypoxic brain damage. However, regional differences in
      tolerance induction by 3-NPA and the degree to which impaired glucose metabolism
      due to 3-NPA pretreatment itself is directly involved remain unknown. To evaluate
      these issues using dynamic positron autoradiography with [(18)F]2-fluoro-2-deoxy
      D-glucose, the cerebral glucose metabolic rate (CMRglc) was serially measured
      before and after hypoxia-loading in rat brain slices pretreated with 3-NPA.
      CMRglc before hypoxia did not significantly differ between the 3-NPA pretreatment
      group and control group. The 3-NPA-associated recovery of CMRglc after
      reoxygenation was observed in the frontal cortex, hippocampus, and cerebellum,
      but not in the striatum and thalamus. Thus, we demonstrated the induction of
      region-specific hypoxic tolerance after 3-NPA pretreatment using CMRglc
      maintenance as an index of neuronal viability, and it is unlikely that this
      induction is associated with the persistence of impaired glucose metabolism due
      to 3-NPA pretreatment.

PMID- 11825678
TI  - Lateralized organization of the cerebellum in a silent verbal fluency task: a
      functional magnetic resonance imaging study in healthy volunteers.
AB  - Functionally, the cerebellum is not only involved in motor control but is also
      thought to influence higher cognitive function including language. Anatomical
      data would suggest crossed reciprocal connections between the cerebellum and
      higher order cortical association areas. In the following study, one left- and
      one right-handed female volunteer underwent functional magnetic resonance imaging
      in a conventional block design. Regions of activation were detected after
      performance of a silent verbal fluency task inside the scanner. In the right
      handed volunteer we found an activation of the left fronto-parietal cortex and
      the right cerebellar hemisphere, while in the left-handed volunteer the
      activation was seen in the right fronto-parieto-temporal cortex and the left
      cerebellar hemisphere. These initial results demonstrate that cerebellar
      activation is contralateral to the activation of the frontal cortex even under
      conditions of different language dominance. They provide evidence for the
      hypothesis of a lateralized organization of the cerebellum crossed to the
      cerebral hemispheres in supporting higher cognitive function.

PMID- 11825679
TI  - Sympathetic blockade significantly improves cardiovascular alterations
      immediately after spinal cord injury in rats.
AB  - Immediately after an experimental spinal cord injury (SCI) in rats, there is a
      large fall in mean arterial pressure (MAP) and heart rate (HR), followed by an
      abrupt increase in MAP. To better understand the mechanism involved in these
      early cardiovascular alterations, we tested the effect of treatment with
      ganglionic and sympathetic blockers in anesthetized rats subjected to T-5 SCI.
      Fall in MAP was partially diminished by propranolol and pentolinium, while
      increase in MAP was abolished by propranolol and pentolinium. Adrenalectomy did
      not diminish the fall in MAP and HR, however, the increase in MAP was
      significantly reduced. Likewise, propranolol and pentolinium completely abolished
      the effects in HR. These data suggest that the early cardiovascular alterations
      secondary to SCI results from an increased parasympathetic activity and a
      sympathetic withdrawal.

PMID- 11825680
TI  - A left-prefrontal lateralized, sympathetic mechanism directs attention towards
      social threat in humans: evidence from repetitive transcranial magnetic
      stimulation.
AB  - The prioritized processing of threat is suggested to be motivated by anxiety,
      regulated by the parasympatheticus, and biased to the right hemisphere. However,
      according to an anterior dimensional model of negative affect this is unlikely to
      be true when threat is of social origin. Social threat is communicated by the
      angry facial expression, and recent research indicates that prioritized
      processing of angry faces is motivated by anger. Anger is a sympathetically
      dominated emotion, and for its expression and experience, neuroimaging data have
      demonstrated anterior lateralization to the left hemisphere. To scrutinize the
      above diverging statements, suprathreshold low-frequency repetitive transcranial
      magnetic stimulation (rTMS) was applied over the right and the left prefrontal
      cortex (PFC) of ten healthy subjects during 15min continuously, and the
      subsequent effects on sympathetic and parasympathetic activity of the heart, and
      selective attention to angry facial expressions were investigated. Combined rTMS
      neuroimaging studies have shown contralateral excitation after unilateral
      supratheshold low-frequency rTMS, hence the strengthening of contralaterally
      mediated emotion functions. The earlier reported increases in selective attention
      to angry facial expressions after right-PFC rTMS were found to be accompanied by
      and significantly associated with elevations in sympathetic activity. Our data
      suggest that a left-PFC lateralized, sympathetic mechanism directs attention
      towards the angry facial expression.

PMID- 11825681
TI  - Melatonin rhythms in stroke patients.
AB  - Very little is known regarding melatonin's circadian rhythm in stroke patients.
      We compared urinary-sulfatoxymelatonin (6-SMT), its major metabolite, in 11
      extensive cortical and seven deep or lacunar stroke patients on day 3 or 4 and
      day 10 post-stroke. Urinary 6-SMT and creatinine measured every 4 h for 24 h
      starting at 06:00 h significantly fluctuated during the day in both types of
      stroke and did not differ between day 3 or 4 and day 10 post-stroke. However, in
      extensive cortical lesions, a delay in the 6-SMT excretion was observed in the
      first post-stroke days compared to day 10. We conclude that circadian oscillator
      is preserved in extensive cortical as well as in deep and lacunar strokes.
      Extensive cortical stroke might delay the melatonin surge during the first post
      stroke days.

PMID- 11825682
TI  - Spermidine antagonizes the inhibitory effect of huperzine A on [3H]dizocilpine
      (MK-801) binding in synaptic membrane of rat cerebral cortex.
AB  - Huperzine A, a novel cholinesterase inhibitor, was found to inhibit the N-methyl
      D-aspartate (NMDA) receptors in the brain. In this study, the mechanisms of the
      NMDA receptor inhibition were investigated using [3H]dizocilpine (MK-801) binding
      in synaptic membrane of rat cerebral cortex. Changing the concentrations of L
      glutamate and L-glycine did not alter the potency of huperzine A. Spermidine
      caused rightward shift of the concentration-response curve of huperzine A, and
      considerably increased its IC(50) value. Huperzine A did not affect the potency
      of unlabeled (+)-MK-801 in [3H]MK-801 binding. Saturation binding studies reveal
      that huperzine A exerts a negative allosteric modulation on the MK-801 binding
      site within the NMDA receptor-channel. The results suggest that huperzine A is a
      non-competitive antagonist of the NMDA receptors, acting at one of the polyamine
      binding sites.

PMID- 11825683
TI  - Deficits in auditory brainstem pathway encoding of speech sounds in children with
      learning problems.
AB  - Auditory brainstem responses were recorded in normal children (NL) and children
      clinically diagnosed with a learning problem (LP). These responses were recorded
      to both a click stimulus and the formant transition portion of a speech syllable
      /da/. While no latency differences between the NL and LP populations were seen in
      responses to the click stimuli, the syllable /da/ did elicit latency differences
      between these two groups. Deficits in cortical processing of signals in noise
      were seen for those LP subjects with delayed brainstem responses to the /da/, but
      not for LPs with normal brainstem measures. Preliminary findings indicate that
      training may be beneficial to LP subjects with brainstem processing delays.

PMID- 11825684
TI  - Complex modulation of human motor cortex excitability by the specific serotonin
      re-uptake inhibitor sertraline.
AB  - Monoamines are powerful modulators of cortical function. Serotonin has complex
      excitatory and inhibitory effects on animal cortex. Here, the effects of a single
      oral dose (100mg) of the selective serotonin re-uptake inhibitor sertraline on
      human motor cortex excitability were investigated in healthy subjects.
      Transcranial magnetic stimulation was used to test motor threshold, motor evoked
      potential intensity curve, cortical silent period, paired-pulse inhibition and
      facilitation and I-wave facilitation. Sertraline resulted in a steeper intensity
      curve and in depressed paired-pulse facilitation (PPF). All other measures and
      spinal and neuromuscular excitability remained unaffected. The steeper intensity
      curve points to an increased excitability of the cortico-spinal neurone, while
      the depressed PPF suggests an enhanced control of the cortico-spinal neurone by
      inhibitory interneurones. These features may improve the signal-to-noise ratio of
      output cells in human motor cortex.

PMID- 11825685
TI  - Neurons associated with behavioral context errors in the primary and higher-order
      gustatory cortices in the monkey.
AB  - Cue responses of neurons in the taste-related cortex of Japanese macaque monkeys
      were studied during a NaCl-water discrimination GO-NOGO task, to compare the
      correct and incorrect responses. Most neurons produced a steady pattern of
      discharges in response to a given cue at both correct and incorrect responses,
      presumably responding to the physicochemical nature of the cue. Some neurons
      showed the discharge pattern for a certain cue changing to that for another cue
      at task error, presumably representing the subsequent behavioral reaction or
      behavioral context. These neurons were mainly located in the precentral operculum
      and orbitofrontal cortex, and rarely in the primary gustatory area, area G.

PMID- 11825686
TI  - p53, p63 and p73--solos, alliances and feuds among family members.
AB  - p53 controls crucial stress responses that play a major role in preventing
      malignant transformation. Hence, inactivation of p53 is the single most common
      genetic defect in human cancer. With the recent discovery of two close structural
      homologs, p63 en p73, we are getting a broader view of a fascinating gene family
      that links developmental biology with tumor biology. While unique roles are
      apparent for each of these genes, intimate biochemical cross-talk among family
      members suggests a functional network that might influence many different aspects
      of individual gene action. The most interesting part of this family network
      derives from the fact that the p63 and p73 genes are based on the "two-genes-in
      one" idea, encoding both agonist and antagonist in the same open reading frame.
      In this review, we attempt to present an overview of the current status of this
      fast moving field.

PMID- 11825687
TI  - The metastasis gene osteopontin: a candidate target for cancer therapy.
AB  - Malignant tumors are characterized by dysregulated growth control, overcoming of
      replicative senescence, and metastasis formation. Current therapeutic regimens
      mostly exert their effects through inhibition of cell cycle progression, leaving
      two major components of transformation untouched. The cytokine osteopontin is
      essential for the dissemination of various cancers. Past research has implied
      several modes in which osteopontin and its main receptors on tumor cells can be
      suppressed. Osteopontin expression is inhibitable on the levels of gene
      transcription and the RNA message, and the osteopontin protein can be blocked
      with antibodies or synthetic peptides. The osteopontin receptor CD44 has been
      targeted by diverse therapeutic strategies, including cytotoxic and
      immunotherapeutic approaches. The receptor integrin alpha(V)beta(3) contributes
      not only to tumor cell dissemination, but also to angiogenesis and osteolysis in
      bone metastases. Small molecule inhibitors of this receptor are under study as
      drug candidates. Because receptors and cytokine ligands that mediate metastasis
      formation are sparsely expressed in the adult healthy organism and are more
      readily reached by pharmaceuticals than intracellular drug targets they may
      represent a particularly suitable focus for therapeutic intervention.

PMID- 11825688
TI  - Cripto in tumors and embryo development.

PMID- 11825689
TI  - Genome-based analysis of pneumococcal virulence factors: the quest for novel
      vaccine antigens and drug targets.

PMID- 11825690
TI  - Tricorn-like proteases in bacteria.
AB  - The tricorn protease is an archaeal protease that forms massive proteasome-like
      capsids with a hollow chamber. beta-Propeller and PDZ domains are thought to play
      a role in substrate selection. By analysis of predicted proteins from novel
      bacterial genome sequences, we have identified four new bacterial tricorn-like
      proteases, complete with similar beta-propeller, PDZ and catalytic domains. We
      propose various hypotheses as to the function of these domains that can now be
      tested in the laboratory.

PMID- 11825691
TI  - Discovering the sweeping power of point mutations using a GIRAFF.
AB  - In pathogenic bacteria, point and other simple mutations can provide a strong
      selective advantage during the course of a single infection. Our understanding of
      the importance of these randomly occurring mutations has been hampered by a lack
      of technologies allowing mutation scanning on a genomic scale. Here, a novel
      technology is described that makes it possible to scan, in a single Southern blot
      experiment, the sequence identity of genomic regions with a combined length of
      hundreds of kilobases.

PMID- 11825692
TI  - Lost and found.

PMID- 11825706
TI  - The interactions of Bartonella with endothelial cells and erythrocytes.

PMID- 11825711
TI  - The importance of the surface urease of Helicobacter pylori: fact or fiction?

PMID- 11825713
TI  - Where are the pseudogenes in bacterial genomes?
AB  - Most bacterial genomes have very few pseudogenes; notable exceptions include the
      genomes of the intracellular parasites Rickettsia prowazekii and Mycobacterium
      leprae. As DNA can be introduced into microbial genomes in many ways, the compact
      nature of these genomes suggests that the rate of DNA influx is balanced by the
      rate of DNA deletion. We propose that the influx of dangerous genetic elements
      such as transposons and bacteriophages selects for the maintenance of relatively
      high deletion rates in most bacteria; the sheltered lifestyle of intracellular
      parasites removes this threat, leading to reduced deletion rates and larger
      pseudogene loads.

PMID- 11825714
TI  - Molecular mycology: a genetic toolbox for Histoplasma capsulatum.
AB  - Research in medical mycology has traditionally been a mix of exciting biology and
      frustrating genetics, although the excitement has been steadily increasing as
      genetic obstacles have been successfully overcome. Now, a variety of fungal
      pathogens can be studied using molecular techniques derived from classical
      bacterial and yeast genetics, but with selective and strategic adaptations.
      Histoplasma capsulatum is the best-studied of the primary pathogens known as
      'dimorphic' fungi, and tailored molecular genetic strategies are beginning to
      reveal a repertoire of genes and gene products intimately associated with
      pathogenesis.

PMID- 11825715
TI  - Evolutionary genomics of pathogenic bacteria.
AB  - Complete genome sequences are now available for multiple strains of several
      bacterial pathogens and comparative analysis of these sequences is providing
      important insights into the evolution of bacterial virulence. Recently, DNA
      microarray analysis of many strains of several pathogenic species has contributed
      to our understanding of bacterial diversity, evolution and pathogenesis.
      Comparative genomics has shown that pathogens such as Escherichia coli,
      Helicobacter pylori and Staphylococcus aureus contain extensive variation in gene
      content whereas Mycobacterium tuberculosis nucleotide divergence is very limited.
      Overall, these approaches are proving to be a powerful means of exploring
      bacterial diversity, and are providing an important framework for the analysis of
      the evolution of pathogenesis and the development of novel antimicrobial agents.

PMID- 11825716
TI  - Desiccation tolerance: a simple process?
AB  - Water is essential for life, and thus the removal of water from a cell is a
      severe, often lethal stress. This is not a remarkable observation but it is one
      that is often taken for granted. Desiccation-tolerant cells implement structural,
      physiological and molecular mechanisms to survive severe water deficit. These
      mechanisms, and the components and pathways which facilitate them, are poorly
      understood. Here, recent developments are considered to illustrate the importance
      of desiccation, longevity and cell stasis in basic microbiology, and the
      relevance of the topic to the metabolic engineering of sensitive cells, including
      those of humans.

PMID- 11825717
TI  - Reoviruses and the host cell.
AB  - Reovirus infection of target cells can perturb cell cycle regulation and induce
      apoptosis. Differences in the capacity of reovirus strains to induce cell cycle
      arrest at G1 and G2/M have been mapped to the viral S1 genome segment, which also
      determines differences in the ability of reovirus strains to induce apoptosis and
      to activate specific mitogen-activated protein kinase (MAPK) cascades
      selectively. Reovirus-induced apoptosis involves members of the tumor necrosis
      factor (TNF) superfamily of death receptors and is associated with activation of
      both death receptor- and mitochondrial-associated caspases. Reovirus infection is
      also associated with the activation of a variety of transcription factors,
      including nuclear factor (NF)-kappaB. Junctional adhesion molecule (JAM) has
      recently been identified as a novel reovirus receptor. Reovirus binding to JAM
      appears to be required for induction of apoptosis and activation of NF-kappaB,
      although the precise cellular pathways involved have not yet been identified.

PMID- 11825720
TI  - The adventure of cardiac surgery.

PMID- 11825721
TI  - Staged carotid and coronary surgery for concomitant carotid and coronary artery
      disease.
AB  - OBJECTIVE: To demonstrate that staged, consecutive, carotid endarterectomy (CEA)
      and coronary artery bypass grafting (CABG) are safe, perhaps preferable,
      alternative for the treatment of patients with severe carotid and coronary artery
      disease. METHODS: During an 8-year period ending December 1999, 77 (2.1%) of 3633
      consecutive patients who were referred for isolated coronary surgery were found
      to have significant carotid disease and underwent CEA, and subsequently, CABG.
      The mean age was 65.2 +/- 5.9 years and 66 (85.7%) were males. The majority
      (84.4%) had triple vessel and 19.4% had left main disease. Carotid disease was
      unilateral in 71 patients (92.2%) and bilateral in six (7.8%), and 57 (74.0%)
      were neurologically asymptomatic. Only obstructions >70% were considered for
      endarterectomy. RESULTS: Eighty-three isolated CEAs were performed with direct
      clamping of the artery (mean 20.1 +/- 5.9 min) in all but one. There were no
      deaths. There were two strokes (2.4%) and three (3.6%) myocardial infarctions
      (MI). The mean admission time was 6.0 +/- 3.5 days. The staging interval was 32.4
      days. During coronary surgery, a mean of 2.9 coronary grafts/patient was
      performed and all but one patient received at least one IMA graft. One patient
      (1.3%) died. There were two cases (2.6%) of MI and three patients (3.9%) had a
      stroke. Hence, the overall rates of perioperative mortality, MI and stroke were
      1.3, 6.3 and 6.3%, respectively. The mean admission time was 8.3 +/- 6.0 days.
      CONCLUSIONS: Staging of carotid and coronary operations resulted in low global
      perioperative mortality and morbidity rates in these high-risk patients and is a
      good alternative therapeutic option.

PMID- 11825722
TI  - Determinants of operative mortality following primary coronary artery bypass
      surgery.
AB  - BACKGROUND: The purpose of this study was to determine the factors which can help
      to predict operative mortality before performing the operation, and afterwards.
      METHODS: The study population consisted of 504 patients (91 women and 413 men)
      who underwent primary isolated coronary artery bypass surgery from December 1997
      to September 1999 by the same surgeon in a referral center in Tehran, Iran.
      Perioperative data were gathered and analyzed both in a univariate and
      multivariate model. RESULTS: After the operation patients spent 7.3 +/- 4.0 days
      in hospital. The total operative morbidity was 20.5%. Arrhythmias were the most
      common complication, with atrial fibrillation as the predominant feature. Major
      complications of the operation were: low cardiac output (4.2%); prolonged
      ventilatory support (2.4%); hemorrhage and exploratory reoperation (2.0%);
      postoperative myocardial infarction (1.4%); postoperative renal failure in
      (1.4%); and postoperative cerebrovascular accident (0.8%). Operative mortality
      rate in this study was 2.98%. Factors associated with high operative mortality in
      univariate analysis were: recent myocardial infarction, low ejection fraction,
      non-elective operation, left main coronary artery disease and prolonged
      cardiopulmonary bypass time. CONCLUSION: Our data suggest that prior to
      operation, operative mortality can be best predicted by urgency of operation and
      left ventricle ejection fraction. After performing the operation, prognostic
      factors include preoperative LVEF < or = 35%, non-elective operation, and
      prolonged cardiopulmonary bypass time. Further study is required to assess the
      generalization of our findings to Iranian patients.

PMID- 11825723
TI  - Off pump coronary artery bypass grafting in EuroSCORE high and low risk patients.
AB  - OBJECTIVE: Off pump coronary artery bypass grafting (OPCAB) is claimed to reduce
      the operative morbidity and mortality in high risk patients. It was the aim of
      the study to compare the outcome of OPCAB patients classified as high- and low
      risk according to the EuroSCORE. METHODS: Medical records of patients undergoing
      off pump coronary artery bypass grafting (n=126) at our institution between 1998
      and 2001 were retrospectively reviewed. We classified them into two subgroups:
      low risk (EuroSCORE < or = 5, n=72, male 58 (81%), female 14 (19%), age 61 (37
      78) years) and high risk (EuroSCORE >5, n=54, male 32 (59%), female 22 (41%), age
      73 (42-83) years). RESULTS: EuroSCORE high risk patients showed significantly
      higher rates of blood transfusion (70 vs 31%; P<0.0001), intraaortic balloon pump
      insertion (16 vs 3%; P=0.013), atrial fibrillation (43 vs 22%; P=0.014), and
      renal failure (13 vs 3%; P=0.028). ICU length of stay was significantly longer in
      the high risk group (25 vs 22 h; P=0.002). There was also a higher perioperative
      mortality in the high risk group (9 vs 0%; P=0.008). CONCLUSION: From these data
      we conclude that using off pump coronary artery bypass grafting results as
      predicted by the EuroSCORE can be achieved. OPCAB is safe for low risk patients.
      Major complications seem to occur preferentially in the high risk group.

PMID- 11825724
TI  - Inaccuracy of four coronary surgery risk-adjusted models to predict mortality in
      individual patients.
AB  - OBJECTIVES: This study was undertaken to evaluate the accuracy of four different
      risk-adjusted models in predicting mortality in individual patients who are
      undergoing coronary artery by-pass graft surgery. In the last decade several
      models to stratify patients before open heart surgery, according to factors
      affecting mortality, were developed with the aim of retrospectively comparing
      outcomes of open heart surgery, based on reliable stratification of case-mix, and
      of prospectively identifying high risk patients as a basis for a meaningful
      informed consent for patients counseling. METHODS: The pre-operative risk of
      death was calculated with four different models in 418 consecutive patients who
      underwent coronary artery by-pass surgery and then compared with the actual
      outcome. To discriminate patients with favorable and unfavorable outcome, the
      logistic regression analysis and the areas under the receiver-operating
      characteristic curves were applied. The accuracy score was used to evaluate the
      reliability of each score to predict the individual outcome. RESULTS: Seven
      deaths (1.7%) were observed within 30 days from the operation, and the overall
      incidence was similar to that predicted by all models. Only the NBI score was not
      able to discriminate survivors from patients who will die, and the areas under
      the curves were 0.596 for the Parsonnet score, 0.861 for the Cleveland Clinic
      Foundation score, 0.823 for the French score, and 0.806 for the EuroSCORE. The
      four models were highly accurate (between 0.97 and 0.98) to predict the overall
      mortality. In seven patients who died the mean predictive scores were very low
      and ranged between 2.1 and 4.6, but were significantly higher than those of
      patients who survived (between 1.1 and 2.2). CONCLUSIONS: The four pre-surgical
      predictive models were similarly able to discriminate favorable vs. unfavorable
      outcomes and highly accurate to predict overall mortality, but very inaccurate to
      predict mortality in individual patients.

PMID- 11825725
TI  - Changing profile of patients undergoing redo-coronary artery surgery.
AB  - OBJECTIVE: To outline the changes of the patient population undergoing redo
      coronary artery bypass surgery (RECABG). METHODS: Preoperative data of 582 first
      RECABGs, January 1987-June 2000 were analyzed. Group A: 1987-1991 (n=193); group
      B: 1992-1995 (n=201); and group C: 1996-June 2000 (n=188). RESULTS: These 582
      RECABGs represent about 8.5% of the performed bypass surgeries during this
      period. Mean age (P=<0.001), percentage of patients with kidney disease
      (P=0.001), a preoperative PTCA (P<0.001) increased. Significant more elective
      operations (P<0.001) and lesser urgent operations (P=0.001) were performed in
      group C. There is a significant different distribution of vessel disease over the
      three periods (P=0.04). Significant more patients had a patent IMA graft
      (P<0.001). The angina-free period after CABG (P<0.001), the time period between
      both operations (P<0.001) and the period between the new onset of angina and the
      RECABG (P=0.012) increased significantly. Despite the importance of progression
      of atherosclerosis of any sort decrease significantly (P<0.001) over the whole
      study, there is a significant increase of patients reoperated for isolated
      progression of the disease in the native coronary arteries (P<0.001) in group C.
      The impact of late GF was not different for the total group (P=0.82), however,
      the percentage of RECABGs for isolated late GF increased significantly between
      group A and B (P<0.001) but there was a decrease from B to C, however, not
      significant (P=0.067). CONCLUSION: During the past few years there is a trend in
      RECABG of older patients, with more coexisting diseases. There are an increasing
      number of patients with patent arterial grafts, an increase of the event-free
      period after the CABG, the period between the CABG and RECABG and of the time
      period between the onset of new angina and the RECABG. Although the impact of
      atherosclerosis, as angiographic indication, decreased over the total group,
      there is the significant increase of the percentage of patients reoperated
      because of isolated progression of atherosclerosis in the native coronary
      arteries.

PMID- 11825726
TI  - Perivenous application of fibrin glue reduces early injury to the human saphenous
      vein graft wall in an ex vivo model.
AB  - OBJECTIVES: From animal and clinical studies it is known that prevention of 'over
      distention' of vein grafts by using extravascular support ameliorates the
      arterialization process in vein grafts with subsequent more favorable patency.
      The most ideal support is a biodegradable, porous, elastic graft (Biomaterials,
      15 (1994) 83). However, a specific graft meeting these criteria is not available
      yet. Fibrin glue on the other hand, although used for other purposes in cardiac
      surgery, theoretically meets the criteria for ideal extravascular support. In
      this ex vivo study, we evaluated the possible beneficial effect of perivenous
      application of fibrin glue. METHODS: Segments of human vein graft obtained during
      CABG procedures in 14 consecutive patients were placed in a side loop of the
      extracorporeal perfusion circuit. In this way the study vein grafts did meet
      identical circumstances as the vein grafts implanted. Perfusion in the loop was
      started with a flow just enough to counteract the collapse of the vein, usually
      about 8 mm Hg, and alternately around the segments fibrin glue was applied or no
      perivenous support was administered as control. After 1 min of soldification,
      perfusion was started with a pressure of about 60 mm Hg (non-pulsatile flow).
      Perfusion was maintained for 60 min, after which the grafts were collected for
      light microscopic and electron microscopic assessment. RESULTS: Light microscopy
      and electron microscopy showed remarkable attenuation of endothelial cell loss
      and less injury of smooth muscle cells of the circular muscle layer of the media
      in the fibrin glue supported vein grafts compared to the non-supported group.
      CONCLUSION: Fibrin glue is able to accomplish adequate external vein graft
      support, preventing overdistention, in an ex vivo model. This provides a basis
      for clinical application. Further investigation is necessary to evaluate long
      term effects.

PMID- 11825727
TI  - Plasma levels and vascular effects of endothelin and big endothelin in patients
      with stable and unstable angina pectoris undergoing coronary bypass grafting.
AB  - OBJECTIVES: The aim of this study was to determine the plasma and pericardial
      levels of endothelin-1 (ET-1) and its precursor big endothelin-1 (Big ET-1) in
      patients with unstable and stable angina prior to and following coronary bypass
      surgery. To further investigate the content of ET-1, tissue levels were studied
      in the internal mammary artery (IMA) in patients with stable and unstable angina
      pectoris. Finally, the difference in reactivity of the IMA to ET-1 and Big ET-1
      in stable and unstable patients was evaluated. METHODS: Plasma and pericardial
      levels of ET-1 and Big ET-1 were determined with radioimmunoassay in 81 patients
      (33 unstable) immediately before coronary bypass surgery, and at 6, 14, 40 and 64
      h following the procedure. Specimens of the distal IMA from 12 patients (six
      unstable) were collected at the beginning of surgery for determination of tissue
      levels of ET-1. Additionally, distal internal mammary arteries were obtained from
      another 24 patients (12 unstable). These vessels were mounted in organ baths for
      functional studies on vascular reactivity to ET-1 and Big ET-1. RESULTS: The
      peripheral plasma levels of ET-1 in unstable patients were significantly lower in
      patients with unstable angina compared with patients with stable angina pectoris
      at all points of measurement. The levels of Big ET-1 were significantly higher
      pre-operatively in the unstable group, but decreased to similar levels to those
      of stable patients following coronary bypass grafting. There was no difference in
      ET-1 tissue content in the IMA between the patients. ET-1 and Big ET-1 caused an
      endothelin(A) (ET(A))-receptor blocker sensitive, concentration-dependent
      contraction of the IMA obtained from stable as well as unstable patients.
      CONCLUSIONS: It is concluded that unstable angina pectoris is associated with an
      increased ET-1 turnover. This increased turnover may participate in the local
      regulation of coronary vascular tone with subsequent influence of the condition
      of the patients. The present investigation also implies that ET(A)-blockade may
      be useful as an additional pharmacological principal in the treatment of unstable
      angina pectoris prior to revascularization, as well as to prevent post-operative
      arterial graft spasm.

PMID- 11825728
TI  - Diltiazem during reperfusion preserves high energy phosphates by protection of
      mitochondrial integrity.
AB  - OBJECTIVE: This study evaluates the effects of diltiazem administered during
      reperfusion on hemodynamic, metabolic, and ultrastructural postischemic outcome.
      METHODS: Hearts of 38 adult White New Zealand rabbits underwent 60 min of global
      cold ischemia followed by 40 min of reperfusion in an erythrocyte perfused
      isolated working heart model. Hearts were randomly assigned to four groups and
      received diltiazem (0.1, 0.25, and 0.5 micromol/l) during reperfusion only, or
      served as control. RESULTS: The postischemic time courses of heart rate, aortic
      flow, and external stroke work clearly reflected the dose-dependent negative
      chronotropic and inotropic efficacy of diltiazem in the two higher
      concentrations. High energy phosphates (HEP) determined from myocardial biopsies
      taken after 40 min of reperfusion were significantly better preserved in all
      treatment groups compared to control hearts. Similarly ultrastructural grading of
      mitochondria and myofilaments revealed a significant reduction of reperfusion
      injury in hearts that received diltiazem compared to control. CONCLUSIONS:
      Diltiazem protects mitochondrial integrity and function, thereby preserving
      myocardial HEP levels. Only low dose diltiazem (0.1 micromol/l) during
      reperfusion combines both, optimal mitochondrial preservation with minimal
      changes in hemodynamics.

PMID- 11825729
TI  - Cardiopulmonary bypass induced inflammation: pathophysiology and treatment. An
      update.
AB  - Cardiac surgery with cardiopulmonary bypass (CPB) induces an acute phase reaction
      that has been implicated in the pathogenesis of several postoperative
      complications. Recent data indicate that a complex sequence of events leads to
      the final activation of leukocytes and endothelial cells (EC), which is
      responsible for cell dysfunction in different organs. Activation of the contact
      system, endotoxemia, ischemia and reperfusion injury and surgical trauma are all
      potential triggers of inflammation following CPB. Different pro- and anti
      inflammatory mediators (cytokines, adhesion molecules) are involved and their
      release is mediated by intracellular transcription factors (nuclear factor-kappa
      B, NF-kappa B). In this review, we examine recent advances in the understanding
      of the pathophysiology of the CPB-induced acute phase reaction and evaluate the
      different pharmacological, technical and surgical strategies used to reduce its
      effects. Emphasis is given to the central role of transcription factor NF-kappa B
      in the complex mechanism of the inflammatory reaction and to the effects of
      compounds such as heparin and glycosaminoglycans, phosphodiesterase inhibitors
      and protease inhibitors whose role as anti-inflammatory agent has only recently
      been recognized.

PMID- 11825730
TI  - Intracardiac ultrasonic suture welding for knotless mitral valve replacement.
AB  - OBJECTIVE: The difficulty in tying multiple knots with endoscopic instruments
      constitutes a technical obstacle to the development of closed-chest valve
      surgery. The following set of experiments was undertaken to ascertain the in-vivo
      feasibility of using an intracardiac ultrasonic welding device for knotless
      suture fixation during mitral valve replacement (MVR). METHODS: Five adult sheep
      weighing 48-52 kg underwent MVR with a commercially available mechanical
      prosthesis, using pledgetted interrupted polypropylene sutures. An ultrasonic
      suture welder designed for intracardiac use was used to adjust suture tension and
      fuse strands together without knots. Echocardiographic assessment of the mitral
      prosthesis was carried out at baseline and after maintenance of supraphysiologic
      arterial pressures for 60 min. Subsequently, the animals' explanted hearts were
      assessed under sustained left ventricular (LV) pressurization to 180 mmHg in an
      ex-vivo pressure-loop system. RESULTS: MVR was successfully performed in all
      animals and welds reliably completed in less than 1 s. One sheep could not
      successfully be weaned off cardiopulmonary bypass; however, a normal prosthetic
      valve implant was confirmed at post-mortem examination. Echocardiographic
      assessment prior to and during LV pressurization revealed normal seating and
      function of the prosthesis in all cases. At post-mortem examination all valves
      were adequately implanted, suture tails laid flat on the surface of the
      prosthesis' sewing ring, welded suture strands were intact and accurately point
      fused together, and no evidence of perivalvular leak was found around any of the
      prostheses despite sustained LV pressurization. CONCLUSIONS: This new modality
      proved reliable in an acute sheep model of MVR and could constitute a promising
      avenue towards facilitation of total endoscopic valve procedures in humans.

PMID- 11825731
TI  - Evaluation of clinical treatment of atrial fibrillation associated with rheumatic
      mitral valve disease by radiofrequency ablation.
AB  - OBJECTIVES: The aim of this clinical study was to evaluate the effectiveness and
      advantages of the radiofrequency ablation maze procedure in the treatment of
      atrial fibrillation associated with rheumatic mitral valve disease. METHODS: We
      developed one kind of modified Cox III maze procedure with the use of
      radiofrequency ablation in the treatment of atrial fibrillation associated with
      rheumatic mitral valve disease and compared the outcome of 96 patients of atrial
      fibrillation associated rheumatic mitral valve disease who underwent
      radiofrequency ablation maze procedure plus mitral valve replacement with that of
      87 patients with atrial fibrillation associated rheumatic mitral valve disease
      who had mitral valve replacement during the same interval by the same surgeon.
      The patients in the two groups were similar in age, gender, preoperative New York
      Heart Association class and duration of preoperative atrial fibrillation.
      RESULTS: No operative deaths occurred in the study group and the control group.
      Duration of cardiopulmonary bypass (137.63 +/- 10.82 vs. 90.95 +/- 7.65 min,
      P<0.01) and duration of aortic crossclamping (56.96 +/- 6.19 vs. 32.66 +/- 3.55
      min, P<0.01) were prolonged in the study group. Blood loss from chest tubes was
      similar in the two groups (494.06 +/- 100.44 vs. 476.09 +/- 115.84 ml, P=0.263).
      Freedom from atrial fibrillation in the study group was 77% 3 years after the
      operation compared with 25% in the control group (P<0.01). CONCLUSIONS: The
      addition of the radiofrequency ablation maze procedure to mitral valve
      replacement is safe and effective in the treatment of atrial fibrillation
      associated with rheumatic mitral valve disease.

PMID- 11825732
TI  - Impact of junctional ectopic tachycardia on postoperative morbidity following
      repair of congenital heart defects.
AB  - OBJECTIVE: To determine the incidence of postoperative junctional ectopic
      tachycardia (JET), we reviewed 343 consecutive patients undergoing surgery
      between 1997 and 1999. The impact of this arrhythmia on in-hospital morbidity and
      our protocol for treatment were assessed. METHODS: We reviewed the postoperative
      course of patients undergoing surgery for ventricular septal defect (VSD; n=161),
      tetralogy of Fallot (TOF; n=114), atrioventricular septal defect (AVSD; n=58) and
      common arterial trunk (n=10). All patients with JET received treatment, in a
      stepwise manner, beginning with surface cooling, continuous intravenous
      amiodarone, and/or atrial pacing if the haemodynamics proved unstable. A linear
      regression model assessed the effect of these treatments upon hours of mechanical
      ventilation, and stay on the cardiac intensive care unit (CICU). RESULTS: Overall
      mortality was 2.9% (n=10), with three of these patients having JET and TOF. JET
      occurred in 37 patients (10.8%), most frequently after TOF repair (21.9%),
      followed by AVSD (10.3%), VSD (3.7%), and with no occurrence after repair of
      common arterial trunk. Mean ventilation time increased from 83 to 187 h amongst
      patients without and with JET patients (P<0.0001). Accordingly, CICU stay
      increased from 107 to 210 h when JET occurred (P<0.0001). Surface cooling was
      associated with a prolongation of ventilation and CICU stay, by 74 and 81 h,
      respectively (P<0.02; P<0.02). Amiodarone prolonged ventilation and CICU stay,
      respectively, by 274 and 275 h (P<0.05; P<0.06). CONCLUSIONS: Postoperative JET
      adds considerably to morbidity after congenital cardiac surgery, and is
      particularly frequent after TOF repair. Aggressive treatment with cooling and/or
      amiodarone is mandatory, but correlates with increased mechanical ventilation
      time and CICU stay. Better understanding of the mechanism underlying JET is
      required to achieve prevention, faster arrhythmic conversion, and reduction of
      associated in-hospital morbidity.

PMID- 11825733
TI  - Surgical management of acute aortic root endocarditis with viable homograft: 13
      year experience.
AB  - OBJECTIVE: Cryopreserved homograft valves have been used for acute infective
      aortic root endocarditis with great success but it is compounded by its
      availability in all sizes. The long-term clinical results of geometric mismatched
      homografts are not well defined and addressed. METHODS: Over a 15-year period
      (April 1986-June 2001), 816 patients presented with active infective
      endocarditis. One hundred and eighty-two of the patients aged between 9 and 78
      years (mean: 51.0 +/- 1.13 years) consisting of 142 males and 40 females received
      homograft aortic valves. One hundred and ten patients were in NYHA functional
      class III and 72 in class IV and in cardiogenic shock. Of the patients, 2.7%
      suffered from septic embolism. One hundred and twenty-four (68.1%) patients
      presented with periannular abscesses and 58 (31.9%) with no abscess while 107
      native valve (NVE) and 75 prosthetic valve (PVE) endocarditis were diagnosed
      preoperatively by transesophageal echocardiography (TEE) and confirmed
      intraoperatively. Freehand subcoronary implantation (FSCI) was used in 106
      patients and root replacement in 76 patients. RESULTS: The operative death was
      8.5% and for patients in NYHA functional class IV and in cardiogenic shock was
      14.5%. Late mortality rate was 7.9%. Patient survival after discharge from
      hospital at 1 year was 97% and at 10 years was 91%, respectively. Thirty-one
      (22.1%) patients underwent reoperation after 1.7 years (mean) with two deaths
      (6.4%). Early (< or = 60 days) and late reinfection rate was 2.7 and 3.6%,
      respectively. Freedom from reoperation for matched and undersized homografts at
      10-13 years was 85 and 55%, respectively. The univariate model identified
      undersized homograft (P=0.002), FSCI (P=0.09) and reinfection (P=0.0001) as
      independent risk factors for developing early and late valve dysfunction
      resulting in reoperation and homograft explant. CONCLUSION: Early aggressive
      valve replacement with homograft for active infective aortic root endocarditis
      with periannular abscesses is more successful than delayed last resort surgery.
      Homografts exhibit excellent clinical performance and durability with a low rate
      of reinfection, if properly inserted. Undersized homograft is an incremental risk
      factor for early and late reoperation.

PMID- 11825734
TI  - Aortic and pulmonary root: are their dynamics similar?
AB  - OBJECTIVES: The long-term behavior of the pulmonary autograft in the aortic
      position (Ross procedure) remains uncertain. Using three-dimensional (3D)
      sonomicrometry (200 Hz) we compared the dynamics of the aortic and pulmonary
      roots. METHODS: Twenty-four crystals were implanted in each aortic (eight sheep)
      and pulmonary roots (six sheep) at: base (3 x 2), commissures (3 x 2),
      sinotubular junction (3 x 2), ascending aorta (3) and pulmonary trunk (3). Under
      stable hemodynamic conditions, geometric changes were time-related to left
      ventricular pressure (LV) and aortic pressure. RESULTS: The expansion of the
      aortic root is twice that of the pulmonary root. During the cardiac cycle, the
      aortic root volume increased by 37.7 +/- 2.7% (mean +/- SEM) versus 20.9 +/- 1.0%
      for the pulmonary root. Both were cone-shaped at end diastole. Because expansion
      at commissures was twice that of the base, both roots became more cylindrical
      during ejection. Although both roots started to expand prior to ejection and
      reached maximal expansion during the first third of ejection, the commissural and
      sinotubular junction dynamics were different in each root. While in the aortic
      root, expansion at commissural and sinotubular junction levels was significantly
      different (63.7 +/- 3.6% versus 37.0 +/- 2.1%), in the pulmonary root, they were
      similar (29.0 +/- 1.3% versus 27.7 +/- 1.4%). Expansion of the three sinuses was
      also different (P<0.001). In the aortic root: the right expanded more than the
      left and more than the non-coronary sinus. In the pulmonary root: the right sinus
      expanded more than the anterior more than the left. CONCLUSIONS: Dynamic
      differences might explain the global pulmonary root dilatation when subjected to
      systemic pressure, particularly at the level of the sinotubular junction which
      might result in the autograft failure. Differences in the asymmetrical expansion
      of the aortic and pulmonary roots should be considered for the implantation of
      the pulmonary autograft in the most physiological position.

PMID- 11825735
TI  - The elephant trunk technique: operative results in 100 consecutive patients.
AB  - OBJECTIVES: To describe morbidity and mortality in patients undergoing the
      elephant trunk (ET) implantation as the first stage in the repair of their mega
      aorta and to assess determinants for the occurrence of complications. METHODS:
      One hundred consecutive patients undergoing an ET implantation between 1984 and
      June 2001 were retrospectively analyzed. The ET was implanted as an extension of
      an isolated aortic arch (1%), an aortic valve replacement+ascending aorta+arch
      (14%), a root replacement+ascending aorta+arch (37%) and an ascending aorta+arch
      (48%). Indications for surgery were acute aortic dissection (1%), an inflammatory
      aneurysm (3%), chronic post-dissection (31%) or degenerative (65%) aneurysm.
      Marfan syndrome was present in six patients. For cerebral protection, we used
      isolated deep hypothermic circulatory arrest (7%), deep hypothermic circulatory
      arrest combined with uni- or bilateral antegrade cerebral perfusion (18%) or
      isolated uni- or bilateral antegrade cerebral perfusion (75%). Uni- and
      multivariate analysis was used. RESULTS: There were no intraoperative deaths.
      Hospital mortality was 8%. The causes of death were cardiac in one, rupture of a
      remote aneurysm in three, tamponade in one and sepsis in three. After
      multivariate analysis, no single factor emerged as a risk factor for hospital
      mortality. Permanent and transient neurologic dysfunction occurred in 4 and 2%,
      respectively. Univariate analysis showed the operative period before 1990
      (P=0.029) and emergency (P=0.018) as significant factors for postoperative
      neurologic dysfunction; after stepwise logistic regression analysis, only
      emergent operation retained significance (P=0.005). Permanent hoarseness, total
      atrioventricular block requiring pacemaker implantation and re-thoracotomy for
      bleeding occurred in 17, 2 and 30%, respectively. CONCLUSIONS: The first step in
      the repair of a mega aorta, the implantation of an ET, can be performed with a
      low mortality and an acceptable morbidity. The risk of central neurologic damage
      is higher in emergency interventions.

PMID- 11825736
TI  - Surgical treatment of acute traumatic rupture of the thoracic aorta a timing
      reappraisal?
AB  - OBJECTIVE: To report our experience with surgery of thoracic aortic rupture due
      to blunt trauma. METHODS: Between October 1976 and October 1999, 50 patients
      suffering from acute rupture of the thoracic aorta due to blunt trauma were
      operated on. On admission, 22 patients (44%) presented with hypovolemic shock and
      all but five (90%) sustained major associated injuries. Thirty-one patients (62%)
      underwent immediate operation for aortic repair, whereas the procedure was
      delayed from 6 to 60 days in ten patients because of late diagnosis or coexisting
      life-threatening lesions thought to largely worsen the operative risk. In 48
      patients, the aortic repair was carried out with the aid of cardiopulmonary
      bypass (CPB) in order to maintain the distal perfusion and to prevent spinal cord
      injury. An inert 'Gott' shunt and the 'clamp-and-sew' technique were used in one
      patient each. RESULTS: The hospital mortality amounts to 18% (nine patients).
      Four patients (8%) died intraoperatively and five patients (10%) died in the
      postoperative course. In five patients (10%) death was caused by cerebral or
      pulmonary hemorrhage, possibly worsened by systemic heparinization during CPB.
      One case of postoperative paraplegia (2%) was observed in a patient operated on
      with the aid of CPB. There was neither aortic rupture nor sudden death in the
      group of patients in whom the surgical procedure was delayed. CONCLUSIONS: The
      immediate outcome of patients suffering from acute traumatic aortic rupture
      strongly depends on the associated injuries. In some cases, the emergency aortic
      repair must be favorably delayed because of the necessity of life-sustaining
      measures and management of major coexisting injuries, which could be worsened by
      the use of CPB. Conversely, the risk of paraplegia is significantly reduced by
      the use of CPB and distal perfusion during the time of aortic cross-clamping.

PMID- 11825737
TI  - The mechanism of injury in blunt traumatic rupture of the aorta.
AB  - Rupture of the aorta accounts for a significant proportion of fatalities
      following blunt trauma. A great deal of consensus exists describing the
      circumstances under which acute traumatic aortic dissection occurs as well as its
      investigation and management. However, there remains some controversy surrounding
      the pathogenic aetiology underlying this injury. Univariate and multivariate
      models of blunt traumatic aortic rupture (BTAR) are discussed. To account for the
      consistency in the nature of BTAR, despite a range of trauma scenarios, the
      concepts of dynamic multivariate models and a final common pathway are
      introduced. Clinical management is described elsewhere. Greater understanding of
      the mechanism of BTAR could lead to a range of safety systems aimed at a
      reduction in its incidence and severity.

PMID- 11825738
TI  - Long term results of diaphragmatic plication for unilateral diaphragm paralysis.
AB  - OBJECTIVES: To examine whether diaphragmatic plication is an effective and
      lasting treatment option for non-malignant diaphragmatic paralysis. METHODS:
      Nineteen patients who had undergone diaphragm plication (1983-1990) were recalled
      for interview, pulmonary function testing and chest X-ray. RESULTS: There were 13
      men and six women aged 24-73 (mean 55). Diaphragm paralysis was idiopathic (n=9),
      postsurgical (n=3), related to cervical spondylosis (n=4) and neck injury (n=2).
      Patients presented with breathlessness (18/19) or orthopnoea (1/19). Symptoms had
      lasted 3-60 months (mean 24 months). All patients had a raised hemidiaphragm on
      chest X-ray with paradoxical movement on ultrasound. Mean preoperative FVC was
      71% predicted (range 38-93, SD 12.9) and mean FEV(1) was 67% predicted (range 33
      90, SD 10.8). Supine lung volumes were 81% (mean) of sitting values. There were
      six right plications and 13 left. There were no postoperative deaths. One patient
      required re-plication. Follow-up (18/19 of original operated patients) ranged
      from 7-14 years (mean 10 years). Three patients had died of unrelated causes and
      one patient failed to attend long term follow-up, leaving 15 patients of the
      original 19 operated on. Positional change in lung volumes was not affected by
      surgery at early (6 week) or late (>5 year) follow-up. FVC, FEV(1), FRC and TLC
      improved by 10.1*, 11.8*, 16.9* and 9.2*%, respectively, at early follow-up and
      11.8*, 15.4*, 26 and 13.3*% at late follow-up (*P<0.005 signed rank). Dyspnoea
      scores at long term follow-up improved 1 point (n=5), 2 points (n=5) and 3 points
      (n=2), remained unchanged (n=1) or dropped 1 point (n=2). Of the 15 patients
      followed up all but one who had been employed returned to work. 14/15 patients
      expressed satisfaction with their surgery. CONCLUSION: Diaphragm plication is an
      effective procedure with lasting results.

PMID- 11825739
TI  - Preliminary findings in the neurophysiological assessment of intercostal nerve
      injury during thoracotomy.
AB  - OBJECTIVE: Previous work has suggested that intercostal nerve injury is a major
      factor in the aetiology of chronic post-thoracotomy pain. The aim of this study
      was to establish if there was identifiable intercostal nerve injury during
      thoracotomy. METHODS: Intercostal nerves were stimulated and motor evoked
      potentials were recorded from intercostal muscles in 13 patients undergoing
      thoracotomy. Measurements were taken before and after entering the pleural space,
      after removal of the rib retractor and after intercostal space closure. RESULTS:
      Intercostal nerves functioned normally before and after entering the pleural
      space. After the rib retractor was removed, there was a total conduction block in
      the nerve immediately above the incision in every patient. In the nerves above
      this, six had a total block, one a partial block and three had normal conduction.
      There was a total conduction block in the nerve immediately below the incision in
      all but one patient. Of the nerves below this, four had a total block, two a
      partial block and three had normal conduction. In the cases of total conduction
      block, there was either a discrete block at the level of the distal end of the
      rib retractor or impairment throughout the whole nerve. Intercostal space closure
      did not injure any previously uninjured nerve. In a solitary patient where rib
      retraction was not employed, there was no impairment of the intercostal nerves
      throughout the operation. CONCLUSIONS: This study demonstrates for the first time
      that intercostal nerve injury occurs routinely due to rib retraction during
      thoracotomy. We believe that it may be an important step toward understanding the
      cause of post-thoracotomy neuralgia.

PMID- 11825741
TI  - Prognostic factors in thymic epithelial neoplasms.
AB  - OBJECTIVES: The primary thymic epithelial neoplasms (PTENs) are uncommon tumours
      with a broad spectrum of both biological and morphological features. The aim of
      this study is to analyse the prognostic factors that influence survival. METHODS:
      Forty-four patients with a complete follow-up were analysed. Nine patients
      (20.5%) were asymptomatic, the most common symptoms in the rest being myasthenia
      gravis and dyspnoea. All the patients underwent surgery, 30 cases (68.2%)
      receiving total thymectomy and the rest a partial resection or biopsy. Marino
      Muller's histological classification showed the mixed type to be the most common
      (52.3%). Clinical staging was done according to the Masaoka classification, which
      gave the most common stage as stage III (34.1%). RESULTS: Twelve patients died
      during a mean follow-up of 8.2 +/- 3.5 years. The accumulated survival rate was
      77% at 5 years and 60% at 10 years. Analysis of the survival curves shows
      significant differences (P<0.05) when considering surgical technique, clinical
      staging and histological subtype. The multivariate analysis shows the only
      parameters with prognostic significance in PTENs to be clinical staging and
      histological type (P<0.001). CONCLUSIONS: The most important prognostic factors
      in PTENs are Masaoka's clinical staging and Marino-Muller's histological subtype.

PMID- 11825740
TI  - Long-term follow-up of video-assisted talc pleurodesis in malignant recurrent
      pleural effusions.
AB  - OBJECTIVE: Recurrent pleural effusion is a common condition and often presents a
      challenge for treatment. The aim of this report is to evaluate the long-term
      follow-up of thoracoscopic management of malignant recurrent pleural effusions.
      METHODS: From July 1st, 1992 to February 28th, 2001, out of 2311 VATS procedures
      performed at our Institution, 690 patients (29.85%) underwent videothoracoscopy
      (VATS) for recurrent pleural effusion. Of these 611 (88.55%) were treated for a
      malignant pleural effusion. There were 374 male and 237 female, with a mean age
      of 61.2 years. In all patients VATS was performed under general anaesthesia. The
      pleural effusion was carefully aspirated; fibrinous adhesions were taken down
      while dense fibrous adhesions were selectively divided; some limited
      decortications were also performed. Multiple pleural biopsies were always
      performed. Pleurodesis was performed with 5 g of sterile purified talc
      insufflated through a talc atomizer. One chest tube was left in situ for 3-5
      days. RESULTS: Operative mortality was 0.81% (five cases). Postoperative
      complications occurred in 19 cases (3.1%). Specific histologic diagnosis was
      obtained in all patients. Follow-up was available for 602 patients (98.5%). After
      a median follow-up of 64 months (range 5-105 months), talc pleurodesis was
      successful in controlling recurrence of effusion in 92.7% (558 out of 602) of
      patients. The success rate did not show any statistically significant difference
      between patients who underwent postoperative adjuvant therapy and patients who
      did not. In two patients with failure of talc pleurodesis a redo-VATS was
      performed. CONCLUSIONS: VATS represents the method of choice for both diagnosis
      and treatment of malignant recurrent pleural effusions. Talc poudrage is safe and
      effective in obtaining pleurodesis.

PMID- 11825742
TI  - Surgery for Mycobacterium avium complex lung disease in the clarithromycin era.
AB  - OBJECTIVE: Since the introduction of clarithromycin, it has been assumed that
      pulmonary Mycobacterium avium complex (MAC) disease can be treated with
      medication alone. This study examines whether surgery can still play an important
      role in the management of MAC lung disease in the current era. METHODS: Between
      April 1993 and January 2001, 21 patients (11 men and 10 women) underwent a
      pulmonary resection for MAC infection. The median age of the patients was 56
      years (range: 27-67 years). None of the patients were immunocompromised. Regimens
      employing clarithromycin were initiated preoperatively in all patients. The
      indications for surgery were failure of drug therapy in 19 patients and
      discontinuation of chemotherapy because of drug toxicity in two patients. The
      pulmonary resections (19 right lung, 2 left lung) performed included lobectomy in
      16 patients, pneumonectomy in three, bilobectomy in one, and lobectomy plus
      segmentectomy in one. RESULTS: All of the patients survived the surgery. Six
      major postoperative complications occurred in six patients (28.6%) and these
      included two bronchopleural fistulas after right pneumonectomy, two space
      problems, one prolonged air leak, and one case of interstitial pneumonia. All
      postoperative complications were manageable, and four of these were treated
      surgically. All patients had sputum-negative status after their operation.
      Relapse occurred in two patients (9.5%) at six months and two years
      postoperative, respectively. The first patient, who originally had a right upper
      lobectomy, underwent a left upper lobectomy during the follow-up period,
      attaining sputum conversion. The second patient underwent a right pneumonectomy
      and then died of respiratory failure four years postoperatively. This one late
      death was the only fatality. CONCLUSIONS: Although it is associated with
      relatively high morbidity, surgery provides a high sputum conversion rate for
      patients whose MAC disease responds poorly to drug therapy. Even in the present
      clarithromycin era, pulmonary resection remains the treatment of choice when MAC
      lung disease has not been successfully eradicated by drug treatment alone.

PMID- 11825743
TI  - Do women live longer following lung resection for carcinoma?
AB  - OBJECTIVE: To determine whether patient gender affects the outlook following lung
      resection for non-small cell lung cancer (NSCLC). PATIENTS AND METHODS:
      Prospectively collected data on 833 patients undergoing lung resection for NSCLC
      between 1990 and 2000 in a single unit were analysed. RESULTS: 581 patients were
      male (mean age 64.7 +/- 7 years) and 252 were female (mean age 62.6 +/- 7.8
      years) (P=0.006). Male patients were more likely to have a history of ischaemic
      heart disease (P=0.03), to have poorer preoperative spirometry as demonstrated by
      their % predicted FEV1 (P=0.02) and to need pneumonectomy (P=0.0001) than their
      female counterparts. Squamous cell carcinoma was the predominant histological
      cell type in men and adenocarcinoma in women (P<0.0001). There was a trend
      towards a lower pathological stage among women, but this was not significant.
      Operative mortality for men was 4.6 and 1.2% for women (P=0.01). Overall 5-year
      survival for men was 34.2 +/- 2.65% and 47.5 +/ - 4.2% for women (P=0.001) and,
      for the hospital survivors, was 36.5 +/- 2.7% and 48.1 +/- 4.2%, respectively
      (P=0.01). On univariate analysis, older age, the need for pneumonectomy and
      higher pathological stage were significant adverse factors whereas squamous cell
      type and female gender were significant favourable factors for survival (P<0.05).
      On Cox proportional hazards model (with and without hospital deaths),
      pathological stage (P<0.0001), female gender (P=0.0006) and squamous cell type
      (P=0.001) were independent predictors of survival. The survival was significantly
      better for women having squamous cell (P=0.01) or non-squamous cell cancers
      (adenocarcinoma and other) (P=0.002). Regarding the stage, women had a
      significant survival advantage at pathological stage I (P=0.01) and a relatively
      better survival at stage II and stage III disease (P=0.3). CONCLUSIONS: This
      study suggests that female gender exerts a significant positive effect on
      survival following lung resection for NSCLC. This effect is pronounced at early
      disease stage and persists after adjusting for important differences in the
      clinical, histo-pathological features and extent of pulmonary resection between
      male and female patients.

PMID- 11825744
TI  - Silicone T-tube for complex laryngotracheal problems.
AB  - OBJECTIVE: The use of a T-tube to manage complex laryngotracheal lesions, such as
      tracheal stenosis, tracheomalacia and tracheal injury, has previously been
      reported by other surgeons in the past. However, further validation of clinical
      details, including operative management and postoperative care, is needed.
      METHODS: From January 1991 to May 2000, 53 patients, including 24 with post
      tracheostomy stenosis, received 55 silicone T-tubes for transient or permanent
      stenting of the airway. There were 20 patients for subglottic stenosis; eight for
      long segment tracheostensis; seven with tracheal stenosis for severe
      cervicomediastinal fibrosis not amenable for reconstruction; six for complex
      tracheal injury; four for glottic injury; two each for tracheomalacia, failed
      tracheal surgery and tuberculotic tracheostenosis; and one each for tracheo
      esophageal fistula and necrotizing tracheitis. We retrospectively analyzed these
      patients. RESULTS: Thirty-eight out of 53 patients (71.8%) with T-tube stenting
      from 3 to 15 months was considered successful. Fifteen patients' operations
      failed due to patients' underlining diseases, previous intractable pulmonary
      infection, poor cognition and/or inadequate tube position. After removal of the
      tube, three patients (10.7%) developed partial airway obstruction with mild
      subglottic granulation tissue, which was resolved by carbon dioxide laser
      therapy. Two patients (7.1%) with prolonged tracheocutaneous fistula were
      conservatively treated by silver nitrate. CONCLUSION: Silicone T-tube can
      effectively resolve the complex laryngotracheal lesions with limited
      complications. Concurrent cardiopulmonary diseases and intractable infection were
      the two major causes for failure after the T-tube reconstruction.

PMID- 11825745
TI  - Enhanced expression of nitric oxide synthase in the early stage after increased
      pulmonary blood flow in rats.
AB  - OBJECTIVE: Evidence that vasodilator nitric oxide mediates normal pulmonary
      vascular tone has led to the hypothesis that endothelial injury induced by
      congenital heart disease with increased pulmonary blood flow disrupts these
      regulatory mechanisms and its associated altered vascular reactivity. Therefore,
      we hypothesized that increased pulmonary blood flow results in altered expression
      of endothelial nitric oxide synthase (eNOS). METHODS: We created an arteriovenous
      shunt in female Wistar (5-week-old) and measured the change of pulmonary blood
      flow and pressure immediately after and 1 month after the shunt operation. The
      protein levels of eNOS in the lung tissues of rats were assessed. RESULTS: The
      shunt immediately resulted in a significant increase in pulmonary blood flow
      (16.5 +/- 11.8% , pulmonary artery pressure (2.3 +/- 0.7 mm Hg), and blood O(2)
      saturation (16.1 +/- 11.8%) in the pulmonary artery. After 4 weeks, there was a
      significant increase in pulmonary blood flow (30.7 +/- 1.6%), pulmonary artery
      pressures (4.3 +/- 1.1 mm Hg), and blood O(2) content (43.3 +/- 17.5%). Western
      blot analysis demonstrated that eNOS protein was increased in the shunt lung 72 h
      after surgery and recovered to the control level 1 week later. CONCLUSION: This
      simple shunt model can induce early upregulation of eNOS expression with
      increased pulmonary blood flow and pulmonary artery pressure in rats.

PMID- 11825746
TI  - Pleural perforation of a saprophytic aspergilloma secondary to blunt chest
      trauma.

PMID- 11825747
TI  - Synovial cyst arising from pseudoarthrosis of a rib fracture following trauma.

PMID- 11825748
TI  - Giant neurofibroma of the chest wall.

PMID- 11825749
TI  - Giant cystic lymphangioma of the mediastinum.

PMID- 11825750
TI  - Type III dissection treated with percutaneous fenestration and stenting.

PMID- 11825751
TI  - Creating a bicuspid valve from the aortic wall: a new surgical approach on aortic
      valve disease (in vitro study).
AB  - We described a new technique (called 'bicuspidization'), which is performed by
      using autogenous material, without replacement of the aortic valves for the
      surgical treatment of aortic stenosis and/or insufficiency and tested it in in
      vitro sheep model. Different stress conditions were simulated by applying three
      different flow patterns (hemodynamic challenge tests) successively by using a
      centrifugal pump. It was demonstrated that the competency of the new bicuspid
      valves was excellent (zero insufficiency). There was a 10-11 mm Hg-increase on
      trans-valvular gradient comparing the normal hearts. The autogenous bicuspid
      valve has not blocked the way of the coronary flow in the closed position.

PMID- 11825752
TI  - The management of malignant pericardial effusions using permanently implanted
      devices.
AB  - We present a new approach utilising VATS and a Port-system (Medi-Port MP-GS9; IAP
      HMP) that allows home management of pericardial effusion in patients with
      advanced malignancy and recurrent effusion. All patients underwent thoracoscopic
      pericardial window under general anaesthesia. On completion of this procedure a
      Port-system was permanently implanted with the reservoir body placed in a
      subcutaneous pocket and the outlet catheter inserted into the pleural cavity
      which allows aspiration of the effusion at home, on becoming symptomatic.

PMID- 11825753
TI  - Radical video-assisted mediastinoscopic lymphadenectomy (VAMLA)--technique and
      first results.
AB  - Exact pretherapeutic lymph node staging of lung cancer is of special importance
      for selecting patients for neoadjuvant therapy or for video-assisted
      thoracoscopic resection. Staging is usually performed by computerized tomography
      scan and mediastinoscopy. However, these methods do not reach the accuracy of
      open nodal dissection. Therefore, we developed a technique of radical video
      assisted mediastinoscopic lymphadenectomy (VAMLA). In a prospective study, all
      VAMLA procedures were documented. Lymph nodes were counted and compared to open
      lymphadenectomy. In 40/46 patients, radical paratracheal and subcarinal
      dissection was achieved by VAMLA. An average number of 20.7 (5-60, SD 11.1) nodes
      was gained. This is comparable to our data from open lymphadenectomy.

PMID- 11825754
TI  - Cold abscess of the chest wall as an unusual complication of BCG vaccination.
AB  - Bacillus-Calmette-Guerin (BCG) vaccination often results in local adverse
      effects; however, serious or long-term complications are rare. The involvement of
      sternum among skeletal BCG osteomyelitis is a rarely seen complication of BCG
      vaccination. Such a complication may confuse with a chest wall tumor and a
      surgical intervention may be needed for the definite diagnosis. A 9-month-old
      infant who had a parasternal cold abscess in the anterior chest wall and sternal
      osteomyelitis of tuberculosis in the late period of BCG vaccination of whom the
      etiological diagnosis was histopathologically confirmed after surgery is
      presented and the preoperative diagnostic problems are discussed.

PMID- 11825755
TI  - Tracheal hamartoma: pericardial flap replacement of membranous tracheal wall.
AB  - We presented a rare case of large tracheal hamartoma in a 14-year-old boy and its
      management with a novel technique of reparation with pericardium of entire
      membranous portion of the trachea, after the failure of more conservative
      approaches like bronchoscopic resection and stenting. We remark the advantages of
      autologous material instead of prosthetic material.

PMID- 11825756
TI  - Fistulae of the internal thoracic vessels: report of two cases.
AB  - Arteriovenous fistulae involving the internal thoracic vessels are extremely
      rare. The multiple causes, variable clinical presentation, and inconsistent delay
      of onset of clinical symptoms in addition to their rarity make their diagnosis
      difficult. However, the complications of untreated internal thoracic fistulae are
      potentially fatal, emphasizing the need to make a prompt and correct diagnosis.
      Once the diagnosis is made and the investigational workup complete, treatment
      consists of either surgical ligation and excision or percutaneous transcatheter
      embolization. We report two cases of patients with internal thoracic fistulae:
      one arising as a complication of a tube thoracostomy and the other following an
      anterior thoracotomy. The second case report describes a rupture of the internal
      thoracic fistulae, a complication not reported earlier.

PMID- 11825757
TI  - The use of off pump surgery for management of penetrating coronary artery injury.
AB  - Penetrating trauma to the chest leading to coronary artery injury is associated
      with a high mortality rate, especially in the case of injury to the left anterior
      descending (LAD) coronary artery. The mortality rate remains high whether they
      are managed with primary ligation or with coronary artery bypass grafting using
      conventional cardiopulmonary bypass techniques. We report a case of proximal LAD
      coronary artery injury successfully treated with off pump coronary
      revascularisation.

PMID- 11825758
TI  - Bypassing a dilemma: intraoperative coronary angiography in acute aortic
      dissection.
AB  - Untreated coronary artery disease may complicate the clinical course of patients
      with Stanford type A acute aortic dissection. In these patients the role of
      coronary angiography for the assessment of coronary circulation is controversial
      and it is considered by some time consuming thus increasing the risk of rupture.
      We describe a case of acute type A aortic dissection that illustrates our
      approach to this problem.

PMID- 11825759
TI  - Complex and extensive infective endocarditis: a novel surgical approach.
AB  - Endocarditis involving the central fibrous body of the heart requires carefully
      planned surgical intervention. We present a novel approach in a 65-year-old male
      with extensive endocarditis involving the aortic root, ventricular septum,
      central fibrous body together with mitral, aortic and tricuspid valves.

PMID- 11825760
TI  - Fast track as a routine for open-heart surgery.

PMID- 11825762
TI  - A rarely seen cause of prosthetic mitral valve endocarditis: Salmonella
      enteritidis.

PMID- 11825763
TI  - Combined left pneumonectomy and off-pump coronary artery bypass: principles of
      cancer surgery.

PMID- 11825764
TI  - Sternal replacement using composite allograft.

PMID- 11825767
TI  - The risk of surgical procedures for the treatment of malignant respiratory
      fistulas.

PMID- 11825770
TI  - Chlamydia trachomatis genes whose products are related to energy metabolism are
      expressed differentially in active vs. persistent infection.
AB  - The Chlamydia trachomatis genome encodes glycolysis and pentose phosphate pathway
      enzymes, two ATP/ADP exchange proteins, and other energy transduction-related
      components. We asked if and when chlamydial genes specifying products related to
      energy transduction are expressed during active vs. persistent infection in in
      vitro models and in synovia from Chlamydia-associated arthritis patients. Hep-2
      cells infected with K serovar were harvested from 0-48 h post-infection (active
      infection). Human monocytes identically infected were harvested at 1, 2, 3, 5
      days post-infection (persistent). RNA from each preparation and from synovial
      samples PCR-positive/-negative for Chlamydia DNA was subjected to RT-PCR
      targeting (a) chlamydial primary rRNA transcripts and adt1 mRNA, (b) chlamydial
      mRNA encoding enzymes of the glycolysis (pyk, gap, pgk) and pentose phosphate
      (gnd, tal) pathways, the TCA cycle (mdhC, fumC), electron transport system (cydA,
      cydB), and sigma factors (rpoD, rpsD, rpoN). Primary rRNA transcripts and adt1
      mRNA were present in each infected preparation and patient sample; controls were
      negative for chlamydial RNA. In infected Hep-2 cells, all energy transduction
      related genes were expressed by approximately 11 h post-infection. In monocytes,
      pyk, gap, pgk, gnd, tal, cydA mRNA were present in 1-2-day-infected cells but
      absent at 3 days and after; cydB, mdhC, fumC were expressed through 5 days post
      infection. RT-PCR targeting mRNA from sigma factor genes indicated that lack of
      these gene products cannot explain selective transcriptional down-regulation
      during persistence. Analyses of RNA from synovial tissues mirrored those from the
      monocyte system. These data suggest that in the first phase of active chlamydial
      infection, ADP/ATP exchange provides energy required for metabolism; in active
      growth, glycolysis supplements host ATP. In persistence host, rather than
      bacterially produced, ATP is the primary energy source. Metabolic rate in
      persistent C. trachomatis is lower than in actively growing cells, as judged from
      assays for relative chlamydial primary rRNA transcript levels in persistent vs.
      actively growing cells.

PMID- 11825769
TI  - Roles of NKT cells in resistance against infection with Toxoplasma gondii and in
      expression of heat shock protein 65 in the host macrophages.
AB  - We investigated the roles of gamma delta T, NK, and NK1.1(+) T-like (NKT) cells
      in protective immunity against infection with Toxoplasma gondii. gamma delta T
      cells, NKT and NK cells, and NK cells in BALB/c mice were depleted by treatment
      with anti-TCR-gamma delta monoclonal antibody (mAb), anti-interleukin-2 receptor
      beta chain (IL-2R beta) mAb, and anti-asialoGM1 Ab, respectively, and these mice
      were infected with T. gondii. Treatment of mice with anti-TCR-gamma delta mAb
      aggravated toxoplasmosis, while treatment with anti-asialoGM1 Ab had no effects.
      Treatment with anti-IL-2R beta mAb enhanced the expression of heat shock protein
      65 (HSP65) and gamma interferon (IFN-gamma) mRNA, while it inhibited interleukin
      4 (IL-4) mRNA expression, ameliorating toxoplasmosis. In addition to NK cells,
      anti-IL-2R beta mAb eliminated cells expressing IL-2R beta and intermediate
      levels of CD3 (IL-2R beta(+) CD3(int)). Mice treated with anti-IL-2R beta mAb
      decreased the number of DX5(+) CD3(int) cells, which are considered to be
      equivalent to NK1.1(+)T cells in NK1.1 allele-negative strains. IL-2R beta(+)
      CD3(int) cells isolated from splenic and hepatic lymphoid cells were confirmed to
      express the TCR-V alpha 14 transcript. The magnitude of HSP65 induction in
      macrophages correlated with the protective potential against T. gondii infection
      after treatment with the antibodies, supporting our previous finding that gamma
      delta T cells play an essential role in the induction of HSP65 in host
      macrophages. Interestingly, NKT cells suppressed the expression of gamma delta T
      cell-induced HSP65 and IFN-gamma. Furthermore, depletion of IL-2R beta(+)
      CD3(int) cells suppressed the IL-4 mRNA expression. These results suggest that
      NKT cells may be the cells responsible for suppression of protective immunity
      against T. gondii infection by interfering with the gamma delta T cell-induced
      HSP65 expression, possibly through the generation of IL-4.

PMID- 11825771
TI  - Leishmania (L.) amazonensis-induced inhibition of nitric oxide synthesis in host
      macrophages.
AB  - Inhibition of lipopolysaccharide (LPS)-induced nitric oxide (NO) production was
      demonstrated in J774-G8 macrophages infected with Leishmania (L.) amazonensis
      promastigotes. The downmodulation of NO production observed in infected and LPS
      stimulated J774-G8 cells correlated with a reduction in inducible nitric oxide
      synthase (iNOS) activity. Reduction in iNOS activity was not paralleled by
      decreased iNOS mRNA expression, suggesting that the parasite affects post
      transcriptional events of NO synthesis. Supplementation with L-arginine or
      tetrahydrobiopterin did not increase NO production, suggesting that inhibition is
      not due to an insufficiency of substrate or co-factor. Treatment with anti-IL-10,
      anti-IL-4 or anti-TGF-beta neutralizing antibodies also failed to increase NO
      production, indicating that these cytokines are not involved in the observed
      parasite-induced inhibition of NO synthesis. However, treatment of the cultures
      with IFN-gamma resulted in a marked increase in NO production by infected LPS
      stimulated cells. These results show that although L.(L.) amazonensis infection
      inhibits iNOS activity and NO production by J774-G8 cells, activation by IFN
      gamma is capable of overriding the suppression of NO synthesis.

PMID- 11825772
TI  - Evaluation of anti-Plasmodium falciparum antibodies in Senegalese adults using
      different types of crude extracts from various strains of parasite.
AB  - To date, no consensus exists on the type of crude Plasmodium falciparum Ags to be
      used in a standard assay for the evaluation of the overall anti-blood-stage
      immune response in humans. Comparison of the dose-dependent reactivity of using a
      pool of hyper-immune Senegalese sera to saponin and water schizont extracts of
      the Senegalese 07/03 isolate indicated similar reactivity on both types of
      antigen preparations. Water schizont extracts from three different strains of P.
      falciparum adapted to in vitro culture probed with a panel of specific mouse
      antisera and monoclonal antibodies reacting with conserved antigens showed
      similar antigenic content. Seroreactivity of immune individuals living in three
      different areas of endemicity was assessed in parallel on water crude extracts.
      The individual IgG, IgM and IgG subclass antibody responses to the various
      schizont preparations correlated positively. The specific IgM response was higher
      on the Senegalese schizont extract than on the FCR3 extract and was highest in
      Dielmo villagers. The IgG response was similar in all three locations and was
      strain independent. These results indicate that monitoring IgG antibody levels to
      the widely distributed FCR3 strain using an easily prepared crude lysate might
      represent a valuable reference ELISA allowing homogenisation and comparison of
      data from different laboratories.

PMID- 11825773
TI  - The variant Arg110Gln of human IL-13 is associated with an immunologically hyper
      reactive form of onchocerciasis (sowda).
AB  - Onchocerca volvulus infection usually results in a predominantly immunopermissive
      reaction called generalized onchocerciasis and characterized by high
      microfilarial burden and immunological tolerance to the worms. Rarely, however,
      infection leads to the sowda form of the disease displaying low microfilarial
      numbers, i.e. microfilarial control, and a T helper 2 (Th2)-type immune response
      including high immunoglobulin (Ig)E levels, and interleukin (IL)-13 being one of
      the key cytokines. The aim of this study was to investigate a possible
      association of a variant of the IL-13 gene, which confers an IgE-independent risk
      for asthma and atopy, with the immunologically hyper-reactive sowda form of
      onchocerciasis. Genotyping for the IL-13 variant Arg110Gln revealed a highly
      significant association of Arg110Gln with the sowda form (relative risk of 2.98,
      n = 19 patients), whereas the frequency of the variant was significantly lower in
      patients with generalized onchocerciasis (n = 92 individuals). Sowda patients had
      higher IgE levels than those with generalized onchocerciasis. Logistic regression
      analysis revealed that IgE and IL-13 are independent variables, each increasing
      the relative risk for sowda. Arg110Gln has been suggested to lead to enhanced IL
      13 signaling and thus may be involved in shifting the immune reaction towards the
      hyper-reactivity characteristic for the sowda form, thereby promoting defense
      mechanisms.

PMID- 11825774
TI  - Monitoring of clinical and laboratory data in two cases of imported Lassa fever.
AB  - During 2000, four cases of fatal Lassa fever were imported from Africa to Europe.
      In two patients, consecutive serum samples were available for monitoring of virus
      load and cytokine levels in addition to standard laboratory data. Both patients
      had non-specific early clinical symptoms including high fever. Patient 1
      developed multi-organ failure and died of hemorrhagic shock on day 15 of illness,
      while patient 2 died of respiratory failure due to aspiration without hemorrhage
      on day 16. Ribavirin was administered to both patients beginning only on day 11.
      High serum aspartate aminotransferase and lactate dehydrogenase (LDH) levels were
      remarkable in both patients. Patient 1 had an initial virus load of 10(6) S RNA
      copies/ml as measured by real-time RT-PCR. Viremia increased steadily and reached
      a plateau of approximately 10(8)-10(9) copies/ml 4 days before death, while IFN
      gamma and TNF-alpha rose to extremely high levels only shortly before death. In
      contrast, in patient 2 the virus load decreased from 10(7) to 10(6) copies/ml
      during the late stage of illness which was paralleled by a decrease in the IFN
      gamma and TNF-alpha levels. The IL-10 level increased when specific IgM and IgG
      appeared. These data suggest that a high virus load and high levels of pro
      inflammatory cytokines in the late stage of Lassa fever play an important role in
      the pathogenesis of hemorrhage, multi-organ failure, and shock in Lassa fever.

PMID- 11825775
TI  - Regulation of naive and memory T-cell homeostasis.
AB  - Recent work has confirmed the existence of homeostatic mechanisms that regulate
      the overall size and composition of the mature T-cell pool. Homeostatic
      mechanisms not only control total T-cell numbers but appear to act differently on
      naive vs. memory cells. The roles of self-MHC/peptide ligands and certain
      cytokines in T-cell homeostasis are discussed.

PMID- 11825776
TI  - Immunity to hepatitis C virus: stunned but not defeated.
AB  - Hepatitis C virus (HCV) readily causes a persistent infection, although some
      individuals spontaneously control infection. 'Successful' immune responses appear
      to be multi-specific and sustained-including a major role for CD4(+)T cells. Some
      antiviral CD8(+)T cells show reduced capacity to secrete antiviral cytokines
      either temporarily ('stunning') or in the long term ('stunting'). The co
      ordination of multiple immune effector functions may be required to gain control
      of HCV.

PMID- 11825777
TI  - Slipping through the door: HIV entry into the nucleus.
AB  - HIV infection of non-dividing cellular targets like macrophages requires
      successful passage of the viral preintegration complex (PIC) across an intact
      nuclear envelope. Unique but redundant nuclear import signals reside within the
      HIV integrase, matrix, and Vpr proteins as well as the 'DNA flap'; these signals
      appear to facilitate PIC transport through the limiting nuclear pores. We discuss
      recent studies that have advanced our understanding of this key step in the HIV
      life cycle.

PMID- 11825778
TI  - Assembly of the type III secretion needle complex of Salmonella typhimurium.
AB  - The type III secretion needle complex (NC) of Salmonella typhimurium is a complex
      secretory system that functions to translocate virulence proteins into eukaryotic
      cells. Evolutionarily it is related to bacterial flagella. Assembly of the NC
      occurs through ordered secretion, polymerization, and assembly, and requires the
      coordinated expression and association of over 20 different proteins. Recent
      progress in the understanding of the assembly and architecture of the NC is
      reviewed.

PMID- 11825779
TI  - The endemic treponematoses.
AB  - Treponemal diseases comprise venereal syphilis (Treponema pallidum subsp.
      pallidum) and the endemic (non-venereal) treponematoses, i.e. yaws (T. pallidum
      subsp. pertenue), endemic syphilis (T. pallidum subsp. endemicum) and pinta (T.
      carateum). Treponemal diseases are distinguished on the basis of epidemiological
      characteristics and clinical manifestations. They are at present
      indistinguishable by morphological, immunological or serological methods. Several
      minor genetic differences have been identified among the subspecies. The endemic
      treponematoses have not yet been eliminated and are currently thought to affect
      at least 2.5 million persons. Renewed action towards the elimination of these
      diseases should be undertaken.

PMID- 11825780
TI  - Update on the epidemiology and transmission of Pneumocystis carinii.
AB  - Although Pneumocystis carinii pneumonia is one of the leading causes of morbidity
      and mortality among patients with the acquired immunodeficiency syndrome, many
      questions about its epidemiology and transmission remain unanswered. Whereas
      traditional theory postulates that the disease results from reactivation of
      latent infection, recent data suggest that active acquisition of infection,
      either through environmental exposure or person-to-person transmission, may
      occur. This review summarizes the current state of knowledge about the
      epidemiology and transmission of P. carinii and reports on evolving techniques
      that may improve our understanding of this organism in the future.

PMID- 11825781
TI  - Molecular insights into the history of plague.
AB  - Because of the limits inherent in historical sources on ancient plague epidemics,
      many questions concerning their etiology and epidemiology remain unanswered.
      Molecular biology tools and the use of dental pulp as a preserved source of
      bacterial DNA enabled us to demonstrate that Yersinia pestis was the etiologic
      agent of the 1347 European Black Death and of two additional epidemics in 1590
      and 1722 in southern France.

PMID- 11825782
TI  - Self and other through the prism of AIDS: a literary examination of relationships
      with patients.
AB  - This article examines how the "non-ill," often formal or informal caregivers,
      structure their relationships with "the ill," using as a specific example the
      disease of AIDS; and as a specific analytic tool selections of fictional writing.
      An introductory rationale explores why literature may be well-suited to helping
      us understand value-laden issues such as relationship. Discussion then focuses on
      how the professional and personal Self is identified and defined in relation to
      the suffering Other, through the development of concepts such as threat and
      boundary work. The concluding section suggests alternative relational models
      derived from more fluid and permeable definitions of Self and Other.

PMID- 11825783
TI  - Sub-Tenon's anesthesia.

PMID- 11825784
TI  - Laser polarimetry in the detection of glaucoma.

PMID- 11825788
TI  - Retinal detachment prophylaxis.

PMID- 11825790
TI  - Histoplasma capsulatum var. capsulatum.

PMID- 11825791
TI  - Giant cell arteritis.

PMID- 11825792
TI  - Macular hole surgery in high myopia.

PMID- 11825794
TI  - Giant cell arteritis.

PMID- 11825795
TI  - Giant cell arteritis.

PMID- 11825796
TI  - Giant cell arteritis.

PMID- 11825799
TI  - Are infantile hemangioma of placental origin?

PMID- 11825800
TI  - Primary transpupillary thermotherapy for small choroidal melanoma in 256
      consecutive cases: outcomes and limitations.
AB  - OBJECTIVE: The objective of this report was to evaluate ocular and systemic
      outcomes after primary transpupillary thermotherapy for choroidal melanoma and to
      identify the limitations of this treatment method. DESIGN: Noncomparative
      interventional case series. PARTICIPANTS: The participants included 256 patients
      with newly diagnosed choroidal melanoma. MAIN OUTCOME MEASURES: The outcome
      measures included local tumor recurrence and visual acuity. RESULTS: Before
      treatment, the mean tumor base was 7.1 mm, and mean tumor thickness was 2.7 mm.
      Overlying subretinal fluid was present in 215 cases (84%) and orange pigment on
      the tumor surface in 200 cases (78%). All tumors showed either photographic
      documentation of growth (114 cases; 45%) or substantial risk factors for growth
      (142 cases; 55%). After a mean of three treatment sessions, complete tumor
      control without recurrence was found in 232 cases (91%) and recurrence in 24
      cases (9%). The mean time to recurrence was 22 months, and the mean recurrent
      tumor size was 3.8 mm base and 2.4 mm thick. Of the recurrent tumors, additional
      thermotherapy was successful in controlling 13 (5%), plaque radiotherapy in 8
      (3%), and enucleation in 3 (1%). Using multivariable analysis, the risk factors
      for tumor recurrence included increasing number of thermotherapy sessions
      (reflecting less responsive tumor) (P = 0.0001) and optic disc overhung by tumor
      (P = 0.03). Kaplan Meier estimates revealed that 4% showed recurrence at 1 year,
      12% at 2 years, and 22% at 3 years follow-up. When analyzing those 214 patients
      without multivariable risk factors for recurrence, Kaplan Meier estimates for
      recurrence were 2% at 1 year, 8% at 2 years, and 10% at 3 years. The visual
      acuity after treatment was 20/20 to 20/40 in 128 cases (50%), 20/50 to 20/100 in
      47 (18%), and 20/200 or worse in 81 (32%). Using multivariable analysis, the most
      statistically significant factors at initial visit that were predictive of poor
      visual acuity (20/200 or worse) after treatment included documented tumor growth
      before treatment (P = 0.0001), mushroom tumor configuration (P = 0.002), initial
      symptom of blurred vision (P = 0.008), poor initial visual acuity (P = 0.005),
      superior quadrant tumor location (P = 0.03), underlying diabetes mellitus (P =
      0.04), and optic disc overhung by tumor (P = 0.04). Tumor-related mortality
      occurred in two patients (1%), one of whom showed complete tumor regression to
      thermotherapy and the other with diffuse choroidal melanoma and local tumor
      margin recurrence. CONCLUSIONS: Transpupillary thermotherapy is an effective
      treatment for certain small choroidal melanomas. Appropriate tumor selection is
      critical to successful treatment. Patients with tumors abutting or overhanging
      the optic disc or those requiring more than three sessions for tumor control are
      more likely to develop ultimate tumor recurrence. Transpupillary thermotherapy
      can cause damaging effects to the retina, leading to visual loss shortly after
      treatment.

PMID- 11825801
TI  - Biopsy in indeterminate intraocular tumors.
AB  - OBJECTIVE: To describe an intraocular biopsy technique that allows accurate
      histopathologic diagnosis in cases of clinically unclassifiable uveal tumors.
      DESIGN: Retrospective noncomparative consecutive interventional case series.
      PARTICIPANTS/METHODS: Intraocular biopsies were performed by a vitreous cutter
      either by a two-port clear cornea approach in 11 patients with unclassifiable
      iris tumors or by a three-port pars plana vitrectomy in 23 patients with
      unclassifiable choroidal tumors. Specimens were formalin fixed and paraffin
      processed. Hematoxylin-eosin and periodic acid-Schiff stains were performed in
      all cases, with additional immunohistochemical stains using the alkaline
      phosphatase, antialkaline phosphatase method in cases that could not be
      conventionally classified. MAIN OUTCOME MEASURES: Clinical observation and
      histopathologic examination of intraocular biopsies. RESULTS: In 97% of cases (n
      = 33) a definite diagnosis could be established by the biopsy specimen. A
      melanoma could be diagnosed in 73% of cases (n = 8) of iris tumors and in 57% of
      cases (n = 13) of posterior intraocular tumors. Other diagnoses included nevus,
      metastasis, vasoproliferative tumor, hemorrhage, gliosis, and scleritis.
      Complications were encountered in four cases: a vitreous hemorrhage occurred
      twice, an inconclusive biopsy result, and an intraocular tumor spread occurred
      once, respectively. No increased tumor-related mortality was observed after a
      mean follow-up of 44 months. CONCLUSIONS: Intraocular biopsy by a vitreous cutter
      allows the histopathologic examination of formalin-fixed paraffin-embedded tumor
      tissue. This increases the diagnostic accuracy, avoiding the risk of extraocular
      tumor spread seen with transscleral biopsy techniques.

PMID- 11825802
TI  - Orbital tumors in the older adult population.
AB  - PURPOSE: To determine the types and frequency of orbital tumors in the older
      adult population. DESIGN: Retrospective consecutive case series. PARTICIPANTS:
      Two hundred consecutive patients aged 60 years or older with an orbital tumor
      managed at a tertiary referral center. MAIN OUTCOME MEASURES: The relative
      incidence and management of orbital tumors in patients aged 60 years or older.
      RESULTS: Of approximately 950 consecutive patients with orbital space-occupying
      lesions managed over a 25-year period on the Oncology Service, 200 patients (21%)
      were 60 years or older at the time of diagnosis. The orbital tumor was unilateral
      in 183 patients (92%) and bilateral in 17 patients (8%). The most common clinical
      features at presentation included mass in 51 patients (26%), proptosis in 36
      (18%), and pain in 30 (15%). The mean duration of symptoms was 11 months before
      referral. The orbital tumor was malignant in 125 patients (63%) and benign in 75
      (27%). The most common diagnoses were malignant lymphoma in 47 patients (24%),
      idiopathic orbital inflammation in 19 (10%), and cavernous hemangioma in 15 (8%).
      The diagnosis was made with clinical findings and imaging studies in 58 patients
      (29%) and additional histopathologic examination in 142 patients (71%). Of 217
      tumors, the main tumor location was in the superior half of the orbit in 106
      lesions (49%), in the anterior orbit in 100 (46%), and in the extraconal space in
      135 (62%). Imaging studies showed a mass with well-defined margins in 90 tumors
      (41%) and ill-defined margins in 127 (59%). The tumors were solid in 203 cases
      (94%), cystic in 6 (3%), and mixed in 8 (3%). Over a mean of 31 months follow-up,
      50 (25%) patients had orbital tumor-related systemic involvement (metastasis or
      lymphoma), and 150 (75%) remained free of systemic involvement. CONCLUSIONS:
      Orbital tumors in the senior adult population are malignant in 63% of cases.
      Malignant lymphoma is the most common tumor in this age group, accounting for 24%
      of cases. Overall, 25% of patients have systemic problems related to the orbital
      process develop, so systemic evaluation is warranted.

PMID- 11825803
TI  - Successful treatment with 5-fluorouracil of conjunctival intraepithelial
      neoplasia refractive to mitomycin-C.
AB  - PURPOSE: To describe the histopathological findings and successful treatment with
      5-fluorouracil (5-FU) of a conjunctival intraepithelial neoplasia with limbal
      stem cell deficiency that was refractive to topical mitomycin-C (MMC). DESIGN:
      Interventional case report. INTERVENTION: A 64-year-old male patient presented
      with a diffuse conjunctival intraepithelial neoplasia (CIN) that was excised with
      concurrent keratoepithelioplasty. Because of a recurrence and the presence of
      limbal stem cell deficiency, he was placed on topical MMC. Despite two courses of
      MMC, the tumor size did not decrease, and topical 5-FU was started 1 year after
      MMC therapy began. Limbal autograft transplantation was performed thereafter.
      MAIN OUTCOME MEASURES: The clinical and histopathologic findings including
      impression cytology and biomicroscopic observations. RESULTS: After 5-FU
      treatment, the patient was free of the tumor clinically and cytologically, and
      the corneal surface had cleared. No recurrence was observed during the 30 months
      after the 5-FU therapy. Serious complications have not been observed.
      CONCLUSIONS: Topical 5-FU may be a therapeutic option for the treatment of
      patients with MMC-resistant CINs. The success of 5-FU is believed to be the
      result of a difference in the mechanism of cytotoxicity of MMC and 5-FU or the
      additive effects of the two agents.

PMID- 11825804
TI  - Anterior chamber infiltrates associated with systemic lymphoma: report of two
      cases and review of the literature.
AB  - PURPOSE: To describe the clinicopathologic features of two patients with systemic
      lymphoma who developed anterior chamber (AC) infiltrates of lymphoma cells.
      DESIGN: Two case reports and literature review. METHODS: The clinical and
      pathologic findings in two patients with AC infiltrates secondary to systemic B
      cell lymphoma are reviewed. MAIN OUTCOME MEASUREMENTS: Clinical observation and
      cytologic/flow cytometric examination of the infiltrate after AC aspiration.
      RESULTS: One patient presented with uveal infiltration, an exudative retinal
      detachment and an AC infiltrate. Systemic evaluation revealed a follicular
      lymphoma involving several groups of lymph nodes. The second patient with a known
      history of abdominal lymphoma was found to have blurred vision, photophobia and
      an AC infiltrate. Flow cytometric analysis of the AC infiltrate in both patients
      showed phenotypes consistent with the patients' systemic lymphomas. CONCLUSIONS:
      A pseudohypopyon in an adult may represent either the initial manifestation or a
      later complication of systemic lymphoma, similar to what has been reported in
      acute leukemia.

PMID- 11825805
TI  - Solitary spindle-cell xanthogranuloma of the eyelid.
AB  - PURPOSE: To describe a rare presentation of a solitary spindle-cell
      xanthogranuloma in a 3-year-old boy with a 6-month history of a right upper lid
      soft tissue lesion. DESIGN: Interventional case report. METHODS: An excisional
      full-thickness biopsy of the right upper lid was performed. Histologic
      examination and immunohistochemistry of the specimen were performed. RESULTS:
      Histopathologic evaluation revealed a well-demarcated nodule arising from the
      tarsus that contained a storiform array of spindle cells admixed with numerous
      multinucleated giant cells (some Touton type) and lymphocytes. The spindle cells
      labeled with antibodies to Factor XIIIa, CD68, lysozyme, Mac 387, and vimentin.
      The multinucleate giant cells labeled with CD68, lysozyme, and vimentin. Findings
      were consistent with the diagnosis of solitary spindle-cell xanthogranuloma.
      CONCLUSIONS: Spindle-cell xanthogranuloma resembles juvenile xanthogranuloma and
      fibrous histiocytoma (dermatofibroma) and should be considered in the
      differential diagnosis of spindle-cell tumors of the eyelid and periocular
      region. If similar lesions are noted elsewhere, the diagnosis of progressive
      nodular histiocytoma should be considered.

PMID- 11825806
TI  - Clinical characteristics of central serous chorioretinopathy in women.
AB  - PURPOSE: To describe the clinical features of central serous chorioretinopathy
      (CSC) in women and identify factors predictive of complete recovery, moderate
      visual loss, and prolonged duration. DESIGN: Retrospective observational case
      series. PARTICIPANTS: Eighty-four eyes in 78 women with CSC seen in our practices
      between 1982 and 1999. METHODS: Univariate and multivariate statistical analysis.
      MAIN OUTCOME MEASURES: Analyses of three outcome parameters: complete recovery
      (recovery of visual acuity and complete symptom resolution), moderate visual
      acuity loss (final acuity less than 20/40), and duration of symptoms greater than
      5 months. RESULTS: Sixty-two percent (52 of 84) achieved complete recovery over a
      median of 5 months (range, 2-108 months) and 88% (74 of 84) had a final vision of
      20/40 or better. Patients with subretinal precipitates (P = 0.001), single
      occurrence (P = 0.002), absence of hormone replacement therapy (HRT) (P = 0.01),
      duration less than 5 months (P = 0.02), or absence of a pigment epithelial
      detachment (PED) (P = 0.05) were more likely to recover completely. Recurrence (P
      = 0.03) and lack of subretinal precipitates (P = 0.03) were associated with a
      final vision less than 20/40. Age older than 50 (P = 0.004) and the presence of a
      PED (P = 0.02) were associated with duration longer than 5 months. CONCLUSIONS:
      In women, CSC associated with subretinal precipitates, shorter duration, single
      occurrence, lack of HRT use, and absence of PED is more likely to resolve
      completely. CSC occurring in women older than 50 or associated with PED formation
      is more likely to take longer to resolve.

PMID- 11825807
TI  - High-resolution stereoscopic digital fundus photography versus contact lens
      biomicroscopy for the detection of clinically significant macular edema.
AB  - PURPOSE: The purpose of this study was to compare high-resolution stereoscopic
      digital photography to contact lens biomicroscopy (CLBM) for the diagnosis of
      clinically significant macular edema. STUDY DESIGN: Comparative, prospective,
      observational case series. PARTICIPANTS: One hundred twenty diabetic patients.
      METHODS: Patients underwent clinical retinal examination with CLBM by a retinal
      specialist. On the same day as clinical grading, patients received high
      resolution stereoscopic digital imaging of the macula. The stereoscopic digital
      images were viewed using liquid crystal shutter goggles at least 2 months after
      clinical examination by a single masked grader for the presence or absence of
      diabetic retinopathy. MAIN OUTCOME MEASURES: Presence or absence of the Early
      Treatment of Diabetic Retinopathy Study criteria for clinically significant
      macular edema (CSME) overall, CSME 1, CSME 2, CSME 3, macular edema,
      microaneurysms, intraretinal hemorrhage, and hard exudate. RESULTS: Two hundred
      seven eyes of 105 patients had complete data sets from both diagnostic
      modalities. Exact agreement was high for all identified pathologic conditions:
      CSME overall, 83.6%; CSME 1, 83.6%; CSME 2, 96.1%; CSME 3, 88.5%; macular edema,
      75.0%; microaneurysms, 77.9%; intraretinal hemorrhage, 83.7%; and hard exudate,
      73.1%. Sensitivity ranged from 50.0% (CSME 2) to 90.6% (CSME overall).
      Specificity ranged from 90.0% (macular edema) to 99.0% (CSME 2). CONCLUSIONS:
      High-resolution stereoscopic digital photography is both sensitive and specific
      when identifying CSME and correlates well with the accepted standard of CLBM for
      the diagnosis of CSME.

PMID- 11825808
TI  - HLA-DR3 and DR4 and their relation to the incidence and progression of diabetic
      retinopathy.
AB  - PURPOSE: Cross-sectional data from the Wisconsin Epidemiologic Study of Diabetic
      Retinopathy indicated that patients with HLA-DR4, but not DR3, were more likely
      to have prevalent proliferative retinopathy than those without both antigens. We
      describe the relation of HLA-DR3 and DR4 antigens to the 14-year incidence and
      progression of diabetic retinopathy and macular edema in this cohort. DESIGN: A
      population-based cohort study. PARTICIPANTS: A probability sample of male and
      female patients receiving primary care for diabetes in 11 counties of southern
      Wisconsin. METHODS: Participants were invited for a baseline examination in 1980
      to 1982, with follow-up examinations at 4, 10, and 14 years later. At the 4-year
      examination, a random sample of participants (n = 428) diagnosed with diabetes
      before the age of 30 and taking insulin were selected for HLA-DR typing. MAIN
      OUTCOME MEASURES: Fourteen-year incidence and progression of diabetic retinopathy
      and macular edema based on masked stereoscopic fundus photographic grading.
      RESULTS: There was no relation between HLA-DR3 and DR4 status with the 14-year
      incidence and progression of diabetic retinopathy, progression to proliferative
      retinopathy, and incidence of macular edema. Patients with either HLA-DR3 or DR4
      were less likely to progress to proliferative retinopathy compared with those who
      were negative for both, although these relations were not statistically
      significant. The associations did not vary after adjusting for hypertension
      status, baseline retinopathy, and glycosylated hemoglobin levels, or after
      stratifying by duration of diabetes (less than 10 years vs. 10 years or more) and
      age at diagnosis of diabetes (less than 15 years vs. 15 years or more).
      Furthermore, 10-year mortality and 14-year nephropathy rates did not differ by
      HLA-DR3 or DR4 status, suggesting that selective mortality did not explain the
      pattern of associations seen. CONCLUSIONS: In contrast to the initial cross
      sectional findings, these data suggest that HLA-DR3 or DR4 status is unrelated to
      14-year incidence and progression of diabetic retinopathy. The discrepancy may be
      related to increasing homogeneity of retinopathy and diminishing power to detect
      small differences, but it may also reflect the uncertain and inconsistent effects
      of HLA-DR3 or DR4 on the development and progression of diabetic retinopathy.

PMID- 11825809
TI  - Cup-to-disc ratio, intraocular pressure, and primary open-angle glaucoma in
      retinal venous occlusion.
AB  - PURPOSE: To investigate the association of cup-to-disc ratio (CDR), intraocular
      pressure (IOP), and primary open-angle glaucoma (POAG) with the site of retinal
      venous occlusion (RVO) and optic nerve head swelling (ONHS). DESIGN: Prospective
      observational case series. PARTICIPANTS: Four hundred fifty consecutive cases
      from a single tertiary referral center. METHODS: Fundus photography of the
      retinopathy, 30 degrees stereo photography of the optic disc, and Goldmann
      applanation tonometry were the main parameters studied. The diagnosis of POAG was
      obtained from the referring ophthalmologist. MAIN OUTCOME MEASURES: The main
      outcome measures were the CDR, measured vertically through the center of the
      optic disc, and the site of RVO, identified as an arteriovenous (AV) crossing,
      optic cup, or optic nerve. Retinal venous occlusions occurring within the optic
      nerve were subdivided on the basis of the presence or absence of ONHS. RESULTS:
      There were poor correlations between CDR and IOP (r = 0.18; P = 0.000209) and CDR
      and age (r = 0.21; P = 0.000012). There were 197 AV crossing-sited RVOs (AV-RVOs)
      (43.8%) and 46 optic cup (OC)-sited RVOs (10.2%). The remainder occurred within
      the optic nerve; the ONHS group had 80 cases (17.8%) and the nonoptic nerve head
      swelling group (NONHS) had 127 cases (28.2%). The OC-RVO group tended to be the
      oldest of the four groups, whereas the ONHS group was the youngest (P <
      0.000001). The mean CDR was significantly higher in the OC-RVO (0.65) compared
      with the rest of the groups (0.45-0.48). The proportion of cases with CDR > or =
      0.7 was significantly higher in the OC-RVO group (39.1%) compared with the rest
      of the groups (0-6.3%). There was a trend (P = 0.000012) for IOP in the OC-RVO
      group (19.0 mmHg) and NONHS group (17.6 mmHg); the proportion of cases with IOP
      more than 21 mmHg was also higher in these cases (P = 0.00033). The prevalence of
      POAG was highest (P < 0.000001) in the OC-RVO group (39.1%) followed by the NONHS
      group (18.1%), ONHS group (8.8%), and AV-RVO (4.1%) group, respectively.
      CONCLUSIONS: Optic cup and optic nerve-sited RVO without ONHS are associated with
      raised IOP and may share a common management strategy aimed at controlling ocular
      pressure. Glaucomatous optic disc cupping, in contrast, seems to be important in
      the OC-sited RVO group only. Intraocular pressure, POAG, and glaucomatous optic
      disc cupping do not significantly seem to contribute to the development of RVO at
      an AV crossing or when the occlusion occurs within the optic nerve in association
      with ONHS.

PMID- 11825810
TI  - Homocysteine: a risk factor for retinal venous occlusive disease.
AB  - PURPOSE: Recent studies have shown a relationship between elevated levels of
      homocysteine and vascular disease including cerebrovascular accidents and
      myocardial infarctions. We evaluated patients with a recent retinal vein
      occlusion to determine if there was an associated elevation of homocysteine.
      DESIGN: Age and gender matched case-controlled study. PARTICIPANTS: Twenty
      patients with retinal venous occlusive disease within the previous 6-month period
      and 40 control patients without retinal venous occlusive disease were enrolled in
      the study. METHODS: Twenty patients with a history of retinal vein occlusion
      underwent laboratory testing to determine serum homocysteine levels. In addition,
      a health survey was completed and several laboratory tests relating to vascular
      disease including cholesterol were checked. Two control groups were selected. The
      first group included patients with diabetes and no history of retinal vascular
      occlusive disease. The second control group included nondiabetic patients who
      also had no prior history of retinal vascular occlusive disease. MAIN OUTCOME
      MEASURES: The main parameter measured in this study is fasting homocysteine.
      RESULTS: Fifteen of 20 patients (75%) with retinal vein occlusion disease had an
      elevated fasting serum homocysteine level, whereas only 5 of 40 control patients
      (13%) had an abnormal homocysteine level (P < 0.0005). CONCLUSIONS: Patients with
      retinal venous occlusive disease have higher levels of homocysteine, which may
      serve as a modifiable risk factor.

PMID- 11825811
TI  - Effect of noradrenaline on retinal blood flow in healthy subjects.
AB  - PURPOSE: To gain insight into the role of circulating catecholamines on retinal
      blood flow in vivo. DESIGN: Nonrandomized, open, crossover design. PARTICIPANTS:
      In 10 healthy male subjects, tyramine and noradrenaline were administered in
      stepwise increasing doses. These doses were selected to induce comparable changes
      in systemic blood pressure. METHODS: During each infusion step, retinal vessel
      diameter and retinal venous blood speed were measured with the Zeiss retinal
      vessel analyzer (Zeiss, Jena, Germany) and laser Doppler velocimetry,
      respectively. MAIN OUTCOME MEASURES: Retinal blood flow through a major temporal
      vein was calculated. RESULTS: As expected, tyramine and noradrenaline induced a
      systemic hypertensive response. Tyramine caused a moderate increase in
      noradrenaline plasma levels, whereas exogenous noradrenaline increased
      noradrenaline plasma levels more than 10-fold. Nevertheless, neither tyramine nor
      noradrenaline induced any effect on retinal hemodynamic parameters. CONCLUSIONS:
      These data indicate that even high levels of circulating noradrenaline have
      little impact on retinal vascular tone and retinal blood flow. Hence, the
      adrenergic system appears not to play a major role in retinal blood flow
      regulation.

PMID- 11825812
TI  - Photodynamic therapy with verteporfin in mallatia leventinese.
AB  - OBJECTIVE: To describe a case of a patient with documented genetic mallatia
      leventinese who developed a classic choroidal neovascular membrane and underwent
      photodynamic therapy (PDT) with verteporfin (Visudyne; CIBA Vision Corp., Duluth,
      GA). DESIGN: Interventional case report. INTERVENTION: The patient underwent a
      complete ophthalmologic evaluation and fluorescein angiography. Photodynamic
      therapy with verteporfin was performed. MAIN OUTCOME MEASURES: Clinical and
      angiographic records were analyzed for evidence of changes in visual acuity,
      clinically evident subretinal fluid and the extent of fluorescein leakage from
      choroidal neovascularization (CNV). RESULTS: Three weeks after treatment, a
      fluorescein angiogram showed closure of the neovascular membrane, no evident
      subretinal fluid was seen, and visual acuity had improved from 20/60- to 20/40.
      Nine weeks after the application, fluorescein angiography demonstrated a
      microscopic hyperfluorescent spot at the site of the previously active CNV at
      which a small area of shallow subretinal fluid was observed, and visual acuity
      was 20/50. Thirty-four weeks after PDT, visual acuity was 20/60, subretinal fluid
      resolved, and fluorescein angiography did not show any further changes.
      CONCLUSIONS: Photodynamic therapy with verteporfin may be considered as a
      possible treatment in patients with mallatia leventinese who develop classic CNV.

PMID- 11825813
TI  - Randomized controlled clinical trial of beta irradiation as an adjunct to
      trabeculectomy in open-angle glaucoma.
AB  - OBJECTIVE: To assess the effect of a single intraoperative application of 750 cGy
      of beta irradiation on the outcome of trabeculectomy for uncontrolled open-angle
      glaucoma. DESIGN: A prospective, randomized, double-blind, placebo-controlled
      clinical trial. PARTICIPANTS: Sixty-one eyes of 61 Caucasian patients at low risk
      of filtering surgery failure, with poorly controlled primary or secondary open
      angle glaucoma undergoing routine trabeculectomy. METHOD: Patients were randomly
      assigned to control or beta irradiation groups. All patients underwent standard
      trabeculectomy with fornix-based conjunctival incision. Eyes assigned to beta
      irradiation received 750 cGy of beta irradiation directly over the sclerostomy
      site on completion of conjunctival suturing. An identical but inactive applicator
      was applied to control eyes, delivering no radiation. Both operator and patient
      remained masked to the assignment for the 12-month follow-up period. MAIN OUTCOME
      MEASURES: The main outcome measure was intraocular pressure (IOP) control.
      Complete success of IOP control was defined as an IOP less than 21 mmHg at 12
      months without need for additional medication. Qualified success was defined as
      an IOP less than 21 mmHg at 12 months where additional medication was required.
      RESULTS: Complete success of IOP control was achieved in 19 (86%) control eyes
      and 35 (90%) irradiated eyes (P = 1.0). Qualified success of IOP control was
      achieved in 21 (95%) control eyes and 39 (100%) irradiated eyes at 12 months
      follow-up (P = 1.0) CONCLUSIONS: We experienced a very high success rate of
      filtration surgery in this select population without adjunctive irradiation. Our
      sample size was too small to show any improvement in success with use of beta
      irradiation in this group. Other studies would have to be done to determine
      whether it may have measurable benefit in cases with a high risk of filtration
      failure.

PMID- 11825814
TI  - Three-month comparison of brimonidine and latanoprost as adjunctive therapy in
      glaucoma and ocular hypertension patients uncontrolled on beta-blockers:
      tolerance and peak intraocular pressure lowering.
AB  - PURPOSE: To compare the tolerance and peak intraocular pressure (IOP)-lowering
      efficacy of brimonidine and latanoprost as adjunctive therapy in patients with
      ocular hypertension or glaucoma uncontrolled on beta-blockers. DESIGN: A
      prospective, multicenter, double-masked, parallel-design clinical trial.
      PARTICIPANTS: One hundred fifteen patients with IOP inadequately controlled on
      topical beta-blocker monotherapy. METHODS: Patients were randomly assigned to
      receive brimonidine, 0.2%, twice a day or latanoprost, 0.005%, every day as
      adjunctive therapy for 3 months. After 1 month of adjunctive treatment, patients
      who failed to meet a target 15% reduction in IOP at peak drug effect were crossed
      over to the other study medication. The target sample size of 51/group gave a
      power of 0.80 to detect a difference of 1 mmHg in mean IOP lowering between
      groups. MAIN OUTCOME MEASURES: The primary outcome variables were reduction in
      IOP from baseline at peak drug effect, response rate, and quality of life as
      measured using the Glaucoma Disability Index. RESULTS: Mean beta-blocker-treated
      baseline IOP was comparable between treatment groups (approximately 21.3 mm Hg).
      After 1 month of adjunctive therapy, brimonidine and latanoprost provided
      comparable IOP lowering (4.88 mmHg [22.8%] with brimonidine and 5.01 mmHg [23.5%]
      with latanoprost, P = 0.798). Response rates were similar in both groups, with 44
      of 54 brimonidine patients and 43 of 53 latanoprost patients achieving the
      minimum target 15% IOP reduction at peak drug effect at month 1 (P = 0.963).
      Among patients who were successful at month 1 and continued on the initial study
      medication, mean IOP reductions were 4.55 mmHg with brimonidine and 5.49 mmHg
      with latanoprost (P = 0.149) at month 3. There was no significant difference in
      the ability of brimonidine and latanoprost to maintain at least a 15% additional
      reduction in IOP for 3 months (28 of 38 patients on brimonidine vs. 30 of 36
      patients on latanoprost achieved > or =15% IOP reduction at month 3; P = 0.314).
      Patients in the latanoprost group were more likely to report negative quality-of
      life variables than patients in the brimonidine group. Significantly more
      latanoprost patients reported watery or teary eyes (34 of 53, 64.2% vs. 23 of 54,
      42.6% with brimonidine; P = 0.025) and hands and feet that became cold easily (24
      of 53, 45.3% vs. 12 of 54, 22.2% with brimonidine; P = 0.012). CONCLUSIONS: As
      adjunct therapy with beta-blockers, brimonidine twice daily and latanoprost every
      day were comparable in lowering IOP at peak effect, but brimonidine was better
      tolerated, with fewer reports of adverse quality-of-life effects.

PMID- 11825816
TI  - Diode laser cyclophotocoagulation: role in the management of refractory pediatric
      glaucomas.
AB  - PURPOSE: To report the efficacy and complications of diode laser
      cyclophotocoagulation (cyclodiode) in the management of refractory pediatric
      glaucomas. DESIGN: Noncomparative interventional case series. PARTICIPANTS:
      Pediatric patients with uncontrolled glaucoma. Seventy-seven eyes of 61 patients
      underwent cyclodiode. Mean age was 7.4 years (range, 0.4-17 years). MAIN OUTCOME
      MEASURES: Intraocular pressure (IOP), visual acuity, complications. RESULTS:
      Diagnoses included aphakic glaucoma, congenital glaucoma, juvenile chronic
      arthritis, aniridia, anterior segment dysgenesis, and Sturge-Weber syndrome.
      Sixty percent of eyes were aphakic, and 64% had undergone at least one previous
      surgical procedure for glaucoma. Patients underwent a mean of 2.3 treatment
      sessions per eye (maximum, 8 sessions). Mean pretreatment IOP was 32.0 mmHg.
      After one treatment session, 62% had a clinically useful reduction in IOP (<22
      mmHg or by 30%), but this had fallen to 37% by 12 months. With repeat cyclodiode,
      72% had a clinically useful reduction in IOP for a year or more (mean, 8.4-month
      interval between treatments). Aphakic eyes had a more sustained IOP reduction (P
      < 0.01 log rank test). Of treatment failures, 13% had no useful IOP response, and
      three eyes developed subsequent retinal detachment and loss of vision. No other
      eyes lost vision because of cyclodiode-related complications. In 5.5% of the
      treatment sessions there was a significant posttreatment inflammatory episode.
      Cyclodiode treatment did not enable a reduction in the number of medications.
      CONCLUSIONS: With repeated treatment, cyclodiode can provide effective control of
      IOP. However, the success rate is lower than with adults, and younger eyes may
      recover from treatment more rapidly. Although response may be temporary,
      cyclodiode has a lower rate of severe adverse effects than surgical modalities
      and has roles as a temporizing measure, as an adjunct to surgery, or in managing
      selected patients in whom surgery is undesirable because of a high risk of
      surgical complications.

PMID- 11825817
TI  - When may the posterior capsule be preserved in pediatric intraocular lens
      surgery?
AB  - PURPOSE: To refine indications for primary posterior capsulotomy (PPC) in
      conjunction with posterior chamber intraocular lens (PCIOL) implantation for
      cataract in childhood. DESIGN: Noncomparative case series. PARTICIPANTS: Patients
      1 to 13 years old who underwent cataract extraction with intent to preserve the
      posterior lens capsule and PCIOL implantation between January 1992 and December
      1998 at a pediatric hospital. METHODS: Medical records were reviewed to determine
      the frequency and timing of posterior capsule opacification (PCO) after PCIOL
      surgery with preservation of an intact posterior capsule. Comparison of
      pseudophakic PCO rates for groups defined by age and several possible risk
      factors. Assessment of safety and efficacy for PPC with anterior vitrectomy
      performed through a limbal incision in cases where the posterior capsule could
      not be preserved. MAIN OUTCOME MEASURES: Need for neodymium:yttrium-aluminum
      garnet laser capsulotomy or surgical membranectomy to treat PCO. RESULTS: PCO
      occurred in 40% of 30 eyes with intact posterior capsule. Mean follow-up duration
      was 22 months for eyes that had PCO develop and 24 months for those in which the
      posterior capsule remained clear. Laser capsulotomy was required for 64% of 14
      eyes in the 1- to 6-year-old age range but for only 19% of 16 in the 6- to 13
      year-old range (P < 0.05). Mean time from surgery to PCO was 7 months for the
      younger group and 13 months for the older group. A need for repeated capsulotomy
      (one eye) or membranectomy with anterior vitrectomy (two eyes) was found only in
      the younger age group. There was no association of PCO with trauma history,
      cataract type, residual lens cortex, IOL position, or postoperative fibrin clot.
      Final vision was possibly compromised as a result of PCO in one eye with
      amblyopia. None of 24 eyes in which PPC with anterior vitrectomy was performed
      out of intraoperative necessity before primary PCIOL implantation had secondary
      opacification develop. No reduction in postoperative vision was attributable to
      PPC. CONCLUSIONS: PPC seems to be advisable for children less than 6 years old
      when cataract extraction with PCIOL implantation is performed. Preservation of
      the posterior capsule remains appropriate for older children with pseudophakia.

PMID- 11825819
TI  - Preservation of anterior capsule during vitrectomy and lensectomy for retinal
      detachment with proliferative vitreoretinopathy.
AB  - PURPOSE: To report a series of 15 eyes with rhegmatogenous retinal detachment and
      proliferative vitreoretinopathy (PVR) or at high risk for advanced PVR, which
      underwent pars plana vitrectomy (PPV) and lensectomy (PPL) with preservation of
      the anterior capsule. DESIGN: Retrospective noncomparative case series.
      PARTICIPANTS: Fifteen consecutive patients with retinal detachment and varying
      degrees of PVR in one eye. METHODS: All eyes had undergone PPV and PPL with
      preservation and polishing of the anterior capsule and had at least 6 months of
      follow-up. Of the 15 eyes, grade C PVR was present preoperatively in 11 and was
      anterior in 5. Seven of 15 eyes had gas and 8 of 15 had silicone oil tamponade.
      Eight of 15 eyes had subsequent posterior chamber intraocular lens (PCIOL)
      placement; 5 eyes had simultaneous silicone oil removal. One eye had a PCIOL
      placed at the time of the PPL. MAIN OUTCOME MEASURES: Visual acuity, retinal
      reattachment, complications of gas or silicone oil tamponade, and anterior
      capsular clarity. RESULTS: Fourteen eyes had complete retinal reattachment at the
      final visit (1 of 15 had macular redetachment only). Final visual acuity was
      better or equal to preoperative acuity in all eyes, improving by 4 +/- 4 lines
      overall. No eyes had corneal decompensation, pupillary block, or other vision
      threatening anterior segment complication. The anterior capsule remained
      centrally clear in the 13 eyes that did not have a primary central capsulotomy.
      One eye with minimal preoperative PVR developed hypotony. CONCLUSIONS:
      Vitreoretinal surgeons can preserve the anterior capsule in eyes with retinal
      detachment and PVR to help prevent intraoperative and postoperative complications
      of gas or silicone oil, simplify future PCIOL placement, and maintain a normal
      iris appearance.

PMID- 11825820
TI  - Microscope-induced retinal phototoxicity in cataract surgery of short duration.
AB  - OBJECTIVE: Microscope-induced retinal phototoxicity has been described after
      prolonged cataract surgery, usually in operations lasting longer than 100
      minutes. The purpose of this study was to compare the features of microscope
      induced retinal phototoxicity occurring in patients who underwent cataract
      surgery of short duration and long duration. DESIGN: A retrospective
      nonrandomized comparative trial. PARTICIPANTS: Thirty-four patients, whose
      medical records documented the development of phototoxic lesions in the retina as
      a result of cataract surgery, were divided into two groups: group A with 14
      patients whose operating time was 30 minutes or less, and group B with 20
      patients whose operating time was greater than 30 minutes. INTERVENTION: All
      patients underwent either phacoemulsification or extracapsular cataract
      extraction (ECCE) with implantation of an intraocular lens. RESULTS: The mean
      operating time was 23.1 minutes (range, 11-30 minutes) in group A, and 60.8
      minutes (range, 34-123 minutes) in group B. Phacoemulsification was done more
      often in group A (P = 0.001) and ECCE in group B (P = 0.0003). A final refraction
      of +/- 1 D was achieved by 12 eyes (86%) in group A and by 12 eyes (60%) in group
      B (P = 0.11). The correlation between final refraction and duration of the
      operation was significant; the closer the final refraction approached to
      emmetropia, the shorter the duration of surgery (r = 0.53; P = 0.001). Diabetic
      retinopathy was more common in group A (P = 0.03). CONCLUSIONS: Phototoxic
      lesions of the retina may occur during cataract surgery even when the duration of
      the operation is short. The most relevant associated factors found in this study
      were correction approximating emmetropia and diabetic retinopathy.

PMID- 11825821
TI  - Progression of keratoconus assessed by fourier analysis of videokeratography
      data.
AB  - OBJECTIVE: To quantitatively document changes in corneal refractive parameters in
      relation to the progression of keratoconus over years. DESIGN: Retrospective
      observational case series. PARTICIPANTS: Eighty-five eyes of 64 patients with
      keratoconus who had undergone videokeratography examinations at least twice with
      an interval of 1 year or longer between each examination. METHODS: By means of
      Fourier series harmonic analysis, topography data were decomposed into spherical
      component, regular astigmatism, decentration component, and higher order
      irregularity. MAIN OUTCOME MEASURES: Change rate of each parameter per year was
      calculated by use of the least squares method. RESULTS: All four refractive
      parameters were significantly larger in the keratoconic eyes than in the age
      matched normal controls (P < 0.001, Student's t test). The yearly rate of change
      was significantly positive for spherical component (P = 0.008) and higher order
      irregular astigmatism (P = 0.015) but not for the regular astigmatism and
      decentration component. In eyes that showed apparent progression on color-coded
      maps, spherical component showed a significantly positive change rate per year (P
      = 0.002), but other parameters did not. In eyes without apparent progression, the
      yearly change rate of higher order irregular astigmatism was significantly larger
      than zero (P = 0.049). CONCLUSIONS: Keratoconus progression over years was
      quantitatively described. It was indicated that spherical equivalent is a
      manifest indicator for the apparent progression of keratoconus, and irregular
      astigmatism increases along with the natural course of the disease.

PMID- 11825822
TI  - Possible role of the vitamin E solubilizer in topical diclofenac on matrix
      metalloproteinase expression in corneal melting: an analysis of postoperative
      keratolysis.
AB  - OBJECTIVE: To analyze tissue matrix metalloproteinase (MMP) expression in three
      patients who developed postoperative corneal melts after treatment with topical
      diclofenac sodium 0.1% (Falcon; Fort Worth, TX) ophthalmic solution. DESIGN:
      Retrospective noncomparative interventional case series with tissue analysis.
      MAIN OUTCOME MEASURES: Three patients were examined in this study. We report two
      patients from the same center with acute corneal melts after uncomplicated
      photorefractive keratectomy (PRK). Prior to these cases, 1500 patients were
      treated at the Zale Lipshy University Laser Center for Vision with no adverse
      effects. All 1500 patients were treated with the same postoperative regimen of
      ciprofloxacin, rimexolone, and suprofen ([Profenal, (CIBA, Duluth, GA]). The next
      27 cases were treated postoperatively with ciprofloxacin and rimexolone. However,
      diclofenac sodium 0.1% was used instead of Profenal. A third case was also
      discussed. This melt occurred at another center in a postoperative cataract
      patient who developed cystoid macular edema after cataract extraction with
      intraocular lens placement. He was initially treated with diclofenac sodium 0.1%
      (Ciba Vision, Duluth, GA) then with diclofenac sodium 0.1%. He subsequently
      developed a corneal perforation requiring penetrating keratoplasty. All tissue
      specimens were examined by light microscopy. Microbiologic cultures and stains
      were also performed. Immunolocalization and in situ hybridization were performed
      on all keratoplasty specimens to detect expression and localization of MMPs. All
      patients had a complete diagnostic evaluation for systemic autoimmune diseases.
      RESULTS: Postoperatively, all patients developed corneal perforations requiring
      surgical intervention while being treated with diclofenac sodium 0.1%.
      Microbiologic cultures and special stains were negative for microorganisms.
      Induced expression of specific tissue degrading enzymes of the matrix
      metalloproteinase family was demonstrated within corneal epithelial cells,
      stromal keratocytes, and at the level of Descemet's membrane. The uniform
      distribution pattern of expression was not consistent with the localization
      expected of a repair response, suggesting the involvement of some outside agent.
      CONCLUSIONS: Whereas MMP expression is a normal component of repair, excessive or
      inappropriate MMP activity is associated with corneal keratolysis. Our study
      provides preliminary evidence that topical application of diclofenac sodium 0.1%
      may be associated with aberrant MMP expression in the cornea.

PMID- 11825823
TI  - Amniotic membrane in the surgical management of acute toxic epidermal necrolysis.
AB  - OBJECTIVE: To report a new surgical technique to manage severe acute toxic
      epidermal necrolysis. DESIGN: Two interventional case reports. PARTICIPANTS: Two
      patients. Case 1: A 6-year-old boy had severe toxic epidermal necrolysis develop
      after being treated with trimethoprim and sulfamethoxazole for chronic otitis
      media. Both eyes and eyelids were affected. He underwent bilateral lysis of
      symblepharon and all adhesions and bilateral amniotic membrane transplantation to
      the entire ocular surface except the cornea. Loss of eyelid skin required
      transplantation of amniotic membrane to all four eyelids and strips of amniotic
      membrane at the eyelid margins. Case 2: An 8-year-old girl with severe toxic
      epidermal necrolysis associated with mycoplasma pneumonia had bilateral, diffuse
      keratoconjunctivitis, diffuse corneal epithelial defects, and bilateral
      symblepharon. Amniotic membrane transplantation was performed bilaterally, using
      a symblepharon ring in the left eye. INTERVENTION: Amniotic membrane
      transplantation. MAIN OUTCOME MEASURES: Preservation of normal ocular and eyelid
      surfaces and prevention of blindness. RESULTS: Case 1: Thirty-six months after
      bilateral ocular surgery, there is no symblepharon, good ocular surface wetting,
      and an uncorrected bilateral vision of 20/20. Case 2: Amniotic membrane
      transplantation protected both ocular surfaces and prevented conjunctival
      contracture without adhesion of the eyelids to the ocular surface. The central
      vision was preserved. There was minimal peripheral corneal vascularization and
      mild conjunctival scarring of the tarsal conjunctival surface 34 months
      postoperatively. CONCLUSIONS: These are the first cases of acute toxic epidermal
      necrolysis treated with amniotic membrane transplantation and the first use of
      the procedure on external eyelid surfaces with good healing of the eyelids. This
      new treatment for acute toxic epidermal necrolysis preserves normal ocular and
      eyelid surfaces and may prevent blindness.

PMID- 11825824
TI  - The Universal Standard Scale: proposed improvements to the American National
      Standards Institute (ANSI) scale for corneal topography.
AB  - PURPOSE: To evaluate the American National Standards Institute (ANSI) corneal
      topography scale (ANSI Z-80.23-1999) and to develop a Universal Standard Scale
      (USS) based on scientific principles and clinical usefulness. DESIGN:
      Retrospective data analysis and computer modeling of frequency of corneal power
      distributions. METHODS: Four variations of corneal topography color scales were
      constructed using the ANSI standard description. The scales used 21 contour
      intervals with step sizes of 0.5, 1.0, or 1.5 diopters (D). In example 1, hue was
      varied, whereas saturation and brightness were held constant. In example 2, hue
      was varied systematically, whereas luminance was varied to compensate for
      spectral sensitivity. In example 3, hue was varied, whereas luminance was
      adjusted to improve color contrast at the center of the scale. In example 4, the
      palette was generated by varying the red, green, and blue color intensity levels.
      In the USS, colors were defined by hue, brightness, and saturation, and
      appearance was optimized by using contrast. The contour interval was determined
      from the standard deviation of keratometry for 27 normal corneas. The scale range
      was based on corneal powers found in 388 topography maps of 12 different corneal
      conditions. RESULTS: ANSI-derived maps were difficult to interpret because of
      poor color contrast and the inability to associate contours with specific colors
      in the scale. The 0.5 D interval slightly improved the appearance of some
      patterns but reduced the useful clinical range of the scale. ANSI colors did not
      match the user's expectations; abnormal patterns appeared in shades of green,
      which is associated with normality. The standard deviation of keratometry
      readings for the normal population was 1.59 D. Hence, the contour interval for
      the USS was set to 1.5 D. More than 99.9% of the corneal powers in 388 clinical
      maps were within the range of 30 to 67.5 D, which was chosen as the range for the
      USS. CONCLUSIONS: The ANSI scale for corneal topography is a series of scales
      that lead to clinical misinterpretations. The alternative USS would provide
      uniform presentation, unambiguous interpretation, and greater ease of comparison
      among maps produced by different topographers.

PMID- 11825825
TI  - Long-term follow-up of patients treated with short-term high-dose chlorambucil
      for sight-threatening ocular inflammation.
AB  - PURPOSE: To determine the effectiveness of short-term high-dose chlorambucil in
      the treatment of sight-threatening uveitis and to ascertain the incidence of
      severe side effects, particularly late malignancy. DESIGN: Retrospective,
      noncomparative interventional case series. PARTICIPANTS: Fifty-three patients
      treated at the University of Illinois at Chicago Eye and Ear Infirmary and the
      private office of one of the authors for severe sight-threatening uveitis.
      METHODS: Treatment with short-term high-dose chlorambucil (2-9 months of
      therapy). MAIN OUTCOME MEASURE: Visual acuity and degree of inflammation were
      assessed at every visit. The development of systemic side effects, including
      malignancy, was assessed using a detailed questionnaire. RESULTS: Total
      cumulative dose of chlorambucil ranged from 392 to 5200 mg with an average of
      1429 mg. The maximum daily dose ranged from 10 to 30 mg with an average of 20 mg.
      Average duration of treatment was 16 weeks with a range of 7 to 40 weeks. Seventy
      seven percent of patients treated were in remission with an average follow-up of
      4 years (range: 6 months to 24 years). Forty-seven percent had at least two lines
      of improvement in Snellen visual acuity after treatment, with an average gain of
      3.5 lines. Adverse effects include secondary amenorrhea, nonophthalmic herpes
      zoster, testicular atrophy, and erectile dysfunction. None of the patients had
      developed a malignancy as of their last follow-up. CONCLUSION: Short-term high
      dose chlorambucil therapy may be a reasonable option in patients with intractable
      sight-threatening uveitis.

PMID- 11825826
TI  - Multifocal choroiditis and panuveitis: immunomodulatory therapy.
AB  - PURPOSE: To report our analysis of the efficacy of immunomodulatory therapy on
      the course of 19 patients with multifocal choroiditis and panuveitis (MCP).
      DESIGN: Retrospective, noncomparative, interventional case series. PARTICIPANTS:
      Nineteen patients with multifocal choroiditis with panuveitis evaluated on the
      Ocular Immunology and Uveitis Service of the Massachusetts Eye and Ear Infirmary
      from 1978 to 2000. METHODS: Fifteen patients were treated with systemic
      immunomodulatory therapy; 4 patients (who refused therapy) were treated with
      systemic steroids. All patients were analyzed for control of inflammation, visual
      acuity outcome, and tolerance of immunomodulatory therapy. MAIN OUTCOME MEASURES:
      Control of inflammation and visual acuity. RESULTS: Nineteen patients with
      bilateral MCP with a mean follow-up of 72.7 months were studied. Fifteen were
      treated with immunomodulatory agents, whereas 4 patients received only systemic
      steroids; these 4 developed serious systemic steroid-related complications, and
      12 others had cataract and/or glaucoma related to chronic topical, regional, or
      systemic steroid use before immunomodulatory therapy. Two patients who refused
      immunomodulatory therapy lost considerable vision in three of their four eyes. Of
      the 15 patients treated with immunomodulatory drugs, 7 patients lost considerable
      vision in one eye on steroid therapy but maintained good vision in the other eye
      once immunomodulatory therapy was instituted. No patient lost vision in any eye
      once he or she was treated with immunomodulatory treatment. CONCLUSIONS:
      Immunomodulatory therapy controls inflammation and preserves vision in patients
      with multifocal choroiditis and panuveitis.

PMID- 11825827
TI  - Correction of restricted extraocular muscle motility in surgical management of
      strabismus in graves' ophthalmopathy.
AB  - OBJECTIVE: To compare the success rates for strabismus surgery designed to
      correct limitation of duction with surgery designed to correct deviation in
      patients with Graves' ophthalmopathy. DESIGN: Retrospective nonrandomized
      comparative trial. PARTICIPANTS: One hundred thirty-seven patients with Graves'
      ophthalmopathy who had undergone at least one extraocular muscle surgery were
      divided into two groups: those whose first surgery occurred before June 1997
      (control group) and those whose first surgery occurred in June 1997 or thereafter
      (case group). INTERVENTIONS: Extraocular muscle surgery primarily directed at
      either correcting deviation (control group) or correcting limitation of ductions
      (case group). MAIN OUTCOME MEASURES: Postoperative deviations in the primary
      position were measured in prism diopters 30 to 180 days after surgery. A
      postoperative deviation of less than 5 diopters was considered a successful
      surgical outcome. RESULTS: Patients undergoing strabismus surgery specifically
      designed to correct limitation of duction achieved a 74% success rate compared
      with a 44% success rate in the control group (P < 0.01). Furthermore, the rate of
      reoperation in this group was only 27% compared with 44% in the control group (P
      < 0.04). CONCLUSIONS: Compared with surgery aimed primarily at the correction of
      deviation, extraocular muscle surgery tailored to address restriction of ductions
      in patients with Graves' ophthalmopathy is associated with improved surgical
      success of initial realignment and with a lower rate of reoperation

PMID- 11825828
TI  - Primary banked scleral patch graft in the prevention of exposure of
      hydroxyapatite orbital implants.
AB  - PURPOSE: The most frequently reported complication of hydroxyapatite orbital
      implantation is exposure of the implant, which may result in infection or
      extrusion of the implant. This study describes the use of banked sclera patch
      grafts to prevent implant exposure. DESIGN: A retrospective noncomparative
      interventional case series. PARTICIPANTS: The procedure was performed on 110
      patients over a 2-year period. Hydroxyapatite implantation was performed either
      at the time of enucleation or as a secondary procedure to correct postenucleation
      socket syndrome. INTERVENTION: A banked scleral patch graft from the second eye
      of the same donor was placed over a scleral-wrapped hydroxyapatite implant at the
      time of operation. The case records were reviewed retrospectively. OUTCOME
      MEASURES: The primary outcome measure was the number of patients who developed
      exposure of their hydroxyapatite implant. The number of patients who had a
      postoperative conjunctival wound dehiscence was also recorded. RESULTS: No
      patients developed exposure of the implant. A significant percentage of patients
      developed conjunctival wound dehiscence (33%). Further surgery was not required
      in any of these cases, because the dehiscence spontaneously reconjunctivalized
      over the surface of the scleral patch graft. CONCLUSIONS: Insertion of a banked
      scleral patch graft at the time of hydroxyapatite orbital implantation is an
      effective means of preventing implant exposure, even in more complex cases. It
      thereby reduces the morbidity resulting from the procedure and obviates the need
      for further surgery when there is breakdown of the conjunctival wound
      postoperatively.

PMID- 11825829
TI  - Retained orbital wooden foreign body: a surgical technique and rationale.
AB  - OBJECTIVE: To emphasize the potential complications of a retained orbital wooden
      foreign body (WFB) and the rationale of a surgical technique. DESIGN: Two
      interventional case reports. PARTICIPANTS: Two patients sustained an orbital WFB
      injury. Both patients had ocular complications despite repeated attempts to
      remove the suspected residues. INTERVENTION: Computed tomography and magnetic
      resonance imaging of both patients at different intervals revealed evidence of
      orbital foreign body migration toward the cranium. A surgical technique combing
      transcranial and orbital approaches was used to remove the residues. MAIN OUTCOME
      MEASURES: Preoperative and postoperative vision, proptosis, ocular motility, and
      various ocular symptoms and signs. RESULTS: In both patients, no postoperative
      complications were seen, and all preoperative symptoms and signs were resolved at
      9- and 19-month follow-ups, respectively. CONCLUSIONS: A retained orbital WFB can
      cause early or late complications and is known to have the potential to migrate
      intracranially. In selected patients, a team approach may be the best technique
      to ensure complete removal.

PMID- 11825830
TI  - Role of instrument cleaning and maintenance in the development of diffuse
      lamellar keratitis.
AB  - OBJECTIVE: To determine if instrument cleaning techniques affect the rate of
      diffuse lamellar keratitis (DLK) after laser in situ keratomileusis (LASIK).
      DESIGN: Retrospective case series. PARTICIPANTS: Two hundred ten eyes of 109
      patients. METHODS: A record review was performed of all patients who underwent
      LASIK at the Jules Stein Eye Institute from April 1 through June 24, 1999. During
      the first 6 weeks, the instruments used in LASIK surgery were cleaned according
      to our conventional protocol. At the end of this 6-week period, the cleaning
      protocol was modified and used for a subsequent 6-week period. For each eye
      during the two periods, the status of DLK on the first postoperative day was
      recorded. MAIN OUTCOME MEASURES: Presence of DLK. RESULTS: During the first 6
      week period, 118 eyes of 60 patients underwent LASIK surgery. In the subsequent 6
      weeks, 92 eyes of 49 patients underwent LASIK surgery. The two groups included
      patients with similar demographic background: gender, age, and target correction.
      Diffuse lamellar keratitis was present in 13 of 118 eyes (11%) using our
      conventional protocol. In only 2 of 92 eyes (2%) did DLK develop after the
      protocol was modified. Using the chi-square test, the difference between the two
      groups was statistically significant (P = 0.01). CONCLUSIONS: Diffuse lamellar
      keratitis is a fairly uncommon phenomenon after LASIK surgery. Although the cause
      remains to be elucidated, these results demonstrated a reduced incidence of DLK
      associated with alteration of cleaning procedures and a decrease in stagnant
      instrument cleaning fluids. The authors recommend that refractive centers avoid
      the use of stagnant fluids in their instrument cleaning and sterilizing protocols
      to minimize the occurrence of DLK outbreaks.

PMID- 11825832
TI  - Validation of the pulmonary score: an asthma severity score for children.
AB  - OBJECTIVES: In the absence of a validated "user-friendly" method of scoring
      asthma severity, the authors derived the pulmonary score (PS). The purpose of
      this study was to begin validation trials of the PS by comparing it with the peak
      expiratory flow rate (PEFR). METHODS: The study enrolled a convenience sample of
      children, aged 5-17 years, who came to the emergency department (ED) for
      treatment of an acute asthma exacerbation. The PEFR (best of three attempts) and
      the PS were measured before and after the first albuterol treatment by a
      physician and a nurse from a pool of 45 trained observers. The PS includes
      respiratory rate, wheezing, and retractions, each rated on a 0-3 scale.
      Decreasing PS and increasing PEFR indicate clinical improvement. Pre- and post
      treatment PEFRs and PSs were compared using paired t-tests to establish construct
      validity. Correlation of pre- and post-treatment PSs with PEFRs was measured to
      establish criterion validity. RESULTS: Forty-six subjects completed the study.
      Mean percent predicted PEFR improved after treatment by 20.7% (p = 0.0001), and
      mean PS by 1.5 for nursing-obtained scores (p < 0.0001) and 1.9 for physician
      obtained scores (p < 0.0001). Pre- and post-treatment PSs were significantly
      correlated with PEFRs. Correlations for the nursing-obtained scores were pre
      treatment r = -0.57 (p = 0.0003) and post-treatment r = -0.67 (p = 0.0001), and
      for the physician-obtained scores were pre-treatment r = -0.44 (p = 0.003) and
      post-treatment r = -0.56 (p = 0.0001). The pre-treatment interrater reliability
      was 0.62 and the post-treatment was 0.53. CONCLUSIONS: These data support the
      construct and criterion validities of the PS as a measure of asthma severity
      among children in the ED. The PS is a practical substitute to estimate airway
      obstruction in children who are too young or too sick to obtain PEFRs.

PMID- 11825833
TI  - Mild hypothermia induced before cardiac arrest reduces brain edema formation in
      rats.
AB  - OBJECTIVES: The mechanisms by which hypothermia improves cardiac arrest (CA)
      induced brain damage are unclear. The authors hypothesized that mild hypothermia
      induced before CA attenuates brain edema formation by preventing neutrophil
      mediated dysfunction of the endothelial cell junction proteins. METHODS: Eighteen
      rats were randomized to normal control surgery (group 1, n = 6), normothermic
      (37.5 degrees C) CA (group 2, n = 6), or hypothermic (34 degrees C) CA (group 3,
      n = 6). Hypothermia was induced with external cooling before CA in group 3.
      Cardiac arrest was induced by 8 minutes of asphyxiation. Brain edema was
      determined by wet-to-dry weight ratio and cerebral spinal fluid pressure (CSFP).
      Brain neutrophil content was determined by myeloperoxidase (MPO) activity, and
      occludin degradation was assessed by western blotting. RESULTS: Normothermic CA
      significantly increased brain wet-to-dry weight ratio from 4.52 +/- 0.04 in group
      1 to 4.80 +/- 0.04 in group 2 (p = 0.0003) and CSFP from 3.6 +/- 0.9 in group 1
      to 8.9 +/- 0.9 mm Hg in group 2 (p = 0.004). Mild hypothermia before CA in group
      3 significantly reduced brain wet-to-dry weight ratio (4.68 +/- 0.03, p = 0.008
      vs. group 2) and CSFP (3.8 +/- 0.5 mm Hg, p = 0.004 vs. group 2). Cardiac arrest
      increased brain MPO from 0.07 +/- 0.025 in group 1 to 0.16 +/- 0.02 units/gram
      brain weight in group 2 (p = 0.006) that was not decreased by hypothermia before
      CA (0.12 +/- 0.02 in group 3 (p = 0.07 vs. group 2). There was no occludin
      proteolysis in any group. CONCLUSIONS: Mild hypothermia before CA decreases CA
      induced brain edema. The hypothermia-elicited reduction in brain edema does not
      appear to be neutrophil-dependent and the early brain edema formation may not
      involve the proteolysis of occludin.

PMID- 11825835
TI  - Shock index in the first trimester of pregnancy and its relationship to ruptured
      ectopic pregnancy.
AB  - The shock index (SI), the ratio of heart rate to systolic blood pressure, has
      been reported to be a useful tool in the evaluation of trauma patients presenting
      to the emergency department (ED). OBJECTIVES: To determine the range of values
      for SI seen in first-trimester patients presenting to the ED, and to estimate the
      ability of the SI to predict ruptured ectopic pregnancy (EP). METHODS: This was a
      prospective cohort study enrolling all patients in the first trimester of
      pregnancy presenting to the ED with abdominal pain and/or vaginal bleeding.
      Patients had a SI calculated based on their presenting vital signs, and were
      followed longitudinally to determine a final diagnosis. Ectopic pregnancies were
      categorized based on surgical pathology. Mean levels for SI were determined for
      each group, and ruptured EPs were compared with all other pregnancies using a
      receiver operating characteristic (ROC) curve. RESULTS: The study enrolled 280
      patients, 24 ruptured EPs, 28 unruptured EPs, and 228 non-EPs. The means for SI
      were 0.67 (95% CI = 0.65 to 0.68) for non-EPs, 0.64 (95% CI = 0.61 to 0.67) for
      unruptured EPs, and 0.84 (95% CI = 0.77 to 0.9) for ruptured EPs. The ROC curve
      for SI, heart rate, mean arterial pressure, and systolic blood pressure
      demonstrated areas under the curve (AUCs) of 0.84 (95% CI = 0.78 to 0.88), 0.74
      (95% CI = 0.67 to 0.79), 0.63 (95% CI = 0.67 to 0.79), and 0.70 (95% CI = 0.64 to
      0.77), respectively. CONCLUSIONS: The range of values for SI for patients being
      evaluated for pain and/or vaginal bleeding within the first trimester of
      pregnancy, who do not have a ruptured EP, are within the previously reported
      range of 0.5-0.7 for nonpregnant patients. A SI > 0.85 made the diagnosis of
      ruptured EP 15.0 (95% CI = 5.6 to 40.4) times more likely. This study suggests
      that SI could impact directly on the diagnostic and therapeutic course of the
      patient.

PMID- 11825836
TI  - The Relationship among depressive and alcoholic symptoms and aggressive behavior
      in adult male emergency department patients.
AB  - OBJECTIVE: To determine the extent to which depressive and alcoholic symptoms are
      related to aggressiveness in male emergency department (ED) patients. METHODS: A
      cross-sectional survey design was conducted in a Midwest urban ED. A convenience
      sample of 302 noncritical male patients completed the survey. Self-reported
      aggressiveness, anger problems, Zung depressive symptoms, CAGE alcoholic
      dependence, and demographics were collected. A conceptual causal model was tested
      with structural equation (SEQ) modeling. Regression analyses examined the extent
      to which the Zung scale, CAGE inventory, and demographics explained
      aggressiveness. RESULTS: The SEQ modeling found that both depressive and
      alcoholic symptoms linked significantly to aggressiveness. Depressive symptoms
      linked three times more strongly than alcoholic symptoms to aggressiveness. Model
      fit statistics suggested that depressive and alcoholic symptoms are plausible
      causal factors for male aggressiveness. Regression analyses revealed that four
      items from the Zung scale (irritable, can't sleep, "better off dead," indecisive)
      and two items from the CAGE inventory (annoyed when criticized about drinking,
      need to cut down) explained aggressiveness. CONCLUSIONS: In this urban ED
      population, depressive symptoms linked to aggressiveness three times more
      strongly than alcoholic symptoms. An abbreviated screening tool that could be
      used in EDs incorporating Zung and CAGE items may identify males who would
      benefit from further evaluation for depression, alcoholism, and aggressive
      behavior.

PMID- 11825838
TI  - Utilization of the Ottawa ankle rules by nurses in a pediatric emergency
      department.
AB  - OBJECTIVES: To determine the ability of pediatric emergency department (ED)
      nurses to accurately apply the Ottawa Ankle Rules (OAR) and to evaluate whether
      the rate of negative ankle radiographs can be reduced by incorporating the OAR
      into an existing collaborative practice protocol (CPP). METHODS: The authors' ED
      currently uses a CPP in which patients with ankle pain, swelling, deformity, or
      decreased range of motion on primary nursing assessment undergo radiography prior
      to physician evaluation. A cross-sectional study was conducted between June and
      November 2000. Patients aged 5-19 years with an ankle injury who met at least one
      of the CPP criteria were eligible for enrollment. The OAR were applied by the
      primary nurse after initial assessment. Ankle radiographs were ordered for all
      enrolled patients. The interobserver variability between nurses was evaluated on
      a random sample. RESULTS: One hundred ninety subjects were enrolled in the study.
      The OAR were correctly interpreted by nurses in 98.4% of subjects. Agreement on
      the interobserver reliability sample was 100%. Of the 185 subjects, 31 (16.8%)
      had positive radiographs. Positive OAR results were noted in 30 of 31 subjects
      with positive radiographs. The sensitivity of the OAR was 97% (95% CI = 0.82 to
      0.99) with a specificity of 25% (95% CI = 0.18 to 032). Use of the OAR would have
      reduced the radiography rate by 21%. CONCLUSIONS: Trained nurses can accurately
      apply and interpret the OAR. The incorporation of the OAR into the nursing
      assessment of children with acute ankle injuries may reduce the number of
      radiographs ordered.

PMID- 11825839
TI  - An innovative strategy for conducting clinical research: the academic associate
      program.
AB  - Performance of high-quality clinical research usually requires procurement of
      substantial funding to support and sustain the research infrastructure. The
      authors have developed a program to support a research infrastructure that
      minimizes financial start-up costs and maximizes productivity of clinical
      educator faculty with limited protected time. The program integrates clinical
      research with undergraduate education. The authors report the experience with the
      academic associate program at two academic institutions. They describe the
      program, provide measures of program success, and discuss potential methods for
      other institutions to initiate similar programs. Similar programs can be
      developed in a variety of outpatient and inpatient settings allowing the
      performance of high-quality clinical research in a time-efficient and cost
      effective manner.

PMID- 11825840
TI  - Assessment of emergency medicine residents' computer knowledge and computer
      skills: time for an upgrade?
AB  - OBJECTIVE: To describe emergency medicine residents' (EMRs') personal computer
      (PC) use and educational needs and to compare their perceived and actual PC
      skills. METHODS: This was a prospective, cross-sectional study. Subjects were all
      EMRs at seven midwestern Accreditation Council for Graduate Medical Education
      (ACGME) residency programs. The EMRs completed a questionnaire about their PC use
      and ability to perform 23 tasks derived from two national retail-training
      programs. The tasks covered word processing, slide making, and Internet use. The
      EMRs then took a three-part test performing the skills in the questionnaire. Two
      independent raters scored the tests. Frequencies with 95% confidence intervals
      (95% CIs) were calculated for categorical data. Positive and negative predictive
      values were used to report information comparing residents' performance with
      their self-assessment of skills. Cohen's kappa was used to test agreement between
      raters. RESULTS: One hundred twenty-four of 158 (79%) eligible EMRs participated.
      Since not all participants engaged in all parts of the study, the sample size
      varies between 121 and 124. One hundred one of 122 (83%; 95% CI = 75 to 89) owned
      a PC. The EMRs use home PCs a mean of 3.8 hours/week for physician duties and use
      residency PCs 1.9 hours/week (range 0-20). Ninety-six of 122 (79%; 95% CI = 70 to
      86) EMRs reported no formal PC training during residency. Thirty-five percent
      (43/122; 95% CI = 27 to 44) passed the word-processing test and 50% (62/123; 95%
      CI = 41 to 60) passed the slide-making test. Reasons for failure were because of
      errors and not having a presentable product. Thirty-eight of 122 (31%; 95% CI =
      23 to 40) failed the literature search, including 33 who said they could perform
      it. One hundred fifteen of 123 (94%; 95% CI = 88 to 98) EMRs were able to find an
      Internet address, including ten who stated they could not. Twenty-one percent of
      the residents who attempted any test (26/124; 95% CI = 14 to 29) passed all three
      tests. There was no association between year of training and success on the tests
      (p = 0.374). Thirty-seven of 115 (32%; 95% CI = 24 to 42) EMRs said they had
      insufficient PC training to meet their physician needs. CONCLUSIONS: Emergency
      medicine residents have much access to computer technology and possess some
      computer skills; however, many are unable to produce a usable product or conduct
      a literature search. Emergency medicine residents have not had sufficient
      computer training prior to residency. The computer skills of EMRs should be
      assessed through skills testing rather than self-assessment, and computer
      training during residency should be improved.

PMID- 11825841
TI  - Predictors of genitorectal injury in female victims of suspected sexual assault.
AB  - OBJECTIVE: Legal decisions in sexual assault cases often hinge on the presence or
      absence of genitorectal injury. Unfortunately, the forensic literature does not
      explain why some victims sustain genitorectal injury and others do not. This
      study explores possible predictors of genitorectal injury in adult female sexual
      assault victims. METHODS: This retrospective cross-sectional analysis forms the
      derivation set for a larger planned prospective analysis. The authors extracted
      data describing consecutive female sexual assault victims who met inclusion
      criteria between July 1995 and July 1998. Exclusion criteria included male sex,
      lack of estrogen in females, consensual intercourse within the previous 72 hours,
      and lack of penetration during the assault. The authors explored associations
      between genitorectal injury and seven demographic variables, nine assault
      characteristics, and the time between assault and exam or postcoital interval
      (PCI). Variables thought to be predictive were incorporated into a logistic
      regression model. RESULTS: Five hundred forty-eight sexual assault victims were
      seen during the study time period; 209 of these met the inclusion criteria.
      Logistic regression controlling for important covariates showed an increase risk
      of genitorectal injury with a PCI < 24 hours (OR 7.47, 95% CI = 1.78 to 31.35),
      physical/verbal resistance (OR 5.96, 95% CI = 1.21 to 29.36), rectal penetration
      (OR 7.47, 95% CI = 1.05 to 53.07), and greater than high school education (OR
      7.13, 95% CI = 1.03 to 49.65). CONCLUSIONS: This study presents an important
      first look at variables that may predict genitorectal injury in sexual assault
      victims. Future studies that examine more data are needed to corroborate this
      preliminary derivation set analysis.

PMID- 11825842
TI  - Clinical pearls: altered mental status and a rash.

PMID- 11825843
TI  - Should parents be present during emergency department procedures on children, and
      who should make that decision? A survey of emergency physician and nurse
      attitudes.
AB  - OBJECTIVE: To survey physician and nurse attitudes regarding parental presence
      during painful procedures on children performed in the emergency department (ED)
      and who should make that decision. METHODS: The design was an anonymous written
      survey consisting of six clinical scenarios distributed to all staff and resident
      physicians and nurses in ten EDs at institutions in the United States routinely
      caring for children. Participants were asked whether parents should remain with
      children undergoing intravenous (IV) placement, laceration repair, lumbar
      puncture, conscious sedation, major resuscitation, and major resuscitation with
      death. They also were asked who should make the decision. RESULTS: The percentage
      of physicians who responded that parents should be present was 91.3% for
      peripheral IV start, 93.3% for laceration repair, 65.7% for lumbar puncture,
      83.1% for conscious sedation, 31.9% for major resuscitation, and 35.6% for major
      resuscitation where death was likely. The percentage of nurses who responded that
      parents should be present was 86.8% for peripheral IV start, 89.6% for laceration
      repair, 55.0% for lumbar puncture, 74.9% for conscious sedation, 41.4% for major
      resuscitation, and 54.3% for major resuscitation where death was likely. In 64.8%
      of the completed surveys, the physicians indicated that they alone or in
      conjunction with a parent should make the decision. In 61.5% of the completed
      surveys, the nurses indicated that they should be involved in the decision.
      CONCLUSIONS: A majority of emergency physicians and nurses indicated parents
      should be present for some invasive pediatric procedures. However, as the
      invasiveness of the pediatric procedures increased, fewer physicians and nurses
      believed that parents should be present.

PMID- 11825844
TI  - Clinicopathological conference: a 73-year-old man with shock, stroke, and
      cyanotic extremities.

PMID- 11825845
TI  - Observation medicine in emergency medicine residency programs.
AB  - OBJECTIVE: To evaluate observation unit (OU) prevalence, emergency medicine (EM)
      resident exposure in observation medicine (OM), EM faculty/residency director
      (RD) OM training, and RD attitudes toward OM. METHODS: Information was obtained
      from residency programs by telephone during a four-month period. RESULTS: Survey
      respondents indicated that 36.1% have OUs and 44.9% plan to have an OU.
      Observation medicine resources include textbooks 32.0%, articles 45.9%, lectures
      36.9%, fellowships 2.5%, and research 26.2%. Observation medicine patient care
      occurs: 1) during residency: 25.4% of RDs, 11.3% of entire faculty; 2) as an
      attending: 45.1% of RDs. CONCLUSIONS: Nearly two-thirds of EM programs have or
      are planning an OU. Resources are lagging behind. This survey describes current
      OM education strategies to teach OM.

PMID- 11825846
TI  - A fifth mechanism of lightning injury.
AB  - The four classic electrical mechanisms of lightning injury cannot account for all
      injuries. A fifth mechanism, injury by a weak upward streamer that does not
      become part of a completed lightning channel, has long been postulated in the
      engineering literature by lightning researchers. This paper reports a case of
      death where injury from a weak upward streamer is strongly suspected following
      forensic investigation. Neither high voltage nor any of the previously accepted
      mechanisms of lightning injury can explain this incident.

PMID- 11825847
TI  - Error in an emergency medicine textbook: isopropyl alcohol toxicity.

PMID- 11825849
TI  - Ophthalmic involvement in the fetal alcohol syndrome: clinical and animal model
      studies.
AB  - The fetal alcohol syndrome (FAS) is caused by maternal alcohol misuse during
      pregnancy and is characterized by pre- and postnatal growth retardation, central
      nervous system anomalies and a wide spectrum of malformations, the most typical
      being the craniofacial features. The eye is a sensitive indicator of the adverse
      effects of environmental agents, and the ocular abnormalities observed in
      children with FAS indicate that the developing eye is particularly affected by
      alcohol. The external signs include short palpebral fissures, telecanthus,
      epicanthus, blepharoptosis, microphthalmos and strabismus. Within the eyes, the
      signs and symptoms most commonly detected are optic nerve hypoplasia, increased
      tortuosity of the retinal vessels and impaired vision. Experimental models of
      FAS, closely reproducing characteristics of human FAS, have contributed to our
      understanding of the cellular and molecular basis of the action of alcohol in the
      developing visual system. As there is such a high frequency of eye signs and
      symptoms in FAS, an ophthalmological examination is important when making the
      diagnosis, as well as in the management of the disorder. Current knowledge of
      ophthalmological involvement in FAS in humans is presented, as well as a review
      of findings using animal models specially designed for studying ocular
      developmental changes induced by alcohol.

PMID- 11825850
TI  - Different blood acetaldehyde concentration following ethanol administration in a
      newly developed high alcohol preference and low alcohol preference rat model
      system.
AB  - A significant difference in blood-acetaldehyde concentration was observed between
      high alcohol-preference (HAP) rats and low alcohol-preference (LAP) rats, newly
      developed different alcohol preference lines. This difference of acetaldehyde
      accumulation may be due to cytosolic aldehyde dehydrogenase (ALDH1) polymorphism,
      which has been reported previously. As the doses of ethanol we employed are
      higher than that of voluntary drinking, there may be little direct relationship
      between acetaldehyde accumulation and alcohol preference. We suggest therefore
      that the ALDH1 polymorphism is associated with alcohol preference in HAP/LAP
      lines through some other unidentified mechanism.

PMID- 11825851
TI  - Chronic ethanol consumption results in deficient bone repair in rats.
AB  - There is evidence that ethanol inhibits osteoblast function and that chronic
      ethanol consumption induces systemic bone loss and increases the risk of fracture
      in humans. The purpose of the present study was to determine whether chronic
      ethanol consumption also compromises the healing of injured bone. Male Sprague
      Dawley rats, 8-10 weeks old, were placed into four feeding groups: group A
      received ethanol (36% of calories) as part of a liquid diet; group B was pair-fed
      to group A and received an isocaloric control diet containing maltodextrin; group
      C was fed the AIN-93M standard semi-purified liquid diet ad libitum; group D was
      fed the same ethanol diet as group A before bone injury, but after surgery (see
      below) these rats were given isocaloric control diet ad libitum. After 6 weeks on
      their respective diets, a bone repair model was surgically created at the
      midshaft in both fibulae of each rat. Seven weeks after injury the animals were
      euthanized and bone healing was evaluated by determining rigidity of the fibula
      by three-point bending, flexural modulus of the repair tissue and mineral content
      of the repair tissue. Rigidity of fibula in ethanol-fed rats and their pair-fed
      controls (groups A and B) were respectively 48 and 47% lower than in group C.
      Flexural modulus of the repair tissue in ethanol-fed rats had a 55% (P = 0.046)
      deficiency compared with their pair-fed controls. The mineral contents in groups
      A and B were respectively 16 and 13% lower than in group C. There were no
      significant differences in the results between groups C and D. Thus, the outcome
      of bone repair in ethanol-fed rats was deficient compared with rats receiving a
      standard maintenance diet. The repair tissue in ethanol-fed rats was mechanically
      inferior to that in pair-fed controls. This deficiency could not be attributed to
      the reduced food consumption of these animals. On the other hand, the restoration
      of normal bone healing in group D cannot be attributed solely to the cessation of
      ethanol feeding after bone injury because of the increased food consumption
      during this period.

PMID- 11825852
TI  - Effects of alcohol on bone mineral and mechanical properties of bone in male
      rats.
AB  - The effect of ethanol on bone mineral is poorly understood. In this study we have
      investigated whether ethanol affects bone mineral content (BMC), bone mineral
      density (BMD) measured by dual energy X-ray absorptiometry, and the mechanical
      properties of the tibia and femora in male Sprague-Dawley rats without
      histopathological signs of liver disease or nutritional deficit. Thirty-five male
      rats were fed a liquid diet containing 15% ethanol and glucose. An equivalent iso
      volumetric amount of glucose-containing liquid was fed to the controls (n = 35).
      After an initial difference in weight, we found no difference in weight gain from
      week 1 to week 6. All animals were killed at 6 weeks. We found no evidence of
      ethanol-induced liver disease in a histopathological evaluation. The BMD and BMC
      were found to be lower in the ethanol group. No differences between the groups
      were found in the mechanical properties or in the length and size of the femora.
      We suggest that alcohol may have a toxic effect on bone in male rats known not to
      suffer from any histopathological hepatic lesions.

PMID- 11825853
TI  - Bile salts modulate chronic ethanol-induced hepatotoxicity.
AB  - This study tested the hypothesis that chronic ethanol-induced injury in rats may
      be modified by the hydrophobicity of the bile acid pool. The supplementation to
      chronic ethanol feeding (28 days) with chenodeoxycholate, a hydrophobic bile
      salt, aggravated steatosis (accumulation of triacylglycerols and cholesterol
      esters), lipoperoxidation and cytolysis (expressed as elevations of activities of
      aspartate aminotransferase and glutamate dehydrogenase), while the addition of
      ursodeoxycholic acid, a hydrophilic bile salt, alleviated ethanol-induced hepatic
      alterations. Furthermore, our data show that ursodeoxycholic acid still exerts
      its beneficial effects in a model of more severe hepatic intoxication induced by
      the co-administration of ethanol and chenodeoxycholic acid. The hepato-protective
      effect observed appears to be independent of the choleretic properties of
      ursodeoxycholic acid and may be due partly to the capacity of the bile acid to
      preserve mitochondria.

PMID- 11825854
TI  - Influence of prenatal alcohol exposure on myocardial contractile function in
      adult rat hearts: role of intracellular calcium and apoptosis.
AB  - To assess the teratogenic action of ethanol on cardiac contractile function in
      offspring exposed to ethanol in utero, pregnant Sprague-Dawley rats were fed with
      ethanol during gestation. Left-ventricular papillary muscles and myocytes were
      isolated from the offspring of the ethanol-ingesting and control pregnant rats.
      Mechanical parameters measured were peak tension development (PTD, indicating the
      myocardial force-generating capacity), peak cell shortening (PS), time-to-PTD/PS
      (TPT/TPS), time-to-90% relaxation/re-lengthening (RT(90)/TR(90)), and maximal
      velocities of contraction/shortening and relaxation/re-lengthening (+/- VT and +/
      dL/dt). Intracellular Ca(2+) levels and apoptosis were evaluated with fura-2
      fluorescent dye and Caspase-3 activation assay, respectively. Offspring of the
      ethanol group displayed decreased heart weight associated with comparable body,
      liver and kidney weight, and papillary muscle weight/size, compared to the
      control group. However, prenatal ethanol exposure depressed myocardial PTD and +/
      VT. The myocardium from the ethanol group also exhibited slightly but
      significantly shortened TPT, accompanied with normal RT(90). Muscles from both
      groups exhibited comparable responses to post-rest potentiation, increasing
      extracellular Ca(2+) concentration, noradrenaline and acute ethanol challenge.
      Ventricular myocytes from both the control and ethanol groups possessed similar
      PS, TPS, TR(90) and +/- dL/dt. Both resting and peak intracellular Ca(2+) levels
      were elevated in myocytes from the ethanol group. Additionally, acute ethanol
      application depressed caffeine-induced intracellular Ca(2+) rise in myocytes from
      both groups. Myocytes from the ethanol group displayed an enhanced Caspase-3
      activation, compared to control myocytes. These results suggest that prenatal
      ethanol exposure alters myocardial contractile function and may contribute to the
      development of postnatal cardiac dysfunction through, in part, increased
      intracellular Ca(2+) loading and apoptosis.

PMID- 11825855
TI  - Early intervention for problem drinkers: readiness to participate among general
      practitioners and nurses in Swedish primary health care.
AB  - An exploration was made of attitudes and practices of general practitioners (GPs)
      and nurses concerning early identification of, and intervention for, alcohol
      related problems. Sixty-five GPs and 141 nurses in 19 primary health centres in a
      county in southern Sweden answered a 28-item questionnaire before implementation
      of an intervention programme. The questionnaire covered experiences with patients
      with alcohol-related health problems, knowledge and perceived capacity concerning
      early identification and intervention, attitudes towards the role of primary care
      staff in early identification and intervention and current intervention methods
      in use at the health centre. Self-reported frequency of asking about alcohol use
      was higher among GPs than nurses. Both groups reported more frequently asking
      about alcohol consumption in cases where they believed that the health status was
      influenced by alcohol. For both professions, knowledge and skills concerning
      identification were rated as better understood than that concerning intervention
      methods. Nurses rated their knowledge and skills less confidently than GPs. The
      overall attitude was fairly positive towards early identification and
      intervention, but nurses were more worried than GPs that patients would react
      negatively to questions about alcohol. Attitudes, self-rated capacity, and
      practice were related. The low level of early identification and intervention in
      primary care appears to be related more to insufficient practical skills than to
      attitudes. Nurses appear to be an unexploited resource, in need of training and
      support. Nurses may need to be convinced that an active role does not interfere
      with the nurse-patient relationship. Building teams of GPs and nurses in primary
      care might enhance the dissemination of alcohol prevention into regular practice.

PMID- 11825856
TI  - Hepatocyte proliferation and apoptosis in relation to oxidative damage in alcohol
      related liver disease.
AB  - In alcohol-related liver disease, free radicals play a part in the pathogenesis
      of liver damage and may influence cell turnover. The aims of this study were to
      correlate lipid peroxidation, antioxidant defence and iron metabolism with cell
      proliferation and apoptosis in alcoholic liver injury, and also in comparison
      with virus-related liver disease. In 45 patients [10 with chronic alcoholic liver
      damage (CALD), 24 with HCV-related (HCV) and 11 with HBV-related chronic
      hepatitis (HBV)], and 10 control subjects, we investigated serum ferritin, liver
      tissue iron, cysteine, reduced/oxidized glutathione, malondialdehyde, histology
      with hepatocyte proliferation and the apoptotic index. Ferritin, iron levels and
      malondialdehyde were significantly higher in HCV and CALD than in HBV, and
      malondialdehyde correlated with both iron and ferritin. Glutathione levels were
      significantly lower in CALD than in HCV, HBV and control subjects, whereas
      cysteine levels were significantly higher. The apoptotic index was slightly lower
      in CALD, with apoptosis occurring more frequently in the centrilobular area,
      while CALD had fewer proliferating hepatocytes, both overall and in the
      periportal and centrilobular areas. This study confirms that chronic alcohol
      intake: (1) induces more peroxidative damage, which correlates with iron loading;
      (2) reduces antioxidant defence, lowering reduced glutathione liver availability;
      (3) induces an accumulation of cysteine, a glutathione precursor/metabolite in
      the liver, probably due to gamma-glutamyltransferase induction; (4) correlates
      with a lesser extent and different distribution of hepatocyte proliferation and
      apoptosis than in viral liver damage. This last finding may explain the different
      types of liver cirrhosis deriving from alcoholic liver damage and the lower
      cancer risk.

PMID- 11825857
TI  - Alcohol-induced alterations in blood and erythrocyte membrane in diabetics.
AB  - Three groups consisting of 12 volunteers each, of alcoholic type 2 diabetics (non
      insulin-dependent diabetes mellitus, NIDDM), non-alcoholic type 2 diabetics
      (NIDDM) and controls (teetotallers) were selected for assessing changes in lipids
      of plasma and erythrocyte membranes. Significant changes in cholesterol and
      phospholipids were observed in alcoholic diabetics suggesting a regulatory
      compensatory mechanism to resist the fluidizing action of ethanol as well as
      rigidification of erythrocyte membrane. A significant increase in lipid
      peroxidation of erythrocytes was observed, indicating the damage associated with
      disrupted organization, structure and function of membranes in alcoholic
      diabetics.

PMID- 11825858
TI  - Family structure, parent-child relationships, and alcohol and other drug use
      among teenagers in France and the United Kingdom.
AB  - This paper compares samples of 15-16-year-olds from the UK and France on their
      usage of alcohol, tobacco and illicit drugs and also seeks to describe the
      associations between alcohol and other drug use with "family variables" within
      the two countries. Compared to UK adolescents, French adolescents showed a
      slightly higher rate of cigarette smoking, were almost identical on cannabis use,
      rather lower on the use of other illicit drugs and very considerably lower on
      alcohol use. Family variables were related to substance use. In the two
      countries, children from non-intact families, those who were not satisfied with
      their relationships with their father or mother and those who were less closely
      monitored, were more likely to be heavy substance users than other students.
      Logistic regressions showed that parental knowledge of the whereabouts of their
      offspring on Saturday evenings was the strongest factor, in both countries, that
      family structure is frequently still significant in the UK, and that paternal
      relationships are highly significant among French students. Differences in
      national drinking culture, urbanization and parental practices are discussed in
      an attempt to interpret some of these findings.

PMID- 11825859
TI  - The FAST Alcohol Screening Test.
AB  - Using the Alcohol Use Disorders Identification Test (AUDIT) as the gold standard,
      the Fast Alcohol Screening Test (FAST) was developed for use in busy medical
      settings. AUDIT questionnaires were completed by 666 patients in two London
      accident & emergency (A&E) departments. Using a principal components analysis, as
      well as sensitivity and specificity indices, a two-stage screening test was
      developed, using four of the AUDIT items. The first stage involved one item that
      identified >50% of patients as either hazardous or non-hazardous drinkers. The
      second stage made use of the other three items to categorize the rest. The
      performance of this four-item questionnaire was then tested across a range of
      settings. Opportunistic samples of 100 patients completed AUDIT questionnaires in
      each of the following National Health Service settings: A&E department, fracture
      clinic, primary health centre and a dental hospital. It was concluded that the
      four-item FAST questionnaire had good sensitivity and specificity, across a range
      of settings, when the AUDIT score was used as the gold standard. The FAST
      questionnaire is quick to administer, since >50% of patients are categorized
      using just one question.

PMID- 11825860
TI  - Double-blind controlled trial of gamma-hydroxybutyrate and clomethiazole in the
      treatment of alcohol withdrawal.
AB  - The aim of this double-blind, comparative study was to assess the efficacy and
      safety of gamma-hydroxybutyrate (GHB) in ameliorating the symptoms of alcohol
      withdrawal. Newly admitted alcohol-dependent patients (n = 98) were randomized to
      receive either clomethiazole 1000 mg daily (CLO group) (n = 33), or 50 mg GHB/kg
      body wt (n = 33) or 100 mg GHB/kg body wt (n = 32). This dose was administered
      for 5 days, halved on day 6, and on days 7 and 8 only placebo was given. As CLO
      is available as capsules and GHB as syrup, a double-dummy method was used to try
      to ensure blindness. The groups were matched in terms of baseline demographic and
      alcohol-related variables. There was no difference between the three treatments
      in ratings of alcohol withdrawal symptoms nor requests for additional medication.
      After tapering off the active medication, there was no increase in withdrawal
      symptoms, indicating that physical tolerance did not develop to either GHB or CLO
      within the 5-day treatment period. The most frequently reported side-effect of
      GHB was transient vertigo, particularly after the evening double dose.

PMID- 11825861
TI  - Teenage alcohol and intoxication debut: the impact of family socialization
      factors, living area and participation in organized sports.
AB  - The aim of the present study was to examine the age distribution of alcohol and
      intoxication debut and factors associated with this among a representative sample
      of Norwegian teenagers. A sample of 3368 teenagers aged 12-18 years was recruited
      from 34 Norwegian secondary schools to complete an 87-item questionnaire under
      examination conditions; 5.2% (168/3239) reported drinking alcohol for the first
      time when 10 years or younger, 25.2% (816/3239) when they were 13 years or
      younger and 60.1% (1948/3239) when 16 years or younger, with 39.9% having never
      drunk alcohol; 1.3% (44/3239) were first intoxicated by 10 years or younger,
      12.8% (418/3239) when 13 years or younger and 37.5% (1649/3239) when 16 years or
      younger. Pupils with early alcohol or intoxication debut (<14 years) tended to
      come from single-parent families, from cities, experienced less family support
      and a more highly organized family life, reported more frequent peer and parental
      drinking, and did not participate in sports. They also showed a substantially
      elevated total yearly current alcohol consumption, compared to the group with
      alcohol debut at 14 years or later (8.1 and 2.5 l pure alcohol, respectively).
      Poor family support but high family organization, living in single-parent
      families and in cities, and more frequent parental and peer drinking are
      associated with early alcohol debut, whereas participation in organized sport
      activities may delay drinking and intoxication debut in teenagers. Sports
      organizations should be included in drinking prevention programmes.

PMID- 11825862
TI  - Concentrations of lipopolysaccharide-binding protein, bactericidal/permeability
      increasing protein, soluble CD14 and plasma lipids in relation to endotoxaemia in
      patients with alcoholic liver disease.
AB  - There is increasing evidence that gut leakage in persons with chronic alcohol
      misuse leads to endotoxaemia, which might contribute to the development of
      alcoholic hepatitis or cirrhosis. In addition, it was recently shown that the
      endotoxin-binding capacity of whole blood is reduced in these patients. To
      analyse this phenomenon, we measured the concentration of functionally important
      endotoxin-binding plasma components which modify the action of endotoxin. In
      patients with minimal (n = 10), intermediate (n = 9), and cirrhotic alcoholic
      liver disease (n = 11), and healthy controls (n = 11), plasma endotoxin was
      determined in a limulus assay. The concentration of lipoproteins was assessed by
      measuring apolipoproteins, the other factors were directly measured in
      immunoassays. In the entire group of alcoholics, endotoxin and the concentration
      of binding factors that are involved in the action of endotoxin on its target
      cells (LPS-binding protein and sCD14) were increased. Endotoxin antagonists, such
      as bactericidal/permeability-increasing protein and high-density lipoprotein,
      were increased in the pre-cirrhotic stages, whereas a significant reduction of
      the latter was observed in cirrhosis. Low-density lipoprotein remained unchanged.
      The elevation of binding factors in the pre-cirrhotic stages of alcoholic liver
      disease might attenuate the effects of endotoxaemia, whereas in cirrhosis the
      reduction of high density lipoprotein, to which large quantities of endotoxin
      bind, may contribute to its pro-inflammatory effects.

PMID- 11825863
TI  - Moderate alcohol intake in pregnancy and the risk of spontaneous abortion.
AB  - Women attending routine antenatal care at Aarhus University Hospital, Denmark,
      from 1989 to 1996 were eligible for this cohort study on the association between
      alcohol intake in pregnancy and the risk of spontaneous abortion. We included 24
      679 singleton pregnancies in the study. We used Cox regression analyses with
      delayed entry for the analyses. We found an increased risk of spontaneous
      abortion in the first trimester (7-11 completed weeks of gestation) for women
      consuming > or =5 drinks/week. We found no association between alcohol intake and
      spontaneous abortion during the second trimester. Common methodological problems
      in relation to studies on spontaneous abortions are discussed, as are problems
      with possible under-reporting of alcohol consumption. We conclude that women
      consuming > or =5 drinks/week are at increased risk of first trimester
      spontaneous abortion.

PMID- 11825864
TI  - Reliability and validity of the Dutch version of the Readiness to Change
      Questionnaire.
AB  - The aim of the present study was to evaluate the psychometric properties of the
      Dutch version of the Readiness to Change Questionnaire (RCQ-D). The subjects were
      246 excessive drinkers admitted to an addiction treatment centre and 54 offenders
      convicted of an alcohol-related crime in The Netherlands. The factor structure of
      the RCQ-D for the two samples combined was found to be consistent with the three
      factor structure established for the original RCQ. The reliability of the items
      for each scale was found to be satisfactory. Allocated stage of change showed
      significant differences between the different subsamples. As expected, the scale
      scores for adjacent stages of change showed significantly higher inter
      correlations than the scale scores for non-adjacent stages. Additionally, the
      negatively formulated items from the pre-contemplation scale were reformulated
      positively and their internal consistency tested among the offender sample. The
      positively formulated pre-contemplation items showed a higher alpha value than
      the negatively formulated items. We therefore suggest that the positively
      formulated items should replace the negatively formulated ones.

PMID- 11825865
TI  - Translation problems of the Spanish version of the Readiness to Change
      Questionnaire.

PMID- 11825869
TI  - Insulators: many functions, many mechanisms.

PMID- 11825870
TI  - A specific protein substrate for a deubiquitinating enzyme: Liquid facets is the
      substrate of Fat facets.
AB  - Eukaryotic genomes encode large families of deubiquitinating enzymes (DUBs).
      Genetic data suggest that Fat facets (Faf), a Drosophila DUB essential for
      patterning the compound eye, might have a novel regulatory function; Faf might
      reverse the ubiquitination of a specific substrate, thereby preventing
      proteasomal degradation of that protein. Additional genetic data implicate Liquid
      facets (Lqf), a homolog of the vertebrate endocytic protein epsin, as a candidate
      for the key substrate of Faf. Here, biochemical experiments critical to testing
      this model were performed. The results show definitively that Lqf is the key
      substrate of Faf in the eye; Lqf concentration is Faf-dependent, Lqf is
      ubiquitinated in vivo and deubiquitinated by Faf, and Lqf and Faf interact
      physically.

PMID- 11825871
TI  - Direct induction of T lymphocyte-specific gene expression by the mammalian Notch
      signaling pathway.
AB  - The Notch signaling pathway regulates the commitment and early development of T
      lymphocytes. We studied Notch-mediated induction of the pre-T cell receptor alpha
      (pTa) gene, a T-cell-specific transcriptional target of Notch. The pTa enhancer
      was activated by Notch signaling and contained binding sites for its nuclear
      effector, CSL. Mutation of the CSL-binding sites abolished enhancer induction by
      Notch and delayed the up-regulation of pTa transgene expression during T cell
      lineage commitment. These results show a direct mechanism of stage- and tissue
      specific gene induction by the mammalian Notch/CSL signaling pathway.

PMID- 11825872
TI  - The zinc-finger proto-oncogene Gfi-1b is essential for development of the
      erythroid and megakaryocytic lineages.
AB  - Gfi-1 and Gfi-1b are novel proto-oncogenes identified by retroviral insertional
      mutagenesis. By gene targeting, we establish that Gfi-1b is required for the
      development of two related blood lineages, erythroid and megakaryocytic, in mice.
      Gfi-1b(-/-) embryonic stem cells fail to contribute to red cells of adult
      chimeras. Gfi-1b(-/-) embryos exhibit delayed maturation of primitive
      erythrocytes and subsequently die with failure to produce definitive enucleated
      erythrocytes. The fetal liver of mutant mice contains erythroid and
      megakaryocytic precursors arrested in their development. Myelopoiesis is normal.
      Therefore, Gfi-1b is an essential transcriptional regulator of erythroid and
      megakaryocyte development.

PMID- 11825873
TI  - CD44 anchors the assembly of matrilysin/MMP-7 with heparin-binding epidermal
      growth factor precursor and ErbB4 and regulates female reproductive organ
      remodeling.
AB  - CD44 is a facultative proteoglycan implicated in cell adhesion and trafficking,
      as well as in tumor survival and progression. We demonstrate here that CD44
      heparan sulfate proteoglycan (CD44HSPG) recruits proteolytically active matrix
      metalloproteinase 7 (matrilysin, MMP-7) and heparin-binding epidermal growth
      factor precursor (pro-HB-EGF) to form a complex on the surface of tumor cell
      lines, postpartum uterine and lactating mammary gland epithelium, and uterine
      smooth muscle. The HB-EGF precursor within this complex is processed by MMP-7,
      and the resulting mature HB-EGF engages and activates its receptor, ErbB4,
      leading to, among other events, cell survival. In CD44(-/-) mice, postpartum
      uterine involution is accelerated and maintenance of lactation is impaired. In
      both uterine and mammary epithelia of these mice, MMP-7 localization is altered
      and pro-HB-EGF processing as well as ErbB4 activation are decreased. Our
      observations provide a mechanism for the assembly and function of a cell surface
      complex composed of CD44HSPG, MMP 7, HB-EGF, and ErbB4 that may play an important
      role in the regulation of physiological tissue remodeling.

PMID- 11825874
TI  - Divergent functions of the proneural genes Mash1 and Ngn2 in the specification of
      neuronal subtype identity.
AB  - The neural bHLH genes Mash1 and Ngn2 are expressed in complementary populations
      of neural progenitors in the central and peripheral nervous systems. Here, we
      have systematically compared the activities of the two genes during neural
      development by generating replacement mutations in mice in which the coding
      sequences of Mash1 and Ngn2 were swapped. Using this approach, we demonstrate
      that Mash1 has the capacity to respecify the identity of neuronal populations
      normally derived from Ngn2-expressing progenitors in the dorsal telencephalon and
      ventral spinal cord. In contrast, misexpression of Ngn2 in Mash1-expressing
      progenitors does not result in any overt change in neuronal phenotype. Taken
      together, these results demonstrate that Mash1 and Ngn2 have divergent functions
      in specification of neuronal subtype identity, with Mash1 having the
      characteristics of an instructive determinant whereas Ngn2 functions as a
      permissive factor that must act in combination with other factors to specify
      neuronal phenotypes. Moreover, the ectopic expression of Ngn2 can rescue the
      neurogenesis defects of Mash1 null mutants in the ventral telencephalon and
      sympathetic ganglia but not in the ventral spinal cord and the locus coeruleus,
      indicating that Mash1 contribution to the specification of neuronal fates varies
      greatly in different lineages, presumably depending on the presence of other
      determinants of neuronal identity.

PMID- 11825875
TI  - Pollen tube development and competitive ability are impaired by disruption of a
      Shaker K(+) channel in Arabidopsis.
AB  - Sexual reproduction in plants requires elongation of the pollen tube through the
      transmitting tissues toward the ovary. Tube growth rate is a major determinant of
      pollen competitive ability. We report that a K(+) channel of the Shaker family in
      Arabidopsis, SPIK, plays an important role in pollen tube development. SPIK was
      found to be specifically expressed in pollen. When SPIK was heterologously
      expressed in COS cells, its product formed hyperpolarization-activated K(+)
      channels. Disruption (T-DNA insertion) of the SPIK coding sequence strongly
      affected inwardly rectifying K(+)-channel activity in the pollen-grain plasma
      membrane. Measurements of membrane potential in growing pollen tubes yielded data
      compatible with a contribution of SPIK to K(+) influx. In vitro pollen
      germination assays were performed, revealing that the disruption results in
      impaired pollen tube growth. Analysis of the transmission rate of the disrupted
      allele in the progeny of heterozygous plants revealed a decrease in pollen
      competitive ability, the probability of fertilization by mutant pollen being
      approximately 1.6 times lower than that by wild-type pollen. The whole set of
      data supports the hypothesis that functional expression of SPIK plays a role in
      K(+) uptake in the growing pollen tube, and thereby in tube development and
      pollen competitive ability.

PMID- 11825876
TI  - Intronless homing: site-specific endonuclease SegF of bacteriophage T4 mediates
      localized marker exclusion analogous to homing endonucleases of group I introns.
AB  - All genetic markers from phage T2 are partially excluded from the progeny of
      mixed infections with the related phage T4 (general, or phage exclusion). Several
      loci, including gene 56 of T2, are more dramatically excluded, being present in
      only approximately 1% of the progeny. This phenomenon is referred to as localized
      marker exclusion. Gene 69 is adjacent to gene 56 of T4 but is absent in T2, being
      replaced by completely nonhomologous DNA. We describe SegF, a novel site-specific
      DNA endonuclease encoded by gene 69, which is similar to GIY-YIG homing
      endonucleases of group I introns. Interestingly, SegF preferentially cleaves gene
      56 of T2, both in vitro and in vivo, compared with that of phage T4. Repair of
      the double-strand break (DSB) results in the predominance of T4 genes 56 and segF
      in the progeny, with exclusion of the corresponding T2 sequences. Localized
      exclusion of T2 gene 56 is dependent on full-length SegF and is likely analogous
      to group I intron homing, in which repair of a DSB results in coconversion of
      markers in the flanking DNA. Phage T4 has many optional homing endonuclease genes
      similar to segF, whereas similar endonuclease genes are relatively rare in other
      members of the T-even family of bacteriophages. We propose that the general
      advantage enjoyed by T4 phage, over almost all of its relatives, is a cumulative
      effect of many of these localized events.

PMID- 11825877
TI  - A role for Ddc1 in signaling meiotic double-strand breaks at the pachytene
      checkpoint.
AB  - The pachytene checkpoint prevents meiotic cell cycle progression in response to
      unrepaired recombination intermediates. We show that Ddc1 is required for the
      pachytene checkpoint in Saccharomyces cerevisiae. During meiotic prophase, Ddc1
      localizes to chromosomes and becomes phosphorylated; these events depend on the
      formation and processing of double-strand breaks (DSBs). Ddc1 colocalizes with
      Rad51, a DSB-repair protein, indicating that Ddc1 associates with sites of DSB
      repair. The Rad24 checkpoint protein interacts with Ddc1 and with recombination
      proteins (Sae1, Sae2, Rad57, and Msh5) in the two-hybrid protein system,
      suggesting that Rad24 also functions at DSB sites. Ddc1 phosphorylation and
      localization depend on Rad24 and Mec3, consistent with the hypothesis that Rad24
      loads the Ddc1/Mec3/Rad17 complex onto chromosomes. Phosphorylation of Ddc1
      depends on the meiosis-specific kinase Mek1. In turn, Ddc1 promotes the stable
      association of Mek1 with chromosomes and is required for Mek1-dependent
      phosphorylation of the meiotic chromosomal protein Red1. Ddc1 therefore appears
      to operate in a positive feedback loop that promotes Mek1 function.

PMID- 11825878
TI  - Activation of the JNK pathway during dorsal closure in Drosophila requires the
      mixed lineage kinase, slipper.
AB  - The Jun kinase (JNK) pathway has been characterized for its role in stimulating
      AP-1 activity and for modulating the balance between cell growth and death during
      development, inflammation, and cancer. Six families of mammalian kinases acting
      at the level of JNKKK have emerged as upstream regulators of JNK activity (MLK,
      LZK, TAK, ASK, MEKK, and TPL); however, the specificity underlying which kinase
      is utilized for transducing a distinct signal is poorly understood. In
      Drosophila, JNK signaling plays a central role in dorsal closure, controlling
      cell fate and cell sheet morphogenesis during embryogenesis. Notably, in the fly
      genome, there are single homologs of each of the mammalian JNKKK families. Here,
      we identify mutations in one of those, a mixed lineage kinase, named slipper
      (slpr), and show that it is required for JNK activation during dorsal closure.
      Furthermore, our results show that other putative JNKKKs cannot compensate for
      the loss of slpr function and, thus, may regulate other JNK or MAPK-dependent
      processes.

PMID- 11825880
TI  - The salivary mucin MG1 (MUC5B) carries a repertoire of unique oligosaccharides
      that is large and diverse.
AB  - The high-molecular-mass salivary mucin MG1, one of two major mucins produced by
      human salivary glands, plays an important role in oral health by coating the
      tooth surface and by acting as a bacterial receptor. Here this mucin was purified
      from the submandibular/sublingual saliva of a blood group O individual. The
      presence of MUC5B as the major mucin in this preparation was confirmed by amino
      acid analysis and its reactivity with the monoclonal antibody PAN H2. To
      structurally characterize MG1 carbohydrates the O-glycans were released by
      reductive beta-elimination. Nuclear magnetic resonance spectroscopy of the
      nonfractionated mixture showed that (1) fucose was present in blood group H,
      Le(a), Le(x), Le(b), and Le(y) epitopes; (2) NeuAc was mainly linked alpha 2-3 to
      Gal or alpha 2-6 to GalNAcol; and (3) the major internal structures were core 1
      and core 2 sequences. After this preliminary analysis the released
      oligosaccharides were separated into neutral (56%), sialylated (26%), and
      sulfated (19%) fractions, with an average length of 13, 17, and 41 sugar
      residues, respectively. Gas chromatography-mass spectrometry and matrix-assisted
      laser desorption/ionization time-of-flight mass spectrometry of mixtures of
      neutral and sialylated oligosaccharides revealed at least 62 neutral and 25
      sialylated oligosaccharides consisting of up to 20 monosaccharide residues. These
      results showed that the MG1-derived oligosaccharides were much longer than those
      of MG2, and only a few species were found on both molecules. Thus, these two
      mucins create an enormous repertoire of potential binding sites for
      microorganisms at one of the major portals where infectious organisms enter the
      body.

PMID- 11825879
TI  - mom identifies a receptor for the Drosophila JAK/STAT signal transduction pathway
      and encodes a protein distantly related to the mammalian cytokine receptor
      family.
AB  - The JAK/STAT signal transduction pathway controls numerous events in Drosophila
      melanogaster development. Receptors for the pathway have yet to be identified.
      Here we have identified a Drosophila gene that shows embryonic mutant phenotypes
      identical to those in the hopscotch (hop)/JAK kinase and marelle (mrl)/Stat92e
      mutations. We named this gene master of marelle (mom). Genetic analyses place
      mom's function between upd (the ligand) and hop. We further show that cultured
      cells transfected with the mom gene bind UPD and activate the HOP/STAT92E signal
      transduction pathway. mom encodes a protein distantly related to the mammalian
      cytokine receptor family. These data show that mom functions as a receptor of the
      Drosophila JAK/STAT signal transduction pathway.

PMID- 11825881
TI  - Glycobiology of the synapse.
AB  - Synapses are the fundamental units of connectivity that link together the nervous
      system. Lectin studies from 30 years ago suggested that specific glycans are
      concentrated at neuromuscular synapses in the peripheral nervous system and at
      excitatory synapses in the brain. Subsequent studies have confirmed that
      particular glycan structures are localized at these synapses, including
      polysialic acid, high mannose, the cytotoxic T cell antigen, and forms of heparan
      sulfate. Though the role of these molecules in synapse formation and function is
      still poorly understood, there is increasing evidence that the function of agrin,
      a synaptogenic factor in neuromuscular formation, is modulated by several
      glycans. In addition, the recent generation of ST8SiaIV null mice strongly
      suggests a role for polysialic acid in synaptic plasticity in the some regions of
      the central nervous system.

PMID- 11825882
TI  - Microbial glycosaminoglycan glycosyltransferases.
AB  - Glycosaminoglycans, a class of linear polysaccharides composed of repeating
      disaccharide units containing a hexosamine, are important carbohydrates found in
      many organisms. Vertebrates utilize glycosaminoglycans in structural,
      recognition, adhesion, and signaling roles. Certain pathogenic bacteria produce
      extracellular capsules composed of glycosaminoglycans or glycosaminoglycan-like
      polymers that enhance the microbes' ability to infect or to colonize the host. In
      the period from 1993 to 2001, bacterial enzymes were discovered that catalyze the
      polymerization of the repeating unit of hyaluronan, chondroitin, or N
      acetylheparosan (unsulfated, unepimerized heparin). Depending on the specific
      carbohydrate and the microorganism, either a dual-action enzyme (synthase) that
      transfers two distinct monosaccharides or a pair of single-action transferases
      are utilized to synthesize the glycosaminoglycan polymer. Current views on the
      enzymology, structures, potential evolution, and the roles of the known
      glycosyltransferases from Streptococcus, Pasteurella, and Escherichia are
      discussed.

PMID- 11825883
TI  - The cytosolic and transmembrane domains of the beta 1,6 N
      acetylglucosaminyltransferase (C2GnT) function as a cis to medial/Golgi-targeting
      determinant.
AB  - The beta 1,6 N-acetylglucosaminyltransferase (C2GnT) has been recently mapped to
      the cis/medial-Golgi compartment. To analyze the Golgi-targeting determinants of
      C2GnT, we constructed various deletion mutants of the enzyme fused to the
      enhanced green fluorescent protein (EGFP) and localized these proteins by
      fluorescence microscopy in living cells. We found that the N-terminal peptide
      encompassing amino acids 1 to 32 represents the minimal Golgi-targeting signal
      sufficient to localize EGFP to the same compartment as the full-length C2GnT.
      This peptide makes up the cytoplasmic and the transmembrane domains of the enzyme
      and was referred to as CTd (cytoplasmic and transmembrane domains). We compared
      the Golgi-targeting efficiency of the C2GnT-derived CTd with its homologous
      domains from other glycosyltransferases, including the H-type alpha(1,2)
      fucosyltransferase (FucTI), the polypeptide N-acetylgalactosaminyltransferase-I
      (GalNAcT-I), the alpha(1,3)-fucosyltransferase VII (FucTVII), and the alpha(2,6)
      sialyltransferase (ST6Gal-I) and found that the Golgi-targeting determinants of
      these glycosyltransferases were also composed of their cytosolic and
      transmembrane domains. To investigate whether the CTd of C2GnT could serve as a
      cis to medial Golgi-specific signal, we tested its ability to mislocalize two
      late-Golgi acting glycosyltransferases FucTI and FucTVII. We show that fusing the
      C2GnT-derived CTd with the catalytic domain of FucTVII resulted in a complete
      mislocalization of the enzyme to the C2GnT compartment, with a parallel
      alteration of sialyl-Lewis x synthesis and P-selectin binding. The intracellular
      distribution and activity of FucTI, however, were not affected. Thus, CTds of
      either early or late-Golgi acting glycosyltransferases represent the Golgi
      targeting domains of these enzymes. In addition, we show that C2GnT-derived CTd
      can function as a cis/medial Golgi-targeting determinant.

PMID- 11825884
TI  - Trypanosoma cruzi surface mucin TcMuc-e2 expressed on higher eukaryotic cells
      induces human T cell anergy, which is reversible.
AB  - Chagas' disease is a chronic, debilitating, multisystemic disorder that affects
      millions of people in Latin America. The protozoan parasite Trypanosoma cruzi,
      the etiological agent of Chagas' disease, has a large number of O-glycosylated
      Thr/Ser/Pro-rich mucin molecules on its surface (TcMuc). These mucins are the
      main acceptors of sialic acid and have been suggested to play a role on various
      host-parasite interactions, such as adhesion to macrophages, protection from
      complement lysis, and immunomodulation of the immune response mounted by the
      host. To observe the immunologic effect obtained by the heterologous expression
      of a TcMuc gene in higher eukaryotic cells exposed to xenogeneic lymphocytes, we
      developed a strategy based on the transfection of a known T. cruzi mucin gene
      (TcMuc-e2) into Vero cells. In contrast to the brisk proliferation and activation
      of human lymphocytes observed at 3, 4, and 5 days induced by normal Vero cells,
      neither proliferation nor significant activation of human lymphocytes was
      observed with TcMuc-e2-transfected Vero cells. This TcMuc-e2 mucin-induced
      suppression of T cell response can be reversed by the addition of exogenous IL-2.
      In addition it was demonstrated that the immunosuppressive reaction was not
      related to the induction of an important degree of apoptosis in human
      lymphocytes. Posttranslational modification are required for the inhibitory
      effect that TcMuc-e2 exerts when transfected to Vero cells. O-glycosylation and
      sialylation are required to obtain the immunomodulatory effect as assessed by O
      sialoglycoprotease and neuraminidase treatments. These results are consistent
      with other studies showing that surface glycoconjugates from T. cruzi and
      mammalian cells can induce an inhibition of the immune response.

PMID- 11825885
TI  - Glycoprotein biosynthesis in porcine aortic endothelial cells and changes in the
      apoptotic cell population.
AB  - Porcine aortic endothelial cells (PAECs) produce glycoproteins with important
      biological functions, such as the control of cell adhesion, blood clotting, blood
      pressure, the immune system, and apoptosis. Cell surface glycoproteins play
      important roles in these biological activities. To understand the control of cell
      surface glycosylation, we elucidated biosynthetic pathways leading to N- and O
      glycans in PAECs. Based on the enzyme activities, PAECs should be rich in complex
      biantennary N-glycans. In addition, the enzymes synthesizing complex O-glycans
      with core 1 and 2 structures are present in PAECs. The first enzyme of the O
      glycosylation pathway, polypeptide GalNAc-transferase, was particularly active.
      Its specificity toward synthetic peptide substrates was found to be similar to
      that of purified bovine colostrum enzyme T1. A significant fraction of PAECs
      treated with tumour necrosis factor alpha or human serum detached from the
      culture plate, and most of these cells were apoptotic. The apoptotic cell
      population exhibited decreased core 2 beta 6-GlcNAc-transferase activity. In
      contrast, the activities of core 1 beta 3-Gal-transferase, which synthesizes O
      glycan core 1, and of alpha 3-sialyltransferase (O), which sialylates core 1,
      were increased in apoptotic PAECs. Thus, apoptotic PAECs are predicted to have
      fewer complex O-glycans and a higher proportion of short, sialylated core 1
      chains.

PMID- 11825886
TI  - Localization and characterization of polysialic acid-containing N-linked glycans
      from bovine NCAM.
AB  - The neural cell adhesion molecule (NCAM) plays important roles during
      development, plasticity, and regeneration in the adult nervous system. Its
      function is strongly influenced by attachment of the unusual alpha 2-8-linked
      polysialic acid (PSA). Here we analyzed the N-glycosylation pattern of
      polysialylated NCAM from brains of newborn calves. Purified PSA-NCAM glycoprotein
      was digested with trypsin, and PSA-glycopeptides were separated by immunoaffinity
      chromatography. For determining the N-glycosylation sites, PNGase F-treated
      glycopeptides were analyzed by Edman degradation and matrix-assisted laser
      desorption/ionization mass spectrometry (MALDI-MS). They were found to be
      exclusively linked to the fifth (Asn 439) and sixth (Asn 468) N-glycosylation
      sites in the fifth immunoglobulin-like domain of NCAM. The chain length of PSA
      consisted of at least 30 sialic acid residues, as shown by anion exchange
      chromatography. For analysis of the core structures, endoneuraminidase N-treated
      PSA-NCAM was separated by SDS-PAGE and digested with PNGase F. The core
      structures of polysialylated glycans were characterized by MALDI-MS combined with
      exoglycosidase digestions and chromatographic fractionation. They include hybrid,
      di-, tri-, and small amounts of tetraantennary carbohydrates, which were all
      fucosylated at the innermost N-acetylglucosamine. For the triantennary glycans,
      the "2,6" arm was preferred in polysialylated structures. High levels of sulfated
      groups were found on polysialylated structures and to a lower extent also on
      nonpolysialylated glycans. In addition, high-mannose-type glycans could be
      detected on PSA-NCAM glycoforms ranging from (GlcNAc)(2)(Man)(5) up to
      (GlcNAc)(2)(Man)(9). In conclusion, we observed a structural variability and high
      regional selectivity for the PSA-glycans attached to the NCAM molecule that are
      most likely influencing its biological functions.

PMID- 11825888
TI  - Antiapoptotic activity of the free caspase recruitment domain of procaspase-9: a
      novel endogenous rescue pathway in cell death.
AB  - Mitochondrial injury initiates proteolytic processing of procaspase-9 into the
      large and small subunits, leading to apoptotic cell death. Here we show that the
      free caspase recruitment domain (CARD) released by procaspase-9 processing
      activates nuclear factor kappaB expression. A procaspase-9 construct with a point
      mutation that abrogates the release of the CARD abolished nuclear factor kappaB
      activation. Most importantly, the free CARD is shown to enhance the expression of
      the gene encoding the antiapoptotic Bcl-x protein and to strongly inhibit
      apoptosis. This is the first demonstration that different domains of the same
      caspase protein have proapoptotic and antiapoptotic effects and suggests that the
      relative effects of these domains are important in regulating the balance between
      death and survival.

PMID- 11825889
TI  - Vinexin beta regulates the anchorage dependence of ERK2 activation stimulated by
      epidermal growth factor.
AB  - ERK is activated by soluble growth factors in adherent cells. However, activation
      of ERK is barely detectable and not sufficient for cell proliferation in non
      adherent cells. Here, we show that exogenous expression of vinexin beta, a novel
      focal adhesion protein, allows anchorage-independent ERK2 activation stimulated
      by epidermal growth factor. In contrast, expression of vinexin beta had no effect
      on ERK2 activation in adherent cells, suggesting that vinexin beta regulates the
      anchorage dependence of ERK2 activation. Analyses using deletion mutants
      demonstrated that a linker region between the second and third SH3 domains of
      vinexin beta, but not the SH3 domains, is required for this function of vinexin
      beta. To evaluate the pathway regulating the anchorage dependence of ERK2
      activation, we used a dominant-negative mutant of p21-activated kinase (PAK) and
      a specific inhibitor (H89) of cAMP-dependent protein kinase (PKA) because PAK and
      PKA are known to regulate the anchorage dependence of ERK2 activation. The
      dominant-negative mutant of PAK suppressed the anchorage-independent ERK2
      activation induced by expression of vinexin beta. The dominant-negative mutant of
      vinexin beta inhibited the anchorage-independent ERK2 activation induced by the
      PKA inhibitor. Together, these observations indicate that vinexin beta plays a
      key role in regulating the anchorage dependence of ERK2 activation through PKA
      PAK signaling.

PMID- 11825890
TI  - The inhibition of glutamate release by metabotropic glutamate receptor 7 affects
      both [Ca2+]c and cAMP: evidence for a strong reduction of Ca2+ entry in single
      nerve terminals.
AB  - Metabotropic glutamate receptors (mGluRs) from group III reduce glutamate
      release. Because these receptors reduce cAMP levels, we explored whether this
      signaling pathway contributes to release inhibition caused by mGluRs with low
      affinity for L-2-amino-4-phosphonobutyrate (L-AP4). In biochemical experiments
      with the population of cerebrocortical nerve terminals we find that L-AP4 (1 mm)
      inhibited the Ca(2+)-dependent-evoked release of glutamate by 25%. This
      inhibitory effect was largely prevented by the pertussis toxin but was
      insensitive to inhibitors of protein kinase C bisindolylmaleimide and protein
      kinase A H-89. Furthermore, this inhibition was associated with reduction in N
      type Ca(2+) channel activity in the absence of any detectable change in cAMP
      levels. In the presence of forskolin, however, L-AP4 decreased the levels of
      cAMP. The activation of this additional signaling pathway was very efficient in
      counteracting the facilitation of glutamate release induced either by forskolin
      or the beta-adrenergic receptor agonist isoproterenol. Imaging experiments to
      measure Ca(2+) dynamics in single nerve terminals showed that L-AP4 strongly
      reduced the Ca(2+) response in 28% of the nerve terminals. Moreover,
      immunochemical experiments showed that 25-35% of the nerve terminals that were
      immunopositive to synaptophysin were also immunoreactive to the low affinity L
      AP4-sensitive mGluR7. Then, mGluR7 mediates the inhibition of glutamate release
      caused by 1 mm L-AP4, primarily by a strong inhibition of Ca(2+) channels,
      although high cAMP uncovers the receptor ability to decrease cAMP.

PMID- 11825891
TI  - Alternative splicing of the adenylyl cyclase stimulatory G-protein G alpha(s) is
      regulated by SF2/ASF and heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) and
      involves the use of an unusual TG 3'-splice Site.
AB  - The factors involved in regulating alternative splicing of the human adenylyl
      cyclase stimulatory G-protein G alpha(s) in different cell types remain
      undefined. We have designed a G alpha(s) minigene that retains the signals
      required for G alpha(s) alternative splicing in vivo. Employing transient
      transfection of human myometrial smooth muscle cells and HeLa cells, as well as
      in vitro splicing assays, we have provided evidence that the antagonistic
      splicing factors SF2/ASF and hnRNPA1 act as potent regulators of G alpha(s)
      isoform expression in these cells. Both SF2/ASF and hnRNPA1 control the selection
      of competing 5'-splice sites and respectively promote inclusion or skipping of
      the small cassette-type exon 3 of G alpha(s) transcripts, resulting in the
      generation of G alpha(s)-long and G alpha(s)-short mRNA isoforms. We have also
      provided evidence that SF2/ASF and hnRNPA1 play a role in 3'-splice site
      selection involving the use of a non-canonical TG 3'-splice site preceding exon
      4. Using a score-matrix analysis to identify putative exonic enhancer sequences
      (ESEs), we found multiple high score ESE motifs for SF2/ASF, SC35, and SRp40 in
      exon 3 of G alpha(s). These results suggest that tissue-specific expression of
      SF2/ASF and hnRNPA1 governs the expression of alternative isoforms of G alpha(s)
      in these different cells types.

PMID- 11825892
TI  - Tandem function of nucleotide binding domains confers competence to sulfonylurea
      receptor in gating ATP-sensitive K+ channels.
AB  - Fundamental to the metabolic sensor function of ATP-sensitive K(+) (K(ATP))
      channels is the sulfonylurea receptor. This ATP-binding cassette protein, which
      contains nucleotide binding domains (NBD1 and NBD2) with conserved Walker motifs,
      regulates the ATP sensitivity of the pore-forming Kir6.2 subunit. Although NBD2
      hydrolyzes ATP, a property essential in K(ATP) channel gating, the role of NBD1,
      which has limited catalytic activity, if at all, remains less understood. Here,
      we provide functional evidence that cooperative interaction, rather than the
      independent contribution of each NBD, is critical for K(ATP) channel regulation.
      Gating of cardiac K(ATP) channels by distinct conformations in the NBD2 ATPase
      cycle, induced by gamma-phosphate analogs, was disrupted by point mutation not
      only of the Walker motif in NBD2 but also in NBD1. Cooling membrane patches to
      decelerate the intrinsic ATPase activity counteracted ATP-induced K(ATP) channel
      inhibition, an effect that mimicked stabilization of the MgADP-bound
      posthydrolytic state at NBD2 by the gamma-phosphate analog orthovanadate.
      Temperature-induced channel activation was abolished by mutations that either
      prevent stabilization of MgADP at NBD2 or ATP at NBD1. These findings provide a
      paradigm of K(ATP) channel gating based on integration of both NBDs into a
      functional unit within the multimeric channel complex.

PMID- 11825893
TI  - Repair of nitric oxide-modified ferredoxin [2Fe-2S] cluster by cysteine
      desulfurase (IscS).
AB  - Iron-sulfur proteins are among the sensitive targets of the nitric oxide
      cytotoxicity. When Escherichia coli cells are exposed to nitric oxide, iron
      sulfur clusters are modified forming protein-bound dinitrosyl iron complexes.
      Such modified protein dinitrosyl iron complexes are stable in vitro but are
      efficiently repaired in aerobically growing E. coli cells even without any new
      protein synthesis. Here we show that cysteine desulfurase encoded by the gene
      iscS of E. coli can directly convert the ferredoxin dinitrosyl iron complex to
      the ferredoxin [2Fe-2S] cluster in the presence of L-cysteine in vitro. A
      reassembly of the [2Fe-2S] cluster in the ferredoxin dinitrosyl iron complex does
      not require any addition of iron or other protein components. Furthermore, a
      complete removal of the dinitrosyl iron complex from ferredoxin prevents
      reassembly of the [2Fe-2S] cluster in the protein. The results suggest that
      cysteine desulfurase (IscS) together with L-cysteine can efficiently repair the
      nitric oxide-modified ferredoxin [2Fe-2S] cluster and that the iron center in the
      dinitrosyl iron complex may be recycled for the reassembly of iron-sulfur
      clusters in proteins.

PMID- 11825894
TI  - Myristoylated alanine-rich C kinase substrate (MARCKS) sequesters spin-labeled
      phosphatidylinositol 4,5-bisphosphate in lipid bilayers.
AB  - The myristoylated alanine-rich protein kinase C substrate (MARCKS) may function
      to sequester phosphoinositides within the plane of the bilayer. To characterize
      this interaction with phosphatidylinositol 4,5-bisphosphate (PI(4,5)P(2)), a
      novel spin-labeled derivative, proxyl-PIP(2), was synthesized and characterized.
      In the presence of molecules known to bind PI(4,5)P(2) the EPR spectrum of this
      label exhibits an increase in line width because of a decrease in label dynamics,
      and titration of this probe with neomycin yields the expected 1:1 stoichiometry.
      Thus, this probe can be used to quantitate the interactions made by the
      PI(4,5)P(2) head group within the bilayer. In the presence of a peptide
      comprising the effector domain of MARCKS the EPR spectrum broadens, but the
      changes in line shape are modulated by both changes in label correlation time and
      spin-spin interactions. This result indicates that at least some proxyl-PIP(2)
      are in close proximity when bound to MARCKS and that MARCKS associates with
      multiple PI(4,5)P(2) molecules. Titration of the proxyl-PIP(2) EPR signal by the
      MARCKS-derived peptide also suggests that multiple PI(4,5)P(2) molecules interact
      with MARCKS. Site-directed spin labeling of this peptide shows that the position
      and conformation of this protein segment at the membrane interface are not
      altered significantly by binding to PI(4,5)P(2). These data are consistent with
      the hypothesis that MARCKS functions to sequester multiple PI(4,5)P(2) molecules
      within the plane of the membrane as a result of interactions that are driven by
      electrostatic forces.

PMID- 11825895
TI  - The catabolic fate of nitric oxide: the nitric oxide oxidase and peroxynitrite
      reductase activities of cytochrome oxidase.
AB  - Stimulation of cardiomyocytes to endogenously evolve nitric oxide is shown by
      microsensor measurements on single cells to lead to transient nitric oxide
      concentrations of a few hundred nanomolar. At these submicromolar concentrations,
      no evidence could be found for the expected reaction between nitric oxide
      generated and the oxymyoglobin present in the cells: nitric oxide + oxymyoglobin 
      -> nitrate + metmyoglobin. No metmyoglobin formation was detected by electron
      paramagnetic resonance spectroscopy, and microsensor measurements revealed near
      quantitative conversion of the nitric oxide to nitrite rather than nitrate ion.
      Moreover, the rate of nitrite formation is shown to be too rapid to be accounted
      for by non-enzymatic means. The essentially quantitative and rapid catabolism of
      nitric oxide to nitrite ion can plausibly be explained on the basis of a cycle of
      reactions catalyzed by cytochrome c oxidase. It is demonstrated with the purified
      hemoproteins in vitro that the terminal oxidase can outcompete oxymyoglobin for
      available nitric oxide. It is proposed that under normal physiological and most
      pathological (non-inflammatory) conditions, reaction with cytochrome c oxidase is
      the major route by which NO is removed from mitochondria-rich cells.

PMID- 11825887
TI  - Elucidation of the metabolic fate of glucose in the filamentous fungus
      Trichoderma reesei using expressed sequence tag (EST) analysis and cDNA
      microarrays.
AB  - Despite the intense interest in the metabolic regulation and evolution of the ATP
      producing pathways, the long standing question of why most multicellular
      microorganisms metabolize glucose by respiration rather than fermentation remains
      unanswered. One such microorganism is the cellulolytic fungus Trichoderma reesei
      (Hypocrea jecorina). Using EST analysis and cDNA microarrays, we find that in T.
      reesei expression of the genes encoding the enzymes of the tricarboxylic acid
      cycle and the proteins of the electron transport chain is programmed in a way
      that favors the oxidation of pyruvate via the tricarboxylic acid cycle rather
      than its reduction to ethanol by fermentation. Moreover, the results indicate
      that acetaldehyde may be channeled into acetate rather than ethanol, thus
      preventing the regeneration of NAD(+), a pivotal product required for anaerobic
      metabolism. The studies also point out that the regulatory machinery controlled
      by glucose was most probably the target of evolutionary pressure that directed
      the flow of metabolites into respiratory metabolism rather than fermentation.
      This finding has significant implications for the development of metabolically
      engineered cellulolytic microorganisms for fuel production from cellulose
      biomass.

PMID- 11825896
TI  - Selection and identification of dense granule antigen GRA3 by Toxoplasma gondii
      whole genome phage display.
AB  - Toxoplasma gondii is a ubiquitous, unicellular, eukaryotic parasite with a
      complex intracellular life cycle capable of invading and chronically infecting a
      wide variety of vertebrate host species, including man. Although normally
      opportunistic in healthy adults, it is a lethal pathogen in immunocompromised
      humans, particularly in AIDS patients. We present the application of a genomic
      phage display as a tool for the direct identification of antigens with potential
      value in diagnosis and/or as subunit vaccine components. Using a polycosmid
      cloning strategy, we constructed a large phagemid display library (>10(9)
      independent clones) of mixed short genomic restriction fragments (< or = 500 bp)
      of T. gondii genomic DNA (80 Mbp genome size) fused to gene III of the
      filamentous phage M13. Biopanning of the library with monoclonal Toxoplasma
      antibodies resulted in the isolation and identification of an epitope of GRA3, an
      antigen located in the dense granules of T. gondii tachyzoites. The reactivity of
      the phage displaying the GRA3 epitope with the monoclonal antibody was confirmed
      by an enzyme-linked immunosorbent assay. These results demonstrate the
      accessibility of midsized eukaryotic genomes to display technology and the
      feasibility to screen these whole genome display libraries with antibodies for
      isolating novel antigenic determinants.

PMID- 11825897
TI  - Cleavage specificity of Saccharomyces cerevisiae flap endonuclease 1 suggests a
      double-flap structure as the cellular substrate.
AB  - Flap endonuclease 1 (FEN1) is a structure-specific nuclease that cleaves
      substrates containing unannealed 5'-flaps during Okazaki fragment processing.
      Cleavage removes the flap at or near the point of annealing. The preferred
      substrate for archaeal FEN1 or the 5'-nuclease domains of bacterial DNA
      polymerases is a double-flap structure containing a 3'-tail on the upstream
      primer adjacent to the 5'-flap. We report that FEN1 in Saccharomyces cerevisiae
      (Rad27p) exhibits a similar specificity. Cleavage was most efficient when the
      upstream primer contained a 1-nucleotide 3'-tail as compared with the fully
      annealed upstream primer traditionally tested. The site of cleavage was
      exclusively at a position one nucleotide into the annealed region, allowing human
      DNA ligase I to seal all resulting nicks. In contrast, a portion of the products
      from traditional flap substrates is not ligated. The 3'-OH of the upstream primer
      is not critical for double-flap recognition, because Rad27p is tolerant of
      modifications. However, the positioning of the 3'-nucleotide defines the site of
      cleavage. We have tested substrates having complementary tails that equilibrate
      to many structures by branch migration. FEN1 only cleaved those containing a 1
      nucleotide 3'-tail. Equilibrating substrates containing 12-ribonucleotides at the
      end of the 5'-flap simulates the situation in vivo. Rad27p cleaves this substrate
      in the expected 1-nucleotide 3'-tail configuration. Overall, these results
      suggest that the double-flap substrate is formed and cleaved during eukaryotic
      DNA replication in vivo.

PMID- 11825898
TI  - Three SIBLINGs (small integrin-binding ligand, N-linked glycoproteins) enhance
      factor H's cofactor activity enabling MCP-like cellular evasion of complement
      mediated attack.
AB  - Previously we have shown that two members of the newly named SIBLING (small
      integrin-binding ligand, N-linked glycoproteins) family of proteins, bone
      sialoprotein, and osteopontin, bound first to a cell surface receptor and then to
      complement Factor H thereby blocking the lytic activity of the alternative
      pathway of complement. Another member of this family, dentin matrix protein 1, is
      shown in this paper to be very similar to osteopontin in that it can bind
      strongly to Factor H (K(a) approximately 1 nm) and block the lytic activity
      through either the vitronectin receptor (alpha(V)beta(3) integrin) or CD44.
      Binding of Factor H to SIBLING localized to the cells surface was demonstrated by
      fluorescence-activated cell sorting. Extensive overlapping fragment analyses
      suggests that both dentin matrix protein 1 and osteopontin interact with cell
      surface CD44 through their amino termini. Similar fragments of bone sialoprotein,
      like the intact protein, did not functionally interact with CD44. All three
      proteins are shown to act in conjunction with Factor I, a serum protease that,
      when complexed to appropriate cofactors, stops the lytic pathway by digesting the
      bound C3b in a series of proteolytic steps. These results show that at least
      three members of this family confer membrane cofactor protein-like activity (MCP
      or CD46) upon cells expressing RGD-binding integrins or CD44. The required order
      of the assembly of the complex suggests that this cofactor activity is limited to
      short diffusional distances.

PMID- 11825899
TI  - Protein kinase C-dependent, CCAAT/enhancer-binding protein beta-mediated
      expression of insulin-like growth factor I gene.
AB  - The possible involvement of the protein kinase C (PKC) pathway in transcriptional
      regulation of the human insulin-like growth factor-I (IGF-I) gene has been
      suggested. In this study, we sought to determine whether a PKC-dependent pathway
      is implicated in the transcriptional control, and if it is, how this occurs.
      Treatment with 12-O-tetradecanoylphorbol 13-acetate (TPA) caused an increase in
      the activity of the human IGF-I gene major promoter in HepG2 cells. A
      CCAAT/enhancer-binding protein (C/EBP) binding site located at +22 to +30 was
      bound by C/EBP beta in a TPA-dependent manner and was solely responsible for the
      TPA responsiveness. This increase in C/EBP beta activity occurs through
      transcriptional and posttranslational regulation, and the latter is mediated by
      activation of p90 ribosomal S6 kinase (RSK): co-expression of dominant negative
      RSK abolished the TPA-responsive and C/EBP beta-dependent transactivation. Also,
      TPA-responsive activation of GAL4-C/EBP beta chimera required the Ser residue
      known as the RSK target. In SK-N-MC cells, which display constitutive, high
      expression of IGF-I on use of the major promoter, a large amount of C/EBP beta
      binding was observed with the C/EBP site in the basal state. Treatment with PKC
      inhibitors substantially reduced the promoter activity and mRNA amounts of IGF-I,
      with the binding of C/EBP beta to the C/EBP site also being reduced. When the
      C/EBP site was disrupted, the basal promoter activity was reduced, but the
      reduction by the PKC inhibitor was no longer observed. These observations suggest
      that the increase of C/EBP beta binding to the C/EBP site, which is in part
      mediated via activation of RSK, can primarily explain the TPA responsiveness of
      the IGF-I gene promoter. The intrinsic PKC activity in SK-N-MC cells should play
      a major role in the constitutive, high expression of IGF-I and may therefore
      contribute in part to the maintenance of the tumor phenotype of the cells.

PMID- 11825900
TI  - Genetic analysis of the mammalian K+ channel beta subunit Kvbeta 2 (Kcnab2).
AB  - Kvbeta2 binds to K(+) channel alpha subunits from at least two different families
      (Kv1 and Kv4) and is a member of the aldo-ketoreductase (AKR) superfamily.
      Proposed functions for this protein in vivo include a chaperone-like role in Kv1
      alpha subunit biogenesis and catalytic activity as an AKR oxidoreductase. To
      investigate the in vivo function of Kvbeta2, Kvbeta2-null and point mutant (Y90F)
      mice were generated through gene targeting in embryonic stem cells. In Kvbeta2
      null mice, Kv1.1 and Kv1.2 localize normally in cerebellar basket cell terminals
      and the juxtaparanodal region of myelinated nerves. Moreover, normal
      glycosylation patterns are observed for Kv1.1 and Kv1.2 in whole brain lysates.
      Thus, loss of the chaperone-like activity does not appear to account for the
      phenotype of Kvbeta2-null mice, which include reduced life spans, occasional
      seizures, and cold swim-induced tremors similar to that observed in Kv1.1-null
      mice. Mice expressing Kvbeta2, mutated at a site (Y90F) that abolishes AKR-like
      catalytic activity in other family members, have no overt phenotype. We conclude
      that Kvbeta2 contributes to regulation of excitability in vivo, although not
      directly through either chaperone-like or typical AKR catalytic activity. Rather,
      Kvbeta2 relies upon as yet unidentified mechanisms in the regulation of K(+)
      channel and/or oxidoreductive functions.

PMID- 11825901
TI  - Ribosome-inactivating and adenine polynucleotide glycosylase activities in
      Mirabilis jalapa L. tissues.
AB  - Several tissues of Mirabilis jalapa L. (Nyctaginaceae) were assayed for
      inhibition of translation by a rabbit reticulocyte lysate (as a signal of
      ribosome-inactivating activity) and for adenine DNA glycosylase activity,
      activities that are both due to the presence of a class of enzymes called
      ribosome-inactivating proteins (RIPs), currently classified as rRNA N
      glycosylases (EC ). These activities were highest in seed; intermediate in flower
      bud, immature seed, sepal + gynoecium, leaf, and root; and very low in all other
      tissues. By cation-exchange chromatography, four protein peaks with inhibitory
      activity on cell-free translation were identified in extracts from seeds, and two
      proteins were isolated from peaks 1 and 4, all of which have the properties of
      single-chain type 1 RIP. One is Mirabilis antiviral protein (MAP), so far
      purified only from roots. The second is a new protein that we propose to call MAP
      4. The distribution of MAP and MAP-4 in several tissues was determined with a
      novel experimental approach based on liquid chromatography/mass spectrometry. The
      direct enzymatic activity of MAP on several substrates is described here for the
      first time. MAP depurinated not only rRNA in intact ribosomes, thus inhibiting
      protein synthesis, but also other polynucleotides such as poly(A), DNA, and
      tobacco mosaic virus RNA. Autologous DNA was depurinated more extensively than
      other polynucleotides. Therefore, the enzymatic activity of this protein may be
      better described as adenine polynucleotide glycosylase activity rather than rRNA
      N-glycosylase activity. Finally, MAP does not cross-react immunologically with
      other commonly utilized RIPs.

PMID- 11825902
TI  - Linkage of caspase-mediated degradation of paxillin to apoptosis in Ba/F3 murine
      pro-B lymphocytes.
AB  - We have cloned the complete cDNA from mouse paxillin, a 68-kDa adapter protein
      found in focal adhesions. We found that paxillin was degraded by caspases in
      Ba/F3 cell apoptosis induced by withdrawal of interleukin-3 (IL-3), a survival
      factor for this cell, and by ionizing radiation. Also, paxillin was degraded in
      vitro by incubation with recombinant caspase-3. Western blot analyses of
      degradation products of overexpressed green fluorescence protein-tagged paxillin
      and site-specific mutants demonstrated that Asp-102 and Asp-301 were early
      caspase cleavage sites, and Asp-5, Asp-146, Asp-165, and Asp-222 were late
      cleavage sites. Overexpression of paxillin delayed apoptosis of Ba/F3 after IL-3
      withdrawal. Furthermore, this anti-apoptotic effect of paxillin was augmented by
      a triple mutation in aspartic acids at caspase cleavage sites. These results
      suggest that paxillin plays a critical role in cell survival signaling and that
      the cleavage of paxillin by caspases might be an important event for focal
      adhesion disassembly during cell apoptosis, contributing to detachment, rounding,
      and death.

PMID- 11825903
TI  - Quantitative assessment of gene targeting in vitro and in vivo by the pancreatic
      transcription factor, Pdx1. Importance of chromatin structure in directing
      promoter binding.
AB  - The transcription factor Pdx1 is expressed in the pancreatic beta-cell, where it
      is believed to regulate several beta-cell-specific genes. Whereas binding by Pdx1
      to elements of beta-cell genes has been demonstrated in vitro, almost none of
      these genes has been demonstrated to be a direct binding target for Pdx1 within
      cells (where complex chromatin structure exists). To determine which beta-cell
      promoters are bound by Pdx1 in vivo, we performed chromatin immunoprecipitation
      assays using Pdx1 antiserum and chromatin from beta-TC3 cells and Pdx1
      transfected NIH3T3 cells and subsequently quantitated co-immunoprecipitated
      promoters using real-time PCR. We compared these in vivo findings to parallel
      immunoprecipitations in which Pdx1 was allowed to bind to promoter fragments in
      in vitro reactions. Our results show that in all cells Pdx1 binds strongly to the
      insulin, islet amyloid polypeptide, glucagon, Pdx1, and Pax4 promoters, whereas
      it does not bind to either the glucose transporter type 2 or albumin promoters.
      In addition, no binding by Pdx1 to the glucokinase promoter was observed in beta
      cells. In contrast, in in vitro immunoprecipitations, Pdx1 bound all promoters to
      an extent approximately proportional to the number of Pdx1 binding sites. Our
      findings suggest a critical role for chromatin structure in directing the
      promoter binding selectivity of Pdx1 in beta-cells and non-beta-cells.

PMID- 11825904
TI  - The role of the cross-link His-Tyr in the functional properties of the binuclear
      center in cytochrome c oxidase.
AB  - Resonance Raman and Fourier transform infrared spectroscopies have been used to
      study the aa(3)-type cytochrome c oxidase and the Y280H mutant from Paracoccus
      denitrificans. The stability of the binuclear center in the absence of the
      Tyr(280)-His(276) cross-link is not compromised since heme a(3) retains the same
      proximal environment, spin, and coordination state as in the wild type enzyme in
      both the oxidized and reduced states. We observe two C-O modes in the Y280H
      mutant at 1966 and 1975 cm(-1). The 1975 cm(-1) mode is assigned to a gamma-form
      and represents a structure of the active site in which Cu(B) exerts a steric
      effect on the heme a(3)-bound CO. Therefore, the role of the cross-link is to fix
      Cu(B) in a certain configuration and distance from heme a(3), and not to allow
      histidine ligands to coordinate to Cu(B) rather than to heme a(3), rendering the
      enzyme inactive, as proposed recently (Das, T. K., Pecoraro, C., Tomson, F. L.,
      Gennis, R. B., and Rousseau, D. L. (1998) Biochemistry 37, 14471-14476). The
      results provide solid evidence that in the Y280H mutant the catalytic site
      retains its active configuration that allows O(2) binding to heme a(3).
      Oxygenated intermediates are formed by mixing oxygen with the CO-bound mixed
      valence wild type and Y280H enzymes with similar Soret maxima at 438 nm.

PMID- 11825905
TI  - Assembly limits the pharmacological complexity of ATP-sensitive potassium
      channels.
AB  - ATP-sensitive potassium channels (K(ATP) channels) are formed from an octameric
      complex of an inwardly rectifying K(+) channel (Kir6.1, Kir6.2) and a
      sulfonylurea receptor (SUR1, SUR2A, and SUR2B). In this study we have attempted
      to address the question of whether SUR heteromultimers can form using a
      combination of biochemical and electrophysiological approaches. We have
      constructed monoclonal stable lines in HEK293 cells co-expressing Kir6.2 with
      SUR1 and SUR2A. Using coimmunoprecipitation analysis with SUR isotype-specific
      antibodies two biochemical populations are distinguished, one containing SUR1 and
      the other SUR2A. It is not possible to detect immune complexes containing both
      SUR1 and SUR2A. Functional studies were undertaken and whole cell membrane
      currents were studied using the patch clamp. Concentrations of sulfonylureas and
      potassium channel openers were determined that selectively inhibited or activated
      SUR1/Kir6.2 and SUR2A/Kir6.2. In the cell line expressing SUR1/SUR2AKir6.2 we
      were unable to demonstrate a population of channels with unique pharmacological
      properties. Thus we conclude from these studies that heteromultimeric channel
      complexes containing both SUR1 and SUR2A are not formed, suggesting an
      incompatibility between different SUR subtypes. This incompatibility limits the
      pharmacological complexity of K(ATP) channels that may be observed in native
      tissues.

PMID- 11825906
TI  - The solution structure of acyl carrier protein from Mycobacterium tuberculosis.
AB  - Acyl carrier protein (ACP) performs the essential function of shuttling the
      intermediates between the enzymes that constitute the type II fatty acid synthase
      system. Mycobacterium tuberculosis is unique in producing extremely long mycolic
      acids, and tubercular ACP, AcpM, is also unique in possessing a longer carboxyl
      terminus than other ACPs. We determined the solution structure of AcpM using
      protein NMR spectroscopy to define the similarities and differences between AcpM
      and the typical structures. The amino-terminal region of the structure is well
      defined and consists of four helices arranged in a right-handed bundle held
      together by interhelical hydrophobic interactions similar to the structures of
      other bacterial ACPs. The unique carboxyl-terminal extension from helix IV has a
      "melted down" feature, and the end of the molecule is a random coil. A comparison
      of the apo- and holo-forms of AcpM revealed that the 4'-phosphopantetheine group
      oscillates between two states; in one it is bound to a hydrophobic groove on the
      surface of AcpM, and in another it is solvent-exposed. The similarity between
      AcpM and other ACPs reveals the conserved structural motif that is recognized by
      all type II enzymes. However, the function of the coil domain extending from
      helix IV to the carboxyl terminus remains enigmatic, but its structural
      characteristics suggest that it may interact with the very long chain
      intermediates in mycolic acid biosynthesis or control specific protein-protein
      interactions.

PMID- 11825907
TI  - Allosteric communication between signal peptides and the SecA protein DEAD motor
      ATPase domain.
AB  - SecA, the preprotein translocase ATPase is built of an amino-terminal DEAD
      helicase motor domain bound to a regulatory C-domain. SecA recognizes mature and
      signal peptide preprotein regions. We now demonstrate that the amino-terminal 263
      residues of the ATPase subdomain of the DEAD motor are necessary and sufficient
      for high affinity signal peptide binding. Binding is abrogated by deletion of
      residues 219-244 that lie within SSD, a novel substrate specificity element of
      the ATPase subdomain. SSD is essential for protein translocation, is unique to
      SecA, and is absent from other DEAD proteins. Signal peptide binding to the DEAD
      motor is controlled in trans by the C-terminal intramolecular regulator of ATPase
      (IRA1) switch. IRA1 mutations that activate the DEAD motor ATPase also enhance
      signal peptide affinity. This mechanism coordinates signal peptide binding with
      ATPase activation. Signal peptide binding causes widespread conformational
      changes to the ATPase subdomain and inhibits the DEAD motor ATPase. This involves
      an allosteric mechanism, since binding occurs at sites that are distinct from the
      catalytic ATPase determinants. Our data reveal the physical determinants and
      sophisticated intramolecular regulation that allow signal peptides to act as
      allosteric effectors of the SecA motor.

PMID- 11825908
TI  - Phosphatidylinositol 3-kinase and Src family kinases are required for
      phosphorylation and membrane recruitment of Dok-1 in c-Kit signaling.
AB  - Dok-1 is an adaptor protein that is a substrate for Bcr-Abl and other tyrosine
      protein kinases. The presence of pleckstrin homology and phosphotyrosine binding
      domains as well as multiple tyrosine phosphorylation sites suggests that Dok-1 is
      involved in protein-protein and/or protein-lipid interactions. Here we show that
      stimulation of Mo7 hematopoietic cells with c-Kit ligand (KL) induces
      phosphatidylinositol (PI) 3-kinase-dependent tyrosine phosphorylation and
      membrane recruitment of Dok-1. Addition of the K-Ras membrane-targeting motif to
      Dok-1 generated a constitutively membrane-bound Dok-1 protein whose tyrosine
      phosphorylation was independent of PI 3-kinase. Membrane localization of Dok-1
      was required for its ability to function as a negative regulator of cell
      proliferation. Additional experiments revealed that Dok-1 associated with the
      juxtamembrane region and C-terminal tail of c-Kit. Lyn promoted phosphorylation
      of c-Kit and association of c-Kit and Dok-1. Both Lyn and Tec were capable of
      phosphorylating Dok-1. However, the use of primary bone marrow mast cells from
      normal and Lyn-deficient mice demonstrated that Lyn is required for KL-dependent
      Dok-1 tyrosine phosphorylation. Taken together, these data indicate that
      activation of PI 3-kinase by KL promotes binding of the Dok pleckstrin homology
      domain and Dok-1 recruitment to the plasma membrane where Dok-1 is phosphorylated
      by Src and/or Tec family kinases.

PMID- 11825909
TI  - Cellubrevin alterations and Mycobacterium tuberculosis phagosome maturation
      arrest.
AB  - The intracellular trafficking processes controlling phagosomal maturation remain
      to be fully delineated. Mycobacterium tuberculosis var. bovis BCG, an organism
      that causes phagosomal maturation arrest, has emerged as a tool for dissection of
      critical phagosome biogenesis events. In this work, we report that cellubrevin, a
      v-SNARE functioning in endosomal recycling and implicated in endosomal
      interactions with post-Golgi compartments, plays a role in phagosomal maturation
      and that it is altered on mycobacterial phagosomes. Both mycobacterial
      phagosomes, which undergo maturation arrest, and model phagosomes containing
      latex beads, which follow the normal pathway of maturation into phagolysosomes,
      acquired cellubrevin. However, the mycobacterial and model phagosomes differed,
      as a discrete proteolytic degradation of this SNARE was detected on mycobacterial
      phagosomes. The observed cellubrevin alteration on mycobacterial phagosomes was
      not a passive event secondary to a maturation arrest at another checkpoint of the
      phagosome maturation pathway, since pharmacological inhibitors of
      phagosomal/endosomal pathways blocking phagosomal maturation did not cause
      cellubrevin degradation on model phagosomes. Cellubrevin status on phagosomes had
      consequences on phagosomal membrane and lumenal content trafficking, involving
      plasma membrane marker recycling and delivery of lysosomal enzymes. These results
      suggest that cellubrevin plays a role in phagosomal maturation and that it is a
      target for modification by mycobacteria or by infection-induced processes in the
      host cell.

PMID- 11825910
TI  - Human Apg3p/Aut1p homologue is an authentic E2 enzyme for multiple substrates,
      GATE-16, GABARAP, and MAP-LC3, and facilitates the conjugation of hApg12p to
      hApg5p.
AB  - Autophagy is a process of bulk degradation of cytoplasmic components by the
      lysosome/vacuole and has a significant relationship to several neurodegenerative
      disorders and myopathies in mammals. One of APG gene products essential for
      autophagy in yeast, Apg3p, is a protein-conjugating enzyme for Apg8p lipidation
      (Ichimura, Y., Kirisako, T., Takao, T., Satomi, Y., Shimonishi, Y., Ishihara, N.,
      Mizushima, N., Tanida, I., Kominami, E., Ohsumi, M., Noda, T., and Ohsumi, Y.
      (2000) Nature 408, 488-492). In this study, the cloning of a human Apg3p
      homologue (hApg3p) as an E2 enzyme essential for human Apg8p homologues (i.e.
      GATE-16, GABARAP, and MAP-LC3) is shown, and its unique characteristics are
      described. The predicted amino acid sequence of the isolated clone shows 34.1%
      identity and 48.1% similarity to yeast Apg3p. Site-directed mutagenesis revealed
      that Cys(264) of hApg3p is an authentic active-site cysteine residue essential
      for the formation of hApg3p small middle dothApg8p homologue intermediates.
      Overexpression of hApg7p enhances the formation of a stable E2-substrate complex
      between hApg3p(C264S) and each of the hApg8p homologues, and MAP-LC3 is preferred
      as the substrate over the other two Apg8p homologues. These results indicate that
      hApg3p is an E2-like enzyme essential for three human Apg8p homologues. Co
      immunoprecipitation of hApg7p with hApg3p indicates that hApg3p forms an E1.E2
      complex with hApg7p as in the case of yeast Apg3p and Apg7p. Furthermore, hApg3p
      coimmunoprecipitates with hApg12p, and the overexpression of hApg3p facilitates
      the formation of the GFPhApg12p.thApg5p conjugate, suggesting that hApg3p cross
      talks with the hApg12p conjugation system.

PMID- 11825911
TI  - Protein kinase B is regulated in platelets by the collagen receptor glycoprotein
      VI.
AB  - Phosphoinositide 3-kinase (PI3K) is a critical component of the signaling
      pathways that control the activation of platelets. Here we have examined the
      regulation of protein kinase B (PKB), a downstream effector of PI3K, by the
      platelet collagen receptor glycoprotein (GP) VI and thrombin receptors.
      Stimulation of platelets with collagen or convulxin (a selective GPVI agonist)
      resulted in PI3K-dependent, and aggregation independent, Ser(473) and Thr(308)
      phosphorylation of PKBalpha, which results in PKB activation. This was
      accompanied by translocation of PKB to cell membranes. The phosphoinositide
      dependent kinase PDK1 is known to phosphorylate PKBalpha on Thr(308), although
      the identity of the kinase responsible for Ser(473) phosphorylation is less
      clear. One candidate that has been implicated as being responsible for Ser(473)
      phosphorylation, either directly or indirectly, is the integrin-linked kinase
      (ILK). In this study we have examined the interactions of PKB, PDK1, and ILK in
      resting and stimulated platelets. We demonstrate that in platelets PKB is
      physically associated with PDK1 and ILK. Furthermore, the association of PDK1 and
      ILK increases upon platelet stimulation. It would therefore appear that formation
      of a tertiary complex between PDK1, ILK, and PKB may be necessary for
      phosphorylation of PKB. These observations indicate that PKB participates in cell
      signaling downstream of the platelet collagen receptor GPVI. The role of PKB in
      collagen- and thrombin-stimulated platelets remains to be determined.

PMID- 11825912
TI  - Hinge-bending motion of D-allose-binding protein from Escherichia coli: three
      open conformations.
AB  - Conformational changes of periplasmic binding proteins are essential for their
      function in chemotaxis and transport. The allose-binding protein from Escherichia
      coli is, like other receptors in its family, composed of two alpha/beta domains
      joined by a three-stranded hinge. In the previously determined structure of the
      closed, ligand-bound form (Chaudhuri, B. N., Ko, J., Park, C., Jones, T. A., and
      Mowbray, S. L. (1999) J. Mol. Biol. 286, 1519-1531), the ligand-binding site is
      buried between the two domains. We report here the structures of three distinct
      open, ligand-free forms of this receptor, one solved at 3.1-A resolution and two
      others at 1.7-A resolution. Together, these allow a description of the
      conformational changes associated with ligand binding. A few large, coupled
      torsional changes in the hinge strands are sufficient to generate the overall
      bending motion, with only minor disruption of the individual domains. Integral
      water molecules appear to act as structural "ball bearings" in this process. The
      conformational changes of the related ribose-binding protein follow a distinct
      pattern. The observed differences between the two proteins can be interpreted in
      the context of changes in sequence and in crystal packing and provide new
      insights into the nature of hinge bending motion in this class of periplasmic
      binding proteins.

PMID- 11825915
TI  - An organ donor memorial.
AB  - This article describes how a memorial to transplant donors was created in a
      district general hospital. The subjects discussed include: how to start, the
      official ceremony, the value of such a venture to those concerned, finance and
      time involved, a description of the memorial itself, the ongoing promotion of the
      scheme, and the pressing need for organ donors.

PMID- 11825917
TI  - Androgen receptor expression in ductal carcinoma in situ of the breast: relation
      to oestrogen and progesterone receptors.
AB  - AIMS: Ductal carcinoma in situ (DCIS) of the breast has been diagnosed
      increasingly since the advent of mammographic screening. In contrast to the
      situation in invasive breast carcinoma, there are no reports on androgen receptor
      (AR) status in DCIS and few reports on oestrogen (ER) and progesterone (PR)
      receptors. METHODS: AR expression was examined in 57 cases of DCIS of the breast
      and correlated to the degree of differentiation and ER/PR status using
      immunohistochemical methods. RESULTS: AR positivity was noted in 19 of the cases,
      whereas the other 38 cases were negative. There was no significant association
      between AR expression and the degree of differentiation of DCIS; three of the 13
      well differentiated DCIS cases, 10 of the 19 intermediately differentiated cases,
      and six of the 25 poorly differentiated cases were positive (p = 0.093). However,
      a strong association was shown between the expression of ER (p < 0.0001) and PR
      (p = 0.002) and the degree of differentiation of DCIS. In addition, no
      significant association was found between the expression of AR and the expression
      of ER (p = 0.26) or PR (p = 0.57) in DCIS of the breast. CONCLUSIONS: A large
      number of cases of DCIS of the breast express AR and this may be associated with
      apocrine differentiation, which may impact on accurate typing of DCIS. Moreover,
      the expression of AR (but not ER or PR) in DCIS does not appear to be associated
      with the degree of differentiation.

PMID- 11825916
TI  - Cryoglobulins.
AB  - Serum cryoglobulins are found in a wide spectrum of disorders but are often
      transient and without clinical implications. Monoclonal cryoglobulins are usually
      associated with haematological disorders, whereas mixed cryoglobulins are found
      in many infectious and systemic disorders. So called essential mixed
      cryoglobulinaemia shows a striking association with hepatitis C virus (HCV)
      infection (> 90%). It is a systemic vasculitis (leucocytoclastic vasculitis) with
      cutaneous and multiple visceral organ involvement. Chronic HCV infection can lead
      to a constellation of autoimmune and neoplastic disorders. In this review, the
      aetiology, diagnosis, disease heterogeneity, and treatment of cryoglobulinaemia
      are discussed.

PMID- 11825918
TI  - Conclusions from a study of venous invasion in stage IV colorectal
      adenocarcinoma.
AB  - AIMS: Venous invasion is an established predictor of prognosis in colorectal
      cancer (CRC). The reported incidence of venous invasion in CRC specimens varies
      between 10% and 89.5%, mainly as a result of interobserver variability and
      differences in specimen processing (for example, staining with haematoxylin and
      eosin (H+E) alone versus the addition of an elastic fibre stain). This study was
      performed with three purposes in mind, namely: (1) To assess and compare the
      incidence of venous invasion diagnosed on H+E stained tissue versus tissue
      stained with both H+E and an elastic fibre stain. (2) To estimate the inherent
      false negative rate associated with the diagnosis of venous invasion by
      histopathological evaluation of resected CRC specimens. (3) To compare the
      resulting data regarding incidence, quantity, site, and type of venous invasion
      to the pertinent literature. METHODS: Venous invasion was assessed on sections
      from 81 CRCs resected from patients with synchronous distant metastases (hepatic
      and non-hepatic). Only stage IV tumours were studied for the following reasons:
      (1) it can be assumed that in all patients with distant haematogenous metastases
      venous invasion had occurred, thus enabling the false negative rate to be
      calculated; (2) there can be no dispute about the clinical relevance of the
      various characteristics of venous invasion identified in the tumours of patients
      with synchronous distant haematogenous metastases; and (3) to eliminate the
      effect of variance in tumour stage on the incidence of venous invasion.
      Initially, H+E stained sections were studied for venous invasion. Sections that
      were negative or questionable with regard to venous invasion were then stained
      with an elastic fibre stain, and a second search for venous invasion was carried
      out. Venous invasion was characterised by incidence, quantity, type, and site.
      The chi(2) test for independence was used to compare the incidence of venous
      invasion in colonic versus rectal and rectosigmoid primary tumours, and in
      patients with hepatic versus non-hepatic metastases. RESULTS: Venous invasion was
      identified in 42 (51.9%) (of the 81 specimens on H+E stained sections. The
      addition of the elastic fibre stain enabled the diagnosis of venous invasion in
      15 (38.5%) of the remaining 39 specimens, increasing the overall incidence to 57
      of 81 cases (70.4%). Of the 57 positive specimens, venous invasion was minimal in
      27 (47.4%), intermediate in five, (8.8%) and massive in 25 (43.9%). Only
      intramural veins were involved in 18 (31.6%), only extramural veins in 26
      (45.6%), and both intramural and extramural veins in 13 (22.8%) of the 57
      positive specimens. The filling type of venous invasion was found in 41 (71.9%),
      the floating type in 28 (49.1%), and the infiltrating type in six (10.5%) of the
      57 positive specimens. There was no significant difference between the incidence
      of venous invasion in the colon (42 of 60; 70%) versus rectal and rectosigmoid
      tumours (15 of 21; 71.4%; p = 0.8539), nor in the incidence of venous invasion in
      patients with hepatic (49 of 70; 70%) versus non-hepatic (eight of 11; 72.7%)
      metastases (p = 0.9018). CONCLUSIONS: The addition of an elastic fibre stain
      enables the identification of venous invasion in a considerable proportion of
      sections from CRC tumours that are falsely negative for venous invasion on H+E
      stain alone. The inherent chance of missing venous invasion on histopathological
      evaluation of CRC tumours stained with H+E and elastic fibre stains is at least
      10.5%, and may be as high as 29.6%. In a large proportion of stage IV CRCs,
      despite the presence of synchronous distant metastases, only a minimal extent of
      venous invasion (that is, one to two involved veins) is demonstrable in the
      primary tumour. This suggests that only minimal venous invasion is required for
      the seeding of clinically relevant haematogenous metastases, and emphasises the
      careful, dedicated search for venous invasion that is required from the
      pathologist. Although extramural venous invasion was predominant in stage IV
      CRCs, in a considerable proportion of tumours (about a third) only intramural
      venous invasion was found. This suggests that intramural venous invasion may also
      seed clinically relevant haematogenous metastases, and should therefore also be
      considered as an indicator of poor prognosis.

PMID- 11825919
TI  - Telomerase activation and human papillomavirus infection in invasive uterine
      cervical carcinoma in a set of Malaysian patients.
AB  - AIM: Telomerase activity was studied in invasive uterine cervical carcinoma to
      assess whether it was activated during cervical malignant transformation and to
      look for a possible association with human papillomavirus (HPV) infection in a
      set of Malaysian patients. METHODS: Histologically confirmed invasive cervical
      carcinoma and benign cervices were assayed for telomerase activity using a
      commercial telomerase polymerase chain reaction (PCR) enzyme linked immunosorbent
      assay kit. The same cases were subjected to PCR detection of HPV using type
      specific (HPV types 6b, 11, 16, and 18) followed by L1 open reading frame (ORF)
      consensus primers. RESULTS: HPV was detected in 18 (13 HPV-16, one HPV-6b, four
      only L1 ORF) of 20 invasive cervical carcinoma and one (only L1 ORF) of 19 benign
      cervices. Raised telomerase activity (A(450 nm) > 0.215) was detected in 11
      cervical carcinomas, with A(450 nm) ranging between 0.238 and 21.790 (mean,
      3.952) in positive squamous carcinomas, whereas A(450 nm) was only 0.222 in the
      one positive adenosquamous carcinoma. Five of 11 cervical carcinomas in stage I,
      three of six in stage II, both in stage III, and the only case in stage IV showed
      telomerase activation. Increased telomerase activity was noted in five of the 12
      lymph node negative, five of the seven lymph node status unknown cases, and the
      one case with presumed lymph node metastasis. Ten of 18 HPV positive and one of
      two HPV negative cervical carcinomas showed telomerase upregulation. CONCLUSIONS:
      Telomerase is activated in invasive cervical carcinoma. Although larger studies
      are needed, there seems to be no clear association between telomerase
      upregulation and HPV status, although there is a suggestion of increased
      telomerase activity in squamous carcinomas and late stage disease.

PMID- 11825920
TI  - Morphological effects of chemotherapy on ovarian carcinoma.
AB  - AIMS: Traditionally, advanced stage ovarian carcinoma is treated by debulking
      surgery followed by chemotherapy. However, in some circumstances preoperative
      chemotherapy may be given before optimal surgical debulking. This study aims to
      describe the morphological features found in ovarian carcinoma after chemotherapy
      because these have not been detailed previously. METHODS: Histological sections
      were examined from 18 cases of ovarian carcinoma that had been treated by
      preoperative chemotherapy. The morphology was compared with any pre-chemotherapy
      biopsies that had been performed. Tumours were classified as showing
      morphological features suggesting a good response to chemotherapy (n = 14) or as
      showing little or no response (n = 4). Serum CA125 values before and after
      chemotherapy were compared. In all cases, the mitotic activity index (MAI),
      volume percentage of epithelium (VPE), and mean nuclear area (MNA) of tumour
      cells were calculated. RESULTS: The preoperative biopsies were all typical
      ovarian serous or endometrioid adenocarcinomas. Morphological features present in
      the group responding to chemotherapy included the presence of small groups or
      single tumour cells in a densely fibrotic stroma. Tumour cells were characterised
      by both nuclear and cytoplasmic alteration, making accurate tumour typing and
      grading impossible. Nuclear features included the presence of bizarre enlargement
      with hyperchromatism, irregularity of outline, and chromatin clumping or
      smudging. Cytoplasmic alterations included intense eosinophilia, vacuolation, or
      foam cell change. There were pronounced stromal changes of fibrosis,
      inflammation, collections of foamy histiocytes, cholesterol cleft formation,
      haemosiderin deposition, fat necrosis, and dystrophic calcification, including
      the presence of many free psammoma bodies. There was no correlation between
      morphological response and biochemical response, as determined by serum CA125
      values. In all nine cases in which pre-chemotherapy and post-chemotherapy
      biopsies were available, the MNA increased post-chemotherapy (p = 0.007, paired
      Wilcoxon test) and in six of nine cases the MAI decreased (p = 0.093).
      CONCLUSIONS: Because preoperative chemotherapy is being used increasingly in the
      management of ovarian cancer, pathologists should be aware of the resultant
      morphological effects. Accurate tumour typing and grading is impossible. In some
      cases, it may be difficult to confirm the presence of residual tumour, making it
      imperative that pre-chemotherapy tissue biopsies are obtained. Definite
      confirmation of residual tumour may require the examination of multiple
      histological sections from areas showing pronounced stromal changes, sometimes
      with multiple levels and immunohistochemistry. In the absence of definite
      residual tumour, the report should state that the features are consistent with
      the prior presence of tumour.

PMID- 11825921
TI  - Laboratory confirmation of meningococcal disease in Scotland, 1993-9.
AB  - AIMS: To describe the laboratory confirmation of meningococcal disease, using
      culture and non-culture based techniques, between 1993 and 1999 as part of a
      national service in Scotland. METHODS: Samples from patients with suspected
      meningococcal disease in Scotland were analysed by culture and non-culture based
      techniques to gain a laboratory confirmation of disease. Data were analysed to
      establish the number of disease cases, the serogroups of the organisms involved,
      and the importance of the techniques used. RESULTS: Between 1993 and 1999, there
      was a total of 1749 notified cases of meningococcal disease in Scotland. Culture
      based methods provided a laboratory confirmation of 788 cases whereas non-culture
      techniques confirmed 461 cases. CONCLUSIONS: Non-culture techniques were a useful
      addition to culture based techniques in Scotland and improved the dataset
      required for public health management, disease surveillance, and vaccine policy.

PMID- 11825922
TI  - Ultrasound enhanced detection of individual meningococcal serogroups by latex
      immunoassay.
AB  - AIMS: To examine A, C, Y, and W135 Neisseria meningitidis serogroup
      characterisation by ultrasonic standing wave enhanced latex agglutination tests
      (USELATs) of clinical samples. In addition, to determine USELAT enhancement of
      detection sensitivity for the individual antigens compared with conventional card
      latex agglutination tests (LATs). METHODS: Wellcogen (Abbott Murex), Slidex
      meningite kit 5 (bioMerieux), and Pastorex (Sanofi) kits and beads coated in
      house with antibodies to Y and to W135 alone were tested. Positive control
      antigens consisted of A and C polysaccharide preparations and the Pastorex Y/W135
      kit sample. The limiting concentrations of antigen detection were determined by
      USELAT and by LAT. Thirty five clinical samples (plasma), previously
      characterised by the polymerase chain reaction (PCR) and culture, were tested by
      USELAT and, when sample volume allowed, by LAT. RESULTS: USELAT enhancement of
      control antigen detection ranged from 16 to 128 fold for the different latex
      systems. Enhancements for the different control antigens were comparable between
      kits. USELAT tests of clinical (A/C/Y/W135) samples (n = 15) with the Wellcogen
      (A/C/Y/W135) and Slidex meningite (A/C/Y/W135) kits showed comparable
      specificities. A set (n = 22) of Y and W135 samples gave 18, 19, and 17 positive
      results for Wellcogen (A/C/Y/W135), Pastorex (A/C/Y/W135), and in house beads
      (Y/W135), respectively. Positive USELAT PCR and culture results were concordant.
      A typical sensitivity for the commercial kits was 80% (Wellcogen). CONCLUSIONS:
      USELAT identified serogroups for 80% of samples, whereas LATs identified only
      40%. The USELAT detection of the A, C, Y, and W135 antigen serogroups showed
      comparable enhancement for the kits tested. The commercial availability of latex
      beads coated with antibody to the Y and W135 serogroups would expedite their
      identification.

PMID- 11825923
TI  - A rapid ELISA for the diagnosis of intravascular catheter related sepsis caused
      by coagulase negative staphylococci.
AB  - AIM: To develop and evaluate a rapid enzyme linked immunosorbent assay (ELISA)
      for the diagnosis of intravascular catheter related sepsis caused by coagulase
      negative staphylococci. METHODS: Forty patients with a clinical and
      microbiological diagnosis of intravascular catheter related sepsis and positive
      blood cultures, caused by coagulase negative staphylococci, and 40 control
      patients requiring a central venous catheter as part of their clinical management
      were recruited into the study. Serum IgG responses to a previously undetected
      exocellular antigen produced by coagulase negative staphylococci, termed lipid S,
      were determined in the patient groups by a rapid ELISA. RESULTS: There was a
      significant difference (p = < 0.0001) in serum IgG to lipid S between patients
      with catheter related sepsis and controls. The mean antibody titre in patients
      with sepsis caused by coagulase negative staphylococci was 10 429 (range, no
      detectable serum IgG antibody to 99 939), whereas serum IgG was not detected in
      the control group of patients. CONCLUSIONS: The rapid ELISA offers a simple,
      economical, and rapid diagnostic test for suspected intravascular catheter
      related sepsis caused by coagulase negative staphylococci, which can be difficult
      to diagnose clinically. This may facilitate treatment with appropriate
      antimicrobials and may help prevent the unnecessary removal of intravascular
      catheters.

PMID- 11825925
TI  - Discriminant histological features in the diagnosis of chronic idiopathic
      inflammatory bowel disease: analysis of a large dataset by a novel data
      visualisation technique.
AB  - BACKGROUND/AIMS: The histopathological assessment of endoscopic colorectal
      biopsies is important in the distinction between normality and chronic idiopathic
      inflammatory bowel disease, and between ulcerative colitis and Crohn's disease,
      in subjects with symptoms of bowel dysfunction. This study aims to use carefully
      defined histopathological observations on a large study population to produce
      systems that improve classification into these diagnostic categories. METHODS:
      Eight hundred and nine endoscopic colorectal biopsies with verified outcomes (165
      normal, 473 ulcerative colitis, 171 Crohn's disease) were examined by a single
      experienced histopathologist and 20 defined features were recorded for each case
      using a novel graphical interface with reference images of each feature. These
      features, together with age and sex, were used to produce and test statistical
      classifiers using logistic regression and a novel growing cell structure
      technique. RESULTS: The distinction between chronic idiopathic inflammatory bowel
      disease and normality was made with a good level of performance by both
      statistical classifiers (with areas under the receiver operating characteristic
      curves above 0.80). The growing cell structure system selected features as
      discriminant that agreed with the published literature. Logistic regression
      produced a more variable selection of discriminant features because of the high
      correlation between many features. The distinction between ulcerative colitis and
      Crohn's disease was performed less accurately, with areas under the receiver
      operating characteristic curves of about 0.70. Again the features selected as
      discriminant broadly agreed with those in the published literature. CONCLUSIONS:
      Histopathological examination of endoscopic colorectal biopsies is an effective
      method of distinguishing between subjects with chronic idiopathic inflammatory
      bowel disease and normality, but less good at distinguishing between ulcerative
      colitis and Crohn's disease. The features selected as discriminant in this large
      statistical analysis broadly agree with those published in the literature from
      more qualitative studies.

PMID- 11825924
TI  - Sudden unexplained death in adults caused by intracranial pathology.
AB  - Sudden unexplained deaths as a result of intracranial lesions in adults are an
      important component of medicolegal practice and are best examined as a combined
      effort by a forensic pathologist, or a histopathologist experienced in coroner's
      necropsies, and a neuropathologist. Analysis of case material on file in the
      University of Glasgow's departments of forensic medicine and science, and
      neuropathology showed that the principal causes were sudden unexplained death in
      epilepsy (SUDEP), intracranial haemorrhage, either natural or after trauma,
      purulent meningitis or an abscess, and tumours. The mechanisms of death are
      considered to be the rapid increase of intracranial pressure caused by bleeding
      into the various compartments of the brain, or an acute obstructive
      hydrocephalus, and in cases where death is very rapid, autonomic and/or
      neurochemical dysfunction.

PMID- 11825926
TI  - Clinicopathological significance of p16 gene expression in the surgical treatment
      of head and neck squamous cell carcinomas.
AB  - AIMS: To evaluate the clinicopathological significance of p16 expression in the
      surgical management of squamous cell carcinomas of the oral cavity, oropharynx,
      hypopharynx, and larynx. METHOD: p16 expression in 225 head and neck squamous
      cell carcinomas (HNSCCs) was studied using an immunohistochemical method and
      paraffin wax embedded tumour tissues. Associations between p16 expression and
      clinicopathological features were investigated. RESULTS: Decreased p16 expression
      was found in 48% of the tumours. There was a higher frequency of decreased p16
      expression in tumours of the larynx compared with those from the pharynx and oral
      cavity. There was a significant correlation between decreased p16 expression and
      more advanced T stage. There was no significant correlation between p16
      expression and sex, age, tumour grade, nodal metastasis, recurrence, or survival.
      CONCLUSION: There was a high frequency of downregulation of p16 expression in
      HNSCC. Tumours of the larynx had a significantly higher frequency of weak p16
      expression compared with tumours of the oral cavity and pharynx. Downregulation
      of p16 contributed to cellular proliferation, resulting locally in a more
      advanced tumour. It had no prognostic significance for nodal metastasis and
      survival.

PMID- 11825927
TI  - Primary T cell lymphoma of salivary gland: a report of a case and review of the
      literature.
AB  - Lymphoma of the salivary gland accounts for 5% of cases of extranodal lymphoma
      and 10% of malignant salivary gland tumours. Most primary salivary gland
      lymphomas are B marginal zone lymphomas arising on a background of sialadenitis
      associated with autoimmune disorders such as Sjorgen's syndrome. Primary T cell
      lymphoma of the salivary gland is rare. This report describes a case of primary T
      cell lymphoma arising in the parotid gland of an elderly white man, which was
      notable for its striking resemblance to a B cell extranodal marginal zone
      lymphoma. Immunohistochemistry and gene rearrangement studies confirmed the
      clonal T cell nature of the tumour. There was no molecular evidence of Epstein
      Barr virus (EBV) infection of neoplastic or surroundings cells. Only 14 cases of
      primary T cell lymphoma of the salivary glands have been recorded in the
      literature, most being from the Orient and having extremely variable prognosis.
      Those with a T/natural killer cell phenotype are associated with EBV infection.
      This case highlights the fact that T cell lymphoma in the salivary gland can
      mimic closely the morphological features of B cell extranodal marginal zone
      lymphoma.

PMID- 11825928
TI  - Anti-D immunoglobulin treatment for thrombocytopenia associated with primary
      antibody deficiency.
AB  - AIMS: To review our experience of anti-D immunoglobulin for immune
      thrombocytopenia (ITP) in patients with primary antibody deficiency.
      METHODS/PATIENTS: A retrospective case notes review of four Rhesus positive
      patients with ITP and primary antibody deficiency, treated with anti-D. Patients
      were refractory to steroids and high dose intravenous immunoglobulin (IVIG). Two
      patients were previously splenectomised. RESULTS: All patients responded to anti
      D immunoglobulin. Improved platelet counts were sustained for at least three
      months. Side effects included a fall in haemoglobin in all cases; one patient
      required red blood cell transfusion. Two patients had transient neutropenia (< 1
      x 10(9)/litre). CONCLUSION: Anti-D immunoglobulin may be an effective treatment
      for antibody deficiency associated thrombocytopenia, even after splenectomy. Anti
      D immunoglobulin may have considerable clinical advantages in this group of
      patients, where treatments resulting in further immunosuppression are relatively
      contraindicated.

PMID- 11825929
TI  - Is microscopic assessment of macroscopically normal hysterectomy specimens
      necessary?
AB  - AIM: To determine whether microscopic examination of macroscopically normal
      hysterectomy specimens yields findings that could alter subsequent clinical
      management. METHODS: All pathology reports on hysterectomy specimens submitted to
      the department of histopathology at the Northern General Hospital from January
      1997 to December 1998 were reviewed. Cases were included for further assessment
      if the hysterectomy specimen was regarded as macroscopically normal by a
      consultant pathologist and if the patient had no history of, or suspicion of,
      neoplastic disease. The subsequent microscopic findings from these cases were
      assessed to determine whether any lesions of clinical importance were identified.
      RESULTS: Eight hundred and fifty four specimens were reviewed, of which 139 were
      suitable for inclusion. Only one of the 139 cases harboured a microscopic
      abnormality that necessitated specific clinical follow up; this was a focus of
      cervical intraepithelial neoplasia 2 (CIN 2). On follow up of that patient, no
      further neoplastic disease was identified. CONCLUSION: Microscopic assessment of
      macroscopically normal hysterectomy specimens does not contribute to patient
      management and is unnecessary in an era of manpower shortage and cost
      containment.

PMID- 11825931
TI  - How should the chest wall be opened at necropsy?
AB  - AIMS: To compare several different instruments used to open the chest wall during
      necropsy and to assess whether any one type reduced the production of sharp rib
      ends and thus the potential for receiving an injury. METHODS: During the necropsy
      the pathologist opened the chest wall using two randomly assigned instruments
      from a selection of hand saw, electric saw, rib shears, and bread knife. The age,
      weight, sex, and height of the deceased were recorded, in addition to the
      textures of the resultant exposed rib ends. During the procedure, the speed,
      length, production of spray, and site of incision were also noted. The thoracic
      cavity was inspected and any details of tumours, adhesions, fluid, or organ
      damage were noted. RESULTS: Twenty four necropsies were carried out on an equal
      number of men and women. The total number of ribs that were incised was 422, with
      206 through the bony aspect (49%). Sixty seven per cent of the bony rib ends were
      rough, and this was found to be instrument dependent. The rib shears produced the
      highest number of rough bony and cartilage rib ends. The electric saw produced
      the smoothest contoured rib ends. Spray occurred in 29% of cases, exclusively
      with the use of the electric saw. Organ damage was most frequently associated
      with the use of the bread knife. CONCLUSION: Rib shears, the instrument most
      frequently used to open the chest wall, appear to cause the highest frequency of
      rough, potentially dangerous rib ends. The electric saw produced the smoothest
      rib ends, both in cartilage and bone, and thus seems to offer the most
      efficacious method of reducing the potential hazard associated with ragged, spiky
      bone ends during the opening of the thoracic cavity. Although each of the
      procedures detailed in this study was shown to have its own advantages and
      disadvantages, personal preference and operator experience are perhaps the most
      important factors in ultimately determining the method used.

PMID- 11825930
TI  - New criteria for the differentiation between transudates and exudates.
AB  - AIMS: To investigate whether cholesterol and lactate dehydrogenase (LDH)
      measurements in fluids are more sensitive and specific markers for
      differentiating between exudates and transudates, as confirmed clinically, than
      the measurement of fluid total protein concentrations alone. PATIENTS/METHODS:
      Serum, pleural fluid, and ascitic fluid from 61 unselected patients were analysed
      retrospectively for LDH, cholesterol, and total protein. Clinical classification
      of transudate or exudate was reached independently by reviewing clinical details
      and laboratory data. RESULTS: Of 54 samples (40 pleural fluid and 14 ascitic
      fluid), 30 were classified clinically as exudates and 24 as transudates. Fluid
      LDH and fluid to serum protein ratio measurements were equally good at
      differentiating between exudates and transudates, with a sensitivity of 90%, a
      specificity of 79%, a positive predictive value (PPV) of 84%, and a negative
      predictive value (NPV) of 86%. A combination of these parameters improved
      sensitivity to 100% and NPV to 100%, but lowered the specificity to 71% and PPV
      to 81%. This combination achieved a higher efficiency than Light's criteria.
      CONCLUSION: Routine measurement of fluid LDH values and the calculation of fluid
      to serum total protein ratios will aid in differentiating exudates from
      transudates.

PMID- 11825932
TI  - Microinvasive lobular carcinoma associated with intraductal spread arising in a
      mammary hamartoma.
AB  - A 53 year old woman presented with a lump in the inner lower quadrant of the left
      breast. Histological examination of the breast tumour confirmed that the lesion
      was a mammary hamartoma. Carcinoma with foci of microinvasion was observed in the
      lobules of the hamartoma concomitant with the intraductal spread of lobular
      carcinoma. Immunohistochemically, the cancer cells were negative for beta
      catenin, which generally stained normal breast ducts and ductal carcinomas. This
      is only the sixth case of breast carcinoma arising in a mammary hamartoma to be
      reported and, moreover, the fourth case of lobular carcinoma occurring within a
      hamartoma. Despite the apparent rarity of this case, pathologists should be aware
      of the possibility of carcinomas arising within mammary hamartomas.

PMID- 11825933
TI  - Unnecessary repeat requesting of tests in a university teaching hospital
      immunology laboratory: an audit.

PMID- 11825934
TI  - Detection of HHV-8 in reactive lymphoid tissue of patients from Sao Paulo state,
      Brazil.

PMID- 11825935
TI  - Small cell melanoma.

PMID- 11825936
TI  - Laboratory testing for Lyme disease: possibilities and practicalities.

PMID- 11825937
TI  - Highly sensitive assay for human herpesvirus 8 antibodies that uses a multiple
      antigenic peptide derived from open reading frame K8.1.
AB  - The immunodominant region of the human herpesvirus 8 (HHV-8), the antibody
      binding site of glycoprotein K8.1A, was mapped to the N-terminal region by using
      overlapping peptides and a residue replacement method. The main epitope was
      located within residues 44 to 56 (GQVYQDWL----C). Based on this information, we
      developed an enzyme immunoassay to detect HHV-8 antibodies in human sera using a
      four-branch multiple antigenic peptide as the antigen. The sensitivity and
      specificity of the assay were 96 and 99.4%, respectively. This assay should be
      useful for population-based, epidemiological studies of HHV-8 infection.

PMID- 11825938
TI  - Role of picornaviruses in flu-like illnesses of adults enrolled in an oseltamivir
      treatment study who had no evidence of influenza virus infection.
AB  - The primary objective of this study was to determine the role of picornavirus in
      flu-like episodes (temperature of > or =38.0 degrees C plus one respiratory and
      one constitutional symptom) among otherwise healthy adults enrolled in a placebo
      controlled, double-blind, randomized oseltamivir treatment study. Combined nasal
      and pharyngeal swabs were collected at baseline for influenza cultures and
      picornavirus reverse transcription (RT)-PCR. In addition, acute- and convalescent
      serum samples were obtained for serological studies of common respiratory
      pathogens. From a total of 719 subjects enrolled in the clinical trial within 36
      h of the onset of symptoms, 475 (66%) had evidence of recent influenza A or B
      virus infections by means of culture and/or serological testing. Of the 244
      remaining patients, 36 (15%) presented a seroconversion for at least one of the
      common respiratory viruses or atypical pathogens. An RT-PCR assay for the
      picornavirus 5" noncoding region (NCR) was positive in a subset of 15 (19%) of 78
      patients with flu-like illnesses of undetermined etiology. Sequence analysis of
      the picornavirus 5" NCR amplicons revealed that 14 (93%) of them had greater
      homology to rhinoviruses, whereas 1 (7%) was related to enteroviruses.
      Interestingly, median total symptom scores and oral temperatures of picornavirus
      positive patients (n = 15) and placebo-treated influenza virus-positive patients
      (n = 161) were similar over a 3-week period. We conclude that, among the
      influenza virus-negative preselected cases of this study, rhinoviruses were
      relatively frequent pathogens associated with important respiratory and systemic
      symptoms.

PMID- 11825939
TI  - Discordance between genotypic and phenotypic drug resistance profiles in human
      immunodeficiency virus type 1 strains isolated from peripheral blood mononuclear
      cells.
AB  - The aim of the study was to analyze the relationship between genotypic and
      phenotypic drug resistance profiles of human immunodeficiency virus type 1 (HIV
      1) strains isolated from patients during double-analogue nucleoside therapy. A
      drug-resistant HIV strain was isolated from 20 out of 25 patients, with 16 (64%)
      subjects carrying a virus with multiple drug resistance mutations. The most
      frequent resistance mutations were M184V (18 isolates) and M41L (7 isolates).
      Discordance between the genotypic and phenotypic profile for at least one drug
      was detected in 16 out of 25 strains. Particularly, eight isolates had a
      discordant genotypic-phenotypic resistance pattern for two drugs and one isolate
      had such a pattern for three drugs. A genotypic resistance pattern with a
      phenotypic sensitivity profile was detected in six isolates (four resistant to
      zidovudine and two resistant to lamivudine). On the other hand for several
      strains a genotypic pattern of sensitivity pattern to abacavir (10 strains),
      didanosine (7 strains), stavudine (3 strains), zidovudine (2 strains), and
      lamivudine (1 strain) with a phenotypic resistance profile was detected. After a
      follow-up period of 8 months, an impairment of virological and immunological
      parameters was detected only in subjects with an HIV-1 isolate with a phenotypic
      resistance profile in despite of the genotypic results. Predicting resistance
      phenotype from genotypic data has important limitations. Despite the low number
      of patients and the short follow-up period, this study suggests that during
      failing therapy with analogue nucleosides, a phenotypic analysis could be
      performed in spite of an HIV genotypic sensitivity pattern.

PMID- 11825940
TI  - Carriage frequency, intensity of carriage, and strains of oral yeast species vary
      in the progression to oral candidiasis in human immunodeficiency virus-positive
      individuals.
AB  - Candida samples were taken over a period of 2 years from 54 human
      immunodeficiency virus (HIV)-positive asymptomatic subjects to evaluate changes
      in yeast carriage, intensity of carriage, and genotype over time. Overall, we
      found that HIV-positive patients with CD4(+)-cell counts of between 200 and
      400/microl had significantly more yeast colonization than healthy control
      subjects. Of the 54 patients, 11 developed thrush. We found that intensity of
      carriage in these 11 patients increased significantly in the progression from
      asymptomatic yeast carrier to an episode of oral thrush. Also, the most common
      yeast species isolated was Candida albicans; however, we did see a number of
      patients harboring multiple species at the same time. Using the C. albicans
      specific probe Ca3, we found that 54% (n = 6) of the 11 patients who developed
      thrush maintained genetically similar strains throughout the study period, with
      minor genetic variations in all patients except one. Forty-six percent of these
      patients had either multiple strains throughout the study period (n = 2), strain
      replacement (n = 1), or species replacement (n = 2). Of the patients who had
      multiple strains, one (I4) was infected by two different strains of Candida
      dubliniensis distinguished by a recently developed species-specific probe. These
      results suggest that commensal strains colonizing HIV-positive individuals can
      undergo alterations prior to producing an episode of thrush.

PMID- 11825941
TI  - Evaluation of use of Epstein-Barr viral load in patients after allogeneic stem
      cell transplantation to diagnose and monitor posttransplant lymphoproliferative
      disease.
AB  - Epstein-Barr virus (EBV)-induced posttransplant lymphoproliferative disease
      (PTLD) continues to be a serious complication following transplantation. The aim
      of the present study was to evaluate the EBV load as a parameter for the
      prediction and monitoring of PTLD. The EBV load was analyzed by a quantitative
      competitive PCR with 417 whole-blood samples of 59 patients after allogeneic stem
      cell transplantation (SCT). The EBV load was positive for all 9 patients with
      PTLD and for 17 patients without PTLD. The viral loads of patients with manifest
      PTLD differed from the loads of those without PTLD (median loads, 1.4 x 10(6)
      versus 4 x 10(4) copies/microg of DNA; P < 0.0001). A threshold value of 10(5)
      copies/microg of DNA showed the best diagnostic efficacy (sensitivity, 87%;
      specificity, 91%). However, in patients with less than three major risk factors
      for PTLD, the positive predictive value of this threshold was rather low. One
      week prior to the manifestation of PTLD, the EBV load was as low in patients who
      developed PTLD as in patients without disease (median, 2.2 x 10(4) copies/microg
      of DNA; P was not significant). EBV DNA tested positive first at 20 to 71 days
      prior to the clinical manifestation of PTLD and occurred with the same delay
      after transplantation regardless of disease (median delay, 52 versus 63 days; P
      was not significant). EBV DNA was detected earlier in patients with primary
      infections than in those with reactivations (33 versus 79 days; P = 0.01), but
      the peak levels were similar in the two groups. EBV primary infection or EBV
      reactivation is frequent in patients after allogeneic SCT but results in PTLD
      only in a subgroup of patients. Although evaluation of the EBV load has
      limitations, the EBV load represents a valuable parameter to guide therapy.

PMID- 11825942
TI  - Paracoccidioides brasiliensis 87-kilodalton antigen, a heat shock protein useful
      in diagnosis: characterization, purification, and detection in biopsy material
      via immunohistochemistry.
AB  - The 87-kDa antigen derived from the fungal pathogen Paracoccidioides brasiliensis
      can be detected in the sera of infected patients, and its levels have been shown
      to correlate well with response to treatment and with clinical cure. Despite its
      potential importance, the antigen has been poorly characterized. The 87-kDa
      antigen was purified to homogeneity via preparative gel electrophoresis; N
      terminal amino acid sequencing revealed substantial homology with heat shock
      proteins (hsps) from a variety of organisms. A monoclonal antibody (MAb) raised
      against a Histoplasma capsulatum 80-kDa hsp showed cross-reactivity to the
      purified 87-kDa antigen via Western blotting, and the 87-kDa-specific MAb P1B
      demonstrated that the antigen was expressed at higher levels in yeast than in
      mycelia by the same technique. Enzyme-linked immunosorbent assay and
      immunofluorescence reactivity using P1B confirmed increased expression of the 87
      kDa antigen during the temperature-induced transformation of mycelia to yeast.
      Yeast-to-mycelium transformation was accompanied by a fall in expression,
      although the 87-kDa antigen was clearly constitutively expressed in both phases.
      Immunochemical staining of tissues from patients with MAb P1B who were infected
      with P. brasiliensis confirmed in vivo expression of the 87-kDa antigen by
      yeasts, and identification of this antigen via this method appears to be a useful
      adjunct to other methods used to diagnose paracoccidioidomycosis.

PMID- 11825943
TI  - Engineered BGMK cells for sensitive and rapid detection of enteroviruses.
AB  - Decay-accelerating factor (DAF) has been reported to be a cellular receptor for
      several enteroviruses. Buffalo green monkey kidney (BGMK) cells expressing human
      DAF (BGMK-hDAF cells) showed increased susceptibility and sensitivity to several
      types of enteroviruses compared to wild-type BGMK cells. When 17 frozen positive
      clinical samples were tested, BGMK cells detected 8 and BGMK-hDAF cells detected
      16. Since the CaCo-2 cell line has been documented to support the replication of
      most enteroviruses, CaCo-2 cells were mixed with BGMK-hDAF cells in order to
      increase the number of viruses detected. Thirty-four frozen clinical samples that
      previously had tested positive for enteroviruses were tested, and the following
      numbers were detected: 33 of 34 by CaCo-2/BGMK-hDAF cells, 29 of 34 by CaCo
      2/BGMK cells, 28 of 34 by H292/RD (E-mix A) and A-549/BGMK (E-mix B) cells, and
      26 of 34 by MRC-5 and pRhMK cells.

PMID- 11825944
TI  - Immunofluorescence technique using HeLa cells expressing recombinant
      nucleoprotein for detection of immunoglobulin G antibodies to Crimean-Congo
      hemorrhagic fever virus.
AB  - A HeLa cell line continuously expressing recombinant nucleoprotein (rNP) of the
      Crimean-Congo hemorrhagic fever virus (CCHFV) was established by transfection
      with an expression vector containing the cDNA of CCHFV NP (pKS336-CCHFV-NP).
      These cells were used as antigens for indirect immunofluorescence (IF) to detect
      immunoglobulin G antibodies to CCHFV. The sensitivity and specificity of this IF
      technique were examined by using serum samples and were compared to those of the
      IF technique using CCHFV-infected Vero E6 cells (authentic antigen). Staining of
      the CCHFV rNP expressed in HeLa cells showed a unique granular pattern similar to
      that of CCHFV-infected Vero E6 cells. Positive staining could easily be
      distinguished from a negative result. All 13 serum samples determined to be
      positive by using the authentic antigen were also determined to be positive by
      using CCHFV rNP-expressing HeLa cells (recombinant antigen). The 108 serum
      samples determined to be negative by using the authentic antigen were also
      determined to be negative by using the recombinant antigen. Thus, both the
      sensitivity and the specificity of this IF technique were 100% compared to the IF
      with authentic antigen. The novel IF technique using CCHFV rNP-expressing HeLa
      cells can be used not only for diagnosis of CCHF but also for epidemiological
      studies on CCHFV infections.

PMID- 11825945
TI  - Enzyme-linked immunosorbent assay specific to Dengue virus type 1 nonstructural
      protein NS1 reveals circulation of the antigen in the blood during the acute
      phase of disease in patients experiencing primary or secondary infections.
AB  - During flavivirus infection in vitro, nonstructural protein NS1 is released in a
      host-restricted fashion from infected mammalian cells but not vector-derived
      insect cells. In order to analyze the biological relevance of NS1 secretion in
      vivo, we developed a sensitive enzyme-linked immunosorbent assay (ELISA) to
      detect the protein in the sera of dengue virus-infected patients. The assay was
      based on serotype 1 NS1-specific mouse and rabbit polyclonal antibody
      preparations for antigen immunocapture and detection, respectively. With purified
      dengue virus type 1 NS1 as a protein standard, the sensitivity of our capture
      ELISA was less than 1 ng/ml. When a panel of patient sera was analyzed, the NS1
      antigen was found circulating from the first day after the onset of fever up to
      day 9, once the clinical phase of the disease is over. The NS1 protein could be
      detected even when viral RNA was negative in reverse transcriptase-PCR or in the
      presence of immunoglobulin M antibodies. NS1 circulation levels varied among
      individuals during the course of the disease, ranging from several nanograms per
      milliliter to several micrograms per milliliter, and peaked in one case at 50
      microg/ml of serum. Interestingly, NS1 concentrations did not differ
      significantly in serum specimens obtained from patients experiencing primary or
      secondary dengue virus infections. These findings indicate that NS1 protein
      detection may allow early diagnosis of infection. Furthermore, NS1 circulation in
      the bloodstream of patients during the clinical phase of the disease suggests a
      contribution of the nonstructural protein to dengue virus pathogenesis.

PMID- 11825946
TI  - The ica operon and biofilm production in coagulase-negative Staphylococci
      associated with carriage and disease in a neonatal intensive care unit.
AB  - Coagulase-negative staphylococci (CoNS) are a major cause of sepsis in the
      neonatal intensive care unit (NICU). We evaluated the hypothesis that the ica
      operon and biofilm production are associated with CoNS disease in this setting.
      CoNS associated with bacteremia or blood culture contamination and from the skin
      of infants with CoNS bacteremia or healthy controls were obtained during a
      prospective case-control study on a busy NICU. A total of 180 strains were
      identified, of which 122 (68%) were Staphylococcus epidermidis and the remainder
      were S. capitis (n = 29), S. haemolyticus (n = 11), S. hominis (n = 9), S.
      warneri (n = 8), and S. auricularis (n = 1). The presence of the genes icaA,
      icaB, icaC, and icaD was determined by PCR, and biofilm production was examined
      using qualitative (Congo red agar [CRA]) and quantitative (microtiter plate)
      techniques. There were no significant differences in the presence of the ica
      operon or CRA positivity among the four groups of strains. However, quantitative
      biofilm production was significantly greater in strains isolated from either the
      blood or the skin of neonates with S. epidermidis bacteremia. We conclude that
      the quantity of biofilm produced may be associated with the ability to cause CoNS
      infection. This conclusion suggests that the regulation of biofilm expression may
      play a central role in the disease process.

PMID- 11825947
TI  - Characterization of chloramphenicol resistance in beta-hemolytic Escherichia coli
      associated with diarrhea in neonatal swine.
AB  - Ninety beta-hemolytic Escherichia coli isolates associated with diarrhea in
      neonatal pigs from multiple farms in Oklahoma were investigated for known
      associated disease serotypes, virulence factors, ribotypes, and antimicrobial
      susceptibility phenotypes. Fifteen different serotypes were observed, with 58% of
      isolates belonging to groups that produce one of three major enterotoxins: O149,
      O147, and O139. Thirty percent of the swine E. coli isolates possessed a
      combination of F4 fimbriae and the heat-labile toxin and heat-stable toxin B
      enterotoxins. Seventy-three percent of the E. coli isolates were resistant to
      five or more antibiotics. Interestingly, 53% of swine E. coli isolates exhibited
      resistance to chloramphenicol (CHL), an antibiotic whose use in food animals has
      been prohibited in the United States since the mid-1980s. The cmlA gene, which
      encodes a putative CHL efflux pump, was detected by PCR in 47 of the 48 CHL
      resistant isolates, and 4 of these also possessed the cat2 gene, which encodes a
      chloramphenicol acetyltransferase. The one CHL-resistant isolate that did not
      contain either cmlA or cat-2 possessed the flo gene, which confers resistance to
      both florfenicol and CHL. To determine whether CHL-resistant swine E. coli
      isolates represented dissemination of a clonal strain, all 90 isolates were
      analyzed by ribotyping. Seventeen distinct E. coli ribogroups were identified,
      with CHL resistance observed among the isolates in all except one of the major
      ribogroups. The identification of the cmlA gene among diverse hemolytic
      enterotoxigenic E. coli strains demonstrates its broad dissemination in the swine
      production environment and its persistence even in the absence of CHL selection
      pressure.

PMID- 11825948
TI  - Rapidly increasing prevalence of penicillin-resistant Streptococcus pneumoniae in
      middle Tennessee: a 10-year clinical and molecular analysis.
AB  - The clinical and molecular epidemiology of penicillin-resistant Streptococcus
      pneumoniae and the diagnostic accuracy of a six-primer PCR assay in identifying
      penicillin resistance were analyzed by using clinical isolates recovered over a
      10-year period in middle Tennessee. The prevalence of non-penicillin-susceptible
      S. pneumoniae isolates (MIC, > or =0.1 microg/ml) increased from 10% in 1990 to
      70% in 1999 (P < 0.001). Among S. pneumoniae isolates for which the penicillin
      MIC was > or =2 microg/ml (highly penicillin-resistant S. pneumoniae [PRSP]), 23
      and 5% were resistant to at least three and at least five other antimicrobial
      classes, respectively. Pulsed-field gel electrophoresis identified 13 unique
      strain types, with type B accounting for 33% of PRSP isolates. The sensitivity,
      specificity, and negative and positive predictive values of the PCR assay in
      detecting PRSP were 99, 100, 99, and 100%, respectively. Penicillin resistance is
      rapidly increasing among S. pneumoniae isolates in Tennessee. The simultaneous
      detection of S. pneumoniae and high-level penicillin resistance can be accurately
      performed with the six-primer PCR assay.

PMID- 11825949
TI  - Identification of Mycobacterium spp. by using a commercial 16S ribosomal DNA
      sequencing kit and additional sequencing libraries.
AB  - Current methods for identification of Mycobacterium spp. rely upon time-consuming
      phenotypic tests, mycolic acid analysis, and narrow-spectrum nucleic acid probes.
      Newer approaches include PCR and sequencing technologies. We evaluated the
      MicroSeq 500 16S ribosomal DNA (rDNA) bacterial sequencing kit (Applied
      Biosystems, Foster City, Calif.) for its ability to identify Mycobacterium
      isolates. The kit is based on PCR and sequencing of the first 500 bp of the
      bacterial rRNA gene. One hundred nineteen mycobacterial isolates (94 clinical
      isolates and 25 reference strains) were identified using traditional phenotypic
      methods and the MicroSeq system in conjunction with separate databases. The
      sequencing system gave 87% (104 of 119) concordant results when compared with
      traditional phenotypic methods. An independent laboratory using a separate
      database analyzed the sequences of the 15 discordant samples and confirmed the
      results. The use of 16S rDNA sequencing technology for identification of
      Mycobacterium spp. provides more rapid and more accurate characterization than do
      phenotypic methods. The MicroSeq 500 system simplifies the sequencing process
      but, in its present form, requires use of additional databases such as the
      Ribosomal Differentiation of Medical Microorganisms (RIDOM) to precisely identify
      subtypes of type strains and species not currently in the MicroSeq library.

PMID- 11825950
TI  - Evaluation of confirmatory strategies for detection of type-specific antibodies
      against herpes simplex virus type 2.
AB  - In this study, the optimal combination of three commercial glycoprotein G-2 (gG
      2)-based herpes simplex virus type 2 (HSV-2) type-specific enzyme-linked
      immunosorbent assays (Euroimmun anti-HSV-2 immunoglobulin G [IgG] ELISA [Eu2],
      Gull HSV-2-specific IgG ELISA [Gu2], and Radim HSV-2 IgG ELISA [Ra2]) and one gG
      2-based HSV-2-specific immunoblot (Euroimmun anti-HSV-1/HSV-2 gG Western blot
      [EuW]) was determined with regard to diagnostic performance and cost efficiency.
      Two hundred fifty serum samples were included in this study, 194 of which were
      from female prostitutes. When a formal primary "gold standard" was defined based
      on majority agreement of the commercial tests, with EuW being decisive in stand
      off situations, the sensitivity and specificity of the assays in the samples from
      prostitutes were as follows: Eu2, 100 and 89.22%; Gu2, 94.44 and 96.08%; Ra2,
      61.18 and 95.10%; and EuW, 98.90 and 100%. The most cost-effective confirmatory
      strategy in the samples from prostitutes was screening with Eu2, retesting
      positive and equivocal samples with Gu2, and resolving the remaining discordant
      results with EuW (estimated additional costs per sample, 79.02%; sensitivity,
      100%; positive predictive value, 96.81%). Applying a self-developed gG-2
      independent assay to the discordant and concordant negative samples in the
      samples from prostitutes suggested that the primary gold standard may have missed
      six HSV-2-positive samples. In conclusion, confirmatory strategies based on
      commercial gG-2-dependent seroassays result in an increase in the specificity of
      HSV-2-specific serology. However, further improvement of the sensitivity of
      current HSV-2-specific serology may require the additional exploitation of the gG
      2-independent type-specific antibody response.

PMID- 11825951
TI  - Typing and subtyping of 83 clinical isolates purified from surgically implanted
      silicone feeding tubes by random amplified polymorphic DNA amplification.
AB  - In this study, 83 clinical isolates purified from biofilms colonizing 18 silicone
      gastrostomy devices (12 "buttons" and six tubes converted to skin level devices)
      were selected for subtype characterization utilizing genetic analysis. The tubes,
      previously used for feeding, remained in place for 3 to 47 months (mean, 20.0
      months) in children ranging in age from 6 months to 17 years. Classification of
      specific microbes using random amplified polymorphic DNA (RAPD) analysis revealed
      genetic similarities and differences among isolates belonging to the same genus.
      Both gram-positive and -negative bacteria were investigated, including 2 isolates
      of Bacillus brevis, 4 isolates of Bacillus licheniformis, 2 isolates of Bacillus
      pumilus, 3 isolates of Enterococcus durans, 19 isolates of Enterococcus faecalis,
      8 isolates of Enterococcus faecium, 2 isolates of Enterococcus hirae, 7 isolates
      of Escherichia coli, 8 isolates of Lactobacillus plantarum, 19 isolates of
      Staphylococcus aureus, 2 isolates of Staphylococcus epidermidis, and 7 isolates
      of Staphylococcus saprophyticus. Amplified DNA fragments (amplicons) provided
      species-specific fingerprints for comparison by agarose gel electrophoresis. A
      total of 62 distinct RAPD types were categorized from the five genera studied.
      Typing analysis suggested cross acquisition of E. coli, E. faecalis, and S.
      aureus in three patient pairs. Genomic polymorphism detection proved efficient
      and reliable for classifying bacterial subtypes isolated from biofilms adhering
      to various portions of commonly employed enteral access tubes.

PMID- 11825952
TI  - Antigenic and genetic characterization of influenza C viruses which caused two
      outbreaks in Yamagata City, Japan, in 1996 and 1998.
AB  - During the 3 years from January 1996 to December 1998, a total of 33 strains of
      influenza C virus were isolated from 10,726 throat swab specimens collected from
      children with acute respiratory illness who visited two pediatric clinics in
      Yamagata City, Japan. These 33 strains were isolated in clusters during two
      different periods, 20 strains in May to August 1996 and the remaining 13 in March
      to June 1998. Antigenic analysis with monoclonal antibodies to the hemagglutinin
      esterase (HE) glycoprotein and phylogenetic analysis of seven RNA segments showed
      that the 33 influenza C viruses isolated were antigenically and genetically
      similar and that they were reassortant viruses which had obtained PB2, PB1, HE,
      M, and NS genes from a C/pig/Beijing/115/81-like virus and P3 and NP genes from a
      C/Mississippi/80-like virus. These observations suggest strongly that during the
      survey period of 3 years, two outbreaks of influenza C occurred in Yamagata City,
      both of which were caused by a reassortant virus having the genome composition
      described above.

PMID- 11825953
TI  - Molecular characterization of methicillin-resistant Staphylococcus epidermidis
      clones: evidence of geographic dissemination.
AB  - Denmark and Iceland are countries where the frequency of methicillin-resistant
      Staphylococcus aureus is very low due to strict infection control and restrictive
      antibiotic use policies. In contrast, methicillin-resistant S. epidermidis (MRSE)
      continues to be isolated as a nosocomial pathogen. The molecular typing by pulsed
      field gel electrophoresis (PFGE) of 136 MRSE isolates from five hospitals in
      Denmark and 94 MRSE isolates from one hospital in Iceland collected in 1997 and
      1998 defined 40 different patterns. Closely related PFGE types were found in
      isolates recovered in Iceland, Denmark, Mexico, Uruguay, Greece, and Cape Verde,
      evidencing for the first time the geographic clonal dissemination of MRSE
      strains. The large majority (87.4%) of the MRSE isolates studied were
      multiresistant.

PMID- 11825955
TI  - Sensitive PCR-restriction fragment length polymorphism assay for detection and
      genotyping of Giardia duodenalis in human feces.
AB  - An assay that uses heminested PCR-restriction fragment length polymorphism
      analysis for the detection and genotyping of Giardia duodenalis on the basis of
      polymorphism in the triose phosphate isomerase (tpi) gene was developed. This
      assay was evaluated with DNA extracted from purified parasite material, bacterial
      cultures, whole human feces containing G. duodenalis and other parasites, and
      their corresponding immunofluorescence-stained fecal smears on glass microscope
      slides. The assay was specific and discriminated between G. duodenalis
      assemblages A and B. RFLP analysis further distinguished two groups (designated
      groups I and II) within assemblage A. Among 35 DNA samples extracted from whole
      feces from patients with confirmed sporadic giardiasis, the tpi gene was
      amplified from 33 (94%). Of these, nine (27%) samples contained assemblage A
      group II, 21 (64%) contained assemblage B, and 3 (9%) contained a mixture of
      assemblage A group II and assemblage B. The tpi gene of G. duodenalis assemblage
      B was amplified from 21 of 24 (88%) DNA samples extracted from whole feces from
      patients with confirmed cases of infection in a nursery outbreak. No
      amplification was detected from the remaining three DNA samples. Overall,
      analysis of DNA extracted from material recovered from stained microscope slides
      identified identical G. duodenalis genotypes in 35 (65%) of the 54 samples for
      which a genotype was established with DNA from whole feces. The heminested PCR
      method developed is sensitive, simple, and rapid to perform and is applicable for
      the analysis of other intestinal pathogens.

PMID- 11825954
TI  - Sensitive enzyme immunoassay for hepatitis B virus core-related antigens and
      their correlation to virus load.
AB  - A sensitive enzyme immunoassay (EIA) specific for hepatitis B virus core antigen
      (HBcAg) and hepatitis B e antigen (HBeAg) was developed. We designated the
      precore/core gene products as hepatitis B virus (HBV) core-related antigens
      (HBcrAg). In order to detect HBcrAg even in anti-HBc/e antibody-positive
      specimens, the specimens were pretreated in detergents. The antibodies are
      inactivated by this pretreatment and, simultaneously, the antigens are released
      and the epitopes are exposed. The assay demonstrated 71 to 112% recovery using
      HBcrAg-positive sera. We observed no interference from the tested anticoagulants
      or blood components. When the cutoff value was tentatively set at 10(3) U/ml, all
      healthy control (HBsAg/HBV-DNA negative; n = 108) and anti-HCV antibody-positive
      (n = 59) sera were identified as negative. The assay showed a detection limit of
      4 x 10(2) U/ml using recombinant antigen. Detection limits were compared in four
      serially diluted HBV high-titer sera. The HBcrAg assay demonstrated higher
      sensitivity than HBV-DNA transcription-mediated amplification (TMA) or HBeAg
      radio immunoassay (RIA) in the dilution test. HBcrAg concentrations correlated
      well with HBV-DNA TMA (r = 0.91, n = 29) and in-house real-time detection-PCR (r
      = 0.93, n = 47) in hepatitis B patients. On HBeAg/anti-HBe antibody
      seroconversion panels, the HBcrAg concentration changed in accordance with HBV
      DNA levels. HBcrAg concentration provides a reflection of HBV virus load
      equivalent to HBV-DNA level, and the assay therefore offers a simple method for
      monitoring hepatitis B patients.

PMID- 11825957
TI  - Tiamulin activity against fastidious and nonfastidious veterinary and human
      bacterial isolates: initial development of in vitro susceptibility test methods.
AB  - Tiamulin is a pleuromutilin derivative used in veterinary practice for the
      control and specific therapy of infections in swine. This report summarizes
      studies to establish standardized susceptibility testing methods, interpretive
      criteria, and reagent details for use in veterinary methods recently developed by
      the National Committee for Clinical Laboratory Standards (NCCLS) (standards M31-A
      and M37-A, NCCLS, Wayne, Pa., 1999). A total of 636 fastidious and nonfastidious
      animal and human pathogens were processed by using media and procedures described
      by the NCCLS. Tiamulin disk diffusion tests used a 30-microg disk concentration,
      and the proposed MIC breakpoints corresponding to levels achievable in animal
      target tissues (lung) were < or =4 microg/ml for susceptibility and > or =32
      microg/ml for resistance. Correlate zone diameters for specific nonfastidious
      species were as follows: for Pasteurella multocida and staphylococci tested on
      Mueller-Hinton agar, susceptibility at > or =19 mm and resistance at < or =11 mm,
      and for Actinobacillus suis, Erysipelothrix rhusiopathiae, and Streptococcus suis
      tested on enriched chocolate Mueller-Hinton agar, susceptibility at > or =16 mm
      and resistance at < or =8 mm. When Actinobacillus pleuropneumoniae was tested, a
      susceptibility breakpoint of < or =16 microg/ml (> or =9 mm) was suggested for
      veterinary fastidious medium broth and enriched chocolate Mueller-Hinton agar.
      Absolute categorical agreement between NCCLS dilution and disk diffusion test
      results with these criteria ranged from 90.5 to 96.2%. Tiamulin susceptibility
      testing methods appear to be accurate in their categorical classification for
      indicated species, and their availability will allow immediate testing of animal
      isolates to guide therapy via appropriate levels of dosing and to monitor the
      development of resistance for agents in this unique class.

PMID- 11825956
TI  - Species-specific serodiagnosis of Lyme arthritis and neuroborreliosis due to
      Borrelia burgdorferi sensu stricto, B. afzelii, and B. garinii by using decorin
      binding protein A.
AB  - The antigenic potential of decorin binding protein A (DbpA) was evaluated in
      serodiagnosis of human Lyme borreliosis (LB). The dbpA was cloned and sequenced
      from the three pathogenic Borrelia species common in Europe. Sequence analysis
      revealed high interspecies heterogeneity. The identity of the predicted amino
      acid sequences was 43 to 62% among Borrelia burgdorferi sensu stricto, B.
      afzelii, and B. garinii. The respective recombinant DbpAs (rDbpAs) were produced
      and tested as antigens by Western blotting and enzyme-linked immunosorbent assay
      (ELISA). One hundred percent of patients with neuroborreliosis (NB) and 93% of
      patients with Lyme arthritis (LA) reacted positively. Sera from the majority of
      patients reacted with one rDbpA only and had no or low cross-reactivity to other
      two variant proteins. In patients with culture-positive erythema migrans (EM),
      the sensitivity of rDbpA immunoglobulin G (IgG) or IgM ELISA was low. The DbpA
      seems to be a sensitive and specific antigen for the serodiagnosis of LA or NB,
      but not of EM, provided that variants from all three pathogenic borrelial species
      are included in the combined set of antigens.

PMID- 11825958
TI  - Experimental infection of domestic cats with Bartonella koehlerae and comparison
      of protein and DNA profiles with those of other Bartonella species infecting
      felines.
AB  - Bartonella koehlerae, a recently described feline Bartonella species, was
      isolated from two naturally infected cats in northern California. We
      experimentally infected domestic cats with B. koehlerae to establish the
      microbiological and immunological characteristics of this infection in cats and
      to compare it to infections with those caused by B. henselae and B. clarridgeiae.
      Four cats were inoculated intradermally with B. koehlerae (8.6 x 10(7) to 3.84 x
      10(8) CFU/ml). None of the cats presented any obvious clinical signs, but all
      cats developed bacteremia, which peaked at 3.36 x 10(4) to 1.44 x 10(6) CFU/ml of
      blood between day 14 and day 36 postinoculation. B. koehlerae-inoculated cats had
      a bacteremia duration (mean, 74 days) shorter than did cats inoculated with B.
      clarridgeiae (mean, 324 days) (P = 0.03). None of the four cats inoculated with
      B. koehlerae had bacteremia relapse. As shown by enzyme-linked immunosorbent
      assay (ELISA) using B. koehlerae outer membrane protein (OMP) antigens, the four
      cats developed a species-specific antibody response, and ELISA testing using
      other feline Bartonella OMP antigens showed statistically lower optical density
      values. All four cats developed similar antibody reactivity patterns to B.
      koehlerae OMP antigens as seen by Western blotting, each with at least 20
      seroreactive protein bands. Using sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis, protein profile differences were observed for both whole-cell
      lysate and OMPs from B. koehlerae, compared with B. henselae and B. clarridgeiae.
      B. koehlerae was more closely related to B. henselae than to B. clarridgeiae by
      protein profile, and this relatedness was also confirmed by analysis of the
      genomic DNA profiles by pulsed-field gel electrophoresis.

PMID- 11825959
TI  - Imported visceral leishmaniasis: diagnostic dilemmas and comparative analysis of
      three assays.
AB  - The present study evaluates the performances of three noninvasive serological
      assays for the detection of immunoglobulin G antibodies to leishmania antigen for
      the diagnosis of imported cases of kala azar (visceral leishmaniasis [VL]) in a
      country, Kuwait, where the disease is not endemic. A total of 323 individuals
      including 21 patients with documented cases of VL, 72 individuals with suspected
      cases of VL, 155 patients with other parasitic infections, and 75 healthy control
      individuals were tested by indirect hemagglutination assay (IHA; Behring
      Diagnostics GmbH, Marburg, Germany), indirect fluorescent-antibody assay (IFA;
      bioMerieux sa, Marcy l'Etoile, France), and a qualitative membrane-based
      immunoassay with recombinant leishmania antigen K39 (strip-test; Intersep Ltd,
      Berkshire, United Kingdom). Our data show that IHA is the most sensitive test
      (100%), followed by IFA (86.6%) and the strip-test (80.0%). The strip-test was
      the most specific (100%) of the three assays, followed by IFA (93.0%) and IHA
      (86.0%). However, the strip-test failed to detect at least three confirmed cases
      of VL. We conclude that IHA is preferred over IFA and the strip-test for the
      screening of individuals with suspected cases of VL, especially in a country
      where VL is not endemic and where the number of cases is regular but limited. The
      details about some of the patients with VL are presented to highlight the
      diversity of clinical presentations and problems encountered in the diagnosis of
      VL in a country where VL is not endemic.

PMID- 11825960
TI  - Diagnosis of human leptospirosis by monoclonal antibody-based antigen detection
      in urine.
AB  - Hybridomas secreting specific monoclonal antibodies (MAb) to all members of the
      genus Leptospira (clone LF9) and those that are specific only to the pathogenic
      species (clones LD5 and LE1) were produced. MAb LF9, which was immunoglobulin G1
      (IgG1), reacted to a 38-kDa component of the sodium dodecyl sulfate
      polyacrylamide gel electrophoresis-separated whole-cell lysates of all Leptospira
      spp., while MAb LD5 and MAb LE1, which were IgG1 and IgG2a, respectively, reacted
      to the 35- to 36-kDa components of all serogroups of the pathogenic species of
      LEPTOSPIRA: The MAb LD5 was used in a dot blot-enzyme-linked immunosorbent assay
      (dot-ELISA) for detecting Leptospira antigen in urine samples serially collected
      from two groups of patients diagnosed with leptospirosis, i.e., 36 clinically
      diagnosed patients and 25 Leptospira culture confirmed patients. Their serum
      samples were tested serologically by IgM Dipstick assay, indirect
      immunofluorescence assay (IFA), and/or microscopic agglutination test (MAT).
      Urine samples of 26 patients diagnosed with other illnesses and 120 healthy
      individuals served as controls. For the first group of patients, who had been ill
      for an average of 3.4 days before hospitalization, the IgM Dipstick test, IFA,
      and MAT were positive for 69.4, 70.0, and 85.7% of patients, while the Leptospira
      antigenuria tested by the MAb-based dot-ELISA was positive for 75.0, 88.9, 97.2,
      97.2, and 100% of patients on days 1, 2, 3, 7, and 14 of hospitalization,
      respectively. All but 1 of 11 patients whose serum samples collected on the first
      day of hospitalization were IgM seronegative, were positive by urine antigen test
      on day 1. This is strong evidence that detection of antigen in urine can provide
      diagnostic information that could be useful in directing early therapeutic
      intervention. The MAT was positive in 10 of 12 patients (83.3%) of the 25 culture
      positive Leptospira patients who had been ill for an average of 5.04 days before
      hospitalization, and the Leptospira antigen was found in 64.0, 84.0, 96.0, 100,
      100, 100, and 100% of the patients' urine samples collected on days 1, 2, 3, 4,
      5, 6, and 7 of hospitalization, respectively. Leptospira antigenuria was found in
      3 of the 26 patients diagnosed with other illnesses and 1 of the 120 healthy
      controls. The reasons for this positivity are discussed. The detection of antigen
      in urine by the monoclonal antibody-based dot-ELISA has high potential for rapid,
      sensitive, and specific diagnosis of leptospirosis at a low cost.

PMID- 11825961
TI  - Development and evaluation of a quantitative, touch-down, real-time PCR assay for
      diagnosing Pneumocystis carinii pneumonia.
AB  - A rapid (time to completion, <4 h, including DNA extraction) and quantitative
      touch-down (QTD) real-time diagnostic Pneumocystis carinii PCR assay with an
      associated internal control was developed, using fluorescence resonance energy
      transfer (FRET) probes for detection. The touch-down procedure significantly
      increased the sensitivity of the assay compared to a non-touch-down procedure.
      Tenfold serial dilutions of a cloned target were used as standards for
      quantification. P. carinii DNA has been detected in respiratory specimens from
      patients with P. carinii pneumonia (PCP) and from patients without clinical
      evidence of PCP. The latter probably represents colonization or subclinical
      infection. It is logical to hypothesize that quantification might prove helpful
      in distinguishing between infected and colonized patients: the latter group would
      have lower copy numbers than PCP patients. A blinded retrospective study of 98
      respiratory samples (49 lower respiratory tract specimens and 49 oral washes),
      from 51 patients with 24 episodes of PCP and 34 episodes of other respiratory
      disease, was conducted. PCR-positive samples from colonized patients contained a
      lower concentration of P. carinii DNA than samples from PCP patients: lower
      respiratory tract samples from PCP and non-PCP patients contained a median of 938
      (range, 2.4 to 1,040,000) and 2.6 (range, 0.3 to 248) (P < 0.0004) copies per
      tube, respectively. Oral washes from PCP and non-PCP patients contained a median
      of 49 (range, 2.1 to 2,595) and 6.5 (range, 2.2 to 10) (P < 0.03) copies per
      tube, respectively. These data suggest that this QTD PCR assay can be used to
      determine if P. carinii is present in respiratory samples and to distinguish
      between colonization and infection.

PMID- 11825962
TI  - Comparative evaluation of the VERSANT HCV RNA 3.0, QUANTIPLEX HCV RNA 2.0, and
      COBAS AMPLICOR HCV MONITOR version 2.0 Assays for quantification of hepatitis C
      virus RNA in serum.
AB  - A comparison of quantitative results expressed in hepatitis C virus (HCV)
      international units per milliliter, obtained from the VERSANT HCV RNA 3.0 (bDNA
      3.0) assay, the QUANTIPLEX HCV RNA 2.0 (bDNA-2.0) assay, and the COBAS AMPLICOR
      HCV MONITOR version 2.0 (HCM-2.0) test was performed. A total of 168 patient
      specimens submitted to the Mayo Clinic Molecular Microbiology Laboratory for HCV
      quantification or HCV genotyping were studied. Of the specimens tested, 97, 88,
      and 79% yielded quantitative results within the dynamic range of the bDNA-3.0,
      bDNA-2.0, and HCM-2.0 assays, respectively. Overall, there was substantial
      agreement between the results generated by all three assays. A total of 15 out of
      29 (52%) of the specimens determined to contain viral loads of <31,746 IU/ml by
      the bDNA-3.0 assay were categorized as containing viral loads within the range of
      31,746 to 500,000 IU/ml by the bDNA-2.0 assay. Although substantial agreement was
      noted between the results generated by the bDNA-2.0 and bDNA-3.0 assays, a bias
      toward higher viral titer by the bDNA-2.0 assay was noted (P = 0.001). Likewise,
      although substantial agreement was noted between the results generated by the HCM
      2.0 and bDNA-3.0 assays, a bias toward higher viral titer by the bDNA-3.0 assay
      was noted (P < or = 0.001). The discrepancy between the HCM-2.0 and bDNA-3.0
      results was more pronounced when viral loads were >500,000 IU/ml and resulted in
      statistically significant differences (P < or = 0.001) in determining whether
      viral loads were above or below 800,000 IU/ml of HCV RNA, the proposed threshold
      value for tailoring the duration of combination therapy. The expression of
      quantitative values in HCV international units per milliliter was a strength of
      both the bDNA-3.0 and HCM-2.0 assays.

PMID- 11825963
TI  - Rapid detection of pyrazinamide-resistant Mycobacterium tuberculosis by a PCR
      based in vitro system.
AB  - Pyrazinamide (PZA), an analog of nicotinamide, is a prodrug for tuberculosis
      which requires conversion to the bactericidal compound pyrazinoic acid by
      bacterial pyrazinamidase activity. Mutations leading to a loss of pyrazinamidase
      activity cause PZA resistance in Mycobacterium tuberculosis. Thus, the detection
      of pyrazinamidase activity makes the discrimination of PZA-resistant tuberculosis
      possible. However, the detection of the pyrazinamidase activity of M.
      tuberculosis isolates needs a large amount of bacilli and is therefore time
      consuming. In this paper, we describe a new method for the detection of
      pyrazinamidase activity with a PCR-based system. The genes encoding
      pyrazinamidase (pncA genes) in 30 resistant clinical isolates were amplified by
      PCR by using forward primers containing bacteriophage T7 promoter sequences at
      their 5" ends. Then the PCR products were directly subjected to an in vitro
      transcription-translation coupled system. All of the PZA-resistant isolates
      tested showed reduced pyrazinamidase activity compared to susceptible M.
      tuberculosis type strain H37Rv. In contrast, all of the 15 susceptible clinical
      isolates exhibited pyrazinamidase activities similar to that of H37Rv. This fact
      suggested the possibility of the usefulness of this system for the rapid
      detection of PZA-resistant M. tuberculosis.

PMID- 11825964
TI  - Improving sensitivity of direct microscopy for detection of acid-fast bacilli in
      sputum: use of chitin in mucus digestion.
AB  - In order to try to improve the results of direct smear microscopy, we used the
      mucus-digesting quality of chitin in tuberculosis (TB) laboratories. For this
      purpose, a total of 430 sputum specimens were processed by the N-acetyl-L
      cysteine concentration, sodium hypochlorite (NaOCl) liquefaction, chitin
      sedimentation, and direct microscopy methods. Then, the smear sensitivity for
      acid-fast bacillus detection by chitin-treated sputum was compared with the
      sensitivity of smears prepared by other methods. Our results showed that the
      chitin solution took less time to completely homogenize the mucoid sputum than
      did the N-acetyl-L-cysteine and NaOCl methods. The N-acetyl-L-cysteine
      concentration method demonstrated sensitivity and specificity levels of 83 and
      97%, respectively. In comparison, the sensitivity of chitin sedimentation was
      80%, with a specificity of 96.7%. The NaOCl liquefaction method showed a
      sensitivity of 78%, with a specificity of 96%. Finally, the sensitivity of direct
      microscopy was lower than those of the other tested methods and was only 46%,
      with a specificity of 90%. The chitin and NaOCl liquefaction methods are both
      easy to perform, and they do not require additional equipment (centrifuges).
      Also, our results demonstrated that the chitin method is less time-consuming than
      the NaOCl method, since only 30 min of incubation is required to bring complete
      sedimentation of bacilli in chitin-treated sputum whereas the NaOCl method needs
      10 to 12 h to give the same results in the same sputum specimens. Therefore, the
      chitin liquefaction and sedimentation method may provide better results in TB
      laboratories of developing countries than the N-acetyl-L-cysteine concentration,
      NaOCl overnight sedimentation, and direct smear microscopy methods.

PMID- 11825965
TI  - Multiserotype enzyme-linked immunosorbent assay as a diagnostic aid for
      periodontitis in large-scale studies.
AB  - Periodontitis is a common chronic oral infection caused by gram-negative
      bacteria, including Actinobacillus actinomycetemcomitans and Porphyromonas
      gingivalis. Periodontitis evokes inflammatory host response locally in the
      periodontium but also systemically. The systemic humoral antibody response
      against oral pathogens can conveniently be measured by an immunoassay. The aim of
      the study was to measure serum immunoglobulin G class antibodies against A.
      actinomycetemcomitans and P. gingivalis by an enzyme-linked immunosorbent assay
      (ELISA) in which mixtures of several serotypes of the pathogens were used as
      antigens to avoid biasing of the results in favor of a particular strain. For A.
      actinomycetemcomitans the antigen consisted of six strains representing serotypes
      a, b, c, d, and e and one nonserotypeable strain. In the P. gingivalis ELISA,
      antigens representing serotypes a, b, and c were used. Serum samples from 90
      subjects, including 35 samples from patients with diagnosed periodontitis, 10
      samples from periodontally healthy controls, and 45 samples from randomly
      selected apparently healthy volunteers (referred to as "healthy subjects"), were
      tested. For both pathogens the antibody levels (means +/- standard deviations) of
      the patients--xpressed as area under the dilution curve--were significantly
      higher than those for healthy controls or healthy subjects, with values for A.
      actinomycetemcomitans and P. gingivalis, respectively, as follows: patients,
      22.60 +/- 9.94 mm(2) and 26.72 +/- 11.13 mm(2); healthy controls, 9.99 +/- 3.92
      mm(2) and 6.90 +/- 3.38 mm(2); and healthy subjects, 16.85 +/- 6.67 mm(2) and
      8.51 +/- 4.23 mm(2). The serotype mixture ELISA is suitable for measuring
      antibodies against periodontal pathogens in large epidemiological studies in
      order to evaluate the role of periodontitis as a risk factor for other diseases.

PMID- 11825966
TI  - Quantification of feline herpesvirus 1 DNA in ocular fluid samples of clinically
      diseased cats by real-time TaqMan PCR.
AB  - A fluorogenic PCR was established for the quantification of feline herpesvirus 1
      (FeHV-1) DNA in ocular fluid samples of clinically diseased cats. The new assay
      was specific for FeHV-1 and sensitive. The 100% detection rate ranged from 0.6 to
      6 50% tissue culture infective doses per sample. When spiked samples with known
      quantities of virus were used, infectious virus titers and quantification of
      viral DNA by PCR correlated to each other in a linear fashion (R(2) = 0.9858)
      over a range of 4 orders of magnitude. Within this range, it was possible to
      calculate the FeHV-1 DNA content from a given infectious dose, and vice versa.
      The new diagnostic procedure was applied to ocular fluid samples from cats
      experimentally infected with FeHV-1 and specific FeHV-1-free cats. A good
      correlation between virus titer and quantitative PCR was observed, although only
      early in infection. In a second stage, the titer of infectious virus collapsed,
      while the PCR signal remained high. A constantly decreasing PCR signal
      accompanied by negative virus isolation was characteristic for a final stage of
      the infection. Finally, clinical samples from 20 cats that were suspected to
      suffer from FeHV-1 infection were analyzed. By comparing virus titers and
      quantitative PCR signals, it was possible to determine the current stage of the
      ongoing infection. Based on these findings, comparison of the results of
      consecutive samples allows the tracking of the course of the infection.
      Therefore, the new method combines the advantages of the two previously
      established conventional methods, qualitative PCR and virus isolation and
      titration.

PMID- 11825967
TI  - Application of restriction fragment length polymorphism analysis of VP7-encoding
      genes: fine comparison of Irish and global rotavirus isolates.
AB  - A restriction fragment length polymorphism (RFLP) detection assay was developed
      to examine the genetic relationship(s) among VP7-encoding genes from 100 Irish
      rotavirus isolates and 30 randomly selected global rotavirus isolates (from the
      current databases). RFLP analysis of the VP7 gene segments was performed
      independently with three enzymes (RsaI, AluI, and EcoRV) in separate reactions by
      direct digestion of the DNA product amplified by reverse transcriptase (RT)
      mediated PCR (RT-PCR) or by using computational methods. Thirty-six RFLP patterns
      were identified for all 130 strains, and of these, only nine patterns were
      associated with the Irish isolates. A correlation between the G type of the Irish
      isolates and certain single or combined enzyme profiles was apparent. These data
      suggested that the Irish wild-type rotavirus population was homogeneous and could
      be distinguished by RFLP analysis from global isolates of the same serotype(s).
      The deduced amino acid sequences of the VP7 RT-PCR products from six Irish
      isolates known to be of the G serotype revealed significant amino acid
      substitutions within major antigenic regions. In addition, these data identified
      the existence of at least two genetic lineages within serotype G1 strains which
      were distinguishable by RFLP analysis.

PMID- 11825968
TI  - Epidemiology of tuberculosis in Hamburg, Germany: long-term population-based
      analysis applying classical and molecular epidemiological techniques.
AB  - To determine a detailed picture of tuberculosis (TB) epidemiology in Hamburg,
      Germany, 423 Mycobacterium tuberculosis complex isolates from 77.0% of all
      patients with culture-confirmed TB diagnosed from 1997 to 1999 in Hamburg were
      analyzed by IS6110 DNA fingerprinting. IS6110 restriction fragment length
      polymorphism (RFLP) clusters were assumed to have arisen from recent
      transmission. Results of contact tracing and additional patient interviews were
      used for further epidemiological analyses. Of the 423 cases, 398 were included in
      the cluster analysis, of which 135 (33.9%) were classified into 35 clusters
      ranging from 2 to 23 patients. Epidemiological links verifying recent
      transmission could be confirmed for 87 of the 135 clustered patients. Risk
      factors for recent transmission were calculated by a two-step procedure: first,
      based on patients with clustered isolates; and second, based on patients with
      clustered isolates and transmission links. In both analyses, alcohol abuse
      appeared to be the strongest predictor for recent transmission, followed by a
      history of previous contact tracing and unemployment. Homelessness, foreign
      ethnicity, sex, drug addiction, and human immunodeficiency virus positivity were
      not independent risk factors for clustering in multivariate analyses. Classical
      contact tracing performed prior to IS6110 RFLP analysis identified only 24 of the
      135 clustered patient. In conclusion, recent transmission seems to be frequent in
      Hamburg and was found to be strongly associated with alcohol abuse. Conventional
      contact tracing appears to be insufficient for the detection of recent
      transmission chains. The data presented also indicate that improved TB control
      strategies, including the use of RFLP for the detection of transmission chains,
      are needed for TB control in the setting of countries with a low incidence of TB.

PMID- 11825969
TI  - Detection of Ehrlichia canis in canine carrier blood and in individual
      experimentally infected ticks with a p30-based PCR assay.
AB  - Detection of vector-borne pathogens is necessary for investigation of their
      association with vertebrate and invertebrate hosts. The ability to detect
      Ehrlichia spp. within individual experimentally infected ticks would be valuable
      for studies to evaluate the relative competence of different vector species and
      transmission scenarios. The purpose of this study was to develop a sensitive PCR
      assay based on oligonucleotide sequences from the unique Ehrlichia canis gene,
      p30, to facilitate studies that require monitoring this pathogen in canine and
      tick hosts during experimental transmission. Homologous sequences for Ehrlichia
      chaffeensis p28 were compared to sequences of primers derived from a sequence
      conserved among E. canis isolates. Criteria for primer selection included
      annealing scores, identity of the primers to homologous E. chaffeensis sequences,
      and the availability of similarly optimal primers that were nested within the
      target template sequence. The p30-based assay was at least 100-fold more
      sensitive than a previously reported nested 16S ribosomal DNA (rDNA)-based assay
      and did not amplify the 200-bp target amplicon from E. chaffeensis, the human
      granulocytic ehrlichiosis agent, or Ehrlichia muris DNA. The assay was used to
      detect E. canis in canine carrier blood and in experimentally infected
      Rhipicephalus sanguineus ticks. Optimized procedures for preparing tissues from
      these hosts for PCR assay are described. Our results indicated that this p30
      based PCR assay will be useful for experimental investigations, that it has
      potential as a routine test, and that this approach to PCR assay design may be
      applicable to other pathogens that occur at low levels in affected hosts.

PMID- 11825971
TI  - Rapid and inexpensive drug susceptibility testing of Mycobacterium tuberculosis
      with a nitrate reductase assay.
AB  - Multidrug-resistant tuberculosis is an increasing public health concern in many
      parts of the world, especially in low-income countries, where most cases occur.
      Traditional drug susceptibility testing is either time-consuming, such as the
      proportion method on solid media, or expensive, such as the BACTEC 460 system. We
      have evaluated a new nitrate reductase assay (NRA) that depends on the ability of
      Mycobacterium tuberculosis to reduce nitrate to nitrite. The reduction can be
      detected using specific reagents, which produce a color change. We tested a panel
      of 57 M. tuberculosis strains with various resistance patterns. The bacteria were
      inoculated on Lowenstein-Jensen medium, either without drugs or with rifampin,
      isoniazid, streptomycin, or ethambutol and with potassium nitrate (KNO(3))
      incorporated. After incubation for 7, 10, or 14 days, the reagents were added and
      nitrate reduction, indicating growth, could be detected by a color change.
      Sensitivities to and specificities for drugs as determined by the NRA method
      compared to those determined by the BACTEC 460 method were 100 and 100% for
      rifampin, 97 and 96% for isoniazid, 95 and 83% for streptomycin, and 75 and 98%
      for ethambutol, respectively. The results were in the majority of the cases
      available in 7 days. The evaluated method is rapid and inexpensive and could
      correctly identify most resistant and sensitive M. tuberculosis strains. It has
      the potential to become an interesting alternative to existing methods, such as
      the proportion and BACTEC methods, particularly in resource-poor settings.

PMID- 11825970
TI  - Novel antigens of Helicobacter pylori correspond to ulcer-related antibody
      pattern of sera from infected patients.
AB  - Recently, we reported that the patterns of antibodies to Helicobacter pylori
      protein antigens in serum may be useful for screening patients at high risk for
      ulcers (P. Aucher et al., J. Clin. Microbiol. 36:931-936, 1998). Here we report
      the identification, by a combination of electrophoretic, immunochemical, and
      protein sequencing methods, of five antigens that correspond to this antibody
      pattern: groEL, catalase A, flagellin A, beta-ketoacyl-acyl carrier protein
      synthase I (beta-ketoacyl-ACP S), and peptidyl prolyl cis-trans isomerase
      (PPiase). Beta-Ketoacyl-ACP S and PPiase are reported for the first time as
      antigens of diagnostic interest in infections by H. pylori. The antigenicity of
      the five antigens, together with those of CagA and VacA, was tested in an
      immunoblot assay with water-soluble protein extracts from two H. pylori
      pathogenic strains (HP 141 and ATCC 43579) and panels of sera from H. pylori
      positive patients with gastroduodenal ulcers (GDU), nonulcer dyspepsia (NUD), as
      well as sera from H. pylori-negative healthy volunteers. For catalase A, groEL,
      and flagellin A antigens, no overall statistically important values were found
      making it possible to discriminate between patients with GDU and NUD. For both H.
      pylori strains, the mean performance indices (MPI) presenting percentages of
      correctly classified patients with GDU and NUD showed that the most significant
      antibody patterns were as follows: anti-VacA + anti-beta-ketoacyl-ACP S (MPI =
      76.1), anti-VacA + anti-PPiase (MPI = 71.8), and anti-CagA + anti-VacA + anti
      beta-ketoacyl-ACP S (MPI = 70.5). Antibody patterns detected with these antigen
      profiles may therefore be useful in developing a diagnostic test designed to
      predict the clinical severity of the H. pylori infection within the adult
      population of France.

PMID- 11825973
TI  - Development and evaluation of real-time PCR-based fluorescence assays for
      detection of Chlamydia pneumoniae.
AB  - Chlamydia pneumoniae is an important respiratory pathogen recently associated
      with atherosclerosis and several other chronic diseases. Detection of C.
      pneumoniae is inconsistent, and standardized PCR assays are needed. Two real-time
      PCR assays specific for C. pneumoniae were developed by using the fluorescent dye
      labeled TaqMan probe-based system. Oligonucleotide primers and probes were
      designed to target two variable domains of the ompA gene, VD2 and VD4. The limit
      of detection for each of the two PCR assays was 0.001 inclusion-forming unit.
      Thirty-nine C. pneumoniae isolates obtained from widely distributed geographical
      areas were amplified by the VD2 and VD4 assays, producing the expected 108- and
      125-bp amplification products, respectively. None of the C. trachomatis serovars,
      C. psittaci strains, other organisms, or human DNAs tested were amplified. The
      amplification results of the newly developed assays were compared to the results
      of culturing and two nested PCR assays, targeting the 16S rRNA and ompA genes.
      The assays were compared by testing C. pneumoniae purified elementary bodies,
      animal tissues, 228 peripheral blood mononuclear cell (PBMC) specimens, and 179
      oropharyngeal (OP) swab specimens obtained from ischemic stroke patients or
      matched controls. The real-time VD4 assay and one nested PCR each detected C.
      pneumoniae in a single, but different, PBMC specimen. Eleven of 179 OP specimens
      (6.1%) showed evidence of the presence of C. pneumoniae in one or more tests. The
      real-time VD4 assay detected the most positive results of the five assays. We
      believe that this real-time PCR assay offers advantages over nested PCR assays
      and may improve the detection of C. pneumoniae in clinical specimens.

PMID- 11825972
TI  - Identification of four distinct genotypes of Candida dubliniensis and detection
      of microevolution in vitro and in vivo.
AB  - The present study investigates further the population structure of Candida
      dubliniensis and its ability to exhibit microevolution. Using 98 isolates
      (including 80 oral isolates) from 94 patients in 15 countries, we confirmed the
      existence of two distinct populations within the species C. dubliniensis,
      designated Cd25 group I and Cd25 group II, respectively, on the basis of DNA
      fingerprints generated with the C. dubliniensis-specific probe Cd25. The majority
      of Cd25 group I isolates (48 of 71, 67.6%) were from human immunodeficiency virus
      (HIV)-infected individuals, whereas the majority of Cd25 group II isolates (19 of
      27, 70.4%) were from HIV-negative individuals (P < or = 0.001). Nucleotide
      sequence analysis of the internal transcribed spacer (ITS) regions of the rRNA
      genes from 19 representative isolates revealed the presence of four separate
      genotypes. All of the Cd25 group I isolates tested belonged to genotype 1, while
      the Cd25 group II population was comprised of three distinct genotypes (genotypes
      2 to 4), which corresponded to distinct clades within the Cd25 group II
      population. These findings were confirmed using genotype-specific PCR primers
      with 70 isolates. We also showed that C. dubliniensis can exhibit microevolution
      in vivo and in vitro as occurs in other yeast species. DNA fingerprinting using
      the C. dubliniensis probes Cd25, Cd24, and Cd1 and karyotype analysis of multiple
      oral isolates recovered from the same specimen from each of eight separate
      patients revealed microevolution in six of eight of the clonal populations.
      Similarly, sequential clonal isolates from various anatomical sites in two
      separate patients exhibited microevolution. Microevolution was also shown to
      occur when two clinical isolates susceptible to fluconazole were exposed to the
      drug in vitro. The epidemiological significance of the four C. dubliniensis
      genotypes and the ability of C. dubliniensis to undergo microevolution has yet to
      be established.

PMID- 11825974
TI  - Comparison of three commercially available peptide-based immunoglobulin G (IgG)
      and IgA assays to microimmunofluorescence assay for detection of Chlamydia
      trachomatis antibodies.
AB  - Three commercially available, peptide-based enzyme-linked immunosorbent assay
      (ELISA) systems (Chlamydia trachomatis IgG and IgA EIA [CT-EIA; Labsystems OY,
      Helsinki, Finland], SeroCT IgG and IgA [SeroCT; Savyon Diagnostics Ltd., Ashdod,
      Israel], and Chlamydia trachomatis IgG and IgA pELISA [CT pELISA; Medac, Wedel,
      Germany]) were evaluated for the detection of serum immunoglobulin G (IgG) and
      IgA antibodies specific for Chlamydia trachomatis and compared to the "gold
      standard" assay, the microimmunofluorescence (MIF) assay. Serological responses
      were analyzed in 149 women aged 20 to 30 years. Cervical swabs obtained from
      these women were examined for C. trachomatis by PCR, and 43 were found to be
      positive. The overall seroprevalence rates detected by CT-EIA, SeroCT, CT pELISA,
      and the MIF assay were 42, 42, 35, and 39%, respectively, for IgG and 7, 7, 3,
      and 7%, respectively, for IgA. The IgG seroprevalence rates for the PCR-positive
      women were two to three times higher than those for the PCR-negative women, i.e.,
      72 versus 29%, 72 versus 29%, 47 versus 26%, and 74 versus 25% for CT-EIA,
      SeroCT, CT pELISA, and the MIF assay, respectively. After discrepancy analysis,
      the sensitivity, specificity, positive predictive value, and negative predictive
      value were calculated for the IgG assays; for CT-EIA they were 84.7, 98.6, 98.4,
      and 86.7%, respectively; for CT pELISA they were 71.4, 97.3, 96.2, and 78.3%,
      respectively; for SeroCT they were 84.7, 98.6, 98.4, and 86.3%, respectively; and
      for the MIF assay they were 79.2, 83.1, 98.3, and 83.1%, respectively. In
      conclusion, these peptide-based ELISA systems for the serological detection of C.
      trachomatis infection performed as well as the MIF assay. Since these tests are
      less time-consuming, less expensive, and easier to perform than the MIF assay,
      they might be useful in the serodiagnosis of chlamydial infection.

PMID- 11825975
TI  - Typing of Pasteurella multocida isolated from pigs with and without porcine
      dermatitis and nephropathy syndrome.
AB  - Porcine dermatitis and nephropathy syndrome (PDNS) is a sporadic, usually fatal
      disease of growing and finishing pigs that has been recognized in many pig
      producing countries. Pasteurella multocida strains isolated from 15 pigs with
      PDNS and 51 pigs without PDNS were characterized by capsule and somatic antigen
      typing, random amplified polymorphic DNA (RAP-D) typing, and restriction analysis
      of genomic DNA using pulsed-field gel electrophoresis (PFGE). While capsular,
      somatic, and RAP-D typing did not discriminate PDNS isolates from non-PDNS
      isolates, all of the isolates from PDNS cases showed an identical ApaI PFGE
      restriction pattern. This pattern was also found in a high proportion (36%) of P.
      multocida strains isolated from non-PDNS cases. Isolation of a single variant of
      P. multocida from tissues of pigs with PDNS warrants further investigation into
      the possible role of these bacteria in the etiology of the disease.

PMID- 11825976
TI  - Rapid identification of Candida species by confocal Raman microspectroscopy.
AB  - Candida species are important nosocomial pathogens associated with high mortality
      rates. Rapid detection and identification of Candida species can guide a
      clinician at an early stage to prescribe antifungal drugs or to adjust empirical
      therapy when resistant species are isolated. Confocal Raman microspectroscopy is
      highly suitable for the rapid identification of Candida species, since Raman
      spectra can be directly obtained from microcolonies on a solid culture medium
      after only 6 h of culturing. In this study, we have used a set of 42 Candida
      strains comprising five species that are frequently encountered in clinical
      microbiology to test the feasibility of the technique for the rapid
      identification of Candida species. The procedure was started either from a
      culture on Sabouraud medium or from a positive vial of an automated blood culture
      system. Prior to Raman measurements, strains were subcultured on Sabouraud medium
      for 6 h to form microcolonies. Using multivariate statistical analyses, a high
      prediction accuracy (97 to 100%) was obtained with the Raman method.
      Identification with Raman microspectroscopy may therefore be significantly faster
      than identification with commercial identification systems that allow various
      species to be identified and that often require 24 to 48 h before a reliable
      identification is obtained. We conclude that confocal Raman microspectroscopy
      offers a rapid, accurate, and easy-to-use alternative for the identification of
      clinically relevant Candida species.

PMID- 11825978
TI  - Evaluation of automated BACTEC MGIT 960 system for testing susceptibility of
      Mycobacterium tuberculosis to four major antituberculous drugs: comparison with
      the radiometric BACTEC 460TB method and the agar plate method of proportion.
AB  - We evaluated the performance of BACTEC MGIT 960 for automated testing of the
      susceptibility of 133 strains of Mycobacterium tuberculosis to streptomycin,
      isoniazid, rifampin, and ethambutol. The BACTEC MGIT 960 results were compared
      with those obtained with the radiometric BACTEC 460TB system, and when there was
      disagreement, the method of proportion on agar plates was used as a reference
      method. Strains resistant to the critical concentration of streptomycin,
      isoniazid, or ethambutol were also tested with a second, higher concentration.
      The overall agreement between the two systems was 96.7%, and the 18 discrepancies
      were resolved in favor of BACTEC 460TB in 11 cases and in favor of BACTEC MGIT
      960 in 7, a difference which was not statistically significant. Apart from the
      assay's low specificity for ethambutol, which was low for the radiometric assay
      as well, good sensitivity and specificity values characterized BACTEC MGIT 960.
      The average time required for completion of the test was 2.5 days shorter with
      BACTEC 460TB. In conclusion, BACTEC MGIT 960 appears to be a suitable replacement
      for the radiometric method of antimicrobial susceptibility testing of M.
      tuberculosis. The problem of frequent contamination of BACTEC MGIT 960 tests
      needs to be quickly resolved; in fact, 14 strains had to be reprocessed because
      of contamination.

PMID- 11825977
TI  - PCR-based diagnosis of acute and chronic cutaneous leishmaniasis caused by
      Leishmania (Viannia).
AB  - We evaluated PCR methods for diagnosis of acute and chronic cutaneous
      leishmaniasis (CL) in an area of Colombia where Leishmania (Viannia) is endemic.
      The PCR method specifically amplified whole linearized minicircle kinetoplast DNA
      (kDNA) of the Leishmania subgenus Viannia from biopsy lysates. PCR products were
      detected in agarose gels. For 255 acute cases, this PCR method had greater
      sensitivity (75.7%) than each conventional method, i.e., microscopic examination
      of Giemsa-stained lesion scraping (46.7%), biopsy culture (55.3%), aspirate
      culture (46.3%), and the conventional methods combined (70.2%). Among 44 cases of
      chronic CL, amplification of biopsy DNA was more sensitive (45.5%) than the
      individual (4.5 to 27.7%) and combined (27.3%) conventional methods. The
      detection of kDNA in biopsies from chronic lesions was enhanced by a
      chemiluminescent dot blot hybridization, which produced a sensitivity of 65.8%
      when alone and 90.9% when in combination with DNA extraction of biopsy lysates (P
      < 0.001). Three biopsies from 84 skin lesions of other etiologies were falsely
      positive by PCR (specificity, 96.4%). PCR detected kDNA more frequently in
      biopsies (detection level, 83.9%) than in aspirates (74.7%) from 103 cases of
      acute CL. Among aspirates from 53 chronic cases of CL, the alternative methods,
      DNA extraction and hybridization, increased sensitivity from 41.5 to 56.6% (P >
      0.05). This enhanced PCR method in chronic biopsies was so much more sensitive
      than conventional methods that it should be considered the preferred diagnostic
      method for chronic CL. These findings support the appropriate incorporation of
      PCR into diagnostic strategies for cutaneous leishmaniasis.

PMID- 11825979
TI  - Molecular characterization of extended-spectrum beta-lactamases produced by
      nosocomial isolates of Enterobacteriaceae from an Italian nationwide survey.
AB  - Extended-spectrum beta-lactamases (ESBLs) are widespread in hospital settings
      worldwide. The present investigation was undertaken to assess the distribution
      and prevalence of ESBLs belonging to the TEM and SHV families in 448 ESBL
      producing clinical isolates of Enterobacteriaceae collected from 10 different
      Italian hospitals. The natures of TEM and SHV determinants were identified by
      direct sequencing of PCR-amplified genes. TEM-52 and SHV-12 were the most common
      variants, and they were found in most hospitals and in several different species.
      Other less frequent variants included TEM-5, TEM-12, TEM-15, TEM-19, TEM-20, TEM
      24, TEM-26, TEM-43, TEM-60, TEM-72, TEM-87, SHV-2a, SHV-5, and SHV-11. Proteus
      mirabilis was the most common producer of TEM-type ESBLs, while Klebsiella
      pneumoniae was the most common producer of SHV-type ESBLs. The distribution of
      TEM- and SHV-type ESBL variants in Enterobacteriaceae from Italian hospitals
      exhibited notable differences from those from other geographical settings.

PMID- 11825980
TI  - Genetic diversity of Streptococcus suis strains isolated from pigs and humans as
      revealed by pulsed-field gel electrophoresis.
AB  - The genetic diversity of 123 Streptococcus suis strains of capsular types 2, 1/2,
      3, 7, and 9, isolated from pigs in France and from humans in different countries,
      was evaluated by pulsed-field gel electrophoresis (PFGE) of DNA restricted with
      SmaI. The method was highly discriminative (D = 0.98), results were reproducible,
      and the PFGE analysis was easy to interpret. Among all S. suis strains, 74 PFGE
      patterns were shown. At 60% homology, three groups (A, B, and C) were identified,
      and at 69% homology, eight subgroups (a to h) were observed. Strains isolated
      from diseased pigs or from humans were statistically clustered in group B,
      especially in subgroup d. By contrast, S. suis strains isolated from clinically
      healthy pigs were preferentially included in subgroup b of group A. Relationships
      could be established between capsular types 1/2, 3, and 9 and groups A, e, and B,
      respectively. S. suis strains isolated from humans were homogeneous, and a very
      high level of association between these strains and four DNA patterns was
      observed. The PFGE used in this study is a very useful tool for evaluating the
      genetic diversity of S. suis strains, and it would be used for epidemiological
      investigations.

PMID- 11825981
TI  - Molecular profiles of group B streptococcal surface protein antigen genes:
      relationship to molecular serotypes.
AB  - The study of surface protein antigens of group B streptococci (GBS) is important
      for understanding of the pathogenesis and epidemiology of infection, and several
      of these antigens have been proposed as components of GBS conjugate vaccines. In
      a previous study, we developed a novel PCR-and-sequencing system for
      identification of GBS serotypes and serosubtypes based on the capsular
      polysaccharide synthesis (cps) gene cluster. In this study, we used published
      sequences to develop PCR assays for identification of genes encoding GBS surface
      proteins including C alpha (bca), C alpha-like proteins 2 and 3 (alp2 and alp3),
      Rib (rib), and C beta (bac). We showed that the prototype R reference strain,
      Prague 25/60, contained a novel alpha-like protein antigen gene (the proposed
      alp4), which presumably encodes an atypical, but antigenically similar, R-like
      protein. Initial evaluation of these gene-specific assays showed excellent
      specificity. By combining cps serotypes, serosubtypes, and surface protein gene
      profiles, we were able to divide 224 GBS isolates into 31 serovariants. GBS bac
      positive strains could be further subtyped into 11 groups and 20 subgroups. Our
      results confirmed and extended reported associations between some cps serotypes
      and serosubtypes, on the one hand, and surface protein genes, on the other:
      serosubtypes III-1 and III-2 were associated with rib, serosubtype III-3 with
      alp2, serotype Ib with bca and bac, and serotype V with alp3. The associations
      between serotype Ia and bca, bca repetitive unit, and bca repetitive unit-like
      sequence-containing genes need to be studied further. These PCR-based methods
      will provide an alternative and objective tool for subtyping of GBS based on
      surface protein antigen genes.

PMID- 11825982
TI  - Predominance of Trypanosoma cruzi lineage I in Mexico.
AB  - Randomly amplified polymorphic DNA (RAPD) has emerged as an effective genetic
      marker for analysis of Trypanosoma cruzi population variability. This method has
      been used to study the genetic variability of Mexican T. cruzi stocks and to
      relate these results to previous classifications. High clonal diversity was
      observed among the Mexican populations: 24 RAPD types were scored among 56 stocks
      analyzed. Only two stocks (3.6%) belonged to the T. cruzi II lineage, while all
      others belonged to T. cruzi I. The robustness of these clusters was statistically
      highly significant. Mexican T. cruzi I stocks formed a homogeneous group with
      reduced genetic distances among its members. Parasites from this group were
      isolated from both domestic and sylvatic cycles over a broad geographic area in
      Mexico. The two Mexican stocks classified as T. cruzi II (isolated from sylvatic
      cycles) were of the same RAPD type, although they were not closely related to the
      three reference T. cruzi II stocks circulating in domestic cycles in Argentina,
      Brazil, Bolivia, and Chile. These stocks were also unrelated to the formerly
      named Zymodeme III.

PMID- 11825983
TI  - Selective amplification of tyv (rfbE), prt (rfbS), viaB, and fliC genes by
      multiplex PCR for identification of Salmonella enterica serovars Typhi and
      Paratyphi A.
AB  - The PCR primers for O, H, and Vi antigen genes, tyv (rfbE), prt (rfbS), fliC-d,
      fliC-a, and viaB, were designed and used for the rapid identification of
      Salmonella enterica serovars Typhi and Paratyphi A with multiplex PCR. The
      results showed that all the clinical isolates examined of Salmonella serovars
      Typhi and Paratyphi A were accurately identified by this assay.

PMID- 11825984
TI  - Evaluation of Chlamydia pneumoniae and Mycoplasma pneumoniae as etiologic agents
      of persistent cough in adolescents and adults.
AB  - Chlamydia pneumoniae and Mycoplasma pneumoniae were evaluated as agents of
      persistent cough in adolescents and adults (n = 491). Tests of 473 respiratory
      specimens by culture or PCR or both identified four episodes (0.8%) of M.
      pneumoniae-associated illness and no episodes of C. pneumoniae illness,
      suggesting that these bacteria do not frequently cause persistent cough.

PMID- 11825985
TI  - Comparison of Digene hybrid capture 2 and conventional culture for detection of
      Chlamydia trachomatis and Neisseria gonorrhoeae in cervical specimens.
AB  - Digene's Hybrid Capture 2 (HC2) CT/GC, CT-ID, and GC-ID DNA tests were evaluated
      by comparison to traditional culture methods for detecting Chlamydia trachomatis
      and Neisseria gonorrhoeae infections in 669 cervical specimens from high-risk
      female populations attending two sexually transmitted disease clinics. For
      detection of either or both infections, the HC2 CT/GC test algorithm had 93.8%
      sensitivity and 95.9% specificity compared to those of culture. After resolution
      of discrepant results by direct fluorescent-antibody (DFA) staining or PCR assay,
      the relative sensitivity and specificity of the HC2 CT/GC test algorithm
      increased to 94.8 and 99.8%, while the values for culture were 83.6% (McNemar's P
      value, 0.0062) and 100%, respectively. For detection of the individual pathogens,
      the relative sensitivities for the HC2 CT-ID and GC-ID tests were 97.2 and 92.2%
      and the specificities were greater than 99% compared to culture adjucated by DFA
      staining and PCR. Test performance varied at the two clinics: the HC2 CT/GC
      algorithm, CT-ID, and GC-ID tests had significantly higher sensitivities
      (McNemar's P value, <0.05) than that of culture for the population at one clinic
      as well as for the combined populations. At the other clinic, the HC2 tests
      performed as well as culture.

PMID- 11825986
TI  - Diffusely adherent Escherichia coli as a cause of acute diarrhea in young
      children in Northeast Brazil: a case-control study.
AB  - In a prospective study carried out in two urban centers in northeastern Brazil,
      195 HEp-2-adherent Escherichia coli strains were isolated; 110 were identified as
      the only pathogen in stools of children with diarrhea, and 85 were from controls.
      Enteropathogenic E. coli isolates were identified in 21 children with diarrhea
      (8.9%) and 7 children without diarrhea (3.0%), and they were significantly
      associated with diarrhea (P < 0.01). Enteroaggregative E. coli strains were
      isolated from 40 children with diarrhea (16.9%) and 38 children without diarrhea
      (16.4%) and showed no correlation with diarrhea (P > 0.5). In 49 children with
      diarrhea (20.7%) and 40 children without diarrhea (17.3%), diffusely adherent E.
      coli (DAEC) isolates were detected and were not found to be associated with
      diarrhea (P = 0.41). However, after stratification, for children older than 12
      months of age a significant correlation between DAEC infection and diarrhea was
      detected (P = 0.01). These results suggest that DAEC isolates should be
      considered potential pathogens in northeastern Brazil and also confirm the
      association of DAEC with age-dependent diarrhea.

PMID- 11825987
TI  - Antibiotic resistance of Helicobacter pylori strains in Japanese children.
AB  - The resistance of Helicobacter pylori to the recently available antibiotic
      treatment regimens has been a growing problem. We investigated the prevalence of
      H. pylori resistance to clarithromycin, metronidazole, and amoxicillin among 51
      H. pylori isolates from Japanese children. In addition, the mutations of the
      corresponding gene were studied by PCR and restriction fragment length
      polymorphism analysis. Primary resistance to clarithromycin, metronidazole, and
      amoxicillin was detected in 29, 24, and 0% of strains, respectively. The
      eradication rates in clarithromycin-susceptible and -resistant strains were 89
      and 56%, respectively (P < 0.05). The prevalence of strains with acquired
      resistance to clarithromycin (78%) was higher than that of strains with primary
      resistance (P < 0.01). Among the clarithromycin-resistant strains studied, 92%
      showed cross-resistance to azithromycin. No acquired resistance to amoxicillin
      was demonstrated. The A2144G mutation in the 23S rRNA gene was detected in 11 of
      12 (92%) clarithromycin-resistant strains tested, whereas the mutation was not
      detected in any of the 15 susceptible strains. The deletion of the rdxA gene was
      not demonstrated in any of the strains. The results indicate that a high
      prevalence of clarithromycin-resistant strains is associated with eradication
      failure. Testing of susceptibility to clarithromycin is recommended.

PMID- 11825989
TI  - Discrimination of single-copy IS6110 DNA fingerprints of Mycobacterium
      tuberculosis isolates by high-resolution minisatellite-based typing.
AB  - Seven isoniazid-resistant isolates with mutations in the NADH dehydrogenase (ndh)
      gene were molecularly typed by IS6110-based restriction fragment length
      polymorphism analysis. All seven isolates with the R268H mutation had identical
      1.4-kb IS6110 fingerprints. High-resolution minisatellite-based typing
      discriminated five of these isolates; two isolates were identical.

PMID- 11825990
TI  - Use of pulsed-field gel electrophoresis, enterobacterial repetitive intergenic
      consensus typing, and automated ribotyping to assess genomic variability among
      strains of nontypeable Haemophilus influenzae.
AB  - We compared 75 nontypeable (NT) Haemophilus influenzae isolates by pulsed-field
      gel electrophoresis (PFGE), enterobacterial repetitive intergenic consensus
      (ERIC)-PCR, and automated ribotyping. PFGE was the most discriminatory of the
      techniques. ERIC-PCR provides a useful screen but should not replace other
      techniques as the sole method to group NT H. influenzae strains.

PMID- 11825988
TI  - Frequency of isolation of Staphylococcus lugdunensis in consecutive urine
      cultures and relationship to urinary tract infection.
AB  - Recent reports associate Staphylococcus lugdunensis with severe infection in
      humans. The frequency of this microorganism in urine cultures is unknown. Five
      hundred isolates of coagulase-negative staphylococci (CoNS) were recovered from
      4,652 consecutive urine specimens submitted for culture to the Mayo Clinic
      Microbiology Laboratory. Thirty-one (6%) of 500 isolates of CoNS were identified
      as S. lugdunensis. In no case was S. lugdunensis isolated in pure culture; 29
      (94%) of 31 S. lugdunensis isolates were part of mixed nonpathogenic flora.
      Medical records were reviewed for 30 of the 31 patients from whom these 31
      isolates were isolated. Twenty-one (70%) of the 30 evaluable patients were not
      treated with antibiotics; the remaining 9 (30%) of 30 patients were treated with
      antibiotics that may be effective against S. lugdunensis. S. lugdunensis may be
      an unrecognized yet infrequent cause of urinary tract infection.

PMID- 11825991
TI  - Genotyping of clinical methicillin-susceptible Staphylococcus aureus isolates in
      a Dutch teaching hospital.
AB  - Methicillin-susceptible Staphylococcus aureus isolates, recovered from 204
      patients in our hospital in a 22-month period, were characterized by pulsed-field
      gel electrophoresis. Among the multiple S. aureus types six clonal lineages
      dominated, comprising isolates from 158 patients. Despite the limited genetic
      variation, cross-transmission was made plausible only sporadically.

PMID- 11825992
TI  - Use of 16S rRNA sequencing for identification of Actinobacillus ureae isolated
      from a cerebrospinal fluid sample.
AB  - Actinobacillus ureae, previously Pasteurella ureae, has on rare occasions been
      described as a cause of human infection. Owing to its rarity, it may not be
      easily identified in clinical microbiology laboratories by standard tests. This
      report describes a patient with acute bacterial meningitis due to A. ureae. The
      identity of the isolate was determined by means of DNA sequence analysis of a
      portion of the 16S rRNA gene.

PMID- 11825993
TI  - In vitro activities of broad-spectrum cephalosporins against nonmeningeal
      isolates of Streptococcus pneumoniae: MIC interpretation using NCCLS M100-S12
      recommendations.
AB  - Publication of the NCCLS M100-S12 document in January 2002 introduced ceftriaxone
      and cefotaxime MIC interpretative breakpoints of < or =1 microg/ml (susceptible),
      2 microg/ml (intermediate), and > or =4 microg/ml (resistant) for nonmeningeal
      isolates of Streptococcus pneumoniae. To estimate the effect of these breakpoint
      changes on clinical laboratory susceptibility testing results, nonmeningeal
      pneumococcal isolate (blood and respiratory) data from The Surveillance Network
      Database-USA, an electronic surveillance database, for the years 1996 to 2000
      were collated and studied. Of 9,863 nonmeningeal isolates tested against
      ceftriaxone, 82.7% were susceptible, 13.2% were intermediate, and 4.1% were
      resistant by the M100-S11 NCCLS breakpoints (2001); by M100-S12 breakpoints,
      95.9% of the isolates were susceptible, 3.1% were intermediate, and 1.0% were
      resistant. Of 10,777 nonmeningeal isolates tested against cefotaxime, 79.2% were
      susceptible, 14.3% were intermediate, and 6.5% were resistant by M100-S11
      breakpoints; by M100-S12 breakpoints, 93.5% were susceptible, 4.2% were
      intermediate, and 2.3% were resistant. Overall, the new M100-S12 ceftriaxone and
      cefotaxime interpretative breakpoints for nonmeningeal isolates of S. pneumoniae
      decreased the number of isolates interpreted as intermediate by 10% and as
      resistant by 3 to 4%.

PMID- 11825994
TI  - Quantification of human immunodeficiency virus type 1 proviral DNA by using
      TaqMan technology.
AB  - A protocol for quantification of human immunodeficiency virus type 1 (HIV-1)
      proviral DNA with the TaqMan technology was developed and validated. The assay
      was specific for HIV-1, with an analytic sensitivity of 10 copies and a linear
      dynamic range of >6 logs. Viral RNA levels, when at a stable state, were highly
      correlated with proviral DNA levels in 80 specimens of 18 HIV-infected children.

PMID- 11825995
TI  - PCR m typing: a new method for rapid typing of group a streptococci.
AB  - A new approach for the M-typing of Streptococcus pyogenes is reported.
      Oligonucleotide primers were used in a PCR to amplify the N-terminal region of
      the emm gene. The presence of the PCR amplification product is associated with
      the corresponding M serotype. This technique offers potential advantages over
      other molecular typing methods.

PMID- 11825996
TI  - Rapid real-time PCR for determination of penicillin susceptibility in
      pneumococcal meningitis, including culture-negative cases.
AB  - A novel real-time PCR-hybridization assay was developed for the rapid (<1 h)
      detection of penicillin susceptibility in Streptococcus pneumoniae. When applied
      to 24 pneumococcal DNA-positive cerebrospinal fluid extracts, penicillin
      sensitive S. pneumoniae was detected in all instances. Real-time PCR proved more
      sensitive than culture, microscopy, or antigen detection and provided
      susceptibility data even in culture-negative cases.

PMID- 11825997
TI  - Community-acquired bacteremic Acinetobacter pneumonia in tropical Australia is
      caused by diverse strains of Acinetobacter baumannii, with carriage in the throat
      in at-risk groups.
AB  - Acinetobacter isolates from eight subjects with community-acquired Acinetobacter
      pneumonia (CAAP), a major cause of fatal community-acquired pneumonia in tropical
      Australia, were phenotypically and genotypically confirmed by pulsed-field gel
      electrophoresis analysis to be broadly diverse Acinetobacter baumannii strains.
      Wet-season throat carriage of A. baumannii was found in 10% of community
      residents with excess levels of alcohol consumption, the major at-risk group for
      CAAP.

PMID- 11825998
TI  - Septicemia due to Pasteurella pneumotropica: 16S rRNA sequencing for diagnosis
      confirmation.
AB  - Bacteremia due to Pasteurella pneumotropica occurs infrequently. We report a case
      of septicemia in a 72-year-old woman who had no underlying illness. The
      microorganism was isolated from 10 blood cultures and identified by conventional
      and molecular methods. This is the first reported case of P. pneumotropica
      septicemia in an immunocompetent patient. The history of P. pneumotropica
      diseases in animals and humans and their varied clinical features are reviewed.

PMID- 11825999
TI  - Molecular analysis of Neorickettsia risticii in adult aquatic insects in
      Pennsylvania, in horses infected by ingestion of insects, and isolated in cell
      culture.
AB  - Upon ingestion of adult aquatic insects, horses developed clinical signs of
      Potomac horse fever, and Neorickettsia risticii was isolated from the blood. 16S
      rRNA and 51-kDa antigen gene sequences from blood, isolates, and caddis flies fed
      to the horses were identical, proving oral transmission of N. risticii from
      caddis flies to horses.

PMID- 11826000
TI  - Type IV longus pilus of enterotoxigenic Escherichia coli: occurrence and
      association with toxin types and colonization factors among strains isolated in
      Argentina.
AB  - The longus type IV pilus structural gene (lngA) was sought among 217 clinical
      enterotoxigenic Escherichia coli (ETEC) strains isolated in Argentina. lngA was
      present in 20.7% of the isolates and was highly associated with ETEC producing
      heat-stable toxin and the most common colonization factors. The prevalence of
      longus among ETEC strains in Argentina was comparable to that of colonization
      factor antigen I (CFA/I), CFA/II, and CFA/IV in other regions of the world.

PMID- 11826001
TI  - Specific identification of Listeria welshimeri and Listeria monocytogenes by PCR
      assays targeting a gene encoding a fibronectin-binding protein.
AB  - We have cloned and sequenced a Listeria welshimeri DNA fragment homologous to the
      previously described fibronectin-binding protein-encoding gene (fbp) of Listeria
      monocytogenes (P. Gilot, Y. Jossin, and J. Content, J. Med. Microbiol., 49:887
      896, 2000). This L. welshimeri DNA fragment expresses a 24.8-kDa protein that
      binds to human fibronectin. Based on the fbp sequences, we developed novel PCR
      assays for the identification of L. welshimeri and L. monocytogenes.

PMID- 11826002
TI  - Immune responses to the Mycobacterium tuberculosis-specific antigen ESAT-6 signal
      subclinical infection among contacts of tuberculosis patients.
AB  - Diagnosis of latent Mycobacterium tuberculosis infection is considered essential
      for tuberculosis control but is hampered by the lack of specific reagents. We
      report that strong recognition of tuberculosis complex-specific antigen ESAT-6 by
      healthy household contacts of tuberculosis patients correlates with the
      subsequent development of active tuberculosis during a 2-year follow-up period.

PMID- 11826004
TI  - Evaluation of a rapid PCR-based epidemiological typing method for routine studies
      of Mycobacterium tuberculosis.
AB  - Restriction fragment length polymorphism (RFLP) based on the insertion sequence
      IS6110 is used to investigate episodes of suspected transmission of infection of
      tuberculosis but usually takes a number of weeks from receipt of request to
      obtain a result. Often investigations would benefit from a more rapid method,
      possibly one containing an amplification step. The method employed uses a simple
      DNA extraction followed by a PCR step involving a single primer. Restriction
      enzyme analysis was performed when the patterns obtained from the PCR products
      were indistinguishable, especially when only single similar-size bands were
      obtained. The isolates used were strains of Mycobacterium tuberculosis submitted
      for epidemiological investigations as part of (i) possible contact-outbreak (22
      episodes involving between 2 and 20 patients), (ii) possible incidents of
      laboratory cross-contamination (21 episodes), and (iii) possible change in drug
      resistance pattern or a case of reinfection (1 patient). The PCR products giving
      similar patterns were then subjected to restriction enzyme analysis. In
      conclusion it has been shown that this method is rapid, with results within 1 to
      2 days of the request being received; is reproducible; and gives the same results
      as does RFLP. The restriction enzyme analysis stage has improved the efficiency
      of the technique.

PMID- 11826003
TI  - Differentiation between Mycobacterium farcinogenes and Mycobacterium senegalense
      strains based on 16S-23S ribosomal DNA internal transcribed spacer sequences.
AB  - 16S ribosomal DNA (rDNA) and 16S-23S internal transcribed spacer rDNA sequence
      analyses were performed on Mycobacterium farcinogenes and M. senegalense strains
      and 26 strains of other rapidly growing mycobacteria to investigate the
      phylogenetic structure of bovine farcy mycobacteria within the M. fortuitum
      complex. M. farcinogenes and M. senegalense were indistinguishable in their 5"
      end 16S rDNA but showed both considerable interspecies spacer sequence divergence
      and a high level of intraspecies sequence stability. A rapid detection assay
      using PCR and hybridization with species-specific probes was developed. The assay
      was specific among 46 species other than M. farcinogenes and M. senegalense and
      correctly identified all M. farcinogenes and M. senegalense strains. PCR- and 16S
      23S rDNA sequence-based detection will be a valuable approach for diagnosis of
      the causal agents of African bovine farcy in cattle.

PMID- 11826005
TI  - Lectin typing of Campylobacter concisus.
AB  - A total of 44 clinical isolates and the type strain of the putative pathogen
      Campylobacter concisus were grouped based on their reactions with plant lectins.
      The optimized lectin typing system used C. concisus strains proteolytically
      pretreated and subsequently typed by using a panel of four lectins. The system
      grouped all 45 strains into 13 lectin reaction patterns, leaving no strain
      untypeable due to autoagglutination. Lectin types were both stable and
      reproducible.

PMID- 11826006
TI  - Culture-negative endocarditis due to Chlamydia pneumoniae.
AB  - We report on the case of a 54-year-old woman diagnosed as having culture-negative
      endocarditis (clinical and histopathologic evidence compatible with a recent
      episode of endocarditis). The responsibility of Chlamydia pneumoniae in this
      episode of endocarditis was suggested by a serological study and was then
      confirmed by the positive results of PCR and in situ hybridization tests with
      aortic and mitral valves tissues. To our knowledge, this is the first case of
      endocarditis due to C. pneumoniae confirmed by molecular biology-based
      techniques.

PMID- 11826007
TI  - Cryptococcosis in a bottlenose dolphin (Tursiops truncatus) caused by
      Cryptococcus neoformans var. gattii.
AB  - We describe the first case of cryptococcosis caused by Cryptococcus neoformans
      var. gattii in a male Atlantic bottlenose dolphin (Tursiops truncatus). The
      dolphin showed clinical signs of tachypnea, transient dyspnea, and mild
      tachycardia and developed multiple hyperechoic nodules, parenchymal
      consolidation, and thickening of pleura. A diagnosis of bronchopneumonia with
      pleuritis was made. Itraconazole therapy was implemented for 120 days, and trough
      levels in serum were within or above the suggested therapeutic range. Titers of
      cryptococcal antigen in serum increased eightfold during therapy, and the case
      had a fatal outcome. Necropsy examination findings included enlarged pulmonary
      lymph nodes and extensive coalescing granulomatous lesions throughout both lungs.
      Histologic examination revealed numerous, spherical to ellipsoidal, mucicarmine
      positive, 3- to 14-microm, encapsulated, budding cells consistent with C.
      neoformans. Culture of the lung tissue yielded colonies of C. neoformans. The
      isolate was urease positive and nitrate negative and exhibited phenoloxidase
      activity. It was positive on canavanine-glycine-bromothymol blue agar. When
      tested by the Iatron serodiagnostic reagent kit (Iatron Laboratories, Inc.), it
      was shown to belong to serotype B.

PMID- 11826008
TI  - Soft tissue infection with Absidia corymbifera in a patient with idiopathic
      aplastic anemia.
AB  - We describe a case of primary cutaneous mucormycosis (zygomycosis) in a patient
      with idiopathic aplastic anemia which responded to surgical debridement and
      therapy with liposomal amphotericin B. The tissue removed at surgery showed dense
      infiltration with fungal hyphae on histopathological examination. Primary
      cultures of tissue on solid media were negative, but Absidia corymbifera was
      isolated from unprocessed tissue placed in brain heart infusion broth.

PMID- 11826009
TI  - Human infections due to Mycobacterium lentiflavum.
AB  - Three cases of human disease due to Mycobacterium lentiflavum are reported. In
      the first, the mycobacterium was responsible for chronic pulmonary disease in an
      elderly woman; in the second, it gave rise to cervical lymphadenitis in a child;
      and in the third, it caused a liver abscess in a young AIDS patient.

PMID- 11826010
TI  - Evaluation of wet-prep motility test for presumptive identification of bacillus
      species.

PMID- 11826011
TI  - Cyclospora in Guatemala: further considerations.

PMID- 11826012
TI  - Rapid laboratory diagnostics during the winter respiratory virus season.

PMID- 11826013
TI  - Detection of rpoB mutations in Mycobacterium tuberculosis with LightCycler
      technology.

PMID- 11826015
TI  - Ampicillin-sensitive, imipenem-resistant strains of Enterococcus faecium.

PMID- 11826014
TI  - Poor accuracy of rapid diagnostic tests and misdiagnosis of imported malaria: are
      PCR-based reference laboratories the answer?

PMID- 11826016
TI  - Familial adult renal neoplasia.
AB  - Our understanding of the molecular mechanisms underlying the tumorigenesis of
      renal cell carcinoma (RCC) has partially come from studies of RCC related
      familial cancer syndromes such as von Hippel-Lindau (VHL) disease and hereditary
      papillary RCC (HPRC). These studies have led to the identification of RCC related
      genes, which, besides allowing accurate diagnosis of these diseases, have been
      found mutated or abnormally expressed in the sporadic counterparts of these
      familial renal tumours. To date, a number of renal tumour related syndromes have
      been described. We review recent advances in this field and discuss a genetic
      approach to managing familial cases of renal tumours occasionally encountered by
      cancer geneticists and urologists.

PMID- 11826017
TI  - Preimplantation genetic diagnosis in clinical practice.
AB  - Preimplantation genetic diagnosis (PGD) represents an alternative to prenatal
      diagnosis and allows selection of unaffected IVF embryos for establishing
      pregnancies in couples at risk for transmitting a genetic disorder.

PMID- 11826018
TI  - The null oncogene hypothesis and protection from cancer.
AB  - Tumour progression involves the inactivation of tumour suppressor genes and the
      activation of proto-oncogenes. Inactivation of both copies of a tumour suppressor
      gene is required for carcinogenesis, while germline deletion or inactivation of
      one copy results in an increase in the risk of cancer and is responsible for many
      of the known hereditary cancer syndromes. In contrast, activation of only one
      copy of a proto-oncogene is required for carcinogenesis. Germline deletion or
      inactivation of one copy of a proto-oncogene halves the risk of activation at
      this locus. We propose that studies of high risk cancer patients will show such
      "null oncogene" mutations.

PMID- 11826019
TI  - National study of microphthalmia, anophthalmia, and coloboma (MAC) in Scotland:
      investigation of genetic aetiology.
AB  - We report an epidemiological and genetic study attempting complete ascertainment
      of subjects with microphthalmia, anophthalmia, and coloboma (MAC) born in
      Scotland during a 16 year period beginning on 1 January 1981. A total of 198
      cases were confirmed giving a minimum live birth prevalence of 19 per 100 000.
      One hundred and twenty-two MAC cases (61.6%) from 115 different families were
      clinically examined and detailed pregnancy, medical, and family histories
      obtained. A simple, rational, and apparently robust classification of the eye
      phenotype was developed based on the presence or absence of a defect in closure
      of the optic (choroidal) fissure. A total of 85/122 (69.7%) of cases had optic
      fissure closure defects (OFCD), 12/122 (9.8%) had non-OFCD, and 25/122 (20.5%)
      had defects that were unclassifiable owing to the severity of the corneal or
      anterior chamber abnormality. Segregation analysis assuming single and multiple
      incomplete ascertainment, respectively, returned a sib recurrence risk of 6% and
      10% in the whole group and 8.1% and 13.3% in the OFCD subgroup. Significant
      recurrence risks were found in both unilateral and bilateral disease. In four
      families, one parent had an OFCD, two of which were new diagnoses in asymptomatic
      subjects. All recurrences in first degree relatives occurred in the OFCD group
      with a single first cousin recurrence seen in the non-OFCD group. A total of
      84/122 of the MAC cases were screened for mutations in the coding regions of
      PAX6, CHX10, and SIX3. No pathogenic mutations were identified in the OFCD cases.
      A single PAX6 homeodomain missense mutation was identified in a subject with
      partial aniridia that had been initially misclassified as coloboma.

PMID- 11826021
TI  - High frequency of skewed X inactivation in young breast cancer patients.
AB  - INTRODUCTION: Patients with invasive ovarian cancer were recently shown to have a
      higher frequency of skewed X chromosome inactivation in peripheral blood cells
      compared to patients with borderline cancer and controls. In this study, we
      analysed the X inactivation pattern in peripheral blood from 216 breast cancer
      patients. METHODS: X inactivation analysis was performed using HpaII predigestion
      of DNA followed by PCR of the highly polymorphic CAG repeat of the androgen
      receptor gene (AR), which amplifies the undigested inactive X chromosome only.
      The X inactivation pattern was classified as skewed when 90% or more of the cells
      preferentially used one X chromosome. RESULTS: Young breast cancer patients (27
      45 years) had a higher frequency of skewed X inactivation than young controls (13
      and 1%, respectively) (p=0.009), whereas no difference was found for middle aged
      and older patients compared to controls of a similar age. CONCLUSIONS: A germline
      mutation in an X linked tumour suppressor gene may give a proliferative advantage
      to cells with this mutation on the active X chromosome, thus causing skewed X
      inactivation and an increased risk for developing cancer. Another possible
      explanation could be that females with a constitutionally skewed X inactivation
      pattern are more susceptible to develop breast cancer because of an X linked low
      penetrance susceptibility allele that is affected by the inactivation pattern.

PMID- 11826020
TI  - A single amino acid substitution (D1441Y) in the carboxyl-terminal propeptide of
      the proalpha1(I) chain of type I collagen results in a lethal variant of
      osteogenesis imperfecta with features of dense bone diseases.
AB  - Osteogenesis imperfecta (OI) is characterised by brittle bones and caused by
      mutations in the type I collagen genes, COL1A1 and COL1A2. We identified a
      mutation in the carboxyl-terminal propeptide coding region of one COL1A1 allele
      in an infant who died with an OI phenotype that differed from the usual lethal
      form and had regions of increased bone density. The newborn female had dysmorphic
      facial features, including loss of mandibular angle. Bilateral upper and lower
      limb contractures were present with multiple fractures in the long bones and
      ribs. The long bones were not compressed and their ends were radiographically
      dense. She died after a few hours and histopathological studies identified
      extramedullary haematopoiesis in the liver, little lamellar bone formation,
      decreased osteoclasts, abnormally thickened bony trabeculae with retained
      cartilage in long bones, and diminished marrow spaces similar to those seen in
      dense bone diseases such as osteopetrosis and pycnodysostosis. The child was
      heterozygous for a COL1A1 4321G-->T transversion in exon 52 that changed a
      conserved aspartic acid to tyrosine (D1441Y). Abnormal proalpha1(I) chains were
      slow to assemble into dimers and trimers, and abnormal molecules were retained
      intracellularly for an extended period. The secreted type I procollagen molecules
      synthesised by cultured dermal fibroblasts were overmodified along the full
      length but had normal thermal stability. These findings suggest that the unusual
      phenotype reflected both a diminished amount of secreted type I procollagen and
      the presence of a population of stable and overmodified molecules that might
      support increased mineralisation or interfere with degradation of bone.

PMID- 11826023
TI  - Association between markers in chromosomal region 17q23 and young onset
      hypertension: a TDT study.

PMID- 11826022
TI  - Sensitivity of conformation sensitive gel electrophoresis in detecting mutations
      in Marfan syndrome and related conditions.
AB  - OBJECTIVE: It has been firmly established that mutations in the gene for
      fibrillin 1, FBN1, cause Marfan syndrome (MFS). FBN1 mutations can also cause
      other phenotypes, such as ectopia lentis (EL) and familial isolated thoracic
      aortic aneurysm and dissection (FAA). When the clinical presentation is typical,
      diagnosis of MFS is usually easy to make. However, there can be a marked
      phenotypic variation between affected subjects even in one family, and making the
      diagnosis can be challenging, especially in childhood. The objective of this
      study was to test the sensitivity of conformation sensitive gel electrophoresis
      (CSGE) for detecting mutations in FBN1 in MFS and related phenotypes. DESIGN:
      Setting up CSGE analysis for the FBN1 gene and testing the method first by
      screening coded samples from 17 MFS patients with previously detected FBN1
      mutations. We then used a test set consisting of 46 coded samples representing
      MFS, related phenotypes, and controls. RESULTS: Sixteen of the 17 known mutations
      were detected. Altogether 23 mutations were detected in a test set consisting of
      46 coded samples representing MFS, related phenotypes, and controls. Nineteen of
      the mutations were novel. The mutation was detected in 18 of the 20 MFS patients
      and in one patient with familial EL, but not in a patient with sporadic MASS
      syndrome, any of the five sporadic annuloaortic ectasia (AAE) patients, or any of
      the 15 controls. A FBN1 mutation was detected in four members of a
      multigeneration family with AAE, however. CONCLUSIONS: These results indicate
      that CSGE is highly sensitive for the detection of mutations in FBN1, and that
      molecular diagnostics is a useful means of confirming clinical diagnoses of MFS
      and related disorders. Further careful investigations are needed, however, in
      order to correlate the interfamilial and intrafamilial clinical variabilities of
      fibrillinopathies and mutations in FBN1.

PMID- 11826024
TI  - Paternal contribution to the risk for pre-eclampsia.

PMID- 11826025
TI  - Association of polymorphisms and allelic combinations in the tumour necrosis
      factor-alpha-complement MHC region with coronary artery disease.

PMID- 11826026
TI  - CTLA-4/CD28 gene region is associated with genetic susceptibility to coeliac
      disease in UK families.

PMID- 11826027
TI  - A common ancestral haplotype in carrier chromosomes from different ethnic
      backgrounds in vacuolating megalencephalic leucoencephalopathy with subcortical
      cysts.

PMID- 11826029
TI  - In vitro analysis of aminoglycoside therapy for the Arg120stop nonsense mutation
      in RP2 patients.

PMID- 11826028
TI  - A late onset variant of ataxia-telangiectasia with a compound heterozygous
      genotype, A8030G/7481insA.

PMID- 11826030
TI  - Okihiro syndrome and acro-renal-ocular syndrome: clinical overlap, expansion of
      the phenotype, and absence of PAX2 mutations in two new families.

PMID- 11826031
TI  - Branchio-oculo-facial syndrome and branchio-otic/branchio-oto-renal syndromes are
      distinct entities.

PMID- 11826032
TI  - Infantile spinal muscular atrophy variant with congenital fractures in a female
      neonate: evidence for autosomal recessive inheritance.

PMID- 11826033
TI  - Probable corticospinal tract control of spinal cord plasticity in the rat.
AB  - Descending activity from the brain shapes spinal cord reflex function throughout
      life, yet the mechanisms responsible for this spinal cord plasticity are poorly
      understood. Operant conditioning of the H-reflex, the electrical analogue of the
      spinal stretch reflex, is a simple model for investigating these mechanisms. An
      earlier study in the Sprague-Dawley rat showed that acquisition of an operantly
      conditioned decrease in the soleus H-reflex is not prevented by mid-thoracic
      transection of the ipsilateral lateral column (LC), which contains the
      rubrospinal, reticulospinal, and vestibulospinal tracts, and is prevented by
      transection of the dorsal column, which contains the main corticospinal tract
      (CST) and the dorsal column ascending tract (DA). The present study explored the
      effects of CST or DA transection on acquisition of an H-reflex decrease, and the
      effects of LC, CST, or DA transection on maintenance of an established decrease.
      CST transection prior to conditioning prevented acquisition of H-reflex decrease,
      while DA transection did not do so. CST transection after H-reflex decrease had
      been acquired led to gradual loss of the decrease over 10 days, and resulted in
      an H-reflex that was significantly larger than the original, naive H-reflex. In
      contrast, LC or DA transection after H-reflex decrease had been acquired did not
      affect maintenance of the decrease. These results, in combination with the
      earlier study, strongly imply that in the rat the corticospinal tract (CST) is
      essential for acquisition and maintenance of operantly conditioned decrease in
      the H-reflex and that other major spinal cord pathways are not essential. This
      previously unrecognized aspect of CST function gives insight into the processes
      underlying acquisition and maintenance of motor skills and could lead to novel
      methods for inducing, guiding, and assessing recovery of function after spinal
      cord injury.

PMID- 11826034
TI  - Neural noise can explain expansive, power-law nonlinearities in neural response
      functions.
AB  - Many phenomenological models of the responses of simple cells in primary visual
      cortex have concluded that a cell's firing rate should be given by its input
      raised to a power greater than one. This is known as an expansive power-law
      nonlinearity. However, intracellular recordings have shown that a different
      nonlinearity, a linear-threshold function, appears to give a good prediction of
      firing rate from a cell's low-pass-filtered voltage response. Using a model based
      on a linear-threshold function, Anderson et al. showed that voltage noise was
      critical to converting voltage responses with contrast-invariant orientation
      tuning into spiking responses with contrast-invariant tuning. We present two
      separate results clarifying the connection between noise-smoothed linear
      threshold functions and power-law nonlinearities. First, we prove analytically
      that a power-law nonlinearity is the only input-output function that converts
      contrast-invariant input tuning into contrast-invariant spike tuning. Second, we
      examine simulations of a simple model that assumes instantaneous spike rate is
      given by a linear-threshold function of voltage and voltage responses include
      significant noise. We show that the resulting average spike rate is well
      described by an expansive power law of the average voltage (averaged over
      multiple trials), provided that average voltage remains less than about 1.5 SDs
      of the noise above threshold. Finally, we use this model to show that the noise
      levels recorded by Anderson et al. are consistent with the degree to which the
      orientation tuning of spiking responses is more sharply tuned relative to the
      orientation tuning of voltage responses. Thus neuronal noise can robustly
      generate power-law input-output functions of the form frequently postulated for
      simple cells.

PMID- 11826035
TI  - Myocardial ischemia recruits mechanically insensitive cardiac sympathetic
      afferents in cats.
AB  - Chest pain caused by myocardial ischemia is mediated by cardiac sympathetic
      afferents. Although silent nociceptors exist in somatic structures and some
      visceral organs, their presence in the heart remains uncertain. The present study
      examined the presence and the functional characteristics of mechanically
      insensitive cardiac sympathetic afferents using an electrical search technique.
      Single-unit activity of afferents innervating the left ventricle was recorded
      from the sympathetic chain in anesthetized cats. Cardiac afferents were
      identified initially with a stimulating electrode placed on the surface of the
      heart. Responses of cardiac afferents to mechanical stimuli, 5 min of myocardial
      ischemia, and topical application of bradykinin (1-10 microg/ml) and lactic acid
      (10-50 microg/ml) were then determined. Ischemia activated all 38 mechanically
      insensitive afferents and 17 of 25 mechanically sensitive afferents. The
      mechanically sensitive afferents typically were spontaneously active and had a
      smaller receptive field and a slightly faster conduction velocity. On the other
      hand, the mechanically insensitive afferents were slow conducting C fibers and
      had a large electrical receptive field on the epicardium. The response of 38
      mechanically insensitive afferents to ischemia [2.83 +/- 0.14 (SD) imp/s] was
      significantly greater than that of 17 mechanically sensitive afferents (from 0.41
      +/- 0.05 to 0.74 +/- 0.15 imp/s). The mechanically insensitive afferents also
      exhibited a greater response to topical application of bradykinin or lactic acid
      in a concentration-dependent manner. This study provides important new evidence
      that the heart is innervated by silent sympathetic afferents, which are activated
      profoundly by myocardial ischemia. These data also suggest that the mechanically
      insensitive sympathetic afferents may function as cardiac nociceptors.

PMID- 11826036
TI  - Long-term potentiation in direct perforant path projections to the hippocampal
      CA3 region in vivo.
AB  - The perforant path constitutes the primary projection system relaying information
      from the neocortex to the hippocampal formation. Long-term synaptic potentiation
      (LTP) in the perforant path projections to the dentate gyrus is well
      characterized. However, surprisingly few studies have addressed the mechanisms
      underlying LTP induction in the direct perforant path projections to the
      hippocampus. Here we investigate the role of N-methyl-D-aspartate (NMDA) and
      opioid receptors in the induction of LTP in monosynaptic medial and lateral
      perforant path projections to the CA3 region in adult pentobarbital sodium
      anesthetized rats. Similar to LTP observed at the medial perforant path-dentate
      gyrus synapse, medial perforant path-CA3 synapses display LTP that is blocked by
      both local and systemic administration of the competitive NMDA receptor
      antagonist (+/-)-3-(2-carboxypiperazin-4-yl) propyl-1-phosphonic acid [(+/-)
      CPP]. By contrast, LTP induced at the lateral perforant path-CA3 synapses is not
      blocked by either local or systemic administration of this NMDA receptor
      antagonist. The induction of LTP at lateral perforant path-CA3 synapses, which is
      blocked by the opioid receptor antagonist naloxone, is also blocked by the
      selective mu opioid receptor antagonist Cys(2)-Tyr(3)-Orn(5)-Pen(7)-amide (CTOP),
      but not the selective delta opioid receptor antagonist naltrindole (NTI). CTOP
      was without effect on the induction of medial perforant path-CA3 LTP. The
      selective sensitivity of lateral perforant path-CA3 LTP to mu-opioid receptor
      antagonists corresponds with the distribution of mu-opioid receptors within the
      stratum lacunosum-moleculare of area CA3 where perforant path projections to CA3
      terminate. These data indicate that both lateral and medial perforant path
      projections to the CA3 region display LTP, and that LTP induction in medial and
      lateral perforant path-CA3 synapses are differentially sensitive to NMDA receptor
      and mu-opioid receptor antagonists. This suggests a role for opioid, but not NMDA
      receptors in the induction of LTP at lateral perforant path projections to the
      hippocampal formation.

PMID- 11826037
TI  - Evidence that the superior colliculus participates in the feedback control of
      saccadic eye movements.
AB  - There is general agreement that saccades are guided to their targets by means of
      a motor error signal, which is produced by a local feedback circuit that
      calculates the difference between desired saccadic amplitude and an internal copy
      of actual saccadic amplitude. Although the superior colliculus (SC) is thought to
      provide the desired saccadic amplitude signal, it is unclear whether the SC
      resides in the feedback loop. To test this possibility, we injected muscimol into
      the brain stem region containing omnipause neurons (OPNs) to slow saccades and
      then determined whether the firing of neurons at different sites in the SC was
      altered. In 14 experiments, we produced saccadic slowing while simultaneously
      recording the activity of a single SC neuron. Eleven of the 14 neurons were
      saccade-related burst neurons (SRBNs), which discharged their most vigorous burst
      for saccades with an optimal amplitude and direction (optimal vector). The
      optimal directions for the 11 SRBNs ranged from nearly horizontal to nearly
      vertical, with optimal amplitudes between 4 and 17 degrees. Although muscimol
      injections into the OPN region produced little change in the optimal vector, they
      did increase mean saccade duration by 25 to 192.8% and decrease mean saccade peak
      velocity by 20.5 to 69.8%. For optimal vector saccades, both the acceleration and
      deceleration phases increased in duration. However, during 10 of 14 experiments,
      the duration of deceleration increased as fast as or faster than that of
      acceleration as saccade duration increased, indicating that most of the increase
      in duration occurred during the deceleration phase. SRBNs in the SC changed their
      burst duration and firing rate concomitantly with changes in saccadic duration
      and velocity, respectively. All SRBNs showed a robust increase in burst duration
      as saccadic duration increased. Five of 11 SRBNs also exhibited a decrease in
      burst peak firing rate as saccadic velocity decreased. On average across the
      neurons, the number of spikes in the burst was constant. There was no consistent
      change in the discharge of the three SC neurons that did not exhibit bursts with
      saccades. Our data show that the SC receives feedback from downstream saccade
      related neurons about the ongoing saccades. However, the changes in SC firing
      produced in our study do not suggest that the feedback is involved with producing
      motor error. Instead, the feedback seems to be involved with regulating the
      duration of the discharge of SRBNs so that the desired saccadic amplitude signal
      remains present throughout the saccade.

PMID- 11826038
TI  - Novel excitatory actions of galanin on rat cholinergic basal forebrain neurons:
      implications for its role in Alzheimer's disease.
AB  - Galanin, a 29-amino-acid neuropeptide, is generally viewed as an inhibitory
      neuromodulator in a variety of central systems. Galanin expression is upregulated
      in the cholinergic basal forebrain nuclei in Alzheimer's disease (AD) and is
      postulated to play an important role in memory and cognitive function. In this
      study, application of galanin to acutely dissociated rat neurons from the basal
      forebrain nucleus diagonal band of Broca (DBB), caused a decrease in whole cell
      voltage-activated currents in a majority of cells. Galanin reduces a suite of
      potassium currents, including calcium-activated potassium (I(C)), the delayed
      rectifier (I(K)), and transient outward potassium (I(A)) conductances, but not
      calcium or sodium currents. Under current-clamp conditions, application of
      galanin evoked an increase in excitability and a loss of accommodation in
      cholinergic DBB neurons. Using single-cell RT-PCR technique, we determined that
      galanin actions were specific to cholinergic, but not GABAergic DBB neurons The
      notion that galanin plays a deleterious role in AD is based, in part, on galanin
      hyperinnervation of cholinergic cells in the basal forebrain of AD patients, its
      ability to depress acetylcholine release and its inhibitory actions at other CNS
      sites. However, our results suggest that by virtue of its excitatory actions on
      cholinergic neurons, galanin may in fact play a compensatory role by augmenting
      the release of acetylcholine from remaining cholinergic basal forebrain neurons.
      This action might serve to delay the progression of AD pathology linked to a
      reduction in central cholinergic tone.

PMID- 11826039
TI  - Differential effect of ethanol on NMDA EPSCs in pyramidal cells in the posterior
      cingulate cortex of juvenile and adult rats.
AB  - Ethanol (EtOH) is a potent inhibitor of N-methyl-D-aspartate (NMDA) receptor
      mediated activity in a number of brain areas, and recent studies have indicated
      that this inhibitory effect of ethanol is more powerful in the juvenile brain
      compared with the adult brain. However, previous direct developmental comparisons
      have been limited to studies of extracellular responses in the hippocampus. To
      begin an assessment of the mechanisms underlying this developmental sensitivity,
      we assessed the inhibitory effect of EtOH on NMDA receptor-mediated synaptic
      transmission in neocortical slices from adult (95-135 days old) and juvenile (28
      32 days old) rats using the whole cell patch-clamp recording technique. In the
      presence of 6,7-dinitroquinoxaline-2,3-dione (20 microM) and bicuculline
      methiodine (20 microM), NMDA receptor-mediated excitatory postsynaptic currents
      were isolated from pyramidal cells of the posterior cingulate cortex (PCC). In
      slices from juvenile rats 5, 10, 30, and 60 mM EtOH reduced the mean amplitude of
      NMDA receptor-mediated EPSCs by 11, 22, 35, and 46%, respectively. However, the
      same concentrations of EtOH inhibited the mean amplitude of EPSCs by only 4, 8,
      15, and 31% in slices from adult rats. This developmental difference in the
      potency of EtOH against NMDA receptor-mediated EPSCs was also observed when the
      holding potential of the neurons was increased to +30 mV, although the inhibitory
      effect of ethanol on adult neurons was diminished at that voltage. These results
      provide a cellular analysis of the enhanced potency of ethanol against NMDA
      receptor-mediated EPSCs in neocortical cells from juvenile animals compared with
      adults.

PMID- 11826040
TI  - Acute effect of an incision on mechanosensitive afferents in the plantar rat
      hindpaw.
AB  - The purpose of this study was to examine which primary afferent fibers are
      sensitized to mechanical stimuli after an experimental surgical incision to the
      glabrous skin of the rat hindpaw. Afferent fibers teased from the L(5) dorsal
      root or the tibial nerve were recorded in anesthetized rats. The mechanical
      response properties of each fiber were characterized before and 45 min after an
      incision (or sham procedure) within the mechanical receptive field. Sensitization
      is characterized by an expansion of the mechanical receptive field, an increase
      in background activity, an increase in response magnitude, or a decrease in
      response threshold. After incision, the background activity and response
      properties of Abeta-fibers (n = 9) to mechanical stimuli were unchanged. Four of
      13 mechanosensitive Adelta-fibers exhibited sensitization after the incision;
      response threshold decreased, response magnitude increased, or receptive field
      size increased. Background activity of Adelta-fibers was not increased by the
      incision. Sensitization was observed in 4 of 18 mechanosensitive C-fibers 45 min
      after the incision. Background activity of C-fibers was not increased by the
      incision. In a group of mechanically insensitive afferent fibers (MIAs), 3 of 7
      Adelta-fibers and 4 of 10 C-fibers sensitized 45 min after incision. Response
      threshold was decreased in only 2 of 17 MIAs; receptive field size increased in 7
      of 17 MIAs. Abeta-fibers did not sensitize after the incision, and only 8 of 31
      (26%) mechanosensitive Adelta- and C-fibers gave evidence of sensitization. In a
      group of MIA Adelta- and C-fibers, a greater percentage of 17 fibers studied
      (41%) were sensitized after incision. In this model, the principal effect of an
      incision, when examined 45 min after the insult, is an increase in receptive
      field size of the afferents, particularly those characterized as MIAs. To the
      extent that the mechanical hyperalgesia characterized in the same model is
      initiated in the periphery, it would appear that spatial summation of modestly
      increased response magnitude is important to the development of hyperalgesia.

PMID- 11826041
TI  - Characterization of Adelta- and C-fibers innervating the plantar rat hindpaw one
      day after an incision.
AB  - Primary hyperalgesia after tissue injury is suggested to result from
      sensitization of primary afferent fibers, but sensitization to mechanical stimuli
      has been difficult to demonstrate. In the companion study, sensitization of
      mechano-responsive Adelta- and C-fibers did not explain pain behaviors 45 min
      after an incision in the rat hindpaw. In the present study, we examined
      mechanical response properties of Adelta- and C-fibers innervating the glabrous
      skin of the plantar hindpaw in rats 1 day after an incision or sham procedure. In
      behavioral experiments, median withdrawal thresholds to von Frey filaments were
      reduced from 522 mN before to 61 mN 2 and 20 h after incision; median withdrawal
      thresholds after sham procedure were stable (522 mN). Responses to a nonpunctate
      mechanical stimulus were increased after incision. In neurophysiological
      experiments in these same rats, 67 single afferent fibers were characterized from
      the left tibial nerve 1 day after sham procedure (n = 39) or incision (n = 28);
      electrical stimulation was used as the search stimulus to identify a
      representative population of Adelta- and C-fibers. In the incision group, 11
      fibers (39%) had spontaneous activity with frequencies ranging from 0.03 to 39.3
      imp/s; none were present in the sham group. The median response threshold of
      Adelta-fibers was less in the incision (56 mN, n = 13) compared with sham (251
      mN, n = 26) group, mainly because the proportion of mechanically insensitive
      afferents (MIAs) was less (8 vs. 54% after sham procedure). Median C-fiber
      response thresholds were similar in incised (28 mN, n = 15) and sham rats (56 mN,
      n = 13). Responsiveness to monofilaments was significantly enhanced in Adelta
      fibers 1 day after incision; stimulus response functions of C-fibers after
      incision and after sham procedure did not differ significantly. Only Adelta
      fibers but not C-fibers sensitized to the nonpunctate mechanical stimulus. The
      size of receptive fields was increased in Adelta- and C-fibers 1 day after
      incision. The results indicate that sensitization of Adelta- and C-fibers is
      apparent 1 day after incision. Because sensitization of afferent fibers to
      mechanical stimuli correlated with behavioral results, sensitization may
      contribute to the reduced withdrawal threshold after incision. Spontaneous
      activity in Adelta- and C-fibers may account for nonevoked pain behavior and may
      also contribute to mechanical hyperalgesia by amplifying responses centrally.

PMID- 11826042
TI  - Synergistic enhancement of glutamate-mediated responses by serotonin and
      forskolin in adult mouse spinal dorsal horn neurons.
AB  - Glutamate is the major excitatory amino acid neurotransmitter in the CNS,
      including the neocortex, hippocampus, and spinal cord. Normal synaptic
      transmission is mainly mediated by glutamate AMPA and/or kainate receptors.
      Glutamate N-methyl-D-aspartate (NMDA) receptors are normally inactive and only
      activated when a sufficient postsynaptic depolarization is induced by the
      activity. Here we show that in sensory synapses of adult mouse, some synaptic
      responses (26.3% of a total of 38 experiments) between primary afferent fibers
      and dorsal horn neurons are almost completely mediated by NMDA receptors. Dorsal
      root stimulation did not elicit any detectable AMPA/kainate receptor-mediated
      responses in these synapses. Unlike young spinal cord, serotonin alone did not
      produce any long-lasting synaptic enhancement in adult spinal dorsal horn
      neurons. However, co-application of the adenylyl cyclase activator forskolin and
      serotonin (5-HT) produced long-lasting enhancement, including the recruitment of
      functional AMPA receptor-mediated responses. Calcium-sensitive, calmodulin
      regulated adenylyl cyclases (AC1, AC8) are required for the enhancement.
      Furthermore the thresholds for generating action potential responses were
      decreased, and, in many cases, co-application of forskolin and 5-HT led to the
      generation of action potentials by previously subthreshold stimulation of primary
      afferent fibers in the presence of the NMDA receptor blocker 2-amino-5
      phosphonovaleric acid. Our results suggest that pure NMDA synapses exist on
      sensory neurons in adult spinal cord and that they may contribute to functional
      sensory transmission. The synergistic recruitment of functional AMPA responses by
      5-HT and forskolin provides a new cellular mechanism for glutamatergic synapses
      in mammalian spinal cord.

PMID- 11826043
TI  - NMDA-induced calcium loads recycle across the mitochondrial inner membrane of
      hippocampal neurons in culture.
AB  - Mitochondria sequester N-methyl-D-aspartate (NMDA)-induced Ca(2+) loads and
      regulate the shape of intracellular Ca(2+) concentration ([Ca(2+)](i)) responses
      in neurons. When isolated mitochondria are exposed to high [Ca(2+)](,) Ca(2+)
      enters the matrix via the uniporter and returns to the cytosol by Na(+)/Ca(2+)
      exchange. Released Ca(2+) may re-enter the mitochondrion recycling across the
      inner membrane dissipating respiratory energy. Ca(2+) recycling, the continuous
      uptake and release of Ca(2+) by mitochondria, has not been described in intact
      neurons. Here we used single-cell microfluorimetry to measure [Ca(2+)](i) and
      mitochondrially targeted aequorin to measure matrix Ca(2+) concentration
      ([Ca(2+)](mt)) to determine whether Ca(2+) recycles across the mitochondrial
      inner membrane in intact neurons following treatment with NMDA. We used ruthenium
      red and CGP 37157 to block uptake via the uniporter and release via Na(+)/Ca(2+)
      exchange, respectively. As predicted by the Ca(2+) recycling hypothesis, blocking
      the uniporter immediately following challenge with 200 microM NMDA produced a
      rapid and transient increase in cytosolic Ca(2+) without a corresponding increase
      in matrix Ca(2+). Blocking mitochondrial Ca(2+) release produced the opposite
      effect, depressing cytosolic Ca(2+) levels and prolonging the time for matrix
      Ca(2+) levels to recover. The Ca(2+) recycling hypothesis uniquely predicts these
      reciprocal changes in the Ca(2+) levels between the two compartments. Ca(2+)
      recycling was not detected following treatment with 20 microM NMDA. Thus Ca(2+)
      recycling across the inner membrane was more pronounced following treatment with
      a high relative to a low concentration of NMDA, consistent with a role in Ca(2+)
      dependent neurotoxicity.

PMID- 11826044
TI  - Changes in gene expression and neuronal phenotype in brain stem pain modulatory
      circuitry after inflammation.
AB  - Recent studies indicate that descending pain modulatory pathways undergo time
      dependent changes in excitability following inflammation involving both
      facilitation and inhibition. The cellular and molecular mechanisms of these
      phenomena are unclear. In the present study, we examined N-methyl-D-aspartate
      (NMDA) receptor gene expression and neuronal activity in the rostral ventromedial
      medulla (RVM), a pivotal structure in pain modulatory circuitry, after complete
      Freund's adjuvant (CFA)-induced hindpaw inflammation. The reverse transcription
      polymerase chain reaction analysis indicated that there was an upregulation of
      mRNAs encoding NMDA receptor subunits in the RVM after inflammation. The increase
      in the NR1, NR2A, and NR2B receptor mRNAs started at 5 h, maintained for 1-7 days
      (P < 0.05-0.001) and returned to the control level at 14 days after inflammation.
      Western blot analysis indicated that the protein translation products of the NR2A
      subunit were also increased (P < 0.01). In single-unit extracellular recordings,
      we correlated RVM neuronal activity with the paw withdrawal response in rats with
      inflammation. We describe these RVM cells as on-, off-, and neutral-like cells
      because of their similarity to previous studies in which neuronal responses were
      correlated with tail-flick nocifensive behavior in the absence of inflammation.
      In contrast to previous studies in the absence of inflammation, using tail flick
      as a behavioral correlate, fewer off-like cells in naive animals exhibited a
      complete pause before the paw withdrawal to a noxious thermal stimulus. The
      percentage of cells showing a pause of activity after noxious stimulation was
      further reduced after inflammation (chi(2) P < 0.0001 vs. naive rats). Continuous
      neuronal recordings (3-6.5 h) revealed a phenotypic switch of RVM neurons during
      the development of inflammation: 11/15 neutral-like cells initially unresponsive
      to noxious stimuli exhibited and maintained response profiles characteristic of
      pain modulatory neurons (became off-like: n = 5; became on-like: n = 6). Neutral
      like cells recorded in noninflamed animals did not show response profile changes
      during continuous recordings (5-5.5 h, n = 7). A population study (n = 165)
      confirmed an increase in on- and off-like cells and a decrease in neutral-like
      cells at 24 h after inflammation as compared with naive rats (P < 0.001). These
      results suggest that enhanced NMDA receptor activation mediates time-dependent
      changes in excitability of RVM pain modulatory circuitry. The functional
      phenotypic switch of RVM neurons provides a novel mechanism underlying activity
      dependent plasticity and enhanced net descending inhibition after inflammation.

PMID- 11826045
TI  - Nitric oxide blocks fast, slow, and persistent Na+ channels in C-type DRG neurons
      by S-nitrosylation.
AB  - C-type dorsal root ganglion (DRG) neurons express three types of Na+ currents:
      fast TTX-sensitive, slow TTX-resistant, and persistent TTX-resistant Na+
      currents. The nitric oxide (NO) donors papa-NONOate and S-nitroso-N-acetyl-DL
      penicillamine inhibit all three types of Na+ currents. The NO scavenger
      hemoglobin abolished the effects of papa-NONOate on Na+ currents, indicating that
      NO or NO-related species inhibit these Na+ currents. NO donor inhibition of all
      three types of Na+ currents was reversed by washout. Incubation of neurons with 8
      bromo cGMP, a membrane-permeable analogue of cGMP, and cG-PKI, an inhibitor of
      cGMP-dependent protein kinase, had no effect on papa-NONOate-mediated Na+ current
      block, demonstrating that Na+ current inhibition is independent of cGMP.
      Alkylation of free thiols with N-ethylmaleimide prevented the actions of papa
      NONOate, suggesting that NO, or a related reactive nitrogen species, modifies
      sulfhydryl groups on Na+ channels or a closely associated protein. Papa-NONOate
      mediated block of Na+ currents is not due to a hyperpolarizing shift in steady
      state voltage-dependent inactivation. The absence of NO-mediated enhancement of
      slow inactivation in fast and slow Na+ channels indicates that NO does not
      inhibit fast and slow Na+ channels by facilitating the transition to a slow
      inactivated state. These results demonstrate that inhibition of Na+ currents is
      not due to the modulation of fast and slow sodium channel inactivation. Taken
      together, these results show that NO or NO-related products modify the sulfhydryl
      groups on Na+ channels and inhibit Na+ currents by blocking the channel
      conductance.

PMID- 11826046
TI  - Calcium waves and closure of potassium channels in response to GABA stimulation
      in Hermissenda type B photoreceptors.
AB  - Classical conditioning of Hermissenda crassicornis requires the paired
      presentation of a conditioned stimulus (light) and an unconditioned stimulus
      (turbulence). Light stimulation of photoreceptors leads to production of
      diacylglycerol, an activator of protein kinase C, and inositol triphosphate
      (IP(3)), which releases calcium from intracellular stores. Turbulence causes hair
      cells to release GABA onto the terminal branches of the type B photoreceptor. One
      prior study has shown that GABA stimulation produces a wave of calcium that
      propagates from the terminal branches to the soma and raises the possibility that
      two sources of calcium are required for memory storage. GABA stimulation also
      causes an inhibitory postsynaptic potential (IPSP) followed by a late
      depolarization and increase in input resistance, whose cause has not been
      identified. A model was developed of the effect of GABA stimulation on the
      Hermissenda type B photoreceptor to evaluate the currents underlying the late
      depolarization and to evaluate whether a calcium wave could propagate from the
      terminal branches to the soma. The model included GABA(A), GABA(B), and calcium
      sensitive potassium leak channels; calcium dynamics including release of calcium
      from intracellular stores; and the biochemical reactions leading from GABA(B)
      receptor activation to IP(3) production. Simulations show that it is possible for
      a wave of calcium to propagate from the terminal branches to the soma. The wave
      is initiated by IP(3)-induced calcium release but propagation requires release
      through the ryanodine receptor channel where IP(3) concentration is small. Wave
      speed is proportional to peak calcium concentration at the crest of the wave,
      with a minimum speed of 9 microM/s in the absence of IP(3). Propagation ceases
      when peak concentration drops below 1.2 microM; this occurs if the rate of
      calcium pumping into the endoplasmic reticulum is too large. Simulations also
      show that both a late depolarization and an increase in input resistance occur
      after GABA stimulation. The duration of the late depolarization corresponds to
      the duration of potassium leak channel closure. Neither the late depolarization
      nor the increase in input resistance are observed when a transient calcium
      current and a hyperpolarization-activated current are added to the model as
      replacement for closure of potassium leak channels. Thus the late depolarization
      and input resistance elevation can be explained by a closure of calcium-sensitive
      leak potassium currents but cannot be explained by a transient calcium current
      and a hyperpolarization-activated current.

PMID- 11826047
TI  - Dopamine modulates exocytosis independent of Ca(2+) entry in melanotropic cells.
AB  - Dopamine is a known inhibitor of pituitary melanotropic cells. It reduces Ca(2+)
      influx by hyperpolarizing the cell membrane and by modulating high- and low
      voltage-activated (HVA and LVA) Ca(2+) channels. As a result, dopamine reduces
      the hormonal output of the cell. However, it is unknown how dopamine affects each
      of the four different HVA Ca(2+) channel types individually. Moreover, it is
      unknown whether dopamine interacts with exocytosis independent of Ca(2+)
      channels. Here we show that dopamine differentially modulates the HVA Ca(2+)
      channels and that it affects the stimulus-secretion coupling through a direct
      effect on the exocytotic machinery. Sustained L- and P-type Ba(2+) currents are
      reduced in amplitude and inactivating N- and Q-type currents acquire different
      activation and inactivation kinetics in the presence of dopamine. The Q-type
      current shows slow activation, which is a hallmark for direct G-protein
      modulation. We used membrane capacitance measurements to monitor exocytosis.
      Surprisingly, we find that the amount of exocytosis per step depolarization is
      not diminished by dopamine despite the reduction in Ca(2+) current. To test
      whether dopamine affects the release machinery downstream of Ca(2+) entry, we
      stimulated exocytosis by dialyzing cells with buffered high-Ca(2+) solutions.
      Dopamine increased the amount and the rate of exocytosis. In the first 90 s, the
      rate of secretion was increased two- to threefold, but it was normalized again at
      180 s, suggesting that predominantly vesicles that fuse early in the exocytotic
      phase are modulated by dopamine. Thus while Ca(2+) channels are inhibited by
      dopamine, the exocytotic machinery downstream of Ca(2+) influx is sensitized. As
      a result, release is more effectively stimulated by Ca(2+) influx during dopamine
      inhibition.

PMID- 11826048
TI  - Enhancement of multiple components of pursuit eye movement by microstimulation in
      the arcuate frontal pursuit area in monkeys.
AB  - Periarcuate frontal cortex is involved in the control of smooth pursuit eye
      movements, but its role remains unclear. To better understand the control of
      pursuit by the "frontal pursuit area" (FPA), we applied electrical
      microstimulation when the monkeys were performing a variety of oculomotor tasks.
      In agreement with previous studies, electrical stimulation consisting of a train
      of 50-microA pulses at 333 Hz during fixation of a stationary target elicited
      smooth eye movements with a short latency (approximately 26 ms). The size of the
      elicited smooth eye movements was enhanced when the stimulation pulses were
      delivered during the maintenance of pursuit. The enhancement increased as a
      function of ongoing pursuit speed and was greater during pursuit in the same
      versus opposite direction of the eye movements evoked at a site. If stimulation
      was delivered during pursuit in eight different directions, the elicited eye
      velocity was fit best by a model incorporating two stimulation effects: a
      directional signal that drives eye velocity and an increase in the gain of
      ongoing pursuit eye speed in all directions. Separate experiments tested the
      effect of stimulation on the response to specific image motions. Stimulation
      consisted of a train of pulses at 100 or 200 Hz delivered during fixation so that
      only small smooth eye movements were elicited. If the stationary target was
      perturbed briefly during microstimulation, normally weak eye movement responses
      showed strong enhancement. If delivered at the initiation of pursuit, the same
      microstimulation caused enhancement of the presaccadic initiation of pursuit for
      steps of target velocity that moved the target either away from the position of
      fixation or in the direction of the eye movement caused by stimulation at the
      site. Stimulation in the FPA increased the latency of saccades to stationary or
      moving targets. Our results show that the FPA has two kinds of effects on the
      pursuit system. One drives smooth eye velocity in a fixed direction and is
      subject to on-line gain control by ongoing pursuit. The other causes enhancement
      of both the speed of ongoing pursuit and the responses to visual motion in a way
      that is not strongly selective for the direction of pursuit. Enhancement may
      operate either at a single site or at multiple sites. We conclude that the FPA
      plays an important role in on-line gain control for pursuit as well as possibly
      delivering commands for the direction and speed of smooth eye motion.

PMID- 11826049
TI  - Neural processing of gravitoinertial cues in humans. III. Modeling tilt and
      translation responses.
AB  - All linear accelerometers measure gravitoinertial force, which is the sum of
      gravitational force (tilt) and inertial force due to linear acceleration
      (translation). Neural strategies must exist to elicit tilt and translation
      responses from this ambiguous cue. To investigate these neural processes, we
      developed a model of human responses and simulated a number of motion paradigms
      used to investigate this tilt/translation ambiguity. In this model, the
      separation of GIF into neural estimates of gravity and linear acceleration is
      accomplished via an internal model made up of three principal components: 1) the
      influence of rotational cues (e.g., semicircular canals) on the neural
      representation of gravity, 2) the resolution of gravitoinertial force into neural
      representations of gravity and linear acceleration, and 3) the neural
      representation of the dynamics of the semicircular canals. By combining these
      simple hypotheses within the internal model framework, the model mimics human
      responses to a number of different paradigms, ranging from simple paradigms, like
      roll tilt, to complex paradigms, like postrotational tilt and centrifugation. It
      is important to note that the exact same mechanisms can explain responses induced
      by simple movements as well as by more complex paradigms; no additional elements
      or hypotheses are needed to match the data obtained during more complex
      paradigms. Therefore these modeled response characteristics are consistent with
      available data and with the hypothesis that the nervous system uses internal
      models to estimate tilt and translation in the presence of ambiguous sensory
      cues.

PMID- 11826050
TI  - Circadian modulation of GABA function in the rat suprachiasmatic nucleus:
      excitatory effects during the night phase.
AB  - Gramicidin-perforated patch-clamp recordings were made from slices of the
      suprachiasmatic nucleus (SCN) of adult rats to characterize the role of gamma
      amino butyric acid (GABA) in the circadian timing system. During the day,
      activation of GABA(A) receptors hyperpolarized the membrane of SCN neurons.
      During the night, however, activation of GABA(A) receptors either hyperpolarized
      or depolarized the membrane. These night-restricted depolarizations in a large
      subset of SCN neurons were capable of triggering spikes and thus appeared to be
      excitatory. The GABA(A) reversal potentials of SCN neurons revealed a significant
      day-night difference with more depolarized GABA(A) reversal potentials during the
      night than during the day. The emergence of depolarizing GABA(A)-mediated
      responses in a subset of SCN neurons at night can be ascribed to a depolarizing
      shift in GABA(A) reversal potential. The GABA(A) receptor antagonist bicuculline
      (12.5 microM) increased the spontaneous firing rate of all SCN neurons during the
      day, indicating that spontaneous GABA(A)-mediated inputs inhibited the SCN
      neurons during this period. The effect of bicuculline (12.5 microM) on the
      spontaneous firing rate of SCN neurons during the night was heterogeneous due to
      the mixture of depolarizing and hyperpolarizing GABA(A)-mediated inputs during
      this period. We conclude that GABA uniformly acts as an inhibitory transmitter
      during the day but excites a large subset of SCN neurons at night. This day-night
      modulation of GABAergic neurotransmission provides the SCN with a time-dependent
      gating mechanism that may counteract propagation of excitatory signals throughout
      the biological clock at day but promotes it at night.

PMID- 11826051
TI  - Comparison of cortico-cortical and cortico-collicular signals for the generation
      of saccadic eye movements.
AB  - Many neurons in the frontal eye field (FEF) and lateral intraparietal (LIP) areas
      of cerebral cortex are active during the visual-motor events preceding the
      initiation of saccadic eye movements: they respond to visual targets, increase
      their activity before saccades, and maintain their activity during intervening
      delay periods. Previous experiments have shown that the output neurons from both
      LIP and FEF convey the full range of these activities to the superior colliculus
      (SC) in the brain stem. These areas of cerebral cortex also have strong
      interconnections, but what signals they convey remains unknown. To determine what
      these cortico-cortical signals are, we identified the LIP neurons that project to
      FEF by antidromic activation, and we studied their activity during a delayed
      saccade task. We then compared these cortico-cortical signals to those sent
      subcortically by also identifying the LIP neurons that project to the
      intermediate layers of the SC. Of 329 FEF projection neurons and 120 SC
      projection neurons, none were co-activated by both FEF and SC stimulation. FEF
      projection neurons were encountered more superficially in LIP than SC projection
      neurons, which is consistent with the anatomical projection of many cortical
      layer III neurons to other cortical areas and of layer V neurons to subcortical
      structures. The estimated conduction velocities of FEF projection neurons (16.7
      m/s) were significantly slower that those of SC projection neurons (21.7 m/s),
      indicating that FEF projection neurons have smaller axons. We identified three
      main differences in the discharge properties of FEF and SC projection neurons:
      only 44% of the FEF projection neurons changed their activity during the delayed
      saccade task compared with 69% of the SC projection neurons; only 17% of the task
      related FEF projection neurons showed saccadic activity, whereas 42% of the SC
      projection neurons showed such increases; 78% of the FEF projection neurons had a
      visual response but no saccadic activity, whereas only 55% of the SC projection
      neurons had similar activity. The FEF and SC projection neurons had three
      similarities: both had visual, delay, and saccadic activity, both had stronger
      delay and saccadic activity with visually guided than with memory-guided
      saccades, and both had broadly tuned responses for disparity stimuli, suggesting
      that their visual receptive fields have a three-dimensional configuration. These
      observations indicate that the activity carried between parietal and frontal
      cortical areas conveys a spectrum of signals but that the preponderance of
      activity conveyed might be more closely related to earlier visual processing than
      to the later saccadic stages that are directed to the SC.

PMID- 11826052
TI  - Gaze-, eye-, and head-movement dynamics during closed- and open-loop gaze
      pursuit.
AB  - Horizontal step-ramp stimuli were used to examine gaze-, eye-, and head-movement
      dynamics during head-unrestrained pursuit in two rhesus monkeys. In a first
      series of experiments, we characterized and compared head-restrained (HR) and 
      unrestrained (HU) pursuit responses to unpredictable, nonperiodic, constant
      velocity (20-80 degrees/s) stimuli. When the head was free to move, both monkeys
      used a combination of eye and head motion to initially fixate and then pursue the
      target. The pursuit responses (i.e., gaze responses) were highly stereotyped and
      nearly identical among the HR and HU conditions for a given step-ramp stimulus.
      In the HU condition, initial eye and initial head acceleration tended to increase
      as a function of target velocity but did not vary systematically with initial
      target eccentricity. In a second series of experiments, step-ramp stimuli (40
      degrees/s) were presented, and, approximately 125 ms after pursuit onset, a
      constant retinal velocity error (RVE) was imposed for a duration of 300 ms. In
      each monkey, HR and HU gaze velocity was similarly affected by stabilizing the
      target with respect to the monkey's fovea (i.e., RVE = 0 degrees/s) and by moving
      the target with constant retinal velocity errors (i.e., RVE = +/- 10 degrees/s).
      In the HU condition, changes in both eye and head velocity trajectories
      contributed to the observed gaze velocity responses to imposed RVEs. We conclude
      that eye and head movements are not independently controlled during HU pursuit
      but rather are controlled, at least in part, by a shared upstream controller
      within the pursuit pathways.

PMID- 11826054
TI  - Pacemaker neurons for the theta rhythm and their synchronization in the
      septohippocampal reciprocal loop.
AB  - Hippocampal theta (4-10 Hz) oscillation represents a well-known brain rhythm
      implicated in spatial cognition and memory processes. Its cellular mechanisms
      remain a matter of debate, and previous computational work has focused mostly on
      mechanisms intrinsic to the hippocampus. On the other hand, experimental data
      indicate that GABAergic cells in the medial septum play a pacemaker role for the
      theta rhythm. We have used biophysical modeling to address two major questions
      raised by the septal pacemaker hypothesis: what is the ion channel mechanism for
      the single-cell pacemaker behavior and how do these cells become synchronized?
      Our model predicts that theta oscillations of septal GABAergic cells depend
      critically on a low-threshold, slowly inactivating potassium current. Network
      simulations show that theta oscillations are not coherent in an isolated
      population of pacemaker cells. Robust synchronization emerges with the addition
      of a second GABAergic cell population. Such a reciprocally inhibitory circuit can
      be realized by the hippocampo-septal feedback loop.

PMID- 11826053
TI  - mAChRs in the grasshopper brain mediate excitation by activation of the AC/PKA
      and the PLC second-messenger pathways.
AB  - The species-specific sound production of acoustically communicating grasshoppers
      can be stimulated by pressure injection of both nicotinic and muscarinic agonists
      into the central body complex and a small neuropil situated posterior and dorsal
      to it. To determine the role of muscarinic acetylcholine receptors (mAChRs) in
      the control of acoustic communication behavior and to identify the second
      messenger pathways affected by mAChR-activation, muscarinic agonists and membrane
      permeable drugs known to interfere with specific mechanisms of intracellular
      signaling pathways were pressure injected to identical sites in male grasshopper
      brains. Repeated injections of small volumes of muscarine elicited stridulation
      of increasing duration associated with decreased latencies. This suggested an
      accumulation of excitation over time that is consistent with the suggested role
      of mAChRs in controlling courtship behavior: to provide increasing arousal
      leading to higher intensity of stridulation and finally initiating a mating
      attempt. At sites in the brain where muscarine stimulation was effective,
      stridulation could be evoked by forskolin, an activator of adenylate cyclase
      (AC); 8-Br-cAMP-activating protein kinase A (PKA); and 3-isobuty-1
      methylxanthine, leading to the accumulation of endogenously generated cAMP
      through inhibition of phosphodiesterases. This suggested that mAChRs mediate
      excitation by stimulating the AC/cAMP/PKA pathway. In addition, muscarine
      stimulated stridulation was inhibited by 2'-5'-dideoxyadenonsine and SQ 22536,
      two inhibitors of AC; H-89 and Rp-cAMPS, two inhibitors of PKA; and by U-73122
      and neomycin, two agents that inhibit phospholipase C (PLC) by independent
      mechanisms. Because the inhibition of AC, PKA, or PLC by various individually
      applied substances entirely suppressed muscarine-evoked stridulation in a number
      of experiments, activation of both pathways, AC/cAMP/PKA and
      PLC/IP(3)/diacylglycerine, appeared to be necessary to mediate the excitatory
      effects of mAChRs. With these studies on an intact "behaving" grasshopper
      preparation, we present physiological relevance for mAChR-evoked excitation
      mediated by sequential activation of the AC- and PLC-initiated signaling pathways
      that has been reported in earlier in vitro studies.

PMID- 11826055
TI  - Potential role of medullary raphe-spinal neurons in cutaneous vasoconstriction:
      an in vivo electrophysiological study.
AB  - In rabbits, raphe magnus/pallidus neurons form a link in the CNS pathway
      regulating changes in cutaneous blood flow elicited by nociceptive stimulation
      and activation of the central nucleus of the amygdala. To characterize relevant
      raphe-spinal neurons, we performed extracellular recordings from the rostral
      medullary raphe nuclei in anesthetized, paralyzed, mechanically ventilated
      rabbits. All studied neurons were antidromically activated from the dorsolateral
      funiculus of the spinal cord (C(8)-T(2)). Of 129 studied neurons, 40% were
      silent. The remaining neurons discharged spontaneously at 0.3-29 Hz. Nociceptive
      stimulation (lip squeeze with pliers) excited 63 (49%), inhibited 9 (7%), and did
      not affect 57 (44%) neurons. The same stimulation also elicited falls in ear
      pinna blood flow. In neurons activated by the stimulation, the increase in
      discharge preceded the fall in flow. Electrical stimulation of the spinal
      trigeminal tract excited 61/63 nociception-activated neurons [onset latencies
      range: 6-75 ms, mean: 28 +/- 3 (SE) ms], inhibited 9/9 nociception-inhibited
      neurons (onset latencies range: 9-85 ms, mean: 32 +/- 10 ms), and failed to
      affect 55/57 neurons insensitive to nociceptive stimulation. Neurons insensitive
      to nociceptive/trigeminal stimulation were also insensitive to nonnociceptive
      tactile stimulation and to electrical stimulation of the amygdala. They were
      either silent (32/45) or discharged regularly at low frequencies. They possessed
      long-duration action potentials (1.26 +/- 0.08 ms) and slow-conducting axons (6.0
      +/- 0.5 m/s). These neurons may be serotonergic raphe-spinal cells. They do not
      appear to be involved in nociceptive-related cutaneous vascular control. Of the
      63 neurons sensitive to nociceptive and trigeminal tract stimulation, 35 also
      responded to tactile stimulation (wide receptive field). These neurons possessed
      short action potentials (0.80 +/- 0.03 ms) and fast-conducting axons (30.3 +/-
      3.1 m/s). In this subpopulation, electrical stimulation of the amygdala activated
      nearly all neurons tested (10/12), with a mean onset latency of 34 +/- 3 ms. The
      remaining 28 neurons sensitive to nociceptive and trigeminal stimulation did not
      respond to tactile stimuli and were mainly unaffected by amygdala stimulation. It
      may be that fast-conducting raphe-spinal neurons, with wide multimodal receptive
      fields and with input from the central nucleus of the amygdala, constitute the
      bulbo-spinal link in the CNS pathway regulating cutaneous blood flow in response
      to nociceptive and alerting stimuli.

PMID- 11826056
TI  - Partial ablations of the flocculus and ventral paraflocculus in monkeys cause
      linked deficits in smooth pursuit eye movements and adaptive modification of the
      VOR.
AB  - The vestibuloocular reflex (VOR) generates compensatory eye movements to
      stabilize visual images on the retina during head movements. The amplitude of the
      reflex is calibrated continuously throughout life and undergoes adaptation, also
      called motor learning, when head movements are persistently associated with image
      motion. Although the floccular-complex of the cerebellum is necessary for VOR
      adaptation, it is not known whether this function is localized in its anterior or
      posterior portions, which comprise the ventral paraflocculus and flocculus,
      respectively. The present paper reports the effects of partial lesions of the
      floccular-complex in five macaque monkeys, made either surgically or with
      stereotaxic injection of 3-nitropropionic acid (3-NP). Before and after the
      lesions, smooth pursuit eye movements were tested during sinusoidal and step-ramp
      target motion. Cancellation of the VOR was tested by moving a target exactly with
      the monkey during sinusoidal head rotation. The control VOR was tested during
      sinusoidal head rotation in the dark and during 30 degrees/s pulses of head
      velocity. VOR adaptation was studied by having the monkeys wear x2 or x0.25
      optics for 4-7 days. In two monkeys, bilateral lesions removed all of the
      flocculus except for parts of folia 1 and 2 but did not produce any deficits in
      smooth pursuit, VOR adaptation, or VOR cancellation. We conclude that the
      flocculus alone probably is not necessary for either pursuit or VOR learning. In
      two monkeys, unilateral lesions including a large fraction of the ventral
      paraflocculus produced small deficits in horizontal and vertical smooth pursuit,
      and mild impairments of VOR adaptation and VOR cancellation. We conclude that the
      ventral paraflocculus contributes to both behaviors. In one monkey, a bilateral
      lesion of the flocculus and ventral paraflocculus produced severe deficits smooth
      pursuit and VOR cancellation, and a complete loss of VOR adaptation. Considering
      all five cases together, there was a strong correlation between the size of the
      deficits in VOR learning and pursuit. We found the strongest correlation between
      the behavior deficits and the size of the lesion of the ventral paraflocculus, a
      weaker but significant correlation for the full floccular complex, and no
      correlation with the size of the lesion of the flocculus. We conclude that 1)
      lesions of the floccular complex cause linked deficits in smooth pursuit and VOR
      adaptation, and 2) the relevant portions of the structure are primarily in the
      ventral paraflocculus, although the flocculus may participate.

PMID- 11826057
TI  - Contribution of presynaptic Na(+) channel inactivation to paired-pulse synaptic
      depression in cultured hippocampal neurons.
AB  - Paired-pulse depression (PPD) of synaptic transmission is important for neuronal
      information processing. Historically, depletion of the readily releasable pool of
      synaptic vesicles has been proposed as the major component of PPD. Recent results
      suggest, however, that other mechanisms may be involved in PPD, including
      inactivation of presynaptic voltage-dependent sodium channels (NaChs), which may
      influence coupling of action potentials to transmitter release. In hippocampal
      cultures, we have examined the potential role and relative contribution of
      presynaptic NaCh inactivation in excitatory postsynaptic current (EPSC) PPD.
      Based on current- and voltage-clamp recordings from somas, our data suggest that
      NaCh inactivation could potentially participate in PPD. Paired stimulation of
      somatic action potentials (20- to 100-ms interval) results in subtle changes in
      action potential shape that are mimicked by low concentrations of tetrodotoxin
      (TTX) and that appear to be generated by a combination of fast and slow recovery
      from NaCh inactivation. Dilute concentrations of TTX dramatically depress
      glutamate release. However, we find evidence for only minimal contribution of
      NaCh inactivation to EPSC PPD under basal conditions. Hyperpolarization of
      presynaptic elements to speed recovery from inactivation or increasing the
      driving force on Na(+) ions through active NaChs had minimal effects on PPD while
      more robustly reversing the effects of pharmacological NaCh blockade. On the
      other hand, slight depolarization of the presynaptic membrane potential, by
      elevating extracellular [K(+)](o), significantly increased PPD and frequency
      dependent depression of EPSCs during short trains of action potentials. The
      results suggest that NaCh inactivation is poised to modulate EPSC amplitude with
      small tonic depolarizations that likely occur with physiological or
      pathophysiological activity.

PMID- 11826058
TI  - Fine temporal resolution of analytic phase reveals episodic synchronization by
      state transitions in gamma EEGs.
AB  - The analytic signal given by the Hilbert transform applied to an
      electroencephalographic (EEG) trace is a vector of instantaneous amplitude and
      phase at the temporal resolution of the digitizing interval (here 2 ms). The
      transform was applied after band-pass filtering for extracting the gamma band (20
      80 Hz in rabbits) to time series from up to 64 EEG channels recorded
      simultaneously from high-density arrays giving spatial "windows" of 4 x 4 to 6 x
      6 mm onto the visual, auditory, or somatosensory cortical surface. The time
      series of the analytic phase revealed phase locking for brief time segments in
      spatial patterns of nonzero phase values from multiple EEG that was punctuated by
      episodic phase decoherence. The derivative of the analytic phase revealed spikes
      occurring not quite simultaneously (within +/- 4 ms) across arrays aperiodically
      at mean rates in and below the theta range (3-7 Hz). Two measures of global
      synchronization over a group of channels were derived from analytic phase
      differences between pairs of channels on the same area of cortex. One was a
      synchronization index expressing phase locking. The other was a decoherence index
      estimating the variance in phase among multiple channels. Spectral analyses of
      the indices indicated that decoherence events recurred aperiodically at rates in
      and below the theta range of the EEGs. The results provide support for the
      hypothesis that neurons in mesoscopic neighborhoods in sensory cortices self
      organize their activity by synaptic interactions into wave packets that have
      spatial patterns of amplitude (AM) and phase (PM) modulation of their spatially
      coherent carrier waves in the gamma range and that form and dissolve
      aperiodically at rates in and below the theta range. Each AM pattern is formed by
      a nonlinear state transition in the cortical dynamics, as shown by spikes in the
      derivative. Phase locking within each PM pattern is not at zero phase lag but
      over a fixed distribution of phase values that is consistent with the radially
      symmetric phase gradients already reported called "phase cones" detected by
      Fourier-based methods. The insight is suggested that sensory cortices are
      bistable comparably to cardiac dynamics, with a diastolic state that accepts
      sensory input and an abrupt transition to a systolic state that transmits
      perceptual output. Further support for this inference will require improvements
      in methods for temporal resolution of the times of onset of spatial patterns of
      phase modulation.

PMID- 11826059
TI  - Properties of primary sensory (lemniscal) synapses in the ventrobasal thalamus
      and the relay of high-frequency sensory inputs.
AB  - The main role of the thalamus is to relay sensory inputs to the neocortex. In the
      primary somatosensory thalamus (ventrobasal thalamus), sensory inputs deliver
      tactile information through the medial lemniscus tract. The transmission of
      sensory information through this pathway is affected by behavioral state. For
      instance, the relay of high-frequency somatosensory inputs through the thalamus
      is suppressed during anesthesia or quiescent states but allowed during
      behaviorally activated states. This change may be due to the effects of
      modulators on the efficacy of lemniscal synapses. Here I show that lemniscal
      synapses of adult rodents studied in vitro produce large amplitude-highly secure
      unitary excitatory postsynaptic potentials (EPSPs), which depress in response to
      repetitive stimulation at frequencies >2 Hz. Acetylcholine and norepinephrine,
      which are important thalamic modulators, have no effect on the efficacy of
      lemniscal EPSPs but reduce evoked inhibitory postsynaptic potentials and
      corticothalamic EPSPs. Although acetylcholine and norepinephrine do not affect
      lemniscal synapses, the postsynaptic depolarization they produce on
      thalamocortical neurons serves to warrant the relay of lemniscal inputs at high
      frequency rates by bringing the depressed lemniscal EPSPs close to firing
      threshold. In conclusion, acetylcholine and norepinephrine released during
      activated states selectively enhance sensory transmission through the lemniscal
      pathway by depolarizing thalamocortical neurons and simultaneously depressing the
      other afferent pathways.

PMID- 11826060
TI  - Ionic basis of the resting membrane potential and action potential in the
      pharyngeal muscle of Caenorhabditis elegans.
AB  - The pharynx of C. elegans is a rhythmically active muscle that pumps bacteria
      into the gut of the nematode. This activity is maintained by action potentials,
      which qualitatively bear a resemblance to vertebrate cardiac action potentials.
      Here, the ionic basis of the resting membrane potential and pharyngeal action
      potential has been characterized using intracellular recording techniques. The
      resting membrane potential is largely determined by a K(+) permeability, and a
      ouabain-sensitive, electrogenic pump. As previously suggested, the action
      potential is at least partly dependent on voltage-gated Ca(2+) channels, as the
      amplitude was increased as extracellular Ca(2+) was increased, and decreased by L
      type Ca(2+) channel blockers verapamil and nifedipine. Barium caused a marked
      prolongation of action potential duration, suggesting that a calcium-activated
      K(+) current may contribute to repolarization. Most notably, however, we found
      that action potentials were abolished in the absence of external Na(+). This may
      be due, at least in part, to a Na(+)-dependent pacemaker potential. In addition,
      the persistence of action potentials in nominally free Ca(2+), the inhibition by
      Na(+) channel blockers procaine and quinidine, and the increase in action
      potential frequency caused by veratridine, a toxin that alters activation of
      voltage-gated Na(+) channels, point to the involvement of a voltage-gated Na(+)
      current. Voltage-clamp analysis is required for detailed characterization of this
      current, and this is in progress. Nonetheless, these observations are quite
      surprising in view of the lack of any obvious candidate genes for voltage-gated
      Na(+) channels in the C. elegans genome. It would therefore be informative to re
      evaluate the data from these homology searches, with the aim of identifying the
      gene(s) conferring this Na(+), quinidine, and veratridine sensitivity to the
      pharynx.

PMID- 11826061
TI  - Cerebellar nodulectomy impairs spatial memory of vestibular and optokinetic
      stimulation in rabbits.
AB  - Natural vestibular and optokinetic stimulation were used to investigate the
      possible role of the cerebellar nodulus in the regulation and modification of
      reflexive eye movements in rabbits. The nodulus and folium 9d of the uvula were
      destroyed by surgical aspiration. Before and after nodulectomy the vertical and
      horizontal vestibuloocular reflexes (VVOR, HVOR) were measured during sinusoidal
      vestibular stimulation about the longitudinal (roll) and vertical (yaw) axes.
      Although the gain of the HVOR (G(HVOR) = peak eye movement velocity/peak head
      velocity) was not affected by the nodulectomy, the gain of the VVOR (G(VVOR)) was
      reduced. The gains of the vertical and horizontal optokinetic reflexes (G(VOKR),
      G(HOKR)) were measured during monocular, sinusoidal optokinetic stimulation (OKS)
      about the longitudinal and vertical axes. Following nodulectomy, there was no
      reduction in G(VOKR) or G(HOKR). Long-term binocular OKS was used to generate
      optokinetic afternystagmus, OKAN II, that lasts for hours. After OKAN II was
      induced, rabbits were subjected to static pitch and roll, to determine how the
      plane and velocity of OKAN II is influenced by a changing vestibular environment.
      During static pitch, OKAN II slow phase remained aligned with earth-horizontal.
      This was true for normal and nodulectomized rabbits. During static roll, OKAN II
      remained aligned with earth-horizontal in normal rabbits. During static roll in
      nodulectomized rabbits, OKAN II slow phase developed a centripetal vertical
      drift. We examined the suppression and recovery of G(VVOR) following exposure to
      conflicting vertical OKS for 10-30 min. This vestibular-optokinetic conflict
      reduced G(VVOR) in both normal and nodulectomized rabbits. The time course of
      recovery of G(VVOR) after conflicting OKS was the same before and after
      nodulectomy. In normal rabbits, the head pitch angle, at which peak OKAN II
      velocity occurred, corresponded to the head pitch angle maintained during long
      term OKS. If the head was maintained in a "pitched-up" or "pitched-down"
      orientation during long-term OKS, the subsequently measured OKAN II peak velocity
      occurred at the same orientation. This was not true for nodulectomized rabbits,
      who had OKAN II peak velocities at head pitch angles independent of those
      maintained during long-term OKS. We conclude that the nodulus participates in the
      regulation of compensatory reflexive movements. The nodulus also influences
      "remembered" head position in space derived from previous optokinetic and
      vestibular stimulation.

PMID- 11826062
TI  - Neural correlates of the precedence effect in the inferior colliculus: effect of
      localization cues.
AB  - The precedence effect (PE) is an auditory phenomenon involved in suppressing the
      perception of echoes in reverberant environments, and is thought to facilitate
      accurate localization of sound sources. We investigated physiological correlates
      of the PE in the inferior colliculus (IC) of anesthetized cats, with a focus on
      directional mechanisms for this phenomenon. We used a virtual space (VS)
      technique, where two clicks (a "lead" and a "lag") separated by a brief time
      delay were each filtered through head-related transfer functions (HRTFs). For
      nearly all neurons, the response to the lag was suppressed for short delays and
      recovered at long delays. In general, both the time course and the directional
      patterns of suppression resembled those reported in free-field studies in many
      respects, suggesting that our VS simulation contained the essential cues for
      studying PE phenomena. The relationship between the directionality of the
      response to the lead and that of its suppressive effect on the lag varied a great
      deal among IC neurons. For a majority of units, both excitation produced by the
      lead and suppression of the lag response were highly directional, and the two
      were similar to one another. For these neurons, the long-lasting inhibitory
      inputs thought to be responsible for suppression seem to have similar spatial
      tuning as the inputs that determine the excitatory response to the lead. Further,
      the behavior of these neurons is consistent with psychophysical observations that
      the PE is strongest when the lead and the lag originate from neighboring spatial
      locations. For other neurons, either there was no obvious relationship between
      the directionality of the excitatory lead response and the directionality of
      suppression, or the suppression was highly directional whereas the excitation was
      not, or vice versa. For these neurons, the excitation and the suppression
      produced by the lead seem to depend on different mechanisms. Manipulation of the
      directional cues (such as interaural time and level differences) contained in the
      lead revealed further dissociations between excitation and suppression.
      Specifically, for about one-third of the neurons, suppression depended on
      different directional cues than did the response to the lead, even though the
      directionality of suppression was similar to that of the lead response when all
      cues were present. This finding suggests that the inhibitory inputs causing
      suppression may originate in part from subcollicular auditory nuclei processing
      different directional cues than the inputs that determine the excitatory response
      to the lead. Neurons showing such dissociations may play an important role in the
      PE when the lead and the lag originate from very different directions.

PMID- 11826063
TI  - Modeling the excitability of mammalian nerve fibers: influence of afterpotentials
      on the recovery cycle.
AB  - Human nerve fibers exhibit a distinct pattern of threshold fluctuation following
      a single action potential known as the recovery cycle. We developed geometrically
      and electrically accurate models of mammalian motor nerve fibers to gain insight
      into the biophysical mechanisms that underlie the changes in axonal excitability
      and regulate the recovery cycle. The models developed in this study incorporated
      a double cable structure, with explicit representation of the nodes of Ranvier,
      paranodal, and internodal sections of the axon as well as a finite impedance
      myelin sheath. These models were able to reproduce a wide range of experimental
      data on the excitation properties of mammalian myelinated nerve fibers. The
      combination of an accurate representation of the ion channels at the node (based
      on experimental studies of human, cat, and rat) and matching the geometry of the
      paranode, internode, and myelin to measured morphology (necessitating the double
      cable representation) were needed to match the model behavior to the experimental
      data. Following an action potential, the models generated both depolarizing (DAP)
      and hyperpolarizing (AHP) afterpotentials. The model results support the
      hypothesis that both active (persistent Na(+) channel activation) and passive
      (discharging of the internodal axolemma through the paranodal seal) mechanisms
      contributed to the DAP, while the AHP was generated solely through active (slow
      K(+) channel activation) mechanisms. The recovery cycle of the fiber was
      dependent on the DAP and AHP, as well as the time constant of activation and
      inactivation of the fast Na(+) conductance. We propose that experimentally
      documented differences in the action potential shape, strength-duration
      relationship, and the recovery cycle of motor and sensory nerve fibers can be
      attributed to kinetic differences in their nodal Na(+) conductances.

PMID- 11826064
TI  - Corticostriatal combinatorics: the implications of corticostriatal axonal
      arborizations.
AB  - The complete striatal axonal arborizations of 16 juxtacellularly stained cortical
      pyramidal cells were analyzed. Corticostriatal neurons were located in the medial
      agranular or anterior cingulate cortex of rats. All axons were of the extended
      type and formed synaptic contacts in both the striosomal and matrix compartments
      as determined by counterstaining for the mu-opiate receptor. Six axonal
      arborizations were from collaterals of brain stem-projecting cells and the other
      10 from bilaterally projecting cells with no brain stem projections. The
      distribution of synaptic boutons along the axons were convolved with the average
      dendritic tree volume of spiny projection neurons to obtain an axonal innervation
      volume and innervation density map for each axon. Innervation volumes varied
      widely, with single axons occupying between 0.4 and 14.2% of the striatum
      (average = 4%). The total number of boutons formed by individual axons ranged
      from 25 to 2,900 (average = 879). Within the innervation volume, the density of
      innervation was extremely sparse but inhomogeneous. The pattern of innervation
      resembled matrisomes, as defined by bulk labeling and functional mapping
      experiments, superimposed on a low background innervation. Using this sample as
      representative of all corticostriatal axons, the total number of corticostriatal
      neurons was estimated to be 17 million, about 10 times the number of striatal
      projection neurons.

PMID- 11826065
TI  - Suppression of neural responses to nonoptimal stimuli correlates with tuning
      selectivity in macaque V1.
AB  - Neural responses in primary visual cortex (area V1) are selective for the
      orientation and spatial frequency of luminance-modulated sinusoidal gratings.
      Selectivity could arise from enhancement of the cell's response by preferred
      stimuli, suppression by nonoptimal stimuli, or both. Here, we report that the
      majority of V1 neurons do not only elevate their activity in response to
      preferred stimuli, but their firing rates are also suppressed by nonoptimal
      stimuli. The magnitude of suppression is similar to that of enhancement. There is
      a tendency for net response suppression to peak at orientations near orthogonal
      to the optimal for the cell, but cases where suppression peaks at oblique
      orientations are observed as well. Interestingly, selectivity and suppression
      correlate in V1: orientation and spatial frequency selectivity are higher for
      neurons that are suppressed by nonoptimal stimuli than for cells that are not.
      This finding is consistent with the idea that suppression plays an important role
      in the generation of sharp cortical selectivity. We show that nonlinear
      suppression is required to account for the data. However, the precise structure
      of the neural circuitry generating the suppressive signal remains unresolved. Our
      results are consistent with both feedback and (nonlinear) feed-forward
      inhibition.

PMID- 11826067
TI  - Distributed and concentration-invariant spatial representations of odorants by
      receptor neuron input to the turtle olfactory bulb.
AB  - We sought to characterize how odorants are represented at the level of afferent
      input to the olfactory bulb of the box turtle, a terrestrial reptile that, like
      mammals, detects airborne odorants. Using methods developed first in zebrafish,
      we selectively labeled olfactory receptor neurons with Calcium Green-1 dextran
      and imaged odorant-evoked input to glomeruli in vivo. Odorant representations
      were imaged at a glomerular level of resolution over a portion of the dorsal
      olfactory bulb and at a regional level of resolution over the entire dorsal
      surface. We report two new findings. First, even at low concentrations, odorants
      typically elicited input to a large fraction of all imaged glomeruli. Second,
      while the amplitude of the odorant-evoked input to glomeruli was concentration
      dependent, the relative pattern of input to the bulb changed only slightly over a
      concentration range of up to three log units. These results suggest the
      hypothesis that odorant representations in the turtle involve differential levels
      of input to many glomeruli, and that detecting relative patterns of distributed
      glomerular activation may be an important strategy for encoding odor quality
      independent of intensity.

PMID- 11826066
TI  - Functional independence of layer IV barrels.
AB  - Our aim was to investigate the patterns of functional inputs and outputs from
      individual barrels in the mouse somatosensory cortex, and to test the hypothesis
      that individual barrels in layer IV are functionally independent of direct inputs
      from neighboring barrels. In a mouse in vitro slice preparation of the barrel
      cortex, we recorded voltage-sensitive dye signals evoked in response to
      microstimulation of a single barrel. Activity propagated from the stimulated
      barrel to the supragranular layers, where it spread to activate several barrel
      columns. However, in no instance did activity propagate directly from the
      stimulated barrel to neighboring barrels. Neither suppression of GABAergic
      inhibition, nor activation of N-methyl-D-aspartate receptors, revealed direct
      interbarrel interactions. By contrast, microstimulation in the supra- or
      infragranular layers resulted in direct propagation of activity to neighboring
      barrel columns. We conclude that the neurons within individual barrels are
      functionally independent of direct inputs from neighboring barrels. This suggests
      that the response properties of layer IV barrel neurons are shaped primarily by
      their presynaptic thalamic afferents and by intrabarrel interactions, and that
      these responses are independent of direct inputs from neighboring barrels.

PMID- 11826068
TI  - D2 receptors inhibit the secretory process downstream from calcium influx in
      dopaminergic neurons: implication of K+ channels.
AB  - Dopaminergic (DAergic) neurons possess D2-like somatodendritic and terminal
      autoreceptors that modulate cellular excitability and dopamine (DA) release. The
      cellular and molecular processes underlying the rapid presynaptic inhibition of
      DA release by D2 receptors remain unclear. Using a culture system in which
      isolated DAergic neurons establish self-innervating synapses ("autapses") that
      release both DA and glutamate, we studied the mechanism by which presynaptic D2
      receptors inhibit glutamate-mediated excitatory postsynaptic currents (EPSCs).
      Action-potential evoked EPSCs were reversibly inhibited by quinpirole, a
      selective D2 receptor agonist. This inhibition was slightly reduced by the inward
      rectifier K(+) channel blocker barium, largely prevented by the voltage-dependent
      K(+) channel blocker 4-aminopyridine, and completely blocked by their combined
      application. The lack of a residual inhibition of EPSCs under these conditions
      argues against the implication of a direct inhibition of presynaptic Ca(2+)
      channels. To evaluate the possibility of a direct inhibition of the secretory
      process, spontaneous miniature EPSCs were evoked by the Ca(2+) ionophore
      ionomycin. Ionomycin-evoked release was insensitive to cadmium and dramatically
      reduced by quinpirole, providing evidence for a direct inhibition of quantal
      release at a step downstream to Ca(2+) influx through voltage-dependent Ca(2+)
      channels. Surprisingly, this effect of quinpirole on ionomycin-evoked release was
      blocked by 4-aminopyridine. These results suggest that D2 receptor activation
      decreases neurotransmitter release from DAergic neurons through a presynaptic
      mechanism in which K(+) channels directly inhibit the secretory process.

PMID- 11826069
TI  - Physiological properties of late inspiratory neurons and their possible
      involvement in inspiratory off-switching in cats.
AB  - To assess the functional significance of late inspiratory (late-I) neurons in
      inspiratory off-switching (IOS), membrane potential and discharge properties were
      examined in vagotomized, decerebrate cats. During spontaneous IOS, late-I neurons
      displayed large membrane depolarization and associated discharge of action
      potentials that started in late inspiration, peaked at the end of inspiration,
      and ended during postinspiration. Depolarization was decreased by iontophoresis
      of dizocilpine and eliminated by tetrodotoxin. Stimulation of the vagus nerve or
      the nucleus parabrachialis medialis (NPBM) also evoked depolarization of late-I
      neurons and IOS. Waves of spontaneous chloride-dependent inhibitory postsynaptic
      potentials (IPSPs) preceded membrane depolarization during early inspiration and
      followed during postinspiration and stage 2 expiration of the respiratory cycle.
      Iontophoresed bicuculline depressed the IPSPs. Intravenous dizocilpine caused a
      greatly prolonged inspiratory discharge of the phrenic nerve (apneusis) and
      suppressed late-inspiratory depolarization as well as early-inspiratory IPSPs,
      resulting in a small constant depolarization throughout the apneusis. NPBM or
      vagal stimulation after dizocilpine produced small, stimulus-locked excitatory
      postsynaptic potentials (EPSPs) in late-I neurons. Neurobiotin-labeled late-I
      neurons revealed immunoreactivity for glutamic acid decarboxylase as well as N
      methyl-D-aspartate (NMDA) receptors. These results suggest that late-I neurons
      are GABAergic inhibitory neurons, while the effects of bicuculline and
      dizocilpine indicate that they receive periodic waves of GABAergic IPSPs and
      glutamatergic EPSPs. The data lead to the conclusion that late-I neurons play an
      important inhibitory role in IOS. NMDA receptors are assumed to augment and/or
      synchronize late-inspiratory depolarization and discharge of late-I neurons,
      leading to GABA release and consequently off-switching of bulbar inspiratory
      neurons and phrenic motoneurons.

PMID- 11826070
TI  - Neural correlates of tasting concentrated quinine and sugar solutions.
AB  - Behavioral, ethological, and electrophysiological evidence suggests that the
      highly unpleasant, bitter taste of a concentrated quinine hydrochloride (QHCL)
      should activate the human amygdala. In the present study, healthy subjects tasted
      0.02 M QHCL or water while regional cerebral blood flow (rCBF) was assayed with
      H(2)(15)O PET. Subjects were also studied while tasting a pleasant sucrose
      solution and resting with eyes closed (ECR). Tasting QHCL significantly increased
      rCBF within the left amygdala relative to control conditions of tasting water and
      ECR. Sucrose and water caused small to moderate rCBF increases in the amygdala
      relative to ECR, but sucrose did not significantly increase activity within
      either amygdalae relative to water. In the frontal lobe, QHCL and sucrose both
      activated the right posterior orbitofrontal cortex (OFC) relative to water, but
      portions of the anterior OFC and inferior frontal pole showed valence specific
      responses to QHCL. These data indicate that the left amygdala responds robustly
      to QHCL and more moderately to nonaversive sapid stimuli, both pleasant and
      unpleasant gustatory stimuli activate the right posterior OFC, and the left
      inferior frontal pole/anterior OFC demonstrates valence-specific responses to
      aversive gustatory stimuli.

PMID- 11826071
TI  - Characterization of mitotic neurons derived from adult rat hypothalamus and brain
      stem.
AB  - Embryonic or neonatal rat neurons retain plasticity and are readily grown in
      tissue culture, but neurons of the adult brain were thought to be terminally
      differentiated and therefore difficult to culture. Recent studies, however,
      suggest that it may be possible to culture differentiated neurons from the
      hippocampus of adult rats. We modified these procedures to grow differentiated
      neurons from adult rat hypothalamus and brain stem. At day 7 in tissue culture
      and beyond, the predominant cell types in hypothalamic and brain stem cultures
      had a stellate morphology and could be subdivided into two distinct groups, one
      of which stained with antibodies to the immature neuron marker alpha-internexin,
      while the other stained with the astrocyte marker GFAP. The alpha-internexin
      positive cells were mitotic and grew to form a characteristic two-dimensional
      cellular network. These alpha-internexin positive cells coimmunostained for the
      neuronal markers MAP2, type III beta-tubulin, and tau, and also bound tetanus
      toxin, but were negative for the oligodendrocyte marker GalC and also for the
      neurofilament triplet proteins NF-L, NF-M, and NF-H, markers of more mature
      neurons. Patch-clamp analysis of these alpha-internexin positive cells revealed
      small Ca(2+) currents with a peak current of -0.5 +/- 0.1 pA/pF at a membrane
      potential of -20 mV (n = 5) and half-maximal activation at -30 mV (n = 5). Na(+)
      currents with a peak current density of -154.5 +/- 49.8 pA/pF at a membrane
      potential of -15 mV (n = 5) were also present. We also show that these cells can
      be frozen and regrown in tissue culture and that they can be efficiently infected
      by viral vectors. These cells therefore have the immunological and
      electrophysiological properties of immature mitotic neurons and should be useful
      in a variety of future studies of neuronal differentiation and function.

PMID- 11826072
TI  - Plastic changes in nociceptive transmission of the rat spinal cord with advancing
      age.
AB  - To understand characteristics of the pain system in the elderly, we investigated
      the electrophysiological properties of nociceptive neurons in the lumbar spinal
      dorsal horn of aged (29-34-mo old) and adult (7-13-mo old) rats. The responses of
      nociceptive neurons to noxious thermal stimulation, as well as the spontaneous
      firing rate, were significantly higher in the aged as compared with adult rats.
      Furthermore, the size of the high-threshold receptive field area of wide dynamic
      range neurons was larger (P < 0.01) and that of the low-threshold area was
      smaller (P < 0.05) in aged rats than in adult rats. The increased nociceptive
      neuronal activity in the aged rats correlated with the finding that the paw
      withdrawal latency was significantly shorter in the aged rats than those of the
      adult rats following heat stimulation of the hind paw (P < 0.05). Reversible
      local anesthetic block of descending pathways resulted in a dramatic increase in
      neuronal activity in adult rats but had little effect in aged rats. There was
      also a significant loss of serotoninergic and noradrenergic fibers in the spinal
      dorsal horn of the aged rats. These results demonstrate an age-related plasticity
      in spinal nociceptive processing that is related to impairment of descending
      modulatory pathways.

PMID- 11826073
TI  - Interactions between multiple rhythm generators produce complex patterns of
      oscillation in the developing rat spinal cord.
AB  - Neural networks capable of generating coordinated rhythmic activity form at early
      stages of development in the spinal cord. In this study, voltage-imaging
      techniques were used to examine the spatiotemporal pattern of rhythmic activity
      in transverse slices of lumbar spinal cord from embryonic and neonatal rats. Real
      time images were recorded in slices stained with the voltage-sensitive
      fluorescent dye RH414 using a 464-element photodiode array. Fluorescence signals
      showed spontaneous voltage oscillations with a frequency of 3 Hz. Simultaneous
      recordings of fluorescence and extracellular field potential demonstrated that
      the two signals oscillated with the same frequency and had a distinct phase
      relationship, indicating that the fluorescence changes represented changes in
      transmembrane potentials. The oscillations were reversibly blocked by cobalt (1
      mM), indicating a dependence on Ca(2+) influx through voltage-gated Ca(2+)
      channels. Extracellular field potentials revealed oscillations with the same
      frequency in both stained and unstained slices. Oscillations were apparent
      throughout a slice, although their amplitudes varied in different regions. The
      largest amplitude oscillations were produced in the lateral regions. To examine
      the spatial organization of rhythm-generating networks, slices were cut into
      halves and quarters. Each fragment continued to oscillate with the same frequency
      as intact slices but with smaller amplitudes. This finding suggested that rhythm
      generating networks were widely distributed and did not depend on long-range
      projections. In slices from neonatal rats, the oscillations exhibited a complex
      spatiotemporal pattern, with depolarizations alternating between mirror locations
      in the right and left sides of the cord. Furthermore, within each side
      depolarizations alternated between the lateral and medial regions. This medial
      lateral pattern was preserved in hemisected slices, indicating that pathways
      intrinsic to each side coordinated this activity. A different pattern of
      oscillation was observed in slices from embryos with synchronous 3-Hz
      oscillations occurring in limited regions. Our study demonstrated that rhythm
      generators were distributed throughout transverse sections of the lumbar spinal
      cord and exhibited a complex spatiotemporal pattern of coordinated rhythmic
      activity.

PMID- 11826074
TI  - Role of inhibition for temporal and spatial odor representation in olfactory
      output neurons: a calcium imaging study.
AB  - The primary olfactory brain center, the antennal lobe (AL) in insects or the
      olfactory bulb in vertebrates, is a notable example of a neural network for
      sensory processing. While physiological properties of the input, the olfactory
      receptor neurons, have become clearer, the operation of the network itself
      remains cryptic. Therefore we measured spatio-temporal odor-response patterns in
      the output neurons of the olfactory glomeruli using optical imaging in the
      honeybee Apis mellifera. We mapped these responses to identified glomeruli, which
      are the structural and functional units of the AL. Each odor evoked a complex
      spatio-temporal activity pattern of excited and inhibited glomeruli. These
      properties were odor- and glomerulus-specific and were conserved across
      individuals. We compared the spatial pattern of excited glomeruli to previously
      published signals, which derived mainly from the receptor neurons, and found that
      they appeared more confined, showing that inhibitory connections enhance the
      contrast between glomeruli in the AL. To investigate the underlying mechanisms,
      we applied GABA and the GABA-receptor antagonist picrotoxin (PTX). The results
      show the presence of two separate inhibitory networks: one is GABAergic and
      modulates overall AL activity, the other is PTX-insensitive and glomerulus
      specific. Inhibitory connections of the latter network selectively inhibit
      glomeruli with overlapping response profiles, in a way akin to "lateral"
      inhibition in other sensory systems. Selectively inhibited glomeruli need not be
      spatial neighbors. The net result is a globally modulated, contrast-enhanced and
      predictable representation of odors in the olfactory output neurons.

PMID- 11826075
TI  - Multisecond periodicities in basal ganglia firing rates correlate with theta
      bursts in transcortical and hippocampal EEG.
AB  - Multisecond oscillations in firing rate with periods in the range of 2-60 s
      (mean, 20-35 s) are present in 50-90% of spike trains from basal ganglia neurons
      recorded from locally anesthetized, immobilized rats. To determine whether these
      periodic oscillations are associated with similar periodicities in cortical
      activity, transcortical electroencephalographic (EEG) activity was recorded in
      conjunction with single- or dual-unit neuronal activity in the subthalamic
      nucleus (STN) or the globus pallidus (GP), and the data were analyzed with
      spectral and wavelet analyses. Multisecond oscillations in firing rates of 31% of
      the STN neurons and 46% of the GP neurons with periodicities significantly
      correlated with bursts of theta (4-7 Hz) activity in transcortical EEG. Further
      recordings of localized field potentials in the hippocampus and frontal or
      parietal cortices simultaneously with GP unit activity showed field potentials
      from the hippocampus, but not from the frontal or parietal cortices, exhibited
      bursts of theta rhythm that were correlated with GP firing rate oscillations.
      These results demonstrate a functional connectivity between basal ganglia
      neuronal activity and theta band activity in the hippocampus.

PMID- 11826076
TI  - Contrasting neuronal activity in the dorsal and ventral premotor areas during
      preparation to reach.
AB  - We compared neuronal activity in the dorsal and ventral premotor areas (PMd and
      PMv, respectively) when monkeys were preparing to perform arm-reaching movements
      in a motor-set period before their actual execution. They were required to select
      one of four possible movements (reaching to a target on the left or right, using
      either the left or right arm) in accordance with two sets of instruction cues,
      followed by a delay period, and a subsequent motor-set period. During the motor
      set period, the monkeys were required to get ready for a movement-trigger signal
      to start the arm-reach promptly. We analyzed the activity of 211 PMd and 109 PMv
      neurons that showed selectivity for the combination of the two instruction cues
      during the motor-set period. A majority (53%) of PMd neurons exhibited activity
      significantly tuned to both target location and arm use, and an approximately
      equal number of PMd neurons showed selectivity to either forthcoming arm use or
      target location. In contrast, 60% of PMv neurons showed selectivity for target
      location only and not for arm use. These findings point to preference in the use
      of neuronal activity in the two areas: preparation for action in the PMd and
      preparation for target acquisition in the PMv.

PMID- 11826077
TI  - Failure of averaging in the construction of a conductance-based neuron model.
AB  - Parameters for models of biological systems are often obtained by averaging over
      experimental results from a number of different preparations. To explore the
      validity of this procedure, we studied the behavior of a conductance-based model
      neuron with five voltage-dependent conductances. We randomly varied the maximal
      conductance of each of the active currents in the model and identified sets of
      maximal conductances that generate bursting neurons that fire a single action
      potential at the peak of a slow membrane potential depolarization. A model
      constructed using the means of the maximal conductances of this population is not
      itself a one-spike burster, but rather fires three action potentials per burst.
      Averaging fails because the maximal conductances of the population of one-spike
      bursters lie in a highly concave region of parameter space that does not contain
      its mean. This demonstrates that averages over multiple samples can fail to
      characterize a system whose behavior depends on interactions involving a number
      of highly variable components.

PMID- 11826079
TI  - Podokinetic after-rotation following unilateral and bilateral podokinetic
      stimulation.
AB  - Previous studies demonstrated an aftereffect of walking on a rotating treadmill,
      involving inadvertent circular navigation with eyes closed [podokinetic after
      rotation (PKAR)]. We compared PKAR following unilateral and bilateral podokinetic
      (PK) stimulation to determine whether the left and right legs could be
      independently adapted. Each subject performed two sessions of PK stimulation,
      stepping in place with one foot on either side of the axis of a rotating disk.
      Subjects experienced bilateral stimulation (i.e., both left and right feet
      stepped on the rotating disk) in one session and unilateral stimulation (i.e.,
      the left foot stepped on the rotating disk and the right foot stepped on a
      stationary surface) in the other. Following stimulation, we recorded foot lift
      off and touchdown times and pelvic angular velocity while subjects stepped in
      place on a stationary surface. PKAR velocity following unilateral stimulation was
      lower than that following bilateral stimulation. Following bilateral stimulation,
      pelvic rotation was in the counterclockwise (CCW) direction during single-limb
      support on both the left and right sides. Immediately following left unilateral
      stimulation, subjects demonstrated CCW pelvic rotation during left single-limb
      support but not during right single-limb support. Across the first 13 strides,
      the difference between left and right sides diminished; pelvic angular velocity
      was then CCW during single-limb support on both sides. This suggests that both
      the adapted left and the unadapted right limb influenced the final PKAR response
      with information from the two limbs being integrated over the first few strides.

PMID- 11826078
TI  - Calcium signaling at single mossy fiber presynaptic terminals in the rat
      hippocampus.
AB  - We investigated internal Ca(2+) release at mossy fiber synapses on CA3 pyramidal
      neurons (mossy fiber terminals, MFTs) in the hippocampus. Presynaptic Ca(2+)
      influx was induced by giving a brief train of 20 stimuli at 100 Hz to the mossy
      fiber pathway. Using Ca(2+) imaging techniques, we recorded the Ca(2+) response
      as DeltaF/F, which increased rapidly with stimulation, but was often accompanied
      by a delayed peak that occurred after the train. The rise in presynaptic [Ca(2+)]
      could be completely blocked by application of 400 microM Cd(2+). Furthermore, the
      evoked Ca(2+) signals were reduced by group II mGluR agonists. Under the same
      experimental conditions, we investigated the effects of several agents on MFTs
      that disrupt regulation of intracellular Ca(2+) stores resulting in depletion of
      internal Ca(2+). We found that ryanodine, cyclopiazonic acid, thapsigargin, and
      ruthenium red all decreased both the early and the delayed increase in the Ca(2+)
      signals. We applied D,L-2-amino-5-phosphonovaleric acid (D,L-APV; 50 microM) and
      6,7-Dinitroquinoxaline-2,3-dione (DNQX; 20 microM) to exclude the action of N
      methyl-D-aspartate (NMDA) and non-NMDA receptors. Experiments with alternative
      lower affinity indicators for Ca(2+) (fura-2FF and calcium green-2) and the
      transient K(+) channel blocker, 4-aminopyridine were performed to control for the
      possible saturation of fura-2. Taken together, these results strongly support the
      hypothesis that the recorded terminals were from the mossy fibers of the dentate
      gyrus and suggest that a portion of the presynaptic Ca(2+) signal in response to
      brief trains of stimuli is due to release of Ca(2+) from internal stores.

PMID- 11826080
TI  - Transfer of podokinetic adaptation from stepping to hopping.
AB  - Following stepping in-place on the surface of a rotating circular treadmill, a
      subject attempting to step in-place or walk in a straight line across the floor
      without vision will rotate relative to space. This adaptation, termed podokinetic
      after-rotation (PKAR), transfers to backward walking following forward walking on
      the rotating disk. We asked whether adaptation obtained during stepping in-place
      on the rotating disk would transfer to hopping on both feet. We hypothesized that
      subjects would demonstrate PKAR during both hopping and stepping, adding support
      to the hypothesis that PKAR is a centrally mediated adaptation of general
      locomotor trajectory that is not specific to the form of locomotion used while on
      the rotating disk. Subjects demonstrated PKAR during both hopping and stepping
      after stepping in-place on the rotating disk. The time courses of PKAR during
      hopping and stepping were similar, although the angular velocity amplitude of
      PKAR was lower in hopping than in stepping. This difference in amplitude suggests
      an incomplete transfer of PKAR.

PMID- 11826081
TI  - Slow oscillatory discharge in the primate basal ganglia.
AB  - Oscillations with periods in the multisecond range have previously been recorded
      in basal ganglia neurons of awake paralyzed rats, and in these animals were shown
      to be increased by systemic dopaminergic stimulation, but not altered by
      depletion of the nigrostriatal dopamine supply. To determine whether oscillations
      with frequencies below 0.5 Hz also exist in the primate basal ganglia, the
      spontaneous neuronal activity in the subthalamic nucleus (STN) and in the
      external and internal segments of the globus pallidus (GPe and GPi, respectively)
      was recorded with standard extracellular recording methods in two animals before
      and after treatment with the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP). Oscillations with mean periods around 80 s were
      identified in 30% percent of GPe neurons, 36% of STN neurons, and 48% of GPi
      neurons. After recording in the normal state, the animals were rendered
      parkinsonian by intracarotid application of MPTP. This treatment resulted in a
      30% reduction of the average discharge rate in GPe, a 47% increase of the average
      discharge rate in STN, and a 15% increase of the average discharge rate in GPi.
      However, there were no changes in the proportion of cells with slow oscillatory
      discharge. The oscillation frequencies were slightly increased in STN but
      remained unchanged in GPe and GPi. The results demonstrate that multisecond
      oscillations commonly occur in primate basal ganglia neurons and are unchanged by
      treatment with MPTP. The oscillations may have roles in fundamental functions of
      the basal ganglia-thalamocortical network, such as the regulation of the state of
      arousal.

PMID- 11826082
TI  - Simultaneous encoding of multiple potential reach directions in dorsal premotor
      cortex.
AB  - We present evidence that the primate brain can simultaneously generate discrete
      directional signals related to multiple alternative reaching actions before
      making a decision between them. A monkey performed a task in which the correct
      target for a reaching movement was specified during two consecutive instructed
      delay periods. First, two potential targets were presented; and second, a
      nonspatial cue identified one of them as the correct movement target. During the
      first period, two directional signals coexisted in the activity of cells in
      dorsal premotor cortex (PMd), oriented toward the two potential targets. During
      the second period, one of these disappeared and the remaining signal predicted
      the monkey's response choice. These results suggest that, when faced with
      multiple salient opportunities for reaching, the primate brain performs
      sensorimotor transformations in parallel to begin planning several reaching
      movements simultaneously before selecting one for overt execution.

PMID- 11826083
TI  - Modulation of somatodendritic dopamine release by endogenous H(2)O(2):
      susceptibility in substantia nigra but resistance in VTA.
AB  - We showed previously that dopamine (DA) release in dorsal striatum is inhibited
      by endogenously generated hydrogen peroxide (H(2)O(2)). Here, we examined whether
      endogenous H(2)O(2) can also modulate somatodendritic DA release in the
      substantia nigra pars compacta (SNc) and the ventral tegmental area (VTA), with
      companion measurements in DA terminal regions. Evoked DA release was monitored in
      brain slices using carbon-fiber microelectrodes with fast-scan cyclic
      voltammetry. Exogenous H(2)O(2) decreased DA release by 50-60% in SNc and VTA but
      only by 35% in nucleus accumbens. Whether endogenous H(2)O(2) also modulated
      somatodendritic release was examined using the glutathione peroxidase inhibitor,
      mercaptosuccinate (MCS), which should increase stimulation-evoked H(2)O(2)
      levels. In the presence of MCS, DA release was suppressed by 30-40% in SNc as
      well as in dorsal striatum and nucleus accumbens. In striking contrast, DA
      release in the VTA was unaffected by MCS. These data are consistent with stronger
      H(2)O(2) regulation or lower H(2)O(2) generation in VTA than in the other
      regions. Importantly, oxidative stress has been linked causally to Parkinson's
      disease, in which DA cells in SNc degenerate, but VTA cells are spared. The
      present data suggest that differences in oxidant regulation or generation between
      SNc and VTA could contribute to this.

PMID- 11826084
TI  - Horizontal vestibuloocular reflex (VOR) head velocity estimation in Purkinje cell
      degeneration (pcd/pcd) mutant mice.
AB  - The horizontal vestibuloocular reflex (VOR) of Purkinje cell degeneration
      (pcd/pcd) mutant mice, which lack a functional cerebellar cortex, was compared in
      darkness to that of wild-type animals during constant velocity yaw rotations
      about an earth-horizontal axis and during sinusoidal yaw rotations about an earth
      vertical axis. Both wild-type and pcd/pcd mice showed a compensatory average VOR
      eye velocity, or bias, during constant velocity horizontal axis rotations,
      evidence of central neural processing of otolith afferent signals to create a
      signal proportional to head angular velocity. Eye velocity bias was greater in
      pcd/pcd mice than in wild-type mice at a low rotational velocity (32 degrees/s),
      but less at higher velocities (128 and 200 degrees/s). Lesion of the medial
      nodulus severely attenuated eye velocity bias in two wild-type mice, without
      attenuating VOR during sinusoidal vertical axis yaw rotations at 0.2 Hz. These
      results show that while head velocity estimation in mice, as in primates, depends
      on the cerebellum, pcd/pcd mutant mice develop velocity estimation without a
      functional cerebellar cortex. We conclude that neural circuits that exclude
      cerebellar cortex are capable of the signal processing necessary for head angular
      velocity estimation, but that these circuits are insufficient for normal
      estimation at high velocities.

PMID- 11826085
TI  - Fast network oscillations in the rat dentate gyrus in vitro.
AB  - The dentate gyrus is a prominent source of gamma frequency activity in the
      hippocampal formation in vivo. Here we show that transient epochs of gamma
      frequency network activity (67 +/- 12 Hz) can be generated in the dentate gyrus
      of rat hippocampal slices, following brief pressure ejections of a high-molarity
      potassium solution onto the molecular layer. Oscillatory activity remains
      synchronized over distances >300 microm and is accompanied by a modest rise in
      [K(+)](o). Gamma frequency oscillations were abolished by a GABA(A) receptor
      antagonist demonstrating their dependence on rhythmic inhibition. However, in
      many cases, higher frequency oscillations (>80 Hz) remained in the absence of
      synaptic transmission, thus demonstrating that nonsynaptic factors may underlie
      fast oscillatory activity.

PMID- 11826086
TI  - Distance-dependent Ni(2+)-sensitivity of synaptic plasticity in apical dendrites
      of hippocampal CA1 pyramidal cells.
AB  - Low concentration of Ni(2+), a T- and R-type voltage-dependent calcium channel
      (VDCC) blocker, is known to inhibit the induction of long-term potentiation (LTP)
      in the hippocampal CA1 pyramidal cells. These VDCCs are distributed more
      abundantly at the distal area of the apical dendrite than at the proximal
      dendritic area or soma. Therefore we investigated the relationship between the
      Ni(2+)-sensitivity of LTP induction and the synaptic location along the apical
      dendrite. Field potential recordings revealed that 25 microM Ni(2+) hardly
      influenced LTP at the proximal dendritic area (50 microM distant from the
      somata). In contrast, the same concentration of Ni(2+) inhibited the LTP
      induction mildly at the middle dendritic area (150 microM) and strongly at the
      distal dendritic area (250 microM). Ni(2+) did not significantly affect either
      the synaptic transmission at the distal dendrite or the burst-firing ability at
      the soma. However, synaptically evoked population spikes recorded near the somata
      were slightly reduced by Ni(2+) application, probably owing to occlusion of
      dendritic excitatory postsynaptic potential (EPSP) amplification. Even when the
      stimulating intensity was strengthened sufficiently to overcome such a reduction
      in spike generation during LTP induction, the magnitude of distal LTP was not
      significantly recovered from the Ni(2+)-dependent inhibition. These results
      suggest that Ni(2+) may inhibit the induction of distal LTP directly by blocking
      calcium influx through T- and/or R-type VDCCs. The differentially distributed
      calcium channels may play a critical role in the induction of LTP at dendritic
      synapses of the hippocampal pyramidal cells.

PMID- 11826087
TI  - Neurogenesis in the adult brain.

PMID- 11826088
TI  - Adult neurogenesis in mammals: an identity crisis.

PMID- 11826089
TI  - Neurogenesis in adult mammals: some progress and problems.

PMID- 11826090
TI  - Why are some neurons replaced in adult brain?

PMID- 11826091
TI  - Neurogenesis in adult subventricular zone.

PMID- 11826092
TI  - Why new neurons? Possible functions for adult hippocampal neurogenesis.

PMID- 11826093
TI  - Neurogenesis in embryos and in adult neural stem cells.

PMID- 11826094
TI  - Specific gap junctions enhance the neuronal vulnerability to brain traumatic
      injury.
AB  - Traumatic brain injury results in neuronal loss and associated neurological
      deficits. Although most research on the factors leading to trauma-induced damage
      focuses on synaptic or ionic mechanisms, the possible role of direct
      intercellular communication via gap junctions has remained unexplored. Gap
      junctions connect directly the cytoplasms of coupled cells; hence, they offer a
      way to propagate stress signals from cell to cell. We investigated the
      contribution of gap junctional communication (GJC) to cell death using an in
      vitro trauma model. The impact injury, induced by a weight dropped on the distal
      CA1 area of organotypic hippocampal slices, results in glutamate-dependent cell
      loss. The gap junctional blockers carbenoxolone and octanol decreased
      significantly post-traumatic cell death, measured by propidium iodide staining
      over a 72 hr period after the impact. Dye coupling in the pyramidal layers was
      enhanced immediately after the injury and decreased over the following 24 hr. To
      determine whether specific connexins were involved in the spread of trauma
      induced cell death, we used organotypic slices from connexin43 (Cx43) knock-out
      mice, as well as acute knock-outs by incubation with antisense
      oligodeoxynucleotides. Simultaneous knockdown of two neuronal connexins resulted
      in significant neuroprotection. Slices from the null-mutant Cx43 mice, as well as
      the acute Cx43 knockdown, also showed decreased cell death after the impact. The
      gap junctional blockers alleviated the trauma-induced impairment of synaptic
      function as measured by electrophysiological field potential recordings. These
      results indicate that GJC enhances the cellular vulnerability to traumatic
      injury. Hence, specific gap junctions could be a novel target to reduce injury
      and secondary damage to the brain and maximize recovery from trauma.

PMID- 11826095
TI  - Development of vesicle pools during maturation of hippocampal synapses.
AB  - We studied the emergence of vesicle pool organization at developing hippocampal
      synapses by monitoring vesicle recycling and neurotransmitter release as well as
      examining electron micrographs. Our analysis suggests that presynaptic boutons go
      through three distinct functional states to mature. At the onset the synapses
      lack readily releasable vesicles although they possess a pool of recycling
      vesicles that can release neurotransmitters under strong stimulation. In the next
      stage the majority of these recycling vesicles switches to a functionally docked
      state and forms the readily releasable pool (RRP). After assembly of the RRP, new
      vesicles build the reserve pool. At the mature state the size of the RRP
      increases linearly with increasing recycling pool size. Furthermore, this
      preferential filling of the RRP during early synapse maturation is reduced
      strikingly in synapses deficient in synapsin I and II. Taken together, these
      results expose a mechanism that ensures functionally effective allocation of a
      limited number of vesicles in a CNS synapse.

PMID- 11826096
TI  - Functional specificity of G alpha q and G alpha 11 in the cholinergic and
      glutamatergic modulation of potassium currents and excitability in hippocampal
      neurons.
AB  - In hippocampal and other cortical neurons, action potentials are followed by a
      slow afterhyperpolarization (sAHP) generated by the activation of small
      conductance Ca(2+)-activated K(+) channels and controlling spike frequency
      adaptation. The corresponding current, the apamin-insensitive sI(AHP), is a well
      known target of modulation by different neurotransmitters, including
      acetylcholine (via M(3) receptors) and glutamate (via metabotropic glutamate
      receptor 5, mGluR(5)), in CA1 pyramidal neurons. The actions of muscarinic and
      mGluR agonists on sI(AHP) involve the activation of pertussis toxin-insensitive G
      proteins. However, the pharmacological tools available so far did not permit the
      identification of the specific G-protein subtypes transducing the effects of M(3)
      and mGluR(5) on sI(AHP). In the present study, we used mice deficient in the
      Galpha(q) and Galpha(11) genes to investigate the specific role of these G
      protein alpha subunits in the cholinergic and glutamatergic modulation of sI(AHP)
      in CA1 neurons. In mice lacking Galpha(q), the effects of muscarinic and
      glutamatergic agonists on sI(AHP) were nearly abolished, whereas beta-adrenergic
      agonists acting via Galpha(s) were still fully effective. Modulation of sI(AHP)
      by any of these agonists was instead unchanged in mice lacking Galpha(11). The
      additional depolarizing effects of muscarinic and glutamatergic agonists on CA1
      neurons were preserved in mice lacking Galpha(q) or Galpha(11). Thus, Galpha(q),
      but not Galpha(11), mediates specifically the action of cholinergic and
      glutamatergic agonists on sI(AHP), without affecting the modulation of other
      currents. These results provide to our knowledge one of the first examples of the
      functional specificity of Galpha(q) and Galpha(11) in central neurons.

PMID- 11826097
TI  - Potentiation of hippocampal synaptic transmission by superoxide requires the
      oxidative activation of protein kinase C.
AB  - Recent evidence suggests that reactive oxygen species (ROS), including
      superoxide, are not only neurotoxic but function as small messenger molecules in
      normal neuronal processes such as synaptic plasticity. Consistent with this idea,
      we show that brief incubation of hippocampal slices with the superoxide
      generating system xanthine/xanthine oxidase (X/XO) produces a long-lasting
      potentiation of synaptic transmission in area CA1. We found that X/XO-induced
      potentiation was associated with a persistent superoxide-dependent increase in
      autonomous PKC activity that could be isolated via DEAE column chromatography.
      The X/XO-induced potentiation was blocked by the inhibition of PKC, indicating
      that the superoxide-dependent increase in autonomous PKC activity was necessary
      for the potentiation. We also found that X/XO-induced potentiation and long-term
      potentiation (LTP) occluded one another, suggesting that these forms of
      plasticity share similar cellular mechanisms. In further support of this idea, we
      found that a persistent, superoxide-dependent increase in autonomous PKC activity
      isolated via DEAE column chromatography also was associated with LTP. Taken
      together, our findings indicate that X/XO-induced potentiation and LTP share
      similar cellular mechanisms, including superoxide-dependent increases in
      autonomous PKC activity. Finally, our findings suggest that superoxide, in
      addition to its well known role as a neurotoxin, also can be considered a small
      messenger molecule critical for normal neuronal signaling.

PMID- 11826098
TI  - GABAergic innervation organizes synaptic and extrasynaptic GABAA receptor
      clustering in cultured hippocampal neurons.
AB  - We have studied the effects of GABAergic innervation on the clustering of GABA(A)
      receptors (GABA(A)Rs) in cultured hippocampal neurons. In the absence of
      GABAergic innervation, pyramidal cells form small (0.36 +/- 0.01 micrometer
      diameter) GABA(A)R clusters at their surface in the dendrites and soma. When
      receiving GABAergic innervation from glutamic acid decarboxylase-containing
      interneurons, pyramidal cells form large (1.62 +/- 0.08 micrometer breadth)
      GABA(A)R clusters at GABAergic synapses. This is accompanied by a disappearance
      of the small GABA(A)R clusters in the local area surrounding each GABAergic
      synapse. Although the large synaptic GABA(A)R clusters of any neuron contained
      all GABA(A)R subunits and isoforms expressed by that neuron, the small clusters
      not localized at GABAergic synapses showed significant heterogeneity in subunit
      and isoform composition. Another difference between large GABAergic and small non
      GABAergic GABA(A)R clusters was that a significant proportion of the latter was
      juxtaposed to postsynaptic markers of glutamatergic synapses such as PSD-95 and
      AMPA receptor GluR1 subunit. The densities of both the glutamate receptor
      associated and non-associated small GABA(A)R clusters were decreased in areas
      surrounding GABAergic synapses. However, no effect on the density or distribution
      of glutamate receptor clusters was observed. The results suggest that there are
      local signals generated at GABAergic synapses that induce both assembly of large
      synaptic GABA(A)R clusters at the synapse and disappearance of the small GABA(A)R
      clusters in the surrounding area. In the absence of GABAergic innervation, weaker
      GABA(A)R-clustering signals, generated at glutamatergic synapses, induce the
      formation of small postsynaptic GABA(A)R clusters that remain juxtaposed to
      glutamate receptors at glutamatergic synapses.

PMID- 11826099
TI  - Process outgrowth of oligodendrocytes is promoted by interaction of fyn kinase
      with the cytoskeletal protein tau.
AB  - Fyn kinase plays an important role during myelination and has been shown to
      promote morphological differentiation of cultured oligodendrocytes. We analyzed
      the downstream targets of Fyn kinase in oligodendrocytes. Because process
      outgrowth and wrapping of axons involve cytoskeletal rearrangement, we focused on
      cytoskeletal proteins linked to Fyn. Here we demonstrate that Fyn binds to the
      cytoskeletal proteins Tau and alpha-Tubulin in oligodendrocytes. Tau interacts
      with the Fyn SH3 domain whereas alpha-Tubulin binds to the Fyn SH2 and SH3
      domains. To study the function of the Fyn-Tau interaction in oligodendrocytes, we
      designed a Tau deletion mutant that would compete with endogenous Tau-Fyn binding
      in transfected cells. The mutant Tau protein binds to the Fyn SH3 domain but
      lacks the microtubuli interaction domain and thus cannot bind to microtubuli. In
      the presence of the mutant Tau protein, a reduction of the process number and
      process length in oligodendroglial cells was observed. This effect is likely to
      be caused by interference with the Fyn-Tau-microtubuli cascade rather than
      inactivation of the kinase, because Fyn bound to the mutant Tau retains activity.
      A similar inhibition of process outgrowth was observed when oliogodendroglial
      cells were cultured in the presence of Fumonisin B1, an inhibitor of sphingolipid
      synthesis that prevents the formation of rafts. Because ligation of the cell
      adhesion molecule F3 on oligodendrocytes leads to activation of Fyn kinase
      localized in rafts, these findings suggest that recruitment of Tau and Tubulin to
      activated Fyn kinase in rafts is an important step in the initiation of
      myelination.

PMID- 11826100
TI  - The neuromuscular junctions of the slow and the fast excitatory axon in the
      closer of the crab Eriphia spinifrons are endowed with different Ca2+ channel
      types and allow neuron-specific modulation of transmitter release by two
      neuropeptides.
AB  - Most crustacean muscle fibers receive double excitatory innervation by
      functionally different motor neurons termed slow and fast. By using specific
      omega-toxins we show that the terminals of the slow closer excitor (SCE) and the
      fast closer excitor (FCE) at a crab muscle are endowed with different sets of
      presynaptic Ca(2+) channel types. omega-Agatoxin, a blocker of vertebrate P/Q
      type channels, reduced the amplitude of EPSCs by decreasing the mean quantal
      content of transmitter release in both neurons by 70-85%, depending on the
      concentration. We provide the first evidence that omega-conotoxin-sensitive
      channels also participate in transmission at crustacean neuromuscular terminals
      and are colocalized with omega-agatoxin-sensitive channels in an axon-type
      specific distribution. omega-Conotoxin, a blocker of vertebrate N-type channels,
      inhibited release by 20-25% only at FCE, not at SCE endings. Low concentrations
      of Ni(2+), which block vertebrate R-type channels, inhibited release in endings
      of the SCE by up to 35%, but had little effects in FCE endings. We found that two
      neuropeptides, the FMRFamide-like DF(2) and proctolin, which occur in many
      crustaceans, potentiated evoked transmitter release differentially. Proctolin
      increased release at SCE and FCE endings, and DF(2) increased release only at FCE
      endings. Selective blocking of Ca(2+) channels by different omega-toxins in the
      presence of peptides revealed that the target of proctolin-mediated modulation is
      the omega-agatoxin-sensitive channel (P/Q-like), that of DF(2) the omega
      conotoxin-sensitive channel (N-like). The differential effects of these two
      peptides allows fine tuning of transmitter release at two functionally different
      motor neurons innervating the same muscle.

PMID- 11826101
TI  - Antioscillatory effects of nociceptin/orphanin FQ in synaptic networks of the rat
      thalamus.
AB  - Postsynaptic and presynaptic effects of nociceptin/orphanin FQ (N/OFQ), the
      endogenous ligand of the opioid-like orphan receptor, were investigated in an in
      vitro slice preparation of the rat thalamic reticular nucleus (NRT) and
      ventrobasal complex (VB). In NRT as well as VB, all tested neurons developed an
      outward current on application of 1 micrometer N/OFQ. Basic properties of the
      N/OFQ-induced current included inward rectification, dependence on extracellular
      K(+), reduction by 100 micrometer Ba(+), antagonistic effect of
      [Nphe(1)]nociceptin(1-13)NH(2), and sensitivity to internal GDP-beta-S. Miniature
      IPSCs (mIPSCs) mediated by GABA(A) receptors in VB neurons were not affected by 1
      micrometer N/OFQ. In addition, paired-pulse depression of evoked IPSCs was
      unchanged, indicating a lack of presynaptic effects. By comparison, N/OFQ
      application resulted in a reduction in frequency of miniature EPSCs (mEPSCs) in a
      subpopulation of NRT neurons, whereas paired-pulse facilitation of evoked EPSCs
      was not altered. In either nucleus, current-clamp experiments revealed a
      hyperpolarization and associated decrease in input resistance in response to
      N/OFQ. Although N/OFQ had no measurable effect on calcium-mediated burst activity
      evoked by depolarizing steps from hyperpolarized values of the membrane
      potential, rebound bursts on relief of hyperpolarizing current steps were
      decreased. Slow thalamic oscillations induced in vitro by extracellular
      stimulation were dampened by N/OFQ in VB and NRT, as seen by delayed onset of
      rhythmic multiple-unit activity and reduction in amplitude and duration. We
      conclude that N/OFQ reduces the excitability of NRT and VB neurons predominantly
      through an increase of a G-protein-coupled inwardly rectifying K(+) conductance.

PMID- 11826102
TI  - Separation of presynaptic and postsynaptic contributions to depression by
      covariance analysis of successive EPSCs at the calyx of Held synapse.
AB  - Synaptic short-term plasticity is considered to result from multiple cellular
      mechanisms, which may include presynaptic and postsynaptic contributions. We have
      recently developed a nonstationary EPSC fluctuation analysis (Scheuss and Neher,
      2001) to estimate synaptic parameters and their transient changes during short
      term synaptic plasticity. Extending the classical variance-mean approach, a short
      train of stimuli is applied repetitively, and the resulting EPSCs are analyzed
      for means, variances, and covariances. This provides estimates of the quantal
      size and quantal content for each EPSC in the train, and furthermore, an estimate
      of the number of release sites. The latter is less sensitive to heterogeneity in
      the release probability than that of the variance-mean approach. Here, we applied
      this analysis to the calyx of Held synapse in brainstem slices of young rats
      (postnatal day 8-10). We found significant negative covariance in the amplitude
      of successive EPSCs in a train. The analysis showed that the 10-fold depression
      in the EPSC amplitude during 100 Hz trains at elevated extracellular Ca(2+)
      concentration resulted from a 2.5-fold reduction in quantal size caused by
      postsynaptic AMPA receptor desensitization and saturation, and a fourfold
      reduction in quantal content, which was partially relieved by application of
      cyclothiazide. The number of release sites estimated by covariance analysis was
      approximately 2000 and significantly larger than estimates from variance-mean
      parabolas.

PMID- 11826103
TI  - Cell type- and subcellular position-dependent summation of unitary postsynaptic
      potentials in neocortical neurons.
AB  - Theoretical studies predict that the modes of integration of coincident inputs
      depend on their location and timing. To test these models experimentally, we
      simultaneously recorded from three neocortical neurons in vitro and investigated
      the effect of the subcellular position of two convergent inputs on the response
      summation in the common postsynaptic cell. When scattered over the
      somatodendritic surface, combination of two coincident excitatory or inhibitory
      synaptic potentials summed linearly in layer 2/3 pyramidal cells, as well as in
      GABAergic interneurons. Slightly sublinear summation with connection specific
      kinetics was observed when convergent inputs targeted closely placed sites on the
      postsynaptic cell. The degree of linearity of summation also depended on the type
      of connection, the relative timing of inputs, and the activation state of I(h).
      The results suggest that, when few inputs are active, the majority of afferent
      permutations undergo linear integration, maintaining the importance of individual
      inputs. However, compartment- and connection-specific nonlinear interactions
      between synapses located close to each other could increase the computational
      power of individual neurons in a cell type-specific manner.

PMID- 11826104
TI  - Ultrastructure of a somatic spine mat for nicotinic signaling in neurons.
AB  - Chick ciliary neurons have somatic spines grouped in discrete clumps or mats
      tightly folded against the soma and enriched in nicotinic receptors containing
      alpha7 subunits. An embryonic ciliary neuron has one to two dozen such spine
      mats, all overlaid by a large presynaptic calyx engulfing the cell. Three
      dimensional tomographic reconstruction from serial thick sections revealed 13
      somatic spines in one complete spine mat on a ciliary neuron late in
      embryogenesis. The spines varied in morphology and usually were branched but had
      numerous similarities to dendritic spines, including mean length, volume, surface
      area, presence of endoplasmic reticulum, and occasional multivesicular bodies.
      The spines invariably were connected to the soma via a narrow neck of
      approximately 0.2 micrometer in diameter as found for dendritic spines,
      suggesting restricted access from spine lumen to soma. A prominent difference
      between dendritic and somatic spines is the absence of postsynaptic densities
      from most somatic spines both on embryonic and adult ciliary neurons. Transmitter
      access to receptors on the spines may occur either by lateral diffusion from
      release sites over nearby postsynaptic densities or by release directly onto
      spines from the overlying calyx lined with vesicles. The latter is less likely in
      the adult, where some spines are adjacent to but not overlaid by vesicle-enriched
      presynaptic structures. The anatomical configuration of spine mats suggests
      coordinate spine activation by transmitter release into a confined volume while
      spine morphology is used to control the chemical consequences of synaptic
      signaling.

PMID- 11826105
TI  - Interaction of synaptic scaffolding molecule and Beta -catenin.
AB  - Synaptic scaffolding molecule (S-SCAM) is a synaptic membrane-associated
      guanylate kinase with inverted domain organization (MAGI) that interacts with
      NMDA receptor subunits and neuroligin. In epithelial cells, the non-neuronal
      isoform of S-SCAM (MAGI-1) is localized at tight or adherens junctions. Recent
      studies have revealed that the polarized targeting of MAGI-1 to the lateral
      membrane is mediated by its C-terminal region and that MAGI-1 interacts with beta
      catenin in epithelial cells. In this article, we report that S-SCAM interacts
      with beta-catenin in neurons. beta-Catenin is coimmunoprecipitated with S-SCAM
      from rat brain. Both S-SCAM and beta-catenin are localized at synapses and are
      partially colocalized. The C-terminal region of S-SCAM binds to the C-terminal
      region of beta-catenin. We have tested how the interaction between S-SCAM and
      beta-catenin plays a role in the synaptic targeting of S-SCAM and beta-catenin. S
      SCAM is targeted to synapses via the C-terminal postsynaptic density-95/Dlg-A/ZO
      1 (PDZ) domain. beta-Catenin is targeted to synapses with armadillo repeats. The
      overexpressed C-terminal region of beta-catenin blocks the synaptic targeting of
      S-SCAM. The overexpressed C-terminal region of S-SCAM is partially targeted to
      synapses and forms a small number of clusters. In the presence of overexpressed
      beta-catenin, the C-terminal region of S-SCAM forms more clusters at synapses.
      These data suggest that the synaptic targeting of S-SCAM is mediated by the
      interaction with beta-catenin.

PMID- 11826106
TI  - Novel microglomerular structures in the olfactory bulb of mice.
AB  - The murine olfactory system consists of two primary divisions: (1) a main
      olfactory system, in which olfactory sensory neurons (OSNs) located in the main
      olfactory epithelium (MOE) send their axons to glomeruli in the main olfactory
      bulb (MOB); and (2) an accessory olfactory system, in which OSNs located in the
      vomeronasal organ send their axons to glomeruli in the accessory olfactory bulb
      (AOB). In labeling studies using the lectin Ulex europaeus agglutinin (UEA), we
      discovered a novel subset of small neuropilar structures in the MOB that are
      distinct from other glomeruli both in the MOB and AOB. These "microglomeruli" are
      morphologically similar to MOB glomeruli in many respects: they receive
      innervation from processes present in the olfactory nerve layer and are isolated
      from other glomeruli by juxtaglomerular cells; in addition, the compartmental
      pattern of UEA labeling suggests the presence of UEA (-) processes within their
      neuropil. Microglomeruli contained processes that express the olfactory marker
      protein, a marker common to mature OSN axons. However, unlike other glomerular
      structures, the microglomeruli did not contain neural cell adhesion molecule
      labeled processes. Within microglomeruli, UEA(+) processes interdigitated with
      MAP2(+) dendrites, some of which likely originate from interneurons, as indicated
      by glutamic acid decarboxylase labeling. Synaptophysin labeling in microglomeruli
      strongly suggested that synapses occur between UEA(+) processes and dendrites.
      Anterograde labeling of OSNs, by injection of rhodamine-dextran into one naris,
      demonstrated that UEA(+) processes in microglomeruli originated in the MOE. The
      unique morphology, protein expression, and location of microglomeruli have led us
      to hypothesize that they represent a novel class of glomerular structures in the
      murine olfactory system.

PMID- 11826107
TI  - Stability and plasticity of developing synapses in hippocampal neuronal cultures.
AB  - To explore mechanisms governing the formation, stability, and elimination of
      synapses during neuronal development, we used FM 1-43 fluorescence imaging to
      track vesicle turnover at >7000 individually identified developing synapses
      between embryonic rat hippocampal neurons in culture. The majority of presynaptic
      boutons were stable in efficacy and position over a period of 1.5 hr. Activity,
      evoked by burst-patterned field stimulation, decreased presynaptic function
      across the population of boutons, an effect that required NMDA receptor
      activation. Decreased FM 1-43 staining correlated with low synapsin-I and
      synaptophysin immunoreactivities, suggesting that decreased presynaptic function
      was commensurate with synaptic disassembly. These observations provide new
      information on the stability of developing presynaptic function and suggest that
      NMDA receptor activation may regulate the stability of developing synapses.

PMID- 11826108
TI  - Distinct role for microglia in rotenone-induced degeneration of dopaminergic
      neurons.
AB  - Increasing evidence has suggested an important role for environmental factors
      such as exposure to pesticides in the pathogenesis of Parkinson's disease. In
      experimental animals the exposure to a common herbicide, rotenone, induces
      features of parkinsonism; mechanistically, rotenone-induced destruction of
      dopaminergic neurons has been attributed to its inhibition of the activity of
      neuronal mitochondrial complex I. However, the role of microglia, the resident
      brain immune cells in rotenone-induced neurodegeneration, has not been reported.
      Using primary neuron-enriched and neuron/glia cultures from the rat
      mesencephalon, we discovered an extraordinary feature for rotenone-induced
      degeneration of cultured dopaminergic neurons. Although little neurotoxicity was
      detected in neuron-enriched cultures after treatment for 8 d with up to 20 nm
      rotenone, significant and selective dopaminergic neurodegeneration was observed
      in neuron/glia cultures 2 d after treatment with 20 nm rotenone or 8 d after
      treatment with 1 nm rotenone. The greatly enhanced neurodegenerative ability of
      rotenone was attributed to the presence of glia, especially microglia, because
      the addition of microglia to neuron-enriched cultures markedly increased their
      susceptibility to rotenone. Mechanistically, rotenone stimulated the release of
      superoxide from microglia that was attenuated by inhibitors of NADPH oxidase.
      Furthermore, inhibition of NADPH oxidase or scavenging of superoxide
      significantly reduced the rotenone-induced neurotoxicity. This is the first
      report demonstrating that microglia play a pivotal role in rotenone-induced
      degeneration of dopaminergic neurons. The results of this study should advance
      our understanding of the mechanism of action for pesticides in the pathogenesis
      of Parkinson's disease.

PMID- 11826109
TI  - Traumatically induced axotomy adjacent to the soma does not result in acute
      neuronal death.
AB  - Traumatic axonal injury (TAI), a consequence of traumatic brain injury (TBI),
      results from progressive pathologic processes initiated at the time of injury.
      Studies attempting to characterize the pathology associated with TAI have not
      succeeded in following damaged and/or disconnected axonal segments back to their
      individual neuronal somata to determine their fate. To address this issue, 71
      adult male Sprague Dawley rats were subjected to moderate central fluid
      percussion injury and killed between 30 min and 7 d after injury. Antibodies to
      the C terminus of beta-amyloid precursor protein (APP) identified TAI in
      continuity with individual neuronal somata in the mediodorsal neocortex, the
      hilus of the dentate gyrus, and the dorsolateral thalamus. These somata were
      followed with immunocytochemical markers of neuronal injury targeting
      phosphorylated 200 kDa neurofilaments (RMO-24), altered protein translation
      (phosphorylated eukaryotic translation initiation factor 2 alpha), and cell death
      [terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)],
      with parallel electron microscopic (EM) assessment. Despite the finding of TAI
      within 20-50 micrometer of the soma, no evidence of cell death, long associated
      with proximal axotomy, was seen via TUNEL or routine light microscopy/electron
      microscopy. Rather, there was rapid onset (<6 hr after injury) subcellular change
      associated with impaired protein synthesis identified by EM, immunocytochemical,
      and Western blot analyses. When followed 7 d after injury, these abnormalities
      did not reveal dramatic progression. Rather, some somata showed evidence of
      potential reorganization and repair. This study demonstrates a novel somatic
      response to TAI in the perisomatic domain and also provides insight into the
      multifaceted pathology associated with TBI.

PMID- 11826110
TI  - Delphilin: a novel PDZ and formin homology domain-containing protein that
      synaptically colocalizes and interacts with glutamate receptor delta 2 subunit.
AB  - The glutamate receptor delta2 (GluRdelta2) subunit is selectively expressed in
      cerebellar Purkinje cells and plays an important role in cerebellar long-term
      depression, motor learning, motor coordination, and synapse development. We
      identified a novel GluRdelta2-interacting protein, named Delphilin, that contains
      a single PDZ domain and formin homology (FH) domains FH1 and FH2 plus coiled-coil
      structure. As far as we know, this is the first reported protein that contains
      both PDZ and FH domains. Yeast two-hybrid and surface plasmon resonance (SPR)
      analyses indicated that Delphilin interacts with the GluRdelta2 C terminus via
      its PDZ domain. This was also supported by coimmunoprecipitation experiments
      using a heterologous expression system in mammalian cells. Yeast cell and SPR
      analyses also demonstrated the possibility that the FH1 proline-rich region of
      Delphilin interacts with profilin, an actin-binding protein, and with the Src
      homology 3 domain of neuronal Src protein tyrosine kinase. In situ hybridization
      demonstrated the highest expression of Delphilin mRNA in Purkinje cells.
      Delphilin polypeptide was highly enriched in the synaptosomal membrane fraction
      of the cerebellum and coimmunoprecipitated with the GluRdelta2 subunit. The post
      embedding immunogold technique demonstrated that Delphilin is selectively
      localized at the postsynaptic junction site of the parallel fiber-Purkinje cell
      synapse and colocalized with GluRdelta2. Thus, Delphilin is a postsynaptic
      scaffolding protein at the parallel fiber-Purkinje cell synapse, where it may
      serve to link GluRdelta2 with actin cytoskeleton and various signaling molecules.

PMID- 11826111
TI  - N-myc promotes survival and induces S-phase entry of postmitotic sympathetic
      neurons.
AB  - In most postmitotic neurons, expression or activation of proteins that stimulate
      cell cycle progression or DNA replication results in apoptosis. One potential
      exception to this generalization is neuroblastoma (NB), a tumor derived from the
      sympathoadrenal lineage. NBs often express high levels of N-myc, a proto-oncogene
      that can potently activate key components of the cell cycle machinery. Here, we
      show that in postmitotic sympathetic neurons, N-myc can induce S-phase entry
      while protecting neurons from death caused by aberrant cell cycle reentry.
      Specifically, these experiments demonstrate that expression of N-myc at levels
      similar to those in NBs caused sympathetic neurons to reenter S-phase, as
      monitored by 5-bromo-2-deoxyuridine incorporation and expression of cell cycle
      regulatory proteins, and rescued them from apoptosis induced by withdrawal of
      their obligate survival factor, nerve growth factor. The N-myc-induced cell cycle
      entry, but not enhanced survival, was inhibited by coexpression of a
      constitutively hypophosphorylated form of the retinoblastoma tumor suppressor
      protein, suggesting that these two effects of N-myc are mediated by separate
      pathways. In contrast, N-myc did not cause S-phase entry in postmitotic cortical
      neurons. Thus, N-myc both selectively causes sympathetic neurons to reenter the
      cell cycle and protects them from apoptosis, potentially contributing to their
      transformation to NBs.

PMID- 11826112
TI  - Experience affects recruitment of new neurons but not adult neuron number.
AB  - It is not known whether the addition of new neurons to the high vocal center
      (HVC) of juvenile zebra finches permits vocal learning or is the consequence of
      it. To tease apart these two, we performed surgery on 26-d-old juveniles. The
      operations were removal of both cochleae and unilateral or bilateral denervation
      of the syrinx. Ability to imitate a tutor song was little affected by unilateral
      syringeal denervation but was severely hindered by bilateral denervation or
      deafening. Recruitment of new HVC neurons was studied by injecting BrdU, a cell
      birth marker, on post-hatching days 61-65 and killing the animals 30 d later.
      Deafening or bilateral denervation did not alter the number of BrdU-labeled
      neurons in HVC, but unilateral denervation nearly doubled this number in the
      intact side. This doubling was transient, was blocked by deafening, and was not
      seen in birds that received BrdU injections earlier or later in vocal ontogeny.
      The adult number of HVC neurons was not affected by any of our surgical
      procedures. Apparently experience does not affect the total number of neurons in
      adult HVC, but some kinds of experience can, during narrowly defined times,
      influence the recruitment of new HVC neurons.

PMID- 11826113
TI  - Persistent engrailed expression is required to determine sensory axon trajectory,
      branching, and target choice.
AB  - The transcription factor Engrailed (En) directs, in the cockroach cercal system,
      the shape of the axonal arborization and the choice of postsynaptic partners of
      an identified sensory neuron (6m). Knock-out of En using double-stranded RNA
      interference transforms 6m so that it resembles a neighboring neuron that
      normally does not express the en gene, has a different arbor anatomy, and makes
      different connections. We characterized the development of 6m and perturbed en
      expression at different stages. Our results show that En is not required before
      birth for 6m to become a neuron, but that it is required in the postmitotic
      neuron to control axonal arborization and synaptic specificity. Knock-out of En
      after 6m has entered the CNS does not change the axonal trajectory and has minor
      effects on axonal branches but causes the formation of synaptic connections
      typical of an En-negative cell. This suggests that En controls target recognition
      molecules independently from those guiding the axon. In contrast, double-stranded
      RNA injection 1 d later does not have any effects on the phenotype of 6m,
      suggesting that the period of synapse formation is over by the time En levels
      have fallen or, if synapse turnover occurs, that En is not required to maintain
      the specificity of synaptic connections. We conclude that persistent en
      expression is required to determine successive stages in the differentiation of
      the neuron, suggesting that it is not far upstream from those genes encoding axon
      guidance and synaptic recognition molecules.

PMID- 11826114
TI  - Repellent guidance of regenerating optic axons by chondroitin sulfate
      glycosaminoglycans in zebrafish.
AB  - We analyzed the role of chondroitin sulfate (CS) glycosaminoglycans, putative
      inhibitors of axonal regeneration in mammals, in the regenerating visual pathway
      of adult zebrafish. In the adult, CS immunoreactivity was not detectable before
      or after an optic nerve crush in the optic nerve and tract but was constitutively
      present in developing and adult nonretinorecipient pretectal brain nuclei, where
      CSs may form a boundary preventing regenerating optic fibers from growing into
      these inappropriate locations. Enzymatic removal of CSs by chondroitinase ABC
      after optic nerve crush significantly increased the number of animals showing
      erroneous growth of optic axons into the nonretinorecipient magnocellular
      superficial/posterior pretectal nucleus (83% vs 42% in controls). In vitro, a
      substrate border of CSs, but not heparan sulfates, strongly repelled regenerating
      retinal axons from adult zebrafish. We conclude that CSs contribute to repellent
      axon guidance during regeneration of the optic projection in zebrafish.

PMID- 11826115
TI  - Tumor necrosis factor inhibits neurite outgrowth and branching of hippocampal
      neurons by a rho-dependent mechanism.
AB  - In response to injury and inflammation of the CNS, brain cells including
      microglia and astrocytes secrete tumor necrosis factor-alpha (TNF). This pro
      inflammatory cytokine has been implicated in both neuronal cell death and
      survival. We now provide evidence that TNF affects the formation of neurites.
      Neurons cultured on astrocytic glial cells exhibited reduced outgrowth and
      branching of neurites after addition of recombinant TNF or prestimulation of
      glial cells to secrete TNF. This effect was absent in neurons of TNF receptor
      deficient mice cultured on prestimulated glia of wild-type mice and was reverted
      by blocking TNF with soluble TNF receptor IgG fusion protein. TNF activated in
      neurons the small GTPase RhoA. By inactivating Rho with C3 transferase, the
      inhibitory effect of TNF on neurite outgrowth and branching was abolished. These
      results suggest that glia-derived TNF, as part of an injury or inflammatory
      process, can inhibit neurite elongation and branching during development and
      regeneration.

PMID- 11826116
TI  - Fibroblast growth factor 2 is necessary for the growth of glutamate projection
      neurons in the anterior neocortex.
AB  - Basic fibroblast growth factor (Fgf2) is required for the generation of founder
      cells within the dorsal pseudostratified ventricular epithelium, which will
      generate the cerebral cortex, but the ganglionic eminences are not affected. We
      report here that the Fgf2 null mutant mice show an approximately 40% decrease in
      cortical glutamatergic pyramidal neurons. In contrast, no change in pyramidal or
      granule cell number is detected in the hippocampus of Fgf2 -/- mice. In addition,
      the soma of the pyramidal cells in the frontal and parietal cortices are smaller
      in Fgf2 knock-out mice. The decrease in the number and size of glutamatergic
      neuronal population affects all cortical layers but is restricted to the frontal
      and parietal cortices without any change in the occipital cortex, indicating that
      Fgf2 is necessary to regulate cell number and size in the anterior cerebral
      cortex. In contrast to pyramidal neurons, cortical GABA interneurons are
      unaffected by the lack of Fgf2. The resulting imbalance between the excitatory
      and inhibitory neurotransmission in the cerebral cortex is reflected by an
      increased duration of sleep when the animals receive a GABA receptor agonist.
      Thus, Fgf2 signaling may contribute to the regional specification of the cerebral
      cortex and may play a role in increasing the size of anterior cortical regions
      during vertebrate evolution.

PMID- 11826117
TI  - Proteolipid promoter activity distinguishes two populations of NG2-positive cells
      throughout neonatal cortical development.
AB  - Transgenic mice expressing enhanced green fluorescent protein (EGFP) driven by
      the mouse myelin proteolipid protein (PLP) gene promoter have been developed to
      investigate cells in the oligodendrocyte lineage. Transgene expression is
      consistent with the developmental expression of PLP, with cells at all stages of
      oligodendrocyte differentiation clearly visualized. These animals were analyzed
      to establish the time course of oligodendrocyte progenitor migration,
      proliferation, and differentiation in neonatal cortex. In these animals, two
      populations of NG2 proteoglycan-positive oligodendrocyte progenitor cells were
      identified that exist in postnatal subventricular zone and cortex. These two
      populations are distinguished by the presence or absence of PLP gene expression.
      Thus, PLP gene expression defines a subpopulation of NG2-positive cells from very
      early postnatal ages, which migrates toward the pial surface and proliferates in
      situ. EGFP(+)/NG2(+) cells are present in the cortex from postnatal day 1, and
      they remain in the cortex as undifferentiated oligodendrocyte progenitors for up
      to 3 weeks before myelination begins. These data could be explained by the
      presence of an important inhibitor of oligodendrocyte differentiation in the
      cortex during this period, which is downregulated in a region-specific manner to
      allow myelination. On the other hand, it is possible that oligodendrocyte
      progenitor cells remain undifferentiated in cortex until an essential signal is
      produced in situ to induce differentiation.

PMID- 11826118
TI  - Activity-dependent presynaptic effect of serotonin 1B receptors on the
      somatosensory thalamocortical transmission in neonatal mice.
AB  - The disruptive effect of excessive serotonin (5-HT) levels on the development of
      cortical sensory maps is mediated by 5-HT1B receptors, as shown in barrelless
      monoamine oxidase A knock-out mice, in which the additional inactivation of 5
      HT1B receptors restores the barrels. However, it is unclear whether 5-HT1B
      receptors mediate their effect on barrel formation by a trophic action or an
      activity-dependent effect. To test for a possible effect of 5-HT1B receptors on
      activity, we studied the influence of 5-HT on the thalamocortical (TC) synaptic
      transmission in layer IV cortical neurons. In TC slices of postnatal day 5 (P5)
      P9 neonate mice, we show that 5-HT reduces monosynaptic TC EPSCs evoked by low
      frequency internal capsule stimulation and relieves the short-term depression of
      the EPSC evoked by high-frequency stimulation. We provide evidence that 5-HT
      decreases the presynaptic release of glutamate: 5-HT reduces similarly the AMPA
      kainate and NMDA components and the paired pulse depression of TC EPSCs. We show
      also that 5-HT1B receptors mediate exclusively the effect of 5-HT: first, the
      effect of 5-HT on the TC EPSC is correlated with the transient expression of 5
      HT1B receptor mRNAs in the ventrobasal thalamic nucleus during postnatal
      development; second, it is mimicked by a 5-HT1B agonist; third, 5-HT has no
      effect in 5-HT1B receptor knock-out mice. Our results show that in the developing
      barrel field of the neonatal mice, 5-HT1B receptors mediate an activity-dependent
      regulation of the TC EPSC that could favor the propagation of high-frequency TC
      activity.

PMID- 11826119
TI  - Development of individual axon arbors in a thalamocortical circuit necessary for
      song learning in zebra finches.
AB  - Individual axon arbors within developing neural circuits are remodeled during
      restricted sensitive periods, leading to the emergence of precise patterns of
      connectivity and specialized adaptive behaviors. In male zebra finches, the
      circuit connecting the medial dorsolateral nucleus of the thalamus (DLM) and its
      cortical target, the lateral magnocellular nucleus of the anterior neostriatum
      (lMAN), is crucial for the acquisition of a normal vocal pattern during the
      sensitive period for song learning. The shell subregion of lMAN as well as the
      entire terminal field of DLM axons within lMAN undergo a striking increase in
      overall volume during early stages of vocal learning followed by an equally
      substantial decrease by adulthood, by which time birds have acquired stable song
      patterns. Because the total number of DLM neurons remains stable throughout this
      period, the dramatic changes within the overall DLM-->lMAN circuit are presumably
      attributable to dynamic rearrangements at the level of individual DLM axon arbors
      over the course of vocal learning. To study such rearrangements directly, we
      reconstructed individual DLM axon arbors in three dimensions at different stages
      during vocal learning. Unlike axon arbors in other model systems, in which the
      number of branches increases during development, DLM arbors are unusual in that
      they have the greatest number of branches at the onset of vocal learning and
      undergo large-scale retraction during the sensitive period for song learning.
      Decreases in the degree of overlap between DLM arbors apparently contribute to
      the increased overall volume of the DLM-->lMAN circuit during vocal learning.
      These developmental changes in DLM axon arbors occur at the height of the
      sensitive period for vocal learning, and hence may represent either a
      morphological correlate of song learning or a necessary prerequisite for
      acquisition of song.

PMID- 11826120
TI  - Expression of the nerve growth factor receptors TrkA and p75NTR in the visual
      cortex of the rat: development and regulation by the cholinergic input.
AB  - Several lines of evidence have shown that nerve growth factor (NGF), the
      progenitor of the neurotrophin family of growth factors, plays a fundamental role
      in the developmental plasticity of the rat visual cortex. However, the expression
      of NGF receptors (NGFRs) TrkA and p75(NTR) and the possible sites of NGF action
      in the visual cortex remain to be elucidated so far. Using a highly sensitive ECL
      immunoblot analysis, we have been able to show, in the present study, that the
      TrkA protein is expressed in the rat visual cortex and that it is developmentally
      upregulated during the critical period for cortical plasticity. In contrast, the
      expression level of the low-affinity NGF receptor p75(NTR) seems to remain nearly
      constant throughout development. In the analysis of possible pathways involved in
      the regulation of NGFR expression, we found that neither blockade of the visual
      input nor NGF administration to the visual cortex resulted in a modulation of
      NGFR levels of expression. On the other hand, the selective destruction of
      cholinergic afferents to the visual cortex caused a dramatic, but not complete,
      reduction of the cortical NGFRs, which suggests that these receptors are located
      on cholinergic terminals predominantly. At the functional level, we found that,
      after the elimination of the cholinergic afferents to the visual cortex, the NGF
      induced increase of both acetylcholine and glutamate release from cortical
      synaptosomes was strongly impaired. These results indicate that the cholinergic
      input is an important mediator of visual cortex responsiveness to NGF action.

PMID- 11826121
TI  - Matrix metalloproteinase-9 undergoes expression and activation during dendritic
      remodeling in adult hippocampus.
AB  - Neurons of adult brain are able to remodel their synaptic connections in response
      to various stimuli. Modifications of the peridendritic environment, including the
      extracellular matrix, are likely to play a role during synapse remodeling.
      Proteolytic disassembly of ECM is a complex process using the regulated actions
      of specific extracellular proteinases. One of best-characterized families of
      matrix-modifying enzymes is the matrix metalloproteinase (MMP) family. Here, we
      describe changes in the expression and function of two well known MMPs, MMP-9 and
      MMP-2, in adult rat brain before and after systemic administration of the
      glutamate receptor agonist kainate. Kainate application results in enhanced
      synaptic transmission and seizures followed by selective tissue remodeling,
      primarily in hippocampal dentate gyrus. MMP-9 but not MMP-2 was highly expressed
      by neurons in normal adult rat brain. MMP-9 protein was localized in neuronal
      cell bodies and dendrites. Kainate upregulated the level of MMP-9 mRNA and
      protein within hours after drug administration. This was followed several hours
      later by MMP-9 enzymatic activation. Within hippocampus, MMP-9 mRNA and activity
      were increased selectively in dentate gyrus, including its dendritic layer. In
      addition, MMP-9 mRNA levels decreased in areas undergoing neuronal cell loss.
      This unique spatiotemporal pattern of MMP-9 expression suggests its involvement
      in activity-dependent remodeling of dendritic architecture with possible effects
      on synaptic physiology.

PMID- 11826123
TI  - The role of auditory experience in the formation of neural circuits underlying
      vocal learning in zebra finches.
AB  - The initial establishment of topographic mapping within developing neural
      circuits is thought to be shaped by innate mechanisms and is primarily
      independent of experience. Additional refinement within topographic maps leads to
      precise matching between presynaptic and postsynaptic neurons and is thought to
      depend on experiential factors during specific sensitive periods in the animal's
      development. In male zebra finches, axonal projections of the cortical lateral
      magnocellular nucleus of the anterior neostriatum (lMAN) are critically important
      for vocal learning. Overall patterns of topographic organization in the majority
      of these circuits are adult-like throughout the sensitive period for vocal
      learning and remain stable despite large-scale functional and morphological
      changes. However, topographic organization within the projection from the core
      subregion of lMAN (lMAN(core)) to the motor cortical robust nucleus of the
      archistriatum (RA) is lacking at the onset of song development and emerges during
      the early stages of vocal learning. To study the effects of song-related
      experience on patterns of axonal connectivity within different song-control
      circuits, we disrupted song learning by deafening juvenile zebra finches or
      exposing them to loud white noise throughout the sensitive period for song
      learning. Depriving juvenile birds of normal auditory experience delayed the
      emergence of topographic specificity within the lMAN(core)-->RA circuit relative
      to age-matched controls, whereas topographic organization within all other
      projections to and from lMAN was not affected. The projection from lMAN(core) to
      RA therefore provides an unusual example of experience-dependent modification of
      large-scale patterns of brain circuitry, in the sense that auditory deprivation
      influences the development of overall topographic organization in this pathway.

PMID- 11826122
TI  - Mechanisms of the release of anterogradely transported neurotrophin-3 from axon
      terminals.
AB  - Neurotrophins have profound effects on synaptic function and structure. They can
      be derived from presynaptic, as well as postsynaptic, sites. To date, it has not
      been possible to measure the release of neurotrophins from axon terminals in
      intact tissue. We implemented a novel, extremely sensitive assay for the release
      and transfer of anterogradely transported neurotrophin-3 (NT-3) from a
      presynaptic to a postsynaptic location that uses synaptosomal fractionation after
      introduction of radiolabeled NT-3 into the retinotectal projection of chick
      embryos. Release of the anterogradely transported NT-3 in intact tissue was
      assessed by measuring the amount remaining in synaptosomal preparations after
      treatment of whole tecta with pharmacological agents. Use of this assay reveals
      that release of NT-3 from axon terminals is increased by depolarization, calcium
      influx via N-type calcium channels, and cAMP analogs, and release is most
      profoundly increased by excitation with kainic acid or mobilization of calcium
      from intracellular stores. NT-3 release depends on extracellular sodium, CaM
      kinase II activity, and requires intact microtubules and microfilaments.
      Dantrolene inhibits the high potassium-induced release of NT-3, indicating that
      release of calcium from intracellular stores is required. Tetanus toxin also
      inhibits NT-3 release, suggesting that intact synaptobrevin or synaptobrevin-like
      molecules are required for exocytosis. Ultrastructural autoradiography and
      immunolabel indicate that NT-3 is packaged in presumptive large dense-core
      vesicles. These data show that release of NT-3 from axon terminals depends on
      multiple regulatory proteins and ions, including the mobilization of local
      calcium. The data provide insight in the mechanisms of anterograde neurotrophins
      as synaptic modulators.

PMID- 11826124
TI  - Neurotransmitter regulation of cellular activation and neuropeptide gene
      expression in the paraventricular nucleus of the hypothalamus.
AB  - Norepinephrine (NE), glutamate (Glu), and GABA have been identified as important
      neurotransmitters governing neuroendocrine mechanisms represented in the
      paraventricular nucleus of the hypothalamus (PVH). Microinjection studies were
      used to compare the efficacy of these transmitter mechanisms in stimulating PVH
      output neurons. Local administration of NE provoked an increase in plasma
      corticosterone levels and Fos induction in the both the parvocellular and
      magnocellular divisions of the nucleus. This treatment also stimulated a robust
      increase in corticotropin-releasing factor (CRF) heteronuclear (hn) RNA in the
      parvocellular PVH and a more subtle, although reliable, increase in arginine
      vasopressin (AVP) hnRNA in this same compartment. Local administration of the
      GABA(A) receptor antagonist bicuculline methiodide (BMI) resulted in increased
      plasma corticosterone and, in contrast to NE treatment, Fos induction limited
      primarily to the parvocellular PVH. BMI elicited marked increases in both CRH and
      AVP hnRNAs within the parvocellular division of the nucleus. Over a wide range of
      concentrations, Glu failed to produce reliable increases in corticosterone
      secretion and induced only weak activational responses limited primarily to non
      neurosecretory regions of the PVH. Local Glu administration did, however, provoke
      Fos induction in identified GABAergic neurons immediately adjoining the PVH,
      suggesting that the muted response to Glu may be a consequence of concurrent
      activation of local inhibitory interneurons. These results support a differential
      involvement of adrenergic, glutamatergic and GABAergic mechanisms in regulating
      neurosecretory populations of the PVH and suggest that involvement of local
      circuit neurons must be carefully considered in the interpretation of
      microinjection studies.

PMID- 11826125
TI  - Dissociable neural responses related to pain intensity, stimulus intensity, and
      stimulus awareness within the anterior cingulate cortex: a parametric single
      trial laser functional magnetic resonance imaging study.
AB  - Neuroimaging studies have demonstrated activations in the anterior cingulate
      cortex (ACC) related to the affective component of pain, but not to stimulus
      intensity. However, it is possible that the low spatial resolution of positron
      emission tomography, as used in the majority of these studies, obscured areas
      coding stimulus intensity. We revisited this issue, using a parametric single
      trial functional magnetic resonance imaging design, and investigated pain,
      stimulus intensity, and stimulus awareness (i.e., pain unrelated) responses
      within the ACC in nine healthy volunteers. Four different stimulus intensities
      ranging from warm to painful (300-600 mJ) were applied with a thulium yttrium
      aluminum granite infrared laser in a randomized order and rated by the subjects
      on a five point scale (P0-P4). Pain-related regions in the ventral posterior ACC
      showed a response that did not distinguish between innocuous trials (P0 and P1)
      but showed a positive linear relationship with the blood oxygenation level
      dependent contrast signal for painful trials (P2-P4). Regions in the dorsal
      anterior ACC along the cingulate sulcus differentiated between P0 (not perceived)
      and P1 but exhibited no additional signal increase with P2; these regions are
      related to stimulus awareness and probably to cognitive processing. Most
      importantly, we identified a region in the dorsal posterior ACC showing a
      response that discriminated between nonpainful trials (P0 and P1); therefore,
      this region was simply related to basic sensory processing and not to pain
      intensity. Stimulus-related activations were all located adjacent to the
      cingulate motor area, highlighting the strategic link of stimulus processing and
      response generation in the posterior ACC.

PMID- 11826126
TI  - Afferents to the ventrolateral preoptic nucleus.
AB  - Sleep is influenced by diverse factors such as circadian time, affective states,
      ambient temperature, pain, etc., but pathways mediating these influences are
      unknown. To identify pathways that may influence sleep, we examined afferents to
      the ventrolateral preoptic nucleus (VLPO), an area critically implicated in
      promoting sleep. Injections of the retrograde tracer cholera toxin B subunit
      (CTB) into the VLPO produced modest numbers of CTB-labeled monoaminergic neurons
      in the tuberomammillary nucleus, raphe nuclei, and ventrolateral medulla, as well
      as a few neurons in the locus coeruleus. Immunohistochemistry for monoaminergic
      markers showed dense innervation of the VLPO by histaminergic, noradrenergic, and
      serotonergic fibers. Along with previous findings, these results suggest that the
      VLPO and monoaminergic nuclei may be reciprocally connected. Retrograde and
      anterograde tracing showed moderate or heavy inputs to the VLPO from hypothalamic
      regions including the median preoptic nucleus, lateral hypothalamic area, and
      dorsomedial hypothalamic nucleus (DMH), autonomic regions including the
      infralimbic cortex and parabrachial nucleus, and limbic regions including the
      lateral septal nucleus and ventral subiculum. Light to moderate inputs arose from
      orexin and melanin concentrating hormone neurons, but cholinergic or dopaminergic
      inputs were extremely sparse. Suprachiasmatic nucleus (SCN) projections to the
      VLPO were sparse, but the heavy input to the VLPO from the DMH, which receives
      direct and indirect SCN inputs, could provide an alternate pathway regulating the
      circadian timing of sleep. These robust pathways suggest candidate mechanisms by
      which sleep may be influenced by brain systems regulating arousal, autonomic,
      limbic, and circadian functions.

PMID- 11826127
TI  - Urocortin III-immunoreactive projections in rat brain: partial overlap with sites
      of type 2 corticotrophin-releasing factor receptor expression.
AB  - Urocortin (Ucn) III, or stresscopin, is a new member of the corticotropin
      releasing factor (CRF) peptide family identified in mouse and human.
      Pharmacological studies showed that Ucn III is a high-affinity ligand for the
      type 2 CRF receptor (CRF-R2). To further understand physiological functions the
      peptide may serve in the brain, the distribution of Ucn III neurons and fibers
      was examined by in situ hybridization and immunohistochemistry in the rat brain.
      Ucn III-positive neurons were found predominately within the hypothalamus and
      medial amygdala. In the hypothalamus, Ucn III neurons were observed in the median
      preoptic nucleus and in the rostral perifornical area lateral to the
      paraventricular nucleus. The Ucn III fibers were distributed mainly in the
      hypothalamus and limbic structures. Hypothalamic regions that were innervated
      prominently by Ucn III fibers included the ventromedial nucleus, medial preoptic
      nucleus, and ventral premammillary nucleus. Outside the hypothalamus, the densest
      projections were found in the intermediate part of the lateral septum, posterior
      division of the bed nucleus stria terminalis, and the medial nucleus of the
      amygdala. Several major Ucn III terminal fields identified in the present study,
      including the lateral septum and the ventromedial hypothalamus, are known to
      express high levels of CRF-R2. Thus, these anatomical data strongly support the
      notion that Ucn III is an endogenous ligand for CRF-R2 in these areas. These
      results also suggest that Ucn III is positioned to play a role in mediating
      physiological functions, including food intake and neuroendocrine regulation.

PMID- 11826128
TI  - Electrical synapses in the thalamic reticular nucleus.
AB  - Neurons of the thalamic reticular nucleus (TRN) provide inhibitory input to
      thalamic relay cells and generate synchronized activity during sleep and
      seizures. It is widely assumed that TRN cells interact only via chemical synaptic
      connections. However, we show that many neighboring pairs of TRN neurons in rats
      and mice are electrically coupled. In paired-cell recordings, electrical synapses
      were able to mediate close correlations between action potentials when the
      coupling was strong; they could modulate burst-firing states even when the
      coupling strength was more modest. Electrical synapses between TRN neurons were
      absent in mice with a null mutation for the connexin36 (Cx36) gene. Surprisingly,
      inhibitory chemical synaptic connections between pairs of neurons were not
      observed, although strong extracellular stimuli could evoke inhibition in single
      TRN neurons. We conclude that Cx36-dependent gap junctions play an important role
      in the regulation of neural firing patterns within the TRN. When combined with
      recent observations from the cerebral cortex, our results imply that electrical
      synapses are a common mechanism for generating synchrony within networks of
      inhibitory neurons in the mammalian forebrain.

PMID- 11826129
TI  - The 5-HT3 subtype of serotonin receptor contributes to nociceptive processing via
      a novel subset of myelinated and unmyelinated nociceptors.
AB  - Serotonin is a major component of the inflammatory chemical milieu and
      contributes to the pain of tissue injury via an action on multiple receptor
      subtypes. Here we studied mice after genetic or pharmacological disruption of the
      5-HT(3) receptor, an excitatory serotonin-gated ion channel. We demonstrate that
      tissue injury-induced persistent, but not acute, nociception is significantly
      reduced after functional elimination of this receptor subtype. Specifically, in
      the setting of tissue injury, the 5-HT(3) receptor mediates activation of
      nociceptors but does not contribute to injury-associated edema. This result is
      explained by the localization of 5-HT(3) receptor transcripts to a previously
      uncharacterized subset of myelinated and unmyelinated afferents, few of which
      express the proinflammatory neuropeptide substance P. Finally, we provide
      evidence that central serotonergic circuits modulate nociceptive transmission via
      a facilitatory action at spinal 5-HT(3) receptors. We conclude that activation of
      both peripheral and central 5-HT(3) receptors is pronociceptive and that the
      contribution of peripheral 5-HT(3) receptors involves a novel complement of
      primary afferent nociceptors.

PMID- 11826130
TI  - The role of corticotropin-releasing hormone in the dorsal raphe nucleus in
      mediating the behavioral consequences of uncontrollable stress.
AB  - Inescapable shock (IS) produces subsequent interference with escape behavior and
      increased fear conditioning that has been linked to increased activity and
      release of serotonin (5-HT) from neurons within the caudal dorsal raphe nucleus
      (DRN) both at the time of IS and later behavioral testing. Extrahypothalamic
      corticotropin-releasing hormone (CRH) has been implicated in many stress-related
      phenomena and has recently been shown to increase DRN 5-HT activity in the same
      caudal DRN area at which IS increases 5-HT activity. The current set of studies
      therefore examined the role of CRH in mediating the behavioral sequelae of IS.
      Intra-DRN microinjection of the nonselective CRH receptor antagonist d-Phe CRH
      (12-41) blocked the IS-induced behavioral changes when administered before IS but
      not when administered before later behavioral testing. Furthermore, intra-DRN
      administration of CRH in the absence of IS dose-dependently mimicked the effects
      of IS and interfered with escape behavior and increased fear conditioning 24 hr
      later. This effect was specific to injection of CRH into the caudal DRN and was
      not produced by microinjection into the rostral DRN. Intracerebroventricular CRH
      produced escape deficits and potentiated fear conditioning 24 hr later at only
      much higher doses, further confirming the site specificity of the effects. The
      potential role of the caudal DRN in states of anxiety is discussed.

PMID- 11826131
TI  - Sexual differentiation of the bed nucleus of the stria terminalis in humans may
      extend into adulthood.
AB  - Gonadal steroids have remarkable developmental effects on sex-dependent brain
      organization and behavior in animals. Presumably, fetal or neonatal gonadal
      steroids are also responsible for sexual differentiation of the human brain. A
      limbic structure of special interest in this regard is the sexually dimorphic
      central subdivision of the bed nucleus of the stria terminalis (BSTc), because
      its size has been related to the gender identity disorder transsexuality. To
      determine at what age the BSTc becomes sexually dimorphic, the BSTc volume in
      males and females was studied from midgestation into adulthood. Using vasoactive
      intestinal polypeptide and somatostatin immunocytochemical staining as markers,
      we found that the BSTc was larger and contains more neurons in men than in women.
      However, this difference became significant only in adulthood, showing that
      sexual differentiation of the human brain may extend into the adulthood. The
      unexpectedly late sexual differentiation of the BSTc is discussed in relation to
      sex differences in developmental, adolescent, and adult gonadal steroid levels.

PMID- 11826132
TI  - Chronic morphine treatment modulates the extracellular levels of endogenous
      enkephalins in rat brain structures involved in opiate dependence: a
      microdialysis study.
AB  - The endogenous opioid system is often assumed to play a role in vulnerability to
      drug abuse. However, controversial results have been reported regarding the
      levels of enkephalins or preproenkephalin in neurons of rodent brains after
      opiate administration. The present study was performed to determine the
      extracellular levels of enkephalins and its physiological antagonist
      cholecystokinin (CCK), using in vivo microdialysis in freely moving rats after
      morphine-induced physical dependence or positive place conditioning. A large
      increase (340%) of Met-enkephalin was observed in the periaqueductal gray matter,
      a structure involved in morphine withdrawal syndrome, in morphine-dependent rats.
      No change in CCK immunoreactivity occurred in these conditions. Moreover, using
      the conditioning place preference paradigm, we observed for the first time
      opposite changes of enkephalin outflow in the nucleus accumbens (NAc). Thus, an
      increase in enkephalin levels was observed in rats placed in the drug-associated
      compartment and a decrease in the saline-paired side. These changes in opioid
      peptides in the NAc may reflect an "emotional state" of the animals in relation
      to the expectation of drug reward (reinforcing effects of morphine). Moreover,
      the lack of regulation in CCK outflow suggests that CCK-opioid interactions in
      morphine dependence involve probably post-receptor events.

PMID- 11826133
TI  - Spatial buffering during slow and paroxysmal sleep oscillations in cortical
      networks of glial cells in vivo.
AB  - The ability of neuroglia to buffer local increases of extracellular K(+) has been
      known from in vitro studies. This property may confer on these cells an active
      role in the modulation and spreading of cortical oscillatory activities. We
      addressed the question of the spatial buffering in vivo by performing single and
      double intraglial recordings, together with measures of the extracellular K(+)
      and Ca(2+) concentrations ([K(+)](out) and [Ca(2+)](out)) in the cerebral cortex
      of cats under ketamine and xylazine anesthesia during patterns of slow sleep
      oscillations and spike-wave seizures. In addition, we estimated the fluctuations
      of intraglial K(+) concentrations ([K(+)](in)). Measurements obtained during the
      slow oscillation indicated that glial cells phasically take up part of the
      extracellular K(+) extruded by neurons during the depolarizing phase of the slow
      oscillation. During this condition, the redistribution of K(+) appeared to be
      local. Large steady increases of [K(+)](out) and phasic potassium accumulations
      were measured during spike-wave seizures. In this condition, [K(+)](in) rose
      before [K(+)](out) if the glial cells were located at some distance from the
      epileptic focus, suggesting faster K(+) diffusion through the interglial
      syncytium. The simultaneously recorded [Ca(2+)](out) dropped steadily during the
      seizures to levels incompatible with efficient synaptic transmission, but also
      displayed periodic oscillations, in phase with the intraseizure spike-wave
      complexes. In view of this fact, and considering the capability of K(+) to
      modulate neuronal excitability both at the presynaptic and postsynaptic levels,
      we suggest that the K(+) long-range spatial buffering operated by glia is a
      parallel synchronizing and/or spreading mechanism during paroxysmal oscillations.

PMID- 11826134
TI  - Persistent behavioral sensitization to chronic L-DOPA requires A2A adenosine
      receptors.
AB  - To investigate the role of A(2A) adenosine receptors in adaptive responses to
      chronic intermittent dopamine receptor stimulation, we compared the behavioral
      sensitization elicited by repeated l-DOPA treatment in hemiparkinsonian wild-type
      (WT) and A(2A) adenosine receptor knock-out (A(2A) KO) mice. Although the
      unilateral nigrostriatal lesion produced by intrastriatal injection of 6
      hydroxydopamine was indistinguishable between WT and A(2A) KO mice, they
      developed strikingly different patterns of behavioral sensitization after daily
      treatment with low doses of l-DOPA for 3 weeks. WT mice initially displayed
      modest contralateral rotational responses and then developed progressively
      greater responses that reached a maximum within 1 week and persisted for the
      duration of the treatment. In contrast, any rotational behavioral sensitization
      in A(2A) KO mice was transient and completely reversed within 2 weeks. Similarly,
      the time to reach the peak rotation was progressively shortened in WT mice but
      remained unchanged in A(2A) KO mice. Furthermore, daily l-DOPA treatment produced
      gradually sensitized grooming in WT mice but failed to induce any sensitized
      grooming in A(2A) KO mice. Finally, repeated l-DOPA treatment reversed the 6-OHDA
      induced reduction of striatal dynorphin mRNA in WT but not A(2A) KO mice, raising
      the possibility that the A(2A) receptor may contribute to l-DOPA-induced
      behavioral sensitization by facilitating adaptations within the dynorphin
      expressing striatonigral pathway. Together these results demonstrate that the
      A(2A) receptor plays a critical role in the development and particularly the
      persistence of behavioral sensitization to repeated l-DOPA treatment.
      Furthermore, they raise the possibility that the maladaptive dyskinetic responses
      to chronic l-DOPA treatment in Parkinson's disease may be attenuated by A(2A)
      receptor inactivation.

PMID- 11826135
TI  - Appetitive instrumental learning requires coincident activation of NMDA and
      dopamine D1 receptors within the medial prefrontal cortex.
AB  - Through its complex role in cognition, memory, and emotion, the mammalian
      prefrontal cortex is thought to contribute to the organization of adaptive
      behavioral actions. In the present studies we examined the role of dopaminergic
      D1 and glutamatergic NMDA receptors within the prefrontal cortex of the rat
      during the development of adaptive instrumental learning. Hungry rats with
      bilateral indwelling cannulas aimed at the medial prefrontal cortex were trained
      to lever-press for food. Infusion of the selective D1 antagonist SCH-23390 (0.15,
      0.3, 3.0 nmol) dose-dependently impaired acquisition of this behavior. Higher
      doses also impaired expression of this task. Co-infusion of the lowest dose of
      SCH 23390 with a low dose of the NMDA antagonist AP-5 (0.5 nmol), each of which
      had no effect on learning when infused alone, potently reduced the ability to
      acquire the response. Inhibition of intracellular protein kinase A with the
      selective PKA inhibitor Rp-cAMPS also disrupted acquisition, suggesting that PKA
      is an intracellular substrate for a D1-NMDA receptor interaction. In control
      experiments, drug infusions that impaired learning did not affect food intake or
      locomotion, suggesting a specific effect on learning. We hypothesize that
      coincident detection of D1-NMDA receptor activation and its transcriptional
      consequences, within multiple sites of a distributed corticostriatal network, may
      represent a conserved molecular mechanism for instrumental learning.

PMID- 11826136
TI  - Brain and body hyperthermia associated with heroin self-administration in rats.
AB  - Intravenous heroin self-administration in trained rats was accompanied by robust
      brain hyperthermia (+2.0-2.5 degrees C); parallel changes were found in the
      dorsal and ventral striatum, mediodorsal thalamus, and deep temporal muscle.
      Temperature began to increase at variable latency after a signal of drug
      availability, increased reliably (approximately 0.4 degrees C) before the first
      lever press for heroin, increased further (approximately 1.2 degrees C) after the
      first heroin injection, and rose more slowly after the second and third
      injections to stabilize at an elevated plateau (39-40 degrees C) for the
      remainder of the session. Brain and body temperature declined slowly when drug
      self-administration was terminated; naloxone precipitated a much more rapid
      decrease to baseline levels. Changes in temperature were similar across repeated
      daily sessions, except for the increase associated with the first self
      administration of each session, which had progressively shorter latency and
      greater acceleration. Despite consistent biphasic fluctuations in movement
      activity associated with heroin self-administrations (gradual increase preceding
      the lever press, followed by an abrupt hypodynamia after drug infusion), mean
      brain temperature was very stable at an elevated plateau. Only mean muscle
      temperature showed evidence of biphasic fluctuations (+/-0.2 degrees C) that were
      time locked to and correlated with lever pressing and associated movements. Drug-
      and behavior-related changes in brain temperature thus appear to reflect some
      form of neuronal activation, and, because temperature is a factor capable of
      affecting numerous neural functions, it may be an important variable in the
      control of behavior by drugs of abuse.

PMID- 11826137
TI  - Simulations of the role of the muscarinic-activated calcium-sensitive nonspecific
      cation current INCM in entorhinal neuronal activity during delayed matching
      tasks.
AB  - Entorhinal lesions impair performance in delayed matching tasks, and blockade of
      muscarinic cholinergic receptors also impairs performance in these tasks.
      Physiological data demonstrate that muscarinic cholinergic receptor stimulation
      activates intrinsic cellular currents in entorhinal neurons that could underlie
      the role of entorhinal cortex in performance of these tasks. Here we use a
      network biophysical simulation of the entorhinal cortex to demonstrate the
      potential role of this cellular mechanism in the behavioral tasks. Simulations
      demonstrate how the muscarinic-activated calcium-sensitive nonspecific cation
      current I(NCM) could provide a cellular mechanism for features of the neuronal
      activity observed during performance of delayed matching tasks. In particular,
      I(NCM) could underlie (1) the maintenance of sustained spiking activity during
      the delay period, (2) the enhancement of spiking activity during the matching
      period relative to the sample period, and (3) the resistance of sustained
      activity to distractors. Simulation of a larger entorhinal network with
      connectivity chosen randomly within constraints on number, distribution, and
      weight demonstrates appearance of other phenomena observed in unit recordings
      from awake animals, including match suppression, non-match enhancement, and non
      match suppression.

PMID- 11826138
TI  - Effects of activation of the histaminergic tuberomammillary nucleus on visual
      responses of neurons in the dorsal lateral geniculate nucleus.
AB  - We investigated the effects of the central histaminergic system on afferent
      sensory signals in the retinogeniculocortical pathway in the intact brain.
      Extracellular physiological recordings in vivo were obtained from neurons in the
      cat dorsal lateral geniculate nucleus (LGN) in conjunction with electrical
      activation of the histamine-containing cells in the tuberomammillary nucleus of
      the hypothalamus. Tuberomammillary activation resulted in a rapid and significant
      increase in the amplitude of baseline activity and visual responses in LGN
      neurons. Geniculate X- and Y-cells were affected similarly. LGN cells that
      exhibited a burst pattern of activity in the control condition switched to a
      tonic firing pattern during tuberomammillary activation. Effects on visual
      response properties were assessed using drifting sinusoidal gratings of varied
      spatial frequency. The resultant spatial tuning curves were elevated by
      tuberomammillary activation, but there was no change in tuning curve shape.
      Rather, the effect was proportionate to the control response, with the greatest
      tuberomammillary effects at spatial frequencies already optimal for the cell.
      Tuberomammillary activation caused a small phase lag in the visual response that
      was similar at all spatial frequencies, consistent with the induced shift from
      burst to tonic firing mode. These results indicate a significant histaminergic
      effect on LGN thalamocortical cells, with no clear effect on thalamic inhibitory
      neurons. The histaminergic system appears to strengthen central transmission of
      afferent information, intensifying but not transforming the retinally derived
      signals. Promoting sensory input may be one way in which the histaminergic system
      plays a role in arousal.

PMID- 11826139
TI  - Kinematics and dynamics are not represented independently in motor working
      memory: evidence from an interference study.
AB  - Our capacity to learn multiple dynamic and visuomotor tasks is limited by the
      time between the presentations of the tasks. When subjects are required to adapt
      to equal and opposite position-dependent visuomotor rotations (Krakauer et al.,
      1999) or velocity-dependent force fields (Brashers-Krug et al., 1996) in quick
      succession, interference occurs that prevents the first task from being
      consolidated in memory. In contrast, such interference is not observed between
      learning a position-dependent visuomotor rotation and an acceleration-dependent
      force field. On the basis of this finding, it has been argued that internal
      models of kinematic and dynamic sensorimotor transformations are learned
      independently (Krakauer et al., 1999). However, these findings are also
      consistent with the perturbations interfering only if they depend on the same
      kinematic variable. We evaluated this hypothesis using kinematic and dynamic
      transformations matched in terms of the kinematic variable on which they depend.
      Subjects adapted to a position-dependent visuomotor rotation followed 5 min later
      by a position-dependent rotary force field either with or without visual feedback
      of arm position. The force field tended to rotate the hand in the direction
      opposite to the visuomotor rotation. To assess learning, all subjects were
      retested 24 hr later on the visuomotor rotation, and their performance was
      compared with a control group exposed only to the visuomotor rotation on both
      days. Adapting to the position-dependent force field, both with and without
      visual feedback, impaired learning of the visuomotor rotation. Thus, interference
      between our kinematic and dynamic transformations was observed, suggesting that
      the key determinant of interference is the kinematic variable on which the
      transformation depends.

PMID- 11826140
TI  - Neurons of the central complex of the locust Schistocerca gregaria are sensitive
      to polarized light.
AB  - The central complex is a topographically ordered neuropil structure in the center
      of the insect brain. It consists of three major subdivisions, the upper and lower
      divisions of the central body and the protocerebral bridge. To further
      characterize the role of this brain structure, we have recorded the responses of
      identified neurons of the central complex of the desert locust Schistocerca
      gregaria to visual stimuli. We report that particular types of central complex
      interneurons are sensitive to polarized light. Neurons showed tonic responses to
      linearly polarized light with spike discharge frequencies depending on e-vector
      orientation. For all neurons tested, e-vector response curves showed polarization
      opponency. Receptive fields of the recorded neurons were in the dorsal field of
      view with some neurons receiving input from both compound eyes and others, only
      from the ipsilateral eye. In addition to responses to polarized light, certain
      neurons showed tonic spike discharges to unpolarized light. Most polarization
      sensitive neurons were associated with the lower division of the central body,
      but one type of neuron with arborizations in the upper division of the central
      body was also polarization-sensitive. Visual pathways signaling polarized light
      information to the central complex include projections via the anterior optic
      tubercle. Considering the receptive fields of the neurons and the biological
      significance of polarized light in insects, the central complex might serve a
      function in sky compass-mediated spatial navigation of the animals.

PMID- 11826141
TI  - Dissociable effects of lidocaine inactivation of the rostral and caudal
      basolateral amygdala on the maintenance and reinstatement of cocaine-seeking
      behavior in rats.
AB  - Cocaine addiction is a chronically relapsing brain disease, but its neural basis
      is not yet well understood. Clinical reports underscore the possible importance
      of associative processes for regulating at least some aspects of cocaine
      addiction. The present study reports the effects of reversible lidocaine-induced
      inactivation of rostral basolateral amygdala (rBLA) and caudal basolateral
      amygdala (cBLA) regions on the maintenance and reinstatement of drug-seeking
      behavior in rats trained to self-administer 1 mg/kg cocaine under a second order
      schedule of drug delivery. Both regions of the basolateral amygdala were
      investigated because they have dissociable effects on cognitive task performance.
      Results demonstrated that after self-administration training and a period of
      extinction and abstinence, lidocaine inactivation of the rBLA and cBLA attenuated
      the reinstatement of drug-seeking behavior induced by cocaine-associated cues
      examined in conjunction with a single priming injection of cocaine. In contrast,
      lidocaine inactivation of only the rBLA blocked reinstatement of drug-seeking
      behavior induced by cocaine-associated cues examined alone. Additional
      differences were shown during cocaine maintenance testing where inactivation of
      only the cBLA attenuated drug-seeking behavior. Drug intake was not altered.
      Thus, the rBLA and cBLA appear to selectively and dissociably regulate drug
      seeking behavior under conditions of cocaine abstinence (cue-induced
      reinstatement) and repeated cocaine use (maintenance), respectively. These
      findings suggest that the basolateral amygdala may be more functionally
      heterogeneous than commonly thought for regulating drug-seeking behavior. The
      basis for this dissociation might be related to neuroanatomical connections of
      the rBLA and cBLA with segregated, but parallel, corticostriatalpallidothalamic
      circuits.

PMID- 11826142
TI  - Glutamate receptor-dependent modulation of dopamine efflux in the nucleus
      accumbens by basolateral, but not central, nucleus of the amygdala in rats.
AB  - Dopaminergic neurotransmission in the nucleus accumbens (NAc) and neural
      processes in the basolateral (BLA) and central (CeN) amygdala nuclei are
      implicated in associative reward learning. Given their direct and indirect
      connections with the NAc and ventral tegmental area (VTA), both the BLA and CeN
      may regulate the mesoaccumbens dopamine (DA) system in rewarding situations.
      Electrical stimulation of the BLA (20 Hz, 10 sec, 300 microA) induced a long
      lasting 25 +/- 4% increase in DA efflux in the NAc, measured by microdialysis in
      freely moving rats, whereas comparable stimulation of the CeN had no effect.
      Reverse dialysis of either the NMDA receptor antagonist APV (100 micrometer) or
      the AMPA-kainate receptor antagonist DNQX (100 micrometer), but not the
      metabotropic glutamate receptor antagonist (+/-)-amino-4-carboxy-methyl
      phenylacetic acid (100 micrometer), into the NAc blocked the stimulation-evoked
      increase in DA efflux in the NAc. VTA infusion of lidocaine (lido; 4%)
      significantly reduced basal DA levels for approximately 30 min but failed to
      suppress the increase in NAc DA efflux resulting from BLA stimulation.
      Additionally, infusions of lido (4%) into the medial prefrontal cortex failed to
      block the stimulation-evoked increase in NAc DA efflux. These data support the
      hypothesis that the BLA can directly modulate DA efflux through local mechanisms
      in the NAc, independent of an action on DA cell bodies in the VTA. The finding
      that brief activation of the CeN had no long-lasting effects on DA efflux in the
      NAc suggests an important degree of functional independence between the CeN and
      BLA.

PMID- 11826143
TI  - Motivational effects of cannabinoids are mediated by mu-opioid and kappa-opioid
      receptors.
AB  - Repeated THC administration produces motivational and somatic adaptive changes
      leading to dependence in rodents. To investigate the molecular basis for
      cannabinoid dependence and its possible relationship with the endogenous opioid
      system, we explored delta9-tetrahydrocannabinol (THC) activity in mice lacking mu
      , delta- or kappa-opioid receptor genes. Acute THC-induced hypothermia,
      antinociception, and hypolocomotion remained unaffected in these mice, whereas
      THC tolerance and withdrawal were minimally modified in mutant animals. In
      contrast, profound phenotypic changes are observed in several place conditioning
      protocols that reveal both THC rewarding and aversive properties. Absence of
      microreceptors abolishes THC place preference. Deletion of kappa receptors
      ablates THC place aversion and furthermore unmasks THC place preference. Thus, an
      opposing activity of mu- and kappa-opioid receptors in modulating reward pathways
      forms the basis for the dual euphoric-dysphoric activity of THC.

PMID- 11826144
TI  - Impaired spatial performance in rats with retrosplenial lesions: importance of
      the spatial problem and the rat strain in identifying lesion effects in a
      swimming pool.
AB  - Behavioral, electrophysiological, and anatomical evidence suggests that
      retrosplenial (RS) cortex (areas RSA and RSG) plays a role in spatial navigation.
      This conclusion has been questioned in recent work, suggesting that it is damage
      to the underlying cingulum bundle (CG) (areas CG and IG), and not RS, that
      disrupts spatial place learning (Aggleton et al., 2000). We revisited this issue
      by comparing Long-Evans rats, the strain used in studies that report RS deficits,
      to Dark Agouti rats, the strain in which no RS deficit has been reported. Rat
      groups with RS, RS + CG, or no lesion were tested on a place task in a swimming
      pool, a test of nonspatial and spatial learning, and a matching-to-place task, a
      relatively selective test of spatial learning. Long-Evans rats given RS and RS +
      CG lesions, either before or after training on the two tasks, were impaired on
      both tasks, a deficit not attributable to impaired visual acuity. Control Dark
      Agouti rats and RS Dark Agouti rats, although not different on the place task,
      were both significantly impaired relative to Long-Evans rats. The RS Dark Agouti
      group, however, was also impaired on the matching-to-place task. Thus, we show
      that RS cortex is part of an extended neural circuit involved in spatial behavior
      in both Long-Evans and Dark Agouti rats, but its role in the place task may be
      masked by an innate nonspatial deficit in Dark Agouti rats. The results are
      discussed in relation to the importance of assessing spatial learning with
      appropriate spatial tests, the problems of interpretation posed by rat strain
      differences, and the role of retrosplenial cortex in spatial behavior.

PMID- 11826145
TI  - Identification of quantitative trait Loci that affect aggressive behavior in
      mice.
AB  - Despite the previous development of single-gene knock-out mice that exhibit
      alterations in aggressive behavior, very little progress has been made toward
      identifying the natural gene variants (alleles) that contribute to individual or
      strain differences in aggression. Whereas most inbred mouse strains show an
      intermediate level of inter-male aggression in the resident-intruder or dangler
      behavioral tests, NZB/B1NJ mice are extremely aggressive and A/J mice are
      extremely unaggressive. We took advantage of the large phenotypic difference
      between these strains and used an outcross-backcross breeding protocol and a
      genome-wide scan to identify aggression quantitative trait loci (QTLs) on distal
      chromosome 10 (Aggr1; p = 6 x 10(-7)) and proximal chromosome X (Aggr2; p = 2.14
      x 10(-5)). Candidate genes for Aggr1 and Aggr2, respectively, include the
      diacylglycerol kinase alpha subunit gene (Dagk1) and the glutamate receptor
      subunit AMPA3 gene (Gria3). This is the first report of significant aggression
      QTLs established through a genome-wide scan in any mammal. The mapping of these
      QTLs is a step toward the definitive identification of mouse alleles that affect
      aggression and may lead, ultimately, to the discovery of homologous alleles that
      affect individual differences in aggression within other mammalian species.

PMID- 11826146
TI  - Competition between memory systems: acetylcholine release in the hippocampus
      correlates negatively with good performance on an amygdala-dependent task.
AB  - Lesions of the amygdala impair acquisition of a food conditioned place preference
      (CPP) task. In contrast, lesions of the fornix facilitate acquisition on this
      task, showing that an intact hippocampal system can interfere with learning an
      amygdala-dependent task. Our recent findings indicate that acetylcholine (ACh)
      release in the hippocampus increases while rats perform a hippocampus-dependent
      spontaneous alternation task. To the extent that ACh output in the hippocampus
      reflects activation of that brain area in learning and memory, the results
      obtained with fornix lesions suggest that ACh release in the hippocampus might be
      negatively correlated with learning on a CPP task. Using in vivo microdialysis,
      release of ACh was measured in the hippocampus while rats learned and were tested
      on an amygdala-dependent CPP task and a hippocampus-dependent spontaneous
      alternation task. Release of ACh in the hippocampus increased when rats were
      tested on either task. The magnitude of the increase in release of hippocampal
      ACh was negatively correlated with good performance on the amygdala-dependent CPP
      task. These findings suggest that ACh release may reflect activation and
      participation of the hippocampus in learning and memory, but in a manner that can
      be detrimental to performance on a task dependent on another brain area.

PMID- 11826147
TI  - Short-term and long-term effects of vocal distortion on song maintenance in zebra
      finches.
AB  - Adult zebra finch song is irreversibly altered when birds are deprived of correct
      feedback by deafening or denervation of the syrinx. To clarify the role of
      feedback in song maintenance, we developed a reversible technique to distort
      vocal output without damaging the auditory or vocal systems. We implanted
      flexible beads adjacent to the syrinx to alter its biomechanics. Immediate song
      aberrations included low volume, frequency shifts, missing harmonics, and
      production of click-like syllables. After a few weeks, seven of nine birds
      stopped producing some syllables. In six of these birds, the gaps left by the
      silenced syllables gradually shortened, and the lost syllables did not return
      when beads were removed 16 weeks after treatment began. The nondeleted syllables
      of all birds regained their preimplant morphology, insofar as could be detected,
      within 9 d after bead removal. In four other birds, we removed the beads as soon
      as syllables were deleted, when the silent intervals were still full length. In
      these birds, all deleted syllables returned within 1 week. Our results indicate
      that both silenced syllables and syllable morphology can recover as long as the
      song's temporal structure is maintained, but once altered, changes in the song
      sequence can be permanent. A hierarchical organization of the song production
      system has recently been described (Margoliash, 1997). Reversible disruption of
      song production by our method appears to permanently alter the higher levels of
      the system that encode song sequence, but not the lower levels that encode
      individual syllable structure.

PMID- 11826148
TI  - Burst discharge in primary sensory neurons: triggered by subthreshold
      oscillations, maintained by depolarizing afterpotentials.
AB  - Afferent discharge generated ectopically in the cell soma of dorsal root ganglion
      (DRG) neurons may play a role in normal sensation, and it contributes to
      paraesthesias and pain after nerve trauma. This activity is critically dependent
      on subthreshold membrane potential oscillations; oscillatory sinusoids that reach
      threshold trigger low-frequency trains of intermittent spikes. Ectopic firing may
      also enter a high-frequency bursting mode, however, particularly in the event of
      neuropathy. Bursting greatly amplifies the overall ectopic barrage. In the
      present report we show that subthreshold oscillations and burst discharge occur
      in vivo, as they do in vitro. We then show that although the first spike in each
      burst is triggered by an oscillatory sinusoid, firing within bursts is maintained
      by brief regenerative post-spike depolarizing afterpotentials (DAPs). Numerical
      simulations were used to identify the cellular process underlying rebound DAPs,
      and hence the mechanism of the spike bursts. Finally, we show that slow ramp and
      hold (tonic) depolarizations of the sort that occur in DRG neurons during
      physiologically relevant events are capable of triggering sustained ectopic
      bursting, but only in cells with subthreshold oscillatory behavior. Oscillations
      and DAPs are an essential substrate of ectopic burst discharge. Therefore, any
      consideration of the ways in which cellular regulation of ion channel synthesis
      and trafficking implement normal sensation and, when disrupted, bring about
      neuropathic pain must take into account the effects of this regulation on
      oscillations and bursting.

PMID- 11826149
TI  - Spatiotemporal pattern of motoneuron activation in the rostral lumbar and the
      sacral segments during locomotor-like activity in the neonatal mouse spinal cord.
AB  - We used calcium imaging to visualize the spatiotemporal pattern of motoneuron
      activity during dorsal root-evoked locomotor-like bursting in the lumbosacral
      spinal cord of the neonatal mouse. Dorsal root stimuli elicited a tonic discharge
      in motoneurons on which alternating left-right rhythmic discharges were
      superimposed. Both the tonic and the rhythmic components could be recorded
      optically from populations of motoneurons labeled with calcium-green dextran.
      Optical and electrical recordings revealed that rhythmic signals from different
      parts of the lumbar (L1, L2) and sacral (S1-S3) segments rose, peaked, and
      decayed in a rostrocaudal sequence. This pattern gave rise to a rostrocaudal
      "wave" in the activation of motoneurons during each cycle of locomotor-like
      activity. A similar rostrocaudal delay was observed during episodes of
      alternation that occurred in the absence of stimulation, suggesting that this
      delay was not caused by the train of dorsal root stimuli. It is hypothesized that
      this behavior may simplify the appropriate sequencing of motoneurons during
      locomotion.

PMID- 11826150
TI  - Place-cell impairment in glutamate receptor 2 mutant mice.
AB  - There is a strong correlation between Hebbian, NMDA receptor-dependent long-term
      potentiation (LTP), place-cell firing, and learning and memory. We made glutamate
      receptor 2 (GluR2) null mutant mice that show enhanced non-Hebbian LTP in
      hippocampal CA1 neurons and impaired performance in a spatial learning task. We
      concluded that in vivo hippocampal place cells of GluR2 mutant mice were
      functionally impaired because (1) only 22.6% of CA1 neurons showed place fields
      in GluR2 mutant mice, which was significantly lower than that (43.8%) in wild
      type mice; (2) GluR2 mutant place fields were much less precise; and (3) GluR2
      mutant place fields were extremely unstable. Our data suggest that place cells of
      GluR2 knock-out mice did not form robust place fields, and that enhanced non
      Hebbian LTP might play a negative role in their formation.

PMID- 11826151
TI  - Neuromagnetic responses to frequency-tagged sounds: a new method to follow inputs
      from each ear to the human auditory cortex during binaural hearing.
AB  - Binaural cortical responses are mixtures of inputs from both ears. We introduce
      here a novel method that allows, for the first time, to selectively follow these
      inputs in humans up to the cortex during binaural hearing. We recorded
      neuromagnetic cortical responses to amplitude-modulated continuous tones, with
      different modulation frequencies at each ear. During binaural hearing, the left-
      and right-ear inputs competed strongly in both auditory cortices: the right
      hemisphere responses were symmetrically suppressed, compared with monaural
      stimulation, for sounds of both ears, whereas the left-hemisphere responses were
      suppressed significantly more for ipsilateral than contralateral sounds, thereby
      intensifying the right-ear dominance of the left auditory cortex. This type of
      hemisphere- and ear-selective information on cortical binaural interaction could
      have important applications in human auditory neuroscience.

PMID- 11826152
TI  - Aberrant expression of the glutamate transporter excitatory amino acid
      transporter 1 (EAAT1) in Alzheimer's disease.
AB  - Glutamate-mediated toxicity has been implicated in the neurodegeneration observed
      in Alzheimer's disease. In particular, glutamate transport dysfunction may
      increase susceptibility to glutamate toxicity, thereby contributing to neuronal
      cell injury and death. In this study, we examined the cellular localization of
      the glial glutamate transporter excitatory amino acid transporter 1 (EAAT1) in
      the cerebral cortex of control, Alzheimer's disease, and non-Alzheimer dementia
      cases. We found that EAAT1 was strongly expressed in a subset of cortical
      pyramidal neurons in dementia cases showing Alzheimer-type pathology. In
      addition, tau (which is a marker of neurofibrillary pathology) colocalized to
      those same pyramidal cells that expressed EAAT1. These findings suggest that
      EAAT1 changes are related to tau expression (and hence neurofibrillary tangle
      formation) in dementia cases showing Alzheimer-type pathology. This study
      implicates aberrant glutamate transporter expression as a mechanism involved in
      neurodegeneration in Alzheimer's disease.

PMID- 11826153
TI  - Role of the posterior parietal cortex in spatial hearing.
AB  - The human posterior parietal cortex (PPC) is well known to be involved in various
      functions of multisensory spatial perception. However, the specific role of the
      PPC in hearing has, up to now, remained unclear. To allow more reliable
      conclusions to be drawn on this issue, we have used repetitive transcranial
      magnetic stimulation in healthy subjects. Focal stimulation of the PPC induced a
      systematic shift in the lateralization of interaural time differences (ITDs, a
      main cue for auditory azimuth), whereas the acuity of ITD discrimination was
      unaffected. We propose that the PPC is specifically involved in relating
      azimuthal angles of sound to the body coordinates and is part of a "where" stream
      in cortical processing of auditory information.

PMID- 11826154
TI  - Voluntary alcohol consumption is controlled via the neuropeptide Y Y1 receptor.
AB  - We have shown previously that voluntary ethanol consumption and resistance to
      ethanol-induced sedation are inversely related to neuropeptide Y (NPY) levels in
      NPY-knock-out (NPY(-/-)) and NPY-overexpressing mice. In the present report, we
      studied knock-out mice completely lacking the NPY Y1 receptor (Y1(-/-)) to
      further characterize the role of the NPY system in ethanol consumption and
      neurobiological responses to this drug. Here we report that male Y1(-/-) mice
      showed increased consumption of solutions containing 3, 6, and 10% (v/v) ethanol
      when compared with wild-type (Y1(+/+)) control mice. Female Y1(-/-) mice showed
      increased consumption of a 10% ethanol solution. In contrast, Y1(-/-) mice showed
      normal consumption of solutions containing either sucrose or quinine. Relative to
      Y1(+/+) mice, male Y1(-/-) mice were found to be less sensitive to the sedative
      effects of 3.5 and 4.0 gm/kg ethanol as measured by more rapid recovery from
      ethanol-induced sleep, although plasma ethanol levels did not differ
      significantly between the genotypes. Finally, male Y1(-/-) mice showed normal
      ethanol-induced ataxia on the rotarod test after administration of a 2.5 gm/kg
      dose. These data suggest that the NPY Y1 receptor regulates voluntary ethanol
      consumption and some of the intoxicating effects caused by administration of
      ethanol.

PMID- 11826155
TI  - Unravelling the role of the ryanodine receptor type 3 in smooth muscle.

PMID- 11826156
TI  - Short chained fatty acids and the colon: how do they cause vasodilatation?

PMID- 11826157
TI  - Isoform-specific effects of sialic acid on voltage-dependent Na+ channel gating:
      functional sialic acids are localized to the S5-S6 loop of domain I.
AB  - The isoform specific role of sialic acid in human voltage-gated sodium channel
      gating was investigated through expression and chimeric analysis of two human
      isoforms, Na(v1.4) (hSkM1), and Na(v1.5) (hH1) in Chinese hamster ovary (CHO)
      cell lines. Immunoblot analyses indicate that both hSkM1 and hH1 are glycosylated
      and that hSkM1 is more glycosylated than hH1. Four sets of voltage-dependent
      parameters, the voltage of half-activation (V(a)), the voltage of half
      inactivation (V(i)), the time constants for fast inactivation (tau(h)), and the
      time constants for recovery from inactivation (tau(rec)), were measured for hSkM1
      and hH1 expressed in two CHO cell lines, Pro5 and Lec2, to determine the effect
      of changing sialylation on channel gating under conditions of full (Pro5) or
      reduced (Lec2) sialylation. For all parameters measured, hSkM1 gating showed a
      consistent 11-15 mV depolarizing shift under conditions of reduced sialylation,
      while hH1 showed no significant change in any gating parameter. Shifts in channel
      V(a) with changing external [Ca2+] indicated that sialylation of hSkM1, but not
      hH1, directly contributes to a negative surface potential. Functional analysis of
      two chimeras, hSkM1P1 and hH1P1, indicated that the responsible sialic acids are
      localized to the hSkM1 S5-S6 loop of domain I. When hSkM1 IS5-S6 was replaced by
      the analogous hH1 loop (hSkM1P1), changing sialylation had no significant effect
      on any voltage-dependent parameter. Conversely, when hSkM1 IS5-S6 was added to
      hH1 (hH1P1), all four parameters shifted by 6-7 mV in the depolarized direction
      under conditions of reduced sialylation. In summary, the gating of two human
      sodium channel isoforms show very different dependencies on sialic acid, with
      hSkM1 gating uniformly altered by sialic acid levels through an apparent
      electrostatic mechanism, while hH1 gating is unaffected by changing sialylation.
      Sialic acid-dependent gating can be removed or created by replacing or inserting
      hSkM1 IS5-S6, respectively, indicating that the functionally relevant sialic acid
      residues are localized to the first domain of the channel.

PMID- 11826158
TI  - Remodelling inactivation gating of Kv4 channels by KChIP1, a small-molecular
      weight calcium-binding protein.
AB  - Calcium-binding proteins dubbed KChIPs favour surface expression and modulate
      inactivation gating of neuronal and cardiac A-type Kv4 channels. To investigate
      their mechanism of action, Kv4.1 or Kv4.3 were expressed in Xenopus laevis
      oocytes, either alone or together with KChIP1, and the K+ currents were recorded
      using the whole-oocyte voltage-clamp and patch-clamp methods. KChIP1 similarly
      remodels gating of both channels. At positive voltages, KChIP1 slows the early
      phase of the development of macroscopic inactivation. By contrast, the late phase
      is accelerated, which allows complete inactivation in < 500 ms. Thus,
      superimposed traces from control and KChIP1-remodelled currents crossover. KChIP1
      also accelerates closed-state inactivation and recovery from inactivation (3- to
      5-fold change). The latter effect is dominating and, consequently, the prepulse
      inactivation curves exhibit depolarizing shifts (DeltaV = 4-12 mV). More
      favourable closed-state inactivation may also contribute to the overall faster
      inactivation at positive voltages because Kv4 channels significantly inactivate
      from the preopen closed state. KChIP1 favours this pathway further by
      accelerating channel closing. The peak G-V curves are modestly leftward shifted
      in the presence of KChIP1, but the apparent 'threshold' voltage of current
      activation remains unaltered. Single Kv4.1 channels exhibited multiple
      conductance levels that ranged between 1.8 and 5.6 pS in the absence of KChIP1
      and between 1.9 and 5.3 pS in its presence. Thus, changes in unitary conductance
      do not contribute to current upregulation by KChIP1. An allosteric kinetic model
      explains the kinetic changes by assuming that KChIP1 mainly impairs open-state
      inactivation, favours channel closing and lowers the energy barrier of closed
      state inactivation.

PMID- 11826159
TI  - Identification and function of ryanodine receptor subtype 3 in non-pregnant mouse
      myometrial cells.
AB  - Subtype 3 of the ryanodine receptor (RYR3) is a ubiquitous Ca2+ release channel
      which is predominantly expressed in smooth muscle tissues and certain regions of
      the brain. We show by reverse transcription-polymerase chain reaction (RT-PCR)
      that non-pregnant mouse myometrial cells expressed only RYR3 and therefore could
      be a good model for studying the role of endogenous RYR3. Expression of RYR3 was
      confirmed by Western blotting and immunostaining. Confocal Ca2+ measurements
      revealed that in 1.7 mM extracellular Ca2+, neither caffeine nor photolysis of
      caged Ca2+ were able to trigger any Ca2+ responses, whereas in the same cells
      oxytocin activated propagated Ca2+ waves. However, under conditions of increased
      sarcoplasmic reticulum (SR) Ca2+ loading, brought about by superfusing myometrial
      cells in 10 mM extracellular Ca2+, all the myometrial cells responded to caffeine
      and photolysis of caged Ca2+, indicating that it was possible to activate RYR3.
      The caffeine-induced Ca2+ responses were inhibited by intracellular application
      of an anti-RYR3-specific antibody. Immunodetection of RYR3 with the same antibody
      revealed a rather homogeneous distribution of fluorescence in confocal cell
      sections. In agreement with these observations, spontaneous or triggered Ca2+
      sparks were not detected. In conclusion, our results suggest that under
      conditions of increased SR Ca2+ loading, endogenous RYR3 may contribute to the
      Ca2+ responses of myometrial cells.

PMID- 11826160
TI  - A Ca2+-permeable non-selective cation channel activated by depletion of internal
      Ca2+ stores in single rabbit portal vein myocytes.
AB  - In vascular smooth muscle cells many agonists cause the release of Ca2+ ions from
      internal stores. An important problem concerns the mechanism by which the
      intracellular stores are refilled subsequent to depletion. In the present study,
      we describe the properties of a Ca2+-permeable non-selective cation channel
      current that is activated in rabbit portal vein myocytes by depletion of internal
      Ca2+ stores. Application of cyclopiazonic acid (CPA), which depletes internal
      Ca2+ stores, activated whole-cell currents that had a reversal potential (E(r))
      of about +50 mV in 1.5 mM external Ca2+ (Ca2+o). In 0 mM Ca2+o, the currents were
      larger and E(r) was approximately 0 mV. Application of CPA and caffeine during
      cell-attached recording activated single inward channel currents at negative
      potentials, which had a slope conductance of 2-3 pS and an E(r) of +20 mV. The
      slope conductance in 0 and 110 mM Ca2+o was 7 and 1.5 pS, respectively, and E(r)
      values indicated that these non-selective cation channels are highly permeable to
      Ca2+ ions. Bath application of the cell-permeant Ca2+ chelator, BAPTA-AM, also
      activated similar currents, indicating that these channels are not activated by
      Ca2+. Spontaneous channel currents with similar properties to store-operated
      channels were observed in some patches. Application of W-7, an inhibitor of the
      Ca2+-binding protein calmodulin, also activated similar Ca2+-permeable channel
      currents. In conclusion, it is demonstrated that agents that deplete Ca2+ stores
      and inhibit calmodulin binding activate Ca2+-permeable non-selective cation
      channel currents in rabbit portal vein myocytes. These channels may have an
      important role in vascular smooth muscle in providing an influx of Ca2+ to refill
      depleted internal Ca2+ stores and appear to possess different characteristics to
      store-operated channels described in other vascular smooth muscle preparations.

PMID- 11826161
TI  - Ca2+ transport properties and determinants of anomalous mole fraction effects of
      single voltage-gated Ca2+ channels in hair cells from bullfrog saccule.
AB  - We studied the permeation properties of two distinct single voltage-gated Ca2+
      channels in bullfrog saccular hair cells to assess the roles of the channels as
      physiological Ca2+ transporters and multi-ion pores. By varying the permeant ions
      (Ba2+, Ca2+) and concentrations (2-70 mM), we estimated the affinity constant
      (K(D)) of the two channels as follows (mM): L-type channel, K(D,Ba) = 7.4 +/-
      1.0, K(D,Ca) = 7.1 +/- 2.2 (n = 7); non-L-type channel, K(D,Ba) = 5.3 +/- 3.2,
      K(D,Ca) = 2.0 +/- 1.0 (n = 8). Using ionic concentrations close to physiological
      conditions (2 mM Ca2+ and 1.0 mM Mg2+), the conductance of the L-type channel was
      approximately 2 pS. We determined the mechanisms by which ions traverse the pore
      of these single Ca2+ channels, using mixtures of Ba2+ and Ca2+ at total
      concentrations above (70 mM) or close to (5 mM) the K(D) of the channels. We
      found evidence for an anomalous mole fraction effect (AMFE) only when the total
      divalent ion concentration was 5 mM, consistent with a multi-ion pore. We show
      that AMFE arises from the boundaries between the pore and bulk solution in the
      atria of the channel, which is derived from the presence of depletion zones that
      become apparent at low divalent cation concentrations. The present findings
      provide an explanation as to why previous whole-cell Ca2+ currents that were
      recorded in quasi-physiological Ca2+ concentrations (approximately 2-5 mM) showed
      clear AMFE, whereas single Ca2+ channel currents that were recorded routinely at
      high Ca2+ concentrations (20-110 mM) did not.

PMID- 11826163
TI  - Comparison of aconitine-modified human heart (hH1) and rat skeletal (mu1) muscle
      Na+ channels: an important role for external Na+ ions.
AB  - Neurotoxins such as aconitine (AC) bind to receptor site 2 on voltage-gated
      sodium channels and modify channel kinetics. Although AC modification typically
      induces hyperpolarizing shifts in sodium channel activation, the effects on
      channel inactivation seem to vary depending on the tissue origin of the channel.
      In the present study, the alpha subunits of human heart (hH1) and rat skeletal
      muscle (mu1) sodium channels were transiently expressed in human embryonic kidney
      (HEK293t) cells. Whole-cell currents were examined before and after AC
      modification of the channels to determine whether the toxin had isoform-specific
      effects on channel kinetics. The magnitudes of the hyperpolarizing shifts in
      steady-state current activation and inactivation were similar for AC-modified hH1
      and mu1 channels, and AC modification did not alter the voltage dependence of
      macroscopic current decay of either channel subtype. There were two notable
      differences between hH1 and mu1 channels after AC modification. First, the steady
      state availability of AC-modified mu1 channels decreased by 5-10% after very
      negative conditioning pulses. Second, AC-modified mu1 channels inactivated
      completely at all voltages, whereas AC-modified hH1 channels exhibited sustained
      inward currents at voltages near the threshold of current activation.
      Interestingly, AC-modified hH1 channels inactivated completely if the external
      solution did not contain sodium ions. The data demonstrate that AC modification
      affects the activation of hH1 and mu1 channels similarly but affects inactivation
      of the two channels distinctly. The results also imply that the reduced
      inactivation of AC-modified hH1 channels at least partially depends on the
      presence of extracellular sodium.

PMID- 11826162
TI  - Characterization of basolateral K+ channels underlying anion secretion in the
      human airway cell line Calu-3.
AB  - Transepithelial anion secretion in many tissues depends upon the activity of
      basolateral channels. Using monolayers of the Calu-3 cell line, a human
      submucosal serous cell model mounted in an Ussing chamber apparatus, we
      investigated the nature of the K+ channels involved in basal, cAMP- and Ca2+
      stimulated anion secretion, as reflected by the transepithelial short circuit
      current (I(sc)). The non-specific K+ channel inhibitor Ba2+ inhibited the basal
      I(sc) by either 77 or 16 % when applied directly to the basolateral or apical
      membranes, respectively, indicating that a basolateral K+ conductance is required
      for maintenance of basal anion secretion. Using the K+ channel blockers clofilium
      and clotrimazole, we found basal I(sc) to be sensitive to clofilium, with a small
      clotrimazole-sensitive component. By stimulating the cAMP and Ca2+ pathways, we
      determined that cAMP-stimulated anion secretion was almost entirely abolished by
      clofilium, but insensitive to clotrimazole. In contrast, the Ca2+-stimulated
      response was sensitive to both clofilium and clotrimazole. Thus,
      pharmacologically distinct basolateral K+ channels are differentially involved in
      the control of anion secretion under different conditions. Isolation of the
      basolateral K+ conductance in permeabilized monolayers revealed a small basal and
      forskolin-stimulated I(sc). Finally, using the reverse transcriptase-polymerase
      chain reaction, we found that Calu-3 cells express the K+ channel genes KCNN4 and
      KCNQ1 and the subunits KCNE2 and KCNE3. We conclude that while KCNN4 contributes
      to Ca2+-activated anion secretion by Calu-3 cells, basal and cAMP-activated
      secretion are more critically dependent on other K+ channel types, possibly
      involving one or more class of KCNQ1-containing channel complexes.

PMID- 11826164
TI  - Synaptic transmission in nucleus tractus solitarius is depressed by Group II and
      III but not Group I presynaptic metabotropic glutamate receptors in rats.
AB  - Presynaptic metabotropic glutamate receptors (mGluRs) serve as autoreceptors
      throughout the CNS to inhibit glutamate release and depress glutamatergic
      transmission. Both presynaptic and postsynaptic mGluRs have been implicated in
      shaping autonomic signal transmission in the nucleus tractus solitarius (NTS). We
      sought to test the hypothesis that activation of presynaptic mGluRs depresses
      neurotransmission between primary autonomic afferent fibres and second-order NTS
      neurones. In second-order NTS neurones, excitatory postsynaptic currents (EPSCs)
      synaptically evoked by stimulation of primary sensory afferent fibres in the
      tractus solitarius (ts) and currents postsynaptically evoked by alpha-amino-3
      hydroxy-4-isoxazoleproprionic acid (AMPA) were studied in the presence and
      absence of mGluR agonists and antagonists. Real-time quantitative RT-PCR (reverse
      transcription-polymerase chain reaction) was used to determine whether the genes
      for the mGluR subtypes were expressed in the cell bodies of the primary autonomic
      afferent fibres. Agonist activation of Group II and III but not Group I mGluRs
      reduced the peak amplitude of synaptically (ts) evoked EPSCs in a concentration
      dependent manner while having no effect on postsynaptically (AMPA) evoked
      currents recorded in the same neurones. At the highest concentrations, the Group
      II agonist, (2S,3S,4S)-CCG/(2S,1'S,2'S)-2-carboxycyclopropyl (L-CCG-I), decreased
      the amplitude of the ts-evoked EPSCs by 39 % with an EC50 of 21 microM, and the
      Group III agonist, L(+)-2-amino-4-phosphonobutyric acid (L-AP4), decreased the
      evoked EPSCs by 71 % with an EC50 of 1 mM. mRNA for all eight mGluR subtypes was
      detected in the autonomic afferent fibre cell bodies in the nodose and jugular
      ganglia. Group II and III antagonists ((2S,3S,4S)-2-methyl-2
      (carboxycyclopropyl)glycine (MCCG) and (RS)-alpha-methylserine-O-phosphate
      (MSOP)), at concentrations that blocked the respective agonist-induced synaptic
      depression, attenuated the frequency-dependent synaptic depression associated
      with increasing frequencies of ts stimulation by 13-34 % and 13-19 %,
      respectively (P < 0.05, for each). We conclude that Group II and III mGluRs
      (synthesized in the cell bodies of the primary autonomic afferent fibres and
      transported to the central terminals in the NTS) contribute to the depression of
      autonomic signal transmission by attenuating presynaptic release of glutamate.

PMID- 11826165
TI  - Intrinsic physiological properties of cat retinal ganglion cells.
AB  - Retinal ganglion cells (RGCs) are the output neurons of the retina, sending their
      signals via the optic nerve to many different targets in the thalamus and
      brainstem. These cells are divisible into more than a dozen types, differing in
      receptive field properties and morphology. Light responses of individual RGCs are
      in large part determined by the exact nature of the retinal synaptic network in
      which they participate. Synaptic inputs, however, are greatly influenced by the
      intrinsic membrane properties of each cell. While it has been demonstrated
      clearly that RGCs vary in their intrinsic properties, it remains unclear whether
      this variation is systematically related to RGC type. To learn whether membrane
      properties contribute to the functional differentiation of RGC types, we made
      whole-cell current clamp recordings of RGC responses to injected current of
      identified cat RGCs. The data collected demonstrated that RGC types clearly
      differed from one another in their intrinsic properties. One of the most striking
      differences we observed was that individual cell types had membrane time
      constants that varied widely from approximately 4 ms (alpha cells) to more than
      80 ms (zeta cells). Perhaps not surprisingly, we also observed that RGCs varied
      greatly in their maximum spike frequencies (kappa cells 48 Hz-alpha cells 262 Hz)
      and sustained spike frequencies (kappa cells 23 Hz-alpha cells 67 Hz).
      Interestingly, however, most RGC types exhibited similar amounts of spike
      frequency adaptation. Finally, RGC types also differed in their responses to
      injection of hyperpolarizing current. Most cell types exhibited anomalous
      rectification in response to sufficiently strong hyperpolarization, although
      alpha and beta RGCs showed only minimal, if any, rectification under similar
      conditions. The differences we observed in RGC intrinsic properties were striking
      and robust. Such differences are certain to affect how each type responds to
      synaptic input and may help tune each cell type appropriately for their
      individual roles in visual processing.

PMID- 11826167
TI  - Simultaneous imaging of Ca2+ signals in interstitial cells of Cajal and
      longitudinal smooth muscle cells during rhythmic activity in mouse ileum.
AB  - Electrical rhythmicity in smooth muscle cells is essential for the movement of
      the gastrointestinal tract. Interstitial cells of Cajal (ICC) lie adjacent to
      smooth muscle layers and are implicated as the pacemaker cells. However, the pace
      making mechanism remains unclear. To study the intercellular interaction during
      electrical rhythm generation, we visualized changes in intracellular Ca2+
      concentration ([Ca2+]i) in smooth muscle cells and myenteric ICC within segments
      of mouse ileum loaded with a fluorescent Ca2+ indicator, fluo-3. We observed
      rhythmic [Ca2+]i changes in longitudinal smooth muscle cells travelling rapidly
      through the smooth muscle cell layer. Between the rhythmic Ca2+ transients, we
      found brief Ca2+ transients localized to small areas within smooth muscle cells.
      The amplitude but not the periodicity of rhythmic [Ca2+]i transients in both cell
      types was partially inhibited by nicardipine, an L-type Ca2+ channel antagonist,
      suggesting that the rhythmic [Ca2+]i transients reflect membrane potential
      depolarizations corresponding to both slow waves and triggered Ca2+ spikes.
      Longitudinal smooth muscle cells and myenteric ICC showed synchronous spontaneous
      [Ca2+]i transients in eight out of 21 ileac preparations analysed. In the
      remaining preparations, the synchrony between ICC and smooth muscle cells was
      absent, although the rhythmicity of the smooth muscle cells was not disturbed.
      These results suggest that myenteric ICC may play multiple roles including pace
      making for physiological bowel movement.

PMID- 11826166
TI  - Synaptic connections between layer 4 spiny neurone-layer 2/3 pyramidal cell pairs
      in juvenile rat barrel cortex: physiology and anatomy of interlaminar signalling
      within a cortical column.
AB  - Whole-cell voltage recordings were obtained from 64 synaptically coupled
      excitatory layer 4 (L4) spiny neurones and L2/3 pyramidal cells in acute slices
      of the somatosensory cortex ('barrel' cortex) of 17- to 23-days-old rats. Single
      action potentials (APs) in the L4 spiny neurone evoked single unitary EPSPs in
      the L2/3 pyramidal cell with a peak amplitude of 0.7 +/- 0.6 mV. The average
      latency was 2.1 +/- 0.6 ms, the rise time was 0.8 +/- 0.3 ms and the decay time
      constant was 12.7 +/- 3.5 ms. The percentage of failures of an AP in a L4 spiny
      neurone to evoke a unitary EPSP in the L2/3 pyramidal cell was 4.9 +/- 8.8 % and
      the coefficient of variation (c.v.) of the unitary EPSP amplitude was 0.27 +/-
      0.13. Both c.v. and percentage of failures decreased with increased average EPSP
      amplitude. Postsynaptic glutamate receptors (GluRs) in L2/3 pyramidal cells were
      of the N-methyl-D-aspartate (NMDA) receptor (NMDAR) and the non-NMDAR type. At 
      60 mV in the presence of extracellular Mg2+ (1 mM), 29 +/- 15 % of the EPSP
      voltage-time integral was blocked by NMDAR antagonists. In 0 Mg2+, the
      NMDAR/AMPAR ratio of the EPSC was 0.50 +/- 0.29, about half the value obtained
      for L4 spiny neurone connections. Burst stimulation of L4 spiny neurones showed
      that EPSPs in L2/3 pyramidal cells depressed over a wide range of frequencies (1
      100 s(-1) ). However, at higher frequencies (30 s(-1)) EPSP summation overcame
      synaptic depression so that the summed EPSP was larger than the first EPSP
      amplitude in the train. The number of putative synaptic contacts established by
      the axonal collaterals of the L4 projection neurone with the target neurone in
      layer 2/3 varied between 4 and 5, with an average of 4.5 +/- 0.5 (n = 13 pairs).
      Synapses were established on basal dendrites of the pyramidal cell. Their mean
      geometric distance from the pyramidal cell soma was 67 +/- 34 microm (range, 16
      196 microm). The results suggest that each connected L4 spiny neurone produces a
      weak but reliable EPSP in the pyramidal cell. Therefore transmission of signals
      to layer 2/3 is likely to have a high threshold requiring simultaneous activation
      of many L4 neurons, implying that L4 spiny neurone to L2/3 pyramidal cell
      synapses act as a gate for the lateral spread of excitation in layer 2/3.

PMID- 11826169
TI  - Delayed and prolonged effects of a near threshold EPSP on the firing time of
      human alpha-motoneurones.
AB  - In order to investigate the effects of near-threshold excitatory inputs on the
      precise timing of the action potentials during the tonic discharge of human
      motoneurones, the activity of single motor units was recorded in the extensor
      carpi radialis muscles while tendon taps (indentation, 0.1 mm; duration, 1 ms)
      were being delivered irregularly at a mean rate of 0.8 s(-1). New methods of
      analysis, such as the phase response function, were used to study the relative
      changes in the interspike interval (ISI1) during which the stimulus was being
      delivered and in the three subsequent intervals (ISI2, ISI3, ISI4) as a
      percentage of the pre-stimulus interspike interval (ISI0). The consistency of the
      effects of the actual stimulus as regards the spontaneous variability was
      assessed by comparing the data with those obtained with virtual stimulation. When
      the stimulus occurred at the end of ISI1, and triggered a spike, ISI1 and ISI3
      were generally shortened, whereas ISI2 was lengthened, probably due to the
      negative correlation induced by the summation of the after-hyperpolarisations
      (AHPs). When the stimulus occurred in the middle of ISI1 without triggering a
      spike, ISI1, ISI2 and more rarely ISI3 were shortened. Lastly, when the stimulus
      occurred during the AHP scoop in ISI1, ISI2 was shortened although ISI1 remained
      unchanged. ISI4 was not consistently affected in any of these cases. The present
      results show that the tendon tap-induced inputs (probably from muscle spindle
      primary endings) mediated delayed and prolonged shortening effects of the ISIs on
      most of the alpha-motoneurones tested (n = 16). These effects undetected in
      classic peri-stimulus histogram analysis may involve long-lasting conductance
      changes although the contribution of polysynaptic pathways cannot be excluded.
      The changes in ISI were quite moderate (< 15% of ISI) but highly consistent.
      Their functional involvement in the synchronisation or desynchronisation
      processes and/or the mechanisms of optimisation of muscle contraction still
      remains to be explored.

PMID- 11826168
TI  - Protein kinase A cascade regulates quantal release dispersion at frog muscle
      endplate.
AB  - Uniquantal endplate currents (EPCs) were recorded simultaneously at the proximal,
      central and distal parts of the frog neuromuscular synapse, and their minimal
      synaptic latencies, latency dispersions and sensitivity to noradrenaline, cAMP
      and protein kinase A inhibition were measured. The latency dispersion was highest
      in the proximal part (P90 = 1.25 ms); it decreased to P90 = 0.95 ms in the
      central part and to P90 = 0.75 ms (60 % of the proximal part) in the distal part.
      In the proximal parts of the long neuromuscular synapse, stimulation-evoked EPCs
      with long release latencies were eliminated when the intracellular cAMP was
      increased by beta1 activation by noradrenaline, by the permeable analogue db
      cAMP, by activation of adenylyl cyclase or by inhibition of cAMP hydrolysis. This
      makes the evoked release more compact, and the amplitude of the reconstructed
      multiquantal currents increases. Protein kinase A is a target of this regulation,
      since a specific inhibitor, Rp-cAMP, prevents the action of cAMP in the proximal
      parts and increases the occurrence of long-latency events in the distal parts of
      the synapse. Our results show that protein kinase A is involved in the timing of
      quantal release and can be regulated by presynaptic adrenergic receptors.

PMID- 11826170
TI  - Electrophysiologically distinct smooth muscle cell subtypes in rat conduit and
      resistance pulmonary arteries.
AB  - Pulmonary arteries (PAs), particularly those of the rat, demonstrate a prominent
      voltage-gated K+ (Kv) current (I(Kv)), which plays an important role in the
      regulation of the resting potential. No detailed characterization of
      electrophysiological and pharmacological properties of I(Kv), particularly in
      resistance PA myocytes (PAMs), has been performed. The aim of the present study
      was therefore to compare I(Kv) in rat conduit and resistance PAMs using the
      standard patch clamp technique. We found that 67% of conduit PAMs demonstrated a
      large, rapidly activating I(Kv) which was potently blocked by 4-aminopyridine (4
      AP; IC50, 232 microM), but was almost insensitive to TEA (18% block at 20 mM).
      Thirty-three percent of cells exhibited a smaller, more slowly activating I(Kv)
      which was TEA sensitive (IC50, 2.6 mM) but relatively insensitive to 4-AP (37%
      block at 20 mM). These currents (termed I(Kv1) and I(Kv2), respectively)
      inactivated over different ranges of potential (V(0.5) = -20.2 vs. -39.1 mV,
      respectively). All resistance PAMs demonstrated a large, rapidly activating and
      TEA-insensitive K+ current resembling I(Kv1) (termed I(KvR)), but differing
      significantly from it with respect to 4-AP sensitivity (IC50, 352 microM),
      activation rate, and inactivation potential range (V(0.5), -27.4 mV). Thus, cells
      from conduit PAMs fall into two populations with respect to functional I(Kv)
      expression, while resistance arteries uniformly demonstrate a third type of
      I(Kv). Comparison of the properties of the native I(Kv) with those of cloned Kv
      channel currents suggest that I(Kv1) and I(KvR) are likely to be mediated by
      Kv1.5-containing homo/heteromultimers, while I(Kv2) involves a Kv2.1 alpha
      subunit.

PMID- 11826171
TI  - Propionate-induced relaxation in rat mesenteric arteries: a role for endothelium
      derived hyperpolarising factor.
AB  - Short chain fatty acids, including propionate, are generated in the caecum and
      large intestine, and when absorbed may elicit localised increases in intestinal
      blood flow. We sought to assess the mechanism by which propionate caused
      vasorelaxation. Propionate-mediated relaxation of noradrenaline-preconstricted
      rat mesenteric small arteries (RMSAs, i.d. 200-300 microm) was studied using
      small vessel myography. Propionate (1-30 mM) produced a concentration-dependent
      relaxation. Relaxation induced by 10 mM propionate (the approximate EC50) was
      almost abolished by endothelial denudation, although a marked relaxation to a
      very high concentration of propionate (50 mM) persisted in the absence of the
      endothelium. In endothelium-intact RMSAs, relaxation to 10 mM propionate was
      almost abolished by elevating [K+]o to 25 mM, but was unaffected by 100 microM
      N(omega)-nitro-L-arginine methyl ester (L-NAME) (68 +/- 4 vs. 66 +/- 3% in
      controls, n = 35), or by 1 microM indomethacin (60 +/- 4 vs. 61 +/- 7 % in
      controls, n = 15). In the presence of L-NAME, relaxation to 10 mM propionate was
      significantly and markedly (i.e. > 50 %) inhibited by 50 microM Ba2+ and by the
      combination of 100 nM charybdotoxin and 100 nM apamin. A similar effect on
      propionate-mediated relaxation was also exerted by 100 microM ouabain, and by the
      combination of 50 microM barium with ouabain. Relaxation was also significantly
      and markedly inhibited by pre-treatment of RMSAs with 100 nM thapsigargin or 10
      microM cyclopiazonic acid (CPA). The results demonstrate that 10 mM propionate
      relaxes RMSAs via endothelium-derived hyperpolarising factor (EDHF). The
      observation that relaxation by propionate is inhibited by thapsigargin and CPA
      suggests that this action of propionate involves the release of endothelial cell
      Ca2+ stores.

PMID- 11826172
TI  - Coupling of vasopressin-induced intracellular Ca2+ mobilization and apical
      exocytosis in perfused rat kidney collecting duct.
AB  - Arginine vasopressin (AVP) regulates the osmotic water permeability of the kidney
      collecting duct by inducing exocytotic insertion of aquaporin-2 into apical
      membrane. The coupling between AVP-induced intracellular Ca2+ mobilization and
      apical exocytosis was investigated in isolated perfused rat inner medullary
      collecting duct (IMCD) segments using confocal fluorescence microscopy. Changes
      of [Ca2+]i in IMCD cells were measured with fluo-4. A novel confocal imaging
      technique using a styryl dye, FM1-43, was developed to monitor real-time
      exocytosis induced by arginine vasopressin. AVP (0.1 nM) triggered a rapid
      increase of [Ca2+]i in IMCD cells, followed by sustained oscillations.
      Ratiometric measurement of [Ca2+]i confirmed that the observed [Ca2+]i
      oscillation was a primary event and was not secondary to changes in cell volume.
      The frequencies of [Ca2+]i oscillations in each IMCD cell were independent and
      time variant. 1-Deamino-8-D-arginine vasopressin (a V2 receptor agonist, 0.1 nM)
      simulated the effects of AVP by triggering [Ca2+]i oscillations. In the absence
      of extracellular Ca2+, ryanodine (0.1 mM) inhibited AVP-induced Ca2+
      mobilization. AVP (0.1 nM) triggered accumulative apical exocytosis in IMCD cells
      within 20 s after application. Pre-incubating the IMCD with an intracellular Ca2+
      chelator, BAPTA, prevented AVP-induced intracellular Ca2+ mobilization, apical
      exocytosis, and increase of osmotic water permeability. These results indicate
      that AVP, via the V2 receptor, triggers a calcium signalling cascade observed as
      [Ca2+]i oscillations in the IMCD and that intracellular Ca2+ mobilization is
      required for exocytotic insertion of aquaporin-2.

PMID- 11826173
TI  - Dominance of pressure natriuresis in acute depressor responses to increased renal
      artery pressure in rabbits and rats.
AB  - Increasing renal artery pressure (RAP) activates pressure diuresis/natriuresis
      and inhibits renal renin release. There is also evidence that increasing RAP
      stimulates release of a putative depressor hormone from the renal medulla,
      although this hypothesis remains controversial. We examined the relative roles of
      these antihypertensive mechanisms in the acute depressor responses to increased
      RAP in anaesthetized rabbits and rats. In rabbits, an extracorporeal circuit was
      established which allows RAP to be set and controlled without direct effects on
      systemic haemodynamics. When RAP was maintained at approximately 65 mmHg, cardiac
      output (CO) and mean arterial pressure (MAP) did not change significantly. In
      contrast, when RAP was increased to approximately 160 mmHg, CO and MAP fell 20 +/
      5 % and 36 +/- 5 %, respectively, over 30 min. Urine flow also increased more
      than 28-fold when RAP was increased. When compound sodium lactate was infused
      intravenously at a rate equal to urine flow, neither CO nor MAP fell
      significantly in response to increased RAP. In 1 kidney-1 clip hypertensive rats,
      MAP fell by 54 +/- 10 mmHg over a 2 h period after unclipping. In rats in which
      isotonic NaCl was administered intravenously at a rate equal to urine flow, MAP
      did not change significantly after unclipping (-14 +/- 9 mmHg). Our results
      suggest that the depressor responses to increasing RAP in these experimental
      models are chiefly attributable to hypovolaemia secondary to pressure
      diuresis/natruresis. These models therefore appear not to be bioassays for
      release of a putative renal medullary depressor hormone.

PMID- 11826174
TI  - Reduced glycogen availability is associated with an elevation in HSP72 in
      contracting human skeletal muscle.
AB  - To test the hypothesis that a decrease in intramuscular glycogen availability may
      stimulate heat shock protein expression, seven men depleted one leg of muscle
      glycogen the day before performing 4-5 h of exhaustive, two-legged knee extensor
      exercise at 40 % of leg peak power output. Subjects then rested for a further 3
      h. Muscle biopsies were obtained from the depleted and control leg before,
      immediately after and 3 h into recovery from exercise. These samples were
      analysed for muscle glycogen, and HSP72 gene and protein expression. In addition,
      catheters were placed in one femoral artery and both femoral veins and blood was
      sampled from these catheters prior to exercise and at 1 h intervals during
      exercise and into recovery for the measurement of arterial-venous differences in
      serum HSP72. Plasma creatine kinase (CK) was also measured from arterial blood
      samples. Pre-exercise muscle glycogen content was 40 % lower in the depleted
      compared with the control leg and this difference was maintained throughout the
      experiment (P < 0.05; main treatment effect). Neither HSP72 gene nor protein
      expression was different pre-exercise. However, both HSP72 gene and protein
      increased (P < 0.05) post-exercise in the depleted leg, but not in the control
      leg. Exercise did not increase plasma CK concentrations and we were unable to
      detect HSP72 in the serum of any samples. These results demonstrate that while
      acute, concentric exercise is capable of increasing HSP72 in human skeletal
      muscle, it does so only when glycogen is reduced to relatively low levels. Hence,
      our data suggest that HSP72 protein expression is related to glycogen
      availability. In addition, because CK did not increase and we found no evidence
      of HSP72 in the venous effluent, our data suggest that skeletal muscle is
      impermeable to HSP72.

PMID- 11826175
TI  - A novel algorithm to remove electrical cross-talk between surface EMG recordings
      and its application to the measurement of short-term synchronisation in humans.
AB  - Pairs of discharges of single motor units recorded in the same or different
      muscles often show synchronisation above chance levels. If large numbers of units
      are synchronous within and between muscles then the synchrony will be measurable
      in population recordings such as surface EMG. Measuring synchrony between surface
      EMG recordings has a number of practical and scientific advantages compared with
      single motor units recorded from intramuscular electrodes. However, the
      measurement of such synchrony in the time domain between surface EMGs is
      complicated because the recordings are contaminated by electrical cross-talk. In
      this study we recorded surface EMG simultaneously from five hand and forearm
      muscles during a precision grip task. Using a novel 'blind signal separation'
      algorithm, we were able to remove electrical cross-talk. The cross-talk-corrected
      EMGs could then be used to assess task-dependent modulation in both oscillatory
      (15-30 Hz) and non-oscillatory synchrony (all other frequencies). In agreement
      with previous studies, the oscillatory component was maximal during steady
      holding but abolished during movement. By contrast, the non-oscillatory component
      of the EMG synchrony appeared remarkably constant throughout all phases of the
      task. We conclude that surface EMG recordings can be of considerable use in the
      assessment of population synchrony changes, providing that electrical cross-talk
      between nearby channels is removed using a statistical signal processing
      technique. Our results show a striking difference in the task-dependent
      modulation of oscillatory and non-oscillatory synchrony between muscles during a
      dynamic precision grip task.

PMID- 11826176
TI  - Low intensity exercise in humans accelerates mitochondrial ATP production and
      pulmonary oxygen kinetics during subsequent more intense exercise.
AB  - We undertook this study to determine whether low intensity exercise (55 %
      (O2,max) would significantly alter the metabolic and ventilatory responses
      observed during 10 min of subsequent moderate intensity exercise (75 % (O2,max).
      By executing this work, we hoped to further our understanding of the mechanisms
      that limit mitochondrial ATP production at the onset of exercise. Seven healthy
      human subjects performed 10 min of moderate intensity exercise in the presence
      and absence of 10 min of low intensity exercise, which preceded the moderate
      intensity exercise by 3 min. Muscle biopsy samples were obtained from the vastus
      lateralis at pre-determined time points and oxygen consumption kinetics were
      determined at rest and during low and moderate intensity exercise. Following low
      intensity exercise and 3 min of passive recovery, muscle lactate and
      acetylcarnitine concentrations were elevated above basal levels, but (O2) had
      returned to the resting rate. When moderate intensity exercise was preceded by
      low intensity exercise, there was a significant sparing of phosphocreatine (PCr,
      approximately 25 %, P < 0.05) and reductions in glucose 6-phosphate (G-6-P,
      approximately 50 %, P < 0.05) and lactate (approximately 50 %, P < 0.05)
      accumulation during the first minute of moderate intensity exercise. No
      differences were observed after 10 min of moderate intensity exercise. The (O2)
      on-kinetic response over the first minute of moderate intensity exercise was
      accelerated when preceded by low intensity exercise. Collectively, our results
      suggest the lag in the oxidative ATP delivery at the onset of moderate intensity
      exercise can be overcome by prior low intensity exercise. Furthermore, our
      findings support the view that this lag is at least in part attributable to a
      limitation in acetyl group delivery/availability at the onset of exercise, rather
      than delayed oxygen supply.

PMID- 11826177
TI  - Tachycardia evoked by disinhibition of the dorsomedial hypothalamus in rats is
      mediated through medullary raphe.
AB  - Activation of neurons in the region of the dorsomedial hypothalamus (DMH) appears
      to generate the sympathetically mediated tachycardia seen in experimental stress
      in rats. The purpose of this study was to assess the role of neurons in the area
      of the medullary raphe pallidus (RP) in the tachycardia caused by stimulation of
      the DMH. The cardiovascular response to microinjection of the GABA(A) receptor
      antagonist bicuculline methiodide (BMI) 10 pmol (100 nl)(-1) into the DMH was
      assessed before, and after, injection of the GABA(A) receptor agonist muscimol 80
      pmol (100 nl)(-1) or saline vehicle 100 nl into the RP in urethane-anaesthetized
      rats. Tachycardia evoked by microinjection of BMI into the DMH was mimicked by
      microinjection of BMI 30 pmol (75 nl)(-1) into the RP. This DMH-induced
      tachycardia was markedly suppressed after injection of muscimol into the RP, but
      the response was unaffected by injection of saline into the same region. Thus,
      DMH-induced tachycardia is mediated through activation of neurons in the area of
      the RP, suggesting that these neurons may play a previously unrecognized role in
      stress-induced cardiac stimulation.

PMID- 11826178
TI  - Life-long impairment of hypoxic phrenic responses in rats following 1 month of
      developmental hyperoxia.
AB  - Hypoxic ventilatory and phrenic responses are reduced in adult rats (3-5 months
      old) exposed to hyperoxia for the first month of life (hyperoxia treated). We
      previously reported that hypoxic phrenic responses were normal in a small sample
      of 14- to 15-month-old hyperoxia-treated rats, suggesting slow, spontaneous
      recovery. Subsequent attempts to identify the mechanism(s) underlying this
      spontaneous recovery of hypoxic phrenic responses led us to re-evaluate our
      earlier conclusion. Experiments were conducted in two groups of aged Sprague
      Dawley rats (14-15 months old) which were anaesthetized, vagotomized,
      neuromuscularly blocked and ventilated: (1) a hyperoxia-treated group raised in
      60 % O2 for the first 28 postnatal days; and (2) an age-matched control group
      raised in normoxia. Increases in minute phrenic activity and integrated phrenic
      nerve amplitude (integral Phr) during isocapnic hypoxia (arterial partial
      pressures of O2, 60, 50 and 40 +/- 1 mmHg) were greater in aged control (n = 15)
      than hyperoxia-treated rats (n = 11; P < or = 0.01). Phrenic burst frequency
      during hypoxia was not different between groups. To examine the central
      integration of carotid chemoafferent inputs, steady-state relationships between
      carotid sinus nerve (electrical) stimulation frequency and phrenic nerve activity
      were compared in aged control (n = 7) and hyperoxia-treated rats (n = 7). Minute
      phrenic activity, integral Phr and burst frequency were not different between
      groups at any stimulation frequency between 0.5 and 20 Hz. Carotid body
      chemoreceptor function was examined by recording whole carotid sinus nerve
      responses to cessation of ventilation or injection of cyanide in aged control and
      hyperoxia-treated rats. Electrical activity of the carotid sinus nerve did not
      change in five out of five hyperoxia-treated rats in response to stimuli that
      evoked robust increases in carotid sinus nerve activity in five out of five
      control rats. Estimates of carotid body volume were lower in aged hyperoxia
      treated rats (4.4 (+/- 0.2) x 10(6) microm3) compared to controls (17.4 (+/- 1.6)
      x 10(6) microm3; P <0.01). We conclude that exposure to hyperoxia for the first
      month of life causes life-long impairment of carotid chemoreceptor function and,
      consequently, blunted phrenic responses to hypoxia.

PMID- 11826179
TI  - Prenatal nicotine exposure increases apnoea and reduces nicotinic potentiation of
      hypoglossal inspiratory output in mice.
AB  - We examined the effects of in utero nicotine exposure on postnatal development of
      breathing pattern and ventilatory responses to hypoxia (7.4 % O2) using whole
      body plethysmography in mice at postnatal day 0 (P0), P3, P9, P19 and P42.
      Nicotine delayed early postnatal changes in breathing pattern. During normoxia,
      control and nicotine-exposed P0 mice exhibited a high frequency of apnoea (f(A))
      which declined by P3 in control animals (from 6.7 +/- 0.7 to 2.2 +/- 0.7 min(-1))
      but persisted in P3 nicotine-exposed animals (5.4 +/- 1.3 min(-1)). Hypoxia
      induced a rapid and sustained reduction in f(A) except in P0 nicotine-exposed
      animals where it fell initially and then increased throughout the hypoxic period.
      During recovery, f(A) increased above control levels in both groups at P0. By P3
      this increase was reduced in control but persisted in nicotine-exposed animals.
      To examine the origin of differences in respiratory behaviour, we compared the
      activity of hypoglossal (XII) nerves and motoneurons in medullary slice
      preparations. The frequency and variability of the respiratory rhythm and the
      envelope of inspiratory activity in XII nerves and motoneurons were
      indistinguishable between control and nicotine-exposed animals. Activation of
      postsynaptic nicotine receptors caused an inward current in XII motoneurons that
      potentiated XII nerve burst amplitude by 25 +/- 5 % in control but only 14 +/- 3
      % in nicotine-exposed animals. Increased apnoea following nicotine exposure does
      not appear to reflect changes in basal activity of rhythm or pattern-generating
      networks, but may result, in part, from reduced nicotinic modulation of XII
      motoneurons.

PMID- 11826180
TI  - Regional brain blood flow and cerebral hemispheric oxygen consumption during
      acute hypoxaemia in the llama fetus.
AB  - Unlike fetal animals of lowland species, the llama fetus does not increase its
      cerebral blood flow during an episode of acute hypoxaemia. This study tested the
      hypothesis that the fetal llama brain maintains cerebral hemispheric O2
      consumption by increasing cerebral O2 extraction rather than decreasing cerebral
      oxygen utilisation during acute hypoxaemia. Six llama fetuses were surgically
      instrumented under general anaesthesia at 217 days of gestation (term ca 350
      days) with vascular and amniotic catheters in order to carry out
      cardiorespiratory studies. Following a control period of 1 h, the llama fetuses
      underwent 3 x 20 min episodes of progressive hypoxaemia, induced by maternal
      inhalational hypoxia. During basal conditions and during each of the 20 min of
      hypoxaemia, fetal cerebral blood flow was measured with radioactive microspheres,
      cerebral oxygen extraction was calculated, and fetal cerebral hemispheric O2
      consumption was determined by the modified Fick principle. During hypoxaemia,
      fetal arterial O2 tension and fetal pH decreased progressively from 24 +/- 1 to
      20 +/- 1 Torr and from 7.36 +/- 0.01 to 7.33 +/- 0.01, respectively, during the
      first 20 min episode, to 16 +/- 1 Torr and 7.25 +/- 0.05 during the second 20 min
      episode and to 14 +/- 1 Torr and 7.21 +/- 0.04 during the final 20 min episode.
      Fetal arterial partial pressure of CO2 (P(a,CO2), 42 +/- 2 Torr) remained
      unaltered from baseline throughout the experiment. Fetal cerebral hemispheric
      blood flow and cerebral hemispheric oxygen extraction were unaltered from
      baseline during progressive hypoxaemia. In contrast, a progressive fall in fetal
      cerebral hemispheric oxygen consumption occurred during the hypoxaemic challenge.
      In conclusion, these data do not support the hypothesis that the fetal llama
      brain maintains cerebral hemispheric O2 consumption by increasing cerebral
      hemispheric O2 extraction. Rather, the data show that in the llama fetus, a
      reduction in cerebral hemispheric metabolism occurs during acute hypoxaemia.

PMID- 11826181
TI  - The cutaneous uptake of atmospheric oxygen contributes significantly to the
      oxygen supply of human dermis and epidermis.
AB  - It has been known since 1851 that atmospheric oxygen is taken up by the human
      epidermis. The contribution to total respiration is negligible. Until now the
      significance for the local oxygen supply of the skin has remained unknown. With a
      newly developed sensor, the oxygen fluxoptode, it has become possible to make
      local measurements of the transcutaneous oxygen flux (tcJ(O2)). In this study the
      sensor was calibrated so that absolute values of tcJ(O2) could be reported. At
      rest, tcJ(O2) was determined on normal, humidified skin on the volar forearm of
      20 volunteers of different age groups. In order to evaluate the contribution of
      the blood flow to the oxygen supply of the skin, tcJ(O2) was recorded at the end
      of a 5 min suprasystolic occlusion of the forearm. At normal skin surface partial
      oxygen pressure (163 +/- 9 Torr), tcJ(O2) was 0.53 +/- 0.27 ml O2 min(-1) x m(
      2). A 5 min interruption of blood flow resulted in an increase of 9.5 +/- 6.3 %
      in tcJ(O2). The value of tcJ(O2) was unaffected by the age of the subject.
      Published data on the oxygen diffusion properties of skin and simulations of
      intracutaneous profiles of oxygen partial pressure indicated that under these
      conditions, the upper skin layers to a depth of of 0.25-0.40 mm are almost
      exclusively supplied by external oxygen, whereas the oxygen transport of the
      blood has a minor influence. As a consequence, a malfunction in capillary oxygen
      transport cannot be the initiator of the development of superficial skin defects
      such as those observed in chronic venous incompetence and peripheral arterial
      occlusive disease.

PMID- 11826182
TI  - Distribution and behaviour of glabrous cutaneous receptors in the human foot
      sole.
AB  - To document the activity of cutaneous mechanoreceptors in the glabrous skin of
      the foot sole, tungsten microelectrodes were inserted through the popliteal fossa
      and into the tibial nerve of thirteen healthy human subjects. A total of 104
      cutaneous mechanoreceptors were identified in the glabrous skin of the foot. This
      sample consisted of 15 slow adapting type I (14 %), 16 slow adapting type II (15
      %), 59 fast adapting type I (57 %), and 14 fast adapting type II units (14 %).
      The location of the receptors and the outline of the receptive fields were
      determined by using nylon monofilaments perpendicularly applied against the
      surface of the skin. This revealed that the receptors were widely distributed
      without an accumulation of receptors in the toes. There were also larger
      receptive fields predominantly isolated on the plantar surface of the metatarsal
      tarsal region of the foot sole. Furthermore, with the foot in an unloaded
      position, there was no background discharge activity in any of the cutaneous
      receptors in the absence of intentionally applied stimulation. These findings
      suggest that skin receptors in the foot sole behave differently from those
      receptors found on the glabrous skin of the hand. This may reflect the role of
      foot sole skin receptors in standing balance and movement control.

PMID- 11826183
TI  - Chronic myeloid leukemia: a minimalistic view of post-therapeutic monitoring.

PMID- 11826185
TI  - Core biopsies can be used to distinguish differences in expression profiling by
      cDNA microarrays.
AB  - The primary focus of this work was to determine the feasibility of obtaining
      representative expression array profiles from clinical core biopsies. For this
      purpose we performed six 16-gauge needle core biopsies and an excision biopsy on
      each of two different human xenografts, one from an Ewing's sarcoma cell line and
      the second from neuroblastoma cell line grown in Beige-Scid mice. Three of the
      six core biopsies were processed separately and the remaining three were pooled
      and processed together. As the initial RNA material isolated from the core
      biopsies was not sufficient for microarray analysis, an amplification procedure
      using a modified Eberwine protocol was performed, and the amplified products
      applied onto a 6000-feature human cDNA microarray. Comparisons of the array
      results from core biopsies (amplified RNA) and surgical specimens (non-amplified
      RNA) showed maintenance of the expression profile as assessed by hierarchical
      clustering. Gene expression profiles obtained from microarray analysis clearly
      differentiated the Ewing's sarcoma from the neuroblastoma with both core and
      excisional biopsies as starting material. Pooling the core biopsies did not
      improve the concordance with excisional biopsies. In conclusion, our results
      suggest that core biopsies can be used as a suitable and reliable material for
      the determination of tumor genetic profiles.

PMID- 11826186
TI  - Lymphoid tissues from patients with infectious mononucleosis lack monoclonal B
      and T cells.
AB  - In typical cases of infectious mononucleosis (IM), lymphoid tissue is rarely
      submitted for pathological examination. When lymphoid tissues from IM cases are
      examined, the histological appearance of IM may be difficult to distinguish from
      malignant lymphoma. The purpose of this study was to address the utility of
      clinical molecular assays for T and B cell clonality in distinguishing IM from
      lymphoid malignancy. DNA was recovered from paraffin-embedded archival lymphoid
      tissues of 18 cases of IM and 13 control cases representing other reactive
      lymphoid hyperplasias. T cell receptor gamma (TCR-gamma) and immunoglobulin heavy
      chain (IgH) gene rearrangements were assayed using our standard clinical
      polymerase chain reaction procedures targeting each of the four functional
      variable (V) families and the three joining (J) families of the TCR-gamma gene,
      and framework III of the IgH gene, respectively. In 17 of 18 cases of IM, no
      monoclonal T or B cell populations were detectable. One case, the only spleen
      specimen in the study, had an oligoclonal pattern of TCR-gamma rearrangements.
      The control cases representing other reactive hyperplasias also lacked
      monoclonality. The assays used were sensitive to clonal populations as small as
      5% of cells. In this case series, no monoclonal lymphoid populations were
      identified in any case of IM. This finding suggests that molecular studies are
      useful in distinguishing IM from lymphoid neoplasms.

PMID- 11826184
TI  - Molecular diagnostics in preimplantation genetic diagnosis.

PMID- 11826187
TI  - Molecular diagnosis of clear cell sarcoma: detection of EWS-ATF1 and MITF-M
      transcripts and histopathological and ultrastructural analysis of 12 cases.
AB  - Clear cell sarcoma (CCS), also known as melanoma of soft parts, is an uncommon
      deep soft tissue tumor presenting typically in the lower extremities of young
      adults. Previous cytogenetic studies have established the specificity of the
      recurrent t(12;22)(q13;q12), resulting in a EWS-ATF1 fusion, for CCS. The
      prevalence of the EWS-ATF1 fusion in CCS remains unclear, since most genetically
      confirmed CCS have been reported as isolated cytogenetic or molecular diagnostic
      case reports. We therefore studied histologically confirmed CCS from 12 patients
      for the presence of EWS-ATF1 by reverse-transcriptase polymerase chain reaction
      (RT-PCR), using RNA extracted from either frozen (four cases) or formalin-fixed
      paraffin-embedded (eight cases) material. All primary tumors were located in the
      deep soft tissues of the extremities. Histologically, 10 cases had a typical
      epithelioid nested appearance. Most or all cases showed immunostaining for HMB45
      (12 of 12), S-100 protein (10 of 12), and MITF (12 of 12). Ultrastructural
      analysis showed melanosomes in six of seven cases. The presence of an EWS-ATF1
      fusion transcript was identified by RT-PCR in 11 of 12 cases (91%), all of which
      showed the same fusion transcript structure, namely the previously described in
      frame fusion of EWS exon 8 to ATF1 codon 65. RT-PCR analysis for the melanocyte
      specific splice form of the MITF transcript was positive in all cases tested (4
      of 4). These data confirm that EWS-ATF1 detection can be used as a highly
      sensitive diagnostic test for CCS and that CCS expresses the melanocyte-specific
      form of the MITF transcript, further supporting its genuine melanocytic
      differentiation.

PMID- 11826188
TI  - Spinal muscular atrophy genetic testing experience at an academic medical center.
AB  - Approximately 94% of spinal muscular atrophy (SMA) patients lack both copies of
      SMN1 exon 7. We report our SMA genetic testing experience (total 1281 cases),
      using SMA linkage analysis (32 families), SMA diagnostic testing by PCR-RFLP
      (restriction fragment length polymorphism) to detect the homozygous absence of
      SMN1 exon 7 (and exon 8) (533 cases), and an assay to determine copy number of
      SMN1 exon 7 (SMN1 gene dosage analysis) (716 cases). SMN1 gene dosage analysis is
      used for SMA carrier testing as well as for the confirmation of a heterozygous
      SMN1 deletion in symptomatic individuals who do not lack both copies of SMN1. We
      conclude that comprehensive SMA testing, including SMN1 deletion analysis, SMN1
      gene dosage analysis, and linkage analysis, offers the most complete evaluation
      of SMA patients and their families.

PMID- 11826190
TI  - The evolution of tumor biology: seeking a balance between gene expression
      profiling and morphology studies.

PMID- 11826189
TI  - Detection of SYT-SSX fusion transcripts in archival synovial sarcomas by real
      time reverse transcriptase-polymerase chain reaction.
AB  - Synovial sarcomas comprise approximately 5% of soft tissue sarcomas and occur
      primarily in young adults. The t(X;18) (p11.2;q11.2) has been demonstrated to be
      highly characteristic of synovial sarcomas, and the resulting SYT-SSX fusion
      transcripts have been shown to be useful diagnostic markers. We have developed a
      real-time, reverse transcriptase-polymerase chain reaction (RT-PCR) multiplex
      assay for the identification of the primary fusion transcript types (SYT-SSX1 and
      SYT-SSX2) from formalin-fixed, paraffin-embedded (FFPE) tissues. Twenty-nine of
      30 (96.7%) histologically diagnosed FFPE synovial sarcomas were positive for the
      presence of either the SYT-SSX1 or SYT-SSX2 fusion transcripts. Ten of 16 (62.5%)
      and five of 16 (31.25%) monophasic fibrous synovial sarcomas were positive for
      SYT-SSX1 and SYT-SSX2, respectively. One of 16 (6.25%) monophasic fibrous
      synovial sarcomas was negative for either SYT-SSX fusion transcript. Twelve of 14
      (85.7%) and 2 of 14 (14.3%) biphasic synovial sarcomas were positive for SYT-SSX1
      and SYT-SSX2, respectively. All 13 non-synovial sarcomas tested were negative for
      SYT-SSX1 and SYT-SSX2 fusion transcripts. This method is a relatively simple and
      rapid procedure for the detection of the t(X;18)(p11.2;q11.2).

PMID- 11826191
TI  - 2001 Association for Molecular Pathology annual meeting.

PMID- 11826192
TI  - Can regionalization decrease the number of deaths for children who undergo
      cardiac surgery? A theoretical analysis.
AB  - OBJECTIVE: The association between high case volumes and better patient outcomes
      has been demonstrated for many surgical procedures and medical treatments,
      including surgery for children with congenital heart disease. To simulate the
      effects of regionalization of pediatric cardiac surgery, we assessed the impact
      of reducing the number of pediatric cardiac centers on surgical mortality and
      patient's travel distance. METHODS: This study used abstracted statewide hospital
      discharge data from California from 1995 to 1997. Case volume and in-hospital
      mortality for pediatric cardiac surgeries at each hospital were calculated. All
      hospitals that performed > or =10 pediatric cardiac surgeries in 1995 to 1997
      were included in the analysis. To simulate regionalization, we "closed" the
      hospital with the lowest case volume and redistributed patients from this
      hospital to the nearest remaining hospitals. The number of in-hospital deaths was
      then recalculated using the original mortality rate of each remaining hospital
      multiplied by its new case volume. A multivariate logistic regression was
      conducted to determine the odds ratios of mortality of various types of surgery
      compared with closure of ventricular septal defect. This result was used for
      adjusting for the case-mix of the hospitals. Regionalization simulation analysis
      was repeated, and the number of deaths was recalculated using this adjustment of
      hospital case-mix. We also examined the increase in travel distance of patients
      to the hospitals as a result of the regionalization simulation. RESULTS: In
      California, 6592 children underwent cardiac surgeries in 1995 to 1997 with 352 in
      hospital deaths (overall mortality rate: 5.34%). A quadratic regression model
      demonstrated that a high surgical volume was associated with a low mortality
      rate. We found demarcations between low- and medium-volume hospitals at 70 cases
      per year and medium- and high-volume hospitals at 170 cases per year. With
      adjustment for hospital case-mix, we found that 41 deaths could be avoided when
      all patients from low-volume hospitals were referred, and 83 deaths could be
      avoided when all patients from low- and medium-volume hospitals were referred to
      high-volume hospitals (overall mortality rate decreased to 4.08%). The average
      travel distance for pediatric cardiac surgery was 45.4 miles, which increased by
      12.7 miles when all surgeries were referred to high-volume hospitals. When only
      the 733 high-risk patients were referred from low- and medium-volume hospitals to
      high-volume hospitals, 49 deaths could be avoided, yielding an overall mortality
      rate of 4.60%. CONCLUSIONS: Theoretical regionalization of pediatric cardiac
      surgery is associated with a reduction in surgical mortality from 5.34% to 4.08%
      when all cases were referred to high-volume hospitals, or decrease to 4.60% when
      high-risk cases were referred. Although regionalization is associated with an
      important decrease in the number of deaths, it also increases the travel distance
      for patients. Additional studies on the costs and benefits of regionalization are
      needed to determine the best strategies to improve outcomes for children who
      undergo cardiac surgery.

PMID- 11826193
TI  - Pediatric residents' career intentions: data from the leading edge of the
      pediatrician workforce.
AB  - OBJECTIVE: To determine factors influencing career choices by pediatric residents
      and how they may change the future pediatric physician workforce. BACKGROUND:
      Societal norms and policy decisions can influence the demographics of residents
      entering pediatric practice and resident career choices. Although predictors of
      physician career choice have been identified retrospectively by examining the
      characteristics of physicians in practice, little work has focused on the job
      selection factors important to pediatric residents when they make their
      postresidency career decisions. DESIGN/METHODS: For 3 consecutive years (1997
      1999), the American Academy of Pediatrics surveyed a national sample of 500 third
      year residents, totaling 1500 residents. Data on resident characteristics, job
      selection attitudes, and career decisions were obtained, and trends for the past
      3 years were examined. RESULTS: The percentage of residents intending to practice
      primary care remained constant at around 69% from 1997 through 1999. Female
      residents, US medical graduates, and residents married to nonphysicians were more
      likely to report primary care practice as their future clinical goal. These
      relationships were mediated by higher rates of a primary care practice goal among
      those who felt geographic location and future colleagues were very important and
      by lower rates among those who felt acceptable income, teaching opportunities,
      and research opportunities were very important. Six percent of residents entering
      general pediatrics were heading to rural locations. CONCLUSIONS: With a projected
      increase in the number of female pediatricians and a decline in international
      medical graduates, our study suggests that pediatrics may continue to shift
      toward an increased proportion of general pediatricians. Lifestyle issues are a
      major factor influencing job choice and must be addressed.

PMID- 11826194
TI  - A 16-year neonatal/pediatric extracorporeal membrane oxygenation transport
      experience.
AB  - OBJECTIVE: To characterize the population and survival of neonatal and pediatric
      patients transported by Wilford Hall Medical Center (WHMC) on extracorporeal
      membrane oxygenation (ECMO) since 1985. STUDY DESIGN: A retrospective chart,
      literature, and database review of pediatric and neonatal patients transported on
      ECMO by the WHMC ECMO transport team. In addition, a subpopulation analysis was
      performed comparing neonates with meconium aspiration syndrome (MAS) placed on
      ECMO at WHMC with those infants with MAS transported on ECMO. Characteristics of
      interest for this comparison included disease severity before ECMO, age at
      initiation of ECMO, survival, ECMO-related complications, and duration of ECMO
      support. RESULTS: Forty-two patients transported on ECMO were identified: 23
      neonatal respiratory cases (survival 57%), 7 pediatric respiratory cases
      (survival 71%), 4 cardiac cases (survival 50%), and 8 extra-institutional ECMO
      transports (survival 63%). In the MAS subpopulation, there was significantly
      greater survival in the in-house group--97% (31/32)--than in the ECMO transport
      group--75% (9/12); there were no other significant differences between these
      groups. Overall, no ECMO-related complications leading to patient demise could be
      identified in the ECMO transport group. CONCLUSIONS: ECMO transport, although
      demonstrating acceptable survival, is a risk-laden modality that should not
      replace early referral to an ECMO center.

PMID- 11826195
TI  - Infant weight gain and childhood overweight status in a multicenter, cohort
      study.
AB  - OBJECTIVE: To determine whether a rapid rate of weight gain in early infancy is
      associated with overweight status in childhood. DESIGN: Prospective, cohort study
      from birth to age 7 years. SETTING: Twelve sites across the United States.
      PARTICIPANTS: Twenty-seven thousand, eight hundred ninety-nine (27 899) eligible
      participants born at full term between 1959 and 1965. MAIN OUTCOME MEASURE:
      Overweight status at age 7 years, defined by a body mass index above the 95th
      percentile of the Centers for Disease Control and Prevention reference data.
      RESULTS: In the 19 397 participants with complete data (69.6%), the prevalence of
      overweight status at age 7 years was 5.4%. The rate of weight gain during the
      first 4 months of life (as 100 g/month) was associated with being overweight at
      age 7 years, after adjustment for several confounding factors: odds ratio: 1.38;
      95% confidence interval: 1.32-1.44. This association was present in each birth
      weight quintile, and remained significant after adjustment for the weight
      attained at age 1 year (odds ratio: 1.17; 95% confidence interval: 1.11-1.24).
      CONCLUSIONS: A pattern of rapid weight gain during the first 4 months of life was
      associated with an increased risk of overweight status at age 7 years,
      independent of birth weight and weight attained at age 1 year. These findings may
      lead to new hypotheses regarding the cause of childhood obesity, which may
      contribute to our understanding of this increasing public health problem in the
      United States.

PMID- 11826196
TI  - A prospective investigation into the epidemiology of in-hospital pediatric
      cardiopulmonary resuscitation using the international Utstein reporting style.
AB  - OBJECTIVE: Data regarding pediatric in-hospital cardiopulmonary resuscitation
      (CPR) have been limited because of retrospective study designs, small sample
      sizes, and inconsistent definitions of cardiac arrest and CPR. The purpose of
      this study was to prospectively describe and evaluate pediatric in-hospital CPR
      with the international consensus-derived epidemiologic definitions from the
      Utstein guidelines. METHODS: All 129 in-hospital CPRs during 12 months at a 122
      bed university children's hospital in Sao Paulo, Brazil, were described and
      evaluated using Utstein reporting guidelines. These guidelines include
      standardized descriptions of hospital variables, patient variables, arrest/event
      variables, and outcome variables. CPR was defined as chest compressions and
      assisted ventilation provided because of cardiac arrest or because of severe
      bradycardia with poor perfusion. Outcome variables included sustained return of
      spontaneous circulation, 24-hour survival, 30-day survival, 1-year survival, and
      neurologic status of survivors by the Pediatric Cerebral Performance Category
      Scale. RESULTS: Of the 6024 children admitted to the hospital, 176 (3%) had an
      episode that met the criteria for provision of CPR and 129 (2%) received CPR, 86
      for clinical cardiac arrest and 43 for bradycardia with poor perfusion. Most of
      the children (71%) had preexisting chronic diseases. The most common
      precipitating causes were respiratory failure (61%) and shock (29%). The initial
      cardiac rhythm was asystole in 71 children (55%), pulseless electrical activity
      in 12 (9%), ventricular fibrillation in 1, and bradycardia with pulses and poor
      perfusion in 43 (33%). Eighty-three children (64%) attained sustained return of
      spontaneous circulation (>20 minutes), 43 (33%) were alive at 24 hours, 24 (19%)
      were alive at 30 days, and 19 (15%) were alive at 1 year. Although many factors
      correlated with 24-hour survival, multivariate logistic regression analysis
      revealed independent association of 24-hour survival with respiratory failure as
      the precipitating cause (odds ratio [OR]: 4.92; 95% confidence interval [CI]:
      1.73-14.0), bradycardia with pulses as the initial event (OR: 2.68; 95% CI: 1.01
      7.1), and shorter duration of CPR (OR: 0.92; 95% CI: 0.89-0.96 for each elapsed
      minute). Similarly, 30-day survival was independently associated with respiratory
      failure as the precipitating cause and shorter duration of CPR. Thirty-day
      survival decreased by 5% with each elapsed minute of CPR. Nineteen (91%) of the
      21 survivors to hospital discharge and 16 (83%) of the 19 1-year survivors had no
      demonstrable long-term change in neurologic function from their pre-CPR status.
      CONCLUSIONS: During this study, CPR was uncommon but not rare. Respiratory
      failure was the most common precipitating cause, followed by shock. Preexisting
      chronic diseases were prevalent among these children. Asystole was the most
      common initial cardiac rhythm, and bradycardia with pulses and poor perfusion was
      the second most common. Ventricular fibrillation was rare, but children with
      acute cardiac diseases, such as cardiac surgery and acute cardiomyopathies, were
      not admitted to this children's hospital. CPR was effective: nearly two thirds of
      these children were initially successfully resuscitated, and one third were alive
      at 24 hours compared with imminent death without CPR and advanced life support.
      Nevertheless, survival progressively decreased over time, generally as a result
      of the underlying disease process. One-year survival was 15%. Importantly, most
      of these survivors had no demonstrable change in gross neurologic function from
      their pre-CPR status.

PMID- 11826197
TI  - Risk factors for severe respiratory syncytial virus infection among Alaska native
      children.
AB  - OBJECTIVE: The incidence of hospitalization for respiratory syncytial virus (RSV)
      infection among Alaska Native children is much higher than among non-Native
      populations in the United States. We conducted this study to better understand
      factors associated with hospitalization attributable to RSV infection in this
      high-risk population. DESIGN: Case-control study, including collection of cord
      blood for RSV-neutralizing antibody measurement. SETTING: Remote region of
      southwest Alaska served by 1 regional hospital and 2 referral hospitals.
      SUBJECTS: Case-patients identified through surveillance for RSV infection and
      matched control subjects without acute respiratory infection hospitalization.
      RESULTS: Breastfeeding was associated with a lower risk of RSV hospitalization
      (odds ratio: 0.34), whereas underlying medical conditions (primarily prematurity)
      were associated with increased risk (odds ratio: 6.25). Environmental factors
      associated with a higher risk of hospitalization included household crowding (4
      or more children in the household and crowding index > or =2). The level of
      maternal RSV-neutralizing antibody was not associated with the risk of
      hospitalization. CONCLUSIONS: In this region with extremely high risk of RSV
      hospitalization, several measures, such as encouraging breastfeeding and reducing
      household crowding, could reduce the risk of hospitalization attributable to RSV.

PMID- 11826198
TI  - Decreased morning serum cortisol levels in children with asthma treated with
      inhaled fluticasone propionate.
AB  - OBJECTIVE: In an observational long-term study, we followed 62 children (37
      males, 25 females; mean age: 11.6 +/- 2.9 years) with moderate-to-severe asthma
      for 2 years and studied the effects of fluticasone propionate (176-1320
      microg/day) on the function of the hypothalamic-pituitary-adrenal axis. STUDY
      DESIGN: Morning cortisol levels were monitored after patients had been on
      fluticasone for a mean of 8.0 +/- 5.2 months. Patients who had abnormal low
      morning cortisol levels (<5.5 microg/dL) were then switched either to lower
      fluticasone dosage or to other inhaled steroid formulation. Exact methods based
      on the binomial distribution were used to construct a 95% confidence interval for
      the true proportion of abnormal readings among those treated, and the Wilcoxon
      signed rank test was used to test for a significant difference between cortisol
      levels taken before and after the switch. RESULTS: Twenty-two patients (36%) had
      abnormal morning cortisol levels while on fluticasone. Of the patients on a low
      dose (176 microg/day), 17% had abnormal values, whereas 43% of patients on a high
      dose (> or =880 microg/day) were abnormal. Patients with abnormal results (17/22)
      had their morning cortisol levels repeated 3 months after the switch. Thirteen of
      these patients (77%) had normal levels. A stratified analysis of the difference
      in morning cortisol levels before and after the switch showed significant
      increase in morning cortisol levels in the group receiving 440 microg/day or less
      of fluticasone (median difference: 5.25; confidence interval: 3.60-8.15), as well
      as in the group receiving 440 microg/day or more (median difference: 3.85;
      confidence interval: 1.00-7.60). CONCLUSION: Inhaled fluticasone, even at
      conventional doses, may have greater effects on the adrenal function than
      previously recognized, but the clinical significance of this suppression still
      remains to be established.

PMID- 11826200
TI  - Use of hymenal measurements in the diagnosis of previous penetration.
AB  - OBJECTIVE: To determine the usefulness of measurements of the vaginal opening and
      amount of hymenal tissue present inferiorly and laterally in the diagnosis of
      vaginal penetration. METHODS: The transhymenal diameters and the amount of tissue
      present between the hymenal edge and vestibule inferiorly at 6 o'clock and
      laterally at 3 o'clock and 9 o'clock were measured from photographs of 189
      prepubertal children with a validated history of digital or penile penetration
      and 197 children who denied previous sexual abuse. Statistical analyses were
      conducted to compare the mean values and hymenal symmetry between groups as well
      as to determine the sensitivity and specificity of various cutoff points.
      RESULTS: Comparison of the mean diameters demonstrated that children with a
      penetration history had a significantly larger transverse opening than nonabused
      children when examined in the knee-chest position (5.6 vs 4.6 mm). However, there
      was extensive overlap in measurements between the 2 groups. No significant
      differences were noted between groups in the size of the vertical diameter, the
      amount of tissue present inferiorly or laterally, or the symmetry of the hymen in
      either position. Children with previous penetration were more likely than
      nonabused children to have a horizontal opening measuring >6.5 mm in the knee
      chest position, but the sensitivity and specificity of this test were low (29%
      and 86%, respectively). Higher values had better specificity but very low
      sensitivity. Less than 1.0 mm of hymenal tissue was detected at 6 o'clock only in
      those with a history of penetration (100% specificity), but the sensitivity was
      low (1%-2%). CONCLUSION: Most hymenal measurements lack adequate sensitivity or
      specificity to be used to confirm previous penetration. Less than 1.0 mm of
      hymenal tissue at 6 o'clock was detected only in victims of abuse, but the
      usefulness of this test is limited by the rarity of this finding.

PMID- 11826199
TI  - A longitudinal assessment of thyroid hormone concentrations in preterm infants
      younger than 30 weeks' gestation during the first 2 weeks of life and their
      relationship to outcome.
AB  - OBJECTIVE: This trial examined the effects of triiodothyronine (T3) and
      hydrocortisone on lung disease. We present here the placebo data as this provides
      a natural history of thyroid hormone changes in this group of very preterm
      infants. We also examined the relationship between thyroid hormone levels and the
      outcome death and ventilator dependence at 2 weeks. METHODS: Plasma-free T3
      (FT3), free thyroxine (FT4), total T3, total T4, and thyroid-stimulating hormone
      were measured prospectively in preterm infants who were <30 weeks' gestation
      during the first 14 days of life. The data were obtained from the placebo arm of
      a multicenter, randomized, double-blind, clinical trial of T3 and hydrocortisone,
      called the THORN Trial. RESULTS: A total of 128 infants were recruited into the
      placebo group. The mean FT3 level at <5 hours of age was 4.9 pmol/L and remained
      below this level. FT4 levels decreased from 15 pmol/L to 9.7 pmol/L at 7 days and
      then increased to 11.0 pmol/L by day 14. Total T3 and total T4 levels fell after
      5 hours of age and reached a minimum on day 3. Thyroid-stimulating hormone levels
      fell markedly from 9.2 mU/L to 1.8 mU/L at 72 hours and then increased to
      approximately 4 mU/L. We found that all thyroid hormones but particularly FT3 and
      FT4 hormones were highly significantly related to outcome. The lower the hormone
      levels, the worse the outcome (death or ventilator dependence at 2 weeks of age).
      CONCLUSION: 1) Thyroid hormone levels in preterm infants <30 weeks were much
      lower than in term infants, 2) the postnatal surge of thyroid hormones normally
      seen at 24 to 48 hours of age in term infants did not occur in our group of
      preterm infant, and 3) low FT3 and FT4 levels are associated with higher
      mortality and severity of lung disease.

PMID- 11826201
TI  - Risk reduction in pediatric procedural sedation by application of an American
      Academy of Pediatrics/American Society of Anesthesiologists process model.
AB  - OBJECTIVE: Guidelines for risk reduction during procedural sedation from the
      American Academy of Pediatrics (AAP) and the American Society of
      Anesthesiologists (ASA) rely on expert opinion and consensus. In this article, we
      tested the hypothesis that application of an AAP/ASA-structured model would
      reduce the risk of sedation-related adverse events. METHODS: Prospectively coded
      sedation records were abstracted by a hospital quality improvement specialist
      with practical and administrative experience in pediatric sedation. Process
      variables included notation of nulla per os (NPO) status, performance of a guided
      risk assessment, assignment of ASA physical status score, obtaining informed
      consent, generation of a sedation plan, and assessment of sedation level using a
      quantitative scoring system. Content variables included adherence to AAP NPO
      guidelines, ASA class, target sedation level, actual sedation level, age,
      procedure, and drugs used. Complication risk was assessed by logistic regression
      and Mantel-Haenszel odds ratios (OR). RESULTS: Complications were identified in
      40 of 960 records (4.2%). The complication rate was 34 of 895 (3.8%) with planned
      conscious sedation and 6 of 65 (9.2%) with planned deep sedation ([DS]; OR: 2.6).
      Complications were reduced by performance of structured risk assessment (OR:
      0.10), adherence to all process guidelines (OR: 0), and avoiding actual DS (OR:
      0.4). The only drug associated with higher risk was chloral hydrate (OR: 2.1).
      Failure to adhere to NPO guidelines did not increase risk in this assessment;
      however, the adverse event rate was 0 if all process guidelines were followed.
      CONCLUSIONS: Presedation assessment reduces complications of DS. Repeated
      assessment of sedation score reduces the risk of inadvertent DS. The data provide
      direct evidence that AAP/ASA guidelines can reduce the risk of pediatric
      procedural sedation.

PMID- 11826202
TI  - Effect of children on home smoking restriction by inner-city smokers.
AB  - OBJECTIVE: The home is the site of the most significant environmental tobacco
      smoke (ETS) exposure for children. Surveys show that adults, including smokers,
      agree that smoking should be restricted in homes of smokers with children.
      However, in a national survey, only 12.5% of such homes are actually smoke-free.
      This study examined factors associated with home smoking restriction among inner
      city smokers. METHODS: A cross-sectional survey of 598 adult smokers who attended
      an inner-city community health center was conducted. RESULTS: Home smoking
      restriction was reported by 38.2% of all smokers (95% confidence interval [CI]:
      33.6%-42.8%). Univariate analysis showed smoking restriction was positively
      associated with presence of children and of a nonsmoking adult partner in the
      home, intentional limiting of smoking, stages of change, and fewer number of
      cigarettes smoked daily. On multivariate analysis, home smoking restriction was
      more likely with the presence of a child (odds ratio: 2.63; 95% CI: 1.70-4.08)
      and a nonsmoking adult partner (odds ratio: 2.30; 95% CI: 1.32-4.02) in the home.
      CONCLUSIONS: The presence of children and of nonsmoking adults is associated with
      the practice of smoking restriction in the homes of inner-city smokers. These
      findings suggest that inner-city smokers are concerned about health effects of
      ETS on children. Health professionals should target nonsmoking adult members of
      households with children and smokers but no home smoking restriction and
      emphasize the health effects of ETS on children as a motivation for smoking
      parents to limit exposure and to quit smoking.

PMID- 11826203
TI  - Prenatal prediction of pulmonary hypoplasia: clinical, biometric, and Doppler
      velocity correlates.
AB  - OBJECTIVES: To determine the value of pulmonary artery Doppler velocimetry
      relative to fetal biometric indices and clinical correlates in the prenatal
      prediction of lethal lung hypoplasia (LH) in prolonged (>1 week) oligohydramnios.
      METHODS: Forty-two singleton pregnancies with oligohydramnios associated with
      premature rupture of membranes ([PROM]; n = 31) or bilateral renal pathology (n =
      11) were examined using color-coded Doppler ultrasound in a cross-sectional study
      design. Mean gestational age was 28.0 +/- 4.3 weeks (range: 20-36 weeks).
      Thoracic, cardiac, and abdominal circumference and the largest vertical amniotic
      fluid pocket were measured. Pulsed Doppler measurements of the arterial pulmonary
      branches were made at the level of the cardiac 4-chamber view. Diagnosis of LH
      was based on clinical, radiologic, and pathologic criteria. Clinicians were
      blinded to the prenatal measurements. RESULTS: The prevalence of lethal LH was
      43%. In the PROM subset, combination of onset of PROM at <or =20 weeks, duration
      of oligohydramnios at > or =8 weeks, and degree of oligohydramnios at < or =1 cm
      presented the highest clinical prediction rate for lethal LH. For both the total
      group and the PROM subset, the highest prediction rate for lethal LH was
      presented by thoracic circumference/abdominal circumference ratio, peak systolic
      velocity in the proximal branch, and time-averaged and end-diastolic velocity in
      the middle branch of the pulmonary artery. In the PROM subset, the combination of
      all 3 clinical, biometric, and Doppler parameters revealed the most favorable
      combination to predict lethal LH (positive predictive value: 100%; accuracy: 93%;
      and sensitivity: 71%). CONCLUSION: Doppler velocimetry may detect changes in
      pulmonary artery waveforms in the presence of LH but fails to be the ultimate
      test for the prenatal prediction of lethal LH. The best prediction can be
      achieved by combining clinical, biometric, and Doppler parameters.

PMID- 11826204
TI  - Oral rehydration, emergency physicians, and practice parameters: a national
      survey.
AB  - BACKGROUND/OBJECTIVE: Treatment of dehydrating gastroenteritis, a major cause of
      morbidity in children, remains controversial. Practice parameters issued by the
      American Academy of Pediatrics (AAP) recommend oral rehydration therapy (ORT) as
      the preferred treatment for losses from both mild and moderate dehydration. The
      objective of this study was to test the hypothesis that awareness of the AAP
      practice parameters would be associated with a higher rate of use of ORT among
      emergency physicians. METHODS: A national random survey of emergency physicians
      selected from the mailing list of the AAP Section on Emergency Medicine was
      conducted. Respondents were asked about level of awareness of AAP guidelines and
      preferred route of rehydration for scenarios representing mild (< or =5%),
      moderate (6%-9%), and severe (> or =10%) dehydration. Respondents who were very
      familiar with the AAP practice parameters were designated as the familiar group;
      those who were less familiar were designated as the unfamiliar group. Differences
      in proportions of dichotomous variables were tested by chi2 or Fisher exact test
      as appropriate. Univariate logistic regression modeling was used to determine the
      independent influence of awareness of AAP guidelines on the use of ORT. RESULTS:
      A total of 176 physicians responded (73% response rate). Most were board
      certified in 1 or more specialties: pediatrics (89%), pediatric emergency
      medicine (84%), and adult emergency medicine (63%). Median duration of practice
      was 16 years. Thirty-seven percent of respondents were very familiar with the AAP
      practice parameters. In contrast to the unfamiliar group, the familiar group was
      more likely to use ORT in scenarios of mild dehydration (81% vs 66%) and moderate
      dehydration (25% vs 10%). Logistic regression analysis confirmed that this
      familiar group overall was nearly 3 times more likely to use ORT (odds ratio:
      2.85; 95% confidence interval: 2.46-3.24). CONCLUSIONS: This is the first
      national study to establish a relationship between awareness of the AAP practice
      parameters and physician practices in the treatment of dehydration. Emergency
      medicine physicians who were very familiar with the AAP parameters were
      significantly more likely to use ORT. These findings may have important
      implications for future efforts directed at increasing the rate of ORT use and
      for the evaluation of practice parameters in general.

PMID- 11826205
TI  - A randomized trial of moderately early low-dose dexamethasone therapy in very low
      birth weight infants: dynamic pulmonary mechanics, oxygenation, and ventilation.
AB  - OBJECTIVE: Dexamethasone is used in very low birth weight (VLBW) ventilator
      dependent infants to prevent or decrease the severity of chronic lung disease. We
      reported a significant increase in respiratory compliance during a 7-day weaning
      course of moderately early dexamethasone therapy (0.5 mg/kg/d) in VLBW infants,
      along with a shorter duration of mechanical ventilation and O2 supplementation.
      Although 0.5 mg/kg/d has been the most commonly used dose in preterm infants, the
      use of a lower dose of dexamethasone may reduce potential adverse effects of
      steroid therapy. Quantification of dynamic pulmonary mechanics in VLBW infants
      who receive low-dose dexamethasone has not been reported. The objective of this
      study was to compare the effect of 2 dose regimens of dexamethasone on dynamic
      pulmonary mechanics, mean airway pressure (MAP), and fractional inspired oxygen
      concentration (Fio2) in intubated VLBW infants who were at risk for chronic lung
      disease. METHODS: We studied 47 VLBW (birth weight: 550-1290 g; gestational age:
      24-30 weeks) ventilator-dependent infants at 7 to 14 days of age. Twenty-three
      infants were randomized to receive dexamethasone at 0.5 mg/kg/d intravenously for
      3 days (high dose), 0.25 mg/kg/d for 3 days, and 0.1 mg/kg/d during the 7th day;
      24 infants received low-dose dexamethasone as 0.2 mg/kg/d for 3 days and 0.1
      mg/kg/d for 4 days. Respiratory compliance (Crs) and resistance were measured
      before and on days 2, 5, and 7 of dexamethasone therapy. We recorded airway
      pressure, flow, and tidal volume, and mechanical breaths were analyzed. RESULTS:
      Crs significantly increased during dexamethasone therapy in both groups of
      infants when compared with baseline (74% increase in the high-dose group and 66%
      increase in the low-dose group). Dexamethasone increased tidal volume and
      significantly reduced Fio2 and MAP in both groups of infants. A transient
      increase in blood pressure was noted in both groups. CONCLUSIONS: Our findings
      indicate that 1) comparable significant increases in Crs are present in the low
      dose dexamethasone as well as the high-dose dexamethasone groups on days 2, 5,
      and 7 of steroid therapy; and 2) MAP and Fio2 are significantly decreased during
      dexamethasone therapy in both groups of infants. We conclude that low-dose and
      high-dose dexamethasone, as used in this study, have comparable beneficial
      effects on dynamic pulmonary mechanics and subsequently on oxygen requirement and
      applied ventilatory support in VLBW infants.

PMID- 11826206
TI  - Newborn screening program practices in the United States: notification, research,
      and consent.
AB  - OBJECTIVE: To define current practice among US newborn screening programs for
      notification of results, research, and consenting procedures. METHODS: A
      telephone survey of all US newborn screening program supervisors. RESULTS: All 51
      programs participated. All states reported abnormal results to the infant's
      physician, and some also reported to the hospital and parents. Cases with
      abnormal results were tracked to different endpoints but usually (92.1%) at least
      until a follow-up appointment was made. A total of 66.6% of programs can
      communicate with programs in other states; 9.8% enable families to suppress
      reporting of results to the infant's physician. No state has a mechanism for
      parents to prevent results from entering the medical record. Parents or
      physicians who request results are often authenticated by providing their name
      (52.9%). Many programs (45.1%) report only to physicians and require just their
      name (43.5%), an identification number (17.4%), a letter (26.1%), or a parent's
      signature (26.1%). A total of 70.6% retain residual blood samples; of these, only
      8.3% store them completely devoid of patient identifiers. A total of 49.0% of
      programs aggregate data for research. In 16.0% of these, the data are publicly
      available. In 24.0%, researchers obtain approval at their own institution; in
      24.0%, researchers obtain approval through the state laboratory Institutional
      Review Board. In 74.5% of programs, parents are notified but not asked for
      consent before collection of the sample; 19.6% neither notify parents nor obtain
      consent before screening. CONCLUSIONS: There is wide variation in practice among
      the US newborn screening programs. Because the programs collectively manage a
      comprehensive nationwide genomic databank, careful consideration of how
      information technology and high-throughput genomic analysis are used will be
      essential to allow progress in clinical care, public health, and research while
      protecting individual privacy.

PMID- 11826207
TI  - National underascertainment of sudden unexpected infant deaths associated with
      deaths of unknown cause.
AB  - OBJECTIVE: To investigate underascertainment of unexpected infant deaths at the
      national level as a result of probable classification as attributable to unknown
      cause. METHODS: Using linked birth and death certificates for all US birth
      cohorts from 1983-1991 and 1995-1996, we identified 53 470 sudden infant death
      syndrome (SIDS) fatalities, 9071 unintentional injury deaths, 3473 injury deaths
      classified with intentional or suspicious intent, and 8097 deaths with unknown
      underlying cause. For these deaths, we compared relative risks (RRs) for maternal
      and infant variables available on birth certificates known to be predictive of
      SIDS, unintentional injury, and homicides. Variables available on death
      certificates were compared for unlinked and linked records. Factors related to
      state and national management of cases pending final cause determination are
      reviewed. RESULTS: For deaths from unknown cause, rates were consistently high
      among the same risk groups that have been shown to be at increased risk for SIDS,
      unintentional injury, and homicides. For most risk factors, RRs for deaths
      attributable to unknown causes were somewhat lower than for RRs for
      intentional/suspicious injury deaths but higher than for SIDS or unintentional
      injury, indicating combined contributions from all causes. For example, age at
      death from unknown cause includes RRs that more strongly resemble patterns of
      intentional/suspicious injuries than SIDS or unintentional injury. Deaths from
      unknown cause were more likely to occur during the first week of life for
      unattended births occurring outside clinical settings or when birth certificates
      were not found, similar to intentional/suspicious injury deaths. CONCLUSIONS:
      Risk profiles indicate that deaths of unknown cause are likely to represent a
      mixture of unexpected deaths. The process for determination of cause of
      unexpected death affects national underascertainment of SIDS and injury deaths.
      Better coordination among child fatality review teams and local, state, and
      national officials should reduce underascertainment and improve documentation of
      circumstances surrounding deaths for prevention efforts.

PMID- 11826208
TI  - Marijuana: a decade and a half later, still a crude drug with underappreciated
      toxicity.
AB  - In 1984, I published in this journal a review entitled "Marijuana: A Crude Drug
      With a Spectrum of Underappreciated Toxicity." In the introduction to that
      article, I disclosed that our son Keith, who was 15 years old at the time, was in
      a long-term, modified outpatient adolescent drug and alcohol rehabilitation
      program because he had become dependent on marijuana with its associated
      behavioral, interpersonal, scholastic, and antisocial problems. Keith and most of
      his friends had experimented several times with LSD, beer, and several other
      drugs but never used injection drugs. Marijuana was clearly Keith's drug of
      choice and the only drug he used with regularity. Approximately 1 year later,
      Keith graduated from the treatment program. He completed the early aftercare
      component, relapsed several times, and completed a 4-month refresher drug
      rehabilitation program in another state. Nine years after admission to the first
      rehabilitation program, Keith finally attained some adult goals. Now 34 years
      old, he has been drug-free for 10 years. He is the president and owner of a
      successful discount cellular phone business that he started. More important, a
      decade ago, he reestablished an excellent and close relationship with his
      parents. As far as I can tell, Keith remains drug-free except for an occasional
      beer.

PMID- 11826209
TI  - Reimbursement for telephone care.

PMID- 11826210
TI  - Practitioner policies and beliefs and practice immunization rates: a study from
      Pediatric Research in Office Settings and the National Medical Association.
AB  - OBJECTIVE: To identify vaccination policies and beliefs associated with practice
      immunization rates (PIR) among office-based pediatricians. METHODS: Primary care
      pediatricians recruited from the Pediatric Research in Office Settings (PROS)
      network of the American Academy of Pediatrics or the Pediatric Section of the
      National Medical Association abstracted immunization data from a consecutive
      sample of children who were 8 to 35 months old and seen in the office for any
      reason; 1 provider per practice collected this information. PIR were determined
      at 8 and 19 months of age by calculating the percentage of children in the sample
      who were fully immunized at that age. Before collecting the immunization data,
      all practitioners in each participating practice completed a questionnaire
      detailing his or her policies and beliefs regarding the administration of
      vaccines. Part of the questionnaire was a scenario involving a 4-month-old child
      who was due for a diphtheria-tetanus-acellular pertussis immunization at a health
      supervision visit. A list of 13 possible clinical conditions in this hypothetical
      patient were presented; practitioners were asked which of these were a
      contraindication to vaccination. One set of policies and beliefs was computed for
      each practice using a weighted average of the responses of each provider in a
      particular practice. Regression analyses were used to assess the association
      between each policy and belief and PIR at 8 and 19 months, after controlling for
      potentially confounding sociodemographic characteristics. RESULTS: Data were
      analyzed from 112 practices; median PIR at 8 and 19 months were 85% and 71%,
      respectively. The following policies and beliefs were not statistically
      associated with PIR at either 8 or 19 months: use of acute visits for
      vaccinations, conducting an immunization audit within the previous 12 months,
      perceived difficulties in implementing new vaccine recommendations or staying
      informed about new recommendations, conducting practice meetings to discuss
      immunization policies, perception of profitability of providing vaccinations,
      appointment reminders for scheduled visits, and specific tracking mechanisms for
      patients who are due for or behind in immunizations. After controlling for
      sociodemographic characteristics, recommending inactivated poliovirus vaccine and
      having fewer contraindications to vaccination were associated with statistically
      higher PIR at 8 months and 19 months. Increasing the maximum number of injections
      administered at 1 visit was associated with a higher PIR at 8 months but not 19
      months of age. CONCLUSION: Policies and beliefs linked to many official
      recommendations for increasing immunization rates were not associated with higher
      PIR. However, accepting fewer contraindications to vaccination, administering all
      vaccines for which an infant is eligible at each health supervision visit, and
      adopting recommended changes in immunization schedules may help providers fully
      vaccinate a higher percentage of their patients.

PMID- 11826211
TI  - Why we need to know whether prophylactic antibiotics can reduce measles-related
      morbidity.
AB  - In some parts of the world, measles vaccination has resulted in very substantial
      reductions in measles-related morbidity and mortality. Even so, it has been
      estimated that 30 million people still contract the disease every year, that
      nearly 1 million of these die, and that measles-related deaths account for about
      10% of all deaths in children under the age of 5 in developing countries.
      Existing evidence from controlled trials suggests that antibiotic prophylaxis in
      measles can result in important reductions in measles-related morbidity, and, at
      a World Health Organization meeting convened in 1993 to decide on research
      priorities for the treatment of measles, highest priority was accorded to
      additional controlled trials of prophylactic antibiotics. As controlled trials of
      vitamin A in measles have made clear, such trials are feasible. Continued
      acquiescence in uncertainties about the effects of prophylactic antibiotics in a
      disease that continues to afflict so many children worldwide is unacceptable.

PMID- 11826212
TI  - Rapid, competent, and inexpensive developmental-behavioral screening is possible.

PMID- 11826213
TI  - Tools for measuring daily activities in children: promoting independence and
      developing a language for child disability.

PMID- 11826214
TI  - Nifedipine labeling illustrates the pediatric dilemma for off-patent drugs.

PMID- 11826215
TI  - Thrombotic thrombocytopenic purpura attributable to von Willebrand factor
      cleaving protease inhibitor in an 8-year-old boy.

PMID- 11826216
TI  - Ginkgo seed poisoning.
AB  - A 2-year-old girl presented with vomiting and diarrhea 7 hours after eating a
      large quantity of ginkgo seeds. She exhibited an afebrile convulsion 9 hours
      after ingestion. The serum concentration of 4-metoxypyridoxine was as high as 360
      ng/mL. Although reported cases of ginkgo seed poisoning usually involve children
      who exhibit repetitive seizures that can be fatal, prompt administration of
      pyridoxal phosphate (2 mg/kg) may have prevented additional seizures. This is the
      first English-language case report measuring 4-metoxypyridoxine concentration
      during ginkgo seed poisoning. Awareness of the potential danger of
      overconsumption of this traditional food and its prompt treatment with pyridoxal
      phosphate may hasten recovery.

PMID- 11826217
TI  - Follow-up management of children with tympanostomy tubes.
AB  - The follow-up care of children in whom tympanostomy tubes have been placed is
      shared by the pediatrician and the otolaryngologist. Guidelines are provided for
      routine follow-up evaluation, perioperative hearing assessment, and the
      identification of specific conditions and complications that warrant urgent
      otolaryngologic consultation. These guidelines have been developed by a consensus
      of expert opinions.

PMID- 11826218
TI  - Postnatal corticosteroids to treat or prevent chronic lung disease in preterm
      infants.
AB  - This statement is intended for health care professionals caring for neonates and
      young infants. The objectives of this statement are to review the short- and long
      term effects of systemic and inhaled postnatal corticosteroids for the prevention
      or treatment of evolving or established chronic lung disease and to make
      recommendations for the use of corticosteroids in infants with very low birth
      weight. The routine use of systemic dexamethasone for the prevention or treatment
      of chronic lung disease in infants with very low birth weight is not recommended.

PMID- 11826219
TI  - Coparent or second-parent adoption by same-sex parents.
AB  - Children who are born to or adopted by 1 member of a same-sex couple deserve the
      security of 2 legally recognized parents. Therefore, the American Academy of
      Pediatrics supports legislative and legal efforts to provide the possibility of
      adoption of the child by the second parent or coparent in these families.

PMID- 11826220
TI  - Technical report: coparent or second-parent adoption by same-sex parents.
AB  - A growing body of scientific literature demonstrates that children who grow up
      with 1 or 2 gay and/or lesbian parents fare as well in emotional, cognitive,
      social, and sexual functioning as do children whose parents are heterosexual.
      Children's optimal development seems to be influenced more by the nature of the
      relationships and interactions within the family unit than by the particular
      structural form it takes.

PMID- 11826221
TI  - Urine fluorescence: is it a good test for ethylene glycol ingestion?

PMID- 11826222
TI  - BCG vaccination and prevention of allergic disease.

PMID- 11826223
TI  - Continuous subcutaneous glucose monitoring in children with type 1 diabetes.

PMID- 11826224
TI  - Resuscitation--air versus 100% oxygen.

PMID- 11826225
TI  - Positional otitis media and otorrhea after tympanostomy-tube placement.

PMID- 11826226
TI  - Medical concerns in the female athlete.

PMID- 11826227
TI  - Seroprotection rates after late doses of hepatitis B vaccine.

PMID- 11826228
TI  - Pacifier as a risk factor for acute otitis media.

PMID- 11826229
TI  - Xylitol administered only during respiratory infections failed to prevent acute
      otitis media.
AB  - OBJECTIVE: As regular administration of xylitol had been effective in preventing
      acute otitis media (AOM) in children, we tested whether xylitol administered only
      at times of acute respiratory infection (ARI) reduces the occurrence of AOM.
      METHODS: Healthy children (N = 1277) were recruited from child care centers and
      randomized after screening with tympanometry to receive either control mixture (n
      = 212), xylitol mixture (n = 212), control chewing gum (n = 280), xylitol chewing
      gum (n = 286), or xylitol lozenges (n = 287) during an ARI. The trial was
      randomized and double blinded within the mixture and chewing gum groups. The
      parents began administering the products to their children at the onset of
      symptoms of ARI. The follow-up lasted until resolution of the symptoms or up to 3
      weeks. RESULTS: A total of 1253 of the 1277 randomized children were eligible for
      the analysis. Altogether, 980 (78%) of 1253 children had at least 1 episode of
      ARI during the 4 months that the trial lasted. The occurrence of AOM during this
      episode was 34 (20.5%) of 166 in the xylitol mixture group, as compared with 32
      (20.4%) of 157 among the children who received the control mixture. Among the
      older children who received control chewing gum, xylitol chewing gum, or xylitol
      lozenges, AOM was experienced by 24 (11.0%) of 218, 31 (14.1%) of 220, and 34
      (15.5%) of 219, respectively. None of the differences between the groups was
      statistically significant. CONCLUSIONS: Xylitol administered only during an ARI
      was ineffective in preventing AOM.

PMID- 11826230
TI  - Asthma morbidity after the short-term use of ibuprofen in children.
AB  - OBJECTIVE: To test the hypothesis that short-term use of ibuprofen increases
      asthma morbidity in children. METHODS: A randomized, double-blind, acetaminophen
      controlled clinical trial was conducted. Children who had asthma and a febrile
      illness were randomly assigned to receive either acetaminophen suspension or
      ibuprofen suspension for fever control. Rates of hospitalization and outpatient
      visits for asthma during follow-up were compared by randomization group. RESULTS:
      A total of 1879 children receiving asthma medications were studied. Rates of
      hospitalization for asthma did not vary significantly by antipyretic assignment;
      compared with children who were randomized to acetaminophen, the relative risk
      for children who were assigned to ibuprofen was 0.63 (95% confidence interval:
      0.25-1.6). However, the risk of an outpatient visit for asthma was significantly
      lower in the ibuprofen group; compared with children who were randomized to
      acetaminophen, the relative risk for children who were assigned to ibuprofen was
      0.56 (95% confidence interval: 0.34-0.95). CONCLUSIONS: Rather than supporting
      the hypothesis that ibuprofen increases asthma morbidity among children who are
      not known to be sensitive to aspirin or other nonsteroidal antiinflammatory
      drugs, these data suggest that compared with acetaminophen, ibuprofen may reduce
      such risks. Whether the observed difference in morbidity according to treatment
      group is attributable to increased risk after acetaminophen use or a decrease
      after ibuprofen cannot be determined. These data provide evidence of the relative
      safety of ibuprofen use in children with asthma.

PMID- 11826231
TI  - Newborn hepatitis B vaccination policy in hospital nurseries.
AB  - OBJECTIVE: Hepatitis B vaccination (HBV) is unlike any other immunization series
      because it can be initiated in the hospital nursery. The objective of this study
      was to describe how hospital nurseries develop HBV policies and to describe the
      sources of information used for learning about national HBV recommendations.
      METHODS: A cross-sectional telephone survey was conducted on a national random
      sample of nursery medical directors of 290 hospital nurseries representing all 50
      states. The outcomes measured were methods used by hospital nurseries to develop
      HBV policy and sources of information used by nursery directors to learn about
      national HBV recommendations. RESULTS: Directors at 207 (71%) of 290 eligible
      nurseries responded. Of the 184 nurseries that have considered developing an HBV
      policy, the most common method was through a formal committee (43%). In 104 (57%)
      of these nurseries a nurse was involved in policy development, and in 15 (8%) the
      nurse manager initiated the process. The most common source of initial
      information about the July 1999 announcement to suspend the nursery dose of HBV
      was the American Academy of Pediatrics. The most common initial source of
      information about the availability of thimerosal-free HBV was pharmaceutical
      companies. Physician, nurse, and pharmacist colleagues were cited as sources of
      information with similar frequency (12, 11, and 20 cases, respectively).
      CONCLUSIONS: Physicians are not the sole initiators and developers of HBV policy
      in the newborn nursery. Although almost all nurseries designate a physician as a
      nursery director, in many cases (55% of cases) the position is "rotating" or as
      part of another administrative position (63% of cases). Many hospital nurseries
      involve nurses and pharmacists in key roles to stay current with HBV
      recommendations and to develop subsequent policy. Using nonphysician national
      organizations as additional channels of information might expedite dissemination
      about changes in HBV recommendations and, as a result, improve nursery awareness
      and adoption of national HBV guidelines.

PMID- 11826232
TI  - Evaluating acceptability and completeness of overseas immunization records of
      internationally adopted children.
AB  - BACKGROUND: Increasing numbers of families in the United States are adopting
      children who were born in other countries. Appropriate immunization of
      internationally adopted children provides a challenge to pediatricians who must
      evaluate documentation of vaccines administered overseas and fulfill the
      recommended US childhood immunization schedule. The acceptability of vaccinations
      received outside the United States was addressed by the Advisory Committee on
      Immunization Practices in 1994, but few population-based studies assessing these
      vaccinations have been reported. METHODS: We performed a retrospective cohort
      study of 504 children who were adopted from other countries and evaluated in 1997
      and 1998. Our goal was to determine the acceptability of overseas vaccinations
      for meeting US immunization requirements. We assessed immunization records for
      both valid documentation of receipt of vaccine and comparability with the
      recommended US schedule. We also determined the number of children who were up to
      date (UTD) for diphtheria-tetanus-pertussis, polio, hepatitis B, and measles
      mumps-rubella vaccines under the US schedule. RESULTS: The children's mean age at
      initial US evaluation was 19 months; 71% were girls, and most (88%) had resided
      in orphanages. They were adopted from 16 countries, most frequently from China
      (48%) and Russia (31%). Thirty-five percent (178) of children had overseas
      immunization records, 167 (94%) of which were considered valid. Most children
      with valid records (112 [67%] of 167) were UTD for 1 or more vaccine series under
      the US schedule. CONCLUSION: The majority (65%) of internationally adopted
      children had no written records of overseas immunizations. Among the 178 children
      with documented overseas immunizations, 167 (94%) had valid records and some
      vaccine doses that were acceptable and UTD under the US schedule. Additional
      research and more specific guidance in the most cost-effective approaches to
      evaluation of overseas vaccinations are needed to ensure appropriate state-side
      vaccination and to improve the health of these children and their communities.

PMID- 11826233
TI  - Relation of childhood height to obesity among adults: the Bogalusa Heart Study .
AB  - OBJECTIVE: In a previous study of the role of various predictors of adult
      obesity, we found that relatively tall children had a higher body mass index
      (BMI; kg/m2) in early adulthood. In this study, the objective was to determine
      whether childhood height is related to adult adiposity and whether the
      association is independent of childhood levels of BMI and triceps skinfold
      thickness. METHODS: The longitudinal relations of childhood height to relative
      weight and skinfold (sum of subscapular and triceps) thicknesses in adulthood
      were examined in a larger sample (N = 1055) of 2- to 8-year-olds who were
      followed for an average of 18 years. RESULTS: Compared with children whose
      heights were below the gender- and age-specific median, a child with a height-for
      age above the 95th percentile (P) was approximately 2.5 times as likely to have a
      BMI > or =30 kg/m2 and approximately 5 times as likely to have a skinfold sum
      >90th P in adulthood. Although height and adiposity were associated (r = 0.29)
      among children, the observed longitudinal relations persisted after controlling
      for BMI and the triceps skinfold thickness in childhood. For example, among
      children with the same BMI, each 10-cm difference in height was associated with
      differences in adulthood of 0.9 kg/m2 for BMI and 4 mm for the skinfold sum.
      CONCLUSIONS: Although these results need to be confirmed in other studies, it is
      possible that information on childhood height could be used to identify more
      accurately children who are likely to be obese in later life.

PMID- 11826234
TI  - Expression of activation markers and cytokine mRNA by peripheral blood CD4 and
      CD8 T cells in atopic and nonatopic childhood asthma: effect of inhaled
      glucocorticoid therapy.
AB  - HYPOTHESIS: Activated CD8 as well as CD4 T cells contribute to the production of
      asthma-relevant cytokines in both atopic and nonatopic childhood asthma.
      OBJECTIVES: To measure the percentages of peripheral blood CD4 and CD8 T cells
      expressing naive/memory (CD45RA/CD45RO) and activation (HLA-DR, CD25) markers, as
      well as mRNA-encoding interleukin-4 (IL-4) and interleukin-5 (IL-5) in atopic and
      nonatopic childhood asthmatics and in nonasthmatic controls matched for age and
      atopic status; and to study the effects of inhaled glucocorticoid therapy of the
      asthmatics on these measurements. METHODS: Peripheral blood mononuclear cells
      were isolated from 17 atopic and 8 nonatopic stable (not acutely ill) asthmatics
      aged 7 to 16 years with moderate-to-severe disease and from 15 nonasthmatic
      controls matched for age and atopic status. Activation markers on CD4 and CD8 T
      cells were measured by flow cytometry, and expression of cytokine mRNA by in situ
      hybridization with CD4 and CD8 T cells were isolated using magnetic beads.
      Measurements were repeated in 18 of the asthmatics 4 to 6 months after initiation
      or escalation of inhaled glucocorticoid therapy for inadequately controlled
      asthma. RESULTS: The percentages of CD4 T cells expressing CD45RO but not CD45RA
      were elevated in both asthma groups as compared with the relevant controls and
      were reduced in association with de novo or augmented inhaled glucocorticoid
      therapy. The percentages of CD8 T cells expressing both markers were not elevated
      in asthmatics as compared with controls. The percentages of both CD4 and CD8 T
      lymphocytes expressing HLA-DR and CD25 were elevated in the asthmatics as
      compared with controls, and significantly reduced in association with de novo or
      augmented inhaled glucocorticoid therapy. Elevated percentages of CD4 T cells
      expressing mRNA encoding IL-4 and IL-5, and CD8 T lymphocytes expressing IL-5,
      were found in asthmatics as compared with the controls. De novo or augmented
      inhaled glucocorticoid therapy was associated with significant reductions in the
      percentages of CD4 T cells expressing IL-5 and IL-4 mRNA, as well as improvements
      in lung function, symptom scores, and bronchial hyperresponsiveness to
      metacholine (PD20) in both the atopic and nonatopic asthmatics. CONCLUSIONS: The
      data are consistent with the hypothesis that both activated CD4 and CD8 T cells
      are associated with child asthma, and that CD4 T cells make a greater
      contribution to IL-4 and IL-5 synthesis. Increased dosages of inhaled
      glucocorticoid resulted in clinical improvement in the asthmatics along with
      reduced T-cell activation and cytokine mRNA expression, suggesting a possible
      causal association.

PMID- 11826235
TI  - Treatment with highly active antiretroviral therapy in human immunodeficiency
      virus type 1-infected children is associated with a sustained effect on growth.
AB  - INTRODUCTION: Growth failure is a common feature of children with human
      immunodeficiency virus type 1 (HIV-1) infection. Children who are treated with
      mono or dual nucleoside analogue reverse transcriptase inhibitor (NRTI) therapy
      show a temporary increase in weight gain and linear growth rate. In adults,
      protease-inhibitor-containing antiretroviral therapy is associated with a
      sustained weight gain and increased body mass index (BMI). Experience with
      protease inhibitors and growth in children is still limited. The data mainly deal
      with short-term effects on growth. OBJECTIVE: To evaluate the effect of highly
      active antiretroviral therapy (HAART) on growth in children with HIV-1 infection.
      DESIGN AND METHODS: We analyzed selected growth parameters, clinical data, and
      laboratory results as part of a prospective, open, uncontrolled, multicenter
      study to evaluate the clinical, immunologic, and virologic response to HAART
      consisting of indinavir, zidovudine, and lamivudine in children with HIV-1
      infection. Height and weight were measured at 0, 12, 24, 36, 48, 60, 72, 84, and
      96 weeks after initiation of HAART. Information about the children's growth
      before enrollment in the study was retrieved from the hospital medical records
      and/or the school doctor or health center. BMI was calculated. z Scores were used
      to express the standard deviation (SD) in SD units from the Dutch reference
      curves for age and gender. Viral loads and CD4+ T-cell counts were examined
      prospectively and related to these growth parameters. z Scores were also
      calculated for CD4+ T-cell counts to correct for age-related differences. A z
      score of 0 represents the P50, which is exactly the age/sex-appropriate median. A
      height z score of -1 indicates that a child's height is 1 SD below the age- and
      gender-specific median height for the normal population. Virologic responders
      were defined as those who either reached an undetectable viral load (<500
      copies/mL) or had a >1.5 log reduction in viral load compared with baseline at
      week 12 after the initiation of HAART, which was maintained during the follow-up
      period. RESULTS. PATIENTS: Twenty-four patients were included (age: 0.4-16.3
      years at baseline), with a median HIV-1 RNA load of 105 925 copies/mL (5.03 log),
      a median CD4+ T-cell count of 0.586 x 10(9)/L (median z score: -2.28 SD), a
      median height z score of -1.22, a median weight z score of -0.74, and a median
      baseline BMI z score of -0.32. Eleven patients were naive to antiretroviral
      therapy, and 13 patients had received previous treatment with NRTI monotherapy.
      Twenty children used indinavir and 4 children used nelfinavir as part of HAART.
      VIROLOGIC AND IMMUNOLOGIC RESPONSES TO HAART: Seventeen children were virologic
      responders, and 7 children were virologic nonresponders. In patients naive to
      NRTIs, median baseline viral loads were significantly higher than in pretreated
      patients. However, at weeks 48 and 96, there was no significant difference
      between the viral loads of both groups. At baseline, there was no significant
      difference in CD4+a T-cell z scores between virologic responders and
      nonresponders or between naive and pretreated patients. During 96 weeks of HAART,
      the increase of CD4+ T-cell z score was significantly higher in responders than
      in nonresponders. The increase in CD4+ T-cell z score was not significantly
      different for naive and pretreated patients. HEIGHT, WEIGHT, AND BMI z SCORE
      CHANGES: We found that there was a trend toward a significantly increased z score
      change during 96 weeks of HAART compared with the z score change before HAART
      initiation for height and weight, but not for BMI. GROWTH AND VIROLOGIC RESPONSE
      TO HAART: When the data were analyzed separately for virologic responders and
      nonresponders, virologic responders showed significant increases in height and
      weight. The height and weight of virologic nonresponders did not change
      significantly. The BMI did not change significantly in responders or in
      nonresponders. GROWTH AND IMMUNOLOGIC RESPONSE TO HAART: The increase of weight
      and BMI z scores from baseline correlated positively with the CD4+ T-cell z score
      increase from baseline. It did not correlate with absolute CD4+ T-cell count
      increase. Height z score increase did not correlate with CD4+ T-cell z score or
      with absolute CD4+ T-cell counts. GROWTH AND PREVIOUS NRTI TREATMENT: The height
      z score decrease from week -48 to baseline was significantly larger in naive than
      in pretreated patients. The weight and BMI z score change from week -48 to
      baseline was not significantly different for pretreated and naive patients. From
      baseline to week 96, the height and weight z score change increased significantly
      in naive patients but not in pretreated patients compared with the change from
      week -48 to baseline. The BMI z score did not change significantly over 96 weeks
      of HAART for naive or pretreated patients. GROWTH AND CLINICAL STAGE OF
      INFECTION: The clinical stage of infection according to the Centers for Disease
      Control and Prevention classification correlated negatively with the BMI z score
      and the weight z score at baseline but not with the height z score. Thus,
      children with the most severe clinical disease had the lowest BMI and weight z
      scores at baseline. The BMI z score increased more in children with more advanced
      clinical infection at baseline, who had lower BMI at baseline. The clinical stage
      of infection did not correlate with the change in weight z score from baseline to
      week 96. CONCLUSIONS: HAART has a positive influence effect on the growth of HIV
      1-infected children. This effect is sustained for at least 96 weeks. Height and
      weight are favorably influenced in children in whom HAART leads to a reduction of
      the viral load of at least 1.5 log or to <500 copies/mL and to an increase in the
      CD4+ T-cell z score. In contrast to the increase of the BMI in adults on HAART,
      BMI did not increase in all children effectively treated with HAART. BMI
      increased more in children with an advanced stage of infection and a poor
      nutritional status at baseline. Data from pretreated and naive patients were
      difficult to interpret, because the baseline characteristics of these 2 groups
      differed too much.

PMID- 11826236
TI  - Cardiopulmonary manifestations of fulminant enterovirus 71 infection.
AB  - BACKGROUND: The pathogenesis of acute pulmonary edema and cardiac collapse after
      enterovirus 71 (EV71) infection are not completely understood. OBJECTIVE: To
      determine the hemodynamic features and the mechanism of pulmonary edema (PE)
      after EV71 infection by direct intracardiac monitoring. DESIGN: Prospective
      clinical and laboratory study at a tertiary medical center. PARTICIPANTS: Five
      consecutive infants, ages 2 to 13 months, with EV71 infection-proved by viral
      isolation in 4 and antibody in 1-with PE were enrolled. The clinical
      characteristics were systemically assessed. Hemodynamic profiles were determined
      every 4 hours by simultaneously implanted pulmonary arterial and central venous
      catheters during the acute stage. RESULTS: Magnetic resonance imaging revealed
      that all 5 infants had brainstem lesions. All patients had tachycardia and
      hyperthermia. Transient systolic hypertension was noted in 1 patient, and 1
      presented with hypotension. Pulmonary artery pressure in all 5 infants was normal
      or mildly elevated (26-31 mm Hg), and central venous pressure ranged from 10 to
      22 mm Hg. Pulmonary artery occlusion pressures were normal or slightly elevated
      (13-16 mm Hg). Systemic and pulmonary vascular resistances were transiently
      increased in only 1 patient. The stroke volume index decreased to 15.3 to 35.7
      mL/M2 (normal: 30-60 mL/M2), but because of the elevated heart rate, the cardiac
      index did not decrease. All hemodynamics normalized within days. CONCLUSION:
      Fulminant EV71 infection may lead to severe neurologic complications and acute
      PE. The acute PE and cardiopulmonary decompensation in EV71 infection are not
      directly caused by viral myocarditis. The mechanism of PE may be related to
      increased pulmonary vascular permeability caused by brainstem lesions and/or
      systemic inflammatory response instead of increased pulmonary capillary
      hydrostatic pressure.

PMID- 11826237
TI  - Polymerase chain reaction in the diagnosis and prognosis of Mediterranean
      visceral leishmaniasis in immunocompetent children.
AB  - OBJECTIVE: To assess the usefulness of a polymerase chain reaction (PCR) assay
      amplifying the small subunit rRNA coding region of Leishmania species performed
      on peripheral blood (PB) and bone marrow (BM) aspirates for the diagnosis and
      follow-up of visceral leishmaniasis (VL) in children living in the Mediterranean
      basin. DESIGN: A prospective study was conducted on children consecutively
      hospitalized over a 1-year period at our Infectious Diseases Department in Sicily
      (Italy) presenting with fever, hepatosplenomegaly, and/or pancytopenia and a
      positive Leishmania serology (> or =1:40). RESULTS: Among the 14 patients
      hospitalized with signs and symptoms suggestive of the disease and a positive
      serology, we identified 10 cases of Mediterranean VL. PCR performed on PB and BM
      aspirates was positive in all cases and concordant with microscopy and/or culture
      performed on BM. Leishmania DNA was cleared from PB a median of 6 days after the
      start of treatment; during follow-up (median: 9 months; range: 6-12 months) 1
      child relapsed. In this case, BM PCR remained positive with rapid reappearance of
      a positive signal also in PB. CONCLUSIONS: PB PCR allows a rapid and noninvasive
      parasitologic diagnosis of Mediterranean VL among immunocompetent children and is
      at least as sensitive as a diagnosis made on the basis of BM aspirates. The lack
      of disappearance from BM and the reappearance of positive PCR on PB is predictive
      of clinical relapse. Qualitative and semiquantitative PCR may be the standard
      method for monitoring response to therapy in immunocompetent children.

PMID- 11826238
TI  - Bilateral laparoscopic adrenalectomy as a treatment for classic congenital
      adrenal hyperplasia attributable to 21-hydroxylase deficiency.
AB  - OBJECTIVE: Current medical therapy for congenital adrenal hyperplasia (CAH)
      attributable to a complete 21-hydroxylase deficiency is not optimal. Difficulties
      in adequate adrenal androgen suppression are common, causing short adult stature,
      infertility, and hyperandrogenism. We report the use of laparoscopic bilateral
      adrenalectomy as a definitive therapy for this condition and argue that it is
      superior to conventional medical therapy in selected patients. METHODS:
      Participants were 2 adult females with classic, salt-wasting CAH and a history of
      poor adrenal control were selected for adrenalectomy: case 1 was a 22-year-old
      woman with mild hirsutism and primary amenorrhea; case 2 was a 28-year-old woman
      with severe hirsutism, acne, and amenorrhea. Preoperative and postoperative
      hormonal profiles were performed. Both underwent laparoscopic bilateral
      adrenalectomy with a mean follow-up of 37 months. RESULTS: Bilateral laparoscopic
      adrenalectomy was performed in both patients with no complications and an
      uneventful recovery. Maintenance medications of glucocorticoid and
      mineralocorticoid replacement were reduced compared with preoperative doses.
      Three years postoperatively, however, rising adrenal steroid precursor levels in
      case 1, presumably caused by adrenal rests, prompted an increase in replacement
      therapy dose. Hirsutism and acne improved in both patients, and regular
      menstruation began 5 months (case 1) and 2 months (case 2) postoperatively.
      Pregnancy 3 years postoperatively was successful in case 2, who delivered a
      unaffected infant, full-term via Cesarian section. CONCLUSIONS: Surgical
      adrenalectomy should be considered in females with classic CAH attributable to 21
      hydroxylase deficiency and a history of poor hormonal control. Adrenalectomy may
      prove to be superior to current medical therapy for these patients.

PMID- 11826239
TI  - Family income and the impact of a children's health insurance program on reported
      need for health services and unmet health need.
AB  - OBJECTIVE: In an era when expanding publicly funded health insurance to children
      in higher income families has been the major strategy to increase access to
      health care for children, it is important to determine if the benefits to higher
      income children attributable to the receipt of health coverage are similar to
      those observed for lower income children. This study investigated how the likely
      impact of child health insurance expansions varies with family income. METHODS:
      We surveyed parents or guardians of children who were enrolled in a state
      sponsored health insurance program (Massachusetts Children's Medical Security
      Plan [CMSP]) that, before the implementation of the State Children's Health
      Insurance Plan (SCHIP), was open to all children regardless of income. A
      stratified sample of children was drawn from administrative files. We grouped
      children by income category (low-income [LI]: < or =133% of the federal poverty
      limit [FPL], middle-income [MI]: 134%-200% of the FPL, high-income [HI]: >200% of
      the FPL) that corresponded to eligibility for public health insurance programs in
      the state (Medicaid-eligible, SCHIP-eligible, and income that exceeded SCHIP
      eligibility). The majority of telephone interviews were conducted between
      November 1998 and March 1999. The overall response rate was 61.8%, yielding a
      sample of 996 children. The CSMP benefit package included comprehensive coverage
      for preventive and specialty care and limited coverage for ancillary services.
      Children enrolled in CMSP were not covered for inpatient hospital stays but those
      whose family income was <400% of the FPL were eligible to receive full or partial
      coverage for inpatient care through the state's free care pool. Although the CMSP
      benefit package did not meet the standards for a SCHIP, it is an approximate
      equivalent for children with incomes <200% of the FPL, who have full coverage for
      hospitalization through the state's free care pool. We used survey responses to
      develop 2 sets of indicators: the first for reported need for services and the
      second for unmet need or delays in care among children whose parents reported a
      need for the service. Within each set, we created indicators for 5 types of
      service (medical care, dental care, prescription drugs, vision services, and
      mental health care) and an additional composite indicator. The composite
      indicator aggregated all categories of services covered under CMSP in a single
      measure; it included all services except dental services, which, at the time of
      the study, were not covered by the program. The composite indicator served as the
      dependent variable in regression models. We used weighted chi2 tests to identify
      statistically significant differences in reported need and unmet need for the 5
      types of medical services and the aggregate measure of all services covered by
      CMSP. We examined differences across income groups at 2 points in time: during
      the period children were uninsured before enrollment and while enrolled. We used
      weighted logistic regression to assess the independent association of family
      income with our dependent variables: reported need for health services and the
      presence of unmet need, controlling for other covariates. To evaluate the impact
      of participation in a child health insurance program, we examined unmet need
      before and after program enrollment, testing for statistical significance using
      McNemar's test for within-subject changes. RESULTS: During the period of
      uninsurance before enrollment, prescription drugs (70%) was the health service
      needed most frequently, followed by medical (65%) and dental (57%) care. For the
      composite measure of services covered by CMSP, reported need for services was not
      significantly different by income. Need for medical care, dental care, and
      prescription drugs were significantly greater among children who had been
      uninsured for >6 months before enrollment. In addition, a significantly greater
      proportion of adolescent participants needed dental, vision, and mental health
      services than younger enrollees. While enrolled, among recently enrolled
      children, 77% need medical services, 68% prescription drugs, and 59% dental. In
      unadjusted models MI and HI children were more than 2 times as likely to report
      need for covered services as LI children. After adjusting for possible
      confounders, the effect of income was no longer significant. Instead,
      nonadolescents (odds ratio [OR]: 2.44; 95% confidence interval [CI]: 1.25-4.76)
      and children with white ethnicity (OR: 3.03; 95% CI: 1.43-6.67) were
      significantly more likely to report need for services. Before enrollment, unmet
      need among those who reported need for services was 5% for medical, 4%
      prescription drugs, 31% dental, 30% vision, and 33% mental health. For the
      composite measure of services covered by CMSP, LI children were significantly
      more likely to have had unmet need before enrollment than MI and HI children
      (20%, 10%, 7% by income). As compared with younger children, adolescents also had
      significantly greater unmet need for the composite measure (19% vs 10%). In
      multivariate models, not having a usual site of care was a highly significant
      predictor of unmet need or delayed care (OR: 3.41; 95% CI: 1.28-9.11). Ninety
      eight percent of parents cited cost as the reason they had difficulty obtaining
      needed care. After enrollment, the proportion of children who needed care and had
      difficulty obtaining it decreased for all categories of care. Less than 1% of
      enrollees reported unmet need or delays in care for medical services and 3% for
      prescription drugs. Children who needed vision and mental health services
      continued to experience difficulty obtaining these services (17% for each
      category of care), although they were covered as part of the benefit package.
      Unmet need or delays in care for dental services, which at the time of the study
      were not covered under CMSP, remained high (27%). We found a significant
      reduction in unmet need among children in all income groups and no significant
      differences in unmet need by income. Controlling for other covariates,
      adolescents (OR: 3.11; 95% CI: 1.58-6.12) and children with compromised health
      (OR: 3.20; 95% CI: 1.35-7.58) were more likely to have had difficulty obtaining
      needed services while enrolled in the program. Children in larger families (OR:
      0.40; 95% CI: 0.17-0.96) and who were previously uninsured for >6 months (OR:
      0.45; 95% CI: 0.22-7.58) were less likely to have difficulty obtaining care.
      CONCLUSION: Our findings demonstrate the positive impact of providing health
      insurance coverage to children regardless of income. The HI children who enrolled
      in the program looked similar to children with incomes that meet current SCHIP
      eligibility guidelines, suggesting that expansions of SCHIPs to HI children
      should not qualitatively change the program dynamics.

PMID- 11826240
TI  - Serum luteinizing hormone rises within minutes after depot leuprolide injection:
      implications for monitoring therapy.
AB  - OBJECTIVE: To find the time of the serum gonadotropin peak after depot leuprolide
      injection in children and to show that depot leuprolide therapy can be monitored
      by measuring serum luteinizing hormone (LH) immediately after injections. STUDY
      DESIGN: We measured concentrations of leuprolide, LH, and follicle-stimulating
      hormone (FSH) at multiple time points before and after the first dose of depot
      leuprolide in 14 pubertal children beginning therapy. Gonadotropins and sex
      steroids were measured again after the fourth dose. RESULTS: Serum leuprolide,
      LH, and FSH levels rose rapidly after initial injection, reaching sustained
      elevations at 30 to 120 minutes. The median LH level increased from 2.1 mIU/mL at
      baseline to a peak of 27.5 mIU/mL at 45 minutes, and FSH increased from 5.2 to
      16.5 mIU/mL. After 3 months on therapy, median serum LH after depot leuprolide
      injection was only 0.83 mIU/mL, similar to levels observed after intravenous or
      subcutaneous gonadotropin-releasing hormone stimulation in comparable subjects on
      depot leuprolide. CONCLUSION: Our pharmacokinetic data demonstrate that free
      leuprolide present in a depot leuprolide injection is equivalent to gonadotropin
      releasing hormone in stimulating a rapid rise in serum gonadotropin
      concentrations. We propose that a single serum sample for LH obtained 30 to 60
      minutes after depot leuprolide injection in children provides a convenient and
      accurate assessment of treatment efficacy.

PMID- 11826241
TI  - Neuron-specific enolase and S100B in cerebrospinal fluid after severe traumatic
      brain injury in infants and children.
AB  - BACKGROUND: Traumatic brain injury (TBI) is a leading cause of death and
      disability in children. Considerable insight into the mechanisms involved in
      secondary injury after TBI has resulted from analysis of ventricular
      cerebrospinal fluid (CSF) obtained in children with severe noninflicted and
      inflicted TBI (nTBI and iTBI, respectively). Neuron-specific enolase (NSE) is a
      glycolytic enzyme that is localized primarily to the neuronal cytoplasm. S100B is
      a calcium-binding protein localized to astroglial cells. In adults, CSF and serum
      concentrations of NSE and S100B have served as markers of neuronal damage after
      TBI. Neither NSE nor S100B has previously been studied in CSF after TBI in
      infants or children. OBJECTIVE: To compare the time course and magnitude of
      neuronal and astroglial death after nTBI and iTBI by measuring CSF concentrations
      of NSE and S100B using a rapid enzyme-linked immunosorbent assay. METHODS: Severe
      nTBI and iTBI were defined by strict clinical criteria. Serial ventricular CSF
      samples (n = 35) were obtained from children 1.5 to 9 years with severe nTBI (n =
      5) and children 0.2 to 1.5 years (n = 5) with severe iTBI. Lumbar CSF samples
      from 5 children 0.1 to 2.3 years evaluated for meningitis were used as a
      comparison group. CSF NSE and S100B concentrations were quantified by an enzyme
      linked immunosorbent assay (SynX Pharma Inc, Ontario, Canada). RESULTS: There was
      no difference in age between patients with iTBI (median [range]: 0.2 years [0.2
      1.8]), nTBI (2.0 years [1.5-9]), and the comparison group (0.2 years [0.2-1.8]).
      The initial Glasgow Coma Scale score was higher in the iTBI group (9 [4-14])
      versus the nTBI group (3 [3-7]). NSE was increased in TBI versus the comparison
      group in 34 of 35 samples. Mean NSE was markedly increased (mean +/- SEM, 117.1
      +/- 12.0 ng/mL vs 3.5 +/- 1.4 ng/mL). After nTBI, a transient peak in NSE was
      seen at a median of 11 hours after injury (range: 5-20 hours). After iTBI, an
      increase in admission NSE was followed by a sustained and delayed peak at a
      median of 63 hours after injury (range: 7-94). The magnitude of peak NSE was
      similar in nTBI and iTBI. S100B was increased versus the comparison group in 35
      of 35 samples. Mean S100B was markedly increased in TBI versus the comparison
      group (1.67 +/- 0.2 ng/mL vs 0.02 +/- 0.0 ng/mL). S100B showed a single peak at
      27 hours (range: 5-63 hours) after both nTBI and iTBI. The mean S100B
      concentration, peak S100B concentration, and the time to peak were not associated
      with mechanism of injury. CONCLUSIONS: Markers of neuronal and astroglial death
      are markedly increased in CSF after severe nTBI and iTBI. ITBI produces a unique
      time course of NSE, characterized by both an early and late peak, presumably
      representing 2 waves of neuronal death, the second of which may represent
      apoptosis. Delayed neuronal death may represent an important therapeutic target
      in iTBI. NSE and S100B may also be useful as markers to identify occult iTBI,
      help differentiate nTBI and iTBI, and assist in determining the time of injury in
      cases of iTBI.

PMID- 11826242
TI  - Delayed umbilical bleeding--a presenting feature for factor XIII deficiency:
      clinical features, genetics, and management.
AB  - OBJECTIVES: The objectives of this study were 1) to assess the importance of an
      early diagnosis for factor XIII (FXIII) deficiency, and 2) to investigate the
      molecular basis and mechanism(s) of disease in the patients under study. METHODS:
      The case histories of 6 FXIII-deficient patients were examined to assess the
      influence of early versus delayed diagnosis and replacement therapy. The
      nucleotide sequence of the FXIIIA gene was determined to identify the underlying
      mutations responsible for the bleeding diathesis in each patient. Molecular
      modeling was used to predict the mechanism(s) of disease causation for each
      mutation. RESULTS: All cases presented with umbilical hemorrhage. Patients 1 to 3
      were diagnosed, and their prophylactic therapy was commenced in infancy.
      Diagnosis in patients 4 to 6 was considerably delayed and, as a result, they
      continued to suffer from many bleeding symptoms. The FXIIIA gene mutations
      identified in these patients were as follows: a homozygous GAA-->AAA mutation in
      codon 102 (Glu102Lys) in patient 1 and a homozygous AGC-->AGG mutation in codon
      295 (Ser295Arg) in patients 2 to 6. These mutations segregate with disease and
      are absent from the normal population, suggesting that they are likely to be
      disease-causing sequence changes. Computer modeling indicates that both the
      Lys102 and Arg295 mutants are unable to fold correctly, and probably result in
      unstable FXIIIA molecules. CONCLUSIONS: We demonstrate the importance of
      recognizing delayed umbilical hemorrhage as a presenting feature for congenital
      FXIII deficiency, and the value of early diagnosis and prophylaxis. The bleeding
      disorder of patient 1 was attributable to a homozygous Glu102Lys mutation in
      FXIIIA. A homozygous Ser295Arg mutation in FXIIIA was responsible for FXIII
      deficiency in patients 2 to 6.

PMID- 11826243
TI  - Early excess weight gain of children in the Pima Indian population.
AB  - OBJECTIVE: To determine the period of childhood in which weight relative to
      height increases in Pima Indian children and young adults in comparison with the
      general US population. METHODS: Heights and weights of children in the Pima
      Indian population were derived from either clinical examinations conducted by the
      Department of Public Health Nursing (from 1-48 months of age), or from
      examinations in the National Institutes of Health longitudinal survey of health
      in the Pima population (for birth and ages 5-20 years), and compared with
      standards for the US population recently published by the National Center for
      Health Statistics. RESULTS: Weight relative to height (weight-for-length in
      children aged <24 months, body mass index at ages > or =2 years) was
      significantly higher in Pima children at all ages examined after the first month
      of life. Compared with reference values, the most dramatic increases in weight
      relative to height occurred in 2 stages of childhood: mean z scores of weight-for
      length increased between 1 month (mean +/- SEM: males: -0.2 +/- 0.19; females: 
      0.02 +/- 0.14) and 6 months (males: 0.8 +/- 0.04; females: 0.7 +/- 0.04) of age;
      mean z scores for body mass index increased gradually between 2 years (males: 0.4
      +/- 0.06; females: 0.4 +/- 0.08) and 11 years (males: 1.4 +/- 0.08; females: 1.4
      +/- 0.08) and remained stable thereafter. CONCLUSION: Excessive weight gain
      occurs early in the Pima population with changes relative to reference values
      most marked in the first 6 months of life and between 2 and 11 years.
      Interventions toward primary prevention of obesity may need to be targeted at
      children rather than adults in this population.

PMID- 11826244
TI  - Health-related quality of life of children and adolescents after traumatic brain
      injury.
AB  - OBJECTIVE: Relatively little is known about the longer-term impact of traumatic
      brain injury (TBI) on children's daily functioning, especially the broader
      outcome domain referred to as health-related quality of life (HRQL). The
      objective of the present study was to examine the nature and predictors of HRQL
      outcomes in children with moderate to severe TBI an average of 4 years
      postinjury. METHODS: The study used a concurrent cohort-prospective design
      involving postinjury assessments of 3 groups of traumatically injured children
      and their families including 42 with severe TBI, 42 with moderate TBI, and 50
      with orthopedic injuries only. Parent and child perceptions of HRQL and child
      adaptive behavior measures were obtained along with parent descriptions of the
      child's health problems and use of medical and mental health services. Predictors
      included indices of injury severity, social factors, and ratings of preinjury
      child behavior problems and school performance. RESULTS: Based on parent report,
      adolescents who sustained severe TBI had lower HRQL related to overall
      psychosocial functioning and in the domains of behavior, mental health, general
      health, and family impact than adolescents who sustained orthopedic injuries
      only. Communication skills, daily living skills, and general adaptive functioning
      also were rated lower in the severe TBI group. In contrast to parent reports,
      adolescents with severe TBI did not rate their HRQL in most domains differently
      than did adolescents with orthopedic injuries. There were no group differences in
      frequency of persistent physical limitations. Sixty-seven percent of families of
      children with severe TBI used mental health counseling at some point after the
      injury. Risks for poorer HRQL outcomes were related to family social disadvantage
      and poorer preinjury child behavioral and academic functioning. CONCLUSIONS:
      Findings underscore the importance of using comprehensive measures of HRQL, along
      with traditional indicators of functional outcomes, when evaluating the longer
      term impact of injuries in children. Identification of predictors suggests the
      need for close monitoring and intervention of high-risk children.

PMID- 11826245
TI  - The behavioral impact of growth hormone treatment for children and adolescents
      with Prader-Willi syndrome: a 2-year, controlled study.
AB  - INTRODUCTION: Prader-Willi syndrome (PWS) is characterized by obesity, hypotonia,
      hypogonadism, hyperphagia, short stature, and a neurobehavioral profile that
      includes cognitive deficits, learning problems, and behavioral difficulties that
      increase in both quantity and severity over time. PWS results from an alteration
      in the molecular composition of a critical region of C#15q. Morbid obesity
      resulting from hyperphagia is amplified by decreased energy expenditure and
      reduced physical activity. The hyperphagia has proven refractory to all
      psychopharmocologic intervention; the behavioral components are equally resistant
      to psychotropic intervention. PWS patients' body composition resembles that of
      individuals with growth hormone (GH) deficiency, including short stature and
      reduced lean body mass with concomitant increased fat mass. We hypothesized that
      GH administration to children with PWS, in addition to stimulating linear growth,
      would improve body composition, increase energy expenditure and fat utilization,
      and improve muscle strength, physical agility, and pulmonary function. Two recent
      reports from this study document significant positive effects of GH treatment on
      these children's physical parameters measured in a 2-year, controlled study.
      However, the behavioral impact of GH treatment in this population remains
      incompletely described. A psychosocial burden, including emotional, behavioral,
      and cognitive disturbances associated with short stature, has been previously
      described in a non-PWS population with GH deficiency and idiopathic short
      stature. An impaired quality of life and psychosocial status is also documented
      in otherwise normal adults with GH deficiency. In both populations, growth
      hormone replacement therapy (GHRT) is reported to improve alertness, activity
      level, endurance, irritability, tendency to worry, and extroversion resulting in
      better personal relationships with fewer conflicts. This report focuses on that
      portion of the study investigating the behavioral and psychosocial outcomes
      accompanying increased stature and improved physical status for persons with PWS
      treated with GHRT. We hypothesized that, as in other populations, GHRT for
      persons with PWS would have a significant positive effect on their psychosocial
      status as well as an improvement in their growth parameters. METHODS: A 2-year,
      controlled study with control group crossover in the second year was used. Fifty
      four consecutive children with genetically confirmed PWS were enrolled. Patients
      were 4 to 16 years of age at time of enrollment, had skeletal maturation <13 for
      girls and <15 for boys; all but 3 participants remained prepubertal (Tanner stage
      1) throughout the study. Children who had previous therapy with GH were excluded,
      as were children with a scoliosis >20 degrees. After a 6-month growth assessment
      were randomized into a 60:40 treatment:control ratio. Treatment consisted of
      Nutropin (Genentech), 1 mg/m2/day. A modified Offord Survey Diagnostic Instrument
      (SDI) was used to monitor behavior at 6-month intervals. The SDI is a 165-item
      behavioral checklist with items rated on a scale of 0 = Never or Not True, 1 =
      Sometimes or Somewhat True, and 2 = Often or Very True. The items are balanced
      between positively and negatively scored items. The present instrument was
      designed to derive diagnoses for the following Diagnostic and Statistical Manual
      of Mental Disorders, Fourth Edition categories: Depression, Obsessive-Compulsive
      Disorder, Anxiety Disorder, Somatization Disorder, Conduct Disorder, and
      Attention-Deficit/Hyperactivity Disorder. The SDI was modified to include 10
      items specifically inquiring about PWS (eg, denies having PWS, picks excessively
      at skin, nose, or other body parts). Because diagnoses are not mutually
      exclusive, an individual can meet criteria for 1 or more diagnostic categories.
      The SDI contains a second section measuring behavior functioning in the school
      environment, in the family, and in personal and social relationships. A wider
      scoring range is used and is question-specific. Parallel forms of this measure
      are available for parents, teachers, and the child him/herself. We gathered data
      from both parents and teachers at 6-month intervals. No questionnaire was scored
      until the completion of the entire study to avoid any possibility of an
      inadvertent "feedback" or "self-fulfilling prophecy" effect. All questionnaires
      were scored by a Bachelor's level research assistant blind to study assignment.
      Family stress was monitored with the Family Inventory of Life Events. At study
      completion, the impact of GH was measured with a 13-item summary interview
      adapted from Wiren et al. After completion of all final study visits, a single
      research assistant blind to treatment assignment interviewed all families by
      phone. This method was chosen to minimize any positively biased demand
      characteristics. RESULTS: Both between-group and within-group contrasts were
      computed for baseline, 12 (time 1) and 24 month (time 2) measures. Because
      behavioral deterioration, as well as improvement, was a possibility, a 2-tailed
      hypothesis test was used for all comparisons. No differences were found between
      treatment and control groups, nor within groups across measurement points for
      attentional symptoms, anxiety, obsessive-compulsive complex, violence, or
      psychotic symptoms. Similarly, no differences were noted between groups on
      depressive symptoms; however, a significant positive effect (reduction of
      depressive symptoms) was noted for the treatment group from baseline to time 1,
      and was retained at time 2. The group was divided by age, with those 11.0 years
      and younger comprising one group and those older the second group. This analysis
      indicated that the major reduction in depressive symptoms occurred in those over
      11 years old. When divided by age, a second unexpected finding emerged. There was
      a significant increase in attention-deficit/hyperactivity disorder symptoms from
      baseline to 24 months in those children 11 and under, independent of treatment
      status. The groups were subsequently further broken down by sex and by genetic
      status (deletion versus disomy) with no significant findings. At no time was the
      expected behavioral deterioration reported. We conclude that in addition to the
      previously detailed improvements in physical parameters for these children,
      behavioral improvement, including a lack of predictable behavioral deterioration
      during the treatment period, is a strong argument for the use of GHRT for this
      difficult syndrome.

PMID- 11826246
TI  - Functional Independence Measure (WeeFIM) for Chinese children: Hong Kong Cohort.
AB  - BACKGROUND: The Functional Independence Measure (WeeFIM) for children is a simple
      to-administer scale for assessing independence across 3 domains in American
      children. WeeFIM was based on a conceptual framework by the World Health
      Organization (1980) of pathology, impairment, disability and handicap, and the
      "burden of care." WeeFIM is useful in assessing functional independence in
      children aged 6 months to 7 years. It can be used for children with developmental
      disabilities aged 6 months to 21 years. Normative WeeFIM data had been validated
      for American children. Because of cultural and environmental differences among
      countries, normative data for the Chinese population are needed. With a normative
      database, the progression of independence at home and in the community can be
      evaluated. WeeFIM is an 18-item, 7-level ordinal scale instrument that measures a
      child's consistent performance in essential daily functional skills. Three main
      domains (self-care, mobility, and cognition) are assessed by interviewing or by
      observing a child's performance of a task to criterion standards. WeeFIM is
      categorized into 2 main functional streams: "Dependent" (ie, requires helper:
      scores 1-5) and "Independent" (ie, requires no helper: scores 6-7). Scores 1
      (total assistance) and 2 (maximal assistance) belonged to the "Complete
      Dependence" category. Scores 3 (moderate assistance), 4 (minimal contact
      assistance), and 5 (supervision or set-up) belonged to the "Modified Dependence"
      category. Scores 6 (modified independence) and 7 (complete independence) belonged
      to the "Independent" category. The WeeFIM is a 7-level criterion-specific ordinal
      scale. Level 7 requires no assistance for the child and the child completes the
      task independently without requiring a device. During the task, there is no
      concern about safety or taking an inordinate amount of time. Level 6 reflects
      modified independence and includes use of an assistive device or not completing
      the task in a timely or safe manner. OBJECTIVE: To examine the utility of the
      WeeFIM in Chinese children and to create a normative WeeFIM profile suitable for
      Chinese children. METHOD: Direct interviews were conducted for 445 normal Chinese
      children, aged 6 months to 7 years, in the community. RESULTS: 1. WeeFIM total
      score and 3 domains subscores versus age. The total WeeFIM scores increased
      progressively with age, reaching a plateau at 72 months. There was a progressive
      increase in subscores of self-care, mobility, and cognition independence between
      6 to 62 months, especially between 6 to 45 months. Similarly, the WeeFIM self
      care subscores increased progressively with age, reaching a plateau at around 72
      months. The WeeFIM mobility subscores increased progressively with age, reaching
      a plateau at around 54 months. The WeeFIM cognition subscores increased
      progressively with age, reaching a later plateau at around 80 months. 2. WeeFIM
      subtotal scores versus age. The total WeeFIM score and 3 domain subscores
      correlated significantly with age. We further classified the 18 items into 3
      groups according to the degree of correlation with age. Most items had high
      correlation with Spearman's correlation coefficient of rho >0.8. Only 1 item
      (chair transfer) showed moderate correlation with rho = 0.7-0.8. The item "walk"
      had the lowest correlation with rho = 0.6-0.7. 3. Chronological order for
      achieving different items. The 50th percentile of age in months for achieving
      level 6 (modified independence) of the 18 items were compared and ranked
      according to the age of achieving level 6. In creating a developmental scale of
      achievement of level 6 (modified independence) for all 18 items, the
      developmental sequence clustered in the following order: chair transfer (order 1)
      and walk (order 2) were achieved much earlier (at 18 and 24 months,
      respectively). Thereafter, there was a clustering of 4 items achieved at around
      45 months: toilet transfer (order 3), stair (order 4), expression (order 5), and
      social interaction (order 6). Then, 9 items were achieved at around 54 to 56
      months: tub or shower transfer (order 7), eating (order 8), bathing (order 9),
      bowel management (order 10), dressing of lower body (order 11), comprehension
      (order 12), dressing of upper body (order 13), bladder management (order 14), and
      grooming (order 15). At 60 months, the following ranked in order: memory (order
      16), problem-solving (order 17), and toileting (order 18). 4. Impact of sex
      factor. Girls aged 22 to 45 months had higher scores in self-care subscores and
      cognition subscores. From 63 months onwards, boys had statistically significant
      higher scores in mobility subscores. Otherwise, there was no statistically
      significant difference in WeeFIM scores for different age groups. 5. Impact of
      domestic helpers. There was also significant difference for self-care subscore
      with the presence of a maid at home. Those children with a maid at home obtained
      lower self-care subscores. However, the mobility and cognition subscores were not
      affected. CONCLUSION: We have created a normative functional independence profile
      for Chinese children by adapting the American-based WeeFIM. There were cultural
      differences when compared with American children. Interestingly, Chinese children
      in Hong Kong scored better than their American counterparts in domain 1 (self
      care) in all ages. This might be attributable to early attendance in preschool
      settings where children are taught to tend to their needs. Even for domain 2
      (mobility), the higher scores in younger Chinese children in Hong King (<3 years)
      might be explained by earlier attendance in preschool settings. The American
      children did catch up after 3 years. As for domain 3 (cognition), the local
      educational system emphasized reading, writing, memorizing materials, and social
      interaction. Thus, Chinese children in Hong Kong had better cognition scores
      until 42 months, when their American counterparts caught up by attending
      preschool. There are definitely environmental and cultural practices affecting
      functional independence in both ethnic groups, especially in the upper age range
      (>4 years) both in America and Hong Kong. Thus, a locally validated WeeFIM
      instrument should be adopted for Chinese children. Our study demonstrated that
      WeeFIM could be used as a functional independence measure for Chinese children.
      Hong Kong has a different cultural background compared with America; thus, usage
      of WeeFIM with different age criteria for achieving independence should be
      adopted.

PMID- 11826247
TI  - Successful antiangiogenic therapy of giant cell angioblastoma with interferon
      alfa 2b: report of 2 cases.
AB  - We describe 2 cases of angioblastoma, a rare, destructive pediatric tumor,
      treated with interferon alfa 2b (IFNalpha2b). The first patient is a 10-month-old
      male who presented with an ulcerated palatal neoplasm that could not be
      completely resected. The second is a male neonate with a congenital tumor of the
      right hand that invaded the hypothenar eminence, destroying the fourth and fifth
      metacarpals. Biopsy in both patients was interpreted as giant cell angioblastoma.
      Angioblastoma is rare; there is only 1 reported case that necessitated amputation
      of an upper extremity, also initially recommended for our patient. Because there
      is little experience with chemotherapy, permission was granted to employ an
      antiangiogenic regimen of IFNalpha2b. The angiogenic protein, basic fibroblast
      growth factor (bFGF), was abnormally elevated in both patients. Both patients
      received IFNalpha2b. In the first child, it was used after incomplete resection,
      because biopsy-proven tumor was present at the margin and in the nasopharynx.
      Biopsies 15 months after initiation of IFN2alphab were negative for tumor.
      Therapy was stopped after 3 years. Eighteen months later, the patient remains
      disease-free. In the second child, IFNalpha2b was started after debridement of
      the ulcerated tumor. Over 11 months, the tumor completely regressed and there was
      bony regeneration of the metacarpals. The fifth digit was amputated because of
      damage to the metacarpophalangeal joint by the tumor. IFNalpha2b therapy was
      discontinued after 1 year of treatment, and the child remains disease-free 2
      years and 8 months later. In conclusion, this report demonstrates that: 1) a bFGF
      overexpressing low-grade tumor can respond to IFNalpha2b in a manner similar to
      life-threatening infantile hemangiomas, 2) urinary bFGF levels can help guide
      IFNalpha dosage in such patients, and 3) although bFGF-mediated tumor
      angiogenesis is inhibited by IFNalpha, physiologic angiogenesis seems to be
      unaffected.

PMID- 11826248
TI  - Cochleovestibular impairment in pediatric Cogan's syndrome.
AB  - Cogan's syndrome is a rare, chronic inflammatory disorder that typically targets
      the eyes and vestibuloauditory apparatus, but it may also involve other organs.
      Three pediatric cases of Cogan's syndrome (ages 5, 13, and 18 years) are reported
      with long-term follow-up and complete and regular cochleovestibular functional
      evaluation and ophthalmologic and neurologic examinations. One case was a typical
      form (characterized by an interstitial keratitis and cochleovestibular
      impairment), whereas the other 2 cases were atypical forms with uveitis and
      polyarthritis. In all 3 cases, the first clinical sign was nonspecific eye
      redness misdiagnosed as a banal conjunctivitis, initially or secondarily
      associated with bilateral endocochlear sensorineural hearing loss and complete
      bilateral peripheral vestibular deficit. During the acute phase, early steroid
      treatment (prednisone, 1 mg/kg/day) was effective in treating the ocular lesions
      (3 of 3 cases) and improving hearing (2 of 3 cases) but less effective for the
      vestibular loss (2 of 3 cases). Adverse effects and dependence on the steroid
      occurred in 2 cases, and immunosuppressive drugs were necessary to avoid
      recurrences in 1 case. Over the long-term, the disease was controlled in 2 cases
      but continued to progress in the other. Cogan's syndrome in childhood should be
      suspected in cases of conjunctivitis associated with inner-ear symptoms; a prompt
      steroid treatment can avoid progressive impairment of multiple sensorineural
      functions (vision, balance, hearing). Long-term management involves limiting
      disease recurrences by adaptive therapies, screening for complications (aortitis
      in particular), and planning rehabilitation for the sensorial deficits.

PMID- 11826250
TI  - Defining asthma in the preschool-aged child.
AB  - A physician faces many challenges in making a definitive diagnosis of asthma in
      young children. Although there are clinical and historical features consistent
      with asthma, identical features are present in many other diseases. Furthermore,
      there is no specific test for asthma. Other diseases must always be ruled out
      before a definitive diagnosis of asthma is made. Determining whether cough or
      wheeze is the primary symptom is important because asthma is primarily a wheezing
      disease. Sweat chloride testing, chest radiography, and allergy skin testing
      should be performed in children with persistent wheezing to rule out other causes
      and help support a diagnosis of asthma. Allergy skin testing provides
      particularly useful information for making a diagnosis of asthma in the preschool
      aged child. A chart review of patients presenting consecutively to the Division
      of Allergy and Pulmonary Medicine provides insight and information on an approach
      to make an asthma diagnosis for this population.

PMID- 11826251
TI  - Development of wheezing disorders and asthma in preschool children.
AB  - Recent longitudinal studies have shed light on the pathogenesis and progression
      of asthma. The patterns of expression of childhood asthma that persist into adult
      life have been explored. Distinct asthma phenotypes (transient wheezing,
      nonatopic wheezing, and atopy-associated asthma) have been identified. Defining
      which children are at risk for persistent asthma could allow for better
      management and, potentially, for reduced morbidity and mortality.

PMID- 11826252
TI  - Inflammation in childhood asthma and other wheezing disorders.
AB  - It has become clear in the last few decades that the primary underlying pathology
      of asthma is airway tissue inflammation. In asthma, airway remodeling occurs
      during chronic inflammation, even in very young children. One of the key goals in
      treating asthma is to identify those young children with an asthmatic phenotype
      and initiate early treatment to avoid irreversible airway remodeling.
      Distinguishing asthma from other conditions that induce wheezing is a daunting
      but critical step in the appropriate treatment of asthma. In some children,
      hallmark mediators of inflammation, such as increased eosinophil levels, may
      distinguish asthma from other causes of wheezing, such as viral infections.
      Although progress has been made in the differential diagnoses of asthma in young
      children, more research is needed to define unique markers for distinguishing
      asthma from other respiratory conditions that produce wheezing.

PMID- 11826253
TI  - Inhaled corticosteroid therapy for asthma in preschool children: growth issues.
AB  - Although inhaled corticosteroids (ICS) have emerged as the preventive treatment
      of choice for persistent asthma, few studies have been conducted in infants and
      very young children that assess the benefits and risks of ICS therapy,
      particularly with regard to growth. Oral glucocorticoids inhibit growth at
      multiple levels by blunting pulsatile growth hormone (GH) secretion, decreasing
      insulin-like growth factor-1 bioactivity, and directly inhibiting new collagen
      synthesis. Normal childhood growth can be divided conceptually into 3 phases
      according to primary growth-supporting factors: nutrition-dependent growth of
      infancy, GH-dependent childhood growth, and sex steroid/GH stimulation of
      pubertal growth. Susceptibility to glucocorticoid-induced growth suppression
      appears to increase during periods of transition from one phase to another,
      particularly in the immediate prepubertal years. Studies using ICS at varying
      dosages demonstrate the possibility of short-term growth suppression, but long
      term studies suggest a negligible effect, if any, on final adult height or bone
      mineral density. Although certain speculations regarding the safety of ICS use in
      infants and very young children can be made based on these data, age-specific
      studies are needed to account for effects of differences in oral versus airway
      deposition and growth axis resiliency, which may occur in these patients.

PMID- 11826254
TI  - Balancing safety and efficacy in pediatric asthma management.
AB  - In the treatment of childhood asthma, balancing safety and efficacy is key to
      achieving optimal therapeutic benefit. Inhaled corticosteroids (ICS), because of
      their efficacy, remain a cornerstone in managing persistent pediatric asthma, but
      also are associated with significant adverse effects, including growth
      suppression. Consequently, careful attention must be given to balancing their
      safety and efficacy, which should include an understanding of airway patency and
      systemic absorption (dose, disease severity, propellant and lipophilicity of
      inhalant), bioavailability (inhalation technique, propellant, delivery devices,
      and hepatic first-pass metabolism), techniques for using minimum effective doses
      (dosing time, add-on therapy), and reduction of other exacerbating conditions
      (allergens, influenza, upper-respiratory diseases). The growth-suppressive
      effects of ICS may be most evident in children with: 1) mild asthma because the
      relatively high airway patency may facilitate increased levels of deposition and
      steroid absorption in more distal airways, and 2) evening dosing that may reduce
      nocturnal growth hormone activity. A step-down approach targeting a minimum
      effective dose and once-daily morning dosing is suggested for achieving the most
      acceptable safety/efficacy balance with ICS. The achievement of regular, safe,
      and correct ICS use requires significant knowledge and time for both caregiver
      and patient. Chromones, methylxanthines, long-acting beta-agonists, and
      leukotriene receptor antagonists are currently available alternatives to ICS for
      the control of persistent childhood asthma. Chromones are safe but, like
      methylxanthines, are difficult to use and frequently result in compromised
      effectiveness. Long-acting beta-agonists are not recommended as monotherapy for
      persistent asthma. Several factors that support leukotriene receptor antagonists
      as a therapeutic option for mild-to-moderate persistent pediatric asthma include
      established efficacy, good safety profiles, and simple, oral dosing. Physicians
      must evaluate and compare the balance of safety and efficacy for each agent to
      determine the appropriate asthma therapy for individual patients.

PMID- 11826255
TI  - Outcome measures in childhood asthma.
AB  - Although evidence suggests that asthma onset occurs early in childhood, many
      standard asthma outcome measures are either impractical or unreliable in
      preschool-aged children. In this population, for instance, patient history and
      symptom reports rely on the observations of caregivers, who tend to underreport
      their child's asthma symptoms. Furthermore, the use of conventional measures of
      pulmonary function such as spirometry may be impractical in very young children.
      Recent clinical studies have used a variety of techniques to measure symptoms,
      pulmonary function, and cellular mediators of inflammation. Outcomes such as
      discontinuation and exacerbation rates, frequency of daytime and nocturnal
      symptoms, and caregiver assessments of quality of life can be useful measures in
      evaluating outcomes in young children with asthma. Some measures, such as
      plethysmography and inflammatory marker analysis, may be suitable options for
      assessing pulmonary function and predicting asthma susceptibility in preschool
      aged children. Indeed, altered levels of inflammatory markers, including
      immunoglobulin E, interleukin-10, and exhaled nitric oxide, may be useful tools
      in diagnosing asthma, evaluating interventions, and assessing future risks for
      asthma symptomatology in very young children. Whether 1 or more of these outcome
      measures will prove useful clinically in improving the diagnosis and management
      of childhood asthma remains uncertain, although early research results are
      encouraging.

PMID- 11826256
TI  - Recurrent abdominal pain.

PMID- 11826257
TI  - Kidney failure in infants and children.

PMID- 11826258
TI  - Index of suspicion.

PMID- 11826259
TI  - ADHD, growth deficits, and relationships to psychostimulant use.

PMID- 11826260
TI  - Recognizing and diagnosing pancreatic insufficiency in infants.

PMID- 11826261
TI  - A hundred years of sodium pumping.
AB  - This article gives a history of the evidence (a) that animal cell membranes
      contain pumps that expel sodium ions in exchange for potassium ions; (b) that the
      pump derives energy from the hydrolysis of ATP; (c) that it is thermodynamically
      reversible-artificially steep transmembrane ion gradients make it run backward
      synthesizing ATP from ADP and orthophosphate; (d) that its mechanism is a ping
      pong one, in which phosphorylation of the pump by ATP is associated with an
      efflux of three sodium ions, and hydrolysis of the phosphoenzyme is associated
      with an influx of two potassium ions; (e) that each half of the working cycle
      involves both the transfer of a phosphate group and a conformational change-the
      phosphate transfer being associated with the occlusion of ions bound at one
      surface and the conformational change releasing the occluded ions at the opposite
      surface.

PMID- 11826262
TI  - Potassium channel ontogeny.
AB  - Potassium channels are multi-subunit complexes, often composed of several
      polytopic membrane proteins and cytosolic proteins. The formation of these
      oligomeric structures, including both biogenesis and trafficking, is the subject
      of this review. The emphasis is on events in the endoplasmic reticulum (ER),
      particularly on how, where, and when K(+) channel polypeptides translocate and
      integrate into the bilayer, oligomerize and fold to form pore-forming units, and
      associate with auxiliary subunits to create the mature channel complex. Questions
      are raised with respect to the sequence of these events, when biogenic decisions
      are made, models for integration of K(+) channel transmembrane segments,
      crosstalk between the cell surface and ER, and recognition of compatible partner
      subunits. Also considered are determinants of subunit composition and
      stoichiometry, their consequence for trafficking, mechanisms for ER retention and
      export, and sequence motifs that direct channels to the cell surface. It is these
      mechanistic issues that govern the differential distributions of K(+)
      conductances at the cell surface, and hence the electrical activity of cells and
      tissues underlying both the physiology and pathophysiology of an organism.

PMID- 11826263
TI  - Prolactin: the new biology of an old hormone.
AB  - Prolactin (PRL) is a paradoxical hormone. Historically known as the pituitary
      hormone of lactation, it has had attributed to it more than 300 separate actions,
      which can be correlated to the quasi-ubiquitous distribution of its receptor.
      Meanwhile, PRL-related knockout models have mainly highlighted its irreplaceable
      role in functions of lactation and reproduction, which suggests that most of its
      other reported target tissues are presumably modulated by, rather than strictly
      dependent on, PRL. The multiplicity of PRL actions in animals is in direct
      opposition to the paucity of arguments that suggest its involvement in human
      pathophysiology other than effects on reproduction. Although many experimental
      data argue for a role of PRL in the progression of some tumors, such as breast
      and prostate cancers, drugs lowering circulating PRL levels are ineffective. This
      observation opens new avenues for research into the understanding of whether
      local production of PRL is involved in tumor growth and, if so, how
      extrapituitary PRL synthesis is regulated. Finally, the physiological relevance
      of PRL variants, such as the antiangiogenic 16K-like PRL fragments, needs to be
      elucidated. This review is aimed at critically discussing how these recent
      findings have renewed the manner in which PRL should be considered as a
      multifunctional hormone.

PMID- 11826264
TI  - Ovulation: new dimensions and new regulators of the inflammatory-like response.
AB  - Ovulation is a complex process that is initiated by the lutenizing hormone surge
      and is controlled by the temporal and spatial expression of specific genes. This
      review focuses on recent endocrine, biochemical, and genetic information that has
      been derived largely from the identification of new genes that are expressed in
      the ovary, and from knowledge gained by the targeted deletion of genes that
      appear to impact the ovulation process. Two main areas are described in most
      detail. First, because mutant mouse models indicate that appropriate formation of
      the cumulus matrix is essential for successful ovulation, genes expressed in the
      cumulus cells and those that control cumulus expansion are discussed. Second,
      because mice null for the progesterone receptor fail to ovulate and are ideal
      models for dissecting the critical events downstream of progesterone receptor,
      genes expressed in mural granulosa cells that regulate the expression of novel
      proteases are described.

PMID- 11826265
TI  - Aromatase--a brief overview.
AB  - There is growing awareness that androgens and estrogens have general metabolic
      roles that are not directly involved in reproductive processes. These include
      actions on vascular function, lipid and carbohydrate metabolism, as well as bone
      mineralization and epiphyseal closure in both sexes. In postmenopausal women, as
      in men, estrogen is no longer solely an endocrine factor but instead is produced
      in a number of extragonadal sites and acts locally at these sites in a paracrine
      and intracrine fashion. These sites include breast, bone, vasculature, and brain.
      Within these sites, aromatase action can generate high levels of estradiol
      locally without significantly affecting circulating levels. Circulating C19
      steroid precursors are essential substrates for extragonadal estrogen synthesis.
      The levels of these androgenic precursors decline markedly with advancing age in
      women, possible from the mid-to-late reproductive years. This may be a
      fundamental reason why women are at increased risk for bone mineral loss and
      fracture, and possibly decline of cognitive function, compared with men.
      Aromatase expression in these various sites is under the control of tissue
      specific promotors regulated by different cohorts of transcription factors. Thus
      in principle, it should be possible to develop selective aromatase modulators
      (SAMs) that block aromatase expression, for example, in breast, but allow
      unimpaired estrogen synthesis in other tissues such as bone.

PMID- 11826266
TI  - G proteins and pheromone signaling.
AB  - All cells have the capacity to respond to chemical and sensory stimuli. Central
      to many such signaling pathways is the heterotrimeric G protein, which transmits
      a signal from cell surface receptors to intracellular effectors. Recent studies
      using the yeast Saccharomyces cerevisiae have produced important advances in our
      understanding of G protein activation and inactivation. This review focuses on
      the mechanisms by which G proteins transmit a signal from peptide pheromone
      receptors to the mating response in yeast and how mechanisms elucidated in yeast
      can provide insights to signaling events in more complex organisms.

PMID- 11826267
TI  - G proteins and phototransduction.
AB  - Phototransduction is the process by which a photon of light captured by a
      molecule of visual pigment generates an electrical response in a photoreceptor
      cell. Vertebrate rod phototransduction is one of the best-studied G protein
      signaling pathways. In this pathway the photoreceptor-specific G protein,
      transducin, mediates between the visual pigment, rhodopsin, and the effector
      enzyme, cGMP phosphodiesterase. This review focuses on two quantitative features
      of G protein signaling in phototransduction: signal amplification and response
      timing. We examine how the interplay between the mechanisms that contribute to
      amplification and those that govern termination of G protein activity determine
      the speed and the sensitivity of the cellular response to light.

PMID- 11826268
TI  - G proteins and olfactory signal transduction.
AB  - The olfactory system sits at the interface of the environment and the nervous
      system and is responsible for correctly coding sensory information from thousands
      of odorous stimuli. Many theories existed regarding the signal transduction
      mechanism that mediates this difficult task. The discovery that odorant
      transduction utilizes a unique variation (a novel family of G protein-coupled
      receptors) based upon a very common theme (the G protein-coupled adenylyl cyclase
      cascade) to accomplish its vital task emphasized the power and versatility of
      this motif. We now must understand the downstream consequences of this cascade
      that regulates multiple second messengers and perhaps even gene transcription in
      response to the initial interaction of ligand with G protein-coupled receptor.

PMID- 11826269
TI  - Mycosporine-like amino acids and related Gadusols: biosynthesis, acumulation, and
      UV-protective functions in aquatic organisms.
AB  - Organisms living in clear, shallow water are exposed to the damaging wavelengths
      of solar ultraviolet radiation (UVR) coincident with the longer wavelengths of
      photosynthetically available radiation (PAR) also necessary for vision. With the
      general exception of bacteria, taxonomically diverse marine and freshwater
      organisms have evolved the capacity to synthesize or accumulate UV-absorbing
      mycosporine-like amino acids (MAAs), presumably for protection against
      environmental UVR. This review highlights the evidence for this UV-protective
      role while also considering other attributed functions, including reproductive
      and osmotic regulation and vision. Probing the regulation and biosynthesis of
      MAAs provides insight to the physiological evolution and utility of UV protection
      and of biochemically associated antioxidant defenses.

PMID- 11826270
TI  - Hypoxia-induced anapyrexia: implications and putative mediators.
AB  - Hypoxia elicits an array of compensatory responses in animals ranging from
      protozoa to mammals. Central among these responses is anapyrexia, the regulated
      decrease of body temperature. The importance of anapyrexia lies in the fact that
      it reduces oxygen consumption, increases the affinity of hemoglobin for oxygen,
      and blunts the energetically costly responses to hypoxia. The mechanisms of
      anapyrexia are of intense interest to physiologists. Several substances, among
      them lactate, adenosine, opioids, and nitric oxide, have been suggested as
      putative mediators of anapyrexia, and most appear to act in the central nervous
      system. Moreover, there is evidence that the drop in body temperature in response
      to hypoxia, unlike the ventilatory response to hypoxia, does not depend on the
      activation of peripheral chemoreceptors. The current knowledge of the mechanisms
      of hypoxia-induced anapyrexia are reviewed.

PMID- 11826271
TI  - Calmodulin as an ion channel subunit.
AB  - A surprising variety of ion channels found in a wide range of species from Homo
      to Paramecium use calmodulin (CaM) as their constitutive or dissociable Ca(2+)
      sensing subunits. The list includes voltage-gated Ca(2+) channels, various Ca(2+)
      or ligand-gated channels, Trp family channels, and even the Ca(2+)-induced
      Ca(2+) release channels from organelles. Our understanding of CaM chemistry and
      its relation to enzymes has been instructive in channel research, yet the intense
      study of CaM regulation of ion channels has also revealed unexpected CaM
      chemistry. The findings on CaM channel interactions have indicated the existence
      of secondary interaction sites in addition to the primary CaM-binding peptides
      and the functional differences between the N- and C-lobes of CaM. The study of
      CaM in channel biology will figure into our understanding on how this uniform,
      universal, vital, and ubiquitous Ca(2+) decoder coordinates the myriad local and
      global cell physiological transients.

PMID- 11826272
TI  - Structure and function of dendritic spines.
AB  - Spines are neuronal protrusions, each of which receives input typically from one
      excitatory synapse. They contain neurotransmitter receptors, organelles, and
      signaling systems essential for synaptic function and plasticity. Numerous brain
      disorders are associated with abnormal dendritic spines. Spine formation,
      plasticity, and maintenance depend on synaptic activity and can be modulated by
      sensory experience. Studies of compartmentalization have shown that spines serve
      primarily as biochemical, rather than electrical, compartments. In particular,
      recent work has highlighted that spines are highly specialized compartments for
      rapid large-amplitude Ca(2+) signals underlying the induction of synaptic
      plasticity.

PMID- 11826273
TI  - Short-term synaptic plasticity.
AB  - Synaptic transmission is a dynamic process. Postsynaptic responses wax and wane
      as presynaptic activity evolves. This prominent characteristic of chemical
      synaptic transmission is a crucial determinant of the response properties of
      synapses and, in turn, of the stimulus properties selected by neural networks and
      of the patterns of activity generated by those networks. This review focuses on
      synaptic changes that result from prior activity in the synapse under study, and
      is restricted to short-term effects that last for at most a few minutes. Forms of
      synaptic enhancement, such as facilitation, augmentation, and post-tetanic
      potentiation, are usually attributed to effects of a residual elevation in
      presynaptic [Ca(2+)]i, acting on one or more molecular targets that appear to be
      distinct from the secretory trigger responsible for fast exocytosis and phasic
      release of transmitter to single action potentials. We discuss the evidence for
      this hypothesis, and the origins of the different kinetic phases of synaptic
      enhancement, as well as the interpretation of statistical changes in transmitter
      release and roles played by other factors such as alterations in presynaptic
      Ca(2+) influx or postsynaptic levels of [Ca(2+)]i. Synaptic depression dominates
      enhancement at many synapses. Depression is usually attributed to depletion of
      some pool of readily releasable vesicles, and various forms of the depletion
      model are discussed. Depression can also arise from feedback activation of
      presynaptic receptors and from postsynaptic processes such as receptor
      desensitization. In addition, glial-neuronal interactions can contribute to short
      term synaptic plasticity. Finally, we summarize the recent literature on putative
      molecular players in synaptic plasticity and the effects of genetic manipulations
      and other modulatory influences.

PMID- 11826274
TI  - Intracellular transport mechanisms of signal transducers.
AB  - Recent discoveries have revolutionized our conceptions of enzyme-substrate
      specificity in signal transduction pathways. Protein kinases A and C are
      localized to discreet subcellular regions, and this localization changes in an
      isozyme-specific manner upon activation, a process referred to as translocation.
      The mechanisms for translocation involve interactions of soluble kinases with
      membrane-bound anchor proteins that recognize individual kinase isoenzymes and
      their state of activation. Recently, modulation of kinase-anchor protein
      interactions has been used to specifically regulate, positively or negatively,
      the activity of C kinase isozymes. Also described in this review is a role for
      the Rab family of small G proteins in regulating subcellular protein trafficking.
      The pathophysiological significance of disrupted subcellular protein transport in
      cell signaling and the potential therapeutic utility of targeted regulation of
      these events are in the process of being characterized.

PMID- 11826275
TI  - Cardiac ion channels.
AB  - The normal electrophysiologic behavior of the heart is determined by ordered
      propagation of excitatory stimuli that result in rapid depolarization and slow
      repolarization, thereby generating action potentials in individual myocytes.
      Abnormalities of impulse generation, propagation, or the duration and
      configuration of individual cardiac action potentials form the basis of disorders
      of cardiac rhythm, a continuing major public health problem for which available
      drugs are incompletetly effective and often dangerous. The integrated activity of
      specific ionic currents generates action potentials, and the genes whose
      expression results in the molecular components underlying individual ion currents
      in heart have been cloned. This review discusses these new tools and how their
      application to the problem of arrhythmias is generating new mechanistic insights
      to identify patients at risk for this condition and developing improved
      antiarrhythmic therapies.

PMID- 11826276
TI  - Fatty acid oxidation disorders.
AB  - Genetic disorders of mitochondrial fatty acid beta-oxidation have been recognized
      within the last 20 years as important causes of morbidity and mortality,
      highlighting the physiological significance of fatty acids as an energy source.
      Although the mammalian mitochondrial fatty acid-oxidizing system was recognized
      at the beginning of the last century, our understanding of its exact nature
      remains incomplete, and new components are being identified frequently.
      Originally described as a four-step enzymatic process located exclusively in the
      mitochondrial matrix, we now recognize that long-chain-specific enzymes are bound
      to the inner mitochondrial membrane, and some enzymes are expressed in a tissue
      specific manner. Much of our new knowledge of fatty acid metabolism has come from
      the study of patients who were diagnosed with single-gene autosomal recessive
      defects, a situation that seems to be further evolving with the emergence of
      phenotypes determined by combinations of multiple genetic and environmental
      factors. This review addresses the normal process of mitochondrial fatty acid
      beta-oxidation and discusses the clinical, metabolic, and molecular aspects of
      more than 20 known inherited diseases of this pathway that have been described to
      date.

PMID- 11826277
TI  - Molecular chaperones in the kidney.
AB  - The normal milieu of the kidney includes hypoxia, large osmotic fluxes, and an
      enormous amount of fluid/solute reabsorption. Renal adaptation to these
      conditions requires a host of molecular chaperones that stabilize protein
      conformation, target nascent proteins to their final intracellular destination,
      and prevent protein aggregation. Under physiologic or pharmacologic stress,
      inducible molecular chaperones provide additional mechanisms for repairing or
      degrading non-native proteins and for inhibiting stress-induced apoptosis. In
      contrast to intracellular chaperones, chaperones present on the cell surface
      regulate the immune system and have cytokine-like effects. A diverse range of
      chaperones and chaperone functions provide the renal cell with an armamentarium
      of responses to improve the chances of survival.

PMID- 11826279
TI  - The renin angiotensin system and kidney development.
AB  - When angiotensin II or AT1 receptor is experimentally inhibited during the
      perinatal period, either by pharmacological intervention or genetic manipulation,
      the kidney develops with profound structural abnormalities. Most prominent are
      hypertrophy of arterial vasculatures and atrophy of the papilla. Although the
      mechanism by which the vascular hypertrophy occurs remains unknown, study of the
      atrophic papilla gives us a new clue for understanding the physiological role of
      angiotensin. Mutant mice completely devoid of AT1 receptor fail to develop the
      renal pelvis and the ureteral peristaltic movement. Normally, angiotensin and AT1
      receptor are transiently up-regulated around the renal outlet at birth. Thus
      angiotensin II induces the peristaltic machinery during the perinatal period in a
      timely fashion to accommodate the dramatic increase in urine production that
      occurs during the transition from intra- to extra-uterine life. Further studies
      revealed that in adult animals angiotensin augments the peristaltic movement when
      the urinary tract is partially obstructed, thereby protecting the kidney from
      hydronephrosis. This newly discovered function of angiotensin to protect kidney
      architecture at the time of urine outflow obstruction is reminiscent of its
      similar kidney structure-protecting function that is active during arterial blood
      flow obstruction.

PMID- 11826278
TI  - Molecular mechanism of active Ca2+ reabsorption in the distal nephron.
AB  - The identification of the epithelial Ca(2+) channel (ECaC) complements the group
      of Ca(2+) transport proteins including calbindin-D28K, Na(+)/Ca(2+) exchanger and
      plasma membrane Ca(2+)-ATPase, which are co-expressed in 1,25(OH)2D3- responsive
      nephron segments. ECaC constitutes the rate-limiting apical entry step in the
      process of active transcellular Ca(2+) transport and belongs to a superfamily of
      Ca(2+) channels that includes the vanilloid receptor and transient receptor
      potential channels. This new Ca(2+) channel consists of six transmembrane
      spanning domains, including a pore-forming hydrophobic stretch between domain 5
      and 6. The C- and N-terminal tails contain several conserved regulatory sites,
      implying that the channel function is modulated by regulatory proteins. The
      distinctive functional properties of ECaC include a constitutively activated
      Ca(2+) permeability, a high selectivity for Ca(2+), hyperpolarization-stimulated
      and Ca(2+)-dependent feedback regulation of channel activity, and 1,25(OH)2D3
      induced gene activation. This review covers the distinctive properties of this
      new highly Ca(2+)-selective channel and highlights the implications for active
      transcellular Ca(2+) reabsorption in health and disease.

PMID- 11826280
TI  - Molecular aspects of renal anionic drug transport.
AB  - Multiple organic anion transporters in the proximal tubule of the kidney are
      involved in the secretion of drugs, toxic compounds, and their metabolites. Many
      of these compounds are potentially hazardous on accumulation, and it is therefore
      not surprising that the proximal tubule is also an important target for toxicity.
      In the past few years, considerable progress has been made in the cloning of
      these transporters and their functional characterization following heterologous
      expression. Members of the organic anion transporter (OAT), organic anion
      transporting polypeptide (OATP), multidrug resistance protein (MRP), sodium
      phosphate transporter (NPT), and peptide transporter (PEPT) families have been
      identified in the kidney. In this review, we summarize our current knowledge on
      their localization, molecular and functional characteristics, and substrate and
      inhibitor specificity. A major challenge for the future will be to understand how
      these transporters work in concert to accomplish the renal secretion of specific
      anionic substrates.

PMID- 11826281
TI  - Trafficking of canalicular ABC transporters in hepatocytes.
AB  - ATP-binding cassette (ABC) transporters located in the hepatocyte canalicular
      membrane of mammalian liver are critical players in bile formation and
      detoxification. Although ABC transporters have been well characterized
      functionally, only recently have several canalicular ABC transporters been cloned
      and their molecular nature revealed. Subsequently, development of specific
      antibodies has permitted a detailed investigation of ABC transporter intrahepatic
      distribution under varying physiological conditions. It is now apparent that
      there is a complex array of ABC transporters in hepatocytes. ABC transporter
      molecules reside in intrahepatic compartments and are delivered to the
      canalicular domain following increased physiological demand to secrete bile.
      Insufficient amounts of ABC transporters in the bile canalicular membrane result
      in cholestasis (i.e., bile secretory failure). Therefore, elucidation of the
      intrahepatic pathways and regulation of ABC transporters may help to understand
      the cause of cholestasis at a molecular level and provide clues for novel
      therapies.

PMID- 11826282
TI  - Chloride channels and hepatocellular function: prospects for molecular
      identification.
AB  - Hepatocytes possess chloride channels at the plasma membrane and in multiple
      intracellular compartments. These channels are required for cell volume
      regulation and acidification of intracellular organelles. Evidence also supports
      a role of chloride channels in modulation of apoptosis and cell growth. Swelling-
      and Ca(2+)-activated chloride channels have been identified in hepatocyte plasma
      membranes, and chloride channels have been observed in the membranes of
      lysosomes, endosomes, Golgi, endoplasmic reticulum, mitochondria, and the
      nucleus. This review summarizes the functions of these channels and discusses the
      specific channel molecules they may represent. Chloride channel molecules shown
      to be expressed in hepatocytes include members of the ClC channel family (ClC-2,
      ClC-3, ClC-5, and ClC-7), members of the newly identified CLIC family of
      intracellular chloride channels (CLIC-1 and CLIC-4), the mitochondrial voltage
      dependent anion channel, and a newly identified intracellular channel, MCLC (Mid
      1 related chloride channel). Current understanding does not include a molecular
      identification of most of the observed channel functions, but details of the
      molecular properties of these channel molecules should allow future
      identification and further understanding of chloride channel function in
      hepatocytes.

PMID- 11826283
TI  - Bile salt transporters.
AB  - Bile salts are the major organic solutes in bile and undergo extensive
      enterohepatic circulation. Hepatocellular bile salt uptake is mediated
      predominantly by the Na(+)-taurocholate cotransport proteins Ntcp (rodents) and
      NTCP (humans) and by the Na(+)-independent organic anion-transporting
      polypeptides Oatp1, Oatp2, and Oatp4 (rodents) and OATP-C (humans). After
      diffusion (bound by intracellular bile salt-binding proteins) to the canalicular
      membrane, monoanionic bile salts are secreted into bile canaliculi by the bile
      salt export pump Bsep (rodents) or BSEP (humans). Both belong to the ATP-binding
      cassette (ABC) transporter superfamily. Dianionic conjugated bile salts are
      secreted into bile by the multidrug-resistance-associated proteins Mrp2/MRP2. In
      bile ductules, a minor portion of protonated bile acids and monomeric bile salts
      are reabsorbed by non-ionic diffusion and the apical sodium-dependent bile salt
      transporter Asbt/ASBT, transported back into the periductular capillary plexus by
      Mrp3/MRP3 [and/or a truncated form of Asbt (tAsbt)], and subjected to
      cholehepatic shunting. The major portion of biliary bile salts is aggregated into
      mixed micelles and transported into the intestine, where they are reabsorbed by
      apical Oatp3, the apical sodium-dependent bile salt transporter (ASBT), cytosolic
      intestinal bile acid-binding protein (IBABP), and basolateral Mrp3/MRP3 and
      tAsbt. Transcriptional and posttranscriptional regulation of these enterohepatic
      bile salt transporters is closely related to the regulation of lipid and
      cholesterol homeostasis. Furthermore, defective expression and function of bile
      salt transporters have been recognized as important causes for various
      cholestatic liver diseases.

PMID- 11826284
TI  - Mechanisms of iron accumulation in hereditary hemochromatosis.
AB  - Hereditary hemochromatosis (HH) is a common inborn error of iron metabolism
      characterized by excess dietary iron absorption and iron deposition in several
      tissues. Clinical consequences include hepatic failure, hepatocellular carcinoma,
      diabetes, cardiac failure, impotence, and arthritis. Despite the discovery of the
      mutation underlying most cases of HH, considerable uncertainty exists in the
      mechanism by which the normal gene product, HFE, regulates iron homeostasis.
      Knockout of the HFE gene clearly confers the HH phenotype on mice. However,
      studies on HFE expressed in cultured cells have not yet clarified the mechanism
      by which HFE mutations lead to increased dietary iron absorption. Recent
      discoveries suggest other genes, including a second transferrin receptor and the
      circulating peptide hepcidin, participate in a shared pathway with HFE in
      regulation of iron absorption. This review summarizes our current understanding
      of the relationship between iron stores and absorption and presents models to
      explain the dysregulated iron homeostasis in HH.

PMID- 11826285
TI  - Molecular pathogenesis of lung cancer.
AB  - Lung cancer is the most common cause of cancer death in the United States,
      killing more than 156,000 people every year. In the past two decades, significant
      progress has been made in understanding the molecular and cellular pathogenesis
      of lung cancer. Abnormalities of proto-oncogenes, genetic and epigenetic changes
      of tumor suppressor genes, the role of angiogenesis in the multistage development
      of lung cancer, as well as detection of molecular abnormalities in preinvasive
      respiratory lesions, have recently come into focus. Efforts are ongoing to
      translate these findings into new clinical strategies for risk assessment,
      chemoprevention, early diagnosis, treatment selection, and prognosis and to
      provide new targets and methods of treatment for lung cancer patients. All these
      strategies should aid in reducing the number of newly diagnosed lung cancer cases
      and in increasing the survival and quality of life of patients with lung cancer.

PMID- 11826286
TI  - [beta]-defensins in lung host defense.
AB  - Host defenses at the mucosal surface of the airways evolved to present many
      layers of protection against inhaled microbes. Normally, the intrapulmonary
      airways are sterile. Airway secretions contain numerous factors with
      antimicrobial activity that contribute to innate defenses. Many protein and
      peptide components exert bacteriostatic or bacteriocidal effects against a wide
      variety of organisms and may act in synergistic or additive combinations. The
      beta-defensins are a relatively recently described family of peptide
      antimicrobials that are widely expressed at mucosal surfaces, including airway
      and submucosal gland epithelia. These small cationic peptides are products of
      individual genes that exhibit broad-spectrum activity against bacteria, fungi,
      and some enveloped viruses. Their expression in airway epithelia may be
      constitutive or inducible by bacterial products or pro-inflammatory cytokines.
      beta-defensins also act as chemokines for adaptive immune cells, including
      immature dendritic cells and T cells via the CCR6 receptor, and provide a link
      between innate and adaptive immunity. Alterations in the function of the beta
      defensins may contribute to disease states. Here we review much of the biology of
      the beta-defensins, including gene discovery, genomic organization, molecular
      structure, regulation of expression, and function.

PMID- 11826287
TI  - Regulation of endothelial nitric oxide synthase: location, location, location.
AB  - Endothelial nitric oxide synthase (eNOS) is expressed in vascular endothelium,
      airway epithelium, and certain other cell types where it generates the key
      signaling molecule nitric oxide (NO). Diminished NO availability contributes to
      systemic and pulmonary hypertension, atherosclerosis, and airway dysfunction.
      Complex mechanisms underly the cell specificity of eNOS expression, and co- and
      post-translational processing leads to trafficking of the enzyme to plasma
      membrane caveolae. Within caveolae, eNOS is the downstream target member of a
      signaling complex in which it is functionally linked to both typical G protein
      coupled receptors and less typical receptors such as estrogen receptor (ER) alpha
      and the high-density lipoprotein receptor SR-BI displaying novel actions. This
      compartmentalization facilitates dynamic protein-protein interactions and calcium
      and phosphorylation-dependent signal transduction events that modify eNOS
      activity. Further understanding of these mechanisms will enable us to take
      preventive and therapeutic advantage of the powerful actions of NO in multiple
      cell types.

PMID- 11826288
TI  - Gm-CSF regulates pulmonary surfactant homeostasis and alveolar macrophage
      mediated innate host defense.
AB  - Recent studies in transgenic mice have revealed important insights into the roles
      of GM-CSF in regulation of surfactant homeostasis and lung host defense.
      Interruption of the GM-CSF signaling pathway by targeted ablation of the GM-CSF
      gene or its receptor (GM(-/-) or GM Rbetac(-/-) mice, respectively) resulted in
      pulmonary alveolar proteinosis (PAP) but no hematologic abnormalities. Alveolar
      macrophages from GM(-/-) mice have reduced capacity for surfactant catabolism,
      cell adhesion, phagocytosis, bacterial killing, Toll-receptor signaling, and
      expression of various pathogen-associated molecular pattern recognition
      receptors, suggesting arrest at an early stage of differentiation. PAP and
      abnormalities of alveolar macrophage function were corrected by local expression
      of GM-CSF in the lung, and expression of the transcription factor PU.1 in
      alveolar macrophages of GM(-/-) mice rescued most defects. Recently, a strong
      association of auto-antibodies to GM-CSF or GM-CSF receptor gene mutations with
      PAP has implicated GM-CSF signaling abnormalities in the pathogenesis of PAP in
      humans. Together, these observations demonstrate that GM-CSF has a critical role
      in regulation of surfactant homeostasis and alveolar macrophage innate immune
      functions in the lung.

PMID- 11826289
TI  - Human and murine phenotypes associated with defects in cation-chloride
      cotransport.
AB  - The diuretic-sensitive cotransport of cations with chloride is mediated by the
      cation-chloride cotransporters, a large gene family encompassing a total of seven
      Na-Cl, Na-K-2Cl, and K-Cl cotransporters, in addition to two related transporters
      of unknown function. The cation-chloride cotransporters perform a wide variety of
      physiological roles and differ dramatically in patterns of tissue expression and
      cellular localization. The renal-specific Na-Cl cotransporter (NCC) and Na-K-2Cl
      cotransporter (NKCC2) are involved in Gitelman and Bartter syndrome,
      respectively, autosomal recessive forms of metabolic alkalosis. The associated
      phenotypes due to loss-of-function mutations in NCC and NKCC2 are consistent, in
      part, with their functional roles in the distal convoluted tubule and thick
      ascending limb, respectively. Other cation-chloride cotransporters are positional
      candidates for Mendelian human disorders, and the K-Cl cotransporter KCC3, in
      particular, may be involved in degenerative peripheral neuropathies linked to
      chromosome 15q14. The characterization of mice with both spontaneous and targeted
      mutations of several cation-chloride cotransporters has also yielded significant
      insight into the physiological and pathophysiological roles of several members of
      the gene family. These studies implicate the Na-K-2Cl cotransporter NKCC1 in
      hearing, salivation, pain perception, spermatogenesis, and the control of
      extracellular fluid volume. Targeted deletion of the neuronal-specific K-Cl
      cotransporter KCC2 generates mice with a profound seizure disorder and confirms
      the central role of this transporter in modulating neuronal excitability.
      Finally, the comparison of human and murine phenotypes associated with loss-of
      function mutations in cation-chloride cotransporters indicates important
      differences in physiology of the two species and provides an important
      opportunity for detailed physiological and morphological analysis of the tissues
      involved.

PMID- 11826290
TI  - Renal genetic disorders related to K+ and Mg2+.
AB  - The recent knowledge of the renal epithelial transport systems has exploded with
      the identification, cloning, and characterization of a large number of membrane
      transport proteins. The fundamental aspects of these transporters are beginning
      to emerge at the molecular level and are summarized in the accompanying
      contributions in this volume of the Annual Review of Physiology. The aim of my
      review is to integrate this body of knowledge with the understanding of the
      clinical disorders of human mineral homeostasis that accompany gain, loss, or
      dysregulation of function of these transport systems. The specific focus is on
      the best defined human clinical syndromes in which there are derangements in K(+)
      and Mg(2+) homeostasis.

PMID- 11826291
TI  - Epithelial sodium channel and the control of sodium balance: interaction between
      genetic and environmental factors.
AB  - The epithelial sodium channel (ENaC) expressed in aldosterone-responsive
      epithelial cells of the kidney and colon plays a critical role in the control of
      sodium balance, blood volume, and blood pressure. In lung, ENaC has a distinct
      role in controlling the ionic composition of the air-liquid interface and thus
      the rate of mucociliary transport. Loss-of-function mutations in ENaC cause a
      severe salt-wasting syndrome in human pseudohypoaldosteronism type 1 (PHA-1).
      Gain-of-function mutations in ENaC beta and gamma subunits cause
      pseudoaldosteronism (Liddle's syndrome), a severe form of salt-sensitive
      hypertension. This review discusses genetically defined forms of a salt
      sensitivity and salt resistance in human monogenic diseases and in animal models
      mimicking PHA-1 or Liddle's syndrome. The complex interaction between genetic
      factors (ENaC mutations) and the risk factor (salt intake) can now be studied
      experimentally. The role of single-nucleotide polymorphisms (SNPs) in determining
      salt sensitivity or salt resistance in general populations is one of the main
      challenges of the post-genomic era.

PMID- 11826292
TI  - Genetic diseases of acid-base transporters.
AB  - Genetic disorders of acid-base transporters involve plasmalemmal and organellar
      transporters of H(+), HCO3(-), and Cl(-). Autosomal-dominant and -recessive forms
      of distal renal tubular acidosis (dRTA) are caused by mutations in ion
      transporters of the acid-secreting Type A intercalated cell of the renal
      collecting duct. These include the AE1 Cl(-)/HCO3(-) exchanger of the basolateral
      membrane and at least two subunits of the apical membrane vacuolar (v)H(+)
      ATPase, the V1 subunit B1 (associated with deafness) and the V0 subunit a4.
      Recessive proximal RTA with ocular disease arises from mutations in the
      electrogenic Na(+)-bicarbonate cotransporter NBC1 of the proximal tubular cell
      basolateral membrane. Recessive mixed proximal-distal RTA accompanied by
      osteopetrosis and mental retardation is associated with mutations in cytoplasmic
      carbonic anhydrase II. The metabolic alkalosis of congenital chloride-losing
      diarrhea is caused by mutations in the DRA Cl(-)/HCO3(-) exchanger of the
      ileocolonic apical membrane. Recessive osteopetrosis is caused by deficient
      osteoclast acid secretion across the ruffled border lacunar membrane, the result
      of mutations in the vH(+)-ATPase V0 subunit or in the CLC-7 Cl(-) channel. X
      linked nephrolithiasis and engineered deficiencies in some other CLC Cl(-)
      channels are thought to represent defects of organellar acidification. Study of
      acid-base transport disease-associated mutations should enhance our understanding
      of protein structure-function relationships and their impact on the physiology of
      cell, tissue, and organism.

PMID- 11826293
TI  - Foolish seedlings and DELLA regulators: the functions of rice SLR1 and
      Arabidopsis RGL1 in GA signal transduction.

PMID- 11826294
TI  - Plasmodesma 2001: on safari through the symplast.

PMID- 11826295
TI  - "Cross-talk" between cell division cycle and development in plants.

PMID- 11826296
TI  - Cytokinin growth responses in Arabidopsis involve the 26S proteasome subunit
      RPN12.
AB  - The 26S proteasome is an ATP-dependent eukaryotic protease responsible for
      degrading many important cell regulators, especially those conjugated with
      multiple ubiquitins. Bound on both ends of the 20S core protease is a
      multisubunit regulatory particle that plays a crucial role in substrate selection
      by an as yet unknown mechanism(s). Here, we show that the RPN12 subunit of the
      Arabidopsis regulatory particle is involved in cytokinin responses. A T-DNA
      insertion mutant that affects RPN12a has a decreased rate of leaf formation,
      reduced root elongation, delayed skotomorphogenesis, and altered growth responses
      to exogenous cytokinins, suggesting that the mutant has decreased sensitivity to
      the hormone. The cytokinin-inducible genes CYCD3 and NIA1 are upregulated
      constitutively in rpn12a-1, indicating that feedback-inhibitory mechanisms also
      may be altered. rpn12a-1 seedlings also showed changes in auxin-induced growth
      responses, further illustrating the close interaction between auxin and cytokinin
      regulation. In yeast, RPN12 is necessary for the G1/S and G2/M transitions of the
      cell cycle, phases that have been shown to be under cytokinin control in plants.
      We propose that RPN12a is part of the Arabidopsis 26S proteasome that controls
      the stability of one or more of the factors involved in cytokinin regulation.

PMID- 11826297
TI  - SGR2, a phospholipase-like protein, and ZIG/SGR4, a SNARE, are involved in the
      shoot gravitropism of Arabidopsis.
AB  - In higher plants, the shoot and the root generally show negative and positive
      gravitropism, respectively. To elucidate the molecular mechanisms involved in
      gravitropism, we have isolated many shoot gravitropism mutants in Arabidopsis.
      The sgr2 and zig/sgr4 mutants exhibited abnormal gravitropism in both
      inflorescence stems and hypocotyls. These genes probably are involved in the
      early step(s) of the gravitropic response. The sgr2 mutants also had misshapen
      seed and seedlings, whereas the stem of the zig/sgr4 mutants elongated in a
      zigzag fashion. The SGR2 gene encodes a novel protein that may be part of a gene
      family represented by bovine phosphatidic acid-preferring phospholipase A1
      containing a putative transmembrane domain. This gene family has been reported
      only in eukaryotes. The ZIG gene was found to encode AtVTI11, a protein that is
      homologous with yeast VTI1 and is involved in vesicle transport. Our observations
      suggest that the two genes may be involved in a vacuolar membrane system that
      affects shoot gravitropism.

PMID- 11826298
TI  - Involvement of the vacuoles of the endodermis in the early process of shoot
      gravitropism in Arabidopsis.
AB  - The endodermal cells of the shoot are thought to be the gravity-sensing cells in
      Arabidopsis. The amyloplasts in the endodermis that sediment in the direction of
      gravity may act as statoliths. Endodermis-specific expression of SGR2 and ZIG
      using the SCR promoter could complement the abnormal shoot gravitropism of the
      sgr2 and zig mutants, respectively. The abnormalities in amyloplast sedimentation
      observed in both mutants recovered simultaneously. These results indicate that
      both genes in the endodermal cell layer are crucial for shoot gravitropism. ZIG
      encodes AtVTI11, which is a SNARE involved in vesicle transport to the vacuole.
      The fusion protein of SGR2 and green fluorescent protein localized to the vacuole
      and small organelles. These observations indicate that ZIG and SGR2 are involved
      in the formation and function of the vacuole, a notion supported by the results
      of subcellular analysis of the sgr2 and zig mutants with electron microscopy.
      These results strongly suggest that the vacuole participates in the early events
      of gravitropism and that SGR2 and ZIG functions are involved.

PMID- 11826299
TI  - The gibberellin signaling pathway is regulated by the appearance and
      disappearance of SLENDER RICE1 in nuclei.
AB  - The slender rice1 mutant (slr1) shows a constitutive gibberellin (GA) response
      phenotype. To investigate the mode of action of SLR1, we generated transgenic
      rice expressing a fusion protein consisting of SLR1 and green fluorescent protein
      (SLR1-GFP) and analyzed the phenotype of the transformants and the subcellular
      localization of GFP in vivo. SLR1-GFP worked in nuclei to repress the GA
      signaling pathway; its overproduction caused a dwarf phenotype. Application of
      GA(3) to SLR1-GFP overproducers induced GA actions such as shoot elongation,
      downregulation of GA 20-oxidase expression, and upregulation of SLR1 expression
      linked with the disappearance of the nuclear SLR1-GFP protein. We also performed
      domain analyses of SLR1 using transgenic plants overproducing different kinds of
      truncated SLR1 proteins. The analyses revealed that the SLR1 protein can be
      divided into four parts: a GA signal perception domain located at the N terminus,
      a regulatory domain for its repression activity, a dimer formation domain
      essential for signal perception and repression activity, and a repression domain
      at the C terminus. We conclude that GA signal transduction is regulated by the
      appearance or disappearance of the nuclear SLR1 protein, which is controlled by
      the upstream GA signal.

PMID- 11826300
TI  - Uptake of a fluorescent marker in plant cells is sensitive to brefeldin A and
      wortmannin.
AB  - We assessed FM1-43 [N-(3-triethylammoniumpropyl)-4-(4
      [dibutylamino]styryl)pyridinium dibromide] as a fluorescent endocytosis marker in
      intact, walled plant cells. At 4 degrees C, FM1-43 stained the plasma membrane,
      and after 30 to 120 min of incubation at 26 degrees C, FM1-43 labeled cytoplasmic
      vesicles and then the vacuole. Fluorimetric quantitation demonstrated dye uptake
      temperature sensitivity (approximately 65% reduction at 16 degrees C, >90% at 4
      degrees C). FM1-43 uptake in suspension cells was stimulated more than twofold by
      brefeldin A and inhibited approximately 0.4-fold by wortmannin. FM1-43 delivery
      to the vacuole was largely inhibited by brefeldin A, although overall uptake was
      stimulated, and brefeldin A treatment caused the accumulation of large
      prevacuolar endosomal vesicles heavily labeled with FM1-43. Three-dimensional
      time lapse imaging revealed that FM1-43-labeled vacuoles and vesicles are highly
      dynamic. Thus, FM1-43 serves as a fluorescent marker for imaging and quantifying
      membrane endocytosis in intact plant cells.

PMID- 11826301
TI  - Arabidopsis RGL1 encodes a negative regulator of gibberellin responses.
AB  - In Arabidopsis, the DELLA subfamily of GRAS regulatory genes consists of GAI,
      RGA, RGA-LIKE1 (RGL1), RGL2, and RGL3. GAI and RGA are known to be negative
      regulators of gibberellin (GA) responses. We found that RGL1 is a similar
      repressor of GA responses, as revealed by RGL1 gain-of-function and loss-of
      function phenotypes. Repression of GA responses in Arabidopsis was conferred by a
      dominant 35S-rgl1 transgene carrying a DELLA domain deletion analogous to the GA
      insensitive gai-1 mutation. As in GA-deficient Arabidopsis, the transgenic plants
      were dark green dwarfs with underdeveloped trichomes and flowers. Expression
      levels of GA4, a feedback-regulated GA biosynthetic gene, were increased
      correspondingly. Conversely, a loss-of-function rgl1 line had reduced GA4
      expression and exhibited GA-independent activation of seed germination, leaf
      expansion, flowering, stem elongation, and floral development, as detected by
      resistance to the GA biosynthesis inhibitor paclobutrazol. RGL1 plays a greater
      role in seed germination than do GAI and RGA. The expression profile of RGL1
      differed from those of the four other DELLA homologs. RGL1 message levels were
      predominant in flowers, with transcripts detected in developing ovules and
      anthers. As with RGA, green fluorescent protein (GFP)-tagged RGL1 protein was
      localized to the nucleus, but unlike GFP-RGA, there was no degradation after GA
      treatment. These findings indicate that RGL1 is a partially redundant, but
      distinct, negative regulator of GA responses and suggest that all DELLA subfamily
      members might possess separate as well as overlapping roles in GA signaling.

PMID- 11826302
TI  - The Arabidopsis SPIKE1 gene is required for normal cell shape control and tissue
      development.
AB  - Regulated growth and cell shape control are fundamentally important to the
      function of plant cells, tissues, and organs. The signal transduction cascades
      that control localized growth and cell shape, however, are not known. To better
      understand the relationship between cytoskeletal organization, organelle
      positioning, and regulated vesicle transport, we conducted a forward genetic
      screen to identify genes that regulate cytoskeletal organization in plants.
      Because of the distinct requirements for microtubules and actin filaments during
      leaf trichome development, a trichome-based morphology screen is an efficient
      approach to identify genes that affect cytoplasmic organization. The seedling
      lethal spike1 mutant was identified based on trichome, cotyledon, and leaf-shape
      defects. The predicted SPIKE1 protein shares amino acid identity with a large
      family of adapter proteins present in humans, flies, and worms that integrate
      extracellular signals with cytoskeletal reorganization. Both the trichome
      phenotype and immunolocalization data suggest that SPIKE1 also is involved in
      cytoskeletal reorganization. The assembly of laterally clustered foci of
      microtubules and polarized growth are early events in cotyledon development, and
      both processes are misregulated in spike1 epidermal cells.

PMID- 11826304
TI  - The early phase change gene in maize.
AB  - Recessive mutations of the early phase change (epc) gene in maize affect several
      aspects of plant development. These mutations were identified initially because
      of their striking effect on vegetative phase change. In certain genetic
      backgrounds, epc mutations reduce the duration of the juvenile vegetative phase
      of development and cause early flowering, but they have little or no effect on
      the number of adult leaves. Except for a transient delay in leaf production
      during germination, mutant plants initiate leaves at a normal rate both during
      and after embryogenesis. Thus, the early flowering phenotype of epc mutations is
      explained completely by their effect on the expression of the juvenile phase. The
      observation that epc mutations block the rejuvenation of leaf primordia in
      excised shoot apices supports the conclusion that epc is required for the
      expression of juvenile traits. This phenotype suggests that epc functions
      normally to promote the expression of the juvenile phase of shoot development and
      to suppress the expression of the adult phase and that floral induction is
      initiated by the transition to the adult phase. epc mutations are epistatic to
      the gibberellin-deficient mutation dwarf1 and interact additively with the
      dominant gain-of-function mutations Teopod1, Teopod2, and Teopod3. Genetic
      backgrounds that enhance the mutant phenotype of epc demonstrate that, in
      addition to its role in phase change, epc is required for the maintenance of the
      shoot apical meristem, leaf initiation, and root initiation.

PMID- 11826303
TI  - A mutation in the Arabidopsis KT2/KUP2 potassium transporter gene affects shoot
      cell expansion.
AB  - Potassium ions (K(+)) are the most abundant cations in plants and are necessary
      for cell growth. Arabidopsis shy3-1 mutant plants have a short hypocotyl, small
      leaves, and a short flowering stem, and these defects result from decreased cell
      expansion. The semidominant shy3-1 mutation changes an amino acid in KT2/KUP2, a
      K(+) transporter related to the Escherichia coli Kup protein. Second mutations in
      the KT2/KUP2/SHY3 gene, including presumed null mutations, suppress the shy3-1
      phenotypes. Plants with these intragenic suppressor mutations appear similar to
      wild-type plants, suggesting that KT2/KUP2/SHY3 acts redundantly with other
      genes. Expression of the shy3-1 mutant version of KT2/KUP2/SHY3 in wild-type
      plants confers shy3-1-like phenotypes, indicating that shy3-1 probably either
      causes a gain of function or creates an interfering protein. The shy3-1 mutation
      does not eliminate the ability of the KT2/KUP2 cDNA to rescue the growth of a
      potassium transport-deficient E. coli mutant. A P(SHY3)::GUS fusion is expressed
      in growing portions of the plant. These results suggest that KT2/KUP2/SHY3
      mediates K(+)-dependent cell expansion in growing tissues.

PMID- 11826306
TI  - Mutation of a chitinase-like gene causes ectopic deposition of lignin, aberrant
      cell shapes, and overproduction of ethylene.
AB  - Chitinase-like proteins have long been proposed to play roles in normal plant
      growth and development, but no mutations in chitinase-like genes have been
      obtained previously to support this hypothesis. In this study, we have shown that
      the gene responsible for the elp1 mutation in Arabidopsis encodes a chitinase
      like protein (AtCTL1). Mutation of this chitinase-like gene caused ectopic
      deposition of lignin and aberrant shapes of cells with incomplete cell walls in
      the pith of inflorescence stems. The AtCTL1 gene was expressed in all organs
      during normal plant growth and development, but it was not induced by wounding,
      salicylic acid, pectin fragments, or ethylene. Consistent with its ubiquitous
      expression pattern, mutation of the AtCTL1 gene affected many aspects of plant
      growth and development, including exaggerated hook curvature, reduced length and
      increased diameter of hypocotyls in dark-grown seedlings, and reduced root length
      and increased number of root hairs in light-grown seedlings. The mutant
      phenotypes could be rescued partially by ethylene inhibitors, and ethylene
      production in the mutant was significantly greater than in the wild type.
      Together, these results suggest that AtCTL1, a chitinase-like gene, is essential
      for normal plant growth and development in Arabidopsis.

PMID- 11826305
TI  - Arabidopsis CAP regulates the actin cytoskeleton necessary for plant cell
      elongation and division.
AB  - An Arabidopsis cDNA (AtCAP1) that encodes a predicted protein of 476 amino acids
      highly homologous with the yeast cyclase-associated protein (CAP) was isolated.
      Expression of AtCAP1 in the budding yeast CAP mutant was able to rescue defects
      such as abnormal cell morphology and random budding pattern. The C-terminal
      domain, 158 amino acids of AtCAP1 possessing in vitro actin binding activity, was
      needed for the regulation of cytoskeleton-related defects of yeast. Transgenic
      plants overexpressing AtCAP1 under the regulation of a glucocorticoid-inducible
      promoter showed different levels of AtCAP1 accumulation related to the extent of
      growth abnormalities, in particular size reduction of leaves as well as petioles.
      Morphological alterations in leaves were attributable to decreased cell size and
      cell number in both epidermal and mesophyll cells. Tobacco suspension-cultured
      cells (Bright Yellow 2) overexpressing AtCAP1 exhibited defects in actin
      filaments and were unable to undergo mitosis. Furthermore, an immunoprecipitation
      experiment suggested that AtCAP1 interacted with actin in vivo. Therefore, AtCAP1
      may play a functional role in actin cytoskeleton networking that is essential for
      proper cell elongation and division.

PMID- 11826307
TI  - Functional dissection of a Rice Dr1/DrAp1 transcriptional repression complex.
AB  - We characterized rice cDNA sequences for OsDr1 and OsDrAp1, which encode
      structural homologs of the eukaryotic general repressors Dr1 and DrAp1,
      respectively. OsDr1 and OsDrAp1 are nuclear proteins that interact with each
      other and with the TATA binding protein/DNA complex. In vitro and in vivo
      functional analyses showed that OsDrAp1 functions as a repressor, unlike its role
      in other eukaryotic systems, in which DrAp1 is a corepressor. OsDr1 and OsDrAp1
      functioned together as a much stronger repressor than either one alone.
      Functional dissections revealed that the N-terminal histone-fold domains of OsDr1
      and OsDrAp1 were necessary and sufficient for their repression and protein
      protein interaction with each other. The unique glutamine- and proline-rich
      domain of OsDr1 had no repression activity. The basic amino acid-rich region and
      an arginine and glycine repeat domain of OsDrAp1 enhanced its repression
      activity. Thus, although OsDr1 and OsDrAp1 function as repressors, the functions
      of the two components are reversed compared with those of their nonplant
      counterparts.

PMID- 11826308
TI  - The rice cyclin-dependent kinase-activating kinase R2 regulates S-phase
      progression.
AB  - Cyclin-dependent kinases (CDKs) are the central components of eukaryotic cell
      cycle regulation. Phosphorylation of CDKs at a conserved threonine residue is
      required for their full activity and is mediated by a CDK-activating kinase
      (CAK). The CAK R2 from rice belongs to those CAKs that phosphorylate not only
      CDKs but also the C-terminal domain (CTD) of RNA polymerase II. We showed that R2
      is a nuclear protein with increased expression and increased CTD kinase activity
      in S-phase. Increasing R2 abundance through a transgenic approach accelerated S
      phase progression and overall growth rate in suspension cells. In planta, the CTD
      kinase activity of R2 was induced by a growth-promoting signal. R2 regulation,
      therefore, may constitute a plant-specific adaptive mechanism that is used to
      adjust the rate of cell proliferation in response to a changing environment.

PMID- 11826309
TI  - Central functions of the lumenal and peripheral thylakoid proteome of Arabidopsis
      determined by experimentation and genome-wide prediction.
AB  - Experimental proteome analysis was combined with a genome-wide prediction screen
      to characterize the protein content of the thylakoid lumen of Arabidopsis
      chloroplasts. Soluble thylakoid proteins were separated by two-dimensional
      electrophoresis and identified by mass spectrometry. The identities of 81
      proteins were established, and N termini were sequenced to validate localization
      prediction. Gene annotation of the identified proteins was corrected by
      experimental data, and an interesting case of alternative splicing was
      discovered. Expression of a surprising number of paralogs was detected.
      Expression of five isomerases of different classes suggests strong (un)folding
      activity in the thylakoid lumen. These isomerases possibly are connected to a
      network of peripheral and lumenal proteins involved in antioxidative response,
      including peroxiredoxins, m-type thioredoxins, and a lumenal ascorbate
      peroxidase. Characteristics of the experimentally identified lumenal proteins and
      their orthologs were used for a genome-wide prediction of the lumenal proteome.
      Lumenal proteins with a typical twin-arginine translocation motif were predicted
      with good accuracy and sensitivity and included additional isomerases and
      proteases. Thus, prime functions of the lumenal proteome include assistance in
      the folding and proteolysis of thylakoid proteins as well as protection against
      oxidative stress. Many of the predicted lumenal proteins must be present at
      concentrations at least 10,000-fold lower than proteins of the photosynthetic
      apparatus.

PMID- 11826310
TI  - Reevaluation of the effects of brefeldin A on plant cells using tobacco Bright
      Yellow 2 cells expressing Golgi-targeted green fluorescent protein and COPI
      antisera.
AB  - Brefeldin A (BFA) causes a block in the secretory system of eukaryotic cells by
      inhibiting vesicle formation at the Golgi apparatus. Although this toxin has been
      used in many studies, its effects on plant cells are still shrouded in
      controversy. We have reinvestigated the early responses of plant cells to BFA
      with novel tools, namely, tobacco Bright Yellow 2 (BY-2) suspension-cultured
      cells expressing an in vivo green fluorescent protein-Golgi marker, electron
      microscopy of high-pressure frozen/freeze-substituted cells, and antisera against
      Atgamma-COP, a component of COPI coats, and AtArf1, the GTPase necessary for COPI
      coat assembly. The first effect of 10 microg/mL BFA on BY-2 cells was to induce
      in <5 min the complete loss of vesicle-forming Atgamma-COP from Golgi cisternae.
      During the subsequent 15 to 20 min, this block in Golgi-based vesicle formation
      led to a series of sequential changes in Golgi architecture, the loss of distinct
      Golgi stacks, and the formation of an endoplasmic reticulum (ER)-Golgi hybrid
      compartment with stacked domains. These secondary effects appear to depend in
      part on stabilizing intercisternal filaments and include the continued maturation
      of cis- and medial cisternae into trans-Golgi cisternae, as predicted by the
      cisternal progression model, the shedding of trans-Golgi network cisternae, the
      fusion of individual Golgi cisternae with the ER, and the formation of large ER
      Golgi hybrid stacks. Prolonged exposure of the BY-2 cells to BFA led to the
      transformation of the ER-Golgi hybrid compartment into a sponge-like structure
      that does not resemble normal ER. Thus, although the initial effects of BFA on
      plant cells are the same as those described for mammalian cells, the secondary
      and tertiary effects have drastically different morphological manifestations.
      These results indicate that, despite a number of similarities in the trafficking
      machinery with other eukaryotes, there are fundamental differences in the
      functional architecture and properties of the plant Golgi apparatus that are the
      cause for the unique responses of the plant secretory pathway to BFA.

PMID- 11826311
TI  - Repair of damaged DNA by Arabidopsis cell extract.
AB  - All living organisms have to protect the integrity of their genomes from a wide
      range of genotoxic stresses to which they are inevitably exposed. However,
      understanding of DNA repair in plants lags far behind such knowledge in bacteria,
      yeast, and mammals, partially as a result of the absence of efficient in vitro
      systems. Here, we report the experimental setup for an Arabidopsis in vitro
      repair synthesis assay. The repair of plasmid DNA treated with three different
      DNA-damaging agents, UV light, cisplatin, and methylene blue, after incubation
      with whole-cell extract was monitored. To validate the reliability of our assay,
      we analyzed the repair proficiency of plants depleted in AtRAD1 activity. The
      reduced repair of UV light- and cisplatin-damaged DNA confirmed the deficiency of
      these plants in nucleotide excision repair. Decreased repair of methylene blue
      induced oxidative lesions, which are believed to be processed by the base
      excision repair machinery in mammalian cells, may indicate a possible involvement
      of AtRAD1 in the repair of oxidative damage. Differences in sensitivity to DNA
      polymerase inhibitors (aphidicolin and dideoxy TTP) between plant and human cell
      extracts were observed with this assay.

PMID- 11826314
TI  - Are certain practices at work a perk of the job or fraud?

PMID- 11826313
TI  - Increasing number of patients are being given wrong drugs.

PMID- 11826312
TI  - EDS5, an essential component of salicylic acid-dependent signaling for disease
      resistance in Arabidopsis, is a member of the MATE transporter family.
AB  - The eds5 mutant of Arabidopsis (earlier named sid1) was shown previously to
      accumulate very little salicylic acid and PR-1 transcript after pathogen
      inoculation and to be hypersusceptible to pathogens. We have isolated EDS5 by
      positional cloning and show that it encodes a protein with a predicted series of
      nine to 11 membrane-spanning domains and a coil domain at the N terminus. EDS5 is
      homologous with members of the MATE (multidrug and toxin extrusion) transporter
      family. EDS5 expression is very low in unstressed plants and strongly induced by
      pathogens and UV-C light. The transcript starts to accumulate 2 hr after
      inoculation of Arabidopsis with an avirulent strain of Pseudomonas syringae or UV
      C light exposure, and it stays induced for approximately 2 days. EDS5 also is
      expressed after treatments with salicylic acid, indicating a possible positive
      feedback regulation. EDS5 expression after infection by certain pathogens as well
      as after UV-C light exposure depends on the pathogen response proteins EDS1,
      PAD4, and NDR1, indicating that the signal transduction pathways after UV-C light
      exposure and pathogen inoculation share common elements.

PMID- 11826315
TI  - Patient dies after senior nurse failed to provide adequate staff.

PMID- 11826316
TI  - Factors influencing community nurses' treatment of leg ulcers.
AB  - Clinical effectiveness and evidence-based practice are a central feature of the
      clinical governance framework. Few studies have examined factors that motivate
      nurses to change practice in line with evidence-based guidelines. The overall aim
      of this exploratory study was to examine community nurses' experience of taking
      part in a clinical effectiveness programme for the management of leg ulcers in
      the community and to identify factors most likely to ensure a change in practice.
      The implementation programme was conducted in the general practices within one
      district of a primary care audit group. Face-to-face interviews were conducted
      with all practice nurses and district nurses involved in the care of patients
      with leg ulcers from the participating practices. Nurses identified the presence
      of a credible facilitator, visible benefits for patients and a desire to carry
      out their work in an evidence-based way as factors likely to influence change.
      However, the degree of change achieved was not uniform across all participants
      and three typologies of nurses were identified according to their attitudes and
      level of involvement.

PMID- 11826317
TI  - Legal aspects of consent. 19: Research/mentally competent adult.

PMID- 11826318
TI  - Providing a healthcare input to children in special schools.
AB  - The education of children with special educational needs is often accompanied by
      a requirement for medical or healthcare provision. If this cannot be done safely
      then the child's access to education is limited. No standardized template for the
      delivery of a healthcare input to children in special schools is apparent. This
      study sought to explore, through the use of an indepth needs assessment exercise
      and focus group interviews, what the most appropriate healthcare role was for
      delivering health care in a special school catering for children with a broad
      range of severe learning disabilities. While an overwhelming viewpoint of
      participants in focus groups perceived that a nurse was the only suitable person
      to undertake the role, the evidence gathered prompted the research steering group
      to suggest to the contrary, i.e. that the role of a healthcare worker with a
      national vocational qualification (NVQ) level 3 in care was the more appropriate
      person to maximize both the role of the nurse and the quality of care provided to
      these children.

PMID- 11826319
TI  - Value of employment to people with learning disabilities.
AB  - A key objective of the Government White Paper 'Valuing People: A New Strategy for
      Learning Disability for the 21st Century' is to encourage and assist people with
      learning disabilities to gain employment. This is because very few people with
      learning disabilities are in paid work and employment is promoted as a means of
      improving self-esteem, skills and social integration and acceptability. The aim
      of this article is to highlight some benefits of, and the risks and concerns
      around, people with learning disabilities undertaking paid work. Learning
      disability nurses need to be aware of these issues if they are to advise and
      support clients effectively. If people with learning disabilities are not able or
      unwilling to enter the world of work then alternative approaches are needed.
      Leisure has the potential to offer similar benefits as work to people with
      learning disabilities.

PMID- 11826320
TI  - Benchmarking best practice for external ventricular drainage.
AB  - Sharing of best practice and use of all available evidence is important in
      developing effective clinical guidelines for nursing practice. This can be
      achieved through benchmarking. Sharing of good practice and achieving consensus
      guidelines can avoid repetition of effort by nurses engaged in similar fields of
      practice. The Pan London Neuroscience Practice Development Forum was established
      in 1998 to share best practice within the field of neuroscience nursing across
      London. The Pan London Forum has now achieved consensus and developed evidence
      based clinical guidelines for the management of external ventricular drainage.
      Within the scope of this article, the principles of external ventricular drainage
      will be highlighted, before identifying the evidence base for nursing management
      of patients. Approaches for troubleshooting common problems will also be
      discussed and the benchmarked clinical guidelines will be presented.

PMID- 11826322
TI  - The importance of nursing values in interprofessional collaboration.
AB  - Nursing values are fundamental to the practice of nursing. They guide standards
      for action, provide a framework for evaluating behaviour and influence practice
      decisions. Despite the importance that can be attributed to nursing values,
      acknowledgement of them is difficult to find in the current debate about how
      interprofessional working is changing the healthcare system in which nurses
      currently work. This article argues that the profession needs to demonstrate that
      values are not only a theoretical concept but also that they can, and do, have a
      profound impact on the practical working life of nurses delivering care in
      collaboration with other professions.

PMID- 11826321
TI  - Outcome measures for erectile dysfunction. 1: Literature review.
AB  - This article describes and evaluates critically the outcome measures available
      for the assessment of the conservative treatment of erectile dysfunction (ED).
      The literature review identified 26 outcome measures. Of these, 14 were
      subjective and 12 were objective. Objective measures can provide more accurate
      information. However, owing to the sensitive nature of the problem,
      questionnaires which are reliable and sensitive to change can provide valuable
      data. Different outcome measures were needed for each of the separate components
      of ED. These components were found to be rigidity, vascular flow, nerve
      conductivity, intracavemosal pressure, ischiocavernosus muscle power, partner
      satisfaction and quality of life. An evaluation of outcome measures for each
      component of ED is provided in the second part of this article. Quick, simple,
      inexpensive and efficient outcome measures can be used by nurses to evaluate the
      impact of conservative treatment for ED.

PMID- 11826323
TI  - Heart on the hill 2002.

PMID- 11826324
TI  - Dyslipidemia prevention and control in Canada: the national lipid strategy.

PMID- 11826325
TI  - Mirrors in the dark.

PMID- 11826326
TI  - Multitasking and the technical quality of the electrocardiogram.
AB  - BACKGROUND: The electrocardiogram (ECG) is a powerful clinical tool for
      diagnosing cardiac abnormalities. Proper ECG data acquisition is essential
      because it allows physicians to interpret ECG results accurately and efficiently.
      This is especially important for patients with acute myocardial infarction, so
      that they can receive early treatment. As a result of multitasking, ECGs are
      acquired by two groups of personnel at the University of Alberta Hospital,
      Edmonton - ECG technologists and non-ECG technologists. OBJECTIVE: To evaluate
      the effectiveness and quality of ECG acquisition at the University of Alberta
      Hospital site. METHODS: All adult ECGs acquired at the University of Alberta
      Hospital site from January 1 to June 30, 2000 were assessed. An ECG was
      classified as unacceptable if it lacked demographics identifying the patient,
      and/or it was of such poor technical quality that the interpretation was
      compromised. RESULTS: Of 25,509 ECGs acquired during this period, 13,849 (54%)
      and 11,660 (46%) ECGs were acquired by ECG technologists and non-ECG
      technologists, respectively. Eleven ECGs (0.08%) acquired by the ECG
      technologists and 3683 ECGs (32%) acquired by the non-ECG technologists were of
      unacceptable quality. The technical cost spent on these unacceptable ECGs is
      approximately $100,000 a year at this institution. CONCLUSIONS: Multitasking has
      resulted in a high rate of unacceptable ECGs. There is a significant difference
      in the effectiveness and quality of ECG acquisition performed by ECG
      technologists and non-ECG technologists. Poorly acquired ECGs impede proper
      diagnosis for patients, subject the institution to potential medical legal
      consequences and add an unnecessary burden to the health care budget.

PMID- 11826327
TI  - Angiotensin II fails to induce preconditioning in vivo--the protective role of
      myocardial stretch due to pressure overload.
AB  - BACKGROUND: Angiotensin II (Ang) has been successfully used as a preconditioning
      analogue in isolated rabbit hearts. It is also known that local concentrations of
      Ang accelerate ischemic injury in vivo, while activation of stretch receptors
      protects ischemic hearts. OBJECTIVES: First, to investigate further whether Ang
      can mimic preconditioning in vivo. Second, to test the hypothesis that there is
      an activation of stretch receptors, and that the larger infarct from the left
      atrium Ang compared with that from the intravenous Ang may be associated with the
      ischemic injury caused by local administration. METHODS: Male rabbits were
      divided into four groups - a control group, an ischemic preconditioning group
      with 5 min ischemia, a left atrial group and an intravenous group with 5 min Ang
      infusion. All animals were subjected to prolonged ischemia and reperfusion. A
      second series of experiments was also performed with five groups that had a 5 min
      mechanical obstruction of the aorta (Ao clamp), also used as a preconditioning
      analogue with or without the stretch receptor blocker gadolinium (Gd). RESULTS:
      Contrary to what was expected from the ex vivo experiments, Ang failed to mimic
      preconditioning (infarct size 39.6 6.1%, 13.7 4.1%, 52.2% 6.9% and 31.2 4.8%,
      respectively for the above groups). Interestingly, however, when Ang was infused
      intravenously, it produced a significantly smaller infarct compared with that
      observed after the same dose was infused into the left atrium (P<0.05). The
      infarct size was 17.0 3.7% in the Ao clamp group, which was an effect completely
      prevented by Gd (45.8 4.2%, P<0.01). Although Gd did not alter infarct size in
      the control and ischemic preconditioning groups, it increased infarct size when
      added to the intravenous Ang group (Gd-intravenous Ang 48.6 3.3%, P<0.05 compared
      with intravenous Ang). CONCLUSIONS: Ang fails to mimic preconditioning in vivo,
      but salvage of ischemic myocardium can be emanated from pressure overload.

PMID- 11826328
TI  - New use of antiarrhythmia drugs in Saskatchewan.
AB  - BACKGROUND: Cardiac dysrhythmias are a diverse group of disorders and many are
      associated with significant morbidity and mortality. Because their recent
      therapeutic management has not been adequately described, this study details the
      antiarrhythmia drugs that were dispensed to patients who had not received therapy
      in the preceding two years, and it evaluates the potential indications for the
      drugs as well as whether the therapy is consistent with the recommended
      procedures. METHODS: Patients who were dispensed a [Vaughn Williams?] class I or
      class III antiarrhythmia drug in 1993 or 1994, but not during the two previous
      years, were identified from the Saskatchewan prescription drug datafile. The drug
      data were linked with other information that was obtained from the provincial
      administrative health care utilization datafiles. Further clinical data were
      obtained from hospital charts and, to a limited extent, from physicians' records.
      RESULTS: Most patients were elderly (median age of 70 years) and were men
      (58.0%), although sotalol was prescribed more frequently to women (53.0%). A
      potential indication was identified for 63.8% of the patients and, of these, the
      most common was atrial fibrillation (65.3%). Almost half of the patients had a
      history of myocardial infarction, congestive heart failure or cardiomyopathy, and
      one-quarter of those were treated with amiodarone. CONCLUSIONS: While it is not
      possible to prove a direct link, the results of the present study are broadly
      consistent with the 'evidence-based' lessons of the Cardiac Arrhythmia
      Suppression Trial and other studies. The increasing use of propafenone, however,
      may indicate a lack of appreciation for the fact that, as a class IC drug, there
      is at least the potential for an adverse outcome when propafenone is used in
      patients with structural heart disease.

PMID- 11826329
TI  - Diagnostic endomyocardial biopsy pathology--general biopsy considerations, and
      its use for myocarditis and cardiomyopathy: a review.
AB  - Endomyocardial biopsy is a commonly performed procedure used for the evaluation
      of myocardial tissues. Biopsies may be used to monitor transplant rejection, but
      they have many other applications, such as the evaluation of myocarditis,
      cardiomyopathy, drug toxicity, chest pain, arrhythmia and cardiac involvement by
      systemic diseases or neoplasms. The present paper discusses practical suggestions
      for biopsy interpretation, and the clinicopathological considerations for
      biopsies from patients with myocarditis and cardiomyopathies.

PMID- 11826330
TI  - Assessment of diastolic dysfunction after acute myocardial infarction using
      Doppler echocardiography.
AB  - Doppler echocardiography (DE) is becoming a powerful noninvasive tool for
      assessing left ventricular diastolic dysfunction after myocardial infarction
      (MI). Transmitral inflow DE measurements of early and late filling velocities,
      early to late ratio and early deceleration time correlate well with left
      ventricular filling pressure. Three abnormal filling patterns (impaired
      relaxation, pseudonormalization and restrictive) develop after MI, depending on
      infarct size. Pulmonary venous inflow DE contributes important additional
      diagnostic data and, when combined with transmitral DE, avoids potential
      confusion due to the pseudonormal pattern that develops in the presence of high
      left atrial pressure and impaired relaxation. Several studies indicate that these
      DE patterns correlate with progressively increasing functional impairment, and
      the restrictive transmitral pattern predicts heart failure and death among MI
      survivors. Further studies are needed to evaluate the effects of therapy on the
      DE patterns of diastolic dysfunction after MI.

PMID- 11826331
TI  - Left atrial mass.

PMID- 11826333
TI  - A randomized survey of the preference of gastroenterologists for a Cochrane
      review versus a traditional narrative review.
AB  - BACKGROUND: Clinicians often rely on review material rather than analysis of
      primary research to guide therapy. Systematic reviews use methods to insure
      thoroughness and to minimize bias, but many clinicians are not familiar with
      systematic reviews and continue to rely on narrative reviews. OBJECTIVES: To
      determine whether a traditional narrative review or a systematic review is
      perceived to be more useful. METHODS: A clinical scenario (patient with chronic
      Crohn's disease considered for azathioprine therapy) was circulated to
      gastroenterologists, along with a narrative review of therapy (including
      azathioprine) for inflammatory bowel disease written by an acknowledged expert,
      or with a systematic Cochrane review of the use of azathioprine for this disease.
      Whether knowledge of authorship and journal source influences the perception of
      usefulness of a narrative review was investigated. RESULTS: The Cochrane review
      was rated significantly more highly than the narrative review on a 100 mm visual
      analogue scale (21.3 mm; 95% CI 14.5 to 28 mm). The proportion of respondents who
      considered the review to be a useful guide was also higher in the group that
      received the Cochrane review (91%) than in the group that received the narrative
      review, with author and journal concealed (62%) or identified (70%) (P<0.001 for
      both comparisons). Ratings from the two groups that received the narrative review
      were not significantly different. CONCLUSIONS: The focused systematic review was
      perceived to be more useful than a traditional broad narrative review as a guide
      to making a decision concerning the use of specific therapy. The possible
      strengths of systematic reviews should be more fully investigated. If there is
      additional evidence supporting their greater value to clinicians, they should be
      made more widely available to clinicians and their strengths should be
      publicized.

PMID- 11826334
TI  - Spontaneous free perforation of the small intestine in Crohn's disease.
AB  - Spontaneous free perforation of the small intestine is a rare but often dramatic
      event in the clinical course of Crohn's disease. Fifteen new cases of spontaneous
      free perforation of the small intestine--nine female patients and six male
      patients--were discovered in a series of 1000 consecutively evaluated patients
      with Crohn's disease seen during a period spanning 20 years, for an estimated
      frequency of 1.5%. Spontaneous free perforation was the presenting clinical
      feature of Crohn's disease in nine (60%) of the newly discovered cases. Most
      perforations were located in the ileum rather than in the jejunum, and there were
      no duodenal free perforations. One patient with extensive intestinal disease
      presented with concomitant free perforations of the jejunum and ileum, while a
      second patient had two free ileal perforations that developed independently,
      separated by about six years. No perforations were the result of a superimposed
      malignant process, ie, adenocarcinoma or lymphoma. There have been no
      mortalities, and the subsequent clinical course of these patients has been
      limited to a minority requiring corticosteroid or immunosuppressive medications,
      or further surgical resections.

PMID- 11826335
TI  - Two for one: coexisting ulcerative colitis and Crohn's disease.
AB  - Three cases of coexisting ulcerative colitis and Crohn's disease are presented.
      In the first case, the patient had a long-standing history of ulcerative
      proctitis before developing Crohn's colitis. In the two remaining cases, the
      patients presented initially with Crohn's disease of the ileum and, subsequent to
      resection, developed ulcerative colitis. Well-documented cases of patients
      diagnosed with both ulcerative colitis and Crohn's disease are rare. The
      literature on such cases is reviewed, and the controversy over whether ulcerative
      colitis and Crohn's disease are two distinct diseases is explored.

PMID- 11826336
TI  - Evidence-based medicine: a resource for all.

PMID- 11826337
TI  - Interaction of the Canadian Association of Gastroenterology with industry.

PMID- 11826338
TI  - A case of missing identity.

PMID- 11826339
TI  - Hepatitis B viral mutants and their relevance to the Canadian health care system.
AB  - Over the past 10 years, an increasing number of mutations in the hepatitis B
      virus genome have been described. While the majority of these mutations appear to
      be 'silent' or not clinically relevant, some have been described in association
      with increased severity of disease (core and basic core promoter mutations),
      evasion of immunological surveillance (S escape mutants), hepatocellular
      carcinogenesis (X mutants) and resistance to antiviral agents (DNA polymerase
      mutations). The molecular events and the clinical consequences thereof are
      reviewed.

PMID- 11826340
TI  - Risks and benefits of Helicobacter pylori eradication: current status.
AB  - In patients with diseases known to be associated with Helicobacter pylori
      infection, such as peptic ulcer, treatment of the underlying infection is the
      standard of care. However, in most major consensus management guidelines,
      including those published in Canada, widespread testing for H pylori infection is
      not recommended. This practice is not encouraged because of insufficient evidence
      of cost-benefit in gastric cancer prevention, the potential for increases in
      antibiotic resistance and the controversial hypothesis of potential negative
      effects of eradication in certain clinical entities. For example, there is
      insufficient evidence to recommend against eradicating H pylori discovered in a
      patient with symptoms of gastroesophageal reflux disease. The management
      guidelines designed specifically in Canada should, therefore, continue to be
      applied, with H pylori diagnosed and treated in appropriately selected patients.

PMID- 11826341
TI  - Post-liver transplantation immunosuppression: the song does not remain the same.

PMID- 11826342
TI  - CAG interactive lecture series: a Web-based learning program.

PMID- 11826344
TI  - Epworth's sleepiness scale in outpatients with different values of arterial blood
      pressure.
AB  - OBJECTIVE: To compare sleepiness scores of the Epworth scale in patients with
      different levels of arterial pressure when undergoing outpatient monitoring
      within the context of clinical evaluation. METHODS: A total of 157 patients
      selected for outpatient monitoring of arterial pressure during hypertension
      evaluation were divided into 3 groups: group 1 - normotensive; group 2 -
      hypertensive; group 3 - resistant hypertensive. For analysis, values >/=11 were
      considered as associated with respiratory disturbances during sleep. RESULTS:
      Seventeen (10.8%) patients in group 1, 112 (71.3%) in group 2, and 28 (17.8%) in
      group 3, which was composed of aged, more severely hypertensive individuals, were
      analyzed. Groups were similar relative to sex and body mass index, but different
      in relation to systolic and diastolic pressure levels and age. Despite an
      absolute difference, no statistically significant difference occurred between
      Epworth scores and in the proportion of patients with values >/=11 (5.9% vs.
      18.8% vs. 212.4%; P=0.37). Despite the positive association between degree of
      sleepiness measured with the scale and the severity of the hypertension, no
      statistical significance occurred following control by age (p=0.18). CONCLUSION:
      A positive correlation exists between degree of sleepiness and hypertension
      severity. The absence of a statistical significance shown in the present study
      could be due to a beta type of error. Instruments that render this complaint into
      an objective finding could help in the pursuit of an investigation of respiratory
      disturbances during sleep in more severely hypertensive patients, and should
      therefore be studied better.

PMID- 11826343
TI  - Useful clinical features for the selection of ideal patients with atrial
      fibrillation for mapping and catheter ablation.
AB  - OBJECTIVE: To identify useful clinical characteristics for selecting patients
      eligible for mapping and ablation of atrial fibrillation. METHODS: We studied 9
      patients with atrial fibrillation, without structural heart disease, associated
      with: 1) antiarrhythmic drugs, 2) symptoms of low cardiac output, and 3)
      intention to treat. Seven patients had paroxysmal atrial fibrillation and 2 had
      recurrent atrial fibrillation. RESULTS: In the 6 patients who underwent mapping
      (all had paroxysmal atrial fibrillation), catheter ablation was successfully
      carried out in superior pulmonary veins in 5 patients (the first 3 in the left
      superior pulmonary vein and the last 2 in the right superior pulmonary vein). One
      patient experienced a recurrence of atrial fibrillation after 10 days. We
      observed that patients who had short episodes of atrial fibrillation on 24-hour
      Holter monitoring before the procedure were those in whom mapping the focus of
      tachycardia was possible. Tachycardia was successfully suppressed in 4 of 6
      patients. The cause of failure was due to the impossibility of maintaining sinus
      rhythm long enough for efficient mapping. CONCLUSION: Patients experiencing short
      episodes of atrial fibrillation during 24-hour Holter monitoring were the most
      eligible for mapping and ablation, with a final success rate of 66%, versus the
      global success rate of 44%. Patients with persistent atrial fibrillation were not
      good candidates for focal ablation.

PMID- 11826345
TI  - Lipid metabolism in rats fed diets containing different types of lipids.
AB  - OBJECTIVE: To assess the effect of different types of lipid diets on the lipid
      metabolism of aging rats. METHODS: Fifty male Wistar rats were studied from the
      time of weaning to 12 and 18 months of age. Their diets were supplemented as
      follows: with soybean oil (S), canola oil (CA), lard and egg yolk (LE), and
      canola oil + lard and egg yolk (CA + LE). Blood pressure (BP) was measured every
      month, and the heart/body ratio (H/BR) was determined. The rats were euthanized
      at the age of 12 and 18 months, and blood samples were collected for lipid
      analysis as follows: total cholesterol (TC), LDL-C, VLDL-C, HDL-C, triglycerides
      (TG), and glucose. RESULTS: The type of oil ingested by the animals significantly
      altered BP, H/BR, and serum lipid levels in rats at 12 and 18 months. No
      difference was observed in the survival curve of the animals in the different
      groups. The LE group had the highest BP, and the CA group was the only one in
      which BP did not change with aging. A reduction in the H/BR was observed in the
      LE and CA+LE animals. At the age of 12 months, differences in TC, HDL-C, LDL-C,
      VLDL-C, TG, and glucose were observed. At the age of 18 months, a significant
      difference in TC, HDL-C, and glucose was observed. The highest TC value was found
      in the CA group and the lowest in the S group. CONCLUSION: No increase in BP
      occurred, and an improvement was evident in the lipid profile of rats fed a diet
      supplemented with CA, in which an elevation in HDL-C levels was observed, as
      compared with levels with the other types of diet.

PMID- 11826346
TI  - Ventricular resynchronization through biventricular cardiac pacing for the
      treatment of refractory heart failure in dilated cardiomyopathy.
AB  - OBJECTIVE: The biventricular pacing (BVP) approach has good results in the
      treatment of congestive heart failure (CHF) in patients (pts) with disorders of
      intraventricular conduction. METHODS: We have applied BVP to 28 pts, with left
      ventricular pacing using minitoracotomy in 3 pts and the transvenous approach via
      coronary sinus in 25 pts. The mean duration of the QRS complexes was 187 ms, in
      the presence of the left branch block in 22 pts, and right branch block +
      divisional hemiblock in 6 pts. All pts had been considerated candidates to
      cardiac transplantation, and were under optimized drug therapy. Sixteen pts were
      in Functional Class (NYHA) IV, and 12 in class III. The ejection fraction varied
      from 22 to 46% (average = 34%). The pacing mode employed was biventricular triple
      chamber in 22 pts, and bi-ventricular dual-chamber in 6 pts (one with ICD).
      RESULTS: The pts were followed up for a period that ranged from 10 days to 14
      months (mean 5 months). All pts presented clinical improvement after implant,
      changing the NYHA Functional Class at the end of follow-up to Class I (9pts),
      Class II (10 pts) and Class III (6 pts). The initial mean ejection fraction have
      raised to 37%. Two pts died suddenly. One patient died due to a pulmonary fungal
      infection. CONCLUSION: Ventricular resynchronization through BVP, improved
      significantly the Functional Class and, therefore, the quality of life.
      Assessments of myocardial function acutely performed do not reflect the clinical
      improvement observed.

PMID- 11826347
TI  - Cardiovascular assessment of patients with Ullrich-Turner's Syndrome on Doppler
      echocardiography and magnetic resonance imaging.
AB  - OBJECTIVE: To assess the cardiovascular features of Ullrich-Turner's syndrome
      using echocardiography and magnetic resonance imaging, and to correlate them with
      the phenotype and karyotype of the patients. The diagnostic concordance between
      the 2 methods was also assessed. METHODS: Fifteen patients with the syndrome were
      assessed by echocardiography and magnetic resonance imaging (cardiac chambers,
      valves, and aorta). Their ages ranged from 10 to 28 (mean of 16.7) years. The
      karyotype was analyzed in 11 or 25 metaphases of peripheral blood lymphocytes, or
      both. RESULTS: The most common phenotypic changes were short stature and
      spontaneous absence of puberal development (100%); 1 patient had a cardiac
      murmur. The karyotypes detected were as follows: 45,X (n=7), mosaics (n=5), and
      deletions (n=3). No echocardiographic changes were observed. In regard to
      magnetic resonance imaging, coarctation and dilation of the aorta were found in 1
      patient, and isolated dilation of the aorta was found in 4 patients. CONCLUSION:
      The frequencies of coarctation and dilation of the aorta detected on magnetic
      resonance imaging were similar to those reported in the literature (5.5% to 20%,
      and 6.3% to 29%, respectively). This confirmed the adjuvant role of magnetic
      resonance imaging to Doppler echocardiography for diagnosing cardiovascular
      alterations in patients with Ullrich-Turner's syndrome.

PMID- 11826349
TI  - Ambulatory blood pressure monitoring of patients with heart failure. A new
      prognosis marker.
AB  - OBJECTIVE: To evaluate the relationship between 24-hour ambulatory arterial blood
      pressure monitoring and the prognosis of patients with advanced congestive heart
      failure. METHODS: We studied 38 patients with NYHA functional class IV congestive
      heart failure, and analyzed left ventricular ejection fraction, diastolic
      diameter, and ambulatory blood pressure monitoring data. RESULTS: Twelve deaths
      occurred. Left ventricular ejection fraction (35.2 +/-7.3%) and diastolic
      diameter (72.2 +/- 7.8mm) were not correlated with the survival. The mean 24-hour
      (SBP24), waking (SBPw), and sleeping (SBPs) systolic pressures of the living
      patients were higher than those of the deceased patients and were significant for
      predicting survival. Patients with mean SBP24, SBPv, and SBPs >/=105mmHg had
      longer survival (p=0.002, p=0.01 and p=0.0007, respectively). Patients with
      diastolic blood pressure sleep decrements (dip) and patients with mean blood
      pressure dip </= 6mmHg had longer survival (p=0.04 and p=0.01, respectively). In
      the multivariate analysis, SBPs was the only variable with an odds ratio of 7.61
      (CI: 1.56; 3704) (p=0.01). Patients with mean SBP<105mmHg were 7.6 times more
      likely to die than those with SBP >/= 105 mmHg CONCLUSION: Ambulatory blood
      pressure monitoring appears to be a useful method for evaluating patients with
      congestive heart failure.

PMID- 11826348
TI  - An analysis of electrocardiographic criteria for determining left ventricular
      hypertrophy.
AB  - OBJECTIVE: To determine the most sensitive criterion for the detection of left
      ventricular hypertrophy according to echocardiographically defined left
      ventricular mass. METHODS: The Sokolow-Lyon voltage, Sokolow-Lyon-Rappaport,
      Cornell voltage duration product, White-Bock, and Romhilt-Estes point scoring
      criteria were compared with left ventricular mass index, corrected for body
      surface, obtained from the echocardiograms of 306 outpatients (176 females, 130
      males), of all age groups. RESULTS: The Cornell voltage duration product criteria
      index had the greatest sensitivity in women (54.90%), and the Sokolow-Lyon
      Rappaport index was most sensitive in men (73.53%). When applied to men at the
      same voltage amplitude (20mm) as that in women, the Cornell index showed
      increased sensitivity relative to the conventional index (28mm) of 67.65%
      (P</=0.01) and a sensitivity similar to that of the Sokolow-Lyon-Rappaport index,
      with higher specificity (P</=0.01). The White-Bock and Romhilt-Estes criteria
      were the least sensitive in men and women, despite their high specificity. The
      electrocardiographic criteria were more efficient when dilatation predominated
      over left ventricular hypertrophy. CONCLUSION: The Cornell index had greater
      sensitivity in women, and the Sokolow-Lyon-Rappaport index was more sensitive in
      men. When applied to men at the same voltage amplitude as that of women, the
      Cornell index had an increase in sensitivity similar to that of the Sokolow-Lyon
      Rappaport index.

PMID- 11826350
TI  - The use of abciximab associated with primary angioplasty for treating acute
      myocardial infarction.
AB  - OBJECTIVE: To assess the benefit resulting from the use of abciximab associated
      with primary angioplasty. The following parameters were analyzed in-hospital, at
      30 days, and 6 months: (a) flow in the culprit artery; (b) ventricular function;
      (c) combined outcome of death, acute myocardial infarction, and additional
      revascularization. METHODS: From November 1997 to June 1999, a longitudinal
      nonrandomized study with historical data of 137 patients with acute myocardial
      infarction within the first 12 hours. Patients undergoing primary angioplasty and
      were divided into 2 groups: those receiving (A) abciximab (26) or (B)
      conventional therapy (111). TIMI flow and regional ventricular function estimated
      by the standard deviation (SD)/chordis index were analyzed. RESULTS: At the end
      of angioplasty, TIMI 3 flow was observed in 76.9% and 83.8% of the patients in
      groups A and B, respectively (P=0.58). In the reevaluation, patients with TIMI
      flow <3 showed a 100% improvement in group A and a 33% in group B (P<0.0001). A
      significant improvement (P<0.0001) in regional ventricular function, by
      SD/chordis index, occurred in each group; no significant difference between
      groups however, was observed (29.9% x 20.2%; P=0.58). A nonsignificant reduction
      in the combined outcome in the in-hospital phase (3.85% A x 9.0% B; P=0.34) and
      on the 30th day (4.0% x 12.0%; P=0.22) was observed in group A. CONCLUSION:
      Abciximab improved blood flow. Primary angioplasty improved regional ventricular
      function independent of antithrombotic therapy. Abciximab showed a trend toward
      reducing the combined outcome in the in-hospital phase and on the 30th day.

PMID- 11826351
TI  - Increase in mortality due to myocardial infarction in the Brazilian city of Sao
      Paulo during winter.
AB  - OBJECTIVE: To study the seasonal variation in mortality due to myocardial
      infarction in the city of Sao Paulo. METHODS: We analyzed the database of PROAIM
      (Programa de Aprimoramento de Informacoes de Mortalidade) containing the
      registrations of the certificates of deaths due to myocardial infarction
      (International Classification of Diseases, 10th edition, classification I21) of
      the residents of the municipality of Sao Paulo during 12 months (from December
      1996 to November 1997). The number of deaths was corrected for a standard period
      of 90 days and then it was divided by the corresponding population to obtain the
      event rate per 10 thousand inhabitants. The magnitude of the seasonal variation,
      which was defined by the difference of the relative risks between the seasons
      with higher and lower mortality, was estimated. RESULTS: A total of 5,615 deaths
      due to myocardial infarction were included in the study. Sixty-one per cent
      occurred in the male sex, and the mean age was 68 years. The mortality rate
      during winter was always higher and that during summer was lower than that during
      the other seasons (P<0.01), independent from age and sex. Seasonal variations in
      deaths due to myocardial infarction was 30% in the general group, being 23% in
      individuals who died younger than 75 years, and 44% in the older ones.
      CONCLUSION: A marked seasonal variation in mortality due to myocardial infarction
      was observed in the city of Sao Paulo, with a significant increase in its
      magnitude and age distribution during the winter, similar to those reported in
      regions of North America and Europe with temperate climates.

PMID- 11826352
TI  - Biventricular pacing improves clinical behavior and reduces prevalence of
      ventricular arrhythmia in patients with heart failure.
AB  - PURPOSE: To analyze the influence of biventricular pacing (BP) on clinical
      behavior, ventricular arrhythmia (VA) prevalence, and left ventricular ejection
      fraction (LV EF) by gated ventriculography. METHODS: Twenty-four patients with
      left bundle branch block (LBBB) and NYHA class III and IV underwent pacemaker
      implantation and were randomized either to the conventional or BP group, all
      receiving BP after 6 months. RESULTS: Sixteen patients were in NYHA class IV
      (66.6%) and 8 were in class III (33.4%). After 1-year follow-up, 14 patients were
      in class II (70%) and 5 were in class III (25%). Two sudden cardiac deaths
      occurred. A significant reduction in QRS length was found with BP (p=0.006). A
      significant statistical increase, from a mean of 19.13 +/- 5.19% (at baseline) to
      25.33 +/- 5.90% (with BP) was observed in LVEF Premature ventricular contraction
      prevalence decreased from a mean of 10,670.00 +/- 12,595.39 SD or to a mean of
      3,007.00 +/- 3,216.63 SD PVC/24 h with BP (p<0.05). Regarding the hospital
      admission rate over 1 year, we observed a significant reduction from 60. To 16
      admissions with BP (p<0.05). CONCLUSION: Patients with LBBB and severe heart
      failure experienced, with BP, a significant NYHA class and LVEF improvement. A
      reduction in the hospital admission rate and VA prevalence also occurred.

PMID- 11826353
TI  - Primary coronary angioplasty in a nonagenarian.
AB  - A woman aged 98 years entered the tertiary hospital service with a picture of
      acute myocardial infarction of the extensive anterior wall, which began 4 hours
      earlier. Due to the large myocardial risk area suggested by the
      electrocardiogram, the patient was taken to the hemodynamics laboratory for the
      performance of emergency coronary arteriography, which revealed occlusion in the
      proximal third of the anterior descending artery. Primary angioplasty followed by
      stent grafting was successfully performed. The patient had a satisfactory
      evolution (Killip I) and was discharged from the hospital on the seventh
      postinfarction day. We discuss here aspects of thrombolysis and coronary
      percutaneous interventions in the aged.

PMID- 11826354
TI  - Obstruction of the left ventricular outflow tract after mitral valvuloplasty with
      implantation of Gregori's ring.
AB  - Mitral valvuloplasty is efficient for repairing mitral valve disease with few
      complications. In some cases, obstruction of the left ventricular outflow tract
      may occur due to systolic anterior motion of the mitral valve. We report the case
      of a patient with this complication and a pressure gradient between the left
      ventricle and the aorta of 130 mm Hg after mitral valvuloplasty with implantation
      of a Gregori's ring. The management was clinical with suspension of the
      vasoactive drugs and introduction of a beta-blocker. Two years after the surgery,
      the patient is asymptomatic and has a normal life.

PMID- 11826355
TI  - [Clinical-radiographic correlation. Case 1/2002: Instituto do Coracao do Hospital
      das Clinicas da FMUSP].

PMID- 11826356
TI  - Anatomicopathological evidence of the beginning of atherosclerosis in infancy and
      adolescence.

PMID- 11826357
TI  - Review of some causes of stillbirth.
AB  - Stillborn fetuses commonly demonstrate three mechanisms of death: hydrops,
      asphyxia, or shock. For each mechanism, the autopsy can discover any of multiple
      etiologies. This paper reviews the etiologies and pathogeneses of fetal death
      from that perspective.

PMID- 11826358
TI  - Early postnatal dexamethasone diminishes transforming growth factor alpha
      localization within the ileal muscularis propria of newborn mice and extremely
      low-birth-weight infants.
AB  - Focal small bowel perforation (FSBP) occurs most commonly in the ileum of
      extremely low-birth-weight (ELBW) infants. Early postnatal dexamethasone (EPD)
      administration results in an increased risk for FSBP in this patient population,
      but the mechanism by which this occurs is unknown. Infants with FSBP have healthy
      mucosa but thinned smooth muscle, suggesting a mechanism involving the muscularis
      propria for these perforations. One explanation for these findings would be that
      dexamethasone alters the tissue availability of pertinent growth factors to the
      smooth muscle. To explore this possibility, we administered dexamethasone or
      saline by intraperitoneal injection to newborn mice for 3 days (dosed at 1
      microg/g of body weight/day) to simulate EPD protocols. The animals were
      sacrificed after 72 h of treatment and their ileums harvested and prepared for
      microscopy. Immunolocalization was performed for three related growth factors
      (epidermal growth factor [EGF], heparin-binding EGF [h-EGF], and transforming
      growth factor alpha [TGF-alpha]) and their common receptor. We found TGF-alpha to
      be abundant and discretely localized in the muscularis propria in control animals
      but to be diminished in dexamethasone-treated animals. EGF-receptor
      immunostaining was also decreased with dexamethasone but there was minimal to no
      detection of EGF or h-EGF in either treatment condition. Surgical and autopsy
      specimens of the ileum were obtained from seven ELBW infants who either received
      EPD or not. These tissues were used for immunolocalization of the same growth
      factors and similar distributions for TGF-alpha were observed in several of these
      cases. These findings are consistent with an autocrine role for TGF-alpha in
      ileal smooth muscle proliferation and suggest a mechanism by which EPD might
      mediate smooth muscle thinning.

PMID- 11826359
TI  - Splenic arteries and veins in pediatric sickle cell disease.
AB  - The goal of this study was to verify the existence and prevalence of large vessel
      lesions outside the central nervous system in young patients with sickle cell
      disease. Thus, 17 spleens resected because of episodes of sequestration or
      infarction and 41 controls were studied. Anomalies of arteries and veins were
      detected in all spleens from sickle cell disease patients, but no definite
      correlation with age, sex, type of sickle hemoglobin, or frequency of
      sequestration episodes could be established. The most consistent lesions were
      intimal proliferation affecting large arteries and veins, reduplication of the
      internal elastic lamina of large arteries, and a lesion not previously documented
      in this condition, that of subendothelial infiltration of the large veins by
      activated T cells. Endotheliitis showing some similarity with the one seen in
      sickle cell disease spleens was noted in 5 of 41 spleens of patients who did not
      suffer from sickle cell disease. However, when present it was usually mild. Very
      limited damage to the arterial elastica was noted in only 1 of the 41 controls.
      Minimal endothelial proliferation was seen in 2 of 41 controls.

PMID- 11826360
TI  - Choroid plexus carcinomas and rhabdoid tumors: phenotypic and genotypic overlap.
AB  - Five of six poorly differentiated choroid plexus carcinomas identified at our
      institution contained cells displaying a rhabdoid phenotype. Immunoperoxidase
      stains showed focal positivity for cytokeratin, epithelial membrane antigen,
      glial fibrillary acidic protein, S100, and vimentin. The MIB-1 proliferative
      index ranged from 7.0% to 27.1%. All six tumors were p53 positive. Only the one
      child with Li-Fraumeni syndrome had a p53 germline mutation. Electron microscopy
      verified choroid plexus differentiation and the co-existence of rhabdoid cells.
      Of the five studied, four had deletions of chromosome 22 [three with monosomy 22
      and one with del(22)(q12)]. Thus, there was a phenotypic and genotypic overlap
      between choroid plexus carcinomas and rhabdoid tumors.

PMID- 11826361
TI  - Association of alveolar rhabdomyosarcoma with the Beckwith-Wiedemann syndrome.
AB  - Rhabdomyosarcoma (RMS) is a soft tissue tumor of childhood frequently diagnosed
      between the first and fifth year of life. Children with the Beckwith-Wiedemann
      syndrome (BWS), a congenital overgrowth syndrome characterized by exomphalos,
      macroglossia, and macrosomia, have an increased risk of developing childhood
      tumors including Wilms tumor, hepatoblastoma, neuroblastoma, and RMS. Although an
      association between RMS and the BWS is well accepted, only four cases have been
      reported to date, and of these, three were reported as embryonal RMS. Based on
      these data, an association between BWS and embryonal RMS has been proposed. We
      report three additional cases of BWS with RMS and review the clinical data for
      each patient as well as the pathology of their tumors. All three cases of BWS had
      histology consistent with alveolar RMS and were diagnosed at 6 weeks and 5 and 13
      years of age. In two of these BWS cases, constitutional defects of 11p15
      imprinting were demonstrated. Furthermore, cytogenetic analysis of the tumors did
      not detect the t(2;13) or t(1;13) translocations that generate the PAX3- or PAX7
      FKHR fusion proteins common to alveolar RMS. These observations suggest that the
      development of alveolar RMS tumors in BWS may occur without the chromosomal
      rearrangement producing the PAX-FKHR fusion protein. In summary, we present three
      new cases of RMS demonstrating a new association between BWS and an uncommon
      subtype of alveolar RMS. The absence of the translocations commonly associated
      with alveolar rhabdomyosarcoma suggests a common 11p15 pathway for alveolar RMS
      and BWS.

PMID- 11826362
TI  - Proliferation to paucity: evolution of bile duct abnormalities in a case of
      Alagille syndrome.
AB  - Alagille syndrome is an autosomal dominant disorder characterized by
      abnormalities in multiple organ systems, including the liver, and is caused by
      mutations in JAG1. Chronic cholestasis secondary to paucity of interlobular bile
      ducts is traditionally both a clinical and a pathologic hallmark of this disease
      at diagnosis. We describe the biliary changes on serial liver biopsies in a
      patient who presented with jaundice and extrahepatic stigmata of Alagille
      syndrome. Her initial specimens at 6 and 10 months of age demonstrated
      interlobular bile duct proliferation and cholestasis, suggestive of distal
      biliary obstruction. A specimen at 2 years of age showed near-total absence of
      interlobular bile ducts, with the classic histologic appearance of bile duct
      paucity. We present this case to underscore the potential pitfalls in
      interpreting cholestatic liver morphology in the absence of clinical information.
      The progression of bile duct abnormalities is discussed in the context of the
      role postulated for JAG1 in postnatal liver growth and development.

PMID- 11826363
TI  - Pediatric chordoid glioma with chondroid metaplasia.
AB  - Chordoid gliomas are uncommon primary brain tumors that arise in the region of
      the third ventricle. Reports of this entity to date have been limited to adults.
      We present a case of a chordoid glioma arising in the hypothalamic/third
      ventricle region of a 12-year-old male who presented with visual symptoms. The
      neoplasm consisted of cords and clusters of well-differentiated, spindled-to
      rounded cells containing abundant eosinophilic cytoplasm within a prominent
      mucinous matrix. Unlike other chordoid gliomas, this lesion contained islands and
      sheets showing cartilaginous differentiation intermixed with the glial component.
      A graded transition between neoplastic glial and chondroid regions was evident,
      and cells in both regions were strongly immunoreactive for GFAP and S-100.
      Cartilaginous metaplasia is infrequent in gliomas, but occurs most often in
      pediatric neoplasms of the midline such as this chordoid glioma. Thus, chondroid
      metaplasia represents an unusual histopathologic feature of chordoid glioma-in
      this case, presenting in a child.

PMID- 11826364
TI  - Deletion of the NF2 region in both meningioma and juxtaposed
      meningioangiomatosis: case report supporting a neoplastic relationship.
AB  - We report a case of juxtaposed atypical meningioma and meningioangiomatosis (MA)
      in an 8-year-old boy with no clinical stigmata or family history of
      neurofibromatosis. We studied the proliferative activity and genetic changes in
      the two lesions in an attempt to define their biologic and pathogenetic
      relationships. The MIB-1 index was 11% in the meningioma and <1% in the MA,
      indicating increased proliferative activity in the meningioma. Fluorescence in
      situ hybridization was done for two chromosomal regions commonly deleted in
      meningiomas. There was loss of the neurofibromatosis 2 locus (22q12) in both the
      meningioma and MA. Conversely, the region of 1p32 was not deleted. Our results
      indicate that both the meningioma and MA arose from the same clonal process, with
      the meningioma probably undergoing additional, but undefined, genetic alterations
      that confer upon it a more proliferative potential. This loss of 22q12 in the MA
      raises doubt about the presumed hamartomatous nature of MA.

PMID- 11826365
TI  - Lethal cardiac tachyarrhythmia in a patient with neonatal carnitine-acylcarnitine
      translocase deficiency.
AB  - Carnitine-acylcarnitine translocase (CACT) deficiency is an inherited defect of
      the co-transport of free and esterified carnitine across the inner mitochondrial
      membrane. We report a case of CACT deficiency in a newborn who died at 72 h of
      age from severe, intractable cardiac tachyarrhythmia, despite an improvement in
      his neurological and biochemical status. Postmortem examination showed marked
      steatosis of myocardium, liver, and kidney. In addition, electron microscopic
      studies showed virtually complete elimination of mitochondria from
      cardiomyocytes. It appears that the correction of the acute metabolic
      derangements in this condition may not prevent rapid progression to death,
      suggesting that the rhythm disturbances in CACT deficiency result from prior and
      ongoing accumulation of toxic metabolites, rather than from an acute metabolic
      derangement. Furthermore, we speculate that the choice of anti-arrhythmic agent
      in this patient may paradoxically have contributed to his death.

PMID- 11826366
TI  - Prenatal closure of abdominal defect in gastroschisis: case report and review of
      the literature.
AB  - With the routine use of fetal imaging studies during prenatal care, increased
      numbers of unusual intrauterine events are now detected. Prenatal closure of the
      abdominal defect in gastroschisis is an example. We report a 34 5/7-week
      stillborn who had prenatal closure of a ventral abdominal wall defect, which had
      been seen earlier on fetal ultrasound examination. Two ultrasound examinations
      performed at 15 1/7 weeks and 19 1/7 weeks showed a mass of exteriorized bowel
      that herniated through the abdominal defect, just to the right of the umbilical
      cord. At 30 1/7 weeks, no exteriorized bowel was seen, but thickened and dilated
      intraabdominal bowel was identified. No abdominal defect or exteriorized bowel
      was found at autopsy. There was a severely dilated proximal jejunum with the
      absence of the rest of the small intestine and the right side of the colon. The
      remaining left side of the colon was small and blind proximally. Six similar
      isolated examples have been reported since 1991. Prenatal closure of an abdominal
      defect was associated with long-segment atresia of the midintestine in each case.
      We believe that the spontaneous closure of this abdominal defect was associated
      with atresia and resorption of exteriorized bowel. It is likely some of the cases
      of long-segment atresia may in fact be associated with closed gastroschisis.

PMID- 11826367
TI  - Bloom syndrome in sibs: first reports of hepatocellular carcinoma and Wilms tumor
      with documented anaplasia and nephrogenic rests.
AB  - The triad of small body size, immunodeficiency, and sun-sensitive facial erythema
      characterizes the phenotype Bloom syndrome (BS), a rare autosomal recessive
      disorder with a striking predisposition to multiple types of cancers that arise
      earlier than expected in the general population. Here we report two sibs with BS.
      The older, a 15-year-old-girl, developed a hepatocellular carcinoma, a neoplasm
      not yet reported in association with BS. Her younger brother developed an
      anaplastic Wilms tumor (WT) associated with nephrogenic rests at the age of 31/2
      years, and this was followed by a myelodysplastic syndrome. Complex cytogenetic
      abnormalities were identified in all three neoplasms. These examples expand the
      spectrum of malignancies occurring in BS to include liver cell neoplasms, and
      confirm the association of nephrogenic rests with WT, even in the setting of BS.

PMID- 11826396
TI  - Keratins: guardians of the liver.

PMID- 11826397
TI  - Rationale for trials of long-term mycophenolate mofetil therapy for primary
      biliary cirrhosis.

PMID- 11826398
TI  - Insulin signaling in the transcriptional and posttranscriptional regulation of
      CYP2E1 expression.
AB  - Diabetes has been reported to increase the expression of cytochrome P450 (CYP)
      2E1 messenger RNA (mRNA) and protein several-fold, and enhanced expression has
      been associated with elevated ketone bodies. Primary cultured rat hepatocytes
      were used to explore ketone body and insulin regulation of CYP2E1 expression.
      Hydroxybutyrate and acetoacetate (AC), alone or in combination, either failed to
      affect or decreased CYP2E1 mRNA levels by up to 90% relative to untreated
      hepatocytes. Insulin produced a concentration-dependent decrease in CYP2E1 mRNA
      levels, and insulin receptor immunoprecipitation showed a correspondence between
      receptor phosphorylation and the decrease in CYP2E1 mRNA levels at physiologic
      levels of insulin. Phosphatase inhibitors decreased CYP2E1 mRNA levels by greater
      than 95%. The phosphatidylinositol 3-kinase (PI3-kinase) inhibitors wortmannin or
      LY294002 and rapamycin, an inhibitor of p70 S6 kinase phosphorylation,
      ameliorated the insulin-mediated decrease in CYP2E1 mRNA levels. Geldanamycin,
      which inhibits Src kinase, also abrogated the insulin-mediated decrease in CYP2E1
      mRNA levels. In contrast, the protein kinase C (PKC) inhibitor
      bisindolylmaleimide, the mitogen-activated protein kinase kinase (MEK) inhibitor
      PD98059, and the p38 mitogen-activated protein (MAP) kinase inhibitor SB202190
      did not affect the insulin-mediated decrease in CYP2E1. CYP2E1 mRNA half-life
      decreased from approximately 48 hours in the absence of insulin to approximately
      15 hours at 10 nmol/L insulin, and this decrease was prevented by wortmannin. The
      half-life of CYP2B mRNA was increased by insulin, whereas that of CYP3A was
      unaffected. Analysis of CYP2E1 gene transcription using heterogeneous nuclear RNA
      (hnRNA) showed that insulin suppressed CYP2E1 transcription. In conclusion, these
      data show involvement of transcriptional and posttranscriptional mechanisms in
      the insulin-mediated regulation of CYP2E1 and implicate PI3-kinase, p70 S6
      kinase, and Src kinase in mediating these effects.

PMID- 11826400
TI  - In vivo cell lineage analysis in cyproterone acetate-treated rat liver using
      genetic labeling of hepatocytes.
AB  - Genetic labeling using recombinant retroviruses is a powerful strategy for the
      study of cell lineage in the liver. However, this type of vector is only able to
      infect dividing cells. The synthetic steroid cyproterone acetate (CPA) is
      mitogenic and carcinogenic in the adult rat liver. In this study, we used
      retroviral vectors carrying the nuclear targeted beta-galactosidase gene to
      selectively label and follow the fate of hepatocytes dividing on administration
      of CPA. Labeled cells as well as those in mitosis were preferentially located
      around the portal tract, whereas apoptotic bodies were predominant in the
      pericentral area. Labeled hepatocytes did not disappear after apoptosis,
      suggesting a preferential elimination of nontransduced cells. The presence of
      labeled binucleated hepatocytes showed the persistence of a binucleation process.
      Finally, we performed long-term analysis of labeled cells in transgenic animals
      tolerant for beta-galactosidase and treated with 2-acetylaminofluorene (2-AAF) to
      promote the growth of CPA-initiated hepatocytes. The presence of beta
      galactosidase-positive hepatocyte clones showed that hepatocytes divided during
      treatment with 2-AAF. Only 3% of beta-galactosidase clones were positive for the
      placental form of glutathione S-transferase (GSTp), indicating the absence of a
      preferential appearance of preneoplastic foci in the population of beta
      galactosidase-labeled hepatocytes. In conclusion, our results show that the
      mitogenic and tumor-initiating activities of CPA are directed toward different
      hepatocyte populations.

PMID- 11826399
TI  - S-adenosylmethionine and methylthioadenosine are antiapoptotic in cultured rat
      hepatocytes but proapoptotic in human hepatoma cells.
AB  - S-adenosylmethionine (AdoMet) is an essential compound in cellular
      transmethylation reactions and a precursor of polyamine and glutathione synthesis
      in the liver. In liver injury, the synthesis of AdoMet is impaired and its
      availability limited. AdoMet administration attenuates experimental liver damage,
      improves survival of alcoholic patients with cirrhosis, and prevents experimental
      hepatocarcinogenesis. Apoptosis contributes to different liver injuries, many of
      which are protected by AdoMet. The mechanism of AdoMet's hepatoprotective and
      chemopreventive effects are largely unknown. The effect of AdoMet on okadaic acid
      (OA)-induced apoptosis was evaluated using primary cultures of rat hepatocytes
      and human hepatoma cell lines. AdoMet protected rat hepatocytes from OA-induced
      apoptosis dose dependently. It attenuated mitochondrial cytochrome c release,
      caspase 3 activation, and poly(ADP-ribose) polymerase cleavage. These effects
      were independent from AdoMet-dependent glutathione synthesis, and mimicked by 5'
      methylthioadenosine (MTA), which is derived from AdoMet. Interestingly, AdoMet
      and MTA did not protect HuH7 cells from OA-induced apoptosis; conversely both
      compounds behaved as proapoptotic agents. AdoMet's proapoptotic effect was dose
      dependent and observed also in HepG2 cells. In conclusion, AdoMet exerts opposing
      effects on apoptosis in normal versus transformed hepatocytes that could be
      mediated through its conversion to MTA. These effects may participate in the
      hepatoprotective and chemopreventive properties of this safe and well-tolerated
      drug.

PMID- 11826401
TI  - Protection against acetaminophen-induced liver injury and lethality by
      interleukin 10: role of inducible nitric oxide synthase.
AB  - Mechanistic study of idiosyncratic drug-induced hepatitis (DIH) continues to be a
      challenging problem because of the lack of animal models. The inability to
      produce this type of hepatotoxicity in animals, and its relative rarity in
      humans, may be linked to the production of anti-inflammatory factors that prevent
      drug-protein adducts from causing liver injury by immune and nonimmune
      mechanisms. We tested this hypothesis by using a model of acetaminophen (APAP)
      induced liver injury in mice. After APAP treatment, a significant increase was
      observed in serum levels of interleukin (IL)-4, IL-10, and IL-13, cytokines that
      regulate inflammatory mediator production and cell-mediated autoimmunity. When IL
      10 knockout (KO) mice were treated with APAP, most of these mice died within 24
      to 48 hours from liver injury. This increased susceptibility to APAP-induced
      liver injury appeared to correlate with an elevated expression of liver
      proinflammatory cytokines, tumor necrosis factor (TNF)-alpha, and IL-1, as well
      as inducible nitric oxide synthase (iNOS). In this regard, mice lacking both IL
      10 and iNOS genes were protected from APAP-induced liver injury and lethality
      when compared with IL-10 KO mice. All strains, including wild-type animals,
      generated similar amounts of liver APAP-protein adducts, indicating that the
      increased susceptibility of IL-10 KO mice to APAP hepatotoxicity was not caused
      by an enhanced formation of APAP-protein adducts. In conclusion, these findings
      suggest that an important feature of the normal response to drug-induced liver
      injury may be the increased expression of anti-inflammatory factors such as IL
      10. Certain polymorphisms of these factors may have a role in determining the
      susceptibility of individuals to idiosyncratic DIH.

PMID- 11826402
TI  - Mdr P-glycoproteins are not essential for biliary excretion of the hydrophobic
      heme precursor protoporphyrin in a griseofulvin-induced mouse model of
      erythropoietic protoporphyria.
AB  - Hepatic complications in erythropoietic protoporphyria (EPP) have been attributed
      to toxic actions of accumulated protoporphyrin (PP). PP can only be removed via
      the bile but transport systems involved have not been defined. The aim of this
      study was to gain insight in the mode of biliary PP excretion, with emphasis on
      the potential contribution of the Mdr1 P-glycoprotein export pump and biliary
      lipids as PP carriers. Control mice and mice homozygous for Mdr1a/b (Abcb1) or
      Mdr2 (Abcb4) gene disruption, the latter unable to secrete phospholipids and
      cholesterol into bile, were treated with griseofulvin to chemically induce
      protoporphyria. All groups showed dramatically increased PP levels in
      erythrocytes and liver after griseofulvin treatment. Histologically, massive PP
      deposits were found in livers of control and Mdr1a/b(-/-) mice but not in those
      of Mdr2(-/-) mice. Serum unesterified cholesterol and phospholipids were
      increased by griseofulvin because of formation of lipoprotein-X in control and
      Mdr1a/b(-/-) mice only. Yet, bile flow was not impaired in griseofulvin-treated
      mice, and biliary bile salt, phospholipid, and cholesterol secretion rates were
      significantly increased. Surprisingly, biliary PP excretion was similar in all 3
      groups of griseofulvin-treated mice: the observed linear relationship between
      hepatic and biliary PP concentrations and identical liver-to-bile concentration
      ratios in treated and untreated mice suggest a passive mode of excretion. In
      conclusion, the data show that Mdr P-glycoproteins are not critically involved in
      biliary removal of excess PP and indicate that the presence of biliary lipids is
      required for formation of intrahepatic PP deposits.

PMID- 11826403
TI  - Activation of the Raf-1/MEK/ERK cascade by bile acids occurs via the epidermal
      growth factor receptor in primary rat hepatocytes.
AB  - Bile acids have been reported to activate several different cell signaling
      cascades in rat hepatocytes. However, the mechanism(s) of activation of these
      pathways have not been determined. This study aims to determine which bile acids
      activate the Raf-1/MEK/ERK cascade and the mechanism of activation of this
      pathway. Taurodeoxycholic acid (TDCA) stimulated (+235%) the phosphorylation of
      p(74) Raf-1 in a time (5 to 20 minutes) and concentration-dependent (10 to 100
      micromol/L) manner. Raf-1 and ERK activities were both significantly increased by
      most bile acids tested. Deoxycholic acid (DCA) was the best activator of ERK (3.6
      fold). A dominant negative Ras (N17) construct expressed in primary hepatocytes
      prevented the activation of ERK by DCA. The epidermal growth factor receptor
      (EGFR)-specific inhibitor (AG1478) significantly inhibited (approximately 81%)
      the activation of ERK by DCA. DCA rapidly (30 to 60 seconds) increased
      phosphorylation of the EGFR (approximately 2-fold) and Shc (approximately 4
      fold). A dominant negative mutant of the EGFR (CD533) blocked the ability of DCA
      to activate ERK. In conclusion, these results show that DCA activates the Raf
      1/MEK/ERK signaling cascade in primary hepatocytes primarily via an EGFR/Ras
      dependent mechanism.

PMID- 11826404
TI  - Derivation, characterization, and phenotypic variation of hepatic progenitor cell
      lines isolated from adult rats.
AB  - Liver progenitor cells (LPCs) cloned from adult rat livers following allyl
      alcohol injury express hematopoietic stem cell and early hepatic lineage markers
      when cultured on feeder layers; under these conditions, neither mature hepatocyte
      nor bile duct, Ito, stellate, Kupffer cell, or macrophage markers are detected.
      These phenotypes have remained stable without aneuploidy or morphological
      transformation after more than 100 population doublings. When cultured without
      feeder layers, the early lineage markers disappear, and mature hepatocyte markers
      are expressed; mature hepatocytic differentiation and cell size are also
      augmented by polypeptide and steroidal growth factors. In contrast to hepatocytic
      potential, duct-like structures and biliary epithelial markers are expressed on
      Matrigel. Because they were derived without carcinogens or mutagens, these
      bipotential LPC lines provide novel tools for models of cellular plasticity and
      hepatocarcinogenesis, as well as lines for use in cellular transplantation, gene
      therapy, and bioreactor construction.

PMID- 11826406
TI  - Phosphorylation of retinoid X receptor suppresses its ubiquitination in human
      hepatocellular carcinoma.
AB  - Retinoid X receptor alpha (RXRalpha) has emerged as an important nuclear receptor
      involved in hepatocarcinogenesis, because its ligand suppresses the development
      of hepatocellular carcinoma (HCC) in both experimental and clinical studies. We
      have demonstrated that phosphorylation of RXRalpha at serine 260 interferes with
      its function and delays its degradation in cultured human HCC, leading to
      enhanced cellular proliferation. Here, we show that in normal liver and in
      nonproliferating hepatocyte cultures, RXRalpha is unphosphorylated and highly
      ubiquitinated, rendering it sensitive to proteasome-mediated degradation. On the
      other hand, phosphoserine 260 RXRalpha is resistant to ubiquitination and
      proteasome-mediated degradation in both human HCC tissues and a human HCC cell
      line, HuH7. In these tissues and cells, serine 260 is phosphorylated by mitogen
      activated protein (MAP) kinase. In proliferating normal hepatocytes, similar to
      HCC cells, RXRalpha is also phosphorylated at serine 260 and resistant to
      ubiquitin-mediated degradation by proteasome, but this ubiquitination of RXRalpha
      is differentially regulated between HCC cells and normal hepatocytes. In
      proliferating hepatocytes, 9-cis retinoic acid (9cRA), a ligand to RXRalpha,
      suppresses MAP kinase-mediated phosphorylation and thereby enhances
      ubiquitination of RXRalpha, whereas it fails to exert these effects in HCC cells.
      In conclusion, switching of the ubiquitin/proteasome-dependent degradation of
      RXRalpha by phosphorylation at serine 260 may be responsible for the aberrant
      growth of HCC and its suppression by retinoids.

PMID- 11826405
TI  - Inhibition of rat liver fibrogenesis through noradrenergic antagonism.
AB  - The effect of adrenergic innervation and/or circulating catecholamines on the
      function of liver fibrogenic cells is poorly understood. Our aim was to
      investigate the effects of noradrenergic antagonism on carbon tetrachloride
      (CCl4)-induced liver fibrosis in rats. Two weeks of CCl4 induced an approximately
      5-fold increase in the area of fibrosis as compared with controls. The addition
      of 6-hydroxydopamine (OHDA), a toxin that destroys noradrenergic fibers,
      decreased fibrosis by 60%. After 6 weeks of CCl4, the area of fibrosis increased
      about 30-fold in CCl4-treated animals and was decreased by 36% with OHDA. At 2
      weeks, OHDA abrogated the CCl4-induced increase in mRNA level of tissue inhibitor
      of matrix metalloproteinases-1 (TIMP-1), an inhibitor of extracellular matrix
      degradation, and it greatly reduced it at 6 weeks. Finally, when rats treated
      with CCl4 for 2 weeks also received prazosin, an antagonist of alpha1-adrenergic
      receptors, fibrosis was decreased by 83%. In conclusion, destruction of
      noradrenergic fibers or antagonism of noradrenergic signaling through alpha1
      receptors inhibited the development of liver fibrosis. Because adrenoreceptor
      antagonists have a very sound safety profile, they appear as attractive drugs to
      reduce liver fibrogenesis.

PMID- 11826407
TI  - Absence of nuclear factor kappaB inhibition by NSAIDs in hepatocytes.
AB  - Stimulation of fetal hepatocytes with proinflammatory cytokines and
      lipopolysaccharide promotes the expression of cyclooxygenase-2 (COX-2) and nitric
      oxide synthase-2 (NOS-2), whereas the hepatoma cell line HepG2 exhibits a
      behavior similar to that described for adult hepatocytes and only expresses NOS
      2. The effect of nonsteroidal anti-inflammatory drugs (NSAIDs) on the
      inflammatory onset was analyzed in these cells since in addition to the
      inhibition of cyclooxygenase activity, these drugs interfere with other signaling
      pathways related with the inflammatory response. Inhibition of nuclear factor
      kappaB (NF-kappaB) activation by aspirin and salicylate has been described in
      many cells. However, incubation of hepatic cells with salicylate, aspirin,
      indomethacin, ibuprofen, or 5,5-dimethyl-3(3-fluorophenyl)-4-(4
      methylsulfonyl)phenyl-2(5H)-furanone (DFU), a fluorinated derivative of
      rofecoxib, failed to impair IkappaB kinase activity, the processing of NF-kappaB,
      and the expression of NF-kappaB-dependent genes, such as NOS-2. Moreover,
      selective COX-2 inhibitors did not promote apoptosis in hepatocytes under
      inflammatory conditions, suggesting that prostaglandins are not required to
      maintain cell viability. In conclusion, these data indicate that hepatocytes are
      not sensitive to NF-kappaB inhibition by NSAIDs and that these drugs, especially
      the COX-2 selective inhibitors, do not alter cell viability.

PMID- 11826408
TI  - Response to steroids in de novo autoimmune hepatitis after liver transplantation.
AB  - Graft dysfunction associated with autoimmune phenomena has been recently
      described in liver transplant recipients without previous autoimmune disease.
      However, the natural history, diagnostic criteria, and definitive therapeutic
      approach of de novo autoimmune hepatitis (de novo AIH) are poorly understood. We
      report 12 cases of de novo AIH 27.9 +/- 24.5 months after liver transplantation:
      the outcome of 7 patients treated with steroids is compared with a group of 5
      nontreated patients. Nontreated patients lost the graft after 5.8 +/- 2.6 months
      from de novo AIH onset. All treated patients were alive after 48.4 +/- 14 (29-65)
      months from de novo AIH onset, and none of them lost the graft. However, 5
      patients relapsed in relation to steroid tapering. All patients presented an
      atypical antiliver/kidney cytosolic autoantibody, associated to classical
      autoantibodies in 10 cases. Histological study showed several degrees of lobular
      necrosis and inflammatory infiltrate. HLA antigen frequencies and matching were
      compared with 2 control groups (16 orthotopic liver transplantation [LTX]
      patients without de novo AIH and 929 healthy blood donors); de novo AIH patients
      showed a higher prevalence of HLA-DR3 (54.5% vs. 25.9%, P =.04) than healthy
      controls, which was not observed in LTX patients without de novo AIH. In
      conclusion, this new disease should be included in the differential diagnosis of
      unexplained graft dysfunction. In addition, treatment with steroids results in a
      dramatically improved outcome. However, maintenance therapy is usually required.

PMID- 11826409
TI  - Critical flicker frequency for quantification of low-grade hepatic
      encephalopathy.
AB  - Subclinical hepatic encephalopathy (SHE) is currently diagnosed by psychometric
      tests or neurophysiologic techniques. In view of its sociomedical relevance,
      simple and reproducible tests for routine diagnosis are required. This study
      evaluates critical flicker-frequency thresholds for quantification of low-grade
      hepatic encephalopathy. A total of 115 patients (92 with cirrhosis, 23 controls)
      were analyzed for HE severity (mental state, computerized psychometric tests),
      and the threshold frequencies at which light pulses are perceived as fused
      (fusion frequency) or flickering light (critical flicker frequency [CFF]). CFF
      was a highly reproducible parameter with little age, day-time, and training
      dependency. CFFs in cirrhotic patients without HE (HE 0) were not different from
      those found in noncirrhotic controls. Significantly lower CFFs were found in
      cirrhotic patients with subclinical or manifest HE, and the various HE groups
      separated from each other at a high level of significance (P <.01). By using a
      CFF cut-off value of 39 Hz, a 100% separation of patients with manifest HE from
      noncirrhotic controls and HE 0 cirrhotic patients was obtained. SHE patients
      separated from HE 0 cirrhotic patients with high sensitivity (55%) and
      specificity (100%). The HE severity-dependent differences were found in both,
      alcoholic and posthepatitic cirrhosis. Statistically significant correlations (P
      <.01) were found between CFFs and individual psychometric tests. Aggravation of
      preexisting HE after transjugular intrahepatic portosystemic stent shunt (TIPS)
      implantation was accompanied by a corresponding decrease of CFF, whereas
      improvement of HE increased CFF. In conclusion, CFF is a sensitive, simple, and
      reliable parameter for quantification of low-grade HE severity in cirrhotic
      patients and may be useful for the detection and monitoring of SHE.

PMID- 11826410
TI  - Nonalcoholic steatohepatitis, insulin resistance, and metabolic syndrome: further
      evidence for an etiologic association.
AB  - This study aims to determine the presence of the components of the metabolic
      syndrome in primary nonalcoholic steatohepatitis (NASH) and to assess the role of
      liver disease in the genesis of peripheral hyperinsulinemia. Nineteen patients
      (18 men and 1 woman; mean age, +/- SD, 38 +/- 10 years; body mass index [BMI], 26
      +/- 2 kg/m(2)) with histologic evidence of NASH were enrolled; 19 age- and sex
      matched normal subjects were investigated as controls. Plasma glucose, insulin,
      and C-peptide levels were measured during an oral glucose tolerance test, and a
      frequently sampled intravenous glucose tolerance test (FSIGT), analyzed by
      minimal modeling technique, was performed. Compared with controls, the NASH group
      had lower insulin sensitivity (3.84 +/- 2.44 vs. 7.48 +/- 3.01 10(-4) x min(
      1)/microU/mL; P =.0003) and higher total insulin secretion (21 +/- 13 vs. 10 +/-
      3 nmol/L in 240 minutes; P =.001). Hepatic insulin extraction was similar in both
      groups (69.8% +/- 16.1% vs. 70.2% +/- 18.3%; P =.854). According to the results
      of the oral glucose tolerance test, no patient was classified as diabetic, 5 were
      classified as glucose intolerant, and 1 was classified as having impaired fasting
      glycemia. Nine patients (47%) had at least the 2 minimum criteria required to
      define the metabolic syndrome according to the European Group for the Study of
      Insulin Resistance (EGIR). In conclusion, hyperinsulinemia and insulin resistance
      occur frequently in patients with NASH; these conditions do not stem from a
      reduced hepatic insulin extraction but from an enhanced pancreatic insulin
      secretion compensatory to reduced insulin sensitivity. The derangement of insulin
      regulation, often associated with the metabolic syndrome, may play a causal role
      in the pathogenesis of NASH.

PMID- 11826411
TI  - NASH and insulin resistance: Insulin hypersecretion and specific association with
      the insulin resistance syndrome.
AB  - Nonalcoholic steatohepatitis (NASH) is often linked with disorders that are
      clearly associated with insulin resistance (IR): obesity, type 2 diabetes
      mellitus, and hypertriglyceridemia. We tested the hypotheses that (1) IR is an
      essential requirement for the development of NASH and (2) a high association
      between IR and liver disease is relatively specific for NASH. We measured body
      mass index (BMI), waist/hip ratio, and fasting serum lipid, insulin, C-peptide,
      and glucose levels in 66 patients with NASH (21 with advanced fibrosis and 45
      with mild fibrosis). IR was determined by the homeostasis model assessment
      (HOMA). We also determined the strength of the association of NASH with insulin
      resistance syndrome (IRS) as defined by World Health Organization criteria. To
      assess whether the finding of IR was relatively specific to NASH rather than
      simply to obesity or liver disease, we compared the results of a subset of 36
      patients with less-severe NASH with 36 age- and sex-matched patients with chronic
      hepatitis C virus (HCV) of comparable fibrotic severity. IR was confirmed in 65
      patients (98%) with NASH, and 55 (87%) fulfilled minimum criteria for IRS. IR was
      found in lean as well as in overweight and obese patients. The IR values and the
      prevalence of IRS (75% vs. 8.3%) were significantly higher in those with NASH
      than in comparable cases of HCV. Hyperinsulinemia was attributable to increased
      insulin secretion rather than decreased hepatic extraction. In conclusion, most
      patients with NASH have IRS, and there is a near-universal association between
      NASH and IR irrespective of obesity. IR is present in mild as well as advanced
      cases of NASH but is unusual in chronic HCV of similar fibrotic severity.

PMID- 11826413
TI  - TIPS versus drug therapy in preventing variceal rebleeding in advanced cirrhosis:
      a randomized controlled trial.
AB  - Prevention of variceal rebleeding is mandatory in cirrhotic patients. We compared
      the efficacy, safety, and cost of transjugular intrahepatic portosystemic shunt
      (TIPS) versus pharmacologic therapy in preventing variceal rebleeding in patients
      with advanced cirrhosis. A total of 91 Child-Pugh class B/C cirrhotic patients
      surviving their first episode of variceal bleeding were randomized to receive
      TIPS (n = 47) or drug therapy (propranolol + isosorbide-5-mononitrate) (n = 44)
      to prevent variceal rebleeding. Mean follow-up was 15 months. Rebleeding occurred
      in 6 (13%) TIPS-treated patients versus 17 (39%) drug-treated patients (P =.007).
      The 2-year rebleeding probability was 13% versus 49% (P =.01). A similar number
      of reinterventions were required in the 2 groups; these were mainly angioplasty
      +/- restenting in the TIPS group (90 of 98) and endoscopic therapy for rebleeding
      in the medical group (45 of 62) (not significant). Encephalopathy was more
      frequent in TIPS than in drug-treated patients (38% vs. 14%, P =.007). Child-Pugh
      class improved more frequently in drug-treated than in TIPS-treated patients (72%
      vs. 45%; P =.04). The 2-year survival probability was identical (72%). The
      identified cost of therapy was double for TIPS-treated patients. In summary,
      medical therapy was less effective than TIPS in preventing rebleeding. However,
      it caused less encephalopathy, identical survival, and more frequent improvement
      in Child-Pugh class with lower costs than TIPS in high-risk cirrhotic patients.
      This suggests that TIPS should not be used as a first-line treatment, but as a
      rescue for failures of medical/endoscopic treatments (first-option therapies).

PMID- 11826412
TI  - Effect of liver transplantation on inflammatory bowel disease in patients with
      primary sclerosing cholangitis.
AB  - This report investigates the influence of liver transplantation and concomitant
      immunosuppression on the course of progression of inflammatory bowel disease
      (IBD) and discusses statistical methodology appropriate for such settings. The
      data on 303 patients who underwent liver transplantation for primary sclerosing
      cholangitis (PSC) were analyzed using person-time analysis and Cox regression,
      with the duration of IBD as the time variable and transplantation as a segmented
      time-dependent covariate, to take into account both posttransplant and
      pretransplant history of IBD. The need for colectomy and appearance of colorectal
      cancer were taken as outcome measures. The only significant risk factor in the
      multivariate model for colectomy was transplantation itself, which increased the
      risk of colectomy due to intractable disease (Wald statistic; P =.001). None of
      the variables available for analysis were found to influence the risk of colon
      cancer significantly. Graphs showing the dependence of the instantaneous risk of
      cancer on the time from onset of IBD and its independence from the latter in the
      case of colectomy are presented. The use of a unique statistical methodology
      described for the first time in this setting led us to the somewhat surprising
      conclusion that transplantation and concomitant use of immunosuppression
      accelerate the progression of IBD. At the same time, transplantation does not
      affect the incidence of colorectal cancer. These results confirm the findings of
      some recent studies and can potentially shed new light on the disease
      pathogenesis.

PMID- 11826414
TI  - Activation of eNOS in rat portal hypertensive gastric mucosa is mediated by TNF
      alpha via the PI 3-kinase-Akt signaling pathway.
AB  - Activation of endothelial nitric oxide synthase (eNOS) in portal hypertensive
      (PHT) gastric mucosa leads to hyperdynamic circulation and increased
      susceptibility to injury. However, the signaling mechanisms for eNOS activation
      in PHT gastric mucosa and the role of TNF-alpha in this signaling remain unknown.
      In PHT gastric mucosa we studied (1) eNOS phosphorylation (at serine 1177)
      required for its activation; (2) association of the phosphatidylinositol 3-kinase
      (PI 3-kinase), and its downstream effector Akt, with eNOS; and, (3) whether TNF
      alpha neutralization affects eNOS phosphorylation and PI 3-kinase-Akt activation.
      To determine human relevance, we used human microvascular endothelial cells to
      examine directly whether TNF-alpha stimulates eNOS phosphorylation via PI 3
      kinase. PHT gastric mucosa has significantly increased (1) eNOS phosphorylation
      at serine 1177 by 90% (P <.01); (2) membrane translocation (P <.05) and
      phosphorylation (P <.05) of p85 (regulatory subunit of PI 3-kinase) by 61% and
      85%, respectively; (3) phosphorylation (P <.01) and activity (P <.01) of Akt by
      40% and 52%, respectively; and (4) binding of Akt to eNOS by as much as 410% (P
      <.001). Neutralizing anti-TNF-alpha antibody significantly reduced p85
      phosphorylation, phosphorylation and activity of Akt, and eNOS phosphorylation in
      PHT gastric mucosa to normal levels. Furthermore, TNF-alpha stimulated eNOS
      phosphorylation in human microvascular endothelial cells. In conclusion, these
      findings show that in PHT gastric mucosa, TNF-alpha stimulates eNOS
      phosphorylation at serine 1177 (required for its activation) via the PI 3-kinase
      Akt signal transduction pathway.

PMID- 11826415
TI  - Fine specificity of autoantibodies to soluble liver antigen and liver/pancreas.
AB  - Autoantibodies to soluble liver antigen and liver pancreas (SLA/LP) have been
      described as specific markers for Autoimmune Hepatitis (AIH), occurring in about
      20% of patients with AIH. The high degree of specificity for SLA/LP in autoimmune
      liver disease suggests a possible role in its pathogenesis. This study aims to
      map the exact epitope(s) recognized by SLA/LP autoantibodies and to assess the
      role of molecular mimicry between microbial antigens and self-epitopes. Using
      SLA/LP-reactive sera of 18 individual AIH patients and a pool of 15 patient sera,
      we found the dominant immune reactivity directed to peptide p395-414 and a less
      prominent immune response to 2 other epitopes adjacent to the dominant epitope.
      Immunodominance of peptide p395-414 was confirmed by absorption experiments. The
      SLA/LP autoantibodies of all tested AIH patients were mainly of the IgG1 type,
      suggesting that SLA/LP autoantibodies may arise by a common and specific
      underlying immune stimulus. Based on sequence homologies of the SLA/LP antigenic
      region with viral proteins, it was hypothesized that molecular mimicry may drive
      autoimmunity to SLA/LP. However, the homologous virus-derived peptides were not
      recognized by SLA/LP autoantibodies. Similarly, the only known procaryotic
      homologue, MJ0610 of Methanococcus jannaschii, was only weakly recognized by
      SLA/LP-positive sera. Thus, no evidence could be found for molecular mimicry
      being the causative mechanism for the development of SLA/LP autoantibodies. In
      conclusion, the exquisite epitope specificity and IgG subtype are evidence for
      the maturity of the SLA/LP autoantibody response; a specific autoantigen-driven
      process underlying the immunopathogenesis is likely.

PMID- 11826416
TI  - Primary biliary cirrhosis with additional features of autoimmune hepatitis:
      response to therapy with ursodeoxycholic acid.
AB  - Patients with primary biliary cirrhosis (PBC) may have additional features of
      autoimmune hepatitis (AIH). Corticosteroids usually contraindicated in PBC have
      been advocated for these patients. Patients with antimitochondrial antibody (AMA)
      positive PBC from two previous randomized, controlled trials were assessed for
      features of AIH. Their biochemical, immunologic, and histologic responses to
      ursodeoxycholic acid (UDCA) versus placebo were compared with those without AIH
      features. The survival of patients testing positive or negative for antinuclear
      antibodies (ANA) was also examined. Features of AIH were defined by the presence
      of 2 or more of the following: 1) alanine transaminase (ALT) > 5 x the upper
      limit of normal (ULN); 2) immunoglobulin G (IgG) > 2 x ULN or positive anti
      smooth muscle antibody (ASMA); and 3) moderate to severe lobular inflammation on
      pretreatment liver biopsy. Testing for AMA, ASMA, and ANA was done by
      immunofluorescence. The change in serum bilirubin, alkaline phosphatase (ALP),
      transaminases, IgM, and IgG from baseline to 2 years was compared. Of the 331
      patients randomized, 16 (4.8%) had features of AIH (12 UDCA, 4 placebo). The
      median percent change in serum biochemistry and immunoglobulin values were
      similar in patients with PBC +/- features of AIH after 2 years of therapy with
      UDCA. Over 2 years, little change in histologic features of AIH was observed.
      Survival was similar for patients with PBC with and without ANA. In conclusion,
      features of AIH in PBC may be transient and response to UDCA therapy similar to
      patients with PBC without features of AIH.

PMID- 11826417
TI  - Histologic scoring of liver biopsy in focal nodular hyperplasia with atypical
      presentation.
AB  - The contribution of radio-guided transcutaneous biopsy in the diagnosis of focal
      nodular hyperplasia (FNH) of the liver was compared with the findings on surgical
      specimens to assess its contribution in clinical and radiologic atypical cases.
      This retrospective study involved 30 patients with atypical tumors on imaging who
      underwent liver biopsy and then surgery. All surgical specimens were diagnosed as
      FNH, either classical (n = 18) or nonclassical (n = 12). Imaging data were
      reviewed according to 4 radiologic criteria on magnetic resonance imaging (MRI)
      and/or computed tomography (CT) scan (hypervascularity, homogeneity,
      nonencapsulation, and presence of a central scar), and classified depending on
      the number of criteria found (group I, 4 of 4; group II, 3 of 4; group III, 2 or
      fewer). Histologic assessment of ultrasound (US)-guided liver biopsy recorded
      major diagnostic features (fibrous bands, thick-walled vessels, reactive
      ductules, and nodularity) and minor features (sinusoidal dilatation and
      perisinusoidal fibrosis). "Definite FNH" (3 or 4 major features) was diagnosed in
      14 biopsies, "possible FNH" (2 major and 1 or 2 minor features) in 7 cases, and
      "negative for FNH" (2 or fewer major features without minor features) in 9 cases.
      The diagnosis of FNH on biopsy was reached in 14 cases (58.3%) in patients with 2
      or fewer imaging criteria (group III; n = 24). Biopsies with a diagnosis of
      "possible FNH" corresponded to a large proportion of telangiectatic-type FNH on
      the specimen. In conclusion, liver biopsy does not appear to be necessary in
      cases in which imaging is typical. However, the absence of radiologic diagnostic
      criteria in FNH does not preclude a positive diagnosis on liver needle biopsy.
      Using the proposed histologic scoring system, surgical management may be avoided
      in these cases.

PMID- 11826418
TI  - Adenosine triphosphate infusion increases liver energy status in advanced lung
      cancer patients: an in vivo 31P magnetic resonance spectroscopy study.
AB  - We recently observed inhibition of weight loss in patients with advanced nonsmall
      cell lung cancer after intravenous infusion of ATP. Because liver ATP levels were
      found to be decreased in lung cancer patients with weight loss, the present 31P
      magnetic resonance spectroscopy (MRS) study was aimed at investigating whether
      ATP infusion restores liver energy status in these patients. Nine patients with
      advanced nonsmall-cell lung cancer (stage IIIB/IV) were studied 1 week before
      (baseline) and at 22 to 24 hours of continuous ATP infusion (37-75
      microg/kg/min). Localized hepatic 31P MR spectra (repetition time 15 seconds),
      obtained in the overnight-fasted state, were analyzed for ATP and P(i) content.
      Ten healthy subjects (without ATP infusion) served as control. Liver ATP levels
      in lung cancer patients increased from 8.8 +/- 0.7% (relative to total MR
      detectable phosphate; mean +/- SE) at baseline to 12.2 +/- 0.9% during ATP
      infusion (P <.05), i.e., a level similar to that in healthy subjects (11.9 +/-
      0.9%). The increase in ATP level during ATP infusion was most prominent in
      patients with > or = 5% weight loss (baseline: 7.9 +/- 0.7%, during ATP infusion:
      12.8 +/- 1.0%, P < 0.01). In conclusion, ATP infusion restores hepatic energy
      levels in patients with advanced lung cancer, especially in weight-losing
      patients. These changes may contribute to the previously reported beneficial
      effects of ATP infusion on the nutritional status of lung cancer patients.

PMID- 11826420
TI  - Hepatitis C and cognitive impairment in a cohort of patients with mild liver
      disease.
AB  - Patients with chronic hepatitis C virus (HCV) infection frequently report
      fatigue, lassitude, depression, and a perceived inability to function
      effectively. Several studies have shown that patients exhibit low quality-of-life
      scores that are independent of disease severity. We therefore considered whether
      HCV infection has a direct effect on the central nervous system, resulting in
      cognitive and cerebral metabolite abnormalities. Twenty-seven viremic patients
      with biopsy-proven mild hepatitis due to HCV and 16 patients with cleared HCV
      were tested with a computer-based cognitive assessment battery and also completed
      depression, fatigue, and quality-of-life questionnaires. The HCV-infected
      patients were impaired on more cognitive tasks than the HCV-cleared group (mean
      [SD]: HCV-infected, 2.15 [1.56]; HCV-cleared, 1.06 [1.24]; P =.02). A factor
      analysis showed impairments in power of concentration and speed of working
      memory, independent of a history of intravenous drug usage (IVDU), depression,
      fatigue, or symptom severity. A subgroup of 17 HCV-infected patients also
      underwent cerebral proton magnetic resonance spectroscopy (1H MRS). The
      choline/creatine ratio was elevated in the basal ganglia and white matter in this
      group. Patients who were impaired on 2 or more tasks in the battery had a higher
      mean choline/creatine ratio compared with the unimpaired patients. In conclusion,
      these preliminary results demonstrate cognitive impairment that is unaccounted
      for by depression, fatigue, or a history of IVDU in patients with histologically
      mild HCV infection. The findings on MRS suggest that a biological cause underlies
      this abnormality.

PMID- 11826421
TI  - Neuropsychological impairment in patients with chronic hepatitis C.
AB  - Hepatitis C is the most common cause of chronic liver disease in the United
      States and it significantly reduces quality of life. The role of cognitive
      deficits contributing to the morbidity of this disease has not been well
      characterized. The purpose of this study was to examine cognitive functioning in
      patients with chronic hepatitis C and to investigate relationships among
      parameters of disease severity and performance on neuropsychological tests. Sixty
      six patients with chronic hepatitis C and 14 patients with other chronic liver
      diseases were administered a brief battery of neuropsychological tests assessing
      attention, visuoconstructional ability, learning, memory, and psychomotor speed.
      Cognitive impairment in patients with chronic hepatitis C ranged from 0% on a
      visuoconstructional task to 82% on a measure of sustained attention and
      concentration. Test scores of patients with chronic hepatitis C did not differ
      from those of patients with other chronic liver diseases. Hence, patients with
      and without chronic hepatitis C experience cognitive deficits, especially in
      tasks requiring attention and psychomotor speed. In addition, there was a
      significant relationship between fibrosis stage and test performance, with
      greater fibrosis associated with poorer performance. However, both patients with
      and without cirrhosis exhibited cognitive dysfunction. In conclusion, these
      findings suggest that progressive hepatic injury may result in cognitive problems
      even before the development of cirrhosis. Future studies need to determine the
      effect of this decrease in cognitive function on quality of life.

PMID- 11826419
TI  - Expression of interferon alfa signaling components in human alcoholic liver
      disease.
AB  - Interferon alfa (IFN-alpha) is currently the only well-established therapy for
      viral hepatitis. However, its effectiveness is much reduced (<10%) in alcoholic
      patients. The mechanism underlying this resistance is not fully understood. In
      this study, we examined the expression of IFN-alpha signaling components and its
      inhibitory factors in 9 alcoholic liver disease (ALD) and 8 healthy control liver
      tissues. In comparison with normal control livers, expression of IFN-beta, IFN
      alpha receptor 1/2, Jak1, and Tyk2 remained unchanged in ALD livers, whereas
      expression of IFN-alpha, signal transducer and activator of transcription factor
      1 (STAT1), and p48 were up-regulated and expression of STAT2 was down-regulated.
      Expression of antiviral MxA a karyophilic 75 kd protein induced by IFN in mouse
      cells carrying the influenza virus resistance allele Mx(+) and 2'-5'
      oligoadenylate synthetase (OAS) proteins was not regulated, whereas expression of
      double-stranded RNA-activated protein kinase (PKR) was decreased by 55% in ALD
      livers. Three families of inhibitory factors for the JAK-STAT signaling pathway
      were examined in ALD livers. Members of the suppressor of cytokine signaling
      (SOCS) family, including SOCS 1, 2, 3, and CIS, and the protein tyrosine
      phosphatases, including Shp-1, Shp-2, and CD45, were not up-regulated in ALD
      livers, whereas the phosphorylation of and protein levels of p42/44 mitogen
      activated protein kinase (p42/44MAP kinase) were increased about 3.9- and 3.2
      fold in ALD livers in comparison with normal control livers, respectively. In
      conclusion, these findings suggest that chronic alcohol consumption down
      regulates STAT2 and PKR, but up-regulates p42/44 mitogen-activated protein kinase
      (p42/44MAP kinase), which may cause down-regulation of IFN-alpha signaling in the
      liver of ALD patients.

PMID- 11826422
TI  - Interferon and amantadine in naive chronic hepatitis C: a double-blind,
      randomized, placebo-controlled trial.
AB  - Recent controlled trials on the efficacy of an amantadine/interferon combination
      in treatment-naive patients with chronic hepatitis C yielded contradictory
      results. We therefore conducted a large, double-blind, placebo-controlled,
      multicenter trial in naive patients with chronic hepatitis C: 246 patients were
      randomized to receive interferon alfa-2a (6 MIU sc thrice weekly for 20 weeks,
      then 3 MIU sc thrice weekly) and either amantadine sulphate (2 x 100 mg p.o. QD)
      or placebo. Treatment continued for a total of 52 weeks, if HCV-RNA in serum
      polymerase chain reaction (PCR) had fallen below detection limit (1,000
      copies/mL) at treatment week 10, and stopped otherwise. All patients were
      followed for 24 weeks off therapy. After 10 weeks of treatment, 66/121 patients
      treated with amantadine (55%) and 78/125 treated with placebo (62%) had lost HCV
      RNA (n.s.). After 24 weeks of follow-up, 25 patients in the amantadine (21%) and
      17 (14%) in the placebo group remained HCV-RNA negative (n.s.). During therapy,
      virologic breakthroughs occurred less often in the amantadine than in the placebo
      group [14 (12%) vs. 27 (22%) patients; P =.04]. Multivariate logistic regression
      analysis revealed genotype, viremia level, age, and amantadine therapy [risk
      ratio 0.4 (95%CI 0.2-1.0), P =.05] as predictors of sustained virologic response.
      Adverse events and impact of therapy on quality of life were similar in
      amantadine and placebo treated patients. Compared with current standard treatment
      (interferon/ribavirin), the interferon/amantadine combination was not cost
      effective. In conclusion, amantadine does not add to a clinically relevant extent
      to the treatment of naive patients with chronic hepatitis C.

PMID- 11826423
TI  - Variants of two major T cell epitopes within the hepatitis B surface antigen are
      not recognized by specific T helper cells of vaccinated individuals.
AB  - Several naturally occurring variants of immunogenic T cell epitopes were
      identified within the hepatitis B surface antigen (HBsAg). The effect of these
      variants on the cellular immune response was studied in individuals vaccinated
      against HBV. Class-II restricted T-cell responses of 30 vaccinees were analyzed
      after stimulation of peripheral blood mononuclear cells (PBMCs) with 4 synthetic
      peptides representing the 4 T-cell epitopes of HBsAg known as of yet. The 2
      epitopes P1 (aa 16-33) and P4 (aa 213-226) could be identified as the dominant
      ones in our vaccinees by proliferation assays and enzyme-linked immunospot
      assays. Responses to these epitopes were compared with responses to their
      naturally occurring variants found in HBV isolates of chronic virus carriers.
      Three of 11 variants of epitope P4 led to a complete loss of T-cell reactivity in
      4 of 10 donors, all of whom reacted well to the corresponding wild-type sequence.
      The remaining 6 donors recognized these variants as well as the vaccine epitope.
      Similarly, 3 P1-variants of the 12 found induced only a significantly reduced
      reactivity in 4 of 10 donors, whereas they led to a normal response in the other
      6 individuals. Stimulation of T cells also induced the secretion of antibody to
      HBsAg (anti-HBs) by specific B cells; however, those peptides that failed to
      activate T cells were also unable to cause any significant anti-HBs production.
      In conclusion, our results suggest an immune escape of certain mutant strains of
      HBV in vaccinated individuals could exist at the T-cell level.

PMID- 11826424
TI  - Complex HBV populations with mutations in core promoter, C gene, and pre-S region
      are associated with development of cirrhosis in long-term renal transplant
      recipients.
AB  - Long-term immunosuppressed renal transplant recipients with chronic hepatitis B
      virus (HBV) infection often develop liver cirrhosis (LC) and end-stage liver
      disease (ESLD). This study investigated accumulation and persistence of specific
      HBV mutants in relation to the clinical course in these patients (n = 38; mean
      follow-up, 3.5 years). HBV was analyzed longitudinally via length polymorphism of
      polymerase chain reaction (PCR) fragments (median, 6.5 serum samples per patient)
      as well as by cloning and partial sequencing of 346 full-length HBV genomes.
      Fourteen patients (group 1) developed LC or died from ESLD, whereas 24 patients
      (group 2) showed no evidence of LC during follow-up. Development of LC and ESLD
      was associated with persistence of HBV mutant populations characterized by
      deletions/insertions in core promoter plus deletions in the C gene and/or
      deletions in the pre-S region (86% of group 1 vs. 17% of group 2; P <.0001). HBV
      without these mutations or with core promoter mutations alone were predominantly
      found in group 2 (14% of group 1 vs. 75% of group 2). In patients infected with
      core promoter mutants, the additional appearance and persistence of deletions in
      the C gene and/or the pre-S region were accompanied or followed by development of
      LC and ESLD. The mutations were distributed on individual genomes in various
      combinations, leading to a high complexity of the virus population. In
      conclusion, these data suggest that accumulation and persistence of specific HBV
      populations characterized by mutations in 3 subgenomic regions play a role in
      pathogenesis of LC and ESLD in long-term renal transplant recipients.

PMID- 11826425
TI  - The paradox of nitric oxide in cirrhosis and portal hypertension: too much, not
      enough.

PMID- 11826426
TI  - Treatment of hepatorenal syndrome: lessons from the MARS trial.

PMID- 11826427
TI  - Minimal hepatic encephalopathy: a permanent source of discussion.

PMID- 11826428
TI  - NASH: from liver diseases to metabolic disorders and back to clinical hepatology.

PMID- 11826429
TI  - Sample size in trials of hepatitis C.

PMID- 11826431
TI  - Mitochondrial toxicity in HIV-HCV coinfection: It depends on the choice of
      antiretroviral drugs?

PMID- 11826432
TI  - Endoscopic screening for esophageal varices in cirrhotic patients.

PMID- 11826433
TI  - Ito becomes a star.

PMID- 11826434
TI  - Negotiating HIV-related ethical dilemmas.

PMID- 11826436
TI  - The power of persuasion.

PMID- 11826437
TI  - A practical guide for AIDS agencies.

PMID- 11826435
TI  - A snapshot of HIV for mental health providers.

PMID- 11826438
TI  - Prevention literature review.

PMID- 11826439
TI  - Learning to live while dying.

PMID- 11826440
TI  - HIV resistance: data and spin.

PMID- 11826441
TI  - AIDS treatment news denialist series.

PMID- 11826442
TI  - Buyers' Club List, December 2001.

PMID- 11826443
TI  - Surround yourself with love.

PMID- 11826444
TI  - CDC issues new pregnancy testing recommendations.

PMID- 11826445
TI  - Greetings from a sister in Zimbabwe.

PMID- 11826446
TI  - Making lemonade.

PMID- 11826447
TI  - Keeping hope alive.

PMID- 11826448
TI  - Arm and arm around the world.

PMID- 11826449
TI  - The National Community of Women Living with HIV/AIDS in Uganda (NACWOLA).

PMID- 11826450
TI  - Preserving memories for our children.

PMID- 11826451
TI  - Sexual assault in adults.
AB  - Sexual assault, including rape, is common and is associated with serious
      consequences, including physical and psychological harm, infection and unwanted
      pregnancy. What can healthcare professionals do to help people following such
      attacks?

PMID- 11826452
TI  - Managing peripheral arterial disease in primary care.
AB  - In the UK, around 5% of people aged 55-74 years have intermittent leg pain on
      walking (claudication), a characteristic feature of peripheral arterial disease.
      The fact that their disease is symptomatic puts such individuals at high risk of
      experiencing serious cardiovascular complications. Yet many of them do not
      receive adequate secondary prevention advice and therapy. Here, we review the
      management of peripheral arterial disease in primary care, concentrating on those
      with clinically overt disease.

PMID- 11826453
TI  - [Interrupted pregnancy, mifepristone and patient rights].

PMID- 11826454
TI  - [Dangerous bacterial conditions].

PMID- 11826455
TI  - [A new strategy for prevention of cervical cancer approaching?].

PMID- 11826456
TI  - [Treatment of renal artery stenosis].
AB  - BACKGROUND: Treatment of renal artery stenosis with angioplasty may be performed
      in patients with renovascular hypertension, ischaemic renal failure, or to
      preserve renal function. MATERIAL AND METHODS: From 1982 to 1993 Rikshospitalet
      performed 591 renal angioplasties in 419 patients with significant renal artery
      stenoses. Clinical and angiographic follow-ups were performed up until 1996.
      RESULTS: In patients with atherosclerotic disease, the acute success rate was
      94%, primary patency 60%, and secondary patency 74%. The results were better for
      fibromuscular dysplasia. Patients with the highest blood pressure and those with
      recent onset of hypertension had the largest decrease in blood pressure. Renal
      angioplasty of bilateral stenosis or stenosis to a single functioning kidney
      preserved renal function in patients with normal to moderately reduced renal
      function. There were no overall positive effects on blood pressure and renal
      function in patients with serum creatinine > 250 mumol/l. CONCLUSION: Renal
      angioplasty can be done in selected patients with renal artery stenosis. The
      selection of patients for renal angioplasty is important in order to increase the
      clinical success rate. Clinical as well as angiographic follow-ups for detection
      of restenosis are mandatory.

PMID- 11826457
TI  - [Patients with traumatic spinal cord injuries at the department of neurology,
      Haukeland Hospital 1952-99].
AB  - BACKGROUND: We wanted to study the cause and the segmental level of traumatic
      spinal cord injuries. MATERIAL AND METHODS: All 238 patients (208 men) with
      traumatic spinal cord injuries admitted to the Department of Neurology, Haukeland
      University Hospital in Bergen, Norway, from 1952 to 1999 were included. Data were
      obtained from medical files and studied retrospectively. RESULTS: The initial
      clinical level of injury was the cervical spine in 50% of the patients, the
      thoracic spine in 33%, and the lumbar spine in 18%. Falling (45%) and road
      accidents (35%) were the main causes. The mean annual number of patients with
      traumatic spinal cord injuries increased from three in 1952-60 to eight in 1991
      99; there was an increase in high cervical injuries among those older than 60.
      The proportion of work-related traumatic spinal cord injuries was 42% in 1952-74
      and 26% in 1975-99. INTERPRETATION: Although there has been a reduction of work
      related spinal cord injuries, there is still a potential for further prevention,
      especially among persons of more than 60 years of age.

PMID- 11826458
TI  - [Botulinum toxin A--effect on spasticity].
AB  - BACKGROUND: Severe spasticity may lead to problems of movement and function, pain
      and hygiene, and may be difficult to treat. A team of neurologists and
      physiotherapists evaluated the effect of botulinum toxin A (BTX-A) on spasticity.
      MATERIAL AND METHODS: Ten patients with central nervous disorders were included
      in this study. Function, pain and personal hygiene were assessed before and after
      injections with BTX-A. RESULTS: Nine patients experienced improvement of function
      and/or pain relief. One patient had improved perception in his hand, and one
      patient needed only two injections to stop a vicious circle. The effect varied
      from patient to patient. It seemed that patients with some preserved motor
      control in the spastic limb could use it to learn more appropriate movement
      strategies. INTERPRETATION: We recommend that doctors and physiotherapists work
      together to identify muscle groups that need to be targeted for injection and
      evaluate consequences of the treatment. Injections with BTX-A should be combined
      with physiotherapy.

PMID- 11826460
TI  - [Information to families with hereditary breast and ovarian cancer].
AB  - BACKGROUND: Under Norwegian legislation, persons at risk should make the initial
      contact with the proper health personnel, and not vice versa. It may be argued
      that the physician should be allowed to make contact with persons at risk of
      preventable or curable disorders. MATERIAL AND METHODS: We identified all first
      degree relatives of all 75 BRCA1 mutation carriers diagnosed within a given
      period of time and asked them whether or not they had been informed by their
      relatives. RESULTS: After two years, 60/63 (95%) adult sisters and daughters had
      made contact with us; the remaining three (5%) had been informed. In comparison,
      18/45 (40%) adult brothers and sons had contacted us. INTERPRETATION: The
      legislation constituted no barrier to offering health services to the target
      group. Information on our services had reached all close relatives who could
      benefit from them. This may be representative for curable inherited disorders. We
      examined inherited cancer limited to females; similar studies on inherited
      cancers in males and on other curable inherited disorders should be performed.
      Outside the framework of the present study, we are aware of rare examples of
      distant cousins who have not been properly informed through their families. One
      legally acceptable way of identifying mutation carrier families is to test all
      patients with breast or ovarian cancer for causative mutations. Health services
      should be monitored to make future decisions based on empirical evidence.

PMID- 11826459
TI  - [Mifepristone--a controversial drug with great potential].
AB  - BACKGROUND: Antiprogestins, agents that inhibit the action of progesterone, are
      among the most controversial and yet the more interesting therapeutic compounds
      developed over the past 20 years. MATERIAL AND METHODS: We present a review of
      the literature identified through limited searches on Medline, Cochrane and the
      Internet, with a discussion of the biological, clinical, political and ethical
      aspects of this important drug. RESULTS: The first effective antiprogestin in
      clinical use was mifepristone (also known as RU 486). This agent provides the
      most effective and safest means of medical abortion. It may also be used as a
      contraceptive and delivery-inducing agent and in the treatment of spontaneous
      abortion, ectopic pregnancies, leiomyoma, endometriosis, intrauterine fetal
      death, Cushing's syndrome and progesterone-dependent malignancies.
      INTERPRETATION: The introduction of mifepristone as an abortion-inducing agent
      has created intense political, ethical and moral controversies which have delayed
      clinical investigations and evaluations for potential expanded use.

PMID- 11826461
TI  - [The cytochrome P-450 system].

PMID- 11826462
TI  - [Antibiotic treatment of infectious endocarditis].
AB  - BACKGROUND: Infective endocarditis is a septic condition in which the heart
      valves and the endocardial surfaces are infected, causing bacteraemia. In Norway,
      infective endocarditis is the most common infectious disease of the heart and
      accounts for approximately one case per 1,000 hospital admissions. The mortality
      rate is 15-40%. MATERIAL AND METHODS: This article presents a review of
      antimicrobial treatment of infective endocarditis, based on relevant literature
      and the author's clinical experience. Prophylactic treatment is not described.
      RESULTS AND INTERPRETATION: Early start of antimicrobial treatment is extremely
      important in order to avoid destruction of the heart valves and should always be
      started as soon as endocarditis is suspected and blood cultures have been drawn.
      The patient must be treated with bactericidal antibiotics in high doses given
      intravenously for four to eight weeks, depending on the aetiologic agents and the
      response. Only antibiotics that have been proven effective against endocarditis
      should be used. The minimal inhibitory concentration (MIC) should be determined
      for all antibiotics used.

PMID- 11826463
TI  - [Treatment of acute bacterial meningitis].
AB  - BACKGROUND: Acute bacterial meningitis requires immediate antimicrobial therapy.
      MATERIALS AND METHODS: Guidelines to antimicrobial treatment of children and
      adults with acute bacterial meningitis are presented. RESULTS: The most common
      agents causing acute bacterial meningitis are Streptococcus agalactiae in
      children less than one month of age, and Streptococcus pneumoniae and Neisseria
      meningitidis in individuals more than one month of age. If the causative
      bacterial agent is not known, children below one month of age should be given
      ampicillin and gentamicin, whereas older children and adults should be given
      benzylpenicillin in combination with either cefotaxime or ceftriaxone. We suggest
      treatment with specific antibiotic regimens in cases of known aetiology.

PMID- 11826464
TI  - [Streptococcus group A infections of skin, soft tissue and blood].
AB  - BACKGROUND: Group A streptococcus is one of the most common bacterial pathogens
      causing infections in tissue and organs, most frequently throat and skin. Since
      the late 1980s there have been reports from Scandinavia and many other countries
      documenting a resurgence of highly invasive infections such as puerperal fever,
      necrotizing fasciitis, myositis and sepsis. MATERIAL AND METHODS: On the basis of
      relevant studies and reviews and a clinical study of 61 patients between 1992 and
      1999 with necrotizing fasciitis and myositis at Haukeland University Hospital,
      Bergen, Norway, we present an overview of the prevalence, pathogenesis, clinical
      features and treatment of group A streptococcal infections in skin, soft tissue
      and blood. RESULTS AND INTERPRETATION: The reason for the increase in severe
      group A streptococcal infections is unclear. The clinical features depend on the
      level of infection (superficial skin, subcutis, fascia and muscle): the deeper
      the initial infection, the more frequent development of bacteraemia and life
      threatening disease. Serious infections are associated with shock and multiorgan
      failure, i.e. streptococcal toxic shock syndrome. Early surgical debridement is
      essential in necrotizing fasciitis and myositis. Penicillin is still the drug of
      choice for milder infections. The addition of clindamycin is recommended in cases
      of more invasive infection.

PMID- 11826465
TI  - [Transsexualism and treatment in Norway].

PMID- 11826466
TI  - [Rules concerning "blue prescriptions"].

PMID- 11826467
TI  - [Better health services for lesbian women].

PMID- 11826468
TI  - [Terror against the free world--politics and the Norwegian Medical Society].

PMID- 11826469
TI  - [National medical museum--but how?].

PMID- 11826471
TI  - Audio for bio-communicators: Part 1--The theory of sound.
AB  - As bio-communicators we may provide both the product and equipment an audience
      needs to see and hear a presentation. We also need to understand the physical
      aspects of providing a comfortable listening environment, how that will affect
      the sound and a little bit of the science involved. We also need a guiding
      philosophy to carry this through.

PMID- 11826470
TI  - Evaluation of the computer-based training module for the Marine medic.
AB  - This is a follow-up article (found in JBC Vol. 25, No. 4, 1998) discussing the
      evaluation of the Computer-based Training Module (CBT) presented to the trainers
      of the medical first responders of the health care division of the Marine medics
      at Camp Pendelton, California. Their specific comments are embodied in the text
      of the article. The suggestions provided were to expand the existing CBT Module
      to include enhanced features.

PMID- 11826472
TI  - Technote: a simple technique for comparative wound imaging.
AB  - Photographs of wounds often appear to decrease or increase in size due to the
      distance of the film plane from the wound. These variations in size tend to
      confuse and confound the observer. To accurately depict the healing progress of a
      wound, comparative imaging must be utilized; that is, the "image" of the wound
      must be the same size on the film plane for each exposure. This can only be
      accomplished if the plane of focus and the distance from the wound are constant
      for each exposure.

PMID- 11826473
TI  - Twenty-five years ago in JBPA/JBP.

PMID- 11826474
TI  - Mycobacterium leprae genome sequence; a landmark achievement.

PMID- 11826475
TI  - The decaying genome of Mycobacterium leprae.
AB  - Everything that we need to know about Mycobacterium leprae, a close relative of
      the tubercle bacillus, is encrypted in its genome. Inspection of the 3.27 Mb
      genome sequence of an armadillo-derived Indian isolate of the leprosy bacillus
      identified 1,605 genes encoding proteins and 50 genes for stable RNA species.
      Comparison with the genome sequence of Mycobacterium tuberculosis revealed an
      extreme case of reductive evolution, since less than half of the genome contains
      functional genes while inactivated or pseudogenes are highly abundant. The level
      of gene duplication was approximately 34% and, on classification of the proteins
      into families, the largest functional groups were found to be involved in the
      metabolism and modification of fatty acids and polyketides, transport of
      metabolites, cell envelope synthesis and gene regulation. Reductive evolution,
      gene decay and genome downsizing have eliminated entire metabolic pathways,
      together with their regulatory circuits and accessory functions, particularly
      those involved in catabolism. This may explain the unusually long generation time
      and account for our inability to culture the leprosy bacillus.

PMID- 11826476
TI  - The microbial physiologist's guide to the leprosy genome.

PMID- 11826477
TI  - DNA metabolism in Mycobacterium leprae.

PMID- 11826478
TI  - Genomic evidence for the retention of the essential mycobacterial cell wall in
      the otherwise defective Mycobacterium leprae.
AB  - The obligate intracellularism of Mycobacterium leprae may be attributable to the
      effects of mutations in major metabolic areas due to a genome capable of encoding
      only about 1600 proteins. Yet cell wall biosynthesis capability remains
      relatively intact and comparisons with the genome of Mycobacterium tuberculosis
      provide insights into the genetic basis of a minimal mycobacterial cell wall.

PMID- 11826479
TI  - Genomics and the chemotherapy of leprosy.
AB  - The information deduced from the genome sequence of Mycobacterium leprae is of
      immense value for the chemotherapy of leprosy. Knowing the complete set of genes,
      enzymes and proteins allows us to understand why some drugs are without effect
      whereas others are fully active. It may also enable better use to be made of
      existing drugs, such as beta-lactams, and opens new avenues for the development
      of novel compounds. M. leprae is relatively susceptible to a wide range of drugs,
      unlike the highly related tubercle bacillus, and several new multidrug regimens
      are in clinical trials. Genomics provides a number of possible explanations for
      this broader susceptibility as some of the genes encoding enzymes involved in
      antibiotic inactivation have decayed whereas the number of transporters available
      to contribute to drug efflux is considerably lower than in Mycobacterium
      tuberculosis. Several leads for new drug targets have been uncovered.

PMID- 11826480
TI  - A method for rapid detection of rifampicin-resistant isolates of Mycobacterium
      leprae.
AB  - A genotypic method for predicting rifampicin resistance in Mycobacterium leprae
      has been developed and rigorously tested on mouse footpad-derived and clinical
      specimens. A series of immobilized oligonucleotide capture probes can
      discriminate between wild type and mutant rpoB alleles, and positive controls are
      available for the most frequent mutation affecting Ser425. Two different non
      radioactive detection formats have been tested with comparable success in both an
      industrialized and a developing country. The standardized procedure could now be
      used in a prospective study of potential rifampicin resistance among
      multibacillary patients.

PMID- 11826481
TI  - Repetitive sequences in Mycobacterium leprae and their impact on genome
      plasticity.
AB  - About 2% of the genome of Mycobacterium leprae is composed of repetitive DNA.
      There are more than 26 extinct IS elements together with four families of
      dispersed repeats, present in five copies or more, RLEP (37 copies), REPLEP (15
      copies), LEPREP (eight copies), and LEPRPT (five copies). Although there is no
      sequence similarity to known transposable elements, RLEP occurs predominantly at
      the 3'-end of genes and, in several cases, within pseudogenes, suggesting that it
      was capable of dissemination. Strikingly, on comparison of the genome sequences
      of M. leprae and the closely related tubercle bacillus, Mycobacterium
      tuberculosis H37Rv, many of these repetitive sequences were found at sites of
      discontinuity in gene order. Evidence is presented that loss of synteny,
      inversion and genome downsizing may have resulted from recombination between
      dispersed copies of these repetitive elements.

PMID- 11826482
TI  - The integrated genome map of Mycobacterium leprae.
AB  - The integrated map of the Mycobacterium leprae genome unveiled for the first time
      the genomic organization of this obligate intracellular parasite. Selected cosmid
      clones, isolated from a genomic library created in the cosmid vector Lorist6,
      were identified as representing nearly the complete genome and were subsequently
      used in the M. leprae genome sequencing project. Now a new version of the
      integrated map of M. leprae can be presented, combining the mapping results from
      the Lorist6 cosmids with data obtained from a second genomic library constructed
      in an Escherichia coli-mycobacterium shuttle cosmid, pYUB18. More than 98% of the
      M. leprae genome is now covered by overlapping large insert genomic clones
      representing a renewable source of well defined DNA segments and a powerful tool
      for functional genomics.

PMID- 11826483
TI  - Leproma: a Mycobacterium leprae genome browser.

PMID- 11826484
TI  - [Nitrosomethylurea -- 30 years of study and use in the treatment of cancer
      patients].

PMID- 11826485
TI  - [Reducing of hepatotoxicity of antineoplastic chemotherapy and concomitant viral
      infection through control of liver metabolism: from experiment to clinical
      practice].

PMID- 11826486
TI  - [Aranoza -- a new Russian antineoplastic drug].
AB  - Myelosuppression is a toxicity-related limitation for aranoza dosage. The drug
      proved effective in the treatment of uterine sarcoma, cancer of the head and
      neck, breast, Hodgkin's disease and lymphosarcoma during stage II of clinical
      studies. Complete regression was reported in the treatment of melanoma (ca. 12%).
      Good results of chemoimmunotherapy should be expected in untreated patients as
      well as intraarterial infusions for local lesions of the extremities. Clinical
      trials of aranoza used in combined modalities of therapy in various sites
      continue.

PMID- 11826487
TI  - [Results of a phase I clinical trial of "theraphthal + ascorbic acid" catalytic
      system].
AB  - Phase-I clinical studies of teraphtal and a "teraphtal + ascorbic acid" catalytic
      system have been completed. The dose-limiting toxicity and maximum tolerable dose
      were not reached even at the end of maximal dose trials. No side-effects
      characteristic of antitumor cytostatic drugs were registered. The gravest side
      effect ever recorded was a collapse which could not be linked to teraphtal dosage
      and was probably caused by hypersensitivity to the drug. The drug was recommended
      for phase II trials.

PMID- 11826488
TI  - [Nitrullin -- a new original Russian drug of the nitrosomethylurea group].
AB  - Hematologic thrombopenia and leukopenia formation limits use of nitrullin as a
      toxic hazard. The drug showed moderate effect in treating inoperable non-small
      cell cancer of the lung and satisfactory end results. The treatment had marked
      symptomatic effect in patients with this cancer and, as a consequence, improved
      the quality of life. Nutrullin had immuno-modulating effect. Its application
      alone or in combination with VPN showed good results in the management of small
      cell cancer of the lung.

PMID- 11826489
TI  - [DNA flow cytometry in the prognostication of certain malignant neoformations].
AB  - The study has been concerned with DNA ploidy and its significance for prognosis
      of different neoplasms. The investigation included 314 patients: primary cancer
      of the lung (96), head and neck (146) and large bowel (72). Patients received
      surgery alone or surgery plus either radiotherapy or chemotherapy; they were
      followed up for 6-20 months. DNA levels were assayed in resected material using
      an ICP-22 flow cytometer. Diploid and aneuploid cancers were detected in 20.4
      53.6 and 43.6-79.6%, respectively. The recurrence rates in cases of aneuploid
      cancers were more than 3 times those of diploidy (21.0-43.2 and 4.5-14.5%,
      respectively). Overall 5-year survival in diploid patients was twice that in
      aneuploid ones. Similarly, survival after surgery alone, preoperative
      chemotherapy and postoperative radiotherapy among diploid patients was longer
      than in aneuploid ones. Hence, DNA ploidy examination of tumors is of great
      informative value in prognosing tumor process and working out individually
      tailored approach to treatment.

PMID- 11826490
TI  - [Certain aspects of neoadjuvant therapy of locally advanced breast cancer].
AB  - The paper presents the results of a complex investigation of patients with
      locally-advanced breast cancer who received neoadjuvant chemotherapy or
      chemoradiation at initial stage. The clinical and pathomorphological effects,
      nature of neoadjuvant therapy and number of courses were followed up for 5- and
      10-year periods. A direct correlation was found between number of courses for
      chemotherapy-sensitive patients, on the one hand, and greater effect, more
      intensive medicinal pathomorphism and longer recurrence-free survival,
      particularly, at later stages, on the other.

PMID- 11826491
TI  - [Preclinical toxicological study of theraphthal-Lio and binary catalytic system
      "theraphthal-Lio+ascorbic acid"].
AB  - Pre-clinical toxicologic studies were conducted of a new drug teraphtal-Lio (TPh)
      and a teraphtal-Lio + ascorbic acid (TPh + AA) catalytic system recommended for
      binary catalytic therapy of malignant tumors. Quantitative criteria for "acute"
      and "chronic" toxicity of TPh and TPh + AA were established, which describe their
      toxic effects in single or multiple application. The coefficient of specific
      sensitivity and cumulation index for TPh and TPh + AA were determined. The
      toxicodynamic characteristics of TPh and TPh + AA were investigated. The results
      were used to prognose pulmonary, cardio-vascular, hemato- and hepatotoxic as well
      as hemodynamic and ophthalmologic disorders and functional changes in the central
      nervous system involved in clinical use of TPh and TPh + AA.

PMID- 11826492
TI  - [New models of experimental chemotherapy of tumors].
AB  - New neoplastic models such as orthotopic solitary hepatic tumor
      (cholangiocellular cancer PC-1) as well as different strains of malignant
      pleuritis (hemoblastosis and ascitic tumors) have been evolved by transplanting
      tumor cell suspension to rat liver or murine pleural cavity. Intrahepatic cancer
      PC-1 has a solid mucosa-excreting structure and is characterized by low activity
      of detoxication enzymes of such xenobiotics as glutathione-S-transferase, NAD(p)N
      chinonoxyreductase and aldehyde dehydrogenase. Orthotopic hepatic tumor PC-1 may
      be used for evaluating systemic and regional therapy. Models of tumorous
      pleuritis described with respect to their response to chemotherapy, may have an
      application in screening and preclinical examination of newly-developed antitumor
      drugs.

PMID- 11826493
TI  - [Current results and perspectives of the use of human tumor cell lines for
      antitumor drug screening].
AB  - Cytotoxic screening of 2,000 chemical compounds against human tumor cell lines
      has identified certain antimetabolities, platinum complexes, actinomycin D
      derivatives and somatostatin analogs as possible antitumor agents. Differential
      sensitivity of such lines derived from five cancers (lung, colon, ovary, breast
      and leukemia) to certain antitumor agents has been established. This panel of
      cell lines is currently employed as a model for in vitro drug screening to
      identify biological response profile at earlier stages.

PMID- 11826494
TI  - [Toxicity of binary "theraphthal-Lio+ascorbic acid" (TPH+AA) catalytic system
      during different methods of regional intra-arterial administration in dogs].
AB  - A binary teraphtal-Lio + ascorbic acid (Tph + AA) catalytic system has been
      tested for untoward side-effects using three procedures of regional intraarterial
      infusion on dogs. On the basis of the data on local-tissue and overall toxicity,
      an optimal one was selected and recommended for clinical use.

PMID- 11826495
TI  - [Effects of theraphthal-Lio on hemostasis in experimental animals].
AB  - Teraphtal-Lio (Tph) exerted a toxic dose-dependent effect on the hemostatic
      system. Treatment of experimental animals with maximum tolerated and highly toxic
      doses was followed by acute DVS syndrome formation involving a hemophilic
      condition, soaring activated partial prothrombin time, absence of fibrinogen,
      sharp rise in fibrinogen degradation product and D-dimer matched by fall in
      thrombocyte count. No toxic influence on the hemostatic system was registered
      when Tph doses recommended for humans in the course of phase II clinical trials
      were administered to animals.

PMID- 11826497
TI  - [Results of cooperation of Experimental and Clinical Chemotherapy, N. N. Blokhin
      Center for Oncology Research, Russian Academy of Medical Sciences (1952-2000)].
AB  - Milestones of the Russian antitumor chemotherapy development inseparably
      associated with the names of N.N. Blokhin, L.F. Larionov and V.I. Astrakhan are
      reviewed. Since the early 50s of the last century, more than 7,000 generic and
      synthetic compounds have been studied by the three generations of chemotherapy
      researchers. 17 antitumor drugs have been developed and passed for clinical
      trials, 11 of them have been or still are being used in clinic.

PMID- 11826496
TI  - [New recommendations for evaluating the effectiveness of treatment of solid
      tumors and principles of the Guidelines for Clinical Practice (GCP)].
AB  - A new WHO protocol for measuring tumor during clinical studies using upgraded
      methods of tumor diagnosis was released in 1994. The recommendations based on the
      examination of over 4,000 patients included measuring greatest diameter of tumor
      and evaluation of treatment effect by changes of a sum total of largest
      diameters. Therapeutic effect is established by a decrease in the sum by at least
      30%, while tumor progression--by an increase by at least 20%. The GCP provide
      standards for planning, implementing, monitoring, auditing and documentation of
      clinical trials and submitting their findings. These standards guarantee the
      accuracy and reliability of data, patients' rights of health protection and
      anonymity of those taking part in trials. Today, these rules are binding for the
      European Community, Japan and the USA. All Russian medical establishments running
      clinical tests are to observe the rules.

PMID- 11826498
TI  - [Combination of taxotere and doxorubicin in chemotherapy of disseminated breast
      cancer].
AB  - Chemotherapy (taxotere + doxorubicin) was given to 46 patients with disseminated
      breast cancer: first line--27 (group A) and second line (including treatment
      after anthracycline-containing combinations and taxol--19) (group B). Average
      effectiveness in group A was 70.4% (10/27); group B--42.1% (8/19). The highest
      response was shown by metastases to the lung, liver, peripheral lymph nodes and
      primary tumors; least response--metastases to bones and soft tissues. Remission
      duration ranged 3-26 months. Median remission duration in group A was
      significantly longer than in group B (13.3 +/- 1.0 and 7.0 +/- 1.4 months,
      respectively) (p(0 < 05). Remission is still on in 11 patients (more than 26
      months). Toxic poisoning was moderate: neutropenia stage III-IV was reported in
      82/225 cycles (36.4%) lasting more than 7 days in 4/225 cycles (1.7%), febrile
      neutropenia stage 1-II--10/225 cycles (4.4%); stomatitis and diarrhea stage III
      IV--1/225 cycles (0.44%). Treatment was suspended because of hypertension in one
      patient. No other side effects stage III-IV were registered.

PMID- 11826499
TI  - [Irinotecan and tomudex in the treatment of patients with advanced cancer of the
      large intestine].
AB  - The data on the treatment of 82 patients with advanced colorektal carcinoma are
      presented. Tomudex was given as first-line treatment to 18 cases. Apparent
      response was reported in 31% including complete (6%) and partial (25%)
      regression. Tumor growth control (apparent response + stabilization) was
      registered in 62%. Median survival rate was 38.4 weeks. Neutropenia, diarrhea and
      hepatotoxicity formation limited the modality. The treatment can be recommended
      for out-patients thanks to good tolerability and practical convenience. The
      following regimens of irinotecan were employed as first- and second-line
      chemotherapy (64): 250-350 mg/sq.m, every three weeks (44) and 100-125
      mg/sq.m/week, x 4 every 6 weeks (20). Response was 15 and 16%, tumor growth
      control--60 and 63%, median survival--41.6 and 51.6% weeks, respectively. Leuko-
      and neutropenia and diarrhea development limited both regimens. Weekly infusions
      seemed to offer more advantage for out-patient treatment, particularly, in feeble
      patients and those who are a high risk for grave side-effects. Tomudex and
      irinotecan toxicity was predictable, moderate, reversible and non-cumulative.

PMID- 11826500
TI  - [Combination therapy including mutamycin (mitomycin C) in the treatment of
      advanced colorectal and gastric cancer].
AB  - The paper reports the data on treatment of 57 patients with disseminated gastric
      and colorectal carcinoma using a combination of mutamycin + 5-fluorouracil +
      leucovorin + cisplatin. Overall response was 26.3% including complete--7.01 and
      partial--19.29%. Mean duration of complete and partial remission was 10.88 +/-
      5.65 and 5.18 +/- 0.82 months, respectively. Treatment as first-line chemotherapy
      was significantly more effective (36.1 and 9.5%). The regimens proved relatively
      low-toxic and therefore, can be recommended for out-patient application.

PMID- 11826502
TI  - [Chemotherapy of malignant head and neck tumors in ambulatory care].

PMID- 11826501
TI  - [Combination therapy of patients with locally advanced breast cancer].
AB  - The investigation involved 30 patients with locally advanced breast cancer (T3
      4N1-2M0). Combination therapy comprised two courses: carboplatin 300 mg/m2, i.v.,
      dropwise, on day 1; doxorubicin 30 mg/m2, i.v., bolus-flow, on days 1 and 8; 5
      fluorouracil 350 mg/m2, i.v., bolus-flow, on days 1 and 8, and irradiation of the
      breast and regional metastasis area (single target dose--2 Gy, total target dose-
      40 Gy). Overall clinical response was 96.7% (29/30), mammography-wise--83.3%
      (25/30). All patients were found operable and radical mastectomy was performed in
      25. Therapeutic effect stage III-IV was histologically confirmed in 40% (25/30),
      stage I-II--60% (15/25). Median overall and recurrence-free survival was not
      reached within 36 months in 24/30, relapse-free survival was been reported in
      16/24 (66.6%), tumor progression--8/24 (33.4%). Three-year; host-mastectomy
      recurrence-free survival--68.8 +/- 16.0%.

PMID- 11826503
TI  - [Effectiveness of treatment of recurrences of non-Hodgkin's lymphoma after
      combined chemoradiotherapy depending on prognostic indicators].
AB  - The results were evaluated of the management of non-Hodgkin's lymphomas in 46 out
      of 150 patients relapsing after first complete remission, following early-stage
      chemoradiotherapy. Polychemotherapy of recurrent tumors was given to 85% (39/46),
      repeat combined treatment--13% (6/46) and radiotherapy--2% (1/46). Remission was
      reported in 91% (42/46): complete--69% (32) and partial--22% (10). Remission
      frequency and duration directly depended on degree of risk (IPI), stage of
      recurrence development and advancement, tumor size and general symptoms of
      intoxication. There was no relationship between frequency and duration, on the
      one hand, and sex and age, tumor pattern or number of involvement areas, on the
      other. Instead, the efficacy was influenced by the general condition of the
      patient, damage to the lymph nodes rather than adjacent areas as well as number
      of such areas. LDH blood level impacted the end results.

PMID- 11826504
TI  - [Results of phase II clinical trial of cycloplatam in refractory solid tumors].
AB  - Cycloplatam, a new platinum derivative, evolved at N.S. Kurnakov Institute of
      General and Inorganic Chemistry in 1982, has been added to the arsenal of Russian
      cytostatic drugs. Having passed phase I trials, it was approved for treatment of
      pleural mesothelioma, ovarian carcinoma and multiple myeloma.
      Leukothrombocytopenia formation indicates toxicity-related limit of dosage. Phase
      II clinical trials are under way at the Center. They include treatment of solid
      tumors with cycloplatam alone in urinary bladder tumors, cervical carcinoma and
      malignant pleurites of various etiology as well as in combination with other
      cytostatics (carcinoma of the prostate, pleural mesothelioma and urinary bladder
      tumors). The drug may be recommended both for oral and intracavitary
      administration; side-effects may include moderate toxicity, chiefly,
      hematological one.

PMID- 11826505
TI  - [Present-day possibilities of the treatment of small cell cancer of the lung].

PMID- 11826506
TI  - [History of the Department of Clinical Chemotherapy, N. N. Blokhin Center for
      Oncology Research, Russian Academy of Medical Sciences, and its role in the
      development of Russian drug therapy of malignant tumors].

PMID- 11826507
TI  - [Professor V. I. Astrakhan -- founder and leading mastermind of the scientific
      course of clinical chemotherapy in Russia].

PMID- 11826508
TI  - From the laboratory to pharmaceutical care research--Part I.
AB  - In pharmaceutical care research (PCR) a mass of robust general rules has not yet
      been found. Consequently, the challenge of PCR is that mainly through induction
      researchers have to study objects which are learning and which are open to
      environmental influences and, by doing so, researchers have to contribute to both
      theory and practice. Therefore the characteristics reductionism, repeatability
      and refutability originated from natural sciences cannot be applied to PCR on a
      1:1 basis. PCR should be imitable, defensible, consistent and relevant in order
      to enable other researchers to agree or disagree with the conclusions and to
      stimulate new research.

PMID- 11826509
TI  - Pharmaceutical care and medicines management--is there a difference?

PMID- 11826510
TI  - The design and evaluation of a simulated-patient teaching programme to develop
      the consultation skills of undergraduate pharmacy students.
AB  - OBJECTIVES: This study aimed to identify the key skills and knowledge required
      for the delivery of an ideal patient consultation in order to develop a training
      programme (using simulated-patients) to teach consultation skills to
      undergraduate pharmacy students. METHODS: Participants included all third year
      undergraduate Pharmacy students (MPharm, level III) at the School of Pharmacy &
      Biomolecular Sciences, University of Brighton (from October 1999 to March 2000).
      Working in groups of 12, students participated in two 4 hour seminars. A
      structured questionnaire was designed to assess students' perceptions of the
      difficulty of conducting a consultation and their confidence in delivering a
      structured consultation. MAIN OUTCOME MEASURES: Questionnaires were administered
      before and after delivery of the teaching programme to assess changes in
      students' confidence and ability to consult with patients. RESULTS: Twelve
      volunteers satisfied the criteria set to serve as simulated patients and then
      received appropriate training. Six scenarios were developed which focused on the
      key skills and knowledge identified from the adherence and consultation skills
      literature. A total of 91 students participated in the programme (mean age = 23
      years, SD = 4.5). Following participation in the programme students' perceived
      'confidence' for conducting an effective consultation significantly increased (t
      = -5.9, p < 0.01) while a statistically significant decrease was seen in
      students' perceived level of 'difficulty' when conducting a consultation (t =
      4.0, p < 0.01). CONCLUSION: This study has shown that the use of a structured
      teaching programme improves students' perceptions of their ability and confidence
      in conducting an effective consultation. Providing skills training around the
      consultation process, using simulated patients, provides pharmacists with a good
      framework around which to practice pharmaceutical care.

PMID- 11826511
TI  - Italian drug information centres: benchmark report.
AB  - OBJECTIVE: Pharmacist-operated Drug Information Centres (DICs) in Italy were
      surveyed to gather current information concerning the status, availability and
      scope of their services. METHODS: 40 DICs were identified and a questionnaire was
      mailed to them. Topics covered in the questionnaire included staffing, resources,
      activities and services. The results were compared with previous survey results
      to identify trends. RESULTS: Information from 36 DICs was analysed (response rate
      = 90%). Almost all regions of the country are represented. Pharmacists, part-time
      or full-time, are the most frequent employees working in the DICs. 91% of DICs
      participate in the P/T committee, 74% takes part in the technical scientific
      committee for clinical experimentation and/or to the Medical Ethics committee and
      60% participate in the hospital infection committee. 90% of DICs produce
      newsletters and/or bulletins and are involved in research projects. Regarding the
      question-answer service, requests are mainly concerned with clinical comparative
      efficacy, therapeutic use, adverse effects. The most frequent users are
      physicians (67%) followed by pharmacists (16%) while other professionals use DICs
      to lesser extent. The most frequently used information sources, include "Goodman
      and Gilman's the pharmacological basis of therapeutics", Martindale: the Extra
      Pharmacopeia and Physician's Desk Reference; journals such as the Medical Letter,
      Adverse Drug Reactions Bulletin and Drug and Therapeutic Bulletin, Micromedex,
      Medline and IOWA databases. Data collected through the questionnaire and details
      about organisation and activity of Italian DICs are available in "Eupharma", the
      web-site of the Italian Society of Hospital Pharmacy (SIFO) at the URL
      http://www.sifo.it. CONCLUSION: The results parallel the European and American
      trends. In future communication and collaboration at European level could help to
      identify best practice models that would result in the standardisation of the
      activities and in the harmonisation of programs in common areas of interest.

PMID- 11826512
TI  - Assessing the effects of an intervention by a pharmacist on prescribing and
      administration of hypnotics in nursing homes.
AB  - INTRODUCTION: We have previously reported sub optimal use of hypnotics in
      geriatric institutions. In the present study we examined the intervention by a
      pharmacist on the prescribing and administration of hypnotics in nursing homes.
      Thus a follow up study was performed in 5 nursing homes included in the previous
      study. METHOD: In the period between the two surveys the pharmacist provided drug
      information on the rational use of hypnotics, both written and verbal, to the
      staff of the institutions. Data on the administration of hypnotics was obtained
      from the Cardex system in the institutions. Data were compared to a control group
      in other nursing homes, where no intervention was carried out. RESULTS: Although
      the population was older in 2000 than in 1995, the proportion of patients using
      hypnotics (24%) was similar. Use of benzodiazepines was reduced from 81% to 40%,
      use of long acting benzodiazepines was reduced from 62% to 22%, and use of short
      acting hypnotics (zopiclone, zolpidem) increased from 9% to 53%. Furthermore,
      hypnotics administered before 9 p.m. were reduced from 40% to 14%, and the time
      of administration showed less variation than before. In the control population we
      also observed the use of short acting hypnotics in favour of benzodiazepines,
      similar to the results in the 5 institutions. However, in this population a
      significantly higher proportion of patients used hypnotics, used more than 1
      hypnotic and the hypnotics were administered earlier in the evening. CONCLUSION:
      The results demonstrate an important effect of written and verbal drug
      information provided by a pharmacist to improve the prescribing and
      administration on the use of hypnotics in nursing homes.

PMID- 11826513
TI  - Variability in prescribing for musculoskeletal pain in Finnish primary health
      care.
AB  - OBJECTIVE: To assess primary care physicians' prescribing patterns for
      musculoskeletal pain in different diagnostic categories. METHODS: The data were
      collected in 25 randomly selected health centres, in which a total of 28
      physicians took part in the four-week study. Physicians recorded all the
      medicines they prescribed for patients visiting due to pain. Visits resulting in
      a diagnosis of musculoskeletal disease or injury were included in this study.
      RESULTS: Analgesics, including non-steroidal anti-inflammatory drugs (NSAIDs),
      were prescribed for 61% of the patients. NSAIDs were prescribed for 46%, topical
      analgesics for 15% and opioids for 4% of the patients. In general, ibuprofen was
      the most frequently prescribed drug but back and neck pains were most commonly
      treated with naproxen. No difference between patients' genders was observed in
      analgesic prescriptions. Prescribing was associated with patient's age,
      physician's view on priority of visit, diagnosis and intensity of pain. There was
      a large variation in prescribing patterns between individual physicians and
      between different areas of the country. CONCLUSION: NSAIDs are the prevailing
      treatment for musculoskeletal pain in Finnish primary health care. Different
      drugs are favoured according to the diagnosis. The large variability in
      prescribing patterns cannot be explained solely by the characteristics of pain or
      patients.

PMID- 11826514
TI  - Questions elderly patients have about on-going therapy: a pilot study to assist
      in communication with physicians.
AB  - PURPOSE OF THE STUDY: This pilot study examined the prevalence and types of
      questions elderly patients have about their current drug therapy. It also
      evaluated the effectiveness of a brief intervention to prepare patients to ask
      questions about drug therapy during medical visits. DESIGN AND METHODS: The
      research used a posttest-only experimental design. Forty-five elderly patients
      seen at a primary care clinic during a one-month period consented to participate
      and completed the study. After consent, subjects were randomly assigned to
      intervention and control conditions. A brief interview with intervention group
      subjects conducted by a medical student assigned to the clinic as part of a
      summer research experience helped subjects formulate questions they had about
      current therapy before they went into medical visits. Patient-physician visits
      were audiotaped and patient questions about medications and health care were
      tallied. RESULTS: Subjects in the intervention group were significantly more
      likely to ask questions of providers than were subjects in the control group.
      Intervention group subjects were found to ask a wider variety of medication
      related questions than were control group subjects, including questions related
      to proper use, problems perceived with medications, and effectiveness of
      treatment. IMPLICATIONS: Assisting patients to formulate questions before medical
      visits results in an increased likelihood that patients will ask questions and
      will ask a wider variety of questions during the medical visit.

PMID- 11826515
TI  - Do asthma patients receive sufficient information to monitor their disease--a
      nationwide survey in Finland.
AB  - OBJECTIVES: The aim of this study was to assess to what extent the principles of
      asthma monitoring are implemented among Finnish asthma patients and if the
      patients have received sufficient information to adjust their medication
      according to asthma symptoms. SETTING: All Finnish asthma patients receiving
      asthma medication from Finnish community pharmacies during two days in June 1998.
      MAIN OUTCOME MEASURES: The proportions of asthma patients who monitor their
      asthma status according to the national guidelines and have received specific
      instructions on how and when to adjust their asthma medication. RESULTS: Eighty
      six per cent of the respondents (86%) monitored their asthma status on a method
      recommended by the national guidelines. They made Peak Expiratory Flow (PEF)
      measurements (39% of the respondents), they monitored their symptoms (34%) or
      both (13%). A smaller proportion of the respondents (58%) were instructed on
      adjusting their medication according to symptoms. The lowest rates for monitoring
      the asthma status was found among the elderly (65 years or more) and among those
      who reported that they had been on medication for longer than 5 years (17% and
      13% of the subgroup populations, respectively). The lowest rates for having
      received specific instructions on adjusting their asthma medication according to
      symptoms were found among the elderly (36%), among those who reported that they
      had been on asthma medication less than one year (44%), and among males (54%).
      CONCLUSIONS: Pharmacists and other health care professionals need to enhance
      their education activities and their co-operation in training asthma patients to
      monitor their disease, especially principles of adjusting medication according to
      symptoms. In this process, especially the training needs of the elderly patients
      and those who have been using asthma medicines for a long time need to be taken
      into account.

PMID- 11826516
TI  - [Immunodiagnosis of neurocysticercosis: comparative study of antigenic extracts
      from Cysticercus cellulosae and Taenia crassiceps].
AB  - Different antigenic extracts of Taenia solium and Taenia crassiceps were
      evaluated in connection with the detection of antibodies in patients with
      neurocysticercosis aimed at selecting immunorelevant antigens for the diagnosis
      of neurocysticercosis by means of the immunoenzymatic assay and immunoblotting.
      The vesicular fluid of T. crassiceps proved to be more sensitive (100%) and
      specific (86%). On using the immunoblotting technique it was also observed that
      this extract was the most sensitive and specific. Within the protein profile of
      the antigen the band of 18 kDa was mostly recognized by the serum and
      cerebrospinal fluid of patients with neurocysticercosis. The vesicular fluid of
      T. crassiceps represents an alternative in the optimization of the diagnosis of
      neurocysticercosis in the serum and cerebrospinal fluid and in the substitution
      of T. solium antigens due to its high sensitivity and specificity and to its easy
      obtention under controlled laboratory conditions.

PMID- 11826517
TI  - [Identification of a neutral protease in the intestine of Boophilus microplus
      with electrophoresis in polyacrylamide gels copolymerized with gelatin].
AB  - A neutral activity of Boophilus microplus in the intestine was identified by
      electrophoresis in polyacrilamide gel copolymerized with gelatin. The maximum of
      activity was attained at pH 6.0. The highest specific activity at that pH was
      obtained with casein substrate. The disappearance of this activity was observed
      in both substrates after the addition of phenylmethylsulphonyl fluoride in the
      reaction mixtures. It was very interesting to find out an endopeptidase activity
      with these characteristics in the intestine, in spite of the fact that the
      digestive activity in ticks is intracellular at very acid pH, which does not
      occur in other insects.

PMID- 11826518
TI  - [Typing habitats of Aedes albopictus in Cuba and their association with other
      species of Culicidae, 1995-1998].
AB  - A typing of the habitats of Aedes albopictus in Cuba was made after its detection
      in 1995. It was observed in suburban areas of the Boyeros Municipality, in Havana
      City, where a study was conducted from October, 1995, to July, 1998. Most of the
      positive repositories were found outside the houses. Tins, tires, trees and
      plants were the places preferred for its breeding. It was found in the breeding
      places associated with Aedes mediovittatus and Culex quinquefasciatus, dominant
      species in these places. It was also observed a trend towards an increase of the
      number of repositories colonized only by the species under study. Reference was
      made to the phenomenon of competence between this species and the indigenous
      species present in such places.

PMID- 11826519
TI  - [Incidence of Aedes (S) aegypti and other Culicidae in the municipality of Playa,
      La Habana City].
AB  - An analysis was made on the incidence of Culicidae present in Playa Municipality,
      Havana City, during the intensive stage of the anti-aegypti campaign from June to
      July, 1997, according to its requirements. Culex quinquefasciatus was the
      predominant species with a total of 269 focuses. It was collected in all the
      People's Councils and in every type of repository, excepting clay repositories.
      The second most abundant species was the Aedes aegypti with 199 focuses, followed
      by Aedes mediovittatus with 67. The Almendares-Sierra, Ampliacion-Almendares and
      Miramar People's Councils showed the highest values of Culicidae infestation in
      the municipality. The Aedes aegypti prevailed in the first and Cx.
      quiquefasciatus in the second. The artificial repositories, low tanks and other
      repositories had the highest number of mosquito focuses in the municipality. The
      Cx quinquefasciatus preferred the artificial depositories, whereas the A. aegypti
      preferred the low tanks. Most of the positive depositories were colonized by only
      one species (92.7% of the total). 7.3% corresponded to mixed focuses. It was
      found that Cx. quinqufasciatus and A. aegypti were the most associated species.

PMID- 11826520
TI  - [Course of insecticide resistance in Culex quinquefasciatus (Diptera: Culicidae)
      in a region of La Habana].
AB  - The use of malathion to control mosquitoes in Cuba during 7 years until 1986
      selected 2 resistance mechanisms: that of elevated activity of nonspecific
      esterases and that of altered acetylcholinesterase (Ache) in Culex
      quinquefasciatus (Say). In Havana, specifically in the area under study (Quibu
      River), malathion was replaced by cypermethrin in 1987 and cycles of treatment
      with cypermethrin have been intensively used since 1987 up to now when the
      populations of Aedes or Culex increase. In Culex quinquefasciatus (Say) from the
      Quibu River the resistance levels, mainly to malathion, declined significantly
      from 1986 to 1997. An increase of resistance to pyrethroid was observed during
      that period of 11 years. The mechanism of elevated esterases rose to a frequency
      of 1 and there was also an increase in the frequency of the mechanism of Ache.
      The esterase B1, responsible for the resistance to malathion, but not to
      pyrethroid, was selected in this population until 1986. Starting from the use of
      pyrethroid for the control in this area, 2 new phenotypes of esterases named A6
      and B6, apparently related to pyrethroid resistance, were selected.

PMID- 11826521
TI  - [Obtention, characterization of antigens and evaluation of the immunotransfer
      technique for the detection of systemic candidiasis].
AB  - A culture media containing peptone, glucose, yeast extract and serum was
      evaluated to promote the development of the mycelium formation in Candida
      albicans and it was compared with the commercial media Tc 199. No significant
      difference was found between them. Somatic antigens characterized by PAGE-SDS
      were obtained from yeast and mycelial forms. Proteins reported as having high
      diagnostic value were expressed in both antigens. It was determined by
      immunotransference that the antigenic proteins predominating in the mycelium
      formation had molecular weights of 19, 21, 27 and 57 Kda. The immunotransference
      was standardized for detecting antibodies in patients with systemic candidiasis.
      24 positive sera were evaluated by this technique and it was compared with the
      ELISA technique, which proved to be more sensitive and less specific. The most
      recognized proteins were those of 136 and 21 Kda and the complex from 42 to 45
      Kda.

PMID- 11826522
TI  - [Sensitivity of clinical isolates of Candida albicans to 5-fluorocytosine].
AB  - 5-fluorocytosine has been one of the most used antimycotics in the therapeutics
      of mycosis, however the appearance of resistant strains may be an important
      limitant for its use. That's why it is necessary to know the sensitivity to this
      drug. To this end, it was determined the minimum inhibitory concentration (MIC)
      of 5-fluorocytosine against 50 clinical isolates of Candida albicans by a
      micromethod of dilution in RPMI 1640 media, comparing 2 reading methods. The
      values of the geometrical mean obtained were 0.95 mg/mL for the visual reading
      and 0.75 mg/mL for the automated reading. There were no significant differences
      between them (p < 0.05). Pearson's lineal correlation coefficient was r = 0.81.
      It indicates that although there was a good correlation, there was also
      discrepancy between both readings. The IMC50 was of 0.5 microgram/mL and the
      IMC90 of 4 mg/mL. 90 and 92% of sensitive strains, between 6 and 8% of resistant
      strains and 2% of strains with intermediate sensitivity were found depending on
      the reading method used. These values show a low resistance against this drug,
      which may have a direct repercussion on the therapeutic behaviour to be followed
      in candidiasis.

PMID- 11826523
TI  - [Dengue virus-specific antigen lymphoproliferation assay with human T cells].
AB  - Papers dealing with the study of the immune response to dengue virus infection
      and with the role it may play in the pathogenesis of dengue hemorrhaghic fever
      are increasingly important. The memory human T cell response in individuals with
      history of dengue infection during the Cuban epidemic was studied in this paper
      for a further evaluation of the antigenicity of viral proteins. To this end,
      mononuclear cells of peripheral blood from individuals immune to dengue and from
      a group of control subjects with viral antigens were incubated. It was obtained a
      significant proliferative response of lymphocytes from individuals with history
      of infection against dengue virus type 2 compared with control subjects. It was
      proved this way the dengue virus-specific memory T CD4+ cell response in the
      individuals under study.

PMID- 11826524
TI  - [Monitoring of cytomegalovirus infection in patients with kidney transplantation:
      the first experience in Cuba].
AB  - Kidney transplantation is at present the most efficient therapeutic tool to treat
      end-stage chronic kidney failure. Graft rejection and infections are the most
      important barriers to the success of transplantation, whereas cytomegalovirus
      (CMV) has been the most reported causal agent of morbidity in this type of
      patients. The evolution of a group of 12 patients who underwent kidney
      transplantation at the Nephrology Institute was studied during 16 weeks aimed at
      monitoring the infection caused by CMV. 58.4% of these patients were positive and
      28% showed clinical evidences of the disease. Most of the infected patients were
      observed between the 4th and the 12th week after transplantation. CMV infection
      was confirmed in 70% of the individuals undergoing a high immunosuppression. 50%
      of the total of patients developed graft rejection episodes some time during the
      evolution and 83.3% were diagnosed CMV infection.

PMID- 11826525
TI  - [Presence of measles virus antibodies in a group of patients with malignant
      hemopathy].
AB  - 225 monosera from patients (121 adults and 104 children) with different malignant
      haemopathies from the Institute of Hematology were studied. The hemagglutination
      inhibition (HI) technique and the neutralization technique were used to know the
      presence of antimeasles antibodies. All these patients were under
      immunosuppression treatment at the time of taking the specimen and children had
      received the triple viral vaccine (measles, rubella, parotiditis) before the
      disease was diagnosed. It was found that 51 (42.14%) of the adults' specimens
      were positive by HI and of the 25 negative specimens that underwent the
      neutralization technique, 18 (72%) proved to be positive. Of the 104 sera
      corresponding to children, 31 (29.8%) specimens were positive by HI, whereas 29
      of the negative were studied by neutralization. 18.34% of all the specimens
      continued to be negative by both methods. According with the 2 techniques used,
      the presence of measles virus antibodies was of 81.66% in children and of 90.78%
      in adults.

PMID- 11826526
TI  - [Biological behavior of 3 strains of the dengue-2 virus in 2 cell lines of
      mosquitoes].
AB  - Strains A-15 (isolated in Cuba, 1981), Jamaica (isolated in Jamaica, 1981) and
      Nueva Guinea "C" (standard) from dengue-2 virus were compared according to the
      time of appearance of the cytopathic effect (CPE), to the time of appearance of
      specific fluorescence and to the kynetics of viral multiplication on being
      innoculated in the cell lines AP-61 (Aedes pseudoscutellaris) and C6/36 HT (Aedes
      albopictus). The results showed that the CPE of highest intensity and earliest
      appearance was for A-15, followed by Jamaica and Nueva Guinea "C" (NGC). AP-61
      seems to favor the CPE of Jamaica with respect to that of the same strain in
      C6/36 HT. The fluorescence was earlier for Jamaica and A-15 and more intensive
      for the latter, whereas NGC manifested late. This behaviour was similar in the 2
      cellular systems. The greatest titres during the kinetics of viral multiplication
      were obtained from A-15 in both lines, although in AP-61 they tend to be equal
      from the 4th day on. The strain A-15 showed a particular behaviour of these
      biological properties on comparing them with the other strains under study, which
      may be related to changes found in its neucleotide sequence.

PMID- 11826527
TI  - [Mother to child transmission of infantile HIV/AIDS in Cuba].
AB  - The number of children born to HIV/AIDS-seropositive mothers in Cuba is small due
      to the implementation of the program for the prevention of maternal-infant
      transmission of HIV/AIDS in Cuba. During the studied period (January 1st, 1985,
      to December 31st, 1999) 64 children were born, 9 were infected with HIV, 7 of
      them have developed AIDS (3 have died due to this cause and 4 are under treatment
      with antiviral agents and proteases inhibitors) and 2 are asymptomatic HIV
      seropositive. Of the 48 children that concluded the study, 39 (81.25%) are sound
      and 9 (18.75%) are HIV/AIDS-seropositive children, which is a low figure of
      maternal-infant transmission compared with that of the developed countries. Since
      1997, when AZT began to be administered to mothers and children, none of the 8
      children that finished the study have been infected. Up to now, 10 HIV/AIDS
      seropositive children, 9 by perinatal route and 1 by blood transfusion, already
      dead, have been reported in the country.

PMID- 11826528
TI  - [Presence of pediculosis in people living with children positive to Pediculus
      capitis (Anoplura: Pediculidae)].
AB  - In order to determine the frequency of pediculosis in persons living with
      children diagnosed as positive to Pediculus capitis in educational institutions
      of the "Carmelo" People's Council, the houses of 58 children who repeatedly had
      pediculosis from May to September, 1997 were visited. 14.54% of the 237 examined
      persons were positive (40 individuals). 82.5% were females. The mother was the
      most affected relative (32.5%). 30 positive children were matched by age, sex and
      grade with 30 negative children. People living together with the cases had a
      higher frequency of pediculosis (12.4%) than those living with the controls
      (1.8%) (t = 3.49; p < 0.001). The examination and treatment, if necessary, of
      those persons living together with the school children with pediculosis was
      recommended.

PMID- 11826529
TI  - [Side effects of lindane in children with pediculosis].
AB  - The side effects of lindane in children with pediculosis were reported. 2.54% of
      the 551 primary school children who underwent treatment had adverse reactions to
      this drug. It was recommended to increase knowledge about this parasitization and
      to avoid the indiscriminate use of chemicals and other products to eliminate
      lices.

PMID- 11826530
TI  - [Vaginal trichomoniasis in a group of HIV-positive people].
AB  - A total of 132 women who received attention at the Outpatient Department of
      Dermatology of the "Pedro Kouri" Institute of Tropical Medicine from January to
      July, 1998, were studied. 64 of them were HIV carriers and 68 were sound
      controls. On determining the infection frequency by Trichomonas vaginalis, it was
      found that 15.6% and 16.1%, respectively, were parasitized by this protozoa. The
      diagnostic techniques used were simple direct examination of the vaginal exudate
      and culture in vitro. The latter proved to be more sensitive on yielding 100% of
      sensitivity. It was determined that 48 hours was the optimum time for reading
      each specimen.

PMID- 11826531
TI  - [Incidence of dengue in children and adolescents].
AB  - A descriptive study of children and adolescents that got sick with dengue in the
      health area served by "Jose Marti" polyclinics in Santiago de Cuba from May to
      August 1997 was conducted to determine the incidence of this affection in these
      age groups. It was observed that dengue was more frequent in males aged 5-11
      years. Bronchial asthma, epilepsy and congenital cardiopathy were the most common
      previous affections found. The incidence of the disease in the casuistry was low,
      with well-nourished males without histories of chronic processes and good
      clinical recovery prevailing. Only one case was classified as hemorrhagic dengue.

PMID- 11826532
TI  - [Clinical features of dengue fever in children during the outbreak in Santiago de
      Cuba].
AB  - A study of the dengue outbreak occurred from January to November 1997 in Santiago
      de Cuba municipality was performed to characterize the clinical picture of the
      patients. The sample was taken from those patients presenting with clinical and
      epidemiological elements and positive IgM determination serological test. Seventy
      seven patients were confirmed as having dengue virus 2 infection whose clinical
      humoral characteristic was dengue fever predominantly present in school boys. The
      clinical picture was given by fever headache, retrorbitary pain,
      osteomioarticular pain as the most common symptom and by exanthema as a
      prevailing sign. Most of bleedings occurred on the 2nd day and the most frequent
      hemorrhagic manifestation was positive tourniquet test.

PMID- 11826533
TI  - [Characterization of patients with suspected diagnosis of dengue in the outbreak
      of 1997].
AB  - We reviewed the medical histories of the 778 patients admitted to the Military
      Hospital of Santiago de Cuba with presumptive diagnosis of dengue which was
      clinically and epidemiologically confirmed in 423 on discharge and in 24 patients
      from the clinical epidemiological and immunological viewpoints. From the total
      number of patients we selected 54 having alert signs, who were classified by age,
      sex, clinical manifestations and development since they arrive at the Emerging
      Department at 8, 24 and 72 h later and at 5 days. Data were manually and
      automatically processed with an ACER-500 computer. The disease was predominant in
      males under 50 years of age and, in one third of the patients with the alert
      signs, the disease was immunologically verified. The more acute clinical picture
      was observed between 8 h and 24 h of the process but there was no death by this
      cause.

PMID- 11826534
TI  - [Reactive hepatitis caused by the hemorrhagic dengue virus].
AB  - A descriptive lengthwise and prospective study of 37 patients with reactive
      hepatitis caused by hemorrhagic dengue virus, who were clinically humorally and
      ecographically followed up for one year, was made to characterize the disease and
      its development. The results were analyzed as percentages and yielded the
      predominance of the morbid process in females and young people and of fever as a
      symptom and hepatomegalia as a sign. Thrombocytopenia and increased hematocrit
      followed transaminanse levels as the most altered lab values whereas the
      perivesicular edema was the most striking element from the echographic viewpoint.
      The follow-up allowed us to observe a rapid clinical recovery and the
      normalization of transaminanse levels but the persistence of the serine-globulin
      index inversion and of hepatomegalia in almost one quarter of the patients were
      also noted.

PMID- 11826535
TI  - [Adaptation of microtitration plate methods for quantification of the activity of
      esterases and glutathione-s-transferase in Aedes aegypti].
AB  - The detection techniques for the activity of non-specific esterases and
      glutathione-s-transferase in Culex quinquefasciatus were modified to detect such
      enzymes in Aedes aegypti(L). The optimal concentration values of substrate
      (saturating concentration) and the optimum reading time for reaction were
      determined for each enzyme by using 4 Aedes aegypti strains: one from Cuba 2 from
      Venezuela and one susceptible reference strain. The frequency of non-specific
      esterases turned out to be 0.76 in MIRANDA 0.42 in ARAGUA and 1 in SANTIAGO DE
      CUBA in which the highest frequency value of this mechanisms was reached. The
      frequency of glutathione-s-transferase mechanism was 0.45 in ARAGUA 0.043 in
      MIRANDA and 1 in SANTIAGO DE CUBA. For the first time in Cuba a set of
      biochemical techniques was available for detecting the resistance mechanisms of
      Aedes aegypti which made it possible to create sound foundations for the easy
      rapid detection of the resistance of this species the main dengue vector in the
      Americas.

PMID- 11826536
TI  - [High esterases as mechanism of resistance to organophosphate insecticides in
      Aedes aegypti strains].
AB  - Five strains of Aedes aegypti L. one from Cuba and 4 from Venezuela were
      evaluated to determine their resistance to organophosphate insecticides
      (temephos, chlorpiriphos and pirimiphos methyl). In the Venezuelan strains only
      APURE showed resistance to temephos. In TACHIRA and MIRANDA moderate resistance
      values were noted (FR50 5 to 10x) for chlorpiriphos and high levels of resistance
      (FR > 10x) to this insecticide were found in ARAGUA. All the Venezuelan strains
      showed high levels of resistance to pirimiphos methyl. The Cuban strain from
      Santiago de Cuba revealed moderate resistance to temephos and pirimiphos methyl,
      but high resistance to chlorpiriphos. The results of the biochemical tests proved
      the presence of esterase and glutathione-s-transferase at high frequency in
      almost every strain. By the polyacrilamide gel electrophoresis, a strongly
      stained band was observed in all the strains with a Rf value of 0.779; it was
      named esterase A4 and was not seen in the susceptible reference strain. The
      meaning of this esterase in the resistance to organophosphate insecticides is yet
      to be determined. Resistance to these insecticides in Aedes aegypti is a serious
      problem for the control of this species therefore integrated management
      strategies were proposed to prevent or delay the appearance of this species in
      Cuba and Venezuela.

PMID- 11826537
TI  - [The community and the control of Aedes aegypti: perception and behavior
      regarding temephos larvicide].
AB  - Given the persistence of Aedes aegypti foci in the Santiago de Cuba municipality
      in 1998, a survey was made among the dwellers of the houses to find out their
      acceptance and behaviour in relation with temephos, to precise over the reasons
      why the product was not kept in water containers and to know the aspects
      associated with the existence of foci and their control. It was found that there
      were filled water tanks in houses where there was daily water supply so that dirt
      can deposit and water be used later. In 72.2% of the houses, water tanks were
      washed and refilled every 4 day approximately. It was concluded that water
      dirtiness was an additional factor to keep water in tanks, the use of
      temephos(abate) in water tanks for domestic use did not meet the objective
      pursued by this larvicide, the role of fumigation was overvalued and lack of
      appropriate knowledge may influence the behaviour of these surveyed persons.

PMID- 11826538
TI  - [Biologic effect of diflubenzuron on Blattella germanica (Dictyoptera:
      Blattellidae)].
AB  - The Amejeiras strain of Blatella germanica (Dictyoptera: Blattellidae) kept in
      lab conditions since 1994 and susceptible to arpocarb, malathion and cipermethrin
      insecticides, was studied. This strain was treated with 4 diflubenzuron (Dimilin
      OMS 1804) concentrations supplied by feeding nymphs at their first stage of
      development, with the purpose of determining their effect on the survival,
      phenotype and period of nynmphal development of this species. The dosage
      mortality line of regression was determined and the values of CE50 = 0.042% and
      CE95 = 0.357% were obtained. Sublethal effects were observed in the nymphs
      treated with the 4 tested concentrations whereas the morphogenetic effects in
      adult insects only occurred when they were exposed to higher concentrations
      (0.25% and 0.4%). The nymph development stage showed a highly significant
      increase when the diflubenzuron concentration was raised. (F = 11.64; p < 0.001).

PMID- 11826539
TI  - [Emerging viral diseases].
AB  - In the last few years an increasing rise of new infectious diseases or of other
      diseases considered to be under control has been observed. The so called emerging
      and reemerging diseases are those new infections that have come up in a
      population or those existing diseases which incidence and geographic extension
      are on a rapid increase. Factors such as social and economic situations, medical
      assistance, food production, changes in human behaviours, environmental changes,
      health systems deterioration, and adaptation and changes of microorganisms are
      related with the emergence or reemergence of a number of entities. This paper
      sets forth an analysis of the emergence and reemergence of viral diseases and of
      those factors that have had an impact on this situation.

PMID- 11826540
TI  - [Patterns of drug resistance in Staphylococcus aureus from human clinical
      isolates].
AB  - Fifty circulating strains of Staphylococcus aureus of clinical origin were
      characterized by their drug susceptibility to 15 antimicrobials through the
      method of radial diffusion in Mueller Hinton medium. Also, beta-lactam production
      was determined by acidimetric and chromogenic methods as well as the presence of
      methicillin-resistant strains. It was confirmed that 32% of strain was
      susceptible to tested antimicrobials, the most effective of which were imipenem,
      norfloxacyn, and amikacyn for 98, 96 and 92% susceptibility respectively. Twenty
      seven different drug resistance patterns were found in the studied strains. 22%
      of the total strains was beta-lactam producers whereas 27% of the latter turned
      out to be methicilline-resistant.

PMID- 11826541
TI  - [Hemorrhagic dengue in primary dengue].
AB  - We described the clinical and humoral development of a 7-years old boy who had
      hemorrhagic dengue in the dengue epidemic taken place in Santiago de Cuba in
      1997. During this stage, dengue was serologically confirmed in 77 patients under
      15 years of age but only one case was considered to be hemorrhagic dengue in
      spite of the fact that the patient had no history of this disease and that the
      virus had not been circulating in the country for over 15 years. The boy was
      under shock on the fourth day of the process, with hemoconcentration, pleural and
      ascitic effusions, thrombocytopenia and later a nosocomial sepsis, but he
      completely recovered in a period of 20 days.

PMID- 11826542
TI  - [Hair infestation by Phthirus pubis (Anoplura: Pediculidae)].
AB  - A case of lice infestation of the hair in a 24 year-old man was reported. After
      the entomological identification of adults and immature stages of the vector; it
      was confirmed that the only existing parasite was Phtihirus pubis Linnaeus 1758,
      a hematophagous insect that usually infests pubis, armpit, eyelids, and other
      parts of the body but is rarely found in the head.

PMID- 11826543
TI  - [A novel immunization schedule for obtaining anti-LPS Haemophilus influenzae type
      b antibodies].
AB  - A novel immunization schedule was tested to increase antibodies to Haemophilus
      influenzae type B in which a 0.5% formaldehyde-inactivated cellular antigen and a
      partially purified lipopolysacharid antigen obtained from a selective
      precipitation with organic solvents were combined as immunogens. High specificity
      and biological activity antibodies with titers up to 1:256 were obtained by
      counterinmunoelectrophoresis; they were purified through a selective
      precipitation with ammonium sulphate and an ion-exchange chromatography using a
      DEAE-Sapharose column. The method proposed in this paper facilitates the
      production of purified antibodies useful for the improvement of serological
      diagnosis and H. influenzae b strain serotyping techniques.

PMID- 11826544
TI  - [Ventricular tachyarrhythmias in patients without structural heart disease.
      Clinical and electrophysiologic characteristics of the tachyarrhythmias and long
      term results of catheter ablation].
AB  - PURPOSE OF THE STUDY: Ventricular tachyarrhythmias without structural heart
      disease (SHD) form a heterogeneous group of unknown mechanism and different
      clinical and electrophysiological behavior. Purpose of the study was to analyze
      clinical and electrophysiological characteristics of the arrhythmias, and
      immediate and long-term results of catheter ablation. PATIENTS: Nineteen
      consecutive patients without SHD (7 F) aged 44.5 +/- 14.1 (18-66) years had 23
      ablation procedures. Documented arrhythmias varied from incessant ventricular
      premature beats (1 patient) through paroxysmal nonsustained ventricular
      tachycardia (5 patients), incessant "repetitive" (non)sustained ventricular
      tachycardia (4 patients) to paroxysmal sustained ventricular tachycardia (9
      patients). METHOD: Patients underwent standard electrophysiological examination.
      Mapping of focal arrhythmias was guided by earliest endocardial and epicardial
      activation, pace-mapping or both. In 1 patient with reentry tachycardia, mapping
      was guided by late potential during sinus rhythm and low-voltage fractionated
      diastolic potential during the tachycardia. RESULTS: Catheter ablation was
      performed in 19 patients and 23 ablation procedures. Mean fluoroscopy time per
      procedure was 25.4 +/- 16.0 (7-65) minutes. The arrhythmia was targeted in the
      right ventricle in 13 patients, and in the left ventricle in 6 patients. All
      clinically significant ectopic activity was eliminated in 14 patients and
      significantly reduced in other 2 patients. Ablation procedure failed in 2
      patients. In 1 patient sustained monomorphic ventricular tachycardia originating
      in the epicardial aspect of outflow tract close to the left anterior descending
      artery was not ablated. During the long-term follow-up 19.2 +/- 10.9 (2-42)
      months 14 (73.7%) patients are free of targeted ectopic activity, symptoms, and
      antiarrhythmic drugs. Other 2 patients experienced significant reduction of
      ectopic activity and previously ineffective antiarrhythmic therapy could be
      reduced. Thus, the clinical benefit was enhanced to 16 (84.2%) patients.
      CONCLUSION: Ventricular tachyarrhythmias in patients without SHD form a
      heterogeneous group of different clinical and electrophysiological behavior and
      different pathophysiological mechanisms. Majority of the arrhythmias can be
      eliminated by focal catheter ablation with high efficacy and safety. Deep
      intramural and epicardial origin of the arrhythmic substrate is common reason for
      catheter ablation failure.

PMID- 11826545
TI  - [Personal experience with intra-arterial locoregional chemotherapy of liver
      metastases from colorectal carcinoma].
AB  - Locoregional chemotherapy is one of the possible ways of treatment of inoperable
      metastatic affection of the liver by colorectal carcinoma. The advantage of
      regional administration of the cytostatic is the possibility to achieve a higher
      local concentration of the cytostatic associated with a higher percentage of
      therapeutic responses. In our department we preferred combined locoregional
      intraarterial chemotherapy (5-fluorouracil/Mitmycin C/Doxorubicin) combined with
      systemic intravenous chemotherapy (5-fluorouracil/leukovirin). Locoregional
      cghemotherapy was administered in the majority as chemotherapy of series 2 or 3
      with a very good tolerance. In 2/19 patients we observed marked diminution of
      liver metastases and subsequent operability and with a duration of complete
      response for 13 and 18 months. In 7/19 patients a partial therapeutic response
      was achieved. The total therapeutic response (complete and partial) was 47%.
      Locoregional chemotherapy attains a higher therapeutic response as compared with
      systemic chemotherapy and is associated with an acceptable toxicity.

PMID- 11826547
TI  - [Adrenal gland incidentaloma].
AB  - Adrenal incidentaloma is an incidentally detected formation on examination of
      another cause such as visualization of the adrenal glands. From 1996 till
      December 1999 in the Endocrinological Institute in Lubochna 60 patients with
      adrenal incidentaloma were examined. In 75% afunctional tumours were involved. In
      16.6% (10 patients) the authors recorded an initial impairment of cortisol
      secretion, in 3.2% (2 patients) impaired aldosterone secretion, similarly in 3.2%
      (2 patients) a pheochromocytoma and in one patient (1.6%) impaired secretion of
      17-hydroxyprogesterone. Functionally active incidentalomas accounted for one
      quarter of the investigated group.

PMID- 11826546
TI  - [Effectiveness and tolerance of fosinopril in the treatment of arterial
      hypertension of mild and medium severity].
AB  - BACKGROUND: The standard of hypertension control in the population is not
      satisfactory, only 20% patients with hypertension achieve target values of blood
      pressure (BP). Extensive prospective studies revealed that diuretics, beta
      blockers as well as the majority of calcium channel blockers and ACE inhibitors
      can significantly reduce the incidence of complications of hypertension and are
      therefore considered drugs of first choice in the treatment of hypertension. The
      additive effects of ACE inhibitors are manifested in particular after larger
      doses. OBJECTIVE OF TRIAL: To assess the effectiveness and tolerance of the
      modern long-acting ACE inhibitor--fosinopril--in the treatment of mild and medium
      severe hypertension and its effect on some anthropometric and laboratory
      parameters. RESULTS: Fosinopril as monotherapy in amounts of 10, 20 and 40 mg led
      to normalization of BP in 85% of the group (n = 203) and was very well tolerated.
      Only 11% of the group needed a combination with hydrochlorothiazide--12.5 g/day-
      after which normal BP levels were attained. Only 4% of the patients did not
      complete the study on account of undesirable effects, incl. 3 patients where
      cough was the reason for discontinuation. After 12 weeks treatment the systolic
      BP was reduced on average by 31 mm Hg and the diastolic BP by 16 mm Hg. The heart
      rate (HR) declined on average by 3 beats/min. (p 0.001). After four weeks
      treatment a significant decline of the blood sugar level occurred which was even
      more marked after 12 weeks of treatment (on average by 0.27 mmol/l and at the
      same time a significant drop of sodium occurred (by 2 mmol/l), of total and LDL
      cholesterol (by 0.26 and 0.23 mmol/l). An expected increase of the potassium
      level occurred (by 0.1 mmol/l) and creatinine (by 3.4 mumol/l in plasma).
      CONCLUSION: Fosinopril treatment with 10-40 mg/day was effective in monotherapy
      of hypertension in 85% patients and was well tolerated. After 12 weeks treatment
      a significant decline of the BP, HR occurred as well as the expected decline of
      the plasma Na/K ratio and improvement of some metabolic parameters.

PMID- 11826548
TI  - [Changes in serum levels of IGF-I and its binding proteins and their relation to
      microcirculation in obese patients].
AB  - The IGF-I system and its binding proteins participate in the pathogenesis of
      vascular affections under various pathological conditions. The mechanism and mode
      of its action were however not elucidated in details so far and views on its role
      are controversial. The objective of the study was to assess the relationship of
      this system and the blood flow in the microcirculation in obese patients. The
      authors examined 21 obese patients (BMI 39.7 +/- 7.3 kg/m2) and a group of
      healthy volunteers. They examined: serum concentrations of total IGF-I, free IGF
      I, IGFBP-1,-2,-3, and -6, total cholesterol, HDL-cholesterol, LDL-cholesterol and
      triglycerides as well as the intimomedial thickness of the common carotid
      arteries and parameters of blood flow in the microcirculation, evaluated by a
      laser-Doppler examination. In obese patients there were significantly lower serum
      concentrations of IGF-I and free-IGF I (p < 0.05) as compared with the control
      group. Comparison of the function of the microcirculation revealed in obese
      patients, as compared with the control group, a lower percentage increase of
      perfusion after occlusion (PORH%, p < 0.05) and after heating (TH%, p < 0.05) and
      a slower onset of thermal hyperaemia (THmax/t, p < 0.05). In the control group
      serum concentrations of free-IGF-I correlated inversely with the maximum
      perfusion after heat induced hyperaemia (THmax (r = -0.54, p < 0.02) and the rate
      of onset of hyperaemia after heating (THmax/t) (r = 0.51, p < 0.02). In the group
      of obese patients serum concentrations of free-IGF-I correlated inversely with
      the maximum perfusion after heat induced hyperaemia (THmax) (r = -0.55, p <
      0.02), and IGFBP-3 concentrations correlated inversely with maximum hyperaemia
      after occlusion (PORGmax) (r = -0.57, p < 0.01). The results suggest that the
      function of the microcirculation in obese subjects is affected. The activity of
      the IGF-I system and its binding proteins is related to the affected function of
      the microcirculation and a negative part is played particularly by serum
      concentrations of free IGF-I. The negative effect of IGFBP-3 on the function of
      the microcirculation is surprising.

PMID- 11826549
TI  - [Chlamydia pneumoniae and myocardial infarct? (Serologic study)].
AB  - At disposal for tests were 156 blood sera collected from patients with acute
      myocardial infarction (AMI samples) and 67 blood sera collected from control
      persons. The sera were tested by the following reactions: complement fixation
      test (CFT) with genus-specific antigen (C. psittaci, Bioveta, Ivanovice na Hane),
      ELISA in the immunoglobulin classes IgG and IgA using the MOMP (Vircell, Spain)
      and LPS (MEDAC, Hamburg, BRD) Chlamydia pneumoniae (C. p.) antigens, and indirect
      immunofluorescence test with MOMP C. p. antigen (MRL Diagnostics, USA). Eight AMI
      samples were not tested by CFT owing to haemolyis or lipaemia. CFT titres ranging
      from 1:4 to 1:16 were found in 28 of the 148 AMI samples (18.9%) and 3 of the 67
      control samples (4.5%). The between-group difference was highly significant (chi
      2 = 7.795 at 0.01). Positive by rELISA anti LPS C. p. were 89 of the 155 AMI
      samples (57%) and 22 of the 62 control samples (35%). Also this difference was
      highly significant (chi 2 = 8.528; alpha = 1%). The following conclusions can be
      drawn from the results: 1. Chlamydia pneumoniae can play an important role in the
      aetiology of atherosclerosis leading to AMI. 2. rELISA anti-LPS can be
      recommended for routine serological diagnostics of C. pneumoniae and studies of
      its role in the aetiology of atherosclerosis. 3. The complement fixation test is
      still suitable for the screening of human chlamydiosis.

PMID- 11826550
TI  - [Ambulatory blood pressure monitoring in a young population].
AB  - Ambulatory twenty four hour blood pressure monitoring (ABPM) is an exact method,
      enabling by repeated measurements to create blood pressure profile, which shows a
      close correlation with end organ damage. Normal values were taken from clinical
      trials, where the mean age of probands was highly above 30 years. The aim of this
      trial was to determine mean values for ABPM in population aged 18-30 years and to
      create "normal values" for this population. We have examined 162 probands. The
      mean office blood pressure was 128.18 +/- 11.2/82.91 +/- 8.29 mm Hg, the mean
      ABPM (24 hours) was 118.51 +/- 9.11/70.59 +/- 6.30 mm Hg. Systolic, mean and
      pulse pressure was significantly higher in males. Systolic and pulse blood
      pressure showed a close correlation with height, weight, waist and waist/hip
      ratio (r = 0.40-0.47). The upper value of 24 hour BP in young population is
      between 125/75 mm Hg and 130/80 mm Hg according to our results.

PMID- 11826552
TI  - [Hypertension and cerebrovascular strokes].
AB  - Cerebrovascular attacks are worldwide one of the main causes of death and
      invalidity. The incidence rises exponentially with age. Hypertension is the main
      risk factor which increases the risk of cerebrovascular attacks as much as four
      times. Treatment of hypertension reduces the incidence of all types of
      cerebrovascular attacks. The author discusses different types of cerebrovascular
      attacks, primary and secondary prevention with emphasis on possible influencing
      of high blood pressure.

PMID- 11826551
TI  - [Absence of a decrease in nocturnal arterial pressure as an independent
      prognostic factor in hypertension].
AB  - Considerable evidence has accumulated indicating that the lack of the normal
      nocturnal fall in blood pressure (non-dipper) may represent an important
      prognostic factor in hypertension. This review focuses on clinical studies
      showing close association between a non-dipper pattern of blood pressure and
      cardiovascular events such as glomerular capillary hypertension, cerebrovascular
      events, left ventricular hypertrophy and ventricular arrhythmias. A close
      relationship between impairment of the circadian rhythm of blood pressure and
      that of natriuresis is described. The therapeutic profit from the knowledge that
      a given patient is a non-dipper and/or salt-sensitive is illustrated.

PMID- 11826553
TI  - [Extravascular lung water in acute respiratory distress syndrome:
      pathophysiology, monitoring and therapeutic possibilities].
AB  - Excessive amount of extravascular lung water (EVLW) resulting from increased
      permeability of alveolo-capillary membrane is a pathophysiological hallmark of
      acute respiratory distress syndrome (ARDS). Increased EVLW produces hypoxemia by
      interference with gas exchange. During shock resuscitation, in disorders in which
      microvascular endothelial integrity is impaired, large volumes of intravenous
      fluids needed to restore tissue perfusion may also be associated with the risk of
      increased accumulation of EVLW. The presented paper briefly reviews the
      mechanisms involved in lung edema formation and describes current options to
      measure EVLW. In addition, it discusses clinical implications of EVLW measurement
      in intensive care setting with particular focus on transpulmonary indicator
      dilution technique.

PMID- 11826554
TI  - [Treatment of paroxysmal nocturnal hemoglobinuria (PNH)].
AB  - Paroxysmal nocturnal hemoglobinuria is an acquired clonal disorder of the
      hematopoietic stem cell in which intravascular hemolysis is due to an intrinsic
      defect in the membrane of red cells that makes them increasingly susceptible to
      lysis by complement. The phenotypic hallmark of PNH cells is an absence or marked
      deficiency of GPI-anchored proteins such as CD 59+, CD 55+ and others which
      normally protect cells from the action of complement. PHN is closely associated
      with aplastic anemia. Some degree of bone marrow failure is always present.
      Management of PNH is complicated by a highly variable clinical picture and
      course. Some patients have severe anemia aggravated by hemolytic crises and
      associated thromboses. Bone marrow failure is accompanied with frequent
      infections and hemorrhagic manifestations due to thrombocytopenia. With the
      exception of marrow transplantation, no definite therapy is available. In the
      exceptional circumstance in which the patient has a syngeneic twin, bone marrow
      transplantation is the most appropriate therapy for severe PNH because of absence
      of graft-versus-host disease. In general syngeneic transplantation without
      preconditioning has been unsuccessful because abnormal hematopoiesis returns.
      Allogeneic bone marrow transplantation has been used, but the transplant
      associated morbidity and mortality are high due mainly to the fatal graft-versus
      host disease and severe posttransplant marrow failure. Use of an unrelated donor
      transplant has to be considered as contraindicated. PNH is associated with
      striking predisposition to intravascular thrombosis which often involves the
      portal system or the brain. Fatal thromboses account for about 40-50% of all
      deaths in patients with PNH. The etiology of the thrombophilia in PNH is not
      fully clarified. Anticoagulation or thrombolytic therapy is required for
      treatment of venous thrombosis, the latter vena cava. Prophylactic
      anticoagulation in patients without contraindications such as severe
      thrombocytopenia seems to be justified. However, whether such therapy may be
      efficacious in reducing the incidence of thromboses or affect survival is
      conjectural. PNH patients have varying degree of platelet activation and some
      authors suggest that antiplatelet therapy might be efficacious in reducing the
      incidence and severity of venous thrombosis in PNH. Pregnancy is hazardous.
      Female patients should avoid the use of oral contraceptives. Pregnant patients
      require combined care of an experienced hematologist and obstetrician specialized
      in the management of high-risk pregnancies.

PMID- 11826555
TI  - [Aspects of treatment of hypertrophic obstructive cardiomyopathy with emphasis on
      the role of percutaneous transluminal ablation of the myocardial septum].
AB  - The prevalence of hypertrophic cardiomyopathy is approximately 0.2% whereby the
      obstructive form accounts for one quarter. The basic treatment involves
      administration of negatively inotropic drugs (beta-blockers and/or verapamil),
      which reduce the intraventricular pressure gradient and have a positive impact on
      the symptomatology. In patients refractory or intolerant to medicamentous
      treatment surgical or catheterization is used. Percutaneous transluminal septal
      myocardial ablation reduces significantly the symptomatology of dyspnoea and
      stenocardia, increases load tolerance and improves the left ventricular diastolic
      function. In none of the mentioned therapeutic approaches so far a favourable
      effect on the prognosis of patients with a risk profile associated with
      hypertrophic obstructivel cardiomyopathy was proved.

PMID- 11826556
TI  - [An unusually long survival after surgery in post-infarct rupture of the
      interventricular septum and resection of a left ventricular aneurysm].
AB  - In the submitted case-history the author describes a patient who 15 years
      previously underwent after an extensive myocardial infarction with rupture of the
      interventricular septum and a left ventricular aneurysm a plastic operation of
      the interventricular rupture and aneurysmectomy. This man, at present 70 years
      old, lives without any significant restrictions. The author advocates an active,
      intensive and aggressive diagnostic and therapeutic approach in all thus vitally
      threatened patients for whom this arsenal offers a much greater hope for
      extension and improvement of life than the classical conservative therapy.

PMID- 11826557
TI  - Nevada law aims to halt drug diversion by wholesalers.

PMID- 11826558
TI  - FDA to develop rules for mandatory bar-code labels.

PMID- 11826559
TI  - Miami hospital joins Florida's disease management program.

PMID- 11826560
TI  - Frovatriptan approved as migraine treatment.

PMID- 11826561
TI  - Oregon, U.S. attorney general clash on physician-assisted suicide.

PMID- 11826562
TI  - CMS starts nursing-home quality-performance reporting project.

PMID- 11826563
TI  - Study finds most psychotropic drug use in nursing homes meets federal guidelines.

PMID- 11826564
TI  - NSAIDs may prevent Alzheimer's disease, study finds.

PMID- 11826565
TI  - Defining a learning community.

PMID- 11826566
TI  - Esomeprazole magnesium.

PMID- 11826567
TI  - Projecting future drug expenditures--2002.
AB  - Drug-cost projections for 2002 and factors likely to influence drug costs are
      discussed. The United States continues to face the challenge of increased growth
      in health expenditures, and pharmaceutical expenditures continue to increase
      significantly faster than the growth in total health care expenditures. These
      increases can be largely attributed to a combination of general inflation, an
      increase in the average age of the U.S. population, and the increased use of new
      technologies. On the basis of price inflation and nonprice inflationary factors,
      including increases in volume, shifts in patient and therapeutic intensity, and
      the expected approval of new drugs, we forecast a 15.5% increase in drug
      expenditures in 2002 for hospitals and clinics and an 18.5% increase for
      ambulatory care settings. One of the most substantial contributors to the rise in
      pharmaceutical expenditures over the past decade is the successful introduction
      and rapid diffusion of new pharmaceuticals. Data about many new drugs on the
      horizon are provided. One agent likely to have the highest impact on hospitals in
      the next year is drotrecogin alfa for the treatment of sepsis. The cost of this
      agent is expected to range from $3,000 to $10,000 per patient per course of
      therapy. Other factors influencing medication costs, including generic
      medications, legislative initiatives, and the recent acts of terrorism committed
      against the United States, are also discussed. Technological, demographic, and
      market-based changes, and possibly public policy changes, will have a dramatic
      influence on pharmaceutical expenditures in the coming year. An understanding of
      what is driving the changes is critical to the effective management of these
      resources.

PMID- 11826568
TI  - Developing a drug-cost model for a capitated patient population in an integrated
      health care system.

PMID- 11826569
TI  - Sedation, analgesia, and neuromuscular blockade of the critically ill adult:
      revised clinical practice guidelines for 2002.

PMID- 11826571
TI  - Clinical practice guidelines for sustained neuromuscular blockade in the adult
      critically ill patient.

PMID- 11826570
TI  - Clinical practice guidelines for the sustained use of sedatives and analgesics in
      the critically ill adult.

PMID- 11826573
TI  - Policy on alternative therapies.

PMID- 11826572
TI  - Vancomycin concentrations associated with red-top and serum-separator collection.

PMID- 11826574
TI  - Secretin available under FDA treatment protocol.

PMID- 11826575
TI  - [Prospective study of patients with hepatitis C virus with persistently normal
      transaminases].

PMID- 11826576
TI  - [Association of D-dimer and helicoidal thoracic scanner for diagnosis of
      pulmonary embolism. Prospective study of 106 ambulatory patients].
AB  - OBJECTIVE: Ventilation/perfusion pulmonary scintigraphy (PS), the current
      mainspring in the diagnosis of pulmonary oedema (PE), is frequently non
      conclusive. The objective of this study was to determine, prospectively, the
      diagnostic value of the association of D-dimers and helicoidal thoracic scanner
      (HTS) in a continuous series of ambulatory adults with suspected PE and admitted
      to a cardiologic emergency unit. METHODS: Exclusion criteria were as follows:
      symptoms or clinical signs of seventy, contraindication for HTS and/or on
      pulmonary angiography, curative anticoagulant therapy for more than 48 hours,
      history of PE less than 3 months before or the impossibility of conducting all
      the examinations with 48 hours. All the patients underwent determination of D
      dimers by rapid ELISA test, HTS and 2 reference examinations, venous Doppler of
      the lower limbs and a PS, completed by pulmonary angiography if the PS did not
      permit diagnosis and the venous Doppler was negative. RESULTS: One hundred and
      six patients were selected over a recruitment period of 18 months. The prevalence
      of PE was of 45% (48/106). Forty-four of the 48 PE of the series were central
      form. HTS was considered dubious in 10 patients (10.4%, PE+ n = 2, PE- n = 8).
      The results of D-dimers were negative in only 34.5% patients without PE (20/58).
      Pulmonary angiography was necessary in 15 patients. The negative and positive
      predictive values of D-dimers were respectively of 100 and 55.8% (48/86) and
      those of HTS respectively 100 (46/46) and 92% (46/50). CONCLUSION: The diagnostic
      strategy of clinical suspicion of PE, starting with determination of D-dimers by
      rapid ELISA test followed by helicoidal thoracic scanner in the case of a
      positive result, was particularly effective in this series of patients with a
      high prevalence of PE. These results must be confirmed in a larger series and in
      a general emergency unit.

PMID- 11826577
TI  - [Pregnancy in patients with Behcet's disease].
AB  - INTRODUCTION: Behcet's disease is particularly frequent in the Mediterranean
      countries and in the Far East. Its predominance in men is the reason why its
      association with pregnancy has rarely been reported in the literature.
      OBSERVATIONS: Three pregnancies occurred in two patients with Behcet's disease.
      In the first case the disease was diagnosed post partum. The second pregnancy in
      a stabilized patient was complicated by depression and abortion at 16 weeks of
      amenorrhea. The second patient presented with an articular episode after
      delivery, requiring an increase in dose of corticosteroids. COMMENTS: The
      interventions between pregnancy and Behcet's disease are obscure. The progression
      of the disease varies from one women to another and from one pregnancy to the
      next in the same woman. The observations reported here add to those describing
      aggravation of Behcet's disease during or after pregnancy.

PMID- 11826578
TI  - [Salmonella enteritidis splenic abscess complicating a Plasmodium falciparum
      malaria attack].
AB  - INTRODUCTION: Salmonella splenic abscesses are rare and usually occur on pre
      existing lesions. OBSERVATION: A Moorish 16 year-old woman from Senegal presented
      with a S. enteritidis abscess without any factor other than an attack of P.
      falciparum malaria. Treatment associated quinine salts, antibiotherapy and
      splenectomy. COMMENTS: P. falciparum malaria attacks not only induce humoral and
      then cellular immunodepression but are also at the origin of infarction or
      splenic hematoma that may enhance bacterial infection and the development of
      abscesses. Splenectomy or percutaneous drainage associated with antibiotherapy is
      the usual treatment for splenic abscesses. Prognosis remains severe (13 to 16%
      mortality).

PMID- 11826579
TI  - [Antiphospholipid syndrome in husband and wife and multiple sclerosis in the
      daughter].

PMID- 11826581
TI  - [Cerebrospinal meningitis with atypical onset].

PMID- 11826580
TI  - [Pyomyositis with acute kidney failure in immunocompetent patient].

PMID- 11826582
TI  - [Eosinophilic pancreatitis].

PMID- 11826583
TI  - [Blood culture update].
AB  - BACKGROUND: Blood culture is one of the most important bacteriological
      examinations with important clinical and therapeutic consequences. Blood cultures
      should be ordered in all patients with signs suggesting septicemia, endocarditis
      or severe infection (pneumococcal pneumonia, bacterial meningitis with
      bloodstream dissemination). Blood culture methods have evolved considerably over
      the last twenty years. After using manual methods for many years, read by non
      standardized visual methods, the development of media with defined compositions
      and supplemented to allow growth of bacteria difficult to culture has been
      associated with the development of automatic blood culture devices. AUTOMATIC
      DEVICES: These devices have undergone rapid improvement. Semi-automatic devices
      (Bactec NR-660) were rapidly followed by completely automatic techniques,
      including four devices currently available: since 1989 Bio-Argos (Rio-Rad) and
      Bact/Alert (Organon-Teknika) and in 1993, Bactec 9240 (Becton-Dickinson) and
      Vital (BioMerieux). All these devices allow automatic detection of CO2 produced
      during bacterial growth. Automatic reading systems provide continuous output
      avoiding the need for invasive methods and thus the risk of contamination in
      addition to saving time. Potential application to achieve quantitative blood
      cultures for intensive care units is in the development stage. CONSEQUENCES: The
      reliability of these devices is well recognized and their contribution to severe
      bacterial infection is undeniable. There are certain limitations however related
      to material cost and the non-identification of the pathogen involved. Molecular
      biology techniques open new perspectives in this field. The evolution of
      techniques, definitions, and pathogenic approach to septicemia must be revisited
      as new infectious situations have been identified at the same time as new
      investigation tools resulting from considerable technological progress. New
      methods of blood culture have largely contributed to this progress.

PMID- 11826584
TI  - [The Gulf war syndrome].
AB  - SPARSE DATA: The Gulf war syndrome remains a little know entity since its first
      appearance 10 years ago. The objective of our work was to synthesize the data
      published on the subject in the scientific literature. We analysed the results of
      American and English epidemiological surveys, from which it was difficult to
      distinguish the existence of a univocal syndrome. IMPRECISE DEFINITION: It is
      difficult to give a clear clinical definition of the syndrome, the signs of which
      fluctuate depending on the studies. Chronic fatigue is frequently associated with
      the Gulf war syndrome, although some studies have described electrophysiological
      neurological lesions. NUMEROUS HYPOTHESES: The role of stress, vaccinations and
      their adjuvants, exposition to neurotoxic substances and weak uranium have been
      incriminated. We propose that multiple factors be integrated in the research for
      the genesis of this atypic syndrome.

PMID- 11826585
TI  - [Future molecules in heart failure].
AB  - TODAY: The management of heart failure (HF) has considerably progressed over the
      last two decades. Treatment today relies on prevention and treatment of
      congestion (limited salt intake, diuretics, converting enzyme inhibitors) and
      limiting neurohormone stimulation (converting enzyme inhibitors +/- aldactone,
      beta-blockers). IN THE YEARS TO COME: Based on new concepts, several therapeutic
      strategies are interesting: blocking over vasoconstrictor systems which have not
      been taking into account; stimulation of vasodilator and natriuretic systems;
      modulation of cardiac remodelling; modulation of the immune and inflammatory
      systems; modification in intrinsic contractility; prevention of rhythm disorders.
      Among these differing strategies and molecules, it is not easy to predict those
      that will change the HF prognosis. In any event, their efficacy and safety remain
      to be demonstrated with large cohort randomised studies. THE PRINCIPLES: To
      reduce the number of drugs administered, two options appear particularly
      interesting: measurement of hormone levels (BNP) in order to adjust treatment and
      administration of molecules with greatest efficacy and safety profiles; limit
      cardiac remodelling by using new imaging techniques to detect it more precisely
      and select the molecule(s) exerting the required effect. To target the new
      molecules better, patients should be classified according to their etiology,
      stage and progressive profile of their disease, cardiac remodelling, expression
      of principle endocrine systems and pro-inflammatory cytokines, expression of
      inflammatory and immune systems and inherent genetic characteristics and response
      to treatment. This would permit the adaptation of treatment to each individual
      patient with heart failure.

PMID- 11826586
TI  - [Total hip prosthesis, is it a criterion for the assessment of structural
      modulator efficiency?].
AB  - OBJECTIVE: It has been evaluated during a longitudinal prospective study
      (ECHODIAH study) conducted over a 3-year period estimated the pertinence of total
      hip arthroplasty as an assessment criterion for the evaluation of the efficacy of
      structuromodulators. RESULTS: It is clear that patients who undergo total hip
      arthroplasty have more advanced hip disease. Factors predisposing to total hip
      arthroplasty have been demonstrated by multivariate analysis: advanced age,
      female gender, severe pain, Lequesne index, superolateral migration of the
      femoral head, important structural alterations. Other factors such as area of
      residence were not found to have any influence. Consequently, total hip
      arthroplasty appears to be a valid and reliable assessment criteria for
      degenerative hip disease.

PMID- 11826587
TI  - [When should the implantation of total hip prosthesis be considered in patients
      with coxarthrosis?].
AB  - COMPOSITE SCORE: The decision to perform total hip arthroplasty in patients with
      degenerative hip disease requires a homogeneous set of indications to determine
      as objectively as possible patient needs and priorities and to help the physician
      to indicate surgery appropriately. A NEW SCORING SYSTEM: To date, the different
      scores proposed have not taken into account the severity of the structural
      involvement nor the use of symptomatic treatments. A new composite score was thus
      developed using symptomatic, structural and therapeutic variables for
      osteoarthritis and its impact on quality of life. Cut-off value: A score of 40 is
      used as the cut-off value for indication of total hip arthroplasty with a
      sensitivity and specificity greater than 80%. Using values > or = 40, total hip
      arthroplasty is predictable in 54.3% of the patients.

PMID- 11826588
TI  - [Functional re-education, self-education, and education of patients with leg
      arthrosis].
AB  - EXPERT OPINIONS: Functional rehabilitation, self-rehabilitation in the patient's
      home and patient education are the basis of non-drug management of patients with
      osteoarthritis. This approach helps reduce pain and the frequency of
      consultations, and improves physical activity and quality of life. FUNCTIONAL
      REHABILITATION: The objective is to limit pain, to maintain joint mobility and
      muscle force, and to learn how to manage one's disease. Evidence in the
      literature demonstrates the efficacy of functional rehabilitation. SELF
      REHABILITATION: The objective of self-rehabilitation is the same as functional
      rehabilitation and data in the literature indicate positive results on pain and
      functional symptoms. PATIENT EDUCATION PROGRAMS: Presented in the form of advise
      booklet or videos (CD-Room Arthemus), patient education programs improve non-drug
      management of osteoarthritis. COMPLEMENTARITY: It is logical to associate the
      different modalities of non-drug management of osteoarthritis since their
      objectives are complementary and synergetic.

PMID- 11826589
TI  - [Impact assessment of arthrosis education programs].
AB  - TWO COMPLEMENTARY APPROACHES: Education programs are an integral part of the
      treatment of osteoarthritis and should include information of prognosis as well
      as advise on lifestyle and/or use of antalgesics. They should also constitute a
      structured educational approach with the objective of reaching a certain level of
      comprehension. EVALUATION: The efficacy of educational programs is difficult to
      demonstrate. However, results of recent evaluations based on the best
      methodological criteria should be helpful in defining optimal methods for patient
      education.

PMID- 11826590
TI  - [Current medical possibilities in the treatment of arthrosis].
AB  - DRUG CLASSES: Three drug classes can be distinguished. The first includes drugs
      used for symptomatic care. This class includes a subclass of rapid action drugs
      (antalgesics, nonsteroidal antiinflammatory drugs, NSAID) and a subclass of
      symptomatic slow acting drugs. The second class corresponds to antiosteoartritis
      drugs called chondroprotective drugs or structure modifying. The third class
      includes drugs used for local care. TREATMENT STRATEGY: For episodes of acute
      pain, the first intention prescription should include rapid action drugs for
      symptomatic relief (paracetamol then NSAID). A symptomatic slow acting
      antiosteoarthritis drug can also be associated then continued after interrupting
      the rapid action symptomatic drugs. Diacerein is a drug with prolonged
      antiosteoarthritis action that has proven efficacy for symptom relief equi-valent
      to NSAID assessed in terms of pain relief and function: the ECHODIAH study
      provides arguments favoring its chondromodulating effect.

PMID- 11826591
TI  - [Results of the ECHODIAH clinical trial on hip arthrosis].
AB  - STUDY OBJECTIVE: The principal objective of ECHODIAH study conducted in patients
      with hip osteoarthritis was to evaluate the chondroprotective effect of potential
      of diacerein compared with placebo. The study was conducted over a 3-year period
      using progression of joint space narrowing as the assessment criterion. RESULTS:
      For aggravation, expressed as joint space narrowing of at least 0.5 mm, there
      were significantly fewer patients in the diacerein group than in the placebo
      group; aggravation came significantly later in the diacerhein group. In the
      population of patients who completed at least 3 months treatment, the sparing
      effect on joint space narrowing was 32% in the diacerhein group compared with the
      placebo group. In addition, the mean progression of joint space narrowing was
      significantly less in patients treated with diacerein; the mean progression
      decreased from 0.18 mm/year at the end of the first year to 0.13 mm/year at the
      end of the third year.

PMID- 11826592
TI  - The nature of microemboli in patients with artificial heart valves.
AB  - Cognitive decline has recently been found to be associated with microemboli in
      cerebral vessels in patients with artificial heart valves. The authors sought to
      determine the nature of such microemboli, that is, whether they are gaseous or
      solid, by comparing their characteristics to those of artificially generated air
      emboli in patients with patent foramen ovale (PFO). Three hundred and forty-eight
      microemboli were recorded in 11 patients with artificial valves (all taking
      coumadin), and 86 microemboli were recorded in response to intravenous injection
      of saline agitated with air in 8 PFO patients. No difference in intensity,
      duration, or relative velocity of microemboli was found between groups. The
      authors conclude that microemboli generated from artificial heart valves are
      generally gaseous and not solid.

PMID- 11826593
TI  - Transcranial duplex imaging with a sulfurhexafluoride echocontrast agent:
      enhancement and diagnostic quality.
AB  - BACKGROUND AND PURPOSE: The authors investigate characteristics of ultrasound
      enhancement and diagnostic quality of a sulfurhexafluorides (SF6)-containing
      echocontrast agent (SonoVue) in cerebrovascular patients with insufficient
      temporal bone window by transcranial color-coded duplex (TCCD) sonography.
      METHODS: Thirty patients (mean age = 62.2 +/- 11.1 years) were enrolled. SF6 was
      administered intravenously in 4 different doses (0.3, 0.6, 1.2, and 2.4 mL). By
      videotape analysis, time to contrast appearance, duration of contrast
      enhancement, and duration of clinically useful signal enhancement were measured.
      Overall quality of ultrasound investigation was also assessed. RESULTS: Time to
      contrast appearance ranged from 11 to 74 seconds (mean = 26 seconds). For the
      0.3, 0.6, 1.2, and 2.4 mL doses, average times to contrast appearance of 30 +/-
      12 seconds, 28 +/- 10 seconds, 23 +/- 8 seconds, and 22 +/- 6 seconds were
      measured. Duration of TCCD signal enhancement was 438 +/- 169 seconds, 483 +/-
      195 seconds, 713 +/- 299 seconds, and 788 +/- 344 seconds for the different
      doses. Clinically useful enhancement was 160 +/- 124 seconds, 200 +/- 157
      seconds, 260 +/- 166 seconds, and 327 +/- 239 seconds. CONCLUSIONS:
      Administration of SonoVue led to a quality improvement in 21 patients. In TCCD,
      it optimizes visualization of the cerebral arteries in patients with inadequate
      bone window. A dose of at least 1.2 mL provides the best enhanced images.

PMID- 11826594
TI  - Three-dimensional intraoperative ultrasound of vascular malformations and
      supratentorial tumors.
AB  - The benefits and limits of a magnetic sensor-based 3-dimensional (3D)
      intraoperative ultrasound technique during surgery of vascular malformations and
      supratentorial tumors were evaluated. Twenty patients with 11 vascular
      malformations and 9 supratentorial tumors undergoing microsurgical resection or
      clipping were investigated with an interactive magnetic sensor data acquisition
      system allowing freehand scanning. An ultrasound probe with a mounted sensor was
      used after craniotomies to localize lesions, outline tumors or malformation
      margins, and identify supplying vessels. A 3D data set was obtained allowing
      reformation of multiple slices in all 3 planes and comparison to 2-dimensional
      (2D) intraoperative ultrasound images. Off-line gray-scale segmentation analysis
      allowed differentiation between tissue with different echogenicities. Color-coded
      information about blood flow was extracted from the images with a reconstruction
      algorithm. This allowed photorealistic surface displays of perfused tissue,
      tumor, and surrounding vessels. Three-dimensional intraoperative ultrasound data
      acquisition was obtained within 5 minutes. Off-line analysis and reconstruction
      time depends on the type of imaging display and can take up to 30 minutes. The
      spatial relation between aneurysm sac and surrounding vessels or the skull base
      could be enhanced in 3 out of 6 aneurysms with 3D intraoperative ultrasound.
      Perforating arteries were visible in 3 cases only by using 3D imaging. 3D
      ultrasound provides a promising imaging technique, offering the neurosurgeon an
      intraoperative spatial orientation of the lesion and its vascular relationships.
      Thereby, it may improve safety of surgery and understanding of 2D ultrasound
      images.

PMID- 11826595
TI  - Harmonic imaging of the brain parenchyma in a dog model following NC100100
      (Sonazoid) bolus injection.
AB  - BACKGROUND AND PURPOSE: NC100100 (Sonazoid) is a new perfluorocarbon-based
      ultrasound contrast agent (UCA) that has not been introduced to transcranial
      harmonic imaging. METHODS: In an animal study on 6 beagle dogs, the authors
      performed harmonic power Doppler and gray-scale imaging (SONOS 5500, S4 probe)
      after bolus injection of 2 different doses of Sonazoid. Time intensity curves for
      brain parenchyma, masticatory muscle, and contralateral skull were generated, and
      the peak increase from baseline was computed. RESULTS: With harmonic gray-scale
      imaging, a dose-dependent homogeneous increase in acoustic intensity of the brain
      parenchyma was observed. Evaluation of the contralateral base of the skull showed
      a moderate signal decrease. In harmonic power Doppler sonography, signal increase
      was dose dependent also, but the signal pattern was inhomogeneous, with stronger
      enhancement in the anterior part of the brain. CONCLUSION: The new UCA Sonazoid
      is suitable for displaying brain perfusion. As already observed for other UCAs,
      gray-scale harmonic imaging with Sonazoid leads to a more homogeneous contrast
      increase in cerebral parenchyma compared to harmonic power Doppler imaging.
      Sonazoid produces a moderate shadowing effect, with signal attenuation in the
      underlying deeper regions of interest.

PMID- 11826596
TI  - The role of neuroimaging in headache.
AB  - Headaches are a universal experience and one of the most common causes for
      physician consultation. The physician must determine whether a neuroimaging study
      is warranted to aid in the diagnosis of primary or secondary headaches.
      Guidelines on neuroimaging of headache patients have been developed based on
      review of the literature; however, their applicability must be adapted to
      specific clinical situations. In general, neuroimaging is most likely to be
      useful if the history is not typical of a primary headache type (e.g., tension
      type, migraine, cluster headaches) or the neurological examination is abnormal.
      Neuroimaging has been crucial in the investigation of the pathogenesis of
      migraine and cluster headaches. Secondary headaches, which may be diagnosed by
      neuroimaging studies, include subarachnoid hemorrhage, cerebral venous
      thrombosis, cerebral autosomal dominant arteriopathy with subcortical infarcts
      and leukoencephalopathy, aqueductal stenosis, and arterial dissection.

PMID- 11826597
TI  - Ophthalmic artery flow direction on color flow duplex imaging is highly specific
      for severe carotid stenosis.
AB  - BACKGROUND/PURPOSE: Collateral flow patterns are important risk factors for brain
      ischemia in the presence of internal carotid artery (ICA) stenosis or occlusion.
      Ophthalmic artery (OA) flow reversal, routinely studied by transcranial Doppler
      sonography, is an important marker for high-grade ICA stenosis or occlusion. The
      authors sought to define the value of assessing OA flow direction with color flow
      duplex ultrasonography (CDUS) in the setting of significant ICA disease. METHODS:
      Of all patients having routine carotid ultrasound in the neurosonology laboratory
      between July 1995 and November 2000, 152 had both carotid and orbital (OA flow
      direction by reduced power orbital CDUS) examinations as well as angiographic
      confirmation of stenosis to which North American Symptomatic Carotid
      Endarterectomy Trial criteria could be applied. Degree of angiographic stenosis
      in these 152 patients (304 arteries) was correlated with OA flow direction.
      RESULTS: Of 304 arteries, 101 had greater than 80% stenosis by angiogram. In 56
      of these 101 arteries with high-grade stenosis or occlusion, the ipsilateral OA
      was reversed; however, OA flow direction was never reversed ipsilateral to
      arteries with less than 80% stenosis (sensitivity 55%, specificity 100%, negative
      predictive value 82%, and positive predictive value 100% for OA flow reversal as
      a marker of high-grade carotid lesions). DISCUSSION/CONCLUSIONS: OA flow
      direction is easily studied with CDUS. Reversed OA flow direction is highly
      specific (100%) for severe ipsilateral ICA stenosis or occlusion, with excellent
      positive predictive value, moderate negative predictive value, and limited
      sensitivity. OA flow reversal is not only quite specific for severe ICA disease,
      which may be helpful if the carotid CDUS is difficult or inadequate, but may also
      provide additional hemodynamic insights (i.e., the inadequacy of other collateral
      channels such as the anterior communicating artery). OA evaluation can provide
      important hemodynamic information and should be included as part of carotid CDUS
      if there is any evidence of ICA stenosis or occlusion.

PMID- 11826598
TI  - Neuroimaging characteristics of pseudosubcortical laminar heterotopia.
AB  - Subcortical laminar heterotopia (SLH) is a subtype of malformation of cortical
      development characterized by laminar gray matter between the cortex and
      ventricles, which can vary in thickness and may be continuous or discontinuous.
      The objective of this study is to describe a normal finding of high-resolution
      magnetic resonance imaging that may simulate an SLH. SLH is isointense to cortex
      on both T1- and T2-weighted/FLAIR images, usually both anteriorly and posteriorly
      in location. Conversely, pseudo-SLH is a normal variant present only at the
      posterior aspect of the brain, and with dark signal on both T1- and T2
      weighted/FLAIR images.

PMID- 11826599
TI  - Angioplasty and stenting for symptomatic basilar artery stenosis.
AB  - A 71-year-old man with symptomatic basilar artery stenosis refractory to
      antiplatelet therapy and anticoagulation underwent angioplasty and stenting of
      the basilar artery. The patient was discharged symptom-free on clodiprogel 75 mg
      qd and aspirin 325 mg qd. One month later, he presented with a right frontal
      intracerebral hemorrhage. Angioplasty with stenting for symptomatic basilar
      artery stenosis is feasible. Its role in the therapy of symptomatic basilar
      artery stenosis is not yet defined. Furthermore, the best medical treatment
      postprocedure is yet to be established.

PMID- 11826600
TI  - Hemodynamic effects of innominate artery occlusive disease on anterior cerebral
      artery.
AB  - Stenoses of the innominate artery (IA) may affect flow conditions in the carotid
      arteries. However, alternating flow in ipsilateral anterior cerebral artery (ACA)
      due to IA stenosis is extremely rare. A 49-year-old woman who was evaluated for
      symptomatic cerebrovascular disease presented with right latent subclavian and
      right carotid system steal. Transcranial Doppler examination displayed systolic
      deceleration wave-forms in the right terminal internal carotid artery and
      alternating flow in the right ACA. Magnetic resonance angiography demonstrated
      tight stenosis of the right IA. For a thorough study of the hemodynamic effects
      of IA stenosis, a combination of duplex and transcranial Doppler examination is
      required.

PMID- 11826601
TI  - Isolated pontine progressive multifocal leukoencephalopathy: unusual magnetic
      resonance imaging features.
AB  - Progressive multifocal leukoencephalopathy (PML) is an uncommon opportunistic
      infection that causes focal or multifocal demyelination predominantly in the
      subcortical white matter. The authors describe the clinical and radiographic
      features in 2 unusual cases of PML that were initially isolated to the pons. One
      patient presented clinically with only an isolated sixth cranial nerve palsy.

PMID- 11826602
TI  - Acute disseminated encephalomyelitis confined to brainstem.
AB  - A 21-year-old man was troubled with a subacute history of brainstem involvement
      and a leukocyte pleocytosis in the cerebrospinal fluid. Magnetic resonance
      imaging (MRI) demonstrated a massive lesion with Gd enhancement in the pons.
      Steroid therapy, not antiviral drugs, was dramatically effective for the mass
      reduction and symptom improvement. Over 4 years no recurrence has been
      recognized, so this case was diagnosed to be an unusual case of acute
      disseminated encephalomyelitis (ADEM). ADEM must be included in the differential
      diagnosis for a brainstem mass in MRI.

PMID- 11826603
TI  - Paradoxical brain embolism from thrombus associated with vena caval filter in a
      patient with cancer.
AB  - A 71-year-old man experienced sudden onset of hemiparesis and aphasia. He had a 4
      month history of gallbladder cholangiocarcinoma, complicated with a postoperative
      deep-vein thrombosis (DVT) that necessitated a vena caval filter placement.
      Diffusion-weighted magnetic resonance imaging of the brain showed multiple
      hyperintense foci. Magnetic resonance spectroscopy was compatible with cerebral
      infarction. Abdominal computed tomography showed a thrombus in the inferior vena
      cava extending through the filters. A transcranial Doppler bubble study revealed
      the presence of a right-to-left shunt. Paradoxical cerebral embolism must be
      considered in patients with DVT who have new onset neurologic deficits even in
      the presence of a caval filter.

PMID- 11826604
TI  - Neuroimaging of acute cerebellitis.
AB  - Acute cerebellitis is one of the main causes of acute cerebellar dysfunction in
      childhood and may be infectious, postinfectious, or postvaccination. The etiology
      of acute cerebellitis is usually viral. Varicella zoster, Epsten-Barr, rubeola,
      pertussis, diphtheria, and coxsackie viruses are the most frequently involved
      agents. Diagnosing of acute cerebellitis can sometimes be difficult because the
      patient may present only mild cerebellar signs and the examination of
      cerebrospinal fluid may be normal. The authors present the clinical and
      neuroimaging findings of 2 patients presenting with acute cerebellitis. Their
      magnetic resonance imaging showed hyperintense signal of cerebellar gray matter
      in T2-weighted sequences, which is a strong indication of a diagnosis of acute
      cerebellitis.

PMID- 11826605
TI  - Ictal and interictal single photon emission computed tomography in a patient with
      benign familial infantile convulsions.
AB  - Ictal and interictal single photon emission computed tomography (SPECT) and ictal
      electroencephalography (EEG) were studied in a 3-month-old girl with benign
      familial infantile convulsions (BFIC) to reveal the epileptic focus. There was
      bilateral diffuse propagation from a left frontal lobe focus on the ictal EEG.
      Perfusion in the left frontal region was increased on ictal SPECT and decreased
      on interictal SPECT. Epileptic foci of BFIC showed the same characteristics as
      foci of symptomatic partial epilepsy.

PMID- 11826606
TI  - Misinterpretation of parahippocampal herniation for a posterior fossa tumor:
      imaging and intraoperative findings.
AB  - Tumors of the hippocampal and parahippocampal gyrus are not uncommon, nor are
      lesions of the cerebellopontine and ambient cisterns. Lesions in these areas
      include astrocytomas, meningiomas, gangliogliomas, hamartomas, neurilemomas,
      epidermoids, and dermoids. Preoperative imaging is an important tool that can
      help distinguish lesions, making surgical therapy more targeted and appropriate.
      The authors report a case of a 41-year-old man with right-sided atypical
      trigeminal neuralgia and a left ambient cistern abnormality that was
      radiologically interpreted as a mesial temporal lobe or extramedullary ambient
      cistern mass lesion. Surgical exploration for biopsy revealed an abnormal
      posterior fossa anatomy and a parahippocampal herniation into the
      perimesencephalic cistern. Biopsy confirmed the finding of normal brain.

PMID- 11826607
TI  - Pitfall of electron beam computed tomography angiography in diagnosis of
      subclavian steal syndrome.
AB  - A patient presented with vertebrobasilar insufficiency during exertion. Vertebral
      duplex and transcranial Doppler ultrasonography showed reversal of flow in both
      intracranial and extracranial vertebral and basilar arteries, suggesting
      bilateral subclavian and vertebrobasilar steal. Electron beam computed tomography
      angiography (CTA) showed no evidence of subclavian artery stenosis including
      normal vertebral artery origin on both sides. However, digital subtraction
      angiography revealed complete occlusion of both subclavian arteries with
      retrograde flow from both vertebral and basilar arteries to reconstitute both
      subclavian arteries. This false-negative finding on CTA in detection of
      subclavian steal syndrome (SSS) is due to inappropriate contrast administration
      technique and postprocessing method, inability to differentiate flow direction,
      and lack of hemodynamic time sequences. This study demonstrates a pitfall of CTA
      in diagnosis of SSS compared to more reliable hemodynamic information obtained by
      duplex and transcranial Doppler ultrasonography, and digital subtraction
      angiography.

PMID- 11826608
TI  - Hyperintense basal ganglia on T1-weighted magnetic resonance images in a patient
      with common variable immunodeficiency associated with elevated serum manganese.
AB  - The authors report on a 32-year-old man with common variable immunodeficiency and
      high signal intensity in basal ganglia on T1-weighted images. No signal
      alteration on T2-weighted and postcontrast images was observed. The patient had
      elevated levels of manganese in the serum. The authors conclude that the unusual
      hyperintensity in the basal ganglia area on T1-weighted images resulted from
      manganese deposition due to liver dysfunction.

PMID- 11826609
TI  - Flumazenil responsive ornithine transcarbamylase deficiency encephalopathy:
      clinical and radiographic features.
AB  - A 22-year-old woman with a negative urine drug screen and somnolence rapidly
      reversed by intravenous flumazenil was found to have elevated ammonia levels and
      punctate calcifications of the subcortical frontal white matter. Abnormally high
      levels of orotic acid were found in serum and urine, confirming the diagnosis of
      ornithine transcarbamylase deficiency. Although computed tomography findings are
      non-specific, young patients with unexplained hyperammonemic states of somnolence
      reversed by flumazenil should be screened for this X-linked recessive metabolic
      disorder.

PMID- 11826610
TI  - Isolated septum pellucidum agenesis in an adult.
AB  - Septum pellucidum agenesis is frequently associated with other cerebral
      malformations. Its isolated agenesis is quite rare. In the literature, all
      reported cases were diagnosed in early childhood. The authors present an unusual
      case of isolated septum pellucidum agenesis detected in adulthood with computed
      tomography and magnetic resonance imaging.

PMID- 11826611
TI  - Screening for intracranial stenosis with transcranial Doppler: the accuracy of
      mean flow velocity thresholds.
AB  - BACKGROUND: Patients with 50% intracranial arterial stenosis may require more
      intensive therapies for stroke prevention. Transcranial Doppler (TCD) is a
      convenient noninvasive screen for intracranial stenosis. The accuracy of
      different mean flow velocity (MFV) thresholds for determining the degree of
      stenosis remains uncertain. METHODS: The authors prospectively compared the
      accuracy of TCD criteria and MFV thresholds to magnetic resonance, computed
      tomography, and digital subtraction angiography in patients with symptoms of
      recent or remote stroke or transient ischemic attack. Stenosis on angiography was
      measured as 0%, < 50%, or > or = 50% diameter reduction. RESULTS: Of 136
      consecutive patients, 33 (24%) had distal internal carotid artery (ICA), middle
      cerebral artery (MCA), posterior cerebral artery, or basilar artery stenosis on
      angiography (14 patients [10%] were excluded due to incomplete TCD examinations,
      mainly from a lack of temporal windows). TCD showed 31 true-positive, 9 false
      positive, 2 false-negative, and 94 true-negative studies. For all vessels, TCD
      had a sensitivity of 93.9% (confidence interval [CI] = 89%-98%), a specificity of
      91.2% (CI = 87%-96%), a positive predictive value (PPV) of 77.5%, and a negative
      predictive value (NPV) of 97.9%. The trade-off in sensitivity and specificity for
      MCA MFV thresholds was as follows: MFV > or = 80 cm/s had a sensitivity of 100%,
      a specificity of 96.9% (CI = 94%-99%), a PPV of 84%, and an NPV of 100%. MFV > or
      = 100 cm/s had a sensitivity of 100%, a specificity of 97.9% (CI = 96%-99%), a
      PPV of 88.8%, and an NPV of 94.9%. MFV > or = 120 cm/s had a sensitivity of 68.7%
      (CI = 61%-78%), a specificity of 100%, a PPV of 100%, and an NPV of 94.9%.
      Reasons for false-positive findings include collateralization of flow in the
      presence of proximal ICA stenosis and prestenotic to stenotic MCA velocity ratios
      of 1: < or = 2. CONCLUSION: TCD is both sensitive and specific in identifying >
      or = 50% intracranial arterial stenosis. A MFV threshold cutoff of 100 cm/s has
      an optimal sensitivity and specificity trade-off for > or = 50% MCA stenosis. To
      help avoid false-positive results, a prestenotic to stenotic MCA velocity ratio
      of 1: > or = 2 should be used in addition to the MFV threshold.

PMID- 11826612
TI  - Elevated basal ganglia glucose metabolism in cyclosporine neurotoxicity: a
      positron emission tomography imaging study.
AB  - Abnormally increased 18F-fluorodeoxyglucose uptake in the basal ganglia was noted
      by positron emission tomography (PET) in a 37-year-old bone marrow transplant
      patient who had severe intention tremors of his hands and a progressive
      psychiatric change with social withdrawal and flat affect. This is the first PET
      report on metabolic abnormalities in cyclosporine neurotoxicity. It emphasizes
      the need for more research to understand the pathophysiology of these changes.

PMID- 11826613
TI  - Ligand-dependent and -independent processes in B-cell-receptor-mediated
      signaling.
AB  - The B cell antigen receptor (BCR) is a protein complex expressed on the surface
      of immature and mature B cells. After ligand-induced aggregation, this complex
      generates signals that lead to a variety of biological outcomes, including
      survival, proliferation and differentiation. During B cell development
      intermediate forms of the BCR are expressed on the surface. The composition of
      these pro- and preBCR complexes reflects the ordered assembly of the BCR complex
      and they exist to generate signals for positive selection at defined
      developmental checkpoints. Because these receptors lack the ability to bind
      conventional ligands, the pro- and preBCR have been postulated to signal via
      ligand-independent processes. This ligand-independent or constitutive signal may
      also play a role in the survival of peripheral mature B cells. Here we discuss
      the evidence for ligand-independent functions for the BCR and postulate how it
      may be regulated and linked to biological processes associated with B cell
      development and survival.

PMID- 11826614
TI  - Maintenance and loss of self-tolerance in B cells.

PMID- 11826615
TI  - Somatic hypermutation in human B cell subsets.

PMID- 11826616
TI  - Antibody repertoires in infants and adults: effects of T-independent and T
      dependent immunizations.
AB  - Polysaccharide(PS)-encapsulated bacteria such as Streptococcus pneumoniae,
      Haemophilus influenzae, and Neisseria meningitidis are among the most prevalent
      bacterial pathogens of humans. Infections caused by these organisms are both
      common (otitis media, sinusitis) and severe (meningitis, bacteremia). Antibodies
      directed against the capsular PS of encapsulated bacteria prevent infection by
      promoting opsonophagocytic killing. Most bacterial PS, however, are type II T
      cell-independent (TI-2) antigens that are poorly immunogenic in young children at
      highest risk of developing disease. Conjugation of bacterial PS to a protein
      carrier converts the immune response to a T-cell-dependent (TD) form and
      significantly improves the immunogenicity of PS, especially in infants. H.
      influenzae type b (Hib) is a major cause of invasive infection in non-immune
      children. The medical importance of this pathogen and the availability of both TI
      2 and TD Hib PS vaccine formulations have made the human anti-Hib-PS immune
      response an excellent model for the study of the biology of these B cell
      responses.

PMID- 11826617
TI  - Naive and memory B cells in T-cell-dependent and T-independent responses.
AB  - This review focuses on the properties and roles of distinct subsets among the
      primary and the memory B lymphocytes regarding their contribution to helper-T
      cell-dependent and -independent antibody responses. The naive/memory B cell
      functions are explained in the context of current concepts on the basic
      mechanisms of humoral immunity. Differences between murine and human B cells are
      also discussed.

PMID- 11826618
TI  - Functions of antibodies in the regulation of B cell responses in vivo.

PMID- 11826619
TI  - Isotype-dependent pathogenicity of autoantibodies: analysis in experimental
      autoimmune hemolytic anemia.

PMID- 11826620
TI  - Immunomodulation of autoimmune diseases by high-dose intravenous immunoglobulins.

PMID- 11826622
TI  - Lead poison prevention: a comparative review of brochures.
AB  - Although eliminating lead from the environment is the most effective way to
      prevent lead poisoning, outreach and education also must be addressed. This study
      reports a consensus summary of lead-poisoning prevention topics and reading
      levels derived from state brochures. This information may be useful in the
      evaluation and design of future lead prevention brochures. A point system was
      used to assess the readability and topic content of 20 brochures from 11 states.
      Only half of the brochures were written at the targeted grade level. Frequently
      covered topics were wash hands and face, provide foods that contain good sources
      of key nutrients, and use damp cleaning methods when dusting and mopping. The
      findings about topics and reading levels can be used throughout the development
      of lead-hazard prevention brochures.

PMID- 11826621
TI  - Transboundary movement of hazardous wastes into Lebanon: Part 2. Environmental
      impacts and the need for remedial actions.
AB  - This paper discusses the transboundary movement of hazardous wastes (the "silent
      trade") into Lebanon in terms of environmental impacts and remedial actions. It
      highlights the projected impacts on potable-water quality, the exposure of the
      groundwater aquifer, and the status of quality control programs. The public
      responses to these problems are presented and characterized in terms of mistrust
      and rejection. The constraints developing countries face in handling
      environmental impacts and undertaking remedial actions are emphasized. The vision
      derived from the decade covered (1990-2000) emphasizes the need for international
      collaboration, through Basel Convention efforts, to control the transboundary
      movement of hazardous wastes and the disposal of such wastes. The need for
      "global harmonization" should be given serious consideration.

PMID- 11826623
TI  - HACCP lessons.

PMID- 11826624
TI  - Local government environmental advisory boards.

PMID- 11826625
TI  - Back-door visits and open-field inspections: some comments on the legality of
      inspections without owner permission.

PMID- 11826626
TI  - The significance of geography in environmental health, or what can geography do
      for the environmental health profession?

PMID- 11826627
TI  - Indoor mold contamination--a threat to health?

PMID- 11826628
TI  - A superbly accurate motorized psychrometer.

PMID- 11826629
TI  - Transboundary movement of hazardous wastes into Lebanon: Part 1. The silent
      trade.
AB  - This paper discusses the transboundary movement of hazardous wastes into
      developing countries, frequently referred to as the "silent trade," and the new
      efforts by the Basel Convention to control the international movement of
      hazardous wastes. The importation of hazardous wastes into Lebanon is examined in
      terms of waste trade activities (e.g., types, quantities, and management
      responses) as of 1987. The focus is on the national response, the roles played by
      different parties (e.g., politicians, expert groups, nongovernmental
      organizations, international organizations, and mass media) and their impact on
      the current status of events. Key challenges facing developing countries in
      managing silent-trade activity are identified in terms of environmental health
      and safety implications.

PMID- 11826630
TI  - Update in pediatric resuscitation.
AB  - This article updates research concerning the resuscitation of a pediatric
      patient. The topics discussed include the state of pediatric life support, the
      current guidelines, the management of those guidelines, and coping with death.

PMID- 11826631
TI  - Common abdominal emergencies in children.
AB  - Because young children often present to EDs with abdominal complaints, emergency
      physicians must have a high index of suspicion for the common abdominal
      emergencies that have serious sequelae. At the same time, they must realize that
      less serious causes of abdominal symptoms (e.g., constipation or gastroenteritis)
      are also seen. A gentle yet thorough and complete history and physical
      examination are the most important diagnostic tools for the emergency physician.
      Repeated examinations and observation are useful tools. Physicians should listen
      carefully to parents and their children, respect their concerns, and honor their
      complaints. Ancillary tests are inconsistent in their value in assessing these
      complaints. Abdominal radiographs can be normal in children with intussusception
      and even malrotation and early volvulus. Unlike the classic symptoms seen in
      adults, young children can display only lethargy or poor feeding in cases of
      appendicitis or can appear happy and playful between paroxysmal bouts of
      intussusception. The emergency physician therefore, must maintain a high index of
      suspicion for serious pathology in pediatric patients with abdominal complaints.
      Eventually, all significant abdominal emergencies reveal their true nature, and
      if one can be patient with the child and repeat the examinations when the child
      is quiet, one will be rewarded with the correct diagnosis.

PMID- 11826632
TI  - Common emergent pediatric neurologic problems.
AB  - Although there are a variety of neurologic disease processes that the emergency
      physician should be aware of the most common of these include seizures, closed
      head injury, headache, and syncope. When one is evaluating a patient who has had
      a seizure, differentiating between febrile seizures, afebrile seizures, and SE
      helps to determine the extent of the work-up. Febrile seizures are typically
      benign, although a diagnosis of meningitis must not be missed. Educating parents
      regarding the likelihood of future seizures, and precautions to be taken should a
      subsequent seizure be witnessed, is important. The etiology of a first-time
      afebrile seizure varies with the patient's age at presentation, and this age
      specific differential drives the diagnostic work-up. A follow-up EEG is often
      indicated, and imaging studies can appropriate on a nonurgent basis. Appropriate
      management of SE requires a paradigm of escalating pharmacologic therapy, and
      early consideration of transport for pediatric intensive care services if the
      seizure cannot be controlled with conventional three-tiered therapy. Closed head
      injury frequently is seen in the pediatric emergency care setting. The absence of
      specific clinical criteria to guide the need for imaging makes management of
      these children more difficult. A thorough history and physical examination is
      important to uncover risk factors that prompt emergent imaging. Headaches are
      best approached by assessing the temporal course, associated symptoms, and the
      presence of persistent neurologic signs. Most patients ultimately are diagnosed
      with either a tension or migraine headache; however, in those patients with a
      chronic progressive headache course, an intracranial process must be addressed
      and pursued with appropriate imaging. Syncope has multiple causes but can
      generally be categorized as autonomic, cardiac, or noncardiac. Although vasovagal
      syncope is the most common cause of syncope, vigilance is required to identify
      those patients with a potentially fatal arrhythmia or with heart disease that
      predisposes to hypoperfusion. As such, all patients who present with syncope
      should have an ECG. Additional work-up studies are guided by the results of
      individual history and physical examination.

PMID- 11826633
TI  - Hematologic emergencies in the pediatric emergency room.
AB  - The complete blood count (CBC) describes the three hematopoietic lineages (i.e.,
      the erythrocytes, leukocytes, and platelets), and it is an essential diagnostic
      component in numerous clinical situations. The pediatric CBC and hematologic
      problems in children may significantly differ from that of adults. In this
      article, special features of pediatric hematologic emergencies are highlighted.

PMID- 11826634
TI  - Contemporary trends in pediatric sedation and analgesia.
AB  - The ability to provide safe, effective procedural sedation and analgesia is a
      necessary skill for physicians caring for the acutely ill or injured pediatric
      patient. They physician should be familiar with the agent(s) chosen, including
      dosage, duration, adverse effects, and contraindications. The choice of agent and
      regimen should be individualized for the patient and situation. Successful
      outcomes depend on performing careful pre- and post-sedation evaluations,
      following appropriate monitoring and equipment guidelines, and having the
      knowledge and skills to manage any adverse cardiorespiratory event.

PMID- 11826635
TI  - Pediatric toxicologic concerns.
AB  - Pediatric poisonings account for significant morbidity in the United States each
      year. Clinicians must keep current with advances in toxicology to be familiar
      with the latest recommended treatment regimens and antidotes. They also must be
      familiar in identifying toxidromes and important physical examination findings.
      Having these skills can enable the clinician to determine who is at risk for
      significant morbidity or mortality and to provide the appropriate medical care.

PMID- 11826636
TI  - Common complaints in the first 30 days of life.
AB  - Visits to the emergency department (ED) by neonates and their parents can cause
      anxiety for parents and the ED staff. Many of the presenting complaints are
      unique to the neonatal population, and an understanding of both common problems
      and true medical emergencies is paramount. This article discusses the complaints
      the EDs have seen more frequently as a result of earlier newborn discharges from
      hospitals.

PMID- 11826637
TI  - Management of fever in infants and children.
AB  - There is no question that fever is a source of great consternation for parent and
      physician alike; however, it is impossible to predict with certainty the outcome
      of every febrile illness. Inherent in the words diagnostic impression is a degree
      of uncertainty. The only question remaining is how much uncertainty is in the
      best interest of the child. Physicians try to use the existing scientific data to
      best determine the prevalence of disease and outcome. At the same time, they must
      recognize the limitations of both the data and their ability to be generalized to
      every population. Everything clinicians do has risks and costs, which they must
      balance against the incidence of complications and the benefits of testing. To
      take away clinical judgment makes physicians technicians not clinicians.

PMID- 11826638
TI  - Appropriate use of antibiotics for common infections in an era of increasing
      resistance.
AB  - In many respects, antibiotics have changed medicine forever. Countless lives have
      been enhanced and saved with antibiotic use. Unfortunately, the medical community
      has opened Pandora's box through the casual distribution of outpatient
      antibiotics. Society will indeed suffer, as well as the medical profession, if
      antibiotics are not used judiciously. To date, the rate of penicillin resistance
      has steadily risen in North America and in many other areas of the world. Much of
      the increase in resistance has been caused by the distribution of antibiotics for
      viral infections (e.g., bronchitis, colds, or purulent nasal discharge) as well
      as nonstreptococcal throat infections. Parental pressure for physicians to
      prescribe antibiotics also has contributed to the rise in antibiotic resistance.
      The authors have discussed many common pediatric ED infections and have
      illustrated the key points for making the diagnosis of each. In addition, the
      authors also recommend the appropriate choice of antibiotics for each disease
      process, with an emphasis on narrow-spectrum, first-line antimicrobials.
      Physicians, as the "holders of the prescription pad," should be aware of the
      problems with increasing bacterial resistance especially ED practitioners who
      work on the front line. In addition, families and patients should be educated
      about the harm of inappropriate antibiotic use. The AAP publishes pamphlets for
      parents that discuss these issues. It is believed, as was seen in Finland and
      Japan, that judicious use of antibiotics leads to a decrease in resistant
      bacteria and prolong antibiotic usefulness. This is an issue of great importance
      to the long-term health of patients. What Benjamin Rush stated in 1789 is true
      today: "Do not condemn, or oppose, unnecessarily, the simple, prescriptions of
      your patients. Yield to them in matters of little consequence but maintain an
      inflexible authority over matters that are essential to life."

PMID- 11826639
TI  - New approaches to respiratory infections in children. Bronchiolitis and croup.
AB  - Croup is a disease that is commonly seen in children younger than the age of 6
      years. The cause is viral, with parainfluenza viruses and RSV being the two most
      common pathogens. Treatment consists primarily of supportive care, and parents
      usually have tried humidification and cool air exposure before the child presents
      to the ED. Children with moderate to severe croup are usually seen in the ED. The
      use of steroids in an oral preparation results in a clinical improvement of
      outpatients with mild to moderate croup and reduces the need for hospitalization.
      The dosage range for oral dexamethasone is 0.15 mg/kg to 0.6 mg/kg. Nebulized
      budesonide may also be used. Racemic or L-epinephrine, both of which are equally
      effective, can be used for symptomatic treatment in severe croup. After
      administration of racemic or L-epinephrine, hospitalization is not automatic and
      patients can be discharged safely from the ED after a 3-hour of observation
      period. There should be no respiratory distress, and the patient should have
      access to follow-up and emergency care if needed.

PMID- 11826640
TI  - [The application of sodium hyaluronate in joint diseases].
AB  - OBJECTIVE: To review the physiological function of sodium hyaluronate in joints
      and its clinical applications. METHODS: Many literatures were reviewed and
      analysed on therapeutic mechanism and the application foreground of sodium
      hyaluronate. RESULTS: Extrinsic sodium hyaluronate plays an important role in
      improving synovial fluid and protecting cartilages as well as suppressing
      inflammation, so it is used in the treatment of joint diseases such as knee
      osteoarthritis, rheumatoid arthritis or temporomandibular osteoarthritis.
      CONCLUSION: Sodium hyaluronate possesses a good applied prospect in joint
      diseases.

PMID- 11826642
TI  - [Efficacy of intra-articular injection of sodium hyaluronate in post-operation
      treatment of the knee].
AB  - OBJECTIVE: To investigate the effects of intra-articular injection of sodium
      hyaluronate in post-operation treatment of the knee. METHODS: From January 1998
      to February 2001, 4 ml of sodium hyaluronate injection was injected into the knee
      joint of the 134 cases at the end of arthroscope operation, or the 91 cases
      undergoing open operation of the knee at the time when the drain tube was removed
      (treatment group). Five days after operation, the hydrarthrosis was removed and 2
      ml of sodium hyaluronate was injected into the knee joint. According to the
      patient's condition, injection of sodium hyaluronate was performed once a week
      for several weeks. Clinical evaluation was made by evaluating pain visual analog
      scale (VAS) and painless range of movement (ROM) of the joint at every definite
      point of time. The 85 patients in control group used nothing at the same time.
      RESULTS: The VAS score of patients in the treatment group was significant lower
      than that of the control group. The period to the maximal painless ROM of the
      joint was 6 days in the treatment group after open operation, while 9 days in the
      control group. CONCLUSION: Sodium hyaluronate appears effective in relieving post
      operation pain of the knee joint.

PMID- 11826641
TI  - [Randomized controlled trial of sodium hyaluronate for degenerative disorders of
      the temporomandibular joint].
AB  - OBJECTIVE: To assess the effect of sodium hyaluronate (HA) for degenerative
      disorders of the temporomandibular joint (TMJ). METHODS: A prospective randomized
      controlled clinical trial was conducted. The experimental group received
      injections in the upper compartments of the involved TMJs with 1% HA 6 mg,
      whereas the control group received prednisolone (PS) 12.5 mg once a week. Three
      to four injections were as one course. Before and one week after the treatment
      courses, clinical symptoms, amount of interleukin-6 (IL-6) and total protein of
      synovial fluid were measured and compared. RESULTS: Sixty-seven patients were
      included and 4 out of them were dropped out. There were 12 males and 51 females,
      among them, 14 cases with synovitis, 21 with anterior disc displacement without
      reduction and 28 with osteoarthritis of the TMJ. Thirty-five patients allocated
      in HA group and 28 in PS group. Both drugs could relieve the clinical symptoms of
      TMJ degenerative disorders. In HA group, marked improvement rate was 51.43% and
      failure rate was 2.86%, whereas marked improvement rate 39.29% and failure rate
      17.86% in PS group. The declined levels of IL-6 in synovial fluid was notably
      greater in HA group than those in PS group. CONCLUSION: Intra-articular injection
      of HA is effective and safe to treat TMJ degenerative disorders with mild adverse
      reactions, better in terms of effective rate and declined level of IL-6 than PS.

PMID- 11826643
TI  - [Clinical study on sodium hyaluronate intra-articular injection in treatment of
      degenerative osteoarthritis of knee].
AB  - OBJECTIVE: To evaluate the clinical effect of sodium hyaluronate (SH) intra
      articular injection in treatment of degenerative osteoarthritis (DOA) of knees.
      METHODS: One hundred patients (116 knees) suffered from DOA were treated by SH
      injection intra-articularly once a week for three times. According to Lysholm
      scoring, clinical signs such as pain, swelling, excludes, range of movement
      (ROM), and the ability of walking, going upstairs and downstairs, squatting,
      running, were assessed before and after treatment. RESULTS: Ninety-six cases were
      followed up for 1 to 6 months. There were obvious improvements in the signs and
      function of knee in 39 patients (40.6%), only some improvements in 48 patients
      (50.0%), and no obvious improvements in other 9 patients (9.4%). The total
      effectiveness rate was 74.0%. No toxic or side effect was observed. CONCLUSION:
      Intraarticular injection of SH has a positive effect in relief of clinical
      symptoms and in improvement of articular function of DOA of knee.

PMID- 11826644
TI  - [Clinical study of sodium hyaluronate in supplementary treatment of comminuted
      fracture of ankle].
AB  - OBJECTIVE: To investigate the effects of sodium hyaluronate in supplementary
      treatment of comminuted fracture of ankle. METHODS: Thirty-seven patients
      suffered from comminuted fracture of ankle were operated for restoration by
      routing methods, and received 2 ml of sodium hyaluronate injection intra
      articularly before the closure of incision. The ankle was fixed and given the
      second intra-articular injection on the 3rd day after operation. Then, the
      patients were given sodium hyaluronate injection intra-articularly at a week
      intervals till the paste was removed after 4 weeks. All patients were followed
      up. The clinical results were evaluated by measuring the symptoms of pain, and
      the function of walking and other daily living activities. RESULTS: All the
      patients were followed up for 6 to 27 months, among them, 30 patients were cured
      completely without any symptoms, the ankle function for walking and daily living
      activities was normal, 6 patients felt pain with violent activity or walking
      exceeding 1 km, one patient suffered from comminuted fracture with compressed
      depression was not improved due to his ankle being not restored properly.
      CONCLUSION: Intra-articular injection of sodium hyaluronate is an effective
      supplementary treatment for comminuted fracture of ankle.

PMID- 11826645
TI  - [The clinical effects of percutaneous lumbar discectomy combined with sodium
      hyaluronate in the treatment of lumbar intervertebral disc herniation].
AB  - OBJECTIVE: To investigate the therapeutic effect of percutaneous lumbar
      discectomy (PLD) combined with sodium hyaluronate (SH) injection in the treatment
      of lumbar intervertebral disc herniation. METHODS: Forty-eight patients suffered
      from lumbar disc herniation were divided into two groups and treated by PLD
      combined with SH injection into epidural cavity (treatment group) or single PLD
      (control group) respectively. All patients were followed up for 24 months. The
      therapeutic effects in both groups were assessed and compared according to
      Macnab's criterion. RESULTS: The patients in the treatment group got much more
      significant improvement than those in the control group, with shorter therapeutic
      course and more safety. CONCLUSION: PLD combined with SH injection into epidural
      cavity is more effective and safety in the treatment of lumbar disc herniation
      than of pure PLD.

PMID- 11826646
TI  - [Prevention effects of sodium hyaluronate on nerve root adhesion after lumbar
      intervertebral disc protrusion].
AB  - OBJECTIVE: To observe the effects of sodium hyaluronate on nerve root adhesion
      after operation of lumbar disc protrusion (LDP). METHODS: From April 1996 to June
      2001, 152 cases with LDP were performed the removal of nucleus pulposus under
      endoscope. After operation, 2 ml of sodium hyaluronate were injected. The
      clinical results were evaluated by clinical symptom, straight leg raising test,
      patient's satisfaction degree and back pain. RESULTS: All the patients were
      followed for 1 month to 3 years. The average angle of straight leg raising test
      increased from 26 degree preoperatively to 62 degree postoperatively. The
      patient's pain were markedly relieved. Patient's satisfactory degree were 86.8%.
      CONCLUSION: The injection of sodium hyaluronate after operation of LDP has effect
      on preventing postoperative nerve root adhesion.

PMID- 11826647
TI  - [The clinical study of adhesion prevention of sodium hyaluronate in flexor tendon
      surgery].
AB  - OBJECTIVE: To evaluate the effects of sodium hyaluronate on adhesion prevention
      after flexor tendon surgery. METHODS: In 47 cases with the flexor tendon surgery,
      two kinds of sodium hyaluronate jelly preparations were injected into the tendon
      sheath before suture. Preparation I (20 mg/2 ml) was for group A (17 patients)
      and preparation II (20 mg/2 ml) was for group B (16 patients). The control group
      (group C, 14 patients) were treated in the same way except injection of sodium
      hyaluronate. The functions of afflicted fingers including flexibility, pain and
      swelling were measured immediately, at the first, second and the third month
      after operation. RESULTS: All 47 patients were followed up 1 to 3 months. 64.71%
      patients in group A and 68.75% in group B showed significant improvement. There
      were significant difference compared with group C (P < 0.05). There were no
      significant adverse reactions were observed in all groups. CONCLUSION: Two sodium
      hyaluronate preparations have effects in adhesion prevention after flexor tendon
      surgery with safety and expedience.

PMID- 11826648
TI  - [Epidermal growth factor stimulates tissue repair in skin through skin stem cell
      activation].
AB  - OBJECTIVE: To explore the possible mechanisms of skin regeneration through the
      epidermal stem cells stimulated by epidermal growth factor (EGF). METHODS: At 8
      and 14 days after treatment with EGF, the tissue specimens from 8 skin ulcered
      patients who were treated with EGF were used to evaluate the distribution and
      differentiation of epidermal stem cells. The expression of beta 1 integrin,
      keratin 19 (K19), keratin 14(K14) and keratin 10 (K10) in skin was detected with
      SP immunohistochemical methods. Hematoxylin and eosin staining method were used
      to observe the tissue structure. Another 7 biopsies from ulcered patients without
      EGF management were used as the control. RESULTS: The results from the
      hematoxylin and eosin staining showed that the epidermis in EGF treated wounds
      was thick and the epidermal ridges were enlarged both in 8 and 14 days compared
      with those in control skin. Immunohistochemical staining from beta 1 integrin and
      K 19 showed that all tissues treated with EGF were rich in epidermal stem cells
      both in 8 and 14 days. These stem cells were bigger in size and larger in number
      and localized at the base of the epidermis. In contrast, the positive expression
      cells of beta 1 integrin and K 19 in control group in the same time were scanty.
      It was found that there were some stem cell islands in epidermis treated with EGF
      in day 14 and absent from the control group. The expression of K14 and K10 could
      be observed in those terminally differentiating epidermal cells in both groups.
      CONCLUSION: The results indicate that the possible mechanisms of skin
      regeneration stimulated by EGF comes from the mitogenic effects and
      differentiation of skin stem cells.

PMID- 11826649
TI  - [The expression of laminin in the intermingled skin transplantation of allograft
      and autograft].
AB  - OBJECTIVE: To explore the healing mechanism of full-thickness wound treating by
      the intermingled skin transplantation of large sheet allograft with autograft
      through studying the expression of laminin (LN). METHODS: Thirty-six SD rats with
      10% to 15% of total body surface area (TBSA) full-thickness were made. After 3
      days, the devitalized tissue were excised and transplanted a large sheet of
      allograft from Wistar rats and islets of autografts were implanted 3 days later.
      On day 3, 5, 7, 14, 21 after allografting, the expression of LN in the grafts
      were detected by immunohistochemistry. RESULTS: On the 7th day postallografting,
      LN, which played positive action of epidermal cell adhesion, still retained in
      the allodermis after the rejection of alloepidermis occurred. On the 14th day
      postallografting, there appeared scattered LN underneath the epidermal cells
      migrating from islets of autografts. On the 21st day postallografting, LN in the
      basement membrane of skin grafts had completely formed. CONCLUSION: The
      intermingled transplantation of large sheet allograft with autograft may provide
      components of basement membrane for wound healing, which may help to improve the
      appearance and function of skin.

PMID- 11826650
TI  - [Effect of the endoexpander pressure of continuous and constant pressure
      expansion on the drug permeability].
AB  - OBJECTIVE: To investigate the effect of the endoexpander pressure of continuous
      and constant pressure expansion on the drug permeability. METHODS: The expanders
      were divided into two groups, the normal expansion and the continuous and
      constant pressure expansion (4.6 kPa). Each expander was filled with 0.2%
      Metronidazole, then the expanders were immersed wholly in normal saline and
      sealed totally. At several intervals over 72 hours, the surrounding saline was
      sampled and the drug concentration of the sample was measured respectively.
      RESULTS: Both groups were permeable to the Metronidazole and the concentration
      outside the expander would reach the effective concentration in 48 hours. The
      drug concentration of the continuous and constant pressure expansion was higher
      than that of the normal one and there was significant difference between the two
      groups (P < 0.01). CONCLUSION: The endoexpander pressure in continuous and
      constant pressure expansion can enhance the drug permeability. In view of this,
      in the course of continuous and constant pressure expansion, 0.2% Metronidazole
      can be used to prevent and control the infection.

PMID- 11826651
TI  - [Application of recombinant human epidermal growth factor on chronic ulcer
      wound].
AB  - OBJECTIVE: To observe the effect of recombinant human epidermal growth factor
      (rhEGF) on healing of chronic ulcer wound. METHODS: From January 1999 to January
      2001, twenty-six patients with chronic wounds were adopted in this study. Among
      them, there were 17 males and 9 females, aged from 12 to 61 years. The area of
      the chronic wound varied from 3 cm x 3 cm to 5 cm x 8 cm and the disease course
      was 7 to 16 days. These patients were treated with rhEGF in the way of sprinkling
      locally (400 U/10 cm2). Another 26 patients with chronic wounds were adopted as
      the control group and were treated with 0.9% saline in the same way. The healing
      time of wounds and the local and systemic reactions of patients were observed.
      RESULTS: The healing time of chronic wounds was shorter obviously to about 7 days
      with rhEGF than that of the control group and there was significant difference
      between the two groups(P < 0.01). CONCLUSION: rhEGF can obviously promote the
      healing of chronic ulcer wound.

PMID- 11826652
TI  - [Ultrastructural changes after denervation of different muscles].
AB  - OBJECTIVE: To observe the ultrastructural changes and number of satellite cells
      in different muscles with different denervation interval and investigate the
      mechanism of denervation atrophy. METHODS: Muscles of different denervation
      interval were harvested, which were 6 biceps brachii and 6 abductor digiti
      minimi. The ultrastructure of the samples were observed under transmission
      electron microscope. The number of nucleus and satellite cells were counted to
      calculate the percentage content of satellite cells. RESULTS: In early stage of
      denervation, the myofilament and sarcomere of the majority were well oriented.
      The nucleoli of some muscle cell nucleus were enlarged and pale. Vacuolarization
      was also seen in some mitochondria. There was no obvious proliferation of
      collagen fiber around myofibers. After denervation of half a year, rupture and
      disorientation of myofilament was seen. The nucleus became smaller, dark stained,
      and some of them were condensed. There was proliferation of fibroblasts, adipose
      cells and collagen fibers around myofibers. Motor endplate was not recognized one
      year after denervation. In the early stage of denervation, satellite cell
      percentage of the two muscles was relatively high. It then declined with time.
      One year after denervation, satellite cells were scarcely detected. Comparison of
      the curves for satellite cell declination in two muscles revealed that the
      declination of the abductor digiti minimi was faster than that of biceps brachii.
      Decrease of the former started 3 months after denervation, while the latter
      started after 6 months. CONCLUSION: Disappearing of motor endplate and
      proliferation of collagen fibers are main factors that affect the treatment
      outcome in late cases. Decrease of satellite cell number is another cause. The
      correlation of less satellite cell in abductor digiti minimi and poorer recovery
      of hand intrinsic muscles indicates that increment of satellite cells in long
      term denervated muscles may be one of the effective measures to improve treatment
      outcome.

PMID- 11826653
TI  - [Transposition of pedicled sternocleidomastoid muscle for repair of facial
      paralysis in late stage].
AB  - OBJECTIVE: To explore a new surgical approach to repair facial paralysis in late
      stage, using regional transposition of pedicled sternocleidomastoid muscle for
      the dynamic reanimation of the paralyzed face. METHODS: Seven cases with facial
      paralysis in late stage from December 1999 were treated and followed up for 10
      months before clinical evaluation. In all of the cases, the sternal and
      clavicular branches of the sternocleidomastoid muscle were both elevated from
      their bony attachments, with the mastoid insertion left in situ as the pedicle
      for blood supply and accessory nerve maintained in it. The muscle strips were
      transposed and sutured to the orbicularis oris around the mouth corner on the
      paralyzed side. RESULTS: Static asymmetry of nose and oral commissure on the
      paralyzed side were corrected immediately after operation, and the movement of
      the oral commissure recovered one week after operation. Symmetric smiling was
      observed in one month and all of the oral movements recovered in 10 months
      postoperatively. CONCLUSION: The new approach to repair facial paralysis in late
      stage by regional transposition of pedicled sternocleidomastoid muscle is
      effective in restoration of both static and dynamic symmetry of nose and mouth,
      and in recovery of the facial expression and the oral commissure.

PMID- 11826654
TI  - [Comparative study on effects of sodium hyaluronate and prednisolone injections
      on experimental temporomandibular joint osteoarthritis of rabbits].
AB  - OBJECTIVE: To assess the treatment effect of sodium hyaluronate (HA) on
      experimental temporomandibular joint (TMJ) osteoarthritis of rabbits in
      comparison with prednisolone (PS). METHODS: The upper compartments of both TMJs
      of 12 Japanese White Ear Rabbits were injected with 0.2 ml of 1.6% papain, 3 days
      after the right TMJs were injected again with same amount of papain to induce
      osteoarthritis with different severity levels. Except 1 rabbit was died
      accidentally. After one week from final injection of papain, the upper
      compartments of both TMJs of 6 rabbits were injected with HA 1.3 mg, 5 rabbits
      with PS 1.6 mg weekly for 4 times. At 3, 5 and 7 weeks after the final injection,
      the rabbits were sacrificed and the TMJs were pathologically examined. RESULTS:
      The TMJs receiving PS showed predominant structural disorganization, and the
      right TMJs had much severe pathology. The manifestations were fibrillation,
      thinner or flaking of the articular cartilage of the temporal part of the joint,
      and the articular surface was covered with fibrous tissue. Whereas the TMJs
      receiving HA injections demonstrated limited changes of cartilage, less
      fibrillation, only local loss of cartilage on outside layer of the surface. In
      vicinity of the defect area, cluster of the chondrocytes appeared. Pathological
      scores of the TMJs receiving HA were significantly less than those of the TMJs
      revieving PS. CONCLUSION: The results suggest that hyaluronate have effect of
      cartilaginous reparation and protection for the osteoarthritis of rabbit. While
      prednisolone has no help or worsened for articular cartilage reparation.

PMID- 11826655
TI  - [Treatment of fracture of femoral neck in the aged with artificial hip joint
      replacement].
AB  - OBJECTIVE: To evaluate the clinical effect of total hip joint replacement and
      hemiarthroplasty in treatment of fracture of femoral neck in old patients.
      METHODS: One hundred and ten cases with femoral neck fracture in the aged, 70 to
      106 years old, from Aug 1990 to Aug 1999 were reviewed, 96 cases were followed
      up, among which 52 cases received total hip joints replacement and the other 44
      cases received hemiarthroplasty. All of the 96 cases were followed up for 15 to
      112 months, averaged 51 months, and were evaluated in operation procedures, post
      operative recovery and joint function according to Harris Scoring. RESULTS: The
      operation time of total hip joints replacement was 20 minutes longer, bleeding
      volume was 120 ml larger, and post-operative drainage was 140 ml more, in
      average, than those in hemiarthroplasty. There was no obvious difference between
      the two types of operation in bed-resting time, length of stay and hospitalizing
      costs. According to Harris Scoring, there were 38 cases of excellent in
      hemiarthroplasty (86.4%) and 48 cases of excellent in total hip joints
      replacement (92.3%). CONCLUSION: Both of the artificial joint replacements are
      reasonable choices for treatment of fracture of femoral neck in old patients, but
      total hip joints replacement is recommendable for those comparatively younger
      patients with good systematic status, and hemiarthroplasty is a good option for
      those elderly with some systematic diseases.

PMID- 11826657
TI  - [Experimental study of periosteal osteoblasts coculture with freeze-dried
      demineralized bone matrix].
AB  - OBJECTIVE: To investigate the feasibility of freeze-dried demineralized bone
      matrix (FDBM) as scaffold material in bone tissue engineering. METHODS:
      Osteoblasts which were isolated from cranial periosteum of New Zealand rabbits
      were cultured as the seeding cells, then the cells were cocultured with
      heterogenous FDBM in vitro. The cell-material complex was observed under phase
      microscope, light microscope and electronic scanning microscope in order to
      evaluate the interaction between cells and FDBM. RESULTS: Eight hours after
      coculture, the osteoblasts adhered to FDBM scaffolds. Seven days later, the
      osteoblasts differentiated and proliferated in FDBM network. Extracellular matrix
      was secreted and calcium nodes were formed among osteoblasts. CONCLUSION: FDBM is
      a good scaffold material for the bone tissue engineering.

PMID- 11826656
TI  - [Treatment methods of body surface hemangioma].
AB  - OBJECTIVE: To discuss the methods selection on treatment of body surface
      hemangioma. METHODS: From February 1983 to March 2001, 265 patients with
      different types of body surface hemangioma were treated with prednisone in 94
      cases, laser in 102 cases, and plastic surgery operation in 69 cases
      respectively. RESULTS: Followed up 6 months to 15 years, 70 cases with prednisone
      treatment were cured (74.5%), which meaned the hemangioma was totally removed and
      no recurrence in 6 months follow-up, 51 cases with laser treatment were cured
      (50%), while in the plastic surgery operation group, the cure rate was 98.6% (68
      cases). CONCLUSION: Treatment with prednisone, laser or plastic surgery operation
      are all effective to body surface hemangioma and proper treatment method should
      be selected according to different period and different type of hemangioma to
      improve the therapeutic effectiveness.

PMID- 11826658
TI  - [Experimental study of the transferred keratinocytes transplanted on
      biomembrane].
AB  - OBJECTIVE: To search an ideal carrier of transferred keratinocytes for
      transplantation. METHODS: The transferred keratinocytes were seeded on the
      surfaces of the artificial dermis and the silicone membrane and cultured in vitro
      for 2 weeks. The growth of the keratinocytes was observed by microscope and
      scanning electron microscope. RESULTS: The keratinocytes implanted on the
      artificial dermis began to rupture and died after 2 to 3 days. While the
      keratinocytes adhered well on the surface of silicone membrane with pseudopodia
      formation after 1 week under scanning electron microscope, and the cells kept
      normal morphological and proliferative properties 2 weeks later. CONCLUSION: The
      silicone membrane can be applied as an useful carrier for the keratinocytes
      transplantation.

PMID- 11826659
TI  - [Vascular endothelial growth factor--fundamental research and experimental study
      in plastic surgery].
AB  - OBJECTIVE: To review the fundamental research and the experimental study of
      vascular endothelial growth factor (VEGF). METHODS: The laboratory information
      and experimental study of VEGF were extensively reviewed. RESULTS: VEGF, as a
      mitogen specifically for endothelial cells, could strongly stimulate angiogenesis
      as well as vascular permeability, especially in hypoxia state. Experimentally,
      survival area and viability of flaps could be increased significantly when
      exogenous VEGF was applied in the form of protein or cDNA. CONCLUSION: VEGF
      provides a new way for therapeutic angiogenesis in reparative and reconstructive
      surgery.

PMID- 11826660
TI  - [Reducing infarcts and strokes by lowering lipids].

PMID- 11826661
TI  - [Sleep disorders. The importance of pharmaceutical daily life].

PMID- 11826662
TI  - [Medical aspects of left handedness].

PMID- 11826663
TI  - [Bacterial antibiotic resistance from ion channels].

PMID- 11826664
TI  - [Lactose-containing drugs in lactose intolerance?].

PMID- 11826665
TI  - [The tyrosine kinase antagonist imatinib mesylate].

PMID- 11826666
TI  - [Treatment of Alzheimer's disease. The status quo].

PMID- 11826667
TI  - ["Dosis solum facit venenum" also for herbal products].
AB  - A report of severe hepatitis due to the use of material from the plant
      Chelidonium majus, reminds us that herbal products can be much more life
      threatening than many people realise. The widespread use of plants for food has
      reinforced the idea that eating plants promotes health. With the development of
      organic chemistry in the 19th century it became possible for the first time to
      purify and identify pharmacologically active plant constituents and later on to
      synthesize related compounds with an even stronger activity. The development of
      the antimalarial artemotil from Artemisia plants is a recent example. The
      activity, safety and composition of such compounds can be controlled in just the
      same manner as purely synthetic compounds. However, some people still believe
      that traditional plants are much safer and better than modern synthetic
      pharmaceuticals. The qualitative and quantitative composition of such herbal
      medicines from alternative medical sources, are not covered by public health
      legislation. Whereas phytotherapists consider plants to be a source of useful
      drugs, regular physicians maintain that the composition of a preparation and not
      the provenance, determines its effects.

PMID- 11826668
TI  - [Free fatty acids: mediators of insulin resistance and atherosclerosis].
AB  - Free fatty acids (FFAs) are involved in the transportation of energy; in the
      postprandial phase to the peripheral tissues and in the postabsorptive phase from
      the adipose tissue to the liver. In the postprandial phase, FFAs are mainly
      derived from hydrolysis of triglyceride-rich particles like chylomicrons and very
      low-density lipoproteins (VLDL). The flux of FFAs is directed to peripheral cells
      such as adipocytes and muscle cells. In the postabsorptive period, FFAs are
      transported to the liver after being released from intracellular storage in the
      adipocytes. Complement component 3 (C3) plays an important role in the uptake of
      free fatty acids by the peripheral cells and their esterification to
      triglycerides. Since C3 is also involved in the pathogenesis of the insulin
      resistance syndrome, and since a deviant FFA metabolism with an increased FFA
      flux to the liver may induce insulin resistance, it is hypothesized that C3 may
      form the missing link between FFA metabolism and insulin resistance. In addition,
      recent studies have increasingly indicated that atherosclerosis is in fact an
      inflammation-based process involving complement-dependent responses, in which
      FFAs seem to play a role in the complement-dependent pathway. It has recently
      become apparent that FFAs have a regulatory function in the transcription of DNA,
      in relation to lipoprotein metabolism. This is where PPAR-gamma and PPAR-alpha
      agonists ('glitazones' and fibrates respectively) are active (PPAR is an
      abbreviation for peroxisome proliferation activating receptor). Glitazons may
      play an important role in the treatment of insulin resistance and related
      disorders. Acquiring more knowledge about the relationship between complement and
      FFA metabolism may increase our understanding of these processes and provide
      openings for the development of new antiatherogenic strategies.

PMID- 11826669
TI  - [Drug-induced akathisia].
AB  - Akathisia (restlessness and characteristic movements of the legs) is one of the
      most disagreeable extrapyramidal side effects and often causes non-compliance.
      Dopamine blocking agents such as antipsychotics and antiemetics, may induce
      akathisia. Particular care must be taken to distinguish akathisia from psychotic
      agitation and restless legs. The prevalence of akathisia in patients using
      classical antipsychotics is 20-30% and for users of clozapine, olanzapine and
      quetiapine (atypical antipsychotics) it is lower. Risk factors are a high dosage
      of antipsychotics, akathisia in a previous treatment, and diabetes mellitus. The
      treatment of akathisia starts, if possible, with the antipsychotic being
      withdrawn or the dose administered being lowered. Another treatment possibility
      is switching to clozapine, olanzapine or quetiapine, or adding a beta-blocking
      agent, an anticholinergic or mianserin.

PMID- 11826670
TI  - [Diagnostic image (72). An adult woman with coarsening of the face. Acromegaly].
AB  - A 45-year-old woman with acromegaly went into remission after pituitary surgery.

PMID- 11826671
TI  - [Predictive value of chills in patients presenting with fever to urgent care
      department].
AB  - OBJECTIVE: To ascertain the correlation between chills, bacteraemia, infection
      type and clinical progress in patients presenting with fever to the casualty
      department. DESIGN: Prospective, descriptive. METHOD: Anamnestic, clinical and
      microbiological data were registered from patients with fever (> 38.2 degrees C
      rectal) presenting to the Casualty Department of the Leiden University Hospital
      and the Bronovo Hospital, in the period 1 February 1994-31 July 1995 respectively
      1 February 1996-31 July 1997. RESULTS: A total of 764 patients (424 men and 340
      women; median age: 66 years) were included in the study. A chill was reported by
      270 patients (35%). Bacteria were isolated from the blood culture in the case of
      141 patients (18%). The relative risk (RR) for bacteraemia in the case of a chill
      was 2.8 (95% CI: 2.1-3.8); the positive predictive value of a chill for
      bacteraemia was 31% and the negative predictive value 89%. For 683 (89%) of the
      764 patients the cause of the fever was probably or certainly an infection, which
      was mostly pulmonary (319 patients; 42%) or urogenital (112 patients; 15%) in
      origin. The positive predictive value was 24% for patients with respiratory tract
      infections and 48% for patients with urinary tract infections. Mortality occurred
      in the case of 62 patients (8%) after a median admission period of 11 days. The
      patients who died were older than the patients discharged (p < 0.01) and there
      was a statistically significant correlation between mortality with bacteraemia
      (RR: 1.1) and serious comorbidity (RR: 6.1). CONCLUSION: There was a strong
      correlation between the chill indicated in the anamnesis and bacteraemia,
      especially in patients with a urinary tract infection. Bacteraemia, advanced age
      and serious comorbidity were unfavourable prognostic factors.

PMID- 11826672
TI  - [Acute hepatitis after use of a herbal preparation with greater celandine
      (Chelidonium majus)].
AB  - A 42-year-old woman developed jaundice due to acute hepatitis several weeks after
      ingestion of a herbal preparation containing greater celandine (Chelidonium
      majus) and curcuma root, which had been prescribed by an alternative therapist
      due to a skin complaint. After the medication had been withdrawn, clinical
      recovery was rapid and the hepatic functions returned to normal within 2 months.
      The hepatitis was ascribed to the known hepatotoxic effects of C. majus. In view
      of the increasing popularity of herbal remedies, greater awareness of side
      effects, such as hepatotoxicity, is needed. Quite a number of herbal preparations
      carry the risk of liver damage. The supposed clinical effectiveness of herbal
      remedies does not seem to always outweigh the potential risks. In the event of
      non-clarified liver function disturbances the ingestion of supposedly harmless,
      but potentially hepatotoxic, herbal products should be considered.

PMID- 11826673
TI  - [STI571: a new dimension in the treatment of chronic myeloid leukemia].
AB  - Three patients suffering from chronic myelogenous leukaemia (CML), a 36-year-old
      woman in blast crisis, and a 64-year-old woman and a 60-year-old man in the
      chronic phase, participated in a clinical trial with STI571, a recently developed
      tyrosine kinase inhibitor with relative specificity for the BCR-ABL kinase. In
      all three patients, complete haematologic remission occurred within 2 months of
      the treatment being initiated. Subsequently the patient in blast crisis underwent
      allogeneic stem-cell transplantation. For the second patient, who had experienced
      many side effects with the standard treatment, STI571 led to a better quality of
      life. The third patient reached complete cytogenetic remission after 3 months of
      treatment. The development of STI571 is a major breakthrough in the treatment of
      CML. There are few side effects and the short-term results are excellent in
      specific patient categories. Further research is needed to establish the eventual
      role of STI571 in the treatment of CML.

PMID- 11826674
TI  - [Should patients with a prosthetic joint be given antibiotic prophylaxis for a
      (suspected) bacterial infection].

PMID- 11826675
TI  - [Breast cancer screening lacks effectiveness].

PMID- 11826676
TI  - [Cerebral white matter lesions in the elderly: vascular risk factors and
      cognitive consequences].

PMID- 11826677
TI  - [PEG-catheter: a trap without escape?].

PMID- 11826678
TI  - [PEG-catheter: a trap without escape?].

PMID- 11826679
TI  - [Letters of condolence to the relatives of patients].

PMID- 11826680
TI  - ['Caring: always'; physicians' expression of condolences to the relatives of
      patients].

PMID- 11826681
TI  - ['Caring: always'; physicians' expression of condolences to the relatives of
      patients].

PMID- 11826682
TI  - ['Caring: always'; physicians' expression of condolences to the relatives of
      patients].

PMID- 11826683
TI  - [Physical diagnostics--bimanual vaginal examination].

PMID- 11826684
TI  - [Devastating community-acquired Staphylococcus aureus bacteremia].
AB  - Three patients, two men aged 52 and 62 years and a woman aged 83 years,
      experienced non-specific flu-like symptoms for a few days but subsequently
      developed a complicated disease with multiple metastatic infections and
      endocarditis due to bacteraemia. Only the man aged 62 years had a port of entry,
      a finger wound. Two patients died. Community-acquired S. aureus bacteraemia is a
      much more serious disease than nosocomial bacteraemia. The community-acquired
      bacteraemia is characterised by the absence of a primary focus and non-specific
      flu-like symptoms in the beginning. This results in a long-duration bacteraemia
      with a high incidence of metastatic infections, endocarditis and a high mortality
      rate. A multidisciplinary treatment approach with a careful search for and
      treatment of endocarditic and metastatic infections in combination with long
      duration, high-dose antibiotics is warranted.

PMID- 11826685
TI  - Health related quality of life in sinonasal disease.
AB  - Objective measurements of sinonasal disease have proved difficult to standardise
      and correlate poorly with the severity of symptoms. Quality of life, which has
      been defined as the gap between expectation and experience allows the impact of
      disease to be quantified thus enabling comparison of different diseases and
      enabling examination of therapeutic response. A range of generic and disease
      specific questionnaires have been developed of varying complexity. These have
      been applied to a range of sinonasal conditions including allergy, infection and
      neoplasia. With increasing refinement they may become the main primary outcome
      measures in both clinical trials and practice.

PMID- 11826686
TI  - Leukotriene receptor antagonists: clinical potential in allergic rhinitis.
AB  - Leukotrienes are potent pro-inflammatory mediators that have been shown to play a
      prominent role in the pathophysiology of asthma and associated allergic disorders
      including allergic rhinitis (AR) and atopic dermatitis (AD). In the treatment of
      these disorders, topical corticosteroids (TCS) are currently the most important
      anti-inflammatory agents, however, long-term application of TCS is associated
      with side-effects. Moreover, corticosteroids appeared not to inhibit the release
      of leukotrienes in humans in vivo. Therefore, leukotriene receptor antagonists
      (LTRAs) have been introduced into clinical practice and these specific oral drugs
      are currently registered as additive therapy in mild to moderate persistent
      asthma not controlled by inhaled corticosteroids. As for other allergic
      disorders, including AR, until recently only a few placebo-controlled studies
      with LTRAs have been performed. These (preliminary) data provide a basis for
      optimism, but clearly more long-term studies are needed to evaluate their
      clinical effectiveness, especially as add-on therapy.

PMID- 11826687
TI  - Assessing the quality of life for patients with chronic rhinosinusitis using the
      "Rhinosinusitis Disability Index".
AB  - Quality of life studies are increasingly being use as the primary outcome measure
      in chronic rhinosinusitis. The Rhinosinusitis Disability Index (RSDI) is a
      recently designed validated measure that has not been used in clinical studies.
      We have used the RSDI on 53 patients with chronic rhinosinusitis and compared the
      results to their endoscopic score and self-rated symptom score. Our data showed
      that the mean total quality of life score was 42 with a range of 5 to 69 (SD 17).
      The means of the functional, emotional and physical domains were 13 (range 0 to
      27, SD 6), 13 (range 0 to 25, SD 7) and 16 (range of 2 to 32, SD of 7)
      respectively. There was no correlation between endoscopic score and either the
      patient's self-rated symptom score or RSDI score. The correlation between the
      self-rated symptom score and total quality of life score was significant (p =
      0.02). Various areas of the patients' quality of life were shown to be affected
      by chronic rhinosinusitis.

PMID- 11826688
TI  - Correlation of nasal morphology and respiratory function.
AB  - In order to investigate the fluid dynamic preconditions that guarantee a
      sufficient contact of air with nasal mucosa, we studied flow patterns in modified
      "Mink's boxes" and in nasal models. As a result, the nose can be divided into 1)
      a functional area, i.e. area of turbinates, 2) an inflow area, i.e. vestibulum,
      isthmus and anterior cavum and 3) an outflow area, i.e. posterior cavum, choanae
      and epipharynx. The vestibulum is shaped like and acts as a bend, redirecting air
      to the cavum, and as a nozzle, reducing turbulence. With its concavely curved
      shape, the isthmus facilitates equal distribution of air throughout the entire
      area of the turbinates. The anterior cavum acts as a diffuser, where turbulence
      increases and velocity decreases. In the slit-like space of the area of
      turbinates, the flow behavior is determined by flow dynamics in the inflow area.
      The structure elements of the outflow area are similar to those of the inflow
      area but lined up in an inverse order.

PMID- 11826689
TI  - Temperature and humidity profile of the anterior nasal airways of patients with
      nasal septal perforation.
AB  - INTRODUCTION: The most frequent symptoms of patients with nasal septal
      perforations are crusting and bleeding. The aim of this study was to determine
      the influence of septal perforations on temperature and humidity of the anterior
      nasal airways. PATIENTS AND METHODS: Intranasal temperature and humidity were
      measured in the nasal valve area, the anterior turbinate area and in the
      nasopharynx during normal respiration. A miniaturized thermocouple and a humidity
      sensor were used for continuous detection. Ten patients with septal perforations
      were enclosed into the study. The results were compared to matched healthy
      control subjects. RESULTS: There were no significant differences of the
      temperature and humidity values between the left and right side of the nasal
      cavity in each study group. At the end of inspiration, nasal air temperature did
      not differ significantly between the two study groups. The humidity values at the
      end of inspiration were statistically significantly lower in the patient group.
      CONCLUSIONS: Nasal septal perforations seem to be related to lower humidity in
      the anterior nasal airways during inspiration. Reduced humidity may contribute to
      crusting as a main symptom.

PMID- 11826690
TI  - Transsphenoidal surgery utilizing computer-assisted stereotactic guidance.
AB  - Computer-assisted guidance technology represents the next step in the application
      of stereotactic techniques to skull base surgery. Use of this 3-D technique
      reduces operative time and complications as the technique allows a more direct
      approach with precise real-time anatomical guidance. We present seven cases of
      transsphenoidal parasellar surgery where this technique has been employed. The
      pathology included lesions of the sella turcica, parasellar region and the
      petrous apex.

PMID- 11826691
TI  - Assessing the reproducibility of nasal spirometry parameters in the measurement
      of nasal patency.
AB  - The reproducibility of nasal spirometry was assessed in ten subjects at two
      visits. Topical nasal decongestion was applied to minimise mucosal variation.
      Eleven parameters of flow volume were measured. Data analysis using Spearman's
      rank correlation coefficients revealed peak inspiratory flow rate (PIFR) followed
      by forced expiratory volume in first one second (FEV1) to be the most
      reproducible measures, yielding significance values of < 0.05. For all other
      spirometric parameters significance was not reached. Analysis revealed that using
      a naso-pulmonary index (a ratio of nasal to pulmonary flow) was detrimental to
      reproducibility. We conclude that future nasal spirometric studies should use
      PIFR and FEV1 as their derived variables of flow-volume loops in the assessment
      of nasal patency, and the naso-pulmonary index is of no value.

PMID- 11826692
TI  - Evaluation of powered instrumentation in out-patient revisional sinus surgery.
AB  - A feasibility study was carried out to prove the benefits of powered
      instrumentation, i.e. microdebrider in revisional surgery under local anaesthesia
      of chronic sinusitis in out-patients. Acceptance by the patients was investigated
      by questionnaire. Out-patient surgery is well tolerated by the majority (79.2%)
      of patients. Ninety-four percent would undergo the treatment again if necessary.
      An operation under general anaesthesia could be avoided in the cases we submitted
      to investigation. The cost-effectiveness of the method is thus an important
      consideration, despite calculating high prime costs and rather expensive,
      expendable instrumentation. Special consideration is attributed to a new feature
      added to the debrider device. To improve out-patient care, we developed an
      integrated electrocoagulation unit which supplements the microdebrider. It proved
      to be effective and easy to use. Bleeding was reduced to a minimum. Hence, nasal
      packing could be avoided in all out-patient cases. The possibility of causing
      severe complications using the microdebrider-technique is not eliminated as was
      shown in the anatomical specimens. Based on our experience, reduction of strong
      bony structures is subject to limitations at present. We therefore recommend the
      use of microdebriders for soft tissue manipulations, especially in revisional
      surgery. The microdebrider proved to be a significant advantage in out-patient
      surgery for recurrent sinusitis.

PMID- 11826693
TI  - Possible role of plasminogen activator in the occurrence of profuse watery
      rhinorrhea after topical application of epinephrine to the nasal mucosa.
AB  - Epinephrine and lidocaine have been used for the diagnosis and treatment of nasal
      diseases. However, watery rhinorrhea and frequent sneezing occur in many patients
      after topical application of these drugs to the nasal mucosa. This study was
      aimed at characterizing these side effects, and developing a means to prevent
      such side effects. A questionnaire was given to each patient who complained of
      side effects after treatment with epinephrine and lidocaine, and the answers were
      analyzed with respect to the occurrence and features of the symptoms after the
      treatment. Eosinophil and mast cell numbers were determined in nasal smears from
      the patients with side effects. These side effects were different from rhinitis
      medicamentosa and allergic rhinitis, and were due to epinephrine, not to
      lidocaine or to the preservatives in the epinephrine. Tranexamic acd, an
      inhibitor of plasmin, was effective in blocking the side effects.

PMID- 11826694
TI  - Delivery of nasal drops to the middle meatus: which is the best head position?
AB  - BACKGROUND: Chronic sinusitis and intranasal polyps require long-term topical
      drug therapy. The issue of drug delivery to the critical area of the middle
      meatus is rarely addressed. AIM: The aim of this study was to compare the
      delivery of drops to the middle meatus using four different head positions
      (Mecca, Mygind, Ragan and Head back). The study also assessed the discomfort with
      each position whilst administering the nasal drops. METHODS: Nine nostrils in
      five healthy volunteers were studied to compare the delivery of drops to the
      middle meatus using the four different head positions. A neurosurgical patty was
      placed under direct vision in the middle meatus using a rigid nasendoscope. Six
      drops of dyed-saline were administered into each nostril. Upon removal, a
      quantitative assessment was made of the amount of dye absorbed and discomfort
      assessed. The direction of flow of the nasal drops in the nose was also
      demonstrated. RESULTS: The 'Mygind' and 'Ragan' positions were superior to the
      'Mecca' and 'Head back' positions in delivery of drops to the middle meatus. The
      'Mecca' position was the most uncomfortable. CONCLUSION: We recommend that the
      'Mygind' or 'Ragan' position should be used for nasal drop administration.

PMID- 11826695
TI  - Blood loss reduction during laser turbinectomy.
AB  - The use of a combination of topical and injected anaesthetic and vasoconstrictive
      agents is widely applied in rhinological practice. To prepare the nose prior to a
      laser inferior turbinectomy under combined general and local anaesthetic, we
      routinely spray the nose with 1:1000 epinephrine and inject 2% xylocaine with
      1:80.000 epinephrine into each inferior turbinate. With the current climate
      tending towards evidence based medicine, we were keen to show that our technique
      of pre-operative nasal preparation was effective. A randomised, double blind,
      prospective study was carried out, with patients acting as their own control. We
      found that the injection of 2% xylocaine with 1:80.000 epinephrine did not confer
      any additional benefit, in terms of blood loss or post-operative pain, in the
      treatment of these patients. The inferior turbinate that was injected bled more
      during the procedure than the non-injected side; there was no difference in post
      operative discomfort between the 2 sides.

PMID- 11826696
TI  - Leiomyoma of the nasal septum.
AB  - Leiomyoma is a benign myogenic tumor that may develop wherever smooth muscle is
      present. It occurs commonly in the uterus, skin, and gastrointestinal tract and
      is rare within the nasal cavity. Only three of twenty-four reported cases of
      sinonasal leiomyoma have been found to originate from the nasal septum. Treatment
      of choice for these neoplasms is surgical excision. We present two cases of nasal
      septal leiomyoma. Unique features discussed include recurrence of one neoplasm
      and the technique used to endoscopically repair a cerebrospinal fluid leak
      resulting from resection of the neoplasm.

PMID- 11826697
TI  - An extensive maxillary pneumosinus dilatans.
AB  - Pneumosinus dilatans is a very rare lesion. An aggressive case of a maxillary
      pneumosinus dilatans is presented. CT and MRI showed that the lesion involved the
      orbit, cheek and nasal cavity. A reopening to the affected maxillary sinus as a
      FESS procedure was performed with success.

PMID- 11826699
TI  - ICD: effective but not without complications.

PMID- 11826698
TI  - Implantable cardioverter-defibrillator: beyond efficacy.
AB  - OBJECTIVES: The introduction of the implantable cardioverter-defibrillator was a
      very important advance in the treatment of malignant ventricular arrhythmias.
      However, its use is associated with some possible adverse events, which should be
      taken into consideration when a patient is proposed for implantation. These
      complications may occur early after implantation and be associated with the
      procedure itself, or they may be late complications, usually associated with the
      device or the arrhythmia. It was our objective to assess the incidence of these
      complications in our population of patients. POPULATION AND METHODS: We describe
      the complications found in 98 patients (55.9 +/- 13.9 years, 89% male) with an
      implantable cardioverter-defibrillator and compare our results with the incidence
      of complications described by other authors. RESULTS: We found complications
      associated with the presence of the implantable cardioverter-defibrillator in 32%
      of patients. The most frequent complication was inappropriate shocks in 13%. The
      presence of infection was detected in 4%, lead insulation faults in 5%, need for
      lead extraction in 2%, repositioning in 1% and re-establishment of the connection
      with the generator in 2%. In 5% of patients, there was inefficacy of the device,
      3% due to non-detected ventricular tachycardias (slow tachycardias) and 2% due to
      electrical storms. There was syncope in 2% of patients. The total mortality in a
      2.9 +/- 1.9 year follow-up was 13% (sudden death in 3%). CONCLUSIONS: Major
      complications associated with implantable cardioverter-defibrillators were in our
      experience relatively rare, our results agreeing with those of other centers.

PMID- 11826700
TI  - Cardiac rhabdomyomas presenting in neonates.
AB  - Rhabdomyoma is the most common cardiac neoplasm in neonates. Spontaneous
      regression of such tumors is common, particularly with smaller lesions, followed
      by resolution of symptoms. Because most of the tumoral masses regress
      spontaneously, treatment should primarily be symptomatic, while surgical removal
      is required only in life-threatening situations. Tuberous sclerosis is found in
      half of the patients with rhabdomyomas. AIM: The aim of our work was to analyze
      the cases of rhabdomyoma with neonatal presentation in our hospital. METHODS: A
      retrospective review was performed of the hospital records (cardiovascular
      examination, radiologic and echocardiographic findings, association with tuberous
      sclerosis, treatment and follow-up) of all neonates admitted, during the last 12
      years, with the diagnosis of rhabdomyoma. RESULTS: Six patients were found. All
      diagnoses were established during the first month of life. One third of our
      population had associated tuberous sclerosis. In three cases the tumors were
      multiple and the preferential location was the left ventricle. In only one case
      was surgical removal indicated because of the presence of life-threatening
      symptoms but the infant's parents refused consent for the procedure. All the
      children had regression of the tumoral masses. CONCLUSIONS: The natural history
      of rhabdomyomas is one of spontaneous regression with surgical excision being
      recommended only in the presence of life-threatening symptoms.

PMID- 11826701
TI  - [Uncomplicated acute myocardial infarction -- when should the patient be
      discharged?].
AB  - INTRODUCTION AND OBJECTIVES: Hospital discharge on day 10 after acute myocardial
      infarction (AMI) is still frequent in our hospital. The present study aims at
      evaluating the occurrence of cardiac events on day 5, 7 and 10, in patients with
      AMI who had an uncomplicated course for 72 hours after thrombolysis, as well as a
      cost-effectiveness analysis on an earlier discharge. METHODS: We retrospectively
      studied consecutive patients admitted with AMI for a period of 5 years, submitted
      to thrombolysis who suffered no events (recurrent ischemia, reinfarction,
      coronary revascularization, heart failure, arrhythmias implicating electric
      cardioversion or dysfibrilation, pacemaker or death) within the first 72 hours (n
      = 128; 101 males and 27 females, mean age 64.1 +/- 12.8). Patients were divided
      into two groups, with no events occurring by discharge (group I, n = 119) or with
      events between 72 hours and discharge (group II, n = 9). The latter were
      subdivided according to whether events occurred between 72 hours and day 5,
      between days 6 and 7 or between 8 and 10. RESULTS: Group I and II were not
      significantly different regarding vascular risk factors, prior coronary disease
      and infarction location. Group I was mainly constituted of males, younger than
      those in group II and with preserved systolic LV function. Between 72 hours and
      discharge, there were no events in 93% of the patients (119) and events occurred
      in 7% (9 patients). Two cases of cardiac events occurred until day 5 (1.6%) one
      angina and one death, two patients with complications between days 6 and 7
      (1.6%), both heart failure, and 5 patients suffered events after day 7 (4%), 3
      angina and 2 deaths. Dead patients (3 cases--2.3%) were older, had prior AMI,
      mostly with unpreserved systolic LV function and prior ischemic heart disease.
      All of them had sudden death. The most frequent non-fatal complications were
      recurrent ischemia and heart failure. CONCLUSIONS AND IMPLICATIONS: In patients
      with AMI who had an uncomplicated course for 72 hours after thrombolysis, the
      risk of cardiac events by the 10th day is low. It occurs randomly in time. In
      this group of patients it seems of no effectiveness to lengthen hospitalization.
      An earlier discharge may be advantageous since it does not significantly increase
      the risk that a longer hospitalization could prevent.

PMID- 11826702
TI  - [Type B natriuretic peptide in the diagnosis of heart failure with preserved
      systolic function].
AB  - BACKGROUND: Heart failure (HF) with preserved left ventricular systolic function
      (LVSF) is observed in up to 50% patients with HF. There is no consensus on non
      invasive diagnosis of this entity. OBJECTIVE: Evaluation of B-type natriuretic
      peptide (BNP) in the diagnosis of HF with preserved left ventricular systolic
      function. DESIGN: Prospective study. PATIENTS: One hundred and seventy-six
      consecutive patients with suspected HF were evaluated. Patients were classified
      as having HF with preserved LVSF, if they had symptoms and signs of HF, an
      ejection fraction greater than 40% and an abnormal Doppler pattern of the mitral
      inflow or atrial fibrilation and no other causes for the symptoms. All patients
      had a 12-lead EKG, chest roentgenogram, simple spirometry, M-mode and 2D
      echocardiogram with pulsed Doppler study of transmitral inflow and determination
      of plasma BNP levels. RESULTS: Of the 176 patients, 65 had ejection fraction
      greater than 40%. Of these patients 46 were classified as having HF with
      preserved LVSF and 19 as not having HF. Patients with HF and preserved LVSF were
      older, had a higher systolic blood pressure (SBP), less pathologic Q waves on ECG
      and higher left ventricular ejection fraction and plasma BNP than patients
      without HF. Multivariate analysis revealed that BNP and SBP were independently
      associated with the diagnosis of HF. The accuracy of BNP in the diagnosis of HF
      with preserved LVSF evaluated by the area under the receiver operating
      characteristic curve was 0.94. CONCLUSION: These results suggest that the
      measurement of BNP levels can help clinicians in the diagnosis of HF with
      preserved LVSF. Whether BNP levels might be used in clinical practice as a test
      for the diagnosis of HF with preserved LVSF is a question that merits further
      studies.

PMID- 11826704
TI  - [Primary mesothelioma of the pericardium: a clinical case].
AB  - We describe a 33-years-old male patient, presenting with progressive right heart
      failure. After evaluation, the hypothesis of effusive-constrictive pericarditis
      was considered. Medical therapy was initiated with no clinical benefit. On the
      15th day after admission he was proposed for surgical intervention. The
      intraoperatory examination revealed a thick pericardium adhering to the
      epicardium without a clear separation between them. Complete resection was
      technically impossible. The postoperative course evolved with worsening heart
      failure and development of renal failure requiring hemodialysis. A diagnosis of
      primary pericardial mesothelioma was made after histological evaluation. The
      patient died 8 days after surgery despite all efforts at hemodynamic
      compensation. Despite its rarity, this diagnosis should be considered in cases
      with rapid evolution of constrictive or effusive-constrictive pericarditis. The
      prognosis for pericardial mesothelioma is poor due to its late diagnosis, the
      difficulty of surgical excision and poor response to radio- or chemotherapy.

PMID- 11826703
TI  - [Constrictive pericarditis: an early diagnosis?].
AB  - The authors report a case study of a 73-year-old male, with signs of right-sided
      heart failure with 6 months of evolution. It was constrictive pericarditis,
      without radiologic, echocardiographic and magnetic resonance imaging
      manifestations, diagnosed on the basis of the clinical situation and hemodynamic
      evaluation during cardiac catheterization. The authors suggest that the lack of
      imagiologic manifestations might have been the result of an early diagnosis,
      before the development of the classic picture. Pericardiectomy, performed with
      success, was followed by resolution of the heart failure. It was not possible,
      histologically, to draw conclusions about the etiology. The development of mitral
      regurgitation after pericardiectomy has enriched this case with an unusual, but
      previously described, complication of this type of surgery.

PMID- 11826705
TI  - [Basic principles of selection and use of diagnostic tests: analysis of the
      results of diagnostic studies].
AB  - In clinical practice, in order to design and implement a specific therapeutic
      plan, as well as communicating an appropriate prognosis, the doctor needs to
      establish a precise diagnosis of the condition. Sometimes all one needs is a
      clinical impression. More often, however, the definition of an accurate diagnosis
      will need the interpretation of specific diagnostic tests as well. The rational
      use of diagnostic tests in cardiology--whether laboratorial or imagiologic-
      should be based on three factors: 1) validity of the study results about the
      test; 2) diagnostic properties of the test and 3) applicability of the test in
      the clinical setting. The rational use and correct interpretation of diagnostic
      tests are based on these three factors. In this article we present the basic
      principles concerning the validity of the results from the study that defined the
      specific test, and what level of evidence that constitutes. Other articles will
      address diagnostic properties of tests (sensitivity, specificity, positive and
      negative predictive values, likelihood ratios) as well as the applicability of
      the test in clinical practice.

PMID- 11826706
TI  - A case of anatomically corrected transposition of the great vessels.

PMID- 11826707
TI  - [Effects of the dual endothelin-receptor antagonist bosentan in patients with
      pulmonary hypertension: a randomized placebo-controlled study].

PMID- 11826708
TI  - [Juvenile breast hypertrophy: analysis of long-term results of reductive
      mammoplasty].
AB  - Reduction mammaplasty has now become routine surgery with good results in middle
      aged women. However the scars it leaves, its psychological and functional
      (breastfeeding) impact could limited its indications in teenage girls. AIM: The
      purpose of our study was to report the long-term results of reduction mammaplasty
      in teenage girls and to assess their consequences. MATERIAL AND METHODS: We
      conducted a retrospective study of 65 reduction mammaplasty carried out between
      1981 and 1997 in 15 to 17 years old girls. The study was based on data in their
      medical records and answers to a questionnaire which was sent to each patient.
      RESULTS: Average followup was 8.1 years. The reduction technique with superior
      pedicle were mainly used. Average breast tissue excised was 1050 g. Minor
      complications occurred in three cases. Eleven revisions had to be carried out
      with 1.6 years on average after primary surgery. The psychological and functional
      complaints observed preoperatively disappeared in more than 90% of the cases. In
      over 80% of the cases the patients were pleased or very pleased with the shape,
      the volume kept and the symmetry. Scars were well accepted in 83% of the cases.
      Seventeen women were given birth to 25 children. Five of whom breast-fed their
      babies, while six refused because of their breast surgery history. Although
      information about breast-feeding after such surgery is systematically given, 41
      women claimed they had not received it. CONCLUSION: Reduction mammaplasty is
      reliable in teenage girls. Patients are generally satisfied and the remaining
      scar is well accepted. Breast-feeding is possible after this surgery and
      information on that point ought to be better developed.

PMID- 11826709
TI  - [Large ventral hernia in tropical countries: etiology and results of treatment
      with the Judd technique].
AB  - Large ventral hernia is a most common pathology in surgical practice in tropical
      countries. We reported 67 cases of large ventral hernia with mean diameter about
      11.7 cm. There were 41 women and 26 men. It was incisional hernia in 49 cases;
      recurrent ventral hernia in ten cases (after first repair six cases and after the
      second repair in four cases). Ventral hernia occured in 18 women after many
      pregnancies (mean of five pregnancies in ten years): this etiology of ventral
      hernia is the particularity of our practice; rarely in developed countries where
      number of pregnancies by women varied from two and where the women had means to
      abdominal wall reeducation. Another factor was excessive weigh: in our country,
      woman must take some many kilogrammes after pregnancy by traditional practice.
      Without means in our hospital, preoperative exams were limited to detect and
      treated cardiorespiratory diseases. All patients had an repair of their ventral
      hernia by autoplasty like described by Judd completed by another layer with the
      same ligature. Postoperative time was marked by wound sepsis (11 cases), dyspnea
      (ten cases), intestinal pseudo-obstruction (eight cases) and three patients were
      died (failure of respiratory system in two cases and cardiac failure in one
      case). After 18 months there were seven recurrent ventral hernia, all in
      incisional hernia. Judd's autoplastic technic is an efficacy technic in primitive
      ventral hernia or for the first repair of incisional ventral hernia. Preoperative
      management must concern all respiratory problems and their treatment.

PMID- 11826710
TI  - [Cultured epidermis for the treatment of severe burns. A 2-year study (18
      patients)].
AB  - AIM OF THE STUDY: For fifteen years, Edouard Herriot Burn Center has been using
      cultured epidermis provided by an hospital Laboratory. This means of production
      results in great freedom for their application compared with the centers who have
      to buy the cultured epidermis. In order to evaluate our clinical results, a two
      year study has been performed. MATERIAL AND METHODS: Eighteen patients suffering
      acute burns were concerned. The average burned area was 68% of the total body
      surface (range 49 to 88). The average age was 31.6 years, ranging from 1 to 58,
      including two children. Even autologous or allogenic epidermis was used. In our
      series cultured epidermis was grafted according four different strategies. It was
      the preparation of the wound bed by skin allografts, the association of widely
      meshed auto-graft with cultured epidermis, the stimulation of the healing of
      extensive deep second degree burns with allogenic epidermis, and the coverage of
      skin auto-graft donor sites. RESULTS: Two patients died. For the survivors, the
      average hospital stay was 60 days (range 22 to 90), and on average 70 days over
      70% TBSA burns. Cultured epidermis allowed the definitive coverage of 17% of the
      total body surface of the patients. This study supports the importance of a
      careful preparation of the patient for the engraftment of cultured epidermis.
      CONCLUSION: In our opinion, in spite of the difficulties of handling of cultured
      epidermis, they represent a precious means of coverage for the rapid and
      definitive healing of extensive burns over 70% TBSA.

PMID- 11826711
TI  - [Recurrence of finger tendon giant cell tumors after excision through a "shark
      teeth" approach. Report of 25 cases].
AB  - Local recurrences after excision of a giant cell tumor of the tendon sheath are
      classically related to incomplete excision. We have review a special group of
      circumferential tumors excised through a huge approach. Twenty-six
      circumferential tumors were excised between 1985 and 1998, through a special
      incision described by the senior author. It is composed of four triangular flaps
      drawn around the finger, one dorsal, one palmar (both proximally based) and two
      lateral (distally based). Six presented already with a recurrence of previous
      operations (mean 2.5 interventions). Some anatomical neighboring structure was
      "invaded" in all except one case. However the approach allows for a
      macroscopically satisfactory excision. Twenty-five patients were reviewed by an
      independent observator after a mean follow-up of six years. Six patients (24%)
      presented a recurrence after a mean postoperative delay of 17 months. Among them
      five have been already operated (83%) and five had multiple tumors. Satisfactory
      excision does not prevent recurrence and two types of distinct tumors exist.
      Recent immunohistological studies give support to this view and such examination
      is recommended.

PMID- 11826712
TI  - [Anatomical study of the temporalis tendon. Value in temporalis lengthening
      myoplasty].
AB  - The lengthening temporalis myoplasty is indicated in long standing and congenital
      facial paralysis. Its principle is the transfer of the coronoid tendinous
      insertions onto the lip and the nasolabial fold. The knowledge of the anatomy of
      this strong and wide tendon is necessary to use successfully their anatomical
      advantages. A study of ten cadavers (20 temporalis muscles) confirmed the
      surgical anatomy found during lengthening temporalis myoplasty procedure: the
      strong tendon, when liberated from the coronoid process, is from 4 to 6 cm long.

PMID- 11826713
TI  - [Extended nasal reconstruction with forehead flap. Report of a series of 12
      adults].
AB  - The authors report a study about 12 cases of partial, total and extensive
      rhinectomy treated by a median "gingko flower" forehead flap. Technical
      adaptations are described to resolve the difficult problem of support and lining
      reconstruction. The authors compare their technique with the various other
      methods: the classical one (Converse scalping and sea-gull Millard's flaps) or
      more recent surgical solutions (distal composite flaps and expansion).

PMID- 11826714
TI  - [Adipofascial flaps of the frontal-internal part of the leg: an alternative to
      free flaps for the repair of skin loss from the knee to the ankle. Report of a
      clinical experience with 17 cases].
AB  - Leg coverage remains a difficult challenge for plastic surgeon, especially in
      certain areas. Although treatment of osteomyelitis is well established, coverage
      of bone, tendinous or hardware exposure remain controversial. In these selected
      cases, adiposofascial pedicled flaps should constitute a interesting solution.
      The multiples vascular supplies to the adiposofascial tissue of the medial side
      of the leg constitute de basis of this flap family. These condition allows an
      extreme adaptability to a wide range of defect with maximal satisfaction.

PMID- 11826715
TI  - Prepucial skin flap for reconstruction of the scrotum in Fournier's gangrene.
AB  - A new procedure for reconstructing a scrotal defect caused by Fournier's gangrene
      is described. Complete and quick coverage of the exposed testicles is important
      aesthetically and functionally. A dorsally based prepucial flap is designed, flap
      viability is ensured by an abundant blood supply and venous drainage. This
      procedure for reconstruction of ventral hemiscrotum by using a flap of prepucial
      skin in non-circumcised persons has proved effective in selected cases.

PMID- 11826716
TI  - [Corrective surgery of thoracic anomalies in Poland syndrome. General review of
      20 patients].
AB  - Breast and thoracic anomalies in Poland's syndrome, whether associated or not
      with hypoplasia of the upper limb, have no functional impairment. They present an
      important cosmetic disgrace. Several methods for correction were proposed:
      muscular transfer with or without implants. Each one has its advantages and
      drawbacks. MATERIAL AND METHODS: We operated 20 adolescents and adults with this
      deformity: 13 females and 7 males. If the inferior bundle of the pectoralis major
      was always absent, other muscular anomalies such as aplasia of the latissimus
      dorsi may complicate the corrective procedure. The choice of the treatment
      depends upon the importance of the muscular and sometimes associated costal
      aplasia, in the young girl, the breast development and in both sexes the position
      of the nipple. RESULTS: The latissimus dorsi transfer may be considered as the
      most adapted technique for the pestoralis major replacement. The results are
      often disappointing due to the secondary muscular atrophy. A composite implant
      with a part for breast reconstruction and another to fill the subclavicular gap
      gives satisfactory results but it has the hazards of implants.

PMID- 11826717
TI  - [Oto-mandibular dysplasia].

PMID- 11826718
TI  - [Annual Congress of the American Society of Aesthetic Plastic Surgery/ASAPS New
      York, 3-9 may 2001].

PMID- 11826719
TI  - Ecological impacts of arable intensification in Europe.
AB  - Although arable landscapes have a long history, environmental problems have
      accelerated in recent decades. The effects of these changes are usually
      externalized, being greater for society as a whole than for the farms on which
      they operate, and incentives to correct them are therefore largely lacking.
      Arable landscapes are valued by society beyond the farming community, but
      increased mechanization and farm size, simplification of crop rotations, and loss
      of non-crop features, have led to a reduction in landscape diversity. Low
      intensity arable systems have evolved a characteristic and diverse fauna and
      flora, but development of high input, simplified arable systems has been
      associated with a decline in biodiversity. Arable intensification has resulted in
      loss of non-crop habitats and simplification of plant and animal communities
      within crops, with consequent disruption to food chains and declines in many
      farmland species. Abandonment of arable management has also led to the
      replacement of such wildlife with more common and widespread species. Soils have
      deteriorated as a result of erosion, compaction, loss of organic matter and
      contamination with pesticides, and in some areas, heavy metals. Impacts on water
      are closely related to those on soils as nutrient and pesticide pollution of
      water results from surface runoff and subsurface flow, often associated with soil
      particles, which themselves have economic and ecological impacts. Nitrates and
      some pesticides also enter groundwater following leaching from arable land.
      Greatest impacts are associated with simplified, high input arable systems.
      Intensification of arable farming has been associated with pollution of air by
      pesticides, NO2 and CO2, while the loss of soil organic matter has reduced the
      system's capacity for carbon sequestration. International trade contributes to
      global climate change through long distance transport of arable inputs and
      products. The EU Rural Development Regulation (1257/99) provides an opportunity
      to implement measures for alleviating ecological impacts of arable management
      through a combination of cross-compliance and agri-environment schemes. To
      alleviate the problems described in this paper, such measures should take account
      of opportunities for public/private partnerships and should integrate social,
      cultural, economic and ecological objectives for multifunctional land use.

PMID- 11826720
TI  - Regional industrial ecology: examples from regional economic systems of forest
      industry and energy supply in Finland.
AB  - Industrial ecology (IE) promotes the development of industrial systems based on
      recycling of matter and cascading of energy through cooperation. In this paper,
      the local/regional industrial ecosystem approach is reflected in two examples
      from Finland. The local forest industry system is based on renewable resources,
      waste materials and energy utilisation between forestry companies, a saw-mill, a
      pulp mill, a paper mill and a forest industry power plant. Waste energy from
      electricity production is used for production of heat and process steam. Regional
      city energy supply systems in Finland are also to a large extent arranged around
      power plants that utilise waste energy. The potential of combining the forest
      industry system with the energy supply systems of cities is considered and the
      conditions for success in the Finnish case are discussed.

PMID- 11826721
TI  - Devising an integrated methodology for analyzing energy use and CO2 emissions
      from Taiwan's petrochemical industries.
AB  - Input-output modeling and multiplier analysis are used to assess Taiwan's five
      petrochemical industries, based upon their economic contribution and potential
      impacts on energy consumption and CO2 emission. In addition, a consolidated index
      system was developed for evaluating energy and economic efficiencies as well as
      targets for CO2 reduction. Results indicate that petrochemical materials (PM)
      make a major contribution to economic development, with lesser contributions from
      plastic materials (PL) and artificial fibres (AF). PM has the highest energy
      multiplier while PL has the largest induced potential for energy consumption.
      Plastic and rubber products (PP, RP) are relatively insignificant energy
      consumers. AF has the highest CO2 multiplier, and its induced potential for CO2
      emission is the most significant. The consolidated index shows that the upstream
      petrochemical industries perform rather poorly in an integrated view of economic,
      energy, and CO2 emission, and should be seen as the primary targets for CO2
      reduction. Investment of the petrochemical industries in Taiwan should be
      adjusted to improve energy efficiency, economic bases, and lower CO2 emissions.

PMID- 11826722
TI  - Environmental management in resource-rich Alberta, Canada: first world
      jurisdiction, Third World analogue?
AB  - Economic growth is frequently touted as a cure for environmental ills,
      particularly for those in Third World countries. Here we examine that paradigm in
      a case study of Alberta, Canada, a wealthy, resource-rich province within a
      wealthy nation. Through provincial-scale datasets, we examine the increasing
      pressures of the forest, petroleum, and agricultural industries upon the
      ecosystems of Alberta within management, economic, and political contexts. We
      advance the thesis that economic activity leads to environmental degradation
      unless ecosystem-based management is integrated into economic decision making.
      Agricultural lands cover 31.7%, and forest management areas leased to industry
      cover 33.4% of Alberta; both continue to increase in extent. The rate of logging
      (focused on old-growth by government policy) continues a decades-long exponential
      rise. Current Alberta annual petroleum production is 52.5 million m3 crude oil
      and 117 billion m3 of gas. As of early 1999, there were approximately 199,025 oil
      and gas wells and a conservative total of approximately 1.5-1.8 million km of
      seismic lines in Alberta. Fire occurrence data indicate no downward trends in
      annual area burned by wildfire, which may be characterized as driven by climate
      and inherently variable. When logging and wildfire are combined, the annual
      allowable cut in Alberta is unsustainable, even when only timber supply is
      considered and the effects of expanding agriculture and oil and gas activities
      are ignored. Ecosystem degradation in Alberta is pervasive and contrasts
      prominently with a high standard of living. A wealth of ecological data exists
      that indicates current resource-based economic activities are non-sustainable and
      destructive of ecosystem health yet these data are not considered within the
      economic decision making process. Given the complex, compounded, and increasing
      ecosystem perturbations, a future of unpleasant ecological surprises is likely.
      We conclude with tentative predictions as to where current trends in Alberta may
      lead if decisions biased against ecosystems continue.

PMID- 11826723
TI  - A systems approach to the evaluation of natural resource management initiatives.
AB  - Adopting a new paradigm for natural resource and environmental policy that
      emphasises continuous change, adaptation and learning demands a new approach to
      evaluation to enable improvements in the way these initiatives contribute to
      sustainable resource use. Evaluation is fundamental to identifying change,
      supporting an adaptive approach that is flexible enough to meet the challenge of
      change, and enabling learning at individual, community, institutional and policy
      levels. Based on a consideration of changing approaches to natural resource
      management (NRM) policy and observations and experiences in the practical
      assessment of on-the-ground initiatives, the authors develop a set of principles
      for evaluation in NRM that: (a) addresses evaluation from a systems perspective,
      (b) links objective to consequence, (c) considers the fundamental assumptions and
      hypotheses that underpin core policy or program objectives, (d) is grounded in
      the natural resource, policy/institutional, economic, socio-cultural and
      technological contexts of implementation in practice, (e) establishes practical
      and valid evaluation criteria by which change can be monitored and assessed, (f)
      involves methodological pluralism including both quantitative and qualitative
      methods to ensure rigour and comprehensiveness in assessment, and (g) integrates
      different disciplinary perspectives (i.e. social, economic, environmental, policy
      and technological). The paper develops a systems-based evaluation framework that
      incorporates these principles and also recognises the multiple levels and nested
      nature of NRM policy, namely: problem characterisation, policy formulation and
      intent, program logic, and on-ground implementation. Finally, we demonstrate its
      utility through application to three contrasting Australian case studies: a
      community-based Integrated Catchment Management policy implementation; a resource
      information delivery system; and the development of a Decision Support System.

PMID- 11826724
TI  - Allocating anthropogenic pollutant emissions over space: application to ozone
      pollution management.
AB  - An inventory of volatile organic compound (VOC) and nitrogen oxides (NOx)
      emissions is an important tool for the management of ground-level ozone
      pollution. This paper has two broad aims: it illustrates the potential of a
      geographic information system (GIS) for enhancing an existing spatially
      aggregated, anthropogenic emissions inventory (EI) for Tucson, AZ, and it
      discusses the ozone-specific management implications of the resulting spatially
      disaggregated EI. The main GIS-related methods include calculating emissions for
      specific features, spatially disaggregating region-wide emissions totals for area
      sources, and adding emissions from various point sources. In addition, temporal
      allocation factors enable the addition of a multi-temporal component to the
      inventory. The resulting inventory reveals that on-road motor vehicles account
      for approximately 50% of VOC and NOx emissions annually. On-road motor vehicles
      and residential wood combustion are the largest VOC sources in the summer and
      winter months, respectively. On-road motor vehicles are always the largest NOx
      sources. The most noticeable weekday vs. weekend VOC emissions differences are
      triggered by increased residential wood combustion and increased lawn and garden
      equipment use on weekends. Concerning the EI's uncertainties and errors, on-road
      mobile, construction equipment, and lawn and garden equipment are identified as
      sources in the most need of further investigation. Overall, the EIs spatial
      component increases its utility as a management tool, which might involve
      visualization-driven analyses and air quality modeling.

PMID- 11826725
TI  - Effectiveness of arm supports during typing for adults with neurological
      disorders.
AB  - Four computer-typing accommodations were evaluated to determine if arm supports
      would enhance typing performance and/or comfort of adults with neurological
      disorders. Each of 12 adults (6 females and 6 males) participated in 7-min typing
      tasks under the following conditions: 1) without arm support, 2) Ergo Rest arm
      support, 3) custom arm support in fixed mode, and 4) custom arm support with
      movable mode. The objective dependent variables were speed, errors, and type of
      errors. The subjective dependent measures were reported body part discomfort, and
      arm support ratings. The data were found to be nonparametric in nature.
      Therefore, nonparametric techniques were employed to analyze the data. Only one
      of the objective dependent measures were statistically significant; Type of error
      (additional key). This result may be attributed to the wide range of disability
      manifestations among participants. Subjective dependent measures were found to be
      statistically significant, leading to the conclusion that typing with an arm
      support was more comfortable and easier than without an arm support.

PMID- 11826726
TI  - Work-related musculoskeletal disorders: design as a prevention strategy. A
      review.
AB  - Work-related musculoskeletal disorders are of serious concern to many
      organizations, including industry, insurance, and health care. They are also of
      immediate concern to the workers and their families who are adversely affected by
      these disorders. Work-related musculoskeletal disorders are a substantial source
      of economic drain to these organizations. Sources of this drain include economic
      losses incurred from lost or decreased productivity as well as medical treatment
      and indemnity costs. Therefore, it is within the best interest of these
      organizations to prevent work-related musculoskeletal disorders from occurring,
      before they manifest into serious issues of medical, social, and economic
      concern. The purpose of this paper is to review the concept of work-related
      musculoskeletal disorders and discuss the basis of their prevention as a primary
      means of occupational injury and illness management. The principal contributory
      role of ergonomics/human factors is presented as a viable means of prevention and
      an important contributor to the comprehensive management of these disorders.

PMID- 11826727
TI  - Precision grip force control of older and younger adults, revisited.
AB  - This study revisited the hypothesis that older adults lose some ability to
      efficiently control precision grip force. A previous study demonstrated such a
      decrement in older adults' performance in a vertical lift and support maneuver.
      This study employed a similar paradigm in which dynamic forces were applied with
      a simulated hand tool while measuring grip force and force applied with the tool.
      Measures of grip force control reflected subjects' modulation of grip force in
      parallel with force transmitted with the tool and their scaling of the ratio of
      grip to applied force. Nine older (> 65 years) and 9 younger (< 65 years)
      subjects' grip force control measures were compared with emphasis on recruiting
      active older individuals for whom upper extremity usage was high in their daily
      life. No statistically significant age effects were found in either force control
      measure, suggesting a smaller age-related decrement than reported in a previous
      study.

PMID- 11826728
TI  - Performance reduction in finger amputees when reaching and operating common
      control devices: a pilot experimental investigation using a simulated finger
      disability.
AB  - This paper reports results of an experimental laboratory investigation to
      determine if finger amputations (most pervasive upper extremity injury in the
      United States) result in significant work performance deterioration in tasks
      requiring operation of common control devices found in industrial settings. Ten
      male student volunteers from the University of Cincinnati participated in this
      study. The finger disability simulated was of an extreme nature, and was defined
      as the loss of four fingers in the preferred hand and the thumb in the
      nonpreferred hand. While being seated, participants activated 5 types of
      industrial control devices (a rotary dial, a push button, a toggle switch, a
      castor wheel, and a rocker switch). The controls were assembled on a device
      attached to a cylindrical pole, such that the control assembly could move up and
      down the cylindrical pole. The vertical height of control location (15, 20, and
      30 in. from the seat reference point) and angle of control location in vertical
      plane (0 degree, 45 degrees, 90 degrees, and 135 degrees) were varied in the
      experiment. Participants also had their torso restrained or unrestrained while
      reaching and activating controls, in addition to the presence or absence of the
      simulated disability in each participant. Functional reaches and arm reaches from
      the wall were measured for participants in the sample to determine the distances
      at which to place the control pole assembly. If a participant was able to reach
      the control, the time taken to activate and operate the control was recorded.
      Overall results indicate that participants took significantly longer (p < 0.05)
      to activate controls in the presence of the simulated disability. Physical
      restraint did not significantly alter performance provided the participant was
      able to reach the control. The type of control and the height of location of the
      control also significantly affected work performance.

PMID- 11826729
TI  - Training to reduce postural sway and increase functional reach in the elderly.
AB  - Poor balance is one of the most common risk factors for falling, a common cause
      of work-related injury and death. To evaluate the effects of a 10-week
      intervention program on balance in older adults, 12 participants aged 61-77 years
      (age = 70.4 +/- 5.4 years; mean +/- SD) completed an exercise program (60 min, 2
      days.week-1 for 10 weeks) performed while laying/sitting on large air-filled
      exercise balls (Thera-Band). Several postural sway composite scores (determined
      while standing with feet apart and semitandem, eyes open and closed) improved (p
      < or = 0.05) including medial-lateral amplitude and speed of sway (reduced by
      approximately 9%), and instantaneous speed (reduced by approximately 13%).
      Reductions in XY area approached (p = 0.06) statistical significance and anterior
      posterior amplitude and speed of sway did not change. Functional reach also
      improved (20.3%). These results suggest that challenging the physiological
      systems involved in balance control while on the nonstable support surface of the
      exercise balls improves both static and dynamic balance in older adults and may
      reduce the risk for falling.

PMID- 11826730
TI  - Workplace disability management in postpolio syndrome.
AB  - Postpolio syndrome (PPS) is generally defined as a clinical syndrome of new
      weakness, fatigue, and pain in individuals who have previously recovered from
      acute paralytic poliomyelitis. These new problems may lead to loss of employment
      as well as new deficits in instrumental activities in daily living (cleaning,
      washing, shopping, transportation, etc.), walking, climbing stairs, and personal
      assistance. We presented three cases of PPS with working disabilities in Japan,
      and stated the issues confronted with. Particularly at the workplace, PPS
      individuals need special supports from both rehabilitation medicine and
      occupational health services, including improved nutrition, achieving ideal body
      weight, regular and sensible exercise, frequent checkups, and modifying working
      conditions.

PMID- 11826732
TI  - Prevention concept in industry: improvement in occupational safety and health
      protection--an empirical study.
AB  - This prevention concept offers a contribution to the expansion of the set of
      instruments for occupational safety and health protection within workplace
      prevention. The concept involves the multilateral analysis of work conditions.
      The utilized instruments include a strategy group, a survey, a health issue round
      table, and an analysis of work demands, and lead to synergy effects at the
      results level. Employees are drawn into the analysis of work conditions and
      workplace design solutions for the improvement of the work situation. The
      prevention concept was tested in a large company and its application established
      in practice. It was accepted by all participants, and the comparison with the
      previous situation (defined only through the analysis of work demands)
      demonstrated a significant improvement in health protection.

PMID- 11826731
TI  - Physical ergonomics in low-back pain prevention.
AB  - This paper reviews the current state of knowledge regarding the tools used in
      evaluating the workplace and worker in hopes of preventing low-back injury.
      Information regarding the current state of expenditure and trends toward
      ergonomic intervention are discussed. Acknowledgment is made of the increasing
      shift of responsibility from Compensation Boards to industry, and a review
      proactive preventative strategies and medical knowledge is included. Current
      ergonomic assessment tools are reviewed and the role of the Physical Ergonomist
      is introduced. Suggestions are made regarding the value of current and future
      approaches in prevention and direction of research.

PMID- 11826733
TI  - [Progress in molecular biology and pathophysiology of pain manifestation. New
      aspects for pain therapy in rheumatology].

PMID- 11826734
TI  - Nociception, pain, and antinociception: current concepts.
AB  - The physiology of nociception involves a complex interaction of peripheral and
      central nervous system (CNS) structures, extending from the skin, the viscera and
      the musculoskeletal tissues to the cerebral cortex. The pathophysiology of
      chronic pain shows alterations of normal physiological pathways, giving rise to
      hyperalgesia or allodynia. After integration in the spinal cord, nociceptive
      information is transferred to thalamic structures before it reaches the
      somatosensory cortex. Each of these levels of the CNS contain modulatory
      mechanisms. The two most important systems in modulating nociception and
      antinociception, the N-methyl-D-aspartate (NMDA) and opioid receptor system, show
      a close distribution pattern in nearly all CNS regions, and activation of NMDA
      receptors has been found to contribute to the hyperalgesia associated with nerve
      injury or inflammation. Apart from substance P (SP), the major facilitatory
      effect in nociception is exerted by glutamate as the natural activator of NMDA
      receptors. Stimulation of ionotropic NMDA receptors causes intraneuronal
      elevation of Ca2+ which stimulates nitric oxide synthase (NOS) and the production
      of nitric oxide (NO). NO as a gaseous molecule diffuses out from the neuron and
      by action on guanylyl cyclase, NO stimulates in neighboring neurons the formation
      of cGMP. Depending on the expression of cGMP-controlled ion channels in target
      neurons, NO may act excitatory or inhibitory. NO has been implicated in the
      development of hyperexcitability, resulting in hyperalgesia or allodynia, by
      increasing nociceptive transmitters at their central terminals. Among the three
      subtypes of opioid receptors, mu- and delta-receptors either inhibit or
      potentiate NMDA receptor-mediated events, while kappa opioids antagonize NMDA
      receptor-mediated activity. Recently, CRH has been found to act at all levels of
      the neuraxis to produce analgesia. Modulation of nociception occurs at all levels
      of the neuraxis, thus, eliciting the multidimensional experience of pain
      involving sensory-discriminative, affective-motivational, cognitive and locomotor
      components.

PMID- 11826735
TI  - Peripheral analgesic and antiinflammatory effects of opioids.
AB  - Traditionally, opioids were considered the prototype of centrally acting
      analgesics. In the past decade a substantial literature has emerged demonstrating
      that opioids can produce potent and clinically measurable analgesia by activation
      of opioid receptors on peripheral terminals of primary sensory neurons. In
      addition, endogenous ligands of these peripheral receptors were discovered in
      immune cells. Major recent findings in peripheral opioid analgesia include the
      relative lack of tolerance under inflammatory conditions, tetrapeptides as novel
      peripherally restricted compounds, the potent antiinflammatory activity of mu-
      and kappa-agonists and the identification of selectins as important molecules
      governing the homing of opioid cells to injured tissue. In addition to the
      extensively documented efficacy of locally applied morphine in post-surgical
      pain, clinical studies have now moved into the field of chronic arthritic pain.

PMID- 11826736
TI  - ["Applications of new therapies in rheumatology practice and management--evidence
      based rheumatology on this side of and beyond randomized studies" Workshop 6th
      and 7th April 2001 Weimar].

PMID- 11826737
TI  - [Expectations of patients with rheumatism from new therapies].
AB  - The expectation of patients with rheumatism concerning newly developed therapies
      are described on the basis of the experience of the patients' self-help movement.
      Most important are the wishes of the patients for healing and for treatment which
      is safe and without adverse effects. The measures necessary for better
      implementation of research results in the treatment of patients are described.

PMID- 11826738
TI  - [Applied evidence-based medicine].
AB  - The success of evidence-based medicine (EbM) will also depend whether its
      effectiveness is proven in empirical studies. The main question is how the
      information-seeking behaviour of physicians can be modified. A series of studies
      have shown that their information management is frequently not based on a
      rational model of knowledge acquisition. In particular, many studies concerning
      the implementation of guidelines as a practical application of EbM have
      demonstrated that, in addition to a general skepticism about guidelines, many
      practical obstacles are relevant. An optimal implementation strategy should
      consider these from the beginning.

PMID- 11826739
TI  - [Therapy with not yet approved drugs or for not yet approved indications].

PMID- 11826740
TI  - [Evidence-based medicine and applying new therapies in general practice: wish and
      reality].
AB  - In the last years some important therapies were introduced in the treatment of
      rheumatoid arthritis (RA), which represent a significant clinical advance. This
      concerns the introduction of TNF blockade with etanercept and inflixmab, the
      combination of DMARDs, leflunomide and the COX-2-specific inhibitors. In the year
      2000 the restrictive social law in Germany, the collective and individual budgets
      for medicaments, did prevent a broader use of the very expensive therapy with TNF
      blockade. A rising number of international healthcare studies shows a profound
      potential for saving costs by improving the functional capacity (HAQ) in patients
      with RA. The biologicals and leflunomide have this potential. To realise the
      potential of reducing healthcare costs by an optimal therapy of RA some
      modification of the restrictive social law is necessary as well as the
      introduction of disease-management programs.

PMID- 11826741
TI  - [Current status of therapeutic approaches in spondyloarthropathies].
AB  - Anti-TNF therapy seems to be highly effective in AS. Based on the available
      results, this treatment seems to be at least as effective as in RA. Furthermore,
      because no other treatments are available for AS--in contrast to RA or psoriatic
      arthritis--infliximab might even become a first-line immuno-suppressive treatment
      in patients with severe, active AS. A dosage of 5 mg/kg seems to be required and
      intervals between 6-12 weeks seem to be necessary depending on the disease
      activity. It remains to be shown what the long-term effects are, whether the
      patients benefit from long-term therapy and whether radiological progression and
      ankylosis can be stopped. Allergy, lupus-like diseases and tuberculosis are rare
      side effects which need to be addressed. At first glance, the possible benefits
      of anti-TNF therapy seem to outweigh these shortcomings.

PMID- 11826742
TI  - [Evidence-based therapy of systemic sclerosis].
AB  - For the treatment of different forms of systemic sclerosis (SSc), drugs play a
      predominant role. Depending on disease activity as well as type and severity of
      cutaneous, vascular and internal organ manifestations, different systemic
      (antiinflammatory, immunosuppressive, antifibrotic) or organ-specific therapies
      are used. The scientific basis of most treatment modalities is insufficient and
      incomplete. There is sufficient evidence for an antiinflammatory and
      antiproliferative efficacy of glucocorticosteroids, methotrexate,
      cyclophosphamide and cyclosporine A in the treatment of diffuse cutaneous
      systemic sclerosis. Vasoactive therapies play an important role in treating
      Raynaud's phenomenon (nifedipine or other dihydropyridines, prostaglandin
      analogs, losartan, prazosine), and arterial (ACE blockers, AT-1 antagonists) or
      pulmonary (epoprostenol) hypertension. Cyclophosphamide is effective in fibrosing
      alveolitis, prokinetic substances (metoclopramid, domperidone) in
      gastroesophageal dysmotility or octreotide in intestinal pseudoobstruction.
      Physical therapies (e.g., massage) are poorly studied. In particular cases,
      surgical measures (e.g., removal of calcifications) are necessary.

PMID- 11826743
TI  - [National database documentation for collecting, controlling and quality
      assurance of new therapies in rheumatoid arthritis].
AB  - The national database of the German Collaborative Arthritis Centres is well
      established in German rheumatology as a tool for the observation and assessment
      of treatments. The usage and spread of new drugs and treatment principles is
      regularly observed. Discussion about practice variations in treatment contributes
      to the internal quality assessment in the participating arthritis centres.

PMID- 11826744
TI  - [New basic therapeutic drugs from the viewpoint of evidence-based therapy].
AB  - Leflunomide, infliximab and etanercept belong to a new generation of disease
      modifying antirheumatic drugs: they achieve a sustained improvement of clinical
      as well as biochemical parameters of the disease activity. Consecutively, indices
      of life quality become better and they are essentially able to prevent structural
      joint damage. The therapeutic rating of these new agents in early and advanced RA
      compared to the commonly used DMARDs and combination therapies has to be
      evaluated in further trials. Controlled studies are the basis of evidence-based
      therapy. But also the daily clinical experience as well as costs of therapy may
      have an impact on decision making. The focus of antirheumatic therapy should be
      on the achievement of an early and sustained remission in RA patients.

PMID- 11826745
TI  - [Combined basic therapeutic drugs. From individual hope to targeted use].
AB  - Accumulating evidence suggests that treatment of rheumatoid arthritis (RA) with
      two or more disease-modifying antirheumatic drugs (DMARDs) is more efficient than
      single agent therapy. Randomized clinical trials demonstrated the efficacy of
      various combinations such as methotrexate plus sulfasalazine plus
      hydroxychloroquine, methotrexate plus ciclosporine or methotrexate plus
      infliximab, respectively. In contrast to these data, however, most German
      rheumatologists use combination therapy in a small percentage of patients with
      active RA. Thus, consensus criteria should be defined when and how to use
      combination therapy in the treatment of active disease. We suggest that
      combination therapy should be started if active disease is still present after
      three months of treatment with a single standard DMARD, mostly methotrexate, plus
      low dose prednisolone and that combination DMARD therapy should be used before
      TNF blocking agents.

PMID- 11826746
TI  - [Current status of COX II inhibitors in therapy of rheumatoid arthritis in
      comparison with conventional non-steroidal anti-inflammatory agents. Attempt at
      an evaluation with regard to evidence-based medicine].

PMID- 11826747
TI  - [Use of glucocorticoids in rheumatoid arthritis. Inhibition of disease
      progression versus risk of steroid osteoporosis].
AB  - This is a short overview of low dose oral treatment with 5-7.5 mg
      prednisolone/day in RA with emphasis on radiographic progression. Short-term
      studies over 1-2 weeks with 7.5-15 mg prednisolone/day demonstrate advantage over
      placebo and--less so--over NSAID in improving RA symptoms; over 6-12 months
      prednisolone seems to be less superior. Older studies were unable to demonstrate
      an inhibition of progression seen on radiographs. In the Kirwan study, there was
      a significant inhibition of x-ray progression with 7.5 mg prednisolone/day versus
      placebo. The German low-dose prednisolone treatment (LDPT) study demonstrated a
      significant retardation of radiographic progression with only 5 mg
      prednisolone/day in addition to DMARD treatment with parenteral gold or
      methotrexate versus DMARD + placebo in early RA during the first year of
      treatment while there was no difference between both groups during the second
      year. These data are in favor of a "bridging" treatment with low dose
      prednisolone. The risks of corticosteroid treatment are discussed, including an
      increased mortality rate as an independent risk factor. Two randomized studies
      and a metaanalysis indicate the development of steroid osteoporosis in RA already
      with low doses. As with every treatment, benefit and risk have to be considered
      carefully.

PMID- 11826748
TI  - [IV: Small group workshop for developing future measures and projects. Evidence
      based therapy in rheumatology with special reference to applications of new drugs
      -formulation of possible goals and possibilities for meeting them. Rheumatoid
      arthritis ].

PMID- 11826749
TI  - [IV: Small group workshop for developing future measures and projects. Evidence
      based therapy in rheumatology with special reference to applications of new drugs
      -formulation of possible goals and possibilities for meeting them. Osteoporosis
      in rheumatic diseases].
AB  - Secondary osteoporosis is a common, late complication of inflammatory rheumatic
      diseases. Despite its great socio-economic implications for the individual, there
      is still a lack of appreciation of this problem. This may result in an inadequate
      or insufficient prophylaxis and therapy. The participants of this discussion
      group, therefore, approve of further investigations in this field to gather new
      relevant data, e.g., for our core documentation on rheumatic diseases. Of special
      importance is the registration of long-term patients obtaining documented,
      individual long-term therapy (e.g., cortisone). As well as epidemiologic and
      clinical research projects, it is imperative to do basic research into the
      pathogenesis of secondary osteoporosis and find new therapeutic approaches for
      curing rheumatic disease.

PMID- 11826750
TI  - [Presentation of the Erlangen Competence Center].

PMID- 11826751
TI  - [Young and unencumbered--Adolf Strumpell (1853-1925)].

PMID- 11826752
TI  - [Fractures of the ankylosed spine in ankylosing spondylitis].

PMID- 11826753
TI  - Regulation of signal transduction by the Fc gamma receptor family members and
      their involvement in autoimmunity.
AB  - Recent studies on the nature and mode of action of inhibitory receptors and their
      intracellular phosphatase effector enzymes have identified a new area of research
      in the etiology of autoimmune diseases. Myeloid cells play a critical role in
      autoimmunity through their IgG receptors. A number of recent findings reveal that
      such cells express inhibitory receptors, including the elusive CD32/Fc gamma RIIB
      isoform, and express inhibitory phosphatases like SHP-1 and SHIP. Animals lacking
      the effector phosphatases exhibit a pronounced autoimmune and/or pro-inflammatory
      phenotype. Animals deficient in the expression of the inhibitory receptors often
      display a much less severe phenotype, likely due to the fact that hematopoietic
      cells have numerous and probably redundant inhibitory receptors. Genetic
      deficiencies in the limited number of effector molecules (SHP-1 and SHIP) lead to
      more dramatic effects on hematopoietic cells and level of inflammation in such
      animals. These recent findings in animal models open the intriguing possibility
      that the human homologues of genes encoding the inhibitory receptors like Fc
      gamma RIIB or effector phosphatases like SHIP might contribute to autoimmune
      diseases. However, while identification of genes involved in autoimmunity will
      greatly aid in diagnosis of human autoimmune disease, it is necessary to
      understand the biochemical mechanisms of action of the numerous inhibitory
      receptors and phosphatases in the hematopoietic system. Such information will
      permit the rational design of more efficient and effective treatments for
      patients. Additional experiments directed at the role and mechanism(s) of action
      of the inhibitory phosphatases SHP-1 and SHIP will uncover new candidates for
      diagnosis and treatment of autoimmune diseases.

PMID- 11826754
TI  - Role of the B7-CD28/CTLA-4 pathway in autoimmune disease.

PMID- 11826755
TI  - Abnormal T lymphocyte signal transduction in systemic lupus erythematosus.

PMID- 11826756
TI  - Lyn/CD22/SHP-1 and their importance in autoimmunity.

PMID- 11826757
TI  - Regulation of immune responses by E3 ubiquitin-protein ligases.

PMID- 11826758
TI  - Keeping the T-cell immune response in balance: role of protein tyrosine
      phosphatases in autoimmunity.

PMID- 11826759
TI  - The role of TNF/TNFR in organ-specific and systemic autoimmunity: implications
      for the design of optimized 'anti-TNF' therapies.

PMID- 11826760
TI  - CD40 signaling and autoimmunity.

PMID- 11826761
TI  - TGF-beta: receptors, signaling pathways and autoimmunity.

PMID- 11826762
TI  - Interleukin-2 signaling and the maintenance of self-tolerance.
AB  - IL-2 plays an important and complex role in the immune system, serving as a
      growth factor, a differentiation factor, and a regulator of cell death. It shares
      many of these functions with other cytokines such as IL-15, which complicates the
      interpretation of the IL-2-deficient phenotype. Nonetheless, it is clear that a
      major indispensable role of IL-2 signaling, at least in mice, is to limit the
      number of activated T cells in the periphery after exposure to self- or
      environmental antigens. Although we still do not understand the mechanism by
      which this occurs, there emerge several general conclusions that provide a
      foundation for future work on this issue. The autoimmune phenotype associated
      with IL-2 deficiency results from the dysregulated activity of thymus-derived TCR
      alpha beta CD4+ and/or CD8+ T cells. The process requires an initial antigenic
      stimulus (e.g., from intestinal flora or self-antigens), but can then spread to
      naive bystander T cells by an undefined mechanism. A key observation is that
      neighboring T cells with intact IL-2 signaling can suppress the dysregulated
      activity of IL-2- or IL-2R-deficient T cells in a dominant manner, indicating
      that IL-2-based immune regulation is a systemic rather than cell autonomous
      property. The IL-2R signal responsible for maintaining homeostasis is not
      dependent on either the Shc or Stat5 pathways, therefore AICD, which is Stat5
      dependent in vitro, cannot be the critical mechanism. Finally, expression of the
      IL-2R in the thymus and not the periphery appears sufficient to suppress the
      autoimmune phenotype, suggesting that IL-2 signaling may be required for some
      aspect of thymocyte selection and/or differentiation that has so far gone
      undetected. These observations can be combined into a unified model wherein IL-2
      signaling is required for the development of a regulatory T-cell subset that
      serves to terminate antigen-induced responses of TCR alpha beta T cells. On the
      other hand, the role of IL-2 in the maintenance of self-tolerance could be
      multifaceted, with no single model accounting for all experimental findings. Of
      note, most of our knowledge regarding IL-2 signaling and tolerance has come from
      studies of knockout mice. Conceptually, it is important to remember that the
      function of a molecule such as IL-2 is not simply the inverse of the phenotype
      seen when that molecule is absent, since necessity and sufficiency are not always
      coupled in physiological processes. In this regard, perhaps new insights into
      this important issue can be gained by better defining when and where IL-2
      signaling normally occurs in wild-type animals and the functional status of the T
      cells involved.

PMID- 11826763
TI  - Recombinant follicle-stimulating hormone stimulates ovarian androgen synthesis in
      down-regulated ovulatory women.
AB  - In order to study androgen secretion during controlled ovarian hyperstimulation
      for in-vitro fertilization-embryo transfer, an open randomized study comparing
      the response to recombinant or urinary follicle-stimulating hormone (FSH) in down
      regulated cycles was performed. During FSH administration significant increases
      in testosterone, androstenedione and dehydroepiandrosterone sulfate (DHEAS)
      levels were observed. During the same period a slight decrease in luteinizing
      hormone (LH) levels was seen. At all times during the stimulation period a
      significant correlation between estradiol and testosterone or androstenedione
      levels was observed. We conclude that FSH, through granulosa derived paracrine
      factors, initiates thecal androgen synthesis and secretion.

PMID- 11826764
TI  - Concentrations of insulin-like growth factor (IGF)-I and IGF binding protein-3 in
      the follicular fluid of women undergoing ovarian hyperstimulation with different
      gonadotropin preparations.
AB  - Insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) have an
      important regulatory role in follicular development and oocyte maturation. The
      aim of this prospective, randomized, double-blind study was to measure the
      concentrations of IGF-I and IGFBP-3 in follicular fluids collected from infertile
      women undergoing ovarian hyperstimulation using three different gonadotropin
      preparations. Twenty infertile women (mean age 33 years, range 28-40) undergoing
      in vitro fertilization (IVF) programs were recruited. After a written informed
      consent, each woman randomly underwent a long-protocol for ovarian
      hyperstimulation using gonadotropin-releasing hormone (GnRH)-analog and one of
      the following recombinant- and urinary-gonadotropins--alpha-follitropin, beta
      follitropin or urofollitropin. Serum 17 beta-estradiol (E2) levels and follicle
      growth were assessed during the follicular phase. The concentrations of IGF-I and
      IGFBP-3 in the follicular fluid of aspirated dominant follicles were measured
      directly. Women treated with alpha-follitropin needed significantly lower doses
      of follicle-stimulating hormone (FSH) compared to those receiving beta
      follitropin (p < 0.05). No other statistically significant differences were
      detected between groups. Serum E2 levels increased in the three groups from early
      to late follicular phase. Follicular fluid IGF-I and IGFBP-3 concentrations did
      not differ significantly in the three groups of women. A statistically
      significant relationship was observed between follicular fluid IGF-I and IGFBP-3
      levels (r = 0.41, p = 0.001). Oocyte maturation correlated in a positive manner
      with IGF-I (r = 0.34, p = 0.01) and IGFBP-3 (r = 0.29, p = 0.03). These findings
      show that both recombinant- and urinary-gonadotropin preparations were equally
      effective in releasing IGF-I and IGFBP-3 in the follicular fluid of dominant
      follicles, and confirmed the role of these compounds on oocyte maturation.

PMID- 11826765
TI  - Ovulation induction with pulsatile gonadotropin-releasing hormone (GnRH) or
      gonadotropins in a case of hypothalamic amenorrhea and diabetes insipidus.
AB  - Hypothalamic amenorrhea is a treatable cause of infertility. Our patient was
      presented with secondary amenorrhea and diabetes insipidus. Cortisol and
      prolactin responded normally to a combined insulin tolerance test (ITT) and
      thyrotropin-releasing hormone (TRH) challenge, while thyroid-stimulating hormone
      (TSH) response to TRH was diminished, and no response of growth hormone to ITT
      was detected. Both luteinizing hormone (LH) and follicle-stimulating hormone
      (FSH) levels increased following gonadotropin-releasing hormone (GnRH) challenge.
      No response of LH to clomiphene citrate challenge was detected. Magnetic
      resonance imaging findings demonstrated a midline mass occupying the inferior
      hypothalamus, with posterior lobe not visible and thickened pituitary stalk.
      Ovulation induction was carried out first with combined human menopausal
      gonadotropins (hMG/LH/FSH) (150 IU/day) and afterwards with pulsatile GnRH (150
      ng/kg/pulse). Ovulation was achieved with both pulsatile GnRH and combine
      gonadotropin therapy. Slightly better results were achieved with the pulsatile
      GnRH treatment.

PMID- 11826766
TI  - Messenger ribonucleic acid for the mouse decidual prolactin is present and
      induced during in vitro decidualization of endometrial stromal cells.
AB  - Although decidualization of endometrial stromal cells is crucial for blastocyst
      implantation and maintenance of pregnancy, its complex mechanism still remains
      largely unknown. To explore the mechanisms of decidualization, we have
      established an in vitro decidualization model in mice. Through extraction of mRNA
      from endometrial stromal cells for subsequent reverse transcriptase polymerase
      chain reaction analysis, we found that two ovarian hormones, 17 beta-estradiol
      and progesterone, induced morphological changes and expression of mRNA for
      prolactin (PRL) and the decidual/trophoblastic PRL-related protein (d/tPRP) in
      cultured mouse endometrial stromal cells. The expression of mRNA for the decidual
      PRL was also detected in the mouse decidua in vitro. In conclusion, mouse mRNA
      for decidual PRL is present and induced by estradiol and progesterone through in
      vitro decidualization of endometrial stromal cells.

PMID- 11826767
TI  - The effect of 17 beta-estradiol on weight, blood glucose and plasma insulin
      levels in diabetic rats.
AB  - Steroid hormones are used to treat a variety of diseases in both diabetic and non
      diabetic people. Since steroid hormones affect glucose metabolism, the aim of
      this study was to examine whether 3.3 mg/kg body weight of orally administered 17
      beta-estradiol (E2) would adversely affect the body weight, blood glucose and
      plasma insulin levels of streptozotocin (STZ)-induced diabetic rats. Diabetes was
      induced by a single dose of STZ given intraperitoneally (60 mg/kg body weight).
      Administration of E2 caused a decrease in the weight of diabetic rats compared to
      untreated diabetic rats two weeks after the experiment. Although the blood
      glucose level in the E2-treated rats was numerically lower than that of untreated
      diabetics, the difference was not statistically significant. The plasma insulin
      level in E2-treated diabetic rats (0.44 +/- 0.1 ng/ml) was not significantly
      different from that of untreated diabetic rats (0.52 +/- 0.1 ng/ml). The plasma
      insulin levels of E2-treated and untreated diabetic rats were, however,
      significantly (p < 0.05) lower than that of normal rats (1.18 +/- 0.5 ng/ml). In
      conclusion, E2 caused progressive loss of body weight, but did not significantly
      alter the blood glucose and plasma insulin levels of diabetic rats when compared
      to normal controls. This shows that E2 may be given to diabetic patients without
      significantly disrupting glucose homeostasis.

PMID- 11826768
TI  - Pheochromocytoma in a pregnant woman with multiple endocrine neoplasia type 2a.
AB  - Pheochromocytoma is a rare cause of hypertension. Its coexistence with pregnancy
      is exceptional and laparoscopic removal has rarely been reported. We describe the
      case of a 34-year-old woman with multiple endocrine neoplasia type 2a (MEN 2a)
      with adrenal pheochromocytoma diagnosed in the 6th week of pregnancy. After
      pretreatment with phenoxybenzamine, a successful transperitoneal laparoscopic
      adrenalectomy was performed in the twentieth week of gestation. The management of
      pheochromocytoma in pregnancy and the indications for laparoscopic surgery in
      pregnant patients are discussed.

PMID- 11826769
TI  - Different expression of estrogen receptors alpha and beta in human myometrium and
      leiomyoma during the proliferative phase of the menstrual cycle and after GnRHa
      treatment.
AB  - Uterine leiomyomas (uterine fibroids) are sex-steroid dependent benign tumors.
      Limited knowledge is available regarding the role of estrogen and their receptors
      in the regulation of fibroids in premenopausal women, and in their shrinkage
      after treatment with a gonadotropin-releasing hormone analogue (GnRHa). The
      expression of the two subtypes of the estrogen receptor (ER), ER alpha and ER
      beta, was studied in leiomyoma and homologous myometrium from women in the
      proliferative phase of the menstrual cycle and from women treated with GnRHa. The
      mRNA levels of ER alpha and ER beta were monitored by solution hybridization and
      in situ hybridization, and receptor proteins were detected and localized by
      immunohistochemistry. Both ER alpha and ER beta were present in the leiomyomas
      and homologous myometrium. The ER alpha mRNA level in the leiomyomas was higher
      than in the surrounding myometrium. The ER beta mRNA level was lower than that of
      ER alpha in both groups. ER beta immunoreactivity was lower in leiomyomas when
      compared with the myometrium after GnRHa treatment, while ER alpha was higher in
      the leiomyomas. The present results imply that the increased ratio of ER alpha/ER
      beta observed in the fibroids after GnRHa treatment could reflect or be the cause
      of the shrinkage of the leiomyoma, which is the clinical outcome of this
      treatment.

PMID- 11826770
TI  - Hormone replacement therapy and cancer.
AB  - Sex steroids are not known to damage DNA directly. They can stimulate or inhibit
      cell proliferation, and thus can modulate tumor developmental progression. Sex
      steroid-related tumors in women are represented by breast cancer and endometrial
      cancer, and a possible relationship exists between sex steroids and both ovarian
      and colon cancer. Among current ERT users or those who stopped use 1-4 years
      previously, the relative risk of having breast cancer diagnosed increases by a
      factor of 1.023 for each year of hormone use. This increase is comparable with
      the effect on breast cancer of delaying menopause, and seems to be largely
      limited to lean women. The breast cancers diagnosed during ERT are more likely to
      contain ER and are less aggressive. Some reports indicate no increase in breast
      cancer mortality in HRT users. Recent data suggest that an estrogen-progestin
      regimen may increase breast cancer risk beyond that associated with estrogen
      alone. However, the effect of progestogens on the breast awaits further
      clarification. ERT/HRT is generally considered to be contraindicated in breast
      cancer patients, as no firm data are yet available from randomized clinical
      trials. Despite the potential risks, ERT/HRT could be considered for breast
      cancer patients suffering from menopausal symptoms resistant to alternative
      treatments, after completely informed consent is given, particularly in women
      with ER-(hormone-resistant) cancers. Unopposed estrogen therapy is known to
      increase endometrial cancer risk, and is appropriate only for hysterectomized
      women. To negate the excess risk of endometrial hyperstimulation, an adequate
      progestin dose must be given in a continuous combined regimen or for an
      appropriate number of days in sequential regimens (10 days or more for some
      progestogens or 12 days or more for other progestogens). An appropriate
      combination of estrogen and progestin does not appear to increase, and may even
      decrease, the risk of endometrial cancer. HRT is generally considered to be
      contraindicated in endometrial cancer patients. Despite the potential risks, HRT
      could be considered for patients suffering from menopausal symptoms resistant to
      alternative treatments, after completely informed consent is given. Available
      data suggest a reduced risk of colorectal adenoma and colon cancer in current
      users of HRT, but definitive studies are still needed. There is no
      contraindication to HRT prescription in colon cancer survivors. Consistent
      epidemiological data describe a decreased incidence of ovarian cancer with oral
      contraceptive use during the reproductive years. Studies on HRT and risk of
      epithelial ovarian cancer have produced conflicting results but most data seem to
      exclude a strong association. While no data contraindicate HRT use in epithelial
      ovarian cancer survivors, current studies do not allow us to exclude the
      possibility that estrogens alone could stimulate ovarian cancer growth in a small
      fraction of patients. Additional studies are required. It is important to
      consider that not all estrogens and progestins are used with the same dosage,
      route of administration (oral, transdermal and for estradiol intranasal) and,
      mostly, different estrogens do not show the same bioavailability and tissue
      effects. The available data do not allow to discriminate for all these variables
      and therefore it is inappropriate to consider jointly all forms of hormonal
      therapy. This issue is considered as an important area for future evaluation and
      research. The International Menopause Society is in the process of drawing up
      specific recommendations for further research in the field of HRT and cancer.

PMID- 11826771
TI  - Comparison of biochemical markers of bone turnover and bone mineral density in
      different groups of climacteric women.
AB  - In the present study we evaluated plasma levels of two markers of bone turnover
      (osteocalcin (OC) and urinary pyridinium cross-links) in association with bone
      mineral density (BMI) in different groups of climacteric women. We have
      investigated 158 women in pre-, peri- and postmenopause. Blood and urine samples
      for assay of hormones and markers were collected and bone mineral density (BMD)
      was measured by DEXA densitometry in the distal tenth of the non-dominant
      forearm. There was a significant increase in mean absolute levels of both markers
      in perimenopause and women in natural and surgical menopause, with respect to
      women in premenopause. There was a significant correlation between OC and
      deoxypyridoline (DPYR) in peri- and postmenopause groups. In peri- and
      postmenopause groups, BMD was correlated with an increase in the biochemical
      markers of bone remodeling. In the present study, OC and DPYR were found to have
      good sensitivity for identifying perimenopausal women with pathological BMD. The
      present results reveal a positive and significant correlation between DPYR and
      OC, inversely proportional to BMD, during hormone replacement therapy. These
      markers therefore turn out to be sensitive not only for monitoring severe
      pathology of bone turnover, but also for monitoring slight physiological deficits
      in bone equilibrium beginning in perimenopause.

PMID- 11826772
TI  - Hormones, cytokines and fetal anomalies in habitual abortion.
AB  - Recurrent miscarriage may be due to an inherently abnormal embryo (e.g.
      chromosomal aberrations), or maternal factors (e.g. uterine anomalies or
      antiphospholipid antibodies). However, there may be another mechanism; fetuses
      may have anomalies induced by toxic maternal factors. Early ultrasound scanning
      has revealed structural anomalies in karyotypically normal embryos in pregnancies
      that have terminated in first-trimester missed abortion. The serum of recurrently
      miscarrying women is toxic to blastocysts, embryos and fetuses. Teratogens such
      as cyclophosphamide or toxins such as lipopolysaccharide cause fetal demise by
      excessive apoptosis. Excessive apoptosis may be mediated by tumor necrosis factor
      alpha and other cytokines. Both immunomodulation and hormonal support
      (progesterone or human chorionic gonadotropin supplements) have been used to
      improve the live birth rate in recurrently aborting women. Each may modulate the
      balance between Th1 and Th2 cytokines. Th2 cytokines are thought to benefit the
      developing embryo by enhancing placental growth and function, and possibly by
      preventing inappropriate apoptosis. Although neither hormonal support nor
      immunopotentiation have proved to be beneficial, no trial has limited itself to
      pregnancies that are karyotypically normal. This review assesses fetal structural
      anomalies in humans and laboratory animals as causes of pregnancy loss, the role
      of cytokines in those anomalies and the role of immunomodulation and hormones in
      modifying these effects.

PMID- 11826773
TI  - [Antiretroviral treatment of HIV infections in 2001].

PMID- 11826774
TI  - [Anthrax as biological weapon].

PMID- 11826775
TI  - [How to reduce the number of involuntary admissions?].

PMID- 11826776
TI  - [Knowledge concerning the sequelae of torture].

PMID- 11826777
TI  - [Psychological treatment in attempted suicide].

PMID- 11826778
TI  - [By which measures can a good treatment of gastrointestinal hemorrhage be
      assured?].

PMID- 11826779
TI  - [Can case-mix explain differences in involuntary admissions?].
AB  - BACKGROUND: The proportion of patients admitted involuntarily varies considerably
      among Norwegian psychiatric hospitals. We tested the hypothesis that these
      variations are the result of differences in case-mix. MATERIAL AND METHODS: The
      observed differences in involuntary admissions to Norwegian psychiatric hospitals
      were compared to those expected on the basis of their case-mix, as predicted by
      our multivariate model (multinomial logistic regression). The material was based
      on a cross-sectional registration of hospitalized patients in Norwegian
      psychiatric hospitals as of 1 November 1999. Thirty-two hospitals (all Norwegian
      hospitals that take involuntary admissions) supplied data on a total of 1,500
      patients. RESULTS: The analysis shows that a large amount of the observed
      variation in involuntary admissions is related to differences in case-mix.
      However, for patients involuntarily admitted for observation, the case-mix was
      found to have less explanatory effect. Age, sex, previous admissions and
      diagnoses were used to operationalize hospital case-mix. INTERPRETATION: The
      analysis also indicated that other explanatory factors should be explored, such
      as differences in admission threshold and in medical decision in explaining
      variation in involuntary psychiatric admissions.

PMID- 11826780
TI  - [Rehabilitation of patients with chronic mental illness].
AB  - BACKGROUND: In Norway, the follow-up of patient with severe mental illness was
      redefined in the early 1990s. The number of inpatient beds in psychiatric
      hospitals was reduced and new methods for rehabilitation and follow-up tried out.
      In 1994, Vindern community psychiatric centre set up a special outpatient team
      for the follow-up of this group of patients. The aim of this study is to give an
      account of the status of these patients and to evaluate the rehabilitation
      programme. MATERIAL AND METHODS: All 181 patients admitted for follow-up by the
      team were included in the study. Data were drawn from yearly questionnaire
      surveys conducted between 1994 and 1999. RESULTS: 118 (65%) patients were
      diagnosed with schizophrenia; 32 (18%) had a personality disorder. 93 (51%) were
      readmitted to hospital during the five years of follow-up. Drug abuse was a
      problem for 58 (32%). 114 (63%) received a disability pension. Over the period,
      39 patients were transferred to follow-up in primary care. INTERPRETATION:
      Chronic mentally ill patients are a heterogeneous population. Though they have a
      long history of contact with psychiatric health services, they continue to live
      with a heavy burden of symptoms and dysfunction. The number of patients with
      personality disorders was greater than expected. The course, duration and
      severity of their illness was much like that of the schizophrenics.

PMID- 11826781
TI  - [Torture survivors in Norway--physician's responsibility].
AB  - BACKGROUND: Many political refugees who seek asylum in Norway have been
      imprisoned and subjected to torture. This review is based on the author's
      personal experience since 1976. MATERIAL AND METHODS: 44 men (22-45 years of age)
      and 9 women (23-32 years of age), all of them exposed to physical torture, were
      included in the study. The methods of torture are described. They were all given
      a full clinical examination by the author, including photos of possible injuries.
      RESULTS: The survivors showed physical and sexual sequelae, for instance multiple
      fractures of bones and teeth, tinnitus, broken testicles. INTERPRETATION: In my
      opinion, the most important therapist for torture victims is their general
      practitioner, who should work with nurses, physiotherapists, dentists and
      psychologists.

PMID- 11826782
TI  - [EEG after sleep deprivation in patients with suspected epilepsy].
AB  - BACKGROUND: The purpose of this study was to investigate to what extent sleep
      deprivation provokes epileptiform discharges in EEG in patients with suspected
      epilepsy. MATERIAL AND METHODS: Data from 189 adults and children with
      unspecified seizures who had had EEG after sleep deprivation were evaluated
      retrospectively. Previous standard EEGs were without epileptiform discharges. The
      patients' final diagnosis were collected from the medical records. RESULTS: 13%
      of the patients demonstrated epileptiform activity in their sleep deprivation
      EEG, and significantly more epileptiform activity was found in patients with
      generalized tonic-clonic seizures and absences. None of the patients with a
      history of syncope showed epileptiform activity. The activation rate was higher
      in patients with an abnormal standard EEG compared to those with a normal
      standard EEG. The sensitivity of sleep deprivation EEG in this study was 35%,
      specificity 98% and positive predictive value 92%. INTERPRETATION: Sleep
      deprivation EEG seems to have greatest diagnostic value in patients with
      generalized tonic-clonic seizures, absences and abnormal standard EEG.

PMID- 11826783
TI  - [Anemia and neutropenia in primary empty sella syndrome].
AB  - BACKGROUND: A 64-year-old man was admitted to our hospital with significant
      weight loss and symptoms of fatigue. He had normocytic anaemia and absolute
      neutropenia in peripheral blood. MATERIAL AND METHODS: Further haematological and
      endocrinological investigations were performed. RESULTS: Bone marrow aspiration
      and biopsy showed dysplastic signs. Immunophenotyping and cytogenetics did not
      provide evidence of primary haematological disease. Endocrinological testing
      demonstrated secondary adrenal insufficiency. Magnetic resonance imaging of the
      sella turcica showed an empty sella. Cortisol substitution eliminated the
      symptoms of the patient and normalised his peripheral blood values. The disturbed
      maturity and hypoplasia of the bone marrow were also normalised. INTERPRETATION:
      Normalisation of haematopoiesis after cortisol substitution indicates that
      cortisol plays an important role in the regulation of haematopoiesis. Primary
      empty sella syndrome with isolated ACTH cortisol deficiency is a very rare cause
      of disturbed haematopoiesis.

PMID- 11826784
TI  - [Assessment of the need of 24-hour availability of endoscopy].
AB  - BACKGROUND: Endoscopy is the cornerstone of the diagnosis and treatment of acute
      conditions in the upper part of the gastrointestinal tract. The need for 24-hour
      availability of gastroscopy for these conditions has not previously been
      assessed. MATERIAL AND METHODS: We assessed the need for emergency gastroscopy in
      cases of acute upper gastrointestinal bleeding and obstruction by foreign bodies.
      The assessment was made by a gastroenterologist before gastroscopy was performed,
      and was based on the available clinical data for the period lasting from
      admission to hospital to the time of examination. RESULTS: A total of 162
      patients were referred and examined. About half of them arrived at the hospital
      outside working hours. Of these, 47% were assessed as being in need of emergency
      gastroscopy. We therefore found that emergency gastroscopy outside working hours
      was needed twice a month per 100,000 people. INTERPRETATION: Round-the-clock
      endoscopy should be available at acute-care hospitals in the same way as other
      emergency help.

PMID- 11826785
TI  - [Usefulness of SPECT and MRI in the diagnosis of atypical parkinsonism].
AB  - BACKGROUND: Clinico-pathological studies have shown that only three out of four
      patients with parkinsonism have idiopathic Parkinson's disease. In patients with
      so-called Parkinson plus syndrome, the degeneration in the brain is more
      widespread and the variety of neurological signs greater than in Parkinson's
      disease. The differentiation of these syndromes from Parkinson's disease can be
      difficult. Single photon emission computed tomography (SPECT) and magnetic
      resonance imaging (MRI) can be of value in the differential diagnosis of
      parkinsonism. MATERIAL AND METHODS: We present three patients with atypical
      parkinsonism in whom MRI and SPECT with beta-CIT and epidepride was performed in
      addition to the clinical evaluation. RESULTS: The three patients all had a
      rapidly developing symmetric akinetic-rigid syndrome that responded poorly to
      levodopa. MRI showed findings regarded as typical for multiple system atrophy in
      two patients, but only nonspecific findings in the third patient. SPECT with beta
      CIT showed a pronounced bilateral and relatively symmetric reduction in the
      striatal dopaminergic activity in all patients. SPECT with epidepride showed a
      clearly reduced striatal D2-receptor binding bilaterally in only one of the
      patients. INTERPRETATION: In patients with atypical parkinsonism, MRI and SPECT
      with beta-CIT and epidepride can give valuable support to the clinical diagnosis
      of a Parkinson plus syndrome.

PMID- 11826786
TI  - [Injection therapy of trigger finger].
AB  - BACKGROUND: Since 1996 we have treated patients with trigger finger with
      corticosteroid injection as an alternative to surgery, on the basis of good
      results from this treatment reported in the literature. We wished to evaluate the
      results. MATERIAL AND METHODS: 27 patients with 32 trigger fingers were treated
      with corticosteroid injection. Two injections had been used in 17 fingers. The
      patients were contacted by mail or telephone median 4 years and 2 months (range
      29-56 months) later, and patients with persistent pain were examined clinically.
      RESULTS: 12 fingers had been operated by the time of the follow-up. 14 fingers
      were reported to be quite normal, one gave slight discomfort, four were still
      painful, but less so than before injection, and one was still as bad as before
      injection. Two of these patients had painful carpometacarpal arthrosis.
      INTERPRETATION: We suggest that corticosteroid injection should be tried in
      patients with trigger finger.

PMID- 11826787
TI  - [Alf Brodal--the great brain scientist].
AB  - The use of scientific methods in the investigation of the central nervous system
      began at the beginning of the twentieth century, as gifted scientists like Gustav
      Adolf Guldberg (1854-1908), Fridtjof Nansen (1861-1930), and Georg Herman Monrad
      Krohn (1884-1964) took up their research work. Dr Monrad-Krohn's renowned
      textbook, the so-called "Blue Bible", appeared in 1914 and enhanced the
      reputation of Norwegian science among specialists internationally. More than any
      other Norwegian scientist, Professor Alf Brodal (1910-88) brought brain research
      to new heights. This article presents a portrait of him in relation to his area
      of research.

PMID- 11826788
TI  - [Choice of triptan in migraine].

PMID- 11826789
TI  - [Antiviral therapy of HIV infection in adults].
AB  - BACKGROUND: Great progress has been made in antiviral treatment of HIV disease
      over the last few years. MATERIAL AND METHODS: The paper is based on relevant
      literature and our own experience in the largest HIV clinic in Norway. RESULTS
      AND INTERPRETATION: Generally speaking, therapy with at least three active drugs
      is necessary in order to obtain maximum viral suppression. It is not established
      what constitutes the best starting-point for therapy, or what combination of
      drugs is the most efficacious. Treatment should be initiated before clinical
      immunodeficiency develops. All patients with CD4 counts < or = 0.2 x 10(9)/l
      should be offered treatment. The initial regimen should be either two nucleoside
      analogues and one or two protease inhibitors, or two nucleoside-analogues and
      efavirenz. In order to avoid resistance and treatment failure, the patient should
      be thoroughly informed before and during treatment about the importance of good
      compliance.

PMID- 11826790
TI  - [HIV-1 resistance against antiretroviral agents].
AB  - BACKGROUND: Failure of antiretroviral drugs to completely suppress HIV-1
      replication inevitably leads to selection of drug-resistant variants. Emergence
      of drug resistance plays a major role in limiting the long-term success of
      antiretroviral therapy. MATERIAL AND METHODS: From August 1998 until April 2001,
      a total of 183 samples from 152 patients were analysed for HIV-1 drug resistance
      using genotypic analysis. RESULTS: Mutations associated with resistance were
      found in virus from 112 patients who received antiretroviral therapy. Mutations
      were frequently identified in the reverse transcriptase gene and to a lesser
      extent in the protease gene. Mutations associated with reduced drug
      susceptibility or polymorphisms were identified in 22 treatment naive patients.
      In addition, resistance mutations were observed in three out of eight patients
      with a recent infection. INTERPRETATION: Genotypic resistance testing is a
      valuable tool for rational decision-making when the current therapy is failing.
      In addition, patients with a recent HIV-1 infection should be tested for the
      surveillance of transmission of drug-resistant genotypic variants.

PMID- 11826792
TI  - [Risk assessment in connection with violent behavior--use of check lists].

PMID- 11826791
TI  - [Tuberculosis among HIV-infected persons in Norway].
AB  - BACKGROUND: HIV-infected persons have a considerably higher risk of developing
      active tuberculosis than immunocompetent individuals. Tuberculosis is the only
      opportunistic infection among HIV-infected persons that presents a potential
      health risk to the general population. MATERIAL AND METHODS: We present a review
      on this topic based on relevant literature and clinical experience. RESULTS:
      Treatment options are limited because of interactions between rifamycins and
      protease inhibitors and non-nucleoside analogues. When concomitant therapy
      against HIV infection and tuberculosis is indicated, we suggest a first-line
      regimen of rifabutin combined with either indinavir or nelfinavir. For patients
      without severe immunodeficiency, anti-retroviral therapy can be postponed until
      the end of the initial phase of the anti-tuberculosis treatment. INTERPRETATION:
      Treatment of concurrent HIV infection and tuberculosis is complex and may involve
      multiple drug regimens. Treating the latent infection could in many cases prevent
      active tuberculosis. All HIV-infected persons should be evaluated with respect to
      active tuberculosis and latent infection.

PMID- 11826793
TI  - [Analysis of prothrombin time in primary health care].

PMID- 11826794
TI  - [Mentally ill parents--what to do with the children?].

PMID- 11826795
TI  - [Ultrasound in general practice].

PMID- 11826796
TI  - [Physiotherapy after stroke].

PMID- 11826797
TI  - [Methadone and thyroid disorders].

PMID- 11826798
TI  - [Relatives--problem or resource?].

PMID- 11826799
TI  - [Treatment of warts and other serious diseases].

PMID- 11826800
TI  - Biological and novel therapies for inflammatory bowel disease in children.
AB  - During the past decade, a tremendous wealth of information regarding the
      pathogenesis, genetics, and therapy of IBD has been discovered. Judging by the
      number of new publications published every month in scientific journals and the
      great enthusiasm at scientific meetings, this outstanding pace surely will
      continue. In the near future, clinicians may be able to classify IBD into several
      subtypes depending on patients' cytokine and gene profiles. For example, two
      groups of researchers recently have identified mutation in the NOD2 gene, which
      is associated with susceptibility to CD. This identification may allow the
      clinician to better predict outcome and response to medical therapy. At the same
      time, several promising new therapies are being investigated. Technologic
      advances will continue to result in the development of potent and specific agents
      that will control and possibly correct the abnormal inflammatory processes
      responsible for pediatric IBD.

PMID- 11826801
TI  - Newer components of enteral formulas.
AB  - The past decade has seen a paradigm shift in the goals of nutritional care from
      basic delivery of macronutrient calories to the provision of specific nutrients,
      which, in addition to supporting growth, have health and disease modulating
      effects. The appreciation of the central role of nutrition in heath and disease
      may lead to increased use of a new array of diets that are more specific for
      underlying health and disease pathophysiologic processes. An improved
      understanding of disease-specific pathophysiology, and limited but promising data
      from ongoing clinical trials, are fueling this positive change. Therefore, a
      greater understanding of rationale for the newer products may lead to improved
      nutritional and clinical care during health and disease.

PMID- 11826802
TI  - Probiotics in health and disease in the pediatric patient.
AB  - Probiotics are truly a timeless concept. Initially standard components of the
      human diet, potentially beneficial bacteria and yeast have been eliminated
      systematically through modern methods of preparing and preserving foods. Although
      the concept of probiotics is not new, the science of probiotics is in its
      infancy. Only recently have techniques been developed to identify, culture, and
      produce the probiotics that are suitable for medical use consistently.
      Furthermore, the potential uses for these organisms may extend far beyond what
      originally was thought. In no way should probiotics be thought of as a panacea
      for the diseases described earlier; however, when used appropriately, they
      represent a potentially beneficial adjunct to other proved therapies and have the
      added benefit of providing a stabilizing influence on the delicate balance
      between the ecosystem that consists of the human and its flora.

PMID- 11826803
TI  - Current concepts in pediatric bone disease.
AB  - It is widely believed that osteoporosis prevention may be best accomplished
      during childhood and adolescence, when bones are growing rapidly and are most
      sensitive to environmental influences, such as diet and physical activity. For
      children with chronic diseases, a variety of factors may influence normal bone
      mineralization, including altered growth, delayed maturation, inflammation,
      malabsorption, reduced physical activity, glucocorticoid exposure, and poor
      dietary intake. In healthy children, maintaining adequate levels of calcium
      intake, serum vitamin D, and weightbearing physical activity may be sufficient to
      prevent osteoporosis later in life. Far less is known about effective prevention
      and treatment of poor bone mineralization in children with chronic illness, such
      as CF or CD. Osteoporosis prevention and intervention measures during childhood
      are limited by the paucity of reference data on bone mineralization. Although it
      is widely recognized that puberty, skeletal maturation, and body size influence
      BMC and bone density, no reference data for bone mineralization are scaled to
      these important measures. In children with chronic disease with delayed growth
      and maturation, the creation of such reference data is of paramount importance.
      In addition, the dynamic changes that occur during growth and maturation in the
      structural characteristics of trabecular and cortical bone and the development of
      the bone-muscle unit may influence current and future fracture risk. Further
      research is needed to characterize these changes and their use in the assessment
      of bone health and fracture risk in children. Only then can the impact of
      treatment strategies be appreciated fully.

PMID- 11826804
TI  - Childhood obesity.
AB  - The pediatrician's approach to overweight was best summarized by Bruch 25 years
      ago: The pediatrician plays an important role in the prevention of obesity. From
      birth on, feeding a child always involves a dual task--namely, offering food in
      appropriate amounts and gearing it to the child's expression of his needs. Only
      in this way can he develop discriminating awareness and become active in
      establishing self-regulation.... If a child is fed when he is hungry, played with
      when he needs attention, and encouraged to be active when he is restless, he is
      not likely to grow up inhibited and passive or overstuffed and helpless, unable
      to control his eating because every discomfort is misinterpreted as a need to
      eat.

PMID- 11826805
TI  - Diagnosis and management of mitochondrial diseases.
AB  - Mitochondrial dysfunction should be considered in the differential diagnosis of
      any progressive multisystem disorder. The diagnosis is most challenging when only
      one symptom is present. In contrast, the diagnosis is easier to consider when two
      or more seemingly unrelated symptoms are present, involving more than one organ
      system. It is important to consider the diagnosis of a mitochondrial disorder
      when dealing with an unexplained association of symptoms, with an early onset and
      progressive course involving seemingly unrelated organs. The investigation can be
      relatively straightforward if a person has a recognizable phenotype and if it is
      possible to identify a known pathogenic mtDNA mutation. The difficulty arises
      when no known mtDNA defect can be found or when the clinical abnormalities are
      complex and not easily matched to those of more common mitochondrial disorders.
      In summary: A full mitochondrial evaluation often is warranted in children with a
      complex neurologic picture or a single neurologic symptom and other system
      involvement. When the presentation is classic for a maternally inherited
      mitochondrial syndrome, such as MELAS, MERRF, or Leber's hereditary optic
      neuropathy, appropriate mtDNA studies should be obtained first. When the clinical
      picture is classic for a nuclear DNA inherited syndrome and the gene or linkage
      is known, such as MNGIE, the clinician should proceed with genetic studies. When
      the clinical picture is nonspecific but highly suggestive of a mitochondrial
      disorder, the clinician should start with plasma or CSF lactic acid, ketone
      bodies, plasma acylcarnitines, and urinary organic acids. If these studies are
      abnormal, the clinician should proceed with muscle biopsy and assessment of the
      respiratory chain enzymes. Normal plasma or CSF lactic acid does not rule out a
      mitochondrial disorder.

PMID- 11826806
TI  - Molecular basis of neonatal cholestasis.
AB  - At present, specific evidence regarding the molecular mechanisms of neonatal
      cholestasis is limited. The recent explosion in the understanding of the
      molecular physiology of bile formation has been fueled by the discovery of
      several genes that are involved in familial cholestasis. The ever-growing
      understanding of the functional immaturity of the neonatal liver is sure to be
      enhanced by the study of the ontogeny of important hepatobiliary transporters as
      they are discovered. The understanding of the functional differences between the
      immature and mature liver is key to the understanding of neonatal cholestasis.

PMID- 11826807
TI  - Motility disorders. Diagnosis and treatment for the pediatric patient.
AB  - Motility disorders are common in children and may affect any area of the GI
      tract. The past decade has brought significant advances in the understanding of
      motility disorders in pediatrics. More sophisticated testing techniques have
      helped to differentiate normal from abnormal motility in children of different
      ages. Manometry now may be used to clarify the pathophysiologic defect underlying
      chest pain, dysphagia, rumination, gastroparesis, chronic intestinal pseudo
      obstruction, and colonic neuromuscular disorders. Motility testing also may be
      used to identify the motor defect responsible for persistence of symptoms after
      surgery for GER or HD. New investigational techniques and prokinetic agents
      likely to be available in the future also were discussed.

PMID- 11826808
TI  - Recurrent abdominal pain in children.
AB  - Functional abdominal pain can occur in a well-defined clinical entity (e.g., IBS)
      or as a part of a poorly defined clinical syndrome. Although the clinician may
      feel compelled to exclude disease in all cases, the authors suggest that it is
      more appropriate to take a biopsychosocial approach. In so doing, there can be an
      appreciation of the close interaction of the gut and the brain, allowing the
      child, family, and physician the opportunity to address the pain on many levels.
      Although the parameters set forth by the pediatric ROME II committee have
      facilitated the authors' description of these disorders greatly, basic research
      likely will further delineate biochemical processes in the enteric and central
      nervous systems that will expand therapeutic horizons.

PMID- 11826809
TI  - Food allergy. Mechanisms, diagnosis, and management in children.
AB  - We eat approximately two to three tons of food in our lifetime, but most people
      do not have an adverse reaction to foods. Many people believe that they have an
      allergic reaction to foods; however, the actual incidence confirmed by history
      and challenges suggests a prevalence rate closer to 2% to 8% in young infants and
      less than 2% in adults.

PMID- 11826810
TI  - Feeding disorders in infants and children.
AB  - Feeding disorders are common in infants and children. Multiple interacting
      behavioral, anatomic, and functional factors all can impact on the feeding
      process, making the evaluation and treatment of pediatric disorders complex and
      challenging. Knowledge of the normal process of feeding and swallowing, a careful
      history, observation of the patient during a feeding session, and selected tests
      usually provide an understanding of the underlying cause of feeding difficulties.
      Treatment of underlying pathology and careful balancing of the risks and benefits
      of oral feeding underlie the selection of an optimal management strategy.

PMID- 11826811
TI  - [Turbulence and high intensity transient signals (HITS) as a parameter for
      optimum orientation of mechanical heart valves].
AB  - BACKGROUND: In previous studies, the impact of valve orientation on the
      hemodynamic performance of mechanical aortic valves has been demonstrated. This
      study investigates Turbulence (RNS values) and High Intensity Transient Signals
      (HITS) as a new and objective parameter for hemodynamics in various orientations
      of Medtronic Hall (MH) and St. Jude Medical (SJM) aortic valves. METHODS:
      Rotation devices carrying a MH or SJM valve were implanted into four pigs. The
      device allowed valve rotation without reopening the aorta. In various
      orientations, turbulent shear stresses (RNS values) and HITS were measured.
      RESULTS: RNS and HITS changed for both valve designs in the different
      orientations, with superior results for the MH in the hemodynamically best
      orientation. Downstream turbulence (RNS) and HITS varied in the same direction,
      but a one to one correlation was not observed. CONCLUSIONS: RNS and HITS vary
      with respect to valve orientation and design with superior results for the
      tilting disc valve. Both MH and SJM valves showed lower turbulence and HITS
      counts in their hemodynamically best orientations. HITS were related to
      downstream turbulence and the hemodynamic performance of the mechanical aortic
      valves.

PMID- 11826812
TI  - [Marfan syndrome and heart valve diseases].
AB  - Marfan syndrome is a hereditary disease of the connective tissue with increased
      mortality mostly due to changes of the cardiovascular system. We describe our
      experience with the surgical treatment of 243 patients with Marfan syndrome and
      cardiovascular complications. We report the results of treatment of annulo-aortal
      ectasia using the classical surgical methods of Bentall DeBono and Cabrol and the
      method for preservation of the native aortic valve and concomitant surgery of the
      mitral valve. Reconstruction or replacement of the mitral valve is mainly based
      on the classical indications. Preservation of the native aortic valve and
      reconstruction of the mitral valve in patients with Marfan syndrome is possible
      but the long-term results are still unknown.

PMID- 11826813
TI  - [Current recommendations for prevention of thromboembolism in patients with heart
      valve prostheses].
AB  - Within the last few years, marked progress has been made in the prevention of
      thromboembolic events in patients with mechanical heart valves. Thus, therapy has
      become more effective and is associated with less risk. This includes a number of
      developments like the introduction of the internationalized, normalized ratio
      (INR) for determination of the intensity of anticoagulation, the concept of a
      risk factor-adjusted, prosthesis specific, individualized indication for and
      intensity of anticoagulation and the possibility for self-determination of
      anticoagulation intensity by the patient. Prospective, randomized studies on the
      effect of different intensities of anticoagulation allowed definitions of
      individualized anticoagulation target levels and were the basis for guidelines on
      clinical management of anticoagulation. In spite of this progress, thromboembolic
      complications and anticoagulation associated bleedings are still the most
      frequent complications after valve replacement. The guidelines published by the
      professional societies on anticoagulation should be followed more closely in
      daily clinical practice. The management of oral anticoagulant treatment can be
      improved by following the concept of a risk factor-adjusted indication for and
      intensity of oral anticoagulant treatment as well as the use of the INR for
      monitoring the intensity of anticoagulation. Intensive education of the patient,
      implementation of self-testing by suitable patients and increasing the frequency
      of testing can further contribute to improvement.

PMID- 11826815
TI  - [Anticoagulation of pregnant women with mechanical heart valve prostheses].
AB  - Patients with a mechanical heart valve prosthesis (MHVP) are usually
      anticoagulated with oral anticoagulants (OAC) to prevent thromboembolic
      complications. Considering the paucity of published data, the management of women
      with MHVP of childbearing age, who wish to become pregnant, still remains
      difficult and complicated. OAC may cause embryopathy during the first trimester,
      while neurologic complications, stillbirth and fetal death may appear during the
      second and third trimester. While the application of unfractionated heparin (UFH)
      in pregnant patients with MHVP may fail to prevent thromboembolic complications
      even with therapeutic dosage, only little is known about the application of body
      weight adjusted therapeutic dosages of low molecular weight heparin (LMWH). We
      report on 8 female patients, 7 with MHVP, one with atrial fibrillation, who were
      treated with LMWH during the whole pregnancy. No malformations or major bleeding
      complications were observed, no valve thrombosis or thromboembolic complications
      occurred. Three patients developed moderate heart failure during the third
      trimester, which resolved after treatment. In three patients, cesarean section
      was necessary, while the other five patients delivered spontaneously. Therefore,
      anticoagulation with body weight adjusted LMWH seems to be an alternative, safe
      and efficient treatment for pregnant women with MHVP. Prospective, randomized
      studies are needed to further evaluate this new therapeutic approach. The
      underlying heart disease represents a serious comorbid condition that requires
      continuous interdisciplinary monitoring.

PMID- 11826814
TI  - [INR self-management after mechanical heart valve replacement: ESCAT (Early Self
      Controlled Anticoagulation Trial)].
AB  - Severe thromboembolic and hemorrhagic complications following mechanical heart
      valve replacement essentially occur due to intense oral anticoagulation and
      fluctuating individual INR values around the target range. INR self-management
      can help to minimize these fluctuations. Beginning this therapeutic control
      immediately after mechanical heart valve replacement further reduces
      anticoagulant-induced complications. Included in the study were 1200 patients.
      The quality of oral anticoagulation also improved through INR self-management.
      Over an observation period of two years, nearly 80% of INR values recorded by the
      patients themselves were within the target therapeutic range of 2.5-4.5. This
      corresponds to a high significance of p < = 0.001 in favor of INR self
      management. Only 64.9% of INR values monitored by family practitioners were
      within the desired range. The results differed slightly in quality between
      patient groups with different levels of training (comprehensive, secondary
      modern, grammar with or without university). Of patients trained in INR self
      management following mechanical heart valve replacement, 91.7% maintained their
      competence in this technique throughout the entire follow-up period. Only 8.3% of
      those trained immediately after surgery were unable to continue with INR self
      management.

PMID- 11826816
TI  - [Current diagnosis and therapy in heart valve diseases].
AB  - We present a survey of the current standard in diagnosis and therapy of the most
      frequent heart valve lesions. During the last 50 years there has been a dramatic
      shift concerning the etiology of valve lesions with a rise of the age-dependent
      degenerative towards rheumatic valve diseases. The aim of the diagnostic
      evaluation of valve lesions is primarily the clinical and hemodynamic grading of
      the severity of the valve disease, the recognition of relevant coexisting cardiac
      and extracardiac diseases and furthermore, an optimal timing of surgery in close
      correlation with the cardiac surgeons.

PMID- 11826817
TI  - [The use of cross-sectional imaging modalities in the diagnosis of heart valve
      diseases].
AB  - Exact visualization of valve morphology seems to be possible with the cross
      sectional imaging modalities, magnetic resonance imaging (MRI) and the recently
      introduced technique of multi-detector computed tomography (MDCT). These
      techniques are used, if other non-invasive imaging modalities, like
      echocardiography, fail or provide only insufficient information. This commonly
      occurs in the assessment of right ventricular valves. Quantification of valve
      stenosis is possible by calculating valve orifice area, which can be performed
      with MRI and MDCT. An estimation of the instantaneous peak gradient can only be
      achieved by MR flow measurements. MR flow measurement is a reliable method to
      quantify the degree of mild to moderate stenoses. Quantification of valve
      regurgitation is possible by measurement of the regurgitation fraction with MR
      flow measurements as well as with MR volumetry/CT volumetry. But only the MR flow
      measurement is suitable for the quantification of valve regurgitation in patients
      with multiple valves involved or cardiac shunting. MRI and probably MDCT are the
      most reliable methods in the evaluation of ventricular volumes and therefore
      suitable for the follow-up in patients with valvular heart disease, because
      changes in volumes are important for therapeutic decisions in these patients. The
      crucial advantages of MRI compared to CT in the diagnostic of valvular heart
      diseases however are the absence of radiation exposure, the possibility of
      quantitative evaluation of valves function using flow measurements and the higher
      temporal resolution as compared to MDCT.

PMID- 11826818
TI  - [Prophylaxis of bacterial endocarditis].
AB  - An effective prophylaxis against bacterial endocarditis is necessary in patients
      at risk. In all medical specialities, a lack of information about the importance
      concerning an antibiotic prophylaxis of bacterial endocarditis remains. Among
      other institutions the American Heart Association has updated recommendations for
      the prevention of bacterial endocarditis in order to more clearly define when
      prophylaxis is or is not recommended, improve practitioner and patient
      compliance, and reduce cost as well as potential side effects.

PMID- 11826819
TI  - [Long-term results of the surgical treatment in acute aortic valve endocarditis].
AB  - Late results after surgery for acute infectious aortic endocarditis using
      allografts are compared with those achieved with bioprostheses or mechanical
      heart valves. Cryopreserved allografts were used in 74 (22%) and prosthetic heart
      valve in 262 out of 336 (78%) patients presenting acute aortic endocarditis.
      Prosthetic (p = 0.001) and destructive endocarditis (p = 0.001) were more
      frequent in patients receiving allografts. Mean follow-up time was 6.6 +/- 4
      years (range, 3 to 28 years). The 30-day-mortality was 19% for allograft patients
      and 6% for those receiving prosthetic heart valves (p = 0.002). Early
      reoperation, postoperative renal failure and sepsis did not differ between
      groups. After 20 years, actuarial survival was 60% for mechanical heart valves,
      44% for bioprosthesis and 38% for allografts (p = 0.003), reoperation was
      unnecessary in 52% of mechanical heart valves and 10% of bioprostheses and
      allografts (p = 0.0007). Acute infection at the time of operation (p = 0.0001),
      redo surgery (p = 0.0006), staphylococci (p = 0.0003), older age (p = 0.004) and
      mitral valve involvement (p = 0.004) were risk factors for late death,
      irrespective of preoperative antibiotic treatment and type of prosthesis used. A
      longer bypass and aortic cross-clamp time predicted early (p = 0.0001) and late
      survival (p = 0.0001), independently. Destructive aortic endocarditis has a poor
      long-term outcome irrespective of the use of allografts. Acute infection at the
      time of surgery predicted early and late death; however, surgery is indicated
      prior to secondary involvement of the mitral valve. The duration of preoperative
      antibiotic treatment did not affect outcome. A thorough surgical technique
      directly influences early and late survival.

PMID- 11826820
TI  - Etiology of degenerative disease of the tri-leaflet aortic valve: a simple
      explanation for a complex problem.
AB  - Risk factors for both atherosclerotic aortic wall disease and degenerative
      disease of the tri-leaflet aortic valve are very similar if not identical. This
      correlation grows even stronger as the person advances in years. Because of this,
      it is the prevailing view that sclerosis of the tri-leaflet aortic valve is a
      disease similar in etiology with sclerosis of the aortic wall. In other words,
      degenerative aortic valve disease is atherosclerosis of the aortic valve. Our
      studies challenge these views. The aortic valve is a functional assembly composed
      of the three cusps, corresponding sinuses, and the sinotubular junction,
      characterized not only by morphological features but also its functional
      properties, which together create an environment that is optimal for distribution
      of diastolic pressure load, and assures proper and timely valve opening and
      closure. Our experiments also demonstrate that loss of aortic wall compliance at
      the level of the sinuses leads to significant flexion stress in the aortic
      leaflets and it is likely to start a chain of events, which begins with
      mechanical damage to the leaflet microstructure then continues to more evident
      sclerosis, and finally ends in gross distortion and/or calcification of the
      cusps. The loss of the "pull-and-release" process may also play a part in
      disintegration of bioprosthetic valves and in degeneration of native aortic
      valves encased in non-compliant prostheses.

PMID- 11826821
TI  - [Mechanical versus biological heart valves].
AB  - Since the first successful heart valve replacement procedures were performed in
      the 1950s, a multitude of different heart valves have been developed and
      implanted. This review offers a structured overview of the most important
      mechanical and biological heart valves with special regard to the individual
      indications of mechanical versus biological heart valve replacement and to
      possible postoperative complications.

PMID- 11826822
TI  - [Patient-adapted valve selection: biological vs. mechanical heart valve
      replacement in aortic valve diseases].
AB  - Since the first aortic valve replacement performed by Harken in 1960, the
      operation of aortic valve disease by replacing the native valve with a heart
      valve prosthesis has become one of the most frequently performed procedures in
      cardiac surgery. For valve replacement there are biological (xenografts and
      homografts) and mechanical heart valve prostheses available. When choosing the
      most suitable prosthesis the limited durability of a biological prosthesis and
      the risks of lifelong anticoagulation for a mechanical prosthesis have to be
      balanced. In this article the indication for operation of aortic valve stenosis
      and aortic regurgitation are discussed first. Based on the literature of the last
      2 years the advantages and disadvantages of mechanical and biological heart valve
      prostheses (xenograft, homograft and ROSS procedure) are discussed. In addition
      rarely used techniques like aortic valve reconstruction are presented. Due to the
      fact that a biological prosthesis has a durability of 12-15 years and the risk of
      bleeding complications under anticoagulation grows with increasing age, the
      choice of a biological prosthesis can be recommended from the age of 65 years.
      Results of long-term studies at to whether this limit can be diminished by using
      a stentless biological prosthesis have to be awaited.

PMID- 11826823
TI  - [Risk of perioperative mortality and complications following biological aortic
      valve replacement in elderly patients: stented vs. unstented prostheses].
AB  - Recently published studies suggest that the hemodynamic advantage of stentless
      bioprostheses in comparison to stented bioprostheses positively influence the
      long-term survival after aortic valve replacement. However, the more complex and
      time consuming implantation technique may increase the risk of operative death.
      Between April 1996 and September 2000, 201 patients with the mean age of 75 +/- 5
      years underwent aortic valve replacement (AVR) with a stentless Medtronic
      Freestyle Bioprosthesis (FP) and 166 patients with a mean age of 77 +/- 5 years
      received a stented Medtronic Mosaic Bioprosthesis (MP). Patients requiring
      concomitant procedures other than coronary artery bypass grafting (CABG) were
      excluded. The operative mortality was 3.5% after AVR with the FP and 6% after AVR
      with the MP. Multiple logistic regression analysis considering the different
      patient populations revealed no increased risk of operative death after AVR with
      FB (p = 0.46). Previously heart operations (p = 0.046) and emergency operation (p
      = 0.022) were risk factors for operative death after AVR with the biological
      bioprostheses. The risk for postoperatively neurological impairment (p = 0.15)
      and other complications (p = 0.46) was furthermore not increased after
      implantation of a Freestyle stentless valve. The risk of delayed mobilization (p
      < 0.001) was 2.4-fold increased for patients after AVR with the Freestyle valve.
      A positive influence on survival due to the implantation of a stentless Freestyle
      valve could not be shown within the observed period. However, in spite of the
      more complex and time-consuming operation technique, the risk of operative death
      and postoperative complications is not increased after aortic valve replacement
      with the stentless FB.

PMID- 11826824
TI  - [Multiple heart valve diseases: differential therapeutic considerations].
AB  - After more than 40 years of heart valve surgery, the indication for double valve
      procedures still represents a problem in the presence of an obviously leading
      single valve disease. If the isolated valves do not already represent a clear
      indication for surgery then this situation is the best example for a good deal of
      thought in cardiac surgery and discussion with competent cardiologists.

PMID- 11826825
TI  - [Timing of reoperation of degenerated aortic and mitral bioprostheses].
AB  - Reoperative surgery for degenerated aortic and mitral valve bioprostheses has a
      considerable mortality. This study compares life expectancy, mode of failure and
      predictors for emergency reoperation and reoperative mortality between
      degenerated aortic and mitral bioprostheses. A total of 265 bioprosthetic valve
      patients, 172 aortic and 93 mitral patients, were followed to assess the time
      period between first and redo valve replacement. Mean life expectancy for aortic
      bioprostheses was 10.4 +/- 4.3 (2 to 28.6) years, whereas it was 10.0 +/- 3.7
      (0.9 to 20) years for mitral bioprostheses (group M). Emergency reoperation had
      to be performed in 31/172 group A (18%) and 16/93 group M (17%) patients. In
      group A, the reoperative mortality was 5.2%; it was 1.4% for elective and 22.6%
      for emergency reoperation (p < 0.0001; OR = 20.3). Reoperative mortality in group
      M patients was 5.4% and did not differ between elective and emergency surgery.
      Group A patients who died at reoperation had higher transvalvular gradients
      before the first operation (p = 0.007), received smaller sized bioprostheses (p =
      0.03) and had a higher incidence of coronary artery disease (p = 0.001) and
      pulmonary artery hypertension (p = 0.009) acquired during the interval.
      Endocarditis being the reason for primary surgery (p = 0.004), postoperative
      pneumonia after the first procedure (p = 0.005), pulmonary artery hypertension (p
      = 0.0004), later recurrence of symptoms of valve degeneration (p = 0.04), acute
      onset of bioprosthetic regurgitation (p = 0.00002) and a lower left ventricular
      ejection fraction (p = 0.03) were risk factor for emergency surgery. There were
      no predictors of reoperative mortality identified in mitral valve patients. The
      life expectancy of aortic and mitral bioprostheses is acceptable even in a
      relatively young patient population (mean age 46 +/- 13 in group A and 45 +/- 12
      years in group M patients). Patients with degenerated aortic bioprostheses
      undergoing emergency reoperation have an extraordinary high reoperative
      mortality. They can be identified as patients who had a history of endocarditis
      and higher transvalvular gradients prior to the first operation, who received
      smaller sized bioprostheses and acquired coronary artery disease and pulmonary
      artery hypertension during the interval. Thus, emergency reoperation is
      preventable, increasing overall life expectancy of patients with bioprostheses.
      There were no risk factors for reoperative mortality identified in bioprosthetic
      mitral valve patients.

PMID- 11826826
TI  - Mitral valve repair versus mitral valve replacement.
AB  - Over the past 40 years mitral valve surgery has changed dramatically. After
      initial enthusiasm with the introduction of valve prostheses in the 1960s, a
      renewed interest in repair techniques began in the 1970s with the introduction of
      annuloplasty rings. These repair techniques revealed that the integrity of the
      subvalvular apparatus plays an important role in left ventricular function. When
      considering the major series comparing early and late results of mitral valve
      repair versus prosthetic mitral valve replacement, operative mortality rate is
      lower for patients with mitral valve repair. Long-term results also show a
      superior survival rate after mitral valve reconstruction. In addition, several
      problems can occur with the prosthetic valve, such as thromboembolism and
      endocarditis. All of these factors favor valve repair over replacement. The
      success of mitral valve repair depends on many factors: etiology of the mitral
      valve disease and the resultant pathomorphology of the valve, patient's
      circumstances such as age or contraindication for anticoagulation, and the
      experience of the surgeon. The decision whether to repair or replace the mitral
      valve depends on these factors. Data in the literature and in large collective
      databases reflect the advantages of mitral valve repair, with over 75% of current
      mitral valve surgeries being repairs. In the past 5 years the exposure of the
      mitral valve through a right lateral minithoracotomy using video assistance has
      developed into a widespread technique. This approach allows complex mitral valve
      repair as well as mitral valve replacement even with biological stentless
      prostheses, with decreased morbidity. The addition of radiofrequency ablation for
      restoration of sinus rhythm enhances the outcome after mitral valve surgery, and
      can also be easily performed through a minithoracotomy technique.

PMID- 11826827
TI  - [Surgery in terminal mitral valve diseases].
AB  - In the past few years both the spectrum of mitral valve diseases leading to
      surgery and the surgical techniques have changed. We present our experience with
      the preservation of the subvalvular apparatus when mitral valve replacement is
      performed. In addition to preservation of the subvalvular apparatus of the
      posterior mitral leaflet, five techniques of subvalvular preservation are
      described. We conclude that mitral valve replacement should always aim at
      preservation of the subvalvular structures. The surgical method of choice in
      cases of isolated mitral valve insufficiency is mitral valve reconstruction.
      Treatment of associated atrial fibrillation, preferably by radiofrequency
      ablation, should always be performed concomitantly. Surgery of the mitral valve
      represents a palliative operation in selected patients with terminal
      cardiomyopathy.

PMID- 11826828
TI  - [Replacement of the ascending aorta with aortic valve reimplantation:
      indications, technique and results].
AB  - The main cause of aortic valve insufficiency is a dilatation of the sinotubular
      junction in patients with an ascending aortic aneurysm. Morphologically preserved
      aortic valve cusps represent an ideal condition for preservation and
      reconstruction of the aortic valve with an simultaneous replacement of the
      ascending aorta with a Dacron graft. This report presents the results of 140
      patients, who underwent such surgery since 1993 in our institution. Indications
      for surgery, operative technique and different outcome parameters are discussed.
      Intra- and perioperative morbidity and mortality are low and quality of life
      excellent. Reoperation due to progressive aortic valve insufficiency was
      necessary in 2.1% of patients during follow-up. When compared with the standard
      operation (composite replacement utilizing a mechanical valve), patients with
      aortic valve reconstruction demonstrate similar results with regard to hospital
      stay and functional improvement. However, bleeding complications and
      thromboembolic events are significantly reduced in patients undergoing valve
      reconstruction. Due to these long-term results combined with excellent stress
      hemodynamics and improvement in LV function, aortic valve reconstruction
      currently represents our standard operative strategy in this patient group.

PMID- 11826829
TI  - [Perioperative complications after heart valve replacement].
AB  - These days, the majority of perioperative complications resulting from operations
      on heart valves are more a consequence of the increasing age and morbidity of the
      patients and, despite all cardiac surgical and intensive care innovations, are
      still more the effect of the procedure on the other organ systems of the patient
      than being purely of a surgical nature. The surgical short- and long-term results
      after heart valve operations are significantly influenced by the early detection
      and adequate management of these manifold complications.

PMID- 11826830
TI  - [Myocardial revascularization after pretreatment with the GPIIb/IIIa receptor
      blocker abciximab].
AB  - AIM: The present prospective study analysis whether preoperative abciximab
      treatment 1) increases perioperative risks, 2) alters the quality of the surgical
      treatment, 3) whether secondary organ complications occur and 4) whether and how
      the perioperative surgical management has to be modified. METHODS: The
      perioperative results of patients operated upon after preoperative abciximab
      treatment (n = 31, 1/1994-4/2000) were compared with an optimal control group
      (elective patients and no preoperative intervention in the hemostaseological
      system) and with other patients (elective, urgent, emergency operations)
      receiving different strategies of preoperative hemostaseological interventions (n
      = 926, 1/1994-4/2000). All patients were operated upon with a well-defined
      strategy (one surgeon). 1100 perioperative items/patient were prospectively
      recorded and analyzed. The 30-day and 6 month follow-up was complete. RESULTS:
      The mean time interval between end of abciximab therapy and onset of operation
      was 4.3 h (range: 36-0.5 h, median: 2 h). As compared with the optimal control
      group (n = 81), perioperative blood loss and the need for substitution of blood
      and blood products was increased. However, as compared with those patients
      receiving any type of preoperative intervention in the hemostaseological system
      (the majority of the patients), no difference was observed regarding
      intraoperative parameters (duration of extracorporeal circulation and of the
      operation) and postoperative results (neurological, renal complications,
      myocardial infarction, psychiatric disturbances, etc.) when abciximab patients
      were compared with the reference populations. No patient of the abciximab group
      died within 30 days or during the 6 month follow-up period. CONCLUSION: The data
      show that coronary artery bypass grafting can be performed with similar results
      in abciximab-pretreated patients as in patients with other types of preoperative
      anticoagulation. Only slight modifications of the surgical management are
      recommended. As indicated by similar use IMA-grafts the quality of surgical
      treatment was not reduced.

PMID- 11826831
TI  - [Electrophysiological characterization of connexin 40 deficient hearts--in vivo
      studies in mice].
AB  - Intercellular communication is not only mediated by extracellular transmitters,
      but also directly by gap junction channels. One channel is composed of two
      hexameric hemichannels which consist of six polypeptide subunits called
      connexines (Cx). In the mammalian heart the following connexines have been
      documented: Cx37, Cx40, Cx43, Cx45, Cx46, Cx50 and Cx57. The labeling by number
      represents the rounded, molecular mass of the amino acid sequences given in kD.
      If identical connexin-isotypes form both connexons of a gap junction channel,
      homotypic coupling exists and a homomeric gap junction channel is formed.
      Different connexin-isotypes within both connexons cause form heterotypic coupling
      and heteromeric gap junction channels. Each channel type has specific properties
      regarding permeability and electrical conductance. Beside a typical age-dependent
      alignment of gap junction channels on the surface of the cardiac myocytes,
      regional distribution of the different connexins is different at distinct parts
      of the mouse heart. Cx40 is not found in the ventricular working myocardium of
      mice. In the atria as well as in the conduction system, Cx40 is the most
      frequently expressed. In line with the localization and the conduction properties
      of distinct homotypic gap junction channels, the Cx40 deficient mouse is suitable
      for analysis of atrial arrhythmias. Cx40-deficiency in the mouse heart results in
      characteristic ECG changes like first degree atrioventricular block and
      prolongation of the QRS duration. Thus, an impairment of the sinuatrial,
      intraatrial and atrioventricular conduction properties is documented in Cx40
      deficient mice. These observations are associated with an increased atrial
      vulnerability. The Cx40 deficient mouse provides a good example of the relevance
      of transgenic mouse models to clarify the mechanisms of arrhythmogenesis. The
      clinical impact of future transgenic mouse models depends on the cooperation of
      geneticists, basic researchers and clinicians.

PMID- 11826833
TI  - [Granular media calcinosis of the aorta. Structural findings, historical review
      and pathogenetic significance].
AB  - Granular mediacalcinosis of the aorta seems to be a forgotten phenomenon that had
      been intensively investigated at the beginning of the past century. Without
      knowledge of this older literature we were, first of all, astonished to find in
      histological sections from aortic aneurysms, appearing "normal" in the H&E stain,
      severe calcifications of the media in von Kossa and Alizarin red S stained
      sections. Therefore, 24 operation specimens of aneurysms were investigated with
      several morphological methods. In all cases, light microscopy exhibited granular
      medial calcification with a slight increase of the severity in specimens from
      older patients. Scanning electron microscopy on paraffin sections revealed
      calcified globules with diameters of about 1 micron localized between the elastic
      laminae. By transmission electron microscopy these calcospherites occupied the
      space between the elastic laminae. X-ray microanalysis exhibited high amounts of
      calcium and phosphorus and a smaller amount of magnesium. This atomic composition
      supports the findings of Reid and Andersen (69) indicating that these
      calcifications are due to the deposition of whitlockite. These morphological
      findings are supplemented by a review of the older literature. The biological
      significance of this calcification remains unknown. On the one hand, it may be
      responsible for the increasing stiffness of the aorta in older age groups--and,
      on the other hand, a pathogenetic role for the development of dissecting
      aneurysms cannot be excluded. This may be supported by the effect of beta
      aminopropionitril in lathyric rats with destruction of the interlaminar fibers,
      described by Nakashima and Sueishi (65): it seems possible that a focal increased
      calcification in the human aorta may disturb the connection between the elastic
      laminae, thus, facilitating their separation.

PMID- 11826832
TI  - [2 year follow-up of 321 patients with an implantable cardioverter/defibrillator:
      comparison of patients with and without atrial fibrillation].
AB  - Atrial fibrillation is the most common cause of inappropriate therapy deliveries
      by implantable cardioverter/defibrillators (ICD). However, the importance of
      atrial fibrillation for the induction of ventricular arrhythmias and for the
      prognosis is controversial. We studied 321 ICD patients (pts) over the median
      follow-up of 25 months. In 92 pts, atrial fibrillation was found to be the
      underlying rhythm (in 49 pts chronic, in 43 pts paroxysmal), in 229 pts sinus
      rhythm. Pts with atrial fibrillation were older (67 +/- 9 vs. 63 +/- 9 years, p =
      0.001) and were considered to suffer more often from a valvular (14 vs. 4%, p =
      0.004) or a dilative cardiomyopathy (29 vs. 19%, p = 0.04). Both groups were
      similar regarding other baseline characteristics like gender, left ventricular
      ejection fraction, hypertension, diabetes and in the ICD system (single chamber,
      dual chamber) used. Pts with atrial fibrillation experienced more appropriate
      (ventricular fibrillation: 0.33 vs. 0.2/month, p = 0.0049, ventricular
      tachycardias: 0.05 vs 0/month, p = 0.0033) as well as inappropriate (34 vs. 8%, p
      < 0.001) therapy deliveries by the ICD. Pts with atrial fibrillation were found
      to suffer twice as much from a progression of their heart failure (43% vs. 22%, p
      < 0.001). After multivariate analysis, atrial fibrillation was significantly
      associated with progressive pump-failure mortality (relative risk (RR) 3.12,
      confidence interval (CI) 1.30 to 7.48, p = 0.01). There was no difference in the
      incidence of ICD therapies and mortality rates between the pts with chronic and
      paroxysmal atrial fibrillation. CONCLUSION: The presence of atrial fibrillation
      in ICD patients is associated with a progression of heart failure and therefore
      is an unfavorable factor for pump-failure death. Also, atrial fibrillation is a
      marker for greater possibility to experience more appropriate as well as
      inappropriate therapy deliveries by the ICD.

PMID- 11826835
TI  - [Modified endothelial cells in graft vasculopathy].
AB  - Occlusion of venous bypass grafts after coronary revascularization grafting
      represents the main reason for re-do operations. Arterial pressure as well as
      mechanical injury of the venous wall lead to endothelial dysfunction, causing
      intimal hyperplasia with luminal stenosis and eventually occlusion. In the
      transplanted heart, coronary artery disease limits the long-term success of
      cardiac transplantation. The disease is characterized by the interaction of
      activated immunologic cells and donor epicardical and microvascular endothelium.
      The ex vivo modification of endothelial cells may offer a therapeutic option to
      overcome both kinds of graft vasculopathy. Seeding of human endothelial cells on
      artificial and bioartificial acellularized vessel matrices has proven possible.
      The use of xenogenic matrices initially acellularized and recellularized with
      autologic endothelial cells and myofibroblasts may help to overcome the lack of
      vascular and valvular grafts with long durability. In addition, gene therapeutic
      methods to modify the function of such endothelial cells may offer a new
      therapeutic strategy, such as over-expression of nitric monoxide or inhibition of
      matrix metalloprotinases. First results of large animal studies show promising
      results and may lead to the first clinical trials in the near future.

PMID- 11826834
TI  - [MR angiography and flow measurement in coronary arteries and coronary bypass
      grafts].
AB  - Better MR image quality of coronary arteries and coronary grafts is the product
      of increased spatial and temporal resolution. Breathing artifacts could be
      reduced by implementing breath-holding and navigator techniques. With these
      developments normal coronary arteries can often be imaged reliably. Several
      trials have been performed in order to test the reliability of MR angiography to
      detect coronary artery stenosis. But up to now, sensitivity and specificity have
      proven to be too low to introduce these techniques in clinical routine. The
      patency of coronary grafts can be detected reliably using different MR
      techniques. Coronary flow reserve can be measured using the MR phase contrast
      technique. This noninvasive approach was tested in diseased coronary arteries and
      in graft stenoses. A reduced MR coronary flow reserve corresponded to reduced
      flow reserve measured invasively. Measurement of MR flow reserve in normal and
      diseased coronary grafts revealed significant differences (3.3 +/- 0.4 vs. 1.3 +/
      0.2).

PMID- 11826836
TI  - [Interaction of the coronary macro- and microcirculation].
AB  - In the following the impact of epicardial vessels on flow regulation in
      downstream resistive arteries and, vice versa, the potential influence of
      coronary microvascular disease on upstream conduit arteries will be reviewed.
      There is ample evidence that coronary artery disease of epicardial vessels leads
      to microvascular dysfunction not only due to a flow limiting stenoses with an
      altered regulation of vessel tone in the intra- and poststenotic segments, but
      also via distal microembolization of atherosclerotic material derived from
      upstream plaques. On the other hand, patients with hypertensive microvascular
      disease frequently reveal a disturbed endothelium-dependent and -independent
      regulation of epicardial vessel tone, although angiographic appearance is
      regular. Most strikingly, it could be demonstrated that in these patients with
      microvascular disease the incidence of coronary artery disease of epicardial
      vessels is increased several-fold as compared to age-matched populations. These
      findings suggest that hypertensive microvascular disease independent from the
      direct effect of hypertension on epicardial vessel affects upstream conduit
      arteries. Therefore a thorough and careful follow up of hypertensive patients
      with initially normal coronary arteriograms but preexistent microvascular disease
      appears advisable.

PMID- 11826837
TI  - [Effect of the imidazoline receptor agonist moxonidine on hemodynamics, coronary
      circulation, metabolic ischemia markers and the neurohumoral system in patients
      with essential hypertension. Effects of moxonidine on coronary circulation].
AB  - Moxonidine is a new centrally active imidazoline-receptor agonist being
      effectively applied in the treatment of arterial hypertension due to its
      sympathicolytic potency. This is the first investigation regarding the effects of
      moxonidine on coronary and systemic hemodynamics, metabolic markers of ischemia
      and neurohumoral parameters in patients with essential hypertension (WHO I-II).
      We studied moxonidine (single dose of 0.4 mg p.o.) in 22 patients with left
      ventricular (LV) hypertrophy, ST segment depressions during exercise, pectanginal
      complaints and negative coronarograms. Assessments included arterial blood
      pressure, cardiac output, pulmonary artery pressure mean (PAPm), pulmonary
      capillary wedge pressure (PCWP) and coronary sinus flow (CSF) by intravascular
      Doppler technique. The moxonidine-induced parameter changes 2 hours later were as
      follows: a decrease in systolic/diastolic pressure by 28/10 mmHg, and in heart
      rate by 5 bpm, associated with a decline of PAPm by 17% and of PCWP by 26%. LV
      work was reduced by 26%, MVO2 by 18% and CSF by 16%. Average peak velocity in CS
      fell by 18% and coronary flow reserve (with adenosine) increased by 12%. CS-O2
      saturation rose by 4%, accompanied by an increase in lactate extraction by 17%, a
      decrease in norepinephrine spillover by 30% and in arterial endotheline by 20%.
      In conclusion, moxonidine produces clinically relevant sympathicolysis with
      beneficial effects on hemodynamics, coronary circulation and neurohumoral
      parameters.

PMID- 11826838
TI  - Balance and imbalance of regional myocardial contractile function and blood flow.
AB  - During normoperfusion, both contractile function and myocardial blood flow are
      heterogeneously distributed throughout the left ventricle. Midwall segment
      shortening is greater at the apex than at the base of the left ventricle, and it
      is greater in the anterior than in the posterior wall. Also, transmural
      heterogeneity of myocardial deformation exists, with greater segment shortening
      and wall thickening in inner than in outer myocardial layers. Myocardial blood
      flow is greater in inner than in outer myocardial layers. Apart from transmural
      heterogeneities, there are adjacent regions with largely different resting flow
      in the same heart. While an increase in myocardial contractile function will lead
      to a metabolically mediated increase in myocardial blood flow, an increase in
      regional coronary perfusion within or above the autoregulatory range does not, in
      turn, increase regional myocardial contractile function. During hypoperfusion
      induced by a proximal coronary stenosis, the reduction in subendocardial blood
      flow is more pronounced than that in subepicardial blood flow, and contractile
      function in the inner myocardial layers ceases more rapidly than that in outer
      myocardial layers. The reduced regional myocardial contractile function is
      closely matched to the reduced regional myocardial blood flow; however, such
      coupling between reduced flow and function is lost when ischemia is prolonged for
      several hours, i.e., function for a given flow is further reduced. Acute
      embolization of the coronary microcirculation induces a progressive loss of
      regional myocardial function at unchanged regional myocardial blood flow, i.e.,
      perfusion-contraction mismatch. During reperfusion, regional myocardial
      contractile function remains depressed for a prolonged period of time, depending
      on the severity, duration and location of the preceding ischemic episode, while
      regional myocardial blood flow is restored.

PMID- 11826839
TI  - [Spatial heterogeneity of myocardial circulation and energy metabolism].
AB  - Within the left ventricular myocardium, substantial differences can be observed
      in terms of both perfusion and energy turnover. In addition to the small
      transmural gradient from the subepi--to the subendocardium (1:1.2), more recent
      high-resolution studies reveal a major patchwork-pattern, e.g., in terms of flow.
      Adjacent 200 microliters areas can differ more than 3-fold in local perfusion.
      Low flow and high flow areas (< 50% or > 150% of mean flow, respectively)
      represent up to 1/5 of the left ventricular myocardium. This local flow pattern
      is temporally stable for at least days and possibly weeks. Low and high flow
      areas also differ in local energy metabolism. High flow areas are characterized
      by enhanced glucose phosphorylation and fatty acid permeability, resulting in
      increased uptake of these substrates. This is the basis for the recent finding
      that high flow areas are characterized by an enhanced turnover of the citric acid
      cycle and thus of local O2 consumption. Since local O2 supply and consumption are
      closely coupled, low flow areas display no biochemical signs of ischemia.
      Reducing local flow by 50% results in a similar rise of adenosine or lactate in
      low and high flow areas. Following complete cessation of perfusion, high flow
      areas display a greater risk of infarction, indicating enhanced energy demand.
      Further studies are needed to elucidate the molecular basis of this spatial
      heterogeneity and to test whether the 3-fold differences in local energy turnover
      within the myocardial wall also translate into comparable variations of local
      contractility.

PMID- 11826840
TI  - ["Scientometry". Measure and number in science and economics].

PMID- 11826841
TI  - [Should we modernize the health system?].

PMID- 11826842
TI  - [A home nutritional rehabilitation trial for severly malnourished children].
AB  - A nutritional rehabilitation trial for severely malnourished children aged 6 to
      36 months (weight/height index using Z-score of less than -3 as the reference
      mean) was conducted in the poor suburban areas of Dakar, Senegal. Its purpose was
      to determine the effectiveness of a rehabilitation programme delivered in the
      home as compared to one provided in a nutritional recovery center (CREN). Ninety
      seven children benefited from rehabilitation at home and 51 at the CREN. At the
      end of two months of rehabilitation and after five months of charting their
      weight, the average weight gain was better in the group followed at home, but it
      still remained well under the 50 g/day recommended by WHO. Within the two groups,
      all of the children stayed underweight, with an average weight/height index Z
      score of less than -2.5 in the group followed at home, and a Z-score of less than
      -2.9 in the other group. The dropouts and the death rates in the two groups were
      comparable. The presence and availability of the mother as well as health
      education sessions adapted to each specific case through interpersonal
      communication seem to be the elements favouring the most effective rehabilitation
      being in the home.

PMID- 11826843
TI  - [The community pharmacist and the problem of excessive drinkers].
AB  - On a daily basis, the community pharmacist is just as concerned with alcohol
      (when detecting the interactions between alcohol and medication, or the use of
      alcohol as an excipient or active ingredient), as with alcoholism (when filling
      prescriptions, providing advice and guidance to patients, or undertaking other
      health education actions). In order to define the pharmacist's perception of the
      problem of alcoholism, an opinion poll was conducted by direct interrogation
      using a standardised questionnaire. The poll surveyed the owners of 101 randomly
      selected pharmacies in Puy de Dome. All of the pharmacists questioned are
      sensitive to and aware of the problem of interactions resulting from mixing
      alcohol and medication at the time of filling prescriptions. On the other hand,
      their perception of alcoholism and their behavior towards alcoholic patients
      vary. They frequently stressed the difficulty of establishing a dialogue. In
      spite of receiving information and training on alcoholism, perceived as
      insufficient, pharmacists claim to be really concerned by this problem. As field
      workers, community pharmacists think that they have a major role to play in
      carrying out health education campaigns and alcoholism prevention. In fact, the
      pharmacy is a privileged setting for facilitating encounters and discussions,
      where alcoholism, like all public health problems, can be addressed.

PMID- 11826844
TI  - [Non-compliance in HIV-infected patients, supported by a community association].
AB  - OBJECTIVE: To identify the factors linked to non-adherence to antiretroviral
      therapy in HIV-infected patients among the readership of REMAIDES, the AIDES
      association's medical information journal; AIDES is the principal organisation
      involved in the fight against AIDS in France. METHOD: A cross-cutting survey by
      questionnaire targeting the readers of REMAIDES. People who answered at least two
      independent questions as never forgetting or suspending their treatment were
      considered as adherents. RESULTS: Among the 1556 patients having responded to the
      survey, 888 (57%) are classified as adherents. The factors associated with non
      adherence are as follows: young age, minimal financial resources, alcohol
      consumption, a lack of perceiving the treatment's effectiveness, absence of
      impact on anticipation of the future or emotional life, difficulties as far as in
      keeping up the medications or the treatment's integration into daily life, the
      impossibility of stopping the treatment, a duration of treatment > 2 years,
      hepatitis C co-infection and problematic side effects. Non-adherence is explained
      by the negative real-life experience of the person throughout the treatment.
      Interventions which aim to accompany patients under multiple therapies are
      preferable in order to improve adherence and increase the probability of
      successful treatment.

PMID- 11826845
TI  - [A French tool for evaluation of home palliative care: adaptation of the Support
      Team Assessment Schedule].
AB  - The authors describe the utilisation of a quality assessment tool for palliative
      care administered at home. The questionnaire entitled Support Team Assessment
      Schedule (STAS) was translated from English for this study. It was then utilised
      comparatively with different quality of life evaluation instruments. Only the
      results of the STAS are described here. The approach allows for the unresolved
      problems in the care to come to the surface week after week. The STAS comprises
      nine items pertaining to the patient and his/her family, and seven items
      concerning the services provided. The study exhibits the results of 107
      evaluations completed from 50 patients stricken with cancer or AIDS in an
      advanced phase. The availability of this auto clinical audit tool, employable at
      home or in a hospital, constitutes an essential initial step in the field of
      French-speaking clinical evaluation of palliative care.

PMID- 11826846
TI  - [Preliminary validation of a poster on oral hygiene in the elderly].
AB  - This study calls attention to the preliminary validation of an educational poster
      on oral hygiene intended for people at least 65 years old living in a group home
      or benefiting from home care. The poster aims to modify certain risk behaviours.
      Twenty-four people from a middle class background participated in the study and
      were recruited from a day centre for the elderly of the Montreal region (Quebec,
      Canada). This study was carried out in three steps: the conceptualisation of the
      poster and two pre-tests. Interviews and the "focus group" method were both
      utilised for the collection of pertinent data. The two pre-tests indicated that
      the poster was easy to read, attractive and promoted the development of new
      skills in older people and the putting into practice of the conveyed messages.

PMID- 11826847
TI  - [Health education: a public service, a stake for modernization of the health
      system. Proposition for the health education committees].

PMID- 11826848
TI  - [The human sciences, victims of triple therapy].

PMID- 11826850
TI  - Endothelial cells and radiation gastrointestinal syndrome.

PMID- 11826849
TI  - [Meanwhile, the sociologists are working].

PMID- 11826851
TI  - Perinatally acquired HIV-2 infection diagnosed at 15 and 24 years of age.

PMID- 11826852
TI  - Chronic SIV infection ultimately causes immunodeficiency in African non-human
      primates.

PMID- 11826853
TI  - JAMA patient page. Low birth weight.

PMID- 11826854
TI  - [Standard for the selection of sputum from patients with anaerobic bacterial
      infections].

PMID- 11826855
TI  - [Points of view on microbial sensitivity tests].

PMID- 11826856
TI  - [Points of view on molecular detection and identification of anaerobic bacteria].

PMID- 11826857
TI  - [Factors that interfere with the progress of tests for the detection and
      isolation of anaerobic bacteria].

PMID- 11826858
TI  - This time, it's donors to the rescue.

PMID- 11826859
TI  - Platelet glycoprotein IIb/IIIa inhibitor effect examined in 2 studies.

PMID- 11826860
TI  - Is quantitation necessary for oncological PET studies? Against.

PMID- 11826862
TI  - An investigation of the roles of surface aluminum and acid sites in the zeolite
      MCM-22.
AB  - Ammonia adsorption studies reveal that the observed Lewis acidity in the zeolite
      MCM-22 is derived from at least two types of framework aluminum sites (AlF), that
      is, octahedral AlF and three-coordinate AlF. Comparative ammonia or
      trimethylphosphine (TMP) adsorption experiments with MCM-22 confirm that
      octahedral Al species gives rise to the signal at delta(iso) approximately 0 in
      the 27Al NMR spectrum; this is a superposition of two NMR signals from the
      different Al species on the water-reconstructed zeolite surface. A sharp
      resonance assigned to framework Al reversibly transforms on ammonia adsorption to
      delta(iso)27Al approximately 55 from tetrahedral AlF, while the broad peak is
      assigned to nonframework aluminum which results from hydrothermal treatment. This
      study also demonstrates the effectiveness of 27Al magic angle spinning (MAS) and
      multiple quantum (MQ) MAS NMR spectroscopy as a technique for the study of
      zeolite reactions.

PMID- 11826861
TI  - Synthesis of fragments of the glycocalyx glycan of the parasite Schistosoma
      mansoni.
AB  - The chemical synthesis of alpha-L-Fucp-(1 --> 3)-beta-D-GalpNAc-(1 --> 4)-beta-D
      GlcpNAc-(1 --> 3)-alpha-D-GalpO(CH2)5NH2, beta-D-GalpNAc-(1 --> 4)-[alpha-L-Fucp
      (1 --> 3)-]beta-D-GlcpNAc-(1 --> 3)-alpha-D-GalpO(CH2)5NH2, and alpha-L-Fucp-(1 -
      > 3)-beta-D-GalpNAc-(1 --> 4)-[alpha-L-Fucp-(1 --> 3)-]beta-D-GlcpNAc-(1 --> 3)
      alpha-D-GalpO(CH2)5NH2 is described. These structures represent fucosylated
      oligosaccharide fragments of the glycocalyx glycan of the cercarial stage of the
      parasite Schistosoma mansoni, and in protein-conjugated form they are potential
      diagnostics in the search for antibodies raised against the glycan in the serum
      of infected humans.

PMID- 11826863
TI  - Magnetic anisotropy of the antiferromagnetic ring [Cr8F8Piv16].
AB  - A new tetragonal (P42(1)2) crystalline form of [Cr8F8Piv16] (HPiv = pivalic acid,
      trimethyl acetic acid) is reported. The ring-shaped molecules, which are aligned
      in a parallel fashion in the unit cell, form almost perfectly planar, regular
      octagons. The interaction between the CrIII ions is antiferromagnetic (J = 12 cm(
      1)) which results in a S = 0 spin ground state. The low-lying spin excited states
      were investigated by cantilever torque magnetometry (CTM) and high-frequency EPR
      (HFEPR). The compound shows hard-axis anisotropy. The axial zero-field splitting
      (ZFS) parameters of the first two spin excited states (S = 1 and S = 2,
      respectively) are D1 = 1.59(3) cm(-1) or 1.63 cm(-1) (from CTM and HFEPR,
      respectively) and D2 = 0.37 cm(-1) (from HFEPR). The dipolar contributions to the
      ZFS of the S = 1 and S = 2 spin states were calculated with the point dipolar
      approximation. These contributions proved to be less than the combined single-ion
      contributions. Angular overlap model calculations that used parameters obtained
      from the electronic absorption spectrum, showed that the unique axis of the
      single-ion ZFS is at an angle of 19.3(1) degrees with respect to the ring axis.
      The excellent agreement between the experimental and the theoretical results show
      the validity of the used methods for the analysis of the magnetic anisotropy in
      antiferromagnetic CrIII rings.

PMID- 11826864
TI  - Size-dependent chemistry: properties of nanocrystals.
AB  - Properties of materials determined by their size are indeed fascinating and form
      the basis of the emerging area of nanoscience. In this article, we examine the
      size dependent electronic structure and properties of nanocrystals of
      semiconductors and metals to illustrate this aspect. We then discuss the chemical
      reactivity of metal nanocrystals which is strongly dependent on the size not only
      because of the large surface area but also a result of the significantly
      different electronic structure of the small nanocrystals. Nanoscale catalysis of
      gold exemplifies this feature. Size also plays a role in the assembly of
      nanocrystals into crystalline arrays. While we owe the beginnings of size
      dependent chemistry to the early studies of colloids, recent findings have added
      a new dimension to the subject.

PMID- 11826865
TI  - Metal-template-directed synthesis of diphosphorus compounds through
      intramolecular phosphinidene additions.
AB  - Heating the nonchelating cis-bis-7-phosphanorbornadiene-[Mo(CO)4] complex (13)
      results in the thermal decomposition of one of the 7-phosphanorbornadiene groups.
      The phosphinidene thus generated adds intramolecularly to a C=C bond of the other
      ligand to give the novel diphosphorus complex 14. This reaction constitutes a
      metal-template-directed synthesis. Likewise, the intramolecular phosphinidene
      addition to the C=C bond of a Mo-phospholene ligand affords the diphos complex
      18. Its crystal structure exhibits an extremely small P-Mo-P bite-angle for a
      five-membered chelate ring. The similar intramolecular 1,2-addition to a C=C bond
      of a phosphole ligand gives a highly strained, unstable intermediate product.
      Scission of its P-Mo bond generates a free coordination site, which is then
      occupied by either CO or a phosphole to yield complexes 22 and 23, respectively.
      The analogous intermolecular addition of [PhPW(CO)5] to a [phosphole-W(CO)5]
      complex gives the di-[W(CO)5] complexed adduct 28. The directing effect of the
      metal on the intra- and intermolecular additions is discussed.

PMID- 11826866
TI  - Zirconocene-mediated, high-yielding macrocyclizations of silyl-terminated diynes.
AB  - A series of silyl-terminated diynes of varying lengths and substitution patterns
      have been prepared. These diynes undergo zirconocene coupling with selective
      formation of trimeric macrocycles from linear alkynes, while nonlinear diynes
      give cyclodimeric products. The length of the linear diynes can be increased for
      the preparation of macrocycles with large nanoscale cavities. Reaction of the
      zirconium-containing macrocycles with acid results in the synthesis of metal-free
      cyclophanes. All of these macrocycles were prepared in multigram quantities, in
      the absence of high-dilution conditions, to give products in > 75% yield that are
      easily purified as crystalline solids.

PMID- 11826867
TI  - Urinary excretion of pyridinium crosslinks in short children treated with growth
      hormone.
AB  - The aim of this study was to evaluate the effect of growth hormone (GH) treatment
      on bone resorption in children with GH deficiency and those with idiopathic short
      stature. The study population included seven children with subnormal spontaneous
      GH secretion and 13 children with idiopathic short stature, all of them pre
      pubertal. Anthropometric measurements, free, protein-bound and total urinary
      pyridinoline (Pyd) and deoxypyridinoline (Dpd), serum GH, and serum
      immunoreactive PTH were measured at baseline and months 1, 3, 6 and 12 of GH
      treatment. The urinary excretion of total Pyd and Dpd, standardized by the cube
      of height (m3) in overnight, 24-hour urine collections was not different from age
      matched healthy controls at baseline in either group of patients. During
      treatment with human recombinant GH, both pyridinium crosslinks increased above
      normal values, reaching a peak after one month in children with GH deficiency and
      later (after 3-6 months) in children with short stature. Free and total crosslink
      forms were correlated, and GH treatment did not affect the proportion of free to
      bound crosslinks. Serum concentrations of iPTH showed a moderate but not
      statistically significant increase. This study provides no evidence of reduced
      bone resorption in untreated GH deficiency or in idiopathic short stature. GH
      treatment induced a marked, but temporary, increase of bone resorption in both
      groups of patients.

PMID- 11826868
TI  - The relationship between ovarian structure and serum insulin, insulin-like growth
      factor-I (IGF-I) and its binding protein (IGFBP-1 and IGFBP-3) levels in
      premature pubarche.
AB  - The aim of this study was to determine serum insulin, insulin-like growth factor
      I (IGF-I) and its binding proteins (IGFBP-1 and IGFBP-3) levels and their
      relationship with androgen levels and ovarian structure in 23 girls with
      premature pubarche (PP). Fasting levels of testosterone, dehydroepiandrosterone
      (DHEA) and its sulfate (DHEAS), androstenedione (delta4A), sex hormone binding
      globulin (SHBG), glucose (G), insulin (I), IGF-I, IGFBP-1, IGFBP-3 were measured.
      Androgens or steroid hormone levels > 3 SD of normal postpubertal levels were
      considered as an exaggerated response to the ACTH test. The fasting I to G ratio
      (FIGR) was calculated and FIGR > 22 was suggestive of insulin resistance (IR). A
      pelvic ultrasound (US) was carried out and the ovarian structure was divided into
      five classes (c): c1--homogeneous, c2--microcystic, c3--multicystic, c4-
      polycystic and c5--follicular. The girls with PP were divided into two groups
      according to the main ovarian classes observed: PPc1 (n = 6) and PPc2 (n = 15).
      The FIGR showed IR in 44% of patients. The androgens, SHBG, G, I, FIGR, IGF-I and
      IGFBP-1 levels were similar among the groups (PPc1 vs PPc2). An exaggerated
      response to ACTH was more common and IGFBP-3 levels were higher in the PPc2 than
      in the PPc1 group (p = 0.04). Regression analysis revealed that I was correlated
      with DHEAS (r = -0.43, p = 0.04) and IGFBP-1 (r = -0.51, p = 0.01); IGF-I was
      correlated with DHEA (r = -0.42, p = 0.05), delta4A (r = -0.47, p = 0.02), SHBG
      (r = -0.43, p = 0.04), IGFBP-1 (r = -0.61, p = 0.002) and IGFBP-3 (r = 0.56, p =
      0.005); IGFBP-1 was correlated with SHBG (r = 0.56, p = 0.005). These findings
      suggest that there might be interactions between the insulin-IGF-I-IGFBPs system
      and hyperandrogenism. However, the possible causal role of adrenal androgen
      hypersecretion on the insulin-IGF-I-IGFBPs axis and ovarian structure in girls
      with PP remains to be established. Since studies reveal that IGFBP-3 levels could
      be a negative predictor for insulin sensitivity throughout puberty, we
      hypothesize that girls with PP and microcystic ovaries are at risk of developing
      IR in the course of normal puberty.

PMID- 11826869
TI  - Bone mineral density and body composition in Noonan's syndrome: effects of growth
      hormone treatment.
AB  - We assessed bone mineral density (BMD) and body composition in children with
      Noonan's syndrome (NS) before and during growth hormone (GH) treatment. Sixteen
      children (12 boys, 4 girls) with NS aged 5.8-14.2 (mean 10.0) years were studied
      for 2 years. Anthropometry, BMD measurements by radiographic absorptiometry and
      bioimpedance measurements (Akern-BIA 101/S) were performed at baseline and after
      3, 6, 12 and 24 months. Daily GH dosage was 0.05 mg/kg. Trabecular volumetric BMD
      was normal; cortical BMD was in the lower normal range at baseline and slightly
      increased over the 2 years. Fat free mass and total body water were below normal
      at the start and increased significantly over the first 3 months, with a slight
      increment thereafter. Percentage fat mass decreased over the first 6 months and
      increased thereafter. These findings are comparable to the data on body
      composition in short normal children and girls with Turner's syndrome treated
      with GH.

PMID- 11826870
TI  - Sarcocystis neurona reacting antibodies in Missouri feral domestic cats (Felis
      domesticus) and their role as an intermediate host.
AB  - Sarcocystis neurona is the parasite associated with equine protozoal
      myeloencephalitis (EPM). Recently, cats (Felis domesticus) have been implicated
      as a potential intermediate host in the life cycle of S. neurona. This study was
      initiated to determine whether cats have antibodies that react to S. neurona
      antigens similar to antibodies from horses with EPM, and to evaluate the role of
      cats as intermediate hosts in the parasite's life cycle. Nine feral cats were
      used for analysis. Only one had antibodies reacting to S. neurona antigens.
      Muscle tissue from this cat, with detectable sarcocysts in the tongue, was fed to
      an opossum (Didelphis virginiana). The opossum shed sporocysts, which were then
      fed to gamma-interferon receptor knockout mice. Histopathology,
      immunohistochemistry, parasite isolation and molecular analysis were used to
      examine the pathology and associated parasites in the mice. The study suggests
      that the domestic cat can serve as an intermediate host to S. neurona or a S.
      neurona-like organsim.

PMID- 11826872
TI  - Quantification of sulfur and sulfur-containing compounds in wastewaters by means
      of a combination of liquid chromatographic methods.
AB  - Low-micromolar concentrations of sulfite, thiosulfate and sulfide, present in
      synthetic wastewater or anaerobic digester effluent, were quantified by means of
      derivatization with monobromobimane, followed by HPLC separation with
      fluorescence detection. The concentration of elemental sulfur was determined,
      after its extraction with chloroform from the derivatized sample. by HPLC with UV
      detection. Recoveries of sulfide (both matrices), and of thiosulfate and sulfite
      (synthetic wastewater) were between 98 and 103%. The in-run RSDs on separate
      derivatizations were 13 and 19% for sulfite (two tests), between 1.5 and 6.6% for
      thiosulfate (two tests) and between 4.1 and 7.7% for sulfide (three tests).
      Response factors for derivatives of sulfide and thiosulfate, but not sulfite,
      were steady over a 13-month period during which 730 samples were analysed.
      Dithionate and tetrathionate did not seem to be detectable with this method. The
      distinctness of the elemental sulfur and the derivatizing-agent peaks was
      improved considerably by detecting elution at 297 instead of 263 nm.

PMID- 11826871
TI  - Some species of the genus Myxobolus (Myxozoa: Myxosporea) infecting freshwater
      fish of the River Nile, Egypt, and the impact on their hosts.
AB  - Six Myxobolus species are described from Nile fish, five of which are new and one
      is redescribed: M. naffari Abdel Ghaffar et al., 1998 was recovered from the
      gills of Labeo niloticus and the mouth of Barbus bynni; M. caudatus sp. n. was
      observed in the tail fin of B. bynni; M. fahmii sp. n. occurred in the gills of
      B. bynni; M. imami sp. n. was found in the kidney of L. niloticus; M.
      intestinalis sp. n. was recorded from the intestine of B. bynni; and M. perforata
      sp. n. was found in the internal surface of the operculum of Hydrocynus
      forskalii. The histological effects of some of the Myxobolus infections present
      are described.

PMID- 11826873
TI  - Contactless conductivity detection for capillary electrophoresis. Hardware
      improvements and optimization of the input-signal amplitude and frequency.
AB  - A new prototype of contactless conductivity detector, smaller and easier to
      operate than the former version, is described. For a fused-silica capillary with
      142-microm wall thickness and voltages up to 25 kV, it can be placed at the low-
      or high-voltage end of the column. This feature allowed implementation of an
      apparatus with sample introduction at the grounded end of the column. The input
      signal is an important parameter for determining the signal-to-noise ratio (S/N)
      of the detection system. An optimization procedure of its amplitude and frequency
      is proposed. Although the SIN must be determined by introduction of actual
      samples, the operating conditions can be optimized merely by changing the signal
      parameters and by using a mathematical procedure. Thus, an easy and fast
      optimization routine can be carried out. Mathematical and instrumental
      backgrounds are discussed, and experimental support of the technique's
      effectiveness is presented.

PMID- 11826874
TI  - The acquired midtarsus deformity classification system--interobserver reliability
      and intraobserver reproducibility.
AB  - A radiographic classification (Schon's) divides Charcot midtarsus deformities
      into four types identified by Roman numerals (I to IV), according to the
      anatomical location of the pathological process,11 and an objective method of
      severity staging using radiographic criteria is introduced and tested. A beta
      stage is assigned if one of the following criteria is met: 1. a dislocation is
      present; 2. the lateral talar-first metatarsal angle is > or = 30 degrees; 3. the
      lateral calcaneal-fifth metatarsal angle > or = 0; or 4. the AP talar-first
      metatarsal angle is > or = 35 degrees. An alpha stage can be assigned when all
      four features are absent. Clinical features useful in assessing and managing
      these deformities have been associated with the various types and stages. To
      determine whether the classification system is valid, a study was performed. Two
      examination booklets and an instructional booklet designed to teach the method
      were distributed to 75 orthopaedic surgeons at the AOFAS summer meeting to test
      for intraobserver reproducibility and interobserver reliability. Information
      about the participants was recorded, and the tests were scored. The highest
      scores for correct responses were achieved by foot and ankle fellows, followed by
      orthopaedic residents. Attending orthopaedic surgeons achieved the lowest scores.
      The most common error was a type I deformity misidentified as a type II. The
      interobserver reliability for correctly classifying the deformities was 81%, and
      the intraobserver reproducibility was 97%. We concluded that this classification
      system, intended to clarify the patterns of acquired midfoot collapse, permits
      assignment of both anatomic type (I to IV) and degree of severity (alpha-beta)
      with high reliability and reproducibility. It can therefore be used as a tool for
      diagnosis, planning treatment, and assessing the prognosis.

PMID- 11826875
TI  - The difficulty of height prediction in Weaver syndrome.
AB  - Accelerated growth and advanced bone age are consistent findings in Weaver-Smith
      syndrome (WSS). According to the rather scant reports in the literature, persons
      afflicted with WSS appear to achieve supranormal heights despite a significant
      bone age advancement in their growth period. The literature does not state
      clearly whether there is a discrepancy between bone age advancement and the time
      of onset of puberty in WSS. We report a girl with Weaver syndrome whose final
      height predictions were within normal limits according to the standard prediction
      models, who had to be eventually treated with high doses of estrogen in order to
      keep her final height within reasonable limits. We conclude that the pattern of
      growth and maturation in children with WSS may form an exception to the general
      rule that tall children with an advanced bone age mature early and thus attain a
      normal final height. A careful evaluation of growth data of other children with
      WSS is necessary to clarify this issue.

PMID- 11826876
TI  - Intestinal mucosa on top of a rudimentary occipital meningocele in amniotic
      rupture sequence: disorganization-like syndrome, homeotic transformation,
      abnormal surface encounter or endoectodermal adhesion?
AB  - We present a case of a peculiar rudimentary occipital meningocele that was
      surgically removed when the patient (a boy) was 5 months of age. The patient also
      had distal transverse defects of both hands. The association of congenital scalp
      defects and distal congenital hand anomalies is relatively rare and one form is
      known as the Adams-Oliver syndrome. To our surprise, microscopic examination
      revealed intestinal mucosa on top of the skin tag containing the rudimentary
      meningocele. No comparable cases were found in the literature. We discuss the
      following possible explanations for this peculiar situation: 1) disorganization
      like syndrome; 2) homeotic transformation; 3) abnormal surface encounter between
      the epidermis and remnants of the yolk sac or omphalo-enteric duct; and 4)
      endoectodermal adhesion in the presomite embryo.

PMID- 11826877
TI  - Growth status of children 6-12 years from two different geographic regions of
      Mexico.
AB  - PRIMARY OBJECTIVES: The purposes of the study are to assess the growth status of
      urban Mexican children living in different geographic areas of the country, to
      estimate the prevalence of overweight and obesity, and to explore secular trends
      in body size. DESIGN: Cross-sectional surveys of 293 children 6-11 years from
      Sonora in the north-west of the country (155 boys, 138 girls), and 356 children 7
      12 years from Veracruz on the Gulf Coast (194 boys, 162 girls) were undertaken in
      1992 and 1993, respectively. PROCEDURES: Height and weight were measured; the
      body mass index (BMI, kg m(-2)) was calculated. Growth status was compared to USA
      reference data and to samples of Mexican children in 1926 and 1975. The
      prevalence of overweight (BMI > or = 85th and < 95th percentiles) and obesity
      (BMI > or = 95th percentile) was estimated. RESULTS: Girls and boys from Sonora
      and Veracruz do not differ in height, weight and the BMI. Mean heights are at
      (girls) or below (boys) the medians of USA growth charts, while mean weights are
      at (boys) or just below (girls) the 75th percentiles at most ages. As a result,
      mean BMIs are above (boys) and below (girls) the 75th percentiles over the age
      range studied. The prevalence of overweight and obesity is 40% in boys and 35% in
      girls, whereas the prevalence of obesity per se is 23% in boys and 17% in girls.
      Compared to urban Mexican children in the Federal District surveyed in 1926,
      children in the present sample are taller and heavier, but the secular trend in
      body weight is more pronounced since the mid-1960s. Heights of the current
      samples are similar to those of well-off children in Mexico City in the early
      1970s, but weights are heavier. CONCLUSIONS: The gap in height between well-off
      and lower socioeconomic status children in different regions of Mexico has been
      reduced, but there is an increase in the prevalence of overweight and obesity.

PMID- 11826878
TI  - Stability of somatotypes in 4 to 10 year-old rural South African girls.
AB  - In 1996, a mixed Ellisras longitudinal study (ELS) was initiated to assess the
      stability of somatotypes in 408 girls who comprised 99 pre-school and 309 primary
      school children in Ellisras rural area in the Northern Province of South Africa.
      The children's somatotype was assessed using the Heath-Carter anthropometric
      method. Anthropometric dimensions were taken according to the protocol of the
      International Society for the Advancement of Kinanthropometry (ISAK). The most
      stable pre-school and primary school girl had migratory distances (MDs) of 2.6
      and 3.4, respectively, while the least stable pre-school and primary school girl
      had MDs of 17.9 and 24.4, respectively. The mean somatotype of the pre-school
      children was mesomorph-ectomorph throughout the complete age range, while the
      mean somatotype of primary school girls was mesomorph-ectomorph for all the age
      groups except for the 9.5 years group at which it was in the balanced ectomorph.
      The inter-age partial correlations for endomorphy and ectomorphy were high and
      significant, but insignificant with regard to mesomorphy.

PMID- 11826879
TI  - Longitudinal changes in isokinetic leg strength in 10-14-year-olds.
AB  - This study used multilevel regression modelling to longitudinally investigate the
      influences of age, sex, body size, skinfold thicknesses and maturity on the
      development of isokinetic knee extension and flexion on eight occasions over a 4
      year period. Forty-one subjects (20 boys and 21 girls) were measured and 295
      isokinetic leg strength tests and associated measures were successfully
      completed. Subjects were aged 10.0 +/- 0.3 years at the onset of the study.
      Stature, body mass, triceps and subscapular skinfold thicknesses, and sexual
      maturation (according to pubic hair development) were assessed at each test
      occasion. Isokinetic concentric knee extension and flexion of the dominant leg
      were determined to elicit maximal peak extension (PET) and flexion torque (PFT).
      Statistical significance was accepted at p < 0.05. Multilevel regression
      modelling indicated that stature and mass were significant predictors of both PET
      and PFT. Age and maturity were non-significant explanatory variables once stature
      and mass had been accounted for. Skinfold thickness exerted a significant
      negative effect independent of mass and stature on PFT but not PET. At test
      occasion 8, cross-sectional areas (CSAs) of the knee extensors (ExCSA) and
      flexors (FlexCSA) were determined using magnetic resonance imaging on 23 boys and
      14 girls and examined as predictors of isokinetic leg strength. There were no
      significant sex-related differences in PET or PFT. Pearson product moment
      correlation coefficients indicated a significant relationship between ExCSA and
      PET and FlexCSA and PFT for both boys and girls. Analysis of covariance (ANCOVA)
      demonstrated that ExCSA and FlexCSA were significant explanatory variables for
      PET and PFT, respectively, but became non-significant once stature and mass had
      been introduced into the analysis. To conclude, there were no significant sex
      differences in PET or PFT between the ages of 10 and 14 years and the development
      of PET and PFT could be accounted for by the increase in stature and mass. Age,
      maturity and thigh muscle CSA were all non-explanatory variables in the
      production of PET and PFT once body size had been controlled for.

PMID- 11826880
TI  - Family themes of food refusal: disciplining the body and punishing the family.
AB  - A problematic issue in studying anorexia nervosa (AN) has been the absence of a
      qualitative study that probes the deep meanings of food refusal. We attempt to
      close this gap by studying the family meanings of food refusal by a single case
      study of a family in Hong Kong with an AN daughter. Eight videotapes of family
      therapy sessions, each lasting 90 minutes, were intensively reviewed, transcribed
      verbatim, and content analyzed. Two family themes of food refusal were discerned:
      the AN daughter disciplined her body and punished her family. The conclusions
      imply a need to revisit the Chinese gender role expectation in understanding AN
      patients and their families.

PMID- 11826881
TI  - Plasma exogenous creatinine clearance test in dogs: comparison with other methods
      and proposed limited sampling strategy.
AB  - Plasma clearance of creatinine was evaluated for assessment of glomerular
      filtration rate (GFR) in dogs. In 6 healthy dogs (Experiment 1), we determined 24
      hour urine clearance of endogenous creatinine, plasma, and urine clearances of
      exogenous creatinine administered at 40, 80, and 160 mg/kg in a crossover design
      (linearity study), plasma iothalamate clearance, and plasma and urine clearances
      of 14C-inulin. In Experiment 2, plasma creatinine and iothalamate clearances were
      compared, and a linearity study was performed as for Experiment 1 in 6 dogs with
      surgically induced renal impairment. Experiment 3 compared plasma creatinine
      clearance with plasma iothalamate clearance before and 3 weeks after induction of
      moderate renal impairment in 6 dogs. Plasma creatinine clearances were calculated
      by both noncompartmental and compartmental analyses. In Experiment 1, plasma
      inulin clearance was higher (P < .001) than other clearance values. Plasma
      creatinine clearances at the 3 dose rates did not differ from urine inulin
      clearance and each other. In Experiment 2, plasma creatinine clearances were
      about 14% lower than plasma iothalamate clearance (P < .05). In Experiment 3,
      decreases in GFR assessed by plasma clearances of iothalamate and creatinine were
      similar. Renal failure decreased the daily endogenous input rate of creatinine by
      25%. Limiting sampling strategies for optimizing GFR calculation were proposed,
      allowing an error lower than 6.5% with 4 blood samples. These results suggest
      that determination of plasma creatinine clearance by a noncompartmental approach
      offers a reliable, inexpensive, rapid, and convenient means of estimating GFR in
      routine practice.

PMID- 11826882
TI  - Stable circadian rhythms as a property of cell populations.
AB  - Our paper analyzes the main difficulties which the theory of circadian rhythms
      encounters in an attempt to explain the mechanisms of biological clocks. It is
      shown that the assumption of a small concentration of the enzymes involved in the
      cell-clock mechanism allows explaining such well-known properties of biological
      clocks as: 1) a large period of the circadian oscillation; 2) insignificant
      energy consumption; 3) insensitivity to inhibitors; 4) temperature independence;
      5) initiation of circadian oscillations in response to a short single external
      impulse; 6) a limited possibility of synchronization by periodic external
      factors. It is shown also that the self-oscillating clock mechanism may exist at
      the level of cell populations. This mechanism is considered to be a temperature
      dependent component of the circadian clocks in multicellular organisms.

PMID- 11826883
TI  - The effects of electric fields on circadian rhythmicity in men.
AB  - In an underground bunker built for the study of human circadian rhythms, one of
      the two experimental rooms is shielded against natural magnetic and electric
      fields. So far, autonomous rhythms of 82 subjects have been measured. As a
      result, the mean period value is lower in the non-shielded room than in the
      shielded room (significant with p< 0.01). Moreover, real internal
      desynchronization has been observed only in the shielded room (p = 0.0001); in
      opposition to this, apparent desynchronization with circa-bi-dian activity
      periods has been observed only in the non-shielded room (p = 0.01). This means
      that the total of the natural electromagnetic fields shortens the circadian
      period, and it strengthens the interaction between activity rhythm and the
      vegetative rhythms. Artificial constant fields, electric and magnetic, do not
      influence human circadian rhythms. However, a weak electric field, alternating
      with a frequency of 10 Hz, affects human circadian rhythms in the same manner as
      the total of the natural fields; i.e., it shortens the period (p< 0.001), and it
      prevents real internal desynchronization (p< 0.02). With this control of human
      circadian rhythms by a stimulus not perceptible consciously, a model for
      circadian rhythms derived from animal experiments can be confirmed in human
      experiments. On the other hand, with circadian rhythms as an indicator, natural
      electromagnetic fields are proved to be effective on human beings for the first
      time; this may be of interest with regard to space where these fields are absent.

PMID- 11826884
TI  - Frequency spectra and cosinor for evaluating circadian rhythms in rodent data and
      in man during Gemini and Vostok flights.
AB  - With the advent of a capability for extraterrestrial existence of lifeforms,
      chronobiology--the study of biological rhythms--has reached a position analogous
      to that of classical endocrinology. Just as an endocrine gland can be removed
      from an experimental animal, the effects of removal examined and the gland (or an
      extract) then replaced to determine whether the removal effects are reversible,
      lifeforms should be rigorously evaluated by rhythmometry before and during their
      (attempted) removal from Earth effects, as well as following their return to
      Earth. Methods lending themselves to such studies before, during and after travel
      in extraterrestrial space are illustrated herein, and their applications may be
      of value to preventive medicine as well as to basic science. Analyses of
      terrestrial control data and of restricted time series from extraterrestrial
      missions indicate that substantial scientific returns on Earth can be anticipated
      if in the routine of all mammalian space travelers provisions are made for: (1)
      monitoring body core temperature so as to evaluate its stable circadian rhythm--a
      phenomenon of interest in itself and also a reference rhythm for other variables;
      (2) saving aliquots from all urine samples, whereby a spectrum of diverse rhythms
      can be examined; (3) repeating simple performance tests, e.g., of grip strength
      or eye-hand coordination. Plans also should be implemented in unmanned space
      vehicles for explicit chronobiologic studies so designed that daily cosinor
      analysis can determine, e.g., whether circadian phase control or the
      desynchronized period length be altered as we move away from the Earth. Thus,
      some of the mechanisms underlying rhythms are now amenable to study on
      experimental mammals in unmanned space vehicles. In view of the high degree of
      generality of mammalian rhythms--many related to human well-being and optimal
      performance--and of dramatic consequences from some rhythmic variations in man,
      such studies deserve time and attention equal to that expended on weather and
      communication satellites.

PMID- 11826885
TI  - Diurnal rhythm of the pituitary-adrenocortical response to stress: effect of
      constant light and constant darkness.
AB  - The existence of a biological rhythm in the response of animals to noxious
      stimuli and drugs is well known. However, the mechanism of this response is not
      well understood. This study was undertaken to describe the existence of a diurnal
      rhythm in the hypothalamic-pituitary-adrenocortical system before and after
      stress in female rats kept in controlled environmental conditions in 12L:12D,
      24L:OD, or OL:24D. Plasma ACTH and plasma corticosterone concentrations were
      compared in unstressed animals. The time pattern in the response to stress was
      determined at four hourly intervals during a 24 hr period in which plasma ACTH
      and plasma corticosterone were measured at different time intervals. The stress
      response varied considerably with time of day in both magnitude and duration. The
      adrenals of rats exposed to constant light for 45 days atrophied, whereas the
      adrenals of animals kept in constant dark for the same period did not differ
      significantly from those of controls kept in 12L:12D. The increase in plasma ACTH
      in response to stress was greater both in the animals maintained in constant
      light and in constant dark than in the 12L:12D controls. Homeostatic mechanisms
      involved in these changes are discussed.

PMID- 11826886
TI  - Mechanisms of action of light on circadian rhythms in the monkey.
AB  - Light is considered by many investigators to be the primary Zeitgeber for most
      physiologic rhythms. In order to study the effects on biorhythms of changing
      photoperiods and to provide information on the nature of the wave forms and the
      mechanisms of entrainment, unrestrained male monkeys (Cebus albifrons, Macaca
      nemestrina) were maintained in a sound-proofed environmental chamber. The Cebus
      was initially maintained on a 12L:12D schedule; it was subjected to a 180 degrees
      phase shift for 14 days, then returned to the original photoperiod. In two
      experiments (24 days; 27 days each) the same monkey was again maintained on a
      12L:12D schedule which was gradually altered to a constant light environment.
      Deep body temperature (DBT) data were obtained with miniature radiotransmitters.
      Locomotor activity (LMA) was measured by strain gauges. Under the 12L:12D
      regimens the Macaca DBT cycles were uniform as to phase and wave form for over 60
      weeks. These wave forms were analyzed by the use of periodogram and correlogram
      analyses and by fitting to the Volterra Integro-Differential Equation. Phase
      angle relationships between Zeitgeber and physiologic parameters were
      characterized. After the photoperiod phase shift the DBT cycle rephased in about
      9 days. During the rephasing process the wave form changed. The shapes of the
      wave forms of DBT and activity were maintained with increasing light until an
      18L:6D photoperiod was reached. The rhythms were entrained to the onset of
      darkness rather than lights on. Major and minor periods of LMA were detected.
      Hysteresis diagrams showed that DBT led the onset of major LA by 6 hr and the end
      of major activity by 2 hr.

PMID- 11826887
TI  - An effect of weightlessness following exposure to vibration.
AB  - Vibration of germinating wheat seedlings at the levels experienced during the
      launch of the NASA Biosatellite II increases the frequency of developmental
      arrest in seedling organs. Severe vibrations lasted approximately 30 sec in two
      stages. Power spectral density was greatest at frequencies around 15-16 and 19-22
      Hz on the entire vehicle. Vibration forces reaching the affected parts of
      individual seedlings could not be measured. One or more seedling organs may be
      expected to be absent in 11% of selected Earth-grown wheat plants. If subjected
      to simulated launch vibration between 12 and 27 hr after the start of
      germination, the number of abnormal plants rises to 21.6%. Lateral roots are most
      affected by vibration at this age. Seedlings which went into orbital
      weightlessness aboard Biosatellite II, or were grown for several days on a
      horizontal clinostat after vibration, showed only 5.3% abnormalities. Simulated
      weightlessness on the clinostat without prior vibration did not alter the number
      of abnormal plants. It is suggested that growth in weightlessness following
      exposure to vibration permits more extensive repair of injury produced by
      vibration than does growth in Earth's gravity.

PMID- 11826888
TI  - Food technology problems related to space feeding.
AB  - The development of foods suitable for extraterrestrial consumption posed unique
      problems. Limitations on weight, volume and stability of space food together with
      the lack of refrigeration favored the use of dehydrated foods on Gemini and
      Apollo menus. Environmental constraints, cabin pressures of 1/3 atmosphere with
      exposure of the food assembly to the vacuum of space in conjunction with
      extravehicular activities and zero gravity required special packaging and
      adaptation of foods considered suitable for space flight use. Requirements for
      acceptable, familiar, crumb free, low residue, non-gas producing, stable foods
      added to the complexity of the developmental effort. Four basic approaches:
      semisolid foods in metal tubes, dehydrated bite-size foods to be eaten dry,
      dehydrated foods to be reconstituted before eating and flexibly packaged
      thermostabilized wet meat products have been utilized in the feeding systems
      developed for Projects Mercury, Gemini and Apollo. The development of each type
      posed many interesting technologic problems. Data from current Apollo flights
      have pointed to certain deficiencies which still remain to be corrected. Work is
      progressing to eliminate current problems and to provide feeding systems suitable
      for both short-term and long-term space flights.

PMID- 11826889
TI  - The proportions of carbohydrate, fat and protein in space feeding.
AB  - Most of the weight of food supply is due to the need for energy. Fat is most
      efficient because it has a higher ratio of carbon and hydrogen to oxygen than do
      protein and carbohydrate, so stored food systems for long missions would
      logically rely heavily on this form of calories. Biological systems proposed for
      atmosphere regeneration yield potentially edible products quite high in protein,
      whereas chemical systems provide carbohydrate as sugars and alcohols if they
      produce food at all. There is a minimum need for all three forms to fulfill
      essential nutrient functions besides energy. These minimal needs are reasonably
      well known, but only for short times in terrestrial environment. Lower limits,
      thought to be about 45 g protein, 7 g fat, and 70 g carbohydrate, may need to be
      increased somewhat in space due to altered oxygen concentration, hypokinesia and
      other stresses. Upper limitations are less clearly established, even for earth
      environment. High intakes of protein result in increased water requirement, loss
      of minerals (correction of minierals) and excessive urinary uric acid. Intestinal
      absorption and metabolic capacity for fat are known to be limited. Although
      carbohydrate is usually quite innocuous, some forms are not well tolerated in
      high concentration. Provisional allowance ranges are, in % of total calories: 8
      50 protein, 2-75 fat and 10-90 carbohydrate.

PMID- 11826891
TI  - Survival of microorganisms under simulated space conditions.
AB  - Monocellular layers of stationary phase cells of Escherichia coli B/r were
      exposed to high vacuum of 10(-6) Torr at different temperatures. After
      simultaneous irradiation with UV of 254 nm or X-rays, the survival was tested as
      colony forming ability. In vacuum the sensitivity to UV and X-rays was enhanced
      compared with the controls at atmospheric pressure. Of UV-inactivation in vacuum
      no photoreactivation was found.

PMID- 11826890
TI  - Calcium metabolism in space flight.
AB  - Immobilization has been shown repeatedly to induce a loss of skeletal substance
      accompanied by hypercalcemia and hypercalcuria. Older data from paraplegics,
      polio patients, fracture patients and immobilized normal volunteers are reviewed.
      More recent studies of bone densitometry on normal volunteers and astronauts of
      Gemini flights IV, V, and VII are reported briefly. Finally, metabolic balance
      studies from Gemini VII are summarized. The balance data suggest that adequate
      calcium intake and programmed exercise may control the problem of calcium
      mobilization. However, there are disquieting discrepancies between the
      densitometric results (which show bone losses) and the balance data (which show
      no bone loss). Either the densitometric results are in error or there occur
      alarming intraskeletal transfers of bone mineral not detected by the balance
      approach.

PMID- 11826892
TI  - Current status of French research on the biological effects of heavy ions in
      cosmic radiation as observed in high-altitude balloons.
AB  - On casual inspection, cosmic rays may not be considered to pose a biological
      hazard. Nevertheless, the heavy ion component does produce a significant but very
      local irradiation. This has been confirmed by the hair whitening in black-haired
      animals. Experiments with black C 57 mice in balloons at 30,000 m altitude show
      white-haired tufts along the tracks of heavy ions. Histological and
      radioautographic studies were carried out; the results are reported. Similar
      investigations on black rabbits gave similar results and confirm those obtained
      previously with black mice. In the discussion, we report that tissue damage is
      amplified. This fact is not yet explained, but suggests reconsideration of the
      calculation of radiation dosage. The ionization distribution induced by heavy
      ions is analyzed. We point out that along their tracks the dosage is very
      important; therefore it is necessary to investigate their biological action,
      particle by particle, according to their energy and their charge.

PMID- 11826893
TI  - Free radical production in photodynamically inactivated cells of Rhodotorula
      glutinis.
AB  - In an investigation of die-off of micro-organisms irradiated with high-intensity
      light, as might be expected in a space environment, the yeast Rhodotorula
      glutinis was used as a prototype. Previous results have shown that the yeast
      Rhodotorula glutinis can be photodynamically inactivated by laser radiation and
      by other intense light sources such as a xenon arc lamp. Experiments were
      conducted to determine if free radicals were involved in the inactivation of
      Rhodotorula glutinis when irradiated with light of wavelengths 300 nm and longer.
      Presumptive evidence that free radicals were involved in the photodynamic
      inactivation of the cells was found when it was shown that compounds capable of
      trapping free radicals were able to provide some protection to the cells. Further
      presumptive evidence that free radicals are involved was provided when it was
      shown that lipid peroxidation, which can be mediated by free radicals, is caused
      when the cells are irradiated. The actual production of free radicals was
      demonstrated by the detection of the presence of unpaired electron paramagnetic
      resonance spectra. These studies were conducted at both -30 degrees C and -160
      degrees C. It was found that free radicals were produced at both temperatures and
      that cysteine could decrease the free radical population at -30 degrees C but not
      at -160 degrees C.

PMID- 11826894
TI  - The detection of optical asymmetry in biogenic molecules by gas chromatography
      for extraterrestrial space exploration: sample processing studies.
AB  - Life detection instrumentation proposed for space missions is necessarily based
      on fundamental properties of life as we know it. Most biological life detection
      experiments attempt to elicit biological activity such as metabolism, growth, or
      reproduction. In addition to these approaches, which could be definitive, it is
      desirable to attack the problem of life detection as depending on some chemical
      attribute, since it may be most difficult to elicit a biological response.
      Fortunately, the property of natural optical activity in organics is synonymous
      with life, and can be measured by physicochemical methods. The phenomenon of
      optical activity arising from the selection of one of two possible isomers in
      living systems has been explained previously. Its detection in extraterrestrial
      samples would be prima facie evidence for the existence of life. For this reason,
      among others, gas chromatographic methods for the detection of optical asymmetry
      have been investigated and developed in recent years. We have preferred the
      diastereomeric route using (+)-2-butyl derivatives of amino acids and recently we
      have successfully made and separated derivatives of carbohydrates from
      glyceraldehyde through some hexoses. A scheme for isolating, purifying and
      derivatizing amino acids from soils has been devised and applied to rich and poor
      soils alike. Since the operations involved are simple as shown schematically, the
      utility of automated wet chemical approaches in space exploration is a distinct
      possibility.

PMID- 11826895
TI  - Degradation of paper mill water components in laboratory tests with pure cultures
      of bacteria.
AB  - The degradation of dissolved and colloidal substances from thermomechanical pulp
      (TMP) by bacteria isolated from a paper mill was studied in a laboratory slide
      culture system. Burkholderia cepacia strains hydrolysed triglycerides to free
      fatty acids, and the liberated unsaturated fatty acids were then degraded to some
      extent. Saturated fatty acids were not notably degraded. However, the branched
      anteiso-heptadecanoic fatty acid was degraded almost like the unsaturated fatty
      acids. About 30% of the steryl esters were degraded during 11 days, increasing
      the concentrations of free sterols. Approximately 25% of the dehydroabietic, and
      45% of the abietic and isopimaric resin acids were degraded during 11 days. The
      degree of unsaturation seemed to be of greater importance for the degradation of
      fatty acids than the molar mass. No degradation of dissolved hemicelluloses could
      be observed with any of the nine bacterial strains studied. Burkholderia cepacia
      strains and one Bacillus coagulans strain degraded monomeric fructose and glucose
      in winter TMP water, but in summer TMP water, with much lower sugar
      concentrations, also other Bacillus strains degraded monomeric sugars.

PMID- 11826896
TI  - Induction of the halobenzoate catabolic pathway and cometabolism of ortho
      chlorobenzoates in Pseudomonas aeruginosa 142 grown on glucose-supplemented
      media.
AB  - The aerobic cometabolism of ortho-substituted chlorobenzoates by Pseudomonas
      aeruginosa strain 142 growing on glucose-supplemented medium was analyzed. The
      strain, which can use 2-chlorobenzoate (2-CBA) and 2,4-dichlorobenzoate (2,4
      DCBA) as sole carbon and energy sources, showed high rates of 2-CBA metabolism in
      glucose-fed cells. In contrast, 2,4-DCBA was metabolized only after extended
      incubation of the full grown culture and depletion of glucose. In addition to the
      ortho-dehalogenation (ohb142) genes encoding the alpha and beta subunits of the
      oxygenase component of a 2-halobenzoate dioxygenase, strain 142 harbours a
      closely related ohbABCDFG gene cluster previously identified in P. aeruginosa JB2
      (ohbJB2). The genes for the chlorocatechol ortho-catabolic pathway were
      identified and sequenced in this strain, showing a near complete identity with
      the clcABD operon of the pAC27 plasmid. Relative quantification of mRNA by RT-PCR
      shows a preferential induction of ohb142 by 2-CBA, which is abolished in glucose
      grown cultures. The alternate ohbJB2 and clc genes were expressed preferentially
      in 2,4-DCBA grown cultures. Only ohbJB2 appears to be expressed in the presence
      of the carbohydrate. Detection of chlorocatechol-1,2-dioxygenase activity in 2,4
      DCBA plus glucose grown cultures suggests the presence of an alternate system for
      the ortho-cleavage of chlorobenzoates. The recruitment of elements from two
      halobenzoate dioxygenase systems with different induction patterns, together with
      a chlorocatechol degradative pathway not repressed by carbon catabolite, may
      allow P. aeruginosa 142 to cometabolize haloaromatics in carbohydrate grown
      cultures.

PMID- 11826897
TI  - Anaerobic degradation and dehalogenation of chlorosalicylates and salicylate
      under four reducing conditions.
AB  - The anaerobic biodegradability and transformation of the mono-and dichlorinated
      salicylates (2-hydroxybenzoates) was examined under denitrifying, Fe (III)
      reducing, sulfate reducing and methanogenic conditions. 3,6-Dichlorosalicylate
      and 6-chlorosalicylate are anaerobic microbial metabolites of dicamba, a widely
      used herbicide. Anaerobic microcosms were established with dicamba treated soil
      from Wyoming, and golf course drainage stream sediments from New Jersey, which
      were each spiked with salicylate, 3,6-dichlorosalicylate or one of the four
      monochlorosalicylate isomers. Salicylate was degraded under denitrifying,
      sulfidogenic and methanogenic conditions. In methanogenic enrichments 5
      chlorosalicylate and 3-chlorosalicylate were reductively dehalogenated to
      salicylate which was then utilized. Dehalogenation of monochlorinated salicylates
      to salicylate was also observed in denitrifying chlorosalicylate degrading
      cultures. The study revealed that the position of the chlorine substituent as
      well as the predominant electron accepting process affect the rate and extent of
      chlorosalicylate degradation in anoxic environments.

PMID- 11826898
TI  - Formaldehyde and methanol biodegradation with the methylotrophic yeast Hansenula
      polymorpha. An application to real wastewater treatment.
AB  - The application of methylotrophic yeast Hansenula polymorpha to the treatment of
      methanol and formaldehydecontaining wastewater was experimentally verified. A
      variety of real wastewater samples originating from chemical industry effluent
      were examined. The yeast cell culture could grow in the wastewater environment,
      revealing low trophic requirements and a very high adaptation potential to poor
      cultivation conditions. The proliferation of cells was accompanied by a
      concomitant xenobiotic biodegradation. Grown, preadapted cellular suspension at a
      density of about 1 x 10(7) cells/ml proved to be able to utilize formaldehyde
      present in wastewater at concentrations up to 1750 mg/l, levels toxic to most
      microorganisms. The biological waste treatment method presented shows the
      enhanced potential by means of specific enzymatic activities of monocarbonic
      compound oxidations through methylotrophic pathway reactions. The need to obtain
      mutants highly resistant to formaldehyde has also been rationalized.

PMID- 11826899
TI  - Purification and characterization of a salicylate hydroxylase involved in 1
      hydroxy-2-naphthoic acid hydroxylation from the naphthalene and phenanthrene
      degrading bacterial strain Pseudomonas putida BS202-P1.
AB  - 1-Hydroxy-2-naphthoate is formed as an intermediate in the bacterial degradation
      of phenanthrene. A monooxygenase which catalyzed the oxidation of 1-hydroxy-2
      naphthoate to 1,2-dihydroxynaphthalene was purified from the phenanthrene- and
      naphthalene-degrading Pseudomonas putida strain BS202-P1. The purified protein
      had a molecular weight of 45 kDa and required NAD(P)H and FAD as cofactors. The
      purified enzyme also catalysed the oxidation of salicylate and various
      substituted salicylates. The comparison of the Km and Vmax values for 1-hydroxy-2
      naphthoate and salicylate demonstrated a higher catalytic efficiency of the
      enzyme for salicylate as a substrate. A significant substrate-inhibition was
      detected with higher concentrations of 1-hydroxy-2-naphthoate. The aminoterminal
      amino acid sequence of the purified enzyme showed significant homologies to
      salicylate 1-monooxygenases from other Gram negative bacteria. It was therefore
      concluded that during the degradation of phenanthrene the conversion of 1-hydroxy
      2-naphthoate to 1,2-dihydroxynaphthalene is catalysed by a salicylate 1
      monooxygenase. Together with previous studies, this suggested that the enzymes of
      the naphthalene pathway are sufficient to catalyse also the mineralization of
      phenanthrene.

PMID- 11826901
TI  - Repeated inoculation as a strategy for the remediation of low concentrations of
      phenanthrene in soil.
AB  - Phenanthrene, a polycyclic aromatic hydrocarbon, becomes increasingly unavailable
      to microorganisms for degradation as it ages in soil. Consequently, many
      bioaugmentation efforts to remediate polycyclic aromatic hydrocarbons in soil
      have failed. We studied the effect of repeatedly inoculating a soil with a
      phenanthrene-degrading Arthrobacter sp. on the mineralization kinetics of low
      concentrations of phenanthrene. After the first inoculation, the initial
      mineralization rate of 50 ng/g phenanthrene declined in a biphasic exponential
      pattern. By three hundred hours after inoculation, there was no difference in
      mineralization rates between the inoculated and uninoculated treatments even
      though a large fraction of the phenanthrene had not yet been mineralized. A
      second and third inoculation significantly increased the mineralization rate,
      suggesting that, though the mineralization rate declined, phenanthrene remained
      bioavailable. Restirring the soil, without inoculation, did not produce similar
      increases in mineralization rates, suggesting absence of contact between cells
      and phenanthrene on a larger spatial scale (>mm) is not the cause of the
      mineralization decline. Bacteria inoculated into soil 280 hours before the
      phenanthrene was added could not maintain phenanthrene degradation activity. We
      suggest sorption lowered bioavailability of phenanthrene below an induction
      threshold concentration for metabolic activity of phenanthrene-degrading
      bacteria.

PMID- 11826900
TI  - Biotransformation kinetics of Pseudomonas putida for cometabolism of phenol and 4
      chlorophenol in the presence of sodium glutamate.
AB  - A kinetic model to describe the degradation of phenol and cometabolic
      transformation of 4-chlorophenol (4-cp) in the presence of sodium glutamate (SG)
      has been developed and validated experimentally. The integrated model accounts
      for cell growth, toxicity of 4-cp, cross-inhibitions among the three substrates,
      and the different roles of the specific growth substrate (phenol) and the
      conventional carbon source (SG) in the cometabolism of 4-cp. In this ternary
      substrate system, the overall phenol degradation and 4-cp transformation rates
      are greatly enhanced by the addition of SG since SG is able to attenuate the
      toxicity of 4-cp and therefore increase the cell growth rate. Model analysis
      indicates that the maximum specific degradation rate of phenol (0.819 mg (mg.h)(
      1)) is lowered by SG by up to 46% whereas the specific transformation rate of 4
      cp is not directly affected by the presence of SG. The competitive inhibition
      coefficient of 4-cp to phenol degradation (Ki,cp) and that of phenol to 4-cp
      transformation (Ki,ph) were determined to be 6.49 mg l(-1) and 0.193 mg l(-1),
      respectively, indicating that phenol imposes much larger competitive inhibition
      to 4-cp transformation than the converse. The model developed can simultaneously
      predict phenol degradation and 4-cp transformation, and is useful for dealing
      with cometabolism involving multiple substrates.

PMID- 11826902
TI  - [Axel Laurent-Christensen: a doctor "with feeling for snow"].
AB  - In 1950 the district medical officer of Qaqortoq/Julianehab, Axel Laurent
      Christensen retired after having served in this position since 1930. Afterwards,
      during the years 1950-55, he was a medical officer in Aklavik, NWT, Canada. Here
      he had the opportunity to compare the arctic Canadian health care with the
      Greenland health care system. In his diary, of which selected parts are given in
      the present paper, he has commented on the differences. In the 1950's the
      Canadian system was highly centralized with the well-equipped Charles Camsell
      Indian Hospital in Edmonton as the center. The Greenland health service, on the
      other hand, was decentralized, based on small surgically staffed peripheral
      hospitals. The development of these two health care systems during the past 50
      years has accentuated these differences. Estimated by the infant mortality, the
      efficiency of the Greenland health care system was superior to the Canadian
      during the 1950's, whereas in the 1990's, the Canadian health service is vastly
      superior.

PMID- 11826903
TI  - Metabolism of 2,4-dinitrotoluene (2,4-DNT) by Alcaligenes sp. JS867 under oxygen
      limited conditions.
AB  - Transformation of 2,4-dinitrotoluene (2,4-DNT) by Alcaligenes JS867 under varying
      degrees of oxygen limitation was examined. Complete 2,4-DNT removal was observed
      under oxygen excess with near stoichiometric release (83%) of nitrite. Average
      kinetic parameters were estimated based on a dual-Monod biokinetic model with 2,4
      DNT and O2 as growth limiting substrates. The negative impact of nitrite
      accumulation on the reaction rate was adequately described by inclusion of a
      noncompetitive inhibition term for NO2-. Under aerobic conditions, mumax, KsDNT,
      and KiNO were 0.058 (0.004)hr(-1), 3.3(+/-1.3) mg 2,4-DNT/L, and 1.2(+/-0.2)hr(
      1), respectively. At increasing oxygen limitation, rates of 2,4-DNT disappearance
      and nitrite production decreased and incomplete removal of 2,4-DNT commenced.
      JS867 was able to use NO2- as a terminal electron acceptor when grown on glucose
      or succinate under anaerobic conditions. However, during growth on 2,4-DNT and
      under O2-limited conditions, JS867 did not use released nitrite as electron
      acceptor. The nearly constant molar ratios of DNT removed over NO2- released
      under various degrees of oxygen limitation suggested that oxygenolytic
      denitration pathways continued. No evidence of nitroreduction was obtained under
      the examined oligotrophic conditions. JS867 displayed a high affinity for oxygen
      consumption with K(SO2) value of 0.285(+/-0.198) mg O2/L. Our results indicate
      that under oligotrophic conditions with 2,4-DNT as dominant carbon source, oxygen
      availability and nitrite accumulation may limit 2,4-DNT biomineralization, but
      the accumulation of reduced 2,4-DNT transformation products will be small.

PMID- 11826904
TI  - Degradation of alkali-lignin residues from solid-state fermentation of wheat
      straw by streptomycetes.
AB  - The ability of three Streptomyces strains to degrade alkali-lignin, produced from
      the treatment of wheat straw by the same organisms, was examined. Decolourisation
      and loss of alkali-lignin was only detected in cultures supplemented with
      ammonium as an inorganic N source. The pH of cultures supplemented with inorganic
      N reached lower pH than in those supplemented with yeast extract. From FT-IR
      spectra corresponding to the alkalilignin obtained from the same cultures, a
      degradation of carbohydrate component concomitant with a modification in the
      aromatic moiety of lignin could be inferred. The results indicate that
      streptomycetes are suitable for use in the treatment of alkali-lignin effluents
      from the biological treatment of wheat straw by the same organisms and therefore
      support the role for these organisms in the development of clean technologies in
      pulp and paper industry.

PMID- 11826905
TI  - Effects of olive mill wastewater addition in composting of agroindustrial and
      urban wastes.
AB  - In order to study the suitability of olive mill wastewater (OMW) for composting,
      this liquid waste was added to two different mixtures of agroindustrial and urban
      wastes and the composting process was compared with two other piles of similar
      composition, but without OMW. These four piles were studied in a pilot plant
      using the Rutgers static pile system. The addition of OMW produced a greater
      proportion of degradable organic matter or a higher degradation rate, higher
      electrical conductivity values, greater losses of total N and lower nitrification
      than in piles without OMW. Its addition also restricted the increase of the
      cation exchange capacity and provoked the appearance of phytotoxicity or a longer
      persistence of phytotoxicity. However, in general, all the composts showed
      increases in the cation exchange capacity, the percentage of humic acid-like
      carbon, the polymerisation ratio of these humic substances (which revealed that
      the organic matter had been humified during composting) and the germination
      index, the latter indicating the reduction of phytotoxicity during the process.

PMID- 11826906
TI  - Bioremediation of DDT in soil by genetically improved strains of soil fungus
      Fusarium solani.
AB  - Bioremediation of DDT in soil by genetically improved recombinants of the soil
      fungus Fusarium solani was studied. The parent strains were isolated from soil
      enriched with DDD or DDE (immediate anaerobic and aerobic degradation products of
      DDT), as further degradation of these products are slow processes compared to the
      parent compound. These naturally occurring strains isolated from soil, however,
      are poor degraders of DDT and differed in their capability to degrade its
      metabolites such as DDD, DDE, DDOH and DBP and other organochlorine pesticides
      viz. kelthane and lindane. Synergistic effect was shown by some of these strains,
      when grown together in the medium containing DDD and kelthane under mixed culture
      condition. No synergism in DDE degradation was observed with the strains isolated
      from enriched soil. DDD-induced proteins extracted from individual culture
      filtrate (exo-enzyme) when subjected to SDS-Polyacrylamide Gel Electrophoresis
      (SDS-PAGE) showed complementary polypeptide bands in these strains i.e., each
      strain produced distinct DDD degrading polypeptide bands and the recombinant or
      hybrid strains produced all of the bands of the two parents and degraded DDD
      better than the parental strains. Recombinant hybrid strains with improved
      dehalogenase activity were raised by parasexual hybridisation of two such
      complementary isolates viz. isolate 1(P-1) and 4(P-2) showing highest
      complementation and are compatible for hyphal fusion inducing heterokaryosis.
      These strains are genetically characterised as Kel+Ben(R)DBP-Lin- and Kel
      Ben(r)DBP+Lin+ respectively. Recombinants with mixed genotype, i.e.,
      Kel+Ben(R)DBP+Lin+ showing superior degradation quality for DDT were selected for
      bioremediation study. Recombination was confirmed by polypeptide band analysis of
      DDD induced exo-proteins from culture filtrate using SDS-Polyacrylamide Gel
      Electrophoresis (PAGE) and RAPD (Random Amplified Polymorphic DNA) of genomic DNA
      using PCR (Polymerase Chain Reaction) technique. SDS-PAGE showed combination of
      DDD induced polypeptide bands characteristic of both the parents in the
      recombinants or the hybrids. PCR study showed the parent specific bands in the
      recombinant strains confirming gene transformation.

PMID- 11826907
TI  - Protein degradation during anaerobic wastewater treatment: derivation of
      stoichiometry.
AB  - The stoichiometry of reactions that describe protein degradation in anaerobic
      treatment systems were investigated. A methodology was developed to describe
      protein degradation to organic acids using a single reaction step. The reactions
      for individual amino acid fermentation and their mediating organisms were
      reviewed. The dominant fermentation pathways were selected based on a number of
      assumptions. Using the amino acid content of a model protein, it was then
      possible to determine stoichiometric coefficients for each major organic acid
      product in the overall degradation of the protein. The theoretical coefficients
      were then compared to those determined from two experimental runs on a
      continuously-fed, well-mixed, laboratory-scale anaerobic wastewater treatment
      system. In general, the coefficients compared well thus validating the use of a
      single reaction step for the overall catabolic reaction of protein degradation to
      organic acids. Furthermore, even when the protein concentration in feed or the
      feed flow rate was doubled, the amino acid fermentation pathways were found to
      occur predominantly by only one pathway. Although the choice of Stickland
      reactions over uncoupled degradation provided good comparisons, an electron
      balance showed that only about 40% of the amino acids could have proceeded
      coupled to other amino acid reactions. Uncoupled degradation of the remaining
      amino acids must have relied on the uptake of hydrogen produced from these
      reactions by hydrogen-consuming methane bacteria.

PMID- 11826908
TI  - Biodegradation of lignocellulosic waste by Aspergillus terreus.
AB  - Biodegradation of lignocellulosic waste by Aspergillus terreus is reported for
      the first time. This isolate produced 250 CMCase (carboxymethyl cellulase or
      endoglucanase) U.ml(-1) and biodegraded hay and straw during 3 days and the
      biomass production on straw was 5g.L(-1) dry weight from 0.25 cm2 inoculated
      mycellium. This strain secreted endocellulases and exocellulases in the culture
      medium, but some of the enzymes produced, remained cell membrane bound. Cell
      bound enzymes were released by various treatments. The highest amount of
      endoglucanase and exoglucanase was released when the cells were treated with
      sonication. Aspergillus terreus was added to two tanks containing sugar
      wastewater and pulp manufacturing waste, as a seed for COD removal. This fungus
      reduced the COD by 40-80 percent, also, ammonia was reduced from 14.5 mM to 5.6
      mM in sugar beet wastewater. The effects of crude enzyme of this fungus for COD
      removal was studied.

PMID- 11826909
TI  - Thermodynamic yield predictions for biodegradation through oxygenase activation
      reactions.
AB  - Activation reactions involve modification of recalcitrant substrates to forms
      that are more readily degradable. These reactions require specialized enzymes and
      cosubstrates, including molecular oxygen and reduced electron carriers. In these
      reactions, microorganisms invest electrons and cannot capture energy or carbon
      for synthesis. The subsequent degradation of the intermediates formed in
      activation reactions releases electrons, energy, and carbon that the organisms
      use for growth. The overall yield is reduced due to the required activation
      investments. A mathematical method to predict cell yields of oxygenase activation
      reactions is developed using electron and energy balances. Predicted yields are
      compared with experimental yields for methane, organic chelating agents, and
      aromatic hydrocarbons.

PMID- 11826910
TI  - Prevalence of asthma and related symptoms in primary school children of Isfahan,
      Iran, in 1998.
AB  - As developing countries adopt an industrialized style of living, an increase in
      asthma prevalence can be expected. A cross sectional study was undertaken to
      evaluate the prevalence rates of asthma and related symptoms and clinical
      findings in Isfahan, Iran. A randomly selected population of Isfahan primary
      school children, consisting of 3,982 children aged 6 to 11 was enrolled in the
      study. Parents completed a Persian questionnaire modified from ISAAC and ECRHS
      questionnaires. The returned 3,828 (96.1%) questionnaires were reviewed and 686
      children suffering from asthma or any of the related symptoms were invited for
      further evaluations. In this stage 655 children (95.5%) underwent a medical
      interview and physical examinations, of which 415, underwent post exercise
      spirometry and body-plethysmography. The prevalence rates for previously
      diagnosed asthma, dyspnea and wheezing ever, dyspnea and wheezing in the last 12
      months and frequently recurring dyspneal attacks were 0.71%, 7.6%, 3.9% and 1.6%,
      respectively. Wheezing was heard upon auscultation of the chests of 70 children
      (10.7%). Forced expiratory volume in 1st second (FEV1) < 80% of prediction was
      recorded in 3.1% of the children, other findings included reduced peak expiratory
      flow rate (PEF), mean expiratory flow 25 to 75 percent (FEF 25-75), forced
      expiratory flow at 75% of FVC (FEF 75), and increased residual volume (RV) and
      air-ways resistance in 4.3%, 10.6%, 21.2%, 30.1% and 63.2% of the pupils,
      respectively. We conclude that asthma screening programs employing clinical
      methods should be encouraged, but measurement of airway resistance is not a
      suitable tool for epidemiologic studies.

PMID- 11826911
TI  - A double-blind, placebo-controlled, and randomized study of loratadine
      (Clarityne) syrup for the treatment of allergic rhinitis in children aged 3 to 12
      years.
AB  - Allergic rhinitis is a common disease in children, and antihistamines are the key
      medication. However, traditional tablets are not convenient and lead to low
      compliance in young children. The aim of this double-blind, placebo-controlled,
      parallel, randomized study was to evaluate the effectiveness and safety of
      loratadine syrup for the treatment of children aged 3 to 12 years with allergic
      rhinitis. Sixty children with allergic rhinitis due to dust mites were enrolled.
      They were randomized into 2 parallel groups: one group received loratadine syrup
      5 mg or 10 mg daily for 3 weeks, and the other group received placebo. The
      patients returned to special clinics for symptoms evaluation at day 7 and day 21,
      and the parents were requested to record disease severity daily. Both
      evaluations, physician's and parents', were recorded with a 4-point scale for 5
      symptoms: sneezing, rhinorrhea, nasal congestion, nasal itching and ocular
      symptoms. Forty-six patients completed the study, 22 in the loratadine group and
      24 in the placebo group. At the initial visit, the total symptom score (TSS) in
      both groups was not significantly different (p = 0.39). The TSS of the loratadine
      syrup group at day 7 and day 21 was lower than those of the placebo group (p =
      0.003, p = 0.06). The daily card scores in the experimental group were also
      significantly lower than those of the placebo group (week 1, p = 0.014; week 2, p
      = 0.029; week 3, p = 0.014). No adverse reactions were recorded in both groups.
      This study revealed that loratadine syrup 5 mg or 10 mg once a day improved
      symptom scores of children with allergic rhinitis effectively and safely.

PMID- 11826912
TI  - Theophylline toxicity in Thai children.
AB  - Theophylline is a useful drug in the treatment of respiratory diseases with
      bronchospasm but it has very narrow safety margin. The study was carried out in
      44 admitted Thai children with plasma theophylline levels > 20 microg/ml to
      determine the association between blood levels and symptoms of theophylline
      toxicity. The prevalence of theophylline toxicity (plasma theophylline level > 20
      microg/ml) in Thai children is about 11%. Thirty-four percent of the patients who
      had theophylline levels less than 30 microg/ml and 78% of those who had levels
      more than 30 microg/ml had symptoms of theophylline toxicity. The symptoms were
      related to the gastrointestinal tract (34%), cardiovascular system (18.2%),
      neurological system (6.8%) and metabolism (54.5%). The possible causes of
      theophylline toxicity were respiratory tract infection, theophylline overdosage,
      interaction with other drugs, impairment of liver function, congenital heart
      disease and theophylline usage in neonates. Theophylline is still a useful drug
      but should be used with caution. Theophylline levels should be checked in every
      child who receives theophylline.

PMID- 11826913
TI  - Effect of G-CSF on peripheral blood progenitor cell mobilization and collection
      from healthy donors.
AB  - We studied granulocyte colony-stimulating factor (G-CSF) mediated peripheral
      blood progenitor cells (PBPC), which were mobilized and collected from healthy
      donors for allogeneic transplantation. A total of 26 donors, age ranged from 21
      41 years were mobilized with G-CSF at a dose of 7.5 microg/kg/day subcutaneously
      for 5 days and the collection was started on day 5. The CD34 cell counts reached
      a maximum on day 5 and subsequently declined despite continually given G-CSF.
      White blood cells (WBC), absolute neutrophil counts (ANC), absolute lymphocytes
      (AL) and their subsets, absolute mononuclear cells (AMNC), colony-forming unit
      granulocyte, macrophage (CFU-GM) and CD34+ cells were increased about 6, 9, 2, 3,
      34 and 40-fold, respectively, but red blood cells (RBC), hematocrit (Hct) and
      platelets (Pit) decreased on day 5 when compared to day 0. All parameters
      decreased after stem cell collection. For stem cell collection by Cobe Spectra,
      we used a blood volume of 19.27 +/- 4.65 liters, flow rate of 60.53 +/- 10.03
      ml/minute, acid citrate dextrose solution (ACD)/blood ratio of 1:13.31, the final
      product volume was 314.14 +/- 72.24 ml, collection time was 325.40 +/- 73.36
      minutes and one or two procedures were sufficient. The correlation between the
      number of CD34+ cells/kg, CFU-GM/kg and MNC/kg found in the harvested product and
      CD34 cells can be used for determining the necessary amount of progenitor cells
      for transplantation.

PMID- 11826914
TI  - Successful allogeneic peripheral blood stem cell transplantation in Wiskott
      Aldrich Syndrome Patients: first report in Thailand.
AB  - Wiskott-Aldrich syndrome (WAS), an X-linked recessive disorder, is characterized
      by primary progressive T cell immunodeficiency, impaired antipolysaccharide
      antibody production, eczema, and thrombocytopenia. Stem cell transplantation is
      the only curative therapy. To evaluate the use of allogeneic peripheral stem cell
      transplantation (PBSCT) in this group of patients, we performed allogeneic PBSCT
      in two WAS patients (3 and 12 years old). The conditioning regimen consisted of
      busulfan 4 mg/kg/day for 4 days, and cyclophosphamide 50 mg/kg/day for 4 days.
      Graft-versus-host disease prophylaxis was consistent with cyclosporin A and
      methotrexate. Peripheral blood stem cells were collected from their brother
      donors (6 and 16 years old) by continuous flow leukapheresis after mobilization
      with granulocyte-colony-stimulating factor at a dose of 7.5 microg/kg/day for 5
      days. Both recipients achieved neutrophils engraftment on days 11 and 12. The
      first patient achieved platelets engraftment on day 30. The second patient did
      not have platelet count below 20.0 x 10(9)/l during PBSCT procedure. Both did not
      develop acute or chronic graft-versus-host disease. At present, they are healthy
      after PBSCT. The follow up time after transplantation is 1,170 days and 269 days,
      respectively. Allogeneic PBSCT is economically feasible for WAS. The cost of
      PBSCT in Thailand is 20 to 30% less than bone marrow and cord blood stem cell
      transplantation. The cost of the transplant procedure for each patient in
      Thailand is US $ 12,000. This study is the first report of a successful stem cell
      transplantation in WAS patients in Thailand.

PMID- 11826915
TI  - Immunohistochemical study of c-erbB-2 expression in primary breast cancer.
AB  - An immunohistochemical (IHC) study of the c-erbB-2 protein was performed in
      paraffin-embedded tissues from 506 primary breast carcinomas. An overexpression
      of c-erbB-2 was detected in 32% of the tumors and was correlated with a negative
      estrogen receptor status, increasing tumor size as well as axillary lymph node
      involvement. The five-year disease free survival was analyzed in 183 patients who
      have been followed for at least five years. No statistically significant
      association of c-erbB-2 status with survival was shown. However, longer survival
      in women over 50 years compared to under 50 years of age was detected among the c
      erbB-2 positive patients. In the multivariate Cox's regression analysis, lymph
      node and vascular invasions were independent prognostic indicators among these
      patients. But c-erbB-2 status and other factors did not predict the relapse of
      breast cancer. However, these data may not negate the benefit of c-erbB-2
      detected by IHC for identification of patients who have a poor prognosis and
      require more aggressive adjuvant therapy. Further studies in a larger group of
      patients with longer follow-up time may provide more valid information.

PMID- 11826916
TI  - Methodology evaluation of a new immunoturbidimetric method for measuring serum
      soluble transferrin receptor.
AB  - The value of soluble transferrin receptor (sTfR) detected in serum is closely
      related to erythroid TfR turnover rate. An increased erythropoietic activity
      causes an increase in the sTfR level. Therefore, it is a useful test for
      monitoring the erythropoiesis. In this study, a new immunoturbidimetric method
      for automated measurement of sTfR was evaluated for its performance
      characteristics. Imprecision studies on patients' sera with 1.01 mg/l and 2.94
      mg/l concentrations yielded within-run CVs of 1.16% and 1.27%. Accuracy analysis
      of the test by using the low and high control kit sera with 1.45 mg/l and 5.41
      mg/l concentrations were 89.06% and 95.41%, respectively. The evaluation was also
      performed in 60 individual pediatric subjects, 30 beta-thalassemia/HbE and 30
      control pediatric subjects. There is a statistically significant difference of
      sTfR between both groups (p < 0.0005, 95% Cl = 9.457-14.124). Ninety-five percent
      of matched pediatric subjects had sTfR level < or = 2.670 mg/l and 93.33% of
      patients diagnosed beta-thalassemia/HbE had values > 2.670 mg/l. In conclusion,
      this immunoturbidimeteric test yields good laboratory performance characteristics
      in terms of precision and accuracy.

PMID- 11826917
TI  - Role of cytokines in immune response to pulmonary tuberculosis.
AB  - Immunopathogenesis of tuberculosis needs to be explored in search of a proper
      vaccine as well as for adjunctive immunotherapy particularly in patients with
      drug resistant tuberculosis. In tuberculosis, IFN-gamma, a product of T
      lymphocytes, contributes to protective immunity against M. tuberculosis by
      activating macrophages to a more effective elimination of these organisms.
      Interleukin-12 and interleukin-18 are macrophage products that favor the
      development of Th1 type of protective immune response. Production of these
      cytokines may not only facilitate granuloma formation and bacillary elimination
      but may also cause local tissue necrosis and systemic effects such as fever and
      wasting, due to the release of TNF-alpha into the circulation. The production of
      anti-inflammatory cytokines such as IL-10, TGF-beta and IL-4 in response to M.
      tuberculosis may down regulate the immune response and limit tissue injury by
      inhibiting excessive inflammatory response. These cytokines, if produced in
      excess, may result in failure to control infection resulting in widely
      disseminated tuberculosis. It is the balance between the inflammatory and
      protective immune response that determines the outcome of tuberculosis infection.
      In that context, increased IFN-y as against reduced TNF-alpha probably suggests a
      better outcome. Similarly, an effective vaccine has to stimulate a precise
      combination of T cells and cytokines needed for the many aspects of immune
      response and a potent immunotherapeutic agent may require to encompass the
      multiple parameters to be of therapeutic relevance.

PMID- 11826918
TI  - Eosinophilic gastroenteritis in children-report of one case.
AB  - Eosinophilic gastroenteritis is rare in pediatric patients. The three main
      manifestations, defined by Klein et al. in 1970, were (a) predominant mucosal,
      (b) predominant muscular-layer, and (c) predominant subserosal disease. The
      predominant subserosal type is the rarest of the three. We report on a 43-month
      old boy who, on admission, suffered from recurrent abdominal pain, vomiting and
      diarrhea for one week, with ascites and pleural effusion noted. The white blood
      cell (WBC) count of ascites fluid was 8,000/mm3, with a differential count of 99%
      eosinophils. The peripheral WBC count was 44,000/mm3, with 78% eosinophils. Three
      days after diagnosis, ascites, pleural effusion and other gastrointestinal
      symptoms were gradually relieved using steroid therapy, with the peripheral
      eosinophil count returning to normal. The steroid therapy was discontinued after
      two months with tapering dose. The boy was in good health with no recurrence of
      symptoms in a follow-up conducted after one year.

PMID- 11826919
TI  - In vivo kinematic comparison of posterior cruciate ligament retention or
      sacrifice with a mobile bearing total knee arthroplasty.
AB  - Video fluoroscopy and computer photogrammetry was used to evaluate 20 knees with
      posterior cruciate ligament (PCL) retaining and 19 knees with PCL sacrificing
      total knee arthroplasties (TKAs) with a mobile bearing total condylar prosthesis
      compared with 10 normal patients. In extension, femorotibial contact was
      posterior for TKA patients (P<.05) and demonstrated anterior translation from 60
      degrees-90 degrees flexion. However, posterior rollback with limited translation
      was seen from 0 degrees-40 degrees, which may reflect the high congruity of this
      prosthesis. Fifty percent of meniscal bearing implants demonstrated bearing
      translation. Kinematics and weight-bearing range of motion were similar with PCL
      retention or sacrifice.

PMID- 11826920
TI  - Clinical analysis of the pivot shift tests: description of the pivot drawer test.
AB  - A clinical analysis of the pivot shift was performed by evaluating 100 patients
      with unilateral anterior cruciate ligament (ACL) insufficiency in an office
      setting. Each patient was examined in a random order using the Macintosh, Losee,
      Hughston, Slocum, pivot drawer, and flexion rotation drawer versions of the pivot
      shift test. Pathologic anterior tibial displacement was estimated with the
      Lachman test and quantitatively measured using the KT-1000 knee ligament
      arthrometer. Pivot shift was graded as 0 (absent), grade I (slight), grade II
      (definite subluxation), and grade III (subluxation and momentary locking). The
      presence or absence of any degree of pivot shift was correlated with the
      arthroscopic finding of a torn ACL. Results indicated the "drawer type" tests
      were significantly more sensitive than other versions of the pivot shift because
      they can be performed without causing significant pain and muscle spasm, and the
      limb position maximizes pathologic coupled motion. A correlation between
      increasing displacement estimated with the Lachman test and measured displacement
      with the KT-1000 arthrometer revealed that as pathologic displacement increases
      so does the grade of the Slocum, pivot drawer, and flexion rotation drawer tests.
      We recommend using the pivot drawer or flexion rotation drawer as a standard
      method for assessing the pivot shift phenomenon.

PMID- 11826921
TI  - The snapping biceps femoris tendon.

PMID- 11826922
TI  - Healing of articular cartilage: a review.
AB  - Currently, there is no one human technique that stands out as being better than
      another. The results of curettement or microfracture remain as good as anything
      else that is available. The healing in these defects seems to be as good as those
      that are achieved with osteochondral tissue graft or with chondrocyte culture
      techniques. The controlled prospective treatment of cartilage defects that
      compares these techniques to traditional methods has not been done.

PMID- 11826923
TI  - The treatment of articular cartilage defects using microfracture and debridement.

PMID- 11826924
TI  - Autologous chondrocyte implantation.
AB  - Rationale for the treatment of cartilage damage in younger patients depends on a
      thorough understanding of the predisposing factors for the chondrosis and the
      stage of disease. Implantation with autologous cultured chondrocytes allows for
      resurfacing of larger defect areas with reproducibly good/excellent results in
      90% of patients with isolated lesions of the femoral condyle. Patellar lesions
      also may be successfully treated (approximately 75% improved) but strict
      attention must be given to correction of malalignment. Results in patients with
      tibial and salvage lesions are encouraging; however, these results should be
      viewed with caution due to the small number of patients with 2-year follow-up.
      Autologous chondrocyte implantation involves an open technique with the inherent
      disadvantages of adhesions and a more prolonged recovery. However, these
      disadvantages must be weighed against the procedure's ability to produce a
      hyaline-type tissue with greater durability than fibrocartilage repairs produced
      by traditional marrow-stimulation techniques. We recommended matching the
      treatment procedure to patient expectations and lesion/demographic
      characteristics. Based on the available literature. algorithms have been
      published that recommend autologous chondrocyte implantation be reserved as first
      line treatment for high-demand patients with large lesions (>2 cm2) and as
      revision therapy in patients with lesions of all sizes, regardless of patient
      demand, who have failed alternative marrow stimulation techniques.

PMID- 11826925
TI  - Osteochondral tissue transfers.

PMID- 11826926
TI  - Articular cartilage regeneration: a matter of time and creativity.

PMID- 11826927
TI  - Response of hamstring and patellar tendon grafts for anterior cruciate ligament
      reconstruction during cyclic tensile loading.
AB  - The efficacy of anterior cruciate ligament (ACL) reconstruction in the knee using
      hamstring tendon or patellar tendon grafts is thought to depend on the relative
      amounts of graft elongation, or creep, following postoperative rehabilitation. In
      this study, the creep responses of the tendinous portions of these two graft
      types were compared during 1 hour of cyclic loading to 200 N at 1 Hz. In the
      hamstring tendon grafts, strains were measured in both the tissue and in the
      length-augmentation tape to identify the relative contribution of this particular
      graft fixation to overall creep. Differences in tissue strain between graft types
      during cyclic loading were not statistically significant. For both types of
      grafts, overall graft length significantly increased after 3600 cycles while
      tissue creep was not significant. The greatest creep in the hamstring tendon
      grafts occurred at the tissue-tape interface, indicating a potential disadvantage
      of this composite graft construct.

PMID- 11826928
TI  - The epistemology of epidemiology.

PMID- 11826929
TI  - Breast self-examination.

PMID- 11826930
TI  - Breast self-examination.

PMID- 11826932
TI  - Breast self-examination.

PMID- 11826931
TI  - Breast self-examination.

PMID- 11826933
TI  - Breast self-examination.

PMID- 11826934
TI  - Breast self-examination.

PMID- 11826935
TI  - Breast self-examination.

PMID- 11826937
TI  - Assessing the quality of clinical practice guidelines.

PMID- 11826936
TI  - Assessing the quality of clinical practice guidelines.

PMID- 11826938
TI  - Tell me what troubles you most.

PMID- 11826939
TI  - Variations in mortality rates among Canadian neonatal intensive care units.
AB  - BACKGROUND: Most previous reports of variations in mortality rates for infants
      admitted to neonatal intensive care units (NICUs) have involved small groups of
      subpopulations, such as infants with very low birth weight. Our aim was to
      examine the incidence and causes of death and the risk-adjusted variation in
      mortality rates for a large group of infants of all birth weights admitted to
      Canadian NICUs. METHODS: We examined the deaths that occurred among all 19 265
      infants admitted to 17 tertiary-level Canadian NICUs from January 1996 to October
      1997. We used multivariate analysis to examine the risk factors associated with
      death and the variations in mortality rates, adjusting for risks in the baseline
      population, severity of illness on admission and whether the infant was outborn
      (born at a different hospital from the one where the NICU was located). RESULTS:
      The overall mortality rate was 4% (795 infants died). Forty percent of the deaths
      (n = 318) occurred within 2 days of NICU admission, 50% (n = 397) within 3 days
      and 75% (n = 596) within 12 days. The major conditions associated with death were
      gestational age less than 24 weeks (59 deaths [7%]), gestational age 24-28 weeks
      (325 deaths [41%]), outborn status (340 deaths [42%]), congenital anomalies (270
      deaths [34%]), surgery (141 deaths [18%]), infection (108 deaths 114%]), hypoxic
      ischemic encephalopathy (128 deaths [16%]) and small for gestational age (i.e.,
      less than the third percentile) (77 deaths [10%]). There was significant
      variation in the risk-adjusted mortality rates (range 1.6% to 5.5%) among the 17
      NICUs. INTERPRETATION: Most NICU deaths occurred within the first few days after
      admission. Preterm birth, outborn status and congenital anomalies were the
      conditions most frequently associated with death in the NICU. The significant
      variation in risk-adjusted mortality rates emphasizes the importance of risk
      adjustment for valid comparison of NICU outcomes.

PMID- 11826940
TI  - The Ontario Family Medicine Residents Cohort Study: factors affecting residents'
      decisions to practise obstetrics.
AB  - BACKGROUND: The number of family physicians practising obstetrics in Canada is
      declining. On the assumption that factors related to the obstetrics training of
      family medicine residents may be influencing this trend, we conducted a cohort
      study of residents' stated intentions with regard to practising obstetrics, their
      educational experiences and their subsequent obstetric practice. METHODS: We
      followed a cohort consisting of all residents who enrolled in family medicine
      residency programs in Ontario in 1994 and 1995. The data, collected by mail-in
      survey at entry to, during and 2 years after completion of the 2-year training
      programs, consisted of residents' characteristics, stated plans during residency
      to practise obstetrics, obstetric experiences during training, attitudes and
      opinions related to obstetrics, and actual practice 2 years after completion of
      residency. We used logistic regression to determine the factors influencing
      whether a family physician practises obstetrics after graduation. RESULTS: Of the
      498 residents who started programs in 1994 and 1995, 480 were eligible for
      inclusion, although not all of those eligible responded to the various surveys.
      At entry into the residency programs, 216 (52%; 95% confidence interval [CI] 47
      57%) of the 411 respondents expressed an intention to practise obstetrics. By the
      end of residency, the proportion intending to practise obstetrics had fallen to
      17% (95% CI 13-22%; 46 of 274 respondents), and only 16% (95% CI 12% to 20%) were
      actually practising intrapartum obstetrics (i.e., delivering babies) 2 years
      later. The proportions of residents in the 7 Ontario family medicine programs who
      were actually practising obstetrics 2 years later ranged from 2% of those from
      the University of Western Ontario to 38% of those from Thunder Bay. Three factors
      were independently associated with practising intrapartum obstetrics 2 years
      after completing residency: intention at the end of residency to practise
      intrapartum obstetrics (odds ratio [OR] 11.7, 95% CI 3.1-44.7, p = 0.001), not
      having the opinion that intrapartum care is too disruptive of personal life (OR
      9.1, 95% CI 1.5-55.5, p = 0.02) and practising in a community of 15 000 or fewer
      people (OR 6.0, 95% CI 1.8-19.4, p = 0.003). INTERPRETATION: Residents who have
      positive attitudes toward obstetrics at the end of their training and who intend
      at that time to perform deliveries are more likely to be doing so 2 years later,
      especially if they practise in communities of 15,000 or fewer people.

PMID- 11826941
TI  - Use of postmenopausal estrogen replacement therapy from 1981 to 1997.

PMID- 11826942
TI  - Variations in mortality rates among Canadian neonatal intensive care units:
      interpretation and implications.

PMID- 11826943
TI  - What's in a name? Reporting data from public institutions.

PMID- 11826944
TI  - Nephrology in practice: a new series.

PMID- 11826945
TI  - When statistics provide unsatisfying answers: revisiting the breast self
      examination controversy.

PMID- 11826947
TI  - Rosiglitazone (Avandia) and pioglitazone (Actos) and heart failure.

PMID- 11826946
TI  - Clinical nutrition: 3. The fuzzy boundary between nutrition and
      psychopharmacology.

PMID- 11826948
TI  - Streptococcus pneumoniae infection in children: vaccine implications.

PMID- 11826949
TI  - Voluntary recall of ephedra products not enough, MD says.

PMID- 11826951
TI  - Scopes of practice.

PMID- 11826950
TI  - Bittersweet victory for CMA past president.

PMID- 11826952
TI  - Sequential comparison of peptides containing half-cystine residues from
      ovalbumins of six avian species.
AB  - Hen ovalbumin contains one cystine disulfide (Cys73-Cys120) and four cysteine
      sulfhydryl groups (Cys11, Cys30, Cys367, and Cys382) in a single polypeptide
      chain of 385 amino acid residues. To investigate whether or not such a structure
      is shared by related avian species, the contents of disulfide-involved half
      cystine residues and their positions in the primary structure of ovalbumins from
      five species were compared with those of hen ovalbumin. Ovalbumins were alkylated
      with a fluorescent dye, IAEDANS, under disulfide-reduced and disulfide-intact
      conditions and digested with a number of proteolytic enzymes. The sequences were
      deduced from peptides containing half-cystine residues labeled with the
      fluorescent dye. The results showed that the number of free cysteine sulfhydryl
      groups of ovalbumins was different among the species, three for guinea fowl and
      turkey (Cys11, Cys367, and Cys382); and two for Pekin duck, mallard duck, and
      Emden goose (Cys11 and Cys331). On the other hand, a single intrachain disulfide
      bond could be identified from ovalbumins of five species using a combination of
      peptide mapping and N-terminal amino acid sequencing analysis under reduced and
      non-reduced conditions, in which the intrachain disulfide bond was like that of
      hen ovalbumin (Cys73-Cys120). The results also indicated that the variations in
      amino acid sequences on these peptides containing half-cystine residues bear a
      close relationship with the phylogeny of the six species.

PMID- 11826953
TI  - Pressure distribution measurement in biting surimi gels with molars using a
      multiple-point sheet sensor.
AB  - The bite force of three surimi gels with molars was measured in the mouth using a
      multiple-point sheet sensor. A peak force appeared at the breaking point of each
      sample, and then the force increased again, accompanied by a decrease in the
      opening between the upper and lower teeth. Low values in the peak force,
      pressure, and time at the first peak, the time at which the maximum contact area
      was engaged, impulse, and slope of bite curve were observed in samples with low
      breaking force and low breaking deformation found by the mechanical measurement
      of gel strength, and with less toughness in the sensory assessment. The duration
      of the bite force, the second peak time, and active bite pressure at the second
      peak did not change with a change in the surimi texture. The active pressure at
      the breaking point of each gel was affected by gel strength, while that at the
      second peak was independent of the gel strength.

PMID- 11826954
TI  - Induction of 4-hydroxycinnamate decarboxylase in Klebsiella oxytoca cells exposed
      to substrates and non-substrate 4-hydroxycinnamate analogs.
AB  - The 4-hydroxycinnamate decarboxylase (4-HCD)-inducing activity of several
      substrate analogs toward Klebsiella oxytoca was investigated. Four E-cinnamate
      class compounds, E-4-hydroxycinnamic acid (1), caffeic acid (2), ferulic acid (3)
      and E-2,4-dihydroxycinnamic acid (4), all of which were accepted as substrates,
      all of which were accepted as substrates of 4-HCD, enable K. oxytoca cells to
      induce the decarboxylase at a 2.0 mM concentration, while five non-substrate
      compounds of the E-cinnamate class so far tested were completely inactive.
      However, 6-hydroxy-2-naphthoic acid (11) and 7-hydroxycoumarin 3-carboxylic acid
      (14), both of which are non-cinnamate-class analogs of the substrate, acted as
      strong 4-HCD inducers, even at a 0.5 mM concentration. The 4-HCD-inducing
      activities of compounds 11 and 14 at 0.5 mM were 10-12-fold higher than that of
      substrate 1. Compound 11 maintained its 4-HCD-inducing activity toward cultured
      cells through the late-log and stationary phases, unlike 1 that induced 4-HCD
      only in the early log phase. SDS-PAGE electrophoresis of protein mixtures from
      the cultured cells exposed to any 4-HCD inducer indicated that the 21.5 kDa
      protein was always present.

PMID- 11826955
TI  - Stable isotope-labeling studies on the oxidative coupling of caffeic acid via o
      quinone.
AB  - The formation of ortho-quinone from ortho-diphenol is a key step in its
      dimerization. An NMR analysis of the oxidation of 3,4-dihydroxycinnamic acid
      (caffeic acid) by NaIO4 revealed the formation of 3-(3',4'-dioxo-1',5'
      cyclohexadienyl) propenoic acid (o-quinone) prior to the formation of furofuran
      type lignan 4,8-exo-bis (3,4-dihydroxyphenyl)-3,7-dioxabicyclo[3.3.0]octane-2,6
      dione. Both electrolytic and enzymatic oxidation of caffeic acid also generated o
      quinone. The yields of o-quinone from caffeic acid were quantified by NMR and
      HPLC analyses. A stable isotope-labeling study of the formation of lignans
      directly proved the random radical coupling of semiquinone radicals formed from a
      set of caffeic acid and o-quinone.

PMID- 11826956
TI  - Isotope ratio by HRGC-MS of citrus Junos tanaka (yuzu) essential oils: m/z
      137/136 of terpene hydrocarbons.
AB  - The isotope ratios of monoterpene hydrocarbons in Citrus junos Tanaka (yuzu)
      essential oils from different origins were determined by ordinary high-resolution
      gas chromatography-mass spectrometry (HRGC-MS). Both intensities of the molecular
      mass peaks (m/z 136) and of the isotope peaks (m/z 137) of monoterpene
      hydrocarbons were measured by single-ion monitoring with an MS analysis. The
      isotope ratios (m/z 137/136) of the ten monoterpene hydrocarbons commonly
      contained in citrus essential oils, alpha-pinene, beta-pinene, sabinene, myrcene,
      alpha-phellandrene, alpha-terpinene, limonene, gamma-terpinene, beta-phellandrene
      and terpinolene, were determined in yuzu samples of the highest commercial
      quality from 42 different production districts. Statistical treatment of these
      data by the t-test and sign test revealed significant differences of the isotope
      effects in each yuzu sample. It is suggested that this technique will be
      applicable for evaluating the quality, genuineness and origin of citrus fruits
      and their products. The isotope fingerprints were also demonstrated in several
      citrus fruits other than the yuzu samples.

PMID- 11826957
TI  - Synthesis of southern (C1'-C11') and eastern (C8-C18) fragments of pamamycin-607,
      an aerial mycelium-inducing substance of Streptomyces alboniger.
AB  - Synthesis of the southern C1'-C11' and eastern C8-C18 fragments of pamamycin-607,
      an aerial mycelium-inducing substance of Streptomyces alboniger, was achieved.
      The southern fragment was synthesized by using the Evans aldol reaction and cis
      selective iodoetherification as the key steps in a 9.6% overall yield (7 steps).
      The eastern fragment was constructed via the Julia coupling reaction and cis
      selective iodoetherification in a 3.0% overall yield (8 steps from the known
      epoxide).

PMID- 11826958
TI  - Steric effects on interaction of tea catechins with lipid bilayers.
AB  - Interaction of tea catechins with lipid bilayers has been investigated with
      liposome systems. Tea catechins are classified into cis-type and trans-type from
      the configuration of the two hydrogens at the 2 and 3 positions on the C-ring.
      The amount of trans-type catechins incorporated into liposomes was less than that
      of the respective cis-type catechins. Furthermore, the order of the partition
      coefficients of catechins in an n-octanol/PBS system is the same as that of the
      amount incorporated into liposomes. These results indicate that in addition to
      the number of hydroxyl groups on the B-ring and the presence of the galloyl
      moiety, the stereochemical structure of the C-ring also governs the
      hydrophobicity and the affinity for lipid bilayers. Trans-type catechins with the
      galloyl moiety were located on the surface of the lipid bilayer, as well as cis
      type catechins with the galloyl moiety, and perturbed the membrane structure.
      These different stereochemical structures should influence the affinity for lipid
      bilayers, the alteration of membrane structures, and the difference in the order
      of the biological activities.

PMID- 11826959
TI  - Purification and characterization of maltose phosphorylase from Bacillus sp. RK
      1.
AB  - Bacillus sp. RK-1 was isolated as a bacterium that produced maltose phosphorylase
      (MPase) in the culture supernatant. Screening was done from among about 400
      isolates that could grow at 55 degrees C in a medium containing maltose as the
      sole carbon source. The enzyme was purified to an electrophoretically homogeneous
      state and some properties were investigated. The Mr of the enzyme was estimated
      to be 170 kDa by gel filtration and 88.5 kDa by SDS-PAGE, suggesting that it
      consisted of two identical subunits. The enzyme showed optimum activity around pH
      6.0-7.0 and the optimum temperature was about 65 degrees C. The enzyme was stable
      in the range of pH 5.5-8.0 after keeping it at 4 degrees C for 24 h and retained
      the activity up to about 55 degrees C after keeping it for 15 min. This is the
      first report about an MPase that could be produced in the culture supernatant.
      Furthermore, these investigations showed that this MPase is one of the most
      thermostable ones reported so far.

PMID- 11826960
TI  - Isolation, growth, ultrastructure, and metal tolerance of the green alga,
      Chlamydomonas acidophila (Chlorophyta).
AB  - An acidophilic volvocine flagellate, Chlamydomonas acidophila (Volvocales) that
      was isolated from an acid lake, Katanuma, in Miyagi prefecture, Japan was studied
      for growth, ultrastructural characterization, and metal tolerance. Chlamydomonas
      acidophila is obligately photoautotrophic, and did not grow in the cultures
      containing acetate or citrate even in the light. The optimum pH for growth was
      3.5-4.5. To characterize metal tolerance, the toxic effects of Cd, Co, Cu, and Zn
      on this alga were also studied. Effective metal concentrations, which limited the
      growth by 50%, EC50 were measured, after 72 h of static exposure. EC50s were 14.4
      microM Cd2+, 81.3 microM Co2+, 141 microM Cu2+, and 1.16 mM Zn2+ for 72 h of
      exposure. Thus, this alga had stronger tolerance to these metals than other
      species in the genus Chlamydomonas.

PMID- 11826961
TI  - Purification and identification of the essential ionizable groups of honeybee,
      Apis mellifera L., trehalase.
AB  - Trehalase (EC 3.2.1.28) of the bound type was purified as an electrophoretically
      homogeneous protein from adult honeybees by fractionation with ammonium sulfate,
      hydrophobic chromatography, and DEAE-Sepharose CL-6B, CM-Sepharose CL-6B, butyl
      Toyopearl 650M, and p-aminophenyl beta-glucoside Sepharose 4B column
      chromatographies. The enzyme preparation was confirmed to be a monomeric protein
      containing 3.1% carbohydrate. The molecular weight was estimated to be
      approximately 69,000, and the optimum pH was 6.7. The Michaelis constant (Km) was
      0.66 mM, and the molecular activity (k0) was 86.2 s(-1). The enzyme was an
      "inverting" type which produced beta-glucose from alpha, alpha-trehalose.
      Dependence of the V and Km values on pH gave values for the ionization constants,
      pKe1 and pKe2, of essential ionizable groups 1 and 2 of the free enzyme of 5.3
      and 8.5, respectively. When the dielectric constant of the reaction mixture was
      decreased, pKe1, and pKe2 were shifted to higher values of + 0.2 and + 0.5 pH
      unit, respectively. The ionization heat (deltaH) of ionizable group 1 was
      estimated to be + 1.8 kcal/mol, and the deltaH value of group 2 was + 1.5
      kcal/mol. These findings strongly support the notion that the essential ionizable
      groups of honeybee trehalase are two kinds of carboxyl groups, one being a
      dissociated type (-COO(-), ionizable group 1) and the other a protonated type (
      COOH, ionizable group 2), although the pKe2 value is high.

PMID- 11826962
TI  - High yield synthesis of nitriles by a new enzyme, phenylacetaldoxime dehydratase,
      from Bacillus sp. strain OxB-1.
AB  - 3-Phenylpropionitrile was synthesized from Z-3-phenylpropionaldoxime (0.75 M) in
      a quantitative yield (98 g/l) by the use of cells of Escherichia coli JM 109/pOxD
      90F, a transformant harboring a gene for a new enzyme, phenylacetaldoxime
      dehydratase, from Bacillus sp. strain OxB-1. Other arylalkyl- and alkyl-nitriles
      were also synthesized in high yields from the corresponding aldoximes. Moreover,
      3-phenylpropionitrile was successfully synthesized by the recombinant cells in 70
      and 100% yields from 0.1 M unpurified E/Z-3-phenylpropionaldoxime, which is
      spontaneously formed from 3-phenylpropionaldehyde and hydroxylamine in a butyl
      acetate/water biphasic system and aqueous phase, respectively.

PMID- 11826963
TI  - Quantitative and specific detection of a trichloroethylene-degrading
      methanotroph, Methylocystis sp. strain M, by a most probable number-polymerase
      chain reaction method.
AB  - We developed a rapid and specific enumeration method for a trichloroethylene
      degrading methanotroph, Methylocystis sp. strain M, based on a most probable
      number-polymerase chain reaction method for monitoring the bacterium at
      bioremediation sites. The primers designed for the mmoC gene of the soluble
      methane monooxygenase gene cluster were specific to strain M. Recovery of the
      cells with a membrane filter enabled us to detect strain M in trichloroethylene
      contaminated groundwater. We used the enumeration method to monitor the number of
      strain M cells in effluent from soil columns supplied with trichloroethylene
      contaminated groundwater. The number of strain M cells in the effluent depended
      on the amount of the strain M inoculated and the number of cells measured by the
      most probable number-polymerase chain reaction method was correlated with that
      measured by a culture method. The detection limit for strain M in effluent
      detected by MPN-PCR method was 4 to 8 x 10(2) cells/ml.

PMID- 11826964
TI  - Mutational and comparative analysis of streptolysin O, an oxygen-labile
      streptococcal hemolysin.
AB  - The structural gene of streptolysin O was cloned from Streptococcus pyogenes
      strain Sa and S. equisimilis H46A, and the nucleotide sequences were compared
      with those of strain Richards. To obtain the minimal active fragment of the toxin
      and to elucidate structure-function relationships in hemolytic function,
      streptolysin O mutants deleted in N- and C-terminal regions were constructed.
      Internal amino acid residues were also replaced by introduction of point
      mutations. Analyses of these mutants showed that considerable activity was
      retained even after deletion of the N-terminal 107 residues, but genetic removal
      of the ultimate C-terminal residue resulted in a marked decrease in hemolytic
      function. By removal in succession, hemolytic activity declined exponentially,
      and only 0.002% of the activity remained after deletion of the C-terminal four
      residues. Nucleotide replacement experiments indicated pivotal roles of I202,
      V217, D324-L325, V339, and H469 residues in hemolysis.

PMID- 11826965
TI  - Antihypertensive effects of acetic acid and vinegar on spontaneously hypertensive
      rats.
AB  - To clarify the possibility of a preventive effect of dietary vinegar on blood
      pressure, long-term administration of vinegar or the acetic acid to SHR was
      examined. As a result, it was observed that acetic acid itself, the main
      component of vinegar, significantly reduced both blood pressure (p<0.05) and
      renin activity (p<0.01) compared to controls given no acetic acid or vinegar, as
      well as vinegar. There were no significant differences in angiotensin I
      converting enzyme activity in various organs. As for the mechanism of this
      function, it was suggested that this reduction in blood pressure may be caused by
      the significant reduction in renin activity and the subsequent decrease in
      angiotensin II. From this study, it was also suggested that the antihypertensive
      effect of vinegar is mainly due to the acetic acid in it.

PMID- 11826966
TI  - Novel substrate specificity of designer 3-isopropylmalate dehydrogenase derived
      from Thermus thermophilus HB8.
AB  - Redesigning of an enzyme for a new catalytic reaction and modified substrate
      specificity was exploited with 3-isopropylmalate dehydrogenase (IPMDH). Point
      mutation on Gly-89, which is not in the catalytic site but near it, was done by
      changing it to Ala, Ser, Val, and Pro, and all the mutations changed the
      substrate specificity. The mutant enzymes showed higher catalytic efficiency
      (kcat/Km) than the native IPMDH when malate was used as a substrate instead of 3
      isopropylmalate. More interestingly, an additional insertion of Gly between Gly
      89 and Leu-90 significantly altered the substrate-specificity, although the
      overall catalytic activity was decreased. Particularly, this mutant turned out to
      efficiently accept D-lactic acid, which was not accepted as a substrate by wild
      type IPMDH at all. These results demonstrate the opportunity for creating
      nove,enzymes by modification of amino acid residues that do not directly
      participate in catalysis, or by insertion of additional residues.

PMID- 11826967
TI  - Cloning, sequencing, and expression of the gene encoding 4-hydroxy-4-methyl-2
      oxoglutarate aldolase from Pseudomonas ochraceae NGJ1.
AB  - A DNA fragment that carried the gene (proA) encoding 4-hydroxy-4-methyl-2
      oxoglutarate aldolase was cloned from the chromosomal DNA of Pseudomonas
      ochraceae NGJ1, and the coding region was assigned to the nucleotide sequence
      based on the N-terminal amino acid sequence of the enzyme purified from the
      organism. The proA gene was 684 bp long, corresponding to a protein of 227 amino
      acid residues with a calculated molecular mass of 24,067 Da. The genes encoding a
      putative transporter and a 4-oxalomesaconate hydratase were upstream, and a 3'
      truncated gene encoding 2-pyrone-4,6-dicarboxylate lactonase was downstream from
      the proA gene in the same orientation on the DNA fragment. The proA gene product
      was overproduced in Escherichia coli and briefly purified to homogeneity from the
      crude extract by a two-step purification. The molecular and catalytic properties
      of the gene product were similar to those of the P. ochraceae enzyme.

PMID- 11826968
TI  - Localization, accumulation, and antifungal activity of chitinases in rye (Secale
      cereale) seed.
AB  - In order to understand a physiological role of chitinases in rye, the
      localization and accumulation of rye seed chitinase-a and -c (RSC-a and -c) in
      the seeds were studied by immunochemical methods. An antiserum specific to the
      chitin-binding domain (CB-domain), which is an N-terminal part of RSC-a, and an
      antiserum specific to the catalytic region of RSC-a and RSC-c were used. An
      immunoblot analysis detected both RSC-a and RSC-c in the endosperm of the rye
      seed. Immunohistochemical staining indicated that RSC-a was localized in only the
      aleurone cells, whereas RSC-c existed at least in the starchy endosperm and was
      also likely to exist in the aleurone cells. It was found by ELISA and an
      immunoblot analysis that RSC-a and -c accumulated in the seed during the later
      stage of development. Both chitinases and the Cat-domain exhibited antifungal
      activity toward Trichoderma species, while the CB-domain did not. Observation of
      the inhibition of hyphal growth of the T. species suggests that the two
      chitinases acted in different ways.

PMID- 11826969
TI  - Substrate specificity of beta-primeverosidase, a key enzyme in aroma formation
      during oolong tea and black tea manufacturing.
AB  - We synthesized nine kinds of diglycosides and a monoglycoside of 2-phenylethanol
      to investigate the substrate specificity of the purified beta-primeverosidase
      from fresh leaves of a tea cultivar (Camellia sinensis var. sinensis cv.
      Yabukita) in comparison with the apparent substrate specificity of the crude
      enzyme extract from tea leaves. The crude enzyme extract mainly showed beta
      primeverosidase activity, although monoglycosidases activity was present to some
      extent. The purified beta-primeverosidase showed very narrow substrate
      specificity with respect to the glycon moiety, and especially prominent
      specificity for the beta-primeverosyl (6-O-beta-D-xylopyranosyl-beta-D
      glucopyranosyl) moiety. The enzymes hydrolyzed naturally occurring diglycosides
      such as beta-primeveroside, beta-vicianoside, beta-acuminoside, beta
      gentiobioside and 6-O-alpha-L-arabinofuranosyl-beta-D-glucopyranoside, but were
      unable to hydrolyze synthetic unnatural diglycosides. The purified enzyme was
      inactive toward 2-phenylethyl beta-D-glucopyranoside. The enzyme hydrolyzed each
      of the diglycosides into the corresponding disaccharide and 2-phenylethanol.
      These results indicate the beta-primeverosidase, a diglycosidase, to be a key
      enzyme involved in aroma formation during the tea manufacturing process.

PMID- 11826971
TI  - Administration of capsiate, a non-pungent capsaicin analog, promotes energy
      metabolism and suppresses body fat accumulation in mice.
AB  - We investigated the effects of a single oral administration of capsiate, which is
      found in the fruits of a non-pungent cultivar of pepper, CH-19 Sweet, and has the
      same structure as capsaicin except for replacement of NH by O in the alkyl chain,
      on the thermogenesis and fat accumulation in mice. The oxygen consumption and
      serum adrenalin concentration were higher in both the capsaicin (10 mg/kg-body
      weight) and capsiate (10 mg/kg-body weight) groups than those in the control
      group. We also examined the effects of 2 weeks of administration of capsaicin and
      capsiate on body fat accumulation. Eevery day for 2 weeks administration of
      capsiate (10, 50 mg/kg-body weight/day) markedly suppressed body fat accumulation
      as well as capsaicin (10 mg/kg-body weight/day). These results suggest that
      capsiate promotes energy metabolism and suppresses body fat accumulation as does
      capsaicin.

PMID- 11826970
TI  - Sandwich enzyme-linked immunosorbent assay system for micro-detection of the
      wheat allergen, Tri a Bd 17 K.
AB  - Seven monoclonal antibodies (mAbs) against the wheat allergen, Tri a Bd 17 K,
      were prepared to obtain mAbs suitable for a sandwich enzyme-linked immunosorbent
      assay (sandwich ELISA) for determination of the allergen. Two of the mAbs
      strongly immunoblotted the allergen purified from wheat flour. However, only one
      (1G11) of them was found to be suitable for sandwich ELISA. Epitope mapping
      against mAb-1G11 on the allergen showed that the mAb recognized the peptide
      containing Lys-38 and Gln-39 of the allergen. We developed a sandwich ELISA
      method consisting of Aleuria aurantia lectin for fixing the allergen and 1G11 as
      the first antibody that enabled 4-4,000 ng/well of the allergen to be determined.

PMID- 11826972
TI  - A gene encoding phosphatidylethanolamine N-methyltransferase from Acetobacter
      aceti and some properties of its disruptant.
AB  - Phosphatidylcholine (PC) is a major component of membranes not only in
      eukaryotes, but also in several bacteria, including Acetobacter. To identify the
      PC biosynthetic pathway and its role in Acetobacter sp., we have studied
      Acetobacter aceti IFO3283, which is characterized by high ethanol oxidizing
      ability and high resistance to acetic acid. The pmt gene of A. aceti, encoding
      phosphatidylethanolamine N-methyltransferase (Pmt), which catalyzes methylation
      of phosphatidylethanolamine (PE) to PC, has been cloned and sequenced. One
      recombinant plasmid that complemented the PC biosynthesis was isolated from a
      gene library of the genomic DNA of A. aceti. The pmt gene encodes a polypeptide
      with molecular mass of either 25125, 26216, or 29052 for an about 27-kDa protein.
      The sequence of this gene showed significant similarity (44.3% identity in the
      similar sequence region) with the Rhodobacter sphaeroides pmtA gene which is
      involved in PE N-methylation. When the pmt gene was expressed in E. coli, which
      lacks PC, the Pmt activity and PC formation were clearly demonstrated. A. aceti
      strain harboring an interrupted pmt allele, pmt::Km, was constructed. The pmt
      disruption was confirmed by loss of Pmt and PC, and by Southern blot analyses.
      The null pmt mutant contained no PC, but tenfold more PE and twofold more
      phosphatidylglycerol (PG). The pmt disruptant did not show any dramatic effects
      on growth in basal medium supplemented with ethanol, but the disruption caused
      slow growth in basal medium supplemented with acetate. These results suggest that
      the lack of PC in the A. aceti membrane may be compensated by the increases of PE
      and PG by an unknown mechanism, and PC in A. aceti membrane is related to its
      acetic acid tolerance.

PMID- 11826973
TI  - (4E)-dehydrocitrals [(2E,4E)- and (2Z,4E )-3,7-dimethyl-2,4,6-octatrienals] from
      acarid mite Histiogaster sp. A096 (Acari: Acaridae).
AB  - A mixture of two monoterpenes was obtained as the opisthonotal gland secretion
      from unidentified Histiogaster sp. A096 (Acari: Acaridae), and their structures
      were elucidated to be (4E)-dehydrocitrals [(2E,4E)- and (2Z,4E)-3,7-dimethyl
      2,4,6-octatrienals] by GC/MS, GC/FT-IR, UV and 1H-NMR spectra. Both isomers of
      (4E)-dehydrocitral prepared by syntheses in 4 steps from 3-methyl-2-butenal with
      34.2% yields (based on the ylide) were separated by column chromatography into
      the (2E,4E)- and (2Z,4E)-3,7-dimethyl-2,4,6-octatrienal. Mass spectra together
      with GC retention times of the purified natural (4E)-dehydrocitrals were
      identical with those of synthetic (2E,4E)-3,7-dimethyl-2,4,6-octatrienal and
      (2Z,4E)-3,7-dimethyl-2,4,6-octatrienal. The geometry at the 2-C position of both
      synthetic (4E)-dehydrocitrals was confirmed by NOESY analyses. This is the first
      identification of (4E)-dehydrocitrals from the animal kingdom.

PMID- 11826974
TI  - Membrane-bound quinoprotein D-arabitol dehydrogenase of Gluconobacter suboxydans
      IFO 3257: a versatile enzyme for the oxidative fermentation of various ketoses.
AB  - Solubilization of membrane-bound quinoprotein D-arabitol dehydrogenase (ARDH) was
      done successfully with the membrane fraction of Gluconobacter suboxydans IFO
      3257. In enzyme solubilization and subsequent enzyme purification steps, special
      care was taken to purify ARDH as active as it was in the native membrane, after
      many disappointing trials. Selection of the best detergent, keeping ARDH as the
      holoenzyme by the addition of PQQ and Ca2+, and of a buffer system involving
      acetate buffer supplemented with Ca2+, were essential to treat the highly
      hydrophobic and thus labile enzyme. Purification of the enzyme was done by two
      steps of column chromatography on DEAE-Toyopearl and CM-Toyopearl in the presence
      of detergent and Ca2+. ARDH was homogenous and showed a single sedimentation peak
      in analytical ultracentrifugation. ARDH was dissociated into two different
      subunits upon SDS-PAGE with molecular masses of 82 kDa (subunit I) and 14 kDa
      (subunit II), forming a heterodimeric structure. ARDH was proven to be a
      quinoprotein by detecting a liberated PQQ from SDS-treated ARDH in HPLC
      chromatography. More preliminarily, an EDTA-treated membrane fraction lost the
      enzyme activity and ARDH activity was restored to the original level by the
      addition of PQQ and Ca2+. The most predominant unique character of ARDH, the
      substrate specificity, was highly versatile and many kinds of substrates were
      oxidized irreversibly by ARDH, not only pentitols but also other polyhydroxy
      alcohols including D-sorbitol, D-mannitol, glycerol, meso-erythritol, and 2,3
      butanediol. ARDH may have its primary function in the oxidative fermentation of
      ketose production by acetic acid bacteria. ARDH contained no heme component,
      unlike the type II or type III quinoprotein alcohol dehydrogenase (ADH) and did
      not react with primary alcohols.

PMID- 11826975
TI  - Purification and characterization of membrane-bound quinoprotein cyclic alcohol
      dehydrogenase from Gluconobacter frateurii CHM 9.
AB  - A quinoprotein catalyzing oxidation of cyclic alcohols was found in the membrane
      fraction for the first time, after extensive screening among aerobic bacteria.
      Gluconobacter frateurii CHM 9 was finally selected in this study. The enzyme
      tentatively named membrane-bound cyclic alcohol dehydrogenase (MCAD) was found to
      occur specifically in the membrane fraction, and pyrroloquinoline quinone (PQQ)
      was functional as the primary coenzyme in the enzyme activity. MCAD catalyzed
      only oxidation reaction of cyclic alcohols irreversibly to corresponding ketones.
      Unlike already known cytosolic NAD(P)H-dependent alcohol-aldehyde or alcohol
      ketone oxidoreductases, MCAD was unable to catalyze the reverse reaction of
      cyclic ketones or aldehydes to cyclic alcohols. MCAD was solubilized and purified
      from the membrane fraction of the organism to homogeneity. Differential
      solubilization to eliminate the predominant quinoprotein alcohol dehydrogenase
      (ADH), and the subsequent two steps of column chromatographies, brought MCAD to
      homogeneity. Purified MCAD had a molecular mass of 83 kDa by SDS-PAGE. Substrate
      specificity showed that MCAD was an enzyme oxidizing a wide variety of cyclic
      alcohols. Some minor enzyme activity was found with aliphatic secondary alcohols
      and sugar alcohols, but not primary alcohols, differentiating MCAD from
      quinoprotein ADH. NAD-dependent cytosolic cyclic alcohol dehydrogenase (CCAD) in
      the same organism was crystallized and its catalytic and physicochemical
      properties were characterized. Judging from the catalytic properties of CCAD, it
      was apparent that CCAD was distinct from MCAD in many respects and seemed to make
      no contributions to cyclic alcohol oxidation.

PMID- 11826976
TI  - Improvement of the electro-transformation efficiency of facultatively
      alkaliphilic Bacillus pseudofirmus OF4 by high osmolarity and glycine treatment.
AB  - An electro-transformation method was established for facultatively alkaliphilic
      Bacillus pseudofirmus OF4. A high osmolarity electroporation medium with a high
      electric field strength was effective. Transformation efficiency improved 110
      fold in glycine-treated cells compared to non-glycine-treated cells. Under
      optimum conditions, the transformation efficiency was 1.69 x 10(6) transformants
      per microg of pUB110.

PMID- 11826977
TI  - Factors in bovine colostrum that enhance the migration of human fibroblasts in
      type I collagen gels.
AB  - Bovine colostrum has an activity that increases the migration of WI38
      fibroblasts. We evaluated the motility of fibroblasts by their ability to
      contract collagen gels. Part of the activity was absorbed by anion-exchange
      chromatography at pH 6.4, and eluted by 0.2-0.3 M sodium chloride. The activity
      was separated into many fractions corresponding to 20-150 kDa by gel filtration
      chromatography under acidic conditions. The major peak of the activity coincided
      with 50-70 kDa.

PMID- 11826978
TI  - Analysis of the molecular species of hydrogenase in the cells of an obligately
      chemolithoautotrophic, marine hydrogen-oxidizing bacterium, Hydrogenovibrio
      marinus.
AB  - Hydrogenovibrio marinus was suggested to have only membrane-bound hydrogenase
      (MBH). The change of cultivation pO2 did not affect the molecular species of
      hydrogenase expressed. We propose the MBH is grouped in class I [NiFe] MBH
      according to the subunit composition, size (Mw 38,000 and Mw 74,000 subunits) and
      N-terminal sequences of the subunits, and arrangement of the structural genes. Ni
      requirement for the autotrophic growth on H2 also suggested the MBH is the Ni
      containing type. Southern hybridization analysis using a part of the MBH gene
      showed a possibility of the presence of two highly homologous MBHs which were not
      separated by SDS-PAGE.

PMID- 11826979
TI  - Isolation and primary structural analysis of two conjugated polyketone reductases
      from Candida parapsilosis.
AB  - Two conjugated polyketone reductases (CPRs) were isolated from Candida
      parapsilosis IFO 0708. The primary structures of CPRs (C1 and C2) were analyzed
      by amino acid sequencing. The amino acid sequences of both enzymes had high
      similarity to those of several proteins of the aldo-keto-reductase (AKR)
      superfamily. However, several amino acid residues in the putative active sites of
      AKRs were not conserved in CPRs-C1 and -C2.

PMID- 11826980
TI  - Molecular cloning and characterization of cotton cDNAs expressed in developing
      fiber cells.
AB  - Using the FDD-PCR technique, ten new fiber-specific cDNAs were isolated from
      developing cotton fiber cells and showed high amino acid identity to previously
      recorded cDNAs. Five cDNAs encoding bisphosphate nucleotidase, alpha-tubulin,
      beta-galactosidase, annexin, and reversibly glycosylated polypeptide were
      identified while the functions of five other cDNAs were undetermined. Dot blot
      analysis showed that all transcripts of the 10 cDNAs accumulated preferentially
      in fiber cells and the majority were expressed in the early phase of cotton fiber
      development, except for F14 which accumulated at a high level during the late
      phase of developing fiber cells, indicating that all of the genes were involved
      in the process of fiber development.

PMID- 11826981
TI  - Analysis of upstream region of nicotianamine synthase gene from Arabidopsis
      thaliana: presence of putative ERE-like sequence.
AB  - Nicotianamine (NA) is present in all plants so far examined, and is thought to
      chelate transition metal ions. Previously, we isolated three nicotianamine
      synthase (NAS) genes of Arabidopsis thaliana (AtNAS1, 2, and 3) and showed that
      each NAS gene is differentially expressed. Deletion analysis of the 5' flanking
      region of AtNAS3 found a putative ethylene-responsive sequence, ATTTTCAAA.

PMID- 11826982
TI  - Human tyrosine tRNA is also internally cleavable by E. coli ribonuclease P RNA
      ribozyme in vitro.
AB  - Transfer RNA is an essential molecule for biological system, and each tRNA
      molecule commonly has a cloverleaf structure. Previously, we experimentally
      showed that some Drosophila tRNA (tRNA(Ala), tRNA(His), and tRNA(iMet)) molecules
      fit to form another, non-cloverleaf, structure in which the 3'-half of the tRNA
      molecules forms an alternative hairpin, and that the tRNA molecules are
      internally cleaved by the catalytic RNA of bacterial ribonuclease P (RNase P).
      Until now, the hyperprocessing reaction of tRNA has only been reported with
      Drosophila tRNAs. This time, we applied the hyperprocessing reaction to one of
      human tRNAs, human tyrosine tRNA, and we showed that this tRNA was also
      hyperprocessed by E. coli RNase P RNA. This tRNA is the first example for
      hyperprocessed non-Drosophila tRNAs. The results suggest that the hyperprocessing
      reaction can be a useful tool detect destablized tRNA molecules from any species.

PMID- 11826983
TI  - Purification of an aminopeptidase preferentially releasing N-terminal alanine
      from cucumber leaves and its identification as a plant aminopeptidase N.
AB  - In this study, a highly active foliar aminopeptidase preferentially releasing N
      terminal alanine from artificial substrates was purified and characterized from
      cucumber (Cucumis sativus L. suyo). The enzyme had a molecular mass of 200 kDa
      consisting of two subunits of 95 kDa. It was a metalloprotease the pH optimum of
      which was 8 to 9. It cleaved Ala-, Gly-, Met-, Ser-, Leu-, Lys-, and Arg
      artificial substrates. An internal amino acid sequence was similar to those of
      aminopeptidase N (clan MA, family M1) of microorganisms, and was very similar to
      that of a putative aminopeptidase N of Arabidopsis thaliana. From these results,
      the highly active aminopeptidase in cucumber leaves was identified to be a plant
      aminopepitdase N.

PMID- 11826985
TI  - Questioning questionnaires.

PMID- 11826984
TI  - Functional similarities of recombinant OLP and cytokinin-binding protein 2.
AB  - CBP1 and CBP2 are cytokinin-binding proteins isolated from tobacco callus. In
      particularly, CBP2 is a 26-kDa protein with high affinity (Kd=1.08 x 10(-6) M)
      for cytokinin [Kobayashi et al. Plant Cell Physiol.41(2): 148-157 (2000)] and the
      N-terminal amino acid analysis of CBP2 showed high sequence homology (92.9%) to
      tobacco osmotin-like protein (OLP). To compare the properties of OLP and CBP2,
      recombinant OLP was purified, and binding to benzyladenine (BA) was examined. The
      inclusion bodies of recombinant OLP were solubilized in 8 M urea and purified on
      an SP-Sepharose column. SDS-PAGE analysis of the purified recombinant OLP
      revealed a single band of 26 kDa. The Kd of solublized recombinant OLP to BA
      obtained from a Scatchard plot was 1.10 x 10(-6) M, which was similar to the Kd
      of CBP2 to BA (1.08 x 10(-6) M).

PMID- 11826986
TI  - The potential of marrow stromal cells in stem cell therapy.

PMID- 11826987
TI  - UK survey of attitudes to local anaesthesia for vitreoretinal surgery.
AB  - BACKGROUND: The use of local anaesthesia (LA) for vitreoretinal (VR) surgery is
      growing although surgeons in the UK traditionally use general anaesthesia.
      PURPOSE: To assess the use and attitudes towards local anaesthesia for VR surgery
      among the members of the British and Eire Association of Vitreo-retinal Surgeons
      (BEAVRS). METHODS: A questionnaire was sent to members of BEAVRS. Use of LA was
      assessed for the following procedures: macular hole; diabetic vitrectomy;
      vitrectomy; cryopexy and gas; buckling and re-buckling procedures. Attitudes of
      surgeons generally using LA for primary retinal detachment surgery (> 50% of
      cases) were compared with those generally using general anaesthesia (GA) (> 50%
      of cases). RESULTS: 33.6% of surgeons preferred LA for macular hole; 26.2% for
      diabetic vitrectomy; 23.3% for vitrectomy, cryopexy and gas; 21.4% for buckling
      procedures; and 9.35% for re-buckling procedures. When surgeons routinely using
      LA were compared with those regularly using GA they considered LA less stressful
      for patients and surgeon, patients tolerant to longer operations, and buckling or
      redo surgery no more difficult under LA. However, both groups considered surgery
      on young patients and teaching relatively more difficult under LA. CONCLUSION:
      The use of LA may convey benefits for VR surgery and faster rehabilitation for
      patients. However, we identified wide variations in the use of and attitudes to
      LA for VR surgery in British surgeons.

PMID- 11826988
TI  - Frequency-doubled Nd:YAG laser for the treatment of exudative diabetic
      maculopathy.
AB  - PURPOSE: To determine the clinical efficacy of frequency-doubled Nd:YAG (FD YAG)
      laser for the treatment of diabetic clinically significant macular oedema (CSMO).
      METHODS: A prospective pilot study was carried out on 55 eyes with CSMO. FD YAG
      laser exposures were applied in a focal or grid pattern. The results were
      evaluated by Snellen visual acuity, slit-lamp biomicroscopy, colour photography
      and fundus fluorescein angiography. RESULTS: At mean review of 5.3 months,
      macular oedema had resolved either completely or partly in 44 (80%) eyes, was
      unchanged in 10 (18%) eyes and progressed in 1 (2%) eye. Visual acuity improved
      in 11 (20%), stabilised in 40 (73%) and deteriorated in 4 (7%) eyes. CONCLUSION:
      FD YAG laser therapy is effective in the treatment of CSMO. It combines the
      ergonomic advantages of a solid-state laser with the benefits of its wavelength.
      A comparison between the clinical results of FD YAG and other lasers used in the
      treatment of CSMO is, however, required.

PMID- 11826989
TI  - Co-morbidity in patients with sight-threatening diabetic retinopathy.
AB  - PURPOSE: To describe the level of co-morbidity in patients with sight-threatening
      diabetic retinopathy in the United Kingdom. METHODS: Questionnaires were
      completed by patients undergoing first photocoagulation treatment for diabetic
      maculopathy or proliferative retinopathy during a 2 month period throughout the
      UK. RESULTS: Overall 15% of patients described angina, 9% had suffered a
      myocardial infarction and 6% a stroke. Self-reported renal disease was present in
      8.5%. Foot ulceration was described by 10% of patients, and 4% had undergone an
      amputation. 35.5% of patients were on treatment for hypertension. 17.5% of
      patients had been hospitalised in the previous 6 months, and 3% of patients had
      died within 9 months of the laser treatment. CONCLUSIONS: There was significant
      co-morbidity in these patients, which may affect the management of their
      retinopathy.

PMID- 11826990
TI  - A nationwide survey of post-operative instructions following uncomplicated
      phacoemulsification cataract surgery.
AB  - PURPOSE: To determine the heterogeneity of post-operative instructions following
      uncomplicated phacoemulsification cataract surgery. METHODS: A survey was sent to
      a random sample of 115 cataract centres in the United Kingdom. Eighty
      questionnaires were returned, corresponding to a response rate of 70%. RESULTS:
      The time at which post-operative advice was given, the nature of post-operative
      problems, and advice regarding the instillation of post-operative eye drops were
      all very similar among centres. There was mild variability among centres in the
      advice given on post-operative analgesia, eye cleaning and hair washing. However,
      there were marked differences in the advice given to patients regarding how long
      an eyeshield should be worn, and also regarding daily activities such as lifting
      objects and driving. Thirty-five per cent of centres adopted a single post
      operative review. No centre had more than three post-operative reviews for an
      uncomplicated phacoemulsification. The final refraction was conducted by at least
      30% of centres within the first month, and by at least 92% within 2 months.
      CONCLUSIONS: Phacoemulsification with a self-sealing tunnel is now the technique
      of choice for an uncomplicated cataract extraction and is increasingly conducted
      on a daycase basis. However, our survey reveals that there is considerable
      heterogeneity in the postoperative instructions given to patients following this
      procedure, and we would suggest that considerable benefits would result from
      further work in this area. Standard guidelines would not only benefit the patient
      in terms of improved patient education and rehabilitation, but would also result
      in economic benefits from reduced post-operative visits.

PMID- 11826991
TI  - Errors leading to unexpected pseudophakic ametropia.
AB  - PURPOSE: Determination of the reasons for clinically significant unplanned
      ametropia following cataract surgery and the results of management of the
      ametropia. METHODS: Retrospective review of 11 consecutive cases of tertiary
      referral for management of pseudophakic ametropia to the authors. Corrective
      surgery involved either lens implant exchange or LASIK refractive surgery. Final
      outcome was assessed by uncorrected and best spectacle corrected visual acuity
      and manifest refractive outcome. RESULTS: Five cases (45%) were due to
      significant error in axial length determination at pre-surgery biometry. Six
      cases (55%) were due to surgeon or surgical team error, where the surgeon
      implanted a lens of power at variance with that specified pre-operatively. Nine
      patients elected to undergo refractive surgery to correct the ametropia and 2
      elected to wear a spectacle lens. Seven underwent lens implant exchange and 2
      patients underwent LASIK keratorefractive surgery. Eight of nine patients were
      within 1 dioptre of intended spherical equivalent after refractive surgery and 1
      patients was -1.5 dioptre myopic. CONCLUSIONS: Most cases of serious unintended
      ametropia after cataract surgery are avoidable. Care should be taken with the
      biometry and procedural checks to minimise error. When lens implant exchange or
      LASIK was performed the final refractive results were satisfactory.

PMID- 11826992
TI  - The effect of sub-Tenon's anaesthesia on intraocular pressure.
AB  - PURPOSE: To assess the effect of sub-Tenon's anaesthesia on intraocular pressure
      (IOP) prior to cataract surgery. METHODS: Fifty consecutive patients undergoing
      phacoemulsification of cataract were recruited. Routine sub-Tenon's anaesthesia
      was administered with 5 ml unpreserved 2% lignocaine. IOPs were measured
      immediately prior to and at 1, 3, 5 and 10 min after injection. Efficacy was
      assessed subjectively by the operating surgeon. No ocular compression was used.
      Pre- and post-injection IOPs were compared using the Wilcoxon signed rank test,
      whereas all other results were compared with baseline using Student's two-tailed
      paired t-tests. RESULTS: All patients achieved good analgesia and akinesis. There
      was no significant difference between the IOP prior to and 1 min after injection.
      At all time intervals after 3 min there was a significant reduction in IOP
      compared with the pre-injection measurement. At 5 min, the mean IOP reduction was
      2.72 mmHg and at 10 min IOP was lowered by 2.92 mmHg. Both reductions were
      statistically significant compared with baseline. CONCLUSIONS: Sub-Tenon's
      anaesthesia does not cause any significant rise in IOP, thereby possibly making
      it the anaesthetic technique of choice when an increase in IOP is undesirable.
      There is no indication for the use of an ocular pressure-reducing device when sub
      Tenon's anaesthesia is employed.

PMID- 11826993
TI  - Combined strabismus and phacoemulsification cataract surgery: a useful option in
      selected patients.
AB  - PURPOSE: To evaluate the role of combined strabismus and phacoemulsification
      cataract extraction in patients with symptomatic cataract and strabismus.
      METHODS: Four procedures of combined strabismus and cataract surgery are
      described in 3 elderly patients with strabismus of differing aetiologies. Two
      patients underwent one procedure; the other patient underwent two combined
      procedures, one to each eye. RESULTS: The visual acuity improved in all 3
      patients. Post-operative alignment of the visual axis was achieved which allowed
      resolution of symptomatic diplopia in patient 1, functional binocular single
      vision in patient 2 and a noticeably reduced compensatory head posture in patient
      3. CONCLUSIONS: Combined strabismus and cataract surgery is a safe procedure that
      can optimise visual alignment and improve visual acuity with a minimum number of
      operations.

PMID- 11826994
TI  - Vision-related quality of life impairment in an elderly UK population:
      associations with age, sex, social class and material deprivation.
AB  - PURPOSE: To describe the prevalence of vision-related quality of life (VR-QOL)
      impairment in an elderly UK population sample. METHOD: The survey, using the VCM1
      questionnaire, was based on an age- and sex-stratified random population sample
      of 2783 individuals aged 55 years or over. RESULTS: One thousand eight hundred
      and forty-six (69.7%) of 2647 eligible subjects responded. One thousand six
      hundred and eighty-three individuals completed all 10 VCM1 items. Overall the
      prevalence of a VCM1 score >2.0 ('more than a little' concern about vision) was
      4.6% (95% CI = 3.7% to 5.7%), leading to an estimate of more than 550,000
      individuals in England with substantial VR-QOL impairment. The prevalence
      increased with age from 2.1% in the 55-64 year age group to 17.9% in the group
      aged 85 years and older. The prevalence also increased as social class became
      lower, from 0 in social class I to 10.2% in social class V, and increased with
      increasing material deprivation, from 1.2% in the most affluent quintile to 6.8%
      in the most deprived quintile. Multivariable logistic regression analysis showed
      that age (p = 0.0001), decreasing social class (p = 0.03) and increasing material
      deprivation (p = 0.008) were independently associated with VR-QOL impairment
      (VCM1 score >2.0), whilst gender and means of questionnaire administration were
      not associated with VR-QOL impairment at the 5% level. CONCLUSIONS: The findings
      suggest a substantial national prevalence of VR-QOL impairment, and are
      consistent with earlier studies linking ocular disease with social deprivation.
      Consideration should be given to directing resources more carefully towards
      groups at higher risk of VR-QOL impairment, in particular the very elderly and
      socially deprived.

PMID- 11826995
TI  - The population requirement for cataract extraction: a cross-sectional study.
AB  - PURPOSE: To examine the distribution in the population of indications for
      cataract extraction in order to relate demand for this procedure to the capacity
      for satisfying it. METHODS: An age-stratified random population sample of 2783
      individuals aged 55 years and over was taken from inner-city, urban and rural
      areas of Avon and Somerset. The requirement for cataract extraction was estimated
      on the basis of measures of vision-related quality of life, refracted visual
      acuity, and application of the Oxford Clinical Cataract Classification and
      Grading System. Data were also collected concerning suitability for surgery,
      including relative contraindications to surgery and whether participants
      considered their eyesight bad enough to merit surgery. Three sets of composite
      indications were defined. RESULTS: Estimated prevalent requirements for cataract
      extraction for the three sets of composite criteria were: 29 per 1000 aged over
      55 years (95% CI 20-41) for the most inclusive criterion; 17 per thousand (95% CI
      10-27) for the intermediate criterion; and 7 per thousand (95% CI 3-14) for the
      most stringent criterion. These rates are equivalent to a national prevalent
      requirement for England of 384,000 for the most inclusive criterion. If the
      approximately 15% of individuals whose desire or fitness for surgery was
      questionable are removed from this estimate, the prevalent requirement, including
      the backlog from previous unsatisfied demand, becomes 325,000 individuals.
      CONCLUSIONS: The findings suggest only a modest imbalance between supply and
      demand for cataract surgery. In particular there was a very small prevalence of
      untreated severe cataract, less than the annual health service surgical capacity,
      suggesting that the current National Health Service surgical capacity is adequate
      for cases of severe cataract.

PMID- 11826996
TI  - Low frequency of bacteraemia during eye surgery obviates the need for
      endocarditis prophylaxis.
AB  - PURPOSE: To determine the incidence of bacteraemia following eye surgery, and
      thereby evaluate the need for antibiotic cover during such procedures, in
      patients who are at risk for bacterial endocarditis. METHODS: This prospective
      study involved 50 consecutive patients undergoing extraocular surgery at the
      Sultan Qaboos University Hospital, Muscat, Oman. Local preparation of the
      surgical site in all patients included pre-operative instillation of 0.3%
      gentamicin and 3% povidone-iodine eye drops. Two eye swabs (one from the
      conjunctival sac and another from the eyelid margin) and two venous blood samples
      (one taken just before the procedure and the second 10 min into it) were
      collected and cultured for aerobic and anaerobic bacteria. Surgery-related
      bacteraemia was defined as a negative pre-operative blood culture followed by a
      positive intraoperative blood culture of the same bacterium identified in the
      positive eye swab. RESULTS: Only two patients (4%) demonstrated surgery-related
      bacteraemia: one caused by Staphylococcus epidermidis (following entropion
      correction) and the other by Haemophilus influenzae (following
      dacryocystorhinostomy). Four other patients had positive conjunctival swabs
      without bacteraemia, the causative organisms being Haemophilus influenzae in two,
      and Staphyloccus aureus and Klebsiella pneumoniae in one each. CONCLUSION:
      Ophthalmic surgery is not associated with significant bacteraemia, and therefore
      does not mandate routine antibiotic cover in patients at risk for bacterial
      endocarditis. Stringent pre-operative preparation of the surgical site may
      suffice to minimise bacteraemia; however, this requires further study.

PMID- 11826997
TI  - Intraocular pressure and gonioscopic findings in rural communities mesoendemic
      and nonendemic for onchoceriasis, Kaduna State, Nigeria.
AB  - PURPOSE: To report on glaucoma-related ocular parameters, namely intraocular
      pressure and peripheral anterior synechiae, in the presence of onchocercal
      infection. METHODS: Two computer-generated random samples of individuals were
      drawn from communities mesoendemic and nonendemic for onchocerciasis
      respectively. Applanation tonometry and gonioscopy were carried out on these
      individuals. RESULTS: Four hundred and thirty-six and 319 individuals from the
      mesoendemic and nonendemic communities were examined respectively. The mean
      intraocular pressure was 1.58 mmHg lower in the individuals from the mesoendemic
      communities compared with those from the nonendemic communities (p < 0.001)
      despite the prevalence of peripheral anterior synechiae being higher in the
      mesoendemic communities. In these communities, there was strong evidence that the
      prevalence of peripheral anterior synechiae increased with increasing
      microfilarial load. CONCLUSIONS: Onchocercal infection produces a low-grade
      inflammatory process, which may result in a lowering of intraocular pressure
      despite the formation of peripheral anterior synechiae. Glaucomatous optic nerve
      damage may therefore not be the primary cause of visual loss in ocular
      onchocerciasis as this occurs late and is probably preceded by other blinding
      onchocercal pathology.

PMID- 11826998
TI  - Enucleation in a tertiary eye care centre in India: prevalence, current
      indications and clinicopathological correlation.
AB  - PURPOSE: Enucleation is a standard surgical treatment modality for many end-stage
      eye diseases. Indications for enucleation vary with changing trends in disease
      management. Few studies have addressed the issue of the frequency and indications
      of enucleation of eyes in India. We aimed to determine the frequency and the
      current clinical indications for enucleation in patients at a tertiary eye care
      centre in India, and attempted a clinicopathological correlation. METHODS:
      Medical records of patients undergoing enucleation at a tertiary eye care centre
      over a period of 3 1/2 years (January 1995 to July 1998) were reviewed to obtain
      patients' demographic data and socio-economic status. The clinical indications
      and predisposing factors were assessed. The formalin-fixed, paraffin-embedded
      sections of all enucleated eyes were re-evaluated and histopathological findings
      were correlated with the clinical diagnosis. The prevalence of enucleation was
      calculated, and age adjustments were done using the Indian population data from
      1998 mid-year statistics. RESULTS: Enucleation of the eye was performed in 150
      patients (151 eyes) out of 88,991 new ophthalmic cases, constituting 0.17% of the
      cases seen in the hospital, and amounting to a prevalence of 0.33% (95% CI, 0.27
      0.40). Males outnumbered females in a ratio of 1.85:1 (98 males, 53 females). The
      median age was 8 years (mean 16.8 +/- 18.3 years). Children below 15 years of age
      constituted 85.2% (95% CI, 81.2-89.21%) of cases that underwent enucleation.
      Clinical indications for enucleation included tumours in 74 (49%); staphyloma in
      38 (25%); acute injury in 20 (13%); absolute glaucoma in 9 (6%); painful blind
      eye in 5 (3%); phthisis bulbi in 1 (1%); and others in 4 (3%). Of the 74 cases
      with a clinical diagnosis of tumour, histopathology revealed retinoblastoma in 55
      (74%) cases, melanoma in 6 (8%) and ocular surface tumours in 4 (6%). Clinico
      pathological correlation was 100% in cases with a definite clinical diagnosis of
      retinoblastoma and melanoma. Nine blind eyes (6%) in which an intraocular tumour
      was one of the differential diagnoses, were negative for a tumour on
      histopathology. Staphyloma was more prevalent in the low socio-economic group (p
      = 0.0004), with a history of childhood trauma in 34% cases. CONCLUSIONS: The
      prevalence of enucleation in the population reporting to this tertiary eye care
      centre was 33 per 10,000 population over the study period of 3 1/2 years. Major
      indications for enucleation were tumours, staphyloma and trauma (88% of all
      cases). Increased frequency in the young was due to the high proportion of
      retinoblastoma and staphyloma. Childhood trauma, inflammation and malnutrition
      may together play a role in the pathogenesis of staphyloma. Awareness at the
      level of primary health care providers, paediatricians and general practitioners
      should be promoted to identify the disease process at an early stage and
      facilitate early intervention measures that could result in eye and vision
      salvage.

PMID- 11826999
TI  - Corneal shape change during accommodation.
AB  - PURPOSE: To investigate whether accommodation induces any changes in central
      corneal curvature. METHODS: Shape changes were measured on 14 subjects using a
      keratometer modified to enable a change in focus to occur without a change in
      vergence. All subjects were emmetropic and their ages ranged from approximately
      20 to 28 years. RESULTS: In 11 of the 14 subjects a difference in central corneal
      curvature, of around 0.4 D in at least one principal meridian, was found when
      focus was changed between distant and near targets. In 9 subjects the curvature
      was greater for near focus in at least one meridian. In 5 subjects the change in
      one meridian was opposite in effect to what would be expected, i.e. the curvature
      was greater at distance than at near. CONCLUSION: The study suggests that
      accommodation may have some effect on corneal shape.

PMID- 11827000
TI  - Outcomes of anterior levator resection in congenital blepharoptosis.
AB  - PURPOSE: To identify any consistent factors which may predict over- or
      undercorrection of congenital blepharoptosis treated by anterior levator
      resection. METHODS: A retrospective case note review of 100 consecutive patients
      undergoing anterior levator resection for congenital blepharoptosis was performed
      to identify: (1) the amount of ptosis and degree of levator function present pre
      operatively and (2) the surgical outcome. For unilateral ptosis, a successful
      result was defined as a lid level within 1 mm of the fellow lid following a
      single operation. RESULTS: Seventy-six per cent of all unilateral cases had a
      successful outcome at 6 weeks following surgery, falling slightly to 74% by 6
      months. The most common complications at 6 months were undercorrection (19%) and
      overcorrection (7%). All patients undercorrected at 6 months had a pre-operative
      levator function in the range of 4-10 mm with a mean of 6.4 mm, whereas all those
      overcorrected at 6 months had a levator function in the range 9-15 mm with a mean
      of 12.2 mm. In the whole population, the degree of levator function was a
      predictor of increased risk of overcorrection, with a trend towards predicting
      undercorrection as well. CONCLUSIONS: In this series of patients, pre-operative
      levator function was found to be the most significant predictor of surgical
      outcome for anterior levator resection.

PMID- 11827001
TI  - Orbital involvement in sickle cell disease: a report of five cases and review
      literature.
AB  - PURPOSE: To present five cases of orbital infarction in sickle cell disease and
      review relevant literature. METHOD: We reviewed the hospital records of 5
      patients with sickle cell disease who developed a periorbital swelling during a
      vaso-occlusive crisis and were managed at our hospital between April 1992 and
      June 2000. RESULTS: The 5 patients (4 with homozygous sickle cell disease and 1
      with sickle cell-beta-thalassaemia disease) were aged 6-15 years with a history
      of multiple admissions for vaso-occlusive crises. The periorbital swelling spread
      to the orbit in 4 cases and resulted in proptosis (2 cases), restriction of
      ocular motility and visual impairment. In all 4 cases, computed tomography and/or
      magnetic resonance imaging of the orbits showed a mass adjacent to the orbital
      wall. In 2 cases the mass was identified as a haematoma. Orbital wall infarction
      was demonstrated in 3 cases by bone/bone marrow scintigraphy. Epidural haematomas
      were detected by computed tomography in one case. All patients received
      intravenous fluids, analgesics, broad spectrum antibiotics and steroids, as well
      as simple or exchange transfusion, and responded well to medical management.
      CONCLUSIONS: Infarction of orbital bones during vaso-occlusive crises in sickle
      cell disease presents acutely with a rapidly progressive periorbital swelling.
      Haematomas frequently complicate the condition and, along with the inflammatory
      swelling, may lead to orbital compression syndrome. The condition is therefore
      sight-threatening, and necessitates prompt diagnosis and appropriate management
      for resolution without adverse sequelae. Imaging techniques are invaluable in the
      evaluation of patients. The majority of cases resolve with conservative treatment
      that includes steps to combat the vaso-occlusive crisis and use of systemic
      steroids under antibiotic cover.

PMID- 11827003
TI  - Scanning electron microscopic study of a Ciloxan bottle blocked by ciprofloxacin
      crystals.
AB  - PURPOSE: To report blockage of a commercially available ciprofloxacin bottle by
      white crystalline deposits. This study evaluated the ultrastructural features of
      the ciprofloxacin crystals. METHODS: A patient underwent intensive topical
      treatment of an infectious corneal ulcer with commercially available
      ciprofloxacin 0.3% ophthalmic solution. During treatment, the patient was unable
      to obtain medication from the ciprofloxacin bottle and required a new
      prescription. Examination of the bottle revealed that about 50% of the medication
      remained, but compression of the bottle with any amount of force failed to
      deliver any medication. On closer examination, a white material partially filled
      the nozzle track of the bottle and was on the outer bottle near the nozzle and
      the inner surface of the bottle cap. These white crystalline deposits were
      evaluated by scanning electron microscopy. RESULTS: Plate-like, needle, cable and
      spaghetti-like crystals were found. The needle crystals formed multiple petaloid
      patterns. CONCLUSIONS: This is the first report of blockage of a commercially
      available ciprofloxacin 0.3% bottle by ciprofloxacin crystals and the inability
      to deliver medication from the bottle. Ultrastructural study of the white
      crystalline deposits revealed four types of ciprofloxacin crystals.

PMID- 11827002
TI  - Endothelin-1 increase in aqueous humour caused by frequency-doubled Nd:YAG laser
      trabeculoplasty in rabbits.
AB  - PURPOSE: To study the effect of Nd:YAG laser trabeculoplasty (LT) on endothelin-1
      (ET-1) concentration of aqueous humour and intraocular pressure (IOP) in rabbits.
      METHODS: One eye of each of 18 pigmented rabbits was subjected to 360 degrees LT
      with a frequency-doubled Nd:YAG laser (532 nm), and IOP was measured with a Tono
      Pen tonometer before treatment. Post-LT IOP measurements followed by aqueous
      humour aspiration were performed under general anaesthesia at 3 and 12 h and 1, 3
      and 7 days after the treatment. The concentration of ET-1 in aqueous humour was
      measured by means of a radioimmunoassay. RESULTS: In the eyes that had undergone
      LT, the concentrations of ET-1 in the aqueous humour were significantly increased
      at 3, 12 and 24 h after the treatment compared with the contralateral eyes. ET-1
      concentrations at 3 and 7 days after LT, however, did not differ significantly
      from the corresponding contralateral control values. IOP increased following the
      treatment at 3 and 12 h. IOP values were significantly lower in the treated eyes
      at 1, 3 and 7 days after the treatment than in the control eyes. CONCLUSIONS: The
      results show that LT in rabbits was followed by an immediate and short-term
      increase in aqueous humour ET-1 that might be caused by leakage from uveal
      tissue. This may be responsible for the release of prostaglandins causing the IOP
      increase and inflammatory complications of LT.

PMID- 11827004
TI  - Irreversible neurotoxicity with acyclovir treatment of acute retinal necrosis.

PMID- 11827005
TI  - Ptois as presenting sign of metastatic skin melanoma.

PMID- 11827006
TI  - Acquired ocular toxoplasmosis in an elderly patient.

PMID- 11827008
TI  - Choroidal effusion after YAG laser capsulotomy.

PMID- 11827007
TI  - Severe bilateral panuveitis in a patient with asymptomatic Epstein-Barr virus
      infection.

PMID- 11827009
TI  - Congenital absence of the inferior rectus muscle in a patient with
      neurofibromatosis.

PMID- 11827010
TI  - Optical coherence tomography and multifocal electroretinography of X-linked
      juvenile retinoschisis.

PMID- 11827011
TI  - Bilateral papilloedema with concomitant neuroretinitis in a 7-year-old girl with
      Lyme disease.

PMID- 11827012
TI  - Post-traumatic endophthalmitis caused by Xanthomonas maltophilia.

PMID- 11827013
TI  - Multiple myeloma presenting with optic nerve compression.

PMID- 11827014
TI  - 'Hyperacute' unilateral anterior uveitis and secondary glaucoma following
      streptokinase infusion.

PMID- 11827015
TI  - Severe ocular injury associated with airbag inflation.

PMID- 11827016
TI  - An interesting case of ligneous conjunctivitis.

PMID- 11827017
TI  - Iris seeding following iridocyclectomy for localised iris melanoma.

PMID- 11827018
TI  - Pulsatile visual phenomenon, ipsilateral to a metastatic orbital carcinoid,
      occurring during usage of sildenafil (Viagra).

PMID- 11827019
TI  - Necrotising fasciitis managed without any surgical intervention.

PMID- 11827020
TI  - Alveolar orbital rhabdomyosarcoma in a patient with neurofibromatosis type 1.

PMID- 11827021
TI  - Ankyloblepharon filiforme adnatum.

PMID- 11827022
TI  - Epstein-Barr virus dacryoadenitis as a complication of bone marrow transplant in
      a child with combined immunodeficiency.

PMID- 11827023
TI  - The opalescence of hydrogel intraocular lens.

PMID- 11827024
TI  - Who should manage primary retinal detachments?

PMID- 11827025
TI  - Who should manage primary retinal detachments?

PMID- 11827026
TI  - Who should manage primary retinal detachments?

PMID- 11827027
TI  - SW-163A and B, novel immunosuppressants produced by Streptomyces sp.
AB  - SW-163A and B, novel immunosuppressants, were isolated from the culture broth of
      Streptomyces sp. SNA15896. The molecular formulas of SW-163A and B were
      determined as C34H42N2O12 and C33H40N2O12 based on the HRFAB-MS analysis,
      respectively. Both compounds were elucidated to be a large ring ester structure
      through spectroscopic analyses including various NMR measurements. SW-163A and B
      showed immunosuppressive and antimicrobial activities in vitro.

PMID- 11827028
TI  - Isolation and structural determination of phepropeptins A, B, C, and D, new
      proteasome inhibitors, produced by Streptomyces sp.
AB  - We have isolated four related compounds named phepropeptins A, B, C, and D, as
      inhibitors of proteasome proposed to regulate many cellular functions. From an
      NMR analysis, the phepropeptins appeared as cyclic hexapeptides, differing in the
      two residues of the constituent amino acids from one another, with four conserved
      amino acid moieties. Based on an amino acid analysis, we synthesized two possible
      cyclic peptides to phepropeptin B that differ in the configurations. A comparison
      of the properties between the natural and synthesized compounds revealed that the
      structure of phepropeptin B was cyclo(-L-Leu-D-Phe-L-Pro-L-Phe-D-Leu-L-Val-). The
      phepropeptins showed inhibition to the proteasomal chymotrypsin-like activity but
      not to alpha-chymotrypsin.

PMID- 11827029
TI  - Chlorogentisylquinone, a new neutral sphingomyelinase inhibitor, produced by a
      marine fungus.
AB  - Chlorogentisylquinone, a new inhibitor of neutral sphingomyelinase activity, was
      purified from the culture broth of a fungal strain FOM-8108 isolated from a
      marine environment by solvent extraction, silica gel chromatography and Sephadex
      LH-20 chromatography. Its chemical structure was elucidated by spectroscopic
      studies including 1H, 13C, DEPT, HMQC and HMBC NMR experiments.
      Chlorogentisylquinone inhibited neutral sphingomyelinase activity of rat brain
      membranes with an IC50 value of 1.2 microM.

PMID- 11827030
TI  - Bisabosquals, novel squalene synthase inhibitors. I. Taxonomy, fermentation,
      isolation and biological activities.
AB  - In the course of screening for yeast squalene synthase inhibitors, bisabosqual A
      was isolated from the culture broth of Stachybotrys sp. RF-7260. The related
      compounds bisabosquals B, C and D were also isolated from Stachybotrys
      ruwenzoriensis RF-6853. Bisabosquals inhibited squalene synthases. IC50 values of
      bisabosqual A against the microsomal squalene synthases from Saccharomyces
      cerevisiae, Candida albicans, HepG2 cell and rat liver were 0.43, 0.25, 0.95 and
      2.5 microg/ml, respectively. Bisabosqual C exhibited inhibitory activities
      similar to bisabosqual A. Bisabosqual A showed broad spectrum antifungal activity
      in vitro.

PMID- 11827031
TI  - Bisabosquals, novel squalene synthase inhibitors. II. Physico-chemical properties
      and structure elucidation.
AB  - The squalene synthase inhibitor bisabosqual A was isolated from the culture broth
      of Stachybotrys sp. RF-7260, and its structure was determined on the basis of
      spectroscopic methods including detailed 2D NMR analyses. The structures of
      bisabosquals B, C and D isolated from Stachybotrys ruwenzoriensis RF-6853 were
      determined by spectroscopic methods and chemical reactions. The absolute
      stereochemistry of bisabosquals A, B and D was determined by X-ray
      crystallographic analysis. They have novel cis-fused tetracyclic structures with
      a bisabolane-type sesquiterpene and phenol moieties.

PMID- 11827032
TI  - CJ-15,183, a new inhibitor of squalene synthase produced by a fungus, Aspergillus
      aculeatus.
AB  - A new squalene synthase (SSase) inhibitor, CJ-15,183 (I) was isolated from the
      fermentation broth of a fungus, Aspergillus aculeatus CL38916. The compound
      potently inhibited rat liver and Candida albicans microsomal SSases and also
      inhibited the human enzyme. It also showed antifungal activities against
      filamentous fungi and a yeast. The structure was determined to be an aliphatic
      tetracarboxylic acid compound consisting of an alkyl gamma-lactone, malic acid
      and isocitric acid moieties by spectroscopic studies.

PMID- 11827033
TI  - A new antibiotic CJ-17,665 from Aspergillus ochraceus.
AB  - A new antibiotic, CJ-17,665 (I) was isolated from the fermentation broth of
      Aspergillus ochraceus, CL41582. It inhibits growth of multi-drug resistant
      Staphylococcus aureus, Streptococcus pyogenes, and Enterococcus faecalis, with
      MICs of 12.5, 12.5 and 25 microg/ml, respectively. The structure contains a
      diketopiperazine and an indole N-oxide moiety that is unusual in natural
      products.

PMID- 11827034
TI  - New pyrrolizidinone antibiotics CJ-16,264 and CJ-16,367.
AB  - Two new antibiotics, CJ-16,264 (I) and CJ-16,367 (II), were isolated from the
      fermentation broth of an unidentified fungus CL39457. These antibiotics have a
      pyrrolizidinone skeleton, first discovered in fungi. Compounds I and II inhibit
      the growth of Gram-positive multi-drug resistant bacteria and some Gram-negative
      strains such as Moraxella catarrhalis and Escherichia coli with altered
      permeability (imp). Comparison of an antibacterial profile between the two
      compounds suggested that the gamma-lactone portion of I is important for the
      activity.

PMID- 11827035
TI  - Pyloricidins, novel anti-helicobacterpylori antibiotics produced by Bacillus sp.
      I. Taxonomy, fermentation and biological activity.
AB  - Novel anti-Helicobacter pylori antibiotics, pyloricidins A, A1, A2, B, C and D,
      were discovered in the culture broth of two bacilli strains. Pyloricidins
      selectively inhibited the growth of H. pylori. Pyloricidin B was efficacious in
      the treatment of gastric infection caused by H. pylori in Mongolian gerbils and
      may be promising for cure of H. pylori infection as a single agent.

PMID- 11827036
TI  - Pyloricidins, novel anti-Helicobacter pylori antibiotics produced by bacillus sp.
      II. Isolation and structure elucidation.
AB  - Novel anti-Helicobacter pylori antibiotics, pyloricidins A, A1, A2, B, C and D
      were isolated from Bacillus sp. HC-70 and Bacillus sp. HC-72 by column
      chromatographies using adsorption and ion exchange resins. Their structures have
      been elucidated based on spectroscopic and degradation studies and shown to be
      peptide-like compounds. These compounds contained two unusual amino acids, viz.,
      5-amino-2,3,4,6-tetrahydroxyhexanoic acid and 3-amino-3-phenylpropionic acid
      (beta-phenylalanine). The structure-activity relationship studies suggested that
      3-(5-amino-2,3,4,6-tetrahydroxyhexanoyl)amino-3-phenylpropionic acid moiety was
      essential for anti-H. pylori activity.

PMID- 11827038
TI  - Effect of solvents on bioconversion of penicillin G to deacetoxycephalosporin G.
AB  - The bioconversion of penicillin G, an inexpensive substrate, to the valuable
      intermediate for semisynthetic cephalosporin production, deacetoxycephalosporin G
      (DAOG), had been recently shown to be increased by eliminating agitation and
      adding decane. The present work examining other solvents shows that all alkanes
      tested are equivalent to decane in activity but that other solvents are either
      inhibitory or less active than alkanes. Optimum conditions of pH and temperature
      for the alkane system are not very different from the previously used aqueous
      system.

PMID- 11827037
TI  - The production of novel sordarin analogues by biotransformation.
AB  - The biotransformation of the fungal protein synthesis inhibitor sordarin is
      reported. Nine taxonomically diverse organisms supported the isolation and
      identification of twelve modified products. The structural diversity of the
      biotransformation products observed and their value in supporting further
      chemistry is discussed.

PMID- 11827039
TI  - Selective production of staplabin and SMTPs in cultures of Stachybotrys
      microspora fed with precursor amines.
AB  - Staplabin and SMTPs, a family of triprenyl phenol metabolites of Stachybotrys
      microspora, enhance fibrinolysis by modulating plasminogen conformation to
      increase its susceptibility to activation by plasminogen activators. We found
      that the production of these metabolites were markedly elevated by feeding the
      microbial culture with an amino acid or an amino alcohol that is a partial
      molecular constituent of the compound. Thus, the addition of 5-aminovaleric acid,
      2-aminoethanol, Ser, Phe, Leu, Trp, Orn and Lys at 100 mg/ml resulted in 7- to 45
      fold increases in the production of staplabin, SMTP-1, -3, -4, -5, -6, -7 and -8,
      respectively. Although the feeding at day 0 to 3 of culture supported the
      selective production, the supplementation after 5 days had little or no effect.
      When non-constituent amino acids were supplemented to cultures, production of
      hitherto uncharacterized congeners was observed.

PMID- 11827040
TI  - Mutagenesis of the rapamycin producer Streptomyces hygroscopicus FC904.
AB  - Rapamycin (RPM) is produced by Streptomyces hygroscopicus FC904 isolated from
      soil in Fuzhou, China. It is a triene macrolide antibiotic with potential
      application as an immunosuppressant and drug for human gene therapy. In an
      attempt to improve rapamycin production, mutation and screening of the parent
      culture have been carried out. Thousands of survivors were obtained after
      mutagenesis by NTG (3 mg/ml) and UV (30 W, 15 cm, 30 seconds) of spore
      suspensions. None showed improved production of RPM. We determined the
      susceptibility to antibiotics of S. hygroscopicus FC904 by two fold dilutions of
      antibiotics in oatmeal agar plates. It was found that the strain was resistant to
      penicillin, erythromycin, RPM, tetracycline and chloramphenicol, but susceptible
      to mitomycin C (MIC, 10 microg/ml) and aminoglycosides such as gentamicin (MIC,
      0.1 microg/ml), kanamycin (MIC, 0.1 microg/ml) and streptomycin (MIC, 0.3
      microg/ml). Protoplasts of strain FC904 were prepared after finding the best
      conditions for their formation. They were treated with gentamicin, erythromycin,
      mitomycin C and NTG. Surprisingly, gentamicin was especially effective for
      obtaining higher RPM-producing mutants. Mutant C14 was selected by exposing the
      protoplasts of the parent strain FC904 to 1 microg/ml of gentamicin at 28 degrees
      C for 2 hours. A higher RPM-producing mutant (C14-1) was obtained from the
      protoplasts of mutant C14 treated with gentamicin, and its titer was 60% higher
      than that of the parent strain FC904 by HPLC analysis. Another improved mutant
      (C14-2) was obtained from the spores of mutant C 14 treated with 1 microg/ml of
      gentamicin plus 2 mg/ml of NTG at 28 degrees C for 2 hours. Mutant C14-2 had a
      titer 124% higher than FC904. The possible mechanism for the effect of gentamicin
      by using protoplasts or spore suspensions will be discussed, i.e. the possibility
      of gentamicin being a mutagen or a selective agent.

PMID- 11827042
TI  - Regulation of tumor necrosis factor-alpha production by a fungal metabolite, PR
      1388.

PMID- 11827041
TI  - L 970843 and L 970844, two new antifungal metabolites from an unidentified fungal
      species HIL Y-903146.

PMID- 11827043
TI  - Roridin L, M and verrucarin M, new macrocyclic trichothecene group antitumor
      antibiotics, from Myrothecium verrucaria.

PMID- 11827044
TI  - Carbon emissions from U.S. ethylene production under climate change policies.
AB  - This paper presents the results from a dynamic computer model of U.S. ethylene
      production, designed to explore implications of alternative climate change
      policies for the industry's energy use and carbon emissions profiles. The model
      applies to the aggregate ethylene industry but distinguishes its main cracker
      types, fuels used as feedstocks and for process energy, as well as the industry's
      capital vintage structure and vintage-specific efficiencies. Results indicate
      that policies which increase the cost of carbon of process energy-such as carbon
      taxes or carbon permit systems-are relatively blunt instruments for cutting
      carbon emissions from ethylene production. In contrast, policies directly
      affecting the relative efficiencies of new to old capital-such as R&D stimuli or
      accelerated depreciation schedules-may be more effective in leveraging the
      industry's potential for carbon emissions reductions.

PMID- 11827045
TI  - Molecular and stable carbon isotopic source identification of oil residues and
      oiled bird feathers sampled along the Atlantic Coast of France after the Erika
      oil spill.
AB  - The Erika tanker broke in two close to the Atlantic coast of France on December
      12, 1999. On December 25th, some heavy fuel oil released by the tanker came
      ashore along the French Atlantic Coast. Some oil residues and oiled bird feathers
      were collected all along the Atlantic Shoreline of France after the wreck of the
      Erika tanker. The aim of this study was to differentiate oil residues and oiled
      bird feathers related to the Erika oil spill from the ones resulting from the
      numerous tar ball incidents which had occurred after the Erika oil spill. Alkane
      and PAH quantification of oil residues allowed differentiation of the samples
      collected on the north part of the Atlantic Coast from those collected on the
      south part of the Atlantic shoreline. All oiled birds appear to have been
      contaminated by the Erika oil. Samples collected on the south part of the
      Atlantic Coast contain a different molecular fingerprint compared to the Erika
      oil indicating that they are not related to the Erika oil spill. Bulk and
      molecular 13C/12C ratio measurements were performed in order to check the
      discriminative feature and the stability of the isotopic approach. Bulk stable
      carbon isotopic composition has been shown to be a valuable screening correlation
      tool as it confirms the link of samples collected in the north part of the
      Atlantic Coast with the Erika oil spill. All the samples collected along the
      south part of the Atlantic Shoreline exhibit 13C-enriched bulk isotopic
      compositions compared to Erika oil. Molecular isotopic composition of saturated
      hydrocarbons and of phenanthrene compounds also allows unambiguous
      differentiation of samples related to the Erika oil spill from those due to tar
      ball incidents. Over the long-term, when molecular distribution will have been
      modified by the different processes affecting oil in the marine environment,
      molecular isotopic composition should then be of particular help for Erika oil
      residues identification.

PMID- 11827046
TI  - The air-sea equilibrium and time trend of hexachlorocyclohexanes in the Atlantic
      Ocean between the Arctic and Antarctica.
AB  - Hexachlorocyclohexanes (HCHs) were determined simultaneously in air and seawater
      during two cruises across the Atlantic Ocean between the Arctic Ocean (Ny
      Alesund/ Svalbard, 79 degrees N; 12 degrees E) and the Antarctic Continent
      (Neumayer Station/ Ekstroem Ice Shelf, 70 degrees S; 8.2 degrees W) in 1999/
      2000. The concentrations of alpha-HCH and gamma-HCH in air and surface waters of
      the Arctic exceeded those in Antarctica by 1-2 orders of magnitude. The gaseous
      concentrations of gamma-HCH were highest above the North Sea and between 20
      degrees N and 30 degrees S. Fugacity fractions were used to estimate the
      direction of the air-sea gas exchange. These showed for alpha-HCH thatthe
      measured concentrations in both phases were close to equilibrium in the North
      Atlantic (78 degrees N-40 degrees N), slightly undersaturated between 30 degrees
      N and 10 degrees S and again close to equilibrium between 20 degrees S and 50
      degrees S. Y-HCH has reached phase equilibrium in the North Atlantic as alpha
      HCH, but the surface waters of the tropical and southern Atlantic were strongly
      undersaturated with y-HCH, especially between 30 degrees N and 20 degrees S.
      These findings are significantly different from two earlier estimates around 1990
      as a result of global emission changes within the past decade. Therefore, we
      investigated the time trend of the HCHs in the surface waters of the Atlantic
      between 50 degrees N and 60 degrees S on the basis of archived samples taken in
      1987-1997 and those from 1999. A decrease of alpha-HCH by a factor of
      approximately 4 is observed at all sampling locations. No decrease of gamma-HCH
      occurred between 30 degrees N and 30 degrees S, but there was a decrease in the
      North Atlantic, North Sea, and in the South Atlantic south of 40 degrees S. The
      constant level of gamma-HCH in the tropical Atlantic confirms the conclusion that
      the tropical Atlantic acts as a sink for y-HCH at present time. The measured
      alpha-HCH seawater concentrations were compared with results from a global
      multimedia fate and transport model. Whereas the time trend over 13 years and the
      latitudinal gradient were well reproduced by the model, the absolute levels were
      too high by a factor of 4.5. This may be explained by the zonal averaging
      employed in the model as well as uncertain emissions and degradation rates.

PMID- 11827047
TI  - Concentrations and spatial variations of polybrominated diphenyl ethers and
      several organochlorine compounds in fishes from the northeastern United States.
AB  - Fish from four lakes, two small lakes in the northeastern United States and two
      of the Great Lakes, were analyzed to determine the concentrations and spatial
      variations of polybrominated diphenyl ethers (PBDE) in this region. Three of the
      lakes were considered to have background levels of PBDEs; one lake was close to a
      suspected source. The PBDE concentrations were compared to organochlorine
      pesticide and PCB concentrations. Age and trophic position did not influence the
      organohalogen concentrations in the fish collected from the four locations. At
      the three background locations, the sum of PBDE concentrations ranged from 6.9 +/
      1.4 to 18 +/- 1 ng/g wet weight, or 150 +/- 9 to 300 +/- 80 ng/g lipid, and
      these values were similar to those of some of the organochlorine pesticides, such
      as total chlordane, but lower than sum of PCB concentrations. At the lake near
      the suspected source, the sum of PBDE concentration was 65 +/- 8 ng/g wet weight,
      or 2,400 +/- 600 ng/g lipid, and it exceeded the sum of PCB concentration. The
      hexabrominated congeners made up 43% of the total mass of PBDEs at this lake, and
      7% at the background locations. Fish to sediment concentration ratios indicated
      that the tetra- through hexa-substituted congeners have a similar
      bioavailability, while the deca-substituted congener does not seem to be
      bioavailable at all.

PMID- 11827049
TI  - Mechanisms of uranium interactions with hydroxyapatite: implications for
      groundwater remediation.
AB  - The speciation of U(VI) sorbed to synthetic hydroxyapatite was investigated using
      a combination of U LIII-edge XAS, synchrotron XRD, batch uptake measurements, and
      SEM-EDS. The mechanisms of U(VI) removal by apatite were determined in order to
      evaluate the feasibility of apatite-based in-situ permeable reactive barriers
      (PRBs). In batch U(VI) uptake experiments with synthetic hydroxyapatite (HA),
      near complete removal of dissolved uranium (>99.5%) to <0.05 microM was observed
      over a range of total U(VI) concentrations up to equimolar of the total P in the
      suspension. XRD and XAS analyses of U(VI)-reacted HA at sorbed concentrations <
      or = 4,700 ppm U(VI) suggested that uranium(VI) phosphate, hydroxide, and
      carbonate solids were not present at these concentrations. Fits to EXAFS spectra
      indicate the presence of Ca neighbors at 3.81 A. U-Ca separation, suggesting that
      U(VI) adsorbs to the HA surfaces as an inner-sphere complex. Uranium(VI)
      phosphate solid phases were not detected in HA with 4700 ppm sorbed U(VI) by
      backscatter SEM or EDS, in agreement with the surface complexation process. In
      contrast, U(VI) speciation in samples that exceeded 7000 ppm sorbed U(VI)
      included a crystalline uranium(VI) phosphate solid phase, identified as
      chernikovite by XRD. At these higher concentrations, a secondary, uranium(VI)
      phosphate solid was detected by SEM-EDS, consistent with chernikovite
      precipitation. Autunite formation occurred at total U:P molar ratios > or = 0.2.
      Our findings provide a basis for evaluating U(VI) sorption mechanisms by
      commercially available natural apatites for use in development of PRBs for
      groundwater U(VI) remediation.

PMID- 11827048
TI  - Historical trends in the lead isotopic composition of archival Sphagnum mosses
      from Scotland (1838-2000).
AB  - The analysis of almost 200 Scottish Sphagnum moss samples collected over the past
      170 years has revealed trends in the isotopic composition of lead similar to
      those previously established for dated Scottish lake sediments and peat bogs,
      lending credibility to these proxy records of atmospheric lead contamination and
      deposition. The effect of temporal variations in contributions from sources such
      as smelting of indigenous lead ores (206Pb/207Pb approximately 1.16-1.18), coal
      combustion (206Pb/207Pb approximately 1.17-1.19), and the use of imported
      Australian lead (206Pb/207Pb approximately 1.04) was clearly seen in the Scottish
      moss 206Pb/207Pb record. This showed some differences from the corresponding
      archival herbage record for the south of England, where the initial influence of
      Australian lead occurred earlier, at the end of the 19th century. A significant
      decline from a 206Pb/ 207Pb value of approximately 1.17 in the Scottish moss
      record began in the 1920s and continued until the 1980s (206Pb/207Pb
      approximately 1.12). The success of measures to reduce lead emissions to the
      atmosphere over the past 20 years in the U.K., in particular from petrol-engined
      vehicles using alkyl lead additives manufactured primarily from Australian lead,
      is evident in both the increasing 206Pb/207Pb ratio and falling lead
      concentration data for Scottish moss.

PMID- 11827051
TI  - The role of mercury redox reactions in snow on snow-to-air mercury transfer.
AB  - Wet deposition of Hg in snow represents a major air-to-land flux of Hg in
      temperate and polar environments. However, the chemical speciation of Hg in snow
      and its chemical and physical behavior after deposition are poorly understood. To
      investigate Hg dynamics in snow, we followed Hg0 and total Hg concentrations in a
      snowpack above a frozen lake over 1 month. Our results indicate that newly
      deposited Hg is highly labile in snowpacks. On average, Hg levels in particular
      snow episodes decrease by 54% within 24 h after deposition. We hypothesize that
      Hg depletion in snow could be caused by a rapid snow-to-air Hg transfer resulting
      from Hg(II) photoinduced reduction to volatile Hg0. Both snowmelt incubated under
      a UV lamp at 17 degrees C and solid snow incubated under the sun at -10 degrees C
      in clear reaction vessels yielded a statistically significant increase in Hg0(aq)
      with time of exposure, while the Hg0(aq) levels remained constant in the dark
      controls. The snow-to-air Hg transfer we observed in this study suggests that the
      massive Hg deposition events observed in springtime in northern environments may
      have less impact than previously anticipated, since once deposited, Hg could be
      rapidly reduced and re-emitted.

PMID- 11827050
TI  - Formation quotients of aluminum sulfate complexes in NaCF3SO3 media at 10, 25,
      and 50 degrees C from potentiometric titrations using a mercury/mercurous sulfate
      electrode concentration cell.
AB  - Mercury/mercurous sulfate electrode concentration cells (with liquid junction)
      are employed in this study to determine the formation constants of aluminum
      sulfate complexes, with the principal advantage that the change in the free
      sulfate concentration is measured directly without the need to know the standard
      potential of the electrode. Potentiometric titrations were conducted at
      temperatures of 10, 25, and 50 degrees C and ionic strengths of approximately
      0.3, 0.5, and 1.0 molal in aqueous solutions of the inert 1:1 electrolyte sodium
      trifluoromethanesulfonate (NaTr). Stoichiometric molal formation quotients Q1 and
      Q2, respectively, for the reactions Al3+(aq) + SO4(2-)(aq) AlSO4+(aq) and
      Al3+(aq) + 2SO4(2-)(aq) <= >Al(SO4)2-(aq) were determined. The values of log Q1
      obtained from this work in NaTr media at ionic strengths of 0.3 and 1.0 mol x kg(
      1) and 50 degrees C (1.72 +/- 0.08 and 1.35 +/- 0.06, respectively) are in
      excellent agreement with the values (1.71 +/- 0.2 and 1.32 +/- 0.1) determined in
      NaCl media from the recent potentiometric study conducted in the same laboratory
      using a hydrogen electrode concentration cell by Ridley et al. (Ridley, M. K.;
      Wesolowski, D. J.; Palmer, D. A.; Kettler, R. M. Geochim. Cosmochim. Acta 1999,
      62, 459-472). The value of log Q2 (2.05 +/- 0.05) in 1.0 mol x kg(-1) from this
      work is smaller than the value reported by Ridley et al. (2.6 +/- 0.5) but within
      the combined experimental error. Empirical isothermal equations are presented to
      permit calculation of the equilibrium quotients as a function of ionic strength
      (0-1 mol x kg(-1)), giving log K1 and log K2 values at 25 degrees C and infinite
      dilution of 3.84 +/- 0.12 and 5.58 + 0.09, respectively. The value for log K1
      obtained in this study at 25 degrees C is bracketed within experimental
      uncertainty by values reported by Kryzhanovskii et al. (Kryzhanovskii, M. M.;
      Volokhov, Y. A.; Pavlov, L. N.; Eremin, N. I.; Mironov, V. E Zh. Prikl. Khim.
      1971, 44,476-479) and Nishide and Tsuchiya (Nishide, T.; Tsuchiya, R. Bull. Chem.
      Soc. Jpn. 1965, 38, 1398-1400), namely, 3.89 and 3.73, respectively. All other
      literature values for the first aluminum sulfate association constant are
      considerably lower than these results, which is also true for the second
      association constant, although there are few experimental data available for the
      latter. Empirical equations are also presented for calculating values of log Q1
      and log Q2 from 0 to 1 molal ionic strength and from 10 to 125 degrees C,
      spanning the range of most environmental conditions at which these reactions are
      important.

PMID- 11827052
TI  - Effect of molecular scale roughness of glass beads on colloidal and bacterial
      deposition.
AB  - Molecular-scale surface roughness and charge heterogeneity have been hypothesized
      as factors that can affect the deposition rates of colloids during their
      transport in porous media. To test their relative importance, a single batch of
      cleaned glass beads was divided in half and chemically treated with acid or base
      to alter surface roughness. Analysis of the topography of 20 glass beads with an
      atomic force microscope (AFM) indicated that the chromic acid-treated (rough)
      beads had a root-mean-square roughness of 38.1 +/- 3.9 nm, while the sodium
      hydroxide-treated (smooth) beads had root-mean-square surface roughness of 15.0
      +/- 1.9 nm. AFM force volume imaging of glass bead surfaces did not reveal
      surface charge heterogeneity. Filtration experiments with inorganic colloids
      (latex microspheres, 1 microm diameter) consistently demonstrated that there was
      a greater retention of latex microspheres on rough than smooth glass beads
      suspended in either low (10(-5) M) or higher (10(-1) M) ionic strength (IS)
      solutions. Collision efficiencies for rough beads were 30-50% larger than for
      smooth beads. Collision efficiencies of bacteria using rough glass beads were
      also equal to or greater than those measured for smooth beads. In experiments
      with the perchlorate-reducing bacterial isolate KJ, collision efficiencies were
      significantly greater on rough rather than smooth beads for two different ionic
      strength solutions (IS = 0.05 or 1 M). In another case (IS = 0.1 M) for KJ, and
      in filtration experiments with E coli, collision efficiencies were not
      significantly different between the rough and smooth beads. We hypothesize that
      the consistently greater deposition rates of microspheres, but not bacteria, on
      rough rather than smooth beads are due in part to the presence of polymers on the
      surfaces of bacteria.

PMID- 11827053
TI  - In situ MTBE biodegradation supported by diffusive oxygen release.
AB  - Microcosm studies with sediments from Vandenberg Air Force Base, CA, suggest that
      native aerobic methyl tert-butyl ether (MTBE)-degrading microorganisms can be
      stimulated to degrade MTBE. In a series of field experiments, dissolved oxygen
      has been released into the anaerobic MTBE plume by diffusion through the walls of
      oxygen-pressurized polymeric tubing placed in contact with the flowing
      groundwater. MTBE concentrations were decreased from several hundred to less than
      10 microg/L during passage through the induced aerobic zone, due apparently to in
      situ biodegradation: abiotic MTBE loss mechanisms were insignificant. Lag time
      for initiation of degradation was less than 2 months, and the apparent pseudo
      first-order degradation rate was 5.3 day(-1). Additional MTBE was added in steps
      to raise the influent concentration to a maximum of 2.1 mg/L. With each step,
      MTBE was degraded within the preestablished aerobic treatment zone at rates
      ranging from 4.4 to 8.6 day(-1). Excess dissolved oxygen suggested that even
      higher MTBE concentrations could have been treated. Continued flow through the
      treatment zone was repeatedly confirmed through tracer and other tests. These and
      others' results suggest that it is possible to create permeable in situ treatment
      zones solely by releasing oxygen to support native microbial degradation of MTBE.

PMID- 11827054
TI  - Influence of biodegradation processes on the duration of CaCO3 as a pH buffer in
      municipal solid waste incinerator bottom ash.
AB  - The long-term leachability of heavy metals from municipal solid waste incinerator
      (MSWI) bottom ash is of concern because of its potential use as a secondary
      construction material. Calcite is the most important long-term buffer in MSWI
      bottom ash as it buffers solutions during percolation and is an important factor
      in the control of heavy-metal mobility. It has been argued that biodegradation of
      residual organic material in the MSWI is a significant source of acidity. Model
      calculations have therefore been carried out to determine the influence of
      biodegradation on the longevity of the calcite buffer. Using the program
      STEADYQL, which couples thermodynamic equilibrium with kinetically controlled
      reactions, solution composition was estimated at steady state. The concentration
      of Ca dissolved from calcite was estimated in the presence and absence of gypsum
      as a function of the reaction rate of a number of slow reactions: aerobic,
      ferrogenic, sulfogenic, and methanogenic biodegradation; diffusion of O2 into the
      system; degassing of CO2 out of the system; and dissolution of Ca silicate. It
      was found that, independent of the rate, the biodegradation of organic matter had
      little influence on the longevity of the calcite buffer (between 2,000 and 3,000
      yr for a deposit of 1 m in depth), that anaerobic biodegradation may have a
      slight retarding effect, and that calcite dissolution due to acid input via
      precipitation was negligible (around 3% of the total at reference conditions for
      rainwater with a pH value of 4.3).

PMID- 11827055
TI  - Environmental behavior of the chiral acetamide pesticide metalaxyl:
      enantioselective degradation and chiral stability in soil.
AB  - Racemic metalaxyl is currently being replaced in many countries by metalaxyl-M,
      the fungicide enantiomerically enriched with the biologically active R
      enantiomer. This "chiral switch" is expected to reduce the amount of pesticide
      released into the environment as well as potential side-effects on nontarget
      organisms. Detailed knowledge of the environmental behavior of such chiral
      compounds should include information on the chiral stability (interconversion of
      enantiomers). In the present study, the degradation/ dissipation of metalaxyl and
      its primary carboxylic acid metabolite (MX-acid) in soil was investigated under
      laboratory conditions using enantioselective gas chromatography mass spectrometry
      (GC-MS). Racemic and the enantiopure R- and S-compounds were incubated in
      separate experiments. The degradation of metalaxyl was shown to be
      enantioselective with the fungicidally active R-enantiomer being faster degraded
      than the inactive S-enantiomer, resulting in residues enriched with S-metalaxyl
      when the racemic compound was incubated. The relatively high enantioselectivity
      suggests that degradation/dissipation was largely biological. The data indicated
      a conversion of 40-50% of metalaxyl to MX-acid, and the remaining metalaxyl being
      degraded via other pathways. The degradation of MX-acid was also
      enantioselective. Metalaxyl and MX-acid were both configurationally stable in
      soil, showing no interconversion of R- to S-enantiomers, and vice-versa.
      Furthermore, the conversion of metalaxyl to MX-acid proceeded with retention of
      configuration. Degradation followed approximate first-order kinetics but showed
      significant lag phases.

PMID- 11827056
TI  - Influence of wettability on the recovery of NAPLs from alluvium.
AB  - The physicochemical characteristics of five nonaqueous phase liquids (NAPLs)
      recovered from contaminated alluvial aquifers are presented. The five include two
      chlorinated degreasing solvents, one chlorinated dry-cleaning solvent and two
      weathered fuel hydrocarbons. In addition to density, viscosity, and interfacial
      tensions, the equivalent alkane carbon number (EACN), spreading coefficients and
      Amott-Harvey and USBM wettability indices with respect to alluvial aquifer
      materials are used as a means to characterize three of these NAPLs.
      Experimentally measured spreading coefficients of four of these NAPLs illustrate
      that field NAPLs can have positive initial spreading coefficients. Furthermore,
      capillary desaturation curves for two NAPLs with alluvial aquifer material
      collected from the NAPL zone are presented as an additional and important means
      to infer the practical implications of the wetting characteristics on the
      efficacy of NAPL recovery. The results from the wettability and capillary
      desaturation experiments show that these NAPLs are mixed-wet to oil-wet when
      measured in the alluvium from their respective field sites. Furthermore, these
      results indicate that the displacement of NAPLs from soils by water is more
      difficult for mixed-wet or oil-wet soils than it is for water-wet or weakly water
      wet soils. Finally experimental data indicate that adding anionic surfactants to
      the water shifts the wettability toward water-wet and makes the NAPL easier to
      displace and recover.

PMID- 11827057
TI  - Sonochemical desorption and destruction of 4-chlorobiphenyl from synthetic
      sediments.
AB  - The application of ultrasound for the treatment of polychlorinated biphenyl (PCB)
      contaminated sediments was explored in this study with a model system of 4
      chlorobiphenyl (4-CB) and synthetic sediments. In the presence of an ultrasonic
      probe, operating at 20 kHz with a power density of 460 W L(-1), more than 90% of
      4-CB in aqueous homogeneous solution was destroyed after 20 min, with an apparent
      first-order rate constant, k, of 0.120 min(-1). In addition, experiments
      investigating the destruction of dissolved 4-CB in the presence of bare silica or
      alumina particles or dissolved humic acid (HA) had lower degradation rates than
      in aqueous homogeneous solutions. Increasing the bare particle concentration or
      dissolved HA concentration further lowered the degradation rate. However, in
      investigating the desorption and destruction of sorbed 4-CB from humic acid laden
      alumina particles, the effect of particles and released dissolved HA on the
      degradation rate are simply additive, and desorption of 4-CB does not appear to
      further complicate the system. A kinetic analysis of the system revealed that
      desorption of 4-CB from particles was not a limiting factor in this system.

PMID- 11827058
TI  - Risk based management of contaminated sediments: consideration of spatial and
      temporal patterns in exposure modeling.
AB  - This paper addresses interactions among foraging behavior, habitat preferences,
      site characteristics, and spatial distribution of contaminants in developing PCB
      exposure estimates for winter flounder at a hypothetical open water dredged
      material disposal site in the coastal waters of New York and New Jersey (NY-NJ).
      The implications of these interactions for human health risk estimates for local
      recreational anglers who fish for and eat flounder are described. The models
      implemented in this study include a spatial submodel to account for spatial and
      temporal characteristics of fish exposures and a probabilistic adaptation of the
      Gobas bioaccumulation model that accounts for temporal variation in
      concentrations of hydrophobic contaminants in sediment and water. We estimated
      the geographic distribution of a winter flounder subpopulation offshore of NY-NJ
      based on species biology and its vulnerability to local recreational fishing, the
      foraging area of individual fish, and their migration patterns. We incorporated
      these parameters and an estimate of differential attraction to a management site
      into a spatially explicit model to assess the range of exposures within the
      population. The output of this modeling effort, flounder PCB tissue
      concentrations, provided exposure point concentrations for an estimate of human
      health risk through ingestion of locally caught flounder. The risks obtained for
      the spatially nonexplicit case are as much as 1 order of magnitude higher than
      those obtained with explicit consideration of spatial and temporal
      characteristics of winter flounder foraging and seasonal migration. This practice
      of "defaulting" to extremely conservative estimates for exposure parameters in
      the face of uncertainty ill serves the decision-making process for management of
      contaminated sediments in general and specifically for disposal of dredged
      materials. Consideration of realistic spatial and temporal scales in food chain
      models can help support sediment management decisions by providing a quantitative
      expression of the confidence in risk estimates.

PMID- 11827059
TI  - Biofiltration of methyl tert-butyl ether vapors by cometabolism with pentane:
      modeling and experimental approach.
AB  - Degradation of methyl tert-butyl ether (MTBE) vapors by cometabolism with pentane
      using a culture of pentane-oxidizing bacteria (Pseudomonas aeruginosa) was
      studied in a 2.4-L biofilter packed with vermiculite, an inert mineral support.
      Experimental pentane elimination capacity (EC) of approximately 12 g m(-3) h(-1)
      was obtained for an empty bed residence time (EBRT) of 1.1 h and inlet
      concentration of 18.6 g m(-3). For these experimental conditions, EC of MTBE
      between 0.3 and 1.8 g m(-3) h(-1) were measured with inlet MTBE concentration
      ranging from 1.1 to 12.3 g m(-3). The process was modeled with general mass
      balance equations that consider a kinetic model describing cross-competitive
      inhibition between MTBE (cosubstrate) and pentane (substrate). The experimental
      data of pentane and MTBE removal efficiencies were compared to the theoretical
      predictions of the model. The predicted pentane and MTBE concentration profiles
      agreed with the experimental data for steady-state operation. Inhibition by MTBE
      of the pentane EC was demonstrated. Increasing the inlet pentane concentration
      improved the EC of MTBE but did not significantly change the EC of pentane. MTBE
      degradation rates obtained in this study were much lower than those using
      consortia or pure strains that can mineralize MTBE. Nevertheless, the system can
      be improved by increasing the active biomass.

PMID- 11827060
TI  - Dissolved gases as partitioning tracers for determination of hydrogeological
      parameters.
AB  - In this study, dissolved Kr and SF6 gases were used to determine various
      hydrogeological parameters of laboratory columns under water-saturated and
      partially saturated conditions as a function of the flow velocity. The dissolved
      gases behaved conservatively in saturated columns but were significantly retarded
      in unsaturated conditions as a direct function of the Henry's law constant (KH)
      and the ratio of column pore spaces filled with air and water (Vg/Vw). Lower
      aqueous diffusion coefficients for SF6 compared to that for Kr also resulted in
      significant rate-limited mass transport across gas-water interface. This effect
      was exacerbated at higher flow velocities as was indicated by the asymmetric
      shape of breakthrough curves, more so in the case of SF6. A nonequilibrium
      advective-dispersive transport model accurately described tracer breakthrough and
      was used to estimate parameters such as final Vg/Vw under partially saturated
      conditions and partitioning rates. Internally consistent model results were
      obtained for both dissolved gases despite the wide range in physical properties
      (e.g., KH and aqueous diffusion coefficients), suggesting that dissolved Kr and
      SF6 may be used in conjunction to delineate and validate aquifer characteristics
      simultaneously from a single pulse injection of the tracer.

PMID- 11827061
TI  - De novo synthesis of PCDD/F by thermogravimetry.
AB  - On the basis of laboratory experiments with model mixtures, the steps in the de
      novo synthesis of halogenated compounds were studied. The study was performed
      using a thermobalance to evaluate the temperature of the maximum rate and the
      kinetics of the decomposition of the materials in the presence of air. The effect
      of the presence of CuCl2 and CuO with an atmosphere of HCl was studied. Analysis
      of the volatiles and solids after combustion in a horizontal furnace confirms the
      presence of organochloride compounds (including PCDD/F) at various temperatures.
      With the procedure that we followed, combustion is separated from pyrolysis, and
      it is possible to analyze the essential factors involved in the combustion
      process.

PMID- 11827062
TI  - Prediction of in-use emissions of heavy-duty diesel vehicles from engine testing.
AB  - A model of a heavy-duty vehicle driveline with automatic transmission has been
      developed for estimating engine speed and load from vehicle speed. The model has
      been validated using emissions tests conducted on three diesel vehicles on a
      chassis dynamometer and then on the engines removed from the vehicles tested on
      an engine dynamometer. Nitrogen oxide (NOx) emissions were proportional to work
      done by the engine. For two of the engines, the NOx/horsepower(HP) ratio was the
      same on the engine and on the chassis dynamometer tests. For the third engine
      NOx/HP was significantly higher from the chassis test, possibly due to the use of
      dual engine maps. The engine certification test generated consistently less
      particulate matter emissions on a gram per brake horsepower-hour basis than the
      Heavy Duty Transient and Central Business District chassis cycles. A good linear
      correlation (r2 = 0.97 and 0.91) was found between rates of HP increase
      integrated over the test cycle and PM emissions for both the chassis and the
      engine tests for two of the vehicles. The model also shows how small changes in
      vehicle speeds can lead to a doubling of load on the engine. Additionally, the
      model showed that it is impossible to drive a vehicle cycle equivalent to the
      heavy-duty engine federal test procedure on these vehicles.

PMID- 11827063
TI  - The effects of the catalytic converter and fuel sulfur level on motor vehicle
      particulate matter emissions: gasoline vehicles.
AB  - Scanning mobility and electrical low-pressure impactor particle size measurements
      conducted during chassis dynamometer testing reveal that neither the catalytic
      converter nor the fuel sulfur content has a significant effect on gasoline
      vehicle tailpipe particulate matter (PM) emissions. For current technology, port
      fuel injection, gasoline engines, particle number emissions are < or = 2 times
      higher from vehicles equipped with blank monoliths as compared to active
      catalysts, insignificant in contrast to the 90+% removal of hydrocarbons. PM mass
      emission rates derived from the size distributions are equal within the
      experimental uncertainty of 50-100%. Gravimetric measurements exhibit a 3-10-fold
      PM mass increase when the active catalyst is omitted, which is attributed to
      gaseous hydrocarbons adsorbing onto the filter medium. Both particle number and
      gravimetric measurements show that gasoline vehicle tailpipe PM emissions are
      independent (within 2 mg/mi) of fuel sulfur content over the 30-990 ppm
      concentration range. Nuclei mode sulfate aerosol is not observed in either test
      cell measurements or during wind tunnel testing. For three-way catalyst equipped
      vehicles, the principal sulfur emission is SO2; however a sulfur balance is not
      obtained over the drive cycle. Instead, sulfur is stored on the catalyst during
      moderate driving and then partially removed during high speed/load operation.

PMID- 11827064
TI  - The effects of the catalytic converter and fuel sulfur level on motor vehicle
      particulate matter emissions: light duty diesel vehicles.
AB  - Wind tunnel measurements and direct tailpipe particulate matter (PM) sampling are
      utilized to examine how the combination of oxidation catalyst and fuel sulfur
      content affects the nature and quantity of PM emissions from the exhaust of a
      light duty diesel truck. When low sulfur fuel (4 ppm) is used, or when high
      sulfur (350 ppm)fuel is employed without an active catalyst present, a single log
      normal distribution of exhaust particles is observed with a number mean diameter
      in the range of 70-83 nm. In the absence of the oxidation catalyst, the high
      sulfur level has at most a modest effect on particle emissions (<50%) and a minor
      effect on particle size (<5%). In combination with the active oxidation catalyst
      tested, high sulfur fuel can lead to a second, nanoparticle, mode, which appears
      at approximately 20 nm during high speed operation (70 mph), but is not present
      at low speed (40 mph). A thermodenuder significantly reduces the nanoparticle
      mode when set to temperatures above approximately 200 degrees C, suggesting that
      these particles are semivolatile in nature. Because they are observed only when
      the catalyst is present and the sulfur level is high, this mode likely originates
      from the nucleation of sulfates formed over the catalyst, although the
      composition may also include hydrocarbons.

PMID- 11827065
TI  - Calibrating the uptake kinetics of semipermeable membrane devices in water:
      impact of hydrodynamics.
AB  - The use of lipid-containing semipermeable membrane devices (SPMDs) is becoming
      commonplace, but the potential effects of environmental variables affecting the
      accumulation of contaminants into SPMDs had not been characterized sufficiently,
      yet. To characterize the effect of hydrodynamic conditions on the contaminant
      uptake kinetics, accumulation of pentachlorobenzene, hexachlorobenzene, and
      hexachlorocyclohexane isomers from water into SPMD was studied at various water
      flow rates. The accumulation kinetics of hydrophobic compounds (log Kow > 4) are
      governed by the aqueous boundary layer in linear flow velocity range from 0.06 to
      0.28 cm s(-1) and sensitive to slight changes in flow rate. The effect of flow
      velocity on the exchange kinetics increases with increasing hydrophobicity. Under
      faster, but still laminar flow conditions (0.28-1.14 cm s(-1)), the sensitivity
      to changes in flow decreases to a nonsignificant level for the substances under
      consideration. The results of this study confirm that the use of the laboratory
      derived calibration data for estimation of analyte concentrations in the ambient
      environment is limited unless flow-sensitive performance reference compounds are
      used.

PMID- 11827066
TI  - Cell biology and clinical implications of adhesion molecules in colorectal
      diseases: colorectal cancers, infections and inflammatory bowel diseases.
AB  - Adhesion molecules are transmembrane proteins that can anchor cytoskeletal
      proteins on the cytoplasmic side of the cell membrane, while also connecting
      extracellular structures on the outer surface of the cell membrane. In addition
      to physical linkages between the extracellular environment and the cytoskeleton,
      adhesive complexes participate in important signal transduction systems as
      modulators or receptors. Their functions in cell signaling are probably at least
      as important as their cytoskeletal and cell attachment properties. Understanding
      these regulatory functions appears to be of importance in determining of
      pathological characteristic of numerous diseases. Expression and functional
      activity of various adhesion molecules have been found in different diseases
      affecting the colorectum. In this review we summarize recent advantages about the
      cell biology these diseases and clinical implications.

PMID- 11827067
TI  - Experimental and clinicopathologic studies on the function of the HGF receptor in
      human colon cancer metastasis.
AB  - The organ-specific metastasis characterizes several human cancers, including
      colon carcinoma, a disease that frequently involves metastases in the liver. The
      data on the molecular mechanisms of liver metastasis would therefore be highly
      useful for prognostic purposes. Although the upregulation/amplification of the
      hepatocyte growth factor (HGF) receptor, c-met, has been frequently observed in
      colon cancer metastasis, the actual functional significance of the feature in the
      liver metastatization is not yet known. We have used three human colon carcinoma
      cell lines (HT29, HT25 and WiDr), characterized by different liver metastatic
      potentials in SCID mice, to analyze the expression of c-met and the biological
      effects of HGF. We found that HGF induces scattering in in vitro liver-metastatic
      cell lines (HT25 and WiDr) only at doses which are non-mitogenic (1-20 ng/ml).
      Analysis of the c-met expression revealed that the metastatic cell lines express
      authentic c-met gene and protein material, unlike the non-metastatic HT29 cell
      line, which expresses only the c-terminal cytoplasmic domain of the c-met beta
      chain. Interestingly, c-met was found to be localized in the substrate-attached
      peripheral membrane and partially colocalized with phosphotyrosine-proteins in
      the metastatic cells only when kept on fibronectin. On the other hand, we have
      analyzed 86 primary human colon cancers in Dukes' B (invasive but non-metastatic)
      and C (invasive and lymph node metastatic) stages. Western blotting of the
      proteins isolated from the tumor tissues and immunohistochemical control study on
      the paraffin samples of a third of these cases (25/86) all indicated a
      significant upregulation of the c-met protein in the Dukes' C tumor glands
      compared to the Dukes' B stages (P < 0.001 and P < 0.05, respectively). Since the
      two stages differ in the involvement of the regional lymph nodes but not in the
      invasion depth, the clinicopathological data and our experimental findings
      further support the notion that the c-met expression in human colon cancer can be
      considered as a marker of the metastatic potential due to its involvement in the
      generation of the motility signal.

PMID- 11827068
TI  - Differences of vascular endothelial growth factor (VEGF) expression between liver
      and abdominal metastases from colon cancer. Implications for the treatment with
      VEGF inhibitors.
AB  - The vascular endothelial growth factor (VEGF) plays a central role in promoting
      angiogenesis, and it is the target of innovative anti-cancer therapies. In
      colorectal carcinomas, differences in the VEGF expression have been found between
      the primary tumor and its metastases. We postulated that differences in the VEGF
      expression may also exist between liver and abdominal metastases from colon
      cancer. Consecutive colon cancer patients with liver or abdominal metastases were
      considered eligible for the study. Biopsies had to be performed before
      chemotherapy and the VEGF analysis were conducted through immunohistochemistry.
      The staining results were correlated to the metastatic pattern. The study
      population consisted of 41 patients with a metastatic site in the liver in 19
      patients and the abdomen in 22 patients. A positive VEGF staining was found in 19
      of the 41 metastatic samples (46%). Cases with positive VEGF expression were
      found more frequently in abdominal (15 out of 22 patients; 68%) than in liver
      metastases (4 out of 19 patients; 21%). Also, the degree of VEGF immunoreactivity
      was significantly higher in abdominal than in liver metastases. Evidence is
      supported that the VEGF expression may be different between colon cancer
      metastatic sites. The efficacy of anti-VEGF treatments may depend on the VEGF
      expression status, and this finding deserves further investigation.

PMID- 11827069
TI  - Suppression by apigenin of peritoneal metastasis of intestinal adenocarcinomas
      induced by azoxymethane in Wistar rats.
AB  - The effect of a naturally occurring flavonoid apigenin on the development of
      bombesin-enhanced peritoneal metastasis from intestinal adenocarcinomas induced
      by azoxymethane was investigated in male Wistar rats. From the start of the
      experiment, rats were given weekly s.c. injections of azoxymethane (7.4 mg/kg
      body weight) for 10 weeks and s.c. injection of bombesin (40 microg/kg body
      weight) every other day, and from week 16, s.c. injections of apigenin (0.75 or
      1.5 mg/kg body weight) every other day until the end of the experiment in week
      45. Bombesin significantly increased the incidence of intestinal tumors and
      cancer metastasis to the peritoneum in week 45. It also significantly increased
      the labeling index of intestinal cancers. Although administration of apigenin at
      either dose with bombesin had little or no effect on the enhancement of
      intestinal carcinogenesis by bombesin, the location, histologic type, depth of
      involvement, infiltrating growth patterns and labeling index, it was found to
      decrease significantly the incidence of cancer metastasis. Apigenin significantly
      decreased the incidence of lymphatic vessel invasion of adenocarcinomas, which
      was enhanced by bombesin. In vitro experiments revealed that apigenin inhibited
      bombesin-enhanced phosphorylation of mitogen-activated protein kinase (MAPK), but
      not matrix metalloprotease (MMP)-9 expression. Our findings indicate that
      apigenin inhibits cancer metastasis through inhibition of phosphorylation of
      MAPK.

PMID- 11827071
TI  - Identification of cis-acting promoter elements that support expression of
      membrane-type 1 matrix metalloproteinase (MT1-MMP) in v-src transformed Madin
      Darby canine kidney cells.
AB  - Membrane-type 1 matrix metalloproteinase (MT1-MMP) expressed in tumor cells is
      believed to be important for the pericellular degradation of extracellular
      matrices during invasion and metastasis. To analyze the mechanism by which MT1
      MMP becomes expressed in cancer cells, we assessed the MT1-MMP promoter region
      for the presence of cis-acting promoter elements that support transcription in
      transformed cells. Our tumor model consisted of Madin-Darby canine kidney (MDCK)
      cells transformed by v-src (src4 cells). MT1-MMP mRNA was only faintly detected
      in parental cells but was strongly expressed in the src4 cells. In parallel, src4
      cells invaded into collagen gels, whereas MDCK cells did not. When MDCK and src4
      cells were transiently transfected with a plasmid containing of -3000 to -99 nt
      from the upstream region of the MT1-MMP gene, the promoter activity was 2.6-fold
      higher in src4 cells than in MDCK cells. Furthermore, the region between -399 and
      -356 nt was found to contain the src4-specific enhancer element(s). Tandem Sp1
      binding sites were also found to be essential in promoting transcription. An Egr
      1 site that partially overlaps with the Sp1 sites was found to cooperate with the
      src4-specific enhancer and to also contribute weakly to the basal promoter
      activity. The presence of transcription factors that bind to the src4-specific
      enhancer site was detected by mobility-shift assays in src4 cell nuclear extracts
      but only weakly in MDCK extracts. Thus, we have identified a novel enhancer
      element that acts specifically in the transformed cells to enhance MT1-MMP
      expression.

PMID- 11827070
TI  - In vitro effects of cholesteryl butyrate solid lipid nanospheres as a butyric
      acid pro-drug on melanoma cells: evaluation of antiproliferative activity and
      apoptosis induction.
AB  - Literature data show that butyric acid derivatives bear a dose-dependent
      differentiative anti-proliferative activity on cancer cell lines and that
      apoptosis induction may play a major role. Although it was recently shown that
      solid lipid nanospheres (SLNs) are a suitable tool for several in vivo drug
      administration routes, there is little available information on melanoma cell
      lines. This study was aimed at evaluating the anti-proliferative and apoptotic in
      vitro effects of cholesteryl butyrate (chol-but) SLNs on melanoma cells.
      Increasing concentrations of chol-but SLNs were used to test two melanoma cell
      lines. Both cell lines were treated with Na-butyrate (Na-but) and chol-but SLNs
      for viability. Those tested with chol-but SLNs were more effective than Na
      butirate (3 to 72 h). The apoptotic effects of chol-but SLNs were evaluated
      between 3 and 72 h by annexin-V (ANX-V)/propidium iodide (PI) staining and the
      antiproliferative effect by PI staining. Apoptosis anti-proliferative-regulatory
      proteins as bcl-2, Fas/APO1 (CD95) and PCNA (PC10) were also investigated. Flow
      cytometric analyses evidenced a G(0/1)-S transition block and a 'sub-G(0/1)'
      apoptotic peak from 0.5 to 1.0 mM butyric acid. In ANX-V/PI flow cytometric
      staining, a dose- and time-dependent increase in the apoptotic cell percentage
      (ANX-V+) coupled with a down-regulation of PC10 and bcl-2 and a parallel up
      regulation of Fas/APO1 (CD95) were found in both lines started after 3 to 24 h of
      chol-but SLNs treatment. Results show that chol-but SLNs exerts a dose/time
      dependent effect in melanoma cell apoptosis induction between 3 and 24 h and a
      dose but not time-dependent effect after 24 h of treatment.

PMID- 11827072
TI  - Analysis of mechanisms underlying BRMS1 suppression of metastasis.
AB  - Introduction of normal, neomycin-tagged human chromosome 11 (neo11) reduces the
      metastatic capacity of MDA-MB-435 human breast carcinoma cells by 70-90% without
      affecting tumorigenicity. Differential display comparing MDA-MB-435 and neo11/435
      led to the discovery of a human breast carcinoma metastasis suppressor gene,
      BRMS1, which maps to chromosome 11q13.1-q13.2. Stable transfectants of MDA-MB-435
      and MDA-MB-231 breast carcinoma cells with BRMS1 cDNA still form progressively
      growing, locally invasive tumors when injected in mammary fat pads of athymic
      mice but exhibit significantly lower metastatic potential (50-90% inhibition) to
      lungs and regional lymph nodes. To begin elucidating the mechanism(s) of action,
      we measured the ability of BRMS1 to perturb individual steps of the metastatic
      cascade modeled in vitro. Consistent differences were not observed for adhesion
      to extracellular matrix components (laminin, fibronectin, type IV collagen, type
      I collagen, Matrigel); growth rates in vitro or in vivo; expression of matrix
      metalloproteinases, heparanase, or invasion. Likewise. BRMS1 expression did not
      up regulate expression of other metastasis suppressors, such as NM23, Kai1, KiSS1
      or E-cadherin. Motility of BRMS1 transfectants was modestly inhibited (30-60%)
      compared to parental and vector-only transfectants. Ability to grow in soft agar
      was also decreased in MDA-MB-435 cells by 80-89%, but the decrease for MDA-MB-231
      was less (13-15% reduction). Also, transfection and re-expression of BRMS1
      restored the ability of human breast carcinoma cells to form functional homotypic
      gap junctions. Collectively, these data suggest that BRMS1 suppresses metastasis
      of human breast carcinoma by complex, atypical mechanisms.

PMID- 11827074
TI  - Memory for multidimensional source information.
AB  - Source memory may comprise recollection of multiple features of the encoding
      episode. To analyze the simultaneous representation and retrieval of those
      multiple features, a multinomial memory model is presented that measures memory
      for crossed dimensions of source information. The first experiment investigated
      the validity of the new model. The model showed an excellent statistical fit to
      empirical data, and the parameters of multidimensional source memory were
      sensitive to manipulations of source similarity on distinct dimensions. The
      second experiment used the model to test the hypothesis that source memory for
      individual context attributes is stochastically related in the case of conscious
      recollection but independent in the case of familiarity-based recognition
      judgments. The prediction was supported by the introduction of a "remember"
      "know" distinction in a multidimensional source memory test.

PMID- 11827073
TI  - Comparison of vascularity and angiogenesis in primary invasive mammary carcinomas
      and in their respective axillary lymph node metastases.
AB  - It is well established that the ability of a neoplasm to induce a blood supply
      from a pre-existing circulation (angiogenesis) is a major factor in tumour
      growth, invasion and metastasis. However, the angiogenic potential of metastases
      and their subsequent growth have not been extensively studied. The question
      arises: can metastatic clones induce the same level of angiogenesis as in the
      primary neoplasm they emanated from? In this study it is hypothesised that in the
      same patient the level of vascularity and angiogenesis is the same in both the
      primary invasive ductal carcinoma and in the axillary lymph node metastasis at
      the time of surgery, according to Kerbels theory of clonal-dominance. To directly
      address the hypothesis, morphological measures of the established blood/lymphatic
      circulation (vascularity) as well as estimates of angiogenesis (endothelial cell
      proliferation) were measured in primary tumours and directly compared to the same
      parameters in the corresponding lymph node metastasis in a case by case basis (n
      = 17). The results demonstrate varying associations between the level of
      vascularity and angiogenesis between matched individual tumours and their
      metastatic lymph nodal deposits. It is possible that either variations in the
      angiogenic characteristics of the metastasising clone or local or systemic
      promoters or inhibitors of angiogenesis influence tumour angiogenesis at the
      different sites.

PMID- 11827075
TI  - Capturing the suffix: cognitive streaming in immediate serial recall.
AB  - Adding an irrelevant item to the end of an auditory to-be-remembered list
      increases error on the last list items appreciably, known as the suffix effect.
      The phenomenon of auditory capture (e.g., Bregman & Rudnicky, 1975), namely, the
      tendency for a sequence of similar items to form a stream that at the same time
      isolates perceptually dissimilar members of the sequence, is exploited to explore
      the suffix effect. Irrelevant items interleaved between to-be-remembered items
      are used to capture the suffix with the aim of reducing its impact. Four
      experiments illustrate how the properties of the irrelevant sequence promote
      capture. The results are problematic for models of the suffix that involve
      masking of the last list item; instead, models based on grouping are favored.

PMID- 11827077
TI  - Environmental context and recognition: the role of recollection and familiarity.
AB  - Evidence for effects of changed environmental context on recognition has been
      equivocal. Using 3 experiments, the author investigated the role of environmental
      context from a dual-processing approach. Experiment 1 showed that testing word
      recognition in a novel context led to a reliable decrement but only for
      recognition accompanied by conscious recollection, with familiarity-based
      recognition judgments being unaffected. This was replicated in Experiment 2 using
      stimuli that were novel to the participants (nonwords). Experiment 3 showed that
      the decrement in recollection also occurred when the changed-context condition
      involved presenting items in a different but familiar context. The results
      suggest that effects of environmental context will only be found when recognition
      is accompanied by conscious recollection and that this effect is due to a
      specific item-context association.

PMID- 11827078
TI  - Intrinsic frames of reference in spatial memory.
AB  - Three experiments investigated the frames of reference used in memory to
      represent the spatial structure of the environment. Participants learned the
      locations of objects in a room according to an intrinsic axis of the
      configuration; the axis was different from or the same as their viewing
      perspective. Judgments of relative direction using memory were most accurate for
      imagined headings parallel to the intrinsic axis, even when it differed from the
      viewing perspective, and there was no cost to learning the layout according to a
      nonegocentric axis. When the shape of the layout was bilaterally symmetric
      relative to the intrinsic axis of learning, novel headings orthogonal to that
      axis were retrieved more accurately than were other novel headings. These results
      indicate that spatial memories are defined with respect to intrinsic frames of
      reference, which are selected on the basis of egocentric experience and
      environmental cues.

PMID- 11827076
TI  - A reexamination of stimulus-frequency effects in recognition: two mirrors for low
      and high-frequency pseudowords.
AB  - The word-frequency mirror effect (more hits and fewer false alarms for low
      frequency than for high-frequency words) has intrigued memory researchers, and
      multiple accounts have been offered to explain the result. In this study,
      participants were differentially familiarized to various pseudowords in a
      familiarization phase that spanned multiple weeks. Recognition tests given during
      the first week of familiarization replicated a result of W. T. Maddox and W. K.
      Estes (1997) that failed to show the classic word-frequency mirror effect for
      pseudowords; however, recognition tests given toward the end of training showed
      the classic mirror pattern. In addition, a stimulus-frequency mirror effect for
      "remember" vs. "know" judgments was obtained. These data are consistent with an
      account of the mirror effect that posits the involvement of dual processes for
      episodic recognition.

PMID- 11827079
TI  - Semantic interference from objects both in and out of a scene context.
AB  - Prior studies have found that, despite the intentions of the participants,
      objects automatically activate their semantic representations; however, this
      research examined only objects presented in isolation without a background
      context. The present set of experiments examined the automaticity issue for
      objects presented in isolation as well as in scenes. In Experiments 1 and 2,
      words were categorized more slowly when they were embedded inside incongruent
      objects (e.g., the word chair in a picture of a duck) than inside neutral
      nonobjects, suggesting that the meanings of the objects were activated despite
      participants' intentions. A new interference task was introduced in Experiment 3.
      When the same objects and words from the first 2 experiments were inserted into
      scenes in which those objects were probable or improbable, interference occurred
      from probable pictured objects but not from improbable pictured objects.
      Implications for theories of automaticity and models of object identification are
      discussed.

PMID- 11827080
TI  - What exactly interacts with spelling-sound consistency in word naming?
AB  - Word frequency, age of acquisition (AoA), and imageability were combined with
      spelling-sound consistency, and their effects on word naming were examined.
      Frequency and AoA interacted with consistency (Experiments 1 and 2). Imageability
      did not (Experiment 3). Experiment 4 replicated Experiment 2 of E. Strain, K. E.
      Patterson, and M. S. Seidenberg's (1995) study and obtained the same apparent
      effect of imageability on naming. That effect disappeared when AoA was entered as
      a covariate. An explanation of the interactions of consistency with frequency and
      AoA is offered in terms of the properties of adaptive connectionist networks
      given gradual and cumulative training.

PMID- 11827081
TI  - Theories of word naming interact with spelling-sound consistency.
AB  - In a previous study (E. Strain, K. Patterson, & M. S. Seidenberg, 1995), the
      authors concluded that word naming is characterized by an interaction between
      spelling-sound typicality and word imageability, thus implicating a role for word
      meaning in the naming process. J. Monaghan and A. W. Ellis (2002) reject E.
      Strain et al.'s conclusion, arguing that it is age of acquisition (AoA) and not
      imageability that interacts with spelling-sound typicality. In this article, the
      authors question their alternative interpretation (a) by raising a number of
      conceptual and methodological issues germane to this debate and (b) by presenting
      new data that confirm a significant interaction between spelling-sound typicality
      and imageability in word-naming latencies, an interaction that is reliable when
      word AoA is controlled in a regression analysis.

PMID- 11827082
TI  - Processing picture-word stimuli: the contingent nature of picture and of word
      superiority.
AB  - Participants named (Experiments 1-2) or categorized (Experiments 3-4) the picture
      or the word of picture-word compounds that varied in the relative saliency of the
      2 components and in the correlation between them over the experimental trials.
      Picture-word interference (PWI) was gauged through Stroop and Garner effects. PWI
      was found to be malleable; its magnitude and very presence depending lawfully on
      the contextual variations introduced. The contingent nature of PWI is a fact to
      be reckoned with by theorists of picture-word processing.

PMID- 11827083
TI  - The activation of word class information during speech production.
AB  - In 5 picture-word interference experiments the activation of word class
      information was investigated. The first experiment, in which subjects used bare
      nouns to describe the pictures, failed to reveal any interference effect of noun
      distractor words as opposed to closed-class distractor words. In the next 4
      experiments the pictures were named by using a definite determiner and the noun
      completing a sentence fragment. The data demonstrate that noun distractors
      interfere more strongly with picture naming than do non-noun distractors. This
      held for both visual and auditory presentation of the distractor words. The
      interference effect showed up in a time window where semantic interference can
      usually be observed, supporting the assumption that at an early stage of lexical
      access semantic and syntactic activation processes overlap.

PMID- 11827084
TI  - Discrepancies between orthographic and unrelated baselines in masked priming
      undermine a decompositional account of morphological facilitation.
AB  - This study uses the masked priming procedure to compare the decompositionality of
      regular with irregular English past tense forms relative to both an unrelated
      baseline and a baseline matched on orthographic similarity to the morphological
      prime. Morphological facilitation varies with the degree of similarity between
      related primes and targets. Discrepancies between unrelated and orthographic
      baselines arise when prime and target match in length and form overlap is high.
      The outcome demonstrates the key role of baselines in assessments of
      morphological facilitation and highlights problems of interpretation when
      evidence of morphological decomposition depends on meeting a statistical
      criterion for significant morphological facilitation.

PMID- 11827085
TI  - Sublexical or lexical effects on serial recall of nonwords?
AB  - S. E. Gathercole, C. R. Frankish, S. J. Pickering, and S. Peaker (1999) reported
      2 experiments in which they manipulated phonotactic properties of nonword stimuli
      and observed the effects on serial recall. Their results show superior recall for
      items consisting of more frequent phoneme pairs (biphone frequency). Biphone
      frequency was counted as the number of 3 phoneme words in which the phoneme pair
      occurs. In the first experiment of the current article, the authors made the same
      manipulation while controlling for the number of lexical neighbors and found no
      effect of biphone frequency. In the second experiment, the authors manipulated
      neighborhood size while controlling biphone frequency and found a significant
      effect of neighborhood size. The authors argued that serial recall of nonwords is
      influenced by lexical rather than sublexical knowledge.

PMID- 11827086
TI  - In search of perceptual influences of sentence context on word recognition.
AB  - A major issue in the study of word perception concerns the nature (perceptual or
      nonperceptual) of sentence context effects. The authors compared effects of
      legal, word replacement, nonword replacement, and transposed contexts on target
      word performance using the Reicher-Wheeler task to suppress nonperceptual
      influences of contextual and lexical constraint. Experiment 1 showed superior
      target word performance for legal (e.g., "it began to flap/flop") over all other
      contexts and for transposed over word replacement and nonword replacement
      contexts. Experiment 2 replicated these findings with higher constraint contexts
      (e.g., "the cellar is dark/dank") and Experiment 3 showed that strong constraint
      contexts improved performance for congruent (e.g., "born to be wild") but not
      incongruent (e.g., mild) target words. These findings support the view that the
      very perception of words can be enhanced when words are presented in legal
      sentence contexts.

PMID- 11827088
TI  - Are performance predictions for text based on ease of processing?
AB  - In 4 experiments, the authors evaluated the hypothesis that performance
      predictions for text are based on ease of processing. In each experiment,
      participants read texts, predicted their performance for each one, and then were
      tested. Ease of processing was manipulated by having participants read texts that
      varied in coherence. Coherence was varied by manipulating causal relatedness
      across sentence pairs (Experiments 1 and 2) and by altering the structure of
      sentences within paragraphs (Experiment 3). In these experiments, prediction
      magnitudes increased as coherence increased, suggesting that predictions were
      based on processing ease. In Experiment 4, prediction magnitudes were greater for
      intact paragraphs than for paragraphs with letters deleted from some of the
      words. Discussion focuses on resolving apparent inconsistencies in the literature
      concerning whether processing ease influences performance predictions.

PMID- 11827087
TI  - Processing of logically valid and logically invalid conditional inferences in
      discourse comprehension.
AB  - Two competing theories of processing of conditionals (if-then) were tested.
      Syntactic theories posit that people only draw inferences conforming to the
      logically valid modus ponens (MP) schema. Mental models theories predict that
      people draw MP and invalid affirming-the-consequent (AC) inferences. Three
      experiments tested these predictions. Participants read short stories that
      conformed to either the MP or AC form but without conclusions, and they completed
      either priming or recognition tasks. Results indicate that both MP and AC
      inferences occur during discourse processing: MP and AC premise forms prime their
      respective conclusions, participants erroneously judged that they had read the
      conclusions to MP and AC arguments, and AC inferences did not stem from a
      biconditional interpretation of conditionals. Findings support mental models
      theories.

PMID- 11827089
TI  - Analogical problem solving: a hierarchical analysis of procedural similarity.
AB  - Similarity between source analogues and target problems is a central theme in the
      research on analogical transfer. Much of the theorizing and research has focused
      on the effects of superficial and structural similarity on transfer. The present
      research is an attempt to analyze systematically another critical type of
      similarity, namely, procedural similarity, and to examine its effects on the
      executing process. Participants viewed a schematic picture as a source model,
      interpreted its conceptual meaning, and then attempted to solve a problem to
      which the conceptual information from the source model could be applied. The
      results indicate that the ease with which a source solution was implemented was
      largely determined by the abstraction level at which a solution was shared by a
      source analogue and the target problem. The degree of procedural similarity was
      also found to influence the executing process in analogical transfer. A
      conceptual model concerning the function of procedural similarity as a
      utilizational constraint in analogical problem solving is proposed.

PMID- 11827090
TI  - Learning and attention in multidimensional identification and categorization:
      separating low-level perceptual processes and high-level decisional processes.
AB  - Four observers completed identification and categorization tasks. Learning and
      attention processes were examined by applying general recognition theory (F. G.
      Ashby & J. T. Townsend, 1986), which separates perceptual, decisional, and
      attentional processes. Learning led to decision regions that became more nearly
      optimal. Learning had little effect on perceptual processes in identification and
      decisional integration categorization tasks but affected perceptual processes in
      decisional selective attention categorization tasks, leading to perceptual
      selective attention. These findings suggest that (a) identification and
      categorization invoke decision strategies that are localized in the striatum (F.
      G. Ashby, E. M. Waldron, W. W. Lee, & A. Berkman, 2001) and (b) perceptual and
      decisional attention systems exist and are mediated by distinct brain structures
      (M. I. Posner & S. E. Petersen, 1990).

PMID- 11827091
TI  - Introduction to the Special Issue on Normal Neuropsychological Development in the
      School-Age Years.
AB  - In neuropsychological research on normal development relatively little interest
      has been devoted to age-related changes in school age. This is surprising in
      light of the significance of the changes that take place in this period of life,
      the availability of normative data, and the ongoing research on neural
      development. The studies included in this issue take a closer look at normative
      data from school-age children of various ages in performances of attention,
      language, sensorimotor functions, perceptual functions, memory and learning, and
      functional asymmetries. A finding evident in many of the studies is that age
      effects seem to be more accentuated below 9 to 10 years than after that age. It
      is hoped that this special issue will draw attention to the scarcity of data in
      this realm and to the possibilities of utilizing existing databases for study on
      normal development in school age.

PMID- 11827092
TI  - Effects of age on neurocognitive measures of children ages 5 to 12: a cross
      sectional study on 800 children from the United States.
AB  - The standardization of the NEPSY-A Developmental Neuropsychological Assessment
      (Korkman, Kirk, & Kemp, 1998) provided an opportunity to study the effects of age
      across the age range 5 to 12 years. Test scores of 800 children on 20 subtests of
      NEPSY were analyzed. These measures are based on traditions of neuropsychological
      assessment and are thought to reflect attention and executive functions,
      language, sensorimotor functions, visuospatial functions, and memory and
      learning. The effects of age were very significant on all measures, confirming
      the developmental sensitivity of the NEPSY. The effects of age were more
      significant in the 5- to 8-year age range than in the 9- to 12-year range. Only
      performance on tasks of fluency and memory span for sentences showed significant
      age effects in the 10- to 12-year age range. This suggests that neurocognitive
      development is rapid in the 5- to 8-year age range and more moderate in the 9- to
      12-year age range.

PMID- 11827093
TI  - Neuropsychological test scores, academic performance, and developmental disorders
      in Spanish-speaking children.
AB  - Limited information is currently available about performance of Spanish-speaking
      children on different neuropsychological tests. This study was designed to (a)
      analyze the effects of age and sex on different neuropsychological test scores of
      a randomly selected sample of Spanish-speaking children, (b) analyze the value of
      neuropsychological test scores for predicting school performance, and (c)
      describe the neuropsychological profile of Spanish-speaking children with
      learning disabilities (LD). Two hundred ninety (141 boys, 149 girls) 6- to 11
      year-old children were selected from a school in Bogota, Colombia. Three age
      groups were distinguished: 6- to 7-, 8- to 9-, and 10- to 11-year-olds.
      Performance was measured utilizing the following neuropsychological tests:
      Seashore Rhythm Test, Finger Tapping Test (FTT), Grooved Pegboard Test,
      Children's Category Test (CCT), California Verbal Learning Test-Children's
      Version (CVLT-C), Benton Visual Retention Test (BVRT), and Bateria Woodcock
      Psicoeducativa en Espanol (Woodcock, 1982). Normative scores were calculated. Age
      effect was significant for most of the test scores. A significant sex effect was
      observed for 3 test scores. Intercorrelations were performed between
      neuropsychological test scores and academic areas (science, mathematics, Spanish,
      social studies, and music). In a post hoc analysis, children presenting very low
      scores on the reading, writing, and arithmetic achievement scales of the Woodcock
      battery were identified in the sample, and their neuropsychological test scores
      were compared with a matched normal group. Finally, a comparison was made between
      Colombian and American norms.

PMID- 11827094
TI  - Performance of Zambian children on the NEPSY: a pilot study.
AB  - Forty-five literate schoolchildren aged 9 (n = 25) and 11 (n = 20) from urban
      Zambia were given core and expanded tests on the NEPSY and their performance was
      scored according to age-equivalent norms for U.S. children. This study indicates
      that in urban, literate Zambian children, the NEPSY is relatively insensitive to
      language and cultural influences that often compromise the applicability of
      Western tests in the developing world. No consistent improvement in the standard
      scores was found as a function of educational experience. Comparison against the
      U.S. normative average revealed that both age groups were poorer in the domains
      of language and attention and executive functions, whereas their performance was
      better in the visuospatial processing domain. It is concluded that the NEPSY in
      its present form may be clinically useful, but its results should still be
      treated with caution, taking into account cultural, language, and personal
      demographic information. More studies, with divergent and larger samples of
      varying age ranges are required. It seems that the NEPSY could serve as the
      initial step in the development of neuropsychological practices in Zambia.

PMID- 11827095
TI  - Development of executive functions through late childhood and adolescence in an
      Australian sample.
AB  - Although there have been significant theoretical advances in the field of child
      neuropsychology, developmental features of adolescence have received less
      attention. Progress in clinical practice is restricted due to a lack of well
      standardized, developmentally appropriate assessment techniques. This article
      addresses these issues in relation to executive skills. These abilities are
      targeted for 2 reasons: first, because they are often considered to be mature
      during late childhood and adolescence, despite limited investigation in this age
      range; and second, because of their central importance to efficient day-to-day
      functioning. Using a normative sample of 138 children, aged 11.0 to 17.11 years,
      this article plots the development of executive skills through late childhood and
      early adolescence and interprets progress in these skills with reference to
      current neurological and cognitive theory.

PMID- 11827096
TI  - Differential development of attention and executive functions in 3- to 12-year
      old Finnish children.
AB  - The developmental sequence of attention and executive functions (EFs) was studied
      by utilizing normative data from four hundred 3- through 12-year-old Finnish
      children. Data from 10 subtests measuring impulse control and inhibition of
      irrelevant responses, auditory and visual attention, visual search, planning, and
      verbal and visual fluency were included. The development proceeded sequentially,
      from motor inhibition and impulse control to functions of selective and sustained
      attention, and finally to EFs of fluency. Significant relations between gender
      and development and between parent education and development were found in
      several subtests. In a factor analysis, inhibition, auditory attention, visual
      attention, and the EF of fluency clustered into separate factors. The
      developmental staging and clustering of functions suggests that, although
      inhibition, attention, and EFs are highly interrelated cognitive functions, their
      developmental sequences are separate from one another. The development of basic
      inhibitory functions precedes the development of more complex functions of
      selective attention, and EFs continue to develop into adolescence.

PMID- 11827097
TI  - Lateralities in normal children ages 3 to 8 and their role in cognitive
      performances.
AB  - The presence and type of correlations between laterality and cognitive skills in
      normal adults or children remains controversial. This study examines relations
      between different lateralities, that is, handedness, footedness, eyedness,
      parental left-handedness, asymmetry of hand skill on a computerized version of
      the Peg-Moving Task (CPMT) proposed by Annett (1985), and different verbal and
      non-verbal skills assessed by 13 tasks in 254 normal children, aged 3 to 8 years.
      Results showed increasing performances with increasing dextrality on the CPMT for
      2 tasks involving phonology (Phonological Fluency and Reading Nonwords), 2 tasks
      involving visual memory and visuospatial skills, and for finger localization.
      Footedness, eyedness, and parental left-handedness had no significant effect on
      cognitive performance. The pattern of performance according to the sinistrality
      dextrality continuum was highly variable from one cognitive task to the other.
      The previously mentioned results suggest that relative hand skill is a better
      correlative of cognitiveperformance than the usual measures of handedness.
      Further study is needed to specify the pattern of associations.

PMID- 11827098
TI  - Age effects in dichotic listening to consonant-vowel syllables: interactions with
      attention.
AB  - A relatively large sample of individuals (N = 240) ranging from 7 to 70 years
      were studied with the dichotic listening (DL) technique as a measure of language
      lateralization. Two questions were asked: (a) Is there a developmental effect for
      the right-ear advantage (REA) with age? (b) Is there a developmental effect for
      attentional modulation of the REA? The participants were all right-handed,
      healthy individuals tested in Sweden and Norway. The stimuli were dichotic
      presentations of consonant-vowel (CV) syllable pairs. There were 3 different
      attentional conditions: nonforced (NF) attention, with no specific instructions
      about focusing of attention; forced-right (FR) attention, with instructions to
      focus attention on the right-ear stimulus; and forced-left (FL) attention, with
      instructions to focus attention on the left-ear stimulus. The results showed a
      REA in all age groups, except for the 9-year-olds, in the NF condition. In the FR
      condition, all age groups showed a REA. The youngest age groups did not, however,
      increase the REA to the same degree as the older age groups, as indicated by the
      significant age x ear interaction. In the FL condition, all age groups, with the
      exception of the youngest groups, showed a left-ear advantage (LEA). It is
      concluded that the REA effect in DL is subject to developmental effects and that
      attentional effects on laterality also develop with increasing age.

PMID- 11827099
TI  - Immunogold localization of RNA polymerase II and pre-mRNA splicing factors in
      Tenebrio molitor oocyte nuclei with special emphasis on karyosphere development.
AB  - Ultrastructural and immunomorphological characteristics of the developing
      karyosphere and extrachromosomal nuclear bodies (NBs) in Tenebrio molitor oocytes
      are presented. Three consecutive stages of karyosphere development were
      identified: reticular, compact and ring-shaped. At the beginning of the
      karyosphere development (reticular and compact stages), condensed chromosomes are
      associated with a fibrogranular material (FGM). The successive karyosphere
      development is accompanied by the reorganization of FGM into fibrogranular NBs.
      Special attention was given to the nuclear distribution of hyperphosphorylated
      and non-phosphorylated forms of RNA polymerase II (pol II) and pre-mRNA splicing
      factors (snRNPs and SC35 protein) during karyosphere development and NB
      formation. The immunoelectron microscopy revealed that two forms of pol II and
      splicing factors being assembled in FGM are deposited in appropriate NBs. Some
      NBs were also shown to contain coilin, a marker protein for Cajal (coiled)
      bodies. We suggest that different types of NBs appearing in T. molitor oocyte
      nuclei along with the cessation of transcriptional activity during the
      karyosphere development represent storage domains for inactive RNA
      transcription/processing machinery to later usage in early embryogenesis.

PMID- 11827100
TI  - Sites of lanthanum occlusion in the testis of the crayfish Procambarus
      paeninsulanus (Crustacea: Cambaridae).
AB  - The presence of stage-dependent occlusive junctions between adjacent Sertoli
      cells in the seminiferous epithelium of the crayfish testis was demonstrated by a
      lanthanum tracer study. The germinal epithelium did not appear to be
      compartmentalized, as evidenced by access of lanthanum to spermatogonia,
      spermatocytes, and spermatids. During late spermiogenesis, when encapsulated
      stage VI spermatids were concentrated in the center of an acinus, lanthanum was
      excluded apically, coincident with lumen formation. This is the first study
      examining occluding junctions using a barrier penetration method in the testis of
      a crustacean.

PMID- 11827101
TI  - Cell surface phenotype and cytokine secretion in Caco-2 cell cultures: increased
      RANTES production and IL-2 transcription upon stimulation with IL-1beta.
AB  - Caco-2 is a colonic tumour cell line which, when cultured, spontaneously exhibits
      enterocyte-like characteristics. Given the difficulties in maintaining long
      lasting cultures of enterocytes, this cell line may be a suitable in vitro model
      to carry out experiments trying to delineate the involvement of enterocytes in
      local immune responses, and their role in pathology. It seems then reasonable to
      obtain a detailed immune analysis of Caco-2, and compare it with available data
      on enterocytes. Cytofluorometry revealed several leukocyte markers on Caco-2,
      present also on human enterocytes. These markers include surface proteases (CD10,
      CD13 and CD26), antigen-presenting cell markers (CD13, CD14, CD35 and CD63),
      integrins (CD18 and CD61), epithelial/endothelial markers (CD21, CD31, CD47 and
      CD59) and finally, CD25 and CD28. In contrast to enterocytes, HLA-class 11
      molecules are not found on Caco-2, whether resting or gamma-IFN-stimulated.
      Moreover, culture experiments with allogeneic lymphocytes revealed that Caco-2
      cells were unable to induce their proliferation. Cytokine analysis showed an
      increased RANTES synthesis and IL-2 transcription upon stimulation with IL-1beta.
      Finally, amongst RANTES receptors, CCR1 is found on Caco-2 cells, whereas CCR3
      and CCR5 are not.

PMID- 11827102
TI  - The serosa of Manduca sexta (Insecta, Lepidoptera): ontogeny, secretory activity,
      structural changes, and functional considerations.
AB  - In Manduca sexta, the blastoderm forms successively and becomes immediately
      cellularized as the cleavage energids reach the surface of the oocyte.
      Presumptive serosal cells are large and contain 2 or 4 large polyploid nuclei;
      presumptive embryonic cells are small and mononuclear. All parts of the
      blastoderm participate in the uptake and digestion of yolk material. About 10 h
      post-oviposition, the blastoderm breaks at the amnioserosal fold and the
      extraembryonic part closes above the germ band and constitutes the serosa (12 h
      post-oviposition, i.e. 10% development completed). At once, the serosa starts to
      secrete a cuticle consisting of an epi- and a lamellated endocuticle. Detachment
      of the serosal cuticle, 22h post-oviposition, is reminiscent of apolysis of
      larval cuticle. Thereafter, the serosa deposits a membranous structure, the
      serosal membrane. The sercretory process lasts from 23h to 44h post-oviposition.
      At first a fine granular layer, then an amorphous, spongy-like, fibrillar layer
      is secreted via microvilli. This persisting membrane is tough, rubbery and very
      elastic. It may serve to bolster the serosa during katatrepsis (48h post
      oviposition) and later embryonic movements. After detachment of the serosal
      membrane, 44h post-oviposition, a distinct subcellular reorganization of the
      serosa takes place. The nuclei become still larger and more irregular. Uptake of
      yolk granules, but not of lipid droplets, ceases, although interaction of serosa
      and yolk cells are intense. Serosal cells include many mitochondria, large areas
      of rER, besides some sER, increasing amounts of lysosomal bodies and prominent
      Golgi complexes. Most conspicuous is the assembly of spindle-shaped, electron
      lucent vesicles below the apical surface. These vesicles may contain metabolic
      products which are released into the peripheral space. The studies show that the
      serosa assumes changing functions during embryogenesis: digestion of yolk
      substances, synthesis of a serosal cuticle and a serosal membrane, which may have
      a protective function, and excretion.

PMID- 11827104
TI  - Binucleate and biflagellate spermatozoa in Tricholepidion gertschi Wygodzynsky
      (Insecta, Zygentoma).
AB  - The phenomenon of sperm pairing is known from some species of the apterygotan
      insect order Zygentoma, and has been described as the close apposition of two
      sperm cells. When released from the testes, they are single cells; pairing taking
      place in the deferent ducts. In a study of the relic species Tricholepidion
      gertschi, Zygentoma, sperm pairing was found to be due to a true fusion of two
      partners along their entire sperm head regions. The spermatozoon thus formed has
      two acrosomes, two nuclei and two separate sperm tails. The biflagellate
      spermatozoon swims with coordinated movements of its two flagella only when the
      two flagella lie close together but is totally uncoordinated when separate. The
      spermatozoon is about 50 microm long, thus much shorter than those of related
      apterygotan species. The mechanism of sperm cell fusion is unclear, although it
      appears that a 55-nm wide layer of electron dense substance, here termed the
      peripheral lamina, may play a role in delimiting the extent of sperm fusion.

PMID- 11827103
TI  - Sperm ultrastructure and spermiogenesis in the relic species Tricholepidion
      gertschi Wygodzinsky (Insecta, Zygentoma).
AB  - The silverfish Tricholepidion gertschi is of interest in that it is the most
      basal representative of Zygentoma. An ultrastructural study of its spermiogenesis
      was performed to find out whether there are traits which resemble those of other,
      more advanced insects. This was found to be the case; spermiogenesis can be
      considered to be of a common insectan type, leading to the formation of elongated
      sperm cells with acrosome, nucleus, neck region and a tail with axoneme and two
      mitochondrial derivatives. Total cell length, 50 microm, is short for an insect.
      There are some specializations, which probably represent autapomorphies. The
      acrosome has a posterior canal or cleft that makes a U-turn. The centriole
      adjunct forms a prominent post-nuclear ring surrounding the centriole and have a
      posterior extension, and further originates nine intertubular fibers with a
      longitudinal periodicity and two accessory bodies. The mitochondrial derivatives
      have five rows of regularly spaced cristae within a crystalline matrix. The
      axoneme has accessory tubules consisting of 16 protofilaments, formed at the B
      tubules of the doublets and placed at some distance from them in the posterior
      part of the sperm tail.

PMID- 11827106
TI  - The main issues affecting coasts of the Indian and western Pacific Oceans: a meta
      analysis from Seas at the Millennium.
AB  - A review of the world oceans in three volumes by 365 scientists, provides scope
      for several 'meta-analyses' of the main problems affecting over 100 areas in the
      year 2000. This article summarises the main issues affecting a sub-set of the
      reviewed areas, covering Asian, African and Arabian countries dealt with in
      Volume 2, which included over 50 articles. From all issues raised, assessment is
      made of the nature of the major ones, including evaluation of reasons why so many
      of them remain important issues after so much attention to them. These include
      long standing problems, several problems more newly flagged as becoming
      particularly important, the issue of global warming and no less than three
      related issues connected with fishing and over exploitation. One or two issues
      such as industrial pollution and sewage, previously considered of almost
      universal concern, almost traditional pollution issues even, continue to feature
      strongly for some countries, but while these were almost always referred to in
      Seas chapters, by and large these categories appear not to be the most pressing
      of issues today, except in localized areas (albeit areas where huge numbers of
      people live). Perhaps other issues have simply taken over. They are excluded from
      this article.

PMID- 11827105
TI  - Postnatal growth of the rat palatine gland.
AB  - To elucidate how the palatine glands grow postnatally, the palatine glands of
      rats from 0 to 8 weeks of age were investigated histologically and
      immunohistochemically. Under light microscope, three dimensions of the right part
      of the palatine glands were measured and the total number of excretory ducts of
      the glands was counted from the parasagittal serial sections.
      Immunohistochemistry with anti-5-bromo-2'-deoxyuridine (BrdU) monoclonal antibody
      was also employed to detect the cellular proliferative activity. At birth (0
      weeks), the palatine glands consisted of ducts and immature acini. The ducts in
      the glands were connected with excretory ducts. After 2 weeks, there was no duct
      in the glands. Most acinar cells became mature as mucous cells and took the form
      of tubulo-acini connected directly with excretory ducts. In the posterior region
      of the glands, serous acinar cells forming demilunes were occasionally seen. All
      three dimensions of the palatine glands became longer, and the number of
      excretory ducts tended to increase. Immunohistochemistry showed acinar and duct
      cells were highly proliferative in early stage of postnatal life and their
      proliferative activity decreased thereafter. This study demonstrated that
      immature rat palatine glands of newborn rats grow three-dimensionally during
      maturation, and that the parenchymal cell proliferation contributes to the growth
      of the rat palatine glands. In addition, it is suggested that the glandular
      tissue arises from the excretory ducts formed postnatally.

PMID- 11827107
TI  - St. Vincent and the Grenadines.
AB  - Saint Vincent and the Grenadines conjures up images of a yachting haven and a
      quiet tourists' paradise. The conflicting demands of a growing population, a
      middle-income economy dominated by fishing, plantation agriculture and tourism,
      and environmental and social concerns, all contribute to marine stress on the
      limited, precious, but internationally important resources. While the vision
      exists to manage effectively coastal and offshore resources, the institutional,
      financial and social capital to achieve that vision is limited. Development of
      the fledgling partnerships between local communities, national governmental
      structures and the international research, government and donor organisations
      seems the best hope to conserve the environment and coastal livelihoods of the
      islands.

PMID- 11827108
TI  - Honduras: Caribbean Coast.
AB  - The coast of Honduras, Central America, represents the southern end of the
      Mesoamerican Barrier Reef System, although its marine resources are less
      extensive and studied than nearby Belize and Mexico. However, the coastal zone
      contains mainland reef formations, mangroves, wetlands, seagrass beds and
      extensive fringing reefs around its offshore islands, and has a key role in the
      economy of the country. Like most tropical areas, this complex of benthic
      habitats experiences limited annual variation in climatic and oceanographic
      conditions but seasonal and occasional conditions, particularly coral bleaching
      and hurricanes, are important influences. The effects of stochastic factors on
      the country's coral reefs were clearly demonstrated during 1998 when Honduras
      experienced a major hurricane and bleaching event. Any natural or anthropogenic
      impacts on reef health will inevitably affect other countries in Latin America,
      and vice versa, since the marine resources are linked via currents and the
      functioning of the system transcends political boundaries. Much further work on,
      for example, movement of larvae and transfer of pollutants is required to
      delineate the full extent of these links. Anthropogenic impacts, largely driven
      by the increasing population and proportion of people living in coastal areas,
      are numerous and include key factors such as agricultural run-off, over-fishing,
      urban and industrial pollution (particularly sewage) and infrastructure
      development. Many of these threats act synergistically and, for example, poor
      watershed management via shifting cultivation, increases sedimentation and
      pesticide run-off onto coral reefs, which increases stress to corals already
      affected by decreasing water quality and coral bleaching. Threats from
      agriculture and fishing are particularly significant because of the size of both
      industries. The desire to generate urgently required revenue within Honduras has
      also led to increased tourism which provides an overarching stress to marine
      resources since most tourists spend time in the coastal zone. Hence the last
      decade has seen a dramatic increase in coastal development, a greater requirement
      for sewage treatment and more demand for freshwater, particularly in the Bay
      Islands. Although coastal zone management is relatively recent in Honduras, it is
      gaining momentum from both large-scale initiatives, such as the Ministry of
      Tourism's 'Bay Islands Environmental Management Project', and national and
      international NGO projects. For example, a series of marine protected areas and
      legislative regulations have been established, but management capacity,
      enforcement and monitoring are limited by funding, expertise and training.
      Existing and future initiatives, supported by increased political will and
      environmental awareness of stakeholders, are vital for the long-term economic
      development of the country.

PMID- 11827109
TI  - South China Sea.
AB  - The South China Sea is poorly understood in terms of its marine biota, ecology
      and the human impacts upon it. What is known is most often contained in reports
      and workshop and conference documents that are not available to the wider
      scientific community. The South China Sea has an area of some 3.3 million km2 and
      depths range from the shallowest coastal fringe to 5377 m in the Manila Trench.
      It is also studded with numerous islets, atolls and reefs many of which are just
      awash at low tide. It is largely confined within the Tropic of Cancer and,
      therefore, experiences a monsoonal climate being influenced by the Southwest
      Monsoon in summer and the Northeast Monsoon in winter. The South China Sea is a
      marginal sea and, therefore, largely surrounded by land. Countries that have a
      major influence on and claims to the sea include China, Malaysia, the Philippines
      and Vietnam, although Thailand, Indonesia and Taiwan have some too. The coastal
      fringes of the South China Sea are home to about 270 million people that have had
      some of the fastest developing and most vibrant economies on the globe.
      Consequently, anthropogenic impacts, such as over-exploitation of resources and
      pollution, are anticipated to be huge although, in reality, relatively little is
      known about them. The Indo-West Pacific biogeographic province, at the centre of
      which the South China Sea lies, is probably the world's most diverse shallow
      water marine area. Of three major nearshore habitat types, i.e., coral reefs,
      mangroves and seagrasses, 45 mangrove species out of a global total of 51, most
      of the currently recognised 70 coral genera and 20 of 50 known seagrass species
      have been recorded from the South China Sea. The island groups of the South China
      Sea are all disputed and sovereignty is claimed over them by a number of
      countries. Conflicts have in recent decades arisen over them because of perceived
      national rights. It is perhaps because of this that so little research has been
      undertaken on the South China Sea. What data are available, however, and if Hong
      Kong is used, as it is herein, as an indicator of what the perturbations of other
      regional cities upon the South China Sea are like, then it is impacted grossly
      and an ecological disaster has probably already, but unknowingly, happened.

PMID- 11827110
TI  - Kenya.
AB  - The Kenya coast is bathed by the northward-flowing warm waters of the East Africa
      Coastal Current, located between latitudes 1 and 5 degrees S. With a narrow
      continental shelf, the coastal marine environments are dominated by coral reefs,
      seagrass beds and mangroves, with large expanses of sandy substrates where river
      inputs from Kenya's two largest rivers, the Tana and Athi rivers, prevent the
      growth of coral reefs. The northern part of the coast is seasonally influenced by
      upwelling waters of the Somali Current, resulting in lower water temperatures for
      part of the year. The coast is made up of raised Pleistocene reefs on coastal
      plains and hills of sedimentary origin, which support native habitats dominated
      by scrub bush and remnant pockets of the forests that used to cover East Africa
      and the Congo basin. The marine environment is characterized by warm tropical
      conditions varying at the surface between 25 degrees C and 31 degrees C during
      the year, stable salinity regimes, and moderately high nutrient levels from
      terrestrial runoff and groundwater. The semi-diurnal tidal regime varies from 1.5
      to 4 m amplitude from neap to spring tides, creating extensive intertidal
      platform and rocky-shore communities exposed twice-daily during low tides.
      Fringing reef crests dominate the whole southern coast and parts of the northern
      coast towards Somalia, forming a natural barrier to the wave energy from the
      ocean. Coral reefs form the dominant ecosystem along the majority of the Kenya
      coast, creating habitats for seagrasses and mangroves in the lagoons and creeks
      protected by the reef crests. Kenya's marine environment faces a number of
      threats from the growing coastal human population estimated at just under three
      million in 2000. Extraction of fish and other resources from the narrow
      continental shelf, coral reef and mangrove ecosystems increases each year with
      inadequate monitoring and management structures to protect the resource bases.
      Coastal development in urban and tourist centers proceeds with little regard for
      environmental and social impacts. With a faltering economy, industrial
      development in Mombasa proceeds with few checks on pollution and other impacts.
      In 1998 Kenya's coral reefs suffered 50-80% mortality from the El Nino-related
      coral bleaching event that affected the entire Indian Ocean. The institutional,
      human resource and legal infrastructure for managing the coastal environment has
      in the past been low, however these are rapidly improving with the revitalization
      of national institutions and the passing in 1999 of an Environment Act. Marine
      Protected Areas are the key tool currently used in management of marine
      ecosystems, and focus principally on coral reefs and biodiversity protection. New
      initiatives are underway to improve application of fisheries regulations, and to
      use Integrated Coastal Area Management (ICAM) as a framework for protecting
      marine and coastal environments.

PMID- 11827111
TI  - How toxic is toxic?

PMID- 11827112
TI  - England's beaches improve...UK rivers and estuaries not so bad either.

PMID- 11827113
TI  - Australia protects world's largest living fish.

PMID- 11827114
TI  - Seabirds at risk around offshore oil platforms in the north-west Atlantic.
AB  - Seabirds aggregate around oil drilling platforms and rigs in above average
      numbers due to night lighting, flaring, food and other visual cues. Bird
      mortality has been documented due to impact on the structure, oiling and
      incineration by the flare. The environmental circumstances for offshore
      hydrocarbon development in North-west Atlantic are unique because of the harsh
      climate, cold waters and because enormous seabird concentrations inhabit and move
      through the Grand Banks in autumn (storm-petrels, Oceanodroma spp), winter
      (dovekies, Alle alle, murres, Uria spp), spring and summer (shearwaters, Puffinus
      spp). Many species are planktivorous and attracted to artificial light sources.
      Most of the seabirds in the region are long-distance migrants, and hydrocarbon
      development in the North-west Atlantic could affect both regional and global
      breeding populations. Regulators need to take responsibility for these
      circumstances. It is essential to implement comprehensive, independent arm's
      length monitoring of potential avian impacts of offshore hydrocarbon platforms in
      the North-west Atlantic. This should include quantifying and determining the
      nature, timing and extent of bird mortality caused by these structures. Based on
      existing evidence of potential impacts of offshore hydrocarbon platforms on
      seabirds, it is difficult to understand why this has not been, and is not being,
      systematically implemented.

PMID- 11827115
TI  - Levels of organochlorine pesticide residues in some organs of the Ganges perch,
      Lates calcarifer, from the Ganges-Brahmaputra-Meghna Estuary, Bangladesh.
AB  - Levels of organochlorine pesticide residues (p,p' DDT, DDD, DDE, Aldrin,
      Dieldrin, Lindane, Heptachlor and BHC) were analysed in the dry and wet seasons
      in four organs (muscle, liver, gut and egg samples) of Ganges Perch, Lates
      calcarifer, collected during October-November-December, 1996 and May-June-July,
      1997 from the Ganges-Brahmaputtra-Meghna estuary. The residues were analysed by
      using gas-chromatography (GC) in electron capture detector (ECD) mode and were
      verified by thin layer chromatography (TLC). Among the four organs analysed, the
      residues were found in the order egg > gut > muscle > liver. The pesticide
      residues were found in the order sigmaDDT > Heptachlor > Dieldrin > Aldrin.
      Higher levels of residues were found during the dry season due to high lipid
      content in fishes. A positive correlation was observed between the pesticide
      residues (sigmaDDT and sigmaOCs) and lipid contents of fish, and the correlation
      was found to be linear. The concentrations of pesticide residues in muscle, liver
      and gut were below the FAO/WHO (1993) recommended permissible limit except in
      eggs.

PMID- 11827116
TI  - A comparison of plastic and plankton in the north Pacific central gyre.
AB  - The potential for ingestion of plastic particles by open ocean filter feeders was
      assessed by measuring the relative abundance and mass of neustonic plastic and
      zooplankton in surface waters under the central atmospheric high-pressure cells
      of the North Pacific Ocean. Neuston samples were collected at 11 random sites,
      using a manta trawl lined with 333 u mesh. The abundance and mass of neustonic
      plastic was the largest recorded anywhere in the Pacific Ocean at 334271 pieces
      km2 and 5114 g km2, respectively. Plankton abundance was approximately five times
      higher than that of plastic, but the mass of plastic was approximately six times
      that of plankton. The most frequently sampled types of identifiable plastic were
      thin films, polypropylene/monofilament line and unidentified plastic, most of
      which were miscellaneous fragments. Cumulatively, these three types accounted for
      99% of the total number of plastic pieces.

PMID- 11827117
TI  - Derelict fishing gear in the northwestern Hawaiian Islands: diving surveys and
      debris removal in 1999 confirm threat to coral reef ecosystems.
AB  - Marine debris threatens Northwestern Hawaiian Islands' (NWHI) coral reef
      ecosystems. Debris, a contaminant, entangles and kills endangered Hawaiian monk
      seals (Monachus schauinslandi), coral, and other wildlife. We describe a novel
      multi-agency effort using divers to systematically survey and remove derelict
      fishing gear from two NWHI in 1999. 14 t of derelict fishing gear were removed
      and debris distribution, density, type and fouling level documented at Lisianski
      Island and Pearl and Hermes Atoll. Reef debris density ranged from 3.4 to 62.2
      items/km2. Trawl netting was the most frequent debris type encountered (88%) and
      represented the greatest debris component recovered by weight (35%), followed by
      monofilament gillnet (34%), and maritime line (23%). Most debris recovered, 72%,
      had light or no fouling, suggesting debris may have short oceanic circulation
      histories. Our study demonstrates that derelict fishing gear poses a persistent
      threat to the coral reef ecosystems of the Hawaiian Archipelago.

PMID- 11827118
TI  - Hepatic 7-ethoxyresorufin O-deethylase activity in eel (Anguilla anguilla) from
      the Thames Estuary and comparisons with other United Kingdom Estuaries.
AB  - Hepatic microsomal 7-ethoxyresorufin O-deethylase (EROD) activities (indicative
      of exposure to polycyclic aromatic hydrocarbons (PAHs) and polychlorobiphenyls
      (PCBs)) were measured in eel Anguilla anguilla from the Thames Estuary. Fish were
      collected from up to 13 sites during November 1997, May and August 1998 and
      October 1999. Throughout this period no clear seasonal variation could be
      identified at every site along the Thames. However, during the summer months,
      fish sampled from sites in the middle to the upper estuary (Woolwich, Greenhithe
      and West Thurrock) reported up to 3-fold higher EROD activities compared to sites
      either at the upper reaches (Richmond and Brentford) at the same time of the
      year, or fish sampled in winter, along the entire length of the estuary. A
      laboratory exposure experiment demonstrated a 3-fold elevation of EROD activity 2
      days after injection with beta-naphthoflavone (beta-NF). However, higher levels
      of activity could be determined in fish sampled from the Weston canal near the
      Merseyside. The lowest levels of A. anguilla EROD activity were observed in fish
      sampled from the upper reaches of the River Tamar, Devon, and were comparable to
      activities determined in fish from the Wear and Humber estuaries. A. anguilla
      sampled along the Thames, Tyne and Tees estuaries reported between 2.5- and 7
      fold higher EROD activities compared to fish collected from the Tamar. These
      results indicate that a low to moderate induction of A. anguilla CYP1A had
      occurred (indicative of low to moderate exposure to PAHs and planar PCBs) in fish
      collected from the Thames, Tyne, Wear, Tees, Humber and Tamar estuaries. However,
      the highest level of EROD activity was observed in fish from the Weston Canal
      (Merseyside).

PMID- 11827119
TI  - Persistent organochlorine residues and toxic evaluation of polychlorinated
      biphenyls in sharks from the Mediterranean Sea (Italy).
AB  - Persistent organochlorines such as polychlorinated biphenyls including coplanar
      congeners, DDT compounds and HCB were measured in different tissues (muscle,
      liver and eggs) of two Mediterranean shark species: namely Centrophorus
      granulosus and Squalus blainvillei. The concentrations of organochlorines in the
      tissues and organs of both species were in the order DDTs > PCBs > HCB. The
      highest values of DDTs, PCBs and HCB were found in liver followed by eggs and
      muscle. Among DDTs the compound found in greatest concentration was p,p'-DDE. The
      PCB profiles were dominated by congeners 138, 153, and 180. The isomers with
      higher TEQs values were non- and mono-ortho congeners than di-ortho ones in
      muscle, liver and eggs of both species. Among the non-ortho, PCB 126 was the
      major contributing individual to the total TEQs in both species.

PMID- 11827120
TI  - Marine debris and human impacts on sea turtles in southern Brazil.
AB  - Dead stranded sea turtles were recovered and examined to determine the impact of
      anthropogenic debris and fishery activities on sea turtles on the coast of Rio
      Grande do Sul State, Brazil. Esophagus/stomach contents of 38 juvenile green
      Chelonia mydas, 10 adults and sub-adults loggerhead Caretta caretta, and two
      leatherback Dermochelys coriacea turtles (adult or sub-adult) included plastic
      bags as the main debris ingested, predominated by white and colorless pieces. The
      ingestion of anthropogenic debris accounted for the death of 13.2% of the green
      turtles examined. Signs of damage over the body and carapace indicated that
      fishing activities caused the death of 13.6% (3/22) of loggerheads and 1.5%
      (1/56) of green turtles. Therefore, it appears that direct and indirect effects
      of fishing activities may pose a threat to these species in Brazilian waters.
      Other sources of plastic debris should be investigated as well as the direct
      impact of fisheries, especially bottom trawl and gill nets, in order to establish
      effective conservation action.

PMID- 11827121
TI  - Hydrocarbons in surface sediments from the Changjiang (Yangtze River) Estuary,
      East China Sea.
AB  - Sedimentary aliphatic (AH) and polycyclic aromatic hydrocarbons (PAHs) were
      studied in the Changjiang Estuary and the adjacent East China Sea. Total AH
      ranged from 2.20 to 11.82 microg g(-1) and consisted of n-alkanes and a dominant
      petroleum-related unresolved complex mixture (UCM). Within the n-alkanes,
      terrestrial plant wax compounds prevailed at nearly all stations. Of the PAHs,
      biogenic perylene dominated at stations receiving riverine inputs. Anthropogenic
      PAHs originating from combustion/pyrolysis processes varied from 17 to 157 ng g(
      1), while fossil PAH concentrations ranged from 42 to 187 ng g(-1). Both biogenic
      and anthropogenic hydrocarbons are primarily derived from riverine discharges and
      accumulate at shallow-water stations. Distinct phase associations lead,
      nevertheless, to different sedimentation patterns. Fossil PAHs are enhanced at
      offshore stations where they are introduced directly by shipping activities.
      Biomarker fingerprints ascribe their source to Chinese crude oils. The overall
      levels of anthropogenic hydrocarbons are low compared to relevant areas worldwide
      and reveal a low/moderate level of hydrocarbon pollution.

PMID- 11827122
TI  - Iodine-129 concentrations in marginal seas of the north Pacific and Pacific
      influenced waters of the Arctic Ocean.
AB  - Water sampling during the 1993 IV Russian-US Joint Expedition to the Bering and
      Chukchi Seas (BERPAC) indicates that Pacific Ocean burdens of the long-lived
      radionuclide 129I are relatively low in the Pacific-influenced Arctic,
      particularly compared to high latitude waters influenced by the North Atlantic.
      These low concentrations occur despite the presence of potential submerged
      anthropogenic sources in the East Sea (Sea of Japan), and in the northwest
      Pacific Ocean, east of the Kamchatka Peninsula. The concentration of 129I
      entering the Arctic Ocean through Bering Strait, approximately 0.7 x 10(8) atoms
      kg(-1), is only slightly higher than observed in deep Pacific waters. Similar
      concentrations (0.44-0.76 x 10(8) atoms kg(-1)) measured in Long Strait indicate
      no significant transfer of 129I eastward into the Chukchi Sea in the Siberian
      Coastal Current from the Siberian marginal seas to the west. However, the
      concentrations reported here are more than an order of magnitude higher than the
      Bering Strait input concentration estimated (1.0 x 10(6) atoms kg(-1)) from bomb
      fallout mass balances, which supports other existing evidence for a significant
      atmospheric deposition term for this radionuclide in surface ocean waters. Near
      bottom water samples collected in productive waters of the Bering and Chukchi
      Seas also suggest that sediment regeneration may locally elevate 129I
      concentrations, and impact its utility as a water mass tracer. As part of this
      study, two deep 129I profiles were also measured in the East Sea in 1993-1994.
      The near-surface concentration of 129I ranged from 0.12 to 0.31 x 10(8) atoms kg(
      1). The 129I concentration showed a steady decrease with depth, although because
      of active deep water ventilation, the entire 3000 m water column exceeded natural
      concentrations of the radionuclide. Atom ratios of 129I/137Cs in the East Sea
      also suggest an excess of 129I above bomb fallout estimates, also possibly
      resulting from atmospheric deposition ultimately originating from nuclear
      facilities.

PMID- 11827123
TI  - Polycyclic aromatic hydrocarbon (PAHs) and hopanes in stranded tar-balls on the
      coasts of Peninsular Malaysia: applications of biomarkers for identifying sources
      of oil pollution.
AB  - Malaysian coasts are subjected to various threats of petroleum pollution
      including routine and accidental oil spill from tankers, spillage of crude oils
      from inland and off-shore oil fields, and run-off from land-based human
      activities. Due to its strategic location, the Straits of Malacca serves as a
      major shipping lane. This paper expands the utility of biomarker compounds,
      hopanes, in identifying the source of tar-balls stranded on Malaysian coasts. 20
      tar-ball samples collected from the east and west coast were analyzed for hopanes
      and polycyclic aromatic hydrocarbons (PAHs). Four of the 13 tar-ball samples
      collected from the west coast of Peninsular Malaysia were identified as the
      Middle East crude oil (MECO) based on their biomarker signatures, suggesting
      tanker-derived sources significantly contributing the petroleum pollution in the
      Straits of Malacca. The tar-balls found on the east coast seem to originate from
      the offshore oil platforms in the South China Sea. The presence of South East
      Asian crude oil (SEACO) tar-balls on the west coast carry several plausible
      explanations. Some of the tar-balls could have been transported via sea currents
      from the east coast. The tankers carrying SEACO to other countries could have
      accidentally spilt the oil as well. Furthermore, discharge of tank washings and
      ballast water from the tankers were suggested based on the abundance in higher
      molecular weight n-alkanes and the absence of unresolved complex mixture (UCM) in
      the tar-ball samples. The other possibilities are that the tar-balls may have
      been originated from the Sumatran oil fields and spillage of domestic oil from
      oil refineries in Port Dickson and Malacca. The results of PAHs analysis suggest
      that all the tar-ball samples have undergone various extent of weathering through
      evaporation, dissolution and photooxidation.

PMID- 11827124
TI  - Effects of nutrients on crude oil biodegradation in the upper intertidal zone.
AB  - To enhance biodegradation, nutrients in the form of slow-release fertilizer (SRF)
      were applied to oil-contaminated microcosms (3%, v/v) which simulated intertidal
      environmental systems. Although nutrient concentrations in the interstitial water
      were not proportional to those in amended SRF, microbial activity, growth of oil
      degrading microorganisms, and oil-degradation rate were closely related to the
      concentration of nutrients in the interstitial water. Adding nutrients at higher
      dose (microcosm I, 144.4 mg C/kg sand/day, versus microcosm II, 8.5 mg C/kg
      sand/day) had a positive effect on oil degradation rate, which was especially
      obvious during the early phase of treatment. Use of pristane, phytane, and nor
      hopane as biomarkers enabled the detection of significant treatment differences
      in hydrocarbon biodegradation, which were not reliable enough when the data were
      normalized to sand mass.

PMID- 11827125
TI  - Lysosomal membrane stability and metallothioneins in digestive gland of Mussels
      (Mytilus galloprovincialis Lam.) as biomarkers in a field study.
AB  - The lysosomal membrane destabilization and the metallothionein content in the
      digestive gland cells of mussels (Mytilus galloprovincialis Lam.), collected
      along the east coast of the North Adriatic (Istrian and Kvarnerine coast,
      Croatia), were examined over a period of four years (1996-1999). The lysosomal
      membrane stability, as a biomarker of general stress, showed that the membrane
      labilization period in mussels from polluted, urban- and industrial-related areas
      was significantly decreased (p < 0.05) when compared to mussels from control,
      clean seawater sites. In the harbour of Rijeka, the most contaminated site, the
      lysosomal membrane stability was reduced by more than 70% compared to the
      control. This method also proved to be a useful biomarker for detection of
      additional stress caused by short-term hypoxia that occurred once during this
      study inside the polluted and periodically quite eutrophic Pula Harbour. The
      concentration of metallothioneins in the mussel digestive gland, as a specific
      biomarker of exposure to heavy metals, did not reveal significant differences (p
      < 0.05) between sites covered by this study.

PMID- 11827126
TI  - Influence of algal farming on fish assemblages.
AB  - We examined the influence of algal farming on fish assemblages in two shallow
      coastal lagoons in Zanzibar, Tanzania. Fish assemblages were visually
      investigated using a belt transect method and the line-intercept technique was
      used to examine the substrate composition. 101 species of fish belonging to 31
      families were recorded. Algal farming affected the associated fish fauna in terms
      of abundance, species richness, trophic identity and fish community composition.
      However, the impact differed between the lagoons. Algal farms in one lagoon
      hosted a more abundant and diversified fish fauna than controls, whereas farms in
      the other lagoon exhibited lower fish densities and similar species diversity
      compared to controls. The discrepancies between lagoons may be an effect of
      differences in farming intensity and character of the substratum.

PMID- 11827127
TI  - Variations in cardiac activity following acute exposure to copper in three co
      occurring but differently zoned Mediterranean limpets.
AB  - The cardiac activity of three limpets (Patella rustica, P. caerulea and P.
      aspera), having a different vertical zonation on the Mediterranean rocky shores,
      was monitored using a non-invasive technique, during 6 h exposure to copper
      solutions (0.1 and 0.5 ppm), and after return to copper-free conditions. At 0.1
      ppm no significant variation of heart rate was observed in the three species with
      respect to control conditions, while after 3 h at 0.5 ppm a consistent
      bradycardia was evident in P. caerulea and P. aspera, but not in P. rustica.
      After 6 h at 0.5 ppm most of the specimens of the three species were acardic but
      still reactive to mechanical stimulation. Tests on the resumption of cardiac
      activity after 6 h exposure to 0.5 ppm showed that even after a prolonged
      cessation of cardiac activity, limpets quickly resumed heartbeating once returned
      to clean seawater. However, recovery of heart-beating was faster in the mid- and
      high-shore species (P. caerulea and P. rustica, respectively) than in the lower
      shore P. aspera. Moreover, the cardiac pattern upon recovery was definitely
      bradycardic in P. aspera, while the other two species showed a significant
      overshooting in heartbeating rate. Measurement of body burdens of copper showed
      that P. rustica and P. caerulea were faster in removing the excess of copper than
      the lower-shore P. aspera. In conclusion, this study showed that taxonomically
      close and syntopic species having a different zonal distribution exhibit
      different cardiac responses to water-borne copper and stresses the importance of
      comparative studies on physiological responses of organisms to metal pollution.

PMID- 11827128
TI  - The contribution of ecdysis to the fate of copper, zinc and cadmium in grass
      shrimp, Palaemonetes pugio Holthius.
AB  - Depuration through ecdysis by grass shrimp, Palaemonetes pugio, was examined by
      exposure to a sublethal mixture of copper, zinc and cadmium for 72 h, followed by
      placement in uncontaminated water to molt. Percent eliminated with the exuviae
      varied for each metal; of the total intermolt body burden, 11% Cu, 18% Zn and 26%
      Cd was associated with the exuviae. Cu concentrations of intermolt exoskeletons
      were significantly higher than of the exuviae of post-ecdysis shrimp suggesting
      that Cu contained in the exoskeleton was reabsorbed before molting. Exuvial Cd
      concentration was not significantly different than the concentration of the
      intermolt exoskeleton, suggesting that most Cd in the exoskeleton was depurated
      with the exuviae. Although Zn whole-body burdens were lower after a molt, Zn
      losses were most likely due to excretion because exuvial concentrations were
      significantly lower than in the intermolt exoskeleton. Cu, Cd and Zn
      concentrations in exuviae shed in metal-enriched water were significantly higher
      due to adsorption than exuviae produced in uncontaminated water.

PMID- 11827129
TI  - Mercury in fish from Patos and Mirim Lagoons, Southern Brazil.

PMID- 11827130
TI  - Accumulation of organic matter, heavy metals and organic compounds in surface
      sediments along the Nervion Estuary (northern Spain).

PMID- 11827131
TI  - The radionuclide content of seaweeds and seagrasses around the coast of Oman and
      the United Arab Emirates.

PMID- 11827132
TI  - Mapping the pollution gradient of the Saronikos Gulf benthos prior to the
      operation of the Athens sewage treatment plant, Greece.

PMID- 11827133
TI  - Relationship between comfort and back posture and mobility in sitting-posture.
AB  - The objective of this work is to analyze the causes of lumbar discomfort while
      sitting on a chair, by analyzing the relationship of lumbar curvature, pelvic
      inclination and their mobilities with discomfort. An experiment has been
      performed with healthy subjects, in which comfort, postural and mobility
      parameters have been measured. Their relationship has been analyzed with
      multivariate analysis. Factorial analysis has been used to represent all the
      correlated variables measured. Logistic regression and discriminant analyses have
      been used to classify discomfort/absence of discomfort. The results show that
      great changes of posture are a good indicator of discomfort, and that lordotic
      postures with forward leaned pelvis and low mobility are the principal causes of
      the increase of discomfort.

PMID- 11827134
TI  - Experimental study on fist-ellipse for Chinese auto drivers.
AB  - Sub-workspaces and the fist-ellipse of auto drivers are new concepts in the
      fields of ergonomics and automotive engineering. The paper introduces
      measurement, generation, application and location of the 95th percentile fist
      ellipse (i.e., 95th sub-workspace for gearshift) for Chinese car drivers. It is a
      rigorous scientific approach to locate gearshift handles in conventional motor
      vehicles or locate a central control handle sidestick in a recent non-steering
      wheel conceptual car, expanding the concepts of the design tool contours of SAE.

PMID- 11827135
TI  - The effects of communication modes on performance and discourse organization with
      an adaptive interface.
AB  - This paper reports a study of different communication patterns on performance
      with a simulated adaptive interface that created the impression of a talking and
      listening computer which would help participants solve problems with a computer.
      There were four levels of communication modes which differed in the restrictions
      placed on human-computer communication. Dependent measures included tasks
      completed per minute as well as participants' utterances, which were assessed for
      verbosity, disfluencies, and indices of common ground. The largest performance
      differences were found between the groups that could communicate freely and those
      where communication was restricted or denied. As restriction increased,
      performance decreased. Further, as restriction increased, the computer assumed
      greater control and verbosity decreased. Performance on the simple tasks declined
      as communication restriction increased, but no differences were observed for
      complex tasks. The results are discussed with respect to differences between
      human-human and human-computer communication as well as research on adaptive
      environments.

PMID- 11827136
TI  - Focus groups to support the industrial/product designer: a review based on
      current literature and designers' feedback.
AB  - Focus groups are widely used within human factors, social sciences and market
      research. Whilst user-research methods may be familiar to other disciplines,
      conventional design training has not, until recently, incorporated such
      activities. With the increased awareness for the necessity to elicit user needs
      beyond the functional, design research is becoming more established. However,
      there is a significant gap in training material for design research. This paper
      will review the scope of application of focus group techniques, with particular
      emphasis on the suitability of focus groups for use by industrial/product
      designers, based on the current literature and designer feedback from two case
      studies.

PMID- 11827137
TI  - A hand-ergonomics training kit: development and evaluation of a package to
      support improved awareness and critical thinking.
AB  - A need for a hand-ergonomics training kit has been identified to increase
      critical thinking concerning choice of hand tools. This study deals with the
      design, use and evaluation of a hand-ergonomics training kit for use in
      ergonomics training programmes. The effects on awareness of hand ergonomics among
      training course participants have been evaluated by means of a questionnaire and
      interviews at a car production plant in Sweden. The evaluation was carried out
      about one and a half years after training with the hand-ergonomics training kit.
      The training kit consists of a guide to practical exercises, equipment for
      measuring hand size and strength, examples of hand tools for use in practical
      exercises, equipment for testing and evaluating the hand tools and checklists and
      judgement forms for qualitative evaluation. In addition, the kit contains
      relevant scientifically based reference reports on hand ergonomics. The
      evaluation showed that the practical exercises with the hand-ergonomic training
      kit had, to a remarkable extent, increased individuals' awareness of
      anthropometric differences and of the importance of ergonomically well-designed
      hand tools. After the practical exercises with the training kit, communication
      within the plant when choosing hand tools seems to be based on objective criteria
      to a higher degree, however, the results indicate that this communication could
      be further improved.

PMID- 11827138
TI  - A method for analytically generating three-dimensional isocomfort workspace based
      on perceived discomfort.
AB  - The purpose of this study was to develop a new method for analytically generating
      three-dimensional isocomfort workspace for the upper extremities using the robot
      kinematics. Subjective perceived discomfort scores in varying postures for
      manipulating four types of controls were used. Fifteen healthy male subjects
      participated in the experiment. The subjects were asked to hold the given
      postures manipulating controls for 60 s in the seated position, and to rate their
      perceived discomfort during the following rest of 60 s using the magnitude
      estimation. Postures of the upper extremities set by shoulder and elbow motions,
      types of controls, and left right hand were selected as experimental variables,
      in which the L32 orthogonal array was adopted. The results showed that shoulder
      flexion and adduction-abduction, elbow flexion, and types of controls
      significantly affected perceived discomfort for postures operating controls, but
      hand used for operating controls did not. Depending upon the types of controls,
      four regression models predicting perceived discomfort were presented. Using the
      models, a sweeping algorithm to generate three-dimensional isocomfort workspace
      was developed, in which the robot kinematics was employed to describe the
      translational relationships between the upper arm and the lower arm/hand. It is
      expected that the isocomfort workspace can be used as a valuable design guideline
      when ergonomically designing three-dimensional workplaces.

PMID- 11827139
TI  - Physical workload on neck and upper limb using two CAD applications.
AB  - The aim was to evaluate (1) the physical workload on neck and upper limb in
      computer-aided design (CAD) work; (2) the impact of two applications
      (PROFESSIONAL-CADAM and PRO/Engineering) and (3) two input devices (computer
      mouse and keyboard), as well as (4) sitting and standing work positions. Fifteen
      CAD operators were interviewed and examined physically. For nine subjects, the
      physical workload was measured: electromyography (EMG) of trapezius and forearm
      extensor muscles, inclinometry of the head, the upper back and upper arms, as
      well as wrist goniometry. The muscular load was low in CAD work, but the inter
      individual variation was considerable. Neither the positions were extreme, nor
      the movements. The applications, per se, did not have a large impact on the
      workload, but because of the need for different input devices the effect was
      strong. Using a keyboard meant higher angular velocities than using a mouse.
      Hence, when choosing a new software, which requires mainly a mouse as input
      device, this has to be balanced against the risk of disorders.

PMID- 11827140
TI  - A comparison between analysis time and inter-analyst reliability using spectral
      analysis of kinematic data and posture classification.
AB  - This study compares the time needed to analyze data and the inter-analyst
      variability using observational posture classification vs. spectral analysis of
      upper limb kinematic measurements made using an electrogoniometer for selected
      industrial jobs. Eight trained analysts studied four jobs using both methods. An
      incomplete fixed block experimental design was used, whereby each analyst used
      one method for each job. The four jobs included (1) punch press operation, (2)
      packaging, (3) parts hanging, and (4) construction vehicle operation. The posture
      classification analysis method involved visually classifying tipper extremity
      joint angles into specific zones relative to the range of motion for every one
      third second (10 frames) of videotape. Spectral analysis required the analysts to
      identify cycle break points. The electrogoniometer signals were synchronized with
      each cycle, and power spectra for each joint were computed. The average
      difference in RMS joint deviation among analysts was 0.9 (SD = 0.61 degrees) for
      spectral analysis and 7.1 (SD = 2.53 degrees) for posture classification. The
      average difference in mean joint angle was 0.8 (SD = 0.59 degrees) for spectral
      analysis and 11.4 (SD = 1.58 degrees) for posture classification. Repetition
      frequency differed an average of 0.05 Hz (SD = 0.054 Hz) for spectral analysis
      and 0.07 Hz (SD = 0.058 Hz) for posture classification. Posture classification
      took a factor of 6.3 more time than cycle break point assignment for spectral
      analysis. Even considering the additional time needed for sensor attachment for
      direct measurement, posture classification took an average factor of 1.29 more
      time than spectral analysis using electrogoniometer data.

PMID- 11827141
TI  - The effects of probe length on Fitts' law.
AB  - Experiments were aimed at determining the effect of a human using an extended
      probe when making movements that required accuracy at the completion of the
      movement. Ten subjects performed 64 conditions of varying amplitude of movement,
      final accuracy and probe length. Movement time increased with probe lengths from
      100 to 400mm for all conditions of amplitude and required accuracy. The effect of
      probe length was included in a mathematical description of the data through a
      multiplicative term on Fitts' index of difficulty (ID), possibly arising from
      tremor of the hand probe system in controlling approach to the target. Probe
      length had the greatest effect at high ID, where a probe of 400 mm length
      increased movement time by about 25% over that for a 100mm probe. The model
      developed has application for accurate movements with long tools such as
      screwdrivers or crowbars, head-mounted devices for the disabled, or other tasks
      where the work interface is at the end of an extended probe.

PMID- 11827142
TI  - Slip prevention: validation of duplicates reproducing industrial floor surface
      state microgeometry.
AB  - The present study falls within the scope of work on the prevention of slips
      occurring on industrial workplace floor surfaces. Floor microgeometry is a
      determining factor in anti-slip flooring. Industrial environment-based
      quantification of floor microgeometrical properties is more restricting than
      laboratory quantification. The aim of the present study was to develop a
      duplication technique allowing reproduction of in situ floor microgeometry so as
      to be able to quantify this microgeometry in the laboratory. Duplicates were
      produced from a sample of five industrial floors. Surface microgeometry was
      characterized for both industrial floors and associated duplicates in order to
      study their microgeometrical changes following the duplicating operation. The
      purpose of this process was to reach a conclusion on the "reliability" of the
      duplication technique, on which the use of such duplicates depends. Parameters
      established from digitalized surfaces reveal differences of less than 5% between
      duplicates and original floor and this enables us to conclude that these
      duplicates offer a high degree of reliability with respect to results dispersion.

PMID- 11827143
TI  - The change in emphasis from people to person: introduction to the special issue
      on assistive technology.

PMID- 11827144
TI  - Factors influencing the decision to abandon manual wheelchairs for three
      individuals with a spinal cord injury.
AB  - PURPOSE: This study was conducted to identify factors which influence individuals
      with a spinal cord injury to abandon their first wheelchair before five years of
      use. It aims to provide prescribing therapists and manufacturers with insights
      which may assist in facilitating better outcomes for wheelchair users, thereby
      reducing abandonment rates and containing replacement costs. METHOD: A
      descriptive, qualitative design was used to gather the perceptions of three
      individuals with a spinal cord injury. RESULTS: Thematic analysis yielded five
      themes: 'Participants' experience of the first prescription'; 'The physical
      issues with the wheelchair have functional implications'; 'Gaining experience is
      so important'; 'Participants' experience of the second prescription'; and
      'Participants' suggestions'. CONCLUSIONS: Factors influencing manual wheelchair
      abandonment for these participants were consistent with findings from the
      literature concerning dissatisfaction and abandonment of assistive technology.
      For these three individuals the lack of experience in wheelchair use and
      selection, the functional limitations encountered with the design of the
      wheelchair and the manner and timing of the prescription process combined to lead
      to dissatisfaction and ultimately abandonment. Suggestions for changes to
      wheelchair prescription practices were made.

PMID- 11827145
TI  - Toward a comprehensive evaluation of the impact of electronic aids to daily
      living: evaluation of consumer satisfaction.
AB  - PURPOSE: It is generally accepted that electronic aids to daily living (EADLs)
      play an important role in the lives of many people with severe disabilities by
      providing the means to access and control devices for daily living activities.
      Despite this, little proof exists to support the contention that consumers are
      satisfied with relevant aspects of these assistive devices. The purpose of this
      study was to explore consumer satisfaction with EADLs and investigate the value
      that people with degenerative neuromuscular conditions place on these
      technologies. METHOD: Interviews were conducted with 40 EADL users and non-users
      to compare their views about these devices and their daily life experiences.
      Users were interviewed twice, six months apart, to establish the stability of
      their views and experiences with EADLs. The Functional Independence Measure (FIM
      instrument), the personal profile and Quebec User Evaluation of Satisfaction with
      assistive Technology (QUEST) were administered to determine functional levels of
      participants, gather personal data pertinent to the study of device utility and
      explore user satisfaction with EADLs. RESULTS: Results suggest that overall
      consumers were quite satisfied with their EADLs and that this was relatively
      stable over time. However, some consumers expressed concerns regarding the cost
      of these technologies and their associated services. Both users and non-users
      rated EADLs similarly in relation to relative degree of importance ascribed to
      them. CONCLUSIONS: Combining the QUEST with outcome measurement tools that
      explore other important dimensions such as the effect on quality of life and
      psychosocial impact will help service providers to justify the costs associated
      with the prescription of sophisticated, costly assistive devices such as EADLs.

PMID- 11827146
TI  - Determining the content for an interactive training programme and interpretive
      guidelines for the Assistive Technology Device Predisposition Assessment.
AB  - PURPOSE: Develop the content for interpretive guidelines and an interactive
      training programme for professionals administering the Assistive Technology
      Device Predisposition Assessment (ATD PA) consumer form, a self-report assessment
      tool for consumers to identify their perceived functional capabilities and
      limitations, satisfaction with and priorities for quality of life achievement,
      psychosocial characteristics and device preferences. METHOD: Twenty-two
      professionals (with 1-2 consumers each) completed surveys on their use of the ATD
      PA and recommendations for interpretive guidelines and an interactive training
      programme. Participants represent eight US states and the country of Italy.
      Fourteen women and eight men (professionals) participated, and 20% of the sample
      was comprised of US consumers from Hispanic or African-American ethnic groups.
      Professionals represented the following disciplines: occupational therapy (n=1);
      physical therapy (n=1); rehabilitation engineering (n=4); and vocational
      rehabilitation counselling (n=16). Additionally, an advisory committee of 14
      persons was formed, comprising consumers as well as international AT experts. The
      committee members prioritized content areas for the training programme and
      interpretive guidelines. RESULTS/CONCLUSIONS: Responses strongly support the need
      for and the continued development of the training programme and interpretive
      guidelines. Content areas have been identified and prioritized.

PMID- 11827147
TI  - Development and evaluation of the Families, Cultures and Augmentative and
      Alternative Communication (AAC) multimedia program.
AB  - PURPOSE: The Families, Cultures and AAC Project was designed to provide
      professionals and families with accurate, culturally sensitive information about
      augmentative communication technologies and decision-making strategies through an
      innovative, user-friendly format. METHODS: The project resulted in the
      development of the first interactive bilingual CD-ROM designed to be used by
      professionals at the pre- or in-service level, and family members from diverse
      cultures to develop AAC decision-making competencies. RESULTS: The Interactive
      Health Communication (IHC) model provided an effective structure for
      conceptualizing, developing and evaluating the program. The program also
      incorporated universal access design concepts. The program was evaluated in the
      following 10 categories: usability, visual appearance, consistency, error
      tolerance, navigation, feedback, user control, redundant formats, content
      accuracy, and engaging styles. CONCLUSION: Reviewers of the program indicated
      that it was well designed and would be useful for the intended purpose.

PMID- 11827148
TI  - Assistive technology education: an online model for rehabilitation professionals.
AB  - PURPOSE: A model for delivering Assistive Technology (AT) education is described
      in the context of an online masters degree in rehabilitation counselling,
      demonstrating the integration of content and process in an interactive format.
      METHOD: Data collected from course activities and assignments were examined to
      identify ways in which 120 students from 18 US states responded to and interacted
      with the information and how they applied the course content to their jobs as
      rehabilitation professionals. A qualitative research design was used to identify
      themes to add to the understanding of issues associated with learning about AT in
      an online format. RESULTS: Critical components of the course identified from the
      data analysis included: increased awareness, skills, confidence, and immediate
      application to own job responsibilities; interaction with instructors and peers;
      access to resources and expertise; value-based practices; and participation on
      interdisciplinary teams. These themes were consistent across all six groups of
      students enrolled in the participating three rehabilitation regions. CONCLUSIONS:
      Online education can be an effective medium for teaching practicing
      rehabilitation professionals how to provide person-centred AT services to people
      with disabilities. The content must drive the technology; the process must be
      student-driven; and the interaction must address individual learning styles and
      promote lifelong learning.

PMID- 11827149
TI  - Being informed, demanding and responsible consumers of assistive technology: an
      educational issue.
AB  - PURPOSE: Awareness and knowledge of Assistive Technology (AT) are key factors in
      supporting empowerment of people with disabilities. They also greatly contribute
      to the success of AT solutions. Based on the findings of the EUSTAT study--an
      international project within the Telematics Application Programme of the European
      Commission--this paper offers a synthesis of the guidelines developed for those
      who organize educational activities on AT addressed towards end-users. RESULTS:
      The educational process is looked at within an empowerment perspective rather
      that as a mere transmission of notions. The effectiveness of education should be
      evaluated in relation to the increased ability of end users to make use of AT
      knowledge for improving their quality of life, and becoming informed, demanding
      and responsible consumers of AT products and services. CONCLUSION: To such end a
      number of critical factors are identified, and ways to address them are
      discussed. Finally, a case study is reported as an example of an effective AT
      educational curriculum for end-users.

PMID- 11827150
TI  - Delivering an AT service: a client-focused, social and participatory service
      delivery model in assistive technology in Ireland.
AB  - PURPOSE: This article outlines the development of an Assistive Technology (AT)
      service delivery model and suggests that a client-focused social and
      participatory service delivery model in AT can achieve the best results for
      people with disabilities and their carers. METHOD: It draws on case studies,
      which are part of the final evaluation report of the Aphrodite (European Horizon
      funded project 1998-2000) project to illustrate the success of a client-focused
      service. The aim of the project was to provide people with disabilities access to
      a local technical resource in the form of Technology Liaison Officers (TLOs).
      CONCLUSION: TLO's are people with physical disabilities, who have been trained in
      AT and who have achieved a certificate in AT, to act as a liaison between users
      and potential users of AT and the Central Remedial Clinic's (CRC) Client
      Technical Services (CTS) Department.

PMID- 11827151
TI  - Reliability, validity, and applicability of the Quebec User Evaluation of
      Satisfaction with assistive Technology (QUEST 2.0) for adults with multiple
      sclerosis.
AB  - PURPOSE: To investigate the measurement properties of the Quebec User Evaluation
      of Satisfaction with assistive Technology (QUEST 2.0) with respect to test-retest
      stability, alternate form reliability, construct validity and applicability.
      METHOD: Data on satisfaction and quality of life impacts of mobility devices were
      obtained from 81 community-based adults with Multiple Sclerosis, using the QUEST
      2.0 and the Psychosocial Impact of Assistive Devices Scale (PIADS). Subjects were
      assigned to four groups and a second QUEST 2.0 was administered one week later.
      Groups differed with respect to the format and the order in which alternate forms
      were presented. Measures of association were calculated between QUEST 2.0 and
      PIADS (n = 81) and between QUEST 2.0 alternate forms (n = 48). Respondents'
      reactions were considered. RESULTS: The device subscale, services subscale, and
      total QUEST 2.0 scores achieved good test-retest stability (ICC 0.82, 0.82,
      0.91). Alternate-form equivalence (ICC 0.89, 0.76, 0.91) was lower for services.
      The positive correlations between QUEST 2.0 and the three PIADS dimensions were
      fair to moderate for device and total QUEST 2.0 (r(p) 0.34 to 0.45) and fair with
      services (r(p) 0.27 to 0.30). The tool was positively received, with some
      restrictions for the services subscale. CONCLUSIONS: These findings on the
      psychometric properties of the QUEST 2.0 reinforce the relevance of the device
      subscale as an important outcome measure for assistive technology MS users.
      Further assessment of the services subscale is needed.

PMID- 11827152
TI  - Development of a scale to measure the psychosocial impact of assistive devices:
      lessons learned and the road ahead.
AB  - PURPOSE: In this paper the history of the development and validation of the PIADS
      is reviewed. Assistive devices (ADs) are extremely prevalent forms of health care
      intervention for persons who have a disability. There is a consensus that the AD
      field needs a reliable and valid measure of how users perceive the impact of ADs
      on their quality of life (QoL) and sense of well-being. The Psychosocial Impact
      of Assistive Devices Scale (PIADS) is a 26 item self-rating scale designed to
      fill this measurement gap. The challenges that we encountered are described in
      attempting to adequately conceptualize QOL impact, and operationalize it in a
      measure suitable for use with virtually all forms of AD. Current efforts to
      extend the validation of the PIADS are summarized. CONCLUSIONS: The study
      concludes by suggesting directions for future research and development of the
      scale. They include a richer examination of its conceptual relationships to other
      health care and rehabilitation outcome measures, and further investigation of its
      clinical utility. The PIADS is a reliable and valid tool that appears to have
      very significant power to predict AD abandonment and retention. It can and should
      be used both deductively and inductively to build, discover and test theory about
      the psychosocial impact of assistive technology.

PMID- 11827153
TI  - Development and consumer validation of the Functional Evaluation in a Wheelchair
      (FEW) instrument.
AB  - PURPOSE: The purpose of the study is to develop an outcome measurement tool to
      investigate functional performance of consumers using seating and wheelchair
      systems as their primary seating and mobility device. The instrument is
      undergoing systematic development in three phases. The results of Phase 1 will be
      reported. METHOD: Manual and power wheelchair users were interviewed using a
      modified version of a client-centred outcome measure. An item bank was derived
      based on the interview data. Subjects were then asked to validate item categories
      of the new instrument, and finally to self-administer the first version of the
      instrument. RESULTS: Subjects reported 154 self-care, productivity, and leisure
      occupational performance issues related to their current seating-mobility system.
      Based on their input, 10 categories (i.e. transfers, reach, accessing task
      surfaces, transportation-portability, human-machine interface, architectural
      barriers, transportation-accessibility, transportation-securement, natural
      barriers and accessories) were validated for inclusion in the new outcome
      measure, Functional Evaluation in a Wheelchair (FEW). CONCLUSION: The items on
      the FEW focus on the interaction between the consumer, the technology, and the
      milieu. Consumers viewed the overall importance of FEW categories for seating
      mobility system users differently than when they self-administered the FEW.

PMID- 11827154
TI  - The development of an instrument to match individuals with disabilities and
      service animals.
AB  - PURPOSE: There has been an increase in the use of service animals assisting
      persons with disabilities in the past decade. However many of the service dog
      agencies do not utilize an assessment that is designed to match the person to the
      animal in the rehabilitation and psycho-social domains. The purpose of this study
      was to develop the Service Animal Adaptive Intervention Assessment (SAAIA) and to
      measure the content validity, inter-rater reliability and clinical utility of the
      assessment. METHOD: Two subject groups were used. Subject group one had 43
      subjects who measured the content validity and clinical utility of the SAAIA
      Survey. Subject group two had 12 subjects who measured the inter-rater
      reliability by completing the SAAIA using information obtained through a video
      taped client case scenario. RESULTS: Content validity results indicated a good to
      high percentage of agreement and a fair percentage of agreement for clinical
      utility. Inter-rater reliability results indicate good to high agreement on six
      of the eight variables of the SAAIA. However, the Kappa score indicates low inter
      rater reliability. CONCLUSION: Results indicate the SAAIA has good content
      validity and inter-rater reliability and fair clinical utility based on percent
      agreement. However, further research is needed on the reliability of the SAAIA.

PMID- 11827155
TI  - The shaping of individual meanings assigned to assistive technology: a review of
      personal factors.
AB  - PURPOSE: This review article examines the development of individualized meanings
      assigned to assistive technology and how these personal meanings influence the
      integration of assistive technology into daily activities. METHODS: A review of
      the published literature regarding assistive technology use and abandonment was
      conducted by performing two independent searches using 26 search terms and three
      databases. Publications were reviewed for whether they addressed device use,
      device abandonment, coping, adjustment, adaptation, values, outcomes and/or
      cultural issues; 81 publications met these criteria. RESULTS: The evidence
      suggests that psychosocial and cultural issues influence the shaping of
      individualized meanings assigned to assistive technology. Theoretical arguments
      suggest that the process of adapting to disability is another influential factor.
      CONCLUSIONS: The synthesis of evidence and theories suggests that successful
      integration of assistive technology into daily lives requires potential device
      users to explore: (1) the meanings they assign to devices; (2) their expectations
      of assistive technology; (3) the anticipated social costs; and (4) ways to
      understand that disability is one, but not the defining, feature of one's
      identity.

PMID- 11827156
TI  - Evaluating home environments of persons with dementia: interrater reliability and
      validity of the Home Environmental Assessment Protocol (HEAP).
AB  - PURPOSE: This article reports on an interrater reliability and preliminary
      validity study of an investigator-developed tool, the Home Environmental
      Assessment Protocol (HEAP) for use in homes of persons with dementia. METHOD: The
      HEAP consists of 192 items that are summed into separate indices representing the
      number of hazards, adaptations, and level of clutter and comfort in eight areas
      of the home. Interrater reliability was examined among four raters, two
      environmental experts and two non-experts, who observed 22 dementia households.
      RESULTS: The Kappa statistic was used to evaluate agreement level for each
      measured item and found that agreement ranged from slight to almost perfect.
      Intraclass correlations (ICCs), were used to evaluate agreement level for
      indices. The hazard index in each room ranged from fair (0.36) to moderate (0.66)
      for all raters. For the adaptation, clutter and comfort indices in each room,
      ICCs ranged from 0.51 to 0.90 for all raters. Agreement level between expert and
      non-expert raters differed minimally for all indices. Adaptations to dining rooms
      (r= -0.080, p = 0.001), kitchens (r = -0.52, p = 0.02) and bedrooms (r = -0.76, p
      = 0.001) were associated with patient deficits such that more adaptations were
      made in homes of dependent persons. Low Mini-Mental Status Examination scores
      were associated with fewer hazards, more adaptations, and less clutter.
      CONCLUSION: Findings show that both experts and non-expert raters use the HEAP
      consistently. Also, measured attributes are related to cognitive and functional
      status in the expected direction.

PMID- 11827157
TI  - An Italian research project to study the play of children with motor
      disabilities: the first year of activity.
AB  - PURPOSE: The paper presents the main outline of a new research project carried
      out by the SIVA research team concerning the development of methodologies to
      select and use assistive technology to allow children with motor disabilities to
      play with toys. CONCLUSION: Giving them the same opportunities to play as their
      peers without disabilities can best enhance their cognitive and social
      development. A review of the literature in the field is also included.

PMID- 11827158
TI  - Adoption of assistive technology for computer access among college students with
      disabilities.
AB  - PURPOSE: Fourteen college students with disabilities identified factors that
      influenced them to adopt or reject Assistive Technology (AT) for the personal
      computer in order to assess the effectiveness of a college course on adapted
      computer use. METHOD: Forty-eight items were developed for a Q sort to represent
      both positive and negative statements in each of the three areas of Scherer's'
      model (milieu, person and technology). The model was modified to include specific
      statements about the training experience. A series of three interviews were
      administered to the students during the year following completion of the class.
      RESULTS: Factor analysis of the Q sorts indicated that the participants had a
      unanimously positive experience. Three factors ('a positive experience', 'I'm OK,
      you're not OK', and 'support') emerged from the Q sort analysis. The training
      programme, the technology provided, and the characteristics of the individuals in
      the class all seemed to contribute to the success of the experience. Seventy-five
      percent of the students who took the class adopted at least some of the AT a year
      later. CONCLUSIONS: This study supports the need for specific training programmes
      and course work for college students with disabilities who are interested in
      improving computer access skills.

PMID- 11827159
TI  - The impact of assistive technology and environmental interventions on function
      and living situation status with people who are ageing with developmental
      disabilities.
AB  - PURPOSE: A longitudinal study of 109 people with developmental disabilities, age
      35 and older, was done to study the additive impact of mid to later life
      assistive technology and environmental interventions (AT-EI) on function and
      living situation status. All subjects were trying to transition out of
      institutional settings to community settings. METHOD: Functional status were
      measured at two times (Time I baseline and Time 2 an average of three years post
      intervention) on 32 functional activities under two conditions: without AT
      (person only) and with AT (environment adjusted). Rasch analysis was performed to
      convert ordinal functional scores to equal interval measures, with 95% confidence
      intervals computed to compare differences in function, with and without AT,
      across time. RESULTS: Results indicated that over 70% of subjects had better
      function with AT versus without AT at both time points. Over time, function did
      not change when rated without AT; however, when rated with AT, 13.6% had better
      function at Time 2. Subjects living in the community at Time 2 had significantly
      higher functional scores as compared to subjects in institutions, regardless of
      AT condition. Additional quantitative and qualitative data on AT-EI use, needs,
      and barriers and supports to its integration into everyday activities are
      reported. CONCLUSIONS: Results suggest a beneficial impact of later life AT-EI
      assessment and programming for people who are ageing with developmental
      disabilities, and qualitatively point to the influence of the social and physical
      living context upon AT-EI use and relationship to community living decisions long
      term.

PMID- 11827160
TI  - Environmental reprogramming of the expression of protein kinase CK2beta subunit
      in fish.
AB  - The dramatic segregation of the nucleolar components in winter-acclimatized carp
      is the most striking cellular-phenotypical feature observed during the seasonal
      adaptation of this fish toward the circannual changes in its habitat. Our studies
      also show that the carp habitat temperature and photoperiod winter conditions
      provoke a remarkable reduction of both rRNA transcription and the processing of
      their precursors. To gain knowledge on the mechanisms involved in the regulation
      of nucleolar activity during the seasonal adaptation process, we studied the
      behavior of some genes, specifically snoRNA U3 and protein kinase CK2. Consistent
      with the reduction in the synthesis and processing of pre-rRNA observed during
      the cold season, the level of CK2beta expression decreases in winter when
      compared to that attained in summer. Similarly, in winter, liver and kidney cells
      contain lower levels of CK2beta subunit protein compared to summer. CK2 is
      associated with or modifies different factors and enzymes involved in the
      nucleolar activity; therefore, its higher or lower content could be part of the
      molecular mechanisms underlying the nucleolar seasonal changes that occur during
      the compensatory acclimatization process.

PMID- 11827161
TI  - Mutation at the CK2 phosphorylation site on Cdc28 affects kinase activity and
      cell size in Saccharomyces cerevisiae.
AB  - We have recently reported that protein kinase CK2 phosphorylates both in vivo and
      in vitro residue serine-46 of the cell cycle regulating protein Cdc28 of budding
      yeast Saccharomyces cerevisiae, confirming a previous observation that the same
      site is phosphorylated in Cdc2/Cdk1, the human homolog of Cdc28. In addition, S.
      cerevisiae in which serine-46 of Cdc28 has been mutated to alanine show a
      decrease of 33% in both cell volume and protein content, providing the genetic
      evidence that CK2 is involved in the regulation of budding yeast cell division
      cycle, and suggesting that this regulation may be brought about in G1 phase of
      the mammalian cell cycle. Here, we extended this observation reporting that the
      mutation of serine-46 of Cdc28 to glutamic acid doubles, at least in vitro, the
      H1-kinase activity of the Cdc28/cyclin A complex. Since this mutation has only
      little effects on the cell size of the cells, we hypothesize multiple roles of
      yeast CK2 in regulating the G1 transition in budding yeast.

PMID- 11827163
TI  - Cloning and characterization of the cDNA coding for the catalytic alpha subunit
      of CK2 from tobacco.
AB  - We have previously reported the participation of the protein kinase CK2 in the
      mechanism by which salicylic acid activates transcription of genes, such as those
      coding for glutathion S-transferases, in tobacco. With the purpose of further
      studying the participation of CK2 in this signal transduction pathway, we
      isolated and sequenced the cDNA from the NtCK2A gene, coding for the catalytic
      alpha subunit of CK2 from tobacco. The NtCK2A cDNA was isolated by screening of a
      tobacco cDNA library with a heterologous probe from Arabidopsis thaliana,
      followed by 3' RACE to obtain the 3' region. Sequence analysis of the NtCK2A cDNA
      showed a high level of identity between this CK2alpha protein sequence and the
      corresponding sequences of other plant species such as Arabidopsis and maize (92
      95% identity), or those of animal species such as human and Xenopus laevis (75%
      identity). The expression of the NtCK2A gene in different tissues from tobacco
      plants was analyzed by Northern blot. High levels of expression of this gene were
      observed in proliferating tissues such as shoot and root apical meristems. A
      recombinant CK2alpha protein was obtained after expression of the NtCK2A cDNA in
      Escherichia coli. The ability of this recombinant CK2alpha subunit to
      phosphorylate casein was inhibited by heparin and stimulated by the CK2beta
      subunit from Xenopus laevis.

PMID- 11827162
TI  - Distinctive features of plant protein kinase CK2.
AB  - In plants, protein kinase CK2 is involved in different processes that control
      many aspects of metabolism and development. In mammals and yeast the enzyme is a
      heterotetramer composed of two types of subunits. During years the subunit
      composition of the maize protein kinase CK2 enzyme has been a source of
      controversy. We have recently characterized the maize holoenzyme subunits. Our
      results show that multiple catalytic and regulatory subunits are expressed in
      maize and are able to specifically interact with other alpha and beta subunits
      suggesting a high level of heterogeneity in the typical heterotetrameric
      structure. Here, we summarize data available on plant CK2 enzymes, in order to
      clarify the distinctive features and functions of plant protein kinase CK2.

PMID- 11827164
TI  - Generation of mutants of CK2alpha which are dependent on the beta-subunit for
      catalytic activity.
AB  - To shed light on the structural features underlying high constitutive activity of
      protein kinase CK2 a number of mutants of the human CK2alpha-subunit altered in
      the interactions between the N-terminal segment and the activation loop have been
      generated and shown to be defective in catalytic activity. In particular the
      truncated mutant delta2-12 displays under standard conditions an almost complete
      loss of catalytic activity accounted for by a dramatic rise in its Km forATP
      (from 10 to 206 microM) and a reduced Kcat. Such a drop in efficiency is
      paralleled by conformational disorganization, as judged from Superdex 75 gel
      filtration profile. Both catalytic properties and gel filtration behaviour
      similar to those of wild type CK2alpha were restored upon association with the
      regulatory beta-subunit, suggesting that constitutive activity is conferred to
      CK2alpha and to CK2 holoenzyme through different molecular mechanisms. In the
      holoenzyme an assumable release of tension at the backbone of Ala-193 (as seems
      to be indicated by a comparison of the crystal structures of maize CK2alpha alone
      vs. a CK2alpha-beta peptide complex) may result in the ability of the activation
      loop to adopt its proper conformation independently of interactions with the N
      terminal segment.

PMID- 11827165
TI  - Regulation of the human papillomavirus oncoproteins by differential
      phosphorylation.
AB  - Human papillomaviruses (HPVs) are intimately associated with the development of
      cervical cancer. The virus encodes two oncoproteins, E6 and E7, that are
      primarily responsible for inducing malignant transformation. The last few years
      have seen significant progress in elucidating the mechanisms by which these two
      viral proteins bring about cell transformation. Both proteins interact with a
      large number of cellular targets, many of which are involved in regulating
      diverse functions such as cell cycle regulation, transcription, differentiation
      and apoptosis. However both E6 and E7 are normally present at low levels within
      the virally infected cell, and how all these interactions are achieved and
      regulated has, until recently, been unclear. We have found that both E6 and E7
      are subject to differential phosphorylation, the net results of which regulate
      their abilities to interact with some of their respective target proteins. In the
      case of E6, phosphorylation by Protein Kinase A (PKA) negatively regulates its
      ability to interact with the Discs Large (Dlg) tumour suppressor. In the case of
      E7, phosphorylation by Casein Kinase II (CKII) significantly increases its
      ability to interact with the TATA Box Binding Protein (TBP). Further, CKII
      regulation of E7 appears to vary during the cell cycle, therefore this provides a
      means of specifically targeting E7 to a given substrate at a given point within
      the cell cycle. This differential regulation of E6 and E7 by phosphorylation thus
      provides specificity to a diverse set of protein-protein interactions.

PMID- 11827166
TI  - HIV-1 Rev transactivator: a beta-subunit directed substrate and effector of
      protein kinase CK2.
AB  - The phosphorylation of HIV-1 Rev by protein kinase CK2 is strictly dependent on
      the regulatory beta subunit of the kinase and is deeply affected by
      conformational changes of the substrate outside the phosphorylation site. Here we
      show that Rev modulates a variety of CK2 properties, including
      autophosphorylation, catalytic activity toward calmodulin, and susceptibility to
      polycationic effectors, whose common denominator is the involvement of the beta
      subunit. Rev's two major CK2 sites are located at its N-terminus, immediately
      adjacent to a helix-loop-helix motif. By comparing the behaviour of full-size Rev
      with that of synthetic peptides reproducing, with suitable modifications, its N
      terminal 26 amino acids including the phosphoacceptor site (Ser 5, Ser 8) and
      amphipathic helix-1, it appears that the functional interaction of the N-terminal
      portion of Rev with the N-terminal domain of the beta subunit must rely on both
      electrostatic and hydrophobic interactions. The former mainly involve Rev's
      arginine-rich domain (residues 35-50) in helix-2, while the latter are mostly
      mediated by residues 12-24 of helix-1. These data disclose the possibility that,
      besides displaying protective, regulatory and targeting properties with respect
      to the catalytic subunit, the CK2 beta subunit also plays a role as a docking
      site for a subset of CK2 substrates.

PMID- 11827167
TI  - Protein kinase CK2: signaling and tumorigenesis in the mammary gland.
AB  - Breast cancer is a major cause of cancer death in women, and the genetic
      abnormalities leading to the common sporadic forms of the disease are still under
      active investigation. CK2 has been reported to be upregulated in human breast
      cancer, which these studies confirm; CK2 is also upregulated in rat carcinogen
      induced breast tumors. Transgenic mice overexpressing CK2alpha in the mammary
      gland develop mammary hyperplasia, dysplasia, and eventually adenocarcinomas,
      demonstrating that dysregulated expression of CK2 can contribute to
      transformation of the mammary epithelium. These mammary tumors have evidence of
      activation of the Wnt and NFkappaB pathways and upregulation of c-Myc. CK2 is
      capable of phosphorylating the key signaling molecule in the Wnt pathway, the
      transcriptional cofactor beta-catenin, and regulating its turnover. CK2 is known
      to phosphorylate IkappaB and thereby regulate basal NFkappaB levels; in the
      mammary cell lines and tumors, CK2 activity correlates with NFkappaB levels and
      inhibition of CK2 downregulates NFkappaB. Thus, CK2 may promote breast cancer
      through dysregulation of key pathways of transcriptional control in the mammary
      epithelium, and inhibition of CK2 has a potential role in the treatment of breast
      and other cancers.

PMID- 11827168
TI  - Response of cancer cells to molecular interruption of the CK2 signal.
AB  - Protein kinase CK2 is one of the key cellular signals for cell survival, growth,
      and proliferation. It is has been observed to be elevated in various cancers that
      have been examined. Various observations suggest that moderate dysregulation of
      CK2 may profoundly influence the cell response. We have examined the effects of
      interfering with the CK2 signal in various cancer cell lines by employing
      antisense oligodeoxynucleotides (ODN) against the alpha and beta subunits of CK2.
      Our results demonstrate that antisense CK2-alpha and antisense CK2-beta ODNs
      markedly influence cell viability of these cancer cells in a dose and time
      dependent manner. Antisense CK2-alpha was slightly more effective than antisense
      CK2-beta in most of the cells tested. The efficacy of the antisense ODN seemed to
      vary with the cell type; however, in all cases potent induction of apoptosis was
      observed. Significantly, the effects of the antisense ODN on the CK2 activity in
      the nuclear matrix were relatively small compared to the much stronger induction
      of apoptosis in cells. This suggests that modest downregulation of CK2 can evoke
      a much greater apoptotic response in cancer cells.

PMID- 11827169
TI  - The genomic structure of two protein kinase CK2alpha genes of Xenopus laevis and
      features of the putative promoter region.
AB  - Protein kinase CK2 is an enzyme that is ubiquitous in eukaryotes. This enzyme,
      composed of catalytic (alpha and alpha') and regulatory (beta) subunits, is
      responsible for the phosphorylation of a large number of proteins and is
      implicated in cell division. Genomic clones coding for the CK2alpha subunit of
      Xenopus laevis have been isolated. Initial restriction enzyme profiles and
      subsequent PCR analysis and DNA sequencing indicated that these genomic clones
      correspond to two different genes. The two genes are highly homologous in the
      regions of the coding sequence (only 3 amino acid differences) but differ
      considerable in their intron sequences and lengths. Gene 1 corresponds to the
      cDNA of XlCK2alpha which had been previously isolated and described. The genomic
      clone for this gene was truncated. Gene 2 contains the entire coding region for
      CK2alpha subunit as well as a fragment of 6.4 kb of the 5' upstream region. The
      exon/intron boundaries of both genes obey the GT/AG rule with the exception of
      intron V where the less common GC/AG is seen. Comparison of the size of ten
      coding exons and sites where these are interrupted by introns shows strong
      conservation with respect to the human CK2alpha gene. RT-PCR analysis of mRNAs
      from X. laevis ovary, oocytes and early embryos using a specific primer for gene
      2 demonstrated that this gene is expressed in these tissues and cells. Analysis
      of transcription start sites using 5'RACE and RNA from stage VI oocytes
      demonstrated that there are multiple start sites in the XlCK2alpha mRNA. It was
      also seen that a noncoding exon 1 is present 4 kb upstream of the translation
      start site and that alternate splicing occurs in gene 2 to give exon 1 of
      different lengths. Sequencing of the entire upstream genomic region of gene 2
      revealed that there are regions of homology to the sequence of exon 1 of the
      human CK2alpha gene. Other sequences with consensus to transcription factor
      binding sites that are seen in the promoter region of human CK2alpha are also
      found in the X. laevis CK2alpha gene 2. These sites include Ets1, E2F, CCAAT and
      GC rich regions. No canonical TATA motif is observed.

PMID- 11827171
TI  - Characterization of CK2 holoenzyme variants with regard to crystallization.
AB  - A search for strategies was conducted in order to obtain a human protein kinase
      CK2 preparation which would be suitable for crystallization, despite the fact
      that the recombinant enzyme is abundant and can be readily purified to
      homogeneity. This seemingly contradiction is based on the fact that the catalytic
      subunit moiety of the human CK2 holoenzyme is not stable neither as a free
      subunit nor in the tetrameric complex. All attempts to prevent degradation
      failed. Hence, alternative approaches were designed in order to avoid this
      degradation, which was expected to hamper any crystallization efforts severely.
      One of the approaches chosen was the production of a chimeric holoenzyme made up
      from a human regulatory subunit and a catalytic subunit from Z. mays. The plant
      catalytic subunit, in contrast to the human counterpart is very stable and does
      not undergo this kind of degradation. The second strategy to tackle the problem
      of instability was to produce the homologous recombinant human CK2 holoenzyme and
      then, instead of trying to avoid degradation, attempt to accelerate degradation
      until all catalytic subunit material was converted to the degraded form, i.e. a
      40 kDa polypeptide.

PMID- 11827170
TI  - Functional specialization of CK2 isoforms and characterization of isoform
      specific binding partners.
AB  - In mammals, protein kinase CK2 has two isozymic forms of its catalytic subunit,
      designated CK2alpha and CK2alpha'. CK2alpha and CK2alpha' exhibit extensive
      similarity within their catalytic domains but have completely unrelated C
      terminal sequences. To systematically examine the cellular functions of each CK2
      isoform in mammalian cells, we have generated human osteosarcoma U2-OS cell lines
      with the expression of active or inactive versions of each CK2 isoform under the
      control of an inducible promoter. Examination of these cell lines provides
      evidence for functional specialization of CK2 isoforms at the cellular level in
      mammals with indications that CK2alpha' is involved in the control of
      proliferation and/or cell survival. To understand the molecular basis for
      functional differences between CK2alpha and CK2alpha', we have undertaken studies
      to identify proteins that interact specifically with each isoform of CK2 and
      could contribute to the regulation of their independent functions. A novel
      pleckstrin-homology domain containing protein, designated CK2-interacting protein
      1 (i.e. CKIP-1) was isolated using the yeast two hybrid system as a protein that
      interacts with CK2alpha but not CK2alpha'. When expressed in cells as a fusion
      with green fluorescent protein, CKIP-1 localizes to the cell membrane and to the
      nucleus. In this study, we present evidence from deletion analysis of CKIP-1
      suggesting that a C-terminal region containing a putative leucine zipper has a
      role in regulating its nuclear localization. Collectively, our data supports a
      model whereby CKIP-1 is a non-enzymatic regulator of CK2alpha that regulates the
      cellular functions of CK2alpha by targeting or anchoring CK2alpha to specific
      cellular localization or by functioning as an adapter to integrate CK2alpha
      mediated signaling events with components of other signal transduction pathways.

PMID- 11827172
TI  - A surface plasmon resonance study of the interactions between the component
      subunits of protein kinase CK2 and two protein substrates, casein and calmodulin.
AB  - Surface plasmon resonance has been used to study the interaction between the
      subunits composing protein kinase CK2 (two catalytic, alpha-subunits, and two
      regulatory, beta-subunits), as well as the interaction of each subunit with two
      types of protein substrates, casein, the phosphorylation of which is activated by
      the regulatory subunit, and calmodulin, which belongs to the kind of substrates
      on which the catalytic subunit is downregulated by the regulatory subunit. The
      interaction of casein with the catalytic subunit differs from the interaction
      with the holoenzyme. Similarly to the interaction with the regulatory subunit,
      the catalytic subunit interacts with the protein substrate forming a very stable,
      irreversible complex. The reconstituted holoenzyme, however, binds casein
      reversibly, displaying a binding mode similar to that displayed by the regulatory
      subunit. The interaction of calmodulin with the catalytic subunit gives place,
      like in the case of casein, to an irreversible complex. The interactions with the
      regulatory subunit and with the holoenzyme were practically negligible, and the
      interaction with the regulatory subunit disappeared upon increasing the
      temperature value to close to 30 degrees C. The presence of polylysine induced a
      high increase in the extent of calmodulin binding to the holoenzyme. The results
      obtained suggest that CK2beta subunit and protein substrates share a common, or
      at least an overlapping, site of interaction on the catalytic subunit. The
      interaction between both subunits would prevent substrates from binding
      irreversibly to alpha subunit, and, at the same time, it would generate a new and
      milder site of interaction between the whole holoenzyme and the protein
      substrate. The main difference between casein and calmodulin would consist in the
      lower affinity display by the last for the new site generated upon the binding of
      the regulatory subunit, in the absence of polycations like polylysine.

PMID- 11827173
TI  - The activity of CK2 in the extracts of COS-7 cells transfected with wild type and
      mutant subunits of protein kinase CK2.
AB  - Protein kinase CK2 is ubiquitous in eukaryotes and is known to phosphorylate many
      protein substrates. The enzyme is normally a heterotetramer composed of catalytic
      (alpha and alpha') and regulatory (beta) subunits. The physiological regulation
      of the enzyme is still unknown but one of the factors that may play an important
      role in this regulation is the ratio of the catalytic and regulatory subunits
      present in cells. The possible existence of 'free' CK2 subunits, not forming part
      of the holoenzyme, may be relevant to the physiological function of the enzyme in
      substrate selection or in the interaction of the subunits with other partners.
      The objective of this work was to study in COS-7 cells the effects of transient
      expression of CK2 subunits and mutants of the catalytic subunit on the CK2
      phosphorylating activity of the extracts of these cells. Using pCEFL vectors that
      introduce hemagglutinin (HA) or a heptapeptide (AU5) tags in the expressed
      proteins, COS-7 cells were transfected with alpha and beta subunits of Xenopus
      CK2, with the alpha' subunit of D. rerio, and with Xl CK2alphaA156, which
      although inactive can bind tightly to CK2beta, and with Xl CK2alphaE75E76, which
      is resistant to heparin and polyanion inhibition. The efficiency of transient
      transfection was of 10-20% of treated cells. Expression of CK2alpha or
      CK2alphaE75E76 in COS-7 cells caused an increase of 5-7-fold of the CK2 activity
      in the soluble cell extracts. If these catalytic subunits were cotransfected with
      CK2beta, the activity increased further to 15-20-fold of the controls.
      Transfection of CK2beta alone also increase the activity of the extracts about 2
      fold. Transfection with the inactive CK2alphaA156 yielded extracts with CK2
      activities not significantly different from those transfected with the empty
      vectors. However, co-transfection of CK2alpha or CK2alphaE75E76 with CK2alphaA156
      caused a 60-70% decrease in the CK2 activity as compared to those of cells
      transfected with only the active CK2alpha subunits. These results can be
      interpreted as meaning that CK2alphaA156 is a dominant negative mutant that can
      compete with the other catalytic subunits for the CK2beta subunit. Addition of
      recombinant CK2beta to the assay system of extracts of cells transfected with
      catalytic subunits causes a very significant increase in their CK2 activity,
      demonstrating that CK2beta subunit is limiting in the extracts and that an excess
      of free CK2alpha has been produced in the transfected cells. Transfection of
      cells with CK2alphaE75E76 results in a CK2 activity of extracts that is 90%
      resistant to heparin demonstrating that a very large proportion of the CK2
      activity is derived from the expression of the exogenous mutant. In both the in
      vivo and in vitro systems, the sensitivity of CK2alphaE75E76 to heparin increases
      considerably when it forms part of the holoenzyme CK2alpha2beta2.

PMID- 11827175
TI  - Genes targeted by protein kinase CK2: a genome-wide expression array analysis in
      yeast.
AB  - Protein kinase CK2, a tetramer composed of two catalytically active (CK2alpha
      isoforms) and two regulatory (CK2beta isoforms) subunits, is suspected to have,
      among others, a role in gene transcription. To identify the genes targeted by
      CK2, the transcriptional effect of silencing the CK2 subunit genes in
      Saccharomyces cerevisiae (CK2alpha isoform genes: CKA1 and CKA2; CK2beta isoform
      genes: CKB1 and CKB2) was examined using genome-wide expression array analysis
      (oligonucleotide array chips). Silencing did not influence the overwhelming
      majority (5801) of the over six thousand open reading frames composing the yeast
      genome. Cells knocked-out for both CKA1 and CKA2 and plasmid-rescued by Cka1
      affected specifically at 2-fold discrimination level the transcription of 57
      genes, and when rescued by Cka2, the transcription of 118 genes. In CKB1/CKB2
      double knock-outs, transcription of 54 genes was specifically altered.
      Interestingly, aside overlaps between the gene spectra affected by CKA1 and CKA2
      silencing, there were overlaps also between those influenced by CK2alpha and
      CK2beta isoform silencing. The data indicate a distinct role of CK2 in gene
      transcription control, identify specific functional differences between the two
      catalytic subunits in gene targeting, and reveal independent effects by the
      regulatory subunits.

PMID- 11827176
TI  - Consequences of CK2 signaling to the nuclear matrix.
AB  - Protein kinase CK2 is recognized as one of the key cellular signals for cell
      growth and proliferation. Its nuclear targeting appears to be critical to its
      role in these functions. In the nucleus, nuclear matrix (NM) which plays a major
      role in growth-related activities is a primary locus for CK2 signaling. A variety
      of growth stimuli evoke a rapid translocation of the CK2 to the NM whereas
      removal of these factors has the opposite effect. These studies, employing
      various experimental models of cell growth (involving different growth
      stimulatory factors), have suggested that rapid shuttling of CK2 to the NM is a
      key feature of early growth control. By contrast, removal of growth-stimulatory
      factors leading to the loss of cell viability is associated with early loss of
      CK2 from the NM (and chromatin). This indicates that absence of CK2 from the
      nuclear compartment is contributory to induction of cell death via apoptosis,
      implying a protective role for CK2 against cell death. Here, we review the
      evidence that suggests that CK2 signaling in the NM is not only involved in cell
      growth but also in cell survival.

PMID- 11827174
TI  - Transcriptional coordination of the genes encoding catalytic (CK2alpha) and
      regulatory (CK2beta) subunits of human protein kinase CK2.
AB  - Little is known of how protein kinase CK2 genes are regulated, and it is unclear
      whether there are mechanisms of transcriptional coordination. Response elements
      present in the promoter sequences of the human catalytic (CK2alpha) and
      regulatory (CK2beta) subunit genes have been examined for the significance in
      transcriptional control using reporter gene assays, electrophoretic mobility
      shift assays, site-directed mutagenesis, ectopic protein expressions, and
      transcript assessments. Most strikingly, in both promoters the regions of highest
      transcriptional activity contain two adjoining, completely identical and
      conserved Ets1 response elements, and both the mutation of motifs and the
      overexpression of Ets1 affect significantly transcriptional activity. Also in
      common are Sp1 response elements that cooperate with Ets1, and Sp1 is
      phosphorylatable by CK2 holoenzyme but not by individual CK2alpha, the
      phosphorylation negatively affecting DNA binding. CK2alpha and CK2beta transcript
      levels and stoichiometries of mRNA species turned out quite constant in cultured
      cells despite progressing through various stages of proliferation and
      differentiation. The data seem to indicate transcriptional coordination of the
      human genes encoding CK2alpha and CK2beta based on an Ets1 double motif common to
      both genes cooperating with Sp1 motifs and amenable to negative feedback control
      by the gene products which, following complexation into CK2 holoenzyme, could
      phosphorylate Sp1 (and Ets1?) and thus downregulate transcription and contribute
      to the observed constant cellular CK2alpha and CK2beta transcripts situation.

PMID- 11827177
TI  - Localization of individual subunits of protein kinase CK2 to the endoplasmic
      reticulum and to the Golgi apparatus.
AB  - The protein kinase CK2 is composed of two catalytic alpha- or alpha'- and two
      regulatory beta-subunits. In mammalian cells there is ample evidence for the
      presence of individual CK2 subunits beside the holoenzyme. By immunofluorescence
      studies using peptide antibodies which allow us to detect the CK2alpha-, alpha'-
      and beta-subunits we found all three subunits to be co-localized with a 58 KDa
      Golgi protein which is specific for the Golgi complex. Subfractionation studies
      using dog pancreas cells revealed the presence of all three subunits of CK2 at
      the smooth endoplasmic reticulum (sER)/Golgi fraction whereas the rough
      endoplasmic reticulum (rER) harboured only the catalytic alpha- and alpha'
      subunits. We found that the microsomal preparation from dog pancreas cells
      contained CK2 which phosphorylated a CK2 specific synthetic peptide and which was
      heparin sensitive. Furthermore, we could immunoprecipitate the CK2alpha-subunit
      that exhibited a kinase activity which phosphorylated a CK2 specific substrate
      and which was heparin sensitive. Protease digestion experiments revealed that the
      CK2 subunits were located on the cytosolic side of the rER and the sER/Golgi
      complex. Thus, we could demonstrate an asymmetric distribution of the CK2
      subunits at the rER and sER/Golgi complex. Since the CK2alpha- and alpha'
      subunits exhibit a substrate specificity which is different from the CK2
      holoenzyme one might speculate that the asymmetric distribution of the CK2
      holoenzyme and the CK2 catalytic subunits may have regulatory functions.

PMID- 11827178
TI  - Visualization and molecular analysis of nuclear import of protein kinase CK2
      subunits in living cells.
AB  - We have generated fusion proteins between the subunits of CK2 and GFP and
      characterized their behaviour in living cells. The expressed fusion proteins were
      functional and interacted with endogenous CK2. Imaging of NIH3T3 cells expressing
      low level of GFP-CK2alpha or GFP-CK2beta showed that both proteins were mostly
      nuclear in interphase. Both CK2 subunits contain nuclear localization domains
      that target them independently to the nucleus. Once in the nucleus, both subunits
      diffused rapidly in the nucleoplasm. In mitotic cells, CK2 subunits were
      dispersed throughout the cytoplasm and were not associated to chromatin. Our data
      are compatible with the idea that each subunit can translocate individually to
      the nucleus to interact with each other or with important cellular partners.
      Understanding the molecular mechanisms which regulate the dynamic localization of
      CK2 subunits will be of central importance.

PMID- 11827180
TI  - A gene located at 72A in Drosophila melanogaster encodes a novel zinc-finger
      protein that interacts with protein kinase CK2.
AB  - Drosophila melanogaster protein kinase CK2 (DmCK2) is a Ser/Thr protein kinase
      composed of catalytic alpha and regulatory beta subunits associated as an
      alpha2beta2 heterotetramer. Using the two hybrid system, we have screened a
      Drosophila embryo cDNA library in order to identify proteins that interact with
      DmCK2alpha. One of these cDNAs encodes a novel previously undescribed zinc-finger
      protein, which we call ZFP47. ZFP47 interacts with DmCK2alpha but not with
      DmCK2beta, indicating that this interaction is specific for the catalytic subunit
      of CK2. In situ hybridization to polytene chromosomes indicates that the
      corresponding gene is located at the 72A interval of chromosome III. Sequence
      analysis indicates that ZFP47 contains a consensus site for phosphorylation by
      CK2, 4 C1H1-type zinc-fingers, and a bipartite nuclear localization signal.
      Consistent with the prediction of a site for phosphorylation by CK2, we
      demonstrate that ZFP47 is phosphorylated by CK2 purified from Drosophila embryos.
      These studies demonstrate that ZFP47 is a new physiological partner and substrate
      of CK2.

PMID- 11827181
TI  - Penetrating cardiac injuries: a complex challenge.

PMID- 11827182
TI  - Utilization of the walking oximetry test to allow safe ambulation after pulmonary
      resection.
AB  - Supplemental oxygen therapy after pulmonary resection can generally be tapered
      according to arterial blood gases at rest or pulse oximetry (SpO2). However,
      detecting exercise-induced oxygen desaturation can be difficult. We developed the
      walking oximetry test (WOT) so that thoracotomy patients could be rehabilitated
      without the risk of undetected ambulatory hypoxemia. The subjects were 58
      patients who had undergone pulmonary resection and could walk at the bedside,
      with oxygen at 3 l/min via a nasal cannula. Patients with a value of more than
      100 torr were allowed to walk with assistance for 6 min in the corridor. The
      oxygen flow rate was kept at 3 l/min and the walking pace was less than 50 m/min.
      SpO2 was determined using a wristwatch pulse oximeter. The test was stopped if
      the SpO2 fell below 90% or there was a score of 5 or more on the Borg scale
      (range 1-10). Oxygen desaturation occurred in six patients (10%) during the WOT.
      These patients underwent ambulatory training with sufficient oxygen
      supplementation and were then tested again. Patients whose SpO2 values remained
      higher than 90% and who showed no more than 5% desaturation were permitted to
      walk in the corridor with oxygen at 3 l/min via a nasal cannula. All these
      patients had a Borg score of 4 or lower. The WOT is a reliable, nonvasive method
      for detecting exercise-induced oxygen desaturation during ambulation after
      pulmonary resection.

PMID- 11827179
TI  - Identification and characterization of proteins that interact with Drosophila
      melanogaster protein kinase CK2.
AB  - D. melanogaster CK2 (DmCK2) is a highly conserved protein kinase that is composed
      of catalytic, alpha, and regulatory, beta, subunits associated as an alpha2beta2
      heterotetramer. In order to analyze the functions of CK2 in this metazoan model,
      we have used the two hybrid approach to identify interacting proteins. One of
      these cDNAs, DmA24, encodes a novel polypeptide with no homologs in GenBank, and
      is notable in that it contains a bipartite nuclear localization signal and two
      sites for phosphorylation by CK2. In situ hybridization to polytene chromosomes
      indicates that the DmA24 gene is located at the 61 D interval of chromosome II a
      region that also harbors 3 additional genes with similar structure. DmA24p
      interacts with DmCK2alpha, but not with DmCK2beta, demonstrating that this
      interaction is specific for the catalytic subunit of CK2. In addition, the
      protein is phosphorylated by the holoenzyme purified from Drosophila embryos.
      These studies identify DmA24p as a potentially new physiological partner of
      DmCK2. In addition, we also report the results of a large-scale screen that has
      identified a new set of DmCK2-interacting proteins. Most notable among these are
      Surf6, a nucleolar protein involved in RNA processing, and Spalt, a homeotic
      protein.

PMID- 11827183
TI  - Detection of IL-2 receptor gene expression in peripheral blood from renal
      transplant patients.
AB  - Cytokine monitoring is a potentially useful tool in the management of transplant
      patients. This study was conducted to analyze interleukin (IL)-1, tumor necrosis
      factor (TNF), IL-2, and IL-2 receptor gene expression by reverse transcriptase
      polymerase chain reaction (RT-PCR) in peripheral whole blood from healthy
      volunteers and patients who underwent laparotomy or renal transplantation. In the
      patients who underwent laparotomy, IL-1 and TNF expression was detected
      postoperatively, but IL-2 and IL-2 receptor expression was not. IL-1, TNF, and IL
      2 receptor gene expression was detected in all the renal transplant patients,
      including those with signs of rejection. No cytokine gene expression was detected
      preoperatively, pretransplant, or in the healthy volunteers. We were able to
      discriminate transplantation from laparotomy by the cytokine profile. These
      results indicate that our method may be a useful tool for the immunological
      monitoring of transplant patients.

PMID- 11827184
TI  - Changes in functional capacity after portal branch ligation in rats.
AB  - Preoperative portal branch embolization is performed to increase residual liver
      lobe volume so that posthepatectomy liver insufficiency associated with major
      hepatic resection can be prevented. Although it is essential to evaluate
      functional liver capacity after portal branch embolization. the timing of
      hepatectomy from this viewpoint remains unelucidated. The aim of this study was
      to clarify the optimal timing of hepatectomy after portal branch embolization. We
      evaluated the functional capacity of the liver after portal branch ligation (PBL)
      in rats, and studied the correlation between morphological and functional
      changes. Morphological changes were evaluated on the basis of the liver lobe
      weight ratio, and the proliferating cell nuclear antigen labeling index.
      Functional changes were evaluated by the indocyanine green disappearance rate and
      serum aminopyrine clearance as functional capacity. Although the total liver
      weight ratio remained unchanged after PBL, the unembolized lobe ratio increased
      significantly. Although functional capacity was minimal 2 days after PBL, it had
      recovered to the preoperative value by 8 days after PBL. The functional capacity
      of the liver after PBL was minimal around the cellular proliferative period but
      recovered thereafter. These findings suggest that major hepatectomy after portal
      branch embolization should be perfomed following the cellular proliferative
      period of the unembolized lobe.

PMID- 11827185
TI  - Successful reconstruction of extensive laryngotracheal strictures after
      inhalation burn injury: report of a case.
AB  - We report a rare case of long segmental laryngotracheal stenosis following
      inhalation burn injury. The patient presented 2 months after his injury with
      progressive stridor and dyspnea necessitating tracheostomy. A computed
      tomographic scan of the neck revealed stenosis extending from the vocal cords to
      the top of the sternum. Repair was successfully carried out with multiple
      surgical procedures employing hinge-flap closure tented with autogenous tissue.

PMID- 11827186
TI  - Periosteal chondroma of the rib: report of two cases.
AB  - We report two cases of periosteal chondroma of the rib, an extremely rare entity.
      The first case involved a 5-year-old boy who was admitted with pain and swelling
      around his left fifth rib. Surgery was performed in May 1999, and an 8 x 6 x 5 mm
      tumor was resected with the fifth rib. The second case involved a 39-year-old man
      with a 2-month history of cough who was referred to our department after a coin
      lesion had been detected on a chest roentgenogram. Physical examination on
      admission did not reveal any pain or tenderness. The rib tumor was resected along
      with the fourth rib by video-assisted thoracoscopic surgery and minithoracotomy
      in February 2000. The tumor was well encapsulated and consisted of an elastic
      hard mass measuring 22 x 15 x 13 mm. Both patients had an uneventful
      postoperative course and have remained well with no evidence of recurrence. Our
      review of the literature revealed only six previously documented cases of
      periosteal chondroma of the rib.

PMID- 11827188
TI  - Spontaneous esophageal perforation related to a duodenal ulcer with pyloric
      stenosis: report of a case.
AB  - This report describes a case of spontaneous esophageal perforation that was
      considered to be etiologically related to a duodenal ulcer with pyloric stenosis.
      The patient was a 54-year-old Japanese man who presented following the sudden
      onset of severe abdominal pain and dyspnea after an episode of vomiting. He had a
      history of duodenal ulcer. Computed tomography revealed an extremely dilated
      stomach containing abundant food residue, intraabdominal effusion, bilateral
      pleural effusion, and mediastinal emphysema, findings that strongly suggested
      esophageal perforation. Esophagoscopy confirmed perforation of the lower
      esophagus. Laparotomy revealed marked contamination, including food residue in
      the abdominal cavity, and a severely dilated stomach attributed to pyloric
      stenosis caused by a duodenal ulcer. A 2-cm longitudinal perforation was found on
      the right side of the lower esophagus. Because the patient's general condition
      was too poor to tolerate a one-stage operation (primary closure of the
      perforation, gastrectomy, and reconstruction), we initially performed
      decompression gastrostomy and control of the esophageal leakage with T-tube
      placement. Following the T-tube was removed 1 month later, distal gastrectomy and
      reconstruction of the gastrojejunostomy (Billroth II method) could be safely
      performed.

PMID- 11827187
TI  - An unusual combination of diaphragmatic hernias in a patient presenting with the
      clinical features of restrictive pulmonary disease: report of a case.
AB  - The combination of a Morgagni hernia and a paraesophageal hernia in adults is
      very rarely encountered in clinical practice. In fact, to our knowledge, only
      three cases of this condition, which is probably a coincidental occurrence, have
      been reported in the medical literature. We discuss the management of a 74-year
      old man found to have combined Morgagni and paraesophageal hernia who presented
      with clinical features of a restrictive pulmonary disease.

PMID- 11827189
TI  - Synchronous rectal and esophageal cancer associated with prurigo chronica
      multiformis: report of a case.
AB  - The skin lesions that appear in association with internal malignancies are called
      dermadromes or paraneoplastic cutaneous disorders. These skin changes
      characteristically develop with progression of the internal malignancy. A 75-year
      old Japanese man who had been diagnosed as having prurigo chronica multiformis, a
      form of dermadrome, 5 years previously was referred to our hospital for further
      investigation. On admission, numerous itchy red papules were present on the right
      side of the abdomen and the inner aspect of both thighs. Intensive screening for
      internal malignancies revealed advanced rectal cancer and early esophageal
      cancer. After surgical resection, the skin lesions improved without any
      treatment. To the best of our knowledge, this is the first case of synchronous
      double cancers associated with prurigo chronica multiformis.

PMID- 11827190
TI  - Primary localized amyloidosis of the small intestine presenting as an intestinal
      pseudo-obstruction: report of a case.
AB  - A 47-year-old man with primary amyloidosis confined to the small intestine is
      reported. Thickening of the folds and multiple polypoid protrusions were found in
      the duodenum by upper gastrointestinal endoscopy. Because the patient presented
      with a persistent intestinal pseudo-obstruction, partial jejunectomy was
      performed. Histological examination of the resected tissue revealed massive
      deposits of amyloid throughout the jejunal wall. Neither a predisposing condition
      nor any other sites of deposition were found, and primary amyloidosis of the
      small intestine was diagnosed. This rare form of amyloid deposition should be
      recognized so that an early diagnosis can be made.

PMID- 11827191
TI  - Implantation of rectal cancer cells in a fistula in ano: report of a case.
AB  - We report a case of implantation of tumor cells within a fistula in ano. A 36
      year-old man with a 16-year history of an anal fistula underwent an operation for
      rectal carcinoma. Three weeks later, the anal fistula was resected. A
      histological examination of the specimen showed atypical cells; moreover, rectal
      carcinoma had proliferated in the granulation tissue lying underneath the intact
      squamous epithelium. Because there was no continuity to the rectal carcinoma or
      the anal glands, we diagnosed implantation of rectal cancer cells in a fistula in
      ano.

PMID- 11827192
TI  - Ileoileal intussusception and ileal stricture associated with necrotizing
      enterocolitis in a premature infant: report of a case.
AB  - A 630-g male infant developed presumed necrotizing enterocolitis (NEC) after
      fungal enteritis that resulted in subsequent fungal septicemia associated with
      pneumoperitoneum on the 9th day of life. Urgent percutaneous Penrose drainage was
      required. During the operation on the 14th day, an ileoileal intussusception and
      an ileal stricture were found with perforations on each oral side of the lesions.
      The distinction between NEC and intussusception in premature infants when they
      coexist can be difficult, as these conditions share common symptoms. The relation
      between ischemic injury and dysmotility of the intestine is also discussed. The
      similarity of intrauterine fetal distress and NEC in premature infants, as seen
      in the present case of the intussusception associated with focal NEC, suggests
      that mesenteric and enteric vascular ischemia could be one trigger of
      intussusception in neonates.

PMID- 11827193
TI  - Successful resection of ampullary carcinoma in a father and adenoma in a daughter
      with familial adenomatous polyposis following detection by surveillance: report
      of two cases.
AB  - This report describes the successful resection of ampullary carcinoma in a 58
      year-old man and an adenoma in his 28-year-old daughter after they had undergone
      proctocolectomy for familial adenomatous polyposis (FAP). Both patients had been
      monitored by surveillance endoscopy once a year since their proctocolectomy. The
      father was found to have an ampullary adenoma 26 years after proctocolectomy, and
      ampullary carcinoma was detected 2 years later, for which pancreatoduodenectomy
      was performed. Histological examination of the specimen revealed an ampullary
      carcinoma, 2.5 x 1.7 cm, that had invaded the submucosal layer, but no lymph node
      metastasis was found. The patient's daughter underwent endoscopy, which showed an
      ampullary polyp 6 years after total colectomy. Endoscopic mucosal resection of
      the periampullary lesion was performed, and histological examination revealed a
      dysplastic tubular adenoma 0.6 x 0.4 cm in diameter. This report reinforces the
      importance of long-term periodic surveillance of patients with FAP by
      gastroduodenal endoscopy.

PMID- 11827194
TI  - Omental cyst: report of a case.
AB  - We report the case of an omental cyst, a rare type of abdominal cystic lesion
      that is difficult to diagnose preoperatively. A 43-year-old man with no clinical
      symptoms was admitted to our hospital for investigation of an abdominal cyst
      detected by ultrasonography (US). We performed diagnostic examinations including
      US, computed tomography, and magnetic resonance imaging. An omental cyst was
      diagnosed because of its position and connection to the surrounding tissues.
      Pathological examination of the surgical specimen revealed endothelial cells on
      its internal wall and colonies of lymphocytes, confirming a diagnosis of
      lymphangioma, which is the most common type of omental cyst.

PMID- 11827195
TI  - Carcinoid tumor of the spleen: report of a case.
AB  - Carcinoid tumors are uncommon tumors of the neuroendocrine system. They grow
      slowly and may remain silent for years before presenting with carcinoid syndrome.
      A diagnosis of asymptomatic carcinoid tumor is difficult. Wide resection of the
      primary tumor and metastatic lesions is the first choice of treatment. Primary
      carcinoid is sometimes distributed throughout the entire body, but it is rare in
      the spleen. We herein present a rare case of a symptomless carcinoid tumor that
      predominantly invaded the spleen with liver metastasis.

PMID- 11827196
TI  - Repair of false para-anastomotic aortic aneurysms using an endovascular stent
      graft technique in a patient with severe pulmonary disease: report of a case.
AB  - Conventional surgery for para-anastomotic aortic aneurysms is technically
      challenging, and is associated with high morbidity and mortality. This report
      describes the case of a patient with severe pulmonary diseases in whom false para
      anastomotic aortic aneurysms were successfully repaired using an endovascular
      stent graft technique.

PMID- 11827197
TI  - Colectomy for colon cancer via a 7-cm minilaparotomy.
AB  - We herein describe our technique for performing a colectomy to resect colon
      cancer via a 7-cm minilaparotomy using conventional surgical techniques and
      instruments. By moving the minilaparotomy wound laterally as well as either
      caudad or cephalad, the mobilization of the relevant segment of the bowel loop
      was thus made possible. To ensure an adequate visualization of the operative
      field during a dissection of the lymph nodes, an Omni-Tract retractor system was
      used. The division of the colonic mesentery, transection of the affected bowel,
      and bowel anastomosis were performed extracorporeally or at the level of the
      incision. This same operation was successfully performed in 102 patients with
      colon cancer. We conclude that a colectomy for colon cancer via a 7-cm
      minilaparotomy is an attractive alternative to a conventional full laparotomy in
      selected patients.

PMID- 11827198
TI  - Correlation of biofilm expression types of Staphylococcus epidermidis with
      polysaccharide intercellular adhesin synthesis: evidence for involvement of
      icaADBC genotype-independent factors.
AB  - IcaADBC-encoded proteins mediate synthesis of the intercellular polysaccharide
      adhesin (PIA), which is essentially involved in Staphylococcus epidermidis
      biofilm formation. Seventy S. epidermidis isolates were investigated for their
      ability to form biofilm and synthesize PIA in different growth media including
      trypticase soy broth obtained from Becton Dickinson (TSBBBL), or Oxoid
      (TSB(OXOID)), and TSB(OXOID) supplemented with 0.5% N-acetylglucosamine, and for
      the presence of icaADBC. Dependent on the medium used (TSB(BBL) or TSB(OXOID)),
      the isolates exhibited a differential expression of PIA and biofilm formation,
      with 51 (72.85%) and 34 (48.57%) being biofilm positive, respectively. Using
      these growth media four different expression phenotypes were differentiated:
      similar quantities of biofilm formation in both TSBBBL and TSB(OXOID) (11
      isolates, type A), significantly reduced biofilm expression in TSB(OXOID)
      compared to TSB(BBL) (23 isolates, type B), biofilm negative in TSB(OXOID) but
      biofilm producing in TSB(BBL) (17 isolates, type C) and biofilm negative in both
      media (19 isolates, type D). For all strains a biofilm-positive phenotype in a
      specific medium was closely linked to expression of PIA in that medium. All but
      one strain of expression type A-C and 7/19 expression type D strains were icaADBC
      positive. On the basis of restriction fragment length polymorphisms, the isolates
      were classified into two main icaADBC genotypes. There was no association between
      the observed biofilm-expression types and a defined icaADBC genotype. In the
      biofilm-negative S. epidermidis 5179, isolated from a ventriculo-atrial shunt
      infection, the insertion of IS257 interrupted the transcription of icaADBC,
      resulting in a PIA- and biofilm-negative phenotype. In all other icaADBC
      positive, biofilm-negative isolates no major alterations of the icaADBC gene
      locus were identified. Obviously, expression of icaADBC, PIA synthesis and
      biofilm formation are integrated into a complex regulatory network involving
      other determinants independent of icaADBC genotype. Inactivation of icaADBC by IS
      elements is apparently a rare cause of a biofilm-negative phenotype in clinical
      S. epidermidis isolates.

PMID- 11827199
TI  - Enterococcus spp. produces slime and survives in rat peritoneal macrophages.
AB  - Enterococcal clinical isolates were investigated for the ability to form biofilm
      on inert surfaces, as a measure of slime production, in an attempt to find new
      possible virulence factors for these microorganisms. This property was commonly
      found among Enterococcus faecalis. Also E. faecium isolates were able to form
      biofilm, although to a lesser extent; for this species, however, biofilm
      formation seemed more frequently associated with isolates from infection rather
      than with environmental strains or isolates from healthy individuals. Biofilm
      formation was strongly affected by the presence of an additional carbohydrate
      source in the medium, or by iron deprivation, indicating a role of slime for
      survival in stressful conditions. Slime-producing E. faecalis were able to
      survive inside peritoneal macrophages for extended periods compared to slime
      negative strains or to slime-positive bacteria grown in conditions depressing
      slime production. In particular, slime-producing and slime-negative cells showed
      a decrease of 1 and 2 log units, respectively, at 1 h after infection; slime
      negative cells were then rapidly killed, with clearance of bacterial cells at 24
      h. Slime-producing bacteria persisted up to 48 h, which was the last time point
      examined, as after that time viability of both infected and non-infected
      macrophages started to decline. Scanning electron microscopy observations showed
      the presence of abundant amorphous extracellular material, of possible
      polysaccharide nature, embedding bacterial cells to form a multilayered biofilm.
      Even in conditions not supporting biofilm formation, bacterial cells appeared
      capsulated, suggesting that capsule and slime might represent different
      structures. Genes belonging to the epa locus or to a putative icaA homolog did
      not seem to be involved in synthesis and export of slime.

PMID- 11827200
TI  - Kaposi's sarcoma-associated herpesvirus seroprevalence in selected german
      patients: evaluation by different test systems.
AB  - A total of 603 serum samples obtained from 12 different patient and control
      groups, including potentially cross-reactive sera, were tested for the presence
      of antibodies against Kaposi's sarcoma-associated herpesvirus (KSHV, HHV-8). The
      assays used were an inhouse immunofluorescence test (IFT) employing latent KSHV
      antigens and a prototype enzyme-linked immunosorbent assay (ELISA) coated with
      recombinant latency-associated KSHV nuclear antigen (LANA, open reading frame 73)
      and the K8.1 protein. Sera giving discrepant results were additionally tested
      with two commercial IFTs employing KSHV latent and lytic antigens, respectively.
      The low KSHV seroprevalence rate found in blood donors (3.0% by in-house IFT,
      2.0% by recombinant ELISA) was comparable to that found previously in Western
      European countries. The highest KSHV seroprevalence rates were found in patients
      with Kaposi's sarcoma (100% by both assays), followed by HIV-infected men without
      Kaposi's sarcoma (23.3% by in-house IFT and 17.8% by ELISA) and women (15.7% by
      in-house IFT and 13.7% by ELISA). Overall correlation between both assays was
      91.2%, with the highest rate of discordant results occurring in HIV-infected male
      subjects. Retesting of the 53 discrepant samples by the commercial IFTs revealed
      the best, albeit low, correlation between the in-house IFT and the commercial
      latent antigen IFT and poor correlations between the other assays. Apart from
      patients with autoimmune antibodies, there was no significant degree of non
      specific reactivity in either of the KSHV tests due to antibodies against Epstein
      Barr virus and human herpesvirus 6. Despite the lack of a "gold standard" for
      KSHV antibody detection, the fact that the results obtained overall agreed rather
      well indicates their suitability for conducting seroepidemiological studies.

PMID- 11827201
TI  - Evaluation of the new LCx HIV RNA quantitative assay: comparison with the Cobas
      Amplicor HIV Monitor assay.
AB  - In the present study we evaluated the performance of the new LCx HIV RNA
      quantitative kit (Abbott Laboratories, Delkenheim, Germany) for the quantitative
      detection of HIV-1 RNA in human plasma in comparison to the Cobas Amplicor HIV-1
      Monitor assay (Roche Diagnostics, Branchburg, N.J.), including samples containing
      a variety of HIV-1 subtypes. LCx and Cobas were compared using archived EDTA
      plasma samples collected from HIV-infected patients. Considering the lower limit
      of the linear range of 50 copies/ml, the detection rate of the LCx was 139 out of
      174 (79.9%) versus 131 out of 174 (75.3%) of the Cobas. Overall agreement was
      95.4% (166/174) at a cut-off of 50 copies. LCx and Cobas results on clinical
      samples were found linearly associated (r2 = 0.900) and strongly correlated (r =
      0.949). The mean viral load in the 174 frozen patient samples was 3.25 log10
      copies/ml by LCx compared to 2.71 log10 copies/ml by Cobas. Considering only
      samples with a viral load > or =50 copies/ml, the average difference was -0.132
      log copy/ml. Using a panel consisting of 9 plasma samples spiked with 9 different
      HIV-1 cultured isolates (A-H, and O) LCx detected the 9 subtypes with a high
      degree of precision, i.e., 9-33% coefficient of variation. As expected, the Cobas
      failed to detect the group O isolates. The results of the remaining samples
      showed a higher degree of variation (when testing four replicates of the subtype
      panel) than the LCx of 14.2-40.3%. Nevertheless, the results were comparable with
      the LCx data.

PMID- 11827202
TI  - Relationship between penicillin and cephalosporin resistance of Streptococcus
      pneumoniae strains and its inflammatory activity in the experimental model of
      meningitis.
AB  - Using a rabbit model of meningitis, we sought to compare the inflammatory
      activity induced by three pneumococcal strains with different susceptibilities to
      penicillin and cephalosporins, belonging to the serotypes 3, 6B and 23F at
      different inoculum sizes. These serotypes are prevalent in Western Europe and are
      believed to produce a moderate-to-severe cerebrospinal fluid (CSF) inflammatory
      response. Only minor differences were observed in the inflammatory activity
      evoked by the three strains in the subarachnoid space, and most were probably
      related to differences in bacterial counts. Infection by serotype 23F caused
      secondary bacteremia in all challenged animals. Our findings reinforce the
      concept that resistant pneumococci are not more virulent, a fact that should be
      taken into account when evaluating the efficacy of different anti-pneumococcal
      therapies. However, the frequent induction of secondary bacteremia by the
      resistant serotype 23F requires further study.

PMID- 11827203
TI  - Detection of Chlamydophila pneumoniae DNA in peripheral blood mononuclear cells
      of blood donors in the north-east of Italy.
AB  - Recent studies have implicated Chlamydia pneumoniae (now Chlamydophila
      pneumoniae) in the pathogenesis of atherosclerosis and demonstrated its presence
      within human peripheral blood mononuclear cells (PBMCs). In this study the
      presence of C. pneumoniae DNA was assessed, using nested PCR, in PBMCs from 169
      active blood donors as a function of age, of specific antibodies and C-reactive
      protein. The results obtained demonstrated a high degree of global positivity
      (46.15%), which was higher in females (52%) than in males (43.7%).
      Seroepidemiological studies showed a high percentage of positivity both in
      subjects positive by PCR (65.91%) and negative by PCR (71.74%). The clinical
      implication of such finding are under study.

PMID- 11827204
TI  - Binding inhibition of type 1 fimbriae to human granulocytes: a flow cytometric
      inhibition assay using trivalent cluster mannosides.
AB  - The binding of type 1 fimbriae from Escherichia coli to vital human neutrophilic
      granulocytes was inhibited by synthetic trivalent cluster mannosides. Binding of
      type 1 fimbriae was measured in a flow cytometric assay. Based on the molarity of
      mannosyl residues, the clusters exceed the inhibitory potency of methyl alpha-D
      mannoside by a factor of more than 1,000 and the inhibitory potency of p
      nitrophenyl alpha-D-mannoside by a factor of more than 10. The inhibition studies
      indicate that the trivalent cluster mannosides are very potent inhibitors of the
      binding of type 1 fimbriae to human neutrophilic granulocytes. Based on their
      defined structure, cluster mannosides are well suited for characterizing the
      molecular interactions of mannose-sensitive fimbriae with their cell membrane
      receptors.

PMID- 11827205
TI  - Protection against translocating Salmonella typhimurium infection in mice by
      feeding the immuno-enhancing probiotic Lactobacillus rhamnosus strain HN001.
AB  - The probiotic lactic acid bacterium Lactobacillus rhamnosus (strain HN001) is
      known to stimulate enhanced innate and acquired immune responses in mice.
      following oral delivery. Here, the ability of HN001 to confer immune enhancement
      and protection against an oral challenge of Salmonella tYphimurium was
      investigated. HN001-fed and non-probiotic-fed control BALB/c mice were challenged
      with either a single dose of S. typhimurium (ATCC strain 1772), or with five
      repeated daily doses of the pathogen; post-challenge clinical, behavioural,
      bacteriological and immunological parameters were assessed. Mice began to show
      ostensible signs of infection 3-4 days following the initiation of Salmonella
      challenge, and the first mortalities were observed after 6 days. Following single
      dose Salmonella challenge, HN001-fed mice maintained a higher mean pre-mortality
      general health score than control mice; retained significantly greater food and
      water intake and weight gain, produced higher titres of serum and intestinal
      tract anti-Salmonella antibodies, and showed greater overall survival of
      infection (27/30 mice surviving at 21 days post-challenge, compared to 2/29 in
      the control group). Following repeated-dose Salmonella challenge, HN001-fed mice
      had significantly lower mean pathogen burdens in visceral organs (spleen, liver)
      compared to controls, and additionally, blood and peritoneal leucocytes obtained
      from HN001-fed mice exhibited significantly higher ex vivo phagocytic capacity
      compared to control-mice. This study affirms that Lb. rhamnosus strain HN001
      displays immuno-enhancing properties in S. typhimurium-infected mice, and
      demonstrates that oral delivery of this probiotic can promote increased
      protection against a highly virulent enteric bacterial pathogen.

PMID- 11827206
TI  - Relationships within the Proteobacteria of plant pathogenic Acidovorax species
      and subspecies, Burkholderia species, and Herbaspirillum rubrisubalbicans by
      sequence analysis of 16S rDNA, numerical analysis and determinative tests.
AB  - Sequence data for 16S rDNA of the type strains of Acidovorax avenae subsp.
      avenae, A. avenae subsp. cattleyae, A. avenae subsp. citrulli, A. konjaci and
      Herbaspirillum rubrisubalbicans were compared with GenBank library accessions of
      Burkholderia spp., Comamonas sp., Ralstonia solanacearum and Variovorax sp.
      Maximum Parsimony analysis produced two clusters: 1. Acidovorax spp., Comamonas
      sp., and Variovorax sp. (all in the Comamonadaceae), and 2. Burkholderia spp.,
      Ralstonia solanacearum, and Herbaspirillum rubrisubalbicans. Maximum Likelihood
      analysis produced only one cluster (of the Comamonadaceae). Using nutritional and
      laboratory tests, all Acidovorax spp., Burkholderia spp., and Herbaspirillum
      rubrisubalbicans were discriminated in distinct clusters at the species level,
      and could be identified by selected determinative tests. There were no phenotypic
      tests constituted as a circumscription of the genera and which permitted the
      allocation of strains to genera. Strain identification as species allowed
      allocation to genera only by inference. The nomenclatural implications of these
      data are discussed.

PMID- 11827207
TI  - Kinetic profile of the cellular lipid composition in an oleaginous Yarrowia
      lipolytica capable of producing a cocoa-butter substitute from industrial fats.
AB  - Cell growth, lipid accumulation and cellular lipid composition of Yarrowia
      lipolytica growing on mixtures of industrial fats containing stearic, oleic,
      linoleic and palmitic acid have been studied. During growth, the strain
      incorporated oleic and linoleic acids more rapidly than the saturated fatty
      acids. Relatively high lipid accumulation (up to 0.44 g of lipids per g of dry
      matter) was observed when stearic acid was included in the culture medium. In
      contrast, substrates rich in oleic acid did not favor cellular lipid
      accumulation. The accumulated lipids, mainly composed of triacylglycerols (45-55%
      w/w), demonstrated a different total fatty acid composition compared with that of
      the substrate; in all cases, the microorganism showed the unusual capacity to
      increase its cellular stearic acid level, even if this fatty acid was not found
      in high concentrations in the substrate. This permitted the synthesis of
      interesting lipid profiles with high percentages of stearic acid and non
      negligible percentages of palmitic and oleic acid, with a composition resembling
      that of cocoa-butter.

PMID- 11827209
TI  - Three new species of Candida from apple cider: C. anglica, C. cidri and C.
      pomicola.
AB  - Three new anamorphic ascomycetous yeasts are described: Candida anglica (type
      strain NRRL Y-27079, CBS 4262), Candida cidri (type strain NRRL Y-27078, CBS
      4241), and Candida pomicola (type strain NRRL Y-27083, CBS 4242). These three
      species were isolated from cider produced in the United Kingdom, and their
      identification was determined from unique nucleotide sequences in the species
      specific D1/D2 domain of large subunit (26S) ribosomal DNA. Phylogenetic analysis
      of D1/D2 sequences placed C. anglica near Candida fragi, C. cidri near Pichia
      capsulata, and C. pomicola in the Pichia holstii clade.

PMID- 11827208
TI  - Isolation and biochemical characterization of cell wall tight protein complex
      involved in self-flocculation of Kluyveromyces bulgaricus.
AB  - Flocculation of yeasts is a cell-cell aggregation phenomenon which is driven by
      interactions between cell wall lectins and cell wall heteropolysaccharides. In
      Sabouraud medium, Kluyveromyces bulgaricus was highly flocculent. Incubation of
      flocculent K. bulgaricus cells with EDTA or Hecameg led to extracts showing
      hemagglutinating and flocculating properties. Purification of the extracts by
      native PAGE gave two bands which allowed flocculation of deflocculated K.
      bulgaricus. Both bands with specific reflocculating activity were composed of
      five subunits, of which only three possessed weak reflocculating activity upon
      deflocculated yeast. The mixture of these three proteins allow the recovery of
      initial specific reflocculating activity of the complex. These three proteins,
      denoted p28, p36 and p48, presented, in their first 15 amino acids, homologies
      with glycolysis enzymes, i.e., 3-phosphoglycerate mutase, glyceraldehyde-3
      phosphate dehydrogenase and enolase, respectively. However, no such enzymatic
      activity could be detected in the crude extract issued from treatment with EDTA
      and Hecameg of flocculent yeast cells. When yeasts had grown in glucose poor
      medium, flocculation was drastically affected. The EDTA and Hecameg crude
      extracts showed weak reflocculating activity. After PAGE, the protein complexes
      did not appear in the EDTA extract, but they did appear in the Hecameg crude
      extract. These results suggest that: (i) self-flocculation of K. bulgaricus
      depends on the expression of different floc-forming protein complex, (ii) these
      proteins are galactose specific lectins showing homologies in their primary
      structure with glycolysis enzymes.

PMID- 11827210
TI  - The effect of polyamine biosynthesis inhibition on growth and differentiation of
      the phytopathogenic fungus Sclerotinia sclerotiorum.
AB  - We studied the effects of several polyamine biosynthesis inhibitors on growth,
      differentiation, free polyamine levels and in vivo and in vitro activity of
      polyamine biosynthesis enzymes in Sclerotinia sclerotiorum. Alpha
      Difluoromethylornithine (DFMO) and alpha-difluoromethylarginine (DFMA) were
      potent inhibitors of mycelial growth. The effect of DFMO was due to inhibition of
      ornithine decarboxylase (ODC). No evidence for the existence of an arginine
      decarboxylase (ADC) pathway was found. The effect of DFMA was partly due to
      inhibition of ODC, presumably after its conversion into DFMO by mycelial
      arginase, as suggested by the high activity of this enzyme detected both in
      intact mycelium and mycelial extracts. In addition, toxic effects of DFMA on
      cellular processes other than polyamine metabolism might have occurred.
      Cyclohexylamine (CHA) slightly inhibited mycelial growth and caused an important
      decrease of free spermidine associated with a drastic increase of free putrescine
      concentration. Methylglyoxal bis-[guanyl hydrazone] (MGBG) had no effect on
      mycelial growth. Excepting MGBG, all the inhibitors strongly decreased sclerotial
      formation. Results demonstrate that sclerotial development is much more sensitive
      to polyamine biosynthesis inhibition than mycelial growth. Our results suggest
      that mycelial growth can be supported either by spermidine or putrescine, while
      spermidine (or the putrescine/spermidine ratio) is important for sclerotial
      formation to occur. Ascospore germination was completely insensitive to the
      inhibitors.

PMID- 11827211
TI  - Isolation and characterization of an unusual 1-aminocyclopropane-1-carboxylic
      acid (ACC) deaminase gene from Enterobacter cloacae UW4.
AB  - A genomic library of the 1-aminocyclopropane-1-carboxylic acid (ACC) deaminase
      containing plant growth-promoting bacterium Enterobacter cloacae UW4 in pUC19 in
      Escherichia coli was screened for the ability to utilize ACC as a sole source of
      nitrogen. One of the clones that was isolated contained a plasmid with an insert
      of approximately 0.8 kb that conferred ACC deaminase activity. Sequence analysis
      revealed that this DNA fragment contains an open-reading frame of 696 nucleotides
      predicted to encode a protein of 232 amino acids, a member of the amidohydrolase
      protein superfamily, i.e., a deaminase that contains a mononuclear or binuclear
      metal center as compared to the canonical ACC deaminase which contains pyridoxal
      phosphate as a co-factor.

PMID- 11827212
TI  - Molecular differentiation of sibling species in the Galactomyces geotrichum
      complex.
AB  - PCR-analysis, multilocus enzyme electrophoresis and molecular karyotyping were
      used to characterize 52 strains belonging to the genus Galactomyces. The
      resultant data revealed that a PCR method employing the universal primer N21 and
      microsatellite primer (CAC)5 is appropriate for the distinction of four Ga.
      geotrichum sibling species, Ga. citri-aurantii and Ga. reessii. Better separation
      was achieved with the UP primer N21; each species displayed a specific pattern
      with very low intraspecific variation. We propose to use the primer N21 for the
      differentiation of the six taxa composing the genus Galactomyces. Multilocus
      enzyme electrophoresis revealed genetic homogeneity of each sibling species
      within the Ga. geotrichum complex. On the other hand, the four sibling species,
      having from 41 to 59% of nDNA homology and similar phenotypic characteristics,
      are clearly distinguished based on their electrophoretic profiles using two
      enzymes: mannose-6-phosphate isomerase (MPI) and phosphoglucomutase (PGM).
      Despite the same number of chromosomal bands, different karyotype patterns were
      found in Ga. geotrichum sensu stricto and its two sibling species A and B. Within
      each sibling species, chromosome length polymorphism was observed, in particular
      for small bands, allowing discrimination to the strain level.

PMID- 11827213
TI  - Molecular taxonomy and biodiversity of rock fungal communities in an urban
      environment (Vienna, Austria).
AB  - The diversity of fungal communities on three different historical monuments in
      the city of Vienna (Austria) was analyzed and compared to the fungal diversity of
      microfungi on rock in the original quarry located in a rural area (Zogelsdorf,
      Austria). The fungal strains isolated were characterized by morphology and the
      complete rock fungal community was identified based on molecular data, that is,
      by sequencing parts of the small ribosomal subunit (18S) and internal transcribed
      spacer region 1 (ITS1). The genera Coniothyrium, Epicoccum and Phoma were found
      to be dominant on monument and rock surfaces. Additionally, black yeasts such as
      Exophiala species and microcolonial fungi like Sarcinomyces and Coniosporium
      which hitherto were regarded as typical rock inhabitants in semi-arid
      environments are frequently found on all rock surfaces in Vienna. The
      biodiversity of the fungi in the urban environment was much higher than on the
      same rock type in a rural environment, this difference can be attributed to the
      elevated organic pollution in the city.

PMID- 11827214
TI  - Enzymes of the Entner-Doudoroff and pyruvate decarboxylation pathways in
      Zymomonas mobilis wild-type CP4 and mutant strains grown in continuous culture.
AB  - The osmotolerant Zymomonas mobilis strain suc40, (containing plasmid pDS3154
      inaZ), which is capable of producing simultaneously ethanol and ice nuclei
      protein, was cultivated in a chemically defined complete sucrose medium, as well
      as in a sugar beet molasses medium in continuous culture. The strain exhibited
      the normal Monod's relationship between biomass and dilution rate, and between
      growth substrate concentration and dilution rate. Specific activities of a number
      of enzymes that appear to control important steps in the metabolic flux of the
      Entner-Doudoroff and pyruvate decarboxylation pathways were investigated over a
      range of growth rates in steady state cultures. With the exception of glucose-6
      phosphate dehydrogenase and gluconate kinase, all of the enzymes exhibited a very
      similar pattern for the wild type Z. mobilis CP4 and for the osmotolerant
      mutants, independent of the media used; the enzyme patterns remained relatively
      constant over the studied growth range. The specific activity of glucose-6
      phosphate dehydrogenase was increased 2-fold by decreasing dilution rate in sugar
      beet molasses. The specific activity of gluconate kinase was 2-fold lower at
      medium growth rates compared with that at either low or high growth rates.
      Pyruvate kinase, pyruvate decarboxylase and alcohol dehydrogenase activities were
      significantly higher compared with those of the enzymes governing the early steps
      of the Entner-Doudoroff pathway. The present study, which was designed to
      determine the behaviour of important enzymes in sucrose metabolism of Z. mobilis
      suc40/pDS3154-inaZ grown in continuous culture showed that the microorganism
      required regulation of specific enzyme activities at the transcriptional level
      when sugar beet molasses were used as the growth medium.

PMID- 11827215
TI  - A convenient and rapid method for genetic transformation of E. coli with
      plasmids.
AB  - A convenient and rapid method for the genetic transformation of Escherichia coli
      with plasmids is proposed. By mixing the recipient cells and plasmid DNA and
      spreading them directly on selective medium plates containing Ca2+, the so-called
      'plate transformation' could achieve almost the same transformation efficiency as
      the classical transformation method with calcium. The whole protocol takes only
      about 2 min, its simplicity compared favorably, not only to the usual protocol,
      but also to all other documented modifications.

PMID- 11827216
TI  - Genetic variability of the postharvest pathogen Gilbertella persicaria:
      identification of randomly amplified polymorphic DNA (RAPD) markers correlating
      with (+) and (-) mating types.
AB  - Random amplified polymorphic DNA (RAPD) and isoenzyme polymorphisms among 16
      isolates of the postharvest pathogen Gilbertella persicaria were examined. Six
      different 10-bp primers were used to determine the extent of intraspecific
      genetic variability. Nine composite amplification types were identified. RAPD
      markers were obtained which correlated with the mating types of the G. persicaria
      isolates. The variability of the isoenzyme patterns was very low and no
      correlation was found between the isoenzyme markers and the mating abilities.
      When 80 single carbon substrates were tested in utilization assays, most of them
      were utilized uniformly by the 16 G. persicaria strains. However, some compounds
      elicited differences between the isolates representing the two mating types. Beta
      alanine (0.2%) has little effect on the germination of the sporangiospores of the
      (+) isolates, but inhibited the germination of (-) sporangiospores. Glycerol-1
      monoacetate supported the growth of both mating types, but at concentrations
      higher than 4% this was accompanied with a compact (colonial) growth for plus
      mating type isolates only.

PMID- 11827217
TI  - Bioprospecting for novel hydroxyoxylipins in fungi: presence of 3-hydroxy
      palmitic acid in Saccharomycopsis malanga.
AB  - Electron microscopy studies indicated that the major oxylipin 3-hydroxy palmitic
      acid (16:0) was associated with aggregating vegetative cells and formed a web
      like structure around these cells. Cross sections through this structure showed a
      hydrophilic outer layer and a more hydrophobic inner layer suggesting that the
      web-like structure is in fact tube-like micelles. This information sheds more
      light on the role of these hydroxyoxylipins in fungi.

PMID- 11827218
TI  - Rhodotorula lamellibrachii sp. nov., a new yeast species from a tubeworm
      collected at the deep-sea floor in Sagami bay and its phylogenetic analysis.
AB  - A new species of the genus Rhodotorula was isolated from a tubeworm
      (Lamellibrachia sp.) collected at a depth of 1156 m in Sagami Bay, Japan. Strain
      SY-89 had physiological properties quite similar to R. aurantiaca. Two
      phylogenetic trees, one based on internal transcribed spacer (ITS) regions and
      5.8S rDNA sequences and the other based on the D1/D2 region of the large subunit
      (26S) rDNA sequences, united strain SY-89 to the type strain of Sakaguchia
      dacryoides through a considerable evolutionary distance. Strain SY-89 was
      differentiated from S. dacryoides by the G+C content of the nuclear DNA and
      differences in the ability to utilize specific carbon and nitrogen compounds. The
      low complementarity of strain SY-89 DNA to that of the type strain of S.
      dacryoides confirmed that this strain was genetically unrelated to previously
      known species. The tubeworm isolates are described as R. lamellibrachii sp. nov.
      The type strain of R. lamellibrachii is strain SY-89 (= JCM 10907). R.
      lamellibrachii formed a cluster with Erythrobasidium hasegawianum, R. lactosa, S.
      dacryoides and Sporobolomyces elongatus on the ITS and 5.8S rDNA phylogenetic
      tree. These five species shared a signature sequence in 26S rDNA, although this
      relationship was not supported by phylogeny based on the D1/D2 region of 26S
      rDNA.

PMID- 11827220
TI  - Social psychological models of choice behavior and drivers' left turns.
AB  - ABSTRACT. The authors reanalyzed data from a simulated left-turn experiment (P.
      A. Hancock, J. K. Caird, S. Shekhar, & M. Vercruyssen, 1991) to test the adequacy
      of the nonlinear Gray-Tallman satisfaction balance model of choice behavior (L.
      N. Gray & I. Tallman, 1984) in predicting left turns. Participants (Hancock et
      al., 1991) were 40 experienced U.S. drivers who were exposed to simulated
      oncoming traffic; the size of the vehicle (motorcycle, compact vehicle, full
      sized vehicle, delivery truck), its speed (10-70 mph, or 16-112 kmph), and the
      intervehicle time gap (3-9 s) varied. Hancock et al. (1991) measured (a) the
      likelihood of a left turn and (b) the occurrence of a collision. The probability
      of a left turn was greater for larger intervehicle time gaps and for oncoming
      smaller vehicles traveling at higher speeds. The Gray-Tallman (1984) model
      explained 69% of the variation in turning versus 57% for a linear regression
      model. In making decisions people tend to treat the values and costs affecting
      choices in a multiplicative, rather than linear, fashion. The Gray-Tallman model
      also has the potential for incorporating, both theoretically and mathematically,
      an unlimited range of potential values and costs that may influence left turn
      decisions.

PMID- 11827219
TI  - Explaining own and others' behavior in a controversial issue: animal
      experimentation.
AB  - The authors investigated how 2 groups with different attitudes toward animal
      experimentation-researchers who conducted animal experiments and members of
      animal welfare organizations who protested against animal experiments--made
      attributions for the behavior of the opposing group. The 2 groups showed an actor
      -observer effect, mentioning more internal causes for the opponents' behavior and
      more external causes for their own behavior. Both groups were able to take the
      other's perspective, resulting in a reversed actor-observer effect. The less
      involved participants followed the pattern of ratings of the group whose
      attitudes corresponded to their own. In particular, the participants with a
      negative attitude toward animal experimentation rated researchers' behavior as
      more internally caused than did those with a positive attitude. The results
      illustrated how the participants formed and defended attitudes in a social
      context.

PMID- 11827221
TI  - Self-esteem and performance on word tasks.
AB  - The authors investigated word-task performance of 192 postgraduate Indian women,
      grouped according to high or low self-esteem, after different causal attributions
      for failure. The subsequent performance of the low-self-esteem (LSE) participants
      improved after reattribution training. When the LSE participants were induced to
      attribute their prior failure to external causes, the external attribution not
      only reduced their natural tendency toward self-blame but also broke the self
      defeating cycle, thereby enabling them to improve their subsequent performance.

PMID- 11827222
TI  - Power and gender influences on responsibility attributions: the case of
      disagreements in relationships.
AB  - In a sample of 156 college students (74 men and 82 women), the authors examined
      the influences of power status and gender on responsibility attributions and
      resolution choices during disagreements in personal relationships. The
      participants read vignettes in which relationship partners disagreed; then the
      participants placed themselves in the situations depicted and reported their
      perceived responsibility and resolution choices. The participants were randomly
      assigned to 1 of 2 power-status conditions (you have/your partner has greater
      power in the situation). Power status was based on resource power (i.e., a
      monetary inheritance) or on perceived power (i.e., financial knowledge). The
      authors tested 2 alternative power-status hypotheses (justified benefits/rights
      and ability/accountability) and 1 gender hypothesis. The results supported both
      power-status hypotheses. In addition, the men's and the women's responsibility
      attributions and resolution choices (i.e., adhering to their own wishes or
      deferring to their partner's wishes) revealed differential dependence on the type
      of power held by the person with greater situational power. The authors suggest
      issues further research concerning how situational differences in socially based
      expectations (e.g., power status and gender) may affect conflicts within
      relationships.

PMID- 11827223
TI  - Personality attributes of volunteers and paid workers engaged in similar
      occupational tasks.
AB  - The authors' primary aim was to determine whether Australian volunteers and paid
      workers who were engaged in similar activities differed on aspects of a 5-factor
      model of personality. Their secondary aim was to determine whether personality
      attributes were similar between volunteers involved in different activities. The
      participants were 36 volunteer food preparers, 38 paid food preparers, and 31
      volunteer firefighters. Each participant completed a personality inventory (P. T.
      Costa & R. R. McCrae, 1992) and a brief demographic questionnaire. As predicted,
      the volunteer food preparers were more agreeable and extraverted than were their
      paid counterparts. The two volunteer groups differed only on the personality
      facet of assertiveness. The results support the existence of a constellation of
      traits that constitute a volunteering disposition; such traits may be relatively
      stable across time and situations. These results have scientific and practical
      implications for the literature on volunteering.

PMID- 11827224
TI  - Individual versus collective responses to membership in a low-status group: the
      effects of stability and individual ability.
AB  - To test predictions of social identity theory (SIT; M. A. Hogg & D. Abrams, 1988;
      H. Tajfel & J. C. Turner, 1979) and the 5-stage model (FSM; D. M. Taylor & D. J.
      McKirnan, 1984) concerning reactions to membership in a low-status group, the
      authors led 112 pupils to believe that another (anonymous) class outperformed
      their class. In an overall permeable and legitimate intergroup context, the
      authors manipulated the stability of the low group status and the individual
      ability of the group members. Contrary to SIT and FSM, the pupils generally
      favored collective normative action. Individual mobility was preferred only by
      group members, especially boys, with high individual ability who thought that the
      low status of their group was stable. The results support FSM assumptions (a)
      that individual ability is a powerful determinant of intergroup behavior but (b)
      that one should consider its impact in combination with perceived stability.

PMID- 11827225
TI  - Gender and speech rate in the perception of competence and social attractiveness.
AB  - The authors' hypotheses were that (a) listeners regard speakers whose global
      speech rates they judge to be similar to their own as more competent and more
      socially attractive than speakers whose rates are different from their own and
      (b) gender influences those perceptions. Participants were 17 male and 28 female
      listeners; they judged each of 3 male and 3 female speakers in terms of 10
      unipolar adjective scales. The authors used 8 of the scales to derive 2 scores
      describing the extent to which the listener viewed a speaker as competent and
      socially attractive. The 2 scores were related by trend analyses (a) to the
      listeners' perceptions of the speakers' speech rates as compared with their own
      and (b) to comparisons of the actual speech rates of the speakers and listeners.
      The authors examined trend components of the data by split-plot multiple
      regression analyses. In general, the results supported both hypotheses. The
      participants judged speakers with speech rates similar to their own as more
      competent and socially attractive than speakers with speech rates slower or
      faster than their own. However, the ratings of competence were significantly
      influenced by the gender of the listeners, and those of social attractiveness
      were influenced by the gender of the listeners and the speakers.

PMID- 11827226
TI  - Thromboembolic prophylaxis for patients with a fracture of the proximal femur.
AB  - Patients with a fracture of the proximal femur are at high risk for
      thromboembolic complications necessitating some form of preoperative and
      postoperative thromboembolic prophylaxis. Despite the knowledge that patients
      with a proximal femur fracture are at particularly high risk for both deep venous
      thrombosis and pulmonary embolism, there is no consensus on which strategy is
      most effective at preventing thromboembolic events in this patient population.
      The pathophysiology and associated risk factors for thromboembolic complications
      in this patient population are discussed. We present a review of studies that
      address the efficacy and safety of both mechanical and pharmacological methods of
      thromboembolic prophylaxis to assist the orthopedic surgeon in selecting among
      the different modalities available for thromboembolic prophylaxis.

PMID- 11827227
TI  - Anterior locking screw plate fixation for cervical spondylosis.
AB  - Thirty consecutive patients with significant cervical spondylotic myelopathy or
      radiculopathy were treated with anterior decompression, autologous iliac crest
      graft, and titanium hollow screw plate (THSP). Eight patients had 1 previous
      surgery, and 1 patient had 2 previous surgeries. Satisfactory fixation was
      achieved intraoperatively in all instances. At time of final follow-up, graft
      incorporation was noted in all instances. There were 4 complications: 2
      superficial infections, treated nonoperatively; 1 case of dysphagia, which
      resolved; and 1 case of spasmodic torticollis, which resolved. The THSP system
      allowed immediate stabilization of the involved cervical levels and facilitated
      reliable fusion.

PMID- 11827228
TI  - Ischial bursal chondromatosis.
AB  - A right ischial ulcer recurred after 6 months in a 79-year-old man with a history
      of recent hip fracture and Girdlestone procedure. Soft-tissue calcification was
      detected radiographically. The mass, hyperplastic bursal tissue with chondroid
      metaplasia, was excised. Bursal osteochondromatosis is reviewed.

PMID- 11827229
TI  - Lower extremity traction pins: indications, technique, and complications.
AB  - The placement of pins in the lower extremity for the purpose of skeletal traction
      is a basic skill required by an orthopedic surgeon. These pins are primarily used
      for the management of fractures and dislocations. Although simple, the insertion
      and care of these pins can be accompanied by severe complications including
      damage to neurovascular structures, physeal injury, ligamentous insult, fracture,
      and infection. We review the techniques of pin insertion at the distal femur,
      proximal tibia, and calcaneus to provide a foundation for residents and
      attendings alike so that unnecessary complications may be avoided and proper
      placement ensured.

PMID- 11827230
TI  - Extraction of an intra-articular bullet fragment from the subtalar joint: the
      "drill, tap, and extract" method.
AB  - The necessity of extracting intra-articular bullet fragments is well documented
      in the orthopedic literature. A case of the removal of a retained bullet fragment
      lodged within the subtalar joint and calcaneus is presented. The bullet fragment
      was drilled and tapped with small-fragment instruments and was readily removed.
      This technique is relatively easy to perform and may be used when bullet
      fragments are imbedded in osseous or intra-articular sites that are distant from
      the entrance wound.

PMID- 11827231
TI  - Workplace anger and aggression: informing conceptual models with data from
      specific encounters.
AB  - Workplace aggression is typically assessed by reports of the frequency of
      aggressive behaviors aggregated across incidents. Relations tested using such
      assessments are limited in the information they can provide about the operation
      of aggression within the context of a specific encounter. Analysis of data from
      structured interviews and questionnaire reports of employee experiences of
      specific workplace aggression incidents (as the target and as the aggressor)
      examine a variety of perceived antecedents, aggressive behaviors, and outcomes.
      Results suggest a variety of organizational, job-related, and personal
      antecedents, such as job stress and conflicts, and job-related outcomes, such as
      dissatisfaction. These data provide insight into the patterning of aggressive
      behaviors within an encounter and suggest an escalatory pattern. Data suggest
      relations between the severity of an aggressive encounter and the negativity of
      employee outcomes.

PMID- 11827232
TI  - A threat-appraisal perspective on employees' fears about antisocial workplace
      behavior.
AB  - This article uses a threat-appraisal model to examine the antecedents and
      consequences of antisocial behavior in an urban public school system. Teachers
      (compared with nonteachers) and middle and high school employees (compared with
      elementary school employees) reported higher levels of exposure to and fears
      about antisocial behavior. A path analysis demonstrated that threat appraisals
      partially mediate the relationship between antisocial behavior and job
      satisfaction and indirectly affect turnover intentions. These effects were
      consistent across high- and low-contact job types and across elementary, middle,
      and high school employees. The authors used the threat-appraisal model to
      describe the consequences of different interventions and found empirical evidence
      for employee voice and security measures as intervening variables.

PMID- 11827233
TI  - The Tyohon Job Search Program in Finland: benefits for the unemployed with risk
      of depression or discouragement.
AB  - The impact of preventive interventions for the unemployed may vary depending on
      the context of the labor policies and benefit systems of the country where it is
      implemented. The Tyohon Job Search Program was based on a method developed in the
      United States for recently unemployed workers. This study examined outcomes of
      the intervention in the context of the European labor market for participants who
      had been unemployed for a longer period. A total of 1,261 unemployed Finnish job
      seekers participated in a randomized field study. At the 6-month follow-up, the
      program had a beneficial impact on the quality of reemployment, especially among
      those who had been unemployed for a moderate time period. The program also
      significantly decreased psychological distress.

PMID- 11827234
TI  - Testing a conservation of resources model of the dynamics of emotional labor.
AB  - This study uses S. E. Hobfoll's (1989) conservation of resources theory as a
      means of examining why emotional labor may or may not result in burnout. A model
      is developed that proposes that workers attempt to cope with role demands by
      performing surface or deep acting and that the effect of this expenditure of
      resources on worker burnout depends on the more immediate rewards of the service
      encounter and the application of internal and external resources specific to the
      needs at hand. This model is tested and confirmed using cross-sectional survey
      responses from 236 working adults. Research and practical implications are
      discussed.

PMID- 11827235
TI  - The web of coping resources and pathways to reemployment following a job loss.
AB  - Structural equation modeling analyses of data from 2 longitudinal community
      studies of recently laid-off workers examined the interrelationships and pathways
      from personal coping resources to job-search intensity and the extent and quality
      of reemployment at 2 follow-ups (at 6 months and at 12 or 24 months). In both
      studies, the proposed models for predicting reemployment and reemployment quality
      provided a good fit to the data with the same pattern of results, which
      demonstrated that job-search motivation increased reemployment at all follow-ups
      but did not affect reemployment quality. At both the 6- and 12-month follow-ups,
      level of depressive symptoms decreased the extent and quality of reemployment.
      The results also highlighted the dual role of financial strain, which on the one
      hand facilitates reemployment by increasing job-search motivation and job-search
      intensity and on the other hand inhibits it by increasing depressive symptoms.

PMID- 11827236
TI  - Sources of social support and burnout, job satisfaction, and productivity.
AB  - Social support has been identified as an important correlate of a variety of work
      outcomes. Support from different sources, including family, coworkers, and
      supervisors, was examined in 211 traffic enforcement agents (92 men, 119 women).
      Outcomes included subjective variables (burnout and job satisfaction) and an
      objective measure of productivity (number of summonses). Support was negatively
      associated with burnout and positively associated with satisfaction and
      productivity. A cluster of support variables accounted for 7% of the variance in
      burnout and productivity and 12% of the variance in job satisfaction. Family
      support was more closely associated with burnout than with satisfaction or
      productivity, whereas immediate supervisor support was related to satisfaction
      and productivity but not burnout. Results suggest that support may be associated
      with work-related outcomes through multiple pathways.

PMID- 11827237
TI  - Diabetes mellitus.

PMID- 11827238
TI  - Management of the diabetic foot: preventing amputation.

PMID- 11827239
TI  - Highlights from the annual scientific assembly: managing the stages of
      Alzheimer's disease--new management options.

PMID- 11827240
TI  - Group C streptococcal infection in a prosthetic joint.

PMID- 11827241
TI  - Leptomeningeal carcinomatosis in metastatic prostate cancer.

PMID- 11827242
TI  - Chronic pain and its management in primary care.

PMID- 11827243
TI  - Neuropathy: new concepts in evaluation and treatment.

PMID- 11827244
TI  - Concise update to managing adult diabetes.

PMID- 11827246
TI  - Diabetes coding.

PMID- 11827245
TI  - Diabetes mellitus. Medication update.

PMID- 11827247
TI  - Effects of once-daily and twice-daily dosing on adherence with prescribed
      glipizide oral therapy for type 2 diabetes.
AB  - BACKGROUND: We evaluated differences in adherence and persistence with prescribed
      therapy of once-daily (OD) dosing compared with twice-daily (BID) dosing of
      glipizide in patients with type 2 diabetes. METHODS: The study cohort was derived
      from a pharmacy benefit manager claims database. Patients new to extended-release
      gastrointestinal therapeutic system (GITS) and immediate-release glipizide
      therapy were identified and followed for 1 year. Adherence indices (AIs) were
      calculated and persistence curves were constructed. RESULTS: Adherence indices
      rates were 60.5% in the GITS OD cohort and 52.0% in the BID cohort. Rates of
      persistence at 12 months were 44.4% in the GITS OD cohort vs 35.8% in the BID
      cohort. CONCLUSION: Initiation of OD pharmacotherapy results in better adherence
      and persistence compared with a BID regimen, despite a greater daily pill burden
      in the OD cohort. These data suggest that dosing frequency exerts a greater
      impact on patient adherence and persistence than number of tablets per dose.

PMID- 11827248
TI  - Role of exercise for type 2 diabetic patient management.
AB  - BACKGROUND: Exercise is integral to the management of type 2 diabetes.
      Unfortunately, the majority of adults with type 2 diabetes do not engage in
      regular exercise. METHODS: Three hundred patients with type 2 diabetes were
      randomly selected from a patient pool of diabetic patients encountered in 1996 at
      the Department of Veterans Affairs Medical Center in New Orleans, Louisiana.
      Medical records from October 1996 to June 1999 were reviewed. Information about
      exercise, alcohol intake, smoking, medications, laboratory results, and other
      variables was extracted from medical records. Patients with mean glycosylated
      hemoglobin (HbA1c) < 8.0 (good diabetic control) were compared with those who had
      poor diabetic control (mean (HbA1c) > or = 8.0). The effect of exercise in the
      management of type 2 diabetes was assessed. RESULTS: After adjustment for other
      variables, patients without exercise had an odds ratio of 2.71 (95% CI, 1.38
      5.32) for poor diabetic control compared with patients with exercise.
      CONCLUSIONS: These findings suggest that exercise by itself is important for type
      2 diabetes management.

PMID- 11827249
TI  - Measuring outcomes of type 2 diabetes disease management program in an HMO
      setting.
AB  - BACKGROUND: There is a need to evaluate empirical disease management programs
      used in managing chronic diseases such as diabetes mellitus in managed care
      settings. METHODS: We analyzed data from 252 patients with type 2 diabetes before
      and 1 year after enrollment in a disease management program. We examined clinical
      indicators such as HbA1C, HDL, LDL, total cholesterol, diastolic blood pressure,
      and BMI in addition to self-reported health status measured by SF-36 instrument.
      RESULTS: All clinical indicators showed statistically and clinically significant
      improvements. Only vitality and mental health showed statistically significant
      improvements in health status. Weak to moderate significant correlation between
      clinical indicators and health status was observed. CONCLUSIONS: Disease
      management can be effective at making significant clinical improvements for
      participants in a mixed-model HMO setting. No strong relationship between
      clinical indicators and health status was found. Future research is needed using
      a more specific health status measuring instrument and a randomized clinical
      trial design.

PMID- 11827250
TI  - Attitudes of internal medicine physicians toward type 2 diabetes.
AB  - BACKGROUND: This study was designed to identify differences among internists in
      their attitudes about diabetes and how those attitudes influence practice
      behavior. METHODS: A cross-sectional study of 55 internists in an academic
      medical center was done using the Diabetes Attitude Scale (DAS-3), a valid and
      reliable measure of attitudes toward diabetes. RESULTS: Most respondents were
      white (89%), male (65%), and < or = 40 years old (85%). On the need for special
      training, internists were significantly different from the standardized norm for
      the DAS-3. Similar differences were observed on the seriousness of type 2
      diabetes, the value attached to "tight control," and patient autonomy.
      Differences by age, sex, and level of training were not significant. CONCLUSION:
      Regardless of age, sex, or level of training, internal medicine physicians have
      negative attitudes toward type 2 diabetes that require future educational
      interventions.

PMID- 11827251
TI  - Maternal estimates of neonatal birth weight in diabetic patients.
AB  - BACKGROUND: No consensus exists on estimation of birth weight or prediction of
      fetal macrosomia in the diabetic population. We compared intrapartum clinical,
      maternal, and ultrasonographic estimates of birth weight in diabetic patients.
      METHODS: Diabetic patients at term had clinical, maternal, and ultrasonographic
      estimations of fetal weight. The mean absolute error, standardized error, and
      percentage of estimates within 10% of actual birth weight were determined for the
      three estimates. Effects of maternal weight, parity, and recent ultrasonography
      were assessed, and statistical analysis was done. RESULTS: With 32 women
      enrolled, no statistical difference was seen among clinical (11%), maternal
      (8.8%), and ultrasonographic (8.0%) birth weight estimates. No difference was
      seen in accuracy of the three estimates. Estimates were within 10% of actual
      birth weight in 69% of clinical and maternal estimations and 75% of
      ultrasonographic estimations. Maternal weight, parity, and recent
      ultrasonographic evaluation did not affect accuracy of predictions. CONCLUSIONS:
      Intrapartum maternal estimation of fetal weight in diabetic patients is as
      accurate as clinical and ultrasonographic predictions.

PMID- 11827252
TI  - Diabetic foot: evaluation and management.
AB  - Diabetic foot disease in the form of ulceration, charcot joint fracture, and
      amputation affects 20% of patients with diabetes. This results in tremendous
      morbidity, mortality, and health care cost. The magnitude of this problem has
      been underrecognized by health care professionals. Impaired glucose control over
      a period of years affects peripheral nerve function by loss of protective
      sensation, muscle atrophy, foot deformity, and neuropathic fractures. Yearly foot
      examinations can identify risk factors. Regular nail care, callus removal, and
      education can prevent plantar ulceration. Protective footwear and custom
      orthotics improve function by reducing force and shear impact on the fragile foot
      and accommodate the patient's deformities. A cost-effective strategy of yearly
      comprehensive foot examinations, education, and appropriate interventions can
      improve both the quality and duration of life for those with diabetes mellitus.

PMID- 11827253
TI  - Amelogenin gene expression in porcine odontoblasts.
AB  - Amelogenin is the major organic component in the enamel matrix of developing
      teeth and plays an important role in enamel biomineralization. Amelogenin has
      been reported to be a specific secretory product of ameloblasts. In this study,
      we examined amelogenin gene expression in various cell layers prepared from a
      porcine permanent tooth germ using reverse transcription-polymerase chain
      reaction (RT-PCR). Amelogenin amplification products were detected only in the
      secretory ameloblast layer after 20 cycles of PCR. After 30 cycles of PCR,
      amelogenin amplification products were detected in secretory and maturation-stage
      ameloblasts and in odontoblasts. The relative levels of amelogenin gene
      expression in secretory and maturation-stage ameloblasts and odontoblasts were
      determined. Secretory ameloblasts expressed over 1000 times the level of
      amelogenin mRNA found in odontoblasts. Amelogenin gene expression in odontoblasts
      was confirmed in an erupted porcine permanent first molar, which has no
      ameloblasts. Amelogenin PCR amplification products were identified from 4
      different alternatively spliced transcripts in the ameloblast samples, and the
      same spliced forms were detected in the odontoblast samples.

PMID- 11827254
TI  - Differential and quantitative analyses of mRNA expression of glucosyltransferases
      from Streptococcus mutans MT8148.
AB  - Streptococcus mutans produces three glucosyltransferases, coded by gtfB, gtfC,
      and gtfD, whose cooperative action is essential for sucrose-dependent cellular
      adhesion. This cellular adhesion plays an important role in the formation of
      dental plaque and the initiation of dental caries. Since they bear genetic
      similarities and are large in size, differentiation of their gene expression has
      been difficult, and little is known about the dynamic process of gtf expression.
      Using a real-time reverse-transcription/polymerase chain-reaction, we determined
      the expression of each gtf. Under various conditions, the relative levels of
      transcription were gtfB > gtfD > gtfC. Sucrose enhanced gtfD expression, whereas
      it reduced that of gtfB and gtfC, suggesting the presence of independent
      promoters. Quantitative analyses demonstrated coincidence between the ratio of
      expression of each gtf and the ratio previously identified as optimal for sucrose
      dependent adhesion in vitro, suggesting that S. mutans produces GTF at an optimal
      ratio to adhere to the tooth surface.

PMID- 11827255
TI  - Contraction stress related to degree of conversion and reaction kinetics.
AB  - Polymerization shrinkage of composites bonded to cavity preparations generates
      stress on the tooth/restoration interface. The purpose of this study was to
      verify the influence of degree of conversion and speed of polymerization reaction
      on contraction stress. We prepared experimental composites with different curing
      rates by varying the concentration of inhibitor (butylated hydroxytoluene). We
      verified the effect of degree of conversion by submitting one of the composites
      to different photo-activation times. Contraction stress was monitored for 10
      minutes in a tensilometer. Fourier-transformed infrared spectrometry was used for
      assessment of the degree of conversion. Volumetric shrinkage was determined by
      means of a mercury dilatometer. Degree of conversion and volumetric shrinkage
      showed a non-linear relationship with energy density. Degree of conversion showed
      a pronounced influence on stress. Increased inhibitor concentration reduced
      curing rate and contraction stress in composites, without compromising the final
      degree of conversion.

PMID- 11827256
TI  - Bonding to Er-YAG-laser-treated dentin.
AB  - Er-YAG laser irradiation has been claimed to improve the adhesive properties of
      dentin. We tested the hypothesis that dentin adhesion is affected by Er-YAG laser
      conditioning. Superficial or deep dentin from human molars was: (a) acid-etched
      with 35% H3PO4; (b) irradiated with an Er-YAG laser (KaVo) at 2 Hz and 180 mJ,
      with water-cooling; and (c) laser- and acid-etched. Single Bond (3M ESPE) and
      Z100 composite (3M ESPE) were bonded to the prepared surfaces. After storage,
      specimens were tested in shear to failure. Bonded interfaces were demineralized
      in EDTA and processed for transmission electron microscopy. Two-way ANOVA
      revealed that conditioning treatment and interaction between treatment and dentin
      depth significantly influenced shear bond strength results. Acid-etching alone
      yielded shear bond strength values that were significantly higher than those
      achieved with laser ablation alone, or in combination with acid-etching. The Er
      YAG laser created a laser-modified layer that adversely affects adhesion to
      dentin, so it does not constitute an alternative bonding strategy to conventional
      acid etching.

PMID- 11827257
TI  - Dynamic viscoelasticity of soft liners and masticatory function.
AB  - Soft denture liners are used for edentulous patients to cushion functional
      forces. We hypothesized that the application of soft liners having viscoelastic
      properties would lead to the most marked improvement in masticatory function. The
      shear storage modulus (G'), shear loss modulus (G''), and loss tangent (tan
      delta) were determined for 6 materials by means of a dynamic viscoelastometer.
      Masticatory function of ten subjects was evaluated by measurements of maximum
      bite forces and chewing times and frequencies for 2 food samples, and by the use
      of visual analogue scales. The acrylic materials exhibited viscoelastic behavior,
      while the silicones exhibited elastic behavior. The improvement in masticatory
      function compared with hard resin was found to be in the order: acrylic permanent
      materials > silicone > acrylic temporary materials. The results suggest that the
      use of materials with higher tan delta and G' provides the most optimum
      masticatory function for patients requiring the provision of soft liners on their
      dentures.

PMID- 11827259
TI  - Comparison of volatile sulfur compound concentrations measured with a sulfide
      detector vs. gas chromatography.
AB  - The accuracy of the Halimeter, an inexpensive, simple instrument that measures
      total breath volatile sulfur compounds (VSCs), has not been adequately tested. We
      compared Halimeter measurements with those obtained with a specific and sensitive
      gas chromatographic (GC) technique. The Halimeter gave different, biexponential
      responses to a constant concentration of different VSCs: The relative response
      rate and sensitivity were hydrogen sulfide > methyl mercaptan > dimethylsulfide.
      The transient peak VSC concentration of oral samples was reached long before the
      sulfide detector fully responded. The GC measurement of initial total VSCs in
      breath samples was 2.7+/-0.48 times greater than the peak concentration of the
      Halimeter. However, the plateau phase measurement of the Halimeter was 25%
      greater than that of GC. While GC and Halimeter measurements positively
      correlated, appreciable differences were observed. In studies where relatively
      precise VSC measurements are required, GC is the preferable technique.

PMID- 11827258
TI  - A novel mutation in human PAX9 causes molar oligodontia.
AB  - Experimental and animal studies, as well as genetic mutations in man, have
      indicated that the development of dentition is under the control of several
      genes. So far, mutations in MSX1 and PAX9 have been associated with dominantly
      inherited forms of human tooth agenesis that mainly involve posterior teeth. We
      identified a large kindred with several individuals affected with molar
      oligodontia that was transmitted as an isolated autosomal-dominant trait. Two
      point linkage analysis using DNA from the family and polymorphic marker D14S288
      in chromosome 14q12 produced a maximum lod score of 2.29 at theta = 0.1. Direct
      sequencing of exons 2 to 4 of PAX9 revealed a cytosine insertion mutation at
      nucleotide 793, leading to a premature termination of translation at aa 315. Our
      results support the conclusion that molar oligodontia is due to allelic
      heterogeneity in PAX9, and these data further corroborate the role of PAX9 as an
      important regulator of molar development.

PMID- 11827261
TI  - Big events in a small world: the changing face of oral microbiology.

PMID- 11827260
TI  - Applying modern survival analysis methods to longitudinal dental caries studies.
AB  - Before the 1960s, tooth-specific caries risk was reported to be highest at 2 to 4
      years after eruption. We studied the tooth-specific caries risk in three
      contemporary age cohorts in Finland. All together, 4072 boys and girls were
      followed annually from age 6 to age 18+ years in three age cohorts born in the
      1960s, 1970s, and 1980s. We used a survival model and Bayesian inferential
      methods in the statistical analyses to establish the secular changes during this
      period. The analysis was based on the caries risk in individual teeth as a
      function of tooth age instead of summary measures, such as DMFS values. Our first
      finding was a marked overall decrease of caries. Moreover, analyses of the 1960
      and 1970 cohorts revealed that the risk in molar teeth was highest immediately
      after eruption; in the youngest cohort, however, the risks of individual teeth
      were so low that no such dependencies on tooth age could be established.

PMID- 11827262
TI  - Potentiation of tumor necrosis factor-mediated apoptosis of oral squamous cell
      carcinoma cells by adenovirus-mediated gene transfer of NF-kappaB inhibitor.
AB  - Oral squamous cell carcinoma (SCC) is a malignant tumor which is often resistant
      to cancer-therapy-mediated apoptosis. The stress-responsive transcription factor
      nuclear factor kappa B (NF-kappaB), which has been found to be associated with
      SCC development, plays an essential role in the suppression of tumor necrosis
      factor (TNF)-mediated apoptosis. Here, we report that an adenovirus-mediated gene
      transfer of NF-kappaB inhibitor, super-repressor I kappa B alpha (Adv-SR
      IkappaBalpha), blocked TNF-induced NF-kappaB activation and sensitized oral SCC
      cells to TNF killing. Additionally, we found that the inhibition of NFkappaB by
      Adv-SR-IkappaBalpha enhanced TNF-mediated caspase-8 and -3 activation. These
      results suggest that NF-kappaB activation is a general mechanism by which oral
      squamous carcinoma cells are resistant to TNF killing and provide a molecular
      basis for gene therapy of oral cancer by IkappaBalpha gene transfer in vivo.

PMID- 11827263
TI  - Dietary changes among cancer survivors.
AB  - Given the limited scientific knowledge about dietary factors that affect cancer
      recurrence, dietary guidelines for cancer survivors are similar to general
      recommendations on healthy eating. This study explored the patterns of and
      motivation for, dietary changes among cancer patients. We conducted in-person
      interviews with 143 cancer survivors who were chosen from a mail survey on
      complementary and alternative medicine among cancer patients. We applied
      qualitative analysis using the software package NUD*IST to sort and code the
      transcribed interviews. The majority of dietary changes reported by 69 cancer
      patients agreed with current nutritional recommendations, such as decreasing meat
      and fat intake and increasing the consumption of vegetables and fruits. However,
      many diet changers also reported the intake of herbal and vitamin supplements,
      many with unproven effects. The major themes for changing diet were hopes that
      nutrition would increase well-being, maintain health and prevent cancer
      recurrence and beliefs that foods that cause or prevent cancer should be avoided
      and increased, respectively. Many cancer patients use non-scientific reasons when
      deciding on dietary changes and supplement use. Increasing communication with
      health care providers may prevent the use of extreme diets, unproven and possibly
      harmful supplements and reduce exaggerated hopes related to the benefits of a
      particular dietary regimen.

PMID- 11827264
TI  - Some experiences of professional practice and beneficial changes derived from
      clinical supervision by community Macmillan nurses.
AB  - This is a report of an interpretative study that explored some 'lived
      experiences' of community Macmillan nurses as they recounted them during clinical
      supervision meetings. This discussion is concerned with serious illness, dying
      and bereavement and the potential of supervision to reach the 'life-world' of
      professional practice but also potential benefits for Macmillan nurses. Accounts
      of professional practice are considered in the context of clinical supervision
      meetings. Five nurses--four women and one man--undertook individual clinical
      supervision with the researcher for 6 months over three phases for 18 months in
      total. Meetings took place in the clinics and health centres in which the
      Macmillan nurses worked. The method of clinical supervision drew on and developed
      established ideas from the health science literatures to guide supervisory
      practice. A synthesis of psychoanalytic ways of thinking and existential
      phenomenology provided a framework for understanding the data. Five salient
      themes were identified as emerging from accounts of professional practice:
      Biographical Determinants, Compulsion, Existential Concerns, Empathic
      Insufficiency in the Organisation of Palliative Care and Empathic Attainment in
      the Organisation of Palliative Care. The study shows a need to consider
      structuring environments that both help and protect community Macmillan nurses
      and fellow workers. Methods of clinical supervision should be informed by and
      complement lived experiences of working with serious illness, dying and
      bereavement.

PMID- 11827265
TI  - Screening for depression in palliative care patients: a review.
AB  - Depression is a significant symptom for 25% of patients admitted to a palliative
      care unit, but many of these symptoms are not identified and therefore not
      treated. Reasons for failure to diagnose depression are misconceptions regarding
      low mood as being a normal part of a terminal illness and also the patients'
      reluctance to disclose their thoughts and feelings. Medical and nursing staff
      working within palliative care may also find difficulty in distinguishing between
      what could be called appropriate sadness and a treatable depressive illness. In
      an effort to improve the detection of depression, many professionals are using
      rating scales or tools in order to improve the diagnosis and treatment. This
      review discusses the complex issues of diagnosis of depression and highlights why
      certain tools may not be so useful or applicable in the palliative care
      population.

PMID- 11827266
TI  - Acute leukaemia or highly malignant lymphoma patients' quality of life over two
      years: a pilot study.
AB  - The aim of this study was, first, to investigate the quality of life and sense of
      coherence for acute leukaemia and malignant lymphoma patients at the start of
      treatment and over 2 years. A second aim was to compare questionnaire responses
      with patients' statements in open-ended interviews. A consecutive sample of 16
      patients responded to the Quality of Life Questionnaire (QLQ-C30), Lund
      Gerontological Centre questionnaire and the Sense of Coherence Scale at the start
      of treatment and after 12 and 24 months. The QLQ-C30 questionnaire was
      administered also after 4, 8, 16 and 20 months. Tape-recorded open-ended
      interviews were conducted every 4 months before the patients responded to the
      questionnaires. Quality of life (QoL) and sense of coherence were scored more
      highly at the beginning of treatment for patients who did not relapse, than for
      those who relapsed. This difference remained throughout the study period. There
      was no correspondence in responses between questionnaire and personal interviews,
      although the results from the interviews, in some aspects, validated the result
      from the QLQ-C30. Those patients who relapsed may have had different
      prerequisites or been in a worse position at the onset of the disease and,
      reasonably, they needed more compensatory nursing care. More knowledge about the
      correspondence between a person's perceived QoL when discussed in personal
      interviews compared with responses given in standardised QoL questionnaires is
      needed before any assumption about clinical relevance can be made.

PMID- 11827267
TI  - Caring for cancer patients: relatives' assessments of received care.
AB  - This study aims to find out what cancer patients' relatives regard as important
      factors of patient care. The concept of 'patient care' is defined as consisting
      of two domains: the content of health care professionals' action and health care
      professionals' way of performing that action. The sample consisted of 168
      relatives of cancer patients from oncological wards from all over Finland. The
      data was collected with a questionnaire. Nonparametric tests were used for
      statistical analysis. The results showed that relatives regarded both the content
      of care and the way in which it was provided as important. The most important
      factors were the professional skill and trustworthiness of staff members and the
      safety of care. Relatives regarded information about the patient's prognosis as
      less necessary than information about the patient's cancer, its treatment and the
      side-effects of treatment. Relatives were generally pleased with the standards of
      care received by patients. Satisfaction with the actions of health care
      professionals was highest on the dimensions of professionalism, professional
      skill, trustworthiness, and friendliness. Two-thirds of the relatives said the
      patient did not have a primary nurse. It was also mentioned that there was little
      encouragement for the patients to take part in decision-making concerning their
      care.

PMID- 11827268
TI  - Assessing risk factors for systemic fungal infections.
AB  - The incidence of invasive fungal infection has increased in recent years. Most
      infections are caused by Candida albicans and Aspergillus spp. but the emergence
      of other fungal infections is changing the spectrum of disease. Immunosuppression
      and breakdown of anatomical barriers such as the skin are the major risk factors
      for fungal infections. Health care workers encounter at-risk patients in various
      settings, including AIDS clinics and intensive care, transplantation and oncology
      units. Patients with prolonged and deep neutropenia (haematological malignancy
      patients) are most at risk and are therefore most likely to receive prophylactic
      therapy. Practical measures can be taken to avoid exposing the patient to fungi
      (air filtration, regular hand washing, avoiding plants and flowers) and
      antifungal agents can be administered to prevent systemic fungal infection. Most
      fungal infections have non-specific symptoms; this makes recognition of the signs
      and symptoms of the disease important but also makes diagnosis difficult and
      empirical treatment necessary. Some antifungal agents have limitations but new
      formulations will improve therapy and play a key role in future antifungal
      strategies.

PMID- 11827269
TI  - Coping with the onset of cancer: coping strategies and resources of young people
      with cancer.
AB  - A chronic illness, such as cancer, causes permanent changes in a person's way of
      life and their way of adapting to changes. The purpose of this study was to
      describe the coping strategies and resources of adolescents and young adults with
      cancer. The data were collected by interviewing adolescents and young adults aged
      16-22 (n = 14) who had had cancer for more than 2 months and who came to a
      university hospital for treatment or control check ups. The interview material
      was analysed by content analysis. Emotion-focused, appraisal-focused and problem
      focused coping strategies were used. The major coping strategies were social
      support, belief in recovery and getting back to normal life as soon as possible.
      The subjects discussed with health care providers their disease, its treatment
      and how they could cope with everyday life as well as their energy and will-power
      to cope. The family was the most important source of emotional support. Also,
      gaining knowledge about cancer and its treatment was a good coping strategy.
      Moreover, a positive life attitude, belief in one's own resources, belief in God,
      earlier life experiences and willingness to fight against the disease were
      resources for coping with cancer.

PMID- 11827270
TI  - Squamous carcinoma of the thyroid metastatic to the choroid: a report.
AB  - Cancers metastatic to the eye are the most common intraocular malignancies.
      Breast, lung and gastrointestinal malignancies are the most common to the eye,
      with others forming a smaller group. This communication presents a very rare case
      of a choroidal secondary from a squamous cell carcinoma of the thyroid.

PMID- 11827271
TI  - Cancer genetics.

PMID- 11827272
TI  - Quantitative structure-activity relationships for the inhibition toxicity to root
      elongation of Cucumis sativus of selected phenols and interspecies correlation
      with Tetrahymena pyriformis.
AB  - The comparative toxicities of selected phenols to higher plants Cucumis sativus
      were measured and the negative logarithm molar concentration of the root
      elongation median inhibition (IRC50) were derived. Quantitative structure
      activity relationships (QSARs) were developed to explore the toxicity influencing
      factors and for predictive purpose. The toxicity data, fell into two classes:
      polar narcosis and bio-reactive. For polar narcotic phenols, a highly significant
      two-parameter QSAR based on 1-octanol/water partition coefficient (logKow) and
      energy of the lowest unoccupied orbital (E(lumo)) was derived (IRC50 = 0.77 log
      Kow - 0.39E(lumo) + 2.36 n = 22 r2 = 0.89). The five bio-reactive chemicals
      proved to show elevated toxicity due to their typical substructure involved
      diverse reactive mechanisms. In an effort to model all chemicals, a robust
      multiple-variable QSAR combining logKow, E(lumo) and Qmax, the most negative net
      atomic charge, was developed (IRC50 = 0.65 logKow - 0.72E(lumo) + 0.23Qmax + 2.81
      n = 27 r2 = 0.94), indicating that hydrophobicity, electrophilicity and hydrogen
      bond interaction contribute mainly to the phytotoxicity. The toxicological data
      was compared with Tetrahymena pyriformis 2-d population growth inhibition
      toxicity (IGC50) and excellent interspecies correlations were observed both for
      the polar narcotics and for five reactive chemicals (for polar narcotics: IRC50 =
      0.95IGC50 + 1.07 n = 16 r2 = 0.89; for bio-reactive chemicals: IRC50 = 0.98IGC50
      + 2.19 n = 5 r2 = 0.97; and for all: IRC50 = 0.93IGC50 + 1.63 n = 21 r2 = 0.87).
      This suggested that T pyriformis toxicity could serve as a surrogate of C.
      sativus toxicity for phenols and interspecies correlation also could be
      established for reactive chemicals.

PMID- 11827273
TI  - System-level responses of lake ecosystems to chemical stresses using exergy and
      structural exergy as ecological indicators.
AB  - This paper presents the system-level responses of experimental lake ecosystems to
      three chemical stresses (acidification, copper and pesticide contamination) using
      exergy and structural exergy as ecological indicators. The results indicate that
      the doses or toxicity of the three chemical stressors contributed to changes in
      both exergy and structural exergy. Remarkable changes in exergy and structural
      exergy occurred under acidic conditions and in the presence of Dursban, 24D-DMA,
      permethrin, bifenthrin, Carbaryl, TCP, PCP, trichlorethylene, benzene, and high
      doses of Cu, oil, and hexazinone. This seemed to indicate that the subject
      ecosystems were seriously contaminated by these chemical stressors. For low doses
      of Cu, oil, atrazine, HCBP, and hexazinone, exergy and structural exergy were
      either unchanged or only slightly changed, suggesting that the lake ecosystems
      were not significantly impacted by these chemical stressors. Discussion of the
      relationships between ecosystem-level changes and structural and functional
      changes in stressed lake ecosystems indicates that the above-mentioned ecosystem
      level changes were in accordance with the changes in structure and function. The
      observed changes in exergy and structural exergy were also consistent with Odum's
      predictions of shortened food chains, reduced resource use efficiency, poor
      stability, low information, and high entropy in stressed aquatic ecosystems. The
      findings lead the authors to conclude that it is feasible for exergy and
      structural exergy to serve as ecological indicators when characterizing the
      system-level responses of experimental lake ecosystems to chemical stress. These
      results for experimental lake ecosystems would be extrapolated to actual lakes.

PMID- 11827274
TI  - Interactions between a polycyclic aromatic hydrocarbon mixture and the microbial
      communities in a natural freshwater sediment.
AB  - The toxicity of a polycyclic aromatic hydrocarbon (PAH) mixture was assessed on
      the indigenous microbial communities of a natural freshwater sediment. The fate
      and effects of the PAH mixture (phenanthrene, fluoranthene and
      benzo(k)fluoranthene) were studied over 28 days. Bacterial communities were
      described by bacterial counts (total bacteria and viable bacteria), and by some
      hydrolytic enzyme activities (beta-glucosidase and leucine-aminopeptidase), PAH
      concentrations were measured in the overlying waters and in the sediments. No
      effect of PAH was detected at 30 mg/kg for all bacterial parameters. At 300
      mg/kg, the quantity of total bacteria and the proportion of viable bacteria
      markedly decreased, compared to the control (0 mg PAH/kg). At 300 mg/kg, an
      increase of the beta-glucosidase activity and a decrease of the leucine
      aminopeptidase activity were observed. For all treatments, the
      benzo(k)fluoranthene concentration in the sediment was stable over 28 days
      whereas, in the same time, only 3-6% of the initial concentrations of
      phenanthrene and fluoranthene remained. This study shows that (1) PAH induce
      perturbations of sediment microbial communities in terms of density and
      metabolism (but not always as an inhibition), (2) indigenous bacteria of
      sediments might be used for toxicity assessment of specific organic pollutants,
      (3) native microorganisms of sediment seem to have a high capacity for PAH
      degradation, depending on the physico-chemical properties and the bioavailability
      of the substance encountered.

PMID- 11827275
TI  - Ecotoxicity of nickel to Eisenia fetida, Enchytraeus albidus and Folsomia
      candida.
AB  - Despite growing concern about the potential adverse effects of elevated nickel
      concentrations in the environment, only a few toxicity data are available for
      terrestrial invertebrates. Therefore, chronic toxicity of nickel was assessed for
      Eisenia fetida, Enchytraeus albidus and Folsomia candida, the three invertebrates
      for which standard test protocols are available. The 21 d EC50 for the cocoon
      production of E. fetida was 362 (241-508) mg Ni/kg dry wt. For the reproduction
      of E. albidus, a 42 d EC50 of 275 (217-346) mg Ni/kg dry wt was observed. The 28
      d EC50 for the reproduction of F. candida was 476 (347-671) mg Ni/kg dry wt. The
      obtained toxicity data were very similar to those of related species reported in
      literature. Although the presented data can be considered as a step forward in
      the assessment of the potential risks of nickel in terrestrial environments,
      further research is needed to evaluate the influence of soil parameters on the
      toxicity of nickel and to quantify the effect of ageing on bioavailability.

PMID- 11827276
TI  - Toxicity of 4-nonylphenol in spiked sediment to three populations of Chironomus
      riparius.
AB  - Nonylphenols (NPs) are the primary stable metabolites of alkylphenol
      polyethoxylates (APEs), a family of compounds widely used in industry and in some
      domestic products. As NPs accumulate in sediments in aquatic environments, the
      risk to benthic organisms needs to be assessed. In this study 4NP-spiked
      sediments were tested on larvae of the dipteran Chironomus riparius. First instar
      larvae obtained from populations at three different sources were used. To spike
      the sediments, an equilibration procedure between water and sediment was adopted
      to avoid the use of solvents. Lower 10-d LC50 values were determined for two
      populations of C. riparius from clean environments (315-465 and 315-350 microg g(
      1) d.w., respectively) than those of a strain deriving from a population
      collected in a polluted river (600-680 microg g(-1) d.w.). Larval growth always
      decreased with increasing 4NP concentration but without any defined trend. The
      results of this study suggest that tolerance to the toxicant can be developed in
      populations of polluted environments and that testing procedures should be
      standardised.

PMID- 11827277
TI  - Evaluation of toxicity of pesticides and their biodegradation products using
      human cells.
AB  - Juvenoids are biologically active compounds, of relatively low toxicity to
      humans, that efficiently inhibit the fertility of insects. However, little
      attention has been paid to the stability and toxicity of products that may be
      generated by their biodegradation in the ecosystem. This study describes a simple
      comparison of the toxicity of the active compound and its degradation products
      generated by aerobic soil microbial isolates. Surprisingly we have found that
      toxicity of a biologically active carbamate juvenoid N-[2-[4-(2,2-ethylenedioxy-1
      cyclohexylmethyl)-phenoxylethyl]carbamate (W328) was comparable with that of
      1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT). The toxic effect was
      evaluated using the determination of the ATP/ADP content and viability of HeLa S3
      cells exposed to various concentrations of the chemicals tested for various
      durations. DDT was used as a reference compound. Its toxicity was compared with
      two juvenile hormone analogs. The original compound, W328, was found to be the
      most toxic. The major product (W329) generated both by yeast isolates and the
      mixture of moulds lost its activity on reproduction of the tested insect. Its
      toxicity towards human cells was also decreased. Another two W328 degradation
      HPLC fractions exhibited significantly reduced toxicity compared to W328.

PMID- 11827278
TI  - The interactions of cetyltrimethylammonium with mitochondria: an uncoupler or a
      detergent?
AB  - The interactions of cetyltrimethylammonium (CTA) with mitochondria have been
      investigated. We confirm, as already observed in a previous paper, that this
      compound behaves as proton carrier (or uncoupler) of the oxidative
      phosphorylation, but evidences suggest that this compound enhances the membrane
      permeability to many other compounds such as sucrose. We conclude therefore that
      CTA as a detergent enhances membrane permeability to all ions including protons.
      Some evidences are also given that the inhibitory effect of CTA on the
      mitochondrial respiratory chain is a consequence of the swelling induced.

PMID- 11827279
TI  - The cytotoxic and genotoxic potential of surface water and wastewater effluents
      as determined by bioluminescence, umu-assays and selected biomarkers.
AB  - Two bacterial tests employing Photobacterieum phosphoreum (Microtox
      bioluminescence test) and Salmonella typhimurium TA 1535 pSK1002 (umu-assay) were
      evaluated to estimate the cytotoxic and genotoxic potential of water samples from
      the selected rivers in Germany as well as the primary and secondary effluents of
      some sewage treatment plants. Rainbow trout (Onchorynchus mykiss) were exposed to
      different concentrations (20-40%) of secondary effluent in the model online
      aquatic monitoring plant WaBoLu-Aquatox. The toxic potential of water samples
      from the exposure tanks was determined in two prokaryotic test systems and the
      biomarkers acethylcholinesterase (AChE) activity in muscle tissue and DNA
      unwinding assay in liver tissue of fish. Samples from the tested rivers showed no
      inhibition of the bioluminescence of P. phosphoreum or growth of umu-bacteria.
      Only primary effluent samples from the treatment plants at the Saale River
      inhibited the light emission or the growth of test bacteria by more than 20%. The
      induction ratio of umu-bacteria was in most of the river samples less than the
      threshold for genotoxicity (IR < 1.5). Only some samples from the Saale River,
      especially at sites downstream of secondary effluents caused genotoxic responses
      in the umu-assay. Samples of primary effluents contained the greatest genotoxic
      potential up to GEUI = 6 which was not detectable in samples of secondary
      effluents. A concentration range 20-40% secondary effluent inhibited AChE
      activity in muscle tissue and significantly increased DNA fragmentation in liver
      tissue of rainbow trout. In contrast, no cytotoxic or genotoxic responses in the
      umu-assay were caused by water samples. Both bacterial methods can be
      successfully used to analyse the cytotoxic and genotoxic response of industrial
      and domestic wastewater and to estimate the effectiveness of sewage treatment
      units. However, because of their low sensitivity and high susceptibility, they
      are not reliable as a single test for the detection of cytotoxicity and
      genotoxicity in surface water. The application of prokaryotic tests systems with
      biomarkers such as AChE activity and DNA fragmentation in different tissues of
      test organisms seems to be a useful combination for the assessment of cytotoxic
      and genotoxic potential in surface water and secondary effluent.

PMID- 11827280
TI  - Some factors influencing EROD activity in winter flounder (Pleuronectes
      americanus) exposed to effluent from a pulp and paper mill.
AB  - EROD (ethoxyresorufin-O-deethylase) activity was determined in winter flounder, a
      sediment-inhabiting and non-migratory fish species, living near a pulp and paper
      mill in Newfoundland in relation to temperature, gender, sexual maturity, and
      lesions in the liver. Samples of liver were taken from fish captured by SCUBA
      divers at 0 degrees C, 5 degrees C and 16 degrees C. Enzymic activity was
      detected in fish living only above 0 degrees C. Adult males and juvenile fish had
      higher levels of EROD activity than prespawning females at 5 degrees C.
      Macrophage aggregates only or occurring simultaneously with bile ductule
      hyperplasia and clear cell foci in the liver, did not impair EROD activity but
      necrosis had a negative effect. Results from this study indicate the importance
      of water temperature, gender, sexual maturity and liver pathology in assessing
      EROD activity of fish in biomonitoring programs.

PMID- 11827281
TI  - Mechanism-based quantitative structure-activity relationships for the inhibition
      of substituted phenols on germination rate of Cucumis sativus.
AB  - Comparative inhibition activity (GC50) of 42 structurally diverse substituted
      phenols on seed germination rate of Cucumis sativus was investigated.
      Quantitative structure-activity relationships (QSARs) were developed by using
      hydrophobicity (1-octanol/water partition coefficient, logKow) and
      electrophilicity (the energy of the lowest unoccupied molecule orbital, Eluma)
      for the toxicity of phenols according to their modes of toxic action. Most
      phenols elicited their response via a polar narcotic mechanism and a highly
      significant log Kow-based model was obtained (GC50 = 0.92 log Kow + 1.99, r2
      0.84, n = 29). The inclusion of E(lumo) greatly improved the predictive power of
      the polar narcotic QSAR (GC50 = 0.88 log Kow - 0.30E(lumo) + 1.99, r2 = 0.93, n =
      29). pKa proved to be an insignificant influencing factor in this study. Poor
      correlation with hydrophobicity and strong correlation with electrophilicity were
      observed for the nine bio-reactive chemicals. Their elevated toxicity was
      considerably underestimated by the polar narcotic logKow-dependent QSAR. The nine
      chemicals consist of selected nitro-substituted phenols, hydroquinone, catechol
      and 2-aminophenol. Their excess toxic potency could be explained by their
      molecular structure involving in vivo reaction with bio-macromolecules. Strong
      dissociation of carboxyl group of the four benzoic acid derivatives greatly
      decreased their observed toxicity. In an effort to model all chemicals including
      polar narcotics and bio-reactive chemicals, a response-surface analysis with the
      toxicity, logKow and E(lumo) was performed. This resulted in a highly predictive
      two-parameter QSAR for most of the chemicals (GC50 = 0. 70 logKow - 0.66E(lumo) +
      2.17, r2 = 0.89, n = 36). Catechol and 2,4-dinitrophenol proved to be outliers of
      this model and their much high toxicity was explained.

PMID- 11827282
TI  - Algal tests with soil suspensions and elutriates: a comparative evaluation for
      PAH-contaminated soils.
AB  - An algal growth inhibition test procedure with soil suspensions is proposed and
      evaluated for PAH-contaminated soil. The growth rate reduction of the standard
      freshwater green alga Pseudokirchneriella subcapitata (formerly known as
      Selenastrum capricornutum) was used as the toxicity endpoint, and was quantified
      by measuring the fluorescence of solvent-extracted algal pigments. No growth rate
      reduction was detected for soil contents up to 20 g/l testing five non
      contaminated Danish soils. Comparative testing with PAH-contaminated soil
      elutriates and soil suspensions showed that the suspensions had toxicity
      endpoints 2.5-3000 times lower than tests with the corresponding elutriates.
      Algal growth inhibition tests with soil suspensions are recommended for screening
      purposes as a supplement to elutriate testing. Experiments with a phenanthrene
      spiked soil, showed that the sorbed compound did not contribute to the toxicity.
      However, the soil did act as a reservoir for phenanthrene, allowing desorption to
      occur continuously during the algal test which maintained higher concentrations
      of phenanthrene in the dissolved phase. Phenanthrene-spiked soil incubated for 90
      days before algal testing, resulted in a reduction of the toxicity to P.
      subcapitata by a factor of 76 (from EC10 = 0.3 to 23.6 g soil/l). However, during
      this 90-day period the total concentration of phenanthrene in the soil decreased
      by 38% (from 322 to 199 mg/kg) indicating that phenanthrene in the aged soil had
      become less bioavailable.

PMID- 11827284
TI  - Bioaccumulation of toxic metals (Cr, Cd, Pb and Cu) by seeds of Euryale ferox
      Salisb. (Makhana) W.
AB  - The level of toxic metals Cr, Cd, Pb and Cu was determined in seeds, water and
      sediments collected from nine closed waterbodies of Darbhanga, north Bihar, used
      for cultivation of the edible aquatic macrophyte Euryaleferox Salisb. during
      harvesting season of the crop for two successive years (1996 and 1997). Seeds
      bioconcentrated appreciable amount of these toxic metals in the order Pb > Cr >
      Cu > Cd. The increased load of metal pollution due to domestic and municipal
      discharges threatened the habitats of the plant. The toxic metal contents in
      seeds were found positively correlated with the ambient concentration of metals
      in water and sediments. The importance of these findings has been discussed for
      national water resource economy of the country and human health perspectives.

PMID- 11827283
TI  - Effects of trichloroacetic acid on the nitrogen metabolism of Pinus sylvestris--a
      13C/15N tracer study.
AB  - Trichloroacetic acid (TCA) can be found in various environmental compartments
      like air, rain and plants all over the world. It is assumed that TCA is an
      atmospheric degradation product of volatile chloroorganic hydrocarbons. The
      herbicide effect of TCA in higher concentrations is well known, but not much is
      known about the phytotoxic effects in environmentally relevant concentrations. It
      can be shown in this study by using the 13C/15N stable isotope tracer technique
      that [13C]TCA is taken up by roots of two-year-old seedlings of Pinus sylvestris
      L. and transported into the needles. At the same time the effect of the substance
      on nitrogen metabolism can be analyzed by measuring the incorporation of 15NO3-
      into different nitrogen fractions of the plant. The more [13C]TCA incorporation,
      the higher the synthesis of 15N labelled amino acids and proteins is. These
      effects on the nitrogen metabolism are probably based on the activation of stress
      and detoxification metabolism. It has to be assumed that there is an influence
      on N metabolism of Pinus sylvestris caused by the deposition of environmentally
      relevant TCA concentrations.

PMID- 11827285
TI  - Effects of atmospheric exposure to naphthalene on xenobiotic-metabolising enzymes
      in the snail Helix aspersa.
AB  - Polycyclic aromatic hydrocarbons are xenobiotics whose elevated toxicity for
      living organisms requires to efficiently monitor air pollution, either by
      evaluating their levels in the environment, or by assessing their biological
      impacts on sentinel organisms. We investigated the effects of naphthalene
      exposure on some xenobiotic-metabolising enzyme activities in three organs of
      Helix aspersa. Particular activities depending on cytochrome P450
      (ethoxyresorufin O-deethylase, EROD; ethoxycoumarin O-deethylase, ECOD;
      pentoxyresorufin O-dealkylase, PROD) and associated with glutathione (glutathione
      S-transferase, GST; glutathione peroxidase, GPX; glutathione reductase, GR) were
      assessed. In control animals, the P450-dependent specific activities were
      distributed according to the range kidney > digestive gland > mantle cavity
      forming tissues (MCFT). Neither ECOD nor PROD activities could be detected in
      MCFT. In the two other organs, the major phase I activities were due to ECOD, the
      level of PROD being very low or null. The glutathione-associated activities
      showed comparable levels in the three organs, except GPX activity that was higher
      in the digestive gland. Naphthalene (NAP) exposure did not affect any activity in
      MCFT, but it significantly decreased EROD and ECOD activities in the kidney as
      opposed to their increase in the digestive gland, whereas PROD activities were
      not influenced by the treatment. Glutathione-dependent activities were not
      significantly affected by NAP exposure, except for GPX which activity diminished
      in the digestive gland. This study demonstrates that complex detoxification
      pathways should exist in Helix aspersa as in mammals and that they could be used
      as potential biomarkers of NAP exposure.

PMID- 11827286
TI  - Oxidative stress induced by HCH in Hydrilla verticillata (l.f.) Royle: modulation
      in uptake and toxicity due to Fe.
AB  - The effect of hexachlorocyclohexane (HCH) singly and in combination with iron was
      studied on chlorophyll, malondialdehyde, cysteine, total -SH contents and
      potassium ion leakage in the plants of Hydrilla verticillata. The effect of HCH
      was also studied on glutathione (reduced and oxidised) content and superoxide
      dismutase activity. The results showed an increase in malondialdehyde content and
      potassium ion leakage with increase in HCH concentrations, however, the presence
      of Fe played a protective role. The chlorophyll content was decreased with
      increase in HCH concentrations and exposure period. However, the chlorophyll
      content at 2 and 5 microg ml(-1) was significantly higher in HCH-treated plants
      as compared to HCH + Fe after 168 h, showing protective role of Fe. The results
      showed significant increase up to 1 microg ml(-1) in cysteine content with
      increase in concentrations in both the treatments. The total -SH content was
      increased with increase in concentrations in both the treatments. In HCH-treated
      plants, non-significant change was noticed in reduced glutathione (GSH) content
      however, oxidised glutathione (GSSG) content was increased significantly after
      168 h, indicative of oxidative stress. In addition, superoxide dismutase activity
      was increased non-significantly with increase in HCH concentrations. The
      accumulation of HCH singly and in presence of Fe was concentration- and duration
      dependent. The accumulation of HCH was decreased in presence of Fe at higher
      concentrations. In contrast, the accumulation of Fe was increased in presence of
      HCH at higher concentrations. The results showed that malondialdehyde content and
      potassium ions leakage are the primary responses of toxicity.

PMID- 11827288
TI  - Sister chromatid exchange and proliferative rate index in the longitudinal risk
      assessment of occupational exposure to pesticides.
AB  - At present, there are more than 1,000 chemicals classified as pesticides and many
      reports have shown that some of them have genotoxic properties. In the present
      longitudinal study, possible genetic damage on a population of workers
      occupationally exposed to a mixture of pesticides by using sister chromatid
      exchange (SCE) analysis has been evaluated. As an additional cytogenetic
      parameter, the proportion of lymphocytes that undergo one, two or three cell
      divisions as well as proliferative rate index have been determined. This study
      was performed on the exposed group of workers employed in pesticide production,
      simultaneously exposed to a complex mixture of pesticides (atrazine, alachlor,
      cyanazine, 2,4-dichlorophenoxyacetic acid, and malathion). The blood samples of
      the exposed subjects were collected in three different periods: before the
      beginning of the new pesticide production period, after 8 months of everyday work
      in the pesticide production, and 8 months after the removal of subjects out of
      the production. In all three samplings, the mean value of SCE and number of cells
      with high sister chromatid exchange frequency (HFC) in the exposed group was
      significantly higher in the comparison with the control group. There were no
      differences in the proliferative rate index (PRI) between the control and exposed
      group, regardless of the sampling period. In both groups examined, the majority
      of lymphocytes were found in the second cell division, following cultivation.
      These results suggest that the increase in the number of SCE found in the exposed
      subjects is not the result of either cytotoxic or epigenetic action of pesticide
      mixture, but chronic occupational exposure to mixture of pesticides.

PMID- 11827287
TI  - Toxicity monitoring and classification of endocrine disrupting chemicals (EDCs)
      using recombinant bioluminescent bacteria.
AB  - A recombinant bioluminescent Escherichia coli, DPD2794, containing the recA
      promoter region fused to luxCDABE originating from Vibrio fischeri was used for
      detecting genotoxicity caused by endocrine disrupting chemicals (EDCs) to cells.
      As well, several other recombinant bioluminescent bacteria, including TV1061,
      which is sensitive to protein damage (grpE::luxCDA BE), DPD2511, sensitive to
      oxidative damage (katG::luxCDABE), and DPD2540, sensitive to membrane damage
      (fabA::luxCDABE), were used for evaluating other possible modes of toxicity. It
      was found that the recombinant bacteria could monitor the toxic effect, not
      estrogenic effect, due to the presence of various EDCs through the measurement of
      bioluminescence (BL) and cell growth rate, which depend upon the type of toxicity
      occurring and which of the four strains was used. In addition, it was found that
      the damage caused by EDCs can be classified into several groups upon their
      mechanisms of toxic action.

PMID- 11827290
TI  - Relative sensitivity of one freshwater and two marine acute toxicity tests as
      determined by testing 30 offshore E & P chemicals.
AB  - Acute toxicity of 30 offshore E & P (Exploration and Production) chemicals was
      measured using the three standard test organisms Daphnia magna (freshwater
      cladoceran), Acartia tonsa (marine copepod) and Skeletonema costatum (marine
      diatom alga). Test chemicals included 20 water-soluble and 10 (partially) non
      soluble products. For 22 out of the 30 chemicals, the difference in sensitivity
      between the three tests varied within one order of magnitude. A very good
      correlation was found between the two marine tests (r = 0.96, P < 0.01, n = 30),
      and a correlation coefficient of r = 0.78 (P < 0.01, n = 30) was found between D.
      magna and both A. tonsa and S. costatum, individually. When the comparison of D.
      magna and A. tonsa sensitivity was based only on the water-soluble chemicals, a
      significantly higher correlation was obtained (r = 0.84, n = 20), indicating that
      the sample preparation method used for the (partially) non-soluble chemicals (the
      water accommodated fraction (WAF) method) induces additional variation between
      tests performed with different test media. (Partially) non-soluble chemicals are
      characterised by phase separation or precipitation at the concentrations used for
      testing. In a WAF-based test, each test concentration/exposure level is prepared
      separately, and following mixing and separation, only the water phase is used for
      testing. Toxicity is related to the amount of substance originally added to the
      mixing vessels. For 25 of the 30 chemicals, D. magna was found to be less
      sensitive than the marine copepod by a factor >2. The generally higher
      sensitivity of the marine toxicity tests compared to the Daphnia test emphasise
      the importance of using marine data for environmental hazard classification as
      well as for environmental risk assessment purposes.

PMID- 11827289
TI  - Prediction of mixture toxicity with its total hydrophobicity.
AB  - Based on the C18 Empore disk/water partition coefficient of a mixture,
      quantitative structure-activity relationships (QSARs) are presented, which are
      used to predict the toxicity of mixed halogenated benzenes to P. phosphoreum. The
      predicted toxicity of 10 other related mixtures based on the QSAR model, agree
      well with the observed data with r2 = 0.973, SE = 0.113 and F = 287.785 at a
      level of significance P < 0.0001. The joint effect of these chemicals is simple
      similar action and the toxicity of the mixtures can be predicted from total
      hydrophobicity and is independent of hydrophobicity of the components or the
      ratio of the individual chemicals.

PMID- 11827292
TI  - Studies on the accumulation and transformation of arsenic in freshwater organisms
      II. Accumulation and transformation of arsenic compounds by Tilapia mossambica.
AB  - Bioaccumulation and biotransformation of arsenic (As) compounds in freshwater
      Tilapia mossambica was investigated. The direct accumulation of As by T
      mossambica was proportional to the concentration of arsenicals in water. Small
      amounts of accumulated As were transformed to methylated As, including
      trimethylarsenic (TMA) species. Accumulation and transformation of As(III) by T.
      mossambica via freshwater food chain results in the transformation of As(III) to
      As(V) with little biomethylation of accumulated As. Approximately 90% of
      accumulated As was depurated to water.

PMID- 11827291
TI  - Studies on the accumulation and transformation of arsenic in freshwater organisms
      I. Accumulation, transformation and toxicity of arsenic compounds on the Japanese
      medaka, Oryzias latipes.
AB  - Accumulation, transformation and toxicity of arsenic compounds to Japanese
      Medaka, Oryzias latipes were investigated. For sodium arsenite [As(II)] and
      disodium arsenate [As(V)], the mean value for 7-day lethal concentration LC50 for
      O. latipes were 14.6 and 30.3 mg As/l, respectively. Direct accumulation of
      arsenic in O. latipes increased as a function of As(III) concentration in water.
      A small proportion of accumulated arsenic was transformed to methylated arsenic.
      As much as 70% of the total arsenic accumulated in tissue was depurated.
      Accumulation and transformation of As(III) by O. latipes in a simple freshwater
      food chain were also investigated. The transformation of As(III) to As(V) by
      organisms was more prevalent than biomethylation of accumulated arsenic in
      organisms of the three steps of the food chain.

PMID- 11827293
TI  - The toxicity of tri-substituted benzenes to the protozoan ciliate Spirostomum
      ambiguum.
AB  - The Spirotox test utilises a large ciliate protozoan Spirostomum ambiguum as a
      test organism. The goal of the present study was to evaluate the toxicity of tri
      substituted benzenes in the Spirotox test. Twenty-six organic compounds were
      tested in this study and included: dimethylphenols (DMPs), dichlorophenols
      (DCMs), trichlorobenzenes (TCBs), dichloroanilines (DCAs), dinitrophenols (DNPs),
      dinitroaniline (DNA), dinitrochlorobenzene (DNCB) and dinitrofluorobenzene
      (DNFB). The toxicity of the compounds tested varied almost four orders of a
      magnitude. DMPs and DCAs were the least toxic, whereas dinitro derivatives were
      the most toxic to S. ambiguum. When chlorine or fluorine atoms were replaced by
      amino or hydroxy substituents, the toxicity increased dramatically. The results
      of the Spirotox test were compared with three other bioassays that are widely
      used around the world: Microtox, Tetrahymena pyriformis and Daphnia magna. The
      Spirotox was less sensitive than these other bioassays for the majority of these
      compounds, with an exception found for the dinitro derivatives.

PMID- 11827294
TI  - Toxicity evaluation of reactive dyestuffs, auxiliaries and selected effluents in
      textile finishing industry to luminescent bacteria Vibrio fischeri.
AB  - The toxicity of 17 selected process effluents, 11 reactive dyestuffs and 8
      auxiliaries from a textile dyeing and finishing mill in Ayazaga, Istanbul, Turkey
      was evaluated by bioluminescence test using bacteria Vibrio fischeri in LUMIStox
      300. The EC20 and EC50 for auxiliaries, the EC20 for dyestuffs were determined.
      For selected process effluents GL-values, the dilution level at which a
      wastewater sample causes less than 20% inhibition, were examined. Our results
      demonstrate that the toxicity assessment with luminescent bacteria is effective
      and of practical use for chemicals applied in textile finishing industry with the
      limitation of the deep dark-colored dye bath samples and for the related
      effluents. Inhibition effects of numerous dyestuffs as well as auxiliaries to
      luminescent bacteria differed considerably with a range 5-600 mg l(-1) for EC20
      and 9-6930 mg l(-1) for EC50, respectively. Among 17 effluents, I sample
      exhibited high toxicity (GL = 100), 7 showed moderate toxicity (GL = 12-32), and
      9 had a GL-value <10 indicating a low or no toxicity.

PMID- 11827295
TI  - Degradation of bisphenol-A (BPA) in the presence of reactive oxygen species and
      its acceleration by lipids and sodium chloride.
AB  - In this study, (1) change in bisphenol-A (BPA) leached from polycarbonate (PC)
      tube to water samples at 37 degrees C, (2) effect of reactive oxygen species
      (ROS) produced by Fenton reaction on BPA recovery and thiobarbituric acid (TBA)
      value with or without generally existing environmental substances such as
      alcohol, lipids and NaCl, were investigated. Amounts of BPA leached from PC tube
      to water samples containing lipids possessing unsaturated fatty acid with high
      TBA values were significantly lower than the amount of BPA to water only, and
      addition of NaCl to lipid containing water further decreased BPA concentration.
      The result indicates that BPA could be degraded by lipoperoxides formed by auto
      oxidation of lipid, and NaCl plays an important role in BPA degradation. In the
      presence of ROS, BPA recovery was the lowest in water and addition of EtOH
      increased in both BPA recovery and TBA value, suggesting that EtOH could play a
      role as scavenger of ROS on the oxidative BPA degradation. Furthermore, the
      higher the concentration of lipid and/or NaCl, the lower the BPA recovery and TBA
      value. Physiologically and environmentally important concentrations of NaCl could
      enhance oxidative degradation of BPA in the presence of ROS.

PMID- 11827296
TI  - Application of the Microtox test and pollution indices to the study of water
      toxicity in the Albufera Natural Park (Valencia, Spain).
AB  - The toxic effects of waters collected from irrigation channels in a Mediterranean
      wetland (Albufera Natural Park, Valencia, Spain) were tested with the Microtox
      assay and compared with six pollution indices (PIs) defined from analytical
      parameters. Chemical oxygen demand (COD), biological oxygen demand (BOD),
      nutrients, heavy metals and pesticides were measured. The bioassay result
      (concentrations of the water sample (% V/V) that reduced light emission to 10%,
      20% and 50%, EC10, EC20 and EC50, respectively (ECs)) was compared with the PIs.
      This comparison has demonstrated a general agreement between ECs and PIs, except
      in the case of irrigation channels affected by herbicides used in rice farming
      (molinate and thiobencarb). No pronounced inhibition was detected in the
      bioluminescence in relation to the eutrophic parameters in the irrigation waters
      for EC50 values, indicating that this parameter does not suffice to detect
      eutrophic waters. Data derived from irrigation water pollution and bioassay were
      assembled by multivariate statistical techniques (principal component analysis).
      These components were associated with various contamination sources.

PMID- 11827297
TI  - The diagnosis and management of epilepsy.

PMID- 11827298
TI  - The validation of Developmental Screening Inventory (DSI) on Nigerian children.
AB  - In a response to the dearth of valid development assessment instruments in
      Nigeria, this study sets out to validate the Developmental Screening Inventory
      (DSI) against a performance developmental instrument, i.e. the Bayley Scales of
      Infant Development (BSID). Each member of a group of 128 healthy Nigerian
      children, obtained by selecting 16 of them from each of eight developmentally
      distinct age sub-groups (8,16 and 32 weeks and 10, 12, 18, 24 and 30 months),
      were tested on both instruments under controlled conditions. Reliability based on
      Cronbach's correlation coefficient was found to be significantly high (p < 0.01)
      at a value of +0.64, and scores of both instruments correlated significantly
      indicating satisfactory validity. Cheapness and ease of administration, as
      reported elsewhere, further enhance the suitability of DSI as an instrument for
      use in paediatric practice in Nigeria and probably in other African countries.

PMID- 11827299
TI  - Exclusive breastfeeding and infant growth studies: reference standards for head
      circumference, length and mid-arm circumference/head circumference ratio for the
      first 6 months of life.
AB  - This paper presents the development of reference standards for head circumference
      (HC), length and mid-arm circumference/head circumference (MAC/HC) ratio for the
      evaluation of exclusively breastfed infants. A total of 219 exclusively breastfed
      term appropriate-for-gestational age (AGA) infants were studied and analysed from
      1 June 1995 to 31 May 1997 at the Neonatal Follow-up Clinic, University Teaching
      Hospital, Benin City, Nigeria. Head circumference and length measurements were
      recorded for the infants at each postnatal completed month. MAC/HC ratios were
      also computed for each infant at each completed postnatal month. There was a
      progressive increase in the mean measurements at the completed months with
      increasing postnatal age and the differences between the mean measurements of
      length and head circumference at the 4th and 6th completed months were
      significant (p < 0.001). The head circumference, length and MAC/HC ratio had
      significant correlations with postnatal age. The standards represent the
      regression lines of the anthropometric measurements and MAC/HC ratio on postnatal
      age with the corresponding 95 per cent confidence limits. The standards
      identified 95 per cent (for head circumference), 93 per cent (for length) and 94
      per cent (for MAC/HC ratio) of exclusively breastfed healthy infants as having
      normal infant growth for age.

PMID- 11827300
TI  - Impact of multiple dose measles vaccination on measles transmission patterns in
      Gweru, Zimbabwe.
AB  - Multiple dose measles vaccination was applied in Gweru, Zimbabwe in 1990-1996.
      This included (a) a vaccine administered to children at 9 months of age and
      revaccination of the same children at any point between the ages of 12 and 23
      months, and (b) a single mass vaccination campaign targeted at children aged 12
      119 months (who were vaccinated irrespective of vaccination status or disease
      history) run in early 1990. This study describes the impact of this schedule on
      measles transmission patterns. Using measles disease surveillance data the study
      compared measles transmission patterns under single dose vaccination in 1983-1989
      and under multiple dose vaccination in 1990-1996. Median measles incidence rates
      were 261.0 and 19.0/100000 population in 1983-1989 and 1990-1996, respectively,
      and these were different (p = 0.002). Vaccinated cases (vaccine failures) among
      children aged 10-119 months significantly increased from 49.6 to 70.4 per cent of
      all reported cases in 1983-1989 and had a median incidence rate of 480.4/100000.
      In 1990-1996 the median incidence rate was 12.8 and these incidence rates were
      different (p = 0.002). Cases aged 60-119 months significantly increased from 14.3
      to 62.2 per cent of all reported cases in 1983-1989 and had a median incidence
      rate of 654.1/100000. In 1990-1996 the median incidence rate was 21.4 and these
      incidence rates were different (p = 0.004). It was concluded that under multiple
      dose vaccination, lower measles incidence rates occurred most likely due to
      reduction of both vaccine failures and cases aged 60-119 months.

PMID- 11827301
TI  - Increased fecal IgE among infants in a rural community of Egypt: an analysis of
      associated risk factors.
AB  - Newborns in rural Bilbeis, Egypt were followed to 1-year of age to document the
      incidence and risk factors associated with the development of fecal IgE. Factors
      associated with increased fecal IgE included infants aged 3-6 months (relative
      risk (RR) = 3.28, 95 per cent confidence intervals (CI) = 1.03-13.60, p < 0.05)
      and mother being vaccinated antenatally (RR = 2.17, CI - 1.01-4.61, p < 0.05).
      Decreased fecal IgE was observed with consumption of rice (RR = 0.37, CI = 0.12
      0.94, p < 0.05), biscuits (RR = 0.43, CI = 0.15-0.99, p < 0.05), potatoes (RR =
      0.39, CI = 0.11-0.98, p < 0.05), and fruits and vegetables (RR = 0.20, CI = 0.02
      0.80, p < 0.05). After multivariate adjustment, increased risk was observed with
      consumption of milk pudding (RR = 7.48, CI = 1.54-36.20, p < 0.05) and wet-nursed
      infants (RR = 2.77, CI = 1.17-6.54, p < 0.05). Infants who were completely
      breastfed (RR = 0.13, CI = 0.02-0.68, p < 0.05) and infants' family owning a
      television set (RR = 0.29, CI = 0.12-0.67, p < 0.05) were less likely to develop
      fecal IgE. Our findings indicate that prelacteal feeding with certain foods,
      early supplementation of breastfeeding, and sociodemographic factors are
      associated with increased fecal IgE.

PMID- 11827302
TI  - Determination of the effectiveness of inactivation of human immunodeficiency
      virus by Pretoria pasteurization.
AB  - The risk of transmission of the human immunodeficiency virus (HIV) via
      breastfeeding is between 10 and 17 per cent. In resource-poor countries most HIV
      infected women cannot afford to formula feed their infants and formula feeding is
      not desirable in areas of high infant mortality because of loss of the
      immunological benefits of breastmilk. A method has been devised by which HIV
      infected women may express and pasteurize their breastmilk in a domestic setting
      using inexpensive apparatus and a simple technique. The method, Pretoria
      Pasteurization has been shown to be reliable under a wide range of conditions and
      maintains milk between 56 degrees and 62.5 degrees C for between 12 and 15 min.
      This study was devised to determine whether Pretoria Pasteurization effectively
      inactivates HIV in human milk. Samples of expressed breastmilk were obtained from
      a group of HIV-infected lactating women and a group of HIV-negative women. The
      samples of milk from the HIV-negative women were inoculated with high titres of
      cell-associated and cell-free HIV. Each sample was divided into a control portion
      and a study portion. The study portion underwent Pretoria Pasteurization. Control
      and pasteurized samples were inoculated into lymphocyte co-culture for a period
      of 35 days. All co-cultures were sampled weekly and analysed by serological and
      molecular methods for p24 antigen, cell-free HIV RNA and integrated DNA. Viral
      RNA was detected in the milk of 80 per cent amongst the known HIV-positive women.
      The mean serum viral load in the group of HIV positive women was 50728 copies/ml
      and the mean milk viral load was 422000 copies/ml. Evidence of viral replication
      was shown in 11 of the control specimens. There was no evidence of viral
      replication in any of the study specimens which had undergone Pretoria
      Pasteurization. It was concluded that Pretoria Pasteurization effectively
      inactivates HIV in human milk.

PMID- 11827303
TI  - Assessing potential risk factors for child malnutrition in rural Kerala, India.
AB  - Studies indicate that 42-57 per cent of all child deaths in developing countries
      are due to the potentiating effects of malnutrition on infectious disease, of
      which over three-quarters can be attributed to mild-to-moderate malnutrition.
      Risk factors for underweight status in children under 3 years of age were
      assessed in Kerala, India. Mothers of 34 children weighing below -1 SD for their
      age and 59 children weighing more than 1 SD for their age, were interviewed for
      information about maternal health, child feeding patterns, and sibling gender and
      age data. Statistical analysis showed that current maternal weight (odds ratio =
      8.25, p = 0.0009), current maternal body mass index (OR = 4.55, p = 0.03), infant
      birth weight (OR = 4.87, p = 0.01) and excessive maternal vomiting in pregnancy
      (OR = 4.48, p = 0.04) were significant risk factors for current child underweight
      status. Based on this observed relationship of maternal nutritional factors with
      child weight-for-age status, further studies on interventions to address the
      health problems of adolescent girls and all women of reproductive age in Kerala
      are suggested, in addition to continuing the emphasis in current rural health and
      nutrition programs for pregnant and lactating mothers.

PMID- 11827305
TI  - Predictors of febrile seizure: a matched case-control study.
AB  - In a prospective matched case-control study carried out to determine risk factors
      of febrile seizures among children in the United Arab Emirates, 84 patients with
      febrile seizure were identified and were matched with 84 control febrile patients
      without seizure in the same age range, who attended the same hospital during the
      same period of time. Logistic regression analysis showed that the age at first
      seizure, family history of febrile seizure, duration of fever, and height of
      temperature were the only significant predictors for febrile seizures.

PMID- 11827304
TI  - Bacteremia in children: etiologic agents, focal sites, and risk factors.
AB  - A prospective study was carried out on 210 cases of children under 10 years of
      age with fever. Cases of gastroenteritis, respiratory tract infections, and
      suspected sepsis in children seen or admitted to the pediatric hospital were
      studied. Clinical and microbiological data were recorded in a questionnaire or
      obtained from patient medical records. Most of the children with septicemia (71.3
      per cent) were less than 1 year old. Focal source of bacteremia was
      gastroenteritis (40.4 per cent), pneumonia or bronchopneumonia (20 per cent),
      meningitis (7.4 per cent), and urinary tract infections (7.4 per cent). The
      predominant pathogens isolated from blood or stool specimens were gram-positive
      bacteria (53.3 per cent), mainly Streptococcus pneumoniae and coagulase-negative
      Staphylococcus spp. The gram-negative bacteria (45.6 per cent) were mainly
      Escherichia coli, Klebsiella pneumoniae, Haemophilus influenzae, Neisseria
      meningitidis, and Yersinia spp. One case of Candida albicans (1.1 per cent) was
      reported. Pasteurella pneumotropica was reported in two cases for the first time.
      The mortality rate was 4 per cent, mostly from septicemia cases. Long duration of
      hospitalization (> 10 days) and parenteral feeding were identified as risk
      factors. Resistance of the isolated pathogens to several commonly used
      antibiotics was observed. Empirical treatment with antibiotics is recommended
      only in life-threatening cases.

PMID- 11827306
TI  - Clinical characteristics of respiratory syncytial virus infection in hospitalized
      healthy infants and young children in Qatar.
AB  - To evaluate seasonal trends, clinical profile, and outcome of disease in
      previously healthy infants and young children hospitalized for respiratory
      syncytial virus (RSV) infection at Hamad Medical Corporation in the state of
      Qatar, we reviewed the records of 257 children admitted between 1 January 1996
      and 31 December 1998. RSV epidemics occurred yearly during the winter months with
      peak hospitalizations occuring between November and February. Of the 257
      admissions, 160 (62.3 per cent) were male and 97 (37.7 per cent) female. The mean
      age of all children was 5.7 months (range, 10 days to 32 months). The most common
      admitting diagnoses were bronchiolitis (59.9 per cent), pneumonia (17.5 per
      cent), bronchiolitis with pneumonia (8.9 per cent), possible sepsis (7.8 per
      cent), asthma (4.7 per cent) and apnea (1.2 per cent). A family history of asthma
      was quite common (63.8 per cent), although no statistical significant difference
      was noted in complication or length of stay. Treatment was supportive, the
      majority of the patients received oxygen therapy in 77.8 per cent of cases,
      bronchodilators in 85.4 per cent, and antibiotics therapy in 49.4 per cent. The
      median duration of hospital stay was 6 days (range, 1 to 29 days). Of the 14 (5.4
      per cent) patients requiring intensive care, four (1.6 per cent) needed
      mechanical ventilation. No deaths were reported, but subjects aged < or = 12
      months had a significantly higher oxygen requirement, intensive care unit
      admission, bronchodilators and antibiotics therapy than those > 12 months old.
      Within 1-2 years after admission with RSV infection, 63 of the 257 patients
      attended for recurrent episodes of wheezy chest. These results indicate that,
      during the season of infection, RSV is an important pathogen in infants and young
      children in the state of Qatar, highlighting the need for development of
      effective vaccines to ameliorate the impact of annual RSV epidemics in infants
      and young children.

PMID- 11827307
TI  - Comparison of results of skin prick tests, enzyme-linked immunosorbent assays and
      food challenges in children with respiratory allergy.
AB  - The present study was undertaken to investigate if enzyme-linked immunosorbent
      assays (ELISA) alone or in combination with skin tests could provide a better
      indicator of clinical food hypersensitivity in children with respiratory allergy.
      Skin prick tests (SPT) were performed on 64 children with crude antigenic food
      extracts. Oral food challenges were administered to children to confirm or rule
      out allergenicity of the food(s) incriminated, on the basis of the clinical
      history and/or a positive skin test. ELISA tests were then performed on the serum
      samples of all 64 children of study group as well as 32 children of the control
      group. SPT was found to be more sensitive as it detected a greater number of food
      challenge positive patients as compared to ELISA (92.85 vs 28.57 per cent).
      However, ELISA was found to have better specificity than SPT (88.04 vs 64.30 per
      cent). Clinically significant in our patients were 18.86 per cent of positive SPT
      and 4.81 per cent of positive ELISA. Our study shows that an ELISA value within
      the normal range is a reliable predictor of non-allergy, whereas IgE
      determination as a screening test for allergy is not reliable. Moreover, ELISA in
      itself or in combination with SPT had no advantage over SPT alone in correctly
      diagnosing food hypersensitivity.

PMID- 11827308
TI  - Changing antibiotic sensitivity in enteric fever.
AB  - Emergence of drug resistance in enteric fever is a major concern for the
      clinician. All children hospitalized with enteric fever during the period 1 March
      to 31 May 2000 were studied prospectively for their clinical presentation and
      response to therapy, and an attempt was made to compare these results with the
      results of hospitalized children with enteric fever during a similar period in
      the years 1990 and 1995. The results revealed that there was a significant change
      in the response to antibiotic therapy as evidenced by significant resistance to
      ciprofloxacin (55.5 per cent) and early evidence of emerging drug resistance to
      ceftriaxone (4.4 per cent). Although the sample size was small and had its
      limitations, the results also pointed towards the re-emergence of sensitivity to
      chloramphenicol.

PMID- 11827310
TI  - Urinary tract infection in children due to drug-resistant bacteria--a study from
      south India.

PMID- 11827309
TI  - Unusual presentation of galactosemia in a 4-month-old child.
AB  - Galactosemia is a rare inborn error of metabolism, which if detected can be
      treated effectively. Galactosemia can occur due to the deficiency of either
      galatose-1-phosphate uridyl transferase (GLUT) or galactokinase. Both these
      deficiencies have their characteristic presentation. In this case report we
      describe a 4-month-old infant who presented with clinical symptoms highly
      suggestive of GLUT deficiency but on investigation turned out to be galactokinase
      deficiency.

PMID- 11827311
TI  - Reference charts for arm, chest and head circumferences of south Iranian infants.

PMID- 11827312
TI  - Upper respiratory infection in acute pediatric care in internal conflict, Kosovo,
      1999.
AB  - Only a few reports focus on health issues among pediatric populations in internal
      conflicts including care for internally displaced persons (IDPs). This report
      examined the risk factors for pediatric upper respiratory infection (URI) during
      the internal conflict in Kosovo that presented at an acute care clinic before the
      aerial bombardment campaign by the North Atlantic Treaty Organization (NATO) in
      March 1999. The pediatric clinic was organized and managed by Kinderberg, one of
      the German humanitarian non-governmental organizations (NGOs) in the town of
      Vucitrn, 20 km north of the capital of Kosovo in mid-February 1999 at the height
      of internal conflicts and massive population migration in the area. This report
      discusses the results of a risk factor analysis for URI including overcrowding,
      malnutrition, and presence of smokers. A comparison of anthropometric
      measurements among IDPs and non-IDPs in our clinic populations was conducted to
      evaluate the state of nutrition in these two groups. There were no significant
      differences among IDPs and non-IDPs in anthropometric measurements. Smoking and
      having less than three meals per day were statistically associated with the
      increased risk of URI. Even during emergency medical interventions, prevention
      programs, such as smoking cessation and food security, may decrease URI in this
      pediatric population.

PMID- 11827313
TI  - Influence of the character of NOM on the ozonation of MIB and geosmin.
AB  - Tastes and odours (T&Os) are a major concern in drinking water as they are not
      efficiently removed by conventional water treatment. Ozonation has been effective
      for their destruction in some studies. However, the natural organic matter (NOM)
      in waters can affect the ozonation process and subsequently affect the
      destruction of T&Os. Five NOM fractions were isolated and ozonated in synthetic
      waters. The fraction containing the more highly coloured, higher molecular weight
      compounds exhibited the highest ozone (O3) demand, whereas the low aromatic
      fraction exhibited the lowest O3 demand. The character of the NOM fractions
      influenced the ozonation of MIB and geosmin. The destruction of MIB and geosmin
      was significantly higher in the fraction with the highest colour and UV/visible
      absorbance at all O3 doses. The destruction of the compounds in the other
      fractions showed the same trends, increasing MIB and geosmin destruction with
      increasing UV/visible absorbing character of the NOM. MIB was also ozonated in
      two real waters. with results showing a competing effect between NOM
      concentration and NOM character. The O3 reaction time was shown to be important
      for the destruction of both compounds.

PMID- 11827314
TI  - Prevalence of Cryptosporidium oocysts and giardia cysts in the drinking water
      supply in Japan.
AB  - A one-year monitoring of Cryptosporidium oocysts and Giardia cysts was conducted
      at a water purification plant. A total of 13 samples of 50 L river source water
      and 26 samples of 2,000 L-filtered water, treated by coagulation flocculation,
      sedimentation and rapid filtration, were tested. Prior to conducting a survey of
      a water purification plant, we developed a method for concentrating
      Cryptosporidium oocysts from a large volume of raw or filtered water using a
      hollow fiber ultrafiltration (UF) membrane, and this procedure was adapted to
      survey a water purification plant. Cryptosporidium oocysts were detected in all
      of the 13 raw water samples. The geometric mean concentration was 40 oocysts 100
      L. Giardia cysts were detected in 12 of 13 raw water samples (92%) and the
      geometric mean concentration was 17 cysts/100 L. Probability distributions of
      both Cryptosporidium oocyst and Giardia cyst concentration in raw water were
      nearly lognormal. In filtered water samples, Cryptosporidium oocysts were
      detected in 9 of the 26 samples (35%) with the geometric mean concentration of
      1.2 oocysts /1,000 L and Giardia cysts in 3 samples (12%) with 0.8 cysts/1,000 L.
      The estimated log10 removal efficiency of Cryptosporidium oocysts and Giardia
      cysts by rapid-sand filtration was 2.47 and 2.53, respectively. Empty particles
      were removed at a higher log10 than intact oocysts and cysts. The efficiency of
      particle removal in the rapid sand filtration process tends to be reduced under
      cold-water conditions. Close management is necessary in the winter when the water
      temperature is low.

PMID- 11827315
TI  - Examination of three theories for mechanisms of cation-induced bioflocculation.
AB  - Research from different studies has been used to support three different theories
      pertaining to the role of cations in bioflocculation. These theories are the
      alginate theory. Derjaguin, Landau, Verwey, and Overbeek (DLVO) theory, and
      divalent cation bridging (DCB) theory. The objectives of this research were to
      examine the role of cations in bioflocculation to determine which theory, if any,
      best describes cation induced bioflocculation. Experiments were performed using
      laboratory scale activated sludge systems with bactopeptone as a feed. The feed
      was supplemented with either calcium, magnesium, or sodium at increasing
      concentrations. Floc properties were analyzed in each reactor during steady state
      periods. The addition of calcium or magnesium to the feed individually resulted
      in improvements in SVI, CST, SRF, cake solids and floc strength and each of these
      divalent cations produced similar results. The addition of sodium to the feed
      resulted in a deterioration in floc properties relative to a control reactor.
      Analysis of these results suggest that the DCB theory best explains the role of
      cations. The discrepancies between different studies were examined and are
      thought to be a result of different experimental procedures in different studies
      and in particular the use of short-term batch tests versus continuous flow
      reactor studies. In addition, the implications of DCB theory suggests that
      activated sludge systems should attempt to lower the ratio of monovalent to
      divalent cations to improve floc properties and treatment performance.

PMID- 11827316
TI  - Network strength and dewaterability of flocculated activated sludge.
AB  - Works in literature proposed the use of the rheological properties of wastewater
      sludges as an index for conditioner assessment and control. We demonstrated in
      this work, on the contrary, that one could not justify the consistency of the
      commonly used rheological characteristics of the sewage sludge samples taken from
      the same site but at different dates. A physically relevant index was proposed
      instead for describing the total network strength, which was hypothesized to
      correlate the dewatering efficiency of flocculated sludge. Based on this index,
      the network of a sludge was demonstrated to be largely destroyed after shearing,
      while the relaxation in an unbound environment or mild pouring over action could
      partially reinstall the structure. Moreover, a uniform shear rate field could
      produce network of greater strength when compared with that conditioned in a
      stirred tank.

PMID- 11827317
TI  - Adsorption of p-chlorophenol by biofilm components.
AB  - Through batch equilibrium experiments under the conditions of temperature 25
      degrees C, pH values of 2.7, 5.3 and 6.1, the p-chlorophenol (4-cp) adsorption to
      biofilm components was investigated in this study. The contributions of biofilm
      components to 4-cp adsorption were discussed by comparing four adsorption
      systems, i.e. 4-cp adsorbed by model suspended particulate matter (kaolin) with
      biofilm coating, bacteria, bacterial exopolysaccharide (EPS) and kaolin,
      respectively. Langmuir and Freundlich isotherm equations were used to evaluate
      the experiment data. All the four adsorptions fitted for the two equations.
      Equilibrium isotherms were obtained for 4-cp adsorption on different adsorbents.
      The kinetic characteristics of 4-cp adsorption by biofilm components and the
      effect of pH on the kinetic process were investigated. The time to reach the
      highest adsorption amount and near equilibrium state in the four systems was
      different. The 4-cp adsorption by kaolin with biofilm coating reached near
      equilibrium at 60 min at pH 6.1. The 4-cp adsorption by EPS and kaolin reached
      near equilibrium at 150 and 180 min, respectively. But the 4-cp adsorption by
      bacteria showed no evident near equilibrium during 3 h in the experiment. The
      impact of pH value on the adsorption was also examined. The adsorption amount
      slightly increased with increasing pH from 2.7 to 6.1 for the adsorption systems
      of bacterial EPS and kaolin, but it slightly decreased in the systems of kaolin
      with biofilm coating and bacteria.

PMID- 11827318
TI  - Interactive effects of the electron acceptor sulphate and o-cresol on the
      methanogenic degradation of hexanoate.
AB  - A three-stage continuous culture system was used to segregate the component
      microbial groups of a methanogenic hexanoate-degrading association enriched from
      anaerobic refuse. The inhibitory effects of o-cresol concentrations (2-20 mM) on
      the fermentative, acetogenic, sulphate-reducing and methanogenic bacteria were
      then assessed in the presence of either 1.4 or 3.5 mM sulphate in the influent
      medium. The sulphate-reducing bacteria (SRB) in the 1.4 mM sulphate-supplemented
      systems were the most sensitive to o-cresol, with 29.3 and 56.6% inhibition on
      supplementation with 4 and 6 mM o-cresol, respectively. With 3.5mM
      supplementation, inhibition was 4.5 and 19.4%, respectively. Methanogenesis was
      not inhibited by concentrations < 10 mM o-cresol, and complete inhibition was
      recorded only at concentrations > or = 10 mM. Both fermentation and acetogenesis
      were affected by inhibition of the electron sinks. The increase in influent
      sulphate concentration promoted electron flow to sulphidogenesis, as predicted on
      thermodynamic criteria, but did not affect the relative sensitivity of the
      different physiological groups.

PMID- 11827319
TI  - Plant carbohydrate limitation on nitrate reduction in wetland microcosms.
AB  - Although nitrate limitation in most natural wetlands results in pseudo-first
      order reductions, large site-to-site variations in apparent denitrification rates
      cannot be easily explained by water quality (e.g., pH, Temp, DOC) or plant
      productivity. Our microcosm results show increasing nitrate removal efficiencies
      at higher ratios of total applied plant carbon to nitrate reduced, suggesting
      that denitrification rates may be limited by the rates of supply of both electron
      donor or acceptor, described by an applied carbon to nitrate (C(App): N(Red))
      ratio. However, the observed first-order rate constants varied more strongly (r2
      = 0.77, p <0.0001) with the acid-soluble carbohydrates to nitrate (CH2O(App):
      N(Red)) ratio than the total C(App): N(Red) ratio. Although observed rate
      constants for bulrush (Scirpus sp.) were significantly lower (0.01 <p<0.06) than
      for other plant sources (Hydrocotyle sp., Lemna sp., Typha sp.), there were no
      significant differences in the plant-specific rate constants when compared at the
      same CH2O(App): N(Red) ratio. In full-scale wetlands, this suggests that either
      high plant productivity or low NO3- loading (high CH2O(App): N(Red)) may
      contribute to a high effective denitrification rate. In contrast, low
      productivity or a high NO3- loading (low CH2O(App): N(Red)) would promote a lower
      denitrification rate. This co-limitation between plant carbon and nitrate may
      confound first-order rate comparisons in full scale denitrification wetlands
      since highly N-loaded systems may become carbon limited, requiring higher order
      reaction kinetics to better describe performance variations. In addition to
      hydraulic residence time. temperature and nitrate removal data, extending these
      results to compare large wetlands will require estimation of the CH2O(App):
      N(Red) ratio from an inventory of plant species, productivity estimates and
      carbon quality.

PMID- 11827320
TI  - Effect of solution physico-chemistry on the charge property of nanofiltration
      membranes.
AB  - Electrokinetic phenomenon is an important factor in pressure-driven membrane
      water filtration process. Zeta potential is a measurable and reliable parameter
      to characterize the charge property of membranes. This study investigated the
      effects of solution physico-chemistry on the zeta potential of nanofiltration
      membranes. A comprehensive semi-empirical mathematical model based on the Poisson
      Boltzmann equation, Membrane Surface Charge model, was established. The
      correlations between the zeta potential, surface charge density and solution
      chemistry were well delineated by this new model. The empirical coefficients in
      the model are dependent on neither solution pH nor the ionic strength. They only
      reflect the characteristics of the electrokinetic property of the membrane-
      solution interface. The point of zero charge (PZC) can be calculated by
      combination of those empirical coefficients. The Membrane Surface Charge model
      also provides more information on understanding the charge interaction involved
      in membrane filtration system. The effects of potential determining ions,
      indifferent ions and specific adsorption of substances onto the membrane could be
      revealed by analyzing the coefficients of the model.

PMID- 11827321
TI  - Comparison of adsorption equilibrium and kinetics of four chlorinated organics
      from water onto GAC.
AB  - This study deals with the adsorption of four chlorinated pollutants onto GAC (F
      400); two pesticides (lindane and alachlor) and two PCB congeners: 2-PCB (MPCB)
      and 2,2',5,5'-PCB (TPCB). Equilibrium and kinetic parameters have been obtained
      for the adsorption of alachlor and each PCB. whereas the kinetic results for
      lindane presented elsewhere (Proc. First World Water Congr. Int. Water Assoc.,
      Texts of Posters, CD-ROM, AGHTM, Paris, 2000) are reanalyzed in this work. A
      model assuming a bidisperse structure (macro- and micropores). each region having
      a different adsorption isotherm, is used to study the adsorption kinetics in a
      batch system in the period dominated by macropore diffusion. Both the saturation
      capacity and the rate of internal transport of TPCB are much lower than those of
      the other solutes. This difference is attributed to a chemisorption mechanism for
      this compound, which is favored by its very low solubility.

PMID- 11827322
TI  - Decolorization of wastewater of a Baker's yeast plant by membrane processes.
AB  - The aim of this study is to develop a membrane-based treatment scheme to remove
      colorants from the effluent of a baker's yeast plant. For this purpose
      microfiltration (MF), ultrafiltration (UF) and nanofiltraton (NF) membranes with
      differing molecular weight cut-offs (MWCOs) were tested. To evaluate the
      effectiveness of membrane processes in treating the waste stream, optical density
      (OD), COD, color measurements together with permeation fluxes were used. Effects
      of pretreatment methods (coagulation and coarse filtration) and feed composition
      on OD, color, COD were studied. In addition, gel filtration analysis was employed
      to characterize feed and permeate streams in terms of MW distribution of organics
      that are present. Maximum rejections obtained were 94%, 89% and 72% for OD, color
      and COD, respectively, when 0.8 microm microfiltration membrane and 400 Da NF
      membrane were used in series. It was also observed that addition of intermediate
      UF steps did not increase overall rejections and final permeate flux of NF
      membrane. Based on these observations, an efficient scheme was offered.

PMID- 11827323
TI  - Evaluation of a rapid physical-chemical method for the determination of extant
      soluble COD.
AB  - Characterization of total chemical oxygen demand (COD) in wastewater is critical
      for accurate modeling of constituent biotransformation steps. We evaluated the
      accuracy and precision of a commonly used soluble COD determination technique
      (coagulation using ZnSO4 at pH 10.5) in relation to three other physical-chemical
      separation techniques: destabilization with a non-hydrolyzing trivalent cation
      (LaCl3), sequential filtration, and ultracentrifugation. Samples of deionized
      water and domestic wastewater were spiked with aliquots of synthetic soluble COD
      and recoveries using the different separation methods were compared. Although
      mechanisms of coagulation using LaCl3 and ZnSO4 are different, the mean COD
      recoveries using these methods were in close agreement. Further, sorption of
      soluble COD onto zinc hydroxide precipitate flocs appeared to be negligible. The
      two coagulation methods yielded statistically different (p = 0.05) soluble COD
      values when applied to nine independent wastewater samples (obtained on nine
      different days). but the difference was less than 10%. The COD quantified by the
      coagulation techniques corresponded most closely with the < 1,000 Da molecular
      weight fraction defined as "truly soluble COD". Centrifugation of wastewater
      samples amended with mercuric chloride (HgCl2) at 10 mg/L overestimated the
      soluble COD concentration. Our results confirm that coagulation using either
      ZnSO4 or LaCI3 is appropriate for the rapid determination of soluble COD fraction
      in wastewater matrices.

PMID- 11827325
TI  - A method for treating wastewater containing formaldehyde.
AB  - Many industrial activities utilise formaldehyde as a key chemical in organic
      synthesis including: synthesis of special chemicals such as pentaerythritol and
      ethylene glycol, synthetic resins, paper products, medicinal products and drugs
      and others, too numerous to mention. Therefore, effluents arising from these
      applications may contain significant amounts of formaldehyde. In a biodegradation
      experiments of a wastewater sample containing formaldehyde ranging from 31.5 to
      125 mg/l, residual formalin (a solution of formaldehyde gas in water) ranging
      from 40% to 85%, respectively, was found at the end of the run (16 d) showing the
      inhibition effect of formalin which increased with the increase in formalin
      concentration. The biodegradation of formalin decreased significantly at
      concentrations higher than 300 mg/l. A method to convert formaldehyde to an
      easily biodegradable substance is herein described. In the commercial manufacture
      of resins from phenol and formalin the reaction is never completely quantitative.
      As a result during the dehydration stage phenol and formalin are distilled from
      the wastewater. Phenol is toxic to several biochemical reactions. However,
      biological transformation of phenol to a non-toxic entity is possible through
      specialized microbes. Transformation of phenol is inhibited by the presence of
      formaldehyde. Biotransformation of phenol in a wastewater containing high
      concentrations of formaldehyde started shortly after treating the wastewater with
      calculated amounts of sodium sulphite. Sodium sulphite is believed to react with
      formaldehyde forming sodium formaldehyde bisulphite, which is not only non-toxic
      to microorganisms but also a biodegradable substance. From the DO measurements
      before and after the addition of sodium sulphite, the authors noticed that the
      dissolved oxygen in a wastewater containing formaldehyde is not affected by the
      addition of the calculated amount of sodium sulphite, which is just enough to
      consume the measured amount of formaldehyde in that wastewater.

PMID- 11827324
TI  - Removal of arsenic from groundwater using low cost ferruginous manganese ore.
AB  - A low cost ferruginous manganese ore (FMO) has been studied for the removal of
      arsenic from groundwater. The major mineral phases present in the FMO are
      pyrolusite and goethite. The studied FMO can adsorb both AS(III) and As(V)
      without any pre-treatment, adsorption of As(III) being stronger than that of
      As(V). Both As(II) and As(V) are adsorbed by the FMO in the pH range of 2-8. Once
      adsorbed, arsenic does not get desorbed even on varying the pH in the range of 2
      8. Presence of bivalent cations, namely, Ni2+, Co2+ Mg2+ enhances the adsorption
      capability of the FMO. The FMO has been successfully used for the removal of
      arsenic from six real groundwater samples containing arsenic in the range of 0.04
      0.18 ppm. Arsenic removals are almost 100% in all the cases. The cost of the FMO
      is about 50-56 US$ per metric tonne.

PMID- 11827326
TI  - Stability of the bacterial communities supported by a seven-stage biological
      process treating pharmaceutical wastewater as revealed by PCR-DGGE.
AB  - The stabilities of the bacterial community structures supported by seven full
      scale biological reactors treating pharmaceutical wastewater were investigated by
      denaturing gradient gel electrophoresis (DGGE) of polymerase chain reaction (PCR)
      amplified 16S rRNA gene fragments. Effluent quality from this treatment process
      was consistently high with respect to BOD5 (<30 mgl(-1)), soluble COD (<500 mgl(
      1)), and total ammonia (< 5 mgl(-1) as N) concentrations. Long-term community
      structure stability was studied by comparing the similarity of PCR-DGGE
      fingerprints from samples collected 87 days apart between which the influent
      wastewater characteristics were relatively stable. The Dice index (Cs) of
      similarity was moderately high for the first four reactors (Cs = 0.61-0.77) and
      very high for the last three reactors (Cs = 0.89-0.91). Short-term community
      structure stability was studied by comparing PCR-DGGE fingerprints from samples
      collected 15 days apart between which the influent wastewater characteristics
      changed significantly, while the effluent quality remained consistently high. The
      bacterial community composition of each of the seven bioreactors showed a
      moderate community shift (Cs = 0.70-0.76). Short-term variability in influent
      wastewater composition, therefore, affected a greater community shift than did
      long-term operation treating a wastewater of relatively consistent composition.
      These results indicate that functionally stable wastewater treatment bioreactors
      have stable microbial community structures under normal operating conditions but
      are able to adapt in response to perturbations to sustain high effluent quality.

PMID- 11827327
TI  - Adsorption of nitrophenol onto activated carbon: isotherms and breakthrough
      curves.
AB  - The adsorption isotherm of p-nitrophenol onto granular activated carbon in 25
      degrees C aqueous solution was experimentally determined by batch tests. Both the
      Freundlich and the Redlich-Peterson models were found to fit the adsorption
      isotherm data well. A series of column tests were performed to determine the
      breakthrough curves with varying bed depths (3-6 cm) and water flow rates (21.6
      86.4 cm3/h). Explicit equations for the breakthrough curves of the fixed-bed
      adsorption processes with the Langmuir and the Freundlich adsorption isotherms
      were developed by the constant-pattern wave approach using a constant driving
      force model in the liquid phase. The results show that the half breakthrough time
      increases proportionally with increasing bed depth but decreases inverse
      proportionally with increasing water flow rate. The constant-pattern wave
      approach using the Freundlich isotherm model fits the experimental breakthrough
      curves quite satisfactorily. A correlation was proposed to predict the volumetric
      mass-transfer coefficient in the liquid phase successfully. The effects of
      solution temperature and pH on the adsorption isotherm were also studied and the
      Toth model was found to fit the isotherm data well at varying solution
      temperatures and pHs.

PMID- 11827328
TI  - Feasibility of using a chlorination step to reduce excess sludge in activated
      sludge process.
AB  - The ultimate disposal of excess sludge generated from activated sludge processes
      has been one of the most challenging problems for wastewater treatment utilities.
      Previous work has shown that excess sludge can be minimized successfully by using
      sludge ozonation to dissolve it into substrates to be oxidized in the aeration
      tank. However, this approach is a costly option. Therefore, as an alternative
      solution, we propose to use chlorination to replace ozonation in excess sludge
      minimization in the light of operational cost. To investigate the feasibility of
      this low cost approach, this paper mainly focuses on the effect of chlorination
      on sludge reduction rate, formation of trihalomethanes, sludge settleability, and
      effluent quality. Two identical activated sludge membrane bioreactors were
      continuously operated with synthetic wastewater under the same operation
      conditions for several months. During this period, one pilot unit was used as the
      reference system without chlorination of excess sludge, while another served as a
      testing unit, where excess sludge was taken out for conducting chlorination at a
      dose of 133mg/g MLSS every day and the chlorinated liquor was then returned to
      the aeration tank. The sludge production rate and the water quality of both the
      units were analyzed daily. It was observed that the sludge production could
      readily be reduced by 65% once the chlorination treatment was involved. However,
      the chlorination treatment also resulted in poor sludge settleability as well as
      significant increase of soluble chemical oxygen demand in the effluent, which
      creates potential difficulties in the operation of a conventional treatment plant
      with gravity clarifiers. However, it has been demonstrated that by integrating
      the immersed membrane into the activated sludge process these difficulties can be
      overcome effectively.

PMID- 11827329
TI  - Simultaneous adsorption and biodegradation processes in sequencing batch reactor
      (SBR) for treating copper and cadmium-containing wastewater.
AB  - The application of simultaneous adsorption and biodegradation processes in the
      same reactor is known to be effective in the removal of both biodegradable and
      non-biodegradable contaminants in various kinds of wastewater. The objective of
      this study is to evaluate the efficacy of the two processes under sequencing
      batch reactor (SBR) operation in treating copper and cadmium-containing synthetic
      wastewater with powdered activated carbon (PAC) as the adsorbent. The SBR systems
      were operated with FILL, REACT, SETTLE, DRAW and IDLE periods in the ratio of
      0.5: 3.5: 1.0: 0.75 :0.25 for a cycle time of 6 h. In the presence of 10 mg/L
      Cu(II) and 30 mg/L Cd(II), respectively, the average COD removal efficiencies
      were above 85% with the PAC dosage in the influent solution at 143 mg/L compared
      to around 60% without PAC addition. Copper(II) was found to exert a more
      pronounced inhibitory effect on the bioactivity of the microorganisms compared to
      Cd(II). It was observed that the combined presence of Cu(II) and Cd(II) did not
      exert synergistic effects on the microorganisms. Kinetic study conducted for the
      REACT period showed that the addition of PAC had minimized the inhibitory effect
      of the heavy metals on the bioactivity of microorganisms.

PMID- 11827330
TI  - Evolution of size distribution and transfer of mineral particles between flocs in
      activated sludges: an insight into floc exchange dynamics.
AB  - The aggregation behavior of activated sludge flocs was investigated by monitoring
      the size distribution of flocs and transfer of mineral particles between flocs,
      under various conditions of agitation and dilution. The results showed that (i)
      the shape of the floc size distribution can be fitted with a gamma function, (ii)
      a steady-state mean floc size is reached for a given stirring rate, (iii) this
      stable floc size is shifted towards floc growth as sludge concentration is
      increased, (iv) under cycled-shear conditions, microbial aggregates break up and
      re-form in an almost reversible manner, (v) blending of raw sludge and sludge
      spiked with Aquatal mineral particles results in particle exchange between flocs
      and (vi) the detailed study of exchange kinetics indicates that some flocs do not
      participate to the aggregation dynamics. These experimental results suggest that
      the activated sludge floc size is governed by a flocculation/deflocculation
      balance, implying an exchange of floc constituents between microbial aggregates.

PMID- 11827331
TI  - The phosphorus content of fluvial sediment in rural and industrialized river
      basins.
AB  - The phosphorus content of fluvial sediment (suspended sediment and the < 63
      microm fraction of floodplain and channel bed sediment) has been examined in
      contrasting rural (moorland and agricultural) and industrialized catchments in
      Yorkshire, UK. The River Swale drains a rural catchment with no major urban and
      industrial areas, and the total phosphorus (TP) content of fluvial sediment is
      generally within the range 500-1,500 microg g(-1). There is little evidence of
      any major downstream increase in TP content. In contrast, fluvial sediment from
      the industrialized catchments of the Rivers Aire and Calder exhibits both higher
      levels of TP content and marked downstream increases, with values of TP content
      ranging from < 2,000 microg g(-1) in headwater areas upstream of the main urban
      and industrial areas, to values > 7,000 microg g(-1) at downstream sites. These
      elevated levels reflect P inputs from point sources, such as sewage treatment
      works (STWs) and combined sewer overflows. The influence of STWs is further
      demonstrated by the downstream increase in the inorganic P/organic P ratio from <
      2 in the headwaters to > 4 in the lower reaches. Comparison of the P content of
      suspended sediment with that of the <63 microm fraction of potential source
      materials suggests that topsoil from upland moorland/pasture and from cultivated
      areas, and channel bank material are likely to be the main sources of particulate
      P (PP) in the River Swale and in the headwaters of the Rivers Aire and Calder. In
      the middle and lower reaches of the Rivers Aire and Calder, inputs associated
      with urban and industrial land uses, such as STWs, industrial effluents and
      street dust, are likely to represent the dominant sources of PP. During high flow
      events, such urban inputs may be diluted by inputs from moorland and agricultural
      land in the headwaters. Consequently, for all three rivers, there are inverse
      relationships between the TP content of suspended sediment and both discharge and
      suspended sediment concentration, reflecting changes in sediment and P sources
      during high flow events. Spatial variations in the P contents of the < 63 microm
      fraction of overbank floodplain deposits and channel bed sediment evidence a
      similar pattern as those for suspended sediment, with relatively low levels of TP
      in the River Swale and elevated levels in the middle and downstream reaches of
      the Rivers Aire and Calder. The PP concentrations associated with floodplain and
      channel bed sediment are, however, lower than equivalent values for suspended
      sediment, and this primarily reflects the differences in the particle size
      composition between the three types of sediments. Rates of floodplain deposition
      and the amounts of fine-grained sediment stored in the river channels are
      relatively high, and suggest that such environments may represent important sinks
      for PP. Based on the sediment samples collected from the study basins, a simple
      four-fold classification which relates the TP content of suspended sediment to
      upstream land use has been established. Both the range and the absolute values of
      TP content tend to increase with an increase in the level of urbanization and
      industrialization.

PMID- 11827332
TI  - Impact on the water column biogeochemistry of a Mediterranean mussel and fish
      farm.
AB  - We investigated and compared the impact of organic loads due to the biodeposition
      of mussel and fish farms on the water column of a coastal area of the Tyrrhenian
      Sea (Western Mediterranean). Physico-chemical data (including oxygen, nutrients.
      DOC and particulate organic matter), microbial variables (picoplankton and
      picophytoplankton density and biomass) and phytoplankton biomass (as chlorophyll
      a) were determined on a monthly basis from March 1997 to February 1998. The
      results of this study indicate that both fish farm and mussel culture did not
      alter significantly dissolved inorganic phosphorus and chlorophyll-a values,
      while inorganic nitrogen concentrations were higher in mussel farm area. However,
      waters overlying the fish farm presented significantly higher DOC concentrations.
      In contrast, no significant differences were observed comparing particulate
      matter concentrations. The increased DOC concentrations determined a response of
      the heterotrophic fraction of picoplankton, while picophytoplankton, likewise
      phytoplankton. did not display differences among fish or mussel farms and control
      site. From the analysis of the different microbial components, it is possible to
      conclude that the impact of fish farms is evident only for the heterotrophic
      components. The comparative analysis of the mussel biodeposition and fish-farm
      impact revealed that mussel farms induced a considerably lower disturbance,
      apparently limited to an increased density and biomass of microbial assemblages
      beneath the mussel cultures.

PMID- 11827334
TI  - Transport and sources of metal contaminants over the course of tidal cycle in the
      turbidity maximum zone of the Hudson River estuary.
AB  - Transport and source of metal contaminants (Ag, Cd, Cu, Pb and Zn) in the
      turbidity maximum zone of the Hudson River estuary were studied over the course
      of a tidal cycle in November 1994 and August 1995. This study showed that the
      metal/Fe ratios in suspended particles varied more widely than those in the local
      sediments, implying that sources of metal contaminants to the water column are
      not only from local sediment resuspension but also from lateral advection.
      Although the metal/Fe ratios oscillate with time at the anchor stations, a
      general increasing trend with salinity was found over the course of a tidal
      cycle, suggesting that the lower estuary could be a source of metal contaminants
      to the upper estuary regions. These results support that sediment resuspension
      and lateral advection are important factors responsible for transporting the
      lower estuary contaminants up river and redistributing metal contaminants in the
      estuary.

PMID- 11827333
TI  - Determination of the bacterial processes which are sources of nitrous oxide
      production in marine samples.
AB  - Partial denitrification and the initial step of nitrification are the main
      biological processes which produce nitrous oxide. In order to determine the
      contribution that these processes have in nitrous oxide production, the
      efficiency of different inhibitors on nitrifying activity has been tested, and
      the effect on denitrifying activity has been investigated, using culture strains
      and natural marine samples. A good nitrification inhibitor should not affect
      denitrification. A low partial pressure of C2H2 provided the best conditions,
      inhibiting 75%, Nitrosococcus oceanus (culture sample) and 100% (natural sample)
      of the nitrifying activity and having only a small inhibitory effect (12%) on
      denitrifying activity. These conditions have been applied on samples from the
      dilution plume of the Rhjne River, an area characterized as a source of nitrous
      oxide. Using these inhibitors, it has been shown that in this area, incomplete
      denitrification is the main process producing nitrous oxide in the surface layers
      at the mouth of the river and in the bottom nepheloid layer, whereas in the
      marine surface layer the dominant process is nitrification.

PMID- 11827335
TI  - Laboratory study of ballasted flocculation.
AB  - Ballasted flocculation is applied successfully in the water treatment industry,
      but the concept has not yet been subject to extended experimental studies. The
      use of a microsand and a polymer together to increase the weight of the flocs and
      the rate at which they settle is radically changing the coagulation flocculation
      settling methodology. The objective of this research is to study ballasted
      flocculation in the laboratory by means of a modified jar-test procedure. The
      first tests, conducted using a statistical approach, enabled us to identify those
      parameters that have a significant influence on the quality of settled water. The
      principal treatment parameters considered in this study were the chemical dosage,
      the contact times in the different basins, the pH of coagulation and the dosage
      of microsand. The parameters used to evaluate the quality of the settled water,
      and hence treatment performances, were turbidity, UV absorbance, TOC and membrane
      filterability. The results showed that the coagulant dosage and the coagulation
      pH have a preponderant effect on the variability of the quality of the settled
      water. By contrast, filterability as measured by the laboratory filter tests, was
      found to be more sensitive to coagulant and microsand dosages. It was dependent
      on the ratio of microsand to polymer dosage, and improved when this ratio
      increased.

PMID- 11827336
TI  - Mechanisms of scale formation and carbon dioxide partial pressure influence. Part
      I. Elaboration of an experimental method and a scaling model.
AB  - Scale formation in industrial or domestic installations is still an important
      economic problem. The existence of a metastable domain for calcium carbonate
      supersaturated solutions and its breakdown are observed under conditions rarely
      well defined. In most cases it is the pH rise caused by the carbon dioxide loss
      that involves calcium carbonate precipitation. Before studying this problem, we
      suggest in this first part, a new model for the evolution of the calcocarbonic
      system that takes into account the hydrated forms of CaCO3: CaCO3 amorphous,
      CaCO3 x 6H2O (ikaite) and CaCO3 x H2O (monohydrate). According to this model, the
      precipitation of any one of these hydrated forms could be responsible for the
      breakdown of the metastable state. After this first step, the solids evolve into
      dehydrated forms. At first, the metastable domain spread of the calcium carbonate
      supersaturated solutions was studied by the elaboration of computer programs in
      which the formation of CaCO3(0)(aq) ion pairs was taken into account. These ion
      pairs are supposed to evolve through dehydration to form the various calcium
      carbonate solid form precursors. This thermodynamic study was then compared to
      the experimental methods of the critical pH. Here the pH rise was caused by
      adding sodium hydroxide under different conditions for sodium hydroxide addition
      speed, agitation mode and ageing of solutions. For the highest speed of sodium
      hydroxide addition, the CaCO3 ionic product reached the value of the amorphous
      calcium carbonate solubility product, and the reaction of the amorphous calcium
      carbonate precipitation was of the homogenous type. Decreasing the reagent's
      addition speed caused an extension of the titration time. Then, the breakdown of
      the metastable state was obtained with the CaCO3 x H2O heterogeneous
      precipitation. This clearly illustrates the probable ageing of the precursors of
      the solid states that are considered in this model.

PMID- 11827337
TI  - Mechanisms of scale formation and carbon dioxide partial pressure influence. Part
      II. Application in the study of mineral waters of reference.
AB  - In the first part, we have designed a new model of evolution for the calco
      carbonic system which includes the hydrated forms of CaCO3: CaCO3 amorphous,
      CaCO3 x 6H2O (ikaite) and CaCO3 x H2O (monohydrate) (J. Eur. Hydr. 30 (1999) 47).
      According to this model, it is the precipitation of one or other of these
      hydrated forms which could be responsible for the breakdown of the metastable
      state. After this first step, the precipitates evolve to dehydrated solid forms.
      Through the elaboration of computer programs in which the CaCO3(0) (aq) ion pair
      formation was considered, this model was compared to experimental data obtained
      by the critical pH method applied to synthetic solutions. In the present article,
      the same method was applied for four French mineral waters, at 25 degrees C under
      study. Three samples formed a precipitation during the sodium hydroxide addition.
      For these three cases, this precipitation began for the CaCO3 H2O saturation. The
      added volume of sodium hydroxide was more than what was required for neutralizing
      free CO2 initially in solution. These results indicate that during a spontaneous
      scaling phenomenon, the pH rises at the same time by loss of the initial free CO2
      and of the one produced by the hydrogen carbonate ions decomposition. Then we
      calculated, at various temperatures for the three studied scaling waters: CO2
      partial pressures and loss of total carbon corresponding to the solubility
      products of CaCO3 hydrated forms. The results show that the partial pressure
      monitoring of the carbon dioxide is important in managing the behavior of scaling
      waters.

PMID- 11827338
TI  - Luxury uptake of phosphorus by sediment bacteria.
AB  - This note reports the results of experiments aimed at confirming the luxury
      uptake of phosphorus (P) by sediment bacteria as polyphosphate (Poly-P). Aerobic
      suspensions of sediments from two different sites were spiked with 1 mg P/L as
      orthophosphate and augmented with acetate (a fermentation product) or glucose.
      The orthophosphate was rapidly taken up over a period of a few hours. When these
      aerobic uptake experiments were made anaerobic and additional organic carbon
      added, only the acetate-amended sediment released a significant amount of the
      added phosphorus. It was hypothesised that during the aerobic stage, and with the
      addition of acetate, some of the phosphorus was accumulated as Poly-P by sediment
      microorganisms, which was released during the subsequent anaerobic stage
      (provided acetate was still present). Two lines of evidence--transmission
      electron microscope analysis of sediment bacteria and 31P-NMR analysis of
      sediment extracts--are presented to support the hypothesis that a portion of the
      phosphorus taken up during the aerobic experiments was stored as Poly-P.

PMID- 11827339
TI  - Gorgonians mass mortality during the 1999 late summer in French Mediterranean
      coastal waters: the bacterial hypothesis.
AB  - Mass mortality by tissue necrosis of several species of gorgons was observed
      during the 1999 late summer on the Liguro-Provencal Mediterranean coasts. We have
      investigated the occurrence of vibrios on necrosis affected gorgonians
      Paramuricea clauata and Eunicella cavolinii, and their ability to induce tissue
      necrosis. Among the 11 strains tested, only 5, belonging to species Vibrio
      splendidus, V. pelagius and V. campbellii, were able to induce tissue necrosis in
      a few days. Temperature experiments carried out at 11 degrees C, 18 degrees C and
      23 degrees C showed that necrotic disease may occur only at the higher
      temperature tested. Statistical analysis suggested that, for these thermical
      conditions, marine Vibrio strains can significantly speed up the necrotic crisis.

PMID- 11827340
TI  - Nitrate flux from aquifer storage in excess of baseflow contribution during a
      rain event.
AB  - Nitrate flux from a bedrock aquifer due to a storm was calculated by hydrograph
      separation. The hydrograph generated by a 20-mm rain in Cedar River of Iowa was
      separated into the following three components: the constant baseflow, the
      rainwater, and the water released from aquifer in excess of baseflow. The
      separation was conducted by using oxygen isotopes, dissolved nitrate, and stream
      discharge. The peak discharge was 33h long. During this period, the water
      released from the aquifer storage in excess of baseflow was 36% of the total
      discharge. The rainwater and the pre-storm baseflow equivalents were 17% and 47%,
      respectively. The nitrate concentrations in the instantaneous discharge ranged
      between 8.6 and 10.0 mg/L. The average concentrations in the rainwater and the
      baseflow were 3.7 and 9.8 mg/L, respectively. A total of 3.6 x 10(5) mol of
      nitrate was transported by the stream during the 33 h of peak discharge.
      Approximately 35% (1.3 x 10(5) mol) of this mass was derived from the aquifer
      storage in excess of baseflow contribution. The rainwater and the constant
      baseflow equivalentswere 7% (2.6 x 10(4) mol) and 58% (2.1 x 10(5) mol),
      respectively. The release of a significant amount of nitrate from the aquifer
      suggests that the local geology is favorable for vertical recharge of rainwater
      which causes an increased fluid pressure within the aquifer forcing ground water
      to discharge laterally into the stream. Such observation also implies that the
      aquifer is effectively flushed out during storms, thus restricting long term
      build-up of nitrate from agricultural sources.

PMID- 11827341
TI  - Hydrogen peroxide (H2O2) as a source of dissolved oxygen in COD-degradation
      respirometric experiments.
AB  - Two different re-oxygenation techniques (aeration and hydrogen peroxide addition)
      were compared in respirometric experiments. As similar results were obtained in
      both cases, it was concluded that the addition of hydrogen peroxide does not
      modify the oxygen uptake rate of the biomass, under either endogenous or feeding
      conditions. It was hypothesized that under those experimental conditions
      (inhibition of nitrification with ATU), hydrogen peroxide alters neither the
      biomass metabolism nor the biodegradability of the tested substrates. The oxygen
      uptake rates obtained with the aeration system were often more scattered due to
      the adhesion of fine bubbles after the switch off of the aeration. Moreover, the
      transfer rate of oxygen to the solution is faster in the case of hydrogen
      peroxide addition.

PMID- 11827342
TI  - A modified ceramic sampler and lysimeter design for improved monitoring of soil
      leachates.
AB  - This paper describes the design and use of modified solution samplers and non
      weighing lysimeters in a field experiment examining the response of a turf-soil
      system to landfill leachate irrigation over a 2-year period. The two designs were
      shown to offer significant performance advantages, were cost effective and
      overcame many of the reported problems commonly associated with each technique.
      The quantities of leached chloride detected in the 20%, 50% and undiluted
      leachate irrigated plots by the modified solution samplers (1,677, 4,319 and
      8,021 kg ha(-1), respectively) and microlysimeters (1,759, 4,512 and 8,160 kg ha(
      1), respectively) were significantly higher than the conventional sampler design
      (1,407, 3,767 and 7,052 kg ha(-1), respectively). Additionally, the
      microlysimeter design functioned reliably throughout the experiment, achieving
      solution flow rates analogous to the unconfined plots. Therefore, it was
      concluded that both the designs appear to be suitable for monitoring changes in
      soil solution composition associated with sub-surface wastewater irrigation.

PMID- 11827343
TI  - Comment on "Evaluation of biofilm image thresholding methods".

PMID- 11827344
TI  - Modern scientific methods and their potential in wastewater science and
      technology.
AB  - Application of novel analytical and investigative methods such as fluorescence in
      situ hybridization, confocal laser scanning microscopy (CLSM), microelectrodes
      and advanced numerical simulation has led to new insights into micro- and
      macroscopic processes in bioreactors. However, the question is still open whether
      or not these new findings and the subsequent gain of knowledge are of significant
      practical relevance and if so, where and how. To find suitable answers it is
      necessary for engineers to know what can be expected by applying these modern
      analytical tools. Similarly, scientists could benefit significantly from an
      intensive dialogue with engineers in order to find out about practical problems
      and conditions existing in wastewater treatment systems. In this paper, an
      attempt is made to help bridge the gap between science and engineering in
      biological wastewater treatment. We provide an overview of recently developed
      methods in microbiology and in mathematical modeling and numerical simulation. A
      questionnaire is presented which may help generate a platform from which further
      technical and scientific developments can be accomplished. Both the paper and the
      questionnaire are aimed at encouraging scientists and engineers to enter into an
      intensive, mutually beneficial dialogue.

PMID- 11827345
TI  - Microbiological aspects of a bioreactor with submerged membranes for aerobic
      treatment of municipal wastewater.
AB  - An aerobic membrane bioreactor treating municipal wastewater at complete biomass
      retention was studied in respect of microbiological parameters over a period of
      380 days. The results were compared to those obtained from a conventional
      activated sludge wastewater treatment plant (WWTP) treating the same wastewater.
      Microscopically, significant changes in the structure of the flocs and of the
      ratio between free suspended and aggregated cells could be observed. The presence
      of filamentous bacteria varied from almost not present to very high numbers. With
      the exception of short periods after changes in operating conditions, protozoa
      and metazoa were rarely present in the sludge community. The rate of oxygen
      consumption and the cell detectability by fluorescence in situ hybridizatio
      (FISH) with rRNA-targeted oligonucleotide probes were used to assess the
      physiological state of the bacterial cells Oxygen consumption rates of sludge
      samples obtained from both the conventional and membrane filtration plant wer
      determined without and after addition of different energy and carbon sources. In
      contrast to the conventional activate sludge, a pronounced increase in
      respiration activity upon the addition of organic substrates could be observed in
      th membrane filtration sludge. In situ probing with the Bacteria-specific probe
      EUB338 visualized 40-50% of all DAPI stainable bacteria in the membrane
      bioreactor, compared to 80% cells detectable by FISH in the conventional activate
      sludge. These results suggest that bacteria present in the highly concentrated
      biomass of the membrane reactor use the energy supplied for their maintenance
      metabolism and were not in a physiological state characteristic for growth This
      assumption could explain the zero net biomass production observed in the reactor.

PMID- 11827346
TI  - Characterization of denitrifying phosphate-accumulating organisms cultivated
      under different electron acceptor conditions using polymerase chain reaction
      denaturing gradient gel electrophoresis assay.
AB  - To investigate the characteristics and the microbial diversity of denitrifying
      phosphate-accumulating organisms (DNPAOs) that are capable of conducting enhanced
      biological phosphorus removal (EBPR) using nitrate as electron acceptor, three
      sequencing batch reactors were operated under three different electron acceptor
      conditions, i.e., only oxygen, oxygen together with nitrate and only nitrate.
      Based on the chemical analysis concerning the biochemical transformation of each
      reactor, it was found that phosphate-accumulating organisms responsible for EBPR
      consisted of at least three populations including DNPAOs, and that the microbial
      community structure was changed according to the electron acceptor conditions.
      Also, the sludge cultivated with oxygen together with nitrate showed a drastic
      increase in the amount of phosphorus uptake under anoxic conditions, which
      suggested that a proportion of DNPAOs capable of utilizing nitrate under aerobic
      conditions were present. On the other hand, the change in microbial community
      structure depending on the type of electron acceptor was demonstrated by the
      analysis of the results of denaturing gradient gel electrophoresis of polymerase
      chain reaction-amplified 16S ribosomal DNA fragments. It was found that the
      bacteria commonly contained in all the reactors were Rhodocyclus sp. (96%
      identity) and Dechlorimonas sp. (97% identity) that belonged to the beta subclass
      of Proteobacteria on the basis of the analysis of the sequence excised from DGGE
      bands and the determination of phylogenetic affiliation. However, only the
      presence of Rhodocyclus sp. in all the reactors was demonstrated by fluorescent
      in situ hybridization analysis.

PMID- 11827347
TI  - Performance of a bioreactor with submerged membranes for aerobic treatment of
      municipal waste water.
AB  - Aerobic treatment of municipal waste water in a membrane bioreactor was studied
      for 535 d. Apart from sampling, sludge was retained completely by a submerged
      hollow fibre membrane with a pore-size of 0.2 microm. The pilot plant comprised
      an anoxic zone to enable denitrification. The maximum liquid hold-up of the plant
      was 3.9 m3. In this study the reactor performance and the stability of the
      process and the membrane capacity were investigated. A stable flux of 181 m(-2)h(
      1) could be realised with a mean transmembrane pressure difference of 0.3bar with
      air-bubbling and backflushing the membrane and cleaning it in place every two
      months for one or two hours. For about 140d, a flux of 271 m(-2)h(-1) was
      achieved, but cleaning became necessary more often. The hydraulic retention time
      (HRT) varied between 10.4 and 15.6h. Accordingly the volumetric loading rate was
      between 1.1 and 1.7kg CODm(-3)d(-1). No inoculum was used. The mixed liquor
      suspended solids (MLSS) concentration gradually increased to 18-20g MLSSl(-1).
      The feed to microorganism (F/M) ratio varied according to the operation
      conditions but decreased against a value of 0.07 kg COD kg(-1) MLSSd(-1).
      Treatment performance was very stable and on a high level. The COD was reduced by
      95%. Nitrification was complete and up to 82% of the total nitrogen could be
      denitrified.

PMID- 11827348
TI  - Enumeration of acetate-consuming bacteria by microautoradiography under oxygen
      and nitrate respiring conditions in activated sludge.
AB  - Microautoradiography was used to enumerate bacteria able to take up radiolabelled
      acetate in activated sludge using oxygen or nitrate as electron acceptors. In
      each of three wastewater treatment plants (WWTP) with nitrification and
      denitrification (N-removal), the number of bacteria consuming acetate under
      aerobic and anoxic conditions was identical in contrast to the acetate removal
      rates. The rates were clearly lower under anoxic conditions suggesting that the
      specific activity of the cells and not the number of active cells was reduced
      under anoxic conditions. The fraction of bacteria able to consume acetate varied
      in three WWTPs between 47% and 93% of the total number of bacteria as determined
      by DAPI. In a WWTP without N-removal only 20% of the bacteria were able to
      consume acetate under aerobic conditions and very few of these were able to do it
      under anoxic conditions. The cell specific acetate removal rates in all WWTPs
      were found to be 3.0-13.2 x 10(-15) mol cell(-1) h(-1) under aerobic conditions
      and between 1.9 and 9.1 x 10(-15) mol cell(-1) h(-1) under anoxic conditions.

PMID- 11827349
TI  - Microbial community analysis of thermophilic contact oxidation process by using
      ribosomal RNA approaches and the quinone profile method.
AB  - Microbial community structure of a lab scale thermophilic aerobic wastewater
      treatment reactor was analyzed by a combination of culture-independent methods.
      Quinone profile method provides for chemical analysis of respiratory quinone
      molecular species, which corresponds to bacterial groups. Denaturing gradient gel
      electrophoresis (DGGE) of PCR-amplified 16S rDNA partial sequences (PCR-DGGE)
      clarifies community changes at species level, as DGGE can separate DNA fragments
      of different sequences. Certain phvlogenetic groups of bacterial cells can be
      labeled by fluorescence in situ hybridization (FISH). Quinone profile showed a
      predominant presence of MK-7. PCR-DGGE revealed that constituents of the
      community were unchanged during the stable phase. FISH demonstrated the existence
      of the relatives of Bacillus lentus and B. thermocloacae in considerable
      proportions. The community was mainly composed of Bacillaceae, and obligate
      thermophilic and mesophilic Bacillus appeared in spite of the temperature
      fluctuation from 35 degrees C to 60 degrees C. The combination of these culture
      independent methods revealed the community precisely enough to evaluate the
      reactor performance.

PMID- 11827350
TI  - Active biomass in activated sludge mixed liquor.
AB  - The engineering and technology of the activated sludge system are reasonably well
      established, with systems implemented worldwide for the biological removal of C,
      N and/or P. Parallel to this development, significant advances have been made in
      the microbiological and biochemical areas of activated sludge. These advances
      have been driven by the development of new analytical techniques that allow
      microorganisms to be studied in situ in the activated sludge environment.
      However, there has been little cross-linking and overlap between the engineering
      and technology and microbiology and biochemistry paradigms. In particular, the
      information from the microbiology and biochemistry has not been integrated into
      the engineering and technology paradigm, to enable improved system design and
      optimization. One area that can form a starting point to build bridges between
      the two paradigm sets, is measurement of active biomass. The current design and
      simulation models invariably include active biomass for each organism group as
      fundamental parameters which define quantitatively the kinetic rates of the
      relevant biological processes. However, these parameters remain purely
      hypothetical because to date they have not been quantitatively measured; their
      acceptance is based on the consistency of model predicted results over a wide
      range of application. This paper describes developments in quantitative
      measurement of the heterotrophic and autotrophic active biomass concentrations
      within the engineering and technology paradigm, and the formulation of a
      multinational project which will attempt to link these measurements and the
      defined engineering environment to the new microbiological and biochemical
      analytical techniques. It is hoped that this project will facilitate integration
      of the two paradigms sets.

PMID- 11827351
TI  - Role of filamentous microorganisms in activated sludge foaming: relationship of
      mycolata levels to foaming initiation and stability.
AB  - The relationship between the levels of mycolic acid-containing actinomycetes
      (mycolata), Gordonia spp. and Gordonia amarae, and foam initiation and stability
      was characterized using: (1) batch tests involving addition of G. amarace cells
      to activated sludge, (2) analysis of a full-scale activated sludge plant that
      experienced seasonal foaming, and (3) a study of lab-scale activated sludge
      reactors augmented with G. amarae. Using batch tests, threshold Gordonia levels
      for foam formation and foam stability were determined to be approximately 2 x
      10(8) microm ml(-1) and 1 x 10(9) microm ml(-1), respectively. In the full-scale
      plant, the levels of Gordonia spp. and G. amarae increased during the course of
      foaming, and the foam formation threshold of 2 x 10 microm ml(-1) corresponded to
      the onset of foaming. This value was also verified in lab-scale reactor washout
      experiments, where decreasing mycolata levels were observed during the course of
      foam dissipation. The foam stability threshold of 1 x 10(9) micorm ml(-1) was
      verified in lab-scale reactor studies. The increase in the levels of Gordonia
      spp. and G. amarae in the full-scale plant corresponded to an increase in
      temperature, suggesting that the growth of Gordonia spp. was favored during
      warmer periods.

PMID- 11827352
TI  - Assessment of activated sludge viability with flow cytometry.
AB  - The aim of the study was to evaluate the applicability of fluorescent dyes and
      multiparameter flow cytometry for the rapid and direct viability/activity
      assessment of activated sludge samples taken from wastewater treatment plants.
      Viability and activity of the biomass were estimated respectively through
      cellular membrane integrity, staining with SYBR Green I and Propidium Iodide, and
      through fluorogenic dyes capable of detecting enzymatic activity, as FDA and
      BCECF-AM. A procedure has been developed to disaggregate sludge flocs before dyes
      staining and cytometric analysis. The developed procedure allows a high recovery
      of bacteria with good accuracy and repeatability, and minimize the damage of the
      cells suspension obtained from the disaggregation of the flocs. These
      measurements were applied to estimate the two main parameters required to define
      the biological activated sludge process: the endogenous decay rate and the
      specific growth rate in exponential phase with high F/M ratio. Oxygen utilization
      rate measurements (OUR) were conducted to conventionally monitor the activity of
      the biomass. The preliminary data are encouraging and support the possibility to
      investigate bacteria dynamics on wastewater treatment plants.

PMID- 11827353
TI  - Nitrifying and heterotrophic population dynamics in biofilm reactors: effects of
      hydraulic retention time and the presence of organic carbon.
AB  - Two biofilm reactors operated with hydraulic retention times of 0.8 and 5.0 h
      were used to study the links between population dynamics and reactor operation
      performance during a shift in process operation from pure nitrification to
      combined nitrification and organic carbon removal. The ammonium and the organic
      carbon loads were identical for both reactors. The composition and dynamics of
      the microbial consortia were quantified by fluorescence in situ hybridization
      (FISH) with rRNA-targeted oligonucleotide probes combined with confocal laser
      scanning microscopy, and digital image analysis. In contrast to past research,
      after addition of acetate as organic carbon nitrification performance decreased
      more drastically in the reactor with longer hydraulic retention time. FISH
      analysis showed that this effect was caused by the unexpected formation of a
      heterotrophic microorganism layer on top of the nitrifying biofilm that limited
      nitrifiers oxygen supply. Our results demonstrate that extension of the hydraulic
      retention time might be insufficient to improve combined nitrification and
      organic carbon removal in biofilm reactors.

PMID- 11827354
TI  - Sludge population optimisation: a new dimension for the control of biological
      wastewater treatment systems.
AB  - The activated sludge comprises a complex microbiological community. The structure
      (what types of microorganisms are present) and function (what can the organisms
      do and at what rates) of this community are determined by external physico
      chemical features and by the influent to the sewage treatment plant. The external
      features we can manipulate but rarely the influent. Conventional control and
      operational strategies optimise activated sludge processes more as a chemical
      system than as a biological one. While optimising the process in a short time
      period, these strategies may deteriorate the long-term performance of the process
      due to their potentially adverse impact on the microbial properties. Through
      briefly reviewing the evidence available in the literature that plant design and
      operation affect both the structure and function of the microbial community in
      activated sludge, we propose to add sludge population optimisation as a new
      dimension to the control of biological wastewater treatment systems. We stress
      that optimising the microbial community structure and property should be an
      explicit aim for the design and operation of a treatment plant. The major
      limitations to sludge population optimisation revolve around inadequate
      microbiological data, specifically community structure, function and kinetic
      data. However, molecular microbiological methods that strive to provide that data
      are being developed rapidly. The combination of these methods with the
      conventional approaches for kinetic study is briefly discussed. The most pressing
      research questions pertaining to sludge population optimisation are outlined.

PMID- 11827356
TI  - Simultaneous P and N removal in a sequencing batch biofilm reactor: insights from
      reactor- and microscale investigations.
AB  - A sequencing batch biofilm reactor (SBBR) with well established enhanced
      biological phosphate removal (EBPR) was subjected to higher ammonium
      concentrations to stimulate and eventually implement simultaneous nitrification.
      Changes of activity and populations were investigated by a combination of online
      monitoring, microsensor measurements and fluorescence in situ hybridisation
      (FISH) of biofilm sections. Nitrification and nitrifying bacteria were always
      restricted to the periodically oxic biofilm surface. Both, activity and
      population size increased significantly with higher ammonium concentrations.
      Nitrification always showed a delay after the onset of aeration, most likely due
      to competition for oxygen by coexisting P accumulating and other heterotrophic
      bacteria during the initial aeration phase. This view is also supported by
      comparing oxygen penetration and oxygen uptake rates under low and high ammonium
      conditions. Therefore, simultaneous nitrification and phosphorus removal in a P
      removing SBBR appears to be only possible with a sufficiently long oxic period to
      ensure oxygen availability for nitrifiers.

PMID- 11827355
TI  - Population changes in a biofilm reactor for phosphorus removal as evidenced by
      the use of FISH.
AB  - Induction of denitrification was investigated for a lab-scale phosphate removing
      biofilm reactor where oxygen was replaced with nitrate as the electron acceptor.
      Acetate was used as the carbon source. The original biofilm (acclimatised with
      oxygen) was taken from a well-established large-scale reactor. During the first
      run, a decrease in the denitrifying bio-P activity was observed after 1 month
      following a change in the anaerobic phase length. This was initially interpreted
      as a shift in the microbial population caused by the changed operation. In the
      second run, biomass samples were regularly collected and analysed by fluorescent
      in situ hybridisation (FISH) and confocal laser scanning microscopy (CLSM).
      Concurrently, samples were taken from the original reactor with oxygen as
      electron acceptor in order to investigate natural microbial fluctuations. A
      similar decrease in the activity as in the first run was seen after one month,
      although the phase lengths had not been varied. Hence, the decrease after 1 month
      in the first and second run should be seen as a start-up phenomenon. FISH could
      detect a noticeable shift in the microbial population mainly within the first 2
      weeks of operation. Almost all bacteria belonging to the alpha subclass
      disappeared and characteristic clusters of the beta and gamma subclasses were
      lost. Small clusters of gram-positive bacteria with a high DNA G + C content
      (GPBHGC) were gradually replaced by filamentous GPBHGC. Most of the bacteria in
      the denitrifying, phosphate removing biofilm belonged to the beta subclass of
      Proteobacteria. The applied set of gene probes had been selected based on
      existing literature on biological phosphate removing organisms and included a
      recently published probe for a Rhodocyclus-like clone. However, none of the
      specific probes hybridised to the dominant bacterial groups in the reactors
      investigated. No noticeable changes were detected in the aerobic bench-scale
      reactor during this period, indicating that the observed changes in the lab-scale
      reactor were caused by the changed environment.

PMID- 11827357
TI  - Cyclo-oxygenase-1 and cyclo-oxygenase-2 and cardiovascular system.
AB  - Prostaglandins play important roles in the pathophysiological mechanism of action
      of platelets and endothelial cells in the cardiovascular system. The two isoforms
      of cyclo-oxygenase, respectively cyclo-oxygenase-1 and cyclo-oxygenase-2, are
      differently expressed in these cells. Activated platelets show a relatively large
      amount of cyclo-oxygenase-1, whereas endothelial cells have the gene for cyclo
      oxygenase-2, the expression of which follows cell activation. In the
      atherosclerosis lesion, prostaglandin synthesis is mainly mediated by the
      inducible cyclo-oxygenase-2 expressed in macrophages/foam cells, smooth muscle
      cells and endothelial cells. Aspirin, a selective platelet cyclo-oxygenase-1
      inhibitor still remains the most extensively studied antiplatelet agent, even
      though there is growing evidence that many other compounds could be valuable
      either in association, or alternatives in antithrombotic therapy.

PMID- 11827358
TI  - Cyclo-oxygenase isoenzymes. Structural basis for selective inhibition of cyclo
      oxygenases by anti-inflammatory agents.
AB  - Cyclo-oxygenase (prostaglandin endoperoxide synthase) is the enzyme which
      metabolizes the conversion of arachidonic acid to prostaglandin. It exists in at
      least two isoforms: the constitutive (cyclo-oxygenase-1) and the inducible (cyclo
      oxygenase-2) which is controlled by a number of factors, including cytokines and
      intracellular messengers. These enzymes are the therapeutic targets of non
      steroidal anti-inflammatory drugs such as aspirin and ibuprofen. The cyclo
      oxygenase active site is a long, hydrophobic, channel where the substrate
      arachidonic acid gains access to the active site. Cyclo-oxygenase-2 differs form
      cyclo-oxygenase-1 in certain key characteristics, particularly important is the
      valine/leucine substitution at position 523 that creates a defect in the inner
      shell of the cyclo-oxygenase-2 enzyme channel leaving a side pocket by which
      drugs selective for cyclo-oxygenase-2 gain access. Although cyclo-oxygenase-1
      seems to be expressed in physiological conditions and cyclo-oxygenase-2 in
      inflammatory conditions, it is not yet possible to identify all their different
      roles. Cyclo-oxygenase-2 may be expressed constitutively, whereas the generation
      of prostaglandin by cyclo-oxygenase-2 may replace that by cyclo-oxygenase-1 in
      some situations (or vice-versa). Both cyclo-oxygenase isoenzymes contribute to
      mucosal defence and the inhibition of the two isoforms contributes to the
      pathogenesis of non-steroidal anti-inflammatory drug-induced gastric damage.

PMID- 11827359
TI  - Selective cyclo-oxygenase-2 inhibitors: cardiovascular and gastrointestinal
      toxicity.
AB  - The introduction of selective inhibitors of cyclo-oxygenase-2 to the marketplace
      has been much anticipated for several years. It would appear that these compounds
      have lived up to the expectations of having reduced gastrointestinal toxicity
      and, at least for some indications, of efficacy similar to that of conventional
      non-steroidal anti-inflammatory drugs. However, there is a growing body of
      evidence suggesting that cyclo-oxygenase-2 plays a very important role in
      gastrointestinal mucosal defence, particularly in situations in which the mucosa
      is damaged or inflamed. Moreover, physiological roles for cyclo-oxygenase-2 both
      in the renal and cardiovascular systems are becoming better recognized.
      Inhibition of cyclo-oxygenase-2 can lead to peripheral oedema and hypertension,
      and may promote thrombosis. Indeed, there is recent evidence of increased rates
      of myocardial infarction in arthritis patients taking a selective cyclo-oxygenase
      2 inhibitor. Use of low-dose aspirin concurrently with use of a selective cyclo
      oxygenase-2 inhibitor may provide some degree of protection against the potential
      cardiovascular toxicity of the latter but both laboratory and clinical studies
      suggest that the concomitant use of these two types of drugs results in
      gastrointestinal ulceration comparable to what is seen with conventional non
      steroidal anti-inflammatory drugs. These recent results suggest that care must be
      exercised in the use of selective cyclo-oxygenase-2 inhibitors by individuals who
      are at increased risk of myocardial infarction and stroke, and the use of low
      dose aspirin by these patients may place them at increased risk of
      gastrointestinal complications.

PMID- 11827360
TI  - Cyclo-oxygenase-1/cyclo-oxygenase-2 non selective non-steroidal anti-inflammatory
      drugs: epidemiology of gastrointestinal events.
AB  - Non-steroidal anti-inflammatory drug use is associated with gastrointestinal side
      effects including complications such as bleeding and perforation, which occur in
      1-2% of patients after 6-12 months of therapy. A high level of non-prescription
      non-steroidal anti-inflammatory drug use is observed among those presenting
      complications. More common side-effects are symptomatic gastro-duodenal ulcers
      (annual incidence of 4-8%) and dyspepsia (25-50%). Low-dose aspirin use is also
      associated with an increased risk of upper gastrointestinal bleeding, but the
      increase is about 3 times lower than that found with common non-steroidal anti
      inflammatory drugs. Recent studies suggest that the risk of bleeding in patients
      taking preferential cyclooxygenase-II inhibitors (e.g. nimesulide) is similar to
      that in patients taking non-selective non-steroidal anti-inflammatory drugs.
      Epidemiological studies have also shown that nitric oxide donors and
      antisecretory drugs reduce the risk of upper gastrointestinal bleeding both in
      non-steroidal anti-inflammatory drug and low-dose aspirin users.

PMID- 11827361
TI  - Mechanism of non-steroidal anti-inflammatory drug-gastropathy.
AB  - Non-steroidal anti-inflammatory drugs are recognized to cause gastrointestinal
      damage impairing the defense ability of gastric mucosal barrier. A variety of
      mechanisms due to non-steroidal anti-inflammatory drugs direct irritant (topical)
      action and to their main pharmacological (systemic) effect, is involved in the
      pathogenesis of non-steroidal anti-inflammatory drugs induced gastropathy. The
      systemic activity comprises the inhibition of cyclo-oxygenase, but an increasing
      body of evidence suggests that cyclo-oxygenase-independent mechanisms are
      involved in the development of gastric injury. In line with this concept, neither
      cyclo-oxygenase-1 nor cyclo-oxygenase-2 deficient mice develop spontaneous
      gastrointestinal ulcers and pharmacological inhibition of cyclo-oxygenase-1 or
      cyclo-oxygenase-2 with selective inhibitors doesn't elicit gastrointestinal
      damage; suggesting that both isoforms of cyclo-oxygenase enzymes have to be
      inhibited to induce ulcers. Moreover non-steroidal anti-inflammatory drugs
      administration in rats, induces the systemic release of tumor necrosis factor
      alpha and drives gastric epithelial cells to apoptosis activating the pro
      apoptotic cascade of caspases. In response to non-steroidal anti-inflammatory
      drugs, neutrophils are recruited into the gastric microcirculation through a
      process that requires activation of adhesion molecules. Although there is
      virtually no information regarding the regulation of expression of gastric
      endothelial cell adhesion molecules in response to non steroidal anti
      inflammatory drugs, the nuclear factor-kB may represent a potential modulator.
      Supporting this view, selective proteasome inhibitors inhibit nuclear
      translocation of nuclear factor-kB induced by tumor necrosis factor-alpha in
      human endothelial cells in vitro and reduce indomethacin-induced gastric mucosal
      injury in vivo.

PMID- 11827362
TI  - Prophylaxis and treatment of non-steroidal anti-inflammatory drug-induced upper
      gastrointestinal side-effects.
AB  - The use of specific agents to heal mucosal lesions or to prevent non-steroidal
      anti-inflammatory drug toxicity, has focused upon two approaches: replacement of
      prostaglandin deficiency and inhibition of acid secretion. Acid suppression with
      traditional ulcer healing doses of H2-blockers is effective in healing gastric
      and duodenal ulcers upon discontinuation of the offending drug. In the event the
      non-steroidal anti-inflammatory drug must be continued, the use of H2-blockers is
      associated with a decrease in the healing rate. In long-term prevention studies,
      H2-blockers significantly reduce duodenal ulcer rates, but are ineffective in
      reducing gastric ulceration. More potent acid inhibition with a double-dose of H2
      blockers (famotidine 80 mg daily, ranitidine 600 mg daily) may reduce the risk of
      gastric and duodenal ulcers. Marked acid suppression with proton pump inhibitors
      (omeprazole 20-40 mg, lansoprazole 30 mg daily) also appears to be very effective
      in healing gastric and duodenal ulcers in patients continuing the offending drug
      as well. An analysis of pooled data from comparative studies on omeprazole vs
      ranitidine, misoprostol and sucralfate shows a therapeutic advantage in favour of
      the proton pump inhibitor, ranging from 10 to 40%. In long-term prevention
      studies, omeprazole (20 mg daily) and pantoprazole (40 mg daily) have also been
      shown to reduce the risk of gastric and duodenal ulcers and non-steroidal anti
      inflammatory drug-related dyspepsia. Current data from recent comparative studies
      of omeprazole (20 mg daily) vs ranitidine (150 mg daily) and misoprostol (200
      microg daily) showed that, after 6 months' follow-up, the proton pump inhibitor
      was significantly superior to control drugs in reducing the risk both of gastric
      and duodenal ulcer. Misoprostol (at doses ranging from 400 microg to 800
      microg/day) is an effective form of therapy for preventing non-steroidal anti
      inflammatory drug-induced gastroduodenal lesions. However high-dose misoprostol
      only, seems adequate for the prevention of ulcer complications, mainly in high
      risk non-steroidal anti-inflammatory drug users. Thus, available data are
      undoubtedly in favour of the proton pump inhibitors as well tolerated and
      effective drugs in the prophylaxis and treatment of non-steroidal anti
      inflammatory drug-related mucosal lesions in the gastrointestinal tract.

PMID- 11827363
TI  - Analgesia and cyclo-oxygenase inhibitors.
AB  - Non-steroidal anti-inflammatory drugs are among the most commonly used
      medications and they are a mainstay in the treatment of inflammatory diseases.
      Non-steroidal anti-inflammatory drugs are widely used to reduce pain associated
      with acute or chronic inflammation. Recently, a new class of inhibitors of the
      inducible enzyme cyclo-oxygenase-2 have become available. These inhibitors
      selectively target the inducible enzyme and have been shown to spare the
      gastrointestinal tract. While a role of cyclo-oxygenase-2 in the development of
      chronic inflammation has been well established, its role in pain perception is
      still unclear. Recent experimental data led to the hypothesis that cyclo
      oxygenase-1 plays an important role in pain perception. This short review
      addresses some recent preclinical data as well as some clinical evidence showing
      that cyclo-oxygenase-1 is an important component of inflammatory pain.

PMID- 11827364
TI  - Endoscopic transumbilical subglandular augmentation mammaplasty.
AB  - This technique has provoked many controversial comments. With modification and
      adequate clinician training and experience, however, the results can improve, and
      complications can be minimized. The author's complications occurred in the early
      stages of the use of this method; as experience was gained, they decreased.
      Furthermore, fewer and less severe complications occurred when the techniques
      were modified, including using instrument dissection before tissue expansion,
      better patient selection, early massage, and more frequent postoperative follow
      up visits. In addition, this method leaves no scar at the breast and allows a
      quicker recovery. Most patients who underwent this procedure have been pleased
      with their results. Transumbilical endoscopic bilateral augmentation mammaplasty
      is an attractive alternative technique, and with careful patient selection,
      operative modification, and technical expertise, results can be achieved
      comparable with an open subglandular augmentation.

PMID- 11827365
TI  - New research in breast reconstruction: adipose tissue engineering.
AB  - In the human species, a major function of the breast is aesthetic. The soft
      tissue volume within the breast displaces the overlying skin to create the
      protuberant contour of the female thorax, that is solidly associated with, and to
      some extent, definitive of, femininity in modern culture. Adipose tissue is the
      major contributor to the volume of the breast.

PMID- 11827366
TI  - The political, legal, and financial issues that plastic surgery is facing and how
      to develop a plan to cope.
AB  - Our specialty has been a creative wonder and an outright blessing to mankind. We
      have honed the arts of soft-tissue reconstruction to a level never thought
      possible just 100 years ago. We have found solutions to wound problems long after
      others have given up. We have restored the destroyed features of people ravaged
      by disease, life circumstances, and the acts of war. We have treated the deformed
      child, the patient with cancer, and reversed the signs of age. But as Thomas
      Sowell states in his article in 1994 in Forbes Magazine on the 100th anniversary
      of the birth of Fredrich Hayek, the author of The Road to Serfdom, the rule of
      law, which Hayek saw as crucial to the economy and to the survival of freedom, is
      nowhere in greater danger than in the supreme court of the United States. Sowell
      warned of the process going on that would bring socialism to our health care
      delivery system. He goes on to assert that it will be paid for by "loss of
      freedom to make our own decisions about medical care that are literally questions
      of life and death. The key to the future of medicine is now in our hands. This
      key will open the door to every doctor's dream of having the technologies that
      will allow physicians to diagnose and treat all the physical ills of the human
      race. Or the key, on the other hand, could open the exit door through which the
      best and brightest will leave medicine, feeling that they no longer can take on
      the legal and the financial risks to themselves and their families. The road to
      freedom from the controlling factors noted will require a change in culture.
      Knowing these facts will allow the plastic surgeon in practice to accept these
      factors and work with them to provide better care for their patients.

PMID- 11827367
TI  - Controlled bone regeneration: the ultimate process in bone repair.
AB  - The main goal of bone healing, besides the healing of the bone, is ensuring that
      the dynamic system of repair is under biologic control. To do so, the soft tissue
      has to be kept isolated to avoid any herniation into the bony defect, that would
      produce and interfere with the bone interface or collapse the original defect
      resulting in a relapse.

PMID- 11827368
TI  - Skin resurfacing for the burned patient.
AB  - It has been estimated that 2 million people per year have burns requiring medical
      attention in the United States. The available and expert clinicians in dedicated
      burn centers around the country have cared successfully for these patients and
      given them a second chance at a functional life. It still behooves current-day
      plastic surgeons to be knowledgeable and adept in their care, not only because
      they may be called upon at times to manage some of the smaller acute burns, but
      also because many of the general principles of burn reconstruction and wound
      management are relevant to other areas of general plastic surgery. Acute burns
      should be dealt with like any other major trauma with the ABCs of aggressive
      resuscitation and airway management. Like any other wound, debridement and
      nutrition are important (i.e., early escharectomy of the burn wound and enteral
      nutrition during the hypermetabolic state). Early coverage of the open wound is
      essential to limit bacterial colonization and prevent infection and to reduce
      fluid and electrolyte and heat loss. If autografts are not available immediately,
      temporary coverage with one of the above-mentioned barrier materials should be
      used. Still, autografts, when available, should be the burn surgeon's first
      choice. Donor sites may be reharvested to provide more autograft than was
      anticipated with large-percentage TBSA burns. Physicians should keep in mind the
      advantages (and disadvantages) of using the scalp and back. As far as research
      and technological advances in the area of plastic surgery, burn surgery may be
      the most progressive, with the evolution of biologic tissue-engineered skin
      substitutes and the research of growth factors in healing. Further improvements
      in tissue engineering and technology should result in even more effective skin
      substitutes and hence better functional and aesthetic outcomes with economic
      efficiency in large burns.

PMID- 11827370
TI  - New microsurgical applications: implications for the infrastructures of plastic
      surgery.
AB  - As a technical innovation, microsurgery has changed concepts and strategies
      throughout plastic surgery. The infrastructures of plastic surgery currently are
      evolving in ways that make the identity and future of the specialty uncertain.
      Microsurgery also may be a basis for fresh thoughts in these areas of
      infrastructure. This article touched on some areas where microsurgery could be an
      important element in organizational development, namely patient population
      identification, economic strategies, academic organization, and medical
      education. More thorough exploration of these ideas and identification of others
      may result in a new foundation for plastic surgery with microsurgery as a key
      element.

PMID- 11827369
TI  - New directions in laser therapy: combination of carbon dioxide laser resurfacing
      and incisional cosmetic facial surgery.
AB  - As clinicians enter a time of increasingly greater patient demand for quality of
      surgery, superior results, and efficient time use, the plastic surgeon should
      have as many tools as possible to accomplish these ends. Patient safety should
      never be compromised, however. A thorough analysis of the patient regarding
      physical complaints and social and medical history is of utmost importance. The
      guidelines that have been enumerated are just that-guidelines. Still, the plastic
      surgeon must use all of his or her experience and knowledge to formulate the best
      and most appropriate surgical plan for each individual patient.

PMID- 11827372
TI  - A prototype industrial sensing system for phosphorus based on micro system
      technology.
AB  - Progress in the development of a miniaturised microfluidic instrument for
      monitoring phosphorus in natural waters and wastewater is presented. The yellow
      colorimetric method for phosphate analysis has been transferred to a microfluidic
      chip configuration This simple method employs one reagent mixed in a 1:1 ratio
      with a sample to produce a yellow colour absorbing strongly below 400 nm. A
      stopped flow approach is used which, together with the very rapid kinetics and
      simple reagent stream, enables a very uncomplicated microfluidic manifold design
      to be adopted. The working wavelength is 380 nm to coincide with the peak output
      of a recently developed UV-LED narrow bandwidth light source. The limit of
      detection for the yellow method is 0.2 ppm with a dynamic linear range from 0-50
      ppm possible. The reaction time at room temperature is less than 3 min, which
      means that up to 20 samples per hour can be analysed.

PMID- 11827371
TI  - Refinements in abdominoplasty.
AB  - When performing traditional abdominoplasty, three fundamental defects of the
      abdominal wall must always be addressed by the plastic surgeon. They include
      redundant skin, excess fat, and musculofascial laxity. Plastic surgeons have
      found that this procedure consists of dermolipectomy and rectus plication,
      extremely effective in restoring the abdomen to its youthful shape in the vast
      majority of patients. This article will review the recent advancements in body
      contouring surgery while focusing on the recent technical refinements in
      abdominoplasty.

PMID- 11827373
TI  - L-malic acid biosensor for field-based evaluation of apple, potato and tomato
      horticultural produce.
AB  - A screen-printed three-electrode amperometric biosensor incorporating malic
      enzyme for the measurement of L-malic acid in apple, potato and tomato
      horticultural samples has been developed. The working electrode contained 0.38 mU
      of immobilised enzyme and was fabricated using rhodinised carbon to facilitate
      NADPH oxidation at an operating potential of +300 mV vs. Ag/AgCl compared with >
      +600 mV for bare carbon. The linear range of the sensor was 0.028-0.7 mM L-malic
      acid with relative standard deviations of 3.3-13.3%. When testing with real
      apple, potato and tomato samples, the sensor accuracy was within 13.7% of a
      standard commercially available photometric test kit. The sensor approach is
      cheap, simple to perform and rapid (6 min), requiring only buffer-electrolyte and
      a small sample volume.

PMID- 11827374
TI  - A mid-IR flow-through sensor for direct monitoring of enzyme catalysed reactions.
      Case study: Measurement of carbohydrates in beer.
AB  - A novel mid-IR flow-through sensor for in situ monitoring of the enzymatic
      reaction of amyloglucosidase with carbohydrates was developed. Amyloglucosidase
      was immobilised on agarose beads with N-ethyl-N'-(3
      dimethylaminopropyl)carbodiimide hydrochloride (EDC) and directly placed in a
      conventional IR flow-through cell. The carbohydrate content of various beer
      samples was then determined by following the enzymatic hydrolytic cleavage of
      carbohydrates to glucose with Fourier-transform infrared (FTIR) spectroscopy. The
      whole procedure was done in an automated way operating in the stopped flow mode
      by incorporating the flow-through sensor in a sequential injection (SI) manifold.
      As the immobilised enzyme was directly probed by the IR beam, an in situ study of
      the enzymatic reaction was possible enabling determination of the Michaelis
      Menten constant of the immobilised enzyme. A linear calibration curve was
      recorded using maltose standards in the range between 0.86 and 7.13 g L(-1). The
      proposed method was successfully applied to the determination of the carbohydrate
      content of four different beer samples by the standard addition method. Moreover
      experiments showed the possibility of monitoring in situ the immobilisation of
      the enzyme as well as a small organic acid (malic acid) on the agarose beads
      using EDC.

PMID- 11827375
TI  - A fluorescent PEBBLE nanosensor for intracellular free zinc.
AB  - The development and characterisation of a fluorescent optical PEBBLE (Probe
      Encapsulated By Biologically Localised Embedding) nanosensor for the detection of
      zinc is detailed. A ratiometric sensor has been fabricated that incorporates two
      fluorescent dyes; one is sensitive to zinc and the other acts as a reference. The
      sensing components are entrapped within a polymer matrix by a microemulsion
      polymerisation process that produces spherical sensors that are in the size
      region of 20 to 200 nm. Cellular measurements are made possible by the small
      sensor size and the biocompatibility of the matrix. The effects of reversibility,
      photobleaching and leaching have been examined, as well as the selectivity
      towards zinc over other cellular ions such as Na+, Ca2+, K+, and Mg2+. The
      dynamic range of these sensors was found to be 4 to 50 microM Zn2+ with a linear
      range from 15 to 40 microM. The response time for the PEBBLE is less than 4 s and
      the sensor is reversible. In addition, the nanosensors are photostable and
      leaching from the matrix, determined using a novel method, is minimal. These
      sensors are capable of real-time inter- and intra-cellular imaging and are
      insensitive to interference from proteins.

PMID- 11827376
TI  - A direct comparison of amperometric gas sensors with gas-diffusion and ion
      exchange membrane based electrodes.
AB  - The effect of the nature of the working electrode used in amperometric gas
      sensors on the performance criteria of sensitivity, detection limit, gas flow
      rate and humidity dependence was evaluated. The arrangement based on metallized
      ion-exchange membranes (Nafion) was compared with gas-diffusion electrodes based
      on porous poly(tetrafluoroethylene) (PTFE) with metallic electrodes deposited on
      the rear side. Two representative analyte gases were chosen: SO2, which has fast
      reaction kinetics, and NO, which has slow reaction kinetics. It was found that
      both types of electrodes showed a similar performance. A dependence on the flow
      rate of the sample gas was found in both cases. The sensitivities were higher for
      the ion-exchange membrane-backed electrodes; however, the 3sigma detection limits
      were all in the lower ppb range and for NO were significantly lower on the Nafion
      membrane than on the PTFE membrane. The Nafion electrode was found to show a
      dependence on the relative humidity of the gas stream, but not the PTFE-based
      electrode.

PMID- 11827377
TI  - A selective PVC membrane for di- or trinitrophenol based on N,N-dibenzyl
      3,3',5,5'-tetramethylbenzidine.
AB  - A new fluorophore, N,N-dibenzyl-3,3',5,5'-tetramethylbenzidine (NBTMB), was
      prepared and shown to exhibit significant and analytical usefulness for optical
      sensing toward 2,4-dinitrophenol or 2,4,6-trinitrophenol (picric acid) when it
      was immobilized in a plasticized poly(vinyl chloride) (PVC) membrane. When the
      membrane was applied to aqueous nitrophenol solution, NBTMB was able to extract
      selectively nitrophenol into the membrane phase. Since the extraction equilibrium
      was accompanied by fluorescence quenching of NBTMB, the chemical recognition
      process could be directly translated into an optical signal. The sensor showed
      reversible response in the concentration range from 2.0 x 10(-7) to 6.0 x 10(-5)
      mol L(-1) for the detection of 2,4-dinitrophenol in NaOAc-HOAc buffer at pH 4.0.
      It also showed a fast response time (t95% < 1.5 min) when the sensor was applied
      to 2,4-dinitrophenol solution at concentration levels of 5.26 x 10(-6) and 2.10 x
      10(-5) mol L(-1) alternatively. A working principle is proposed and the responses
      of this sensor to various kinds of nitrophenol were studied. The sensor was
      applied to the direct determination of 2,4-dinitrophenol in prepared water
      samples and the indirect assay of the drug cinchonine and the results obtained
      were satisfactory.

PMID- 11827378
TI  - Effects of electron withdrawing and donating groups on the efficiency of
      tris(2,2'-bipyridyl)ruthenium(II)/tri-n-propylamine electrochemiluminescence.
AB  - The effects of electron withdrawing and electron donating groups on the
      electrochemiluminescent (ECL) properties of tris(2,2'-bipyridyl)ruthenium(II)
      (Ru(bpy)3(2+) where bpy = 2,2'-pyridine) are reported. The electrochemistry,
      photophysics and ECL of (bpy)2Ru(DC-bpy)2+, and (bpy)2Ru(DM-bpy)2+ (DC = 4,4'
      dicarboxy-2,2'-bipyridine; DM = 4,4'-dimethyl-2,2'-bipyridine) have been studied
      relative to Ru(bpy)3(2+) in 50:50 (v/v) acetonitrile(CH3CN):H2O (0.1 M KH2PO4),
      and aqueous solutions. Furthermore, the effects of Triton X-100 (polyethylene
      glycol tert-octylphenyl ether) on the electrochemical, spectroscopic and ECL
      properties of these compounds are reported. The anodic oxidation of Ru(bpy)3(2+),
      (bpy)2Ru(DC-bpy)2+, and (bpy)2Ru(DM-bpy)2+ produces ECL in the presence of tri-n
      propylamine (TPrA) in all solvent systems. ECL efficiencies (phi(ecl), photons
      produced per redox event) of 0.73 and 0.84 for (bpy)2Ru(DC-bpy)2+, and
      (bpy)2Ru(DM-bpy)2+ were obtained in aqueous buffered solution, using Ru(bpy)3(2+)
      as a relative standard (phi(ecl) = 1.0). Addition of 0.4 mM Triton X-100 results
      in a greater than 2-fold increase in ECL efficiences (i.e., 3.8, 2.4 and 2.3 for
      Ru(bpy)3(2+), (bpy)2Ru(DC-bpy)2+, and (bpy)2Ru(DM-bpy)2+, respectively) using
      aqueous Ru(bpy)3(2+) containing no surfactant as standard (phi(ecl) = 1.0). ECL
      efficiencies of 27.4, 16.5 and 26.1 were found in 50:50 (v/v) CH3CN:H2O (0.1 M
      KH2PO4) for Ru(bpy)3(2+), (bpy)2Ru(DC-bpy)2+, and (bpy)2Ru(DM-bpy)2+,
      respectively, using aqueous Ru(bpy)3(2+) containing no surfactant as standard
      (phi(ecl) = 1.0). Detailed studies support adsorption of surfactant on the
      electrode surface, thus facilitating TPrA and ruthenium oxidation.

PMID- 11827379
TI  - Voltammetric determination of niclosamide at a glassy carbon electrode.
AB  - A very sensitive and selective procedure was developed for the determination of
      niclosamide based on square-wave voltammetry at a glassy carbon electrode. Cyclic
      voltammetry was used to investigate the electrochemical reduction of niclosamide
      at a glassy carbon electrode. Niclosamide was first irreversibly reduced from NO2
      to NHOH at -0.659 V in aqueous buffer solution of pH 8.5. Reversible and well
      defined peaks at -0.164 V and -0.195 V (vs. Ag/AgCl) were obtained that are
      responsible for two electron peaks between NHOH and NO. Following optimisation of
      the voltammetric parameters, pH and reproducibility, a linear calibration curve
      over the range 5 x 10(-8)-1 x 10(-6) mol dm(-3) was achieved. The detection limit
      was found to be 2.05 x 10(-8) mol dm(-3) niclosamide. For eight successive
      determinations of 5 x 10(-7) mol dm(-3) niclosamide, a relative standard
      deviation of 2.4% was obtained. This voltammetric method was applied to the
      direct determination of niclosamide in tablets. The results of the analysis
      suggest that the proposed method has promise for the routine determination of
      niclosamide in the products examined.

PMID- 11827380
TI  - PLS regression using real sample calibration for aluminum and iron determination
      in plant extracts.
AB  - Real samples were used for PLS model calibration and validation steps, showing
      that this approach can be of value in preventing deviations in the results caused
      by the matrix effects for the simultaneous spectrophotometric determination of
      aluminum and iron in plant extracts. One hundred UV-vis spectra, obtained from
      samples of the 1997 to 2000 International Plant-Analytical Exchange (IPE) program
      (The Netherlands), were used for model development, with ICP-AES aluminum and
      iron determinations as reference values for model calculation. The plant extracts
      were analyzed both by ICP-AES and by the PLS models developed in this work, using
      calibrations with both aqueous standard solutions and with real sample extracts.
      In addition, since the use of smaller calibration sets could be of value in
      reducing both the cost and the time of analysis, sets with fewer calibration
      samples were also investigated, with the help of the Kennard and Stone algorithm
      for sample selection. Comparison of the predictability of the best model obtained
      with each calibration set was made using the ratio of their relative root mean
      square error (%RMSEV) for samples in the validation set, for aluminum or iron
      determinations, and were compared against F-test tabulated values. For all the
      models developed with real samples, the differences in the %RMSEV values for the
      aluminum or iron determinations were found not to be statistically significant,
      at a confidence level of 95%. Although it was observed that the aluminum, but not
      the iron, determinations with the PLS 2 model prepared with aqueous standards
      tend to be slightly lower than the ICP-AES determinations, this model has a good
      global prediction ability, as observed through the correlation curves presented,
      and can be used for screening determinations or for other agricultural purposes.

PMID- 11827381
TI  - Method optimisation with the use of uncertainty budgets.
AB  - Uncertainty budgets can be used for a variety of situations, e.g. reporting the
      total uncertainty, calculating tolerance limits or method optimisation. In this
      paper it is demonstrated how the use of uncertainty budgets can help in reducing
      the total uncertainty of an analytical method, i.e. method optimisation. In this
      example it has been possible to reduce the total uncertainty of a concentration
      determination of hydrogen peroxide (by titration) from 2.7 x 10(-2) M to 3.93 x
      10(-3) M (or to about a 1/7) by changing the traceability chain and working with
      more pure reagents.

PMID- 11827382
TI  - Quantitative determination of acetylsalicylic acid and acetaminophen in tablets
      by FT-Raman spectroscopy.
AB  - A procedure for quantitative determination of acetylsalicylic acid and
      acetaminophen in pharmaceuticals by PLS (partial least squares) and PCR
      (principal component regression) treatment of FT (Fourier transform)-Raman
      spectroscopic data is proposed. The proposed method was tested on powdered
      samples. Three chemometric models were built: the first, for samples consisting
      of an active substance diluted by lactose, starch and talc; the second, in which
      a simple inorganic salt was applied as an internal standard and additions were
      not taken into account; and the third, in which a model was constructed for a
      commercial pharmaceutical, where all constituents of the tablet were known. By
      utilising selected spectral ranges and by changing the chemometric conditions it
      is possible to carry out fast and precise analysis of the active component
      content in medicines on the basis of the simplified chemometric models. The
      proposed method was tested on five commercial tablets. The results were compared
      with data obtained by intensity ratio and pharmacopoeial methods. To appraise the
      quality of the models, the relative standard error of predictions (RSEPs) were
      calculated for calibration and prediction data sets. These were 0.7-2.0% and 0.8
      2.3%, respectively, for the different PLS models. Application of these models to
      the Raman spectra of commercial tablets containing acetylsalicylic acid gave RSEP
      values of 1.3-2.0% and a mean accuracy of 1.2-1.7% with a standard deviation of
      0.6-1.2%.

PMID- 11827383
TI  - Sensitive measurement of methylene blue active substances by attenuated total
      reflection spectrometry with a trimethylsilane-modified glass slab optical
      waveguide.
AB  - Attenuated total reflection spectrometry with a slab optical waveguide (SOWG) was
      explored for the simple, rapid and sensitive measurement of total anionic
      surfactants by the methylene blue active substance (MBAS) method. A fused-silica
      sheet used as a guiding layer was modified with trimethylsilane (TMS) to extract
      and concentrate the MBASs on the SOWG surface. Based on preliminary studies of
      the adsorption behavior and visible ATR spectrum of MB on the modified silica
      surface, a detection wavelength of 600 nm was chosen for the sensitive
      measurement of anionic surfactants. When the concentration of MB was set at 10
      microM in the final measurement solution, the calibration curve for a typical
      anionic surfactant (sodium dodecylbenzenesulfonate) was linear up to 0.6 microM
      and the detection limit was 0.07 microM. The proposed method was applied to the
      determination of total anionic surfactants in river water.

PMID- 11827385
TI  - Validation of the Willems badge diffusive sampler for nitrogen dioxide
      determinations in occupational environments.
AB  - The Willems badge, a diffusive sampler for nitrogen dioxide, has previously been
      validated for ambient air measurements. This paper describes the laboratory and
      field validation of the Willems badge for personal sampling under working
      environment conditions. The mean sampling rate in the laboratory tests was 46 ml
      min(-1), with an RSD of 12%. No statistically significant effects on sampling
      rate of the sampling time, concentration of NO2 or relative humidity were found.
      A slightly decreased sampling rate was observed at low wind velocity. This was
      also confirmed during static sampling, which makes the sampler less appropriate
      for static sampling indoors. No back diffusion was observed. Storage of the
      samplers for two weeks before or after exposure did not affect the sampling rate.
      Our analysis is based on a modified colorimetric method, performed by FIA (flow
      injection analysis). This technique was compared to ion chromatography analysis.
      The use of ion chromatography lowered the detection limit from 11 to 2 microg m(
      3) for an 8 h sample, and furthermore enabled the detection of other anions. In
      conclusion, the diffusive sampler was found to perform well for personal
      measurements in industrial environments.

PMID- 11827384
TI  - Determination of trace concentrations of hexavalent chromium.
AB  - A simple and sensitive solvent extraction-atomic spectrometric technique has been
      developed for the determination of hexavalent chromium in fresh and saline
      waters. The technique is based on the reaction of chromium with
      diphenylcarbazide. The method has been tested on a variety of water samples over
      an analytical range of 0-2 microg l(-1). A limit of detection of 0.024 microg l(
      1) was achieved. Spiking recoveries in the range 87-115% were achieved in river
      water, drinking water and marine waters.

PMID- 11827387
TI  - Characterisation of heterogeneous solid surfaces by multiple probe, temperature
      programmed inverse gas chromatography (IGC). A feasibility study.
AB  - A method is described for the characterisation of the surfaces of powdered solids
      by temperature programmed, multiple-probe, inverse gas chromatography. This
      modification of "traditional" inverse gas chromatography (IGC) allows rapid
      screening of solid surfaces to compare the adsorptive behaviour of pairs or sets
      of surfaces. This feasibility study examined the criteria for selection of a
      suitable probe set and approaches to the analysis and interpretation of the data
      generated. The technique was used to compare carbon black samples, chosen for
      their surface heterogeneity and the difficulty of surface characterisation using
      other techniques. The choice of a low surface area, methylated silica solid
      diluent and the elimination of its influence on the measurements is discussed.
      The probe set selected readily distinguished the carbon black samples and allowed
      tentative conclusions to be drawn regarding steric and electronic influences on
      probe-solid interactions.

PMID- 11827386
TI  - Comparison of sampling methods for 1,6-hexamethylene diisocyanate, (HDI) in a
      commercial spray box.
AB  - In this study three different types of samplers for the determination of 1,6
      hexamethylene diisocyanate in air were compared. The experimental set up was a
      simulation of real life conditions with spray painting operations performed
      inside a commercial, full sized, spray box. The sampling methods were 1-(2
      methoxyphenyl)-piperazine impregnated on glass fibre filter, and the same reagent
      in impinger, and also dibutylamine in impinger. All analyses were performed by LC
      MS-MS. The determined concentrations varied between 20 and 90 microg m(-3) with
      relative standard deviations from 7 to 17% for each method. No significant
      difference was found between the three methods using ANOVA with a significance
      level of alpha = 0.05.

PMID- 11827388
TI  - Quality control of sampling: proof of concept.
AB  - Quality control in sampling has been demonstrated as practicable in sampling
      procedures that require the combination of sample increments to form a composite
      sample. The proposed method requires no sampling resources or use of time beyond
      those normally used. Increments are allocated at random into two half-sized
      composites, each of which is analysed separately. The absolute difference between
      the two results is plotted on a one-sided control chart, which is interpreted
      like a Shewhart chart. In commonly prevailing circumstances the analytical
      precision is negligible and the chart represents sampling precision alone.

PMID- 11827389
TI  - A new technique to determine organic and inorganic acid contamination.
AB  - A new acid indicator pad was developed for the detection of acid breakthrough of
      gloves and chemical protective clothing. The pad carries a reagent which responds
      to acid contaminant by producing a color change. The pad was used to detect both
      organic and inorganic acids permeating through glove materials using the modified
      ASTM F-739 and direct permeability testing procedures. Breakthrough times for
      each type of glove were determined, and found to range from 4 min to > 4 h for
      propionic acid, from 3 min to > 4 h for acrylic acid, and from 26 min to > 4 h
      for HCl. A quantification was performed for propionic and acrylic acids following
      solvent desorption and gas chromatography. Both acids exhibited > 99% adsorption
      [the acid and its reactivity (the acid reacted with an indicator to contribute
      the color change)] on the pads at a spiking level of 1.8 microL for each acid.
      Acid recovery during quantification was calculated for each acid, ranging from 52
      72% (RSD < or = 4.0%) for both acids over the spiking range 0.2-1.8 microL. The
      quantitative mass of the acids on the pads at the time of breakthrough detection
      ranged from 260-282 and 270-296 microg cm(-2) for propionic acid and acrylic
      acid, respectively. The new colorimetric indicator pad should be useful in
      detecting and collecting acid permeation samples through gloves and chemical
      protective clothing in both laboratory and field studies, for quantitative
      analysis.

PMID- 11827390
TI  - Methods for testing antioxidant activity.
AB  - Antioxidant activity has been assessed in many ways. The limitation of many newer
      methods is the frequent lack of an actual substrate in the procedure. The
      combination of all approaches with the many test methods available explains the
      large variety of ways in which results of antioxidant testing are reported. The
      measurement of antioxidant activities, especially of antioxidants that are
      mixtures, multifunctional or are acting in complex multiphase systems, cannot be
      evaluated satisfactorily by a simple antioxidant test without due regard to the
      many variables influencing the results. Several test procedures may be required
      to evaluate such antioxidant activities. A general method of reporting
      antioxidant activity independent of the test procedure is proposed.

PMID- 11827391
TI  - Molecularly imprinted CEC sorbents: investigations into polymer preparation and
      electrolyte composition.
AB  - The influence of the sorbent preparation protocol and separation parameters on
      the selectivity and chromatographic efficiency of super-porous molecularly
      imprinted polymer (MIP) monoliths in capillary electrochromatography (CEC) was
      studied. Chiral templates were employed and enantiomer separation and resolution
      were used as measures of imprint selectivity and column efficiency, respectively;
      the latter was in addition studied by chromatography of non-related aromatic
      structures. The polymer preparation was varied with respect to monomer
      composition in the pre-polymerisation mixture and also the use of single versus
      multiple template(s). The separation parameters investigated were type and
      content of organic solvent and surfactant modifier in the electrolyte. It was
      found that acetone and acetonitrile in buffer mixtures provided enantiomer
      separation of enantiomers of the template and also structural analogues; however,
      the degree of separation was greatly influenced by the content in the
      electrolyte. Three surfactants, sodium dodecylsulfate (SDS),
      cetyltrimethylammonium bromide (CTAB) and polyoxyethylene sorbitanmonolaurate
      (Tween 20), were examined as electrolyte modifiers. It was found that addition of
      SDS decreased and CTAB and Tween 20 increased the enantiomer separation. SDS and
      CTAB could be used up to 1 mM concentration whereas Tween could be used up to 90
      mM concentration without causing baseline disturbances. The effects found and
      demonstrated strongly suggest that these parameters are to be considered during
      optimisation of an MIP-CEC system.

PMID- 11827392
TI  - Determination of furosemide in urine samples by direct injection in a micellar
      liquid chromatographic system.
AB  - A sensitive, selective and efficient micellar liquid chromatographic (MLC)
      procedure was developed for the determination of furosemide (4-chloro-N-furfuryl
      5-sulfamoylanthranilic acid) in urine samples by direct injection and UV
      detection. The procedure makes use of a C18 reversed-phase column and a micellar
      mobile phase of 0.05 mol l(-1) sodium dodecyl sulfate-6% v/v propanol and
      phosphate buffer at pH 3 to resolve furosemide from its photochemical degradation
      products. The importance of protecting the standards and urine samples to be
      analysed from light in the assay of furosemide, avoiding its degradation, was
      verified. The limit of quantification was 0.15 microg ml(-1) and the relative
      standard deviation of the inter-day assay was 0.8-0.04% in the 6-82 microg ml(-1)
      range. Detection of urinary excretion of furosemide was followed up to 12 h after
      ingestion of the drug by a healthy volunteer. No potential interference from the
      major metabolite (furosemide acylglucuronide) and its hydrolytic product (4
      chloro-5-sulfamoylanthranilic acid) was observed. Commonly administered drugs
      also did not interfere. The proposed MLC procedure permits the rapid and
      reproducible measurement of low levels of furosemide in a small amount of urine.

PMID- 11827393
TI  - Mechanism of response enhancement in evaporative light scattering detection with
      the addition of triethylamine and formic acid.
AB  - Triethylamine with an equimolar amount of formic acid added to the mobile phase
      provides an enhancement of the evaporative light scattering detector (ELSD)
      response. After characterization of the influence of various parameters on the
      ELSD response, a sequential strategy was defined to elucidate this response
      enhancement. The response enhancement was more marked at low mobile phase flow
      rate, and was highly dependent on solutes and solvents. The influence of drift
      tube temperature on response enhancement with various solutes demonstrated that
      triethylamine and formic acid mainly act as mass amplifiers by the inclusion of
      triethylamine-formic acid clusters inside the droplets.

PMID- 11827394
TI  - Solid-phase microextraction as a sample preparation strategy for the analysis of
      seleno amino acids by gas chromatography-inductively coupled plasma mass
      spectrometry.
AB  - Solid-phase microextraction (SPME) is used as a sample preparation strategy for
      gas chromatographic (GC) analysis of the seleno amino acids, selenomethionine
      (SeMet), selenoethionine (SeEt) and selenocystine (SeCys). Acylation of the amino
      group and esterification of the carboxylic group in these compounds was performed
      with isobutylchloroformate to increase volatility. The amino acid derivatives
      were then extracted by silica fibers with polydimethylsiloxane (PDMS) coatings
      prepared by the sol-gel process. Investigations of extraction time, acid and salt
      addition, and polymer length (for the sol-gel process) were conducted with the
      goal of procedural optimization. Initial characterizations were conducted using
      gas chromatography with flame ionization detection (GC-FID). Inductively coupled
      plasma mass spectrometric detection was employed for final selenium detection.
      Sub-ppb detection limits were obtained for all analytes although relative
      standard deviations were higher than those typically obtained in solid-phase
      microextraction.

PMID- 11827395
TI  - A disposable amperometric biosensor for rapid screening of anticholinesterase
      activity in soil extracts.
AB  - A disposable amperometric biosensor for the determination of anticholinesterase
      activity in soil extracts is described. The sensitive membrane was obtained by co
      crosslinking acetylcholinesterase and choline oxidase with bovine serum albumin
      using glutaraldehyde. The anticholinesterase activity of the soil extract was
      measured using chronoamperometry at 650 mV vs. Ag/AgCl to monitor the
      biocatalytically produced H2O2 before and after the inhibition step. An
      inhibition percentage of 38 +/- 4% was recorded for soil extracts spiked with 10
      ppb of ethyl parathion. The device has the potential to be used as a gross sensor
      for the assessment of anticholinesterase activity in soil extracts.

PMID- 11827396
TI  - An automated analyzer for methylated arginines in rat plasma by high-performance
      liquid chromatography with post-column fluorescence reaction.
AB  - A fully automated analyzer for methylated L-arginine metabolites [N,N-dimethyl-L
      arginine (ADMA), N-methylarginine (NMMA) and N,N'-dimethyl-L-arginine (SDMA)] by
      high-performance liquid chromatography with post-column fluorescence
      derivatization was developed. This system consists of an on-line extraction, a
      separation on a reversed phase ion-pair chromatograph, a post-column
      derivatization by o-phthaladehyde (OPA) and thiol reaction, and fluorescence
      detection. NMMA, ADMA and SDMA were separated in 40 min with isocratic elution by
      a combination of octanoate and cyclohexane carboxylate as ion-pair reagents. The
      eluate was monitored at 450 nm with excitation at 337 nm. The calibration curves
      for NMMA, ADMA and SDMA showed linearity over the range from 0.05 micromol l(-1)
      (0.5 pmol on column) to 5.0 micromol l(-1) (50 pmol on column). This method does
      not require any time-consuming pre-treatment and requires only 10 microl of
      plasma sample for assay.

PMID- 11827397
TI  - Determination of an arsenosugar in oyster extracts by liquid chromatography
      electrospray mass spectrometry and liquid chromatography-ultraviolet photo
      oxidation-hydride generation atomic fluorescence spectrometry.
AB  - HPLC-UV-HG-AFS analysis of aqueous extracts of oysters (Crassostrea gigas) taken
      from the southwestern Atlantic coast of Spain showed the presence of arsenite,
      arsenate, dimethylarsinic acid and an unidentified arsenic peak. Subsequent
      analysis of the oyster samples by LC-electrospray MS and comparison with four
      standard dimethylarsinoylribosides (arsenosugars), showed that the previously
      unidentified peak was an arsenosugar (arsenosugar 2). When the arsenosugar in the
      oyster was quantified using the two detection methods and external calibration
      with standard arsenosugar, there was a large discrepancy between the two sets of
      results. The LC-MS analysis was strongly affected by the sample matrix and gave
      concentrations 50% lower than those obtained by AFS detection. When the method of
      standard addition was applied to the LC-MS analysis, the results were comparable
      to the AFS data. The matrix effects were eliminated by subjecting the extract to
      a clean-up procedure with anion-exchange and gel permeation preparative
      chromatography before the LC-MS analysis. The arsenosugars gave a small signal
      without photo-oxidation when they were analysed by HPLC-HG-AFS. Possibly this
      resulted from partial decomposition of the arsenosugar to dimethylarsinic acid
      under the acidic conditions employed in the hydride generation step.

PMID- 11827398
TI  - Rapid determination of underivatized pyroglutamic acid, glutamic acid, glutamine
      and other relevant amino acids in fermentation media by LC-MS-MS.
AB  - Determination of amino acids in a complex matrix without derivatization is
      advantageous, however, difficulties are found in both the detection and the
      separation of those compounds. In this study, a rapid and reliable LC-MS-MS
      method for the quantitation of underivatized amino acids in exocellular media was
      established. Injections were made directly after centrifugation of the samples,
      without further preparation. The separation of seven underivatized amino acids
      was achieved on a reversed-phase C18 column with pentadecafluorooctanoic acid as
      a volatile ion-pair reagent, and the specific detection of most amino acids was
      achieved by MS-MS of the specific transitions [M + H]+-->[M + H - 46]+. The
      calibration curves of all analytes were linear over the range of 1.0-1000 microg
      ml(-1) and the detection limits ranged from 0.1 to 5 ng ml(-1), with an injection
      volume of 20 microl. The inter-day and intra-day precisions ranged from 2.6 to
      5.7% and 4.8 to 8.2%, respectively; the mean recoveries of the seven analytes
      were 81-104%, 91-107% and 93-101% respectively at the spiked level of 10, 40 and
      200 microg ml(-1). A large number of fermentation samples were analysed using
      this method. The technique is simple, rapid, selective and sensitive, and shows
      potential for the high-throughput quantitation of amino acids from other
      biological matrices.

PMID- 11827399
TI  - Comparison of two ICP-MS set-ups for measuring 99Tc in large volume water
      samples.
AB  - Large volume fjord and seawater samples have been radiochemically prepared for
      ICP-MS analysis in order to test the robustness of the procedure and to carry out
      a comparison of two ICP-MS set-ups. A sector field instrument (MicroMass PT2)
      coupled with an ultrasonic nebuliser and a quadrupole ICP-MS (Perkin-Elmer Elan
      6000) coupled with an electrothermal vaporisation (ETV) unit were used. The
      results showed that the radiochemical procedure was robust, removing Ru and Mo to
      acceptable levels, and that the two set-ups gave results that were in agreement.
      The correlation coefficient between the sets of 11 results was 1.0 +/- 0.05. The
      importance of establishing the matrix effect when using an ETV is discussed.

PMID- 11827400
TI  - Multielemental analysis of Mn-Fe nodules by ICP-MS: optimisation of analytical
      method.
AB  - Two acid digestion procedures (microwave-assisted and room temperature) were
      developed for the quantitative analysis of ferromanganese nodules by inductively
      coupled plasma double focusing sector field mass spectrometry (ICP-SFMS).
      Different compositions of the acid mixture, dilution factors and corrections for
      spectral interferences were tested. A combination of nitric, hydrochloric and
      hydrofluoric acids is necessary for complete sample digestion, with lowest acid
      to sample ratios (v/m) of 15 and 1.5, respectively, for the last two acids.
      Sample dilution factors higher than 2 x 10(4) should be used in order to decrease
      matrix effects and provide robust long-term instrumental operation. In spite of
      high dilution, method detection limits in the sub-microg g(-1) range were
      obtained for 54 out of 71 elements tested, due to the high detection capability
      of ICP-SFMS, as well as the special care taken to ensure the purity of reagents,
      to clean the instrument sample introduction system and to minimise sample
      handling. Owing to the presence of unresolved (at the resolution available)
      spectral interferences, accurate determination of Au, Hg, Os, Pd, Re and Rh is
      impossible without matrix separation. The accuracy of the entire analytical
      method was tested by the analysis of two nodule reference materials. The results
      generated agreed to within +/-2% for about 10, within +/-10% for more than 40 and
      within +/-20% for about 50 of 53 elements for which certified, recommended or
      literature values are available. A precision better than 3%, expressed as the
      between-digestion relative standard deviation (n = 4), was obtained for the
      majority of elements, except in cases limited by low analyte concentrations.

PMID- 11827401
TI  - Ultrasonic extraction of iron from non-aqueous liquids.
AB  - A novel procedure for the extraction of iron from predominately organic solvents
      has been described. An ultrasonic probe was used to create a microemulsion with a
      small quantity of nitric acid such that labile iron could be released into the
      aqueous vesicles and subsequently quantified after phase separation. The
      analytical and operational viability of using a simple colorimetric assay based
      on the coordination of aminothiol ligands (principally homocysteine) was
      evaluated in terms of signal sensitivity, selectivity and stability. The use of
      homocysteine provided a linear range for iron(III) from 9 microM to 50 microM
      with a corresponding limit of detection of 2 microM (based on 3s(b)). The
      effectiveness of the approach was assessed through the recovery of 0.3 ppm iron
      from a sample of commercial kerosene and the results compared with those obtained
      through attempting to quantify the iron under passive (ultrasonically silent)
      conditions.

PMID- 11827402
TI  - A specificity-enhanced time-resolved fluoroimmunoassay for zeranol employing the
      dry reagent all-in-one-well principle.
AB  - A simple dry chemistry time-resolved fluorescence immunoassay (TR-FIA) method was
      developed for the measurement of zeranol in bovine urine samples. The samples
      were purified by immunoaffinity chromatography and a specificity-enhanced zeranol
      antibody was employed in the immunoassay. This resulted in a highly selective
      method, which had only negligible reactivity with Fusarium spp. toxins. The all
      in-one-well dry chemistry concept made the assay very simple to use because all
      the assay-specific reagents were already present in the reaction wells in dry
      form. Only the addition of diluted sample extract was required to perform the
      competitive one-step TR-FIA and the results were available in less than 1 h. The
      analytical limit of detection (mean + 3s) for the immunoassay was 0.16 ng ml(-1)
      (n = 12) and the functional limit of detection for the whole method, estimated by
      the analysis of zeranol-free samples, was 1.3 ng ml(-1) (n = 20). The recovery of
      zeranol at the level of 2 ng ml(-1) was 99% (n = 18) and the within-assay
      variation ranged between 4.5 and 9.0%.

PMID- 11827403
TI  - Immunofiltration as sample cleanup for the immunochemical detection of beta
      agonists in urine.
AB  - Despite the ban of the European Union on use of drugs to improve animal growth,
      occasionally beta-agonist drugs are still found in samples from cattle. Over
      time, the specified limits for the detection of these illegal drugs have been
      lowered. To improve the immunochemical screening of urine samples to detect lower
      levels of several beta-agonists, immunofiltration (IF) was applied for sample
      cleanup in combination with a beta-agonist-ELISA. In the applied IF format, free
      (non-immobilised) anti-salbutamol polyclonal antibodies were mixed with the urine
      sample in an ultra-filtration device (cut off 30 kDa) and the sample was removed
      by centrifugation. The antibody bound beta-agonists were freed from the
      antibodies by the addition of a mixture of methanol and 0.1 M acetic acid (1:1;
      v/v) and centrifugation. The filtrate, containing the free beta-agonists, was
      evaporated to dryness and the residue dissolved in buffer, an aliquot of which
      was analysed with the beta-agonist ELISA. Compared with the direct beta-agonist
      ELISA, this IF cleanup procedure resulted in a 30-times lower limit of detection
      (LOD) of 0.14 ng ml(-1) (salbutamol equivalents). The anti-salbutamol antibodies
      recognised several beta-agonists and the combination of IF with the beta-agonist
      ELISA was found suitable for the detection of at least ten beta-agonists in urine
      with comparable LODs.

PMID- 11827404
TI  - Development of a highly sensitive enzyme-linked immunosorbent assay for bisphenol
      A in serum.
AB  - 4,4'-Isopropylidenediphenol, bisphenol A (BPA), was derivatized to BPA
      carboxymethylether (BPA-CME), BPA-carboxypropylether (BPA-CPE) and BPA
      carboxybutylether (BPA-CBE), and then linked to bovine serum albumin (BSA). The
      BPA-BSA conjugates were injected into female New Zealand White rabbits, which
      then generated six kinds of polyclonal antibodies. In addition, BPA and bisphenol
      B (BPB)-enzyme conjugates were derivatized to BPA-CME, BPA-CPE, BPA-CBE, BPA
      carboxyphenylether (CPhE) and BPB-CPE, and then linked to horseradish peroxidase
      (HRP). An enzyme-linked immunosorbent assay (ELISA) was developed and the
      specificity of the antibodies was confirmed by comparison with pre-immune serum
      and by competitive assays using different dilutions of BPA standards. Although
      anti-BPA antibodies cross-reacted with BPB by more than 13.6% at all dilutions
      used, cross-reaction with phthalates and phenols occurred only less than 0.1%.
      The combination with the highest sensitivity was obtained using anti-BPA-CME-BSA
      antibody and BPA-CPhE-HRP conjugate. ELISA successfully detected BPA in human
      serum at concentrations as low as 0.3 ng mL(-1), and over a measurable range of
      0.3-100 ng mL(-1). Recovery tests were carried out by adding BPA to three kinds
      of human serum, and ranged from 89.7 to 97.3%, from 85.4 to 94.9% and from 81.9
      to 97.4%, respectively. The correlation between the results from ELISA and gas
      chromatography-mass spectrometry (GC-MS) for BPA in spiked serum was r2 = 0.990,
      indicating that the proposed method is a potential tool for screening a large
      number of human serum samples.

PMID- 11827405
TI  - Monoclonal-based enzyme-linked immunosorbent assay and immunochromatographic
      assay for enrofloxacin in biological matrices.
AB  - Enrofloxacin has been increasingly used in veterinary medicine to treat microbial
      infections. A simple and reliable analytical method for this drug is required.
      The current determination by high performance liquid chromatography (HPLC) is
      sensitive but labor-intensive. This paper reports an enzyme-linked immunosorbent
      assay (ELISA) using a monoclonal antibody (MAb) and the development of a rapid
      test kit based on immunochromatography. The detection limits using the ELISA were
      10 ppb for chicken liver and muscle, and 1 ppb for cattle milk, respectively. The
      mean recovery values were 77.3-96.0% for chicken liver, 72.4-92.0% for chicken
      muscle and 84.0-99.0% for cattle milk. The detection limits using the kit were
      ca. 100 ppb for chicken muscle and ca. 10 ppb for cattle milk, respectively. All
      ELISA results for assay of chicken liver, chicken muscle and cattle milk were
      confirmed using HPLC which is used as the routine assay. The HPLC (x) and ELISA
      (y) results showed close correlation for chicken liver (y = 8.7 + 0.85x, r2 =
      0.99, n = 25), chicken muscle (y = -3.9 + 0.94x, r2 = 0.98, n = 25) and cattle
      milk (y = 18.4 + 0.92x, r2 = 0.99, n = 25).

PMID- 11827406
TI  - Editorial: breast pathology.

PMID- 11827407
TI  - HER2 testing recommendations in Australia.
AB  - HER2 is the target of a new treatment for metastatic breast cancer using the
      humanised monoclonal antibody trastuzumab (Herceptin). Since only around 20% of
      breast cancers carry the overexpressed HER2 receptor protein to which this
      treatment is directed, patient selection is very important in determining
      eligibility for the drug. Currently, immunohistochemistry and fluorescence in
      situ hybridisation are the main tests used for HER2 detection, and these testing
      recommendations have been developed based on national and international data.

PMID- 11827408
TI  - False-positive reports in fine needle biopsy of breast lesions.
AB  - A review of the literature reveals considerable variations in the diagnostic
      accuracy of fine needle biopsy (FNB) of breast lesions between series, partly due
      to different methods of calculation, different definitions, and insufficient
      numbers of cases with adequate follow-up to provide reliable statistics. The best
      larger series have a false-positive rate between 0.2 and 0.3%, slightly higher
      for non-palpable than for palpable lesions. The cytological patterns of a range
      of benign lesions which may cause diagnostic difficulties and may be misdiagnosed
      as malignant by FNB are described, and guidelines to reduce the risk of false
      positive diagnoses are proposed.

PMID- 11827409
TI  - Can phyllodes tumours of the breast be distinguished from fibroadenomas using
      fine needle aspiration cytology?
AB  - In an attempt to determine whether it is possible to distinguish phyllodes
      tumours (PTs) of the breast from fibroadenomas (FAs) using fine needle aspiration
      cytology (FNAC), we reviewed the cytological slides of eight histopathologically
      confirmed PTs (six benign and two malignant) and compared them with cytological
      features of 13 histopathologically confirmed FAs. Each author independently,
      "blindly" assessed architectural and cytological features of the stromal (six
      features) and epithelial (seven features) components and the cytological
      background (three features) and gave a favoured diagnosis for each case. Four of
      six benign PTs, one of two malignant PTs and 11 of 13 FAs were correctly
      diagnosed cytopathologically by at least three of the authors. The presence of
      hypercellular stromal fragments was the most useful feature in distinguishing PTs
      from FAs, and the presence of cytological atypia of the stromal cells was the
      most important feature in distinguishing malignant from benign PTs. Sampling
      error was the most common reason for cytological misdiagnosis of PTs. The two FAs
      misdiagnosed as PTs were each of cellular type. The results of this study suggest
      that it is possible to distinguish PTs from FAs using FNAC in most cases. We
      recommend that if hypercellular stromal fragments are identified in a FNAC
      specimen of a fibroepithelial lesion, the cytopathologist should raise the
      possibility of a PT and the surgeon treat the patient accordingly.

PMID- 11827410
TI  - Histological correlation of mammographically detected microcalcifications in
      stereotactic core biopsies.
AB  - The aims of this study were to assess the value of specimen radiographs of
      stereotactic core biopsy, the usefulness of measuring size of calcifications on
      tissue sections, whether demonstration of calcifications in tissue sections
      alters the pathological diagnosis when specimen radiograph demonstrates
      calcifications, and to correlate these assessments with diagnostic outcome. A
      total of 301 core biopsies from 266 women with 274 mammographically suspicious
      areas of calcifications were examined. Core biopsies (five cores per procedure)
      were obtained stereotactically using a 14-gauge needle in an automated Biopty
      gun. Prior to processing of the tissue, 214 core biopsy specimens from 193 women
      with 197 lesions were radiographed. Of the 301 core biopsies, 56 (19%) were
      diagnosed as malignant, 15 (5%) were diagnosed as atypical ductal hyperplasia and
      230 (76%) contained benign breast tissue. Of the core biopsies diagnosed as
      benign, 160 (70%) had specimen radiography prior to processing. Of these, 109
      (69%) core biopsies showed calcifications on specimen radiographs. In 96 (88%) of
      these core biopsies, calcifications measuring > 100 microm were found on the
      initial tissue sections. In 11 (10%) further deeper sections were required to
      detect calcifications > 100 microm; however, this did not result in a change of
      the pathological diagnosis. Two of the 109 (1.8%) "benign" core biopsies, which
      contained tissue calcifications > 100 microm and at that time were considered
      representative of the mammographic lesion, have had a malignant outcome on
      clinical and mammographic follow-up ranging from 2.4 to 7.5 years. Of the 51
      (31%) core biopsies where calcifications were not seen on specimen radiographs,
      histological calcifications were not found in 34 (67%) core biopsies, whereas in
      17 (33%) core biopsies, calcifications measuring < 100 microm were found. All of
      these core biopsies were considered non-diagnostic and therefore not
      representative of the lesion targeted. Five (9.8%) of these cases had a malignant
      outcome with either immediate rebiopsy or excision. Accurate diagnosis of all
      mammographic lesions requires radiological-pathological correlation. This study
      shows that the presence of calcifications on the specimen radiograph and the
      demonstration of tissue calcifications > 100 microm are an essential and highly
      reliable part of core biopsy assessment for mammographically "suspicious"
      calcifications. Nevertheless, lesions with "highly suspicious" calcifications on
      mammography should be considered for excision even if the core biopsy diagnosis
      is benign and calcifications > 100 microm are present.

PMID- 11827411
TI  - Diagnosis of breast microcalcifications: a comparison of stereotactic FNA and
      core imprint cytology as adjuncts to core biopsy.
AB  - Stereotactic core biopsy (CB) using 14-gauge needles was adopted as the standard
      method of diagnosis of screen-detected breast microcalcifications (MC) at Sir
      Charles Gairdner Hospital in 1996. Fine needle aspiration (SFNA) was included as
      an adjunct, to optimise sensitivity and to provide immediate reporting. Recently,
      core imprint cytology (CI) has been shown to have a high sensitivity in
      diagnosing malignancy. The aims of this paper were to evaluate the accuracy of
      SFNA as an adjunct to CB, and whether CI could replace SFNA for immediate
      reporting in MC. Part A is a retrospective review of CB/SFNA of screen-detected
      MC from May 1998 to February 2000. A minimum of five cores was performed. SFNA
      samples were restricted to a maximum of three needle passes. Part B is a
      prospective study of CI from May to November 2000. In Part A, there were 406 MC
      in 353 women and 81 carcinomas were proven on excision. The complete sensitivity
      of CB for a diagnosis of malignancy was 97.5% and of SFNA was 65%. No false
      positive diagnoses were made by either method. No extra carcinomas were detected
      using SFNA. In Part B, CB/CI were performed on 203 MC from 165 women. There were
      38 carcinomas and 30 of these (79%) were diagnosed as malignant on CI. No false
      positive diagnoses were made. The predictive value of a benign diagnosis was 95%.
      SFNA had little value as an adjunct to core biopsy in MC. CI promises to be
      useful in providing same day diagnosis for counselling purposes and for planning
      future surgery.

PMID- 11827412
TI  - Effect of transforming growth factor-beta1, insulin-like growth factor-I and
      insulin-like growth factor-II on cell growth and oestrogen metabolism in human
      breast cancer cell lines.
AB  - Oestrogens play an important role in the development of breast cancer. Oestrone
      sulphate (E1S) acts as a huge reservoir of oestrogens in the breast and is
      converted to oestrone (E1) by oestrone sulphatase (E1STS). E1 is then reversibly
      converted to the potent oestrogen, oestradiol (E2) by oestradiol-17beta
      hydroxysteroid dehydrogenase (E2DH). The aim of this study was to assess the
      effects of transforming growth factor-beta1 (TGFbeta1), insulin-like growth
      factor-I (IGF-I) and insulin-like growth factor-II (IGF-II) on cell growth, E1STS
      and E2DH activities in the MCF-7 and MDA-MB-231 human breast cancer cell lines.
      TGFbeta1, IGF-I and IGF-II alone or in combination inhibited cell growth of both
      cell lines but no additive or synergistic effects were observed. The treatments
      significantly stimulated E1STS activity in the MCF-7 cell line, except for
      TGFbeta1 alone and TGFbeta1 and IGF-I in combination, where no effects were seen.
      Only TGFbeta1 and IGF-II acted synergistically to stimulate E1STS activity in the
      MCF-7 cells. There was no significant effect on E1STS activity in the MDA-MB-231
      cells with any of the treatments. In the MCF-7 cells, TGFbeta1 and IGF-I, IGF-I
      and IGF-II, and TGFbeta1, IGF-I and IGF-II acted synergistically to stimulate the
      reductive E2DH activity, while only TGFbeta1, IGF-I and IGF-II synergistically
      stimulated the oxidative E2DH activity. There were no additive or synergistic
      effects on both oxidative and reductive E2DH activities in the MDA-MB-231 cells.
      In conclusion, TGFbeta1, IGF-I and IGF-II may have effects on oestrogen
      metabolism, especially in the MCF-7 cell line where they stimulated the
      conversion of E1S to E1 and E1 to E2 and, thus, may have roles to play in the
      development of breast cancer.

PMID- 11827413
TI  - The emerging role of the human herpesvirus 8 (HHV8) in human neoplasia.
AB  - The human herpesvirus 8 (HHV8) was initially described and characterised in
      Kaposi's sarcoma tissue. The virus was found in the lesion of most cases of
      Kaposi's sarcoma. Whilst there is a large body of evidence to implicate its role
      in the pathogenesis of Kaposi's sarcoma, it has recently been found that the
      virus may also be important in a number of other human neoplasias. This review
      will examine the molecular pathology of HHV8 in the pathogenesis of Kaposi's
      sarcoma and summarise the current evidence and postulated mechanisms in its role
      in other human neoplasias.

PMID- 11827414
TI  - Expression of cyclooxygenase-1 and -2 in urinary bladder carcinomas in vivo and
      in vitro and prostaglandin E2 synthesis in cultured bladder cancer cells.
AB  - Cyclooxygenases (Coxs) are the rate-limiting enzymes catalysing the formation of
      prostaglandins, which are involved in various of physiological processes.
      Increased Cox-2 expression has been observed in several malignancies, but the
      exact role of Cox-2 in carcinogenesis remains unsolved. We studied the expression
      of both Cox-1 and Cox-2 by immunohistochemistry in 29 transitional cell
      carcinomas of the urinary bladder. Diffuse cytoplasmic immunosignal for Cox-2 was
      detected in all cancer specimens. The expression was moderate in 55% and strong
      in 31% of the carcinomas. The normal urothelium in the samples stained also for
      Cox-2, but the intensity of the immunosignal was weak in most specimens. Cox-1
      was expressed in the stroma of bladder wall, whereas in the tumour cells, Cox-1
      immunosignal was either absent or weak. No correlation was detected between Cox-1
      or Cox-2 expression and tumour differentiation or stage of invasion. We also
      evaluated the mRNA expression of Cox-1 and Cox-2 and synthesis of prostaglandin
      E2 (PGE2) in three bladder carcinoma cell lines (RT4, 5637, and T24). All cell
      lines expressed high levels of Cox-2 mRNA, whereas Cox-1 mRNA expression was
      detected only in T24 cells. There was great variation in the basal levels of PGE2
      synthesis in these cell lines. Indomethacin inhibited the synthesis of PGE2 in
      all three cell lines, although the level of Cox-2 mRNA tended to increase by
      indomethacin. These results indicate that Cox-2 is widely expressed in human
      bladder carcinomas and that the role of Cox-2 inhibition in bladder cancer should
      be further studied.

PMID- 11827415
TI  - The pathology of human and murine pulmonary infection with Cryptococcus
      neoformans var. gattii.
AB  - Human infection by Cryptococcus neoformans var. neoformans is well characterised
      and usually occurs in immunocompromised patients. Less is known about infection
      by Cryptococcus neoformans var. gattii, which usually produces disease in
      previously normal individuals. In two cases of human pulmonary infection by
      Cryptococcus neoformans var. gattii, we observed a mixed inflammatory pattern,
      including granulomas associated with numerous T lymphocytes and a lymphocytic
      interstitial pneumonitis with B lymphocytes and formation of follicles. We also
      established a murine model of pulmonary infection by Cryptococcus neoformans var.
      gattii, which reproduced most of these features. This model is likely to prove
      useful in studies of the pathogenesis of this infection.

PMID- 11827416
TI  - Dendritic cells and their emerging clinical applications.
AB  - Dendritic cells (DC) are now recognised as a unique leukocyte type, consisting of
      two or more subsets. The origins and functional inter-relationships of these
      cells are the subject of intense basic scientific investigation. They play
      important roles in initiating and directing immune responses, defending the host
      from pathogens and maintaining self tolerance. Fundamental studies are defining
      new molecules and mechanisms associated with DC function. The first methods for
      counting these rare blood cell populations are already providing interesting new
      clinical data. Indeed, abnormal DC function may contribute to deficiencies in the
      immune response against malignancies. Phase I trial data suggests that DC-based
      cancer vaccination protocols may contribute an important new biological approach
      to cancer therapy. Manipulation of DC to facilitate allogeneic transplantation
      and even to manage autoimmune disease are likely developments.

PMID- 11827417
TI  - Evaluation of the MRSA-Screen Test in detecting oxacillin resistance in community
      and hospital isolates of Staphylococcus aureus.
AB  - The MRSA-Screen Test (Denka Seiken Co., Japan), a latex agglutination test to
      detect penicillin-binding protein 2a, was compared with PCR for the detection of
      oxacillin resistance in Staphylococcus aureus. A total of 77 oxacillin-sensitive
      and 269 oxacillin-resistant (ORSA) isolates were evaluated. Of the ORSA isolates,
      186 were non-multiresistant (NORSA), defined as being resistant to two or fewer
      antibiotics other than beta-lactams. Eighty-three were multiresistant ORSA
      (MORSA) strains. If PCR is considered the gold standard test, then the
      sensitivity, specificity, positive and negative predictive values of the MRSA
      Screen Test were 100, 99, 99 and 100%, respectively. The endpoint was hard to
      read with NORSA strains that took longer than 60 s to react. MORSA strains took a
      median 12 s (range 5-60 s) to give a positive reaction with the MRSA-Screen Test,
      whereas NORSA strains took a median 30 s (range 5-180 s), a difference which was
      significantly different (P < 0.0001, two-tailed Mann-Whitney unpaired two sample
      test). NORSA strains had an MIC50 of 128 mg/l and MIC90 of 256mg/l, whereas MORSA
      strains had an MIC50 and MIC90 of >256mg/l. The time that the MRSA-Screen Test
      took to agglutinate with ORSA strains correlated weakly with the MIC (r2 = 0.26).
      Detection of methicillin resistance cost AUD$9 per isolate with the MRSA-Screen
      Test, compared with AUD$13 per isolate with mecA PCR. The MRSA-Screen Test gave
      excellent sensitivity and specificity, and was quicker and cheaper than PCR. The
      full 3 min should be allowed to elapse before calling a test negative. Organisms
      giving indeterminate reactions should be tested for the mecA gene by PCR.

PMID- 11827418
TI  - Detection of Helicobacter pylori antigen in faeces by enzyme immunoassay.
AB  - The detection of Helicobacter pylori antigen directly in faecal specimens may
      offer an alternative non-invasive method for determining the presence of H.
      pylori infection. This study compared the performance of the Premier Platinum
      HpSA enzyme immunoassay (HpSA) with histology and CLOtest, a rapid urease test.
      Of 134 patients undergoing upper gastrointestinal endoscopy, 37 (28%) were H.
      pylori-positive by histology and CLOtest. Using the HpSA test, H. pylori was
      detected in 35 H. pylori-positive patients (95% sensitivity) and one H. pylori
      negative patient (99% specificity). The positive and negative predictive values
      for HpSA were 97 and 98%, respectively. HpSA is a rapid, easily performed, non
      invasive method for detecting H. pylori.

PMID- 11827419
TI  - Practical applications of Internet resources for cost-effective telepathology
      practice.
AB  - Telepathology is the interpretation of digital microscopy images on a computer
      monitor at a significant distance from the location of original histology slides.
      Its use has proliferated globally and is part of routine practice in many
      laboratories. Even so, many perceive telepathology as requiring heavy initial
      capital expenditure. However, telepathology may be implemented in a wide variety
      of ways, some inexpensive. The limiting factor is often the technical knowledge
      and skill of the pathologist, not the technology or economics. The Internet is a
      versatile medium that may act as a repository of information in telepathology or
      as a communication conduit for either real-time (dynamic or robotic) or store-and
      forward (static) methods. PubMed is an excellent starting point for literature
      research, with many journals providing full versions of their articles online to
      subscribers. However, these are largely in other fields of medicine and good
      online resources dedicated to telepathology techniques and information are less
      easily found. As a conduit for communication, the Internet can be the most
      economical option. Nearly every form of telepathology may use the Internet,
      provided there is sufficient bandwidth. Several techniques applied to general
      imaging may be used in store-and-forward telepathology. This article outlines
      some examples and discusses their relative merits.

PMID- 11827420
TI  - Test and teach. Unusual pulmonary vascular pathology in a young dyspnoeic woman.
      Pulmonary tumour thrombotic microangiopathy (PTTM) resulting from diffuse-type
      adenocarcinoma of the stomach.

PMID- 11827421
TI  - Test and teach. Surgically correctable hypertension. Conn's syndrome and
      spironolactone bodies.

PMID- 11827422
TI  - Increased expression of transforming growth factor-alpha in a patient with
      recurrent hepatocellular carcinoma following partial hepatectomy.
AB  - A 45-year-old woman with chronic hepatitis B underwent partial hepatectomy for
      hepatocellular carcinoma (HCC). However, the HCC recurred 2 months after surgery
      and rapid progression of the disease resulted in her death. Immunohistochemistry
      showed that transforming growth factor-alpha (TGFalpha) was barely expressed in
      the liver specimens obtained at hepatic resection, whereas autopsy specimens were
      strongly stained with anti-TGFalpha antibody in the cytoplasm of both non
      tumourous and tumourous liver cells. A higher level of Ki67 expression, a
      proliferating marker, was observed in the recurrent HCC, similar to that of
      TGFalpha. Thus, we speculate that the partial hepatectomy increased the level of
      TGFalpha leading to recurrence and progression of HCC through an
      autocrine/paracrine mechanism.

PMID- 11827423
TI  - Myxoid invasive papillary urothelial carcinoma of the bladder and urethra.
AB  - An unusual case of myxoid transitional cell (urothelial) carcinoma occurring in a
      75-year-old man is presented. The primary tumour in the bladder, which was
      treated by partial cystectomy, consisted of areas of conventional high grade
      invasive (into the lamina propria) papillary urothelial carcinoma with separate
      myxoid areas. The latter component accounted for 25% of the tumour. Nine months
      later, the patient presented with haematuria once again, and a tumour was
      detected in the urethra. This was excised and histological examination showed
      only myxoid tumour without any overlying dysplasia or obvious epithelial
      differentiation. The myxoid areas were positive for epithelial markers and
      negative for all mesenchymal markers. This case highlights an uncommon variety of
      papillary urothelial carcinoma that invokes a wide differential diagnosis.
      Immunohistochemistry is essential in making the correct diagnosis.

PMID- 11827424
TI  - Synvisc perisynovitis.
AB  - Synvisc (hylan G-F 20) is a high molecular weight hyaluronan which is
      manufactured from chicken combs. It is currently one of the options used in the
      treatment of severe osteoarthritis of the knee joint. Synvisc is directly
      injected into the diseased joint, where it provides elasticity and viscosity.
      Published experience suggests than Synvisc is a safe and well-tolerated material
      with occasional mild local reactions but no long-term adverse sequelae. This
      article describes a case of Synvisc-related granulomatous inflammation in the
      perisynovial adipose tissue. To our knowledge, this is the first histological
      account of tissue reaction to Synvisc.

PMID- 11827425
TI  - Lethal prenatal onset infantile cortical hyperostosis (Caffey disease).
AB  - We describe a sporadic case of lethal prenatal onset infantile cortical
      hyperostosis (Caffey disease), which resulted in early postnatal death at 30
      weeks gestation. The mother presented with antepartum haemorrhage and preterm
      labour. She was found to have polyhydramnios. The infant showed extensive
      symmetrical diaphyseal subperiosteal cortical thickening throughout the skeleton
      with short extremities. Hepatomegaly and lung hypoplasia were present. Currently,
      in the absence of a specific marker, diagnostic ultrasound offers the only
      prospect of prenatal diagnosis. This diagnosis should be considered in infants
      with short angulated long bones, where the diaphyses are irregular and echodense,
      and where there is no sign of fractures.

PMID- 11827426
TI  - Case report: plexiform schwannoma of the vulva.
AB  - We describe a case of plexiform schwannoma, a benign tumour of the peripheral
      nerve sheath, arising in the labia of a 5-year-old girl who presented with a mass
      in the vulva. Light and electron microscopy, special stains and
      immunohistochemistry studies were done on the excised specimen. A Medline search
      revealed a single case of vulvar plexiform schwannoma which was reported in 1983.

PMID- 11827427
TI  - Atypical presentation of herpes simplex (chronic hypertrophic herpes) in a
      patient with HIV infection.
AB  - A 46-year-old man with HIV infection and AIDS presented with a large perianal
      ulcerated vegetative lesion that developed over a 1-year period. He had a past
      history of recurrent genital herpes infection, treated successfully each time
      with acyclovir. The perianal lesion developed while he was taking prophylactic
      acyclovir. Clinically, there were features suspicious of a carcinoma and a biopsy
      was reported as showing dysplasia. Therefore, the lesion was resected in its
      entirety. Histologically, there were prominent pseudo-epitheliomatous hyperplasia
      and chronic ulceration associated with herpesvirus infection. There was no
      evidence of dysplasia or malignancy. It is important to be aware of chronic
      vegetant herpesvirus infection, as clinical appearances are unusual and some
      methods of identification, such as smears or biopsy, may not be sufficient for
      diagnosis. Viral culture or PCR may need to be performed for a definite diagnosis
      to alleviate prolonged discomfort and avoid unnecessary radical surgery.

PMID- 11827428
TI  - Recurrent Methylobacterium mesophilicum sepsis associated with haemodialysis.
AB  - Methylobacterium mesophilicum is an environmental organism that has infrequently
      been implicated as a human pathogen. Most reported cases are in immunocompromised
      hosts. The natural ecology of this organism is related to vegetation or soil. We
      report the case of a 51-year-old man who developed a recurrent bacteraemia with
      this organism while receiving haemodialysis through an indwelling intravascular
      catheter. The literature on the clinical significance of this organism is
      reviewed together with specific microbiological identifying features which could
      be of use in the routine diagnostic laboratory.

PMID- 11827429
TI  - Polyp of the fallopian tube.
AB  - The case of a 34-year-old woman who had a radical hysterectomy for stage 1 b
      squamous cell carcinoma of the cervix and in whom an epithelial polyp was
      identified in the left fallopian tube is presented. The case is unusual in that
      the polyp developed in the absence of any evidence of tubal damage as
      demonstrated by a history of endometriosis or tubal sterilisation.

PMID- 11827431
TI  - Effect of advanced glycation endproducts on the secretion of insulin-like growth
      factor-I and its binding proteins: role in osteoblast development.
AB  - In chronically uncompensated diabetes mellitus, an increase has been observed in
      the content of advanced glycation endproduct (AGE)-modified proteins in various
      tissues, including bone. This increase can lead to a local imbalance in the
      secretion of cytokines and growth factors, and has been implicated in the
      pathophysiology of the longterm complications of diabetes. We have previously
      shown that the proliferation and differentiation of UMR106 rat osteosarcoma and
      MC3T3E1 mouse calvaria-derived cell lines are regulated by AGE-modified proteins,
      possibly through the recognition of these AGEs by specific membrane-associated
      receptors. In the present study, we investigated the effects of AGE-proteins on
      the secretion of insulin-like growth factor-I (IGF-I) and its binding proteins
      (IGFBPs) by both osteoblast-like cell lines. In the case of MC3T3E1 cells, this
      was studied throughout their successive stages of development: proliferation,
      differentiation and mineralisation. For every condition, cells were incubated 24
      hours with increasing concentrations of either bovine serum albumin (BSA) or AGE
      BSA. IGF-I in conditioned media was separated from IGFBPs by acid gel filtration
      centrifugation, and measured by radioimmunoassay. IGFBPs in conditioned media
      were analysed by a semi-quantitative western ligand blot. In UMR106 cells, low
      doses of AGE-BSA significantly decreased the secretion of both IGF-I (56% of
      control) and a 24 kDa IGFBP (80% of control). Results for MC3T3E1 cells, which
      predominantly secrete 29 kDa IGFBPs, were dependent on the stage of development.
      In proliferating preosteoblastic cells, AGE-BSA decreased the secretion of IGF-I
      (34%-37% of control) while increasing the secretion of IGFBP (124%-127% of
      control). On the other hand, secretion of these components of the IGF system by
      mature (differentiated) cells was unaffected by the presence of AGE-BSA. When
      these cells finally attained mineralisation, incubation with AGE-modified BSA
      provoked an increase both in IGFBP (131%-169% of control) and in IGF-I secretion
      (119%-123% of control). The presented evidence suggests that the modulation of
      growth and development by AGE-modified proteins, previously described for both
      cell lines, could be the result of an autocrine-paracrine mechanism involving the
      IGF-IGFBP system.

PMID- 11827432
TI  - Mutation in hepatocyte nuclear factor-1alpha is not a common cause of MODY and
      early-onset type 2 diabetes in Korea.
AB  - Maturity-onset diabetes of the young (MODY)-3 with a mutation in hepatocyte
      nuclear factor (HNF)-1alpha has been identified in most races, but the prevalence
      of Korean MODY and early-onset type 2 diabetes with a mutation in this gene is
      unknown. To determine the prevalence of MODY and early-onset type 2 diabetes with
      the mutation of HNF-1alpha gene in Korea, we analyzed this gene in 69 Korean
      early-onset type 2 diabetics and in 35 healthy persons using the single-strand
      conformation polymorphism (SSCP) technique and direct sequencing. We identified
      one mutation in exon 4 (C900A) in only one of the 69 Korean subjects with early
      onset type 2 diabetes; this mutation was silent and did not change the amino acid
      (Pro300). Additionally, we identified four polymorphisms: S487N, AAC-->AGC,
      intron 2 (nt -23), intron 7: (nt +7) and intron 9 (nt -24). However, there was no
      significant difference in frequencies of the four polymorphisms between the type
      2 diabetes and control groups. Among type 2 diabetics, codon 487 variant showed
      no relationship to age at onset, body mass index, fasting blood glucose, HbA1c,
      lipid profile, basal C-peptide and 2 hour C-peptide. We concluded that this
      genetic mutation in HNF-1alpha gene may not be a common contributor to MODY and
      early-onset type 2 diabetes susceptibility in Korea.

PMID- 11827430
TI  - Lack of gender difference in acetazolamide-induced cerebral vasomotor reactivity
      in patients suffering from type-1 diabetes mellitus.
AB  - The aim of the present work was to investigate the impact of gender on resting
      cerebral blood flow velocity and cerebrovascular reserve capacity among diabetic
      patients. Middle cerebral artery mean blood flow velocity (MCAV) was measured in
      72 patients suffering from type 1 diabetes mellitus at rest and 5, 10, 15 and 20
      min after intravenous administration of 1 g acetazolamide. Cerebrovascular
      reserve was calculated as the maximal percent increase in MCAV after
      acetazolamide. Resting MCAV and cerebrovascular reserve capacity were compared
      between males and females. Resting cerebral blood flow velocity was higher in
      diabetic females than in males (men, 55.0+/-17.0 cm/s; women, 64.4+/-12.6 cm/s,
      p=0.0094). Cerebrovascular reserve capacity was similar in diabetic women and men
      (men, 44.0%+/-18.6%; women, 52.6%+/-32.9%, p=0.17). Comparing MCAV and
      cerebrovascular reserve capacity among the diabetic subgroups with disease
      duration < or = 10 years and >10 years, we did not detect any differences between
      women and men. Duration of diabetes was an important factor in determining
      cerebrovascular reserve capacity in both sexes: long-term diabetic women and men
      showed lower CRC values than diabetics with < or = 10 years disease duration.
      Cerebrovascular reserve capacity is similar in diabetic women and men. Taking
      into consideration that cerebrovascular reserve is normally higher among women,
      our finding indicates a relatively more serious worsening of cerebral
      vasodilatory responses in women suffering from type 1 diabetes.

PMID- 11827433
TI  - Image analysis for the detection of increased erythrocyte, leukocyte and platelet
      adhesiveness/aggregation in the peripheral blood of patients with diabetes
      mellitus.
AB  - Increased erythrocyte, leukocyte, and platelet adhesiveness and aggregation may
      contribute to the development of ischemic vascular conditions in diabetic
      patients. They have been described by using different diagnostic systems and
      following various ex vivo manipulations. We have adopted a simple slide test and
      image analysis to reveal the adhesiveness and aggregation of the three cellular
      elements in a picture that is obtained from one single citrated venous blood
      sample presented on a glass slide. A significant increment in the degree of
      adhesiveness/aggregation of erythrocytes, leukocytes and platelets was noted in
      29 patients with diabetes mellitus as opposed to age- and gender-matched healthy
      controls. It is feasible to look at the increased state of
      adhesiveness/aggregation of erythrocytes, leukocytes and platelets present in
      their native milieu and following minimal manipulation by using an almost real
      time and low cost procedure.

PMID- 11827434
TI  - Benfotiamine is similar to thiamine in correcting endothelial cell defects
      induced by high glucose.
AB  - We investigated the hypothesis that benfotiamine, a lipophilic derivative of
      thiamine, affects replication delay and generation of advanced glycosylation end
      products (AGE) in human umbilical vein endothelial cells cultured in the presence
      of high glucose. Cells were grown in physiological (5.6 mM) and high (28.0 mM)
      concentrations of D-glucose, with and without 150 microM thiamine or
      benfotiamine. Cell proliferation was measured by mitochondrial dehydrogenase
      activity. AGE generation after 20 days was assessed fluorimetrically. Cell
      replication was impaired by high glucose (72.3%+/-5.1% of that in physiological
      glucose, p=0.001). This was corrected by the addition of either thiamine (80.6%+/
      2.4%, p=0.005) or benfotiamine (87.5%+/-8.9%, p=0.006), although it not was
      completely normalized (p=0.001 and p=0.008, respectively) to that in
      physiological glucose. Increased AGE production in high glucose (159.7%+/-38.9%
      of fluorescence in physiological glucose, p=0.003) was reduced by thiamine
      (113.2%+/-16.3%, p=0.008 vs. high glucose alone) or benfotiamine (135.6%+/-49.8%,
      p=0.03 vs. high glucose alone) to levels similar to those observed in
      physiological glucose. Benfotiamine, a derivative of thiamine with better
      bioavailability, corrects defective replication and increased AGE generation in
      endothelial cells cultured in high glucose, to a similar extent as thiamine.
      These effects may result from normalization of accelerated glycolysis and the
      consequent decrease in metabolites that are extremely active in generating
      nonenzymatic protein glycation. The potential role of thiamine administration in
      the prevention or treatment of vascular complications of diabetes deserves
      further investigation.

PMID- 11827435
TI  - Gastric emptying in an animal model of human diabetes type 1: relation to
      endocrine cells.
AB  - Gastric emptying was measured in female non-obese diabetic (NOD) mice with a
      duration of diabetes of 28-35 days. As controls, age- and sex-matched BLAB/cJ
      mice were used. Gastric emptying of diabetic mice was significantly slower than
      that of controls. The faeces weight and water content were significantly higher
      in diabetic mice than controls. The endocrine cells known to correlate with
      gastric emptying, namely secretin, serotonin, peptide YY (PYY) and enteroglucagon
      cells, were identified by immunocytochemistry and quantified by computer image
      analysis. The densities of duodenal secretin, serotonin and colonic PYY cells in
      NOD mice were significantly higher than that of control mice. Changes in these
      three endocrine cell types may play a role in delayed gastric emptying and in the
      manifestation of diarrhoea in this animal model of human diabetes type 1.

PMID- 11827436
TI  - Pancreatic volume in type 1 and type 2 diabetes mellitus.
AB  - We measured pancreatic volume (PV) using helical computed tomography (CT) in 26
      patients with type 1 diabetes mellitus (DM), 29 patients with type 2 DM, and 22
      healthy individuals. We also evaluated the relationship between PV and the body
      surface area (BSA), established the pancreatic volume index (PVI) by dividing PV
      by BSA to correct PV for the body build, and examined its relationships with the
      duration of illness, serum C-peptide immunoreactivity level (CPR), and serum
      immunoreactive trypsin level (IRT). BSA and PV were correlated significantly
      (p<0.0001, r=0.645) in healthy individuals, and they were correlated also in the
      diabetic patients (p=0.0023, r=0.563 in type 1 DM; p=0.0346, r=0.392 in type 2
      DM). PV was significantly smaller in the type 1 DM group than in the healthy
      group and type 2 DM group (p<0.001 for both). PVI was also significantly smaller
      in the type 1 DM group than in the healthy group and type 2 DM group (p<0.001 for
      both). PVI and IRT were significantly correlated in both DM groups (p<0.0001,
      r=0.732 in type 1 DM; p=0.0469, r=0.371 in type 2 DM). PVI was not correlated
      with the duration of illness or CPR. Helical CT was useful for the measurement of
      the pancreatic volume, and the pancreatic volume was reduced particularly in the
      patients with type 1 DM. A strong correlation was observed between PV and
      exocrine pancreatic function in type 1 DM, but the correlation between PV and
      exocrine pancreatic function was weak in type 2 DM.

PMID- 11827437
TI  - EMEA extends indications for metformin. A decision that relies on evidence-based
      medicine.

PMID- 11827438
TI  - Personal names and the human right hemisphere: an illusory link?
AB  - Names are thought to be represented in the brain differently from common nouns.
      Although this idea is supported by both theoretical and empirical arguments, the
      brain areas that are relevant for the recognition of personal names-and in
      particular the extent of right hemisphere involvement-remain controversial. We
      investigated the hypothesis that, unlike common nouns, personal names are
      represented preferentially by the right hemisphere (D. Van Lancker, 1991; D. Van
      Lancker et al., 1991; C. Ohnesorge & D. Van Lancker, 1999). Participants
      performed lexical decisions to common nouns and pseudowords (Experiment 1) or
      familiarity decisions to personal names (Experiment 2), which were presented
      briefly to the left or right visual fields. Asymmetries were small or absent for
      both pseudowords and unfamiliar names. For familiar names, both reaction times
      and error rates revealed strong advantages for the right visual field/left
      hemisphere (RVF/LH), which were comparable to the asymmetries for nouns. Familiar
      personal names may be represented by brain systems that differ from those
      representing common nouns, but current evidence does not suggest a distinct
      contribution of the right hemisphere to these brain systems.

PMID- 11827439
TI  - Personally familiar proper names are relatively successfully processed in the
      human right hemisphere; or, the missing link.
AB  - Responding to our abstract in Brain and Language (Ohnesorge & Van Lancker, 1999),
      which proposed that famous proper nouns are successfully processed in both
      cerebral hemispheres, Schweinberger, Landgrebe, Mohr, and Kaufmann (2001) claimed
      that the "link" between personal names and the right hemisphere is "illusory."
      Ohnesorge and Van Lancker (2001) further described six experimental studies in
      which LVF/RH recognition of famous proper nouns was influenced by task conditions
      and stimulus familiarity. Here presenting two more experiments performed to
      explore the refutation presented by Schweinberger et al., this article confirms
      an ability of the right hemisphere to recognize famous proper nouns and explains
      why appropriate stimulus development and task conditions are essential in
      furthering our understanding of the role of the right hemisphere in processing
      personal relevance.

PMID- 11827440
TI  - Probing hemispheric processes in an on-line reading task.
AB  - Coney (1998) used a priming procedure to obtain evidence that the left and right
      hemispheres contributed equally to lexical processing of concrete nouns in a
      continuous reading task. In that study, however, there was no direct validation
      of the involvement of the right hemisphere in the task, and the possibility of
      left hemisphere processing of left visual field target stimuli could not be ruled
      out. The present study was designed to obtain validating evidence by using
      abstract and concrete noun primes in a similar reading task on the assumption
      that if the right hemisphere was contributing to the task there would be
      demonstrable differences between the visual fields in processing targets primed
      by abstract nouns. The results supported this expectation. While concrete targets
      projected to each visual field were primed by concrete nouns, there was
      significant priming by abstract nouns only in respect of targets presented to the
      right visual field. It is argued that this finding supports the involvement of
      the right hemisphere in continuous reading and further delimits the scope of its
      contribution to this process. Somewhat unexpectedly, the results also revealed
      that absolute response times were faster to left visual field targets when they
      were preceded by abstract nouns, even when there was no semantic relationship
      between the two words. It was suggested that this effect derives from the
      inability of the right hemisphere to process abstract nouns in that the failure
      of abstract nouns to engage lexical processing mechanisms leaves the right
      hemisphere relatively unencumbered when required to process a subsequent target.

PMID- 11827441
TI  - Lexical, morphological, and syntactic aspects of verb production in agrammatic
      aphasics.
AB  - Agrammatic aphasics do not exhibit a normal pattern of verb production; their
      spontaneous speech is said to lack verbs, and the verbs that are produced lack
      inflection. The current article focuses on the lexical, morphological, and
      syntactic aspects of verbs in spontaneous speech of a group of Dutch agrammatic
      speakers. Dutch is a so-called verb-second language in which the finite verb in
      the matrix clause is in the second position and nonfinite verbs are in the final
      position. The analysis shows that agrammatic speakers are sensitive to this
      relation; they virtually never produce finite verbs in the final clause position
      or nonfinite verbs in the second position. Nevertheless, they produce
      significantly fewer finite clauses than do non-brain-damaged speakers. The
      diversity of the lexical verbs in spontaneous speech is also lower than in non
      brain-damaged speakers, but this is due to less variation in the finite lexical
      verbs. Hence, it is suggested that the problems with verbs in Dutch agrammatic
      spontaneous speech are restricted to finite lexical verbs. In an experiment, it
      was evaluated whether these problems with finite lexical verbs are caused by a
      morphological deficit or a syntactic deficit. The data show that a syntactic
      deficit is more likely; Dutch agrammatic speakers produce finite verbs in the
      base-generated position (i.e., in the embedded clause) significantly better than
      finite verbs that have been moved to the second position (i.e., in the matrix
      clause). From these data, the authors conclude that in Dutch, a verb-second
      language, agrammatic aphasics demonstrate specific problems with moved finite
      verbs, although they are perfectly aware of the relation between verb position
      and verb finiteness. This syntactic problem affects not only the proportion of
      finite verbs but also the diversity of the verbs and, hence, communicative
      contents.

PMID- 11827442
TI  - Question production in agrammatism: the tree pruning hypothesis.
AB  - This study investigated question production in agrammatic aphasia, focusing on
      the comparison between Wh questions and yes/no questions and on the interaction
      between the question production deficit and language-specific properties. A total
      of 16 agrammatic aphasics (13 Hebrew speakers, 2 Palestinian Arabic speakers, and
      1 English speaker) participated in the study, which included sentence elicitation
      and repetition tasks. In addition, the patients' spontaneous speech, containing
      2272 utterances, was analyzed. The main findings were that Hebrew- and Arabic
      speaking agrammatics encounter severe difficulties in Wh question production but
      retain the ability to produce yes/no questions. English-speaking agrammatics do
      not show this dissociation and can form neither Wh nor yes/no questions. These
      dissociations as well as the error pattern, are explained by reference to the
      Tree Pruning Hypothesis, according to which the highest nodes of the syntactic
      tree, which are required for Wh questions in Hebrew, Arabic, and English and for
      yes/no questions in English, are impaired or inaccessible in agrammatism.

PMID- 11827443
TI  - Switching languages, switching palabras (words): an electrophysiological study of
      code switching.
AB  - Switching languages has often been associated with a processing cost. In this
      study, the authors used event-related potentials to compare switches between two
      languages with within-language lexical switches as bilinguals read for
      comprehension. Stimuli included English sentences and idioms ending either with
      the expected English words, their Spanish translations (code switches), or
      English synonyms (lexical switches). As expected, lexical switches specifically
      enhanced the N400 response in both context types. Code switches, by contrast,
      elicited an increased negativity over left fronto-central sites in the regular
      nonidiomatic sentences (250-450 ms) and a large posterior positivity (450-850 ms)
      in both context types. In addition, both lexical and code switches elicited a
      late frontal positivity (650-850 ms) relative to expected completions, especially
      in idioms. Analysis of the individual response patterns showed correlations with
      vocabulary skills in English and in Spanish. Overall, the electrophysiological
      data suggest that for some speakers in some contexts, the processing of a code
      switch may actually be less costly than the processing of an unexpected within
      language item.

PMID- 11827444
TI  - Auditory temporal processing deficits in children with periventricular brain
      injury.
AB  - The present study investigated whether auditory temporal processing deficits are
      related to the presence and/or the severity of periventricular brain injury and
      the reading difficulties experienced by extremely low birthweight (ELBW:
      birthweight <1000 g) children. Results indicate that ELBW children with mild or
      severe brain lesions obtained significantly lower scores on a test requiring
      auditory temporal order judgments than ELBW children without periventricular
      brain injury or children who were full-term. Structural equation modeling
      indicated that a model in which auditory temporal processing deficits predicted
      speech sound discrimination and phonological processing ability provided a better
      fit for the data than did a second model, which hypothesized that auditory
      temporal processing deficits are associated with poor reading abilities through a
      working memory deficit. These findings suggest that an impairment in auditory
      temporal processing may contribute to the reading difficulties experienced by
      ELBW children.

PMID- 11827445
TI  - Age-related differences in inference revision processing.
AB  - In comparison to younger adults, older adults demonstrate deficiencies in
      cognitive and linguistic abilities. Such cognitive factors that decline with age
      include working memory capacity and inhibitory abilities. The purpose of the
      present investigation was to measure differences in time course processing of
      inference revision abilities, as well as working memory, as they exist relative
      to adult age differences. Fifteen neurologically intact older adults and 15
      younger adults participated in this study. A cross-modal lexical priming paradigm
      was chosen as the measure of the inference revision task; the listening span task
      of Tompkins, Bloise, Timko, and Baumgaertner (1994) was selected as the measure
      of working memory. Both groups demonstrated normal priming effects. No age
      related differences were found on the working memory measure. Age-related
      differences did emerge on inferencing abilities. A significant correlation
      emerged between the older group's performance on comprehending inference
      revisions and their working memory capacity. Generally, inhibitory abilities and
      working memory capacity appeared to adversely affect older participant's
      performance.

PMID- 11827446
TI  - Electrophysiological evidence for priming in response to words and pseudowords in
      first and second language.
AB  - The study purpose was to indicate when language-specific processing first occurs
      and how first and second language priming processes interact. Event-related
      potentials were recorded from 14 normal native Hebrew speakers, in a variation of
      lexical decision task, to pairs of stimuli (S1, S2) in Hebrew, English, Hebrew
      pseudowords, and English pseudowords. Although no behavioral priming was
      observed, priming by pseudowords in either language affected both N400 and the
      late positive component of event related potential. N1 and P2 latencies were
      longer to S2 in semantically related pairs, indicating that language-specific
      processing may take place as early as auditory cortex. Different processing of
      first and second language was evident only in response to pseudowords.

PMID- 11827447
TI  - Neurological origins of poor reading comprehension despite fast word decoding?
AB  - Barnes, Faulkner, and Dennis (2001) found that hydrocephalic children (mean age =
      11.5 years) of average or above-average verbal intelligence exhibit poor reading
      comprehension despite their fast and accurate decoding skills on individual
      words. This finding attracts the attention of reading researchers because it
      appears to be against the following standard principle of reading comprehension
      failure (Gough & Hillinger, 1980), thereby provoking basic issues centering
      around it (e.g., Stanovich, 1991): Reading Comprehension = Word Decoding x
      Listening Comprehension. This formula indicates that when listening comprehension
      is kept well within the normal range, reading comprehension is highly correlated
      with word decoding (e.g., Perfetti, 1985). In contrast, with poor listening
      comprehension children would be poor readers however good they may be at reading
      words (e.g., Cain, Oakhill, & Bryant, 2000). Although Barnes et al. clearly
      demonstrated that children with hydrocephalus decoded individual words better
      than they comprehended text, it is not readily apparent whether their findings
      are inconsistent with the standard principle. The purpose of the present article
      is twofold. The first is to examine whether Barnes et al.'s findings constitute a
      counterexample of the above principle. (Note that Barnes et al. did not address
      this question.) The second and more important purpose is to discuss the possible
      origins of the decoding-better-than-sentence/text-comprehension pattern. We also
      present some pedagogical implications for poor readers such as hydrocephalic
      children.

PMID- 11827450
TI  - Bringing in the clones.

PMID- 11827451
TI  - Identification and characterization of FTSJ2, a novel human nucleolar protein
      homologous to bacterial ribosomal RNA methyltransferase.
AB  - Cellular RNAs in eukaryotes undergo extensive posttranscriptional modifications,
      but as yet only a few RNA-modifying enzymes have been identified and
      characterized. Here we report on the cloning of FTSJ2, a novel human gene
      encoding a putative RNA methyltransferase. FTSJ2 shares significant sequence
      homology with FtsJ/RrmJ, a recently identified Escherichia coli 23S rRNA uridine
      2'-O-methyltransferase. FTSJ2 belongs to a new family of evolutionarily conserved
      S-adenosylmethionine-binding proteins. The gene FTSJ2 is located on chromosome
      7p22 between MAD1L1 and NUDT1. It is 8 kb in length, spanning three exons.
      Northern blot analysis revealed that the FTSJ2 transcripts are abundant in
      skeletal muscle, placenta, and heart, as well as in cancer cells.
      Immunofluorescence staining demonstrated that FTSJ2 protein localizes to the
      nucleolus. Our results suggest that FTSJ2 is likely a nucleolar RNA
      methyltransferase involved in eukaryotic RNA processing and modification.

PMID- 11827452
TI  - Gene expression profile of human bone marrow stromal cells: high-throughput
      expressed sequence tag sequencing analysis.
AB  - Human bone marrow stromal cells (HBMSC) are pluripotent cells with the potential
      to differentiate into osteoblasts, chondrocytes, myelosupportive stroma, and
      marrow adipocytes. We used high-throughput DNA sequencing analysis to generate
      4258 single-pass sequencing reactions (known as expressed sequence tags, or ESTs)
      obtained from the 5' (97) and 3' (4161) ends of human cDNA clones from a HBMSC
      cDNA library. Our goal was to obtain tag sequences from the maximum number of
      possible genes and to deposit them in the publicly accessible database for ESTs
      (dbEST of the National Center for Biotechnology Information). Comparisons of our
      EST sequencing data with nonredundant human mRNA and protein databases showed
      that the ESTs represent 1860 gene clusters. The EST sequencing data analysis
      showed 60 novel genes found only in this cDNA library after BLAST analysis
      against 3.0 million ESTs in NCBI's dbEST database. The BLAST search also showed
      the identified ESTs that have close homology to known genes, which suggests that
      these may be newly recognized members of known gene families. The gene expression
      profile of this cell type is revealed by analyzing both the frequency with which
      a message is encountered and the functional categorization of expressed
      sequences. Comparing an EST sequence with the human genomic sequence database
      enables assignment of an EST to a specific chromosomal region (a process called
      digital gene localization) and often enables immediate partial determination of
      intron/exon boundaries within the genomic structure. It is expected that high
      throughput EST sequencing and data mining analysis will greatly promote our
      understanding of gene expression in these cells and of growth and development of
      the skeleton.

PMID- 11827453
TI  - Generation of two homologous and intronless zinc-finger protein genes, zfp352 and
      zfp353, with different expression patterns by retrotransposition.
AB  - We have previously reported a mouse zinc-finger protein gene, Zfp352 (formerly
      2czf48), that is expressed in early mouse embryos. Here, we report the genomic
      structure of Zfp352 and its lung-specific homolog, Zfp353. The two genes map on
      different chromosomes at 4C6 and 8B3.1. Both genes are intronless, except for the
      presence of a single 4.6-kb intron in the 5' untranslated region of Zfp352. The
      genes use different RNA start sites located 1.2 kb apart within the 5' homologous
      region. LINE1 sequences are structurally associated with the genes and form an
      integral part of Zfp353 transcripts, suggesting previous retrotransposition
      events. We propose a model of evolution of the genes. The main feature of the
      model is the presence of a fortuitous upstream promoter and an intron in the
      first retrotransposition site, creating a pre-Zfp352 gene with a 5' untranslated
      region intron. A second retrotransposition event copying from the pre-Zfp352
      retroposon and removing the fortuitous intron resulted in the intronless Zfp353
      at a different chromosomal location and with a different mode of expression. The
      model may be applicable to other genes with a similar structure with a single
      intron in the 5' untranslated region. The exact role of LINE1 in the
      retrotransposition events remains to be elucidated.

PMID- 11827454
TI  - Expression of the mouse gap junction gene Gjb3 is regulated by distinct
      mechanisms in embryonic stem cells and keratinocytes.
AB  - Connexins are the protein subunits of gap junction channels and are expressed in
      a highly regulated temporal and spatial pattern in embryonic development and
      adult life, with most cell types expressing more than one isoform. Connexin31
      (Cx31) is encoded by the gene Gjb3 and expressed throughout mouse development n a
      complex pattern; in adult mice it becomes restricted to the granular layer of
      epidermis, testis, and placenta. In placenta, lack of Cx31 leads to transient
      dysmorphogenesis affecting embryonic survival. Here we have analyzed the
      structure of mouse Gjb3 as well as its transcriptional regulation by transient
      transfection of reporter gene constructs in HM1 mouse embryonic stem cells and a
      mouse keratinocytederived cell line, Hel37, as model systems for early
      development and skin, respectively. Like most connexin genes, Gjb3 is composed of
      two exons, the second of which contains the whole coding region and is separated
      from the first exon by an intron of 2.3 kb. Expression in keratinocytes is
      regulated by a basal promoter extending to 561 bp upstream of exon 1 in
      conjunction with a regulatory region between upstream positions 561 and 841. In
      contrast, expression of Gjb3 in embryonic stem cells depended on the basal
      promoter together with the intron. The enhancing effect of the intron was found
      only in embryonic stem cells and depended on its native position and the
      integrity of the splice sites. Thus, expression of Gjb3 in keratinocytes and
      embryonic stem cells is regulated by different cis-regulatory elements and
      differs in its requirements for the intron in situ.

PMID- 11827455
TI  - Physical and genetic characterization reveals a pseudogene, an evolutionary
      junction, and unstable loci in distal Xq28.
AB  - A large portion of human Xq28 has been completely characterized but the interval
      between G6PD and Xqter has remained poorly understood. Because of a lack of
      stable, high-density clone coverage in this region, we constructed a 1.6-Mb
      bacterial and P1 artificial chromosome (BAC and PAC, respectively) contig to
      expedite mapping, structural and evolutionary analysis, and sequencing. The
      contig helped to reposition previously mismapped genes and to characterize the
      XAP135 pseudogene near the int22h-2 repeat. BAC clones containing the distal
      int22h repeats also demonstrated spontaneous rearrangements and sparse coverage,
      which suggested that they were unstable. Because the int22h repeats are involved
      in genetic diseases, we examined them in great apes to see if they have always
      been unstable. Differences in copy number among the apes, due to duplications and
      deletions, indicated that they have been unstable throughout their evolution.
      Taking another approach toward understanding the genomic nature of distal Xq28,
      we examined the homologous mouse region and found an evolutionary junction near
      the distal int22h loci that separated the human distal Xq28 region into two
      segments on the mouse X chromosome. Finally, haplotype analysis showed that a
      segment within Xq28 has resisted excessive interchromosomal exchange through
      great ape evolution, potentially accounting for the linkage disequilibrium
      recently reported in this region. Collectively, these data highlight some
      interesting features of the genomic sequence in Xq28 and will be useful for
      positional cloning efforts, mouse mutagenesis studies, and further evolutionary
      analyses.

PMID- 11827457
TI  - Complementation of a yeast CYC3 deficiency identifies an X-linked mammalian
      activator of apocytochrome c.
AB  - We have shown by indirect immunofluorescence and enhanced green fluorescent
      protein fusions that a mammalian sequence exhibiting similar levels of homology
      to the two yeast heme lyases Cyc3p (holocytochrome c synthase; HCCS) and Cyt2p
      (holocytochrome c1 synthase; HCC1S) is also targeted to mitochondria. The human
      protein was able to complement the yeast Cyc3p (but not Cyt2p) deficiency, which
      indicates that it specifically activates apocytochrome c. Consistent with a
      respiratory role, expression of the mammalian gene was detected in all tissues,
      with the highest levels found in heart. Notably, the human gene HCCS is the only
      known gene located within the critical region for the deletion-defined disorder
      microphthalmia with linear skin defects (MLS). We believe the spectrum of
      clinical features seen in females with MLS and the paucity of male patients are
      consistent with significant involvement of HCCS. Toward clarification of a role
      for HCCS in disease, we have extensively characterized the X-linked mouse Hccs
      genomic locus, showing conservation in gene size and arrangement despite its
      location in a region that has undergone significant evolutionary rearrangement.

PMID- 11827456
TI  - Physical and transcript map of the hereditary prostate cancer region at xq27.
AB  - We have recently mapped a locus for hereditary prostate cancer (termed HPCX) to
      the long arm of the X chromosome (Xq25-q27) through a genome-wide linkage study.
      Here we report the construction of an approximately 9-Mb sequence-ready bacterial
      clone contig map of Xq26.3-q27.3. The contig was constructed by screening BAC/PAC
      libraries with markers spaced at approximately 85-kb intervals. We identified
      overlapping clones by end-sequencing framework clones to generate 407 new
      sequence-tagged sites, followed by PCR verification of overlaps. Contig assembly
      was based on clone restriction fingerprinting and the landmark information. We
      identified a minimal overlap contig for genomic sequencing, which has yielded 7.7
      Mb of finished sequence and 1.5 Mb of draft sequence. The transcriptional mapping
      effort localized 57 known and predicted genes by database searching, STS content
      mapping, and sequencing, followed by sequence annotation. These transcriptional
      units represent candidate genes for HPCX and multiple other hereditary diseases
      at Xq26.3-q27.3.

PMID- 11827458
TI  - Paternal origins of complete hydatidiform moles proven by whole genome single
      nucleotide polymorphism haplotyping.
AB  - Complete hydatidiform moles (CHMs) are diploid tumors that result from
      fertilization of an empty ovum by a haploid 23,X sperm. In most cases, the
      resulting duplication of the genome gives rise to a 46,XX genotype and is thought
      to be androgenetic in origin. If this hypothesis is correct, then the genotypes
      of all polymorphic markers in CHMs should be homozygous. We used a dense set of
      single-nucleotide polymorphism (SNP) markers, evenly spaced throughout the
      genome, to definitively test this hypothesis. We genotyped genomic DNA samples
      from five CHMs and their corresponding maternal samples with 1494 SNP markers
      using high-density microarrays (HuSNP). As predicted, the maternal samples were
      heterozygous at >25% of the markers, which is consistent with the expected
      average heterozygosity of this panel of SNPs. In contrast, the five CHM samples
      were heterozygous at <0.75% of the SNP markers, which shows that these diploid
      tumors consist of a duplicated set of chromosomes. Because the CHM genotypes
      represent the haplotypes of their genomes, our results show that long-range
      haplotypes can be obtained easily with this resource and that a collection of
      such samples is a simple way to obtain reference haplotypes for association
      studies in various populations.

PMID- 11827459
TI  - Multiple transcription initiation sites, alternative splicing, and differential
      polyadenylation contribute to the complexity of human neurofibromatosis 2
      transcripts.
AB  - Northern blot analysis has shown that the human neurofibromatosis type 2 (NF2)
      cDNA hybridizes to multiple RNA species. To examine whether these hybridizing RNA
      species represent NF2 transcripts, we cloned the complete NF2 cDNA by a
      combination of techniques: 5' and 3' rapid amplification of cDNA ends, RT-PCR,
      and searching and sequencing the NF2-related cDNA clones from the IMAGE
      consortium. We showed that human NF2 transcripts initiate at multiple positions.
      Analogous to those reported previously, NF2 transcripts undergo alternative
      splicing in the coding exons. We isolated eight alternatively spliced NF2 cDNA
      isoforms, including one that contains a new exon termed exon 2', which
      potentially could encode proteins of different sizes. We assembled the
      overlapping cDNA fragments, and the longest NF2 cDNA, containing all 17 exons,
      consists of 6067 nucleotides, which is consistent with the size of the major RNA
      species hybridized to the NF2 probe. The cDNA has a 425-nucleotide 5'
      untranslated region upstream from the ATG start codon, and a long 3' untranslated
      region of 3869 nucleotides. We also isolated two shorter NF2 cDNAs that were
      terminated by different polyadenylation signal sequences, which indicates that
      differential usage of multiple polyadenylation sites also contributes to the
      complexity of human NF2 transcripts. By reference to the transcription initiation
      site mapped, we analyzed the 5' flanking sequence of the human NF2 gene.
      Transient transfection analysis in human 293 kidney, SK-N-AS neuroblastoma, and
      NT2/D1 teratocarcinoma cells with NF2 promoter-luciferase chimeric constructs
      revealed a core promoter region extending 400 base pairs from the major
      transcription initiation site. Although multiple regions are required for full
      promoter activity, a site-directed mutagenesis experiment identified a GC-rich
      sequence (position -58 to -46), which could be bound by transcription factor Sp1,
      as a positive cis-acting regulatory element. Cotransfection studies in Drosophila
      melanogaster SL2 cells showed that Sp1 could activate the NF2 promoter through
      the GC-rich sequence.

PMID- 11827460
TI  - Wdr12, a mouse gene encoding a novel WD-Repeat Protein with a notchless-like
      amino-terminal domain.
AB  - The WD-repeat protein family consists of a large group of structurally related
      yet functionally diverse proteins found predominantly in eukaryotic cells. These
      factors contain several (4-16) copies of a recognizable amino-acid sequence motif
      (the WD unit) thought to be organized into a "propeller-like" structure involved
      in protein-protein regulatory interactions. Here, we report the cloning of a
      mouse cDNA, referred to as Wdr12, which encodes a novel WD-repeat protein of 423
      amino acids. The WDR12 protein was predicted to contain seven WD units and a
      nuclear localization signal located within a protruding peptide between the third
      and fourth WD domains. The amino-terminal region shows similarity to that of the
      Notchless WD repeat protein. Sequence comparisons revealed WDR12 orthologs in
      various eukaryotic species. Wdr12 seems to correspond to a single-copy gene in
      the mouse genome, located within the C1-C2 bands of chromosome 1. These data,
      together with the results of Wdr12 gene expression studies and evidence of in
      vitro binding of WDR12 to the cytoplasmic domain of Notch1, led us to postulate a
      function for the WDR12 protein in the modulation of Notch signaling activity.

PMID- 11827461
TI  - WAC, a novel WW domain-containing adapter with a coiled-coil region, is
      colocalized with splicing factor SC35.
AB  - WW domains mediate protein-protein interactions in many intracellular processes.
      In pre-mRNA splicing, WW domains participate in cross-intron bridging. These WW
      domains are characterized by a central aromatic block of three tyrosine residues.
      We identified a novel protein containing the same type of WW domain. The gene
      encoding the protein, named WAC, is located in human chromosome 10p11.2-10p12.1.
      A Drosophila melanogaster WAC homolog (CG8949) was identified as a Rosetta stone
      protein. Domain fusion analysis of the Rosetta stone protein linked WAC to
      splicing factor SNRP70. WAC existed mainly in a tyrosine-phosphorylated form.
      Immunofluorescence analysis colocalized WAC with SC35, the marker for pre-mRNA
      splicing machinery. Our analysis suggests that WAC represents a novel member of
      WW-domain-containing proteins for RNA processing.

PMID- 11827462
TI  - The human T-type amino acid transporter-1: characterization, gene organization,
      and chromosomal location.
AB  - System T is a Na+-independent transport system that selectively transports
      aromatic amino acids. Here, we determined the structure of the human T-type amino
      acid transporter-1 (TAT1) cDNA and gene (SLC16A10). The human TAT1 cDNA encoded a
      515-amino-acid protein with 12 putative membrane-spanning domains. Human SLC16A10
      was localized on human chromosome 6, mapped to 6q21-q22. SLC16A10 contains six
      exons spanning 136 kb. In contrast to rat TAT1, which is mainly present in the
      intestine, human TAT1 was strongly expressed in human kidney as well as in human
      intestine. Expression of human TAT1 in Xenopus laevis oocytes demonstrated the
      Na+-independent transport of tryptophan, tyrosine, phenylalanine, and L-dopa,
      indicating that human TAT1 is a transporter subserving system T. Because human
      TAT1 is proposed to be crucial to the efficient absorption of aromatic amino
      acids from intestine and kidney, its defect could be involved in the disruption
      of aromatic amino-acid transport, such as in blue diaper syndrome.

PMID- 11827463
TI  - Characterization of variability in large-scale gene expression data: implications
      for study design.
AB  - Large-scale gene expression measurement techniques provide a unique opportunity
      to gain insight into biological processes under normal and pathological
      conditions. To interpret the changes in expression profiles for thousands of
      genes, we face the nontrivial problem of understanding the significance of these
      changes. In practice, the sources of background variability in expression data
      can be divided into three categories: technical, physiological, and sampling. To
      assess the relative importance of these sources of background variation, we
      generated replicate gene expression profiles on high-density Affymetrix GeneChip
      oligonucleotide arrays, using either identical RNA samples or RNA samples
      obtained under similar biological states. We derived a novel measure of
      dispersion in two-way comparisons, using a linear characteristic function. When
      comparing expression profiles from replicate tests using the same RNA sample (a
      test for technical variability), we observed a level of dispersion similar to the
      pattern obtained with RNA samples from replicate cultures of the same cell line
      (a test for physiological variability). On the other hand, a higher level of
      dispersion was observed when tissue samples of different animals were compared
      (an example of sampling variability). This implies that, in experiments in which
      samples from different subjects are used, the variation induced by the stimulus
      may be masked by non-stimuli-related differences in the subjects' biological
      state. These analyses underscore the need for replica experiments to reliably
      interpret large-scale expression data sets, even with simple microarray
      experiments.

PMID- 11827464
TI  - A cluster of ten novel MHC class I related genes on human chromosome 6q24.2
      q25.3.
AB  - We have identified a novel family of human major histocompatibility complex (MHC)
      class I genes. This MHC class I related gene family is defined by 10 members,
      among which 6 encode potentially functional glycoproteins. The 180-kb cluster
      containing them has been generated by serial duplication and minimal
      diversification of an ancestral prototype. They are not located within the MHC on
      6p21.3, but near the tip of its long arm at q24.2-q25.3, close to the human
      equivalent of the mouse H2-linked t-complex, a subchromosomal region syntenic to
      a segment of mouse chromosome 10 harboring the orthologous MHC class I related
      retinoic acid early transcript loci, Raet1a-d. Hence we have named the identified
      loci RAET1E-N. Human RAET1 products are all devoid of the membrane-proximal
      immunoglobulin-like alpha3 domain and most, but not all, are predicted to remain
      membrane-anchored via glycosylphosphatidylinositol linkage and are shown to
      display an atypical pattern of polymorphism. RAET1 transcripts are absent from
      hematopoietic tissues, but largely expressed in tumors. The involvement of
      orthologous mouse RAET1A-D/H60 in natural killer and T-cell activation through
      NKG2D engagement augurs a similar function for the human RAET1 proteins.

PMID- 11827465
TI  - Sequence analysis of LRPPRC and its SEC1 domain interaction partners suggests
      roles in cytoskeletal organization, vesicular trafficking, nucleocytosolic
      shuttling, and chromosome activity.
AB  - LRPPRC (originally called LRP130) is an intracellular, 130-kD, leucine-rich
      protein that copurifies with the fibroblast growth factor receptor from liver
      cell extracts and has been detected in diverse multiprotein complexes from the
      cell membrane, cytoskeleton, and nucleus. Here we report results of a sequence
      homology analysis of LRPPRC and its SEC1 domain interactive partners. We found
      that 23 copies of tandem repeats that are similar to pentatricopeptide,
      tetratricopeptide, and huntingtin-elongation A subunit-TOR repeats characterize
      the LRPPRC sequence. The amino terminus exhibits multiple copies of leucine-rich
      nuclear transport signals followed by ENTH, DUF28, and SEC1 homology domains. We
      used the SEC1 domain to trap interactive partners expressed from a human liver
      cDNA library. Interactive C19ORF5 (XP_038600) exhibited a strong homology to
      microtubule-associated proteins and a potential arginine-rich mRNA binding motif.
      UXT (XP_033860) exhibited alpha-helical properties homologous to the actin
      associated spectrin repeat and L/I heptad repeats in mobile transcription
      factors. C6ORF34 (XP_004305) was homologous to the non-DNA-binding carboxy
      terminus of the Escherichia coli Rob transcription factor. CECR2 (AAK15343)
      exhibited a transcription factor AT-hook motif next to two bromodomains and a
      homology to guanylatebinding protein-1. Together these features suggest a
      regulatory role of LRPPRC and its SEC1 domain-interactive partners in integration
      of cytoskeletal networks with vesicular trafficking, nucleocytosolic shuttling,
      transcription, chromosome remodeling, and cytokinesis.

PMID- 11827466
TI  - Genomic organization of the genes Gtf2ird1, Gtf2i, and Ncf1 at the mouse
      chromosome 5 region syntenic to the human chromosome 7q11.23 Williams syndrome
      critical region.
AB  - We have recently isolated a mouse ortholog of human GTF2IRD1 that is related to
      GTF2I. GTF2IRD1 and GTF2I proteins are characterized by the presence of multiple
      helix-loop-helix domains and a leucine zipper motif. Both paralogs are closely
      linked and deleted hemizygously in individuals with Williams syndrome, a dominant
      genetic condition characterized by unique neurocognitive and behavioral features.
      We have isolated and analyzed the sequence of bacterial artificial chromosome
      clones from the syntenic mouse chromosome 5 region that contains Gtf2ird1 and
      Gtf2i as well as a neighboring gene, Ncf1. Gtf2ird1 is composed of 31 exons
      spanning >100 kb on mouse chromosome 5 and is located between Cyln2 and Gtf2i.
      Gtf2i is composed of 34 exons spanning about 77 kb. Ncf1, located downstream of
      Gtf2i, consists of 11 exons that extend over 8 kb. The gene organization of
      Gtf2ird1, Gtf2i, and Ncf1 is conserved in mice and humans, although the intronic
      regions are more compact in the mouse genome. The helix-loop-helix repeats of
      Gtf2ird1 and Gtf2i are encoded separately on adjacent exons and were generated by
      independent genomic rearrangements. These studies contribute to our knowledge of
      transcription factor defects and their pathogenesis in haploinsufficiency
      conditions.

PMID- 11827467
TI  - Prevention of mis-aminoacylation of a dual-specificity aminoacyl-tRNA synthetase.
AB  - Accurate aminoacylation of tRNAs by aminoacyl-tRNA synthetase is essential for
      the fidelity of protein synthesis. For Methanococcus jannaschii tRNA(Pro),
      accuracy is difficult because the cognate prolyl-tRNA synthetase also recognizes
      and aminoacylates tRNA(Cys) with cysteine. We show here that the unmodified
      transcript of M. jannaschii tRNA(Pro) is indeed mis-acylated with cysteine.
      However, the origin of mis-charging is not at the anticodon or acceptor stem, the
      two hotspots for tRNA(Pro) and tRNA(Cys) identity determinants. Instead,
      replacement of the D loop in the tRNA core with that of tRNA(Cys) suppresses mis
      charging with cysteine without compromising the activity of aminoacylation with
      proline. The reduced level of cysteine activity of the chimera is not due an
      editing response of the synthetase and is consistent with a relaxed sensitivity
      of the tRNA to the analog thiaproline in aminoacylation with cysteine. We suggest
      that mis-acylation is not due to the presence of cysteine determinants, but to a
      mis-placed 3' end into the cysteine catalytic site that activates and transfers
      cysteine to the tRNA. Prevention of mis-placement by alteration of the core
      structure or by nucleotide modifications in the tRNA illustrates a novel strategy
      of the dual-specificity synthetase.

PMID- 11827468
TI  - Non-cognate template usage and alternative priming by a group II intron-encoded
      reverse transcriptase.
AB  - Group II introns are retroelements that site-specifically insert into DNA through
      homing. They are also implicated in related phenomena such as ectopic site
      insertions and precise intron deletions, but little is known about how group II
      intron reverse transcriptases (RTs) interact with non-cognate substrates. Here we
      show that wild-type aI2 RT readily reverse transcribes non-cognate RNAs in
      mitochondrial RNP particles when the aI2 intron structure is misfolded. In two
      closely related priming mutants, 1degree2(DeltaD5) and 1(+)2(DeltaD5), which
      contain wild-type RT but a disrupted intron structure, the RT has substantially
      lost specificity for aI2 RNA and copies multiple RNAs present in the RNP
      particles, using an alternative priming mechanism. The RT in 1degree2(DeltaD5)
      RNP particles can also copy exogenous RNAs but unlike the endogenous templates, a
      complementary primer is required, suggesting that the alternative priming event
      is specific to RT-RNA interactions formed in vivo. Alternatively primed cDNAs
      from strains 1degree2(DeltaD5), 1(+)2(DeltaD5) and 1degree2(P714T) (containing
      the mutation P714T in the RT) do not use homing site DNA as a primer, but appear
      to utilize a non-complementary DNA primer of approximately ten nucleotides. The
      alternative priming mechanism and reverse transcription of non-cognate templates
      has implications for in vivo reverse transcription of non-intronic RNAs, which is
      expected to occur during intron deletions and other retroprocessing events.

PMID- 11827469
TI  - Suppression of 15-lipoxygenase synthesis by hnRNP E1 is dependent on repetitive
      nature of LOX mRNA 3'-UTR control element DICE.
AB  - Cytidine-rich 15-lipoxygenase differentiation control element (15-LOX DICE) is a
      multifunctional cis-element found in the 3'-UTR of numerous eukaryotic mRNAs. It
      binds KH domain proteins of the type hnRNP E and K, thus mediating mRNA
      stabilization and translational control. Translational silencing is caused by
      formation of a simple binary complex between DICE and recombinant hnRNP E1 (E1).
      Electromobility shift assays and sucrose gradient centrifugation demonstrate that
      rabbit 15-LOX DICE, which is composed of ten subunits of the sequence
      (CCCCPuCCCUCUUCCCCAAG)10=10R, is able to bind up to ten molecules of E1.
      Protein/RNA interaction was studied with different subunits and submotifs of the
      10R structure. Binding appears to be dependent on the degree of polymerization of
      the C-clusters (1R<2R<4R<10R), but not on their order. The minimal motif, which
      still functioned in E1 binding, contained two C-clusters (CCCCPuCCCUCUU). For
      efficient translational control, E1 binding is a necessary, but not sufficient,
      condition. Translational inhibition by E1 is only observed when at least a
      dimeric 2R configuration of the DICE is present in the 3'-UTR of a reporter mRNA.
      We conclude that binding of at least two E1 molecules activate or expose a
      binding site to enable the complex to interact with the 5'-end of the mRNA and
      the translational machinery. DICE-motifs are widely distributed in nature. The
      UTR database UTRnr contains 78 entries of mRNAs with 15-LOX DICEs. Most DICEs
      were two- to fourfold repetitive, but also highly repetitive structures were
      found, as in quail myelin protein mRNA (31 repeats) and hyperglycemic hormone
      mRNA of two crayfish species (nine and 11 repeats).

PMID- 11827470
TI  - Bacteriophage p22 portal vertex formation in vivo.
AB  - Bacteriophage with double-stranded, linear DNA genomes package DNA into pre
      assembled icosahedral procapsids through a unique vertex. The packaging vertex
      contains an oligomeric ring of a portal protein that serves as a recognition site
      for the packaging enzymes, a conduit for DNA translocation, and the site of tail
      attachment. Previous studies have suggested that the portal protein of
      bacteriophage P22 is not essential for shell assembly; however, when assembled in
      the absence of functional portal protein, the assembled heads are not active in
      vitro packaging assays. In terms of head assembly, this raises an interesting
      question: how are portal vertices defined during morphogenesis if their
      incorporation is not a requirement for head assembly? To address this, the P22
      portal gene was cloned into an inducible expression vector and transformed into
      the P22 host Salmonella typhimurium to allow control of the dosage of portal
      protein during infections. Using pulse-chase radiolabeling, it was determined
      that the portal protein is recruited into virion during head assembly.
      Surprisingly, over-expression of the portal protein during wild-type P22
      infection caused a dramatic reduction in the yield of infectious virus. The cause
      of this reduction was traced to two potentially related phenomena. First, excess
      portal protein caused aberrant head assembly resulting in the formation of T=7
      procapsid-like particles (PLPs) with twice the normal amount of portal protein.
      Second, maturation of the PLPs was blocked during DNA packaging resulting in the
      accumulation of empty PLPs within the host. In addition to PLPs with normal
      morphology, smaller heads (apparently T=4) and aberrant spirals were also
      produced. Interestingly, maturation of the small heads was relatively efficient
      resulting in the formation of small mature particles that were tailed and
      contained a head full of DNA. These data suggest that incorporation of portal
      vertices into heads occurs during growth of the coat lattice at decision points
      that dictate head assembly fidelity.

PMID- 11827471
TI  - Two targets in pCF10 DNA for PrgX binding: their role in production of Qa and
      prgX mRNA and in regulation of pheromone-inducible conjugation.
AB  - PrgX is the primary cytoplasmic protein involved in negative control of pheromone
      inducible conjugation functions of the Enterococcus faecalis plasmid pCF10. PrgX
      is believed to act in concert with an antisense RNA called Qa to inhibit
      readthrough of transcription from the prgQ promoter into the pCF10 genes
      mediating conjugation functions; PrgX also positively regulates its own
      expression, as well as that of Qa. We found two DNA target sites for PrgX binding
      in the intergenic region between the prgX and prgQ genes of pCF10. The primary
      binding site near prgX includes an 11 bp palindromic sequence and showed
      relatively high affinity for His-tagged PrgX (His-PrgX). The secondary binding
      site is between the -35 and -10 regions of the prgQ promoter, and contains only a
      half of the palindromic sequence; this binding site showed weaker affinity. A
      region of pCF10 including the prgQ promoter and the secondary binding site
      reduced Qa RNA levels greatly and this reduction was overcome by the presence of
      the primary binding site and PrgX. In constructs where the binding sites were
      mutated individually or in combination, the intracellular levels of PrgX protein
      and Qa RNA were reduced significantly. On the basis of these results, we propose
      that both DNA binding sites are required for the autoregulation of PrgX
      expression and for positive regulation of Qa RNA.

PMID- 11827472
TI  - The intercalating beta-hairpin of T7 RNA polymerase plays a role in promoter DNA
      melting and in stabilizing the melted DNA for efficient RNA synthesis.
AB  - Phage T7 RNA polymerase contains within its single polypeptide all the elements
      for specific recognition and melting of its promoter DNA. Crystallographic
      studies indicate that a beta-hairpin (230-245) with an intercalating valine
      residue plays a role in promoter opening. We mutated V237 to several amino acids,
      deleted five amino acid residues at the tip of the hairpin, and mutated E242 and
      D240 at the base of the hairpin to define the roles of the tip and base of the
      hairpin in DNA strand separation. The affinity of the hairpin mutants for the
      promoter DNA was not significantly affected. Stopped-flow kinetic studies showed
      that the bimolecular rate of DNA binding and the observed rate of pre-initiation
      open complex formation that corresponds to the sum of DNA opening and closing
      steps were within 20 to 40 % of the wild-type polymerase. Yet, most mutants
      showed a smaller amount of the pre-initiation open complex at equilibrium,
      indicating that the individual rates of promoter opening and closing steps were
      altered in the mutants. The base mutants, E242A and D240A, showed both a lower
      rate of promoter opening and a higher rate of promoter closing, suggesting their
      role in stabilization of the open complex. The V237D and the deletion mutant
      showed mainly a lower rate of promoter opening, suggesting that the tip of the
      hairpin may nucleate DNA opening. The defect in pre-initiation open complex
      formation affected downstream steps such as the rate of the first phosphodiester
      bond formation step, but did not affect significantly the apparent K(d) of
      initiating GTPs. We propose that D240 and E242 anchor the hairpin to the DNA and
      position the tip of the hairpin to allow V237 to intercalate and distort the DNA
      during open complex formation. The interactions of E242 and D240 with the
      upstream junction of the melted dsDNA promoter also align the template strand
      within the active site for efficient RNA synthesis.

PMID- 11827473
TI  - Concerted binding and bending of DNA by Escherichia coli integration host factor.
AB  - Integration host factor (IHF) is a heterodimeric Escherichia coli protein that
      plays essential roles in a variety of cellular processes including site-specific
      recombination, transcription, and DNA replication. The IHF-DNA interface extends
      over three helical turns and includes sequential minor groove contacts that
      present strong, sequence specific protection patterns against hydroxyl radical
      cleavage. Synchrotron X-ray footprinting has been used to follow the kinetics of
      formation of DNA-protein contacts in the IHF-DNA complex with single base-pair
      spatial, and millisecond time, resolution. The three sites of IHF protection on
      the DNA develop with similar time-dependence, indicating that sequence specific
      binding and bending occur concertedly. Two distinct phases are observed in the
      association process. The first "burst" phase is characterized by a rate that is
      greater than diffusion limited (>10(10) s(-1) M(-1)) and the second phase is on
      the order of diffusion controlled (approximately 10(8) M(-1) s(-1)). The overall
      kinetics of association become faster with increasing IHF concentration showing
      that complex formation is second-order with protein. The rate of association is
      maximal between 100 and 200 mM KCl decreasing at higher and lower concentrations.
      The rate of IHF dissociation from site-specifically bound DNA increases
      monotonically as KCl concentration is increased. The dissociation progress curves
      are biphasic with the amplitude of the first phase dependent upon competitor DNA
      concentration. These results are the first analysis by synchrotron footprinting
      of the fast kinetics of a protein-DNA interaction and suggest that IHF binds its
      specific site through a multiple-step mechanism in which the first step is
      facilitated diffusion along the length of the duplex followed by subsequent
      binding and bending of the DNA in a concerted manner.

PMID- 11827474
TI  - Involvement of DNA polymerase beta in DNA replication and mutagenic consequences.
AB  - Overexpression in mammalian cells of the error-prone DNA polymerase beta (Pol
      beta) has been found to increase the spontaneous mutagenesis. Here, we
      investigated a possible mechanism used by Pol beta to be a genetic instability
      enhancer: its interference in replicative DNA synthesis, which is normally
      catalysed by the DNA polymerases alpha, delta and epsilon. By taking advantage of
      the ability to incorporate efficiently into DNA the chain terminator ddCTP as
      well as the oxidised nucleotide 8-oxo-dGTP, we show here that purified Pol beta
      can compete with the replicative DNA polymerases during replication in vitro of
      duplex DNA when added to human cell extracts. We found that involvement of Pol
      beta lowers replication fidelity and results in a modified error-specificity.
      Furthermore, we demonstrated that involvement of Pol beta occurred during
      synthesis of the lagging strand. These in vitro data provide one possible
      explanation of how overexpression of the enzyme could perturb the genetic
      instability in mammalian cells. We discuss these findings within the scope of the
      up-regulation of Pol beta in many cancer cells.

PMID- 11827475
TI  - Base-sequence specificity of Hoechst 33258 and DAPI binding to five (A/T)4 DNA
      sites with kinetic evidence for more than one high-affinity Hoechst 33258-AATT
      complex.
AB  - The binding of Hoechst 33258 and DAPI to five different (A/T)4 sequences in a
      stable DNA hairpin was studied exploiting the substantial increase in dye
      fluorescence upon binding. The two dyes have comparable affinities for the AATT
      site (e.g. association constant K(a)=5.5 x 10(8) M(-1) for DAPI), and their
      affinities decrease in the series AATT >> TAAT approximately equal to ATAT > TATA
      approximately equal to TTAA. The extreme values of K(a) differ by a factor of 200
      for Hoechst 33258 but only 30 for DAPI. The binding kinetics of Hoechst 33258
      were measured by stopped-flow under pseudo-first order conditions with an (A/T)4
      site in excess. The lower-resolution experiments can be well represented by
      single exponential processes, corresponding to a single-step binding mechanism.
      The calculated association-rate parameters for the five (A/T)4 sites are similar
      (2.46 x 10(8) M(-1) s(-1) to 0.86 x 10(8) M(-1) s(-1)) and nearly diffusion
      controlled, while the dissociation-rate parameters vary from 0.42 s(-1) to 96 s(
      1). Thus the association constants are kinetically controlled and are close to
      their equilibrium-determined values. However, when obtained with increased signal
      to-noise ratio, the kinetic traces for Hoechst 33258 binding at the AATT site
      reveal two components. The concentration dependencies of the two time constants
      and amplitudes are consistent with two different kinetically equivalent two-step
      models. In the first model, fast bimolecular binding is followed by an
      isomerization of the initial complex. In the second model, two single-step
      associations form two complexes that mutually exclude each other. For both models
      the four reaction-rate parameters are calculated. Finally, specific dissociation
      kinetics, using poly[d(A-5BrU)], show that the kinetics are even more complex
      than either two-step model. We correlate our results with the different binding
      orientations and locations of Hoechst 33258 in the DNA minor groove found in
      several structural studies in the literature.

PMID- 11827476
TI  - Towards proteome-wide production of monoclonal antibody by phage display.
AB  - Sequencing of the human genome reveals that there are approximately 30,000 genes
      that encode an even greater number of proteins which comprise the human proteome.
      Characterization of gene products at the genome-wide scale requires the
      development of high throughput methods to generate temporo-spatial information on
      each and every protein in the cell under normal and pathological conditions.
      Monoclonal antibodies are important reagents for these studies. We have developed
      a method to generate human monoclonal antibodies by selecting phage antibody
      libraries directly on antigen blotted onto poly(vinylidene fluoride) membranes.
      Cellular proteins are first separated by two dimensional (2D) gel
      electrophoresis, Western blotted onto poly(vinylidene fluoride) membranes, and
      used to select phage antibody libraries. Monoclonal antibodies can be generated
      against individual protein spots on a 2D gel. The antibodies are functional in
      Western blotting, ELISA, and immunohistochemistry. Automation of this process
      should allow high throughput production of monoclonal phage antibodies against
      cellular proteins as well as proteins that are uniquely expressed under
      pathological conditions.

PMID- 11827477
TI  - Three-dimensional structure by cryo-electron microscopy of YvcC, an homodimeric
      ATP-binding cassette transporter from Bacillus subtilis.
AB  - YvcC, a multidrug transporter from Bacillus subtilis, is a member of the ATP
      binding cassette superfamily, highly homologous to each half of human multidrug
      resistance P-glycoprotein and to several other bacterial half-ABC transporters.
      Here, the purified recombinant histidine-tagged YvcC has been reconstituted into
      a lipid bilayer. Controlled and partial detergent removal from YvcC-lipid
      micelles allowed the production of particularly interesting lipid-detergent-YvcC
      ring-shaped particles, about 40 nm in diameter, well suited for single particle
      analysis by cryo-electron microscopy. Furthermore, binding of these histidine
      tagged ring-shaped particles to lipid layers functionalized with a Ni(2+)
      chelating head group generated a preferential perpendicular orientation,
      eliminating the missing cone in the final three-dimensional reconstruction. From
      such analysis, a computed volume has been determined to 2.5 nm resolution giving
      a detailed insight into the structural organization of this half-ABC transporter
      within a membrane. The repetitive unit in the ring-shaped particles is consistent
      with a homodimeric organization of YvcC. Each subunit was composed of three
      domains: a 5 nm height transmembrane region, a stalk of about 4 nm in height and
      2 nm in diameter, and a cytoplasmic lobe of about 5-6 nm in diameter. The latest
      domain, which fitted with the reported X-ray structure of HisP, was identified as
      the nucleotide-binding domain (NBD). The 3D reconstruction of the YvcC homodimer
      well compared with the very recent X-ray crystallographic data on the MsbA
      homodimer from Escherichia coli, supporting the existence of a central open
      chamber between the two subunits constituting the homodimer. In addition, the 3D
      reconstruction of YvcC embedded in a membrane revealed an asymmetric organization
      of the two NBDs sites within the homodimer, as well as a dimeric interaction
      between two homodimers.

PMID- 11827478
TI  - Selection of large diversities of antiidiotypic antibody fragments by phage
      display.
AB  - Antiidiotypic antibodies (Ab2) are needed as tools for a better understanding of
      molecular mimicry and the immunological network, and for many potential
      applications in the biomedical and pharmaceutical field. Antiidiotypic antibodies
      mimicking carbohydrate or conformational epitopes (Ab2beta) are of considerable
      interest as surrogate immunogens for cancer vaccination. However, it has so far
      been difficult and tedious to produce Ab2s to a given antigen. Here we describe a
      fast and reliable technique for generating large diversities of antiidiotypic
      single chain antibody fragments from non-immunized phagemid libraries using phage
      display. Key elements are a specific elution with the original antigen followed
      by trypsin treatment of the eluted phages in combination with the protease
      sensitive helperphage KM13. This novel method was compared with various
      conventional selection and elution methods, including, specific elution with or
      without trypsin treatment, elution with glycine at pH 2.2 with or without trypsin
      treatment, and elution by trypsin treatment only. The results clearly show that
      specific elution in combination with trypsin treatment of the eluted phages is by
      far superior to the other conventional methods, enabling for the first time the
      generation of a large variety of Ab2s after only two to three rounds of
      selection, thereby maintaining maximum diversity. We obtained 28 to 88
      antiidiotypes out of 96 tested clones after two to three rounds of selection with
      a diversity of 55-90 %. This was achieved for two carbohydrate (di-, and
      tetrasaccharides) and one conformational protein epitope using two large naive
      libraries and their corresponding monoclonal Ab1. The antiidiotypic nature of the
      selected scFv-phages was verified by ELISA and immunocytochemistry inhibition
      experiments.

PMID- 11827479
TI  - Sugar specificity of bacterial CMP kinases as revealed by crystal structures and
      mutagenesis of Escherichia coli enzyme.
AB  - Bacterial cytidine monophosphate (CMP) kinases are characterised by an insert
      enlarging their CMP binding domain, and by their particular substrate
      specificity. Thus, both CMP and 2'-deoxy-CMP (dCMP) are good phosphate acceptors
      for the CMP kinase from Escherichia coli (E. coli CMPK), whereas eukaryotic
      UMP/CMP kinases phosphorylate the deoxynucleotides with very low efficiency. Four
      crystal structures of E. coli CMPK complexed with nucleoside monophosphates
      differing in their sugar moiety were solved. Both structures with CMP or dCMP
      show interactions with the pentose that were not described so far. These
      interactions are lost with the poorer substrates AraCMP and 2',3'-dideoxy-CMP.
      Comparison of all four structures shows that the pentose hydroxyls are involved
      in ligand-induced movements of enzyme domains. It also gives a structural basis
      of the mechanism by which either ribose or deoxyribose can be accommodated. In
      parallel, for the four nucleotides the kinetic results of the wild-type enzyme
      and of three structure-based variants are presented. The phosphorylation rate is
      significantly decreased when either of the two pentose interacting residues is
      mutated. One of these is an arginine that is highly conserved in all known
      nucleoside monophosphate kinases. In contrast, the other residue, Asp185, is
      typical of bacterial CMP kinases. It interacts with Ser101, the only residue
      conserved in all CMP binding domain inserts. Mutating Ser101 reduces CMP
      phosphorylation only moderately, but dramatically reduces dCMP phosphorylation.
      This is the first experimental evidence of a catalytic role involving the
      characteristic insert of bacterial CMP kinases. Furthermore, this role concerns
      only dCMP phosphorylation, a feature of this family of enzymes.

PMID- 11827480
TI  - Crystal structure of the soluble domain of the major anaerobically induced outer
      membrane protein (AniA) from pathogenic Neisseria: a new class of copper
      containing nitrite reductases.
AB  - The major anaerobically induced outer membrane protein (AniA) from pathogenic
      Neisseria gonorrhoeae is essential for cell growth under oxygen limiting
      conditions in the presence of nitrite and is protective against killing by human
      sera. A phylogenic analysis indicates that AniA is a member of a new class of
      copper-containing nitrite reductases. Expression of the soluble domain of AniA
      yields a protein capable of reducing nitrite with specific activity of 160
      units/mg, approximately 50 % of that measured for the nitrite reductase from the
      strong soil denitrifier Alcaligenes faecalis S-6. The crystal structure of the
      soluble domain of AniA was solved by molecular replacement and sixfold averaging
      to a resolution of 2.4 A. The nitrite soaked AniA crystal structure refined to
      1.95 A reveals a bidentate mode of substrate binding to the type II copper.
      Despite low sequence identity (approximately 30 %), the core cupredoxin fold of
      AniA is similar to that found in copper-containing nitrite reductases from soil
      bacteria. The main structural differences are localized to two attenuated surface
      loops that map to deletions in the sequence alignment. In soil nitrite
      reductases, one of these surface loops is positioned near the type I copper site
      and contributes residues to the docking surface for proteaceous electron donors.
      In AniA, the attenuation of this loop results in a restructured hydrophobic
      binding surface that may be required to interact with a lipid anchored azurin.
      The second attenuated loop is positioned on the opposite side of AniA and may
      facilitate a more intimate interaction with the lipid membrane. A unique
      combination of structural effectors surrounding the type I copper site of sAnia
      contribute to a unusual visible absorption spectra with components observed
      previously in either green or blue type I copper sites.

PMID- 11827481
TI  - Structure and mechanism of action of a cofactor-dependent phosphoglycerate mutase
      homolog from Bacillus stearothermophilus with broad specificity phosphatase
      activity.
AB  - The crystal structure of Bacillus stearothermophilus PhoE (originally termed
      YhfR), a broad specificity monomeric phosphatase with a molecular mass of
      approximately 24 kDa, has been solved at 2.3 A resolution in order to investigate
      its structure and function. PhoE, already identified as a homolog of a cofactor
      dependent phosphoglycerate mutase, shares with the latter an alpha/beta/alpha
      sandwich structure spanning, as a structural excursion, a smaller subdomain
      composed of two alpha-helices and one short beta-strand. The active site contains
      residues from both the alpha/beta/alpha sandwich and the sub-domain. With the
      exception of the hydrophilic catalytic machinery conserved throughout the
      cofactor-dependent phosphoglycerate mutase family, the active-site cleft is
      strikingly hydrophobic. Docking studies with two diverse, favored substrates show
      that 3-phosphoglycerate may bind to the catalytic core, while alpha
      napthylphosphate binding also involves the hydrophobic portion of the active-site
      cleft. Combining a highly favorable phospho group binding site common to these
      substrate binding modes and data from related enzymes, a catalytic mechanism can
      be proposed that involves formation of a phosphohistidine intermediate on His10
      and likely acid-base behavior of Glu83. Other structural factors contributing to
      the broad substrate specificity of PhoE can be identified. The dynamic
      independence of the subdomain may enable the active-site cleft to accommodate
      substrates of different sizes, although similar motions are present in
      simulations of cofactor-dependent phosphoglycerate mutases, perhaps favoring a
      more general functional role. A significant number of entries in protein sequence
      databases, particularly from unfinished microbial genomes, are more similar to
      PhoE than to cofactor-dependent phosphoglycerate mutases or to fructose-2,6
      bisphosphatases. This PhoE structure will therefore serve as a valuable basis for
      inference of structural and functional characteristics of these proteins.

PMID- 11827482
TI  - Crystal structure of extracellular human BAFF, a TNF family member that
      stimulates B lymphocytes.
AB  - B cell activating factor (BAFF), a ligand belonging to the tumor necrosis factor
      (TNF) family, plays a critical role in regulating survival and activation of
      peripheral B cell populations and has been associated with autoimmune disease.
      BAFF is known to interact with three receptors, BCMA, TACI and BAFF-R, that have
      distant similarities with other receptors of the TNF family. We have determined
      the crystal structure of the TNF-homologous domain of BAFF at 2.8 A resolution.
      The structure reveals significant differences when compared to other TNF family
      members, including an unusually long D-E loop that participates in the formation
      of a deep, concave and negatively charged region in the putative receptor binding
      site. The BAFF structure was further used to generate a homology model of APRIL,
      a closely related TNF family ligand that also binds to BCMA and TACI, but not
      BAFF-R. Analysis of the putative receptor binding sites of BAFF and APRIL
      suggests that differences in the D-E loop structure and electrostatic surface
      potentials may be important for determining binding specificities for BCMA, TACI
      and BAFF-R.

PMID- 11827483
TI  - Atomic resolution structures of oxidized [4Fe-4S] ferredoxin from Bacillus
      thermoproteolyticus in two crystal forms: systematic distortion of [4Fe-4S]
      cluster in the protein.
AB  - Diffraction data of two crystal forms (forms I and II) of [4Fe-4S] ferredoxin
      from Bacillus thermoproteolyticus have been collected to 0.92 A and 1.00 A
      resolutions, respectively, at 100 K using synchrotron radiation. Anisotropic
      temperature factors were introduced for all non-hydrogen atoms in the refinement
      with SHELX-97, in which stereochemical restraints were applied to the protein
      chain but not to the [4Fe-4S] cluster. The final crystallographic R-factors are
      9.8 % for 7.0-0.92 A resolution data of the form I and 11.2 % for the 13.3-1.0 A
      resolution data of the form II. Many hydrogen atoms as well as multiple
      conformations for several side-chains have been identified. The present
      refinement has revised the conformations of several peptide bonds and side-chains
      assigned previously at 2.3 A resolution; the largest correction was that the main
      chain of Pro1 and the side-chain of Lys2 were changed by rotating the C(alpha)-C
      bond of Lys2. Although the overall structures in the two crystal forms are very
      similar, conformational differences are observed in the two residues at the
      middle (Glu29 and Asp30) and the C-terminal residues, which have large
      temperature factors. The [4Fe-4S] cluster is a distorted cube with non-planar
      rhombic faces. Slight but significant compression of the four Fe-S bonds along
      one direction is observed in both crystal forms, and results in the D(2d)
      symmetry of the cluster. The compressed direction of the cluster relative to the
      protein is conserved in the two crystal forms and consistent with that in one of
      the clusters in Clostridium acidurici ferredoxin.

PMID- 11827484
TI  - Crystal structures of the SH2 domain of Grb2: highlight on the binding of a new
      high-affinity inhibitor.
AB  - The activation of growth factor receptors induces phosphorylation of tyrosine
      residues in its C-terminal part, creating binding sites for SH2 domain-containing
      proteins. Grb2 is a protein that recruits Sos, the exchange factor for Ras.
      Recruitment of Sos allows for Ras activation and subsequent signal transmission.
      This promotes translocation of MAP kinases into the nucleus and activation of
      early transcription factors. Grb2, a 25 kDa protein, is composed of one SH2
      domain surrounded by two SH3 domains. The SH2 domain of Grb2 binds to class II
      phosphotyrosyl peptides with the consensus sequence pYXNX. Thus, Grb2 is a good
      example of a bifunctional adaptor protein that brings proteins into close
      proximity, allowing signal transduction through proteins located in different
      compartments. To explore the interactions between Grb2 and phosphorylated
      ligands, we have solved the crystal structure of complexes between the Grb2-SH2
      domain and peptides corresponding to Shc-derived sequences. Two structures are
      described: the Grb2-SH2 domain in complex with PSpYVNVQN at 1.5 A; and the Grb2
      SH2 domain in complex with mAZ*-pY-(alphaMe)pY-N-NH2 pseudo-peptide, at 2 A. Both
      are compared to an unliganded SH2 structure determined at 2.7 A which,
      interestingly enough, forms a dimer through two swapping subdomains from two
      symmetry-related molecules. The nanomolar affinity of the mAZ-pY-(alphaMe)pY-N
      NH2 pseudo-peptide for Grb2-SH2 is related to new interactions with non-
      conserved residues. The design of Grb2-SH2 domain inhibitors that prevent
      interaction with tyrosine kinase proteins or other adaptors like Shc or IRS1
      should provide a means to interrupt the Ras signaling pathway. Newly synthesized
      pseudo-peptides exhibit nanomolar affinities for the Grb2-SH2 domain. It will
      then be possible to design new inhibitors with similar affinity and simpler
      chemical structures.

PMID- 11827485
TI  - Low resolution solution structure of the Apo form of Escherichia coli haemoglobin
      protease Hbp.
AB  - We have studied the solution properties of the apo form of the haemoglobin
      protease or "haemoglobinase", Hbp, a principal component of an important iron
      acquisition system in pathogenic Escherichia coli. Experimental determination of
      secondary structure content from circular dichroism (CD) spectroscopy, obtained
      using synchrotron light, showed that the protein contains predominately beta
      sheets in agreement with secondary structure prediction from the primary
      sequence. Next, the size and shape of the protein were probed using analytical
      ultracentrifugation (AUC) and small angle X-ray scattering (SAXS). These showed
      that Hbp is a monomer, with an extended conformation. Using ab initio
      reconstruction methods we have produced a model of Hbp, which shows that the
      protein adopts an extended crescent-shaped conformation. Analysis of the
      resulting model gives hydrodynamic parameters in good agreement with those
      observed experimentally. Thus we are able to construct a hydrodynamically
      rigorous model of apo-Hbp in solution, not only giving a greater level of
      confidence to the results of the SAXS reconstruction methods, but providing the
      first three-dimensional view of this intriguing molecule.

PMID- 11827486
TI  - The structure of porcine parvovirus: comparison with related viruses.
AB  - The structure of baculovirus-expressed porcine parvovirus (PPV) capsids was
      solved using X-ray crystallography and was found to be similar to the related
      canine parvovirus (CPV) and minute virus of mice (MVM). The PPV capsid protein
      has 57 % and 49 % amino acid sequence identity with CPV and MVM, respectively,
      but the degree of conservation of surface-exposed residues is lower than average.
      Consequently, most of the structural differences are on the surface and are the
      probable cause of the known variability in antigenicity and host range. The NADL
      2 and Kresse strains of PPV have distinct tissue tropisms and pathogenicity,
      which are mediated by one or more of the amino acid residues 381, 386, and 436.
      These residues are on or near the surface of the virus capsid, where they are
      likely to be associated with virus-cell interactions.

PMID- 11827487
TI  - Analysis of the E. coli NifS CsdB protein at 2.0 A reveals the structural basis
      for perselenide and persulfide intermediate formation.
AB  - The Escherichia coli NifS CsdB protein is a member of the homodimeric pyridoxal
      5'-phosphate (PLP)-dependent family of enzymes. These enzymes are capable of
      decomposing cysteine or selenocysteine into L-alanine and sulfur or selenium,
      respectively. E. coli NifS CsdB has a high specificity for L-selenocysteine in
      comparison to l-cysteine, suggesting a role for this enzyme is selenium
      metabolism. The 2.0 A crystal structure of E. coli NifS CsdB reveals a high
      resolution view of the active site of this enzyme in apo-, persulfide,
      perselenide, and selenocysteine-bound intermediates, suggesting a mechanism for
      the stabilization of the enzyme persulfide and perselenide intermediates during
      catalysis, a necessary intermediate in the formation of sulfur and selenium
      containing metabolites.

PMID- 11827488
TI  - Crystal structure reveals basis for the inhibitor resistance of human brain
      trypsin.
AB  - Severe neurodegradative brain diseases, like Alzheimer, are tightly linked with
      proteolytic activity in the human brain. Proteinases expressed in the brain, such
      as human trypsin IV, are likely to be involved in the pathomechanism of these
      diseases. The observation of amyloid formed in the brain of transgenic mice
      expressing human trypsin IV supports this hypothesis. Human trypsin IV is also
      resistant towards all studied naturally occurring polypeptide inhibitors. It has
      been postulated that the substitution of Gly193 to arginine is responsible for
      this inhibitor resistance. Here we report the X-ray structure of human trypsin IV
      in complex with the inhibitor benzamidine at 1.7 A resolution. The overall fold
      of human trypsin IV is similar to human trypsin I, with a root-mean square
      deviation of only 0.5 A for all C(alpha) positions. The crystal structure reveals
      the orientation of the side-chain of Arg193, which occupies an extended
      conformation and fills the S2' subsite. An analysis of surface electrostatic
      potentials shows an unusually strong clustering of positive charges around the
      primary specificity pocket, to which the side-chain of Arg193 also contributes.
      These unique features of the crystal structure provide a structural basis for the
      enhanced inhibitor resistance, and enhanced substrate restriction, of human
      trypsin IV.

PMID- 11827489
TI  - Solution structure of the eukaryotic pore-forming cytolysin equinatoxin II:
      implications for pore formation.
AB  - Sea anemones produce a family of 18-20 kDa proteins, the actinoporins, that lyse
      cells by forming pores in cell membranes. Sphingomyelin plays an important role
      in their lytic activity, with membranes lacking this lipid being largely
      refractory to these toxins. The structure of the actinoporin equinatoxin II in
      aqueous solution, determined from NMR data, consists of two short helices packed
      against opposite faces of a beta-sandwich structure formed by two five-stranded
      beta-sheets. The protein core has extensive hydrophobic interfaces formed by
      residues projecting from the internal faces of the two beta-sheets. 15N
      relaxation data show uniform backbone dynamics, implying that equinatoxin II in
      solution is relatively rigid, except at the N terminus; its inferred rotational
      correlation time is consistent with values for monomeric proteins of similar
      mass. Backbone amide exchange rate data also support the view of a stable
      structure, even though equinatoxin II lacks disulfide bonds. As monitored by NMR,
      it unfolds at around 70 degrees C at pH 5.5. At 25 degrees C the structure is
      stable over the pH range 2.5-7.3 but below pH 2.5 it undergoes a slow transition
      to an incompletely unfolded structure resembling a molten globule. Equinatoxin II
      has two significant patches of positive electrostatic potential formed by surface
      exposed Lys and Arg residues, which may assist its interaction with charged
      regions of the lipid head groups. Tyr and Trp residues on the surface may also
      contribute by interacting with the carbonyl groups of the acyl chains of target
      membranes. Data from mutational studies and truncated analogues identify two
      regions of the protein involved in membrane interactions, the N-terminal helix
      and the Trp-rich region. Once the protein is anchored, the N-terminal helix may
      penetrate the membrane, with up to four helices lining the pore, although other
      mechanisms of pore formation cannot be ruled out.

PMID- 11827490
TI  - Burst-phase expansion of native protein prior to global unfolding in SDS.
AB  - Although numerous studies have been directed at understanding early folding
      events through the characterization of folding intermediates, there are few
      reports on the very late folding events, i.e. on the events taking place on the
      native side of the folding barrier and on alternative conformations of the folded
      state. To shed further light on these issues, we have characterized by protein
      engineering the structure of an expanded but native-like intermediate that
      accumulates transiently in the unfolding reaction of the small protein S6 in the
      presence of SDS. The results show that the SDS micelles attack the native protein
      in the dead-time of the denaturation experiment, causing an expansion of the
      hydrophobic core prior to the major unfolding transition. We distinguish two
      forms of the unfolding intermediate that are correlated with the micellar
      structure. With spherical micelles, the expansion is seen mainly as a weakening
      of the interactions which anchor the two alpha-helices to the core of the S6
      structure. With cylindrical micelles, prevalent at higher SDS concentrations, the
      expansion is more global and produces a species which closely resembles the
      transition-state structure for unfolding in GdmCl. Despite the highly weakened
      core, the micelle-associated intermediate displays cooperative unfolding,
      indicating a significant structural plasticity of the species on the native side
      of the folding barrier in the presence of SDS.

PMID- 11827491
TI  - Binding of prion protein to lipid membranes and implications for prion
      conversion.
AB  - The binding of the Syrian hamster prion protein, SHaPrP(90-231), to model lipid
      membranes was investigated by tryptophan fluorescence. Membranes composed of
      negatively charged or zwitterionic lipids, and raft-like membranes containing
      dipalmitoylphosphatidylcholine(1,2-dipalmitoyl-sn-glycero-3-phosphocholine
      (DPPC), cholesterol and sphingomyelin, were investigated. It was found that
      SHaPrP(90-231) binds to negatively charged lipid membranes and raft-like
      membranes. Binding of PrP to negatively charged lipid membranes involves both
      electrostatic and hydrophobic lipid-protein interactions and results in partial
      insertion of PrP into the lipid bilayer. This membrane-inserted conformation of
      PrP is richer in beta-sheet structure and has a disruptive effect on the
      integrity of the lipid bilayer, leading to total release of vesicle contents. In
      contrast, the binding of PrP to raft-like membranes is driven by hydrophobic
      lipid-protein interactions and induces the formation of alpha-helical structure.
      This conformation of PrP with a high content of alpha-helix is formed only at pH
      7 and does not destabilize the lipid bilayer. Our findings support the view that
      an interaction of PrP with lipid membranes could play a role in PrP conversion.

PMID- 11827492
TI  - Within the twilight zone: a sensitive profile-profile comparison tool based on
      information theory.
AB  - This paper presents a novel approach to profile-profile comparison. The method
      compares two input profiles (like those that are generated by PSI-BLAST) and
      assigns a similarity score to assess their statistical similarity. Our profile
      profile comparison tool, which allows for gaps, can be used to detect weak
      similarities between protein families. It has also been optimized to produce
      alignments that are in very good agreement with structural alignments. Tests show
      that the profile-profile alignments are indeed highly correlated with
      similarities between secondary structure elements and tertiary structure.
      Exhaustive evaluations show that our method is significantly more sensitive in
      detecting distant homologies than the popular profile-based search programs PSI
      BLAST and IMPALA. The relative improvement is the same order of magnitude as the
      improvement of PSI-BLAST relative to BLAST. Our new tool often detects
      similarities that fall within the twilight zone of sequence similarity.

PMID- 11827493
TI  - Alcohol consumption and risk for congestive heart failure in the Framingham Heart
      Study.
AB  - BACKGROUND: Although excessive alcohol consumption can promote cardiomyopathy,
      little is known about the association between alcohol consumption and risk for
      congestive heart failure in the community. OBJECTIVE: To determine the relation
      between alcohol consumption and risk for congestive heart failure in the
      community. DESIGN: Community-based, prospective observational study. SETTING:
      Framingham, Massachusetts. PARTICIPANTS: Participants in the Framingham Heart
      Study who were free of congestive heart failure and coronary heart disease.
      MEASUREMENTS: Self-reported alcohol consumption; sex-specific rates of congestive
      heart failure per 1000 person-years of follow-up by level of alcohol consumption.
      RESULTS: In men, 99 cases of congestive heart failure occurred during 26 035
      person-years of follow-up. In women, 120 cases of congestive heart failure
      occurred during 35 563 person-years of follow-up. After adjustment for multiple
      confounders, risk for congestive heart failure was lower among men at all levels
      of alcohol consumption compared with men who consumed less than 1 drink/wk. The
      hazard ratio for congestive heart failure was lowest among men who consumed 8 to
      14 drinks/wk (0.41 [95% CI, 0.21 to 0.81]) compared with those who consumed less
      than 1 drink/wk. In women, the age-adjusted hazard ratio for congestive heart
      failure was lowest among those who consumed 3 to 7 drinks/wk (0.49 [CI, 0.25 to
      0.96]) compared with those who consumed less than 1 drink/wk. However, after
      adjustment for multiple predictors of congestive heart failure, this association
      was no longer statistically significant. CONCLUSIONS: In the community, alcohol
      consumption is not associated with increased risk for congestive heart failure,
      even among heavy drinkers (> or = 15 drinks/wk in men and > or = 8 drinks/wk in
      women). To the contrary, when consumed in moderation, alcohol appears to protect
      against congestive heart failure.

PMID- 11827495
TI  - The effect of controlled drinking in alcoholic cardiomyopathy.
AB  - BACKGROUND: Cardiomyopathy is a potentially fatal complication of alcohol abuse.
      In alcoholic persons who develop cardiac dysfunction, abstinence is thought to be
      essential to halt further deterioration of cardiac contractility. Some evidence
      indicates that reducing alcohol intake may also be beneficial. OBJECTIVE: To
      evaluate the effect of moderate "controlled" drinking on cardiac function in
      patients with alcoholic cardiomyopathy. DESIGN: 4-year prospective cohort study.
      SETTING: A university hospital in Barcelona, Spain. PATIENTS: 55 alcoholic men
      with cardiomyopathy who had been drinking a minimum of 100 g of ethanol per day
      for at least 10 years. MEASUREMENTS: Evaluation of ethanol intake and nutrition,
      clinical assessment of cardiac status, and sequential echocardiography and
      radionuclide cardiac angiography. RESULTS: After the first year of evaluation,
      all patients with cardiomyopathy who abstained from alcoholic beverages
      demonstrated significant improvement in left ventricular function (average
      increase in left ventricular ejection fraction, 0.131 [95% CI, 0.069 to 0.193]).
      Patients who drank 20 to 60 g of ethanol per day showed a comparable mean
      improvement of 0.125 (CI, 0.082 to 0.168). In contrast, left ventricular ejection
      fraction deteriorated further in most patients who continued to abuse alcohol
      (>80 g/d). After 4 years, left ventricular ejection fraction had continued to
      improve in both abstinent patients and those who controlled their drinking. Ten
      patients who had continued to consume more than 80 g of ethanol per day died
      during the study. CONCLUSION: In patients with alcoholic cardiomyopathy, both
      abstinence and controlled drinking of up to 60 g of ethanol per day (four
      standard drinks) were comparably effective in promoting improvement in cardiac
      function.

PMID- 11827496
TI  - Dietary patterns and risk for type 2 diabetes mellitus in U.S. men.
AB  - BACKGROUND: The role of diet in the development of type 2 diabetes mellitus
      remains unsettled. OBJECTIVE: To examine the association between major dietary
      patterns and risk for type 2 diabetes mellitus. DESIGN: Prospective cohort study.
      SETTING: United States. PARTICIPANTS: 42 504 male health professionals, 40 to 75
      years of age, without diagnosed diabetes, cardiovascular disease, or cancer at
      baseline. MEASUREMENTS: Using factor analysis based on data from food-frequency
      questionnaires, we identified and validated two major dietary patterns that we
      labeled "prudent" (characterized by higher consumption of vegetables, fruit,
      fish, poultry and whole grains) and "western" (characterized by higher
      consumption of red meat, processed meat, French fries, high-fat dairy products,
      refined grains, and sweets and desserts). Relative risks and 95% CIs were
      adjusted for potential confounders, including body mass index (BMI), physical
      activity, and cigarette smoking. RESULTS: During 12 years of follow-up (466 508
      person-years), we documented 1321 cases of type 2 diabetes. The prudent dietary
      pattern score was associated with a modestly lower risk for type 2 diabetes
      (relative risk for extreme quintiles, 0.84 [CI, 0.70 to 1.00]). In contrast, the
      western dietary pattern score was associated with an increased risk for type 2
      diabetes (relative risk, 1.59 [CI, 1.32 to 1.93]; P < 0.001 for trend). A high
      score for the western dietary pattern combined with low physical activity
      (relative risk comparing extreme quintiles of dietary pattern score and physical
      activity, 1.96 [CI, 1.35 to 2.84]) or obesity (relative risk for BMI > or = 30
      kg/m2 vs. <25 kg/m2, 11.2 [CI, 8.07 to 15.6]) was associated with a particularly
      high risk for type 2 diabetes. CONCLUSION: Our findings suggest that a western
      dietary pattern is associated with a substantially increased risk for type 2
      diabetes in men.

PMID- 11827497
TI  - Delayed-onset heparin-induced thrombocytopenia.
AB  - BACKGROUND: Heparin-induced thrombocytopenia presents 5 to 12 days after heparin
      exposure, with or without arterial or venous thromboemboli. Delayed recognition
      and treatment of heparin-induced thrombocytopenia contribute to poor patient
      outcomes. OBJECTIVE: To describe and increase awareness of a clinical scenario in
      which the onset or manifestations of heparin-induced thrombocytopenia are
      delayed. DESIGN: Retrospective case series. SETTING: Three large urban hospitals
      (with active cardiovascular surgery programs). PATIENTS: 14 patients seen over a
      3-year period in whom heparin-induced thrombocytopenia became apparent on delayed
      presentation with thromboembolic complications. MEASUREMENTS: Platelet counts,
      onset of objectively determined thromboembolism, results of heparin-induced
      platelet factor 4 antibody tests, and outcomes. RESULTS: Patients went home after
      hospitalizations that had included heparin exposure--in most cases, with no
      thrombocytopenia recognized--only to return to the hospital (median, day 14) with
      thromboembolic complications. Thromboemboli were venous (12 patients, 7 with
      pulmonary emboli) or arterial (4 patients) or both. Platelet counts were mildly
      decreased in all but 2 patients on second presentation. On readmission, 11
      patients received therapeutic heparin, which worsened the patients' clinical
      condition and, in all 11 cases, decreased the platelet count (mean at
      readmission, 143 x 10(9) cells/L; mean nadir after heparin re-exposure, 39 x
      10(9) cells/L). Results of serologic tests for heparin-induced antibodies were
      positive in all patients. Subsequent treatments included alternative
      anticoagulants (11 patients), thrombolytic drugs (3 patients), inferior vena cava
      filters (3 patients) and, eventually, warfarin (11 patients). Three patients
      died. CONCLUSIONS: Delayed-onset heparin-induced thrombocytopenia is increasingly
      being recognized. To avoid disastrous outcomes, physicians must consider heparin
      induced thrombocytopenia whenever a recently hospitalized patient returns with
      thromboembolism; therapy with alternative anticoagulants, not heparin, should be
      initiated.

PMID- 11827498
TI  - Chiropractic: a profession at the crossroads of mainstream and alternative
      medicine.
AB  - Chiropractic is a large and well-established health care profession in the United
      States. In this overview, we briefly examine the development of chiropractic from
      humble and contentious beginnings to its current state at the crossroads of
      alternative and mainstream medicine. Chiropractic has taken on many of the
      attributes of an established profession, improving its educational and licensing
      systems and substantially increasing its market share in the past two decades.
      The public increasingly uses chiropractic largely for spinal pain syndromes and
      appears to be highly satisfied with the results. Of all the so-called alternative
      professions, chiropractic has made the largest inroads into private and public
      health care financing systems and is increasingly viewed as an effective
      specialty by many in the medical profession. Much of the positive evolution of
      chiropractic can be ascribed to a quarter century-long research effort focused on
      the core chiropractic procedure of spinal manipulation. This effort has helped
      bring spinal manipulation out of the investigational category to become one of
      the most studied forms of conservative treatment for spinal pain. Chiropractic
      theory is still controversial, but recent expansion in federal support of
      chiropractic research bodes well for further scientific development. The medical
      establishment has not yet fully accepted chiropractic as a mainstream form of
      care. The next decade should determine whether chiropractic maintains the
      trappings of an alternative health care profession or becomes fully integrated
      into all health care systems.

PMID- 11827499
TI  - Evaluation and management of HIV-infected women.
AB  - The rate of newly diagnosed AIDS in the United States is increasing fastest in
      women, who are infected with HIV primarily through heterosexual transmission.
      Approximately 60% of these women are African American, and 18% are Latina. A
      gynecologic infection is the most common symptom that leads to initial medical
      evaluation. Specific studies at baseline should include CD4 lymphocyte count, HIV
      1 RNA level, and gynecologic examination with Papanicolaou smear. Decisions about
      initiation of antiretroviral therapy depend on the patient's clinical diagnoses,
      her willingness to adhere to treatment, and CD4 lymphocyte and HIV-1 RNA levels.
      Levels of HIV-1 RNA may be somewhat lower in women than in men at the same CD4
      count, whereas women have higher CD4 lymphocyte counts at the time of AIDS
      diagnosis. However, prospective trials have not yet indicated the need to change
      the threshold CD4 lymphocyte counts or HIV-RNA levels for initiation of therapy
      in women. The efficacy of antiretroviral therapy appears to be similar in men and
      women, although women are more likely to experience toxicities. Abnormal
      Papanicolaou smears occur in approximately 40% of women at baseline, and 58% are
      infected with human papillomavirus. The prevalence of both conditions increases
      with lower CD4 lymphocyte counts and higher HIV-1 RNA levels. Precursor lesions
      to cervical cancer may be effectively treated, but almost 50% recur within 1
      year, mandating careful follow-up. Referral should be sought for specialized
      gynecologic care and for issues related to HIV itself, since survival is
      prolonged in patients treated by physicians who are experienced in treating HIV.
      When they are provided the same access to care, HIV-infected women have similar
      prognoses as HIV-infected men.

PMID- 11827500
TI  - Medical professionalism in the new millennium: a physician charter.

PMID- 11827501
TI  - Stirred, not shaken.

PMID- 11827502
TI  - On being a doctor. Emergency.

PMID- 11827503
TI  - Sponsorship, authorship, and accountability.

PMID- 11827506
TI  - Low-dose thiazide and bone density.

PMID- 11827504
TI  - Sponsorship, authorship, and accountability.

PMID- 11827510
TI  - The landscape and lexicon of blinding in randomized trials.

PMID- 11827513
TI  - Nitrosocyanin, a red cupredoxin-like protein from Nitrosomonas europaea.
AB  - Nitrosocyanin (NC), a soluble, red Cu protein isolated from the ammonia-oxidizing
      autotrophic bacterium Nitrosomonas europaea, is shown to be a homo-oligomer of 12
      kDa Cu-containing monomers. Oligonucleotides based on the amino acid sequence of
      the N-terminus and of the C-terminal tryptic peptide were used to sequence the
      gene by PCR. The translated protein sequence was significantly homologous with
      the mononuclear cupredoxins such as plastocyanin, azurin, or rusticyanin, the
      type 1 copper-binding region of nitrite reductase, and the binuclear CuA binding
      region of N(2)O reductase or cytochrome oxidase. The gene for NC contains a
      leader sequence indicating a periplasmic location. Optical bands for the red Cu
      center at 280, 390, 500, and 720 nm have extinction coefficients of 13.9, 7.0,
      2.2, and 0.9 mM(-1), respectively. The reduction potential of NC (85 mV vs SHE)
      is much lower than those for known cupredoxins. Sequence alignments with
      homologous blue copper proteins suggested copper ligation by Cys95, His98,
      His103, and Glu60. Ligation by these residues (and a water), a trimeric protein
      structure, and a cupredoxin beta-barrel fold have been established by X-ray
      crystallography of the protein [Lieberman, R. L., Arciero, D. M., Hooper, A. B.,
      and Rosenzweig, A. C. (2001) Biochemistry 40, 5674-5681]. EPR spectra of the red
      copper center indicated a Cu(II) species with a g(parallel) of 2.25 and an
      A(parallel) of 13.8 mT (144 x 10(-4) cm(-1)), typical of Cu in a type 2 copper
      environment. NC is the first example of a type 2 copper center in a cupredoxin
      fold. The open coordination site and type 2 copper suggest a possible catalytic
      rather than electron transfer function.

PMID- 11827514
TI  - Mechanism of formation of a productive molten globule form of barstar.
AB  - Structural analysis of the initial steps in protein folding is difficult because
      of the swiftness with which these steps occur. Hence, the link between initial
      polypeptide chain collapse and formation of secondary and other specific
      structures remains poorly understood. Here, an equilibrium model has been
      developed for characterizing the initial steps of folding of the small protein
      barstar, which lead to the formation of a productive molten globule in the
      folding pathway. In this model, the high-pH-unfolded form (D form) of barstar,
      which is shown to be as unstructured as the urea-denatured form, is transformed
      progressively into a molten globule B form by incremental addition of the salt
      Na(2)SO(4) at pH 12. At very low concentrations of Na(2)SO(4), the D form
      collapses into a pre-molten globule (P) form, whose volume exceeds that of the
      native (N) state by only 20%, and which lacks any specific structure as
      determined by far- and near-UV circular dichroism. At higher concentrations of
      Na(2)SO(4), the P form transforms into the molten globule (B) form in a highly
      noncooperative transition populated by an ensemble of at least two intermediates.
      The B form is a dry molten globule in which water is excluded from the core, and
      in which secondary structure develops to 65% and tertiary contacts develop to
      40%, relative to that of the native protein. Kinetic refolding experiments
      carried out at pH 7 and at high Na(2)SO(4) concentrations, in which the rate of
      folding of the D form to the N state is compared to that of the B form to the N
      state, indicate conclusively that the B form is a productive intermediate that
      forms on the direct pathway of folding from the D form to the N state.

PMID- 11827515
TI  - Arg(362) and Tyr(365) of the botulinum neurotoxin type a light chain are involved
      in transition state stabilization.
AB  - The botulinum neurotoxin type A (BoNT/A) light chain (LC) acts as zinc
      endopeptidase. The X-ray structure of the toxin demonstrated that Zn(2+) is
      coordinated by His(222) and His(226) of the Zn(2+) binding motif HisGluXXHis and
      Glu(261), whereas Glu(223) coordinates the water molecule required for hydrolysis
      as the fourth ligand. Recent analysis of a cocrystal of the BoNT/B LC and its
      substrate synaptobrevin 2 suggested that Arg(362) and Tyr(365) of the homologous
      BoNT/A may be directly involved in catalysis. Their role and that of Glu(350)
      which is also found in the vicinity to the active site were analyzed by site
      directed mutagenesis. Various replacements of Arg(362) and substitution of
      Tyr(365) with Phe resulted in 79- and 34-fold lower k(cat)/K(m) values,
      respectively. These changes were provoked by decreased catalytic rates (k(cat))
      and not by alterations of ground state substrate binding as evidenced by largely
      unchanged K(d) and K(m) values. None of these mutations affected the overall
      secondary structure or zinc content of the LC. These findings suggest that the
      guanidino group of Arg(362) and the hydroxyl group of Tyr(365) together
      accomplish transition state stabilization as was proposed for thermolysin, being
      the prototypical member of the gluzincin superfamily of metalloproteases.
      Mutation of Glu(350) dramatically diminished the hydrolytic activity which must
      partly be attributed to an altered active site fine structure as demonstrated by
      an increased sensitivity toward heat-induced denaturing and a lower Zn(2+)
      binding affinity. Glu(350) apparently occupies a central position in the active
      site and presumably positions His(222) and Arg(362).

PMID- 11827516
TI  - Functional roles of conserved residues in the unstructured loop of Vibrio harveyi
      bacterial luciferase.
AB  - Residues 257-291 of the Vibrio harveyi bacterial luciferase alpha subunit
      comprise a highly conserved, protease-labile, disordered loop region, most of
      which is unresolved in the previously determined X-ray structures of the native
      enzyme. This loop region has been shown to display a time- dependent proteolysis
      resistance upon single catalytic turnover and was postulated to undergo
      conformational changes during catalysis ([AbouKhair, N. K., Ziegler, M. M., and
      Baldwin, T. O. (1985) Biochemistry 24, 3942-3947]. To investigate the role of
      this region in catalysis, we have performed site-specific mutations of different
      conserved loop residues. In comparison with V(max) and V(max)/K(m,flavin) of the
      native luciferase, the bioluminescence activities of alphaG284P were decreased to
      1-2% whereas those of alphaG275P and alphaF261D were reduced by 4-6 orders of
      magnitude. Stopped-flow results indicate that both alphaG275P and alphaF261D were
      able to form the 4a-hydroperoxy-FMN intermediate II but at lower yields. Both
      mutants also had enhanced rates for the intermediate II nonproductive dark decay
      and significantly compromised abilities to oxidize the decanal substrate.
      Additional mutations were introduced into the alphaG275 and alphaF261 positions,
      and the activities of the resulting mutants were characterized. Results indicate
      that the torsional flexibility of the alphaG275 residue and the bulky and
      hydrophobic nature of the alphaF261 residue were critical to the luciferase
      activity. Our results also support a functional role for the alpha subunit
      unstructured loop itself, possibly by serving as a mobile gating mechanism in
      shielding critical intermediates (including the excited flavin emitter) from
      exposure to medium.

PMID- 11827517
TI  - X-ray crystal structures of D100E trichodiene synthase and its pyrophosphate
      complex reveal the basis for terpene product diversity.
AB  - The 2.4 A resolution X-ray crystal structure of D100E trichodiene synthase and
      the 2.6 A resolution structure of its complex with inorganic pyrophosphate are
      reported. The D100E amino acid substitution in the so-called "aspartate-rich"
      motif does not result in large changes to the overall structure of the enzyme. In
      the pyrophosphate complex, however, pyrophosphate coordinates two Mg(2+) ions at
      the mouth of the active site without causing large changes in the structure of
      the enzyme. This contrasts with pyrophosphate binding in the wild-type enzyme,
      where pyrophosphate coordinates three Mg(2+) ions and triggers a significant
      conformational change that closes the mouth of the active site and optimizes
      packing density in the enzyme-substrate complex. The attenuation of active site
      closure in D100E trichodiene synthase compromises enzyme-substrate packing
      density and confers additional spatial and conformational degrees of freedom on
      the substrate and carbocation intermediates, which in turn results in the
      formation of five alternate sesquiterpene products in addition to trichodiene. By
      extension, then, the diversity of terpene cyclases in biology may have evolved in
      part by amino acid substitutions that fine-tune structural changes dependent on
      metal-diphosphate complexation that govern the formation of the active site
      template and enzyme-substrate packing density.

PMID- 11827518
TI  - Analysis of cholera toxin-ganglioside interactions by flow cytometry.
AB  - Cholera toxin entry into mammalian cells is mediated by binding of the pentameric
      B subunit (CTB) to ganglioside GM(1) in the cell membrane. We used flow cytometry
      to quantitatively measure in real time the interactions of fluorescently labeled
      pentameric cholera toxin B-subunit (FITC-CTB) with its ganglioside receptor on
      microsphere-supported phospholipid membranes. A model that describes the multiple
      steps of this mode of recognition was developed to guide our flow cytometric
      experiments and extract relevant equilibrium and kinetic rate constants. In
      contrast to previous studies, our approach takes into account receptor cross
      linking, an important feature for multivalent interactions. From equilibrium
      measurements, we determined an equilibrium binding constant for a single subunit
      of FITC-CTB binding monovalently to GM(1) presented in bilayers of approximately
      8 x 10(7) M(-1) while that for binding to soluble GM(1)-pentasaccharide was found
      to be approximately 4 x 10(6) M(-1). From kinetic measurements, we determined the
      rate constant for dissociation of a single site of FITC-CTB from microsphere
      supported bilayers to be (3.21 +/- 0.03) x 10(-3) s(-1), and the rate of
      association of a site on FITC-CTB in solution to a GM(1) in the bilayer to be
      (2.8 +/- 0.4) x 10(4) M(-1) s(-1). These values yield a lower estimate for the
      equilibrium binding constant of approximately 1 x 10(7) M(-1). We determined the
      equilibrium surface cross-linking constant [(1.1 +/- 0.1) x 10(-12) cm(2)] and
      from this value and the value for the rate constant for dissociation derived a
      value of approximately 3.5 x 10(-15) cm(2) s(-1) for the forward rate constant
      for cross-linking. We also compared the interaction of the receptor binding B
      subunit with that of the whole toxin (A- and B-subunits). Our results show that
      the whole toxin binds with approximately 100-fold higher avidity than the
      pentameric B-subunit alone which is most likely due to the additional interaction
      of the A(2)-subunit with the membrane surface. Interaction of cholera toxin B
      subunit and whole cholera toxin with gangliosides other than GM(1) revealed
      specific binding only to GD1(b) and asialo-GM(1). These interactions, however,
      are marked by low avidity and require high receptor concentrations to be
      observed.

PMID- 11827519
TI  - A Birch-like mechanism in enzymatic benzoyl-CoA reduction: a kinetic study of
      substrate analogues combined with an ab initio model.
AB  - Benzoyl-CoA reductase from the anaerobic bacterium Thauera aromatica catalyzes
      the ATP-driven two-electron reduction of the aromatic moiety of benzoyl-CoA. A
      Birch mechanism involving alternate one-electron and one-proton transfer steps to
      the aromatic ring was previously proposed for benzoyl-CoA reductase. Due to the
      high redox barrier, the first electron transfer step yielding a radical anion is
      considered the rate-limiting step in this reaction. Focusing on the mechanism of
      substrate reduction, this work combines the kinetic analysis of a number of
      substrate analogues with a model based on the ab initio calculated electron
      density of the radical anion of benzoyl-CoA, a transition state model of the
      proposed Birch mechanism. Both K(m) and k(cat) of ortho-substituted benzoyl-CoA
      increased in parallel with the substituent's acceptor strength (F > Cl = H > OH >
      NH(2)). Among the isomers of monofluorobenzoyl-CoA, reduction rates decreased in
      the following order: ortho > meta > para; the K(m) values increased in the
      following order: meta > ortho > para. Five-ring heteroaromatic acid thiol esters
      were reduced in the following order: thiophene > furan > pyrrole; the 2-isomers
      are reduced much faster than the 3-isomers. Most of these results could be
      rationalized by the model. A Hammett plot indicated that the reaction mechanism
      is only slightly polar, suggesting the involvement of a partial protonation of
      the carbonyl oxygen of benzoyl-CoA and/or a simultaneous transfer of the first
      electron and proton. Surprisingly, benzoyl-CoA reductase exhibited a hydrogen
      kinetic isotope effect on k(cat) for pyridine-2-carbonyl-CoA (2.1) but only a
      negligible one for benzoyl-CoA (1.2), indicating that pyridine-2-carbonyl-CoA
      reduction proceeds according to a varied mechanism.

PMID- 11827520
TI  - Characterization of the tertiary structure of soluble CD4 bound to glycosylated
      full-length HIVgp120 by chemical modification of arginine residues and mass
      spectrometric analysis.
AB  - The initial step of infection of blood cells with the human immunodeficiency
      virus, HIV, is the formation of a complex of the viral envelope protein gp120 and
      its human receptor CD4. We have examined structural features of recombinant
      soluble CD4 (sCD4) by chemical modification of arginine residues with
      hydroxyphenylglyoxal and subsequent analysis by matrix-assisted laser
      desorption/ionization and electrospray ionization mass spectrometry. As R58, R59,
      R131, R134, R219, R240, R293, and R329 could be derivatized free in solution,
      these arginine residues were exposed on the surface of the protein. In the
      noncovalent complex of sCD4 with HIV(SF2)gp120, only R58, R131, R134, R219, R240,
      R293, and R329 were accessible for the derivatizing agent. R59 was shielded from
      hydroxyphenylglyoxal and was, therefore, considered to be part of the interaction
      site with gp120. This indicates that the carbohydrate moieties and the flexible
      variable loops of the glycosylated full-length gp120 from HIV strain SF2 do not
      induce a reorganization of CD4 in its binding to gp120 and, therefore, do not
      appear to significantly affect the structural orientation of the primary receptor
      in complex with the HIV envelope protein as compared to the binding observed in
      the crystal structure of CD4 with truncated deglycosylated gp120.

PMID- 11827521
TI  - Structural studies of the interaction between ubiquitin family proteins and
      proteasome subunit S5a.
AB  - The 26S proteasome is essential for the proteolysis of proteins that have been
      covalently modified by the attachment of polyubiquitinated chains. Although the
      20S core particle performs the degradation, the 19S regulatory cap complex is
      responsible for recognition of polyubiquitinated substrates. We have focused on
      how the S5a component of the 19S complex interacts with different ubiquitin-like
      (ubl) modules, to advance our understanding of how polyubiquitinated proteins are
      targeted to the proteasome. To achieve this, we have determined the solution
      structure of the ubl domain of hPLIC-2 and obtained a structural model of hHR23a
      by using NMR spectroscopy and homology modeling. We have also compared the S5a
      binding properties of ubiquitin, SUMO-1, and the ubl domains of hPLIC-2 and
      hHR23a and have identified the residues on their respective S5a contact surfaces.
      We provide evidence that the S5a-binding surface on the ubl domain of hPLIC-2 is
      required for its interaction with the proteasome. This study provides structural
      insights into protein recognition by the proteasome, and illustrates how the
      protein surface of a commonly utilized fold has highly evolved for various
      biological roles.

PMID- 11827522
TI  - 8-(Hydroxymethyl)-3,N(4)-etheno-C, a potential carcinogenic glycidaldehyde
      product, miscodes in vitro using mammalian DNA polymerases.
AB  - 8-(Hydroxymethyl)-3,N(4)-etheno-C (8-HM-epsilonC) is an exocyclic adduct
      resulting from the reaction of dC with glycidaldehyde, a mutagen and animal
      carcinogen. This compound has now been synthesized and its phosphoramidite
      incorporated site-specifically into a defined 25-mer oligonucleotide. In this
      study, the mutagenic potential of this adduct in the 25-mer oligonucleotide was
      investigated in an in vitro primer-template extension assay using four mammalian
      DNA polymerases. The miscoding potentials were also compared to those of an
      analogous derivative, 3,N(4)-etheno C (epsilonC), in the same sequence. Both
      adducts primarily blocked replication by calf thymus DNA polymerase alpha at the
      modified base, while human polymerase beta catalyzed measurable replication
      synthesis through both adducts. Nucleotide insertion experiments showed that dA
      and dC were incorporated by pol beta opposite either adduct, which would result
      in a C --> T transition or C --> G transversion. Human polymerase eta, a product
      of the xeroderma pigmentosum variant (XP-V) gene, catalyzed the most efficient
      bypass of the two lesions with 25% and 32% for 8-HM-epsilonC and epsilonC
      bypassed after 15 min. Varying amounts of all four bases opposite the modified
      bases resulted with pol eta. Human polymerase kappa primarily blocked synthesis
      at the base prior to the adduct. However, some specific misincorporation of dT
      resulted, forming an epsilonC.T or 8-HM-epsilonC.T pair. From these data, we
      conclude that the newly synthesized glycidaldehyde-derived adduct, 8-HM-epsilonC,
      is a miscoding lesion. The bypass efficiency and insertion specificity of 8-HM
      epsilonC and epsilonC were similar for all four polymerases tested, which could
      be attributed to the similar planarity and sugar conformations for these two
      derivatives as demonstrated by molecular modeling studies.

PMID- 11827523
TI  - Dynamic docking of myosin and actin observed with resonance energy transfer.
AB  - Atomic models of myosin subfragment-1 (S1) and the actin filament are docked
      together using resonance energy-transfer data from both pre- and postpowerstroke
      conditions. The quality of the resulting best fits discriminated between neck
      region orientations of the S1 for a given set of experimental conditions. For
      measurements of the postpowerstroke states in the presence of ADP, resonance
      energy-transfer data alone are sufficient to dock the atomic models and provide
      evidence that S1 exists with at least two neck-region orientations under these
      conditions. To dock the prepowerstroke state, resonance energy-transfer data were
      used in combination with previous chemical cross-linking data to determine that a
      neck-region orientation similar to that of a proposed prepowerstroke state best
      fit the data. The resulting models determined independently from electron
      microscopy compare favorably with micrographs from the recent literature. The
      docking models by resonance energy transfer suggest that the larger movements in
      the light-chain binding domain are accompanied by twisting and rotating movements
      of the catalytic domain, causing a tilt of approximately 30 degrees during the
      weak-to-strong transition. This transition provides the displacement necessary to
      support motility and force generation.

PMID- 11827524
TI  - Structural definition of the active site and catalytic mechanism of 3,4-dihydroxy
      2-butanone-4-phosphate synthase.
AB  - X-ray crystal structures of L-3,4-dihydroxy-2-butanone-4-phosphate synthase from
      Magnaporthe grisea are reported for the E-SO(4)(2-), E-SO(4)(2-)-Mg(2+), E
      SO(4)(2)(-)-Mn(2+), E-SO(4)(2)(-)-Mn(2+)-glycerol, and E-SO(4)(2)(-)-Zn(2+)
      complexes with resolutions that extend to 1.55, 0.98, 1.60, 1.16, and 1.00 A,
      respectively. Active-site residues of the homodimer are fully defined. The
      structures were used to model the substrate ribulose 5-phosphate in the active
      site with the phosphate group anchored at the sulfate site and the placement of
      the ribulose group guided by the glycerol site. The model includes two Mg(2+)
      cations that bind to the oxygen substituents of the C2, C3, C4, and phosphate
      groups of the substrate, the side chains of Glu37 and His153, and water
      molecules. The position of the metal cofactors and the substrate's phosphate
      group are further stabilized by an extensive hydrogen-bond and salt-bridge
      network. On the basis of their proximity to the substrate's reaction
      participants, the imidazole of an Asp99-His136 dyad from one subunit, the side
      chains of the Asp41, Cys66, and Glu174 residues from the other subunit, and
      Mg(2+)-activated water molecules are proposed to serve specific roles in the
      catalytic cycle as general acid-base functionalities. The model suggests that
      during the 1,2-shift step of the reaction, the substrate's C3 and C4 hydroxyl
      groups are cis to each other. A cis transition state is calculated to have an
      activation barrier that is 2 kcal/mol greater than that of the trans transition
      state in the absence of the enzyme.

PMID- 11827525
TI  - Rapid kinetic studies of acetyl-CoA synthesis: evidence supporting the catalytic
      intermediacy of a paramagnetic NiFeC species in the autotrophic Wood-Ljungdahl
      pathway.
AB  - CO dehydrogenase/acetyl-CoA synthase (CODH/ACS), a key enzyme in the Wood
      Ljungdahl pathway of anaerobic CO(2) fixation, is a bifunctional enzyme
      containing CODH, which catalyzes the reversible two-electron oxidation of CO to
      CO(2), and ACS, which catalyzes acetyl-CoA synthesis from CoA, CO, and a
      methylated corrinoid iron-sulfur protein (CFeSP). ACS contains an active site
      nickel iron-sulfur cluster that forms a paramagnetic adduct with CO, called the
      nickel iron carbon (NiFeC) species, which we have hypothesized to be a key
      intermediate in acetyl-CoA synthesis. This hypothesis has been controversial.
      Here we report the results of steady-state kinetic experiments; stopped-flow and
      rapid freeze-quench transient kinetic studies; and kinetic simulations that
      directly test this hypothesis. Our results show that formation of the NiFeC
      intermediate occurs at approximately the same rate as, and its decay occurs 6
      fold faster than, the rate of acetyl-CoA synthesis. Kinetic simulations of the
      steady-state and transient kinetic results accommodate the NiFeC species in the
      mechanism and define the rate constants for the elementary steps in acetyl-CoA
      synthesis. The combined results strongly support the kinetic competence of the
      NiFeC species in the Wood-Ljungdahl pathway. The results also imply that the
      methylation of ACS occurs by attack of the Ni(1+) site in the NiFeC intermediate
      on the methyl group of the methylated CFeSP. Our results indicate that CO
      inhibits acetyl-CoA synthesis by inhibiting this methyl transfer reaction. Under
      noninhibitory CO concentrations (below 100 microM), formation of the NiFeC
      species is rate-limiting, while at higher inhibitory CO concentrations, methyl
      transfer to ACS becomes rate-limiting.

PMID- 11827526
TI  - Hydroxylation of specifically deuterated limonene enantiomers by cytochrome p450
      limonene-6-hydroxylase reveals the mechanism of multiple product formation.
AB  - The regiochemistry and facial stereochemistry of the limonene-6-hydroxylase-
      (CYP71D18-) mediated hydroxylation of the monoterpene olefin limonene are
      determined by the absolute configuration of the substrate. (-)-(4S)-Limonene is
      hydroxylated at the C6 allylic position to give (-)-trans-carveol as the only
      product, whereas (+)-(4R)-limonene yields multiple hydroxylation products with
      (+)-cis-carveol predominating. Specifically deuterated limonene enantiomers were
      prepared to investigate the net stereospecificity of hydroxylation at C6 and the
      mechanism of multiple product formation. The results of isotopically sensitive
      branching experiments of competitive and noncompetitive design were consistent
      with a nondissociative kinetic mechanism, indicating that (4R)-limonene has
      sufficient freedom of motion within the active site of CYP71D18 to allow
      formation of either the trans-3- or cis-6-hydroxylated product. However, the
      kinetic isotope effects resulting from deuterium abstraction were significantly
      smaller than expected for an allylic hydroxylation, and they did not approach the
      intrinsic isotope effect. (4S)-Limonene is oxygenated with almost complete
      stereospecificity for hydrogen abstraction from the trans-6-position,
      demonstrating rigid orientation during hydrogen abstraction and hydroxyl
      delivery. The oxygenation of (4R)-limonene leading to the formation of (+/-)
      trans-carveol is accompanied by considerable allylic rearrangement and
      stereochemical scrambling, whereas the formation of (+)-cis-carveol proceeds
      without allylic rearrangement and with nearly complete stereospecificity for
      hydrogen abstraction from the cis-6-position. These results demonstrate that a
      single cytochrome P450 enzyme catalyzes the hydroxylation of small antipodal
      substrates with distinct stereochemistries and reveal that substrate-dependent
      positional motion of the intermediate carbon radical (and, therefore,
      hydroxylation stereospecificity) is determined by active-site binding
      complementarity. Thus, epimerization and allylic rearrangement are not inherent
      features of these reactions but occur when loss of active-site complementarity
      allows increased substrate mobility.

PMID- 11827527
TI  - Yeast cystathionine beta-synthase reacts with L-allothreonine, a non-natural
      substrate, and L-homocysteine to form a new amino acid, 3-methyl-L-cystathionine.
AB  - Our studies of the reaction mechanism of cystathionine beta-synthase from yeast
      (Saccharomyces cerevisiae) are facilitated by the spectroscopic properties of the
      pyridoxal phosphate coenzyme. The enzyme catalyzes the reaction of L-serine with
      L-homocysteine to form L-cystathionine through a series of pyridoxal phosphate
      intermediates. In this work, we explore the substrate specificity of the enzyme
      by use of substrate analogues combined with kinetic measurements under pre-steady
      state conditions and with circular dichroism and fluorescence spectroscopy under
      steady-state conditions. Our results show that L-allothreonine, but not L
      threonine, serves as an effective substrate. L-Allothreonine reacts with the
      pyridoxal phosphate cofactor to form a stable 3-methyl aminoacrylate intermediate
      that absorbs maximally at 446 nm. The rapid-scanning stopped-flow results show
      that the binding of L-allothreonine as the external aldimine is faster than
      formation of the 3-methyl aminoacrylate intermediate. The 3-methyl aminoacrylate
      intermediate reacts with L-homocysteine to form a new amino acid, 3-methyl-L
      cystathionine, which was characterized by nuclear magnetic resonance
      spectroscopy. This new amino acid may be a useful analogue of L-cystathionine.

PMID- 11827528
TI  - Abietadiene synthase catalysis: conserved residues involved in protonation
      initiated cyclization of geranylgeranyl diphosphate to (+)-copalyl diphosphate.
AB  - Abietadiene synthase catalyzes two sequential, mechanistically distinct
      cyclization reactions in the formation of a mixture of abietadiene double bond
      isomers as the committed step in resin acid biosynthesis. Each reaction is
      carried out at a separate active site residing in a structurally distinct domain,
      and the reactions are kinetically separable. The first cyclization reaction is
      initiated by protonation of the terminal double bond of the universal diterpene
      precursor, geranylgeranyl diphosphate. The pH dependence of the overall reaction
      is consistent with an acid-base catalytic mechanism, and a divalent metal ion
      plays a role in this reaction probably by binding the diphosphate moiety to
      assist in positioning the substrate for catalysis. A putative active site for the
      protonation-initiated cyclization was defined by modeling abietadiene synthase
      and locating the DXDD motif previously shown to be involved in this reaction. A
      number of charged and aromatic residues, which are highly conserved in
      mechanistically related diterpene cyclases, line the putative active site.
      Alanine substitutions were made for each of these residues, as were asparagine
      and glutamate substitutions for the aspartates of the DXDD motif. Kinetic
      evaluation confirmed the involvement of most of the targeted residues in the
      reaction, and analysis of mutational effects on the pH-activity profile and
      affinity for a transition state analogue suggested specific roles for several of
      these residues in catalyzing the cyclization of geranylgeranyl diphosphate to (+)
      copalyl diphosphate. A functional role was also suggested for the cryptic
      insertional element found in abietadiene synthase and other diterpene synthases
      that carry out similar protonation-initiated cyclizations.

PMID- 11827529
TI  - A revised mechanism for the inactivation of bovine liver enoyl-CoA hydratase by
      (methylenecyclopropyl)formyl-CoA based on unexpected results with the C114A
      mutant.
AB  - The compound (methylenecyclopropyl)formyl-CoA (MCPF-CoA) has been reported
      earlier as a potent active site-directed inactivator of bovine liver enoyl-CoA
      hydratase (ECH). It is believed that the mechanism of inactivation involves the
      attack of Cys114 at C-2' of MCPF-CoA, resulting in ring cleavage and permanent
      covalent modification of the enzyme. Here, we describe studies with the C114A
      mutant of bovine liver ECH, which was constructed and purified to determine the
      role of this residue in the catalytic mechanism of the enzyme. The C114A mutant,
      which is catalytically competent, shows an unexpected susceptibility to
      inactivation by MCPF-CoA, indicating that Cys114 is not the primary nucleophile
      responsible for the inactivation of the enzyme. To determine if catalytic
      residues Glu115 and Glu135 play a role in the inactivation of the enzyme, the
      E115Q and E135Q mutants were also constructed and purified. It was determined
      that these mutants did not react with MCPF-CoA, indicating a possible role for
      both residues in the inactivation of the wild-type enzyme. Pepsin digestion and
      subsequent LC-MS/MS analysis of the inactivated wild-type enzyme and C114A mutant
      revealed that Glu115 was modified in each case, supporting the hypothesis that
      this residue is the true nucleophile that traps MCPF-CoA and indicating that the
      covalent modification of Cys114 reported earlier may be a postinactivation
      artifact. We propose a modified mechanism of inactivation involving Glu115 and
      Glu135, and suggest that MCPF-CoA may be a mechanism-based inhibitor for bovine
      liver ECH.

PMID- 11827530
TI  - Exploring the role and the binding affinity of a second zinc equivalent in B.
      cereus metallo-beta-lactamase.
AB  - Metallo-beta-lactamases are a newly characterized family of zinc enzymes present
      in several pathogenic strains that represent an emerging clinical threat. Enzymes
      from different organisms exhibit an outstanding functional diversity,
      particularly in the metal ion requirements for activity. We have investigated the
      effect of the second zinc(II) equivalent in the enzyme betaLII from Bacillus
      cereus, naturally active in the mono-zinc(II) form. The enzyme is reversibly
      inactivated at low pH, due to dissociation of the two zinc(II) equivalents. The
      pH profile indicates that zinc-bound water in the mono-zinc(II) enzyme possesses
      a pK(a) below 4.9, indicating that a second zinc(II) equivalent is not needed for
      nucleophile activation. Instead, the second zinc(II) may contribute to properly
      anchor Asp120, that ultimately orients the attacking nucleophile in binuclear
      enzymes. This role may be fulfilled by Arg121 in mono-zinc enzymes, as suggested
      by the kinetic study of the R121C mutant in betaLII. In addition, it is
      demonstrated that Arg121 is not responsible for the low binding affinity of
      betaLII toward a second zinc(II) equivalent.

PMID- 11827531
TI  - Identification of glutamic acid 479 as the gluzincin coordinator of zinc in FtsH
      (HflB).
AB  - Escherichia coli FtsH (HflB) is a membrane-bound and ATP-dependent
      metalloprotease. Its cytoplasmic domain contains a zinc-binding motif,
      H(417)EXXH, whose histidine residues have been shown to be functionally
      important. Although they are believed to be involved directly in zinc
      coordination, nothing is known about the third zinc ligand of this protease.
      Sequence alignment indicates that glutamic acid residues are conserved among the
      FtsH homologues at positions corresponding to Glu(479) and Glu(585) of E. coli
      FtsH. We replaced each of them by Gln, Asp, Lys, or Val. Mutations at position
      479 compromised the proteolytic functions of FtsH in vivo. In vitro proteolytic
      activities of the E479Q, E479V, and E479D mutant enzymes were much lower than
      that of the wild-type protein and were significantly stimulated by a high
      concentration of zinc ion. These mutant proteins retained the wild-type levels of
      ATPase activities, and their trypsin susceptibilities as well as CD spectra were
      essentially indistinguishable from those of the wild-type protein, indicating
      that the mutations did not cause gross conformational changes in FtsH. They
      exhibited reduced zinc contents upon purification. From these results, we
      conclude that Glu(479) is a zinc-coordinating residue.

PMID- 11827532
TI  - Conformational heterogeneity is revealed in the dissociation of the oligomeric
      chaperonin GroEL by high hydrostatic pressure.
AB  - We investigated the dissociation of tetradecameric GroEL by high hydrostatic
      pressure in the range of 1-2.5 kbar. Kinetics of the dissociation of GroEL in the
      absence and presence of Mg(2+) and/or KCl were monitored using light scattering.
      All of the kinetics were biphasic in nature. At any given pressure, only monomers
      and 14mers were produced, and below 2.5 kbar, the 14mers only partially
      dissociated to monomers, which did not significantly reassemble on
      depressurization. Under identical reaction conditions, the observed dissociation
      rates decreased by only 2-fold when the concentration of GroEL was increased by
      20-fold. At 2.5 kbar the observed rates decreased exponentially with the increase
      in [KCl] and reached a minimum at approximately 75mM. Similarly, the rates
      decreased with the increase in [Mg(2+)] and reached a minimum at approximately 3
      mM Mg(2+). In the presence of saturating amounts of Mg(2+) (10 mM) and KCl (100
      mM), the rates were much faster than with 10 mM Mg(2+) alone. The results could
      be rationalized in terms of the presence of GroEL heterogeneity, which could not
      be assessed easily by common techniques such as sedimentation velocity, HPLC, gel
      electrophoresis, and dissociation by chaotropes. This heterogeneity is evidence
      of subpopulations of GroEL that dissociate at different pressures. At low
      pressures, the oligomer without added Mg(2+) only partially dissociates to
      monomers, leading to an apparent plateau in the kinetics, whereas in the presence
      of Mg(2+) the species are converted to a tighter Mg(2+)-bound species, leading to
      a much slower dissociation process. The presence of KCl in the sample also leads
      to similar heterogeneity.

PMID- 11827533
TI  - Crystal structures of the Bacillus licheniformis BS3 class A beta-lactamase and
      of the acyl-enzyme adduct formed with cefoxitin.
AB  - The Bacillus licheniformis BS3 beta-lactamase catalyzes the hydrolysis of the
      beta-lactam ring of penicillins, cephalosporins, and related compounds. The
      production of beta-lactamases is the most common and thoroughly studied cause of
      antibiotic resistance. Although they escape the hydrolytic activity of the
      prototypical Staphylococcus aureus beta-lactamase, many cephems are good
      substrates for a large number of beta-lactamases. However, the introduction of a
      7alpha-methoxy substituent, as in cefoxitin, extends their antibacterial spectrum
      to many cephalosporin-resistant Gram-negative bacteria. The 7alpha-methoxy group
      selectively reduces the hydrolytic action of many beta-lactamases without having
      a significant effect on the affinity for the target enzymes, the membrane
      penicillin-binding proteins. We report here the crystallographic structures of
      the BS3 enzyme and its acyl-enzyme adduct with cefoxitin at 1.7 A resolution. The
      comparison of the two structures reveals a covalent acyl-enzyme adduct with
      perturbed active site geometry, involving a different conformation of the omega
      loop that bears the essential catalytic Glu166 residue. This deformation is
      induced by the cefoxitin side chain whose position is constrained by the presence
      of the alpha-methoxy group. The hydrolytic water molecule is also removed from
      the active site by the 7beta-carbonyl of the acyl intermediate. In light of the
      interactions and steric hindrances in the active site of the structure of the BS3
      cefoxitin acyl-enzyme adduct, the crucial role of the conserved Asn132 residue is
      confirmed and a better understanding of the kinetic results emerges.

PMID- 11827534
TI  - Enzymatic reaction of hydrogen peroxide-dependent peroxygenase cytochrome P450s:
      kinetic deuterium isotope effects and analyses by resonance Raman spectroscopy.
AB  - Cytochromes P450SP(alpha) (CYP152B1) and P450BS(beta) (CYP152A1), which are
      isolated from Sphingomonas paucimobilis and Bacillus subtilis, respectively,
      belong to the P450 superfamily, but catalyze hydroxylation reactions, in which an
      oxygen atom from H2O2 is efficiently introduced into fatty acids (e.g., myristic
      acid). P450SP(alpha) produces the alpha-hydroxylated (alpha-OH) products at 100%,
      while P450BS(beta) produces alpha- and beta-hydroxylated (beta-OH) products at 33
      and 67%, respectively. Using deuterium-substituted fatty acids ([2,2-d2]-myristic
      acid and d27-myristic acid) as a substrate, the peroxygenase reactions of the two
      bacterial P450s were investigated. In the P450SP(alpha) reaction, we observed an
      intermolecular noncompetitive kinetic isotope effect on Vmax (DV = 4.1) when [2,2
      d2]-myristic acid was used, suggesting that an isotopically sensitive step
      involving the alpha-hydrogen of the fatty acid is present in the catalytic cycle.
      On the other hand, D(V/K) was masked, in sharp contrast to the features of usual
      monooxygenases P450. The characteristic kinetic features can be interpreted in
      terms of the faster product formation than the substrate dissociation. A similar
      kinetic isotope effect was observed [DV = 4.9, D(V/K) approximately 1] for the
      P450BS(beta) reaction, when d27-myristic acid was used as a substrate, indicating
      that the reaction mechanism is the same for both peroxygenases. The resonance
      Raman spectral data of P450BS(beta) in the ferric and ferrous-CO forms in the
      presence and absence of myristic acid demonstrated that the catalytic pocket of
      the enzyme is polar, so that the location of the carboxylate of the substrate
      close to the sixth ligand of the heme could be allowed. On the basis of these
      results on the kinetic isotope effects and spectroscopy, we discuss the possible
      mechanisms of the alpha- and beta-hydroxylation of fatty acids catalyzed by
      peroxygenases P450SP(alpha) and P450BS(beta).

PMID- 11827535
TI  - Comparison between UV Raman and circular dichroism detection of short alpha
      helices in bombolitin III.
AB  - We have used UV resonance Raman (UVRR) and circular dichroism (CD) spectroscopies
      to examine the dilute solution-phase secondary structure of the 17 amino acid
      peptide Bombolitin III (BIII). Both UVRR and CD clearly observe the alpha-helix
      structure induced by the addition of trifluoroethanol (TFE) to BIII. In contrast,
      only UVRR is able to detect the single alpha-helical turn induced by increasing
      the pH of BIII from pH 1.8 to 6.4. This alpha-helical turn is formed because of a
      stabilizing salt bridge formed between Lys(2) and Asp(5). Further increases in
      the alpha-helix content occur as the pH is raised further. We compare the
      relative sensitivity of UVRR and CD to short alpha helices and find, as expected,
      that the CD cannot detect short alpha helices. This study demonstrates that UV
      Raman measurements can detect the formation of single alpha-helical turns which
      cannot be detected by CD measurements.

PMID- 11827536
TI  - Effect of phosphorylation on alpha-helix stability as a function of position.
AB  - We have investigated the effect of placing phosphoserine at the N-cap, N1, N2,
      N3, and interior position in alanine-based alpha-helical peptides. Helix contents
      of each peptide were measured by CD spectroscopy and titrations performed to
      determine pK(a) values. Data were analyzed with modified Lifson-Roig theory to
      determine helix-coil parameters (n, n(1), n(2), n(3), and w) and free energy
      changes for phosphoserine at each helical position. Results are given for a -1
      and -2 phosphoserine charge state. Results show that phosphoserine stabilizes at
      the N-terminal positions by as much as 2.3 kcal.mol(-1), while destabilizes in
      the helix interior by 1.2 kcal.mol(-1), relative to serine. The rank order of
      free energies relative to serine at each position is N2 > N3 > N1 > N-cap >
      interior. Moreover, -2 phosphoserine is the most preferred residue known at each
      of these N-terminal positions. Experimental pK(a) values for the -1 to -2
      phosphoserine transition are in the order N2 < N-cap < N1 < N3 < interior. This
      order agrees well with electrostatics calculations carried out with phosphoserine
      at the N-terminal positions and interior positions. Combining these with
      calculations at the C3, C2, C1, and C-cap positions gives results for
      phosphoserine along the length of the helix. We see a transition from
      phosphoserine stabilization at the N-terminus to destabilization at the C
      terminus and can explain this in terms of the balance of protein solvation,
      favorable interactions, and dehydration. These results give insight into the
      phosphorylatable control of biological systems through positive or negative
      changes in stability.

PMID- 11827537
TI  - Characterization of transient protein folding intermediates during myoglobin
      reconstitution by time-resolved electrospray mass spectrometry with on-line
      isotopic pulse labeling.
AB  - A novel technique for studying protein folding kinetics is presented. It is based
      on a continuous-flow setup that is coupled to an electrospray (ESI) mass
      spectrometer and allows initiation of a folding reaction, followed by isotopic
      pulse labeling. The protein is electrosprayed "quasi-instantaneously" after
      exposure to the deuterated solvent. This approach yields structural information
      from the ESI charge state distribution and from the H/D exchange levels of
      individual protein states, while at the same time noncovalent interactions can be
      monitored. This technique is used to study the reconstitution of holomyoglobin
      (hMb) from unfolded apomyoglobin (aMb) and free heme. MS/MS is used to establish
      that a short-lived folding intermediate with two heme groups attached represents
      a protein-bound heme dimer. This state appears to have a compactness close to
      that of native hMb; however, isotopic labeling indicates a significantly
      perturbed structure. Another intermediate is bound to a single heme group and
      shows a charge state distribution similar to that of unfolded aMb. Exchange
      levels exhibited by this state are lower than for unfolded aMb, indicating that
      fewer hydrogens are exposed to the solvent and/or that more of them are involved
      in hydrogen bonding. Native hMb leads to the formation of low charge state ions
      (hMb(9+), hMb(8+)) and shows low exchange levels. However, early during
      reconstitution, a slightly unfolded form of the heme-protein complex contributes
      to the observed hMb(9+) ions. A peak width analysis reveals that the structural
      heterogeneity of some of the observed protein species decreases as reconstitution
      proceeds.

PMID- 11827538
TI  - Light-induced unfolding of photoactive yellow protein mutant M100L.
AB  - Light-activation of the PAS domain protein photoactive yellow protein (PYP) is
      believed to trigger a negative phototactic response in the phototropic bacterium
      Halorhodospira halophila. To investigate transient conformational changes of the
      PYP photocycle, we utilized the PYP mutant M100L that displays an increased
      lifetime of the putative signaling-state photointermediate PYP(M) by 3 orders of
      magnitude, as previously reported for the M100A mutant [Devanathan, S., Genick,
      U. K., Canestrelli, I. L., Meyer, T. E., Cusanovich, M. A., Getzoff, E. D., and
      Tollin, G. Biochemistry (1998) 37, 11563-11568]. The FTIR difference spectrum of
      PYP(M) and the ground state of M100L demonstrated extensive peptide-backbone
      structural changes as observed in the FTIR difference spectrum of the wild-type
      protein and PYP(M). The conformational change investigated by CD spectroscopy in
      the far-UV region showed reduction of the alpha-helical content by approximately
      40%, indicating a considerable amount of changes in the secondary structure. The
      optical activity of the p-coumaric acid chromophore completely vanished upon
      PYP(M) in contrast to the dark state, indicating deformation of the binding
      pocket structure in PYP(M). The tertiary structural changes were further
      monitored by small-angle X-ray scattering measurements, which demonstrated a
      significant increase of the radius of gyration of the molecule by approximately
      5% in PYP(M). These structural changes were reversed concomitantly with the
      chromophore anionization upon the dark state recovery. The observed changes of
      the quantities provided a more vivid view of the structural changes of the mutant
      PYP in going from PYP(M) to PYP(dark), which can be regarded as a process of
      folding of the secondary and the tertiary structures of the "PAS" domain
      structure, coupled with the p-coumaric acid chromophore deprotonation and
      isomerization.

PMID- 11827539
TI  - Hints of nonhierarchical folding of acidic fibroblast growth factor.
AB  - We have analyzed by circular dichroism (CD) and proton nuclear magnetic resonance
      (NMR) the helical propensity of the all-beta protein acidic fibroblast growth
      factor (aFGF) and two peptides corresponding to beta-strand 8 (beta8 peptide,
      amino acids 95-107) and the beta-strand 8/turn/beta-strand 9 hairpin (beta8/9
      peptide, amino acids 95-114), which has been involved in receptor binding. A
      secondary structure prediction of aFGF carried out by several procedures labels
      the 95-104 sequence as predominantly alpha-helical. A titration of aFGF with
      2,2,2-trifluoroethanol (TFE) induces a change in the far-UV CD spectrum of the
      protein giving rise to a prominent alpha-helical shape (22% alpha-helix). The
      cooperativity of the transition and the moderate TFE concentrations used
      (midpoint at 24%) suggest that the effect of TFE is specific. Moreover, a
      titration performed at pH 2 yields a higher amount of alpha-helix (55%) at a
      smaller TFE concentration. Synthetic peptides containing the beta8 and beta8/9
      sequences display a random coil conformation at pH 7 but acquire alpha-helical
      structure in the presence of TFE, methanol, and SDS micelles. At pH below 3.0 a
      significant amount (20-30%) of alpha-helical conformation is present in both the
      beta8 and beta8/9 peptides even in the absence of other solvent additives. The
      secondary structure of the peptides was determined by proton nuclear magnetic
      resonance (1H NMR). These results suggest that the 95-114 sequence of aFGF has
      helical propensity and that the protein may fold nonhierarchically in the early
      steps of folding, acquiring its final beta-structure by a later interaction with
      the rest of the polypeptide.

PMID- 11827540
TI  - Structural and guanosine triphosphate/diphosphate requirements for transit
      peptide recognition by the cytosolic domain of the chloroplast outer envelope
      receptor, Toc34.
AB  - Toc34 is a transmembrane protein located in the outer envelope membrane of
      chloroplasts and involved in transit peptide recognition. The cytosolic region of
      Toc34 reveals 34% alpha-helical and 26% beta-strand structure and is stabilized
      by intramolecular electrostatic interaction. Toc34 binds both chloroplast
      preproteins and isolated transit peptides in a guanosine triphosphate- (GTP-)
      dependent mechanism. In this study we demonstrate that the soluble, cytosolic
      domain of Toc34 (Toc34deltaTM) functions as receptor in vitro and is capable to
      compete with the import of the preprotein of the small subunit (preSSU) of
      ribulose-1,5-bisphosphate carboxylase-oxygenase into chloroplasts in a GTP
      dependent manner. We have developed a biosensor assay to study the interaction of
      Toc34deltaTM with purified preproteins and transit peptides. The results are
      compared with the interactions of both a full-size preprotein and the transit
      peptide of preSSU with the translocon of the outer envelope of chloroplasts (Toc
      complex) in situ. Several mutants of the transit peptide of preSSU were evaluated
      to identify amino acid segments that are specifically recognized by Toc34. We
      present a model of how Toc34 may recognize the transit peptide and discuss how
      this interaction may facilitate interaction and translocation of preproteins via
      the Toc complex in vivo.

PMID- 11827541
TI  - Transmembrane domains confer different substrate specificities and adenosine
      diphosphate hydrolysis mechanisms on CD39, CD39L1, and chimeras.
AB  - Members of the ecto-nucleoside triphosphate diphosphohydrolase (eNTPDase) family
      exhibit distinctive substrate specificities, but how such specificities are
      achieved by enzymes with identical putative catalytic domains is unknown.
      Previously we showed that H59G substitution changes CD39 from an apyrase to an
      adenosine diphosphatase (ADPase) in a manner that depends on intact associations
      of both transmembrane domains with the membrane. Here we show that the
      extracellular domain of CD39L1 ecto-adenosine triphosphatase (ecto-ATPase) has
      the same 3:1 ATP:ADP hydrolysis ratio as the extracellular domain of CD39,
      suggesting that the transmembrane domains are required to confer the native
      substrate specificities on each enzyme. As in CD39, H50G substitution has little
      effect on the activity of the CD39L1 extracellular domain or solubilized
      monomers. However, H50G substitution diminishes both ATPase and ADPase activities
      of native CD39L1, in contrast to its selective effect on ATPase activity in CD39,
      suggesting that the transmembrane domains confer different ADP hydrolysis
      mechanisms on CD39 and CD39L1. We then show that the transmembrane domains of
      CD39L1 can substitute for those of CD39 in conferring native CD39 substrate
      specificity and regulation of H59 but that the transmembrane domains of CD39
      confer neither CD39 nor CD39L1 properties on the CD39L1 extracellular domain.
      These results suggest that non-apyrase conserved region residues in the
      extracellular domain contain the information specifying CD39 native properties
      but have a nonspecific requirement for two transmembrane domains to manifest the
      information.

PMID- 11827542
TI  - Rotational dynamics of the epidermal growth factor receptor.
AB  - We have examined the rotational mobility of SL-EGF, a bifunctional adduct of
      bis(sulfo-N-succinimidyl)-[(15)N,(2)H(16)]-doxyl-2-spiro-4'-pimelate and
      [Lys3,Tyr22]-murine epidermal growth factor, bound to the EGF receptor in A431
      membrane vesicles. The linear EPR spectrum indicated that there was essentially
      no free SL-EGF in the bound complex preparation. To better define the rotational
      mobility of the SL-EGF bound to the EGF receptor, ST-EPR spectra were obtained at
      multiple Zeeman field modulation frequencies. Global analysis with a uniaxial
      rotational diffusion model of the ST-EPR data yielded two minima that have
      differences in rotational mobility and in orientation of the SL-EGF relative to
      the membrane normal axis. The rotational mobilities of the two rotational species
      are consistent with monomers and dimers or somewhat larger oligomers, such as
      trimers or tetramers, arguing against a role for higher order receptor clustering
      in receptor activation. Considering the two minima and previous observations that
      A431 membrane vesicles contain two distinguishable ligand-binding populations,
      the ST-EPR spectra were fit with a model having two uniaxial rotating species.
      This yielded two components that were similar to those obtained from the two
      original one-component fits, either fast or slow rotational mobility, with
      different orientations. The model-dependent results obtained suggest that there
      are potential conformational and rotational differences in the two populations
      and provide a plausible description for the origin of high- and low-affinity EGF
      binding sites that can be tested in future experiments.

PMID- 11827543
TI  - Specific binding of Ro 09-0198 (cinnamycin) to phosphatidylethanolamine: a
      thermodynamic analysis.
AB  - Ro 09-0198 (cinnamycin) is a tetracyclic peptide antibiotic that is used to
      monitor the transbilayer movement of phosphatidylethanolamine (PE) in biological
      membranes during cell division and apoptosis. The molecule is one of the very
      rare examples where a small peptide binds specifically to a particular lipid. In
      model membranes and biological membranes containing phosphatidylethanolamine, Ro
      09-0198 forms a 1:1 complex with this lipid. We have measured the thermodynamic
      parameters of complex formation with high sensitivity isothermal titration
      calorimetry and have investigated the structural consequences with deuterium and
      phosphorus solid-state NMR. Complex formation is characterized by a large binding
      constant, K0, of 10(7) to 10(8) M(-1), depending on the experimental conditions.
      The reaction enthalpy, DeltaHdegrees, varies between zero at 10 degrees C to
      strongly exothermic -10 kcal/mol at 50 degrees C. For large vesicles with a
      diameter of approximately 100 nm, DeltaHdegrees decreases linearly with
      temperature and the molar heat capacity of complex formation can be evaluated as
      = -245 cal/mol, indicating a hydrophobic binding mechanism. The free energy of
      binding is DeltaGdegrees = -10.5 kcal/mol and shows only little temperature
      dependence. The constancy of DeltaGdegrees together with the distinct temperature
      dependence of DeltaHdegrees provide evidence for an entropy-enthalpy compensation
      mechanism: at 10 degrees C, complex formation is completely entropy-driven, at 50
      degrees C it is enthalpy-driven. Varying the PE fatty acid chain-length between 6
      and 18 carbon atoms produces similar binding constants and DeltaHdegrees values.
      Addition of Ro 09-0198 to PE containing bilayers eliminates the typical bilayer
      structure and produces 2H- and 31P-NMR spectra characteristic of slow isotropic
      tumbling. This reorganization of the lipid matrix is not limited to PE but also
      includes other lipids.

PMID- 11827544
TI  - Chemical modification of amine groups on PS II protein(s) retards photoassembly
      of the photosynthetic water-oxidizing complex.
AB  - Four Mn atoms function as catalysts in the water-oxidizing complex located on the
      oxidizing side of PS II. We have studied the involvement of amine groups of the
      PS II proteins in photoligation of Mn2+ to the apo water-oxidizing complex, using
      the combined techniques of photoactivation and chemical modification with the
      modifiers methyl acetimidate (MAI), acetic acid N-hydroxysuccinimide ester (NHS),
      and 2,4,6-trinitrobenzenesulfonic acid (TNBS). Chemical modification of
      hydroxylamine-treated PS II core complexes decreased their capacity for
      restoration of oxygen evolution and photoligation of Mn2+ to the apo water
      oxidizing complex (WOC), but did not affect their electron transfer activity in
      the vicinity of PS II. The number of functional high-affinity Mn-binding sites,
      but not of low-affinity sites, was significantly modulated by chemical
      modification. Kinetic analysis of photoactivation with the repetitive flashes
      revealed that the intermediate generated during a photoactivation process was
      destabilized by the chemical modification. To identify which proteins possess the
      amine groups involved in ligation of functional Mn, we examined the difference in
      NHS biotinylation between PS II core complexes with and without the Mn cluster.
      NHS biotinylation resulting in altered ligation of functional Mn apparently
      occurred on three proteins: an antenna chlorophyll binding protein (CP47), a
      light-harvesting chlorophyll protein (CP29), and another chlorophyll binding
      protein (PS II-S). Of these proteins, only the Mn-dependent biotinylation of CP47
      was found to occur independently of the application of an NHS-masking
      concentration before removal of the functional Mn. These results suggest that
      lysyl residues of CP47, and perhaps also CP29 and PS II-S, function in direct
      photoligation of Mn2+ to the apo WOC.

PMID- 11827545
TI  - Magneto-optical measurements of the pigments in fully active photosystem II core
      complexes from plants.
AB  - Preparation of a minimum PSII core complex from spinach is described, containing
      four Mn per reaction center (RC) and exhibiting high O2 evolving activity
      [approximately 4000 micromol of O2 (mg of chl)(-1) x h(-1)]. The complex consists
      of the CP47 and CP43 chlorophyll binding proteins, the RC D1/D2 pair, the
      cytochrome b559 subunits, and the Mn-stabilizing psbO (33 kDa) protein, all
      present in the same stoichiometric amounts found in the parent PSII membranes.
      Several small subunits are also present. The cyt b559 content is 1.0 per RC in
      core complexes and PSII membranes. The total chlorophyll content is 32 chl a and
      <1 chl b per RC, the lowest yet reported for any active PSII preparation. The
      core complex exhibits the characteristic EPR signals seen in the S2 state of
      higher plant PSII. A procedure for preparing low-temperature samples of very high
      optical quality is developed, allowing detailed optical studies in the S1 and S2
      states of the system to be made. Optical absorption, CD, and MCD spectra reveal
      unprecedented detail, including a prominent, well-resolved feature at 683.5 nm
      (14630 cm(-1)) with a weaker partner at 187 cm(-1) to higher energy. On the basis
      of band intensity, CD, and MCD arguments, these features are identified as the
      exciton split components of P680 in an intact, active reaction center special
      pair. Comparisons are made with solubilized D1/D2/cyt b559 material and
      cyanobacterial PSII.

PMID- 11827546
TI  - An NADH-dependent bacterial thioredoxin reductase-like protein in conjunction
      with a glutaredoxin homologue form a unique peroxiredoxin (AhpC) reducing system
      in Clostridium pasteurianum.
AB  - Many eubacterial genomes including those of Salmonella typhimurium, Streptococcus
      mutans, and Thermus aquaticus encode a dedicated flavoprotein reductase (AhpF,
      Nox1, or PrxR) just downstream of the structural gene for their peroxiredoxin
      (Prx, AhpC) homologue to reduce the latter protein during turnover. In contrast,
      the obligate anaerobe Clostridium pasteurianum codes for a two-component reducing
      system upstream of the ahpC homologue. These three structural genes, herein
      designated cp34, cp9, and cp20, were previously identified upstream of the
      rubredoxin gene in C. pasteurianum, but were not linked to expression of the
      latter gene [Mathieu, I., and Meyer, J. (1993) FEMS Microbiol. Lett. 112, 223
      227]. cp34, cp9, and cp20 have been expressed in Escherichia coli, and their
      products have been purified and characterized. Cp34 and Cp9 together catalyze the
      NADH-dependent reduction of Cp20 to effect the reduction of various hydroperoxide
      substrates. Cp34, containing noncovalently bound FAD and a redox-active disulfide
      center, is an unusual member of the low-M(r) thioredoxin reductase (TrxR) family.
      Like Escherichia coli TrxR, Cp34 lacks the 200-residue N-terminal AhpC-reducing
      domain present in S. typhimurium AhpF. Although Cp34 is more similar to TrxR than
      to AhpF in sequence comparisons of the nucleotide-binding domains, experiments
      demonstrated that NADH was the preferred reductant (Km = 2.65 microM). Cp9 (a
      distant relative of bacterial glutaredoxins) is a direct electron acceptor for
      Cp34, possesses a redox-active CXXC active site, and mediates the transfer of
      electrons from Cp34 to several disulfide-containing substrates including 5,5'
      dithiobis(2-nitrobenzoic acid), insulin, and Cp20. These three proteins are
      proposed to play a vital role in the defense of C. pasteurianum against oxidative
      damage and may help compensate for the putative lack of catalase activity in this
      organism.

PMID- 11827547
TI  - Comparative study of the active site caging of serine proteases: thrombin and
      factor Xa.
AB  - Bovine thrombin and human factor Xa were acylated at their active site
      selectively with inhibitors derived from the parent compound 4-guanidinophenyl
      (E)-4-diethylamino-2-hydroxy-alpha-methylcinnamate hydrochloride, 1b. Peptidyl
      side chains were attached to the phenol ring via amide connection, which served
      as a recognition motif in inhibiting different serine proteases. Upon irradiation
      with 366 nm light, the trans-cinnamate attached to the active-site serine
      isomerizes to the cis isomer which then rapidly lactonizes to release the free
      enzyme. The peptidyl side chain sequences specific for each serine protease were
      revealed via constructing and screening a library of homologous compounds. This
      methodology may be applied to other proteases. One application based on enzyme
      specific, photoactivatable inhibitors is to isolate a designated active protease
      from a mixture of several proteases. Thus, a cinnamate inhibitor with a biotin
      moiety, 1d, was synthesized. A solution of enzyme-specific, biotinylated
      inhibitor was added into a mixture of proteases containing a target enzyme. The
      target enzyme was acylated at the active site and subsequently bore a biotin
      tail. An avidin column was used to separate the biotinylated enzyme from the
      unmodified ones, by a strong binding between biotin and avidin. After a brief
      irradiation on the avidin column, the retained enzymes were released from the
      biotin tag and eluted off the column. To demonstrate the idea, thrombin and
      factor Xa have been separated from each other by this strategy.

PMID- 11827548
TI  - The presence of the WGD motif in CC8 heterodimeric disintegrin increases its
      inhibitory effect on alphaII(b)beta3, alpha(v)beta3, and alpha5beta1 integrins.
AB  - Two highly homologous dimeric disintegrins, CC5 and CC8, have been isolated from
      the venom of the North African sand viper Cerastes cerastes. CC5 is a homodimer
      containing an RGD motif in its subunits. CC8 is a heterodimer. The CC8A and CC8B
      subunits contain RGD and WGD tripeptide sequence in their respective integrin
      binding loops. Both CC5 and CC8 inhibited platelet aggregation and the adhesion
      of cells expressing integrins alphaII(b)beta3, alpha(v)beta3, and alpha5beta1 to
      appropriate ligands. However, the inhibitory activity of CC8 was at least 1 order
      of magnitude higher than that of CC5. Enhanced activity of CC8 over CC5 was also
      observed in the induction of LIBS epitopes on beta1 and beta3 integrins.
      Synthetic peptides in which the arginyl residue of the RGD motif had been
      replaced with tryptophans exhibited increased inhibitory activity toward
      integrins alpha5beta1, alphaII(b)beta3, and alpha(v)beta3. Moreover, alanine
      substitution of the aspartic acid of the WGD motif of these peptides decreased
      their inhibitory ability, whereas the same substitution in the RGD sequence
      almost completely abolished the activity of the peptides. We conclude that the
      WGD motif enhances the inhibitory activity of disintegrins toward
      alphaII(b)beta3, alpha(v)beta3, and alpha5beta1 integrins.

PMID- 11827549
TI  - Testing of the portal hypothesis: analysis of a V32G, F57G, K58G mutant of the
      fatty acid binding protein of the murine adipocyte.
AB  - The portal region of fatty acid binding proteins is hypothesized to function as a
      dynamic aperture, controlling accessibility of external ligands to the internal
      fatty acid binding cavity. To test this hypothesis, a triple mutant of the murine
      FABP4 has been developed (V32G, F57G, K58G, referred to as the portal mutant)
      that is predicted to constitutively enlarge the opening due to a reduction in the
      molecular dimensions of the side chains of key portal amino acids. The portal
      mutant was purified from expressing Escherichia coli, its stability was
      evaluated, and the thermodynamics and kinetics of ligand binding were compared to
      that of wild-type protein. Introduction of the three amino acid substitutions
      caused no significant change in the stability of the protein with a free energy
      of unfolding of 13.7 kJ/mol as compared to 14.0 kJ/mol for the wild-type protein.
      The portal mutant exhibited a modest decrease (4-fold) in ligand binding affinity
      using the fluorescent probe 1-anilinonaphthalene-8-sulfonic acid (1,8-ANS) as a
      surrogate ligand. 1,8-ANS displacement assays revealed that the binding affinity
      for oleate increased from a K0.5 of 196 +/- 15 nM for the wild-type protein to
      165 +/- 8 for the portal mutant, while that for arachidonate decreased from the
      wild type of 186 +/- 11 nM to 418 +/- 26 nM for the portal mutant. To evaluate
      cavity accessibility, rate of 1,8-ANS binding was assessed between the portal and
      wild-type protein. Using equimolar amounts of ligand and protein at 4 degrees,
      1,8-ANS bound within the cavity to 95% saturation (t0.95) in 750 ms, while the
      mutant protein was fully modified in less than 1.4 ms. To independently evaluate
      cavity accessibility, modification of the sole protein cysteine residue, C117
      residing within the cavity near C2-C4 of the bound ligand, was monitored using
      5,5'-dithio-bis(2-nitrobenzoic acid) modification. The half time for modification
      (t0.5) for the wild-type protein was approximately 20 s, while that for V32G F57G
      K58G occurred in less than a second. As such, enlargement of the portal region of
      FABP4 markedly increased the accessibility of ligands to the cavity while having
      only modest effects on ligand affinity. Taken together, these data provide
      support for the portal region hypothesis and suggest dynamic fluctuations in this
      region regulate cavity access, but not ligand affinity or selectivity.

PMID- 11827550
TI  - Bleaching kinetics of artificial visual pigments with modifications near the ring
      polyene chain connection.
AB  - Absorbance difference spectra were recorded at 20 degrees C from 30 ns to
      milliseconds after photolysis of lauryl maltoside suspensions of artificial
      visual pigments derived from 9-cis isomers of 5-ethylretinal, 8,16-methanoretinal
      (a 6-s-trans-bicyclic analogue), or 5-demethyl-8-methylretinal. In all three
      pigments, the earliest intermediate that was detected had the characteristics of
      a mixture of bathorhodopsin and a blue-shifted intermediate, BSI, which is the
      first decay product of bathorhodopsin in bovine rhodopsin. The first decays
      resolved on the nanosecond time scale were the formation of the lumirhodopsin
      analogues. Subsequent decays were able to be fit with a mechanistic scheme which
      has been shown to apply to both membrane and detergent suspensions of rhodopsin.
      Large increases were seen in the amount of metarhodopsin I which appeared after
      photolysis of 5-ethylisorhodopsin and the bicyclic isorhodopsin analogue, while 5
      demethyl-8-methylisorhodopsin more closely followed native rhodopsin in decaying
      through meta I380, a 380 nm absorbing precursor to metarhodopsin II. In addition
      to forming more metarhodopsin I, the bicyclic analogue stabilized the
      metarhodopsin I-metarhodopsin II equilibrium similarly to what has been
      previously reported for 9-demethylrhodopsin in detergent, introducing the
      possibility that the bicyclic analogue could similarly be defective in transducin
      activation. These observations support the idea that long after initial
      photolysis, structural details of the retinylidene chromophore continue to play a
      decisive role in processes leading to the activated form, metarhodopsin II.

PMID- 11827551
TI  - Infrared studies of the CO-inhibited form of the Fe-only hydrogenase from
      Clostridium pasteurianum I: examination of its light sensitivity at cryogenic
      temperatures.
AB  - Infrared spectroscopy has been used to examine the oxidized and CO-inhibited
      forms of Fe-only hydrogenase I from Clostridium pasteurianum. For the oxidized
      enzyme, five bands are detected in the infrared spectral region between 2100 and
      1800 cm(-1). The pattern of infrared bands is consistent with the presence of two
      terminally coordinated carbon monoxide molecules, two terminally coordinated
      cyanide molecules, and one bridging carbon monoxide molecule, ligated to the Fe
      atoms of the active site [2Fe] subcluster. Infrared spectra of the carbon
      monoxide-inhibited state, prepared using both natural abundance CO and 13CO,
      indicate that the two terminally coordinated CO ligands that are intrinsic to the
      enzyme are coordinated to different Fe atoms of the active site [2Fe] subcluster.
      Irradiation of the CO-inhibited state at cryogenic temperatures gives rise to two
      species with dramatically different infrared spectra. The first species has an
      infrared spectrum identical to the spectrum of the oxidized enzyme, and can be
      assigned as arising from the photolysis of the exogenous CO from the active site.
      This species, which has been observed in X-ray crystallographic measurements
      [Lemon, B. J., and Peters, J. W. (2000) J. Am. Chem. Soc. 122, 3793], decays
      above 150 K. The second light-induced species decays above 80 K and is
      characterized by loss of the infrared band associated with the Fe bridging CO at
      1809 cm(-1). Potential models for the second photolysis event are discussed.

PMID- 11827552
TI  - Acid-induced changes in thermal stability and fusion activity of influenza
      hemagglutinin.
AB  - The conformational and thermal stability of full-length hemagglutinin (HA) of
      influenza virus (strain X31) has been investigated using a combination of
      differential scanning calorimetry (DSC), analytical ultracentrifugation,
      fluorescence, and circular dichroism (CD) spectroscopy as a function of pH. HA
      sediments as a rosette comprised of 5-6 trimers (31-35 S) over the pH range of
      7.4-5.4. The DSC profile of HA in the native state at pH 7.4 is characterized by
      a single cooperative endotherm with a transition temperature (Tm) of 66 degrees C
      and unfolding enthalpy (DeltaH(cal)) of 800 kcal x (mol of trimer)(-1). Upon
      acidification to pH 5.4, there is a significant decrease in the transition
      temperature (from 66 to 45 degrees C), unfolding enthalpy [from 800 to 260 kcal x
      (mol of trimer)(-1)], and DeltaH(cal)/DeltaH(vH) ratio (from 3.0 to approximately
      1.3). Whereas the far- and near-UV ellipticities are maintained over this pH
      range, there is an acid-induced increase in surface hydrophobicity and decrease
      in intrinsic tryptophanyl fluorescence. The major contribution to the DSC
      endotherm arises from unfolding HA1 domains. The relationship between acid
      induced changes in thermal stability and the fusion activity of HA has been
      examined by evaluating the kinetics and extent of fusion of influenza virus with
      erythrocytes over the temperature and pH range of the DSC measurements.
      Surprisingly, X31 influenza virus retains its fusion activity at acidic pH and
      temperatures significantly below the unfolding transition of HA. This finding is
      consistent with the notion that the fusion activity of influenza virus may
      involve structural changes of only a small fraction of HA molecules.

PMID- 11827553
TI  - Phosphorylation by LAMMER protein kinases: determination of a consensus site,
      identification of in vitro substrates, and implications for substrate
      preferences.
AB  - LAMMER protein kinases are ubiquitous throughout eukaryotes, including multiple
      paralogues in mammals. Members are characterized by similar overall structure and
      highly identical amino acid sequence motifs in catalytic subdomains essential for
      phosphotransfer and interaction with substrates. LAMMER kinases phosphorylate and
      regulate the activity of the SR protein class of pre-mRNA splicing components,
      both in vitro and in vivo. In this study, we define an optimum in vitro consensus
      phosphorylation site for three family members using an oriented degenerate
      peptide library approach. We also examine the substrate specificity and
      interactions of several LAMMER protein kinases from widely diverged species with
      potential substrates, including their own N-termini, predicted to be substrates
      by the peptide-based approach. Although the optimal in vitro consensus
      phosphorylation site for these kinases is remarkably similar for short peptides,
      distinct substrate preferences are revealed by in vitro phosphorylation of intact
      proteins. This finding suggests that these kinases may possess varied substrates
      in vivo, and thus the multiple LAMMER kinases present in higher eukaryotes may
      perform differentiable functions. These results further demonstrate that these
      kinases can phosphorylate a number of substrates in addition to SR proteins,
      suggesting that they may regulate multiple cellular processes, in addition to the
      alternative splicing of pre-mRNAs.

PMID- 11827554
TI  - Kinetic models of translocation, head-on collision, and DNA cleavage by type I
      restriction endonucleases.
AB  - Digestion of linear DNA by type I restriction endonucleases is generally
      activated following the head-on collision of two translocating enzymes. However,
      the resulting distributions of cleavage loci along the DNA vary with different
      enzymes; in some cases, cleavage is located in a discrete region midway between a
      pair of recognition sites while in other cases cleavage is broadly distributed
      and occurs at nearly every intervening locus. Statistical models for DNA
      translocation, collision, and cleavage are described that can account for these
      observations and that are generally applicable to other DNA-based motor proteins.
      If translocation is processive (stepping forward is significantly more likely
      than DNA dissociation), then the linear distribution of an ensemble of proteins
      can be described simply using a Poisson relationship. The pattern of cleavage
      sites resulting from collision between two processive type I enzymes over a
      distance d can then be described by a binomial distribution with a standard
      deviation 0.5 x d1/2. Alternatively, if translocation is nonprocessive (stepping
      forward or dissociating become equally likely events), the linear distribution is
      described by a continuum of populated states and is thus extended. Comparisons of
      model data to the kinetics of DNA translocation and cleavage discount the
      nonprocessive model. Instead, the observed differences between enzymes are due to
      asynchronous events that occur upon collision. Therefore, type I restriction
      enzymes can be described as having processive DNA translocation but, in some
      cases, nonprocessive DNA cleavage.

PMID- 11827555
TI  - Lipid rafts are enriched in arachidonic acid and plasmenylethanolamine and their
      composition is independent of caveolin-1 expression: a quantitative electrospray
      ionization/mass spectrometric analysis.
AB  - Lipid rafts are specialized cholesterol-enriched membrane domains that
      participate in cellular signaling processes. Caveolae are related domains that
      become invaginated due to the presence of the structural protein, caveolin-1. In
      this paper, we use electrospray ionization mass spectrometry (ESI/MS) to
      quantitatively compare the phospholipids present in plasma membranes and
      nondetergent lipid rafts from caveolin-1-expressing and nonexpressing cells.
      Lipid rafts are enriched in cholesterol and sphingomyelin as compared to the
      plasma membrane fraction. Expression of caveolin-1 increases the amount of
      cholesterol recovered in the lipid raft fraction but does not affect the relative
      proportions of the various phospholipid classes. Surprisingly, ESI/MS
      demonstrated that lipid rafts are enriched in plasmenylethanolamines,
      particularly those containing arachidonic acid. While the total content of
      anionic phospholipids was similar in plasma membranes and nondetergent lipid
      rafts, the latter were highly enriched in phosphatidylserine but relatively
      depleted in phosphatidylinositol. Detergent-resistant membranes made from the
      same cells showed a higher cholesterol content than nondetergent lipid rafts but
      were depleted in anionic phospholipids. In addition, these detergent-resistant
      membranes were not enriched in arachidonic acid-containing ethanolamine
      plasmalogens. These data provide insight into the structure of lipid rafts and
      identify potential new roles for these domains in signal transduction.

PMID- 11827556
TI  - Apolipoprotein A-I(Milano) and apolipoprotein A-I(Paris) exhibit an antioxidant
      activity distinct from that of wild-type apolipoprotein A-I.
AB  - Apolipoprotein A-I(Milano) (apoA-I(Milano)) and apoA-I(Paris) are rare cysteine
      variants of apoA-I that produce a HDL deficiency in the absence of cardiovascular
      disease in humans. This paradox provides the basis for the hypothesis that the
      cysteine variants possess a beneficial activity not associated with wild-type
      apoA-I (apoA-I(WT)). In this study, a unique antioxidant activity of apoA
      I(Milano) and apoA-I(Paris) is described. ApoA-I(Milano) was twice as effective
      as apoA-I(Paris) in preventing lipoxygenase-mediated oxidation of phospholipids,
      whereas apoA-I(WT) was poorly active. Antioxidant activity was observed using the
      monomeric form of the variants and was equally effective before and after
      initiation of oxidative events. ApoA-I(Milano) protected phospholipid from
      reactive oxygen species (ROS) generated via xanthine/xanthine oxidase (X/Xo) but
      failed to inhibit X/Xo-induced reduction of cytochrome c. These results indicate
      that apoA-I(Milano) was unable to directly quench ROS in the aqueous phase. There
      were no differences between lipid-free apoA-I(Milano,) apoA-I(Paris), and apoA
      I(WT) in mediating the efflux of cholesterol from macrophages, indicating that
      the cysteine variants interacted normally with the ABCA1 efflux pathway. The
      results indicate that incorporation of a free thiol within an amphipathic alpha
      helix of apoA-I confers an antioxidant activity distinct from that of apoA-I(WT).
      These studies are the first to relate gain of function to rare cysteine mutations
      in the apoA-I primary sequence.

PMID- 11827557
TI  - Oral loading with propafenone for conversion of recent-onset atrial fibrillation:
      a review on in-hospital treatment.
AB  - Atrial fibrillation (AF) is a very common arrhythmia. In order to treat acute AF
      rapidly, effective drug regimens are required. Propafenone is a class IC
      antiarrhythmic agent that is suitable for oral loading as it reaches peak plasma
      concentrations within 2 to 4 hours of administration. The use of propafenone
      loading in patients with AF must be based on appropriate patient selection in
      view of the negative inotropic effect and the potential proarrhythmic effects of
      the drug. A series of controlled trials in patients with recent-onset AF without
      heart failure who were hospitalised with enforced bed rest has shown that orally
      loaded propafenone (450 to 600 mg as single dose) exerts a relatively quick
      effect (within 3 to 4 hours) and a high rate of efficacy (72 to 78% within 8
      hours). A potentially harmful effect of class IC agents is the risk of
      transforming AF into atrial flutter (3.5 to 5% of patients). However, atrial
      flutter with 1 : 1 atrioventricular response was observed in only two of 709
      patients receiving propafenone (0.3% incidence). Nevertheless, the potential
      negative inotropic effect of propafenone demands careful patient selection, with
      systematic exclusion of patients with left ventricular dysfunction or congestive
      heart failure. Oral loading with propafenone can be considered as an episodic
      treatment in patients with AF recurrences, as has been proposed for other drugs
      in the past. However, the safety of oral loading with propafenone as an
      outpatient treatment in appropriately selected patients has to be assessed by
      appropriately designed prospective studies.

PMID- 11827558
TI  - Treatment options for vancomycin-resistant enterococcal infections.
AB  - Serious infection with vancomycin-resistant enterococci (VRE) usually occurs in
      patients with significantly compromised host defences and serious co-morbidities,
      and this magnifies the importance of effective antimicrobial treatment.
      Assessments of antibacterial efficacy against VRE have been hampered by the lack
      of a comparator treatment arm(s), complex treatment requirements including
      surgery, and advanced illness-severity associated with a high crude mortality.
      Treatment options include available agents which don't have a specific VRE
      approval (chloramphenicol, doxycycline, high-dose ampicillin or
      ampicillin/sulbactam), and nitrofurantoin (for lower urinary tract infection).
      The role of antimicrobial combinations that have shown in vitro or animal-model
      in vivo efficacy has yet to be established. Two novel antimicrobial agents
      (quinupristin/ dalfopristin and linezolid) have emerged as approved therapeutic
      options for vancomycin-resistant Enterococcus faecium on the basis of in vitro
      susceptibility and clinical efficacy from multicentre, pharmaceutical company
      sponsored clinical trials. Quinupristin/dalfopristin is a streptogramin, which
      impairs bacterial protein synthesis at both early peptide chain elongation and
      late peptide chain extrusion steps. It has bacteriostatic activity against
      vancomycin-resistant E. faecium [minimum concentration to inhibit growth of 90%
      of isolates (MIC(90)) = 2 microg/ml] but is not active against Enterococcus
      faecalis (MIC(90 )= 16 microg/ml). In a noncomparative, nonblind, emergency-use
      programme in patients who were infected with Gram-positive isolates resistant or
      refractory to conventional therapy or who were intolerant of conventional
      therapy, quinupristin/dalfopristin was administered at 7.5 mg/kg every 8 hours.
      The clinical response rate in the bacteriologically evaluable subset was 70.5%,
      and a 65.8% overall response (favourable clinical and bacteriological outcome)
      was observed. Resistance to quinupristin/dalfopristin on therapy was observed in
      6/338 (1.8%) of VRE strains. Myalgia/arthralgia was the most frequent treatment
      limiting adverse effect. In vitro studies which combine quinupristin/dalfopristin
      with ampicillin or doxycyline have shown enhanced killing effects against VRE;
      however, the clinical use of combined therapy remains unestablished. Linezolid,
      an oxazolidinone compound that acts by inhibiting the bacterial pre-translational
      initiation complex formation, has bacteriostatic activity against both vancomycin
      resistant E. faecium (MIC(90) = 2 to 4 microg/ml) and E. faecalis (MIC(90) = 2 to
      4 microg/ml). This agent was studied in a similar emergency use protocol for
      multi-resistant Gram-positive infections. 55 of 133 evaluable patients were
      infected with VRE. Cure rates for the most common sites were complicated skin and
      soft tissue 87.5% (7/8), primary bacteraemia 90.9% (10/11), peritonitis 91.7%
      (11/12), other abdominal/pelvic infections 91.7% (11/12), and catheter-related
      bacteraemia 100% (9/9). There was an all-site response rate of 92.6% (50/54). In
      a separate blinded, randomised, multicentre trial for VRE infection at a variety
      of sites, intravenous low dose linezolid (200mg every 12 hours) was compared to
      high dose therapy (600 mg every 12 hours) with optional conversion to oral
      administration. A positive dose response (although statistically nonsignificant)
      was seen with a 67% (39/58) and 52% (24/46) cure rate in the high- and low-dose
      groups, respectively. Adverse effects of linezolid therapy have been
      predominantly gastrointestinal (nausea, vomiting, diarrhoea), headache and taste
      alteration. Reports of thrombocytopenia appear to be limited to patients
      receiving somewhat longer courses of treatment (>14 to 21 days). Linezolid
      resistance (MIC > or = 8 microg/ml) has been reported in a small number of E.
      faecium strains which appears to be secondary to a base-pair mutation in the
      genome encoding for the bacterial 23S ribosome binding site. At present a
      comparative study between the two approved agents for VRE
      (quinupristin/dalfopristin and linezolid) has not been performed. Several
      investigational agents are currently in phase II or III trials for VRE infection.
      This category includes daptomycin (an acidic lipopeptide), oritavancin (LY
      333328; a glycopeptide), and tigilcycline (GAR-936; a novel analogue of
      minocycline). Finally, strategies to suppress or eradicate the VRE intestinal
      reservoir have been reported for the combination of oral doxycyline plus
      bacitracin and oral ramoplanin (a novel glycolipodepsipeptide). If successful, a
      likely application of such an approach is the reduction of VRE infection during
      high risk periods in high risk patient groups such as the post-chemotherapy
      neutropenic nadir or early post-solid abdominal organ transplantation.

PMID- 11827559
TI  - Rationale for fixed-dose combinations in the treatment of hypertension: the cycle
      repeats.
AB  - Single-drug therapy remains the preferred way to begin treatment of hypertension,
      although in many patients this is unable to bring blood pressure (BP) to goal
      levels. Single-drug therapy, even when maximally titrated, is at best only
      modestly effective in normalising BP in Stage-I or II hypertension, which
      represents the majority of the hypertensive population. It is increasingly
      appreciated that the elusive goal of a 'normal' BP is achieved only if multi-drug
      therapy is employed. This is especially so when considered in the context of
      today's lower BP goals. The options for multi-drug therapy are quite simple:
      either fixed-dose combination therapy or drugs added sequentially one after
      another to then arrive at an effective multi-drug regimen. Advocates exist for
      both approaches. A considerable legacy, dating to the 1950's, exists for fixed
      dose combination therapies. The rationale to this approach has remained constant.
      Fixed-dose combination therapy successfully reduces BP because two drugs, each
      typically working at a separate site, block different effector pathways. In
      addition, the second drug of such two-drug combinations may check counter
      regulatory system activity triggered by the other. For example, a diuretic and
      beta-blocker combination may find the diuretic correcting the salt-and-water
      retention which occasionally accompanies beta-blocker therapy. The pattern of
      adverse effects also differs with fixed-dose combination therapy, in part,
      because less drug is generally being given. In addition, one component of a fixed
      dose combination therapy can effectively counterbalance the tendency of the other
      to produce adverse effects. For example, the peripheral oedema, that accompanies
      calcium channel antagonist therapy, occurs less frequently when an ACE inhibitor
      is co-administered. ACE inhibitors improve, if not eliminate, the peripheral
      oedema associated with calcium channel antagonists because of their proven
      ability to cause venodilation. In addition, diuretic therapy-induced volume
      contraction may generate a state of secondary hyperaldosteronism and thereby
      electrolyte abnormalities such as hypokalaemia and/or hypomagnesaemia. In many
      cases, the co-administration of either an ACE inhibitor or an angiotensin II
      receptor blocker with a diuretic corrects the aforementioned electrolyte
      disturbances. Fixed-dose combination therapy has a proven record of reducing BP.
      This form of treatment has been available for close to a half-century. Over that
      period of time, many physicians have taken advantage of this therapeutic approach
      even when academic opinion was less than charitable to this concept. Academic
      opinion is rarely immutable and occasionally irrelevant to prescription practice.
      Prescription practice is driven by many considerations including ease of use,
      cost and tolerance of a therapy. Most importantly, the therapeutic pathway taken
      should successfully result in goal BP being reached in a large number of those
      treated. Unfortunately, despite the simplicity of the concept behind fixed-dose
      combination therapy, its success will ultimately rest on cost. If made truly cost
      competitive, it will gain an increasing share of the hypertensive market. If not,
      market forces will relegate it to a secondary role for hypertension treatment.

PMID- 11827562
TI  - Estradiol valerate/dienogest.
AB  - Estradiol valerate 2mg/dienogest 2mg is an oral estrogen/ progestogen formulation
      that has been approved throughout the European Union for the treatment of
      climacteric symptoms in postmenopausal women. Dienogest is a progestogen that
      combines the properties of both progesterone and 19-nortestosterone derivatives.
      It has moderate affinity for the progesterone receptor, significant
      antiproliferative and antiandrogenic activity, and produces secretory
      transformation of the endometrium. Estradiol valerate is an esterified form of
      natural 17beta-estradiol, the most potent endogenous human ovarian estrogen, and
      is hydrolysed to estradiol soon after oral administration. Results from a
      randomised, double-blind, multicentre trial showed that oral estradiol valerate
      2mg/dienogest 2mg and estradiol valerate 2mg/dienogest 3mg once daily for 1 year
      were each as effective as estradiol 2mg/estriol 1mg/norethisterone acetate 1mg in
      the treatment of climacteric symptoms in 581 postmenopausal women; reductions
      from baseline in Kupperman Index scores were 78.5, 74.5 and 75.0%, respectively.
      The number of days without any type of bleeding was lowest in patients treated
      with estradiol valerate 2mg/dienogest 2mg (8.7 days), and highest in the
      estradiol valerate 2mg/ dienogest 3mg group (12.1 days). During the twelfth month
      of treatment with estradiol valerate 2mg/dienogest 2mg, the percentage of
      patients who reported bleeding was 14.5%. Endometrial biopsy results were similar
      in patients treated with estradiol valerate 2mg/dienogest 2mg, estradiol valerate
      2mg/dienogest 3mg or estradiol 2mg/estriol 1mg/norethisterone acetate 1mg once
      daily for 1 year; 90.8, 87.4 and 87.5% of samples, respectively, contained
      atrophic material. Proliferative material was found in 4.2, 2.5 and 4.4% of the
      biopsies, respectively; there was no incidence of hyperplasia in any of the
      treatment groups. A noncomparative multicentre study in 1501 postmenopausal women
      demonstrated that adverse events associated with estradiol valerate 2mg/dienogest
      2mg once daily for 48 weeks included breakthrough bleeding, mastalgia, headache,
      abdominal pain, hypertension, thrush, migraine, weight gain, increase in
      endometrial thickness and metrorrhagia.

PMID- 11827561
TI  - Viral skin infections: diagnosis and treatment considerations.
AB  - Skin lesions are prominent features of many viral diseases. In some instances,
      characteristic skin lesions suggest a specific viral illness, the diagnosis of
      which can be quickly established by appropriate procedures. In addition to
      clinical manifestations, laboratory methods including virus isolation are used to
      diagnose viral infections. In viral diseases, prophylaxis has proved more
      successful than the specific treatment of established infection. However, recent
      progress in molecular biology has facilitated the development of new vaccines and
      new drugs to treat viral infections.

PMID- 11827560
TI  - Low molecular weight heparins: a guide to their optimum use in pregnancy.
AB  - The incidence of pulmonary embolism (PE) and venous thromboembolism (VTE) is
      higher in pregnant patients than in non-pregnant patients. The incidence of
      thrombosis in all pregnancies is reported to be between 0.05 and 1%, and an
      incidence as high as 3% may be present in women after caesarean section.
      Anticoagulant medication is prescribed during pregnancy in patients presenting
      with VTE, thrombophilia abnormalities, or a history of PE or VTE. Since
      unfractionated heparin (UH) does not cross the placental barrier, it has become
      the gold standard anticoagulant therapy during pregnancy. Oral anticoagulants may
      also be prescribed during the second trimester but they cross the placental
      barrier. Low molecular weight heparins (LMWH) are effective, easy to use and have
      good safety profiles. The practical conditions of use have yet to be validated
      for pregnancy settings. In the absence of an approved indication, LMWH use during
      pregnancy is therefore the responsibility of the practitioner. However, several
      studies on LMWH as prophylaxis for PE or VTE have shown that such products are
      effective with good safety. Moreover, LMWH use is associated with reduced
      frequencies of thrombocytopenia and osteoporosis compared with UH use. Very few
      studies on LMWH use for the treatment of PE or VTE during pregnancy have been
      published, but the safety of LMWH use in this setting appears to be good. The
      review of the use of LMWH in pregnancy settings includes recommendations on the
      practical conditions of use. In the absence of large-scale, randomised, double
      blind trials in such settings (which are needed), we propose the use of LMWH as
      prophylaxis for PE and VTE during pregnancy, but not for the treatment of these
      conditions. In prophylaxis settings, dalteparin sodium and enoxaparin sodium have
      been the most widely studied LMWH and we believe that priority should therefore
      be given to those products. Pending approval of LMWH for use in pregnancy, the
      use of LMWH off-label is the practitioner's responsibility.

PMID- 11827566
TI  - The EU White Paper: strategy for a future chemicals policy (an idea that must
      have seemed good at the time!).

PMID- 11827567
TI  - Alternatives to animal testing in the safety evaluation of products.
AB  - The conventional method for assessing the safety of products, ranging from
      pharmaceuticals to agrochemicals, biocides and industrial and household chemicals
      - including cosmetics - involves determining their toxicological properties by
      using experimental animals. The aim is to identify any possible adverse effects
      in humans by using these animal models. Providing safe products is undoubtedly of
      the utmost importance but, over the last decade or so, this aim has come into
      conflict with strong public opinion, especially in Europe, against animal
      testing. Industry, academia and the regulators have worked in partnership to find
      other ways of evaluating the safety of products, by non-animal testing, or at
      least by reducing the numbers of animals required and the severity of the tests
      in which they are used. There is a long way to go before products can be
      evaluated without any animal studies, and it may be that this laudable aim is an
      impossible dream. Nevertheless, considerable progress has been made by using a
      combination of in vitro tests and the prediction of properties based on chemical
      structure. The aim of this review is to describe these important and worthwhile
      developments in various areas of toxicological testing, with a focus on the
      European regulatory framework for general industrial and household chemicals.

PMID- 11827568
TI  - A comparative study of the toxicity of mercury dichloride and methylmercury,
      assayed by the Frog Embryo Teratogenesis Assay--Xenopus (FETAX).
AB  - The Frog Embryo Teratogenesis Assay-Xenopus (FETAX) is a powerful and flexible
      bioassay that makes use of the embryos of the anuran amphibian Xenopus laevis.
      The FETAX can detect xenobiotics that affect embryonic development, when
      mortality, teratogenicity and growth inhibition are used as endpoints. The FETAX
      was used to compare the embryotoxic and teratogenic potentials of two chemical
      species of mercury, inorganic mercury(II) chloride (HgCl2) and organic
      methylmercury chloride (MeHgCl). A higher toxicity of MeHgCl (the estimated
      median lethal concentration [LC50] and median teratogenic concentration [TC50]
      were 0.313microM and 0.236microM, respectively) over HgCl2, with estimated LC50
      and TC50 values of 0.601microM and 0.513microM, respectively). On the basis of
      these results, HgCl2 and MeHgCl can be classified as "slightly teratogenic
      compounds", as the ratio of LC50/TC50 is less than 1.5. There was a significant
      deviation from the commonly described monotonic behaviour of the concentration
      response curves, suggesting a hormetic effect of both species of mercury. Uptake
      experiments, followed by neutron activation analysis, showed a higher
      incorporation of mercury in embryos exposed to MeHgCl compared with those exposed
      to HgCl2. Interestingly, Hg- exposed embryos showed a higher content of selenium
      and zinc than did control embryos.

PMID- 11827565
TI  - Interferon-alpha-2b plus ribavirin: a review of its use in the management of
      chronic hepatitis C.
AB  - Relatively few patients (< or =20%) with chronic hepatitis C achieve a sustained
      virological response after interferon-alpha monotherapy. Hence, alternative
      treatment strategies such as the addition of the broad spectrum antiviral agent
      ribavirin to interferon-alpha-2b have been investigated. Combination therapy with
      subcutaneous interferon-alpha-2b [3 million units (MU) three times per week] plus
      oral ribavirin (1000 to 1200 mg/day) has proven effective in several well
      designed trials of 24 to 48 weeks' duration in adult patients with compensated
      chronic hepatitis C. Compared with interferon-alpha-2b (3 or 6 MU three times per
      week) with or without placebo, combination treatment with interferon-alpha-2b
      plus ribavirin significantly enhanced end-of-treatment and sustained virological
      and biochemical response rates in treatment-naive and treatment-experienced
      patients [sustained virological response rates in treatment-naive recipients (6
      to 19% vs 31 to 43% of patients); sustained overall (virological plus
      biochemical) response rates in nonresponders to (1 vs 14%) or relapsers (4 to 5%
      vs 30 to 44%) after previous interferon-alpha monotherapy]. Forty-eight weeks of
      combination therapy was superior to 24 weeks in treatment-naive patients infected
      with hepatitis virus C (HCV) genotype 1, whereas response rates were similar at
      24 and 48 weeks in those infected with other HCV genotypes. Furthermore, there
      were marked improvements in histological inflammatory scores in patients who
      responded to treatment with either interferon-alpha-2b plus ribavirin or
      interferon-alpha-2b alone. Although adverse events associated with either drug
      during combination therapy occurred frequently, these were generally mild to
      moderate in intensity and were consistent with those reported for each individual
      agent. Twenty-six percent of patients required dosage modifications of one or
      both drugs during combination therapy. CONCLUSIONS: Interferon-alpha-2b plus
      ribavirin is an efficacious first- and second-line therapy in adult patients with
      compensated chronic hepatitis C, significantly improving sustained virological
      and biochemical responses versus interferon-alpha-2b monotherapy. The
      tolerability profile of interferon-alpha-2b plus ribavirin therapy is consistent
      with the individual profiles of these agents with no evidence of additive
      effects. The place of interferon-alpha-2b plus ribavirin combination therapy in
      relation to newer agents, including pegylated interferons-alpha and other
      multidrug regimens, remains to be determined in this rapidly evolving area of
      therapeutic management. Currently, combination therapy with interferon-alpha-2b
      plus ribavirin is recommended as first-line therapy for patients with chronic
      hepatitis C and compensated liver disease, and is an option for use as second
      line therapy in those who have relapsed after, or failed to respond to, previous
      treatment with interferon-alpha.

PMID- 11827569
TI  - Use of a cell transformation assay with established cell lines, and a metabolic
      cooperation assay with V79 cells for the detection of tumour promoters: a review.
AB  - Extensive studies on the safety evaluation of chemicals have indicated that a
      considerable number of non-genotoxic chemicals are carcinogenic. Tumour promoters
      are likely to be among these non-genotoxic carcinogens, and their detection is
      considered to be an important approach to the prevention of cancer. In this
      review, the results are summarised for in vitro transformation assays involving
      established cell lines, and for an assay for inhibition of gap junctional
      intercellular communication for the detection of tumour promoters, which involves
      V79 cells. Although the number of chemicals examined is still too small to permit
      a full evaluation of the correlation between in vitro cell transformation and in
      vivo carcinogenicity, it is clear that the sensitivity of the focus formation
      assay is very high. In the case of the metabolic cooperation assay, the
      sensitivity appears to be rather poor, but the assay can be considered to be
      useful because of its simple procedure and its considerable database. These in
      vitro assays for tumour promoters are recommended as useful tools for the
      detection of non-genotoxic carcinogens.

PMID- 11827570
TI  - Cystathionine pathway-dependent cytotoxicities of diethyl maleate and diamide in
      rat and human hepatoma-derived cell cultures.
AB  - Glutathione (GSH) plays a role in many toxicologically important metabolic
      processes. It was previously established that L-buthionine S,R-sulphoximine
      (BSO), a specific inhibitor of (- glutamylcysteine synthetase, reduces the GSH
      content more efficiently in rat (Fa32) than in human (HEp-G2) hepatoma-derived
      cells. We therefore investigated whether the cystathionase inhibitor
      propargylglycine (PPG) could further decrease the BSO-induced GSH depletion in
      HEp-G2 cells. The influence of the cystathionine precursors N-acetylmethionine,
      methionine and homocysteine on the cytotoxicity of diethyl maleate (DEM) and
      diamide [1,1'-azobis(N,N-dimethylformamide)] was also investigated. PPG reduced
      the GSH content in both cell lines. A further GSH decrease in HEp-G2 was obtained
      when using a BSO + PPG combination containing relatively high concentrations of
      PPG. BSO diminished the toxicity of PPG. Homocysteine was the most efficacious of
      the tested cystathionine precursors in increasing the GSH content and reducing
      the cytotoxicity of DEM and diamide in Fa32 and HEp-G2 cells.

PMID- 11827571
TI  - Cytostatic properties of a novel compound derived from Penicillium pinophilum: an
      in vitro study.
AB  - 3-O-Methylfunicone (OMF), a secondary metabolite produced by Penicillium
      pinophilum, inhibits the in vitro growth of plant pathogenic fungi. This specific
      property suggested that the compound could be used against other fungal
      pathogenic activities, including dermatological ones. However, for such
      applications, toxicological side-effects should be taken into account, in order
      to prevent other types of risk to mammalian cells. Therefore, investigations were
      made of the basic toxicity of OMF toward a human tumour cell line. The compound
      was found to have a cytostatic effect, which represents a counter-indication to
      its use as a therapeutic agent in dermatology, but suggests that it may have
      potential as an anti-tumour agent. This study confirmed the validity of in vitro
      systems for preliminary assays on new compounds, in order to avoid the use of
      animals in toxicological studies.

PMID- 11827572
TI  - Detection of the embryotoxic potential of cyclophosphamide by using a combined
      system of metabolic competent cells and embryonic stem cells.
AB  - In order to develop a method for detecting metabolism-mediated embryotoxicity,
      differentiating embryonic stem (ES) cells were exposed to the well-known
      proteratogen, cyclophosphamide (CPA). CPA was tested in a scientifically
      validated embryonic stem-cell test (EST), and in the newly developed reporter
      gene assay for developmental cardiotoxicity. Both assays gave false-negative
      results. Because no metabolic competence (cytochrome P450 [CYP] activity) was
      found in the ES cells under the selected culture conditions, a simple
      biotransformation system was combined with the reporter-gene assay. As the
      metabolic pathway of CPA is well characterised, the genetically engineered
      mammalian cell line V79, transfected with CYP2B1 cDNA, was selected as a
      biotransformation system. CYP2B1 is responsible for transforming CPA into
      teratogenically active metabolites. The supernatants of genetically engineered
      V79 cells were analysed in the reporter-gene assay for developmental
      cardiotoxicity. In preliminary experiments, the combined system was able to
      detect the embryotoxic potential of the proteratogen, CPA.

PMID- 11827573
TI  - Use of the SOS-chromotest spot assay as a screening system for detecting
      genotoxic compounds in crude plant extracts.
AB  - An SOS-chromotest spot assay was used to detect genotoxic compounds in crude
      plant extracts. The method allows simultaneous testing of extracts from different
      species in either a liquid or a solid crystalline form. Extracts from two species
      of the genus Senna, native to the state of Morelos, Mexico, were assayed. Four
      genotoxic compounds were isolated, and were identified as quercetin and rutin
      from S. wislizeni, and 5,7-di- O-methylrutin and 5,7-di-O-methylquercetin from S.
      skinneri. The SOS-chromotest spot assay proved to be useful for activity- guided
      fractionation at the beginning of screening for genotoxic compounds in crude
      plant extracts.

PMID- 11827574
TI  - ECVAM's contributions to the implementation of the Three Rs in the production and
      quality control of biologicals.
AB  - A summary is presented of the activities initiated, and the progress achieved,
      between April 1993 and December 2001 in implementing the Three Rs in one of the
      main priority areas of the European Centre for the Validation of Alternative
      Methods (ECVAM) - the production and quality control of biologicals. These have
      included organising eight key workshops, and financial contributions to, and
      sponsorship of, relevant international workshops, symposia and conferences.
      Noteworthy activities include financial support and/or participation in a number
      of prevalidation and validation studies. These involved alternative methods for
      the batch potency testing of: human tetanus vaccines; human and veterinary
      tetanus antisera and immunoglobulin; rabies vaccines; Leptospira hardjo vaccines;
      Clostridium perfringens vaccines; and erysipelas vaccines. They also involved a
      cell culture test for specific toxicity testing of diphtheria toxoid vaccines. In
      addition, ECVAM funded a study on the use of humane endpoints for vaccine quality
      control tests involving severe suffering, such as the potency testing of
      erysipelas, rabies and pertussis vaccines. ECVAM has also contributed financially
      to the compilation of manuals and expert reports, and to training in test
      methods. Following the report of an ECVAM Task Force, ECVAM financially supported
      the prevalidation of some in vitro methods for the potency testing of a
      recombinant hormone. A proposal is presented for promotion of regulatory
      acceptance, and suggestions are made for possible future activities.

PMID- 11827575
TI  - Follow-up to the ECVAM prevalidation study on in vitro tests for acute skin
      irritation. The European Centre for the Validation of Alternative Methods Skin
      Irritation Task Force report 2.
AB  - The European Centre for the Validation of Alternative Methods (ECVAM) Skin
      Irritation Task Force was established in 1996, to review the status of the
      development and validation of alternative tests for skin irritation and
      corrosion, and to identify appropriate non-animal tests for predicting human skin
      irritation that were sufficiently well-developed to be prevalidated and validated
      by ECVAM. The EpiDerm method, based on a reconstituted human skin model, was
      proposed as being sufficiently well advanced to enter a prevalidation (PV) study.
      Based on a review of test protocols, prediction models (PMs), and data submitted
      by test developers on ten specified chemicals, with 20% sodium lauryl sulphate as
      a reference standard, the task force recommended the inclusion of four other
      tests: EPISKIN and PREDISKIN, based on reconstituted human epidermis or on human
      skin; the non-perfused pig-ear test, based on pig skin; and the skin integrity
      function test (SIFT), with ex vivo mouse skin. The prevalidation study on these
      methods was funded by ECVAM, and took place during 1999-2000. The outcome of the
      PV study was that none of the methods was ready to enter a formal validation
      study, and that the protocols and PMs of the methods had to be improved in order
      to increase their predictive abilities. Improved protocols and PMs for the
      EpiDerm and EPISKIN methods, the pig ear test, and the SIFT were presented at an
      extended Task Force meeting held in May 2001. It was agreed that, in the short
      term, the performance of the revised and harmonised EpiDerm and EPISKIN methods,
      as well as the modified SIFT, should be evaluated in a further study with a new
      set of 20 test chemicals. In addition, it was decided that the SIFT and the pig
      ear test would be compared to see if common endpoints (transepidermal water loss,
      methyl green-pyronine stain) could be identified.

PMID- 11827576
TI  - A critique of the animal procedures committee report on biotechnology.

PMID- 11827577
TI  - Ear nose and throat diseases in the Bedouin of the South Sinai Desert: a cross
      sectional survey and discussion of healthcare needs.
AB  - In the summer of 2000, a team of medical and affiliated workers visited the South
      Sinai Desert to assess the medical problems and needs of the Bedouin population.
      This paper reports on the ENT diseases of this population, and discusses their
      healthcare needs.

PMID- 11827578
TI  - Osseointegrated implants in the management of childhood ear abnormalities: with
      particular emphasis on complications.
AB  - Little has been published about the difficulties encountered during the insertion
      of osseointegrated implants for the attachment of bone anchored hearing aids
      (BAHA) and auricular prostheses in children. This study examines this issue in
      the first 51 children implanted at our centre. During surgery, the most common
      problem encountered was the presence of thin bone resulting in incomplete
      insertion of fixtures. Five fixtures had failed to integrate and six fixtures
      were lost in the long-term, however, only five children required revision
      surgery. The reason why few patients require revision was due to the judicious
      insertion of 'sleeper' fixtures. At follow-up, seven children required
      counselling for psychological problems. It is apparent from this study that
      osseointegrated implants in children are associated with difficulties, re
      emphasizing that a paediatric osseointegration programme requires significant
      investment, and should only be undertaken by institutions that are committed to
      its success.

PMID- 11827579
TI  - Congenital conductive hearing loss.
AB  - Congenital conductive hearing loss due to ossicular deformities can be treated by
      either rehabilitation with a hearing aid or surgical reconstruction. We present
      the results of exploratory tympanotomy performed in a large paediatric
      otolaryngology centre in 67 patients with non-serous congenital conductive
      hearing loss. Forty-two children had malformation of one or more ossicles without
      fixation of the stapes, and 19 had fixed stapes. In 26 cases, the surgeon decided
      not to perform surgical correction. Seven operated patients were lost to follow
      up. As a group, 47 per cent of the patients who underwent reconstruction showed
      no significant benefit from surgery, with post-operative air-bone gaps (ABG)
      greater than 30 dB. Assessment of the results by pathology showed that 64 per
      cent of the patients with mobile stapes had an air-bone gap within 30 dB compared
      to only 33 per cent of the patients with fixed stapes. One patient sustained
      severe sensorineural loss after the procedure. Considering that exploratory
      tympanotomy is a relatively minimal, benign procedure but that findings during
      exploration may exclude the option of reconstruction (in 39 per cent of our
      patients), we suggest exploring the ear, but in a more realistic, informed way.

PMID- 11827580
TI  - A comparison of the user-friendliness of hydroxyapatite and titanium ossicular
      prostheses.
AB  - Both hydroxyapatite (Ha) and titanium (Ti) are well-accepted alloplastic
      materials for ossicular prostheses. Many different designs of Ha and Ti
      prostheses are presently available. Fourteen surgeons of different seniority and
      surgical experience were asked to 'test-drive' four different types of ossicular
      prostheses in cadaveric temporal bones to investigate the user-friendliness of
      these protheses. The Goldenberg design Ha incus prosthesis and the Dusseldorf
      design Bell Ti prosthesis were used as partial ossicular replacement prostheses
      (PORP). The Richards design Ha incus-stapes prosthesis and the Dusseldorf design
      Aerial Ti prosthesis were used as a total ossicular replacement prostheses
      (TORP). Nine out of 14 surgeons found the Ha PORP to be more user-friendly
      because of the notch design in the head. The Ti prosthesis was found to be more
      difficult to manipulate because it was too light. Half of the surgeons preferred
      the Ti TORP because of the open design of the top-plate. The Ha TORP was thought
      to be too top-heavy and to have a tendency to fall over.

PMID- 11827581
TI  - Ear involvement in systemic lupus erythematosus patients: a comparative study.
AB  - Ear damage in systemic lupus erythematosus (SLE) patients has been occasionally
      reported but the frequency and the mechanisms of ear involvement are not well
      documented. In an attempt to investigate the presence of hearing loss and the
      possible causes for it we prospectively evaluated 43 SLE patients. All patients
      underwent a complete ear-nose-throat physical examination and audiological
      evaluation with pure tone, impedance and speech audiometry. In addition, systemic
      manifestations of the disease and drug therapy were recorded. Finally, all
      patients were tested for the presence of autoantibodies. The results were
      compared with those of 50 age-matched healthy subjects. Hearing loss (HL) was
      found in nine patients (22.5 per cent). More specifically, eight patients
      presented sensorineural hearing loss (SNHL) (21.5 per cent) and only one had
      conductive hearing loss (CHL) (2.63 per cent). From the patients with SNHL, one
      had bilateral symmetrical damage, four had bilateral but no symmetrical damage
      and three patients showed unilateral SNHL. Finally, the patient with CHL had
      unilateral involvement. There were no statistically significant differences
      between patients with HL and those without regarding age, disease duration,
      clinical disease manifestations, autoantibody profile and drug therapy. In
      conclusion, one fourth of our SLE patients presented HL, expressed as SNHL
      affecting mainly the middle and high frequencies, while only one patient had CHL.
      This is a lower percentage of ear involvement in SLE than that reported by other
      investigators. The mechanism of ear damage remains unknown. Thus, additional
      prospective studies are needed to elucidate its pathogenesis.

PMID- 11827582
TI  - A randomized control trial of post-operative care following endoscopic sinus
      surgery: debridement versus no debridement.
AB  - Endoscopic sinus surgery (ESS) has undergone exponential growth worldwide in the
      last decade. It is now accepted as a safe and effective means of treating
      sinonasal disease. The purpose of this study was to determine whether post
      operative debridement is necessary after ESS. Seventeen patients undergoing
      bilateral primary ESS were randomized to receive debridement of either the left
      or right ethmoid cavity. All patients included in the study had symmetrical
      disease. Saline douches and all other concomitant treatments were delivered
      bilaterally. Outcome measures were based on regular symptom scores and surgeons'
      semi-quantitative assessment of the debrided and non-debrided cavities, over a
      three-month period. Analysis of adhesion rates, healing and symptom scores showed
      no statistically significant difference between the two groups. In conclusion,
      this study did not demonstrate significant benefit from post-operative ESS cavity
      debridement, at least with regard to cavity healing. This should be considered a
      pilot study and therefore limited conclusions can be drawn. Further work is
      needed to determine the optimum post-operative care for ESS.

PMID- 11827583
TI  - Some risk factors for refractory chronic sinusitis: an immunohistochemical and
      electron microscopic study.
AB  - The goal of the present work was to investigate possible risk factors for the
      poor response of some cases of chronic sinusitis to endoscopic sinus surgery in
      spite of the precision of the surgical technique. Eleven adult patients who were
      scheduled for revision endoscopic sinus surgery underwent a complete allergy
      workup. At the time of surgery, a tiny biopsy was taken from the maxillary sinus
      mucosa close to the middle turbinate. The specimens were processed for
      histochemical and transmission electron microscopic examination. Six patients (55
      per cent) proved to be allergic. Their sinus mucosa showed eosinophilic
      infiltration (6.1 cells/mm(2)), and mast cell degranulation. This proves that
      allergens can reach the sinus mucosa and have a direct impact on it. Another
      three patients (27 per cent) were non-allergic but exhibited mucosal eosinophilia
      (5.0 cells/mm(2)), and two of them showed mast cell degranulation. These patients
      were diagnosed as having nonallergic rhinosinusitis with eosinophilia (NARSE).
      The nasal mucosa of the remaining two patients did not reveal any characteristic
      pathological findings, and no pathologic diagnosis could be established for them.
      None of the patients showed electron microscopic evidence of purulent
      inflammatory changes, and the bacterial cultures recovered normal respiratory
      flora in nine patients (82 per cent). The present research spotlights the
      importance of allergy and nonallergic eosinophilic infiltration of the mucosa as
      possible risk factors that may degrade the results of endoscopic sinus procedures
      and discusses some pertinent pathological and clinical aspects.

PMID- 11827584
TI  - Medium-term outcome of palatal surgery for snoring using the Somnus unit.
AB  - The aim of this study was to retrospectively survey patients who had undergone
      radiofrequency ablation of the soft palate for snoring complaints. Fifty-nine
      patients who had undergone radiofrequency ablation were sent an anonymous
      questionnaire to assess snoring (using visual analogue scales), pain and
      satisfaction with the procedure. Sixty-one per cent of the group returned the
      questionnaire. The mean time since operation was 17.5 months. Taking an
      improvement in snoring of 50 per cent or greater as a successful operation,
      snoring improvement occurred in 22 per cent. Post-operative pain was minimal with
      a median pain score of zero. Information was requested on whether the patient
      would undergo this procedure again, 50 per cent responded that they would and 44
      per cent would advise a friend in the same situation to have this procedure.
      Radiofrequency ablation of the soft palate, as in other forms of surgery for
      snoring, seems to have a relapse rate over the long-term.

PMID- 11827585
TI  - Malignant sialogenic tumours of the larynx.
AB  - Laryngeal manifestations of malignant sialogenic neoplasias are rare. This paper
      documents the clinical features, treatment, biological behaviour and prognosis of
      15 cases of malignant sialogenic tumours of the larynx that were reviewed in a
      retrospective clinical and histopathological study. The 15 cases of malignant
      sialogenic tumours of the larynx were diagnosed at the University Hospital,
      Eppendorf, over a period of 33 years (1965-1998). Forty per cent were adenoid
      cystic carcinomas, 33 per cent mucoepidermoid carcinomas and 27 per cent were
      poorly differentiated adenocarcinomas. Local tumour resection, if necessary in
      combination with bilateral neck dissection and post-operative radiotherapy, was
      associated with a five-year survival rate in 80 per cent of the mucoepidermoid
      carcinoma cases. Adenoid cystic carcinoma was associated with a less favourable
      five-year survival rate of 33 per cent. Low-differentiated adenocarcinomas were
      associated with the least favourable prognosis with a five-year survival rate (25
      per cent). The prognosis for these tumours is thus poorer than for squamous cell
      carcinomas with the same localization and TNM status.

PMID- 11827586
TI  - Novel use of nebulised adrenaline in the treatment of secondary oropharyngeal
      haemorrhage.
AB  - We report the use of nebulised adrenaline in the treatment of secondary
      oropharyngeal haemorrhage. Cases involving two adults and one child are presented
      to illustrate the usefulness of this technique in helping to achieve haemostasis
      without the need for a general anaesthetic. The mechanisms of the haemostatic
      action of adrenaline are also explored. We believe that in selected cases
      nebulised adrenaline is both safe, effective and easily tolerated and represents
      a useful additional tool in the treatment of oropharyngeal haemorrhage.

PMID- 11827587
TI  - Conductive hearing loss associated with Kallmann's syndrome.
AB  - The association of Kallmann's syndrome with conductive hearing loss has not
      previously been described. We report the findings at tympanotomy in three ears of
      patients with Kallmann's syndrome and conductive deafness. The literature related
      to this topic is reviewed, and the treatment of these patients is discussed.

PMID- 11827588
TI  - Old age presentation of the Dandy-Walker syndrome associated with unilateral
      sudden sensorineural deafness and vertigo.
AB  - Adult presentation of the Dandy-Walker syndrome is extremely rare. We report a
      case where the patient was first diagnosed at 75 years of age because of sudden
      onset of unilateral senorineural deafness and episodic vertigo. He remained well
      for a further three years until developing the more classical adult presenting
      features of cognitive impairment, disordered gait and ataxia. The radiological
      and otological investigative findings are discussed, together with their
      implications.

PMID- 11827589
TI  - Facial nerve paralysis and meningioma of the internal auditory canal.
AB  - Pathological lesions confined to the internal auditory canal (IAC) commonly
      present with cochleovestibular symptoms; sensorineural hearing loss, tinnitus and
      balance disturbance. The commonest lesion of the IAC is vestibular schwannoma.
      Other lesions include meningioma, facial neuroma, cavernous haemangioma, lipoma
      and arachnoid cyst. Presentation with facial palsy and an intracanalicular lesion
      is suggestive of pathology other than acoustic neuroma. Magnetic resonance
      imaging (MRI) cannot reliably distinguish intracanalicular vestibular schwannomas
      from meningiomas. Particular care is required for surgery of these lesions: the
      facial nerve typically does not lie in a protected anterior position within the
      IAC.

PMID- 11827591
TI  - Sleep apnoea of unusual origin.
AB  - A 72-year-old man presented with a history of progressive sleep apnoea. The cause
      was a large superior laryngeal nerve schwannoma arising in the left
      parapharyngeal space. This had a ball-valve effect on the laryngeal inlet.
      Superior laryngeal nerve schwannomas are very rare. No documented case has
      presented with obstructive sleep apnoea before.

PMID- 11827590
TI  - Maxillary sinus hypoplasia.
AB  - Functional endoscopic sinus surgery (FESS) is now a routine surgical procedure
      performed all around the world. A pre-operative computed tomography (CT) scan is
      considered mandatory in most countries where these are available but there are
      still some surgeons who question the need for imaging especially in patients due
      to undergo limited FESS or middle meatal antrostomy. There are excellent papers,
      describing how to read scans looking for anatomical abnormalities, but
      unfortunately their description of maxillary sinus hypoplasia and the associated
      uncinate process deformities are limited. This article describes two cases, one
      of unilateral and one of bilateral maxillary sinus hypopolasia (MSH) and
      discusses their implications. Awareness of these anatomical variants is crucial
      to avoid orbital complications.

PMID- 11827592
TI  - Laryngeal gout.
AB  - A review of the literature reveals only 12 reported cases of laryngeal gout. We
      describe three further cases of laryngeal gout, the largest series ever
      published. The first case is previously undescribed acute gouty
      cricoarytenoiditis resulting in acute airway embarrassment requiring tracheotomy,
      and then we describe two cases of chronic tophaceous involvement of the thyroid
      lamina with computed tomography (CT) images of this process. The paucity of
      literature on this subject may not only be due to rarity but also lack of
      clinical awareness. Gouty involvement of the larynx must be considered in any
      patient with a history of gout who presents with hoarseness, odynophagia,
      dysphagia, stridor or neck lump. Acute airway compromise may require tracheotomy,
      whereas chronic airway problems may necessitate endoscopic tophi removal,
      lateralization procedures or even permanent tracheostomy.

PMID- 11827593
TI  - Sustained complete remission of stage IV carcinoma of the pyriform fossa
      following chemotherapy.
AB  - Tumours of the hypopharynx continue to have one of the most dismal prognoses of
      all tumours of the upper aerodigestive tract. These tumours are frequently
      advanced at the time of diagnosis. They have a particularly high propensity for
      lymphatic spread. Treatment, thus appears difficult from the outset. Although
      therapeutic protocols have improved, their often radical nature is synonymous
      with poor tolerance. With neoadjuvant chemotherapy and reconstructive surgery,
      cure has become a possibility for an increasing number of patients. However,
      sustained long-term remission following chemotherapy alone for advanced
      hypopharyngeal tumours has seldom been recorded.

PMID- 11827594
TI  - Palate ulcer due to mucormycosis.
AB  - Mucormycosis is caused by fungi of the order Mucorales and is one of the most
      rapidly fatal fungal infections known to man. Rhinocerebral mucormycosis is the
      most common type and its extension to the orbit and brain is quite usual.
      Location of mucormycosis on the palate is a rare and late occurrence. A case of
      deep hard palate ulcer due to sinonasal mucormycosis in a 79-year-old man is
      reported. He was successfully treated with a combination of surgical debridement
      and systemic liposomal amphotericin B administration for six weeks. By presenting
      this case report we would like to point out that mucormycosis should be included
      in the differential diagnosis of hard palate ulcers.

PMID- 11827595
TI  - Migrating foreign body in the tracheobronchial tree: an unusual case of firework
      penetrating neck injury.
AB  - Firework injuries can manifest themselves in many different ways; usually as an
      explosive or burn injury. This case describes an unusual presentation of a
      firework penetrating injury resulting in a sharp coiled metal foreign body
      travelling through a small entry wound in the neck and subsequently lodging
      itself in the tracheobronchial tree. A foreign body such as this can potentially
      travel a considerable distance through the soft tissues and end up in an
      unsuspecting distant site. There must, therefore, be a high index of suspicion
      with the appropriate radiological investigations for appropriate management of
      such cases.

PMID- 11827596
TI  - Dermoid cyst of the infratemporal fossa.
AB  - Dermoid cysts are rare benign tumours, they represent the simplest form of
      teratoma. Approximately seven per cent affect the head and neck region, within
      this region they are frequently encountered in the area of the lateral eyebrow,
      the orbit and the nose. A case of a 17-year-old girl who developed a rapidly
      growing facial swelling due to an infratemporal fossa dermoid cyst is presented.
      A review of the literature using Medline has not revealed any previous reports of
      similar cases. The lesion was completely excised using a lateral approach to the
      infratemporal fossa.

PMID- 11827597
TI  - Primary hydatid cyst of the posterior cervical triangle.
AB  - Hydatid cysts in the cervical region are extremely rare. We report herein a case
      with a hydatid cyst that was primarily located in the posterior cervical triangle
      without any pulmonary or hepatic involvement. A hydatid cyst of the neck should
      be considered in the differential diagnosis of lesions in the cervical region, in
      endemic areas, so as to avoid any dangerous complications such as contamination
      and a fatal anaphylactic reaction.

PMID- 11827598
TI  - A primary glomus tumour of the facial nerve canal.
AB  - Glomus tumours can present in several sites in the head and neck. A red mass in
      the middle ear, visible on otoscopy generally indicates a glomus tympanicum or
      glomus jugulare. We present photographic and radiologic evidence of such a lesion
      arising from the course of the intra-tympanic facial nerve, the Fallopian canal,
      and review the differential diagnoses.

PMID- 11827599
TI  - Re: Supplement no. 26 (vol 114, April 2000).

PMID- 11827600
TI  - A 20-year study of an adolescent psychiatric clientele, with special reference to
      the age of onset.
AB  - During a period of 20 years (1968-1988) all inpatients admitted for the first
      time to the adolescent psychiatric unit in Copenhagen (n = 841) were classified
      in accordance with social and psychiatric variables, to describe the clientele as
      a group and, furthermore, to investigate changes occurring during that period.
      The total clientele had a broad age range (12-21 years), with as many as 36% less
      than 15 years old. Eleven percent of the patients had attempted suicide before
      admission. Fifty-six percent of the total group were diagnosed as psychotic or as
      borderline cases. The patients came predominantly from lower social levels, and
      almost half the group had a child debut defined as symptoms that had resulted in
      referral for further investigation during childhood. Moreover, among the
      schizophrenic patients 35% had an early onset. The age of onset may have some
      clinical significance, as this item was related to several sociodemographic
      variables. Finally, an increase in the rate of psychoses and lower social class
      was recorded during the period.

PMID- 11827601
TI  - A 10-year follow-up study of an adolescent psychiatric clientele and early
      predictors of readmission.
AB  - Over a period of 20 years (from 1968 to 1988) all inpatients (n = 839) who were
      admitted for the first time to the adolescent psychiatric unit in Copenhagen were
      registered, and 40 social and psychiatric variables were recorded, to investigate
      early predictors of later readmission. Overall, 44.8% of the patients were
      readmitted within a certain observation period (range, 1.5-21.5 years). Among a
      subsample of 488 patients (58%) who could be followed up for more than 10 years
      after their first admission 26% became heavy users of psychiatric services,
      defined as long-term inpatients or revolving-door patients. Severe early
      diagnoses (schizophrenia and affective psychoses) were strongly associated with
      rapid relapses and frequent readmissions. A statistical estimate of the risk of
      later heavy use based on 12 independent variables is presented.

PMID- 11827602
TI  - Aggression in the general Swedish population, measured with a new self-rating
      inventory: The Aggression Questionnaire--revised Swedish version (AQ-RSV).
AB  - The aim of the present study was to develop a Swedish self-rating instrument for
      clinical aggression research based on the American Aggression Questionnaire (AQ),
      which measures physical aggression, verbal aggression, anger, and hostility. To
      test this adapted Aggression Questionnaire--revised Swedish version (AQ-RSV), it
      was mailed to 781 randomly selected individuals, aged 20-40 year. A total of 497
      (64%) evaluable AQ-RSV inventories were obtained and analyzed statistically. Drop
      out analysis showed that non-responders were most often male and significantly
      older than responders. Among the responders, AQ-RSV showed significant sex
      differences in all aggression subscales except Hostility. Aggression was found to
      vary with age, geographical region, and size of home community. The AQ and the AQ
      RSV were comparable in correlations between the four aggression subscales and in
      alpha coefficients, which indicated considerable internal consistency.
      Development of the aggression-measuring instrument for Swedish conditions is
      important not only to study subtraits of aggression but to enable analyses of
      their relationships to neurobiological and psychiatric variables.

PMID- 11827603
TI  - Event recording in psychiatric care: development of an instrument and 1-year
      results.
AB  - Methods for regular monitoring of care and services are needed for psychiatrists
      to act on, to refine practice. We developed a computer-based instrument to be
      used by staff working with schizophrenic patients. The instrument was tested in a
      group of patients randomly assigned to an integrated-care program. Data on time,
      place, direct/indirect contacts, and the main elements of the content of care
      were regularly recorded on a pocket computer and later transferred to a desktop
      computer for analysis. One-year data on 24 subjects are presented on three
      levels: individual, case load, and total patient population. Of the encounters
      66% were individual patient contacts. Staff spent 59% of the time at patients'
      homes. A computer-aided system with built-in information on care delivery,
      program fidelity, and outcome can be the basis of decision-making on different
      health-management levels.

PMID- 11827604
TI  - What are the basic dimensions of movements? A psychometric evaluation of the
      Comprehensive Body Examination III.
AB  - The movements were examined in accordance with the Comprehensive Body
      Examination. The study objects were 99 persons: 17 pain syndrome patients (PSP
      group), 27 psychotic patients (PP group), 4 non-psychotic patients (NPP group),
      and a comparison group consisting of 51 students and staff members (SS group). On
      the basis of factor analysis three subscales were made: 1) Resistance to Passive
      Movements (RPM), with nine items, 2) Assistance to Passive Movements (APM), with
      six items, and 3) Motor Disturbances (MD), with three items. The internal
      consistency of the subscales was high (Chronbach's alpha, 0.81-0.96), and the
      intercorrelation low to moderate. The RPM subscale distinguished significantly
      between the SS group and both patient groups; the APM and MD subscales
      distinguished between the SS group and the PP group. The MD subscale also
      distinguished between patients taking drugs and those who did not, but there was
      no difference between patients without medication and the SS group.

PMID- 11827605
TI  - Schizophrenia in a patient with cerebral autosomally dominant arteriopathy with
      subcortical infarcts and leucoencephalopathy (CADASIL disease).
AB  - CADASIL is an autosomally dominantly inherited multi-infarct dementia caused by
      mutations in the Notch3 gene in chromosome 19. In this report we present the
      first patient in the world literature with CADASIL and schizophrenia and discuss
      the co-occurrence of these conditions in the light of the literature.

PMID- 11827606
TI  - Psychosocial functioning and psychiatric comorbidity among substance-abusing
      Icelandic adolescents.
AB  - Our objectives were to compare behaviour problem scores (BPS) for Icelandic
      adolescents admitted for detoxification treatment for alcohol and narcotic abuse
      as compared with the general population, in accordance with the Youth Self Report
      (YSR), and to describe psychosocial functioning and psychiatric comorbidity for
      the treated adolescents. The case series consisted of 103 adolescents, ages 12-18
      years, who completed the YSR at the end of a 10-day stay at the National Hospital
      of Addiction Medicine. The total BPS tallied from the YSR items was compared with
      scores for the general population. The psychiatric comorbidity and psychosocial
      functioning of the case series were assessed through diagnostic interviews in
      accordance with DSM-IV and ICD-10 criteria. The BPS for the 36 treated girls was
      significantly higher than for the general population (104 versus 36) and higher
      than for the 56 treated boys (82 versus 56) with 2 standard deviations above the
      norm for the population. Three-quarters of the adolescents had psychiatric
      comorbidity: conduct disorder (44%), depression (28%), or posttraumatic stress
      disorder (11%). The findings support the discriminative validity of the YSR as
      part of a structured global assessment of substance-abusing adolescents, in
      particular to identify the frequently present psychiatric comorbidities.

PMID- 11827607
TI  - Empirical weighting of the Standardized Mini Mental State Examination items among
      nursing home residents.
AB  - Missing items in the Mini Mental State examination are dealt with in different
      ways. The main aims of this study were to calculate a weighted item score for
      organic disorder on the basis of the item score of the Standardized Mini Mental
      State Examination (SMMSE) test regardless of the completeness of the test and to
      compare the criterion validity of the weighted scores with the ordinal scores for
      the SMMSE test. With a participation of 91%, the study included 100 nursing
      residents. All residents were tested with the SMMSE test and concurrently
      diagnosed in accordance with the ICD-10 by a consultant psychiatrist. The two
      assessments were mutually blinded. Multiple conditional forward logistic
      regression was used to select the items that most strongly predicted organic
      disorder as assessed by the psychiatrist. The weighted score had significantly
      better validity parameters, performed better on a receiver operating curve (ROC),
      and was better at dichotomizing the population into organic disorder than the
      commonly used ordinal score. We propose that missing items in the SMMSE should be
      scored as missing and included in empirical weighting on SMMSE items, which will
      then be substantially more valid than the SMMSE score itself.

PMID- 11827609
TI  - Injury proneness and personality.
AB  - The aim of this research was to investigate some personality factors among groups
      of 43 physically injured inpatients and 43 non-injured hospital-based controls.
      The participants completed the Eysenck Personality Questionnaire (EPQ) and the
      Coping Styles Questionnaire (CSQ). Logistic regression was used to compare the
      two groups on six psychological risk factors. The univariate regression models
      suggested three possible risk factors: extraversion, sensitization, and avoidance
      coping style. The multivariate regression model supported only extraversion and
      sensitization of emotion. Next, patients in the experimental group were
      questioned about whether they had considered preventive measures before the
      accident and whether they felt responsible for their injuries. Correlation
      analysis showed that introverted subjects felt more responsible for the sustained
      injuries than their extraverted counterparts. Sensitizers and subjects who scored
      high on psychoticism, neuroticism, and emotional coping had not considered
      preventive measures as often as others. Finally, the principal component analysis
      of risk factors was used to extract two correlates of injury-prone behaviour:
      extraversion and sensitized avoidance. It was concluded that psychological
      factors play an important role in predicting injury that is significant enough to
      require inpatient treatment. Two potential mechanisms of psychological impact
      have been suggested, notably distraction in extraverted subjects and
      overestimation in sensitizing avoiders.

PMID- 11827610
TI  - Personality disorders in parasuicide.
AB  - To examine the prevalence of personality disorders in a representative sample of
      patients admitted to inpatient care after a parasuicide, 64 consecutive patients
      were investigated with structured interviews for DSM-IV personality disorders and
      clinical interviews for Axis I disorders and suicidal behaviour. We found a
      borderline personality disorder (BPD) as principal diagnosis in 55% of the
      subjects and some other personality disorder (OPD) in an additional 23%. Multiple
      Axis II disorders were significantly more common in the BPD group, in which 71%
      met criteria for three or more personality disorders, compared with 7% in the OPD
      group. In the BPD group 20% did not have a concomitant Axis I disorder, whereas
      this was very uncommon in the other groups. A relatively large proportion (34%)
      in the BPD group used other parasuicide methods than drug intoxication, whereas
      in the other groups this was rare. The mean number of previous parasuicidal acts
      was significantly higher in the BPD group, in which 57% had three or more
      previous parasuicides, and a high proportion (60%) also had repeated a
      parasuicidal act within the last year. In the BPD group 69% had ongoing
      outpatient treatment. Only 25% of these outpatients had a borderline personality
      disorder reported in the hospital records, suggesting that the personality
      disorder might go undiagnosed. The study gives support to the importance of a
      focused and structured personality disorder diagnosis in customizing treatment
      for the person with a recent parasuicide.

PMID- 11827611
TI  - Autistic traits in obsessive-compulsive disorder.
AB  - In contrast to other non-psychotic psychiatric populations, subjects with
      obsessive-compulsive disorder (OCD) are more prone to have personality disorder
      from cluster A (the odd and eccentric cluster). The present study aims at further
      investigating the relationship between these and other personality traits in OCD
      subjects and their relation to high functioning autism (HFA) and Asperger
      disorder. Sixty-four subjects with OCD were included. Personality traits were
      assessed with the Karolinska Scales of Personality (KSP), and personality
      disorders with DSM-adapted questionnaires. In addition, autistic traits were
      assessed in 29 videotaped subjects, by 3 independent raters. Twenty percent of
      the subjects with OCD were identified as also having autistic traits. These
      subjects scored higher on KSP scales measuring muscular tension, psychasthenia,
      and inhibition of aggression and lower on socialization as compared with OCD
      subjects without autistic traits. Additionally, subjects with autistic traits
      fulfilled criteria for anxious personality disorders and paranoid personality
      disorders significantly more often than subjects without autistic traits. We
      propose that OCD is often related to HFA and Asperger disorder. Self-report
      questionnaires may be useful in establishing the diagnosis. However, those with
      the most obvious autistic features seem to be less able to identify these traits
      in themselves.

PMID- 11827612
TI  - Relationships between physical findings (GPE-78) and psychological profiles (MMPI
      2) in patients with long-lasting musculoskeletal pain.
AB  - The purpose of the study was to evaluate possible relationships between physical
      findings, as measured with the Global Physiotherapeutic Examination (GPE-78), and
      psychological characteristics, as measured with the revised Minnesota Multiphasic
      Personality Inventory (MMPI-2), in three groups of patients with long-lasting
      musculoskeletal pain. A total of 177 patients (114 women, 63 men), sick-listed
      owing to long-lasting musculoskeletal pain, were studied. The sample was
      subcategorized on the basis of pain localization, as marked on a pain drawing:
      group 1 = pain above a horizontal line in the thoracic-lumbar region (n = 24);
      group 2 = pain below the line (n = 48); group 3 = pain both above and below the
      line (n = 105). The GPE-78 consists of 78 standardized tests yielding
      quantitative information within five bodily domains: Posture, Movement, Muscle,
      Skin, and Respiration. Significant correlations were obtained between the GPE-78
      and the MMPI-2 with regard to somatization, somatic concern, and depression.
      Patients with localized pain (groups 1 and 2) had few correlations between bodily
      findings and psychological problems compared with many inpatients with
      generalized pain (group 3). Women showed correlations between the domains
      Posture, Movement, and Muscle and psychological problems, whereas men showed
      correlations with Movement, Skin and Respiration. A psychosomatic MMPI-2 "V
      profile" was present in groups 1 and 3. Women showed significantly higher scores
      than men. The relationships found between GPE-78 and MMPI-2 measures were
      significant, but findings differed depending on pain localization and sex.
      Patients with generalized pain had significantly more physical and psychological
      aberrations than patients with more localized pain.

PMID- 11827613
TI  - Course of depression: findings from cross-sectional survey in rural Udmurtia.
AB  - The aim of this study was to investigate the course of depression and to find the
      predictors of its chronicity and recurrence in the rural population of Udmurtia.
      In the sample of 232 respondents identified as having cases of unipolar
      depression, 21.1% had single episodes, 62.5% had recurrent episodes, and a
      chronic course was evident in 16.4%. Two demographic factors, Udmurt ethnicity
      and unmarried marital status, were significantly associated with both recurrent
      and chronic course of depression. A history of suicide attempt was associated
      only with recurrent depression; however, a trend towards a higher rate of suicide
      attempts was also found in the chronic depression subgroup. Factors associated
      only with chronic depression were poor family relationships and comorbidity with
      dysthymia.

PMID- 11827614
TI  - Depressive symptoms in middle-aged women are more strongly associated with
      physical health and social support than with socioeconomic factors.
AB  - The association of socioeconomic factors, health-related factors, and social
      support with depressive symptoms has been extensively studied. However, most
      epidemiological studies have focused on a few factors such as marital status,
      social class, and employment. In this study of middle-aged women we analyzed both
      univariate and multivariate associations of socioeconomic factors, perceived
      physical health factors, and social support with self-rated depressive symptoms
      measured with the Beck Depression Inventory. A nationwide sample (n = 1851) of
      Finnish women aged 48-50 years was analyzed. Socioeconomic, health-related, and
      social support factors were all measured with single items. All variables, except
      level of urbanization, were significantly associated with depressive symptoms in
      univariate analyses. Multivariate associations were examined with standard
      multiple regression analyses in three stages: first with the socioeconomic
      factors, then with socioeconomic and health factors, and finally entering the
      social support factors into the regression model. In the first model, being
      either on a sick leave or at home as working status, being divorced, and having
      low income reached significance. In the second model, being divorced and having
      poor perceived physical health were the most powerful among the five significant
      variables. In the last model, explaining 32% of the variance, the most powerful
      predictors of depressive symptoms were perceived current physical health,
      satisfaction with received social support, and quality of intimate relationships.
      For the prevention or intervention of depressive symptoms among middle-aged women
      in the population subjects with concurrent subjective or objective health
      problems and poor social support seem to comprise a particularly important target
      group.

PMID- 11827615
TI  - Ganser syndrome after solitary confinement in prison: a short review and a case
      report.
AB  - A short review of the Ganser syndrome is given. The condition is a rare, probably
      dissociative, disorder with transient Vorbeireden as the central symptom. The
      case of a middle-aged man developing a transient Ganser syndrome after long-term
      solitary confinement in a remand prison is presented. Systematic investigation of
      268 remand prisoners confirms the rarity of the syndrome, as only the case
      subject had this disorder.

PMID- 11827616
TI  - The relation of parental practices and self-conceptions to young adolescent
      problem behaviors and substance use.
AB  - The object of the present research was to examine the role of parenting practices
      for young adolescent psychosocial adjustment and self-regulation problems. The
      sample included 287 sixth- and seventh-grade subjects from intact families. The
      participants completed a questionnaire that measured variables including family
      interaction, parental involvement in children's activities, parental support,
      joint decision-making, and monitoring of children's behavior. Children's
      involvement with friends, after-school activities, school achievement, and self
      reported externalizing behaviors (problem behaviors, cigarette and alcohol use)
      were also measured. Self-concept domains (scholastic competence, social
      acceptance, and behavioral conduct) were assessed with Harter's Self-Perception
      Profile. The findings indicated that self-conceptions of positive behavioral
      conduct and higher parental monitoring of children's activities were consistently
      negatively related to young girls' and boys' behavior problems and substance use.
      Parental monitoring was higher for girls and for younger children. Lower
      monitoring was also related to children's pattern of after-school activities that
      were connected to at-risk behavior. Parental involvement and supervision of
      children's day-to-day activities seem particularly important in socializing
      children's behavior at the time of early adolescence.

PMID- 11827617
TI  - Memory enhancement training for older adults with mild cognitive impairment: a
      preliminary study.
AB  - 'Mild cognitive impairment' (MCI) in older adults refers to a significant decline
      in memory function but not other cognitive functions. Pharmacological and non
      pharmacological treatments for MCI are needed. The present randomized clinical
      trial tests the efficacy of a cognitive and behavioral treatment to improve
      memory performance and participants' attitudes about their memory. A multi
      faceted intervention that included education about memory loss, relaxation
      training, memory skills training, and cognitive restructuring for memory-related
      beliefs was compared to a no-treatment control condition. Outcomes included
      memory performance and appraisals of memory function and control. Results
      indicate that the treated group had significantly better memory appraisals than
      controls at the end of treatment and at a six-month follow-up. There were no
      differences between groups on memory performance at post-test but at follow-up
      the trained individuals showed a trend toward better word list recall than
      controls. Findings suggest that individuals with MCI can benefit from multi
      component memory enhancement training. Further development of such training
      programs and tests of their efficacy alone and in combination with medications
      are needed.

PMID- 11827618
TI  - Dissociation between performance on abstract tests of executive function and
      problem solving in real-life-type situations in normal aging.
AB  - This study examined the effects of normal aging on real-life-type problem-solving
      performance, using problems that had previously been found to be sensitive to
      lesions involving the frontal lobes. Executive skills assessed on abstract
      neuropsychological tests tend to decrease with normal aging. The effects of aging
      on tasks reliant on everyday knowledge and experience are less well understood.
      In the present study, groups of healthy older and younger people were compared on
      ability to solve real-life-type problems covering a range of everyday
      interpersonal situations. Performance was also examined on a range of
      standardized neuropsychological tests involving executive skills. Older people
      were similar to younger people in most aspects of everyday problem-solving
      performance, although the older group appeared to use a different strategy to the
      younger group in generating potential problem solutions. Both groups performed
      normally for their age on the executive tests. Comparisons based on raw scores
      rather than age-adjusted scores showed the younger group to perform better on the
      executive tests, but not on the problem-solving task. The possible contribution
      of knowledge and experience to problem solving on the current task is discussed.
      The greater life experience of the older group is likely to be the biggest
      contributory factor in maintaining problem-solving performance.

PMID- 11827619
TI  - Health literacy and performance on the Mini-Mental State Examination.
AB  - The objectives of the study were to determine the relationship between functional
      health literacy and performance on the Mini-Mental State Examination (MMSE). New
      Medicare managed-care enrollees aged 65 years and older, living independently in
      the community in four US cities (Cleveland, Houston, Tampa, and Fort
      Lauderdale/Miami), were eligible to participate. In-home interviews were
      conducted to determine demographics and health status, and interviewers then
      administered the Short Test of Functional Health Literacy in Adults (S-TOFHLA)
      and the MMSE. We then determined the relationship between functional health
      literacy and the MMSE, including total scores, subscale scores (orientation to
      time, orientation to place, registration, attention and calculation, recall,
      language, and visual construction), and individual items. Functional health
      literacy was linearly related to the total MMSE score across the entire range of
      S-TOFHLA scores (R(2) = 0.39, p < 0.001). This relationship between health
      literacy and MMSE was consistent across all MMSE subscales and individual items.
      Adjustment for chronic conditions and self-reported overall health did not change
      the relationship between health literacy and MMSE score. Health literacy was
      related to MMSE performance even for subscales of the MMSE that were not
      postulated to be directly dependent on reading ability or education (e.g. delayed
      recall). These results suggest that the lower MMSE scores for patients with low
      health literacy are only partly due to 'test bias' and also result from true
      differences in cognitive functioning. 'Adjusting' MMSE scores for an individual's
      functional health literacy may be inappropriate because it may mask true
      differences in cognitive functioning.

PMID- 11827620
TI  - The experience of caring for older people with dementia in a rural area: using
      services.
AB  - This paper reports findings from the carer component of the Gwynedd Dementia
      Study. It is based on carer interviews, using quantitative and qualitative data.
      It confirms earlier findings that carers for people with dementia are typically
      female and older than other carers, although it notes that caring husbands are
      amongst the oldest carers. The problems that are most common are those that cause
      psychological stress to carers. Carers were found to receive both help and
      appreciation from their families and to perceive neighbours to be helpful if
      needed. In Gwynedd, as elsewhere, levels of formal service inputs are low, but
      most of the carers appeared to receive the services they needed. Problems are
      primarily associated with crisis support and long-term care is accepted
      reluctantly. It is suggested that community care dementia specialists could play
      a supporting role for carers.

PMID- 11827621
TI  - Patterns of outcome of caregiving for the impaired elderly: a longitudinal study
      in rural Japan.
AB  - This longitudinal study investigates the experiences among Japanese caregivers
      who provide informal care at home to the impaired elderly over one year. Little
      is known about longitudinal changes in caregivers' burden in Japan. Between 1998
      1999, 47 pairs of impaired elderly and their caregivers were followed in
      Matsuyama Town in a rural area of northern Japan. Caregivers were interviewed
      initially and then again 12 months later. Findings indicated that the mean score
      of the Zarit Burden Interview at Time 2 was significantly lower than that of Time
      1, suggesting that caregivers adapted to their role over time. Outcomes were
      further categorized as successful and unsuccessful, depending on the pattern of
      change over one year. Two factors were related to the outcome in univariate
      analyses: caring for someone with dementia, and caregiver being a spouse.
      Logistic regression demonstrated that caring for someone with dementia was five
      times more likely to be associated with an unsuccessful outcome. The caregiver
      spouse was five times more likely to be associated with a successful outcome,
      while daughters-in-law were more likely to have an unsuccessful outcome. The
      present study suggests that (1) changes in well-being among caregivers in Japan
      are similar to those observed in most studies in the West, and (2) there was
      evidence of both the adaptation and wear-and-tear models among caregivers over
      time.

PMID- 11827622
TI  - Abstinence versus alcohol use among elderly rural Baptists: a test of reference
      group theory and health outcomes.
AB  - Reference groups, such as religious groups, are thought to provide individuals
      with normative frameworks which set and maintain standards for them. Persons who
      belong to a reference group, yet do not comply with the standards of that group,
      i.e. non-conformists, are thought to experience cognitive dissonance which in
      turn may lead to psychological discomfort and adverse physical health outcomes.
      In a community-based, racially mixed sample of elderly Baptists in the rural
      south of the United States (n = 1155), where Baptist churches proscribe alcohol
      use, we studied whether alcohol use was associated with adverse physical and
      mental health assessments. No relationship was found between non-conformist
      behavior among rural Baptists and adverse health outcomes for either Whites or
      African-Americans in controlled analyses. More frequent church attendance among
      African-American Baptists, but not for White Baptists, was strongly associated
      with abstinence from alcohol.

PMID- 11827623
TI  - Employed family caregivers of cognitively impaired elderly: an examination of
      role strain and depressive symptoms.
AB  - This paper compares employed and non-employed caregivers of cognitively impaired
      elderly family members. Using two competing positions derived from role theory,
      role conflict and role expansion, we explored whether holding the positions of
      both caregiver and worker led to greater role overload and psychological role
      conflict, or provided an outlet that helps caregivers better manage the demands
      placed on them. We found no differences between employed and non-employed
      caregivers on measures of role overload, worry and strain, and depression. For
      working caregivers, however, greater conflict on the job was associated with
      higher role overload and worry and strain while beneficial work experiences were
      only weakly associated with lower role overload and worry and strain. There was
      an interaction effect between positive work experiences and role overload when
      predicting depressive symptoms. These results provide some support for role
      conflict, but also suggest that caregivers may vary considerably in how they
      adapt to multiple roles.

PMID- 11827624
TI  - Association of life events and psychological distress in family caregivers of
      dementia patients.
AB  - Relationships between life events and psychological distress were investigated
      for 197 dementia caregivers and 218 non-caregivers. Participants indicated which
      events on the Louisville Older Persons Events Scale they had experienced over the
      past six months. Life events were then classified as associated or unassociated
      with care-giving using differences in incidence rates between caregivers and non
      caregivers. Primary care-giving stressors and associated life events were most
      predictive of psychological distress among caregivers. Among non-caregivers,
      unassociated negative life events were the strongest predictors of depression and
      life satisfaction. Implications for the assessment of life events and caregiver
      interventions are discussed.

PMID- 11827625
TI  - Reported practices of primary care physicians in the diagnosis and management of
      dementia.
AB  - The shortage of geriatric specialists in the US may require that primary care
      physicians (PCPs) receive more education on diagnosing and managing dementia
      since the number of older Americans with dementia will increase from about five
      million in 2010 to up to 14 million in 2050. Thus, we administered a brief,
      anonymous questionnaire to determine PCPs' diagnostic, referral, and management
      practices to a convenience sample of 142 PCPs in Arkansas. We reworded a Scottish
      survey to conform to terminology used in the US and added items on referral
      practices. The PCPs who reported difficulty establishing the diagnosis of
      dementia had more difficulty telling the diagnosis (O.R = 3.59, p < 0.004). The
      PCPs were less likely (p < 0.001) to tell the patient if they suspected dementia
      (73%) than if they were sure the patient had dementia (88%). In both cases, they
      were more likely to tell the family (92% & 100%, respectively), although this
      difference was not statistically significant. The PCPs discussed disease
      progression and driving risks with patients and families, but few referred them
      to social workers or community agencies. Findings support training PCPs in the
      diagnosis and management of persons with dementia and providing tools to improve
      care.

PMID- 11827626
TI  - Using simulated presence therapy with people with dementia.
AB  - Simulated Presence Therapy (SPT) is a relatively new intervention, which has been
      reported to reduce levels of anxiety and challenging behaviour amongst people
      with dementia. The intervention consists of playing a tape of their carer's voice
      to a person with dementia over a personal stereo. This study provides details of
      the effectiveness of SPT with four in-patients on an assessment ward. The four
      showed differing levels of response to the SPT tapes. It is suggested that the
      differing response of participants may be related to their differing attachment
      styles.

PMID- 11827627
TI  - Social interaction associated with visual art discussions: a controlled
      intervention study.
AB  - The investigation was aimed to assess the link between visual art discussions and
      social interaction. The study was designed as a controlled intervention study.
      Participants were older women living in a block of specially designed older
      persons' flats in Sweden. Reproductions of well-known artists' works of art were
      used as an intervention instrument. Measurements were older women's self-reported
      social interaction. The results show significant improvement in the visual art
      group compared to the matched control group. The differences in ratings between
      the groups indicated increased social interaction in the visual art group, which
      continued to exist four months after the intervention. Visual art discussions
      encouraged reminiscence and stimulated the older women to be more socially
      active. The study is an example of how visual art could be used in order to
      stimulate older women to interact in a social network in order to remain in
      contact with the world instead of retreating from it.

PMID- 11827628
TI  - Analgesics in the elderly.
AB  - The aim of the study is to investigate whether elderly patients on long-term weak
      opioid analgesics could suffer the problems of tolerance and dependence. The
      prevalence of potential dependence amongst long-term users was assessed by a semi
      structured questionnaire applying the Diagnostic Criteria for Research (DCR-10)
      criteria for Dependence Syndrome. The sample consisted of 25 randomly selected
      elderly patients drawn from four practices in North Cheshire, who had been on
      continuous repeat prescription of low potency opioid and compound analgesics
      containing them for a minimum of one year without apparent problem to themselves
      or their GPs. Approximately 2.8% of the elderly GP practice population were shown
      to be on opioid analgesics continuously for at a least one year. The study found
      that an estimated 40% of patients on low potency opioids fulfilled the DCR-10
      criteria for Dependence Syndrome. It could be argued however that the finding may
      be, at least partly, the result of an undetermined specificity of DCR-10 as a
      screening tool. The finding, in such a small sample, is interesting but requires
      critical examination, as we believe it to be the first study of the possible
      effect of long-term use of opioid analgesics in primary care. The unexpectedly
      high prevalence highlights the need for further research in this area.

PMID- 11827629
TI  - Thoughts on current guidelines for managing patients with acute coronary
      syndromes.

PMID- 11827630
TI  - Recent clinical trials in valvular heart diseases.

PMID- 11827631
TI  - The renin-angiotensin system in mitral regurgitation: a typical example of tissue
      activation.
AB  - Mitral regurgitation (MR) creates a unique hemodynamic stress by inducing a low
      pressure form of volume overload due to ejection into the left atrium, without
      the pressure component that accompanies aortic regurgitation. Chronic therapy
      with vasodilators has been shown to reduce left ventricular wall stress, and
      thereby delay or obviate the need for valve replacement in aortic regurgitation;
      however, no data are currently available in patients with chronic MR using
      standard vasodilators or agents that block renin-angiotensin system (RAS)
      components. Studies in a clinically relevant dog model of experimentally induced
      MR demonstrate upregulation of the cardiac RAS. However, RAS blockade fails to
      improve left ventricular remodeling and function, whereas beta-adrenergic
      blockade results in restoration of left ventricular chamber and myocyte function.

PMID- 11827632
TI  - The long-term outcome of mitral valve repair for mitral valve prolapse.
AB  - The rationale of early surgery for severe chronic mitral regurgitation (MR) due
      to mitral valve prolapse (MVP) has been developed over the past decade on the
      basis of the understanding of the natural history of this disease and the
      predictors of outcomes after surgical correction of MR. The important decrease in
      operative mortality associated with the advancements in myocardial preservation,
      and more importantly the improved reparability of the myxomatous mitral valve,
      were an additional incentive to develop the concept of early surgery. Previous
      studies showed that mitral valve repair offers a survival advantage at short- and
      10-year follow-up, and therefore suggested that it should be the treatment of
      choice for severe MR due to MVP. Moreover, very recent data provided new insight
      on the very long-term follow up, ie, beyond the usual first 10 years in which the
      initial survival benefit of repair may be negated by a late deterioration.

PMID- 11827633
TI  - Aortic valve sclerosis as a marker of active atherosclerosis.
AB  - Aortic sclerosis is a calcific disease of the aortic valvular leaflets defined as
      focal leaflet thickening without significant obstruction to left ventricular
      outflow. Several clinical factors are associated with calcific aortic valve
      disease, including male sex, smoking, hypertension, age, hypercholesterolemia,
      and diabetes. Histologic and biochemical studies suggest similarities between the
      mechanisms involved in the development of aortic sclerosis and atherosclerosis,
      suggesting these two diseases may share common pathophysiologic mechanisms. In a
      recent prospective trial, the presence of aortic sclerosis was associated with an
      approximately 50% increase in cardiovascular mortality and myocardial infarction,
      even after correction for age, gender, known coronary artery disease, and
      clinical factors associated with a aortic sclerosis.

PMID- 11827634
TI  - The long-term outcome of balloon valvuloplasty for mitral stenosis.
AB  - Percutaneous mitral commissurotomy (PMC) is the treatment of choice in young
      patients who have favorable valve anatomy. It affords an event-free survival
      greater than 90% at 5 to 7 years,. Economic considerations are the main
      limitation of PMC in such patients, who are mainly encountered in developing
      countries. Mitral stenosis in older patients with less favorable valve anatomy is
      the most frequent presentation in Western countries. This represents a
      heterogeneous group, but predictive analyses are helpful in deciding who should
      have PMC. The main conclusion is that the prediction of immediate and late
      results is multifactorial. Good results can be expected in young patients with
      unfavorable valve anatomy who do not have a very tight stenosis, are moderately
      symptomatic, and in sinus rhythm. In addition, PMC may reduce the thromboembolic
      risk related to mitral stenosis.

PMID- 11827635
TI  - Mechanistic insights into functional mitral regurgitation.
AB  - Effective valve repair in patients with mitral regurgitation (MR) demands an
      understanding of its mechanism. In patients with ischemic heart disease and
      functional MR, which doubles late mortality, normal leaflets are apically
      displaced. This reflects an altered balance of forces acting on the leaflets:
      increased tethering forces restricting closure, resulting from an altered
      geometry of leaflet attachments, and decreased ventricular forces acting to close
      the leaflets. Extensive evidence confirms a central and predominant role of
      tethering as the final common pathway inducing functional MR; left ventricular
      (LV) pressure dynamically modulates the orifice area. Because ischemic MR is a
      disease of the entire mitral complex, including the remodeling LV, reducing
      annular size alone is often ineffective. Undersizing rings attempts to compensate
      for tethering; new and potentially more effective strategies directly address
      tethering by infarct plication, papillary muscle repositioning with a localized
      patch, or basal chordal cutting to increase coaptational surface area without
      prolapse. A comprehensive understanding of the valve in its ventricular context,
      therefore, provides new opportunities for successful valve repair in patients.

PMID- 11827637
TI  - Innovative strategies in the management of acute stroke.
AB  - Advances in acute stroke therapy are rapidly changing our approach to management
      of patients with ischemic stroke. Intravenous tissue-plasminogen activator (tPA)
      was the first treatment demonstrated in a randomized controlled trial to improve
      outcome if given within the first 3 hours of stroke onset. Subsequent trials
      failed to extend the time window for intravenous therapy beyond 3 hours. Intra
      arterial thrombolysis provides an alternative approach, with several advantages
      over intravenous therapy. The major drawback is the additional time needed for
      the interventional procedure, and the equipment and personnel requirements. New
      strategies aimed at reducing the total time from stroke onset to recanalization
      of occluded arteries include a combined intravenous/ intra-arterial delivery of
      thrombolysis and mechanical devices. For the millions of stroke survivors,
      investigations are now underway into the possibility of improvement of function
      through neuronal transplantation.

PMID- 11827639
TI  - Evaluation and management of acute ischemic stroke.
AB  - Stroke continues to be a major cause of adult mortality and disability. After
      numerous clinical trials and hundreds of millions of dollars spent on research,
      only two drugs are effective in treating patients with acute stroke. Recombinant
      tissue-plasminogen activator improves the chance of an excellent outcome in
      treated patients by 30%. Danaparoid sodium improves the chance of a very
      favorable outcome in treated patients with stroke due to large artery
      atherosclerosis. Although acute treatments are limited, our understanding of
      stroke pathogenesis and the importance of preventing poststroke complications has
      improved patient outcome significantly.

PMID- 11827638
TI  - Mechanisms of cardioembolic stroke.
AB  - Cardiac embolism is often involved as a mechanism for embolic stroke, and may be
      implicated in many strokes that have traditionally been considered of unknown
      origin (cryptogenic strokes). In recent years, significant advancements have been
      made in understanding and reducing the risk of stroke from long-known
      cardioembolic sources (atrial fibrillation, intracardiac thrombus or tumor,
      infective endocarditis). Also, improved cardiac imaging, especially
      transesophageal echocardiography, has allowed the identification of newer embolic
      sources of stroke (aortic atheromas, patent foramen ovale, atrial septal
      aneurysm). This article reviews the current understanding of cardiac embolism as
      a mechanism for stroke, and the preventive options that are currently adopted to
      decrease the stroke risk.

PMID- 11827640
TI  - Management of hemorrhagic stroke.
AB  - Fifty thousand Americans suffer an intracerebral hemorrhage (ICH) annually, one
      third of whom die as a result. Poorly controlled hypertension is the most
      important risk factor for ICH. Over time it results in pathologic changes to
      small intracranial vessels, leading to their rupture. All stroke patients,
      including those with suspected ICH, require emergent evaluation. Surgical
      intervention is appropriate for some ICH patients, although intensive medical
      management of intracranial pressure and the systemic consequences of ICH can
      reduce morbidity in all. Innovative medical and surgical therapeutic approaches
      hold promise for improved treatment in the future, but prevention is the key for
      reducing morbidity in the short term.

PMID- 11827641
TI  - Prevention of ischemic stroke.
AB  - The primary risk factors for stroke are known, and attention to primary care of
      these disorders should reduce the incidence of stroke significantly. Control of
      hypertension, diabetes, and hyperlipidemia have all been shown to reduce the rate
      of stroke. Identification of potential cardioembolic sources of stroke,
      particularly atrial fibrillation, can prevent stroke with appropriate application
      of anticoagulation. Duplex Doppler B-mode sonography can establish the extent of
      carotid artery disease in patients with cervical bruit or risk factors for
      atherosclerosis, and indicate which conditions should be managed medically or
      surgically. Patients with a history suggestive of transient ischemic attacks can
      also be screened noninvasively with duplex sonography to determine if they have a
      critical carotid stenosis and require carotid endarterectomy. New advances in
      platelet antiaggregant therapy with ticlopidine, clopidegril, and the combination
      of aspirin with dipyridamole have also reduced the rate of stroke to a greater
      degree than standard treatment with aspirin. The incidence of this devastating
      illness could possibly be reduced by 50% with attentive primary care management.
      The cardiologist is often involved in the treatment of patients at risk for
      stroke, and is in an ideal position to provide this care.

PMID- 11827642
TI  - Sleep-disordered Breathing in Neuromuscular Disease.
AB  - Patients with neuromuscular disorders involving respiratory muscles (upper airway
      muscles, respiratory accessory muscles, diaphragm, even abdominal muscles that
      stabilize the chest) have more significant problems with breathing during sleep,
      especially during REM sleep, than during wakefulness. There are means of
      appropriately treating sleep disordered breathing and improving the quality of
      life of these patients. Treatment helps to avoid daytime symptoms and additional
      autonomic nervous system dysfunction. The treatment involves support of breathing
      during sleep. It must be adjusted to the severity of the problem during sleep,
      which implies systematic investigation and treatment based on polygraphic
      recordings during sleep. Patients, even when stable, need to be monitored during
      sleep at least once a year and more often if symptomatic, ie, appearance of any
      daytime symptom or frequent upper respiratory infection or indication of daytime
      CO(2) retention.

PMID- 11827643
TI  - Rapid Eye Movement Sleep-related Parasomnias.
AB  - Among the rapid eye movement (REM) sleep-related parasomnias, the most common and
      important disorder for which patients present is REM sleep behavior disorder
      (RBD). Rapid eye movement sleep behavior disorder is often undiagnosed for many
      years, despite the sometimes bizarre and harmful behaviors involved. Complete
      evaluation and accurate diagnosis are essential for proper management. This
      includes medical, sleep/wake, psychiatric, and neurologic histories. Although
      they may raise feelings of guilt or shame, questions related to sexual and
      violent behaviors should be directed towards the identified patient as well as
      their bed partners. Objective studies should include nocturnal polysomnogram with
      audiovisual monitoring of behavior, electromyography (EMG) of all limbs, and
      seizure montage. Brain imaging, clinical electroencephalogram (EEG),
      neuropsychometric testing, and actigraphy may be used adjunctively. Clinicians
      should have a high index of suspicion for other neurologic conditions, especially
      neurodegenerative disorders and narcolepsy, because many patients with RBD have
      these conditions. Rapid eye movement sleep behavior disorder may actually precede
      symptoms and signs associated with other neurologic disorders, so close follow-up
      is recommended. Medications that may be causing or exacerbating RBD should be
      withdrawn, if possible. Clonazepam is very effective in reducing the symptoms of
      RBD. This treatment is generally well tolerated and may be used long-term.
      Discontinuation of clonazepam usually leads to relapse of symptoms. Safety
      related issues should be discussed with patients and their families.

PMID- 11827644
TI  - Sleep-related Headache.
AB  - The relationship between sleep and headache has great individual variation.
      Headaches that arise primarily out of sleep have a broader differential diagnosis
      than random headaches, and a specific cause should be identified, if possible.
      Sleep apnea can trigger or cause sleep-related headaches. Hypnic headache is one
      of a few specific, uncommon, idiopathic sleep-related headache syndromes.
      Treatment of sleep-related headache includes treating the underlying cause, such
      as sleep apnea, and prescribing medications usually used for headache as well as
      medications for sleep disorders.

PMID- 11827645
TI  - Sleep and Epilepsy.
AB  - Seizures and antiepileptic drugs (AEDs) affect sleep macroarchitecture and may
      produce excessive daytime sleepiness (EDS) in patients with epilepsy. Sleep is a
      potent activator of seizures and epileptiform discharges. In some patients,
      seizures occur exclusively or predominately in sleep. Benign focal epilepsy of
      childhood with centrotemporal spikes (BECTS), supplementary sensorimotor area
      epilepsy (SSMA) and Lennox Gastaut syndrome are a few of the more common epilepsy
      syndromes characterized by nocturnal seizures. Excessive daytime sleepiness is a
      common complaint of patients with epilepsy. Causes of EDS include seizures, AEDs,
      poor sleep hygiene, and coexisting sleep disorders. Pharmacologic therapy is
      aimed at identifying the single most effective drug for a given seizure type or
      epilepsy syndrome. Polytherapy is associated with a higher likelihood of adverse
      effects--most notably, EDS. Poor sleep hygiene leads to sleep fragmentation that
      can exacerbate seizures and EDS. Primary sleep disorders should be suspected in
      patients with EDS, particularly those treated with monotherapy at low serum drug
      concentrations and well controlled seizures. Treatment of sleep disorders may
      lead to better seizure control.

PMID- 11827646
TI  - Central Nervous System Germ Cell Tumors.
AB  - Germ cells tumors most commonly affect children and adolescents, and occasionally
      arise in the central nervous system. Except for mature teratomas, they are all
      malignant. Pure germinomas are exquisitely sensitive to treatment and are highly
      curable with craniospinal radiation therapy. Surgery plays no role other than to
      establish the histologic diagnosis. Diagnostic confirmation includes normal
      levels of serum and cerebrospinal fluid alpha-fetoprotein and at most only minor
      elevations in beta human chorionic gonadotrophin (beta-hCG). Although it has
      become quite common to use chemotherapy to reduce the dose and field of radiation
      in the treatment of germinomas, longer follow-up in these patients is revealing a
      significant number of subarachnoid and ventricular recurrences. A recent follow
      up study in patients treated for intracranial germinomas showed no significant
      difference in the psychosocial functioning of those treated with chemotherapy and
      radiation compared with those treated with chemotherapy alone, which raises
      further questions about the rationale for modifying a proven successful
      treatment. Malignant non-germinomatous germ cell tumors are much more resistant
      to treatment and difficult to cure. Surgical resection appears to have prognostic
      significance, although the predilection for midline structures makes complete
      resection difficult if not impossible at times. The best results have been
      obtained with platinum-based chemotherapy and full-dose craniospinal radiation
      therapy. Pure teratomas are not typically responsive to chemotherapy or radiation
      therapy and surgery is the only proven treatment modality.

PMID- 11827647
TI  - Leptomeningeal Neoplasms.
AB  - Leptomeningeal metastases are a late, devastating complication of systemic cancer
      that typically occurs in conjunction with other systemic relapse. The most common
      neurologic symptoms include headache, altered mentation, and difficult walking.
      Diagnosis is established by neuroimaging and cerebrospinal fluid analysis. The
      prognosis is poor with a median survival of 6 to 8 weeks; therefore most
      treatment interventions are palliative. Radiotherapy should be given to sites of
      bulky or symptomatic tumor. Intrathecal chemotherapy is most effective in
      patients with lymphoma, leukemia, and breast cancer. Systemic chemotherapy may be
      more effective in treating bulky leptomeningeal tumor. Ventriculoperitoneal
      shunting can be extremely useful in patients with obstructive hydrocephalus or
      increased intracranial pressure.

PMID- 11827648
TI  - Acoustic Neuromas.
AB  - Patients with acoustic neuromas have several treatment options that include
      observation, surgical resection, stereotactic radiosurgery, and fractionated
      radiotherapy. Resection is indicated for patients with larger tumors that have
      caused major neurologic deficits from brain compression. Surgeons perform
      stereotactic radiosurgery as the main alternative to acoustic tumor resection
      with the goals of preserved neurologic function and prevention of tumor growth.
      The long-term outcomes of radiosurgery, particularly with gamma knife technique,
      have proven its role in the primary or adjuvant management of this disease.
      Radiotherapy can be offered to selected patients with larger tumors in whom
      radiosurgery may not be feasible. Patients with neurofibromatosis type-2 pose
      specific challenges, particularly in regard to preservation of hearing and other
      cranial nerve function. The primary clinical issues include avoiding tumor
      related or treatment-related mortality, prevention of further tumor-related
      neurologic disability, minimizing treatment risks such as spinal fluid leakage,
      infections, or cardiopulmonary complications, maintaining regional cranial nerve
      function (facial, trigeminal, cochlear, and glossopharyngeal/vagal), avoiding
      hydrocephalus, maintaining quality of life and employment, and reducing cost. All
      treatment choices should strive to meet all of these goals.

PMID- 11827649
TI  - Chordoma.
AB  - Optimal therapy of chordoma is a combined approach of surgical resection followed
      by proton beam irradiation for residual disease. The goals of surgery are to
      establish a definitive diagnosis, obtain total or maximal resection, and "shape"
      any residual disease so that it is favorable for radiation. Given the difficult
      locations and large sizes of these tumors, potential morbidity from these
      surgeries is high. Chordomas respond best to high doses of radiation, but nearby
      neurologic structures limit doses that can be delivered. Proton beam radiation
      appears to have a distinct advantage over conventional external beam radiation in
      this disease because of the rapid fall-off of radiation beyond the target.
      Unfortunately, the data on efficacy and safety of treatments for chordoma is
      limited because of the rarity of disease. Current reports in the literature are
      exclusively case series and reports, limiting the strength of the conclusions
      that can be drawn.

PMID- 11827650
TI  - [Interest in the study of genetic variants of the promoter region of the UGT1A1
      gene in neonatal jaundice].
AB  - BACKGROUND: A relationship between polymorphism in the promoter region of the
      UGT1A1 gene (associated with Gilbert's syndrome) and the development of jaundice
      has recently been demonstrated. This polymorphism is due to (TA)7 instead of wild
      type (TA)6. OBJECTIVE: To investigate the relationship between Gilbert's syndrome
      and neonatal jaundice by evaluating the distribution of (TA)7 in a population of
      newborns. METHODS: A total of 136 newborns were studied: 21 had neonatal
      jaundice, 69 were healthy and the remaining newborns had various diseases. DNA
      from each patient was used to amplify, by polymerase chain reaction, the promoter
      region of the UGT1A1 gene, which flanks the TATA box where the polymorphism is
      located. RESULTS: In the group without jaundice, 53 % of the newborns were normal
      (6/6 genotype), 40 % were 6/7 and 7 % were 7/7. In the group with jaundice, 33 %
      of the newborns were normal, 53 % were heterozygous (6/7) and 14 % were
      homozygous (7/7). Comparison of the groups revealed that the prevalence of UGTA1A
      polymorphism tended to be greater among jaundiced newborns (p 0.09). CONCLUSION:
      The results of this study suggest that there is a relationship between neonatal
      jaundice and Gilbert's syndrome among the Spanish population. These results,
      together with those of other authors, suggest that genetic screening for
      Gilbert's syndrome should be included in the investigation of neonatal jaundice
      in our population. Further studies with a greater number of subjects would
      determine the exact relationship between marked neonatal jaundice and IGTA1A
      polymorphism. Key words:

PMID- 11827651
TI  - [Factors associated with discontinuance of breastfeeding].
AB  - OBJECTIVES: To determine possible factors that may influence the decision to stop
      breastfeeding. METHODS: We carried out a prospective study of 545 women who had
      given birth in the public hospitals of Gran Canaria. The study encompassed a 6
      month postnatal lactation period. The chi-squared test was used to test the
      hypothesis of an association between variables. Odd-ratios were calculated for
      factors significantly associated with breastfeeding and were adjusted for the
      remaining factors using the logit method. RESULTS: Mothers were more likely to
      continue breastfeeding if they had made the decision to breastfeed before giving
      birth, had received information from health personnel during pregnancy, if they
      were older, if they were university graduates, if a short time had elapsed
      between giving birth and starting breast-feeding, if they had not given the baby
      a bottle in the first days after birth and if the birth had been normal without
      complications. The decision to stop breastfeeding was usually taken by the mother
      herself and was related to lactation problems (shortage of milk, the baby's
      hunger) and to personal difficulties. CONCLUSIONS: Once breastfeeding has begun,
      prenatal care factors as well as hospital practices strongly influence its
      continuation. Bottle feeding in the hospital is negatively associated with
      breastfeeding at 15 days and at 3 and 6 months. Socioeconomic and cultural
      factors as well as age are also determining factors. Personal reasons for
      discontinuing breast-feeding, such as the demands of work, become more frequent
      over time.

PMID- 11827652
TI  - [Regurgitation and gastroesophageal reflux disease, cyclic vomiting syndrome and
      recurrent or chronic vomiting of other etiology].

PMID- 11827655
TI  - [Macrophage activation syndrome: a diagnostic challenge].
AB  - Macrophage activation syndrome, or hemophagocytic syndrome, is a rare disease
      with high morbidity and mortality. It is a disorder of the mononuclear phagocyte
      system. Two forms have been described; primary or familial hemophagocytic
      lymphohistiocytosis and secondary or sporadic hemophagocytic syndrome. Diagnosis
      of macrophage activation syndrome poses a real challenge for the pediatrician and
      in many cases is only made at autopsy. We describe two patients with
      hemophagocytic syndrome associated with parvovirus B19 and Epstein-Barr virus
      infection.

PMID- 11827656
TI  - [Difficulties in the diagnosis of familial hemophagocytic lymphohistiocytosis].
AB  - Familial hemophagocytic lymphohistiocytosis (FHL) is characterized by
      proliferation and non-malignant activation of histiocytes and T lymphocytes in
      the reticuloendothelial system. Diagnostic guidelines include fever,
      splenomegaly, cytopenia, hypertriglyceridemia and/or hypofibrinogenemia with
      hemophagocytosis in the bone marrow, spleen or lymph nodes. In many patients
      diagnosis is difficult due to the lack of diagnostic criteria, hemophagocytosis,
      variability of clinical presentation, spontaneous improvement and the absence of
      a specific marker of the disease. When there is strong clinical suspicion of FHL,
      chemotherapy and immunosuppressor treatment should be started early to achieve
      complete cure and should be followed by hematopoietic stem cell transplantation.
      We present the case of a 2-month-old girl who presented fever, anemia and
      thrombocytopenia, enlarged liver and spleen, hyperferritinemia,
      hypertriglyceridemia, and hypertransaminasemia without the finding of
      hemophagocytosis in bone marrow. Two of the girl's relatives had died of
      fulminant hepatic failure of unknown etiology. The patient improved spontaneously
      but presented reactivation of the disease 3 weeks later and died after splenic
      biopsy.

PMID- 11827657
TI  - [Postraumatic lesion of the carotid artery].
AB  - Postraumatic lesions of the carotid artery are very unusual in the general
      population and are especially rare in children due to the elasticity of their
      vessels. Because clinical expression of these lesions is mild, diagnosis can be
      delayed until the development of neurological signs, which are frequently
      irreversible. Neurological signs can be those of Horner's syndrome, drop attack,
      headache, vertigo, visual disorders, aphasia or transitory ischemic accidents.
      Carotid arterial lesion should be ruled out when the patient shows injuries in
      the soft tissue of the neck, when the neurological examination is incompatible
      with the findings of computed tomography (CT), when late neurological deficits
      develop or when the patient has Horner's syndrome. The patient reported herein
      presented partial motor seizures and hemiplegia 3 days after trauma. The most
      sensitive diagnostic test is angiography. Because this technique is aggressive,
      it is performed when suspicion is based on the results of Doppler sonography, CT
      or angiomagnetic resonance imaging. Treatment must be individualized. Standard
      therapy is anticoagulation but when this is contraindicated or the patient is
      asymptomatic anti-aggregating drugs are used. Thrombolytic treatment is reserved
      for the first few hours after injury. Surgical repair is the treatment of choice
      in patients with pseudoaneurysm. Because inaccessibility is one of the major
      difficulties in this type of surgery, intravascular stents can be a good
      therapeutic alternative in lesions unresponsive to medical treatment.

PMID- 11827658
TI  - [Freeman-Sheldon syndrome: clinical manifestations and anesthetic and surgical
      management].
AB  - We report a new sporadic case of Freeman-Sheldon syndrome. The parents were not
      blood relatives. The boy showed characteristic deformities of distal
      arthrogryposis in the hands and feet, as well as the typical features of
      "whistling face syndrome". In addition, the patient showed other clinical
      manifestations such as a large bilateral inguinal hernia and thoracic cage
      abnormalities. The latter abnormality led to serious episodes of bronchopneumonia
      that delayed the surgical repair of bilateral inguinal hernia. Knowledge of the
      sonographic characteristics of deformities of the extremities is essential to
      reach an early prenatal suspected diagnosis of Sheldon-Freeman syndrome,
      especially in families with a history of the syndrome. We describe the
      preanesthetic management, anesthetic method and surgical technique performed when
      the child was aged 9 months. The delay was due to recurrent episodes of
      bronchopneumonia.

PMID- 11827659
TI  - [Kearns-Sayre syndrome: pediatric neuroradiologic findings in computed tomography
      and magnetic resonance imaging].
AB  - Clinical presentation of mitochondrial disorders is heterogeneous because the
      affected organs are those depending on a high rate of aerobic metabolism. They
      can appear at any age and evolution is progressive. Signs that guide diagnostic
      suspicion, especially in the pediatric age group, are heterogeneous clinical
      presentation and multisystem involvement. Within the spectrum of diseases caused
      by mitochondrial myopathy, there are clearly defined syndromes such as Kearns
      Sayre syndrome. Muscle biopsy shows ragged red fibers and approximately 80 % of
      patients present sporadic deletions in mitochondrial DNA. Imaging studies reveal
      areas of hypointensity in basal ganglia and midbrain that are not visible after
      administration of contrast enhancement in computed tomography, and symmetric T2
      hyperintensity lesions in these areas in magnetic resonance imaging. We present a
      patient with Kearns-Sayre syndrome, in whom radiological alterations were helpful
      in reaching the diagnosis.

PMID- 11827660
TI  - [Pyriform sinus fistulae].
AB  - Pyriform sinus fistulae (PSF) are rare branchial pouch anomalies. In most
      previously described cases the anomaly is located on the left side. PSF should be
      suspected in cervical inflammatory processes (cervical abscesses and types of
      suppurative thyroiditis). We report two cases of acute thyroiditis and deep
      cervical abscesses secondary to PSF, which were diagnosed and treated in our
      hospital in the last 2 years. Both presented inflammatory cervical masses
      associated with painful swallowing, high fever and laboratory findings compatible
      with acute infection. In both cases the diagnosis of PSF was confirmed by barium
      esophagogram. Cervical ultrasonography and computed tomography were also
      performed. The treatment of choice consists of broad-spectrum antibiotic therapy
      during acute exacerbation and subsequent fistulectomy. Definitive surgical
      treatment prevents recurrences.

PMID- 11827661
TI  - [Neonatal sepsis due to anaerobes: Bacteroides capillosus].

PMID- 11827662
TI  - [Moraxella catarrhalis as a cause of osteomyelitis in the infant].

PMID- 11827663
TI  - [Kingella kingae: occult bacteriemia in a child].

PMID- 11827664
TI  - [Reactive arthritis after recent infection with group A beta-hemolytic
      Streptococcus and group B Salmonella].

PMID- 11827665
TI  - [Kikuchi-Fujimoto disease in the inguinal region].

PMID- 11827666
TI  - [The innocence of a smile].

PMID- 11827667
TI  - [11-year-old girl with 12% weight loss in 6 months].

PMID- 11827668
TI  - [Hemophagocytic syndromes: think of them... because they are a reality].

PMID- 11827669
TI  - [Abnormalities in coagulation and fibrinolysis in septic shock with purpura].
AB  - OBJECTIVE: To describe abnormalities in coagulation and fibrinolysis in septic
      shock with purpura and to assess the relationship between plasma plasminogen
      activator inhibitor-1 (PAI-1) concentrations and multiple organ system failure
      (MOSF). METHODS: Observational study in the pediatric intensive care unit of a
      tertiary care hospital. The presence of early MOSF was assessed at admission in
      15 children with septic shock and purpura consecutively admitted to the pediatric
      intensive care unit. Blood samples were taken to determine coagulation and
      fibrinolysis parameters. RESULTS: At admission, MOSF was diagnosed in 7 patients
      (46.7 %), acute respiratory distress syndrome (ARDS) in 6 (40 %), consumption
      coagulopathy in 7 (46.7 %) and acute renal failure in 1 (6.7 %). The overall
      mortality rate was 40 %. Coagulation parameters were generally affected but
      statistically significant differences were found only in concentrations of
      fibrinogen and antithrombin III, which were lower in patients with MOSF than in
      those without organ dysfunction. Fibrinolysis parameters were increased in all
      patients but plasma PAI-1 concentrations were significantly elevated only in
      patients with MOSF and in those with ARDS. CONCLUSION: These data indicate that
      impaired fibrinolysis could play a major role in the development of MOSF in
      children with septic shock and purpura.

PMID- 11827670
TI  - [Acute Gastroenteritis in hospitalized children. 14-Year evolution].
AB  - OBJECTIVES: To analyze the etiology and evolution of patients with acute
      gastroenteritis hospitalized in our pediatric department and to study the
      clinical and laboratory differences between acute viral and bacterial
      gastroenteritis. PATIENTS AND METHODS: We studied the children with a diagnosis
      of acute gastroenteritis, aged between 0 and 14 years, who were consecutively
      admitted between 1987 and 2000. Differences were considered statistically
      significant if p < 0.05. RESULTS: A total of 2,613 patients diagnosed with acute
      gastroenteritis were hospitalized (10.4 % of hospital admissions). The most
      common pathogens isolated were rotaviruses (46.5 %), followed by Salmonella (32.6
      %) and Campylobacter (19.3 %). Hospital admissions due to Salmonella (p <
      0.0001), other bacteria (Escherichia coli and Shigella) (p < 0.002) and
      adenoviruses (p < 0.01) significantly decreased. Rotaviruses were the most
      frequently detected pathogens in winter and in children aged less than 1 year (p
      < 0.0001). The incidence of Salmonella spp was greater in summer and in children
      older than 2 years (p < 0.0001). The incidence of hyperthermia (rectal
      temperature higher than 38.5 degreeC) (p < 0.0001), dehydration (p < 0.0005) and
      fecal blood (p < 0.0001) was higher in bacterial diarrheas. Erythrocyte
      sedimentation rate (p < 0.001) and leukocyte counts were higher in bacterial
      gastroenteritis (p < 0.01). CONCLUSIONS: Rotaviruses were the most frequently
      isolated enteropathogens. The features that best distinguished between bacterial
      and viral diarrhea were hyperthermia and fecal blood. Hospital admissions due to
      Salmonella Shigella E. coli, and adenoviruses significantly decreased.

PMID- 11827671
TI  - [Re-education of the anal sphincter in patients with myelomeningocele].
AB  - OBJECTIVE: The aim of this study was to analyze the usefulness of biofeedback
      techniques based on manometrical procedures in the treatment of defecation
      disorders in patients with myelomeningocele. PATIENTS AND METHODS: We studied 24
      patients with myelomeningocele, aged 13 days to 15 years, who were referred to
      our Instrumental Diagnosis Unit for evaluation of anorectal function, or
      constipation and/or fecal incontinence study. Biofeedback was given to 12
      patients who fulfilled the following criteria: age more than 5 years, existence
      of anorectal sensitivity with a perceptual threshold of less than 60 ml of rectal
      expansion, ability to contract and relax the gluteus muscles and thus be able to
      exercise pressure on the anal margin, and collaboration on the part of child and
      the family. As a complement defecatory maneuvers were performed. RESULTS: Between
      4 and 65 sessions took place (35.14 19.97) after which rectal perceptual volume
      decreased from 24.66 14.13 to 3.33 2.95 ml and pressure on the anal margin
      increased from 45.62 17.82 to 114.37 13.99 mmHg. These differences were
      statistically significant (p < 0.001). Clear clinical improvement was produced in
      10 of 12 patients who achieved good fecal continence with spontaneous
      depositions. Partial improvement was produced in 2 patients. CONCLUSIONS: We
      consider that biofeedback based on manometrical procedures is more useful than
      other conservative therapies in the treatment of defecatory problems in patients
      with myelomeningocele. In most patients this technique produces clinical
      improvement with satisfactory continence and without the drawbacks of other
      procedures.

PMID- 11827672
TI  - [Health and nutritional status of delinquent female adolescents].
AB  - OBJECTIVE: To assess the health and nutritional status of delinquent female
      adolescents on admission to a juvenile correctional facility. METHODS: We
      performed a cross-sectional study over a 6-year period (1995-2000). Health status
      was assessed through medical history and physical examination according to
      standard protocols and individualized complementary laboratory examinations.
      Nutritional status was assessed using the anthropometric method. Height, weight,
      head and upper arm circumferences, body-mass index and nutritional index were
      determined and compared with normal national standards of reference (Z-score).
      Student's single-sample t-test was used to assess statistically significant
      differences. RESULTS: Thirty-five delinquent female adolescents were admitted
      during the study period. Mean age was 15 years (0.72 SDU) (range: 14-17 years).
      The most frequently observed health problems were smoking (n 32), drug/alcohol
      abuse (n 22), high-risk sexual behavior (n 14), psychopathologic disorders (n
      12), odontologic diseases (n 11), infectious diseases associated with intravenous
      drug use and/or high-risk sexual behavior (n 10) [specific vaginitis (n 3),
      bacterial vaginitis (n 2), AIDS (n 2), hepatitis C (n 2), hepatitis B (n 1)] and
      incomplete immunization status (n 6). Less prevalent health problems were iron
      deficiency anemia (n 3), positive pregnancy test (n 2), and dermatological (n 2),
      ophthalmological (n 2) and neurosensorial (n 1) disorders. No respiratory,
      locomotor, otorhinolaryngological, cardiovascular or gastrointestinal disorders
      were observed. Individual and group analysis of established anthropometric
      parameters and indices showed no growth or nutritional disorders. CONCLUSIONS: In
      our environment, delinquent female adolescents arrive at correctional facilities
      with significant physical, psychological and behavioral problems. This population
      is especially in need of psychiatric, dental, gynecologic, infectious, and
      immunization services. The time in custody presents a unique opportunity to
      address the basic health concerns of this high-risk population and to provide
      general health education, including education on substance abuse and sex
      education.

PMID- 11827673
TI  - [New trends in mechanical ventilation].
AB  - Many ventilatory techniques are employed on the Neonatal Intensive Care Unit, but
      there is limited evidence supporting the use, in particular of the more recently
      introduced modes. Randomized trials have demonstrated that high frequency
      positive pressure ventilation reduced airleaks and patient triggered ventilation
      was associated with a shorter duration of ventilation. "Rescue" high frequency
      oscillation was suggested to reduce airleaks and prophylactic high frequency
      oscillation decrease chronic lung disease, but possibly at the expense of
      increased intracerebral pathology. Results from anecdotal series suggest that
      nasal continuous positive airways pressure, volume guarantee and pressure support
      ventilation have advantages, but the techniques have not been subjected to
      rigorous testing in large randomized trials. Neonatologists must not be seduced
      by promising preliminary results. Ventilatory strategies should only be
      introduced into routine clinical practice if proven efficacious and without long
      term adverse effects in appropriately sized studies.

PMID- 11827674
TI  - [Not all vascular birthmarks are angiomas].
AB  - Vascular anomalies are extremely common but for many years have been poorly
      understood, partly due to the complex and colorful terminology used, which is
      full of descriptive terms tinged with folklore. While many lesions look the same,
      they have a very different prognosis and require very different treatment.
      Therefore, it is essential to be precise when using the nomenclature. This
      article reviews the current classification of vascular anomalies and describes
      recent advances in their diagnosis and management. Our aim is to replace the old
      confusing terminology and contribute to the unification of concepts and terms. At
      the same time we stress the importance of interdisciplinary collaboration in
      order to offer patients accessible and integral treatment.

PMID- 11827675
TI  - Language and publication in "Cardiovascular Research" articles.
AB  - BACKGROUND: The acceptance rate of non-mother English tongue authors is generally
      a lot lower than for native English tongue authors. Obviously the scientific
      quality of an article is the principal reason for publication. However, is
      editorial rejection purely on scientific grounds? English mother tongue writers
      publish more than non mother-tongue writers--so are editors discriminating
      linguistically? We therefore decided to survey language errors in manuscripts
      submitted for publication to Cardiovascular Research (CVR). METHOD: We surveyed
      language errors in 120 medical articles which had been submitted for publication
      in 1999 and 2000. The language "error" categories were divided into three
      principal groups: grammatical, structural and lexical which were then further sub
      divided into key areas. The articles were corrected without any knowledge of the
      author's nationality or the corrections made by other language researchers. After
      an initial correction, a sample of the papers were cross-checked to verify
      reliability. RESULTS: The control groups of US and UK authors had an almost
      identical acceptance rate and overall "error" rate indicating that the language
      categories were objective categories also for the other nationalities. Although
      there was not a direct relationship between the acceptance rate and the amount of
      language errors, there was a clear indication that badly written articles
      correlated with a high rejection rate. The US/UK acceptance rate of 30.4% was
      higher than for all the other countries. The lowest acceptance rate of 9%
      (Italian) also had the highest error rate. DISCUSSION: Many factors could
      influence the rejection of an article. However, we found clear indications that
      carelessly written articles could often have either a direct or subliminal
      influence on whether a paper was accepted or rejected. On equal scientific merit,
      a badly written article will have less chance of being accepted. This is even if
      the editor involved in rejecting a paper does not necessarily identify language
      problems as a motive for rejection. A more detailed look at the types and
      categories of language errors is needed. Furthermore we suggest the introduction
      of standardised guidelines in scientific writing.

PMID- 11827676
TI  - Does adenosine protect the heart by acting on the sarcoplasmic reticulum?

PMID- 11827677
TI  - Removal of intracellular Mg(2+) activates cardiac Na(+)/Ca(2+) exchanger.

PMID- 11827678
TI  - New tools for prevention of restenosis could decrease the "oculo-stento" reflex.

PMID- 11827680
TI  - Is angiotensin II a proliferative factor of cardiac fibroblasts?
AB  - Angiotensin II has been implicated as an important factor in cardiac remodeling,
      particularly in the development of pathological left ventricular hypertrophy. It
      is generally assumed that angiotensin II is able to alter the phenotype of
      cardiac myocytes and fibroblasts, and several experiments have suggested that
      this peptide can particularly affect the proliferation of cardiac fibroblasts.
      However, a review of the published results indicates that there is no evidence
      that angiotensin II can directly trigger mitogenesis through activation of the
      cyclin-dependent pathway. The observed proliferative effect might well be caused
      by stimulation of the synthesis of growth or inflammatory substances like
      platelet-derived growth factor and cytokines, by integrin activation due to
      secreted extracellular matrix proteins, or by a combination of these mechanisms.
      Angiotensin II thus appears to differentiate cardiac fibroblasts into a growth
      substance-secreting phenotype.

PMID- 11827679
TI  - Old and new tools to dissect calcineurin's role in pressure-overload cardiac
      hypertrophy.
AB  - In the last several years, a number of experiments have implicated a pivotal role
      of the calcium/calmodulin-calcineurin dependent pathway as a final common
      signaling mechanism by which diverse hypertrophic stimuli converge to mediate
      hypertrophic responses in cardiomyocytes. Calcineurin inhibitors, i.e.
      cyclosporine A (CsA) and FK506, can interrupt the pathway, thereby preventing
      cardiac hypertrophy. The data that convincingly support this novel hypothesis
      were derived either from in vitro studies in cultured cardiomyocytes or from in
      vivo studies in transgenic mice. However, when the hypothesis was tested in
      clinically relevant animal models of cardiac hypertrophy, controversial results
      and conclusions emerged. In conventional models of cardiac hypertrophy, two
      questions remain to be answered: (1) whether calcineurin is activated in
      hypertrophied cardiac muscle, and (2) whether calcineurin inhibitors prevent
      cardiac hypertrophy. In addition, clinical observations have revealed that
      calcineurin inhibitors appear to exert pro-hypertrophic effects in organ
      transplant recipients. The controversies suggest that current calcineurin
      inhibitors are blunt tools for testing the hypothesis in pressure-overload
      hypertrophy in vivo, because there are so many confounding effects that are
      associated with systemic administration of the drugs. As such, new genetic
      approaches may overcome some of the problems associated with pharmacological
      inhibitors. This invited review will focus on the controversies surrounding the
      ability of calcineurin inhibition to prevent conventional (pressure-overload)
      cardiac hypertrophy and the new genetic approaches to address the question.

PMID- 11827682
TI  - Effect of cardiac A(1) adenosine receptor overexpression on sarcoplasmic
      reticulum function.
AB  - OBJECTIVE: We investigated the effect of A(1) adenosine receptor overexpression,
      which has been reported to increase myocardial tolerance to ischemia-reperfusion
      injury, on sarcoplasmic reticulum (SR) Ca(2+) handling. METHODS: Transgenic mouse
      hearts (approximately 300-fold A(1) adenosine receptor overexpression) and wild
      type mouse hearts were perfused in the Langendorff mode and subjected either to
      80 min of aerobic perfusion or to 30 min of aerobic perfusion, 20 min of global
      ischemia and 30 min of reperfusion. The hearts were then homogenized and used to
      assay SR oxalate-supported 45Ca(2+) uptake and [3H]-ryanodine binding. RESULTS:
      Transgenic hearts showed increased resistance to ischemia-reperfusion, as shown
      by lower diastolic tension (1.5 +/- 0.2 vs. 2.6 +/- 0.1 g, P<0.05) and higher
      recovery of developed tension (45 +/- 3 vs. 30 +/- 4% of the baseline, P<0.05)
      following ischemia-reperfusion. Under baseline conditions, oxalate-supported
      45Ca(2+) uptake was lower in transgenic hearts, owing to reduced V(max) (10.6 +/-
      2.0 vs. 17.8 +/- 2.7 nmol/min per mg of protein, P<0.05), and the difference was
      preserved after ischemia-reperfusion (10.0 +/- 1.0 vs. 15.7 +/- 2.5 nmol/min per
      mg of protein, P<0.05). No significant difference in [3H]-ryanodine binding was
      observed. CONCLUSIONS: A(1) adenosine receptor overexpression is associated with
      a decreased rate of active Ca(2+) transport into the SR. We hypothesize that
      changes in SR function may cause a depletion of the SR Ca(2+) pool, which might
      protect from ischemic injury by delaying the development of cytosolic Ca(2+)
      overload during ischemia.

PMID- 11827683
TI  - Cytosolic free magnesium modulates Na/Ca exchange currents in pig myocytes.
AB  - OBJECTIVE: Cardiac Na/Ca exchanger (NCX) protein is up-regulated and
      intracellular free magnesium ([Mg(2+)](i)) is significantly reduced in
      experimental heart failure. We asked whether changes in [Mg(2+)](i) in a
      physiologically relevant range could alter the I(NCX). METHODS: The nickel
      sensitive current was measured in voltage-clamped myocytes (Yorkshire pig; left
      ventricular) exposed to ramp pulses at 37 degrees C in Tyrode's solution
      containing ouabain, nifedipine and +/- Ni(2+) (5 mmol/l). The intracellular free
      [Ca(2+)] and [Mg(2+)] concentrations were set at 50 nmol/l and 1.25 mmol/l (HiMg)
      or 0.13 mmol/l (LoMg), respectively, through pipette dialysis. RESULTS: Reducing
      [Mg(2+)](i) resulted in a significant increase in both outward and inward Ni
      sensitive current without a shift in the reversal potential. This effect was not
      due to the inadvertent reduction of intracellular free [ATP] secondary to binding
      of ATP to Mg(2+); reducing intracellular [ATP] in LoMg cells from 1.35 mmol/l to
      0.18 mmol/l did not affect I(NCX). The intracellular free [Ca(2+)] was raised
      from 50 to 200 nmol/l, resulting in augmented inward and outward current due to
      calcium activation. HiMg attenuated both inward and outward currents
      significantly compared to LoMg, suggesting that [Mg(2+)](i) competes with
      [Ca(2+)](i) at the allosteric regulatory site. CONCLUSION: Cytosolic free
      magnesium modulates the I(NCX) over a physiologic range independent of [ATP](i).
      Reduced [Mg(2+)](i) in heart failure could contribute to altered calcium
      regulation of the NCX, contributing to the altered heart failure phenotype
      through enhanced NCX activity.

PMID- 11827681
TI  - Tissue factor and coronary artery disease.
AB  - Plaque disruption with superimposed thrombosis is the main cause of acute
      coronary events such as acute myocardial infarction and unstable angina. Among
      other factors, tissue factor seems to play an important role determining plaque
      thrombogenicity. Tissue factor is a potent initiator of the coagulation cascade
      situated within the vessel wall and is highly exposed to the blood after plaque
      rupture. Several mediators involved in the process of atherosclerotic plaque
      formation are capable of inducing tissue factor expression in cells such as
      monocytes, macrophages and endothelial cells, which under normal conditions do
      not express tissue factor or to a limited extent only. The increased expression
      of tissue factor is not limited to the plaque but is also found in circulating
      monocytes in patients with acute coronary syndromes. In addition, studies have
      shown an important contribution of tissue factor in the pathogenesis of
      thrombosis and restenosis after balloon angioplasty. Recent basic studies focus
      on the therapeutic inhibition of tissue factor. Specific and non-specific
      inhibitors of tissue factor or the tissue factor/factor VIIa complex have been
      developed or identified, and have been tested in experimental studies. Clinical
      studies are currently being initiated. In this review, we present the current
      knowledge on the role of tissue factor in atherosclerosis, arterial intervention
      and potential pharmacological approaches, with focus on acute coronary syndromes.

PMID- 11827685
TI  - A mutant cardiac sodium channel with multiple biophysical defects associated with
      overlapping clinical features of Brugada syndrome and cardiac conduction disease.
AB  - OBJECTIVE: Loss of Na(+) channel function has been implicated in idiopathic
      ventricular fibrillation (IVF) and Brugada syndrome. We have studied the
      biophysical properties of an IVF mutation (S1710L) that exhibited an unusual
      clinical phenotype: rate-dependent bundle branch block without manifestation of
      Brugada-type ECG pattern. METHODS: The mutant S1710L channels were expressed in
      mammalian cells and their gating properties, studied using whole-cell patch clamp
      techniques, were compared with wild-type (WT) and a Brugada syndrome mutant
      channel T1620M. RESULTS: The S1710L channel exhibited significantly faster
      macroscopic current decay than WT or T1620M. In addition, S1710L showed a
      negative shift in the voltage-dependence of fast inactivation and slower recovery
      from fast inactivation than in WT or T1620M. In addition to the alterations in
      fast inactivation most commonly observed in Brugada syndrome mutations, S1710L
      exhibited marked enhancement in slow inactivation and a large positive shift of
      activation that potentially decreases conduction velocity. CONCLUSIONS: These
      functional abnormalities may be responsible for the overlapping clinical
      phenotypes associated with Brugada syndrome and the cardiac conduction defect, a
      novel cardiac Na(+) channelopathy.

PMID- 11827684
TI  - High plasma concentrations of human urotensin II do not alter local or systemic
      hemodynamics in man.
AB  - OBJECTIVE: Human urotensin II (hUII) is an endocrine hormone that acts as a
      potent arterial vasoconstrictor in both in vitro and in vivo studies in animals.
      We examined, for the first time, the local and systemic hemodynamic response to
      hUII in man in vivo. METHODS: Four healthy male volunteers took part in pilot
      studies and 11 in definitive studies. Forearm blood flow (FBF) was measured in
      response to intra-arterial infusion of authentic, biologically active hUII
      (incremental rates of 0.001-300 pmol min(-1)) and saline placebo using venous
      occlusion plethysmography. Blood pressure, heart rate, cardiac output and hUII
      plasma concentrations were also measured. Forearm studies were repeated in five
      subjects with inhibition of endothelial mediators using aspirin and a "nitric
      oxide clamp". Dorsal hand vein diameter was determined by a standard displacement
      technique in response to local administration of hUII (3-300 pmol min(-1)) with
      and without nitric oxide synthase inhibition. RESULTS: There was no significant
      change in FBF during brachial infusion of saline or hUII (dose range, 0.001 to
      300 pmol min(-1)). A nitric oxide clamp did not unmask vasoactive effects of
      hUII. Human UII infusions (100 and 300 pmol min(-1)) significantly increased
      plasma hUII concentrations from baseline (12 +/- 3 pmol l(-1)) to 106 +/- 15 and
      307 +/- 98 pmol l(-1), respectively. Despite high circulating hUII
      concentrations, no change was seen in systemic hemodynamics and ECGs were
      unchanged. Human UII had no effect on hand vein diameter (n=6). CONCLUSIONS: In
      contrast to our hypothesised role of hUII, we found no vasoactive responses to
      hUII in vivo, consistent with recent in vitro studies in human blood vessels, but
      in contrast to non-human primate studies in vivo. Our data do not support a key
      role for hUII in the regulation of vascular tone and resting blood pressure in
      man. However, studies with hUII receptor antagonists are also needed before firm
      conclusions can be drawn.

PMID- 11827686
TI  - Rapid component I(Kr) of the guinea-pig cardiac delayed rectifier K(+) current is
      inhibited by beta(1)-adrenoreceptor activation, via cAMP/protein kinase A
      dependent pathways.
AB  - OBJECTIVE: The antiarrhythmic potential of betablockers contributes to their
      beneficial effects in the treatment of cardiac diseases, although the molecular
      basis of their class II antiarrhythmic action has not been clarified yet.
      METHODS: To investigate a putative functional link between beta-adrenoreceptors
      and the fast component of cardiac delayed rectifier K(+) channels (I(Kr)), whole
      cell patch-clamp experiments were performed with isolated guinea-pig ventricular
      myocytes. Tail currents of I(Kr) were measured at -40 mV after short (200 ms)
      test pulses to +40 mV. RESULTS: After application of the unspecific beta-receptor
      agonist isoproterenol (10 microM) for 12 min, the I(Kr) tail current was
      decreased by 72%, with an IC(50) of 1.4 microM. The specific beta(1)-blocker
      CGP207120A (10 microM) significantly attenuated the isoproterenol effect (net 24%
      decrease). The specific beta(1)-agonist xamoterol (10 microM), could mimic the
      isoproterenol effect (58% decrease). Modulators of beta(2)- or beta(3)
      adrenoreceptors were far less effective. When isoproterenol or xamoterol were
      combined with KT5720 (2.5 microM), a specific inhibitor of protein kinase A
      (PKA), their effects were drastically reduced, indicating that PKA presumably
      mediates the beta(1)-adrenergic inhibition of I(Kr). Tail current reductions by
      cAMP, forskolin, PKA catalytic subunit and a combination of PKA holoenzyme and
      cAMP support an involvement of PKA in the regulation of I(Kr). CONCLUSIONS: The
      functional link between I(Kr) and the beta(1)-adrenergic receptor involving PKA
      may play an important role in arrhythmogenesis and contribute to the
      antiarrhythmic action of clinically used beta(1)-blockers.

PMID- 11827687
TI  - Activation of the cardiac endothelin system in left ventricular hypertrophy
      before onset of heart failure in TG(mREN2)27 rats.
AB  - OBJECTIVE: To characterize the cardiac angiotensin and endothelin (ET) system in
      compensated left ventricular hypertrophy due to long standing arterial
      hypertension and to assess the role of angiotensin and ET converting enzymes in
      mediating the observed changes of angiotensin and ET levels, respectively.
      METHODS: We studied the left ventricular renin-angiotensin system (RAS) and ET
      system in 20-week-old male transgenic hypertensive TG(mREN2)27 rats, a model of
      the monogenic renin-dependent form of severe hypertension. Age-matched Sprague
      Dawley rats served as controls. RESULTS: TG(mREN2)27 rats exhibited left
      ventricular hypertrophy without signs of congestion. Transgene overexpression led
      to an activation of the tissue RAS with increased angiotensin II levels in spite
      of unchanged angiotensin converting enzyme (ACE) activity and ACE mRNA levels. ET
      1 production was markedly increased in TG(mREN2)27 rats indicating that the ET
      system was activated. Cardiac ET-1 in TG(mREN2)27 originated most likely from
      increased preproET-1 production because preproET-1 mRNA levels were increased but
      ET converting enzyme gene expression and activity were unchanged. Furthermore, ET
      1 binding sites were significantly increased in TG(mREN2)27 rats without changes
      in K(D) values and ET(A)/ET(B) receptor ratios. ET(A) receptor gene expression
      was not altered whereas ET(B) receptor mRNA levels were up-regulated twofold in
      TG(mREN2)27 rats suggesting that ET(A) and ET(B) receptor expression may be
      regulated differentially. CONCLUSIONS: Cardiac ET and angiotensin systems are co
      activated in compensated cardiac hypertrophy before onset of heart failure, and
      thus may be involved in the mechanism by which cardiac remodelling and
      progression of left ventricular dysfunction occur in TG(mREN2)27 rats.

PMID- 11827688
TI  - Hypertrophy and functional alterations in hyperdynamic phospholamban-knockout
      mouse hearts under chronic aortic stenosis.
AB  - OBJECTIVE: To determine whether the hyperdynamic phospholamban-knockout hearts
      are capable of withstanding a chronic aortic stenosis. METHODS: The transverse
      section of the aorta was banded in phospholamban-knockout and their isogenic wild
      type mice, which were followed with echocardiography in parallel, along with sham
      operated mice, before and at 2.5, 5 and 10 weeks after surgery. RESULTS: Cardiac
      decompensation was evidenced by the presence of lung congestion in some banded
      knockouts and wild-types, giving rise to a subset of non-failing and failing
      hearts within each group. The incidence of heart failure was not genotype
      dependent but rather associated with higher heart rates before surgery. The
      development of left ventricular hypertrophy was similar between knockouts and
      wild-types and longitudinal assessment of end-diastolic dimension indicated
      progressive increases after banding, with a greater dilation in failing mice.
      Fractional shortening was reduced in failing knockouts and wild-types to a
      similar degree, with an earlier onset in the knockouts. In addition, fractional
      shortening was decreased in non-failing knockouts but not wild-types. Ejection
      times shortened after aortic banding particularly for failing hearts. Assessment
      of the SR Ca(2+)-ATPase protein levels indicated similar downregulation for
      failing knockouts and wild-types, while the phospholamban levels were not
      significantly altered in wild-types. CONCLUSION: The hyperdynamic phospholamban
      knockout hearts are able to compensate against a sustained aortic stenosis
      similar to wild-types.

PMID- 11827689
TI  - Reduced level of serine(16) phosphorylated phospholamban in the failing rat
      myocardium: a major contributor to reduced SERCA2 activity.
AB  - OBJECTIVE: Heart failure is associated with alterations in contractile parameters
      and accompanied by abnormalities in intracellular calcium homeostasis.
      Sarcoplasmic reticulum Ca(2+) ATPase (SERCA2) and phospholamban (PLB) are
      important in intracellular calcium cycling. The aim of the present study was to
      examine mechanisms causing reductions in SERCA2 activity in the failing heart.
      METHODS: Myocardial infarction (MI) was induced in male Wistar rats, and animals
      with congestive heart failure were examined 6 weeks after the primary operation.
      RESULTS: Serine(16) monomeric and pentameric phosphorylated PLB were
      significantly downregulated (50 and 55%, respectively), whereas threonine(17)
      phosphorylated PLB was unchanged in failing compared to sham hearts. Protein
      phosphatases 1 and 2A were significantly upregulated (26 and 42%, respectively)
      and phosphatase 2C significantly downregulated (29%), whereas the level of
      protein kinase A regulatory subunit II remained unchanged during heart failure.
      Increasing PLB phosphorylation by forskolin in isolated cardiomyocytes after
      inhibition of the Na(+)-Ca(2+) exchanger activity had significantly greater
      effect on SERCA2 activity in failing than in sham cells (49 and 20% faster
      transient decline, respectively). Decreasing PLB phosphorylation by the protein
      kinase A inhibitor H89 had significantly less effect on SERCA2 activity in
      failing compared to sham cardiomyocytes (20 and 75% slower transient decline,
      respectively). CONCLUSION: The observed changes in SERCA2 activity after
      increasing and decreasing serine(16) PLB phosphorylation in cardiomyocytes from
      sham and failing hearts, suggest that the observed reduction in serine(16) PLB
      phosphorylation is one major factor determining the reduced SERCA2 activity in
      heart failure after MI.

PMID- 11827690
TI  - Catecholamine stimulation is associated with impaired myocardial O(2) utilization
      in heart failure.
AB  - OBJECTIVES: To investigate the effect of alpha,beta(1) and beta(2) adrenergic
      receptor (AR) stimulation on coronary hemodynamics, myocardial oxygen consumption
      (M(v)O(2)) and metabolic substrate preference in advanced dilated cardiomyopathy
      (DCM). METHODS: We studied 19 conscious, instrumented dogs with pacing-induced
      DCM. We evaluated systemic, coronary hemodynamics and M(v)O(2) in response to
      norepinephrine (NOR, 0.05-0.4 microg/kg per min), dobutamine (DOB, 1-10 microg/kg
      per min), phenylephrine (PHE, 1-5 microg/kg per min) and isoproterenol (ISO, 0.05
      0.4 microg/kg per min) alone or in the presence of metoprolol (ISO+MET).
      Experiments were conducted in control state and in advanced DCM, 4-5 weeks after
      the initiation of pacing. RESULTS: Contractile responses (LV dP/dt) to
      catecholamines were desensitized and accompanied by a parallel decrease in heart
      rate-adjusted myocardial O(2) consumption (M(v)O(2/beat)), when alpha(PHE) or
      beta(1) (DOB) or both alpha/beta(1) (NOR) AR were stimulated in DCM. This was due
      to impaired transmyocardial (Ao-Cs) O(2) extraction rather than limitations in
      CBF responses. There was an associated shift in myocardial metabolism, evidenced
      by an increased preference for glycolytic substrates (Respiratory Quotient)
      following administration of any of these three adrenergic agonists in DCM.
      Combined beta(1)/beta(2) stimulation with ISO or beta(2)-AR stimulation (ISO+MET)
      in DCM resulted in greater M(v)O(2/beat), [(Ao-Cs) O(2)] extraction, and
      decreases in myocardial RQ consistent with a shift toward oxidation of FFA.
      CONCLUSIONS: The impairment in contractile responses to dobutamine and
      norepinephrine in DCM is associated with impaired myocardial O(2) extraction, and
      a shift toward a preference for glycolysis. A different myocardial metabolic
      pattern suggestive of increased oxidation of FFA with increased myocardial O(2)
      extraction was observed in the presence of combined beta(1)/beta(2) stimulation
      with isoproterenol or beta(2) stimulation (ISO+MET). These data suggest that
      beta(2)-AR stimulation in DCM shifts substrate preference toward FFA oxidation
      associated with greater M(v)O(2) requirements. These findings identify a putative
      metabolic effect of beta(2) -AR in DCM that may be deleterious.

PMID- 11827691
TI  - Nitric oxide as a mediator of delayed pharmacological (A(1) receptor triggered)
      preconditioning; is eNOS masquerading as iNOS?
AB  - BACKGROUND: Nitric oxide (NO), synthesised from the inducible isoform of nitric
      oxide synthase (iNOS), is implicated in mediating second window of protection
      (SWOP)/delayed ischemic preconditioning. However the role of NO and iNOS in
      delayed pharmacological protection remains unclear and is the subject of this
      investigation. METHODS: To test the hypothesis that iNOS is necessary for delayed
      pharmacological preconditioning, the adenosine A(1) receptor agonist, 2-chloro
      N(6) cyclopentyl adenosine (CCPA) (25 microg/kg i.v.) or saline was administered
      to wild type (WT) or iNOS gene knockout mice (KO). Twenty-four hours later, the
      hearts were isolated, Langendorff perfused and subjected to 35 min ischemia/30
      min reperfusion prior to infarct size determination. RESULTS: WT and KO control
      hearts had identical infarct sizes of 37 +/- 3% and 37 +/- 2%, respectively. CCPA
      significantly reduced infarct size in WT hearts to 22 +/- 2% and also,
      unexpectedly, in KO hearts (27 +/- 2%). This protection was abrogated with the
      non-specific NOS inhibitor, N(omega) nitro L-arginine methyl ester (L-NAME, 100
      microM), and could be mimicked in naive hearts with the NO donor, donor S-nitroso
      N-acetyl DL penicillamine (SNAP, 1 microM). Delayed protection appeared to be
      mediated by NO synthesis in both WT and KO hearts. Additional studies using
      Western blot analysis demonstrated endothelial NOS (eNOS) upregulation and
      increased NO(x) release in both WT and KO hearts. CONCLUSIONS: This is the first
      study to demonstrate a role for eNOS in delayed A(1) receptor triggered
      (pharmacological) preconditioning, potentially representing a new pharmacological
      target for protecting the ischemic heart.

PMID- 11827692
TI  - p38 MAPK inhibition reduces myocardial reperfusion injury via inhibition of
      endothelial adhesion molecule expression and blockade of PMN accumulation.
AB  - BACKGROUND: In vitro evidence suggests that the p38 mitogen-activated protein
      kinase (p38 MAPK) plays a crucial role in PMN activation and inflammatory
      cytokine production. However, the effect of p38 MAPK on myocardial reperfusion
      injury, a pathologic condition involving a typical inflammatory response, has not
      been fully examined. In the present study, we investigated the effect of SB
      239063, a specific p38 MAPK inhibitor, on myocardial injury in a murine
      ischemia/reperfusion (I/R) model and elucidated the mechanism by which p38 MAPK
      inhibitor may exert its protective effect against I/R injury. METHODS AND
      RESULTS: I/R resulted in a significant myocardial injury (myocardial infarct 45
      +/- 2.9%) and marked PMN accumulation (myeloperoxidase activity 1.03 +/- 0.16
      U/100 g tissue). Administration of SB 239063 significantly inhibited the
      myocardial inflammatory response as evidenced by reduced PMN accumulation in I/R
      myocardial tissue (0.62 +/- 0.008 U/100 g tissue, P<0.01 vs. vehicle), and
      markedly attenuated myocardial reperfusion injury (myocardial infarct size: 28 +/
      2.4%, P<0.01 vs. vehicle). Moreover, treatment with SB 239063 significantly
      attenuated I/R-induced P-selectin and ICAM-1 upregulation (13.8 +/- 2.7 vs. 23.9
      +/- 3.1%, and 29.4 +/- 1.6 vs. 56.3 +/- 4.8%, respectively P<0.01). In addition,
      pre-treatment with R15.7, a monoclonal antibody against CD 18 adhesion molecule
      on PMN surface that virtually abolished PMN accumulation in ischemic-reperfused
      myocardial tissue, significantly, but not completely, blocked the
      cardioprotection exerted by SB 239063. CONCLUSION: These results demonstrated for
      the first time that p38 MAPK activation plays a significant role in adhesion
      molecule upregulation on ischemia-reperfused endothelial cells and is an
      important signaling step in the pathogenesis of PMN-mediated tissue injury.

PMID- 11827693
TI  - Elevated hexokinase increases cardiac glycolysis in transgenic mice.
AB  - OBJECTIVE: Cardiac glucose metabolism is critical to normal and pathological
      function. The significance of the first committed metabolic step, glucose
      phosphorylation, has not been established. In this study a new transgenic model
      was developed in order to investigate the importance of this enzymatic step in
      cardiac glycolysis. METHODS: Transgenic mice were produced that overexpress yeast
      hexokinase B under the control of a cardiac specific promoter. Yeast hexokinase B
      is a high affinity enzyme that is not inhibited by glucose-6-phosphate.
      Hexokinase enzyme activity was measured by a modified radiometric procedure.
      Cardiac glucose metabolism and contractility were measured in the Langendorff
      mode. Cardiac glycogen content and glucose-6-phosphate independent glycogen
      synthase activity were also determined. RESULTS: In transgenic hearts hexokinase
      activity was significantly elevated and increased glucose metabolism,
      particularly in the presence of insulin and during cardiac reperfusion. However
      during ischemic perfusion the effect of the transgene on glycolysis was minimal.
      Under all conditions tested there was no effect of hexokinase on contractility.
      Glycogen content of transgenic hearts was elevated 2-fold and glucose-6-phosphate
      independent glycogen synthase was also increased. CONCLUSION: These results
      demonstrate that glucose phosphorylation is a key step in determining cardiac
      glucose metabolism under oxidative conditions.

PMID- 11827694
TI  - Role of protein kinase C- or RhoA-induced Ca(2+) sensitization in stretch-induced
      myogenic tone.
AB  - OBJECTIVE: It has been suggested that Ca(2+) sensitization mechanisms might
      contribute to myogenic tone. However, specific mechanisms have yet to be fully
      identified. Therefore, we investigated the role of protein kinase C (PKC)- or
      RhoA-induced Ca(2+) sensitization in myogenic tone of the rabbit basilar vessel.
      METHODS: Myogenic tone was developed by stretch of rabbit basilar artery. Fura-2
      Ca(2+) signals, contractile responses, PKC immunoblots, translocation of PKC and
      RhoA, and phosphorylation of myosin light chains were measured. RESULTS: Stretch
      of the resting vessel evoked a myogenic contraction and an increase in the
      intracellular Ca(2+) concentration ([Ca(2+)](i)) only in the presence of
      extracellular Ca(2+). Stretch evoked greater contraction than high K(+) at a
      given [Ca(2+)](i). The stretch-induced increase in [Ca(2+)](i) and contractile
      force were inhibited by treatment of the tissue with nifedipine, a blocker of
      voltage-dependent Ca(2+) channel, but not with gadolinium, a blocker of stretch
      activated cation channels. The PKC inhibitors, H-7 and calphostin C, and a RhoA
      activated protein kinase (ROK) inhibitor, Y-27632, inhibited the stretch-induced
      myogenic tone without changing [Ca(2+)](i). Immunoblotting using isoform-specific
      antibodies showed the presence of PKCalpha and PKCepsilon in the rabbit basilar
      artery. PKCalpha, but not PKCepsilon, and RhoA were translocated from the cytosol
      to the cell membrane by stretch. Phosphorylation of the myosin light chains was
      increased by stretch and the increased phosphorylation was blocked by treatment
      of the tissue with H-7 and Y-27632, respectively. CONCLUSIONS: Our results are
      consistent with important roles for PKC and RhoA in the generation of myogenic
      tone. Furthermore, enhanced phosphorylation of the myosin light chains by
      activation of PKCalpha and/or RhoA may be key mechanisms for the Ca(2+)
      sensitization associated myogenic tone in basilar vessels.

PMID- 11827695
TI  - Hearts from mice lacking desmin have a myopathy with impaired active force
      generation and unaltered wall compliance.
AB  - OBJECTIVE: Desmin intermediate filaments are key structures in the cytoskeleton
      of cardiac muscle. Since they are associated with Z-discs and intercalated discs,
      they may have a role in sarcomere alignment or force transmission. We have
      explored the mechanical function of the desmin filaments in the cardiac wall by
      comparing desmin-deficient (Des-/-) and wild-type (Des+/+) mice. METHODS: The
      Langendorff technique was used to examine the contractility of the whole heart.
      Rate of force generation, Ca(2+)-sensitivity and force per cross-sectional area
      were measured in skinned ventricle muscle preparations. RESULTS: Des-/- mice have
      a cardiomyopathy with increased heart weight. Diastolic pressure was increased at
      all filling volumes in the Des-/- group. Since passive wall stress (i.e. force
      per area) was unchanged, the alteration in diastolic pressure is a consequence of
      the thicker ventricle wall. Developed pressure, rate of pressure increase and
      developed wall stress were significantly reduced, suggesting that active force
      generation of the contractile apparatus is reduced in Des-/-. Concentrations of
      actin and myosin in the ventricle were unaltered. Measurements in skinned muscle
      preparations showed a lower active force development with unaltered Ca(2+)
      sensitivity and rate of tension development. CONCLUSION: It is suggested that the
      intermediate filaments have a role in active force generation of cardiac muscle,
      possibly by supporting sarcomere alignment or force transmission. The desmin
      filaments do not contribute the passive elasticity of the ventricle wall. Des-/-
      mice provide a model for genetic cardiomyopathy where the main factor
      contributing to altered cardiac performance is a decrease in active force
      generation, possibly in combination with a loss of functional contractile units.

PMID- 11827696
TI  - Fibronectin signaling stimulates BNP gene transcription by inhibiting neuron
      restrictive silencer element-dependent repression.
AB  - OBJECTIVE: Brain natriuretic peptide (BNP) is a cardiac hormone mainly
      synthesized in ventricles and its expression is markedly increased in ventricular
      hypertrophy that involves the accumulation of extracellular matrix proteins, such
      as fibronectin (Fn). We recently reported that Fn signaling stimulated BNP
      secretion accompanied by hypertrophic responses in vitro. METHODS: To elucidate
      the regulatory mechanism for BNP gene transcription, we examined cis-acting
      elements downstream of Fn signaling in rat ventricular myocytes transfected with
      either the -1812 human BNP-luciferase reporter gene (-1812hBNP/Luc) or one of
      several truncated forms. RESULTS: A strong cis-repressor element was identified
      between -552 and -522 in myocytes plated on uncoated dishes. This region contains
      a neuron-restrictive silencer element (NRSE)-like element (NRSE(BNP)) that is 90%
      homologous with the NRSE consensus sequence. Neuron-restrictive silencer factor
      (NRSF) is known to bind to NRSE and to silence transcription of genes containing
      NRSE. Deletion of NRSE(BNP) and dominant negative NRSF markedly increased the
      reporter activity in transfected cells, suggesting that the NRSE/NRSF system
      silences basal BNP gene transcription. When myocytes were cultured on Fn-coated
      dishes, the reporter activity of -1812hBNP/Luc was increased by approximately
      600% compared with that on uncoated dishes. Interestingly, truncation from -552
      to -522 reduced the Fn-inducible reporter activity. Moreover, deletion of
      NRSE(BNP) and dominant negative NRSF also inhibited the Fn-inducible reporter
      activity. Electrophoretic mobility shift assays showed that Fn signaling
      inhibited the binding activity of NRSF to NRSE(BNP). CONCLUSION: These results
      suggest that Fn-induced BNP up-regulation in rat ventricular myocytes is due to
      inhibition of NRSE(BNP)-dependent repression of BNP gene transcription.

PMID- 11827697
TI  - TNFalpha decreases alphaMHC expression by a NO mediated pathway: role of E-box
      transcription factors for cardiomyocyte specific gene regulation.
AB  - OBJECTIVE: Tumor necrosis factor alpha(TNFalpha) is thought to play a key role in
      the pathogenesis of cardiac failure. In the myocardium, TNFalpha enhances the
      expression of inducible nitric oxide synthase (iNOS). Nitric oxide (NO) has been
      shown to affect beta-agonist-dependent cardiac contractility and relaxation. It
      is not clear, however, whether TNFalpha mediated NO release has sustained cardiac
      effects, by altering expression of cardiomyocyte specific genes such as alpha
      myosin heavy chain (alphaMHC). METHODS: Neonatal rat ventricular cardiomyocytes
      (CM) were stimulated with TNFalpha and/or the NOS inhibitor nitro-L-arginine (L
      NNA). Protein binding to the E-box enhancer element in the alphaMHC promoter was
      evaluated by electrophoretic mobility shift assay (EMSA) and transcriptional
      activity of the E-box consensus motif was determined by luciferase assay. mRNA
      levels of the endogenous alphaMHC gene were assessed by RT-PCR. In vivo studies
      were performed in transgenic mice with cardiac specific over-expression of
      TNFalpha. RESULTS: CM treated with TNFalpha exhibited decreased levels of
      alphaMHC transcripts (69 +/- 8% of control), the effect of TNFalpha was reversed
      by L-NNA (94 +/- 14% of control). As shown by EMSA, TNFalpha reduced protein
      binding to the alphaMHC E-box enhancer motif via NO dependent pathways. Addition
      of the NO-donor sodium nitroprusside (SNP) to CM nuclear extracts dose
      dependently disrupted protein binding to the alphaMHC E-box. Furthermore,
      exposure of CM to TNFalpha or SNP decreased transcription from an E-box
      luciferase-reporter construct (TNFalpha: 74 +/- 12%; SNP 250 microM: 72 +/- 10%;
      SNP 500 microM: 66 +/- 11% of control). In myocardial tissue of TNFalpha
      transgenic mice, increased nitrotyrosine staining, decreased protein binding to
      the alphaMHC E-box motif and reduced expression of alphaMHC (62 +/- 26%) were
      observed. CONCLUSIONS: The present study shows that TNFalpha reduces alphaMHC
      transcript levels in cardiomyocytes. Our data obtained in cultured CM and in
      TNFalpha transgenic mice support the notion that TNFalpha exerts these effects by
      NO and E-box dependent mechanisms in vitro and possibly in vivo.

PMID- 11827698
TI  - Regulation of sarcolemmal Na(+)/H(+) exchange by hydrogen peroxide in adult rat
      ventricular myocytes.
AB  - OBJECTIVE: To characterise the effects of exogenous H(2)O(2) on sarcolemmal
      Na(+)/H(+) exchanger (NHE) activity and determine the roles of extracellular
      signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38 MAPK)
      and protein kinase C (PKC) in observed effects. METHODS: Sarcolemmal H(+) efflux
      rate (J(H)) was determined by microepifluorescence at a pH(i) of 6.70 in adult
      rat ventricular myocytes, after two consecutive acid pulses in HCO(3)(-)-free
      medium; before the second pulse, cells (n=7-10/group) were exposed to H(2)O(2) or
      vehicle and the change in J(H) (DeltaJ(H)) was used to quantify the change in NHE
      activity. ERK and p38 MAPK activities were determined by immunoblotting with
      phosphospecific antibodies. RESULTS: Relative to control, DeltaJ(H) was increased
      by a 10-min exposure to 100, but not 1 or 10 microM H(2)O(2) (1000 microM was not
      tolerated); 3 or 6 min exposure to 100 microM H(2)O(2) was without effect. ERK
      and p38 MAPK activities were both increased by 100 microM H(2)O(2) (peak at 6
      min); the ERK kinase inhibitor PD98059 (10 microM), but not the p38 MAPK
      inhibitor SB203580 (1 microM), inhibited the H(2)O(2)-induced increase in
      DeltaJ(H). H(2)O(2)-induced ERK activation was inhibited not only by PD98059 (10
      microM), but also by the non-selective tyrosine kinase inhibitor genistein (3-100
      microM), the EGF receptor kinase inhibitor AG1478 (3-300 nM) and the Src family
      kinase inhibitor PP2 (0.1-10 microM). The PKC inhibitors GF109203X (0.3-10
      microM) and chelerythrine (1-30 microM) were without effect on ERK activation,
      although the former abolished the H(2)O(2)-induced increase in DeltaJ(H).
      CONCLUSIONS: Our data demonstrate that, in adult rat ventricular myocytes, (i)
      hydrogen peroxide stimulates sarcolemmal NHE activity, (ii) this response
      requires activation of ERK and PKC, but not p38 MAPK, (iii) ERK activation occurs
      through tyrosine kinase-mediated, but PKC-independent, mechanisms

PMID- 11827699
TI  - Local delivery of low-dose docetaxel, a novel microtubule polymerizing agent,
      reduces neointimal hyperplasia in a balloon-injured rabbit iliac artery model.
AB  - OBJECTIVE: Docetaxel (DOC) is a novel microtubule polymerizing agent, with
      superior antiproliferative properties as compared to paclitaxel. DOC is therefore
      a potential therapeutic tool for the prevention of restenosis following
      angioplasty. However, DOC has systemic toxicity such as leukocytopenia, which
      occurs in a dose-dependent manner. To minimize such adverse effects, we carried
      out local delivery of low-dose DOC directly to injured vessel sites. METHODS: The
      rabbit iliac artery was denuded, and then DOC (2 mg) or control vehicle was
      administered locally 20 min, via a local drug delivery catheter. RESULTS: The
      levels of DOC in the plasma were within ng/ml range, eliminating hematopoietic
      side effects. Seven days after the local delivery (DOC: n=4, control: n=4), DOC
      decreased the number of Ki-67-labeled cells in the intima (DOC: 22 +/-10 vs.
      control: 66 +/- 18 cells/mm(2), P<0.01), indicating a decreased proliferative
      activity. At 28 days (DOC: n=8, control: n=8), computer-assisted morphometric
      analysis demonstrated that DOC significantly reduced the intimal area (DOC: 0.15
      +/- 0.13 vs. control: 0.70 +/- 0.13 mm(2), P<0.01). There was also a decrease in
      medial area in the DOC-treated vessels (DOC: 0.62 +/- 0.17 vs. control: 1.13 +/-
      0.38 mm(2), P<0.01). CONCLUSIONS: Local delivery of DOC, even after a single low
      dose administration, effectively inhibits neointimal hyperplasia. Such
      administration is associated with a minimal likelihood of systemic adverse
      effects (leukocytopenia), but potentially induces local toxicity (a decrease in
      medial wall thickness) due to extensive cytotoxic effect.

PMID- 11827700
TI  - Chronic ET(A) receptor blockade prevents endothelial dysfunction of small
      arteries in apolipoprotein E-deficient mice.
AB  - OBJECTIVE: This study investigated whether endothelial dysfunction occurs in
      mesenteric arteries of apoE-deficient mice and determined the role of endothelin
      (ET)-1, which is increased in human atherosclerosis, using an orally active
      endothelin ET(A) receptor antagonist. METHODS: ApoE-deficient and C57BL/6J
      control mice were fed for 30 weeks with normal chow or high-fat Western-type diet
      alone or in combination with darusentan (LU135252; 50 mg/kg/day). Vasomotor
      reactivity of isolated small mesenteric arteries (I.D. 200-250 microm) was
      studied in vitro under perfused and pressurized conditions. RESULTS: In both
      mouse strains, about one fourth of the endothelium-dependent relaxant response to
      acetylcholine was insensitive to inhibition by L-NAME and indomethacin. In
      mesenteric arteries of apoE-deficient mice on Western-type diet, increased intima
      media thickness and levels of endothelin-1 protein were observed. In addition, NO
      mediated endothelium-dependent relaxation to acetylcholine was reduced without
      affecting L-NAME/indomethacin insensitive relaxation and contractions to
      endothelin-1 and serotonin were enhanced. Treatment with darusentan normalized
      vascular structure, NO-mediated relaxation to acetylcholine and contractions to
      endothelin-1 and serotonin without affecting blood pressure or plasma cholesterol
      levels. CONCLUSIONS: Severe hypercholesterolemia in apoE-deficient mice is
      associated with attenuation of NO-mediated relaxation to acetylcholine and
      increased vascular endothelin-1 content. Chronic ET(A) receptor blockade may
      provide a new therapeutic approach to improve NO-mediated endothelium-dependent
      vasomotion in small arteries.

PMID- 11827701
TI  - Insulin resistance but not hypertriglyceridemia per se is associated with
      endothelial dysfunction in chronic hypertriglyceridemia.
AB  - OBJECTIVES: To infer the relative impact of elevated triglyceride levels and
      insulin resistance on endothelial dysfunction in patients with chronic
      hypertriglyceridemia (HTG). METHODS: Endothelial function was studied in 11 HTG
      patients and 16 normolipidemic controls. Cumulative-dose infusions of 5
      hydroxytryptamine (5HT) and sodium nitroprusside were infused locally into the
      brachial artery to study endothelium-dependent and endothelium-independent
      vasodilation, respectively. Data of the HTG patients were dichotomized around the
      median of insulin resistance, calculated as HOMA-index, forming HTG groups with
      mild (HTG-MIR) and severe insulin resistance (HTG-SIR). RESULTS: HTG patients had
      higher triglyceride levels and smaller LDL particle size than controls (both P<
      or =0.001), whereas these parameters did not differ between both HTG groups.
      Insulin resistance was higher in both HTG groups than in controls (11.1 (7.0
      14.5) and 4.9 (4.0-6.7) vs. 2.4 (4.9-5.2), respectively, both P<0.001).
      Similarly, free fatty acid levels, another indicator of insulin resistance, were
      highest in the HTG-SIR group, followed by those in the HTG-MIR and control group
      (0.7 (0.6-0.8), 0.5 (0.4-0.6) and 0.4 (0.3-0.4) mmol/l, respectively, all
      P<0.05). Endothelial-dependent vasodilation was similar in HTG-MIR and controls.
      In contrast, the response to 5HT was attenuated in the HTG-SIR group compared to
      controls (low and high dose by, respectively, -60 and -44%, both P<0.01), and
      tended to be lower than in the HTG-MIR group (-43%, P=0.068 and -41%, P=0.100,
      respectively). Endothelium-independent vasodilation did not differ between the
      three groups. CONCLUSION: These findings indicate that chronic
      hypertriglyceridemia per se is not associated with endothelial dysfunction. In
      contrast, the presence of insulin resistance, characterized by hyperinsulinemia
      and FFA elevation, contributes to the induction of endothelial dysfunction in
      chronic HTG.

PMID- 11827702
TI  - Endothelial cell seeding influences lesion development following arterial injury
      in the cholesterol-fed rabbit.
AB  - OBJECTIVE: A functionally intact endothelial monolayer is thought to be critical
      for the adaptive process of vascular remodeling. This study was undertaken to
      examine the hypothesis that endothelial restoration is a critical determinant of
      remodeling after balloon angioplasty. METHODS: Rabbits (N=12) were fed a
      cholesterol-supplemented diet (0.5%) and were subjected to bilateral balloon
      catheter injury of the iliofemoral arteries. At the time of injury, autologous
      venous endothelial cells (ECs) were implanted on one artery; the contralateral
      vessel served as control. A mean of 42 days after injury, arteriography was
      performed, followed by vessel harvest and histologic analysis. RESULTS: High
      grade (> or =70%) stenoses or occlusion were present in 55% of control and none
      of the EC-seeded arteries. EC-seeding was associated with improved mean (1.0 +/-
      0 vs. 0.7 +/- 0.1, P<0.001) and minimal (0.7 +/- 0.1 vs. 0.4 +/- 0.1, P<0.001)
      luminal diameters by angiography. Seeded arteries demonstrated decreased medial
      area (0.69 +/- 0.04 vs. 1.04 +/- 0.09 mm(2), P<0.001), a more uniform range of
      final lumen area (P<0.0001), and a positive remodeling index. Neointimal area was
      not significantly different. Stenoses were characterized primarily by larger
      neointimal area (2.02 +/- 0.18 vs. 1.38 +/- 0.09 mm(2), stenotic vs. non
      stenotic, P<0.005). Final lumen area was strongly influenced by both neointimal
      growth and vessel remodeling. CONCLUSIONS: These data support the concept that
      endothelial restoration is a critical determinant of the outcome of vessel wall
      repair, particularly in the context of hypercholesterolemia.

PMID- 11827703
TI  - Hypercholesterolemia induces regression in neointimal thickening due to apoptosis
      of vascular smooth muscle cells in the hamster endothelial injury model.
AB  - OBJECTIVE: Hypercholesterolemia is a major risk factor in the development of
      atherosclerosis. Although matrix metalloproteinase may play a key role in plaque
      rupture, apoptosis of vascular smooth muscle cells (VSMCs), which is induced by
      cholesterol and its oxides may also contribute to instability and rupture of
      plaque. Thus, we investigated the roles of hypercholesterolemia in vascular
      remodeling following endothelial injury in the hamster femoral artery. METHODS:
      The endothelium was injured by photochemical reaction between green light and the
      photosensitizer dye, Rose Bengal. Photochemical reaction is routinely used in our
      laboratory to produce endothelial injury without mechanical stretching in
      experimental animals. RESULTS: In normocholesterolemic hamsters (NCH), neointimal
      thickening gradually progressed within a 3-week observation period after
      endothelial injury. In hypercholesterolemic hamsters (HCH), neointimal thickening
      gradually progressed until the second week after endothelial injury. In contrast,
      at the third week neointimal thickening regressed and was thinner than that at
      the second week. There was no significant difference in in vivo proliferation of
      VSMCs detected by in vivo BrdU uptake between HCH and NCH. Apoptotic cells in the
      neointima and the media were observed in HCH from 2 to 4 weeks after endothelial
      injury, but not in NCH. At 2 weeks after endothelial injury, the numbers of TUNEL
      positive VSMCs in HCH were significantly higher than those in NCH (neointima; 1.2
      +/- 0.3 vs. 0.3 +/- 0.1%, P<0.05, media; 2.9 +/- 0.6 vs. 0.6 +/- 0.2%, P<0.01).
      Cholesterol deposit, which is detected by oil red O staining was observed in a
      neointimal or medial area in HCH, but not in NCH. CONCLUSIONS: These findings
      suggest that hypercholesterolemia with endothelial injury may induce VSMC
      apoptosis, followed by the regression of neointimal thickening, further
      hypercholesteremia might play a role in inducing plaque rupture through apoptosis
      of VSMC.

PMID- 11827704
TI  - OxLDL upregulates CXCR2 expression in monocytes via scavenger receptors and
      activation of p38 mitogen-activated protein kinase.
AB  - OBJECTIVE: Chemokine receptor CXCR2 has been implied to play a substantial role
      in pathogenesis of atherosclerosis, but the underlying molecular mechanisms
      remain to be clarified. In the present study, we examined the modulating effect
      of oxLDL on expression of CXCR2 and its functional effect in monocytes. METHODS
      AND RESULTS: OxLDL (20-microg protein/ml), but not LDL (80-microg protein/ml),
      upregulated the surface expression of the CXC chemokine receptor CXCR2 (measured
      by flow cytometry) in both human freshly peripheral blood monocytes and human
      monocytic U937 cells. OxLDL, but not LDL, increased CXCR2 mRNA determined by RT
      PCR in both cells. Treatment of oxLDL (40-microg protein/ml) enhanced chemotaxis
      of U937 cells to IL-8 and their adhesion to an endothelial cell line, ECV304
      (both P<0.05 vs. control). Pretreatment of monocytes with scavenger receptor
      inhibitors, polyinosinic acid (100 microg/ml) and dextran sulfate (50 microg/ml)
      attenuated CXCR2 expression, but pertussis toxin or cholera toxin had no effect.
      OxLDL induced the activation of p38MAPK in monocytes, and this effect of oxLDL
      was blocked by the scanvenger receptor inhibitors. Furthermore, p38 MAPK
      inhibitors SB203580 or SK&F86002 markedly reduced oxLDL-induced CXCR2 expression.
      CONCLUSIONS: This observation demonstrated that oxLDL upregulates CXCR2
      expression in monocytes and promotes the chemotaxis and adhesion of monocytes.
      The effect of oxLDL is mediated through scavenger receptor and p38 MAPK
      activation.

PMID- 11827705
TI  - On key lesions and all that: a tribute to Paul Lohman.
AB  - This paper is a tribute to Paul Lohman at the occasion of his retirement from the
      position of Professor in the Medical Faculty at the Leiden University in The
      Netherlands and as Director of its Department of Radiation Genetics and Chemical
      Mutagenesis. Paul's contributions to the science of genetic toxicology are
      discussed in the context of more recent insights as to how mammalian cells
      process DNA damage, and how this may lead to cancer and, possibly, aging.
      Starting with his work on the characterization of UV-induced DNA repair in
      cultured cells from xeroderma pigmentosum patients and the development of
      methodology for monitoring the removal of UV-induced lesions in human cells, the
      concept of the key lesion is introduced. Among the myriad of DNA lesions that can
      be induced in DNA as a consequence of exposure to a range of natural or synthetic
      mutagens, key lesions are the ones responsible for subsequent adverse effects,
      for example, because they give rise to mutation. The development of methods using
      immunofluorescence microscopy to detect and identify such key lesions and
      quantitate them at the single cell level, is one of the highlights of Paul's
      career. Based on the perceived need to evaluate mutational end points in vivo in
      relation to specific lesions identified by his immunofluorescence methods, Paul
      subsequently made crucial contributions to the development of the first
      transgenic mouse model to measure mutations in chromosomally integrated reporter
      genes. In parallel to his experimental work, Paul greatly contributed to genetic
      toxicology at the theoretical level by his work on the development and evaluation
      of methods for assessment or prediction of risks of exposure to environmental
      mutagens. Finally, Paul has served the discipline of genetic toxicology in a more
      administrative role in various ways, both locally as one of the founders of the
      Medical Genetics Center South-West Netherlands and internationally by playing a
      prominent role in organizations such as ICPEMC. Here, his numerous contributions
      to the journal Mutation Research, both as author on many papers and as Executive
      Managing Editor should not go unmentioned.

PMID- 11827706
TI  - Effects of irradiated medium with or without cells on bystander cell responses.
AB  - Recent studies have indicated that extranuclear or extracellular targets are
      important in mediating the bystander genotoxic effects of alpha-particles. In the
      present study, human-hamster hybrid (A(L)) cells were plated on either one or
      both sides of double-mylar dishes 2-4 days before irradiation, depending on the
      density requirement of experiments. One side (with or without cells) was
      irradiated with alpha-particles (from 0.1 to 100 Gy) using the track segment mode
      of a 4 MeV Van de Graaff accelerator. After irradiation, cells were kept in the
      dishes for either 1 or 48 h. The non-irradiated cells were then collected and
      assayed for both survival and mutation. When one side with cells was irradiated
      by alpha-particles (1, 10 and 100 Gy), the surviving fraction among the non
      irradiated cells was significantly lower than that of control after 48 h co
      culture. However, such a change was not detected after 1h co-culture or when
      medium alone was irradiated. Furthermore, co-cultivation with irradiated cells
      had no significant effect on the spontaneous mutagenic yield of non-irradiated
      cells collected from the other half of the double-mylar dishes. These results
      suggested that irradiated cells released certain cytotoxic factor(s) into the
      culture medium that killed the non-irradiated cells. However, such factor(s) had
      little effect on mutation induction. Our results suggest that different bystander
      end points may involve different mechanisms with different cell types.

PMID- 11827707
TI  - Ionising radiation and mutation induction at mouse minisatellite loci. The story
      of the two generations.
AB  - The analysis of the effects of ionising radiation on germline mutations is
      limited by the number of offspring that need to be analysed following exposure to
      a dose, which is relevant to risk assessment in humans. We have developed a new
      experimental approach using hypervariable mouse expanded simple tandem repeat
      (ESTR) loci (minisatellites) which are both highly sensitive to ionising
      radiation and which permit changes in mutation rates to be detected in relatively
      small samples. Here, we review the progress made in validating the model, and the
      unexpected features it has revealed, including a novel form of radiation-induced
      genetic instability that can be transmitted from one generation to the next.

PMID- 11827708
TI  - The radiation-induced lesions which trigger the bystander effect.
AB  - The ionizing radiation induced bystander effect is initiated by damage to a
      cellular molecule which then gives rise to a signal exported to other cells. The
      nature of this damage is considered with the understanding that it may not be the
      same as that responsible for the traditional cellular effects of radiation.
      Consideration is give to amounts of endogenous damage and to radiation yields of
      the various candidate lesions.

PMID- 11827709
TI  - Identification and cross-species comparisons of CYP2F subfamily genes in mammals.
AB  - The cytochrome P450 2F (CYP2F) subfamily genes are currently known only from cDNA
      sequences in human, mouse, rat and goat. Compared to other divisions of the CYP2
      gene family, the CYP2F subfamily is unusual in having few genes per species and
      in being selectively expressed in lung tissues. Sequencing genomic DNAs from
      human and gorilla has allowed us to determine the number of CYP2F subfamily loci
      in these species, the sources of known human transcripts, and the functional
      status of CYP2F loci in both primates. This information will make accurate
      genotyping of the functional and medically significant CYP2F1 gene possible in
      humans. Comparisons across multiple species show that the sequences of CYP2F
      subfamily genes are very conserved in mammals for intronic as well as exonic DNA.

PMID- 11827710
TI  - Pifithrin-alpha, an inhibitor of p53, enhances the genetic instability induced by
      etoposide (VP16) in human lymphoblastoid cells treated in vitro.
AB  - Recent studies indicate that p53-dependent apoptosis induced in normal tissues
      during chemo- and radiotherapy can cause severe side effects of anti-cancer
      treatments that limit their efficiency. The aim of the present work was to
      further characterise the role of p53 in maintaining genomic stability and to
      verify whether the inhibition of p53 function in normal cells by pifithrin-alpha
      (PFT-alpha) may contribute in reducing the side effects of cancer therapy. Two
      human lymphoblastoid cell lines, derived from the same donor, TK6 (p53 wild type)
      and WTK1 (p53 mutated) have been treated with an anti-neoplastic drug, the
      etoposide (VP16), an inhibitor of DNA topoisomerase II in presence or in absence
      of the p53 inhibitor PFT-alpha. Following treatments with VP16 on TK6 and WTK1,
      we observed a higher induction of chromosome aberrations in WTK1 (p53 mutated)
      and of apoptosis in TK6 (p53 wild-type) cells. The p53 inhibition by PFT-alpha in
      VP16 treated TK6 cells produced an increase of chromosomal aberrations and a
      reduction of apoptosis. Therefore, the temporary suppression of the function of
      p53 by PFT-alpha, increasing the survival of the normal cells, could be a
      promising approach to reduce the side-effects of cancer therapy but it is
      important to consider that the surviving cells could be genetically modified and
      consequently the risk of secondary tumours could be increased.

PMID- 11827711
TI  - Induction and decline of HPRT mutants and deletions following a low dose
      radiation exposure at Chernobyl.
AB  - This study was conducted to evaluate the ability of mutation in the hypoxanthine
      phosphoribosyltransferase gene (HPRT) to detect radiation-induced mutation in
      lymphocytes of Russian Chernobyl Clean-up workers, particularly as a function of
      time after exposure. It is part of a multi-endpoint study comparing HPRT mutation
      with chromosome translocation and glycophorin A mutation [Radiat. Res. 148 (1997)
      463], and extends an earlier report on HPRT [Mutat. Res. 431 (1999) 233] by
      including data from all 9 years of our study (versus the first 6 years) and
      analysis of deletion size. Blood samples were collected from 1991 to 1999. HPRT
      mutant frequency (MF) as determined by the cloning assay was elevated 16% in
      Clean-up workers (N=300, the entire group minus one outlier) compared to Russian
      Controls (N=124) when adjusted for age and smoking status (P=0.028). Since
      exposures occurred over a short relative to the long sampling period, the year of
      sampling corresponded roughly to the length of time since exposure (correlation
      coefficient=0.94). When date of blood sample was considered, Control MF was not
      time dependent. Clean-up worker MF was estimated to be 47% higher than Control MF
      in 1991 (P=0.004) and to decline 4.4% per year thereafter (P=0.03). A total of
      1123 Control mutants and 2799 Clean-up worker mutants were analyzed for deletion
      type and size by PCR assay for retention of HPRT exons and flanking markers on
      the X chromosome. There was little difference between the overall deletion
      spectra of Clean-up workers and Controls. However, there was a decline in the
      average size of deletions of Clean-up workers as time after exposure at Chernobyl
      increased from 6 to 13 years (P< or =0.05). The results illustrate the
      sensitivity of HPRT somatic mutation as a biomarker for populations with low dose
      radiation exposure, and the dependence of this sensitivity on time elapsed since
      radiation exposure.

PMID- 11827712
TI  - Bracken fern-induced malignant tumors in rats: absence of mutations in p53, H-ras
      and K-ras and no microsatellite instability.
AB  - Bracken fern (genus Pteridium) has been shown to induce tumors in domestic and
      experimental animals. Epidemiological studies have also shown an association
      between human exposure to bracken toxins and increased risk for the development
      of upper gastrointestinal tract tumors. Our aim in this study was to investigate
      possible genomic alterations in bracken fern-induced tumors of experimental
      animals searching for molecular markers that might be used for human
      epidemiological studies. Using human colorectal carcinogenesis as a molecular
      model, we examined eight malignant bracken fern-induced tumors of rats for
      mutations in the genes associated with the "classic pathway" of colorectal
      cancer, i.e. p53 and ras, and also in the "mutator pathway" by evaluating
      microsatellite instability. Exons 5-9 of the p53 gene and exons 1 and 2 of the K
      ras and H-ras genes were examined by DNA sequencing and no mutations were found
      in any of the eight tumors. Amplification of five previously validated
      microsatellite loci (one with mono-, three with di- and one with tetra-nucleotide
      repeat motifs) in the malignant tumors and in the surrounding normal tissue did
      not reveal any instability. The involvement of epigenetic alterations or of
      mutations in other tumor suppressor genes or oncogenes should be further
      investigated in the search for human epidemiological markers.

PMID- 11827714
TI  - Relative rates of insertion and deletion mutations in dinucleotide repeats of
      various lengths in mismatch repair proficient mouse and mismatch repair deficient
      human cells.
AB  - Microsatellites are DNA elements composed of short tandem repeats of 1-5bp. These
      sequences are particularly prone to frameshift mutation by insertion-deletion
      loop formation during replication. The mismatch repair system is responsible for
      correcting these replication errors, and microsatellite mutation rates are
      significantly elevated in the absence of mismatch repair. We have investigated
      the effect of varying the number of repeats in a (CA)n microsatellite on mutation
      rates in cultured mammalian cells proficient or deficient in mismatch repair. We
      have also compared the relative rates of single-repeat insertions and deletions
      in these cells. Two plasmid vectors were constructed for each repeat unit number
      (n=8, 17, and 30), such that the microsatellites, placed upstream of a bacterial
      neomycin resistance gene (neo), disrupted the reading frame of the gene in the (
      1) or (+1) direction. Plasmids were introduced separately into the cells, where
      they integrated into the cellular genome. Mutation rates were determined by
      selection of clones with frameshift mutations in the microsatellite that restored
      the reading frame of the neo gene. We found that mutation rates were
      significantly higher for (CA)17 and (CA)30 tracts than for (CA)8 tracts in both
      mismatch repair proficient (mouse) and deficient (human) cells. A mutational bias
      favoring insertions was generally observed. In both (CA)17 and (CA)30 tracts,
      single-repeat insertion rates were higher than single-repeat deletion rates with
      or without mismatch repair; deletions of multiple repeat units (> or =8bp) were
      observed in these tracts, where as deletions this large were not found in the
      (CA)8 tract. Single-repeat mutations of both types were made at similar rates in
      (CA)8 tracts in human mismatch repair deficient (MMR-) cells, but single-repeat
      insertion rates were higher than single-repeat deletion rates in mouse mismatch
      repair proficient (MMR+) cells. Results of these direct studies on microsatellite
      mutations in cultured cells should be useful for refinement of mathematical
      models for microsatellite evolution.

PMID- 11827713
TI  - Effects of biological DNA precursor pool asymmetry upon accuracy of DNA
      replication in vitro.
AB  - Deoxyguanosine triphosphate is underrepresented among the four common
      deoxyribonucleoside triphosphates (dNTPs), typically accounting for just 5-10% of
      the total dNTP pool. We have asked whether this pool asymmetry affects the
      fidelity of DNA replication, by use of an in vitro assay in which an M13 phagemid
      containing the Escherichia coli lacZalpha gene and an SV40 replication origin is
      replicated by extracts of human cells. By monitoring reversion of either a TGA or
      TAA codon within the lacZalpha gene, we found that replication in "biologically
      biased" dNTPs, representing our estimate of the concentrations in HeLa cell
      nuclei, is not significantly more accurate than when measured in reaction
      mixtures containing the four dNTPs at equimolar concentrations. However, sequence
      analysis of revertants revealed significantly different patterns of mispairing
      events leading to mutation. During replication at biased dNTP levels, mutations
      at the site 5' to C in the template strand for the TGA triplet were less frequent
      than seen in equimolar reaction mixtures, suggesting that extension from
      mismatches at this site is relatively slow, and proofreading efficiency high,
      when dGTP is the next nucleotide to be incorporated. Mismatches opposite template
      C, which might have been favored by the low physiological concentrations of dGTP,
      were not favored in our in vitro system, although one particular substitution at
      this site, TGA-->TTA, was strongly favored at low [dGTP]. An excess of one dNTP
      was found in our system to be more mutagenic than a corresponding deficiency. We
      also estimated dNTP concentrations in non-transformed human fibroblasts and found
      that in vitro replication at these levels caused significantly fewer mutations
      than we observed under equimolar conditions (100 microM each dNTP). This
      increased replication fidelity may result from increased proofreading efficiency
      at the lower dNTP levels; however, replication rates were decreased only slightly
      at these non-transformed fibroblast concentrations.

PMID- 11827716
TI  - Thermal decomposition of acetic anhydride-nitric acid mixtures.
AB  - The adoption of Ac2O/HNO3 mixtures for the nitration of organics or the
      preparation of nitric esters is not free from some risks of explosion. The
      behaviour of these mixtures at varying Ac2O/HNO3 molar ratios is studied by means
      of adiabatic and scanning calorimetry. A simplified kinetic model, based on two
      lumped reactions (one of which leads to the formation of tetranitromethane) is
      developed to simulate the thermal decomposition of the investigated system under
      adiabatic conditions. The use of this model allows satisfactory prediction of the
      temperature profiles in the reactor whereas calculated pressures are generally
      overestimated due to some model inadequacies to account for the absorption of
      gaseous decomposition products into the reacting solution.

PMID- 11827715
TI  - Aphidicolin induces 6-thioguanine resistant mutants in human diploid fibroblasts.
AB  - Cytotoxic and mutagenic effects of aphidicolin (APC), an inhibitor of DNA
      polymerases alpha and delta, were studied in human diploid VH-10 fibroblasts. The
      cells were treated (2 or 4h) with APC at concentration ranges of 10-40 microM.
      The effect of APC on cell survival after 4 h treatment was significantly higher
      than after 2 h treatment. The mutagenicity of APC was investigated at the HPRT
      locus, and the frequency of HPRT mutants was estimated by selection in medium
      containing 6-thioguanine (6-TG). Treatment of fibroblast cells with 20 microM of
      APC for 2 or 4 h resulted approximately in 5 or 10 times increase of 6-TG
      resistant mutant frequencies, respectively, compared to untreated control cells.
      The cell cycle analyses performed during the expression time (9-12 days) have
      shown that after 2 and 4h treatment with APC the cells were blocked in G2 phase
      during the majority of the expression period, compared to control cells. Four
      days after the treatment, the amount of cells in G2 phase increased about two
      fold (28.6-31.8% compared to 13.5% in the untreated cells). The mode of cell
      death during the expression time was via necrosis, rather than apoptosis, which
      was demonstrated by fluorescein-diacetate (FDA)-staining and terminal dUTP nick
      end labeling (TUNEL)-method.

PMID- 11827717
TI  - Hazard analysis of technologies for disposing explosive waste.
AB  - Hazards are identified for six different techniques for disposing decommissioned
      ammunition. Use has been made of functional modelling as a basis for hazard
      identification. Risk levels are estimated based on general accident rates in the
      chemical industry. The disposal techniques are "open burning" (OB), "open
      detonation" (OD), "closed detonation" (CD), "fluidised bed combustion" (FBC),
      "rotary kiln (RK) incineration", "mobile incineration". Closed detonation leads
      to most hazards and highest risk, followed by open burning and open detonation.
      The other three techniques are considerably safer. Risk due to transport is
      included in the analysis. Transport risk is not negligible for fluidised bed
      combustion and rotary kiln incineration at centrally located sites.

PMID- 11827718
TI  - Assessment of technologies for disposing explosive waste.
AB  - The environmental impact and safety aspects are assessed for six different
      techniques for disposing decommissioned ammunition. These are open burning and
      open detonation (OD), closed detonation (CD), fluidised bed combustion (FBC),
      rotary kiln (RK) Incineration, and Mobile furnace (MF) Incineration. The
      assessment is performed in the form of a multi-criteria decision analysis (MCDA).
      Objectives for minimising environmental impact and risk are defined to enable
      selection of the "best" technology. A framework for comparing emissions of
      different air pollutants is proposed. Environmental impacts are described,
      especially air pollutants. The environmental impacts of traditional OB and OD can
      be drastically reduced using controlled incineration techniques in combination
      with high-pressure water washout. This enables the explosive contents to be
      separated from the casing, and simultaneously the explosive is transformed to a
      desensitised water-based slurry.

PMID- 11827719
TI  - Catalytic combustion of carbon tetrachloride.
AB  - The catalytic combustion of carbon tetrachloride (CCl4) by metal oxide catalysts
      coated on the monolith support was investigated. The prepared catalysts were
      tested at temperatures between 300 and 800 degrees C and at varying gas hourly
      space velocity (GHSV) values with an excess air ratio of 3100%. The catalyst,
      whose composition was 18% Cr2O3, 2% Ce2O3 and 80% gamma-Al2O3, was found to
      almost completely oxidize CCl4. The operating conditions proposed are 5702 h(-1)
      for GHSV, 3100% excess air and a temperature slightly higher than 800 degrees C.
      The reaction rate expression was found to be independent of oxygen partial
      pressure but strongly dependent on CCl4 partial pressure.

PMID- 11827720
TI  - Prediction of leachate pH for cement paste containing pure metal compounds.
AB  - Neural network models, to predict the leachate pH for single batch extraction
      leaching tests conducted on Portland cement pastes containing pure compounds,
      were constructed using existing data from the literature. The models were able to
      represent the known non-linear dependency of pH on acid addition, and were used
      to show that Cu increases, and Zn and NO3- decrease, the leachate pH for addition
      of 8 meq acid/g dry cement (to achieve a mid-alkaline pH). Ba, Cd, Cr(III), Ni,
      Pb, Cl- and OH- had no detectable effect on the acid neutralisation capacity
      (ANC) of the cement pastes in the concentration ranges investigated. The
      laboratory where testing was conducted was found to be an important predictive
      variable, which acted as a surrogate variable for laboratory specific variables
      that were not adequately reported in the literature, such as cement
      characteristics, sample preparation details, and leaching test and pH measurement
      details. This work has shown that development of good empirical predictive models
      for solidified product leachate pH is feasible, and is limited only by the
      availability of data.

PMID- 11827721
TI  - Adsorptive removal of direct azo dye from aqueous phase onto coal based sorbents:
      a kinetic and mechanistic study.
AB  - This communication presents the results pertaining to the investigation conducted
      on color removal of trisazo direct dye, C.I. Direct Brown 1:1 by adsorption onto
      coal based sorbents viz. charfines, lignite coal, bituminous coal and comparing
      results with activated carbon (Filtrasorb-400). The kinetic sorption data
      indicated the sorption capacity of the different coal based sorbents. The
      sorption interaction of direct dye on to coal based sorbents obeys first-order
      irreversible rate equation and activated carbon fits with the first-order
      reversible rate equation. Intraparticle diffusion studies revealed the dye
      sorption interaction was complex and intraparticle diffusion was not only the
      rate limiting step. Isothermal data fit well with the rearranged Langmuir
      adsorption model. R(L) factor revealed the favorable nature of the isotherm of
      the dye-coal system. Neutral solution pH yielded maximum dye color removal.
      Desorption and interruption studies further indicated that the coal based
      sorbents facilitated chemisorption in the process of dye sorption while,
      activated carbon resulted in physisorption interaction.

PMID- 11827722
TI  - Treatment of high-strength phenolic wastewater by a new two-step method.
AB  - Treatment of high-strength phenolic wastewater by a novel two-step method was
      investigated in the present study. The two-step treatment method consisted of
      chemical coagulation of the wastewater by metal chloride followed by further
      phenol reduction by resin adsorption. The present combined treatment was found to
      be highly efficient in removing the phenol concentration from the aqueous
      solution and was proved capable of lowering the initial phenol concentration from
      over 10,000 mg/l to below direct discharge level (1mg/l). In the experimental
      tests, appropriate conditions were identified for optimum treatment operation.
      Theoretical investigations were also performed for batch equilibrium adsorption
      and column adsorption of phenol by macroreticular resin. The empirical Freundlich
      isotherm was found to represent well the equilibrium phenol adsorption. The
      column model with appropriately identified model parameters could accurately
      predict the breakthrough times.

PMID- 11827724
TI  - Antithrombotic and thrombolytic activities of Agkisacutacin, a snake venom
      proteinase, in experimental models.
AB  - The antithrombotic and thrombolytic activities of Agkisacutacin (Agk), a
      component isolated from Agkistrodon acutus, were determined in vitro and in vivo.
      The models employed included Chandler's model, arterio-venous shunt model and
      pulmonary embolus model. The effects of Agkisacutacin on coagulation, plasma
      fibrinogen and platelet aggregation induced by collagen, adenosine diphosphate
      (ADP) and thrombin were also investigated. The results showed that Agkisacutacin
      can significantly inhibit thrombus formation in Chandler's and arterio-venous
      shunt models, and accelerate thrombolysis of pulmonary emboli in rats. The data
      suggested that Agkisacutacin possessed antithrombotic and thrombolytic
      activities. Agkisacutacin was also partial characterized.

PMID- 11827725
TI  - Protective effect of allopurinol in the renal ischemia--reperfusion in
      uninephrectomized rats.
AB  - The effect of allopurinol (an inhibitor of xanthine oxidase) on oxidative stress,
      renal dysfunction, and histologic alterations was evaluated during the renal
      ischemia--reperfusion in uninephrectomized rats. Renal malondialdehyde and serum
      creatinine levels significantly increased after renal ischemia--reperfusion.
      However, the pretreatment with allopurinol demonstrated a protector effect in
      these parameters. Renal ischemia--reperfusion provoked a significant renal damage
      in the operated group. Tubular atrophy and interstitial fibrosis were attenuated
      by allopurinol when given prior to the surgery. In our study, allopurinol had a
      strong tendency to exert a beneficial effect during renal ischemia--reperfusion
      in uninephrectomized rats.

PMID- 11827726
TI  - Enhancement of hydralazine hypotension by low doses of isoniazid. Possible role
      of semicarbazide-sensitive amine oxidase inhibition.
AB  - The influence of pretreatment with 1 through 300 mg/kg ip of isoniazid (ISO) on
      blood pressure and heart rate responses to 0.1 mg/kg iv of hydralazine (HYD) was
      assessed in rats anesthetized with chloralose--urethane. HYD hypotension was
      significantly enhanced by ISO at doses between 3 and 300 mg/kg ip. Heart rate was
      not influenced by HYD in control or pretreated animals. Depressor responses to
      0.2 mg/kg iv of pinacidil (PIN) were also potentiated by ISO at 100 and 300, but
      not at 30 mg/kg. Similarly, ISO decreased cerebral gamma-aminobutyric acid (GABA)
      at the two highest doses; 30 mg/kg was without effect. Pretreatment of rats with
      ISO at 1 through 300 mg/kg failed to influence HYD-induced relaxation of aortic
      rings. These results were interpreted as indicating that potentiation of HYD
      hypotension by high doses of ISO is not specific for that vasodilator and is
      related to decreased cerebral GABA, as postulated previously. Lower doses could
      specifically potentiate the HYD-induced hypotensive effect by inhibition of
      semicarbazide-sensitive amine oxidase (SSAO), since both ISO and HYD are potent
      inhibitors of this enzyme. In support of this hypothesis, the SSAO inhibitors,
      benserazide (100 mg/kg ip) and mexiletine (50 mg/kg ip), were also found to
      enhance HYD hypotension.

PMID- 11827727
TI  - Pentoxifylline potentiates nitric oxide production in interleukin-1beta
      stimulated vascular smooth muscle cells through cyclic AMP-dependent protein
      kinase A pathway.
AB  - In the present study, we observed that pentoxifylline (PTX) significantly
      augmented the nitric oxide (NO) production and the iNOS gene expression by
      interleukin-1beta (IL-1beta)-stimulated vascular smooth muscle cells (VSMCs). The
      enhancing effects of PTX on the IL-1beta-induced NO production was associated
      with an increased intracellular cyclic AMP (cAMP) levels, and the synergistic
      effects of PTX on the IL-1beta-induced NO production was blocked by cAMP
      dependent protein kinase A (PKA) inhibitors. PKA inhibitors, KT5720 and H89,
      markedly decreased the augmented expression of iNOS gene whereas ODQ, a soluble
      guanylate cyclase inhibitor, did not affect the enhancing effect. In addition,
      the pretreatment with KT5720 or H89 abolished the increased translocation of the
      p65 subunit of NF-kappaB into the nucleus by PTX in the IL-1beta-stimulated
      VSMCs. These results suggest that enhancing effects of PTX on the iNOS gene
      expression in the IL-1beta-stimulated VSMCs is mediated predominantly through the
      activation of NF-kappaB via cAMP-dependent PKA pathway.

PMID- 11827728
TI  - Quantification of pulmonary capillary endothelium-bound angiotensin converting
      enzyme inhibition in man.
AB  - Angiotensin converting enzyme (ACE, kininase II) is an endothelial luminal
      ectoenzyme expressed abundantly on the pulmonary capillary endothelium and
      recognized as the site for the conversion of circulating angiotensin I to II. In
      the present study, we have applied recently developed methodologies for assaying
      pulmonary capillary endothelium-bound (PCEB) ACE activity in man, to estimate the
      interaction of an ACE inhibitor (enalaprilat) with PCEB ACE in human subjects.
      Trace amounts of the specific ACE substrate, 3H-benzoyl-Phe-Ala-Pro (3H-BPAP; 40
      Ci or 2 nmol), was injected as a bolus into the subclavian vein and immediately
      blood was withdrawn from a radial arterial catheter. Plasma concentrations of
      surviving substrate and product (3H-benzoyl-Phe) were estimated and BPAP
      utilization was calculated during a single transpulmonary passage, at baseline
      (T(0)) and at 15 min (T(15)) and 2 h (T(120)) after intravenous administration of
      1.5 g/kg enalaprilat in 12 normotensive subjects. This treatment had no
      significant effect on mean arterial pressure (91+/- 6 vs. 84 +/- 7 vs. 88 +/- 6
      mm Hg for T(0), T(15) and T(120), respectively), but significantly decreased
      serum and PCEB ACE activities. When normalized to predrug (T(0)) activity levels,
      enalaprilat inhibited PCEB and serum ACE activities at T(15) 74 +/- 6% and 68 +/-
      6%, respectively. However, 2 h after enalaprilat (T(120)), PCEB ACE inhibition
      was maintained at 66 +/- 7%, whereas serum ACE inhibition was reduced to 46 +/-
      8% (P<.01 from PCEB ACE), suggesting a preferential PCEB ACE inhibitory effect of
      enalaprilat.

PMID- 11827730
TI  - Behavioral neurogenetics, the genetic dissection of brain and behavior.
      Proceeding of meetings of the International Behavioural and Neural Genetics
      Society. 1999-2001.

PMID- 11827729
TI  - Influences of nonselective, beta(1)-selective and vasodilatory beta(1)-selective
      beta-blockers on arterial pulse wave velocity in normotensive subjects.
AB  - beta-Adrenoceptor blockers with disparate properties may have differential
      influences on arterial pulse wave velocity (PWV). Therefore, influences of single
      medium doses of bisoprolol, propranolol and celiprolol on PWV were compared in
      healthy subjects. Arterial PWV was obtained from the time delay between flow
      pulses measured from the root of the aorta and the popliteal artery. Bisoprolol
      and propranolol decreased arterial PWV more than placebo (P less-than-or-equal to
      .002) and celiprolol (P<.0001). In conclusion, the acute effects of bisoprolol
      and propranolol on arterial PWV in normotensive subjects seem to differ from that
      of celiprolol.

PMID- 11827731
TI  - Hippocampal dysfunction and behavioral deficit in the water maze in mice: an
      unresolved issue?
AB  - Dysfunction of the hippocampal formation manifests as impaired relational
      learning and memory in humans and animals. One of the most frequently applied
      relational learning paradigms in animals is the Morris water maze (MWM), in which
      the subject is required to learn complex spatial relationships of visual cues.
      MWM has been employed as a diagnostic tool to investigate effects of drugs and
      mutations. However, the validity of this test and its ability to properly detect
      hippocampal dysfunction have been questioned. In order to corroborate the role of
      hippocampus in spatial learning, we employed ibotenic acid lesioning and ablated
      the hippocampus bilaterally or unilaterally in mice, as ascertained by magnetic
      resonance imaging. We found a significant impairment in response to hippocampal
      disruption that was more pronounced in mice with bilateral lesion than with
      unilateral lesion. However, the results also indicated that even the mice with
      bilateral lesion could improve their performance, which confirms the notion that
      the MWM has an important non-hippocampal component. It is thus possible that
      experimental alteration of brain function does not manifest as modified
      performance in MWM, even when hippocampal function is modified (false-negative
      finding), or manifest as altered performance without varying hippocampal function
      (false-positive finding), possibilities that have important implications for
      studies using genetic and pharmacological manipulation of the brain.

PMID- 11827732
TI  - Chronic inhibition of glutamine synthetase is not associated with impairment of
      learning and memory in mice.
AB  - The convulsant methionine sulfoximine (MSO) is a byproduct of the agenized flour
      commonly used for feeding domestic animals decades ago. MSO is a powerful
      glycogenic and epileptogenic agent, and it is an irreversible inhibitor of
      glutamine synthetase. This latter effect was hypothesized to be responsible for
      the increase in the incidence of some neuropathologies in humans, such as
      Alzheimer's disease or Parkinson's disease. In order to test this hypothesis, we
      chronically administered MSO to two inbred strains of mice, C57BL/6J and BALB/cJ,
      and analyzed possible alterations in learning and memory features of these mice.
      Mice were given 20 mg/kg of MSO three times a week for 10 weeks. Spatial learning
      capabilities assessed with a radial maze were not affected by the long-term MSO
      treatment, although activity was significantly decreased in BALB/cJ mice. Thus,
      our data suggest that long-term administration of non-convulsive and non
      glycogenic doses of MSO do not alter the spatial memory of mice. Our results do
      not support the hypothesis that chronic treatment with MSO influences hippocampus
      dependent learning abilities in mice.

PMID- 11827733
TI  - Learned fear, emotional reactivity and fear of heights: a factor analytic map
      from a large F(2) intercross of Roman rat strains.
AB  - Anxiety-related behaviours were evaluated across various tests in a 800 F(2)
      intercross of the Roman high- and low-avoidance inbred rats. These tests either
      evoke unlearned (open field [OF]; plus-maze [PM]; hole-board [HB]; spontaneous
      activity [A]; and acoustic startle reflex [ASR]) or learned (classical fear
      conditioning [CFC]; and shuttlebox avoidance conditioning [SAC]), anxious/fearful
      responses. Using factor analysis (oblique rotation), we obtained a six-fold
      solution with 14 variables derived from all tests. These six factors represented
      SAC, CFC, PM anxiety, PM and OF activity, ASR anxiety, plus a mixed whole of
      anxious and activity variables (from OF and A), respectively. In searching for a
      smaller number of meaningful factors, we applied a three-factor solution that
      coherently corresponded with differentiated facets of fearfulness, rather than
      with the tests. Results showed that (1) measures of SAC and CFC strongly loaded
      onto Factor 1, labelled as "Learned Fear"; (2) a blend of almost all variables
      loaded onto Factor 2, called "Emotional Reactivity"; and (3) open arm behaviour
      in the PM loaded onto Factor 3, called "Fear of Heights." After discussing
      limitations of this apparently consistent behavioural map of anxiety, we advance
      some connections between those factors with quantitative trait loci candidates
      (genetic markers) as detected in the same sample.

PMID- 11827734
TI  - Wheel running behavior is impaired by both surgical section and genetic absence
      of the mouse corpus callosum.
AB  - Mice lacking a corpus callosum (CC) often show little or no deficit on tests of
      behavior. This paper reports that on highly complex bimanual motor tasks,
      deficits can be found. The speed of running on a wheel with irregularly spaced
      rungs is reduced by both hereditary absence of the CC in 129 x BALB/c recombinant
      mice and surgical section of the CC in genetically normal B6D2F(2) mice. The
      effect of CC absence appears on measures most closely related to speed, no
      influence exists on the amount of running over a period of 5 days. Motor behavior
      on a notched balance beam, on the other hand, shows clear superiority of the
      hybrid mice but no relation with reduced size of the CC, whether it was produced
      by genotype or surgery. The effect of absent CC is task dependent, but it is not
      obscured by developmental compensation in the recombinant mice.

PMID- 11827735
TI  - The strain-specific involvement of nucleus accumbens in latent inhibition might
      depend on differences in processing configural- and cue-based information between
      C57BL/6 and DBA mice.
AB  - Latent inhibition (LI) consists of decreased associative strength between an
      elemental stimulus (CS: tone) paired with an unconditioned stimulus (US:
      footshock) following non-reinforced pre-exposure to the tone. In view of the
      differences shown by C57BL/6 (C57) and DBA/2 (DBA) mice in processing elemental
      vs. configural stimuli, the present experiments were designed (1) to assess
      whether these differences were likely to interfere with the capability of each
      strain to show LI, and (2) to verify the extent to which lesions of the nucleus
      accumbens, which have been reported to enhance attention towards contextual
      stimuli under certain conditions, might interfere with the development of LI. C57
      and DBA mice with Nacc or sham lesions were given two periods (4 or 7 days) of
      pre-exposure to a CS (tone) then subjected to two CS-US pairings given on a
      single day. On the day after, freezing to the tone was examined in each group.
      Results show that, following the shorter period of pre-exposure, LI developed in
      sham-lesioned DBA but did not in sham-lesioned C57. Nacc lesions, however, were
      found (1) to block LI in DBA but (2) to promote LI in C57. After the longer
      period of pre-exposure LI was observed in both strain and lesion conditions. In
      general, these results confirm that strain differences in processing the tone as
      a single elemental cue (DBA) or, alternatively, as a part of a contextual
      configural stimulus (C57) can interfere with the development of LI. In addition,
      they indicate that Nacc lesions, that are susceptible to increase attention to
      the background, might modify the salience of the tone and produce opposite effect
      on LI according to the strain specialisation to show elemental or configural
      responding.

PMID- 11827736
TI  - Behavioral and neuroanatomical characterization of FVB/N inbred mice.
AB  - The inbred strain FVB/N is becoming increasingly popular to generate transgenic
      animals. We compared animals from this strain with well-characterized C57BL/6J
      animals on four different behavioral tests: the elevated plus maze test of
      anxiety, a standard opponent aggression test, the open-field test, and spatial
      learning in a radial maze. Our results indicate that FVB/N animals have slightly
      higher levels of anxiety and aggression, are hyperactive, and have a clear
      learning deficit. The latter finding seems to be related to an exceptionally
      small intrapyramidal and infrapyramidal mossy fiber projection. It is recommended
      that transgenic experiments employing this strain use F1 crosses between FVB/N
      and C57BL/6J as much as possible for behavioral experiments intended to evaluate
      spatial learning.

PMID- 11827738
TI  - Genetic basis of anxiety-like behaviour: a critical review.
AB  - The way genetic and/or environmental factors influence psychiatric disorders is
      an enduring question in the field of human psychiatric diseases. Anxiety-related
      disorders provide a relevant example of how such an interaction is involved in
      the aetiology of a psychiatric disease. In this paper we review the literature on
      that subject, reporting data derived from human and rodent studies. We present in
      a critical way the animal models used in the studies aimed at investigating the
      genetic basis of anxiety, including inbred mice, selected lines, multiple marker
      strains, or knockout mice and review data reporting environmental components
      influencing anxiety-related behaviours. We conclude that anxiety is a complex
      behaviour, underlined not only by genetic or environmental factors but also by
      multiple interactions between these two factors.

PMID- 11827737
TI  - Genetic diversity underlying capsaicin intake in the Mishima battery of mouse
      strains.
AB  - Capsaicin is the active substance responsible for the pungent sensation produced
      by red pepper. In order to approach the underlying genetic mechanism for
      preference of red pepper, we conducted a 12-h, 1-bottle intake test of capsaicin
      solution using both male and female animals from the Mishima battery of mouse
      strains: 10 wild-derived inbred strains (PGN2, BFM/2, HMI, CAST/Ei, NJL, BLG2,
      CHD, SWN, KJR, MSM), 1 strain derived from the so-called fancy mouse (JF1), and 3
      widely used laboratory strains (C57BL/6J, DBA/1J and BALB/cAnN). The
      concentration of capsaicin was increased from 0.5 to 15 microM successively.
      Gender differences were not observed in this test, but we found striking strain
      differences in capsaicin intake. Relative to baseline water intake, C57BL/6J and
      DBA/1J consumed 10%, whereas two wild strains, KJR and MSM, ingested
      approximately 60% of the 15-microM capsaicin solution. In a 2-bottle fluid
      preference test, both C57BL/6J and MSM strains reject capsaicin fluid even at the
      0.5-microM concentration, which indicates that the receptors for capsaicin in
      these strains recognize capsaicin at a similar level. Thus, the strain
      differences at higher capsaicin concentrations in the 1-bottle test may reflect
      differences in central nervous system response to the capsaicin solution. The
      genetic difference in intake of capsaicin observed in these strains may provide a
      useful tool for identifying genes underlying response to red pepper in mice and
      other mammalian species.

PMID- 11827739
TI  - Corticosteroid receptors in the brain: gene targeting studies.
AB  - Corticosteroids are released by the adrenal cortex with a diurnal rhythm and in
      response to stressful environmental changes. They not only act on peripheral
      organs, but also regulate brain physiology, thereby affecting mental processes
      like emotion and cognition. Here, we discuss the role of the two known
      corticosteroid receptors--glucocorticoid receptor (GR) and mineralocorticoid
      receptor (MR)--in the brain by summarizing the results obtained with various
      genetically modified mouse lines. In these lines, either the GR or the MR gene
      has been targeted or GR protein levels have been upregulated or downregulated.
      Analysis of the different lines confirms the importance of GR in the regulation
      of the hypothalamic pituitary adrenal (HPA) axis because interference with GR
      activity activates the HPA axis, whereas increased GR protein levels inhibit HPA
      axis activity. Genetic downregulation of GR protein levels and inactivation of
      the GR gene in the brain reduce anxiety-related behavior, which reveals a central
      role of GR in emotional behavior. Both HPA axis activity and anxiety are
      modulated by corticotropin releasing hormone (CRH); therefore, we include in the
      discussion results obtained with genetically modified CRH or CRH receptor mice.
      We further address the important role of corticosteroid receptors for hippocampal
      function and integrity. Cellular properties of CA1 neurons are changed, and
      hippocampal-dependent explicit memory is affected in GR mutant animals. Comparing
      MR and GR mutant animals suggests the requirement of MR but not GR for dentate
      gyrus granule cell maintenance. Because an imbalance in glucocorticoid levels is
      associated with cognitive impairments and mental disorders, the described mouse
      lines will aid in understanding the mechanisms involved in the pathology of these
      disorders.

PMID- 11827740
TI  - To die or not to die, does it change the function? Behavior of transgenic mice
      reveals a role for developmental cell death.
AB  - In humans, perturbations in the developmental neuronal death leading to an excess
      of neurons could be associated with developmental neuropsychiatric disorders. Hu
      bcl-2 transgenic mice appear to be a valuable tool to study the functional role
      of developmental programmed cell death. Indeed, the over-expression of the anti
      apoptotic gene bcl-2 decreases developmental neuronal death and Hu-bcl-2 mice
      present supernumerary neurons in several brain regions. A detailed behavioral
      analysis of these mice revealed selective deficits. Hu-bcl-2 mice have normal
      vision, general activity and motor skills. Only the most complex behavior like
      anxiety and learning abilities are impaired in these mice.

PMID- 11827741
TI  - 5-HT(1B) receptor knockout mice show no adaptive changes in 5-HT(1A) receptor
      function as measured telemetrically on body temperature and heart rate responses.
AB  - Two presynaptic receptors play an important role in the regulation of
      serotonergic neurotransmission, i.e., the 5-HT(1A) and 5-HT(1B) receptor. The
      present study focuses on putative adaptive changes in the 5-HT(1A) receptor
      system in mice that lack 5-HT(1B) receptors (5-HT(1B) KO). 5-HT(1A) receptor
      sensitivity was assessed in vivo in two models of presynaptic 5-HT(1A) receptor
      activity: agonist-induced hypothermia and prevention of stress-induced
      hyperthermia. The effects of 5-HT(1A) receptor activation by flesinoxan (0.1-3.0
      mg/kg s.c.) were determined telemetrically on body temperature and heart rate in
      5-HT(1B) KO and wild-type (WT) mice. Flesinoxan induced hypothermia dose
      dependently without affecting heart rate and prevented stress-induced
      hyperthermia and tachycardia equipotently in both genotypes. Specificity of these
      responses was confirmed by blockade with the selective 5-HT(1A) receptor
      antagonist WAY100635 (1.0 mg/kg s.c.). The importance of continuous sampling in
      freely moving subjects to improve appropriate characterization of mutants is
      discussed. 5-HT(1B) KO mice showed no shift in 5-HT(1A) receptor sensitivity
      compared to WT mice. This study found no indications for adaptive changes in
      presynaptic 5-HT(1A) receptor function in 5-HT(1B) KO mice as measured
      telemetrically on body temperature and heart rate responses.

PMID- 11827742
TI  - Reappraisal of the serotonin 5-HT(1B) receptor gene in alcoholism: of mice and
      men.
AB  - Because pharmacological and genetic data supported the idea that serotonin
      receptors of the 5-HT(1B) type can play a modulatory role in alcohol consumption
      in both human and rodents, the 5-HT(1B) receptor gene is considered as a
      candidate gene for alcohol dependence. However, contradictory results have been
      reported as a positive association between alcohol dependence, and either the
      861C or the 861G allele of the G861C polymorphism of the 5-HT(1B) receptor gene
      can be found in the literature. Further investigations in a population of 136
      male alcoholics compared with 72 male control subjects demonstrated that none of
      these alleles was actually associated with alcohol dependence. In addition, in
      contrast with previous results of the literature, ethanol intake under free
      choice conditions (i.e., ethanol solution vs. water) was found to be similar in 5
      HT(1B)-/- knock mice and paired wild-type controls. The 5-HT(1B) receptor gene
      may thus not be a key component in the genetic background underlying alcohol
      dependence in human and alcohol preference in rodents, although these results
      should be considered as preliminary according to the small size of our sample.

PMID- 11827743
TI  - Molecular genetics and animal models in autistic disorder.
AB  - Autistic disorder is a behavioural syndrome beginning before the age of 3 years
      and lasting over the whole lifetime. It is characterised by impaired
      communication, impaired social interactions, and repetitive interests and
      behaviour. The prevalence is about 7/10,000 taking a restrictive definition and
      more than 1/500 with a broader definition, including all the pervasive
      developmental disorders. The importance of genetic factors has been highlighted
      by epidemiological studies showing that autistic disorder is one of the most
      genetic neuropsychiatric diseases. The relative risk of first relatives is about
      100-fold higher than the risk in the normal population and the concordance in
      monozygotic twin is about 60%. Different strategies have been applied on the
      track of susceptibility genes. The systematic search of linked loci led to
      contradictory results, in part due to the heterogeneity of the clinical
      definitions, to the differences in the DNA markers, and to the different methods
      of analysis used. An oversimplification of the inferred model is probably also
      cause of our disappointment. More work is necessary to give a clearer picture.
      One region emerges more frequently: the long arm of chromosome 7. Several
      candidate genes have been studied and some gave indications of association: the
      Reelin gene and the Wnt2 gene. Cytogenetical abnormalities are frequent at 15q11
      13, the region of the Angelman and Prader-Willi syndrome. Imprinting plays an
      important role in this region, no candidate gene has been identified in autism.
      Biochemical abnormalities have been found in the serotonin system. Association
      and linkage studies gave no consistent results with some serotonin receptors and
      in the transporter, although it seems interesting to go further in the
      biochemical characterisation of the serotonin transporter activity, particularly
      in platelets, easily accessible. Two monogenic diseases have been associated with
      autistic disorder: tuberous sclerosis and fragile X. A better knowledge of the
      pathophysiology of these disorders can help to understand autism. Different other
      candidate genes have been tested, positive results await replications in other
      samples. Animal models have been developed, generally by knocking out the
      different candidate genes. Behaviour studies have mainly focused on anxiety and
      learning paradigms. Another group of models results from surgical or toxic
      lesions of candidate regions in the brain, in general during development. The
      tools to analyse these animals are not yet standardised, and an important effort
      needs to be undertaken.

PMID- 11827744
TI  - Glia in development, function, and neurodegeneration of the adult insect brain.
AB  - Glial cells have long been viewed as a passive framework for neurons but in the
      meanwhile were shown to play a much more active role in brain function and
      development. Several reviews have described the function of glia in the insect
      embryo. The focus of this review is the role of glial cells in the development
      and function of the normal and diseased adult brain. In different insect species,
      a considerable variety of central nervous system glia has been described
      indicating adaptation to different functional requirements. In the development of
      the adult visual and olfactory system, glial cells guide incoming axons acting as
      intermediate targets. Glia are part of the insect blood-brain barrier, provide
      nourishment for neurons, and help to regulate the extracellular concentration of
      ions and neurotransmitters. To fulfill these tasks insect glial cells, like
      vertebrate glia, interact with each other and with neurons, thus influencing
      neural activity. The examples presented suggest that crosstalk between all brain
      cells is necessary not only to develop and maintain the complex insect brain but
      also to endow it with the capacity to respond and adapt to the changing
      environment.

PMID- 11827745
TI  - Oxidation of tetrahydrobiopterin by biological radicals and scavenging of the
      trihydrobiopterin radical by ascorbate.
AB  - One-electron oxidation of (6R)-5,6,7,8-tetrahydrobiopterin (H(4)B) by the azide
      radical generates the radical cation (H(4)B(*)(+)) which rapidly deprotonates at
      physiological pH to give the neutral trihydrobiopterin radical (H(3)B(*)); pK(a)
      (H(4)B(*)(+) <==> H(3)B(*) + H(+)) = (5.2 +/- 0.1). In the absence of ascorbate
      both the H(4)B(*)(+) and H(3)B(*) radicals undergo disproportionation to form
      quinonoid dihydrobiopterin (qH(2)B) and the parent H(4)B with rate constants
      k(H(4)B(*)(+) + H(4)B(*)(+)) = 6.5 x 10(3) M(-1) s(-1) and k(H(3)B(*) + H(3)B(*))
      = 9.3 x 10(4) M(-1) s(-1), respectively. The H(3)B(*) radical is scavenged by
      ascorbate (AscH(-)) with an estimated rate constant of k(H(3)B(*) + AscH(-))
      similar 1.7 x 10(5) M(-1) s(-1). At physiological pH the pterin rapidly scavenges
      a range of biological oxidants often associated with cellular oxidative stress
      and nitric oxide synthase (NOS) dysfunction including hydroxyl ((*)OH), nitrogen
      dioxide (NO(2)(*)), glutathione thiyl (GS(*)), and carbonate (CO(3)(*-))
      radicals. Without exception these radicals react appreciably faster with H(4)B
      than with AscH(-) with k(*OH + H(4)B) = 8.8 x 10(9) M(-1) s(-1), k(NO(2)(*) +
      H(4)B) = 9.4 x 10(8) M(-1) s(-1), k(CO(3)(*-) + H(4)B) = 4.6 x 10(9) M(-1) s(-1),
      and k(GS(*) + H(4)B) = 1.1 x 10(9) M(-1) s(-1), respectively. The glutathione
      disulfide radical anion (GSSG(*-)) rapidly reduces the pterin to the
      tetrahydrobiopterin radical anion (H(4)B(*-)) with a rate constant of k(GSSG(*-)
      + H(4)B) similar 4.5 x 10(8) M(-1) s(-1). The results are discussed in the
      context of the general antioxidant properties of the pterin and the redox role
      played by H(4)B in NOS catalysis.

PMID- 11827746
TI  - Radiation sensitivity depends on OGG1 activity status in human leukemia cell
      lines.
AB  - To assess the role of 8-oxoguanine glycosylase (OGG1) in the cell defense against
      radiation injury, the radiation-induced cytotoxicities were compared between the
      mutant type KG-1 featuring a loss of OGG1 activity due to a homozygous mutation
      of Arg 229 Gln, and the wild type U937. While the following three obvious
      toxicities were displayed in KG-1, they were observed only minimally in U937.
      These were: a dramatic arrest at the G2/M phase indicated by a marked increase in
      both the number of G2/M cells and the expression of cyclin B1, cdc2, and mitotic
      phosphoprotein monoclonal-2 (MPM-2)-reactive proteins; a severe apoptosis shown
      by a marked increase in the number of cells with hypo-diploid DNA and DNA
      fragmentation; and as a result, a severe inhibition of cell growth and
      proliferation measured by the MTT test and [(3)H]-thymidine uptake assay. As
      expected, KG-1 exhibited a significant increase in the 8-hydroxyguanine level in
      DNA whereas U937 did not. However, the level of irradiation-induced lipid
      peroxidation was almost the same in both cell lines. All of these symptoms shown
      by KG-1 were observed in Molt-4 and CEM-CM3, which were also found to feature low
      OGG1 activity. These findings suggest that OGG1 plays an important role in cell
      survival from radiation-induced damage and are also indicative of the capability
      of 8-hydroxyguanine in DNA to induce cellular toxicities.

PMID- 11827748
TI  - Detection and removal of contaminating hydroxylamines from the spin trap DEPMPO,
      and re-evaluation of its use to indicate nitrone radical cation formation and
      S(N)1 reactions.
AB  - A previous report that the spin trap 5-diethoxyphosphoryl-5-methyl-1-pyrroline-N
      oxide (DEPMPO) allows DEPMPO radical cation formation to be detected via the
      production of a carbon-centred radical adduct (assigned as the cis-hydroxyethyl
      species, formed by an intramolecular process) is shown to be incorrect. Rather,
      this and other paramagnetic species arise from the facile oxidation of trace
      hydroxylamine impurities present in commercial DEPMPO samples. As a result,
      techniques for the detection and elimination of such hydroxylamine impurities
      from DEPMPO solutions were developed and are described; these should prove to be
      of general use in EPR spin trapping experiments.

PMID- 11827747
TI  - A cross talk between cellular signalling and cellular redox state during heat
      induced apoptosis in a rat histiocytoma.
AB  - Increasing evidence provides support for oxidative stress to be closely linked to
      apoptosis. Reactive oxygen species (ROS) are thought to be involved in many forms
      of programmed cell death. Though heat shock is a universal phenomenon, BC-8, a
      macrophage-like cell line failed to mount a typical heat shock response. In the
      absence of heat shock proteins and functional p53, BC-8 cells undergo apoptosis
      through CD95 signaling. In the present study, we have investigated the role of
      ROS in the regulation of apoptosis in these cells. We show that cells transfected
      with hsp70 and functional p53 are resistant to heat-induced apoptosis through
      inhibition of CD95 expression and ROS induction. Furthermore, apoptosis in BC-8
      cells resulted in two bursts of ROS generation, one correlated with heat stress
      and intracellular depletion of GSH and the other with Bax overexpression and
      cytochrome c release. Antioxidants could not protect these cells from heat
      induced apoptosis and the death pathway seems to be dependent on initial
      signaling cascade subsequently altering the intracellular redox. Hence, our data
      suggest that ROS generation in BC-8 cells upon heat shock is facultative but not
      obligatory for apoptosis.

PMID- 11827749
TI  - Synergistic effect of 4-hydroxynonenal and PPAR ligands in controlling human
      leukemic cell growth and differentiation.
AB  - Peroxisome proliferator-activated receptors play an important role in the
      differentiation of different cell lines. In this study we demonstrate that PPAR
      alpha ligands (clofibrate and ciprofibrate) and PPAR-gamma ligands (troglitazone
      and 15d-prostaglandin J2) inhibit growth and induce monocytic differentiation in
      HL-60 cells, whereas only PPAR-gamma ligands inhibit growth of U937 cells.
      Differentiation was demonstrated by the analysis of surface antigen expression
      CD11b and CD14, and by the characteristic morphological changes. PPAR-gamma
      ligands are more effective than PPAR-alpha ligands in the inhibition of cell
      growth and in the induction of differentiation. The physiological product of
      lipid peroxidation, 4-hydroxynonenal (HNE), which alone induces granulocytic-like
      differentiation of HL-60 cells, potentiates the monocytic differentiation induced
      by ciprofibrate, troglitazone, and 15d-prostaglandin J2. The same HNE treatment
      significantly inhibits U937 cell growth and potentiates the inhibition of cell
      growth in PPAR-gamma ligand-treated cells. However, HNE does not induce a
      significant number of CD14-positive U937 cells. HNE causes a great increase of
      PPAR-gamma expression in both HL-60 and U937 cells, whereas it does not modify
      the PPAR-alpha expression. This observation may account for the high synergistic
      effect displayed by HNE and PPAR-gamma ligands in the inhibition of cell growth
      and differentiation induction. These results represent the first evidence of the
      involvement of a product of lipid peroxidation in the modulation of PPAR ligand
      activity and suggest a relationship between HNE and PPAR ligand pathways in
      leukemic cell growth and differentiation.

PMID- 11827750
TI  - Rapid mtDNA deletion by oxidants in rat liver mitochondria after hemin exposure.
AB  - The amounts of superoxide and hydrogen peroxide generated by mitochondria under
      physiological conditions can be enhanced by cellular stress. This study tested
      the hypothesis that the response to hemin-induced stress, which includes heme
      oxygenase-1 (HO-1) induction, predisposes to oxidative damage of mitochondrial
      DNA (mtDNA). Hepatic mitochondria from control, hemin-, and CO-exposed rats were
      incubated with tert-butyl hydroperoxide (tert-BH) or the NO donor 1,2,3,4
      oxatriazolium, 5-amino-3- (3,4-dichlorophenyl)-chloride (GEA 3162). Mitochondrial
      total and oxidized glutathione (GSH and GSSG), total and free iron, and 8-oxo-7,
      8-dihydro-2' deoxyguanosine (8-OHdG) were determined with and without oxidants.
      As expected, oxidation by tert-BH induced significant GSH depletion and increased
      amounts of free iron and 8-OhdG. Oxidant exposure rapidly produced a large mtDNA
      deletion involving the coding regions for cytochrome c oxidase (COX 1) and NADH
      dehydrogenase (ND1 and ND2). Hemin and CO greatly exacerbated susceptibility to
      the deletion of mtDNA by tert-BH, and this was attenuated by preincubation with
      GSH methyl ester. Analysis of mitochondria-associated proteins Bax and Bcl-xl in
      hemin- and CO-exposed rats showed significant responses, revealing interactions
      with apoptotic pathways. Thus, hemin-induced mitochondrial events sensitize a
      specific region of the mitochondrial genome to deletion, which is related to
      depletion of GSH and is not explained by effects of CO. This mtDNA damage is
      associated with altered expression of mitochondrial cell death proteins, thereby
      suggesting a novel mechanism for systemic or environmental pro-oxidants to
      influence apoptosis.

PMID- 11827751
TI  - Effects of ambient oxygen concentration on the growth and antioxidant defenses of
      of human cell cultures established from fetal and postnatal skin.
AB  - Oxygen toxicity is believed to arise from changes in the rates at which cells
      generate reactive oxygen species (ROS). Sensitivity to hyperoxia has been
      postulated to depend on levels of antioxidant defense. Human cells obtained from
      fetal tissues have lower antioxidant defenses than those obtained from adult
      tissue. The present study was performed to determine whether the differences in
      fetal and adult antioxidant defense levels modulated their responses to changes
      in the ambient oxygen concentration. Our results demonstrate that oxygen
      modulates the proliferation of human fetal and adult skin fibroblasts in a
      similar fashion. In general, skin fibroblasts grew better at approximately 31 mm
      Hg, regardless of donor age. Manganese superoxide dismutase, catalase, and
      glutathione peroxidase activities were lower in fetal cells than in adult
      fibroblasts. Copper/zinc superoxide dismutase and glucose-6-phosphate
      dehydrogenase were similar in fetal and postnatal tissues and were unaltered
      appreciably by hyperoxic exposure. Glutathione concentration increased at higher
      oxygen tensions; however, the increase was much greater in fetal cells than in
      cultures derived from adult skin. These observations demonstrate that the
      capacity of fetal and adult cells to cope with oxidative stress, while similar,
      result from distinct mechanisms.

PMID- 11827752
TI  - Characterization of the differentiated antioxidant profile of human saliva.
AB  - Saliva is armed with various defense mechanisms, such as the immunological and
      enzymatic defense systems. In addition, saliva has the ability to protect the
      mucosa against mechanical insults and to promote its healing via the activity of
      epidermal growth factor. However, another defense mechanism, the antioxidant
      system, exists in saliva and seems to be of paramount importance. The most
      interesting finding of the present study was the demonstration of the existence
      of much higher concentrations of the various salivary molecular and enzymatic
      antioxidant parameters in the parotid saliva compared with the
      submandibular/sublingual saliva. For example, peroxidase, superoxide dismutase,
      uric acid, and total antioxidant status were higher in resting parotid saliva
      compared with resting submandibular/sublingual saliva by 2405, 235, 245, and
      147%, respectively. Another important finding was the distinction between the
      salivary antioxidant system and the immunological and enzymatic protective
      systems, as represented by the salivary concentrations of secretory IgA and
      lysozyme, respectively. These findings suggest that the profound antioxidant
      capacity of saliva secreted from parotid glands is related either to the
      different physiological demands related to eating (parotid predominance), to oral
      integrity maintenance (submandibular/sublingual predominance), or to the high
      content of deleterious redox-active transitional metal ions present in parotid
      saliva. This also may signify that our oral cavity environment is only partially
      protected against oxidative stress during most of the day and night.

PMID- 11827753
TI  - Regulation of mitochondrial thioredoxin peroxidase I expression by two different
      pathways: one dependent on cAMP and the other on heme.
AB  - Mitochondrial isoform of thioredoxin peroxidase (mTPx I) is an antioxidant
      protein recently described in Saccharomyces cerevisiae. Here we characterized
      pathways that lead to mTPx I induction in two situations: growth in media
      containing low glucose concentrations and treatment with peroxides. The induction
      of mTPx I by growth on low glucose concentrations was dependent on cAMP and on
      the transcription factors Msn2p/Msn4p as demonstrated by northern blot
      experiments using yeast strains with deletion of MSN2 and MSN4 genes and also
      using a strain permeable to cAMP. mTPx I expression was also induced by peroxides
      in a time- and dose-dependent manner and varied with the carbon source present in
      the media. Deletion of HAP1 or inhibition of heme synthesis abolished induction
      of mTPx I by H(2)O(2) on cells which were grown in media containing glucose,
      indicating that Hap1p is involved in the regulation of this process. mTPx I was
      induced by H(2)O(2) on glycerol/ethanol-containing media, but we could not
      associate any transcription factor with this phenomenon. Finally, mTPx I also
      induced by t-butyl hydroperoxide in a Hap1p-independent manner. In conclusion,
      mTPx I expression is under a complex regulatory network, which involves, at
      least, two signaling pathways: one sensing the carbon source (which is signalized
      by cAMP) and the other sensing the intracellular redox state (which is signalized
      by heme).

PMID- 11827754
TI  - Post-ischemic transcriptional and translational responses of EC-SOD in mouse
      brain and serum.
AB  - Extracellular superoxide dismutase (EC-SOD) is neuroprotective, but its role in
      cerebral ischemia remains to be determined. We herein describe the topographical
      localization and quantitative changes in EC-SOD and its mRNA expression following
      cerebral ischemia in mice. Mice were subjected to transient forebrain ischemia
      and varied intervals of reperfusion. The measurements of EC-SOD using ELISA
      showed increased brain EC-SOD after 24 h of reperfusion and an increase in EC-SOD
      brain/serum ratio after 3 h. The immunohistochemical examination in normal mice
      showed strong EC-SOD immunoreactivity in the choroid plexus, pia mater, and
      ventral tuberal area of the hypothalamus. EC-SOD immunoreactivity in cortical and
      striatal capillary wall was conspicuous after 3 h. EC-SOD immunoreactivity was
      also noted in cortical neurons after 24 h. Northern blot analysis showed an
      increased EC-SOD mRNA expression in the brain after 24 h. An in situ
      hybridization study in normal mice demonstrated the mRNA expression of EC-SOD in
      choroid plexus and neurons through the brain especially in the cortex or ventral
      tuberal area of the hypothalamus, but demonstrated no mRNA expression of EC-SOD
      in the capillary wall. These findings suggest that EC-SOD accumulates on
      endothelial cells in response to this injury by an unknown mechanism, while
      cortical neurons produce EC-SOD themselves after cerebral ischemia with
      reperfusion.

PMID- 11827756
TI  - Abstracts of the 4th Oxford Glutamine Workshop.

PMID- 11827757
TI  - Independence of heritable influences on the food intake of free-living humans.
AB  - OBJECTIVE: The time of day of meal ingestion, the number of people present at the
      meal, the subjective state of hunger, and the estimated before-meal contents in
      the stomach have been established as influences on the amount eaten in a meal and
      these influences have been shown to be heritable. Because these factors
      intercorrelate, the calculated heritabilities for some of these variables might
      result indirectly from their covariation with one of the other heritable
      variables. The independence of the heritability of the influence of these four
      factors was investigated with 110 identical and 102 fraternal same-sex and 53
      fraternal mixed-sex adult twin pairs who were paid to maintain 7-d food-intake
      diaries. METHODS: From the diary reports, the meal sizes were calculated and
      subjected to multiple regression analysis using the estimated before-meal stomach
      contents, the reported number of other people present, the subjective hunger
      ratings, and the time of day of the meal as predictors. Linear structural
      modeling was applied to the beta-coefficients from the multiple regression to
      investigate whether the heritability of the influences of these four variables
      was independent. RESULTS: Significant genetic effects were found for the beta
      coefficients for all four variables, indicating that the heritability of their
      relationship with intake is to some extent independent and heritable.
      CONCLUSIONS: This suggests that influences of multiple factors on intake are
      influenced by the genes and become part of the total package of genetically
      determined physiologic, sociocultural, and psychological processes that regulate
      energy balance.

PMID- 11827758
TI  - Leptin levels and IgF-binding proteins in malnourished children: effect of weight
      gain.
AB  - OBJECTIVES: Although it is well known that leptin reflects body fat content in
      adults, the regulation of leptin levels during childhood malnutrition is poorly
      understood. Insulin-like growth factor I (IGF-I) and the IGF-binding proteins
      (IGFBPs) may play important roles in the regulation of body composition. We
      investigated the relation between leptin, IGF-I, and IGFBPs in children with
      protein-energy malnutrition (PEM; before and after recovering 10% of their
      initial body weights) in comparison with well-nourished children. METHODS:
      Fifteen PEM and 16 healthy children were studied on admission and after 10%
      weight gains in the malnourished group. Leptin was measured with
      radioimmunoassay, IGF-I and IGFBPs were measured with immunoradiometric assay.
      RESULTS: Patients with PEM had a significantly lower body mass index and
      percentage of body fat than did the control children. Before weight gain, leptin,
      IGF-I, and IGFBP-3 were significantly lower and IGFBP-1 was elevated in the
      malnourished group compared with the control group. Among PEM patients, after 10%
      weight gains, the levels of leptin, IGF-I, and IGFBP-3 were significantly higher
      and IGFBP-1 significantly lower compared with the control group. Leptin
      correlated significantly with IGF-I in the normal children (r(s) = 0.86, P <
      0.005). On admission, no correlation was observed between leptin and IGF-I (r(s)
      = 0.08, P < 0.16) and between leptin and IGFBP-3 (r(s) = 0.02, P < 0.27) in the
      malnourished group, but those levels improved after 10% recovery of their body
      weights (r(s) = 0.47, P < 0.002 and r(s) = 0.42, P < 0.005, respectively). In the
      PEM group, IGF-I correlated significantly with IGFBP-3 when the children gained
      weight (before: r(s) = 0.006, P < 0.31; after: r(s) = 0.32, P < 0.01). Our study
      showed results similar to those of anorexia nervosa studies, but the
      normalization of study variables was obtained in considerable less time for the
      same weight gain. CONCLUSIONS: The main finding of this study was that, after
      refeeding with only a 10% weight gain, the PEM children normalized their leptin,
      IGF-I, and IGFBP-3 levels. These results provide evidence that leptin can
      function as link between this hormonal response and improved nutrition status.

PMID- 11827759
TI  - Effect of age on substrate oxidation during total parenteral nutrition.
AB  - OBJECTIVE: Parenteral nutrition is increasingly used in the elderly. Aging is
      accompanied by metabolic changes that can modify substrate use. We compared
      substrate oxidation during cyclic total parenteral nutrition (TPN) in elderly and
      middle-aged patients. METHODS: Twelve elderly patients (eight women, four men; 72
      +/- 5 y) and 12 middle-aged patients (nine women, three men; 39 +/- 13 y) who
      were on cyclic TPN for intestinal failure were investigated while in stable
      condition after at least 15 d of TPN. No patient was diabetic. Indirect
      calorimetry was performed during fasting and every 30 min during the 3 h of TPN
      infusion and 3 h after infusion, allowing the measurement of nutrient oxidation.
      Blood samples were obtained every hour for the measurement of glucose, insulin,
      triacylglycerols, and free fatty acids. RESULTS: In the fasting state, resting
      energy expenditure was significantly higher in the elderly patients than in the
      middle-aged patients (39.3 +/- 8.1 versus 31.9 +/- 4.3 kcal/kg of fat-free mass
      per day, P = 0.008). During TPN, lipid oxidation was significantly higher in the
      elderly patients than in the middle-aged patients (1.09 +/- 0.17 versus 0.84 +/-
      0.27 mg x kg(-1) x min(-1), P = 0.011); glucose oxidation was significantly lower
      in the elderly patients than in the middle-aged patients (2.19 +/- 0.93 versus
      3.22 +/- 1.54 mg x kg(-1) x min(-1), P = 0.038). Areas under the curves of
      glycemia and free fatty acids were significantly higher in the elderly patients.
      CONCLUSION: In the elderly, TPN was associated with significantly higher lipid
      oxidation and lower glucose oxidation than in younger patients. TPN formulas and
      flow rates should therefore be adapted in the elderly.

PMID- 11827760
TI  - Plasma status of retinol, alpha- and gamma-tocopherols, and main carotenoids to
      first myocardial infarction: case control and follow-up study.
AB  - OBJECTIVE: Epidemiologic studies have suggested that dietary intake and plasma
      concentrations of antioxidants have an inverse relation with coronary heart
      disease. To test whether fat-soluble antioxidants can play a role against the
      occurrence of myocardial infarction (MI), we measured plasma levels of retinol,
      tocopherols, and individual carotenoids in MI patients. METHODS: A case-control
      and follow-up study of patients in the Mostoles area (Madrid, Spain). One hundred
      six patients (62 after 1 y) and 104 control subjects participated in the study.
      Blood samples were collected after overnight fast or during the first 24 h of MI
      onset for biochemical profiles of retinol, alpha- and gamma-tocopherols, and
      carotenoid by means of a quality-controlled high-performance liquid
      chromatography. RESULTS: During the acute phase after MI onset, plasma levels of
      retinol, gamma-tocopherol, and xanthophylls (lutein/zeaxanthin and beta
      cryptoxanthin) decreased, whereas alpha-tocopherol, alpha-carotene, beta
      carotene, and lycopene showed levels similar to those of control subjects.
      Logistic regression analysis showed low concentrations of gamma-tocopherol (and
      retinol) in plasma as the only statistically significant factor associated with
      MI, after adjusting for traditional risk factors. However, 1 y later, the MI
      patients showed a general improvement in plasma lipids and fat-soluble
      antioxidant status, and none of the analytes was associated with MI. CONCLUSIONS:
      The decreased plasma status of retinol, gamma-tocopherol, and xanthophylls during
      the acute phase of MI normalized the year after the MI event, suggesting that
      most subjects had followed an overall healthier lifestyle and dietary pattern.
      The results also raise concerns on the usefulness of these plasma compounds as
      specific, relevant, and predictive markers in relation to coronary heart disease.

PMID- 11827761
TI  - Determination of trace elements (Cu, Zn, Mn, Pb) and magnesium by atomical
      absorption in patients receiving total parenteral nutrition.
AB  - OBJECTIVE: We measured the serum levels of four trace elements (Cu, Zn, Mn, Pb)
      and Mg in surgical patients receiving total parenteral nutrition (TPN). The
      clinical implications and the results are discussed. METHODS: Two groups of
      patients were studied: the first group (n = 40) was our study group and the
      second (n = 40) was the control group. Four measurements of each trace element
      (TE) in blood serum were carried out: one before initiating TPN, one 24 h after,
      one 3 d later, and the last one immediately after discontinuing TPN. Each
      measurement was repeated twice. The Perkin-Elmer atomic absorption
      spectrophotometer (model 2380) with furnace graphite HGA-300 was used to measure
      the TE levels and an acetylene flame was used to measure the Mg levels. RESULTS:
      Levels of all the TEs, except Pb, were lower before the administration of TPN
      compared with the control group (P < 0.05). The levels of TEs during and
      immediately after TPN were generally lower in comparison with the initial
      measurement before the administration of TPN. CONCLUSION: The results of this
      study suggest that it may be necessary to 1) add Cu, Zn, Mn, and Mg to the
      parenteral nutritional solution and 2) follow the fluctuations in serum levels
      during the administration of TPN.

PMID- 11827762
TI  - Usefulness of soluble dietary fiber for the treatment of diarrhea during enteral
      nutrition in elderly patients.
AB  - OBJECTIVES: We investigated the clinical usefulness of soluble dietary fiber
      (SDF) for the treatment of diarrhea during enteral nutrition in elderly patients.
      METHODS: This study included 10 men and 10 women (mean age +/- standard
      deviation: 79.3 +/- 5.1 y) who had diarrhea during long-term nutrition
      management. When administering SDF, the initial dose was 7 g and thereafter
      gradually increased at 1-wk intervals. After 4 wk, the administration was
      discontinued for 2 wk to confirm the effects of SDF. RESULTS: After the
      administration of SDF, serum diamine oxidase activity significantly increased (P
      < 0.001): The water content of the feces decreased significantly after the
      administration of fiber (P < 0.01). The frequency of daily bowel movements also
      decreased significantly (P < 0.05). Simultaneously, the fecal features improved.
      Concerning intestinal flora, there were no significant changes in the total
      number of bacteria or the number of anaerobic bacteria. The fecal pH decreased
      significantly 4 wk after the administration of fiber (P < 0.05). The total level
      of short-chain fatty acids increased significantly 4 wk after the administration
      of fiber (P < 0.05). There were no significant changes in the various nutritional
      indices. CONCLUSIONS: The administration of SDF is useful for controlling
      spontaneous, favorable bowel movement by improving symptoms of small intestinal
      mucosal atrophy and normalizing the intestinal flora.

PMID- 11827763
TI  - Subclinical protein malnutrition is a determinant of hyperhomocysteinemia.
AB  - OBJECTIVES: Hyperhomocysteinemia is regarded as a public health problem of
      increasing importance likely to contribute to vascular disorders and premature
      mortality. Folate, cobalamin, pyridoxine, and riboflavin dietary deficiencies are
      currently regarded as causative factors. However, several investigations have
      indicated that the theory of vitamin B deprivation provides only a partial
      explanation for the observed abnormalities of sulfur-containing amino acids. We
      investigated the potential contributory role played by protein malnutrition.
      METHODS: For that purpose, three cohorts of 20 adult patients presenting stage I,
      II, and III goiter underwent careful medical history, dietary inquiry, and
      clinical examination. Their overall health and nutrition states were assessed
      with classic anthropometry, measurement of vitamin B blood parameters, visceral
      protein markers, essential amino acids, total homocysteine, and cystathionine.
      RESULTS: The concentrations of transthyretin, seven essential amino acids, and
      cystathionine progressively decreased as the thyroid gland increased. Methionine
      was the sole essential amino acid whose values did not change; total homocysteine
      was unique in that increased levels correlated negatively with transthyretin
      values. Taken together, the data point to a progressive deterioration of protein
      nutrition status impairing the transsulfuration pathway and is best explained by
      an acquired defect of cystathionine-beta-synthase activity. CONCLUSIONS:
      Hyperhomocysteinemia may arise from the shrinking of endogenous nitrogen pools as
      a result of decreased protein intake or stress-induced increased losses. Raised
      total homocysteine may result from the attempt of the malnourished and/or
      stressed body to preserve methionine homeostasis.

PMID- 11827764
TI  - Risk factors for vitamin D deficiency in breast-fed newborns and their mothers.
AB  - OBJECTIVES: Vitamin D plays a critically important role in the development,
      growth, and mineralization of the skeleton during its formative years, and
      performs an equally essential role in maintaining a healthy mineralized skeleton
      for adults of all ages. We evaluated the vitamin D status and risk factors for
      vitamin D deficiency in healthy breast-fed newborns and their nursing mothers.
      METHODS: Serum 25-hydroxyvitamin D (25OHD), calcium, phosphorus, and alkaline
      phosphatase levels were measured in 54 newborns and their nursing mothers whose
      ages ranged from 18 to 38 y. The relation between serum 25OHD level and
      demographic factors was analyzed. Bone mineral density was measured in the
      mothers with a serum 25OHD level below 25 nmol/L to determine the extent of bone
      mineralization. RESULTS: The mean serum 25OHD level in the 54 mothers was 29.11
      +/- 10.47 nmol/L. Forty-six percent of the mothers had serum 25OHD levels below
      25 nmol/L. The risk factors for low maternal serum 25OHD level were found in
      decreasing order of importance as follows: low socioeconomic class (odds ratio
      [OR] = 8.1, P = 0.000), being covered (OR = 4.3, P = 0.023), and low educational
      level (OR = 3.5, P = 0.033). The mean serum 25OHD level in the newborns was 18.62
      +/- 8.00 nmol/L. Eighty percent of the newborns had serum 25OHD levels below 25
      nmol/L. There was a significant correlation between the serum 25OHD levels of the
      newborns and their mothers (r = 0.63, P = 0.01). The most important risk factor
      for low serum 25OHD level in the newborn was a maternal 25OHD level below 25
      nmol/L (OR = 15.2, P = 0.002), followed a covered mother (OR = 6.8, P = 0.011).
      Bone mineral densitometry showed osteopenia in 40% of the women with serum 25OHD
      levels below 25 nmol/L. All women were from a lower socioeconomic class and 80%
      were covered. CONCLUSIONS: Vitamin D deficiency is still a common and serious
      health problem of women of reproductive age and their babies in developing
      countries at the outset of a new millennium.

PMID- 11827765
TI  - Influence of high cholesterol diet and pravastatin sodium on the initiation of
      liver regeneration in rats after partial hepatectomy.
AB  - OBJECTIVES: Liver regeneration is influenced by cholesterol and 3-hydroxy-3
      methylglutaryl coenzyme A reductase (HMG-CoA-reductase). HMG-CoA-reductase is a
      key enzyme for cholesterol synthesis. Recent studies have shown that inhibitors
      of HMG-CoA-reductase improve liver functions after 67% partial hepatectomy (PH).
      METHODS: Male Wistar rats (W) and Prague hereditary hypercholesterolemic rats
      (PHHC) were used. Aqua pro injectione (AI) or pravastatin (prava; 1 mg/kg) was
      administered orally once daily. Group 1: W, standard diet (SD) + AI; group 2: W,
      SD + prava; group 3: W, cholesterol-enriched diet (chol) + AI; group 4: PHHC,
      chol + AI; group 5: PHHC, chol + prava. After 27 d, PH was performed in all
      groups. RESULTS: Groups fed chol before PH had significantly higher liver
      triacylglycerol content (group 3: 25.8 +/- 2.6 mg/g of liver weight; group 4:
      16.0 +/- 1.0 of liver weight; group 5: 22.0 +/- 1.0 of liver weight) than did the
      groups fed SD (group 1: 6.1 +/- 0.5; group 2: 5.9 +/- 0.7). Liver DNA synthesis
      after PH was significantly lower in chol-fed groups (group 3: 561 +/- 78; group
      4: 472 +/- 92) than in SD-fed groups (group 1: 1645 +/- 574; group 2: 2935 +/-
      1298), except the chol-fed PHHC given prava (group 5: 3230 +/- 527). CONCLUSIONS:
      In prava-treated rats, the induction of HMG-CoA activity overcame the inhibitory
      capability of pravastatin. The induction of HMG-CoA-reductase activity had a
      stimulatory effect on the initiation of liver regeneration.

PMID- 11827766
TI  - Antioxidant enzyme level in the testes of cirrhotic rats.
AB  - OBJECTIVES: An understanding of the tissue and organ level of antioxidant enzymes
      that scavenge reactive oxygen species may provide an indication of their
      susceptibility to free radical-related cytotoxic damage. A direct association
      between testicular production of excessive reactive oxygen species and male
      infertility has been noted. We measured the activities of superoxide dismutase
      and glutathione peroxidase in the testes of thioacetamide-induced cirrhotic rats.
      METHODS: Antioxidant enzyme activities and trace element levels (copper, zinc,
      manganese, and selenium) in the testes of thioacetamide-induced cirrhotic and
      control rats were measured. The statistical difference between the experimental
      and control groups with regard to the activities of superoxide dismutase and
      glutathione peroxidase and levels of trace elements was analyzed with Student's t
      test. RESULTS: Our results showed a significant decrease in the activity of these
      enzymes in the testes of cirrhotic rats. The testicular levels of copper, zinc,
      and manganese, which are associated with these antioxidant enzymes, increased,
      whereas selenium decreased slightly in cirrhotic rats; that decrease was not
      statistically significant. CONCLUSIONS: Our studies showed a drastic decrease in
      the level of antioxidant enzymes in the testes of cirrhotic rats that could have
      deleterious effects on sperm function in these animals. Further studies are
      necessary to understand the exact pathways of trace element metabolism in the
      testes of cirrhotic rats.

PMID- 11827768
TI  - Dual-energy X-ray absorptiometry and body composition: differences between
      devices and comparison with reference methods.

PMID- 11827767
TI  - Dietary oils high in oleic acid but with different unsaponifiable fraction
      contents have different effects in fatty acid composition and peroxidation in
      rabbit LDL.
AB  - OBJECTIVE: We investigated the influence of different edible oils high in oleic
      acid but with different unsaponifiable fractions on the fatty acid composition
      and lipid peroxidation in plasma and low-density lipoprotein (LDL) in rabbits.
      METHODS: Thirty-two rabbits were randomly assigned to four groups of eight
      animals. For 8 wk each group was fed a semisynthetic isoenergetic diet that
      differed by lipid source (Picual virgin olive oil, Picual virgin olive oil that
      had been subjected to an exhaustive process of washing, Arbequina virgin olive
      oil, and sunflower oil high in oleic acid). We analyzed the fatty acid profile,
      thiobarbituric acid reactive substances, alpha-tocopherol, coenzyme Q, and
      retinol in plasma and the fatty acid profile, hydroperoxides, alpha-tocopherol,
      and coenzyme Q in LDL. RESULTS: The two varieties of virgin olive oil behaved
      differently from the high-oleic sunflower oil, and the effect of the different
      ratios of oleic acid to linoleic acid in the lipid sources on fatty acid
      composition in plasma and LDL was significant. With regard to oxidative stress,
      LDL in the group that ingested the lipid sources with the greatest amount of
      phenolic compounds showed the highest level of antioxidants (alpha-tocopherol and
      coenzyme Q; P < 0.05) and the lowest susceptibility to lipid peroxidation (P <
      0.05). CONCLUSION: This study provides evidence in vivo of the considerable
      antioxidant capacity of the phenolic fraction of virgin olive oil in rabbit LDL
      and the important role that this unsaponifiable fraction can play in the overall
      antioxidant benefit attributed to these oils. However, these effects depend on
      the phenolic content of the oil.

PMID- 11827769
TI  - Variations in occurrences of nutrition-related diseases in Sub-Saharan Africans
      in stages of transition: what of the future?
AB  - In many Sub-Saharan African populations, in particular urban dwellers, there have
      been marked rises in the prevalences of obesity in women, hypertension, diabetes,
      and cerebral vascular disease. Yet there have been only slight rises in coronary
      heart disease. To learn more of the roles of the various influencing factors in
      the puzzling situations described, some aspects of the past and present
      occurrences of these diseases are described and discussed, with comparisons being
      made with corresponding situations in African Americans, as well as in certain
      white populations. Despite increases in the knowledge of influencing factors,
      such fail to explain fully the epidemiologic situations described. As to the
      future, judging from the experiences of other populations, despite continuing
      indigence, within the next generation significant rises in coronary heart disease
      in certain African populations seem to be inevitable. However, in many of those
      populations, in particular those in the South, the extent of changes, apart from
      those linked with level of socioeconomic state, will be strongly affected by the
      rising epidemic of human immunodeficiency virus and acquired immunodeficiency
      syndrome.

PMID- 11827770
TI  - Dietary flavonols: chemistry, food content, and metabolism.
AB  - The flavonols belong to a large group of compounds called flavonoids, which are
      diverse in their chemical structure and characteristics. Fruits, vegetables, and
      beverages such as tea and red wine are major sources of flavonols in the human
      diet. The daily consumption of flavonols is difficult to estimate because values
      depend on accurate assessment of feeding habits and flavonol content in foods.
      Food sources, dietary intakes, and bioavailability of flavonols are strongly
      influenced by variations in plant type and growth, season, light, degree of
      ripeness, food preparation, and processing, all of which are discussed. In the
      past few years, a number of studies on the absorption and metabolism of flavonols
      in humans have been published and the findings from these studies are reviewed.
      We do not discuss the health effects of flavonols.

PMID- 11827771
TI  - Does leptin really influence cancer anorexia?

PMID- 11827772
TI  - Usefulness of lumbar AP spine DXA for measuring the percentage of perilumbar
      regional fat and predicting visceral fat in obese postmenopausal women.
AB  - We investigated whether measurement of the perilumbar regional fat amount by
      lumbar spine DXA is as good a predictor of visceral fat in obese postmenopausal
      women. Twenty-two obese (BMI 30-383 kg/m(2)) and 18 nonobese (BMI 20.1-24.7
      kg/m(2)) postmenopausal women with similar age were recruited. Lumbar AP spine
      DXA for measuring the percentage of perilumbar regional fat and CT scanning for
      estimation of the abdominal visceral fat areas were performed. In obese subjects,
      visceral fat areas as measured by CT were significantly correlated with BMI,
      waist circumference, WHR, and DXA-measured perilumbar regional fat percentage. In
      nonobese subjects, visceral fat areas measured with CT were correlated with BMI,
      waist circumference, WHR, and DXA-measured perilumbar regional fat percentage.
      The results of multiple regression analysis were that the perilumbar regional fat
      percent by DXA was the best predictor of visceral fat amount in obese
      postmenopausal women (R(2) = 0.750) and BMI predicted visceral fat amount in
      nonobese postmenopausal women (R(2) = 0.343). This study suggests that lumbar
      regional fat percentage, as measured by DXA, is a better predictor of abdominal
      visceral fat amount than waist circumference, WHR, or BMI in obese postmenopausal
      women.

PMID- 11827773
TI  - Nutritional status, iron-deficiency-related indices, and immunity of female
      athletes.
AB  - Nutritional status, iron-deficiency-related biochemical indices, and immunologic
      patterns of female Judo athletes and control subjects were evaluated. The
      subjects' 3-d food records showed that 41.0 kcal/kg of energy was consumed daily
      and the contributions of protein, fat, and carbohydrate to total energy intake
      were 12.5%, 29.2%, and 58.3%, respectively. The reported vitamin intakes of
      athletic subjects were above those of the recommended daily allowance, however,
      calcium and iron intakes were less than 100% of the recommended daily allowance.
      Intakes of energy, protein, phosphate, vitamin B1, and vitamin B2 were higher in
      the athletes than in the control subjects. Analysis using the Nutrient Adequacy
      Ratio and the Index of Nutritional Quality showed that athletic subjects had more
      desirable patterns than the control subjects. There was no any indication of
      anemia, which often occurs as a result of hemodilution in strenuously trained
      athletes. The subjects' immunologic patterns showed a slight immunosuppression.
      Iron, vitamin B1, niacin intakes were positively correlated with immunoglobulin
      (Ig) G levels in the athletes. The relation between nutrient intakes and the
      immune systems of endurance-trained athletes needs further investigation.

PMID- 11827775
TI  - Nutrition and development in Africa: risk factors on either side of the economic
      fulcrum.

PMID- 11827776
TI  - Determination of trace elements and magnesium by atomical absorption in patients
      receiving total parenteral nutrition.

PMID- 11827777
TI  - Lagging behind.

PMID- 11827778
TI  - Physiologic mechanisms to maintain methionine status during protein malnutrition.

PMID- 11827779
TI  - Rickets in the sunshine?

PMID- 11827781
TI  - The assessment and remedying of inadequate diets in India, as appreciated by Sir
      Robert McCarrison.

PMID- 11827780
TI  - Neurochemical mechanisms for cancer anorexia.
AB  - Under normal conditions, the homeostasis of energy intake is maintained in the
      hypothalamus by 1) transducing metabolic and sensorial inputs arising from the
      periphery into neuronal response, 2) integrating the information originating from
      different tissues, and 3) triggering the appropriate feeding responses. If cancer
      anorexia is considered a disruption of the physiologic mechanisms controlling
      energy intake, it is conceivable that its pathogenesis may lie in an abnormal
      input of information to the hypothalamus, its defective transduction and
      integration, or the induction of exaggerated and inappropriate feeding responses.
      Currently available data suggest that the pathogenesis of cancer anorexia is
      multifactorial and involves most of the neuronal signaling pathways modulating
      energy intake. Thus, a number of factors has been proposed as putative mediators
      of cancer anorexia, including hormones (e.g., leptin), neuropeptides (e.g.,
      neuropeptide Y), cytokines (e.g., interleukin-1, interleukin-6, tumor necrosis
      factor), and neurotransmitters (e.g., serotonin and dopamine). However, it is
      unlikely that they represent separate and distinct pathogenic mechanisms; rather,
      it appears that close interrelationships may exist among them. In line with this
      reasoning, consistent experimental and human data suggest that hypothalamic
      monoaminergic neurotransmission and serotonergic activity in particular may
      represent a major target on which different anorexia-related factors converge.
      Thus, interfering pharmacologically with hypothalamic serotonin synthesis and
      activity has been tested as a therapeutic strategy in anorectic cancer patients
      with encouraging results. However, more clinical options will be available by
      revealing the complex interactions between the many factors participating in
      controlling energy intake under normal and pathologic conditions. Further,
      modulation of hypothalamic activity also might result in reduced catabolic
      signals to skeletal muscles, thus improving the cachexia associated with cancer.

PMID- 11827782
TI  - Do you suffer from "FTI" syndrome?

PMID- 11827783
TI  - Measurement error and reliability.

PMID- 11827784
TI  - Forum on Therapeutic Nutrition: 2000 Clinical Practice Update. September 9, 2000,
      Palisades, New York, USA.

PMID- 11827785
TI  - Severe metabolic acidosis and heart failure due to thiamine deficiency.

PMID- 11827786
TI  - A portable system for pharyngeal administration of fluids.

PMID- 11827787
TI  - A report on the 3rd Workshop on Heritable Disorders of Connective Tissue.
AB  - The 3rd Workshop on Heritable Disorders of Connective Tissue was held at the
      National Institutes of Health from 16th to 18th November, 2000. The Workshop was
      sponsored by the National Institute of Arthritis and Musculoskeletal and Skin
      Diseases, NIH Office of Rare Diseases, March of Dimes, Coalition for Heritable
      Disorders of Connective Tissue, and the Foundation for Basic Cutaneous Research.
      It was supported by specific grants R13 AR46912 (US Public Health Service) and 4
      FY00-4511 (March of Dimes Birth Defects Foundation). The Workshop was divided
      into six sessions, featuring 29 invited presentations. In addition to the invited
      participants, more than eighty guests (scientists, NIH staff, and members of the
      Coalition for Heritable Disorders of Connective Tissue) attended.

PMID- 11827788
TI  - CD44-mediated uptake and degradation of hyaluronan.
AB  - Hyaluronan turnover occurs systemically from the lymph and serum as well as
      locally by the same cells responsible for its synthesis. Local turnover involves
      receptor-mediated uptake and delivery to lysosomes. Of the many hyaluronan
      binding proteins/receptors known, the participation of CD44 in the
      internalization of hyaluronan has been best characterized. Some fraction of the
      hyaluronan bound to CD44 becomes internalized and delivered to lysosomes by a
      mechanism that is not dependent on clatherin, caveolae or pinocytosis. In cells
      such as chondrocytes, anabolic and catabolic cytokines can alter the activity of
      CD44 toward hyaluronan internalization. However, the mechanism of cellular
      regulation remains unclear. Regulation may involve the participation of
      alternatively spliced isoforms of CD44, changes in CD44 phosphorylation, changes
      in cytoskeletal binding proteins or, the activity or extracellular proteolytic
      activity.

PMID- 11827789
TI  - Hyaluronan and its catabolic products in tissue injury and repair.
AB  - Hyaluronan is an unbiquitous glycosaminoglycan present in most tissues. Under
      homeostatic conditions hyaluronan exists as a high molecular mass polymer that
      has important roles in tissue structural integrity. Under conditions of stress
      such as following tissue injury, hyaluronan becomes depolymerized and lower
      molecular mass polymers are generated. The biological properties of these
      hyaluronan fragments appear to be distinct from the larger precursor molecules.
      This review examines the biological role of hyaluronan fragments in tissue injury
      and repair.

PMID- 11827790
TI  - Inhibitors of the hyaluronidases.
AB  - The inhibitors of hyaluronidase present in mammalian sera, first described half a
      century ago, have remained uncharacterized. Because of increased interest in
      hyaluronidases and their hyaluronan substrate, a study of these inhibitors was
      undertaken recently. The predominant serum inhibitor is magnesium-dependent and
      is eliminated by protease or chondroitinase digestion, and by heat. Kinetics of
      inhibition are similar against hyaluronidases from testis, snake and bee venom.
      The inhibitor has no effect on Streptomyces hyaluronidase; indicating inhibition
      is not through protection of the hyaluronan substrate. Circulating inhibition
      levels are increased in mice following carbon tetrachloride or interleukin-1
      injection, inducers of the acute-phase response. Reverse hyaluronan gel
      zymography reveals a predominant band of 120 kDa relative molecular size.
      Additional studies indicate that the inhibitor resembles a member of the Kunitz
      type inter-alpha-inhibitor family. Inhibition of hyaluronidase activity is
      observed using purified inter-alpha-inhibitor and is reversed by antibodies
      specific for inter-alpha-inhibitor. This molecule, found in the hyaluronan-rich
      cumulus mass surrounding mammalian ova and the pericellular coat of fibroblasts
      and mesothelial cells, may function to stabilize such matrices by protecting
      against hyaluronidase degradation. Turnover of circulating hyaluronan is
      extraordinarily rapid, with a half-life of two to five min. Prompt increases in
      levels of serum hyaluronan occur in patients with shock, septicemia or massive
      burns, increases that may be partly attributed to suppression by these acute
      phase reactants of the constant and rapid rates of hyaluronan degradation by
      hyaluronidase. A literature survey of other hyaluronidase inhibitors is also
      presented.

PMID- 11827791
TI  - Non-enzymatic covalent modifications of proteins: mechanisms, physiological
      consequences and clinical applications.
AB  - Given the complexity of the biosynthetic machinery and the delicate chemical
      composition of proteins, it is remarkable that cells manage to produce and
      maintain normally functioning proteins under most conditions. However, it is now
      well known that proteins are susceptible to various non-enzymatic covalent
      modifications (NECM) under physiological conditions. Such modifications can be of
      no or little importance to the protein or they can be absolutely detrimental.
      Often NECM are difficult to study due to the complex and technically demanding
      methods required to identify many of these modifications. Thus, the role of NECM
      has not yet been adequately resolved but recent research has allowed a better
      understanding of such modifications. The present review outlines the various
      forms of NECM that involve covalent modifications of proteins, and discusses
      their relevance, biological impact and potential applications in the study of
      protein turnover and diagnosis of disease.

PMID- 11827793
TI  - Identification and analysis of collagen alpha 1(XXI), a novel member of the FACIT
      collagen family.
AB  - The FACIT collagens bind to the surface of collagen fibrils linking them with
      other matrix molecules. Bioinformatics analysis of cDNA clone DKFZp564B052 showed
      that it resembled the FACIT collagens and was therefore designated collagen alpha
      1(XXI). Phylogenetic analyses of the N-terminal NC3 domains of alpha 1(XXI) and
      other FACIT collagens showed that (i) alpha 1(XXI) clustered with the FACIT
      collagens; (ii) collagen alpha 1(XXI) arose before the divergence of alpha
      1(XII), alpha 1(XIV) and alpha 1(XX); (iii) collagen alpha 1(XIV) derived from
      the C-terminal region of the NC3 domain of a collagen alpha 1(XII)-like molecule;
      and (iv) collagen alpha 1(XX) derived from a collagen alpha 1(XIV)-like molecule.
      This study provides a framework for the evolution of the FACIT collagens which
      will be of value in linking NC3 domains with their functions.

PMID- 11827792
TI  - Temporal expression of CD44 during embryonic chick limb development and
      modulation of its expression with retinoic acid.
AB  - Hyaluronan-cell interactions are initiated co-ordinately with mesenchymal
      condensation during chondrogenic differentiation in the limb bud. Hyaluronan is
      responsible for the retention and organization of proteoglycan within the
      cartilage matrix. Hyaluronan-CD44 binding also retains proteoglycan aggregates to
      the chondrocyte plasma membrane. A sequence for CD44 protein in chick has
      recently been reported, but never evaluated in chick chondrocytes. Total RNA was
      isolated from embryonic chick limb buds, stages 18, 19, 24, 25 and 30. Using semi
      quantitative RT-PCR, expression of aggrecan, this chick CD44 orthologue and GAPDH
      mRNA was analyzed. Aggrecan expression was detected at all stages, but was
      increased at stage 30. CD44 mRNA was detected at extremely low levels at stage 18
      to higher levels in the latter stages. Thus, the temporal expression of CD44 mRNA
      correlated with the onset of pre-cartilage condensation. The full-length chick
      chondrocyte CD44 cDNA was obtained following RT-PCR using RNA derived from tibial
      chondrocytes from stage 37 chick embryos. The nucleotide sequence was used to
      generate an amino acid sequence and analyses revealed homologies of 44.4% with
      mouse, 47.8% with bovine and 46.3% with human CD44. Tibial chondrocytes were
      cultured in the presence or absence of retinoic acid for 36 or 72 h. By RT-PCR,
      expression of aggrecan and the CD44 mRNA by chick chondrocytes was decreased
      after retinoic acid treatment, while GAPDH expression showed no change. As
      expected, control chondrocytes exhibited a round morphology while retinoic acid
      treated chondrocytes were elongated. The retinoic acid-treated chondrocytes also
      exhibited reduced hyaluronan binding. This functional assay indicates a role for
      a CD44 receptor in matrix retention by chick chondrocytes.

PMID- 11827794
TI  - Actin stress fibres and cell-cell adhesion molecules in tendons: organisation in
      vivo and response to mechanical loading of tendon cells in vitro.
AB  - Tendons consist of parallel longitudinal rows of cells separated by collagen
      fibres. The cells are in intimate contact longitudinally within rows, and
      laterally via sheet-like lateral cell processes between rows. At points of
      contact, they are linked by gap junctions. Since tendons stretch under load, such
      cell contacts require protection. Here we describe the organisation of the actin
      cytoskeleton and actin-based cell-cell interactions in vivo and examine the
      effect of cyclic tensile loading on tendon cells in vitro. Cells within
      longitudinal rows contained short longitudinally running actin stress fibres.
      Each fibre was aligned with similar fibres in the cells longitudinally on either
      side, and fibres appeared to be linked via adherens junctions. Overall, these
      formed long oriented rows of stress fibres running along the rows of tendon
      cells. In culture, junctional components n-cadherin and vinculin and the stress
      fibre component tropomyosin increased in strained cultures, whereas actin levels
      remained constant. These results suggest that: (1) cells are linked via actin
      associated adherens junctions along the line of principal strain; and (2) under
      load, cells appear to attach themselves more strongly together, and assemble more
      of their cytoplasmic actin into stress fibres with tropomyosin. Taken together,
      this suggests that cell-cell contacts are protected during stretch, and also that
      the stress fibres, which are contractile, may provide an active mechanism for
      recovery from stretch. In addition, stress fibres are ideally oriented to monitor
      tensile load and thus may be important in mechanotransduction and the generation
      of signals passed via the gap junction network.

PMID- 11827795
TI  - Sorsby's fundus dystrophy tissue inhibitor of metalloproteinases-3 (TIMP-3)
      mutants have unimpaired matrix metalloproteinase inhibitory activities, but
      affect cell adhesion to the extracellular matrix.
AB  - The TIMP family of matrix metalloproteinase inhibitors consists of four members,
      of which TIMP-1, -2 and -4 are secreted, freely diffusible proteins, whereas TIMP
      3 is ECM-associated. Mutations in the TIMP3 gene have been linked to Sorsby's
      fundus dystrophy (SFD), an autosomal dominant inherited retinal degenerative
      disease that leads to blindness. The SFD mutations characterized result in
      introduction of an unpaired cysteine residue in the C-terminal domain of TIMP-3.
      We have expressed four SFD mutant TIMP-3 proteins in baby hamster kidney (BHK)
      cells and evaluated their characteristics alongside wild-type TIMP-3. Analysis of
      the mutant proteins (Ser156Cys, Gly167Cys, Tyr168Cys and Ser181Cys) by SDS-PAGE
      and reverse zymography revealed that each of the mutants retained gelatinase A
      and gelatinase B inhibitory activity, and were localized to the ECM. Association
      rate constants for Ser156Cys TIMP-3 with gelatinase-A, gelatinase-B, stromelysin
      1 and collagenase-3 were only moderately reduced compared to wild-type TIMP-3.
      However, all of the mutants displayed aberrant protein-protein interactions,
      resulting in the presence of additional proteins or complexes in ECM
      preparations. Two of the mutants (Ser156Cys and Ser181Cys) showed a marked
      propensity to form multiple higher molecular-weight complexes that retained TIMP
      activity on reverse zymography. Expression of the SFD mutant TIMP-3 (and to a
      lesser extent, wild-type TIMP-3) proteins in BHK cells conferred increased cell
      adhesiveness to the ECM. Our findings indicate that the pathogenesis of Sorsby's
      fundus dystrophy cannot be attributed to a failure to localize SFD TIMP-3
      proteins to the ECM or defects in MMP inhibition, but may involve the formation
      of aberrant TIMP-3-containing protein complexes and altered cell adhesion.

PMID- 11827796
TI  - Developmentally regulated expression of type XV collagen correlates with
      abnormalities in Col15a1(-/-) mice.
AB  - Lack of type XV collagen in mice results in mild skeletal myopathy and increases
      vulnerability to exercise-induced skeletal muscle and cardiac injury [Proc. Natl.
      Acad. Sci. USA 98 (2001), 1194]. The expression of type XV collagen was studied
      during murine fetal development from 10.5 to 18.5 dpc using immunofluorescence.
      The first sign of type expression was seen in the capillaries of many tissues at
      10.5 dpc, some of them showing developmental transitions in the expression.
      Interestingly, capillaries forming the blood-brain barrier and those of the
      sinusoidal type were essentially lacking in this collagen. Early expression was
      also detected in the skeletal muscle and peripheral nerves, while expression in
      the heart, kidney and lung appeared to be developmentally regulated. In addition,
      distinct staining was found in the perichondrium of the cartilage. Collectively,
      the dynamics of its expression during development, its localization in the
      basement membrane--fibrillar matrix interface and the consequences of its absence
      in mice suggest a structural role in providing stability at least in skeletal
      muscle and capillaries. The early prominent expression of type XV collagen in
      newly forming blood vessels could also indicate a possible role in angiogenic
      processes.

PMID- 11827798
TI  - The role of antibodies to Plasmodium falciparum-infected-erythrocyte surface
      antigens in naturally acquired immunity to malaria.
AB  - Plasmodium falciparum, the most virulent species of human malaria parasite,
      causes 1-3 million deaths per year. Because this parasite is susceptible to
      naturally acquired host immunity the main burden of diseases falls on young
      children. The mechanism of this immunity is still unclear. However, the parasite
      makes a considerable investment in the insertion of highly polymorphic antigens
      (parasite-infected-erythrocyte surface antigens, PIESA) on the infected
      erythrocyte surface, and these antigens are potentially important immune targets.

PMID- 11827797
TI  - Differential regulation of MMP-1/9 and TIMP-1 secretion in human monocytic cells
      in response to Mycobacterium tuberculosis.
AB  - In tuberculosis, matrix metalloproteinase (MMP) secretion is involved in
      leukocyte migration to sites of infection but in excess may contribute to tissue
      destruction. We demonstrate that human monocytic THP-1 cells and primary
      monocytes secrete MMP-1 (52 kD collagenase) when phagocytosing live, virulent M.
      tuberculosis but not inert latex. The magnitude of MMP-1 secretion was
      approximately 10-fold less when compared to MMP-9 (92 kD gelatinase) secretion.
      MMP-1 secretion was also relatively delayed (detected at 24 h vs. 4 h). M.
      tuberculosis, zymosan or latex stimulate similar TIMP-1 secretion within 8 h and
      increasing over 24 h. MMP-1/9 secretion was decreased by inhibitors of protein
      kinase (PK) C, PKA or tyrosine kinases (PTK) in a concentration-dependent manner.
      In contrast, TIMP-1 secretion was not affected by PKC or PTK blockade and only
      somewhat reduced by high level PKA inhibition. In summary, M. tuberculosis
      infected monocytes secrete MMP-1 at lower concentrations than MMP-9 and such MMP
      secretion is regulated by multiple upstream signalling pathways which do not
      control TIMP-1 secretion. Divergent effects of i on MMP and TIMP secretion from
      monocytes may be important in influencing matrix degradation in vivo.

PMID- 11827799
TI  - Quickening the pace of anthrax research: three advances point towards possible
      therapies.
AB  - Anthrax toxin is the dominant virulence factor of Bacillus anthracis and drugs
      blocking its action could therefore have therapeutic benefit. Three recent papers
      suggest new ways to inhibit the toxin. Identification of the cell surface toxin
      receptor could lead to the design of binding competitors and receptor decoys.
      Determination of the crystal structure of the lethal factor protease will
      facilitate ongoing efforts to develop protease inhibitors as therapies. Finally,
      the susceptibility of certain inbred mice to anthrax lethal toxin was associated
      with mutations in the kinesin-like protein Kif1C, a discovery that could help to
      explain how anthrax toxin kills animals.

PMID- 11827800
TI  - Animal usage in vaccine development and production: maximising results while
      minimizing use.
AB  - The Third International Symposium on Advancing Science and Elimination of the Use
      of Laboratory Animals for Development and Control of Vaccines and Hormones,
      organized by the National Institute of Public Health and the Environment (RIVM,
      The Netherlands) under the auspices of the International Association for
      Biologicals (IABS), was held in Utrecht, The Netherlands, 12-14 November 2001.

PMID- 11827801
TI  - Poking holes in pneumococci.

PMID- 11827803
TI  - Mopping up transcription factors.

PMID- 11827806
TI  - Mycobacterium smegmatis and tuberculosis.

PMID- 11827807
TI  - Acid survival of Helicobacter pylori: how does urease activity trigger
      cytoplasmic pH homeostasis?
AB  - Helicobacter pylori can survive for several hours at pH 1 in the presence of
      urea. Under these conditions, the organism maintains its cytoplasmic pH at a
      value close to neutral. The role of the cytoplasmically located urease enzyme in
      this process is a matter of debate. We propose that cytoplasmic ammonia generated
      by the action of urease is protonated by H(+) ions leaking in from the acidic
      medium and that the NH(4)(+) formed is extruded from the cytoplasm via an as-yet
      unidentified transport system. This mechanism is compared with the general
      mechanism of cytoplasmic pH homeostasis in microorganisms.

PMID- 11827808
TI  - Host association of Borrelia burgdorferi sensu lato--the key role of host
      complement.
AB  - Borrelia burgdorferi sensu lato (s.l.), the tick-borne agent of Lyme borreliosis,
      is a bacterial species complex comprising 11 genospecies. Here, we discuss
      whether the delineation of genospecies is ecologically relevant. We provide
      evidence that B. burgdorferi s.l. is structured ecologically into distinct
      clusters that are host specific. An immunological model for niche adaptation is
      proposed that suggests the operation of complement-mediated selection in the
      midgut of the feeding tick. We conclude that vertebrate hosts rather than tick
      species are the key to Lyme borreliosis spirochaete diversity.

PMID- 11827809
TI  - The pathobiology of Paracoccidioides brasiliensis.
AB  - Paracoccidioides brasiliensis causes one of the most prevalent systemic mycoses
      in Latin America--paracoccidioidomycosis. It is a dimorphic fungus that undergoes
      a complex transformation in vivo, with mycelia in the environment producing
      conidia, which probably act as infectious propagules upon inhalation into the
      lungs, where they transform to the pathogenic yeast form. This transition is
      readily induced in vitro by temperature changes, resulting in modulation of the
      composition of the cell wall. Notably, the polymer linkages change from beta
      glucan to alpha-glucan, possibly to avoid beta-glucan triggering the inflammatory
      response. Mammalian oestrogens inhibit this transition, giving rise to a higher
      incidence of disease in males. Furthermore, the susceptibility of individuals to
      paracoccidioidomycosis has a genetic basis, which results in a depressed cellular
      immune response in susceptible patients; resistance is conferred by cytokine
      stimulated granuloma formation and nitric oxide production. The latency period
      and persistence of the disease and the apparent lack of efficacy of humoral
      immunity are consistent with P. brasiliensis existing as a facultative
      intracellular pathogen.

PMID- 11827810
TI  - The functions of Ca(2+) in bacteria: a role for EF-hand proteins?
AB  - In bacteria, Ca(2+) is implicated in a wide variety of cellular processes,
      including the cell cycle and cell division. Dedicated influx and efflux systems
      tightly control the low cytoplasmic Ca(2+) levels in prokaryotes. Additionally,
      the growing number of proteins containing various Ca(2+)-binding motifs supports
      the importance of Ca(2+), which controls various protein functions by affecting
      protein stability, enzymatic activity or signal transduction. The existence of
      calmodulin-like proteins (containing EF-hand motifs) in bacteria is a long
      standing hypothesis. Analysis of the prokaryotic protein sequences available in
      the databases has revealed the presence of several calmodulin-like proteins
      containing two or more authentic EF-hand motifs, suggesting that calmodulin-like
      proteins could be involved in Ca(2+) regulation in bacteria.

PMID- 11827811
TI  - Comparative genomics of closely related salmonellae.
AB  - As the number of completed genome sequences increases, there is increasing
      emphasis on comparative genomic analysis of closely related organisms. Comparison
      of the similarities and differences between the five publicly available
      Salmonella genome sequences reveals extensive sequence conservation among the
      Salmonella serovars. However, horizontal gene transfer has provided each genome
      with between 10% and 12% of unique DNA. Genome comparisons of the closely related
      salmonellae emphasize the insights that can be gleaned from sequencing genomes of
      a single species.

PMID- 11827812
TI  - Epidemic dengue/dengue hemorrhagic fever as a public health, social and economic
      problem in the 21st century.
AB  - Dengue fever/dengue hemorrhagic fever is now one of the most important public
      health problems in tropical developing countries and also has major economic and
      societal consequences.

PMID- 11827817
TI  - Human gene discovery through experimental definition of transcribed regions of
      the human genome.
AB  - The sequencing of the human genome has failed to realize its primary goal: the
      identification of all human genes. We have learned that genes can only be
      identified with certainty within this vast and information-sparse structure by
      comparison with transcript sequences. Significantly more sequence data of this
      kind is required before we can claim to have deciphered our genetic blueprint.

PMID- 11827818
TI  - Large-scale mutational analysis for the annotation of the mouse genome.
AB  - After sequencing the human and mouse genomes, the annotation of these sequences
      with biological functions is an important challenge in genomic research. A major
      tool to analyse gene function on the organismal level is the analysis of mutant
      phenotypes. Because of its genetic and physiological similarity to man, the mouse
      has become the model organism of choice for the study of genetic diseases. In
      addition, there is at the moment no other vertebrate for which versatile
      techniques to manipulate the genome are as well developed. Several mouse
      mutagenesis projects have provided the proof-of-principle that a systematic and
      comprehensive mutagenesis of every gene in the mammalian genome will be feasible.
      An exhaustive functional annotation of the mammalian genome can only be achieved
      in a combination of phenotype- and gene-driven approaches in large- and small
      scale academic and private projects. Major challenges will be to develop
      standardised phenotyping protocols for the clinical and pathological
      characterisation of mouse mutants, the improvement of mutation detection methods
      and the dissemination of resources and data. Beyond gene annotation, it will be
      necessary to understand how gene functions are integrated into the complex
      network of regulatory interactions in the cell.

PMID- 11827819
TI  - High-density genotyping and linkage disequilibrium in the human genome using
      chromosome 22 as a model.
AB  - Technology and genetics have advanced to the point where genotyping thousands of
      individuals at thousands of marker locations around the whole human genome is
      possible. The whole-genome scan for detection of complex disease genes is a
      widely discussed topic. We review some of the recent high-density genotyping
      experiments and discuss related details, particularly the extent and variability
      of linkage disequilibrium. We also discuss the quality of single nucleotide
      polymorphisms (SNPs) in public databases and its consequences to the number of
      SNPs required for large-scale genotyping projects.

PMID- 11827820
TI  - Large-scale genotyping by mass spectrometry: experience, advances and obstacles.
AB  - Single nucleotide polymorphism (SNP) genotyping has become a key technology for
      genetic studies. In recent years, matrix-assisted laser desorption/ionization
      (MALDI) time-of-flight mass spectrometry has emerged as a very powerful method
      for SNP genotyping. Here, we discuss our experience in implementing a high
      throughput SNP genotyping facility based on MALDI, and the issues encountered in
      adapting this to large-scale genetic studies. Most of these issues are not
      specific to using MALDI approaches, and they will also serve as valuable pointers
      for establishing high-throughput genotyping with other methods.

PMID- 11827821
TI  - Genome and protein evolution in eukaryotes.
AB  - The past year has seen the completion of the genome sequence of the flowering
      plant Arabidopsis thaliana and the initial sequence reports of the human genome.
      The availability of completely sequenced eukaryotic genomes from disparate
      phylogenetic lineages has opened the door to comparative analyses and a better
      understanding of the evolutionary processes shaping genomes. Complex many-to-many
      relationships between genes from different species appear to be the norm,
      suggesting that transfer of detailed functional annotation will not be
      straightforward. In addition to expansion and contraction of gene families, new
      genes evolve from recombination of pre-existing domains, although some domain
      families do appear to have evolved recently and to be specific to restricted
      phylogenetic lineages. The overall picture is of a huge diversity of gene content
      within eukaryotic genomes, reflecting different functional demands in different
      species.

PMID- 11827822
TI  - Two-dimensional gel electrophoresis: recent advances in sample preparation,
      detection and quantitation.
AB  - A strength of two-dimensional polyacrylamide gel electrophoresis (2D PAGE) is its
      ability to resolve and investigate the abundance of several thousand proteins in
      a single sample. This enables identification of the major proteins in a tissue or
      subcellular fraction by mass spectrometric methods. In addition, 2D PAGE can be
      used to compare quantities of proteins in related samples, such as those from
      altered environments or from mutant and wild type, thus allowing the response of
      classes of proteins to be determined. Those proteins showing a correlated
      difference in expression may participate in related processes, and this
      subsequently helps to define protein function. Although there are many
      limitations of the 2D gel technology that mean it will never be comprehensive in
      protein coverage, its use for the identification of relatively abundant proteins
      is now widespread. However, there are still surprisingly few examples of
      quantitative analysis of changes in protein abundance. In this review we
      highlight recent advances towards true quantitative analysis of 2D gels that will
      lead to better prediction of protein function. Despite the development of
      promising alternatives, 2D PAGE is likely to remain in extensive use for the
      foreseeable future, because the technology is now simple and readily available to
      many laboratories.

PMID- 11827823
TI  - Lab-on-a-chip: applications in proteomics.
AB  - Recent advances in chip-based separation of proteins provide methods that are
      faster and more convenient than conventional gel electrophoresis. Rapid and
      automated protein sizing on a chip is at the commercial stage and first attempts
      have been made to perform two-dimensional separation on a chip. Numerous designs
      have been described to interface a microfluidic chip to a mass spectrometer.
      Impressive integration efforts are demonstrated by the ability to perform on-chip
      trypsin digestion, separation and injection into a mass spectrometer with a
      single device.

PMID- 11827824
TI  - Two-hybrid arrays.
AB  - The two-hybrid system is a genetic method for detecting protein-protein
      interactions. The assay can be applied to random libraries or arrays of colonies
      that express defined pairs of proteins. Arrays enable the testing of all possible
      protein pairs for interactions in a systematic fashion. The array format makes a
      large number of individual assays comparable and thus greatly simplifies the
      identification of false positives. Two-hybrid arrays have been used to study
      interactions among the proteins of yeast, hepatitis C virus, vaccinia virus,
      Drosophila, Caenorhabditis elegans, mouse and other species, and have already
      identified thousands of interactions.

PMID- 11827825
TI  - Rainbow's end: the quest for multiplexed fluorescence quantitative analysis in
      proteomics.
AB  - During the past two years, the performance of fluorescence-based protein
      detection methods has demonstrably eclipsed conventional technologies such as
      colloidal Coomassie Blue and silver staining with respect to detection
      sensitivity, quantitative accuracy and compatibility with modern protein
      identification and characterization procedures. At this point, fluorescence-based
      methods are poised to offer unprecedented new capabilities in proteomics
      investigations through the performance of multi-parameter quantitative
      measurements. The feasibility of such measurements has already been demonstrated
      through the specific detection of antibiotic-binding proteins, drug-metabolizing
      enzymes or post-translationally glycosylated proteins, along with the total
      protein expression profile from electrophoretically separated, complex biological
      specimens.

PMID- 11827826
TI  - Emerging array-based technologies in proteomics.
AB  - Microarray format is the method of choice for high-throughput hybridization of
      nucleic acids. Lately, microarray strategy has been applied to broad studies of
      interactions of proteins with other molecules. The diversity of these
      interactions and variations of the properties of proteins present new challenges
      to microchip technology. Significant achievements have been reported. In
      particular, three-dimensional (gel-based) chips can be manufactured with limited
      resources and offer flexibility, capacity, homogeneous solvent environment and
      the ability to record processes in real time and in variable conditions.

PMID- 11827827
TI  - Miniaturised multiplexed immunoassays.
AB  - Miniaturised immunoassays are of general interest for applications that require
      the simultaneous determination of different parameters from a minute sample of
      material. Apart from planar microarray-based systems, bead-based flow cytometric
      approaches are well suited for the multiplexed detection of target molecules,
      especially when the number of parameters that have to be determined in parallel
      is limited.

PMID- 11827828
TI  - Functional protein microarrays.
AB  - Microarrays of immobilized functional proteins have the potential to increase
      dramatically the throughput of proteomic analysis. Micro-immunoassays, in which
      biological samples are exposed to arrays of immobilized antibodies, can be used
      for protein expression profiling. In addition, protein function can be elucidated
      by performing binding and enzymatic assays on arrays of biologically active
      proteins.

PMID- 11827829
TI  - Current achievements using ProteinChip Array technology.
AB  - Because of its inherent flexibility, the ProteinChip Array platform has
      demonstrated utility into basic research as well as clinical research. In the
      domain of basic research, it has been used to examine protein modifications,
      characterize protein-protein interactions and study signal transduction and
      enzymatic pathways. In clinical research, it has been used to elucidate and
      identify biomarkers of disease, and as a platform for predictive medicine.

PMID- 11827830
TI  - One from column A and two from column B: the benefits of phage display in
      molecular-recognition studies.
AB  - Recent uses of phage-displayed combinatorial peptide and cDNA libraries have
      proven invaluable in mapping protein-protein interactions, protein-drug
      interactions, and the generation of 'molecular therapeutics'. This article
      reviews some of the findings of the past year and points out some of the pros and
      cons of phage display as compared with those of yeast two-hybrid screening.

PMID- 11827831
TI  - Clinical and functional target validation using tissue and cell microarrays.
AB  - Expression levels of thousands of genes or proteins can be readily determined
      using microarray techniques. However, this represents only the first step in
      understanding the biological and medical significance of these molecules. New
      high-throughput techniques, such as tissue and cell microarrays, will facilitate
      clinical and functional analysis of molecular targets.

PMID- 11827832
TI  - Accelerating code to function: sizing up the protein production line.
AB  - High-throughput biology has been pioneered by genomics through the application of
      robotics to expedite DNA-sequencing projects. Advances in high-throughput protein
      methods are needed to drive the protein production line for high-throughput
      structural and functional analysis of newly discovered genes. This will require
      the development and application of a variety of recombinant-protein expression
      systems to produce the diversity of proteins from both humans and model
      organisms.

PMID- 11827833
TI  - Yeast mitochondrial biogenesis: a model system for humans?
AB  - Recently, our knowledge of yeast mitochondrial biogenesis has considerably
      progressed. This concerns the import machinery that guides preproteins
      synthesized on the cytoplasmic ribosomes through the mitochondrial outer and
      inner membranes, as well as the inner membrane insertion machinery of
      mitochondrially encoded polypeptides, or the proteins participating in the
      assembly and quality control of the respiratory complexes and ATP synthase. More
      recently, two new fields have emerged, biosynthesis of the iron-sulfur clusters
      and dynamics of the mitochondrion. Many of the newly discovered yeast proteins
      have homologues in human mitochondria. Thus, Saccharomyces cerevisiae has proven
      a particularly suitable simple organism for approaching the molecular bases of a
      growing number of human mitochondrial diseases caused by mutations in nuclear
      genes identified by positional cloning.

PMID- 11827834
TI  - Initial treatment of symptomatic mild to moderate bronchial asthma with the
      salmeterol/fluticasone propionate (50/250 microg) combination product (SAS
      40023).
AB  - BACKGROUND: Chronic controller therapy, particularly with inhaled
      corticosteroids, is required in patients with persistent bronchial asthma. Long
      acting beta agonists provide prolonged bronchodilatation, improve symptoms and
      reduce exacerbations. A powder inhaler containing both fluticasone propionate and
      salmeterol xinafoate combines anti-inflammatory treatment and bronchodilatation
      in a single user-friendly device (Diskus). OBJECTIVE: The goal of the present
      study was to evaluate the efficacy and safety of salmeterol/ fluticasone (50/250
      microg twice daily) as initial treatment for symptomatic patients with mild to
      moderate bronchial asthma who had not previously received appropriate anti-asthma
      medication. METHODS: This prospective study was conducted in 17 study centres
      located predominantly in private practices. 127 patients with mild to moderate
      asthma (FEV(1) >60% of predicted) aged 12 years and older were recruited into a
      one-week screening phase. If they used rescue medication on > or =3 of 7 days or
      had a total asthma symptom score of > or =5 points, they were admitted to the
      treatment phase and received salmeterol xinafoate (50 microg) and fluticasone
      propionate (250 microg) in a single dry powder inhaler (Diskus) for four weeks.
      RESULTS: Combined salmeterol/fluticasone therapy improved morning and evening
      peak expiratory flow rates (PEFR) as measured by patients and reported in asthma
      diaries within the first week of treatment (by 35 and 28 L/min, respectively). At
      week 4, morning PEFR had increased by 57 L/min or 13.0 % predicted compared to
      baseline, and forced expiratory volume in one second (FEV1) had improved by 12.5%
      of predicted (p<0.001). Use of rescue medication declined by 1.9 puffs per day.
      Both patients and physicians regarded treatment as a major benefit: two thirds
      assessed treatment as "excellent". The combination was well tolerated.
      CONCLUSIONS: The combined inhalation of salmeterol and fluticasone from a single
      dry powder inhaler (DiskuS) was an effective initial treatment for patients with
      mild to moderate asthma. Improvements of symptoms and lung function were
      documented by the first week of treatment. This combination provides rapid and
      effective asthma control that is highly acceptable to both the patient and
      physician.

PMID- 11827836
TI  - Monitoring of endogenous interferon-alpha and human herpesvirus 8 in HIV-infected
      patients with Kaposi's sarcoma.
AB  - The incidence of AIDS-associated Kaposi's sarcoma has declined since the mid
      nineties due to the availability of potent antiretroviral therapy including
      protease inhibitors. However, Kaposi's sarcoma is still the most common neoplasia
      in HIV-infected patients. In the pathogenesis of the HIV-associated as well as
      other forms of this disease an infectious agent seems to play a role, namely the
      human herpesvirus 8. Even before the discovery of the HIV virus, high levels of
      an unusual acid-labile form of endogenous interferon alpha were found in patients
      with AIDS-associated KS. The administration of recombinant interferon alpha
      evolved as standard therapy for Kaposi's sarcoma in HIV-infected patients with a
      moderate immunodeficiency in addition to antiretroviral therapy. This
      investigation monitored the levels of HHV 8 and endogenous interferon in 4
      patients with and without Kaposi's sarcoma during the course of HIV-disease. The
      results of our experiments lead us to two hypotheses: First of all, the pre
      therapeutic level of endogenous interferon may be a predictor of the response to
      an interferon-alpha therapy for HIV-associated Kaposi's sarcoma. Secondly, the
      determination of HHV 8 DNA in blood of HIV-positive patients may allow
      conclusions about the risk for the development of Kaposi's sarcoma. However these
      hypotheses should be tested by monitoring the levels of endogenous interferon and
      HHV 8 DNA in clinical studies of a greater number of HIV-infected patients.

PMID- 11827835
TI  - How do adolescents with juvenile chronic arthritis consider their disease related
      knowledge, their unmet service needs, and the attractiveness of various services?
AB  - AIMS: To explore the information needs of adolescents with juvenile chronic
      arthritis (JCA) with respect to patient education and other measures to promote
      self-management. METHODS: Standardized cross-sectional inquiry concerning disease
      related knowledge, perceived importance of information giving, unmet needs as
      well as perceived attractiveness of a range of services (lecture, structured
      patient education, support group, self-help group) to promote self-management.
      SAMPLE: N = 48 adolescents (68% of all adolescents with JCA of our outpatient
      clinic); mean age x = 14.9 (+/- 2.1) years; 56% female; 17% had the
      oligoarthritis form of JCA, 40% juvenile spondylarthritis, 25% polyarthritis and
      systemic form, 19% other rheumatic diseases. RESULTS: The majority of adolescents
      considered themselves as sufficiently well-informed and voted in favour of
      detailed information giving. However, 30% were unsatisfied with their current
      information and knowledge. Information needs predominantly related to the
      prognosis, course, and treatment of JCA, whereas the psychosocial impact (except
      sports and job matters) were judged as less important. Adolescents with a lower
      level of education were generally more interested than those with a high level of
      education. As for the attractiveness of services nearly half of the adolescents
      judged all of them as not very attractive. CONCLUSIONS: The majority of
      adolescents is interested in detailed information giving and some of them point
      to unmet needs, but nearly half of them is hesitant towards services which are
      delivered in a group format (such as structured patient education or support
      groups).

PMID- 11827837
TI  - Amebic liver abscess--rare need for percutaneous treatment modalities.
AB  - BACKGROUND: Given the often unspecific symptoms of amebic liver abscess, an
      analysis was done to recognize the most common patterns of presentation. Since
      treatment recommendations are still inconsistent comparing conservative and
      interventional treatment modalities, we evaluated treatment modalities in our
      patients. METHODS: A retrospective case series of all patients with confirmed
      amebic liver abscess was conducted. Age, sex, country of origin or travel,
      symptoms, and physical and laboratory findings were recorded. Particular
      attention was given to the need for interventional measures. RESULTS: 62 patients
      were reviewed, and nearly all of them (95%) had a travel history. The most common
      findings were fever (97%), abdominal pain (95%), and hepatomegaly (79%). 11%
      still had no amebic antibodies on presentation but an increase in the follow-up
      examinations. In 5% needle aspiration was performed to allow differentiation
      between amebic and pyogenic etiology. Metronidazole alone quickly cleared
      symptoms in 92% of the patients. In 8% only, there was a therapeutic need for
      interventional procedures (3% already ruptured, 5% large abscess formation with
      the danger of rupture). CONCLUSIONS: In travelers with fever, abdominal pain, and
      hepatomegaly amebic liver abscess must be considered. Medical treatment with
      metronidazole is effective in more than 90%. Only in very few cases there is a
      need for invasive therapeutic modalities.

PMID- 11827839
TI  - Validity of patient-supplied medical history data comparing two medical
      questionnaires.
AB  - In many European countries there has been a significant shift in the age
      structure of the population, resulting in a marked rise in the number of elderly,
      medically compromised patients. Early identification of possible medical risk
      factors is therefore increasingly gaining in importance in the treatment of
      dental patients. It was the aim of the present study to evaluate two different
      patient-administered questionnaires with a view to both the validity of medical
      history data supplied by the patients and the identification of a possible risk
      potential. A comprehensive form (A, specially designed for treatment under
      general anaesthesia, 50 questions) and a shorter form (B, for routine use in
      general dental practices, 37 questions) were randomly distributed to patients of
      two dental practices (n = 194). Data supplied by the patients were checked
      against those provided by the general practitioners and risk assessment was
      performed based on the American Society of Anaesthesiologists (ASA) physical
      status classification system. A total of 161 medical history forms were evaluated
      (A: 81 test persons, B: 80 test persons). A close relationship was observed
      between increased age and higher ASA classification. The evaluation of the two
      history forms yielded an overall sensitivity of 80% for form A and of 61% for
      form B (specificity 96% and 98%, respectively). With both forms, agreement
      between the data supplied by the patients and by the dental practitioner was
      highest for ASA Grade I patients (A: 88%, B:02%). However, agreement between
      patient and general practitioner-supplied data was lower for ASA Grade III
      patients with both forms (A: 92%, B: 72%). Risk overestimation with form A
      occurred in 6 % and with form B in 5% of cases, while the medical risk was
      underestimated with form A in 5% and with form B in 11% of cases. Although
      results of the present study emphasise the need for meticulous and thorough
      history taking, neither the more concise form B nor the more comprehensive and
      detailed form A was able to exclude the occurrence of false-positive or false
      negative answers. Particularly the lack of validity observed for patient-supplied
      data, which resulted in higher medical risk classifications despite the use of a
      comprehensive medical history questionnaire, mandates the improvement and
      possible reorientation of interdisciplinary co-operation between the dentist and
      the general practitioner.

PMID- 11827838
TI  - Effect of antiretroviral combination therapies including efavirenz in heavily
      pretreated HIV-infected children.
AB  - BACKGROUND: In this retrospective study the effect of antiretroviral combination
      regimens including the non nucleoside reverse transcriptase inhibitor (NNRTI)
      efavirenz (EFV) on viral load (VL) and CD4-cell count in heavily pretreated HIV
      infected children was investigated. DESIGN: The data of 15 children (< 16 years)
      were evaluated during a treatment period of at least 52 weeks. Patients received
      a median of 4 prior antiretroviral regimens and were changed to combinations with
      EFV because of renewed increasing VL. METHODS: Viral load (Amplicor, detection
      limit 50 copies/ml) and CD4-cells were measured every 4-8 weeks. RESULTS: The
      median reduction of the viral load for the total study population was 1.9 log10
      (0.8 - 4.7), 2.3 log(10) (0.5 - 4.7) and 2.6 log(10) (0-4.7) after 12, 24 and 52
      weeks, respectively. After 24 weeks 7/15 children and after 52 weeks 9/15
      patients had reductions of the VL below the detection limit. The median increase
      of CD4-cells in the study population during the treatment period were 104
      cells/microl (189-969), 220 cells/microl (170-831) and 321 cells/ml (162-574)
      after 12, 24 and 52 weeks, respectively. CONCLUSIONS: In children with intensive
      prior antiretroviral therapy and multiple therapeutic failures with PI-containing
      regimens, combination therapy including EFV resulted in an excellent
      antiretroviral efficacy. After 52 weeks 9/15 patients had persistent reductions
      of the VL below 50 copies/ml, although none of these children reached this level
      of viral suppression during their multiple prior protease inhibitor-containing
      regimens.

PMID- 11827841
TI  - [How to evaluate a child following a first seizure?].
AB  - Following a first epileptic phenomenon in a child, detailed history-taking, age
      at onset and complete clinical examination are essential. Previously experienced
      paroxysmal episodes may correspond to undiagnosed seizures. It is important to
      inquire about the existence of subjective sensations preceding or initiating
      attacks, about postictal phenomena such as confusion or drowsiness and about the
      circumstances of occurrence of the seizures. Clinical examination should look for
      any neurological signs, cutaneous stigmata or dysmorphic features. Parents should
      be asked about any recent changes in behaviour or school performances.
      Interictal, and eventually ictal, EEG data must be interpreted within the general
      neurological context. In the majority of cases, careful analysis of all the above
      mentioned data leads to a diagnostic hypothesis on the type(s) of seizures and,
      sometimes, on the epilepsy syndrome. Indications for further investigations,
      including MRI, will be discussed on the basis of a precise hypothesis. Treatment
      with antiepileptic drugs should not usually be started at the first seizure, with
      the exception of some epilepsy syndromes characterized by regular seizure
      relapse.

PMID- 11827842
TI  - [From historical EEG to signal treatment: applications in childhood epilepsy].
AB  - Electroencephalography is a fundamental investigation for the characterization of
      an epilepsy. It remains a unique way for the evaluation of a cortical activity in
      real time. The classification of epileptic syndromes is based on electroclinical
      correlations. The characterization of EEG abnormalities is essential for
      establishing a specific syndromic diagnosis. Discussing the historical evolution
      of EEG techniques we show how the recent development of numerized EEG provided
      the medical community with very useful and simple tools for the treatment of EEG
      signals. These tools are now integrated in everyday clinical practice. Several
      methods are presented, illustrating potential applications in childhood
      epilepsies.

PMID- 11827840
TI  - Interferon-alpha in treatment of chronic hepatitis C in co-infected HIV-patients
      in combination with ribavirin and as a pre-load therapy in treatment-naive HIV
      positive patients. 8th European Conference on Clinical Aspects and Treatment of
      HIV Infection (8th ECCATH), 29-31 October, Athens Greece.
AB  - Though AIDS-related morbidity and mortality are generally decreasing as a result
      of highly active antiretroviral therapy (HAART) and prevention of opportunistic
      infections, dual infection with HCV and HIV leads to an acceleration in the
      natural course of chronic hepatitis C (cHC) and worsening of associated liver
      disease and complications. Mortality from co-morbid HCV infection within this
      population is increasing and has become a major challenge in the management of
      HIV-related complications. As treatment strategies to fight cHC have been
      essentially ameliorated within the recent two years in using pegylated interferon
      alfa2b (Peg-IFN-alfa2b) combined with ribavirin, t here is hope that the
      successful therapeutic outcomes in HCV-mono-infected individuals may be partly
      translated into benefits for the difficult-to-treat patients with HCV-HIV co
      infection. A number of issues arise when beginning HCV treatment during HAART, as
      for instance possible interactions with antiretroviral therapies, increased risk
      of special side effects, and a compromise in adherence due to the addition of new
      medication in patients already taking several drugs. On the other hand there is
      also the chance that Peg-IFN-alfa2b fights HIV as well as HCV. First data of pre
      load therapy with Peg-IFN-alfa2b in treatment-na ve HIV-positive individuals
      before the initiation of HAART have also been presented during the 8th European
      Conference on Clinical Aspects and Treatment of HIV Infection (8th ECCATH),
      October 2001 in Athens.

PMID- 11827843
TI  - [Video-EEG monitoring in neonates: indications].
AB  - In neonates with paroxysmal events, video-EEG monitoring proves to be a powerful
      tool for diagnosis. It allows differentiation of epileptic seizures from other
      paroxysmal phenomena; a more precise analysis of clinical semiology of seizures;
      it may help in the localization of a seizure focus; it provides more
      comprehensive data for the evaluation of the interictal state.

PMID- 11827844
TI  - [Cerebral imaging in childhood epilepsy: what's new?].
AB  - The important development of non invasive techniques of cerebral imaging
      dramatically improved the presurgical work-up and the study of mental sequelae in
      childhood epilepsy. MRI's spatial resolution improved, so it is possible to
      detect subtle epileptogenic lesions, even in very young patients. By visualizing
      more and more accurately the sulcogyral macroanatomy, MRI permits a genetic and
      syndromic approach of cerebral lesions associated with epilepsy. Ictal SPECT
      helps localizing the epileptogenic zone and placing intracranial EEG electrodes,
      using strict methodology with simultaneous video-EEG and multidisciplinary
      interpretation of the images. Functional MRI can localize motor cortex and
      language networks, as well as it can lateralize language with a good correlation
      with WADA test, using selected activation tasks in cooperative children.
      Interictal SPECT and PET show the dysfunctioning areas involved in the
      neuropsychological and behavioural disorders associated with epilepsy. Finally,
      fMRI may study post-lesional and post-surgical plasticity by comparing
      longitudinal studies in a given patient.

PMID- 11827845
TI  - [New antiepileptic drugs in childhood epilepsies: indications and limits].
AB  - Regarding the antiepileptic drugs (AEDs) in children, it was recently shown that
      they have a specific profile of efficacy and also of worsening according to the
      different epilepsy syndromes. However, the therapeutic profile of the most recent
      compounds is still not completely established in children because of the high
      number of syndromes and the difficulty to perform controlled studies in this age
      range. Controlled studies are most often first performed in adults and they begin
      in children whereas the new drug is already approved. However, some new AEDs
      dramatically improved seizure control, particularly in some severe epilepsy
      syndromes such as West syndrome and Lennox-Gastaut syndrome. Vigabatrin
      demonstrated a remarkable efficiency in infantile spasms whereas it tends to
      worsen myoclonic epilepsies, absence epilepsy and idiopathic partial epilepsy.
      Lamotrigine is efficient in absence epilepsy and symptomatic or cryptogenic
      generalized epilepsies such as Lennox-Gastaut syndrome and myoclonic astatic
      epilepsy. By contrast, lamotrigine increases the frequency of seizures in severe
      myoclonic epilepsy in infancy (Dravet syndrome) as well as in some cases of
      idiopathic partial epilepsy. Felbamate remains indicated as third line drug in
      refractory Lennox-Gastaut syndrome provided blood parameters are controlled. The
      therapeutic profile of oxcarbazepine is closed to that of carbamazepine. The
      efficacy of topiramate was demonstrated in partial epilepsy, but the other
      indications remain to be precised. Pediatric studies using gabapentin and
      tiagabine disclosed encouraging results in partial epilepsy. Clinical trials with
      stiripentol represent an example of strategy for developing a new AED in
      children; it recently demonstrated, in association with clobazaru, efficacy in a
      severe myoclonique epilepsy in infancy.

PMID- 11827846
TI  - [Epilepsy and childhood learning disabilities].
AB  - Epilepsy is very frequent in childhood. Learning disabilities in epilepsy are not
      very well known. Even if mental retardation has been studied, very few teams have
      focused on the different cognitive functions in children with epilepsy. Several
      neuropsychological studies have been carried out but only on epileptic syndromes
      as West syndrome and Lennox-Gastaut syndrome. It looks very important to study
      the neuropsychological profiles in the different types of epilepsy in childhood
      (generalized and partial epilepsy, idiopathic and non idiopathic). Different
      tools are now available for detection of cognitive deficits.

PMID- 11827847
TI  - [Neuropsychology and academic achievement of epileptic children: executive
      functions tests].
AB  - Children with epilepsy are exposed to learning disabilities. In young children,
      still not taught reading, spelling or mathematics, the standardized psychometric
      evaluation provides a usefull assessment tool enabling identification of the
      structural disturbances that will affect the learning process. For school-age
      children, assessment can be made in regard to the DSM IV criteria of specific
      learning disabilities, and within a neuropsychological framework that pays a
      particular attention to the executive functions.

PMID- 11827848
TI  - [Cognitive consequences of Rolandic Epilepsy].
AB  - Idiopathic focal epilepsies and particularly rolandic epilepsy are considered to
      have an excellent outcome with spontaneous recovery during adolescence. The
      characterization of this syndrome in 1959 by Beaussart and Nayrac was a great
      progress for childhood epileptology: the existence of a focal epilepsy with a
      good prognosis and no underlying brain lesion, so-called "benign" epilepsy, was
      recognized. Since the first descriptions, numerous neuropsychological studies
      were performed showing variable results. All the studies agree with the fact that
      children with rolandic epilepsy keep a normal global intellectual efficiency and
      a good long-term outcome. Nevertheless, some children may suffer transiently
      during the active phase of the epilepsy from oromotor dysfunction,
      neuropsychological deficits, or attention deficits with learning disorders. The
      analysis of cognitive and neurophysiological correlations evidenced a significant
      correlation between the epileptic focus localization and few specific
      dysfunctions. We evidenced mainly a significant effect of the persistence of a
      prolonged slow focus and a strong activation of night EEG spike and waves on
      cognitive decline and attention disorders. These abnormalities are mainly
      observed during severe or atypical evolutions of rolandic epilepsy. Preliminary
      longitudinal studies show that these cognitive deficits are transient. Thus, the
      presence of an active epileptic focus, without underlying brain lesion, could
      interfere with normal maturation of cognitive function.

PMID- 11827849
TI  - [Are idiopathic generalized epilepsies of childhood really benign?].
AB  - Most of the idiopathic generalized epilepsies are considered as benign in
      childhood. Using literature data and some personal investigations, we screened
      the cognitive impairment and school difficulties observed in children with
      idiopathic generalized epilepsies, especially absence epilepsies, myoclonic
      epilepsies considered as non-severe, and generalized epilepsies with tonico
      clonic seizures. In a controlled study concerning typical absence epilepsy, we
      have shown a lack of high or moderately elevated level of non-verbal and total IQ
      scores on Wechsler's tests (WISC III); we also observed a significant impairment
      of memory, a lengthening of school realisations, concerning motor skills and
      alertness and also hyperactivity and/or attention disorders, concerning 35 to 50%
      of cases. Most of these children present with school difficulties, of variable
      degree. These results show that the term "benign" is not appropriate in many
      cases of so-called benign idiopathic generalized epilepsies.

PMID- 11827850
TI  - [Language and learning disorders in epilepsy with continuous spike-waves during
      slow sleep].
AB  - Efficacy of antiepileptic drugs in children with epilepsy is usually evaluated on
      the basis of reduction in seizure frequency. However, in a number of cases, the
      effect of a drug in reducing EEG paroxysmal activity should be considered. This
      applies particularly to Landau-Kleffner syndrome and to the syndrome of
      continuous spike-waves during slow sleep. In developmental language disorders,
      EEG paroxysmal activity is present in almost 30% of the cases. Paroxysmal
      abnormalities are usually less frequent than what is observed in epilepsy with
      continuous spike-waves during slow sleep. Pathogenesis remains unknown and the
      relationship between EEG evolution and language improvement is not as clear as in
      Landau-Kleffner syndrome.

PMID- 11827851
TI  - [Cognitive impairment in childhood epilepsy: the role of antiepileptic drugs].
AB  - Cognitive and behavioral impairment are more frequent in epileptic children than
      in the general population. Respective role of seizures, cerebral lesion and
      antiepileptic drugs is difficult to identify, especially in severe epilepsy.
      Nevertheless, the possible negative effect of treatment on cognitive performance
      is a constant preoccupation for parents. Despite numerous clinical investigations
      this remains questionable. Methodological difficulties could in part explain
      contradictory results obtained for a given drug. The most recent data suggest
      that antiepileptic drugs used in monotherapy (with the exception of
      phenobarbital) do not have clear effect on cognitive and behavioral development
      in children. This does not exclude individual sensibility observed in clinical
      practice. Identifying clinical risk factors for significant cognitive adverse
      effects may help prescription. For the new antiepileptic drugs few additional
      studies are needed to define cognitive and behavioral profiles.

PMID- 11827852
TI  - [Psychopathology in children with epilepsy. Specific information about epilepsy].
AB  - Childhood epilepsy is frequently concomitant with emotional and
      psychopathological difficulties. A specific prevention workout of the
      psychosocial risks is always necessary and should be considered as a major task
      by the treating physician. Quality of the information provided by the physician
      and listening to the parents and the child are important factors that will
      influence the follow-up.

PMID- 11827853
TI  - Where cardiac surgery and interventional cardiology merge: the future of catheter
      based interventions for cardiovascular disease.

PMID- 11827854
TI  - Is the future of cardiac surgery in the hands of the interventional cardiologist?

PMID- 11827855
TI  - Angiogenesis: protein, gene, or cell therapy?

PMID- 11827856
TI  - Closed chest CABG on the beating heart with a computer-enhanced articulating
      system: case report.

PMID- 11827857
TI  - Pearls and pitfalls: lessons learned in endoscopic robotic surgery- the da Vinci
      experience.
AB  - The da Vinci telemanipulation system (Intuitive Surgical, Mountain View, CA) is a
      computer-enhanced instrumentation system that has helped to overcome some of the
      limitations of traditional endoscopic instruments. As of May 2001, a total of
      1,250 endoscopic cardiac procedures have been performed using the da Vinci
      system. With the use of wristed instruments and a new generation of endoscopic
      stabilizers, total endoscopic coronary artery bypass grafting on the beating
      heart has been achieved in 56 cases. Mitral valve repair and closure of atrial
      septal defects have been performed successfully through 1 cm incisions in 140
      patients. The development of adjunct technologies as well as integration of image
      based navigation systems may help to expand the use of computer-enhanced
      instrumentation systems in the near future.

PMID- 11827858
TI  - Anesthesia for robotic heart surgery: an overview.

PMID- 11827859
TI  - An alternative arterial conduit for totally endoscopic multivessel coronary
      artery bypass.
AB  - BACKGROUND: The ultimate goal of coronary artery bypass grafting (CABG) is the
      performance of a totally endoscopic procedure using multiple arterial conduits.
      At our center we have been routinely performing endoscopic robotic harvesting of
      internal thoracic arteries (ITAs) for use in minimally invasive CABG. The right
      gastroepiploic artery (RGEA) has been shown to be a reliable and versatile
      arterial conduit for bypass to coronary vessels not easily accessible by an ITA.
      The RGEA has already been harvested less invasively through a small laparotomy.
      This procedure could be made even less invasive by harvesting the RGEA
      laparoscopically, but this procedure has not yet been reported. The purpose of
      this study was to develop an endoscopic technique for harvesting the RGEA and
      demonstrate the safety and efficacy of this less invasive approach. METHODS:
      Twenty Duroc X Hampshire swine were administered general anesthesia and
      intubated. Ten mm and 5 mm trocars were then inserted. A 10 mm, 30-degree
      endoscope was adapted to a voice-activated robotic arm (AESOP), and the RGEA was
      harvested totally endoscopically using 5 mm harmonic scalpel shears.
      Intraoperative events and RGEA harvest times were recorded, and RGEA flows were
      measured after harvest. RGEA was delivered into the pericardial sac
      endoscopically. RESULTS: All RGEAs were successfully harvested without injury.
      Harvest time averaged 29.9+/- 10.9 min. The harvested conduits averaged 24.7+/-
      2.37 cm in length. Flows were excellent in all harvested conduits, averaging
      81.1+/- 31.8 cc/min. The harmonic scalpel controlled all RGEA branches with
      excellent hemostasis. CONCLUSION: The RGEA can be harvested safely through port
      access with robotic assistance. This conduit is of sufficient length to be used
      as an alternative arterial conduit for totally endoscopic multivessel coronary
      artery bypass.

PMID- 11827860
TI  - Minimally invasive approaches to coronary revascularization in high-risk
      patients.

PMID- 11827861
TI  - Stress and inflammatory response after beating heart surgery versus conventional
      bypass surgery: the role of thoracic epidural anesthesia.
AB  - Cardiac surgery elicits a cascade of stress responses mediated by the release of
      various cytokines and stress hormones [Roth-Isigkeit 1998]. Apart from the stress
      induced by the surgical process, cardiopulmonary bypass (CPB) has been documented
      to play a major role in the perioperative stress response seen following cardiac
      surgery [Butler 1993, McBride 1995, Hall 1997]. The imbalance in pro- and anti
      inflammatory responses may affect outcome in cardiac surgery patients [Casey
      1993, McBride 1995, Menasch 1995]. Contact of blood with the CPB circuit, along
      with hypoperfusion of various organs prior to and during CPB, may aggravate this
      stress response and contribute to adverse outcomes in the perioperative period
      [Casey 1993, Menasch 1995, Tonnesen 1996]. Splanchnic hypoperfusion that occurs
      in cardiac surgery patients [Landow 1991] can result in increased permeability of
      the gut mucosal barrier, resulting in endotoxemia and release of proinflammatory
      cytokines. Lungs and kidneys play a role in sequestrating the proinflammatory
      cytokines and, in the presence of hypoperfusion, may be damaged by these
      cytokines [Gilliland 1999, Liebold 1999, Gormley 2000]. Avoiding CPB may reduce
      this stress response. Anesthetic techniques such as thoracic epidural analgesia
      (TEA) that improve splanchnic perfusion [Moore 1995, Kapral 1999, Ai 2001] may
      have a role in improving patient outcome. It is further known that ischemic
      myocardium can be a major source of proinflammatory cytokines [Wan 1999a]. The
      cardiac sympathetic block resulting from TEA has been shown to reduce ischemia
      reperfusion injury [Blomberg 1989, Blomberg 1990, Liem 1992a, Liem 1992b, Liem
      1992c, Kirno 1994, Stenseth 1994]. Beating heart surgery done without the aid of
      CPB significantly attenuates cytokine and stress response [Brasil 1998, Fransen
      1998, Gu 1998, Wan 1999b, Ganapathy 1999a, Ganapathy 2000a]. There is reduced
      renal dysfunction following beating heart surgery [Ascione 1999], which may be
      related to reduced proinflammatory cytokine surge. Thoracic epidural analgesia
      inhibits intraoperative cortisol as well as catecholamine surge but does not add
      further to the reduction in cytokine response [Ganapathy 1999b].

PMID- 11827862
TI  - Hybrid strategies in minimally invasive revascularization.

PMID- 11827863
TI  - Atraumatic coronary artery bypass (ACAB): techniques and outcome.

PMID- 11827864
TI  - Hemodynamic stability and lessons learned: a four-year OPCAB experience.

PMID- 11827865
TI  - Relative recirculation: what does it mean?

PMID- 11827866
TI  - Watching the brain work: looking at the network connections.

PMID- 11827867
TI  - Transient ischemic attacks: added specificity from modern MR imaging.

PMID- 11827868
TI  - Diffusion-weighted imaging in the distinction of benign from metastatic vertebral
      compression fractures: is this a numbers game?

PMID- 11827869
TI  - Abnormalities in the recirculation phase of contrast agent bolus passage in
      cerebral gliomas: comparison with relative blood volume and tumor grade.
AB  - BACKGROUND AND PURPOSE: Abnormalities in the recirculation phase of the passage
      of a contrast agent bolus have been identified in tumors and have been suggested
      to represent vascular tortuosity and hypoperfusion in areas of angiogenic
      neovascularization. This study was performed to examine the hypothesis that these
      abnormalities provide information concerning the microcirculation related to
      tumor grade in patients with cerebral glioma. METHODS: Contrast-enhanced dynamic
      susceptibility MR imaging was performed in 27 patients with glioma. Residual
      relaxivity effects were minimized by injection of contrast agent before dynamic
      imaging. Maps of relative cerebral blood volume (rCBV) and relative recirculation
      (rR) were calculated, and values from enhancing tumor tissue were compared with
      tumor grade. RESULTS: Histologic grades were grade II, astrocytoma (n = 3); grade
      III, anaplastic astrocytoma (n = 10); and grade IV, glioblastoma multiforme (n =
      14). rCBV values varied among tumor grades, with higher mean values in higher
      grade tumors (P <.001). Mean rR values in grade II tumors were not significantly
      different from those in normal gray and white matter. Mean rR values in grades
      III and IV tumors were similar and were significantly higher than those in grade
      II tumors (P <.01). The distribution of the pixel values of rR showed significant
      differences between grades III and IV tumors (P <.001), with low values of
      skewness in keeping with a normal distribution in grade III tumors and higher
      values in grade IV tumors. CONCLUSION: Variation in the recirculation
      characteristics of a contrast agent bolus is related to tumor grade in gliomas.
      This supports the hypothesis that abnormalities in contrast agent recirculation
      provide independent information concerning the microcirculation in imaging
      studies of angiogenesis and may be of value as surrogate markers in trials of
      antiangiogenic therapy.

PMID- 11827870
TI  - Comparison of gadobenate dimeglumine and gadopentetate dimeglumine: a study of MR
      imaging and inductively coupled plasma atomic emission spectroscopy in rat brain
      tumors.
AB  - BACKGROUND AND PURPOSE: After the advent of extracellular contrast media,
      hepatobiliary-specific gadolinium chelates were developed to improve the
      diagnostic value of MR imaging of the liver. Gadobenate dimeglumine (Gd-BOPTA) is
      a new paramagnetic contrast agent with partial biliary excretion that produces
      prolonged enhancement of liver parenchyma on T1-weighted images. However, whether
      Gd-BOPTA is useful as a contrast agent in central nervous system disease,
      particularly in brain tumors, is unclear. METHODS: The behavior of Gd-BOPTA as a
      brain tumor-selective contrast agent was compared with that of gadopentetate
      dimeglumine (Gd-DTPA), an MR contrast agent used in central nervous system
      disease, in a common dose of 0.1 mmol/kg. An MR imaging study of these two
      contrast agents was performed, and tissue concentrations were measured with
      inductively coupled plasma atomic emission spectroscopy (ICP-AES). RESULTS: Gd
      BOPTA showed better MR imaging enhancement in brain tumors than did Gd-DTPA at
      every time course until 2 hours after administration and no enhancement in
      peritumoral tissue and normal brain. Corresponding results with ICP-AES showed
      significantly greater uptake of Gd-BOPTA in tumor samples than that in
      peritumoral tissue and normal brain 5 minutes after administration. Gadolinium
      was retained for a longer time in brain tumors when Gd-BOPTA rather than Gd-DTPA
      was administered. CONCLUSION: Gd-BOPTA is a useful contrast agent for MR imaging
      in brain tumors and possibly an effective absorption agent for neutron capture
      therapy.

PMID- 11827871
TI  - Change in brain size during and after pregnancy: study in healthy women and women
      with preeclampsia.
AB  - BACKGROUND AND PURPOSE: Qualitative decreases in maternal brain size have been
      observed late in pregnancy. The aim of this study was to quantitatively evaluate
      changes to the maternal brain during and after healthy pregnancy and to compare
      these changes with those observed in cases of preeclampsia. METHODS: Three
      dimensional T1-weighted MR volume images were obtained in nine healthy
      participants before and after delivery. Additional images were obtained in some
      of these participants before pregnancy, during pregnancy, and within 52 weeks
      after delivery. Five women with preeclampsia were examined before delivery and 6
      weeks after delivery. Three of these patients were examined within 52 weeks after
      delivery. Images were registered, and both brain and ventricular volumes were
      calculated by using a semiautomated computer program. RESULTS: Both the healthy
      and preeclamptic groups had a reduction in brain size during pregnancy that was
      maximal at term and that reversed by 6 months after delivery. The ventricular
      size showed a corresponding increase in size during pregnancy and a decrease in
      size after delivery. In the preeclamptic patients, brain size was significantly
      smaller (P =.05) than in healthy participants, both before and after delivery.
      CONCLUSION: The brain decreases in size during pregnancy and increases in size
      after delivery. The changes follow a consistent time course in each woman. The
      mechanism and physiologic importance of these findings are speculative at the
      present time.

PMID- 11827872
TI  - MR analysis of the substantia innominata in normal aging, Alzheimer disease, and
      other types of dementia.
AB  - BACKGROUND AND PURPOSE: The substantia innominata can be visualized on coronal
      thin-section T2-weighted MR images. The purpose of this study was to investigate
      the morphologic changes of the substantia innominata in normal aging by using MR
      imaging and to determine whether the changes in this structure on MR images were
      specific to Alzheimer disease (AD). METHODS: The thickness of the substantia
      innominata was measured on the coronal T2-weighted image obtained through the
      anterior commissure in 39 healthy control subjects (age range, 25-86 y; mean age,
      62 y); 39 patients with AD; and 36 patients with non-AD dementia, including
      vascular dementia, frontotemporal dementia, and Parkinson disease with dementia.
      RESULTS: In the control subjects, the thickness of the substantia innominata
      significantly decreased with age. Compared with age-matched control subjects,
      both patients with AD and patients with non-AD dementia had significant atrophy
      of the substantia innominata. The thickness of the substantia innominata
      significantly correlated with scores from the Mini-Mental State Examination in
      patients with AD but not in patients with non-AD dementia. CONCLUSION: MR
      analysis reveals age-related shrinkage of the substantia innominata. Atrophy of
      the substantia innominata, which reflects degeneration in the nucleus basalis of
      Meynert, is pronounced both in patients with AD and in those with non-AD
      dementia. MR imaging features in this structure may not be specific to AD.

PMID- 11827873
TI  - Past glory and future promise: maximizing and improving understanding of atrophy
      patterns in the diagnosis of degenerative dementias.

PMID- 11827874
TI  - Radial width of the temporal horn: a sensitive measure in Alzheimer disease.
AB  - BACKGROUND AND PURPOSE: Atrophy in the medial temporal lobe (MTL) structures
      depicted with brain imaging is one of the most accurate markers of Alzheimer
      disease (AD), but practical considerations have thus far limited their routine
      clinical use. The aim of this study was to explore the validity of a CT- and MR
      based measure of MTL atrophy that would be feasible for routine clinical use.
      METHODS: We acquired brain CT scans in the temporal lobe plane with thin sections
      in 42 patients with AD and in 29 control patients without dementia. We also
      acquired MR images (according to a 3D magnetization-prepared rapid gradient-echo
      protocol) in 28 patients with AD and in 28 control subjects without dementia. The
      radial width of the temporal horn (rWTH) of the lateral ventricle was measured
      with a precision caliper at the tip of the horn on CT scans or high-quality MR
      images. The validity of the rWTH variable was assessed by test-retest and
      interrater reliability, convergent and discriminant validity compared with
      progressively distant brain regions, and known-group validity (accuracy of the
      separation of patients with AD from control subjects). Convergent and
      discriminant validity compared with volumetric measures was tested in the
      patients who underwent MR imaging. RESULTS: Intraclass correlation coefficients
      for inter- and intrarater reliability were between 0.94 and 0.98. On CT scans,
      Pearson's correlation of the rWTH with the transverse width of the temporal horn
      was between 0.60 and 0.79; with Jobst's minimum thickness of the MTL, between
      0.63 and 0.78 (interuncal distance approximately 0.50); and with an index of
      frontal atrophy, between 0.35 and 0.42. On MR images, the correlation with
      volumetric MR measures was 0.80 in the temporal horn, 0.74 in the hippocampus,
      0.68 in the temporal lobe, 0.58 in the entorhinal cortex, and 0.49 in the frontal
      lobe. On CT scans (cutoff value for AD, >5.3 mm; age range of subjects, 50-90 y),
      the rWTH measure was a sensitive marker for AD in 39 of 42 patients with AD
      (sensitivity, 93%) and was a specific marker in 28 of the 29 control patients
      (specificity, 97%). On MR images (cutoff 3.6-6.7 mm; age range of subject, 50-90
      y), the rWTH was a sensitive marker for AD in 21 of 28 patients with AD
      (sensitivity, 75%) and was a specific marker in 26 of 28 control subjects
      (specificity, 93%). The accuracy of other linear CT-based measures of MTL atrophy
      and linear and volumetric MR-based measures was lower. With specificity set to
      95%, sensitivity ranged from 57% to 74% for CT-based measures and from 52% to 74%
      for MR-based measures. CONCLUSION: The rWTH is an accurate marker of AD that
      could be used in routine clinical settings.

PMID- 11827875
TI  - Comparison of independent component analysis and conventional hypothesis-driven
      analysis for clinical functional MR image processing.
AB  - BACKGROUND AND PURPOSE: With independent component analysis (ICA), regions of
      activation can be identified on functional MR (fMR) images without a priori
      knowledge of expected hemodynamic responses. The purpose of this study was to
      compare the results of fMR imaging data processed with spatial ICA with results
      obtained with conventional hypothesis-driven analysis. METHODS: Eleven patients
      with focal cerebral lesions and one with agenesis of the corpus callosum were
      enrolled. Each patient performed text-listening, finger-tapping, and word
      generation tasks. Conventional activation maps were generated by fitting time
      courses of each voxel to a boxcar reference function. Maps were created from the
      same image data with ICA techniques. To compare the maps, a concurrence ratio
      (CR) (number of voxels activated on both maps to number of voxels activated on
      either map) was calculated. RESULTS: In the ICA analysis, maps with appropriate
      spatial and temporal features for auditory, sensorimotor, or language cortices
      were identified in most patients. Images processed with ICA resembled images
      processed with conventional means. In patients who moved or performed the task
      incorrectly, ICA produced a map that resembled the expected activation pattern
      but differed from the conventional image. CRs averaged 70% for all comparisons in
      the 12 patients. CONCLUSION: fMR imaging maps for auditory, sensorimotor, and
      language tasks produced with ICA and conventional techniques were similar in most
      cases. Differences were consistent with the particular characteristics of the
      method. In data sets corrupted by motion or incorrect task performance, ICA may
      produce more accurate maps.

PMID- 11827876
TI  - Quantitative functional MR imaging of the visual cortex at 1.5 T as a function of
      luminance contrast in healthy volunteers and patients with multiple sclerosis.
AB  - BACKGROUND AND PURPOSE: In patients with multiple sclerosis (MS), a few
      preliminary functional MR (fMR) imaging studies of the visual cortex reveal
      information about magnitude differences between healthy individuals and patients
      with MS at only a single luminance level. We therefore investigated whether
      varying luminance contrast levels can help uncover subtle changes in fMR imaging
      characteristics of the visual cortex in healthy volunteers and patients with MS.
      METHODS: Blood oxygenation level-dependent fMR imaging signal changes in the
      primary visual cortex were examined as a function of luminance contrast at 1.5 T
      in 10 healthy volunteers and nine patients with MS. Ten axial sections through
      the calcarine fissure were obtained with an echo-planar T2*-weighted imaging
      sequence (4000/54/1 [TR/TE/excitation]; field of view, 220 mm; voxel size, 1.72 x
      1.72 x 5 mm). The imaging series consisted of an alternating 20-second rest epoch
      (black screen) with a 20-second activation epoch (flickering checkerboard)
      repeated six times. Each imaging series used a graded increase of eight luminance
      contrast levels. A paired t test between rest and activation images was used to
      analyze significant (P <.001) contiguous voxels in the region of interest
      (primary visual cortex). RESULTS: A progressive increase in fMR imaging
      activation across all luminance contrast levels in healthy controls and patients
      with MS was shown. The patients with MS had a significantly lower magnitude in
      the number of fMR imaging activated voxels at all luminance contrast levels (P
      <.001). A statistically significant increase in fMR imaging activation
      (activation threshold) was seen at the second luminance contrast level in
      controls and at the seventh level in patients with MS. CONCLUSION: Quantifiable
      changes in blood oxygenation level-dependent signal and a progressive increase in
      activated voxels within the primary visual cortex with increasing luminance
      contrast were demonstrated at 1.5 T in controls. The patients with MS showed a
      significant decrease in the number of activated voxels and an increase in
      activation threshold compared with healthy controls.

PMID- 11827878
TI  - Diffusion-weighted MR imaging in the acute phase of transient ischemic attacks.
AB  - BACKGROUND AND PURPOSE: Radiologic assessment of acute transient ischemic attacks
      (TIAs) has been handicapped by the low sensitivity of CT and conventional MR
      imaging for acute small-vessel infarction and the difficulty in differentiating
      between acute and chronic lesions by use of these methods. Our purpose was to
      evaluate the incidence of TIA-related infarction by using diffusion-weighted MR
      imaging to determine whether the presence of a diffusion imaging abnormality
      correlates with the duration of symptoms or cause of TIA. METHODS: We
      prospectively studied 58 consecutive patients with acute TIA by use of diffusion
      weighted imaging. All MR imaging was performed with a 1.5-T whole-body system
      with 24-mT/m gradient strength and an echo-planar-capable receiver. All patients
      were imaged within 10 days of stroke onset. RESULTS: Thirty-nine patients (67%)
      manifested a diffusion imaging abnormality consistent with acute ischemia.
      Cortical lesions were identified in 54% of these patients; most of them
      associated with other acute ischemic lesions. Subcortical lesions were identified
      in 46%; most of them were isolated from other lesions. The mean duration of
      symptoms in patients with no TIA-related diffusion imaging abnormalities was 0.96
      hours (median, 0.33 hours) compared with a mean of 6.85 hours (median, 1.53
      hours) in patients with diffusion imaging abnormalities (P =.025, Mann-Whitney U
      test). This significant correlation between the duration of TIA symptoms and the
      presence of TIA-related abnormalities was lost when we excluded from the analysis
      patients whose symptoms lasted longer than 6 hours (P =.513, Mann-Whitney U
      test). No significant correlation was observed between the size of TIA-related
      lesions and the duration of symptoms or cause of TIA. CONCLUSION: Two thirds of
      our TIA patients showed focal abnormalities indicative of acute ischemic lesions
      on diffusion-weighted images. This incidence is higher than that previously
      reported in the literature. The presence of such abnormalities increased with
      increasing total symptom duration, but this relation was not observed when only
      patients whose symptoms lasted less than 6 hours were considered. No significant
      correlation was observed between the cause and presence of TIA-related lesions on
      diffusion-weighted MR images. These TIA-related lesions are probably irreversible
      and may lead to subsequent infarct.

PMID- 11827877
TI  - High-resolution line scan diffusion tensor MR imaging of white matter fiber tract
      anatomy.
AB  - BACKGROUND AND PURPOSE: MR diffusion tensor imaging permits detailed
      visualization of white matter fiber tracts. This technique, unlike T2-weighted
      imaging, also provides information about fiber direction. We present findings of
      normal white matter fiber tract anatomy at high resolution obtained by using line
      scan diffusion tensor imaging. METHODS: Diffusion tensor images in axial,
      coronal, and sagittal sections covering the entire brain volume were obtained
      with line scan diffusion imaging in six healthy volunteers. Images were acquired
      for b factors 5 and 1000 s/mm(2) at an imaging resolution of 1.7 x 1.7 x 4 mm.
      For selected regions, images were obtained at a reduced field of view with a
      spatial resolution of 0.9 x 0.9 x 3 mm. For each pixel, the direction of maximum
      diffusivity was computed and used to display the course of white matter fibers.
      RESULTS: Fiber directions derived from diffusion tensor imaging were consistent
      with known white matter fiber anatomy. The principal fiber tracts were well
      observed in all cases. The tracts that were visualized included the following:
      the arcuate fasciculus; superior and inferior longitudinal fasciculus; uncinate
      fasciculus; cingulum; external and extreme capsule; internal capsule; corona
      radiata; auditory and optic radiation; anterior commissure; corpus callosum;
      pyramidal tract; gracile and cuneatus fasciculus; medial longitudinal fasciculus;
      rubrospinal, tectospinal, central tegmental, and dorsal trigeminothalamic tract;
      superior, inferior, and middle cerebellar peduncle; pallidonigral and strionigral
      fibers; and root fibers of the oculomotor and trigeminal nerve. CONCLUSION: We
      obtained a complete set of detailed white matter fiber anatomy maps of the normal
      brain by means of line scan diffusion tensor imaging at high resolution. Near
      large bone structures, line scan produces images with minimal susceptibility
      artifacts.

PMID- 11827879
TI  - Depicting cerebral veins by three-dimensional CT angiography before surgical
      clipping of aneurysms.
AB  - BACKGROUND AND PURPOSE: Cerebral veins show wide variation, and unexpected veins
      occasionally limit surgical procedures for clipping of cerebral aneurysms. This
      study was undertaken to assess the utility of three-dimensional CT angiography
      (3D-CTA) in the evaluation of venous anatomy before surgical clipping of cerebral
      aneurysms. METHODS: 3D-CTA was performed in 19 patients before pterional
      craniotomy. The venous anatomy visualized by use of 3D-CTA was compared
      retrospectively with intraoperative findings. RESULTS: 3D-CTA clearly depicted
      the superficial sylvian veins (SSVs) in 17 of 19 cases. In three of these 17
      cases, 3D-CTA failed to reveal the additional connecting veins from SSVs to the
      midportion of the sphenoid wing. 3D-CTA also depicted bridging veins from: 1) the
      basal vein of Rosenthal to the sphenoparietal sinus (SPS) (three cases); 2) a
      junction of the anterior cerebral vein and the deep middle cerebral vein to the
      SPS (two cases); 3) the anterior cerebral vein into the cavernous sinus (one
      case); and 4) the deep middle cerebral vein to the cavernous sinus in one case.
      Surgical findings corresponded well with the angiographic findings. 3D-CTA
      depicted bridging veins from the frontal base into the SPS in two cases;
      retraction of the frontal lobe was severely limited in these cases. 3D-CTA also
      exhibited anatomic variation of deep cerebral veins, which suggests the utility
      of 3D-CTA in evaluating the risks carried by sacrifice of some bridging veins. In
      two patients, aneurysmal dissection was restricted because of adhering veins. 3D
      CTA depicted these cerebral veins to be lying in contact with the aneurysm. In
      one case, the contiguous vein was hidden behind a large middle cerebral artery
      aneurysm; 3D-CTA was helpful for visualization of this vein. CONCLUSION: 3D-CTA
      can clearly depict the venous anatomy of the brain and is useful for surgical
      planning of a pterional or temporopolar approach for cerebral aneurysms.

PMID- 11827880
TI  - Prospective evaluation of suspected stenoocclusive disease of the intracranial
      artery: combined MR angiography and CT angiography compared with digital
      subtraction angiography.
AB  - BACKGROUND AND PURPOSE: MR angiography is primarily and increasingly used to
      assess intracranial arterial stenoocclusion. However, MR angiography can cause
      overestimation of stenosis. Although CT angiography is accurate, it has
      limitations. Our purpose was to determine whether the accuracy of combined MR
      angiography and CT angiography is equal to that of digital subtraction
      angiography (DSA) in measuring stenosis and detecting major intracranial arterial
      occlusion. METHODS: CT angiography and intraarterial DSA were prospectively
      performed in 18 patients with suspected intracranial stenoocclusive disease, as
      revealed with MR angiography. Before DSA, two reviewers independently assessed MR
      intracranial angiograms. Subsequently, they assessed CT angiograms with MR
      angiograms. Results were compared with DSA results. The degree of stenoocclusion
      was categorized; stenosis of 50% or more indicated stenoocclusive disease. After
      the blinded study, two radiologists retrospectively reviewed the angiographic
      findings. RESULTS: Stenoocclusive disease was identified in 18 of 198
      intracranial arteries at DSA. MR angiography had a sensitivity of 92%, a
      specificity of 91%, and an accuracy of 91% for the identification of stenosis of
      50% or more; the addition of CT angiography yielded values of 100%, 99%, and 99%,
      respectively. Stenotic grades with combined CT angiography and MR angiography
      agreed with those of DSA in 98% of cases. In the retrospective study, CT
      angiography did not always correctly delineate arterial lumina with
      circumferential calcification and cavernous portions of the internal carotid
      artery. CONCLUSION: In this investigation, the evaluation of suspected
      stenoocclusive diseases in major intracranial arteries, the accuracy of combined
      MR angiography and CT angiography is equal to that of DSA in most cases.

PMID- 11827881
TI  - Radiology resident evaluation of head CT scan orders in the emergency department.
AB  - BACKGROUND AND PURPOSE: Prior studies have revealed little difference in
      residents' abilities to interpret cranial CT scans. The purpose of this study was
      to assess the performance of radiology residents at different levels of training
      in the interpretation of emergency head CT images. METHODS: Radiology residents
      prospectively interpreted 1324 consecutive head CT scans ordered in the emergency
      department at the University of Arizona Health Science Center. The residents
      completed a preliminary interpretation form that included their interpretation
      and confidence in that interpretation. One of five neuroradiologists with a
      Certificate of Added Qualification subsequently interpreted the images and
      classified their assessment of the residents' interpretations as follows:
      "agree," "disagree-insignificant," or "disagree-significant." The data were
      analyzed by using analysis-of-variance or chi-squared methods. RESULTS: Overall,
      the agreement rate was 91%; the insignificant disagreement rate, 7%; and the
      significant disagreement rate, 2%. The level of training had a significant (P
      =.032) effect on the rate of agreement; upper-level residents had higher rates of
      agreement than those of more junior residents. There were 62 false-negative
      findings. The most commonly missed findings were fractures (n = 18) and chronic
      ischemic foci (n = 12). The most common false-positive interpretations involved
      10 suspected intracranial hemorrhages and suspected fractures. CONCLUSION: The
      level of resident training has a significant effect on the rate of disagreement
      between the preliminary interpretations of emergency cranial CT scans by
      residents and the final interpretations by neuroradiologists. Efforts to reduce
      residents' errors should focus on the identification of fractures and signs of
      chronic ischemic change.

PMID- 11827882
TI  - Diffusion-weighted imaging and apparent diffusion coefficient maps in a case of
      intracerebral abscess with ventricular extension.
AB  - Previous findings have demonstrated the diagnostic usefulness of diffusion
      weighted imaging in depicting specific features of a brain abscess. We report a
      case of a cerebral abscess, which ruptured into the ventricular system, including
      its findings on both diffusion-weighted images and apparent diffusion coefficient
      (ADC) maps. Purulent material within the left lateral ventricle, similar to that
      of the central abscess cavity, was strongly hyperintense on diffusion-weighted
      images. However, variable signal intensity changes were observed on the ADC map;
      these probably corresponded to regional variation of the concentration of protein
      in the purulent material. In this case, both diffusion-weighted images and ADC
      maps were important and complementary in the evaluation of ventricular extension
      of an intracerebral abscess.

PMID- 11827883
TI  - Recanalization results after carotid stent placement.
AB  - BACKGROUND AND PURPOSE: The details of stent reconstruction in the vascular lumen
      and of the adaptation of carotid stents, the vessel wall, and the vascular
      anatomy are only occasionally reported. The purpose of this study was to
      determine the immediate and longer-term anatomic results after implantation of
      self-expanding carotid stents. METHODS: In a retrospective study, pre- and
      postprocedural angiograms and duplex sonograms from 40 consecutive carotid stent
      procedures in 39 patients (22 men, 17 women; mean age, 67 years; age range, 53-84
      years) with high-grade (> or =70 %) internal carotid artery (ICA) stenoses were
      evaluated to assess the expansion of the vascular lumen, apposition of the stent,
      and geometric changes in the ICA after the implantation of rolling-membrane and
      carotid Wallstents (n = 22) or Easy Wallstents (n = 18). RESULTS: Optimal
      widening of the lumen and apposition of the stent were achieved in 11 (28%) of 40
      arteries. Residual stenoses (n = 16), free stent filaments not attached to the
      vessel wall (n = 21), and stent-induced kinking of the ICA (n = 6) were minor
      shortcomings of stent reconstruction. Because of one death, peri-interventional
      morbidity and mortality rates were 3%. During follow-up (median, 24 months), one
      high-grade restenosis, one ipsilateral stroke, and two ipsilateral transient
      ischemic attacks were observed. CONCLUSION: Suboptimal anatomic results
      frequently occur after endovascular treatment of atherosclerotic carotid artery
      stenosis with self-expanding Wallstents. With the exception of one symptomatic
      restenosis, no major complications or longer-term sequelae were clearly related
      to these findings, but further controlled follow-up studies of larger samples are
      required.

PMID- 11827884
TI  - Oversizing of self-expanding stents: influence on the development of neointimal
      hyperplasia of the carotid artery in a canine model.
AB  - BACKGROUND AND PURPOSE: In carotid artery stent placement, marked oversizing of
      the stent relative to the internal carotid artery lumen is common. This study was
      performed to determine the influence of using oversized self-expanding nitinol
      stents on neointimal hyperplasia. METHODS: In six greyhound dogs, 24 self
      expanding nitinol stents (eight SMART stents, eight Easy Wallstents, eight Sinus
      Flex stents) were inserted into both common carotid arteries (CCAs). In each CCA,
      two stents were deployed; a stent of the appropriate diameter was implanted
      distally and an oversized stent proximally. After 4 months, transverse sections
      of each stent were examined histologically and at computerized image analysis.
      Neointimal hyperplasia was determined as the proportion of the residual diameter
      of the patent vessel lumen compared with the stent lumen. RESULTS: The amount of
      neointimal hyperplasia did not differ between the normal-sized and oversized
      stents. The mean preserved luminal diameter (+/-SEM) with normal- and oversized
      stents, respectively, were as follows: Easy Wallstent, 94% +/- 1.0 and 96% +/-
      1.5; SMART stent, 92% +/- 1.6 and 93% +/- 1.8; and Sinus-Flex stent, 93% +/- 2.7
      and 93% +/- 2.6. The mean preserved patent lumen with the 12 normal-sized stents
      (93% +/-1.0) was not significantly different from that of the 12 oversized stents
      (94% +/- 1.1, P =.502). CONCLUSION: Under experimental conditions, use of self
      expanding stents oversized by 30-40% appeared to result in neointimal hyperplasia
      comparable to that caused by normal-sized stents. All three stent types appeared
      to have similarly low neointimal responses.

PMID- 11827885
TI  - Cyanoacrylate embolization of experimental aneurysms.
AB  - BACKGROUND AND PURPOSE: Cyanoacrylates are effective occlusive agents in
      neurovascular interventions. To study their potential to improve long-term
      results of endovascular treatment of aneurysms, we conducted experimental studies
      in canine aneurysm models. METHODS: Venous pouch carotid aneurysms were
      constructed in dogs. Results of coil embolization of lateral wall and bifurcation
      aneurysms were compared. A lateral wall model of embolization with gelatin
      sponges was used to study the effects of coating sponges with cyanoacrylate on
      angiographic results and neointima thickness at 3 and 12 weeks. These models were
      also used to investigate the control of endovascular cyanoacrylate deposition,
      alone or over a coil placed at the neck of the treated lesions. The results of
      endovascular cyanoacrylate embolization of bifurcation aneurysms were compared
      with those of coil embolization at 3 months. RESULTS: Bifurcation aneurysms
      treated with coils showed more frequent recurrences (P <.01) and thinner
      neointimas (P <.01) at 3 months than did lateral wall aneurysms. Cyanoacrylate
      coated sponges improved angiographic results (P <.05) and led to thicker
      neointimas at 3 and 12 weeks (P <.05) as compared with uncoated sponges.
      Endovascular cyanoacrylate deposition with microcatheters led to stray emboli in
      all cases. Cyanoacrylate delivery was improved by a single coil positioned at the
      neck of the aneurysm, but parent vessel embolization still occurred in 25% of the
      animals. Cyanoacrylate embolization of bifurcation aneurysms improved
      angiographic results at 3 months as compared with coil embolization (P <.01).
      CONCLUSION: Cyanoacrylate embolization is currently difficult to control. It has
      the potential to decrease recurrences after endovacular treatment of aneurysms,
      but a safe method for endovascular delivery has yet to be developed.

PMID- 11827886
TI  - Appropriate interval between embolization and surgery in patients with
      meningioma.
AB  - BACKGROUND AND PURPOSE: The best time for surgery after embolization of
      meningiomas remains unclear. We used the tumor-softening effect of embolization
      to determine this time. METHODS: Forty-two patients with intracranial meningiomas
      that received more than 50% of their blood supply from the external carotid
      artery underwent embolization before surgery. The interval between embolization
      and surgery and the tumor consistency at the time of surgery were recorded. The
      interval between embolization and surgery was divided into 3-day segments, and an
      average tumor consistency score was obtained in segments. Patients were assigned
      to two groups: group 1 underwent surgery on a specified day after embolization;
      group 2 underwent surgery at a later date. We compared tumor consistency, blood
      loss, length of hospitalization, surgical resection time, Simpson grade at
      surgery, and complication rate in both groups. RESULTS: On the polynomial
      regression curve, greatest tumor softening occurred 7-9 days after embolization.
      When the postembolization interval exceeded 10 days, no further softening
      occurred. Compared with group 1 patients, group 2 patients did not have an
      increased blood loss, a longer hospitalization, or a higher complication rate. In
      group 2, the surgical procedure required less time, and the Simpson grades were
      lower. CONCLUSION: In meningiomas that receive more than 50% of their blood
      supply from the external carotid artery, the optimal interval between
      embolization and surgery is 7-9 days. This interval allows the greatest degree of
      tumor softening, which makes it possible to remove the tumor more safely and
      easily.

PMID- 11827887
TI  - Analysis of the cerebral cortex in holoprosencephaly with attention to the
      sylvian fissures.
AB  - BACKGROUND AND PURPOSE: Analysis of specific features in the brain of patients
      with holoprosencephaly (HPE) may clarify normal and abnormal brain development
      and help predict outcomes for specific children. We assessed sulcal and gyral
      patterns of cerebral cortex in patients with HPE and developed a method of
      grading brain development. METHODS: Neuroimaging studies (75 MR imaging, 21 CT)
      of 96 patients with HPE were retrospectively reviewed, with specific attention
      paid to the cerebral cortex. Thickness of cortex, width of gyri, and depth of
      sulci were assessed subjectively and by measurement. The angle between lines
      drawn tangential to the sylvian fissures ("sylvian angle") was measured in each
      patient with HPE and in 20 control patients. RESULTS: Thickness of cortex was
      normal in all 96 patients. Gyral shape and width and sulcal depth were normal in
      80 patients. Twelve patients, all with very severe HPE and microcephaly, had
      reduced sulcal depth, diffusely in eight and limited to the anteromedial cortex
      in four with lobar HPE. Four patients had subcortical heterotopia, located
      anterior to the interhemispheric fissure, associated with shallow sulci in the
      overlying cortex. Sylvian fissures were displaced further anteriorly and medially
      as HPE became more severe, until, in the most severe cases, no sylvian fissures
      could be identified. Sylvian angle measurements corresponded closely with
      severity of HPE, being largest in the most severe and smallest in the least
      severe cases. All patients with HPE had sylvian angles significantly larger than
      the mean of 15 degrees measured in the control patients. CONCLUSION: The only
      true malformations of cortical development were subcortical heterotopia. However,
      diffuse and focal abnormal sulci were observed. We propose our sylvian angle
      measurement of extent of frontal lobe development as an objective means of
      quantifying the severity of HPE.

PMID- 11827888
TI  - The middle interhemispheric variant of holoprosencephaly.
AB  - BACKGROUND AND PURPOSE: The middle interhemispheric variant of holoprosencephaly
      (MIH) is a rare malformation in which the cerebral hemispheres fail to divide in
      the posterior frontal and parietal regions. We herein describe the structural
      abnormalities of the brain in a large group of patients with MIH, compare these
      features with those of classic holoprosencephaly (HPE), and propose a
      developmental mechanism, based on current knowledge of developmental
      neurogenetics, by which MIH develops. METHODS: Brain images obtained in 21
      patients with MIH (MR images in 16 patients and high-quality X-ray CT scans in
      five patients) were retrospectively reviewed to classify cerebral abnormalities.
      The cerebral parenchyma, hypothalami, caudate nuclei, lentiform nuclei, thalami,
      and mesencephalon were examined for the degree of midline separation (cleavage)
      of the two hemispheres. The orbits, olfactory apparati, and presence or absence
      of a dorsal cyst were also assessed. RESULTS: In all patients, by definition,
      midportions of the cerebral hemispheres were continuous across the midline, with
      an intervening interhemispheric fissure. The sylvian fissures were abnormally
      connected across the midline over the vertex in 18 (86%) of 21 patients. Two
      patients had relatively normal-appearing sylvian fissures; one had unilateral
      absence of a sylvian fissure owing to substantial subcortical heterotopia.
      Heterotopic gray matter or dysplastic cerebral cortex was also seen in 18 (86%)
      of 21 patients. MIH differed from classic HPE as follows. 1) In all subjects, the
      midline third ventricle separated the hypothalamus and lentiform nuclei. 2) The
      caudate nuclei were separated by the cerebral ventricles in 17 (89%) of the 19
      [corrected] patients in whom they could be assessed. 3) The most commonly
      affected basal nucleus was the thalamus (non-cleavage in seven [33%] of 21 cases,
      abnormal alignment in 1 [5%]). 4) Three (18%) of the 17 [corrected] patients in
      whom the mesencephalon could be assessed showed some degree of mesencephalic non
      cleavage. 5) No patients had hypotelorism (four had hypertelorism, the remainder
      manifested normal intraocular distances). Dorsal cysts were present in five (25%)
      of the 20 patients in whom they could be assessed (dorsal cysts could not be
      assessed after shunt surgery), and as in classic HPE, were associated with severe
      thalamic non-cleavage in three of these five patients. CONCLUSION: MIH appears to
      cause non-cleavage of midline structures in a completely different pattern than
      does classic HPE. In MIH, impaired induction or expression of genetic factors
      appears to influence the embryonic roof plate, whereas in classic HPE, induction
      or expression of the embryonic floor plate seems to be affected.

PMID- 11827889
TI  - MR evaluation in patients with isolated anosmia since birth or early childhood.
AB  - BACKGROUND AND PURPOSE: Anosmias with chromosomal disorders has been well
      investigated. However, isolated anosmia (IA) has received less attention,
      although it occurs more frequently. We compared frontobasal structures in
      patients with IA since birth or early childhood with those in control subjects.
      METHODS: Imaging findings obtained in 16 patients with IA were compared with
      those obtained in eight control subjects. Imaging was performed with a standard
      quadrature head coil at 1.5 T. T1-weighted spin-echo (coronal plane perpendicular
      to frontal skull base; section thickness, 3 mm; pixels, 0.43 x 0.39 mm) and
      sagittal T1-weighted magnetization-prepared rapid gradient-echo (voxels, 1.0 x
      1.0 x 1.0 mm) sequences were performed. We assessed the length and depth of the
      olfactory sulcus, olfactory bulb volume, and olfactory sulcus depth in the plane
      of the posterior tangent through the eyeballs (PPTE). RESULTS: Five patients with
      IA had bilateral hypoplastic olfactory bulbs. Three patients with IA had
      hypoplastic olfactory bulbs on the right and aplastic olfactory bulbs on the
      left. Eight patients with IA had bilaterally aplastic olfactory bulbs. The depth
      of the olfactory sulcus at the level of the PPTE was smaller in patients with IA
      than in control subjects. The depth of the olfactory sulcus was greater on the
      right than on the left, and there was no overlap. Among patients with IA, the
      depth of the olfactory sulcus differed significantly between those with and those
      without visible olfactory tracts. CONCLUSION: The depth of the olfactory sulcus
      at the level of the PPTE reflects the presence of olfactory tracts. The presence
      or absence of the olfactory tract may therefore have some association with
      cortical growth of the olfactory sulcus region. The olfactory sulcus is deeper on
      the right than on the left, particularly in patients with IA. We speculate that
      olfaction may be processed predominantly in the right hemisphere.

PMID- 11827890
TI  - Characterization of benign and metastatic vertebral compression fractures with
      quantitative diffusion MR imaging.
AB  - BACKGROUND AND PURPOSE: Conventional imaging techniques cannot be used to
      unambiguously and reliably differentiate malignant from benign vertebral
      compression fractures. Our hypothesis is that these malignant and benign
      vertebral lesions can be better distinguished on the basis of tissue apparent
      diffusion coefficients (ADCs). The purpose of this study was to test this
      hypothesis by using a quantitative diffusion imaging technique. METHODS: Twenty
      seven patients with known cancer and suspected metastatic vertebral lesions
      underwent 1.5-T conventional T1-weighted, T2-weighted, and contrast-enhanced T1
      weighted imaging to identify the lesions. Diffusion-weighted images of the areas
      of interest were acquired by using a fast spin-echo diffusion pulse sequence with
      b values of 0-250 s/mm(2). The abnormal regions on the diffusion-weighted images
      were outlined by using the conventional images as guides, and the ADC values were
      calculated. On the basis of pathologic results and clinical findings, the cases
      were divided into two categories: benign compression fractures and metastatic
      lesions. The ADC values for each category were combined and plotted as
      histograms; this procedure was followed by statistical analysis. RESULTS: The
      patient group had 12 benign fractures and 15 metastases. The mean ADC values, as
      obtained from the histograms, were (1.9 +/- 0.3) x 10(-4) mm(2)/s and (3.2 +/-
      0.5) x 10(-4) mm(2)/s for metastases and benign fractures, respectively.
      CONCLUSION: Our results indicate that quantitative ADC mapping, instead of
      qualitative diffusion-weighted imaging, can provide valuable information in
      differentiating benign vertebral fractures from metastatic lesions.

PMID- 11827891
TI  - Recurrent neurovascular hypertension.

PMID- 11827892
TI  - Spinal cord involvement in CNS Whipple disease: an ongoing experience in the MR
      imaging era.

PMID- 11827893
TI  - Thallium-201 single-photon emission CT in recurrent squamous cell carcinoma of
      the head and neck.

PMID- 11827894
TI  - Atraumatic lumbar puncture.

PMID- 11827895
TI  - Cochrane's epitaph for cisapride in childhood gastro-oesophageal reflux.

PMID- 11827896
TI  - Optimisation of thyroxine dose in congenital hypothyroidism.

PMID- 11827897
TI  - Religious circumcision and the Human Rights Act.

PMID- 11827898
TI  - The health effects of fossil fuel derived particles.
AB  - Over the past 10 years there has been increasing evidence that particles
      generated by the combustion of fossil fuels adversely affect health. To what
      extent should paediatricians be concerned about particle pollution? This review
      assesses what we know, and what we still need to know about the health effects of
      fossil fuel particles.

PMID- 11827899
TI  - Effects of cognitive, motor, and sensory disabilities on survival in cerebral
      palsy.
AB  - BACKGROUND: Cerebral palsy presents with a range of severity of cognitive, motor,
      and sensory disabilities, which might affect survival. AIMS: To quantify the
      effects of motor, cognitive, and sensory disabilities, year of birth, birth
      weight, and gestational age on survival in cerebral palsy. METHODS: A cohort of
      children with cerebral palsy born between 1966 and 1989 to mothers resident in a
      defined geographical region was subdivided into early impairment (EICP: cerebral
      insult prenatally or within 28 days of birth) or late impairment (LICP: insult at
      least 28 days after birth). Deaths are notified by the National Health Service
      Central Register. Birth and disability details were obtained from clinical
      records. Survival analyses were carried out. RESULTS: Severe motor disability was
      associated with a 30 year survival of 42% and severe cognitive disability with a
      30 year survival of 62%. Severe visual disability was associated with a 30 year
      survival of 38%, but the association of survival with hearing disability was
      weak. EICP had better survival than LICP but the difference was not significant
      after allowing for severity of functional disabilities. Normal birth weight
      infants (>/= 2500 g) showed no birth cohort effect, but the 10 year survival of
      low birth weight (<2500 g) infants declined from 97% for 1966 to 89% for 1989
      births. CONCLUSIONS: Survival in cerebral palsy varies according to the severity
      and number of functional disabilities and by birth weight. Among low birth weight
      children, survival declined steadily from 1966 to 1989 after allowing for
      disability. The disabilities reported do not capture all the factors affecting
      survival of preterm infants.

PMID- 11827900
TI  - Primary school accident reporting in one education authority.
AB  - BACKGROUND: Studies have shown a correlation between increased accident rates and
      levels of deprivation in the community. School accident reporting is one area
      where an association might be expected. AIMS: To investigate differences in
      primary school accident rates in deprived and more affluent wards, in an area
      managed by one education authority. METHODS: Statistical analysis of accident
      form returns for 100 primary schools in one education authority in Wales over a
      two year period, in conjunction with visits to over one third of school sites.
      RESULTS: Accident report rates from schools in deprived wards were three times
      higher than those from schools in more affluent wards. School visits showed that
      this discrepancy was attributable primarily to differences in reporting
      procedures. One third of schools did not report accidents and approximately half
      did not keep records of minor accidents. CONCLUSIONS: The association between
      school accident report rates and deprivation in the community is complex. School
      accident data from local education authorities may be unreliable for most
      purposes of collection.

PMID- 11827901
TI  - Family cognitive behaviour therapy for chronic fatigue syndrome: an uncontrolled
      study.
AB  - AIM: To examine the efficacy of family focused cognitive behaviour therapy for 11
      18 year olds with chronic fatigue syndrome. METHODS: Twenty three patients were
      offered family focused cognitive behaviour therapy. The main outcome was a
      fatigue score of less than 4 and attendance at school 75% of the time. RESULTS:
      Twenty patients completed treatment. Eighteen had completed all measures at six
      months follow up; 15 of these (83%) improved according to our predetermined
      criterion. Substantial improvements in social adjustment, depression, and fear
      were noted. CONCLUSIONS: Family focused cognitive behaviour therapy was effective
      in improving functioning and reducing fatigue in 11-18 year olds. Gains were
      maintained at six months follow up.

PMID- 11827902
TI  - Investigating subdural haemorrhage in infants.
AB  - When an infant or young child presents with subdural haemorrhage, the diagnostic
      priority is to exclude physical child abuse. A team approach should be adopted
      for the clinical child protection investigation. The diagnostic process is
      inevitably one of detective work; appropriate radiological, ophthalmological,
      haematological, biochemical, and postmortem investigations are discussed.

PMID- 11827903
TI  - Critical illness neuromuscular disease: clinical, electrophysiological, and
      prognostic aspects.
AB  - BACKGROUND: Critical illness neuromuscular disease, which has been recognised as
      a distinct clinical entity in adults, remains poorly described in children. AIMS:
      To assess retrospectively the clinical, electrophysiological, and prognostic
      features of the disease. METHODS: Retrospective study in a children's university
      hospital. RESULTS: Five critically ill patients presented with generalised
      paralysis, associated with long lasting failure to breathe in three. The cause of
      the generalised paralysis was critical illness neuropathy in two, acute myopathy
      in two, and mixed neuromyopathy in one. CONCLUSIONS: Neuromuscular disease should
      be suspected in critically ill children with muscle weakness. Because
      corticosteroids and muscle relaxants appear to trigger some types of intensive
      care unit neuromuscular disease in children, their use should be restricted or
      administered at the lowest doses possible.

PMID- 11827904
TI  - Hypoxaemia in acute respiratory and non-respiratory illnesses in neonates and
      children in a developing country.
AB  - AIMS: To determine, in sick neonates and children requiring admission to a
      hospital in the highlands of Papua New Guinea: (1) the incidence and severity of
      hypoxaemia; (2) the proportion with hypoxaemia who do not fulfil criteria for
      acute lower respiratory infection (ALRI); and (3) the power of clinical signs to
      predict hypoxaemia, according to age and disease category. METHODS: Age dependent
      normal values for transcutaneous oxygen saturation (SpO(2)) were established in
      218 well neonates and children in Goroka. A total of 491 sick neonates and
      children were then studied on presentation to the paediatric department at Goroka
      Hospital. RESULTS: A total of 257 sick neonates and children (52%) were
      hypoxaemic. Hypoxaemia was present in 179/245 (73%) with clinical criteria for
      ALRI; 79/246 (32%) with non-ALRI illnesses (including meningitis, septicaemia,
      severe malnutrition, low birth weight, birth asphyxia, and congenital syphilis)
      were also hypoxaemic. For children aged 1 month to 5 years with ALRI, the
      clinical signs best predicting hypoxaemia were cyanosis, respiratory rate >60,
      poor feeding, or reduced spontaneous activity; in those without ALRI the best
      predictors were cyanosis, respiratory rate >60 per minute, and inability to feed,
      but the positive predictive value was much lower than for children with ALRI. For
      neonates cyanosis was predictive of hypoxaemia, but tachypnoea or inability to
      feed were not. CONCLUSIONS: Hypoxaemia is an under recognised complication of non
      ALRI illnesses in children and in sick neonates in developing countries. Use of
      algorithms with high sensitivity for the recognition of hypoxaemia, and protocols
      for administration of oxygen to neonates, and to children with non-ALRI
      illnesses, might substantially reduce case fatality.

PMID- 11827905
TI  - Clinical efficacy of co-trimoxazole versus amoxicillin twice daily for treatment
      of pneumonia: a randomised controlled clinical trial in Pakistan.
AB  - AIMS: To compare the clinical efficacy of twice daily oral co-trimoxazole with
      twice daily oral amoxicillin for treatment of childhood pneumonia. METHODS:
      Randomised controlled, double blind, multicentre study in outpatient departments
      of seven hospitals and in one community health service. A total of 1471 children
      (aged 2-59 months) with non-severe pneumonia were randomly assigned to 25 mg/kg
      amoxicillin (n = 730) or 4 mg/kg trimethoprim plus 20 mg/kg sulphamethoxazole (co
      trimoxazole) (n = 741). Both medicines were given orally twice daily for five
      days. RESULTS: Data from 1459 children were analysed: 725 were randomised to
      amoxicillin and 734 to co-trimoxazole. Treatment failure in the amoxicillin group
      was 16.1% compared to 18.9% in the co-trimoxazole group. Multivariate analysis
      showed that treatment failure was more likely in infants who had history of
      difficult breathing or those who had been ill for more than three days before
      presentation. CONCLUSIONS: Both amoxicillin and co-trimoxazole were equally
      effective in non-severe pneumonia. Good follow up of patients is essential to
      prevent worsening of illness.

PMID- 11827906
TI  - Impact of antiretroviral protocols on dynamics of AIDS progression markers.
AB  - AIMS: To assess the "real life" effectiveness of different antiretroviral
      therapies (ART). METHODS: A retrospective multicentre observational study in 150
      HIV-1 vertically infected children on the progression to AIDS (study A), and in
      61 HIV-1 infected children on the evolution of the most relevant markers of
      progression (study B). All children were categorised into four groups: untreated
      (NT); on monotherapy (MT); on combination therapy (dual-ART); and on potent ART
      (HAART). RESULTS: No child in the HAART group progressed to AIDS, whereas 14
      children in the NT and seven in the MT groups progressed to AIDS, respectively,
      the differences being statistically significant. There was a mean increase of 8
      units of %CD4+ per year; this was greater in the HAART group than in the other
      groups. The mean decrease in viral load was 0.65 log(10) copies/ml per year; this
      was greater in the HAART group than in the NT and MT groups. The HAART group had
      the lowest probability of returning to baseline %CD4+ and viral load. CONCLUSION:
      Potent ART had the greatest protective effect against progression to AIDS in this
      observational study.

PMID- 11827907
TI  - Febrile convulsions and sudden infant death syndrome.
AB  - It has been suggested that sudden infant death syndrome (SIDS) and febrile
      convulsions are related aetiologically. We compared the risk of SIDS in 9877
      siblings of children who had had febrile convulsions with that of 20 177 siblings
      of children who had never had febrile convulsions. We found no support for the
      shared susceptibility hypothesis.

PMID- 11827908
TI  - Selective renal embolisation for renovascular hypertension?
AB  - An 11 year old girl developed hypertensive encephalopathy and renal failure from
      reflux nephropathy. Resection of her shrunken left kidney did not control her
      hypertension. Two selective arterial embolisations of the scarred right lower
      pole produced only transient benefit, but a heminephrectomy gave good control.
      Embolisation may delay definitive treatment.

PMID- 11827909
TI  - Acute ataxia complicating Langherans cell histiocytosis.
AB  - A case is reported of a 3 year old boy with an acute history of cerebellar
      impairment and x ray evidence of apparent chest infection. At postmortem
      examination, his lungs but not the nervous system were found to be massively
      infiltrated by Langherans histiocytes. In retrospect, the acute ataxia was
      diagnosed as a paraneoplastic phenomenon secondary to Langherans cell
      histiocytosis (LCH). This represents a unique occurrence complicating LCH in
      childhood.

PMID- 11827910
TI  - Primary antiphospholipid syndrome presenting as complicated Henoch-Schonlein
      purpura.
AB  - A child showing signs of Henoch-Schonlein purpura developed a right tibiofibular
      vascular thrombosis. Antiphospholipid antibody tests were positive for both lupus
      anticoagulant and anticardiolipin antibodies. This suggests that an
      antiphospholipid syndrome should be considered in cases of Henoch-Schonlein
      purpura and antiphospholipid antibodies should be measured to determine whether
      prophylactic antithrombotic measures are needed to prevent thrombotic
      manifestations.

PMID- 11827912
TI  - An evidence and consensus based guideline for acute diarrhoea management.

PMID- 11827911
TI  - Limitations and uses of gastrojejunal feeding tubes.
AB  - BACKGROUND: Gastrostomy feeding is a well established alternative method to long
      term nasogastric tube feeding. Many such patients have gastro-oesophageal reflux
      (GOR) and require a fundoplication. A transgastric jejunal tube is an alternative
      when antireflux surgery fails, or is hazardous or inappropriate. AIMS: To review
      experience of gastrojejunal (G-J) feeding over six years in two regional centres
      in the UK. METHODS: Retrospective review of all children who underwent insertion
      of a G-J feeding tube. RESULTS: There were 18 children, 12 of whom were
      neurologically impaired. G-J tubes were inserted at a median age of 3.1 years
      (range 0.6-14.7) because of persistent symptoms after Nissen fundoplication (n =
      8) or symptomatic GOR where fundoplication was inappropriate. Four underwent
      primary endoscopic insertion of the G-J tube; the remainder had the tube inserted
      via a previous gastrostomy track. Seventeen showed good weight gain. There was
      one insertion related complication. During a median follow up of 10 months (range
      1-60), four experienced recurrent aspiration, bilious aspirates, and/or
      diarrhoea. There were 65 tube related complications in 14 patients, necessitating
      change of the tube at a median of 74 days. Jejunal tube migration was the
      commonest problem. Five died from complications of their underlying disease.
      CONCLUSIONS: Although G-J feeding tubes were inserted safely and improved
      nutritional status, their use was associated with a high rate of morbidity.
      Surgical alternatives such as an Roux-en-Y jejunostomy may be preferable.

PMID- 11827913
TI  - Parental smoking.

PMID- 11827916
TI  - Fundamentals of endothelial function for the clinical cardiologist.

PMID- 11827917
TI  - Angiographical follow-up after radioactive "Cold Ends" stent implantation: a
      multicenter trial.
AB  - BACKGROUND: Radioactive stents with an activity of 0.75 to 12 microCi have shown
      >40% edge restenosis due to neointimal hyperplasia and negative remodeling. This
      trial evaluated whether radioactive Cold Ends stents might resolve edge
      restenosis by preventing remodeling at the injured extremities. METHODS AND
      RESULTS: The 25-mm long (15-mm radioactive center and 5-mm nonradioactive ends)
      Cold Ends stents had an activity of 3 to 12 microCi at implantation. Forty-three
      stents were implanted in 43 patients with de novo native coronary artery disease.
      Two procedural, 1 subacute, and 1 late stent thrombosis occurred. A restenosis
      rate of 22% was observed with a shift of the restenosis, usually occurring at the
      stent edges of radioactive stents, into the Cold Ends stents. The most severe
      restenosis occurred at the transition zone from radioactive to nonradioactive
      segments, a region located in dose fall-off. CONCLUSION: Cold Ends stents did not
      resolve edge restenosis.

PMID- 11827918
TI  - Minor myocardial damage and prognosis: are spontaneous and percutaneous coronary
      intervention-related events different?
AB  - BACKGROUND: The relevance of the adverse prognostic implications of CK-MB
      elevation after percutaneous coronary intervention (PCI) remains controversial.
      Therefore, we compared the relationship between the level of postprocedural CK-MB
      elevation and 6-month mortality in patients undergoing PCI with the relationship
      between the level of spontaneous, non-PCI-related CK-MB elevation and 6-month
      mortality in patients with acute coronary syndromes (ACS) treated medically.
      METHODS AND RESULTS: In the PURSUIT trial, 5583 of 9461 patients who presented
      with a non-ST-elevation ACS did not undergo PCI or CABG and had at least 1 CK-MB
      sample collected during index-hospitalization. There was a gradual increase in 6
      month mortality with higher CK-MB levels: 4.1%, 8.6%, 9.0%, 14.3%, 15.5% for CK
      MB ratios 0 to 1, >1 to 3, >3 to 5, >5 to 10, and >10 times the upper limit of
      normal. A combined analysis in 8838 patients undergoing PCI in 5 large, clinical
      trials revealed a proportional relationship between postprocedural CK-MB levels
      (</= 48 hours after PCI) and 6-month mortality. In patients with CK-MB ratios 0
      to 1, >1 to 3, >3 to 5, >5 to 10, and >10, the risk of death was 1.3%, 2.0%,
      2.3%, 4.3%, and 7.4%, respectively. The absolute mortality rates were lower after
      procedure-related infarcts compared with spontaneous infarcts. Yet, the relative
      increase in 6-month mortality with each increase in peak CK-MB level was similar
      for PCI-related myocardial necrosis and spontaneous myocardial necrosis, as all
      tests for heterogeneity of the odds ratios were nonsignificant. CONCLUSIONS: The
      present analysis indicates that the adverse prognostic implications of
      periprocedural myocardial necrosis should be considered similar to the adverse
      consequences of spontaneous myocardial necrosis.

PMID- 11827919
TI  - Department of Veterans Affairs Cooperative Studies Program Clinical Trial
      comparing combined warfarin and aspirin with aspirin alone in survivors of acute
      myocardial infarction: primary results of the CHAMP study.
AB  - BACKGROUND: Both aspirin and warfarin when used alone are effective in the
      secondary prevention of vascular events and death after acute myocardial
      infarction. We tested the hypothesis that aspirin and warfarin therapy, when
      combined, would be more effective than aspirin monotherapy. Methods and Results-
      We conducted a randomized open-label study to compare the efficacy of warfarin
      (target international normalized ratio 1.5 to 2.5 IU) plus aspirin (81 mg daily)
      with the efficacy of aspirin monotherapy (162 mg daily) in reducing the total
      mortality in 5059 patients enrolled within 14 days of infarction and followed for
      a median of 2.7 years. Secondary end points included recurrent myocardial
      infarction, stroke, and major hemorrhage. Four hundred thirty-eight (17.3%) of
      2537 patients assigned to the aspirin group and 444 (17.6%) of 2522 patients
      assigned to the combination group died (log-rank P=0.76). Recurrent myocardial
      infarction occurred in 333 patients (13.1%) taking aspirin and in 336 patients
      (13.3%) taking combination therapy (log-rank P=0.78). Stroke occurred in 89
      patients (3.5%) taking aspirin and in 79 patients (3.1%) taking combination
      therapy (log-rank P=0.52). Major bleeding occurred more frequently in the
      combination therapy group than in the aspirin group (1.28 versus 0.72 events per
      100 person years of follow-up, respectively; P<0.001). There were 14 individuals
      with intracranial bleeds in both the aspirin and combination therapy groups.
      CONCLUSIONS: In post-myocardial infarction patients, warfarin therapy (at a mean
      international normalized ratio of 1.8) combined with low-dose aspirin did not
      provide a clinical benefit beyond that achievable with aspirin monotherapy.

PMID- 11827920
TI  - Weight loss reduces C-reactive protein levels in obese postmenopausal women.
AB  - BACKGROUND: C-reactive protein (CRP) has been proposed as an independent risk
      factor for cardiovascular disease and has been positively associated with body
      weight and body fatness. We examined the hypothesis that weight loss would reduce
      plasma CRP levels in obese postmenopausal women. METHODS AND RESULTS: In a sample
      of 61 obese (body mass index, 35.6 +/- 5.0 kg/m(2)), postmenopausal women (age,
      56.4 +/- 5.2 years), we found that plasma CRP levels were positively associated
      with dual x-ray absorptiometry-measured total body fatness (r=0.36, P<0.005) and
      CT-measured intra-abdominal body fat area (r=0.30, P<0.02). Significant
      correlations were also found between plasma CRP and triglyceride levels (r=0.33,
      P<0.009) and glucose disposal measured by the hyperinsulinemic-euglycemic clamp
      technique (r=-0.29, P<0.03). Twenty-five of the 61 women tested at baseline
      completed a weight loss protocol. The average weight loss was 14.5 +/- 6.2 kg (
      15.6%, P<0.0001), with losses of 10.4 +/- 5.4 kg fat mass (-25.0%, P<0.0001) and
      2.8 +/- 1.4 kg fat-free mass (-6.0%, P<0.0001). Visceral and subcutaneous fat
      areas were reduced by -36.4% and -23.7%, respectively (P<0.0001). Plasma CRP
      levels were significantly reduced by weight loss: average -32.3%, from 3.06
      (+0.69, -1.29) to 1.63 (+0.70, -0.75) microgram/mL (P<0.0001, medians and
      interquartile differences). Changes in body weight and in total body fat mass
      were both positively associated with plasma CRP level reductions. CONCLUSIONS:
      Adiposity was a significant predictor of plasma CRP in postmenopausal women on a
      cross-sectional basis. Moreover, caloric restriction-induced weight loss
      decreased plasma CRP levels. Weight loss may represent an important intervention
      to reduce CRP levels, which may mediate part of its cardioprotective effects in
      obese postmenopausal women.

PMID- 11827922
TI  - Insulin causes endothelial dysfunction in humans: sites and mechanisms.
AB  - BACKGROUND: Insulin resistance is often accompanied by hyperinsulinemia and may
      predispose to atherosclerosis. Endothelium plays a central role in atherogenesis.
      The in vivo effects of hyperinsulinemia on endothelial function of large conduit
      arteries are unknown. METHODS AND RESULTS: Twenty-five healthy subjects were
      enrolled for study. In study A (n=9), subjects underwent both a time-control
      saline study and a euglycemic low-dose insulin (insulin approximately 110 pmol/L)
      clamp for 6 hours. Study B (n=5) was identical to study A except that the
      euglycemic clamp was performed at high physiological insulin concentrations
      (approximately 440 pmol/L). In study C (n=7), subjects underwent two 4-hour
      euglycemic insulin (approximately 110 pmol/L) clamps with and without the
      concomitant infusion of an antioxidant (vitamin C). In study D (n=4), two saline
      time-control studies were performed with and without the concomitant infusion of
      vitamin C. In all studies, both at baseline and throughout the experimental
      period, endothelium-dependent (flow-mediated) and endothelium-independent
      (nitroglycerin-induced) vasodilation was assessed in femoral and brachial
      arteries by echo Doppler. Both low (study A) and high physiological (study B)
      hyperinsulinemia abolished endothelium-dependent vasodilation, whereas
      endothelium-independent vasodilation was unaffected. Vitamin C fully restored
      insulin-impaired endothelial function without affecting endothelium-independent
      vasodilation (study C). Vitamin C had no effects on endothelium-dependent or
      endothelium-independent vasodilation during saline control studies (study D).
      CONCLUSIONS: Modest hyperinsulinemia, mimicking fasting hyperinsulinemia of
      insulin-resistant states, abrogates endothelium-dependent vasodilation in large
      conduit arteries, probably by increasing oxidant stress. These data may provide a
      novel pathophysiological basis to the epidemiological link between
      hyperinsulinemia/insulin-resistance and atherosclerosis in humans.

PMID- 11827921
TI  - T-cell-mediated lysis of endothelial cells in acute coronary syndromes.
AB  - BACKGROUND: CD4 T lymphocytes accumulate in unstable plaque. The direct and
      indirect involvement of these T cells in tissue injury and plaque instability is
      not understood. METHODS AND RESULTS: Gene profiling identified perforin, CD161,
      and members of the killer-cell immunoglobulin-like receptors as being
      differentially expressed in CD4(+)CD28(null) T cells, a T-cell subset that
      preferentially infiltrates unstable plaque. Frequencies of CD161(+) and perforin
      expressing CD4 T cells in peripheral blood were significantly increased in
      patients with unstable angina (UA). CD161 appeared on CD4(+)CD28(null) T cells
      after stimulation, suggesting spontaneous activation of circulating CD4 T cells
      in UA. Perforin-expressing CD4(+) T-cell clones from patients with UA exhibited
      cytotoxic activity against human umbilical vein endothelial cells (HUVECs) in
      redirected cytotoxicity assays after T-cell receptor triggering and also after
      stimulation of major histocompatibility complex class I-recognizing killer-cell
      immunoglobulin-like receptors. HUVEC cytolysis was dependent on granule
      exocytosis, as demonstrated by the paralyzing effect of pretreating
      CD4(+)CD28(null) T cells with strontium. Incubation of HUVECs with C-reactive
      protein (CRP) increased HUVEC lysis in a dose-dependent fashion. CONCLUSIONS: In
      patients with UA, CD4 T cells undergo a change in functional profile and acquire
      cytotoxic capability. Cytotoxic CD4 T cells effectively kill endothelial cells;
      CRP sensitizes endothelial cells to the cytotoxic process. We propose that T-cell
      mediated endothelial cell injury is a novel pathway of tissue damage that
      contributes to plaque destabilization. The sensitizing effect of CRP suggests
      synergy between dysregulated T-cell function and acute phase proteins in acute
      coronary syndromes.

PMID- 11827923
TI  - Rotational atherectomy does not reduce recurrent in-stent restenosis: results of
      the angioplasty versus rotational atherectomy for treatment of diffuse in-stent
      restenosis trial (ARTIST).
AB  - BACKGROUND: Aim of this trial was to compare rotational atherectomy followed by
      balloon angioplasty (rotablation [ROTA] group) with balloon angioplasty
      (percutaneous transluminal coronary angioplasty [PTCA] group) alone in patients
      with diffuse in-stent restenosis. METHODS AND RESULTS: The ARTIST study is a
      multicenter, randomized, prospective European trial with 298 patients with in
      stent restenosis>70% (mean lesion length, 14 +/- 8 mm) in stents, implanted in
      coronary arteries for >/= 3 months. In the PTCA group, angioplasty was performed
      at the discretion of the local investigator, and rotablation was performed by
      using a stepped-burr approach followed by adjunctive PTCA with low (</= 6 atm)
      inflation pressure. Intravascular ultrasound during the intervention and at
      follow-up was used in a substudy in 86 patients (45 PTCA, 41 ROTA). Angiography
      demonstrated no difference regarding the short-term outcome, with equivalent
      procedural success rates defined as remaining stenosis <30% (89% PTCA, 88% ROTA).
      However, the results showed that, in the long term, PTCA was a significantly
      better strategy than ROTA. Mean net gain in minimal lumen diameter was 0.67 mm
      and 0.45 mm for PTCA and ROTA, respectively (P=0.0019). Mean gain in diameter
      stenosis was 25% and 17% (P=0.002), resulting in restenosis (>/= 50%) rates of
      51% (PTCA) and 65% (ROTA) (P=0.039). By intravascular ultrasound, the major
      difference was the missing stent over-expansion during PTCA after ROTA. Six-month
      event-free survival was significantly higher after PTCA (91.3%) compared with
      ROTA (79.6%, P=0.0052). CONCLUSIONS: In terms of the primary objective of the
      study, PTCA produced a significantly better long-term outcome than ROTA followed
      by adjunctive low-pressure PTCA.

PMID- 11827924
TI  - Quality of life in the antiarrhythmics versus implantable defibrillators trial:
      impact of therapy and influence of adverse symptoms and defibrillator shocks.
AB  - BACKGROUND: Implantable cardioverter defibrillator (ICD) use reduces mortality in
      patients with serious ventricular arrhythmias compared with antiarrhythmic drug
      (AAD) use. However, the relative impact of these therapies on self-perceived
      quality of life (QoL) is unknown. METHODS AND RESULTS: Three self-administered
      instruments were used to measure generic and disease-specific QoL in
      Antiarrhythmics Versus Implantable Defibrillators trial participants. Generalized
      linear models were used to assess the relationships between self-perceived QoL
      and treatment (AAD versus ICD) and adverse symptoms and ICD shocks. To minimize
      the impact of missing data, only patients surviving 1 year were included in the
      primary analyses. Baseline characteristics among QoL participants (n=905) and
      nonparticipants (n=111) were similar, but participants who survived 1 year
      (n=800) were healthier at baseline than nonsurvivors (n=105). Of the 800 patients
      in the primary analysis, characteristics of those randomized to AAD (n=384)
      versus ICD (n=416) were similar. Overall, ICD and AAD use were associated with
      similar alterations in QoL. The development of sporadic shocks and adverse
      symptoms were each associated with reduced physical functioning and mental well
      being and increased concerns among ICD recipients, whereas development of adverse
      symptoms was associated with reduced physical functioning and increased concerns
      among AAD recipients. CONCLUSIONS: ICD and AAD therapy are associated with
      similar alterations in self-perceived QoL over 1-year follow-up. Adverse symptoms
      were associated with reduced self-perceived QoL in both groups, and sporadic
      shocks were associated with reduced QoL in ICD recipients.

PMID- 11827925
TI  - Utility of B-natriuretic peptide in detecting diastolic dysfunction: comparison
      with Doppler velocity recordings.
AB  - BACKGROUND: Although Doppler echocardiography has been used to identify abnormal
      left ventricular (LV) diastolic filling dynamics, inherent limitations suggest
      the need for additional measures of diastolic dysfunction. Because data suggest
      that B-natriuretic peptide (BNP) partially reflects ventricular pressure, we
      hypothesized that BNP levels could predict diastolic abnormalities in patients
      with normal systolic function. METHODS AND RESULTS: We studied 294 patients
      referred for echocardiography to evaluate ventricular function. Patients with
      abnormal systolic function were excluded. Cardiologists making the assessment of
      LV function were blinded to BNP levels. Patients were classified as normal,
      impaired relaxation, pseudonormal, and restrictivelike filling patterns. Patients
      diagnosed with evidence of abnormal LV diastolic function (n=119) had a mean BNP
      concentration of 286 +/- 31 pg/mL; those in the normal LV group (n=175) had a
      mean BNP concentration of 33 +/- 3 pg/mL. Patients with restrictive like filling
      patterns on echocardiography had the highest BNP levels (408 +/- 66 pg/mL), and
      patients with symptoms had higher BNP levels in all diastolic filling patterns.
      The area under the receiver-operating characteristic curve for BNP to detect any
      diastolic dysfunction was 0.92 (95% CI, 0.87 to 0.95; P<0.001). A BNP value of 62
      pg/mL had a sensitivity of 85%, a specificity of 83%, and an accuracy of 84% for
      detecting diastolic dysfunction. CONCLUSIONS: A rapid assay for BNP can reliably
      detect the presence of diastolic abnormalities on echocardiography. In patients
      with normal systolic function, elevated BNP levels and diastolic filling
      abnormalities might help to reinforce the diagnosis diastolic dysfunction.

PMID- 11827926
TI  - Gene therapy strategy for long-term myocardial protection using adeno-associated
      virus-mediated delivery of heme oxygenase gene.
AB  - BACKGROUND: Ischemia and oxidative stress are the leading mechanisms for tissue
      injury. An ideal strategy for preventive/protective therapy would be to develop
      an approach that could confer long-term transgene expression and, consequently,
      tissue protection from repeated ischemia/reperfusion injury with a single
      administration of a therapeutic gene. In the present study, we used recombinant
      adeno-associated virus (rAAV) as a vector for direct delivery of the
      cytoprotective gene heme oxygenase-1 (HO-1) into the rat myocardium, with the
      purpose of evaluating this strategy as a therapeutic approach for long-term
      protection from ischemia-induced myocardial injury. METHODS AND RESULTS: Human HO
      1 gene (hHO-1) was delivered to normal rat hearts by intramyocardial injection.
      AAV-mediated transfer of the hHO-1 gene 8 weeks before acute coronary artery
      ligation and release led to a dramatic reduction (>75%) in left ventricular
      myocardial infarction. The reduction in infarct size was accompanied by decreases
      in myocardial lipid peroxidation and in proapoptotic Bax and proinflammatory
      interleukin-1beta protein abundance, concomitant with an increase in
      antiapoptotic Bcl-2 protein level. This suggested that the transgene exerts its
      cardioprotective effects in part by reducing oxidative stress and associated
      inflammation and apoptotic cell death. CONCLUSIONS: This study documents the
      beneficial therapeutic effect of rAAV-mediated transfer, before myocardial
      injury, of a cytoprotective gene that confers long-term myocardial protection
      from ischemia/reperfusion injury. Our data suggest that this novel "pre-event"
      gene transfer approach may provide sustained tissue protection from future
      repeated episodes of injury and may be beneficial as preventive therapy for
      patients with or at risk of developing coronary ischemic events.

PMID- 11827927
TI  - Platelet-derived growth factor-AB limits the extent of myocardial infarction in a
      rat model: feasibility of restoring impaired angiogenic capacity in the aging
      heart.
AB  - BACKGROUND: Compared with younger patients, myocardial infarction in the elderly
      has been associated with less favorable clinical outcomes, which may be
      attributable to a decline in angiogenic capacity in the aging heart. METHODS AND
      RESULTS: To test the hypothesis that the functional phenotype of cardiac
      microvascular endothelial cells is maintained partly by a cardiac myocyte
      platelet-derived growth factor (PDGF)-B-induced paracrine pathway, we conducted
      in vitro studies with murine cardiac cells. These studies demonstrated that
      unlike young endothelial cells, endothelial cells of the aging heart do not
      express PDGF-B when cultured in the presence of cardiac myocytes. The functional
      significance of this endothelial dysregulation was assessed with an ex vivo
      pinnal cardiac allograft model to demonstrate that senescent cardiac angiogenic
      activity was depressed (2 of 17 allografts were viable in 18-month-old mice
      versus 19 of 20 in 3-month-old mice; P<0.01). PDGF-AB pretreatment specifically
      restored the viability of the cardiac allografts in the aging hosts (13 of 13
      allografts were viable; P<0.01 versus 18-month-old controls). Finally, in vivo
      studies in rat hearts demonstrated that pretreatment by intramyocardial delivery
      of PDGF-AB promotes angiogenesis and minimizes the extent of myocardial
      infarction in the aging hearts after coronary ligation (myocardial infarction
      size: 10.0 +/- 7.0% of left ventricular area in PDGF pretreatment [n=7] versus
      17.6 +/- 5.6% in control [n=5] groups; P<0.03). CONCLUSION: Aging hearts have
      impaired angiogenic function as a result of depressed PDGF-B production.
      Restoration of the dysregulated endothelial PDGF-mediated angiogenic pathway in
      the aging heart reverses the senescent impairment in cardioprotective angiogenic
      function and offers a foundation for developing novel therapies for
      cardiovascular disease in older individuals.

PMID- 11827928
TI  - Accelerated cardiomyopathy in mice with overexpression of cardiac G(s)alpha and a
      missense mutation in the alpha-myosin heavy chain.
AB  - BACKGROUND: To understand further the pathogenesis of familial hypertrophic
      cardiomyopathy, we determined how the cardiomyopathy induced by an Arg403-->Gln
      missense mutation in the alpha-myosin heavy chain (403) is affected by
      chronically enhancing sympathetic drive by mating the mice with those
      overexpressing G(s)alpha (G(s)alpha x403). METHODS AND RESULTS: Heart rate in 3
      month-old conscious mice was elevated similarly (P<0.05) in mice overexpressing
      G(s)alpha (G(s)alpha mice; 746 +/- 14 bpm) and G(s)alpha x403 mice (718+/- 19
      bpm) compared with littermate wild-type mice (WT; 623+/- 18 bpm) and 403 mice
      (594+/- 16 bpm). Left ventricular ejection fraction (LVEF), as determined by
      echocardiography, was enhanced in G(s)alpha x403 mice (88+/- 1%, P<0.001)
      compared with WT (69+/- 1%), 403 (75+/- 1%), and G(s)alpha (69 +/- 2%) mice.
      Isolated cardiomyocytes from G(s)alpha x403 mice also exhibited higher (P<0.001)
      baseline percent contraction (11.9+/- 0.5%) than WT (7.0+/- 0.5%), 403 (5.5+/-
      0.5%), and G(s)alpha (7.8+/- 0.3%) cardiomyocytes. Relaxation of myocytes was
      impaired in 403 mice compared with WT but enhanced in G(s)alpha and normalized in
      G(s)alpha x403 mice. This was also observed in vivo. In vivo isoproterenol (0.1
      microgram . kg(-1) . min(-1)) increased LVEF to maximal levels in G(s)alpha x403
      and G(s)alpha, whereas in 403, the response was attenuated compared with WT. At
      10 months of age, G(s)alpha x403 had significantly depressed LVEF (57 +/- 4%).
      Histopathological examination demonstrated that myocyte hypertrophy and fibrosis
      were already present in young G(s)alpha x403 mice and that old animals had severe
      cardiomyopathy. By 15 months of age, the survival of G(s)alpha x403 was 0%
      compared with 100% for WT, 71% for G(s)alpha, and 100% for 403 mice (P<0.05).
      CONCLUSIONS: These results show that the cardiomyopathy developed by G(s)alpha
      x403 mice is synergistic rather than additive, most likely owing to the elevated
      baseline function combined with enhanced responsiveness to sympathetic
      stimulation.

PMID- 11827929
TI  - Dynamic changes in three-dimensional architecture and vascular volume of
      transmural coronary microvasculature between diastolic- and systolic-arrested rat
      hearts.
AB  - BACKGROUND: The phase difference of coronary arterial and venous flows indicates
      the importance of intramyocardial capacitance vessels in storing diastolic flow
      and in discharging volume in systole. However, the anatomic and functional
      characteristics of the capacitance vessels are unclear. We aimed to clarify those
      characteristics with their transmural difference by 3D visualization of
      transmural microvessels under diastole and systole. METHODS AND RESULTS: We
      performed complete intracoronary filling of a contrast medium into Langendorff's
      Wistar rat hearts under (1) St Thomas-perfused diastolic arrest (D-mode) and (2)
      BaCl(2)-induced systolic arrest (S-mode). Precise transmural 3D architectures of
      capillaries and of pre- and post-capillary microvessels (ie, microvessels larger
      than capillaries) were visualized clearly with a confocal laser scanning
      microscope and x-ray microcomputed tomography (microCT), respectively. Vascular
      volume fraction (VF) and systolic-induced VF reduction rate from D- to S-mode
      were analyzed. The net capillary VF in D-mode (20.4 +/- 0.9%) was 10 times that
      of larger microvessels and was reduced in S-mode by 32% without capillary
      collapse. Systolic-induced VF reduction rate was smaller in capillaries than in
      larger microvessels (48%; P<0.05). The larger microvessel VF in D-mode (2.2 +/
      0.2%) was reduced in S-mode, accompanied by complicated 3D deformation.
      CONCLUSIONS: Capillaries were relatively resistant to the systolic extravascular
      compression compared with pre- and post-capillary microvessels, conveniently
      beneficial for the myocardial oxygen delivery throughout a cardiac cycle.
      Nevertheless, a larger change in the absolute volume of capillaries may function
      as effective capacitance. On one hand, the pre- and post-capillary microvessels
      showed a larger phasic change in resistance, which may function to maintain the
      capillary patency during systole.

PMID- 11827930
TI  - Induction of functional bradykinin b(1)-receptors in normotensive rats and mice
      under chronic Angiotensin-converting enzyme inhibitor treatment.
AB  - BACKGROUND: The physiological effects of ACE inhibitors may act in part through a
      kinin-dependent mechanism. We investigated the effect of chronic ACE-inhibitor
      treatment on functional kinin B(1)- and B(2)-receptor expression, which are the
      molecular entities responsible for the biological effects of kinins. METHODS AND
      RESULTS: Rats were subjected to different 6-week treatments using various
      mixtures of the following agents: ACE inhibitor, angiotensin AT(1)-receptor
      antagonist, and B(1)- and B(2)-receptor antagonists. Chronic ACE inhibition
      induced both renal and vascular B(1)-receptor expression, whereas B(2)-receptor
      expression was not modified. Furthermore, with B(1)-receptor antagonists, it was
      shown that B(1)-receptor induction was involved in the hypotensive effect of ACE
      inhibition. Using microdissection, we prepared 10 different nephron segments and
      found ACE-inhibitor-induced expression of functional B(1)-receptors in all
      segments. ACE-inhibitor-induced B(1)-receptor induction involved homologous
      upregulation, because it was prevented by B(1)-receptor antagonist treatment.
      Finally, using B(2)-receptor knockout mice, we showed that ACE-inhibitor-induced
      B(1)-receptor expression was B(2)-receptor independent. CONCLUSIONS: This study
      provides the first evidence that chronic ACE-inhibitor administration is
      associated with functional vascular and renal B(1)-receptor induction, which is
      involved in ACE-inhibitor-induced hypotension. The observed B(1)-receptor
      induction in the kidney might participate in the known renoprotective effects of
      ACE inhibition.

PMID- 11827931
TI  - Activation of nuclear factor-kappa B significantly contributes to lumen loss in a
      rabbit iliac artery balloon angioplasty model.
AB  - BACKGROUND: To investigate the contribution of inflammation to postangioplasty
      lumen loss, we used an adenoviral gene therapy approach to inhibit the central
      inflammatory mediator nuclear factor-kappaB (NF-kappaB) by overexpression of its
      natural inhibitor, IkappaBalpha. METHODS AND RESULTS: The adenovirus carrying
      human IkappaBalpha was applied immediately after balloon dilatation by a double
      balloon catheter in a rabbit iliac artery restenosis model. Immunohistochemistry
      of IkappaBalpha revealed that mainly smooth muscle cells of the media but also
      cells of the adventitia were transduced and expressed the transgene IkappaB alpha
      for >/= 8 days. At this time point, intercellular adhesion molecule-1 (30%) and
      monocyte chemotactic protein-1 (50%) expression, as well as recruitment of
      macrophages into the wounded area (90%), were significantly reduced in IkappaB
      alpha-treated vessels. In addition, expression of inhibitor of apoptosis proteins
      was reduced and the percentage of apoptotic cells was increased compared with
      control-treated contralateral vessels. Animals killed 5 weeks after treatment
      exhibited a significantly reduced degree of lumen narrowing (P<0.02) on the side
      treated with adenovirus IkappaBalpha. The lumen gain of approximately 40% was due
      to positive remodeling. CONCLUSIONS: From these data, we conclude that balloon
      angioplasty-induced activation of NF-kappaB contributes to lumen loss likely via
      induction of an inflammatory response and a decrease in the rate of apoptosis.
      These data show for the first time that inflammation mediated by NF-kappaB is
      involved in postangioplasty lumen narrowing. Specific and more potent inhibitors
      of NF-kappaB might therefore be a useful therapeutic measure to improve clinical
      outcome after balloon dilatation.

PMID- 11827932
TI  - Differential actions of vasopeptidase inhibition versus angiotensin-converting
      enzyme inhibition on diuretic therapy in experimental congestive heart failure.
AB  - BACKGROUND: Omapatrilat (OMA), a vasopeptidase inhibitor, simultaneously inhibits
      angiotensin-converting enzyme (ACE) and neutral endopeptidase, which degrades
      vasodilatory factors (eg, ADM) and natriuretic peptides. Based on the beneficial
      cardiorenal and humoral properties of the natriuretic peptides, we hypothesized
      that an acute vasopeptidase inhibitor with or without diuretic would result in
      more favorable cardiorenal and hormonal actions than ACE inhibition plus diuretic
      (ACEI+D) in congestive heart failure. METHODS AND RESULTS: We compared the
      actions of OMA alone and with diuretic (OMA+D) to ACEI+D in a model of pacing
      induced congestive heart failure. OMA+D decreased pulmonary arterial and
      pulmonary capillary wedge pressures to a greater level than OMA alone or ACEI+D.
      Glomerular filtration rate was lower with ACEI+D than with either OMA group.
      Plasma renin activity and aldosterone immediately increased with ACEI+D, whereas
      OMA+D resulted in higher plasma renin activity and a delayed increase in
      aldosterone. OMA alone did not increase plasma renin activity and aldosterone,
      but resulted in a sustained increase in plasma adrenomedullin, with higher
      urinary atrial natriuretic peptide, adrenomedullin, and cGMP excretions than with
      ACEI+D. CONCLUSIONS: Acute administration of OMA with or without diuretic results
      in more favorable cardiorenal and humoral responses in experimental congestive
      heart failure than does ACEI+D. There is no acute activation of renin and
      aldosterone with OMA alone such as occurs with ACEI+D and OMA+D. Thus, OMA with
      or without a diuretic possesses beneficial cardiorenal and humoral actions
      comparable to those observed with ACEI+D that can be explained by potentiation of
      natriuretic peptides.

PMID- 11827933
TI  - Importance of continuous chest compressions during cardiopulmonary resuscitation:
      improved outcome during a simulated single lay-rescuer scenario.
AB  - BACKGROUND: Interruptions to chest compression-generated blood flow during
      cardiopulmonary resuscitation (CPR) are detrimental. Data show that such
      interruptions for mouth-to-mouth ventilation require a period of "rebuilding" of
      coronary perfusion pressure to obtain the level achieved before the interruption.
      Whether such hemodynamic compromise from pausing to ventilate is enough to affect
      outcome is unknown. METHODS AND RESULTS: Thirty swine (weight 35 +/- 2 kg)
      underwent 3 minutes of untreated ventricular fibrillation before 12 minutes of
      basic life support CPR. Animals were randomized to receive either standard airway
      (A), breathing (B), and compression (C) CPR with expired-gas ventilation in a
      15:2 compression-to-ventilation ratio or continuous chest compression CPR. Those
      randomized to the standard 15:2 group had no chest compressions for a period of
      16 seconds each time the 2 ventilations were delivered. Defibrillation was
      attempted at 15 minutes of cardiac arrest. All resuscitated animals were
      supported in an intensive care environment for 1 hour, then in a maintenance
      facility for 24 hours. The primary end point of neurologically normal 24-hour
      survival was significantly better in the experimental group receiving continuous
      chest compression CPR (12 of 15 versus 2 of 15; P<0.0001). CONCLUSIONS: Mouth-to
      mouth ventilation performed by single layperson rescuers produces substantial
      interruptions in chest compression-supported circulation. Continuous chest
      compression CPR produces greater neurologically normal 24-hour survival than
      standard ABC CPR when performed in a clinically realistic fashion. Any technique
      that minimizes lengthy interruptions of chest compressions during the first 10 to
      15 minutes of basic life support should be given serious consideration in future
      efforts to improve outcome results from cardiac arrest.

PMID- 11827934
TI  - Monocyte/macrophage regulation of vascular calcification in vitro.
AB  - BACKGROUND: Calcification is a common complication of atherosclerosis and other
      chronic inflammatory processes that involves infiltration of monocytes and
      accumulation of macrophages. METHODS AND RESULTS: To determine whether these
      cells modulate vascular calcification in vitro, calcifying vascular cells (CVCs),
      a subpopulation of osteoblast-like cells derived from the artery wall, were
      cocultured with human peripheral blood monocytes for 5 days. Results showed that
      alkaline phosphatase (ALP) activity, a marker of osteoblastic differentiation,
      was significantly greater in cocultures than in cultures of CVCs or monocytes
      alone. Both ALP activity and matrix mineralization increased in proportion to the
      number of monocytes added. Activation of monocyte/macrophages (M/Ms) by oxidized
      LDL further increased ALP activity in cocultures. However, neither conditioned
      medium from oxidized-LDL-activated M/Ms or transwell coculture had this effect on
      CVCs, which suggests a need for cell-to-cell contact. In contrast, conditioned
      medium from lipopolysaccharide-activated M/Ms increased ALP activity of CVCs.
      ELISA showed that lipopolysaccharide-activated M/Ms secreted tumor necrosis
      factor-alpha, and neutralizing antibody to tumor necrosis factor-alpha attenuated
      the induction of ALP activity by the conditioned media. CONCLUSIONS: These
      results suggest that M/Ms enhance in vitro vascular calcification via 2
      independent mechanisms: cell-cell interaction and production of soluble factors
      such as tumor necrosis factor-alpha.

PMID- 11827935
TI  - No-reflow phenomenon.

PMID- 11827936
TI  - Three-dimensional computed tomography showing partial anomalous pulmonary venous
      connection complicated by the scimitar syndrome.

PMID- 11827937
TI  - 3D-magnetic resonance angiogram of heterotopic heart transplant.

PMID- 11827939
TI  - Weight loss decreases C-reactive protein levels.

PMID- 11827940
TI  - Pixelating the brain.

PMID- 11827941
TI  - Why names.

PMID- 11827942
TI  - Positional candidate cloning of a QTL in dairy cattle: identification of a
      missense mutation in the bovine DGAT1 gene with major effect on milk yield and
      composition.
AB  - We recently mapped a quantitative trait locus (QTL) with a major effect on milk
      composition--particularly fat content--to the centromeric end of bovine
      chromosome 14. We subsequently exploited linkage disequilibrium to refine the map
      position of this QTL to a 3-cM chromosome interval bounded by microsatellite
      markers BULGE13 and BULGE09. We herein report the positional candidate cloning of
      this QTL, involving (1) the construction of a BAC contig spanning the
      corresponding marker interval, (2) the demonstration that a very strong candidate
      gene, acylCoA:diacylglycerol acyltransferase (DGAT1), maps to that contig, and
      (3) the identification of a nonconservative K232A substitution in the DGAT1 gene
      with a major effect on milk fat content and other milk characteristics.

PMID- 11827943
TI  - Combining mouse congenic strains and microarray gene expression analyses to study
      a complex trait: the NOD model of type 1 diabetes.
AB  - Combining congenic mapping with microarray expression profiling offers an
      opportunity to establish functional links between genotype and phenotype for
      complex traits such as type 1 diabetes (T1D). We used high-density
      oligonucleotide arrays to measure the relative expression levels of >39,000 genes
      and ESTs in the NOD mouse (a murine model of T1D and other autoimmune
      conditions), four NOD-derived diabetes-resistant congenic strains, and two
      nondiabetic control strains. We developed a simple, yet general, method for
      measuring differential expression that provides an objective assessment of
      significance and used it to identify >400 gene expression differences and eight
      new candidates for the Idd9.1 locus. We also discovered a potential early
      biomarker for autoimmune hemolytic anemia that is based on different levels of
      erythrocyte-specific transcripts in the spleen. Overall, however, our results
      suggest that the dramatic disease protection conferred by six Idd loci (Idd3,
      Idd5.1, Idd5.2, Idd9.1, Idd9.2, and Idd9.3) cannot be rationalized in terms of
      global effects on the noninduced immune system. They also illustrate the degree
      to which regulatory systems appear to be robust to genetic variation. These
      observations have important implications for the design of future microarray
      based studies in T1D and, more generally, for studies that aim to combine genome
      wide expression profiling and congenic mapping.

PMID- 11827944
TI  - High-throughput imaging of brain gene expression.
AB  - Voxelation is a new method for acquisition of three dimensional (3D) gene
      expression patterns in the brain. It employs high-throughput analysis of
      spatially registered voxels (cubes) to produce multiple volumetric maps of gene
      expression analogous to the images reconstructed in biomedical imaging systems.
      Using microarrays, 24 voxel images of coronal hemisections at the level of the
      hippocampus of both the normal human brain and Alzheimer's disease brain were
      acquired for 2000 genes. The analysis revealed a common network of coregulated
      genes, and allowed identification of putative control regions. In addition,
      singular value decomposition (SVD), a mathematical method used to provide
      economical explanations of complex data sets, produced images that distinguished
      between brain structures, including cortex, caudate, and hippocampus. The results
      suggest that voxelation will be a useful approach for understanding how the
      genome constructs the brain.

PMID- 11827945
TI  - Metallochaperones and metal-transporting ATPases: a comparative analysis of
      sequences and structures.
AB  - A comparative structural genomic analysis of a new class of metal-trafficking
      proteins can provide insights into the intracellular chemistry of reactive
      cofactors such as copper and zinc. Starting from the sequences of the
      metallochaperone Atx1 and from the first soluble domain of the copper
      transporting ATPase Ccc2, both from yeast, a search on the available genomes was
      performed using a homology criterion and a metal-binding motif x'-x"-C-x'''-x''''
      C. By limiting ourselves to 20% identity with any of the proteins found, several
      soluble copper-transport proteins were identified, as well as soluble domains of
      membrane-bound ATPases. Structural models were calculated using high-resolution
      solution structures as templates, and the models were validated using statistical
      and energy criteria. Residue conservation and substitution have been interpreted
      and discussed in terms of structure-function relationship. The potential energy
      surfaces have been analyzed in terms of protein-protein interactions. We find
      that metallochaperones and their physiological partner ATPases from several
      phylogenetic kingdoms recognize one another, via an interplay of electrostatics,
      hydrogen bonding, and hydrophobic interactions, in a manner that precisely
      orients the metal-binding side chains for rapid metal transfer between otherwise
      tight binding sites. Finally, other putative metal-transport proteins are
      mentioned that have low homology and/or a different metal-binding consensus motif
      and that appear to use similar structures for recognition and transfer. This
      analysis highlights the wealth and the complexity of the field.

PMID- 11827946
TI  - Molecular fossils in the human genome: identification and analysis of the
      pseudogenes in chromosomes 21 and 22.
AB  - We have developed an initial approach for annotating and surveying pseudogenes in
      the human genome. We search human genomic DNA for regions that are similar to
      known protein sequences and contain obvious disablements (i.e., mid-sequence stop
      codons or frameshifts), while ensuring minimal overlap with annotations of known
      genes. Pseudogenes can be divided into "processed" and "nonprocessed"; the former
      are reverse transcribed from mRNA (and therefore have no intron structure),
      whereas the latter presumably arise from genomic duplications. We annotate
      putative processed pseudogenes based on whether there is a continuous span of
      homology that is >70% of the length of the closest matching human protein (i.e.,
      with introns removed), or whether there is evidence of polyadenylation. We have
      applied our approach to chromosomes 21 and 22, the first parts of the human
      genome completely sequenced, finding 190 new pseudogene annotations beyond the
      264 reported by the sequencing centers. In total, on chromosomes 21 and 22, there
      are 189 processed pseudogenes, 195 nonprocessed pseudogenes, and, additionally,
      70 pseudogenic immunoglobulin gene segments. (Detailed assignments are available
      at http://bioinfo.mbb.yale.edu/genome/pseudogene or
      http://genecensus.org/pseudogene.) By extrapolation, we predict that there could
      be up to approximately 20,000 pseudogenes in the whole human genome, with a
      little more than half of them processed. We have determined the main populations
      and clusters of pseudogenes on chromosomes 21 and 22. There are notable excesses
      of pseudogenes relative to genes near the centromeres of both chromosomes,
      indicating the existence of pseudogenic "hot-spots" in the genome. We have looked
      at the distribution of InterPro families and Gene Ontology (GO) functional
      categories in our pseudogenes. Overall, the families in both processed and
      nonprocessed pseudogene populations occur according to a similar power-law
      distribution as that found for the occurrence of gene families, with a few big
      families and many small ones. The processed population is, in particular,
      enriched in highly expressed ribosomal-protein sequences (approximately 20%),
      which appear fairly evenly distributed across the chromosomes. We compared
      processed pseudogenes of different evolutionary ages, observing a high degree of
      similarity between "ancient" and "modern" subpopulations. This may be
      attributable to the consistently high expression of ribosomal proteins over
      evolutionary time. Finally, we find that chromosome 22 pseudogene population is
      dominated by immunoglobulin segments, which have a greater rate of disablement
      per amino acid than the other pseudogene populations and are also substantially
      more diverged.

PMID- 11827948
TI  - Control genes and variability: absence of ubiquitous reference transcripts in
      diverse mammalian expression studies.
AB  - Control genes, commonly defined as genes that are ubiquitously expressed at
      stable levels in different biological contexts, have been used to standardize
      quantitative expression studies for more than 25 yr. We analyzed a group of large
      mammalian microarray datasets including the NCI60 cancer cell line panel, a
      leukemia tumor panel, and a phorbol ester induction time course as well as human
      and mouse tissue panels. Twelve housekeeping genes commonly used as controls in
      classical expression studies (including GAPD, ACTB, B2M, TUBA, G6PD, LDHA, and
      HPRT) show considerable variability of expression both within and across
      microarray datasets. Although we can identify genes with lower variability within
      individual datasets by heuristic filtering, such genes invariably show different
      expression levels when compared across other microarray datasets. We confirm
      these results with an analysis of variance in a controlled mouse dataset, showing
      the extent of variability in gene expression across tissues. The results show the
      problems inherent in the classical use of control genes in estimating gene
      expression levels in different mammalian cell contexts, and highlight the
      importance of controlled study design in the construction of microarray
      experiments.

PMID- 11827947
TI  - In vivo regulation of human skeletal muscle gene expression by thyroid hormone.
AB  - Thyroid hormones are key regulators of metabolism that modulate transcription via
      nuclear receptors. Hyperthyroidism is associated with increased metabolic rate,
      protein breakdown, and weight loss. Although the molecular actions of thyroid
      hormones have been studied thoroughly, their pleiotropic effects are mediated by
      complex changes in expression of an unknown number of target genes. Here, we
      measured patterns of skeletal muscle gene expression in five healthy men treated
      for 14 days with 75 microg of triiodothyronine, using 24,000 cDNA element
      microarrays. To analyze the data, we used a new statistical method that
      identifies significant changes in expression and estimates the false discovery
      rate. The 381 up-regulated genes were involved in a wide range of cellular
      functions including transcriptional control, mRNA maturation, protein turnover,
      signal transduction, cellular trafficking, and energy metabolism. Only two genes
      were down-regulated. Most of the genes are novel targets of thyroid hormone.
      Cluster analysis of triiodothyronine-regulated gene expression among 19 different
      human tissues or cell lines revealed sets of coregulated genes that serve similar
      biologic functions. These results define molecular signatures that help to
      understand the physiology and pathophysiology of thyroid hormone action.

PMID- 11827949
TI  - The evolution of DNA regulatory regions for proteo-gamma bacteria by interspecies
      comparisons.
AB  - The comparison of homologous noncoding DNA for organisms a suitable evolutionary
      distance apart is a powerful tool for the identification of cis regulatory
      elements for transcription and translation and for the study of how they assemble
      into functional modules. We have fit the three parameters of an affine global
      probabilistic alignment algorithm to establish the background mutation rate of
      noncoding sequence between E. coli and a series of gamma proteobacteria ranging
      from Salmonella to Vibrio. The lower bound we find to the neutral mutation rate
      is sufficiently high, even for Salmonella, that most of the conservation of
      noncoding sequence is indicative of selective pressures rather than of
      insufficient time to evolve. We then use a local version of the alignment
      algorithm combined with our inferred background mutation rate to assign a
      significance to the degree of local sequence conservation between orthologous
      genes, and thereby deduce a probability profile for the upstream regulatory
      region of all E. coli protein-coding genes. We recover 75%-85% (depending on
      significance level) of all regulatory sites from a standard compilation for E.
      coli, and 66%-85% of sigma sites. We also trace the evolution of known regulatory
      sites and the groups associated with a given transcription factor. Furthermore,
      we find that approximately one-third of paralogous gene pairs in E. coli have a
      significant degree of correlation in their regulatory sequence. Finally, we
      demonstrate an inverse correlation between the rate of evolution of transcription
      factors and the number of genes they regulate. Our predictions are available at
      http://www.physics.rockefeller.edu/([tilde-see text])siggia.

PMID- 11827950
TI  - Estimating coarse gene network structure from large-scale gene perturbation data.
AB  - Large scale gene perturbation experiments generate information about the number
      of genes whose activity is directly or indirectly affected by a gene
      perturbation. From this information, one can numerically estimate coarse
      structural network features such as the total number of direct regulatory
      interactions and the number of isolated subnetworks in a transcriptional
      regulation network. Applied to the results of a large-scale gene knockout
      experiment in the yeast Saccharomyces cerevisiae, the results suggest that the
      yeast transcriptional regulatory network is very sparse, containing no more
      direct regulatory interactions than genes. The network comprises >100 independent
      subnetworks.

PMID- 11827951
TI  - V-SINEs: a new superfamily of vertebrate SINEs that are widespread in vertebrate
      genomes and retain a strongly conserved segment within each repetitive unit.
AB  - We have identified a new superfamily of vertebrate short interspersed repetitive
      elements (SINEs), designated V-SINEs, that are widespread in fishes and frogs.
      Each V-SINE includes a central conserved domain preceded by a 5'-end tRNA-related
      region and followed by a potentially recombinogenic (TG)(n) tract, with a 3' tail
      derived from the 3' untranslated region (UTR) of the corresponding partner long
      interspersed repetitive element (LINE) that encodes a functional reverse
      transcriptase. The central domain is strongly conserved and is even found in
      SINEs in the lamprey genome, suggesting that V-SINEs might be approximately 550
      Myr old or older in view of the timing of divergence of the lamprey lineage from
      the bony fish lineage. The central conserved domain might have been subject to
      some form of positive selection. Although the contemporary 3' tails of V-SINEs
      differ from one another, it is possible that the original 3' tail might have been
      replaced, via recombination, by the 3' tails of more active partner LINEs,
      thereby retaining retropositional activity and the ability to survive for long
      periods on the evolutionary time scale. It seems plausible that V-SINEs may have
      some function(s) that have been maintained by the coevolution of SINEs and LINEs
      during the evolution of vertebrates.

PMID- 11827952
TI  - Fully automatic quantification of microarray image data.
AB  - DNA microarrays are now widely used to measure expression levels and DNA copy
      number in biological samples. Ratios of relative abundance of nucleic acids are
      derived from images of regular arrays of spots containing target genetic material
      to which fluorescently labeled samples are hybridized. Whereas there are a number
      of methods in use for the quantification of images, many of the software systems
      in wide use either encourage or require extensive human interaction at the level
      of individual spots on arrays. We present a fully automatic system for microarray
      image quantification. The system automatically locates both subarray grids and
      individual spots, requiring no user identification of any image coordinates.
      Ratios are computed based on explicit segmentation of each spot. On a typical
      image of 6000 spots, the entire process takes less than 20 sec. We present a
      quantitative assessment of performance on multiple replicates of genome-wide
      array-based comparative genomic hybridization experiments. By explicitly
      identifying the pixels in each spot, the system yields more accurate estimates of
      ratios than systems assuming spot circularity. The software, called, runs on
      Windows platforms and is available free of charge for academic use.

PMID- 11827953
TI  - ViewGene: a graphical tool for polymorphism visualization and characterization.
AB  - The human genome project is producing an enormous amount of sequence data, based
      on which single base changes between individuals can be identified.
      Unfortunately, computer tools that were adequate for sequence assembly are less
      than ideal for the characterization of polymorphism data [single nucleotide (snp)
      or insertion/deletion (indel)] and other sequence features, and their
      relationship to each other. We have developed viewGene as a flexible tool that
      takes input from a number of sequence formats and analysis programs (Genbank,
      FASTA, RepeatMasker, Cross match, BLAST, user-defined data) to construct a
      sequence reference scaffold that can be viewed through a simple graphical
      interface. polymorphisms generated from many sources can be added to this
      scaffold through the same sequence formats, with a variety of options to control
      what is displayed. Large amounts of polymorphism data can be organized so that
      patterns and haplotypes can be readily discerned. In our laboratory, viewGene has
      been used to view annotated genbank records, find nonrepetitive sequence
      fragments for polymorphism detection, and visualize similarity search results.
      Manipulation, cross-referencing, and haplotype viewing of snp data are essential
      for quality assessment and identification of variants associated with genetic
      disease, and viewGene provides all three of these important functions.

PMID- 11827954
TI  - A nomenclature system for the tree of human Y-chromosomal binary haplogroups.
AB  - The Y chromosome contains the largest nonrecombining block in the human genome.
      By virtue of its many polymorphisms, it is now the most informative haplotyping
      system, with applications in evolutionary studies, forensics, medical genetics,
      and genealogical reconstruction. However, the emergence of several unrelated and
      nonsystematic nomenclatures for Y-chromosomal binary haplogroups is an increasing
      source of confusion. To resolve this issue, 245 markers were genotyped in a
      globally representative set of samples, 74 of which were males from the Y
      Chromosome Consortium cell line repository. A single most parsimonious phylogeny
      was constructed for the 153 binary haplogroups observed. A simple set of rules
      was developed to unambiguously label the different clades nested within this
      tree. This hierarchical nomenclature system supersedes and unifies past
      nomenclatures and allows the inclusion of additional mutations and haplogroups
      yet to be discovered.

PMID- 11827955
TI  - In silico prediction of scaffold/matrix attachment regions in large genomic
      sequences.
AB  - Scaffold/matrix attachment regions (S/MARs) are essential regulatory DNA elements
      of eukaryotic cells. They are major determinants of locus control of gene
      expression and can shield gene expression from position effects. Experimental
      detection of S/MARs requires substantial effort and is not suitable for large
      scale screening of genomic sequences. In silico prediction of S/MARs can provide
      a crucial first selection step to reduce the number of candidates. We used
      experimentally defined S/MAR sequences as the training set and generated a
      library of new S/MAR-associated, AT-rich patterns described as weight matrices. A
      new tool called SMARTest was developed that identifies potential S/MARs by
      performing a density analysis based on the S/MAR matrix library
      (http://www.genomatix.de/cgi-bin/smartest_pd/smartest.pl). S/MAR predictions were
      evaluated by using six genomic sequences from animal and plant for which S/MARs
      and non-S/MARs were experimentally mapped. SMARTest reached a sensitivity of 38%
      and a specificity of 68%. In contrast to previous algorithms, the SMARTest
      approach does not depend on the sequence context and is suitable to analyze long
      genomic sequences up to the size of whole chromosomes. To demonstrate the
      feasibility of large-scale S/MAR prediction, we analyzed the recently published
      chromosome 22 sequence and found 1198 S/MAR candidates.

PMID- 11827956
TI  - Interaction of fibroblast growth factor receptor 3 and the adapter protein SH2-B.
      A role in STAT5 activation.
AB  - Fibroblast growth factor receptor 3 (FGFR3) influences a diverse array of
      biological processes, including cell growth, differentiation, and migration.
      Activating mutations in FGFR3 are associated with multiple myeloma, cervical
      carcinoma, and bladder cancer. To identify proteins that interact with FGFR3 and
      which may mediate FGFR3-dependent signaling, a yeast two-hybrid screen was
      employed using the cytoplasmic kinase domain of FGFR3 as bait. We identified the
      adapter protein SH2-B as an FGFR3-interacting protein. Coimmunoprecipitation
      experiments demonstrate binding of the SH2-B beta isoform to FGFR3 in 293T cells.
      Tyrosine phosphorylation of SH2-B beta was observed when coexpressed with
      activated FGFR3 mutants such as the weakly activated mutant N540K or the strongly
      activated mutant K650E, both associated with human developmental syndromes. The
      extent of tyrosine phosphorylation of SH2-B beta correlates with receptor
      activation, suggesting that FGFR3 activation mediates tyrosine phosphorylation of
      SH2-B beta. Furthermore, two tyrosine phosphorylation sites of FGFR3, Tyr-724 and
      Tyr-760, are required for optimal binding of the Src homology-2 (SH2) domain of
      SH2-B beta. We also demonstrate the phosphorylation and nuclear translocation of
      Stat5 by activated FGFR3, which increases in response to overexpression of SH2-B
      beta. Taken together, our results identify SH2-B beta as a novel FGFR3 binding
      partner that mediates signal transduction.

PMID- 11827957
TI  - Tumor suppressor p53 mediates apoptotic cell death triggered by cyclosporin A.
AB  - The tumor suppressor p53 can induce growth arrest and cell death via apoptosis in
      response to a number of cellular stresses. We have shown previously that the
      immunosuppressant cyclosporin A (CsA) induces programmed cell death with typical
      features of apoptosis in rat glioma cells. We report that CsA treatment results
      in increased level of the p53 tumor suppressor, its nuclear accumulation, and
      transcriptional activation of p53-dependent genes. The increase of p53 correlates
      with the elevation of p21(Waf1) and Bax protein expression. The increased level
      of Bax protein was accompanied with changes in its subcellular localization and
      association with mitochondria. Importantly, we demonstrate that glioma cells
      stably transfected with a mutant p53 (p53Val135) fail to increase p21 and Bax
      protein levels and are less sensitive to CsA-induced apoptosis. Furthermore,
      primary fibroblasts from p53-/- knockout mice are significantly more resistant to
      CsA-induced apoptosis compared with their corresponding counterparts containing
      functional p53. Together, our results suggest that the apoptotic program
      activated by CsA can be mediated by activation of p53 tumor suppressor and
      potentiation of its ability to initiate apoptosis.

PMID- 11827958
TI  - Distinct roles of mitogen-activated protein kinase pathways in GATA-4
      transcription factor-mediated regulation of B-type natriuretic peptide gene.
AB  - The expression of cardiac hormones, atrial natriuretic peptide and B-type
      natriuretic peptide, is induced by cardiac wall stretch and responds to various
      hypertrophic agonists such as endothelin-1. In cardiac myocytes, endothelin-1
      induces GATA-4 binding to the B-type natriuretic peptide gene, but the signaling
      pathways involved in endothelin-1-induced GATA-4 activation are unknown. Mitogen
      activated protein kinase pathways are stimulated in response to various
      extracellular stimuli, and they modulate the function of several transcription
      activators. Here we show that inhibition of p38 kinase with SB203580 inhibited
      endothelin-1-induced GATA-4 binding to B-type natriuretic peptide gene and serine
      phosphorylation of GATA-4. Inhibition of extracellular signal-regulated protein
      kinase with MEK1 inhibitor PD98059 reduced basal and p38-induced GATA-4 binding
      activity, but it had no significant effect on endothelin-1-induced GATA-4 binding
      activity. Overexpression of p38 kinase pathway, but not extracellular signal
      regulated kinase or c-Jun N-terminal protein kinase, activated GATA-4 binding to
      B-type natriuretic peptide gene and induced rat B-type natriuretic peptide
      promoter activity via proximal GATA binding sites. In conclusion, these findings
      demonstrate that activation of p38 kinase is necessary for hypertrophic agonist
      induced GATA-4 binding to B-type natriuretic peptide gene and sufficient for GATA
      dependent B-type natriuretic peptide gene expression.

PMID- 11827959
TI  - Capacitative calcium entry contributes to nuclear factor of activated T-cells
      nuclear translocation and hypertrophy in cardiomyocytes.
AB  - In nonexcitable cells, depletion of endoplasmic reticulum Ca(2+) stores leads to
      activation of plasma membrane Ca(2+) channels, a process termed capacitative
      Ca(2+) entry. Here, we demonstrate that this pathway functions in cells that also
      contain voltage-gated Ca(2+) channels, neonatal rat ventricular myocytes. The
      depletion of sarcoplasmic reticulum Ca(2+) stores elicited a prolonged increase
      in cytoplasmic Ca(2+) dependent on extracellular Ca(2+). Inhibitors of store
      operated channels but not L-type channels diminished this response. The
      importance of this pathway to cardiac hypertrophy, which often is dependent on
      Ca(2+)/calmodulin-dependent transcription factors, was also assessed in this
      model. Hypertrophy and atrial natriuretic factor expression induced by
      angiotensin II or phenylephrine was more effectively attenuated by inhibitors of
      capacitative entry than of L-type channels. Additionally, cardiomyocytes were
      transfected with a construct encoding a fluorescent nuclear factor of activated T
      cells chimeric protein to follow nuclear localization in response to
      thapsigargin, angiotensin II, and phenylephrine. This translocation was
      completely prevented by inhibitors of capacitative Ca(2+) entry and only
      partially abrogated by inhibitors of L-type channels. In contrast, a hypertrophic
      response induced by overexpression of the transcription factor MEK1 was
      unaffected by inhibitors of capacitative entry. Together, these data suggest a
      role for CCE in cardiomyocyte physiology and, in particular, in Ca(2+)-mediated
      cardiac hypertrophy.

PMID- 11827960
TI  - Inhibition of Ca2+/calmodulin-dependent protein kinase blocks morphological
      differentiation of plasmodium gallinaceum zygotes to ookinetes.
AB  - Once ingested by mosquitoes, malaria parasites undergo complex cellular changes.
      These include zygote formation, transformation of zygote to ookinete, and
      differentiation from ookinete to oocyst. Within the oocyst, the parasite
      multiplies into numerous sporozoites. Modulators of intracellular calcium
      homeostasis, MAPTAM, and TMB-8 blocked ookinete development as did the calmodulin
      (CaM) antagonists W-7 and calmidazolium. Ca(2+)/CaM-dependent protein kinase
      inhibitor KN-93 also blocked zygote elongation, while its ineffective analog KN
      92 did not have such effect. In vitro both zygote and ookinete extracts
      efficiently phosphorylated autocamtide-2, a classic CaM kinase substrate, which
      could be blocked by calmodulin antagonists W-7 and calmidazolium and CaM kinase
      inhibitor KN-93. These results demonstrated the presence of calmodulin-dependent
      CaM kinase activity in the parasite. KN-93-treated parasites, however, expressed
      the ookinete-specific enzyme chitinase and the ookinete surface antigen Pgs28
      normally, suggesting that the morphologically untransformed parasites are
      biochemically mature ookinetes. In mosquitoes, KN-93-treated parasites did not
      develop as oocysts, while KN-92-treated parasites produced similar numbers of
      oocysts as controls. These data suggested that in Plasmodium gallinaceum
      morphological development of zygote to ookinete, but not its biochemical
      maturation, relies on Ca(2+)/CaM-dependent protein kinase activity and
      demonstrated that the morphological differentiation is essential for the further
      development of the parasite in infected blood-fed mosquitoes.

PMID- 11827961
TI  - Site-specific photo-cross-linking between lambda integrase and its DNA
      recombination target.
AB  - The site-specific recombinase (Int) of bacteriophage lambda is a heterobivalent
      DNA-binding protein and is composed of three domains as follows: an amino
      terminal domain that binds with high affinity to "arm-type" sequences within the
      recombination target DNA (att sites), a carboxyl-terminal domain that contains
      all of the catalytic functions, and a central domain that contributes
      significantly to DNA binding at the "core-type" sequences where DNA cleavage and
      ligation are executed. We constructed a family of core-type DNA oligonucleotides,
      each of which contained the photoreactive analog 4-thiodeoxythymidine (4-thioT)
      at a different position. When tested for their respective abilities to promote
      covalent cross-links with Int after irradiation with UV light at 366 nm, one
      oligonucleotide stood out dramatically. The 4-thioT substitution on the DNA
      strand opposite the site of Int cleavage led to photo-induced cross-linking
      efficiencies of approximately 20%. The efficiency and specificity of Int binding
      and cleavage at this 4-thioT-substituted core site was shown to be largely
      uncompromised, and its ability to participate in a full site-specific
      recombination reaction was reduced only slightly. Identification of the photo
      cross-linked residue as Lys-141 in the central domain provides, along with other
      results, several insights about the nature of core-type DNA recognition by the
      bivalent recombinases of the lambda Int family.

PMID- 11827962
TI  - The human immunodeficiency virus-1 Tat protein activates human umbilical vein
      endothelial cell E-selectin expression via an NF-kappa B-dependent mechanism.
AB  - Human immunodeficiency virus infection is associated with inflammation and
      endothelial cell activation that cannot be ascribed to direct infection by the
      virus or to the presence of opportunistic infections. Factors related to the
      virus itself, to the host and/or to environmental exposures probably account for
      these observations. The HIV protein Tat, a viral regulator required for efficient
      transcription of the viral genome in host cells is secreted from infected cells
      and taken up by uninfected by-stander cells. Tat can also act as a general
      transcriptional activator of key inflammatory molecules. We have examined whether
      Tat contributes to this endothelial cell activation by activating NF-kappaB.
      Human endothelial cells exposed to Tat in the culture medium activated E-selectin
      expression with delayed kinetics compared with tumor necrosis factor (TNF). Tat
      mediated E-selectin up-regulation required the basic domain of Tat and was
      inhibited by a Tat antibody. Transfection of human E-selectin promoter-luciferase
      reporter constructs into Tat-bearing cells or into endothelial cells co
      transfected with a Tat expression vector resulted in induction of luciferase
      expression. Either Tat or TNF activated p65 translocation and binding to an
      oligonucleotide containing the E-selectin kappaB site 3 sequence. Tat-mediated
      p65 translocation was also delayed compared with TNF. Neither agent induced new
      synthesis of p65. A super-repressor adenovirus (AdIkappaBalphaSR) that
      constitutively sequesters IkappaB in the cytoplasm as well as cycloheximide or
      actinomycin D inhibited Tat- or TNF-mediated kappaB translocation and E-selectin
      up-regulation.

PMID- 11827963
TI  - Functions of sensor 1 and sensor 2 regions of Saccharomyces cerevisiae Cdc6p in
      vivo and in vitro.
AB  - Cdc6p is a key regulator of the cell cycle in eukaryotes and is a member of the
      AAA(+) (ATPases associated with a variety of cellular activities) family of
      proteins. In this family of proteins, the sensor 1 and sensor 2 regions are
      important for their function and ATPase activity. Here, site-directed mutagenesis
      has been used to examine the role of these regions of Saccharomyces cerevisiae
      Cdc6p in controlling the cell cycle progression and initiation of DNA
      replication. Two important amino acid residues (Asn(263) in sensor 1 and Arg(332)
      in sensor 2) were identified as key residues for Cdc6p function in vivo. Cells
      expressing mutant Cdc6p (N263A or R332E) grew slowly and accumulated in the S
      phase. In cells expressing mutant Cdc6p, loading of the minichromosome
      maintenance (MCM) complex of proteins was decreased, suggesting that the slow
      progression of S phase in these cells was due to inefficient MCM loading on
      chromatin. Purified wild type Cdc6p but not mutant Cdc6p (N263A and R332E) caused
      the structural modification of origin recognition complex proteins. These results
      are consistent with the idea that Cdc6p uses its ATPase activity to change the
      conformation of origin recognition complex, and then together they recruit the
      MCM complex.

PMID- 11827964
TI  - Folding of the Plasmodium falciparum cysteine protease falcipain-2 is mediated by
      a chaperone-like peptide and not the prodomain.
AB  - Papain-family cysteine proteases of the malaria parasite Plasmodium falciparum,
      known as falcipains, are hemoglobinases and potential drug targets. Available
      data suggest that papain-family proteases require prodomains for correct folding
      into functional conformations. However, in prior studies of falcipain-2, an
      Escherichia coli-expressed construct containing only a small portion of the
      prodomain refolded efficiently, suggesting that this enzyme differs in this
      regard from other papain-family enzymes. To better characterize the determinants
      of folding for falcipain-2, we expressed multiple pro- and mature constructs of
      the enzyme in E. coli and assessed their abilities to refold. Mature falcipain-2
      refolded into active protease with very similar properties to those of proteins
      resulting from the refolding of proenzyme constructs. Deletion of a 17-amino acid
      amino-terminal segment of the mature protease yielded a construct incapable of
      correct folding, but inclusion of this segment in trans allowed folding to active
      falcipain-2. The prodomain was a potent, competitive, and reversible inhibitor of
      mature falcipain-2 (K(i) 10(-10) m). Our results identify a chaperone-like
      function of an amino-terminal segment of mature falcipain-2 and suggest that
      protease inhibition, but not the mediation of folding, is a principal function of
      the falcipain-2 prodomain.

PMID- 11827965
TI  - Molecular cloning and characterization of sphingolipid ceramide N-deacylase from
      a marine bacterium, Shewanella alga G8.
AB  - Recently, lyso-sphingolipids have been identified as ligands for several orphan G
      protein-coupled receptors, although the molecular mechanism for their generation
      has yet to be clarified. Here, we report the molecular cloning of the enzyme,
      which catalyzes the generation of lyso-sphingolipids from various sphingolipids
      (sphingolipid ceramide N-deacylase). The 75-kDa enzyme was purified from the
      marine bacterium, Shewanella alga G8, and its gene was cloned from a G8 genomic
      library using sequences of the purified enzyme. The cloned enzyme was composed of
      992 amino acids, including a signal sequence of 35 residues, and its molecular
      weight was estimated to be 109,843. Significant sequence similarities were found
      with an unknown protein of Streptomyces fradiae Y59 and a Lumbricus terrestris
      lectin but not other known functional proteins. The 106-kDa recombinant enzyme
      expressed in Escherichia coli hydrolyzed various glycosphingolipids and
      sphingomyelin, although it seems to be much less active than the native 75-kDa
      enzyme. In vitro translation using wheat germ extract revealed the activity of a
      75-kDa deletion mutant lacking a C terminus to be much stronger than that of the
      full-length enzyme, suggesting that C-terminal processing is necessary for full
      activity.

PMID- 11827966
TI  - H2O2 induces a transient multi-phase cell cycle arrest in mouse fibroblasts
      through modulating cyclin D and p21Cip1 expression.
AB  - To defend against the potential damages induced by reactive oxygen species,
      proliferating cells enter a transient cell cycle arrest. We treated mouse
      fibroblasts with H(2)O(2) and found that sublethal doses of H(2)O(2) induced a
      transient multi-phase cell cycle arrest at the G(1), S, and G(2) phases but not
      the M phase. Western blot analysis demonstrated that this transient cell cycle
      arrest is associated with the down-regulation of cyclins D1 and D3 and up
      regulation of the CKI p21(Cip1) expression. We also demonstrate that the
      induction in p21(Cip1) expression by H(2)O(2) is at least partially mediated at
      the transcriptional level and can occur in the absence of p53 function. Further
      immunoprecipitation kinase and immunodepletion assays indicated that in response
      to H(2)O(2) treatment, the down-regulation of cyclin Ds expression are associated
      with repression of cyclin D-CDK4, whereas the accumulation of p21(Cip1) is
      responsible for the inhibition of cyclin E and A-CDK2 activity and associated
      with the down-regulation of cyclin B-CDC2 activity. These data could account for
      the cell cycle arrest at the G(1), S, and G(2) phases following H(2)O(2)
      stimulation. Deletion of p21(Cip1), restoration of cyclin D expression, or
      overexpression of cyclin E alone is insufficient to effectively overcome the cell
      cycle arrest caused by sublethal doses of H(2)O(2). By contrast, overexpression
      of the human Herpesvirus 8 K cyclin, which can mimic the function of cyclin D and
      E, is enough to override this transient cell cycle arrest. On the basis of our
      findings, we propose a model in which moderate levels of H(2)O(2) induce a
      transient multi-phase cell cycle arrest at least partially through up-regulation
      of p21(Cip1) and down-regulation of cyclin D expression.

PMID- 11827967
TI  - Molecular characterization of a specific thiamine triphosphatase widely expressed
      in mammalian tissues.
AB  - Thiamine triphosphate (ThTP) is found at low concentrations in most animal
      tissues, and recent data suggest that it may act as a phosphate donor for the
      phosphorylation of some proteins. In the mammalian brain, ThTP synthesis is
      rapid, but its steady-state concentration remains low, presumably because of
      rapid hydrolysis. In this report we purified a soluble thiamine triphosphatase
      (ThTPase; EC ) from calf brain. The bovine ThTPase is a 24-kDa monomer,
      hydrolyzing ThTP with virtually absolute specificity. Partial sequence data
      obtained from the purified bovine enzyme by tandem mass spectrometry were used to
      search the GenBank data base. A significant identity was found with only one
      human sequence, the hypothetical 230-amino acid protein MGC2652. The coding
      regions from human and bovine brain mRNA were amplified by reverse transcription
      PCR, cloned in Escherichia coli, and sequenced. The human open reading frame was
      expressed in E. coli as a GST fusion protein. Transformed bacteria had a high
      isopropyl-beta-d-thiogalactopyranoside-inducible ThTPase activity. The
      recombinant ThTPase had properties similar to those of human brain ThTPase, and
      it was specific for ThTP. The mRNA was expressed in most human tissues but at
      relatively low levels. This is the first report of a molecular characterization
      of a specific ThTPase.

PMID- 11827968
TI  - Exposure of cryptic domains in the alpha 1-chain of laminin-1 by elastase
      stimulates macrophages urokinase and matrix metalloproteinase-9 expression.
AB  - Degradation of the extracellular matrix leads to the release of fragments, which
      elicit biological responses distinct from intact molecules. We have reported that
      alpha1:Ser(2091)-Arg(2108), a peptide derived from the alpha1-chain of laminin-1,
      triggers protein kinase C-dependent activation of MAPK(erk1/2), leading to the up
      regulation of macrophage urokinase type plasminogen activator and matrix
      metalloproteinase (MMP)-9 expression. Since intact laminin-1 failed to trigger
      these events, we hypothesized that alpha1:Ser(2091)-Arg(2108) is cryptic or
      assumes a conformation not recognized by macrophages. Here we demonstrate that
      elastase cleavage of laminin-1 generates fragments, which stimulate proteinase
      expression by RAW264.7 macrophages and peritoneal macrophages. In contrast,
      fragments generated by MMP-2, MMP-7, or plasmin had no effect on macrophage
      proteinase expression. Elastase-generated laminin-1 fragments were fractionated
      by heparin-Sepharose chromatography. Heparin-binding fragments stimulated
      macrophages' proteinase expression severalfold greater than nonbinding fragments.
      The heparin binding fragments reacted with antibodies directed against regions of
      the alpha1-chain including alpha1:Ser(2091)-Arg(2108) and the globular domain. A
      peptide from the first loop of the globular domain (alpha1:Ser(2179)-Ser(2198))
      triggered the phosphorylation of MAPK(erk1/2) and stimulated the expression of
      macrophage urokinase type plasminogen activator and MMP-9. Moreover, a heparin
      binding fraction isolated from an aortic aneurysm contained fragments of alpha1
      chain and stimulated macrophages' proteinase expression. Based on these data, we
      conclude that cryptic domains in the COOH-terminal portion of the alpha1-chain of
      laminin are exposed by proteolysis and stimulate macrophages' proteinase
      expression.

PMID- 11827969
TI  - Tissue inhibitor of metalloproteinase-3 induces a Fas-associated death domain
      dependent type II apoptotic pathway.
AB  - Tissue inhibitors of metalloproteinases (TIMPs) are important regulators of
      matrix metalloproteinase (MMP) and adamalysin metalloproteinase activity. We
      previously reported that overexpression of TIMP-3 inhibits MMPs and induces
      apoptotic cell death in a variety of cell types and demonstrated that apoptosis
      is mediated through the N terminus of TIMP-3, which harbors the MMP inhibitory
      domain. However, little is known about the mechanisms underlying TIMP-3-induced
      apoptosis. Here we demonstrate that overexpression of TIMP-3 induced activation
      of initiator caspase-8 and -9 and promoted caspase-mediated cleavage of the death
      substrates poly(ADP-ribose) polymerase and focal adhesion kinase. Furthermore,
      TIMP-3 induced mitochondrial activation as demonstrated by loss of mitochondrial
      membrane potential and release of cytochrome c. Intervention studies demonstrated
      that overexpression of Bcl-2, the anti-apoptotic mitochondrial membrane protein,
      or CrmA, a viral serpin inhibitor of caspase-8, completely inhibited TIMP-3
      induced apoptosis. Furthermore, a dominant-negative Fas-associated death domain
      mutant inhibited TIMP-3-induced death substrate cleavage and apoptotic death.
      Taken together, these results indicate that TIMP-3 overexpression induces a type
      II apoptotic pathway initiated via a Fas-associated death domain-dependent
      mechanism.

PMID- 11827971
TI  - Evolutionary relationship between different subgroups of restriction
      endonucleases.
AB  - The type II restriction endonuclease SsoII shows sequence similarity with 10
      other restriction endonucleases, among them the type IIE restriction endonuclease
      EcoRII, which requires binding to an effector site for efficient DNA cleavage,
      and the type IIF restriction endonuclease NgoMIV, which is active as a
      homotetramer and cleaves DNA with two recognition sites in a concerted reaction.
      We show here that SsoII is an orthodox type II enzyme, which is active as a
      homodimer and does not require activation by binding to an effector site.
      Nevertheless, it shares with EcoRII and NgoMIV a very similar DNA-binding site
      and catalytic center as shown here by a mutational analysis, indicative of an
      evolutionary relationship between these three enzymes. We suggest that a similar
      relationship exists between other orthodox type II, type IIE, and type IIF
      restriction endonucleases. This may explain why similarities may be more
      pronounced between members of different subtypes of restriction enzymes than
      among the members of a given subtype.

PMID- 11827970
TI  - 8-Isoprostaglandin E2 enhances receptor-activated NFkappa B ligand (RANKL)
      dependent osteoclastic potential of marrow hematopoietic precursors via the cAMP
      pathway.
AB  - Lipid oxidation products promote atherosclerosis and may also affect
      osteoporosis. We showed previously that oxidized lipids including 8
      isoprostaglandin E2 (isoPGE2) inhibit osteoblastic differentiation of
      preosteoblasts. Since osteoporosis is mediated both by decreased osteoblastic
      bone formation and by increased osteoclastic bone resorption, we assessed whether
      oxidized lipids regulate the osteoclastic potential of marrow hematopoietic
      cells. Treatment of marrow-derived preosteoclasts with isoPGE2 enhanced
      osteoclastic differentiation as evidenced by increased tartrate-resistant acid
      phosphatase (TRAP) activity and multinucleation, which were inhibited by
      calcitonin, and increased numbers of resorption pits. The enhanced osteoclastic
      differentiation by isoPGE2 was observed whether preosteoclasts were in coculture
      with stromal cells or in monoculture in the presence of receptor-activated
      NFkappaB ligand (RANKL) and macrophage colony-stimulating factor. Receptor
      antagonist studies suggest that isoPGE2 effects were mediated by prostaglandin
      receptor subtypes EP2/DP on preosteoclasts and subtype EP1 and thromboxane
      receptors on stromal/osteoblast cells. The enhanced TRAP activity was also
      inhibited by cAMP-dependent protein kinase inhibitors, and isoPGE2 elevated
      intracellular cAMP levels of preosteoclast monocultures. Other oxidized lipids
      also enhanced the TRAP activity of preosteoclast monocultures. These data suggest
      that isoPGE2 enhances osteoclastic differentiation of marrow preosteoclasts and
      that this regulation occurs via the cAMP-dependent protein kinase pathway.

PMID- 11827972
TI  - MICAL, a novel CasL interacting molecule, associates with vimentin.
AB  - CasL/HEF1 belongs to the p130(Cas) family. It is tyrosine-phosphorylated
      following beta(1) integrin and/or T cell receptor stimulation and is thus
      considered to be important for immunological reactions. CasL has several
      structural motifs such as an SH3 domain and a substrate domain and interacts with
      many molecules through these motifs. To obtain more insights on the CasL-mediated
      signal transduction, we sought proteins that interact with the CasL SH3 domain by
      far Western screening, and we identified a novel human molecule, MICAL (a
      Molecule Interacting with CasL). MICAL is a protein of 118 kDa and is expressed
      in the thymus, lung, spleen, kidney, testis, and hematopoietic cells. MICAL has a
      calponin homology domain, a LIM domain, a putative leucine zipper motif, and a
      proline-rich PPKPP sequence. MICAL associates with CasL through this PPKPP
      sequence. MICAL is a cytoplasmic protein and colocalizes with CasL at the
      perinuclear area. Through the COOH-terminal region, MICAL also associates with
      vimentin that is a major component of intermediate filaments. Immunostaining
      revealed that MICAL localizes along with vimentin intermediate filaments. These
      results suggest that MICAL may be a cytoskeletal regulator that connects CasL to
      intermediate filaments.

PMID- 11827973
TI  - Lack of the small plastid-encoded PsbJ polypeptide results in a defective water
      splitting apparatus of photosystem II, reduced photosystem I levels, and
      hypersensitivity to light.
AB  - Photosystem II is a large pigment-protein complex catalyzing water oxidation and
      initiating electron transfer processes across the thylakoid membrane. In addition
      to large protein subunits, many of which bind redox cofactors, photosystem II
      particles contain a number of low molecular weight polypeptides whose function is
      only poorly defined. Here we have investigated the function of one of the
      smallest polypeptides in photosystem II, PsbJ. Using a reverse genetics approach,
      we have inactivated the psbJ gene in the tobacco chloroplast genome. We show
      that, although the PsbJ polypeptide is not principally required for functional
      photosynthetic electron transport, plants lacking PsbJ are unable to grow
      photoautotrophically. We provide evidence that this is due to the accumulation of
      incompletely assembled water-splitting complexes, which in turn causes
      drastically reduced photosynthetic performance and extreme hypersensitivity to
      light. Our results suggest a role of PsbJ for the stable assembly of the water
      splitting complex of photosystem II and, in addition, support a control of
      photosystem I accumulation through photosystem II activity.

PMID- 11827974
TI  - Phoneutria nigriventer omega-phonetoxin IIA blocks the Cav2 family of calcium
      channels and interacts with omega-conotoxin-binding sites.
AB  - omega-Phonetoxin IIA (omegaPtxIIA), a peptide from spider venom (Phoneutria
      nigriventer), inhibits high threshold voltage-dependent calcium currents in
      neurons. To define its pharmacological specificity, we have used patch-clamp
      methods in cell lines expressing recombinant Ca(v)2.1, Ca(v)2.2, and Ca(v)2.3
      channels (P/Q-, N-, and R-type currents, respectively). Calcium currents
      generated by Ca(v)2.1 and Ca(v)2.2 were blocked almost irreversibly by 3 nm
      omegaPtxIIA, whereas Ca(v)2.3 showed partial and readily reversible inhibition.
      Binding assays with mono[(125)I]iodo-omegaPtxIIA indicated that membranes
      expressing recombinant Ca(v)2.1 or Ca(v)2.2 channels showed a single class of
      sites with similar affinity (K(D) approximately 50 pm), whereas low affinity
      interactions were detectable with Ca(v)2.3. Kinetic, saturation, and displacement
      assays demonstrated that rat brain synaptosomes displayed multiple classes of
      binding sites for (125)I-omegaPtxIIA. High affinity binding of (125)I-omegaPtxIIA
      was totally displaced by omegaPtxIIA (K(i) = 100 pm), but only partially by omega
      conotoxin GVIA (25% inhibition) and omega-conotoxin MVIIC (50% inhibition at 0.3
      microm). (125)I-omegaPtxIIA thus defines a unique high affinity binding site that
      is predominantly associated with Ca(v)2.1 or Ca(v)2.2 channels.

PMID- 11827976
TI  - Intracellular coupling of the heavy chain of pre-alpha-inhibitor to chondroitin
      sulfate.
AB  - Pre-alpha-inhibitor is a serum protein consisting of two polypeptides, the heavy
      chain and bikunin, covalently linked through an ester bond between the
      chondroitin sulfate chain of bikunin and the alpha-carboxyl group of the carboxyl
      terminal residue of the heavy chain. The heavy chain is synthesized with a
      carboxyl-terminal extension, which is cleaved off just before the link to bikunin
      is formed. Our earlier studies indicate that this extension mediates the
      cleavage, and we have now found that a short segment on the amino-terminal side
      of the cleavage site is also required for the reaction. Furthermore, we
      previously showed that coexpression of the heavy chain precursor and bikunin in
      COS-1 cells leads to linkage, and we have now used this system to identify a His
      residue in the carboxyl-terminal extension that is specifically required for the
      intracellular coupling of the two proteins. In addition, we have shown that
      another chondroitin sulfate-containing protein, decorin, will also form a complex
      with the heavy chain, as will free chondroitin sulfate chains. These results
      suggest that in vivo there might be other, as yet unknown, chondroitin sulfate
      containing polypeptides linked to the heavy chain.

PMID- 11827975
TI  - Activation of TRPV4 channels (hVRL-2/mTRP12) by phorbol derivatives.
AB  - We have studied activation by phorbol derivatives of TRPV4 channels, the human
      VRL-2, and murine TRP12 channels, which are highly homologous to the human VR
      OAC, and the human and murine OTRPC4 channel. 4alpha-Phorbol 12,13-didecanoate
      (4alpha-PDD) induced an increase in intracellular Ca(2+) concentration,
      [Ca(2+)](i), in 1321N1 cells stably transfected with human VRL-2 (hVRL-2.1321N1)
      or HEK-293 cells transiently transfected with murine TRP12, but not in
      nontransfected or mock-transfected cells. Concomitantly with the increase in
      [Ca(2+)](i), 4alpha-PDD activated an outwardly rectifying cation channel with an
      Eisenman IV permeation sequence for monovalent cations that is Ca(2+)-permeable
      with P(Ca)/P(Na) = 5.8. Phorbol 12-myristate 13-acetate also induced an increase
      in [Ca(2+)](i) but was approximately 50 times less effective than 4alpha-PDD.
      EC(50) for Ca(2+) increase and current activation was nearly identical (pEC(50)
      approximately 6.7). Similar effects were observed in freshly isolated mouse aorta
      endothelial cells which express TRP12 endogenously. By using 4alpha-PDD as a tool
      to stimulate TRP12, we showed that activation of this channel is modulated by
      [Ca(2+)](i); an increase in [Ca(2+)](i) inhibits the channel with an IC(50) of
      406 nm. Ruthenium Red at a concentration of 1 microm completely blocks inward
      currents at -80 mV but has a smaller effect on outward currents likely indicating
      a voltage dependent channel block. We concluded that the phorbol derivatives
      activate TRPV4 (VR-OAC, VRL-2, OTRPC4, TRP12) independently from protein kinase
      C, in a manner consistent with direct agonist gating of the channel.

PMID- 11827977
TI  - Expression of L-histidine decarboxylase in mouse male germ cells.
AB  - Histamine synthesis in male reproductive tissues remains largely unknown. The
      interaction between stem cell factor and its receptor, c-Kit, has been found to
      be essential for the maturation of male germ cells and peripheral mast cells.
      Based on this analogy, we investigated the expression of histidine decarboxylase
      (HDC), the rate-limiting enzyme of histamine synthesis, in mouse male germ cells.
      Immunohistochemical analyses revealed that HDC is localized in the acrosomes of
      spermatids and spermatozoa. In the testis, epididymis, and spermatozoa, a
      significant amount of histamine and HDC activity were detected. W/W(V) mice,
      known to lack most of their germ cells in the seminiferous tubules, were found to
      lack HDC protein expression as well as HDC activity in the testis. An in vitro
      acrosome reaction induced by a calcium ionophore, caused the release of histamine
      from epididymal spermatozoa. Our observations indicate that histamine is produced
      in and released from the acrosomes.

PMID- 11827978
TI  - Assembly of human hemoglobin (Hb) beta- and gamma-globin chains expressed in a
      cell-free system with alpha-globin chains to form Hb A and Hb F.
AB  - Rates of in vitro synthesis of radiolabeled gamma and beta chains made in a cell
      free transcription/translation system were similar, but expressed globin chains
      were unstable. The addition of unlabeled beta or gamma chains at the start of
      chain synthesis generated radiolabeled beta(4) or gamma(2) and gamma(4) chains,
      respectively. If unlabeled alpha-globin chains were added at the start of chain
      synthesis, then approximately equal amounts of radiolabeled alphabeta or
      alphagamma bands were generated. If unlabeled Hb A or Hb F was added to reactions
      containing radiolabeled alphabeta or alphagamma prior to electrophoresis, then
      radiolabeled Hb A or Hb F tetramers, respectively, were generated. If alpha
      chains were added after synthesis of radiolabeled gamma chains made in the
      presence of unlabeled gamma chains, then little radiolabeled alphagamma formed.
      In contrast, if alpha chains were added after synthesis of radiolabeled beta
      chains made in the presence of unlabeled beta chains, then radiolabeled
      alpha(2)beta(2) formed. These findings suggest that beta and gamma chains
      associate with alpha chains during or soon after translation. This would prevent
      the formation of unstable monomers as well as stable gamma(2) dimers and suggests
      that alpha chains may bind to nascent non-alpha chains, acting as folding
      catalysts to promote functional tetrameric hemoglobin formation in vivo.

PMID- 11827979
TI  - Hitchhiking fads en route to peroxisomes.
AB  - A unique aspect of protein translocation across the peroxisomal membrane is that
      folded and oligomeric proteins get across this membrane (Purdue and Lazarow,
      2001). The generality of this rule, its specific features, and its mechanism are
      not fully understood. A paper in this issue addresses, in a very thorough
      fashion, the assembly, cofactor binding, and import of an oligomeric protein,
      acyl-CoA oxidase (Aox), into the peroxisome matrix (Titorenko et al., 2002, this
      issue).

PMID- 11827980
TI  - Disassembly of interchromatin granule clusters alters the coordination of
      transcription and pre-mRNA splicing.
AB  - To examine the involvement of interchromatin granule clusters (IGCs) in
      transcription and pre-mRNA splicing in mammalian cell nuclei, the serine-arginine
      (SR) protein kinase cdc2-like kinase (Clk)/STY was used as a tool to manipulate
      IGC integrity in vivo. Both immunofluorescence and transmission electron
      microscopy analyses of cells overexpressing Clk/STY indicate that IGC components
      are completely redistributed to a diffuse nuclear localization, leaving no
      residual structure. Conversely, overexpression of a catalytically inactive
      mutant, Clk/STY(K190R), causes retention of hypophosphorylated SR proteins in
      nuclear speckles. Our data suggest that the protein-protein interactions
      responsible for the clustering of interchromatin granules are disrupted when SR
      proteins are hyperphosphorylated and stabilized when SR proteins are
      hypophosphorylated. Interestingly, cells without intact IGCs continue to
      synthesize nascent transcripts. However, both the accumulation of splicing
      factors at sites of pre-mRNA synthesis as well as pre-mRNA splicing are
      dramatically reduced, demonstrating that IGC disassembly perturbs coordination
      between transcription and pre-mRNA splicing in mammalian cell nuclei.

PMID- 11827981
TI  - Drosophila Aurora A kinase is required to localize D-TACC to centrosomes and to
      regulate astral microtubules.
AB  - Disruption of the function of the A-type Aurora kinase of Drosophila by mutation
      or RNAi leads to a reduction in the length of astral microtubules in syncytial
      embryos, larval neuroblasts, and cultured S2 cells. In neuroblasts, it can also
      lead to loss of an organized centrosome and its associated aster from one of the
      spindle poles, whereas the centrosome at the other pole has multiple centrioles.
      When centrosomes are present at the poles of aurA mutants or aurA RNAi spindles,
      they retain many antigens but are missing the Drosophila counterpart of mammalian
      transforming acidic coiled coil (TACC) proteins, D-TACC. We show that a
      subpopulation of the total Aurora A is present in a complex with D-TACC, which is
      a substrate for the kinase. We propose that one of the functions of Aurora A
      kinase is to direct centrosomal organization such that D-TACC complexed to the
      MSPS/XMAP215 microtubule-associated protein may be recruited, and thus modulate
      the behavior of astral microtubules.

PMID- 11827982
TI  - The yeast protein kinase Mps1p is required for assembly of the integral spindle
      pole body component Spc42p.
AB  - Saccharomyces cerevisiae MPS1 encodes an essential protein kinase that has roles
      in spindle pole body (SPB) duplication and the spindle checkpoint. Previously
      characterized MPS1 mutants fail in both functions, leading to aberrant DNA
      segregation with lethal consequences. Here, we report the identification of a
      unique conditional allele, mps1-8, that is defective in SPB duplication but not
      the spindle checkpoint. The mutations in mps1-8 are in the noncatalytic region of
      MPS1, and analysis of the mutant protein indicates that Mps1-8p has wild-type
      kinase activity in vitro. A screen for dosage suppressors of the mps1-8
      conditional growth phenotype identified the gene encoding the integral SPB
      component SPC42. Additional analysis revealed that mps1-8 exhibits synthetic
      growth defects when combined with certain mutant alleles of SPC42. An epitope
      tagged version of Mps1p (Mps1p-myc) localizes to SPBs and kinetochores by
      immunofluorescence microscopy and immuno-EM analysis. This is consistent with the
      physical interaction we detect between Mps1p and Spc42p by coimmunoprecipitation.
      Spc42p is a substrate for Mps1p phosphorylation in vitro, and Spc42p
      phosphorylation is dependent on Mps1p in vivo. Finally, Spc42p assembly is
      abnormal in a mps1-1 mutant strain. We conclude that Mps1p regulates assembly of
      the integral SPB component Spc42p during SPB duplication.

PMID- 11827983
TI  - Visualization of Rab9-mediated vesicle transport from endosomes to the trans
      Golgi in living cells.
AB  - Mannose 6-phosphate receptors (MPRs) are transported from endosomes to the trans
      Golgi via a transport process that requires the Rab9 GTPase and the cargo adaptor
      TIP47. We have generated green fluorescent protein variants of Rab9 and
      determined their localization in cultured cells. Rab9 is localized primarily in
      late endosomes and is readily distinguished from the trans-Golgi marker
      galactosyltransferase. Coexpression of fluorescent Rab9 and Rab7 revealed that
      these two late endosome Rabs occupy distinct domains within late endosome
      membranes. Cation-independent mannose 6-phosphate receptors are enriched in the
      Rab9 domain relative to the Rab7 domain. TIP47 is likely to be present in this
      domain because it colocalizes with the receptors in fixed cells, and a TIP47
      mutant disrupted endosome morphology and sequestered MPRs intracellularly. Rab9
      is present on endosomes that display bidirectional microtubule-dependent
      motility. Rab9-positive transport vesicles fuse with the trans-Golgi network as
      followed by video microscopy of live cells. These data provide the first
      indication that Rab9-mediated endosome to trans-Golgi transport can use a vesicle
      (rather than a tubular) intermediate. Our data suggest that Rab9 remains vesicle
      associated until docking with the Golgi complex and is rapidly removed
      concomitant with or just after membrane fusion.

PMID- 11827984
TI  - Nectin: an adhesion molecule involved in formation of synapses.
AB  - The nectin-afadin system is a novel cell-cell adhesion system that organizes
      adherens junctions cooperatively with the cadherin-catenin system in epithelial
      cells. Nectin is an immunoglobulin-like adhesion molecule, and afadin is an actin
      filament-binding protein that connects nectin to the actin cytoskeleton. Nectin
      has four isoforms (-1, -2, -3, and -4). Each nectin forms a homo-cis-dimer
      followed by formation of a homo-trans-dimer, but nectin-3 furthermore forms a
      hetero-trans-dimer with nectin-1 or -2, and the formation of each hetero-trans
      dimer is stronger than that of each homo-trans-dimer. We show here that at the
      synapses between the mossy fiber terminals and dendrites of pyramidal cells in
      the CA3 area of adult mouse hippocampus, the nectin-afadin system colocalizes
      with the cadherin-catenin system, and nectin-1 and -3 asymmetrically localize at
      the pre- and postsynaptic sides of puncta adherentia junctions, respectively.
      During development, nectin-1 and -3 asymmetrically localize not only at puncta
      adherentia junctions but also at synaptic junctions. Inhibition of the nectin
      based adhesion by an inhibitor of nectin-1 in cultured rat hippocampal neurons
      results in a decrease in synapse size and a concomitant increase in synapse
      number. These results indicate an important role of the nectin-afadin system in
      the formation of synapses.

PMID- 11827985
TI  - Myelin-associated glycoprotein and myelin galactolipids stabilize developing axo
      glial interactions.
AB  - We have analyzed mice that lack both the myelin-associated glycoprotein (MAG) and
      the myelin galactolipids, two glial components implicated in mediating axo-glial
      interactions during the myelination process. The single-mutant mice produce
      abnormal myelin containing similar ultrastructural abnormalities, suggesting that
      these molecules may play an overlapping role in myelin formation. Furthermore,
      the absence of the galactolipids results in a disruption in paranodal axo-glial
      interactions, and we show here that similar, albeit less severe, abnormalities
      exist in the developing MAG mutant. In the double-mutant mice, maintenance of axo
      glial adhesion is significantly more affected than in the single mutants,
      supporting the overlapping function hypothesis. We also show that independently
      of MAG, galactolipids, and paranodal junctional components, immature nodes of
      Ranvier form normally, but rapidly destabilize in their absence. These data
      indicate that distinct molecular mechanisms are responsible for the formation and
      maintenance of axo-glial interactions.

PMID- 11827986
TI  - The challenge of target sequence specificity in C-->U RNA editing.

PMID- 11827987
TI  - Activation and inhibition of lymphocytes by costimulation.

PMID- 11827989
TI  - Tumor immunotherapy: inching toward the finish line.

PMID- 11827988
TI  - Adapters in lymphocyte signaling.

PMID- 11827990
TI  - Putting the neo into neoangiogenesis.

PMID- 11827991
TI  - Effects of reduced mucus oxygen concentration in airway Pseudomonas infections of
      cystic fibrosis patients.
AB  - Current theories of CF pathogenesis predict different predisposing "local
      environmental" conditions and sites of bacterial infection within CF airways.
      Here we show that, in CF patients with established lung disease, Pseudomonas
      aeruginosa was located within hypoxic mucopurulent masses in airway lumens. In
      vitro studies revealed that CF-specific increases in epithelial O(2) consumption,
      linked to increased airway surface liquid (ASL) volume absorption and mucus
      stasis, generated steep hypoxic gradients within thickened mucus on CF epithelial
      surfaces prior to infection. Motile P. aeruginosa deposited on CF airway surfaces
      penetrated into hypoxic mucus zones and responded to this environment with
      increased alginate production. With P. aeruginosa growth in oxygen restricted
      environments, local hypoxia was exacerbated and frank anaerobiosis, as detected
      in vivo, resulted. These studies indicate that novel therapies for CF include
      removal of hypoxic mucus plaques and antibiotics effective against P. aeruginosa
      adapted to anaerobic environments.

PMID- 11827992
TI  - Arteriolar and venular patterning in retinas of mice selectively expressing VEGF
      isoforms.
AB  - The murine VEGF gene is alternatively transcribed to yield the VEGF(120),
      VEGF(164), and VEGF(188) isoforms, which differ in their potential to bind to
      heparan sulfate and neuropilin-1 and to stimulate endothelial growth. Here, their
      role in retinal vascular development was studied in mice selectively expressing
      single isoforms. VEGF(164/164) mice were normal, healthy, and had normal retinal
      angiogenesis. In contrast, VEGF(120/120) mice exhibited severe defects in
      vascular outgrowth and patterning, whereas VEGF(188/188) mice displayed normal
      venular outgrowth but impaired arterial development. It is noteworthy that
      neuropilin-1, a receptor for VEGF(164), was predominantly expressed in retinal
      arterioles. These findings reveal distinct roles of the various VEGF isoforms in
      vascular patterning and arterial development in the retina.

PMID- 11827994
TI  - Muscle-specific inactivation of the IGF-I receptor induces compensatory
      hyperplasia in skeletal muscle.
AB  - During the development of skeletal muscle, myoblasts withdraw from the cell cycle
      and differentiate into myotubes. The insulin-like growth factors IGF-I and IGF
      II, through their cognate tyrosine kinase receptor (IGF-I receptor), are known to
      play a role in this process. After withdrawal of myoblasts from the cell cycle,
      IGF-I promotes muscle differentiation by inducing the expression or activity of
      myogenic regulatory factors (MyoD, myogenin) and effectors (p21). However, little
      is known about the intracellular mechanisms by which the IGF-I system regulates
      these factors during the process of myogenesis. Here we show that MKR mice, which
      express a dominant negative IGF-I receptor specifically in skeletal muscle, have
      marked muscle hypoplasia from birth to 3 weeks of age. This hypoplasia occurs
      concomitantly with a decrease in ERK immunoreactivity levels and decreases in
      MyoD and myogenin expression. BrdU immunocytochemistry showed a compensatory
      hyperplasia as MKR mice grew to adulthood. Interestingly, hyperplasia occurred
      concomitantly with an increase in p38, MyoD, myogenin, and p21 immunoreactivity
      levels, as well as a decrease in Twist levels. These findings suggest that
      regulation of these cellular elements by IGF-I may play a role in the development
      and differentiation of skeletal muscle in vivo.

PMID- 11827993
TI  - Origin of endothelial progenitors in human postnatal bone marrow.
AB  - This study demonstrates that a CD34(-), vascular endothelial cadherin(-) (VE
      cadherin(-)), AC133(+), and fetal liver kinase(+) (Flk1(+)) multipotent adult
      progenitor cell (MAPC) that copurifies with mesenchymal stem cells from postnatal
      human bone marrow (BM) is a progenitor for angioblasts. In vitro, MAPCs cultured
      with VEGF differentiate into CD34(+), VE-cadherin(+), Flk1(+) cells - a phenotype
      that would be expected for angioblasts. They subsequently differentiate into
      cells that express endothelial markers, function in vitro as mature endothelial
      cells, and contribute to neoangiogenesis in vivo during tumor angiogenesis and
      wound healing. This in vitro model of preangioblast-to-endothelium
      differentiation should prove very useful in studying commitment to the angioblast
      and beyond. In vivo, MAPCs can differentiate in response to local cues into
      endothelial cells that contribute to neoangiogenesis in tumors. Because MAPCs can
      be expanded in culture without obvious senescence for more than 80 population
      doublings, they may be an important source of endothelial cells for cellular pro-
      or anti-angiogenic therapies.

PMID- 11827995
TI  - Constitutively active AMP kinase mutations cause glycogen storage disease
      mimicking hypertrophic cardiomyopathy.
AB  - Mutations in PRKAG2, the gene for the gamma 2 regulatory subunit of AMP-activated
      protein kinase, cause cardiac hypertrophy and electrophysiologic abnormalities,
      particularly preexcitation (Wolff-Parkinson-White syndrome) and atrioventricular
      conduction block. To understand the mechanisms by which PRKAG2 defects cause
      disease, we defined novel mutations, characterized the associated cardiac
      histopathology, and studied the consequences of introducing these mutations into
      the yeast homologue of PRKAG2, Snf4. Although the cardiac pathology caused by
      PRKAG2 mutations Arg302Gln, Thr400Asn, and Asn488Ile include myocyte enlargement
      and minimal interstitial fibrosis, these mutations were not associated with
      myocyte and myofibrillar disarray, the pathognomonic features of hypertrophic
      cardiomyopathy caused by sarcomere protein mutations. Instead PRKAG2 mutations
      caused pronounced vacuole formation within myocytes. Several lines of evidence
      indicated these vacuoles were filled with glycogen-associated granules. Analyses
      of the effects of human PRKAG2 mutations on Snf1/Snf4 kinase function
      demonstrated constitutive activity, which could foster glycogen accumulation.
      Taken together, our data indicate that PRKAG2 mutations do not cause hypertrophic
      cardiomyopathy but rather lead to a novel myocardial metabolic storage disease,
      in which hypertrophy, ventricular pre-excitation and conduction system defects
      coexist.

PMID- 11827996
TI  - Dipeptidyl peptidase I activates neutrophil-derived serine proteases and
      regulates the development of acute experimental arthritis.
AB  - Leukocyte recruitment in inflammation is critical for host defense, but excessive
      accumulation of inflammatory cells can lead to tissue damage. Neutrophil-derived
      serine proteases (cathepsin G [CG], neutrophil elastase [NE], and proteinase 3
      [PR3]) are expressed specifically in mature neutrophils and are thought to play
      an important role in inflammation. To investigate the role of these proteases in
      inflammation, we generated a mouse deficient in dipeptidyl peptidase I (DPPI) and
      established that DPPI is required for the full activation of CG, NE, and PR3.
      Although DPPI(-/-) mice have normal in vitro neutrophil chemotaxis and in vivo
      neutrophil accumulation during sterile peritonitis, they are protected against
      acute arthritis induced by passive transfer of monoclonal antibodies against type
      II collagen. Specifically, there is no accumulation of neutrophils in the joints
      of DPPI(-/-) mice. This protective effect correlates with the inactivation of
      neutrophil-derived serine proteases, since NE(-/-) x CG(-/-) mice are equally
      resistant to arthritis induction by anti-collagen antibodies. In addition,
      protease-deficient mice have decreased response to zymosan- and immune complex
      mediated inflammation in the subcutaneous air pouch. This defect is accompanied
      by a decrease in local production of TNF-alpha and IL-1 beta. These results
      implicate DPPI and polymorphonuclear neutrophil-derived serine proteases in the
      regulation of cytokine production at sites of inflammation.

PMID- 11827997
TI  - Fas receptor signaling inhibits glycogen synthase kinase 3 beta and induces
      cardiac hypertrophy following pressure overload.
AB  - Congestive heart failure is a leading cause of mortality in developed countries.
      Myocardial hypertrophy resulting from hypertension often precedes heart failure.
      Understanding the signaling underlying cardiac hypertrophy and failure is of
      major interest. Here, we identified Fas receptor activation, a classical death
      signal causing apoptosis via activation of the caspase cascade in many cell
      types, as a novel pathway mediating cardiomyocyte hypertrophy in vitro and in
      vivo. Fas activation by Fas ligand induced a hypertrophic response in cultured
      cardiomyocytes, which was dependent on the inactivation of glycogen synthase
      kinase 3 beta (GSK3 beta) by phosphorylation. In vivo, lpr (lymphoproliferative
      disease) mice lacking a functional Fas receptor demonstrated rapid-onset left
      ventricular dilatation and failure, absence of compensatory hypertrophy, and
      significantly increased mortality in response to pressure overload induction that
      was accompanied by a failure to inhibit GSK3 beta activity. In contrast, Fas
      ligand was dispensable for the development of pressure overload hypertrophy in
      vivo. In vitro, neonatal cardiomyocytes from lpr mice showed a completely
      abrogated or significantly blunted hypertrophic response after stimulation with
      Fas ligand or angiotensin II, respectively. These findings indicate that Fas
      receptor signaling inhibits GSK3 beta activity in cardiomyocytes and is required
      for compensation of pressure overload in vivo.

PMID- 11827998
TI  - Altered vascular permeability and early onset of experimental autoimmune
      encephalomyelitis in PECAM-1-deficient mice.
AB  - Platelet/endothelial cell adhesion molecule-1 (PECAM-1, CD31), a 130-kDa
      glycoprotein member of the Ig superfamily of transmembrane proteins, is expressed
      on endothelial cells, platelets, and subsets of leukocytes. It functions as a
      cell adhesion molecule as well as a scaffolding molecule capable of modulating
      cellular signaling pathways. In this study, using PECAM-1-deficient (KO) mice, as
      well as cells derived from these mice, we demonstrate that the absence of PECAM-1
      expression is associated with an early onset of clinical symptoms during
      experimental autoimmune encephalomyelitis (EAE), a mouse model for the human
      autoimmune disease multiple sclerosis. During EAE, mononuclear cell extravasation
      and infiltration of the CNS occur at earlier time points in PECAM-KO mice than in
      wild-type mice. In vitro, T lymphocyte transendothelial migration across PECAM-KO
      endothelial cells is enhanced, regardless of expression of PECAM-1 on
      transmigrating T cells. Additionally, cultured PECAM-KO endothelial cells exhibit
      prolonged permeability changes in response to histamine treatment compared with
      PECAM-1-reconstituted endothelial cells. Lastly, we demonstrate an exaggerated
      and prolonged CNS vascular permeability during the development of EAE and a delay
      in restoration of dermal vascular integrity following histamine challenge in
      PECAM-KO mice.

PMID- 11827999
TI  - Dual gene therapy with SERCA1 and Kir2.1 abbreviates excitation without
      suppressing contractility.
AB  - Heart failure is characterized by depressed contractility and delayed
      repolarization. The latter feature predisposes the failing heart to ventricular
      arrhythmias and represents a logical target for gene therapy. Unfortunately,
      unopposed correction of the delay in repolarization will decrease the time
      available for calcium cycling during each heartbeat, potentially aggravating the
      depression of contractility. Here we describe the development and application of
      a novel gene therapy strategy designed to abbreviate excitation without
      depressing contraction. The calcium ATPase SERCA1 was coexpressed with the
      potassium channel Kir2.1 in guinea pig hearts. Myocytes from the hearts had
      bigger calcium transients and shorter action potentials. In vivo, repolarization
      was abbreviated, but contractile function remained unimpaired. Dual gene therapy
      of the sort described here can be generalized to exploit opposing or synergistic
      therapeutic principles to achieve a tailored phenotype.

PMID- 11828000
TI  - Regulation of prostasin by aldosterone in the kidney.
AB  - Prostasin is a serine protease present in mammalian urine that increases the
      activity of the epithelial sodium channel (ENaC) when the two are coexpressed in
      Xenopus oocytes. To determine if aldosterone, one of the principal regulators of
      urinary Na reabsorption by the distal nephron, affects prostasin expression, we
      examined prostasin mRNA and protein in a cultured mouse cortical collecting duct
      cell line (M-1), whole rats, and patients with primary aldosteronism. Aldosterone
      treatment of M-1 cells substantially increased prostasin expression and
      stimulated (22)Na uptake. Urinary excretion of prostasin in rats that were
      infused with aldosterone likewise increased by approximately 4-fold when compared
      with the vehicle-infused rats. Finally, urinary excretion of prostasin in
      patients with primary aldosteronism was substantially increased when compared
      with normal patients. Adrenalectomy reduced urinary prostasin excretion to
      control levels, whereas urinary prostasin levels were not altered in patients
      undergoing surgery for other reasons. In patients with primary aldosteronism,
      reduction in the urinary excretion of prostasin correlated with the increase in
      the urinary Na/K ratio. These findings, together with our previous report that
      prostasin activates the amiloride-sensitive Na currents through ENaC, demonstrate
      that prostasin regulates Na balance in vivo by virtue of its heightened
      expression in the presence of aldosterone.

PMID- 11828001
TI  - Autologous dendritic cells transfected with prostate-specific antigen RNA
      stimulate CTL responses against metastatic prostate tumors.
AB  - Autologous dendritic cells (DCs) transfected with mRNA encoding prostate-specific
      antigen (PSA) are able to stimulate potent, T cell-mediated antitumor immune
      responses in vitro. A phase I trial was performed to evaluate this strategy for
      safety, feasibility, and efficacy to induce T cell responses against the self
      protein PSA in patients with metastatic prostate cancer. In 13 study subjects,
      escalating doses of PSA mRNA-transfected DCs were administered with no evidence
      of dose-limiting toxicity or adverse effects, including autoimmunity. Induction
      of PSA-specific T cell responses was consistently detected in all patients,
      suggesting in vivo bioactivity of the vaccine. Vaccination was further associated
      with a significant decrease in the log slope PSA in six of seven subjects; three
      patients that could be analyzed exhibited a transient molecular clearance of
      circulating tumor cells. The demonstration of vaccine safety, successful in vivo
      induction of PSA-specific immunity, and impact on surrogate clinical endpoints
      provides a scientific rationale for further clinical investigation of RNA
      transfected DCs in the treatment of human cancer.

PMID- 11828002
TI  - The Fas-associated death domain protein suppresses activation of NF-kappa B by
      LPS and IL-1 beta.
AB  - Activation of NF-kappa B by bacterial LPS promotes the upregulation of
      proinflammatory cytokines that contribute to the pathogenesis of Gram-negative
      septic shock. LPS activation of NF-kappa B is dependent upon the interaction of
      two death domain-containing (DD-containing) proteins, MyD88 and IL-1 receptor
      associated kinase IRAK. Another DD-containing protein, Fas-associated death
      domain (FADD), also binds MyD88 through respective DD-DD interactions. Although
      FADD has been classically described as a proapoptotic signaling molecule, several
      reports have implicated a role for FADD in mediating NF-kappa B activation. In
      the present report, we investigated whether FADD could mediate LPS activation of
      NF-kappa B. Overexpression of FADD blocked LPS-induced NF-kappa B activation,
      whereas absence of FADD enhanced activation of NF-kappa B by LPS. Further, LPS
      induced expression of two NF-kappa B-dependent gene products, IL-6 and KC, was
      enhanced in FADD(-/-) mouse embryo fibroblasts (MEFs) compared with wild-type.
      This increase in NF-kappa B activity correlated with enhanced I kappa B
      degradation. FADD(-/-) MEFs were also resistant to NF-kappa B activation induced
      by IL-1 beta. Finally, reconstitution of full-length FADD in the FADD(-/-) MEFs
      completely reversed the enhanced activation of NF-kappa B elicited by either LPS
      or IL-1 beta. Together, these data indicate that FADD negatively regulates LPS-
      and IL-1 beta-induced NF-kappa B activation and that this regulation occurs
      upstream of I kappa B degradation.

PMID- 11828003
TI  - Aging leads to disturbed homeostasis of memory phenotype CD8(+) cells.
AB  - Examining the rate of in vivo T cell turnover (proliferation) in aged mice
      revealed a marked reduction in turnover at the level of memory-phenotype CD44(hi)
      CD8(+) cells relative to young mice. Based on adoptive transfer experiments, the
      reduced turnover of aged CD44(hi) CD8(+) cells reflected an inhibitory influence
      of the aged host environment. Aged CD44(hi) CD8(+) cells also showed poor in vivo
      responses to IL-15 and IL-15-inducing agents, but responded well to IL-15 in
      vitro. Two mechanisms could account for the reduced turnover of aged CD44(hi)
      CD8(+) cells in vivo. First, aging was associated with a prominent and selective
      increase in Bcl-2 expression in CD44(hi) CD8(+) cells. Hence, the reduced
      turnover of aged CD44(hi) CD8(+) cells may in part reflect the antiproliferative
      effect of enhanced Bcl-2 expression. Second, the impaired in vivo response of
      aged CD44(hi) CD8(+) cells to IL-15 correlated with increased serum levels of
      type I interferons (IFN-I) and was largely reversed by injection of anti-IFN-I
      antibody. Hence the selective reduction in the turnover of aged CD44(hi) CD8(+)
      cells in vivo may reflect the combined inhibitory effects of enhanced Bcl-2
      expression and high IFN-I levels.

PMID- 11828005
TI  - Restrictions limiting the generation of DNA double strand breaks during
      chromosomal V(D)J recombination.
AB  - Antigen receptor loci are composed of numerous variable (V), diversity (D), and
      joining (J) gene segments, each flanked by recombination signal sequences (RSSs).
      The V(D)J recombination reaction proceeds through RSS recognition and DNA
      cleavage steps making it possible for multiple DNA double strand breaks (DSBs) to
      be introduced at a single locus. Here we use ligation-mediated PCR to analyze DNA
      cleavage intermediates in thymocytes from mice with targeted RSS mutations at the
      endogenous TCRbeta locus. We show that DNA cleavage does not occur at individual
      RSSs but rather must be coordinated between RSS pairs flanking gene segments that
      ultimately form coding joins. Coordination of the DNA cleavage step occurs over
      great distances in the chromosome and favors intra- over interchromosomal
      recombination. Furthermore, through several restrictions imposed on the
      generation of both nonpaired and paired DNA DSBs, this requirement promotes
      antigen receptor gene integrity and genomic stability in developing lymphocytes
      undergoing V(D)J recombination.

PMID- 11828004
TI  - Matrix metalloproteinases (MMPs) regulate fibrin-invasive activity via MT1-MMP
      dependent and -independent processes.
AB  - Cross-linked fibrin is deposited in tissues surrounding wounds, inflammatory
      sites, or tumors and serves not only as a supporting substratum for trafficking
      cells, but also as a structural barrier to invasion. While the plasminogen
      activator-plasminogen axis provides cells with a powerful fibrinolytic system,
      plasminogen-deleted animals use alternate proteolytic processes that allow fibrin
      invasion to proceed normally. Using fibroblasts recovered from wild-type or gene
      deleted mice, invasion of three-dimensional fibrin gels proceeded in a matrix
      metalloproteinase (MMP)-dependent fashion. Consistent with earlier studies
      supporting a singular role for the membrane-anchored MMP, MT1-MMP, in fibrin
      invasive events, fibroblasts from MT1-MMP-null mice displayed an early defect in
      invasion. However, MT1-MMP-deleted fibroblasts circumvented this early deficiency
      and exhibited compensatory fibrin-invasive activity. The MT1-MMP-independent
      process was sensitive to MMP inhibitors that target membrane-anchored MMPs, and
      further studies identified MT2-MMP and MT3-MMP, but not MT4-MMP, as alternate pro
      invasive factors. Given the widespread distribution of MT1-, 2-, and 3-MMP in
      normal and neoplastic cells, these data identify a subset of membrane-anchored
      MMPs that operate in an autonomous fashion to drive fibrin-invasive activity.

PMID- 11828006
TI  - Differential T cell function and fate in lymph node and nonlymphoid tissues.
AB  - The functions and fate of antigen-experienced T cells isolated from lymph node or
      nonlymphoid tissues were analyzed in a system involving adoptive transfer of in
      vitro-activated T cells into mice. Activated T cells present in the lymph nodes
      could be stimulated by antigen to divide, produce effector cytokines, and migrate
      to peripheral tissues. By contrast, activated T cells that had migrated into
      nonlymphoid tissues (lung and airway) produced substantial effector cytokines
      upon antigen challenge, but were completely unable to divide or migrate back to
      the lymph nodes. Therefore, activated T cells can undergo clonal expansion in the
      lymph node, but are recruited and retained as nondividing cells in nonlymphoid
      tissues. These distinct regulatory events in lymph node and nonlymphoid tissues
      reveal simple key mechanisms for both inducing and limiting T cell immunity.

PMID- 11828007
TI  - Reciprocal activating interaction between natural killer cells and dendritic
      cells.
AB  - We analyzed the interaction between human peripheral blood natural killer (NK)
      cells and monocyte-derived immature dendritic cells (DC). Fresh NK cells were
      activated, as indicated by the induced expression of the CD69 antigen, and their
      cytolytic activity was strongly augmented by contact with lipopolysaccharide
      (LPS)-treated mature DC, or with immature DC in the presence of the maturation
      stimuli LPS, Mycobacterium tuberculosis or interferon (IFN)-alpha. Reciprocally,
      fresh NK cells cultured with immature DC in the presence of the maturation
      stimuli strongly enhanced DC maturation and interleukin (IL)-12 production. IL-2-
      activated NK cells directly induced maturation of DC and enhanced their ability
      to stimulate allogeneic naive CD4(+) T cells. The effects of NK cells were cell
      contact dependent, although the secretion of IFN-gamma and TNF also contributed
      to DC maturation. Within peripheral blood lymphocytes the reciprocal activating
      interaction with DC was restricted to NK cells, because the other lymphocyte
      subsets were neither induced to express CD69, nor induced to mature in contact
      with DC. These data demonstrated for the first time a bidirectional cross talk
      between NK cells and DC, in which NK cells activated by IL-2 or by mature DC
      induce DC maturation.

PMID- 11828008
TI  - Contact-dependent stimulation and inhibition of dendritic cells by natural killer
      cells.
AB  - Natural killer (NK) cells and dendritic cells (DCs) are two distinct cell types
      of innate immunity. It is known that the in vitro interaction of human NK cells
      with autologous DCs results in DC lysis. Here we show that contact-dependent
      interactions between activated human NK cells and immature DCs (iDCs) provides a
      "control switch" for the immune system. At low NK/DC ratios, this interaction
      dramatically amplifies DC responses, whereas at high ratios it completely turns
      off their responses. Specifically, culture of activated human NK cells with iDCs,
      at low NK/DC ratios (1:5), led to exponential increases in DC cytokine
      production, which were completely dependent on cell-to-cell contact. DC
      maturation was also driven by cognate interactions with NK cells and maturation
      was dependent on endogenously produced TNF-alpha in the culture. At slightly
      higher NK/DC ratios (5:1), inhibition of DC functions was the dominant feature
      due to potent killing by the autologous NK cells. Resting NK cells also
      stimulated autologous DC maturation in a TNF-alpha/contact-dependent manner,
      however, increasing the NK/DC ratio only led to an enhancement of this effect.

PMID- 11828009
TI  - Human dendritic cells activate resting natural killer (NK) cells and are
      recognized via the NKp30 receptor by activated NK cells.
AB  - During the innate response to many inflammatory and infectious stimuli, dendritic
      cells (DCs) undergo a differentiation process termed maturation. Mature DCs
      activate antigen-specific naive T cells. Here we show that both immature and
      mature DCs activate resting human natural killer (NK) cells. Within 1 wk the NK
      cells increase two-- to fourfold in numbers, start secreting interferon (IFN)
      gamma, and acquire cytolytic activity against the classical NK target LCL721.221.
      The DC-activated NK cells then kill immature DCs efficiently, even though the
      latter express substantial levels of major histocompatibility complex (MHC) class
      I. Similar results are seen with interleukin (IL)-2--activated NK cell lines and
      clones, i.e., these NK cells kill and secrete IFN-gamma in response to immature
      DCs. Mature DCs are protected from activated NK lysis, but lysis takes place if
      the NK inhibitory signal is blocked by a human histocompatibility leukocyte
      antigen (HLA)-A,B,C--specific antibody. The NK activating signal mainly involves
      the NKp30 natural cytotoxicity receptor, and not the NKp46 or NKp44 receptor.
      However, both immature and mature DCs seem to use a NKp30 independent mechanism
      to act as potent stimulators for resting NK cells. We suggest that DCs are able
      to control directly the expansion of NK cells and that the lysis of immature DCs
      can regulate the afferent limb of innate and adaptive immunity.

PMID- 11828010
TI  - +1 Frameshifting as a novel mechanism to generate a cryptic cytotoxic T
      lymphocyte epitope derived from human interleukin 10.
AB  - Recent data indicate that some cytotoxic T cells (CTLs) recognize so-called
      cryptic epitopes, encoded by nonprimary open reading frame (ORF) sequences or
      other nonclassical expression pathways. We describe here a novel mechanism
      leading to generation of a cryptic CTL epitope. We isolated from the synovial
      fluid of a patient suffering from a Reiter's syndrome an autoreactive T cell
      clone that recognized cellular IL-10 in the HLA-B*2705 context. The minimal IL-10
      sequence corresponding to nucleotides 379-408 was shown to activate this clone,
      upon cotransfection into COS cells with the DNA encoding HLA-B*2705, but the
      synthetic peptide deduced from this sequence did not stimulate the clone. Using a
      site-directed mutagenesis approach, we found that this clone recognized a
      transframe epitope generated by an internal +1 frameshifting in the IL-10
      sequence and so derived partly from ORF1, partly from ORF2. We defined that +1
      frameshifting was induced by a specific heptamer sequence. These observations
      illustrate the variety of mechanisms leading to generation of cryptic epitopes
      and suggest that frameshifting in normal cellular genes may be more common than
      expected.

PMID- 11828011
TI  - The immune response to pneumococcal proteins during experimental human carriage.
AB  - Colonization of the nasopharynx is the initial step in all infections caused by
      Streptococcus pneumoniae. The antibody response to carriage was examined in an
      experimental model of human colonization in healthy adults. Asymptomatic
      colonization was detected in 6/14 subjects and continued for up to 122 d.
      Susceptibility to carriage did not correlate with total serum immunoglobulin
      (Ig)G to the homotypic capsular polysaccharide. All of the colonized subjects, in
      contrast, developed a serum IgG and secretory IgA response to a 22 kD protein,
      whereas 7 of 8 subjects who did not become colonized had preexisting antibody to
      this protein. Analysis of the 22 kD protein identified it as the NH(2)-terminal
      region of pneumococcal surface protein A (PspA). Our findings provide evidence
      for the role of antibody to this protein fragment in preventing pneumococcal
      carriage by humans.

PMID- 11828013
TI  - Evidence for a role of mast cells in the evolution to congestive heart failure.
AB  - Mast cells are believed to be involved in the pathophysiology of heart failure,
      but their precise role in the process is unknown. This study examined the role of
      mast cells in the progression of heart failure, using mast cell-deficient (WBB6F1
      W/W(v)) mice and their congenic controls (wild-type [WT] mice). Systolic pressure
      overload was produced by banding of the abdominal aorta, and cardiac function was
      monitored over 15 wk. At 4 wk after aortic constriction, cardiac hypertrophy with
      preserved left ventricular performance (compensated hypertrophy) was observed in
      both W/W(v) and WT mice. Thereafter, left ventricular performance gradually
      decreased in WT mice, and pulmonary congestion became apparent at 15 wk
      (decompensated hypertrophy). In contrast, decompensation of cardiac function did
      not occur in W/W(v) mice; left ventricular performance was preserved throughout,
      and pulmonary congestion was not observed. Perivascular fibrosis and upregulation
      of mast cell chymase were all less apparent in W/W(v) mice. Treatment with
      tranilast, a mast cell-stabilizing agent, also prevented the evolution from
      compensated hypertrophy to heart failure. These observations suggest that mast
      cells play a critical role in the progression of heart failure. Stabilization of
      mast cells may represent a new approach in the management of heart failure.

PMID- 11828014
TI  - Low-level hypermutation in T cell-independent germinal centers compared with high
      mutation rates associated with T cell-dependent germinal centers.
AB  - Exceptionally germinal center formation can be induced without T cell help by
      polysaccharide-based antigens, but these germinal centers involute by massive B
      cell apoptosis at the time centrocyte selection starts. This study investigates
      whether B cells in germinal centers induced by the T cell-independent antigen (4
      hydroxy-3-nitrophenyl)acetyl (NP) conjugated to Ficoll undergo hypermutation in
      their immunoglobulin V region genes. Positive controls are provided by comparing
      germinal centers at the same stage of development in carrier-primed mice
      immunized with a T cell-dependent antigen: NP protein conjugate. False positive
      results from background germinal centers and false negatives from non-B cells in
      germinal centers were avoided by transferring B cells with a transgenic B cell
      receptor into congenic controls not carrying the transgene. By 4 d after
      immunization, hypermutation was well advanced in the T cell-dependent germinal
      centers. By contrast, the mutation rate for T cell-independent germinal centers
      was low, but significantly higher than in NP-specific B cells from nonimmunized
      transgenic mice. Interestingly, a similar rate of mutation was seen in
      extrafollicular plasma cells at this stage. It is concluded that efficient
      activation of hypermutation depends on interaction with T cells, but some
      hypermutation may be induced without such signals, even outside germinal centers.

PMID- 11828012
TI  - Role for mismatch repair proteins Msh2, Mlh1, and Pms2 in immunoglobulin class
      switching shown by sequence analysis of recombination junctions.
AB  - B cells from mice deficient in mismatch repair (MMR) proteins show decreased
      ability to undergo class switch recombination in vitro and in vivo. The deficit
      is not accompanied by any reduction in cell viability or alterations in the cell
      cycle in B cells cultured in vitro. To assess the role of MMR in switching we
      examined the nucleotide sequences of Smicro-Sgamma3 recombination junctions in
      splenic B cells induced in culture to switch to IgG3. The data demonstrate clear
      differences in the sequences of switch junctions in wild-type B cells in
      comparison with Msh2-, Mlh1-, and Pms2-deficient B cells. Sequences of switch
      junctions from Msh2-deficient cells showed decreased lengths of microhomology
      between Smicro and Sgamma3 relative to junctions from wild-type cells and an
      increase in insertions, i.e., nucleotides which do not appear to be derived from
      either the Smicro or Sgamma3 parental sequence. By contrast, 23% of junctions
      from Mlh1- and Pms2-deficient cells occurred at unusually long stretches of
      microhomology. The data indicate that MMR proteins are directly involved in class
      switching and that the role of Msh2 differs from that of Mlh1 and Pms2.

PMID- 11828015
TI  - Dendritic and natural killer cells cooperate in the control/switch of innate
      immunity.

PMID- 11828016
TI  - Ped3p is a peroxisomal ATP-binding cassette transporter that might supply
      substrates for fatty acid beta-oxidation.
AB  - Glyoxysomes, a group of specialized peroxisomes, are organelles that degrade
      fatty acids by the combination of fatty acid beta-oxidation and glyoxylate cycle.
      However, the mechanism underlying the transport of the fatty acids across the
      peroxisomal membrane is still obscure in higher plant cells. We identified and
      analyzed the PED3 gene and its gene product, Ped3p. The phenotype of the
      Arabidopsis ped3 mutant indicated that the mutation in the PED3 gene inhibits the
      activity of fatty acid beta-oxidation. Ped3p is a 149-kDa protein that exists in
      peroxisomal membranes. The amino acid sequence of Ped3p had a typical
      characteristic for "full-size" ATP-binding cassette (ABC) transporter consisting
      of two transmembrane regions and two ATP-binding regions. This protein was
      divided into two parts, that had 32% identical amino acid sequences. Each part
      showed a significant sequence similarity with peroxisomal "half" ABC transporters
      so far identified in mammals and yeast. Ped3p may contribute to the transport of
      fatty acids and their derivatives across the peroxisomal membrane.

PMID- 11828017
TI  - The possible involvement of a phosphate-induced transcription factor encoded by
      phi-2 gene from tobacco in ABA-signaling pathways.
AB  - A novel phosphate-induced gene, phi-2, has been identified by its induction on
      addition of phosphate to phosphate-starved tobacco BY-2 cells. The predicted gene
      product of phi-2 has significant homology to a group of bZIP proteins involved in
      ABA-signaling pathways, and phi-2 also responded to ABA treatment. A previously
      isolated phosphate-induced gene, phi-1, (Sano et al. (1999) Plant Cell Physiol.
      40: 1) was also responsive to ABA. Although phosphate addition induced semi
      synchronous cell division in phosphate-starved tobacco BY-2 cells, ABA adversely
      affected cell division. Detailed examination revealed that the high levels of
      phosphate required to induce semi-synchronous cell division seemed to be
      perceived as indicators of stress by the cells. One of the stress indicators
      perceived by the cells is a cytoplasmic pH change, to which phi-2 and phi-1 genes
      respond. The different components of the cell's response to phosphate induction
      are discussed.

PMID- 11828018
TI  - Action of xyloglucan hydrolase within the native cell wall architecture and its
      effect on cell wall extensibility in azuki bean epicotyls.
AB  - Xyloglucan hydrolase (XGH) has recently been purified from the cell wall of azuki
      bean (Vigna angularis Ohwi et Ohashi) epicotyls as a new type of xyloglucan
      degrading enzyme [Tabuchi et al. (2001) Plant Cell Physiol. 42: 154]. In the
      present study, the effects of XGH on the mechanical properties of the cell wall
      and on the level and the molecular size of xyloglucans within the native wall
      architecture were examined in azuki bean epicotyls. When the epidermal tissue
      strips from the growing regions of azuki bean epicotyls were incubated with XGH,
      the mechanical extensibility of the cell wall dramatically increased. XGH
      exogenously applied to cell wall materials (homogenates) or epidermal tissue
      strips decreased the amount of xyloglucans via the solubilization of the
      polysaccharides. Also, XGH substantially decreased the molecular mass of
      xyloglucans in both materials. These results indicate that XGH is capable of
      hydrolyzing xyloglucans within the native cell wall architecture and thereby
      increasing the cell wall extensibility in azuki bean epicotyls.

PMID- 11828019
TI  - GA(3)-induced expression of a new functional AAA-ATPase (FsA1) is correlated with
      the onset of germination in Fagus sylvatica L. seeds (beechnuts).
AB  - A full-length cDNA clone, named FsA1, has been isolated from a cDNA library
      constructed using mRNA from Fagus sylvatica L. dormant seeds (beechnuts). This
      clone shows high identity with members of the AAA superfamily, for ATPases
      Associated with a variety of cellular Activities, encoding subunit 8 of the 26S
      proteasome or Tat binding proteins (TBPs). Direct biochemical evidence supporting
      Mg(2+)-dependent ATPase activity has been obtained by expressing FsA1 in
      Escherichia coli as histidine tag fusion protein and using the recombinant
      protein in the stimulation of ATP hydrolysis. Analysis of the expression of FsA1
      transcripts during stratification shows an increase in the presence of
      gibberellic acid (GA(3)), a treatment that proved to be efficient in breaking
      dormancy and increasing germination percentages of these seeds, while the
      addition of paclobutrazol, a well-known GA biosynthesis inhibitor, greatly
      reduces the expression of the clone. A low level of expression was maintained in
      the stratification control in H(2)O, where dormancy is slowly released. These
      results show that this new member of the AAA-ATPase family is up-regulated by GAs
      and its expression correlated with the germination arise in Fagus sylvatica
      seeds. The possible function of this protein during the transition from dormancy
      to germination is discussed.

PMID- 11828020
TI  - Phototropism and gravitropism in lateral roots of Arabidopsis.
AB  - Gravitropism and, to a lesser extent, phototropism have been characterized in
      primary roots, but little is known about structural/functional aspects of these
      tropisms in lateral roots. Therefore, in this study, we report on tropistic
      responses in lateral roots of Arabidopsis thaliana. Lateral roots initially are
      plagiogravitropic, but when they reach a length of approximately 10 mm, these
      roots grow downward and exhibit positive orthogravitropism. Light and electron
      microscopic studies demonstrate a correlation between positive gravitropism and
      development of columella cells with large, sedimented amyloplasts in wild-type
      plants. Lateral roots display negative phototropism in response to white and blue
      light and positive phototropism in response to red light. As is the case with
      primary roots, the photoresponse is weak relative to the graviresponse, but
      phototropism is readily apparent in starchless mutant plants, which are impaired
      in gravitropism. To our knowledge, this is the first report of phototropism of
      lateral roots in any plant species.

PMID- 11828021
TI  - A loss-of-function mutation in the rice KNOX type homeobox gene, OSH3.
AB  - KNOX homeodomain (HD) proteins encoded by KNOTTED1-like homeobox genes (KNOX
      genes) are thought to work as switches for cells to change from an indeterminate
      to a determinate state, although their direct functions are not clear. In the
      process of isolating KNOX genes from rice, we found that one gene, named OSH3,
      has two amino acid substitutions in three of the invariant amino acid residues in
      the HD of KNOX proteins. These amino acid substitutions are not universal in
      rice: two of the cultivars from the Indica variety of rice do not carry those
      substitutions but two of the cultivars from Japonica variety do. We tested the
      effect of these amino acid substitutions on their ability to form dimers and to
      induce abnormal morophologies when overexpressed in transgenic plants. We found
      that OSH3 without those substitutions can form dimers and can induce an abnormal
      phenotype in overexpression studies, and that OSH3 with those amino acid
      substitutions is defective in both. Based on these observations, we concluded
      that OSH3 from two of the cultivars from the Japonica variety could have lost its
      original function, or could have acquired a novel function by modifying the
      action of HD, or both.

PMID- 11828022
TI  - Ectopic expression of SUPERMAN suppresses development of petals and stamens.
AB  - The floral regulatory gene SUPERMAN (SUP) encodes a C2H2 type zinc finger protein
      that is required for maintaining boundaries between floral organs in Arabidopsis.
      It has been proposed that the main function of SUP is to balance cell
      proliferation in the third and fourth whorl of developing flowers, thereby
      maintaining the boundaries between the two whorls. To gain further insight into
      the function of SUP, we have ectopically expressed SUP using the promoter of
      APETALA1 (AP1), a gene that is initially expressed throughout floral meristems
      and later becomes restricted to the first and second whorls. Flowers of AP1::SUP
      plants have fewer floral organs, consistent with an effect of SUP on cell
      proliferation. In addition, the AP1::SUP transgene caused the conversion of
      petals to sepals and suppressed the development of stamens. The expression of the
      B function homeotic gene APETALA3 (AP3) and its regulator UNUSUAL FLORAL ORGANS
      (UFO) were delayed and reduced in AP1::SUP flowers. However, SUP does not act
      merely through UFO, as constitutive expression of UFO did not rescue the defects
      in petal and stamen development in AP1::SUP flowers. Together, these results
      suggest that SUP has both indirect and direct effects on the expression of B
      function homeotic genes.

PMID- 11828023
TI  - The APRR1/TOC1 quintet implicated in circadian rhythms of Arabidopsis thaliana:
      I. Characterization with APRR1-overexpressing plants.
AB  - Several Arabidopsis genes have been proposed to encode potential clock-associated
      components, including the Myb-related CCA1 and LHY transcription factors and a
      member of the novel family of pseudo response regulators (APRR1/TOC1). We
      previously showed that mRNAs of the APRR1/TOC1 family of genes start accumulating
      after dawn rhythmically and sequentially at approximately 2 h intervals in the
      order: APRR9--> APRR7-->APRR5-->APRR3-->APRR1/TOC1. Here we constructed APRR1
      overexpressing (APRR1-ox) plants, and examined certain circadian profiles for
      APRRs, CCA1, LHY, GI, CCR2, and CAB2. The free-running circadian rhythms of the
      APRR1/TOC1 family of genes, including APRR1, were dampened in APRR1-ox plants. In
      particular, the light-inducible expression of APRR9 was severely repressed in
      APRR1-ox plants, suggesting that there is a negative APRR1-->APRR9 regulation.
      The free-running robust rhythm of CAB2 was also dampened in APRR1-ox. The
      circadian profiles of potential clock-associated genes, CCA1, LHY, GI, and CCR2
      were all markedly altered in APRR1-ox, each in characteristic fashion. To gain
      further insight into the molecular function of APRR1, we then identified a novel
      Myc-related bHLH transcription factor, which physically associated with APRR1.
      This protein (named PIL1) is similar in its amino acid sequence to PIF3, which
      has been identified as a phytochrome-interacting transcription factor. These
      results are discussed in relation to the current idea that APRR1 (TOC1) plays a
      role within, or close to, the Arabidopsis central oscillator.

PMID- 11828024
TI  - Effects of HgCl(2) on CO(2) dependence of leaf photosynthesis: evidence
      indicating involvement of aquaporins in CO(2) diffusion across the plasma
      membrane.
AB  - Experiments were conducted to examine whether mercury-sensitive aquaporins
      facilitate photosynthetic CO(2) diffusion across the plasma membrane of leaf
      mesophyll cells. Discs without abaxial epidermes from Vicia faba leaflets were
      treated with HgCl(2), an inhibitor of aquaporins. Hydraulic conductivity of the
      plasma membrane of these discs, measured as the weight loss of the discs in the 1
      M sorbitol solution, was inhibited by sub-mM concentrations of HgCl(2) by 70 to
      80%. Photosynthetic CO(2) fixation was also inhibited by the HgCl(2) treatment in
      a similar concentration range. When 0.3 mM HgCl(2) solution was fed to the V.
      faba leaflets with intact epidermes via the transpiration stream, the rate of
      photosynthesis on leaf area basis (A) measured at photosynthetically active
      photon flux density of 700 micromol m(-2) s(-1) and at leaf temperature of 25
      degrees C, decreased by about 20 to 30% at any CO(2) concentration in the
      intercellular spaces (C(i)). However, when CO(2) concentration in the chloroplast
      stroma (C(c)) was calculated from fluorescence and gas exchange data and A was
      plotted against C(c), A at low C(c) concentrations did not differ before and
      after the treatment. The conductance for CO(2) diffusion from the intercellular
      spaces to the chloroplast stroma (g(i)) decreased to 40 and 30% of the control
      value, when the leaflets were fed with 0.3 mM and 1.2 mM HgCl(2), respectively.
      Similar results were obtained with leaves of Phaseolus vulgaris. Although effects
      of HgCl(2) were not specific, the present results showed that HgCl(2)
      consistently lowered g(i). It is, thus, probable that the photosynthetic CO(2)
      uptake across the plasma membrane of the mesophyll cells is facilitated by
      mercury-sensitive aquaporins.

PMID- 11828025
TI  - Analysis of early processes in wound-induced vascular regeneration using TED3 and
      ZeHB3 as molecular markers.
AB  - Interruption of the vascular bundles of Zinnia internodes induced
      transdifferentiation of cells into tracheary elements (TEs) or sieve elements
      (SEs) within 4 d of wounding. The early stage of the regeneration processes was
      analyzed using two molecular marker genes, TED3 and ZeHB3, which are expressed
      specifically in TE precursor cells and immature phloem cells, respectively. An
      increase in the numbers of TED3 and ZeHB3 mRNA-expressing cells always preceded
      an increase in the numbers of TEs and SEs formed. The earliest sign of vascular
      differentiation was the appearance 24 h after wounding of a layer(s) of TED3 mRNA
      expressing cells in the inter- and intrafascicular cambial-like regions along the
      severed vascular bundles. In contrast, the number of ZeHB3 mRNA-expressing cells
      decreased dramatically along the severed bundles 24 h after wounding, and
      increased again 36 h after wounding. These results clearly indicate that xylem
      and phloem differentiation are not synchronized during vascular regeneration.
      Treatment with 10(-3) M colchicine abolished the expression of ZeHB3 mRNA in pith
      parenchyma, but not TED3 mRNA; this suggests that cell division is a prerequisite
      for the transdifferentiation of pith parenchymal cells into immature phloem cells
      expressing ZeHB3. In contrast, transdifferentiation of pith parenchymal cells to
      TE precursor cells does not require preceding cell division. However, the
      inhibition of cell division prevented the formation of both radial files of TEs
      and the cambial-like layer(s) of TED3 mRNA-expressing cells, and, ultimately,
      vascular regeneration altogether. These results imply that wound-induced cambial
      like activity in and between severed vascular bundles is essential for vascular
      regeneration.

PMID- 11828026
TI  - A pharmacological approach to test the diffusible signal activity of reactive
      oxygen intermediates in elicitor-treated tobacco leaves.
AB  - The capacity of H(2)O(2), the most stable of the reactive oxygen species (ROI),
      to diffuse freely across biological membranes and to signal gene expression
      suggests that H(2)O(2) could function as a short-lived second messenger diffusing
      from cell to cell. We tested this hypothesis in tobacco plants treated with a
      glycoprotein elicitor. Applied at 50 nM, it induces H(2)O(2) accumulation and the
      hypersensitive response restricted to the infiltrated zone 1 tissue. Stimulation
      of a set of defense responses also occurs in the surrounding zone 2 tissue
      without diffusion of the elicitor. ROI levels in zone 1 were modulated using N
      acetyl-L-cysteine (NAC) as a ROI scavenger and Rose Bengal (RB) as a ROI
      generator. We found that ROI appeared to act as signalling intermediates in
      pathways leading to salicylic acid accumulation, to PR1, PR5 and 3-hydroxy-3
      methylglutarylCoA reductase expression in glycoprotein-treated zone 1 tissues.
      Compared to the treatment with the elicitor alone, co-infiltration of the
      glycoprotein and NAC increased the surface of zone 2 showing PR1 and O
      methyltransferase expression. Application of RB had the opposite effect. The data
      suggest that, in our system, ROI did not act as a cell-to-cell diffusible signal
      to activate PR protein and O-methyltransferase expression in zone 2.

PMID- 11828027
TI  - Arabidopsis GARP transcriptional activators interact with the Pro-rich activation
      domain shared by G-box-binding bZIP factors.
AB  - The Pro-rich regions, found in a subset of plant bZIP transcription factors,
      including G-box-binding factors (GBFs) of Arabidopsis thaliana, are thought to be
      deeply involved in transcriptional regulation. However, the molecular mechanisms
      of the Pro-rich region-mediated transcriptional regulation are still largely
      unknown. Here we report evidence showing that two closely related Arabidopsis
      proteins, designated GPRI1 and GPRI2, containing a GARP DNA-binding domain, are
      likely partners of one or more GBFs. The results of yeast two-hybrid assays and
      in vitro binding assays indicated that GPRI1 can interact with the Pro-rich
      regions of GBF1 and GBF3. GPRI2 interacted with the Pro-rich region of GBF1.
      GPRI1 and GPRI2 transactivated transcription in yeast. In GPRI1 the region
      responsible for this activation was mapped in the N-terminal third of the
      protein. Transient assays showed that in Arabidopsis cells not only the N
      terminal but also the C-terminal regions of GPRI1 can function as a separable
      activation domain. GPRI1 and GPRI2 may function in some promoters in concert with
      a GBF through interaction with its Pro-rich region to enhance the transcriptional
      level of the corresponding genes.

PMID- 11828029
TI  - The APRR1/TOC1 quintet implicated in circadian rhythms of Arabidopsis thaliana:
      II. Characterization with CCA1-overexpressing plants.
AB  - We previously identified a novel class of proteins, named pseudo-response
      regulators (APRRs) in Arabidopsis thaliana, each of which (APRR1, APRR3, APRR5,
      APRR7, and APRR9) has an intriguing structural design containing an N-terminal
      pseudo receiver domain and a C-terminal CONSTANS motif. Among them, APRR1 is
      identical to TOC1, previously proposed to be a candidate component of an
      Arabidopsis circadian clock. Intriguingly, expressions of the APRR1/TOC1 family
      of genes are under control of coordinate circadian rhythms at the level of
      transcription, in the manner that each APRR-transcript starts accumulating
      sequentially after dawn with 2 to 3 h intervals in the order: APRR9-->APRR7-
      >APRR5-->APRR3-->APRR1/TOC1. Here we examined this circadian-related event,
      "circadian waves of the APRR1/TOC1 quintet", by employing CCA1-overexpression
      (CCA1-ox) transgenic plants, based on the fact that CCA1 is a well-characterized
      and the most plausible oscillator component. It was found that aberrant
      overexpression of the CCA1 gene severely perturbed free-running and sequential
      rhythms of the APRR1/TOC1 family of genes. In the accompanying paper, it was
      shown that overexpression of APRR1 also results in a marked alteration of the
      CCA1 circadian rhythm, and vice versa. Taken together, it was suggested that
      there are intimate and mutual links between these two types of circadian
      associated components (APRRs and CCA1).

PMID- 11828028
TI  - A wound-inducible tobacco peroxidase gene expresses preferentially in the
      vascular system.
AB  - A tobacco peroxidase gene tpoxN1 was reported to be expressed within 1 h after
      wounding in leaves [Hiraga et al. (2000a) Plant Cell Physiol. 41: 165]. We
      describe here further results on the wound-induced tpoxN1 expression. The quick
      tpoxN1 induction occurred preferentially in stems and petioles, but was
      negligible in leaf blades even 8 h after wounding. Induced GUS activity was also
      detected rapidly after wounding in the stem of transgenic tobacco plants carrying
      the tpoxN1 promoter::GUS fusion gene, localized mainly in the vascular systems
      where it was maintained this level for 14 d or more. Strong GUS activity was also
      found in the petiole and veinlet as well as the epidermal tissue in the stem.
      Treatment of known inducers for wound-responsive genes such as jasmonate, 1
      aminocyclopropane-1-carboxylate, spermine, phytohormones and other stress
      treatments did not enhance wound-induced tpoxN1 gene expression in stems at all,
      but rather repressed it in some cases. Studies using metabolic inhibitors
      suggested that phosphorylation and dephosphorylation of proteins together with de
      novo protein synthesis are likely to be involved in the wound-induced tpoxN1
      expression as well as some other wound-responsive genes. Thus, tpoxN1 is a unique
      wound-inducible and possible wound-healing gene which is rapidly expressed being
      maintained for a long time in veins via an unknown wound-signaling pathway(s).

PMID- 11828030
TI  - An Arabidopsis histidine-containing phosphotransfer (HPt) factor implicated in
      phosphorelay signal transduction: overexpression of AHP2 in plants results in
      hypersensitiveness to cytokinin.
AB  - Histidine-containing phosphotransfer (HPt) factors from Arabidopsis thaliana,
      designated as AHPs, function most likely in concert with histidine (His)-kinases
      (HKs) and response regulators (RRs) in certain multistep histidine (His)-
      >aspartate (Asp) phosphorelays that are involved in the signal transduction
      mechanisms, by which plant cells appear to respond to certain hormonal stimuli,
      including cytokinin. Although some previous in vitro results from studies on
      Arabidopsis AHPs (AHP1 to AHP5) supported this hypothesis, it has not yet been
      proven. To this end, here we constructed transgenic plants that contained the
      AHP2 protein in a considerably higher amount than in wild-type plants. Such AHP2
      overexpressing young seedlings were examined in comparison with wild-type plants,
      with special reference to hormone responses; particularly, their inhibitory
      effects on root elongation of plants grown on agar-plates, and also hypocotyl
      elongation of etiolated seedlings grown in the dark. The results of this study
      suggested that AHP2-overexpressing plants showed a characteristic phenotype of
      cytokinin-hypersensitive. These in vivo observations were best interpreted by
      assuming that the AHP factor(s) is somehow implicated, if not directly, in a
      cytokinin-mediated His-->Asp phosphorelay signaling in Arabidopsis.

PMID- 11828031
TI  - Ectopic expression of OsMADS3, a rice ortholog of AGAMOUS, caused a homeotic
      transformation of lodicules to stamens in transgenic rice plants.
AB  - In order to clarify the evolutionary relationship of floral organs between
      grasses and dicots, we expressed OsMADS3, a rice (Oryza sativa L.) AGAMOUS(AG)
      ortholog, in rice plants under the control of an Actin1 promoter. As a
      consequence of the ectopic expression of the OsMADS3, lodicules were homeotically
      transformed into stamens. In total, the transformation of lodicules to staminoid
      organs was observed in 18 out of 26 independent transgenic lines. In contrast to
      the almost complete transformation occurring in lodicules, none of the transgenic
      plants exhibited any morphological alterations in the palea or the lemma. Our
      results confirmed the prediction that the lodicule is an equivalent of a dicot
      petal and that the ABC model can be applied to rice at least for organ
      specification in lodicules and stamens.

PMID- 11828034
TI  - Endoscopic ultrasound: a useful tool to assess the mediastinum in patients with
      lung cancer?

PMID- 11828032
TI  - Experimentally determined sequence requirement of ACGT-containing abscisic acid
      response element.
AB  - The sequence requirement of the ACGT-containing abscisic acid response element
      (ABRE) was analyzed by systematically substituting the bases surrounding the ACGT
      core of motif A, the principal ABRE of the rice gene, OSEM: This was done within
      the context of a 55-bp promoter fragment that minimally confers ABA
      responsiveness to a heterologous promoter. Based on this analysis, the sequence
      requirement of the ACGT-containing ABRE was determined as ACGTG G/T C, which
      matched very well with the consensus derived from sequence comparison of ABA
      responsive promoters.

PMID- 11828035
TI  - Asthma in the transition from childhood to adulthood.

PMID- 11828036
TI  - Endoscopic ultrasound guided biopsy of mediastinal lesions has a major impact on
      patient management.
AB  - BACKGROUND: A study was undertaken to evaluate the clinical impact of endoscopic
      ultrasound guided fine needle aspiration biopsy (EUS-FNA) in patients with
      mediastinal masses suspected of malignancy. METHODS: From April 1993 to December
      1999, 84 patients were referred for EUS-FNA. In all patients CT scanning had
      shown a lesion of the mediastinum suspected of malignancy located adjacent to the
      oesophagus. In order to evaluate the clinical impact of EUS-FNA, the history of
      each patient up to referral for EUS-FNA was reviewed. A board of thoracic
      specialists was asked to decide the further course of the patient if EUS-FNA had
      not been available, and this diagnostic strategy was compared with the actual
      clinical course after EUS-FNA. RESULTS: For the 79 patients in whom sufficient
      verification was obtained, EUS-FNA had a sensitivity of 92%, specificity of 100%,
      PPV of 100%, NPV of 80%, and an accuracy of 94% for cancer of the mediastinum. In
      18 of 37 patients (49%) a thoracotomy/thoracoscopy was avoided as a result of EUS
      FNA, and in 28 of 41 patients (68%) a mediastinoscopy was avoided. The direct
      result of the cytological diagnosis obtained by EUS-FNA was that a final
      diagnosis of small cell lung cancer was made in eight patients resulting in
      referral for chemotherapy, and in another three patients with benign disease
      specific treatment could be initiated (sarcoidosis, mediastinal abscess, and
      leiomyoma of the oesophagus). CONCLUSIONS: EUS-FNA is a safe and sensitive
      minimally invasive method for evaluating patients with a solid lesion of the
      mediastinum suspected by CT scanning. EUS-FNA has a significant impact on patient
      management and should be considered for diagnosing the spread of cancer to the
      mediastinum in patients with lung cancer considered for surgery, as well as for
      the primary diagnosis of solid lesions located in the mediastinum adjacent to the
      oesophagus.

PMID- 11828037
TI  - Risk factors for onset and remission of atopy, wheeze, and airway
      hyperresponsiveness.
AB  - BACKGROUND: Although many children with asthma may have a remission as they grow
      and other children who did not have asthma may develop asthma in adult life,
      knowledge about the factors that influence the onset and prognosis of asthma
      during adolescence and young adulthood is very limited. METHODS: A cohort of 8-10
      year old children (n=718) living in Belmont, New South Wales, Australia were
      surveyed six times at 2 yearly intervals from 1982 to 1992, and then again 5
      years later in 1997. From this cohort, 498 subjects had between three and seven
      assessments and were included in the analysis. Atopy, airway hyperresponsiveness
      (AHR), and wheeze in the last 12 months were measured at each survey. Late onset,
      remission, and persistence were defined based on characteristics at the initial
      survey and the changes in characteristics at the follow up surveys. RESULTS: The
      proportion of subjects with late onset atopy (13.7%) and wheeze (12.4%) was
      greater than the proportion with remission of atopy (3.2%) and wheeze (5.6%).
      Having atopy at age 8-12 years (OR 2.8, 95% CI 1.5 to 5.1) and having a parental
      history of asthma (OR 2.0, 95% CI 1.02 to 4.13) were significant risk factors for
      the onset of wheeze. Having AHR at age 8-12 years was a significant risk factor
      for the persistence of wheeze (OR 4.3, 95% CI 1.3 to 15.0). Female sex (OR 1.9,
      95% CI 1.01 to 3.60) was a significant risk factor for late onset AHR whereas
      male sex (OR 1.9, 95% CI 1.1 to 2.8) was a significant risk factor for late onset
      atopy. CONCLUSIONS: The onset of AHR is uncommon during adolescence, but the risk
      of acquiring atopy and recent wheeze for the first time continues during this
      period. Atopy, particularly present at the age of 8-10 years, predicts the
      subsequent onset of wheeze.

PMID- 11828038
TI  - Sahaja yoga in the management of moderate to severe asthma: a randomised
      controlled trial.
AB  - BACKGROUND: Sahaja Yoga is a traditional system of meditation based on yogic
      principles which may be used for therapeutic purposes. A study was undertaken to
      assess the effectiveness of this therapy as an adjunctive tool in the management
      of asthma in adult patients who remained symptomatic on moderate to high doses of
      inhaled steroids. METHODS: A parallel group, double blind, randomised controlled
      trial was conducted. Subjects were randomly allocated to Sahaja yoga and control
      intervention groups. Both the yoga and the control interventions required the
      subjects to attend a 2 hour session once a week for 4 months. Asthma related
      quality of life (AQLQ, range 0-4), Profile of Mood States (POMS), level of airway
      hyperresponsiveness to methacholine (AHR), and a diary card based combined asthma
      score (CAS, range 0-12) reflecting symptoms, bronchodilator usage, and peak
      expiratory flow rates were measured at the end of the treatment period and again
      2 months later. RESULTS: Twenty one of 30 subjects randomised to the yoga
      intervention and 26 of 29 subjects randomised to the control group were available
      for assessment at the end of treatment. The improvement in AHR at the end of
      treatment was 1.5 doubling doses (95% confidence interval (CI) 0.0 to 2.9,
      p=0.047) greater in the yoga intervention group than in the control group.
      Differences in AQLQ score (0.41, 95% CI -0.04 to 0.86) and CAS (0.9, 95% CI -0.9
      to 2.7) were not significant (p>0.05). The AQLQ mood subscale did improve more in
      the yoga group than in the control group (difference 0.63, 95% CI 0.06 to 1.20),
      as did the summary POMS score (difference 18.4, 95% CI 0.2 to 36.5, p=0.05).
      There were no significant differences between the two groups at the 2 month
      follow up assessment. CONCLUSIONS: This randomised controlled trial has shown
      that the practice of Sahaja yoga does have limited beneficial effects on some
      objective and subjective measures of the impact of asthma. Further work is
      required to understand the mechanism underlying the observed effects and to
      establish whether elements of this intervention may be clinically valuable in
      patients with severe asthma.

PMID- 11828039
TI  - A novel hypothesis to explain the bronchconstrictor effect of deep inspiration in
      asthma.
AB  - BACKGROUND: In healthy subjects deep inspiration transiently dilates the airways,
      while many asthmatic subjects show bronchoconstriction by a mechanism which is
      incompletely understood. We hypothesised that the negative intrathoracic pressure
      associated with deep inspiration occurring in the context of increased leakiness
      of the airway vasculature may temporarily increase airway oedema and thus reduce
      luminal diameter in subjects with asthma. METHODS: The effects of non-forced deep
      inspiration and forced deep inspiration through resistance (generating enhanced
      negative intrathoracic pressure) on specific airway conductance (sGaw) were
      compared in 10 asthmatic and 11 healthy subjects. Each performed two respiratory
      manoeuvres: (1) sGaw was measured immediately after three deep inspirations
      without added resistance, each performed at a predetermined rate (equal to that
      when performed maximally through resistance); and (2) sGaw was measured
      immediately after three forced inspirations through resistance. RESULTS: Compared
      with deep inspiration without added resistance, sGaw was significantly reduced
      after deep inspiration through resistance in the asthmatic group by a mean (SD)
      of -13.5 (11.0)% (p=0.003) but was unchanged in the control group (-0.5 (12.4)%,
      p=0.67). CONCLUSIONS: Given the similar time-volume relationship in the two
      manoeuvres, the reduction in sGaw is unlikely to be due to differences in smooth
      muscle behaviour. It is suggested that the enhanced negative intrathoracic
      pressure acting across the airway capillaries increases airway wall oedema and
      reduces airway calibre. Such a mechanism operational during normal rapid deep
      inspiration might contribute to bronchoconstriction after deep inspiration in
      subjects with asthma.

PMID- 11828040
TI  - In search of childhood asthma: questionnaire, tests of bronchial
      hyperresponsiveness, and clinical evaluation.
AB  - BACKGROUND: The definition or diagnosis of asthma is a challenge for both
      clinicians and epidemiologists. Symptom history is usually supplemented with
      tests of bronchial hyperresponsiveness (BHR) in spite of their uncertainty in
      improving diagnostic accuracy. METHODS: To assess the interrelationship between
      respiratory symptoms, BHR, and clinical diagnosis of asthma, the respiratory
      symptoms of 1633 schoolchildren were screened using a questionnaire (response
      rate 81.2%) and a clinical study was conducted in a subsample of 247 children.
      Data from a free running test and a methacholine inhalation challenge test were
      available in 218 children. The diagnosis of asthma was confirmed by a paediatric
      allergist. RESULTS: Despite their high specificity (>0.97), BHR tests did not
      significantly improve the diagnostic accuracy after the symptom history: area
      under the receiver operator characteristic (ROC) curve was 0.90 for a logistic
      regression model with four symptoms and 0.94 for the symptoms with free running
      test and methacholine inhalation challenge results. On the other hand, BHR tests
      had low sensitivity (0.35-0.47), whereas several symptoms had both high
      specificity (>0.97) and sensitivity (>0.7) in relation to clinical asthma, which
      makes them a better tool for asthma epidemiology than BHR. CONCLUSIONS: Symptom
      history still forms the basis for defining asthma in both clinical and
      epidemiological settings. BHR tests only marginally increased the diagnostic
      accuracy after symptom history had been taken into account. The diagnosis of
      childhood asthma should not therefore be overlooked in symptomatic cases with no
      objective evidence of BHR. Moreover, BHR should not be required for defining
      asthma in epidemiological studies.

PMID- 11828041
TI  - Relaxation therapies for asthma: a systematic review.
AB  - BACKGROUND: Emotional stress can either precipitate or exacerbate both acute and
      chronic asthma. There is a large body of literature available on the use of
      relaxation techniques for the treatment of asthma symptoms. The aim of this
      systematic review was to determine if there is any evidence for or against the
      clinical efficacy of such interventions. METHODS: Four independent literature
      searches were performed on Medline, Cochrane Library, CISCOM, and Embase. Only
      randomised clinical trials (RCTs) were included. There were no restrictions on
      the language of publication. The data from trials that statistically compared the
      treatment group with that of the control were extracted in a standardised
      predefined manner and assessed critically by two independent reviewers. RESULTS:
      Fifteen trials were identified, of which nine compared the treatment group with
      the control group appropriately. Five RCTs tested progressive muscle relaxation
      or mental and muscular relaxation, two of which showed significant effects of
      therapy. One RCT investigating hypnotherapy, one of autogenic training, and two
      of biofeedback techniques revealed no therapeutic effects. Overall, the
      methodological quality of the studies was poor. CONCLUSIONS: There is a lack of
      evidence for the efficacy of relaxation therapies in the management of asthma.
      This deficiency is due to the poor methodology of the studies as well as the
      inherent problems of conducting such trials. There is some evidence that muscular
      relaxation improves lung function of patients with asthma but no evidence for any
      other relaxation technique.

PMID- 11828042
TI  - Expiratory muscle endurance in chronic obstructive pulmonary disease.
AB  - BACKGROUND: A reduction in expiratory muscle (ExM) endurance in patients with
      chronic obstructive pulmonary disease (COPD) may have clinically relevant
      implications. This study was carried out to evaluate ExM endurance in patients
      with COPD. METHODS: Twenty three patients with COPD (FEV(1) 35 (14)% predicted)
      and 14 matched controls were studied. ExM endurance was assessed using a method
      based on the use of an expiratory threshold valve which includes two steps. In
      step 1 the load is progressively increased (50 g every 2 minutes) until task
      failure is reached, and the pressure generated against the highest tolerated load
      is defined as the maximal expiratory sustainable pressure (Pthmax). In step 2
      subjects breathe against a submaximal constant load (80% of Pthmax) and the time
      elapsed until task failure is termed the expiratory endurance time (Tth(80)). In
      addition, the strength of peripheral muscles (handgrip, HGS) and respiratory
      muscles (maximal inspiratory and expiratory pressures, PImax and PEmax,
      respectively) was evaluated. RESULTS: Patients with COPD had lower ExM strength
      and endurance than controls: PEmax 64 (19)% predicted v 84 (14)% predicted (mean
      difference 20%; 95% confidence intervals (CI) 14 to 39); Pthmax 52 (27) v 151
      (46) cm H(2)O (mean difference 99, 95% CI 74 to 123); and Tth(80) 9.4 (6.3) v
      14.2 (7.4) min (mean difference 4.8, 95% CI 1.0 to 10.4; p<0.01 for all).
      Interestingly, ExM endurance directly correlated with both the severity of
      airways obstruction (Pthmax with FEV(1), r=0.794, p<0.01) and the reduction in
      strength observed in different muscle groups (Pthmax with HG, PImax or PEmax,
      r=0.550, p<0.05; r=0.583, p<0.001; and r=0.584, p<0.001, respectively).
      CONCLUSIONS: ExM endurance is decreased in patients with COPD. This impairment is
      proportional to the severity of the disease and is associated with lower strength
      in different muscle groups. This suggests that systemic effects are implicated in
      the impairment observed in ExM function.

PMID- 11828044
TI  - Outcome of Burkholderia cepacia colonisation in an adult cystic fibrosis centre.
AB  - BACKGROUND: Colonisation with Burkholderia cepacia is a poor prognostic indicator
      in subjects with cystic fibrosis (CF), but outcome prediction is impossible since
      patients are colonised by different strains with differing pathogenicity. The
      clinical course of a large cohort of CF patients colonised with UK epidemic
      (ET12) B cepacia was followed for 5 years and compared with that of the remaining
      patients in the clinic. METHODS: Pulmonary function, nutritional state, and lung
      pathogen colonisation were recorded for 5 years before December 1997 or death for
      all 107 patients who had attended the Liverpool adult CF clinic since 1993. For
      each patient a time line from study entry to date of death or 1997 was
      constructed. In 1993 potential risk factors including age and sex were subjected
      to Cox proportional hazards analysis using the end point of mortality as the
      outcome variable. The analysis was supplemented by time varying covariables that
      described the change in FEV(1), BMI, and colonisation status across time, and the
      excess risk associated with B cepacia colonisation was calculated. Subsequently,
      in those patients who died between 1993 and 1997, predictive factors for death
      were compared within groups using complete 5 year data. RESULTS: Thirty seven
      patients had been colonised by epidemic B cepacia and these patients had four
      times the mortality of the remainder (p<0.01). In 1993 univariate predictors of
      mortality were age (alive 19.6 (0.64) v dead 23.8 (1.44); p<0.005) and baseline
      FEV(1) (alive 68.6 (2.5)% predicted v dead 43.2 (4.8)%; p<0.001) with a trend for
      BMI (p=0.07). However, following time varying covariate Cox proportional hazards
      analysis, only lower FEV(1) (hazards ratio 1.1, 95% confidence limits 1.06 to
      1.14; p<0.001) and colonisation with B cepacia (hazards ratio 7.92, confidence
      limits 2.65 to 23.69; p<0.001) were identified as significant factors for death.
      Surviving B cepacia patients had similar initial lung function to the remaining
      surviving patients but had an accelerated loss of lung function over the study
      period (colonised -1.9% predicted per year v non-colonised -0.3% predicted per
      year; p<0.05). Deceased patients colonised with B cepacia had better spirometric
      results than the remaining deceased patients 5 years before death (p<0.05) but
      lost lung function at a greater rate than non-colonised patients (colonised -6.2%
      predicted per year v non-colonised -1.9% predicted per year; p<0.05).
      CONCLUSIONS: This study confirms the excess mortality associated with epidemic B
      cepacia colonisation and shows that those with poor spirometric values are at the
      greatest risk.

PMID- 11828043
TI  - Clinical audit indicators of outcome following admission to hospital with acute
      exacerbation of chronic obstructive pulmonary disease.
AB  - BACKGROUND: The 1997 BTS/RCP national audit of acute chronic obstructive
      pulmonary disease (COPD) in terms of process of care has previously been
      reported. This paper describes from the same cases the outcomes of death,
      readmission rates within 3 months of initial admission, and length of stay.
      Identification of the main pre-admission predictors of outcome may be used to
      control for confounding factors in population characteristics when comparing
      performance between units. METHODS: Data on 74 variables were collected
      retrospectively using an audit proforma from patients admitted to UK hospitals
      with acute COPD. Important prognostic variables for the three outcome measures
      were identified by relative risk and logistic regression was used to place these
      in order of predictive value. RESULTS: 1400 admissions from 38 acute hospitals
      were collated. 14% of cases died within 3 months of admission with variation
      between hospitals of 0-50%. Poor performance status, acidosis, and the presence
      of leg oedema were the best significant independent predictors of death. Age
      above 65, poor performance status, and lowest forced expiratory volume in 1
      second (FEV(1)) tertile were the best predictors of length of stay (median 8
      days). 34% of patients were readmitted (range 5-65%); lowest FEV(1) tertile,
      previous admission, and readmission with five or more medications were the best
      predictors for readmission. CONCLUSIONS: Important predictors of outcome have
      been identified and formal recording of these may assist in accounting for
      confounding patient characteristics when making comparisons between hospitals.
      There is still wide variation in outcome between hospitals that remains
      unexplained by these factors. While some of this variance may be explained by
      incomplete recording of data or patient factors as yet unidentified, it seems
      likely that deficiencies in the process of care previously identified are
      responsible for poor outcomes in some units.

PMID- 11828045
TI  - Expression of protease activated receptor-2 (PAR-2) in central airways of smokers
      and non-smokers.
AB  - BACKGROUND: Protease activated receptor-2 (PAR-2) is a transmembrane G protein
      coupled receptor preferentially activated by trypsin and tryptase. The protease
      activated receptors play an important role in most components of injury responses
      including cell proliferation, migration, matrix remodelling, and inflammation.
      Cigarette smoking causes an inflammatory process in the central airways,
      peripheral airways, lung parenchyma, and adventitia of pulmonary arteries.
      METHODS: To quantify the expression of PAR-2 in the central airways of smokers
      and non-smokers, surgical specimens obtained from 30 subjects undergoing lung
      resection for localised pulmonary lesions (24 with a history of cigarette smoking
      and six non-smoking control subjects) were examined. Central airways were
      immunostained with an antiserum specific for PAR-2 and PAR-2 expression was
      quantified using light microscopy and image analysis. RESULTS: PAR-2 expression
      was found in bronchial smooth muscle, epithelium, glands, and in the endothelium
      and smooth muscle of bronchial vessels. PAR-2 expression was similar in the
      central airways of smokers and non-smokers. When smokers were divided according
      to the presence of symptoms of chronic bronchitis and chronic airflow limitation,
      PAR-2 expression was increased in smooth muscle (median 3.8 (interquartile range
      2.9-5.8) and 1.4 (1.07-3.4) respectively); glands (33.3 (18.2-43.8) and 16.2
      (11.5-22.2), respectively); and bronchial vessels (54.2 (48.7-56.8) and 40.0 (36
      40.4), respectively) of smokers with symptoms of chronic bronchitis with normal
      lung function compared with smokers with chronic airflow limitation (COPD), but
      the increase was statistically significant (p<0.005) only for bronchial vessels.
      CONCLUSIONS: PAR-2 is present in bronchial smooth muscle, glands, and bronchial
      vessels of both smokers and non-smokers. An increased expression of PAR-2 was
      found in bronchial vessels of patients with bronchitis compared with those with
      COPD.

PMID- 11828046
TI  - Pulmonary tuberculosis among political asylum seekers screened at Heathrow
      Airport, London, 1995-9.
AB  - BACKGROUND: Over 50% of cases of tuberculosis (TB) in the UK occur in people born
      overseas, and new entrants to the country are screened for TB. A study was
      undertaken to determine the prevalence and disease characteristics of pulmonary
      TB in new entrants to the UK seeking political asylum. METHODS: A retrospective
      analysis of the results of screening 53 911 political asylum seekers arriving at
      Heathrow Airport between 1995 and 1999 was performed by studying Airport Health
      Control Unit records and hospital medical records. Outcome measures were chest
      radiograph abnormalities, sputum smear, culture, and drug resistance data for
      Mycobacterium tuberculosis. RESULTS: The overall prevalence of active TB in
      political asylum seekers was 241 per 100 000. There were large variations in
      prevalences of TB between asylum seekers from different regions, with low rates
      from the Middle East and high rates from the Indian subcontinent and sub-Saharan
      Africa. The frequency of drug resistance was high; 22.6% of culture positive
      cases were isoniazid resistant, 7.5% were multidrug resistant (resistant to both
      isoniazid and rifampicin), and 4% of cases diagnosed with active disease had
      multidrug resistant TB. CONCLUSIONS: The prevalence rate of TB in political
      asylum seekers entering the UK through Heathrow Airport is high and more M
      tuberculosis isolates from asylum seekers are drug resistant than in the UK
      population. Extrapolating these figures, it is estimated that 101 political
      asylum seekers with active pulmonary TB enter the UK every year, of whom about 25
      would have smear positive disease.

PMID- 11828047
TI  - Cell specific expression of peroxiredoxins in human lung and pulmonary
      sarcoidosis.
AB  - BACKGROUND: Six proteins of the peroxiredoxin (Prx) family have recently been
      characterised which have the capacity to decompose hydrogen peroxide in vivo and
      in vitro. These proteins may have an important role in the protection of human
      lung against endogenous and exogenous oxidant stress. However, the expression and
      distribution of these proteins in healthy human lung and diseased lung tissue is
      unknown. METHODS: The cell specific expression of Prxs in healthy lung tissue
      from four non-smokers and in parenchymal tissue from 10 subjects with pulmonary
      sarcoidosis was investigated by immunohistochemistry, and expression of these
      proteins in various cultured lung cells and cells of bronchoalveolar lavage (BAL)
      fluid of controls and patients with sarcoidosis was assessed by Western blot
      analysis. RESULTS: All six Prxs could be synthesised in cultured human lung
      cells. The bronchial epithelium showed moderate to high expression of Prxs I,
      III, V and VI, the alveolar epithelium expressed mainly Prxs V and VI, and
      alveolar macrophages expressed mainly Prxs I and III. Granulomas of subjects with
      sarcoidosis expressed mainly Prxs I and III. Samples of BAL fluid from controls
      and from subjects with sarcoidosis had very similar findings, except that Prxs II
      and III had a tendency for increased immunoreactivity in sarcoidosis tissue.
      CONCLUSIONS: Prxs I, III, V, and VI, in particular, have prominent and cell
      specific expression in human lung tissue. High expression of Prxs I and III in
      granulomas and alveolar macrophages of sarcoidosis parenchyma may have a
      significant effect on the oxidant burden and the progression of lung injury in
      this disease.

PMID- 11828048
TI  - Wheeze not current asthma affects quality of life in young adults with asthma.
AB  - BACKGROUND: A study was undertaken to investigate quality of life in asthma,
      defined by differing criteria, to see which may be most appropriate in
      epidemiological studies. METHODS: The 426 adults were participants in the follow
      up phase of the European Community Respiratory Health Survey (ECRHS) in
      Melbourne. As part of the laboratory visit, participants completed the SF-36
      quality of life questionnaire, a detailed respiratory questionnaire, and
      underwent lung function testing. RESULTS: Both the physical component summary and
      the mental component summary scores were significantly worse in those with wheeze
      in the previous 12 months than in those without wheeze. Only the mental component
      summary score was significantly worse in those with current asthma than in those
      without. In contrast, in those with current asthma or bronchial hyperreactivity
      only, neither of the summary scales was significantly different between cases and
      controls. CONCLUSIONS: Quality of life is severely impaired in individuals with
      wheeze in the previous 12 months while individuals with current asthma or
      bronchial hyperreactivity alone did not appear to have significantly reduced
      quality of life.

PMID- 11828049
TI  - Patients' and carers' preferences in two models of care for acute exacerbations
      of COPD: results of a randomised controlled trial.
AB  - BACKGROUND: Patients with an acute exacerbation of chronic obstructive pulmonary
      disease (COPD) were randomised to either hospital at home (HaH) or inpatient
      management, and patient and carer preferred site of management and satisfaction
      with care received in the two arms was determined. METHODS: Emergency admissions
      with an acute exacerbation of COPD were randomised to inpatient care or HaH care.
      After discharge an independent observer administered a questionnaire to both
      patients and carers on the preferred site of care and scored satisfaction with
      the care received. RESULTS: Of 60 patients recruited, 30 were randomised to
      receive HaH care. Retrospective patient preference for HaH care was 96.3% in the
      domiciliary arm and 59.3% in the conventional arm; carer preference figures were
      85.7% and 42.9%, respectively. There was a higher preference for domiciliary care
      by both patients and carers in the HaH arm than in the inpatient arm (p=0.001 and
      p=0.01, respectively). Patients recorded equal satisfaction with care in the two
      arms (88.1% in the conventional arm, 91.7% in the domiciliary arm); carer scores
      were 91.3% and 91.9%, respectively. CONCLUSIONS: The results of this study show
      that both patients and carers were significantly more likely to prefer
      domiciliary care if they were in the HaH arm. Since patients had to be willing to
      be looked after at home, both patients' and carers' perceptions of the benefits
      of HaH care were reinforced by their experience. HaH care of acute exacerbations
      of COPD is the preferred option in suitable patients.

PMID- 11828050
TI  - The pulmonary physician in critical care * 2: oxygen delivery and consumption in
      the critically ill.
AB  - Early detection and correction of tissue hypoxia is essential if progressive
      organ dysfunction and death are to be avoided. However, hypoxia in individual
      tissues or organs caused by disordered regional distribution of oxygen delivery
      or disruption of the processes of cellular oxygen uptake and utilisation cannot
      be identified from global measurements. Regional oxygen transport and cellular
      utilisation have an important role in maintaining tissue function. When tissue
      hypoxia is recognised, treatment must be aimed at the primary cause. Supplemental
      oxygen may be life saving in some situations but cannot correct inadequate oxygen
      delivery caused by a low cardiac output or impaired ventilation. Recent
      innovations include artificial oxygen carrying proteins and "haemoglobin"
      molecules designed to improve tissue blood flow by reducing viscosity. Regulating
      cell metabolism using different substrates or drugs has so far been poorly
      explored but is an exciting area for further research. A minimum level of global
      oxygen delivery and perfusion pressure must be maintained in the critically ill
      patient with established "shock", but advances in the understanding and control
      of regional distribution and other "downstream" factors in the oxygen cascade are
      needed to improve outcome in these patients.

PMID- 11828052
TI  - Montelukast and Churg-Strauss syndrome.
AB  - Several cases of eosinophilic conditions including Churg-Strauss syndrome (CSS)
      have recently been reported in asthmatic patients being treated with
      antileukotriene receptor antagonists. One patient with CSS who experienced a
      clinical relapse after treatment with montelukast and two asthmatic patients who
      developed CSS while receiving montelukast treatment are described. In one case
      reduction in the dose of oral steroid preceded the onset of CSS. To our
      knowledge, no case of CSS relapse has previously been reported in association
      with leukotriene antagonists.

PMID- 11828053
TI  - AHR in asthma.

PMID- 11828054
TI  - One fibre or many; what causes mesothelioma?

PMID- 11828051
TI  - Eosinophilic bronchitis: clinical manifestations and implications for treatment.
AB  - Airway inflammation with eosinophils is now reported to occur not only in asthma
      but in other airway diseases such as cough variant asthma, chronic cough, atopic
      cough, episodic symptoms without asthma, allergic rhinitis, and COPD. Although
      the prevalence of eosinophilic bronchitis (EB) is less than in asthma, the
      causes, mechanisms and treatment of EB in these conditions appears to be similar
      to asthma where allergen induced IL-5 secretion and symptoms are readily
      responsive to inhaled corticosteroids. The prognosis of EB without asthma is not
      known but it may be a precursor for asthma and, if so, recognition of this
      syndrome may permit effective treatment and reduction in the rising prevalence of
      asthma. Induced sputum analysis allows recognition of EB in clinical practice.
      The place of the asthma treatment paradigm with early and sustained
      corticosteroid treatment needs to be defined in EB without asthma. Airway wall
      remodelling can occur in rhinitis, COPD, and cough variant asthma with EB. The
      mechanisms and long term implications of this complication in EB without asthma
      need to be clarified.

PMID- 11828055
TI  - BMD and airways disease.

PMID- 11828056
TI  - Statement on malignant mesothelioma in the UK.

PMID- 11828057
TI  - Asymptomatic pulmonary involvement in RA.

PMID- 11828058
TI  - Mesothelioma.

PMID- 11828059
TI  - Cervical screening: lessons from the Australian experience.

PMID- 11828060
TI  - Cervical smear screening: questionnaire study of histories and attitudes of
      patients with squamous cervical carcinoma.
AB  - OBJECTIVE: To determine why invasive cervical carcinoma still occurs despite the
      availability of cervical smear screening services. DESIGN: Questionnaire survey
      and retrospective study of patient records of women who attended a gynaecological
      oncology out-patients clinic from 13 February 1997 to 30 June 1997. SETTING:
      Public hospital, Hong Kong. PATIENTS: Ninety-nine women (median age, 53 years;
      range, 30-79 years) who gave a history of squamous cervical carcinoma. MAIN
      OUTCOME MEASURES: The date of the last cervical smear test prior to the
      development of cervical carcinoma; reasons for non-attendance; attitudes to
      screening; and the stage and histological diagnosis of disease. RESULTS: Only 19
      (19.2%) of the 99 patients had received routine cervical smear testing during the
      previous 3 years prior to their disease; 76 (76.8%) had not been tested within
      the past 10 years. The major reasons for not having been tested included being
      unaware that cervical carcinoma is preventable by screening or can be
      asymptomatic, being too busy to go for screening, and not knowing where to go for
      screening. After receiving treatment, 17 (17.2%) of the 99 patients still thought
      screening was unnecessary and 20 (20.2%) had no idea how frequently smears should
      be taken. CONCLUSION: The greatest barrier to effective cervical screening is
      patient ignorance. Public education about cervical smear screening in Hong Kong
      is needed.

PMID- 11828061
TI  - Evaluation of the ThinPrep Papanicolaou test in clinical practice: 6-month study
      of 16,541 cases with histological correlation in 220 cases.
AB  - OBJECTIVE: To evaluate the liquid-based ThinPrep Papanicolaou test. DESIGN:
      Prospective comparison of the ThinPrep test with the conventional Papanicolaou
      test. SETTING: Cervical smear specimens sent to a private practice, Hong Kong.
      PATIENTS: A total of 16,541 ThinPrep test specimens and 7258 conventional
      Papanicolaou smears from Hong Kong women who had been screened for cervical
      cancer between mid-July 1998 and mid-January 1999. MAIN OUTCOME MEASURES:
      Specimen adequacy, endocervical cell content, epithelial cell abnormalities, and
      micro-organisms present in both types of cervical smears; histological diagnosis
      of cervical biopsy specimens of women who had the ThinPrep test. RESULTS:
      Compared with the conventional Papanicolaou smear test, the ThinPrep test showed
      a reduction in the frequency of 'unsatisfactory' (0.56% versus 1.36%; P<0.01),
      'satisfactory but limited' (1.67% versus 15.87%; P<0.01), and 'atypical squamous
      cells of undetermined significance' reports (1.72% versus 3.64%; P<0.01). The
      ThinPrep test was also more effective at detecting squamous intraepithelial
      lesions, showing a 58% increase for low-grade lesions (2.66% versus 1.68%;
      P<0.01) and 28% increase for high-grade lesions (1.71% versus 1.34%; P<0.01). The
      sensitivity and positive predictive value of the ThinPrep system were 97.5% and
      94.2%, respectively. The liquid-based method yielded a higher percentage of
      samples that contained endocervical cells compared with conventional smear
      specimens (70.57% versus 51.23%; P<0.001). CONCLUSIONS: The ThinPrep test has a
      high sensitivity and positive predictive value. The ThinPrep test gives higher
      quality specimens and has a higher detection rate of squamous intraepithelial
      lesions than the conventional Papanicolaou smear test. The drawbacks of the
      liquid-based system, however, pertain to cost and the additional procedures and
      training needed.

PMID- 11828062
TI  - Clinical and pathological characteristics of patients with glomerular diseases at
      a university teaching hospital: 5-year prospective review.
AB  - OBJECTIVE: To examine the prevalence of glomerular disease in Hong Kong. DESIGN:
      Prospective review. SETTING: University teaching hospital, Hong Kong. PATIENTS:
      All patients who presented with suspected glomerular disease from 1993 through
      1997. MAIN OUTCOME MEASURES: Histopathological diagnosis from biopsy examination
      and clinical features of presentation. RESULTS: A total of 1629 consecutive
      percutaneous renal biopsies of native kidneys showed glomerular disease in 1413
      cases. The most common clinical indication for renal biopsy was persistent
      proteinuria (n=735; 52.0%), while the most frequently found glomerular lesion was
      immunoglobulin A nephropathy (n=338; 23.9%). Minimal-change nephrotic syndrome
      (n=125; 8.8%) and immunoglobulin M nephropathy (n=11; 0.8%), were the most common
      glomerular diseases that presented with nephrotic syndrome. The male to female
      ratio for lupus nephritis was 1:14 (n=290), whereas for minimal-change nephrotic
      syndrome, the ratio was 1.8:1 (n=125). Immunoglobulin A nephropathy and
      membranous glomerulonephritis (n=117) affected approximately equal numbers of
      male and female patients. Familial fibrillary glomerulonephritis, a disease
      hitherto unknown in Hong Kong, was diagnosed in two siblings. CONCLUSION:
      Immunoglobulin A nephropathy was the most common glomerular disease in this
      survey and represents an important cause of end-stage renal failure in the Hong
      Kong population.

PMID- 11828063
TI  - Impairment of hand function and loss of earning capacity after occupational hand
      injury: prospective cohort study.
AB  - OBJECTIVE: To examine the loss of earning capacity and permanent impairment of a
      cohort of male patients who had experienced finger amputation due to occupational
      injury. DESIGN: Prospective cohort study. SETTING: University teaching hospital,
      Hong Kong. PATIENTS: Twenty-eight male patients aged 26 to 55 years who presented
      with work-related finger amputations in their dominant right hand from 1990
      through 1991. MAIN OUTCOME MEASURES: Type and extent of amputation, and hand
      function before and after (mean, 11 months; range, 8-6 months) the patients'
      return to work. Assessment results were compared with patients' percentage loss
      of earning capacity as calculated using the scale described in the Employees'
      Compensation Ordinance of Hong Kong. RESULTS: Patients with injuries that
      corresponded to a loss of earning capacity of 12% or greater had a significant
      impairment in their hand function (P<0.05); the hand function of this group after
      their return to work significantly improved (P<0.05). There were no significant
      differences between the loss of earning capacity scores as calculated by the Hong
      Kong, American Medical Association, or Indian Medical Association scales.
      CONCLUSION: Patients whose loss of earning capacity of 12% or greater are likely
      to have significant long-term impairments of hand function. Thus, a more
      intensive rehabilitation programme should be provided to this group.

PMID- 11828064
TI  - Cerebral palsy and the birth process.
AB  - OBJECTIVE: To review the relationship between cerebral palsy and the birth
      process. DATA SOURCES: Medline and non-Medline literature search and personal
      experience. STUDY SELECTION: Articles that commented on the routinely used
      markers of foetal distress, such as abnormal foetal heart rate, meconium-stained
      liquor, and foetal acidosis. DATA EXTRACTION: Data were extracted and reviewed
      independently by both authors. DATA SYNTHESIS: The use of meconium alone as a
      predictor of cerebral palsy has a high false-positive rate of up to 99.6%. No
      specific foetal heart rate pattern that can accurately predict subsequent
      neurological impairment, and a low Apgar score is not by itself an indication of
      intrapartum asphyxia. The presence of encephalopathy in a neonate after birth and
      the association of multi-organ system dysfunction are important clues to the
      prior occurrence of foetal asphyxia. CONCLUSION: Cerebral palsy can be caused by
      asphyxia associated with the birth process. To be able to attribute cerebral
      palsy to peripartum asphyxia, there should be a sequence of signs during labour,
      delivery, and the perinatal period. Honest and sympathetic discussion between the
      obstetrician, paediatrician, and parents is critical throughout the counselling
      process.

PMID- 11828065
TI  - Eye care when using video display terminals.
AB  - OBJECTIVE: To examine the scientific data in the literature regarding eye
      problems and possible damage during the use of computer video display terminals.
      DATA SOURCES: Medline and non-Medline literature search and personal experience.
      STUDY SELECTION: Studies that provided evidence-based information about eye
      damage and eye care during the use of video display terminals were selected. DATA
      EXTRACTION: Data were extracted independently by multiple observers. DATA
      SYNTHESIS: Most studies have shown that the levels of ionizing and non-ionizing
      radiation that are emitted by video display terminals are not harmful to the
      human eye. Eye complaints associated with the use of video display terminals
      include the McCollough effect, accommodative spasm, 'dry eyes', and eye strain.
      Ergonomic considerations and good visual hygiene can help alleviate symptoms.
      CONCLUSION: There is currently no convincing evidence that shows that using video
      display terminals is harmful to the eye.

PMID- 11828066
TI  - Lung and heart-lung transplantation in Hong Kong.
AB  - OBJECTIVE: To review the donor and recipient selection criteria, surgical
      techniques, perioperative and post-operative management, and complications of
      lung/heart-lung transplantation. DATA SOURCES: Medline and non-Medline search of
      the relevant English literature, local data, and personal experience. STUDY
      SELECTION: Studies containing supporting evidence were selected. DATA EXTRACTION:
      Data were extracted and analysed independently by the authors. DATA SYNTHESIS:
      Lung/heart-lung transplantations are considered only for patients who have
      progressively disabling and end-stage disease. Numerous investigations of the
      recipient and rigorous matching between the donor and recipient are required.
      Factors such as maintaining the donor's haemodynamic stability, graft
      preservation, effective perioperative immunosuppression, and careful
      postoperative monitoring are key to a successful transplantation. Follow-up
      should include the home-monitoring of body weight, temperature, and spirometry,
      as well as regular chest X-rays, pulmonary function tests, and blood tests. So
      far, two double and two single lung transplantations, and one heart-lung
      transplantation have been performed in Hong Kong. CONCLUSION: Lung
      transplantation is an invaluable treatment modality for patients with end-stage
      lung disease.

PMID- 11828067
TI  - Cervical screening in the United Kingdom.
AB  - It has been more than 10 years since the cervical screening system in the United
      Kingdom was completely overhauled and a computerised call and recall system was
      introduced. The current programme is very healthy and dramatic improvements have
      been made over the past decade. The coverage of the screening programme in
      England has improved, and incidence and mortality rates have been reduced.
      Further improvements in compliance, rigorous auditing, and new technologies will
      likely yield more accurate, efficient, and cost-effective screening programmes in
      the next decade.

PMID- 11828068
TI  - Detecting cervical cancer: the European experience.
AB  - An effective cervical smear test does not equate to an effective screening
      programme. A major challenge in Europe has been to formulate efficient, cost
      effective, and balanced programmes, and to implement them. Improving
      participation and follow-up, and reducing the false-positive and false-negative
      rates are also important factors. This article discusses the process of
      implementing and maintaining effective screening programmes in European health
      care systems, comments on common pitfalls of such programmes, and suggests future
      directions.

PMID- 11828069
TI  - The impact of the type and screen test policy on hospital transfusion practice.
AB  - The requirements of pretransfusion testing have undergone repeated modification,
      and those of the type and screen policy are currently the most widely accepted to
      be standard. The type and screen test policy, together with the abbreviated
      crossmatch procedure, was implemented in the United Christian Hospital in January
      1997. This paper discusses the impact of the type and screen test policy on
      clinicians and patients, on the blood bank and hospital, and on the future of the
      hospital transfusion services.

PMID- 11828070
TI  - Leukocytes in blood transfusion: adverse effects and their prevention.
AB  - Leukocyte contamination during blood transfusion can cause many adverse effects,
      such as the transmission of cell-associated infectious agents, febrile non
      haemolytic reactions, graft-versus-host disease, and immunosuppression. While
      using leukodepleted blood components can minimise some of these adverse effects,
      the leukodepletion of all cellular blood components is costly. A more cost
      effective alternative would be to supply leukodepleted blood components to at
      risk patients only.

PMID- 11828071
TI  - A case of Castleman's disease mimicking a multicystic ovarian tumour.
AB  - We report on a case of solitary Castleman's disease that had an unusual
      presentation. A 29-year-old Filipino woman who had a history of intermittent
      right lower abdominal pain for several years was admitted to the Princess
      Margaret Hospital because of a sudden exacerbation of the abdominal pain.
      Ultrasonography had previously detected a multilocular right ovarian cyst of
      approximately 6.5 cm in diameter. Intra-operative findings, however, revealed a
      retroperitoneal presacral cystic tumour of approximately 7 cm in diameter, which
      was unrelated to the ovaries. The tumour was removed and found to be well defined
      and measure 7 x 5 x 4 cm. The cut surface revealed homogenous light-brown tissue
      at the periphery. The central part showed cystic spaces of 1- to 3-cm diameter.
      Histological examination of the tumour led to the diagnosis of hyaline vascular
      type Castleman's disease. Cystic spaces were visible within the infarcted tissue;
      extensive cystic changes in Castleman's disease are unusual and may have caused
      the diagnostic difficulty.

PMID- 11828072
TI  - Selective posterior rhizotomy: results of five pilot cases.
AB  - We report on two patients with spastic quadriplegia and three patients with
      spastic diplegia who underwent selective posterior rhizotomy. The mean period of
      follow-up was 15 months (range, 12-21 months). The patients were assessed
      preoperatively and at 2 weeks, 3 months, 6 months, and 1 year after surgery.
      Tests included those for muscle tone (using a modified Ashworth scale), range of
      passive movement, functional status, and gait pattern. Muscle tone was reduced
      substantially after the procedure, and the range of passive movement was
      increased. Both the dependent and independent ambulators showed an increment in
      their walking velocity and stride length. There were no postoperative
      complications apart from mild fever and the treatment was well tolerated by both
      patients and parents. There was no return of spasticity in any of the patients
      during follow-up. The reduced spasticity resulted in better motor performance,
      and patients felt more comfortable with their daily activities. We conclude that
      selective posterior rhizotomy should be considered for those patients who have
      cerebral palsy and are disabled by spasticity.

PMID- 11828073
TI  - Use of intravenous immunoglobulin in a patient with refractory myasthenia gravis
      associated with malignant thymoma.
AB  - We report on a case of refractory myasthenia gravis that was managed by using
      intravenous immunoglobulin. A 35-year-old Chinese woman with malignant thymoma
      associated myasthenia gravis was treated by total thymectomy, followed by
      chemotherapy. Thirty months later, she developed respiratory failure and required
      mechanical ventilation for 2 months. A course of intravenous immunoglobulin was
      given and her condition improved significantly. Two weeks later, the patient
      became ambulatory, was prescribed oral pyridostigmine, and was discharged home.

PMID- 11828074
TI  - The cervical smear test in the next millennium.
AB  - This paper traces the cervical Papanicolaou smear test from the seminal work of
      George Papanicolaou undertaken more than 70 years ago, to the present use of
      computer technology to examine cervical smears. However, to successfully detect
      cervical cancer and precursor lesions, the standard of the specimens, as well as
      that of the screening laboratory, must be of the highest order so that false
      negative results are eliminated. Newer sampling devices, techniques for improving
      specimen quality, computerised laboratory technology, and the need for laboratory
      accreditation are also discussed. The Papanicolaou test is the most successful
      test invented for cancer prevention but despite this, up to two thirds of Hong
      Kong women have not had a test. There is a need for more public health education
      directed at women so that there is a greater awareness of the importance of
      disease prevention, with an emphasis on cancer prevention. The implementation of
      a cervical screening programme in the new millennium will ensure that women
      receive all the benefits that the Papanicolaou smear test can confer.

PMID- 11828075
TI  - Ischaemic bowel detected as hepatic portal venous gas on a chest X-ray.

PMID- 11828077
TI  - Chemotherapy for non-small-cell cancer: cost and toxicity?

PMID- 11828076
TI  - Will transfusion errors due to human factors ever be eliminated?

PMID- 11828078
TI  - Non-screen Papanicolaou smears taken by colposcopy nurses: a prospective study.

PMID- 11828079
TI  - Halnan Lecture 1998. Medicine: quo vadis.
AB  - Medicine has made rapid progress but has it lost its direction? Medicine is but
      one of the factors on which the health of a community depends; others include
      sanitation, housing, education, and life-style. Developments in medical education
      and practice must take into account the needs of society, changes in demography,
      patient expectations, costs, and the importance of preventive medicine. While the
      humanities, communication skills, and medical economics are important, these
      should not be taught at the expense of a sound core curriculum and clinical
      skills, which may be declining. Can human kindness and understanding be taught?
      Role models may help, but are their numbers sufficient? Postgraduate
      organisations have been successful in vocational training, but 'professionalism'
      must be further nurtured. This concerns doctors' responsibilities and
      relationships with patients, colleagues, the profession, and society. Specialists
      and subspecialists are needed but so are the 'generalists'. The education and
      training of doctors must be done in the context of the overall training of health
      care personnel. The Hong Kong Academy of Medicine and its Colleges must have a
      significant voice in making decisions and policies that affect health and medical
      matters. A patient should be a satisfied patient and not a statistic or a client.
      Where is medicine heading? Let us pause, think, and then act to lead it straight
      ahead.

PMID- 11828080
TI  - Dilead mercury chromate(VI), Pb2HgCrO6.
AB  - The structure of Pb(2)HgCrO(6) (space group P-1) can be described as consisting
      of isolated [CrO(4)](2-) tetrahedra and nearly linear [HgO(2)](2-) dumb-bells,
      which form layers of composition [HgCrO(6)](4-). These are intercalated with
      corrugated pseudo-hexagonal Pb(2+) layers. The Pb(2+) cation is stereochemically
      active and has coordination 3+5.

PMID- 11828081
TI  - Bismuth octaborate, Bi2B8O15.
AB  - In the title compound, Bi(2)B(8)O(15), the Bi atom is coordinated to five or six
      O atoms. The B atoms exhibit two kinds of hybridization, sp(2) and sp(3), seen in
      the BO(3) triangles and BO(4) tetrahedra, respectively. Three BO(3) triangles are
      connected to form a B(3)O(6) planar ring. All atoms in the structure are
      connected together to form an infinite three-dimensional network.

PMID- 11828082
TI  - catena-Poly[[[tetrakis(1-methylimidazole-kappaN3)copper(II)]-mu2-sulfato
      kappa2O:O'] acetonitrile hemisolvate sesquihydrate].
AB  - The title compound, [Cu(C(4)H(8)N(2))(4)]SO(4).0.5CH(3)CN.1.5H(2)O, consists of a
      double chain wherein the Cu centres are octahedrally coordinated by four 1
      methylimidazole ligands in the equatorial plane and by two axial sulfate ions
      which act as bridges between the Cu centres. The Cu-N bond lengths lie between
      1.9929(14) and 2.0226(14)A, but the Cu-O bond distances are longer, with values
      between 2.3496(13) and 2.8276(14)A. The water molecules participate in the
      formation of a network of hydrogen bonds of significance in maintaining the
      connectivity of the structure.

PMID- 11828083
TI  - (Eta5-cyclopentadienyl)(p
      fluorophenoxo)(nitrosyl)(trimethylsilylmethyl)molybdenum(II).
AB  - The title complex, [Mo(C(5)H(5))(C(6)H(4)FO)(C(4)H(11)Si)(NO)], is formed by
      reacting CpMo(NO)(CH(2)SiMe(3))(2), where Cp is cyclopentadienyl, with one
      equivalent of p-FC(6)H(4)OH. The complex exhibits the expected piano-stool
      molecular structure, with a linear nitrosyl ligand [Mo-N-O 168.2(2) degree]
      having Mo-N and N-O distances of 1.764(2) and 1.207(3)A, respectively. The
      phenoxo Mo-O distance of 1.945(2)A is suggestive of some multiple-bond character.

PMID- 11828084
TI  - Two new [Ni(tren)2]2+ complexes: [Ni(tren)2]Cl2 and [Ni(tren)2]WS4.
AB  - Both title compounds, bis[tris(2-aminoethyl)amine]nickel(II) dichloride,
      [Ni(tren)(2)]Cl(2), (I), and bis[tris(2-aminoethyl)amine]nickel(II)
      tetrathiotungstate, [Ni(tren)(2)]WS(4), (II), contain the [Ni(tren)(2)](2+)
      cation [tren is tris(2-aminoethyl)amine, C(6)H(18)N(4)]. The tren molecule acts
      as a tridentate ligand around the central Ni atom, with the remaining primary
      amine group not bound to the central atom. In (I), Ni(2+) is located on a centre
      of inversion surrounded by one crystallographically independent tren molecule. In
      the [Ni(tren)(2)](2+) cation of (II), the Ni atom is bound to two
      crystallographically independent tren molecules. The Ni atoms in the
      [Ni(tren)(2)](2+) complexes are in a distorted octahedral environment consisting
      of six N atoms from the chelating tren molecules. The counter-ions are chloride
      anions in (I) and the tetrahedral [WS(4)](2-) anion in (II). Hydrogen bonding is
      observed in both compounds.

PMID- 11828085
TI  - fac-Tricarbonyl[hydroxybis(2-pyridyl)methanolato-kappa3N,O,N']rhenium(I).
AB  - The Re(I) centre in the title compound, [Re(C(11)H(9)N(2)O(2))(CO)(3)] or fac
      Re(CO)(3)(dpkO,OH) [dpkO,OH is hydroxybis(2-pyridyl)methanolato], (I), is in a
      pseudo-octahedral environment in which the major distortion is due to the
      constraints associated with the tridentate binding of the dpkO,OH anion. The
      carbonyl groups are orthogonal, with an average C-Re-C angle of 90.2(3) degree.
      The molecules pack in stacks of antiparallel tapes of (I) interlocked via a
      network of hydrogen bonds.

PMID- 11828086
TI  - Disodium pamidronate.
AB  - The title compound, disodium 3-ammonium-1-hydroxypropylidene-1,1-bisphosphonate
      pentahydrate, 2Na(+).C(3)H(9)NO(7)P(2)(2-).5H(2)O, is used for the diagnosis and
      treatment of a number of bone disorders. In the solid state, disodium pamidronate
      shows zwitterionic character and has four different modes of chelation to sodium.
      The metal is octahedrally coordinated by zwitterion and water O atoms. Both
      coordination to sodium and hydrogen bonding determine the packing in the crystal,
      which comprises columns lying parallel to the crystallographic a axis.

PMID- 11828087
TI  - (Mu-oxalato-O1,O2:O1',O2')bis[aqua(diethylenetriamine)nickel(II)]
      bis(hexafluorophosphate) dihydrate.
AB  - The title compound,
      [Ni(2)(C(2)O(4))(C(4)H(13)N(3))(2)(H(2)O)(2)](PF(6))(2).2H(2)O, contains a
      dinuclear oxalato-bridged nickel(II) complex cation. The structure determination
      reveals the presence of a centrosymmetric binuclear complex where the oxalate
      ligand is coordinated in a bis-bidentate mode to the Ni atoms. The distorted
      octahedral environment of each Ni atom is completed by the three N atoms of the
      diethylenetriamine ligand in a fac arrangement and by one O atom from a water
      molecule. PF(6)(-) acts as counter-anion. A two-dimensional network of hydrogen
      bonds links the cations and anions and stabilizes the structure.

PMID- 11828088
TI  - First- and second- sphere coordination of the uranyl ion by bis[2-(2
      hydroxyphenoxy)ethoxy]ethane.
AB  - Uranyl nitrate hexahydrate reacts with bis[2-(2-hydroxyphenoxy)ethoxy]ethane
      (C(18)H(22)O(6)), denoted LH(2) hereafter, in the presence of triethylamine to
      give triethylammonium aqua[2,2'-(3,6-dioxaoctane-1,8-diyldioxy)diphenolato
      kappa(2)O,O'](nitrato-kappa(2)O,O')dioxouranium(VI),
      (Et(3)NH)[UO(2)(H(2)O)L(NO(3))], which possesses a symmetry plane. The uranyl ion
      is coordinated to the two phenoxide O atoms, a nitrate ion and a water molecule
      (first sphere); the water molecule is itself held in the crown ether chain by
      hydrogen-bonding interactions, thus ensuring second-sphere coordination by the
      ligand L.

PMID- 11828090
TI  - 1'-Acetylferrocene-1-carboxylic acid: an instance of hydrogen bonding in the rare
      dimeric acid-to-ketone mode.
AB  - The title compound, [Fe(C(6)H(5)O(2))(C(7)H(7)O)], adopts a conformation
      involving partial staggering of its rings and aggregates in the solid as acid-to
      ketone hydrogen-bonding dimers [O.O = 2.720(4)A and O-H...O = 164 degree] having
      centrosymmetrically related components. Close intermolecular C-H...O contacts
      were found to both carboxyl O atoms.

PMID- 11828089
TI  - Bis(ethylenediamine)copper(II) bis(O,O'-diethyl dithiophosphate).
AB  - In the structure of the title compound, [Cu(II)(en)(2)][(EtO)(2)P(S)S](2) (en is
      ethylenediamine) or [Cu(C(2)H(8)N(2))(2)](C(4)H(10)O(2)PS(2))(2), the Cu atom
      lies on a center of inversion and is coordinated in a slightly distorted square
      coordination geometry by four N atoms from two ethylenediamine molecules. The
      diethyl dithiophosphate moieties, (EtO)(2)P(S)S(-), act as counter-anions.

PMID- 11828091
TI  - New girdle-like Mo18 polyanions linked into chains.
AB  - From the reduction of heptamolybdate, a polyoxomolybdate was obtained with the
      formula [Na(6)(+)(H(2)O)(16)(NH(2)CH(2)COO)(2)(
      )](4+).[Na(+)[H(9)Mo(10)(VI)Mo(8)(V)O(56)(NH(2)CH(2)COO)(2)(-)](5-)](4-).20H(2)O,
      i.e. heptasodium nonahydrogen tetracarbamate
      hexadecaaquahexapentacontaoxaoctadecamolybdate(V,VI) icosahydrate. The 18 Mo
      atoms are connected by bridging O atoms to form a centrosymmetric girdle-like
      structure, in which Mo(V)-Mo(V) units are found. An Na(+) cation occupies the
      central hole of the girdle, while four Na(+) cations are bonded to the O atoms on
      the girdle edge. The girdles are linked into a one-dimensional chain by the other
      Na(+) cations.

PMID- 11828092
TI  - Bis(mu-N,N-dimethyldithiocarbamato-kappa3S,S':S')bis[(dimethoxyphenylphosphane
      kappaP)(N,N-dimethyldithiocarbamato-kappa2S,S')cobalt(III)]
      bis(hexafluorophosphate).
AB  - Purple prismatic crystals of the title compound,
      [Co(2)(C(3)H(6)NS(2))(4)(C(8)H(11)O(2)P)(2)](PF(6))(2), were obtained by repeated
      recrystallization of trans-[Co(C(3)H(6)NS(2))(2)-(C(8)H(11)O(2)P)(2)]PF(6) from
      CH(3)CN/Et(2)O and then from MeOH/CH(2)Cl(2); during recrystallization one of the
      P(OMe)(2)Ph ligands was dissociated from the Co(III) center and the resulting
      Co(III) complex fragment underwent dimerization. The complex cation has a
      dinuclear structure bridged by one S atom of each of two of the N,N
      dimethyldithiocarbamate ligands, and has crystallographically imposed C(2)
      symmetry. Two P(OMe)(2)Ph ligands are coordinated at the transoid positions of
      the Co(2)(mu-C(3)H(6)NS(2))(2)(C(3)H(6)NS(2))(2) moiety, with Co-P bond lengths
      of 2.1921(11)A.

PMID- 11828093
TI  - An ion pair formed by protonated Fe(cp*py)2 and the octanuclear cluster
      U8Cl24O4(cp*py)2 [cp*py is tetramethyl-5-(2-pyridyl)cyclopentadiene].
AB  - In bis[1,1',2,2',3,3',4,4'-octamethyl-5-(2-pyridinio)-5'-(2-pyridyl)ferrocene] di
      mu(3)-chloro-hexadeca-mu(2)-chloro-hexachlorodi-mu(4)-oxo-di-mu(3)-oxo
      bis[(eta(5),kappaN)-1,2,3,4-tetramethyl-5-(2
      pyridyl)cyclopentadienyl]octauranium(IV) dichloromethane tetrasolvate,
      [Fe(C(14)H(17)N)(C(14)H(16)N)](2)[U(8)Cl(24)O(4)(C(14)H(16)N)(2)].4CH(2)Cl(2),
      (I), two protonated Fe(cp*py)(2) units [cp*py is tetramethyl-5-(2
      pyridyl)cyclopentadiene] form an ion pair with the dianionic centrosymmetric
      cluster U(8)Cl(24)O(4)(cp*py)(2). The latter is the highest nuclearity assemblage
      in the chemistry of uranium (non-uranyl) compounds reported to date.

PMID- 11828094
TI  - Tetrakis(dimethyl sulfide)palladium(II) bis(tetrafluoroborate) and tetrakis(1,4
      oxathiane-kappaS)palladium(II) bis(tetrafluoroborate).
AB  - Tetrakis(dimethyl sulfide)palladium(II) bis(tetrafluoroborate),
      [Pd(C(2)H(6)S)(4)](BF(4))(2), (I), and tetrakis(1,4-oxathiane
      kappaS)palladium(II) bis(tetrafluoroborate), [Pd(C(4)H(8)OS)(4)](BF(4))(2), (II),
      both crystallize as mononuclear square-planar complexes with tetrafluoroborate as
      the counter-ions. The Pd atom accepts four S-donor atoms and is positioned at an
      inversion centre in both compounds. The two unique S atoms in the dimethyl
      sulfide complex, (I), are disordered. The Pd-S distances are in the range
      2.3338(12)-2.3375(12)A in (I), and the corresponding distances in the thioxane
      complex, (II), are 2.3293(17) and 2.3406(17)A. The anions in both compounds
      interact weakly with the Pd atom.

PMID- 11828095
TI  - Bis(tetra-n-butylammonium) (a redetermination at 150K) and
      bis(tetraphenylarsonium) bis(1,3-dithiole-2-thione-4,5-dithiolato)zinc(II) (at
      300K).
AB  - The title compounds are salts of the general form (Q(+))(2)[Zn(dmit)(2)](2-),
      where dmit corresponds to the ligand (C(3)S(5))(-) present in both and Q(+) to
      the counter-cations ((n)Bu(4)N)(+) [or C(16)H(36)N(+)] and (Ph(4)As)(+) [or
      C(24)H(20)As(+)], respectively. In the first case, Zn is in the 4e special
      positions of space group C2/c and hence the [Zn(dmit)(2)](2-) dianion possesses
      twofold axial crystallographic symmetry. Including these, there are now 11 known
      examples of [Zn(dmit)(2)](2-) or its analogues, with O replacing the exocyclic
      thione S, and [Zn(dmio)(2)](2-) dianions in nine structures with various Q.
      Comparison of these reveals a remarkable variation in details of the conformation
      which the dianion may adopt in terms of Zn coordination, equivalence of the Zn-S
      bond lengths, displacement of Zn from the plane of the ligand and overall dianion
      shape.

PMID- 11828096
TI  - [2,6-Bis(isopropylthiomethyl)phenyl-kappa3S,C1,S']bromopalladium(II).
AB  - The title compound, [PdBr(C(14)H(21)S(2))] or [PdBr[C(6)H(3)(CH(2)S(i)Pr)(2)
      2,6]], exhibits square-planar geometry at the Pd centre, with three atoms of the
      square plane provided by the rigid thiopincer ligand, i.e. 1,3
      bis(thiomethyl)benzene.

PMID- 11828097
TI  - Platinum complexes of oxopurines: cis-bis(theophyllinato
      N7)bis(triphenylphosphine)platinum(II) and cis-chloro(theobrominato
      N1)bis(triphenylphosphine)platinum(II) ethanol hemisolvate.
AB  - The syntheses and structures of two mixed-ligand complexes of platinum(II) with
      deprotonated oxopurine bases and triphenylphosphine are reported, namely the
      theophyllinate complex cis-bis(1,2,3,6-tetrahydro-1,3-dimethylpurine-2,6-dionato
      kappaN(7))bis(triphenylphosphine-kappaP)platinum(II),
      [Pt(C(7)H(7)N(4)O(2))(2)(C(18)H(15)P)(2)], (I), and the theobrominate complex cis
      chloro(1,2,3,6-tetrahydro-3,7-dimethylpurine-2,6-dionato
      kappaN(1))bis(triphenylphosphine-kappaP)platinum(II) ethanol hemisolvate,
      [PtCl(C(7)H(7)N(4)O(2))(C(18)H(15)P)(2)].0.5C(2)H(5)OH, (II). In (I), the
      coordination geometry of Pt is square planar, formed by the two coordinating N
      atoms of the theophyllinate anions in a cis arrangement and two P atoms from the
      triphenylphosphine groups. In (II), there are two crystallographically
      independent molecules. They both exhibit a square-planar coordination geometry
      around Pt involving one Cl atom, the coordinating N atom of the theobrominate
      anion and two P atoms from the triphenylphosphine groups. The two
      triphenylphosphine groups are arranged in a cis configuration in both structures.
      The heterocyclic rings are rotated with respect to the coordination plane of the
      metal by 82.99(8) and 88.09(8) degree in complex (I), and by 85.91(16) and
      88.14(18) degree in complex (II). Both structures are stabilized by
      intramolecular stacking interactions involving the purine rings and the phenyl
      rings of adjacent triphenylphosphine moieties.

PMID- 11828098
TI  - [Mu-1kappa2O,O':2(eta5)-Cyclopentadienylcarboxylato][2(eta5)
      diphenylphosphinocyclopentadienyl]bis[1,1(eta5)
      tetramethylcyclopentadienyl]iron(II)titanium(III).
AB  - Reacting stoichiometric amounts of 1-(diphenylphosphino)ferrocenecarboxylic acid
      and [Ti(eta(5)-C(5)HMe(4))(2)(eta(2)-Me(3)SiC[triple-bond]CSiMe(3))] produced the
      title carboxylatotitanocene complex, [[mu-1kappa(2)O,O':2(eta(5))
      C(5)H(4)CO(2)][2(eta(5))-C(5)H(4)P(C(6)H(5))(2)][1(eta(5))
      C(5)H(CH(3))(4)](2)Fe(II)Ti(III)] or
      [FeTi(C(9)H(13))(2)(C(6)H(4)O(2))(C(17)H(14)P)]. The angle subtended by the
      Ti/O/O' plane, where O and O' are the donor atoms of the kappa(2)-carboxylate
      group, and the plane of the carboxyl-substituted ferrocene cyclopentadienyl is
      24.93(6) degree.

PMID- 11828099
TI  - [(1,4,8,11-Tetraazacyclotetradeca-1,4,8,11-tetrayl)tetraacetamide
      kappa6N1,N4,N8,N11,O1,O8]copper(II) sulfate 4.5-hydrate.
AB  - The crystal structure of the title copper(II) complex,
      [Cu(C(18)H(36)N(8)O(4))]SO(4).4.5H(2)O, formed with the tetraamide cyclam
      derivative 2-(4,8,11-triscarbamoylmethyl-1,4,8,11-tetraazacyclotetradec-1
      yl)acetamide (TETAM), is described. The macrocycle lies on an inversion centre
      occupied by the hexacoordinated Cu atom. The four macrocyclic tertiary amines
      form the equatorial plane of an axially Jahn-Teller elongated octahedron. Two O
      atoms belonging to two diagonally opposite amide groups occupy the apical
      positions, giving rise to a trans-III stereochemistry, while both the remaining
      pendant side arms extend outwards from the macrocyclic cavity and are engaged in
      hydrogen bonds with sulfate anions and co-crystallized water molecules.

PMID- 11828100
TI  - Dichlorobis(trimethylenethiourea-kappaS)antimony(III) chloride.
AB  - In the title compound, [SbCl(2)(C(4)H(8)N(2)S)(2)]Cl, the coordination around the
      Sb atom can be described as distorted pseudo-octahedral. Both rings of the
      trimethylenethiourea ligands [alternatively 3,4,5,6-tetrahydropyrimidine-2(1H)
      thione] adopt an envelope conformation. The molecules are connected into dimers
      in the ab plane by two intermolecular hydrogen bonds. The dimers are arranged
      into infinite one-dimensional chains along the a axis as a result of the Cl(-)
      ions forming intermolecular hydrogen bonds with three NH groups.

PMID- 11828101
TI  - catena-Poly[[dicyanamido(5,5'-dimethyl-2,2'-bipyridine-kappa2N,N')copper(II)]-mu
      dicyanamido-kappa2N1:N5].
AB  - In the crystal structure of the title compound,
      [Cu(C(2)N(3))(2)(C(12)H(12)N(2))](n), the Cu(II) atom adopts a distorted square
      pyramidal geometry, the basal plane of which is formed by two N atoms of the
      bipyridine ligand, one N atom of a bidentate dicyanamide anion and one N atom of
      a monodentate dicyanamide anion [Cu-N = 1.9760(15)-2.0157(15)A]. The apical
      position is occupied by an N atom of a bidentate dicyanamide anion, located
      2.2468(16)A from the Cu atom, thus forming a one-dimensional polymeric chain.

PMID- 11828102
TI  - (2-Thienylmethyl)ammonium trichlorostannate(II): a hybrid salt.
AB  - The structure of the title hybrid salt, (C(5)H(8)NS)[SnCl(3)], is built up from
      segregated layers of organic cations and Sn polyhedra. [SnCl(3)](-) groups are
      linked together by weak Sn...Cl interactions to form a one-dimensional polymeric
      chain of anions.

PMID- 11828103
TI  - Isomorphism and phase transition in triferrocenylboroxine and
      triferrocenylborazine.
AB  - The crystal structures of triferrocenylboroxine,
      [Fe(3)(C(5)H(5))(3)(C(15)H(12)B(3)O(3))], (I), and triferrocenylborazine,
      [Fe(3)(C(5)H(5))(3)(C(15)H(15)B(3)N(3))], (II), are isomorphous. At room
      temperature, the space group is Cmc2(1) and the molecules have crystallographic m
      symmetry. A reversible phase transition occurs at 283(2)K for (I) and at 263(5)K
      for (II). In the low-temperature phase, the space group of both compounds is
      P2(1) and the molecules no longer have internal symmetry. Intermolecular C-H...pi
      interactions are enhanced in the low-temperature phase.

PMID- 11828104
TI  - Bis[mu-4-(ethylammoniomethyl)-3,5-dimethylpyrazolato-kappa2N1:N2]bis[(eta4-1,5
      cyclooctadiene)rhodium(I)] dichloride dichloromethane methanol solvate.
AB  - In the title compound,
      [Rh(2)(C(8)H(15)N(3))(2)(C(8)H(12))(2)]Cl(2).CH(2)Cl(2).CH(3)OH, the dinuclear
      Rh(I) complex has C(2) symmetry and the two pyrazolato ligands act as mu-bridges.
      The coordination of each Rh(I) cation is completed by one cyclooctadiene (COD)
      ligand. It is shown that the average Rh-C(COD) distance is linearly dependent on
      the Rh-N(pyrazole) distance in this type of compound, and this is ascribed to the
      steric hindrance produced by the packing.

PMID- 11828105
TI  - Diaquabis[mu-(R,R)-tartrato-kappa4O1,O2:O3,O4]dinickel(II) trihydrate.
AB  - In the crystal structure of the title compound,
      [Ni(2)(C(4)H(4)O(6))(2)(H(2)O)(2)].3H(2)O, two nickel cations, two tartrate
      anions and two water molecules form the dimeric complex. Each nickel cation is in
      a distorted octahedral environment composed of four O atoms of two
      crystallographically independent tartrate anions, one water molecule and one O
      atom of a symmetry-equivalent tartrate anion. The asymmetric unit contains three
      additional water molecules which are connected via hydrogen bonding.

PMID- 11828106
TI  - Bis[[mu-N,N'-bis(salicylidene)-1,4-butanediamine-N,N',O,O'-copper(II)]-mu-chloro
      chloromercury(II)].
AB  - A new tetranuclear Cu(II)-Hg(II)-Hg(II)-Cu(II) complex,
      [Cu(2)Hg(2)Cl(4)(C(18)H(18)N(2)O(2))(2)], has been prepared by means of a copper
      complex found in the literature. The molecular structure of this complex was
      determined by X-ray diffraction and the Cu-Hg-Hg-Cu chain was seen to be non
      linear. The change in magnetic susceptibility with temperature was recorded for
      this complex and observed to abide by the Curie-Weiss law. The coordination
      around the Hg(II) ions is square pyramidal. The Cu...Hg bridging distance is
      3.5269(7)A.

PMID- 11828107
TI  - Ethyl (6aRS,8RS,12bRS)-6-oxo-8-phenyl-6a,7,8,12b-tetrahydro-6H
      benzo[b]naphtho[1,2-d]pyran-6a-carboxylate.
AB  - In the title compound, C(26)H(22)O(4), the pyranone ring adopts a twisted boat
      conformation, while the cyclohexane ring is close to an envelope conformation.
      The dihedral angle between the mean planes of the coumarin and naphthalene
      systems is 78.8(1) degree. The attached phenyl ring is in an equatorial position
      with respect to the cyclohexane ring.

PMID- 11828108
TI  - Syn- and anticlinal isomers of 2a'-acetoxy-1,7'-diacetyl-7',7a'-dihydro-2
      oxospiro[1H-indole-3(2H),2'(2a'H)-oxeto[3,2-b]indole].
AB  - In the syn- and anticlinal isomers of the title compound, C(22)H(18)N(2)O(6), the
      indole moiety is not completely planar, with the pyrrolidine ring being distorted
      very slightly towards a conformation intermediate between half-chair and
      envelope. The molecular and packing structures in the crystals of these isomers
      are stabilized by C-H...O interactions.

PMID- 11828109
TI  - D-Secoestrone derivatives. V1. 3-Methoxy-17-oxo-17-phenyl-16,17-secoestra
      1,3,5(10)-triene-16-nitrile and 17-hydroxy-3-methoxy-17-phenyl-16,17-secoestra
      1,3,5(10)-triene-16-nitrile.
AB  - The two title 16,17-secoestrone derivatives, 3-methoxy-17-oxo-17-phenyl-16,17
      secoestra-1,3,5(10)-triene-16-nitrile, C(25)H(27)NO(2), (I) (17-oxo substituent),
      and 17-hydroxy-3-methoxy-17-phenyl-16,17-secoestra-1,3,5(10)-triene-16-nitrile,
      C(25)H(29)NO(2), (II) (17-hydroxy substituent), have quite different
      conformations in the solid state. These conformational differences can be
      minimized by molecular mechanics calculations. Thus, the remarkable difference in
      the biological activity of the two compounds, e.g. the strong oestrogenic
      characteristics of (I) and the moderate antioestrogenic action of (II), must be
      caused by the difference in substitution at C17. In (II), the molecules are
      linked by O-H...N hydrogen bonds, forming spirals along the b direction.

PMID- 11828110
TI  - 4-(Trifluoromethyl)benzonitrile.
AB  - 4-(Trifluoromethyl)benzonitrile, C(8)H(4)F(3)N, at 123K contains molecules linked
      together through one C-H...F bond and two C-H...N hydrogen bonds into sheets that
      are further crosslinked to form a dense two-dimensional network without pi...pi
      ring interactions. The aromatic ring is slightly deformed due to the two para
      related electronegative groups.

PMID- 11828111
TI  - 4-Methyl-2-[N-(3,4-methylenedioxybenzylidene)hydrazino]thiazole and its reduction
      product, 4-methyl-2-[N-(3,4-methylenedioxybenzylidene)hydrazono]-4,5
      dihydrothiazole.
AB  - The crystal structures of 4-methyl-2-[N-(3,4
      methylenedioxybenzylidene)hydrazino]thiazole, C(12)H(11)N(3)O(2)S, and its
      reduction product 4-methyl-2-[N-(3,4-methylenedioxybenzylidene)hydrazono]-4,5
      dihydrothiazole, C(12)H(13)N(3)O(2)S, have been determined and compared. In the
      reduction product, the tautomer observed bears an H atom on the exocyclic N atom.
      Both compounds form hydrogen-bonded dimers over centers of inversion.

PMID- 11828112
TI  - Three polar derivatives of N-ethylcarbazole: materials for optical applications.
AB  - Three N-ethylcarbazole derivatives have been synthesized and tested for non
      linear optical (NLO) properties. The compounds are 2-(9-ethyl-9H-carbazol-3
      ylmethylene)malononitrile, C(18)H(13)N(3), (IIIa), 2-cyano-3-(9-ethyl-9H-carbazol
      3-yl)thioacrylamide, C(18)H(15)N(3)S, (IIIb), and 3-(9-ethyl-9H-carbazol-3-yl)-2
      (4-phenyl-1,3-thiazol-2-yl)acrylonitrile, C(26)H(19)N(3)S, (V). It was found that
      the molecules of (IIIa) and (V) are nearly planar, while non-planarity is more
      pronounced for (IIIb). Molecules of (IIIa) and (V) exhibit herring-bone packing
      motifs. In (IIIb), the molecules form layers coplanar with (-201), within which
      they form centrosymmetric dimers via N-H...S hydrogen bonds.

PMID- 11828113
TI  - Methyl 3-(4-methoxyphenyl)prop-2-enoate.
AB  - The title molecule, C(11)H(12)O(3), is almost planar, with an average deviation
      of the C and O atoms from the least-squares plane of 0.146(4)A. The geometry
      about the C=C bond is trans. The phenyl ring and -COOCH(3) group are twisted with
      respect to the double bond by 9.3(3) and 5.6(5) degree, respectively. The
      endocyclic angle at the junction of the propenoate group and the phenyl ring is
      decreased from 120 degree by 2.6(2) degree, whereas two neighbouring angles
      around the ring are increased by 2.3(2) and 0.9(2) degree. This is probably
      associated with the charge-transfer interaction of the phenyl ring and -COOCH(3)
      group through the C=C double bond. The molecules are joined together through C
      H...O hydrogen bonds between the methoxy and ester groups to form characteristic
      zigzag chains extended along the c axis.

PMID- 11828114
TI  - 6-Aminopyridine-3-thiol.
AB  - The title compound, C(5)H(6)N(2)S, is a simple but novel pyridinethiol of
      pharmacological interest. The molecule is planar. The crystal packing is
      dominated by hydrophobic contacts and a pair of hydrogen-bond interactions
      between the amino group of one pyridine molecule and the ring N atom of a
      neighbouring base, stabilizing the structure.

PMID- 11828115
TI  - 6-Propylamino-2,6-propylepimino-2,4,4,8,8-pentakis(pyrrolidin-1-yl)
      1,3,5,7,2lambda5,4lambda5,6lambda5,8lambda5-tetraazatetraphosphorocine.
AB  - The title compound, C(26)H(55)N(11)P(4), consists of a bicyclic phosphazene ring
      with five bulky pyrrolidino and one propylamino group, together with a second
      propylamino group bridging the two P atoms. The asymmetric unit contains two
      molecules with very similar conformations. The bulky substituents are
      instrumental in determining the bicyclic P(4)N(5) ring conformation. Each of the
      fused six-membered N(3)P(3) rings is in a sofa conformation. The P-N distances in
      the bridge are non-equivalent and one of them is the longest P-N bond in the
      molecule. The hybridization of the bridging N atom is pyramidal. The single and
      double P-N bonds cannot easily be distinguished, since they retain their
      phosphazenic character in the phosphazene macro-rings.

PMID- 11828116
TI  - (-)-Dimenthyl malonate.
AB  - The title compound, bis(2-isopropyl-5-methylcyclohex-1-yl) malonate,
      C(23)H(40)O(4), crystallizes in the monoclinic space group P2(1). In the crystal,
      the molecule is not C(2) symmetric.

PMID- 11828117
TI  - 2,3,6,7-Tetrahydroxy-9,10-dimethyl-9,10-dihydro-9,10-ethanoanthracene bis(1,4
      dioxane) solvate.
AB  - 2,3,6,7-Tetrahydroxy-9,10-dimethyl-9,10-dihydro-9,10-ethanoanthracene
      crystallizes with 1,4-dioxane to give a bis-solvate,
      C(18)H(18)O(4).2C(4)H(8)O(2). The bis(catechol) molecule is located on a twofold
      axis and the two aromatic rings form a dihedral angle of 130.61(4) degree.
      Hydrogen bonds are formed between the hydroxyl groups and either a neighbouring
      bis(catechol) molecule or the ether-O atom of a dioxane molecule.

PMID- 11828118
TI  - N-(3-Phenoxy-4-pyridinio)methanesulfonamidate.
AB  - The title compound, C(12)H(12)N(2)O(3)S, is a strict pyridine analogue of
      nimesulide, a selective inhibitor of cyclooxygenase-2. The structure is
      characterized by a pyridinium ring with a deprotonated sulfonamide group. An
      intermolecular charge-assisted hydrogen bond between these two groups is observed
      within the crystal packing, linking the molecules into an infinite chain running
      along the b-axis direction.

PMID- 11828119
TI  - Stereochemistry of two new polyfunctionalized gem-dihalocyclopropanes.
AB  - The two new gem-dihalogenocyclopropanes (1'S,3R)-3-(2',2'-dichloro-1'
      methylcyclopropyl)-6-oxoheptanoic acid, C(11)H(16)Cl(2)O(3), (2), and (1'S,3R)-3
      (2',2'-dibromo-1'-methylcyclopropyl)-6-oxoheptanoic acid, C(11)H(16)Br(2)O(3),
      (3), are isostructural. Both present two stereogenic centers at C1' and C3. The
      absolute configuration was determined by X-ray methods. The cyclopropyl rings are
      unsymmetrical, the shortest bond being distal with respect to the alkyl
      substituted C atom.

PMID- 11828120
TI  - cis- and trans-2-(4-tert-Butylcyclohexyloxy)-1,3,5-trinitrobenzene.
AB  - The structures of cis- and trans-2-(4-tert-butylcyclohexyloxy)-1,3,5
      trinitrobenzene, C(16)H(21)N(3)O(7), (I) and (II), respectively, were determined
      at low temperature in order to obtain accurate structural parameters for
      comparison purposes. The C(alkyl)-O(ether) bond distances are 1.497(2) and
      1.491(2)A for (I) and (II), respectively.

PMID- 11828122
TI  - Hydrogen bonding in C-substituted nitroanilines: sheets built from alternating
      R(2)(2)(12) and R(6)(6)(36) rings in 2-bromo-6-cyano-4-nitroaniline.
AB  - Molecules of the title compound (systematic name: 2-amino-3-bromo-5
      nitrobenzonitrile), C(7)H(4)BrN(3)O(2), are linked by N-H...N and N-H...O
      hydrogen bonds [H...N 2.19A, N...N 3.019(4)A and N-H...N 157 degree, and H...O
      2.17A, N...O 2.854(3)A and N-H...O 134 degree] to form (10-3) sheets built from
      alternating R(2)(2)(12) and R(6)(6)(36) rings, both of which are centrosymmetric.

PMID- 11828121
TI  - Hydrogen bonding in C-substituted nitroanilines: molecular ladders in 2
      trifluoromethyl-4-nitroaniline and sheets of R(4)(4)(12) and R(4)(4)(32) rings in
      3-trifluoromethyl-4-nitroaniline.
AB  - In 2-trifluoromethyl-4-nitroaniline, C(7)H(5)F(3)N(2)O(2), (I), the molecules lie
      across a mirror plane in space group Pnma. The molecules are linked by paired N
      H...O hydrogen bonds to form a C(8)[R(2)(2)(6)] chain of rings, pairs of which
      are linked into a molecular ladder by a single C-H...O hydrogen bond. The
      isomeric 3-trifluoromethyl-4-nitroaniline, (II), has Z' = 2 in space group
      P2(1)/c. Each molecule is linked to four others by N-H...O hydrogen bonds to form
      sheets built from alternating R(4)(4)(12) and R(4)(4)(32) rings.

PMID- 11828124
TI  - (1R,3S)-Camphoramic acid.
AB  - The title chiral compound, 3-aminocarbonyl-1,2,2-trimethylcyclopentane-1
      carboxylic acid, C(10)H(17)NO(3), was prepared from (1R,3S)-camphoric acid. The
      five-membered ring adopts a conformation which is intermediate between a twist
      and an envelope. Elongations of the C-C bonds and contractions of the C-C-C bond
      angles are observed within the five-membered ring. A (1)H NMR spectrum was
      recorded to assist in distinguishing the amide group from the carboxyl group.

PMID- 11828123
TI  - Supramolecular hydrogen-bonded hexamers in two 5-aryl-3-methyl-1-phenyl-1,6,7,8
      tetrahydropyrazolo[3,4-b][1,4]diazepines.
AB  - In both title compounds, i.e. 3-methyl-1,5-diphenyl-1,6,7,8
      tetrahydropyrazolo[3,4-b][1,4]diazepine, C(19)H(18)N(4), (I), and 5-(4
      chlorophenyl)-3-methyl-1-phenyl-1,6,7,8-tetrahydropyrazolo[3,4-b][1,4]diazepine,
      C(19)H(17)ClN(4), (II), an N-H...N hydrogen bond links six molecules to form an
      R(6)(6)(30) ring. Compound (I) crystallizes in the R3 space group and (II)
      crystallizes in P1 with three molecules in the asymmetric unit. The molecule of
      (I) contains a disordered seven-membered ring.

PMID- 11828125
TI  - New electron-deficient chiral phosphines: (4R,5R)-1,3
      bis(trifluoromethanesulfonyl)perhydro-1,3,2-benzodiazaphosphol-2-yl] substituted
      amines.
AB  - Three chiral electron-deficient phosphine ligands, [(4R,15R)-,3
      bis(trifluoromethanesulfonyl)perhydro-1,3,2-benzodiazaphosphol-2-yl]diethylamine,
      C(12)H(20)F(6)N(3)O(4)PS(2), (IIIa), [(4R,5R)-1,3
      bis(trifluoromethanesulfonyl)perhydro-1,3,2-benzodiazaphosphol-2
      yl]dimethylamine, C(10)H(16)F(6)N(3)O(4)PS(2), (IIIb), and bis[(4R,5R)-1,3
      bis(trifluoromethanesulfonyl)perhydro-1,3,2-benzodiazaphosphol-2-yl]methylamine,
      (IV), as the chloroform solvate, C(17)H(23)F(12)N(5)O(8)P(2)S(4).0.98CHCl(3),
      have been prepared from (1R,2R)-N,N'-bis(trifluoromethanesulfonyl)-1,2
      cyclohexanediamine and diethyl phosphoramidous dichloride, dimethyl
      phosphoramidous dichloride or methyl imidodiphosphorus tetrachloride. The pi
      acceptor abilities of these new types of ligands have been evaluated by X-ray
      determination of the P-N bond lengths; it has been found that the most promising
      ligand is the bis(phosphine) (IV).

PMID- 11828126
TI  - Melaminium acetate acetic acid solvate monohydrate.
AB  - The crystals of the title new melaminium salt, 2,4,6-triamino-1,3,5-triazin-1-ium
      acetate acetic acid solvate monohydrate, C(3)H(7)N(6)(+).CH(3)COO(
      ).CH(3)COOH.H(2)O, are built up from singly protonated melaminium residues,
      acetate anions, and acetic acid and water molecules. The melaminium residues are
      interconnected by N-H...N hydrogen bonds to form chains along the [010]
      direction. These chains of melaminium residues form stacks aligned along the a
      axis. The acetic acid molecules interact with the acetate anions via the H atom
      of their carboxylic acid groups and, together with the water molecules, form
      layers that are parallel to the (001) plane. The oppositely charged moieties
      interact via multiple N-H...O hydrogen bonds that stabilize a pseudo-two
      dimensional stacking structure.

PMID- 11828127
TI  - Redetermination of the twinned structure of triacetone amine monohydrate.
AB  - The structure of triacetone amine monohydrate (systematic name: 2,2,6,6
      tetramethylpiperidin-4-one monohydrate), C(9)H(17)NO.H(2)O, has been redetermined
      at 180K. The compound crystallizes in space group P2(1)/c with a monoclinic angle
      of 90.084(3) degree. All crystals examined exhibited twinning and appeared
      orthorhombic, with a unit-cell volume half that of the true volume.

PMID- 11828128
TI  - (Z)-2-Methylbuten-1-yl(aryl)iodonium trifluoromethanesulfonates containing
      electron-withdrawing groups on the aryl moiety.
AB  - The crystal structures of [(Z)-2-methylbut-1-en-1-yl][4
      (trifluoromethyl)phenyl]iodonium trifluoromethanesulfonate,
      C(12)H(13)F(3)I(+).CF(3)O(3)S(-), (I), (3,5-dichlorophenyl)[(Z)-2-methylbut-1-en
      1-yl]iodonium trifluoromethanesulfonate, C(11)H(12)Cl(2)I(+).CF(3)O(3)S(-), (II),
      and bis[[3,5-bis(trifluoromethyl)phenyl][(Z)-2-methylbut-1-en-1-yl]iodonium]
      bis(trifluoromethanesulfonate) dichloromethane solvate,
      2C(13)H(12)F(6)I(+).2CF(3)O(3)S(-).CH(2)Cl(2), (III), are described. Neither
      simple acyclic beta,beta-dialkyl-substituted alkenyl(aryl)idonium salts nor a
      series containing electron-deficient aryl rings have been described prior to this
      work. Compounds (I)-(III) were found to have distorted square-planar geometries,
      with each I atom interacting with two trifluoromethanesulfonate counter-ions.

PMID- 11828129
TI  - 2-(4-Chlorophenyl)-1,3-dicyano-6,7-dihydro-4-imino-9,10
      dimethoxybenzo[a]quinolizine-water (2/5).
AB  - Crystals of the title compound, C(23)H(17)ClN(4)O(2).2.5H(2)O, contain channels
      filled with highly disordered water molecules. The best structure refinement was
      obtained by removing the solvent contribution from the intensity data and
      refining against a solvent-free model. The central six-membered ring of the
      quinolizine molecule has a slightly distorted screw-boat conformation.

PMID- 11828130
TI  - 2-(4-Bromophenyl)-1,2-dihydropyrimido[1,2-a]benzimidazol-4(3H)-one and 4-(4
      methylphenyl)-3,4-dihydropyrimido[1,2-a]benzimidazol-2(1H)-one form hydrogen
      bonded base-paired dimers.
AB  - The title compounds, 2-(4-bromophenyl)-1,2-dihydropyrimido[1,2-a]benzimidazol-4
      (3H)-one, C(16)H(12)BrN(3)O, (IVa), and 4-(4-methylphenyl)-3,4
      dihydropyrimido[1,2-a]benzimidazol-2-(1H)-one, C(17)H(15)N(3)O, (Vb), both form
      R(2)(2)(8) centrosymmetric dimers via N-H...N hydrogen bonds. The N...N distance
      is 2.943(3)A for (IVa) and 2.8481(16)A for (Vb), with the corresponding N-H...N
      angles being 129 and 167 degree, respectively. However, in other respects, the
      supramolecular structures of the two compounds differ. Both compounds contain
      different C-H...pi interactions, in which the C-H...pi(centroid) distances are
      2.59 and 2.47A for (IVa) and (Vb), respectively (the latter being a short
      distance), with C-H...pi(centroid) angles of 158 and 159 degree, respectively.
      The supramolecular structures also differ, with a short Br...O distance of
      3.117(2)A in bromo derivative (IVa), and a C-H...O interaction with a C...O
      distance of 3.2561(19)A and a C-H...O angle of 127 degree in tolyl system (Vb).
      The dihydropyrimido part of (Vb) is disordered, with a ratio of the major and
      minor components of 0.9:0.1. The disorder consists of two non-interchangeable
      envelope conformers, each with an equatorial tolyl group and an axial methine H
      atom.

PMID- 11828131
TI  - Monitoring of quality of life in congestive heart failure populations.
AB  - The health care system has traditionally focused on treating disease at the point
      of failure, such as life-saving surgery or intensive medical therapy. As
      demographics shift more to an aging population, management of health-related
      quality of life and life-restricting disease becomes more necessary. Prominent
      among such diseases is congestive heart failure, which must be addressed as a
      major chronic health condition with its consequent effect on quality of life.
      This paper examines the methods of monitoring the quality of life in congestive
      heart failure. Particular attention is paid to congestive heart failure-related
      questionnaires to derive lifestyle information directly from patients. Comparison
      is made with general quality of life instruments. Most commonly, these
      questionnaires are applied to small populations in limited situations. New
      technology, such as the Internet, has greatly expanded the breadth and depth of
      health monitors by tracking status directly in patients' homes. This promises new
      levels of population management for heart disease. (c)2001 by CHF, Inc.

PMID- 11828132
TI  - Atrial fibrillation in patients with heart failure: pharmacologic options.
AB  - Atrial fibrillation is a common arrhythmia in patients with heart failure. The
      presence of atrial fibrillation deteriorates cardiac function and increases the
      risk of thromboembolic events. The management of patients with atrial
      fibrillation in association with heart failure should consist of ventricular rate
      control, prevention of thromboembolic events, and conversion to normal sinus
      rhythm. Traditionally, digoxin has been widely used in patients with heart
      failure and atrial fibrillation; however, it does very little to restore sinus
      rhythm and requires the addition of another rate-limiting agent to control
      ventricular rate. The likelihood of successful cardioversion is dependent on the
      duration of heart failure and the degree of neurohormonal activation. The
      initiation of antiarrhythmic drug therapy in patients with heart failure should
      be guided by safety issues as well as consideration of potential benefits vs.
      risks associated with therapy. Amiodarone has been evaluated in numerous clinical
      trials and appears to be safe and effective when used in low dosage. Treatment
      with dofetilide is another option. Comparative studies with oral dofetilide vs.
      amiodarone are needed to evaluate their efficacy in restoration and maintenance
      of sinus rhythm in patients with heart failure. Such trials will clearly define
      the role of dofetilide in the treatment of atrial fibrillation. Routine
      prophylactic use of antiarrhythmic drug therapy for chronic atrial fibrillation
      in the setting of heart failure is not recommended due to a low efficacy rate and
      high proarrhythmic risk. Anticoagulation with warfarin and rate control remain
      the standard therapy. (c)2001 by CHF, Inc.

PMID- 11828133
TI  - Value of dobutamine echocardiography for the assessment of myocardial viability
      for revascularization.
AB  - Coronary artery disease accounts for a majority of heart failure cases in the
      western world. Many cardiologists believe that abnormal regional contractions in
      patients with coronary artery disease is equivalent to irreversibly damaged
      myocardium. Studies now challenge this long-held assumption. Data exist regarding
      the value of assessing myocardial viability in those patients with severe left
      ventricular dysfunction and coronary artery disease. This report discusses
      dobutamine echocardiography as a technique for assessing myocardial viability and
      for selecting patients for revascularization. (c)2001 by CHF, Inc.

PMID- 11828134
TI  - Use of a clinical care map for the management of congestive heart failure in a
      community hospital.
AB  - BACKGROUND. Managed care rewards those individuals and institutions capable of
      achieving superior patient outcomes while making wise use of limited resources.
      However, studies of patient outcomes under these circumstances are lacking. We
      sought to investigate whether decreasing length of stay and limiting resource
      utilization had a negative effect on objective measurements of patient outcome
      for patients with congestive heart failure. METHODS. Guided by studies of
      evidence-based medicine, a multidisciplinary team developed and implemented a
      clinical care multidisciplinary action plan for the inpatient management of
      congestive heart failure. This provided practitioners with a target length of
      hospital stay, projections for daily improvements based on intervention,
      guidelines for diagnostic studies and medical therapy, early identification of
      patients with special discharge needs, and intensive patient education. RESULTS.
      Shorter lengths of stay for patients with congestive heart failure were achieved
      without negatively impacting on mortality or readmission rates. The study found a
      trend in favor of greater utilization of appropriate medical therapy despite
      shorter hospitalization. CONCLUSION. The use of a clinical care map for
      management of complex medical illnesses can be associated with shorter hospital
      stay without sacrificing patient outcomes. (c)2001 by CHF, Inc.

PMID- 11828135
TI  - Nonadherence with ACE inhibitors is common and can be detected in clinical
      practice by routine serum ACE activity.
AB  - Our objective was to assess whether serum angiotensin-converting enzyme (ACE)
      activity during routine clinical practice accurately reflects patient adherence
      to ACE inhibitor treatment in chronic heart failure (CHF). During 1994-95, ACE
      was measured in 73 CHF patients who were routinely attending the heart failure
      clinic at Ninewells Hospital. At the same time, the Medicines Monitoring Unit
      collected data on whether and when prescriptions for ACE inhibitors were redeemed
      at community pharmacies, which enabled each patient's adherence over a prolonged
      period to be assessed. We then correlated whether an elevation in serum ACE was
      associated with poor adherence with ACE inhibitor treatment. In total, 18% of CHF
      patients appeared to exhibit less than 70% adherence with their ACE inhibitor
      treatment, with 34% exhibiting less than 85%adherence and 58% exhibiting less
      than 100% adherence. A serum ACE activity of more than 12 U/L gave 91% positive
      predictive accuracy that the patient was less than 100% adherent with his or her
      ACE inhibitor treatment. At the other extreme, a serum ACE less than 6.5 U/L gave
      81% positive predictive accuracy that the patient was more than 85% adherent with
      ACE inhibitor treatment. Nonadherence with ACE inhibitor treatment, therefore,
      was found to be common in patients with CHF. The simple, inexpensive test of
      serum ACE activity can be used in CHF patients to identify many, although not
      all, nonadherent patients so that adherence-enhancing strategies can be targeted
      toward them. Further work is clearly required to explore the precise clinical
      utility of this promising test. (c)2001 by CHF, Inc.

PMID- 11828136
TI  - Successful weaning from milrinone of a patient with severe congestive heart
      failure using carvedilol.
AB  - Congestive heart failure is a major and growing health care concern worldwide,
      and mortality in patients with severe heart failure is high. Few options are
      available to patients with New York Heart Association class IV heart failure
      refractory to oral medical therapy. Over the last 15-20 years milrinone, a
      phosphodiesterase-III inhibitor, has been used occasionally to treat patients
      with acute heart failure and as a bridge to heart transplantation and, more
      recently, has been used intermittently or continuously on an outpatient basis. We
      report a patient with severe, chronic congestive heart failure, whom we treated
      successfully with continuous milrinone infusions as an outpatient. We were able
      to wean him of the milrinone after successful up-titration of carvedilol. Nine
      months after discontinuation of milrinone the patient remains stable in New York
      Heart Association class I on high dose carvedilol. Research is required to
      validate the possibility that patients with severe heart failure may be
      successfully weaned from milrinone using carvedilol and achieve significant
      improvement of their functional status and quality of life. This may prove to be
      an effective strategy for the treatment of selected patients with severe, chronic
      congestive heart failure. (c)2001 by CHF, Inc.

PMID- 11828137
TI  - Difficult cases in heart failure: Expanding the therapeutic armamentarium in
      decompensated heart failure: using intravenous fenoldopam.
AB  - The authors report the clinical use of fenoldopam, a dopamine agonist, in a
      patient with decompensated heart failure and severe pulmonary hypertension. In
      addition, they explore the potential mechanisms by which fenoldopam exerts its
      beneficial effects and review the literature regarding the use of this agent in
      systolic heart failure. (c)2001 by CHF, Inc.

PMID- 11828138
TI  - Baseline quality indicator rates from the National Heart Failure Project: a HCFA
      initiative to improve the care of medicare beneficiaries with heart failure.
AB  - This column is the third in a series reporting on Health Care Financing
      Administration (HCFA) initiatives to improve care for Medicare beneficiaries with
      heart failure. The first paper outlined the history of HCFA quality improvement
      projects and current initiatives to improve care in six priority areas: heart
      failure, acute myocardial infarction, stroke, pneumonia, diabetes, and breast
      cancer. The second reported in more detail the structure of the national
      inpatient fee-for-service heart failure initiative, known as the National Heart
      Failure project. It described the development of the quality indicators, the
      sampling strategy for selecting charts to be reviewed, and the types of local
      efforts spurred by the project through the activities of each state's HCFA
      contractor peer review organization. This article discusses baseline quality
      indicator rates from the National Heart Failure project. (c)2001 by CHF, Inc.

PMID- 11828139
TI  - Frontiers in congestive heart failure: Patient characteristics associated with
      care by a cardiologist among adults hospitalized with severe congestive heart
      failure.

PMID- 11828140
TI  - Frontiers in congestive heart failure: Antiremodeling effects on the left
      ventricle during beta-blockade with metoprolol in the treatment of chronic heart
      failure.

PMID- 11828141
TI  - Diastolic dysfunction in the presence of left ventricular systolic dysfunction:
      implications of beta-adrenergic blocking therapy.
AB  - The contribution of left ventricular diastolic dysfunction to the impairment in
      overall left ventricular performance in patients with systolic dysfunction is
      underappreciated. This article summarizes the available data on diastolic
      dysfunction in patients with congestive heart failure in which the predominant
      abnormality was thought to be left ventricular systolic dysfunction. The
      prevalence and identification of diastolic abnormalities and their clinical
      relevance are addressed, particularly the role of beta-adrenergic blocking
      therapy. The potential benefits of beta-adrenergic blocking therapy to diastolic
      performance are discussed from both a hemodynamic and clinical standpoint, with
      the implication that diastolic performance and its modulation should be
      considered in future investigations. (c)2001 by CHF, Inc.

PMID- 11828142
TI  - Nesiritide (hBNP): a new class of therapeutic peptide for the treatment of
      decompensated congestive heart failure.
AB  - Natriuretic peptides are a family of endogenous peptide hormones with
      vasodilating, natriuretic, diuretic, and lusitropic properties. Administration of
      pharmacologic doses of exogenous natriuretic peptides may provide therapeutic
      benefit in patients with chronic heart failure. In controlled clinical trials,
      short-term administration of nesiritide (human brain natriuretic peptide) to
      patients with heart failure is associated with improved resting hemodynamics,
      modest increases in sodium excretion, evidence of suppression of neurohormonal
      activation, and improvements in symptoms of heart failure. Additional trials to
      determine the clinical efficacy and safety of nesiritide are warranted. (c)2001
      by CHF, Inc.

PMID- 11828143
TI  - Peripartum cardiomyopathy: case report and literature review.
AB  - Peripartum cardiomyopathy is an unusual and uncommon form of dilated
      cardiomyopathy that is often fatal to young women. Fetal outcome, however, is
      quite good. The disease occurs in 250-1350 women each year in the United States.
      Myocarditis of viral, immunologic, or idiopathic etiology has been suggested.
      Diagnostic findings are consistent with congestive heart failure. Primary therapy
      consists of bed rest, sodium and fluid restriction, vasodilators, digoxin, and
      diuretics. Refractory cases can be treated with cardiac transplantation. Selected
      patients require anticoagulation. Prognosis depends on 6-month recovery of left
      ventricular function. It is important to emphasize that functional recovery does
      not denote total recovery of cardiac function; this is critical in terms of
      future pregnancies. This article presents the case of a young woman with
      peripartum cardiomyopathy and a review of the literature. (c)2001 by CHF, Inc.

PMID- 11828144
TI  - Epidemiology of congestive heart failure in three ethnic groups.
AB  - Congestive heart failure (CHF) is a leading cause of morbidity, disability, and
      mortality in old age, but little is known about the epidemiology of this
      condition in free-living minority populations. To determine the prevalence of CHF
      and associated risk factors in a multiethnic community, a population sample of
      2759 elderly (i.e., 65 years of age and older) African American (AA), Hispanic
      Cuban (HC), and white non-Hispanic (WNH) men and women from Miami-Dade County,
      Florida, were examined. There were 153 (5.6%) cases of self-reported CHF in the
      sample. The unadjusted prevalence rate of CHF was virtually identical among
      elderly AA (4.8%) and WNH (4.9%) but was significantly (p=0.04) lower than the
      rate among HC (6.8%). Sex- and ethnic-specific analyses showed that the highest
      prevalence rate of CHF was among HC women (8.2%). A multiple logistic analysis
      was used to calculate the odds ratio (OR) and 95% confidence interval (CI) of CHF
      in relation to age, sex, ethnicity, medical history, and smoking and alcohol
      drinking habits. Age (65-74 vs. 75-84; OR 1.7; CI 1.2-2.4; p=0.01), HC ethnic
      group (OR 1.5; CI 1.0-2.4; p=0.05), history of hypertension (OR 1.5; CI 1.1-2.1;
      p=0.02), history of myocardial infarction (OR 2.3; CI 1.5-3.5; p=0.0001), and
      history of diabetes mellitus (OR 1.9; CI 1.3-2.8; p=0.001) were directly,
      significantly, and independently associated with the prevalence of self-reported
      CHF. The findings here confirm those of prior studies in elderly white US
      residents, which indicate that heart attack, hypertension, and diabetes mellitus
      are major risk factors for CHF. The results also show that elderly AA and WNH
      have similar CHF prevalence rates. The higher CHF prevalence in elderly HC women
      found in this study requires further investigation. (c)2001 by CHF, Inc.

PMID- 11828145
TI  - Pharmacotherapy in congestive heart failure: Hyperkalemia in congestive heart
      failure.
AB  - Hyperkalemia is not an uncommon occurrence in the congestive heart failure
      patient, particularly when renal failure coexists. Hyperkalemia in CHF is
      typically medication-related. Its occurrence is inevitably linked to the
      simultaneous ingestion of angiotensin-converting enzyme inhibitors and beta
      blockers, and more recently, aldosterone receptor antagonists, such as
      spironolactone. The most devastating consequence of hyperkalemia is its
      cardiotoxicity that can be fairly insidious in its rate of development. The
      therapy of hyperkalemia in congestive heart failure can involve both acute and
      semiacute management phases. Acute hyperkalemia management includes measures that
      block the adverse membrane effects of hyperkalemia, such as intravenous calcium
      administration, and efforts to shift potassium intracellularly, such as occurs
      with intravenous bicarbonate and/or inhaled beta-agonists. Semiacute management
      of hyperkalemia includes measures to increase urinary potassium excretion and
      administration of binding resins, such as Kayexalate(r). Prevention is the
      cornerstone of hyperkalemia management in the heart failure patient and requires
      that careful attention be directed to both identifying exogenous sources of
      potassium and pinpointing the maximum tolerable dose of either an angiotensin
      converting enzyme inhibitor or an angiotensin-receptor blocker. (c)2001 by CHF,
      Inc.

PMID- 11828146
TI  - Difficult cases in heart failure: Raison d'Etre behind ACE inhibitors and AT1
      receptor combinations in chronic heart failure: chemical nuances or clinical
      significance?
AB  - The following case description serves to illustrate the difficulties often faced
      in clinical practice in implementing what appear to be fairly simple and clear
      evidence-based guidelines regarding angiotensin-converting enzyme (ACE)
      inhibitors and no clear guidelines regarding angiotensin receptor blocker (ARB)
      use or, more importantly, ACE inhibitor and ARB combinations in chronic heart
      failure. (c)2001 by CHF, Inc.

PMID- 11828148
TI  - Frontiers in congestive heart failure: Time course and extent of improvement of
      dysfunctioning myocardium in patients with coronary artery disease and severely
      depressed left ventricular function after revascularization--correlation with
      positron emission tomographic findings.

PMID- 11828147
TI  - Heart failure practice improvement effort in the outpatient setting: a health
      care financing administration initiative to improve the care of medicare
      beneficiaries with heart failure.
AB  - This column is the fourth in a series describing Health Care Financing
      Administration initiatives to improve care for Medicare beneficiaries with heart
      failure. The first three papers addressed the background, design, and baseline
      results of the Health Care Financing Administration national initiative to
      improve quality of inpatient care for heart failure through the activities of
      each state's Health Care Financing Administration contractor Peer Review
      Organization. This paper describes a smaller-scale but equally important
      endeavor: the Heart Failure Practice Improvement Effort, a pilot project to test
      the feasibility of assessing and improving heart failure care in the outpatient
      setting. (c)2001 by CHF, Inc.

PMID- 11828149
TI  - Frontiers in congestive heart failure: Hemodynamic and neurohormonal effects of
      continuous infusion of levosimendan in patients with congestive heart failure.

PMID- 11828150
TI  - Thinking of heart failure as a medical emergency.

PMID- 11828151
TI  - Evaluation and management of acutely decompensated chronic heart failure in the
      emergency department.
AB  - A wide range of patients with symptomatic heart failure seek treatment in the
      emergency department. While there is no single approach to the diversity of
      patients with acutely decompensated heart failure, certain overarching principles
      apply. For patients with acute pulmonary edema or cardiogenic shock, the first
      priority must be rapid stabilization and treatment of reversible problems. For
      patients with less dramatic presentations, a more systematic search for
      precipitating factors may be required. Therapy, in general, is directed at
      reversing dyspnea and/or hypoxemia caused by pulmonary edema, improving systemic
      perfusion, and reducing myocardial oxygen demand. While morphine and diuretics
      still have their traditional roles, vasodilators and inotropic agents play an
      increasingly important part in the modern pharmacologic approach to decompensated
      heart failure in the emergency department. After evaluation and stabilization in
      the emergency department, most patients will require hospital admission, although
      a subset of low-risk patients may be appropriate for discharge to home following
      a period of observation. Strategies to optimize emergency department care are
      likely to have an impact upon patient outcomes and upon resource utilization.
      (c)2001 by CHF, Inc.

PMID- 11828152
TI  - Cardiac resynchronization: a novel therapy for heart failure.
AB  - Despite advances in medical therapy for patients with congestive heart failure,
      morbidity and mortality remain high. Conduction abnormalities, such as left
      bundle branch block, right bundle branch block, and nonspecific conduction delay,
      are observed commonly in patients with dilated cardiomyopathy. In patients with
      heart failure, the presence of intraventricular conduction delay is associated
      with more severe mitral regurgitation and worsened left ventricular systolic and
      diastolic function, and is an independent risk factor for increased mortality.
      Conventional dual-chamber (right atrial and right ventricular) pacing with a
      short atrioventricular delay was initially introduced as therapy for patients
      with advanced congestive heart failure to improve diastolic dysfunction and
      reduce mitral regurgitation. The acute beneficial hemodynamic effects observed in
      early, uncontrolled studies were not confirmed in subsequent randomized,
      controlled studies with longer follow-up. Cardiac resynchronization with novel
      biventricular (left and right ventricular) pacing systems has resulted in
      hemodynamic and functional benefits in patients with congestive heart failure and
      an underlying intraventricular conduction delay. Improvements in cardiac index,
      systolic blood pressure, and functional class have been reported with
      biventricular pacing, both acutely and at more than 1 year of follow-up. These
      encouraging preliminary results with biventricular pacing in patients with
      congestive heart failure will be validated in two prospective, randomized,
      controlled trials, Multicenter InSync Randomized Clinical Evaluation (MIRACLE)
      and Comparison of Medical Therapy, Pacing, and Defibrillation in Chronic Heart
      Failure (COMPANION). These studies are designed to evaluate the long-term
      efficacy of biventricular pacing in improving exercise capacity and in reducing
      morbidity and mortality in patients with advanced, symptomatic congestive heart
      failure. (c)2001 by CHF, Inc.

PMID- 11828153
TI  - Dofetilide in patients with congestive heart failure and left ventricular
      dysfunction: safety aspects and effect on atrial fibrillation. The Danish
      Investigators of Arrhythmia and Mortality on Dofetilide (DIAMOND) Study Group. 
AB  - INTRODUCTION. Atrial fibrillation is a frequent cause of worsening of symptoms in
      patients with congestive heart failure. The drugs currently available for
      maintenance of sinus rhythm all have major side effects. METHODS. In 34 Danish
      coronary care units, 1518 patients with congestive heart failure and reduced left
      ventricular systolic function were randomized to receive either placebo or a new
      class III antiarrhythmic drug, dofetilide. The dose of dofetilide was adjusted
      according to the presence of atrial fibrillation, the length of the QT interval,
      and renal function. Patients were continuously monitored electrocardiographically
      for the first 3 days of the study. The primary end point was all-cause mortality
      and follow-up was for at least 1 year. RESULTS. In the dofetilide/placebo groups,
      311/317 patients died (41%/42%). The hazard ratio for dofetilide treatment was
      0.95 (95% confidence interval, 0.81-1.11). Treatment with dofetilide reduced
      worsening of heart failure significantly (hazard ratio, 0.75; 0.63-0.89). After 1
      year, 61% of patients with atrial fibrillation at the start of the study had
      converted to sinus rhythm on dofetilide, vs. 33% in the placebo group. After
      conversion to sinus rhythm, 78%/43% of patients in the dofetilide/placebo groups
      remained in sinus rhythm for at least 1 year. There were 25 instances (3%) of
      torsade de pointes ventricular tachycardia in the dofetilide group and none in
      the placebo group. CONCLUSION. In patients with congestive heart failure,
      dofetilide can effectively convert atrial fibrillation to sinus rhythm and
      maintain sinus rhythm after conversion. Hospitalization for congestive heart
      failure is reduced. Dofetilide does not affect mortality. (c)2001 by CHF, Inc.

PMID- 11828154
TI  - Using the transtheoretical approach to facilitate change in the heart failure
      population.
AB  - Heart failure is a significant health problem that requires a multidisciplinary
      approach for successful intervention. Five million Americans currently suffer
      from heart failure, resulting in an annual expenditure estimated at $20-$40
      billion. However, with early identification and intervention, the progression of
      heart failure can be stopped. Change in lifestyle and adherence to a prescribed
      plan of care recommended for heart failure treatment can lead to improved quality
      of life. The Transtheoretical Model provides a framework for facilitating the
      behavioral changes necessary for the optimal treatment of heart failure. Future
      research is suggested to evaluate outcomes of behavioral changes in heart failure
      populations upon implementation of this model. (c)2001 by CHF, Inc.

PMID- 11828155
TI  - Pharmacotherapy in congestive heart failure: Angiotensin-converting enzyme
      inhibitors and angiotensin receptor blockers in congestive heart failure: do they
      differ in their renal effects in man?
AB  - Angiotensin-converting enzyme (ACE) inhibitors are used in the management of a
      wide range of cardiovascular conditions, including congestive heart failure
      (CHF). Although the experimental evidence in support of their use in CHF is
      incontrovertible, their pattern of usage has failed to keep pace with the
      research findings. One factor that has fueled the hesitancy to use ACE inhibitors
      in CHF has been the concern that renal function might worsen upon their receipt.
      Although the glomerular filtration rate may decline when ACE inhibitor or
      angiotension receptor blocker therapy is started in CHF, in most cases it is not
      a reason to discontinue therapy other than temporarily. Although ACE inhibitors
      and angiotensin receptor blockers may differ theoretically in their renal
      effects, published information to date has not shown such a difference. (c)2001
      by CHF, Inc.

PMID- 11828156
TI  - Familial dilated cardiomyopathy--more than meets the eye.

PMID- 11828157
TI  - Difficult cases in heart failure: familial dilated cardiomyopathy.
AB  - While originally thought to be uncommon, familial dilated cardiomyopathy may
      occur quite often. Aside from symptoms of heart failure, these forms of dilated
      cardiomyopathy may be associated with arrhythmias and sudden death. The case
      detailed describes such a patient and emphasizes the importance of a careful
      family history. Also discussed is the importance of screening of first- and
      second-degree relatives of these patients. (c)2001 by CHF, Inc.

PMID- 11828159
TI  - Frontiers in congestive heart failure: Dilated cardiomyopathy in dialysis
      patients--beneficial effects of carvedilol: a double-blind, placebo-controlled
      trial.

PMID- 11828158
TI  - Profiles of quality improvements in heart failure care.
AB  - The Health Care Financing Administration, with its National Heart Failure
      project, has made heart failure care one of its targets for quality improvement.
      Previous columns have highlighted the clinical and epidemiologic background for
      the National Heart Failure project. This column provides "real-world" examples of
      hospitals improving care for their heart failure patients. (c)2001 by CHF, Inc.

PMID- 11828160
TI  - Frontiers in congestive heart failure: Prediction of hospital readmission for
      heart failure--development of a simple risk score based on administrative data.

PMID- 11828161
TI  - It takes a village.to improve heart failure care.

PMID- 11828162
TI  - Trastuzumab therapy and the heart: palliation at what cost?
AB  - Trastuzumab (Herceptin(r)), a monoclonal HER2 receptor blocker, was approved by
      the Food and Drug Administration in September, 1998 for the treatment of advanced
      breast carcinoma. It is rapidly emerging as an important drug for the treatment
      of metastatic breast cancer. The results of a pivotal trial revealed a 53%
      improvement in the response rate when trastuzumab was added to the standard
      chemotherapeutic regimen. However, a greater than four-fold increase in the
      occurrence of congestive heart failure was also noted. This novel agent has
      ushered in hope for thousands of women, but its use mandates that a clear
      understanding of its effects and relative risks be appreciated. Careful patient
      selection for the use of trastuzumab is critically important. It is prudent that
      cardiologists be aware of its cardiotoxicity, and that the risk/benefit ratio be
      clarified before its use in less invasive forms of breast cancer. (c)2001 CHF,
      Inc.

PMID- 11828163
TI  - Examination of left ventricular contractile reserve by Doppler myocardial imaging
      in patients with dilated cardiomyopathy.
AB  - Detection of left ventricular contractile reserve by means of dobutamine stress
      echocardiography is a well known technique. The aim of the present study was to
      detect velocity changes during the administration of dobutamine, to establish if
      Doppler myocardial imaging is a suitable method for determining left ventricular
      contractile reserve, and to determine if the technique provides more information
      than traditional stress echocardiography. Twenty-five patients (all males; mean
      age, 53.4 years) were examined for a clinical diagnosis of idiopathic dilated
      cardiomyopathy with a poor left ventricular systolic function (ejection fraction
      less than 30%). Doses of 5-10 and 20 mg/kg/min dobutamine were administered and
      elevated at 4-minute intervals. Ejection fraction was calculated using the
      Simpson rule. The peak systolic and the early and late diastolic velocities were
      measured in the basal segment of the septum and the inferior wall at baseline and
      at full dose of dobutamine. Results indicated that peak systolic velocity
      increased significantly, both in the septum (0.11+/-0.03 vs. 0.20+/-0.05 m/sec;
      p=0.001) and in the inferior wall (0.10+/-0.05 vs. 0.17+/-0.06 m/sec; p=0.03).
      Late diastolic velocities also increased significantly, both in the septum
      (0.17+/-0.05 vs. 0.22+/-0.07 m/sec; p=0.01) and in the inferior wall (0.18+/-0.08
      vs.0.21+/-0.02 m/sec; p=0.01). There was a significant linear correlation between
      the relative increases in basal ejection fraction value and in peak systolic
      velocity upon dobutamine stimulation. Patients were divided into responders and
      nonresponders based on responses in either ejection fraction (25% relative
      increase) or peak systolic velocity (5 cm/s increase). This study concludes that
      1) Doppler myocardial imaging is an adequate and simple technique to examine left
      ventricular contractile reserve; and 2) measurement of peak systolic velocity
      during dobutamine stimulation seems to be a simple and good indicator of left
      ventricular contractile reserve. (c)2001 CHF, Inc.

PMID- 11828164
TI  - Clinic dosing of beta blockers in chronic heart failure.
AB  - Beta blockers improve survival and reduce morbidity of patients with chronic
      heart failure. Stringent dosing guidelines calling for a 1-hour observation
      period after initiation or up-titration of beta-blocker therapy might limit the
      use of beta blockers and increase the expense involved. This study was conducted
      to determine the usefulness of this observation period. Data were collected from
      130 in-clinic postdosing observation periods for 34 stable chronic heart failure
      patients started on carvedilol. The mean left ventricular ejection fraction was
      0.22+/-0.09, and the mean functional class was 2.5+/-0.6. No patient had greater
      than first-degree heart block. Carvedilol was started at 3.125 or 6.25 mg b.i.d.,
      and the dose was doubled every 1-3 weeks. All patients were observed for 1-2
      hours after initiation or dosage increase, and blood pressure and heart rate were
      measured hourly. The maximal daily dose was 50+/-31 mg. In none of the
      observation periods was there a decrease in the dose of beta blockers
      administered in the clinic. The predosing mean blood pressure was 110+/-15/71+/
      10 mm Hg, and the mean heart rate was 78+/-13 bpm; the 1-hour postdosing mean
      blood pressure was 101+/-14/67+/-10 mm Hg (p is less than 0.001), and the heart
      rate was 78+/-13 bpm. The dose was decreased in six patients and medication was
      discontinued in three, all consequent to symptoms reported several days after
      dosage increase. Beta blockers can be safely initiated and up-titrated at home in
      properly selected and evaluated stable patients with chronic heart failure and
      severe left ventricular dysfunction resulting in mild or moderate impairment of
      functional capacity. (c)2001 by CHF, Inc.

PMID- 11828165
TI  - Chronotropic incompetence: a case report.
AB  - Chronotropic incompetence is generally defined as an inadequate heart rate
      response to exercise, but manifestations can vary. The incidence depends on
      underlying cardiac pathology and, to a lesser degree, on the cut-off value of the
      predicted heart rate during exercise. Different pathologies induce chronotropic
      incompetence. Its presence indicates an adverse outcome and is strongly
      correlated with coronary artery disease. Treatment consists of rate-responsive
      pacemakers; dual-sensor, adaptive pacemakers are superior to single-sensor, rate
      augmenting pacemakers. This case report illustrates the negative effect of
      chronotropic incompetence on daily activities and its amelioration by
      implantation of a rate-responsive pacemaker. (c)2001 by CHF, Inc.

PMID- 11828166
TI  - Difficult cases in heart failure: Left ventricular dysfunction related to septic
      shock masquerading as postpartum cardiomyopathy.
AB  - Peripartum cardiomyopathy, an uncommon cause of chronic heart failure, may
      present during the third trimester of pregnancy, but most often develops within 2
      months postpartum. The etiologies of heart failure during pregnancy and
      postpartum are numerous, however. The authors describe the case of a 25-year-old
      woman who developed severe, symptomatic heart failure following delivery and
      discuss their initial consideration of peripartum cardiomyopathy and the
      differential diagnostic features of this case. (c)2001 CHF, Inc.

PMID- 11828167
TI  - Improving heart failure care in the office setting.
AB  - This column is the sixth in a series describing Health Care Financing
      Administration (HCFA) initiatives to improve care for Medicare beneficiaries with
      heart failure. The fourth column addressed the Heart Failure Practice Improvement
      Effort, HCFA's pilot project to test the feasibility of assessing and improving
      heart failure care in the outpatient setting through the activities of HCFA
      contracted peer review organizations in eight states. This column is dedicated to
      illustrating the progress of the Heart Failure Practice Improvement Effort
      project at an individual state and practice level, focusing on the quality
      improvement activities in outpatient heart failure care conducted by the Colorado
      peer review organization. (c)2001 CHF, Inc.

PMID- 11828168
TI  - Frontiers in congestive heart failure: Skeletal muscle mass independently
      predicts peak oxygen consumption and ventilatory response during exercise in
      noncachetic patients with chronic heart failure.

PMID- 11828169
TI  - Frontiers in congestive heart failure: Aortic stenosis with severe left
      ventricular dysfunction and low transvalvular pressure gradients--risk
      stratification by low-dose dobutamine echocardiography.

PMID- 11828170
TI  - Propionic acidemia: a rare cause of cardiomyopathy.
AB  - The symptoms of propionic acidemia, an autosomal recessive disorder involving
      deficiency of the enzyme propionyl-coenzyme A carboxylase, are highly varied and
      may present at any time in the patient's life. Cardiomyopathy, a rare
      complication of this disorder, has been reported in only a small number of
      pediatric patients. The authors describe a case of adult-onset cardiomyopathy in
      a 23-year-old female with propionic acidemia diagnosed in early childhood and
      associated with multiple long-standing comorbidities. The possible mechanisms of
      propionic acidemia-associated cardiomyopathy, and the importance of early
      recognition and appropriate management, are discussed. (c)2001 CHF, Inc.

PMID- 11828171
TI  - High-output cardiac failure in a patient with prostate cancer.
AB  - The authors describe a case of high-output cardiac failure in a patient with
      rapidly progressing prostate cancer for which no previously described cause could
      be found. His new onset and increasingly worsening heart failure corresponded to
      the rapid spread of his prostate cancer. The authors hypothesize that a cytokine
      released from the neoplastic cells or the bone was responsible for the high
      output cardiac failure observed in this patient. (c)2001 CHF, Inc.

PMID- 11828173
TI  - Yet another milestone for CHF!

PMID- 11828172
TI  - When cancer and heart failure cross paths: a case report of severe cardiorenal
      compromise associated with the anti-CD20 monoclonal antibody rituximab in a
      patient with dilated cardiomyopathy.
AB  - The authors describe the case of a 41-year-old man with end-stage, nonischemic
      dilated cardiomyopathy of 11 years' duration. The patient had been deemed
      ineligible for transplantation, despite his young age, when he was diagnosed with
      non-Hodgkin's lymphoma 7 years previously. Since he had survived the lymphoma
      without significant chemotherapy, while his cardiovascular and renal status
      continued to deteriorate, the issue was revisited. In an attempt to at least
      render him eligible for an assist device, a novel, promising, and reportedly
      nontoxic immunomodulation therapy for his lymphoma was employed. This consisted
      of infusion of the monoclonal antibody rituximab, specifically targeting the CD20
      antigen on B cells. Despite testimonials concerning the benign nature of the
      treatment, the patient was unable to tolerate it and his clinical condition
      deteriorated rapidly, eventually leading to his death. The authors discuss
      potential mechanisms that might have accounted for the patient's cardiorenal
      compromise, with a focus on a very rare "cytokine release" syndrome attributed to
      this type of monoclonal antibody therapy and the probable interplay of cytokines
      in advanced heart failure. (c)2001 CHF, Inc.

PMID- 11828174
TI  - Nuggets, pearls, and vignettes of master heart failure clinicians. Part 2-the
      physical examination.

PMID- 11828175
TI  - Relation of functional capacity with the oxidative stress and antioxidants in
      chronic heart failure.
AB  - Chronic heart failure is a common, disabling disorder with high mortality.
      Oxidative stress may have both functional and structural effects on the
      myocardium, leading to myocardial decompensation. In this study, the authors
      examined the relationship of oxidative stress and functional capacity in patients
      with varying degrees of heart failure. Fifty-one patients with chronic heart
      failure and 31 control subjects were studied. The functional capacity of patients
      was determined. Plasma malondialdehyde, vitamin E, and beta-carotene levels were
      measured. The malondialdehyde levels were significantly different between control
      subjects and heart failure patients (p=0.03). There was a positive correlation
      between patients' malondialdehyde levels and New York Heart Association
      functional class (r=0.59; p<0.0001). There was a negative correlation between the
      functional class and vitamin E and beta-carotene levels (r=20.43; p<0.0001 and
      r=20.25; p<0.01, respectively). These data demonstrate that oxidative stress is
      increased systemically in patients with chronic heart failure. It seems that this
      increase correlates with functional class. (c)2001 CHF, Inc.

PMID- 11828176
TI  - Heart failure in beta-thalassemia.
AB  - Heart failure remains the main cause of death in beta-thalassemia despite the
      progress that has been made. Myocardial iron deposition alone does not affect
      left ventricular relaxation but directly causes left ventricular myocardial
      restriction with considerably elevated pulmonary pressure. This leads to symptoms
      and signs of predominantly right-sided heart failure, which is usually observed
      in elderly and severely hemosiderotic populations. Left ventricular systolic
      dysfunction and failure, which occurs in younger, less hemosiderotic populations,
      seems to be multifactorial in etiology. Apart from iron loading, immunogenetic
      risk factors trigger the mechanisms of left-sided heart failure development in
      the context of dilated-type cardiomyopathy. (c)2001 CHF, Inc.

PMID- 11828177
TI  - Optimal use of spironolactone for treatment of heart failure.
AB  - Spironolactone has recently been shown to have a favorable impact on the
      prognosis and functional status of patients with left ventricular systolic
      dysfunction and severe symptoms who are receiving standard therapy. However,
      participants in clinical studies of spironolactone represent a selected group.
      Clinicians managing a less selected group must be mindful of selection criteria
      and appropriate methods to monitor patients who are initiated on these
      medications. In this review, two case studies are described that demonstrate the
      importance of careful selection of candidates for spironolactone, the need for
      close laboratory and symptom monitoring, and the need for patients' active
      participation in reporting changes in their clinical status. (c)2001 CHF, Inc.

PMID- 11828178
TI  - Ambulatory blood pressure monitoring: technique and application in the study of
      cardiac dysfunction and congestive heart failure.
AB  - Ambulatory blood pressure monitoring has become a widely used method of blood
      pressure and heart rate evaluation in the free-living subject. Recently,
      ambulatory monitoring has become covered by Medicare for the evaluation of "white
      coat" hypertension. Although the technique provides only intermittent readings
      throughout the 24-hour period, average blood pressures obtained in this way
      correlate well with a variety of hypertensive disease processes and are also a
      better prognostic marker for future cardiovascular events than office blood
      pressure. Ambulatory blood pressure averages also correlate well with indices of
      diastolic dysfunction. In patients with congestive cardiac failure and systolic
      dysfunction, ambulatory monitoring suggests an impaired circadian blood pressure
      profile with high nocturnal blood pressure. Further research is needed on the
      relationship between ambulatory blood pressure and cardiac dysfunction, as well
      as the impact of observed circadian blood pressure changes on outcome. (c)2001
      CHF, Inc.

PMID- 11828179
TI  - Pharmacotherapy in congestive heart failure: angiotensin II and thirst:
      therapeutic considerations.
AB  - Angiotensin II is the effector peptide of the renin-angiotensin system and is
      involved in a wide range of physiologic functions that relate to volume control.
      In this regard, angiotensin II maintains and regulates salt and water balance, is
      critically involved in cardiovascular function, and governs thirst. When present
      in excess, angiotensin II can pathologically influence each of these functions.
      The role of angiotensin II in controlling sodium balance, in both renal
      insufficiency states and congestive heart failure, is clearly recognized.
      Alternatively, it is poorly appreciated that angiotensin II plays an important
      role in both normal and pathologic thirst states. The latter is a potential
      problem in both end-stage renal disease and congestive heart failure. Angiotensin
      converting enzyme (ACE) inhibitors and angiotensin receptor antagonists (AT1-RAs)
      have both been shown to reduce abnormal thirst drive. Whether an ACE inhibitor or
      an AT1-RA lessens thirst drive to any significant degree relates to its capacity
      to penetrate the blood-brain barrier. Head-to-head comparisons of ACE inhibitors
      and AT1-RAs, as to their effect on thirst drive, have not been undertaken in a
      systematic fashion; thus, until otherwise established, the effect of these
      compounds on thirst should be viewed as a class effect, albeit one that is likely
      to be dose-dependent. (c)2001 CHF, Inc.

PMID- 11828180
TI  - Frontiers in congestive heart failure: Utility of B-natriuretic peptide as a
      rapid, point-of-care test for screening patients undergoing echocardiography to
      determine left ventricular dysfunction.

PMID- 11828181
TI  - Frontiers in congestive heart failure: Utility of B-type natriuretic peptide in
      the diagnosis of congestive heart failure in an urgent care setting.

PMID- 11828182
TI  - Difficult cases in heart failure: reversible cardiomyopathy due to atrial
      fibrillation in a 46-year-old patient.
AB  - The authors describe the challenging case of a 46-year-old patient who presented
      with a 2-week history of exertional dyspnea, paroxysmal nocturnal dyspnea, and
      orthopnea. He was found to have left ventricular failure and atrial fibrillation
      with a rapid ventricular rate. Initial work-up revealed dilated cardiomyopathy
      with marked left ventricular dysfunction, without any obvious cause. He received
      standard medical therapy for left ventricular dysfunction and his symptoms
      improved. Electrical cardioversion to sinus rhythm and maintenance resulted in
      complete recovery of left ventricular function within 6 months. (c)2001 CHF, Inc.

PMID- 11828184
TI  - Preventive cardiology: more than just lipid lowering.

PMID- 11828183
TI  - Lessons learned from the national heart failure project: a center for medicare
      and medicaid services initiative to improve the care of medicare beneficiaries
      with heart failure.
AB  - This column is the seventh in a series reporting on the efforts of the Center for
      Medicare and Medicaid Services (CMS), formerly known as the Health Care Financing
      Administration, to improve care for Medicare beneficiaries with heart failure. In
      previous columns we have described the overall structure of Medicare quality
      improvement efforts, detailed the structure of the national inpatient fee-for
      service program known as the National Heart Failure project, and discussed the
      baseline quality indicator rates for the project, which are focused on rates of
      ejection fraction documentation and angiotensin-converting enzyme inhibitor
      prescription. In more recent columns, we reported on quality improvement projects
      from several participating hospitals, and on a pilot project exploring quality
      improvement efforts for heart failure based in physicians' offices. This column
      will focus on ways in which systematic examination of data, such as those from
      the National Heart Failure project, might shape future quality improvement and
      research efforts. The National Heart Failure project's quality indicator data are
      collected primarily to guide and evaluate the efforts of the CMS contractor peer
      review organizations to facilitate quality improvement efforts in hospitals
      throughout the United States. (c)2001 CHF, Inc.

PMID- 11828185
TI  - Analysis of lipoproteins and body mass index in professional football players.
AB  - Exercise is known to improve lipoprotein levels, whereas an elevated body mass
      index (BMI) is associated with less favorable lipoprotein levels. To date, there
      have been no reports of lipid analyses in elite athletes who also have BMIs in
      ranges considered unhealthful. The purpose of this study was to evaluate the
      lipid-lipoprotein profiles in a group of professional football players and to
      determine what association exists between these profiles and the players' BMIs.
      An observational study was conducted of 70 professional football players from one
      National Football League team. Measurements included BMI (kgcenter dotm(-2)), and
      fasting serum lipid analysis. BMI and position played were found to correlate
      (p<0.001), with linemen having the highest mean BMI, 38.1 kgcenter dotmsuperset
      or impliesminus sign2;. Comparing mean lipid values among BMI categories
      demonstrated lower high-density lipoprotein cholesterol levels (p<0.01), higher
      triglycerides (p<0.05), and higher total cholesterol/high-density lipoprotein
      cholesterol ratios (p<0.001) with an increasing BMI. Among the professional
      football players studied, a lower BMI was associated with a more favorable lipid
      lipoprotein profile. Among the elite athletes in this study with the highest
      BMIs, exercise may not confer the same protective benefits on cardiovascular risk
      as it does in those athletes with normal BMIs. (c)2001 CHF, Inc.

PMID- 11828186
TI  - Distribution of C-reactive protein and its relation to risk factors and coronary
      heart disease risk estimation in the National Health and Nutrition Examination
      Survey (NHANES) III.
AB  - The authors examined the distribution of, and risk factors associated with, the
      inflammatory marker C-reactive protein (CRP) among a large sample of non
      institutionalized American adults aged 30-74 years of age, and its relation to
      estimated 10-year coronary heart disease risk. The population studied comprised
      4472 men and 5212 women aged 30-74 years, without coronary heart disease, who had
      CRP measurements in the Third National Health and Nutrition Examination Survey
      (NHANES III). The 10-year risk of coronary heart disease was estimated from
      Framingham risk factor algorithms among those with CRP levels of less-than-or
      equal0.21 mg/dL, >0.21 to <0.5mg/dL, 0.5 to <1.0 mg/dL, and greater-than-or
      equal1.0 mg/dL. Mean (SD) levels of CRP were 0.41 (0.64) mg/dL in men and 0.55
      (0.91) mg/dL in women. Levels of at least 1 mg/dL were measured in 6.4% of men
      and 12.9% of women. CRP levels were highest among non-Hispanic black men and
      Mexican-American women. According to multiple logistic regression analysis,
      cigarette smoking and increased age, body mass index, and systolic blood pressure
      in men, and body mass index and diabetes in women, were strongly associated with
      a greater likelihood of CRP levels of greater-than-or-equal1.0 mg/dL (p<0.001).
      Among persons with CRP levels of less-than-or-equal0.21 mg/dL, >0.21 to <0.5
      mg/dL, 0.5 to <1.0 mg/dL and greater-than-or-equal1.0 mg/dL, the 10-year
      estimated risk of coronary heart disease were 13.4%, 17.6%, 19.6%, and 21.1%
      among men, respectively, and 2.7%, 3.6%, 4.1% and 4.3% among women, respectively
      (both p<0.001 across CRP categories); higher risks across CRP groups were also
      found among ethnic/gender subgroups. CRP remained a significant predictor of
      coronary heart disease risk in unadjusted and age-adjusted analyses. Conclusion.
      Elevation of CRP is associated with several major coronary heart disease risk
      factors and with unadjusted and age-adjusted projections of 10-year coronary
      heart disease risk in both men and women. (c)2001 CHF, Inc. Presented at the
      Fifth International Conference on Preventive Cardiology, Osaka, Japan, May, 2001.

PMID- 11828187
TI  - Emergence of obesity and cardiovascular risk for coronary artery disease: the
      Bogalusa Heart Study.
AB  - The underlying determinants of cardiovascular risk are governed by both genetic
      and lifestyle factors. One of the major adverse outcomes of unhealthy lifestyles
      is obesity, the genesis of which begins in childhood. Obesity, an important risk
      factor for atherosclerotic cardiovascular disease, type 2 diabetes, and
      hypertension, persists (tracks) strongly from adolescent years to adulthood.
      Secular trends toward increased obesity in the past 25 years have occurred in
      children and adults alike. Of interest, baseline adiposity precedes
      hyperinsulinemia in all age groups, independently of race, sex, and baseline
      insulin levels. Adiposity is an independent predictor of the risk of developing
      the cluster of risk variables of the metabolic syndrome X, beginning in
      childhood. Exposure to a multiple risk factor burden over time enhances the
      development of coronary atherosclerosis and hypertensive cardiovascular disease.
      In fact, autopsy studies in youths have shown that the extent of fibrotic
      atherosclerotic plaques in coronary arteries, measured antemortem, increases
      markedly with the presence of syndrome X risk variables. Further, in overweight
      children, insulin levels are associated with left ventricular mass. In young
      people, overnutrition, coupled with physical inactivity, leads to weight gain.
      Since obesity, unhealthy dietary habits, and a sedentary lifestyle are
      interrelated and modifiable, prevention and intervention must begin in early
      life. (c)2001 CHF, Inc.

PMID- 11828188
TI  - Response of Blood Lipids to Physical Exercise in Elderly Subjects.
AB  - Regular physical activity plays an important role in nonpharmacologic management
      of hyperlipidemia, in both the primary and secondary prevention of coronary heart
      disease. Training intensity and duration, health status (especially the presence
      of cardiovascular disease), and concomitant changes in body mass and dietary
      habits are the most important factors that can modify the physical activity-blood
      lipid profile relationship in the elderly. The benefit of regular exercise goes
      beyond direct influence on blood lipids; it aids in reducing weight, decreasing
      fat mass, increasing lean body mass, reducing elevated blood pressure, and
      increasing insulin sensitivity. Regular physical activity has become widely
      recommended as an important element of healthy and successful aging and should be
      encouraged in individuals without contraindications. (c)2001 CHF, Inc.

PMID- 11828190
TI  - Perspectives: NCEP III-A Call to Arms!

PMID- 11828189
TI  - Effect of Controlling Hypercholesterolemia on Myocardial Ischemia.
AB  - Hypercholesterolemia causes myocardial ischemia, even in the absence of
      obstructive coronary artery lesions. Reductions in cholesterol are associated
      with improved clinical outcomes that may reflect reversal of endothelial
      dysfunction, lesion regression, or both. This review explores experimental and
      clinical evidence that supports these observations. These include: 1) mechanisms
      by which hypercholesterolemia (and other risk factors for coronary artery
      disease) causes endothelial dysfunction; 2) the role that hypercholesterolemia
      and endothelial dysfunction play in atherogenesis, lesion complications, and
      clinical ischemic syndromes; and 3) compelling data that illustrate the benefits
      of cholesterol control. The latter include transformation of the plaque lipid
      composition to a more favorable profile, improved blood pressure control,
      normalization of exercise test results, improved exercise tolerance, and reversal
      or prevention of myocardial perfusion abnormalities. Collectively, these data
      support the notion that control of cholesterol is important to both the
      prevention and treatment of cardiac disease.) (c)2001 CHF, Inc.

PMID- 11828191
TI  - Did You Know? Updated Guidelines for Antithrombotic Therapy in Atrial
      Fibrillation.

PMID- 11828192
TI  - Reflections on cardiovascular risk stratification and prevention.

PMID- 11828193
TI  - Cardiovascular disease risk stratification and comparison in a California
      population.
AB  - This study was designed to identify the need for primary prevention of
      cardiovascular disease in an HMO population and to develop appropriate
      interventions for individuals in different risk groups, based on risk
      stratification and comparison. The analysis is based on a cross-sectional survey
      of the HMO members of a large employer group. Respondents (n=17,878) were
      stratified based on the Framingham model; 34% of respondents without
      cardiovascular disease were classified as moderate to high attributable risk for
      the disease, and 66% were classified as low attributable risk. Results of
      logistic regression analyses suggest that, compared with respondents with pre
      existing cardiovascular disease, moderate- to high-risk respondents are more
      likely to smoke, have unhealthy diets, and be overweight, hypertensive, and
      hypercholesterolemic. More low-risk respondents had unhealthy diets than did
      those with pre-existing cardiovascular disease. There were no differences between
      these groups for physical activity and stress. Respondents had fewer modifiable
      risk factors and healthier lifestyles than did those who were at risk. These
      findings suggest that primary prevention should be enhanced, especially among
      those with significantly increased risk for the disease. Moreover, the approaches
      of this project-population-based risk assessment, stratification, and comparison
      were instrumental in identifying the target population and designing appropriate
      interventions. (c) 2001 by CHF, Inc.

PMID- 11828194
TI  - Six-month patient outcomes in a preventive cardiology center.
AB  - More effective ways to improve lifestyle behaviors need to be developed. Two
      hundred forty adult patients at a preventive cardiology clinic were randomly
      assigned to receive either one or five sessions of behavioral instruction to
      improve cardiovascular risk behaviors. Results for 102 patients from 6-month
      follow-up data revealed few significant differences between the two groups.
      However, in the two groups combined, there were significant reductions in total
      calories, percent of calories from total fat, percent of calories from saturated
      and monounsaturated fat, and dietary cholesterol. Reductions were also found in
      systolic blood pressure, triglycerides, body mass index, and weight. In multiple
      regression analyses, changes in physiologic variables were primarily associated
      with baseline and demographic characteristics. Changes in total calories, percent
      of calories from polyunsaturated fat, and walking were predicted by changes in
      social support or knowledge. Although most patients improved, the intensity of
      behavior change instruction was not related to the amount of change in
      cardiovascular risk factors. (c) 2001 by CHF, Inc.

PMID- 11828195
TI  - Health perception of patients after cardiovascular risk detection and after
      intervention in general practice.
AB  - BACKGROUND. To explore unfavorable effects, health perception was assessed in
      patients enrolled in a cardiovascular program in general practice. METHODS. A
      prospective questionnaire survey was conducted shortly after risk detection and
      after 1 year of intervention. Patients (n=413) with an elevated risk were
      selected from 27 practices in The Netherlands. The outcome measure was patients'
      perceptions of their general health status. RESULTS. The response rate was 62%.
      Two thirds of the patients did not show any change in general health status at
      either point in time. Substantially more patients showed improvement after 1 year
      of intervention. Compared to reference data, no major differences were found.
      CONCLUSION. Enrollment in a cardiovascular risk detection and intervention
      program did not lead to unfavorable perceptions of general health status, either
      shortly after risk detection or after 1 year of intervention. (c) 2001 by CHF,
      Inc.

PMID- 11828196
TI  - Maintaining the endothelium: preventive strategies for vessel integrity.
AB  - The endothelium is a diaphanous membrane, only one cell layer thick, that lines
      all of our blood vessels. Despite its apparent fragility, it exerts profound
      control over vascular tone, structure, and intersection with circulating blood
      elements. One of the factors that the endothelium synthesizes is nitric oxide,
      which is the most potent endogenous vasodilator known. In addition to its blood
      flow regulating effects, nitric oxide also inhibits key processes in
      atherosclerosis, including monocyte adherence, platelet aggregation, and
      proliferation of vascular smooth muscle cells. Nitric oxide synthesis is
      impaired, and its degradation is accelerated, in many of the conditions
      associated with atherosclerosis, including hypercholesterolemia. Restoration of
      nitric oxide synthesis and activity in these disorders can improve blood flow,
      relieve symptoms, and perhaps reduce the progression of atherosclerosis.(c) 2001
      by CHF, Inc.

PMID- 11828197
TI  - Perspectives: Benefits of a new, nonsystemic lipid-lowering agent: the
      clinician's perspective.

PMID- 11828198
TI  - Original metric vs. standardized effect sizes for meta-analysis of clinical data.
AB  - This study compared the use of the original metric effect size with the
      standardized effect size for clinical data in meta-analysis. The example data set
      included 17 controlled clinical trials dealing with the effects of progressive
      resistance exercise on resting diastolic blood pressure in adults. Original
      metric effect size showed a decrease in resting diastolic blood pressure of -2.07
      mm Hg (95% confidence interval, -3.60 to -0.54). From a clinical standpoint, this
      is considered a "small" effect. The standardized approach showed an average
      effect of -0.21, 95% CI= -0.39 to -0.02. This is also considered a "smal" effect.
      When possible, use of the original metric is preferred because it can be more
      clinically meaningful and will enhance interpretation of blood pressure results
      for a wider range of readers. (c) 2001 by CHF, Inc

PMID- 11828199
TI  - Did You Know? A predictable "MIRACL"

PMID- 11828200
TI  - Wine and coronary heart disease: paradise lost?

PMID- 11828201
TI  - Hypertension and the risk of acute myocardial infarction in Argentina. The
      Argentine Factores de Riesgo Coronario en America del Sur (FRICAS) Investigators.
AB  - The relationship between a history of hypertension and the quality of its control
      in routine clinical practice and the risk of acute myocardial infarction was
      examined in a multicenter, case-control study conducted in Argentina between
      November 1991 and August 1994, within the framework of the FRICAS study. The
      cases were 939 patients with acute myocardial infarction and without a history of
      ischemic heart disease. The controls were 949 subjects identified in the same
      centers as the cases and admitted with a wide spectrum of acute disorders
      unrelated to known or suspected risk factors for acute myocardial infarction. The
      odds ratios and the 95% confidence intervals were derived from multiple logistic
      regression equations, including terms for age, gender, education, social status,
      exercise, smoking status, cholesterolemia, history of diabetes, body mass index,
      and family history of myocardial infarction. The quality of hypertension control
      was assessed with the most recent blood pressure reading reported by the
      subjects. Seventy-two percent of hypertensive cases and 62.6% of hypertensive
      controls had a history of antihypertensive therapy by self-report, when admitted
      to the medical center. The adjusted odds ratio for acute myocardial infarction
      due to hypertension was 2.58 (95% confidence interval, 2.08-3.19). The odds ratio
      was 2.42 (95% confidence interval, 1.88-3.11) when hypertensives reported that
      their greatest systolic value was below 200 mm Hg (moderate status) and 4.12 (95%
      confidence interval, 2.87-5.89) when it was above 200 mm Hg (severe status). When
      the highest diastolic blood pressure value was below 120 mm Hg (moderate status),
      the risk increased to 2.48 (95% confidence intervals, 1.90-3.24) and to 4.12 (95%
      confidence interval, 2.83-5.99) when it was above 120 mm Hg (severe status). If
      the most recent systolic blood pressure was less-than-or-equal140 mm Hg, the odds
      ratio was 2.59 (95% confidence interval, 1.96-3.41), and it was 3.42 (95%
      confidence interval, 2.40-4.87) when the value was >140 mm Hg. If the most recent
      diastolic blood pressure was less-than-or-equal90 mm Hg, the risk increased more
      than two fold (odds ratio=2.48; 95% confidence interval, 1.91-3.22), and if it
      was >90 mm Hg, it increased nearly four-fold (odds ratio=3.72; 95% confidence
      interval, 2.33-5.96). In smokers, the odds ratio was 2.28 in the absence of
      hypertension and increased to 7.51 when hypertension was present. In this
      Argentine population, hypertension is a strong and independent risk factor for
      acute myocardial infarction. In routine clinical practice, the control of blood
      pressure to levels below 140/90 seems to be required in order to reduce part (but
      not all) of the risk of acute myocardial infarction in hypertensive patients. (c)
      2001 by CHF, Inc.

PMID- 11828202
TI  - The evolving role of high-density lipoprotein in reducing cardiovascular risk.
AB  - In many patients with coronary artery disease, a low level of high-density
      lipoprotein cholesterol (HDL-C), rather than substantially elevated low-density
      lipoprotein cholesterol (LDL-C), is often the predominant lipid abnormality.
      Although the National Cholesterol Education Program treatment guidelines include
      HDL-C concentration as a major risk factor for primary prevention, the
      guidelines' emphasis on LDL-C as the primary target of therapy may cause
      uncertainty as to whether risk reduction strategies should focus on lowering LDL
      C or raising HDL-C in high-risk patients with low HDL-C. Recent clinical trial
      evidence and epidemiologic data suggest that HDL-C should play a more important
      role in risk assessment, and that the definition of low HDL-C may need adjustment
      from the current National Cholesterol Education Program definition of <35 mg/dL
      to perhaps <40 mg/dL in men and <45 mg/dL in women. Patients with low HDL-C
      should receive aggressive risk factor modification, and more emphasis on
      increasing HDL-C may be warranted in addition to lowering LDL-C. (c) 2001 by CHF,
      Inc.

PMID- 11828204
TI  - Determination of risk for atrial fibrillation utilizing precise P wave duration
      measuring methodology.
AB  - Increased duration of the P wave has been shown to be an indicator of increased
      risk for atrial fibrillation. This paper describes a method of obtaining the
      "true P wave duration" from previously recorded six-channel electrocardiograms,
      using readily available personal computers and software instead of more expensive
      P wave signal averaging devices. P wave duration in the atrial fibrillation group
      was significantly greater than in the nonfibrillation group. Measuring true P
      wave duration has greater sensitivity and specificity than measuring
      "conventional P wave duration." Precise measurement of P wave duration may prove
      to be an important factor in determining the risk of atrial arrhythmias. (c) 2001
      by CHF, Inc.

PMID- 11828203
TI  - Aerobic exercise and resting blood pressure: a meta-analytic review of
      randomized, controlled trials.
AB  - In this study the authors used the meta-analytic approach to examine the effects
      of aerobic exercise on resting systolic and diastolic blood pressure in adults.
      Forty-seven clinical trials representing a total of 72 effect sizes in 2543
      subjects (1653 exercise, 890 control) met the criteria for inclusion.
      Statistically significant exercise-minus-control decreases were found for changes
      in resting systolic and diastolic blood pressure in both hypertensive (systolic, 
      6 mm Hg, 95% CI, -8 to -3; diastolic, -5 mm Hg, 95% CI, -7 to -3) and
      normotensive (systolic, -2 mm Hg, 95% CI, -3 to -1; diastolic, -1 mm Hg, 95% CI, 
      2 to -1) groups. The differences between groups were statistically significant
      (systolic, p=0.008; diastolic, p=0.000). Relative decreases were approximately 4%
      (systolic) and 5% (diastolic) in hypertensives, and 2% (systolic) and 1%
      (diastolic) in normotensives. It was concluded that aerobic exercise reduces
      resting systolic and diastolic blood pressure in adults. (c) 2001 by CHF, Inc.

PMID- 11828205
TI  - Estrogen levels and lipid peroxidation following exercise.
AB  - Recent large-scale clinical trials have confirmed that estrogens are powerful
      antioxidants that effectively prevent lipid peroxidation. In particular, estrogen
      decreases oxidative modification of low-density lipoprotein both in vitro and in
      vivo. Estrogen levels fluctuate during the menstrual cycle and during
      perimenopause, and they are permanently depressed at menopause. Thus, it is of
      interest to evaluate the lipid peroxidation response under conditions of low
      estrogen status. It is of additional interest to evaluate lipid peroxidation
      under such conditions in response to situations that augment free radical
      production, such as exercise. Aerobic exercise, and more recently anaerobic
      exercise regimens, are reported to variably affect free radical production and
      lipid peroxidation. In addition to the exercising woman's estrogen status and
      menstrual history, other factors to consider when evaluating an exercising
      woman's risk for increased lipid peroxidation include the intensity of exercise
      and/or the woman's fitness level as well as her current dietary antioxidant
      status. (c) 2001 by CHF, Inc.

PMID- 11828206
TI  - Perspectives-- Focus on statins: lipid-lowering mechanisms and beyond.
AB  - Recent large-scale clinical trials have confirmed that statin-induced lipid
      modification can significantly reduce cardiovascular morbidity and mortality.
      Statins are now the drugs of choice in lipid management but fail to meet the
      criteria for an ideal therapy in several respects. Therefore, the search
      continues for lipid modifying treatments that meet even higher standards. Lipid
      lowering drugs currently in development may meet these more exacting standards
      and together with complementary methods could ultimately form ideal combination
      therapy. (c) 2001 by CHF, Inc.

PMID- 11828207
TI  - Congenital cardiovascular disease in the adult patient: imaging update.

PMID- 11828208
TI  - Indirect CT venography following CT pulmonary angiography: spectrum of CT
      findings.
AB  - SUMMARY: Pulmonary embolism (PE) and deep venous thrombosis (DVT) represent two
      manifestations of the same syndrome, venous thromboembolism. Contrast-enhanced
      computed tomography (CT) angiography is a practical, efficient alternative to
      conventional imaging for PE. Following the pulmonary examination, the inferior
      vena cava (IVC) and the iliac, femoral, and popliteal veins can be studied with
      CT without additional intravenous contrast administration. Indirect CT venography
      (CTV) after CT pulmonary angiography (CTPA) simplifies and shortens venous
      thromboembolism work-up. Initial studies indicate that CTV is comparable to
      ultrasound in the evaluation of femoral/popliteal DVT. CTV has the advantage of
      evaluating the iliac veins and inferior vena cava, vessels poorly seen on
      sonography and venography. Combining CTV with CTPA increases confidence in
      withholding treatment when results for both the pulmonary arteries and leg veins
      are negative and increases the diagnosis of venous thromboembolism by 25% over
      CTPA alone. This pictorial essay will review the normal venous anatomy, CTV
      technique, and the findings of acute and chronic DVT. Interpretive pitfalls and
      alternative diagnoses are also reviewed.

PMID- 11828209
TI  - The imaging spectrum of pulmonary tuberculosis in AIDS.
AB  - SUMMARY: Pulmonary tuberculosis (TB) is the major opportunistic infection of
      acquired immunodeficiency syndrome (AIDS) on a worldwide basis. The purpose of
      this pictorial essay is to illustrate and review the spectrum of imaging findings
      associated with pulmonary TB in patients with AIDS and to describe important
      factors that may complicate the radiographic follow-up of patients being treated
      for TB.

PMID- 11828210
TI  - Systemic arterial supply to the normal basal segments of the left lower lobe:
      radiographic and CT findings in 11 patients.
AB  - SUMMARY: To assess the radiologic findings of systemic arterial supply to the
      normal basal segments of the left lower lobe, chest radiographs and CT scans of
      all 11 patients were reviewed retrospectively by two chest radiologists. On
      posteroanterior chest radiographs (n = 11), the anomalous systemic artery arising
      from the descending thoracic aorta was shown as a retrocardiac mass (n = 11).
      Absence of normal lower lobar pulmonary artery shadow (n = 11), partial
      obliteration of the descending aortic interface (n = 9), and increased
      interstitial markings in left lower lung zone (n = 8) were also noted. On
      contrast-enhanced scans (n = 11), abrupt tapering of the normal left lower lobar
      pulmonary artery distal to the origin of superior segmental artery (n = 11),
      aberrant systemic artery originating from the descending aorta (n = 11), mild
      volume loss in the left lower lobe (n = 11), diffuse dilatation of the
      intrapulmonary peripheral vasculature (n = 11) and areas of ground-glass opacity
      (n = 10) in the basal segments of the left lower lobe were seen. Because chest
      radiography and CT consistently demonstrate several combinations of
      characteristic findings, conventional aortography may not be necessary for proper
      diagnosis of this anomaly.

PMID- 11828211
TI  - Small pulmonary nodules on CT accompanying surgically resectable lung cancer:
      likelihood of malignancy.
AB  - SUMMARY: The aim of this study was to determine the likelihood of malignancy in
      small nodules in the nonprimary lobe in patients with resectable bronchogenic
      carcinoma. In 141 patients who underwent curative resection of bronchogenic
      carcinoma and had adequate follow-up CT examinations, the presence of small
      nodules in the nonprimary lobe preoperatively and change of preexisting nodules,
      if any, was assessed. The criteria used to determine benignity of a nodule was
      stability or decrease in size for 24 months on CT. Histopathology of the nodules
      was reviewed for an additional 10 patients who underwent surgical biopsy for an
      accompanying nodule before curative surgery. Sixty-two (44%) of 141 patients had
      a total of 138 small (< or = 10 mm) nodules in the nonprimary lobes (< 5 mm in
      113, 5-10 mm in 25). Of these 138 nodules, 132 were benign with only six nodules
      malignant (with histopathologic confirmation for the enlarging nodules). The 132
      benign nodules showed no change (n = 120), decrease in size (n = 11), or increase
      in size (n = 1) on follow-up studies, with the single enlarging nodule proved
      benign on biopsy. In 10 patients who had a preoperative biopsy of a single
      preexisting nodule in the nonprimary lobe (< 5 mm = 1; 5-10 mm = 5; > 10 mm = 4)
      two proved to be malignant (both > 10 mm) and eight were benign. Most small (< 10
      mm) nodules associated with resectable bronchogenic carcinoma are benign,
      consistent with published results of other studies. However, a small number of
      nodules are malignant and CT does not reliably distinguish between benign and
      malignant nodules.

PMID- 11828212
TI  - Inspiratory and expiratory helical CT of normal adults: comparison of thin
      section scans and minimum intensity projection images.
AB  - SUMMARY: To evaluate and compare thin section CT scans (TSS) and minimum
      intensity projection images (MinIPs) in healthy individuals, 10 nonsmokers with
      normal pulmonary function tests were studied using ten 1-mm collimated, helically
      acquired TSS images after full inspiration and expiration at two anatomic levels.
      Ten-millimeter-thick MinIPs were generated from the helical scans. Two thoracic
      radiologists compared TSS and MinIPs for artifacts and air trapping. Hounsfield
      unit (HU) measurements of TSS and MinIPs were obtained. The lung parenchyma on
      MinIPs demonstrates a smooth anterior-to-posterior attenuation gradient,
      accentuated by expiration. Motion and beam-hardening artifacts on TSS images
      resulted in regions of high and low attenuation on MinIPs, respectively.
      Expiratory TSS and MinIPs demonstrated air trapping (n = 31/40; range, 0-25%;
      mean, 7.2%). In comparison with TSS, MinIPs improved the conspicuity of air
      trapping (n = 20) and appeared to detect more air trapping (n = 7). No
      statistical differences were found when comparing the mean HU values of TSS and
      MinIPs. MinIPs demonstrated a smooth anterior-to-posterior attenuation gradient.
      Compared with TSS, MinIPs improve the conspicuity of air trapping in healthy
      individuals. Therefore, expiratory MinIPs may be useful in detecting air trapping
      as a result of disease.

PMID- 11828213
TI  - Spectrum of CT findings in nosocomial Pseudomonas aeruginosa pneumonia.
AB  - The purpose of this study was to evaluate CT findings in nosocomial Pseudomonas
      aeruginosa Pneumonia (PAP) and to compare features of PAP in patients with
      isolated P. aeruginosa cultures and those with coexistent infections. A
      retrospective database search revealed 28 patients with nosocomial PAP (12 men,
      16 women; mean age, 57 years) in which thoracic CT had been performed within a
      mean of 1.7 days from the time of respiratory culture. Two chest radiologists
      blinded to culture data performed a consensus reading noting distribution and
      pattern of consolidation, ground-glass opacity, nodules, peribronchial
      infiltration, necrosis, effusions, and pleural enhancement. Coexistent
      respiratory cultures were recorded. Consolidation was present in all patients,
      involving multiple lobes in 23 (82%) and demonstrating upper zonal involvement in
      23 (82%). Nodular features were present in 14 (50%), including tree-in-bud
      patterns with centrilobular distributions in 9 (64%) and larger, randomly
      distributed nodules in 5 (36%). Five of five patients with consolidations limited
      to the lower lung zones had associated upper lung nodules. Ground-glass opacity
      was seen in nine (31%) and peribronchial infiltration in 16 (57%). Necrosis was
      present in eight (29%). Thirteen (46%) bilateral and five (18%) unilateral
      pleural effusions were present with enhancement occurring in two (1%). Coexistent
      positive respiratory cultures were identified in 13 patients. The distribution of
      consolidation, frequency and distribution of nodules, and frequency of necrosis
      did not differ significantly between patients with and without other positive
      cultures. With CT, PAP most commonly presents with multifocal airspace
      consolidation. Nodular features were identified in half, with one-third
      demonstrating tree-in-bud opacities. Unsuspected necrosis occurred in one-third
      of cases. CT findings in patients with and without other respiratory isolates did
      not differ in the distribution and frequency of consolidations, nodularity, or
      necrosis.

PMID- 11828214
TI  - The chest in profile.
AB  - SUMMARY: Radiology has been abounding with technological advances since the chest
      film first became the mainstay in diagnosing thoracic disease, and yet the
      conventional chest examination has endured as a front-line tool. The ability to
      perceive structural alterations is facilitated by a solid foundation in anatomy,
      which should be easy to achieve in a practice environment in which CT has become
      so commonplace. Not only is knowledge of anatomic nuances important for analysis
      of conventional radiographs, but it can only be an asset as multiplanar imaging
      is increasingly utilized and new modalities are developed over time. Some
      fundamental anatomic variations are revisited here through correlating the
      perspective provided by the lateral radiograph with the equally common one
      provided by routine axial CT images.

PMID- 11828215
TI  - Pulmonary aspergillosis in an immunocompetent patient.
AB  - SUMMARY: A case of an immunocompetent patient with severe Aspergillus infection
      and radiographic findings typically described with angioinvasive aspergillosis is
      presented. When Aspergillus is isolated from the sputum in a patient with normal
      immunity, invasive aspergillosis should be considered when there are extensive
      radiographic findings characteristic of invasive fungal disease.

PMID- 11828216
TI  - Discrete pleural nodules associated with a parasternal mass: an unusual
      manifestation of tuberculosis.
AB  - SUMMARY: The case presented describes an unusual appearance of thoracic
      tuberculosis with multiple pleural nodules associated with a parasternal mass as
      depicted on computed tomography. The patient is a 22-year-old woman who presented
      with pleuritic chest pain, a left parasternal mass, and weight loss. The pleura
      of the left hemithorax was studded with multiple low-attenuation, rim-enhancing
      nodules, and a left parasternal mass with similar imaging features was seen
      anterior to an enlarged left internal mammary lymph node. There were no pulmonary
      parenchymal changes nor any mediastinal or hilar lymphadenopathy. Cytologic
      examination of the specimen obtained with fine needle aspiration of the pleural
      and parasternal masses yielded granulomatous inflammation. The symptoms remitted
      with antituberculous chemotherapy and a follow-up CT obtained 6 months later
      showed complete resolution of the pleural nodules and parasternal mass and
      considerable regression of the left internal mammary lymph node. Involvement of
      the pleura with discrete nodules in the absence of parenchymal changes or
      mediastinal lymphadenopathy is rare in tuberculosis. To the best of the present
      authors' knowledge, the combination of a tuberculous parasternal mass and
      multiple pleural nodules as the sole manifestations of thoracic tuberculosis has
      not been reported previously.

PMID- 11828217
TI  - Tension pneumothorax associated with hydatid cyst rupture.
AB  - SUMMARY: Hydatid disease is common in Turkey. Tension pneumothorax is rare, but
      it is an important complication of the hydatid cyst with significant morbidity
      and mortality. Tension hydropneumothorax secondary to the rupture of a hydatid
      cyst was detected in 5 of 185 spontaneous pneumothorax cases that were treated in
      the authors' clinic between 1992 and 1998. All patients were subjected to
      surgical treatment after urgent tube thoracostomy. No mortality or recurrence was
      observed at follow-ups of 9 to 24 months.

PMID- 11828218
TI  - Hypersensitivity pneumonitis producing a BOOP-like reaction: HRCT/pathologic
      correlation.
AB  - SUMMARY: The authors report an unusual case of hypersensitivity pneumonitis
      presenting on high-resolution CT as large and sharply defined nodular opacities
      caused by extensive bronchiolitis obliterans with organizing pneumonia. Many of
      the nodules were surrounded by a halo of ground-glass attenuation. To the
      authors' knowledge, this is the first time these features have been described in
      association with hypersensitivity pneumonitis.

PMID- 11828219
TI  - Intracavitary hematoma simulating mycetoma formation.
AB  - SUMMARY: This case report details the initial radiographic findings of a patient
      with mixed connective-tissue disease who presented with significant hemoptysis.
      Several radiographic findings suggested mycetoma formation, prompting appropriate
      antibiotic therapy; however, the rapid resolution and subsequent reappearance of
      the lesion on serial images pointed toward a diagnosis of hemorrhage into a
      preexisting cavity. Chest radiographic and computed tomographic findings commonly
      described as pathognomonic for the diagnosis of mycetoma are, in fact,
      nonspecific and can be simulated by several other entities that result in
      intracavitary masses. Familiarity with these radiographic "mimickers" of mycetoma
      will aid in avoiding misdiagnosis and unnecessary or improper invasive
      interventions when the appropriate clinical history and course of disease are
      appreciated.

PMID- 11828220
TI  - Endobronchial growth patterns in peripheral adenocarcinoma of the lung.
AB  - SUMMARY: A 59-year-old man who underwent chest radiography to exclude pneumonia
      showed an irregular nodular shadow in the left lower lung. A subsequent CT scan
      revealed an irregularly shaped soft-tissue mass consisting of two components: a
      peripheral round mass with spiculated margins and a well-circumscribed branching
      tubular opacity extending medially. Pathologically, the nodular lesion was found
      to be a poorly differentiated adenocarcinoma, and was contiguous with the central
      tubular opacity that represented the endobronchial polypoid growth of tumor from
      the periphery towards the hilum. The bronchial wall was found to be uninvolved by
      tumor. The centripetal pattern of endobronchial growth of a peripheral
      adenocarcinoma has not, to the authors' knowledge been described previously.

PMID- 11828221
TI  - Imaging findings of an intercostal hemangioma.
AB  - SUMMARY: The authors present the imaging findings in a 44-year-old woman with a
      rare intercostal hemangioma that originated from the connective tissue between
      the intercostal muscle and parietal pleura and protruded into the thoracic
      cavity. The contrast-enhanced computed tomography (CT) showed a markedly
      enhancing mass, whereas dynamic magnetic resonance (MR) images showed
      heterogeneous and strong enhancement with incomplete early eccentric enhancement
      peripherally followed by complete filling-in on delayed scans. The imaging
      features of CT and MR imaging of a hemangioma may be useful for proper
      preoperative diagnosis.

PMID- 11828222
TI  - Imaging characteristics of anomalous left coronary artery from the pulmonary
      artery.
AB  - SUMMARY: The authors report the imaging characteristics of the anomalous origin
      of the left coronary artery from the pulmonary artery in a 6 1/2-month-old male
      infant using electrocardiography, echocardiography, angiography, and electron
      beam computed tomography. The patient presented with tachycardia, prolonged and
      interrupted feeding, failure to thrive, and myocardial infarction, and after
      diagnosis of the anomalous origin of the left coronary artery, survived the
      reimplantation of the left coronary artery directly to the ascending aorta. When
      reviewed 7 months after surgery, echocardiography showed improved left
      ventricular function and surface electrocardiography showed regression of
      pathologic Q waves in leads I, V 4, V 5, and V 6.

PMID- 11828223
TI  - Hyponatremia in runners requiring on-site medical treatment at a single marathon.
AB  - STUDY OBJECTIVE: Literature reports indicate an increasing number of cases of
      hyponatremia in athletes participating in moderate endurance events such as
      standard marathons. In this study, we evaluated the incidence of hyponatremia in
      marathon finishers requiring medical treatment on-site and attempted to assess
      the contribution of fluid type ingested and nonsteroidal antiinflammatory drug
      (NSAID) use to the development of hyponatremia. METHODS: We examined a
      prospective, convenience sample of runners requiring intravenous hydration at the
      final medical tent of a standard marathon course and a comparison group of
      finishers who did not require intravenous hydration. After giving informed
      consent, subjects had blood drawn and answered a questionnaire regarding fluid
      intake on the course and NSAID use before the race. Blood samples were analyzed
      on-site for serum sodium values as well as other hematologic parameters. RESULTS:
      Fifty-one subjects requiring intravenous hydration as well as 11 subjects who did
      not were enrolled. Three subjects (5.6%; 95% CI, 0-11.9%; missing = 8) in the
      intravenous hydration group had serum sodium less than 130 mEq/L. None of the
      three runners suffered neurologic or pulmonary consequences and only one required
      overnight hospital admission for hydration. The small number of hyponatremic
      subjects precluded the analysis of the role of fluid type or NSAID use in the
      development of hyponatremia or the development of a model for prediction.
      CONCLUSION: This study found a 5.6% incidence of hyponatremia in marathon runners
      requiring medical treatment.

PMID- 11828224
TI  - The effect of exercise, cognitive therapy, and nutritional counseling in treating
      bulimia nervosa.
AB  - OBJECTIVE: The aim of this treatment study on bulimia nervosa was (i) to examine
      the effect of physical exercise as an experimental treatment condition against
      the well-documented effect of cognitive-behavioral therapy (CBT), and (ii) to
      compare the effect of CBT versus the effect of nutritional advice as one single
      treatment component of CBT. METHOD: Normal weight female bulimic patients aged 18
      29 yr were randomly assigned to a physical exercise program (N = 15), CBT (N =
      16), nutritional advice (N = 17), or a waiting list control group (N = 16).
      Seventeen healthy female control subjects were also included. Treatment effects
      were determined by the frequency of binge eating and purging, scores on the
      Eating Disorder Inventory subscales "Drive for thinness," "Bulimia," and "Body
      dissatisfaction" and by a clinical interview to measure symptom severity.
      Assessments were made before and after treatment and at 6- and 18-month follow-up
      after the end of treatment. RESULTS: Nutritional counseling did not prove more
      effective than CBT. Physical exercise appeared more effective than CBT in
      reducing pursuit of thinness; change in body composition; aerobic fitness; and
      frequency of bingeing, purging, and laxative abuse. CONCLUSION: Physical exercise
      is important in the treatment of normal weight bulimic patients. Further studies
      should address possible additive effects of CBT and physical exercise.

PMID- 11828225
TI  - Shorter, more frequent mechanical loading sessions enhance bone mass.
AB  - PURPOSE: The beneficial effects of exercise on bone mass and strength can be
      attributed to the sensitivity of bone cells to mechanical stimuli. However, bone
      cells lose mechanosensitivity soon after they are stimulated. We investigated
      whether the osteogenic response to a simulated high-impact exercise program
      lasting 4 months could be enhanced by dividing the daily protocol into brief
      sessions of loading, separated by recovery periods. METHODS: The right forelimbs
      of adult rats were subjected to 360 load cycles x d(-1), 3 d x wk(-1), for 16 wk.
      On each loading day, one group received all 360 cycles in a single, uninterrupted
      bout (360 x 1); the other group received 4 bouts of 90 cycles/bout (90 x 4), with
      each bout separated by 3 h. After sacrifice, bone mineral content (BMC), and
      areal bone mineral density (aBMD) were measured in the loaded (right) and
      nonloaded control (left) ulnae using DXA. Volumetric BMD (vBMD) and cross
      sectional area (CSA) were measured at midshaft and the olecranon by using pQCT.
      Maximum and minimum second moments of area (I(MAX) and I(MIN)) were measured from
      the midshaft tomographs. RESULTS: After 16 wk of loading, BMC, aBMD, vBMD,
      midshaft CSA, I(MAX), and I(MIN) were significantly greater in right (loaded)
      ulnae compared with left (nonloaded) ulnae in the two loaded groups. When the
      daily loading regimen was broken into four sessions per day (90x4), BMC, aBMD,
      midshaft CSA, and I(MIN) improved significantly over the loading schedule that
      applied the daily stimulus in a single, uninterrupted session (360x1).
      CONCLUSION: Human exercise programs aimed at maintaining or improving bone mass
      might achieve greater success if the daily exercise regime is broken down into
      smaller sessions separated by recovery periods.

PMID- 11828226
TI  - The effects of exercise on children with attention-deficit hyperactivity
      disorder.
AB  - PURPOSE: The effects of exercise on children with attention-deficit hyperactivity
      disorder (ADHD) were evaluated by studying the rate of spontaneous eye blinks,
      the acoustic startle eye blink response (ASER), and motor impersistence among 8-
      to 12-yr-old children (10 boys and 8 girls) meeting DSM-III-R criteria for ADHD.
      METHODS: Children ceased methylphenidate medication 24 h before and during each
      of three daily conditions separated by 24-48 h. After a maximal treadmill walking
      test to determine cardiorespiratory fitness (VO(2peak)), each child was randomly
      assigned to counterbalanced conditions of treadmill walking at an intensity of 65
      75% VO(2peak) or quiet rest. Responses were compared with a group of control
      participants (11 boys and 14 girls) equated with the ADHD group on several key
      variables. RESULTS: Boys with ADHD had increased spontaneous blink rate,
      decreased ASER latency, and decreased motor impersistence after maximal exercise.
      Girls with ADHD had increased ASER amplitude and decreased ASER latency after
      submaximal exercise. CONCLUSIONS: The findings suggest an interaction between sex
      and exercise intensity that is not explained by physical fitness, activity
      history, or selected personality attributes. The clinical meaning of the eye
      blink results is not clear, as improvements in motor impersistence occurred only
      for boys after maximal exercise. Nonetheless, these preliminary findings are
      sufficiently positive to encourage additional study to determine whether a
      session of vigorous exercise has efficacy as a dopaminergic adjuvant in the
      management of behavioral features of ADHD.

PMID- 11828227
TI  - Acute formoterol administration has no ergogenic effect in nonasthmatic athletes.
AB  - PURPOSE: To determine the effect of formoterol (formoterol fumarate dihydrate) on
      the aerobic and anaerobic capacities of highly trained athletes. METHODS: 10 male
      athletes (age = 26.2 +/- 0.9, VO(2max) = 65.6 +/- 2.4 mL x kg(-1) x min(-1)) with
      minimal bronchial reactivity to aerosols (i.e., negative methacholine challenge
      test) completed three identical exercise sessions differing only by the
      medication administered. Formoterol (F) a long-acting beta(2)-agonist, presently
      not approved for international competition by the I.O.C. Medical committee, was
      compared with salbutamol (S), an accepted bronchodilator, and a placebo (P).
      Formoterol (12 microg), salbutamol (400 microg), or placebo was administered by a
      Turbuhaler, 10 min before exercise testing in a double-blind, randomized, three
      way crossover design. Testing sessions included a Wingate anaerobic test followed
      15 min later by an incremental cycle ergometer test to exhaustion. RESULTS: There
      were no significant differences between the groups in VO(2max) (F = 66.5 +/- 2.7;
      S = 67.8 +/- 2.5; P = 67.5 +/- 2.1 mL x kg(-1) x min(-1)) or Wingate peak power
      (F = 885 +/- 40; S = 877 +/- 40; P = 885 +/- 44 W) values. During the maximal
      aerobic test, no differences were observed in maximum minute ventilation,
      respiratory exchange ratio, heart rate, or work between the three experimental
      conditions. Also, there were no differences in the Wingate anaerobic test
      variables, total work, or fatigue index. CONCLUSION: Formoterol, administered in
      one aerosolized therapeutic dose, does not have an ergogenic effect in elite
      athletes without asthma.

PMID- 11828228
TI  - Hereditary thrombophilia in elite athletes.
AB  - PURPOSE: Although under normal circumstances exercise prevents thrombosis, there
      are cases in the literature that indicate a connection between exercise and the
      onset of thrombosis. In the average population, hereditary thrombophilia is a
      major cause of thrombosis. However, nothing is known about the prevalence of
      hereditary thrombophilia in elite athletes. Because high-performance sports are
      known to carry an increased risk of thrombogenesis, measures to avoid thrombosis
      must be initiated in cases of known hereditary thrombophilia. METHODS: Hereditary
      thrombophilia was checked for in 173 elite athletes, members of the German
      national team. Antithrombin III, protein C, protein S, and the APC ratio,
      followed by a molecular genetic analysis, were measured, and molecular analysis
      of factor II G20210A mutation was used to detect the presence of an antithrombin
      III-, protein C- and protein S-deficiency, as well as factor V Leiden (factor V
      506Arg to Gln) and factor II G20210A mutation. RESULTS: No definite antithrombin
      III-, protein C- or protein S-deficiency was found. In 12 cases, an APC
      resistance caused by a factor V Leiden mutation (11 heterozygous; 1 homozygous)
      was detected. In 10 cases, a heterozygous factor II G20210A was observed; a
      combination of both mutations was not found. For factor V Leiden, this
      corresponds to a prevalence of 6.9% (CI 95% 3.6-11.8%) in our group, similar to
      prevalence rates in the general population. Additionally, the observed prevalence
      of 5.8% (CI 95% 2.8-10.4%) of factor II G20210A is nearly within the range as
      reported by several authors. CONCLUSION: Based on the observed prevalence of APC
      resistance and factor II G20210A mutation in our group of athletes, along with
      consideration of additional circumstantial risks, screening tests for elite
      athletes should be considered to allow the undertaking of preventive measures.

PMID- 11828229
TI  - Diagnosing external iliac endofibrosis by postexercise ankle to arm index in
      cyclists.
AB  - PURPOSE: The aim of this study was to determine a noninvasive method of
      evaluating external iliac endofibrosis in cyclists. METHODS: Eighteen highly
      trained male cyclists were divided into two groups: a pathology group (PG; 3
      professional and 4 elite) and a control group (CG; 6 professional and 5 elite).
      Mean age was 26 +/- 6.1 yr for the PG and 24 +/- 4.09 for the CG. We studied
      humeral and tibial posterior pressure by using Doppler ultrasound and the ankle
      to arm index (AAI) before and after an incremental exercise test, performed on
      bike-ergometer until exhaustion. A Wilcoxon test was used to compare pressures
      and AAI in the PG. A Mann-Whitney test was used to compare the PG with the CG.
      Fisher discriminant analysis was done to obtain a classification of the legs in
      ill or normal legs. RESULTS: The minimal AAI achieved in the PG was 0.76 +/- 0.13
      for the normal leg (NL) and 0.35 +/- 0.04 for the ill leg (IL). We found
      significant differences (P < 0.01) from the 1st to 4th minute after exercise
      between the NL and the IL in the PG, and from the 1st to 10th minute after
      exercise between the IL and CG. We found significant differences in leg pressures
      between NL and IL in PG from the 1st to 4th minute (P < 0.01), and from the 1st
      to the 10th minute after exercise between CG and IL in the PG. Through
      discriminant analysis, we obtained a classification of the legs as ill or normal
      by applying a mathematical function at each recovery time studied. CONCLUSIONS:
      AAI and leg pressures response to maximal exercise is a valid and noninvasive
      method for the evaluation of external iliac endofibrosis.

PMID- 11828230
TI  - Physical activity and the presence and extent of calcified coronary
      atherosclerosis.
AB  - PURPOSE: Regular physical activity leads to a more favorable cardiovascular risk
      factor profile and a lower risk of developing incident coronary heart disease
      (CHD). These correlations suggest that higher levels of physical activity should
      also attenuate the presence and extent of coronary atherosclerosis. METHODS:
      Physical activity was measured using the Baecke Physical Activity Index in 630
      consecutive asymptomatic men and women ages 39-45 without known heart disease.
      The degree of physical activity was compared with the cardiovascular risk factor
      profile and the presence and extent of subclinical atherosclerosis measured using
      electron beam computed tomography. RESULTS: Sports-related physical activity was
      associated with lower body mass index (r = -0.11; P = 0.001), higher high-density
      lipoprotein (HDL) cholesterol (r = 0.13; P = 0.003) and less glucose resistance
      as assessed by fasting serum insulin levels (r = -0.16; P = 0.001). Leisure-time
      and work-related physical activity were unrelated to any coronary risk variables.
      Calcified subclinical atherosclerosis was unrelated to all physical activity
      dimensions. Comparing the most sedentary (lowest quartile) and most active
      (highest quartile) patients, the prevalence of coronary calcium (17.0% vs 18.5%;
      P = 0.92) and mean coronary calcium scores (8 +/- 31 vs 5 +/- 15; P = 0.87) were
      similar. In a multivariate model controlling for standard cardiovascular risk
      factors and physical activity level, only low-density lipoprotein (LDL)
      cholesterol was associated with the presence of coronary calcium. CONCLUSION:
      Physical activity, particularly high-intensity exercise in sports-related
      activities, promotes a healthy cardiovascular risk profile, including lower body
      mass index and insulin resistance, but is unrelated to coronary calcification.
      This suggests that the risk reduction associated with physical activity is
      mediated by factors other than retarding the development of calcified
      atherosclerosis.

PMID- 11828231
TI  - Commuting, leisure-time physical activity, and cardiovascular risk factors in
      China.
AB  - PURPOSE: The relationship between both commuting and leisure-time physical
      activity and selected cardiovascular risk factors was analyzed. METHODS: A cross
      sectional survey was carried out in 1996 in urban Tianjin, China. A total of 2002
      male and 1974 female subjects aged 15-69 yr completed the survey. Commuting,
      leisure-time physical activity, body mass index, blood pressure, and cigarette
      smoking were determined. RESULTS: Doing more than 60 min of commuting physical
      activity or combined commuting and leisure-time physical activity was related to
      the highest mean blood pressure and the highest prevalence of hypertension among
      both genders compared with going to and from work by bus; 31-60 min commuting
      only or commuting plus leisure-time physical activity was associated with the
      lowest mean blood pressure in women and the lowest prevalence of hypertension in
      both genders. Daily time on commuting or leisure-time physical activity was
      inversely related to mean body mass index and prevalence of overweight among men
      and prevalence of smoking among both genders. CONCLUSION: The present study
      suggests that commuting and leisure-time physical activity were favorably
      associated with cardiovascular risk factors in this Chinese population, except
      that more than 60 min of physical activity was associated with high blood
      pressure.

PMID- 11828232
TI  - Screening, staffing, and emergency preparedness at worksite wellness facilities.
AB  - PURPOSE: The purpose of this survey was to examine compliance of worksite health
      and fitness facilities with the American Heart Association/American College of
      Sports Medicine (AHA/ACSM) recommendations for cardiovascular screening,
      staffing, and emergency policies for health and fitness facilities. METHODS: A
      survey was developed and sent to 529 worksite health and fitness facilities.
      RESULTS: A total of 221 surveys were returned (42% response rate). Twelve percent
      of facilities had no staff supervision. Among facilities with staff, 12% were not
      certified in basic life support, and 6% had no national professional
      certification. Ninety-two percent of facilities followed a health history
      screening policy although 13% of these facilities administered it irregularly or
      not at all. Of a total 187 responding facilities, 122 (65%) defined "at risk" as
      two or more risk factors for heart disease. Of these, 97% either required or
      recommended new members obtain physician clearance before participation. Four
      (3%) responding facilities did not require physician clearance. Twenty-five
      percent of facilities experienced at least one emergency that required ambulance
      support in the previous year. CONCLUSION: Although this was a low response rate,
      most responding worksite health and fitness facilities appear to be in compliance
      with the AHA/ACSM recommendations yet have inconsistencies in some specific
      practices. There appears to be a need for further consistent implementation of
      these recommendations into worksite settings.

PMID- 11828233
TI  - Effect of weight loss on T-cell receptor-mediated T-cell function in elite
      athletes.
AB  - PURPOSE: Long-term intensive exercise by athletes may sometimes lead to a
      susceptibility to infections. In the present study, we examined the differences
      in immune function between amateur wrestlers experiencing weight loss (WL) and
      those without WL who underwent similar intensive exercise training. METHODS:
      Eighteen elite amateur wrestlers who attended the Japanese national championship
      were classified into two groups. One group consisted of those with either slight
      or no WL (without WL) (<4%; mean, 1%) (N = 9), and the other group consisted of
      those who needed a significant WL (with WL) (> or = 4%; mean, 7%) (N = 9) during
      a 1-month period of intensive training. The leukocyte counts as well as the
      leukocyte subsets in the peripheral blood were examined. The proliferation and
      cytokine production in T lymphocytes in response to bacterial superantigens
      (staphylococcal enterotoxin B, streptococcal pyrogenic exotoxin A) and anti-CD3
      antibody (Ab) were also examined. RESULTS: The total leukocyte counts and
      leukocyte subsets did not differ substantially between the groups and were also
      not different from the findings before starting the intensive exercise training.
      Natural killer cells and T cells among the lymphocytes significantly increased in
      both groups, whereas the increase in each group was not different. Although the T
      cell responses to bacterial superantigens were not different, the anti-CD3 Ab
      stimulated proliferation and interferon-gamma production of lymphocytes from the
      wrestlers with WL were significantly lower than those of the wrestlers without
      WL. This hyporesponsiveness to CD3 stimulation recovered 2 months after the
      tournament when the wrestlers reverted to their normal weight. CONCLUSION:
      Intensive exercise in athletes accompanied by a rapid WL was found to compromise
      the CD3/T-cell receptor-mediated T-cell function in athletes.

PMID- 11828234
TI  - Diaphragm plasticity following intrinsic laryngeal muscle denervation in rats.
AB  - PURPOSE: During inspiration, recruitment of the intrinsic laryngeal muscles (ILM)
      reduces the inspiratory load on the ventilatory pump muscles. The purpose of our
      study was to determine 1) whether the diaphragm adapts to denervation of the ILM,
      and 2) whether the additional stimulus of exercise training affects the degree to
      which the diaphragm adapts to ILM denervation. METHODS: Thirty-six male Sprague
      Dawley rats (2 months) were randomly divided into sedentary control (SC),
      sedentary-denervated (SD), and exercise-denervated (ED) groups. Control animals
      underwent sham operations, whereas ILM-denervated animals underwent bilateral
      transection of the recurrent laryngeal nerves. Three weeks after surgery, animals
      in the ED group performed a treadmill training protocol for a period of 6 wk.
      RESULTS: Denervation (SD and ED animals) of the ILM significantly increased
      diaphragm citrate synthase activity (20%), in vitro endurance, and time to peak
      twitch tension (15%), and reduced (13%) peak tetanic tension (Po, N x cm(-2)). No
      independent training effect over and above the effects attributed to denervation
      of ILM were noted in ED animals. CONCLUSION: The results highlight the role of
      vocal cord dilator function during both eupnea and exercise-induced hyperpnea.

PMID- 11828235
TI  - Capillarization in skeletal muscle of rats with cardiac hypertrophy.
AB  - PURPOSE: Exercise intolerance during chronic heart failure (CHF) is localized
      mainly in skeletal muscle. A decreased capillarization may impair exchange of
      oxygen between capillaries and muscle tissue and in this way contribute to
      exercise intolerance. We assessed changes in capillary supply in plantaris and
      diaphragm muscles of a rat aorta-caval fistula (ACF) preparation, a volume
      overload model for CHF. METHODS: An ACF was created under equithesin anesthesia.
      Plantaris and diaphragm muscles were removed 6 wk postsurgery and examined for
      myosin heavy chain (MyHC) content and capillary supply. RESULTS: Cardiac
      hypertrophy was 96% (P < 0.002) after ACF. The Type IIb MyHC content of the
      plantaris muscles increased (33.9 +/- 3.3 vs 49.8 +/- 3.8%; mean +/- SEM) at the
      expense of Type IIa MyHC (17.6 +/- 1.8 vs 11.2 +/- 1.7%) in ACF rats (P < 0.05).
      In the diaphragm, the number of Type I (32.1 +/- 2.3 vs 40.6 +/- 2.7%) and IIb
      fibers (40.6 +/- 1.9 vs 49.6 +/- 3.6%) increased at the expense of Type IIa
      fibers (26.8 +/- 2.5 vs 9.4 +/- 0.9%) (P < 0.05). The capillary number per fiber
      did not change, and this indicated that no capillary loss occurred with ACF.
      Also, the capillary density was maintained in the diaphragm and plantaris muscles
      of ACF rats. Furthermore, the coupling between fiber type, size, and metabolic
      type of surrounding fibers, with the capillary supply to a fiber, was maintained
      in rats with an ACF. CONCLUSION: The cardiac hypertrophy induced by volume
      overload seems adequate to prevent atrophy and changes in the microcirculation of
      limb and diaphragm muscles.

PMID- 11828236
TI  - Inhibited longitudinal growth of bones in young male rats by clenbuterol.
AB  - PURPOSE: Clenbuterol is one of the beta-2 adrenergic receptor agonists with
      potent anabolic properties in muscles, yet the concomitant effects on muscle and
      bone in young animals remain to be resolved. Therefore, the purpose of this study
      was to determine the effects of clenbuterol administration on muscles and bones
      of young rats. METHODS: Twelve male Sprague-Dawley rats (9-wk-old) were randomly
      assigned to either a control (CON, N = 6) or clenbuterol group (CLE, N = 6).
      Clenbuterol of 2 mg x kg body wt x d(-1) was administered subcutaneously for 4
      wk. After treatment, the soleus (SOL), extensor digitorum longus (EDL), and
      ventricle (VENT) muscles and the femurs (FE) and tibiae (TI) bones were excised
      and analyzed. The bone mineral content (BMC), area, and bone mineral density
      (BMD) of FE and TI were measured by dual-energy x-ray absorptiometry (DXA). The
      longitudinal lengths of bones were measured with the Vernier calipers. RESULTS:
      CLE showed smaller body weight than CON (P < 0.05) after the treatment. The
      muscle wet weights in CLE tended (P = 0.08) to be higher than CON in SOL (9%) and
      EDL (12%), but the ratio of muscle wet weight-to-body weight were higher (SOL: P
      < 0.05, EDL: P < 0.01) than CON. VENT of CLE showed increases in both the wet
      weight and the ratio (P < 0.01). FEs in CLE showed smaller values in BMC (P <
      0.01), area (P < 0.01), and length (P < 0.05) than CON but not in BMD. TIs showed
      significant decreases (P < 0.01) in BMC, area, and length but not in BMD.
      CONCLUSION: These results indicated that clenbuterol induced the muscular
      hypertrophy but inhibited the longitudinal growth of bones in young male rats,
      which may be a serious concern in any ergogenic use.

PMID- 11828237
TI  - Desmin characteristics of CD11b-positive fibers after eccentric contractions.
AB  - PURPOSE: The purpose of this study was to determine the desmin characteristics of
      fibers infiltrated by CD11b-leukocytes in fast- and slow-twitch murine muscles
      after eccentric contractions. METHODS: We developed a computer image analysis
      procedure to quantify the percentage of intramyofiber CD11b-leukocyte
      infiltration. Only CD11b-positive fibers that exhibited identifiable borders were
      examined. Patterns of leukocyte infiltration of these fibers were distinguished
      and confirmed quantitatively by determining the mean percentage of leukocyte
      infiltration. We examined the desmin characteristics of these fibers with the
      same image analysis system and quantified the percentage of the fiber that
      demonstrated antidesmin staining. The influence of sex and muscle type on desmin
      characteristics and percentage of CD11b-leukocyte infiltration also was analyzed.
      RESULTS: The percentage of CD11b-leukocyte infiltration was less than 50% for the
      majority of fibers. Three intramyofiber leukocyte infiltration patterns were
      identified that had significantly different mean percentages of leukocyte
      infiltration: 14%, 27%, and 47% (P < 0.001). Of the three desmin characteristics
      (normal, increased, and decreased) that were observed, almost three fourths of
      the fibers exhibited increased desmin. A significant difference in the percentage
      of increased desmin was found among the CD11b-leukocyte infiltration patterns (P
      = 0.01). Fibers with the least amount of CD11b-leukocyte infiltration showed the
      greatest amount of increased desmin. Sex and muscle type did not influence any of
      these findings. CONCLUSION: Increased desmin appears to be associated with an
      early stage of intramyofiber leukocyte infiltration after eccentric contractions.

PMID- 11828238
TI  - Effects of clothing on accuracy and reliability of air displacement
      plethysmography.
AB  - PURPOSE: The purpose of this investigation was to quantify the effects of
      different attire on the accuracy and reliability of estimating percent body fat
      (%fat) by using air displacement plethysmography (ADP). METHODS: Fifteen adults
      were tested four times on four separate occasions. Each session consisted of
      estimating %fat with ADP wearing a swimsuit (ADP(SS)), a hospital gown (ADP(HG)),
      and in the nude (ADP(N)), plus assessment by hydrostatic weighing (HW). RESULTS:
      An ANOVA revealed no significant differences within any of the four methods over
      the 4 days. Intraclass correlation coefficients revealed a strong relationship
      for repeated measures in ADP(SS) (r = 0.981), ADP(HG) (r = 0.993), ADP(N) (r =
      0.989), and HW (r = 0.976). Mean data for each condition indicated a significant
      underestimation (P < 0.05) of %fat while wearing a hospital gown (13.8 +/- 7.7%)
      compared with ADP(SS) (22.0 +/- 7.8%), ADP(N) (23.5 +/- 7.5%), and HW (22.6 +/-
      6.8%). CONCLUSION: Reliability of ADP does not appear to be compromised by
      clothing; however, wearing a hospital gown significantly affects accuracy,
      reducing %fat estimations by approximately 9% compared with the recommended
      swimsuit. Measurement in the nude does not provide more reliable or accurate
      measures than wearing a swimsuit.

PMID- 11828239
TI  - Bone mineral density in adolescent female athletes: relationship to exercise type
      and muscle strength.
AB  - PURPOSE: This study investigated the influence of different exercise types and
      differences in anatomical distribution of mechanical loading patterns on bone
      mineral density (BMD) in elite female cyclists, runners, swimmers, triathletes,
      and controls (N = 15 per group). Associations between leg strength and BMD were
      also examined. METHODS: Areal BMD (g x cm(-2)) was assessed by duel-energy x-ray
      absorptiometry (DXA) (total body (TB), lumbar spine (LS), femoral neck (FN),
      legs, and arms). Right knee flexion and extension strength was measured using a
      Cybex Norm isokinetic dynamometer at 60 degrees x s(-1). RESULTS: Runners had
      significantly higher unadjusted TB, LS, FN, and leg BMD than controls (P < 0.05);
      higher TB, FN, and leg BMD than swimmers (P < 0.05); and greater leg BMD than
      cyclists (P < 0.05). Absolute knee extension strength was significantly (P <
      0.01) correlated (0.33 < or = r < or = 0.44) with TB, FN, LS, and leg BMD for all
      groups combined. Weaker but still significant correlations (0.28 < or = r < or =
      0.33) existed for normalized (per leg lean tissue mass) knee extension strength
      and all BMD sites, except FN BMD. There were no significant correlations between
      absolute or normalized knee flexion strength and any of the BMD variables.
      Absolute knee extension strength was entered as the second independent predictor
      for LS and leg BMD in stepwise multiple linear regression analysis (MLRA),
      accounting for increments of 4% and 12%, respectively, in total explained
      variation. CONCLUSION: We conclude that running, a weight bearing exercise, is
      associated with larger site-specific BMD than swimming or cycling, that the
      generalized anatomical distribution of loads in triathlon appears not to
      significantly enhance total body BMD status, and that knee extension strength is
      only a weak correlate and independent predictor of BMD in adolescent females.

PMID- 11828240
TI  - Ethnic differences in titratable acid excretion and bone mineralization.
AB  - PURPOSE: To test our hypothesis that differences in urinary calcium excretion
      among blacks and whites may be secondary to ethnic variations in acid (H(+))
      metabolism and to prove that increases in titratable acid excretion would be
      found among individuals predisposed to the development of stress fractures.
      METHODS: We administered 8 g NH(4)Cl acutely to 11 black and 18 white healthy
      volunteers and measured urinary sodium, calcium, and acid excretions. We measured
      the Na(+)/H(+) antiporter activity using acid-loaded platelets as surrogate
      markers for this exchanger expressed in renal epithelial cells. We also compared
      differences in titratable acid excretion among a cohort of subjects with, and
      without, a history of stress fracture. RESULTS: NH(4)Cl-induced increases in
      titratable urinary acid correlated with changes in the renal excretion of calcium
      and sodium, and stimulated acid excretion correlated with basal acid loss.
      Despite comparable changes in plasma pH, whites, when compared to blacks, had
      much greater basal acid excretion and NH(4)Cl-induced acid excretion. Whites also
      had much greater baseline calcium excretion rates when compared to blacks.
      Following acid loading, whites continued to exhibit greater calcium excretion
      rates than blacks. Acid loading significantly decreased sodium excretion in
      whites but not in blacks. Blacks also had significantly attenuated Na(+)/H(+)
      exchange activity. In a cohort of resting, athletic students, we found enhanced
      basal H(+) and phosphate excretion among subjects who experienced stress
      fractures during their rigorous physical training when compared to those
      individuals who did not. CONCLUSION: Blacks may have a greater endogenous
      buffering capacity than whites, or the reported ethnic differences in sodium and
      calcium excretion rates between blacks and whites may be secondary to racial
      variations in renal H(+) excretion. We conclude that both ethnic differences in
      bone mineralization and bone integrity in athletes are mediated by heritable
      differences in titratable acid excretion.

PMID- 11828241
TI  - Resistance training preserves skeletal muscle function during unloading in
      humans.
AB  - PURPOSE: The intent of this investigation was to design and evaluate a low
      volume, high-intensity resistance-training program to preserve knee extensor (KE)
      and plantar flexor (PF) size as measured by cross-sectional area (CSA), strength,
      and neuromuscular function (IEMG) with unloading. METHODS: Thirty-two men (age =
      30 +/- 3 yr; weight = 80 +/- 4 kg; height = 181 +/- 2 cm) participated. Sixteen
      men underwent 21 d of unilateral lower-limb suspension (ULLS) and were assigned
      to control (ULLS-CON, N = 8) or countermeasures (ULLS-CM, N = 8). The remaining
      subjects were ambulatory for 21 d and were assigned to control (AMB-CON, N = 8)
      or countermeasures (AMB-CM, N = 8). Countermeasure subjects performed resistance
      training every third day during the 21-d period. RESULTS: KE and PF CSA decreased
      (P < 0.05) 7% in the ULLS-CON, whereas no changes occurred in ULLS-CM, AMB-CON,
      and AMB-CM. ULLS-CON maximal voluntary contraction (MVC) decreased 17% (P < 0.05)
      in the KE and PF. ULLS-CON torque-velocity characteristics (concentric and
      eccentric) decreased (P < 0.05), 22% to 12% and 20% to 14% (slow to fast) in the
      KE and PF, respectively. ULLS-CM PF increased (P < 0.05) in MVC and eccentric
      contractions, whereas no other changes occurred in MVC or torque-velocity
      characteristics in the KE or PF of the ULLS-CM, AMB-CON, and AMB-CM subjects.
      Submaximal IEMG increased (P < 0.05) whereas maximal IEMG decreased (P < 0.05) in
      the KE and PF of the ULLS-CON group. However, no change or slight improvements in
      IEMG activity were found in the KE and PF of the ULLS-CM, AMB-CON, and AMB-CM.
      CONCLUSION: These results indicate that a resistance-training paradigm employed
      every third day during 21 d of unloading was effective in maintaining skeletal
      muscle strength (static and dynamic) and size of the KE and PF.

PMID- 11828242
TI  - "Pumped-up propulsion" during front crawl swimming.
AB  - PURPOSE: It is currently held that propulsion in human front crawl swimming is
      achieved by lift and drag forces predominantly generated by the hands.
      Calculation of these propulsive forces relies on the quasi-steady assumption that
      the fluid dynamic behavior of a hand model in a flow channel (constant velocity
      and orientation) is similar to that of a hand of a real swimmer. However, both
      experimental and theoretical analyses suggest that this assumption is
      questionable and that unsteady and rotational propulsion mechanisms play a
      significant role. Theoretical considerations suggest that arm rotation could lead
      to a proximodistal pressure gradient, which would induce significant axial flow
      along the arm toward the hand. METHODS: To gain insight into such mechanisms, we
      used tufts to study the flow directions around the arm and hand during the front
      crawl, which consists of a glide, an insweep, and an outsweep phase. In a second
      experiment, we measured pressure during the stroke at various points along the
      arm and hand. RESULTS: It was observed that 1) the flow during insweep and part
      of the outsweep was highly unsteady; 2) the arm movements were largely
      rotational; 3) a clear axial flow component, not in the direction of the arm
      movement, was observed during insweep and outsweep; and 4) both the V-shaped
      "contracting" arrangement of the tufts during the outsweep and pressure
      recordings point to a pressure gradient along the direction of the arm during the
      outsweep, as predicted on theoretical grounds. CONCLUSION: Our results
      demonstrate the reality of the predicted rotational and unsteady effects during
      front crawl swimming. We hypothesize that the axial flow observed during the
      outsweep has a propulsion-enhancing effect by increasing the pressure difference
      over the hand. Further investigation is required to establish more accurately the
      role of axial flow on propulsion.

PMID- 11828243
TI  - Kinetics of VO(2) in professional cyclists.
AB  - PURPOSE: To analyze the kinetics of oxygen uptake (VO(2)) in professional road
      cyclists during a ramp cycle ergometer test and to compare the results with those
      derived from well-trained amateur cyclists. METHODS: Twelve professional cyclists
      (P group; 25 +/- 1 yr; maximal power output (W(max)), 508.3 +/- 9.3 watts) and 10
      amateur cyclists (A group; 22 +/- 1 y; W(max), 429.9 +/- 8.6 watts) performed a
      ramp test until exhaustion (power output increases of 25 watts x min(-1)). The
      regression lines of the VO(2):power output (W) relationship were calculated for
      the following three phases: phase I (below the lactate threshold (LT)), phase II
      (between LT and the respiratory compensation point (RCP)), and phase III (above
      RCP). RESULTS: In group P, the mean slope (Delta VO(2):Delta W) of the VO(2):W
      relationship decreased significantly (P < 0.01) across the three phases (9.9 +/-
      0.1, 8.9 +/- 0.2, and 3.8 +/- 0.6 mL O(2) x watts(-1) x min(-1) for phases I, II,
      and III, respectively). No significant differences (P > 0.05) were found between
      phases I and II (P > 0.05) in group A, whereas Delta VO(2):Delta W significantly
      increased in phase III (P < 0.01), compared with phase II (10.2 +/- 0.3, 9.2 +/-
      0.4, and 10.1 +/- 1.1 mL O(2) x watts(-1) x min(-1) in phases I, II, and III,
      respectively). The mean value of Delta VO(2):Delta W for phase III was
      significantly lower in group P than in group A (P < 0.01). CONCLUSION: Contrary
      to the case in amateur riders, the rise in VO(2) in professional cyclists is
      attenuated at moderate to high workloads. This is possibly an adaptation to the
      higher demands of their training/competition schedule.

PMID- 11828244
TI  - Determinants of VO(2) kinetics at high power outputs during a ramp exercise
      protocol.
AB  - PURPOSE: To determine the relationship between the additional, nonlinear increase
      in oxygen uptake (Delta VO(2)) that occurs at high power outputs during a ramp
      cycle ergometer test, on one hand; and possible explanatory mechanisms of the
      phenomenon, such as cardiorespiratory work, blood lactate, fitness level, or
      muscle fiber distribution, on the other. METHODS: Ten healthy, sedentary young
      adults (age (mean +/- SEM), 22 +/- 1 yr) were chosen as subjects. A muscle biopsy
      specimen was taken from the vastus lateralis of the right leg to determine fiber
      type distribution by immunohistochemical identification of myosin heavy chain
      (MHC) isoforms. During the ramp tests (power output increases of 5 W every 15-s
      interval), the ventilatory threshold (VT) and lactate threshold (LT) were
      measured. We defined Delta VO(2) as the difference between "true" VO(2) values
      observed at the maximal power output (VO(2)obs) and those expected (VO(2)exp)
      from the previous linear VO2:power output relationship below the VT. RESULTS: A
      nonlinear increase was observed in VO2 (Delta VO(2) = 239 +/- 79 mL x min(-1), P
      < 0.05 for VO(2)obs vs VO(2)exp), which was significantly correlated with the
      percentage of type IIX fibers (r = 0.80, P < 0.05). No other correlations were
      found between Delta VO(2) and possible explanatory mechanisms. CONCLUSION: A
      greater percentage of type IIX fibers is associated with a higher excess VO(2) at
      high power outputs (above VT).

PMID- 11828245
TI  - Effects of creatine supplementation on muscle power, endurance, and sprint
      performance.
AB  - PURPOSE: To determine the effects of creatine (Cr) supplementation (20 g x d(-1)
      during 5 d) on maximal strength, muscle power production during repetitive high
      power-output exercise bouts (MRPB), repeated running sprints, and endurance in
      handball players. METHODS: Nineteen trained male handball players were randomly
      assigned in a double-blind fashion to either creatine (N = 9) or placebo (N = 10)
      group. Before and after supplementation, subjects performed one-repetition
      maximum half-squat (1RM(HS) and bench press (1RM(BP)), 2 sets of MRPB consisting
      of one set of 10 continuous repetitions (R10) followed by 1 set until exhaustion
      (R(max)), with exactly 2-min rest periods between each set, during bench-press
      and half-squat protocols with a resistance equal to 60 and 70% of the subjects'
      1RM, respectively. In addition, a countermovement jumping test (CMJ) interspersed
      before and after the MRPB half-squat exercise bouts and a repeated sprint running
      test and a maximal multistage discontinuous incremental running test (MDRT) were
      performed. RESULTS: Cr supplementation significantly increased body mass (from
      79.4 +/- 8 to 80 +/- 8 kg; P < 0.05), number of repetitions performed to fatigue,
      and total average power output values in the R(max) set of MRPB during bench
      press (21% and 17%, respectively) and half-squat (33% and 20%, respectively), the
      1RM(HS) (11%), as well as the CMJ values after the MRPB half-squat (5%), and the
      average running times during the first 5 m of the six repeated 15-m sprints (3%).
      No changes were observed in the strength, running velocity, or body mass measures
      in the placebo group during the experimental period. CONCLUSION: Short-term Cr
      supplementation leads to significant improvements in lower-body maximal strength,
      maximal repetitive upper- and lower-body high-power exercise bouts, and total
      repetitions performed to fatigue in the R(max) set of MRPB, as well as enhanced
      repeated sprint performance and attenuated decline in jumping ability after MRPB
      in highly trained handball players. Cr supplementation did not result in any
      improvement in upper-body maximal strength and in endurance running performance.

PMID- 11828247
TI  - Age and gender differences in objectively measured physical activity in youth.
AB  - PURPOSE: The purpose of this study was to evaluate age and gender differences in
      objectively measured physical activity (PA) in a population-based sample of
      students in grades 1-12. METHODS: Participants (185 male, 190 female) wore a CSA
      7164 accelerometer for 7 consecutive days. To examine age-related trends,
      students were grouped as follows: grades 1-3 (N = 90), grades 4-6 (N = 91),
      grades 7-9 (N = 96), and grades 10-12 (N = 92). Bouts of PA and minutes spent in
      moderate-to-vigorous PA (MVPA) and vigorous PA (VPA) were examined. RESULTS:
      Daily MVPA and VPA exhibited a significant inverse relationship with grade level,
      with the largest differences occurring between grades 1-3 and 4-6. Boys were more
      active than girls; however, for overall PA, the magnitudes of the gender
      differences were modest. Participation in continuous 20-min bouts of PA was low
      to nonexistent. CONCLUSION: Our results support the notion that PA declines
      rapidly during childhood and adolescence and that accelerometers are feasible
      alternatives to self-report methods in moderately sized population-level
      surveillance studies.

PMID- 11828246
TI  - Effect of ingesting caffeine and ephedrine on 10-km run performance.
AB  - BACKGROUND: The ingestion of either caffeine (C) or ephedrine (E) has been shown
      to improve performance during high-intensity aerobic activity lasting 10-20 min,
      with an additive effect being found when the combination (C + E) was ingested. It
      was the purpose of this study to determine if the addition of E to C would
      improve performance in activity lasting longer than 20 min. METHODS: One and one
      half hours after ingesting a placebo (P), C (4 mg/kg), E (0.8 mg/kg), or C + E,
      12 subjects performed a 10-km run while wearing a helmet and backpack weighing 11
      kg. The trials were performed in a climatic suite at 12-13 degrees C, on a
      treadmill where the speed was regulated by the subject. VO(2), VCO(2), V(E),
      heart rate (HR), and rating of perceived exertion (RPE) were measured during the
      run at 15 and 30 min, and again when the individual reached 9 km. Blood was
      sampled at 15 and 30 min and again at the end of the run and assayed for lactate,
      glucose, and catecholamines. RESULTS: Run times (mean +/- SD), in minutes, were
      for C (46.0 +/- 2.8), E (45.5 +/- 2.9), C + E (45.7 +/- 3.3), and P (46.8 +/-
      3.2). The run times for the E trials (E and C + E) were significantly reduced
      compared with the non-E trials (C and P). Pace was increased for the E trials
      compared with the non-E trials over the last 5 km of the run. VO(2) was not
      affected by drug ingestion. HR was elevated for the ephedrine trials (E and C +
      E). RPE remained similar for all trails. Caffeine increased the epinephrine and
      norepinephrine response associated with exercise and also increased blood
      lactate, glucose, and glycerol levels. Ephedrine reduced the epinephrine response
      but increased dopamine and FFA levels. CONCLUSION: The previously seen additive
      nature of E and C was not evident in this study, with the primary ergogenic
      effect being attributed to E.

PMID- 11828248
TI  - Comparison of the physical fitness of men and women entering the U.S. Army: 1978
      1998.
AB  - PURPOSE: To compare the physical fitness levels of recruits entering the U.S.
      Army in 1998 to those entering in 1978 and 1983. METHODS: In 1998, 182 men and
      168 women were tested before beginning basic training at Fort Jackson, SC. The
      measurements were 1) skin-fold estimation of percent body fat (%BF); 2) maximum
      oxygen uptake by treadmill running (VO2max); and 3) upper-body (UB), lower-body
      (LB), and upright pulling (UP) isometric strength. These data were compared to
      data from basic trainees at Fort Jackson in 1978 (skin folds, VO2max, UB, and LB)
      and 1983 (skin folds and UP). RESULTS: Body weight (BW) of 1998 recruits was
      greater (P < 0.05) than 1978 recruits (men, 12%; women, 6%) and 1983 recruits
      (men, 8%; women, 7%). %BF of 1998 recruits was greater (P < 0.05) than 1978
      recruits (men, 15%; women, 5%) and 1983 recruits (men, 15%; women, 17%). The 1998
      men had more fat-free mass (FFM) (P < 0.05) than men in 1978 (8%) or 1983 (5%),
      whereas 1998 women were only different from those measured in 1978 (4%, P <
      0.05). The VO2max of men (50.6 +/- 6.2 mL x kg(-1) x min(-1)) was equivalent to
      men in 1978, whereas that of women (39.7 +/- 5.2 mL x kg(-1) x min(-1)) was 6%
      greater (P < 0.05). The 1998 recruits were stronger (P < 0.05) on all measures of
      muscle strength than recruits measured in 1978 (men, UB = 16%, LB = 12%; women,
      UB = 18%, LB = 6%) and 1983 (men, UP = 7%; women, UP = 6%). CONCLUSION: The
      aerobic capacity, muscle strength, and FFM of 1998 recruits is comparable to or
      greater than that of 1978 and 1983 recruits; however, 1998 recruits tended to
      have more BW and a greater %BF.

PMID- 11828249
TI  - American College of Sports Medicine position stand. Progression models in
      resistance training for healthy adults.
AB  - In order to stimulate further adaptation toward a specific training goal(s),
      progression in the type of resistance training protocol used is necessary. The
      optimal characteristics of strength-specific programs include the use of both
      concentric and eccentric muscle actions and the performance of both single- and
      multiple-joint exercises. It is also recommended that the strength program
      sequence exercises to optimize the quality of the exercise intensity (large
      before small muscle group exercises, multiple-joint exercises before single-joint
      exercises, and higher intensity before lower intensity exercises). For initial
      resistances, it is recommended that loads corresponding to 8-12 repetition
      maximum (RM) be used in novice training. For intermediate to advanced training,
      it is recommended that individuals use a wider loading range, from 1-12 RM in a
      periodized fashion, with eventual emphasis on heavy loading (1-6 RM) using at
      least 3-min rest periods between sets performed at a moderate contraction
      velocity (1-2 s concentric, 1-2 s eccentric). When training at a specific RM
      load, it is recommended that 2-10% increase in load be applied when the
      individual can perform the current workload for one to two repetitions over the
      desired number. The recommendation for training frequency is 2-3 d x wk(-1) for
      novice and intermediate training and 4-5 d x wk(-1) for advanced training.
      Similar program designs are recommended for hypertrophy training with respect to
      exercise selection and frequency. For loading, it is recommended that loads
      corresponding to 1-12 RM be used in periodized fashion, with emphasis on the 6-12
      RM zone using 1- to 2-min rest periods between sets at a moderate velocity.
      Higher volume, multiple-set programs are recommended for maximizing hypertrophy.
      Progression in power training entails two general loading strategies: 1) strength
      training, and 2) use of light loads (30-60% of 1 RM) performed at a fast
      contraction velocity with 2-3 min of rest between sets for multiple sets per
      exercise. It is also recommended that emphasis be placed on multiple-joint
      exercises, especially those involving the total body. For local muscular
      endurance training, it is recommended that light to moderate loads (40-60% of 1
      RM) be performed for high repetitions (> 15) using short rest periods (< 90 s).
      In the interpretation of this position stand, as with prior ones, the
      recommendations should be viewed in context of the individual's target goals,
      physical capacity, and training status.

PMID- 11828250
TI  - VO(2) slow component amplitude.

PMID- 11828252
TI  - Emerging concepts and technologies in melanoma research.
AB  - Melanoma research has made great advances in recent years. Particularly in the
      field of immunology, melanoma researchers have opened new avenues for basic and
      translational cancer research overall. Emerging research areas such as molecular
      epidemiology promise to develop a similar leadership role. On the other hand,
      research in biology, genetics or experimental therapy of melanoma has remained
      confined to few laboratories and entire research areas are not covered due to
      lack of researchers and resources. New developments in defining stem cells in
      skin and bone marrow enable us to develop new concepts for melanoma development
      and progression. New technologies allow rapid progress but they require close
      cooperation between laboratories. The field has to better bridge experimental
      with clinical research and increase communication. Corroboration with advocacy
      groups should activate the public for increased awareness and funding.

PMID- 11828253
TI  - Transient resistance to B16F10 melanoma growth and metastasis in CD43-/- mice.
AB  - CD43, the major transmembrane sialoglycoprotein of neutrophils, monocytes, T
      lymphocytes and platelets, is highly glycosylated and its high sialic acid
      content contributes to the strongly negative charge of cells. In this study the
      role of CD43 in melanoma development was addressed using CD43 -/- mice (null
      mutated for the corresponding gene or knockout [KO]). Growth of B16F10 melanoma
      was retarded in the KO mice compared with the wild-type CD43+/+ control (WT). A
      marked difference in lung colonization and other metastatic foci was observed in
      the KO and WT mice up to 15 days after intravenous injection of tumour cells. The
      initial resistance of KO mice was reversed with time, and in the long term there
      was no difference in the survival rate of the two animal groups. Transient
      resistance was attributed to increased adhesion of thrombin-activated platelets
      and leukocytes to melanoma and endothelial cells in KO mice. In the KO mice
      tumour emboli were found in the central portion of the lung more than at the lung
      periphery immediately after intravenous injection, in contrast to the WT mice.
      Activation of melanoma adhesion receptors by thrombin or TRAP stimulated lung
      colonization in WT but not KO mice. Therefore, the correlation of tumour embolism
      and metastasis in short-term experiments depends on the nature and stability of
      interactions between the tumour and the blood/endothelial cells of the host.

PMID- 11828254
TI  - L-2-Oxothiazolidine-4-carboxylate reverses the tumour growth-promoting effect of
      interleukin-2 and improves the anti-tumour efficacy of biochemotherapy in mice
      bearing B16 melanoma liver metastases.
AB  - The efficacy of sequential chemoimmunotherapy involving interleukin-2 (IL2) in
      metastatic melanoma is limited, in part, by the severe toxicity associated with
      most therapeutic regimens. Glutathione (GSH), the most prevalent intracellular
      non-protein thiol, plays an important role in protecting against cellular injury
      caused by various anticancer agents. GSH is also involved in the IL2-induced
      proliferative activity of immune system cells and some melanoma cells expressing
      IL2 receptors, such as B16 melanoma cells. The present study investigated the
      effect of selective manipulation of GSH using the cysteine prodrug l-2
      oxothiazolidine-4-carboxylate (OTZ) on the response of B16 melanoma to sequential
      biochemotherapy with cyclophosphamide (CY) and IL2. We found that OTZ, by
      depressing GSH levels, abrogates the in vitro growth-promoting effects of IL2 on
      B16 melanoma cells. The combination of OTZ plus IL2 in vivo also showed
      antitumour activity in mice bearing B16 melanoma liver metastases, significantly
      increasing their life span. Schedule dependency between both compounds was found;
      OTZ given intermittently in combination with daily IL2 administration was found
      to be the best therapeutic schedule. We also observed that whereas IL2 or OTZ
      alone added to CY resulted in a lower or non-significant improvement in the life
      span of the mice compared with tolerated doses of CY alone, the addition of both
      OTZ and IL2 to CY produced a significantly greater increase in survival than CY
      alone, and markedly protected mice against CY-induced toxicity, which allowed the
      administration of otherwise lethal doses of CY, with the CY activity/toxicity
      ratio being increased by four-fold.

PMID- 11828255
TI  - In vitro transformation of human congenital naevus to malignant melanoma.
AB  - The incidence of melanoma is estimated to be growing at the second fastest rate
      among all cancers in the United States. The progression of the melanocyte to a
      malignant melanoma involves various sequential steps: development of benign
      naevocellular naevus, preneoplastic dysplastic naevus, primary melanoma, and
      metastatic melanoma. Despite these clearly defined stages, very little is known
      about the molecular events leading to melanoma progression. We established a
      human congenital naevus cell line (UISO-CMN-1). UISO-CMN-1 cells were confirmed
      to have melanocytic origin by S100 immunoreactivity and the presence of melanin
      granules and melanosomes. UISO-CMN-1 cells, even though they showed structural
      and numerical abnormalities in karyotype, were non-tumorigenic when transplanted
      into athymic mice. However, following frequent exposure to ultraviolet C
      radiation, UISO-CMN-1 cells acquired tumorigenic potential. Transformation of
      UISO-CMN-1 cells into tumorigenic cells was accompanied by induction of
      ganglioside-2 expression without any significant changes in cellular ganglioside
      3. These transformed and non-transformed UISO-CMN-1 cell lines can serve as
      excellent research tools for studying the molecular changes associated with
      melanoma development and progression, and for identifying agents that might
      prevent development of malignant melanoma.

PMID- 11828257
TI  - Absence of mutations in the pleckstrin homology (PH) domain of protein kinase B
      (PKB/Akt) in malignant melanoma.
AB  - During recent years it has become evident that protein kinase B (PKB)/Akt plays
      an important role in oncogenic transformation. The gene for PKB/Akt has been
      found to be overexpressed in certain human tumours and a viral fusion protein
      gains transforming capacity. Recruitment to the plasma membrane is mandatory for
      the physiological activation of PKB/Akt; this shift from cytoplasm to the
      membrane is achieved by the N-terminal pleckstrin homology (PH) domain. We
      attempted to find out whether mutations of this domain were present in human
      malignant melanoma. RNA from 18 primary melanoma lesions of different sizes and
      histological subtypes and two melanoma metastases from 20 Caucasian patients were
      used for reverse transcription and subsequent polymerase chain reaction (PCR)
      amplification of the PH domain of PKB/Akt alpha. Cycle sequencing of the purified
      PCR products showed that mutations of the PH domain of PKB/Akt were absent in all
      20 melanoma specimens. In virtual Northern hybridizations PKB/Akt showed a low
      expression in both melanomas and acquired melanocytic naevi; however, no
      overexpression of PKB/Akt was detected. Thus in human melanoma PH domain
      mutations of PKB/Akt do not play a major role in melanoma carcinogenesis.

PMID- 11828256
TI  - Variability in glucose transporter-1 levels and hexokinase activity in human
      melanoma.
AB  - Melanoma exhibits heterogeneous growth patterns and widely varying sensitivities
      to multiple treatment modalities. This variability may reflect intrinsic genetic
      differences in factors giving rise to altered metabolism. Glucose is the primary
      energy source of tumours, including melanoma, and glucose transporter isoform 1
      (Glut-1) and hexokinase are key rate-limiting factors in glucose metabolism. The
      levels of Glut-1 and total hexokinase activity were measured in 31 melanoma
      biopsies to determine the extent of tumour-to-tumour variability in these
      parameters. Relative Glut-1 levels were determined by Western immunoblot analysis
      using human anti-Glut-1 rabbit polyclonal antibody, and hexokinase activity was
      measured in the same samples by an enzymatic assay monitoring the reduction in
      the oxidized form of nicotinamide adenine dinucleotide phosphate (NADP+) (in nmol
      NADP+ reduced/min per mg protein). All melanomas were from patients who had
      received no therapy prior to surgery. Immediately after excision, tumour biopsies
      were disaggregated to single cells by collagenase and DNase and frozen in liquid
      nitrogen. Thirty human melanomas exhibited a 22-fold variation in levels of Glut
      1 and 29 exhibited a nine-fold variation in total cellular hexokinase activity.
      Glut-1 levels and hexokinase activity were not correlated with one another. The
      broad range in Glut-1 levels and hexokinase activity observed between melanomas
      suggests that these glycolytic rate-limiting parameters that influence the rate
      of glucose metabolism may contribute to the variability in melanoma response to
      treatment modalities.

PMID- 11828258
TI  - Rarity of CDK4 germline mutations in familial melanoma.
AB  - To date, two genes have been implicated in melanoma pathogenesis. The first,
      CDKN2A, is a tumour suppressor gene with germline mutations detected in 20% of
      melanoma-prone families. The second, CDK4, is an oncogene with co-segregating
      germline mutations detected in only three kindreds worldwide. We examined 16
      American melanoma-prone families for mutations in all coding exons of CDK4 and
      screened additional members of two previously reported families with the Arg24Cys
      germline CDK4 mutation to evaluate the penetrance of the mutation. No new CDK4
      mutations were identified. In the two Arg24Cys families, the penetrance was
      estimated to be 63%. Overall, 12 out of 12 invasive melanoma patients, none out
      of one in situ melanoma patient, five out of 13 dysplastic naevi patients, two
      out of 15 unaffected family members, and none out of 10 spouses carried the
      Arg24Cys mutation. Dysplastic naevi did not strongly co-segregate with the
      Arg24Cys mutation. Thus the phenotype observed in melanoma-prone CDK4 families
      appears to be more complex than just the CDK4 mutation. Both genetic and
      environmental factors are likely to contribute to the occurrence of melanoma and
      dysplastic naevi in these families. In summary, although CDK4 is a melanoma
      susceptibility gene, it plays a minor role in hereditary melanoma.

PMID- 11828259
TI  - Differentially expressed genes identified in human melanoma cell lines with
      different metastatic behaviour using high density oligonucleotide arrays.
AB  - The increasing incidence of melanoma and the lack of effective treatment, with
      the exception of tumour excision before the onset of the metastatic phase, make
      it important to identify genes that may function as new molecular markers for
      diagnosis and/or prognosis or as new targets for therapy. Recently, a new
      technique using high density oligonucleotide arrays has been developed to
      simultaneously screen for the expression of thousands of genes. We used this
      technique to compare the mRNA expression patterns of two human melanoma cell
      lines with different metastatic behaviour. Eight differentially expressed genes,
      namely apolipoprotein CII, tyrosinase-related protein 1, transforming growth
      factor-beta superfamily, subtilisin-like protein, elongation factor 1 alpha2,
      alpha2-macroglobulin, human cell division cycle 10 and serine/threonine protein
      kinase (DYRK1A), were selected to validate the array results by Northern blotting
      and reverse transcription-polymerase chain reaction (RT-PCR). Furthermore, a
      reliable correlation between differential expression of these genes in the
      melanoma cell lines and in fresh lesions of melanocytic tumour progression was
      demonstrated by RT-PCR analysis. Altogether, our data indicate that high density
      oligonucleotide arrays are a valuable and reliable tool to screen for
      differentially expressed genes, and that our study may be considered a basic step
      in the characterization of genes that are involved in the (malignant) progression
      of melanoma.

PMID- 11828260
TI  - Tissue counter analysis of dermatoscopic images of melanocytic skin tumours:
      preliminary findings.
AB  - In tissue counter analysis, a novel image analysis tool in the evaluation of
      dermatoscopic images, a lattice of elementary measuring masks (elements) of equal
      size is randomly placed over the image and the contents of each element is
      evaluated by a set of colour and texture features. In this study, we tested the
      efficiency of tissue counter analysis on the diagnostic discrimination of benign
      and malignant melanocytic skin lesions. In order to assess the amount of benign
      and malignant tumour elements in each case, 20 cases each of naevus and malignant
      melanoma were sampled. Analysis was performed by the Classification and
      Regression Tree (CART), which provided a subclassification into 32 terminal nodes
      in the learning sets, 16 of them suggestive for the class 'malignant elements',
      the remaining 16 for 'benign elements'. For diagnostic assessment, only the
      percentage of the elements suggestive for malignancy in each lesion was used. ROC
      analysis showed that a threshold level of 36.45% classified all melanomas and 18
      out of 20 naevi correctly (sensitivity 100%, specificity 90%, positive predictive
      value 90.9%). Prospective studies with larger series of cases will have to be
      performed for clinical relevance.

PMID- 11828261
TI  - Histological, immunological and molecular features of a nasal mucosa primary
      melanoma associated with nasal melanosis.
AB  - Nasal mucosa melanoma is a rare entity that may occur together with nasal
      melanosis. The histological and immunological features and loss of heterozygosity
      analysis of such lesions have not been reported to date. In the study presented
      here short-term cell cultures were established from the patient's melanoma and
      subsequent relapses. Histology, immunohistochemistry, reverse transcription
      polymerase chain reaction enzyme-linked immunosorbent assay, human leukocyte
      antigen analysis, microdissection with subsequent polymerase chain reaction for
      analysis of loss of heterozygosity were used to characterize the tumour and other
      cells. Melanoma of the nasal cavity was found, with a surrounding proliferation
      of atypical melanocytes corresponding to nasal melanosis. Immunoreactivity was
      found for S-100, gp100, tyrosinase and MelanA protein. Loss of heterozygosity for
      a p16-flanking marker was found in the tumour and the melanotic cells. Short-term
      cell cultures expressed tyrosinase and MUC18 at the mRNA level and intercellular
      adhesion molecule-1 (ICAM-1) and interleukin-12 receptor at the protein level.
      This is the first time short-term cell cultures have been established and
      analysed from such a tumour. Melanoma-associated antigens were identified within
      the tumour. The melanoma and the melanotic cells showed loss of heterozygosity
      for the p16 gene, which is implicated in melanoma development. This points to a
      common origin in tumorigenesis. Pathways of tumour escape, such as expression of
      CD54 and interleukin-10, were observed. The clinical, immunological and molecular
      features suggest that nasal melanosis should be followed closely.

PMID- 11828262
TI  - Randomized, placebo-controlled trial of dietary supplementation of alpha
      tocopherol on mutagen sensitivity levels in melanoma patients: a pilot trial.
AB  - We evaluated the effects of vitamin E (dl-alpha-tocopherol) on mutagen
      sensitivity levels in a randomized placebo-controlled pilot trial. In brief, a
      dietary supplement of 1000 mg/day vitamin E or a placebo was randomly
      administered for 3 months to melanoma outpatients clinically free of the disease.
      Plasma vitamin E and mutagen sensitivity levels were measured at baseline and at
      the end of the trial after 3 months. At baseline, we found no significant
      differences in plasma vitamin E and mutagen sensitivity levels between the two
      groups. We also measured dietary intake at baseline and found dietary vitamin E
      to be a poor predictor of plasma levels of vitamin E. After 3 months of
      supplementation, we found that plasma levels of alpha-tocopherol increased
      significantly (P = 0.0005) in the vitamin E compared to the placebo group. We
      also found a non-significant, but consistent decrease in plasma gamma-tocopherol
      concentrations in the vitamin E supplemented compared to the placebo group. We
      did not find any significant difference between the vitamin E and placebo groups
      in mutagen sensitivity levels either at baseline or after 3 months of
      supplementation. We conclude that short term vitamin E supplementation, although
      it causes increased blood levels of alpha-tocopherol, does not provide protection
      against bleomycin-induced chromosome damage.

PMID- 11828263
TI  - Comparison of the efficacy of two different dosage dacarbazine-based regimens and
      two regimens without dacarbazine in metastatic melanoma: a single-centre
      randomized four-arm study.
AB  - The aim of this randomized four-arm phase III study was to evaluate whether there
      is a difference in activity between regimens containing dacarbazine and regimens
      without dacarbazine in metastatic melanoma, whether there is a dose-effect
      relationship for dacarbazine, and whether non-dacarbazine-containing aggressive
      regimens are in any way superior to non-aggressive ones. A total of 219 patients
      with metastatic cutaneous melanoma were included in this study; 196 of them were
      evaluable for activity. The patients were randomized into four treatment arms:
      arm A (standard dose dacarbazine arm), vincristine 1.4 mg/m2 on day 1, carmustine
      (BCNU) 60 mg/m2 on day 1, and dacarbazine 300 mg/m2 per 24 h on days 2-5; arm B
      (high-dose dacarbazine arm), vincristine and BCNU as in arm A and dacarbazine 600
      mg/m2 per 24 h on days 2-5; arm C ('aggressive' regimen without dacarbazine),
      vindesine 3 mg/m2 on day 1, bleomycin 7 mg/m2 per 24 h on days 1-4, and cisplatin
      30 mg/m2 per 24 h on days 5-8; arm D ('non-aggressive' regimen without
      dacarbazine), BCNU 100 mg/m2 on day 1 and procarbazine 90 mg/m2 per 24 h on days
      1-10. The four arms were well balanced with regard to patient- and disease
      related characteristics. On an intend-to-treat basis, the response rate was 11
      out of 49 (22%) in arm A, nine out of 47 (19%) in arm B, 16 out of 63 (25%) in
      arm C and nine out of 60 (15%) in arm D. There was a large overlap between the
      95% confidence intervals and no significant differences in the response rates
      between the four arms. Median survival in the four treatment arms was 4, 5, 6 and
      4 months, respectively, again with no significant differences. Median survival
      for responders (8, 11, 10 and 13 months, respectively) in all four arms was
      significantly longer than in non-responders (4, 3, 5 and 4 months, respectively).
      Arms A, B and C were significantly more toxic compared with arm D, which was for
      all practical purposes devoid of toxicities. The efficacy of all four regimens
      thus appeared comparable both in terms of response rate and survival. Responders
      in all four arms achieved a survival benefit. There does not seem to be a dose
      effect relationship for dacarbazine in metastatic melanoma. Chemotherapy from arm
      D, might be well suited for 'fragile' or elderly patients due to the lack of
      toxicity.

PMID- 11828264
TI  - Drugs for non-HIV viral infections.

PMID- 11828265
TI  - [Ultrasonographic and biochemical screening of adnexal masses before operative
      laparoscopy].
AB  - BACKGROUND: The object of our study was to evaluate how reliable ultrasonographic
      and biochemical screening of adnexal masses are in the selection of patients
      eligible for operative laparoscopy. METHODS: The study was performed at the First
      Clinic of Obstetrics and Gynecology, University of Rome La Sapienza, Italy.
      Eighty-seven women of 36.8 +/- 12 years of age, who underwent operative
      laparoscopy between January 1999 and January 2000 to remove an adnexal lesion,
      were enrolled. These adnexal lesions had been previously diagnosed on the basis
      of a pelvic ultrasonographic imaging; this was performed because of follow-up
      procedure or pelvic pain. The lesions were evaluated preoperatively according to
      Sassone echographic scoring system. The CA-125 level was determined in 58
      patients. RESULTS: Surgery was successful in all 87 cases. In one case the
      operative laparoscopy had to be turned into laparotomy since the histologic
      examination revealed an atypical proliferative mucinous cystoadenoma. Sassone
      total average echographic score was 6.0 +/- 1.7; this is below the discriminant
      cut-off for malignancy (9). The only case in which Sassone score reached 10 was
      an atypical cystoadenoma. The CA-125 level was higher than 35 IU/ml (cut-off of
      this marker) in 13.7% of the patients; these were all affected by endometriosis
      or had a hemorrhagic corpus luteum. In the patient with atypical cystoadenoma,
      the CA-125 level was within normal range (29.1 UI/ml). The post-operative period
      was uneventful in all cases but one, in which the occurrence of pulmonary
      thromboembolism required a prolonged hospitalization. CONCLUSIONS: The use of
      Sassone echographic scoring system proved to be very useful and effective in the
      selection of the patients. Tumor markers are relevant factors only if their
      evaluation is accompanied by an accurate anamnesis and is supported by the
      findings of abdominal and transvaginal ultrasonography.

PMID- 11828266
TI  - [Genetic mutations, acquired coagulation system disorders and obstetric
      pathology. Personal experience].
AB  - BACKGROUND: To evaluate the incidence of thrombophilic disorders such as Factor
      II mutation, Leiden factor V and MTHFR genotype, and anti-phospholipid anti
      bodies syndrome in women with or without pregnancy related problems. METHODS:
      Sixty-three patients (group A) with pregnancy complications were included in the
      study and tested for Factor V mutation, Factor II mutation, 5-10 MTHFR reductase
      mutation and anti-phospholipid antibodies syndrome. The incidence of disorders
      was compared with thirty-six pregnancies without complications (control study,
      group B). RESULTS: Hemostasis thrombophilic like disorders, were significantly
      high (p=0.001 vs group B). Nobody in both groups was homozygous for Leiden
      mutation or prothrombin mutation (Factor II). The prevalence of Factor V mutation
      in heterozygosis was significantly (p=0.01) higher in group A in comparison with
      group B. The MTHFR mutation in homozygosis was found in 21.4% of group A while in
      the control group it was 11%. Factor II mutation in heterozygosis and anti
      phospholipid antibodies were found only in group A. CONCLUSIONS: It is important
      to evaluate the hemocoagulation patterns in women with a history of complicated
      pregnancies.

PMID- 11828267
TI  - [Expression and prognostic significance in epithelial ovarian cancer].
AB  - BACKGROUND: Insulin-like growth factor binding protein-3 (IGFBP-3) is a
      glycoprotein with specific binding affinity to peptide hormones insulin-like
      growth factors (IGFs) which are potent mitogens for a variety of cells. IGFBP-3
      can inhibit the activities of IGFs by interfering with the interaction between
      IGFs and their receptor IGF-IR. Epithelial ovarian cancer (EOC) tissues express
      IGFBP-3, IGFs and IGF-IR. Moreover, high levels of IGF-I and IGF-IR have been
      shown in epithelial ovarian cancer, and IGF-I stimulates the growth of ovarian
      cancer. METHODS: We measured IGFBP-3 levels in ovarian cancer tissues of 147
      consecutive patients and we examined its association with clinical and
      pathological features of the disease and patient survival. The average age of the
      patients in the study was 55 years and the median follow-up time was 37 months.
      IGFBP-3 levels were measured in the tissue extracts by a commercial ELISA kit and
      non-parametric statistics and the Cox regression survival analysis were used to
      determine the associations of IGFBP-3 with clinical and pathologic variables as
      well as with patient survival. RESULTS: High IGFBP-3 levels resulted
      significantly associated with some of the favorable prognostic features of the
      disease, including early clinical stage (p=0.048), small size of residual tumor
      (p=0.007), and optimal debulking result (p=0.007). High IGFBP-3 was also
      associated with a significantly reduced risk for disease progression (RR=0.52,
      p=0.034) and we showed an inverse dose-dependent relationship between IGFBP-3 and
      disease progression-free survival (p=0.033). However, the association with
      disease progression-free survival was no longer statistically significant in a
      multivariate analysis. An association between IGFBP-3 and overall survival was
      not shown. CONCLUSIONS: This study suggest that IGFBP-3 may play a role in the
      progression of epithelial ovarian cancer.

PMID- 11828268
TI  - A new molecular and cytogenetic approach to sterility. A review of the
      literature.
AB  - In the therapeutic procedure of conjugal fertility, the use of intracytoplasmic
      sperm injection (ICSI) has opened new possibilities when conventional in vitro
      fertilization (IVF) techniques are unsuccessful. Cytogenetic studies showed the
      presence of genetic anomalies in foetuses conceived with this technique. Starting
      from these considerations, through a data collection of the literature, the
      authors report the latest scientific findings on this problem. They show the
      limits of the knowledge about genetic risks linked to these techniques,
      increasingly imposing rigorous medical behavior and conscious choices of the
      couple.

PMID- 11828269
TI  - [Growth factors in epithelial ovarian cancer].
AB  - The aim of this study was to provide an up-to-date review of the knowledge on the
      role of the main growth factors involved in the onset and progression of
      epithelial ovarian cancer (Transforming Growth Factor a-TGFa, Trans-forming
      Growth Factor-TGFb, Epidermal Growth Factor-EGF, Insulin-Like Growth Factor-IGF,
      Vascular Endothelial Growth Factor-VEGF). Relevant articles published between
      1991 and 2001 were identified using the Medline database. Publications identified
      by the search were reviewed and critically evaluated for their relevance to
      growth factors role in ovarian cancer. This review may be useful for clinicians
      wishing to study the biological mechanisms involved in epithelial ovarian
      neoplasms, in order to evaluate the possible value of Growth Factors as
      prognostic or predictive markers which could lead to novel therapeutic regimens,
      fitting individual needs based on single biological variations.

PMID- 11828270
TI  - [A natural alternative to menopausal hormone replacement therapy.
      Phytoestrogens].
AB  - Phytoestrogens are non-steroidal plant molecules whose structure differs from
      gonadal hormones, but with an estrogen-type bioactivity: they are capable of
      interacting with estrogen receptors, showing both agonist and antagonist methods
      of action. The beneficial effects of various classes of phytoestrogens present in
      nature are now known, but the main isoflavone present in soya, genistein, appears
      to be particularly effective. Interest in this substance is concentrated in
      particular on its therapeutic role in menopause. This paper is a review of the
      main studies published to date on the efficacy of phytoestrogens in reducing the
      symptoms of menopause. A diet rich in isoflavones is associated with a reduced
      incidence of vasomotor episodes; the average supplement of genistein is
      approximately 50 mg/day. After supplementing the diet with phytoestrogens,
      studies show a reduction in total cholesterol and LDL fraction. This is
      accompanied by an increase in BMD (Bone mineral density) after taking 90 mg of
      isoflavones for 6 months. Isoflavones may reduce the risk of developing breast
      cancer. The data examined confirm the excellent clinical efficacy of
      supplementing the diet with soy extracts, particularly genistein which is
      indicated to alleviate both the short-term symptoms of menopause and the long
      term effects, although the latter finding requires further subsantiation.

PMID- 11828271
TI  - Transvaginal color Doppler ultrasound for de novo ovarian carcinoma. How a good
      chance can be missed.
AB  - Early de novo ovarian cancer is one of the most challenging entities in
      gynecologic oncology as early diagnosis is extremely difficult. We describe the
      case of a 77-year woman who had incidental diagnosis of normally shaped ovaries
      with low resistance blood flow. Despite the suspicious finding and despite the
      documentation of elevated serum CA 125 levels she did not undergo surgery. Twelve
      months later she was found with an enlarged ovary. Laparotomy documented a stage
      IIIB ovarian carcinoma. Lack of communication among subspecialists and incomplete
      acceptance of new diagnostic aids contributed to this disappointing case.

PMID- 11828272
TI  - [Vena cava filter in patients with gynecologic cancer complicated by pulmonary
      embolism and progressive hypercoagulability].
AB  - The aim of the study was to verify the validity of placement of a vena cava
      filter in patients with gynecologic cancer complicated by pulmonary embolism and
      progressive persistent hypercoagulability. The authors discuss two patients with
      pulmonary embolism. In this study, a gynecologic tumor was diagnosed, one
      presented endometrial carcinoma and the other ovarian papillary carcinoma, after
      the position of vena cava filter and treatment with urokinasi (2.800.000 UI/ml)
      it was possible to do surgery followed by radiation therapy in the first case and
      chemotherapy in the second. In these cases there are indications for the
      placement of a vena cava filter. This has enabled surgery and anticoagulation
      therapy and has prevented the movement of any other emboli, which were later
      dissolved by fibrinolytic agents, and the effectiveness result was the arrest of
      progressive hypercoagulability moved by tumor cell. The serious conditions that
      were related to prior embolism and to a persistent thrombotic state characterized
      by progressive hypercoagulability did not make it possible to perform surgery or
      any other type of therapy because of absolute contraindications. The decision to
      place the filter could thus become the first step towards subsequent
      improvements, that are also tied to the possibility of performing surgery for
      removing tumor, arrest of progressive hypercoagulability due to tumor cell, allow
      chemotherapy or radiation treatment.

PMID- 11828274
TI  - [A new organizational model of hospitals and law].
AB  - One of the more important legislative news in Italy is the company management of
      the National Health Care. The Health Care System has a long time budget and a
      yearly time budget, which allow to achieve some objectives identified inside an
      organizing system, based on Departments and their Directors. Another point is the
      competitivity among public/public and public/private structures. The problem of
      the penal responsibility of the medical doctor and staff is discussed.

PMID- 11828273
TI  - [Clinical effects of hormone replacement therapy with estradiol valerate and
      cyproterone acetate in perimenopausal women].
AB  - BACKGROUND: In perimenopause many women complain of psychogenic and organic
      disorders often connected with initial and increasing levels of hypoestrogenism.
      In this study we evaluated the effects of hormone replacement therapy (HRT) in
      symptomatic women in perimenopause. METHODS: We enrolled 100 healthy and
      symptomatic women who were randomly distributed to two groups for a 12-month
      study. Group A: 50 patients received HRT with estradiol valerate and cyproterone
      acetate (Pausene(R)); Group B: 50 patients were used as a control group (treated
      with Cacit Vitamin D30(R)). A number of clinical and instrumental tests were
      performed at 0, 6 and 12 months to evaluate any changes in vasomotor and
      urogenital symptoms, bone and serum homeostasis and possible sexual disorders.
      The statistical analysis was performed using the c2 test. RESULTS: The group of
      women receiving HRT showed a significant reduction in vasomotor clinical symptoms
      (p<0.001) and sexual disorders (p<0.002); this was not reflected in the control
      group where libido decreased steadily with apparent slight improvements only at
      the end of the study. The urogenital disorders disappeared almost completely in
      Group A, whereas they diminished in Group B. HRT patients also showed a slight
      increase (p<0.001) in the initial value of BMD (bone mineral density), a
      reduction in the marker for bone turnover and an improved lipid profile (p<0.05).
      These changes were unfortunately not noted in Group B. CONCLUSIONS: On the basis
      of these results we conclude that HRT appeared to have a beneficial effect on
      perimenopausal clinical symptoms over the 12-month period, leading to marked
      improvements in the psychophysical wellbeing of symptomatic women in
      perimenopause.

PMID- 11828275
TI  - [Spontaneous delivery or cesarean section: incentives to mothers].

PMID- 11828276
TI  - What operation for acute type A dissection?

PMID- 11828277
TI  - A prospective randomized trial of endoscopic versus conventional harvesting of
      the saphenous vein in coronary artery bypass surgery.
AB  - OBJECTIVES: Our objectives were (1) to determine whether minimally invasive
      endoscopic harvesting of the saphenous vein reduces morbidity due to
      postoperative wound infection and pain with improved cosmetic results and
      mobilization as compared with the conventional technique and (2) to compare the
      histologic properties of the saphenous veins harvested conventionally and
      endoscopically. METHODS: One hundred forty-four patients undergoing coronary
      artery bypass grafting were randomized to have vein harvesting performed by
      either the conventional (n = 72) or an endoscopic (n = 72) minimally invasive
      technique. RESULTS: Vein harvest time (open leg wound time) was significantly
      reduced in the endoscopic group (27.6 vs 64.4 minutes; P <.0001). The rate of leg
      wound infection was significantly reduced in the endoscopic group (4.3%) as
      compared with the conventional group (24.6%), a relative risk reduction of 83%
      (95% confidence interval: 36%-129%; P =.0006). The majority of infections (84.2%)
      occurred after hospital discharge. Postoperative leg pain, mobilization, and
      overall patient satisfaction were also significantly improved in the endoscopic
      group. Double blinded histologic assessment of harvested vein (n = 28) showed no
      evidence of any clinically important significant damage to the specimens in
      either group. CONCLUSIONS: In this prospective randomized trial, endoscopic
      harvesting of the saphenous vein significantly reduced postoperative leg wound
      complications, including infection, and improved patient satisfaction as compared
      with the conventional harvesting technique. There were no significant histologic
      differences between the conventional and endoscopically harvested saphenous
      veins.

PMID- 11828278
TI  - Antithrombin III concentrate to treat heparin resistance in patients undergoing
      cardiac surgery.
AB  - OBJECTIVE: The purpose of this report is to describe the clinical use of
      antithrombin III concentrate in 53 patients who were found, in the operating room
      before cardiopulmonary bypass, to be heparin resistant. METHOD: Resistance to
      heparin was determined to be present when greater than 600 U/kg body weight of
      heparin failed to prolong the kaolin-activated clotting time to more than 600
      seconds in 53 aprotinin-treated patients. Blood samples were obtained for
      subsequent antithrombin III activity determination. Patients were then
      administered 500 U of antithrombin III concentrate, and the activated clotting
      time was remeasured. If the activated clotting time remained less than 600
      seconds, a second 500-U dose was given. RESULTS: Of the 53 patients, 45 (85%) had
      subnormal measured antithrombin III activity, and the mean plasma antithrombin
      III activity level for the entire group was 67% (normal 80%-120%). Administration
      of antithrombin III concentrate (500 U in 45 patients and 1000 U in 8 patients)
      resulted in prolongation of the mean activated clotting time from 492 to 789
      seconds without additional heparin. The mean heparin dose response increased from
      36.5 to 69.3 s x U(-1) x mL(-1) with antithrombin III treatment. Only one patient
      did not achieve the target activated clotting time, despite administration of
      greater than 600 U/kg heparin and 1000 U of antithrombin III concentrate, and was
      treated with fresh-frozen plasma. CONCLUSIONS: On the basis of the criterion used
      in this report, most of the patients defined as being heparin resistant had
      subnormal plasma antithrombin III activity. Treatment with antithrombin III
      concentrate resulted in potentiation of the heparin effect to meet predetermined
      activated clotting time thresholds and allow for cardiopulmonary bypass.

PMID- 11828279
TI  - Leukocyte depletion attenuates expression of neutrophil adhesion molecules during
      cardiopulmonary bypass in human beings.
AB  - BACKGROUND: On the basis of scanty information, the effects of a leukocyte filter
      during cardiac operations in human beings have been examined from the viewpoint
      of the expression of neutrophil adhesion molecules. This study was therefore
      designed to determine whether leukocyte depletion during cardiopulmonary bypass
      may interfere with neutrophil adhesion properties. METHODS: Twenty-four patients
      undergoing elective heart operations were randomly allocated to a leukocyte
      depletion group or a control group. Blood samples were collected at 7 points:
      before sternotomy, at 10, 30, and 60 minutes of cardiopulmonary bypass, at
      termination of cardiopulmonary bypass, 5 minutes after protamine administration,
      and 2 hours after cardiopulmonary bypass. The expression of the neutrophil
      surface adhesion molecules L-selectin and beta2-integrins was determined by flow
      cytometric analysis in whole blood. RESULTS: (1) CD11a expression did not change
      significantly in either group. There were no significant differences between
      control and leukocyte-depletion groups (P =.63). (2) There was a significantly
      higher expression of CD11b on the neutrophils during cardiopulmonary bypass in
      the control group than in the leukocyte-depletion group (P =.01). (3) CD11c
      expression was initially up-regulated from the onset of cardiopulmonary bypass,
      reaching a peak at 60 minutes after bypass in the control group (P =.02). The
      expression of CD11c did not differ significantly between groups (P =.23). (4) L
      selectin expression was significantly lower in the leukocyte-depletion group than
      in the control group (P =.03). CONCLUSIONS: The major findings of the present
      study in human subjects undergoing elective cardiac operations with
      cardiopulmonary bypass are as follows: (1) bypass was associated with an up
      regulation of the adhesion molecules L-selectin, CD11b, and CD11c but with no
      significant change in CD11a expression, and (2) the clinical use of a leukocyte
      depleting filter could down-regulate the expression of CD11b and L-selectin.

PMID- 11828280
TI  - Revascularization of the lateral wall: long-term angiographic and clinical
      results of radial artery versus right internal thoracic artery grafting.
AB  - OBJECTIVE: We sought to evaluate whether the radial artery provides the same
      results as the right internal thoracic artery in lateral wall revascularization
      in the long term. METHODS: From January 1992 to September 1996, 288 patients had
      myocardial revascularization with the left internal thoracic artery anastomosed
      to the left anterior descending coronary artery. The lateral wall was grafted
      with the radial artery in 139 patients (group A) and with the right internal
      thoracic artery in 149 patients (group B). Groups were different only because of
      older age and a higher incidence of patients requiring urgent treatment in group
      A. Y grafting was used in 86.4% of patients in group A and in 34.8% of patients
      in group B (P < .001). Anastomoses per patient were similar in both groups (3.2
      +/- 0.8 vs 3.2 +/- 0.9, P = 1.000). RESULTS: Thirty-day mortality was similar
      (2.1% vs 2.0%, P = .722). There were 15 late deaths in group A versus 11 in group
      B (P = .418). Cause of death was cardiac related in 6 patients in group A versus
      7 in group B. Late redo or percutaneous transluminal coronary angioplasty was
      performed in 3 patients in group A and in 1 patient in group B (P = 0.538). Eight
      year survival was 86.7% +/- 2.9% in group A versus 89.6% +/- 2.8% in group B (P =
      .477); event-free survival was 84.2% +/- 3.2% versus 88.9% +/- 2.9%, respectively
      (P = .430). The patency rate within 30 days was 99.1% in group A (105/106 left
      internal thoracic artery plus radial artery anastomoses) versus 100% in group B
      (52/52 bilateral internal thoracic artery anastomoses; P = .715). After a mean of
      35 +/- 28 months, the patency rate was 99.0% in group A (100/101 left internal
      thoracic artery plus radial artery anastomoses) and 100% in group B (33/33
      bilateral internal thoracic artery anastomoses, P = .560). CONCLUSION: In the
      long-term, lateral wall grafting with the radial artery provides the same
      clinical and angiographic results as right internal thoracic artery grafting.

PMID- 11828281
TI  - Benefits of prophylactic continuous infusion of furosemide after the maze
      procedure for atrial fibrillation.
AB  - OBJECTIVES: One of the most significant complications seen after the maze
      procedure for atrial fibrillation is excessive fluid retention, with subsequent
      pulmonary complications. To address this problem we recently started treating all
      patients prophylactically with a continuous infusion of furosemide starting
      immediately after the operation. METHODS: Seventy-five consecutive patients with
      statistically similar demographic characteristics were divided into two groups.
      In the continuous infusion group (n = 36) furosemide was given intravenously as a
      continuous infusion at a dose of 2 to 15 mg/h for the first 48 hours after the
      operation, and in the bolus dose group (n = 39) furosemide was administered in
      bolus doses (50-100 mg) to maintain a targeted daily urinary output of 25 to 50
      mL/kg. Hemodynamic data, urinary output, fluid balance, daily weights, and
      pulmonary complications were recorded during the first 48 hours after the
      operation. RESULTS: The mean postoperative urinary output was higher, the total
      furosemide dose was lower, and the pulmonary complications were fewer in the
      continuous infusion group than in the bolus dose group. Three patients in the
      bolus dose group were reintubated after the operation, whereas none in the
      continuous infusion group were reintubated. Supplemental oxygen requirements were
      greater in the bolus dose group (7 vs 4 patients, P <.05). In the bolus dose
      group, 4 patients (10%) required thoracentesis and 3 patients (8%) required chest
      tube insertions for postoperative pleural effusions, in contrast with 1 patient
      (3%) each in the continuous infusion group (P <.05). CONCLUSION: Despite a
      smaller total dose relative to bolus infusion, prophylactic continuous furosemide
      infusion decreased the adverse pulmonary complications associated with excessive
      fluid retention in patients undergoing the maze procedure for atrial
      fibrillation.

PMID- 11828282
TI  - Predictors of outcome after the Fontan operation: is hypoplastic left heart
      syndrome still a risk factor?
AB  - OBJECTIVE: This study was undertaken to evaluate factors contributing to a
      decrease in early mortality and morbidity after the Fontan procedure between
      January 1, 1992, and December 31, 1999. METHODS: Outcomes evaluated were early
      survival, duration of pleural effusions, and duration of hospitalization.
      Potential predictors evaluated included anatomic diagnosis, presence of a common
      atrioventricular valve, preoperative pulmonary artery pressure, type of Fontan
      operation, type of intentional right-to-left shunt or baffle fenestration, and
      use of modified ultrafiltration. RESULTS: The modified Fontan procedure was
      performed in 332 patients at a median age of 22 months (range, 11-380 months) and
      a median weight of 11 kg (range, 5.8-120 kg). Prior stage I reconstructive
      surgery for classic or variant hypoplastic left heart syndrome had been performed
      in 205 (53%) of 332 patients, and 318 (96%) had undergone an interim superior
      cavopulmonary connection. A lateral-tunnel Fontan operation was performed in 281
      patients, and an extracardiac conduit Fontan operation was performed in 51
      patients. An intentional right-to-left shunt was created in 298 (90%) patients.
      Between 1992 and 1999, the outcome after the modified Fontan operation improved
      significantly. Overall mortality was 6.6% (22/332), with only 2 deaths since
      1994. Morbidity was also reduced, with a decreased duration of pleural effusions
      and decreased hospital stay. In a multivariable analysis of the entire cohort,
      only the presence of a common atrioventricular valve (odds ratio, 7.64; 95%
      confidence limits, 2.07-28.14; P =.0002) and increased preoperative pulmonary
      artery pressure (odds ratio, 1.46/1 mm Hg increase; 95% confidence limits, 1.2
      1.78; P <.001) increased the risk of early death, whereas use of a single-punch
      fenestration in a lateral-tunnel Fontan (odds ratio, 0.06; 95% confidence limits,
      0.01-0.65; P =.02) and use of modified ultrafiltration (odds ratio, 0.14; 95%
      confidence limits, 0.03-0.72; P =.019) decreased the risk of death. The risk of
      prolonged pleural effusions (>3 days) was increased in patients with hypoplastic
      left heart syndrome (odds ratio, 1.73; 95% confidence limits, 1.07-2.81; P =.03)
      and was decreased by use of a single-punch fenestration in a lateral-tunnel
      Fontan operation (odds ratio, 0.17; 95% confidence limits, 0.07-0.4; P <.001), as
      well as by the use of modified ultrafiltration (odds ratio, 0.25; 95% confidence
      limits, 0.15-0.40; P <.01). CONCLUSIONS: In a contemporary series of Fontan
      operations performed largely in patients with hypoplastic left heart syndrome or
      variants, systemic ventricle morphology had no effect on mortality. Some patient
      characteristics, however, continue to influence outcome. The decrease in
      mortality and morbidity in the current era is attributed to changes in management
      strategies, specifically the use of modified ultrafiltration and baffle
      fenestration.

PMID- 11828283
TI  - Outcome after reconstruction of discontinuous pulmonary arteries.
AB  - OBJECTIVE: This study was undertaken to determine outcomes of and optimal
      treatment strategies for reconstruction of congenital or acquired discontinuity
      of branch pulmonary arteries. METHODS: Between 1985 and 2000 pulmonary artery
      continuity was established in 102 patients with discontinuous central pulmonary
      arteries and normal peripheral arborization. Data were obtained retrospectively.
      RESULTS: Techniques to connect both pulmonary arteries included direct pulmonary
      artery-pulmonary artery anastomosis (n = 33), tube graft interposition (n = 47),
      or pulmonary arterial implantation in right ventricular-pulmonary arterial
      conduits (n = 22). Among patients with biventricular repair (n = 66), survival
      was 85% +/- 8% at 5 years, and freedom from surgical or interventional pulmonary
      arterioplasty was 31% +/- 11%. At most recent follow-up, mean branch pulmonary
      arterial z scores were -0.5 +/- 1.6 (right pulmonary artery) and -1.4 +/- 1.3
      (left pulmonary artery). Mean right to left ventricular pressure ratio was 0.61
      +/- 0.26, and this value was more than 0.75 in 13 of 58 cases. Fifteen of 51 had
      a lung perfusion mismatch of more than 75:25, and in 9 of 58 one branch pulmonary
      artery was occluded. Twenty-two patients who underwent primary establishment of
      antegrade pulmonary artery flow without previous shunt procedures had comparable
      survival and reintervention rates, with a tendency toward higher pulmonary
      arterial z scores and lower right to left ventricular pressure ratios. Among
      patients with single-ventricle repair (n = 33), 5-year survival was 93% +/- 8%
      and freedom from pulmonary arterioplasty was 39% +/- 9%. Ten of 19 patients had a
      lung perfusion mismatch, and one branch pulmonary artery was occluded in 4 of 31.
      Overall, a direct pulmonary artery anastomosis was associated with better
      survival (P =.006). The presence of aortopulmonary collaterals was a risk factor
      for pulmonary artery occlusion (P =.03). CONCLUSION: Good survival can be
      achieved for patients with pulmonary artery discontinuity, but this requires
      frequent reinterventions. Direct pulmonary artery- pulmonary artery anastomoses
      and control of all collateral vessels may further improve outcome.

PMID- 11828284
TI  - Procedural factors associated with early postoperative arrhythmias after repair
      of congenital heart defects.
AB  - OBJECTIVES: Early postoperative arrhythmias frequently are a relevant problem in
      the early postoperative management after surgical intervention for congenital
      heart disease. Few data are available indicating risk factors for their
      occurrence. The hypothesis was tested that factors closely related to the
      surgical procedure itself were associated with a higher incidence of arrhythmias
      early in the postoperative course after repair of congenital heart disease.
      METHODS: All consecutive patients undergoing 1 of 3 well-defined surgical
      procedures were prospectively evaluated for the occurrence of arrhythmias during
      the entire postoperative hospital stay by means of continuous
      electrocardiographic monitoring in the intensive care unit and use of 24-hour
      Holter monitors. Patients examined were those undergoing transatrial closure of a
      ventricular septal defect, repair of complete atrioventricular canal, and
      tetralogy of Fallot. The relation between procedural variables and the occurrence
      of arrhythmias was independently evaluated for each of these 3 heart defects.
      RESULTS: Early postoperative arrhythmias occurred in 30% of patients with
      ventricular septal defect (n = 75), 35% of patients with tetralogy of Fallot (n =
      52), and 47% of patients with atrioventricular canal (n = 45). Patients with
      arrhythmias tended to be younger (significant only in the ventricular septal
      defect group). In all 3 patient groups, there was a significant correlation
      between incidence of arrhythmias and longer extracorporeal bypass time (P <.05)
      and longer aortic crossclamp time (P <.01), as well as with higher maximum
      postoperative troponin serum levels (P <.01). In patients with atrioventricular
      canal, there was a significant relation between hemodynamically incomplete
      surgical results and the occurrence of arrhythmias (P <.01). CONCLUSIONS: The
      occurrence of early postoperative arrhythmias after repair of congenital heart
      disease was significantly associated with procedure-related risk factors in each
      of 3 independent patient groups undergoing well-defined surgical procedures.

PMID- 11828285
TI  - Histomorphometric analysis of pulmonary vessels in single ventricle for better
      selection of patients for the Fontan operation.
AB  - OBJECTIVE: In cases of single-ventricle physiology, the Fontan procedure often
      fails even when the usual selection criteria are strictly respected. We analyzed
      specimens from intraoperative open lung biopsies performed on 40 patients with
      single-ventricle physiology who were considered to be good candidates for the
      Fontan procedure. Histomorphometric study was performed to determine histologic
      factors predictive of failure of the Fontan procedure. METHODS: Histomorphometric
      studies were performed on samples from 40 patients aged 6 months to 23 years with
      single-ventricle physiology, either tricuspid atresia (n = 14) or univentricular
      heart (n = 26). The preoperative pulmonary arterial pressure was 18 mm Hg or less
      in 35 cases and greater than 18 mm Hg in 5 cases. Eighteen patients underwent
      total cavopulmonary connection, 16 patients underwent partial cavopulmonary
      connection, and 6 underwent a palliative procedure, as determined according to
      clinical and hemodynamic findings. RESULTS: Lung biopsy specimens from all 5
      patients with pulmonary arterial pressure greater than 18 mm Hg appeared
      abnormal, whereas they appeared abnormal only 51% of the time in the low
      pulmonary arterial pressure group. The most frequent histologic abnormality
      observed was extension of smooth muscle cells in the wall of distal intra-acinar
      pulmonary arteries. Of the 18 patients who underwent the Fontan procedure, 9 had
      normal distal pulmonary arteries and good surgical results (except 1 with the
      Fontan circulation taken down for an anatomic reason). The remaining 9 had thick
      walled distal intra-acinar pulmonary arteries with poor results of the Fontan
      procedure, and 6 died. The mean percentage wall thickness of small intra-acinar
      pulmonary arteries was significantly greater among the patients with bad results
      than among those with good results of the procedure (P <.01). CONCLUSIONS: Lung
      biopsy specimens were abnormal in 51% of patients with low pulmonary arterial
      pressure, there was no relationship between preoperative pulmonary arterial
      pressure and outcome, and extension of muscle in peripheral arteries was always
      present in cases of failure of the Fontan procedure. Histomorphometric study is
      therefore a useful adjunct to the usual selection criteria for surgical decision
      making in cases of single-ventricle physiology.

PMID- 11828286
TI  - Radical en bloc resection for lung cancer invading the spine.
AB  - OBJECTIVE: We reviewed our 8-year experience with en bloc partial and total
      vertebrectomy for lung cancer invading the spine and report outcome and survival.
      METHODS: Nineteen patients with lung cancers involving the spine underwent en
      bloc resection. Eleven received induction treatment (chemotherapy, n = 5;
      chemoradiotherapy, n = 4; and radiation, n = 2). Pneumonectomy was performed in 3
      patients, lobectomy in 13 patients, and wedge resection in 3 patients.
      Hemivertebrectomy was performed in 15 patients, and total vertebrectomy was
      performed in 4 patients. The median number of resected vertebral bodies was 3
      (range, 1-4). Tumor stage was IIIB in 14 patients, IIIA in 1 patient, and IIB in
      4 patients (hemivertebrectomy is performed in the case of T3 disease to obtain
      free margins). Surgical nodal status was N0 in 13 patients, N1 in 3 patients, N2
      in 1 patient, and N3 (supraclavicular) in 2 patients. Complete macroscopic and
      microscopic resection was achieved in 15 (79%) patients. RESULTS: There was no
      immediate postoperative mortality. Morbidity was observed in 10 patients,
      including 4 (21%) complications related to the spinal surgery. The median
      hospital stay was 30 days. Seven patients were alive after a mean follow-up of 26
      months (range, 7-74 months). The 1- and 5-year predicted survivals (updated) are
      59% and 14%, respectively. Nine local recurrences were observed. CONCLUSIONS: En
      bloc resection of chest tumors with vertebrectomy is technically demanding, and
      postoperative morbidity should be critically addressed with this aggressive
      surgical intervention. However, an encouraging long-term survival observed in
      this series suggests that en bloc resection could be a valid option in selected
      patients with vertebral involvement of chest tumors.

PMID- 11828287
TI  - Impact of comorbidity on survival after surgical resection in patients with stage
      I non-small cell lung cancer.
AB  - OBJECTIVE: As the mean age in patients with non-small cell lung cancer increases,
      the proportion of patients with serious comorbidity who are considered for
      surgical resection also increases. Patients with non-small cell lung cancer have
      been shown to have a higher burden of comorbidity than do patients with tumors of
      other sites, such as breast, prostate, colon, and head and neck. The goal of this
      review was to determine the impact of comorbidity on postoperative and long-term
      survival after surgical resection in patients with stage I non-small cell lung
      cancer. METHODS: A database analysis of our hospital's tumor registry included
      451 patients who underwent surgical resection for pathologic stage I non-small
      cell lung cancer between January 1, 1994, and December 31, 1999. Comorbidity
      severity was prospectively determined with the Kaplan-Feinstein Index. Survival
      data were collected for each patient from the date of operation, with a mean
      duration of follow-up of 35.7 months. Bivariate statistics and Cox proportional
      hazards model analyses were used. RESULTS: The mean age was 64.4 years, and 249
      (55%) patients were male. The distribution of overall comorbidity severity was
      none, 142 (31.5%); mild, 150 (33.3%); moderate, 115 (25.5%); and severe, 44
      (9.8%). The overall in-hospital mortality was 2.2% (n = 10/451). There was a
      nonsignificant trend toward higher hospital mortality with greater comorbidity:
      none, 0.7% (n = 1/142); mild, 3.3% (n = 5/150); moderate, 0.9% (n = 1/115); and
      severe, 6.8% (n = 3/44, P =.055). Kaplan-Meier estimated survivals at 3 years for
      each level of comorbidity were as follows: none, 85.6%; mild, 74.8%; moderate,
      68.8%; and severe, 70.0% (P <.002). After adjustment for age, sex, T status, and
      tumor histologic type, the relative risks of death as a function of comorbidity
      were mild, 1.44 (95% confidence interval 0.89-2.34); moderate, 2.28 (95%
      confidence interval 1.43-3.65); and severe; 1.94 (95% confidence interval 1.023
      3.70). CONCLUSIONS: Comorbidity has a significant impact on survival after
      surgical resection of patients with stage I non-small cell lung cancer. These
      data may help to explain the lower than expected survival results for patients
      after surgical resection for stage I non-small cell lung cancer.

PMID- 11828288
TI  - Contrasting natures of lung growth after transplantation and lobectomy.
AB  - OBJECTIVE: We hypothesized that posttransplantation lung growth in an immature
      recipient and postlobectomy compensatory lung growth are two distinct processes.
      METHODS: Mature swine underwent left upper lobectomy, and growth of the left
      lower lobe was studied after 2 weeks and after 3 months. Left lower lobes from
      another set of mature pigs were transplanted into immature animals, and growth of
      the transplanted lobe was then studied after 2 weeks and after 3 months. Left
      lower lobes from mature animals that did not undergo operation were used as
      normal control lobes. The lobes were weighed on removal and fixed
      intrabronchially. Sections stained with hematoxylin and eosin were used to
      determine alveolar surface density and percentage volume of respiratory region.
      Immunostaining for 5-bromo-2'-deoxyuridine was used to determine alveolar cell
      proliferation index, and epidermal growth factor receptor expression was detected
      by Western blot. RESULTS: Postlobectomy lung growth (increase in lobe weight)
      reached statistical significance at 2 weeks, with a concomitant rise in cell
      proliferation index. The transplanted lobe, in contrast, exhibited a gradual
      growth response, with a statistically significant increase in cell proliferation
      index at 3 months. Volume of respiratory region was noted to increase only in the
      transplanted lobe at 3 months. Epidermal growth factor receptor expression was
      upwardly regulated relative to that in normal control lobes in the 2-week
      postlobectomy and 3-month posttransplantation lobes. CONCLUSIONS: Postlobectomy
      lung growth appears to be regulated by a different mechanism than is
      posttransplantation lung growth and is a more rapid and restorative process. The
      growth peaks in both processes correlate with upward regulation of cell
      proliferation index and epidermal growth factor receptor expression.

PMID- 11828289
TI  - Induction of apoptosis in malignant pleural mesothelioma cells by activation of
      the Fas (Apo-1/CD95) death-signal pathway.
AB  - OBJECTIVE: Although well characterized in several solid tumors, the effects of
      Fas/Fas ligand interactions in malignant pleural mesothelioma cells have not been
      defined. The present study was undertaken to examine the functional status of the
      Fas/Fas ligand pathway in malignant pleural mesothelioma cells and to determine
      the feasibility of targeting this death-signal pathway for molecular intervention
      in patients with mesotheliomas. METHODS: Fas expression in primary normal human
      bronchial epithelial cells and 6 malignant pleural mesothelioma cell lines was
      quantified by means of flow cytometry. The caspase components of the Fas-mediated
      apoptotic pathway were evaluated by means of Western blot techniques. Soluble Fas
      ligand-mediated cytotoxicity and apoptosis were evaluated by means of MTS and
      TUNEL assays, respectively. Cisplatin (3 microg/mL) and lymphokine-activated
      killer cells were used to enhance mesothelioma sensitivity to soluble Fas ligand.
      An H2373 nude mouse xenograft model of malignant pleural mesothelioma was
      established to assess the in vivo effects of soluble Fas ligand. RESULTS: Four of
      6 malignant pleural mesothelioma lines exhibited high levels of Fas expression,
      and 2 of 4 were inherently susceptible to soluble Fas ligand-mediated
      cytotoxicity (soluble Fas ligand 50% inhibitory concentration, < 15 ng/mL). Two
      soluble Fas ligand refractory cell lines (H2052 and H513) exhibited high levels
      of Fas receptor. Pretreatment with cisplatin resulted in a reduction of 50%
      inhibitory concentration from infinity to 4.17 +/- 0.14 ng/mL and 10.23 +/- 1.58
      ng/mL, respectively. Two additional soluble Fas ligand refractory cell lines
      (H2595 and REN) expressed low levels of Fas. Exposure of these cells to
      lymphokine-activated killer cells or lymphokine-activated killer cell-conditioned
      medium followed by a 24-hour treatment with cisplatin resulted in a significant
      reduction in 50% inhibitory concentration of soluble Fas ligand and pronounced
      induction of apoptosis. Intraperitoneally administered soluble Fas ligand
      mediated regression of H2373 xenografts. CONCLUSION: The Fas/Fas ligand pathway
      in mesothelioma cells is either intrinsically intact or can be rendered
      functional with chemotherapeutic agents or immune effector cells. These
      preclinical data support further evaluation of strategies to enhance Fas-mediated
      apoptosis in mesotheliomas.

PMID- 11828290
TI  - Bronchial carcinoid tumors: surgical management and long-term outcome.
AB  - OBJECTIVE: We sought to determine the variables influencing long-term survival of
      patients treated for bronchial carcinoid tumors. METHODS: A retrospective, mono
      institutional review of patients subjected to surgical treatment since 1977 was
      conducted. RESULTS: Over 22 years, 126 patients with a final histologic diagnosis
      of bronchial carcinoid tumors were assessed for surgery. The group comprised 72
      men (57%) and 54 women (43%) with a mean age at presentation of 47 +/- 16 years
      (range 11-77 years). Symptoms were present in 65 (53%) patients. Operations
      included lobectomy or bilobectomy in 88 (with 4 bronchoplastic procedures),
      pneumonectomy in 15, segmentectomy in 3, wedge resection in 16, and bronchial
      sleeve resection in 3 patients. One patient (0.7%) died in the perioperative
      period. Eighty-two patients (65%) had typical and 44 (35%) had atypical carcinoid
      tumors. Postoperative staging was complete for 113 of 126 patients (13 patients
      did not undergo lymphadenectomy): 90 patients had stage I disease, 6 had stage
      II, 15 had stage III, and 2 had stage IV disease. A typical subtype was stage I
      in 70 and more advanced (II-IV) in 5, whereas an atypical subtype was stage I in
      20 and more advanced in 18 (P <.05). Mean follow-up was 99 +/- 73 months (range 6
      282 months) during which 19 (15%) patients died (12 of recurrent disease).
      Recurrent tumor developed in 4 (5.5%) of 72 patients affected by typical subtypes
      and 8 (19.5%) of 41 by atypical subtypes with complete follow-up. Overall
      survival at 15 years was 74%; survival related to histologic type and nodal
      status at 15 years was significant (P <.05). CONCLUSIONS: Biologic behavior and
      prognosis for bronchial carcinoid tumors are better than for other lung cancers.
      Surgical treatment requires radical excision and lymph node sampling. Survival
      and long-term outcome are significantly related to the histologic type, nodal
      status, and pathologic stage.

PMID- 11828291
TI  - Inhibition of nuclear factor kappaB chemosensitizes non-small cell lung cancer
      through cytochrome c release and caspase activation.
AB  - OBJECTIVE: Although we have previously shown that inhibition of nuclear factor
      kappaB sensitizes non-small cell lung cancer cells to chemotherapy-mediated cell
      death, the apoptotic pathways mediating this process are unknown. The purpose of
      this study was to determine whether chemosensitivity after the inhibition of
      nuclear factor kappaB in non-small cell lung cancer cells is a mitochondrial and
      caspase-mediated process and whether it is dependent on nuclear factor kappaB
      transcriptional activity. METHODS: Previously described H157 non-small cell lung
      cancer cells were treated with gemcitabine, and DNA fragmentation was determined.
      Caspase 3, 6, 7, 8, and 9 activity in cytoplasmic extracts was determined
      fluorometrically. The mitochondrial permeability index and cytosolic cytochrome c
      levels were also determined. The caspase inhibitor Boc-D, as well as nuclear
      factor kappaB-regulated gene products A1, c-IAP-2, and Bcl-X(L), were added to
      H157 cells lacking nuclear factor kappaB and the degree of apoptosis assessed.
      All experiments were performed in triplicate, and data significance was
      determined by means of analysis of variance. RESULTS: Non-small cell lung cancer
      cells lacking functional nuclear factor kappaB (H157I) underwent more apoptosis
      after chemotherapy than vector control cells (H157V). There was an increase in
      the mitochondrial permeability index and cytochrome c release after chemotherapy
      in the H157I cells. H157I cells also had more activation of caspases 3 and 9 than
      control cells. Inhibition of caspase activity or transfection with nuclear factor
      kappaB-regulated gene products rescued cell death after the inhibition of nuclear
      factor kappaB. CONCLUSION: Chemosensitization by means of inhibition of nuclear
      factor kappaB in non-small cell lung cancer cells occurs through increased
      cytochrome c release and caspase 3 and 9 activation. Inhibition of nuclear factor
      kappaB or its gene products in addition to chemotherapy warrants further study as
      a treatment strategy in patients with advanced-stage non-small cell lung cancer.

PMID- 11828292
TI  - Risk factor analysis for proximal and distal reoperations after surgery for acute
      type A aortic dissection.
AB  - OBJECTIVE: This study was undertaken to determine significant risk factors for
      proximal or distal reoperations after surgical correction of acute type A aortic
      dissection. METHODS: Between 1980 and 2000, a total of 160 consecutive patients
      (mean age 57.5 +/- 13.3 years, 126 men) underwent surgery for acute type A aortic
      dissection. Proximal repair was performed by means of ascending aorta replacement
      with valve resuspension in 130 cases (81.3%), composite graft replacement in 19
      cases (11.9%), separate aortic valve and ascending aorta replacement in 7 cases
      (4.4%), and aortic repair in 1 case (0.6%). Distal repair required arch
      replacement in 23 cases. Follow-up time averaged 4.51 +/- 5.6 years per patient.
      RESULTS: Survival estimates after initial operation were 66.1% +/- 3.8%, 57.7% +/
      4.2%, 52.2% +/- 4.6%, and 42.5% +/- 5.8% at 1, 5, 10, and 15 years,
      respectively. Thirty patients required 37 reoperations at a mean interval of 5.7
      +/- 4.5 years after the initial operation. Freedoms from reoperation were 96.9%
      +/- 1.8%, 74.7% +/- 5.3%, 60.8% +/- 6.8%, and 39.3% +/- 9.1% at 1, 5, 10, and 15
      years, respectively. Reoperations included procedures on the proximal aorta
      (aortic root or valve) in 21 cases and on the distal aorta or its side branches
      in 19 cases. Cox regression analysis distinguished severe preoperative aortic
      valve insufficiency as the only significant risk factors for proximal
      reoperation; younger patient age, more distal extent of dissection, and more
      recent operative date were found to be significant risk factors for distal
      reoperation. CONCLUSION: Patients with acute type A aortic dissection who have
      severe aortic valve insufficiency are at increased risk for proximal reoperation.
      These patients should benefit from a more aggressive proximal repair at initial
      operation. Distal extent of aortic resection at initial operation did not
      significantly influence the risk of distal reoperation.

PMID- 11828294
TI  - Aortic valve cusp vessel density: relationship with tissue thickness.
AB  - OBJECTIVES: The presence of a microvasculature within aortic cusps implies that
      tissue oxygen requirements exceed the amount deliverable by diffusion from the
      tissue surfaces alone. For the design of a successful tissue-engineered valve
      replacement, the effect of diffusion distance (tissue thickness) on oxygen
      delivery must be considered. We therefore examined in normal aortic valve cusps
      the relationship between the presence of microvessels and the tissue thickness.
      METHODS: Thirty porcine aortic valve cusps were excised and examined after cusp
      microvessels were pressure filled with a carbon particle solution. Cusp images
      were captured for stereographic vessel density analysis, and cusp thickness was
      determined with a radiographic technique. Histologic cross-sections were
      evaluated to determine vessel depth from the cusp surface. RESULTS: Cusp basal
      regions measured 0.69 to 0.86 mm in thickness, significantly thicker (P =.001)
      than the rest of the cusp, which measured 0.36 to 0.48 mm. In general a vascular
      bed was present when cusp thickness exceeded 0.5 mm, with a median value of 5.16
      vessels/mm(3). CONCLUSIONS: From published values of arterial wall oxygen
      consumption and diffusivity, we predicted that the probable maximum oxygen
      diffusion distance for valve tissue would be about 0.2 mm. This was consistent
      with our physical findings, which implies that central tissue anoxia is avoided
      by the capillary bed. An avascular tissue-engineered valve metabolically similar
      to an aortic valve should therefore not exceed a thickness of approximately 0.40
      mm.

PMID- 11828293
TI  - Vancomycin versus cefazolin prophylaxis for cardiac surgery in the setting of a
      high prevalence of methicillin-resistant staphylococcal infections.
AB  - OBJECTIVE: This study was undertaken to compare the efficacy of vancomycin
      prophylaxis with that of cefazolin in preventing surgical site infections in a
      tertiary medical center with a high prevalence of methicillin-resistant
      staphylococcal infections. METHODS: All adult patients (> or = 18 years)
      scheduled for cardiac surgery requiring sternotomy were randomly assigned to
      receive vancomycin (1 g every 12 hours) or cefazolin (1 g every 8 hours).
      Prophylaxis was started during the induction of anesthesia and continued for only
      24 hours. Patients were followed up for at least 30 days (1 year for those
      receiving a cardiac implant). Surgical site infections were stratified according
      to the National Nosocomial Infections Surveillance System risk index. RESULTS: Of
      the 885 patients included in the study, 452 received vancomycin and 433 received
      cefazolin. The overall surgical site infection rates were similar in the two
      groups (43 cases in the vancomycin group, 9.5%, vs 39 cases in the cefazolin
      group, 9.0%, P =.8). Superficial and deep incisional surgical site infection
      rates were also similar in the two groups. There was a trend toward more frequent
      organ-space infections and infections with beta-lactam-resistant organisms among
      patients receiving cefazolin, but this trend did not reach statistical
      significance. In contrast, surgical site infections caused by methicillin
      susceptible staphylococci were significantly more common in the vancomycin group
      (17 cases, 3.7%, vs 6 cases, 1.3%, P =.04). The durations of postoperative
      hospitalization and the mortalities were similar in the two groups. CONCLUSIONS:
      This trial suggests that vancomycin and cefazolin have similar efficacy in
      preventing surgical site infections in cardiac surgery.

PMID- 11828295
TI  - Unconventional vessel wall apposition in off-pump porcine coronary artery bypass
      grafting: low versus high graft flow.
AB  - OBJECTIVE: Facilitated coronary anastomosis techniques may involve unconventional
      vessel wall apposition in contrast to standard intima-intima apposition. We
      assessed the patency, anastomotic thrombus formation, and intimal hyperplasia of
      unconventional intima-adventitia apposition versus conventional suturing
      techniques in beating heart coronary bypass grafting under low versus high graft
      flow conditions. METHODS: The intima-adventitia (n = 28) and conventional
      anastomoses (n = 28) were evaluated intraoperatively (n = 56), at 4 hours (n =
      20), and at 5 weeks (n = 36) in a new off-pump low-flow (n = 28) and high-flow (n
      = 28) porcine bypass model (< or = 15 mL/min and about 60 mL/min, respectively).
      The anastomoses were assigned to the animals by means of randomized
      stratification and examined by means of flow measurements, angiography, and
      histology. RESULTS: Mean graft flows in intima-adventitia and in conventional
      anastomoses were similar (P =.709). All but 1 of 56 anastomoses (low flow
      conventional) were fully patent at the time of death. At 4 hours, only small
      platelet depositions were found at the exposed media and adventitia in the
      unconventional anastomoses. At 5 weeks, little streamlining intimal hyperplasia
      was found, which was comparable between the anastomoses (P =.600). CONCLUSIONS:
      In low-flow conditions (< or = 15 mL/min) unconventional intima-adventitia
      apposition was not detrimental to the internal thoracic-coronary artery
      anastomosis in the pig. This finding may expand design strategies of facilitated
      coronary artery bypass anastomosis techniques.

PMID- 11828296
TI  - Quadricuspid aortic valve in transposition of the great arteries.

PMID- 11828297
TI  - Anatomic relationship of the coronary orifice and truncal valve in truncus
      arteriosus and their surgical implication.

PMID- 11828298
TI  - Intrapericardial diaphragmatic hernia and atrial septal defect in adults.

PMID- 11828299
TI  - Extended total arch replacement by means of the open stent-grafting method to
      treat intimal tears after transluminal stent-graft placement for a ruptured acute
      type B aortic dissection.

PMID- 11828300
TI  - Endoscope-assisted superior septal approach for resection of left atrial myxoma.

PMID- 11828301
TI  - Strangulated giant transdiaphragmatic hernia: a rare complication of coronary
      artery bypass grafting with the right gastroepiploic artery.

PMID- 11828302
TI  - Aortic cross-sectional area/height ratio timing of aortic surgery in asymptomatic
      patients with Marfan syndrome.

PMID- 11828303
TI  - Treatment of iatrogenic acute mitral regurgitation.

PMID- 11828304
TI  - Hybrid endovascular stent grafting for aortic arch aneurysm with aortopulmonary
      fistula.

PMID- 11828305
TI  - Juxtaductal coarctation with type B dissection of the aorta: a new operative
      technique.

PMID- 11828306
TI  - Heart herniation after blunt chest trauma.

PMID- 11828307
TI  - Transapical aortic cannulation for acute aortic dissection with diffuse
      atherosclerosis.

PMID- 11828308
TI  - Stent-graft-induced intimal injury one year after surgery.

PMID- 11828309
TI  - Tuberculous aneurysm of the descending thoracic aorta.

PMID- 11828310
TI  - Backtable ventricular and atrial septal defect repair of an Eisenmenger allograft
      with concomitant domino heart transplantation.

PMID- 11828311
TI  - Valve-sparing aortic root replacement in patients after a previous operation for
      acute type A aortic dissection.

PMID- 11828312
TI  - A new concept in distal arch aneurysm repair with a stent graft.

PMID- 11828313
TI  - Effects of cardiopulmonary bypass on narrow-pore flow behavior of blood.

PMID- 11828314
TI  - Successful use of activated recombinant factor VII to control bleeding
      abnormalities in a patient with a left ventricular assist device.

PMID- 11828315
TI  - Apical transthoracic Doppler echocardiography can be useful for analysis of
      postoperative early function of the left internal thoracic artery.

PMID- 11828316
TI  - Analysis of edema fluids and histologic features of the lung in reexpansion
      pulmonary edema during video-assisted thoracoscopic surgery.

PMID- 11828317
TI  - Living-donor lobar lung transplantation for bronchiolitis obliterans after
      Stevens-Johnson syndrome.

PMID- 11828318
TI  - The treatment of Askin tumor: results of two cases.

PMID- 11828319
TI  - Operation for acute type A aortic dissection in octogenarians: is it justified?

PMID- 11828320
TI  - Alkalosis induced by alpha-stat management: cause of neuronal injury after deep
      hypothermic circulatory arrest?

PMID- 11828321
TI  - Preoperative assessment of hand circulation by means of Doppler ultrasonography
      and the modified Allen test.

PMID- 11828322
TI  - Regulation of Lck activity by CD4 and CD28 in the immunological synapse.
AB  - Although the Src family tyrosine kinase Lck is essential for T cell receptor
      (TCR) signaling, whether or how Lck is activated is unknown. Using a
      phosphospecific antiserum to Lck, we show here that Lck becomes
      autophosphorylated when T cells are stimulated by antigen-presenting cells
      (APCs). We found that TCR cross-linking alone could not stimulate Lck
      autophosphorylation and CD45 was not required for this process. Instead, the T
      cell accessory molecules CD4 and CD28 cooperated to induce autophosphorylation of
      Lck. CD4 recruited Lck to the T cell--APC interface, whereas CD28 sustained Lck
      activation. These data show how the multiple interactions afforded by the
      immunological synapse drive efficient and highly specific signaling.

PMID- 11828323
TI  - Visualizing priming of virus-specific CD8+ T cells by infected dendritic cells in
      vivo.
AB  - The rational design of vaccines that elicit CD8+ T cell responses requires
      knowledge of the identity of the antigen-presenting cell (APC), the location and
      time of presentation and the nature of the antigen presented by the APC. Here we
      address these questions for an antigen encoded by a recombinant vaccinia virus.
      We found that, following local infection, vaccinia virus infected macrophages and
      dendritic cells in draining lymph nodes. However, only the dendritic cells
      presented antigen to naive CD8+ T cells, as determined by direct visualization of
      sectioned nodes by confocal microscopy. Presentation occurred as rapidly as 6 h
      after inoculation and quickly declined in parallel with the number of infected
      cells present in the nodes. These data provide direct evidence that virus
      infected APCs prime naive CD8+ T cells in vivo.

PMID- 11828324
TI  - Dysregulation of T lymphocyte function in itchy mice: a role for Itch in TH2
      differentiation.
AB  - Itch is an E3 ubiquitin ligase that is disrupted in nonagouti-lethal or itchy
      mice. Itch deficiency leads to severe immune and inflammatory disorders and
      constant itching of the skin. Here we show that Itchminus sign/minus sign T cells
      show an activated phenotype and enhanced proliferation. Production of the type 2
      T helper (TH2) cell cytokines interleukin 4 (IL-4) and IL-5 by Itchminus
      sign/minus sign T cells was augmented upon stimulation, and the TH2-dependent
      serum concentrations of immunoglobulin G1 (IgG1) and IgE in itchy mice were also
      increased. Molecularly, Itch associated with and induced ubiquitination of JunB,
      a transcription factor that is involved in TH2 differentiation. These results
      provide a molecular link between Itch deficiency and the aberrant activation of
      immune responses in itchy mice.

PMID- 11828325
TI  - Structural basis for CDK6 activation by a virus-encoded cyclin.
AB  - Cyclin from herpesvirus saimiri (Vcyclin) preferentially forms complexes with
      cyclin-dependent kinase 6 (CDK6) from primate host cells. These complexes show
      higher kinase activity than host cell CDKs in complex with cellular cyclins and
      are resistant to cyclin-dependent inhibitory proteins (CDKIs). The crystal
      structure of human CDK6--Vcyclin in an active state was determined to 3.1 A
      resolution to better understand the structural basis of CDK6 activation by viral
      cyclins. The unphosphorylated CDK6 in complex with Vcyclin has many features
      characteristic of cyclinA-activated, phosphorylated CDK2. There are, however,
      differences in the conformation at the tip of the T-loop and its interactions
      with Vcyclin. Residues in the N-terminal extension of Vcyclin wrap around the tip
      of the CDK6 T-loop and form a short beta-sheet with the T-loop backbone. These
      interactions lead to a 20% larger buried surface in the CDK6--Vcyclin interface
      than in the CDK2--cyclinA complex and are probably largely responsible for the
      specificity of Vcyclin for CDK6 and resistance of the complex to inhibition by
      INK-type CDKIs.

PMID- 11828326
TI  - A pre-translocational intermediate in protein synthesis observed in crystals of
      enzymatically active 50S subunits.
AB  - The large ribosomal subunit catalyzes peptide bond formation during protein
      synthesis. Its peptidyl transferase activity has often been studied using a
      'fragment assay' that depends on high concentrations of methanol or ethanol. Here
      we describe a version of this assay that does not require alcohol and use it to
      show, both crystallographically and biochemically, that crystals of the large
      ribosomal subunits from Haloarcula marismortui are enzymatically active. Addition
      of these crystals to solutions containing substrates results in formation of
      products, which ceases when crystals are removed. When substrates are diffused
      into large subunit crystals, the subsequent structure shows that products have
      formed. The CC-puromycin-peptide product is found bound to the A-site and the
      deacylated CCA is bound to the P-site, with its 3prime prime or minute OH near N3
      A2486 (Escherichia coli A2451). Thus, this structure represents a state that
      occurs after peptide bond formation but before the hybrid state of protein
      synthesis.

PMID- 11828327
TI  - MRI of the postoperative shoulder.
AB  - Performing and interpreting MRI of the shoulder in patients after surgery is a
      difficult task. The normal anatomic features are distorted by the surgical
      alterations as well as the artifacts that result from metal and other materials
      used in the surgical procedures. This article reviews the common surgical
      procedures undertaken in patients with rotator cuff disease and shoulder
      instability, and how they affect the appearance of the relevant anatomic
      structures on MRI examination. It also reviews the more common causes for
      residual and recurrent abnormalities seen in such patients and how MRI can be
      used to diagnose such lesions, thus aiding the orthopedic surgeon in treating
      these difficult clinical problems.

PMID- 11828328
TI  - Imaging findings in Mazabraud's syndrome: seven new cases.
AB  - OBJECTIVE: To present seven new cases of Mazabraud's syndrome with particular
      observations on the magnetic resonance imaging findings and a review of the
      literature. DESIGN AND PATIENTS: A multi-institutional retrospective review was
      performed on seven patients with confirmed Mazabraud's syndrome. The patient
      group was composed of six women and one man, ranging in age from 39 to 65 years,
      with a mean age of 53 years. RESULTS: Fibrous dysplasia was more often
      polyostotic ( n=6) and right-sided ( n=4). Fibrous dysplasia involved the femur
      in five cases. The soft tissue myxomas were multiple in four cases and were
      intramuscular in origin. The most commonly affected location was the thigh (
      n=4). On computed tomography, myxomas were well-circumscribed, low-attenuation
      masses. On magnetic resonance images, the lesions were significantly low in
      signal intensity on T1-weighted images and high in signal intensity on T2
      weighted images relative to adjacent skeletal muscle. Enhancement of the myxomas
      was heterogeneous with irregular, peripheral rim enhancement, and a variable
      degree of central enhancement depending on the abundance of solid myxoid tissue
      and bridging fibrous septa. CONCLUSIONS: Knowledge of Mazabraud's syndrome and
      the imaging appearance of intramuscular myxoma is important in order to avoid
      unnecessary biopsies of the osseous and soft tissue lesions. The unique features
      of this disorder allow discrimination from soft tissue malignancies such as
      sarcoma.

PMID- 11828329
TI  - Chondroblastoma and clear cell chondrosarcoma: radiological and MRI
      characteristics with histopathological correlation.
AB  - OBJECTIVE: To analyze and compare the radiological and magnetic resonance imaging
      (MRI) appearances of chondroblastoma and clear cell chondrosarcoma with
      histopathological correlation. DESIGN AND PATIENTS: Twelve patients with
      histologically proven chondroblastoma and of another four patients with clear
      cell chondrosarcoma were investigated by radiographs and MRI (T1-, T2-weighted
      sequences, intravenous gadolinium application). Additionally, the clinical and
      radiologic data of seven cases of clear cell chondrosarcoma without available MRI
      were considered. The localization, calcification of tumor matrix, periosteal
      reaction, cortical bone and patterns of bone destruction were analyzed according
      to the Lodwick radiological grading system (LRGS). The signal intensity on T1-
      and T2-weighted sequences, characteristics of contrast enhancement, associated
      bone marrow edema, soft tissue reaction and joint involvement were evaluated.
      Histopathological specimens were available in all cases. RESULTS: The age of
      patients with chondroblastoma (range 15-59 years, mean 22.3 years) was lower than
      that of those with clear cell chondrosarcoma (range 19-61 years, mean 36.6
      years), and the lesions were smaller in the chondroblastoma group (range 1-4 cm,
      mean 2.3 cm) than in patients with clear cell chondrosarcoma (range 3-7.5 cm,
      mean 5.2 cm). The chondroblastomas were more confined to the epiphysis (10/12)
      than the clear cell chondrosarcomas. All chondroblastomas and clear cell
      chondrosarcomas except one were classified as grade 1A or 1B according to the
      LRGS; one clear cell chondrosarcoma was judged as grade 2. Signal intensity of
      the tumors on MRI was very heterogeneous in both groups. High signal intensity on
      T2-weighted MR images in chondroblastoma mostly corresponded to areas with
      aneurysmal bone cyst components and in clear cell chondrosarcoma to islands of
      hyaline cartilage. Contrast enhancement occurred in all tumors and tended to be
      more intense with clear cell chondrosarcoma. Chondroblastoma was more frequently
      associated with bone marrow edema (11/12), periosteal reaction (10/12), soft
      tissue reaction (7/12) and synovitis (3/12). CONCLUSION: Chondroblastoma occurs
      in younger patients, is smaller than clear cell chondrosarcoma and is more
      confined to the epiphysis. The overlap of signal intensity and contrast
      enhancement patterns does not allow a reliable differentiation of the two tumors
      by MRI. Chondroblastomas are typically associated with bone marrow edema,
      periosteal reaction and soft tissue reaction.

PMID- 11828330
TI  - Role of computed tomography in the diagnosis of rib and lung involvement in
      tuberculous retromammary abscesses.
AB  - OBJECTIVE: To assess the role of computed tomography (CT) in the diagnosis of rib
      and lung involvement in tuberculous abscess in the retromammary region. DESIGN
      AND PATIENTS: Eight patients with tuberculous retromammary abscess were examined
      by CT and the findings were evaluated. A cold abscess (purulent collection with
      absence of acute inflammation) was aspirated in all cases. Diagnosis was
      confirmed by acid-fast bacillus culture, or histologic examination. RESULTS: CT
      showed a relatively well marginated, inhomogeneous, hypodense lesions in all
      eight cases. Following administration of intravenous contrast medium, these
      lesions showed enhancing walls, suggestive of an infective collection. Lung
      involvement was seen in one patient. A direct communication from the retromammary
      lesion through the thoracic wall into the pleura was seen in five cases. In four
      cases destroyed rib fragments within the abscess were noted. CONCLUSION: A
      tuberculous abscess in the retromammary region is usually shown on CT as a focal,
      well-marginated, inhomogeneous, hypodense lesion with a surrounding enhancing
      rim. A direct communication with the pleura, a destroyed rib fragment in the
      abscess, and associated lung involvement may be revealed by CT.

PMID- 11828331
TI  - Spontaneous regression of malignant lymphoma of the lumbar spine.
AB  - Spontaneous regression of diffuse B-cell type lymphoma of the lumbar vertebra is
      reported. A 61-year-old woman experienced spontaneous disappearance of a large
      psoas mass associated with an infiltrating process of the lumbar vertebrae. The
      biopsy of the residual change after spontaneous regression revealed reactive
      foamy histiocytes and small lymphocytes with no atypia. The lesion recurred 7
      months later with no systemic treatment in the interim, when the diagnosis of
      lymphoma was finally made. Spontaneous regression may be related to potentiation
      of the host immune response, which affects tumor growth.

PMID- 11828332
TI  - Malignant transformation of fibrous dysplasia into chondroblastic osteosarcoma.
AB  - A case of malignant transformation of polyostotic fibrous dysplasia into
      maxillary chondroblastic osteosarcoma is presented. The clinical, radiographic,
      CT, MR imaging features and pathological findings of polyostotic fibrous
      dysplasia and its malignant transformation are described. Malignant
      transformation of fibrous dysplasia is rare and has not previously been described
      in the English literature in this location in McCune-Albright syndrome and in the
      absence of radiation treatment.

PMID- 11828333
TI  - Fibroblastic osteosarcoma of the mandible.
AB  - Osteosarcoma of the mandible is a rare lesion. We report the case of a 16-year
      old male who developed a fibroblastic osteosarcoma at the site of a wisdom tooth
      extraction. The lesion followed an aggressive course of recurrence and diffuse
      disseminated osteosarcomatosis. We speculate on the causal factors that resulted
      in this rapid course.

PMID- 11828334
TI  - Solitary juxtacortical neurofibroma of the humerus.
AB  - A neurofibroma as a discrete, superficial tumor of a long bone has been described
      only once in the world literature. We report the radiologic findings of a case of
      a juxtacortical neurofibroma.

PMID- 11828335
TI  - Stress fracture of the ulna in an adolescent baton twirler.
AB  - Upper extremity stress fractures are rare, with the majority of those reported
      occurring in the ulna. The location of the fracture is influenced by the type of
      activity and mechanism of injury with which it is associated. We report the first
      case of a mid-ulnar stress fracture in a baton twirler due to chronic torsional
      stress. This patient was referred to our Orthopedic Oncology clinic with a
      preliminary diagnosis of osteoid osteoma.

PMID- 11828336
TI  - Distinguishing multiple rice body formation in chronic subacromial-subdeltoid
      bursitis from synovial chondromatosis.
AB  - Multiple rice body formation is a complication of chronic bursitis. Although it
      resembles synovial chondromatosis clinically and on imaging, the literature
      suggests that analysis of radiographic and MR appearances should allow
      discrimination. We report the imaging findings in a 41-year-old man presenting
      with rice body formation in chronic subacromial-subdeltoid bursitis. We found
      that the signal intensity of the rice bodies is helpful in making the diagnosis.

PMID- 11828337
TI  - Primary synovial osteochondromatosis of the first metatarsophalangeal joint.
AB  - Synovial osteochondromatosis is an uncommon disorder, generally seen in large
      joints such as the knee, elbow, shoulder, hip and ankle. We report a 35-year-old
      man with synovial osteochondromatosis of the metatarsophalangeal joint of the
      great toe. Despite the rarity of the location, the radiographic appearance ought
      to suggest the diagnosis. Histological confirmation is required, since malignancy
      cannot be totally ruled out clinically and radiographically.

PMID- 11828338
TI  - Acral synovial chondrosarcoma.
AB  - Acral chondrosarcoma is rare. Synovial chondrosarcoma is even rarer. Synovial
      chondrosarcoma arising without evidence of pre-existing or concurrent synovial
      chondromatosis is exceedingly rare. We present a case of acral synovial
      chondrosarcoma involving both sides of the metacarpophalangeal joint of the thumb
      in a 69-year-old man. Radiographically, the lesion mimicked gout. On MR imaging,
      the lobulated contours of the soft tissue mass suggested synovial chondromatosis.
      Histological examination revealed a chondrosarcoma, which on the basis of imaging
      findings we present as having arisen from the synovium. The tumor invaded a
      portion of the cartilage of the metacarpophalangeal joint and equally destroyed
      the bones of the distal metacarpal and base of the proximal phalanx of the thumb,
      while sparing the bony joint surfaces.

PMID- 11828340
TI  - Association between single-nucleotide polymorphisms in selectin genes and
      immunoglobulin A nephropathy.
AB  - Although intensive efforts have been undertaken to elucidate the genetic
      background of immunoglobulin A nephropathy (IgAN), genetic factors associated
      with the pathogenesis of this disease are still not well understood. We designed
      a case-control association study that was based on linkage disequilibrium among
      single-nucleotide polymorphisms (SNPs) in the selectin gene cluster on chromosome
      1q24-25, and we found two SNPs in the E-selectin gene (SELE8 and SELE13) and six
      SNPs in the L-selectin gene (SELL1, SELL4, SELL5, SELL6, SELL10, and SELL11) that
      were significantly associated with IgAN in Japanese patients. All eight SNPs were
      in almost complete linkage disequilibrium. SELE8 and SELL10 caused amino acid
      substitutions from His to Tyr and from Pro to Ser (chi2=9.02, P=.0026, odds ratio
      = 2.73 [95% confidence interval [CI] 1.38--5.38] for His-to-Tyr substitutions;
      chi2=17.4, P=.000031, odds ratio = 3.61 [95% CI 1.91--6.83] for Pro-to-Ser
      substitutions), and SELL1 could affect promoter activity of the L-selectin gene
      (chi2=19.5, P=.000010, odds ratio = 3.77 [95% CI 2.02--7.05]). The TGT haplotype
      at these three loci was associated significantly with IgAN (chi2=18.67,
      P=.000016, odds ratio = 1.88 [95% CI 1.41--2.51]). Our results suggest that these
      eight SNPs in selectin genes may be useful for screening populations susceptible
      to the IgAN phenotype that involves interstitial infiltration.

PMID- 11828342
TI  - Practical management of posterolateral instability of the knee.

PMID- 11828341
TI  - Alternative splicing in the alpha-galactosidase A gene: increased exon inclusion
      results in the Fabry cardiac phenotype.
AB  - Fabry disease is an inborn error of glycosphingolipid catabolism, resulting from
      deficient activity of lysosomal alpha-galactosidase A (alpha-Gal A). A rare
      alternative splicing that introduces a 57-nucleotide (nt) intronic sequence to
      the alpha-Gal A transcript from intron 4 of the gene has been identified. In
      addition, a novel midintronic base substitution that results in substantially
      increased alternative splicing has been identified in a patient with Fabry
      disease who has the cardiac variant phenotype. The sequence of the patient's
      intron 4 contains a single G-->A transversion at genomic nt 9331 (IVS4+919 G-->A
      ), located at the minus sign4 position of the 3' end of the intronic insertion
      (nts 9278--9334 in the genomic sequence). Minigene constructs containing the
      entire intron 4 sequence with G, A, C, or T at nt 9331 within an alpha-Gal A
      complementary DNA expression vector were prepared and expressed in COS-1 cells.
      Whereas transfection of the G or T minigenes transcribed predominantly normal
      sized transcripts, the transfection of the A or C minigenes produced a large
      amount of the alternatively spliced transcript. These results suggest that the G-
      >A mutation, within an A/C-rich domain, results in increased recognition of the
      alternative splicing by an A/C-rich enhancer-type exonic splicing enhancer. The
      intronic mutation was not observed in 100 unrelated unaffected men but was
      present in 6 unrelated patients with cardiac Fabry disease. Reverse-transcriptase
      polymerase chain reaction of total RNA of various normal human tissues revealed
      that the alternatively spliced transcript was present in all of the samples, and
      especially at a higher ratio in the lung and muscle. The normal transcript was
      present in the patients' lymphoblasts and resulted in approximately 10% residual
      enzyme activity, leading to a cardiac phenotype of Fabry disease.

PMID- 11828343
TI  - Update on advanced surgical techniques in the treatment of traumatic focal
      articular cartilage lesions in the knee.
AB  - Considerable interest has been developed over the past several years in expanding
      the treatment of symptomatic femoral condylar articular cartilage lesions in
      active patients. Multiple surgical techniques have been reported and evolving
      technologies, equipment and approaches continue to expand. The purpose of this
      paper is to review the presentation of focal articular cartilage lesions
      including treatment indications, current surgical options and postoperative
      protocols emphasizing advanced techniques used to preserve or restore hyaline
      cartilage tissue. The various surgical options are discussed and the advantages
      and disadvantages are reviewed and highlighted in a clinical practice guideline
      algorithm.

PMID- 11828344
TI  - Meniscus: Resection, repair, and replacement.

PMID- 11828345
TI  - Current applications for arthroscopic thermal surgery.

PMID- 11828346
TI  - Complex topics in arthroscopic subacromial space and rotator cuff surgery.

PMID- 11828347
TI  - Controversial topics in shoulder arthroscopy.
AB  - This is a review of the symposium entitled Controversial Topics in Shoulder
      Arthroscopy 2001, presented at the Arthroscopy Association of North America 20th
      Annual Meeting in Seattle, Washington in April of 2001. The covered topics
      include micro-instability, partial thickness rotator cuff tears, pathology of the
      biceps tendon, and thermal capsulorrhaphy.

PMID- 11828348
TI  - New frontiers in arthroscopic treatment of glenohumeral instability.

PMID- 11828349
TI  - Complications associated with arthroscopic shoulder surgery.
AB  - We review the literature on complication of arthroscopic shoulder surgery and
      their management. Computer data based searches were used to identify articles
      regarding complications of shoulder arthroscopy, as well as hand searches of
      Arthroscopy and Journal of Shoulder and Elbow Surgery over the last decade.
      Arthroscopic shoulder surgery has become a popular therapeutic and diagnostic
      procedure during the past two decades. As with all interventions complications
      can occur which require recognition and management by the orthopedic surgeon.
      While the literature is helpful with identifying types of complications,
      establishing the rate of these complications remains elusive. These complications
      can be divided into general complications, complications generic to all shoulder
      procedures, and complications specific to the type of procedure performed.
      General complications such as infection and anesthesia problems continue to show
      low incidences. Shoulder arthroscopy presents increased risk of complications
      over knee arthroscopy in regard to vascular and neurologic injury, fluid
      extravasation, stiffness, iatrogenic tendon injury, and equipment failure. New
      techniques of increased complexity for subacromial surgery, rotator cuff repair,
      and arthroscopic instability present new problems related to implant failure,
      nerve injury, iatrogenic fracture, and capsular necrosis. While the rate of
      complications especially with newer procedures remain elusive, most studies
      suggest that the rate is low, 5.8-9.5% in all recent review studies published.
      Underreporting complications makes assessment of incidence rates of complication
      difficult. Proper patient selection, attention to operative detail, and careful
      post-operative monitoring can minimize the morbidity associated with these
      complications.

PMID- 11828350
TI  - Coding and reimbursement in arthroscopic surgery.

PMID- 11828351
TI  - Prostate cancer and the educated consumer.

PMID- 11828352
TI  - Prostate cancer incidence, mortality, and survival trends in the United States:
      1981-2001.
AB  - The increased use of prostate-specific antigen (PSA) in screening for preclinical
      disease after 1985 is thought to be a major determinant of the changing patterns
      in prostate cancer incidence; however, the long-term effect of screening on
      future trends in mortality and survival is uncertain. This article reviews the
      temporal trends (1981-1998) for prostate cancer incidence, mortality, and
      survival, and projects prostate cancer incidence and mortality rates for 1999 to
      2001. Autoregressive, quadratic, time-series models were used to describe
      prostate cancer mortality rates in the US population and prostate cancer
      incidence rates derived from the National Cancer Institute's (NCI) Surveillance,
      Epidemiology and End Results (SEER) program. These models were based on data
      collected from 1979 through 1998, with forecasts produced for 1999 to 2001.
      Prostate cancer incidence increased steadily from 1981 to 1989, with a steep
      increase in the early 1990s, followed by a decline. Incidence rates were
      forecasted to remain stable through the year 2001. Mortality rates decreased
      steadily and were forecasted to continue to decrease concurrently with increasing
      5- and 10-year relative survival rates. The incidence, mortality, and survival
      trends were comparable in US blacks, who exhibited on average 2-fold higher
      mortality and 50% higher incidence than whites. Decreasing prostate cancer
      mortality and increasing relative survival trends in the United States were
      described after the introduction of PSA screening. However, the exaggerated rate
      of increase in the early 1990s in prostate cancer incidence was transient and
      likely a result of increased detection of preclinical disease that was prevalent
      in the general population.

PMID- 11828353
TI  - Clarifying uncertainty regarding detection and treatment of early-stage prostate
      cancer.
AB  - Detection and treatment of prostate cancer can theoretically identify and cure a
      potentially disabling and deadly disease. However, controversy exists primarily
      because of the absence of randomized controlled trials (RCTs) documenting that
      these strategies improve survival and quality of life. In the absence of
      definitive information from RCTs, patients seek information and recommendations
      from many sources. Physicians have an opportunity to help patients and their
      families sort through the vast array of conflicting and confusing information.
      Rather then recommending for or against routine prostate-specific antigen (PSA)
      testing, physicians should provide men who are interested in prostate cancer
      testing, 50 years of age and older, and have a life expectancy of at least 10 to
      15 years, with balanced information about the potential benefits and established
      harms of screening, diagnosis, and treatment. Validated informational materials
      can effectively and efficiently promote shared decision making. For early
      prostate cancer detection, the minimum information should include: the likelihood
      that prostate cancer will be diagnosed, possibilities of false-positive and false
      negative results, anxiety associated with a positive test, and uncertainty
      regarding whether screening reduces the risk for death from prostate cancer. For
      men with localized prostate cancer, acceptable treatment options include radical
      prostatectomy, radiation therapy, cryotherapy, early androgen-suppression
      therapy, and watchful waiting. These are all considered acceptable options
      because data do not provide clear-cut evidence for the superiority of any 1
      treatment. The only RCT comparing surgery to watchful waiting, though of
      relatively small size and conducted before PSA testing, showed no difference in
      survival after 23 years of follow-up. Watchful waiting does not remove prostate
      cancer, may miss an opportunity to cure or delay disease progression, and may
      lead to increased patient anxiety. However, watchful waiting avoids the harmful
      side effects of early intervention and does provide palliative therapy if and
      when symptomatic disease progression occurs. Furthermore, intervention is not
      necessary in the vast majority of men because most prostate cancers do not cause
      mortality or serious morbidity. Therefore, quality of life in many men treated
      with watchful waiting is superior to those treated with early intervention. For
      the minority of men with prostate cancer likely to cause disability or death,
      early intervention options may not be effective. Although commonly used in other
      countries, watchful waiting is rarely recommended in the United States. The
      opportunity exists to resolve the confusion, close the gaps in knowledge, and
      enhance prostate cancer care by conducting RCTs. Until these RCTs are completed,
      physicians can assist patients by providing a balanced presentation of the known
      risks and potential but unproven benefits of detection and treatment options and
      incorporating patient preferences into health care decisions.

PMID- 11828354
TI  - Prostate biopsy techniques and indications: when, where, and how?
AB  - Transrectal ultrasound (TRUS) and prostate biopsy have become one of the most
      common office-based procedures for the practicing urologist. During the past 50
      years, the techniques, indications, and pathologic interpretation of prostate
      biopsies have evolved. The abandonment of blind finger-guided needle biopsies in
      favor of systematic TRUS-guided biopsies epitomizes much of this change.
      Similarly, the indications for prostate biopsy have become more refined. In the
      past, the presence of a prostatic nodule on digital rectal examination (DRE) was
      the primary indication for biopsy until the introduction of prostatic-specific
      antigen (PSA) in the 1980s and its widespread use for prostate cancer screening.
      Abnormalities of PSA or its derivatives now represent the most common indication
      for prostate biopsy. Although TRUS initially began as a tool to direct needles
      into various locations within the prostate, today a great deal of information can
      be obtained from prostate ultrasound for the discerning clinician. As such, TRUS
      guided biopsy of the prostate has become an important staging and diagnostic tool
      for the practicing urologist. Here we review the current techniques and
      indications as well as pertinent pathologic and staging data obtained through
      TRUS and prostate biopsy.

PMID- 11828355
TI  - Web resources for patients with prostate cancer: a starting point.
AB  - The information available on the World Wide Web is vast. Patients are becoming
      increasingly interested in resources available to them on the Internet for health
      and medical information. As the percentage of Americans with Internet access
      grows, health care providers are being asked by their patients to facilitate the
      search for quality information. This article provides the groundwork for
      urologists counseling their patients about Web-based information on prostate
      cancer. Internet sites that provide clear, in-depth information about symptoms
      and characteristics of prostate cancer, common tests performed, prevention, and
      treatment options are reviewed. Ten high-quality, patient-friendly Web sites that
      may be used as a resource for patients and physicians are presented.

PMID- 11828356
TI  - Relevant patient and tumor considerations for early prostate cancer treatment.
AB  - Prostate cancer remains the most commonly diagnosed noncutaneous malignancy in
      American men. Currently, there are 3 standard treatment options available to men
      with early prostate cancer: expectant management, radiation therapy, and radical
      prostatectomy. Although a number of studies have evaluated survival after
      treatment for early prostate cancer, the optimal choice of therapy for any given
      patient remains a difficult decision and requires the consideration of a variety
      of patient and tumor factors. The final selection of therapy for early prostate
      cancer should be based on an informed discussion between the physician and
      patient. To accomplish this goal, patients must be made familiar with the
      pertinent factors that affect survival. We review the factors most relevant for
      patients to understand as they consider their treatment options for early
      prostate cancer and summarize the data for physicians who counsel them.

PMID- 11828357
TI  - Prostate cancer support and advocacy groups: their role for patients and family
      members.
AB  - Patients and their families are profoundly affected by the diagnosis of prostate
      cancer. Competing treatment options and uncertainty regarding the expected course
      of their disease may provoke strong emotional reactions including depressive
      symptoms and feelings of overwhelming anxiety. Despite potentially significant
      implications regarding quality-of-life (QOL) issues associated with various forms
      of treatment, few studies have focused specifically on the psychologic reactions
      among men with the disease or their family members. In response to this critical
      lack of psychosocial information and care, many affected individuals turn to
      prostate cancer support or advocacy groups for their educational needs, coping
      strategies, assistance with concerns about medical decisions, and peer
      networking. This article summarizes the psychologic impact of a prostate cancer
      diagnosis on patients, spouses, and family members and reviews pertinent advocacy
      and support information available to men affected by this disease and the
      physicians who care for them.

PMID- 11828358
TI  - Decision-making strategies for patients with localized prostate cancer.
AB  - Patients diagnosed with early-stage prostate cancer not only have to cope with
      the impact of the cancer diagnosis, but also need to interpret complicated
      medical information to make an informed treatment decision. We report initial
      results from an ongoing longitudinal investigation examining treatment decision
      making among men diagnosed with early stage prostate cancer. Men (N = 654) were
      recruited into the assessment study after an initial treatment consultation with
      a urologic surgeon or radiation oncologist. Patients were, on average, 66 years
      old, married (85%), had at least a high school education (45%), were retired
      (58%), and were Caucasian (91%) or African American (7%). Guided by a cognitive
      affective theoretical framework, we assessed treatment and disease-relevant
      beliefs and affects in addition to clinical variables. The majority of patients
      decided on external beam radiation therapy (52%), followed by brachytherapy
      (25%), prostatectomy (17%), and watchful waiting (6%). Patients who decided on
      prostatectomy were significantly younger (mean age, 58 yr) than patients who
      received radiation therapy (mean age, 67 yr) and brachytherapy (mean age, 66 yr).
      When asked for the most important reason influencing their treatment decision,
      patients indicated physician recommendation (51%), advice from friends and family
      (19%), information obtained from books and journals (18%), or the Internet (7%).
      Among cognitive variables, patients who decided on surgery perceived prostate
      cancer as being significantly more serious (P <.001), and had greater
      difficulties in making a treatment decision (P <.005) compared with patients
      receiving radiation therapy or brachytherapy. Surgical patients were also more
      distressed about their treatment decision (P <.001) and concerned that the cancer
      might spread (P <.005). To date, patients followed-up after treatment have not
      indicated significant regrets about their therapeutic choice. These data suggest
      that unique treatment-related beliefs and affects need to be taken into account
      during the treatment counseling process. Implications for the development of
      decision aids are discussed.

PMID- 11828359
TI  - Treatment outcomes in localized prostate cancer: a patient-oriented approach.
AB  - Although there are many treatment options available to patients with localized
      prostate cancer, it remains unclear which is superior in terms of overall
      survival. Patients, therefore, consider a number of other less traditional
      outcomes when choosing therapy for newly diagnosed disease. In particular,
      because each treatment can have a unique and highly individual impact on various
      aspects of the patient's health and daily life, there is a need for a patient
      oriented approach to outcomes that accounts for both quantity and quality of life
      after therapy. Although all therapies can result in some degree of sexual,
      urinary, or bowel dysfunction, the degree of bother patients experience does not
      always correlate with the objective degree of symptoms present. Providers must,
      therefore, make the important distinction between function and bother when
      presenting the risks for each therapy to patients. Patients should also be aware
      that if they experience particular bother from their sexual or urinary
      dysfunction, there are therapies available that will improve erectile function or
      lower urinary tract voiding dysfunction and result in better quality of life.
      Finally, when discussing the probability of unwanted outcomes, such as urinary,
      sexual, or bowel dysfunction after treatment for localized prostate cancer,
      providers should strive to present risks by using a number of different styles,
      facilitating understanding, and leading to a truly informed decision that best
      fits the patient's goals.

PMID- 11828360
TI  - Shared decision-making strategies for early prostate cancer.
AB  - Prostate cancer remains one of the most prevalent and least understood of all
      human malignancies. Pathologic evidence suggests that neoplastic changes of the
      prostate epithelium begin early in a man's adult life, but do not become
      clinically evident or relevant until decades later. The natural history of this
      enigmatic disease is heterogeneous, ranging from a benign and indolent course to
      one that rapidly progresses, causing significant morbidity and mortality. The
      divergent aspects of prostate cancer are underscored by vast differences in
      incidence and mortality statistics, causing consternation among clinicians and
      patients regarding the relative value of early detection, screening, and
      treatment strategies. Competing risks and perceived benefits of proposed
      treatment options including surgery, radiation therapy, hormonal deprivation,
      watchful waiting, and newer technologies are complex. Given these uncertainties,
      how should patients integrate these data and what role must physicians play in
      the process? Here we present a summary of shared decision making for men with
      localized prostate cancer. We approach this task by using a clinical case
      scenario to discuss issues relating to incidence and mortality trends,
      uncertainty regarding natural history, biopsy techniques and concerns, relevant
      tumor and clinical data, patient information gathering through Web-based
      resources, as well as support and advocacy groups, outcomes implications, and
      methods patients use to approach treatment decisions. We present a unified
      platform for shared decision-making strategies regarding prostate cancer in
      clinical practice.

PMID- 11828365
TI  - Cytokine-mediated inhibition of apoptosis in non-transformed T cells and
      neutrophils can be dissociated from protein kinase B activation.
AB  - In the absence of survival-inducing cytokines activated T cells and neutrophils
      enter apoptosis spontaneously. Phosphatidylinositol 3-kinase (PI3 K) activation
      and signaling through PKB/AKT have been widely linked to the inhibition of
      apoptosis by cytokines. Here we have investigated the role of PKB in the
      inhibition of spontaneous apoptosis of activated human CD4+ T cells and
      neutrophils. We used a range of cytokines known to induce survival and/or
      activation of PKB. We found activation of PKB in T cells treated with IL-2 and
      insulin, and neutrophils cultured with N-formyl-Met-Leu-Phe (fMLP), insulin or
      granulocyte-macrophage colony-stimulating factor. Insulin did not inhibit
      apoptosis in neutrophils or T cells and fMLP did not delay neutrophil apoptosis.
      Intriguingly, IFN-beta induced PI3 K-dependent survival in both cell types, but
      did not activate PKB. IL-2 mediated rescue of T cells from apoptosis but no
      induction of proliferation occurred in thepresence of LY294002, an inhibitor of
      PI3 K, which also blocked subsequent PKB activation. The main role of PI3 K in IL
      2-mediated signaling may therefore be in the regulation of proliferation. These
      findings suggest that activation of PKB and inhibition of apoptosis can be
      dissociated in cytokine-mediated rescue of non-transformed CD4+ T cells and
      neutrophils.

PMID- 11828366
TI  - Distribution and regulation of expression of the putative human chemokine
      receptor HCR in leukocyte populations.
AB  - Human chemokine receptor (HCR) is a putative chemokine receptor sharing high
      similarity with CCR1, CCR2, CCR3 and CCR5. Its gene is located within the main
      cluster of CC-chemokine receptor genes, in the 3p21 region of the human genome.
      We generated monoclonal antibodies directed at human HCR, and studied its
      distribution in human leukocyte populations and cell lines, and its regulation
      following maturation or activation of these populations. In peripheral blood
      leukocytes, HCR is expressed on CD4+ and CD8+ T lymphocytes, including most
      memory and part of naive cells, but is absent from B cells. Expression of HCR was
      enhanced following stimulation of T cells by OKT3 and IL-2. HCR is present on
      monocytes and macrophages. Monocyte-derived dendritic cells harbored HCR, and
      expression was enhanced following stimulation by lipopolysaccharides, poly (I:C),
      IFN-gamma or CD40L. Neutrophils strongly expressed HCR. A similar distribution
      was found in bone marrow,and HCR was also expressed in CD34+ precursors.
      Expression of HCR and its regulation were confirmed by real-time PCR. In a panel
      of human tissues, we found abundant HCR transcripts in thymus, spleen, lymph
      nodes and lung. This large distribution across leukocyte populations, and the up
      regulation during DC maturation, represent a new profile among chemokine
      receptors. We speculate that HCR responds to inflammatory chemokines, and might
      be involved in the interaction between antigen presenting and T cells, and in
      hematopoiesis.

PMID- 11828367
TI  - Rat T cells express neither CD55 nor CD59 and are dependent on Crry for
      protection from homologous complement.
AB  - All human blood cells express decay-accelerating factor (DAF, CD55), CD59, and,
      with the exception of erythrocytes, membrane cofactor protein (MCP, CD46) to
      protect themselves from damage by the constant low-level activation of complement
      in serum. In rats and mice MCP is expressed only in testis, whereas DAF and CD59
      are broadly distributed. Rats and mice also express a unique complement
      regulator, Crry. Previously we have shown that DAF was absent from at least 75%
      of rat T cells. To further investigate this surprising finding, we assessed the
      expression levels of DAF, CD59 and Crry on all blood cell types in the rat. We
      found that Crry was abundantly expressed on all blood cells. CD59 was expressed
      abundantly on erythrocytes and granulocytes but was absent from all T cellsand
      platelets and a minority of B cells and NK cells. Double staining and depletion
      studies showed that T cells in all rat strains tested were DAF-CD59-.
      Neutralization of Crry using a blocking monoclonal antibody rendered T cells
      susceptible to lysis by homologous complement, indicating that Crry was solely
      responsible for protecting DAF-CD59- T cells from complement damage in the rat.

PMID- 11828368
TI  - IFN-gamma-producing CD45RA+CD8+ and IL-10-producing CD45RA-CD4+ T cells generated
      in response to LACK in naive subjects never exposed to Leishmania.
AB  - Leishmania guyanensis (L.g.)-specific CD8+ T cells can be isolated from PBMC of
      subjects who have never been previously exposed to Leishmania. Cells that produce
      IFN-gamma in response to live L.g. are generated from naive CD45RA+CD8+ T cells.
      The generation of L.g.-specific CD8+ T cells requires the presence of whole L.g.
      or UV-irradiated parasite but not the soluble antigens from L.g. promastigotes.
      The IFN-gamma-producing T cells recognize a specific antigen, the Leishmania
      homologue of receptors of activated C kinases (LACK) and this antigen but not
      live L.g. can produce a strong IL-10 response in CD45RA-CD4+ memory T cells from
      naive subjects. A single epitope (amino acid 156-173) is found to induce the IL
      10 synthesis. While the IFN-gamma-producing cells are present among CD45RA+CD8+ T
      cells that are CD62L-CDR7- and CLA-, the LACK-reactive IL-10-producing cells are
      CD4+ T cells that are CD62L+CCR7- and CLA-.

PMID- 11828369
TI  - 4-1BB (CD137) controls the clonal expansion and survival of CD8 T cells in vivo
      but does not contribute to the development of cytotoxicity.
AB  - 4-1BB is expressed on activated T cells. We analyzed the role of 4-1BB during the
      CD8 T cell response of OT-I TCR-transgenic T cells to ovalbumin. In vitro,
      blocking 4-1BB during peptide presentation reduced proliferation of naive CD8 T
      cells, but did not affect the generation of CTL. Using an in vivo adoptive
      transfer model, clonal expansion of CD8 T cells to whole protein in adjuvant was
      significantly reduced when 4-1BB was blocked, with 50-70% fewer CD8 T cells
      accumulating. This was due to a reduction in T cell division and to enhanced
      apoptosis of CD8 T cells that had undergone many divisions. T cells generated in
      the absence of 4-1BB were impaired in their ability to secrete IFN-gamma whereas
      CTL activity of the T cells that survived was unaffected. These findings
      demonstrate that 4-1BB contributes to clonal expansion, survival, and development
      of Tc1 cells when protein antigen is encountered by primary CD8 T cells in an
      inflammatory environment in vivo.

PMID- 11828370
TI  - Antibody modulation of antigen presentation: positive and negative effects on
      presentation of the tetanus toxin antigen via the murine B cell isoform of
      FcgammaRII.
AB  - Tetanus toxin has been a valuable model antigen to study the MHC class II
      restricted antigen processing pathway and is also frequently used to provide T
      helper determinants in vaccine formulations. To date most basic studies on the
      processing of this antigen have utilized human T and B cell clones. As a first
      step towards extending studies on this antigen into the murine system we have
      generated a panel of T cell clones and mAb in H-2(b) and H-2(d) mice. We
      investigated the presentation of tetanus toxin C fragment (TTCF) by the murine B
      cell lines LB27.4 (H-2(dxb)), A20 (H-2(d)) and IIA1.6 (H-2(d)) and the extent to
      which this could be modulated by the addition of mAb. One mAb, 10G5, induced
      strikingly enhanced presentation of T cell determinants located in the N-terminal
      region of TTCF while other antibodies inhibited presentation of these and other
      epitopes. The enhancing effects of the 10G5 antibody were blocked by the anti-FcR
      antibody 2.4G2 and were not observed in the FcR-negative IIA1.6 cell line.
      Interestingly, both FcgammaRIIB1 and FcgammaRIIB2 isoforms of FcgammaRII were
      able to restore antibody enhanced presentation in IIA1.6 cells but only if the
      cytoplasmic tails were intact. These results show that the B cell isoform of
      FcgammaRII (FcgammaRIIB1) can mediate capture and presentation of some
      antigen/antibody complexes and might play a role in BCR-independent antigen
      presentation in vivo.

PMID- 11828372
TI  - Leptin deficiency, not obesity, protects mice from Con A-induced hepatitis.
AB  - Leptin-deficient ob/ob mice are protected from Con A-induced hepatitis. However,
      it is unclear whether leptin deficiency or obesity itself is responsible for this
      protection. To address this question, wild-type (WT) obese mice with high serum
      leptin levels were generated by injection of gold thioglucose (WT GTG). Both Con
      A-injected WT and WT GTG mice developed hepatitis, whereas no hepatic damage was
      observed in ob/ob mice. Moreover, TNF-alpha and IFN-gamma levels as well as
      expression of the activation marker CD69 were elevated in liver mononuclear cells
      of WT and WT GTG mice, but not in ob/ob mice following administration of Con A.
      The liver of WT and WT GTG mice had the same percentage of NK T cells, a
      lymphocyte population involved in Con A-induced hepatitis. This population
      decreased equally in both WT and WT GTG mice after Con A injection. In contrast,
      the liver of ob/ob mice contained 50% less NK T cells compared to WT and WT GTG
      mice. Furthermore, no decrease in NK T cells was observed in Con A-injected ob/ob
      mice. We conclude that leptin-deficiency, not obesity, is responsible for
      protection from Con A-induced hepatitis.

PMID- 11828371
TI  - Cytokine induction by purified lipoteichoic acids from various bacterial species-
      role of LBP, sCD14, CD14 and failure to induce IL-12 and subsequent IFN-gamma
      release.
AB  - We have recently shown that highly purified lipoteichoic acid (LTA) represents a
      major immunostimulatory principle of Staphylococcus aureus. In order to test
      whether this translates to other bacterial species, we extracted and purified LTA
      from 12 laboratory-grown species. All LTA induced the release of TNF-alpha, IL
      1beta, IL-6 and IL-10 in human whole blood. Soluble CD14 (sCD14) inhibited
      monokine induction by LTA but failed to confer LTA responsiveness for IL-6 and IL
      8 release of human umbilical vein endothelial cells (HUVEC). In a competitive LPS
      binding protein (LBP) binding assay, the IC(50) of the tested LTA preparations
      was up to 3,230-fold higher than for LPS. LBP enhanced TNF-alpha release of human
      peripheral blood mononuclear cells (PBMC) upon LPS but not LTA stimulation. These
      data demonstrate a differential role for the serum proteins LBP and sCD14 in the
      recognition of LPS and LTA. Different efficacies of various anti-CD14 antibodies
      against LPS vs. LTA-induced cytokine release suggest that the recognition sites
      of CD14 for LPS and LTA are distinct with a partial overlap. While the maximal
      achievable monokine release in response to LTA was comparable to LPS, all LTA
      induced significantly less IL-12 and IFN-gamma. IL-12 substitution increased LTA
      inducible IFN-gamma release up to 180-fold, suggesting a critical role of poor
      LTA-inducible IL-12 for IFN-gamma formation. Pretreatment with IFN-gamma rendered
      galactosamine-sensitized mice sensitive to challenge with LTA. In conclusion, LTA
      compared to LPS, are weak inducers of IL-12 and subsequent IFN-gamma formation
      which might explain their lower toxicity in vivo.

PMID- 11828373
TI  - Reduction of marginal zone B cells in CD22-deficient mice.
AB  - CD22 is a B cell-specific member of the immunoglobulin superfamily and binds to
      sialic acid. CD22 inhibits B cell receptor signaling. Mice deficient for CD22
      show a largely normal B cell development. Here, we have performed a detailed
      analysis of the splenic B cell population and found that the subset of marginal
      zone (MZ) B cells was selectively reduced in CD22-deficient mice. CD22-deficient
      mice showed a lack of TNP-ficoll capturing cells in the MZ and a reduced response
      to TNP-ficoll, particularly when the antigen was applied intravenously. CD22
      deficient B cells showed both enhanced motility as well as enhanced chemotaxis to
      certain chemokines. The altered chemokine responsiveness or the higher signaling
      capacity of CD22-deficient B cells may lead to the compromised MZ B cell
      compartment, as both processes have previously been shown to affect MZ
      composition.

PMID- 11828374
TI  - Tyrosine 315 determines optimal recruitment of ZAP-70 to the T cell antigen
      receptor.
AB  - Recruitment of ZAP-70 protein tyrosine kinase to the T cell antigen receptor
      (TCR) is mediated by the binding of the SH2 domains of this enzyme to
      phosphorylated ITAM motifs in the CD3 and TCRzeta subunits. We have previously
      shown that the efficiency of both positive and negative thymocyte selection was
      decreased in knock-in mice expressing ZAP-70 mutated at Tyr315 (ZAP-70-Y315F), a
      residue laying in the interdomain B of this protein. Surprisingly, in these cells
      the amount of phosphorylated TCRzeta chain co-precipitating with ZAP-70-Y315F was
      significantly reduced compared to control mice. We report now that the binding
      affinity of ZAP-70-Y315F to phosphorylated ITAM is reduced as compared to the
      wild-type protein, whereas the intrinsic catalytic activity is untouched.
      Consequently, phosphorylated ITAM appear to be more accessible to protein
      tyrosine phosphatases (PTP) and can be readily dephosphorylated. We provide
      evidence suggesting that the defective ITAM binding induced by Tyr315 mutation is
      independent of the putative role of this residue as a binding site for Vav-1.
      Finally, we found that the extracellular signal-regulated kinase pathway is
      impaired in ZAP-70-Y315F-expressing mice. Collectively, these results demonstrate
      that Tyr315 has an unsuspected structural role in ZAP-70 and may allosterically
      regulate the function of the nearby SH2 domains.

PMID- 11828375
TI  - Evolution of IgM, IgE and IgG(1-4 )antibody responses in early childhood
      monitored with recombinant allergen components: implications for class switch
      mechanisms.
AB  - The formation of IgE antibodies against environmental allergens represents the
      hallmark of type I allergy. Data from in vitro cultured cells and experimental
      animal models provide controversial evidence for isotype switching from IgM to
      IgE production via sequential as well as non-sequential (i.e. direct) class
      switch. We analyzed the evolution of IgE responses in 11 children developing
      birch pollen and/or grass pollen allergy during the first 7 years of life using
      purified recombinant allergen molecules (major birch pollen allergen, Bet v 1;
      major timothy grass pollen allergens, Phl p 1, Phl p 2, Phl p 5). Demographic,
      clinical and serological data indicated a postnatal sensitization to pollen
      allergens. A parallel development of IgG(1-4) and IgE responses to recombinant
      allergen molecules compatible with a strictly sequential class switch to IgE was
      observed only in one child. The only partly synchronized and dissociated
      development of allergen-specific antibody responses found in all other cases can
      be best explained by a partly sequential class switch involving few switch
      stations or, more likely, by direct class switching. Kinetics and courses of
      allergen-specific antibody responses (IgM, IgG(1-4), IgE) during the first years
      of life suggest that, once established, allergen-specific IgE responses are
      driven by antigen contact rather than by cytokines controlling class switch to
      IgE.

PMID- 11828380
TI  - The Japan Society of Gene Therapy (JSGT) joins forces with other Gene Therapy
      Societies.

PMID- 11828376
TI  - Blockade of CTLA-4 enhances allergic sensitization and eosinophilic airway
      inflammation in genetically predisposed mice.
AB  - CTLA-4 (CD152) expression is restricted to subsets of activated T lymphocytes and
      shares homology with CD28. CTLA-4 and CD28 molecules both bind to B7 molecules on
      antigen-presenting cells. Whereas CD28-B7 interaction enhances T cell activation,
      cytokine production and survival, CTLA-4 signaling down-regulates T cell
      responses. Here, we studied the involvement of CTLA-4 triggering in the
      pathogenesis of allergen-induced airway inflammation in mice. Anti-CTLA-4 mAb
      were injected during i.p. sensitization with ovalbumin (OVA). This treatment
      favored OVA-specific IgE production and augmented blood eosinophilia in BALB/c
      mice. In BALB/c mice, enhanced Th2 sensitization after anti-CTLA-4 mAb injections
      resulted in more severe airway inflammation, and increased airway
      hyperresponsiveness to metacholine, bronchial eosinophilia and IL-4 and IL-5
      levels in broncho-alveolar lavage (BAL) fluid following repeated allergen
      inhalations. Importantly, aggravation of airway inflammation and enhancement of
      Th2 responses were accompanied by a significant reduction of pulmonary TGF-beta
      levels at protein level in BAL fluid as well as on mRNA level in inflamed lung
      tissue. In contrast to BALB/c mice, blockade of CTLA-4 did not alter IgE
      production nor the phenotype of airway inflammation or TGF-beta production in
      C57BL/6 mice. Our data suggest that CTLA-4 triggering represents an important
      regulatory mechanism for Th2 sensitization in genetically predisposed mice by
      modulating TGF-beta production.

PMID- 11828381
TI  - Australasian Gene Therapy Society kicks off.

PMID- 11828382
TI  - Strategies for engineering human chromosomes with therapeutic potential.
AB  - Human engineered chromosomes (HECs) have several potential advantages over
      currently used vectors for gene therapy applications. Firstly, there is no upper
      size limit to DNA that can be cloned in these vectors. Secondly, their
      extrachromosomal nature ensures that introduced genes are neither disruptive to,
      nor affected by, the genome of the host cell. Finally, being solely human in
      origin, HEC vectors should not evoke adverse host immunogenic responses. Recent
      advances have produced a variety of HECs via several different approaches. This
      review focuses on the current methodologies for making HEC vectors, the
      advantages and problems associated with each strategy, and discusses the outlook
      for HEC vectors as ex vivo therapeutic agents.

PMID- 11828383
TI  - Exposure to exogenous DNA can modify the sensitivity of the Fas apoptotic
      pathway.
AB  - BACKGROUND: Gene-transfer techniques are commonly employed for both in vitro and
      in vivo studies. However, modifications of the target cell following the
      introduction of the gene of interest are not often examined. These modifications
      can alter the immunogenicity and/or the susceptibility of the target cell to
      apoptosis and may produce unwanted consequences in vivo. METHODS: Gene transfer
      into the murine fibroblastic Psi-CRIP packaging cell line was performed using
      calcium phosphate precipitation, cationic liposome-DNA complexes or a retroviral
      RNA-mediated method. After gene transfer, Fas expression, cytokine production,
      and sensitivity to Fas ligand (FasL)-mediated death were assessed. RESULTS:
      Following transfection of a FasL expression vector by calcium phosphate
      precipitation, an unexpected increase was observed in apoptotic cell death in
      previously Fas-resistant Psi-CRIP cells. This apoptosis was due to Fas
      upregulation and an increase of sensitivity to FasL-mediated death. Other
      plasmids coding non-cytotoxic factors also modulated this apoptotic pathway. The
      co-stimulatory molecule CD80 was also upregulated. Exposure to naked DNA alone
      elicited the same response. The effect was not dependent on the methylation
      status of exogenous DNA, but was found to be dependent on the target cell type
      and might be avoided by the use of an RNA-mediated retroviral system.
      CONCLUSIONS: Plasmid transfection or simple exposure to naked DNA can increase
      sensitivity to apoptosis. The generation of FasL packaging cell lines is
      therefore limited by an increase in FasL/Fas-mediated apoptosis. These findings
      should be considered when using genetically modified transplantable cells in
      order to prevent elimination by host cytotoxic cells and in particular when cells
      are engineered using FasL.

PMID- 11828384
TI  - Plasmid DNA: is there a Toll on the way to apoptosis?

PMID- 11828385
TI  - Single-step, multiple retroviral transduction of human T cells.
AB  - BACKGROUND: Retroviral transduction of human peripheral blood T cells has
      considerable potential in the development of gene therapy strategies for
      immunological disorders. New vectors and experimental procedures have been
      developed for efficient transduction of several genes into human T cells.
      METHODS: Bicistronic retroviral vectors encoding distinct cell markers were used
      for the simultaneous multiple transduction of a human T-cell line (MT-2), as well
      as of human peripheral blood T cells from normal donors. Transduction
      efficiencies were evaluated by flow cytometry and double- and triple-transduced
      cells were isolated by fluorescence cell sorting. RESULTS: Four new bicistronic
      retroviral vectors were developed that express different gene markers under the
      control of the internal ribosome entry site (IRES) of the encephalomyocarditis
      virus. These markers are, respectively, enhanced green fluorescent protein
      (EGFP), beta-galactosidase, and truncated versions of human nerve growth factor
      receptor (Delta NGFR) and human growth hormone receptor (Delta GHR). A single 1 h
      spinoculation infection, performed in the presence of polybrene and using
      transiently produced amphotropic retroviral particles, was sufficient to obtain
      transduction efficiencies consistently greater than 50% on human peripheral blood
      T lymphocytes which had been previously stimulated for 3 days with immobilized
      anti-CD3. The transient production of viral particles encoding EGFP, Delta NGFR,
      and Delta GHR markers in the same viral supernatant has allowed up to three
      different genes to be introduced simultaneously into human T cells. CONCLUSIONS:
      This study describes new experimental conditions for efficient single-step
      multiple transduction of human primary T lymphocytes. The procedure could be of
      interest for the development of gene therapy approaches.

PMID- 11828386
TI  - Use of a lentiviral flap vector for induction of CTL immunity against melanoma.
      Perspectives for immunotherapy.
AB  - BACKGROUND: A central triple-stranded DNA structure created during HIV-1 reverse
      transcription, the central flap, acts as a cis-active nuclear import determinant
      of the HIV-1 DNA genome. Insertion of the sequences responsible for formation of
      the central DNA flap into an HIV-1-derived vector strongly enhances its
      transduction efficiency. METHODS: HIV-1 vectors with or without inclusion of the
      DNA flap and encoding the same melanoma polyepitope were constructed to transduce
      dendritic cells (DCs) and to evaluate their capacity for induction of melanoma
      specific cytotoxic T-lymphocyte (CTL) responses ex vivo and in vivo. RESULTS: HIV
      1 vectors including the DNA flap transduced up to 100% of immature mouse and
      human DCs. Inoculation of HLA-A2.1 transgenic mice with this flap vector elicited
      vigorous and multi-specific long-term anti-melanoma CTL responses, whereas the
      parental vector lacking the flap sequence was less efficient. Furthermore, human
      DCs transduced ex vivo with the recombinant DNA flap vector displayed efficient
      multi-specific primary human CTL responses against melanoma. CONCLUSION:
      Lentiviral vectors including the DNA flap should be powerful tools both for
      active immunization and for the ex vivo priming of CTL for tumor immunotherapy.

PMID- 11828387
TI  - Sustained delivery of therapeutic concentrations of human clotting factor IX--a
      comparison of adenoviral and AAV vectors administered in utero.
AB  - BACKGROUND: Prenatal somatic gene therapy has been considered for genetic
      disorders presenting with morbidity at birth. Haemophilia is associated with an
      increased risk of catastrophic perinatal bleeding complications such as
      intracranial haemorrhage, which could be prevented by gene transfer in utero.
      Prenatal gene therapy may be more promising than postnatal treatment, as the
      fetus may be more amenable to uptake and integration of therapeutic DNA and the
      immaturity of its immune system may permit life-long immune tolerance of the
      transgenic protein, thus avoiding the dominant problem in haemophilia treatment,
      the formation of inhibitory antibodies. METHODS: Adenovirus serotype 5-derived or
      AAV serotype 2-derived vectors carrying human clotting factor IX (hfIX) cDNA or a
      reporter gene were administered intramuscularly, intraperitoneally or
      intravascularly to late-gestation mouse fetuses. Both vector types were evaluated
      with respect to the kinetics of hfIX delivery to the systemic circulation and
      possible immune responses against the vector or the transgene product. RESULTS:
      Mice treated in utero by intramuscular injection of an adenoviral vector carrying
      hfIX cDNA exhibited high-level gene expression at birth and therapeutic--albeit
      continuously decreasing--plasma concentrations of hfIX over the entire 6 months
      of the study. Adenoviral vector spread to multiple organs was detected by
      polymerase chain reaction (PCR). Intramuscular, intraperitoneal or intravascular
      application of AAV vectors carrying hfIX cDNA led to much lower plasma
      concentrations of hfIX shortly after birth, which appeared to decline during the
      first month of life but stabilized in some of the mice at detectable levels. No
      signs of immune responses were found, either against the different viral vectors
      or against hfIX. CONCLUSION: This study demonstrates for the first time that
      sustained systemic delivery of a therapeutic protein can be achieved by prenatal
      gene transfer. It thus shows the feasibility of gene therapy in utero and
      provides a basis for considering this concept as a preventive therapeutic
      strategy for haemophilia and perhaps also for other plasma protein deficiencies.

PMID- 11828388
TI  - N-acetylcysteine augments adenovirus-mediated gene expression in human
      endothelial cells by enhancing transgene transcription and virus entry.
AB  - BACKGROUND: It has previously been shown that oxidants reduce the efficiency of
      adenoviral transduction in human umbilical vein endothelial cells (HUVECs). In
      this study, the effect of the antioxidant N-acetylcysteine (NAC) in adenovirus
      mediated gene transfer has been investigated. METHODS: HUVECs were pretreated or
      not with NAC, and infected with E1E3-deleted adenovirus (Ad) containing the LacZ
      gene expressed from the RSV-LTR promoter/enhancer in the presence and absence of
      NAC. Transgene expression was assessed at the protein level (histochemical
      staining, measurement of beta-Gal activity, and western blot), mRNA level (real
      time RT-PCR) and gene level (nuclear run on) 24 h and 48 h after infection.
      Adenoviral DNA was quantitated by real-time PCR, and cell surface expression of
      Coxsackie/adenovirus receptors (CAR) was determined by FACS analysis. RESULTS:
      Pretreatment of cells with NAC prior to Ad infection enhanced beta-Gal activity
      by two-fold due to an increase in viral DNA, which was related to increased CAR
      expression. When NAC was present only during the post-infection period, a five
      fold increase in beta-Gal activity and LacZ gene transcriptional activity was
      observed. When NAC was present during both the pretreatment and the post
      infection period, beta-Gal activity was further enhanced, by 15-fold.
      Augmentation of beta-Gal activity was paralleled by an increase in beta-Gal
      protein and mRNA levels. NAC did not affect the half-life of LacZ mRNA.
      CONCLUSION: Pretreatment with NAC prior to Ad infection enhances virus entry,
      while treatment with NAC post-infection increases transgene transcription. This
      strategy permits the use of lower adenoviral loads and thus might be helpful for
      gene therapy of vascular diseases.

PMID- 11828389
TI  - Jet nebulization of PEI/DNA polyplexes: physical stability and in vitro gene
      delivery efficiency.
AB  - BACKGROUND: Aerosol drug delivery currently represents the most acceptable and
      convenient delivery system for repeated drug application to the lungs. Although
      polyethyleneimine (PEI) has recently been demonstrated to mediate gene transfer
      successfully to mouse lungs via aerosol delivery, the effect of the jet
      nebulization process on the properties of PEI/DNA polyplexes has not yet been
      examined. METHODS: PEI/DNA polyplexes were generated in several commonly used
      solvents, such as distilled water, HEPES buffered saline (HBS), and 5% glucose.
      The complex parameters, such as particle size, zeta potential, DNA integrity, and
      transfection efficiency, were examined before and after jet nebulization.
      RESULTS: The complex parameters and the transfection efficiency were influenced
      by the solvent that was used for complex formulation and by the nebulization
      process itself. When polyplexes were formulated in HBS, the particle size, zeta
      potential, and DNA concentration were affected by the nebulization process and
      the transfection efficiency decreased dramatically. Polyplexes formulated in 5%
      glucose were less susceptible to the nebulization process, as indicated by only
      minor changes of the zeta potential and particle size when compared with HBS. The
      resulting transfecion efficiency was very low both before and after nebulization.
      Polyplexes formulated in distilled water had the most resistant behavior with the
      nebulization process. Zeta potential, particle size, and DNA integrity were
      influenced least of all by nebulization. CONCLUSION: As a result, the
      transfection efficiency of PEI/DNA complexes remained constant throughout the
      nebulization process only when formulated in distilled water. These data suggest
      that distilled water represents the most appropriate solvent for polyplex
      formulation when delivered by jet nebulization.

PMID- 11828390
TI  - Adenovirus or HA-2 fusogenic peptide-assisted lipofection increases cytoplasmic
      levels of plasmid in nondividing endothelium with little enhancement of transgene
      expression.
AB  - BACKGROUND: Adenovirus-assisted lipofection has been reported to increase
      transfection efficiency through mechanisms potentially involving endosome escape
      and/or nuclear targeting activity. Similarly, transfection with the viral
      fusogenic peptide HA-2 of the influenza virus hemagglutinin can increase
      transfection efficiency. However, there are few studies examining the mechanism
      and intracellular trafficking of these viral and/or viral fusogenic peptide
      assisted lipofections. METHODS AND RESULTS: Endosome escape was directly assayed
      with T7 RNA polymerase bound to plasmid (pTM beta gal) expressing beta
      galactosidase under a T7 promoter to detect transcribable plasmid that escapes
      the endosomal compartment. Lipofection of pTM beta gal with replication-deficient
      adenovirus (Ad5-null) at a multiplicity of infection (MOI) of 100 and 1000
      increased cytoplasmic levels of transcribable plasmid by 24- and 117-fold,
      respectively, over lipofection alone, without an effect on total plasmid uptake.
      However, lipofection of pCMV beta gal with Ad5-null at a MOI of 100 and 1000
      increased transgene expression only seven- and eight-fold, respectively, over
      lipofection alone. Thus, a 24-fold increase in endosome escape saturated
      expression from pCMV beta gal and provided only a seven-fold benefit in
      nondividing cells, which was not significantly increased with further increases
      in endosome escape. A cationic form of HA-2 (HA-K(4)) also caused significant
      enhancements in endosome escape, as detected with the cytoplasmic transcription
      assay. However, HA-K(4) enhancement of endosome escape did not correlate with
      transgene expression from pCMV beta gal, consistent with the detection of HA-K(4)
      mediated partitioning of plasmid to the insoluble fraction of the cell lysate.
      CONCLUSION: These results indicate that enhancement of endosome escape in
      nondividing cells does not fully alleviate rate limits related to nuclear import
      of the plasmid.

PMID- 11828391
TI  - Side-effects of a systemic injection of linear polyethylenimine-DNA complexes.
AB  - BACKGROUND: Systemic administration of linear polyethylenimine-DNA complexes (L
      PEI/DNA) results in transient expression of the transgene in the lung. This study
      analyzes the side-effects associated with L-PEI-mediated transfection. METHODS:
      Mice weighing from 16 to 25 g received increasing amounts of L-PEI/DNA
      intravenously. Gene expression was evaluated using luciferase as a reporter gene.
      Toxicity was evaluated by monitoring the appearance of shock after injection, the
      survival of the animals, and the microscopic damage in the tissues. Adherence of
      blood cells and endothelium activation were observed after CD11-b and von
      Willebrand immunostaining. Anti-aggregant treatments were used in order to
      prevent the formation of thrombi. RESULTS: Increasing the quantity of L-PEI/DNA
      resulted in a marked augmentation of the luciferase activity in the lung, but was
      associated with liver necrosis and death. Lethality was reached at lower doses in
      older mice, suggesting an age influence. Transfection was associated with
      activation of the lung endothelium and increased adhesion of small aggregates
      containing platelets and CD11-b-positive cells, without the appearance of large
      thrombi and of lung injury. Anti-aggregant treatments (aspirin, EDTA, heparin or
      clopidogrel) decreased the L-PEI-mediated transfection, supporting the hypothesis
      that platelets participate in the blocking of DNA complexes in the lung
      capillaries. CONCLUSION: This study demonstrates that L-PEI/DNA activates the
      lung endothelium and forms small aggregates, a side-effect linked to the
      transfection efficiency.

PMID- 11828393
TI  - The Journal of Gene Medicine 2001 Young Investigator Award.

PMID- 11828392
TI  - High-level gene transfer to the cornea using electroporation.
AB  - BACKGROUND: Methods for gene transfer to the cornea that yield high-level
      expression without inflammation or trauma are currently lacking. Because
      electroporation has proven effective for gene transfer in other tissues in terms
      of expression levels and safety, this study quantitatively evaluated its use in
      the cornea. METHODS: To evaluate the use of electroporation in the mouse cornea,
      plasmids expressing either luciferase or green fluorescent protein were injected
      intracorneally or subconjunctivally and square-wave electric pulses were
      immediately applied to the eyes. Gene expression was quantified at later times
      and trauma and inflammation were monitored visually and by measuring interleukin
      6 (IL-6) production. RESULTS: The application of electric pulses to eyes injected
      with plasmid resulted in nanogram levels of gene product expression. At an
      optimal field strength of 200 V/cm, no trauma, corneal edema or inflammation was
      observed. However, at higher field strengths, corneal damage was detected.
      Compared with injection of DNA alone, up to 1000-fold more gene product was
      produced using electroporation. Expression was detected as early as 6 h post
      electroporation, remained high for 3 days, and decreased by 7 days. Gene
      expression was detected over the entire surface of the cornea in both epithelial
      and stromal layers. CONCLUSIONS: These results demonstrate that electroporation
      is an excellent method for delivering genes to multiple cell layers within the
      mouse cornea and that it results in extremely high levels of gene expression with
      little, if any, inflammatory response or tissue damage, making this a very useful
      technique for corneal gene transfer.

PMID- 11828395
TI  - Affinity, specificity, diversity: a challenge for the ABC transporter TAP in
      cellular immunity.
AB  - The immune system is a perfect piece of machinery that serves only one purpose:
      to protect and defend our organism. The fact that we are still alive, although
      surrounded by a hostile environment, demonstrates impressively how well the
      immune system performs this task. Over the past decades our knowledge about the
      functions and components of the immune system has increased exponentially.
      Especially for the humoral immune system and its key players, the antibodies, a
      detailed knowledge about structure and function as well as regulation and
      communication between the individual components exists. In case of the cellular
      immune system that knowledge is not as profound as for the humoral counterpart.
      In this article we do not intend to give a complete overview about both branches
      of the immune system. Rather, we want to focus on an essential protein of the
      cellular immune system, the transporter associated with antigen processing (TAP).
      This transmembrane protein complex displays unique properties with respect to
      recognition and translocation of a vast spectrum of antigenic peptides. Its
      important role within the major histocompatibility complex (MHC) class I mediated
      immune response has been utilized by some viruses which target TAP to hide and
      escape from a deadly attack by the immune system. Here we summarize the existing
      data and analyze structural and mechanistic aspects of recognition and transport
      by which this transporter performs its task.

PMID- 11828396
TI  - Binding of insulin to its receptor: towards an understanding in three dimensions.

PMID- 11828397
TI  - In situ generation and screening of a dynamic combinatorial carbohydrate library
      against concanavalin A.
AB  - Dynamic combinatorial chemistry (DCC) is a recently introduced approach that is
      based on the generation of combinatorial libraries by reversible interconversion
      of the library constituents. In this study, the implementation of such libraries
      on carbohydrate-lectin interactions was examined. The dynamic carbohydrate
      libraries were generated from a small set (four or six compounds) of initial
      carbohydrate dimers through mild disulfide interchange, and selection was
      performed under two conditions defining either adaptive or pre-equilibrated
      libraries. Upon initiation, libraries were formed that contained comparable
      amounts of 10 or 21 individual dimeric species, dynamically interchanging during
      the scrambling process. They were probed with respect to binding to the plant
      lectin concanavalin A, either present during library generation or added after
      equilibration. The libraries could be generated easily both in the presence and
      absence of the receptor, and a bis-mannose structure was preferentially bound and
      selected from the mixture. Scrambling of the library in the presence of the
      receptor resulted in slightly higher yields than when the receptor was added
      after scrambling, indicating that the receptor to some extent acts as a
      thermodynamic trap during library generation. The present results illustrate the
      extention of the DCC approach to carbohydrate recognition groups, the generation
      of isoenergetic dynamic libraries, and the implementation of either adaptive or
      pre-equilibrated procedures.

PMID- 11828398
TI  - Protein folding transition states: elicitation of Hammond effects by 2,2,2
      trifluoroethanol.
AB  - Adaptation of the techniques of classical physical-organic chemistry to the study
      of protein folding has led to our current detailed understanding of the
      transition states. Here, we have applied a series of structure--activity
      relationships to analyse the effects on protein folding transition states of
      2,2,2-trifluoroethanol (TFE), a reagent that is usually assumed to act by
      stabilising secondary structure. The folding and unfolding of the highly alpha
      helical tetramerisation domain of p53 provides a useful paradigm for analysing
      its effects on kinetics: The first step of its folding consists of an association
      reaction with little, if any, formation of secondary structure in the transition
      state; and the final step of the folding reaction involves just the formation of
      bonds at subunit interfaces, with the alpha-helical structure being completely
      formed. We have systematically measured the effects of TFE on two sets of
      structure--activity relationships. The first is for Phi values, which measure the
      degree of non-covalent bond formation at nearly every position in the transition
      state. The second is for relative effects of the denaturant, guanidinium
      chloride, on kinetics and equilibria, which measure the gross position of the
      transition state on the reaction co-ordinate. We find that TFE modulated the
      kinetics by a variety of effects other than that on secondary structure. In
      particular, there were Hammond effects, movement of the position of the
      transition state along the reaction co-ordinate, which either significantly
      speeded up or slowed down protein unfolding, depending on the particular mutant
      examined. The gross effects of TFE on protein folding kinetics are thus not a
      reliable guide to the structures of transition states.

PMID- 11828399
TI  - Pheromonal and kairomonal activities can be separated: synthesis and bioactivity
      studies of pine bast scale sex pheromones and their analogues.
AB  - New syntheses were achieved to secure matsuone (1), the pheromone of the pine
      scale Matsucoccus matsumurae, that of M. feytaudi (2), and that of M. josephi
      (3). Five analogues (4-8) of 1, 2, and 3 were synthesized and their bioactivities
      studied. The pheromone analogue 7 showed relatively strong pheromonal activity
      toward M. josephi, while it was inactive as a kairomone toward the predator
      Elatophilus hebraicus. Similarly, analogue 8 acted as a pheromone for M.
      feytaudi, but it did not attract any of its local predators. The M. feytaudi
      pheromone 2 exhibited strong kairomonal activity toward E. hebraicus, but was not
      active as a pheromone mimic to attract M. josephi.

PMID- 11828400
TI  - Synthesis and biological evaluation of aza-epothilones.

PMID- 11828401
TI  - Toward the synthesis of large oligosaccharide-based dendrimers.

PMID- 11828402
TI  - Protein targeting (Nobel lecture).

PMID- 11828403
TI  - The multiplasmid approach: a new perspective for combinatorial biosynthesis.

PMID- 11828404
TI  - Surface coating with cyclic RGD peptides stimulates osteoblast adhesion and
      proliferation as well as bone formation.
AB  - The physiological inertness of synthetic implant materials often results in
      insufficient implant integration and limited acceptance of implants in tissues.
      After implantation the implant surface is often separated from the surrounding
      healthy and regenerating tissue, for example by a fibrous capsule. To avoid this
      host-versus-graft reaction, a strong mechanical contact between tissue and
      implant must be ensured. An enhanced contact between graft and the surrounding
      tissue can be provided by coating the implant with cell-adhesive molecules. The
      highly active and alpha(v)beta(3)- and alpha(v)beta(5)-integrin-selective peptide
      c(-RGDfK-) (f=D-phenylalanine) was functionalized with various linker molecules
      containing an acrylamide end group by using the lysine side chain of c(-RGDfK-).
      The acrylamide group can be used to bind the peptide covalently to poly(methyl
      methacrylate) (PMMA) surfaces. The coated surfaces effectively bind to murine
      osteoblasts as well as human osteoblasts in vitro when a minimum distance of 3.5
      nm between surface and the constrained RGD sequence is provided. In contrast to
      osteoblasts in cell suspension, surface-bound osteoblasts show no apoptosis but
      proliferate by a factor of 10 over a 22 d period. Coating of inert implant
      surfaces with highly active and alpha(v)-selective peptides affords a marked
      improvement in osteoblast binding over current technologies. In vivo studies show
      that peptide-coated PMMA pellets implanted into the patella groove of rabbits are
      integrated into the regenerating bone tissue faster and more strongly than
      uncoated pellets.

PMID- 11828405
TI  - The substrate specificity of a recombinant cysteine protease from Leishmania
      mexicana: application of a combinatorial peptide library approach.
AB  - The substrate specificity of CPB2.8DeltaCTE, a recombinant cysteine protease from
      Leishmania mexicana, was mapped by screening a fluorescence-quenched
      combinatorial peptide library. Results from library screening indicated a
      preference for Arg or Lys in the S(3) subsite and for hydrophobic residues, both
      aliphatic and aromatic, in S(2). The S(1) subsite exhibited a specificity for the
      basic residues Arg and Lys. Generally, the specificity of the primed subsites was
      less strict compared with the non-primed side which showed preference for Arg,
      Lys and Ala in S'(1), Arg, Pro and Gly in S'(2) and Lys, Arg and Ser in S'(4). By
      contrast, a strict preference for the basic residues Arg and Lys was found for
      S'(3). Overall, there was a trend for basic residues in alternating subsites and
      smaller residues in the primed sites compared with the non-primed sites. In
      addition, there were strict requirements for the amino acids in subsites S(3)-
      S(1). Fluorescence-quenched peptides from the library with the highest on-resin
      cleavage were resynthesised and their kinetics of hydrolysis by CPB2.8DeltaCTE
      assessed in solution phase assays. Several good substrates containing the
      quintessential dipeptide particular to cathepsin-L-like enzymes, -F-R/K-, in P(2)
      and P(1) were identified (e.g. Y(NO(2))-EKFR down arrow RGK-K(Abz)G, Abz=2
      aminobenzoyl; k(cat)K(m)(-1)=4298 mM(-1)s(-1)). However, novel substrates
      containing the dipeptide -L/I-Q- in P(2) and P(1) were also well hydrolysed (e.g.
      Y(NO(2))-YLQ down arrow GIQK-K(Abz)G; k(cat)K(m)(-1)=2583 mM(-1)s(-1)). The
      effect of utilising different fluorescent donor--quencher pairs on the value of
      k(cat)K(m)(-1) was examined. Generally, the use of the Abz/Q-EDDnp donor-
      quencher pair (EDDnp=N-(2,4-dinitrophenyl)ethylenediamine) instead of
      K(Abz)/Y(NO(2)) resulted in higher k(cat)K(m)(-1) values for analogous
      substrates.

PMID- 11828406
TI  - Transmembrane B-DNA.

PMID- 11828407
TI  - Semisynthesis of Ht31(493--515): involvement of PKA-anchoring proteins in the
      regulation of the cAMP-dependent chloride current in heart cells.

PMID- 11828408
TI  - Linking the fields--the interplay of organic synthesis, biophysical chemistry,
      and cell biology in the chemical biology of protein lipidation.
AB  - Research in the biological sciences has undergone a fundamental and dramatic
      change during the last decades. Whereas biology was more phenomenologically
      oriented for a long time, today many biological processes are investigated and
      understood in molecular detail. It has become evident that all biological
      phenomena have a chemical basis: Biology is based on chemical principles. In the
      past, this insight had led to the development of biochemistry, molecular biology,
      and modern pharmacology. Today it increasingly determines the manner in which
      various biological phenomena are studied. The tools provided by classical
      biological techniques often are not sufficient to address the prevailing issues
      in precise molecular detail. Instead, the strengths of both chemical and
      biological methodology have to be used. Several recent research projects have
      proven that combining the power of organic synthesis with cell biology may open
      up entirely new and alternative opportunities for the study of biological
      problems. In this review we summarize the successful interplay between three
      disciplines-organic synthesis, biophysics, and cell biology-in the study of
      protein lipidation and its relevance to targeting of proteins to the plasma
      membrane of cells in precise molecular detail. This interplay is highlighted by
      using the Ras protein as a representative example. The development of methods for
      the synthesis of Ras-derived peptides and fully functional Ras proteins, the
      determination of their biophysical properties, in particular the ability to bind
      to model membranes, and finally the use of synthetic Ras peptides and Ras
      proteins in cell biological experiments are addressed. The successful combination
      of these three disciplines has led to a better understanding of the factors
      governing the selective targeting of Ras and related lipid-modified proteins to
      the plasma membrane.

PMID- 11828409
TI  - The chemistry and biology of discodermolide.

PMID- 11828410
TI  - Direct NMR-spectroscopic determination of active-enzyme concentration by
      titration with a labeled inhibitor: determination of the k(cat) value of almond
      beta-glucosidase.
AB  - A new method for the determination of active-enzyme concentration of a
      glucosidase by using (13)C NMR spectroscopy is reported. The method consists of
      quantifying the binding between a (13)C-labelled, strong competitive inhibitor,
      [5-(13)C]-1-azafagomine (1), and the enzyme. The concentration of free inhibitor
      1 is measured in a series of binding experiments from the intensity of its NMR
      signal relative to that of a reference. From a plot of the concentrations of
      bound vs. free inhibitor 1, the amount of specifically bound 1, that is, the
      amount of active sites, is determined. From this value, active-enzyme
      concentration and k(cat) value can be calculated.

PMID- 11828411
TI  - A new combined computational and NMR-spectroscopical strategy for the
      identification of additional conformational constraints of the bound ligand in an
      aprotic solvent.
AB  - This study documents the feasibility of switching to an aprotic medium in sugar
      receptor research. The solvent change offers additional insights into mechanistic
      details of receptor--carbohydrate ligand interactions. If a receptor retained
      binding capacity in an aprotic medium, solvent-exchangeable protons of the ligand
      would not undergo transfer and could act as additional sensors, thus improving
      the level of reliability in conformational analysis. To probe this possibility,
      we first focused on hevein, the smallest lectin found in nature. The NMR
      spectroscopic measurements verified complexation, albeit with progressively
      reduced affinity by more than 1.5 orders of magnitude, in mixtures of up to 50%
      dimethyl sulfoxide (DMSO). Since hevein lacks the compact beta-strand arrangement
      of other sugar receptors, such a structural motif may confer enhanced resistance
      to solvent exchange. Two settings of solid-phase activity assays proved this
      assumption for three types of alpha- and/or beta-galactoside-binding proteins,
      that is, a human immunoglobulin G (IgG) subfraction, the mistletoe lectin, and a
      member of the galectin family of animal lectins. Computer-assisted calculations
      and NMR experiments also revealed no conspicuous impact of the solvent on the
      conformational properties of the tested ligands. To define all possible nuclear
      Overhauser effect (NOE) contacts in a certain conformation and to predict
      involvement of exchangeable protons, we established a new screening protocol
      applicable during a given molecular dynamics (MD) trajectory and calculated
      population densities of distinct contacts. Experimentally, transferred NOE (tr
      NOE) experiments with IgG molecules and the disaccharide Gal'alpha1-3Galbeta1-R
      in DMSO as solvent disclosed that such an additional crosspeak, that is, Gal'OH2-
      GalOH4, was even detectable for the bound ligand under conditions in which spin
      diffusion effects are suppressed. Further measurements with the plant lectin and
      galectins confirmed line broadening of ligand signals and gave access to
      characteristic crosspeaks in the aprotic solvent and its mixtures with water. Our
      combined biochemical, computational, and NMR-spectroscopical strategy is expected
      to contribute notably to the precise elucidation of the geometry of ligands bound
      to compactly folded sugar receptors and of the role of water molecules in protein
      -ligand (carbohydrate) recognition, with relevance to areas beyond the
      glycosciences.

PMID- 11828412
TI  - Satellite hole spectroscopy of thrombin-aptamer complexes.

PMID- 11828413
TI  - Synthesis of characteristic H-Ras lipopeptides by employing noble-metal-, acid-,
      and reduction-labile blocking groups.

PMID- 11828414
TI  - Glycopeptide synthesis and the effects of glycosylation on protein structure and
      activity.
AB  - Despite the omnipresence of protein glycosylation in nature, little is known
      about how the attachment of carbohydrates affects peptide and protein activity.
      One reason is the lack of a straightforward method to access biologically
      relevant glycopeptides and glycoproteins. The isolation of homogeneous
      glycopeptides from natural sources is complicated by the heterogeneity of
      naturally occuring glycoproteins. It is chemical and chemoenzymatic synthesis
      that is meeting the challenge to solve this availability problem, thus playing a
      key role for the advancement of glycobiology. The current art of glycopeptide
      synthesis, albeit far from being routine, has reached a level of maturity that
      allows for the access to homogeneous and pure material for biological and
      medicinal research. Even the ambitious goal of the total synthesis of an entire
      glycoprotein is within reach. It is demonstrated that with the help of synthetic
      glycopeptides the effects of glycosylation on protein structure and function can
      be studied in molecular detail. For example, in immunology, synthetic (tumour
      specific) glycopeptides can be used as immunogens to elicit a tumour-cell
      specific immune response. Again, synthetic glycopeptides are an invaluable tool
      to determine the fine specificity of the immune response that can be mediated by
      both carbohydrate-specific B and T cells. Furthermore, selected examples for the
      use of synthetic glycopeptides as ligands of carbohydrate-binding proteins and as
      enzyme substrates or inhibitors are presented.

PMID- 11828415
TI  - The malaria pigment haemozoin-a focal point of action for antimalarial drugs.

PMID- 11828416
TI  - Translational termination not yet at its end.

PMID- 11828417
TI  - Shape complementarity, binding-site dynamics, and transition state stabilization:
      a theoretical study of Diels-Alder catalysis by antibody 1E9.
AB  - Antibody 1E9 is a protein catalyst for the Diels-Alder reaction between
      tetrachlorothiophene dioxide and N-ethylmaleimide. Quantum mechanical
      calculations have been employed to study the 1E9-catalyzed Diels-Alder reaction
      in the gas phase. The transition states and intermediates were all determined at
      the B3LYP/6-31G*//HF/6-31G* level. The cycloaddition step is predicted to be rate
      determining, and the endo reaction pathway is strongly favored. Binding of the
      reactants and the transition states to antibody 1E9 was investigated by docking
      and molecular dynamics simulations. The linear interaction energy (LIE) method
      was adopted to estimate the free energy barrier of the 1E9-catalyzed Diels-Alder
      reaction. The catalytic efficiency of antibody 1E9 is achieved by enthalpic
      stabilization of the transition state, near-perfect shape complementarity of the
      hydrophobic binding site for the transition state, and a strategically placed
      hydrogen-bonding interaction.

PMID- 11828418
TI  - The 6-OH group of D-inositol 1-phosphate serves as an H-bond donor in the
      catalytic hydrolysis of the phosphate ester by inositol monophosphatase.
AB  - Inositol monophosphatase plays a pivotal role in the biosynthesis of secondary
      messengers and is believed to be a target for lithium therapy. It is established
      how a lithium ion works in inhibiting the enzyme but details of the mechanism for
      the direct magnesium ion activated hydrolysis of the substrate have been elusive.
      It is known that substrates require a minimal 1,2-diol phosphate structural
      motif, which in D-myo-inositol 1-phosphate relates to the fragment comprising the
      1-phosphate ester and the 6-hydroxy group. Here it is shown that inhibitors that
      are D-myo-inositol 1-phosphate substrate analogues possessing 6-substituents
      larger than the 6-hydroxy group of the substrate, for example, the 6-O-methyl
      analogue, are able to bind to the enzyme in a congruous manner to the substrate.
      It is demonstrated, however, that such compounds show no substrate activity
      whatsoever. It is also shown that a 6-amino group is able to fulfil the role of
      the 6-hydroxy group of the substrate in conferring substrate activity and that a
      6-methylamino group is similarly able to support catalysis. The results indicate
      that a 6-substituent capable of serving as a hydrogen-bond donor is required in
      the catalytic mechanism for hydrolysis. It has recently been shown that inositol
      is displaced from phosphorus with inversion of stereochemistry and we expect that
      the nucleophilic species is associated with Mg(2+)-1. It is proposed here that
      the role of the 6-hydroxy group of the substrate is to H-bond with a water
      molecule or hydroxide ion located on Mg(2+)-2. From this analysis, it appears
      that the water molecule bound to Mg(2+)-2 serves as a proton donor for the
      inositolate leaving group in a process that stabilises the alkoxide product and
      retards the back-reaction.

PMID- 11828420
TI  - Preparation and antimalarial activities of "trioxaquines", new modular molecules
      with a trioxane skeleton linked to a 4-aminoquinoline.

PMID- 11828419
TI  - Synthesis of a C-glycoside analogue of beta-D-galactosyl hydroxynorvaline and its
      use in immunological studies.
AB  - A C-linked isostere of beta-D-galactosylated hydroxynorvaline has been prepared
      in eight steps from per-O-benzylated galactopyranolactone. Addition of a
      homoallylic Grignard reagent to the lactone, reduction of the resulting
      hemiacetal with triethylsilane, and a Wittig reaction with Garner's aldehyde were
      key steps in this synthesis. The C-linked building block was then incorporated at
      position 264 into the fragment CII(256--270) from typeII collagen by solid-phase
      synthesis using a combination of the tert-butoxycarbonyl (Boc) and 9
      fluorenylmethoxycarbonyl (Fmoc) protective group strategies. Deprotection of the
      benzylated C-linked galactosyl moiety was achieved simultaneously with cleavage
      of the glycopeptide from the solid phase by using triethylsilyl
      trifluoromethanesulfonate in TFA. Helper T-cell hybridomas obtained in a mouse
      model for rheumatoid arthritis responded to the C-linked glycopeptide when
      presented by classII MHC molecules. However, 10- to 20-fold higher concentrations
      were required as compared to when O-linked beta-D-galactosylated hydroxynorvaline
      or hydroxylysine (Hyl) were present at position 264 of CII(256--270). Thus,
      replacement of a single oxygen atom by a methylene group in the carbohydrate
      moiety of a glycopeptide antigen had a substantial influence on the T-cell
      response. This reveals that T cells are able to recognize the carbohydrate moiety
      of glycopeptide antigens with high specificity. Finally, the results suggest that
      structural modifications of beta-D-Gal-Hyl(264) in CII(256--270) may give altered
      peptide ligands that can be used for induction of tolerance in autoimmune
      rheumatoid arthritis.

PMID- 11828421
TI  - Designed prostaglandins with neurotrophic activities.

PMID- 11828422
TI  - Molecular mechanisms of death-receptor-mediated apoptosis.
AB  - Apoptosis, also called "programmed cell death", can be induced by a variety of
      stimuli including activation of death receptors by the corresponding death
      ligands. Death receptors are a subgroup of the tumor necrosis factor (TNF)/nerve
      growth factor (NGF) receptor superfamily and are characterized by a death domain,
      which is required for signal transduction. Upon apoptosis induction, caspases, a
      family of aspartyl-specific cysteine proteases, are activated, which are the main
      executioners of apoptosis. Finally, specific death substrates are cleaved,
      resulting in the morphologic features of apoptosis. Depending on the cell type,
      activation of mitochondria is of central significance for apoptosis induction.
      This signaling pathway can be modulated by different pro- and anti-apoptotic
      proteins such as Bax and Bcl-2, which are localized at the mitochondria.
      Furthermore, apoptosis initiation can be prevented at the death receptor level by
      FLICE (caspase-8)-inhibitory proteins (FLIPs). Deregulation of apoptosis is
      associated with diseases like cancer, autoimmunity, and AIDS. Therefore, the
      elucidation of cell death pathways and the identification of modulators of
      apoptosis have many therapeutic implications.

PMID- 11828423
TI  - The ribosome functions as a ribozyme.

PMID- 11828424
TI  - Discovery of a new bacterial polyketide biosynthetic pathway.

PMID- 11828425
TI  - Photocontrol of DNA duplex formation by using azobenzene-bearing
      oligonucleotides.
AB  - The duplex-forming activities of oligonucleotides can be photomodulated by
      incorporation of an azobenzene unit. Upon isomerizing the trans-azobenzene to the
      cis form by irradiation with UV light, the T(m) value of the duplex (with the
      complementary DNA) is lowered so that the duplex is dissociated. The duplex is
      formed again when the cis-azobenzene is converted to the trans-azobenzene by
      irradiation with visible light. The photoregulation is successful irrespective of
      the position of the azobenzene unit in the oligonucleotides. The trans-azobenzene
      in the oligonucleotides intercalates between two DNA base pairs in the duplexes
      and stabilizes them because of a favorable enthalpy change. The nonplanar
      structure of a cis-azobenzene is unfavorable for such an interaction. These
      photoresponsive oligonucleotides are promising candidates for the regulation of
      various bioreactions.

PMID- 11828426
TI  - Isolation and amino acid sequence of a serine proteinase inhibitor from common
      flax (Linum usitatissimum) seeds.
AB  - LUTI (Linum usitatissimum trypsin inhibitor), a member of the potato inhibitor I
      family, has been isolated from seeds of flax by ethanol fractionation, ion
      exchange chromatography on CM-Sephadex C-25, affinity purification on immobilized
      methylchymotrypsin (alpha-chymotrypsin in which His57 has been converted to 3
      methylhistidine) in the presence of 5M NaCl, and finally by reversed-phase HPLC.
      The 7655 Da inhibitor consists of a single polypeptide chain of 69 residues with
      one disulfide bridge. The molecule is acetylated at the N terminus. Its primary
      structure has been determined after limited proteolysis of the native molecule
      with trypsin at the reactive site, cleavage with cyanogen bromide or arginyl
      endopeptidase (Arg-gingipain), and alcoholytic deacetylation of the N-terminally
      blocked serine. The association constants (K(a)) of LUTI with bovine beta-trypsin
      and alpha-chymotrypsin are 3.58x10(10) M(-1) and 5.02x10(5) M(-1), respectively.
      High NaCl concentration (3M) increased the association constant of LUTI with
      alpha-chymotrypsin to 6.64x10(7) M(-1). To our knowledge, LUTI is the first
      serine-proteinase-type inhibitor isolated from a plant of the Linaceae family.

PMID- 11828427
TI  - Cell-surface recognition of biotinylated membrane proteins requires very long
      spacer arms: an example from glucose-transporter probes.
AB  - Glucose transporters (GLUTs) can be photoaffinity labelled by
      (diazirinetrifluoroethyl)benzoyl-substituted glucose derivatives and the adduct
      can be recognised, after detergent solubilisation of membranes, by using
      streptavidin-based detection systems. However, in intact cells recognition of
      photolabelled GLUTs by avidin and anti-biotin antibodies only occurs if the
      bridge between the photoreactive and the biotin moieties has a minimum of 60--70
      spacer atoms. We show that a suitably long bridge can be synthesised with a
      combination of polyethylene glycol and tartarate groups and that introduction of
      these spacers generates hydrophilic products that can be cleaved with periodate.
      Introduction of the very long spacers does not appreciably reduce the affinity of
      interaction of the probes with the transport system.

PMID- 11828428
TI  - Synthesis and biological evaluation of nonylprodigiosin and macrocyclic
      prodigiosin analogues.
AB  - Nonylprodigiosin (4) and various of its analogues have been prepared by Suzuki
      cross-coupling reactions of a well accessible pyrrolyl triflate with (hetero)aryl
      boronic acid derivatives bearing alkenyl side chains. The resulting alkenes or
      dienes were subjected to metathesis dimerization or ring-closing metathesis (RCM)
      reactions, respectively, by using a ruthenium indenylidene complex as the
      catalyst. The biological activity of the products thus obtained was tested in two
      different assays monitoring i) the proliferation of murine spleen cells induced
      by lipopolysaccharides (LPS) and concanavalin A (Con A), and ii) the vacuolar
      acidification of baby hamster kidney (BHK) cells. Compounds 4 and 21 suppressed
      Con A-induced T-cell proliferation much more potently than LPS-induced B-cell
      proliferation. Furthermore, compounds 4 and 26 markedly inhibited vacuolar
      acidification, although other compounds exhibited no or only marginal effects.
      Thus, the immunosuppressive activity of prodigiosins toward T-cell proliferation
      seems to be mediated through cellular targets distinct from vacuolar
      acidification, and the prodigiosin analogues might be powerful tools to dissect
      these biological responses. The X-ray crystal structure of the macrocyclic
      product 25 has been determined, showing that the replacement of one pyrrole ring
      of the parent compound 4 by a phenyl group does not alter the overall electronic
      features of the remaining heterocyclic ring system of these alkaloids.

PMID- 11828430
TI  - Heterogeneous assembly of complementary peptide pairs into amyloid fibrils with
      alpha-beta structural transition.

PMID- 11828429
TI  - Synthesis and biological evaluation of 12,13-cyclopropyl and 12,13-cyclobutyl
      epothilones.

PMID- 11828431
TI  - Selective cleavage of unpaired uridines with a tyrosine-cyclen conjugate.

PMID- 11828432
TI  - Chain termination steps in nonribosomal peptide synthetase assembly lines:
      directed acyl-S-enzyme breakdown in antibiotic and siderophore biosynthesis.

PMID- 11828433
TI  - Circe effect versus enzyme preorganization: what can be learned from the
      structure of the most proficient enzyme?

PMID- 11828434
TI  - Crystal structures of orotidine monophosphate decarboxylase: does the structure
      reveal the mechanism of nature's most proficient enzyme?

PMID- 11828435
TI  - DNA interstrand cross-linking efficiency and cytotoxic activity of novel
      cadmium(II)-thiocarbodiazone complexes.
AB  - We have prepared mono- and binuclear complexes of Zn(II) and Cd(II) with bis(2
      pyridyl aldehyde) thiocarbodiazone (H(2)L(1)) and bis(methyl 3-pyridyl ketone)
      thiocarbodiazone (H(2)L(2)). Cytotoxicity data against the ovarian tumor cell
      line A2780cisR (acquired resistance to cisplatin) indicate that the mononuclear
      complex Cd/H(2)L(2) (1) and the binuclear complex Cd(2)/H(2)L(1) (4) are able to
      circumvent cisplatin resistance and that their cytotoxic activity does not
      substantially vary after depletion of intracellular levels of glutathione.
      Moreover, DNA binding studies show that complexes 1 and 4 have higher efficiency
      than cisplatin at forming DNA interstrand cross-links in both naked pBR322
      plasmid and A2780cisR cellular DNA. Interestingly, the thiocarbodiazone ligands
      alone do not show the biological properties of complexes 1 and 4. Altogether
      these results suggest that DNA interstrand cross-link formation by compounds 1
      and 4 might be related with their cytotoxic activity in cisplatin-resistant
      cells. We think that compounds 1 and 4 may represent a novel structural lead for
      the development of cadmium cytotoxic agents capable of improving antitumor
      activity in cisplatin-resistant tumors.

PMID- 11828436
TI  - Fluorescence resonance energy transfer as a probe for G-quartet formation by a
      telomeric repeat.
AB  - The secondary structure of guanine-rich oligodeoxynucleotides has been
      investigated with fluorescent probes. Intramolecular folding of a telomeric
      oligonucleotide into a quadruplex led to fluorescence resonance energy transfer
      (FRET) between a donor (fluorescein) and an acceptor (tetramethylrhodamine)
      covalently attached to the 5' and 3' ends of the DNA, respectively. Depending on
      oligonucleotide length, quenching efficiency varied between 0.45 and 0.72 at 20
      degrees C. The conjugation of the dyes to the oligonucleotide had a limited, but
      significant, influence on the thermodynamics of G-quartet formation.
      Intramolecular folding was demonstrated from the concentration independence of
      fluorescence resonance energy transfer over a wide concentration range. Folding
      of the oligonucleotide was confirmed by UV absorption, UV melting, and circular
      dichroism experiments. The folding of the G-quartet could be followed at
      concentrations as low as 100 pM. Fluorescence resonance energy transfer can thus
      be used to reveal the formation of multistranded DNA structures.

PMID- 11828437
TI  - An artificial primosome: design, function, and applications.
AB  - Double-stranded (ds) DNA is capable of the sequence-specific accommodation of an
      additional oligodeoxyribonucleotide strand by the peptide nucleic acid(PNA)
      assisted formation of a so-called PD-loop. We demonstrate here that the PD-loop
      may function as an artificial primosome within linear, nonsupercoiled DNA
      duplexes. DNA polymerase with its strand displacement activity uses this
      construct to initiate the primer extension reaction at a designated dsDNA site.
      The primer is extended by several hundred nucleotides. The efficiency of dsDNA
      priming by the artificial primosome assembly is comparable to the single-stranded
      DNA priming used in various assays. The ability of the PD-loop structure to
      perform like an artificial primosome on linear dsDNA may find applications in
      biochemistry, molecular biology, and molecular biotechnology, as well as for DNA
      diagnostics. In particular, multiple labels can be incorporated into a chosen
      dsDNA site resulting in ultrasensitive direct quantification of specific
      sequences. Furthermore, nondenaturing dsDNA sequencing proceeds from the PD-loop.
      This approach opens the way to direct isothermal reading of the DNA sequence
      against a background of unrelated DNA, thereby eliminating the need for
      purification of the target DNA.

PMID- 11828438
TI  - Manumycin A and its analogues are irreversible inhibitors of neutral
      sphingomyelinase.

PMID- 11828439
TI  - Application of 3-quinolinoyl picket porphyrins to the electroreduction of
      dioxygen to water: mimicking the active site of cytochrome c oxidase.

PMID- 11828440
TI  - Antifreeze glycoproteins--preventing the growth of ice.

PMID- 11828441
TI  - Single-molecule study reveals a complex E. coli RNA polymerase.

PMID- 11828442
TI  - Peptoid - peptide hybrids that bind Syk SH2 domains involved in signal
      transduction.
AB  - Peptoid-peptide hybrids are oligomeric peptidomimetics that contain one or more N
      substituted glycine residues. In these hybrids, the side chains of one or several
      amino acids are "shifted" from the alpha-carbon atom to the amide nitrogen atom.
      A library of phosphorylated peptoid-peptide hybrids derived from the sequence
      pTyr-Glu-Thr-Leu was synthesized and tested for binding to the tandem SH2 domain
      of the protein tyrosine kinase Syk. A considerable influence of the side chain
      position was observed. Compounds 19-21, 24, and 25 comprising a peptoid NpTyr
      and/or NGlu residue did not show any binding. Compounds 22, 23, and 26 containing
      an NhThr (hThr=homothreonine) and/or NLeu peptoid residue showed binding with
      IC(50) values that were only five to eight times higher than that of the
      tetrapeptide lead compound 18. These data show that side chain shifting is
      possible with retention of binding capacity, but only at the two C-terminal
      residues of the tetramer. This method of a peptoid scan using peptoid-peptide
      hybrids appears to be very useful to explore to what extent a peptide sequence
      can be transformed into a peptoid while retaining its affinity.

PMID- 11828443
TI  - Structural changes of cytochrome c(552) from Thermus thermophilus adsorbed on
      anionic and hydrophobic surfaces probed by FTIR and 2D-FTIR spectroscopy.
AB  - The structural changes of cytochrome c(552) bound to anionic and hydrophobic clay
      surfaces have been investigated by Fourier transform infrared spectroscopy.
      Binding to the anionic surface of montmorillonite is controlled by electrostatic
      interactions since addition of electrolyte (0.5 mol L(-1) KCl) causes desorption
      of more than 2/3 of the protein molecules. Electrostatic binding occurs through
      the back side of the protein (i.e., remote from the heme site) and is associated
      only with subtle changes of the secondary structure. In contrast, adsorption to
      the hydrophobic surface of talc leads to a decrease in alpha-helical structure by
      ca. 5% and an increase in beta-sheet structure by ca. 6%. These structural
      changes are attributed to a hydrophobic region on the front surface of cytochrome
      c(552) close to the partially exposed heme edge. This part on the protein surface
      is identified as the interaction domain for talc and most likely also serves for
      binding to the natural reaction partner, a ba(3)-oxidase. Fourier transform
      infrared spectra of cytochrome c(552) and the clay-cytochrome c(552) complexes
      have been measured as a function of time following dissolution and suspension in
      deuterated buffer, respectively. A two-dimensional correlation analysis was
      applied to these spectra to investigate the dynamics of the structural changes in
      the protein. For both complexes, adsorption and subsequent unfolding processes in
      the binding domains are faster than the time resolution of the spectroscopic
      experiments. Thus, the processes that could be monitored are refolding of peptide
      segments and side chain rearrangements following the adsorption-induced
      perturbation of the protein structure and the solvation of the adsorbed protein.
      In each case, side chain alterations of solvent-exposed tyrosine, aspartate, and
      glutamate residues were observed. For the cytochrome c(552)-talc complex, these
      changes are followed by a slow refolding of the peptide chain in the binding
      domain and, subsequently, a further H/D exchange of amide group protons.

PMID- 11828444
TI  - New insights into the mechanistic details of the carbonic anhydrase cycle as
      derived from the model system [(NH(3))(3)Zn(OH)](+)/CO(2): how does the
      H(2)O/HCO(3)(-) replacement step occur?
AB  - The full reaction path for the conversion of carbon dioxide to hydrogencarbonate
      has been computed at the B3LYP/6-311+G** level, employing a [(NH(3))(3)Zn(OH)](+)
      model catalyst to mimic the active center of the enzyme. We paid special
      attention to the question of how the catalytic cycle might be closed by retrieval
      of the catalyst. The nucleophilic attack of the catalyst on CO(2) has a barrier
      of 5.7 kcal mol(-1) with inclusion of thermodynamic corrections and solvent
      effects and is probably the rate-determining step. This barrier corresponds well
      with prior experiments. The intermediate result is a Lindskog-type structure that
      prefers to stabilize itself via a rotation-like transition state to give a
      Lipscomb-type product, which is a monodentate hydrogencarbonate complex. By
      addition of a water molecule, a pentacoordinated adduct with pseudo-trigonal
      bipyramidal geometry is formed. The water molecule occupies an equatorial
      position, whereas the hydrogencarbonate ion is axial. In this complex, proton
      transfer from the Zn-bound water molecule to the hydrogencarbonate ion is
      extremely facile (barrier 0.8 kcal mol(-1)), and yields the trans,trans-conformer
      of carbonic acid rather than hydrogencarbonate as the leaving group. The carbonic
      acid molecule is bound by a short O...H-O hydrogen bond to the catalyst
      [(NH(3))(3)Zn(OH)](+), in which the OH group is already replaced by that of an
      entering water molecule. After deprotonation of the carbonic acid through a
      proton relay to histidine 64, modeled here by ammonia, hydrogencarbonate might
      undergo an ion pair return to the catalyst prior to its final dissociation from
      the complex into the surrounding medium.

PMID- 11828445
TI  - Scanning force microscopy study on a single-stranded DNA: the genome of
      parvovirus B19.
AB  - The genome of parvovirus B19 is a 5600-base-long single-stranded DNA molecule
      with peculiar sequence symmetries. Both complementary forms of this single
      stranded DNA are contained in distinct virions and they hybridize
      intermolecularly to double-stranded DNA if extracted from the capsids with
      traditional methods, thus losing some of their native structural features. A
      scanning force microscopy analysis of these double-stranded DNA molecules after
      thermal denaturation and renaturation gave us the chance to study the possible
      states that this DNA can assume in both its single-stranded and double-stranded
      forms. A novel but still poorly reproducible in situ lysis experiment that we
      have conducted on single virions with the scanning force microscope made it
      possible to image the totally unpaired state that the single-stranded DNA
      molecule most likely assumes inside the viral particle. Structural considerations
      on single molecules offer the opportunity for the formulation of plausible
      hypotheses on the interaction between the DNA and the viral structural proteins
      that could prove important for the DNA packaging in the capsid and, possibly, the
      viral infection mechanisms.

PMID- 11828447
TI  - An error-prone T7 RNA polymerase mutant generated by directed evolution.
AB  - Viruses replicate their genomes at exceptionally high mutation rates. Their
      offspring evolve rapidly and therefore, are able to evade common immunological
      and chemical antiviral agents. In parallel, virus genomes cannot tolerate a
      further increase in mutation rate: Experimental evidence exists that even few
      additional mutations are sufficient for the extinction of a viral population. A
      future antiviral strategy might therefore aim at increasing the error-producing
      capacity of viral replication enzymes. We employed the principles of directed
      evolution and developed a scheme for the stringent positive selection of error
      prone polymerase activity. A mutant T7 RNA polymerase with a nucleotide
      substitution error rate at least 20-fold greater than that of the wild-type was
      selected. This enzyme synthesized highly heterogeneous RNA products in vitro or
      in vivo and also decreased the replication efficiency of wild-type bacteriophage
      T7 during infection.

PMID- 11828446
TI  - In vitro and in vivo ligand binding to the 5HT(3) serotonin receptor
      characterised by time-resolved fluorescence spectroscopy.
AB  - The binding of the fluorescein-labelled antagonist GR-flu ([1,2,3,9-tetrahydro-3
      [(5-methyl-1H-imidazol-4-yl)methyl]-9-(3-amino-(N
      fluoresceinthiocarbamoyl)propyl)-4H-carbazol-4-one]) to a purified, detergent
      solubilised ligand-gated ion channel, the type-3 serotonin (5-hydroxytryptamine,
      5HT) receptor (5HT(3)R), was characterised by frequency-domain time-resolved
      fluorescence spectroscopy (TRFS). Detailed understanding of how ligands interact
      with the homopentameric receptor was obtained. While a 1:1 stoichiometry was
      observed for the GR-flu-receptor complex, the agonist quipazine bound
      cooperatively to the receptor, suggesting multiple binding sites for this ligand.
      The GR-flu-binding site of the receptor was proven to provide an acidic
      environment as shown by determining the fraction of bound GR-flu in the
      protonated state. Fluorescence anisotropy relaxation experiments indicated a
      hindered but still high mobility for the receptor-bound GR-flu. Hence, the
      binding site is expected to present a wide opening to the ligand. Finally, we
      succeeded in measuring the binding of GR-flu to 5HT(3) receptors in live cells.
      These results show that the purified and the native receptor behave identically
      and demonstrate that time-resolved fluorescence measurements are suited to
      selectively investigate biomolecular interactions in live cells.

PMID- 11828448
TI  - Synthesis of minigramicidin ion channels and test of their hydrophobic match with
      the membrane.

PMID- 11828449
TI  - Enhancement of alphaPNA binding affinity and specificity through hydrophobic
      interactions.

PMID- 11828450
TI  - RNA interference and small interfering RNAs.

PMID- 11828451
TI  - Carbon-detected NMR experiments to investigate structure and dynamics of
      biological macromolecules.
AB  - We have started to develop new NMR pulse sequences that detect carbon
      magnetization during the acquisition period. These experiments have become
      possible with the recent introduction of cryogenic probe heads. We show that a
      careful design of these carbon-detected experiments can at least partially
      compensate for the inherent lower sensitivity of carbon detection compared to
      proton detection. We discuss potential applications of carbon detection and
      demonstrate a deconvolution technique that removes the effects of carbon-carbon
      couplings from the spectra.

PMID- 11828453
TI  - Nucleic acid supercoiling as a means for ionic switching of DNA--nanoparticle
      networks.
AB  - Oligomeric nanoparticle networks, generated by the self-assembly of bis
      biotinylated double-stranded DNA fragments and streptavidin, have been studied by
      scanning force microscopy (SFM). SFM imaging revealed the presence within the
      networks of irregular thick DNA molecules, which were often associated with
      distinct, Y-shaped structural elements. Closer analysis revealed that the Y
      structures are formed by condensation (thickening and shortening) of two DNA
      fragments, most likely through the supercoiling of two DNA molecules bound to
      adjacent binding sites of the streptavidin particle. The frequency of
      supercoiling was found to be dependent on the ionic strength applied during the
      immobilization of the oligomeric networks on mica surfaces. Potential
      applications of the structural changes as a means for constructing ion-dependent
      molecular switches in nanomaterials are discussed.

PMID- 11828452
TI  - Selection of metalloenzymes by catalytic activity using phage display and
      catalytic elution.
AB  - The metallo-beta-lactamase betaLII from Bacillus cereus 569/H/9 was displayed on
      the filamentous phage fd. The phage-bound enzyme fd-betaLII was shown to be
      active on benzylpenicillin as substrate; it could be inactivated by complexation
      of the essential zinc(II) ion with EDTA and reactivated by addition of a zinc(II)
      salt. A selection process was designed to extract active phage-bound enzymes from
      libraries of mutants in three steps: 1. inactivation of active phage-bound
      enzymes by metal ion complexation, 2. binding to substrate-coated magnetic beads,
      3. release of phages capable of transforming the substrate into product upon zinc
      salt addition. The selection process was first successfully tested on model
      mixtures containing fd-betaLII plus either a dummy phage, a phage displaying an
      inactive mutant of the serine beta-lactamase TEM-1, or inactive and low-activity
      mutants of betaLII. The selection was then applied to extract active phage-bound
      enzymes from a library of mutants generated by mutagenic polymerase chain
      reaction (PCR). The activity of the library was shown to increase 60-fold after
      two rounds of selection. Eleven clones from the second round were randomly picked
      for sequencing and to characterize their activity and stability.

PMID- 11828454
TI  - Stereoselective recognition of monolayers of cholesterol, ent-cholesterol, and
      epicholesterol by an antibody.
AB  - The interaction between a monoclonal antibody and four distinct monolayers with
      varying degrees of structural, chemical, and stereochemical similarity were
      studied and quantified. The antibody, raised and selected against cholesterol
      monohydrate crystals, interacts with cholesterol monolayers stereospecifically,
      but not enantiospecifically. Monolayers of ent-cholesterol molecules, which are
      chemically identical to cholesterol and whose structure is the exact mirror image
      of the cholesterol monolayer, interact with the antibody to the same extent as
      the cholesterol monolayers. The affinity of the antibody for both enantiomeric
      monolayers is extremely high. However, the antibody does not interact with
      monolayers of epicholesterol, which is an epimer of cholesterol: The hydroxy
      group in epicholesterol is in the 3alpha position rather than in the 3beta
      position, imposing a different angle between the hydroxy group and the rigid
      steroid backbone, and a different packing of the molecules. Monolayers of
      triacontanol, a long-chain primary aliphatic alcohol, interact with the antibody
      to a lesser extent than the cholesterol and ent-cholesterol monolayers,
      presumably due to the structural flexibility of the triacontanol molecule. The
      lack of chiral discrimination by the antibody is thus correlated to the level at
      which the chirality is exposed at the surface of the monolayers.

PMID- 11828455
TI  - Backbone and side-chain 13C and 15N signal assignments of the alpha-spectrin SH3
      domain by magic angle spinning solid-state NMR at 17.6 Tesla.
AB  - The backbone and side-chain 13C and 15N signals of a solid 62-residue (u-13C,15N)
      labelled protein containing the alpha-spectrin SH3 domain were assigned by two
      dimensional (2D) magic angle spinning (MAS) 15N-13C and 13C-13C dipolar
      correlation spectroscopy at 17.6 T. The side-chain signal sets of the individual
      amino acids were identified by 2D 13C-13C proton-driven spin diffusion and
      dipolar recoupling experiments. Correlations to the respective backbone nitrogen
      signals were established by 2D NCACX (CX=any carbon atom) experiments, which
      contain a proton-nitrogen and a nitrogen-carbon cross-polarisation step followed
      by a carbon-carbon homonuclear transfer unit. Interresidue correlations leading
      to sequence-specific assignments were obtained from 2D NCOCX experiments. The
      assignment is nearly complete for the SH3 domain residues 7-61, while the signals
      of the N- and C-terminal residues 1-6 and 62, respectively, outside the domain
      boundaries are not detected in our MAS spectra. The resolution observed in these
      spectra raises expectations that receptor-bound protein ligands and slightly
      larger proteins (up to 20 kDa) can be readily assigned in the near future by
      using three-dimensional versions of the applied or analogous techniques.

PMID- 11828456
TI  - cycloSaligenyl-5-[(E)-2-bromovinyl]-2'-deoxyuridine monophosphate (cycloSal
      BVDUMP) pronucleotides active against Epstein-Barr virus.

PMID- 11828457
TI  - Synthesis and applications of chemical probes for human O6-alkylguanine-DNA
      alkyltransferase.

PMID- 11828459
TI  - Thiooligosaccharides as tools for structural biology.
AB  - Oligosaccharides in which at least one glycosidic oxygen atom is replaced with a
      sulfur atom can be routinely synthesized and act as competitive inhibitors of
      various glycoside hydrolases. Recent studies using both X-ray crystallography and
      other biophysical techniques provide structural insight into binding,
      recognition, and the catalytic mechanism of action of these enzymes.

PMID- 11828458
TI  - Molecular recognition of complementary liposomes in modeling cell-cell
      recognition.

PMID- 11828460
TI  - Mixed-linkage cellooligosaccharides: a new class of glycoside hydrolase
      inhibitors.
AB  - A new class of inhibitors for beta-D-glycoside hydrolases, in which a single
      alpha-(1-->4)-glycosidic bond is incorporated into an otherwise all-beta-(1-->4)
      linked oligosaccharide, is described. Such mixed beta/alpha-linkage
      cellooligosaccharides are not transition-state mimics, but instead are capable of
      utilising binding energy from numerous subsites, spanning either side of the
      catalytic centre, without the need for substrate distortion. This binding is
      significant; a mixed alpha/beta-D-tetrasaccharide acts competitively on a number
      of cellulases, displaying inhibition constants in the range of 40-300 microM.
      Using the Bacillus agaradhaerens enzyme Cel5A as a model system, one such mixed
      beta/alpha-cellooligosaccharide, methyl 4(II),4(III)-dithio-alpha-cellobiosyl-(1-
      >4)-beta-cellobioside, displays a K(i) value of 100 microM, an inhibition at
      least 150 times better than is observed with an equivalent all-beta-linked
      compound. The three-dimensional structure of B. agaradhaerens Cel5A in complex
      with methyl 4(II),4(III)-dithio-alpha-cellobiosyl-(1-->4)-beta-cellobioside has
      been determined at 1.8 A resolution. This confirms the expected mode of binding
      in which the ligand, with all four pyranosides in the (4)C(1) chair conformation,
      occupies the -3, -2 and +1 subsites whilst evading the catalytic (-1) subsite.
      Such "by-pass" compounds offer great scope for the development of a new class of
      beta-D-glycoside hydrolase inhibitors.

PMID- 11828461
TI  - Carboranyl bisglycosides for the treatment of cancer by boron neutron capture
      therapy.
AB  - Boron neutron capture therapy is a special type of radiotherapy for the treatment
      of cancer by using boron compounds. Problems often arise from the low water
      solubility of these compounds, their unselective uptake into the cancer cells,
      and their toxicity. Here we describe the novel water-soluble ortho-carboranyl
      bisglycosides 7 and 10 containing either lactose or glucose and the mixed
      bisglycosides 1 and 28 containing glucose, mannose, and galactose. The carboranyl
      bisglycosides show almost no toxicity toward bronchial carcinoma cells of line
      A549 up to a concentration of 0.50 mM. As anticipated, these compounds exhibit
      nearly no uptake into C6 glioma cells; they can therefore be used for a selective
      delivery into malignant cells by using conjugates of glycohydrolases and
      monoclonal antibodies which bind to tumor-associated antigens, since by enzymatic
      hydrolysis the bisglycosides are transformed into lipophilic compounds.

PMID- 11828462
TI  - Pure and scrambled self-aggregates prepared with zinc analogues of
      bacteriochlorophylls c and d.
AB  - Zinc analogues of bacteriochlorophylls c and d self-assembled in aqueous media
      with phospholipids. A methanol solution of zinc chlorin and alpha-lecithin was
      put in a cellulose tube and the inner methanol solvent was gradually replaced
      with water by dialysis to form the self-assembled oligomers. Visible absorption
      spectra of the aqueous solution showed that zinc chlorins formed J-aggregates
      within the hydrophobic core of alpha-lecithin assemblies and that the
      supramolecular structure of the aggregates depended upon the stereochemistry at
      the 3(1)-position and the alkyl substituents at the 8-, 12-, and 17(4)-positions
      of the zinc chlorin. When the aqueous aggregates were prepared with a mixture of
      3(1)-epimers and/or 8-, 12-, or 17(4)-homologues of zinc 3(1)-hydroxy-13(1)
      oxochlorins, the structurally distinct components coaggregated to make scrambled
      oligomers. However, during the dialysis, zinc 3(1)-hydroxy- and 7(1)-hydroxy
      13(1)-oxochlorins slowly individually aggregated to give two structurally
      different oligomer units in the cellulose tube. In contrast, if the two zinc
      chlorin components rapidly self-assembled in an aqueous medium, these components
      coaggregated to form scrambled oligomers. The present study shows that both the
      molecular structure of the pigments and the speed of the oligomerization
      determine the molecular arrangement in chlorosome-type self-assembled oligomers.

PMID- 11828463
TI  - Inhibition studies of porphobilinogen synthase from Escherichia coli
      differentiating between the two recognition sites.
AB  - Porphobilinogen synthase condenses two molecules of 5-aminolevulinate in an
      asymmetric way. This unusual transformation requires a selective recognition and
      differentiation between the substrates ending up in the A site or in the P site
      of porphobilinogen synthase. Studies of inhibitors based on the key intermediate
      first postulated by Jordan allowed differentiation of the two recognition sites.
      The P site, whose structure is known from X-ray crystallographic studies,
      tolerates ester functions well. The A site interacts very strongly with nitro
      groups, but is not very tolerant to ester functions. This differentiation is a
      central factor in the asymmetric handling of the two identical substrates.
      Finally, it could be shown that the keto group of the substrate bound at the A
      site is not only essential for the recognition, but that an increase in
      electrophilicity of the carbon atom also increases the inhibition potency
      considerably. This has important consequences for the recognition process at the
      A site, whose exact structure is not yet known.

PMID- 11828464
TI  - The highly exposed loop region in mammalian purple acid phosphatase controls the
      catalytic activity.
AB  - Recombinant human purple acid phosphatase (recHPAP) provides a convenient
      experimental system for assessing the relationship between molecular structure
      and enzymatic activity in mammalian purple acid phosphatases (PAPs). recHPAP is a
      monomeric protein with properties similar to those of uteroferrin (Uf) and other
      PAPs isolated as single polypeptide chains, but its properties differ
      significantly from those of bovine spleen PAP (BSPAP) and other PAPs isolated as
      proteolytically "clipped" forms. Incubation of recHPAP with trypsin results in
      proteolytic cleavage in an exposed region near the active site. The product is a
      tightly associated two-subunit protein whose collective spectroscopic and
      kinetics properties resemble those of BSPAP. These results demonstrate that the
      differences in spectroscopic and kinetics properties previously reported for
      mammalian PAPs are the result of proteolytic cleavage. Mass spectrometry shows
      that a three-residue segment, D-V-K, within the loop region is excised by
      trypsin. This finding suggests that important interactions between residues in
      the excised loop and one or more of the groups that participate in catalysis are
      lost or altered upon proteolytic cleavage. Analysis of available structural data
      indicates that the most important such interaction is that between Asp 146 in the
      exposed loop and active-site residues Asn 91 and His 92. Loss of this interaction
      should result in both an increase in the Lewis acidity of the Fe(II) ion and an
      increase in the nucleophilicity of the Fe(III)-bound hydroxide ion. Proteolytic
      cleavage thus constitutes a potential physiological mechanism for regulating the
      activity of PAP in vivo.

PMID- 11828465
TI  - Amino(hydroxymethyl)cyclopentanetriols, an emerging class of potent glycosidase
      inhibitors--Part I: Synthesis and evaluation of beta-D-pyranoside analogues in
      the manno, gluco, galacto, and GlcNAc series.

PMID- 11828466
TI  - Amino(hydroxymethyl)cyclopentanetriols, an emerging class of potent glycosidase
      inhibitors--Part II: Synthesis, evaluation, and optimization of beta-D
      galactopyranoside analogues.

PMID- 11828467
TI  - Solution structure of n-type DNA oligomers possessing a covalently cross-linked
      Watson-Crick base pair model.

PMID- 11828468
TI  - Preparation of symmetrical and unsymmetrical DNA-protein conjugates with DNA as a
      molecular scaffold.

PMID- 11828469
TI  - Cytochrome C oxidase and the regulation of oxidative phosphorylation.
AB  - Life of higher organisms is essentially dependent on the efficient synthesis of
      ATP by oxidative phosphorylation in mitochondria. An important and as yet
      unsolved question of energy metabolism is how are the variable rates of ATP
      synthesis at maximal work load during exercise or mental work and at rest or
      during sleep regulated. This article reviews our present knowledge on the
      structure of bacterial and eukaryotic cytochrome c oxidases and correlates it
      with recent results on the regulatory functions of nuclear-coded subunits of the
      eukaryotic enzyme, which are absent from the bacterial enzyme. A new molecular
      hypothesis on the physiological regulation of oxidative phosphorylation is
      proposed, assuming a hormonally controlled dynamic equilibrium in vivo between
      two states of energy metabolism, a relaxed state with low ROS (reactive oxygen
      species) formation, and an excited state with elevated formation of ROS, which
      are known to accelerate aging and to cause degenerative diseases and cancer. The
      hypothesis is based on the allosteric ATP inhibition of cytochrome c oxidase at
      high intramitochondrial ATP/ADP ratios ("second mechanism of respiratory
      control"), which is switched on by cAMP-dependent phosphorylation and switched
      off by calcium-induced dephosphorylation of the enzyme.

PMID- 11828470
TI  - Enzymes for peptide cyclization.

PMID- 11828471
TI  - Catalytic molecular beacons.
AB  - We have constructed catalytic molecular beacons from a hammerhead-type
      deoxyribozyme by a modular design. The deoxyribozyme was engineered to contain a
      molecular beacon stem-loop module that, when closed, inhibits the deoxyribozyme
      module and is complementary to a target oligonucleotide. Binding of target
      oligonucleotides opens the beacon stem-loop and allosterically activates the
      deoxyribozyme module, which amplifies the recognition event through cleavage of a
      doubly labeled fluorescent substrate. The customized modular design of catalytic
      molecular beacons allows for any two single-stranded oligonucleotide sequences to
      be distinguished in homogenous solution in a single step. Our constructs
      demonstrate that antisense conformational triggers based on molecular beacons can
      be used to initiate catalytic events. The selectivity of the system is sufficient
      for analytical applications and has potential for the construction of
      deoxyribozyme-based drug delivery tools specifically activated in cells
      containing somatic mutations.

PMID- 11828472
TI  - Thermodynamic control of electron transfer rates in multicentre redox proteins.
AB  - In the analysis of kinetic data from multicentre redox proteins, it is essential
      to distinguish between the observable macroscopic rate constants and the
      structurally relevant microscopic properties. This distinction is complicated by
      the existence of interactions between centres. The problem is illustrated by the
      case of two interacting redox centres and generalised for the analysis of stopped
      flow kinetic data for the reduction of cytochrome c(3), in which four redox
      centres and at least one proteolytic centre are mutually interacting. It is shown
      that fast intramolecular electron transfer, which is typical of many multicentre
      redox proteins, and, where present, fast proton exchange, ensure that only N rate
      constants can be measured for a protein with N redox centres. The equations that
      relate the observable macroscopic rate constants to the microscopic rate
      constants of individual centres depend on a set of parameters that can be
      approximated by using the Marcus theory of electron transfer together with a set
      of reasonable assumptions. The results are tested by fitting experimental data
      for the reduction of cytochrome c(3) by sodium dithionite, including its pH
      dependence.

PMID- 11828473
TI  - Natural deuterium distribution in long-chain fatty acids is nonstatistical: a
      site-specific study by quantitative (2)H NMR spectroscopy.
AB  - Quantitative (2)H NMR spectroscopy has been used to study the site-specific
      natural occurrence of (2)H in common unsaturated fatty acids. A marked
      nonstatistical isotopic distribution of (2)H is observed in both methyl oleate
      and methyl linoleate. By chemical modification, the internal isotopic (2)H
      signatures of these products have been partially accessed. Notably, it can be
      seen that (1) the sites of desaturation show a strong impoverishment at only one
      ethylenic position of each desaturation; (2) the level of impoverishment reflects
      the source of the hydrogen atoms present; and (3) a gradient of (2)H content
      occurs along the chain. These effects can in part be related to the mechanisms
      proposed for the enzymes responsible for the various steps of biosynthesis of
      unsaturated fatty acids in plants.

PMID- 11828474
TI  - Crystal structure of a synthetic cyclodecapeptide for template-assembled
      synthetic protein design.
AB  - The structural prototype of a new generation of regioselectively addressable
      functionalized templates (RAFTs) for use in protein de novo design has been
      synthesized and crystallized. The structure of the aromatically substituted
      cyclodecapeptide was determined by X-ray diffraction; it consists of an
      antiparallel beta sheet spanned by heterochirally induced type IIprime prime or
      minute beta turns, similar to that observed in gramicidin S. The three
      dimensional structure of the artificial template was also examined by an NMR
      spectroscopic analysis in solution and shown to be compatible with a beta-sheet
      plane suitable for accommodating secondary functional peptide fragments for the
      synthesis of template-assembled synthetic proteins (TASPs).

PMID- 11828475
TI  - Dynamic deconvolution of a pre-equilibrated dynamic combinatorial library of
      acetylcholinesterase inhibitors.
AB  - A dynamic combinatorial library composed of interconverting acylhydrazones has
      been generated and screened towards inhibition of acetylcholinesterase from the
      electric ray Torpedo marmorata. Starting from a small set (13) of initial
      hydrazide and aldehyde building blocks, a library containing possibly 66
      different species was obtained in a single operation. Of all possible
      acylhydrazones formed, active compounds containing two terminal cationic
      recognition groups separated by an appropriate distance, permitting two-site
      binding, could be rapidly identified by using a dynamic deconvolution--screening
      procedure, based on the sequential removal of starting building blocks. A very
      potent bis-pyridinium inhibitor (K(i)=1.09 nM, alphaK(i)=2.80 nM) was selected
      from the process and the contribution of various structural features to
      inhibitory potency was evaluated.

PMID- 11828477
TI  - Towards proto-cells: "primitive" lipid vesicles encapsulating giant DNA and its
      histone complex.

PMID- 11828476
TI  - The outstanding biological stability of beta- and gamma-peptides toward
      proteolytic enzymes: an in vitro investigation with fifteen peptidases.
AB  - A series of 36 linear and cyclic beta- and gamma-peptides consisting of as few as
      two, and as many as 15 residues, was offered as substrates to 15 commercially
      available proteases of bacterial, fungal, and eukaryotic origin, including a beta
      lactamase and amidases, as well as most vigorous, nonspecific proteases, such as
      the 20S proteasome from human erythrocytes. For comparison, an alpha
      eicosapeptide and standard substrates of the proteolytic enzymes were included in
      the investigation. Under conditions of complete cleavage of the alpha-peptide
      within 15 min the beta- and gamma-peptides were stable for at least 48 h.
      Inhibition studies with seven beta- and gamma-peptides and alpha-chymotrypsin
      show that the residual enzyme activity toward succinyl-Ala-Ala-Pro-Phe-p
      nitroanilide is unchanged within experimental error after incubation for 15 min
      with the peptide analogues. Thus, beta- and gamma-peptides with proteinogenic
      side chains, that is, consisting of the singly or doubly homologated natural
      alpha-amino acids (one or two CH(2) groups inserted in the backbone of each
      residue), are completely stable to common proteases, without inhibiting their
      normal activity (as demonstrated for alpha-chymotrypsin). This proteolytic
      stability of peptides built of homologated amino acids is a prerequisite for
      their potential use as drugs.

PMID- 11828478
TI  - Discovery of novel antibacterial agents active against methicillin-resistant
      Staphylococcus aureus from combinatorial benzopyran libraries.

PMID- 11828479
TI  - Cyberpills.

PMID- 11828480
TI  - A half-century of neurotransmitter research: impact on neurology and psychiatry
      (Nobel lecture).

PMID- 11828481
TI  - Fatty acid hydroperoxide lyase: a plant cytochrome p450 enzyme involved in wound
      healing and pest resistance.
AB  - Plants continuously have to defend themselves against life-threatening events
      such as drought, mechanical damage, temperature stress, and potential pathogens.
      Nowadays, more and more similarities between the defense mechanism of plants and
      that of animals are being discovered. In both cases, the lipoxygenase pathway
      plays an important role. In plants, products of this pathway are involved in
      wound healing, pest resistance, and signaling, or they have antimicrobial and
      antifungal activity. The first step in the lipoxygenase pathway is the reaction
      of linoleic or linolenic acids with molecular oxygen, catalyzed by the enzyme
      lipoxygenase. The hydroperoxy fatty acids thus formed are highly reactive and
      dangerous for the plant and therefore further metabolized by other enzymes such
      as allene oxide synthase, hydroperoxide lyase, peroxygenase, or divinyl ether
      synthase. Recently, these enzymes have been characterized as a special class of
      cytochrome P450 enzymes. Hydroperoxide lyases cleave the lipoxygenase products,
      resulting in the formation of omega-oxo acids and volatile C6- and C9-aldehydes
      and -alcohols. These compounds are major contributors to the characteristic
      "fresh green" odor of fruit and vegetables. They are widely used as food flavors,
      for example, to restore the freshness of food after sterilization processes. The
      low abundance of these compounds in nature and the high demand make it necessary
      to synthesize them on a large scale. Lipoxygenase and hydroperoxide lyase are
      suitable biocatalysts for the production of "natural" food flavors. In contrast
      to lipoxygenase, which has been extensively studied, little is yet known about
      hydroperoxide lyase. Hydroperoxide lyases from different organisms have been
      isolated, and a few genes have been published lately. However, the structure and
      reaction mechanism of this enzyme are still unclear. The identification of this
      enzyme as a cytochrome P450 sheds new light on its structure and possible
      reaction mechanism, whereas recombinant expression brings a biocatalytic
      application into sight.

PMID- 11828482
TI  - Sorting of preproteins into mitochondria.

PMID- 11828483
TI  - G-protein-coupled receptors for light: the three-dimensional structure of
      rhodopsin.

PMID- 11828484
TI  - Improving Escherichia coli alkaline phosphatase efficacy by additional mutations
      inside and outside the catalytic pocket.
AB  - We describe a strategy that allowed us to confer on a bacterial (E. coli)
      alkaline phosphatase (AP) the high catalytic activity of the mammalian enzyme
      while maintaining its high thermostability. First, we identified mutations, at
      positions other than those occupied by essential catalytic residues, which
      inactivate the bacterial enzyme without destroying its overall conformation. We
      transferred concomitantly into the bacterial enzyme four residues of the
      mammalian enzyme, two being in the catalytic pocket and two being outside.
      Second, the gene encoding the inactive mutant was submitted to random
      mutagenesis. Enzyme activity was restored upon the single mutation D330N, at a
      position that is 12 A away from the center of the catalytic pocket. Third, this
      mutation was combined with other mutations previously reported to increase AP
      activity slightly in the presence of magnesium. As a result, at pH 10.0 the
      phosphatase activity of both mutants D330N/D153H and D330N/D153G was 17-fold
      higher than that of the wild-type AP. Strikingly, although the two individual
      mutations D153H and D153G destabilize the enzyme, the double mutant D330N/D153G
      remained highly stable (T(m)=87 degrees C). Moreover, when combining the
      phosphatase and transferase activities, the catalytic activity of the mutant
      D330N/D153G increased 40-fold (k(cat)=3200 s-1) relative to that of the wild-type
      enzyme (k(cat)=80 s-1). Due to the simultaneous increase in K(m), the resulting
      k(cat)/K(m) value was only increased by a factor of two. Therefore, a single
      mutation occurring outside a catalytic pocket can dramatically control not only
      the activity of an enzyme, but also its thermostability. Preliminary
      crystallographic data of a covalent D330N/D153G enzyme-phosphate complex show
      that the phosphate group has significantly moved away from the catalytic pocket,
      relative to its position in the structure of another mutant previously reported.

PMID- 11828485
TI  - Metal ion effects on the cis/trans isomerization equilibrium of proline in short
      chain peptides: a solution NMR study.
AB  - The effect of copper(II) ions on the probabilities of existence of the four
      detectable conformers of the tetrapeptide Tyr-Pro-Phe-Pro (beta-casomorphin 4) in
      [2H6]DMSO was investigated by 1H NMR spectroscopy. Integration of the Phe-NH
      signals provided the relative populations in the free state as
      tt/tc/ct/cc=28:34:29:9 at 293 K (c=cis, t=trans). Copper(II) was shown to bind to
      all four isomers, yielding complexes with two different structures, depending on
      the conformation of Pro(2). The interpretation of paramagnetic relaxation rates
      of Pro(2)-Halpha signals provided the corresponding isomeric probabilities in the
      metal-bound state as 13:36:20:31. The observed stabilization of the conformation
      with the lowest probability of existence (cc) may be relevant for the biological
      role of copper and other metal ions.

PMID- 11828486
TI  - Re-face stereospecificity of methylenetetrahydromethanopterin and
      methylenetetrahydrofolate dehydrogenases is predetermined by intrinsic properties
      of the substrate.
AB  - Four different dehydrogenases are known that catalyse the reversible
      dehydrogenation of N5,N10-methylenetetrahydromethanopterin (methylene-H4MPT) or
      N5,N10-methylenetetrahydrofolate (methylene-H4F) to the respective N5,N10
      methenyl compounds. Sequence comparison indicates that the four enzymes are
      phylogenetically unrelated. They all catalyse the Re-face-stereospecific removal
      of the pro-R hydrogen atom of the coenzyme's methylene group. The Re-face
      stereospecificity is in contrast to the finding that in solution the pro-S
      hydrogen atom of methylene-H4MPT and of methylene-H4F is more reactive to
      heterolytic cleavage. For a better understanding we determined the conformations
      of methylene-H4MPT in solution and when enzyme-bound by using NMR spectroscopy
      and semiempirical quantum mechanical calculations. For the conformation free in
      solution we find an envelope conformation for the imidazolidine ring, with the
      flap at N10. The methylene pro-S C-H bond is anticlinal and the methylene pro-R C
      H bond is synclinal to the lone electron pair of N10. Semiempirical quantum
      mechanical calculations of heats of formation of methylene-H4MPT and methylene
      H4F indicate that changing this conformation into an activated one in which the
      pro-S C-H bond is antiperiplanar, resulting in the preformation of the leaving
      hydride, would require a deltadeltaH(f) of +53 kJ mol-1 for methylene-H4MPT and
      of +51 kJ mol-1 for methylene-H4F. This is almost twice the energy required to
      force the imidazolidine ring in the enzyme-bound conformation of methylene-H4MPT
      (+29 kJ mol-1) or of methylene-H4F (+35 kJ mol-1) into an activated conformation
      in which the pro-R hydrogen atom is antiperiplanar to the lone electron pair of
      N10. The much lower energy for pro-R hydrogen activation thus probably
      predetermines the Re-face stereospecificity of the four dehydrogenases. Results
      are also presented explaining why the chemical reduction of methenyl-H4MPT+ and
      methenyl-H4F+ with NaBD4 proceeds Si-face-specific, in contrast to the enzyme
      catalysed reaction.

PMID- 11828487
TI  - Photoresponsive dendritic azobenzene peptides.
AB  - Two dendritic peptides containing a branched lysine core and up to eight
      azobenzene moieties in the periphery were synthesized on solid support employing
      the omega-amino acid 4-(aminomethyl)phenylazobenzoic acid. With an additional
      peptidic tail consisting of an oligolysine portion, water solubility was achieved
      for the dendrimers, which allowed for the characterization of the cis/trans
      photoisomerization of the dendritic azobenzene species in both organic and
      aqueous media. Despite the interactions between the chromophores, which occur
      particularly in aqueous media, at higher dilution the photoisomerization process
      was found to proceed to extents that should permit photomodulation of molecular
      recognition processes between ligands grafted to the photosensitive azobenzene
      units and receptor molecules.

PMID- 11828488
TI  - Locating the metal ion in calcium-binding proteins by using cerium(III) as a
      probe.
AB  - The detection and assignment of NMR spectroscopic signals of carbon atoms from
      carbonyl and carboxylate groups in the loop hosting the Ce(III) ion was performed
      for the cerium-substituted calcium-binding protein calbindin D9k. This provided a
      tool to characterize in solution the first coordination sphere of the metal ion.
      Due to the well-documented possibility of replacing calcium with metal ions of
      the Ln(III) series, this approach turns out to be extremely efficient for
      characterizing in solution the coordination of calcium ions in proteins,
      independently of the availability of X-ray crystal structures. The present
      approach completes the structural characterization of lanthanide-substituted
      calcium-binding proteins, for which the role of long-range constraints arising
      from hyperfine interaction and self-orientation has already been assessed.

PMID- 11828489
TI  - Novel dications with unfused aromatic systems: trithiophene and trifuran
      derivatives of furimidazoline.
AB  - We report the synthesis, interaction with DNA, topoisomerase II inhibition, and
      cytotoxicity of two novel unfused aromatic dications derived from the
      antimicrobial agent furimidazoline. The central diphenylfuran core of
      furimidazoline has been replaced with a trithiophene (DB358) or a trifuran
      (DB669) unit and the terminal imidazoline groups were preserved. The strength and
      mode of binding of the drugs to nucleic acids were investigated by complementary
      spectroscopic techniques including spectrophotometric, surface plasmon resonance,
      circular and linear dichroism measurements. The trifuran derivative forms
      intercalation complexes with double-stranded DNA, whereas the mode of binding of
      the trithiophene derivative varies depending on the drug/DNA ratio, as
      independently confirmed by NMR spectroscopic studies performed with (A-T)7 and (G
      C)7 oligomers. Two-dimensional NMR data provided a molecular model for the
      binding of DB358 within the minor groove of the AATT sequence of the
      decanucleotide d(GCGAATTCGC)(2). DNase I footprinting experiments confirmed the
      sequence-dependent binding of DB358 to DNA. The trithiophene derivative interacts
      preferentially with AT-rich sequences at low concentrations, but can accomodate
      GC sites at higher concentrations. DNA relaxation assays revealed that DB358
      stimulated DNA cleavage by topoisomerase II, in contrast to DB669. The
      substitution of N-alkylamidines for the imidazoline terminal groups abolished the
      capacity of the drug to poison topoisomerase II. At the cellular level, flow
      cytometry analysis indicated that DB358, which is about six times more cytotoxic
      than the trifuran analogue, induced a significant accumulation of HL-60 human
      leukemia cells in the G2/M phase. The incorporation of thiophene heterocycles
      appears as a convenient procedure to limit the strict AT selectivity of dications
      containing an extended unfused aromatic system and to design cytotoxic DNA
      intercalating agents acting as poisons for human topoisomerase II.

PMID- 11828490
TI  - Ras-mediated cleavage of a GTP analogue by a novel mechanism.
AB  - The small guanosine triphosphate (GTP) binding protein Ras is involved in many
      cellular signal transduction processes leading to cell growth, differentiation
      and apoptosis. Mutations in ras genes are found in a large number of human
      tumours. GTP hydrolysis, the process that normally leads to the transition of the
      Ras protein from the active (GTP-bound) form to the inactive (GDP-bound) form is
      impaired due to these oncogenic mutations. In contrast, the GTP analogue 3,4
      diaminobenzophenone(DABP)-phosphoramidate-GTP, a substrate for GTP-binding
      proteins, enables switching to the inactive GDP form in both wild-type and
      oncogenic Ras. Here we show by HPLC, mass spectrometry and NMR spectroscopy that
      the mechanism of this DABP-GTPase reaction is different from the physiological
      GTPase reaction. The gamma-phosphate group is not attacked by a nucleophilic
      water molecule, but rather by the aromatic amino group of the analogue, which
      leads to the generation of a stable cyclic diamidate product. These findings have
      potential implications for the development of anti-Ras drugs.

PMID- 11828491
TI  - Cloning, functional expression, and characterization of recombinant pig liver
      esterase.
AB  - The N-terminal amino acid sequence of pig liver esterase (PLE) from a commercial
      sample was determined and shown to match closely to a published sequence encoding
      a proline-beta-naphthylamidase from pig liver. Next, mRNA isolated from pig liver
      was transcribed into cDNA and primers deduced from the N-terminal sequence were
      used to clone the 1698 base pairs of PLE cDNA. Initial attempts to express the
      cDNA in Escherichia coli and Pichia pastoris with different expression vectors
      and secretion signal sequences failed. Only after deletion of the putative C
      terminal sequence His-Ala-Glu-Leu, usually considered as an endoplasmic reticulum
      retention signal, could heterologous expression of PLE be readily achieved in the
      methylotrophic yeast P. pastoris. Recombinant PLE (rPLE) was secreted into the
      medium and exhibited a specific activity of approximately 600 Umg(-1) and a
      Vmax/Km value of 139 micromolmin(-1)mM(-1) with p-nitrophenyl acetate as a
      substrate. Activity staining of renatured sodium dodecylsulfate-polyacrylamide
      gels gave a single band with esterolytic activity for rPLE, whereas several bands
      are visible in crude commercial PLE preparations. This was confirmed by native
      gels, which also show that rPLE is active as a trimer. Biochemical
      characterization of the recombinant enzyme and comparison with properties of
      commercial PLE preparations as well as with published data confirmed that we
      expressed a single PLE isoenzyme which showed a high preference for proline-beta
      naphthylamide. This is a substrate specificity for the so-called gamma subunit of
      PLE. The optimum pH value and temperature for the recombinant PLE were 8.0 and 60
      degrees C, respectively. The determined molecular weight of the secreted enzyme
      was approximately 61-62 kDa, which closely matches the calculated value of 62.419
      kDa. The active site residues are located at Ser203, His448, and Asp97, and the
      typical consensus sequence motif for hydrolases was found around the active site
      serine (Gly-Glu-Ser-Ala-Gly).

PMID- 11828492
TI  - Could a diiron-containing four-helix-bundle protein have been a primitive oxygen
      reductase?

PMID- 11828493
TI  - Visualization of annexin I binding to calcium-induced phosphatidylserine domains.

PMID- 11828494
TI  - Electroactive monolayer substrates that selectively release adherent cells.

PMID- 11828495
TI  - Bionic catalyst design: a photochemical approach to artificial enzyme function.

PMID- 11828496
TI  - Chemistry: a way to the roots of biology.

PMID- 11828498
TI  - A biosynthetic classification of fungal and streptomycete fused-ring aromatic
      polyketides.
AB  - Polyketides are one of the largest and most structurally diverse classes of
      naturally occurring compounds, ranging from simple aromatic metabolites to
      complex macrocyclic lactones. Fungi and filamentous bacteria, particularly the
      actinomycetes, are major sources of polycyclic aromatic structures, which include
      many clinically important antibiotics and other useful metabolites. These fused
      ring polyketides are formed by the action of polyketide synthases (PKSs), which
      catalyse the assembly, folding and cross-linking of poly-beta-ketoacyl
      intermediates. In view of the taxonomic gulf between the eukaryotic fungi and
      prokaryotic bacteria, it is not surprising that they are rarely found to produce
      structurally identical fused-ring metabolites. A review of [(13)C(2)]acetate
      incorporation data has revealed consistent differences in the reported
      cyclisation patterns, which require regiospecifically distinct cross-linking of
      otherwise identical linear polyketide precursors. This observation provides the
      basis for a structural and biosynthetic classification of microbial fused-ring
      polyketides, which has a number of useful ramifications.

PMID- 11828499
TI  - In vitro selection of hammerhead ribozyme sequence variants.

PMID- 11828500
TI  - The structures of organelles and reticula: localised bioenergetics and
      metabolism.

PMID- 11828501
TI  - A protein pre-organized to trap the nucleotide moiety of coenzyme B(12): refined
      solution structure of the B(12)-binding subunit of glutamate mutase from
      Clostridium tetanomorphum.
AB  - Uniformly (13)C,(15)N-labeled MutS, the coenzyme B(12)-binding subunit of
      glutamate mutase from Clostridium tetanomorphum, was prepared by overexpression
      from an Escherichia coli strain. Multidimensional heteronuclear NMR spectroscopic
      experiments with aqueous solutions of (13)C,(15)N-labeled MutS provided signal
      assignments for roughly 90% of the 1025 hydrogen, 651 carbon, and 173 nitrogen
      atoms and resulted in about 1800 experimental restraints. Based on the
      information from the NMR experiments, the structure of MutS was calculated,
      confirming the earlier, less detailed structure obtained with (15)N-labeled MutS.
      The refined analysis allowed a precise determination of the secondary and
      tertiary structure including several crucial side chain interactions. The
      structures of (the apoprotein) MutS in solution and of the B(12)-binding subunit
      in the crystal of the corresponding homologous holoenzyme from Clostridium
      cochlearium differ only in a section that forms the well-structured helix alpha1
      in the crystal structure and that also comprises the cobalt-coordinating
      histidine residue. In the apoprotein MutS, this part of the B(12)-binding subunit
      is dynamic. The carboxy-terminal end of this section is conformationally flexible
      and has significant propensity for an alpha-helical structure ("nascent helix").
      This dynamic section in MutS is a decisive element for the binding of the
      nucleotide moiety of coenzyme B(12) and appears to be stabilized as a helix
      (alpha1) upon trapping of the nucleotide of the B(12) cofactor.

PMID- 11828502
TI  - Synthesis of epothilone analogues by antibody-catalyzed resolution of thiazole
      aldol synthons on a multigram scale. Biological consequences of C-13 alkylation
      of epothilones.
AB  - Three monoclonal aldolase antibodies (84G3, 85H6, and 93F3), generated against a
      beta-diketone hapten (II) by the reactive immunization technique, catalyzed
      highly enantioselective retro-aldol reactions of the racemic thiazole aldols 13
      20. Antibody 84G3 (0.0004-0.005 mol%) was used to resolve (+/-)-13-(+/-)-18 to
      afford compounds 13-18 in multigram quantities. Multiple 13-alkyl analogues of
      epothilone (7-12) and their trans isomers ((E)-7-(E)-12) were synthesized
      starting from thiazole aldols 13-18. Construction of the trisubstituted olefin
      moiety in compounds 7-12 and (E)-7-(E)-12 was catalyzed by Grubbs' catalyst (X).
      Initial biological testing with compounds 7-10 and their trans isomers showed
      that compounds 9, 10, and (E)-10 have appreciable tubulin polymerization and
      antiproliferative activities that approached those of epothilone C. The most
      active compound, (E)-9, even displayed potencies comparable to those observed for
      epothilones A and D. Interestingly, all trans analogues were more potent than
      their corresponding cis isomers. While introduction of an alkyl group at C-13 in
      the cis series led to an overall reduction in biological activity (compared to
      epothilone C), appropriate modification of the thiazole moiety (replacement of
      the 2-methyl substituent by a 2-methylthio group) was able to compensate for this
      loss. These results are encouraging in view of the expectation that epoxidations
      of these compounds should further increase their cellular activities. Thus,
      compounds 9, 10, and (E)-9 and (E)-10 represent highly promising candidates for
      further studies.

PMID- 11828503
TI  - cDNA - protein fusions: covalent protein - gene conjugates for the in vitro
      selection of peptides and proteins.
AB  - We report a method for the synthesis of covalent cDNA-protein fusions for protein
      display applications. A branched mRNA template was developed which carries a
      peptidyl acceptor and a reverse transcription primer at the 3'-end. Translation
      in vitro followed by reverse transcription produced a protein covalently bonded
      to its encoding cDNA. Both single- and double-stranded cDNA-protein fusions were
      prepared. cDNA-protein fusions are stable in alkali and resistant to
      ribonucleases. Their simple preparation and their resistance towards degradation
      should make cDNA-protein fusions a useful tool for the in vitro selection and
      evolution of high affinity ligands from large libraries of polypeptides.

PMID- 11828504
TI  - The activation of fibroblast growth factors by heparin: synthesis, structure, and
      biological activity of heparin-like oligosaccharides.
AB  - An effective strategy has been designed for the synthesis of oligosaccharides of
      different sizes structurally related to the regular region of heparin; this is
      illustrated by the preparation of hexasaccharide 1 and octasaccharide 2. This
      synthetic strategy provides the oligosaccharide sequence containing a D
      glucosamine unit at the nonreducing end that is not available either by enzymatic
      or chemical degradation of heparin. It may permit, after slight modifications,
      the preparation of oligosaccharide fragments with different charge distribution
      as well. NMR spectroscopy and molecular dynamics simulations have shown that the
      overall structure of 1 in solution is a stable right-hand helix with four
      residues per turn. Hexasaccharide 1 and, most likely, octasaccharide 2 are,
      therefore, chemically well-defined structural models of naturally occurring
      heparin-like oligosaccharides for use in binding and biological activity studies.
      Both compounds 1 and 2 induce the mitogenic activity of acid fibroblast growth
      factor (FGF1), with the half-maximum activating concentration of 2 being
      equivalent to that of heparin. Sedimentation equilibrium analysis with compound 2
      suggests that heparin-induced FGF1 dimerization is not an absolute requirement
      for biological activity.

PMID- 11828505
TI  - Dendrimer-activated solid supports for nucleic acid and protein microarrays.
AB  - The generation of chemically activated glass surfaces is of increasing interest
      for the production of microarrays containing DNA, proteins, and low-molecular
      weight components. We here report on a novel surface chemistry for highly
      efficient activation of glass slides. Our method is based on the initial
      modification of glass with primary amino groups using a protocol, specifically
      optimized for high aminosilylation yields, and in particular, for homogeneous
      surface coverages. In a following step the surface amino groups are activated
      with a homobifunctional linker, such as disuccinimidylglutarate (DSG) or 1,4
      phenylenediisothiocyanate (PDITC), and then allowed to react with a starburst
      dendrimer that contains 64 primary amino groups in its outer sphere.
      Subsequently, the dendritic monomers are activated and crosslinked with a
      homobifunctional spacer, either DSG or PDITC. This leads to the formation of a
      thin, chemically reactive polymer film, covalently affixed to the glass
      substrate, which can directly be used for the covalent attachment of amino
      modified components, such as oligonucleotides. The resulting DNA microarrays were
      studied by means of nucleic acid hybridization experiments using fluorophor
      labeled complementary oligonucleotide targets. The results indicate that the
      novel dendrimer-activated surfaces display a surface coverage with capture
      oligomers about twofold greater than that with conventional microarrays
      containing linear chemical linkers. In addition, the experiments suggest that the
      hybridization occurs with decreased steric hindrance, likely a consequence of the
      long, flexible linker chain between the surface and the DNA oligomer. The
      surfaces were found to be resistant against repeated alkaline regeneration
      procedures, which is likely a consequence of the crosslinked polymeric structure
      of the dendrimer film. The high stability allows multiple hybridization
      experiments without significant loss of signal intensity. The versatility of the
      dendrimer surfaces is also demonstrated by the covalent immobilization of
      streptavidin as a model protein.

PMID- 11828506
TI  - Functional display of active bovine adrenodoxin on the surface of E. coli by
      chemical incorporation of the [2Fe-2S] cluster.
AB  - The display of heterologous proteins on the surface of living cells bears
      promising options for a wide variety of biotechnological applications. Up to now,
      however, cellular surface display was merely restricted to simple polypeptide
      chains. Here we present for the first time the efficient display of a protein
      (bovine adrenodoxin) that contains an inorganic, prosthetic group in its active
      form on the surface of Escherichia coli. For this purpose apo-adrenodoxin was
      transported to the cell surface and anchored within the outer membrane by the
      autotransporter pathway. Incorporation of the iron-sulfur cluster was achieved by
      a single-vial, one-step titration under anaerobic conditions. The biological
      function of surface-displayed holo-adrenodoxin could be established through
      adrenodoxin-dependent steroid conversion by two different cytochrome P450 enzymes
      and the number of functional molecules on the cell surface could be determined to
      be more than 10(5) per cell. Neither the expression of adrenodoxin nor the
      incorporation of the chemical iron-sulfur cluster reduced the viability of the
      bacterial cells.

PMID- 11828507
TI  - In vivo oxo transfer: reactions of native and W-substituted dimethyl sulfoxide
      reductase monitored by (1)H NMR spectroscopy.

PMID- 11828508
TI  - Studies on DNA cleavage by cytotoxic pyrrole alkaloids reveal the distinctly
      different behavior of roseophilin and prodigiosin derivatives.

PMID- 11828509
TI  - The chemistry and biology of ratjadone.

PMID- 11828550
TI  - Educatione ad excelentiam--ten years of the Croatian medical journal.

PMID- 11828551
TI  - Scientific biomedical journals in Croatia.
AB  - AIM: To assess the current situation in biomedical journal publishing in Croatia,
      according to the journals editorial and publishing characteristics. METHOD: A
      survey questionnaire with 38 questions was sent to the editors-in-chief of 43
      biomedical journals in Croatia. Thirty-seven journals were analyzed. RESULTS: In
      2000, there were 14 general and 23 specialized biomedical journals in Croatia.
      Twenty-five journals received financial support from the government. Six journals
      were indexed in MEDLINE, with two of them also in Current Contents, 20 in other
      bibliographic databases, and 11 were not indexed at all. Twelve journals
      published articles in English, 11 in Croatian, and 14 in either English or
      Croatian. Only 9 journals were available on-line: 5 offered abstracts only and 4
      offered full-text articles. There were more indexed than non-indexed journals
      that were financially supported by the government (p=0.031) and published in
      English or either English or Croatian (p=0.011). Indexed journals published more
      pages (p=0.020) and received more articles (p=0.030) per year. Five journals
      provided salary for the editorial staff and 4 paid the reviewers services. Median
      number of subscribers was 250 (range, 0-7,000) and median circulation 650 (range,
      300-7,200). Finances, number and quality of articles, and problems with the
      review process were perceived by editors as the most important problems.
      CONCLUSION: Many journals had financial problems despite receiving governmental
      or other support. Low number/quality of articles received and inefficient review
      process could reflect the self-containment of Croatian medical community, which
      comprises around 11,000 physicians and dentists. Large ranges in circulation,
      number of subscribers, and number of pages published per year, as well as in
      indexing rates, might imply large differences among the journals in their target
      readership and editorial policies and performance.

PMID- 11828552
TI  - Superoxide dismutase and glutathione peroxidase in erythrocytes of patients with
      iron deficiency anemia: effects of different treatment modalities.
AB  - AIM: To test whether the activities of erythrocyte superoxide dismutase (SOD) and
      glutathione peroxidase (GSH-Px) can be affected by oral iron (OI) treatment,
      parenteral iron (PI) treatment, and parenteral iron treatment with vitamin E
      supplementation (PIE) in iron deficiency anemia. METHODS: Twenty-eight patients
      with iron deficiency anemia and 18 healthy controls were included in the study.
      Anemic patients were systematically allocated into 3 treatment groups. The first
      group (n=8) received OI, the second group (n=10) PI, and the third group (n=10)
      PIE. SOD and GSH-Px activities were determined using commercial kits. RESULTS:
      Before the treatment, SOD activity was significantly lower in anemic patients
      than in the control group (Kruskal-Wallis test, p<0.05). After the treatment, SOD
      activity significantly increased in all three patient groups and reached the
      values found in the control group (Wicoxon signed-rank test, p=0.017 for OI,
      p=0.047 for PI, and p=0.037 for PIE group). Before the treatment, GSH-Px
      activities in anemic patients were similar to that of control group (Kruskal
      Wallis test, p>0.05). Although there was no significant decrease in GSH-Px
      activity after OI treatment, both PI and PIE treatments significantly decreased
      GSH-Px activity (Wilcoxon signed-ranks test, p=0.007 for PI and p=0.005 for PIE).
      PIE was more effective than PI treatment in maintaining GSH-PX activity.
      CONCLUSION: Oral iron treatment improved the iron deficiency anemia and recovered
      antioxidant defense system by increasing SOD activity and maintaining GSH-Px
      activity at normal level. When parenteral iron treatment is inevitable, vitamin E
      supplementation together with PI treatment may be effective in partially
      restoring the antioxidant status in this type of anemia.

PMID- 11828553
TI  - Late clinical outcome after radiofrequency catheter ablation of idiopathic
      ventricular tachycardia: follow-up study.
AB  - AIM: To prospectively evaluate long-term clinical outcome in patients who
      underwent radiofrequency catheter ablation for the treatment of idiopathic
      ventricular tachycardia (VT). METHODS: Twenty consecutive patients with
      idiopathic VT resistant to drugs were treated by temperature-controlled
      radiofrequency ablation. The site of VT origin was localized by pace mapping and
      endocardial activation mapping during VT. After ablation, each patient was
      followed up for at least 28 months (median 56, range 28-92). RESULTS:
      Radiofrequency catheter ablation was successful in 15 out of 17 patients with
      idiopathic VT originating from the right ventricle, and in all 3 patients with
      idiopathic VT originating from the left ventricle. The total energy delivered for
      the elimination of VT was higher in patients with idiopathic right VT than in
      those with idiopathic left VT (p=0.014). During the follow-up period, clinical VT
      recurred in 2 patients with unsuccessful ablation. Right and left ventricular
      ejection fractions did not change and were not significantly different at the end
      of follow-up period from those determined before ablation. Also, there was no
      late negative impact of radiofrequency ablation, such as myocardial dysfunction
      or new VT, in any of the patients. CONCLUSION: Initially successful
      radiofrequency catheter ablation of idiopathic VT has excellent long-term results
      without producing late proarrhythmic or cardiodepressant effects. This
      therapeutical procedure is appropriate in cases of idiopathic VT refractory to
      antiarrhythmic drugs.

PMID- 11828554
TI  - Wasp venom is appropriate for immunotherapy of patients with allergic reaction to
      the European hornet sting.
AB  - AIM: To identify whether it is the yellow jacket (Vespula germanica) or European
      hornet (Vespa crabro) venom that induces sensitization in patients with IgE
      mediated allergic reaction to the venom from the sting of a European hornet.
      Since these patients usually have positive skin tests and specific IgE to all
      vespid venoms, it would be useful to distinguish cross-reactors from non-cross
      reactors to perform immunotherapy with the venom that induced the sensitization.
      METHODS: We performed inhibition tests in 24 patients who had experienced
      anaphylactic reaction after being stung by a European hornet. RESULTS: Of 24
      patients with allergic reaction after Vespa crabro sting, 17 were sensitized only
      to epitopes of Vespula germanica venom. Only 4 out of 24 patients were sensitized
      to epitopes completely cross-reactive with Dolichovespula arenaria venom.
      CONCLUSION: In Slovenia, the vast majority of patients with anaphylactic reaction
      to Vespa crabro sting seem to be sensitized to Vespula germanica venom. We
      consider wasp venom an appropriate immunotherapeutic agent for such patients,
      except for those with proven primary sensitization to specific epitopes of Vespa
      crabro venom. Fluorescence enzyme immunoassay inhibition should be considered a
      convenient tool for the identification of primary sensitization in patients
      allergic to vespid venoms.

PMID- 11828556
TI  - Carpal tunnel release by limited palmar incision vs traditional open technique:
      randomized controlled trial.
AB  - AIM: To compare a limited palmar incision for carpal tunnel release (CTR) with a
      traditional open technique, which is still considered the gold standard. METHODS:
      Seventy-two patients with a carpal tunnel syndrome were individually randomized
      into the trial (limited incision CTR) (n=36) and control group (traditional
      technique CTR) (n=36). In the trial group, skin incision parallel to the thenar
      crease was made up to 2.5 cm in length, under an operating microscope and
      endoscopic transillumination. Skin incision in the control group began at the
      distal border of the carpal ligament, followed the longitudinal crease of the
      palm, and crossed the base of the palm in a zigzag fashion. Three months after
      surgery, the patients were asked about symptomatic relief and intervals between
      the operation and return to their daily activities and work, and examined for
      scar tenderness and esthetic outcome. Distal motor latency, conduction velocity,
      scar length, scar width, and operation time were measured. RESULTS: There were no
      differences between the two groups in symptomatic relief and electrophysiological
      parameters. Intervals between the operation and return to daily activities
      (median 5 days, range 2-15) were shorter in the trial group than in the control
      group (median 10 days, range 2-21; p<0.001), as well as the intervals between the
      operation and return to work (median 15 days, range 5-45 vs median 30 days, range
      10-60; p<0.001). Scar/pillar tenderness, scar length and width, esthetic outcome,
      and operation time were significantly better in the trial group. CONCLUSION:
      Limited palmar incision CTR is as effective and safe as traditional CTR
      technique, but with better postoperative recovery and cosmetic results.

PMID- 11828555
TI  - Malondialdehyde, superoxide dismutase, melatonin, iron, copper, and zinc blood
      concentrations in patients with Alzheimer disease: cross-sectional study.
AB  - AIM: To investigate the oxidative stress hypothesis in patients with Alzheimer
      type dementia. METHOD: Serum melatonin, Zn, Cu, Fe, and malondialdehyde (MDA)
      concentrations and erythrocyte superoxide dismutase (SOD) activity were measured
      in patients with Alzheimer disease. Mini-Mental State Examination (MMSE) scores
      were obtained for the patients and their age- and sex-matched healthy controls.
      RESULTS: MMSE score was 16.81.3 in patients with Alzheimer disease, and 28.22.4
      in control group. Melatonin levels were lower in the Alzheimer disease group
      (170.55.2 pg/mL) than in the control group (205.25.8 pg/mL) (p<0.001). Fe, SOD,
      and MDA levels were higher in Alzheimer disease group (131.74.8 microg/dL,
      1,51090 U/g Hb, and 38.14.7 nmol/mL; respectively) than in the control group
      (97.14.1 microg/dL, 1,12050 U/g Hb, and 17.21.6 nmol/mL; respectively) (p<0.001
      for all comparisons). A statistically significant negative correlation between
      melatonin and SOD (r=-0.421, p=0.014) and a positive correlation between age and
      Fe (r=0.325, p=0.049) were found only in the Alzheimer disease group. Correlation
      between age and melatonin was positive (r=0.481, p=0.006) in Alzheimer disease
      group and negative (r=-0.472, p=0.009) in the control group. CONCLUSION:
      Melatonin blood concentration was significantly decreased, and Fe and MDA levels
      were increased in the patients with Alzheimer disease. We believe that low level
      of melatonin, especially if there is a simultaneous increase in Fe level, is
      associated with the development of Alzheimer disease.

PMID- 11828557
TI  - Spinal dysraphism associated with congenital heart disorder in a girl with MELAS
      syndrome and point mutation at mitochondrial DNA nucleotide 3271.
AB  - We describe a case of mitochondrial encephalopathy, lactacidosis, and stroke-like
      episode (MELAS syndrome) associated with ventricular septal defect and
      meningocele at the L3 level in a 5-year-old girl. Mitochondrial DNA analysis
      showed point mutation at nucleotide 3271--> TC. The occurrence of heart and
      neural tube defects in association with usual features of the MELAS syndrome
      might be explained by either defective high-energy metabolism during early
      embryogenesis or a common genetic cause.

PMID- 11828558
TI  - Gastric rupture in a diver due to rapid ascent.
AB  - A 37-year-old, experienced female diver developed gastric rupture due to rapid
      ascent from a depth of 37 meters. The incident was preceded by a heavy meal,
      intake of soda beverages, swallowing of air and water under water, and panic.
      Sharp abdominal pain was present immediately after surfacing and afterwards. Full
      abdominal distension developed within two hours after the ascent. No other diving
      related pathology was found. Surgery was performed around three hours after the
      accident and revealed pneumoperitoneum, gastric rupture, gastric content in the
      abdomen cavity, and signs of acute peritonitis. On surgery, a 4-cm rupture of the
      lesser curvature was found and sutured. The patient was discharged eight days
      after the event.

PMID- 11828559
TI  - Medical education: creating physicians or medical technicians?
AB  - The 20th century witnessed phenomenal growth in scientific medical knowledge and
      technology, enabling physicians to more accurately diagnose and effectively treat
      a wide range of diseases. However, these advances led to longer and more complex
      training periods for physicians and increasing specialization and dependence on
      the new technology. An adverse outcome of these changes has been the development
      of many physicians who are less able to communicate with their patients and deal
      with them in a humanistic and personally caring manner; ie, the development of
      finely trained medical technologists as opposed to caring physicians. Their
      behavior and their blind trust in science and technology without understanding
      the patients in whom illness occurs often leads to making incorrect, incomplete,
      or inappropriate diagnoses or to unnecessary failures of treatment. It also
      results in excessive costs, hazardous procedures, and ill will from patients.
      Unfortunately, such technologically oriented physicians are often the primary
      role models for students. The best hope for a remedy to the problem lies in
      recognizing that it exists, understanding its causes, and modifying medical
      education accordingly. Providing students with good role models and some
      rudimentary techniques can lead to significant gains, but sophisticated programs
      have been designed only in some schools.

PMID- 11828560
TI  - Medical education in Albania: current situation and perspective, with reference
      to primary care.
AB  - A radical primary health care-oriented reform of the medical services in Albania
      is now under way, calling for adequate revision in medical education. The reform
      has started in 1994. In January 1997, the Department of Family Medicine at the
      Faculty of Medicine, University of Tirana, was established for the development of
      general practice and family medicine, and with it a new era in medical education
      in Albania has begun. Mutual agreements for international collaborations are
      being realized, modern medical textbooks are being published, and the importance
      of continuous medical education is gaining a deserved appreciation. Here we
      describe medical education in Albania, including undergraduate education,
      vocational training, and continuing professional development. The emphasis is
      given on primary care, with some suggestions for concrete actions that would
      improve the current situation. A brief descriptive account is given of the
      ongoing Albanian medical education reform, primarily in the field of primary
      health care, which assumes its most interesting global aspects and at the same
      time reflects the unique demands of the country.

PMID- 11828561
TI  - Satisfaction with family medicine training in Turkey: survey of residents.
AB  - AIM: To explore how satisfied family medicine residents are with their training
      in teaching hospitals and current postgraduate training program. METHODS: We
      surveyed 135 family medicine residents in 5 teaching hospitals in Ankara region.
      The residents were asked to fill out the questionnaire at their work place. The
      questionnaire consisted of 23 open- and closed-ended questions about general
      demographic data, training conditions, appropriateness of training, and quality
      of training delivered by clinical teachers in family medicine. The response rate
      was 75%. RESULTS: Seventy percent of respondents found the order of rotation
      important. Most residents were satisfied with the duration of rotation. Eighty
      two percent of residents found basic skills taught during the course of the
      training to be insufficient. Fifty five percent of the participants felt that
      training in teaching hospitals was not sufficient, and majority desired training
      in family practice settings. Ninety-nine respondents suggested establishing a
      coordinating center for family medicine training and training of clinical
      teachers in topics relevant to family practice. CONCLUSION: Family medicine
      residents were generally dissatisfied with their training in major teaching
      hospitals in Turkey. Postgraduate family medicine curriculum needs to be changed
      and opinions of residents regarding their training should be taken into
      consideration.

PMID- 11828562
TI  - Knowledge about and attitude towards science of first year medical students.
AB  - AIM: To assess the knowledge about and attitude towards science of students
      entering medical school, and to find out whether these parameters are influenced
      by their high school education, sex, place of residence, and rank achieved on the
      admission test. METHODS: A total of 193 (82%) students who enrolled at the Zagreb
      University School of Medicine in 2001 filled out an anonymous questionnaire at
      their first lecture. The questionnaire consisted of demographic data, 20
      statements on science adapted to a 1-5 Likert scale, and 8 multiple-choice test
      questions on knowledge of scientific research. RESULTS: The students knowledge of
      scientific research was poor (out of 8 answers, 2.2 +/- 1.2 were correct) in
      spite of their positive attitude towards science (75 +/- 11 on a 20-100 scale).
      Higher ranking students at the admission test showed more positive attitude
      (Spearmans rho=-0.157, p=0.003). There was no interdependence between other
      personal data (sex, high school, and place of residence) and opinion/knowledge
      about science. CONCLUSION: In Croatia, first-year medical students are not
      familiar with basic facts about the scientific methods and communication in
      medicine, but they have positive attitude towards scientific research. The only
      factor associated with more positive attitude towards science is higher rank at
      the admission test.

PMID- 11828563
TI  - Paying tuition and academic performance of students at Kragujevac University
      School of Medicine.
AB  - AIM: To assess whether the prospect of waiving tuition fees influenced the
      academic performance of students with the lowest admission test scores and
      consequent mandatory tuition. METHODS: We compared academic performance of 75
      tuition-paying students with the students who did not have to pay tuition because
      they scored well on the 1996-1998 admission tests to the Kragujevac School of
      Medicine. We formed 3 control groups (high-, medium- and low-ranked students on
      the admission test), each with the similar number of students as the group of
      tuition-paying students. Students performance was assessed after the first two
      academic years on the basis of their average grades, number of tries to pass the
      same examination, the time needed to pass an examination after a course, and the
      number of repeated years. RESULTS: Of 75 tuition-paying students admitted to the
      School in the 1996-1998 period, 11 had their tuition permanently waived and were
      therefore excluded from the analysis after the first year. Tuition-paying
      students had the average grade of 6.8 +/- 3.2 (grade range 6-10), took each exam
      twice before passing it, needed more than four months of studying to pass an
      exam, and repeated 0.1 years per student. Their performance was statistically
      worse than the performance of the low-ranked group of control students in all
      parameters, except in the number of repeated years. The high-, medium-, and low
      ranked student groups did not differ significantly in their performance, but all
      performed significantly better than the tuition-paying group in three following
      parameters: average grade (high-ranked group: 8.2 +/- 1.3), average number of
      tries to pass an exam (high-ranked group: 1.8 +/- 0.8), and average time of
      studying needed to pass an exam (high-ranked group: 119.6 +/- 65.9 days).
      CONCLUSION: The prospect of waiving tuition fees has no influence on students
      performance. The students rank on the admission test is a major predictor of
      their subsequent academic performance.

PMID- 11828564
TI  - Zagreb University School of Medicine: students grades during war.
AB  - AIM: To investigate whether examination grades of the students at the Zagreb
      University School of Medicine changed during the 1991-1995 war in Croatia.
      METHODS: The retrospective descriptive study included examination grades from 5
      major courses in the first 5 years of the medical studies: Anatomy (first year),
      Physiology (second year), Pathology (third year), Internal Medicine (fourth
      year), and Surgery (fifth year). We compared the war-period (1991-1995) with two
      control periods: before (1989-1990) and after the war (1996-2000). The passing
      grades at the Zagreb University range from 2 to 5, with 2 as the lowest and 5 as
      the highest grade. There were a total of 17,682 examinations from the 5 courses
      in the studied periods. RESULTS: Grades were higher in the pre-war and post-war
      periods than in the war period (p<0.001 for both comparisons). Grades in the
      individual courses followed the general trend, except for the surgery course,
      where grades during the war were better than in the control periods, and the
      physiology course, where continual worsening, irrespective of the war, was
      observed. CONCLUSION: Medical students obtained significantly lower grades in 5
      major courses during the war than before or after it. Thus, it is reasonable to
      assume that different factors, some related and some unrelated to war, could have
      adversely influenced students performance.

PMID- 11828565
TI  - Knowledge and attitude regarding sleep medicine of medical students and
      physicians in Split, Croatia.
AB  - AIM: To assess the knowledge and attitudes regarding sleep medicine among second
      year medical students and physicians. METHODS: A total of 112 respondents were
      surveyed for their attitude and knowledge regarding sleep medicine and
      hypertension. The respondents were divided into three groups: 1) second-year
      medical students (46 or 41%); 2) physicians at postgraduate study program (26 or
      23%); and 3) specialists in different fields (40 or 36%). The questionnaire was
      composed of the sleep medicine attitude test, sleep medicine knowledge test, and
      hypertension knowledge test. Differences among the groups were statistically
      analyzed with ANOVA, and differences within each group were analyzed with
      Wilcoxon test. RESULTS: Postgraduate students and specialists showed better
      knowledge in hypertension than in sleep medicine (p=0.001 and p<0.001,
      respectively). In the student group, no difference was found between the
      knowledge in hypertension and sleep medicine (p=0.192). Differences in sleep
      medicine knowledge were not found between medical students and specialists
      (p=0.228) or between postgraduates and specialists (p=0.647). Sleep medicine
      attitude score was similar in all groups (p=0.470). In general, there was a
      positive correlation between sleep medicine knowledge and attitude (p=0.002), and
      between hypertension knowledge and sleep medicine attitude (p=0.019). CONCLUSION:
      Medical students, postgraduate physicians, and specialists showed poor knowledge
      but positive attitude toward sleep medicine. This finding points to the need for
      better education in the field of sleep medicine in medical schools.

PMID- 11828566
TI  - Ethics in medicine: students' opinions on disclosure of true diagnosis.
AB  - AIM: To determine students opinions about diagnosis disclosure to the patient and
      other interested parties. METHODS: During 2000/2001 academic year, an anonymous
      survey was conducted among the first-year (200 questionnaires) and sixth-year
      medical students (200 questionnaires) at the Zagreb University School of
      Medicine. Students were asked what they would say about the diagnosis to the
      patient, patients family, friend, employer, colleague from work, health insurance
      agent, another physician, or medical student, if the diagnosis was inoperable
      lung carcinoma in a 20- and 66-year-old patient vs bacterial pneumonia in
      patients of the same age. The possibilities were to tell the truth, lie, or
      refuse to disclose the diagnosis. RESULTS: The response rate was 55%. Students
      would disclose the true diagnosis to the patient, patients family, friend, and
      employer in case of benign disease more often than in case of malignant disease
      (p<0.001). Patient's age did not affect students' opinions. Most students would
      rather refuse to say anything than lie if they would not want to say the truth.
      Students would more often tell the truth to the patient and patient's family then
      to a health insurance agent, another physician, or medical student, less often to
      patient's friend and employer, and rarely to the patient's colleague from work.
      First-year students would generally tell the truth more often than sixth-year
      students (p<0.001). There were almost no differences in the opinions between male
      and female students. CONCLUSION: The strongest influence on students choice on
      whether or not to disclose the diagnosis had the severity of disease, person they
      would disclose the information to, and the academic year they attended,
      implicating that such important ethical issues should be discussed during the
      studies.

PMID- 11828567
TI  - What do medical students want from their professional and private life?
AB  - AIM: To analyze medical students wishes regarding their professional and private
      life and whether their wishes change over the years of medical studies. METHODS:
      We surveyed 886 of 1,686 students at the Zagreb University School of Medicine
      during the academic year 2000/2001. The students were asked to complete an
      anonymous questionnaire with two groups of 5 wishes, one group pertaining to
      professional and the other to personal life. Students were offered to choose a
      single, most appealing goal they wanted to achieve in private and professional
      life. RESULTS: The predominant categories of professional wishes were for
      humanism and achievement (36%), knowledge (31%), and altruism (22%). Among
      personal wishes, 42% of the students wished for intimacy and love and 38% for
      self-confidence. The frequency of altruistic wishes did not significantly vary
      over the years of study. Women wished more for self-confidence and made more
      altruistic wishes, whereas men preferred influence, friendship, and money.
      Factors, such as the year of studies, average grade, rank at admission test, and
      residence in a large city did not influence the students choices. CONCLUSION: The
      wishes of medical students over the six years of studies proved to be remarkably
      stable and related to personal achievement, knowledge, and altruism.

PMID- 11828568
TI  - Images.

PMID- 11828569
TI  - Understanding and preventing adverse events.

PMID- 11828570
TI  - Harnessing the power of new technologies.
AB  - So far, the human experience comprises about 40,000 years--a period, as the
      historian Arthur Schlesinger points out, of approximately 800 generations. One of
      the most striking realities of our collective experience is that the development
      of what we would consider new technologies has all been essentially within the
      most recent 10 or so generations. Not surprisingly, the speed and scope of
      technological innovation has led to struggles in learning to understand and then
      harness the capabilities we have developed and will continue to develop.

PMID- 11828571
TI  - Educational partnerships: a viable solution to the health care employee shortage.
AB  - It is difficult, if not impossible, to pick up a health care magazine today
      without finding an article concerning the shortage of health care professionals.
      Creative ideas for recruiting new hires, sign on bonuses and employee referral
      programs are commonplace. However, one significant solution is rarely reviewed-
      developing genuine partnerships with educational institutions to assist with
      employee advancement programs.

PMID- 11828572
TI  - A wellness plan for technology.
AB  - Health care organizations are searching for a cure. As organizations merge,
      acquire and struggle to manage costs, many view technology as a panacea. But
      without a full checkup, do they really know what's ailing them?

PMID- 11828573
TI  - Minding your Ps and Qs. Are you measuring up?
AB  - It seems that new sets of hospital quality of care and patient safety measures
      are created monthly. Some of the Joint Commission on the Accreditation of
      Healthcare Organizations measures are similar but different from the Peer Review
      Organization Sixth Scope of Work disease-specific measurement set, which varies
      from the Leapfrog measures, which are not the same as the proposed measures of
      the Michigan Health and Safety Coalition. These are but a few of the dozens of
      measurement sets.

PMID- 11828574
TI  - Planting the seeds of innovation.
AB  - We know the trends--budget cutbacks; shortage of skilled staff; alternative
      medicine; informed and demanding patients; and the increasing cost of medical
      equipment, technology and new drugs. Looking ahead, we know these challenges will
      not disappear. So we have two choices.

PMID- 11828575
TI  - Protecting your domain.
AB  - Trademarks and their sibling service marks are some of the most valuable assets
      of contemporary health care organizations. Patients and health care providers
      throughout the world recognize the name Mayo Clinic. Likewise, pharmaceutical
      companies, particularly with respect to "off-patent" drugs, zealously protect
      drug names.

PMID- 11828576
TI  - It's time for your checkup.
AB  - In 1999, the Institute of Medicine released its report To Err is Human. The
      report estimated the staggering national impact of medical errors and laid out a
      comprehensive strategy to reduce these errors. The report discussed two types of
      errors: errors of execution (a planned action not completed as intended) and
      errors of planning (the wrong plan is used).

PMID- 11828577
TI  - What's really important.
AB  - Sept. 11 caused Americans and Michigan residents to re-evaluate what's really
      important and raised the public's expectations of institutions and elected
      officials. The desire for safety, security and ready access to health services in
      the event of an individual or community emergency vaulted to the top of the
      public's priorities.

PMID- 11828579
TI  - Controlling information technology costs.
AB  - Health care executives are increasingly frustrated by Information Technology
      (IT). Although our industry is often accused of underinvesting in technology
      (hospitals average 2-3 percent of their costs in IT, compared to other industry's
      8-10 percent), when IT investments are made, they fail to reflect demonstrable
      return to the bottom line. Yet the effective deployment of technology is so
      critical to the success of the organization and can in itself cause the failure
      of a health care system.

PMID- 11828580
TI  - Perspectives. Chronic care model: can we get there from here?

PMID- 11828581
TI  - The effect of changes in the U.S. health care system on rehabilitation research:
      the results of a survey of rehabilitation health professionals.
AB  - To obtain empirical data on the impact of changes in the health care system on
      rehabilitation research, physicians, psychologists, nurses, physical therapists,
      and occupational therapists involved in such research were surveyed to determine:
      1) how the changes had affected their research productivity; 2) whether their
      scholarly activities (e.g., publications) had been affected; and 3) whether
      working in an academic vs non-academic institution made a difference. There were
      438 usable responses (38% response rate) to the survey, which was sent to members
      of national organizations. Although the results somewhat supported suggestions
      that changes in the system had had a dampening effect on research, they were
      ambiguous, failing to clearly demonstrate a negative impact of managed care. More
      rigorous study is needed to enable firm conclusions and the formulation of
      actions to address factors that may influence rehabilitation research.

PMID- 11828582
TI  - Integrating evidence-based decision making into allied health curricula.
AB  - An evidence-based approach may decrease variations in practice and time delays in
      adopting new procedures. This report describes the process for incorporating
      evidence-based decision making (EBDM) into curricula using active teaching
      techniques. The process centers on a national four-day Faculty Development
      Institute (FDI) program for dental hygiene, occupational therapy, and physical
      therapy faculty. Phase I assesses pre-Institute EBDM knowledge, skills, and
      teaching strategies. Phase II, onsite, involves learning EBDM principles and
      teaching skills and developing an educational package. Phase III integrates these
      into the curriculum, with ongoing follow-up. At baseline, faculty were unfamiliar
      with EBDM but were incorporating related skills. Formulation of questions and
      evidence gathering for patient-care decisions were weak. Phase II follow-up
      showed a significant increase in EBDM knowledge, p < 0.001, and 100% agreed or
      strongly agreed that they were prepared to integrate EBDM into their courses; 93%
      felt better prepared to use EBDM. Curricula and educational experiences need to
      include EBDM skills. The three-phase process can support faculty in making needed
      changes.

PMID- 11828583
TI  - Evaluation of a post-professional master's program in allied health.
AB  - Changes in allied health education have precipitated a need to review existing
      educational programs. As more disciplines require a graduate degree for
      professional entry, it becomes important to articulate the benefits of advanced,
      post-professional graduate education for allied health professionals. This
      article reports results from a study of one interdisciplinary Master of Health
      Sciences (MHS) program. The intent of the study was to 1) analyze graduates'
      satisfaction with components of the MHS program; 2) explore the perceived impact
      of the MHS program on graduates' professional practices; and 3) examine
      employers' perceptions of the program's effect on graduates' professional
      behaviors. An investigator-developed written questionnaire was used to gather
      perspectives from 53 graduates and 27 of their employers. Graduates believed the
      MHS program had had a positive influence on their employment. Graduates'
      employers concurred, giving high marks to graduates' skill levels and job
      performances. Program graduates were active in professional organizations, but
      few were involved in scholarly activities such as research. Implications for
      curriculum design of advanced master's programs in allied health are discussed.

PMID- 11828584
TI  - Recredentialing in the allied health professions.
AB  - Credentialing of allied health professionals is used to assure the public that
      they are receiving care from competent individuals, and recredentialing is a
      means to demonstrate continuing competence. There is considerable variability in
      the requirements that allied health professions have for recredentialing. Of the
      16 national credentials representing 14 allied health professions that were
      included in this study, 50% had no continuing education (CE) or retesting
      requirement in order to maintain the credential. The remaining 50% required CE in
      amounts ranging from 10 to 50 hours per year, with a mean of 18.5 hours. One
      credential requires both CE and retesting. A review of the literature reveals
      that CE requirements are not linked to improved patient outcomes, and evidence
      linking retesting to improved outcomes is lacking. Therefore, even though there
      is external pressure to implement recredentialing requirements for the allied
      health professions, care needs to be taken to assure that the tools used to
      ensure continued competence are valid and reliable.

PMID- 11828586
TI  - Multiskilling: a course to increase multidisciplinary skills in future dietetics
      professionals.
AB  - Multiskilling, or cross training, can enable students to gain the knowledge and
      skills to become proficient practitioners. This article describes a multiskilling
      course designed to increase dietetics students' awareness of diverse health
      related skills and to enhance their ability to develop new skills for future
      practice. Allied health professionals lectured on and demonstrated
      cardiopulmonary resuscitation, stress management, dysphagia and swallowing
      evaluation, adaptive feeding devices, exercise testing, monitoring of vital
      signs, and multi-department management. Results of course-evaluation surveys
      distributed to the students (n = 12) on the last day were extremely positive,
      with an overall mean rating of 1.07 on a scale of 1 (highest) to 4, indicating
      that the course included appropriate information, assignments, and evaluation
      mechanisms. This study provides preliminary evidence that a didactic experience
      can enhance students' awareness of other allied health professions. Through
      "hands-on" activities, students can become more confident in their knowledge and
      in the skills needed to function effectively as members and leaders of health
      care teams.

PMID- 11828585
TI  - Allied health students' perceptions of and experiences with Internet-based case
      study instruction.
AB  - A challenge for educators is to develop instruction that produces competent
      clinicians and thinkers who are also information-literate. Case-based instruction
      used with the Internet may help. This study examined the experiences of students
      in an advanced cardiopulmonary science course (CPS 1320) that utilized case
      studies placed on the Web. A 29-item online survey was completed by 34 of 39
      allied health science students enrolled in CPS 1320. Four of the 39 were
      interviewed about their experiences with Internet-based case studies. Results
      indicated that placing cases on the Internet assisted students with the practical
      application of theoretical knowledge. Those surveyed expressed a preference for
      Internet-based instruction and indicated that Internet-based case assignments
      were better than traditional lectures for teaching advanced cardiopulmonary
      sciences. However, for many, the approach fostered independent versus
      collaborative work. Also, while increasing access to information, the Internet
      was consumer-focused and distracting. More research is indicated to understand
      how allied health students experience and perceive instruction on the Internet.

PMID- 11828587
TI  - The effects of learning through discussion in a course in occupational therapy: a
      search for deep learning.
AB  - This preliminary educational research study examined occupational therapy
      students' perceptions of the learning through discussion (LTD) method. The study
      incorporated both quantitative and qualitative strategies. A convenience sample
      of nine post-professional occupational therapy doctoral students participated.
      Overall, participating students reported positive experiences when engaging in
      LTD, reporting that they had actively engaged in critical thinking and learning
      and experienced transformative learning. However, the results of nonparametric
      analysis revealed no significant change in the perceptions of the students of
      their classroom performances. Findings are discussed in light of current
      educational programs in occupational therapy. Future research studies are
      recommended to further examine the efficacy of LTD and explore its utility for
      training allied health professionals.

PMID- 11828588
TI  - Hazard report: risk of needlestick injuries from failure of shielded i.v.
      catheters.

PMID- 11828589
TI  - Hazard report: needlestick injury using the Marquest/vital signs PeachCapp
      sliding clip with arterial blood gas syringes.

PMID- 11828590
TI  - Hazard report: staff injuries caused by falling siderail on bariatric
      rehabilitation platform bed supplied by Wheelchairs of Kansas.

PMID- 11828591
TI  - Hazard report: beware of falling equipment.

PMID- 11828592
TI  - Sources of health insurance and characteristics of the uninsured: analysis of the
      March 2001 Current Population Survey.
AB  - This Issue Brief provides summary data on the insured and uninsured populations
      in the nation and in each state. It discusses the characteristics most closely
      related to an individual's health insurance status. Based on EBRI estimates from
      the March 2001 Current Population Survey (CPS), it represents 2000 data--the most
      recent available. Between 1999 and 2000, the percentage of Americans with health
      insurance increased: 84.1 percent of nonelderly Americans were covered by some
      form of health insurance in 2000, up from 83.8 percent in 1999. The percentage of
      nonelderly Americans without health insurance coverage declined from 16.2 percent
      in 1999 to 15.9 percent in 2000, continuing a trend that started between 1998 and
      1999. The main reason for the decline in the number of uninsured Americans was
      the strong economy and low unemployment. Between 1999 and 2000, the percentage of
      nonelderly Americans covered by employment-based health insurance increased from
      66.6 percent to 67.3 percent, continuing a longer-term trend that started between
      1993 and 1994. In 2000, 34.3 million Americans received health insurance from
      public programs, and an additional 16.1 million purchased it directly from an
      insurer. More than 25 million Americans participated in Medicaid or the State
      Children's Health Insurance Program, and 6.1 million received their health
      insurance through the Tricare and CHAMPVA programs and other government programs
      designed to provide coverage for retired military members and their families.
      Even though the number and percentage of uninsured declined substantially between
      1998 and 2000, more than 38 million Americans remain uninsured. While an
      increasing percentage of Americans were being covered by employment-based health
      plans, this trend may not continue because of the combined re-emergence of health
      care cost inflation and the weak economy. As long as the economy is strong and
      unemployment is low, employment-based health insurance coverage will expand and
      the uninsured will decline gradually. However, the combination of the current
      weak economy and the rising cost of providing health benefits will likely result
      in more Americans without health insurance coverage. Should the uninsured remain
      unchanged and continue to represent 15.9 percent of the nonelderly population, 40
      million would be uninsured by 2005. If the uninsured represented 25 percent of
      the population, 63 million would be uninsured in 2005 and 65 million nonelderly
      Americans would be uninsured by 2010.

PMID- 11828593
TI  - Science and technology: new drivers in health care.
AB  - During the next year, Healthcare Leadership and Management Report will intensify
      its coverage of the use of science and technology to improve readiness, and
      financial and operational performance in hospitals and health systems. We will do
      this through a series of case studies from organizations that have had success in
      implementing programs that exploit technology, explaining the nuts and bolts of
      how the success was achieved. Look for a regular science and technology column
      beginning in January.--Lee Reeder, editor.

PMID- 11828594
TI  - Strategies for integrated health care systems.

PMID- 11828595
TI  - E-volving with Rosabeth Moss Kanter. Charismatic Harvard professor raps about the
      new way of working.

PMID- 11828596
TI  - Information therapy: a tale.

PMID- 11828597
TI  - Personalizing medicine on the Web. E-health offers hospitals several strategies
      for success.

PMID- 11828598
TI  - Succeeding at succession planning. Hospitals need to identify their next leaders
      now to ensure smooth transitions.

PMID- 11828599
TI  - A tribute to health care leaders.

PMID- 11828601
TI  - [Forum of carbapenem antibiotics(discussion)].

PMID- 11828600
TI  - Picking up the pieces.

PMID- 11828602
TI  - [Therapies for infectious diseases in the 21st century. The role of minocycline
      among common treatments. Focused on injectable formulation(discussion)].

PMID- 11828603
TI  - [Comparative antibacterial activity of carbapenems against P. aeruginosa (1)].
AB  - Comparative antibacterial activity of imipenem (IPM), panipenem (PAPM), meropenem
      (MEPM) and biapenem (BIPM) was determined against 288 clinical isolates of P.
      aeruginosa collected from various hospitals in 2000. The order of activity by
      comparison of MIC50/MIC80/MIC90 was: MEPM (1/4/8 micrograms/ml) > BIPM (1/4/16
      micrograms/ml) > IPM (2/4/16 micrograms/ml) > PAPM (8/16/32 micrograms/ml).
      Moreover, the order of activity against 75 strains of P. aeruginosa (MIC of CAZ,
      AZT was > or = 16 micrograms/ml and MIC of IPM, MEPM was < or = 8 micrograms/ml)
      by comparison of MIC50/MIC80/MIC90 was: BIPM (1/2/8 micrograms/ml) > or = MEPM
      (1/4/8 micrograms/ml) > or = IPM (2/2/8 micrograms/ml) > PAPM (8/16/16
      micrograms/ml). Judging from both correlation between the MICs of carbapenems and
      relationship between class C beta-lactamase activity and drug susceptibility of
      carbapenems, it becomes apparent that carbapenems, especially BIPM and MEPM will
      be useful for treatment of antipseudomonal cephem resistant pseudomonas
      infection.

PMID- 11828604
TI  - Stats & facts. The gatekeeping question.

PMID- 11828606
TI  - Why aren't we doing more to enhance medication compliance?

PMID- 11828605
TI  - Compliance and refill pattern behavior with HMG-CoA reductase inhibitors after
      acute myocardial infarction.
AB  - Patients who had an acute myocardial infarction or other atherosclerotic event
      and had filled a prescription for an HMG-CoA reductase inhibitor were identified
      for analysis. Compliance was assessed using a multiple-interval refill compliance
      score. The mean compliance score was 80% and six refill patterns were identified.
      Regression analysis revealed three factors associated with compliance: (1) days'
      supply, (2) number of total concomitant medications, and (3) cost sharing.
      Strategies for improving compliance that may have merit include providing
      patients with 60- or 90-day supplies (rather than 30-day supplies), controlling
      the number of other medications prescribed, and lowering copayments for these
      important medications.

PMID- 11828607
TI  - Hand-held wireless devices.

PMID- 11828608
TI  - Health economic considerations in the management of type 2 diabetes.
AB  - The number of therapeutic options for people with type 2 diabetes is increasing.
      Large-scale clinical trials have delineated the health benefits of tight glycemic
      control with these interventions, including the reduction of long-term diabetes
      related complications. These long-term complications compromise quality of life
      and ultimately account for mortality in most patients with diabetes. Despite the
      high price tag of managing the long-term complications of hyperglycemia, few
      economic incentives have been presented for investing in intensive glycemic
      control. Recent cost-benefit analyses, however, provide insight into the major
      cost drivers that yield a short-term return on investment for preventive
      measures. This article highlights cost-effective measures that have been
      successfully utilized in the managed care setting to simultaneously improve
      health and economic outcomes of diabetes within the first few years of
      implementation.

PMID- 11828609
TI  - Preventing nephropathy in patients with type 2 diabetes.

PMID- 11828610
TI  - Alternative medicine networks: build or buy?
AB  - The inclusion of alternative medicine benefits by health plans is on the rise
      nationwide, but how does a health plan decide whether to build its own network or
      to carve one out? The alternative health community has existed largely in
      isolation from orthodox medicine and the evolution of managed care. As such, the
      issues in determining whether to build or buy an alternative medicine network
      differ from some of those related to the other health care specialties that are
      traditionally evaluated for carve-outs.

PMID- 11828611
TI  - Just what the doctor ordered: avoiding kickback pitfalls with prescription drugs.
AB  - Risks associated with the federal antikickback statute increased significantly
      for the pharmaceutical industry in the 1990s. Manufacturers, physicians, and MCOs
      must take account of the statute when developing programs that could possibly
      implicate it. This article provides guidance to the managed care community
      regarding legal kickback risks in arrangements with pharmaceutical manufacturers.

PMID- 11828612
TI  - Glycosidase inhibitors and their chemotherapeutic value, Part 2.
AB  - The various compounds that have been investigated as glycosidase inhibitors are
      reviewed. The second of three parts of this review article covers the following
      classes of compounds: sugars with nitrogen in the ring, e.g. azepine analogues,
      piperidine analogues and pyrrolidine analogues and fused rings with a bridgehead
      nitrogen.

PMID- 11828613
TI  - Importance of the lipophilic group in carbamates having histamine H3-receptor
      antagonist activity.
AB  - In order to evaluate changes in the lipophilic part of designed carbamates
      concerning their potential histamine H3-receptor antagonist properties a new
      series of O-[3-(1H-imidazol-4-yl)propanol]carbamates was derived containing N
      mono- or di-alkenyl, alkynyl, cycloalkyl, or double-branched alkyl substituents.
      The compounds were tested in vitro for their H3-receptor antagonist activity on
      synaptosomes of rat cerebral cortex and shared moderate to high antagonist
      activity in vitro. In this series 3-(1H-imidazol-4-yl)propyl N-(4
      pentenyl)carbamate (4) was the most potent compound in vitro (Ki = 6.3 nM). H3
      receptor antagonist activity in the central nervous system (CNS) was detected for
      most compounds in the in vivo H3-receptor assay based upon measurement of brain N
      tau-methylhistamine levels after p.o. administration to mice. The most effective
      carbamate in vivo, 3-(1H-imidazol-4-yl)propyl N-(allyl)carbamate (3), showed
      higher CNS potency (ED50 = 0.48 mg/kg p.o.) than the reference antagonist
      thioperamide. For some novel carbamates their histamine H1- and H2-receptor
      activities were determined on isolated organs of guinea-pig thereby demonstrating
      their high H3-receptor selectivity.

PMID- 11828614
TI  - New polycyclic azines derived from pyrazolo[3,4-b]pyridine.
AB  - The aminoimidazolinyl derivative 3 was synthesized using the pyrazole amino
      aldehyde 1 as a starting material. Compound 3 has been used as a key intermediate
      in the synthesis of the title compounds.

PMID- 11828615
TI  - Synthesis and antioxidant properties of some new flavone derivatives on lipid
      peroxidation in the rat liver.
AB  - A series of 2'-, 3'-, 4'- and 6-substituted flavone derivatives was synthesized
      and their in vitro effects on rat liver microsomal NADPH-dependent lipid
      peroxidation (LP) levels were determined. Retinoic acid, at 10(-4) M
      concentration, decreased the LP level by about 34%. A significant decrease in
      male liver microsomal LP level was noted for the compounds 3d, 1a, 3b and 4b at a
      concentration of 10(-4) M (100%, 95%, 75% and 62%, respectively).

PMID- 11828616
TI  - Determination of caffeine in pharmaceutical preparations by the linear
      absorbances method.
AB  - In this work a fast Linear Absorbance Method for the determination of caffeine in
      pharmaceutical preparations in the presence of paracetamol or acetylsalicylic
      acid is presented. The determination of acetylsalicylic acid or paracetamol is
      also possible by means of a tabulated parameter fB, which values are included in
      this paper. The method avoids the use of separation steps or multicalibration
      methods. The determination was carried out in commercial preparations with good
      results.

PMID- 11828617
TI  - Urinary metabolites of French maritime pine bark extract in humans.
AB  - After oral administration of 5.28 g and 1.06 g of French maritime pine bark
      extract to a human volunteer, metabolites of some of the components of the
      extract could be detected. Ferulic acid and taxifolin, conjugated as
      glucuronide/sulphate, were excreted within 18 h. The peak urinary excretion was
      observed approximately 2-3 h after intake. Recovery of ferulic acid in urine was
      36-43% and 7-8% for taxifolin. Two further metabolites could be identified as
      delta-(3,4-dihydroxy-phenyl)-gamma-valerolactone and delta-(3-methoxy-4
      hydroxyphenyl)-gamma-valerolactone conjugated with glucuronic acid/sulphate.
      These metabolites could also be detected after intake of 960 mg of a procyanidin
      fraction of French maritime pine bark extract. Thus, it was shown that
      procyanidins are metabolised by humans. Both metabolites show maximal urinary
      excretion 8-12 h after intake and are excreted within 28-34 h.

PMID- 11828618
TI  - Lipophilic metronidazole derivatives and their absorption through hairless mouse
      skin.
AB  - Previously we have shown that the diacyl glyceryl ester of naproxen is absorbed
      into excised mouse skin and slowly degraded to release naproxen. In the present
      work we have synthesised some organic acid and fatty acid derivatives of
      metronidazole, and studied the in-vitro degradation in aqueous buffer solutions
      and serum as well as their permeation through hairless mouse skin. The
      derivatives were enzymatically degraded in serum to form metronidazole. Only the
      acetic acid and butyric acid derivatives were able to permeate hairless mouse
      skin intact. The fatty acid derivatives released metronidazole within the skin.
      The metronidazole delivery through the skin was significant when the
      metronidazole oleate was used. This compound could therefore be considered as a
      suitable pro drug for dermal applications.

PMID- 11828619
TI  - Effect of drug solubility on the in vitro availability rate from suppositories
      with lipophilic excipients.
AB  - The factors involved in mechanisms of availability of different drugs from
      suppositories with lipophilic excipients were studied by using an in vitro model
      of the rectal compartment with a porous membrane simulating the rectal barrier.
      The solubility in water of drugs was found to be the fundamental factor
      influencing the release rate from suppositories. In fact, following the melting
      of the suppository at body temperature the drug particles can migrate to the
      interface with the small volume of rectal secretion where they dissolve. Drug
      molecules can so diffuse until they come into contact with the rectal barrier
      through which the drug is absorbed. Drug concentration in the intrarectal aqueous
      phase produces the gradient against the large volume of the plasma phase. This
      gradient regulates the diffusion rate through the barrier. A drug with a low
      water solubility saturates the intrarectal phase at low concentration hindering
      the subsequent dissolution of the drug particles remaining in the melted
      excipient. This fact maintains the viscosity of the melted suppository at a ligh
      level, which slows the migration of the particles. On the other hand, a drug with
      high water solubility quickly leaves the excipient, producing a high
      concentration in the intrarectal phase which supports a high diffusion rate
      across the barrier. The results obtained indicate that drugs with low solubility
      in water result in low availability, while drugs with good solubility can give an
      intense and rapid drug supply for a rapid and intense therapeutic response with
      the dose administered almost completely utilised.

PMID- 11828620
TI  - Dextrin as excipient in pharmaceutical preparations.
AB  - The addition of commercial dextrins to aqueous solvents in thin layer
      chromatography on cellulose increases the Rf values of azodyes such as methyl
      orange. The increase is less than with cyclodextrins but shows that dextrins also
      form supramolecular complexes. This should be considered when dextrins are used
      as "inert" excipients in pharmacy.

PMID- 11828621
TI  - Effect of Australian tea tree oil on the viability of the wall-less bacterium
      Mycoplasma pneumoniae.
AB  - In vitro assays using a variety of essential oils revealed a particularly high
      antibacterial effect of Australian tea tree oil (TTO) on a great number of gram
      negative and gram-positive bacteria of unrelated phylogenetic origin. In the
      present study, the susceptibility of cell wall-less bacteria such as the human
      pathogenic bacterium Mycoplasma pneumoniae to Australian tea tree oil was
      examined. The minimum inhibitory concentration (MIC) was determined to be 0.006%
      (v/v) TTO for the wild type and to 0.003% (v/v) TTO for mutants of M. pneumoniae
      which lost the ability to adhere to host cells (cytadherence-negative). The MIC
      and the MBC (minimum bactericidal concentration) for M. pneumoniae are 100 times
      lower than those for all other eubacteria tested. Electron microscopy with
      negatively stained cells as well as with ultrathin sections revealed a tendency
      to ovoid or round cells after oil treatment whereas the untreated cells of the
      wild type exhibit a flask-shaped morphology with a tip-like structure at one pole
      of the cell. The integrity of the mycoplasmal membrane seems not to be affected
      by TTO since no leakage of the Mycoplasma cell was observed after oil treatment.
      In the HET-CAM test TTO did not show any visible signs of irritation in
      concentrations less than 25%. Although the active component in TTO that has anti
      mycoplasmal activity is not known, it seems very promising to use TTO tentatively
      for mouth washing and inhalation in case of Mycoplasma-pneumoniae-infection.

PMID- 11828622
TI  - New ursane-type triterpenic esters from the stem bark of Thevetia peruviana.
AB  - Phytochemical studies on the stem bark of Thevetia peruviana resulted in the
      isolation of six new ursane-type triterpenes, named peruvianursenyl acetate A,
      peruvianursenyl acetate B, isolupenyl acetate, peruvianursenyl acetate C,
      lupedienyl acetate and peruvianursenyl glucoside along with two known
      triterpenoids, namely alpha-amyrin acetate and lupeol acetate. The structures of
      the new phytoconstituents have been established as 23--nor methyl urs-12-en-4
      alpha-ethylenic-18 alpha-H-3 beta-yl acetate, urs-5.21-dien-18 alpha-H-3 beta-yl
      acetate, lup-20 (29)-en-3 alpha-yl acetate, urs-12 en-18 alpha-H-3 beta-yl
      acetate, lup-5,20 (29)-dien-3 beta-yl acetate, and urs-12-en-18 alpha-H-3-O-beta
      D-glucopyranoside, respectively.

PMID- 11828623
TI  - Kinetics of thermal decomposition of talampicillin hydrochloride in the solid
      state.

PMID- 11828624
TI  - HPLC identification and determination of flavone aglycones in Helichrysum
      plicatum DC. (Asteraceae).

PMID- 11828625
TI  - Separation of (R,S)-mexiletine by capillary zone electrophoresis and preparative
      resolution of mexiletine racemate with (R)- or (S)-mandelic acid.

PMID- 11828626
TI  - Mathematical evaluation of the dissolution of metronidazole from tablets.

PMID- 11828627
TI  - Poikilothermia induced by a 2-furancarboxylic acid derivative.

PMID- 11828628
TI  - Xanthohypericoside, a new xanthone-O-glucoside from Hypericum annulatum.

PMID- 11828629
TI  - [Diagnosing dementia is very difficult].

PMID- 11828630
TI  - [The intention to treat].

PMID- 11828632
TI  - [Glaucomas].
AB  - Glaucoma is a chronic optic neuropathy related to progressive loss of visual
      fibers. It can lead to complete blindness. There are several types of glaucoma:
      primitive open angle glaucomas, angle closure glaucomas, secondary glaucomas and
      congenital glaucomas. The diagnosis of the disease relies on the alterations of
      the visual field, the measure of intraocular pressure, the aspects of the optic
      disc and of the iridocorneal angle. As most of the glaucomas are asymptomatic,
      they often induce a severe loss of vision. Therefore, its systematic screening by
      ophthalmologists is mandatory.

PMID- 11828631
TI  - [Anatomy, physiology, and functional exploration of the optic nerve].
AB  - Disturbances of the optic nerve make up a large part of neuro-ophthalmology. They
      consist in large part of glaucoma and toxic inflammation of the optic nerve
      (retro-bulbar optic neuropathy). Progress in the understanding of the function of
      ganglion cells, in particular the discovery of the M and P pathways, comprise a
      considerable advance in the comprehension of the optic system as a whole.
      Progress in techniques of studying the visual field, the ERG pattern and imaging
      of the pupil have an influence on the diagnosis, the follow-up and the initiation
      of new therapeutic strategies in glaucoma and disorders of the SEP.

PMID- 11828633
TI  - [Treatment of glaucomas].
AB  - Glaucomas have to be considered as the final common pathway of various diseases
      rather than a single disease. Therefore treating glaucomas remains a difficult
      task since the clinical presentations of the glaucomas are very different without
      any definite known cause; only some risk factors are believed to lead to the
      glaucomas. Among these risk factors intraocular pressure is really possible to
      treat and focuses all our therapeutic attempts. The general practitioner and the
      ophthalmologist have to work close together to better evaluate the systemic
      adverse effects of topical medications and to avoid harmful drugs for the outcome
      of the glaucomas.

PMID- 11828634
TI  - [Acute anterior, ischemic optic neuropathy].
AB  - Ischemic optic neuropathy (ION) is the most frequent optic neuropathy in patients
      older than 50. Anterior ION is classified as nonarteritic, especially in patients
      with vasculopathic risk factors and/or small optic disc, or arteritic. Monocular
      visual loss is usually sudden. Typical exam findings are optic nerve swelling and
      altitudinal visual field defect. Clinical profile, sedimentation rate, and
      especially fluorescein angiography are very useful to make the distinction
      between nonarteritic and arteritic ION. Treatment of temporal arteritis with
      steroids is an emergency but there is no effective therapy of the nonarteritic
      form.

PMID- 11828635
TI  - [Inflammatory optic neuropathies].
AB  - Diagnosis of inflammatory optic neuropathy is very likely in a young adult
      presenting acute, unilateral and painful visual loss. Relative afferent pupillary
      defect is a very sensitive and specific sign of optic neuropathy.
      Ophthalmological exam is mandatory to estimate severity of visual loss,
      appearance of optic disks and check for another eye disease. Magnetic resonance
      imaging is indicated to rule out a compressive optic neuropathy and to quantify
      the inflammatory lesion index, which is the best prognostic indicator of multiple
      sclerosis development (MRI is abnormal at entry in about 50% of patients with
      isolated optic neuritis). Spontaneous outcome of optic neuropathies is
      favourable. Corticosteroids have demonstrated efficacy only in shortening length
      of evolution and by using parenteral high doses. Clinical benefit from
      introducing beta-interferons treatment after a first episode of isolated optic
      neuritis remains to be evaluated. Secondary inflammatory optic neuritis
      (infection, vasculitis, sarcoidosis) are rare and usually present atypical
      evolution or other symptoms.

PMID- 11828636
TI  - [Papilledema and intracranial hypertension].
AB  - Isolated bilateral papilloedema require magnetic resonance imaging (MRI), looking
      for tumor, hydrocephalus, cerebral venous thrombosis. If MRI is normal and
      doesn't show any risk for tonsillar herniation, lumbar puncture has to be done
      with cerebrospinal fluid (CSF) pressure evaluation. Intracranial hypertension
      without any intracranial lesion (mass lesion, arteriovenous shunt, venous
      thrombosis) is Pseudotumour Cerebri Syndrome. Risk of such Pseudotumour Cerebri
      is progressive blindness. Treatment cures intracranial hypertension and stops
      visual defect.

PMID- 11828637
TI  - [Nutritional, toxic and drug-induced optic neuropathies].
AB  - Painless, bilateral, insidious loss of central vision associated with
      dyschromatopsia should alert the physician to the possibility of a nutritional,
      toxic or iatrogenic optic neuropathy, sharing similar clinical features. Given
      the increasing number of available drugs for systemic disorders, a variety of
      newly introduced medications have been related to toxicity on the optic nerve.
      Detecting the cause in the early stages of the disease is mandatory, as
      withdrawal of the toxic agent may result in vision recovery.

PMID- 11828638
TI  - [Leber's optic neuropathy].
AB  - Leber hereditary optic neuropathy is associated to mutations of the mitochondrial
      DNA that seem to be pathogenic of this disease. However, other genetic or
      environmental factors must play a role in the development of this optic atrophy.
      Leber hereditary optic neuropathy is usually isolated. Its typical clinical
      feature includes in a young man a sudden and severe decrease of vision of one
      eye. The second eye is affected few weeks later. But, atypical feature can be
      observed. Thus, this diagnosis must be suspected as soon as there is no evident
      aetiology for an optic neuropathy, whatever the clinical feature, the age or the
      sex of the patient can be. There is no treatment. But visual recovery can
      spontaneously occurred even years after the disease appearance.

PMID- 11828639
TI  - [Evaluating the stages].

PMID- 11828640
TI  - [Chronic lymphoid leukemia].

PMID- 11828641
TI  - [Broncho-pulmonary infections of infants and children].

PMID- 11828642
TI  - [Muco-cutaneous allergies in children and adults. Urticaria. Atopic and contact
      dermatitis].

PMID- 11828643
TI  - [Genital infections of women. Leukorrhea].

PMID- 11828644
TI  - [Algodystrophy].

PMID- 11828645
TI  - [Cirrhosis and complications].

PMID- 11828646
TI  - Treating patients abroad. Worlds apart.
AB  - The government is making a virtue out of necessity by letting the NHS use spare
      capacity on the continent to help clear waiting lists. Better-educated and
      informed patients are likely to benefit most. The move will encourage comparisons
      between health services in the UK and other European countries, even if take-up
      is limited.

PMID- 11828647
TI  - First person. Anything for a quiet life.

PMID- 11828648
TI  - Primary care trusts. In the know.
AB  - PCTs allow a strategic approach to primary care research that supports
      collaboration between professionals and practices and reflects local and national
      priorities. The implementation of a research strategy in one PCT provides a
      useful working model.

PMID- 11828649
TI  - Wait watcher. Blank checks.

PMID- 11828650
TI  - Primary care trusts. Called to account.
AB  - Primary care trusts are set to control three-quarters of the NHS budget. Many
      will be hindered in their new roles by inexperienced managers, unproven processes
      and fledgling support systems. Workforce planning and the appointment of
      dedicated project managers to drive change is an urgent priority.

PMID- 11828652
TI  - PCTs/risk management. Control tweakery.

PMID- 11828651
TI  - PCTs/health improvement. The object of the exercise.
AB  - A study of six primary care trusts showed that those most successful in tackling
      health improvement had certain common characteristics. Strong board-level support
      and leadership, combined with development funding, were the most effective.
      Successful PCTs also showed a corporate recognition of local health and socio
      economic inequalities.

PMID- 11828653
TI  - Why can't we all get along? Building better relationships.

PMID- 11828654
TI  - Compulsive comparing.

PMID- 11828655
TI  - 2002-2003 long-term care standards.

PMID- 11828656
TI  - [The truth about devitalization].

PMID- 11828657
TI  - [Devitalization--a challenge or a resolved marginal matter].

PMID- 11828658
TI  - [Mediastinal teratomas in children].
AB  - The objective of the work is a clinical and histopathological retrospective study
      of rare mediastinal teratomas in children. The authors present their experience
      with the treatment of eight children within the range from neonates to the age of
      15 years with a histologically confirmed diagnosis of mediastinal teratoma. In
      two neonates the first symptom was postnatal dypnoea, teratomas in older children
      were diagnosed along with symptoms of acute respiratory infection. Complete
      resection of the tumor was performed in all patients, in neonates emergency
      operations were involved. Four tumors were histologically classified as mature
      teratomas, three as differentiated teratomas with an immature component and one
      as a malignant teratoma. The malignant teratoma contained mature tissues as well
      as tissues of embryonic carcinoma and a yolk sac tumor. Seven children with a
      mature or differentiated teratoma are without signs of disease 5-15 years after
      surgery. During the follow-up of the 15-year-old boy with the malignant teratoma
      the elevated alpha-fetoprotein serum level was evidence of a relapse of the
      disease after termination of comprehensive treatment. From the results ensues
      that radical extirpation is sufficient treatment for mature and differentiated
      teratomas. Malignant teratomas are indicated for primary resection and
      postoperative chemotherapy. Long-term follow up of alpha-fetoprotein and human
      beta-choriogonadotropin levels, clinical controls and controls by imaging methods
      are indicated in children with an immature or malignant component of the tumor.

PMID- 11828659
TI  - [Reconstruction of the diaphragm with a polytetrafluoroethylene patch in neonates
      with congenital diaphragmatic hernia].
AB  - The authors present their experience with the reconstruction of the diaphragm
      with a synthetic polytetrafluoroethylene patch in a group of 66 neonates with a
      congenital diaphragmatic hernia. After preoperative stabilization 53 neonates
      (80%) were operated, simple reconstruction of the diaphragm was made in 39
      neonates (74%), reconstruction of the diaphragm with a polytetrafluoroethylene
      patch was indicated in 14 patients (26%). Nine patients recovered after
      reconstruction of the diaphragm by a synthetic patch without complications. The
      only relapse of diaphragmatic hernia when using a patch was recorded in a neonate
      with a bilateral diaphragmatic hernia, sternal cleft and omphalocele. After
      simple reconstruction of the diaphragm there was no relapse of hernia. The total
      mortality in the group was 27% (18 neonates). After surgery five neonates died.
      Two of them died of serious haemorrhagic complications during extracorporeal
      membrane oxygenation and three died after operations performed at borderline
      oxygenation and ventilation values and subsequent deterioration of the general
      condition. In four of them a polytetrafluoroethylene patch (GORE-TEX) was used.
      Reconstruction of the diaphragm by a polytetrafluoroethylene patch is a suitable
      surgical method in the treatment of neonates with a congenital diaphragmatic
      hernia. Indication for the use of a patch is agenesis of the diaphragm and major
      diaphragmatic defects with hypoplastic borders. The use of a non-absorbable
      synthetic patch is from the aspect of the long-term effect on growth and the
      development of skeletal deformities equivocal and will call for further detailed
      studies.

PMID- 11828660
TI  - [Injuries of the cervical spine in children--2 case reports].
AB  - Helical CT of the spine was done for suspicion of injury in 22 children (from
      July 1999 to December 2000): cervical spine in 7 children (average age 12.1
      years), thoracic spine in 10 children (average age 11.9 years), lumbar spine in 5
      children (average age 14.6 years). MR examination were done in 23 children:
      cervical spine in 3 children (average age 7.5 years), thoracic spine in 16
      children (average age 10.5 years), lumbar spine in 4 children (average age 13.3
      years). (There were no differences between the distribution of boys and girls in
      thoracic spine injuries; in cervical and lumbar spine injuries girls
      predominate). 2 case reports are described.

PMID- 11828661
TI  - [Use of central venous catheters in children with hematologic neoplasms from the
      viewpoint of the pediatric surgeon].
AB  - Venous access by cannulation of the central vein is a necessary prerequisite of
      the oncological treatment. Within the period 1998-2001 there 395 CVCs (Central
      Venous Catheters) were introduced using a subcutaneous tunnel in 335 hospitalised
      patients at the Clinic of the Child Surgery, Orthopaedics and Traumatology FN
      Brno. In 310 patients Hickman CVC was used and in 25 Groshong CVC. Using the vena
      subclavia 1. dx., 131 CVCs were introduced, via the vena subclavia 1. sin. 264
      CVCs. The average period of CVCs introduction was 3 months. In 78 introduced CVCs
      infectious complication developed. A local infection was noticed only 8 times,
      general infection at 70 cases. In 13 patients CVCs had to be removed. The authors
      present their experience with the introduction of tunneled CVCs in oncological
      patients and the options for solving the infectious complications when using
      CVCs.

PMID- 11828662
TI  - [Acute cholecystitis during the time of minimally invasive abdominal surgery] ].
AB  - OBJECTIVE: To define optimal rules for the treatment of acute cholecystitis
      taking into account possible laparoscopic surgery. METHOD: Critical analysis of
      the authors' group of 90 patients with acute cholecystitis. RESULTS: Optimal
      results were achieved with surgical treatment within 72 hours after the first
      clinical symptoms of the disease without the need of conversion of the
      laparoscopic operation in the authors' group. Surgery between the third and tenth
      day of hospitalization is unfavourable with a conversion rate of 18%. CONCLUSION:
      Acute cholecystitis with complications calls for urgent classical surgery, acute
      cholecystitis without complications laparoscopic operation within 72 hours after
      the first clinical symptoms. In critically ill patients alternative
      cholecystostomy or puncture of the gallbladder may be used.

PMID- 11828663
TI  - [Recurrent adhesive ileus after surgical treatment of ovarian teratoma,
      malposition of an intrauterine device and dolichosigmoid--case report] ].
AB  - A 30-year-old woman was operated for ovarian teratoma and repeatedly for adhesive
      ileus during 1995-1999. A partial left ovarectomy, extirpation of an intrauterine
      device (IUD) in malposition (greater omentum) and appendectomy were performed
      during the first operation. Early adhesive ileus developed on the fourth
      postoperative day. Adhesectomy was performed in the region of the terminal
      jejunum. A new adhesive ileus developed after twenty seven months when patient
      underwent laparoscopy for gynaecological problems with conversion to laparotomy
      because of greater adhesions intraperitoneally another adhesectomy was performed.
      During the next eleven months new adhesive obstructions of the bowel developed
      and a third operation had to be performed incl. resection of the
      dolichosigmoideum on account of chronic problems during defaecation. A special
      tube as a intraluminal splint was inserted as prophylaxis of mechanical ileus in
      the postoperative period. But during next thirteen months subileous conditions
      and mechanical ileus developed again (up to now). The picture of intraperitoneal
      conditions was disastrous: almost total fibrotic changes allowed only partial
      adhesectomy. The passage through bowel is limited and is restricted to dietetic
      and medicamentous preparations. This case-report demonstrates postoperative
      adhesions a very old and very serious problem at the beginning of the third
      millennium.

PMID- 11828664
TI  - [Incidence of carcinomas in goiters and their combination with Hashimoto's
      thyroiditis].
AB  - In the investigated group 300 patients were operated for a thyropathy mostly
      struma nodosa, tumours were proved in 69 cases; 38 of them were carcinomas of
      various extent and 3 of them were combined with Hashinoto's lymphomatous goitre.
      The overwhelming majority of the carcinomas were papillary carcinomas (22 cases).
      The incidence of papillary carcinoma in Hashimoto's goitre was about 8%; this
      fact calls for more attention to autoaggressive thyroiditis both in examination
      of surgical material, and during autopsies in middle-aged women, where this
      thyroiditis is often clinically silent. Our results suggest an increase in the
      incidence of carcinoma in Hashimoto's goitre and the generally accepted rarity of
      this coincidence is questioned. We recorded also a lower incidence of medullary
      carcinoma than the worldwide average and a more frequent incidence of mixed-type
      carcinoma.

PMID- 11828665
TI  - [Fractures of the calcaneus].
AB  - The authors present the results of another investigation of a group of casualties
      with fractures of the calcaneum treated by open reposition and stabilization with
      a splint and screws in 1994 to 1996, followed up after an interval of 57-74
      months after the injury, on average after 66 months. Sixteen patients (20
      calcanea) could be followed up, 7 patients were lost (8 calcanea). Again two
      evaluation patterns were compared. According to the authors the results were
      evaluated 12x as excellent, 6x as good and 2x as poor. On subjective evaluation
      13 patients were satisfied, another three satisfied with reservations. During the
      subsequent follow up no complications developed. In all patients the
      osteosynthetic material was extracted and in one also ossificates in the planta.
      In two patients spontaneous talocalcaneal fusion occurred. Since 1997 in the
      Casualty Hospital as the basic method for treatment of dislocated intraarticular
      fractures of the calcaneum ligamentotaxis by exterior fixation is used (the
      authors give an account of all therapeutic methods used between 1994 and 2000).
      The authors evaluated a group of 28 casualties (36 fractures of the calcaneum)
      treated by external fixation, 18-81 months after injury, on average after 34.3
      months. The evaluation proceeded in the same way. According to the authors'
      pattern the result was excellent 8x, good 13x and poor 15x. Spontaneous
      talocalcaneal fusion occurred 9x, 2x desis was performed and 1 desis is planned.
      As to subjective evaluation, 11 patients were satisfied, 15 were satisfied with
      reservations and two were not satisfied. According to the authors' opinion to
      achieve reposition of fragments of a fractured calcaneum in addition to other
      possibilities open reposition and synthesis using screws (possibly plate and
      screws) remains the basic method.

PMID- 11828666
TI  - [Classical versus laparoscopic plasty of inguinal hernias].
AB  - Operations of hernias in groin area are frequent. They account for 7-10% of all
      operations in surgical departments. The surgical solution of inguinal hernias is
      not simple. There exist many correction techniques. At present there is moreover
      a laparoscopic approach. The aim of the present study was to compare the results
      of inguinal hernias operated using conventional and laparoscopic techniques on
      the surgical department of the Pardubice Hospital during 1997-1998. We focused
      attention on the incidence of peroperative and postoperative complications and
      reconvalescence period.

PMID- 11828667
TI  - [We have nothing to be ashamed of].

PMID- 11828668
TI  - The making of a miracle.

PMID- 11828669
TI  - Oh, the possibilities.... Understanding e-commerce to exercise its full
      potential.

PMID- 11828670
TI  - Worth the push. An ergonomics programs can save time and money.

PMID- 11828671
TI  - Staying power. Incentives can help retain workers.

PMID- 11828672
TI  - Breeding ground for growth.

PMID- 11828673
TI  - Developing a master plan.

PMID- 11828674
TI  - The facts about the liability crisis.

PMID- 11828676
TI  - Dietary intakes and leisure-time physical activity in West Virginians.
AB  - Poor diet and physical inactivity contribute to many chronic diseases in the
      United States each year. Diets low in saturated fatty acids and cholesterol and
      high in plant foods, i.e., fruits and vegetables, legumes and whole cereals, are
      protective. Physically active lifestyles are associated with lower risk of
      cardiovascular diseases, diabetes, obesity and some cancers. To access diet and
      physical activity levels in West Virginians, we conducted a study which was
      supported by the West Virginia Bureau for Public Health and the West Virginia
      University Prevention Research Center (CDC Cooperative Agreement). The purposes
      of this study were to estimate the proportion of the sample meeting
      recommendations for chronic disease prevention, and to examine if the individuals
      who were meeting the Surgeon General's physical activity recommendation for
      health are also consuming healthier diets. Our results showed that reducing
      saturated fatty acids and increasing consumption of folate, Vitamin E, calcium
      and fiber are of prime public health importance in West Virginia. Diet and
      activity levels were modestly related, suggesting that those who adopt a healthy
      diet also become more active and vice versa. Due to the cross-sectional nature of
      this data, it is unknown if single-strategy or dual interventions work best.
      Prospective studies are needed to determine optimal strategies.

PMID- 11828675
TI  - Persantine improves acute pancreatitis in vitro.
AB  - Persantine combined with TNF-a enhances antiproliferative activity in human tumor
      cells. We hypothesized that the vasodilator persantine would ameliorate acute
      pancreatitis (AP) in vitro. Rat pancreatic ductal cells were cultured using
      standard techniques. Acute pancreatitis was induced by adding cerulein (10(-9) M)
      or TNF-a (200 ng/ml). AP was verified by increased amylase production. Persantine
      was added at concentrations from 0.1 uM to 100 uM post cerulein or TNF-a
      treatment. Statistical analysis was achieved by ANOVA. Amylase production was
      significantly increased (p < 0.05) compared with control upon stimulation with
      either cerulein or TNF-a. When persantine was added in graded concentrations from
      0.1 uM to 100 uM to cerulein treated cells, it decreased amylase production
      significantly (p < 0.05) at 100 uM. However, when persantine was added to TNF-a
      treated cells, it decreased amylase production (p < 0.05) at the lower
      concentrations of 0.1 uM and 1 uM. We have shown for the first time that AP,
      resulting from either mild (cerulein) or severe (TNF-a) stimulation, is
      significantly improved by treatment with persantine.

PMID- 11828677
TI  - The clinical entity of remitting seronegative synovitis with pitting edema (RS3PE
      syndrome).
AB  - Remitting seronegative symmetrical synovitis with pitting edema is a clinical
      entity distinct from polymyalgia rheumatica arthritis appearing in elderly
      patients. Distal pitting edema and tenosynovitis of the digitorum tendons are
      characteristically seen in this disorder. In contrast to polymyalgia rheumatica
      and rheumatoid arthritis, treatment with low-dose glucocorticoids usually
      produces a prompt and enduring remission after several months. Follow-up
      evaluations are necessary not only to assure this diagnosis is posterior, but
      also to observe for the possible occurrence of associated neoplasms.

PMID- 11828678
TI  - Patient-centered medicine: achieving outcomes in end-of-life care that will meet
      with high patient and family satisfaction.

PMID- 11828679
TI  - Building a new health care system.

PMID- 11828681
TI  - Focused residency training key to future of specialty.

PMID- 11828680
TI  - Coding & documentation: no harder than biochemistry.

PMID- 11828682
TI  - CPT: what's new in 2002?

PMID- 11828683
TI  - Toward sensitive treatment of obese patients.

PMID- 11828684
TI  - "You should see my doctor": cost-effective marketing ideas for your practice.

PMID- 11828685
TI  - Tuning up your patient schedule.

PMID- 11828687
TI  - Looking for a good electronic medical records system?

PMID- 11828686
TI  - Race and preventive services delivery.

PMID- 11828688
TI  - Stem cells. What clones? Widespread scientific doubts greet word of the first
      human embryo clones.

PMID- 11828689
TI  - Chemistry. Paving out pollution.

PMID- 11828690
TI  - Medical geology. Coal control.

PMID- 11828691
TI  - Medicine. Count to 10. Frog eggs may crack the mystery of how anesthesia works.

PMID- 11828692
TI  - Aviation. Quieting killer wakes.

PMID- 11828693
TI  - Physics. Setback for Super-K. Disaster blinds the world's leading neutrino
      detector.

PMID- 11828694
TI  - Acoustics. Sonic womb.

PMID- 11828695
TI  - Assembling the future. How international migrants are shaping the 21st century.

PMID- 11828696
TI  - Down with the bad, up with the good. A biotech firm develops a vaccine to raise
      good cholesterol levels.

PMID- 11828697
TI  - Intellectual improprieties. A leading gadfly picks some of the worst patents of
      all time.

PMID- 11828698
TI  - The gradual illumination of the mind.

PMID- 11828699
TI  - The network in every room.

PMID- 11828700
TI  - The magic of microarrays.

PMID- 11828701
TI  - Madagascar's mesozoic secrets.

PMID- 11828702
TI  - Bejeweled worlds.

PMID- 11828704
TI  - Eye in the sky.

PMID- 11828705
TI  - Surrounded by sound.

PMID- 11828703
TI  - Television addiction is no mere metaphor.

PMID- 11828706
TI  - [Guideline of antibiotics usage in surgical fields].

PMID- 11828707
TI  - [A guide line for antibiotic therapy of infectious diseases of the central
      nervous system].
AB  - The purpose of this paper is to provide assistance to clinicians in the treatment
      of infectious diseases of the central nervous system. Antibiotic therapy should
      be initiated as soon as the diagnosis is made and should not be delayed until the
      next scheduled dose or until investigations have been performed. The infecting
      organism is usually unknown when treatment is initiated and often remains so, and
      therefore empirical therapy should always cover the most common suspected
      organisms. The choice of antibiotics, dosage, and route of administration depends
      upon the severity of illness. Likely pathogens and the known sensitivities of
      pathogens of the central nervous system are discussed.

PMID- 11828708
TI  - [Guideline of antimicrobial therapy in the area of cardiovascular surgery].
AB  - Although cardiovascular surgery is considered to be aseptic, prolonged hospital
      stay before and after surgery, the use of artificial materials and
      cardiopulmonary bypass, long-term use of intratracheal tubes or intravenous
      catheters, and an increase in surgeries on high-risk patients increase the
      incidence of postoperative infections. Therefore meticulous management to
      minimize bacterial contamination before and after surgery and identification of
      patient risk factors are important to reduce their incidence and severity, in
      addition to optimal antimicrobial therapy. As the targets of prophylactic
      antibiotics are usually superficial and environmental bacteria, those of choice
      are first or second-generation cephalosporins or penicillin with sulbactam. If
      postoperative infection is suspected, identification of the infectious site and
      pathogens and their susceptibility to anitimicrobials is useful to control
      infections. The use of broad-spectrum antibiotics is not recommended because
      these drugs induce bacterial resistance to antibiotics. Infectious endocarditis
      (IE) and deep wound infections, such as mediastinitis, are major serious
      infections after cardiovascular surgery. Antibiotics should be selected by
      considering the susceptibility of pathogens and pharmacokinetic properties of
      antibiotics, such as concentration in infected tissue. In patients reluctant to
      medical therapies, surgical intervention such as valve repair or replacement in
      IE and debridement and omental flap in mediastinitis should be considered.

PMID- 11828709
TI  - [Guidelines for antibiotic agents in the field of respiratory tract surgery].
AB  - This paper provides information on the use of antibiotic agents during the
      postoperative period from three aspects. 1) It is important to evaluate the risk
      factors of postoperative infection based on the patient's preoperative condition.
      Diseases treated with respiratory tract surgery are frequently caused by heavy
      smoking. Therefore it must be remembered that the patients may have low
      respiratory function. 2) In the prevention of postoperative infection, the
      special circumstances after respiratory surgery (e.g., the disintegration of the
      clearance system in the airway caused by the dissection of lymph nodes, the
      suppression of respiration, and cough caused by thoracotomy accompanied by
      resection of the ribs) must be considered. Therefore we usually administer
      antibiotic agents for 3 to 4 days. In general, we select second-generation
      cephalosporins, be cause gram-negative rod infection frequently occurs. 3)
      Postoperative infection is diagnosed based on fluctuations in fever, laboratory
      data (number of white blood cells and C-reactive protein), chest X-ray findings,
      and properties of drainage fluid. When bacteria are not identified, we must
      consider MRSA as a gram-positive bacterium and Pseudomonas aeruginosa as a gram
      negative bacterium. After the identification of bacteria causing the infection,
      the antibiotic agents may be changed based on the results of sensitivity tests.
      The appropriate usage of antibiotic agents in the field of respiratory tract
      surgery is discussed based on actual clinical experience in our department.

PMID- 11828710
TI  - [Guidelines for adequate antibiotic prophylaxis after hepatic, biliary, and
      pancreatic surgery].
AB  - The recent spectrum of bacteria isolated from patients with hepatic, biliary, and
      pancreatic infections mostly consists of Gram negative rods translocated from
      their intestinal flora. Cephem or carbapenem antibiotics should be selected based
      on the severity of surgical infection and risk to each patient to prevent
      postoperative infections. Once postoperative infection occurs, surgical
      procedures such as ultrasonography-guided percutaneous biliary drainage should be
      performed to reduce inflammation and to obtain samples for bacterial culture. The
      most commonly identified bacteria after hepatic, biliary, and pancreatic surgery
      are Pseudomonas species, MRSA, and Enterococcus species. Previously administered
      antimicrobial agents should be immediately interrupted and empiric antibiotic
      therapy with carbapenem started. Vancomycin or teicoplanin is selected when MRSA
      or Enterococcus faecium infection is suspected. Infection control systems should
      be in place for prevention of postoperative MRSA infections.

PMID- 11828711
TI  - [Guidelines for perioperative antibiotic use in digestive tract surgery].
AB  - Guidelines for the use of antibiotics in postoperative infections after digestive
      tract surgery have been under discussion in Japan since the mid-1980s, when the
      number of infections with methicillin-resistant Staphylococcus aureus began to
      increase. It is important to make a distinction between prophylactic and
      therapeutic antibacterial administration in the perioperative period.
      Prophylactic antibacterial administration to prevent postoperative infection is
      necessary to prevent surgical site infection and remote infection from invading
      the surgical site. Because the type of bacterial contamination of the surgical
      site differs with the organ undergoing surgery, the type of antibiotic selected
      also differs. Antibiotic administration to prevent postoperative infection after
      surgery requiring a short time to perform may be started preoperatively. In
      patients undergoing prolonged surgery, antibiotics are administered every 3
      hours. If an antibacterial agent is administered for 3-4 days, there is a risk of
      the development of resistance and therefore administration should not exceed 3-4
      days, including the day of surgery. However, during surgery in which bacterial
      contamination is already evident, the therapeutic use of antibiotics should be
      initiated at diagnosis. For example, toxinemia is common in many cases of colon
      rupture and the administration of powerful antibiotics is necessary to save
      patients' lives.

PMID- 11828712
TI  - [Antibiotic management guidelines in trauma and critical care].
AB  - Many patients with severe illness or conditions like multiple trauma and severe
      burns are vulnerable to infection due to their depressed immune function. In
      addition, most patients in the intensive care unit are at increased risk of
      developing ventilator-associated pneumonia and catheter-related sepsis. A basic
      concept of antibiotic use in these guidelines is to diagnose infection and
      identify the pathogenic microorganism as soon as possible. We should not start
      inadequate empirical antimicrobial therapy in cases of undetermined infection
      focus or pathogen because it may increase the risk of development of antibiotic
      resistant bacteria and opportunistic infections. Antibiotic use should be planned
      deliberately from the time of admission in patients hospitalized long time.
      Prophylactic antibiotic use should be restricted to a specific diagnosis or an
      exceptional condition. The antibiotic choice should be determined based on data
      on antibiotic-resistant bacteria in the ward of a trauma center.

PMID- 11828713
TI  - [Alcohol and oropharyngolaryngeal and digestive tract cancer].
AB  - Epidemiology has demonstrated that alcoholic beverages are causally related to
      oropharyngolaryngeal, esophageal, liver, colorectal, and female breast cancer.
      Among Japanese male alcoholics screened by endoscopy combined with esophageal
      iodine staining and immunofecal occult blood tests, 4.2% had esophageal squamous
      cell carcinoma (SCC); 1.2%, oropharyngolaryngeal SCC; 1.4%, stomach
      adenocarcinoma; 1.9%, colorectal adenocarcinoma. The inactive form of aldehyde
      dehydrogenase-2 (ALDH2), encoded by the gene ALDH2*1/2*2, which is prevalent in
      Asians, exposes them to higher levels of acetaldehyde after drinking and was a
      strong risk factor for these cancers among Japanese heavy drinkers. Inactive
      ALDH2 was also associated with synchronous and metachronous multiple esophageal
      cancers. These results suggest a general role of acetaldehyde, an established
      animal carcinogen, in carcinogenesis of the human alimentary tract. The
      oropharyngolarynx and esophagus lack ALDH2 activity, suggesting that after
      exposure to acetaldehyde derived from systemic, mucosal, salivary, or bacterial
      production or alcoholic beverages, these organs' inefficient degradation of
      acetaldehyde enhances the chances for local acetaldehyde-associated
      carcinogenesis. The normal alcohol dehydrogenase-2 (ADH2), encoded by ADH2*1/2*1,
      is another risk factor for oropharyngolaryngeal and esophageal cancer in Japanese
      alcoholics. For patients with both normal ADH2 and inactive ALDH2, the risks for
      oropharyngolaryngeal and esophageal cancer are enhanced in a multiplicative
      fashion. The responses to a simple questionnaire about both current and past
      facial flushing after drinking a glass of beer can indicate an individual's ALDH2
      phenotype fairly well. Use of this questionnaire to obtain information on ALDH2
      associated cancer susceptibility could contribute to the prevention of alcohol
      related cancer in Asians.

PMID- 11828714
TI  - [Cooperative medical care by physicians of general hospitals and psychiatrists of
      an alcoholism treatment unit in Mie Prefecture].
AB  - Clinical practice of psychiatric liaison with physicians is the first step for an
      early treatment of alcohol dependence. Screening patients with alcohol dependence
      in general hospitals, carrying out intervention, and referring them to
      psychiatric specialists are running smoothly by the cooperation of member of the
      Mie Association for the Study of Alcohol-related Diseases. This association is
      being conducted by managers constituted of doctors, nurses, and medical social
      workers and the meeting is held every 6 months at district general hospitals to
      achieve three objectives; 1) evoking a sense of responsibility for alcoholic
      patients in the mind of general hospital staffs, 2) developing a network for
      psychiatric liaison with physicians to care patients of their alcohol dependence,
      and 3) keeping up activities of the association. We have already held the regular
      meeting 12 times, and prepared pamphlets for screening alcohol misuse and for
      early intervention. A course for learning skills of early intervention in this
      summer won the favor of participants. Through case conference of alcoholism and
      full accounts of the experiences given by recovered patients or their families,
      meeting attendants know patients' distress, families' sorrow, and their delight
      brought by the recovery, and are motivated to assist patients with alcohol
      dependence. Thus, "Spirit to Spirit" is a keyword to develop a network of the
      cooperative medical care for supporting patients with alcohol dependence.
      Referral of alcoholic patients to psychiatrists and/or psychiatric liaison
      therapy is promoted by a reliable, faithful, and face to face relationship
      between physicians and psychiatrists. Physicians' learning the skill for early
      intervention in alcohol dependence is followed by an increase in referral of
      patients to psychiatrists, and which suggests the importance of providing
      teaching and training of medical care for alcohol dependence to medical staffs
      including doctors of emergency care units, orthopedics, obstetrics, and
      dentistry. Therefore, systematic tools for screening alcohol dependence in
      general practice, and for referring patients to psychiatrics after brief
      intervention are needed to be prepared under the leadership of a learned society.
      Popularizing the skill of brief intervention in general medical practice is also
      indispensable for advising alcoholic patients about changing their drinking
      pattern or abstinence.

PMID- 11828715
TI  - [Estimated relative and absolute risk for cardiovascular disease according to
      alcohol consumption increase in Japanese general population].
AB  - To calculate the estimated relative and absolute risks for cardiovascular
      diseases according to alcohol consumption increase, we performed a cross
      sectional study of men aged 40-79 years using the data from the National Survey
      of Circulatory Disorders 1990 in Japan. First, we investigated the association
      between alcohol intake and two types of biochemical variables: serum lipids and
      blood pressure, by using analysis of variance. Then, concerning the subjects aged
      40-59 years, linear regression analyses between alcohol intake and these
      biochemical markers were done to calculate regression coefficients adjusted for
      confounding factors. Finally, we substituted these regression coefficients for
      previously reported regression coefficients in Cox proportional hazard models to
      calculate relative and absolute risks for coronary heart disease and stroke.
      Alcohol intake positively correlated to systolic and diastolic blood pressure
      (SBP and DBP) and high-density lipoprotein cholesterol (HDLC). However, there was
      no relation between alcohol intake and serum total cholesterol. Linear regression
      coefficients of SBP, DBP and HDLC were 2.25, 1.43, 2.70, respectively. We used
      two proportional hazard regression formulas of Japanese population: one for
      coronary disease (Circulation 89, 2533-39) and the other for stroke (NIPPON
      DATA80, a 14-year cohort study of randomly selected Japanese). The estimated
      relative risks of coronary heart disease and stroke were 0.89 and 1.06 for 1 "go"
      (23 g of ethanol) increment of alcohol intake. The results indicate that the
      mortality rates shift from 0.44 to 0.39 per 1,000 person-years for coronary heart
      disease and from 0.76 to 0.81 per 1,000 person-years for stroke in the
      representative Japanese population aged 40-59 years. The absolute risk of
      cardiovascular disease may be unchanged if we assume 23 g increment of ethanol
      intake in Japan because the risk reduction in coronary heart disease was nearly
      equal to the risk increment in stroke.

PMID- 11828717
TI  - [Serum levels of mm23-H1 protein and their clinical implications in malignant
      lymphoma].

PMID- 11828716
TI  - Protective effects of cannabinoid receptor ligands analogous to anandamide
      against cocaine toxicity.
AB  - The effects of the endogenous cannabinoid (CB) anandamide (AEA) and its analogs
      on cocaine (COCA)-induced toxic symptoms such as lethality, convulsive seizures
      and hyperactivity were examined in mice. In addition to AEA, the effects of the
      AEA analogs arachidonyl-2-chloroethylamide (ACEA), arachidonylcyclopropylamide
      (ACPA) and R-(+)-methanandamide (METH) were compared to the selective and strong
      CB1 agonist CP 55940 (CP). Intraperitoneal (i.p.) coadministrations of these
      drugs with COCA (75 mg/kg) demonstrated that AEA (10 and 15 mg/kg), ACEA (5
      mg/kg), ACPA (5 mg/kg), METH (5, 10 and 15 mg/kg) and CP (2.5 and 5 mg/kg) all
      antagonized the COCA-induced lethality, and that ACEA (5 and 10 mg/kg), ACPA (5
      and 10 mg/kg), METH (5, 10 and 15 mg/kg) and CP (1, 2.5 and 5 mg/kg) antagonized
      the COCA-induced convulsive seizures. When alterations in the COCA-induced toxic
      behaviors were also evaluated by an activity counting instrument, antidotal
      effects against the COCA-induced hyperactivity were also observed using the above
      doses. The effects against hyperactivity were stronger in the groups of mice
      cotreated with CP or ACEA than in the groups of mice cotreated with AEA or METH.
      However, the antidotal effects against the lethality and convulsive seizures were
      stronger in the METH-treated group than in the AEA-, ACEA- or ACPA-treated
      groups, although the selectivity of METH for brain CB1 receptors was lower than
      for ACEA or ACPA. The correlation with other brain receptors and/or peripheral CB
      receptors seemed to contribute to the strong antidotal effects of METH, which
      were not exceeded even by CP.

PMID- 11828718
TI  - [Clinical significance of WHO classification and MDS 2000 classification in
      myelodysplastic syndromes].
AB  - Excluding chronic myelomonocytic leukemia, a total of 92 consecutive patients
      with myelodysplastic syndrome showing less than 20% blasts in the bone marrow
      were analyzed. We evaluated the clinical significance of the WHO and MDS 2000
      classifications by reviewing each MDS patient according to the classification.
      The WHO criteria classified the MDS patients into 36 with RA, 22 with RCMD and 33
      with RAEB, whereas according to the MDS 2000 criteria there were 19 RAEB-I
      patients and 15 RAEB-II patients. Based on the WHO classification, the RCMD
      patients had higher platelet counts and percentages of blasts among BM cells than
      the RA patients (P = 0.0018, P = 0.0001). Twenty percent of the RA patients,
      44.8% of the RCMD patients, and 70.8% of the RAEB patients had cytogenetic
      abnormalities. Among them, the poor karyotype was present in 6.7% of the RA
      patients, 21.0% of the RCMD patients and 41.6% of the RAEB patients. The rate of
      acute leukemia death was 14.3% in the RA patients, 67.7% in the RAEB patients and
      50.0% in the RCMD patients. Analysis of survival times revealed significant
      differences between RA and RCMD patients (P = 0.0482). The clinical features of
      RCMD patients were intermediate between those of RAEB and RA patients. There was
      no difference between the clinical features of the RAEB-I and RAEB-II patients in
      the MDS 2000 classification.

PMID- 11828719
TI  - [Two cases of bronchus-associated lymphoid tissue lymphoma].
AB  - We report 2 cases of bronchus-associated lymphoid tissue lymphoma (BALT
      lymphoma), which is a rare disease. Patient 1 was a 76-year-old woman with a
      chief complaint of cough. Since plain chest radiography revealed an abnormal
      shadow in the hilum of the lung, she visited our hospital. Patient 2 was a 56
      year-old man, who had been diagnosed as having pseudolymphoma at a medical check
      up in a local hospital. During follow-up, however, he was referred to our
      hospital because of enlarged tumors and chest pain. In both patients,
      bronchofiberscopy demonstrated submucosal tumors and biopsy samples showed
      formation of lymphoepithelial lesions by centrocyte-like cells with a B-cell
      staining pattern. The patients were therefore diagnosed as having BALT lymphoma.
      Both received CEOP-E treatment, which improved the clinical symptoms but did not
      result in complete remission. The patients have been followed up after
      discontinuation of the medication. The progress of the disease has been slow, and
      both patients are alive as of September 2001.

PMID- 11828720
TI  - [Multiple myeloma with Sweet disease developing from monoclonal gammopathy of
      undetermined significance and Sjogren syndrome].
AB  - A 57-year-old woman was diagnosed as having monoclonal IgG kappa gammopathy of
      undetermined significance with Sjogren syndrome. Five years later, she was
      admitted with an increased level of serum IgG and diagnosed as having multiple
      myeloma. After admission, fever and painful erythema developed. Combined
      chemotherapy with adrenal cortical steroid diminished the skin lesions. Erythema
      recurred during treatment with granulocyte colony-stimulating factor for
      neutropenia due to chemotherapy. A biopsy specimen from the skin revealed dense
      neutrophilic infiltration in the dermis, and a diagnosis of Sweet disease was
      made.

PMID- 11828721
TI  - [Preferential infiltration of liver sinusoids in acute lymphoblastic leukemia].
AB  - We report a case of acute lymphoblastic leukemia (ALL) presenting as severe
      jaundice. The patient, a 59-year-old man, was found to have abnormal liver
      function, including an elevated total bilirubin level (13.5 mg/dl) with
      hepatosplenomegaly, but no detectable lymphadenopathy. A liver biopsy and bone
      marrow examination revealed a lymphoid neoplasm. Pathologic features included
      invasion of an abnormal clone into the sinusoidal region of the liver, diffuse
      bone marrow involvement (41.6% of all nucleated cells) and splenomegaly. Small
      numbers of malignant cells were also detected in the peripheral blood. B-cell
      markers, such as terminal deoxynucleotidyl transferase (TdT), CD10, CD19, CD20
      and HLA-DR were positive, and CD2, CD3, CD4, CD5, CD7, CD8, kappa, lambda,
      cytoplasmic mu and myeloperoxidase were negative. Cytogenetic analysis detected
      hyperdiploidy. In this case, a dose-attenuated CHOP regimen attained complete
      remission. To date, preferential infiltration to liver sinusoids has been noted
      in hepatosplenic gamma/delta T-cell lymphoma, other NK/T-cell malignancies, and
      some cases of hairy cell leukemia. Severe jaundice due to preferential
      infiltration of leukemic cells into liver sinusoids is rather uncommon as a
      presenting feature of ALL.

PMID- 11828722
TI  - [Primary splenic CD8-positive diffuse large B-cell lymphoma].
AB  - A 71-year-old woman was admitted for further examination of an increased serum
      LDH level. Abdominal ultrasonography and CT scan showed a large tumor in her
      spleen. Because malignant lymphoma was suspected, the spleen was removed for
      diagnosis and treatment planning. The histopathological and immunohistochemical
      features of the tumor indicated diffuse large B-cell lymphoma (DLBL). The flow
      cytometric immunophenotype of the lymphoma cells was CD2-, CD3-, CD4-, CD5-,
      CD8+, CD10+, CD19+, CD20+, CD23-, kappa+, lambda-, CD25+, and CD56-. From these
      findings, the patient was diagnosed as having CD8+ DLBL. To our knowledge, this
      is the first reported case of primary splenic CD8-positive DLBL.

PMID- 11828723
TI  - [Successful treatment of refractory idiopathic thrombocytopenic purpura by
      eradication of Helicobacter pylori].
AB  - A 53-year-old woman was diagnosed as having idiopathic thrombocytopenic purpura
      (ITP) in 1990, and treated with prednisolone and splenectomy, which did not
      result in remission. In November 2000, gastrointestinal endoscopy showed
      superficial gastritis, and Helicobacter pylori infection was revealed by the
      rapid urease test and histologic examination. After eradication of Helicobacter
      pylori by amoxicillin, clarithromycin and lansoprazole, the patient's platelet
      count was increased from 24 x 10(9)/l to 134 x 10(9)/l and platelet-associated
      IgG (PAIgG) was decreased from 695 ng/10(7) cells to 33 ng/10(7) cells. This case
      suggests that eradication of Helicobacter pylori may be useful for treating some
      patients with refractory ITP.

PMID- 11828724
TI  - [The effect of O2 therapy on mixed venous concentration of endothelin-1 in
      chronic obstructive pulmonary disease].
AB  - Pulmonary hypertension (PH) is an important factor in the prognosis of cases of
      chronic obstructive pulmonary disease (COPD), and endothelin-1 (ET-1) is a major
      factor in the development of PH in COPD. Oxygen (O2) therapy improves the
      prognosis of COPD by suppressing the development of PH. We therefore assessed the
      correlation of PH and ET-1, and the effect of O2 therapy on the plasma ET-1
      concentration. In COPD patients, the plasma ET-1 level in mixed venous blood, but
      not in arterial blood, was negatively correlated with mixed venous O2 tension and
      positively correlated with pulmonary vascular resistance. No such correlation,
      however, was observed in the case of plasma HANP or plasma BNP. O2 administration
      significantly suppressed the plasma ET-1 level. This level in mixed venous blood
      was thought to serve as a marker of PH in COPD. and O2 administration decreased
      the plasma ET-1 level in mixed venous blood. It consequently attenuated PH.

PMID- 11828725
TI  - [Role of neutrophils in acute lung injury induced by Candida sepsis].
AB  - To evaluate the role of inflammatory cells in acute lung injury induced by
      Candida sepsis, we investigated the time course of cell counts in bronchoalveolar
      lavage (BAL) fluid, the lung wet-to-dry weight (W/D) ratio and the CFU of Candida
      after a Candida infection. Male BALB/c mice were injected intravenously with 107
      CFU of Candida albicans. They were sacrificed by exsanguination 0, 6, 12, 18, and
      24 h after infection. The lung W/D ratio was determined in order to assess the
      severity of pulmonary edema. BAL was performed 3 times with 0.5 ml of sterile
      saline. The lung W/D ratio increased significantly 24 h after the injection of
      Candida, and the neutrophil counts in the BAL fluid increased significantly 12,
      18, and 24 h after Candida injection. To assess the effect of neutrophils on
      Candida-induced acute lung injury, we investigated that of neutrocytosis and
      neutropenia on cell counts in BAL fluid, of the W/D ratio, and of the CFU of
      Candida in the lung 24 h after infection. We created neutrocytotic mice using G
      CSF, and neutropenic mice with cyclophosphamide. Peripheral neutrophil counts
      decreased significantly in cyclophosphamide-treated mice, and increased
      significantly in G-CSF-treated mice. The lung W/D ratio increased significantly
      in cyclophosphamide-treated mice. Neutrophil counts in BAL fluid increased
      significantly in G-CSF-treated mice, and decreased significantly in
      cyclophosphamide-treated mice. The CFU of Candida in the lung decreased
      significantly in G-CSF-treated mice, and increased significantly in
      cyclophosphamide-treated mice. We concluded that neutrophils play a protective
      role in Candida albicans-induced acute lung injury.

PMID- 11828726
TI  - [The efficacy of a comprehensive smoking cessation class, combined with nicotine
      patch and gum replacement therapy].
AB  - A six-month comprehensive smoking cessation class was conducted in our hospital,
      and the results were evaluated after one year. To increase the rate of smoking
      cessation, a smoking cessation support team composed of a medical doctor, a
      pharmacist, nurses, a registered dietitian, and a physical therapist was formed.
      The team provided specialized lectures and comprehensive group counseling
      programs every two weeks for the first two months and every month for the next
      four months. Each participant's expired carbon monoxide concentration and body
      weight were measured at every attendance. The participant continued with
      beneficial behavioral treatment for smoking cessation for six months, with
      nicotine replacement therapy (NRT) for the first eight weeks. The protocol of our
      NRT consisted of both the routine use of nicotine patches (Nicotinell TTS) and
      the rescue use of nicotine gum (Nicorette). We first ascertained each
      participant's degree of nicotine dependence, using the Fagerstrom Tolerance
      Questionnaire score, and daily nicotine intake was estimated by a detailed
      questionnaire. We then divided the participants into two NRT groups according to
      their nicotine dependence. The higher nicotine dependence group consisted of
      those whose Fagerstrom Tolerance Questionnaire score was more than 5 points or
      whose estimated nicotine intake was more than 10 mg/day. This group they used
      Nicotinell TTS 30 (TTS 30) for the first four weeks, TTS 20 for the next two
      weeks, and TTS 10 for the last two. In the lower dependence group. TTS 20 and TTS
      10 were each given for four weeks. Nicotine gum use was restricted to 4 pieces a
      day for the first week and reduced by one per day each subsequent week. As a
      result, there was an 81.3% smoking cessation rate after eight weeks, 70.3% after
      six months, and 58.2% after one year. In conclusion, two courses of routine
      nicotine patch use, with the addition of restricted rescue use of nicotine gum,
      can produce better longterm abstinence results than previously reported NRTs,
      suggesting that this may be one of the best ways to cease smoking. We also
      emphasize that intensive group counseling programs and lectures supported by
      doctors and medical teams, as well as a continuing behavioral treatment
      component, may be indispensable for enhancing longterm sustained abstinence
      rates.

PMID- 11828727
TI  - [A case of bird fanciers' disease caused by parrot droppings].
AB  - A 50-year-old woman who had been treated for Parkinson's disease was admitted to
      our hospital because of exertional dyspnea and weight loss. Her chest computed
      tomography showed diffuse ground glass opacities in both lung fields.
      Bronchofiberscopy was performed, and the bronchoalveolar lavage fluid showed an
      elevated lymphocyte count. The serum Ouchterlony test yielded positive results
      for parrot droppings as well as for pigeon serum and droppings. She had had a
      parrot for several years, but no pigeon, and so we diagnosed bird fanciers'
      disease associated with parrot droppings. This responded well to steroid therapy.
      This case of bird fanciers' disease was caused by the droppings of only one
      parrot.

PMID- 11828728
TI  - [A case of primary leiomyosarcoma of the pulmonary artery].
AB  - A 74-year-old woman was admitted to our hospital because of right chest pain. The
      chest radiograph showed right hilar pulmonary artery dilatation. A mass
      exhibiting low intensity in T1-weighted images and high intensity in T2-weighted
      images was disclosed in the right pulmonary artery. Because of its clinical
      course and the MRI findings, the mass was thought to be tumorous tissue, and so
      pneumonectomy was performed. Leiomyosarcoma was diagnosed from the histological
      findings. Primary artery sarcoma is rare and the prognosis is considered to be
      extremely poor. The patient was successfully treated and had a good clinical
      outcome.

PMID- 11828729
TI  - [A case of intrathoracic extension of retroperitoneal fibrosis].
AB  - A 70-year-old man was diagnosed as having retroperitoneal fibrosis 12 years ago.
      The patient was admitted to our hospital with complaints of fever and left chest
      pain. On admission, chest radiography revealed left pleural effusion and left
      pleural thickening. Percutaneous pleural biopsy was performed, and the pleural
      tissue gave a chronic inflammatory reaction characterized by proliferation of
      collagen fibers and chronic inflammatory cellular infiltration. Since the
      retroperitoneal fibrosis had been diagnosed in similar tissue, it was considered
      that this condition had extended to the pleura. On administration of
      prednisolone, the intrathoracic lesions and clinical symptoms were improved, but
      the patient later died of pneumonia. Autopsy showed fibrous pleuritis and chronic
      fibrosing lung disease. This was an extremely rare case. Prednisolone appears to
      be useful in the treatment of intrathoracic extension of retroperitoneal
      fibrosis.

PMID- 11828730
TI  - [Two cases of Chlamydia psittaci infection occurring in employees of the same pet
      shop].
AB  - We report here 2 cases of psittacosis in a pet shop. In the first case, a 44-year
      old male was admitted with fever, and a chest radiograph showed an infiltration
      shadow in the right lower lung. One day later, a colleague of the first patient,
      a 42-year-old man, developed fever and was admitted. In this patient, chest
      radiography revealed an infiltration shadow in the left lower lung. Both patients
      had mild liver dysfunction. The serum titer of a complement fixation (CF) test
      against Chlamydia psittaci was elevated fourfold in the first case and sixteen
      fold in the second on the analysis of paired acute- and convalescent-phase serum
      specimens. Clinical symptoms and abnormal laboratory data were attenuated by the
      administration of minocycline for 2 weeks. Since both patients worked in same pet
      shop and since some parakeets at the shop had died, we speculated that the
      psittacosis had originated from these birds.

PMID- 11828731
TI  - [Pulmonary mucormycosis caused by Cunninghamella bertholletiae in a non
      immunocompromised woman].
AB  - A 74-year-old woman was admitted for further examination because of an abnormal
      nodular shadow and thickening of the bronchovascular bundle in the left upper
      lobe on chest radiography and CT. The findings from a transbronchial biopsy
      specimen were not conclusive. A thoracoscopic lung biopsy specimen revealed a
      fungal infection, and partial resection of S1 + 2 of the left upper lobe was
      carried out. In the dilated bronchus, mucus of high viscosity was seen.
      Lymphocytes and plasma cells had infiltrated into the bronchioles and alveoli.
      Fungus was cultured from the mucus, and the morphological characteristics showed
      Cunninghamella bertholletiae. Pulmonary mucormycosis caused by C. bertholletiae
      in a non-immunocompromised person is very rare. Furthermore, this patient also
      had a wheeze, eosinophilia, elevation of the serum IgE level, and was positive
      for specific IgE to Mucor. We therefore consider that this case was an incomplete
      type of allergic bronchopulmonary fungusis (ABPF).

PMID- 11828732
TI  - [A case of lymphocytic interstitial pneumonia with Sjogren's syndrome and
      systemic lupus erythematosus in which human herpes virus-6 infection was the
      suspected pathogen].
AB  - A 47-year-old-woman was admitted to our hospital complaining of thirst and dry
      cough after catching cold. Sjogren's syndrome (SjS) and systemic lupus
      erythematosus (SLE) were diagnosed. Chest X-P and CT findings suggested strongly
      that she had interstitial pneumonia. Thoracoscopic lung biopsy was therefore
      performed, and the biopsy specimens showed marked infiltration of small
      lymphocytes and of plasma cells into the alveolar walls and interlobular septa.
      Since the infiltrating cells were not atypical and gene analysis did not show
      mono-clonality, we made a diagnosis of lymphocytic interstitial pneumonia (LIP).
      Because the patient's symptoms appeared only after she caught cold, we suspected
      that virus infections were somewhat involved in the etiology of these diseases.
      The level of human herpesvirus-6 (HHV-6) antibody was high, and furthermore, HHV
      6 was detected using the polymerase chain reaction from lung biopsy specimens. We
      suspected in this case that LIP, SjS, and SLE had appeared concomitantly after an
      active HHV-6 infection.

PMID- 11828733
TI  - [A case of primary pleural leiomyosarcoma].
AB  - A 70-year-old man was admitted to our hospital with complaints of chest pain and
      exertional dyspnea. Chest radiography and computed tomography (CT) revealed right
      pleural effusion and pleural thickening on admission. The pleural fluid was
      bloody. Microbiological and cytologic examinations of the fluid were negative.
      The chest CT revealed progress of pleural thickening after hospitalization. A
      thoracoscopic pleural biopsy was performed, and the histological finding of the
      excised specimen was leiomyosarcoma. Because no organ of origin of the
      leiomyosarcoma, other than the pleura, was detected, this case was diagnosed as a
      primary pleural leiomyosarcoma. It is thought that leiomyosarcoma originating
      from the pleura is rare.

PMID- 11828734
TI  - [Chylothorax as the initial manifestation of malignant pleural mesothelioma--a
      case report].
AB  - A case of chylothorax associated with diffuse malignant pleural mesothelioma in a
      53-year-old woman was reported. Chest radiography in a mass examination revealed
      right pleural effusion. A thoracentesis yielded fluid with characteristics
      consistent with chyle. In spite of our suggestion that thoracoscopy for further
      examination was necessary, the patient and her husband had refused the operation
      for months. Chest CT scanning revealed a nodule behind the xiphoid process.
      Lymphoscintigraphy suggested an obstruction of the right parasternal lymphatic
      vessel. Repeated thoracentesis did not yield a diagnosis. As bilateral pleural
      effusion and chylous ascites appeared, dyspnea worsened. About 2 years after the
      mass examination thoracoscopy was performed. On thoracoscopic exploration, a
      nodule was found in the anterior mediastinum and a biopsy was performed.
      Histological analysis revealed that the patient had the epithelial subtype of
      malignant pleural mesothelioma. Thoracoscopic pleural biopsy is a useful means of
      establishing the nature of a chylous effusion. In adult patients with
      chylothorax, thoracoscopic exploration should be performed as soon as possible to
      rule out malignancy.

PMID- 11828735
TI  - [A case of idiopathic interstitial pneumonia that responded well to intermittent
      intravenous administration of high doses of cyclophosphamide and a steroid].
AB  - A 78-year-old man was hospitalized on February 29, 2000 because of dyspnea. A
      chest radiograph showed diffuse bilateral interstitial shadows associated with
      pulmonary volume loss. We could not obtain histological evidence of idiopathic
      interstitial pneumonia (IIP) because of his advanced age and severe respiratory
      dysfunction. IIP was diagnosed on the basis of radiographic findings and clinical
      symptoms. The patient was intubated and mechanical ventilation was performed.
      After one course of pulsed cyclophosphamide (CPM) and methylprednisolone therapy,
      the hypoxemia improved and it became possible to wean the patient from the
      ventilator. After five courses of pulsed CPM therapy, the dose of oral
      corticosteroid was tapered. CPM was administered safely without any severe side
      effects. Pulsed CPM therapy appears to be a viable alternative method of
      treatment for IIP.

PMID- 11828736
TI  - [An autopsy case of idiopathic interstitial pneumonia with diffuse alveolar
      hemorrhage due to acute exacerbation].
AB  - There has hitherto been no report describing idiopathic interstitial pneumonia
      associated with diffuse alveolar hemorrhage, but we herein report one such rare
      case. A 75-year-old man who had received a diagnosis of idiopathic interstitial
      pneumonia had been followed in our hospital since 1995, and had been treated with
      cyclophosphamide since September 1999. He discontinued taking cyclophosphamide
      without informing us, and two months later he was admitted to our hospital with
      deterioration of dyspnea on September 13, 2000. Since chest radiography and CT
      findings demonstrated alveolar infiltrates in the right middle lung field, he was
      treated with antibiotic agents. Although no deterioration of symptoms occurred,
      on September 14 he began to suffer rapidly progressive dyspnea accompanied with
      production of bloody sputum, which eventually developed into full-blown
      hemoptysis in the evening of September 15. He died of respiratory failure early
      the next morning. The autopsy findings demonstrated diffuse alveolar hemorrhage,
      diffuse alveolar damage, interstitial pneumonia, and pulmonary fibrosis.

PMID- 11828739
TI  - [Denture soft lining materials].

PMID- 11828737
TI  - [A case of posterior mediastinal ganglioneuroma with fat tissue].
AB  - We present a rare case of posterior mediastinal ganglioneuroma with fat tissue. A
      50-year-old man visited our Department of Internal Medicine because of
      hypertension and fatty liver. On screening with abdominal CT a soft tissue tumor
      was found in the posterior mediastinum. CT and MRI revealed that the tumor
      appeared to have an abundant fatty component. To obtain a definitive diagnosis,
      the tumor was resected thoracoscopically. The histological diagnosis was
      ganglioneuroma. A ganglioneuroma containing a fat component has rarely been
      reported after cross-sectional imaging. We infer that the tumor may have resulted
      from spontaneous regression, with subsequent infiltration of adipose tissue from
      the posterior mediastinum.

PMID- 11828741
TI  - [Narrowing of the dental pulp cavity in patients undergoing long-term
      administration of steroids].
AB  - The purpose of this study was to examine narrowing of the dental pulp cavity in
      patients undergoing long-term administration of steroids, by means of intraoral
      radiographs. The subjects were 20 patients under long-term steroid treatment (the
      steroid group), and 15 patients who were not receiving steroids (the non-steroid
      group), who visited the Clinic for Persons with Disabilities, University
      Hospital, Faculty of Dentistry, Tokyo Medical and Dental University, between
      April 1994 and March 2000. The dental pulp cavity was divided into the coronal
      area and the root area. Narrowing of each area was classified into three stages
      by means of intraoral radiographs (0, none; 1, moderate; 2, severe). Maxillary
      and mandibular dentition was divided, for purposes of analysis, into anterior,
      premolar, and molar areas, respectively. The narrowing of each part was
      statistically compared between the steroid group and the non-steroid group, using
      the Mann-Whitney U-test. Mean age +/- SD of the steroid group and the non-steroid
      group was 50.5 +/- 17.3 and 51.8 +/- 14.1, respectively. There was no significant
      difference in mean age between the steroid group and the non-steroid group (t
      test). Narrowing of the dental pulp cavity in the steroid group was significantly
      greater than in the non-steroid group, except in the root area of the molar part.
      Since there was no significant difference in mean age between the steroid group
      and the non-steroid group, the greater narrowing in the steroid group was
      concluded to be attributable to the long-term administration of steroids.

PMID- 11828740
TI  - [Effectiveness of a new toothbrush with irrigation and suctioning capabilities
      (ty e-Brush) for removing supragingival plaque].
AB  - Patients with dysphagia typically have poor oral health. Because of improper
      swallowing, they cannot easily and safely clean their mouths. As a solution for
      such a problem, a manual toothbrush with both irrigation and suctioning functions
      has been developed, called the "e-Brush". The purpose of this study was to
      evaluate the cleaning effectiveness of the new e-Brush (9 mm and 11 mm in bristle
      length) for removing supragingival plaque, compared with a conventional
      toothbrush, GUM # 211 by Butler. In this study, 12 subjects (12 female of average
      age 20.6) were selected, and plaque control record (PCR) and scrubbing method
      were used. The following results were obtained: 1. Significant differences (p <
      0.05) were recognized between e-Brush/9 mm (55.54 +/- 18.27%) and the others (e
      Brush/11 mm: 30.88 +/- 8.14%, GUM # 211: 35.42 +/- 9.32%). 2. Bristles 9 mm in
      length were more effective than 11 mm bristles (p < 0.05). 3.
      Irrigation/suctioning function is more effective than the conventional tooth
      brushing method. 4. The irrigation function of e-Brush was meritorious in making
      almost all users comfortable. These results suggest that this new oral hygiene
      device, "e-Brush/9 mm", is effective for improving oral care management for
      patients with dysphagia.

PMID- 11828742
TI  - [Dental treatment in the north area of Ishigaki Island in Okinawa].
AB  - Dental treatment and oral health care were performed on inhabitants in the north
      area of Ishigaki Island in Okinawa. There are no dentists in the area at present.
      One hundred sixty-six patients received treatment taking 528 man-days, during the
      period from November 9 to December 8, 2000. The area has 2 primary schools and 1
      junior high school. The average DMFT of the children in the primary schools was
      1.31, and in the junior high school it was 4.98. Compared with Japanese national
      survey data, the children in the area had a higher DMFT. Among the treatment
      procedures, the rate of conservative treatment was 62%, most of which was
      composite resin filling. Preventive measures for dental disease were offered to
      the inhabitants by means of topical fluoride application or oral health
      education. The period of this promotion was too short to perform complete dental
      treatment and to prevent caries and periodontal disease. It seems that primary
      prevention and higher dental hygiene education are needed for inhabitants in no
      dentist areas, because the inhabitants do not have access to dental service
      easily.

PMID- 11828743
TI  - [Statistical analysis of a dental care program for homebound elderly patients in
      Shinjuku-ku].
AB  - A dental care service program for homebound elderly patients has been operating
      since 1988 in Shinjuku-ku, Tokyo. The purpose of this study was to clarify the
      characteristics of patients who received this dental care service. Based on a
      survey questionnaire and treatment card from April 1995 to March 1999, we
      analyzed the characteristics of patients. The following conclusions were
      obtained. 1. We studied 301 patients (males, 124; females, 177). The average age
      of the patients was 81.2 +/- 9.0 years. Eighty-four percent of the patients had a
      medical history. 2. Oral hygiene was practiced by 68% of the subjects: 78% by
      themselves, and 22% by caregivers. Half of the patients (53%) brushed their teeth
      every day, and one-third (32%) did not. 3. The mean number of DMF teeth was 25.4
      (DT, 1.6; MT, 20.5; FT, 3.3). 4. About eighty percent (79%) of the patients had
      removable dentures, and one-third of them were upper and lower complete dentures.
      5. The chief complaint of homebound elderly was the denture problem (73%).
      Therefore, the care provided at the bedside was mainly denture-related
      treatments. 6. Average times for visiting were 5.1. 7. Sixty-eight percent of the
      patients requested home dentist's visitation for dental care service, and 80% of
      the requested dentists performed such treatment. 8. Seventy-eight percent of the
      elderly patients were satisfied with the service program. This dental care
      program for homebound elderly patients seemed to work well. However, to meet
      needs for the expanding number of aged persons and to make it coincide with the
      new health and welfare scheme, reform of the program might be necessary.

PMID- 11828744
TI  - [Development of new reactions and their pharmaceutical application based on the
      molecular structure characteristics].
AB  - The author and his group have been developing new reactions based on molecular
      structure characteristics; sigma-symmetric bifunctional molecules, dipole-dipole
      repulsion, active amide structures, latent active species, orbital-orbital
      interactions, nonbonded interactions, strained structures, allenic structures,
      etc. Various new reactions such as asymmetric aminolyses and Dieckmann-type
      cyclizations of prochiral sigma-symmetric dicarboxylic diamides, asymmetric aldol
      type reactions onto gamma-hydroxybutenolides and asymmetric imine alkylations
      onto omega-acetoxy lactams using chiral Sn(II) enolates, asymmetric Pummerer-type
      reactions, cascade reactions and endo-mode cyclizations exploiting alpha,beta
      unsaturated allenic esters and ketones, base- and palladium-promoted ring
      expansion reactions, and syntheses of alpha-substituted serines and 1-azabicyclo
      [1.1.0] butane have been achieved. These new reactions were applied to the
      synthetic development of new seed and lead compounds (SH-enzyme inhibitors, tumor
      inhibitors, and antibiotics) with the aim of synthesizing new drugs. Asymmetric
      syntheses of (+)-Prelog-Djerassi lactonic acid methyl ester, (+)-carbacyclin, ISP
      I (myriocin), (+)-conagenin, Geissman-Waiss lactone, biapenem (a new carbapenem
      antibiotic), thienamycin-like gamma-lactam, and bicyclic alkaloids were also
      achieved by utilizing these reactions. Evaluation and molecular design of the
      seed and model compounds for angiotensin II receptor antagonists, tumor
      inhibitors, and antibiotics have been investigated on the basis of QRSA and/or
      nonbonded S...X (X=O, N, S, halogens) interaction concepts.

PMID- 11828745
TI  - [Effect of admixture of commercially available corticosteroid ointments and/or
      creams on vasoconstrictor activity].
AB  - A commonly used admixture of commercially available ointments and/or creams was
      selected from the prescribed sheets in our hospital, and questionnaire to
      dermatologists. To assess the relationship between permeability of corticosteroid
      through murine skin and clinical effects in human, we attempted to investigate
      the vasoconstrictor activity of these admixtures of topical corticosteroid by
      double-blind controlled study. Test samples were occluded at random on the back
      of 20 healthy volunteers for 4 hours. The vasoconstrictor activity of
      corticosteroid creams (Lidomex) alone was significantly large as compared with
      that of ointments alone. The vasoconstrictor activity of corticosteroid in the
      admixture of Lidomex ointment and urea ointments or heparinoid ointment was 1.5-2
      fold significantly larger than that from ointments alone. The extent of the
      stability of the emulsion after mixing was related to the vasoconstrictor
      activity. These experiments demonstrated a close relationship between the
      vasoconstrictor activity of human skin and permeability of hairless mice skin.
      These results suggested that the vasoconstrictor activity of topical
      corticosteroids mixed with commercially available ointments and/or creams depends
      upon their physicochemical characteristics.

PMID- 11828746
TI  - Developing and integrating an adverse drug reaction reporting system with the
      hospital information system.
AB  - We have developed an adverse drug reaction (ADR) reporting system integrating it
      with Hospital Information System (HIS) of the University of Tokyo Hospital. Since
      this system is designed with JAVA, it is portable without re-compiling to any
      operating systems on which JAVA virtual machines work. In this system, we
      implemented an automatic data filling function using XML-based (extended Markup
      Language) files generated by HIS. This new specification would decrease the time
      needed for physicians and pharmacists to fill the spontaneous ADR reports. By
      clicking a button, the report is sent to the text database through Simple Mail
      Transfer Protocol (SMTP) electronic mails. The destination of the report mail can
      be changed arbitrarily by administrators, which adds this system more flexibility
      for practical operation. Although we tried our best to use the SGML-based
      (Standard Generalized Markup Language) ICH M2 guideline to follow the global
      standard of the case report, we eventually adopted XML as the output report
      format. This is because we found some problems in handling two bytes characters
      with ICH guideline and XML has a lot of useful features. According to our pilot
      survey conducted at the University of Tokyo Hospital, many physicians answered
      that our idea, integrating ADR reporting system to HIS, would increase the ADR
      reporting numbers.

PMID- 11828747
TI  - Studies on toad venom (3): effect of metals on the quality of toad venom
      torrefied on a metal plate.
AB  - To study the quality of toad venom dried on different metal plates by heating at
      105 degrees C, each 20 g sample of fresh toad venom collected in Hei-Long-Jiang
      Province, China, was dried on (1) brass, (2) copper, (3) glass, (4) acrylic
      resins, (5) aluminum and (6) stainless-steel, respectively. Twelve
      bufadienolides, including bufalin and bufotalin, in each sample were then
      quantitatively analyzed by HPLC. The total levels of bufadienolides in 1000.0 mg
      of the dried samples were (1) > (2) > (3) > (4) > (5) > (6), varying from 303.44
      mg to 420.72 mg. Besides, the color of dried venom became darker in the order of
      (2), (4), (6), (3), (1) and (5). Though (1) was not in good color, it was
      superior to the others in chemical quality. These results suggest that it is
      possible to dry toad venom in short period by heating it at a high temperature on
      a tray made of brass. This will be a better method for making high quality toad
      venom than the traditional method. Moreover, the removal of impurities in the
      fresh venom by the process of filtration through silk succeeded in raising the
      bufadienolides content significantly.

PMID- 11828748
TI  - [Studies on residue on ignition test in JP].
AB  - The Residue on Ignition Test specified in General Tests, Japanese Pharmacopeia is
      a method to measure the weight of the residual substance not volatilized when the
      sample is ignited under a constant condition. Generally, this test is intended to
      determine the content of inorganic substances contained as impurities in an
      organic substance, and, occasionally, to determine the amount of inorganic
      substances contained as components in an organic substance. Our laboratories have
      adopted this test method for the above two purposes in the case of the quality
      control for drug substances, synthetic intermediates, starting materials in the
      course of drug development. Some validation studies have been conducted for this
      test in order to clarify the quantitation limit in the case of an application for
      the former purpose, and trueness and precision in the case of the latter purpose.
      Consequently, the quantitation limit was determined as around 0.50 mg. The amount
      of sample should be determined based on this quantitation limit (mg) and the
      level of quantitation limit (%) or that of specification limit (%) should be
      considered from the view point of each testing purpose. The test method was also
      confirmed to have a good trueness and precision as the determination method for
      an alkaline salt, such as sodium, potassium or calcium salt, of organic
      compounds, as long as the test is operated with great care not to scatter the
      content out of crucible during ignition to incineration.

PMID- 11828749
TI  - [Molecular design and function of ate complexes].
AB  - Lithium trialkylzincates were known to be convenient and synthetically useful for
      transferring various organic moieties and for metallating aromatic halides or
      vinyl halides. The outer shell of the zinc atom in lithium trialkylzincates is
      filled with 16 electrons, and there is a room for an additional ligand to
      coordinate to form a favorable state with 18 electrons. As a new type of zincate,
      the reactivities of this tetraalkylorganozincates and related modified
      organozincates were then studied. 1H-NMR study of organozincates indicated the
      difference between these highly coordinated zincates and lithium
      trimethylzincate. And the studies on the reactivity disclosed the difference of
      regioselectivity for epoxide opening reaction and the different reactivity toward
      halogen-metal exchange reaction. These results support that these highly
      coordinated zincates should be distinguished from ordinary lithium
      trialkylzincates in the structure and the reactivity. On the other hand, various
      dialkylzinc hydride "ate" complexes were also designed and the reactivities of
      these zincates toward the carbonyl compounds were investigated. The results
      clearly reveal that dimethylzinc hydrides are the most powerful and selective
      zincate for the reduction of the carbonyl group.

PMID- 11828750
TI  - [Molecular biological studies on diversity of secondary metabolism in medicinal
      plants and application to the production in transgenic plants].
AB  - A molecular biological approach was applied to the study of diversity and
      regulation of secondary metabolism in medicinal plants at various levels. For the
      inter-species diversity, RFLP (restriction fragment length polymorphism) and RAPD
      (random amplified polymorphic DNA) analyses of genomic DNA were performed on the
      plants, belonging to the same genus or family and containing related compounds.
      Phylogenetic trees of lupin alkaloid containing plants and other medicinal
      plants, based on RFLP and/or RAPD profiles, showed the relationship between the
      diversities in genomes and secondary metabolisms. The chemotypes regarding
      anthocyanin production in Perilla frutescens var. crispa, were subjected to the
      study on intra-species diversity. The structural genes and the regulatory genes
      involved in anthocyanin biosynthesis were isolated and their expression in red
      and green forms was determined by Northern blot analysis. The expression of all
      structural genes examined was co-ordinately regulated in form-specific manner and
      by light illumination. The anthocyanin production was enhanced in transgenic
      plants over-expressing Myc homologue genes from perilla. These results suggested
      that a protein complex including bHLH factors might regulate the expression of a
      series of structural genes. Additionally, cDNAs coding anthocyanin 5-O
      glucosyltransferase and anthocyanidin synthase were isolated and characterized
      using recombinant proteins for the time. In conclusion, it was indicated that the
      molecular biological techniques are powerful tools for the investigation of
      diversity and regulation of and for the genetic engineering of secondary
      metabolism in medicinal plants.

PMID- 11828752
TI  - [Development of new methods in asymmetric reactions and their applications].
AB  - Several novel methods using chiral reagents and biocatalysts for asymmetric
      reactions are described. Among those reactions, asymmetric reduction via a novel
      tandem Michael addition/Meerwein-Ponndorf-Verley reduction of acyclic alpha,beta
      unsaturated ketones using a chiral mercapto alcohol, asymmetric synthesis of
      allene-1,3-dicarboxylate via crystallization induced asymmetric transformation,
      and improved asymmetric nitroolefination of lactones and lactames at alpha-carbon
      using new chiral reagents were developed. In the reactions using biocatalysts,
      asymmetric dealkoxycarbonylation of bicyclic beta-keto diesters having sigma
      symmetry with lipase or esterase to give optically active beta-keto esters, the
      asymmetric reduction of bicyclic 1,3-diketones having sigma-symmetry with Baker's
      yeast to give optically active keto alcohols, and the asymmetric aldol reaction
      of glycine with threonine aldolase were also developed. The above mentioned
      products were effectively utilized as chiral building blocks for the asymmetric
      synthesis of natural products and drugs.

PMID- 11828751
TI  - [Development of transdermal formulation of tulobuterol for the treatment of
      bronchial asthma].
AB  - beta 2-Adrenergic agonists have been widely used to treat patients with asthma.
      Usually, oral dosage forms of beta 2-agonists have been used, but side effects
      such as palpitation and tremor have been reported because of excessive serum
      levels around Tmax. It is said that circadian variations exist in the
      manifestation of asthma with maximum incidence of asthma attacks in early morning
      at around 4 a.m., the so-called morning dip. Chronotherapy for asthma based on
      circadian rhythm should be more efficient and have a lower frequency of side
      effects. Accordingly we developed a transdermal delivery system of the beta 2
      agonist tulobuterol adapted to the circadian rhythm. The system is designed to
      administer the appropriate dose of the drug at an optimal time using the so
      called Crystal Reservoir System. The superiority of the transdermal formulation
      of tulobuterol over the current therapy using oral formulations of beta 2
      stimulants was indicated by its excellent pharmacokinetic profile, and confirmed
      by the results of clinical trials. This formulation is the first transdermal
      chrono-delivery system reported anywhere in the world, and is expected to provide
      more effective and safe treatment of asthma and related diseases not only in
      adults, but also especially in children.

PMID- 11828753
TI  - [Investigation of actual use of laxatives and application to the active drug
      information offer in drug control guidance].
AB  - On the therapy of constipation, there are few reports that surveyed the actual
      circumstance of patients taking laxatives and the effectiveness of the drug. In
      this study, we investigated the contents in prescription, the actual conditions
      of administration of laxatives, and the subjective symptoms of inpatients in all
      wards of Kanazawa University hospital (2000. 12.1-2000. 12. 10). As a result of
      the investigation, the percentage of patients prescribed some laxatives was found
      to be about 31.5% (274) of all hospitalized patients (871), and among them about
      16% (43) of the patients had some problems in defecation control. One of the
      causes leading to the problems for some patients (11) among them seemed to be due
      to the lesser amount of magnesium oxide taken per day. Then, in the ophthalmology
      ward we further investigated the proper use of laxatives and the defecation
      condition of the patient using a questionnaire paper and a record paper (20
      cases). Patients became constipated by hospitalization, and although being
      administered some laxatives, they were often insufficient to control the
      defecation. Some patients (7) with changeable defecation control could be
      improved by change or addition of prescription. Pharmacist concerned 5 cases of
      patients with change or addition of prescription. This study indicates that
      pharmacists should actively offer information and rational usage of laxatives to
      doctors and patients.

PMID- 11828754
TI  - Introduction of simple swallowing ability test for prevention of aspiration
      pneumonia in the elderly and investigation of factors of swallowing disorders.
AB  - Aspiration pneumonia is a major cause of death in the elderly. In this study, a
      water swallowing test was introduced as a method of evaluating the swallowing
      ability of patients, and a swallowing ability evaluation team investigated an
      appropriate procedure and evaluation method for the situation of our hospital. We
      also investigated the relationship between the swallowing ability of patients
      examined by the water swallowing test and underlying diseases, complications, and
      medicated drugs. In the water swallowing test, the water-drinking method was
      fixed, and evaluation was made based on the time required for drinking, profile,
      and episodes, by which patients suspected of swallowing disorder were detected,
      confirming the usefulness of this method. The frequency of developing swallowing
      disorder was significantly higher in patients with cerebrovascular disorders,
      Parkinson's syndrome (p < 0.01, respectively) and symptomatic epilepsy,
      hypertension (p < 0.05, respectively) as underlying disease/complication.
      Regarding medicated drugs, H2 blockers were related to swallowing disorder (p <
      0.05). It was confirmed that patients who were judged as having swallowing
      disorder (including suspected cases) by the water swallowing test, and patients
      with underlying diseases and complication that may cause the disorder, and
      patients medicated with drugs that may affect the swallowing ability require
      appropriate management by medical care staff.

PMID- 11828755
TI  - [New trend in radiology].

PMID- 11828756
TI  - [Current practice in MR imaging of the liver].
AB  - MR imaging, which is able to evaluate T1- and T2-relaxation time, fat,
      hemorrhage, metal deposition, blood flow, perfusion, diffusion, and so on, has
      offered more information for the diagnosis of diffuse and focal hepatic diseases
      than CT. The spoiled-GRE sequence with high contrast resolution and ease of the
      aimed contrast capture derived from the k-space property, with the use of a
      phased-array multicoil, have remarkably increased the value of gadolinium
      enhanced dynamic MR diagnosis of the liver. In recent years, the clinical use of
      ferumoxide has begun, and issues concerning the superiority or inferiority and
      combination of contrast media are being debated. This paper describes the value,
      role, and clinical practice of unenhanced, gadolinium-enhanced, and ferumoxide
      enhanced MR imaging of the liver based on knowledge obtained in our institution,
      with some reference to the literature.

PMID- 11828757
TI  - [Usefulness of enhanced ultrasonography after administration of intravenous
      contrast agent in the evaluation of therapeutic effect in treatment of
      hepatocellular carcinoma, and efficacy of percutaneous ethanol injection therapy
      (PEIT) for residual tumor].
AB  - PURPOSE: To investigate the usefulness of enhanced ultrasonography after the
      administration of intravenous contrast agent in the evaluation of therapeutic
      effect in the treatment of hepatocellular carcinoma (HCC) comparison with dynamic
      CT, and to examine the efficacy of percutaneous ethanol injection therapy (PEIT)
      for residual tumor. MATERIALS AND METHODS: Thirty patients (22 men, 8 women; age
      range, 42-76 years; mean age 60 years) underwent enhanced ultrasonography with
      the intravenous ultrasonographic agents Levovist, after transcatheter arterial
      embolization (TAE) (n = 15, size range 23-35 mm, mean 25.3 mm) or PEIT (n = 15,
      15-35 mm, mean 24.5 mm), to compare the therapeutic effect with dynamic CT. If
      residual lesions were detected by enhanced ultrasonography, we performed
      additional PEIT. RESULTS: The evaluation of enhanced ultrasonography correlated
      almost completely with that of dynamic CT. Two residual lesions could not be
      detected by dynamic CT due to lipiodol, but enhanced ultrasonography and dynamic
      MRI showed them clearly. In total, eight residual tumors (3-15 mm, mean 8.3 mm)
      were seen. We performed PEIT on seven lesions and obtained good control for six
      months. CONCLUSION: Enhanced ultrasonography with Levovist could be performed to
      evaluate the therapeutic effect of treatment for HCC, and could serve as be a
      good marker for additional US-guided therapy.

PMID- 11828758
TI  - [Radiofrequency ablation of rabbit liver: correlation between CT findings and
      pathological findings].
AB  - The purpose of this study was to present the time-related imaging findings and
      correlative pathological findings of irradiated regions in the rabbit liver. RF
      ablation was carried out on 16 rabbit livers. Irradiated regions were imaged at 3
      days, 4 weeks, and 12 weeks. At 3 days, the regions showed a two-zone structure
      on plain CT and peripheral enhancement on the arterial phase. The regions
      presented a three-zone structure on pathological study. At 4 weeks, peripheral
      enhancement had almost disappeared, and a two-zone structure obscured on plain
      CT. The CT findings reflected pathological changes after RF ablation.

PMID- 11828759
TI  - [Subependymoma of the lateral ventricle: a case report].
AB  - We report a case of subependymoma of the right lateral ventricle in a 59-year-old
      man. CT revealed a mass lesion in the right lateral ventricle. No calcification
      was seen in the tumor, and the right lateral ventricle was dilated dominantly by
      the tumor. The tumor showed intermediate intensity on T1-weighted MR images and
      high intensity on T2-weighted MR images. On contrast study, the tumor showed
      heterogeneous enhancement. We suspected this to be a case of central neurocytoma,
      and surgical resection was performed. The histological diagnosis was
      subependymoma, but we considered it difficult to differentiate from astrocytoma,
      central neurocytoma, and ependymoma.

PMID- 11828760
TI  - [Clinical study of corneal endothelial cells].

PMID- 11828761
TI  - [Preoperative factors influencing visual acuity following vitrectomy for
      exudative age-related macular degeneration].
AB  - PURPOSE: We investigated the relations between ingrowth site and visual results
      in patients undergoing surgical removal of subfoveal choroidal neovascular
      membranes (CNV) caused by age-related macular degeneration (AMD). MATERIALS AND
      METHODS: The subjects were 70 eyes(69 patients), which underwent surgical removal
      of CNV for AMD and were followed up for 6 months or more. The eligibility
      criteria were active subfoveal choroidal neovascular membrane 3 disc diameters
      (DD) or less in size located above the retinal pigment epithelium, and visual
      acuity of 0.3 or worse. We analyzed the relationships between postoperative best
      corrected visual acuity and preoperative factors: ingrowth site of CNV, distance
      between the fovea and the CNV edge, CNV size, and fluorescence pattern in
      indocyanine green angiography (IA). RESULTS: Patients 1) with feeder vessels
      located outside the foveal avascular zone (FAZ) rather than inside the FAZ and/or
      unknown feeder vessels, 2) with a distance between the fovea and the CNV edge 0.2
      DD or less than 0.2 DD versus larger, than 0.2 DD 3) with a 1 DD or smaller CNV
      versus 1.5 DD or larger, and 4) type I, II, or III findings in IA rather than
      type IV had good postoperative best-corrected visual acuity. CONCLUSIONS: To
      achieve better postoperative visual acuity after surgical removal of CNV
      associated with AMD, it is important to select CNV with ingrowth sites outside
      the FAZ, small and large CNV with a relatively short distance between the fovea
      and the CNV edge closest to the fovea, and type I, II, and III findings in IA.

PMID- 11828762
TI  - [Correlation between birefringence and histopathologic figures of keratoconus and
      bullous keratopathy].
AB  - PURPOSE: We studied macroscopic pictures with polarizing filter and microscopic
      pictures of the corneas in keratoconus and bullous keratopathy. METHOD: Among
      penetrating keratoplasty specimens referred to the National Defense Medical
      College, we investigated 16 keratoconus and 189 bullous keratopathy specimens.
      Macrophotographs with polarizing filter and light microscopic photographs
      (hematoxylene-eosin staining) were investigated. The hyperbolic polarizing
      pattern, stromal thickness of corneal specimens and number of fibroblast-like
      cells in the stroma were analyzed. RESULT: Hyperbolic polarizing patterns
      depended on the number of fibroblast-like cells in the stroma and the thickness
      of the stroma, but hyperbolic polarizing patterns had no relation with the
      epithelium or endothelium of the cornea.

PMID- 11828763
TI  - [Corneal endothelial cell changes in triple procedure].
AB  - PURPOSE: A retrospective study was performed to examine time-related changes in
      the corneal endothelium in eyes that underwent a triple procedure consisting of
      penetrating keratoplasty, extracapsular excision, and intraocular lens (IOL)
      insertion. MATERIALS AND METHODS: We studied 39 eyes from 36 patients who
      underwent a triple procedure associated with corneal transplantation at Tokyo
      Medical University between February 1989 and May 1996. The ages of the patients
      at the time of operation ranged from 61 to 91 years (mean, 70.9 +/- 10.8 years).
      The postoperative follow-up period ranged from 13.6 to 107.5 months (mean, 53.4
      +/- 27.1 months). The following were evaluated: 1) cure rate of transparency, 2)
      complications, 3) time-related changes of endothelial cell density during 7 years
      after operation, and 4) comparison of changes in endothelial cell density
      associated with various factors such as primary disease, graft, IOL, and
      rejection. RESULT: The following results were obtained. 1. The cure rate of
      transparency of the graft at the last examination(a mean of 53.4 +/- 27.1 months
      after surgery) was 82.1%. 2. The incidence of rejection at the last examination
      was 35.9%. 3. The mean endothelial cell density in the graft was 2945.8 cells/mm2
      before operation, and decreased to 1806.7 cells/mm2 one year after operation, and
      further to 1161.1 cells/mm2 five years after operation, showing a reduction of
      60.6% compared to the mean before operation. 4. The annual rate of endothelial
      cell reduction in the same patient was approximately 25% the first year after
      operation and gradually lessened from the second year, reaching a stable level of
      6% after the third year. 5. The punching method(done from the epithelial side),
      diameter of optical zone of IOL (6 mm or less), and rejection contributed to the
      reduction of endothelial cell density by one year after the operation.
      CONCLUSION: The triple procedure is considered to be a technique that may be
      chosen actively.

PMID- 11828764
TI  - [Histological study of conjunctiva-associated lymphoid tissue in mice].
AB  - PURPOSE: To investigate conjunctiva-associated lymphoid tissue (CALT) in mouse
      conjunctiva. METHOD: We examined normal mice, ranging in age from 4 to 6 weeks,
      to investigate the presence of follicular tissue histologically. Next, we treated
      mice by topical instillation of ovalbumin and cholera toxin B, and then examined
      conjunctival follicles by immunohistological methods. RESULTS: Follicular tissue
      was present at the nictitating membrane. Both size and amount of follicular
      tissue was increased by the topical ovalbumin treatment. Immunohistological
      examination revealed CD4, CD8, and S-100 protein positive cells in follicular
      tissue. The epithelial layer, corresponding to follicular tissue, had
      intraepithelial pockets and CD4 positive cells in the pockets. CONCLUSION: It was
      concluded that the follicular tissue at the nictitating membrane is CALT in mice.

PMID- 11828765
TI  - [Vertical vergence adaptation in cases of superior oblique palsy].
AB  - PURPOSE: To investigate the characteristics of vertical adaptation (VA) in
      superior oblique muscle palsy (SOP). SUBJECTS AND METHODS: VA was examined in 15
      patients with unilateral congenital SOP, 7 patients with unilateral acquired SOP,
      and 35 normal volunteers. An adaptive change in the fusion-free ocular alignment,
      VA, was measured with a computer-aided mirror haploscope. The fusion-free ocular
      alignment was measured before inserting a 3 prismdiopter vertical prism,
      immediately after inserting the prism, and at 10 minutes and 30 minutes after
      insertion. We investigated VA gain, age, vertical fusional range, response of
      prism adaptation test (PAT), and superior oblique muscle atrophy in magnetic
      resonance imaging (MRI). RESULTS: The VA gain (mean +/- standard deviation, %) at
      30 minutes in congenital, acquired, and normal groups was 86 +/- 53, 34 +/- 23
      and 58 +/- 16, respectively. The mean of the VA gains at 30 minutes in the
      congenital group was greatest, and that in the acquired group was least(p <
      0.01). In the congenital group there was a correlation between VA gain and
      response of PAT (p = 0.02, r = 0.60). The VA gain did not significantly correlate
      with age, vertical fusional range, or muscle atrophy. CONCLUSION: The VA gain
      observed in congenital SOP was greater than that of acquired SOP, and affected
      the response of PAT.

PMID- 11828766
TI  - [A clinical evaluation of uveitis-associated secondary glaucoma].
AB  - PURPOSE: To investigate the clinical features of secondary glaucoma associated
      with uveitis. SUBJECTS AND METHODS: The subjects of the study were 1,604 eyes of
      1,099 patients with uveitis at Miyata Eye Hospital, Miyakonojo, Miyazaki, between
      October 1974 and January 2000. The intraocular pressure (IOP) and clinical data
      were analyzed retrospectively. Secondary glaucoma was defined as being an IOP
      higher than 21 mmHg and needing treatment with medication to control the high
      IOP. RESULTS: Secondary glaucoma was found in 293 eyes (18.3%) of 217 patients
      (19.7%) among the uveitis patients. The clinical entity with the highest
      frequency of secondary glaucoma was Posner-Schlossman syndrome in 100%, followed
      by sarcoidosis in 34.1%, herpetic anterior uveitis in 30.4%, Behcet's disease in
      20.8%, HLA-B 27 related acute anterior uveitis in 20.0%, Vogt-Koyanagi-Harada'
      disease in 16.4%, and HTLV-1 uveitis in 16.2%. Among the 293 eyes with secondary
      glaucoma, the majority (72%) had active anterior uveitis at the time of high IOP.
      Only 7.5% of secondary glaucoma eyes had peripheral anterior synechia wider than
      180 degrees of trabecular meshwork. Steroid glaucoma was found only in 8.9% of
      the secondary glaucoma eyes. Surgical therapy mainly with trabeculectomy with
      anti-metabolites was performed in 38 eyes and the postsurgical IOP was controlled
      to 20 mmHg or lower in 36 eyes. Despite the medical and surgical therapy for
      secondary glaucoma, defect of the visual field was found in 38% of the secondary
      glaucoma eyes. CONCLUSIONS: The frequency of secondary glaucoma in 1,604 eyes
      with uveitis was 18.3%, and the frequency of secondary glaucoma differed
      depending upon the clinical entity of uveitis. The evaluation and the management
      of IOP are very important in treatment patients with uveitis, in addition to the
      management of intraocular inflammation.

PMID- 11828767
TI  - [A case of choroidovitreal neovascularization after unsuccessful laser
      chorioretinal venous anastomosis for central retinal vein occlusion].
AB  - BACKGROUND: A case of nonischemic central retinal vein occlusion, which developed
      severe neovascular complication after unsuccessful laser chorioretinal venous
      anastomosis is reported. CASE: The patient was a 50-year-old man with nonischemic
      central retinal vein occlusion of the right eye. Two weeks after laser
      chorioretinal venous anastomosis attempt, closure of the venous segment distal to
      the anastomotic sites occurred and a choroidovitreal neovascularization
      developed, so that vitreous surgery was needed 2 months after the laser attempt.
      CONCLUSION: Laser chorioretinal venous anastomosis should be used only on
      carefully selected patients, and close follow-up is needed after this treatment.

PMID- 11828768
TI  - [Levels of mature cross-links and advanced glycation end product cross-links in
      human vitreous].
AB  - PURPOSE: To determine the levels of pyridinoline and deoxypyridinoline, two
      mature enzymatic cross-links, and pentosidine, an advanced glycation end product
      (AGE) cross-link, in human vitreous and to investigate the correlations among the
      cross-links and the effects of aging and diabetes mellitus (DM) on the levels of
      the cross-links. METHODS: Forty-five vitreous samples were collected from 32 eyes
      undergoing vitrectomy for diabetic retinopathy (DM group) and 13 eyes (control
      group) from age- and sex-matched patients with idiopathic macular hole or
      epiretinal membrane with no systemic conditions. The levels of the cross-links
      were determined using high-performance liquid chromatography after acid
      hydrolysis and pre-treatment with SP-Sephadex. RESULTS: The levels of
      pentosidine, pyridinoline, and deoxypyridinoline were 27.3 +/- 23.1(mean +/-
      standrard deviation) pmol/ml (n = 45), 79.0 +/- 40.2 (mean +/- standrard
      deviation) ng/ml (n = 43), and 54.0 +/- 9.5 ng/ml (n = 32), respectively. When
      the vitreous samples from DM and the controls were compared, a significant
      difference (p < 0.05) was found in the level of pentosidine but not in the levels
      of pyridinoline or deoxypyridinoline. No significant correlations were found
      between age and the cross-links. Significant correlations (p < 0.01) were found
      among the cross-links. CONCLUSIONS: The results indicate that mature cross-link
      substances exist in human vitreous. The results also suggest that glycation may
      occur in the vitreous after mature cross-links form and result in the formation
      of AGE cross-links. In human vitreous from patients with DM, increased levels of
      AGE cross-links may stabilize the formation of mature cross-links but did not
      increase mature cross-links.

PMID- 11828769
TI  - [Transurethral endoscopic treatment for chronic hematospermia caused by mullerian
      duct cyst and ejaculatory duct obstruction].
AB  - Between June 1997 and September 1999, we performed transurethral unroofing (TUUR)
      in three patients with hematospermia that recurred repeatedly for one year or
      more. Patient 1 (48 years old) and Patient 2 (59 years old) were diagnosed as
      having mullerian duct cysts that communicated with the left ejaculatory duct, and
      Patient 3 (36 years old) as an ejaculatory duct obstruction with the right
      ejaculatory duct dilation. A mixture of water-soluble contrast medium and
      indigocarmine blue dye was injected into the cysts and the ejaculatory duct
      cavity after incision of the vas deferens in Patients 1 and 3, and by cyst
      puncture under transrectal ultrasound (TRUS) guidance in Patient 2. Then the
      urethra was incised between the bladder neck and the verumontanum using a
      Collins' hot knife electrode, and spouting of the dye from the incision was
      judged to indicate successful unroofing. In Patient 2, safe and simple TUUR was
      possible by identifying the cyst location and its distance from the knife
      electrode under TRUS guidance. Hematospermia resolved after surgery in all three
      patients and there has been no recurrence for 1.3-3.5 years (mean: 2.6 years).
      Thus, TUUR was effective for treating chronic hematospermia caused by mullerian
      duct cyst and ejaculatory duct obstruction. For safe and reliable performance of
      this treatment, TRUS guidance and injection of the dye into the cyst and
      ejaculatory duct cavity can be recommended.

PMID- 11828770
TI  - [The prediction of bladder outlet obstruction with prostate volume, maximum flow
      rate, residual urine and the international prostate symptom score in patients
      with lower urinary tract symptoms].
AB  - We determined whether prostate volume (PV), maximum flow rate (Qmax), residual
      urine (RU) and the International Prostate Symptom Score (I-PSS) predicted bladder
      outlet obstruction in patients having lower urinary tract symptoms (LUTSs). The
      study consisted of 114 patients aged 50 years or older with LUTSs who had scores
      of 8 or more on the I-PSS and 2 or more for the quality of life index. All
      patients received transrectal ultrasonography for estimation of PV and pressure
      flow study (PFS). When PFS showed an obstruction grade of 2 or more in Schafer's
      p/Q diagram, the result was defined as bladder outlet obstruction. When we
      examined which criteria indicated that 90% of patients had bladder outlet
      obstruction (positive predictive value: 90%), we found that PV of 35 ml or more,
      Qmax of 8 ml/sec or less, RU of 110 ml or more, and I-PSS of 30 or more did so.
      Fifty-nine percent of patients met at least one of these criteria. The results
      suggested that 59% of patients with LUTSs had bladder outlet obstruction with a
      90% positive predictive value based on the value of PV, Qmax, RU or I-PSS.

PMID- 11828771
TI  - [A case of asymptomatic urachal cyst in autopsy--histopathological study of
      urachal cyst and review of the literature of 99 cases during a 10 year period in
      Japan].
AB  - Disorders of urachal remnants are common. While urachal cysts are usually
      asymptomatic, infection may mimic a variety of acute abdomen. Here we report a
      very rare case of urachal cyst that protruded in the urinary bladder cavity and
      among 99 accumulated cases, only 4 cases have been reported similar to this case
      characterized by intravesical development from 1990 to 1999. An uninfected
      urachal cyst was found in a 79-year-old male who had died of bile duct carcinoma.
      The cyst showed ovoid protrusion into urinary bladder cavity from the dome (3.5 x
      2.0 x 2.0 cm in size). Histopathologically, the cyst wall was thin and consisted
      of fibrous connective tissue with muscular tissue and peripheral nerve, and lined
      by cuboidal epithelium but no inflammatory cells could be seen. Urachal cysts
      occur in both sexes are affected with equal frequency, and frequently occur in a
      younger population. In clinical symptoms the umbilical manifestations are
      predominant in patients younger than 30 years old, while the bladder
      manifestations are predominant in those older than 30.

PMID- 11828772
TI  - [Primary signet ring cell carcinoma of the urinary bladder: a case report].
AB  - Gross hematuria and urinary frequency caused a 71-year-old man to visit our
      hospital. A non-papillary tumor was identified on the posterior wall of the
      urinary bladder and the pathological diagnosis was signet ring cell carcinoma.
      Upper gastrointestinal endoscopy, computed tomographic scanning, barium enema
      revealed no involvement of other organs. Radical cystectomy and creation of an
      ileal conduit were performed. The histopathological stage was pT4N1M0. Apart from
      subacute ileus, the postoperative course was uneventful. Signet ring cell
      carcinoma of the bladder is a rare entity and we have identified 41 cases in the
      Japanese literature. This tumor usually has a poor prognosis. Our patient is
      currently free from disease at 5 months after the surgery.

PMID- 11828773
TI  - [A case of Sertoli cell tumor of the testis].
AB  - A 24-year-old man was admitted to our hospital with the complaint of a painless
      mass in the left testis. Gynecomastia was not present. The serum levels of alpha
      fetoprotein and human chorionic gonadotropin-beta were not elevated. Ultrasound
      sonography showed a hypoechoic lesion in the left testis. There was no evidence
      of retroperitoneal lymph node enlargement or distant metastasis on computerized
      tomography. With a diagnosis of left testicular tumor, left high orchiectomy was
      done. The tumor measured 10 x 11 mm in size within the testis and was
      histologically diagnosed as benign Sertoli cell tumor. Immunohistochemcal
      analysis revealed negative findings with the tumor markers inhibin, CAM 5.2,
      pancytokeratin, EMA, and PLAP. No adjuvant therapy was performed. Twenty-six
      cases of Sertoli cell tumor of the testis in the Japanese literature are
      reviewed.

PMID- 11828774
TI  - [Transitional cell carcinoma of the ureter with inverted proliferation
      accompanied with papillary bladder tumor: a case report].
AB  - An 85-year-old female was referred to our hospital with chief complaints of right
      flank pain and gross hematuria. Ultrasonography demonstrated right
      hydroureteronephrosis and a thumb head-sized solid mass in the lower third of the
      right ureter. Cystoscopy revealed papillary tumors near the right ureteral
      orifice. Under the preoperative diagnosis of right ureteral tumor and bladder
      tumor, transurethral resection of bladder tumor, right nephroureterectomy and
      partial cystectomy were performed. The gross specimen of the ureter contained a 5
      x 3 x 1 cm, polypoid and smooth-surfaced tumor. The pathological diagnosis of the
      ureteral tumor was transitional cell carcinoma with inverted proliferation, grade
      1 >> grade 2. On the other hand, the bladder tumor was papillary transitional
      cell carcinoma, grade 1. This is a case in which tumor development showed two
      different types.

PMID- 11828775
TI  - [Hyperdense renal cyst associated with papillary adenoma: a case report].
AB  - An abnormal shadow in the chest of a 57-year-old male was detected during a
      medical checkup and careful investigation revealed a left posterior mediastinal
      tumor (neurinoma) and a clearly demarcated homogenous mass with dimensions of 16
      x 12 mm and computed tomographic (CT) value of 79 H.U. in the superior pole of
      the right kidney. The content solution was sticky and blackish-green. Neoplastic
      degenerations of 8 x 4 and 5 x 5 mm were seen in the cyst. Partial nephrectomy,
      which included the cystic section, was conducted and papillary adenoma was
      pathologically diagnosed. Nine years after the operation, the patient is alive
      and neither relapse nor other abnormalities were detected.

PMID- 11828776
TI  - [Retroperitoneal ganglioneuroma: a case report].
AB  - A primary retroperitoneal ganglioneuroma was found incidentally in a 44-year-old
      man. Computed tomography revealed a homogeneous mass just above the right kidney.
      T1-weighted magnetic resonance imaging demonstrated the homogeneous mass, but T2
      weighted imaging revealed a heterogeneous mass with a markedly high intensity
      area. The tumor was resected through a transabdominal approach. The resected
      specimen measured 11 x 9 x 4.5 cm and weighted 270 g. Histological examination
      showed that the lesion was a ganglioneuroma composed of mature ganglion cells and
      nerve fibers.

PMID- 11828777
TI  - [A case of bladder tumor producing granulocyte-colony stimulation factor and
      parathyroid hormone-related protein].
AB  - A 68-year-old woman presented with urinary pain and frequency. Cystoscopy,
      intravenous pyelography and magnetic resonance imaging showed a huge bladder mass
      and hydronephrosis of the left kidney. Transurethral resection of bladder tumor
      (TUR-Bt) was done. Histopathological findings of TUR-biopsy was high grade
      transitional cell carcinoma. Post operatively, the laboratory examination showed
      marked leukocytosis with a maximum of 99,600/mm3 in the peripheral blood and a
      high level of granulocyte colony stimulating factor (G-CSF), 70 pg/ml in the
      serum (normal: less than 9.8 pg/ml). Serum calcium level increased gradually and
      parathyroid hormone-related protein (PTH-rP) revealed high, 8.4 pMol/l (normal:
      less than 0.6 pMol/l). The tumor cells were positive for G-CSF and PTH-rP
      immunohistochemical staining. She died of the disease 46 days after the
      operation. This is the third case of G-CSF and PTH-rP producing bladder tumor in
      the literature.

PMID- 11828778
TI  - [Retroperitoneal dedifferentiated liposarcoma extending into the iliocostal
      muscle and the quadratus lumborum muscle accompanied with bone formation: case
      report].
AB  - A 72-year-old man with back pain on the left side was admitted. Imaging analysis
      revealed a retroperitoneal mass and a mass in the left iliocostal muscle and the
      left quadratus lumborum muscle. The two masses could not be resected en bloc, and
      were resected separately. The clinicopathological findings of these tumors
      revealed dedifferentiated liposarcoma. The primary dedifferentiated liposarcoma
      appeared to have originated from the retroperitoneal space extending into the
      iliocostal muscle and the quadratus lumborum muscle. Then the mass was thought to
      have formed accompanied with osteogenesis.

PMID- 11828779
TI  - Your engineering organization.

PMID- 11828780
TI  - Preparing for the introduction of new technologies: who is going to pay for them?

PMID- 11828781
TI  - The latest innovation in cardiovascular product line development: pocket EKG
      benefiting patients, physicians and payors.

PMID- 11828782
TI  - Conducting conference calls.
AB  - Conducting a conference call essentially is the same as conducting a meeting. The
      author writes the article assuming that the conference calls are audio only (no
      visual interface). Keeping this in mind, the main differences between conducting
      a conference call and conducting a face-to-face meeting are that: 1) the
      participants may live in geographically remote sites, 2) each participant must
      take special care to eliminate noise distractions, and 3) the moderator must keep
      the meeting on track because of the expense associated with using a conference
      bridge. The author shares tips for conducting effective conference calls and two
      conference call checklists designed to facilitate planning, execution, and follow
      up.

PMID- 11828783
TI  - Reducing major identification errors within a deployed phlebotomy process.
AB  - To achieve a patient-focused care environment, many hospitals are moving
      phlebotomy from the laboratory to the nursing units. Although this move has
      benefits, it also can bring an increase in error rates. The Valley Hospital in
      Ridgewood, New Jersey, implemented the BD Dx System patient identification system
      (Becton Dickinson, Franklin Lakes, New Jersey) in an effort to reduce the
      incidence of phlebotomy errors. This article discusses how to identify key
      factors in deploying phlebotomy, to analyze the specimen collection process, to
      set baselines for identification of errors, to identify critical steps in the
      blood collection process for error reduction, and to reduce errors by using the
      new hand-held computer technology for patient and specimen identification.

PMID- 11828784
TI  - Management of point-of-care testing in home health care.
AB  - There have been many strategic changes made in health care to address decreasing
      revenue. One successful strategy is the reduction of the patient's length of
      hospital stay. An outcome of early release from a hospital for some patients is
      that they still require medical assistance. Because of this requirement and the
      increasing aging population, the home health-care industry has been growing. In
      the past 20 years, the home health-care market has seen many changes. The latest
      has been a prospective payment system. This article will describe the past and
      present home health-care markets and future demands. New technologies in home
      health care, such as vital sign technology (telemedicine) and increased numbers
      of waived point-of-care tests, should decrease costs because of fewer visits to
      the home. A pilot study conducted at a home health-care agency in New York
      revealed that 7.3% of home visits offered laboratory testing. The study also
      revealed a 10% return visit to the home to recollect another sample because of
      specimen problems. Costs associated with these return visits are high for home
      health-care agencies, but can be altered via telemedicine technology.
      Telemedicine technology affords the homebound patient to send point-of-care
      testing results to any laboratory for review and storage, allowing the laboratory
      to take control of such testing.

PMID- 11828786
TI  - Management of self: Part one.

PMID- 11828785
TI  - Reference test review by pathology house staff: a cost-containment strategy for
      the clinical laboratory.
AB  - In this era of fiscal responsibility in health care, new strategies are evolving
      to decrease costs in the clinical laboratory. At our institution, one such
      strategy implemented in 1994 consisted of the review by pathology housestaff of
      all send-out tests that cost more than $75 to ensure that an appropriate
      diagnostic test hierarchy was being used and that clerical misorders were
      corrected. Throughout the first fiscal year this system was implemented, the
      annual institutional reference laboratory costs decreased by 10% ($24,784), and
      the number of send-out tests decreased by 23% (2,707 tests). Over the next 2
      fiscal years, the number of sendout tests maintained a level approximately 25%
      lower than the original pre-review level and the reference laboratory costs
      remained 4% to 13% below the pre-review level. A major factor preventing a more
      extensive cost reduction over this time period was the increased frequency of
      orders for expensive molecular studies. Even with the increased use of these
      relatively expensive tests, however, our annual reference laboratory budget and
      number of send-out tests have remained consistently below the levels of 1994.
      Implementation of similar test review systems in other health-care laboratories
      could provide useful budgetary reductions.

PMID- 11828787
TI  - Infectious diseases, confidentiality, and research ethics.

PMID- 11828788
TI  - Common cent$ 4: balanced budgets, deficits, and the price of liberty.

PMID- 11828789
TI  - Business planning: a template for success.
AB  - Because managing a laboratory, or any health-care entity, is as much a business
      as a service, it is important for you to have a good grasp on how you can take
      opportunities from idea conception to implementation to assessment/revision.
      Regardless of the size of your proposed project, you need to consider a number of
      factors, among them: your history and what opportunities you can seize from your
      strengths and weaknesses; the overall business climate; anticipated costs; staff
      involvement; how you will market your project; and what measures to use to
      determine your success. Above all else, you need to set goals, both ultimate and
      intermediate, to instill focus, incentive, and a sense of achievement. The next
      time someone on your staff says, "Why don't we try that?," refer to this Template
      Topic. It can serve as a tool to help you determine whether you should try "that"
      and be the compass that helps guide your efforts.

PMID- 11828790
TI  - Workplace violence: how laboratorians are addressing it; what still needs to be
      done.

PMID- 11828791
TI  - Identification of criteria for a report card to evaluate clinical laboratory
      testing services.
AB  - Report cards increasingly are considered useful to evaluate health-care services.
      Identifying important criteria to stakeholders of clinical laboratory testing
      services is the first step in the development of a report card to evaluate such
      services. The purpose of this study was to identify and examine criteria
      important to two stakeholders of these services. Three phases of data collection
      were conducted: 1) structured telephone interviews, 2) a modified two-round
      Delphi study, and 3) a verification survey of hospital laboratories that purchase
      reference laboratory testing services and Independent Practice Associations
      (IPAs) and Preferred Provider Organizations (PPOs) that purchase clinical
      laboratory testing services. Fifteen of 20 (75%) criteria from the verification
      survey were ranked between very important and essential by hospital laboratory
      and managed care organization purchasers. Eleven of 15 (73.3%) criteria were
      common to both purchaser groups. Six of 11 (54.5%) criteria from the service
      dimension were the most prevalent. In addition to quality, stakeholders consider
      criteria for service, access, and cost important. Combining the criteria
      identified by these two groups serves as the basis of a report card to evaluate
      these services.

PMID- 11828792
TI  - [Can adenosine triphosphate induce maximal hyperemic response in patients with
      impaired coronary microcirculation?: comparison of hyperemic response to
      adenosine triphosphate administered by intravenous and by intracoronary injection
      using Doppler guide wire].
AB  - OBJECTIVES: This study compared the hyperemic responses to adenosine triphosphate
      (ATP) administered by intravenous and by intracoronary injection in patients with
      impaired coronary microcirculation. METHODS: The hyperemic responses to
      intravenous and intracoronary administration of ATP in 107 patients (mean age 63
      +/- 10 years, 77 males, 30 females) with impaired coronary circulation [including
      myocardial infarction (n = 68), cardiomyopath (n = 20) and diabetes mellitus (n =
      11)] were compared by measurement of coronary flow reserve (CFR) using the
      Doppler guide wire. Patients with chest pain syndrome were used as the normal
      controls. The coronary blood flow velocity was measured at rest and during peak
      hyperemic responses to intravenous infusion (150 micrograms/kg/min) and
      intracoronary infusion of ATP (50 micrograms in the left coronary artery, 25
      micrograms in the right coronary artery). The CFR was calculated as the ratio of
      averaged peak velocity during hyperemia to baseline averaged peak velocity.
      RESULTS: The CFR after intravenous administration of ATP (CFRi.v.) was well
      correlated with CFR by intracoronary administration of ATP(CFRic) (r = 0.77, p <
      0.001). However, the CFRi.v. was also inversely correlated with the ratio of
      CFRic to CFRiv (CFRic/i.v.) (r = -0.36, p < 0.001). There were no relationships
      between the changes of hemodynamic parameters(blood pressure and heart rate)
      induced by ATP and CFRic/i.v. A lower CFRi.v. of less than 2.0 provided
      significantly greater CFRic/i.v. than that of CFRiv greater than 2.0.
      CONCLUSIONS: The maximal hyperemic response of coronary artery was not always
      induced by conventional intravenous administration of ATP, especially in patients
      with lower CFR than 2.0. High dose of intravenous ATP and/or intracoronary ATP
      should be administered in patients with lower CFR to attain maximum hyperemia in
      the impaired coronary circulation.

PMID- 11828793
TI  - [New trials for improving diagnostic accuracy of stress technetium-99m
      tetrofosmin single photon emission computed tomography].
AB  - OBJECTIVES: This study evaluated the influence of extra-cardiac accumulation in
      technetium-99m-tetrofosmin myocardial single photon emission computed tomography
      (SPECT) imaging. METHODS: Technetium-99m-tetrofosmin myocardial SPECT was
      performed in 247 patients from 1997 to 1999. To evaluate the sensitivity, 42
      patients with inferior infarction were selected. To evaluate the specificity, 32
      patients with no significant perfusion defect and low pretest likelihood (< 15%)
      of coronary artery disease and 13 patients with normal coronary angiography were
      selected. Firstly, the SPECT raw data were evaluated according to the effects of
      diaphragm and breast, the position and the degree of accumulation of the liver,
      gall bladder and intestine. Then, the myocardial tracer uptake was scored
      semiquantitatively from 0 (normal) to 4 (perfusion defect) in the 13 segments of
      the left ventricle. RESULTS: The specificity was 86.7% and the sensitivity was
      92.8%. Perfusion abnormality of the inferior wall was observed in 6 of 45
      patients with a low pretest likelihood of coronary artery disease. These 6
      patients were classified into the false positive group, and the other 39 patients
      were classified into the true negative group. The liver position and the liver
      accumulation on the stress images were significantly higher in the false positive
      group than in the true negative group (p < 0.001), but only the liver position on
      the rest images was significantly higher in the false positive group (p < 0.001).
      By estimating the defect 1 point lower for the high-positioned liver patients,
      specificity improved from 86.7% to 100% and sensitivity did not change.
      CONCLUSIONS: Inferior perfusion defect on technetium-99m-tetrofosmin myocardial
      SPECT of high-positioned liver patients needs to be evaluated with special
      caution.

PMID- 11828794
TI  - [Clinical significance of plasma concentration of macrophage colony-stimulating
      factor in patients with vasospastic angina].
AB  - OBJECTIVES: The concentration of macrophage colony-stimulating factor (M-CSF), an
      inflammatory cytokine, increases with the progression of coronary lesions, but no
      clinical investigations have evaluated the relationship to coronary vascular
      tone. The present study investigated the relationship between M-CSF and
      vasoreactivity of the coronary arteries in patients with vasospastic angina.
      METHODS: Vasospastic angina (VSA) was characterized by transient chest pain and
      ischemic ST segment changes at rest, or by a positive result in spasm provocation
      testing with acetylcholine. The subjects were 24 patients with stable
      VSA(inactive VSA group) treated on an outpatient basis, 31 VSA patients
      hospitalized with unstable angina (active VSA group), and 13 healthy
      subjects(control group). The sensitivity of determination of plasma M-CSF in
      blood was 40 pg/ml. The levels of this factor in each group were compared. Based
      on the findings of the acetylcholine vasospasm-induction test, patients were
      divided into those with single-vessel vasospasm and those with multivessel
      vasospasm, and, according to the dose of acetylcholine required to induce spasm,
      into high- and low-dose groups. Plasma M-CSF levels in each group were compared.
      RESULTS: Mean plasma M-CSF was 598 +/- 180 pg/ml in the inactive VSA group, 775
      +/- 194 pg/ml in the active VSA group, and 632 +/- 103 pg/ml in the control
      group. The mean plasma M-CSF level in the active VSA group was significantly
      higher than that in the inactive VSA group(p < 0.01). Mean plasma M-CSF level in
      the single-vessel and multivessel vasospasm groups was highest for active VSA
      patients with multivessel vasospasm (872 +/- 173 pg/ml). The relationship with
      the acetylcholine induction dose clarified that plasma M-CSF levels were highest
      in patients with active VSA in the acetylcholine low-dose group (825 +/- 177
      pg/ml, p < 0.001). CONCLUSIONS: Plasma M-CSF concentration reflects the
      vasoreactivity of coronary spasm in the VSA group, and may be an indicator of the
      severity of coronary endothelial dysfunction.

PMID- 11828795
TI  - [So-called "ampulla" cardiomyopathy associated with coronary vasospasm compared
      with acute myocardial infarction showing similar abnormal left ventricular wall
      motion: two case reports].
AB  - So-called "ampulla" cardiomyopathy is characterized by transient abnormal left
      ventricular wall motion showing hypokinesia around the apical area and
      hyperkinesia at the basal area, without any detectable coronary lesion. We
      recently treated a patient with "ampulla" cardiomyopathy (Case 1) and a patient
      with acute myocardial infarction showing similar abnormal left ventricular wall
      motion (Case 2). A 75-year-old female (Case 1) presented with "ampulla"
      cardiomyopathy without coronary lesion. Vasospasm was induced at segment 8 on the
      left anterior descending (LAD) coronary artery by intracoronary administration of
      acetylcholine. A 58-year-old male (Case 2) presented with acute myocardial
      infarction due to occlusion at segment 8 and underwent successful coronary
      reperfusion therapy by direct percutaneous transluminal coronary angioplasty.
      Both Case 1 and Case 2 revelaed similar abnormal left ventricular wall motion,
      with hypokinesia around the apical area and hyperkinesia at the basal area by
      echocardiography, in the acute phase. Furthermore, these two patients showed
      elevated ST segment at both anterior and inferior leads by electrocardiography,
      and markedly reduced uptake of beta-methyl-p-iodophenyl-pentadecanoic acid around
      the apical area in the acute phase by scintigraphy. Interestingly, the LAD
      perfused a relatively wide area including the anterior, apical and part of the
      inferior area of the left ventricle in both patients by coronary angiography. The
      abnormal wall motion of Case 1 disappeared 4 weeks after onset, but that of Case
      2 did not disappear. Although the diagnoses of Case 1 and Case 2 were different,
      abnormal wall motion of these cases might be due to myocardial ischemia due to
      distal LAD lesion. "Ampulla" cardiomyopathy might develop from transient
      myocardial ischemia induced by coronary vasospasm at the distal LAD which
      perfuses a relatively wide area.

PMID- 11828796
TI  - [Heart transplantation for dilated cardiomyopathy possibly caused by fulminant
      acute myocarditis: a case report].
AB  - A 13-year-old boy [corrected] underwent heart transplantation for severe
      congestive heart failure due to dilated cardiomyopathy possibly caused by
      fulminant acute myocarditis. He suddenly suffered chest discomfort and loss of
      consciousness during running, and was referred to a hospital with cardiogenic
      shock. Electrocardiography showed ventricular tachycardia and echocardiography
      revealed severe hypokinesis in an extensive area of the left ventricular wall
      with markedly decreased left ventricular ejection fraction. Percutaneous
      cardiopulmonary support, intraaortic balloon pumping and artificial respiration
      were performed. He suffered from severe heart failure with septic shock and
      bleeding tendency. A left ventricular assist system was fitted at 73 days after
      onset, and he was transferred to the National Cardiovascular Center on the 119th
      hospital day. At 319 days after the left ventricular assist system operation,
      heart transplantation was performed. The etiology and treatment for severe heart
      failure, and several social problems which occurred during care for heart
      transplantation are discussed.

PMID- 11828797
TI  - [Circulating recipient cells contribute to graft coronary arteriosclerosis].
AB  - BACKGROUND: Despite recent advances in immunosuppressive therapy, accelerated
      coronary atherosclerosis remains a major problem in the long-term survival of
      cardiac transplant recipients. However, the pathogenesis of the transplant
      associated atherosclerosis remains largely unknown. METHODS AND RESULTS: The
      origin of the neointimal cells was investigated by heterotopic heart
      transplantation between the wild-type mouse and the ROSA26 mouse that expresses
      LacZ ubiquitously (LacZ-mouse). Coronary arteries of the cardiac allograft
      developed neointimal hyperplasia consisting of alpha-smooth muscle actin-positive
      cells. When a heart from a wild-type mouse was transplanted into a LacZ-mouse,
      most of the neointimal cells expressed LacZ whereas the medial cells were
      negative. In contrast, when a heart from a LacZ-mouse was transplanted into a
      wild-type mouse, most of the neointimal cells were negative for LacZ whereas the
      medial cells expressed LacZ. In situ hybridization of the allografts from female
      to male mice revealed that most of the neointimal cells corresponded to cells
      from the recipients. CONCLUSIONS: Blood cells include progenitors of smooth
      muscle cells, which attach to the graft endothelia, differentiate into smooth
      muscle cells and proliferate, thus contributing to neointima formation. Our
      findings suggest a new therapeutic strategy that involves targeting of homing,
      differentiation and proliferation of putative smooth muscle progenitor cells to
      prevent proliferative vascular diseases.

PMID- 11828798
TI  - [Autoantibodies against sarcolemmal Na-K-ATPase in patients with dilated
      cardiomyopathy: autoimmune basis for ventricular arrhythmias in patients with
      congestive heart failure].
AB  - BACKGROUND: Autoimmunity is one of the mechanisms of pathogenesis of idiopathic
      dilated cardiomyopathy (DCM) as well as virus infection and genetic
      predisposition. Autoantibodies against sarcolemmal Na-K-ATPase may be involved in
      the development of ventricular tachycardia and cardiac sudden death in patients
      with DCM. METHODS AND RESULTS: By using enzyme-linked immunosorbent assay,
      autoantibodies were detected in 26% patients with DCM and in 2% age-matched
      control subjects. Na-K-ATPase activity in the presence of patient IgG was lower
      in patients with autoantibodies than without autoantibodies, but there was no
      difference in the control subjects. Western blots showed that autoantibodies
      recognized the alpha-subunit of Na-K-ATPase, and 3H-ouabain bindings in the
      presence of patient IgG showed that the dissociation constant was higher in
      patients with autoantibodies than without autoantibodies, although maximal
      binding sites were similar between the two groups. No difference existed between
      subjects with regard to age, sex, New York Heart Association functional class,
      cardiac function, or neurohormone levels, except for plasma norepinephrine which
      was higher in patients with autoantibodies than without autoantibodies,
      Ventricular arrhythmias were more common in patients with autoantibodies than
      without autoantibodies, and multiple logistic regression analysis demonstrated
      that the presence of autoantibodies, but not plasma norepinephrine, was an
      independent predictor for the occurrence of ventricular tachycardia. Cardiac
      sudden death was independently predicted by the presence of autoantibodies, as
      well as poor systolic function. CONCLUSIONS: Patients with DCM express
      autoantibodies against sarcolemmal Na-K-ATPase, and these autoantibodies could be
      responsible for the electrical instability in some patients.

PMID- 11828799
TI  - [Silent and clinically overt stroke in older Japanese subjects with white-coat
      and sustained hypertension].
AB  - BACKGROUND: Whether white-coat hypertension in older subjects is a benign
      condition or is associated with an increased risk for stroke remains uncertain.
      White-coat hypertension as a risk factor for stroke was investigated in relation
      to silent cerebral infarct in the older Japanese population. METHODS: The
      prognosis for stroke was studied in 958 older Japanese subjects [147
      normotensives (NT), 236 white-coat hypertensives (WCHT), and 575 sustained
      hypertensives (SHT)] in whom ambulatory blood pressure monitoring was performed
      in the absence of antihypertensive treatment. Silent cerebral infarct was also
      assessed using brain magnetic resonance imaging in 585 subjects (61%). RESULTS:
      Silent cerebral infarcts were found in 36% of NT (n = 70), 42% of WCHT (n = 154),
      and 53% of SHT (n = 361), and multiple silent cerebral infarcts(presence of > or
      = 2 silent cerebral infarcts) were found in 24% of NT, 25% of WCHT, and 39% of
      SHT. During a mean 42-month-follow-up period, clinically overt strokes occurred
      in 62 subjects [NT 3(2.0%), WCHT 5(2.1%), SHT 54(9.4%)], with 14 fatal cases [NT
      1(0.7%), WCHT 0(0%), SHT 13 (2.3%)]. Cox regression analysis showed that age (p =
      0.0001) and SHT [RR(95% confidence interval): 4.3 (1.3-14.2), p = 0.018] were
      independent stroke predictors, whereas WCHT was not significant. Adding
      presence/absence of silent cerebral infarct at baseline into this model, the RR
      (95% confidence interval) for silent cerebral infarct was 4.6 (2.0-10.5) (p =
      0.003), and that of SHT was 5.5 (1.8-18.9) vs WCHT (p = 0.004) and 3.8 (0.88
      16.7) vs NT (p = 0.07). CONCLUSIONS: The incidence of stroke in WCHT is similar
      to that of NT, and one fourth the risk in SHT in older subjects. Although silent
      cerebral infarct is a strong predictor of stroke, the difference in stroke
      prognosis between SHT and WCHT was independent of silent cerebral infarct. It is
      clinically important to distinguish WCHT from SHT even after assessment of target
      organ damage in the elderly.

PMID- 11828800
TI  - [Amelioration of ischemia- and reperfusion-induced myocardial injury by the
      selective estrogen receptor modulator, raloxifene, in the canine heart].
AB  - BACKGROUND: 17 beta-estradiol reduces myocardial infarct size which is mediated
      by nitric oxide (NO) and the opening of Ca (2+)-activated K+ (KCa) channels.
      Raloxifene, a selective estrogen receptor modulator, demonstrates acute coronary
      artery vasorelaxing effects. Whether raloxifene reduces ischemia/reperfusion
      injury and what mechanisms are involved in the cardioprotective effects were
      investigated. METHODS: Infarct size was measured in open-chest dogs following
      occlusion of the left anterior descending coronary artery for 90 min and
      subsequent reperfusion for 6 hr. The incidence of ventricular fibrillations
      during reperfusion period was also observed. Infusion of raloxifene and/or other
      drugs into the left anterior descending coronary artery was initiated 10 min
      before coronary occlusion and continued until 1 hr after reperfusion started
      without an occlusion period. RESULTS: Infarct size was reduced in the raloxifene
      (5 micrograms/kg/min) group compared with the control group (6.8 +/- 4.2% vs 40.9
      +/- 3.9% of the area at risk, p < 0.01). Either NG-nitro-L-arginine methyl ester,
      the inhibitor of NO synthase (infarct size: 22.8 +/- 5.4%, p < 0.05 vs raloxifene
      or the control) or charbdotoxin, the blocker of KCa channels (infarct size: 23.5
      +/- 5.1%, p < 0.05 vs raloxifene or the control), partially attenuated the
      infarct size-limiting effect, and combination of both agents completely abolished
      the effect (infarct size: 37.7 +/- 5.8%). The incidence of ventricular
      fibrillations was also less in the raloxifene group than in the control group(11%
      vs 44%, p < 0.05). CONCLUSIONS: Raloxifene reduces myocardial infarct size and
      the incidence of ventricular fibrillations by NO- and the opening of KCa channels
      dependent mechanisms in canine hearts.

PMID- 11828801
TI  - [Up-regulation of inositol 1, 4, 5-trisphosphate receptor expression in atrial
      tissue in patients with chronic atrial fibrillation].
AB  - BACKGROUND: Abnormal intracellular Ca2+ homeostasis occurs in chronic atrial
      fibrillation(AF). The intracellular Ca2+ concentration is regulated by ryanodine
      and inositol 1,4,5-trisphosphate (IP3) receptors. Changes occur in ryanodine
      receptors in atrial tissue from patients in chronic AF. Whether AF patients have
      alterations in atrial IP3 receptors was investigated. METHODS: IP3 receptor
      expression was analyzed in the right atrial myocardium from 13 mitral valvular
      disease (MVD) patients with AF (MVD/AF), 5MVD patients with normal sinus
      rhythm(MVD/NSR), and 8 control patients with NSR(tissue obtained during coronary
      artery bypass surgery). Hemodynamic and echocardiographic data were obtained
      preoperatively, and an immunohistochemical study was performed on the atrial
      tissue. RESULTS: The relative expression level of IP3 receptor protein was
      significantly greater in MVD/AF (0.75 +/- 0.26) than in MVD/NSR (0.42 +/- 0.13, p
      < 0.01), and both were significantly above the control value (0.14 +/- 0.08). The
      relative expression level of IP3 receptor mRNA was significantly greater in
      MVD/AF(0.028 +/- 0.008) than in control subjects (0.015 +/- 0.004, p < 0.01), but
      MVD/AF patients did not differ from MVD/NSR (0.020 +/- 0.006) patients. The
      relative expression levels of IP3 receptor protein and mRNA were higher in
      patients with left atrial dimension > or = 40 mm, pulmonary capillary wedge
      pressure > or = 10 mmHg, and right atrial pressure > or = 5 mmHg. IP3 receptors
      were overexpressed in the cytosol and at the nuclear envelope of atrial myocytes
      in MVD. CONCLUSIONS: Since chronic mechanical overload of the atrial myocardium
      increases IP3 receptor expression, especially in patients with chronic AF, up
      regulation of IP3 receptors may be important in modulating intracellular Ca2+
      homeostasis and initiating and/or perpetuating AF.

PMID- 11828802
TI  - Cardiovascular imaging in-a-month. A 68-year-old man with renal artery stenosis.

PMID- 11828803
TI  - Most M+C plans see minimal cap increases for 2002.

PMID- 11828804
TI  - Utilization, costs of substance abuse growing, researchers warn.

PMID- 11828805
TI  - Is Medicare risk adjustment formula missing its mark?

PMID- 11828806
TI  - PHO improves cap rates, data collection to manage risk.

PMID- 11828807
TI  - Teaching hospitals need specialized surgical benchmarks.

PMID- 11828808
TI  - Analysis of plan administrative costs offers terrific insights.

PMID- 11828809
TI  - The psychiatric consequences of trauma.
AB  - Trauma can have marked and sustained psychological effects. Those at high risk
      thereof can be identified, and effective treatments are available. This review
      provides guidelines for the effective management of the psychiatric sequelae of
      trauma.

PMID- 11828810
TI  - Changing scene in hepatitis B serology interpretation.
AB  - Serological tests have been used in the diagnosis of hepatitis B virus (HBV)
      infection since the virus was first discovered. Advances in molecular biology and
      improvements in the understanding of HBV virology have changed the scene of
      hepatitis B serology interpretation.

PMID- 11828811
TI  - Long-acting beta 2-agonists in chronic obstructive pulmonary disease.
AB  - Until recently, the use of long-acting beta 2-agonists in chronic obstructive
      pulmonary disease has been understated. There is now evidence that they may offer
      benefits beyond bronchodilation. This article reviews the management of chronic
      obstructive pulmonary disease and looks at the place of long-acting beta 2
      agonists as a first-line treatment option.

PMID- 11828812
TI  - Hypoplastic left heart syndrome: diagnosis and management.
AB  - The prognosis of hypoplastic left heart syndrome has improved dramatically in
      recent years with advances in reconstructive surgery. Many cases are now
      diagnosed antenatally, allowing parents time to make informed decisions about
      treatment options.

PMID- 11828813
TI  - Advances in the management of CSF rhinorrhoea.
AB  - Cerebrospinal fluid fistulae are under-diagnosed, difficult to locate and often
      clinically silent. They are potentially lethal and carry a long-term cumulative
      risk of meningitis. They should be fully investigated and treated aggressively.
      Current endoscopic techniques combined with intrathecal fluorescein dye enable
      most defects to be located and sealed with minimal morbidity.

PMID- 11828814
TI  - Bladder and renal stones: management and treatment.
AB  - The prevalence of renal tract calculi in the population is such that patients may
      present acutely not only to urologists, but in the setting of any medical
      specialty. This article aims to enable all practitioners to be able to recognize
      the condition and instigate early investigation and management before referring
      to the urologist for definitive treatment.

PMID- 11828815
TI  - Why is xenon not more widely used for anaesthesia?

PMID- 11828816
TI  - Diagnosis and immediate care of fractured neck of femur.

PMID- 11828817
TI  - Effects of the Omagh bombing on medical staff working in the local NHS trust: a
      longitudinal survey.
AB  - This article investigates post-traumatic stress disorder (PTSD) symptoms reported
      by doctors working in the aftermath of the Omagh bombing. Doctors responding to
      surveys 4 and 17 months after the incident reported the lowest symptom levels
      compared with other health service staff, with only 12% (2) above PTSD threshold
      at 17 months. Junior doctors had higher mean PTSD scores than seniors, although
      numbers are too small to test significance. Possible explanations are discussed
      and recommendations made.

PMID- 11828819
TI  - Cloning cells: it's big business (but is it right?).

PMID- 11828818
TI  - Tophaceous podagra: ultrasound diagnosis.

PMID- 11828820
TI  - Undiagnosed sinusitis leading to orbital cellulitis.

PMID- 11828821
TI  - Frontal osteomyelitis: a serious complication of sinusitis.

PMID- 11828822
TI  - Making paediatric oncological research relevant.

PMID- 11828823
TI  - Musical management of Parkinson's disease.

PMID- 11828824
TI  - Infectious mononucleosis.

PMID- 11828825
TI  - The current state of cartilage transplantation.

PMID- 11828826
TI  - Obtaining consent in the elderly patient.

PMID- 11828827
TI  - Traumatic brain injury: assessment and management.
AB  - Suspected traumatic brain injury is a common presenting problem for emergency
      department staff. Sorting out who needs to have a computed tomography scan, who
      should be admitted and who should be followed up can be difficult. A framework
      for making these decisions is provided in this article.

PMID- 11828828
TI  - Use of proportional reporting ratios (PRRs) for signal generation from
      spontaneous adverse drug reaction reports.
AB  - BACKGROUND: The process of generating 'signals' of possible unrecognized hazards
      from spontaneous adverse drug reaction reporting data has been likened to looking
      for a needle in a haystack. However, statistical approaches to the data have been
      under-utilised. METHODS: Using the UK Yellow Card database, we have developed and
      evaluated a statistical aid to signal generation called a Proportional Reporting
      Ratio (PRR). The proportion of all reactions to a drug which are for a particular
      medical condition of interest is compared to the same proportion for all drugs in
      the database, in a 2 x 2 table. We investigated a group of newly-marketed drugs
      using as minimum criteria for a signal, 3 or more cases, PRR at least 2, chi
      squared of at least 4. FINDINGS: The database was used to examine retrospectively
      15 drugs newly-marketed in the UK, with the highest levels of ADR reporting. The
      method identified 481 signals meeting the minimum criteria during the period 1996
      8. Further evaluation of these showed that 70% were known adverse reactions, 13%
      were events which were likely to be related to the underlying disease and 17%
      were signals requiring further evaluation. IMPLICATIONS: Proportional reporting
      ratios are a valuable aid to signal generation from spontaneous reporting data
      which are easy to calculate and interpret, and various refinements are possible.

PMID- 11828829
TI  - Construction of the Korea Elderly Pharmacoepidemiologic Cohort: drug utilization
      review of cephalosporins in geriatric inpatients.
AB  - We performed a cohort-based pharmacoepidemiologic study in order to evaluate the
      pattern of cephalosporin prescriptions in elderly inpatients in Korea. The Korea
      Elderly Pharmacoepidemiologic Cohort was composed of a geriatric population of
      beneficiaries of the Korea Medical Insurance Corporation residing in Busan in
      1993. The cohort consisted of 23,649 members, comprising 15,221 women (64.4%) and
      8428 men (35.6%). The study population for drug utilization review consisted of
      those cohort members who were admitted into hospitals during the period January
      1993 through December 1994. The number of hospitalized patients was 4262,
      comprising 2631 women (61.7%) and 1681 men (38.3%). The trend of cephalosporin
      prescriptions over the 2-year period showed that the use of second and third
      generation cephalosporins increased relative to the use of first generation. The
      use of cephalosporins combined with other antibiotics was found to occur in 22.8%
      aminoglycosides (76.7%) and quinolones (17.1%) being the most common antibiotics
      combined with cephalosporins. Our result demonstrates an increase in the
      prescription of second and third generation cephalosporins in Korea, which has
      implications not only for the elderly population but also for the total
      population because of the impact on health care costs and the potential for the
      emergence of antimicrobial resistance.

PMID- 11828830
TI  - Surrogate endpoints: the debate goes on.

PMID- 11828831
TI  - The use of surrogate endpoints in clinical trials: focus on clinical trials in
      cardiovascular diseases.
AB  - Surrogate endpoints include a wide range of laboratory or physical measurements
      used in clinical trials as a substitute for meaningful clinical endpoints that
      directly assess effects of the intervention(s) tested on mortality and/or
      morbidity. These surrogate endpoints are frequently employed in clinical trials
      and when used judiciously, can accelerate and focus the study of new therapies
      and can greatly enhance our understanding of their mechanisms of action. The
      current review provides a definition of surrogate endpoints, proposes practical
      criteria for establishing their validity, outlines some of the advantages,
      disadvantages and specific statistical considerations associated with their use
      in clinical trials and attempts also to highlight drug approval issues associated
      with the use of these endpoints. A number of examples are also provided related
      to the use of surrogate endpoints in clinical trials with special emphasis on
      their use in cardiovascular medicine.

PMID- 11828832
TI  - Topical beta-blockers in patients with co-existing conditions: is this a cause
      for concern?

PMID- 11828834
TI  - Drug switching patterns among patients taking non-steroidal anti-inflammatory
      drugs: a retrospective cohort study of a general practitioners database in the
      United Kingdom.
AB  - OBJECTIVE: To examine the frequency and determinants of switching between
      different non-steroidal anti-inflammatory drugs (NSAIDs) and the relationship
      with co-prescription of gastro-protective drugs (GPDs). DESIGN: This was an
      analysis of 30,654 patients receiving a total of 209,140 NSAID prescriptions in
      the UK from 1 January 1997 to 31 December 1998 identified through the MediPlus
      database. Analyses examined switching, repeat, termination and GPD co
      prescription rates in new and continuing takers according to age and sex.
      RESULTS: Each patient received an average of 6.8 prescriptions in the year of
      study. Of the prescriptions 72.2% were for one of three NSAIDs, ibuprofen,
      diclofenac, or naproxen, and 7.2% of prescriptions were for fixed combination
      products of an NSAID plus a gastroprotective drug. At least 16.0% of continuing
      takers, and 28.5% of new takers switched to another NSAID in the review period.
      On average, new patients switched more frequently than continuing patients (0.39
      switches/patient/year versus 0.23 switches/patient/year, p < 0.001). Switching
      between NSAIDs decreased with age and was less common in women (p < 0.05).
      Switching was associated with a 24% and 33% increased probability of GPD
      prescription in new and continuing takers, respectively. DISCUSSION: The
      frequency of switching, and of GPD co-prescription at switching, suggest that
      dissatisfaction with NSAIDs is frequent, and that gastrointestinal intolerance is
      a common feature of this dissatisfaction.

PMID- 11828833
TI  - Co-prescribing of medications used to treat obstructive lung disease, congestive
      heart failure and depression among users of topical beta blockers: estimates from
      three US Veterans Affairs Medical Centers.
AB  - PURPOSE: To estimate the frequency of co-prescribing of medications used to treat
      obstructive lung disease, congestive heart failure, and depression among US armed
      service veterans for whom topical beta blockers (TBB) have been prescribed.
      METHODS: Prescription data from the computerized medical record systems of three
      US Veterans Affairs Medical Centers were obtained during Fall 1999 to identify
      patients for whom active prescriptions existed for TBB and/or drugs commonly used
      to treat obstructive lung disease, congestive heart failure, and depression.
      RESULTS: Among TBB users, the estimated co-prescribing rate of medications used
      to treat obstructive lung disease is in the range of 7.8-9.7%, of medications
      used to treat congestive heart failure is in the range of 4.3-25.1%, and of
      medications used to treat depression is in the range of 8.8-11.7%. The total
      number of TBB users with a concurrent prescription for one or more of the
      conditions studied was in the range of 30.2-45.7%. CONCLUSIONS: Since TBB may
      cause systemic side-effects and thus potentially cause exacerbations of selected
      chronic conditions, it is important for researchers and prescribers to be aware
      of the frequency with which their patients with glaucoma may have other
      concomitant conditions.

PMID- 11828835
TI  - Antidepressant medication and suicide in Sweden.
AB  - OBJECTIVE: To explore a possible temporal association between changes in
      antidepressant sales and suicide rates in different age groups. METHODS: A time
      series analysis using a two-slope model to compare suicide rates in Sweden before
      and after introduction of the selective serotonin reuptake inhibitors, SSRIs.
      RESULTS: Antidepressant sales increased between 1977-1979 and 1995-1997 in men
      from 4.2 defined daily doses per 1000 inhabitants and day (DDD/t.i.d) to 21.8 and
      in women from 8.8 to 42.4. Antidepressant sales were twice as high in the elderly
      as in the 25-44-year-olds and eight times that in the 15-24-year-olds. During the
      same time period suicide rates decreased in men from 48.2 to 33.3 per 10(5)
      inhabitants/year and in women from 20.3 to 13.4. There was significant change in
      the slope in suicide rates after the introduction of the SSRI, for both men and
      women, which corresponds to approximately 348 fewer suicides during 1990-1997.
      Half of these 'saved lives' occurred among young adults. CONCLUSION: We
      demonstrate a statistically significant change in slope in suicide rates in men
      and women that coincided with the introduction of the SSRI antidepressants in
      Sweden. This change preceded the exponential increase in antidepressant sales.

PMID- 11828836
TI  - Benzodiazepine use in patients hospitalized in a department of internal medicine:
      frequency and clinical correlates.
AB  - PURPOSE: Misuse and overuse of benzodiazepines (BZD) are common. Several studies
      have shown that benzodiazepines are frequently used in hospitalized patients, but
      fewer studies have been conducted to investigate whether BZD use increases during
      the hospital stay or whether patients have already taken BZD before admission.
      OBJECTIVE: To assess the prevalence of benzodiazepine use in hospitalized
      patients and to determine characteristics associated with this use. METHODS:
      Prospective study over a 4-month period based on all admissions to a department
      of internal medicine. The main outcome was the prevalence of benzodiazepine use
      at admission, during hospital stay and at discharge. RESULTS: Of 444 patients
      admitted, 147 (33%) used at least one benzodiazepine which was in 75% of the
      cases, short-elimination half-life BZD used as hypnotic. Of 105 (23.6%) patients
      using BZD at admission, 23 (5.2%) stopped BZD during hospital stay or when
      leaving hospital. The in-hospital prevalence of BZD use was 30% (133 patients).
      In 28 (6.3%) patients without BZD at baseline, BZD was introduced during the
      hospital stay then stopped at discharge in 18 (4%) patients. The prevalence of
      BZD use at discharge was 23.9% (106 patients). In multivariate analyses, BZD use
      was significantly associated with number of drugs taken during hospitalization
      (OR: 1.13; 95% CI: 1.03-1.24), and current neuropsychiatric diseases (OR: 2.12;
      95% CI: 0.86-5.23), but not with gender, age or length of stay. CONCLUSION:
      Prevalence of BZD use appeared to be fairly high among hospitalized patients.
      There were very few new BZD users during hospital stay, most of whom were stopped
      at discharge. Most treatments were started before hospital, and continued during
      and after hospital stay without clear reevaluation.

PMID- 11828838
TI  - Estimation of incidence and prevalence of Parkinson's disease in the elderly
      using pharmacy records.
AB  - PURPOSE: We determined the prevalence and incidence of Parkinson's disease among
      persons aged 55 years and older in pharmacy records. METHODS: Data came from the
      PHARMO database which includes information on drug dispensing for all residents
      of six Dutch cities. We selected all persons aged 55 years and older who had used
      antiparkinsonian drugs, and calculated a chance for having Parkinson's disease
      with use of a previously validated logistic regression model. We used a cut-off
      of 0.5 (sensitivity 62%, positive predictive value 92%). Prevalence was estimated
      on the first Wednesday of October 1997, incidence on the first Wednesday of
      October 1993 until 1997. A patient was incident, if the first prescription for an
      anti-parkinsonian drug was dispensed at least 180 days after entry into PHARMO.
      Prevalence and incidence were standardized to the Netherlands population of 1
      January 1998. The prevalence was adjusted for the sensitivity and positive
      predictive value of the model. RESULTS: The unadjusted prevalence (per 100,000)
      for those aged 55-64 years was 111, 65-74 years 598, 75-84 years 1551 and for
      persons aged 85 years and older 1847. The adjusted and standardized prevalence
      was 970 per 100,000 (95% confidence interval 869 to 1071). The incidence (per
      100,000 person years) for persons aged 55-64 years was 12, 65-74 years 108, 75-84
      years 257 and for persons aged 85 years and older 247. The standardized incidence
      was 109 per 100,000 person years (96 to 121). CONCLUSIONS: Prevalence and
      incidence were in range with the literature. Pharmacy records therefore seem to
      be a useful tool for continuous monitoring of incidence and prevalence of
      Parkinson's disease.

PMID- 11828837
TI  - Troglitazone (Rezulin) and hepatic injury.
AB  - PURPOSE: Analyze US rates of reported severe liver disease for the oral
      hypoglycemic agent troglitazone from March 1997 through February 2000 and the
      possible effects of publicity on reporting. METHODS: The number of troglitazone
      reports with liver failure and or hospitalization with jaundice or
      hyperbilirubinemia, made to the FDA and/or Parke-Davis are used as numerators.
      The denominators are numbers of patients and person-time estimates of exposure.
      Additionally, the amount of publicity about troglitazone during its marketing is
      quantified. RESULTS: Approximately 1.92 million patients were treated with
      troglitazone from March 1997 through the end of February 2000 resulting in 1.6
      million person-years of exposure. Reports of 83 cases of liver failure associated
      with troglitazone were received (1 in 23,000 patients or 1 in 20,000 person
      years). Of the 83 cases, only 49 (59%) were classified by a hepatologist to be
      'possibly' or 'probably' attributed to troglitazone. For the first, second, and
      third years of marketing, rates of reported hepatic failure per 100,000 person
      years exposure to troglitazone were 8.3, 5.3, and 2.7 respectively. Rates of
      reported liver disease involving hospitalizations with mention of jaundice and
      hyperbilirubinemia per 100,000 person-years were 16.0, 6.1, and 3.6 respectively
      for these years. During the 3-year marketing history of troglitazone, there were
      470 lay press and 158 medical literature articles with mentions of hepatotoxicity
      for the drug. CONCLUSIONS: Rates of reported severe liver disease declined
      substantially during the second and third years of marketing of troglitazone. The
      decline followed increasingly stringent requirements for liver function test
      monitoring and may have been due to improved patient selection and management as
      a result of the widely publicized association between troglitazone and
      hepatotoxicity.

PMID- 11828839
TI  - Generic substitution--issues relating to the Australian experience.

PMID- 11828840
TI  - Current status of the drug safety monitoring system in Korea.

PMID- 11828841
TI  - Pharmacoepidemiology and drug safety.

PMID- 11828842
TI  - [Hearing impairment in the plastics industry workers exposed to styrene and
      noise].
AB  - Styrene exerts ototoxic effect in animals, and the combined exposure to this
      solvent and noise produces a synergistic effect relative to the isolated exposure
      to noise. However, there is a lack of reliable evidence that chronic occupational
      exposure to styrene is ototoxic to humans. Neither has been documented its
      additive effect with noise. The present study was aimed to assess hearing
      impairment and the risk of hearing loss in workers exposed to both styrene and
      noise. The study group included 72 male workers occupationally exposed to styrene
      in the plastics industry. The results were compared with two control groups,
      matched by age, gender and personal traits: one group composed of 82 male workers
      employed in a printing house and exposed only to noise at the levels almost twice
      as high as those observed in the group exposed to styrene and noise, and the
      other consisted of 65 male workers exposed neither to solvents nor to noise at
      workplace. In the group exposed to styrene and noise, significantly increased
      average hearing loss, as compared to both control groups, was found at all
      frequencies (1-8 kHz). The risk of hearing loss in the group exposed to styrene
      and noise was seven times higher (RR: 6.6; 3.0-15.9) than in the non-exposed
      group, and four times higher (RR: 4.0; 1.8-9.1) than in when workers exposed only
      to noise. However, no relationship could be observed between the amount of
      styrene exposure and hearing impairment, taking account of the confounding effect
      of noise and age. The results of the study suggest that the exposure to solvent
      mixtures with styrene as a basic component may exert additional, to noise,
      adverse effect on the auditory organ.

PMID- 11828843
TI  - [Tinnitus in noise-induced hearing impairment].
AB  - The analysis of the epidemiological data indicates that exposure to noise is
      widespread and it is one of the most common causes of tinnitus, estimated at
      about 20.7% according to Hazell; 28% according to Axelsson; and 42% according to
      Palmer. Bearing in mind the scantiness of reliable data on the incidence and
      nature of tinnitus in persons exposed to industrial noise, and especially the
      need for the objectivity of this subjective symptom, the authors have decided to
      undertake the study aimed at assessing the interrelation between tinnitus, the
      magnitude and kind of hearing impairment, and otoacoustic emission. The study
      group included 191 persons aged 42.5 +/- 7.6 years (range, 25 to 65),
      occupationally exposed to noise at the levels of 88-92 dB(A) for 26.9 +/- 4.6
      years (range, 9 to 30) who had reported hearing disorders and tinnitus. The
      control group, matched by similar age and duration of employment, consisted of 80
      persons with perceptive hearing impairment induced by industrial noise who had
      not complained of tinnitus. The results of the study revealed that in 59.7% of
      the study subjects, noise proved to be one of the most probable factors
      responsible for the development of tinnitus. The presence of tinnitus was found
      in 22.5% and in 46% of the study subjects after 10 years and 11-20 years of noise
      exposure, respectively. In 95.8% of workers, tinnitus was associated with hearing
      loss, and only in 4.2% of cases it occurred in ears with normal hearing. In
      persons exposed to noise, tinnitus was most frequently (59.2%) bilateral and
      permanent. Following the audiologic examinations, verified by objective
      audiometry (tympanometry, ABR), cochlear hearing impairment was found in 68.6%;
      retrochochlear in 8.37%; mixed and other forms of impairment, e.g. presbyacousis,
      in 19.4% of subjects. The audiologic assessment of tinnitus demonstrated that in
      62.3% of persons, tinnitus occurred at high frequencies and correlated with the
      magnitude of hearing impairment in the tonal audiogram. The tinnitus intensity
      ranged between 10-15 dB and 45 dB. In 40.3% of those under study, noise was not
      the only tinnitus-risk factor. In this group of persons, the presence of
      predisposing diseases was also observed, e.g. hypertension, diabetes,
      atherosclerosis, disturbed lipid metabolism and other etiologic factors that
      might have impact on the tinnitus incidence, ototoxic drugs, for example. The
      measurements of evoked otoacoustic emission (EOAE and DPOAE) revealed in 58.63%
      of persons significant differences (p < 0.01) in the amplitude and spectrum of
      EOAE in the ears with tinnitus as compared to the ears without tinnitus with a
      similar hearing threshold. Whereas in 27.74% of subjects, no differences in the
      EOAE measurements in the ears with or without tinnitus were observed. The results
      of DPOAE measurements showed in 62% of subjects significant differences in DP
      grams in the ears with tinnitus as compared to the ears without tinnitus (p <
      0.01). Interestingly, the differences in measurements of both types of evoked
      emissions (EOAE and DPOAE), expressed by the lowered amplitude, narrowed
      spectrum, reduction of emission or its complete fading in a limited area of high
      frequencies, were demonstrated in the ears with tinnitus only in retrocochlear
      hearing impairment, as compared to those free from tinnitus. The evaluation of
      the EOAE and DPOAE measurements seems to prove that this method may be useful in
      assessing the contribution of the cochlear mechanisms to the incidence of
      tinnitus and in distinguishing between tinnitus generated in cochlea and tinnitus
      with the source at other levels of the hearing organ or beyond it. Our study
      failed to determine the interrelation between tinnitus and spontaneous emissions
      as the emission was registered only in about 12% of persons exposed to noise,
      including 2% of those with normal hearing.

PMID- 11828845
TI  - [Exposure to VHF and UHF electromagnetic fields among workers employed in radio
      and TV broadcast centers. I. Assessment of exposure].
AB  - Nowadays, radio and television have become one of the areas of the human
      technical activity that develops most rapidly. Also ultra-short waves of VHF (30
      300 MHz) and UHF (0.3-3 GHz) bands have proved to be the most important carriers
      of radio and TV-programs. In Poland, a network of radio and TV broadcast centers
      (RTCN) with high (over 200 m) masts was set up in the 1960s and 1970s. These
      centers concentrate the majority of stations broadcasting national and local
      programs (for areas within the RTCN range). At present, the RTCN established
      several decades ago are equally important. The assessment of the exposure to
      electromagnetic fields among workers of multi-program broadcast stations is
      complicated and feasible only to a certain degree of approximation because of
      changing conditions of exposure in individual stations during their long history,
      resulting from the changing numbers and types of transmitters installed. In this
      work, the method of retrospective estimation of exposure dose is described, and
      the results of the assessment carried out at three kinds of typical RTCN are
      discussed. The results of the analysis indicate that the workers of RTCN are
      exposed primarily to electromagnetic fields of VHF and UHF bands, but this
      exposure may be considered as admissible, hence it should not exert an adverse
      effect on the workers' health.

PMID- 11828844
TI  - [Standardized new method for measuring vibration perception].
AB  - The examination of the vibration perception is one of the basic measurements
      applied in the evaluation of the peripheral neuropathies in hand-arm vibration
      syndrome (HAVS) The detailed guidelines on how this kind of examinations should
      be performed, presented in the 1998 ISO standard, differ substantially from those
      currently binding in Poland. The aim of this study was to standardize the method
      of vibration perception measurements, taking account of the parameters consistent
      with the ISO recommendations, such as algorithm (stimulus presentation method),
      vibration frequency, the size and contact force of vibrating probe, as well as
      the comparison of the results obtained by means of both methods (ISO-recommended
      method and standard Polish method). It was found that the algorithm change
      (ascending method replaced by Bekesy's technique, recommended by ISO) did not
      affect the of the vibration perception thresholds values within the wide range of
      frequencies (32-500 Hz), whereas the decreased size of probe, pressed with
      smaller contact force, resulted in significantly higher values of perception
      thresholds within the frequency range of 125-400 Hz. The comparison of the
      outcomes of the ISO-recommended and Polish standard methods revealed that the
      perception thresholds did not differ at the frequency of 125 Hz, but at the
      frequencies of 250 and 400 Hz, the ISO-recommended method produced higher values.
      Moreover, at the frequencies ranging from 125 to 400 Hz, the results of the
      perception threshold measurements, taken several times in the same persons
      (intrasubject variability) by means of both methods, were more scattered. It was
      revealed that the measurements at the frequency range of 4-125 Hz should be
      included in the vibration perception examinations, and the certification of the
      ability to work in the conditions of exposure to hand-arm vibration should be
      based on their results. It is also essential that in the standard examination, a
      smaller vibratory probe (phi = 5 mm) and lighter contact force (0.1 N) than those
      currently used, should be applied.

PMID- 11828846
TI  - [Mental health status in workers: the results based on the Munich version of the
      International Composite Diagnostic Interview (M-CIDI)].
AB  - The present study was undertaken with two objectives. First, to assess the
      prevalence of mental health disorders among primary health patients. All the
      subjects under study (n = 170) had at least part time job. The mental health
      status of the patients was assessed on the basis of standardized psychiatric
      interview, M-CIDI (computer version). More than a half of the study population
      (51.8%) had at least one diagnosis of mental health disorder. The following
      disorders were most common in the group: neurotic, stress-related and somaform
      disorders (32.9%), mental and behavioral disorders due to psychoactive substance
      use (26.5; 11.8%--nicotine dependence) and mood (affective) disorders (16.5%).
      Two or more mental health disorders were diagnosed in every second person.
      Second, to evaluate the usefulness of M-CIDI as a tool for assessing psychiatric
      problems. Taking into account the research experience, M-CIDI is a valuable and
      easy to use diagnostic tool for detecting mental health disorders. The most
      important advantage of this instrument relies on its standardization that allows
      to carry out examinations even by persons who have no knowledge of psychiatry.
      The computer version of the M-CIDI is little time-consuming, simple and easy to
      operate as compared to the paper-pencil version It also has a quick access to the
      data base with the stored information about patients and their diagnoses.

PMID- 11828847
TI  - [Free crystalline silica: possibilities and limitations of its detection and
      determination in dust using infrared spectrometry].
AB  - The effect of the commonly occurring industrial dust components on the detection
      of crystalline silica and crystobalite by means of infrared spectrometry was
      investigated. The influence of minerals interfering in infrared with quartz and
      crystobalite: kaolinite, microcline, albite, mullite, and amorphous silica, as
      well as of the mixture of SiO2 crystalline forms was analyzed. The study was
      based on the computer-aided summing up of crystalline silica spectra with spectra
      of interfering components and spectra resulting from further transformation:
      deconvolved spectra, the second and fourth orders derivative spectra. It was
      found that the smallest amount of silica, possible to be detected in mixtures
      with interfering components amounted to 1-5% and crystobalite to 2-10%. The limit
      of detection, using the pellet technique in the adopted conditions of spectra
      registration, accounted for 0.5 microgram for silica and 1 microgram for
      crystobalite, whereas using PVC filters, 1 microgram of silica and 4 micrograms
      of crystobalite could be detected.

PMID- 11828848
TI  - [Alive microorganism in the workplace ambient air in plants disposing communal
      waste].
AB  - This paper presents the results of the identification and determination of alive
      microorganisms in the air samples collected from the breath zone of workers
      employed in the waste collection and disposal. Samples were taken during waste
      collection and in the waste reloading, sorting and composting plants. In
      addition, samples were taken at stationary sites: in the city and inside flats.
      Different kinds of species of Gram-positive bacteria (Micrococcus,
      Staphylococcus, Enterococcus, Bacillus, Listeria, Corynebacterium, Rhodococcus)
      and Gram-negative rods (Enterobacteriaceae, Pseudomonas and other aerobic
      bacteria) were found. On every work site, there were fecal bacteria (Escherichia
      coli, Enterococcus faecalis and Enterococcus faecium). The city areas and flats
      were free from this kind of bacteria. The number of mesophilic bacteria and
      thread-like fungi exceeding 10(4) cfu/m3 of air was counted on every work site.
      The largest number of mesophilic bacteria and Actinomycetes were found in the
      waste composting plant (10(4)-10(6) and 10(3)-10(5) cfu/m3, respectively),
      whereas the majority of fungal spores were counted during waste collection and
      sorting. (10(4)-10(5) cfu/m3). On the city streets there were no Actinomycetes
      and the number of fungal spores (10(4)/m3 of air) was similar to that observed in
      the waste reloading and composting plants. The amount of mesophilic bacteria in
      the city and flat samples was below 10(2)-10(3) cfu/m3. As to the number of
      fungal spores and Actinomycetes there was a limit of determination (10(1)-10(2)
      cfu/m3). The majority of mesopholic bacteria identified in the air were
      classified as the second group of occupational risk in the Council Directive
      54/2000/EU. Bearing in mind that Gram-negative rods (especially intestinal) were
      identified in all samples, it is suggested to use endotoxin concentration as one
      of possible criteria for assessing the hygiene conditions at workplaces.

PMID- 11828850
TI  - [High density lipoprotein cholesterol level in rats poisoned with cadmium].
AB  - The effect of cadmium on lipid metabolism in persons occupationally and
      environmentally exposed to this metal may lead to the occurrence of
      cardiovascular diseases. The disturbances of the reverse transport of cholesterol
      could be responsible for the vascular changes. The aim of this study was to
      evaluate the impact of cadmium on the cholesterol level in the main fraction and
      subfractions of high density lipoprotein (HDL). The cholesterol level was
      measured in serum of rats treated with cadmium in a weekly dose of 5 mg/kg b.w.
      for seven weeks and in controls. After a seven-week exposure, the decreased HDL2,
      and the increased HDL3 cholesterol levels were observed in cadmium-poisoned
      animals as compared to controls. The results of the study suggest that a cadmium
      impaired mechanism of the cholesterol transport in blood may induce vascular
      changes.

PMID- 11828849
TI  - [Sensitization to cow and pig allergens among farmers in Eastern Poland].
AB  - The study aimed at assessing the frequency of sensitization to cow and pig
      allergens among farmers in Eastern Poland. Sixty eight farmers from 17 randomly
      selected family farms were examined. The study group included 30 females and 38
      males, aged 18-84 years (median, 47 years), with exposure duration ranging from 1
      to 80 years (median, 30 years). The farmers were interviewed and subsequently
      skin prick-tested with cow and swine epithelia. Blood samples were examined for
      the presence of IgE antibodies, specific to cow dander and swine epithelium,
      using enzyme immunoassay (UniCAP). None of the farmers complained of any symptoms
      when working with cows or pigs. In 13 farmers (19.1%) either positive skin pick
      test and/or the presence of IgE specific to cow and/or pig were found. Seven
      farmers (10.3%) reacted to skin prick tests: 2 to cow epithelium; 2 to pig
      epithelium; and 3 to both allergens. Specific IgE was also found in 7 farmers
      (10.3%): in 4 to cow dander; in 1 to cow epithelium; and in 2 to both allergens.
      There was a very weak correlation between skin tests and IgE determination; only
      one farmer showed positive reaction to cow allergens in both skin tests and IgE.
      Following the results of the previous and the present studies, it was concluded
      that in Poland the farm animal allergens are less important causes of work
      related diseases than plant allergens.

PMID- 11828851
TI  - [Specific nature of the software used to construct simulations: physiologically
      based toxicokinetic models].
AB  - Building of the physiologically-based toxicokinetic (PBTK) models is based on the
      application of simulation languages, such as advanced continuous simulation
      language (ACSL). The aim of this study was to develop the principles of
      constructing the fundamental model and the models dedicated to chemicals found in
      the work environment (e.g. trimethylbenzene (TMB) isomers present in the
      petrochemical, paint and lacquer and related industries). The fundamental model
      is based on four main compartments (fat tissues, richly perfused tissue, slowly
      perfused tissue and liver) and six auxiliary compartments (lungs, venous blood,
      arterial blood, body weight, inhaled air and exhaled air). The basic element of
      the PBTK model comprises blocks containing definitions of variables and constants
      supplemented by the following parameters: command, calculated, transferred and
      resulted. The models dedicated to various chemicals and organisms are built by a
      suitable modification of the fundamental model. All sets of command parameters
      values for the organism, chemical and simulation are written in the text files
      and loaded before or during the simulation. The empirical data obtained in
      experiments with volunteers are used in a similar way. The specimen dedicated
      model was built for 1,2,3-TMB (hemimellitene). 2,3-Dimethylbenzoic acid (2,3,
      DMBA) (a hemimelitene metabolite) excretion rate data obtained from an experiment
      during which volunteers were exposed to hemimellitene at 25 at 100 mg/m3 were
      compared with the results of the computer simulation. A high convergence of the
      comparable values was obtained. Simulations were also made for exposure periods
      of one week and one month. The results confirmed the experiment-based
      recommendations on the assessment of the occupational exposure. The application
      of the new physiologically-based toxicokinetic models renders it possible to
      forecast toxic chemical (or it metabolite) concentrations corresponding to the
      concentrations of those chemicals in the workplace atmosphere.

PMID- 11828852
TI  - ["Sick building syndrome"--a new problem of occupational medicine].
AB  - "Sick building syndrome" (SBS) is a group of symptoms experienced by people
      working in various buildings. This term or another one "building-related illness"
      (BRI) is used to define illnesses related to non-industrial and non-residential
      buildings, mainly modern offices, in which people spend many working hours.
      Specific BRI applies to a group of illnesses with a fairy homogeneous clinical
      picture and known etiology (infectious, immunological or allergic). Non-specific
      BRI applies to a group of heterogeneous and non-specific, work-related symptoms,
      including irritation of skin and mucous membranes of the eyes, nose and throat,
      headache, fatigue and concentration difficulties. BRI seems to be related to
      inadequate ventilation, humidity and temperature changes, chemical and biological
      contaminants from indoor and outdoor sources. Sick building syndrome is
      considered as an important problem of occupational medicine, bearing in mind that
      50% of the entire workforce in industrialized countries work in this type of
      buildings, and nearly 20-30% of this group of workers report symptoms suggesting
      the prevalence of sick building syndrome.

PMID- 11828853
TI  - [Molecular aspects of toxic effects of nitric oxide].
AB  - Although Nitric oxide (NO) is involved in many physiological processes of the
      body, its physico-chemical properties may, under some conditions, become
      dangerous to living cells. NO exposure may be of endogenous (e.g. local
      overproduction by activated inflammatory cells) or exogenous origin (mainly by
      inhalation route). Together with a short review of potential sources of NO
      exposure, the author presents some molecular aspects of its toxic effects:
      prooxidant effect, genotoxicity and mutagenicity, impact on the cell cycle and
      feedback inhibitory effect on NO synthase.

PMID- 11828854
TI  - [Photosensitivity induced skin diseases].
AB  - The causes of skin diseases associated with photosensitivity are presented. The
      combined effect of light and exogenous light sensitizing substances leads to the
      occurrence of phototoxic and photoallergic reactions, and what is more, UVA
      spectrum is most active in their pathogenesis. The light sensitizing compounds
      are contained in cosmetic preparations, drugs and certain plants. They are
      characterized by a tricyclic structure and the ability to absorb ultraviolet
      radiation. The light sensitizing properties are exhibited primarily by non
      steroid anti-inflammatory drugs, preservatives, sun filters, phenothiazine
      derivatives and odorants. Photoallergic reactions may be of occupational nature.
      The majority of reports found in the literature concern farmers, gardeners, fruit
      growers and breeders, as well as representatives of other occupations. They
      usually emerge after the contact with pesticides of the thiocarbamide group,
      tetrachloroisophthalonitryl and veterinary drugs. The cases of occupational
      eczema in farmers and gardeners induced by the effect of light sensitizing plants
      have also been reported. In addition, the photoallergy diagnostic methods are
      discussed.

PMID- 11828855
TI  - [Comments about a new legislation regarding sick leave for teachers in Poland].

PMID- 11828856
TI  - Bless all the people of the world.

PMID- 11828857
TI  - Adolescents' input on the development of an HIV risk reduction intervention.
AB  - Adolescence is a developmental period often associated with sexual debut as well
      as risk taking. Given these considerations, HIV prevention interventions need to
      become an important component of adolescent health care. This article describes
      the use of formative research to guide intervention refinement. To refine an HIV
      risk reduction intervention that has been used successfully with adults, the
      authors conducted focus groups with 30 adolescent females. These participants
      identified misconceptions regarding HIV-related information and factors that
      influence motivation to participate in risky behaviors. They also suggested
      strategies for recruitment and retention in a longitudinal study. Formative
      research such as this can be used to develop interventions that are gender
      specific and developmentally and culturally appropriate for adolescents.

PMID- 11828858
TI  - The role of exercise in the prevention and treatment of wasting in acquired
      immune deficiency syndrome.
AB  - Involuntary weight loss with lean tissue depletion is a serious and AIDS-defining
      complication of HIV infection. This article explores definitions of AIDS wasting
      syndrome (AWS), its etiology, methods of assessing body composition, and
      pharmacological treatments. Recent research literature on the role of exercise in
      the prevention and treatment of AWS is reviewed. Included are studies of the
      safety of exercise, the effects of exercise on the immune system, and the effects
      of exercise on weight gain and body composition as well as studies of exercise in
      combination with medications and other interventions. Implications for clinical
      practice are discussed.

PMID- 11828860
TI  - Continuation of postpartum antiretroviral therapy in a cohort of women infected
      with human immunodeficiency virus.
AB  - A common dilemma for HIV-positive pregnant women is the issue of continuation or
      cessation of antiretroviral therapy (ART) postpartum. Current guidelines for ART
      during pregnancy offer no specific recommendations for postpartum ART care. The
      objective of this study was to ascertain characteristics that would predict
      cessation or continuation of ART postpartum. In this study, prenatal and medical
      clinic records were reviewed retrospectively for a cohort of 29 HIV-infected
      pregnant women who were seen in the Temple University High Risk obstetrics
      practice from 1997 to 1998. All women took ART during pregnancy, except for one
      who received i.v. AZT and nevirapine during labor. HIV-specific medical care was
      provided concurrently during the time of the woman's obstetrics visit by a nurse
      practitioner and a clinical nurse specialist in consultation with the physician.
      Factors that were included for review included race, age, use of ART at the time
      of pregnancy diagnosis, type of ART during pregnancy, CD4 count, HIV-1
      ribonucleic acid polymerase chain reaction (RNA PCR) levels, current substance
      use, disclosure of HIV status to current partner, years of HIV infection, prior
      HIV infected child, and whether this was a first pregnancy. The two groups of
      women were divided between those who discontinued ART postpartum and those who
      continued ART. The data were analyzed with the Kruskal-Wallis test for two
      groups, or calculations of risk ratios with Fisher's exact test. Study results
      indicated that 15 out of 29 women (51%) continued ART postpartum. The significant
      factors for continuation included Latina ethnicity (risk ratio = 0.24, confidence
      interval = 0.06-0.87), CD4 < 200 mm3 (p = .04), and a greater number of drugs in
      the antiretroviral regimen 3 versus 2 (p = .05). This study showed that
      postpartum continuation of ART was associated with identified Latina ethnicity,
      lower CD4 counts, and a greater number of drugs in the pregnancy regimen. Further
      study is recommended to understand the clinical impact of intermittent ART, the
      strategies for postpartum therapy adherence, and clinical follow-up.

PMID- 11828859
TI  - Treatment of anemia in patients with HIV Infection--Part 2: guidelines for
      management of anemia.
AB  - The key treatment goal for managing anemia in patients infected with HIV is to
      maintain an improved or normal hemoglobin level. Whenever possible, the
      identification and treatment of the underlying cause of anemia is the primary
      therapeutic strategy. After excluding other etiologies, the Nursing Guidelines
      Committee for Anemia in Patients With HIV Infection has recommended that patients
      with mild asymptomatic anemia (hemoglobin level = 1 g/dl below the lower limit of
      the normal range) receive nutritional support and more frequent screening.
      Recombinant human erythropoietin (epoetin alfa) therapy is an appropriate
      treatment option for patients with symptomatic mild anemia or moderate anemia
      (hemoglobin level = 2 g/dl below the lower limit of the normal range). An
      immediate blood transfusion may be required under specific instances for patients
      with severe anemia (hemoglobin level less than or equal to 8 g/dl).

PMID- 11828862
TI  - Antiretroviral therapy for HIV: drug resistance and sequencing.

PMID- 11828861
TI  - Psychometric properties of the HIV-Related Fatigue Scale.
AB  - The HIV-Related Fatigue Scale (HRFS) was developed to address the specific
      aspects of fatigue experienced by people who are HIV-positive and are not
      measured in any commonly used fatigue scale. The necessity for a new scale was
      determined after analysis of a qualitative study to explore HIV-related fatigue
      in which it was found that HIV-related fatigue has components related to
      intensity, circumstances, and consequences that must be included in the
      measurement of fatigue for this population. The HRFS has 56 items, most of which
      are on a 1-to-10 scale, drawn from five existing fatigue scales and the data from
      this qualitative study. The items were deemed content valid, easy to understand,
      and not fatiguing to complete by people with HIV-related fatigue. Cronbach's
      alpha for the entire tool was .94; internal consistency for each of the three
      preliminary subscales is reported as well. Test-retest reliability was moderate
      at r = .43. Further testing needs to be done, but the HRFS has the potential to
      be a valuable addition to the measurement of fatigue in seropositive persons.

PMID- 11828863
TI  - Primary care of anally receptive men.

PMID- 11828864
TI  - HHS seems to soften hard line on kickbacks.

PMID- 11828865
TI  - Debating RICO suits vs. health plans. States failed to protect docs from
      insurers.

PMID- 11828866
TI  - Debating RICO suits vs. health plans. Patients will suffer; greedy lawyers to
      blame.

PMID- 11828867
TI  - May I please see some identification?

PMID- 11828868
TI  - Compensation monitor. Primary care salaries 'go south'.

PMID- 11828869
TI  - Should Uncle Sam decide what works? Making the case for a 'health care Fed'.

PMID- 11828870
TI  - Health care should be more 'transparent'.

PMID- 11828871
TI  - Harness information to make health care work.

PMID- 11828872
TI  - Something 'nice' can come out of this.

PMID- 11828873
TI  - When physicians' skills fail, collaboration beats punishment.

PMID- 11828874
TI  - Quality concerns ensure consumers will gain clout. Interview by Patrick Mullen.

PMID- 11828875
TI  - A health care management company's experience with palivizumab.

PMID- 11828876
TI  - Terror's effect on technology adoption.

PMID- 11828877
TI  - Managed care outlook. Employers struggle to preserve pharmacy benefit.

PMID- 11828878
TI  - [The biology of aging].

PMID- 11828879
TI  - Relevance of in vitro studies for aging of the organism. A review.
AB  - Cell culture in vitro has been widely used to study aging at a cellular level.
      The criticisms that have been raised to the use of this experimental system are
      due to incorrect interpretations of the results obtained, and to ignorance of the
      physiological development of the human organism through its life span. The cell
      culture methodology has yielded fundamental knowledge concerning how a cell is
      modified through division, how this creates a change in cell function, and the
      consequences it has on cell interactions.

PMID- 11828880
TI  - Energetic stress in combination with tumor necrosis factor-alpha (TNF-alpha)
      induces apoptosis of human fibroblasts (WI-38) in vitro: reduced responsiveness
      of senescent cells.
AB  - The NaCl content of the culture medium of human fibroblasts (WI-38) was elevated
      from 0.12 M to 0.23 M. Previously it had been shown that exposure of fibroblasts
      to such high NaCl conditions resulted in a rise of both glycolysis and
      respiration ("energetic stress"), mainly due to increased demands of energy for
      active ion transport ("sodium pump"). While "young" (Phase II) and "senescent"
      (Phase III) cells did not show a significant increase of apoptosis over the basal
      rate (ca. 4%) under treatment with either a high-NaCl medium or TNF-alpha (10 nM)
      alone, combined treatment resulted in a strong increase in Phase II cells and a
      significantly lesser rise in the case of "senescent" Phase III cells. We
      conclude, therefore, that energetic stress stimulates sensitivity to apoptosis by
      (in the presence of) TNF-alpha, especially pronounced in potentially replicating
      "young" as compared with irreversible postmitotic ("senescent") fibroblasts.
      Possible causes of this differential responsiveness and implications for the in
      vivo situation (in the organism) were discussed.

PMID- 11828881
TI  - The role of apoptosis in aging and age-related disease: update.
AB  - Programmed death of cells by apoptosis is regarded as a protective mechanism of
      the organism against an accumulation and spread of defective cells. The rate of
      apoptosis is elevated in most types of aging cell populations. However, there are
      also findings about a decreased susceptibility of senescent cells in vivo and in
      vitro, particularly to apoptosis induced by oxidative and energetic stress.
      Mitochondria appear to have a key function in apoptosis regulation. Thus,
      apoptosis can be induced by defective mitochondrial oxidative phosphorylation.
      The role of apoptosis in aging and age-related disease was outlined for different
      organs (brain, cardio-vascular system, immune system, intestine, macula of the
      eye, Langerhans islets, prostate gland, oocytes of ovaries). The age-related
      intensification of this dismantling system of cells seems to highlight the
      deterioration of tissue and organ structure and function in aging.

PMID- 11828882
TI  - [The mitochondrial genome and aging].
AB  - There is a lot of evidence that age-associated alterations of the mitochondrial
      genome occur, especially in postmitotic tissues such as brain, heart and skeletal
      muscle. These alterations are supposed to be a result of an attack of free
      radicals generated as normal byproducts of oxidative phosphorylation and lead to
      damage of proteins, lipids, and DNA. The alterations of mtDNA include oxidative
      damage of base pairs, point mutations, large-scale deletions or duplications. The
      4977 bp deletion or "common deletion" reveals an age-dependent accumulation in
      postmitotic tissues, but not in fast-dividing tissues such as blood cells. In
      addition, it is observed that a tissue-specific accumulation occurs with the
      highest abundance in the basal ganglia, followed by skeletal muscle, heart, and
      lowest in cerebellar tissue. Third, pathological alterations of specific tissue,
      like ischemia/reperfusion events, display a pronounced accumulation of the
      deletion compared to age-matched controls. Because there are many mtDNA
      mutations, further analysis of all alterations of mtDNA will elucidate its role
      in the phenomenon of aging. Despite some criticisms of this free radical theory
      of aging, there is a lot of experimental evidence to support the important role
      of mitochondria in organismal aging.

PMID- 11828883
TI  - [Aging at the molecular level exemplified by proteins].
AB  - During their life span, human proteins may undergo post-translational
      modifications that can be interpreted as manifestations of protein aging. The
      most frequently discussed modifications in that context are oxidation, glycation,
      deamidation, isomerization and racemization. Their pathophysiological relevance
      depends on the availability of repair mechanisms and on the protein turnover.
      Proteins with high turnover will be exchanged before molecular modifications
      become relevant. The most affected proteins are long-living and permanent
      proteins. Such proteins can be identified by the determination of their D
      aspartic content (as a measure of an in vivo racemization and isomerization of
      aspartyl and asparaginyl residues). Using this method it could be demonstrated
      that numerous proteins in diverse human tissues are long-living or permanent and
      cannot escape post-translational modification by turnover. The human organism is
      confronted with an accumulation of "abnormal", post-translationally modified
      proteins during aging, especially in the extracellular space, but also at a
      cellular level. The exact pathophysiological dimension of post-translational
      modifications as manifestations of protein aging has to be further elucidated.
      However, they have been already discussed as relevant factors in the pathogenesis
      of diseases of old age.

PMID- 11828885
TI  - [Lipid peroxidation as a common pathomechanism in coronary heart disease and
      Alzheimer disease].
AB  - Oxidative processes are involved in aging as well as the pathogenesis of
      different degenerative diseases. In the last few years the role of low density
      lipoprotein oxidation in the development of artherosclerosis and coronary heart
      disease has become evident. Lipoprotein oxidation in plasma is used as a marker
      for disease progression. We were interested in the role of lipoprotein oxidation
      in Alzheimer's disease. For this purpose we developed methods to determine the in
      vitro oxidizability of cerebrospinal fluid and plasma lipoproteins of Alzheimer
      patients. In addition we measured the lipophilic and hydrophillic antioxidants,
      alpha-tocopherol (vitamin E) and ascorbate (vitamin C). Cerebrospinal fluid and
      plasma lipoprotein oxidation was found to be increased in Alzheimer's patients
      compared to controls and a corresponding decrease of antioxidant vitamins was
      found. In a pilot study, in vitro lipoprotein oxidation in cerebrospinal fluid of
      Alzheimer patients could be delayed by vitamin E and C supplementation. In
      conclusion these data show that increased lipoprotein oxidation could play an
      important role in Alzheimer's disease and possibly provide a rationale for the
      treatment of this disease with antioxidant drugs. The clinical effect of this
      therapeutical approach remains to be proved in long-term studies.

PMID- 11828884
TI  - Protein "AGEing"--cytotoxicity of a glycated protein increases with its degree of
      AGE-modification.
AB  - Non-enzymatic glycation of proteins with reducing sugars and subsequent
      transition metal-catalyzed oxidations leads to the formation of protein-bound
      "advanced glycation endproducts" (AGEs). They accumulate on long-lived proteins
      including on and in the vicinity of the beta-amyloid plaques in Alzheimer's
      disease (AD). Since the AGE modification of a protein increases with time, and
      such a "long-term incubation" might also occur in the AD brain, we investigated
      whether an increase in the cytotoxic effects of an AGE-modified model protein
      occurs over time. Bovine serum albumin (BSA) was modified by glucose for defined
      time periods, and the viability of SH-SY5Y neuroblastoma cells, incubated with
      the differentially AGE-modified BSA samples, was measured with the MTT assay.
      Cytotoxicity of the AGE-modified BSAs increased in correlation to the incubation
      time with glucose. Among the AGE-specific markers, browning (OD 400) correlated
      best with cytotoxicity, followed by AGE-specific fluorescence and the defined
      AGE, carboxymethyllysine. Since AGEs accumulate in AD over time, they may be one
      of the "age-related" factors contributing to neuronal cell death in Alzheimer's
      disease.

PMID- 11828886
TI  - [Possibilities of regression in arteriosclerosis].
AB  - We studied the hypercholesterolemic rabbit model in order to evaluate potentials
      of regression of arteriosclerosis by measuring various blood and plaque
      parameters. After induction of arteriosclerosis by feeding a 2% cholesterol
      enriched diet (CHF) for 6 weeks, the highly increased blood lipid levels
      decreased significantly under normal diet, while the cholesterol concentration,
      the lumen stenosis, and the number of smooth muscle cells in the plaques of the
      thoracic aorta still significantly increased. Sixty-eight weeks after reaching
      normal blood lipid levels, cellular density and number of macrophages
      significantly diminished; cholesterol concentration and lumen stenosis did not
      change significantly, whereas the smooth muscle cells further increased.
      Arteriosclerotic arteries of elderly people demonstrated a similar structure as
      seen after long-term regression in our experiments.

PMID- 11828887
TI  - [Changes in the collagen structures of human heart valves in relation to age and
      hypertension].
AB  - Using polarization microscopy and morphometrical methods, the influence of
      hypertension on the collagenous structures in the Lamina fibrosa of bicuspid
      valves of 14 middle-aged persons (30 to 50 years) were examined. The measurements
      were performed on histological sections. A group of 14 middle-aged subjects free
      from heart disease served as the control group. Furthermore, the results were
      compared to earlier findings on the histological biomorphosis of the
      atrioventricular valves. The following changes were observed and quantitatively
      determined: a) an enhancement of the percentage of the mechanically more
      resistant collagenous fibers (unsilvered, type I collagen), b) a stronger lateral
      aggregation of the collagenous fibrils of both types I and III collagen, c) a
      significant decrease of the total numbers of collagenous fibers per measuring
      area, and d) a significant decrease of the portion of silvered fibers (type III
      collagen) per measuring area for both sexes. The fiber density distributions
      confirm the observed changes: in the hypertension group the collagenous fibers
      are less densely distributed than in the control group. The observed regression
      of the content of collagenous fibers in the hypertension group is probably due to
      the anti-hypertensive treatment. Following the findings the turn-over of type III
      collagen is stronger influenced than that of type I collagen. The initial results
      determined in human heart valves confirm findings in animal models and
      characterize them with regard to the collagen types mentioned.

PMID- 11828888
TI  - [Soluble leukocyte adhesion molecules in vegetarians of various ages].
AB  - OBJECTIVES: Upregulation of leukocyte adhesion molecules under atherogenic
      conditions is accompanied by the release of soluble forms of adhesion molecules
      into the bloodstream. Vegetarians have a favorable cardiovascular risk profile.
      The aim of the present study was to assess the levels of circulating E-selectin
      (cE-selectin), circulating intercellular adhesion molecule-1 (cICAM-1), and
      circulating vascular adhesion molecule-1 (cVCAM-1) in both vegetarians and
      subjects of the average population and furthermore to evaluate the age dependence
      of cell adhesion molecules. METHODS: 24 male and 59 female vegetarians (mainly
      members of the German Society of Vegetarians) and 124 male and 179 female control
      subjects (volunteers, of the ILSE study Leipzig = Interdisciplinary Long Time
      Study of Health Adult Age and the Lipid-Study Leipzig), 18-89 years old were
      included in the study. The serum levels of circulating cell adhesion molecules
      were determined using monoclonal antibody-based ELISA assays (R & D Systems,
      Abingdon, Europe Ltd.). RESULTS: Vegetarians were characterized by a favorable
      lipid profile and a low prevalence of common risk factors for atherosclerosis.
      This group showed a tendency towards lower cICAM-1 levels in comparison with
      control subjects. Furthermore, significantly lower cE-selectin levels were found
      in the group of vegetarians. An age-dependent increase of cVCAM-1 and cICAM-1
      levels was found both in the group of vegetarians and control subjects. No
      significant differences were noted regarding the gender of the subjects included
      in the study. CONCLUSION: Low cE-selectin levels of vegetarians may reflect the
      favorable cardiovascular risk profile of this group. Furthermore, the present
      data indicate that cVCAM-1 and cICAM-1 are age-dependent parameters independent
      of risk for atherosclerosis.

PMID- 11828889
TI  - [The immune system in aging].
AB  - The immune system changes during life time. In this article we review which kinds
      of alterations take place. To exclude changes based on illnesses or chronical
      diseases, the SENIEUR protocol was performed, which defines "healthy elderly
      people". We focus on alterations in lymphocyte subsets, immunoglobulins and the
      cytokine network. Monocytes, eosinophils and basophils are without change during
      life, whereas the number of neutrophils and natural killer (NK) cells increase
      with aging. T- and B-lymphocytes are diminished in number as well as in function.
      The serum levels of immunoglobulins are mostly increased. The balance between TH1
      and TH2-cells is disturbed and also TH1- and TH2-specific cytokines. Theses
      changes and their effects on the health status of the elderly are discussed in
      detail.

PMID- 11828890
TI  - The case for supporting basic research in gerontology.
AB  - Basic research on aging has moved well beyond describing the aging of
      physiological systems and developing theories of aging, to the pursuit of
      mechanistic answers to questions such as: Why do we age? Why do individuals
      within a population age differently? Why do different species have such different
      life spans? How do aging changes increase the risk of developing age-related
      disease? and Can we develop safe and effective interventions to reduce age
      related disability? Two general areas of research promise to provide answers to
      these questions. One is the attempt to understand the mechanisms by which caloric
      restriction extends longevity and delays the onset of age-related disease. The
      other is the identification of genes which strongly influence the rate of aging
      in various animal model systems. Recent results in the latter area of research
      are providing new insights into the answers to these central aging questions and
      may help us understand how caloric restriction retards aging.

PMID- 11828891
TI  - Melatonin in elderly patients with insomnia. A systematic review.
AB  - BACKGROUND: Melatonin is a hormone and antioxidant produced by the pineal gland
      of which four neurobiological roles have been claimed in the aged population:
      anti-ageing agent; free-radical scavenger; regulator of circadian rhythm;
      endogeneous sleep-inducer. The "melatonin replacement" hypothesis states that 1)
      the well-evidenced age-related decline contributes to insomnia and that 2)
      replacement with physiological doses of melatonin improves sleep. The aim of this
      review was to determine the evidence for the efficacy of melatonin in elderly
      insomniacs. METHODS: MEDLINE's database from 1990-2000 was searched with
      "melatonin", "geriatrics" and "(frail)-elderly" as major sub-headings. This
      resulted in 78 articles: only studies with empirical treatment data were reviewed
      (N = 12). RESULTS: Six reports (abstract, research letter, retrospective case
      study, 3 open label studies) showed a trend towards efficacy of melatonin: sleep
      quality improved and in patients with Alzheimer's disease sundowning was reduced.
      In 6 double blind, randomised crossover trials, a total number of 95 patients
      (mean ages: 65-79 yrs) were treated. Melatonin doses ranged from 0.5 mg to 6 mg;
      most took a single dose 30-120 min before bedtime. In 3 studies a slow release
      form was used. Sleep quality was objectively measured by wrist actigraphy (n = 4)
      and polysomnography (n = 2), and additionally subjective sleep quality was
      assessed (n = 2). Sleep latency decreased significantly in 4 studies. In 3
      studies other measures of sleep quality (sleep efficiency, total sleep time and
      wake time during sleep) improved. Subjective sleep quality did not improve. No
      early-morning sleepiness occurred. Comparison of the studies suggests that
      melatonin is most effective in elderly insomniacs who chronically use
      benzodiazepines and/or with documented low melatonin levels during sleep.
      CONCLUSION: There is sufficient evidence that low doses of melatonin improve
      initial sleep quality in selected elderly insomniacs. However, larger randomized
      controlled trials, with less strict inclusion criteria are necessary to yield
      evidence of effectiveness (i.e. clinical and subjective relevance) in geriatric
      patients who suffer from insomnia, before wide-spread use can be advocated.

PMID- 11828892
TI  - [Psychiatric problems in the elderly--standardization of the Symptom Check List
      SCL-90-R in patients over 60 years of age].
AB  - In the following article, data of the symptom checklist SCL-90-R (Derogatis 1986)
      for elderly people are introduced, including an estimation of the controlling
      factors on psychological complaints in old age. The representative sample is
      based on 394 persons aged 61 to 96; their psychological complaints have been
      studied with respect to SCL-90-R. Evidently elderly people did not state an
      increasing load on psychological complaints, but a different structure of
      psychological symptoms. Therefore with increasing age the scales "Somatization",
      "Obsessive-compulsive" and "Phobic anxiety" increase, while "Interpersonal
      sensitivity", "Anger--hostility" and "Paranoid ideation" are decreasing. Within
      that frame, elderly females report increasing symptomatic load compared to
      elderly males. Furthermore, aspects of social support and health-related
      attitudes were found to be important predictors of psychological complaints in
      old age.

PMID- 11828893
TI  - [Severe decubitus ulcer: risk factors and nursing requirements in the terminal
      life phase].
AB  - We present an analysis of the risk factors, the origin and the nursing and
      medical practice of 140 deaths with high-grade pressure sores which had been
      detected by post-mortem examination before cremation. METHODS: All available
      nursing and medical records from nursing homes and hospitals were screened; in
      addition, relatives and head nurses were interviewed. The data sources were
      screened for individual risk factors, information about pressure sore prevention
      and treatment activities by nursing staff and general practitioners. Moreover,
      the utilization of pressure relieving devices for patients before and after
      development of the final decubitus was analyzed. RESULTS: More than 50% of the
      pressure ulcers had been incident in nursing homes. The mean duration of the
      disease was 307 days (median duration 123 days); the maximum duration ranged up
      to about 6 years. As far as it could be judged from the nursing records, there
      was a shortfall of nursing quality in terms of prevention efforts which appeared
      to be frequently inadequate in relation to the risk profile of the residents.
      Standardized pressure sore record files were missing in most of the cases.
      General practitioners were not involved in the treatment in 20% of all cases;
      some of them prescribed an obsolete wound management. In this study 52% of the
      patients had been classified into the maximum grade within the three-stage German
      nursing care insurance scheme. In cases of private care information about
      utilization of financial support and of professional help should be enforced.
      DISCUSSION: Being an indicator of nursing quality, shortfalls of prevention
      measures should be combatted by a broad pattern of quality management strategies
      which could be adapted from the clinical sector.

PMID- 11828894
TI  - Clinical evaluation of factors influencing toric soft contact lens fit.
AB  - PURPOSE: Some knowledge of the orientation position of toric soft lenses is
      required as part of the fitting process. Although it is known that factors such
      as lid anatomy, lens design, and fit are important, there is little detailed
      understanding of how these relate to toric lens orientation. The purpose of this
      study was to evaluate various patient and lens factors that might influence toric
      soft lens fit and to determine the predictor variables for lens orientation.
      METHODS: This was a clinical study in which 45 subjects were fitted with a prism
      stabilized, mid-water, cast-molded, back surface toric soft lens. The lens was
      representative of commonly used designs for frequent replacement toric soft
      lenses. Patient and lens fit variables were assessed, including a range of lid
      topography features, which were measured using a digital photographic technique.
      RESULTS: The main patient factors associated with lens orientation and stability
      were degree of myopia, palpebral aperture, and several angles relating to lid
      anatomy. Greater upward incline of the temporal lids was associated with
      increasing inferior-temporal lens orientation; lower myopia and smaller palpebral
      aperture size were associated with more stable lens orientation. The principal
      lens fit characteristics affecting lens orientation were postblink movement and
      lens tightness. Less movement was associated with more stable lens orientation,
      and increased tightness was associated with slower reorientation speed. Weaker
      but significant correlations were also shown between a number of other patient
      and lens variables. CONCLUSIONS: A number of patient factors and lens fit
      characteristics influencing toric soft lens orientation were identified. The
      findings fall short of allowing practitioners to accurately predict toric lens
      orientation; however, they do provide some factors to consider when fitting toric
      soft lenses.

PMID- 11828895
TI  - Corneal staining in hydrogel lens wearers.
AB  - PURPOSE: The purpose of this study was to determine the factors that contribute
      to corneal staining in hydrogel lens wearers by examining the following
      variables: type of lens worn, wearing time and lens replacement schedule, lens
      care system, and topical and systemic medication use. METHODS: Five hundred full
      time, successful hydrogel contact lens wearers were evaluated for corneal
      fluorescein staining at 20 clinical sites. Corneal staining was evaluated in five
      regions and was graded on a scale of 0 (no staining) to 4 (severe staining) in
      0.5 steps for severity. RESULTS: Corneal fluorescein staining was present in at
      least one eye in 55.7% of the hydrogel lens wearers examined in this study, and
      8.0% had moderate-to-severe staining (defined as a cumulative staining score of >
      or = 3 with at least one quadrant score > or = 2). Staining was most severe for
      the inferior portion of the cornea (mean +/- SD; OD: 0.34 +/- 0.57, OS: 0.30 +/-
      0.54). All other areas of the cornea showed lesser amounts of staining, all of
      which were approximately equal (mean range, 0.13 to 0.16). Staining was observed
      in two or more quadrants in 24% of right eyes and 22.4% of left eyes. When
      questioned about care system compliance, 81.1% of subjects reported compliance.
      Patients who were noncompliant with their lens care system (chi 2 p = 0.0037),
      used rewetting drops (chi 2 p = 0.0005), or wore conventional lenses without a
      planned replacement schedule (chi 2 p = 0.0008) were more likely to have some
      degree of corneal staining. Noncompliance with care system (chi 2 p = 0.0147),
      replacement schedule (chi 2 p = 0.0039), and lens power (chi 2 p = 0.0224) were
      associated with moderate-to-severe staining. The following factors were not
      significantly associated with corneal staining: patient age, gender, medication
      use including oral contraceptives, type of wear (extended, flexible, or daily),
      average wearing time, wearing time at the examination, lens type (spherical or
      toric), water content of lenses (high or low water content), type of care system,
      use of enzymes, and pinching the contact lens directly off the cornea.
      CONCLUSIONS: Staining occurs to some extent in many hydrogel contact lens
      patients, and is influenced by many factors. Moderate-to-severe staining, which
      may be more clinically significant, is associated with noncompliance with care
      system, a conventional replacement schedule, and lens power.

PMID- 11828896
TI  - A model of the prevalence and incidence of low vision and blindness among adults
      in the U.S.
AB  - Population-based vision screening studies of the prevalence rate of low vision
      and blindness in the U.S. are reviewed to evaluate the sources of disagreement
      among studies. The major reasons that studies disagree on prevalence rate
      estimates are differences in best-corrected visual acuity criteria for low vision
      and differences in the age range of the oldest age category. When corrections are
      made for these differences, the results of all prevalence rate studies, except
      the Mud Creek Valley Study, fit the same prevalence rate vs. age function. The
      greater prevalence rate of low vision and blindness for each age category that
      was observed in the Mud Creek Valley Study can be attributed to the higher
      prevalence rate of cataract associated with a paucity of health care services in
      the Mud Creek Valley population. The time-derivative of the prevalence rate vs.
      age function fit to the data provided an estimate of the annual incidence rate of
      low vision and blindness vs. age. The estimated annual incidence agreed with
      estimates from unpublished 8-year incidence data of the Baltimore Eye Survey. The
      incidence rate of low vision and blindness for Americans aged 40 to 60 years is
      higher among blacks than among whites. For Americans greater than age 60 years,
      the incidence rate for whites exceeds that for blacks. This observation probably
      reflects the different natural histories of glaucoma, a leading cause of low
      vision and blindness among black Americans, and age-related macular degeneration,
      a leading cause of low vision and blindness among white Americans. Using the age
      dependent models of prevalence rate of low vision and blindness for white and
      black populations, an estimated 1.5 million Americans over age 45 years have a
      best-corrected visual acuity in the better eye that is < or = 20/70. Based on the
      incidence rate estimates, approximately 240,000 new cases of low vision and
      blindness occur each year. With the aging of the U.S. population, that number is
      expected to double over the next 25 years.

PMID- 11828897
TI  - Testing night vision goggles in a dark outside environment.
AB  - BACKGROUND: People with degenerative retinal diseases such as retinitis
      pigmentosa, may have adequate day vision but suffer from poor night vision. We
      have tested newly developed night vision goggles (NVG) to help these patients
      overcome their night blindness, thereby promoting more opportunities for normal
      activities at night or in the dark. METHODS: A total of 42 subjects with night
      blindness due to retinitis pigmentosa, choroideremia, cone rod dystrophy, or
      Bardet Biedl syndrome were recruited and clinically examined (visual acuity,
      visual field, and contrast sensitivity). Using an experienced mobility trainer,
      we tested binocular NVG on the subjects in two locations: a dark room and a 1 to
      2 h outside course at night that provided different levels of difficulties (i.e.,
      obstacles, brightness, and contrast). The assessment of which patients benefited
      from the NVG was predominantly based on the subjective evaluation of the mobility
      trainer, followed by their graded responses on two questionnaires. RESULTS: Based
      on the evaluation of the mobility trainer, 23 (61%) of the 42 subjects
      experienced improved mobility and orientation with the NVG outdoors, and 19 (39%)
      subjects did not. The ophthalmic data demonstrated that a visual acuity better
      than 20/100 and a visual field > 5 degrees (Goldmann perimetry III4) is necessary
      to benefit from NVG usage. In addition, subjective responses on increased
      mobility and independence were positively correlated with successful NVG testing.
      CONCLUSIONS: Night vision goggles have the ability to improve poor night vision
      in subjects with visual acuity > 20/100 and a visual field > or = 5 degrees
      (Goldmann: III4). In so doing, NVG can help overcome the obstacles experienced by
      many people suffering from night blindness. NVG, therefore, have the potential to
      greatly improve quality of life.

PMID- 11828898
TI  - Seasonal variation in myopia progression and ocular elongation.
AB  - PURPOSE: To evaluate possible seasonal variations in myopia progression and
      ocular elongation in school children. METHODS: Seventy-one children who were
      enrolled in a clinical trial of bifocals were examined every 6 months for 30
      months. Three 6-month intervals ("winters") included none of the summer vacation
      from school, and two intervals ("summers") included all of the summer vacation.
      Myopia was evaluated, after cycloplegia with 2 drops of 1% tropicamide, by
      automated refractor, and changes in axial length and in vitreous chamber depth
      were measured by A-scan ultrasonography. Data from left and right eyes were
      averaged because there was no evidence of a significant eye-visit interaction.
      Analysis of variance with a planned contrast was used to evaluate differences
      between the observed rates of change over the two summers compared with expected
      rates assuming no seasonal effect. RESULTS: For 37 children in single-vision
      lenses, myopia progression rates over the two summers averaged 0.15 D compared
      with 0.32 D over the three winters. For 34 children in bifocal glasses, summer
      rates averaged 0.07 D compared with 0.30 D for winters. Analysis of variance
      showed that seasonal effects on myopia progression were significant (p < 0.025)
      for both groups for the first summer and approached significance for the second
      summer. Increases in vitreous chamber depth were also slower during the summer,
      significantly so (p < 0.01) for both summers in the single-vision group and for
      the second summer only in the bifocal group. Changes in axial length were
      somewhat slower in the summer, but the effect of season reached statistical
      significance in that variable only for the second summer in the bifocal group (p
      = 0.031). CONCLUSION: Myopia progression rates were slower during the 6-month
      periods that included all of the summer vacation than would be expected assuming
      no seasonal effect. Ocular growth was also slower in the summer; but that trend,
      in most cases, was statistically significant only for changes in vitreous chamber
      depth and not for axial length.

PMID- 11828899
TI  - Improving the effectiveness of the infant contrast sensitivity card procedure.
AB  - Based on results from an earlier prototype, custom software and printing
      techniques were developed to construct a new card-based test of contrast
      sensitivity (CS) for nonverbal subjects. Compared with the prototype, the new CS
      card test contains three improvements: (1) larger, more salient test gratings;
      (2) higher contrast warm-up cards for each spatial frequency set; and (3) smaller
      contrast step size between adjacent cards. The success of the new cards was
      evaluated by testing 3.5- and 12-month-old human infants. Results indicated that
      the new version of the test required little time to complete (mean, 6.5 min) and
      provided accurate estimates of visual acuity. Also, group contrast sensitivity
      functions (CSFs) showed substantial development from 3.5 to 12 months of age.
      Surprisingly, however, group CSFs obtained with the new cards were lower than
      those obtained with the prototype, a discrepancy that may be due to differences
      in space average luminance between the two sets of cards. In all, the new CS card
      procedure possesses several merits that give it potential as an option for
      assessing spatial vision in infants, toddlers, and subjects with multiple
      impairments.

PMID- 11828900
TI  - Correlation between optical and psychophysical parameters as a function of
      defocus.
AB  - PURPOSE: To evaluate how ocular optical image quality and psychophysical
      estimates of visual performance compare to each other as a function of defocus.
      METHODS: We measured the optical modulation transfer function using a double-pass
      apparatus and psychophysical estimates of visual performance: contrast
      sensitivity function (CSF) and visual acuity. Both sets of data were obtained
      under the same optical conditions. RESULTS: We measured optical and
      psychophysical parameters as a function of defocus. We studied the correlation
      between optical parameters (Strehl ratio and the logarithm of the volume in the
      double-pass image [log_Vol D-P]) and psychophysical parameters (the area under
      the fitted CSF represented in a logarithmic scale with the spatial frequency in
      linear scale [Area CSF-log_lin] and visual acuity) for different values of
      defocus. CONCLUSIONS: Strehl ratio is well correlated with the psychophysical
      estimates of the visual performance for moderate amount of defocus (within 1 D),
      whereas the other parameter (log_Vol D-P) is well correlated for larger ranges of
      defocus (within 2 D) and for different pupil diameters. These results suggest
      that optical measurements could be used for clinical testing of ophthalmic
      optics.

PMID- 11828901
TI  - Oblique central refraction in tilted spherocylindrical lenses.
AB  - Spectacle corrections worn in a frame with a faceform tilt should be used with
      effective spherocylindrical parameters. For the case of oblique central
      refraction, Keating presented a procedure to determine these parameters in a
      third-order approximation. The central equation of his approach, the effective
      dioptric power matrix, is partly the result of an educated guess. Based on the
      equations of wavefront tracing, an analytical derivation of his equation,
      slightly modified however, is given in this paper.

PMID- 11828902
TI  - Image quality and visual performance in the peripheral visual field following
      photorefractive keratectomy.
AB  - PURPOSE: A theoretical and experimental study was performed to assess the
      possible effects of photorefractive keratectomy (PRK) on retinal image quality
      and thresholds in the peripheral visual field. METHODS: Simple optical
      calculations suggest that although the quality of the retinal image at the fovea
      of the postoperative PRK eye may be comparable to that in an emmetropic eye,
      images in the peripheral field may be markedly worse, since peripheral ray
      bundles may pass partly through ablated and partly through unablated cornea,
      giving a simultaneous-vision bifocal effect. This would be expected to create an
      annular zone of confusion, so that light from two different directions in object
      space arrives at the same point on the retina. The position of this zone and its
      width are a function of the ablation zone geometry, the attempted correction, and
      the pupil diameter, but the major effects typically occur at field angles between
      about 40 degrees and 60 degrees. To explore this effect, Goldmann static
      quantitative perimetry was carried out along the 0 degree to 180 degrees meridian
      in six patients who had undergone myopic PRK and eight emmetropes. RESULTS: The
      results showed that thresholds for the PRK group at field angles from 40 degrees
      to 60 degrees were significantly higher than those of the emmetropic group (P <
      .01). These findings arise because the retinal images in the peripheral field of
      originally myopic, postoperative PRK patients are, in general, significantly
      degraded in comparison with those of emmetropes. CONCLUSION: Although under
      photopic conditions, retinal image quality close to the visual axis in patients
      who have been corrected by PRK is similar to that in emmetropes, it may be
      markedly worse in the peripheral visual field.

PMID- 11828903
TI  - Prospective randomized study of corneal aberrations 1 year after radial
      keratotomy or photorefractive keratectomy.
AB  - PURPOSE: To evaluate the optical properties of the cornea 1 year after either
      radial keratotomy (RK) or photorefractive keratectomy (PRK) in a randomized group
      of patients with low myopia. METHODS: Ninety-six patients with myopia between 
      0.75 and -5.00 D were randomized to either radial keratotomy (n = 46) or
      photorefractive keratectomy (n = 50). Topography maps were obtained 1 year after
      surgery and analyzed by computation of total corneal wavefront aberration and
      Zernike polynomial coefficients for pupil sizes of 2, 4, and 6 mm. The 4-mm pupil
      size was used for optimization of the model. RESULTS: The total corneal wavefront
      aberrations after RK and PRK were similar and not statistically different.
      Wavefront aberrations arising from astigmatism or defocus accounted for
      approximately 70% of the total wavefront error at all pupil sizes in both groups.
      All types of aberrations, and in particular spherical aberration, increased
      significantly with increasing pupil size. Higher-order wavefront aberrations were
      almost twice as high after RK than after PRK at pupil sizes of 4 and 6 mm.
      Spherical aberration and coma were slightly higher after PRK than after RK.
      CONCLUSIONS: Pupil size had a major effect on corneal aberrations after RK and
      PRK. The most important aberrations were sphero-cylindrical, in which eyes became
      significantly more myopic with increasing pupil size. The image forming
      properties of the cornea are better after PRK compared with RK due to the lesser
      amount of higher-order aberrations.

PMID- 11828904
TI  - Results of photorefractive keratectomy for hyperopia using the VISX star excimer
      laser system.
AB  - PURPOSE: To evaluate safety, efficacy, and predictability of photorefractive
      keratectomy (PRK) for hyperopic astigmatism of +1.75 to 00 D manifest refractive
      sphere and up to -2.50 D manifest refractive astigmatism using the VISX Star
      excimer laser system, version 2.5 software. METHODS: Treatment was performed on
      32 eyes of 21 patients. Eighteen of 21 patients were 45 years of age or older.
      Manifest and cycloplegic refraction together with Pelli-Robson contrast
      sensitivity assessment was performed prior to surgery and 1, 3, 6, 12, and 24
      months after treatment. RESULTS: Twenty-seven of 32 surgical procedures were
      reviewed 1 year after treatment (84%). Corneal epithelial healing was complete
      between day 4 and 10. Twelve months after treatment, 25 of 27 eyes (93%) achieved
      20/40 or better uncorrected visual acuity and 19 eyes (70%) achieved 20/20. No
      patient lost two or more lines of Snellen visual acuity assessed 6 months and
      later after treatment. The mean spherical equivalent refraction was reduced from
      +2.90 at baseline to +0.10 D at 1 year and +0.40 D at 2 years; 65% of eyes had a
      refraction within +/- 0.50 D. Four patients had further treatment by laser in
      situ keratomileusis for undercorrection in three eyes and overcorrection in one
      eye. Pelli-Robson contrast acuity was significantly reduced 12 months after
      treatment from a mean 1.72 before to 1.66 after PRK (P = .02, t-test).
      CONCLUSIONS: PRK for hyperopia using the VISX Star excimer laser system was
      effective in the treatment of hyperopic astigmatism. Although no patient lost two
      or more lines of high contrast best spectacle-corrected Snellen visual acuity 1
      year after treatment, there was a significant decrease in Pelli-Robson contrast
      acuity.

PMID- 11828905
TI  - Tracker-assisted versus manual ablation zone centration in laser in situ
      keratomileusis for myopia and astigmatism.
AB  - PURPOSE: Eye tracker systems have been developed concomitantly with small
      scanning beams to theoretically reduce ablation zone decentration and for
      accurate registration of all the laser pulses on the cornea. The purpose of the
      study was to compare the tracker-assisted with the manual centration method.
      METHODS: Twenty-five patients (48 eyes) with myopia and/or astigmatism had laser
      in situ keratomileusis (LASIK) between August 1998 and February 1999 with the
      Technolas 117C laser. Twenty patients (38 eyes, 80%) were available for follow-up
      at 3 months after surgery. Eyes were assigned randomly to one of two ablation
      zone centration methods: Group 1: Tracker-assisted (20 eyes), Group 2: Manual (18
      eyes). RESULTS: Mean distance between the ablation zone center and the pupillary
      center in the tracker-assisted centration group was 0.55 +/- 0.30 mm (range, 0.10
      to 1.4 mm), and in the manual centration group, 0.43 +/- 0.23 mm (range, 0.10 to
      1.0 mm) (P = .177). There was no statistically significant difference in
      postoperative contrast sensitivity, glare, and Topographical Corneal Surface
      Regularity Index (SRI) between the two groups. CONCLUSIONS: We obtained good
      results with both centration methods. We did not find superiority of the tracker
      assisted over manual regarding ablation zone centration, vision quality, or
      regularity of the ablation.

PMID- 11828906
TI  - Management of corneal ectasia after laser in situ keratomileusis with INTACS.
AB  - PURPOSE: To evaluate the safety and efficacy of intrastromal corneal ring
      segments (ICRS, INTACS, Keravision) for the correction of corneal ectasia after
      laser in situ keratomileusis (LASIK). METHODS: In this prospective,
      noncomparative case series, INTACS were implanted in three eyes (two patients)
      that were ectatic after LASIK. Mean follow-up was 8.7 months (range, 8 to 10 mo).
      RESULTS: No intraoperative complications occurred. After INTACS implantation,
      uncorrected visual acuity ranged from 20/20 to 20/25 at 6 months and remained
      stable until 9 months. Mean postoperative spherical equivalent refraction was
      0.50 D at 1 month and no significant changes appeared up to 9 months after INTACS
      implantation. After INTACS implantation, no eye lost any lines of Snellen
      spectacle-corrected visual acuity and two eyes gained from one to two lines.
      There was an increase in topographical regularity in all three eyes. CONCLUSION:
      Implantation of INTACS in eyes with corneal ectasia after LASIK resulted in good
      refractive outcome, absence of complications, and improvement in visual acuity.

PMID- 11828907
TI  - Risk factors for insufficient fixation of microkeratome during laser in situ
      keratomileusis.
AB  - PURPOSE: To investigate the potential risk factors leading to insufficient
      fixation of a microkeratome during laser in situ keratomileusis (LASIK),
      especially in Asian eyes. METHODS: We performed a retrospective analysis of 1809
      eyes of 972 patients that underwent LASIK. Profiles of patients (age, sex, past
      medical history, width of palpebral fissure, corneal power, and postoperative
      clinical course) whose operations were discontinued due to insufficient fixation
      were compared to all LASIK patients. RESULTS: Insufficient fixation was observed
      in 18 eyes of 16 patients. Those patients were significantly younger (26.1 +/-
      5.5 yr) compared to all patients (32.3 +/- 8.6 yr). Mean keratometric power was
      42.40 +/- 1.37 D in patients with insufficient fixation and 43.60 +/- 1.40 D in
      all patients (P < .001). Maximum width of palpebral fissure with eyes wide open
      was 0.96 +/- 0.20 mm in patients with insufficient fixation, and 1.10 +/- 0.19 mm
      in all patients (P = .0015). These patients subsequently underwent LASIK
      utilizing combinations of cooling, frequent corticosteroid instillation for
      several hours, and lateral canthotomy. CONCLUSION: Narrow palpebral fissures
      commonly found in Asian populations might be a risk factor for insufficient
      fixation of a microkeratome in LASIK, especially in young patients with flat
      corneas.

PMID- 11828908
TI  - Endotoxin levels in steam and reservoirs of table-top steam sterilizers.
AB  - PURPOSE: To document endotoxin levels in "Statim" cassette sterilizer reservoirs
      and in steam delivered to the cassette in the unwrapped instrument cycle. To
      document endotoxin levels in sterilizer reservoir water using different
      management protocols. METHODS: Endotoxin levels were determined using the Limulus
      Amebocyte Lysate test. Endotoxin preparations were from Escherichia coli and
      Ralstonia pickettii. All samples were collected in depyrogenated glassware and
      stored at -20 degrees C until assayed. RESULTS: The majority of water samples
      contained < 1.0 Endotoxin Unit (EU)/ml. The highest level found in sterilizers in
      clinical use was 5.3 EU/ml. Endotoxin was not detected in steam condensate within
      the limits of the assay. When the endotoxin level in the reservoir water was
      experimentally enhanced to 200 EU/ml, cassette steam condensate endotoxin levels
      were from 0.5% to 5% of the reservoir level. Daily and weekly emptying of the
      cassette reservoir consistently yielded low endotoxin levels as did monthly
      emptying, but with the latter there was a trend toward higher levels that favors
      weekly emptying as a precautionary measure. CONCLUSIONS: Endotoxin levels in the
      reservoirs of 23 sterilizers involving 240 samplings were never high enough to
      yield detectable endotoxin levels in steam in the sterilizer cassette. Regular
      weekly emptying of sterilizer reservoirs would eliminate the risk of endotoxin
      transfer during steam sterilization.

PMID- 11828909
TI  - Diurnal variation of human corneal curvature in young adults.
AB  - PURPOSE: To elucidate the diurnal variation of human corneal curvature with
      regard to gender and menstrual cycle. METHODS: Changes in corneal curvature and
      intraocular pressure (IOP) were measured over 24 hours in 14 young adults using
      corneal topography and a non-contact tonometer. In study 1, seven males and seven
      females (after menses) were measured. In study 2, four females out of the seven
      volunteers who participated in study 1 were measured again during menses.
      RESULTS: The females after menses showed a remarkable diurnal variation
      throughout 24 hours. A significant difference between the light-wake periods and
      dark-sleep periods of 0.83 +/- 0.15 D was found (P < .01). Corneal curvature was
      significantly flatter during menses than after menses in the light-wake period (P
      < .05). In the males, no significant diurnal change (0.21 +/- 0.12 D) was
      measured in corneal curvature. CONCLUSIONS: Diurnal variation of corneal
      curvature was significant, approximately 0.83 D in young females after menses,
      and corneal curvature became flatter during menses in young females. Diurnal
      variation of corneal curvature is an important parameter for planning refractive
      surgery and contact lens wear.

PMID- 11828910
TI  - Conoidal fitting of corneal topography height data after excimer laser
      penetrating keratoplasty.
AB  - PURPOSE: To demonstrate a mathematical method for approximation of discrete
      corneal topography height data with a biconic model surface for better
      appreciation of the optical performance of the graft after penetrating
      keratoplasty. METHODS: In this retrospective study we included 50 eyes of 50
      patients (30 keratoconus; 20 Fuchs' dystrophy) undergoing nonmechanical excimer
      laser penetrating keratoplasty. Conventional keratometry, corneal topography (TMS
      1), subjective refraction, and best spectacle-corrected visual acuity (BSCVA)
      were assessed preoperatively, 3 and 6 months postoperatively, and before/after
      suture removal. A biconic model surface was fitted to the topographic raw data
      (8.0-mm region of interest) minimizing the root mean square error and a set of
      parameters (meridional power, axis, conic constant, and approximation error) was
      determined. The refractive cylinder was correlated with keratometric power
      readings, the Simulated Keratometry (SimK) of the topography system, and the
      respective parameters of the model surface. RESULTS: Keratometric/SimK
      astigmatism increased from preoperatively (3.40/4.30 D) to 3 months (4.30/4.80 D)
      and decreased to 3.40/3.90 D after suture removal. Refractive cylinder/cylinder
      of the biconic increased slightly from 2.10/2.60 D preoperatively to 3.20/3.30 D
      after suture removal. The topographic cylinder SimK yielded the highest and the
      refractive cylinder the lowest values at each follow-up examination. Central
      keratometric power readings were stable before suture removal and decreased
      (about 1 D) due to suture removal. The conic constants in both meridional cross
      sections changed from a prolate to a spherical shape in the early time course
      after penetrating keratoplasty and reconverted to a prolate shape after suture
      removal. Regarding cylinder axis, there was a significant correlation of the
      model surface with the refractive cylinder at all examination (P < .05) but only
      a mild correlation of the keratometric and SimK cylinder axis to the refractive
      cylinder axis at some examination stages. CONCLUSION: Approximation of corneal
      topography height data with a biconic model surface renders reconstruction of
      clinically relevant corneal topography parameters including corneal asphericity
      with marked data compression. The correlation of amount/axis of refractive
      cylinder was best represented with the model surface parameters.

PMID- 11828911
TI  - Bivariate polar value analysis of surgically induced astigmatism.
AB  - PURPOSE: To demonstrate the use of bivariate polar value analysis of surgically
      induced astigmatism following various cataract incisions. METHODS: In a
      prospective study, we investigated surgically induced astigmatism following
      cataract surgery through 9.0-mm, 5.5-mm, and 4.0-mm superior corneal incisions.
      Autokeratometry was performed preoperatively and during the first year. All net
      astigmatisms were converted to polar values with reference to the 90 degrees
      meridian. Univariate and bivariate polar value analyses were performed. RESULTS:
      After 1 year, univariate polar value analysis disclosed flattening averaging 1.02
      D for 9.0-mm incisions, 0.71 D for 5.5-mm incisions, and 0.64 D for 4.0-mm
      incisions. The induced torque was 0.46 D counterclockwise for the 9-mm incision
      and close to zero for the 5.5 and 4-mm incisions. Bivariate polar value analysis
      disclosed a statistically significant (P < .05) difference in surgically induced
      astigmatism between the 9.0-mm incisions and the two smaller incisions at all
      follow-up points. CONCLUSION: Univariate polar value analysis demonstrated the
      surgically induced steepening and torque. Bivariate analysis demonstrated the
      joint variation in these entities and therefore always yielded the correct
      result. Univariate and bivariate polar values may be used for analysis of
      surgically induced astigmatism following cataract surgery in any meridian.

PMID- 11828912
TI  - Presumed reactivation of herpes zoster ophthalmicus following laser in situ
      keratomileusis.
AB  - PURPOSE: To report a case of herpes zoster ophthalmicus reactivation following
      laser in situ keratomileusis (LASIK) for myopia. METHODS: A 54-year-old healthy
      male underwent uneventful bilateral LASIK for the correction of myopia and
      astigmatism (-5.75 -3.00 x 20 degrees right eye, -5.50 -3.00 x 170 degrees left
      eye). Two months following LASIK, an epithelial dendritic lesion appeared in the
      lower third of the corneal flap of the left eye with vesiculoulcerative lesions
      of the lateral side of the tip of the nose. RESULTS: The patient was treated with
      topical and oral antiviral agents and had complete recovery of the lesions in 10
      days. CONCLUSIONS: Herpes zoster reactivation may occur following LASIK.
      Reactivation of herpes zoster in this case could have been coincidental, or
      secondary to LASIK and the subsequent use of topical corticosteroids following
      LASIK.

PMID- 11828913
TI  - Non-tuberculous mycobacterial keratitis at the interface after laser in situ
      keratomileusis.
AB  - PURPOSE: To describe two cases of bacterial keratitis with atypical mycobacteria
      after laser in situ keratomileusis (LASIK). METHODS: Two cases of non-tuberculous
      mycobacterial keratitis occurred in the interface between the stromal bed and
      flap, 20 days and 14 days after LASIK. The keratitis progressed slowly and
      worsened after attempts were made to remove the colonies. Mycobacterium fortuitum
      was confirmed 2 months after initial presentation following culture of the
      excised flap tissue in one case, and Mycobacterium chelonae was identified by
      culture of removed material and by RT-PCR with primers in the other case. The
      patients were treated medically and by surgical flap removal. RESULTS: In the
      first case, the keratitis was controlled only after removal of the partially
      melted flap and intensive medical treatment. In the second case, the lesion
      cleared after 2 months of antibiotics, but after tapering of antibiotics, the
      infiltrate progressed. Eventually, the keratitis was controlled after removal of
      the flap. CONCLUSIONS: Non-tuberculous Mycobacterium should be considered as one
      of the causes of keratitis when presenting as white colonies in the lamellar bed
      after LASIK. Treatment for 2 months may not be enough to eradicate the infection
      and excision of the flap may be necessary.

PMID- 11828914
TI  - Pellucid marginal corneal degeneration.

PMID- 11828915
TI  - Change in IOP in myopic eyes after excimer laser refractive surgery.

PMID- 11828916
TI  - Change in IOP in myopic eyes after excimer laser refractive surgery.

PMID- 11828917
TI  - Mesopic contrast sensitivity function after excimer laser photorefractive
      keratectomy.
AB  - PURPOSE: To evaluate contrast sensitivity under mesopic conditions in patients
      who had undergone uncomplicated excimer laser photorefractive keratectomy (PRK)
      for myopia. METHODS: Monocular contrast sensitivity function was measured with
      the Stereo Optical F.A.C.T. chart in 26 patients who had received PRK using the
      Nidek EC-5000 excimer laser system. Mean preoperative refractive error was -6.23
      +/- 1.69 D (range, -4.00 to -8.25 D); postoperatively, mean refractive error was 
      0.36 +/- 0.58 D (range, -0.75 to +0.50 D). Contrast sensitivity function was
      measured 6 months after surgery using four different chart luminances: 85, 5.0,
      2.5, and 0.1 cd/m2, the first being a photopic level and the rest mesopic. A
      control group of eight emmetropic subjects was also studied to allow comparison
      of results for statistical purposes. RESULTS: Logarithmic values of contrast
      sensitivity at each spatial frequency were used for statistical analysis and
      normalized values were used for graphical representation. The results showed a
      statistically significant reduction (P < .01) in contrast sensitivity for the PRK
      patients in comparison with the control group under mesopic conditions for each
      spatial frequency tested (1.5, 3, 6, 12, and 18 c/deg), although no significant
      contrast sensitivity differences were observed between PRK and control groups at
      the photopic (85 cd/m2) level (P > .01 for all frequencies). CONCLUSION:
      Photorefractive keratectomy can induce significant reductions in contrast
      sensitivity under mesopic conditions, even though the photopic contrast
      sensitivity function is normal.

PMID- 11828918
TI  - [Cardiologists in France. A programmed demographic decline].

PMID- 11828919
TI  - [Registry of cardiac insufficiency in cardiology].
AB  - The epidemiological data on cardiac insufficiency in cardiology are very scarce.
      Therefore, with its members the National College of French Cardiologists has
      conducted a survey in order to evaluate the clinical, biological and therapeutic
      characteristics of cardiac insufficiency patients, and thus the possible seasonal
      variations, and to compare them to the current recommendations and to the data
      from a previous survey with the same methodology performed in 1994. During each
      season of the year 622 cardiologists recruited the first 5 cardiac insufficiency
      patients who had been stable for at least three months. 8618 observations were
      analysed. The results showed 68% are male with an average age of 70 years, with
      an ischaemic aetiology in 47% of cases, hypertensive in 23%, and in NYHA stage II
      or III in 94% of cases. The left ventricular ejection fractions are < 30% in 22%
      of cases, between 30 and 50% in 62% of cases, and > or = 50% in 16% of cases (20%
      in those over 78 years). Medical treatment includes diuretics in 78% of cases,
      with 28% of patients on spironolactone, angiotensin converting enzyme inhibitors
      (ACE inhibitors) in 82% of cases, betablockers in 29% of cases; ACE inhibitors
      and betablockers are clearly prescribed more often than during the previous 1994
      survey but at doses often lower than the recommendations. Lastly, there are no
      seasonal variations in prescriptions.

PMID- 11828920
TI  - [Characteristics and predictive value of quality of life in a French cohort of
      angina patients].
AB  - The study of quality of life (QoL) in a French cohort of patients suffering from
      angina pectoris was one of the objectives of the ELAN longitudinal study. It
      concerned 3,954 subjects (76% males) mean age: 67 +/- 11 years, followed up by
      613 cardiologists which were invited to complete a series of baseline
      sociodemographic and clinical data and to answer a series of questions upon one
      year outcome (3,261 medical records available). QoL was assessed at baseline via
      a self-administered 12-item general questionnaire, the Short-Form 12 (SF-12),
      enabling to compute a mental component summary (CS-12) and a physical component
      summary (PCS-12) score. Mean MCS-12 in the ELAN cohort (49 +/- 7.5) was very
      close to the standards derived from general American population (50 +/- 10) or to
      the data available in a general French population (51.2 +/- 7.4). Whereas mean
      PCS-12 was hardly lower (about one standard deviation) in comparison with general
      American population (50 +/- 10) or with a general French population (48.4 +/-
      9.4). QoL was higher in males and linked to age in a contrasted way (higher MCS
      12 and lower PCS-12 in elderly; p < 0.0001). It depended on the clinical
      condition (lower MCS-12 associated with mixed-type angina pectoris or with more
      severe angina and with persistent smoking; lower PCS-12 associated with mixed
      type or more severe angina, with cardiac failure episodes, arteritis obliterans,
      stroke antecedents or left ventricular hypertrophy). Both scores were negatively
      correlated, in multivariate regression analysis, with the severity of persisting
      angina at one year, after controlling for the severity of baseline angina and the
      other confounding variables. Above all, MCS-12 and especially PCS-12, predicted
      major coronary events at one year (death, myocardial infarction, angioplasty,
      coronary by-pass surgery). In a multivariate logistic regression analysis, low
      baseline PCS-12 was associated with higher risk for cardiovascular death at one
      year (OR = 2.44; 95% CI = 1.25-4.74; p < 0.01). These results confirm the
      clinical validity of SF-12 (cross sectional stage of the study) and stress its
      prognostic value independent from the other risk factors (longitudinal stage of
      the study).

PMID- 11828922
TI  - [Long-term results of surgery for type A acute aortic dissection].
AB  - The cases of 160 patients (126 men, mean age 57.5 +/- 13.3 years) operated
      consecutively as an emergency for a Stanford type A dissection of the aorta
      between 1980 and 2000 were reviewed. The cumulative follow-up was 716.7 patient
      years with an average follow-up of 4.51 +/- 5.6 patient-years. The risk factors
      for early postoperative mortality (up to 3 months), late mortality (> 3 months)
      and reoperation (cardiac and/or vascular) were determined by multivariate
      analysis. The hospital mortality was 27.5%. Older ages, obesity, previous cardiac
      surgery, preoperative shock, medullary, renal or mesenteric ischaemia were
      significant risk factors for early mortality. The probability of actuarial
      survival was 66.1 +/- 3.8%, 57.7 +/- 4.2%, 52.2 +/- 4.6% and 45.3 +/- 5.5%
      respectively at 1, 5, 10 and 15 years. Chronic obstructive airways disease and a
      more recent operation date were significant risk factors for late mortality.
      Thirty patients underwent 37 reoperations after an average of 5.7 +/- 4.5 years.
      The actuarial probability for no reoperation was 96.9 +/- 1.8%, 74.7 +/- 5.3%,
      60.8 +/- 6.8% and 39.3 +/- 9.1% at 1, 5, 10 and 15 years respectively. The
      presence of severe preoperative aortic regurgitation was the only significant
      risk factor for reoperation. Type A acute dissection of the aorta continues to
      have a high early mortality and a significant incidence of late complications.
      Patients with severe aortic regurgitation before surgery are at high risk for
      reoperation and should probably have more radical aortic repair at the initial
      operation.

PMID- 11828921
TI  - [Programmed left ventricular stimulation in non-sustained ventricular
      arrhythmias].
AB  - The presence of nonsustained ventricular arrhythmia (NSVA) is an independent
      factor of sudden rhythmic death. The primary objective of our study was to
      evaluate the correlation between inducibility during programmed ventricular
      stimulation (PVS) and the presence of ventricular late potentials, the ejection
      fraction, the grade of arrhythmia, and the underlying cardiopathy. The secondary
      objective was to evaluate the interest of PVS in patients with NSVA. Ninety eight
      patients with NSVA have been tested by PVS and 14 were inducible. During the mean
      follow up of 24 months, 8 patients died, 3 of them suddenly. A significative
      statistical correlation was found between ventricular late potentials and
      inducibility (negative predictive value = 91%; p = 0.03). No correlation was
      found between the ejection fraction, the grade of arrhythmia, the cardiopathy and
      inducibility. In patients with ischaemic cardiopathy, PVS has allowed to identify
      a subgroup of patients with high risk of sudden death. In this subgroup, serial
      PVS for drug testing has contributed to choose the therapeutic regimen supposed
      to be more effective for prevention of fatal arrhythmia. Multiple factors explain
      sudden death, even though the initial treatment has been chosen by
      electrophysiologic studies. For non inducible patients, empiric treatment is not
      proven to be reliable, and the best therapeutic regimen is still unidentified,
      especially in the subgroup of patients with low ejection fraction. In this
      subgroup, the implantable cardioverter defibrillator vives better protection
      against sudden rhythmic death.

PMID- 11828923
TI  - [Cardiovascular risk in schoolchildren in rural Sousse, Tunisia].
AB  - There is no data available on the cardiovascular risk of children under 18 years
      of age in Tunisia, although it is well known that these risk factors present
      themselves in childhood. The authors performed an epidemiological study based on
      a representative sample of 793 schoolchildren in the rural region of Sousse, in
      Tunisia, to determine the incidence of the following risk factors: hypertension,
      hypercholesterolaemia and other lipid disorders, obesity and smoking. The main
      results show that the prevalence of hypertension is 11.2% with no statistically
      significant difference between the sexes. The prevalence of hypercholesterolaemia
      (2.9%), of hyper-LDL cholesterolaemia (0.6%) and hypertriglyceridaemia (1%) were
      comparable in boys and girls. Obesity (BMI > 30) was observed in 1.8% of the
      study population and was as common in girls (1.7%) as in boys (1.9%). Smoking was
      recorded in 4% of the study population and was commoner in boys (7.3%) than in
      girls (1.2%). This cardiovascular risk profile is encouraging and efforts should
      be made to maintain these levels until adulthood. This data will form the basis
      of a regional programme for the promotion of cardiovascular health in schools.

PMID- 11828924
TI  - [Severe intoxication with cardiotoxic drugs: value of emergency percutaneous
      cardiocirculatory assistance].
AB  - Acute severe self-administration of an overdose of betablockers, calcium
      antagonists or antiarrhythmic drugs is rare but carries a mortality of 10-15%.
      Between May 1997 and March 2000, 6 patients with an average age of 34 years
      (range 17-55 years) had a cardiac arrest on admission requiring emergency cardiac
      massage and emergency intubation with ventilatory assistance following massive
      ingestion of cardiotoxic drugs. Echocardiography confirmed complete biventricular
      akinesia. The surgical team implanted a cardiovascular assist device (ECMO: Extra
      Corporeal Membrane Oxygenation) by the femoral approach with pre-heparinated
      percutaneous cannula. The first two patients died of multi-organ failure due to a
      delay in the installation of the assistance. The 4 other patients survived
      without sequellae or recurrences. The average time on ECMO was 59.25 +/- 2 hours
      (range 48-71 hours). The early recognition of the indication for ECMO was one of
      the most important predictive factors for morbidity and mortality. The strategy
      of patient management should be determined in the emergency room: in cases of
      cardiocirculatory arrest resistant to symptomatic treatment (stomach washout,
      intravenous fluids, isoprenaline, inotropic agents) an echocardiogram should be
      obtained and the cardiac surgical team alerted to the problem. The introduction
      of pre-heparinated circuits, percutaneous cannula and peripheral shunts has
      widened the indications, efficacy (detoxification, restoration of peripheral
      tissue perfusion) and accessibility to this material, while limiting its
      duration. The collaboration of experienced multidisciplinary teams (emergency
      room staff, cardiologists, anaesthetists and surgeons) should optimise the timing
      of implantation and the monitoring of these systems and improve the results of
      resuscitation of these patients.

PMID- 11828925
TI  - [Epidemiology and prognosis of cardiac insufficiency].
AB  - Cardiac insufficiency, the outcome in the majority of cardiac diseases, is common
      and serious. The frequency is rising, and the fatality, even if it has diminished
      thanks to various treatments, remains elevated. The epidemiology of cardiac
      insufficiency is relatively little known in France, despite its considerable
      economic impact on the health system, while this constraint is ever increasing.
      Some significant French statistics: the number of cardiac insufficiency cases is
      about 500,000, there are 120,000 new cases each year. The incidence rises from
      4@1000 of males and 3@1000 of females aged between 55 and 64 years to 50@1000 of
      males and 85@1000 of females aged 85 to 94 years. The average age for occurrence
      of cardiac insufficiency is 73.5 years; two thirds of patients are over 70 years.
      There are about 3.5 million consultations and 150,000 hospitalizations for
      cardiac insufficiency every year. The average length of stay is 11 days. There
      are more than 32,000 deaths annually from cardiac insufficiency. The costs linked
      to cardiac insufficiency represent more than 1% of total medical costs. Cardiac
      insufficiency is a major problem for public health, and it is more and more so.
      This must prompt us to treat our patients better, and to undertake more
      preventive measures.

PMID- 11828926
TI  - [Secondary displacement of an Amplatz occluder for atrial septal defect. 2 case
      reports].
AB  - The authors report two cases of secondary displacement of an Amplatz occluder of
      isolated ostium secundum atrial septal defects. The displacement was observed at
      1 month and the prosthesis removed at 3 months. To the best of the authors'
      knowledge, these are the first two reported cases of secondary displacement of
      this type of device. The main risk factor in the two cases was the absence of a
      subaortic septal remnant observed at surgical removal. This anatomical
      characteristic can be identified by transoesophageal echocardiography, but was
      poorly assessed by transthoracic echocardiography. Three-dimensional
      transoesophageal echocardiography should improve selection of atrial septal
      defects suitable for percutaneous treatment by better identification of their
      form and anatomical characteristics.

PMID- 11828927
TI  - [Rupture of a sinus of Valsalva aneurysm in the left atrium].
AB  - Ruptures of sinus of Valsalva aneurysms are a rare complication, and very few
      cases of rupture in the left atrium have been described. In this clinical case we
      report the case of a patient hospitalised with a scenario of cardiac
      insufficiency revealing a very large posterior sinus of Valsalva aneurysm,
      associated with a bicuspid aortic valve, and rupture in the left atrium. The
      diagnosis was by transthoracic and transoesophageal multiplan echocardiography,
      and the treatment surgical, with a good result.

PMID- 11828928
TI  - [Can one die of sorrow?].
AB  - The authors report the case of a 49 year old woman who, on two occasions four
      years apart, presented with cardiogenic shock following the same type of intense
      emotional stress. Acute left ventricular systolic dysfunction in the initial
      phase regressed completely with drugs. A diagnostic investigation excluded
      atheromatous coronary artery disease, myocarditis and pheochromocytoma. Two
      hypotheses remained: prolonged coronary spasm causing myocardial stunning or
      acute catecholaminergic cardiomyopathy secondary to the stress.

PMID- 11828929
TI  - [Lyme disease presenting as infarction pain. A case report].
AB  - Lyme's disease is a multi-system condition due to infection with a spirochete
      (Borrelia Burgdorferi), transmitted by a tick. Cardiac involvement, which is not
      systematic, usually presents with transient atrioventricular block of varying
      degree. The authors describe an unusual presentation of the cardiac involvement
      of Lyme's disease with chest pain resembling an acute coronary syndrome in a 32
      year old man. The characteristic skin lesion (erythema migrans), the positivity
      of IgM serology, the myocardial scintigraphic results and the negativity of the
      work-up of other causes of this pain led to a diagnosis of myocarditis, the
      outcome of which was favourable with treatment by amoxycillin (3 g/day, orally).

PMID- 11828930
TI  - [Cardiac metastasis from a Merkel cell skin carcinoma. A case report].
AB  - The authors report the case of a cardiac metastasis of a Market cell skin tumour
      in a 72 year old woman, presenting with chest pain and infero-lateral myocardial
      ischaemia simulating an acute coronary syndrome. The diagnosis, suspected on
      echocardiography, was confirmed by thoracic CT scan. Markel cell carcinoma is a
      rare skin tumour classified among the malignant neuroendocrine tumours. It has a
      high metastatic potential, especially to the gastrointestinal tract and the lung.
      On the other hand, cardiac metastases are quite exceptionally rare.

PMID- 11828931
TI  - [Drugs affecting apoptosis in the immune system].
AB  - Apoptosis is a key feature in the physiological and pathological regulation of
      the immune system. Concerning its central immunoregulatory roles, it would be
      reasonable to attempt to influence the progression of autoimmune diseases by
      pharmacological intervention in the processes of apoptosis. Numerous compounds
      capable of influencing apoptosis are known, but their exact mechanisms of action
      are only in part understood. The majority of the known chemicals does not affect
      apoptosis selectively, but alters the function of the whole organism, therefore
      considerable side-effects related to the application of these compounds may
      appear. The complexity of this situation is indicated by findings that the same
      compound can either induce or inhibit apoptosis depending on the experimental
      system and concentration studied. Our knowledge will, presumably, be extended in
      the future that could lead to the safer clinical application of these compounds.
      In this brief review article we attempt to present a synopsis of the most
      important agents influencing apoptosis in the immune system from a clinical point
      of view.

PMID- 11828932
TI  - [Biventicular pacing in patients with severe heart failure].
AB  - According to initial clinical results biventricular pacing seems to be effective
      in the treatment of patients suffering from drug refractory severe heart failure
      combined with intraventricular conduction disturbance. Biventricular cardioverter
      defibrillators and biventricular pacemakers were implanted in patients suffering
      from drug refractory severe heart failure in 3 and in 2 cases, respectively
      (follow up > 6 months). NYHA III-IV functional class, low left ventricular
      ejection fraction (23.2 +/- 5.4%), wide QRS (> 150 ms) with left bundle branch
      block and lateral dyssynchrony were present in each case. The left ventricle was
      enlarged in each patient (end-diastolic/end-systolic diameter: 78.6 +/- 9.2/66.2
      +/- 8.1 mm). The indications of cardioverter defibrillator implantations were
      both sustained ventricular tachycardia and ventricular fibrillation, nonsustained
      ventricular tachycardia combined with syncope in 2 and in 1 case, respectively.
      The duration of QRS decreased (190 +/- 36 vs. 134 +/- 17 ms, p = 0.012) and wall
      movement disorder disappeared. At the last follow up every patients were in NYHA
      II functional class and a decrease in left ventricular diameter could be observed
      (end-diastolic: 72 +/- 10.4 mm, p = 0.07; end-systolic: 62 +/- 10 mm, p = 0.09).
      During the follow up period (7.3 +/- 1.7 months) 18 episodes of ventricular
      arrhythmias could be detected in the same patient. Biventricular pacemakers and
      cardioverter defibrillators were implanted and applied successfully in the
      treatment of congestive heart failure for the first time in Hungary. The effect
      of biventricular pacing on morbidity and mortality, the cost-effectiveness, the
      exact indication and the combined use with cardioverter defibrillator have yet to
      be proven in future randomized trials.

PMID- 11828933
TI  - [Contact dermatitis after topical use of ketoprofen gel].
AB  - Authors present 5 cases of generalized contact and photocontact dermatitis due to
      topically applied ketoprofen, a non-steroidal anti-inflammatory drug. They
      investigated the sensitisation and photosensitisation to the drug and also the
      possible cross-reactivity.

PMID- 11828934
TI  - [The role of knowledge about breast-feeding and infant nutrition in selecting the
      method of feeding].
AB  - Attitudes and believes towards primipara breast-feeding in the 2nd and 3rd
      trimesters were examined with a questionnaire survey in 91 cases. The
      questionnaire included 60 true and false statements about breast-feeding which
      were placed on a 5-grade Likert scale by the respondents based on to what extent
      they agreed with the particular statement. Significant differences could be
      detected in the evaluation of statements between women who stopped breast-feeding
      before the 6th month and those who did not, according to the appraisal of the
      next items: 1. If a baby is breast-fed too long it will find it difficult later
      to detach from its mother and will be less independent. 2. The same kind of
      relationship can be created with the baby during feeding it from a feeding bottle
      as during breast-feeding. 3. The baby has to be prevented from falling asleep
      during breast-feeding and has to be made active again with gentle pinches. 4. If
      the baby falls asleep during breast-feeding, it will suckle poorly. 5. The baby
      can be easily made give up crying at night, if it does not get used to being
      taken into its mother's arms. 6. The father is excluded from the intimate
      relationship formed during breast-feeding. The correction of these false beliefs
      can extend the time of breast-feeding.

PMID- 11828936
TI  - [Pal Gyorgy (1893-1976)].

PMID- 11828935
TI  - [Traumatic dissection of the aorta (external and iatrogenic traumas)].
AB  - The authors are looking over the notion of traumatic aortic dissection and
      introducing to its forms accepted today. The definition of the disease changed
      within the advance of medicine, it has been on the one hand tightened and
      increased on the other. In the era of the non-invasive medicine, with the
      external mechanical injuries also the physical and mental strains has been
      regarded as causes of the aortic dissection. By the widening spread of the
      invasive medicine a new category of aortic dissection has been appeared namely
      the iatrogenic trauma. Nowadays, those aortic dissections may be regarded as
      traumatic ones, which have been connected with external mechanical (indirect) or
      internal iatrogenic (direct) injuries. According to recent data, the incidence of
      traumatic aortic dissection is growing. The reasons for this are the expanding
      motorization, arteriosclerosis and the increasing age of life.

PMID- 11828937
TI  - [Mihaly Pekar, founder of a university medical library].

PMID- 11828938
TI  - [Molecular genetics and gene therapy in diseases of the esophagus, stomach, colon
      and pancreas].
AB  - There has been a major improvement in our knowledge in the area of molecular
      genetics in the past 20 years. It has become evident that genetic factors are
      important in the initiation, progression and prognosis of most diseases. Many
      studies addressed the issue of tumorigenesis, which provided insight into the
      molecular basis of the sequencional development of cancer, driven by the
      accumulation of genomic defects. Most of the neoplasms are genetically
      heterogeneous, independent pathways and simultaneous tumorigenesis may exist
      within the same organ. As some mutations exist in benignant and also in malignant
      conditions, it is an important challenge to define the molecular characteristics
      of significant versus non-significant lesions. A new form of therapeutic
      intervention is gene therapy. During the next decade it will likely play an
      increasing role in clinical practice and particularly in the treatment of cancer.

PMID- 11828939
TI  - [Decreased bone mineral density as a risk factor in the development of spinal
      deformities in neurofibromatosis].
AB  - Neurofibromatosis-1 is a here-do-familiar disorder that is associated with a
      variety of skeletal anomalies, mostly with spinal deformities in 10-50% of the
      patients. Intraoperatively, a poor vertebral bone quality has been observed.
      Efforts have been made to identify factors preventing curve progression, to
      optimize operational planning and to explain the pathomechanism. As part of the
      preoperative evaluation, the authors used a dual X-ray absorptiometry to assess
      the bone mineral density of the lumbar spine in 12 non operated patients with
      neurofibromatosis-1, supplemented by laboratory blood/urine investigations. A
      significant decrease in bone mineral density of lumbar spine was measured. An
      inverse relation was suggested between the severity of scoliosis and the lumbar
      spine Z-scores. No pivotal alterations were identified in the laboratory
      measurements. The bony tissue abnormality observed intraoperatively in
      neurofibromatosis-1 patients may be described as a diminution of the axial bone
      mineral density. The evaluation of bone mineral density in the course of the
      preoperative planning is proposed in neurofibromatosis-1.

PMID- 11828940
TI  - [Control of tachycardia with intravenous amiodarone in acute left heart failure].
AB  - The treatment of atrial tachycardia in critically ill patients can be difficult.
      Nine cases were presented with atrial tachyarrhythmias (mean heart rate > 130
      beats/min) and left heart failure. Congestive heart failure was diagnosed in 6
      patients (ejection fraction < 25%) and hypertensive heart failure in 3 patients
      (ejection infarction > 55%). The infusion of amiodarone (450 mg over 10 min and
      0.5 mg/min after the bolus administration) was associated with a decrease in
      heart rate 31 beats/min and an increase in systolic blood pressure of 13 mm Hg
      after one hour. There was only one adverse effect secondary to amiodarone
      therapy. In this case the sinus rhythm converted within 24 hours but T-waves
      alternans and short running torsade de pointes ventricular tachycardia was
      observed and amiodarone therapy was discontinued.

PMID- 11828941
TI  - [Diagnosis of cutaneous lymphomas].
AB  - Diagnosis of cutaneous lymphoma is based on the clinical picture and the
      histology. Several, different clinical entities are the members of this group
      with various clinical and histological features, with different course and
      prognosis. The clinical picture resembles that of a wide variety of benign,
      inflammatory dermatosis. The histological characteristics in the early lesions
      are not pathognomic, therefore immunohistochemistry and gene rearrangement
      studies are necessary to establish the diagnosis. These processes are evaluated
      in the article.

PMID- 11828942
TI  - [The language of anatomy in the 20th century].

PMID- 11828943
TI  - [In memory of Odon Borsos-Nachtnebel].

PMID- 11828944
TI  - Implications of adrenomedullin expression in the invasion of squamous cell
      carcinoma of the uterine cervix.
AB  - BACKGROUND: Adrenomedullin (AM) is a multifunctional peptide involved in a
      variety of physiological functions, including vasodilatation, growth regulation,
      and carcinogenesis. To elucidate the possible role of AM in the growth and
      invasion of uterine cervical carcinoma, the presence and distribution of AM and
      AM mRNA was examined in the neoplastic changes of squamous epithelium of the
      uterine cervix. METHODS: The expression of AM mRNA by CaSki, a uterine squamous
      cell carcinoma cell line, was examined by reverse transcriptase-polymerase chain
      reaction (RT-PCR). The presence and distribution of AM and AM mRNA in sections of
      normal cervical tissues, cervical intraepithelial neoplasia (CIN), and invasive
      squamous cell carcinomas were evaluated by immunohistochemical staining with a
      specific antibody against AM and by in situ RT-PCR, respectively. RESULTS: AM
      mRNA expression in CaSki cells was demonstrated by RT-PCR. Immunohistochemical
      staining for AM and in situ RT-PCR revealed that AM and AM mRNA were expressed in
      invasive squamous carcinoma cells, but not in normal cervical epithelium or in
      CIN lesions. Abundant expression of AM and AM mRNA was localized in the cytoplasm
      of carcinoma cells of bulky invasive carcinomas, while in early invasive
      carcinoma, the expression of AM and AM mRNA was more prominent in stromal cells
      adjacent to the early invasive carcinoma cells than in the carcinoma cells
      themselves. CONCLUSIONS: Because AM expression was evident only in invasive
      cervical squamous carcinoma cells and the stromal cells adjacent to early
      invasive carcinomas, it is likely that AM may play an important role in the
      growth and invasion of squamous cell carcinoma of the uterine cervix.

PMID- 11828945
TI  - Optimal doses of paclitaxel and carboplatin combination chemotherapy for ovarian
      cancer: a phase I modified continual reassessment method study.
AB  - BACKGROUND: A multicenter, phase I study of combination therapy with paclitaxel
      and carboplatin for epithelial ovarian cancer was conducted to determine the
      safety and recommended dosages for Japanese women. METHODS: Paclitaxel was
      administered intravenously over a 3-h period, followed by carboplatin
      administered intravenously over a 1.5-h period. A modified continual reassessment
      method (mCRM) was used in two treatment arms to establish the maximum tolerated
      dose (MTD) and recommended doses of the combination. In group A, the dose of
      paclitaxel (175 mg/m2) was constant and the dose of carboplatin was increased
      from 4 to 7 in terms of the target area under the plasma concentration-versus
      time curve (AUC). In group B, the dose of carboplatin was constant (AUC 6) and
      paclitaxel was administered at two dose levels (160 and 175 mg/m2). In both
      groups, the carboplatin dose was limited to a maximum of 800 mg/body for each
      administration. RESULTS: Because the calculated probability of toxicity was
      greatest at a dose of paclitaxel 175 mg/m2 and carboplatin AUC 7, this dose was
      designated the MTD in group A. Based on this result, treatment in group B was
      initiated at doses of paclitaxel of 160 mg/m2 and carboplatin AUC 6. While the
      dose of paclitaxel was escalated to 175 mg/m2, the safety of the combination was
      confirmed. The most frequent adverse effect was neutropenia, which resolved
      promptly with the appropriate use of granulocyte-colony stimulating factor (G
      CSF). No other severe hematologic or nonhematologic toxicities were observed.
      CONCLUSIONS: Our study demonstrated that the recommended dose for this
      combination regimen should be paclitaxel 175 mg/m2 plus carboplatin AUC 6
      (maximum dose, 800 mg/body).

PMID- 11828946
TI  - Combination chemotherapy of carboplatin and gemcitabine against solid tumors: a
      phase I trial.
AB  - BACKGROUND: Some trials have suggested that the combination of gemcitabine and
      platinum compounds can have a synergistic effect on several solid tumors, but, at
      present, the data concerning carboplatin-gemcitabine combinations are not
      sufficient to allow the planning of phase II trials. The present phase I trial
      was planned to define the maximum tolerated dose and the dose-limiting toxicity
      of a carboplatin-gemcitabine combination. METHODS: Thirty-two patients with
      advanced, pretreated solid tumors were treated with carboplatin on day 1 and
      gemcitabine on days 1, 8, and 15 every 28 days. The starting doses of carboplatin
      and gemcitabine were 3.5 mg/ml per min (area under the curve; AUC), and 600
      mg/m2, respectively. The doses of the two agents were alternately increased to 4,
      4.5, and 5 mg/ml per min and to 800 and 960 mg/m2, respectively. At each dose
      level, three patients were initially enrolled. If one of them experienced grade
      IV hematological toxicity or grade III-IV nonhematological toxicity (with the
      exception of alopecia), an additional three patients were enrolled at the same
      dose level. If two or more patients experienced grade IV hematological toxicity
      or grade III-IV non-hematological toxicity (with the exception of alopecia), the
      maximum tolerated dose was considered to have been reached, and the dose below
      this was recommended for further studies. All patients were evaluated weekly for
      toxicity and after every two courses of chemotherapy for response. RESULTS: Dose
      limiting toxicity was hematological, and the maximum tolerated doses were 4.5
      mg/ml per min for carboplatin and 800 mg/m2 for gemcitabine. The activity of the
      carboplatin/gemcitabine combination was encouraging, with a 21.9% response rate
      (7/32), three complete disease regressions, and a median time to progression of
      30 weeks. The gemcitabine doses of day 15 or days 8 and 15 were omitted for
      hematological toxicity in 57 (50%) and 17 (14.9%) courses of chemotherapy, while
      no courses of chemotherapy were delayed for grade III-IV hematological or
      nonhematological toxicity. CONCLUSION: The maximum tolerated doses suggested by
      this trial are lower than those in other similar phase I trials, but they are
      consistent with those reported by most of the trials investigating gemcitabine
      either in combination with cisplatin or in heavily pretreated patients.
      Carboplatin 4.5 mg/ml per min on day 1 plus gemcitabine 800 mg/m2 on days 1, 8,
      and 15 every 28 days may represent a promising schedule for further phase II
      trials.

PMID- 11828947
TI  - A study of the combination of gemcitabine hydrochloride (LY188011) and cisplatin
      in non-small-cell lung cancer: 3-week schedule.
AB  - BACKGROUND: It has been reported that the combination of gemcitabine (LY188011;
      GEM) and cisplatin (CDDP) in a 4-week schedule showed a high response rate for
      patients with non-small-cell lung cancer (NSCLC), but GEM could not be
      administered on day 15 because of increased myelosuppression in many patients.
      The present study was performed to evaluate the efficacy and safety of GEM and
      CDDP in a 3-week schedule. METHODS: Patients with unresectable NSCLC without
      prior chemotherapy were enrolled. We administered 1000 mg/m2 of GEM on days 1 and
      8, and 80 mg/m2 of CDDP on day 1. The feasibility of the combination therapy was
      confirmed in 8 patients, and then 20 more patients were enrolled, to evaluate the
      efficacy and safety of this combination therapy for all 28 patients. RESULTS: The
      response rate was 42.9% (12/28) and the median survival time was 12.6 months.
      Neutropenia, leukopenia, anemia, thrombocytopenia or lymphocytopenia of grade 3
      or higher were observed as hematological toxicity, and anorexia, nausea, fatigue,
      or vomiting of grade 3 were the nonhematological toxicities, but most of these
      toxicities were of grade 2 or less. For GEM and CDDP, 89% and 91% of the
      scheduled doses, respectively, were administered. CONCLUSION: This is the first
      study of the combination of GEM and CDDP with a 3-week schedule in Japan, and the
      results showed a low level of myelosuppression, high dose intensity, and high
      response rate, similar to the results reported in other countries. Accordingly,
      the combination of GEM and CDDP with a 3-week schedule may be a promising regimen
      for the treatment of NSCLC in Japan.

PMID- 11828948
TI  - Treatment of ruptured hepatocellular carcinoma.
AB  - BACKGROUND: The problem of whether surgical or conservative treatment is
      indicated for ruptured hepatocellular carcinoma (HCC) has not been analyzed from
      the viewpoint of long-term development of hepatitis viral infection from liver
      fibrosis to liver cirrhosis. Although transcatheter arterial embolization (TAE)
      for hemostasis followed by two-stage hepatectomy has been established as the best
      treatment for ruptured HCC, there still remain difficulties in the treatment of
      some patients. METHODS: Twelve patients with ruptured HCC who were surgically or
      conservatively treated were retrospectively analyzed in terms of modality of
      treatment, liver function, extension of HCC, complications, survival rate, and
      cause of death. RESULTS: Tumor rupture can occur either in the early phase or in
      the terminal phase during the development from liver fibrosis to liver cirrhosis,
      while tumor rupture occurs at the advanced stage in terms of HCC extension. TAE
      for emergent hemostasis or prevention of re-bleeding was performed in ten
      patients, while TAE was contraindicated in one patient and emergent laparotomy
      for hemostasis was performed in one patient. In four patients, elective extended
      surgical resection was performed, because liver function was evaluated as
      clinical stage 1 according to the General rules for the clinical and pathological
      study of primary liver cancer of the Liver Cancer Study Group of Japan. In seven
      patients, conservative or medical treatment was selected, because liver function
      was evaluated as poor. The surgically treated group, who could tolerate extensive
      operation, survived longer than the conservatively treated group. CONCLUSIONS:
      While TAE remains the best method to employ for hemostasis, it still has
      limitations. Hence, we should be mindful of other possible modalities for
      hemostasis and their outcomes. Rupture of HCC at an early phase in the
      development of liver fibrosis is a good indication for elective surgical
      treatment and should be distinguished from rupture in the terminal phase of liver
      cirrhosis, which should be treated conservatively. Although elective surgical
      treatment can be performed in selected patients, tumor size and location of HCC,
      in addition to liver function, should be taken into consideration.

PMID- 11828949
TI  - Double-blind randomized control trial of the effect of recombinant human
      erythropoietin on chemotherapy-induced anemia in patients with non-small cell
      lung cancer.
AB  - BACKGROUND: We studied the clinical effect of recombinant human erythropoietin (r
      huEPO) on anemia induced by two courses of cisplatin-based chemotherapy in
      patients with non-small cell lung cancer (NSCLC). METHODS: Seventy-two patients
      with NSCLC were randomized into three groups, receiving 100, or 200 IU/kg of r
      huEPO, or placebo. The r-huEPO and placebo were administered subcutaneously three
      times a week for 6 weeks, starting 2 weeks after the initiation of chemotherapy.
      RESULTS: In the 53 evaluable patients, hemoglobin (Hb) levels at the nadir after
      the second cycle of chemotherapy were significantly elevated compared with the
      nadir after the first cycle in both r-huEPO treated groups, while this level was
      decreased in the placebo group. Hb levels at the end of the second course of
      chemotherapy (week 8) in both r-huEPO groups were higher than that in the placebo
      groups. No adverse drug reaction attributable to r-huEPO was observed. Serum
      erythropoietin levels after the administration of r-huEPO were higher than those
      after placebo administration. CONCLUSIONS: r-huEPO had an effect in preventing
      anemia in patients with NSCLC who had cisplatin-based chemotherapy.

PMID- 11828950
TI  - Relapse patterns of localized non-Hodgkin's lymphoma of the head and neck after
      clinical remission: results of a strict follow-up procedure.
AB  - BACKGROUND: No effective follow-up strategy for non-Hodgkin's lymphoma (NHL) has
      been identified to date. The aim of this study was to assess the value of a
      strict follow-up procedure in patients with NHL after they showed clinical
      remission. METHODS: One hundred and twenty-one patients with localized NHL of the
      head and neck who had achieved clinical remission after radiation therapy and/or
      chemotherapy were followed with a strict follow-up strategy (consisting of a
      schedule of frequent office visits, imaging studies, and blood tests, even if the
      patient was asymptomatic). RESULTS: Thirty-nine patients relapsed after
      remission. Twenty-two (56.4%) of the relapses were associated with symptoms. In
      the 17 patients with asymptomatic relapses (43.6%), an abnormal physical
      examination result initially indicated relapse in 10 patients. The other tests
      that initially indicated relapse included scheduled computed tomography scans (3
      patients), scheduled gallium scans (2 patients), and serum lactate dehydrogenase
      levels (2 patients). According to the Ann Arbor stage at relapse, 72.7% of the
      patients with symptomatic relapses were stage III or IV, while 70.6% of the
      patients with asymptomatic relapses were stage I or II. CONCLUSIONS: These
      results indicate that a strict follow-up procedure is effective in detecting
      asymptomatic relapses, which generally involve a smaller tumor load than
      symptomatic relapses.

PMID- 11828951
TI  - Successful management of breast cancer with liver metastases with
      medroxyprogesterone acetate treatment.
AB  - A 38-year-old woman with cancer in the left breast underwent standard radical
      mastectomy. The estrogen receptor and progesterone receptor status of the primary
      tumor was unknown. Ten years after the surgery, a metastatic liver tumor was
      detected, and chemoendocrine therapy, consisting of cyclophosphamide, epirubicin,
      5-fluorouracil (CEF) and medroxyprogesterone acetate (MPA) was initiated. The
      metastatic liver tumor showed a partial response after 11 cycles of such
      chemoendocrine therapy. Subsequently, MPA alone was given daily as maintenance
      therapy, and the disease has remained stable for 6 years. For women with
      metastatic breast cancer, complete remission is uncommon, and stable disease is a
      reasonable goal of successful therapy. In this respect, chemoendocrine therapy
      with CEF and MPA, followed by MPA alone as maintenance therapy, was successful in
      the patient reported here. Importantly, the patient's quality of life has
      remained favorable for several years after the partial response was achieved.

PMID- 11828952
TI  - Should a lab report defective medical equipment?

PMID- 11828953
TI  - Talking with Albert Ziegler of Beckman Coulter. Interview by C. Anne Pontius.

PMID- 11828954
TI  - Avoiding specimen transportation errors.

PMID- 11828955
TI  - Are they microcytes or macrocytes? Can we do a better job?
AB  - As an attempt to improve accuracy in the grading of microcytes and macrocytes, a
      custom reticle was developed and evaluated. The evaluation looked at grading
      accuracy, reproducibility, speed, and opinion. In this study, the reticle
      improved the grading accuracy and reproducibility of graders who were "poorer
      performers." The reticle offered no advantage to the speed of the evaluation. The
      opinion survey indicated improved confidence with the reticle, and most of the
      participants found the device useful. The improvement to "poorer performers" is
      sufficient to warrant use in actual practice.

PMID- 11828956
TI  - Testing for genetic predisposition to venous thrombosis.

PMID- 11828957
TI  - Dealing with employee grief.

PMID- 11828958
TI  - Readers' perspectives. Within then next five years, at least 50% of U.S.
      physicians will use personal digital assistants.

PMID- 11828959
TI  - Intranet keeps eye on data.

PMID- 11828960
TI  - Netting managed care transactions.

PMID- 11828961
TI  - Army salutes use of Internet.

PMID- 11828962
TI  - Is the future in the palm of your hand?

PMID- 11828963
TI  - Industry consolidation hits a snag.

PMID- 11828964
TI  - Telemedicine begins to make progress.

PMID- 11828965
TI  - Technology to the rescue.

PMID- 11828966
TI  - Telemedicine takes aim at final frontier.

PMID- 11828967
TI  - Abstracts of the 2nd meeting of the Australasian Gene Therapy Society. April 27
      29, 2001. Sydney, Australia.

PMID- 11828968
TI  - Proceedings of the symposium on the cell cycle and development. London, United
      Kingdom, 11-13 April 2000.

PMID- 11828969
TI  - The Biological Availability of Aluminium: Sources, Sinks and Symptoms.
      Proceedings of the 4th Keele Meeting on Aluminium. 25-27 February 2001.

PMID- 11828970
TI  - Bibliography of toxinology.

PMID- 11828972
TI  - Abstracts of the annual meeting of the British Paediatric Neurology Association,
      2002.

PMID- 11828971
TI  - Special issue dedicated to the memory of Sergei Evgenievich Severin.

PMID- 11828973
TI  - Proceedings of the Physiological Society scientific meeting held at the Hungarian
      Academy of Science. Budapest, 27-29 May 2000.

PMID- 11828974
TI  - Stats & facts. Medicaid enrollment growth continues.

PMID- 11828977
TI  - Current readings in nuclear medicine.

PMID- 11828976
TI  - On the "concreteness" of risk: from epidemiometric epistemological realism to
      riskological ontology--to keep the ball rolling.

PMID- 11828975
TI  - Meeting highlights from 43rd annual meeting of the American Society of
      Hematology, December 7-11, 2001, Orlando, Florida and First International
      Congress on Monclonal Antibodies, August 30-September 2, 2001, Banff, Alberta,
      Canada.

PMID- 11828978
TI  - Delays, delays, even more delays.

PMID- 11828979
TI  - Ethical guidelines to publication of chemical research.

PMID- 11828981
TI  - TDA directory and membership roster 1999 - 2000.

PMID- 11828980
TI  - [Squamous cell carcinoma of the esophagus].

PMID- 11828983
TI  - Looking back: dental medicine over the past 100 years.

PMID- 11828984
TI  - Reflections. The experiences of a dental officer in World War II, 1943-1946.

PMID- 11828985
TI  - Gradual reappearance of post-hibernation circadian rhythmicity correlates with
      numbers of vasopressin-containing neurons in the suprachiasmatic nuclei of
      European ground squirrels.
AB  - European ground squirrels (Spermophilus citellus) in outside enclosures show
      suppressed circadian rhythmicity in body temperature patterns during the first
      days of euthermia after hibernation. This may reflect either gradual reappearance
      of circadian rhythmicity following suppressed functioning of the circadian system
      during hibernation, or it may reflect transient days during re-entrainment of the
      circadian system which, during hibernation, has drifted out of phase with the
      environmental light-dark cycle. Here we report that animals kept under continuous
      dim light conditions also showed absence of circadian rhythmicity in activity and
      body temperature in the first 5-15 days after hibernation. After post-hibernation
      arrhythmicity, spontaneous circadian rhythms re-appeared gradually and increased
      daily body temperature range. Numbers of arginine-vasopressin immunoreactive
      neurons in the suprachiasmatic nuclei correlated positively with individual
      circadian rhythmicity and increased gradually over time after hibernation.
      Furthermore, circadian rhythmicity was enhanced rather than suppressed after
      exposure to a light-dark cycle but not after a single 1-h light pulse (1,700
      lux). The results support the view that the functioning of the circadian system
      in the European ground squirrel is suppressed during hibernation at low
      temperatures and that it requires several days of euthermia to resume its summer
      function.

PMID- 11828986
TI  - Abstracts of the annual meeting of the Society for Adolescent Medicine. March 6
      10, 2002. Boston, Massachusetts, USA.

PMID- 11828987
TI  - [Medical and surgical treatment of uterine myoma. 1945].

PMID- 11828988
TI  - [Value of vaginal shedding cytology in the diagnosis of ovarian physiology and
      uterine cancer. 1946].

PMID- 11828989
TI  - Ellagic [correction of ellagica] acid inhibits arylamine N-acetyltransferase
      activity and DNA adduct formation in human bladder tumor cell lines (T24 and TSGH
      8301).
AB  - The fact that vitamin C (ascorbic acid) exhibits a protective effect in certain
      types of cancer is well documented. Our previous studies demonstrated that human
      bladder tumor cell line (T24) has N-acetyltransferase (NAT) activity in cytosols
      and intact cells. The present studies examined the inhibition of arylamine NAT
      activity and carcinogen (2-aminofluorene)-DNA adduct formation by ellagic acid
      (EA) in human bladder tumor cell lines (T24 and TSGH 8301). Two assay systems
      were performed, one with cellular cytosols (9,000 g supernatant), the other with
      intact bladder tumor cell suspensions. NAT activity and 2-aminofluorene-DNA
      adduct formation in T24 and TSGH 8301 cells was inhibited by EA in a dose
      dependent manner in both systems, i.e.. the greater the concentration of EA in
      the reaction the greater the inhibition of NAT activity (dose- and time-course
      dependent effects). The data also indicated that EA decreased the apparent Km and
      Vmax of NAT enzymes from T24 and TSGH 8301 cells in cytosols. NAT activity and 2
      aminofluorene-DNA adducts in T24 is higher than in TSGH 8301. This report is the
      first to demonstrate that EA affects human bladder tumor cell NAT activity.

PMID- 11828990
TI  - The genetic alterations in the oncogenic pathway of transitional cell carcinoma
      of the bladder and its prognostic value.
AB  - This review focuses on the main oncogenes studied in transitional cell carcinoma
      (TCC) in order to describe their mechanisms of action and investigate their
      possible prognostic value. Each oncogene family is reported following the order
      through which the proliferative signal is transduced from the extracellular space
      via a growth factor to the nucleus where transcription factors are switched on.
      Oncogenic activation at any level of the pathway will cause an increased
      transcription of genes enhancing the cell cycle, and proliferation will therefore
      be amplified. The main molecular or immunohistochemical studies from the
      literature on the aberrant expression of these genes are examined and compared
      with the aid of tables. Conclusions suggest that, although some may initially
      appear promising, no oncogene, has thus far been found to have a definite
      prognostic value superior to conventional grading and staging.

PMID- 11828991
TI  - Identification and functional study of phosphodiesterases in rat urinary bladder.
AB  - Abstract Cyclic nucleotides are important secondary messengers involved in
      modulating the contractility of various smooth muscles. Phosphodiesterases (PDE)
      play important roles in this process by modulating the levels of cyclic
      nucleotides and their duration of action. This study was designed to identify and
      characterize the PDE isoenzymes in rat urinary bladder and to evaluate their
      roles in regulating bladder smooth muscle tone. The involvement of cAMP and cGMP
      pathways in this process was also assessed. The studies were carried out with
      tissues from male and female rats and no significant sex-related difference was
      found in the results. Utilizing the unique pharmacological properties of
      different isoenzymes, PDE1, 2, 3, 4, and 5 were identified in rat bladder. Organ
      bath experiments showed that forskolin was most potent in relaxing pre-contracted
      rat bladder strips while sodium nitroprusside was moderately effective,
      suggesting the relaxation was mainly mediated by the cAMP pathway and that the
      cGMP pathway is moderately involved. For PDE inhibitors, the non-specific
      inhibitor papaverine was most effective in relaxing pre-contracted bladder
      strips. Among isoenzyme-selective inhibitors, vinpocetine, EHNA, and sildenafil
      induced more relaxation than milrinone and rolipram.

PMID- 11828992
TI  - P53 codon 72 polymorphism in bladder cancer--no evidence of association with
      increased risk or invasiveness.
AB  - We studied the effect of the p53 gene Arg72Pro polymorphism on bladder cancer
      susceptibility in a case control study of 121 bladder cancer patients and 114 age
      sex matched controls to determine whether this polymorphism is a biomarker for
      the risk and how aggressive the disease is. Genomic DNA was obtained from venous
      blood samples for genotype determination by PCR and restriction digestion. The
      genotype frequencies in the patient group were Arg/Arg: 0.3553, Arg/Pro: 0.4711,
      Pro/Pro: 0.1736, and in the control group Arg/Arg: 0.3684, Arg/Pro: 0.4825,
      Pro/Pro: 0.1491. The distribution of genotypes between the two groups was not
      statistically different (chi2 = 0.260, df: 2, P=0.878). The patient group was
      subdivided into two groups as superficial bladder cancer (n = 88) and invasive
      bladder cancer (n = 33), according to the presence of muscle invasion. The
      distribution of genotypes in the superficial group was Arg/Arg: 0.3409, Arg/Pro:
      0.5114, Pro/Pro: 0.1477 and in the invasive group Arg/Arg: 0.3940, Arg/Pro:
      0.3636, Pro/Pro: 0.2424. No association was observed with the invasiveness of the
      tumor (chi2 = 2.542, df 2, P = 0.281). Stratification of the data by tobacco
      exposure did not result in a significant difference in genotype frequencies.
      These data do not support an association between the p53 Arg72Pro polymorphism
      and bladder cancer.

PMID- 11828993
TI  - Photodynamic therapy in superficial bladder cancer: past, present and future.
AB  - For many reasons, such as toxicity and lack of selectivity of photosensitisers,
      as well as complexity of technical procedures and inconstant therapeutic results,
      photodynamic therapy of highly recurrent superficial bladder cancer never gained
      wide acceptance in the urological community. However, the 25 years of experience
      combined with the recent discovery of new photosensitisers, such as
      protoporphyrin IX (PpIX) induced by 5-aminolevulinic acid (ALA) or ALA
      derivatives or hypericin open new, very interesting perspectives in this
      therapeutic field.

PMID- 11828994
TI  - Sulindac inhibited gene expression and activity of arylamine N-acetyltransferase
      and DNA-2-aminofluorene adduct formation in T24 human bladder tumor cells.
AB  - We demonstrated in vivo that non-steroidal anti-inflammatory drugs including
      sulindac can act as inhibitors of urinary bladder carcinogenesis in rats. The aim
      of the present study was to determine whether sulindac affects arylamine N
      acetyltransferase (NAT) activity and gene expression and DNA-2-aminofluorene
      adduct formation in the T24 human bladder tumor cell line. The NAT activity (N
      acetylation of 2-aminofluorene) was measured by high performance liquid
      chromatography assaying for the amount of acetylated 2-aminofluorene and the
      remaining 2-aminofluorene (AF). The results demonstrated that NAT activity in T24
      cells were inhibited by the sulindac in a dose-dependent manner. The apparent
      values of Km and Vmax of NAT from T24 cells were also decreased by sulindac. This
      inhibition was not competitive. The amount of DNA-AF adduct formation in T24
      cells was also inhibited by sulindac. The data also demonstrated that sulindac
      inhibited the NAT mRNA level in T24 cells.

PMID- 11828995
TI  - Lack of evidence for the association of tumor necrosis factor-alpha gene promoter
      polymorphism with calcium oxalate stone and bladder cancer patients.
AB  - Urinary stone disease and bladder cancer are two of the most commonly seen
      urologic diseases in Taiwan. Tumor necrosis factor-alpha (TNF-alpha) is one of
      the cytokines secreted by macrophages and is related to a sequence of events in
      response to inflammation and cancer formation. We investigated the polymorphism
      of the TNF-alpha gene promoter -308 as a genetic marker in searching for the
      association between these two commonly seen urologic diseases. One hundred and
      fourteen patients with transitional cell carcinoma of the urinary bladder and 103
      patients with calcium oxalate stone were compared with 150 healthy controls. The
      polymorphism was detected by polymerase chain reaction-based restriction analysis
      (Nco I endonuclease). The results revealed no significant differences between
      normal individuals and the patients with the two commonly seen urologic diseases
      (P > 0.05). We concluded that the polymorphism of the TNF-alpha promoter -308 is
      not a valid genetic marker for these two urologic diseases.

PMID- 11828996
TI  - Hydroxyapatite induction and secondary aggregation of calcium oxalate, two
      important processes in calcium stone formation.
AB  - Stone formation has often been ascribed to crystal aggregation and fixed particle
      growth on kidney calcifications. In this paper, the influence of hydroxyapatite
      (HAP) and of preformed calcium oxalate (CaOx) aggregates on CaOx crystallization
      was studied in freshly voided urine. Crystallization was induced by different
      oxalate loads and precipitates were analyzed by the spectrophotometric
      measurement of sedimentation time (ST), which decreases with increasing particle
      size. The fact that the ST of aggregates (STA) is significantly lower than the ST
      of other particles demonstrates that STA is a useful indicator for aggregation.
      At relatively low oxalate loads the addition of HAP to urine increased STA by a
      factor of 4.3 (P < 0.001). After a second oxalate load, STA decreased by 56% (P <
      0.001), indicating secondary growth of the preexisting aggregates. HAP induced
      and primary CaOx aggregation occurred at low pH at which a high ionic calcium
      concentration (Ca2+) was measured. In urine, crystals are coated by
      macromolecules creating a negative surface potential with a consecutive
      accumulation of cations such as Ca2+. This Ca2+ accumulation could be responsible
      for the enhancement of aggregation by preexisting particles, which seems to be
      important for stone formation and which can otherwise hardly be explained in the
      presence of coated crystals.

PMID- 11828997
TI  - Differential involvement of reactive oxygen species and myeloperoxidase in oxygen
      dependent killing of urinary tract bacterial isolates by polymorphonuclear
      leukocytes.
AB  - We examined the involvement of reactive oxygen species (ROS) and myeloperoxidase
      (MPO) in bacterial killing by human polymorphonuclear leukocytes (PMN) by means
      of a chemiluminescence assay. Using four bacterial strains, including Pseudomonas
      aeruginosa strain ATCC 27853 and three other strains of P. aeruginosa that were
      isolated from patients with urinary tract infections, we examined whether the
      production of ROS and changes in MPO activity altered the numbers of bacteria in
      contact with PMN. For three strains (P. aeruginosa strain ATCC 27853, strain 40,
      and strain 64), a decrease in number of viable bacteria was observed with PMN
      addition over three 20-min intervals that differed significantly from
      observations in these strains without the addition of PMN, and residual MPO
      activity of these three strains correlated significantly with decreases in
      numbers of viable bacteria. We concluded that MPO-dependent processes are
      strongly favored by human PMN for the oxidative killing of bacteria.

PMID- 11828998
TI  - [Laparoscopic surgery of the colorectum: analysis of the results of the National
      Registry of the SICE].

PMID- 11828999
TI  - Acute toxicity of ferulenol, a 4-hydroxycoumarin isolated from Ferula communis L.
AB  - The acute LD50s of ferulenol were determined in albino mice by single po or ip as
      2,100 and 319 mg/kg bw, respectively. Ferulenol had a higher LD50 compared to
      warfarin and thus has a lower acute toxicity. Three days after ferulenol
      administration, dosed animals showed hypoprothrombinemia with internal and
      external hemorrhages similar to those described in ferulosys and anti-vitamin K
      experimental poisonings. Male mice were more sensitive to intoxication by
      ferulenol than were females.

PMID- 11829000
TI  - Interlaboratory reproducibility of mobility parameters in capillary
      electrophoresis for substance identification in systematic toxicological
      analysis.
AB  - An interlaboratory pilot study was performed to determine the reproducibility of
      mobility parameters in capillary zone electrophoresis (CZE) and micellar
      electrokinetic chromatography (MEKC). The study was performed by an intended
      small number of laboratories (three) that used different brands of instruments
      (two). The effective mobility was corrected using standards by a method that was
      recently introduced to obtain a more reproducible migration parameter. A test set
      of 20 acidic test compounds and 5 reference compounds were analyzed during five
      days in each laboratory using CZE and MEKC. Buffers used consisted of 90 mM
      borate set at pH 8.4 (CZE) and 20 mM phosphate, 50 mM sodium dodecyl sulfate set
      at pH 7.5 (MEKC). Analyses were carried out using fused-silica capillaries at an
      electric field strength of either 52.6 kV/m or 37.5 kV/m. The interlaboratory
      reproducibility (mean RSD) of the effective mobility was 3.0% for CZE and 6.7%
      for MEKC. After applying the correction method, these values became 3.0% for CZE
      and 3.3% for MEKC, which is adequate for systematic toxicological analysis (STA)
      applications. A significant improvement of reproducibility for the calculated
      corrected effective mobility mu(eff)c was observed when variations are high.
      Therefore, it is recommended to use the correction method in interlaboratory
      situations, especially when instruments and capillaries from different
      manufacturers are used.

PMID- 11829001
TI  - Aspirin gets a tentative nod.

PMID- 11829002
TI  - Rapid method for the determination of total 5-methyltetrahydrofolate in blood by
      liquid chromatography with fluorescence detection.
AB  - A liquid chromatographic method is described for the determination of total 5
      methyltetrahydrofolate (5-MTHF) in whole-blood samples. The method was applied to
      a survey of whole-blood total 5-MTHF levels of women at child-bearing age. To
      determine whole-blood total 5-MTHF content, a whole-blood sample was frozen and
      thawed to break red blood cells and the 5-MTHF polyglutamates were released and
      hydrolyzed into 5-MTHF monoglutamate by endogenous polyglutamates hydrolase in
      the plasma. In brief, an aliquot of 0.1 ml whole-blood sample was mixed with 0.3
      ml 57 mmol/l ascorbic acid and incubated at 37 degrees C for 60 min, then diluted
      with 0.6 ml buffer solution (0.2 mol/l potassium phosphate dibasic and 30 mmol/l
      mercaptoethanol, pH 8.5). After the sample was heated at 100 degrees C for 10 min
      and centrifuged, the supernatant was analyzed by reversed-phase liquid
      chromatography with fluorescence detection. The recoveries from spiked samples
      were from 95 to 105% with within-day and day-to-day relative standard deviations
      less than 6.5%. The detection limit was estimated to be 30 nmol/l based on three
      times the noise level (peak to peak). Application of the method to a survey of
      whole-blood total 5-MTHF levels of women at child-bearing age showed that the
      method was reliable and suitable for the determination of blood total 5-MTHF.

PMID- 11829003
TI  - Liquid chromatographic determination of isoniazid, pyrazinamide and rifampicin
      from pharmaceutical preparations and blood.
AB  - Isoniazid (IN), pyrazinamide (Pz) and rifampicin (Rf) are separated on YMC-ODS
      column. IN was derivatized with 2-fluorene-carboxaldehyde (FA). The separation
      was achieved using ethanol-chloroform-acetonitrile water by isocratic elution and
      detected at 337 nm. The detection limits were 0.11 ng, 0.2 ng and 13 ng/injection
      (5 microl) for IN, Pz and Rf, respectively. The method of analysis was applied to
      the pharmaceutical preparations and in the blood samples of the patients
      suffering from tuberculosis after undergoing chemotherapy with IN, Pz and Rf. The
      amounts quantitated in blood showed 0.97 to 1.58 microg/ml IN, 3.44 to 4.09
      microg/ml Pz and 1.98 to 3.5 microg/ml Rf with coefficient of variations 0.8
      1.8%, 0.9-1.3% and 0.8-2.1%, respectively.

PMID- 11829005
TI  - American Academy of Allergy, Asthma and Immunology 58th annual meeting. New York,
      New York, USA. March 1-6, 2002. Abstracts.

PMID- 11829004
TI  - Nephrology: 1. Investigation and treatment of recurrent kidney stones.

PMID- 11829006
TI  - The influence of high contrast acuity and normalised low contrast acuity upon
      self-reported situation avoidance and driving crashes.
AB  - The aim of this study was to determine the cues used to signal avoidance of
      difficult driving situations and to test the hypothesis that drivers with
      relatively poor high contrast visual acuity (HCVA) have fewer crashes than
      drivers with relatively poor normalised low contrast visual acuity (NLCVA). This
      is because those with poorer HCVA are well aware of their difficulties and avoid
      dangerous driving situations while those poorer NLCVA are often unaware of the
      extent of their problem. Age, self-reported situation avoidance and HCVA were
      collected during a practice based study of 690 drivers. Screening was also
      carried out on 7254 drivers at various venues, mainly motorway sites, throughout
      the UK. Age, self-reported situation avoidance and prior crash involvement were
      recorded and Titmus vision screeners were used to measure HCVA and NLCVA.
      Situation avoidance increased in reduced visibility conditions and was influenced
      by age and HCVA. Only half of the drivers used visual cues to signal situation
      avoidance and most of these drivers used high rather than low contrast cues. A
      statistical model designed to remove confounding interrelationships between
      variables showed, for drivers that did not report situation avoidance, that crash
      involvement decreased for drivers with below average HCVA and increased for those
      with below average NLCVA. These relationships accounted for less than 1% of the
      crash variance, so the hypothesis was not strongly supported.

PMID- 11829007
TI  - Paediatric community vision screening with combined optometric and orthoptic
      care: a 64-month review.
AB  - We report a new model of community-based secondary vision screening and
      demonstrate that a high proportion of children can be effectively managed in such
      a clinic without referral to the hospital eye service (HES). We performed a 64
      month retrospective study of a secondary vision screening clinic providing the
      combined skills of an optometrist and orthoptist in a community setting.
      Particular attention was given to the diagnosis and management of children not
      referred to the HES. During this period, 1755 children were sent appointments and
      74% (1300) attended the clinic. The community orthoptist and school nurses
      referred 53% of the patients and health visitors, general practitioners and
      community medical officers made 32% of the clinic referrals. Spectacles were
      prescribed for 41% of the children and 8% were prescribed patching. Sixteen per
      cent of the children were referred on to the HES. This model of care using the
      combined expertise of the orthoptist and optometrist is able to diagnose and
      manage the majority of children who have failed primary vision screening and
      avoids unnecessary referrals to the HES.

PMID- 11829008
TI  - Randomised controlled trial of the effect of coloured overlays on the rate of
      reading of people with specific learning difficulties.
AB  - A randomised controlled trial has demonstrated that, for selected children with
      reading difficulties, individually prescribed coloured filters reduce symptoms of
      asthenopia. In the present study, we investigate the effect of individually
      prescribed coloured overlays on the rate of reading. Subjects were 33 children
      and adults who: had consulted a specific learning difficulties clinic; had
      received treatment to normalise any conventional optometric and orthoptic
      anomalies; and subsequently reported symptomatic relief from coloured filters.
      These subjects carried out the Wilkins Rate of Reading Test (which assesses
      visual rather than linguistic factors) under two conditions: with their chosen
      coloured overlay and with a control filter. Steps were taken to ensure that a
      strong placebo effect was associated with the control overlay and, when asked
      which they preferred, subjects were not significantly more likely to prefer their
      coloured overlay than the control filter (p=0.11). Nonetheless, the rate of
      reading was significantly faster with the coloured overlay than with the control
      (p=0.0019). Further analyses support the conclusion that individually prescribed
      coloured filters can improve reading performance for reasons that cannot be
      solely attributed to conventional optometric factors or to placebo effects.

PMID- 11829009
TI  - Do tinted lenses or filters improve visual performance in low vision? A review of
      the literature.
AB  - This is a review of studies that have investigated the proposed rehabilitative
      benefit of tinted lenses and filters for people with low vision. Currently, eye
      care practitioners have to rely on marketing literature and anecdotal reports
      from users when making recommendations for tinted lens or filter use in low
      vision. Our main aim was to locate a prescribing protocol that was scientifically
      based and could assist low vision specialists with tinted lens prescribing
      decisions. We also wanted to determine if previous work had found any tinted
      lens/task or tinted lens/ocular condition relationships, i.e. were certain tints
      or filters of use for specific tasks or for specific eye conditions. Another aim
      was to provide a review of previous research in order to stimulate new work using
      modern experimental designs. Past studies of tinted lenses and low vision have
      assessed effects on visual acuity (VA), grating acuity, contrast sensitivity
      (CS), visual field, adaptation time, glare, photophobia and TV viewing. Objective
      and subjective outcome measures have been used. However, very little objective
      evidence has been provided to support anecdotal reports of improvements in visual
      performance. Many studies are flawed in that they lack controls for investigator
      bias, and placebo, learning and fatigue effects. Therefore, the use of tinted
      lenses in low vision remains controversial and eye care practitioners will have
      to continue to rely on anecdotal evidence to assist them in their prescribing
      decisions. Suggestions for future research, avoiding some of these experimental
      shortcomings, are made.

PMID- 11829011
TI  - Proceedings of the 2001 Spring Meetings of the WPSA French and WPSA United
      Kingdom Branches.

PMID- 11829010
TI  - Effects of toxic dinoflagellate Alexandrium tamarense on the energy budgets and
      growth of two marine bivalves.
AB  - Harmful algal blooms (HAB) may impose a serious threat to aquatic lives and human
      health. We determined the effects of a toxic dinoflagellate Alexandrium tamarense
      (clone ATCIO1, isolated from Hong Kong coastal waters) on the energy budget,
      quantified as scope for growth (SFG), and the growth rate of the manila clam
      Ruditapes philippinarum and the green-lipped mussel Perna viridis. To quantify
      the SFG, clams and mussels were dosed with different amounts of toxic A.
      tamarense for 6 days, resulting in different toxin burdens in the tissues.
      Clearance rate, absorption efficiency, and respiration rate were subsequently
      measured in these toxin containing bivalves. Clearance rate significantly
      declined at the highest toxin burden in the clams only, while there was no
      significant difference in the clearance rate among different treatments for the
      mussels. The respiration rate of either bivalve was not significantly affected by
      toxin accumulation in the tissues. In contrast, the absorption efficiency of both
      clams and mussels decreased, in a concentration-dependent manner for mussels but
      not for clams, when the tissue accumulated the toxins. With an increase in
      paralytic shellfish poisoning (PSP) toxin burden, SFG in both clams and mussels
      was significantly reduced, primarily because of the decrease of absorption
      efficiency. The growth rate of juvenile clam R. philippinarum, measured as an
      increment in tissue dry weight over a 15 d exposure period, was significantly
      lower during their feeding on toxic dinoflagellate than the growth rate of clams
      feeding on the diatom Thalassiosira pseudonana. The juvenile mussel P. viridis,
      however, exhibited similar growth rates after feeding on the toxic
      dinoflagellates and the nontoxic diatom. This study showed that SFG can provide a
      sensitive and integrated measure of the effect of HAB on the physiology of
      bivalves. Clam R. philippinarum may be more sensitive, in terms of their energy
      budget, to PSP toxin accumulation than the mussel P. viridis.

PMID- 11829012
TI  - Current status of diabetes treatment.

PMID- 11829013
TI  - Chronic complications of diabetes.

PMID- 11829014
TI  - Immunohistochemical detection of salivary agglutinin/gp-340 in human parotid,
      submandibular, and labial salivary glands.
AB  - Salivary agglutinin is a Streptococcus mutans binding protein and a member of the
      scavenger receptor cysteine-rich superfamily. It is identical to lung gp-340 and
      brain DMBT1, which possibly play a role in innate immunity and tumor suppression,
      respectively. The goal of this study was to localize salivary agglutinin in human
      salivary glands. Two monoclonal antibodies, directed against gp-340, were
      characterized. mAb 213-1 reacted with sialic acid epitopes and cross-reacted with
      MUC7. The reaction with mAb 213-6 disappeared after reduction, suggesting that a
      protein epitope was recognized. In the parotid gland, immunohistochemical
      labeling with mAb 213-6 was found in the duct cells. In the submandibular gland
      and labial gland, both serous acini and demilune cells were labeled. In the
      labial gland, labeling was found at the luminal side of the duct cells. Salivary
      agglutinin was distinctly localized in salivary glands, but in distinct glandular
      secretions, no differences in electrophoretic behavior were observed.

PMID- 11829015
TI  - DNA hybridization arrays for gene expression analysis of human oral cancer.
AB  - DNA hybridization arrays permit global gene expression profiling to be done in a
      single experiment. The evolution and challenges of DNA hybridization arrays are
      reflected in the variety of experimental platforms, probe composition,
      hybridization/signal detection methods, and bioinformatic interpretation. In
      tumor biology, DNA hybridization arrays are being used for gene/gene pathway
      discovery, diagnosis, and therapeutic design. Similar applications are advancing
      our understanding of oral cancer cell biology.

PMID- 11829016
TI  - [The Arabic pharmacology and the introduction to Europe: the background of the
      Arabic pharmacology - the legacy from Greece].
AB  - When the Arabic-Islamic medicine evolved partly as a consequence of the wave of
      translations from mainly Greek medical books to Arabic in the 9th century the
      pharmacological works, which were available, were also translated. The books of
      Dioscurides and Galen on pharmacological matters became the decisive books of
      pharmacological translated literature and they formed the basis of the
      pharmacological understanding in the subsequent extensive literature on
      pharmacognosy and pharmacology written in Arabic. Nevertheless the Arabs united
      these two disciplines in a regular pharmacy and they evolved it as an independent
      discipline, which although attached to medicine was regarded as having its own
      praxis. The physicians and scientists rationalized and systematized their
      knowledge of medicinal plants and drugs and extended their knowledge by using
      original observations and research. Many books on medicaments were written, both
      as materia medica, i.e. records on simple drugs, and dispensatories, i.e. books
      on compounded drugs. These two kinds of books were always written separately as
      they were seen by the Arabs themselves as pertaining to two different
      subdisciplines, which meant that they were separated too in independent chapters
      or books in general Arabic works on medicine. When the extensive translations of
      Arabic medical literature to Latin took place in Italy and Spain in the 11th and
      12th centuries, the Arabic pharmacological literature was of course also
      translated, and its decisive influence on later medieval European medical
      writings is easy to demonstrate. In the 18th century Peter Forsskaal was one of
      the first Europeans in the modern scientific tradition to collect and make notes
      on drugs used in Cairo and in Yemen.

PMID- 11829017
TI  - [Henri Dunant, Geneve-Convention and Red Cross: a historical view].
AB  - Several appalling reports throughout the ages are at hand concerning the inhuman
      treatment of the wounded persons at the battlefields where they were left without
      any help, killed and maybe taken away as slaves. Not until Napoleon's time there
      was from military as well as civil side raised claim on the human treatment and a
      real sanitary service. The demands were advanced with weight of persons like
      Larrey, Dufour adn Dunant, who was the prime mover in all the efforts, at last
      leading to his "Un Souvenir de Solferino", which helped making the way for the
      Geneve-Convention 22. August 1864, and afterwards the foundation of the Red
      Cross, thus as we today know it as the biggest international relief-organization
      in the world.

PMID- 11829018
TI  - Genomic logic, allelic inference, and the functional classification of genes.

PMID- 11829019
TI  - Function-morphological investigations of fish inner ear otoliths as basis for
      interpretation of human space sickness.
AB  - In man, altered gravity may lead to a vestibular dysfunction causing space motion
      sickness. A hypothesis was developed, according to which asymmetric inner ear
      statoliths might be the morphological basis of space sickness. The animal model,
      fish, revealed further information: inner ear "stone" (otolith) growth is
      dependent on the amplitude and the direction of gravity, regulated by a negative
      feedback mechanism. The present study was focused on the question, where the
      regulation centre of adaptive otolith growth may be situated. Therefore, the
      vestibular nerve was unilaterally transected in neonate swordtail fish
      (Xiphophorus helleri). As growth marker, the calcium tracer alizarin-complexone
      was used. It was found that otolith growth had ceased on the operated head sides
      indicating that the brain is significantly involved in regulating otolith growth.
      About 2 weeks after nerve transection, otoliths had regained normal growth,
      probably due to nerve regeneration. Concerning fish, it has now to be tested, if
      this regeneration is affected by altered gravity, e.g. in a long-term experiment
      on the International Space Station. Regarding mammals, it has to be proved if
      asymmetric statoliths are the basis of kinetosis and whether or not the mammalian
      brain has an effect on statolith growth in the course of compensating altered
      gravity.

PMID- 11829021
TI  - Communication with extraterrestrial intelligence. Special issue.

PMID- 11829020
TI  - Inhibition of gravitropism in oat coleoptiles by the calcium chelator,
      ethyleneglycol-bis-(beta-aminoethyl ether)-N,N'-tetraacetic acid.
AB  - A treatment period as brief as 8 h in 10(-3) M EGTA completely blocks
      gravitropism in 70-80% of the treated coleoptiles of oats (Avena sativa L. cv.
      Garry) without inhibiting growth. Only about 10% of the plants perfused in water
      failed to exhibit gravitropism. Subsequent perfusion of EGTA-treated plants with
      calcium completely restores gravitropism; post-perfusion with water does not.
      After perfusion in water for 10 h, gravistimulated oat coleoptile segments show
      the same asymmetry of 45Ca distribution as reported earlier for non-perfused
      coleoptiles and sunflower hypocotyls. The degree of this asymmetry is reduced in
      those coleoptiles partially inhibited by perfusion in EGTA and is essentially
      absent in those coleoptiles completely inhibited by EGTA. The fact that calcium
      reverses the inhibitory effects of EGTA on gravitropism indicates that the
      inhibition was probably due to a reduction in the availability of free calcium
      required for one or more of the transduction steps of gravitropism.

PMID- 11829022
TI  - Life support system with autonomous control employing plant photosynthesis.
AB  - This research was aimed at obtaining a closed control system. This was achieved
      by placing all the technological processes providing for human vital activities
      within the hermetically sealed space, and by transferring the entire control and
      guidance of these processes to people inhabiting the system. In contrast to
      existing biological life support systems, man has been included not only as a
      participant of metabolism, but as an operator who is the central figure in
      collecting information, making decisions and controlling all technological
      processes. To tackle this problem, the "BIOS-3" experimental complex was created
      for performing long-term experiments using different structures of biological
      life-support system. The experiment lasted six months and consisted of three
      stages. During the first stage the system was comprised of two equivalent
      phytotrons with the culture of wheat and an assortment of vegetable plants, and
      the living compartment. At the second stage, one of the phytotrons was removed
      while a compartment of chlorella cultivators was introduced. The third stage
      differed from the second, the former using wheat phytotron and the latter
      employing phytotron with an assortment of vegetable cultures. Three men inhabited
      the system simultaneously. The experiment demonstrated that a biological life
      support system controlled autonomously from the inside is feasible within a small
      confined space. However, immunological and microbiological research shows, that
      the medium created by the system is not fully adequate for man. In conclusion,
      some prospects have been outlined for further studies of biological life support
      systems.

PMID- 11829023
TI  - Cardiorespiratory responses to exercise after bed rest in men and women.
AB  - The purpose of this study was to compare cardiorespiratory responses of men and
      women to submaximal and maximal workloads before and after bed rest (BR). Fifteen
      male college students (19-23 yr) and 8 female nurses (23-34 yr) underwent 14 d
      and 17 d, respectively of bed rest. The maximal work capacity test was performed
      in the supine position on a bicycle ergometer just before and immediately after
      bed rest. The women's maximal O2 uptake (maximal VO2) was 41% lower (P<0.05) than
      the men's before bed rest and 42% lower (P<0.05) after bed rest. During bed rest
      the women's maximal VO2 decreased from 2.06 to 1.86 liter/min (-9.7%, P<0.05),
      and that of the men decreased from 3.52 to 3.20 liter/min (-9.1%, P<0.05).
      Compared with pre-BR values, after bed rest the maximal ventilatory volume was
      essentially unchanged in the men (+1.8%) and women (+ 2.3%), but maximal heart
      rate was elevated from 185 to 193 b/min (+ 4.3%, P<0.05) in the men and from 181
      to 187 b/min (3.3%, P<0.05) in the women. Submaximal VO2 was unchanged after bed
      rest in the men but was significantly reduced in the women; the women's Hct and
      RBC levels were lower (P<0.05) than comparable male data. Mean corpuscular volume
      was unchanged in both groups pre- and post-bed rest. It is concluded that the
      proportional deterioration in maximal VO2 following prolonged bed rest was
      essentially the same in young men and women.

PMID- 11829024
TI  - Space motion sickness medications: interference with biomedical parameters.
AB  - The possibility that drugs administered to Skylab 3 (SL-3) and 4 (SL-4) crewmen
      for space motion sickness may have interfered with their biomedical evaluation in
      space was investigated. Healthy volunteers received combinations of
      Scopolamine/Dexedrine for four days in regimens similar to those used in these
      missions. Urine samples, heart rate, body temperature, mood and performance were
      analyzed for drug-related changes. Twenty-four hour urine samples were analyzed
      by the same procedures as those used to analyze the flight samples. Hormone
      concentrations determined included cortisol, epinephrine, norepinephrine,
      aldosterone and antidiuretic hormone (ADH). In addition, volume, specific
      gravity, osmolarity, sodium (Na), potassium (K), calcium (Ca), magnesium (Mg),
      chloride (Cl), inorganic phosphate, uric acid and creatinine were measured.
      Performance was not affected by the Scopolamine/Dexedrine. The drug combination
      increased daily mean heart rate (HR) significantly in all the subjects and daily
      mean rectal temperature (RT) in some of the subjects. A 2-4 hr phase shift in the
      HR circadian rhythm was also observed which indicates that internal circadian
      synchrony was disturbed by the drugs. Psychological and subjective evaluation
      indicated that the subjects could usually identify which days they were given the
      drugs by an increase in tension and anxiety, decreased patience, restlessness,
      decreased appetite, difficulty in sleeping and feelings of increased heart rate
      and body temperature. Urinary electrolytes were not changed significantly by the
      drug, but marked and significant changes occurred in urine volume and hormone
      excretion patterns. Scopolamine/Dexedrine caused consistent elevations in urinary
      cortisol and epinephrine and a transient elevation in ADH. Norepinephrine
      excretion was decreased, but there was no significant change in aldosterone
      excretion or in 24 hr urine volume. A comparison of these findings with the first
      four days of inflight data from the SL-3 and SL-4 missions leads to the
      conclusion that the dramatic increases in aldosterone excretion during the first
      three days of spaceflight probably can be directly attributed to weightlessness,
      whereas the antimotion sickness medication could have substantially contributed
      to the early increased excretion of epinephrine and cortisol during these
      missions.

PMID- 11829025
TI  - Amendment of regulations regarding certain label statements on prescription
      drugs. Final rule.
AB  - The Food and Drug Administration (FDA) is amending its regulations concerning
      certain statements that have been required on the labels of prescription drugs
      generally and on certain narcotic or hypnotic (habit-forming) drugs. The agency
      is taking this action in accordance with provisions of the Food and Drug
      Administration Modernization Act of 1997 (Modernization Act).

PMID- 11829026
TI  - Standard formatting unifies patient records across medical disciplines.

PMID- 11829027
TI  - Positive control material introduced to ASTM Hemolysis Standard.

PMID- 11829028
TI  - Revised ASTM Standard offers solid endoscope reprocessing protocol to GI
      community.

PMID- 11829029
TI  - Draft standards for nitinol alloys present optimum medical device design
      processes.

PMID- 11829030
TI  - Surgical fires addressed in new guide.

PMID- 11829031
TI  - Standard defines optimum reprocessing of endoscopic accessory instruments.

PMID- 11829032
TI  - Histologic evaluation of threaded HA-coated root-form implants after 3.5 to 11
      years of function: a report of three cases.
AB  - This article presents a histologic evaluation of three hydroxyapatite (HA)-coated
      root-form implants retrieved from humans after being in function for 3.5 to 11
      years. If the coronal portion, where bone loss was observed clinically and
      radiographically, is excluded, all implants appeared to be well osseointegrated,
      with intimate contact between the surrounding bone and the coating. There was no
      sign of resorption or dissolution of the HA coating. The coating had a uniform
      thickness (50 microm) equal to the thickness originally provided by the
      manufacturer In the few areas where there was no bone contact, the HA coating
      appeared to line the implant with no sign of dissolution. The few detached
      particles had tight contact with the bone, demonstrating the biocompatibility of
      the HA. The observations from the three reported cases suggest that the HA
      coating of dental implants may not be susceptible to resorption or dissolution
      under long-term function.

PMID- 11829033
TI  - A bioresorbable barrier in the treatment of gingival recession: description of a
      new resorbable dome device.
AB  - The biologic principle of guided tissue regeneration has been expanded to
      mucogingival surgery, using resorbable barrier membranes for the treatment of
      gingival recessions. Space provision is one of the main problems in non-space
      making defects, considering the softness of resorbable membranes. In this study,
      we tested the possibility to create and maintain a secluded space using a slow,
      long-lasting resorbable suture so that a resorbable dome device could support the
      barrier and immediately become a space-making device. Ten purely mucogingival
      recessions in ten patients were treated. At 12 months, the results were
      evaluated. In five subjects the gingival margin was within 1 mm of the
      cementoenamel junction, in four patients it was within 2 mm, and in one case a
      residual gingival recession was present (where the membrane became exposed). The
      mean root coverage obtained was 70.4%, while the mean gain of clinical attachment
      was 3.3 mm.

PMID- 11829034
TI  - Effect on bone healing of bone morphogenetic protein placed in combination with
      endosseous implants: a pilot study in beagle dogs.
AB  - Although dental implants have become an effective treatment modality for the
      replacement of missing teeth, their predictability relies on successful
      osseointegration during the healing period. The purpose of this pilot study was
      to evaluate the effect of recombinant human bone morphogenetic protein-2 (rhBMP
      2) on early bone formation within the perforations of dental implants in beagle
      dogs. Histologic sections were evaluated for the extent of new bone formation
      within a 1-mm diameter of through-and-through perforations. Data indicated that
      significantly more bone formation occurred with rhBMP-2-treated sites within the
      implant perforation (P < 0.01) compared to sites treated with the vehicle alone.
      This pilot study indicates that rhBMP-2 increases the rate and extent of bone
      formation in combination with dental implants.

PMID- 11829035
TI  - A tissue engineered cell-occlusive device for hard tissue regeneration--a
      preliminary report.
AB  - Tissue engineering is an emerging discipline that applies engineering principles
      to create devices for the study, restoration, modification, and assembly of
      functional tissues and organs from native or synthetic sources. In the field of
      guided bone regeneration (GBR), cellular matter engineering has been applied,
      more or less successfully, to the development of biodegradable and bioresorbable
      devices with chemical, physical, or mechanical properties, structure, or form
      that permit active tissue integration with desirable cell types and tissue
      components. The employment of synthetic and naturally occurring polymers as well
      as sophisticated manufacturing technologies allow the tissue engineering of
      matrix configurations so that the biophysical limitations of mass transfer can be
      satisfied. The configuration of such a hybrid matrix can also be manipulated to
      vary the surface area available for cell attachment, as well as to optimize the
      exposure of the attached cells to nutrients. A biodegradable and bioresorbable
      device made of synthetic and natural polymers was engineered specifically for GBR
      procedures. The degradation and resorption kinetics as well as the mechanical
      properties give the device the potential to function as a carrier for bone growth
      factors. This innovative device was applied as a GBR membrane in a clinical
      investigation in seven patients.

PMID- 11829036
TI  - A new approach to continuing education.

PMID- 11829037
TI  - The distal extension case: an alternative restorative design for implant
      prosthetics.
AB  - A restorative design is introduced in preference to the implant-supported bar,
      clip, or ball-type removable prosthesis. It has been necessary to develop an
      alternative treatment approach to the placement and restoration of implants in
      the posterior mandible or maxilla. In an examination of the available therapeutic
      choices and their rationales, this treatment option offers greater function,
      esthetics, and comfort. Four maxillary and one mandibular arches were
      reconstructed with anterior implant-supported fixed bridges/splinted restorations
      and a precision partial denture design posteriorly, using an extracoronal
      universal ball attachment. These cases have demonstrated minimal maintenance up
      to 7 years in function.

PMID- 11829039
TI  - Connective tissue grafting employing the tunnel technique: a case report of
      complete root coverage in the anterior maxilla.
AB  - Techniques for surgical root coverage have been continuously revised over the
      past few decades. With increased knowledge on the etiopathogenesis of gingival
      recessions and on the repair/regeneration mechanisms of deep and superficial
      periodontal tissues, procedure simplification has been possible, and more
      predictable and stable results have been obtained. The maintenance of maximal
      blood supply has brought major changes in flap design. The coverage of contiguous
      recessions on the maxillary central incisors using a conservative technique for
      the incision of the recipient site is presented, along with the 11-month follow
      up from surgery. A supraperiosteal tunnel was performed for the insertion and
      stabilization of a connective tissue autograft.

PMID- 11829038
TI  - Gingival augmentation with an acellular dermal matrix: human histologic
      evaluation of a case--placement of the graft on bone.
AB  - The importance of gingival augmentation to increase the amount of keratinized
      tissue is a controversial subject. In this case report, an acellular dermal
      matrix was used to obtain an increase in the amount of keratinized tissue around
      four implants. In this case, the acellular dermal matrix was placed on bone. The
      surgical procedure resulted in an increase in the amount of keratinized tissue.
      Therefore, it met the clinical goals of the surgical procedure. However, the
      clinical findings and patient pain levels during the healing seemed to resemble a
      denudation procedure. Additionally, the histologic evaluation of the tissue that
      formed around the implants showed that the acellular dermal matrix was not
      incorporated into the result. Based on this case, the use of an acellular dermal
      matrix placed on bone does not seem to be a good technique to increase the amount
      of keratinized tissue.

PMID- 11829040
TI  - Pemphigus vulgaris: clinicopathologic review of 33 cases in the oral cavity.
AB  - A retrospective study was conducted on all cases of pemphigus vulgaris occurring
      on oral mucosal surfaces in the files of the Oral Pathology Laboratory at Temple
      University from 1974 to 1996. A total of 35 biopsies from 33 patients were
      reviewed, 25 female and eight male. Patient ages ranged from 27 to 79 years; the
      mean age was 56.5. The most common clinical complaint was of painful ulcers that
      failed to resolve within several weeks. Thirty patients had no known history of
      pemphigus, while in three patients a history of pemphigus was known. The most
      common clinical impression was that of mucous membrane pemphigoid, but the
      differential diagnosis included other vesiculoerosive conditions.

PMID- 11829041
TI  - Rapid orthodontics with alveolar reshaping: two case reports of decrowding.
AB  - Two case reports demonstrate a new orthodontic method that offers short treatment
      times and the ability to simultaneously reshape and increase the buccolingual
      thickness of the supporting alveolar bone. A 24-year-old man with a Class I
      severely crowded malocclusion and an overly constricted maxilla with concomitant
      posterior crossbites and a 17-year-old female with a Class I moderately to
      severely crowded malocclusion requested shortened orthodontic treatment times.
      This new surgery technique included buccal and lingual full-thickness flaps,
      selective partial decortication of the cortical plates, concomitant bone
      grafting/augmentation, and primary flap closure. Following the surgery,
      orthodontic adjustments were made approximately every 2 weeks. From bracketing to
      debracketing, both cases were completed in approximately 6 months and 2 weeks.
      Posttreatment evaluation of both patients revealed good results. At approximately
      15 months following surgery in one patient, a full-thickness flap was again
      reflected. Visual examination revealed good maintenance of the height of the
      alveolar crest and an increased thickness in the buccal bone. The canine and
      premolars in this area were expanded buccally by more than 3 mm, and yet there
      had actually been an increase in the buccolingual thickness of the overlying
      buccal bone. Additionally, a preexisting bony fenestration buccal of the root of
      the first premolar was covered. Both of these findings lend credence to the
      incorporation of the bone augmentation procedure into the corticotomy surgery
      because this made it possible to complete the orthodontic treatment with a more
      intact periodontium. The rapid expansive tooth movements with no significant
      apical root resorption may be attributed to the osteoclastic or catabolic phase
      of the regional acceleratory phenomenon. Instead of bony "block" movement or
      resorption/apposition, the degree of demineralization/remineralization might be a
      more accurate explanation of what occurs in the alveolar bone during physiologic
      tooth movement in these patients.

PMID- 11829042
TI  - The influence of patients' concerns on surgeons' recommendations for early breast
      cancer.
AB  - This paper examines whether an older patient's concerns about surgical treatment
      of breast cancer--such as fear of dying or about losing a breast--affect the
      treatment recommendations by their surgeons. A sample of 137 older women
      diagnosed with early stage breast cancer between 1994 and 1996 were interviewed
      within 2 months of diagnosis to determine demographic characteristics, their
      attitudes about breast cancer treatments, and which surgical treatment their
      surgeon initially recommended. The treatment preferences of the 35 surgeons
      treating these women were ascertained by asking them what treatment they would
      usually recommend to a hypothetical 75-year-old woman with early stage breast
      cancer. Patients who reported their feelings about losing a breast as 'very
      important' were less likely to be recommended mastectomy (Odds Ratio (OR) = 0.39;
      95% (Confidence Interval) CI 0.16, 0.94), while patients who reported fear of
      dying from breast cancer as 'very important' were more likely to be recommended
      mastectomy (OR = 4.60; 95% CI 1.94, 11.59), after adjusting for surgeons' age and
      the surgeons' treatment preference when presented with a hypothetical patient. It
      is concluded that surgeons integrate patients' attitudes and concerns into their
      treatment recommendations.

PMID- 11829043
TI  - A pilot study on the effect of progressive muscle relaxation training of patients
      after stoma surgery.
AB  - Eighteen patients who had undergone stoma surgery were assessed with respect to
      their anxiety level and self-reported quality of life (QoL) on three occasions;
      namely, immediately after surgery, 5 weeks after surgery, and 10 weeks after
      surgery. The patients were randomised into a control group (n = 10) and an
      experimental group (n = 8). A 20-min set of audiotaped instructions on
      progressive muscle relaxation training (PMRT) was given to the patients in the
      experimental group for home practice. Assessment instructions included the
      Chinese State-Trait Anxiety Inventory (C-STAI), the Quality of Life Index for
      Colostomy (QoL-Colostomy) and the Hong Kong Chinese version of the World Health
      Organisation Quality of Life Scale (WHOQoL). Results indicated that there was a
      significant decrease in both the C-STAI score (F = 4.66, P < 0.05) and the WHOQoL
      score (F = 4.74, P < 0.05) in the experimental group. Among the domains of
      WHOQoL, a significant difference was shown in physical health/independence and
      general perception of QoL, with the experimental group demonstrating better
      functioning. For the QoL-Colostomy, however, there was no significant difference
      between the control and experimental groups. The results suggest that the use of
      PMRT could enhance quality of life and decrease state anxiety in patients after
      stoma surgery.

PMID- 11829044
TI  - Evaluation of the chemotherapy patient monitor: an interactive tool for
      facilitating communication between patients and oncologists during the cancer
      consultation.
AB  - Effective communication between oncologists and patients with cancer is of
      paramount importance. The Chemotherapy Patient Monitor (CPM) is a novel tool
      designed to assist doctor-patient communication regarding patient concerns and
      side-effects. Initially, the CPM was assessed in a primary evaluation study of
      its use during consultations with 26 patients with advanced colorectal cancer
      (one consultation without, followed by two with, the CPM per patient). This led
      to a further dissemination/audit of 34 patients attending oncology centres in the
      UK, who had completed the survey prior to three consultations. The CPM contains a
      checklist of common side-effects of chemotherapy regimens used in advanced
      colorectal cancer, and other common concerns of patients with advanced colorectal
      cancer. The CPM records the presence of side-effects/concerns, the distress
      caused, whether patients wish to discuss them further, and actions taken as a
      result. Questionnaires explored the views of patients and oncologists in the UK
      and Spain regarding the effectiveness of consultations during a baseline visit
      conducted without the CPM, and then with the CPM in subsequent visits. These data
      were then complemented by the dissemination/audit study of the CPM across nine
      centres in the UK. All patients understood the CPM. The CPM was rated as useful
      by oncologists in 83% of consultations, and did not lengthen 82% of visits.
      Patients felt it had improved the visit in 95% of cases. Responses from patients
      (100%) and oncologists (84%) indicated willingness to use the CPM for at least
      some consultations in the future. The results of the dissemination/audit study
      supported these conclusions. We conclude that the CPM appears to be a useful new
      tool for improving patient-doctor communication during cancer consultations.

PMID- 11829047
TI  - New challenges in cancer treatment and care.

PMID- 11829046
TI  - Forum for applied cancer education and training.

PMID- 11829045
TI  - Health-related quality of life, symptom distress and sense of coherence in adult
      survivors of allogeneic stem-cell transplantation.
AB  - This is the first Swedish study to evaluate the health-related quality of life
      and sense of coherence in adult survivors of allogeneic, haematopoietic stem cell
      transplantation (HSCT). Twenty-five recipients completed three questionnaires 2-4
      years after the transplantation. The questionnaires used were the Sickness Impact
      Profile (SIP), the Symptom Frequency Intensity and Distress (SFID-BMT) scale and
      the Sense of Coherence (SOC) scale measuring subjective functional status,
      symptom distress and coping ability. Impairments in functional status were found,
      as compared with a population norm. The most common impairments were found in the
      areas of social interaction and sleep and rest. Eye problems, dry mouth, cough,
      sexual problems, tiredness, anxiety and changes of taste were symptoms reported
      by more than half of the patients. Despite impaired functioning and a high
      incidence of symptoms, the general health was described as quite good or
      excellent by 80% (n = 20) of the patients. The majority (20/22) had also been
      able to return to work or to attend school. No difference in the sense of
      coherence was seen, as compared with the population norm. Functional impairments
      were significantly correlated to a lower degree of sense of coherence.

PMID- 11829048
TI  - Freedom from pain.

PMID- 11829049
TI  - Calcium and prostate cancer.

PMID- 11829050
TI  - Caelyx and ovarian cancer.

PMID- 11829051
TI  - New drug for prostate cancer.

PMID- 11829052
TI  - Pain management of the future.

PMID- 11829053
TI  - Evaluating the effectiveness of advocacy training for breast cancer advocates in
      Australia.
AB  - There is growing trend in health care for patients and consumers to have an
      active voice in all decisions related to their care. The purpose of the current
      study was to assess the effectiveness of an advocacy training programme for
      breast cancer consumers in Australia. The participants included 51 women who
      attended a 3-day advocacy training programme in three different states across
      Australia. Participants completed a pre- and post-questionnaire at 6 months
      follow-up to assess their involvement in breast cancer advocacy activities and
      organizations. Findings revealed a significant increase in participants'
      involvement in serving as a member of a board or committee, working on clinical
      trials recruitment issues, working on patient resources, and involvement in
      breast cancer advocacy groups after completing the training programme. However,
      no change was found in other key advocacy areas, such as, lobbying for change or
      reviewing research protocols. Implications for future advocacy training
      programmes and research were discussed.

PMID- 11829054
TI  - The carer's place in the cancer situation: where does the carer stand in the
      medical setting?
AB  - Recent thinking about policy on cancer services in the UK has highlighted the
      importance of recognising the needs of carers, but is unclear about the ways in
      which this might be done. Our recent study on the psychosocial needs of cancer
      patients and their main informal carers was unusual in its combined focus on
      patients and carers experiencing the 'cancer journey' together. One of our aims
      was to contribute to an understanding of what it means to be the main carer of
      someone with cancer. Using the qualitative data from the 79 carers and patients
      we interviewed, we ask how carers negotiate their place in the cancer situation,
      and particularly how do carers identify their role in relation to the patient and
      the medical setting? We posit carers as taking part in a shifting process of
      'carerhood' in which competing needs vie for space. Our evidence suggests carers
      actively negotiate the challenges of their position in dealing with issues of
      identity, support, and sharing. We suggest that when the carer's involvement in
      the cancer scenario is recognised and legitimised by others it is easier for them
      to attend to their own needs alongside those of the patient.

PMID- 11829055
TI  - Psychosocial dimensions of BRCA testing: an overshadowed issue.
AB  - Routine cancer susceptibility testing will soon be feasible in clinical practice.
      However, to date, this new technology has entailed many limitations, including
      potential adverse psychosocial consequences. Empirical studies examining these
      psychosocial aspects are strikingly scarce, especially in continental European
      countries. Are we prepared for managing the psychosocial problems that emerge
      from widespread introduction of this practice? Current research do not take into
      account cross-cultural variations in attitudes and reactions towards genetic
      testing. This paper points to the urgent need for obtaining a more accurate
      picture on the psychosocial aspects of breast cancer gene testing and disclosure
      in order to design recommendations for implementation in populations with highly
      variable cultural and legal background.

PMID- 11829056
TI  - Actions of Androctonus australis and Leiurus quinquestriatus venoms in the rat
      isolated atria and anesthetized rats; effect of magnesium and lidocaine.
AB  - In rat isolated atria, Androctonus australis (Aa), Leiurus quinquestriatus
      quinquestriatus (Lqq), and L. q. hebraceus (Lqh) venoms produced intense
      contracture, alterations in the force and frequency of the spontaneous atrial
      contractions, and delayed afterdepolarizations (DAD). It was shown by means of
      tetrodotoxin-induced blockade of neurotransmitter release that the contracture
      and DAD were produced by the action of the venoms on the atrial cell membrane
      (direct action) while alterations in the force and frequency of the spontaneous
      atrial contractions were caused by acetylcholine and norepinephrine released by
      the venoms (indirect action). The irregularities in the spontaneous contractions
      and DAD were suppressed by magnesium and lidocaine which, however, caused only a
      small reduction in the intensity of the atrial contracture. The venom-induced DAD
      was also abolished by ryanodine and intensified by an increase in [Ca2+]0. In
      anesthetized rats, Aa, Lqq, and Lqh venoms induced hypertension, arrhythmias, and
      T wave inversion. The arrhythmias included bradycardia, ventricular and
      supraventricular extrasystoles, unsustained and sustained ventricular tachycardia
      with torsade de pointes episodes. Magnesium and lidocaine abolished them, and
      magnesium also counteracted the hypertension. These results suggest that
      magnesium and lidocaine, particularly magnesium, may be useful in the treatment
      of the arrhythmias, hypertension, and other disorders associated with Buthinae
      scorpion envenomation.

PMID- 11829057
TI  - Pharmacology and chemistry of the venoms of solitary wasps.
AB  - In this study certain activities of solitary wasp venoms collected from the Suez
      Canal area (Bembix oculata, Dielis collaris, and Scolia erythrocephala) were
      investigated. The effects of these venoms on different types of muscles were
      studied, and in addition, the chemical structures were studied by electrophoretic
      analysis. We found that the venoms affect different types of muscles (cardiac,
      skeletal, and smooth) in different ways. The effect of the venoms on heart muscle
      was rapid and led to bradycardia, an increase in R amplitude on ECG, and other
      cardiac disorders such as atrioventricular block. These effects were abolished by
      atropine, indicating they were mediated through the peripheral nervous system.
      All of the venoms we tested reversibly blocked the nicotinic receptors of toad
      skeletal muscle and the muscarinic receptors of smooth muscles. Through
      electrophoretic analysis, seven bands were detected in Dielis collaris venom,
      while five bands were detected in Bembix oculata venom.

PMID- 11829058
TI  - Biochemical and biological properties of Trimeresurus jerdonii venom and
      characterization of a platelet aggregation-inhibiting acidic phospholipase A2.
AB  - Several biochemical and biological activities such as phospholipase A2, arginine
      esterase, proteolytic, L-amino acid oxidase, 5'nucleotidase,
      acetylcholinesterase, thrombin-like, anticoagulant, and hemorrhagic activities
      were determined for whole desiccated venom of Trimeresurus jerdonii. An acidic
      phospholipase (named TJ-PLA2) was purified by anionic exchange chromatography,
      gel filtration, and reverse phase HPLC. TJ-PLA2 had a molecular weight of 16,000
      and a pI of 4.8. TJ-PLA2 was non-lethal to mice up to an i.p. dose of 15 mg/kg
      body weight and lacked neurotoxicity and myotoxicity. It induced edema in the
      footpads of mice. The purified enzyme inhibited ADP- and collagen-induced human
      platelet aggregation in a manner which was both dose- and time-dependent.

PMID- 11829059
TI  - The purification and N-terminal sequencing of a polypeptide that prolongs action
      potentials by altering Na channel inactivation from the venom of Buthus martensii
      Karsch.
AB  - A polypeptide that extensively prolongs action potentials (APs) in frog nerve has
      been isolated and purified from the venom of the scorpion Buthus martensii Karsch
      (BMK). The polypeptide was purified using gel filtration, ion exchange, FPLC, and
      HPLC chromatography. APs recorded in the presence of nanomolar concentrations of
      the polypeptide were extensively prolonged without much attenuation in their
      heights. The N-terminal sequence of BMK 11(2) was found to be: VRDGYIADDKD-AYF
      GRDAYYDDDEKKKD. Sequence similarity comparisons to other alpha-scorpion toxins
      suggest that the two blanks in the sequences are cysteines. The molecular weight
      (M.W.) of BMK 11(2) was determined by LC/MS/MS to be 7216 Da. Voltage-clamp
      experiments conducted on plasmid-transfected human kidney cells expressing the
      alpha and beta subunits of the rat sodium channel showed that BMK 11(2) acted to
      prolong Na channel inactivation. Also, in the presence of 100-200 nM BMK 11(2), a
      persistent non-activating Na current was induced when the membrane was
      depolarized from a -120 mV holding potential. BMK 11(2) caused Na channel fast
      inactivation to be further slowed when the holding potential was increased,
      suggesting that BMK 11(2) effects are voltage dependent. Na channel slow
      inactivation and return from slow inactivation were unaffected by the presence of
      BMK 11(2). Since the polypeptide prolongs APs when both K+ and Ca+ channels were
      blocked and shows sequence similarity to other alpha-neurotoxins, it appears
      likely that BMK 11(2) acts to selectively alter Na channel inactivation to
      produce its effect.

PMID- 11829060
TI  - Isolation and characterization of Clostridium botulinum type E from soil of
      Gwalior, India.
AB  - A strain of Clostridium botulinum type E has been isolated from soil samples of
      Gwalior, India. The isolated strain shows curved vegetative cells with oval,
      bulging, and terminal spores. The production of toxin was detected by
      immunodiffusion test, symptomatic death of mice and mouse protection assay with
      trivalent antitoxin (A+B+E). The culture supernatant gave 10(3) MLD (minimum
      lethal dose) per ml without any protease treatment. Group specific and serotype
      specific primers amplified the DNA fragments of 260 bp and 445 bp, respectively,
      indicating Clostridium botulinum type 'E.'

PMID- 11829061
TI  - Antigenic cross-reactivity of nerve growth factors from diverse source: activity
      versus toxicity of NGF.
AB  - NGF used in these studies was from various sources: cobra venom (V-NGF), mouse
      submaxillary glands (M-NGF), honeybee venom (B-NGF), human serum (H-NGF), and
      cobra serum (CS-NGF). This investigation reports the antigenic cross-reactivity
      of NGFs from the above mentioned diverse sources. Antigenic cross-reactivity of
      NGFs was determined by immunological test, using anti-NGFs against V-NGF, M-NGF,
      B-NGF, and H-NGF. Results revealed that NGF was a conserved protein showing
      antigenic cross-reactivity among the NGFs from diverse source, except for NGFs
      from cobra and bee venoms. Anti B-NGF reacted poorly with cobra venom V-NGF and
      vice versa. Anti M-NGF showed higher antigenic reactivity with human serum H-NGF
      than with honeybee B-NGF and cobra serum CS-NGF. This research also reports that
      the toxicity of NGF is directly related to the biological activity of producing
      neurite outgrowth on PC12 cells. Cobra venom NGF produced neurites at 1-5 ng, and
      it was toxic at 10-20 ng on PC12 cells. After reducing the activity of NGF, it
      was found to be non-toxic to PC12 cells at 50 X concentration.

PMID- 11829063
TI  - 'Interim controls' on movement of livestock.

PMID- 11829062
TI  - Detection of tetrodotoxin by HPLC in shellfishes and goby from south Taiwan.
AB  - High performance liquid chromatography (HPLC) using fluorescent detection
      following post-column alkaline degradation and a sample preparation procedure for
      the analysis were established to detect tetrodotoxins (TTXs) in seafood. In south
      Taiwan Prefectures, each specimen of shellfishes and gobies, collected from
      Chiayi, Tainan, and Pingtung from January 1997 to May 1998, was analyzed by HPLC
      to detect the presence and quantity of TTXs. Overall results showed that only 5
      specimens out of 557 specimens contained TTXs; the toxic species were gastropod
      Natica lineata and Nassarius livescens. The highest TTX content is 10.0 microg/g
      in N. livescens. Gobies and other species of shellfishes were nontoxic. Although
      the rate of toxic specimens in all samples was low and showed no seasonal trends,
      the TTX contents of toxic specimens were higher than safety criteria value.

PMID- 11829065
TI  - Clinical findings and treatment of listeriosis in 67 sheep and goats.
AB  - This paper describes the clinical findings and treatment of 67 sheep and goats
      with listeriosis. In 55 of them the diagnosis was made on the basis of the
      typical signs, which included vestibular ataxia, circling, head tilt and
      unilateral cranial nerve deficits, but in 12 animals a definitive diagnosis was
      made only after postmortem examination. The most significant haematological and
      biochemical findings were a high haematocrit in 16 animals, a high concentration
      of total protein in 33, a high concentration of bilirubin in 39 and a high
      concentration of urea nitrogen in 28 animals. Twenty-eight of the animals had a
      metabolic acidosis. Thirty-nine animals were treated with antibiotics,
      intravenous sodium chloride and glucose solutions and sodium bicarbonate. Ten of
      them survived and the others were euthanased because their condition
      deteriorated. Of the 10 that survived, nine were able to stand when they were
      first examined and one was in lateral recumbency. Of 15 animals treated with
      chloramphenicol, one survived; of 11 animals treated with oxytetracycline, two
      survived; and of nine animals treated with gentamicin and ampicillin, six
      survived.

PMID- 11829064
TI  - Genotypic prevalence of the fimbrial adhesins (F4, F5, F6, F41 and F18) and
      toxins (LT, STa, STb and STx2e) in Escherichia coli isolated from postweaning
      pigs with diarrhoea or oedema disease in Korea.
AB  - A PCR was used to determine the genotypic prevalence of five fimbrial adhesins
      (F4, F5, F6, F41 and F18), two heat-stable enterotoxins (STa and STb), the heat
      labile enterotoxin (LT), and the shiga toxin 2e (Stx2e) in 230 isolates of
      Escherichia coli from postweaning pigs with diarrhoea or oedema disease. Ninety
      four (40.9 per cent) of the isolates carried genes for at least one of the
      fimbrial adhesins or toxins. Genes for the F18 fimbrial adhesin were detected in
      18.3 per cent, and genes for F4, F6, F5 and F41 were detected in 10.0 per cent,
      4.3 per cent, 1.7 per cent and 0.8 per cent of the isolates, respectively. Genes
      for STa, STb and LT were detected in 25.7 per cent, 15.2 per cent and 8.7 per
      cent of the isolates, respectively. Genes for Stx2e were detected in 36 (15.6 per
      cent) of the isolates, and among them 24 also contained the gene for F18ab and
      four also contained the gene for F18ac.

PMID- 11829066
TI  - Collagenous and elastic system fibres in the aorta of cattle poisoned by Solanum
      glaucophyllum.
AB  - The proportions of fibres of the collagenous and elastic systems were measured in
      the aortas of three normal heifers and in nine heifers given the calcinogenic
      plant Solanum glaucophyllum for 15, 30 or 60 days. There were decreases in the
      amount of collagen relative to reticulin, and in the proportion of elastic fibres
      which were related to the period of dosing. These changes may have an adverse
      influence on the animals' cardiovascular function.

PMID- 11829067
TI  - Effective treatment of severe facial dermatitis in lambs.

PMID- 11829068
TI  - Cerebral taeniid oncospheral lesions in two BSE suspects.

PMID- 11829069
TI  - Thiazole orange-positive platelets in a dog with idiopathic thrombocytopenic
      purpura.

PMID- 11829070
TI  - Head height requirements, and assessing stocking density, for sheep in transit.

PMID- 11829071
TI  - Retrospective investigation of feline cowpox in Germany.

PMID- 11829072
TI  - National Scrapie Plan.

PMID- 11829073
TI  - Early socialisation of puppies.

PMID- 11829074
TI  - Early socialisation of puppies.

PMID- 11829075
TI  - In-house diagnostic test kits.

PMID- 11829076
TI  - Cannabis ingestion in a chinchilla.

PMID- 11829077
TI  - Release into the wild of grey squirrels.

PMID- 11829078
TI  - Uterine torsion in twin pregnancies in dairy cattle.

PMID- 11829079
TI  - Mechanisms of bone remodeling: implications for clinical practice.
AB  - The adult skeleton undergoes continuous remodeling. The remodeling cycle involves
      the interaction of cells of osteoblastic and osteoclastic lineage and is
      regulated by both systemic hormones and local factors. In addition to the
      systemic calcium-regulating hormones, parathyroid hormone, 1,25-dihydroxy vitamin
      D and calcitonin, sex hormones play an important role. Estrogen has been
      identified as the major inhibitor of bone resorption in both men and women.
      Androgen is important not only as a source of estrogen, through the action of
      aromatase, but also for its direct effect in stimulating bone formation. The
      effects of sex hormones may be mediated by their ability to alter the secretion
      of local cytokines, prostaglandins and growth factors. Sex hormone action is also
      modulated by the level of sex hormone-binding globulin in the circulation. A more
      precise analysis of these effects has been made possible by the development of
      new methods of measuring not only bone mineral density, but also relative rates
      of bone formation and resorption using biochemical markers. These new approaches
      have allowed us to define more precisely the specific roles of androgens,
      estrogens and other regulatory hormones in human skeletal physiology and
      pathophysiology.

PMID- 11829080
TI  - Overview of bone mineral density in postmenopausal women.
AB  - The risk of osteoporosis is directly related to factors that influence bone
      remodeling premenopausally and postmenopausally. Some of these factors are
      nonmodifiable--for example, race and the genetic control of osteogenesis. Other
      factors, such as lifestyle, exercise and nutrition, can be influenced to enhance
      bone mineral accrual and thereby lessen the risk of or even prevent osteoporosis.
      Central to the health of the bone-remodeling cycle is the role of the sex
      steroids estrogen and androgen, and their bioavailability to estrogen and
      androgen receptors in the osteoclasts, osteoblasts and osteocytes. Apart from
      their direct action on bone cells, sex steroids modulate the bone-preserving
      function of modifiable factors. The efficacy of sex steroids is proportional to
      their bioavailability in the "free" form. This is equally true of endogenously
      synthesized hormones and of hormone replacement therapy.

PMID- 11829081
TI  - Therapies to improve bone mineral density and reduce the risk of fracture:
      clinical trial results.
AB  - Osteoporosis is a skeletal disorder that is associated with lowered bone mineral
      density and increased risk of fracture. Numerous clinical trials have been
      conducted to study drugs and lifestyle changes that can either prevent bone loss
      in perimenopausal women or prevent fractures in women with established
      osteoporosis. The role of estrogen alone or in combination with androgen as
      hormone replacement therapy is discussed for its potential value in osteoporosis
      prevention and treatment. Additional therapies that are examined for prevention
      and treatment of osteoporosis include tibolone, bisphosphonates (alendronate and
      risedronate), selective estrogen-receptor modulators, calcitonin and parathyroid
      hormone. Experimental therapies that are in different phases of evaluation in
      osteoporosis management include statins as well as tumor necrosis factor-receptor
      antagonists. Other strategies include nonpharmacologic interventions, such as
      calcium supplements, vitamin D and exercise.

PMID- 11829082
TI  - Increased frequency dependence of specific airway resistance in patients with
      laryngeal hemiplegia.
AB  - The aim of this study was to investigate whether patients with laryngeal
      hemiplegia (LH) show a frequency-dependent increase in specific airway resistance
      (sRaw), measured by body plethysmography. In addition to the flow-volume loop,
      usually considered in the functional evaluation of upper airway obstructions,
      variations in sRaw at respiratory frequencies of 30+/-5 (=0.5 Hz), 60+/-5 (=1 Hz)
      and 90+5 breaths x min(-1) (=1.5 Hz) in 21 never-smoking patients (LH group, mean
      age+/-SD 55+/-12.09 yrs; 17 females) whose unilateral vocal-cord paralysis was
      documented by laryngoscopy and who had no signs or symptoms of other respiratory
      diseases studied. They were compared to 21 healthy control subjects (C group:
      50.1+/-15.44 yrs; 10 females). The sRaw values at 30+/-5 breaths min(-1) were
      similar in the two groups (5.54+/-1.88 versus 5.68+/-1.06 cmH2O x s(-1); p=NS),
      but at increasing frequencies (30+/-5, 60+/-5 and 90+/-5 breaths min(-1)), they
      progressively and significantly increased in the LH patients (from 5.54+/-1.88 to
      6.63+/-1.96 and 8.05+/-2.6 mH2O x s(-1); p<0.0005), and not significantly in
      controls (5.68+/-1.06, 5.85+/-0.95 and 5.9+/-1.12 cmH2O x s(-1); p=NS). Linear
      discriminant analysis using AsRaw (sRaw at 1.5 Hz-sRaw at 0.5 Hz) and forced
      inspiratory flow at 50% of the vital capacity made it possible to correctly
      classify all of the controls and 19 of the 21 patients. In conclusion, the
      multiple, rapid and noninvasive plethysmographical testing of frequency-dependent
      increase in specific airway resistance with the flow-volume loop, allows the
      sufficiently satisfactory discrimination of laryngeal hemiplegia patients from
      controls.

PMID- 11829083
TI  - The repeatability of nonbronchoscopic bronchoalveolar lavage differential cell
      counts.
AB  - Airway inflammation in children can be assessed by nonbronchoscopic
      bronchoalveolar lavage (BAL). Little is known about the repeatability of cell
      counts in the BAL obtained. Children (n=43) attending for elective surgery were
      studied. Cell counts were obtained following a nonbronchoscopic lavage. Two
      samples were obtained with either: 1) the catheter wedged in the same position
      (n=21) or 2) the catheter reinserted and wedged again (n=22). Slides (n=30) from
      nonbronchoscopic lavage samples were selected at random and two independent
      observers counted 500 cells on each slide on two occasions. The repeatability of
      the lavage sampling and cell counting was assessed for different cell types. The
      inter- and intra-observer repeatability for the differential cell counting
      demonstrated that there was good repeatability for all cell types except
      lymphocytes (interobserver: Lin's concordance coefficient 0.42; repeatability
      coefficient 0.66). Quantification of eosinophil (%) was highly repeatable using
      either method (Lin's concordance coefficient 1) 0.99, 2) 0.95; repeatability
      coefficient 1) 0.58, 2) 1.36). Nonbronchoscopic lavage is a repeatable technique
      for the quantification of eosinophils. Variation in the sampling method can be
      reduced by taking two separate samples and averaging the differential cell
      counts. Furthermore, increasing the number of cells counted should ensure
      accurate quantification of lymphocytes.

PMID- 11829084
TI  - The immunology of virus infection in asthma.
AB  - The respiratory tract is commonly infected by a range of viruses with overlapping
      pathologies. The majority of episodic exacerbations of asthma are associated with
      viral infection, in particular with rhinovirus infections. Experimental
      rhinovirus infection in human volunteers provides a useful model of natural virus
      induced asthma. The asthmatic airway is characterized by an infiltrate of
      eosinophils and T-lymphocytes expressing the type 2 cytokines interleukin (IL)-4,
      IL-5 and IL-13. An effective antiviral immune response requires early viral
      clearance and appropriate termination of the immune response to minimize
      associated immunopathology and tissue damage. The antiviral immune response is
      made up of innate (nonspecific) and specific components, and requires the
      coordinated actions of many different cell types including neutrophils,
      macrophages, eosinophils, dendritic cells, epithelial cells, mast cells, natural
      killer cells and B- and T-lymphocytes. Coordination of this response involves
      numerous cytokines and chemokines. T-lymphocytes expressing type 1 cytokines
      including interferon-gamma play a key role. Pre-existing asthmatic inflammation
      in the lower airway may modify the immune response to viral infection by altering
      the balance of T-cell cytokine expression from type 1 towards a type 2 in what is
      always a mixed response. The consequence is delayed viral clearance, persistent
      virus-induced inflammation and amplification of the allergic inflammation.

PMID- 11829085
TI  - Chemotherapy in small cell lung cancer.
AB  - Chemotherapy is the backbone in the treatment of small cell lung cancer (SCLC)
      and radiotherapy is an important adjunct in limited stage disease. The role of
      chest irradiation is now documented in three meta-analysis, based on the same
      body of data. Trials on timing, scheduling and fractionation could have followed
      a more stringent development line but altogether, the highest efficacy seems to
      be obtained with early, concurrent twice-daily chest irradiation. Patients in
      complete remission should have prophylactic cranial irradiation, which reduces
      the risk of brain metastases and of death from SCLC. Four series of chemotherapy
      seem to be sufficient in limited-stage disease while six is recommended in
      extensive disease. The combination of etoposide plus cis- or carboplatin is
      appropriate in both stages and addition of other agents has no clinically
      important impact on the survival. Use of haematological growth factors such as
      granulocyte colony stimulating factor (G-CSF) and granulocyte macrophage colony
      stimulating factor (GM-CSF) may enable higher doses or more frequent dosage.
      Three randomized trials on GM-CSF showed a negative outcome while G-CSF support
      may result in better survival rates, but a more cost-efficient policy must be
      found. High-dose chemotherapy plus haematological stem-cell support is still
      under investigation but disappointing long-term survival rates means there is not
      much optimism for this strategy. New strategies in general are requested in the
      treatment of extensive-stage disease and of elderly patients. Phase II trials
      suggest that good-risk patients with extensive disease should be treated
      aggressively, intermediate-risk patients more gently, and palliation must be the
      primary aim in the treatment of poor-risk patients. In elderly patients
      impressive survival rates are obtained with 3-4 series of chemotherapy and
      radiation delivered in 5-10 fractions. A number of new agents are active but more
      trials are required before each has found a place, if any, in the treatment of
      small cell lung cancer. To conclude, the randomized trial is still an important
      instrument in clinical oncology, and trials in small cell lung cancer must be
      large, which is why the cooperation of organizations and multicentres is urgent.

PMID- 11829086
TI  - Relationship between respiratory syncytial virus bronchiolitis and future
      obstructive airway diseases.
AB  - Evidence from a large number of prospective case-control studies shows that
      respiratory syncytial virus (RSV) bronchiolitis in infancy is often associated
      with recurrent wheezing and asthma during subsequent years. However, wheezing
      tends to diminish and most studies show no significant increase in wheezing
      compared to controls by school age or adolescence. An unresolved question is
      whether severe RSV infection during infancy causes the respiratory sequelae or
      inherent abnormalities predispose an infant to develop severe respiratory
      infection and sequelae, i.e. RSV is associated with the development of pulmonary
      sequelae. Studies on long-term outcome of RSV bronchiolitis are reviewed from an
      evidence-based perspective. The majority of prospective placebo-controlled
      studies do not show any long-term beneficial effects of corticosteroid treatment,
      i.e. the risk of subsequent wheezing is not diminished by the treatment. The
      evidence for an increased risk of allergic sensitization after RSV bronchiolitis
      is not nearly as strong as the evidence for an increased risk of subsequent
      wheezing. In fact, most studies do not show any significant increase in atopy
      after RSV bronchiolitis. This suggests that the increased risk of wheezing after
      RSV is not linked to an increased risk of atopy. There are some indications that
      infants who develop severe RSV and subsequent wheezing may have aberrations that
      predate the RSV infection. To decide whether respiratory syncytial virus
      bronchiolitis causes, or is associated with the respiratory sequelae (or with
      subsequent allergy), it will be necessary to conduct prospective, randomized
      studies, where the cytokine profile prior to bronchiolitis onset is known. Such
      studies should preferably include some form of intervention against respiratory
      syncytial virus. A more complete understanding of the risk factors for severe
      respiratory syncytial virus infection and the role of respiratory syncytial virus
      infection in the initiation of asthma is needed as a basis for large-scale and
      cost-effective programmes to prevent respiratory syncytial virus-related
      morbidity.

PMID- 11829087
TI  - The new World Health Organization classification of lung tumours.
AB  - Tumour classification systems provide the foundation for tumour diagnosis and
      patient therapy and a critical basis for epidemiological and clinical studies.
      This updated classification was developed with the aim to adhere to the
      principles of reproducibility, clinical significance, and simplicity in order to
      minimize the number of unclassifiable lesions. Major changes in the revised
      classification as compared to the previous one (WHO 1981) include the addition of
      two pre-invasive lesions to squamous dysplasia and carcinoma in situ; atypical
      adenomatous hyperplasia and diffuse idiopathic pulmonary neuroendocrine cell
      hyperplasia. Another change is the subclassification of adenocarcinoma: the
      definition of bronchioalveolar carcinoma has been restricted to noninvasive
      tumours. There has been substantial evolution of concepts in neuroendocrine lung
      tumour classification. Large cell neuroendocrine carcinoma (LCNEC) is now
      recognized as a histologically high grade non small cell carcinoma showing
      histopathological features of neuroendocrine differentiation as well as
      immunohistochemical neuroendocrine markers. The large cell carcinoma class has
      been enriched with several variants, including the LCNEC and the basaloid
      carcinoma, both with a dismal prognosis. Finally, a new class was defined called
      carcinoma with pleomorphic, sarcomatoid, or sarcomatous elements, which brings
      together a number of proliferations characterized by a spectrum of epithelial to
      mesenchymal differentiation. Immunohistochemistry and electron microscopy are
      invaluable techniques for diagnosis and subclassification, but our intention was
      to render the classification simple and practical to every surgical laboratory,
      so that most lung tumours could be classified by light microscopic criteria.

PMID- 11829088
TI  - A female with cough, dyspnoea and chest pain.

PMID- 11829089
TI  - A patient with fever, haemoptysis, and tenderness of calf muscles.

PMID- 11829090
TI  - Daily respiratory mortality and PM10 pollution in Mexico City.

PMID- 11829091
TI  - Angiotensin converting enzyme in patients with sleep apnoea syndrome: plasma
      activity and gene polymorphisms.

PMID- 11829092
TI  - Ventilator-associated pneumonia.

PMID- 11829093
TI  - Global initiative for chronic obstructive lung diseases (GOLD): time to act.

PMID- 11829094
TI  - Guidelines versus clinical practice in the treatment of chronic obstructive
      pulmonary disease.
AB  - The main purpose of this study was to assess whether pharmacological treatments
      prescribed by respiratory physicians to patients with chronic obstructive
      pulmonary disease (COPD) were consistent with the guidelines. The treatments
      prescribed by respiratory physicians to 631 consecutive patients with COPD,
      compared to 879 asthmatics were prospectively recorded. All subjects underwent
      peak expiratory flow rate measurement, spirometry and assessment of recent
      evolution and dyspnoea (visual analogue and Medical Research Council scales).
      Patients with COPD received more treatments than asthmatics (mean+/-SD: 2.6+/-0.5
      versus 2.2+/-0.4, p<0.0001). Treatments administered to patients with COPD were
      beta2-agonists in 78% (versus 94% in asthmatics), anticholinergic agents (AC) in
      56% (versus 16% in asthma), methylxanthines in 31% (versus 15% in asthma) and
      inhaled corticosteroids in 76% (versus 85% in asthma). Intensity of treatment was
      influenced by disease severity for all treatments except AC. In conclusion,
      pharmacological treatment of chronic obstructive pulmonary disease by respiratory
      physicians is only partially consistent with current guidelines, with a high
      proportion of inhaled corticosteroid prescriptions and a relative under-use of
      anticholinergic agents; this most likely reflects the persistent uncertainties of
      physicians, and emphasizes that more efforts are required to improve
      implementation of chronic obstructive pulmonary disease guidelines and assess the
      efficacy and cost-effectiveness of recommended strategies.

PMID- 11829095
TI  - International approaches to the prescription of long-term oxygen therapy.
AB  - While there is broad agreement about who should receive long-term oxygen therapy
      (LTOT), there is little information available on how clinicians should decide on
      the oxygen prescription itself, at rest, during sleep and during exercise. The
      authors describe the results of an international survey that was undertaken to
      compare how respirologists prescribed oxygen. A questionnaire was sent to 100
      respirologists in each of seven countries. The questionnaire identified whether
      resting flow rates were derived in a standard manner or by individualized patient
      testing. Test targets were ascertained for rest, exercise and sleep, as was the
      percentage of time that each test target had to reach for the test to be
      accepted. The majority of respondents individualized the oxygen prescription at
      rest (81%). Resting arterial oxygen saturation (Sa,O2) was most commonly targeted
      at 90-91%. The approach to night prescription varied (p<0.001). Respirologists in
      Canada and the USA increased the resting Sa,O2 by 1-2 L x min(-1) during sleep,
      while those in Spain used the resting (awake) flow for the night prescription
      (62%). Respirologists in the Netherlands, France, and Italy individualized the
      night prescription more frequently. Although oxygen during exercise was
      individualized in most countries (74%), significant differences remained among
      countries (p<0.001). The majority of respirologists (62%) aimed to achieve an
      Sa,O2 of 90-91% during exercise, while 70% of all respirologists tried to achieve
      the desired Sa,O2 for 90% of the test. There were substantial differences among
      countries as to how the oxygen prescription was written. This survey highlights
      the need for multicentre studies that improve the effectiveness of long-term
      oxygen therapy utilization.

PMID- 11829096
TI  - Evaluation of bronchodilator responses in patients with "irreversible" emphysema.
AB  - Given the emerging physiological and clinical rationale for pharmacological lung
      volume reduction, assessment of volume responses to bronchodilators is likely to
      be highly relevant in chronic obstructive pulmonary disease (COPD). The authors
      examined the magnitude of lung-volume reduction after acute bronchodilator
      treatment in patients with advanced emphysema. Eighty-four stable patients with
      emphysema (mean+/-SEM forced expiratory volume in one second (FEV1): 32+/-1%
      predicted) performed spirometry and body plethysmography before and 15-30 min
      after 200 microg salbutamol. Only irreversible patients with a postbronchodilator
      change in FEV1 <10% pred were considered in this study. Postsalbutamol, the
      majority of subjects (83%) had significant improvements in one or more lung
      volumes: on average, residual volume (RV), functional residual capacity (FRC),
      inspiratory capacity (IC), forced vital capacity and slow vital capacity changed
      by -18+/-2, -10+/-1, 8+/-1, 9+/-1 and 7+/-1% pred (p<0.0005 each). Total lung
      capacity (TLC) decreased 0.12+/-0.04 L (p<0.01). Change in IC reflected change in
      FRC (r=-0.60, p<0.0005), but more strongly in the 57% of patients with no
      significant change in TLC (r=-0.93, p<0.0005). The magnitude and frequency of
      volume responses were greatest in patients with the most severe COPD; for
      example, RV decreased by 0.51+/-0.09 L (23+/-4% pred) and 0.27+/-0.04 L (14+/-2%
      pred) in severe and moderate subgroups, respectively. Significant reductions in
      lung hyperinflation occurred in the absence of a change in forced expiratory
      volume in one second after low-dose salbutamol in a majority of patients with
      advanced emphysema; the greatest changes occurred in those with the most severe
      disease.

PMID- 11829097
TI  - Airway responsiveness and peak flow variability in the diagnosis of asthma for
      epidemiological studies.
AB  - Airway responsiveness and variability in peak expiratory flow (PEF) are widely
      used as objective diagnostic measures of asthma, but it is not clear how these
      variables should be calculated or adjusted to obtain the highest diagnostic
      validity for physician-diagnosed asthma in the community. Data from a community
      based sample of 1,513 adults has been used. Airway responsiveness to methacholine
      and 7-day PEF data were obtained in 1991, asthma and respiratory symptoms were
      diagnosed by questionnaires in 1991 and 1999. Airway responsiveness was expressed
      as the provocative dose causing a 20% fall in forced expiratory volume in one
      second (PD20), two-point and least-squares regression slopes. PEF variability was
      expressed as daily amplitude, weekly standard deviation and mean of the two
      lowest readings. Continuous measures were adjusted for measures of baseline
      airway calibre by linear regression. Measures of airway responsiveness had
      greater sensitivity for specificity for self-reported diagnosed asthma than
      expressions of PEF variability, before and after adjustment for airway calibre.
      Diagnostic validity was substantially better in adults aged <50 yrs; PD20
      provided the best sensitivity for specificity (61% for 95% at 8.3 micromol). In
      those aged > or =50 yrs, no measure was closely related to diagnosed asthma. In
      younger age groups, provocative dose causing a 20% fall in forced expiratory
      volume in one second provides a valuable objective measure of asthma for
      epidemiological studies, but is unable to distinguish between asthma and chronic
      obstructive pulmonary disease in older people.

PMID- 11829098
TI  - Safety of formoterol Turbuhaler at cumulative dose of 90 microg in patients with
      acute bronchial obstruction.
AB  - This study compared the safety of formoterol (Oxis Turbuhaler; 90 microg
      delivered dose; 120 microg metered dose) with terbutaline (Bricanyl Turbuhaler;
      10 mg), in patients with acute bronchoconstriction. Forty-eight patients (31
      females) with a mean age of 45 yrs, were randomized into two parallel groups
      (double-blind design). Mean baseline forced expiratory volume in one second
      (FEV1) was 0.98 L (33% of predicted normal). Study drugs were administered on six
      occasions during 3 h (formoterol 4.5 microg or terbutaline 0.5 mg x inhalation(
      1), 20 inhalations). Patients received intravenous prednisolone after 1.5 h and
      oxygen during the first 3 h. Pulse rate, serum potassium, 12-lead
      electrocardiogram (ECG), Holter ECG, arterial blood gases and FEV1 were assessed
      during 12 h after the first dose. Four patients (one formoterol, three
      terbutaline) discontinued. The 12-h mean values of serum potassium decreased from
      4.02 to 3.89 mmol x L(-1) for formoterol and from 4.22 to 3.76 mmol x L(-1) for
      terbutaline. Mean 12-h pulse rate was significantly (p<0.01) higher in the
      terbutaline group (101.7 beats per minute (bpm)) than in the formoterol group
      (93.5 bpm). No individual patient value was considered clinically important or
      alarming. FEV1 improved in both groups but with no statistically significant
      difference between treatments. Oxis Turbuhaler (90 microg) was at least as safe
      and well tolerated as terbutaline (10 mg) [DOSAGE ERROR CORRECTED] in patients
      with acute bronchoconstriction.

PMID- 11829099
TI  - Physiological responses of the airway wall and lung in hyperresponsive pigs.
AB  - Airway hyperresponsiveness (AHR) might be driven by mechanisms inherent to the
      airway wall, and/or by factors arising from outside the airways. A porcine model
      of allergen-induced AHR was utilized to investigate physiological responses in
      intact airways in vitro and their contribution to responsiveness in vivo.
      Responsiveness to acetylcholine (ACh) was measured in eight ovalbumin (OA)
      sensitized/challenged pigs (tests) and eight saline-challenged controls. In vivo
      responsiveness to ACh was determined from pulmonary resistance (RL). In vitro
      responsiveness to ACh was determined from airway pressure in isovolumic bronchial
      segments, after exposure via the adventitial or the luminal surface. Test pigs
      had lung (255+/-26% increase in RL, p<0.0001) and skin responses to OA, and AHR
      to ACh (p<0.0001). In vitro, test bronchi were less sensitive than controls to
      ACh applied to the airway adventitia (negative log of the ACh concentration
      producing half the maximum response (pD2)=4.18 and 4.58 respectively, p<0.01),
      but not the lumen. Test bronchi had an increased amount of smooth muscle
      normalized for airway size versus controls (p<0.05). Maximum responses to lumenal
      ACh in vitro showed a weak positive correlation with maximum changes to ACh in
      vivo (r=0.599, p=0.05). This study concludes that the effect of antigen challenge
      on bronchial responsiveness varies with the route of exposure to acetylcholine.
      In vitro responses to lumenal acetylcholine are increased despite a possible
      reduction in responsiveness of airway smooth muscle. Responsiveness of the
      bronchial wall only partially explains responsiveness of the lungs in vivo.

PMID- 11829100
TI  - Can semi-automated image cytometry on induced sputum become a screening tool for
      lung cancer? Evaluation of quantitative semi-automated sputum cytometry on radon-
      and uranium-exposed workers.
AB  - The correlations between semi-automated sputum cytometry (ASC), conventional
      cytology and the final diagnosis was investigated in industrially-exposed
      workers. Slides of sputum samples from 201 former uranium miners with silicosis,
      100 patients with asbestosis, 103 workers resected for lung cancer, and 200
      controls (50% smokers), were stained using the Papanicolaou (Pap) method and the
      Feulgen reaction with thionin. Cytometry was performed using the Cyto-Savant
      automated system. Atypical nuclei were found in 72 of 404 patient samples, 327
      samples were normal and five were inadequate for ASC analysis. Thirteen tumours
      (Pap IV, Pap V) and 11 cases of severe dysplasia were identified by cytology.
      Lung cancer was confirmed in 20 patients. Compared to the final diagnosis of lung
      cancer, the sensitivity of ASC was 75% (15 out of 20) and specificity 89.8% (520
      out of 579). The results represent a diagnostic efficiency of 89.3%. The
      combination of ASC with cytology increased sensitivity to 80% (16 out of 20)
      without significant loss of specificity (89.7% or 523 out of 581). In this
      investigation of a limited number of patients with occupational radon or asbestos
      exposure, semi-automated sputum cytometry appears to be sensitive and reliable
      for the detection of malignant changes in the tracheobronchial mucosa. Together
      with conventional cytology, it would be reasonable to test the validity of the
      combined methods in a large-scale feasibility study of early lung cancer
      detection.

PMID- 11829101
TI  - Changes in pro-inflammatory cytokines in association with exposure to moisture
      damaged building microbes.
AB  - Several epidemiological studies have described an association between adverse
      health effects and exposure to mould and microbes present in the indoor air of
      moisture-damaged buildings. However, the biochemical linkage between microbial
      exposure and the large variety of reported respiratory symptoms is poorly
      understood. In the present study, the authors compared the respiratory symptoms,
      the production of inflammatory mediators interleukin (IL)-1, IL-4, IL-6, tumour
      necrosis factor-alpha (TNF-alpha) and cell count in nasal lavage fluid and
      induced sputum samples of subjects working in moisture-damaged and control school
      buildings. The sampling was performed and the questionnaires were completed at
      the end of the spring term, at the end of the summer vacation (2.5 months),
      during the winter term and after a 1-week winter holiday. The authors found a
      significant elevation of IL-1, TNF-alpha and IL-6 in nasal lavage fluid and IL-6
      in induced sputum during the spring term in the subjects from the moisture
      damaged school building compared to the subjects from the control building. The
      exposed workers reported sore throat, phlegm, eye irritation, rhinitis, nasal
      obstruction and cough in parallel with these findings. The present data suggests
      an association between microbial exposure, and symptoms as well as changes in pro
      inflammatory mediators detected from both the upper and lower airways.

PMID- 11829102
TI  - A case-control study of lifestyle risk factors associated with tuberculosis in
      Liverpool, North-West England.
AB  - The aim of this study was to identify the subtle influences of exposure and
      individual lifestyles on the risk of developing tuberculosis. A retrospective
      case-control study (with matching by sex, age, postcode and ethnicity) of all
      tuberculosis cases notified over a 7-yr period in Liverpool, UK, was carried out.
      Multiple logistic regression showed that, before diagnosis, cases were 7.4 times
      more likely to have had visitors from abroad; 4.0 times more likely to have been
      born abroad; and 3.8 times more likely to have lived with someone with
      tuberculosis. Subtle socioeconomic factors were also evident with cases 4.0 times
      less likely to have additional bathrooms. Lifestyle factors emerged with cases
      2.3 times more likely to have smoked for at least 30 yrs, 3.8 times less likely
      to eat dairy products every week and 2.6 times less likely to have had high blood
      pressure. At interview, these factors were still evident, but cases, unlike
      controls, had reduced their smoking and alcohol consumption and were less likely
      to go out of the home or exercise than before their illness. Within individuals,
      lifestyle consequences of tuberculosis lead to a "healthier" lifestyle on the one
      hand (less smoking and alcohol consumption), but a reduced quality of life
      (social activity) on the other.

PMID- 11829103
TI  - The effects of coronavirus on human nasal ciliated respiratory epithelium.
AB  - Human coronavirus (HCoV) accounts for 15-30% of common colds, but only one case
      report has described the effect of a coronavirus infection, that was
      asymptomatic, on human respiratory epithelium. The authors examined the effects
      of infection with HCoV on ciliary structure and function in healthy volunteers
      infected by intranasal inoculation with HCoV 229E. A further four volunteers were
      sham infected with ultraviolet-inactivated virus. Immediately before inoculation
      (day 0) and 3 days later (day 3), ciliated epithelium was obtained by brushing
      the inferior nasal turbinate. Ciliary beat frequency was determined and beat
      pattern analysed for evidence of dyskinesia (0=normal, 3=severely dyskinetic)
      using digital high-speed video photography. Ciliary ultrastructure was examined
      by transmission electron microscopy. Symptom diaries were kept for the duration
      of the study. All subjects inoculated with HCoV, including the three who did not
      develop symptoms of an upper respiratory tract infection, had disruption of their
      respiratory epithelium on day 3. Although there was no difference in the mean
      ciliary beat frequency between day 0 (11.3 Hz (95% confidence interval (CI): 8.6
      14.0) and day 3 (9.4 Hz (95% CI 7.2-11.6)), there was a significant increase
      (p<0.05) in the ciliary dyskinesia score between day 0 (0.2 (95% CI 0-0.5)) and
      day 3 (1.1 (95% CI 0.5-1.7). In sham-infected subjects, no differences in
      epithelial integrity, or ciliary structure and function were found between day 0
      and day 3. Inoculation of healthy volunteers with human coronavirus caused
      disruption of the ciliated epithelium and ciliary dyskinesia. This is likely to
      impair mucociliary clearance. Damage to the respiratory epithelium, due to human
      coronavirus infection, may occur without overt clinical symptoms.

PMID- 11829104
TI  - The humoral immune response to influenza vaccination in lung transplant patients.
AB  - The purpose of this study was to evaluate the humoral immune response to
      influenza vaccination in lung transplant recipients. Antibody levels to the three
      viral antigens included in the 1999-2000 trivalent influenza vaccine
      (A/Sydney/5/97-like (H3N2), A/Beijing262/95-like (H1N1), and B/Yamanashi/16/ 98)
      were measured before and 4 weeks postvaccination in 43 lung transplant recipients
      and 21 healthy adult controls. The ability to develop protective antibody levels,
      a serological response, and the magnitude of change in levels were assessed. The
      humoral immune response to influenza vaccination was significantly lower in the
      transplant group for all three viral antigens. To A/Sydney, 95% of the control
      group and 40% of the transplant group developed protective levels (p=0.0009); to
      A/Beijing, 71% of the control group and 30% of the transplant group developed
      protective levels (p=0.004); and to B/Yamanashi, 48% of the control group and 19%
      of the transplant group developed protective levels (p=0.02). Those receiving
      cyclosporine had lower antibody responses when compared to those receiving
      tacrolimus (r=-0.3056, p=0.0463). The humoral immune response to influenza
      vaccination in lung transplant recipients is poor. Lung transplant recipients
      receiving cyclosporine may have a lower antibody response than those receiving
      tacrolimus. Alternative prevention strategies may be needed.

PMID- 11829105
TI  - Bronchodilator responsiveness and atopy in 5-10-yr-old coughers.
AB  - Cough-variant asthma is considered by some to be an asthma phenotype.
      Bronchodilator responsiveness (BDR) is an undisputed feature of asthma. Of school
      aged wheezers, 90% are atopic. Are school-aged coughers who demonstrate BDR also
      atopic? If so, then it would be reasonable to reserve the diagnosis cough-variant
      asthma for this particular group. Airway resistance was measured by the
      interrupter technique (Rint) before and after salbutamol in controls (n=73),
      coughers (n=63) and previous wheezers (n=63) aged 5-10 yrs. Immunoglobulin (Ig)-E
      was measured in coughers and wheezers. BDR was expressed as the ratio
      baseline:post-salbutamol Rint. Groups were of similar age (mean 6.7, range 5-9.9
      yrs). Geometric mean baseline Rint was similar in controls and coughers (0.66 and
      0.68 kPa x L(-1) x s), but the baseline Rint for wheezers (0.73 kPa x L(-1) s)
      was greater than that for controls (p=0.05) but not significantly different from
      coughers (p=0.17). Geometric mean BDR in coughers was 1.22, controls 1.13 and
      wheezers 1.30 (p=0.01 for coughers and controls; p=0.08 for coughers and
      wheezers; p<0.001 for controls and wheezers). IgE was lower in coughers than
      wheezers (geometric means 36 and 364 International Units (IU) x L(-1), p<0.001)
      and was unrelated to BDR in both groups. In summary, atopy, and not
      bronchodilator responsiveness, distinguishes groups of coughers from groups of
      wheezers. A diagnosis of cough-variant asthma cannot be reserved for even those
      school-aged coughers, who demonstrate bronchodilator responsiveness.

PMID- 11829106
TI  - Evaluation of the interrupter technique in healthy, unsedated infants.
AB  - The interrupter technique may be used to monitor respiratory resistance and does
      not require active patient cooperation, but has yet to be applied in unsedated,
      spontaneously breathing infants. The aim of this study was to determine if the
      interrupter technique is feasible in spontaneously breathing infants and to
      investigate the influence of facemask types and analysis techniques on the
      interrupter resistance (Rint). Rint was measured in 14 healthy, unsedated,
      sleeping infants (aged 38.4 (31-56) days (mean (range)). Paired measurements were
      made using large volume, compliant (Mcomp) and small volume, rigid (Mrigid)
      facemasks. Flow and pressure were measured at the airway opening prior to- and
      following a brief airway occlusion (500 ms). Rint was calculated using four
      previously reported analysis techniques. Rint could be measured in all infants.
      Mcomp, independent of the analysis method significantly underestimated Rint
      (p<0.001). The variability and magnitude of Rint were significantly influenced by
      the choice of analysis method. The conclusion is that the interrupter technique
      is feasible in spontaneously breathing, unsedated infants. Equipment design and
      analysis method significantly influences interrupter resistance. Studies
      standardizing equipment and identifying the most appropriate analysis technique
      in this age group are needed.

PMID- 11829108
TI  - Controlled, prospective trial of psychosocial function before and after
      continuous positive airway pressure therapy.
AB  - The aim of the study was to investigate psychosocial function before and after
      continuous positive airway pressure (CPAP) therapy, and establish the
      determinants and consequences of objective CPAP use. In a prospective, parallel
      group study, changes in psychosocial scores were compared with conservative
      management or CPAP therapy for the sleep apnoea/hypopnoea syndrome (SAHS).
      Patient/partner couples from the top (CPAP treated, n=44) or bottom
      (conservatively treated, n=25) of a CPAP waiting list rated marital satisfaction
      (evaluation and nurturing relationship issues, communication and happiness
      (ENRICH), behavioural questionnaire), health/functional status (Short-Form-36
      Health Survey, functional outcomes of sleep questionnaire) and sleepiness
      (Epworth sleepiness scale). Both groups' ratings at baseline were completed while
      on conservative therapy. Baseline variables did not differ between groups. At
      follow-up, all seven summary psychosocial scores were statistically better in
      CPAP-treated patients, effect sizes (ES) ranging from moderate (0.5 SD: marital
      satisfaction) to very large (>1.0 SD: patients health, functional status and
      sleepiness scores). Scores in conservatively-treated patients deteriorated to a
      small or moderate degree (ES -0.2- -0.7 SD), while those in the CPAP-treated
      group improved to a larger degree (0.3-1.3 SD). Baseline polysomnographical and
      psychosocial scores, including marital satisfaction, did not predict objective
      CPAP use (r<0.3). CPAP use was modestly correlated (r=0.3-0.6) with improvement
      in all psychosocial areas. Continuous positive airway pressure produced
      statistically and clinically significant psychosocial improvements, some of large
      magnitude, in psychosocial function. Determinants of usage were not identified,
      but benefits and usage were positively correlated.

PMID- 11829107
TI  - Medroxyprogesterone in postmenopausal females with partial upper airway
      obstruction during sleep.
AB  - The aim of the present study was to evaluate the degree and duration of
      respiratory stimulation caused by medroxyprogesterone acetate (MPA), and compare
      the effect of MPA to that of nasal continuous positive airway pressure (nCPAP) in
      sleep-disordered breathing. Ten postmenopausal females with predominantly partial
      upper airway obstruction during sleep had an overnight sleep study at baseline,
      on the fourteenth day of treatment with MPA and after a 3-week washout period.
      Six subjects on nCPAP were also studied 3 months later. At baseline, the
      overnight mean+/-SD end-tidal pressure of carbon dioxide (Pet,CO2) was 5.5+/-0.4
      kPa the arterial oxygen saturation (Sa,O2) 93.0+/-1.2%, Sa,O2 nadir 80.0+/-6.7%,
      and frequency of oxygen desaturation > or = 4% (ODI4) per hour 2.2+/-1.3. MPA
      decreased Pet,CO2 by 0.8 kPa (14.5%, p<0.001). After washout, the mean Pet,CO2
      remained at 0.5 kPa (9.1%, p<0.001) lower than at baseline. Sa,O2 did not change.
      Pet,CO2 was lower on MPA than on nCPAP (4.7+/-0.2 kPa versus 5.0+/-0.3 kPa;
      p=0.037) but Sa,O2 was similar. Apnoea/hypopnoea index tended to be lower on CPAP
      than on MPA. Medroxyprogesterone acetate at a daily dose of 60 mg improves
      ventilation in postmenopausal females with partial upper airway obstruction
      during sleep without compromising sleep. The ventilatory improvement is sustained
      for at least 3 weeks posttreatment. Medroxyprogesterone acetate was more
      efficient in decreasing the partial pressure of carbon dioxide but continuous
      positive airway pressure was superior in decreasing respiratory efforts.

PMID- 11829109
TI  - Synthesis of some new biologically active bis-(thiadiazolotriazines) and bis
      (thiadiazolotriazinyl) alkanes.
AB  - 4-Amino-3-mercapto-1,2,4-triazin-5(4H)-ones (1) were condensed with dicarboxylic
      acids 2 to yield bis-(4-oxo-4H-1,3,4-thiadiazolo[2,3-c]-1,2,4-triazin-7
      yl)alkanes (3b-d,f-h,j-l,n-p) and bis-thiadiazolotriazines (3a,e,i,m). All the
      newly synthesised compounds were characterised by analytical, IR, NMR and mass
      spectral studies. Some of the newly synthesised compounds were screened for their
      antibacterial and antifungal properties. Among the tested compounds, compound
      7,7'-(1,4-butanediyl)-his-(3-t-butyl-4-oxo-4H-1,3,4-thia-diazolo[2,3-c]-1,2,4
      triazine (3p) exhibited highest degree of antifungal activity.

PMID- 11829110
TI  - Synthesis and in vivo pharmacology of new derivatives of isothiazolo[5,4
      b]pyridine of Mannich base type.
AB  - Recently we reported on 2H-4,6-dimethyl-2-[(4-phenylpiperazin-1-yl)methyl]-3-oxo
      2,3-dihydroisothiazolo[5,4-b]pyridine (V), which exhibited high anorectic action
      in animal models as a result of stimulation of serotoninergic system. This paper
      describes the synthesis of the series 3-5 of analogues of V prepared from 2
      hydroxymethyl-4,6-dimethylisothiazolopyridine (2) and corresponding 4-substituted
      piperazines(piperidines) or tetrahydroisoquinoline. The 12 compounds obtained
      were screened in standard CNS tests in in vivo (mice and rats). In contrast to V,
      none of its analogues showed serotoninergic activity, whereas several of these
      compounds were found to be active as weak to moderate analgesic agents. According
      to X-ray and molecular modeling studies the different pharmacological profile of
      V and its o-OCH3 analog 3a, taken as an example, should be referred back to the
      conformational restriction incorporated by the o-substitution rather than effects
      of different lipophlicity or basicity of these compounds.

PMID- 11829111
TI  - Studies on nitrophenylfuran derivatives part Xii. synthesis, characterization,
      antibacterial and antiviral activities of some nitrophenylfurfurylidene-1,2,4
      triazolo[3,4-b]-1,3,4-thiadiazines.
AB  - Synthesis of four 1-aryl-3-[5-(p-nitrophenyl)-2-furyl]-2-propen-1-ones starting
      from substituted acetophenones and p-nitrophenylfurfuraldehyde is described.
      These propenones were then converted into corresponding dibromo derivatives which
      on dehydrobromination afforded alpha-bromopropenones rather than acetylenic
      ketones. Condensation of these dibromopropanones with 4-amino-5-mercapto-1,2,4
      triazoles yielded a new class of nitrophenylfurfurylidene-1,2,4
      triazolothiadiazines. The structures of nitrophenylfurfurylidene-1,2,4
      triazolothiadiazines were established on the basis of analytical, IR, NMR and
      mass spectral studies. The formation of 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazines
      rather than 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazepines in the above condensation
      was unambiguously confirmed by X-ray crystallographic analysis of one of them. A
      possible mechanism is proposed to account for the formation of
      nitrophenylfurfurylidene-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazines. Some of the
      newly synthesized triazolothiadiazines were screened for their antibacterial and
      antiviral properties.

PMID- 11829112
TI  - New 2-(2'-phenyl-9'-benzyl-8'-azapurin-6'-ylamino)-carboxylic acid methylesters
      as ligands for A1 adenosine receptors.
AB  - Synthesis of a series of new 2-phenyl-9-benzyl-8-azaadenines bearing on N6 an
      alkyl or aralkyl chain having a carbonyloxymethyl group on the carbon bound to N6
      were reported. The ester group could assure to the molecule a better water
      solubility than the 8-azaadenines 2, 6 and 9 substituted with lipophilic groups
      synthesised in the past. Compounds synthesised demonstrated only little
      capability of binding A1 adenosine receptors.

PMID- 11829113
TI  - Novel functionalized pyrido[2,3-g]quinoxalinones as antibacterial, antifungal and
      anticancer agents.
AB  - A series of twelve novel pyrido[2,3-g]quinoxalinones (3-14), variously
      substituted at the C-3 position, was synthesized, structurally determined and
      submitted to a preliminary in vitro evaluation for antibacterial, anticandida and
      anticancer activities. Results of the antimicrobial screening showed that all
      compounds, with the exception of 6, 11 and 12, exhibited interesting activity
      against all strains tested; while compound 10 was found to have encouraging in
      vitro anticancer activity at a concentration of l0(-4) M.

PMID- 11829114
TI  - Synthesis and pharmacological activity of 1,2,4-triazolo[4,3-a]quinolines.
AB  - The synthesis of a series of 1,2,4-triazolo[4,3-a]quinoline derivatives is
      described; their structures were assigned by 1H NMR and analytical data. The new
      compounds were tested in vivo for their antiinflammatory and analgesic
      activities, as well as for their ulcerogenic action. Some of the tested triazoles
      showed an analgesic activity in the acetic acid writhing test and
      antiinflammatory properties on carrageenan paw edema assay.

PMID- 11829115
TI  - Synthesis and antimicrobial activity of some 1,2,4-triazole-3-mercaptoacetic acid
      derivatives.
AB  - Ethyl 5-(2-furyl)-4-ethyl-1,2,4-triazole-3-mercaptoacetate (2), 5-(2-furyl)-4
      ethyl-1,2,4-triazole-3-mercaptoacetic acid hydrazide (3) and a series of new N
      alkylidene/arylidene-5-(2-furyl)-4-ethyl-1,2,4-triazole-3-mercaptoacetic acid
      hydrazides (4a-f) were synthesized and evaluated for in vitro antibacterial
      activity against Staphylococcus aureus ATCC 6538. Staphylococcus epidermidis ATCC
      12228, Klebsiella pneumoniae ATCC 4352, Pseudomonas aeruginosa ATCC 1539,
      Escherichia coli ATCC 8739, Shigella flexneri, Salmonella typhi, Proteus
      mirabilis and antifungal activity against Candida albicans ATCC 10231 using the
      disk diffusion and microdilution methods. Compound 4f showed antibacterial
      activity against some bacteria. The in vitro antimycobacterial activity of the
      new compounds against Mycobacterium tuberculosis H37Rv was evaluated employing
      the BACTEC 460 radiometric system. The highest inhibition observed was 61% at >
      6.25 microg/ml.

PMID- 11829116
TI  - Synthesis and structure elucidation of some new thioether derivatives of 1,2,4
      triazoline-3-thiones and their antimicrobial activities.
AB  - 5-(4-Pyridinyl)-4-substituted-2.4-dihydro-3H-1,2,4-triazole-3-thiones and 5-(4
      pyridinyl)-4-substituted-3-(benzoylmethyl)thio-4H-1,2,4-triazoles were
      synthesized. The structures of original nine compounds were confirmed by IR, 'H
      NMR, mass spectral methods and elemental analysis. The antibacterial, antifungal
      and antimycobacterial activities, together with those of known intermediate 1,4
      disubstituted thiosemicarbazides, were reported.

PMID- 11829117
TI  - Thienopyrimidine derivatives prevent cartilage destruction in articular disease.
AB  - The effects of a series of thienopyrimidine derivatives on the prevention of
      cartilage destruction in articular disease were investigated. Anti-degenerative
      activity was assayed on culture of nasal pig cartilage in the presence or in the
      absence of interleukin 1beta (IL-1beta). The amount of glycosaminoglycans (GAGs)
      and the production of nitric oxide (NO) in the culture medium were determined.
      Some thienopyrimidine derivatives, in the presence of IL-beta, blocked the
      cartilage breakdown by inhibiting both the NO production and GAGs release in a
      dose-dependent manner.

PMID- 11829118
TI  - Synthesis and antimicrobial activities of novel naphtho[2,1-b]pyran, pyrano[2,3
      d]pyrimidine and pyrano[3,2-e][1,2,4]triazolo[2,3-c]-pyrimidine derivatives.
AB  - The synthesis of new naphtho[1',2':5,6]pyrano[2,3-d]pyrimidines and related
      heterocycles has been reported. The key intermediate 3-amino-8-bromo-1-(p
      methoxyphenyl)-1H-naphtho[2,1-b] pyran-2-carbonitrile (3c) was obtained in one
      pot synthesis by treating alpha-cyanocinnamonitrile (1c) with 6-bromo-2-naphthol
      (2). Antimicrobial activity was shown for some of the synthesized compounds.

PMID- 11829119
TI  - Synthesis and evaluation of antibacterial activity of some 2-[[alpha-(4
      substituted benzoyloxy)-alpha-phenylacetyl or methylacetyl]amino]-5-(4
      methoxyphenyl)- 1,3,4-oxadiazoles.
AB  - In this study, a new series of 1-[[alpha-(4-substitutedbenzoyloxy)-alpha
      phenylacetyl or methylacetyl]amino]-5-(4-methoxyphenyl)-1,3,4-oxadiazoles were
      obtained by condensation of 2-[(alpha-chloro-alpha-phenylacetyl or alpha
      bromopropionyl)amino]-5-(4-methoxyphenyl)1,3,4-oxadiazoles with sodium salts of 4
      substituted benzoic acids. Structures of the compounds were assigned on the basis
      of spectral data (UV, IR, 1H NMR, El MS) and elemental analyses. The
      antibacterial activities of the novel compounds against Staphylococcus aureus
      ATCC 6538. Staphylococcus epidermidis ATCC 12228, Escherichia coli ATCC 8739,
      Klebsiella pneumoniae ATCC 4352, Pseudomonas aeruginosa ATCC 1539, Salmonella
      typhi, Shigella flexneri and Proteus mirabilis and antifungal activity against
      Candida albicans ATCC 10231 were tested using disk diffusion method. Compounds
      4a, 4d and 4g were found to be active against S. aureus ATCC 6538 (MIC, 78, 39
      and 78 microg ml(-1), respectively) and compound 4e against S. epidermidis ATCC
      12228 (MIC, 156 microg ml(-1)).

PMID- 11829120
TI  - The effects of creatine on the retrogradely perfused isolated rat heart.
AB  - Although the role of creatine in muscle metabolism is well understood, there is
      still uncertainty as to its effects at supplemented levels. With this in mind,
      this study was designed to investigate the direct effects of commercially
      available creatine on the isolated rat heart, retrogradely perfused and infused
      with varying concentrations of creatine (1.25, 2.5, 5 and 10 mM) to determine its
      effects on heart rate, coronary flow and ventricular pressure. Furthermore,
      tissue from these hearts was used to investigate the cardiotoxic potential of
      supplemented levels of creatine. Results indicate that creatine directly improves
      the functioning of the heart under normal conditions with respect to heart rate
      and ventricular pressure, but may be detrimental to the functioning of energy
      deprived hearts. It also showed no cardiotoxic properties since it increased the
      baseline levels of adenosine triphosphate (ATP) and decreased the levels of
      isocitrate dehydrogenase (lCD), indicating a decrease in cellular death compared
      with non-supplemented control hearts.

PMID- 11829121
TI  - Uptake of lamivudine by rat renal brush border membrane vesicles.
AB  - Uptake of lamivudine, a nucleoside analogue antiviral agent, by brush border
      membrane vesicles (BBMV) prepared from rat renal cortex was investigated. Initial
      uptake of lamivudine by BBMV was stimulated in the presence of an outward pH
      gradient. Determination of the kinetic parameters of the initial uptake yielded
      apparent Km and Vmax values of 2.28 mm and 1.56 nmol (mg protein)(-1) (20 s)(-1),
      respectively. The pH-driven uptake of lamivudine was inhibited by organic cations
      such as trimethoprim and cimetidine. The inhibitory effect of trimethoprim on
      lamivudine uptake was competitive, with an apparent Ki of 27.6 microM. The uptake
      of lamivudine was also inhibited by nitrobenzylthioinosine, a representative
      inhibitor of nucleoside transport, and by other nucleoside analogues, such as
      azidothymidine and dideoxycytidine, that are excreted by renal tubular secretion.
      These findings suggest that efflux of lamivudine at the brush border membrane of
      renal tubular epithelium is mediated by an H+/lamivudine antiport system, which
      may correspond to the H+/organic cation antiport system, and that this system is
      also involved in the renal secretion of other nucleoside analogues.

PMID- 11829122
TI  - Curcumin inhibits collagen synthesis and hepatic stellate cell activation in-vivo
      and in-vitro.
AB  - We previously demonstrated that curcumin, a well-known antioxidant, inhibits
      collagen deposition in carbon tetrachloride-induced liver injury in rats. The
      major effector cells responsibleforcollagensynthesis in the liver are activated
      hepatic stellate cells. In this study,we investigated the inhibitory effects of
      curcumin on the collagen synthesis and activation of rat hepatic stellate cells
      in-vitro, and on hepatic stellate cell activation in-vivo. The effects of
      curcumin on the production of collagen and smooth muscle alpha-actin proteins and
      of alpha1(I) collagen mRNA were studied in-vivo and in-vitro. The effect of
      curcumin on DNA synthesis was also determined in-vitro. In-vivo, treatment with
      curcumin reduced collagen deposition and smooth muscle alpha-actin-positive areas
      and lowered mRNA levels of type I collagen in the liver. In-vitro, curcumin at a
      concentration of 5 microg mL(-1) reduced DNA synthesis, and downregulated smooth
      muscle alpha-actin and type I collagen expression, and alpha1(I) collagen mRNA
      expression. We concluded that curcumin inhibits collagen synthesis and hepatic
      stellate cell activation in-vivo and in-vitro, and thus may prove a valuable anti
      fibrogenic agent.

PMID- 11829123
TI  - The effect of clonidine on the naltrexone-induced withdrawal response in morphine
      treated guinea-pigs.
AB  - Rapid opioid withdrawal induced by naltrexone is now used as a treatment for
      heroin addiction. The alpha2-adrenoceptor agonist, clonidine, is currently used
      in clinical practice to reduce opioid withdrawal in humans. However, few studies
      have been reported on its effectiveness for this purpose. Guinea-pigs were made
      dependent and tolerant to morphine using a 3-day chronic morphine regimen (total
      410 mg kg(-1) morphine base), and injected with either clonidine (0.1 mg kg(-1),
      s.c.) or saline, 1 h before induction of withdrawal with naltrexone (15 mg kg(
      1), s.c.). Withdrawal behaviours were measured for 90 min and animals were then
      euthanased and the brains removed. The presence of the immediate early gene
      protein product, c-Fos, was detected using immunohistochemical techniques.
      Clonidine reduced the number of head/body shakes, but had no effect on the total
      withdrawal behaviour score. In the CNS, clonidine increased the number of Fos-LI
      neurons in the central amygdala. In conclusion, the modest effect of clonidine in
      the present experiments suggests that the efficacy of clonidine in humans
      undergoing naltrexone-induced opioid withdrawal requires further investigation.

PMID- 11829124
TI  - Synergistic effect of nicorandil and amlodipine on mitochondrial function during
      isoproterenol-induced myocardial infarction in rats.
AB  - The synergistic effects of nicorandil (KATP-channel opener) and amlodipine
      (calcium-channel blocker) on heart mitochondrial enzymes and the mitochondrial
      antioxidant defence system was examined on isoproterenol-induced myocardial
      infarction in rats. The rats given isoproterenol (150 mg kg(-1) daily, i.p.) for
      two days showed significant changes in marker enzymes, mitochondrial enzymes and
      the mitochondrial defence system. Pre-co-treatment with nicorandil (2.5 mg kg(-1)
      daily, p.o.) and amlodipine (5.0 mg kg(-1) daily, p.o.) for 3 days significantly
      prevented these alterations and restored enzyme activity to near normal. These
      findings demonstrate the protective and synergistic effect of nicorandil and
      amlodipine in combination against isoproterenol-induced cardiac damage.

PMID- 11829125
TI  - Alpha-adrenergic responsiveness in rat isolated perfused heart after abdominal
      aortic coarctation.
AB  - Chronic isoproterenol pre-treatment, a well-known model of compensatory
      hypertrophy associated with cardiac beta-adrenoceptor desensitization, enhances
      the inotropic response to phenylephrine in rat isolated perfused hearts,
      supporting the hypothesis that myocardial alpha-adrenoceptor stimulation
      contributes to the maintenance of myocardial performance in situations in which
      cardiac beta-adrenoceptor function is compromised. To further corroborate this
      hypothesis, the effects of abdominal aortic coarctation on cardiac alpha
      adrenergic responsiveness were investigated in Langendorff heart preparations.
      Abdominal aortic coarctation causes cardiac hypertrophy (21%) as shown by a
      significant increase in the ratio of ventricular dry weight to bodyweight. In
      preparations from hypertrophied rats, both maximum increases in left ventricular
      systolic pressure and heart rate elicited by isoproterenol (10(-12) to 10(-4) M)
      were significantly reduced (the isoproterenol concentration producing 50% of the
      maximum positive inotropic and chronotropic responses was enhanced almost 21- and
      2-fold, respectively). However, the positive inotropic response to phenylephrine
      (10(-12) to 10(-4) M) remained unaffected following abdominal aortic coarctation,
      when compared with sham-operated rats. In preparations from both groups,
      phenylephrine infusion did not induce significant changes in heart rate. These
      results show that although abdominal aortic stenosis induced desensitization of
      cardiac beta-adrenoceptors, it did not enhance cardiac alpha-adrenoceptor
      responsiveness. This suggests that such an enhancement depends on the
      experimental model used to induce cardiac hypertrophy associated with
      desensitization of cardiac beta-adrenoceptors.

PMID- 11829126
TI  - Design, synthesis and biological evaluation of novel beta-substituted indol-3-yl
      ethylamido melatoninergic analogues.
AB  - A series of new melatonin analogues have been synthesized. Interestingly, two of
      the new compounds, 11c and 11e, which did not show any appreciable affinity for
      the melatonin receptor, were found to be potent inhibitors of lipid peroxidation
      in rat liver microsomes. Analogue 11c, in particular, is a better antioxidant
      than melatonin.

PMID- 11829127
TI  - Vehicles for oligonucleotide delivery to tumours.
AB  - The vasculature of a tumour provides the most effective route by which neoplastic
      cells may be reached and eradicated by drugs. The fact that a tumour's
      vasculature is relatively more permeable than healthy host tissue should enable
      selective delivery of drugs to tumour tissue. Such delivery is relevant to
      carrier-mediated delivery of genetic medicine to tumours. This review discusses
      the potential of delivering therapeutic oligonucleotides (ONs) to tumours using
      cationic liposomes and cyclodextrins (CyDs), and the major hindrances posed by
      the tumour itself on such delivery. Cationic liposomes are generally 100-200 nm
      in diameter, whereas CyDs typically span 1.5 nm across. Cationic liposomes have
      been used for the introduction of nucleic acids into mammalian cells for more
      than a decade. CyD molecules are routinely used as agents that engender
      cholesterol efflux from lipid-laden cells, thus having an efficacious potential
      in the management of atherosclerosis. A recent trend is to employ these
      oligosaccharide molecules for delivering nucleic acids in cells both in-vitro and
      in-vivo. Comparisons are made with other ON delivery agents, such as porphyrin
      derivatives (< 1 nm), branched chain dendrimers (approximately 10 nm),
      polyethylenimine polymers (approximately 10 nm), nanoparticles (20-1,000 nm) and
      microspheres (> 1 microm), in the context of delivery to solid tumours. A
      discourse on how the chemical and physical properties of these carriers may
      affect the uptake of ONs into cells, particularly in-vivo, forms a major basis of
      this review.

PMID- 11829129
TI  - pH-sensitive, serum-stable and long-circulating liposomes as a new drug delivery
      system.
AB  - The lack of stability in blood and the short blood circulation time of pH
      sensitive liposomes are major drawbacks for their application in-vivo. To develop
      pH-sensitive, serum-stable and long-circulating liposomes as drug delivery
      systems, the impact of polyethylene glycol-derived phosphatidylethanolamine (DSPE
      PEG) on the properties of pH-sensitive liposomes was investigated. pH-sensitive
      liposomes were prepared with dioleoylphosphatidylethanolamine (DOPE) and oleic
      acid (DOPE/oleic acid liposome) or DOPE and 1,2-dipalmitoylsuccinylglycerol
      (DOPE/DPSG liposome). The inclusion of DSPE-PEG enhanced the serum stability of
      both DOPE/oleic acid and DOPE/DPSG liposomes, but also shifted the pH-response
      curve of pH-sensitive liposomes to more acidic regions and reduced the maximum
      leakage percentage. The impact of DSPE-PEG, however, was much lower in the
      DOPE/DPSG liposomes than in the DOPE/oleic acid liposomes. In tumour tissue
      homogenates, where the pH is lower than normal healthy tissues, the pH-sensitive
      DOPE/DPSG liposomes released the entrapped markers rapidly, in comparison with pH
      insensitive dipalmitoylphosphatidylcholine/cholesterol/DSPE-PEG liposomes.
      Moreover, the release rate was not affected by the content of DSPE-PEG. The blood
      circulation time of methotrexate incorporated in DOPE/UDPSG liposomes was
      significantly prolonged with increasing content of DSPE-PEG. Taken together, the
      liposomes composed of DOPE, DPSG and DSPE-PEG (up to 5%) were pH sensitive,
      plasma stable and had a long circulation time in the blood. The complete
      destabilization of the liposomes at tumour tissues suggests that the liposomes
      might be useful for the targeted delivery of drugs such as anticancer agents.

PMID- 11829128
TI  - Microemulsion formulation of clonixic acid: solubility enhancement and pain
      reduction.
AB  - Clonixic acid is currently marketed as a salt form because of its poor water
      solubility. However, the commercial dosage form causes severe pain after
      intramuscular or intravenous injection. To improve the solubility of clonixic
      acid and to reduce pain on injection, clonixic acid was incorporated into oil-in
      water microemulsions prepared from pre-microemulsion concentrate composed of
      varying ratios of oil and surfactant mixture. As an oil phase for drug
      incorporation, up to 14% castor oil could be included in the pre-microemulsion
      concentrate without a significant increase in droplet size. Both drug contents
      and droplet size increased as the weight ratio of Tween 20 to Tween 85 decreased.
      Taken together, when microemulsions were prepared from pre-microemulsion
      concentrate composed of 5:12:18 weight ratio of castor oil:Tween 20:Tween 85,
      clonixic acid could be incorporated at 3.2 mg mL(-1) in the microemulsion with a
      droplet size of less than 120 nm. The osmotic pressure of this microemulsion was
      remarkably lower than the commercial formulation, irrespective of the dilution
      ratios. The rat paw-lick test was used to compare pain responses among
      formulations. The microemulsion formulation significantly reduced the number of
      rats licking their paws as well as the total licking time, suggesting less pain
      induction by the microemulsion formulation. The pharmacokinetic parameters of
      clonixic acid after intravenous administration of the clonixic acid microemulsion
      to rats were not significantly different from those of the commercial
      formulation, lysine clonixinate. The present study suggests that microemulsion is
      an alternative formulation for clonixic acid with improved characteristics.

PMID- 11829130
TI  - Monoclonal anti-epidermal growth factor receptor (ior EGF/r3) antibody
      pharmacokinetic studies on nude mice I: a radio-receptor analysis applied to drug
      serum quantification.
AB  - Due to its antagonistic properties upon ligand-epidermal growth factor receptor
      (EGFr) interaction, the monoclonal antibody anti-EGFr ior EGF/r3 is considered a
      potential therapeutic agent against several epithelium-derived tumours. This
      paper affords further analysis of the relevant corporal interaction of this
      monoclonal antibody in terms of its pharmacodynamic properties, using nude mice,
      following a single bolus intravenous dose administration. The radio-receptor
      assay allows quantification of the serum ior EGF/r3 level. The dose selection
      procedure, according to the Kolmogorov-Smirnov test, suggested using doses of
      12.5-16 mg kg(-1) for pharmacokinetic assessments. The experimental data were
      best fitted to a bi-exponential function (r2 = 0.985), through the classical two
      compartment open modelling approach. The model selection was corroborated by the
      AKAIKE information criteria, and also the SCHWARTZ and ESTRIP test were used. The
      estimated pharmacokinetic parameters (e.g. t 1/2 beta = 34.65 h, Vc = 2.84 mL,
      Vss = 4.21 mL and CL = 0.09 mL h(-1)) bear out the strategies for the evaluation
      of the therapeutic application of this drug. Finally, the radio-receptor analysis
      has provided a rationale for the proposed serum monoclonal antibody ior EGF/r3
      quantification to characterize its concentration-time course.

PMID- 11829131
TI  - Evaluation of increased bioavailability of tacrolimus in rats with experimental
      renal dysfunction.
AB  - The effects of renal failure on the hepatic and intestinal extraction of
      tacrolimus were evaluated to examine the mechanisms for the increased
      bioavailability of this drug in cisplatin-induced renal failure model rats.
      Tacrolimus extractions in the liver and intestine were evaluated by intravenous,
      intraportal and intraintestinal infusion. The intestinal metabolism and
      absorption rate were estimated by incubating the isolated intestine with drug
      solution and by an in situ loop method, respectively. Blood concentrations of
      tacrolimus following the intraintestinal infusion were significantly increased in
      rats with renal failure compared with those in normal rats. The blood
      concentration of tacrolimus during intraportal infusion in rats with renal
      failure showed non-linearity against dose, and was increased as compared with
      that in normal rats. The intestinal metabolism was not altered, but the
      absorption rate was significantly increased in the intestine from rats with renal
      dysfunction. These results suggest that the hepatic metabolism of tacrolimus is
      impaired in rats with renal failure, and that the accelerated absorption rate in
      the intestine in renal dysfunction is followed by partial saturation of hepatic
      extraction, which may be one of the mechanisms of increased bioavailability of
      tacrolimus.

PMID- 11829132
TI  - Pharmacokinetics of ABT-773, a new semi-synthetic ketolide in neutropenic lung
      infected mice: a population approach.
AB  - ABT-773 is an investigational ketolide antimicrobial agent with an in-vitro
      bactericidal activity against macrolide-susceptible and -resistant Streptococcus
      pneumoniae. The pharmacokinetics of this drug candidate were evaluated in lung
      infected (108 CFU mL 1 starting inoculum) mice following a single dose (25, 50,
      100 or 200 mg kg(-1)) oral administration as a solution in 10% of 95% ethanol and
      90% of 0.1 M pH 6.5 phosphate buffer solution. Serum ABT-773 concentrations were
      measured using a validated HPLC assay with fluorescence detection (excitation at
      324 nm and emission at 364 nm). Population pharmacokinetic analysis was performed
      using the NONMEM computer program. Results from data analysis showed non-linear
      pharmacokinetics of ABT-773, noted by the increases in half-life (3.1 to 27.2 h)
      and AUC/dose (23.7 to 149 mg h(-1) L(-1) mg(-1)), with doses from 25 to 200 mg
      kg(-1). A non-linear one-compartment model with parallel capacity-limited and
      linear first-order elimination best described the pharmacokinetics of ABT-773 in
      the mouse. The total volume of distribution was 0.316 L. The clearance for the
      linear first-order elimination was 0.0027 L h(-1). The Vm and Km were 0.0385 L h(
      1) and 0.141 mg L(-1), respectively, for the capacity-limited elimination.

PMID- 11829133
TI  - Effect of 7-day exposure to midazolam on electroencephalogram pharmacodynamics in
      rats: a model to study multiple pharmacokinetic-pharmacodynamic relationships in
      individual animals.
AB  - The objective of this study was to determine the concentration
      electroencephalogram (EEG) relationships for midazolam, a full-agonist
      benzodiazepine ligand, on multiple occasions in individual rats, and to examine
      the effect of chronic midazolam exposure on that relationship. Rats were
      chronically instrumented with venous and arterial cannulas, and cortical EEG
      electrodes. The rats received either: 7 days of midazolam 10 mg kg(-1)
      intravenously once a day (midazolam group); or midazolam on days 1 and 7 and
      vehicle on days 2-6 (vehicle group). Concentration-effect relationships were
      determined on days 1, 4 and 7 from multiple blood and EEG samples before and
      after the administration of the midazolam dose. The concentration-EEG effect
      relationships were consistent with a sigmoidal Emax (maximal effect) model. No
      differences in pharmacokinetic or pharmacodynamic parameters were found between
      day 1 and day 7 in either group. However, in the midazolam group, both the
      fraction unbound of midazolam in serum and the EC50 (concentration at half
      maximal effect) for free midazolam increased from days 1-7 by 35 +/- 3% and 54 +/
      25%, respectively (means +/- s.d., P< 0.05). This may be related to decreased
      serum albumin levels in the midazolam group (-19+5%, P < 0.05) which, in turn,
      could be explained by the sedation associated with daily midazolam treatment. We
      concluded that concentration-EEG effect relationships can be studied on multiple
      occasions in individual animals, reducing animal use and variability. A modest
      degree of tolerance to midazolam was found with this paradigm, the effect only
      being evident after correction for the fraction unbound of midazolam.

PMID- 11829134
TI  - Impurity profiling of pholcodine by liquid chromatography electrospray ionization
      mass spectrometry (LC-ESI-MS).
AB  - Previously, a dimorpholinoethyl pholcodine manufacturing impurity was reported to
      be present in some samples of pholcodine. Apart from this impurity and morphine,
      other unknown impurities were detected in all the samples analysed by HPLC and
      micellar electrokinetic capillary chromatography. In this study, liquid
      chromatography mass spectrometry (LC-MS) analysis of samples of pholcodine showed
      that two of the previously unidentified compounds had mass spectra with molecular
      ions which differed from pholcodine by 16 amu. From this observation and other
      experimental data it was concluded that they are hydroxy derivatives of
      pholcodine. 10-S-hydroxy-pholcodine, which was synthesized by the oxidation of
      pholcodine with chromic acid, had the same chromatographic properties as one of
      these compounds. An early eluting compound in the LC-MS chromatograms of
      pholcodine was identified as pholcodine-N-oxide by matching chromatographic and
      mass spectral data of a synthesized pholcodine-N-oxide standard. The reaction of
      pholcodine with m-chloroperoxybenzoic acid not only produced the mono N-oxide,
      but also pholcodine-di-N,N'-oxide.

PMID- 11829135
TI  - Spasmolytic effects of baccharis conferta and some of its constituents.
AB  - The Nahua of the Mexican state of Veracruz use Baccharis conferta in the
      treatment of a variety of gastrointestinal illnesses, especially diarrhoea
      associated with gastrointestinal cramps. The aerial parts of B. conferta were
      investigated phytochemically and pharmacologically using the guinea pig ileum
      assay as a model (histamine, KCI and electric stimulation). The crude ethanolic
      extract showed a dose-dependent antispasmodic effect that was particularly strong
      in flavonoid-rich fractions (e.g. IC50 value for fraction E.3.1 from the ethyl
      acetate fraction, in histamine-induced contraction, 10 microg mL(-1)). Several
      flavonoids (apigenin-4',7-dimethylether, naringenin-4',7-dimethylether,
      pectolinarigenin and cirsimaritin) were isolated, while others were identified in
      complex fractions by GC-MS. The flavonoids play an important role in the
      antispasmodic activity of this indigenous drug. Additionally, oleanolic acid and
      its methyl ester as well as erythrodiol were isolated. Oleanolic acid methyl
      ester shows weak antibacterial activity against M. luteusand E. coli (20
      microg/spot in a TLC assay). The phytochemical as well as the pharmacological
      data provide some in-vitro evidence forthe use of B. conferta in thetreatment of
      gastrointestinal cramps.

PMID- 11829136
TI  - Polymorphic sequences of the tyrosinase gene: allele analysis on 16 OCA1 patients
      in Japan indicate that three polymorphic sequences in the tyrosinase gene
      promoter could be powerful markers for indirect gene diagnosis.
AB  - Since 1989, a large number of mutations of the tyrosinase gene, which result in
      oculocutaneous albinism (OCA), have been reported. However, approximately 15% of
      patients with tyrosinase-related OCA (OCA1) heterozygously carried an
      uncharacterized mutation, which presumably existed outside of the ordinarily
      examined area of the tyrosinase gene. In such cases, polymorphic sequence(s) of
      the tyrosinase gene might be useful to identify the OCA1 allele. In this study,
      we examined four polymorphic sequences of the tyrosinase gene in 16 patients with
      OCA1, their relatives, and 108 normally pigmented Japanese individuals. The
      results showed a complex dinucleotide repeat in the promoter region at -800 to 
      900 of seven different lengths, and a polythymidine sequence in the 3' end of
      intron 2 of three different lengths. Polymerase chain reaction-restriction
      fragment length polymorphism analysis of two polymorphic sequences at -301 (C/T)
      and -199 (C/A) in the promoter region allows us to classify the tyrosinase gene
      into three groups. Using these polymorphic sequences, we could identify the OCA1
      allele in more than 80% of cases in which the parents' genomic DNA was available.
      Three polymorphic sequences in the tyrosinase gene promoter are particularly
      useful for this purpose.

PMID- 11829137
TI  - Catalog of 77 single-nucleotide polymorphisms (SNPs) in the carbohydrate
      sulfotransferase 1 (CHST1) and carbohydrate sulfotransferase 3 (CHST3) genes.
AB  - Individual phenotypes with respect to drug response or toxicity often result from
      genetic variations that alter drug metabolism. We have been focusing on genomic
      loci that encode various enzymes and transporters involved in the metabolism of
      drugs, and have described more than 1200 single-nucleotide polymorphisms (SNPs)
      and other variations. Regarding the carbohydrate sulfotransferase (CHST) gene
      family, we have already constructed high-density SNP maps of three genomic
      segments that included CHST2, CHST4, and CHST5, providing a total of 28 SNPs for
      those loci. In the present study, we screened DNA from 48 healthy Japanese
      volunteers for SNPs at the CHST1 and CHST3 gene loci, by means of direct
      sequencing combined with a polymerase chain reaction method for amplifying
      genomic DNA, and characterized 77 SNPs and four insertion-deletion polymorphisms.
      The collection of human variations presented here adds to the archive of tools
      now available for investigating complex genetic diseases, population migration
      patterns, and a variety of pharmacogenetic possibilities.

PMID- 11829138
TI  - Mutation analysis of the TSC1 and TSC2 genes in Japanese patients with pulmonary
      lymphangioleiomyomatosis.
AB  - Pulmonary lymphangioleiomyomatosis (LAM) is a destructive lung disease
      characterized by a diffuse hamartomatous proliferation of smooth muscle cells
      (LAM cells) in the lungs. Pulmonary LAM can occur as an isolated form (sporadic
      LAM) or in association with tuberous sclerosis complex (TSC) (TSC-LAM), a genetic
      disorder with autosomal dominant inheritance with various expressivity resulting
      from mutations of either the TSC1 or TSC2 gene. We examined mutations of both TSC
      genes in 6 Japanese patients with TSC-LAM and 22 patients with sporadic LAM and
      identified six unique and novel mutations. TSC2 germline mutations were detected
      in 2 (33.3%) of 6 patients with TSC-LAM and TSC1 germline mutation in 1 (4.5%) of
      22 sporadic LAM patients. In accordance with the tumor-suppressor model, loss of
      heterozygosity (LOH) was detected in LAM cells from 3 of 4 patients with TSC-LAM
      and from 4 of 8 patients with sporadic LAM. Furthermore, an identical LOH or two
      identical somatic mutations were demonstrated in LAM cells microdissected from
      several tissues, suggesting LAM cells can spread from one lesion to another. Our
      results from Japanese patients with LAM confirmed the current concept of
      pathogenesis of LAM: TSC-LAM has a germline mutation but sporadic LAM does not;
      sporadic LAM is a TSC2 disease with two somatic mutations; and a variety of TSC
      mutations causes LAM. However, our study indicates that a fraction of sporadic
      LAM can be a TSC1 disease; therefore, both TSC genes should be examined, even for
      patients with sporadic LAM.

PMID- 11829139
TI  - Novel missense mutations in the human lysosomal sialidase gene in sialidosis
      patients and prediction of structural alterations of mutant enzymes.
AB  - Three novel missense mutations in the human lysosomal sialidase gene causing
      amino acid substitutions (P80L, W240R. and P316S) in the coding region were
      identified in two Japanese sialidosis patients. One patient with a severe,
      congenital form of type 2 sialidosis was a compound heterozygote for 239C-to-T
      (P80L) and 718T-to-C (W240R). The other patient with a mild juvenile-onset
      phenotype (type 1) was a homozygote for the base substitution of 946C-to-T
      (P316S). None of these mutant cDNA products showed enzymatic activity toward an
      artificial substrate when coexpressed in galactosialidosis fibroblastic cells
      together with protective protein/cathepsin A (PPCA). All mutants showed a
      reticular immunofluorescence distribution when coexpressed with the PPCA gene in
      COS-1 cells, suggesting that the gene products were retained in the endoplasmic
      reticulum/Golgi area or rapidly degraded in the lysosomes. Homology modeling of
      the structural changes introduced by the mutations predicted that the P80L and
      P316S transversions cause large conformational changes including the active site
      residues responsible for binding the sialic acid carboxylate group. The W240R
      substitution was deduced to influence the molecular surface structure of a
      limited region of the constructed models, which was also influenced by previously
      identified V217M and G243R transversions.

PMID- 11829140
TI  - Three hundred twenty-six genetic variations in genes encoding nine members of ATP
      binding cassette, subfamily B (ABCB/MDR/TAP), in the Japanese population.
AB  - We screened DNAs from 48 Japanese individuals for single-nucleotide polymorphisms
      (SNPs) in nine genes encoding components of ATP-binding cassette subfamily B
      (ABCB/MDR/TAP) by directly sequencing the entire applicable genomic regions
      except for repetitive elements. This approach identified 297 SNPs and 29
      insertion/deletion polymorphisms among the nine genes. Of the 297 SNPs, 50 were
      identified in the ABCB1 gene, 14 in TAP], 35 in TAP2, 48 in ABCB4, 13 in ABCB7,
      21 in ABCB8, 21 in ABCB9, 13 in ABCB10, and 82 in ABCB11. Thirteen were located
      in 5' flanking regions, 237 in introns, 37 in exons, and 10 in 3' flanking
      regions. These variants may contribute to investigations of possible correlations
      between genotypes and disease-susceptibility phenotypes or responsiveness to drug
      therapy.

PMID- 11829141
TI  - Genotypes of autosomal dominant polycystic kidney disease in Japanese.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common
      hereditary disorders. The prevalence of the ADPKD genotype in the Caucasian and
      Latin populations has been reported. Here, we used linkage analysis to
      demonstrate the prevalence of the genotype and the correlation between phenotypes
      and genotypes among 21 Japanese ADPKD families consisting of 96 individuals and
      including 57 affected members. Six polymorphic markers, each linked to either the
      polycystic kidney disease 1 (PKD1) or polycystic kidney disease 2 (PKD2) gene,
      were used for polymerase chain reaction analysis. Seventeen families (81%) showed
      linkage to PKD1, two families (10%) showed linkage to PKD2, and two families did
      not show linkage to either PKD1 or PKD2. One of the PKD1-linked families was
      indicated to have different mutations of PKD1 gene in the same family. PKD2
      linked families did not have milder symptoms than PKD1-linked families.

PMID- 11829142
TI  - Molecular cloning and functional analysis of a factor that binds to the proximal
      promoter of human angiotensinogen.
AB  - A significant association has been reported between a common variant in the
      angiotensinogen gene (AGT), allele T235, and essential hypertension. In
      subsequent work, it was found that another variant, the presence of an adenine
      instead of a guanine 6bp upstream from the initiation site of transcription, was
      in absolute linkage disequilibrium with T235. The nucleotide substitution at the 
      6 position affected the formation of DNA-protein complexes in gel mobility shift
      assays and the basal transcription of AGT in transactivation experiments. We have
      further examined the potential impact of this polymorphism on AGT promoter
      function. In ultraviolet cross-linking analysis. 150- and 75-kDa proteins bound
      to the AGT proximal promoter. The possible involvement of factors that bind to GC
      rich domains, including Sp1, Sp3, and AP2, was not supported by gel mobility
      shift assays. Screening an expression library with a double-stranded DNA segment
      centered on -6 led to the isolation of cDNA clones encoding the YB1 protein. The
      specificity of the interaction of YB1 with the proximal promoter of AGT was
      verified by Southwestern blotting and gel mobility shift assays. In
      cotransfection experiments, YB1 reduced basal AGT promoter activity in a dose
      dependent manner. Although these observations suggest a possible role for YB1 in
      modulating AGT expression, this function is likely to occur in the context of
      complex interactions involving other nuclear factors. The work illustrates the
      challenge of developing a molecular understanding of the relationship between
      common genetic variants and conditions that are only partly caused by them.

PMID- 11829143
TI  - Dissecting receptor-mediated Ca2+ influx pathways: TRP channels and their native
      counterparts.
AB  - Cellular stimulation from the surrounding extracellular environment via receptors
      and other pathways evoke activation of Ca2+-permeable cation channels that form
      essential signaling pathways in controlling biological responses. An important
      clue to understand the molecular mechanisms underlying these cation channels
      (tentatively termed as receptor-mediated cation channels (RMCC)) was first
      provided through molecular studies of the transient receptor potential (trp)
      protein (TRP), which controls light-induced depolarization in Drosophila
      photoreceptor cells. Use of the genetic information and recombinant expression
      technique lead to the discovery of numerous mammalian TRP homologues revealing
      novel RMCCs. In this review, we focus on the dramatic progress in the molecular
      investigation of RMCC in mammalian systems. The recent findings should provide
      powerful tools for the development of novel pharmaceutical targets.

PMID- 11829144
TI  - Absence of endothelium in invertebrate blood vessels: significance of endothelium
      and sympathetic nerve/medial smooth muscle in the vertebrate vascular system.
AB  - In the course of evolution, two remarkable changes seem to have occurred in
      vertebrate circulation: the appearance and development of the "endothelium or
      endothelial tubular system" and "sympathetic nerve/medial smooth muscle system".
      In the present article, some relevant literature is reviewed and discussed.
      Absence of endothelium in the vascular wall of most invertebrates had been known
      and was confirmed by recent electron microscopic studies. The medial smooth
      muscle is rather proper to vertebrate vessels. It seems to have appeared after
      emergence of and in association with the endothelial tubular system.
      Phylogenetically, the parasympathetic nervous system is thought to be older than
      the sympathetic system. The former is distributed to viscera and the latter
      developed in close relation with the vascular system. It is assumed that during
      evolution, a circulatory system composed of the heart and endothelial tubular
      system first formed in vertebrates, medial smooth muscle then appeared for
      regulation of the system, and innervation of the muscle tissue took place. This
      sequence of development assumed for phylogenesis is actually realized in the
      ontogenetic processes. We thus propose a hypothesis that the "sympathetic
      nerve/medial smooth muscle system" may be regarded as a new neuroeffector
      mechanism that developed for systemic regulation of the endothelium-lined closed
      vascular system in vertebrates. A few implications of the hypothesis are
      presented.

PMID- 11829145
TI  - Spinorphin, an endogenous inhibitor of enkephalin-degrading enzymes, potentiates
      leu-enkephalin-induced anti-allodynic and antinociceptive effects in mice.
AB  - Spinorphin (LVVYPWT) has been isolated from the bovine spinal cord as an
      endogenous inhibitor of enkephalin-degrading enzymes. It has been reported that
      spinorphin has an antinociceptive effect, inhibitory effect on contraction of
      smooth muscle and anti-inflammatory effect. In the present study, the effects of
      leu-enkephalin and spinorphin on allodynia and mechanical and thermal
      nociceptions were examined in vivo using mice. Intrathecal (i.t.) administration
      of leu-enkephalin or spinorphin inhibited the allodynia induced by intrathecal
      nociceptin in a dose-dependent manner. Furthermore, spinorphin enhanced the
      inhibitory effect of enkephalin on allodynia induced by nociceptin. Naloxone
      antagonized both inhibitory effects of leu-enkephalin and spinorphin, suggesting
      that the endogenous opioidergic system can modulate allodynia.
      Intracerebroventricular (i.c.v.) administration of leu-enkephalin increased the
      nociceptive threshold of heat or mechanical stimulation to a mouse. Although
      i.c.v. administration of spinorphin had no effect on the threshold of heat or
      mechanical stimulation, spinorphin enhanced and prolonged the antinociceptive
      effect of leu-enkephalin. The enhancement of spinorphin on the antinociception
      produced by leu-enkephalin was reversed by pretreatment with naloxone. From these
      results, it is suggested that the effects of spinorphin on enkephalin-induced
      anti-allodynic and antinociceptive effects are due to inhibition of enkephalin
      degrading enzymes.

PMID- 11829146
TI  - Involvement of potassium channels in spinal antinociceptions induced by fentanyl,
      clonidine and bethanechol in rats.
AB  - In the central nervous systems, intracellular and extracellular movement of
      potassium ions plays an important role in regulating neuronal excitability and
      the release of neurotransmitters. The purpose of our study was to determine
      whether nicorandil (adenosine triphosphate-sensitive K+ channel opener) exerts
      antinociceptive effects by itself or in combination with fentanyl, clonidine and
      bethanechol and whether glibenclamide (adenosine triphosphate-sensitive K+
      channel blocker) and charybdotoxin (Ca2+-activated K+ channel blocker) may
      antagonize the antinociceptive action of fentanyl, clonidine and bethanechol.
      Antinociceptive effects were assessed using the tail-flick test in rats.
      Nicorandil (100 microg) and antinociceptively ineffective doses of fentanyl (1
      microg), clonidine (2.5 microg) or bethanechol (10,ug) were coadministered
      intrathecally (i.t.). Glibenclamide (100 microg) or charybdotoxin (2.5 ng) were
      administered i.t. at 5 min before each effective dose of fentanyl (2.5 microg),
      clonidine (10 microg) or bethanechol (40 microg). The present findings
      demonstrated that i.t. administration of nicorandil alone exerted no influence on
      the tail-flick latency. However, concomitant administrations of antinociceptively
      inactive doses of fentanyl, clonidine or bethanechol with nicorandil elicited
      significant suppression of the thermonociceptive response. Also, each
      antinociception induced by fentanyl, clonidine or bethanechol was partially
      antagonized by both glibenclamide and charybdotoxin. These findings showed that
      activation of the K+ channel might enhance the antinociceptive effects of
      fentanyl, clonidine and bethanechol.

PMID- 11829147
TI  - Role of dopaminergic system in core part of nucleus accumbens in hyperlocomotion
      and rearing induced by MK-801 in rats: a behavioral and in vivo microdialysis
      study.
AB  - We investigated modification of the MK-801 effect on motor activity and
      extracellular amines concentration by 6-hydroxydopamine (6-OHDA)-induced lesion
      of core nucleus accumbens (cACC) of rats. In vivo microdialysis-HPLC showed that
      the concentrations (fmol/microl) of dopamine (DA), dihydroxyphenylacetic acid
      (DOPAC) and serotonin were 0.738 +/- 0.135, 155.34 +/- 41.01 and 0.334 +/- 0.024,
      respectively, in the cACC of intact rats. The DOPAC/DA ratio was 264.24 +/-
      94.01. Unilateral lesion of the cACC with 6-OHDA (8 microg/microl) substantially
      reduced DA (-93%) and DOPAC (-97%) in desipramine (30 mg/kg, i.p.)-pretreated
      rats (6-OHDA+DMI rats) as compared to the 65% reduction rate of both amines in
      saline-pretreated rats (6-OHDA+saline rats). Moreover, DOPAC was reduced by 72%
      in 6-OHDA+DMI rats. MK-801 increased DOPAC (426-467%) and DOPAC/DA ratio (180
      230%) in intact rats. On the other hand, MK-801 increased DA by 154% and 505% in
      6-OHDA+saline and 6-OHDA+DMI rats, respectively. 6-OHDA reduced the effect of MK
      801 on DOPAC and DOPAC/DA ratio. In the behavioral studies, MK-801 (0.01-0.3
      mg/kg, i.p.) increased locomotor activity and rearing of intact rats. Bilateral 6
      OHDA+DMI lesion of the cACC caused greater reduction in the effect of MK-801 (0.1
      mg/kg) than that of the shell nucleus accumbens. These results suggest that
      increased extracellular DOPAC concentration (but not DA) and DOPAC/DA ratio in
      the cACC plays an important role in MK-801-hyperactivity.

PMID- 11829148
TI  - Protective effect of Salvia miltiorrhiza on angiotensin II-induced hypertrophic
      responses in neonatal rat cardiac cells.
AB  - The effect of the root of Salvia miltiorrhiza (SM) on angiotensin II (Ang II)
      induced hypertrophic responses was examined in cultured neonatal rat cardiac
      cells (cardiomyocytes and non-cardiomyocytes). The methanol eluate fraction (SM2)
      of the water extract and the ethyl acetate-insoluble fraction (SM3) and its
      soluble fraction (SM4) partitioned from the methanol extract were prepared.
      Treatment with SM4 (5-80 microg/ml), not SM2 and SM3, for 24 h produced dose
      dependent cytotoxicity against cardiac cells relative to the reduction in
      viability and the morphological injury of cardiomyocytes. SM2 or SM3 in the
      absence of Ang II affected neither hyperplastic nor hypertrophic growth of both
      cell types. However, SM3 (40 microg/ml) attenuated the positive chronotropic
      responsiveness of cardiomyocytes to Ang II (1 nM) stimulation, whereas Ang II
      induced increase in non-cardiomyocyte number was decreased only by SM2 (40
      microg/ml) treatment. Furthermore, SM3 suppressed Ang II-induced enlargement of
      cell size by preceding Ang II-induced induction of immediate early response gene
      (c-jun) expression in cardiomyocytes, while SM2 decreased Ang II-induced DNA
      synthesis in non-cardiomyocytes. Moreover, three phenolic compounds and
      tanshinone IIA that differed quantitatively among three SM fractions were
      identified by reverse-phase high performance liquid chromatography. Thus, the
      present findings indicate that the root of SM is an effective inhibitor of Ang II
      action and has a plural effective constituent, which possess different
      pharmacological activities on Ang II-induced hypertrophy and hyperplasia in
      cultured neonatal rat cardiac cells.

PMID- 11829149
TI  - Characteristics of learning and memory impairment induced by delta9
      tetrahydrocannabinol in rats.
AB  - We investigated the characteristics of delta9-tetrahydrocannabinol (THC)-induced
      impairment of learning and memory using an 8-arm radial maze task, a water maze,
      a visual discrimination task with 2 figures and a passive avoidance test in rats.
      THC (6 mg/kg, i.p.) impaired spatial memory in the standard task of the 8-arm
      radial maze. THC (4-6 mg/kg, i.p.) selectively impaired working memory in a
      reference and working memory task of the 8-arm radial maze. Even at a dose of 10
      mg/kg, THC did not impair spatial memory in the water maze. In addition, THC at a
      dose of 6 mg/kg, which had inhibitory effects in the 8-arm radial maze, did not
      affect performance in the visual discrimination task. These results indicate that
      at low doses (2-6 mg/kg), THC may not produce visual function abnormalities. THC
      impaired retrieval (6 mg/kg, i.p.) as well as acquisition (10 mg/kg, i.p.) in the
      passive avoidance test. The consolidation process was also impaired by i.c.v.
      injection (100 microg), but not i.p. injection (6-10 mg/kg) of THC. These results
      suggest that THC-induced impairment of spatial memory is based on the selective
      impairment of working memory through its effects on acquisition and retrieval
      processes.

PMID- 11829150
TI  - Origin of Ca2+ necessary for carbachol-induced contraction in longitudinal muscle
      of the proximal colon of rats.
AB  - The origin of Ca2+ necessary for carbachol (CCh)-induced contraction of
      longitudinal muscle of the proximal colon of rats was studied. CCh induced
      contraction of the muscle consisting of two phases, phasic and tonic phases, with
      a concomitant biphasic increase in [Ca2+]i. After removal of Ca2+ from the
      bathing solution of the colonic segments, CCh-induced contraction was rapidly
      inhibited; there was almost complete inhibition 1 min after the removal.
      Nicardipine, a blocker of voltage-dependent calcium channel, also significantly
      inhibited CCh-induced contraction. On the other hand, treatment of the colonic
      segments with thapsigargin, an inhibitor of sarcoplasmic reticulum (SR) Ca2+
      ATPase, did not significantly affect the contraction except causing a slight
      decrease in the rate of contraction. These results suggest that Ca> entering
      through voltage-dependent calcium channels, but not released from SR, is
      essential for CCh-induced contraction of longitudinal muscle of the proximal
      colon of rats. This strict dependency of the CCh-induced contraction on
      extracellular Ca2+ was discussed in relation to the results obtained in the
      fundus of rats.

PMID- 11829151
TI  - A potential role of bradykinin in angiogenesis and growth of S-180 mouse tumors.
AB  - Angiogenesis is an important event in tumor growth. We evaluated the contribution
      of endogenous bradykinin to tumor-associated angiogenesis and tumor growth using
      pharmacological approaches in mice bearing sarcoma 180 cells. The weight of
      implanted tumors increased in parallel with increased hemoglobin contents (a
      parameter to evaluate angiogenesis) over a 20-day experimental period. Daily
      administration of bradykinin B2-receptor antagonists, Hoe140 (0.1 and 1 mg/kg per
      day, local injection) or FR173657 (30 mg/kg per day, p.o.), significantly
      suppressed the increment in angiogenesis and tumor weight, but a B1-receptor
      antagonist, desArg10-Hoe140 (1 mg/kgperday), did not. Administration of a plasma
      kallikrein inhibitor, soybean trypsin inhibitor (3 mg/site per day),
      significantly suppressed angiogenesis and tumor growth. In contrast, bradykinin
      degrading enzyme inhibitors, captopril and phosphoramidon (500 microg/site per
      day), enhanced angiogenesis and increased tumor weight. Our results suggest that
      bradykinin, produced by plasma kallikrein or plasma kallikrein-like enzymes,
      promote tumor-associated angiogenesis and tumor growth in vivo.

PMID- 11829152
TI  - Addition of Maitake D-fraction reduces the effective dosage of vancomycin for the
      treatment of Listeria-infected mice.
AB  - Maitake D-fraction, beta1,6-glucan having beta1,3-branches, has been reported to
      activate the immune system of the host. To elucidate whether the D-fraction can
      reduce the clinical effective dosage of antibiotics in the treatment of
      opportunistic bacterial infection, we examined the effects of D-fraction on the
      treatment of Listeria monocytogenes-infected mice in combination with vancomycine
      (VCM), the only antibiotic used for methicillin-resistant Staphylococcus aureus
      (MRSA). Listeria-infection was introduced by its inoculation into the abdominal
      cavity of mice. Without treatment, all inoculated mice died within 3 days after
      the inoculation. In contrast, in the mice treated with combined therapy of D
      faction (10 mg/kg per day) and VCM (10 mg/kg per day), the survival rate was
      maintained at 60% on the 10th day after the inoculation, which was superior to
      that of mice treated with VCM alone (10 mg/kg per day). To investigate the
      mechanism underlying the reinforcement of VCM treatment by the D-fraction, the
      activities of macrophages and splenic T cells of Listeria-infected mice were
      evaluated. In mice administered with both D-fraction and VCM, macrophages
      produced 2.7 times as much interleukin-1 as that of non-treated control mice. The
      bactericidal activity of splenic T cells was also enhanced by 2.6 times of that
      of non-treated control mice. These results indicate that D-fraction activates
      immuno-competent cells, induced cytokine production, and consequently enhanced
      the bactericidal activities of the splenic T cells against Listeria
      monocytogenes, suggesting the clinical benefit of D-fraction in the case of anti
      bacterial treatment for patients with high risks.

PMID- 11829153
TI  - Effects of a kappa-receptor agonist U-50488 on bulbar respiratory neurons and its
      antagonistic action against the mu receptor-induced respiratory depression in
      decerebrate cats.
AB  - The function of kappa receptor-mechanisms in bulbar respiratory network was
      investigated in decerebrate cats. Intravenous injection of U-50488 (0.3-3.0
      mg/kg) dose-dependently decreased the phrenic nerve discharge and shortened
      inspiration and expiration. U-50488 caused hyperpolarization, and decreased input
      resistance and the action potential discharge in respiratory neurons. The effects
      of U-50488 were antagonized by nor-binaltorphimine. DAMGO (0.3 mg/kg, i.v.)
      decreased the phrenic discharge and prolonged inspiration and expiration. U-50488
      partially reversed the respiratory depression induced by DAMGO. These results
      suggest that the activation of K receptors by itself depresses the central
      respiratory activity, while it opposes the mu receptor-mediated respiratory
      depression.

PMID- 11829154
TI  - Protective effects of puerariaeflos against ethanol-induced apoptosis on human
      neuroblastoma cell line SK-N-MC.
AB  - Puerariaeflos (PF) is an oriental medical herb for alcohol abuse. To investigate
      whether PF possesses protective effects against ethanol (EtOH)-induced
      cytotoxicity in the central nervous system, 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide assay, flow cytometric analysis, DNA fragmentation
      assay, and reverse transcription-polymerase chain reaction were performed on SK-N
      MC human neuroblastoma cells. Cells treated with EtOH exhibited several apoptotic
      features, while those pre-treated with PF prior to EtOH exposure showed a
      decreased occurrence of apoptotic features. In addition, PF pre-treatment
      inhibited the EtOH-induced increase in caspase-3 mRNA expression. These results
      suggest that PF may exert protective effects against EtOH-induced apoptosis in
      human neuroblastoma cells.

PMID- 11829155
TI  - NMDA receptors in the spinal cord exert excitatory influences on spinal motor
      output in rats.
AB  - The role of NMDA receptors in the regulation of spinal motor output was studied
      in rats. Muscle tension of the hind limbs of decerebrate animals and spinal
      reflex potentials in anesthetized animals were recorded. Intrathecal injection as
      well as systemic or intra-4th ventricular injection of (+)-5-methyl-10-11-dihydro
      5H-dibenzo[a,d]cyclohepta-5-10-imine maleate (MK-801) reduced muscle tension.
      Systemic MK-801 did not alter monosynaptic reflexes either in intact or spinal
      rats, but attenuated polysynaptic reflexes in spinal rats. Thus spinal NMDA
      receptors participate in spinal motor output in the presence of some specific
      factors such as descending facilitation and preceding segmental depolarization,
      which remove the Mg2+ blocking.

PMID- 11829156
TI  - Rare but serious complications of acupuncture: traumatic lesions.
AB  - Acupuncture has a reputation among the public of being safe. Although recently
      performed prospective studies on the frequency of adverse effects of acupuncture
      found no severe complication, since 1965 many case reports of serious or even
      life-threatening incidents caused by acupuncture have appeared in the scientific
      literature. The most frequently reported complications are pneumothorax and
      lesions of the spinal cord. Severe injuries of peripheral nerves and blood
      vessels due to acupuncture seem to be very rare. Although case reports do not
      produce reliable data on the frequency of adverse events. information on sources
      of application errors can be extracted to increase the quality of acupuncture in
      education and therapy. All traumatic injuries described in this article could be
      avoided if practitioners had better anatomical knowledge, applied existing
      anatomical knowledge better, or both.

PMID- 11829157
TI  - Control of infection in acupuncture.
AB  - This paper is an update on infections, and potential infections, related to
      acupuncture, and a brief review of the relevant infection control procedures.
      There is no evidence at present to suggest that significant numbers of infections
      are being transmitted through standard acupuncture treatments in the UK. None the
      less, good infection control is essential. Like any other science, new research
      forces infection control to evolve and refine its procedures. Acupuncturists need
      to constantly review their standards as new viruses and risks are identified.

PMID- 11829158
TI  - Skin disinfection and acupuncture.
AB  - The need for skin disinfection before insertion of an acupuncture needle is
      controversial and there is no specific research on this topic. However research
      and observations on the effect of, and the need for, skin disinfection before
      injections forms a good analogy of acupuncture. Whilst micro-organisms present on
      the surface of the skin are accessible to disinfection, those located under the
      surface in ducts, glands and follicles are out of reach and can be inoculated
      into the sterile tissues below by needle insertion. Fortunately, the bacteria
      resident on the skin have a low potential to cause infection if host immunity is
      not severely impaired or compromised by the long-term presence of foreign
      material, such as a surgical stitch. Disinfection of clean skin before injection
      is not generally considered necessary and observations of lack of infection
      following injections without prior skin disinfection support this; however,
      contamination by micro-organisms not normally resident on skin can pose a higher
      risk of infection. If skin is visibly soiled, it should be washed and if needle
      insertion is near an infected or contaminated site, it should be disinfected with
      alcohol. Practitioner hand hygiene between patients is important, even if gloves
      are worn. Hands should be washed with soap or detergent and water, or an alcohol
      handrub can be used if hands are physically clean.

PMID- 11829159
TI  - Safety aspects of acupuncture in palliative care.
AB  - Acupuncture can mask symptoms of cancer and tumour progression. It is not safe to
      use such a therapy without full knowledge of the clinical stage of the disease,
      and the current status of orthodox therapy. Contraindications to acupuncture
      needling include an unstable spine, severe clotting disorder, neutropenia and
      lymphoedema. Whilst semi-permanent needles are used increasingly in symptom
      control and pain management they should not be used in patients with valvular
      heart disease or in vulnerable neutropenic patients. Acupuncture has an
      increasing role in support for pain and symptom management, but patients should
      not be advised to abandon conventional treatments in favour of complementary or
      alternative therapies alone, and should not have their hopes raised
      inappropriately, or have any guilt projected on to them for the cause of their
      cancer.

PMID- 11829160
TI  - Informed consent for acupuncture--an information leaflet developed by consensus.
AB  - Patients have the right to be fully informed about the likely benefits and risks
      of any proposed examination or treatment, and practitioners are obliged to obtain
      informed consent beforehand. Accurate information about the risks of acupuncture
      is available following publication of the results of two prospective surveys. At
      a joint meeting on the safety of acupuncture, members of the three largest UK
      professional bodies expressed a need to establish what information on risks
      patients should be given. A standard Information Leaflet was developed by
      consensus between thesc organisations, and is intended to be used as a stimulus
      for discussion of standard risks as well as any particular risks that might apply
      to individual patients. Additionally, it may be used as a form for written
      consent when this is required. To provide the context for using the Leaflet, the
      legal and ethical bases of informed consent for medical procedures are discussed.

PMID- 11829162
TI  - Adverse events associated with acupuncture reported in 2000.

PMID- 11829163
TI  - Risk information and informed consent in acupuncture--a proposal from Germany.

PMID- 11829164
TI  - Survey of adverse events following acupuncture (SAFA): a prospective study of
      32,000 consultations.
AB  - Acupuncture is increasingly used, so it is important to establish whether its
      benefits outweigh its risks. Numerous case reports of adverse events show that
      acupuncture is not free of risk, but accurate data from prospective
      investigations is scarce. A prospective survey was undertaken using intensive
      event monitoring. Forms were developed for reporting minor events each month and
      significant events as they occurred. The sample size was calculated to identify
      any adverse events that occurred more frequently than once in 10,000
      consultations. Acupuncturists were recruited from two professional organisations
      in the UK. Seventy-eight acupuncturists, all doctors or physiotherapists,
      reported a total of 2178 events occurring in 31,822 consultations, an incidence
      of 684 per 10,000 consultations. The most common minor adverse events were
      bleeding, needling pain, and aggravation of symptoms; aggravation was followed by
      resolution of symptoms in 70% of cases. There were 43 significant minor adverse
      events reported, a rate of 14 per 10,000, of which 13 (30%) interfered with daily
      activities. One patient suffered a seizure (probably reflex anoxic) during
      acupuncture, but no adverse event was classified as serious. Avoidable events
      included forgotten patients, needles left in patients, cellulitis and moxa burns.
      In conclusion, the incidence of adverse events following acupuncture performed by
      doctors and physiotherapists can be classified as minimal; some avoidable events
      do occur. Acupuncture seems, in skilled hands, one of the safer forms of medical
      intervention.

PMID- 11829165
TI  - A prospective survey of adverse events and treatment reactions following 34,000
      consultations with professional acupuncturists.
AB  - The paper describes the type and frequency of adverse events and transicnt
      reactions following consultations with professional acupuncturists. In a postal
      survey, involving 1,848 professional acupuncturists, all of whom were members of
      the British Acupuncture Council and practising in the UK, details of adverse
      events and transient reactions following treatment were recorded on standardised
      self-report forms. A sample size of 30,000 treatments was sought, and piloting
      indicated that a four-week period was required. Practitioners also provided
      information on themselves, including age, sex, length of training and years of
      practice. A total of 574 practitioners responded. 31% of the total population.
      These practitioners reported on adverse events and transient reactions associated
      with 34,407 treatments. No serious adverse events were reported, where these were
      defined as requiring hospital admission, prolonging hospital stays, permanently
      disabling, or resulting in death (95% CI: 0 to 1.1 per 10,000 treatments). A
      total of 43 significant minor adverse events were reported, a rate of 1.3 per
      1,000 treatments (95% CI: 0.9 to 1.7). These included severe nausea and actual
      fainting (12), unexpected, severe and prolonged aggravation of symptoms (7),
      prolonged and unacceptable pain and bruising (5) and psychological and emotional
      reactions (4). There were three avoidable events: two patients had needles left
      in by mistake, and one patient had moxa burns to the skin, also caused by
      practitioner error. The acupuncturists also recorded 10,920 mild transient
      reactions occurring in 5136 treatments. 15% (95% CI: 14.6 to 15.3) of the 34,407
      total. In terms of local reactions, there were reports of mild bruising (1.7%),
      pain (1.2%) and bleeding (0.4%). Practitioners reported that patients experienced
      an aggravation of existing symptoms after 2.8% of treatments. The most common
      mild transient reactions to treatment were feeling relaxed (11.9%) and feeling
      energised (6.6%). In this prospective survey of 34,407 treatments, practitioners
      reported no serious adverse events. This conclusion was based on data collected
      from one in three members of the British Acupuncture Council. Given that the
      whole membership delivers between one and a half and two million treatments a
      year, this is important evidence on public health and safety. When compared with
      medication routinely prescribed in primary care, the results suggest that
      acupuncture is a relatively safe treatment modality.

PMID- 11829166
TI  - Development of the equine brain motor system.
AB  - The purpose of the present study was to demonstrate the structural maturation of
      the horse brain in the critical period of development emergence of coordinated
      locomotion. Equine brains from 14 days before expected birth to adulthood were
      fixed in formaldehyde and embedded in paraffin. After taking the outer parameters
      of the brains, full series of large-area coronal sections were prepared on a
      special microtome and stained with Nissl's cresyl violet and Haidenhain's iron
      haematoxylin. Microscopic images of sections were digitized and were subjected to
      computer-aided image analysis. The gross morphology of the brains and the image
      analysis of histological preparations suggest that in the perinatal period
      studied there is no substantial increase in brain size and mass, while the amount
      of Nissl substance and myelin grows rapidly till postnatal day 45. Then a
      relative decrease of both is observed till adulthood accompanied by a doubling of
      brain size and mass. It is concluded that during the maturation of the equine
      brain, decisive changes of the motor system such as up-regulation of protein
      sysnthesis and full myelination of motor tracts takes place during the critical
      period of onset of coordinated locomotion.

PMID- 11829167
TI  - Respiratory responses to electrical stimulation of the basal ganglia in cats.
AB  - The aim of the present study was to investigate the involvement of basal ganglia
      in altering respiration. The experiments were carried out on cats using the
      electrical stimulation techniques. The electrical stimulation of the basal
      ganglia caused locus-dependent changes both in the tidal volume and the rate of
      respiration. The most frequent effect of stimulation was hyperpnea and decrease
      in the tidal volume in awake, freely moving cats. An increase in the tidal volume
      appeared only as rebound-like aftereffect. The stimulation that caused hyperpnea
      in awake cats elicited smaller changes under chloralose or ketamine-induced
      anaesthesia, and, in certain cases, the stimulation produced apnea. After locally
      applied neurotoxic damage, the electrical stimulation failed to induce
      significant respiratory changes. It is suggested that the fast, small amplitude
      ventilation is, probably, produced by high excitation that shifts the respiratory
      rhythm generator towards the upper limits of its regulatory range. The slowing of
      ventilation might be produced by an inhibitory mechanism, which is able to cause
      even apnea under anaesthesia.

PMID- 11829168
TI  - The role of the mamillary body in the propagation of the ictal activity.
AB  - To determine the importance of fornix and mamillary body atrophy in the secondary
      generalization of the complex partial seizures fornix and mamillary bodies of 11
      hippocampal sclerosis patients with secondary generalization (SG) and 3 without
      secondary generalization (WSG) were retrospectively evaluated using MRI images.
      Small fornix and/or mamillary body was not found in WSG group. In SG group the
      frequencies of small fornix and mamillary body were 64% and 45%, respectively,
      all being ipsilateral to sclerotic side. The frequency of small fornix in the SG
      group was statistically higher than WSG group (p<0.01). All small mamillary
      bodies were accompanied by ipsilateral small fornices. Considering the spatially
      decreasing frequency and the ipsilaterality of the hippocampal sclerosis,
      forniceal atrophy and mamillary body atrophy, a temporo-spatial relationship of
      the above-stated structures that may link focal seizures to secondary
      generalization was postulated.

PMID- 11829169
TI  - Post-embedding double-gold labeling immunoelectron microscopic co-localization of
      neurotransmitters in the rat brain.
AB  - In this report, we describe a new quantitative electron microscopic protocol
      based on the use of double colloidal-gold post-embedding immunostaining procedure
      as markers to analyze the subcellular distribution of enkephalin (ENK) and GABA
      neurotransmitters simultaneously in the same ultrathin tissue sections in the
      periaqueductal gray area (PAG) of the rat brain. Double-gold particle signals
      were significantly improved using a number of technical adjustments for the
      immunogold electron microscopic co-localization technique of ENK and GABA. The
      GABA-like neuronal elements were immuno-reacted with 20 nm gold particles and the
      enkephalin-like immunoreactive neurons were labeled with 10 nm gold particles.
      This double labeling was more apparent in tissue sections that were deactivated
      for the gold staining of the first antibody. Excellent double labeling was
      obtained when we blocked antigenicity of the first antiserum with hot (80 degrees
      C) paraformaldehyde fumes. To minimize the clumping of the second gold particles
      around the first gold particles used against the first antibody, we tried
      different staining order for the neurotransmitters tested in this study. It was
      necessary to use a detergent (Triton X-100) at very low concentration (0.1%)
      instead of etching to expose the antigenic determinants of the neurotransmitters
      and at the same time to reduce the deleterious effects on the morphology of the
      tissue sections. Furthermore, the high-glutaraldehyde fixation and the decrease
      in the interval between cutting and labeling of the ultrathin sections
      significantly improved the results obtained in this study. Double labeling of
      sections with ENK and GABA produced co-localization in 23.1% and 1.2% of the
      immunoreactive axonal terminals and dendrites, respectively. Most of the double
      labeled terminals contained more GABA-like than ENK-like immunolabeling. Half of
      the axon terminals [51%] and dendrites [56%] in the ventrolateral PAG were not
      labeled with either of GABA or ENK immunoreactivity. This procedure was found to
      be completely compatible with good double immunolabeling and ultrastructural
      preservation.

PMID- 11829170
TI  - On the front line.

PMID- 11829171
TI  - What is your Diagnosis? Alopecia areata of the eyelashes.

PMID- 11829172
TI  - What's eating you? Centruroides exilicauda.

PMID- 11829173
TI  - Maffucci syndrome: a case report.
AB  - The multiple enchondromas and hemangiomas of Maffucci syndrome affect the skin
      and skeletal systems. The disease develops slowly, with enlargement of
      enchondromas and hemangiomas occurring during the first 2 decades of life.
      Effects of the disease range from those requiring minor adjustments in activities
      of daily living to almost total incapacitation.

PMID- 11829174
TI  - Eyelid pilomatricomas in young adults: a report of 8 cases.
AB  - Pilomatricomas are common benign childhood tumors, which usually occur in the
      head and neck region. We present 8 patients and review the clinical and
      histopathologic features of pilomatricoma of the eyelids and eyebrows in young
      adults. From 1992 to 2000, diagnosis of eyelid pilomatricoma was performed in 8
      young adults (13-36 years). The female-male ratio was 3:1. The mean age at
      presentation was 22 years. Each of our 8 patients had a single tumor, 4 on the
      upper eyelid and 4 on the eyebrow. Ossification existed in 4 cases. No tumor
      recurrence has been noted at 3.9 years. Pilomatricomas are uncommon tumors on the
      eyelid and brow region of young adults. These lesions are frequently misdiagnosed
      when evaluation is based on clinical evidence alone: only 4 of our cases were
      correctly diagnosed prior to excisional biopsy.

PMID- 11829175
TI  - Cutaneous anthrax: a concise review.
AB  - With the growing threat of bioterrorism, it has become important for clinicians
      to recognize the clinical manifestations of diseases spread in this manner. The
      aim of this article is to provide readers with a complete and detailed
      understanding of anthrax, with a specific concentration on the cutaneous
      manifestations and a concentrated review of the treatment and current information
      known about Bacillus anthracis.

PMID- 11829176
TI  - An eruption secondary to intravenous immunoglobulin therapy.
AB  - A 42-year-old woman presented with a recurrent eruption over the distal
      extremities. Lesions formed a few days after initiation of intravenous
      immunoglobulin (IVIg) therapy and lasted 2 to 3 weeks after therapy completion.
      Results of a histologic examination revealed parakeratosis, exocytosis, and
      spongiosis. The clinical and histologic findings are similar to previous reports.
      The mechanism of this eruption is not known.

PMID- 11829177
TI  - Plasma cell gingivitis.
AB  - Plasma cell gingivitis (PCG), an infrequent benign inflammatory condition of
      unknown etiology, is a type of plasma cell orificial mucositis, which includes a
      wide spectrum of conditions. We present the case of a 13-year-old girl who had
      PCG with an erythematous congestive plaque on the anterior maxillary gingiva for
      4 years. Occasionally, the lesion became increasingly swollen and painful and
      bled. Results of a histopathologic examination showed dense plasmacytic
      infiltrate in the dermis, affecting the dermoepidermal border, with
      immunohistochemical positivity in the K and A light chains and vascular
      proliferation. "Lozenge" keratinocytes, "watery" spongiosis, and exocytosis were
      seen in the epidermis. Laboratory analysis showed notably low levels of both
      serum IgA and secretory IgA. We consider whether secretory IgA at low levels has
      an important etiopathogenic role favoring the development of localized
      subclinical repetitive infections that could lead to chronic PCG.

PMID- 11829178
TI  - Coexistent infections on a child's distal phalanx: blistering dactylitis and
      herpetic whitlow.
AB  - We report a case of coexistent Staphylococcus aureus and herpes simplex virus
      (HSV) infections responsible for a bullous and vesicular eruption on a child's
      distal phalanx. Blistering distal dactylitis (BDD), a superficial infection of
      the distal portion of the finger, is seen most commonly in children and is caused
      by either beta-hemolytic streptococci or S aureus. Herpetic whitlow, also a
      blistering infection found on children's distal fingers, is a bacteriologic
      sterile infection caused by HSV-1 or HSV-2. In this report, we note that these
      infections may coexist on the distal phalanx. This case has implications for
      diagnosis and treatment of children's blistering hand diseases.

PMID- 11829179
TI  - Urticaria associated with a small cell carcinoma of the lung.
AB  - Urticaria has been observed occasionally in association with lymphoproliferative
      disorders. We report the case of a 56-year-old man with acute urticaria
      associated with a small cell carcinoma of the lung. Following surgical treatment,
      the patient remained free of the urticaria.

PMID- 11829180
TI  - Angiokeratoma of Fordyce as a cause of red scrotum.
AB  - Two men presented with asymptomatic diffuse redness of the scrotum. Examination
      showed angiokeratoma of Fordyce (AF), an associated finding. In our practice, AF
      and diffuse scrotal redness co-occur in 50% of patients. Providing reassurance to
      the patient is appropriate if this clinical link is detected.

PMID- 11829181
TI  - Hereditary pincer nail.
AB  - Pincer nail is a rare dystrophy characterized by transverse overcurvature that
      increases distally along the longitudinal axis of the nail. Etiology,
      pathogenesis, and inheritance of this dystrophy are not clear. We report on 3
      remotely consanguineous siblings (2 girls, 1 boy) with pincer nail of the toes.
      Case distribution in this family raises the possibility of autosomal-recessive
      mendelian inheritance.

PMID- 11829182
TI  - Periungual myxoid neurofibroma.
AB  - A 34-year-old woman presented with a slow growing nontender nodule on her left
      index finger that had been present for 2 years. The tumor was excised and was
      histologically determined to be a myxoid neurofibroma. We report this case
      because of the rarity of both the tumor and its periungual location and to
      provide a review of the literature.

PMID- 11829183
TI  - Shadow cell basal cell carcinoma with acantholysis.
AB  - I present histologic documentation of a unique basal cell carcinoma (BCC) in
      which shadow cells formed the major cellular component along with extensive
      acantholysis and the development of ringed shadow cells. This neoplasm contained
      trichohyalin granules, which are indisputable evidence of follicular
      differentiation. Shadow cells rarely are encountered within BCCs and generally
      form relatively small components. Such neoplasms have been labeled BCC with
      matrical differentiation. Because of nonspecificity and ambiguity, I propose that
      this terminology be abandoned and replaced by shadow cell BCC.

PMID- 11829184
TI  - Perianal ulcerations from topical steroid use.
AB  - Topical steroids play an extremely important role in the treatment of various
      dermatologic conditions. Use of topical steroids must be approached with caution,
      however, as they can have serious side effects. We report a case of iatrogenic
      perianal ulcers caused by twice-daily application of Lotrisone (clotrimazole and
      betamethasone dipropionate) in the perianal region. High-potency topical steroids
      should be used sparingly and briefly in intertriginous areas.

PMID- 11829186
TI  - "Early" vocal cord laterofixation for the treatment of bilateral vocal cord
      immobility.
AB  - OBJECTIVES: Vocal cord immobility (VCI) is commonly caused by a nonlaryngeal
      malignancy, thyroid surgery, or a presumed viral insult etc. The paralysis is
      often transient or temporary, thus the care of the patient should be optimized to
      avoid unnecessary diagnostic and therapeutic endeavours. This article reports on
      the result of the concept of early vocal cord laterofixation, which provides a
      minimally invasive solution to dyspnea in the critical early, potentially
      reversible, period of bilateral VCI. STUDY DESIGN: A prospective study of 25
      consecutive patients (ages 33 to 81 years) who were diagnosed with a bilateral
      VCI. This condition had developed after thyroid surgery in 22 of the patients and
      after a blunt trauma of the neck in one case. In another case, a cricoarytenoid
      joint fixation was revealed, and aetiology remained unknown in one further
      patient. METHODS: The surgical procedure was performed endoscopically with a
      modification of Lichtenberger's endo-extralaryngeal suture lateralization
      technique. The abducted vocal cord position was achieved by inserting a non
      resorbable thread around the vocal process and tying on to the prelaryngeal
      muscles. Regular spirometric measurements and radiological aspiration tests were
      conducted on the patients. RESULTS: Adequate postoperative airway was achieved in
      all patients except one. Significant spontaneous vocal cord medialization was
      observed in two cases within a year and in three patients in the second and the
      third year. Partial or complete vocal cord recovery was observed in 17 cases.
      Further voice improvement followed in 9 patients when the threads were removed,
      due to vocal cord medialization or recovery. The mild postoperative aspirations
      ceased in the first postoperative days in all cases except one. CONCLUSIONS: The
      concept of "early" laterofixation satisfies the important criteria: it can
      provide an immediate and long-lasting adequate airway, and it can be considered
      potentially reversible from the point of view of laryngeal functions. Thus the
      procedure is a reliable primary treatment for bilateral VCI.

PMID- 11829185
TI  - Comparison of perceptional nasal obstruction with rhinomanometric and acoustic
      rhinometric assessment.
AB  - Perception of nasal stuffiness, together with rhinomanometric and acoustic
      rhinometric assessments were evaluated before and after nasal and/or sinus
      surgery in 50 Japanese adult patients. Nasal resistance on both expiration and
      inspiration correlated well with the patients' perceptions (P<0.05). Nasal
      volumes (0-4 cm and 0-7 cm) obtained from acoustic rhinometry measurements also
      correlated well with perception (P<0.05). No significant relationships were found
      between rhinomanometric and acoustic rhinometric results. Perceptional nasal
      obstruction, rhinomanometric and acoustic rhinometric results (except for the
      sectional areas at the I-notch) improved significantly after the operations.
      Rhinomanometry and acoustic rhinometry are valuable methods for assessing nasal
      stuffiness, but we must take account of the differences between the two methods.

PMID- 11829187
TI  - Investigating quality of life and coping resources after laryngectomy.
AB  - Surgical procedures and in particular laryngectomy can become a life-saving
      treatment for patients with laryngeal or hypopharyngeal cancer, but can result in
      permanent damage. Clinical observation suggests that patients vary considerably
      in their ways of dealing with this new situation and in their ability to cope.
      The aim of our interdisciplinary group was to investigate the quality of life of
      laryngectomy patients and learn about their perceptions, situation and coping
      mechanisms. The development of an appropriate study design and a measurement
      strategy is presented. We investigated 29 laryngectomized patients who had joined
      the local self-help group. The patients were free from tumour disease and were
      mostly married with children, retired from work and had not graduated from high
      school. Assessment of the quality of life was performed with the European
      Organization for Research on Treatment of Cancer questionnaires QLQ-C30 and H+N35
      and additional open questions. Analysis of the acquired data showed that family
      support was judged most important for overcoming the problems of disease and
      treatment. Deficits in this area were highly correlated with a low overall
      quality of life. Financial problems resulted because of the high percentage of
      retirement before or after therapy. We suggest that perioperative support taking
      these facts into consideration can result in an improved coping process. Further
      prospective studies are needed to reveal the effect of such measures.

PMID- 11829188
TI  - Influence of noise exposure on antioxidant system and TEOAEs in rabbits.
AB  - Noise exposure may cause hearing loss. The precise mechanism leading to cochlear
      damage in aco trauma is not known. Eight rabbits were used in this study.
      Transient evoked otoacoustic emissions (TEOAEs) were recorded in all animals and
      blood malondialdehyde (MDA) and glutathione (GSH) levels were determined. All
      rabbits were then exposed to 100 dB SPL broadband noise for 1 h. TEOAEs were
      recorded again and blood MDA and GSH levels determined following noise exposure.
      The reproducibility scores of the TEOAE measurements were found to be
      significantly lower (P < 0.01), whereas the amplitudes and signal-to-noise values
      of emissions decreased (P > 0.01) in rabbits exposed to noise. The TEOAE energies
      were poor at 4 kHz. During this threshold shift, GSH blood levels decreased and
      MDA levels increased,indicating that there is a close relationship between noise
      induced hearing loss and the antioxidant system. These findings indicate that
      TEOAE recording is an excellent test for detecting effects of noise on hearing.

PMID- 11829189
TI  - Nonlinear digital hearing aid with near-instantaneous amplitude compression.
AB  - We designed a new type of nonlinear digital hearing aid (TD-1) with near
      instantaneous amplitude compression for sensorineural hearing-impaired people.
      The amplification method utilized by the TD-1 normalizes the signal waveforms
      within a time window bounded by two adjacent positive going zero-crossing points.
      The signals within this window are amplified so that the maximum amplitude
      reaches a preset value, thus allowing a consistent peak amplitude to be
      maintained. To test this, we examined the efficacy of the TD-1 device in 31
      patients with sensorineural hearing loss. When tested for recognition of Japanese
      sentences in a quiet environment, 7 of 25 (28.0%) subjects wearing the TD-1
      showed a 20% or greater increase in the maximum intelligibility score than that
      obtained when wearing their own linear hearing aids. In addition, 7 of 31 (22.6%)
      subjects showed the same increase with the TD-1 relative to that obtained when
      they wore HA70 or HA73 devices (Rion Co., Ltd., Tokyo, Japan), which are
      conventional analogue hearing aids. These results indicate that TD-1 can be
      effective for patients with sensorineural hearing loss.

PMID- 11829190
TI  - The effect of chronic otitis media on the immunoreactivity of human inner ear.
AB  - Twenty temporal bones (TBs) were removed from autopsy cases and prepared for
      immunohistochemical examination. Ten TBs were free of ear disease whereas the
      other ten TBs showed the signs of chronic otitis media. Expression of markers for
      monocyte-macrophages (25F9, 27E10) and natural killer cells (anti-Leu-11) was
      examined immunohistochemically. There were no specific positive stainings with
      25F9 or anti-Leu-11 antibodies in any of the specimens. Staining for 27E10 was
      found to be negative in each section obtained from normal cochlea. However, 27E10
      positivity was detected in three of ten TBs with signs of chronic ear
      inflammation. This positivity can be explained by two theories: (1) activated
      monocytes can enter the inner ear from the systemic circulation as a consequence
      of chronic antigen challenge; (2) mesothelial cells could become activated as a
      result of a cross-reaction, with resultant positivity. Development of
      sensorineural hearing loss in some cases of chronic otitis media may be due to
      these immunological reactions.

PMID- 11829191
TI  - External versus endoscopic approach in the surgical treatment of glottic cancer.
AB  - Laryngeal carcinomas in the early stages of evolution can be treated by different
      therapies. In this paper we present our personal experience with T1 and small T2
      laryngeal glottic cancer treated by conventional surgery and by endoscopic laser
      surgery. In the period 1983-1997, we saw 573 patients affected by T1 and limited
      T2 glottic tumours. In particular, we treated 325 case of T1a tumour, 185 T1b and
      63 T2 (ventricle floor). As regards surgical techniques, we employed cordectomy
      by laryngofissure in 196 patients; laser cordectomy in 129 cases; widened laser
      cordectomy in 63 cases; fronto-lateral laryngectomies according to Leroux-Robert
      in 110 patients; laser cordo-commissurectomies in 37 cases; horizontal
      glottectomies according to Calearo-Teatini in 9 cases, and laser glottectomies in
      29 patients. The average oncological results, considered for every stage and
      every surgical technique were 84.4% (484 cancers definitively controlled by
      primary surgery). For comparison of oncological and clinical results, we
      evaluated patients affected by tumours with similar extension that had been
      treated by different surgical techniques. Oncological results were similar in the
      two groups. In the group treated by laser surgery we found a shorter clinical
      course and the best possibility of salvage therapy in the case of local
      recurrence.

PMID- 11829192
TI  - Prognostic value of the expression of p53 and bcl-2 in patients with laryngeal
      carcinoma.
AB  - Previous studies have yielded inconsistent results on the prognostic significance
      of p53 and bcl-2 in head and neck cancer. The aim of this study was the
      evaluation of p53 and bcl-2 protein expression in laryngeal squamous cell
      carcinoma and to clarify the relationship between them. All patients with
      laryngeal carcinoma were treated during the period 1991-1993. In the present
      study p53 and bcl-2 expression in paraffin sections from 50 cases of laryngeal
      squamous cell carcinoma were analysed and correlated with routine clinico
      pathological parameters. The expressions of p53 and bcl-2 were examined by
      immunohistochemical staining. Immunoreactivity for p53 was observed in 45 (90%)
      of carcinomas and bcl-2 immunoreactivity in 7 (14%). No significant correlation
      between the p53 or bcl-2 expression and patients' T- or N-stage, histological
      grading, or overall survival was found.

PMID- 11829193
TI  - Pectoralis major myocutaneous flap: analysis of complications in difficult
      patients.
AB  - The purpose of this study was to assess and discuss the effects of old age and
      systemic diseases on complications related to the use of a pectoralis major
      myocutaneous flap (PMMF) for reconstruction in head and neck surgery. Eighty-four
      consecutive patients, operated on between January 1992 and December 1998, were
      included in the study. Of these patients, 47 were in relatively good condition,
      while 37were old and frail or affected by systemic diseases. Patients were
      monitored for complications during a follow-up of 2 years. All patients included
      in the study had very advanced squamous cell carcinomas (T3-T4) and
      reconstruction with PMMF was performed after a commando procedure, a total
      laryngectomy with partial pharyngectomy, or a composite resection. Necrosis of
      skin island was the most frequently encountered complication, but no surgical
      intervention was needed. Overall, complications occurred more frequently in
      patients with underlying pathologies, the risk ratio adjusted for age and sex
      being 2.94, but 95% confidence intervals were 0.99-8.65 and all complications
      were minor. In summary, we recommend the use of PMMF for immediate repair in
      difficult patients who have large oropharyngo-laryngeal excisions and radical
      neck dissections and who suffer concomitantly with various medical problems known
      to increase complication rates. PMMF proved to be suitable to give these patients
      good chances of a quick recovery with satisfactory aesthetic and functional
      results.

PMID- 11829194
TI  - Subjective functional results 1 year after surgery and postoperative radiation
      for oropharyngeal carcinoma.
AB  - This study was conducted to find out what factors most influenced functional
      results and patient satisfaction at 1 year after treatment in a homogeneous group
      of patients who had undergone surgery and postoperative radiotherapy for the
      treatment of oropharyngeal carcinoma. Further aims were to find out the relation
      between the overall and specific disease-related results and to compare the two
      questionnaires used. The study group consisted of 102 patients, 23 women and 79
      men, with an age range of 41-77 years (mean 45.7 years). Two questionnaires were
      used for evaluation. The University of Washington head and neck quality of life
      questionnaire (UW-QOL) includes information about nine disease-specific domains
      and three questions on general quality of life. The second questionnaire used was
      the performance status scale for head and neck cancer patients (PSS), containing
      information about three disease-specific domains. Functional results were
      influenced by the size of tumor and by the surgical method used. Results worsened
      with increasing T stage. The best results were found after pharyngotomy without
      mandibulotomy, worse results, following temporary mandibulotomy with
      osteosynthesis, and the poorest results were found in the group of patients who
      had undergone composite resection. Neither age and sex of the patients nor the
      course of healing influenced the functional results. All results were
      significantly correlated to one another. The general parameters were also closely
      related to specific domains. An important correlation was found between the
      parameters in the two questionnaires.

PMID- 11829195
TI  - Abnormal elevation of resting pressure at the upper esophageal sphincter of
      Parkinson's disease patients.
AB  - We investigated the oral and pharyngeal swallowing function in seven Parkinson's
      disease (PD) patients, using videomanofluorometry, which is videofluorographic
      and manometric evaluation conducted simultaneously. Abnormal elevations of
      resting pressure were found at the upper esophageal sphincter (UES) in three of
      the seven cases, when they were asked to hold a bolus in the mouth and initiate
      swallowing. One of these three cases showed an abnormal elevation of resting
      pressure, intermingled with a normal pressure pattern. Since the UES showed
      complete relaxation in these three cases, it is inappropriate to suppose that
      irreversible pathophysiological changes at the level of peripheral nerves had
      occurred. Our results suggested that altered resting pressure resulted from
      dysfunction at a more central level, such as a lack of dopaminergic stimulation
      at the supramedullary level causing skeletal muscle rigidity. Since a tonic
      abnormality of the UES cannot be measured by only videofluorography, both
      videofluorographic and manometric evaluation will be necessary to assess the
      pharyngeal phase of swallowing in PD patients.

PMID- 11829196
TI  - Intracochlea acoustic neuroma: a case report and discussion.
AB  - A case of an intracochlea acoustic neuroma that was diagnosed radiologically is
      presented and discussed.

PMID- 11829197
TI  - Efficacy of therapeutic drug monitoring in prevention of hypoglycemia caused by
      cibenzoline.
AB  - OBJECTIVE: The purpose of this study was to evaluate the efficacy of our
      therapeutic drug monitoring (TDM) services in cibenzoline therapy using the risk
      of hypoglycemia as an end point. METHODS: The TDM services of cibenzoline were
      introduced in March 1998. If the serum concentrations of cibenzoline deviated
      from the therapeutic range, adjustment of dosage was recommended. In addition,
      the physicians were recommended to pay attention to the hypoglycemia induced by
      cibenzoline. A series of case-control studies were performed before and after
      introduction of TDM services. After introduction of TDM services of cibenzoline,
      four case-control studies were performed every 6 months between March 1998 and
      February 2000 (stage 2 between March 1998 and August 1998; stage 3 between
      September 1998 and February 1999; stage 4 between March 1999 and August 1999;
      stage 5 between September 1999 and February 2000) using the same method as in the
      previous study which had been performed between September 1997 and February 1998
      (stage 1). The TDM data of inpatients and outpatients between March 1998 and
      February 2000 were reviewed. RESULTS: A significantly increased risk of
      hypoglycemia was observed for users of cibenzoline during stage 1 [crude odds
      ratio (OR) 10.4; 95% confidence interval (CI) 2.7-40.3], stage 2 (crude OR 3.1;
      95% CI 1.0-9.0), and stage 3 (crude OR 3.8; 95% CI 1.2-12.7). However, during
      stage 4 and stage 5, no significantly increased risk of hypoglycemia was
      observed. There was no significant difference between the mean doses during stage
      1 and stage 5. However, there was a significant difference in the distributions
      of the trough levels among the four stages. During stage 4 and stage 5, the
      percentage of samples with a trough level of 200-400 ng/ml was higher than during
      stage 2 and stage 3. During stage 2, the percentage of samples with a trough
      level over 400 ng/ml was 42.9%. Furthermore, the risk of hypoglycemia associated
      with cibenzoline use decreased together with the increase in the percentage of
      outpatients whose serum concentrations of cibenzoline had been measured in the
      past. The risk of hypoglycemia associated with cibenzoline use decreased after
      introduction of TDM of cibenzoline. CONCLUSION: Dose adjustment based on TDM and
      the physicians' increased recognition of hypoglycemia associated with cibenzoline
      use were beneficial for those patients treated with cibenzoline in order to
      prevent hypoglycemia.

PMID- 11829198
TI  - Local effect of transdermal isosorbide dinitrate ointment on hand vein diameter.
AB  - OBJECTIVE: To assess the effect of topically applied isosorbide dinitrate (ISDN)
      ointment on superficial hand veins preconstricted with phenylephrine. METHODS:
      Using the hand vein compliance technique, venous diameter changes were measured
      in a double-blind, randomised, placebo-controlled cross-over trial in 12 healthy
      volunteers. During preconstriction with phenylephrine, placebo or ISDN ointment
      was administered to assess the dilator effect of transdermal ISDN. Finally a
      single i.v. dose of nitroglycerine was administered into the hand vein to assess
      the maximal venous response to organic nitrovasodilators. RESULTS: ISDN ointment
      (equivalent to 13.4 +/- 3.61 mg ISDN) caused a significant dilator effect of 39.1
      +/- 21.7% (mean +/- SEM, P=0.02) which reached its maximum after 42.5 +/- 16.6
      min. Maximum ISDN effects were inversely correlated with venous baseline diameter
      (r2=0.38, P=0.03) and independent of the amount of ointment applied or the extent
      of preconstriction (P > 0.3). CONCLUSION: Similar to nitroglycerine, topical ISDN
      may relax superficial hand veins within 60 min after application, suggesting that
      it might ease venepuncture particularly of small vessels. The large variability
      of the effect and the time to reach the effect, however, restrict its practical
      usefulness.

PMID- 11829199
TI  - Effect of influenza vaccination on serum clozapine and its main metabolite
      concentrations in patients with schizophrenia.
AB  - OBJECTIVE: To study the effect of influenza vaccine on serum clozapine, N
      desmethylclozapine and clozapine-N-oxide steady-state concentrations in patients
      with schizophrenia. METHODS: This was an open-label study in 14 schizophrenic
      inpatients (with 2 drop-outs) using clozapine. Serum trough concentrations of
      clozapine. N-desmethylclozapine and clozapine-N-oxide, as well as the
      concentration of c-reactive protein (CRP), were measured immediately before
      conventional trivalent influenza vaccination and 2, 4, 7 and 14 days after the
      vaccination. RESULTS: Influenza vaccination had no significant effect on serum
      concentrations of clozapine, N-desmethylclozapine or clozapine-N-oxide. No
      changes in the clinical effects of clozapine were observed after vaccination.
      Influenza vaccination did not increase CRP. However, two drop-out patients who
      developed upper respiratory and abdominal symptoms had increased and elevated
      serum concentrations of clozapine, compared with the baseline. CONCLUSIONS:
      Influenza vaccination using conventional trivalent influenza vaccine does not
      affect serum concentrations of clozapine or its main metabolites. However, an
      infection-related increase in CRP may be associated with increased serum
      concentration of clozapine.

PMID- 11829201
TI  - The prevalence of CYP2D6 and CYP2C19 genotypes in a population of healthy Dutch
      volunteers.
AB  - AIM: This study was performed in a sample of the Dutch population to estimate the
      prevalence of noncoding mutations of CYP2D6 and CYP2C19 as obtained by
      genotyping. In addition, the predictability of the genotyping strategy was
      assessed. METHODS: The CYP2D6 and CYP2C19 status of 765 unrelated healthy
      volunteers was evaluated. Dextromethorphan and mephenytoin were used for
      determining the phenotypes. Genotyping was performed by PCR on the most common
      null alleles for CYP2D6 (except for CYP2D6*5) and CYP2C19. RESULTS: For CYP2D6,
      the most frequently observed null allele was CYP2D6*4, which accounted for 89% of
      all null alleles. The prevalence of poor metabolizers (PMs) in healthy volunteers
      was 5.5%, which was lower than that found previously by phenotyping (8.0%; chi2
      test P = 0.009). For CYP2C19*2 and CYP2C19*3, the frequencies were 13.3% and
      0.2%, respectively. The S:R ratio was significantly higher in heterozygous
      subjects (S:R ratio 0.22) than in homozygous wild type subjects (S:R ratio 0.11).
      Comparison of all subjects below 45 years showed a significantly higher S:R ratio
      in the female ones compared to the male ones, especially in heterozygous subjects
      (S:R ratio 0.39 vs. 0. 19; P < 0.001). CONCLUSIONS: The frequencies of CYP2D6 and
      CYP2C19 allelic variants were in accordance with other European populations.
      Assessment of *3, *4, *6, *7, and *8 alleles for CYP2D6, and *2 and *3 for
      CYP2C19, predicted the phenotype with an accuracy of over 98.6%. A gene-dose
      effect was found for CYP2C19. CYP2C19 heterozygous female subjects had a
      decreased CYP2C19 activity that may be at least partly due to the use of oral
      contraceptives.

PMID- 11829202
TI  - Population pharmacokinetics of fluconazole given for secondary prevention of
      oropharyngeal candidiasis in HIV-positive patients.
AB  - OBJECTIVES: To determine fluconazole population pharmacokinetics and explore the
      relationships between fluconazole average concentration and treatment
      effectiveness or microbiological resistance induction during a study aimed at
      evaluating the efficacy, tolerability and resistance induction after secondary
      prevention with fluconazole (150 mg weekly) versus placebo in human
      immunodeficiency virus-positive (HIV+) patients with oropharyngeal candidiasis.
      METHODS: Population pharmacokinetic parameters of fluconazole determined from 458
      serum drug concentration measurements obtained over 37 months in 132 HIV +
      patients not receiving highly active antiretroviral therapy. Mean estimates and
      variabilities were generated using non-linear regression analysis. Logistic and
      linear regression analyses were used to explore the relationships between the
      estimated average concentration of fluconazole and candidiasis relapse or fungal
      resistance towards fluconazole. RESULTS: Fluconazole kinetics were best described
      by a one-compartment model with first-order oral absorp tion from the
      gastrointestinal tract. The pharmacokinetics were influenced only by body weight.
      No effect was observed for gender, age, height or lymphocyte CD4 counts. The mean
      apparent population clearance was 0.79 l/h, the volume of distribution 571 and
      the absorption constant (ka) 0.93 h(-1). Inter-occasion variability in clearance
      (45%) was large relative to intersubject variability (21%). Taking into account
      the average fluconazole concentration or the time above the minimal inhibitory
      concentrations did not clinically improve the prediction of the occurrence of
      oropharyngeal relapse or microbiological resistance. CONCLUSION: The relationship
      between fluconazole concentrations and preventive effectiveness was poor.
      Together with the rather large inter-occasion variability in fluconazole
      clearance, this suggests no role of therapeutic drug monitoring in optimising
      fluconazole treatment for secondary prevention.

PMID- 11829200
TI  - Role of CYP3A4 and CYP2C19 in the stereoselective metabolism of lansoprazole by
      human liver microsomes.
AB  - OBJECTIVE: The aim of this investigation was to clarify the stereoselective
      properties in lansoprazole metabolism by monitoring the metabolic consumption for
      each enantiomer and the formation of the main metabolites, lansoprazole sulfone
      and 5-hydroxylansoprazole, in the presence of human liver microsomal enzymes.
      METHODS: Human liver microsomes or recombinant cytochrome P450 (CYP) enzymes were
      incubated with either (+/- )-, (+)-, or (-)-lansoprazole in the presence of
      reduced nicotinamide adenine dinucleotide phosphate. The metabolic consumption of
      lansoprazole enantiomers was estimated from the amounts of enantiomers consumed
      by microsomal enzymes after incubation at 37 degrees C for 60 min. Metabolites of
      lansoprazole, lansoprazole sulfone, and 5-hydroxylansoprazole were determined
      after incubation at 37 degrees C for 20 min, and kinetic parameters [Michaelis
      constant (Km) and maximum velocity (Vmax)] were obtained using Eadie-Hofstee
      plots. RESULTS: (-)-Lansoprazole was metabolized more preferentially than (+)
      lansoprazole in human liver microsomes. Stereoselective sulfoxidation and
      hydroxylation [(+) > (-)] were observed in human liver microsomes. Strikingly, in
      sulfoxidation, a significantly higher intrinsic clearance (Vmax,l/Km,l) of (-)
      lansoprazole (0.023 +/- 0.001 ml/min/mg) than (+)-lansoprazole (0.006 +/- 0.000
      ml/min/mg) was observed. Consequently, sulfoxidation is likely to play an
      important role in the stereoselective metabolism of lansoprazole enantiomers.
      P450-isoform specificity for each enantiomer was evident. CYP3A4, which mainly
      catalyzed sulfoxidation, was more active toward (-)-lansoprazole in either a
      chiral or racemic drug as a substrate. CYP2C19, which catalyzed hydroxylation,
      preferentially metabolized (+)-lansoprazole. The consumption of (+)-lansoprazole
      was markedly inhibited by (-)-lansoprazole, indicating a metabolic
      enantiomer/enantiomer interaction. However, this alteration of recombinant
      CYP2C19 specificity for (+)-lansoprazole did not appear in metabolism in human
      liver microsomes. CONCLUSIONS: Stereoselective metabolism was observed in human
      liver microsomes, and this stereoselectivity was mainly based on CYP3A4
      specificity for preferable metabolism of (-)-lansoprazole.

PMID- 11829203
TI  - The role of CYP2C9 genotype in the metabolism of diclofenac in vivo and in vitro.
AB  - INTRODUCTION: The polymorphic cytochrome P450 enzyme 2C9 (CYP2C9) catalyses the
      metabolism of many drugs including S-warfarin, acenocoumarol, phenytoin,
      tolbutamide, losartan and most of the non-steroidal anti-inflammatory drugs.
      Diclofenac is metabolised to 4'-hydroxy (OH), the major diclofenac metabolite, 3'
      OH and 3'-OH-4'-methoxy metabolites by CYP2C9. The aim of the present study was
      to clarify the impact of the CYP2C9 polymorphism on the metabolism of diclofenac
      both in vivo and in vitro. SUBJECTS, MATERIALS AND METHODS: Twenty healthy
      volunteers with different CYP2C9 genotypes [i.e. CYP2C9*1/ *1 (n = 6), *1/*2 (n =
      3), *1,/*3 (n = 5), *2/*3 (n = 4), *21*2 (n = 1), *31*3 (n = 1)] received a
      single 50-mg oral dose of diclofenac. Plasma pharmacokinetics [peak plasma
      concentration (Cmax), half-life (t 1/2) and area under the plasma concentration
      time curve (AUCtotal)] and urinary recovery of diclofenac and its metabolites
      were compared between the genotypes. Diclofenac 4'-hydroxylation was also
      analysed in vitro in 16 different samples of genotyped [i.e. CYP2C9*1/*1 (n = 7),
      *1/*2 (n=2), *1/*3 (n = 2), *2/*3 (n = 2), *2/*2 (n = 2), *31/*3 (n = 1)] human
      liver microsomes. RESULTS: Within each genotype group, a high variability was
      observed in kinetic parameters for diclofenac and 4'-OH-diclofenac (6- and 20
      fold, respectively). No significant differences were found between the different
      genotypes either in vivo or in human liver microsomes. No correlation was found
      between the plasma AUC ratio of diclofenac/4'-OH-diclofenac and that of losartan/
      E-3174, previously determined in the same subjects. CONCLUSION: No relationship
      was found between the CYP2C9 genotype and the 4'-hydroxylation of diclofenac
      either in vivo or in vitro. This, together with the lack of correlation between
      losartan oxidation and diclofenac hydroxylation in vivo raises the question about
      the usefulness of diclofenac as a CYP2C9 probe.

PMID- 11829204
TI  - Non-steroidal anti-inflammatory and cytoprotective drug co-prescription in
      general practice. A general practitioner-based survey in France.
AB  - BACKGROUND AND AIM: Non-steroidal anti-inflammatory drugs (NSAIDs) represent one
      of the most frequently prescribed drugs. Gastrointestinal damage, the most common
      side effect of NSAIDs. can be limited by the prescription of cytoprotective
      agents. In order to assess determinants of NSAID-associated cytoprotective agent
      prescriptions in primary care practice, we performed a general practitioner (GP)
      based study. METHODS: After a 2-month intensive information campaign, the
      participation of all GPs of the Cote d'Or (France) administrative area was
      requested. During a 2-month period, GPs had to return a mailed questionnaire on
      NSAID prescription for up to ten consecutive patients aged over 18 years who
      required NSAIDs. This 30-item questionnaire included questions about the patient,
      the type of NSAID and the GP. RESULTS: GP participation rate was 24%, and 791
      prescriptions were provided. GPs who participated in the study were
      representative of GPs of the area in terms of sex, time elapsed since graduation
      and GP practice area. Around 80% of the patients included in the study were under
      the age of 65 years. The proportion of prescriptions combining NSAIDs and
      gastroprotective agents was 29.5%. Omeprazole accounted for 58% of the
      coprescriptions and misoprostol for 29%. Independent determinants associated with
      the co-prescription of a cytoprotective agent were age [odds ratio (OR) 4.1;
      confidence interval (CI) 95% 2.3 7.4], previous history of poor NSAID tolerance
      (OR 10.4; CI 95% 5.8-18.6), previous history of moderate to severe digestive
      disorders (OR 13.4; CI 95% 5.1 35.4) and indication for chronic illness (OR 1.8,
      CI 95% 1.1-3.1). Prescriptions of cytoprotective drugs were in conformity with
      official guidelines for 78.3% of the patients. Although around 60% of the
      patients with risk factors for poor tolerance received a gastroprotective drug,
      50% of the patients over 65 years did not receive it. Conversely, nearly 12% of
      the patients with no risk factors were prescribed cytoprotective agents. Patient
      history was the main reason put forward by GPs for prescribing cytoprotective
      drugs. CONCLUSION: Although a large majority of GP prescriptions were in
      accordance with official recommendations, inadequate NSAID prescription practices
      remain relatively frequent especially with regard to the elderly.

PMID- 11829205
TI  - Dynamic regulation of EEG power and coherence is lost early and globally in
      probable DAT.
AB  - Electroencephalographic (EEG) findings in dementia of Alzheimer type (DAT)
      include slowing of alpha frequency, loss of alpha band power, increased theta and
      delta power and reduced coherence. Here it is evaluated whether a) EEG
      acquisition during different functional states facilitates the detection of DAT
      associated EEG changes, and b) EEG changes in mild DAT are topographically
      confined or global. Power spectra and coherence of EEGs from 29 patients with
      mild probable DAT and 28 age- and sex-matched controls were compared during three
      cognitive states. Group differences in power spectra and coherence were largest
      during resting with eyes open, yielding a 77% correct classification result.
      Already in early stages of probable DAT, EEG changes were topographically wide
      spread. The task-related up- and down-regulation of power and coherence was
      impaired already in mild probable DAT. We propose to augment clinical EEG
      assessment by including a quantitative analysis of the dynamic power and
      coherence changes from rest, eyes closed to eyes open in suspected DAT.

PMID- 11829206
TI  - Basic parameters of saccadic eye movements--differences between unmedicated
      schizophrenia and affective disorder patients.
AB  - BACKGROUND: Smooth pursuit eye movement (SPEM) dysfunctions are considered a
      biological marker for schizophrenia and have been studied widely. In contrast,
      saccadic eye movements have received less attention, although disturbances have
      been described previously. Basic neurophysiologic parameters of saccades in
      schizophrenics, especially in unmedicated patients, have not been studied
      extensively. METHODS: Saccadic eye movements of 38 unmedicated schizophrenic
      patients, 32 patients with major depression and 42 non-psychiatric controls were
      examined using high-resolution infrared oculography. Two large-amplitude saccadic
      tasks were presented. The groups were compared on peak velocity, reaction time
      and accuracy. RESULTS: Peak velocity was significantly increased in schizophrenic
      patients. Depressive patients had a significantly longer reaction time. Both
      patient groups needed more corrective saccades to reach the target than controls.
      CONCLUSIONS: Peak velocity distinguishes unmedicated schizophrenic patients from
      depressive patients and normal controls. This could be explained by deficits of
      the prefrontal cortex in the inhibitory control of saccades. Our findings suggest
      that schizophrenia affects not only SPEM but also saccadic eye movements.

PMID- 11829207
TI  - Relationship between exploratory eye movements and clinical course in
      schizophrenic patients.
AB  - Exploratory eye movements are psychophysiological indicators of schizophrenia as
      well as smooth pursuit eye movements. To investigate whether these eye movements
      change in accordance with the clinical course of the condition in schizophrenia,
      exploratory eye movements (number of eye fixations, mean eye scanning length,
      responsive search score, evaluation of reproduced Fig. 1 and 2) of 28
      schizophrenic patients were evaluated in repeat test design, conducted an average
      of 8 months apart. Subjects were first-medicated schizophrenics, half were
      outpatients and the remaining half were inpatients at the Neuropsychiatry ward of
      Tokyo Medical and Dental University Hospital. Exploratory eye movement patterns
      did not improve despite an improvement in clinical symptoms of schizophrenia.
      This result and those of previous studies of the exploratory eye movements of
      schizophrenic patients' families suggest that exploratory eye movements reflect a
      schizophrenic vulnerability marker. Furthermore, decreased mean eye scanning
      length (MESL) values were observed in subjects who showed unimproved symptoms,
      particularly negative symptoms over an extended period of time. The result
      suggests that a decrease in the MESL value may be the most sensitive indicator in
      the development of chronicity in schizophrenia.

PMID- 11829208
TI  - Amisulpride: efficacy in the management of chronic patients with predominant
      negative symptoms of schizophrenia.
AB  - Amisulpride is a dopamine D2/D3-selective antipsychotic drug with potent
      antipsychotic efficacy in acute exacerbations of schizophrenia. It also possesses
      substantial efficacy in chronic schizophrenic patients with enduring predominant
      negative symptoms. This unique property has been demonstrated in a series of
      short (6 weeks) and medium-/long-term (6-12 months) double-blind placebo
      controlled studies. The patients in these studies were carefully selected and
      assessed to avoid confounding results with non-specific changes in other symptom
      domains. The results not only show effects on negative symptoms at the optimal
      dose of 100 mg/day, but also significant improvement in global functioning. The
      effect observed in short-term studies was maintained over longer treatment
      periods (6-12 months). Amisulpride was well tolerated with a safety profile
      similar to placebo. These results open a new therapeutic approach for negative
      symptoms, one of the most disabling aspects of schizophrenia.

PMID- 11829209
TI  - Frontotemporal dementia: clinical, neuroimaging, and molecular biological
      findings in 6 patients.
AB  - Establishing the diagnosis in patients with clinical signs and symptoms
      suggesting primary degenerative disease with marked frontal lobe involvement is
      difficult. Neuroimaging methods, in particular positron emission tomography (PET)
      with the tracer 18fluoro-2-deoxyglucose (FDG) and cerebrospinal fluid (CSF)
      examination of beta-amyloid and tau-protein levels may give additional
      information. We report five patients with clinical and radiological features of
      degenerative dementia with predominantly frontal involvement and one patient with
      primary progressive aphasia Diagnostic work-up included computed tomography (CT),
      magnetic resonance imaging (MRI), PET and tau-protein and beta-amyloid level
      determination in CSF. While neuropsychological performance varied among patients,
      CT and MRI demonstrated persistently frontal lobe involvement. PET revealed
      corresponding changes with frontal hypometabolism, but in addition, four patients
      (among them two with no corresponding temporal changes in CT or MRI) showed a
      decreased glucose uptake in the temporal cortices. CSF samples from five patients
      revealed elevated beta-amyloid 1-42 and tau levels in three and two patients,
      respectively. Reduced beta-amyloid 1-40 was found in two patients. We conclude
      that occurrence of clinical symptoms of frontotemporal dementia is accompanied by
      frontal hypometabolism regardless of additional clinical findings. The value of
      determination of beta-amyloid and tau protein levels remains to be determined.

PMID- 11829210
TI  - Psychopathology in dual diagnosis and non-addicted schizophrenics--are there
      differences?
AB  - In a previous publication we reported lifetime and 3-month prevalence estimates
      for substance use in two large samples of schizophrenic inpatients (Soyka et al.
      1993). A subsequent analysis of psychopathological findings assessed by means of
      the AMDP Manual (Guy and Ban 1982) in schizophrenic in-patients of the Haar
      Mental State Hospital (N=447), in whom a lifetime prevalence for substance use of
      42.9% (3-month prevalence 29%) had been reported, was performed. While the
      overall differences between substance using (dual diagnosis) and nonusing
      schizophrenics were small, dual diagnosis patients in general reported more
      positive symptoms, especially more intense hallucinations. These differences
      could basically be demonstrated in patients with current (3-month) substance use
      on admission but not on discharge possibly as a result of substance use. Most
      marked and highly significant results were found with respect to previous suicide
      attempts and delinquency which were more prevalent in dual diagnosis
      schizophrenics. Results of this study indicate that dual diagnosis patients
      compared to other schizophrenics represent a more disturbed patient group.
      Implications for the self-medication hypothesis for substance use in
      schizophrenia and future research in this area are discussed.

PMID- 11829211
TI  - Are needs and satisfaction of care associated with quality of life? An
      epidemiological survey among the severely mentally ill in the Netherlands.
AB  - Is the quality of life of severe mentally ill patients influenced by the
      intensity of the care provided, their satisfaction with services and/or the
      amount of unmet needs? The interrelatedness of these three outcome measures was
      investigated in a sample of 101 patients dependent on long-term psychiatric care
      in the Northeast of the Netherlands. Instruments used were the Camberwell
      Assessment of Needs, the Verona Service Satisfaction Schedule and a health
      related quality of life instrument, the EuroQoL. Quality of life was unrelated to
      satisfaction with services but was strongly associated with unmet needs in the
      area of mental and physical health, and of rehabilitation. Quality of life
      decreased as needs increased. Needs were also strongly related to diagnosis and
      cognitive functioning. Furthermore, more intensive care settings were provided as
      needs increased. Demographic, diagnostic and treatment variables did not explain
      much extra variance in quality of life. Despite the availability of various
      services in the region there was a lack of tailor made care which took into
      account specific unmet needs with regard to information, social contacts, and
      daily activities.

PMID- 11829212
TI  - Changes in aortic rotational flow during cardiopulmonary bypass studied by
      transesophageal echocardiography and magnetic resonance velocity imaging: a
      potential mechanism for atheroembolism during cardiopulmonary bypass.
AB  - The human aorta is a curved conduit with a complex three-dimensional geometry.
      The curvature influences axial velocity distribution and introduces transverse
      velocity components. Rotational flow in the aorta can be demonstrated during
      normal pulsatile flow using transesophageal echocardiography. Cardiopulmonary
      bypass may affect the pattern of rotational flow in the aorta and thus influence
      the generation of atheroemboli. We investigated rotational flow in the descending
      aorta using color flow mapping and pulse-wave Doppler on transesophageal
      echocardiography before and during cardiopulmonary bypass. We correlated our
      findings with magnetic resonance velocity imaging in a model of a human aortic
      arch connected to a cardiopulmonary bypass circuit. Before cardiopulmonary
      bypass, rotational flow in the descending aorta was seen in 37 of 40 patients
      (93%). In the majority of these patients, rotational flow was in the clockwise
      direction during systole, looking in the direction of flow (30 of 37 patients,
      81%, P < 0.01 vs counterclockwise rotation). During cardiopulmonary bypass, there
      were almost equal numbers of patients with clockwise (18 patients) and
      counterclockwise rotation (19 patients). Forty-seven percent of patients with
      clockwise rotation before cardiopulmonary bypass developed reversal in the
      direction of rotation to counterclockwise during cardiopulmonary bypass. Twenty
      nine percent of patients with counterclockwise rotation developed reversal of the
      direction of rotation during cardiopulmonary bypass. The transverse velocity
      component increased during cardiopulmonary bypass regardless of the direction of
      rotation. We also demonstrated clockwise rotation in the descending aorta of a
      human aortic arch model connected to a cardiopulmonary bypass circuit using
      magnetic resonance velocity mapping. Before cardiopulmonary bypass, rotation was
      predominantly clockwise, while during cardiopulmonary bypass, there was no
      preferred direction of rotation. The geometry of the aorta, which is fairly
      constant in all patients, imposes handedness to aortic flow before
      cardiopulmonary bypass. However, during cardiopulmonary bypass, other extrinsic
      factors such as aortic cannula orientation may influence the direction of
      rotation. The change in direction of rotational flow and increase in its
      transverse velocity component during cardiopulmonary bypass may have implications
      for atheroembolism and arterial branch perfusion during extended periods of non
      pulsatile flow.

PMID- 11829213
TI  - Inhibition of nitric oxide synthesis increases apoptotic cardiomyocyte death and
      myocardial angiotensin-converting enzyme gene expression in ischemia/reperfusion
      injured myocardium of rats.
AB  - Cardiomyocyte apoptosis is an important pathogenic mechanism in myocardial
      ischemia/reperfusion (I/R) injury. It has been shown that nitric oxide (NO) and
      the renin-angiotensin system (RAS) are closely related, and both systems regulate
      apoptotic cell death. However, the effects of NO modulation on myocardial
      apoptotic cell death and changes in the RAS in the I/R-injured myocardium have
      not been studied. Female Sprague-Dawley rats were randomized into three groups:
      NO synthesis inhibitor, N(G)-nitro-L-arginine-methyl ester (L-NAME, 10mg/kg); NO
      precursor, L-arginine (540mg/kg); and vehicle. The rats were then subjected to 45
      min coronary occlusion followed by 4 h reperfusion. The TdT-mediated in situ nick
      and labeling (TUNEL) indices were 39.9%+/-0.8% at the border and 30.9%+/-1.2% at
      the center of the I/R area in the vehicle group. L-NAME administration
      significantly increased these TUNEL-positive cells to 45.3%+/-1.9% and 37.9%+/
      1.3%, respectively (P < 0.05 each). L-arginine administration reduced the TUNEL
      index at the border zone with marginal significance (P = 0.08 vs vehicle group).
      I/R injury significantly reduced the angiotensin-converting enzyme (ACE) mRNA
      expression in the left (ventricular) free wall of vehicle group rats. However,
      ACE mRNA expression was 1.9 times greater in the L-NAME group than that in the
      vehicle group (P < 0.05). This study showed that the inhibition of NO synthesis
      increased apoptotic cardiomyocyte death and local ACE mRNA expression in the I/R
      injured myocardium. Our observations indicate that NO, ACE, and apoptotic
      cardiomyocyte death are related to each other during I/R injury.

PMID- 11829214
TI  - Restoration of patency after apparent occlusion of the lambda-graft's right
      branch.
AB  - The "string sign" is a physiological and reversible response of the internal
      mammary artery (IMA) anastomosed to a moderately stenotic coronary artery. We
      describe a patient who presented postoperatively with a string sign phenomenon of
      the right branch of the lambda-composite graft. The graft regained full patency
      32 months after the surgical procedure with progression of the native coronary
      artery stenotic lesion. This case demonstrates that under specific conditions,
      such as the progression of native coronary artery disease, a no-flow composite
      graft employing IMAs can only regain patency and functional status in the same
      way as in situ IMAs. These findings confirm that the IMA remains the conduit of
      choice not only for its long-term patency, but also for its physiological
      adaptation characteristics.

PMID- 11829215
TI  - Takayasu arteritis with multiple cardiovascular complications.
AB  - A 60-year-old Japanese woman first presented in 1990 with effort angina. She
      underwent coronary angiography and was diagnosed with bilateral coronary ostial
      stenosis and Takayasu arteritis. Coronary artery bypass graft surgery (CABG) for
      multiple vessels was attempted, but the blood flow in the bilateral internal
      thoracic and gastroepiploic arteries was to poor for a donor artery, and the
      calcification of the ascending aortic wall was too severe for anastomosis of
      saphenous vein grafts. Therefore, the proper hepatic artery was connected to the
      left anterior descending artery using a vein graft. In April 2000, the patient's
      angina worsened. Occlusions of both subclavian arteries, bilateral coronary
      ostial stenosis and vein graft occlusion, aortic valve regurgitation, and two
      severe stenoses of the descending aorta were observed. Aortic valve replacement,
      and coronary and aorta revascularization were desirable, but the severe aortic
      wall calcification and thickening rendered these interventions impossible.
      Treatment with medication was chosen. The patient was discharged without severe
      angina. A combination of these serious cardiovascular complications which do not
      allow any surgical intervention is very rare.

PMID- 11829217
TI  - Coronary residuals of Kawasaki's disease in an elderly man.

PMID- 11829216
TI  - Acute myocarditis with transient eosinophilia and serum hyper-IgE-emia in a
      patient with atopic dermatitis.
AB  - A 14-year-old girl with acute myocarditis, transient eosinophilia, and hyper-IgE
      emia associated with atopic dermatitis is described. The patient was admitted
      because of severe heart failure and shock, and severe atopic dermatitis was seen.
      Blood examinations showed moderate eosinophilia (1917/mm3) and hyper-IgE-emia
      (830IU/ml). The response to treatment with dopamine was excellent, and the
      congestive heart failure was gradually ameliorated, followed by improvement in
      her atopic dermatitis. In addition, rapid improvement in eosinophilia and hyper
      IgE-emia was observed. Histopathological examination of the right ventricular
      myocardium obtained by endomyocardial biopsy showed mild interstitial fibrosis
      and mild infiltrations of inflammatory cells, indicating myocarditis. We
      speculated that the transient eosinophilia and hyper-IgE-emia in the present case
      indicated that an allergen induced strong allergic reactions, including type 1
      allergy, and caused both acute myocarditis and deterioration of the atopic
      dermatitis; specifically noteworthy is that the patient's disease rapidly
      improved without corticosteroid treatment.

PMID- 11829218
TI  - Incidental tumor attached to the aortic valve.

PMID- 11829219
TI  - Initial experience with off-pump coronary artery bypass grafting.
AB  - Off-pump coronary artery bypass grafting (OPCAB) is clearly preferable for
      patients with extracardiac complications. The aim of this study was to evaluate
      the initial outcome of OPCAB, and its validity for patients with extracardiac
      complications. One hundred and fifty-seven consecutive coronary artery bypass
      graft (CABG) patients were divided into two groups: 30 OPCAB patients and 127 on
      pump CABG patients. The early outcomes of the two groups were compared.
      Preoperatively, OPCAB patients had more extracardiac risk factors than on-pump
      CABG patients. There were no differences in age or cardiac function between the
      groups, but the off-pump group had a higher incidence of previous surgery,
      cerebrovascular disease, and renal failure. There were no differences in graft
      patency, stroke, or mortality between the two groups, even though the OPCAB
      patients had more risk factors than the on-pump patients. Our initial experience
      with OPCAB showed that it is acceptable for high-risk patients in view of the
      serious nature of their extracardiac condition.

PMID- 11829220
TI  - Four acute confusion assessment instruments: reliability and validity for use in
      long-term care facilities.
AB  - Frail older adults in long-term care (LTC) facilities are at high risk for acute
      confusion. This study evaluated the reliability and validity of four acute
      confusion instruments for use in LTC: the Clinical Assessment of Confusion-A (CAC
      A), the Clinical Assessment of Confusion-B (CAC-B), the NEECHAM Confusion Scale
      (NEECHAM), and the Visual Analog Scale for Acute Confusion (VASAC). Seventy-four
      residents from two LTC facilities were evaluated for acute confusion using the
      four instruments as well as the Mini-Mental Status Examination (MMSE), the
      Geriatric Depression Scale (GDS), and Diagnostic and Statistical Manual for
      Mental Disorders (DSM IV) criteria for delirium. Coefficient alphas were .82 for
      the CAC-A, .86 for the CAC-B, and .80 for the NEECHAM. Interrater reliability on
      30 paired evaluations was .90 for the CAC-B, .87 for the NEECHAM, and .80 for the
      VAS-AC. All instruments were correlated with the MMSE and the DSM IV criteria for
      delirium at the p < .001 level. Predictive validity was supported for the CAC-B,
      the NEECHAM, and the VAS-AC. Discriminant validity using the GDS was supported
      for the VAS-AC. Construct validity using confirmatory factor analysis was
      supported for the NEECHAM, with a two-factor structure. Based on this study, the
      VAS-AC is recommended for use as a general screening instrument and when it is
      positive for acute confusion, the NEECHAM should be used for a more indepth
      assessment.

PMID- 11829221
TI  - Chronic pain: challenges and assessment strategies.
AB  - Older adults are a rapidly growing segment of the world population, and long-term
      care will continue to be a major concern for most health care institutions in
      this century. Pain management remains at the forefront of long-term care issues,
      with older patients more subject than younger patients to chronic disease states
      that predispose them to pain. Assessment and management of chronic pain, however,
      are impeded by a lack of patient and caregiver education regarding pain,
      widespread misconceptions about pain in older patients, and special concerns and
      cautions for appropriate analgesic use in this population. This is the first of a
      two-part series highlighting issues and strategies related to pain assessment in
      older adults.

PMID- 11829222
TI  - Pacing of activity as a predictor of agitation for persons with dementia in acute
      care.

PMID- 11829223
TI  - APNs in ALFs.

PMID- 11829224
TI  - A comparison of African American & Caucasian American female caregivers of rural,
      post-stroke, bedbound older adults.
AB  - As changes in health care take place, the care of older adults in the home
      becomes a greater responsibility of informal caregivers. The purpose of this
      study was to compare African American and Caucasian American female caregivers of
      post-stroke, bedbound older adults in rural Mississippi. A purposive sample of 74
      caregivers reported bedbound older adults' functional impairments, along with
      caregivers' stress and self-efficacy, social support, coping, depression, and
      life satisfaction. Significant differences were determined for self-efficacy
      between the African American and Caucasian American caregivers. Disordinal
      interactions existed between race and caregiving self-efficacy on the variables
      of stress and life satisfaction. Nurses must be cognizant of the many stressors
      influenced by cultural factors, such as race, faced by these caregivers. This is
      important to include in the curricula of nursing programs for the 21st century.

PMID- 11829225
TI  - Creating a continuum of care for elderly individuals.

PMID- 11829226
TI  - Assisted living: strategies for initiating an advanced practice nurse clinic.

PMID- 11829227
TI  - Mandibular reconstruction with prefabricated vascularized bone grafts using
      recombinant human osteogenic protein-1: an experimental study in miniature pigs.
      Part II: transplantation.
AB  - Osteogenic Protein-1 (rhOP-1), also called bone morphogenetic protein-7 (BMP-7),
      is osteoinductive. The aim of this study was to present a new surgical technique:
      the prefabrication of a vascularized bone graft using rhOP-1 and its
      microsurgical transplantation. During 6 weeks, osteomuscular grafts were
      prefabricated in the latissimus dorsi muscle of five adult minipigs. Six hundred
      micrograms rhOP-1 on a carrier of xenogenic bone mineral in block form were used.
      The grafts were transplanted into defects of the mandibular angles performing a
      microsurgical anastomosis and using miniplates for fixation. Identical defects of
      the contralateral side were treated by direct application of 600 microg rhOP-1
      and xenogenic bone mineral. A polychrome sequential labelling was applied. After
      transplantation the bone stayed viable, demonstrated by continuous apposition of
      fluorochromes (non-decalcified histologic sections) and bone scintigraphy. The
      reconstructive result was significantly superior in the prefabrication technique,
      assessed by histology and computerized tomography (CT). In conclusion, the method
      has a potential to become a clinical alternative for conventional vascularized
      bone grafts.

PMID- 11829228
TI  - Long-term results following surgical treatment of benign symmetric lipomatosis
      (BSL).
AB  - Benign symmetric lipomatosis is a rare disease. Its main characteristic is the
      symmetric deposition of fat, in an unencapsulated form, at typical sites in the
      body, but primarily in the head and neck region. Its aetiopathogenesis is
      unknown. A disturbance of lipid metabolism is involved, and there is a proven
      connection with chronic alcoholism. Problems with the differential diagnosis of
      the characteristic clinical picture arise from the fact that this disease is not
      widely recognized. Over a period of 30 years, the authors treated 31 patients
      with benign symmetric lipomatosis. They review the pertinent literature and
      report retrospectively on the fates of the 11 surviving patients.

PMID- 11829229
TI  - Novel methods for quantifying soft tissue changes after orthognathic surgery.
AB  - Laser scanners are becoming increasingly important as a tool for quantifying the
      outcome of facial surgery. However, few computer algorithms have been developed
      for this purpose. Researchers have either measured the differences in the
      positions of (manually located) landmarks, or have taken radial measurements of
      the distances between surfaces. Neither of these techniques provides satisfactory
      information about the shape changes between surfaces. In this paper, alternative
      methods are proposed and their performance is compared with that of the radial
      method. Tests on two patients show that the Correspondences by Sensitivity to
      Movement (CSM) and closest point algorithms provide the most realistic
      measurements of the differences between two surfaces. The CSM method was found to
      be useful for pinpointing areas where the shape has changed.

PMID- 11829230
TI  - Plate fixation after mandibular osteotomy.
AB  - Skeletal asymmetry in patients who undergo orthognathic surgery is frequently
      associated with postoperative temporomandibular joint (TMJ) disorders caused by
      condylar rotation. This study was designed to elucidate the relation between
      changes in the condylar long axis and TMJ function after bisagittal split
      osteotomy (BSSO). A total of 42 patients with mandibular prognathism underwent
      BSSO. Split osseous fragments were secured by standard titanium plates in 22
      patients; bent titanium plates were used to secure fragments in 20 patients. The
      angle of the bent plates was adjusted to avoid displacement of the condyle after
      osteotomy, as compared with condylar position on preoperative submental-vertical
      (S-V) cephalograms. The postoperative position of the condyle was assessed on X
      ray film, and changes in TMJ function were evaluated. The condylar long axis
      differed significantly on X-ray film between patients using a standard titanium
      plate and those using a bent plate (P<0.05), and no sign of TMJ functional
      impairment was noted in the bent-plate group. Although the use of bent plates
      requires further study, maintenance of a suitable position of the condyle
      relative to the condylar axis is one of the conditions for a successful outcome
      of BSSO.

PMID- 11829231
TI  - The Mitek mini anchor for TMJ disc repositioning: surgical technique and results.
AB  - This study evaluated our treatment outcomes in 105 patients (188 discs) using the
      Mitek mini anchor for temporomandibular joint (TMJ) articular disc repositioning
      surgery, with 88 patients having simultaneous orthognathic surgery. Criteria for
      inclusion into the study were: (1) Presurgical TMJ disc displacement with
      salvageable disc; (2) No prior TMJ surgery; (3) TMJ disc repositioning with the
      Mitek mini anchor; (4) Absence of connective tissue/autoimmune disease; (5)
      Absence of postsurgical trauma; and (6) Minimum of 12 months postsurgery follow
      up. Presurgery (T1), immediately postsurgery (T2), and longest follow up (LFU)
      clinical and radiographic evaluations were performed. The mean age of the
      patients was 32.6 years (range 14-57 years), and mean follow-up time was 46.2
      months (range 14-84 months). Radiographic evaluation at LFU demonstrated no
      significant condylar resorption or positional changes of the anchors. At LFU,
      there was a statistically significant reduction in: TMJ pain, facial pain,
      headaches, TMJ noises and disability, and improvement in jaw function and diet.
      Maximum incisal opening improved slightly and lateral excursive movements
      decreased slightly. The Mitek mini anchor provides a predictable method for
      stabilizing the TMJ articular disc to the condyle and a high success rate in
      decreasing TMJ dysfunction and pain in patients with no previous TMJ surgery.

PMID- 11829232
TI  - Treatment of squamous cell carcinoma of the lip using Foscan-mediated
      photodynamic therapy.
AB  - Carcinoma of the lip is a common cancer of the head and neck area; its incidence
      is approximately one-quarter that for oral cavity cancers. It occurs most
      frequently on the lower lip of elderly males. This non-randomized Phase II study
      aimed to estimate the complete response (CR) rate to Foscan-mediated photodynamic
      therapy (Foscan-PDT) in patients with primary cancer of the lip, duration of CR,
      and the tolerability and safety of Foscan-PDT. Twenty-five patients with squamous
      cell carcinoma (SCC) of the lip (Tis, T1, T2/N0/M0) and Karnofsky status > or =
      70 received 0.15 mg/kg Foscan intravenously, followed 4 days later by a single
      non-thermal illumination of the tumour (light dose 20 J/cm2, irradiance 100
      mW/cm2, lambda=652 nm). Response was determined after 12 weeks and mean follow up
      is 424 days so far. After 12 weeks, 96% of cases (24/25) showed CR, and all CRs
      were confirmed by biopsy. The most common adverse event was swelling and local
      pain at the treatment site. Tumour recurrence was observed in two patients 4 and
      18 months after PDT. One patient developed a single lymph node metastasis 7
      months after therapy. Photosensitivity reactions occurred in five patients. The
      functional results were excellent in all patients without any signs of limited
      mouth opening or impaired lip closure. The cosmetic outcome was better than after
      surgical therapy. Foscan-PDT is an effective treatment modality for small primary
      tumours of the lips. Foscan-PDT yields complete response rates comparable to
      those published for surgery or radiotherapy without causing major toxicity. It
      allows preservation of form and function and does not compromise future treatment
      options for recurrent, residual or second primary disease.

PMID- 11829233
TI  - Alveolar ridge augmentation by distraction osteogenesis.
AB  - Distraction osteogenesis is an alternative method for reconstructing atrophic
      alveolar bone. Fourteen patients underwent vertical alveolar distraction by the
      LEAD SYSTEM-Endosseous Alveolar Distraction System (Stryker Leibinger, Kalamazoo,
      MI). An alveolar segmental osteotomy was carried out and the vertical distraction
      device was mounted. In patients with an extensive alveolar defect, two
      distraction devices were placed in order to better control the vector of
      elongation in both bone edges. The distraction was started on the fourth
      postoperative day at a rate of 0.8 mm/day for 10-16 days, followed by a
      consolidation period of 60 days. Vertical distraction osteogenesis (VDO) was
      completed successfully in all patients with segment lengths in the range of 8 to
      13 mm and with an average of 10.3 mm. Subsequently, the devices were removed and
      23 threaded titanium dental implants were placed for osteointegration. Earlier
      mineralization in the vertically distracted area was seen radiographically during
      the consolidation period. In a follow up of 6-20 months after the distraction, 22
      implants were successfully osteointegrated while one implant failed due to
      improper distracted segment stability. As a result of alveolar distraction, a
      segment of mature bone was transported vertically in order to lengthen the crest
      for better implant anchorage, either for aesthetic purposes or for functional
      prosthetic requirements. The main advantages of VDO are: (1) augmentation of
      alveolar bone height with new bone formation and simultaneous expansion of the
      soft tissues; (2) no bone harvesting is necessary; (3) the technique has a lower
      morbidity rate compared with conventional techniques; (4) it makes the insertion
      of longer dental implants feasible.

PMID- 11829234
TI  - Dental extractions in patients maintained on oral anticoagulant therapy:
      comparison of INR value with occurrence of postoperative bleeding.
AB  - The purpose of this study was to evaluate the incidence of postoperative bleeding
      in patients treated with oral anticoagulant medication who underwent dental
      extractions without interruption of the treatment and to analyze the incidence of
      postoperative bleeding according to the International Normalized Ratio (INR)
      value. The 249 patients who underwent 543 dental extractions were divided into
      five groups: Group 1 with INRs of 1.5-1.99, Group 2 with INRs of 2-2.49, Group 3
      with INRs of 2.5-2.99, Group 4 with INRs of 3-3.49 and Group 5 with INRs>3.5. The
      INR was measured on the day of the procedure. Local haemostasis was carried out
      with gelatin sponge and multiple silk sutures. Of the 249 patients, 30 presented
      with postoperative bleeding (12%): Group 1, three patients presented with
      bleeding (5%), Group 2, 10 patients (12.8%), Group 3, nine patients (15.2%),
      Group 4, five patients (16.6%) and Group 5, three patients (13%). The incidence
      of postoperative bleeding was not significantly different among the five groups.
      The value of the INR at the therapeutic dose did not significantly influence the
      incidence of postoperative bleeding. Thus, dental extractions can be performed
      without modification of oral anticoagulant treatment. Local haemostasis with
      gelatin sponge and sutures appears to be sufficient to prevent postoperative
      bleeding.

PMID- 11829235
TI  - Mechanical tension in distraction osteogenesis regulates chondrocytic
      differentiation.
AB  - Differentiation of chondrocytes to cells of osteoblastic phenotype occurs during
      an interim period of bone development, fracture repair and distraction
      osteogenesis. To study the relationship between tension-stress and
      chondrogenesis, uniaxial strains (0 microstrains, 2000 microstrains, 20000
      microstrains, 200000 microstrains, 300000 microstrains) were applied in a rabbit
      model of mandibular distraction osteogenesis. The results demonstrated that cell
      differentiation, apoptosis and tissue development in the newly formed gap tissue
      showed a correlation to the applied strain magnitudes. Only strains of 20000
      microstrains resulted in a statistically significant (P<0.05) formation of
      cartilage struts with embedded chondrocyte-like cells. However, chondrocyte-like
      cells were rarely detected in samples distracted at lower or higher strain
      magnitudes. Osteoblasts appeared to replace cartilaginous matrix by mineralized
      bone matrix. The phenotypic change from chondrocytes to osteoblasts was
      accompanied by a decreased proteoglycan synthesis. a change in the expression
      from type II collagen towards type I and involved asymmetric cell divisions and
      apoptotic cell death. Therefore, we suggest that mechanical strain is an external
      stimulus responsible for phenotypic cell alterations.

PMID- 11829236
TI  - Use of cultivated osteoprogenitor cells to increase bone formation in segmental
      mandibular defects: an experimental pilot study in sheep.
AB  - The hypothesis of the present experimental pilot study was that autogeneous
      cultivated osteoprogenitor cells in porous calcium phosphate scaffolds can
      increase bone formation in segmental defects of the mandible. The autogenous
      osteoprogenitor cells of eight sheep were cultivated from bone biopsies from the
      iliac crest and seeded into cylindrical scaffolds of pyrolized bovine bone of an
      overall length of 35 mm and 13 mm in diameter. Segmental defects of 35 mm length
      were created unilaterally in the mandibles of the animals. Reconstruction was
      performed using cylinders with cultivated osteoprogenitor cells in four animals
      and empty scaffolds in the remaining four sheep, which served as controls. After
      5 months, the mandibles were retrieved and the reconstructed areas were analyzed
      by qualitative and quantitative histology in serial undecalcified thick-section
      specimens. There was significantly more bone formation in the group that had
      received scaffolds with cultivated bone cells (P=0.028). Bone formation was
      present in 34.4% of the evaluated cross-sectional units in the seeded scaffolds,
      while it was found in 10.4% in the control group. Although the spatial
      distribution of bone formation was significantly different across the scaffold in
      both groups, osteoprogenitor cells appeared to have increased bone formation,
      particularly in the centre of the defect when compared to the control group. It
      is concluded that the repair of segmental defects of the mandible can be enhanced
      by the transplantation of autogenous osteoprogenitor cells in a porous calcium
      phosphate scaffold.

PMID- 11829237
TI  - Genetic analysis of DNA microsatellite loci in salivary gland tumours: comparison
      with immunohistochemical detection of hMSH2 and p53 proteins.
AB  - To investigate genetic alterations in salivary gland tumours, microsatellite
      instability at eight representative loci and loss of heterozygosity (LOH) on
      chromosome 17 were analysed by polymerase chain reaction amplification. The
      results were compared with immunohistochemical expression of the hMSH2 and p53
      proteins. Microsatellite instability and expression loss of hMSH2 protein were
      not recognized in the salivary gland tumours, suggesting a low frequency of
      abnormalities of the mismatch repair system. LOH associated with the p53 gene was
      detected in approximately one-half of pleomorphic adenomas and salivary
      carcinomas, which often showed strong p53 immunoreactivity. These features
      suggest that the p53 gene plays an important role in malignant transformation of
      salivary gland tumours. The genetic characteristics of pleomorphic adenomas might
      reflect a low-grade potential for malignant progression.

PMID- 11829238
TI  - Rotated subcondylar process fracture in the growing animal: an experimental study
      in rats.
AB  - Unilateral, rotated subcondylar fractures were surgically induced in young rats
      under general anaesthesia. A decrease in body weight was observed in the
      fractured animals, with recovery at the end of the experimental period. A
      tendency of deviation of the mandible to the fracture side was noticed on axial
      radiographs, but without significant difference between experimental and sham
      operated animals. Histological data initially demonstrated acute inflammation
      along the articular capsule and adjacent muscle fibres. Within 2 weeks, exuberant
      callus formation occurred. Neither devitalized bone ends nor intra-articular
      granulation tissue were seen. After 1 month, the temporomandibular joint
      presented characteristics of normality, with the condylar process centralized
      into the temporal fossa, interposed by the articular disc. These results were
      preserved after 3 months. We concluded that rotational subcondylar fractures in
      young rats heal by callus formation, with simultaneous and prompt repositioning
      of the condyle.

PMID- 11829239
TI  - An evaluation of complications following dental extractions using either sterile
      or clean gloves.
AB  - This randomized prospective study aims to evaluate any differences in the
      postoperative infection rate from dental extraction using either sterile or clean
      surgical gloves and to determine any predisposing factors that may complicate
      socket healing. A total of 609 patients were randomly assigned to two groups,
      with the operators wearing either sterile or clean gloves in performing forcep
      extractions. 551 patients, who had 811 extractions performed, returned for the
      postoperative assessment visit. There was no difference in the incidence of an
      acutely inflamed socket, acutely infected socket and dry socket and also no
      significant predisposing factors found between the sterile and clean glove
      groups. The pre-operative diagnosis of caries, periodontal disease or retained
      root had a higher tendency of producing an acute-inflamed socket, whereas an
      acutely infected socket only developed in the cases of retained root. On the pain
      intensity level, an acutely inflamed socket caused mild to moderate pain, on
      acutely infected socket caused moderate to severe pain; and a dry socket caused
      severe pain in the majority of cases. The study concluded that the use of sterile
      surgical gloves does not offer an advantage over clean gloves in minimizing
      socket inflammation, infection, as well as a dry socket following dental
      extraction.

PMID- 11829240
TI  - An effective technique for open reduction of mandibular angle fractures using new
      reduction forceps: technical innovations.
AB  - We demonstrate a new technique that is useful for precompressing and holding
      mandibular angle fractures by means of new reduction forceps. The forceps were
      designed for application in the mandibular angle area via a transoral approach.

PMID- 11829241
TI  - Early clinical diagnosis of solitary plasmacytoma of the jaws: a case report with
      a six year follow-up.
AB  - The authors reported a case of a solitary mandibular plasmacytoma in a 53-year
      old male Caucasian patient. The histological examination of the specimen was
      positive for a plasmacytoma with anaplastic appearance. Since the patient refused
      a demolitive surgical treatment, he was treated with a local radiation therapy of
      4000 rads over a 20-day period and polychemotherapy with cyclophosphamide,
      prednisone and melphalan. Six years after starting radiation treatment the
      patient is free of recurrent primary disease and not affected by multiple
      localization. In conclusion, the solitary bone plasmacytoma represents an initial
      stage of the multiple myeloma rather than a distinct clinical pathology.
      Unfortunately, the diagnosis of the plasmacytoma is only rarely carried out in
      the early phases of the disease. The importance of the identification of the
      initial stage without a clear M component, as in the reported case, is self
      evident, since the prognosis is related to the mass of plasmacytoma cells that
      are present at the time of the diagnosis. The purpose of this study is to report
      an extremely rare case of solitary bone plasmacytoma with a mandibular
      localization treated with radio- and polychemotherapy.

PMID- 11829242
TI  - Paradigm for pluralism: Mikhail Bakhtin and social work practice.
AB  - This article explores the work of the literary and cultural theorist and
      philosopher Mikhail Bakhtin and acknowledges him as a new voice to social work.
      In a larger context the authors argue that his ideas can help the profession
      negotiate the tricky and unsettling transition from modernity to postmodernity.
      In particular the authors explore two of his key concepts-dialogue and carnival
      and suggest that they offer creative and innovative ways to think about three
      enduring issues in social work practice: (1) empowerment and social justice, (2)
      the creation of knowledge for practice, and (3) diversity and difference. Overall
      Bakhtin's thoughts provide the profession with a paradigm for pluralism that the
      authors believe will add new credibility and strength to the profession and its
      practitioners.

PMID- 11829243
TI  - Empowerment as a dynamically developing concept for practice: lessons learned
      from organizational ethnography.
AB  - This article describes the process of developing an empowerment approach in a
      comprehensive child development program that defined its mission as empowerment
      of families living in poverty. This description is derived from a seven-year
      organizational ethnographic research project that included data from participant
      observation, agency documents, individual interviews of staff and family
      participants, and focus group interviews with staff. Findings concerning
      empowerment are presented in two areas: (1) resolution of contrasts and
      dichotomies related to the nature of services, understanding staff roles, and
      working with the federal government; and (2) lessons learned forprogram
      effectiveness. Implications for empowerment-oriented social work practice and
      policy are offered.

PMID- 11829244
TI  - Empowering African American custodial grandparents.
AB  - The increase in grandparent-headed households is receiving much attention as the
      needs and concerns of these grandparents become more widely known. However, to
      the extent that services focus on the problems of this population, there is an
      inherent danger in overlooking their unique strengths and abilities. Empowerment
      training builds on these strengths to enable people to develop self-efficacy and
      their own problem-solving skills. In so doing, those empowered grandparents
      further empower the communities in which they live. This article describes an
      empowerment training project and its curriculum that was developed for a group of
      African American grandparents. The program resulted in strengthened parenting
      skills, and development of the participants into community peer educators.

PMID- 11829245
TI  - Client or former client? Implications of ex-client definition on social work
      practice.
AB  - The study discussed in this article investigated the effect of the variation in
      individual worker definition of "former client" in relationship to workers'
      perceptions of appropriate professional behaviors during the provision of social
      work services. A random sample of 654 social workers who possessed MSW degrees,
      provided direct services to clients, and were members of NASW were surveyed
      regarding their perceptions of appropriate behavior in seven practice domains:
      peripheral professional advice, concrete assistance, multiple or dual
      relationships, sexual and intimate relations, confidentiality and privacy, social
      relationships, and religion and prayer in practice. Variations in practice
      behavior perceptions were analyzed in relationship to the worker's definition of
      an "ex-client." The overall findings suggest that there is a definite lack of
      consensus regarding the definition of a former client, and that this may affect
      practice standards and variations in views of appropriate professional behavior.

PMID- 11829246
TI  - Sexual harassment between same-sex peers: intersection of mental health,
      homophobia, and sexual violence in schools.
AB  - This article provides a historical and legal framework for defining peer sexual
      harassment from three different perspectives: sex discrimination, mental health,
      and sexual violence. Major court decisions that define sexual harassment in both
      education and the workplace are highlighted, and arguments regarding sexual
      harassment between peers of the same sex are profiled. This research also
      identifies sexism and heterosexism as a major social violence problem in U.S.
      education and argues that peer sexual harassment is sexual violence with
      considerable mental health implications for both boys and girls. Recommendations
      for social work practice regarding peer sexual harassment in schools are
      discussed.

PMID- 11829247
TI  - Is social work's door open to people recovering from psychiatric disabilities?
AB  - Social workers are the major providers of mental health services in the United
      States, yet the profession has been reluctant to include recovering consumers in
      its ranks. This article contrasts social work's historic focus on the deficits
      believed to be inherent in colleagues' history of psychiatric disorder with an
      empowerment perspective. The article describes perceived risks and benefits to
      clients when the social worker has a history of a psychiatric disorder. It
      reviews recovering consumers' successful roles as paraprofessionals in mental
      health services delivery as a demonstration of the strengths consumers bring to
      the mental health field. Finally, it identifies barriers to social work
      employment faced by the social worker who has a history of a psychiatric
      disability.

PMID- 11829248
TI  - Knowledge diffusion in social work: a new approach to bridging the gap.
AB  - The continuing gap between research and practice has long been a problem in
      social work. A great deal of the empirical practice literature has emphasized
      practice evaluation (usually in the form of single-case methodologies) at the
      expense of research dissemination and utilization. An alternative focus for
      social work researchers can be found in the extensive theoretical and research
      literature on knowledge diffusion, technology transfer, and social marketing.
      Knowledge diffusion and social marketing theory is explored in terms of its
      relevance to social work education and practice, including a consideration of
      issues of culture and power. The authors present an integrated dissemination
      model for social work and use a case example to illustrate the practical
      application of the model. The OPTIONS (OutPatient Treatment In ONtario Services)
      project is an example of the effective dissemination of two research-based
      addiction treatment modalities to nearly 1,000 direct practice clinicians in
      Ontario, Canada.

PMID- 11829249
TI  - Embodied practice: claiming the body's experience, agency, and knowledge for
      social work.
AB  - Although social work practice typically is concerned with physical conditions and
      experiences such as poverty, addiction, and violence, relatively little attention
      has been given to the body in professional literature. Emphasizing both physical
      and sociocultural dimensions of the body, this article argues for an invigorated,
      more complex understanding of the body in social work theory, practice, and
      research. Drawing from scholarship in the humanities, social sciences, and social
      work, a framework involving three dimensions of the body is proposed for
      integration with accepted ecological practice models. The nature and implications
      of three primary dimensions of the body for multiple domains of social work
      practice are explored, citing examples from narratives of mothers living with HIV
      disease: (1) the experiencing body, focused on the physicality of daily life; (2)
      the body of power, focused on the physicality of oppression and marginality,
      typically based on race or ethnicity, socioeconomic status, gender, sexual
      orientation, age, disability, physical appearance, and illness; and (3) the
      client body, reflecting the bodily experiences of those identified as clients who
      participate in relationships with social workers.

PMID- 11829250
TI  - Harvard study finds BSE poses little threat to U.S. consumers, agriculture.

PMID- 11829251
TI  - Newer programs prove popular at AAEP convention. American Association of Equine
      Practitioners.

PMID- 11829252
TI  - Zoonoses control: hurdles, headaches, and solutions.

PMID- 11829253
TI  - Finds article on enteroplication confusing.

PMID- 11829254
TI  - More thoughts on ovarian remnant syndrome.

PMID- 11829255
TI  - More thoughts on ovarian remnant syndrome.

PMID- 11829256
TI  - What is your diagnosis? Displaced avulsion fracture of the basisphenoid
      basioccipital bone.

PMID- 11829257
TI  - Help with pricing and practice efficiency is here.

PMID- 11829259
TI  - The role of veterinary practitioners in reducing dog and cat relinquishments and
      euthanasias.

PMID- 11829258
TI  - Anesthesia case of the month. Paroxysmal supraventricular tachycardia.

PMID- 11829260
TI  - Dog parks--are they a liability risk?

PMID- 11829261
TI  - Challenges of pain assessment in domestic animals.

PMID- 11829262
TI  - Babesia gibsoni infection among dogs in the southeastern United States.
AB  - OBJECTIVE: To identify subclinical Babesia gibsoni infection in American Pit Bull
      Terriers from the southeastern United States and to determine the genetic
      sequence of parasite DNA isolated from these dogs. DESIGN: Case series. ANIMALS:
      33 American Pit Bull Terriers and 87 dogs of various other breeds. PROCEDURE:
      Blood smears were examined for microscopic evidence of the parasite, and DNA was
      extracted from blood samples and used in a polymerase chain reaction (PCR) assay
      designed to amplify the small subunit ribosomal RNA gene sequence of B. gibsoni.
      Amplification products of the expected size were sequenced, and sequences were
      compared with published sequences for B. gibsoni isolates. Hematocrit, platelet
      count, mean platelet volume, WBC count, and eosinophil count were compared
      between dogs with positive PCR assay results and dogs with negative results.
      RESULTS: Results of the PCR assay were positive for 18 of the 33 (55%) American
      Pit Bull Terriers, including all 10 dogs with microscopic evidence of
      parasitemia. Only 1 of these dogs was clinically ill at the time blood samples
      were collected. Results of microscopic evaluation of blood smears and of the PCR
      assay were negative for the 87 other dogs. Hematocrit and platelet count were
      significantly lower in dogs with positive PCR assay results than in dogs with
      negative results. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that
      American Pit Bull Terriers in the southeastern United States may be subclinically
      infected with B. gibsoni. However, subclinical infection was not identified in
      dogs of other breeds from the same geographic area.

PMID- 11829263
TI  - Efficacy of a combination febantel-praziquantel-pyrantel product, with or without
      vaccination with a commercial Giardia vaccine, for treatment of dogs with
      naturally occurring giardiasis.
AB  - OBJECTIVE: To determine efficacy of treatment with a combination febantel
      praziquantel-pyrantel product, with or without vaccination with a commercial
      Giardia vaccine, in dogs with naturally occurring giardiasis. DESIGN: Prospective
      trial. ANIMALS: 16 Beagles naturally infected with Giardia duodenalis.
      PROCEDURES: During phase 1, 6 dogs were treated with the parasiticide for 3 days
      (4 were also vaccinated). Four weeks later, all 6 dogs were treated with the
      parasiticide again for 5 days and were bathed and moved to clean cages after the
      last treatment (phase 2). Nine dogs were treated with the parasiticide for 3 (n =
      4) or 5 (5) days and bathed and moved to clean cages after the last treatment
      (phase 3). Fecal samples were collected twice weekly for 24 days after treatment
      and tested for cysts with a quantitative zinc sulfate flotation technique and for
      Giardia antigen with an immunoassay. RESULTS: Dogs in phase 1 were all shedding
      cysts again by day 24. In phase 2, only 1 dog shed cysts after treatment, and
      shedding was transient (day 17). In phase 3, neither cysts nor antigen was
      detected in fecal samples from 2 of 4 dogs treated for 3 days and 4 of 5 dogs
      treated for 5 days. In 18 of 57 (31.6%) fecal samples, cysts were seen, but
      results of the immunoassay were negative. CONCLUSIONS AND CLINICAL RELEVANCE:
      Results suggest that when a combination febantel-praziquantel-pyrantel product is
      used to treat dogs with giardiasis, bathing and changing the environment after
      treatment may be more important in preventing recurrence than duration of
      treatment.

PMID- 11829264
TI  - Evaluation of tension obtained by use of three knots for tying cerclage wires by
      surgeons of various abilities and experience.
AB  - OBJECTIVE: To compare tension of 3 cerclage wire knots tied by surgeons of
      various abilities and experience. DESIGN: Cross-sectional study. SAMPLE
      POPULATION: Participants and faculty at a postgraduate course in veterinary
      orthopedics. PROCEDURE: Subjects tied a cerclage of their choice on an
      instrumented tying stand that displayed the tension on a computer. Mean tensions
      in cerclage wires tied with twist, single loop, or double loop knots were
      compared. The relationship between level of surgeon experience and tension
      achieved was examined. RESULTS: 29 twist, 30 single loop, and 16 double loop
      wires were analyzed. Mean +/- SD tension for twist knots was significantly less
      than for single loop knots (82.3+/-46.1 vs 166.6+/-42.2 N, respectively). Double
      loop knots achieved significantly greater tension (392.0+/-116.6 N) than twist
      and single loop knots did, even though few participants had ever tied this knot
      previously. There was no correlation with experience of the participant. For
      twist knots, wiggling the wire during cutting and pushing the twist over to
      flatten it to the bone further reduced tension. CONCLUSIONS AND CLINICAL
      RELEVANCE: Cerclage applied with a twist knot does not compress fracture
      fragments as effectively as cerclage applied with single loop or double loop
      techniques. Because greater compression of fragments will improve the stability
      of a fracture, a surgeon should strive to maximize the tension in the cerclage
      that they use. Experience and abilities of the surgeon are not associated with
      ability to tie cerclage wires tightly.

PMID- 11829265
TI  - Outcome of ameroid constrictor occlusion of single congenital extrahepatic
      portosystemic shunts in cats: 12 cases (1993-2000).
AB  - OBJECTIVE: To determine postoperative (< or = 6 days), short-term (< or = 90
      days), and long-term (> or = 6 months) outcomes of cats undergoing ameroid
      constrictor occlusion of single congenital extrahepatic portosystemic shunts
      (PSS) and identify factors associated with outcome. DESIGN: Retrospective study.
      ANIMALS: 12 cats. PROCEDURE: Cats with single congenital PSS that underwent
      surgical placement of ameroid constrictors were identified. Follow-up information
      was obtained through telephone interviews and facsimile correspondence with
      referring veterinarians and owners. Results-All cats survived the surgery and
      were discharged from the hospital. One cat had seizures during the postoperative
      period. Five cats were clinically normal during follow-up evaluations within 90
      days after the surgery. Long-term follow-up information was available for 9 cats.
      Three were clinically normal, 4 had been euthanatized because of progressive
      neurologic disease, and 2 had neurologic abnormalities that could not be
      controlled with medication. Four of 7 cats with continued or recurrent neurologic
      abnormalities 1 or more months after surgery had normal scintigraphic or hepatic
      function test results 2 to 6 months after surgery. CONCLUSIONS AND CLINICAL
      RELEVANCE: Results suggest that the long-term outcome of ameroid constrictor
      occlusion of PSS in cats is poor. Owners of older cats and cats with preexisting
      neurologic signs should be made aware of the potential for a poor outcome when
      considering surgical correction of this disease.

PMID- 11829266
TI  - Population-based study of fecal shedding of Clostridium perfringens in broodmares
      and foals.
AB  - OBJECTIVE: To determine the percentage of broodmares and foals that shed
      Clostridium perfringens in their feces and classify the genotypes of those
      isolates. DESIGN: Prospective cross-sectional study. ANIMALS: 128 broodmares and
      their foals on 6 equine premises. PROCEDURES: Anaerobic and aerobic bacteriologic
      cultures were performed on feces collected 3 times from broodmares and foals. All
      isolates of C. perfringens were genotyped. RESULTS: Clostridium perfringens was
      isolated from the feces of 90% of 3-day-old foals and 64% of foals at 8 to 12
      hours of age. A lower percentage of broodmares and 1- to 2-month-old foals shed
      C. perfringens in their feces, compared with neonatal foals. Among samples with
      positive results, C. perfringens type A was the most common genotype identified
      (85%); C. perfringens type A with the beta2 toxin gene was identified in 12% of
      samples, C. perfringens type A with the enterotoxin gene was identified in 2.1%
      of samples, and C. perfringens type C was identified in < 1% of samples.
      CONCLUSIONS AND CLINICAL RELEVANCE: Clostridium perfringens was identified from
      the feces of all but 6 foals by 3 days of age and is likely part of the normal
      microflora of neonatal foals. Most isolates from broodmares and foals are C.
      perfringens type A; thus, the clinical relevance of culture results alone is
      questionable. Clostridium perfringens type C, which has been associated with
      neonatal enterocolitis, is rarely found in the feces of horses.

PMID- 11829267
TI  - Clinical signs and treatment of chronic uterine torsion in two mares.
AB  - Two mares were evaluated because of chronic uterine torsions of 2 and 4 weeks'
      duration; both were pyrectic, anemic, tachycardic, and anorectic, had signs of
      depression, and had an abnormal uterus and contents on transrectal examination.
      Both mares underwent cesarean section for lysis of adhesions from the uterus to
      the peritoneum, correction of the torsion, and ovariohysterectomy Both mares
      recovered with only minor complications and returned to be used as riding horses.
      Chronic uterine torsion should be considered in mares in late stages of gestation
      that have vague clinical signs and transrectal palpation findings that are unlike
      those described in typical cases of uterine torsion. Prognosis for life can be
      good after treatment by ventral midline celiotomy, cesarean section, correction
      of the torsion, and ovariohysterectomy.

PMID- 11829268
TI  - Surgical management of a ureteral defect with ureterorrhaphy and of ureteritis
      with ureteroneocystostomy in a foal.
AB  - A 2-day-old male foal developed uroperitoneum. Initial exploration of the abdomen
      via ventral midline celiotomy failed to localize the source of uroperitoneum.
      Bilateral nephropyelocentesis and antegrade urography were performed, and a
      defect in the right ureter and stenosis of the left ureter were identified. With
      the foal in dorsal recumbency in the Trendelenburg position, ureterorrhaphy was
      performed on the right ureter. After ureterorrhaphy, a ureteral catheter was
      maintained as a stent. The stenotic left ureter was transected, and
      ureteroneocystostomy was performed using a drop-in mucosal apposition technique.
      The ureteral catheter was removed 26 days after surgery. Histopathologic findings
      suggested that ureteritis of unknown origin was a possible initiating factor for
      stenosis of the left ureter. The drop-in technique for ureteroneocystostomy may
      be used successfully for ureteral transposition in horses. Ureterorrhaphy
      combined with the use of a ureteral stent may be used to repair ureteral defects
      in foals.

PMID- 11829269
TI  - Prevalence of Salmonella spp in selected birds captured on California dairies.
AB  - OBJECTIVE: To determine the prevalence of Salmonella spp in wild birds commonly
      found on California dairies. DESIGN: Prospective study. ANIMALS: 7 selected
      species of birds were captured on 9 dairies in Kings and Tulare counties,
      California. PROCEDURE: Birds were captured (using traps and nets) and
      euthanatized, and the entire gastrointestinal tract was removed. Contents of the
      gastrointestinal tract were subjected to culture for Salmonella spp. RESULTS: 892
      birds were captured, and Salmonella spp were isolated from 22 birds. The
      prevalence by dairy ranged from 0.7 to 16.7%, whereas the prevalence by bird
      species ranged from 1.2 to 3.2%. Cowbirds and English sparrows had the highest
      prevalence of Salmonella organisms. Five serotypes of Salmonella organisms were
      isolated, including Meleagridis, Montevideo, Muenster, Typhimurium, and an
      untyped serotype. CONCLUSIONS AND CLINICAL RELEVANCE: On the basis of our
      findings, birds that commonly inhabit California dairies harbor Salmonella
      organisms. However, because of the low prevalence of Salmonella organisms in
      birds and the Salmonella serotypes isolated, birds are not important reservoirs
      of Salmonella organisms on California dairies.

PMID- 11829270
TI  - Heinz-body hemolytic anemia associated with ingestion of methylene blue in a
      river otter.
AB  - Heinz-body hemolytic anemia and nephrosis associated with hemoglobinuria were
      diagnosed in a North American river otter. Fluids were administered, and the
      signs of renal failure improved immediately. Severe anemia developed, and the
      otter received a semisynthetic hemoglobin product to maintain the oxygen-carrying
      capacity of the blood until a blood transfusion could be given. Immediate
      clinical improvement was observed following hemoglobin administration, and
      adverse effects were not seen. Six days after admission, the otter began to
      produce its own RBC and recovered without complications. The Heinz-body anemia
      was determined to be caused by methylene blue that was in the water of minnows
      consumed by the otter the night before it became ill. Methylene blue is a common
      ingredient in products used to extend the life of bait fish. Bait fish kept in
      water treated with methylene blue should not be used as food for fish-eating
      animals.

PMID- 11829271
TI  - Building a research program focused on vulnerable people.
AB  - The center is playing an important role in facilitating research by providing
      resources and an interchange of ideas to help researchers target the
      methodological and conceptual issues with which they are currently faced in
      working with elder, young, poor, rural, and minority participants. Through
      activities and collaborations, the center can advance the science beyond what
      individual studies can provide and continue to build our knowledge of the
      prevention and management of chronic illness in vulnerable people. The center is
      ideally positioned to explore interventions that draw on nursing's historic role
      in the care of the chronically ill while also addressing the health needs of the
      most vulnerable people in the state and in the Southeast.

PMID- 11829272
TI  - Emotional well-being in a person with dementia.
AB  - Self-reported mood and observations of affect are often used as indicators of
      emotional well-being. The purpose of this case study was to (a) describe the self
      reported mood and affective pattern of an older man with severe cognitive
      impairments, (b) assess consistency in his responses to mood state, (c) compare
      mood pattern to premorbid personality, and (d) determine the concordance between
      self-reported mood and observed affect. Observations of mood and affect were
      taken three times per day for 35 days. There was concordance between self
      reported mood and observed affect. The participant was consistent in his
      responses to mood 75% of the time. The pattern of self-reported mood reflected
      the participant's long-standing personality traits of extraversion and
      neuroticism. Results, although not generalizable, demonstrate the need to
      consider the perspective of the person with dementia when addressing quality-of
      life issues in research and practice.

PMID- 11829273
TI  - Differential predictors of emotional distress in HIV-infected men and women.
AB  - Changes in the AIDS epidemic in many areas of the United States require
      information about the experience of the growing segment of women afflicted. This
      study compared patterns of emotional distress between men and women with
      symptomatic HIV and examined potential predictors of different levels of
      vulnerability. A sample of 126 low socioeconomic men and women seeking care from
      HIV treatment centers was surveyed using measures of physical and psychological
      well-being. Women had more HIV symptoms, poorer functioning, and greater
      disruptions in physical and psychosocial well-being. Physical health status and
      optimism were primary predictors of emotional distress in both men and women.
      More than 50% of men and women had scores indicative of clinical anxiety.
      Approximately 1 out of 10 had clinically relevant scores for depression. Gender
      differences may provide potentially useful information for tailoring assessment
      interventions for emotional distress in people infected with HIV.

PMID- 11829274
TI  - Eat healthy--eat sugar.

PMID- 11829275
TI  - Focused life stories of women with cardiac pacemakers.
AB  - Biotechnical devices such as cardiac pacemakers are implanted into people to
      manage a range of disorders, yet comparatively little is known about the
      emotional impact of this experience. Women may have a unique response to
      implanted devices due to cultural messages about the masculinity of technology.
      In this qualitative study using Hall's focused life stories design, 11 women from
      teenagers to elders with permanent cardiac pacemakers were asked to describe
      their experiences using semistructured interviews. The themes that emerged are
      relinquishing care, owning the device, experiencing fears and/or resistance,
      imaging the body, normalizing, positioning as caretaker, finding resilience, and
      sensing omnipotence. Understanding what it means for women to live with an
      implanted biotechnical device may facilitate planning interventions to support
      their psychological and physiological health. Effective pacemaker function may
      depend, in part, on recipients' successful emotional attachment to the device.

PMID- 11829276
TI  - Health-promoting self-care in family caregivers.
AB  - Caregiving for family members with cognitive impairment is stressful and time
      consuming. Because of the attention needed to manage the memory and behavior
      problems of the care receiver, family caregivers have little time to attend to
      their own health needs. Most research related to the health of family caregivers
      has been conducted within a stress-illness framework. Fewer researchers have
      studied caregiver health from a health-promotion paradigm. The purpose of this
      study was to compare health-promoting self-care behavior infamily caregivers with
      demographically matched noncaregivers and to investigate the mediational effect
      of health-promoting self-care behavior on the relationship between stress and
      well-being. Findings revealed that family caregivers scored significantly lower
      on all measures of health promotion, with the exception of Nutrition and Number
      of Medications, and significantly higher on Barriers to Health-Promoting Actions.
      Health-promoting self-care behavior acted as a mediator to reduce the effect of
      caregiver stress on general well-being.

PMID- 11829277
TI  - Critical elements of documentation for data-based research.
AB  - Scientific integrity and progress are enhanced by precise documentation of the
      conceptual development and information management aspects of research. Careful
      and complete documentation of the research process supports accurate reporting.
      The exercise of documenting data management activities provides an opportunity
      for nurse researchers to reflect on a study to guide current work and inform and
      enhance future research. The literature includes many references to the need for
      data management but contains little advice regarding the nuts and bolts of
      documenting data management activities. This article describes specific steps for
      documenting data-based research beginning with the study design and ending with
      data analysis. The documentation framework and examples presented are sufficient
      to guide the comprehensive record keeping required for complex studies and can be
      modified to meet the simpler needs of smaller research projects.

PMID- 11829278
TI  - Immune dysfunction in cancer patients.
AB  - Immune deficiency in cancer patients is well documented, and tumor cells have
      developed a variety of cellular and molecular mechanisms to avoid antitumor
      immune responses. These mechanisms include defective presentation of tumor
      antigens on the cell surface and/or an inability of the host to effectively
      recognize these cells and target them for destruction. Tumor-induced defects are
      known to occur in all major branches of the immune system. The continuous
      administration of vascular endothelial growth factor (VEGF), a factor produced by
      most solid tumors, inhibits the functional maturation of dendritic cells,
      significantly decreases T-cell to B-cell ratios in the peripheral lymphoid
      organs, and induces rapid and dramatic thymic atrophy in tumor-bearing animals.
      VEGF is abundantly expressed by a large percentage of solid tumors, and defective
      antigen presentation, T-cell defects, and premature thymic atrophy are known to
      occur in cancer patients and tumor-bearing animals. This review will encompass
      the major mechanisms responsible for tumor evasion of immune surveillance and
      highlight a role for VEGF as a principal contributor to tumor-associated immune
      deficiencies.

PMID- 11829279
TI  - DC2 effect on survival following allogeneic bone marrow transplantation.
AB  - The graft-vs-tumor effect is an important part of the curative potential of
      allogeneic transplantation. We characterized the effect of transplanted donor
      mononuclear cells on relapse- and event-free survival after allogeneic bone
      marrow transplantation (BMT). We studied 113 consecutive patients with
      hematologic malignancies who received non-T-cell-depleted BMT from human
      leukocyte antigen (HLA)-matched siblings. Most patients (n = 103) received
      busulfan (Myleran)-based conditioning, and all patients received standard short
      course methotrexate and tacrolimus (Prograf) as graft-vs-host disease
      prophylaxis. Sixty-four patients had low-risk diagnoses (acute lymphoblastic
      leukemia/acute myeloid leukemia [first complete remission], myelodysplastic
      syndrome [refractory anemia/refractory anemia with ring sideroblasts], and
      chronic myeloid leukemia [first chronic phase]); 49 patients had high-risk
      diagnoses (all others). Cox regression analyses evaluated risk strata, age,
      gender, and the numbers of nucleated cells, CD3-positive T cells, CD34-positive
      hematopoietic cells, and type 2 dendritic cells (DC2) as covariates for event
      free survival, relapse, and nonrelapse mortality. Recipients of larger numbers of
      DC2 cells had significantly lower event-free survival, a lower incidence of
      chronic graft-vs-host disease, and an increased incidence of relapse. Recipients
      of larger numbers of CD34-positive cells had improved event-free survival;
      recipients of fewer CD34-positive cells had delayed hematopoietic engraftment and
      increased death from infections. In conclusion, content of donor DC2 cells was
      associated with decreased chronic graft-vs-host disease and graft-vs-leukemia
      effects consistent with Th2/Tc2 polarization of donor Tcells following allogeneic
      bone marrow transplantation.

PMID- 11829280
TI  - Dendritic cell function in sentinel nodes.
AB  - Intraoperative lymphatic mapping and sentinel lymphadenectomy has become an
      increasingly popular technique for staging the regional lymph nodes in early
      stage melanoma. This operative technique allows for detailed pathologic analysis
      of the first (or sentinel) lymph node in direct connection with the primary
      tumor, and provides a unique opportunity for assessing potential immunologic
      interactions between the primary tumor and regional lymph node basin. We
      performed lymphatic mapping and sentinel lymphadenectomy on 25 patients with
      early-stage melanoma and resected an additional nonsentinel node in each case.
      Sentinel and nonsentinel nodes were evaluated by routine pathologic analysis. A
      portion of each node was processed for expression of the dendritic markers of
      activation CD80, CD86, and CD40, and their corresponding T-cell receptors CTLA-4
      and CD28. Of 25 patients undergoing lymphatic mapping and sentinel
      lymphadenectomy, 20 (80%) had matched sentinel and nonsentinel nodes. A total of
      26 matched lymph node sets were obtained: three pairs from one patient and two
      from an additional two patients. Reverse transcription polymerase chain reaction
      analyses of corresponding sections of the sentinel and nonsentinel nodes
      demonstrated a marked reduction in semiquantitative expression of CD80 (77%),
      CD86 (77%), and CD40 (85%), as well as CTLA-4 (88%) and CD28 (85%) in sentinel as
      compared to nonsentinel nodes. The diminished expression of the dendritic cell
      markers appeared to be unrelated to the B-cell (CD20) and T-cell (CD2)
      expression. Lymphatic mapping and sentinel lymphadenectomy allows for detailed
      pathologic and molecular characterization of sentinel nodes. Our results suggest
      a quantitative reduction in dendritic cell markers in sentinel as compared to
      nonsentinel nodes, which may be important in the immunologic interaction between
      the primary site and regional lymph node basin and may also serve as useful
      criteria for identifying sentinel nodes.

PMID- 11829281
TI  - Adjuvant therapy of melanoma.
AB  - In 2001, the American Joint Committee on Cancer Melanoma Staging Committee
      proposed and created a new staging system for melanoma. This new system will
      become official in 2002, with the publication of the sixth edition of the AJCC
      Cancer Staging Manual. The new system identifies significant prognostic variables
      in patients with melanoma and validates them in an analysis of 17,600 patients,
      making it possible to precisely determine the patient's chance for survival In
      light of physicians' ability to determine with more precision which patients are
      at high risk for melanoma recurrence, they face the dilemma of which, if any,
      surgical adjuvant therapy to choose. Alpha-interferon is the only agent approved
      for adjuvant therapy of melanoma in the United States, but its questionable
      benefits and substantial side effects make it hard to justify recommending it to
      patients. Discussion of trials of high- and low-dose interferon is presented
      here. The author's group has conducted trials of granulocyte-macrophage colony
      stimulating factor (GM-CSF [Leukine]) as surgical adjuvant treatment of patients
      at high-risk for melanoma recurrence. One of the most important activities of GM
      CSF is its ability to activate macrophages and cause them to become cytotoxic for
      human melanoma cells, at doses low enough to avoid the toxicity associated with
      other cytokines. The author presents promising trial results, discusses GM-CSF in
      other malignancies, and includes discussion of tumor vaccines, biochemotherapy,
      and other agents being studied as adjuvant therapy of melanoma. It is hoped that
      these newer approaches will result in therapies that are more effective and less
      toxic than interferon.

PMID- 11829282
TI  - Beyond neutrophil recovery: manipulation of the tumor microenvironment by GM-CSF
      to control cancer.

PMID- 11829283
TI  - Speed and safety effect of photo radar enforcement on a highway corridor in
      British Columbia.
AB  - This study evaluates the effect of the photo radar program on traffic speed and
      collisions at photo radar (PRP) influence locations (PRP location) and
      interleaving non-PRP locations on the Vancouver Island portion of Highway 17 (Pat
      Bay Highway) in British Columbia (BC). Simple before-after comparison was used to
      summarize the speed effect while observational before- after method was employed
      to estimate the safety effect. To control for regression to the mean and time
      effect, Empirical Bayes (EB) method with comparison groups was employed in
      collision analysis. The study found a 2.8-km/h reduction in mean speed and a 0.5
      km/h reduction in speed standard deviation at a monitoring site 2 km south of the
      treatment area. Corresponding to speed reduction. the study revealed a 14%+/-11%
      reduction in expected collisions at the PRP locations, a 19%+/-10% reduction at
      the non-PRP locations, and a 16%+/-7% reduction along the study corridor as a
      whole. No evidence was found for a localized effect in a 2-km range of the photo
      radar direct influence area, over and above those at the interleaving non-PRP
      locations. The results support the hypothesis of a distance spillover effect-
      that the program not only improved safety at the PRP locations, but along the
      entire enforcement corridor as well. It suggests that the unpredictable nature of
      the deployments lead drivers to modify their behavior along the length of the
      corridor because they could not discern 'safe' from 'unsafe' segments.

PMID- 11829284
TI  - Predicting seat belt use in fatal motor vehicle crashes from observation surveys
      of belt use.
AB  - There is a large difference between the rates of observed seat belt use by the
      general public and belt use by motor vehicle occupants who are fatally injured in
      crashes. Seat belt use rates of fatally injured occupants, as reported in the
      Fatality Analysis Reporting System (FARS), are much lower than the use rates
      found in observation surveys conducted by the states. A series of mathematical
      models describing the empirical relationship between FARS and observed rates were
      explored. The initial model was a 'straw man' and used two simplifying
      assumptions: (a) belt users and nonusers are equally likely to be involved in
      'potentially fatal collisions', and (b) belts are 45% effective in preventing
      deaths. The model was examined by comparing each state's FARS use rate with the
      predicted rate. The model did not fit the state data points even when possible
      biases in the data were controlled. We next examined the assumptions in the
      model. Changing the seat belt effectiveness parameter provided a reasonable fit,
      but required an assumption that seat belts are 67% effective in preventing
      fatalities. The inclusion of a risk coefficient for non-belted occupants also
      provided a reasonable fit between the model and data. A variable risk model
      produced the best fit with the data. The major finding was that a model
      consistent with the data can be obtained by incorporating the assumption that
      nonusers of seat belts have a higher risk of involvement in potentially fatal
      collisions than do seat belt users. It was concluded that unbelted occupants are
      over-represented in fatal collisions for two reasons: (a) because of a greater
      chance of involvement in potentially fatal collisions in the first place, and (b)
      because they are not afforded the protection of seat belts when a collision does
      occur.

PMID- 11829285
TI  - Impact of roadside features on the frequency and severity of run-off-roadway
      accidents: an empirical analysis.
AB  - In the US, single-vehicle run-off-roadway accidents result in a million highway
      crashes with roadside features every year and account for approximately one third
      of all highway fatalities. Despite the number and severity of run-off-roadway
      accidents, quantification of the effect of possible countermeasures has been
      surprisingly limited due to the absence of data (particularly data on roadside
      features) needed to rigorously analyze factors affecting the frequency and
      severity of run-off-roadway accidents. This study provides some initial insight
      into this important problem by combining a number of databases, including a
      detailed database on roadside features, to analyze run-off-roadway accidents on a
      96.6-km section of highway in Washington State. Using zero-inflated count models
      and nested logit models, statistical models of accident frequency and severity
      are estimated and the findings isolate a wide range of factors that significantly
      influence the frequency and severity of run-off-roadway accidents. The marginal
      effects of these factors are computed to provide an indication on the
      effectiveness of potential countermeasures. The findings show significant promise
      in applying new methodological approaches to run-off-roadway accident analysis.

PMID- 11829286
TI  - Rollover risk of cars and light trucks after accounting for driver and
      environmental factors.
AB  - Characteristics of the driver, roadway environment, and vehicle were associated
      with the likelihood of rollover occurrence in more than 14000 single-vehicle
      fatal and 78000 single-vehicle injury crashes during 1995-98. Rollovers were more
      likely in crashes involving young drivers or occurring on rural curves. After
      accounting for the effects of driver age and gender, roadway alignment and
      surface condition, and whether or not the crash occurred in a rural area, light
      trucks were still twice as likely as cars to experience rollovers. Some light
      truck models were much more likely than others to experience rollovers. However,
      while physical differences (e.g. center of gravity height) could explain some of
      this variability, other factors affecting vehicle stability may be evident only
      after dynamic testing.

PMID- 11829287
TI  - Evaluation of a combined brake-accelerator pedal.
AB  - Over the years, designers have developed various combined brake-accelerator
      pedals in an effort to eliminate the operator's risk of pressing the wrong pedal
      as well as to reduce his or her reaction time in braking. The goal of this study
      is to highlight problems that drivers may face when they switch between pedal
      systems. Eighteen male and female drivers varying in age participated in the
      study. The evaluation was carried out during special driving maneuvers and in
      normal traffic in which all drivers used the same test vehicle. The results
      indicate that drivers were able to learn the new combined pedal mechanism quickly
      and effortlessly and that the number of mistakes was extremely low during the
      acquisition phase in learning the new system. The drivers reported that they
      preferred the combined brake-accelerator pedal to the conventional pedals, noting
      that the combined pedal offered greater physical comfort and was considerably
      more natural to operate. Because of the risk of compensation, whereby increased
      safety is forfeited as a result of reduced safety margins, future experiments of
      the new combined pedal are desirable.

PMID- 11829288
TI  - Role of drivers' personal characteristics in understanding traffic sign symbols.
AB  - This study investigated the role of age, marital status, gender, nationality,
      educational background and monthly income in drivers' comprehension of traffic
      signs. The populations sampled here were from five Arabian Gulf Countries. A
      total of 28 symbolic warning and regulatory signs were investigated. A
      questionnaire specially prepared to collect the necessary data was distributed to
      over 9000 drivers in the five countries; 4774 responded (53%). The results
      indicated substantial problems with the level of comprehension among the drivers
      about the traffic signs. The percentages of drivers who correctly identified the
      regulatory signs and warning signs were around 55 and 56%, respectively. Age,
      gender, education and income played major roles in determining drivers'
      comprehension of signs, whereas marital status showed no significant effect.
      Drivers who are young, female, those with lower levels of education or lower
      incomes understand the signs significantly worse than drivers who are older,
      male, with higher levels of education or higher incomes. Drivers from Europe and
      USA are significantly better than Asian and Arab drivers. These findings are
      believed to be important for the designers of road signs for international
      applications.

PMID- 11829289
TI  - Effects of daytime running lights on multiple-vehicle daylight crashes in the
      United States.
AB  - Involvements in multiple-vehicle daylight crashes in nine states over 4 years
      were analyzed for a group of passenger cars and light trucks equipped with
      automatic daytime running lights. On average, these vehicles were involved in
      3.2% fewer multiple-vehicle crashes than vehicles without daytime running lights
      (P = 0.0074).

PMID- 11829290
TI  - Pedestrian-vehicle crashes and analytical techniques for stratified contingency
      tables.
AB  - In 1999 there were 450 fatalities due to road crashes in Riyadh, the capital of
      Saudi Arabia, of which 130 were pedestrians. Hence, every fourth person killed on
      the roads is a pedestrian. The aim of this study is to investigate pedestrian
      vehicle crashes in this fast-growing city with two objectives in mind: to analyze
      pedestrian collisions with regard to their causes, characteristics, location of
      injury on the victim's body, and most common patterns and to determine the
      potential for use of the odds ratio technique in the analysis of stratified
      contingency tables. Data from 638 pedestrian-vehicle crashes reported by police,
      during the period 1997-1999, were used. A systematic sampling technique was
      followed in which every third record was used. The analysis showed that the
      pedestrian fatality rate per 10(5) population is 2.8. The rates were relatively
      high within the childhood (1-9 years) and young adult (10-19 years) groups, and
      the old-age groups (60 - > 80 years), which indicate that young as well as the
      elderly people in this city are more likely to be involved in fatal accidents of
      this type than are those in other age groups. The analysis revealed that 77.1% of
      pedestrians were probably struck while crossing a roadway either not in a
      crosswalk or where no crosswalk existed. In addition, the distribution of
      injuries on the victims' bodies was determined from hospital records. More than
      one-third of the fatal injuries were located on the head and chest. An attempt
      was made to conduct an association analysis between crash severity (i.e. injury
      or fatal) and some of the study variables using chi-square and odds ratio
      techniques. The categorical nature of the data helped in using these analytical
      techniques.

PMID- 11829291
TI  - Changes in crash risk following re-timing of traffic signal change intervals.
AB  - More than I million motor vehicle crashes occur annually at signalized
      intersections in the USA. The principal method used to prevent crashes associated
      with routine changes in signal indications is employment of a traffic signal
      change interval--a brief yellow and all-red period that follows the green
      indication. No universal practice exists for selecting the duration of change
      intervals, and little is known about the influence of the duration of the change
      interval on crash risk. The purpose of this study was to estimate potential crash
      effects of modifying the duration of traffic signal change intervals to conform
      with values associated with a proposed recommended practice published by the
      Institute of Transportation Engineers. A sample of 122 intersections was
      identified and randomly assigned to experimental and control groups. Of 51
      eligible experimental sites, 40 (78%) needed signal timing changes. For the 3
      year period following implementation of signal timing changes, there was an 8%
      reduction in reportable crashes at experimental sites relative to those occurring
      at control sites (P = 0.08). For injury crashes, a 12% reduction at experimental
      sites relative to those occurring at control sites was found (P = 0.03).
      Pedestrian and bicycle crashes at experimental sites decreased 37% (P = 0.03)
      relative to controls. Given these results and the relatively low cost of re
      timing traffic signals, modifying the duration of traffic signal change intervals
      to conform with values associated with the Institute of Transportation Engineers'
      proposed recommended practice should be strongly considered by transportation
      agencies to reduce the frequency of urban motor vehicle crashes.

PMID- 11829292
TI  - The relationship between body weight and risk of death and serious injury in
      motor vehicle crashes.
AB  - We sought to investigate the effect of increased body weight on the risk of death
      and serious injury to occupants in motor vehicle crashes. We employed a
      retrospective cohort study design utilizing data from the National Automotive
      Sampling System, Crashworthiness Data System (CDS), 1993-1996. Subjects in the
      study included occupants involved in tow-away crashes of passenger cars, light
      trucks, vans and sport utility vehicles. Two outcomes were analyzed: death within
      30 days of the crash and injury severity score (ISS). Two exposures were
      considered: occupant body weight and body mass index (BMI; kg/m2). Occupant
      weight was available on 27263 subjects (76%) in the CDS database. Mortality was
      0.67%. Increased body weight was associated with increased risk of mortality and
      increased risk of severe injury. The odds ratio for death was 1.013 (95% CI:
      1.007, 1.018) for each kilogram increase in body weight. The odds ratio for
      sustaining an injury with ISS > or = 9 was 1.008 (95% CI: 1.004, 1.011) for each
      kilogram increase in body weight. After adjustment for potentially confounding
      variables (age, gender, seatbelt use, seat position and vehicle curbweight), the
      significant relationship between occupant weight and mortality persisted. After
      adjustment, the relationship between occupant weight and ISS was present,
      although less marked. Similar trends were found when BMI was analyzed as the
      exposure. In conclusion, increased occupant body weight is associated with
      increased mortality in automobile crashes. This is probably due in part to
      increased co-morbid factors in the more overweight occupants. However, it is
      possibly also due to an increased severity of injury in these occupants. These
      findings may have implications for vehicle safety design, as well as for
      transport safety policy.

PMID- 11829293
TI  - Anger and aggression among drivers in three European countries.
AB  - Recent reports of 'road rage' in the British media give the impression that
      driver aggression is escalating. In order to understand this phenomenon we need
      to know what it is about driving that provokes motorists to feel anger and then
      to go on to express that anger in the form of aggression. A postal questionnaire
      survey of more than 2500 drivers was carried out in three European countries:
      Britain, Finland and the Netherlands. The study had three main aims: (a) to
      discover how angry, if at all, a range of situations on the road make drivers,
      (b) to find out how many drivers are likely to react aggressively to those
      situations, and (c) to investigate individual and/or cultural differences in
      terms of anger and/or aggressive responses among motorists. Results indicate that
      the same types of behaviour provoke anger and aggression in all three countries,
      and that traffic density may play a role.

PMID- 11829294
TI  - Evaluating the crash and citation rates of Utah drivers licensed with medical
      conditions, 1992-1996.
AB  - BACKGROUND: Medical problems may affect the ability to drive motor vehicles, and
      programs that control the issuing of driver licenses to individuals with medical
      conditions exist in most states. The main activity of these programs is the
      imposition of restrictions upon the driving privileges of individuals with
      medical conditions that are deemed to pose some risk to public safety. However,
      little is known about the effectiveness of these licensing programs. OBJECTIVE:
      The objective of this study was to compare the rates of adverse driving events
      (crash, at-fault crash and citations) experienced by drivers licensed with
      medical conditions to those of age-, sex- and location-matched controls. Separate
      comparisons were made for drivers reporting medical conditions licensed with full
      driving privileges, and those with restricted driving privileges (e.g. speed,
      area and time of day). DESIGN: Retrospective case-control. METHODS: The study
      population was all drivers licensed in the state of Utah who reported a medical
      condition on their driver license application, over the 5-year period 1992-1996.
      Drivers enter the program by self-reporting their medical problems. Control
      drivers were chosen from the entire population of drivers licensed in Utah for
      the same period. Information on driver license status, participation in the
      medical conditions program, citations, involvement in crashes, and death
      certificate data was obtained from the relevant state agencies. Probabilistic
      linkage methodology was used to link the records in these disparate databases for
      eventual analysis. Rates of citation, crashes and at-fault crashes, expressed as
      events per 10000 license days, were calculated separately for program drivers and
      their corresponding control groups for each medical condition category and
      restriction status. These data were used to determine an estimate of relative
      risk (RR) and 95% confidence intervals. RESULTS: As a group, medical conditions
      drivers had modestly elevated rates of adverse driving events compared with
      control drivers (RR 1.09-1.74). Rates in the largest medical category,
      'cardiovascular conditions', were not higher than controls. Rates were higher
      than control for some conditions, such as 'alcohol' and 'learning and memory',
      for some adverse events (RR 2.2 -5.75). Drivers with more than one medical
      condition appeared comparable to the general group of medical conditions program
      drivers. CONCLUSIONS: Drivers in Utah medical conditions program had modestly
      elevated rates of adverse driving events compared to matched controls. Possible
      underreporting of medical conditions and accurate assessment of exposure rates
      are potential weaknesses in the program.

PMID- 11829295
TI  - The neck injury criterion: future considerations.
AB  - The cost of whiplash injuries--both in dollars spent for medical care and
      disability, and in terms of human suffering--are quite high in westernized
      nations. This is of particular interest both from a public health perspective and
      a general societal one because the disorder is theoretically preventable: in the
      very least it can be minimized. This can be achieved with crash prevention
      strategies and improvements in vehicle safety design--especially with more
      effective seat back and head restraint systems. Toward the goal of developing a
      gold standard for safety research in this area, a neck injury criterion (NIC) was
      proposed by Bostrom et al. in 1996 (Bostrom O., Svennson, M.Y., Aldman, B. et
      al., 1996. In: Proceedings of the International Conference on the Biomechanics of
      Impact, Dublin, Ireland). This criterion considers the relative horizontal
      acceleration and velocity between the bottom (T1) and top (C1) of the cervical
      spine and has face validity based on current literature. However, the NIC has
      still not been subjected to rigorous scientific investigation or validation in
      terms of its representativeness of human occupant injury. Such investigation
      should specifically consider, first, whether the NIC provides an adequate proxy
      for all potential neck injuries due to whiplash and, secondly, whether the
      proposed threshold value of 15 m2/s2 is an appropriate level for the stated goal.
      Based on a review of recent literature, recent human volunteer crash tests by
      Wheeler et al. and the those of the Spine Research Institute of San Diego, and
      based on mathematical MADYMO analysis of the first real world crash pulse data,
      it appears that the threshold for acute injury in the general population is
      likely to require a lowering of the originally proposed NIC value, and additional
      parameters, such as considering a forward rebound phase or neck extension
      criteria may be necessary. The conclusions of this paper should be considered
      preliminary because the numbers of crash test subjects and real world injury
      victims does not allow for rigorous statistical analysis. Certainly, ongoing work
      will be necessary to investigate this further and larger scale analysis of more
      onboard crash data will prove invaluable.

PMID- 11829296
TI  - Previous convictions or accidents and the risk of subsequent accidents of older
      drivers.
AB  - The over-involvement of elderly drivers in collisions has a potentially adverse
      effect on highway safety. The question for most experts in traffic research is
      whether we can predict the individual risk of accidents and which variables are
      the best predictors, especially for this population. For a better understanding
      of the elderly drivers' problems, this study aimed to describe the most common
      types of accidents in the elderly population of drivers living in Quebec (> or =
      65 years of age). The second objective of the study was to analyse the
      relationship between previous accidents or convictions and the risk of subsequent
      accidents. The results show that: (1) elderly drivers are characterised by error
      accidents involving more than one car, especially at intersections, (2) prior
      accidents are a better predictor for accident risk than prior convictions and (3)
      these trends steadily increase with each age group (drivers 65 years old to 80
      years or more). The results are discussed in relation to the literature on risk
      behaviour of the elderly drivers.

PMID- 11829297
TI  - Motion direction signals in the primary visual cortex of cat and monkey.
AB  - When an image feature moves with sufficient speed it should become smeared across
      space, due to temporal integration in the visual system, effectively creating a
      spatial motion pattern that is oriented in the direction of the motion. Recent
      psychophysical evidence shows that such "motion streak signals" exist in the
      human visual system. In this study, we report neurophysiological evidence that
      these motion streak signals also exist in the primary visual cortex of cat and
      monkey. Single neuron responses were recorded for two kinds of moving stimuli:
      single spots presented at different velocities and drifting plaid patterns
      presented at different spatial and temporal frequencies. Measurements were made
      for motion perpendicular to the spatial orientation of the receptive field
      ("perpendicular motion") and for motion parallel to the spatial orientation of
      the receptive field ("parallel motion"). For moving spot stimuli, as the speed
      increases, the ratio of the responses to parallel versus perpendicular motion
      increases, and above some critical speed, the response to parallel motion exceeds
      the response to perpendicular motion. For moving plaid patterns, the average
      temporal tuning function is approximately the same for both parallel motion and
      perpendicular motion; in contrast, the spatial tuning function is quite different
      for parallel motion and perpendicular motion (band pass for the former and low
      pass for the latter). In general, the responses to spots and plaids are
      consistent with the conventional model of cortical neurons with one rather
      surprising exception: Many cortical neurons appear to be direction selective for
      parallel motion. We propose a simple explanation for "parallel motion direction
      selectivity" and discuss its implications for the motion streak hypothesis. Taken
      as a whole, we find that the measured response properties of cortical neurons to
      moving spot and plaid patterns agree with the recent psychophysics and support
      the hypothesis that motion streak signals are present in V1.

PMID- 11829298
TI  - A cGMP-gated channel subunit in Limulus photoreceptors.
AB  - The phototransduction cascade in invertebrate photoreceptors has not been fully
      elucidated. It has been proposed that in Limulus ventral photoreceptor cGMP is
      the intracellular second messenger that directly controls the gating of the light
      dependent channels (Johnson et al., 1986: Bacigalupo et al., 1991). Recently, a
      putative cGMP-gated channel cDNA, Lcng1, has been cloned from Limulus and shown
      to be expressed in the brain and the ventral eye (Chen et al., 1999). In this
      study, we sought to more specifically localize the LCNG1 transcript and protein.
      In situ hybridization was used to determine whether the gene is expressed in glia
      or photoreceptor cells in the ventral eye. The results clearly demonstrated that
      Lcngl mRNA is transcribed in the ventral photoreceptors. On Western blots probed
      with a polyclonal antibody raised against the C-terminus of LCNGI, a 100-kDa band
      and an 80-kDa band was labeled in the membrane protein preparations from brain
      and ventral eye, respectively. The labeling of these bands was blocked by
      preabsorption of the antibody with the antigen, indicating the labeling
      specificity. Immunocytochemistry and confocal microscopy were applied to
      investigate the subcellular localization of this antigen. Immunolabeling was
      highly localized in the transducing lobes of ventral eye photoreceptors and
      lateral eye photoreceptors. In both cases, the labeling was associated with
      membrane regions specialized for phototransduction, but the exact pattern
      appeared to be somewhat different in the two eyes. Preabsorption of the antiserum
      with antigen abolished the labeling, confirming specificity. The results lend
      support to the hypothesis that a cGMP-gated channel is directly involved in the
      phototransduction process.

PMID- 11829299
TI  - Cortical mapping of gamma oscillations in areas V1 and V4 of the macaque monkey.
AB  - To characterize the temporal and spatial parameters of gamma activity evoked by
      visual stimuli in areas V1 and V4 of the monkey cortex, we recorded the
      electrocorticogram (ECoG) with an implanted array of 28 and 31 subdural
      electrodes placed over the surface of the operculum in two anesthetized monkeys.
      This intermediate level of recordings should help to bridge the gap between
      multiunit and scalp recordings. Both averaged and single-trial responses to small
      flashed stimuli, for which we varied the retinotopic position, the luminance and
      the color, were analyzed in the time-frequency domain using a wavelet-based
      decomposition of the signal. Large gamma oscillations (40-55 Hz), not phase
      locked to stimulus onset, were observed during the whole stimulus presentation,
      whereas visual evoked potentials (VEPs) were present mainly at stimulus onset and
      offset. Cortical mapping showed that both activities were restricted in spatial
      extent and followed the retinotopic organization of area V1 on the operculum,
      thus strongly suggesting they were generated in the underlying cortex.
      Oscillatory burst detection in single trials showed that one to two bursts
      lasting from 100 ms to 500 ms occurred in the first 500 ms following stimulus
      onset, and that bursts occurring during the subsequent phases of the response had
      a smaller amplitude and duration. Finally, we showed that gamma activity was
      stronger with higher luminances and for red than for green, yellow, or white
      stimuli of same luminance. In one animal we recorded gamma activity over area V4.
      This was of lower magnitude than the activity recorded over V1 and was delayed by
      40 ms with respect to the beginning of gamma activity in V1, in contrast with the
      VEPs that were delayed by 20 ms only. Both gamma oscillations and early VEP
      followed the retinotopic organization of V4 over the prelunate gyrus. The results
      show that gamma oscillations are dependent upon the same parameters as the VEPs
      (retinotopic position, luminance, and color). However, the differences in the
      time course of VEPs and gamma activity (transient vs. sustained) suggests that
      these two responses may reflect different cell populations, different networks,
      or different firing modes.

PMID- 11829300
TI  - Encoding of both vertical and horizontal disparity in random-dot stereograms by
      Wulst neurons of awake barn owls.
AB  - In binocular vision, the lateral displacement of the eyes gives rise to both
      horizontal and vertical disparities between the images projected onto the left
      and right retinae. While it is well known that horizontal disparity is exploited
      by the binocular visual system of birds and mammals to enable depth perception,
      the role of vertical disparity is still largely unclear. In this study, neuronal
      activity in the visual forebrain (visual Wulst) of behaving barn owls to vertical
      disparity was investigated. Single-unit responses to global random-dot
      stereograms (RDS) were recorded with chronically implanted electrodes and
      transmitted via radiotelemetry. Nearly half of the cells investigated (44%,
      16/36) varied the discharge as a function of vertical disparity. Like horizontal
      disparity tuning profiles, vertical-disparity tuning curves typically exhibited
      periodic modulation with side peaks flanking a prominent main peak, and thus,
      could be fitted well with a Gabor function. This indicates that tuning to
      vertical disparity was not caused by disrupting horizontal-disparity tuning via
      vertical stimulus offset, but by classical disparity detectors whose orientation
      tuning was tilted. When tested with horizontal in addition to vertical disparity,
      almost all cells investigated (92%, 12/13) were tuned to both kinds of disparity.
      The emergence of disparity detectors sensitive in two dimensions (horizontal and
      vertical) is discussed within the framework of the disparity energy model.

PMID- 11829302
TI  - Development of cholinergic amacrine cell stratification in the ferret retina and
      the effects of early excitotoxic ablation.
AB  - The present study has examined the emergence of cholinergic stratification within
      the developing inner plexiform layer (IPL), and the effect of ablating the
      cholinergic amacrine cells on the formation of other stratifications within the
      IPL. The population of cholinergic amacrine cells in the ferret's retina was
      identified as early as the day of birth, but their processes did not form
      discrete strata until the end of the first postnatal week. As development
      proceeded over the next five postnatal weeks, so the positioning of the
      cholinergic strata shifted within the IPL toward the outer border, indicative of
      the greater ingrowth and elaboration of processes within the innermost parts of
      the IPL. To examine whether these cholinergic strata play an instructive role
      upon the development of other stratifications which form within the IPL, one-week
      old ferrets were treated with L-glutamate in an attempt to ablate the population
      of cholinergic amacrine cells. Such treatment was shown to be successful,
      eliminating all of the cholinergic amacrine cells as well as the alpha retinal
      ganglion cells in the central retina. The remaining ganglion cell classes as well
      as a few other retinal cell types were partially reduced, while other cell types
      were not affected, and neither retinal histology nor areal growth was compromised
      in these ferrets. Despite this early loss of the cholinergic amacrine cells,
      which are eliminated within 24 h, other stratifications within the IPL formed
      normally, as they do following early elimination of the entire ganglion cell
      population. While these cholinergic amacrine cells are present well before other
      cell types have differentiated, apparently neither they, nor the ganglion cells,
      play a role in determining the depth of stratification for other retinal cell
      types.

PMID- 11829301
TI  - N-cholinergic facilitation of glutamate release from an individual retinotectal
      fiber in frog.
AB  - Nicotinic acetylcholine receptors are localized on retinotectal axons' terminals
      in lower vertebrates. The effects of activation of these receptors by endogenous
      acetylcholine were observed under stimulation of mass optic fibers. This study
      was designed to determine whether endogenous acetylcholine facilitates frog
      retinotectal transmission, provided only the synapses of an individual optic axon
      are activated, and to evaluate the feasible extent of nicotinic facilitation in
      these synapses by applied agonist. To this end, the effects of cholinergic drugs
      on the extracellular action and synaptic potentials recorded from the terminal
      arborization of a separate retinotectal fiber (in layer F of the tectum) were
      investigated in vivo. Glutamatergic nature of retinotectal synapses was
      reexamined by treatment with kynurenic acid. Both kynurenic acid (0.25-1 mM) and
      d-tubocurarine chloride (10-15 microM) significantly depressed the synaptic
      potentials. Carbamylcholine chloride (50-150 microM) evoked a large augmentation
      of the synaptic potentials and a slight but statistically significant decrease of
      the action potentials. D-tubocurarine reduced the effect of carbamylcholine.
      Pilocarpine hydrochloride (50 microM) had only a weak effect. The paired-pulse
      facilitation of the synaptic potentials changed significantly under the action of
      carbamylcholine and d-tubocurarine. The obtained results suggest that the
      glutamate release from activated synapses of individual retinotectal axons is
      facilitated by endogenous acetylcholine via presynaptic nicotinic receptors.
      Under used stimulation conditions, this modulation mechanism was employed only
      partially since its activation by applied carbamylcholine could enhance synaptic
      transmission up to 2.8 times.

PMID- 11829303
TI  - Retinal acetylcholine content in normal and myopic eyes: a role in ocular growth
      control?
AB  - Retinal neurotransmitters are known to play a role in postnatal ocular
      development and eye growth. The success of muscarinic antagonists in blocking
      form-deprivation myopia has implicated retinal acetylcholine in the control of
      ocular growth. The present study investigated whether steady-state content of
      acetylcholine (ACh) and its metabolite choline (Ch) are altered in the retina of
      eyes developing axial myopia, in both tree shrews and chicks. Retinal ACh and Ch
      content were measured using reverse-phase high-performance liquid chromatography.
      Posterior and anterior retinal samples were analyzed from myopic (form deprived)
      and control eyes as well as age-matched normal eyes. Normative data on retinal
      neurotransmitter content demonstrated that chick retinas contained less than half
      the ACh and Ch neurotransmitter content of tree shrews when normalized to retinal
      protein (ACh: 61 +/- 3 vs. 130 +/- 6 ng, Ch: 131 +/- 5 vs. 347 +/- 25 ng). There
      was no significant difference in either ACh or Ch content between myopic and
      contralateral control eyes in either tree shrews or chicks, irrespective of the
      degree of myopia. This finding was consistent for both posterior, anterior, and
      consequently whole retinal samples. In contrast, dopamine and DOPAC contents were
      found to be reduced in myopic compared to control eyes of the same tree shrews
      (dopamine -6.9% and DOPAC -15.5%) and chicks (dopamine -12.3% and DOPAC -28.2%).
      These findings demonstrate that, contrary to dopamine and DOPAC content, steady
      state retinal acetylcholine and choline content is not significantly altered
      during myopia development.

PMID- 11829304
TI  - Effects of light adaptation on contrast processing in bipolar cells in the
      retina.
AB  - Effects of light adaptation on contrast processing in the outer retina were
      investigated over nearly four decades of background illumination by analyzing the
      intracellular responses of 111 bipolar cells, 66 horizontal cells, and 22 cone
      photoreceptors in the superfused eyecup of the tiger salamander (Ambystoma
      tigrinum). Light adaptation had striking and similar effects on the average
      contrast responses of the hyperpolarizing (Bh) and depolarizing (Bd) classes of
      bipolar cells: Over the lower two decades of background illumination, the
      contrast gain increased 7-fold to reach values as high as 20-30, the dynamic
      range and the half-maximum contrast decreased by about 60%, the total voltage
      range increased some 40%, and contrast dominance changed from highly positive to
      more balanced. At higher levels of background, most aspects of the contrast
      response stabilized and Weber's Law then held closely. In this background range,
      the contrast gain of bipolar cells was amplified some 20X relative to that of
      cones whereas the corresponding amplification in horizontal cells was about 6X.
      Differences in the growth of contrast gain with the intensity of the background
      illumination for cones versus bipolar cells suggest that there are at least two
      adaptation-dependent mechanisms regulating contrast gain. One is evident in the
      cone photoresponse such that an approximately linear relation holds between the
      steady-state hyperpolarization and contrast gain. The other arises between the
      voltage responses of the cones and bipolar cells. It could be presynaptic
      (modulation of cone transmitter release by horizontal cell feedback or other
      mechanisms) and/or postsynaptic, that is, intrinsic to bipolar cells. Contrast
      gain grew with the background intensity by a larger factor in horizontal than in
      bipolar cells. This provides a basis for the widely held view that light
      adaptation increases the strength of surround antagonism in bipolar cells. On
      average, the effects of light adaptation and most quantitative indices of
      contrast processing were remarkably similar for Bd and Bh cells, implying that
      both classes of bipolar cells, despite possible differences in underlying
      mechanisms, are about equally capable of encoding all primary aspects of contrast
      at all levels of light adaptation.

PMID- 11829305
TI  - Metabolic activity in optic tectum during regeneration of retina in adult
      goldfish.
AB  - Retinal and visual function returns following retinal destruction by ouabain in
      adult goldfish (Carassius auratus). Although the precise cellular mechanisms are
      unclear, the ability to regenerate CNS neurons and connections that subsequently
      sustain visual behavior is remarkable, especially for an adult vertebrate. In
      this paper, we ask whether visual stimulation via new retinal cells can activate
      existing cells in the optic tectum, which normally receives the largest retinal
      projection in this species. The right eyes of adult goldfish were injected with
      ouabain. After 1-18 weeks the conscious, freely moving fish were exposed to
      spatially and temporally varying visual stimuli and the resulting tectal
      metabolic activity was determined with the autoradiographic deoxyglucose method.
      In normal controls without lesions, visual stimulation produced equally strong
      metabolic activity in both tectal hemispheres, peaking in the layer where most
      retinotectal projections terminate (N = 6). One week after ouabain injection,
      metabolic activity in the contralateral, deprived tectum was dramatically reduced
      (N = 5), closely resembling the effect of unilateral ocular enucleation (N = 5).
      However, 9-18 weeks after ouabain injection, metabolic activity in the deprived
      tectum recovered to a level that was statistically indistinguishable from normal
      controls (N = 6). These findings suggest that, after a comprehensive cytotoxic
      lesion of the retina, regenerated ganglion cells not only establish new
      connections with the preexisting optic tectum, but also effectively transmit
      visual information they receive from newly generated photoreceptors to the "old"
      tectum.

PMID- 11829306
TI  - Development of postreceptoral function in pigmented and albino guinea pigs.
AB  - Retinal neurons are generated in overlapping growth spurts with ganglion cell and
      cone populations peaking sooner than rod and bipolar cell numbers. As such the
      functional development of the inner and outer retinal components and elements
      within these strata (rods vs. cones) may differ. We considered the postnatal
      development of the postreceptoral components of the ERG (P2, oscillatory
      potentials) in the guinea pig. ERGs were also evaluated across albino and
      pigmented strains in order to consider the role that pigmentation has for
      functional development. Electroretinograms were collected on postnatal days PDI
      to PD60 (n = 4-7 per time point). The postreceptoral P2 amplitude and implicit
      time was extracted (digital subtraction of modelled P3 and filtering, 0.5-49 Hz).
      Intensity-response relationships were described using Naka-Rushton functions
      whose parameters were compared using a nonparametric bootstrap. Oscillatory
      potentials (OPs) were extracted following signal conditioning and filtering to
      remove the a- and b-waves and were described using a Gabor function. OP response
      parameters were compared using repeated measures ANOVA. Postreceptoral P2
      amplitudes mature soon after birth (PD10-PD12). Oscillatory potentials show a
      similar postnatal amplitude development (PD10-PD12) but a later maturation in
      timing (PD20) compared with the postreceptoral waveform. All components (P3, P2,
      and OPs) declined at the same relative rate with age after PD12. Albino animals
      gave larger, faster, and more sensitive waveforms at all ages but showed the same
      age-related trends as did pigmented animals. Early development of inner retinal
      synapses in guinea pigs may underlie the rapid postnatal maturation of their
      postreceptoral response. These appear to be constrained by the development of
      receptoral responses. All components declined at the same rate suggesting either
      a change in the photoreceptoral response or changes to ocular impedance with age.

PMID- 11829307
TI  - Transgenic expression of the jellyfish green fluorescent protein in the cone
      photoreceptors of the mouse.
AB  - The goal of this study was to determine whether the jellyfish green fluorescent
      protein (GFP) could be used in transgenic mice to label and purify cone
      photoreceptors from the living retina. We created a transgene containing the 5'
      regulatory sequence of the human red pigment gene (pR6.5 lacZ clone; kindly
      provided by J. Nathans & Y. Wang), fused to the GFP coding sequence. This
      transgene was used to generate seven lines of PCR-positive founders. Three of the
      lines had bright green fluorescent cone photoreceptors. The GFP fills the entire
      cell. Two mouse lines had only a few (-10-100) fluorescent cells per retina, and
      one line (R6.85933) had many thousands. In the latter, double labeling of the
      cones with RITC-conjugated peanut agglutinin reveals that in the ventral retina a
      small proportion of the cones express GFP, while in the dorsal retina the
      majority do. Cells dissociated from the retinae of line R6.85933 continue to
      fluoresce and can be readily detected and enriched with flow cytometry. The
      signal provides a log unit of separation between the fluorescent cone soma and
      the remaining retinal cells. Roughly 3% of the cells are this fluorescent, and it
      is possible to purify up to 30,000 cells from one mouse. RT-PCR analysis of the
      mRNA from these isolated cells detects both the middle and short wavelength
      opsins with little if any contamination from rhodopsin.

PMID- 11829308
TI  - Inhibitors of guanylate cyclase inhibit phototransduction in limulus ventral
      photoreceptors.
AB  - The second messenger systems involved in the final stages of the
      phototransduction cascade in Limulus photoreceptors remain unclear. Excised
      patches of transducing membrane contain cGMP-gated channels, suggesting the
      involvement of cGMP in the excitation process. To further explore this
      possibility, we tested the effects of inhibitors and agonists of guanylate
      cyclase. The active site cyclase inhibitors guanosine 5'-tetraphosphate and
      adenosine 5'-tetraphosphate produced a reversible reduction of the response to
      light without affecting resting membrane properties. The cyclase inhibitor Rp
      GTPalphaS produced a similar reduction, but the effect was only slightly
      reversible. The reduction in the response produced by these inhibitors was
      robust, often producing over a 95% decrease in the amplitude of the light
      response. Previous work had shown that an end-product cyclase inhibitor,
      imidodiphosphate, also inhibited the response. The consistent results with four
      different guanylate cyclase inhibitors strongly support the involvement of this
      enzyme in the phototransduction cascade. To determine whether the guanylate
      cyclase involved is the NO-dependent soluble form, we applied inhibitors and
      activators of the nitric oxide synthase/guanylate cyclase pathway such as L-N5-(1
      iminoethyl) ornithine, sodium nitroprusside, and carboxy-PTIO. None of these
      agents had any substantial effect on phototransduction. Taken together, these
      results support a role for a particulate guanylate cyclase in Limulus
      photoreceptor excitation.

PMID- 11829309
TI  - Transneuronal retrograde transport of attenuated pseudorabies viruses within
      central visual pathways.
AB  - Pseudorabies virus (PRV) has been shown to be an effective transneuronal tracer
      within both the peripheral and the central nervous system. The only
      investigations of this virus in the visual system have examined anterograde
      transport of PRV from injection sites in the retina. In the present study, we
      injected attenuated forms of PRV into the primary visual cortex of both rats and
      cats to determine whether transneuronal retrograde infection would occur back to
      the retina. In rats, we made small injections into visual cortex of a strain of
      PRV (Bartha Blu) that contained a beta-galactosidase promoter insert. In cats, we
      injected PRV-M201 into area V1 of visual cortex. After a 2- to 4-day incubation
      period, we examined tissue from these animals for the presence of the beta
      galactosidase marker (rats) or the virus itself (cats). Cortical PRV injections
      resulted in transneuronal retrograde infection of the lateral geniculate nucleus
      (LGN), thalamic reticular nucleus (TRN), and retina. PRV was retinotopically
      distributed in the pathway. In addition, double-labeling experiments in cats
      using an antibody against gamma-aminobutyric acid (GABA) were conducted to reveal
      PRV-labeled interneurons within the LGN and TRN. All TRN neurons were GABA+, as
      was a subset of LGN neurons. Only the subset of TRN neurons adjacent to the PRV
      labeled sector of LGN was labeled with PRV. In addition, a subset of GABA+
      interneurons in LGN was also labeled with PRV. We processed some tissue for
      electron microscopy to examine the morphology of the virus at various replication
      stages. No mature virions were detected in terminals from efferent pathways,
      although forms consistent with retrograde infection were encountered. We conclude
      that the PRV strains we have used produce a local infection that progresses
      primarily in the retrograde direction in the central visual pathways. The
      infection is transneuronal and viral replication maintains the intensity of the
      label throughout the chain of connected neurons, providing a means of examining
      detailed circuitry within the visual pathway.

PMID- 11829310
TI  - Absolute and relative sensitivity of the scotopic system of rat:
      electroretinography and behavior.
AB  - The goal of the present study was to relate the dark and light-adapted flash
      sensitivity of the scotopic threshold response (STR) and rod b-wave of the
      electroretinogram (ERG) to behaviorally measured rod increment threshold
      responses. Small amplitudes of the dark-adapted STR and b-wave, the latter after
      application of NMDA, were found to increase in proportion to flash intensity. The
      value obtained for the sensitivity of the b-wave would be expected if signals
      from rods were summed linearly by the rod bipolar cell. The sensitivity of the
      STR could not be accounted for in terms of rod signal convergence as the source
      of this ERG component is still unknown. Increment threshold responses of rats
      were measured behaviorally in an operant conditioning chamber. At absolute
      threshold, on average I in 2400 rods were activated by the test flash. Comparison
      of the adaptive effects of background lights on behaviorally measured scotopic
      sensitivity and rod ERG sensitivity suggest that the increment threshold
      sensitivity of rat is regulated at three different sites in the retina.

PMID- 11829311
TI  - The psychophysical periphery effect crosses the vertical meridian.
AB  - This study measured the periphery effect and compared its magnitude when the
      peripheral stimulation was on the same or opposite side of the vertical meridian
      as the test spot. Test thresholds for a 1.5-deg diameter, 8-ms spot located 1.75
      deg to one side of the vertical meridian were elevated by approximately 0.125 log
      units when a 0.25 cycles/deg (cpd) counterphased grating was presented at a
      similar eccentric offset on the other side of the vertical meridian. The
      periphery effect disappeared when the test spot was moved outward to 8-deg
      eccentricity. When the grating and test were presented on the same side of the
      vertical meridian, test thresholds at both retinal locations were elevated by the
      same amount, 0.2 log units. Consistent with the physiology in cat retina, the
      periphery effect in humans also crosses over the vertical meridian. However, the
      effect is small and the test spot must be in close proximity to the vertical
      meridian for it to be observed. Also, the crossover periphery effect is reduced
      in magnitude by 37.5% compared to when the grating and test are presented on the
      same side of the vertical meridian. This suggests there may be a difference in
      how the underlying neural mechanism that transmits the periphery effect signal
      laterally is organized for sending the periphery effect signal across the
      vertical meridian as compared to within a retinal hemifield.

PMID- 11829312
TI  - Membrane current of retinal rods of Caudiverbera caudiverbera (Amphibia:
      Leptodactylidae): dark noise, spectral and absolute light sensitivity.
AB  - We investigated the photocurrents from isolated rods of the South American
      anuran, Caudiverbera caudiverbera. Rod outer segments were on average 66.4 +/-
      11.2 microm (mean +/- S.D., n = 104) in length and 6.6 +/- 0.9 microm (mean +/-
      S.D.) in diameter: 40 +/- 22 photoisomerizations (mean +/- S.D., range 10-99, n =
      16) were required for eliciting a half-saturating photocurrent response. The time
      to-peak was 911 +/- 217 ms (mean +/- S.D., n = 14, 20 degrees C) in the linear
      range of the response and the integration time of the current response was 1744
      +/- 451 ms (mean +/- S.D., n = 14). The time-to-peak appears to be slower and the
      integration time shorter in Caudiverbera than in Ambystoma tigrinum, Rana pipiens
      or Xenopus laevis rods under similar experimental conditions. The a-band of rod
      spectral sensitivity has a lambda(max) at 520 +/- 2.1 nm (mean +/- S.D., range
      516-525 nm, n = 24) and the bandwidth fits a porphyropsin visual pigment. The
      single-event response amplitude ranges from 0.31-0.51 pA, depending on the
      calculation method. The intrinsic dark current (variance at dark minus variance
      under bright light) was 0.045 +/- 0.040 pA2 (mean +/- S.D., n = 24). Our results
      support the presence of a dark-noise component below 1 Hz, with kinetics similar
      to the single-photon evoked response and a rate of 0.006 events s(-1) (n = 9).

PMID- 11829313
TI  - Dietary flavonoids and risk of coronary heart disease.
AB  - Flavonoids, a group of phenolic compounds found naturally in fruit, vegetables,
      nuts, flowers, seeds and bark are an integral part of the human diet. They have
      been reported to exhibit a wide range of biological effects, including
      antiischemic, antiplatelet, antineoplastic, antiinflammatory, antiallergic,
      antilipoperoxidant or gastroprotective actions. Furthermore, flavonoids are
      potent antioxidants, free radical scavengers and metal chelators, and inhibit
      lipid peroxidation. Oxidative modification of low-density lipoproteins (LDLs) is
      believed to play a crucial role in atherogenesis. Epidemiological studies have
      shown that the consumption of fruits and vegetables, and regular red wine
      consumption is related with a reduced risk of cardiovascular diseases.

PMID- 11829314
TI  - The mechanism of alloxan and streptozotocin action in B cells of the rat
      pancreas.
AB  - Alloxan and streptozotocin are widely used to induce experimental diabetes in
      animals. The mechanism of their action in B cells of the pancreas has been
      intensively investigated and now is quite well understood. The cytotoxic action
      of both these diabetogenic agents is mediated by reactive oxygen species,
      however, the source of their generation is different in the case of alloxan and
      streptozotocin. Alloxan and the product of its reduction, dialuric acid,
      establish a redox cycle with the formation of superoxide radicals. These radicals
      undergo dismutation to hydrogen peroxide. Thereafter highly reactive hydroxyl
      radicals are formed by the Fenton reaction. The action of reactive oxygen species
      with a simultaneous massive increase in cytosolic calcium concentration causes
      rapid destruction of B cells. Streptozotocin enters the B cell via a glucose
      transporter (GLUT2) and causes alkylation of DNA. DNA damage induces activation
      of poly ADP-ribosylation, a process that is more important for the
      diabetogenicity of streptozotocin than DNA damage itself. Poly ADP-ribosylation
      leads to depletion of cellular NAD+ and ATP. Enhanced ATP dephosphorylation after
      streptozotocin treatment supplies a substrate for xanthine oxidase resulting in
      the formation of superoxide radicals. Consequently, hydrogen peroxide and
      hydroxyl radicals are also generated. Furthermore, streptozotocin liberates toxic
      amounts of nitric oxide that inhibits aconitase activity and participates in DNA
      damage. As a result of the streptozotocin action, B cells undergo the destruction
      by necrosis.

PMID- 11829315
TI  - Microvascular endothelial cells from human omentum lack an inward rectifier K+
      current.
AB  - In most macrovascular endothelial cell (EC) preparations, resting membrane
      potential is determined by the inwardly rectifying K+ current (I(K1)), whereas in
      microvascular EC the presence of I(K1) varies markedly. Cultured microvascular EC
      from small vessels of human omentum were examined by means of the voltage-clamp
      technique to elucidate the putative role of I(K1) in maintaining resting membrane
      potential. Macrovascular EC from human iliac artery and bovine aorta served as
      reference. Human omentum EC showed an outwardly rectifying current-voltage
      relation. Inward current was hardly sensitive to variations of extracellular [K+]
      and Ba2+ block suggesting lack of I(K1). However, substitution of extracellular
      [Na+] and/or [Cl-] affected the current-voltage relation indicating that Na+ and
      Cl- contribute to basal current. Furthermore, outward current was reduced by
      tetraethylammonium (10 mM), and cell-attached recordings suggested the presence
      of a Ca2+-activated K+ current. In contrast to human omentum EC, EC from human
      iliac artery and bovine aorta possessed inwardly rectifying currents which were
      sensitive to variations of extracellular [K+] and blocked by Ba2+. Thus, the lack
      of I(K1) in human omentum EC suggests that resting membrane potential is
      determined by Na+ and Cl- currents in addition to K+ outward currents.

PMID- 11829316
TI  - Slowed inactivation at positive potentials in a rat axonal K+ channel is not due
      to preferential closed-state inactivation.
AB  - We have investigated slow inactivation in a rat axonal K+ channel, the I channel.
      Using voltage steps to potentials between -70 mV and +80 mV, from a holding
      potential of -100 mV, we observed a marked slowing of inactivation at positive
      potentials: the time constant was 4.5+/-0.4 s at -40 mV (mean +/- S.E.M.),
      increasing to 14.7+/-2.0 s at +40 mV. Slowed inactivation at positive potentials
      is not consistent with published descriptions of C-type inactivation, but can be
      explained by models in which inactivation is preferentially from closed states
      (which have been developed for Kv2.1 and some Ca2+ channels). We tested two
      predictions of preferential closed-state models: inactivation should be more
      rapid during a train of brief pulses than during a long pulse to the same
      potential, and the cumulative inactivation measured with paired pulses should be
      greater than the inactivation at the same time during a continuous pulse. The I
      channel does not behave according to these predictions, indicating that
      preferential closed-state inactivation does not explain the slowing of
      inactivation we observe at positive potentials. Inactivation of the I channel
      therefore differs both from C-type inactivation, as presently understood, and
      from the inactivation of Kv2.1.

PMID- 11829317
TI  - Ultrastructural distribution of the S100A1 Ca2+-binding protein in the human
      heart.
AB  - Impaired calcium homeostasis and altered expression of Ca2+-binding proteins are
      associated with cardiomyopathies, myocardial hypertrophy, infarction or ischemia.
      S100A1 protein with its modulatory effect on different target proteins has been
      proposed as one of potential candidates which could participate in these
      pathological processes. The exact localization of S100A1 in human heart cells on
      the ultrastructural level accompanied with biochemical determination of its
      target proteins may help clarify the role of S100A1 in heart muscle. In the
      present study the distribution of the S100A1 protein using postembedding
      (Lowicryl K4M) immunocytochemical method in human heart muscle has been
      determined quantitatively, relating number of antigen sites to the unit area of a
      respective structural component. S100A1 antigen sites have been detected in
      elements of sarcoplasmic reticulum (SR), in myofibrils at all levels of sarcomere
      and in mitochondria, the density of immunolabeling at Z-lines being about 3 times
      and at SR more than 5 times higher than immunolabeling of remaining structural
      components. The presence of the S100A1 in SR and myofibrils may be related to the
      known target proteins for S100A1 at these sites.

PMID- 11829318
TI  - Effects of pleuran (beta-glucan isolated from Pleurotus ostreatus) on
      experimental colitis in rats.
AB  - The effects of pleuran, beta-1,3 glucan isolated from Pleurotus ostreatus, were
      studied in a model of acute colitis induced by intracolonic administration of
      acetic acid. There was a reduction of the colonic damage score, colonic wet
      weight and wet/dry weight ratio 48 h after single luminal 2% pleuran suspension
      pretreatment. Similar results were obtained after repeated intraperitoneal
      administration of pleuran in doses of 30 and 100 mg/kg. Pleuran given orally as a
      10% food component over 4 weeks was effective in reducing the extent of mucosal
      damage, but did not prevent the increase of myeloperoxidase in the injured
      colonic segment. In the segment without macroscopic evidence of inflammation,
      myeloperoxidase activity was significantly lower as documented by histological
      examination. The results indicate a possible role of this immunomodulator in the
      treatment of ulcerative colitis.

PMID- 11829319
TI  - Genetic variant of luteinizing hormone: impact on gonadal steroid sex hormones in
      women.
AB  - A common variant of the LHbeta subunit has a varying prevalence in various ethnic
      groups. The consequences of the presence of mutated luteinizing hormone (LH)
      concern borderline alterations in pituitary/gonadal function that could be
      mediated by an altered action of variant LH on gonadal steroidogenesis. A
      comparison of plasma concentrations of gonadal steroid sex hormones was completed
      in women heterozygous for variant LH and in women with the wild type of LH in
      three different age ranges. The sample was a randomly selected group of 177
      normal women 16 to 72 years old. Variant LH was determined by immunofluorimetric
      methods using two combinations of monoclonal antibodies. The ratios of LH
      measured by the two assays indicated whether the subject was wild type
      homozygote, heterozygote or homozygote for the variant LHbeta allele. The
      carriers of the variant LH allele in the group of postmenopausal women showed
      higher serum testosterone levels than those with the wild type LH. This is in
      agreement with the clinical observations made previously showing a slightly
      higher androgenic action in the population with variant LH. No differences were
      detected in serum LH, FSH, epitestosterone and sex hormone binding globulin
      (SHBG).

PMID- 11829320
TI  - Serum leptin levels in septic men correlate well with C-reactive protein (CRP)
      and TNF-alpha but not with BMI.
AB  - Leptin, an adipocyte-derived signaling factor, is a member of the IL-6 cytokine
      family. However there is no direct evidence of leptin stimulation of the acute
      phase protein (APP) synthesis which is typical for all other IL-6-like factors.
      The purpose of this study was to characterize the dynamics of circulating leptin
      in relation to ten APPs. We used postoperative septic patients as a model of
      cytokine network hyperstimulation and intensive APP reaction. The prospective
      study was performed on 22 patients with proven postoperative intraabdominal
      sepsis after large abdominal surgery. Plasma levels of leptin, TNF-alpha, IL
      1beta, soluble IL-2 receptor (sIL-2R), IL-6 (ELISA analysis) and ten APPs
      (nephelometric analysis) were estimated. We have demonstrated a statistically
      significant elevation of plasma leptin concentrations in the septic group
      compared with healthy subjects (p<0.001). The correlation of plasma leptin and
      BMI during postoperative sepsis was diminished. The regression coefficient was
      the highest for leptin and CRP (r=0.48, p<0.05), and for leptin and alpha-1
      antitrypsin (r=0.46, p<0.05) in the septic group. There was significant
      correlation between TNF-alpha and leptin (r=0.47, p<0.05) and between IL-6 and
      leptin (r=0.45, p<0.05) in septic patients. No significant correlation was found
      between leptin and "negative" APP and between leptin and IL-1beta. Leptin has
      thus been shown as an acute phase reactant with a potential hematopoietic,
      immunomodulatory and hepatocyte stimulating activity during the infectious and
      non-infectious stress response. The significant correlation between leptin and
      CRP and leptin and alpha-1-antitrypsin indicates that leptin can participate in
      APP synthesis regulation during a systemic inflammatory response.

PMID- 11829321
TI  - Does exogenous melatonin influence the free radicals metabolism and pain
      sensation in rat?
AB  - Melatonin has been shown to play a role in antioxidative defence. We therefore
      studied its effect on oxidative damage to the rat cerebral cortex evoked by
      painful stimulation and immobilization-induced stress. Moreover, the effect of
      melatonin on chronic pain perception was examined. Rats were injected with either
      a high dose of melatonin (100 mg/kg i.p.) or a vehicle for five days and were
      subjected to painful stimulation or immobilization stress 30 min after the
      treatment. To determine the degree of oxidative stress, the levels of free
      radicals, thiobarbituric acid reactive substances (TBARS) as indicators of lipid
      peroxidation and glutathione peroxidase (GSHPx) were estimated in somatosensory
      cortex. Pain perception was measured by the tail-flick and plantar test.
      Melatonin reduced the level of TBARS previously increased by painful stimulation.
      Melatonin also exhibited a slight analgesic effect in those animals exposed to
      painful stimulation but its role in free radical scavenging did not contribute to
      this effect.

PMID- 11829322
TI  - Can primary hyperaldosteronism be considered as a specific form of diabetes
      mellitus?
AB  - Aldosterone-producing adenoma (aldosteronoma)--the most frequent form of primary
      hyperaldosteronism (PH)--is considered a specific form of diabetes mellitus (DM).
      In a previous study we demonstrated insulin resistance in patients with PH. We
      have therefore undertaken a study to evaluate the incidence of abnormalities of
      glucose metabolism in patients with PH (36 subjects) compared to control subjects
      with essential hypertension (EH) (21 patients). The following parameters were
      measured in all studied subjects: office blood pressure (by mercury
      sphygmomanometer in the sitting position), body mass index (BMI), plasma
      potassium, plasma glucose and insulin levels during oral glucose tolerance test
      (OGTT) (0, 60, 120 min), plasma renin activity and plasma aldosterone. Although
      patients with PH tended to have higher stimulated plasma glucose levels after 60
      and 120 min compared to EH, these differences did not attain statistical
      significance. Patients with EH tended to have higher insulin levels at each
      measured interval, but due to a high variability these differences were again not
      significant. There were no significant differences between PH and EH in the
      proportion of diabetics (20% vs. 14%) or patients with impaired glucose tolerance
      (18% vs. 10%). In conclusion, we have found the absence of significant
      differences in the frequency of diabetes mellitus, impaired glucose tolerance and
      insulin resistance in patients with EH and PH. Our data thus do not support the
      idea of primary hyperaldosteronism as a specific type of diabetes mellitus.
      Furthermore, our results indicate that glucose metabolic characteristics in
      essential hypertension and primary hyperaldosteronism tend to be similar. The
      definitive conclusion with respect to the possible causal relationship between DM
      and PH, however, can be obtained only on larger groups of subjects, in particular
      after the evaluation of the effect of surgical/pharmacological treatment of
      primary hyperaldosteronism.

PMID- 11829323
TI  - Acquisition and retrieval of conditioned taste aversion is impaired by brain
      damage caused by two hours of pilocarpine-induced status epilepticus.
AB  - The effect of Cavalheiro's pilocarpine model of epileptogenesis upon conditioned
      taste aversion (CTA), an important example of nondeclarative memory, was studied
      in adult Long Evans rats. Deterioration of CTA was studied during the silent
      period between pilocarpine-induced status epilepticus (SE) and delayed
      spontaneous recurrent seizures. SE was elicited by i.p. injection of pilocarpine
      (320 mg/kg ) and interrupted after 2 hours by clonazepame (1 mg/kg i.p.).
      Peripheral cholinergic symptoms were suppressed by methylscopolamine (1 mg/kg
      i.p.), administered together with pilocarpine. CTA was formed against the salty
      taste of isotonic LiCl. In the experiment of CTA acquisition, the CTA was formed
      and tested during the silent period after SE. In the experiment of CTA retrieval,
      the CTA was acquired before SE and the retrieval itself was tested during the
      silent period. Retrieval of CTA acquired before SE was impaired more than the
      retrieval of CTA formed during the silent period. Our findings indicate that
      epileptic seizures can disrupt even non-declarative memory but that CTA formed by
      the damaged brain can use its better preserved parts for memory trace formation.
      Ketamine (50 mg/kg i.p.) applied 2 min after the onset of pilocarpine-induced
      status epilepticus protected memory deterioration.

PMID- 11829324
TI  - Body, heart, thyroid gland and skeletal muscle weight changes in rats with
      altered thyroid status.
AB  - In the present paper we describe changes of anatomical parameters in inbred Lewis
      strain rats, namely their body weight, body weight gain per week, absolute and
      relative heart, thyroid gland and skeletal muscle weights, that are assumed to
      reflect experimentally altered thyroid status. The hyperthyroid state was induced
      by DL-thyroxine or Na 3,3',5-triiodo-L-thyronine, while methimazole was employed
      for inducing hypothyroidism. We have found that when compared to euthyroid rats,
      hypothyroidism resulted in a significantly lower body weight gain, absolute and
      relative heart weight and, in contrast, in a significant increase of absolute and
      relative thyroid gland weight. On the other hand, hyperthyroidism led to a
      significant increase of absolute and relative heart weight and to a significant
      reduction of absolute and relative thyroid gland weight. However, the body mass
      was not significantly altered in hyperthyroidism as compared with euthyroid rats.
      We conclude that our protocol leads to chronic hyper- or hypothyroidism as
      demonstrated by body, heart and thyroid gland weight changes. These anatomical
      data can thus be utilized as supplemental criteria for the assessment of the
      thyroid state of experimental rats.

PMID- 11829326
TI  - Diminished circadian blood pressure rhythm in patients with asymptomatic
      normotensive pheochromocytoma.
AB  - In our study, the circadian blood pressure (BP) rhythm was studied in subjects
      with asymptomatic and normotensive pheochromocytoma. We have therefore performed
      24-hour BP monitoring not only in 6 subjects with asymptomatic pheochromocytoma,
      but also in 33 patients with symptomatic pheochromocytoma and in 10 normotensive
      subjects, who served as a control group. Circadian BP rhythm was expressed by
      assessing a relative night-time BP decline. We found a similar BP rhythm,
      catecholamine excretion and tumor size in subjects with both forms of
      pheochromocytoma. Subjects with asymptomatic pheochromocytoma had a significantly
      lower night-time systolic BP decline (P=0.01) and diastolic BP decline (P=0.006)
      than normotensive controls. We conclude that the attenuated night-time BP decline
      in normotensive and asymptomatic subjects with pheochromocytoma might be a
      possible sign of partial desensitization of the cardiovascular system to
      catecholamines.

PMID- 11829325
TI  - Gossypol inhibits follicle-stimulating hormone- and epidermal growth factor
      stimulated expansion of oocyte-cumulus complexes from porcine preovulatory
      follicles.
AB  - The role of gossypol in the cumulus expansion of oocyte-cumulus complexes (OCC)
      isolated from large antral porcine follicles was investigated. Marked suppression
      of cumulus expansion stimulated with follicle-stimulating hormone (FSH) and
      epidermal growth factor (EGF) was observed in the presence of different
      concentrations of gossypol. Comparable inhibitory effects were obtained in the
      presence of NO donor, S-nitroso-N-acetylpenicillamine or sodium nitroprusside,
      suggesting that the inhibitory effect of gossypol may be mediated via NO
      generation. The inhibitory effect of gossypol on cumulus expansion of OCC was
      accompanied by inhibition of progesterone secretion of OCC and the decrease of
      [125I]EGF binding to granulosa cells.

PMID- 11829327
TI  - The effect of quercetin on light-induced cytotoxicity of hypericin.
AB  - Protective effect of quercetin, a natural antioxidant compound, on hypericin
      induced cytotoxicity was studied in human promyelocytic leukemia cells (HL-60).
      Hypericin (10(-5) mol x l(-1)) alone significantly decreased cell survival to 21%
      that found in the controls, whereas in combination with quercetin (10(-5) mol x
      l(-1)) this decrease was diminished to 46%. Lower concentrations of quercetin had
      no protective effect. These findings indicate that oxygen radicals can play an
      important role in hypericin-induced phototoxic effects.

PMID- 11829328
TI  - Limb dominance as a potential etiologic factor in noncontact anterior cruciate
      ligament tears.
AB  - A retrospective case series analysis of 80 patients (44 males and 36 females) who
      presented with acute, unilateral, noncontact anterior cruciate ligament (ACL)
      tears was performed. The role of limb dominance as a possible etiologic factor in
      noncontact ACL tears was investigated and the gender-specific relationship was
      determined. Patients were questioned about the nature of their injury and asked
      to list their preferred upper and lower extremities for writing, throwing, and
      kicking-activities previously used to define upper and lower extremity dominance.
      The relationships between limb dominance, side of injury, and gender were
      assessed. Mean patient age was 27.8 years. The left knee was involved in 54% of
      patients and the right knee in 46%. Eighty-nine percent of the study group
      identified themselves as right-hand dominant for writing, 91% were right-hand
      dominant for throwing, and 89% were right-leg dominant for kicking. Overall,
      there was no significant correlation between the side of injury and dominant limb
      for writing (P=.84), throwing (P=.68), or kicking (P=.99). There also was no
      significant gender effect on the relationship between limb dominance and side of
      injury (P=.65). Limited numbers precluded an analysis of specific limb-dominant
      sports activities as potential risk factors. The results of this pilot study
      suggest limb dominance is not a significant etiologic factor for noncontact ACL
      tears.

PMID- 11829329
TI  - Minimally invasive unicondylar arthroplasty: eight-year follow-up.
AB  - This retrospective study reports the senior author's (J.A.R.) results with
      minimally invasive unicondylar knee arthroplasty (UKA). A total of 136 UKAs were
      performed in 1992 for the treatment of unicondylar osteoarthrosis. The surgical
      technique involves a limited medial parapatellar incision that reduces
      perioperative morbidity and bone preparation techniques that emphasize
      preservation of bone for future arthroplasty procedures. At 8 years, 4% of
      Ahlback stage 2 and 3 patients had undergone revision. Minimally invasive UKA
      provides a low morbidity alternative treatment for symptomatic medial compartment
      osteoarthritis.

PMID- 11829330
TI  - Evaluation of clinical factors affecting knee pain after anterior cruciate
      ligament reconstruction.
AB  - This study evaluated clinical factors affecting knee pain after anterior cruciate
      ligament (ACL) reconstruction. One hundred two patients who underwent ACL
      reconstruction were evaluated to determine the incidence of postoperative pain
      and the associated factors affecting this pain. Pain was evaluated according to
      gender, age, length of preoperative period, preoperative pain, meniscal damage,
      cartilage damage at surgery, extension deficit, anterior laxity, and knee
      extension strength. Seventy percent of patients reported pain, and the cause of
      pain varied. Females and older patients indicated a significantly greater degree
      of pain. Cases involving small anterior laxity, highly damaged cartilage, and
      extension deficit indicated a significantly greater presence of pain. Length of
      preoperative period, knee extension strength, and meniscal lesion had no
      correlation with the degree of pain.

PMID- 11829331
TI  - Knee alignment in professional tennis players.
AB  - This study determined lower-limb alignment and knee geometry in professional
      tennis players and compared the data with those from nonathletic individuals.
      Twenty-four radiographs from 12 asymptomatic players (mean age: 23.4+/-3.8 years)
      were prospectively studied. The three angles most useful for describing limb
      alignment and knee geometry in the coronal plane were measured: hip-knee-ankle,
      condylar-hip, and plateau-ankle. The condylar-plateau angle, frontal foot
      rotation angle, and the relationship between the mechanical axis and tibial
      plateau also were calculated. Varus limb alignment was predominant and the
      mechanical axis passed medially through the knee center; there was increased
      valgus inclination of the distal femur, varus angulation of the tibial plateau,
      near parallel alignment of the joint, and exaggerated external foot rotation. Hip
      knee-ankle, condylar-hip, plateau-ankle, and frontal foot rotation angles were
      significantly different (P<.05, two-tailed t test) from previously reported
      angles of nonathletic individuals. Variations, probably due to repetitive dynamic
      demands imposed on lower limbs from an early age, seem to involve both femoral
      condyles and proximal tibial metaphyses, maintaining normal parallel joint
      alignment.

PMID- 11829332
TI  - Bilateral total knee arthroplasty in an achondroplastic dwarf 43 years after
      bilateral tibial osteotomies.

PMID- 11829333
TI  - Steroid-induced osteonecrosis of the femoral condyle in a pediatric patient with
      nephrotic syndrome.

PMID- 11829334
TI  - Synovial tissue and synovial fluid.
AB  - Synovial tissue is a highly specialized tissue that keeps the articular joint
      well lubricated, and at the same time provides nutrients to the articular
      surface. A joint needs a small amount of synovial fluid to work. Although the
      tissue structure is simple, its function is highly sophisticated. Because
      synovial tissue is the target of most autoimmune diseases, joints need to be
      understood in their entirety to create new treatments for such immunological
      disorders.

PMID- 11829335
TI  - Synovial impingement syndrome and dysphoria articularis syndrome of the knee.

PMID- 11829336
TI  - Synovial knee pain arising from chronic inflammatory disorders of the knee.

PMID- 11829337
TI  - Arthroscopic treatment of synovial disorders in the shoulder, elbow, and ankle.
AB  - A wide range of synovial conditions can affect patient function and often respond
      to conservative treatment. However, when symptoms do not respond, arthroscopic
      synovectomy is a useful tool for management. Pigmented villonodular synovitis,
      synovial chondromatosis, rheumatoid arthritis, adhesive capsulitis of the
      shoulder, and ankle impingement are the diseases that most often require
      synovectomy. Arthroscopic management offers the following advantages over open
      synovectomy: a more thorough evaluation of the joint and synovium, better access
      for surgical synovectomy, and decreased postoperative morbidity.

PMID- 11829338
TI  - Principles of arthroscopic surgery.

PMID- 11829339
TI  - Neuronal migration, cerebral cortical development, and cerebral cortical
      anomalies.
AB  - Cerebral cortical malformations are relatively common anomalies identified by
      neuroimaging and pathologically in patients with epilepsy and mental retardation.
      A disruption in neuronal migration during central nervous system development has
      been postulated as the pathogenesis for many of these disorders. Recently, the
      cell migration hypothesis has been proven accurate for lissencephaly, subcortical
      band heterotopia, and periventricular nodular heterotopia. Furthermore, advances
      in cellular and molecular biology have begun elucidating the fundamental
      mechanisms underlying these migration disorders. These data have resulted in
      redefining and recategorizing specific malformations based on their molecular
      genetic abnormality. In this review we shall discuss the current understanding of
      neuronal migration in the developing cerebral cortex, the evaluation of these
      patients, and attempt to describe the pathogenesis for several well-characterized
      human disorders of cell migration.

PMID- 11829340
TI  - Endoplasmic reticulum stress in PLP-overexpressing transgenic rats: gray matter
      oligodendrocytes are more vulnerable than white matter oligodendrocytes.
AB  - Studies dealing with transport of proteins from the oligodendrocyte cell body to
      the myelin sheath reveal the presence of different transport pathways.
      Proteolipid protein (PLP) is synthesized at the rough endoplasmic reticulum (ER)
      and then processed through the Golgi apparatus and transported to the myelin
      membranes. Myelin basic protein (MBP) on the other hand is synthesized locally at
      the ends of cell processes where its messenger RNA is translated on free
      ribosomes. Here we show that in rats that overexpress PLP, impairment of PLP
      transport from the cell body to the processes interferes with the translocation
      of other membrane proteins such as myelin-associated glycoprotein (MAG) and
      myelin oligodendrocyte glycoprotein (MOG), but not with peripherally translated
      MBP. In addition, it also impedes the transport of non-myelin proteins, for
      example the amyloid precursor protein (APP). At the ultrastructural level, the ER
      of these metabolically disturbed oligodendrocytes revealed extreme swelling of
      the cisternae, and immunohistochemistry revealed intense expression of the ER
      chaperone molecule BiP/GRP78 and ER folding enzyme protein disulfide isomerase
      (PDI). These features suggest that these oligodendrocytes, which were found
      exclusively in gray matter areas of the spinal cord, started an unfolded protein
      response while suffering from ER stress. Some of these disturbed oligodendrocytes
      were seen to undergo programmed cell death. These results indicate that gray
      matter oligodendrocyte differ from white matter oligodendrocytes in their
      capacity to stabilize metabolic disturbances by an unfolded protein response.

PMID- 11829341
TI  - Axon loss in the spinal cord determines permanent neurological disability in an
      animal model of multiple sclerosis.
AB  - Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central
      nervous system (CNS). Most patients undergo an initial relapsing-remitting (RR
      MS) course that transforms into a relentless neurodegenerative disorder, termed
      secondary progressive (SP)-MS. Reversible inflammation and demyelination account
      readily for the pattern of RR-MS but provide an unsatisfactory explanation for
      irrevocable decline in SP-MS. Axon loss is thought to be responsible for
      progressive, non-remitting neurological disability during SP-MS. There is
      considerable potential for neuroprotective therapies in MS, but their application
      awaits animal models in which axonal loss correlates with permanent neurological
      disability. In this report, we describe quantitative immunohistochemical methods
      that correlate inflammation and axonal loss with neurological disability in
      chronic-relapsing experimental autoimmune encephalomyelitis (EAE). At first
      attack, CNS inflammation, but not axon loss, correlated with the degree of
      neurological disability. In contrast, fixed neurological impairment in chronic
      EAE correlated with axon loss that, in turn, correlated with the number of
      symptomatic attacks. As proposed for MS, these observations imply a causal
      relationship between inflammation, axon loss, and irreversible neurological
      disability. This chronic-relapsing EAE model provides an excellent platform for 2
      critical objectives: investigating mechanisms of axon loss and evaluating
      efficacy of neuroprotective therapies.

PMID- 11829342
TI  - Morphological and biochemical correlations of abnormal tau filaments in
      progressive supranuclear palsy.
AB  - Progressive supranuclear palsy (PSP) is characterized by specific filamentous tau
      inclusions present in 3 types of cells including oligodendrocytes (coiled
      bodies), astrocytes (tufted astrocytes), and neurons (neurofibrillary tangles;
      NFTs). To correlate the morphological features and biochemical composition of tau
      in the inclusions, we examined tau filament-enriched fractions isolated from
      selected brain regions. Frontal and cerebellar white matter manifested a
      predominance of coiled bodies. The isolated fractions contained straight, 14-nm
      wide filaments of relatively smooth appearance. Caudate nucleus and motor cortex
      with numerous tufted astrocytes contained mostly straight, but irregular, 22-nm
      wide filaments with jagged contours. Perirhinal cortex and hippocampus, rich in
      NFTs, contained 22-nm-wide filaments that were twisted at 80-nm intervals. Among
      the regions, those with tufted astrocytes showed the most heterogeneity in the
      ultrastructure of filaments. In all regions, isolated filaments were
      immunolabeled with PHF-1, Tau 46, and AT8. Fractions from all regions showed 2
      PHF-1 immunoreactive bands of 64 and 68 kDa, while an additional band of 60 kDa
      was detected in NFT-enriched regions. All fractions, in varying extents, showed
      Tau-1-immunoreactive bands between 45-64 kDa. The results indicate that the 3
      types of PSP tau inclusions vary in the ultrastructure although with some
      overlapping features. Neuronal and glial inclusions also vary in the biochemical
      profile of tau protein. These differences may depend on the metabolism of tau in
      the diseased oligodendrocytes, astrocytes, and neurons.

PMID- 11829343
TI  - Structure of the cerebral cortex in men and women.
AB  - Expanding previous studies of human cerebral cortical sexual dimorphism showing
      higher neuronal densities in males, we investigated whether gender differences
      also exist in the extent of neuropil, size of neuronal somata, and volumes of
      astrocytes. This histo-morphometric study includes select autopsy brains of 6
      males and 5 females, 12 to 24 yr old. In each brain, 86 defined loci were
      analyzed for cortical thickness, neuronal and astrocytic (8 loci) density
      (stereological counts), and neuronal and astrocytic (8 loci) soma size, enabling
      calculations of neuropil and astrocytic volumes. The female group showed
      significantly larger neuropil volumes than males, whereas neuronal soma size and
      astrocytic volumes did not differ. The expanded data confirmed higher neuronal
      densities in males than in females without a gender difference in cortical
      thickness. These findings indicate that fundamental gender differences exist in
      the structure of the human cerebral cortex, with more numerous, smaller neuronal
      units in men and fewer, larger ones in women; they may underlie gender-specific
      abilities and susceptibilities to disease affecting the neocortex. Laterality
      differences between the sexes were restricted to neuronal soma size showing
      significantly larger values in the female group in the left hemisphere. This
      gender difference may support female's right-handedness, language advantage, and
      tendency for bilateral activation patterns.

PMID- 11829344
TI  - Histopathological-molecular genetic correlations in referral pathologist
      diagnosed low-grade "oligodendroglioma".
AB  - Allelic loss of chromosome 1p predicts increased chemosensitivity and better
      survival in oligodendroglial tumors. Clinical testing for 1p loss in
      oligodendroglial tumors at our hospital has allowed us to postulate that certain
      histological appearances are associated with 1p allelic status. Forty-four cases
      received for genetic testing were diagnosed by referring pathologists as pure low
      grade oligodendroglioma. Central neuropathological review divided the series
      equally into 22 cases with classical oligodendroglioma histology and 22 with more
      astrocytic features. Molecular genetic analyses demonstrated 1p loss in 19 of 22
      classic oligodendrogliomas (86%) and maintenance of both 1p alleles in 16 of 22
      gliomas with astrocytic features (73%). No glial fibrillary acidic protein
      positive cell type (gliofibrillary oligodendrocyte, minigemistocyte, cellular
      processes) was associated with 1p allelic status. Fourteen of the 44 cases were
      treated with chemotherapy at tumor progression: 3 "astrocytic" gliomas with 1p
      loss responded to PCV chemotherapy and 2 classic oligodendrogliomas that
      maintained both 1p alleles included a responder and a non-responder. These
      results suggest that histological appearance correctly predicts genotype in
      approximately 80% of low-grade gliomas, but that tumor genotype more closely
      predicts chemosensitivity. As a result, such objective molecular genetic analyses
      should be incorporated into patient management and into clinical trials of low
      grade diffuse gliomas.

PMID- 11829345
TI  - Spontaneous axonal regeneration in rodent spinal cord after ischemic injury.
AB  - Here we present evidence for spontaneous and long-lasting regeneration of CNS
      axons after spinal cord lesions in adult rats. The length of 200 kD neurofilament
      (NF)-immunolabeled axons was estimated after photochemically induced ischemic
      spinal cord lesions using a stereological tool. The total length of all NF
      immunolabeled axons within the lesion cavities was increased 6- to 10-fold at 5,
      10, and 15 wk post-lesion compared with 1 wk post-surgery. In ultrastructural
      studies we found the putatively regenerating axons within the lesion to be
      associated either with oligodendrocytes or Schwann cells, while other fibers were
      unmyelinated. Immunohistochemistry demonstrated that some of the regenerated
      fibers were tyrosine hydroxylase- or serotonin-immunoreactive, indicating a
      central origin. These findings suggest that there is a considerable amount of
      spontaneous regeneration after spinal cord lesions in rodents and that the fibers
      remain several months after injury. The findings of tyrosine hydroxylase- and
      serotonin-immunoreactivity in the axons suggest that descending central fibers
      contribute to this endogenous repair of ischemic spinal cord injury.

PMID- 11829346
TI  - Temporal expression pattern of cerebrovascular endothelial cell alkaline
      phosphatase during human gestation.
AB  - In premature human neonates, immaturity of cerebral vessels can contribute to
      clinical problems such as germinal matrix hemorrhage and white matter damage.
      Afferent cerebral vessels in the brain of term babies express alkaline
      phosphatase (AP), an ectoenzyme located on the surface of endothelial cells.
      Using AP enzyme histochemistry we have examined the cerebrovasculature of
      premature live-born human neonates to determine when cerebral afferent vessels
      begin to express AP. Brains were collected at autopsy and processed for
      histological examination. AP-stained vessel density in the periventricular white
      matter was quantified using digital imaging and automated morphometry. Babies
      born prior to 28 wk gestation display few AP-positive vessels in the
      periventricular white matter, whereas, babies born after 28 wk gestation exhibit
      an AP-positive vascular pattern that resembles the adult pattern. In contrast,
      immunostaining for collagen revealed an extensive vascular network in both early
      and late gestation infants. Our measurements indicate that neonates born prior to
      28 wk gestation are characterized by immature cerebral white matter afferent
      vessels and raise the possibility that the immaturity compromises vascular
      function.

PMID- 11829347
TI  - Accumulation of beta-amyloid precursor protein in axons correlates with CNS
      expression of SIV gp41.
AB  - Axonal damage represented by accumulation of beta-amyloid precursor protein (beta
      APP) develops in numerous central nervous system (CNS) diseases including human
      immunodeficiency virus (HIV) infection. To study the underlying mechanisms of
      axonal damage associated with HIV CNS infection, the amount of axonal beta-APP
      immunostaining in the corpus callosum of 24 simian immunodeficiency virus (SIV)
      infected macaques and 3 control macaques was measured by computerized image
      analysis. The amounts of beta-APP accumulation were then compared with time post
      inoculation, extent and character of CNS inflammation, and viral load in the CNS
      measured by the amount of immunohistochemical staining for the viral
      transmembrane protein gp41. Significant increases over control values were
      present in 10 of 24 SIV-infected animals. SIV encephalitis was present in 9 of
      the 10 animals with elevated beta-APP Increases in beta-APP correlated most
      strongly with levels of SIV gp41 in the brain (p = 0.005), but significant
      associations with macrophage infiltration and microglial activation (p = 0.04)
      and infiltration by cytotoxic lymphocytes (p = 0.05) also were identified. These
      data demonstrate that beta-APP accumulation in the white matter of SIV-infected
      macaques develops during SIV infection in close correlation with levels of viral
      replication and may serve as a sensitive marker of neuronal/axonal damage
      mediated by viral proteins.

PMID- 11829348
TI  - Enhanced expression of NGF receptors in multiple sclerosis lesions.
AB  - The receptor for nerve growth factor (NGF) comprises a 75-kDa (NGFRp75) and a
      tyrosine kinase A (TrkA) subunit. In view of conflicting opinions on the identity
      of glial targets of NGF in human central nervous system (CNS), we examined the
      cellular distribution of both NGF receptor subunits in normal CNS and in chronic
      multiple sclerosis (MS) lesions. For this, we compared the pattern of recognition
      of 2 monoclonal antibodies (mAbs) and a polyclonal antiserum to NGFRp75. Only the
      2 mAbs specifically recognized NGFRp75, while the polyclonal antiserum showed
      widespread reactivity. In normal CNS and silent MS lesions, immunohistochemistry
      with anti-NGFRp75 mAbs and for TrkA revealed perivascular cell reactivity. At the
      edge of chronic active MS lesions, selective NGFRp75 staining was prominent on
      reactive astrocytes, while throughout the lesion, NGFRp75 was expressed on
      microglia/macrophages. The vast majority of mature or precursor oligodendrocytes
      did not express NGFRp75. Both NGF receptors were co-expressed on a subset of
      inflammatory cells. Immunoreactivity for NGFRp75 on glial and immune cells did
      not correlate with the distribution of apoptotic figures, as detected by TUNEL.
      Thus, expression of NGF receptors in active MS lesions suggests a role for NGF in
      regulating the autoimmune response at both immune and glial cell levels.

PMID- 11829349
TI  - Finger-length ratios, sexual orientation and offspring sex ratios.

PMID- 11829350
TI  - Light-triggered pH banding profile in Chara cells revealed with a scanning pH
      microprobe and its relation to self-organization phenomena.
AB  - When exposed to light, Characean cells develop a pattern of alternating alkaline
      and acid bands along the cell length. The bands were identified with a tip
      sensitive antimony pH microelectrode positioned near one end of Chara internode
      at a distance of 50-100 microm from the cell wall. The stage with Chara cell was
      moved along its longitudinal axis at a computer-controlled speed (100 or 200
      microm s(-1)) relative to the pH probe over a distance of 50 mm. Under sufficient
      uniform illumination of the cell (from 100 to 2.5 Wm(-2)), the homogeneous pH
      distribution becomes unstable and a banding pattern is formed, the spatial scale
      of which decreases with the light intensity. If the cell is locally illuminated,
      bands are formed only in the region of illumination. It is shown that the
      inhibition of cyclosis by cytochalasin B leads to the disappearance of the
      banding pattern. The addition of ammonium (weak base) inhibited the banding
      pattern, whereas acetate (weak acid) alleviated the inhibitory effect of ammonium
      and restored the pH banding. A model explaining the observed phenomena is
      formulated in terms of proton concentration outside and bicarbonate concentration
      inside the cell. It contains two diffusion equations for the corresponding ions
      with nonlinear boundary conditions determined by ion transport processes across
      the cell membrane. The model qualitatively explains most of the experimental
      observations. It describes the dependence of the pattern characteristics on the
      light intensity and reveals the role of cyclosis in this phenomenon.

PMID- 11829351
TI  - Parasitoids may determine plant fitness--a mathematical model based on
      experimental data.
AB  - The present paper deals with the problem of enhancement of plant fitness due to
      parasitization of herbivores. The experimental evidence for such situations is
      reviewed. Two mathematical models, plant-herbivore (two trophic) and plant
      herbivore-parasitoid (three trophic) are considered to analyse the experimental
      observations. The effect of environmental fluctuation in the tritrophic system is
      also observed and optimum values of the inaccessible parameters involved in the
      system are estimated for purposes of biological control.

PMID- 11829352
TI  - The interaction of surface geometry with morphogens.
AB  - Expressions are given for the Gauss and Mean curvatures of a surface of thickness
      h. The two curvatures, (K and H), which are given at each point of the middle
      surface, are adequate to describe the surface. The sheet thickness varies with
      position in the middle surface bisecting the apical and basal surfaces. The
      definitions of K and H are in terms of radii of curvature, but such radii are not
      appropriate variables for determining how morphogens in the surface may couple to
      the geometry. More suitable expressions are developed here. Two important
      geometrical constraints must be satisfied, namely the famous Gauss-Bonnet
      theorem, and an inequality stemming from the definition of the two curvatures. It
      is argued that these constraints are of great usefulness in determining the form
      of the coupling of morphogens to the geometry. In particular, when two key
      morphogens suffice to determine surface geometry, explicit expressions are
      suggested to determine both Gauss (K) and Mean (H) curvatures as functions of
      invariant morphogen densities.

PMID- 11829353
TI  - Community dynamics, trade-offs, invasion criteria and the evolution of host
      resistance to microparasites.
AB  - This article discusses the community dynamics of the evolution of host resistance
      to microparasites. We present exact results for a model with an arbitrary number
      of host strains. We show that these results are identical to those inferred on
      the basis of invadability criteria. The long-term behaviour of the model allows
      monomorphism or dimorphism (but no higher polymorphisms). We invoke trade-offs
      between pathogen transmissibility and either host intrinsic growth rate or
      resistance to crowding. In the first case, convexity leads to an ESS, concavity
      to branching points and repellers. In the second, these roles are interchanged.
      We present results for fixed strain distributions and establish parallels with
      results using an adaptive dynamics perspective. We also establish differences.
      For example, if an ESS is "deleted" from the strain distribution, then adjacent
      strain dimorphism is possible. The invadability criteria which we obtain can be
      expressed in terms of geometrical properties of the trade-offs namely, the slopes
      of chords and tangent to the associated function. We speculate that this result
      may have wider applicability than provided by the context of the present work.

PMID- 11829354
TI  - Resource competition determines selection of B cell repertoires.
AB  - Previous experiments with mouse chimeras demonstrated that cellular competition
      for antigen-specific survival signals plays a crucial role in the maintenance of
      the naive B cell repertoire. Transgenic (Tg) B cell populations in these chimeras
      have a shortened lifespan and poor competitive abilities as compared to more
      diverse non-Tg populations in the same mice. We develop a mathematical model to
      investigate the mechanism of B cell competition. The model allows for various B
      cell clones, generated in the bone marrow, to go into the peripheral circulation,
      where they compete specifically for various ligands providing survival signals.
      In the model we also find the observed poor competitive abilities of the Tg
      repertoire. Investigating the nature of the competition in the model, we find
      that most of the competition is "intraspecific" occurring largely within the
      clone of truly Tg B cells, and within the repertoire of leaky Tg and non-Tg B
      cells. This is confirmed by analysing a simplified version of the model, which
      only allows for intraspecific competition, and resembles a simple ecological
      model with density-dependent death. The fact that our model accounts for the
      data, casts doubt on a previous interpretation of the same data arguing that more
      diverse repertoires outcompete repertoires of lower diversity. Here, we conclude
      that most of the data can be explained with intraspecific competition, and
      formulate an experimental prediction that allows one to distinguish between the
      previous interpretation of inter-specific competition between repertoires, and
      the current interpretation of intraspecific competition.

PMID- 11829355
TI  - A bit of sex stabilizes host-parasite dynamics.
AB  - To date, only a few studies have focused on the effects of sex on population
      dynamics. Previous models have typically found that sexual reproduction dampens
      population fluctuations. Although asexual and sexual reproduction are just the
      two endpoints along a continuum of varying rates of sex, previous work has
      ignored the effects of intermediate degrees of sex on population dynamics. Here
      we study the effects of partial sexual reproduction (i.e. sex occurs only every
      few generations or with small probability in each generation) on the coupled
      population dynamics of a Nicholson-Bailey host-parasite model. We show that
      complex dynamics are simplified for high host population growth rates if the
      frequency of sex is sufficiently high in both host and parasite: sex decreases
      fluctuations in population density, and leads to non-chaotic dynamics for
      population growth rates that would result in chaotic dynamics in the absence of
      sexual reproduction. However, the simplification does not increase gradually with
      an increasing frequency of sex but appears abruptly at low-to-intermediate
      frequencies of sex. For some parameter settings, intermediate frequencies of
      sexual reproduction can simplify the dynamics more than lower or higher
      frequencies. Thus, in agreement with earlier results, sexual reproduction
      typically stabilizes complex population dynamics in our models. Additionally, our
      results suggest that low-to-intermediate frequencies of sex may often be as (or
      even more) stabilizing as high frequencies.

PMID- 11829356
TI  - Species orthogonalization.
AB  - We discuss the general formation of complementary behaviors, functions and forms
      in biological species competing for resources. We call orthogonalization the
      related processes on macro and micro-level of a self-organized formation of
      correlations in the species properties. Orthogonalization processes could be, for
      example, easily observed in sympatric speciation, as we show in numerical studies
      carried out with a new population equation. As a practical result, we find that
      the number of species is proportional to the effective richness of resources and
      depends on their history.

PMID- 11829357
TI  - The hyperexponential growth of the human population on a macrohistorical scale.
AB  - A qualitative comparison of human population dynamics with some other biological
      populations growth in free regime is given in this paper along with a
      quantitative description of human population growth in the last 2000 years. It is
      shown that human population growth law is very different from the growth laws of
      other populations: all biological populations grow according to exponential law,
      whereas the human population grows according to hyperexponential law which
      essentially moves ahead of the exponential one. It is found that unlike cell
      populations, the differential equation of rate of human population growth is of
      second order. This phenomenon can be described due to accelerating function which
      grows simultaneously with human population number. An analytical hyperexponential
      equation, which allows to describe dynamics of human population, was obtained.

PMID- 11829358
TI  - On mutualists and exploiters: plant-insect coevolution in pollinating seed
      parasite systems.
AB  - We investigate the coevolution of time of flowering and time of pollinator
      emergence in an obligate association between a plant and an insect that both
      pollinates and parasitizes flowers. Numerical analysis shows that the system in
      general evolves towards a time of flowering different from the time favoured by
      the abiotic environment. The equilibrium towards which the system evolves is a
      local fitness maximum (an ESS) with respect to mutational variation in flowering
      time but, for the insect, it can be a local fitness minimum at which selection on
      mutational variation in the time of insect emergence is disruptive. A consequence
      of evolutionary convergence to a fitness minimum is that pollinators having an
      earlier phenology can coexist with pollinators having a later phenology. Since
      late emerging insects are more likely to encounter and oviposit within previously
      pollinated flowers, their effect on the plant is more exploitative, leading them
      to function as cheaters within the system. Thus, in the long term, pollinators
      and exploiters are likely to be found in stable coexistence in pollinating seed
      parasite systems.

PMID- 11829359
TI  - Synchronous cultures from the baby machine: anatomy of a model.
AB  - The baby-machine system, which produces newborn Escherichia coli cells from
      cultures immobilized on a membrane, was developed many years ago in an attempt to
      attain optimal synchrony with minimal disturbance of steady-state growth. In the
      present article, we describe in some detail a model designed to analyse such
      cells with a view to characterizing the nature and quality of the synchrony in a
      quantitative manner; it can also serve to evaluate the methodology itself, its
      potential and its limitations. The model consists of five elements, giving rise
      to five adjustable parameters (and a proportionality constant): a major,
      essentially synchronous group of cells with ages distributed normally about zero;
      a minor, random component from a steady-state population on the membrane that had
      undergone only very little age selection during the elution process; a fixed
      background count, to account for the signals recorded by the electronic particle
      counter produced by debris and electronic noise; a time-shift, to allow for
      differences between collection time and sampling time; and the coefficient of
      variation of the interdivision-time distribution, taken to be a Pearson type III.
      The model is fitted by nonlinear least-squares to data from cells grown in
      glucose minimal medium. The standard errors of the parameters are quite small,
      making their estimates all highly significant; the quality of the fit is
      striking. We also provide a simple yet rigorous procedure for correcting cell
      counts obtained in an electronic particle counter for the effect of coincidence.
      An example using real data produces an excellent fit.

PMID- 11829360
TI  - Animal flight dynamics I. Stability in gliding flight.
AB  - Stability is as essential to flying as lift itself, but previous discussions of
      how flying animals maintain stability have been limited in both number and scope.
      By developing the pitching moment equations for gliding animals and by discussing
      potential sources of roll and yaw stability, we consider the various sources of
      static stability used by gliding animals. We find that gliding animals differ
      markedly from aircraft in how they maintain stability. In particular, the
      pendulum stability provided when the centre of gravity lies below the wings is a
      much more important source of stability in flying animals than in most
      conventional aircraft. Drag-based stability also appears to be important for many
      gliding animals, whereas in aircraft, drag is usually kept to a minimum. One
      unexpected consequence of these differences is that the golden measure of static
      pitching stability in aircraft--the static margin--can only strictly be applied
      to flying animals if the equilibrium angle of attack is specified. We also derive
      several rules of thumb by which stable fliers can be identified. Stable fliers
      are expected to exhibit one or more of the following features: (1) Wings that are
      swept forward in slow flight. (2) Wings that are twisted down at the tips when
      swept back (wash-out) and twisted up at the tips when swept forwards (wash-in).
      (3) Additional lifting surfaces (canard, hindwings or a tail) inclined nose-up to
      the main wing if they lie forward of it, and nose-down if they lie behind it
      (longitudinal dihedral). Each of these predictions is directional--the opposite
      is expected to apply in unstable animals. In addition, animals with reduced
      stability are expected to display direct flight patterns in turbulent conditions,
      in contrast to the erratic flight patterns predicted for stable animals, in which
      large restoring forces are generated. Using these predictions, we find that
      flying animals possess a far higher degree of inherent stability than has
      generally been recognized. This conclusion is reinforced by measurements of the
      relative positions of the centres of gravity and lift in birds, which suggest
      that the wings alone may be sufficient to provide longitudinal static stability.
      Birds may therefore resemble tailless aircraft more closely than conventional
      aircraft with a tailplane.

PMID- 11829361
TI  - New proposals from the EC with regard to public health.

PMID- 11829364
TI  - The Annual Robert Tiffany Memorial Lecture: June 2000.

PMID- 11829365
TI  - A general overview of the cancer education needs of non-specialist staff.
AB  - The aim of this study was to identify the cancer education needs of non
      specialist staff. A qualitative design was used involving focus groups,
      individual and paired interviews, focusing on specialist staff, non-specialist
      staff and patients. Six key areas were identified where staff indicated a need
      for education and training. These included: (1) an overview of cancer, what it is
      and how it effects patients; (2) treatments and side-effects; (3) communication
      skills; (4) physical and practical issues; (5) care organisation, referral routes
      and staff roles; and (6) death and dying issues. Similarities in the views of
      specialists and non-specialist staff of all disciplines indicated a workforce who
      would benefit from support and training in cancer issues. This is important if we
      are to provide safe and optimal care to patients with cancer at all stages of the
      disease trajectory.

PMID- 11829366
TI  - The impact of travel on cancer patients' experiences of treatment: a literature
      review.
AB  - This literature review aims to identify the impact of travel on cancer patients'
      experiences of treatment. With centralization of cancer services, patients may
      have to travel considerable distances from their homes and families, to receive
      specialist cancer treatment. Centralization of cancer services may have
      advantages in terms of concentrating clinical expertise, enhancing the range of
      ancillary facilities and rationalising the provision of expensive specialist
      equipment, but it is not known to what extent patients are affected by additional
      travel and the prospect of separation from their social networks. A systematic
      literature search using MEDLINE, SSCI, SOCA and PSYCHLIT, identified 11 relevant
      studies from six countries. The review showed a paucity of research on the
      implications of receiving cancer treatment far from home. Most studies can be
      criticised on methodological grounds. The evidence that travel distance and
      difficulty increases psychological distress, and reduces compliance with
      treatment and take up of treatment is largely inconclusive. However, travel to
      cancer treatment is described as inconvenient and a practical hardship for many
      patients. It may be perceived, or experienced as, a barrier to treatment. Future
      studies should evaluate the impact of travel to treatment on quality of life and
      perceived social support.

PMID- 11829367
TI  - Cancer Information Services: a pre-/post-evaluation of training to promote
      nationwide consistency of information.
AB  - The object of this study was to evaluate whether an integrated training package
      improved the consistency and accuracy of advice about breast cancer to callers of
      Cancer Information Services (CIS) in Australia. The study followed a pre-/post
      evaluation design and the participants were all CIS officers from the state-based
      CIS. A computerized database was used which contained the current best advice
      about breast cancer combined with a 1-day interactive training workshop for all
      officers of participating CIS. The proportion of responses that accorded with
      predetermined model answers for each of five scenarios employed by simulated
      callers during normal working hours at pre-and post-evaluation were then
      calculated. There were 95 simulated calls during pre-evaluation, and 104 calls
      post-evaluation. In some cases, such as breast reconstruction, accordance with
      model answers was high at both pre- and post-test. The proportion of responses on
      an item that related to a description of lymphoedaema differed from pre-to post
      test with P = 0.007; while an item on the appropriateness of discussing genetic
      testing with general practitioners differed from pre-to post-test with P = 0.003.
      There was less concordance, both pre- and post-test, for issues related to
      surgery, hospitalization, familial aspects and Tamoxifen. We concluded that the
      intervention presents a method of disseminating consistent information across a
      number of independent CIS. Some areas were identified that require more targeted
      intervention.

PMID- 11829368
TI  - An evaluation of a cancer counselling service.
AB  - The CancerBACUP London Counselling Service offered short-term face-to-face
      counselling to self-referred cancer patients and their relatives and friends,
      provided by experienced supervised counsellors working within a humanistic
      theoretical framework. This study aimed to identify its clients' characteristics,
      use of the service, extent of perceived benefits and satisfaction with the
      service. Sociodemographic data were collected in Data Sheets from all 384 clients
      who booked an appointment over 18 months; they were predominantly female, < 50
      years old and from non-manual social classes. Significantly more people in those
      classes and in the 30-59 age group attended three or more sessions. Three hundred
      and nine clients who attended at least once were sent an Evaluation Form; 142
      responded. The probability of the Evaluation Forms' return was greater for those
      who had completed more sessions; the great majority of respondents felt that they
      had benefited, and were satisfied with the service. This study, notwithstanding
      its limitations, shows that a short course of counselling may be perceived by
      clients to be helpful; it also raises other issues of value to those involved in
      cancer services and/or counselling provision.

PMID- 11829369
TI  - Cancer and men from minority ethnic groups: an exploration of the literature.
AB  - The authors reviewed literature which has been published in the last 20 years.
      Cancer is the second leading cause of death in developed countries and is
      expected to become a significant cause of death in developing countries. Whilst
      there are a large number of studies on cancer and men, there is a paucity of data
      on men from minority ethnic groups. In the USA, African Americans are more likely
      to develop cancer than any other ethnic group. Although cancer rates amongst
      minority ethnic groups in the UK are thought to be low, 11% of Indian and African
      men and 19% of Caribbean men died from cancer during 1979-1983. There is also
      further evidence in the USA that African American, Filipinos and Native Americans
      have the lowest cancer survival rates. Service utilization, especially tertiary
      care, is also thought to be low amongst minority ethnic groups from the USA and
      the UK. Reasons for these variations include artefactual, cultural, materialist
      and social selectivist explanations as well as the effects of migration, racism
      and genetic disposition. This area is under-researched, in particular cultural
      beliefs about cancer. Further research into this area should apply culturally
      competent methods to ensure valid data to inform cancer policy, education and
      practice.

PMID- 11829370
TI  - A pilot study of the use of progressive muscle relaxation training in the
      management of post-chemotherapy nausea and vomiting.
AB  - The aim of this pilot study was to assess the effectiveness of using progressive
      muscle relaxation training (PMRT) in the management of chemotherapy-related
      nausea and vomiting in Chinese breast cancer patients receiving doxorubicin and
      cyclophosphamide as well as feasibility issues for a larger study. Eight patients
      were randomly assigned to receive either oral anti-emetics as per hospital
      protocol (maxolon) or adjuvant PMRT. Both groups, however, received intravenous
      anti-emetics half an hour before the chemotherapy administration. PMRT was given
      by a trained nurse once a day for 5 days. A repeated measures design was used.
      Nausea and vomiting were assessed with the Morrow Nausea and Vomiting Scale.
      Results indicated that the duration and intensity of nausea were lower in the
      experimental group, although the former was at a borderline level of
      significance. The duration and intensity of vomiting were also lower in the
      experimental group. Delayed nausea and vomiting was observed in both groups.
      Despite the small sample size, the study showed that PMRT is an effective
      adjuvant method to decrease nausea and vomiting in chemotherapy patients. This
      has implications for nursing practice, as it is a low-cost and easy-to-leam
      technique that can be incorporated in the care planning of patients receiving
      chemotherapy.

PMID- 11829371
TI  - Metastatic breast cancer in pregnancy: first case of chemotherapy with docetaxel.
AB  - The focus of this paper is a case study of a woman in the first trimester of
      pregnancy who presented with metastatic breast cancer. The bony spread of the
      metastases was rapid and it was necessary to treat the patient as soon as
      possible after the period of organogenesis (days 18-60 of human gestation). This
      stage is the phase of greatest sensitivity of teratogens and the malformations
      are observed most often. Yet, the choice of third-line chemotherapy was difficult
      because of anthracycline-resistant metastatic breast cancer. The world literature
      reported cytotoxic combinated regimens as the standard of care for the management
      of the metastases. The development of new antitumoral strategies with less
      toxicity and their encouraging results led us to the approval of docetaxel for
      the treatment of the patient even though it had never been tested in pregnancy.
      Docetaxel is a potent inhibitor of microtubule depolymerization and has a unique
      ability to alter certain classes of microtubules. The monochemotherapy was
      administered once every 3 weeks for a total of three cycles until 30 weeks of
      gestation. During the 32nd week of pregnancy the patient delivered a female
      infant whose birthweight and Apgar score were normal. The infant did not have any
      anomalies. The woman finished her treatment in puerperium and she received three
      cycles of docetaxel. The patient has been receiving vinorelbine (one cycle every
      2 weeks) for 2 years; her last follow-up was good and showed that the progression
      of the metastases had stopped. The daughter's psychophysical development was
      normal.

PMID- 11829372
TI  - Information provision to cancer patients: a practical example of identifying the
      need for changes in practice from the Dorset Cancer Centre.
AB  - The aim of this study was to produce a patient-centred information strategy based
      on the results of a local survey of cancer patients about the information they
      receive and their information needs. An anonymous patient survey was distributed
      at the Dorset Cancer Centre, Poole Hospital, the regional cancer centre for
      Dorset, in the South-west of England. All patients attending the Cancer Centre
      during 1 week in September 1999 were asked to complete a questionnaire on patient
      experience of the Cancer Centre, information sources, receipt and quality of
      Centre information, and perception of information requirements. Two hundred and
      eighty-two were returned. Most respondents had accessed information from a number
      of sources. Written Cancer Centre information had been given to most patients,
      and was generally perceived to be useful, understandable and timely. However,
      most patients had received information 'all at once', from a single professional
      group, and a notable proportion did not recall discussing it with staff.
      Furthermore, most patients indicated that information should also be provided to
      families and professionals. Seven items of information were selected as valuable
      by the majority of patients, with many others listed. There was a great deal of
      satisfaction with the current content of the patient information provided.
      However, the distribution system was shown to be in need of improvement. A new
      information strategy has been developed in the light of these findings.

PMID- 11829373
TI  - Forum for Applied Cancer Education and Training. Palliative chemotherapy.

PMID- 11829374
TI  - Hair and cancer chemotherapy: consequences and nursing care--a literature study.
AB  - Hair is a body appendage that throughout history has been a symbol of the social,
      cultural and political climate, in addition to connoting religious affiliation.
      Hair loss on the other hand has been associated with a loss of attractiveness,
      individuality, a state of disgrace and illness, in addition to the ageing
      process, death and a loss of sexuality. One of the most common side-effects of
      chemotherapy is hair loss (alopecia). Alopecia can range from sporadic thinning
      of the hair to complete baldness. Several factors may contribute to the severity
      of hair loss including drug, dose and schedule as well as hair care practices.
      Prevention of alopecia has been a focus in the medical and nursing literature
      since the late 1960s. Mechanical, physical and biological measures have been used
      with varying success. The goal of prevention is primarily the reduction of
      patient distress caused by chemotherapy-induced alopecia. Patient reactions to
      alopecia vary and may be dependent on the individual importance of hair,
      prognosis, degree of expected hair loss, the amount of information and
      preparation given, and physical and psychological coping mechanisms. Nurses play
      an important role in assisting the patient to cope with alopecia by giving the
      needed information and teaching self-care strategies to minimize alopecia, cope
      with alopecia, and protect the skin and eyes following alopecia. These
      interventions are aimed at helping the patient move through a potentially
      devastating experience to a renewed sense of well-being.

PMID- 11829375
TI  - Academia, cancer nursing and a new decade.

PMID- 11829376
TI  - A new paradigm from 10 years of progress.

PMID- 11829377
TI  - Cancer services in the United Kingdom.

PMID- 11829378
TI  - Changing times in cancer care.

PMID- 11829379
TI  - Developing a cancer genetics service in Wales: opinions of gynaecologists on the
      management of women at risk of familial ovarian cancer.
AB  - In Wales, a cancer genetics service has been developing since 1998.
      Gynaecologists play an integral role in the management of women with a family
      history of ovarian cancer and we were interested in investigating referral
      practice and management for relatives of patients with ovarian cancer among
      gynaecologists in Wales. In 1999, a postal questionnaire was sent to all
      gynaecologists. The response rate was 51%. The questionnaire contained structured
      questions about current provision and a number of hypothetical scenarios to
      explore referral patterns to the cancer genetics service. The results of this
      study showed that referrals varied widely among specialists, as did the numbers
      who required onward referral to cancer genetics. The offer of screening to women
      at high risk of ovarian cancer was consistent, although there were variations in
      how often it was offered and the age at which it was offered. Most gynaecologists
      were easily able to establish when it was appropriate to refer onwards to cancer
      genetics, differentiating between women at high or low risk. There was some
      confusion about women at moderate risk of ovarian cancer. This study demonstrated
      the need for clear referral guidelines in Wales. Guidelines have since been
      distributed to all general practitioners and specialists; however, continued
      monitoring and further evaluation of referral practices will be necessary.

PMID- 11829380
TI  - Professional education for the cancer care nurse in England and Wales: a review
      of the evidence base.
AB  - The third European Commission action plan to combat cancer recognized the need to
      develop effective continuing and in-service training programmes for doctors,
      nurses and other healthcare professionals. A literature review and course
      documentary analysis commissioned by the English National Board for Nursing,
      Midwifery and Health Visiting Education (ENB) in 1997 found that, within their
      initial training, nurses in England and Wales are seldom adequately prepared to
      work with cancer sufferers; that very few nurses undertake subsequent specialist
      training in cancer care; that up to half the places available on specialist
      training programmes remain unfilled at any one time; and that, 3 months after
      such training, studies showed that competence has again decreased. As post
      qualifying continuing and in-service education for nurses in their specialist
      areas is not yet mandatory in the UK, it is unlikely that the objectives of the
      European Commission's third action plan or those of successive British
      governments, in successfully combating cancer, will be achieved.

PMID- 11829381
TI  - Improvement in quality of life for cancer patients treated with epoetin alfa.
AB  - Anaemia is a common complication of cancer and cancer therapies, and fatigue is
      one of the most common symptoms of anaemia, disrupting functional performance and
      reducing overall quality of life. The positive effects of treating renal patients
      with recombinant human erythropoietin are well documented. This case report
      series details the specific effects of fatigue on individual patients with cancer
      and their way of life, and describes their significant improvement in lifestyle
      following the reversal of anaemia using recombinant human erythropoietin, epoetin
      alfa.

PMID- 11829382
TI  - Indications of change in life perspective among women with breast cancer admitted
      to complementary care.
AB  - In this study, qualitative content analysis was used in order to understand the
      reported changes of life perspective in interviews with 59 women with breast
      cancer who were admitted to complementary care. The aim of this research was to
      study women's perceived consequences as well as perceived causes of breast cancer
      and to explore aspects of importance to the women. The material was collected in
      semistructured interviews from women with breast cancer at different stages of
      the disease. The women received complementary care at an anthroposophic clinic in
      Sweden. Findings showed that these women's view of their relationships with
      others grew more valuable. Their self-confidence and experience of strength
      improved, and they regarded life as being more enriched. A change in their
      disposition towards becoming more fragile and low-spirited was experienced as a
      hardship by the women. An interesting finding was that the patients described the
      aetiology of the disease from several interacting perspectives, which also
      affected their ideas of how to achieve well-being and health. The findings
      support the view that changes of both benefit and harm are present in the
      experience of breast cancer.

PMID- 11829383
TI  - The knowledge and attitudes of surgical staff towards the use of opioids in
      cancer pain management: can the Hospital Palliative Care Team make a difference?
AB  - The principles of cancer pain management are well established, but evidence
      suggests that these are not incorporated into daily practice and patients are
      still in pain. Deficiencies in knowledge and inappropriate attitudes towards the
      use of opioids may partially explain why the management of cancer pain is still
      such a widespread problem. This study assessed the knowledge and attitudes of 135
      nursing and medical staff working in a surgical unit, before and after working
      with a newly established Hospital Palliative Care Team. The baseline survey
      highlighted the existence of a number of myths and misconceptions in relation to
      opioid use. Results of the follow-up survey indicated that the knowledge and
      attitudes of doctors and nurses had improved after working with the team, but
      that this probably occurred as a result of good working relationships and case
      discussions rather than through formal teaching. The study provided a useful
      method of identifying deficiencies in knowledge and attitude among staff, and
      helped to raise awareness of the problem of cancer pain management. Our challenge
      now is to work with staff to ensure that positive changes in knowledge and
      attitudes are translated into the everyday practice of hospital nurses and
      doctors caring for patients with cancer.

PMID- 11829384
TI  - Forum for applied cancer education and training.

PMID- 11829385
TI  - Periodontal regeneration with an autogenous bone-Bio-Oss composite graft and a
      Bio-Gide membrane.
AB  - This study evaluated the clinical, radiographic, and histologic response to the
      composite use of Bio-Oss porous bone mineral and autogenous bone in combination
      with a Bio-Gide bilayer collagen membrane to achieve regeneration when treating
      human periodontal bone defects. Preoperative recordings for four treatment areas
      included radiographs, clinical probing depths, and attachment levels; these
      recordings were repeated at 9 months. Histologic evaluation revealed new cementum
      with inserting collagen fibers and new bone formation on the surface of both
      types of graft materials. This grafting combination not only compared favorably
      with the previous use of Bio-Oss and Bio-Gide, but exceeded that result with
      almost complete periodontal regeneration. This human histologic study
      demonstrates that autogenous bone in combination with porous bone mineral matrix,
      together with the Bio-Gide collagen membrane, has the capacity to stimulate
      substantial new bone and cementum formation with Sharpey's fiber attachment.

PMID- 11829386
TI  - Alveolar distraction: a possible new alternative to bone grafting.
AB  - Distraction osteogenesis is a new concept to periodontics that may replace the
      more traditional bone grafting techniques of onlay grafts and titanium membrane
      procedures. Distraction osteogenesis is not fraught with the complications of
      graft and membrane exposure or inadequate tissue coverage, which makes the
      distraction procedure an ideal technique to grow unlimited amounts of vertical
      bone height. This article describes a technique to grow new bone and soft tissue
      in a maxillary alveolar defect using a new technique called alveolar distraction
      osteogenesis. A case report is presented of the distraction procedure, reentry 6
      months later, implant placement, and restoration.

PMID- 11829387
TI  - Rationale for the application of the GTR principle using a barrier membrane in
      endodontic surgery: a proposal of classification and literature review.
AB  - Periradicular surgery has become an established treatment option in endodontic
      surgery. The major objective of this surgery is to obtain periradicular tissue
      regeneration, including the formation of a new attachment apparatus, by exclusion
      of any potentially noxious agent within the physical confines of the affected
      root. However, in a substantial number of cases, the endodontic lesion has a
      concomitant marginal periodontal lesion that may complicate the healing success.
      In periodontology, the guided tissue regeneration (GTR) principle using a barrier
      membrane has been extensively studied and successfully used, and thus may become
      an adjunct in endodontic surgery. This article presents a classification system
      of endodontic and periodontal lesions with respect to the application of the
      membrane technique and reviews the pertinent literature based upon this
      classification system.

PMID- 11829388
TI  - Root coverage and papilla reconstruction using autogenous osseous and connective
      tissue grafts.
AB  - Previous studies have reported that the distance from the interdental crest of
      bone to the apical portion of the contact of the two approximating teeth must be
      5 mm or less to support a stable interdental papilla. The reconstruction of a
      stable, long-term papilla for esthetic purposes must therefore consider
      interdental bone reconstruction. Autogenous osseous graft material was harvested
      from the tuberosity and augmented with a subperiosteal connective tissue graft
      for papilla reconstruction between the maxillary central incisors. Flap design,
      osseous graft fixation with a screw, connective tissue placement, wound closure,
      and suturing techniques are presented. To enhance the final result, porcelain
      veneers were bonded to the approximating central incisors. This case report
      demonstrates a surgical procedure that has not been reported to date for papilla
      reconstruction to enhance periodontal esthetics.

PMID- 11829389
TI  - Wide-diameter implants: new concepts.
AB  - At the end of the 1980s, it was suggested that wide-diameter implants be used to
      better the prognosis in cases in which the condition of the supporting bone is
      unfavorable. Technical improvements associated with different shapes and
      materials used for implants have led to an evolution of our concepts of surgical
      and prosthetic treatments. The aim of these new suggestions is to optimize the
      functional and esthetic result while respecting the fundamental principles of
      osseointegration. Up to the present time, very few studies have been published on
      wide-diameter implants. However, the short- and medium-term results that have
      been reported have been very satisfactory.

PMID- 11829390
TI  - Clinical evaluation of anorganic bovine bone xenograft with a bioabsorbable
      collagen barrier in the treatment of molar furcation defects.
AB  - The purpose of this study was to compare Bio-Oss (BO), an anorganic bovine bone
      xenograft, in combination with Bio-Gide (BG), a bioabsorbable collagen barrier,
      to open-flap debridement (OFD) surgery in human mandibular Class II furcation
      defects. A total of 31 furcations (18 treatment, 13 control) in 21 patients were
      treated. There was a statistically significant improvement in most clinical
      indices for the BO/BG group, with minimal improvement noted for the OFD group.
      Vertical probing depth reduction of 2.0 mm and horizontal probing depth reduction
      of 2.2 mm were noted for the BO/BG group, with 0.3 mm and 0.2 mm reductions,
      respectively, noted for OFD. Hard tissue measurements showed 2.0 mm of vertical
      furcation bone fill for BO/BG and 0.5 mm for OFD. The BO/BG group had 3.0 mm of
      horizontal furcation bone fill, and the OFD group had 0.9 mm. The BO/BG group had
      a defect resolution of 82.7%; 42.5% was noted for the OFD group. There was a
      statistically significant difference between BO/BG and OFD in all soft and hard
      tissue measurements with the exception of attachment level, recession, and
      alveolar crest resorption.

PMID- 11829391
TI  - Failure of root coverage of shallow gingival recessions employing GTR and a
      bioresorbable membrane.
AB  - The aim of the present study was to compare the postsurgical outcome of two
      different modes of surgical root coverage of predominantly shallow, Class I or
      II, gingival recessions. Fourteen facial recessions in nine patients were
      subjected to a coronally repositioned flap in combination with a bioresorbable
      membrane, and 14 sites in 13 patients were treated with a connective tissue graft
      employing an envelope technique. Immediately before surgery and after 6 and 12
      months, gingival dimensions as well as root coverage and attachment gain were
      assessed. At baseline, mean recession depths amounted to 2.77+/-1.67 mm and
      2.49+/-1.07 mm for patients treated with a bioresorbable membrane and a free
      connective tissue graft, respectively. Acceptable and stable root coverage of 81%
      to 82% of baseline recession depth and 78% of its width was achieved by grafting.
      In contrast, guided tissue regeneration (GTR) resulted in only 50% coverage of
      recession depth and, after 12 months, only 11% of its width (P < 0.01). Logistic
      regression revealed that the odds of obtaining success, ie, at least 80% root
      coverage, were 3.3 times greater in cases treated with a connective tissue graft
      (P < 0.05). In addition, the odds ratio was 2.3 in cases of recessions below 2.5
      mm compared to deeper recessions and 2 at canines compared to premolars. It was
      concluded that shallow recessions in the 1.5 to 3.5 mm range should not be
      treated with GTR. In these situations, predictable results are achieved with free
      connective tissue grafts employing an envelope technique.

PMID- 11829392
TI  - Hamular frenum modification: a removable denture prosthesis retention and
      stability enhancement.
AB  - A removable denture prosthesis, whether partial or complete, often requires
      preprosthetic surgery to achieve optimum stabilization and retention. While the
      hamular frenum may produce significant dynamic dislodging forces, a literature
      review did not reveal any reports dealing with this problem. A hamular frenum
      reduction surgical procedure using the free autogenous gingival graft procedure
      is described. Prosthetic function may be enhanced by eliminating the dynamic
      disrupting force of the hamular frenum along with improving posterior maxillary
      tuberosity contour and, as necessary, premaxillary form, allowing these contours
      to work in concert to develop a "cupping" stabilizing and retentive complex.

PMID- 11829393
TI  - A perspective on periodontal microsurgery.
AB  - The surgical microscope offers the periodontist increased illumination and visual
      acuity to perform procedures with greater precision than with other methods of
      magnification. This review article outlines the advantages of using smaller
      instruments and sutures, explores the possibility of enhanced calculus removal
      under magnification, and offers suggestions for integrating the microscope into
      periodontal practice.

PMID- 11829394
TI  - Sources of dioxins in the United Kingdom: the steel industry and other sources.
AB  - Several countries have compiled national inventories of dioxin (polychlorinated
      dibenzo-p-dioxin [PCDD] and polychlorinated dibenzofuran [PCDF]) releases that
      detail annual mass emission estimates for regulated sources. High temperature
      processes, such as commercial waste incineration and iron ore sintering used in
      the production of iron and steel, have been identified as point sources of
      dioxins. Other important releases of dioxins are from various diffuse sources
      such as bonfire burning and domestic heating. The PCDD/F inventory for emissions
      to air in the UK has decreased significantly from 1995 to 1998 because of reduced
      emissions from waste incinerators which now generally operate at waste gas stack
      emissions of 1 ng I-TEQ/Nm3 or below. The iron ore sintering process is the only
      noteworthy source of PCDD/Fs at integrated iron and steelworks operated by Corus
      (formerly British Steel plc) in the UK. The mean waste gas stack PCDD/F
      concentration for this process is 1,2 ng I-TEQ/Nm3 based on 94 measurements and
      it has been estimated that this results in an annual mass release of
      approximately 38 g I-TEQ per annum. Diffuse sources now form a major contribution
      to the UK inventory as PCDD/Fs from regulated sources have decreased, for
      example, the annual celebration of Bonfire Night on 5th November in the UK causes
      an estimated release of 30 g I-TEQ, similar to that emitted by five sinter plants
      in the UK.

PMID- 11829395
TI  - Using PCDD/F congener patterns to determine the source of elevated TEQ
      concentrations in cows milk: a case study.
AB  - PCDD/F congener profiles have been used to determine the source of elevated TEQ
      concentrations in cows' milk collected in the vicinity of several industrial
      sites. Principal components analysis and modelling of the air-to-milk transfer of
      individual PCDD/F congeners have shown that the milk fingerprint was related to
      that of sediment taken from the River Rother adjacent to the farm where the cows
      had grazed. It is suggested that sediment from the river had been washed onto the
      grazing land during periods of flooding, and this had been ingested by the
      grazing cows. This pathway could represent an important route of contaminant
      intake for livestock grazing on the regularly inundated floodplains of rivers
      containing contaminated sediments.

PMID- 11829396
TI  - Effects of copper chloride on formation of polychlorinated dibenzofurans in model
      waste incineration in a laboratory-scale fluidized-bed reactor.
AB  - Combustion experiments in a laboratory-scale fluidized-bed reactor have been
      performed to clarify the effects of copper chloride as a catalyst on
      polychlorinated dibenzofurans (PCDFs) formation in municipal waste incineration.
      We used model wastes with and without copper chloride (CuCl2 x 2H2O) as a
      catalyst, both of which contained polyvinyl chloride (PVC) as a chlorine source.
      Combustion temperature was set to 900 degrees C, and the amount of air supplied
      was twice as much as the theoretical amount. The experimental setup had been
      carefully planned to ensure avoidance of the influences of previous experiments.
      Results of these present experiments revealed that copper chloride in the waste
      increased the amount of PCDFs formed and made the homologue profile shifted
      towards the highly chlorinated species. Copper chloride contributes to PCDFs
      formation by promoting chlorination via catalytic reactions, whereby the reaction
      could be important in that organic matters are chlorinated directly by
      chlorinated compounds related to Deacon reaction such as copper chloride. It was
      elucidated that characteristic isomer distribution patterns appeared in case the
      waste contained copper chloride. It is probable in our experiment with copper
      chloride that PCDFs are mainly formed via catalytic reactions of copper compounds
      and carbon.

PMID- 11829397
TI  - Hair analysis: another approach for the assessment of human exposure to selected
      persistent organochlorine pollutants.
AB  - Hair analysis was used for the assessment of exposure to organochlorine
      pollutants in specimens from Greece, Romania and Belgium. A simple method (using
      3 N HCI as incubation reagent, liquid-liquid extraction with hexane/
      dichloromethane (DCM), alumina/acid silica clean-up and GC-ECD/GC-MS analysis)
      was used for screening of specimens. The highest organochlorine load (up to 148
      ng/g hair for the sum of PCB, DDT and hexachlorocyclohexane (HCH) isomers) was
      found in samples from a group of Greek women with past occupational exposure to
      pesticides. DDTs were the main organochlorine pollutants in Greek samples (up to
      70%), while in Belgian hair samples their contribution was reduced to 40%. PCB
      mean concentration was higher in Belgian specimens (up to 14 ng/g hair). Lindane
      (y-HCH) was the main HCH isomer found in the samples (up to 82% in the Greek
      samples). Contribution of p,p'-DDT to the sum of DDTs was higher in Greek samples
      and indicates recent exposure to technical DDT. Similar PCB 153/sum PCBs ratios
      were found for each of the three countries suggesting similar sources of
      pollution with PCBs (mainly dietary). Artificially coloured hair samples were
      found to have lower, but not statistically significant concentrations of
      organochlorine pollutants than the non-coloured hair.

PMID- 11829398
TI  - PCDDs, PCDFs, and PCBs concentrations in breast milk from two areas in Korea:
      body burden of mothers and implications for feeding infants.
AB  - We determined breast milk concentration of polychlorinated dibenzo-p-dioxins
      (PCDDs)/polychlorinated dibenzofurans (PCDFs) and polychlorinated biphenyls
      (PCBs) in 24 mothers living in Korea, and assessed the maternal body burden based
      on PCDDs/PCDFs and PCBs concentrations in breast milk and an infant intake rate
      through breast-feeding based on their concentration in breast milk. PCDDs/PCDFs
      and PCBs levels in breast milk from primipara mothers were found to be higher
      than those from multipara mothers. For total PCDDs/PCDFs TEQ level, 2,3,4,7,8
      PeCDD was the predominant congener, and the proportion of 2,3,7,8-TCDD was less
      than 3% of total PCDDs/PCDFs TEQ level. For PCBs TEQ level, PCB-126 was the
      predominant congener. Maternal body burden levels of PCDDs/PCDFs and PCBs based
      on their concentrations in breast milk were 268-622 TEQ ng. The daily dioxin
      intakes of mothers were predicted to be 0.78-2.18 TEQ pg/kg/day for PCDDs/PCDFs
      and 0.34-0.66 TEQ pg/kg/ day for PCBs. For the first year, the body burden of an
      infant was predicted to be 212 TEQ ng and the daily intake of an infant was
      predicted to be 85 TEQ pg/kg/day, assuming the mean dioxin-related compounds
      concentration (27.54 TEQ pg/g fat).

PMID- 11829399
TI  - Formation of dioxin analogs by open-air incineration of waste wood and by fire of
      buildings and houses concerning Hanshin Great Earthquake in Japan.
AB  - Ash samples were collected from site of open-air incineration and fire concerning
      Hanshin Great Earthquake which occurred in western Japan in the early morning of
      17 January 1995. The average concentrations of total sum of PCDDs, PCDFs and Co
      PCBs in ash collected from wood scrap of broken building fire site, house fire
      site, shoe-making factory fire site and electric appliances store fire site were
      541, 442, 859 and 22,800 pgTEQ/g, respectively. Particularly, PCDFs among dioxin
      analogs generated remarkably at sites with a high TEQ. In addition, 79,000 t of
      ash was totally produced at five open-air incineration sites, and consequently
      the formation amount of PCDDs, PCDFs and Co-PCBs was estimated to be 70.7 gTEQ on
      the basis of these analytical data.

PMID- 11829400
TI  - The formation and emission of dioxins in large scale thermal processes.
AB  - The paper assesses extensive data of PCDD/F measurements on flue gas emissions
      from thermal processes, including, e.g. municipal solid waste incinerators
      (MSWIs), combustors of wood and industrial waste, coal fired powerplants and
      boilers, ferro and non-ferro processes. Numerous investigators have conducted
      laboratory experiments to assess the formation mechanisms of PCDD/F. The results,
      obtained from fixed-bed experiments, have been critically evaluated and indicate
      that de novo synthesis is the dominant mechanism in actual thermal processes
      where conditions that favour the precursor formation are not experienced. The
      analysis of PCDD/F profiles from the large scale thermal processes in general,
      and MSWIs in particular, supports the dominant role of the de novo synthesis,
      irrespective of the type of thermal process considered. The PCDF/PCDD ratio
      exceeds 1 and the degree of chlorination points towards the dominant presence of
      HpCDD and OCDD within the dioxin group, and of PeCDF, HxCDF and HpCDF within the
      furan group. Since real-time measurement of PCDD/F is impossible, the correlation
      of PCDD/F emissions with operating parameters and/or emission levels of other
      more easily measured pollutants could be a tool in predicting the PCDD/F
      formation levels. Data of Flemish MSWIs were used to statistically assess such
      correlations. From an evaluation of the data at a given operating temperature,
      misleading conclusions can be drawn. Only the effect of temperature is evident.
      After converting all data at a reference temperature of, e.g. 230 degrees C,
      PCDD/F concentrations achieve nearly constant values, irrespective of the values
      of other parameters, thus stressing that the major controlling parameter for the
      PCDD/F emission is the temperature of the ESP. The PCDD/F concentrations increase
      with temperature in the range up to 280 degrees C. The ESP temperature should be
      kept preferably between 180 degrees C and 200 degrees C, where de novo synthesis
      is reduced and where PCDD/Fs are increasingly adsorbed on the fly ash, in line
      with the standard temperature dependence of adsorption isotherms.

PMID- 11829401
TI  - Partitioning of polychlorinated biphenyls and hexachlorobenzene into human
      faeces.
AB  - The dietary absorption of persistent lipophilic organic pollutants (PLOPs) in
      humans is believed to occur via partitioning of the chemical between the lumen
      and the wall of the digestive tract. As such, the partitioning properties of the
      lumen contents are a key factor governing absorption. In this study, the
      partitioning properties of faeces were measured for 11 polychlorinated biphenyls
      and hexachlorobenzene (HCB). Four volunteers participated in the study, each of
      them providing faeces from a normal diet and a vegetarian diet. The faeces/gas
      equilibrium partition coefficient K(FG) varied by over three orders of magnitude
      between the different compounds. A linear relationship between log K(FG) and log
      KOA, the octanol/air partition coefficient, was observed. The slope of the
      relationship was > 1, indicating that the solvent properties of faeces were less
      polar than those of octanol. For a given compound, KFG varied up to a factor of
      2.8 between the individuals on a normal diet. The influence of the vegetarian
      diet on K(FG) was negligible for the two volunteers who simply deleted fish and
      animal products from their normal diet, but K(FG) increased on average by a
      factor of 2 in the two individuals who increased their consumption of less
      readily digestible whole grains and vegetables in their vegetarian diet. On the
      basis of K(FG), the fugacities in the faeces were calculated. They were found to
      be much lower than the fugacities in blood. It is hypothesised that this is due
      to a temporary decrease in the fugacity in the wall of the jejunum caused by
      absorption of dietary lipids that results in equilibration between the lumen
      contents and the wall of the digestive tract at a fugacity below that present in
      the blood and the rest of the body.

PMID- 11829402
TI  - PAHs composition of surface marine sediments: a comparison to potential local
      sources in Todos Santos Bay, B.C., Mexico.
AB  - The analysis of the 16 polyaromatic hydrocarbons (PAHs) listed as priority
      pollutants by EPA, was carried out on surface sediments at 32 stations at Todos
      Santos Bay, Baja California, Mexico. The purpose was to investigate concentration
      levels, distribution patterns and relate them to three suspected local sources.
      The PAHs composition of car exhaust, grass and shrubs combustion, and asphalt and
      tire dust, were all compared to the relative abundance of PAHs signature found on
      marine sediments of the bay. We used GC-MS analysis in selected ion monitoring
      (SIM) mode. The total concentration found was low (from 7.6 to 813 ng/g of dry
      sediment. The average concentration was 96 ng/g). PAHs concentration was somewhat
      correlated (r = 0.612; P < 0.05) with organic matter content. Surface
      distributions suggest depositional patterns conforming to the reported water
      circulation in the bay. The maximum concentration was found near Todos Santos
      Canyon. The largest concentrations found were those of fluoranthene (120.6 ng/g),
      Indene(1,2,3-c,d)pyrene (115.6 ng/g) and pyrene (109.9 ng/g). Percentagewise, the
      main components were PAHs with three and four rings. Several indexes were used to
      investigate origins including simple PAH ratios and ternary plots. These indexes
      and plots suggest the main origin as a combination of urban air and wood and
      brush fires with little influence of oil.

PMID- 11829403
TI  - Development of a simple selective SFE method for the determination of desorption
      behaviour of PCBs in two Swedish sediments.
AB  - A simple selective supercritical fluid extraction (SFE) method was developed for
      the determination of desorption behaviour of PCBs in sediments. This method was
      applied to determine the distribution of individual PCB congeners among sites of
      differing bonding strengths in two Swedish sediments (Lake Jarnsjon and Baltic
      bay Orserumsviken). Four different PCB fractions were distinguished in each
      sediment by applying consecutively harsher supercritical fluid extraction
      conditions on the same sample. Even though the two sediments had completely
      different textures, they showed very similar extraction behaviour. It was shown
      that, in both sediments, a major part of the PCBs (58% and 65%, respectively)
      were located at "fast sites", from which they were extractable already with the
      mildest extraction conditions (60 min, 40 degrees C and 120 bar). Only a small
      fraction of the PCBs were so tightly bound to the sediments (located at "slow
      sites"), that they could be extracted only under the harshest conditions (60 min,
      150 degrees C and 400 bar). Information of this kind should be of great value for
      the determination of bioavailability of pollutants in sediments and soils, and it
      is the author's belief that this technique has the potential to develop into a
      powerful tool in environmental risk assessment.

PMID- 11829404
TI  - PCB removal from contaminated dredged material.
AB  - The purpose of this study was to evaluate the feasibility of decontaminating PCB
      contaminated sediment using land treatment technology. Five glass aquariums were
      set up to test the disappearance of polychlorinated biphenyls (PCBs) in dredged
      sediment under laboratory conditions that simulated photodegradation, biological
      transformation, and volatilization in dredged material confined disposal
      facilities (CDFs). A 40% decline in PCB concentration was achieved over a period
      of 5 months. Analysis of the variance in the data showed that periodic tilling
      produced a tangible effect on the disappearance of PCBs. However, the process or
      processes responsible for PCB disappearance could not be determined. PCB
      disappearance from the sediment was most likely caused by a combination of
      photolysis, volatilization, and biodegradation mechanisms rather than by any
      single process.

PMID- 11829405
TI  - The three-dimensional structure of 3, 3', 5'-trichloro-4-methoxybiphenyl, a
      "coplanar" polychlorinated biphenyl (PCB) derivative.
AB  - The crystal structure of a "coplanar" polychlorinated biphenyl (PCB) derivative,
      4-methoxy-3, 3', 5'-trichlorobiphenyl (C13H9Cl3O), is described. The torsion
      angle of the title compound is 41.31(07) degrees, which is in good agreement with
      the calculated torsion angle of 38.2 degrees in aqueous solution.

PMID- 11829406
TI  - Is methamphetamine abuse a risk factor in parkinsonism?
AB  - Parkinsons disease (PD) is a neurodegenerative disorder with increased incidence
      in individuals beyond 50 years of age. The etiology of PD is currently not known,
      but it appears that environmental factors may play an important role. The
      molecular basis of PD is the nearly complete loss of the neurotransmitter
      dopamine (DA) in the basal ganglia (caudate/putamen). The decrease in dopamine
      levels is the result of degeneration of dopamine-containing neurons in the
      substantia nigra. This biochemical deficit in the nigrostriatal pathway leads to
      the emergence of motor impairments typical of PD. Methamphetamine (METH) is a
      psychostimulant drug with increasing use in certain segments of the population in
      the United States and worldwide. In experimental animal models and human studies,
      METH administration has been shown to decrease markers of dopaminergic neuron
      terminal integrity in the basal ganglia. A long-standing question has been
      whether the reductions in dopaminergic markers induced by METH constitute
      degenerative changes or reflect drug-induced modulation. Resolving this question
      is important because the irreversible loss of dopaminergic function may increase
      the likelihood of Parkinsonism with advancing age.

PMID- 11829407
TI  - Morphological study of 5-HT neurons and astroglial cells on brain of adult rats
      perinatal or chronically exposed to 2,4-dichlorophenoxyacetic acid.
AB  - 2,4-D is a chlorophenoxyherbicide used worldwide. We have studied the
      morphological alterations of 5-HT neurons and glial cells in the mesencephalic
      nuclei of adult rats exposed to 2,4-D both perinatally (during pregnancy and
      lactation) and chronically (during pregnancy, lactation and after weaning) with
      quantitative methods. Pregnant rats were daily exposed to 70 mg/kg of 2,4-D from
      gestation day (GD) 16 to post-natal day (PND) 23 through diet. After weaning,
      pups were assigned to one of two sub-groups: T1 (fed with untreated diet until
      PND 90) and T2 (maintained with 2,4-D diet until PND 90). Brain sections were
      immunocytochemically stained using polyclonal anti-5-HT, anti-GFAP and anti-S-100
      protein antibodies as cells markers. 2,4-D exposure during pregnancy and lactancy
      (T1 group) produced an increase in 5-HT neuronal area and immunoreactivity (IR)
      in the mesencephalic nuclei studied. However, with the chronical 2,4-D exposure
      (T2 group) only the 5-HT neuronal area from the dorsal raphe nucleus (DRN) was
      increased, suggesting an adaptable response of 5-HT neurons in median raphe
      nucleus (MRN). The presence of reactive astrocytes in mesencephalic nuclei and in
      hippocampus were also different for the two 2,4-D exposure designs, showing the
      existence of a correspondence between neuronal changes and astrogliosis. Results
      support evidences that 2,4-D alters the serotoninergic system and that 5-HT
      neurons of each mesencephalic nuclei show different responses to the 2,4-D
      exposure designs which are parallel to astrogliosis.

PMID- 11829408
TI  - Modulation of tetrodotoxin-resistant sodium channels by dihydropyrazole
      insecticide RH-3421 in rat dorsal root ganglion neurons.
AB  - The effects of the dihydropyrazole insecticide RH-3421 on the retrodotoxin
      resistant (TTX-R) voltage-gated sodium channels in rat dorsal root ganglion (DRG)
      neurons were studied using the whole-cell patch clamp technique. RH-3421 at 10 nM
      to 1 microM completely blocked action potentials. The sodium currents were
      irreversibly suppressed by 1 microM RH-3421 in a time- and a dose-dependent
      manner and the IC50 value of RH-3421 was estimated to be 0.7 microM after 10 min
      of application. RH-3421 blocked the sodium currents to the same extent over the
      entire range of test potentials. The sodium conductance-voltage curve was not
      shifted along the voltage axis by 1 microM RH-3421 application In contrast, both
      fast and slow steady-state sodium channel inactivation curves were shifted in the
      hyperpolarizing direction in the presence of 1 microM RH-3421. It was concluded
      that RH-3421 bound to the resting and inactivated sodium channels to cause block
      with a higher affinity for the latter state.

PMID- 11829409
TI  - Point mutations in homology domain II modify the sensitivity of rat Nav1.8 sodium
      channels to the pyrethroid insecticide cismethrin.
AB  - Two point mutations in homology domain II of the housefly Vsscl voltage-sensitive
      sodium channel subunit, M918T and L1014F are associated with resistance to
      pyrethroid insecticides and reduce the pyrethroid sensitivity of Vsscl sodium
      channels expressed in Xenopus laevis oocytes. To assess the impact of these
      residues as determinants of pyrethroid sensitivity in another sequence context,
      we mutated the corresponding positions of the rat pyrethroid-sensitive, TTX
      resistant peripheral nerve sodium channel (rNav1.8; also called SNS or PN3) and
      determined the sensitivity of native and mutated channels expressed in Xenopus
      oocytes to the pyrethroid insecticide cismethrin. The rNav1.8 channel, like other
      vertebrate sodium channel isoforms, contains a conserved isoleucine residue at
      sequence position 780 that aligns with the conserved methionine at position 918
      of Vsscl and other insect sodium channels. Channels mutated to contain methionine
      at position 780 (1780M) exhibited enhanced sensitivity to cismethrin and larger
      decay constants for pyrethroid-modified channel states. In contrast, the mutation
      corresponding to M918Tin the Vssc1 channel (1780T) profoundly decreased the
      cismethrin sensitivity of expressed channels. Insertion of the mutation
      corresponding to L1014F (L879F in rNav1.8) reduced the cismethrin sensitivity of
      channels having either isoleucine or methionine at position 780, whereas channels
      containing the 1780T/L879F double mutation were insensitive to this insecticide.
      Mutations at Ile780 and Leu879 also modified the voltage dependence of rNav1.8
      channels, but these effects were not related to changes in pyrethroid
      sensitivity. These results confirm the importance of residues in homology domain
      II as fundamental determinants of the pyrethroid sensitivity of sodium channels.

PMID- 11829410
TI  - Inhibition of catalase activity with 3-amino-triazole enhances the cytotoxicity
      of the Alzheimer's amyloid-beta peptide.
AB  - Amyloid-beta, (Abeta) is a cytotoxic peptide implicated in the pathology of
      Alzheimers disease. The antioxidant enzyme catalase has been suggested to protect
      against Abeta cytotoxicity in both neuronal and non-neuronal cell types.
      Inhibition of endogenous catalase using 3-amino-1,2,4-triazole (3AT) in neuronal
      (NT-2) and myeloma (SP2/0-Ag-14) cell lines increases Abeta toxicity, suggesting
      that any protective role for endogenous catalase requires active enzyme. In Abeta
      treated mveloma cells there was a significant decrease in the total cell catalase
      activity and immunoreactivity. However, when the surviving live cell population
      was isolated following Abeta treatment the levels of catalase were significantly
      increased. The surviving live cell population from groups treated with both 3AT
      and Abeta contain elevated immunoreactive catalase levels suggesting that the
      protective role for endogenous catalase may have a component independent of the
      antioxidant activity, possibly by acting as an Abeta binding protein. Amyloid
      beta (Abeta) cytotoxicity can be prevented by Vitamin E treatment or an anti
      Abeta monoclonal antibody (ALIOI), both of which also prevent Abeta cytotoxicity
      in cells treated with 3AT These observations suggest that Abeta mediated cell
      death in both neuronal and non-neuronal cells is mediated in part by actions to
      increase hydrogen peroxide. Catalase has a protective role, as a hydrogen
      peroxide-degrading enzyme and catalase inhibition by Abeta is not the direct
      cause of cytotoxicity.

PMID- 11829411
TI  - Neuromuscular transmission and muscle contractility in SNAP-25-deficient coloboma
      mice.
AB  - Synaptosomal associated protein of 25 kDa (SNAP-25) is a cytoplasmic protein that
      participates in the docking and fusion of synaptic vesicles with the nerve
      terminal in preparation for neurotransmitter release. SNAP-25 is also a substrate
      for three of the seven serotypes of botulinum neurotoxin (BoNT). Intoxication by
      BoNT/A, /C1 or /E results in weakness and paralysis of skeletal muscle due to
      cleavage of SNAP-25 (and syntaxin la in the case /C1) at discrete serotype
      specific sites. To elucidate the role of SNAP-25 in muscle function in more
      detail, contractility and neuromuscular transmission were studied in a mutant
      mouse model termed coloboma. The coloboma mutation results from a contiguous
      deletion of 1-2 centiMorgans on chromosome 2, which includes the entire SNAP-25
      locus and three other identified genes. Homozygotes do not survive beyond
      gestation day 6; heterozygotes (Cm/+) have a normal life-span but express reduced
      levels of SNAP-25 mRNA and protein in the brain. The consequences of the Cm/+
      mutation on twitch and tetanic tension, quantal release of neurotransmitter and
      spinal motoneuron expression of SNAP-25 were examined in the present study.
      Contrary to expectations, Cm/+ mice exhibited no alteration in twitch tension and
      generated normal tetanic tension even at the highest frequency examined (800 Hz).
      Microelectrode recordings revealed that MEPP amplitude and frequency were both
      within control limits. The ventral spinal cord of Cm/+ mice showed no deficiency
      in SNAP-25 content and immunohistochemical examination of nerve terminals in Cm/+
      mice disclosed that SNAP-25 levels and distribution were similar to those of
      control mice. It is concluded that spinal motor neurons up-regulate SNAP-25 to
      preserve vital neuromuscular function.

PMID- 11829412
TI  - The effect of continuous pyridostigmine administration on functional (A12)
      acetylcholinesterase activity in guinea-pig muscles.
AB  - Pyridostigmine which causes a reversible inhibition of acetylcholinesterase
      (AChE), was administered continuously for 6 days to guinea-pigs, via a
      subcutaneously implanted osmotic pump. This produced 40-50% inhibition of red
      cell acetylcholinesterase (AChE). Controls were animals treated with saline via
      pumps, and untreated animals. The activities of the functional A12 molecular form
      of AChE were compared in diaphragm, extensor digitorum longus (EDL) and soleus
      muscles in the three animal groups at 6 days. The pumps were removed at 6 days
      and the A12 AChE activities were determined at various times thereafter As the
      enzyme separation procedure was lengthy, drug-induced inhibition was no longer
      present when the enzyme activity was measured. At 6 days, the activity was
      significantly higher in EDL (over 50% higher) and soleus (over two-fold higher)
      in pyridostigmine-treated animals than saline-treated animals. In the diaphragm,
      the activities in pyridostigmine and saline-treated animals were similar but both
      were significantly (over two-fold) higher than in untreated animals. At 1 day
      after pump removal (day 7) the activity had declined in all three muscles of the
      pyridostigmine-treated animals and in the diaphragm of saline-treated animals.
      Thereafter, in the diaphragm (but not the EDL or soleus) in pyridostigmine
      treated animals, there were marked variations in the enzyme activity up to day
      20. In saline-treated animals there was a marked transient increase in activity
      at day 13 in all muscles. The results indicate that the homeostatic control
      offunctional AChE had been affected in both the pyridostigmine and saline
      treatment groups.

PMID- 11829413
TI  - Neurogenic inflammation and particulate matter (PM) air pollutants.
AB  - Exposure to a class of airborne pollutants known as particulate matter (PM) is an
      environmental health risk of global proportions. PM is thought to initiate and/or
      exacerbate respiratory disorders, such as asthma and airway hyper-responsiveness
      and is epidemiologically associated with causing death in the elderly and those
      with pre-existing respiratory, or cardiopulmonary disease. Plausible mechanisms
      of action to explain PM inflammation and its susceptible sub-population component
      are lacking. This review describes a series of published studies which indicate
      that PM initiates airway inflammation through sensory neural pathways,
      specifically by activation of capsaicin-sensitive vanilloid (e.g. VRI) irritant
      receptors. These acid-sensitive receptors are located on the sensory C nerve
      fibers that innervate the airways as well as on various immune and non-immune
      airway target cells. The activation of these receptors results in the release of
      neuropeptides from the sensory terminals that innervate the airways. Their
      interactions with airway target cells, result in signs of inflammation (e.g.
      bronchoconstriction, vasodilation, histamine release, mucous secretion etc.). Our
      data have linked the activation of the VR1 receptors to the surface charge
      carried on the colloidal particulates which constitute PM pollution. Related
      studies have examined how genetic and non-genetic factors modify the sensitivity
      of these irritant receptors and enhance the inflammatory responsiveness to PM. In
      summary, this review proposes a mechanism by which neurogenic elements initiate
      and sustain PM-mediated airway inflammation. Although neurogenic influences have
      been appreciated in normal airway homeostasis, they have not, until now, been
      associated with PM toxicity. The sensitivity of the sensory nervous system to
      irritants and its interactions with pulmonary target tissues, should encourage
      neuroscientists to explore the relevance of neurogenic influences to toxic
      disorders involving other peripheral target systems.

PMID- 11829414
TI  - Striatal dopaminergic pathways as a target for the insecticides permethrin and
      chlorpyrifos.
AB  - Because insecticide exposure has been linked to both Parkinsons disease and Gulf
      War illness, the neurotoxic actions of pyrethroid and organophosphate
      insecticides on behavior and striatal dopaminergic pathways were investigated in
      C57BL/6 mice treated with permethrin (three i.p. doses at 0.2-200 mg/kg) or
      chlorpyrifos (three s.c. doses at 25-100 mg/kg) over a 2-week period. Permethrin
      altered maximal [3H]dopamine uptake in striatal synaptosomes from treated mice,
      with changes in Vmax displaying a bell-shaped curve. Uptake was increased to 134%
      of control at a dose of 1.5 mg/kg. At higher doses of PM (25 mg/kg), dopamine
      uptake declined to a level significantly below that of control (50% of control at
      200 mg/kg, P < 0.01). We also observed a small, but statistically significant
      decrease in [3H]dopamine uptake by chlorpyrifos, when given at a dose of 100
      mg/kg. There was no significant effect on the Km for dopamine transport. Evidence
      of cell stress was observed in measures of mitochondrialfunction, which were
      reduced in mice given high-end doses of chlorpyrifos and permethrin. Although
      cytotoxicity was not reflected in decreased levels of striatal dopamine in either
      200 mg/kg PM or 100 mg/kg CPF treatment groups, an increase in dopamine turnover
      at 100 mg/kg CPF was indicated by a significant increase in titers of the
      dopamine metabolite, 3,4-dihydroxyphenylacetic acid. Both permethrin and
      chlorpyrifos caused a decrease in open field behavior at the highest doses
      tested. Although frank Parkinsonism was not observed, these findings confirm that
      dopaminergic neurotransmission is affected by exposure to pyrethroid and
      organophosphorus insecticides, and may contribute to the overall spectrum of
      neurotoxicity caused by these compounds.

PMID- 11829415
TI  - Organophosphorus compounds alter intracellular F-actin content in SH-SY5Y human
      neuroblastoma cells.
AB  - Cytoskeletal components, especially f-actin (filamentous actin), are responsible
      for neurite extension and maintenance. Alterations in neurite length and quality
      precede in vitro cell death induced by organophosphorus (OP) compounds and
      implicate f-actin proteins in this process. We, therefore, investigated changes
      in f-actin in SH-SY5Y human neuroblastoma cells exposed to 0.1 and 1 mM paraoxon,
      parathion, phenyl saligenin phosphate (PSP), tri-ortho-tolyl phosphate (TOTP),
      triphenyl phosphite (TPPi), and di-isopropyl phosphorofluoridate (DFP) for 0-48
      h. The f-actin was measured by flow cytometry in cells labeled with Alexa 488
      phalloidin. The relative amount off-actin was compared to total protein levels as
      determined by spectrophotometry. The cellular content of f-actin significantly
      decreasedfollowing exposure to PSP (0.1 mM, >30 min; 1 mM, >15 min), TOTP (0.1
      mM, 16 h; 1 mM, >15 min), TPPi (1 mM, >4 h), paraoxon (1 mM, >24 h), and
      parathion (1 mM, 48 h). Exposure to DFP (0.1 and 1 mM) did not significantly
      alter f-actin content at any time point. Exposure to parathion (0.1 mM, 48 h)
      significantly increased the amount of cellular f-actin. Total protein was
      significantly decreased after exposure to PSP (0.1 and 1 mM, >8 h) and TPPi (1
      mM, 48 h). Significant increases in total protein were observed following
      exposure to parathion (0.1 mM, >3 h). Consistent alterations in the protein
      content of DFP-exposed samples were not observed. These results suggest that the
      loss off-actin is an early event following OP compound exposure and that this
      loss significantly precedes a loss of protein content for some OP compounds (PSP,
      TPPi). Results also imply that under other exposure conditions (TOTP, paraoxon,
      parathion) alterations in the f-actin content are independent of protein content.

PMID- 11829416
TI  - Parkinson's disease, environment and genes.

PMID- 11829417
TI  - Clinical and neuropathological features: session III summary and research needs.

PMID- 11829418
TI  - Epidemiological studies: risk factors session IV summary and research needs.

PMID- 11829419
TI  - Genetic risk factors: session V summary and research needs.

PMID- 11829420
TI  - Selected presentations and general discussion: session IX summary and research
      needs.

PMID- 11829421
TI  - Mechanisms of parkinsonism: session X summary and research needs.

PMID- 11829422
TI  - Therapeutic approaches: session XI summary and research needs.

PMID- 11829423
TI  - "Necessary" transfusions and prognosis in gastric cancer.

PMID- 11829424
TI  - Indications and use of palliative surgery-results of Society of Surgical Oncology
      survey.
AB  - BACKGROUND: Despite increasing attention to end-of-life care in oncology,
      palliative surgery (PS) remains poorly defined. A survey to test the definition,
      assess the extent of use, and evaluate attitudes and goals of surgeons regarding
      PS was devised. METHODS: A survey of Society of Surgical Oncology (SSO) members.
      RESULTS: 419 SSO members completed a 110-item survey. Surgeons estimated 21% of
      their cancer surgeries as palliative in nature. Forty-three percent of
      respondents felt PS was best defined based on pre-operative intent, 27% based on
      post-operative factors, and 30% on patient prognosis. Only 43% considered
      estimated patient survival time an important factor in defining PS, and 22%
      considered 5-year survival rate important. The vast majority (95%) considered
      tumor still evident following surgery in a patient with poor prognosis
      constituted PS. Most surgeons felt PS could be procedures due to generalized
      illness related to cancer (80%) or related to cancer treatment complications
      (76%). Patient symptom relief and pain relief were identified as the two most
      important goals in PS, with increased survival the least important. CONCLUSION:
      PS is a major portion of surgical oncology practice. Quality-of-life parameters,
      not patient survival, were identified as the most important goals of PS.

PMID- 11829425
TI  - Occurrence and prognostic implications of micrometastases in lymph nodes from
      patients with submucosal gastric carcinoma.
AB  - BACKGROUND: The aims of this study were to assess the incidence of
      micrometastases of lymph nodes in patients with early gastric cancer invading the
      submucosal layer and to investigate the correlation between nodal micrometastases
      and malignancy potential to determine whether micrometastases of lymph nodes have
      prognostic significance, by use of an anticytokeratin immunohistochemical
      technique. METHODS: A total of 2272 lymph nodes taken from 88 patients (25.8 per
      case) were assessed by immunohistochemical technique by use of monoclonal anti
      human cytokeratin 8 antibodies. Clinicopathologic parameters and prognosis were
      compared between patients with and without micrometastases. RESULTS: The
      incidence of nodal involvement by tumor cells in 88 patients with submucosal
      gastric cancer increased from 19.3% (17 patients) by hematoxylin-eosin (H&E)
      staining to 31.8% (28 patients) by cytokeratin immunostaining. The rate of
      positive node in this study increased from 1.0% (23 of 2272 nodes) by H&E
      staining to 2.5% (57 of 2272 nodes) by immunostaining (P = .0002). No correlation
      was observed between the incidence of lymph node micrometastases and various
      clinicopathologic parameters, including tumor site and size, histological
      differentiation, Lauren classification, gross tumor type, vascular and lymphatic
      invasion, and perineural invasion. There was no difference in disease-free
      survival, estimated by the Kaplan-Meier life-table method, between the
      micrometastasis-negative and -positive groups (95% and 92.9%, respectively).
      Multivariate analyses showed that tumor size and diffuse subtype by the Lauren
      classification were significant factors for survival time (P = .0042 and .014,
      respectively). CONCLUSIONS: Immunohistochemical staining with an anticytokeratin
      antibody seems to be of little prognostic value in patients with submucosal
      gastric carcinoma. Thus, this immunostaining technique does not offer a
      significant benefit of different strategies for additional therapy or follow-up
      over conventional pathologic staging with H&E staining.

PMID- 11829426
TI  - Tumor angiogenesis in lymph node-negative rectal cancer: correlation with
      clinicopathological parameters and prognosis.
AB  - BACKGROUND: Intratumoral microvessel density (MVD) could be used as a prognostic
      factor in colorectal cancer. We retrospectively analyzed the value of microvessel
      count in predicting the clinical outcome of stage I and II (Dukes A and B) rectal
      cancer patients. METHODS: Eighty-four patients who had undergone curative
      resection of lymph node-negative rectal cancer were included. Tumor type and
      differentiation, the depth of local invasion, venous invasion, the character of
      the invasive margin, and the degree of lymphocytic infiltration were evaluated
      for each tumor specimen. Immunohistochemical staining for the CD31 endothelial
      antigen was performed to highlight the microvessels. RESULTS: The median value of
      MVD was 45 microvessels. Low MVD (microvessels < or = 45) was observed in 41
      patients (48.8%), and high MVD (>45) was found in 43 (51.2%). The presence of
      conspicuous lymphocytic infiltration was significantly associated with increased
      vessel density. With uni- and multivariate survival analysis MVD did not show any
      prognostic significance. The character of the invasive margin was the only
      parameter with independent prognostic value. CONCLUSIONS: MVD does not seem to
      provide any additional prognostic information when compared with standard
      histopathological parameters in lymph node-negative rectal cancer. It is likely
      that the strong association between MVD and the presence of conspicuous
      lymphocytic infiltration may interfere with its predictive value.

PMID- 11829427
TI  - The superiority of ratio-based lymph node staging in gastric carcinoma.
AB  - BACKGROUND: The need for a precise lymph node staging without stage migration is
      of paramount importance when comparing and evaluating international treatment
      results. METHODS: We reviewed 1019 patients who underwent R0 resection at Kansai
      Medical University between 1980 and 1997. The patients were classified according
      to the 1997 International Union Against Cancer (UICC)/American Joint Committee on
      Cancer (AJCC) pN classification or the N staging depending on the ratio between
      the number of excised and the number of involved lymph nodes (pN1, < or = 25%;
      pN2, < or = 50%; pN3, >50%). RESULTS: Among the 1997 UICC/AJCC pN subgroups,
      prognosis worsened with an increase in lymph node ratio. In contrast, the ratio
      based classification showed more homogenous survival according to the number of
      involved lymph nodes. Multiple stepwise regression analysis showed that the ratio
      based classification was the most significant prognostic factor, whereas the 1997
      UICC/AJCC classification was not found to be an independent predictor of
      survival. In addition, the ratio-based classification showed a superiority to the
      1997 UICC/AJCC classification with respect to stage migration. CONCLUSIONS: Ratio
      based lymph node staging is simple and gives more precise information for
      prognosis with fewer problems related to stage migration than the 1997 UICC/AJCC
      staging system.

PMID- 11829428
TI  - Solid-pseudopapillary tumor of the pancreas: challenges presented by an unusual
      pancreatic neoplasm.

PMID- 11829429
TI  - Resection of the sciatic, peroneal, or tibial nerves: assessment of functional
      status.
AB  - BACKGROUND: Lower-extremity tumors are often treated by amputation rather than
      limb-sparing excision that sacrifices the sciatic nerve or a branch. This study
      assessed the functional outcome of major nerve sacrifice during limb-sparing
      resections for lower-extremity soft tissue sarcoma. METHODS: Patients who
      underwent division of the sciatic, tibial, or peroneal nerve(s) during limb
      sparing sarcoma surgery (January 1982 through June 2000) were identified. Eleven
      surviving patients evaluated their pre- and postoperative functional status by
      self-administered questionnaire (six sciatic, two tibial, and three peroneal
      nerve divisions). RESULTS: Eighteen patients (10 male, 8 female; 14-84 years old)
      had nine primary and nine locally recurrent tumors. Tumors were high (16) or low
      grade (two). Five patients died of disease and two died of other causes. Median
      overall survival was 50 months. One of 11 reported increased pain. Eight had new
      phantom sensations with a median intensity of 4.5 (1 = least; 10 = most). All
      patients used an ankle brace to walk after a sciatic (four) or peroneal (one)
      division. Walking ability and distance after surgery was unchanged (nine),
      improved (one), and worsened (one). Standing improved in 7 of 11 patients.
      Proprioception in the affected extremity was retained in six. The median
      postoperative leg functional score was 8 (1 = worst; 10 = best). No patient
      developed foot ulcers. One patient underwent amputation for recurrence. All
      patients preferred their status over having an amputation. CONCLUSIONS:
      Objectively and subjectively, division of the major lower-extremity nerves causes
      acceptable functional deficits in most patients. Resection of affected sciatic
      nerve (branches) during limb-sparing tumor surgery is an excellent alternative to
      amputation.

PMID- 11829430
TI  - Adjuvant brachytherapy for primary high-grade soft tissue sarcoma of the
      extremity.
AB  - BACKGROUND: We reviewed single-institution experience using brachytherapy alone
      for primary high-grade soft tissue sarcoma of the extremity. METHODS: Between
      July 1982 and September 1997, 202 adult patients with primary high-grade soft
      tissue sarcoma of the extremity were treated with limb-sparing surgery and
      adjuvant brachytherapy. All patients underwent complete gross resection, but the
      margin of resection was microscopically positive in 18% of patients. The median
      dose of brachytherapy was 45 Gy delivered over 5 days. Tumors located in the
      shoulder or groin were defined as central location. Complications were assessed
      in terms of wound complications, bone fracture, and peripheral nerve damage.
      RESULTS: With a median follow-up of 61 months, the 5-year local control, distant
      relapse-free survival, and overall survival rates were 84%, 63%, and 70%,
      respectively. On multivariate analysis, poor local control correlated with
      shoulder location, positive microscopic margins of resection, and nonshoulder
      upper extremity site. The 5-year actuarial rates of wound complications requiring
      reoperation, bone fracture, and grade > or = 3 nerve damage were 12%, 3%, and 5%,
      respectively. CONCLUSIONS: Adjuvant brachytherapy provides adequate local control
      and acceptable morbidity that compares favorably with data reported for external
      beam radiation. Shoulder tumor location was identified as an independent
      prognostic factor for poor local control, mandating further improvement in the
      local management of these tumors.

PMID- 11829431
TI  - Adverse effects of perioperative transfusion on patients with stage III and IV
      gastric cancer.
AB  - BACKGROUND: The degree of immunomodulation by perioperative blood transfusion and
      its resultant effects on cancer surgery are a subject of controversy. We
      evaluated the prognostic effects of perioperative blood transfusion on gastric
      cancer surgery. METHODS: A total of 1710 patients who underwent curative
      gastrectomy for gastric cancer from 1991 to 1995 were retrospectively reviewed.
      Uni- and multivariate analyses of the incidence, amount, and timing of
      perioperative blood transfusions and a comparison of the clinicopathological
      features were performed. RESULTS: A higher incidence of blood transfusions was
      associated with female sex, large tumors, upper-body location, Borrmann type III
      or IV lesions, longer operations, total gastrectomies, splenectomies, and D3 or
      more extended lymphadenectomy. The tumors in the transfused group were more
      advanced in depth of invasion and nodal classification. More frequent tumor
      recurrences were found in the transfused group. A dose-response relationship
      between the amount of transfused blood and prognosis was evident. Subgroup
      analyses of prognosis according to stage showed significant differences in stages
      III and IV between the transfused and nontransfused groups. On multivariate
      analysis, transfusion was shown to be an independent risk factor for recurrence
      and poor prognosis. CONCLUSIONS: These results suggest that perioperative
      transfusion is an unfavorable prognostic factor. It is thus better to refrain
      from unnecessary blood transfusion and to give the least amount of blood to
      patients with gastric cancer when transfusion is inevitable, especially for those
      with stage III and IV gastric cancers.

PMID- 11829432
TI  - Paratracheal lymph node metastasis is associated with cervical lymph node
      metastasis in patients with thoracic esophageal squamous cell carcinoma.
AB  - BACKGROUND: We determined which lymph node metastases were associated with
      cervical lymph node metastases of thoracic esophageal squamous cell carcinoma.
      METHODS: A total of 6464 lymph nodes derived from 155 consecutive patients with
      thoracic esophageal squamous cell carcinoma were stained by immunohistochemistry
      (antibody: AE1/AE3). Lymph node metastases were mapped according to the mapping
      scheme of the American Thoracic Society, as modified by Casson et al. (Ann Thorac
      Surg 1994;58:1569-70). Patients were divided into two groups: those with and
      without cervical lymph node metastasis (CLNM). Mapping data were examined by uni-
      and multivariate analysis. RESULTS: Hematoxylin and eosin-positive and AE1/AE3
      positive lymph node metastases were found in 59% and 77% of patients,
      respectively. Twenty-one (55%) of 38 patients in the CLNM(+) group and 30 (26%)
      of 117 patients in the CLNM(-) group had AE1/AE3-positive lymph node metastasis
      in the thoracic paratracheal lymph node. Paratracheal lymph node metastasis is
      only one independent factor for (CLNM), whereas upper thoracic paraesophageal
      lymph node and pulmonal hilar lymph node status were also significant in
      univariate analysis. Three (43%) of seven patients with cervical jumping
      metastasis from the thoracic esophagus had micrometastasis in the paratracheal
      lymph node. CONCLUSIONS: The paratracheal lymph node is most associated with
      (CLNM) of thoracic esophageal squamous cell carcinoma.

PMID- 11829433
TI  - Persistence of tumor DNA in plasma of breast cancer patients after mastectomy.
AB  - BACKGROUND: We investigated tumor DNA changes before and after mastectomy in the
      plasma of breast cancer patients with no disseminated disease and eventually
      investigated these changes' relationship to specific pathological parameters of
      the tumors. METHODS: We studied 41 patients. DNA extracted from tumor and normal
      breast tissues, mononuclear blood cells, and plasma was used for molecular
      studies. Alterations in the microsatellite markers D17S855, D17S654, D16S421,
      TH2, D10S197, and D9S161, as well as point mutations in the p53 gene and aberrant
      methylation of p16(INK4a), were used to identify and characterize tumor and
      plasma DNA. A number of tumor clinicopathological parameters were analyzed in
      each patient. RESULTS: We found that 18 (44%) of the 27 patients with alterations
      in tumor DNA presented the same plasma DNA alteration before mastectomy, and
      persistence of the same molecular features was detected in plasma DNA 4 to 6
      weeks postmastectomy in 8 (19.5%) patients. Patients with vascular invasion, more
      than three lymph node metastases, and higher histological grade at diagnosis
      displayed plasma DNA after mastectomy with a significant difference. CONCLUSIONS:
      Persistence of plasma DNA with features of tumor DNA may be present after
      mastectomy in breast cancer patients, and its relation to bad-prognosis
      histological parameters may suggest undetectable micrometastatic disease.

PMID- 11829434
TI  - Subareolar injection of 99mTc facilitates sentinel lymph node identification.
AB  - BACKGROUND: Sentinel lymph node (SLN) biopsy with the standard intraparenchymal
      injection has been accepted as an alternative to routine axillary dissection for
      patients with breast cancer. However, the identification and false-negative rates
      with this method can vary widely from surgeon to surgeon. The subareolar location
      contains a rich lymphatic network and represents a potential site of injection
      for SLN identification. METHODS: Between August 1, 1999, and December 31, 2000,
      we performed 159 SLN biopsy procedures on 158 patients with breast cancer. For
      each patient, 99mTc-labeled sulfur colloid was injected into the subareolar
      location, and 1% isosulfan blue dye was given as an intraparenchymal injection.
      RESULTS: In every case, at least one radioactive SLN was identified with the
      subareolar injection of technetium; a blue SLN was found in 97% of the cases. The
      blue SLN was also radioactive in 98% of the cases, indicating that the blue dye
      injected around the tumor and the technetium injected into the subareolar
      location drained to the same SLN. CONCLUSIONS: Subareolar injection of technetium
      can improve SLN identification rates for breast cancer. The simplicity and
      accuracy of this technique may also reduce the variable results reported with the
      standard intraparenchymal method.

PMID- 11829435
TI  - Sentinel node mapping identifies vaccine-draining lymph nodes with tumor-specific
      immunological activity.
AB  - BACKGROUND: Adoptive immunotherapy (AIT) with 4T07-IL2 vaccine-draining lymph
      node (DLN) cells induced regression of established 4T07 mammary carcinomas, but
      contralateral non-DLN were inactive. These experiments were performed to
      determine whether mapping with isosulfan blue (IB), as described for
      identification of sentinel nodes, would identify vaccine-DLN with antitumor
      activity. METHODS: Ten days after vaccination with 4T07-IL-2, .1 ml of 1% IB was
      injected into the vaccination site (footpads or flanks). After 3 minutes, mice
      were euthanized, and the blue-stained nodes were collected. With flank
      vaccination, IB identified both an inguinal and an axillary node. We also
      collected DLNs blindly in mice not receiving IB dye. DLN cell suspensions were
      then activated with bryostatin 1, ionomycin, and IL-2, expanded in culture, and
      adoptively transferred to mice bearing established 4T07 flank tumors. RESULTS:
      Complete tumor regression occurred in nearly all mice treated with popliteal or
      inguinal DLNs collected with or without IB. IB-stained axillary DLNs cured 100%
      of tumor-bearing mice, whereas none of the mice treated with blindly collected
      axillary DLNs were cured. CONCLUSION: We have shown that IB identifies
      immunologically active DLNs, does not interfere with expansion of lymphocytes in
      vitro, and, more importantly, has no detrimental effect on the ability of
      lymphocytes to induce tumor regression in vivo. For axillary DLNs, use of IB
      mapping identified immunologically active lymph nodes that could not otherwise be
      found.

PMID- 11829436
TI  - Release of triamcinolone acetonide from mucoadhesive polymer composed of chitosan
      and poly(acrylic acid) in vitro.
AB  - Transmucosal drug delivery (TMD) system using mucoadhesive polymer has been
      recently interested due to the rapid onset of action, high blood level, avoidance
      of the first-pass effect and the exposure of the drug to the gastrointestinal
      tract. A novel mucoadhesive polymer complex composed of chitosan and poly(acrylic
      acid) (PAA) was prepared by template polymerization of acrylic acid in the
      presence of chitosan for the TMD system. Triamcinolone acetonide (TAA) was loaded
      into the chitosan/PAA polymer complex film. TAA was evenly dispersed in chitosan,
      PAA polymer complex film without interaction with polymer complex. Release
      behavior of TAA from the mucoadhesive polymer film was dependent on time, pH,
      loading content of drug, and chitosan PAA ratio. The analysis of the drug release
      from the mucoadhesive film showed that TAA might be released from the
      chitosan/PAA polymer complex film through non-Fickian diffusion mechanism.

PMID- 11829437
TI  - In vitro and in vivo antimicrobial activity of covalently coupled quaternary
      ammonium silane coatings on silicone rubber.
AB  - Biomaterial-centered infection is a dreaded complication associated with the use
      of biomedical implants. In this paper, the antimicrobial activity of silicone
      rubber with a covalently coupled 3-(trimethoxysilyl)
      propyldimethyloctadecylammonium chloride (QAS) coating was studied in vitro and
      in vivo. Gram-positive Staphylococcus aureus ATCC 12600, Staphylococcus
      epidermidis HBH, 102, and Gram-negative Esherichia coli O2K2 and Pseudomonas
      aeruginos AK1 were seeded on silicone rubber with and without QAS-coating, in the
      absence or presence of adsorbed human plasma proteins. The viability of the
      adherent bacteria was determined using a live/dead fluorescent stain and a
      confocal laser scanning microscope. The coating reduced the viability of adherent
      staphylococci from 90% to 0%), and of Gram-negative bacteria from 90% to 25%
      while the presencc of adsorbed plasma proteins had little influence. The
      biomaterials were also subcutaneously implanted in rats for 3 or 7 days, while
      pre- or postoperatively seeded with S. aureus ATCC 12600. Preoperative seeding
      resulted in infection of 7 out of 8 silicone rubber implants against 1 out of 8
      QAS-coated silicone rubber implants. Postoperative seeding resulted in similar
      infection incidences on both implant types, but the numbers of adhering bacteria
      were 70% lower on QAS-coated silicone rubber. In conclusion, QAS-coated silicone
      rubber shows antimicrobial properties against adhering bacteria, both in vitro
      and in vivo.

PMID- 11829439
TI  - Effects of the sterilisation method on the wear of UHMWPE acetabular cups tested
      in a hip joint simulator.
AB  - Ultra-high molecular-weight-polyethylene is the most commonly used bearing
      material in total joint replacement. Wear of polyethylene is a Serious Clinical
      problem that limits the longevity of orthopaedic implants. Information on
      degradative changes in the material properties and on the methods used for the
      sterilisation of polyethylene may help in the selection process of orthopaedic
      implants with the best wear resistance. This study was performed to investigate
      the effects of the sterilisation method (gamma irradiation and ethylene oxide
      treatment) on the wear and on the changes in physical properties of polyethylene
      acetabular cups. At this purpose, gamma-sterilised and ethylene oxide (EtO)
      sterilised acetabular cups were tested against CoCr femoral heads in a hip joint
      simulator run for 5 million cycles in bovine calf serum. The crystallinity of the
      cups was evaluated by micro-Raman spectroscopy as a function of the inner surface
      position. The partial least square calibration was used to correlate the Raman
      spectra with the crystallinity of the polymer measured by differential scanning
      calorimetry. The analysis performed on soak control acetabular cups demonstrated
      that the gamma-sterilised cups are significantly more crystalline than the EtO
      sterilised ones. The mean crystallinity values obtained for the gamma-sterilised
      and EtO-sterilised soak control cups were 65.0% and 63.4%, respectively. Weight
      loss measurements revealed that the gamma-sterilised acetabular cups exhibited a
      lower wear rate than that by EtO-sterilised. Thc Raman results obtained on gamma
      sterilised and EtO-sterilised acetabular cups showed that the changes in surface
      crystallinity were mainly caused by irradiation rather than by the mechanical
      friction during the in vitro tests.

PMID- 11829438
TI  - The characterisation of human respiratory epithelial cells cultured on resorbable
      scaffolds: first steps towards a tissue engineered tracheal replacement.
AB  - In this study we have used lectin histochemistry and scanning electron microscopy
      (SEM) to assess the growth and characterise the differentiation of human
      respiratory epithelial cells (REC) cultured on two biomaterial scaffolds. The
      first scaffold, based on a hyaluronic acid derivative, was observed to be non
      adhesive for REC. This lack of adhesion was found to be unrelated to the presence
      of the hyaluronic acid binding domain on the surface of isolated REC. The other
      scaffold, consisting of equine collagen. was observed to encourage REC spreading
      and adhesion. Positive Ulex Europaeus agglutinin (UEA) lectin staining of this
      preparation indicated the presence of ciliated REC on the scaffold surface.
      However, the marked decrease in peanut agglutinin (PNA) positive staining,
      relative to that of control cultures and native tissue, indicates a
      dedifferentiation of the secretory cells of the REC monolayer. SEM analysis of
      REC cultured on the collagen scaffold confirmed the presence of ciliated cells
      thereby validating the UEA positive staining. The presence of both established
      and developing cilia was also verified. This study indicates that collagen
      biomaterials are appropriate for the tissue engineering of REC. Furthermore, that
      UEA and PNA staining is a useful tool in the characterisation of cells cultured
      on biomaterials, therefore helpful in identifying biomaterials that are suitable
      for specific tissue engineering purposes.

PMID- 11829440
TI  - Effect of different Ti-6Al-4V surface treatments on osteoblasts behaviour.
AB  - The purpose of the present work was to examine the effect of different Ti-6Al-4V
      surface treatments on osteoblasts behaviour. Previous work in this laboratory has
      demonstrated that an ageing treatment reduces metal ion release from this alloy
      compared to standard passivation procedures. In this study. human osteosarcoma MG
      63 were used in short-term in vitro tests to assay for cell viability and cell
      proliferation at 12, 24 and 72 h while SaOS-2 were used in long-term in vitro
      tests to assay for osteonectin, osteopontin, osteocalcin gene expression, total
      protein amount (TP). alkaline phosphatase activity (ALP) and fibronectin
      production (FN) for 1-4 weeks. Epifluorescence microscopy was used to observe
      SaOS-2 cell morphology. After 24h, there was no difference in MG-63 cell
      viability proliferation or in SaOS-2 cell morphology between the different
      surface treatments. For the long-term tests, the aged Ti-6Al4V induced
      significantly higher cell proliferation than the control Ti-6Al-4V at 72h. At
      week 1, no difference in the osteonectin, osteopontin, and osteocalcin gene
      expression was found between samples. The peak of ALP activity appeared earlier
      at week 2 for the control surface compared with the passivated and aged surfaces.
      The early increase in ALP activity for the control sample could be a compensatory
      effect of decreased osteoblasts proliferation. There was no difference in the
      expression of FN for the different surface treatments. Our present results showed
      that the different surface treatments, which induced different metal ion release
      kinetics and surface properties, influenced the cell proliferation and ALP
      activity of osteoblast cells. Aluminium ions release kinetics as well as presence
      of vanadium ions may play a major role in influencing the osteoblasts behaviour
      in the present study.

PMID- 11829441
TI  - The vascular prosthesis without pseudointima prepared by antithrombogenic
      phospholipid polymer.
AB  - On the luminal surface of the common synthetic vascular prostheses, blood
      coagulation can occur and a thrombus membrane is formed when blood flow passes
      through it. The thrombus membrane should be organized according to the wound
      healing process and it becomes a pseudointima which could serve as a blood
      conduit. However, the small-diameter vascular prosthesis may be quickly occluded
      by the initial thrombus. Therefore, no clinically applicable small-diameter
      prostheses have been developed to date. 2-Methacrylovloxyethyl phosphoryleholine
      (MPC) polymers resemble the structure of an outer cell membrane similar to the
      fluid mosaic model and demonstrate excellent antithrombogenicity. The purpose of
      this study is to develop a clinically applicable small-diameter prosthesis based
      on the new concept of the MPC polymer. We prepared vascular prostheses (2mm ID)
      from polymer blend composed of segmented polyurethane and the MPC polymer. The
      prostheses were placed in rabbit carotid arteries. The luminal surface retrieved
      at eight weeks after implantation was clear without thrombus and pseudointima. We
      now realize that the vascular prosthesis having the MPC polymer can be applied as
      a small-diameter prosthesis because it functions without thrombus and
      pseudointima formation.

PMID- 11829442
TI  - Culture of primary human gingival fibroblasts on biodegradable membranes.
AB  - Repair and regeneration of periodontal tissues by tissue engineering is dependent
      on the use of biodegradable polymer scaffolds which serve as a carrier for cells
      or bioactive substances. There is a need to understand how a specific biomaterial
      may influence gene expression. The aim of this investigation was to develop and
      to optimize an in vitro technique for the adherance and proliferation of primary
      human gingivaL cells on implantable and biodegradable matrices. Square pieces of
      Bio-Gide matrix (BG) and slices of Ethisorb tamponade (ET) were coated with poly
      L-lactide. The stability of coated and uncoated scaffolds was investigated by
      incubation in standard culture medium. Various concentrations of the cells were
      seeded onto coated and uncoated polymer matrices in tissue culture dishes without
      shaking ("static seeding") or continuous shaking ("agitated seeding"). Cultures
      were grown for 4 week and were then evaluated by light and scanning electron
      microscopy. After a culture period of 10 d, BG-carriers showed a delicate
      consistency which made histological processing difficult. Cells were grown only
      sparsely in coated and non-coated BG-scaffolds. Contrary. ET-specimens were
      stable during a 4 week culture period. After "static seeding" a significantly
      higher number of cells resulted in comparison to those in "agitated" cultures.
      The cells were evenly distributed throughout the ET-carriers and produced
      extracellular matrix compounds as well. Furthermore, the examination with RT-PCR
      (reverse transcription-polymerase chain reaction) revealed that the cells
      synthesized and secreted type I collagen, and expressed genes implicated in
      transducing bone morphogenetic protein (BMP) signals. Messenger RNAs for BMP-2, 
      4, -7, the BMP type I receptors Act R-1 (alk 2, activin-like kinase receptor),
      BMPR-IA (alk 3), -IB (alk 6), and the type II receptor BMPR-II were detected.
      These data reveal that static seeding favors the adherence and proliferation of
      primary gingival cells on polyglactin matrices. This system may serve as a
      valuable tool for periodontal tissue engineering.

PMID- 11829443
TI  - The biocompatibility of novel starch-based polymers and composites: in vitro
      studies.
AB  - Studies with biodegradable starch-based polymers have recently demonstrated that
      these materials have a range of properties. which make them suitable for use in
      several biomedical applications, ranging from bone plates and screws to drug
      delivery carriers and tissue engineering scaffolds. The aim of this study was to
      screen the cytotoxicity and evaluate starch-based polymers and composites as
      potential biomaterials. The biocompatibility of two different blends of corn
      starch, starch ethylene vinyl alcohol (SEVA-C) and starch cellulose acetate (SCA)
      and their respective composites with hydroxyapatite (HA) was assessed by
      cytotoxicity and cell adhesion tests. The MTT assay was performed with the
      extracts of the materials in order to evaluate the short-term effect of the
      degradation products. The cell morphology of L929 mouse fibroblast cell line was
      also analysed after direct contact with polymers and composites for different
      time periods and the number of cells adhered to the surface of the polymers was
      determined by quantification of the cytosolic lactate dehydrogenase (LDH)
      activity. Both types of starch-based polymers exhibit a cytocompatibility that
      might allow for their use as biomaterials. SEVA-C blends were found to be the
      less cytotoxic for the tested cell line, although cells adhere better to SCA
      surface. The cytotoxicity test also revealed that SCA and SEVA-C composites have
      a similar response to the one obtained for SCA polymer. Scanning electron
      microscopy (SEM) analysis showed that cells were much more spread on the SCA
      polymer and LDH measurements showed a higher number of cells on this surface.

PMID- 11829444
TI  - Platelet release of transforming growth factor-beta and beta-thromboglobulin
      after in vitro contact with acrylic bone cements.
AB  - Three methacrylate-based bone cements used for the fixation of joint prostheses
      were evaluated: Sulfix-60 (Sulzer Orthopedic Inc., Baar, Switzerland). CMW1
      (DePuy International Ltd., England). and CMW2 (DePuy International Ltd.,
      England). The cements after polymerization were put in contact in vitro with
      platelet-rich plasma. Plasma, in contact only with siliconized glass, was used as
      a negative control. After contact, platelet number. beta-thromboglobulin (beta
      TG), and transforming growth factor-beta1 (TGF-beta1) were determined. The
      Student's paired t test showed that the ccments induced no significant
      modifications of platelet number. CMWI and Sulfix-60 determined a significant
      increase in beta-TG compared with the negative control. All cements determined a
      significant increase in TGF-beta1. Significant differences were also seen in the
      levels of beta-TG and TGF-beta1 between cements with a content of benzoyl
      peroxide < 1 (Sulfix-60) and those with a content > 1 (CMW1 and CMW2). The cement
      with zirconium dioxide (Sulfix-60) produced higher levels of beta-TG and TGF
      beta1, compared to those with barium sulphate (CMW1 and CMW2). In conclusion, all
      the cements induced the secretion of TGF-beta1 CMW1 and Sulfix-60 determined also
      a significant release of beta-TG. Platelet activation induced by the cements from
      one side could contribute to the pathogenesis of deep venous thrombosis, that
      often occurs after prosthetic implant and is caused also by other factors,
      including surgical trauma and venous stasis. From the other side, activated
      platelets can release growth factors favoring bone formation.

PMID- 11829446
TI  - Effects on antibiotic resistance of Staphylococcus epidermidis following adhesion
      to polymethylmethacrylate and to silicone surfaces.
AB  - A number of studies appears to give emphasis to the role of prosthetic materials
      in determining microbial adherence and resistance to host defence and drug
      therapy. Aim of this study was to explore whether the direct contact with
      biomaterial substrata of different chemical nature could influence bacterial
      behaviour, determining possible changes in the bacteria population as far as
      antibiotic resistance is concerned. To this end, susceptibility to penicillin,
      erythromycin, clindamycin, cefamandole, imipenem, vancomycin, ciprofloxacin.
      ampicillin, cefazolin, trimethoprim-sulfamethoxazole, chloramphenicol, amikacin
      and netilmicin was evaluated in a methicillin-, gentamicin- and tobramycin
      resistant Staphylococcus epidermidis strain, after in vitro adhesion to
      polymethylmethacrylate (PM MA) and to silicone elastomer. The susceptibility to
      antibiotics of both adherent bacteria and bacteria which, although exposed to the
      materials, had not undergone adhesion was measured as bacterial growth inhibition
      area onto a plate antibiogram. according to Kirby-Bauer and using an image
      analyser system. The results obtained suggest that the two test materials
      considered in this study were capable to condition bacterial behaviour. In
      particular. the adhesion onto PMMA surfaces induced a marked and significant
      decrease in susceptibility to the following beta-lactam antibiotics: cefamandole
      (32%), cefazolin (23%), imipenem (27%), ampicillin (31%). Moreover, PMMA caused a
      lower but significant reduction in resistance to vancomycin (15%),
      chloramphenicol (16%), amikacin (13%). netilmicin (13%), erythromycin (11%)
      trimethoprim-sulfamethoxazole (13%). In contrast, the adhesion onto silicone
      elastomer appeared to influence bacterial changes to a lesser extent and elicited
      a significant decrease in susceptibility only to cefazolin (10%) and amikacin
      (11). Further studies are required to thoroughly investigate the mechanisms of
      these variations, even though, also according to other authors, one of the best
      conceivable conclusions is that some material substrata can lead to selection of
      variant adhesive bacteria with increased antibiotic resistance.

PMID- 11829445
TI  - Nitric oxide releasing silicone rubbers with improved blood compatibility:
      preparation, characterization, and in vivo evaluation.
AB  - Nitric oxide (NO) releasing silicone rubbers (SR) are prepared via a three-step
      reaction scheme. A diamino triaminoalkyltrimethoxysilane crosslinker is used to
      vulcanize hydroxyl terminated polydimethylsiloxane (PDMS) in the presence of
      ambient moisture and a dibutyltin dilaurate catalyst so that the respective
      diamine triamine groups are covalently linked to the cured SR structure. These
      amine sites are then diazeniumdiolated, in situ, when the cured SR is reacted
      with NO at elevated pressure (80 psi). Although nitrite species are also formed
      during the NO addition reaction, in most cases the diazeniumdiolated polymer is
      the major product within the final SR matrix. Temperature appears to be the major
      driving force for the dissociation of the attached diazeniumdiolate moieties,
      whereas the presence of bulk water bathing the SR materials has only minimal
      effect on the observed NO release rate owing to the low water uptake of the SR
      matrices. The resulting SR films/coatings release NO at ambient or physiological
      temperature for up to 20 d with average fluxes of at least 4 x 10(10) mol x cm(
      2) x min(-1) (coating thickness > or = 600 microm) over first 4 h, comparable to
      the NO fluxes observed from stimulated human endothelial cells. The NO loading
      and concomitant NO release flux of the SR material are readily adjustable by
      altering the diamine triamine loading and film/coating thickness. The new NO
      releasing SR materials are shown to exhibit improved thromboresistance in vivo,
      as demonstrated via reduced platelet activation on the surface of these polymers
      when used to coat the inner walls of SR tubings employed for extracorporeal
      circulation in a rabbit model.

PMID- 11829447
TI  - In vitro cytocompatibility of porcine type I atelocollagen crosslinked by
      oxidized glycogen.
AB  - Oxidized glycogen is used as collagen crosslinker to obtain materials with
      defined crosslinking degrees. These materials are characterized by their swelling
      ratio. calorimetric properties and the crosslinking level. Direct and indirect
      cytotoxicities of the materials obtained as sheets, are evaluated in vitro in
      cultures of human fibroblasts. The crosslinking degree depends on the ratio CHO
      glycogen/NH2 glycogen, but whatever this ratio (4.0, 2.0 or 0.4), an important
      percentage of the introduced CHO groups remains free and these groups are
      responsible for the cytotoxicity observed with the strongly crosslinked
      materials. This cytotoxicity appears in cell shape modification and in
      significant reduction of cell growth. Whatever the crosslinking degree, this
      toxicity can be suppressed by a single treatment with sodium borohydride, which
      reduced the remaining free CHO groups in OH functions and stabilizes the
      materials by a concomitant reduction of the crosslinking imine bonds. After
      reduction, all materials allow cellular adhesion and proliferation. This new
      crosslinking method of the collagen by the oxidized glycogen could be promising
      in the preparation of matrix for in vitro and in vivo tissue regeneration.

PMID- 11829448
TI  - Involvement of tissue transglutaminase in the stabilisation of biomaterial/tissue
      interfaces important in medical devices.
AB  - Tissue transglutaminase (tTG) has recently been established as a novel cell
      surface adhesion protein that binds with high affinity to fibronectin in the
      pericellular matrix. In this study, we have made use of this property to enhance
      the biocompatibility of poly(epsilon-caprolactone) (PCL), a biomaterial currently
      used in bone repair. Poly(epsilon-caprolactone) discs were first coated with
      fibronectin and then tTG. The surface localisation of the two proteins was
      confirmed using ELISA and the tTG shown to be active on the surface by
      incorporation of biotin cadaverine into the fibronectin coating. When human
      osteoblasts (HOBs) were seeded onto the coated polymer surfaces in serum free
      medium, the surface coated with fibronectin and then tTG showed an increase in
      the spreading of the cells as compared to the surface coated with fibronectin
      alone, when analysed using environmental scanning electron microscopy. The
      presence of tTG had no effect on HOB cell differentiation when analysed by
      determining alkaline phosphatase activity. The use of tTG as a novel adhesion
      protein in this way may therefore have considerable potential in forming a stable
      tissue/biomaterial interface for application in medical devices.

PMID- 11829449
TI  - The current management of diabetic dyslipidaemia.
AB  - Compared with non-diabetic individuals, patients with diabetes have a two- to
      four-fold greater risk of myocardial infarction, and growing evidence suggests
      that dyslipidaemia contributes significantly to this excess risk. Based on
      evidence from the major trials of HMG-CoA reductase inhibitors (statins), the
      American Diabetes Association have published updated guidelines that outline
      priorities for the treatment of diabetic dyslipidaemia. These guidelines
      emphasise that low density lipoprotein (LDL) cholesterol is the first priority
      for lipid lowering. All diabetic patients with, or at risk of, coronary heart
      disease (CHD) should be treated to an LDL cholesterol goal of < or = 2.6 mmol/L
      (100 mg/dL). The recent Joint European Task Force on Coronary Prevention
      recommend similar goals: total cholesterol <5.0 mmol/L (190 mg/dL) and LDL
      cholesterol <3.0 mmol/L (115 mg/dL). Both the ADA and Joint European Task Force
      recommend statins as first choice hypolipidaemic therapy for patients with
      diabetic dyslipidaemia. Ongoing trials will provide further evidence of the
      benefits of lipid-lowering therapy with statins in reducing CHD risk in patients
      with type 2 diabetes. Results from these studies will likely add further support
      to the recommendations to use statins in the overall management of diabetic
      patients.

PMID- 11829450
TI  - What does the future hold for diabetic dyslipidaemia?
AB  - Preliminary evidence from trials with the HMG-CoA reductase inhibitors (statins),
      simvastatin and pravastatin, suggests that aggressive treatment of diabetic
      dyslipidaemia will reduce coronary events. Questions regarding the prevention of
      cardiovascular events in diabetic patients are now being addressed in
      prospectively designed trials. The first question is, can aggressive treatment of
      dyslipidaemia lead to primary prevention of cardiovascular events in patients
      with type 2 diabetes? This is being addressed in the ongoing Atorvastatin Study
      for the Prevention of coronary heart disease Endpoints in NIDDM (ASPEN) and the
      Collaborative AtoRvastatin Diabetes Study (CARDS). These trials will randomize
      over 4000 patients with type 2 diabetes and no previous myocardial infarction to
      either atorvastatin or placebo for 4 years. The second question is, are there
      benefits for aggressive lipid lowering to levels below those recommended in
      current treatment guidelines, i.e. is lower better? Results from the recent
      Atorvastatin VErsus Revascularization Treatment (AVERT) trial suggest this to be
      the case. AVERT showed that, in stable coronary heart disease patients who had
      been referred for revascularization, aggressive lowering of low density
      lipoprotein (LDL) cholesterol with atorvastatin 80 mg/day (to a mean level of 2.0
      mmol/L [77 mg/dL]) reduced the incidence of ischaemic events by 36% compared with
      angioplasty and usual care (which reduced LDL cholesterol to 3.1 mmol/L [119
      mg/dL]). The 36% reduction in events with atorvastatin versus angioplasty and
      usual care trended towards significance (p=0.048). The benefits of aggressive
      lipid-lowering therapy are also being investigated in the ongoing Treating to New
      Targets (TNT) and Incremental Decrease in Endpoints through Aggressive Lipid
      lowering (IDEAL) trials. These studies will more closely examine the benefits of
      treating diabetic dyslipidaemia, and will determine how aggressively this
      abnormal lipid profile should be treated.

PMID- 11829451
TI  - CHD: a major burden in type 2 diabetes.
AB  - Patients with type 2 diabetes have a two- to four-fold greater risk of
      cardiovascular mortality than non-diabetic individuals. In order to prevent
      coronary events in the diabetic population, it is important to treat modifiable
      cardiovascular risk factors. Data from the Multiple Risk Factor Intervention
      Trial (MRFIT) show that serum cholesterol level, systolic blood pressure level
      and cigarette smoking were significant predictors of cardiovascular disease
      mortality in men with and without diabetes. At every risk factor level, the
      absolute risk of age-adjusted coronary death rate was three times greater for
      diabetic men than non-diabetic men (p<0.0001). Patients with diabetes have an
      abnormal (dyslipidaemic) lipoprotein profile with high levels of very low density
      lipoprotein cholesterol and triglycerides, and a low level of high density
      lipoprotein cholesterol. Although levels of total cholesterol or low density
      lipoprotein (LDL) cholesterol do not differ significantly between patients with
      and without diabetes, those with diabetes have higher levels of atherogenic small
      dense LDL particles. MRFIT data show that at any serum cholesterol level,
      diabetes confers two-three times the risk for a coronary event. These findings
      constitute the rationale for considering hypolipaemic therapy, e.g. with HMG-CoA
      reductase inhibitors (statins), in diabetic patients with dyslipidaemia,
      particularly in those with evidence of coronary heart disease. Evidence shows
      that statins significantly lower cholesterol, exhibit beneficial effects on many
      components of atherosclerosis, and can significantly reduce the incidence of
      stroke.

PMID- 11829452
TI  - The UKPDS: implications for the dyslipidaemic patient.
AB  - The UK Prospective Diabetes Study (UKPDS) is the largest intervention trial to
      date of patients with type 2 diabetes, involving 5102 newly diagnosed diabetic
      patients. Results showed that 59% of patient deaths were from cardiovascular
      disease. While intensive treatment of glucose produced a significant 25%
      reduction in microvascular endpoints compared with diet only (p=0.0099), patients
      with type 2 diabetes usually have a lipid profile that is highly atherogenic. In
      the UKPDS, intensive treatment of hyperglycaemia and hypertension did not improve
      lipid levels. In patients without diabetes, lipid-lowering therapy has been shown
      to reduce the risk of cardiovascular events in both primary and secondary
      prevention trials. Currently, a number of large-scale trials of lipid-lowering
      therapy in patients with diabetes are ongoing. For example, the Lipids in
      Diabetes Study will determine whether lipid lowering with a statin or fibrate can
      substantially reduce cardiovascular morbidity and mortality in 5000 patients with
      type 2 diabetes. The Atorvastatin Study for the Prevention of coronary heart
      disease ENdpoints (ASPEN) is comparing double-blind treatment with atorvastatin
      and placebo in 2250 US diabetic patients without coronary heart disease, while a
      sister trial in the UK, the Collaborative AtoRvastatin Diabetes Study (CARDS), is
      enrolling 1820 diabetic patients. The results from these trials may provide
      information that which will help determine the future management of diabetic
      dyslipidaemia.

PMID- 11829453
TI  - Cyanide binding to cd(1) nitrite reductase from Pseudomonas aeruginosa: role of
      the active-site His369 in ligand stabilization.
AB  - Cyanide binding to fully reduced Pseudomonas aeruginosa cd(1) nitrite reductase
      (Pa cd(1) NiR) has been investigated for the wild-type enzyme and a site-directed
      mutant in which the active-site His369 was replaced by Ala. This mutation reduces
      the affinity toward cyanide (by approximately 13-fold) and especially decreases
      the rate of binding of cyanide to the reduced d(1) heme (by approximately 100
      fold). The crystal structure of wild-type reduced Pa cd(1) NiR saturated with
      cyanide was determined to a resolution of 2.7 A. Cyanide binds to the iron of the
      d(1) heme, with an Fe-C-N angle of 168 degrees for both subunits of the dimer and
      only His369 is within hydrogen bonding distance of the nitrogen atom of the
      ligand. These results suggest that in Pa cd(1) NiR the invariant distal residue
      His369 plays a dominant role in controlling the binding of anionic ligands and
      allow the discussion of the mechanism of cyanide binding to the wild-type enzyme.

PMID- 11829454
TI  - Mitochondrial genome content is regulated during nematode development.
AB  - Growth and development rely on the mitochondrial respiratory chain (MRC) as the
      major source of ATP. We measured the mitochondrial DNA (mtDNA) copy number of
      each of the Caenorhabditis elegans developmental stages. Embryos, L1, L2, and L3
      larvae all have approximately 25,000 copies of maternally derived mtDNA. The copy
      number increases fivefold in L4 larvae and a further sixfold in adult
      hermaphrodites, but only twofold in adult males. The majority of mtDNA in adult
      worms is germline associated, and germline-deficient mutants show markedly
      reduced mtDNA contents. With sperm-deficient or oocyte-deficient mutants, we
      confirm that mtDNA amplification is primarily associated with oocyte production.
      When mtDNA replication is inhibited, a quantitative and homogeneous arrest as L3
      larvae occurs. Thus, mtDNA amplification is a necessary component of normal
      development and its regulation may involve an energy-sensing decision or
      checkpoint that can be invoked when mitochondrial energy generation is impaired.

PMID- 11829455
TI  - Genetic variants of human beta-defensin-1 and chronic obstructive pulmonary
      disease.
AB  - Chronic obstructive pulmonary disease (COPD) is due to interactions between
      cigarette smoke exposure and other risk factors. Genetic variations of human beta
      defensin-1 (hBD-1), an endogenous antimicrobial peptide in the airway, were
      investigated in 60 patients and 213 healthy volunteers by single-strand
      conformation and restriction fragment length polymorphism analysis and DNA
      sequencing. Four nucleotide variations in the 5' and 3' untranslated regions and
      two nonsynonymous substitutions in the coding region were identified. Of these, a
      newly found Ile38 variant was observed in 15.0% of patients but only in 2.8% of
      healthy individuals and was significantly associated with the disease (OR = 6.1,
      95% confidence intervals 2.0-8.3, P = 0.0012). More than 80% of those with Ile38
      experienced sputum production for more than 3 months during the follow-up period.
      Genetic variations in hBD-1 may define a high-risk subgroup of COPD where the
      component of chronic bronchitis is predominant.

PMID- 11829456
TI  - DNA-binding properties of Mblk-1, a putative transcription factor from the
      honeybee.
AB  - We previously identified a gene, Mblk-1, that encodes a putative transcription
      factor with two DNA-binding motifs expressed preferentially in the honeybee brain
      [H. Takeuchi et al., Insect Mol. Biol. 10, 487-494 (2001)]. In the present study,
      we identified its preferred binding sequence as 5'-CCCTATCGATCGATCTCTACCT-3' and
      characterized its DNA-binding properties using truncated Mblk-1 mutants. An
      electrophoretic mobility shift assay revealed that the full-length Mblk-1 binds
      to the sequence with high affinity, whereas each truncated DNA-binding motif of
      Mblk-1 binds with much lower affinities. An in vitro pull-down assay indicated
      that each DNA-binding motif affords homodimeric bindings, suggesting that Mblk-1
      functions as a dimer.

PMID- 11829457
TI  - In vitro induction of bilirubin conjugation in primary rat hepatocyte culture.
AB  - UDP-glucuronosyltransferase (UGT1A1) is a critical enzyme in the elimination of
      bilirubin. The aim of our study was to investigate bilirubin conjugation in
      primary rat hepatocyte culture and the in vitro inducibility of this isoenzyme by
      inducing compounds of different classes: dexamethasone, clofibrate, rifampicin,
      and methylcholanthrene. Hepatocytes exhibited a marked decline in UGT1A1 activity
      in the first 4 h of culturing (10% of initial activity) and the recovery took 72
      h. Immunoblot analysis proved that the loss of enzyme activity was associated
      with the decrease of protein concentration. Marked induction was detected in the
      cases of dexamethasone, clofibrate, and rifampicin treatments for 96 h both in
      enzyme activity (178, 176, and 168%) and in UGT1A1 protein level (362, 328, and
      250%). The effects of dexamethasone and clofibrate were additive (210%).
      Methylcholanthrene had no influence on bilirubin conjugation in our system.

PMID- 11829458
TI  - Long-term expression after infection by the hybrid vector AdLTR-luc is from
      integrated transgene.
AB  - The novel adenoretroviral vector, AdLTR-luc, infects dividing and nondividing
      cells, and mediates long-term transgene expression(Zheng, C., Baum, B. J.,
      Iadarola, M. J., and O'Connell, B. C., Nat. Biotech. 18, 176-180, 2000). To
      determine the source of this expression we examined two epithelial cell lines.
      One, HSG, permits E1(-) recombinant adenoviral replication, while the other, A5,
      does not. An HSG clone, that expressed luciferase stably for > 6 months, was
      obtained following infection at approximately 0.2 AdLTR-luc particles/cell.
      Southern and PCR analyses showed that luciferase cDNA present was integrated. A5
      cells were infected with AdLTR-luc at approximately 1000 particles/cell, and
      colonies were obtained by limiting dilution. Eight clones showed stable
      luciferase activity for > 9 months. High molecular weight DNA extracts from
      clones were positive for genomic integration by Southern, PCR, and quantitative
      PCR analyses. Similar analyses of low molecular weight DNA extracts indicated the
      absence of intact extrachromosomal vector. These data demonstrate that long-term
      luciferase expression after infection by AdLTR-luc is derived from the integrated
      cDNA.

PMID- 11829459
TI  - WICH, a novel verprolin homology domain-containing protein that functions
      cooperatively with N-WASP in actin-microspike formation.
AB  - We describe a novel protein that contains a verprolin-homology (V) region,
      through which several actin-regulating proteins, including Wiskott-Aldrich
      syndrome protein (WASP) family members, bind directly to actin. The amino acid
      sequence is homologous to the sequences of WASP-interacting protein (WIP) and
      CR16, both of which associate with WASP and/or N-WASP, and thus these three
      proteins constitute a new protein family. We named the protein WICH (WIP- and
      CR16-homologous protein). WICH associates strongly with N-WASP but only weakly
      with WASP via its C-terminal WASP-interacting (W) region. Ectopic expression of
      WICH induces actin-microspike formation through cooperation with N-WASP. In
      addition, expression of the W fragment of WICH suppresses microspike formation
      induced by N-WASP, indicating an essential role for WICH in N-WASP-induced
      microspike formation.

PMID- 11829460
TI  - Polyethylenimine-mediated suicide gene transfer induces a therapeutic effect for
      hepatocellular carcinoma in vivo by using an Epstein-Barr virus-based plasmid
      vector.
AB  - The present study aimed to establish a novel efficient nonviral strategy for
      suicide gene transfer in hepatocellular carcinoma (HCC) in vivo. We employed
      branched polyethylenimine (PEI) and combined it with Epstein-Barr virus (EBV)
      based plasmid vectors. The HCC cells transfected with an EBV-based plasmid
      carrying the herpes simplex virus-1 thymidine kinase (HSV-1 Tk) gene (pSES.Tk)
      showed up to 30-fold higher susceptibilities to ganciclovir (GCV) than those
      transfected with a conventional plasmid vector carrying the HSV-1 Tk gene
      (pS.Tk). The therapeutic effect in vivo was tested by intratumoral injection of
      the plasmids into HuH-7 hepatomas transplanted into C.B-17 scid/scid mutant
      (SCID) mice and subsequent GCV administrations. Treatment with pSES.Tk, but not
      pS.Tk, markedly suppressed growth of hepatomas in vivo, resulting in a
      significantly prolonged survival period of the mice. These findings suggest that
      PEI-mediated gene transfer system can confer efficient expression of the suicide
      gene in HCC cells in vivo by using EBV-based plasmid vectors.

PMID- 11829461
TI  - Pioglitazone prevents early-phase hepatic fibrogenesis caused by carbon
      tetrachloride.
AB  - Here we investigated the effect of pioglitazone, a peroxisome proliferator
      activated receptor (PPAR)-gamma ligand, on early-phase hepatic fibrogenesis in
      vivo caused by acute carbon tetrachloride (CCl(4)) administration in the rat.
      Pioglitazone (1 mg/kg BW) prevented pericentral fibrosis and induction of alpha
      smooth muscle actin (SMA) 72 h after CCl(4) administration (1 ml/kg BW). CCl(4)
      induction of alpha1(I)procollagen mRNA in the liver was blunted by pioglitazone
      to the levels almost 2/3 of CCl(4) alone. Pioglitazone also prevented CCl(4)
      induced hepatic inflammation and necrosis, as well as increases in serum tumor
      necrosis factor-alpha levels. Further, pioglitazone inhibited the induction of
      alphaSMA and type I collagen in primary cultured hepatic stellate cells in a dose
      dependent manner. In conclusion, pioglitazone inhibits both hepatic inflammation
      and activation of hepatic stellate cells, thereby ameliorating early-phase
      fibrogenesis in the liver following acute CCl(4).

PMID- 11829462
TI  - Aberrant expression of centractin and capping proteins, integral constituents of
      the dynactin complex, in fetal down syndrome brain.
AB  - Down syndrome (DS, trisomy 21) is the most frequent genetic cause of mental
      retardation. Although known for more than a hundred years the underlying
      pathomechanisms for the phenotype and impaired brain functions remain elusive.
      Performing protein hunting in fetal DS brain, we detected a series of
      cytoskeleton proteins with aberrant expression in fetal DS cortex. Fetal brain
      cortex samples of controls and DS of the early second trimenon of gestation were
      used for the experiments. We applied two-dimensional electrophoresis with in-gel
      digestion of protein spots, subsequent mass spectroscopical (MALDI)
      identification, and quantification of spots using specific software. Centractin
      alpha, F-actin capping protein alpha-1, alpha-2 and beta subunits were
      significantly reduced in fetal DS cortex, whereas dynein intermediate clear 2,
      dynein intermediate chain 2, and kinesin light chain protein levels were
      unchanged. Centractins and F-actin capping proteins are major determinants of the
      cytoskeleton and are involved in pivotal functions including cellular, organelle,
      and nuclear motility. Deranged centractins and F-actin capping proteins may
      represent or induce deficient axonal transport and may well contribute to
      deterioration of the cytoskeleton's mitotic functions in trisomy 21.

PMID- 11829463
TI  - A significant role for the heme oxygenase-1 gene in endothelial cell cycle
      progression.
AB  - Heme oxygenase (HO) catalyzes the conversion of heme to biliverdin with the
      release of iron and carbon monoxide. HO-1 is inducible by inflammatory
      conditions, which cause oxidative stress in endothelial cells. Overexpression of
      human HO-1 in endothelial cells may have the potential to provide protection
      against a variety of agents that cause oxidative stress. We investigated the
      physiological significance of human HO-1 overexpression, using a retroviral
      vector, on cell cycle progression in the presence and absence of pyrrolidine
      dithiocarbamate (PDTC). The addition of PDTC (25 and 50 microM) to human
      microvessel endothelial cells over 24 h resulted in significant (P < 0.05)
      abnormalities in DNA distribution and cell cycle progression compared to cells
      overexpressing the HO-1 gene. The addition of PDTC resulted in a significantly
      decreased G(1) phase and an increased G(2)/M phase in the control cells, but not
      in cells transduced with the human HO-1 gene (P < 0.05). Further, PDTC had a
      potent effect on DNA distribution abnormalities in exponentially grown cells
      compared to subconfluent cells. Upregulation of HO activity in endothelial cells,
      as a result of overexpressing human HO-1, prevented PDTC-mediated abnormalities
      in DNA distribution. Inhibition of HO activity by tin-mesoporphyrin (SnMP) (30
      microM) resulted in enhancement of PDTC-mediated abnormalities in cell cycle
      progression. Bilirubin or iron did not mediate DNA distribution. We conclude that
      an increase in endothelial cell HO-1 activity with subsequent generation of
      carbon monoxide, elicited by gene transfer, reversed the PDTC-mediated
      abnormalities in cell cycle progression and is thus a potential therapeutic means
      for attenuating the effects of oxidative stress-causing agents.

PMID- 11829464
TI  - Serum bisphenol a concentrations showed gender differences, possibly linked to
      androgen levels.
AB  - To investigate human exposure to bisphenol A (BPA), a widely used endocrine
      disruptor, we measured serum BPA concentrations and analyzed the interrelation of
      BPA with sex-related hormones. BPA was detected in all human sera by a novel
      enzyme-linked immunosorbent assay. Serum BPA concentrations were significantly
      higher in normal men (1.49 +/- 0.11 ng/ml; P < 0.01) and in women with polycystic
      ovary syndrome (1.04 +/- 0.10 ng/ml; P < 0.05) compared with normal women (0.64
      +/- 0.10 ng/ml). There were significant positive correlations between serum BPA
      and total testosterone (r = 0.595, P < 0.001) and free testosterone (r = 0.609, P
      < 0.001) concentrations in all subjects and likewise between serum BPA and total
      testosterone (r = 0.559, P < 0.01) and free testosterone (r = 0.598, P < 0.001)
      concentrations in all female subjects, but not between serum BPA and other sex
      related hormone concentrations in any group. These findings showed that there are
      gender differences in serum BPA concentrations, possibly due to differences in
      the androgen-related metabolism of BPA.

PMID- 11829465
TI  - Inhibition of nuclear transport of caspase-7 by its prodomain.
AB  - Apoptosis is a major form of cell death, characterized by a series of
      morphological changes induced by cleaving cytoplasmic and nuclear proteins via
      active caspases. The data presented here show, by fluorescence microscopic and
      immunoblotting analyses, that a prodomain of caspase-7 inhibits its nuclear
      translocation and apoptosis-inducing activity. This nuclear localization is
      dependent on the presence of a basic tetrapeptide that is conserved in mammalian
      and Xenopus caspase-7 and that is located downstream of a cleavage site between a
      prodomain and a catalytic protease domain. Furthermore, an attachment of the
      caspase-7 prodomain (31 amino acids) represses the nuclear transport of a fusion
      protein of a heterologous protein and the caspase-7 nuclear localization signal
      (19 amino acids), suggesting that the inhibition of nuclear localization by the
      prodomain is mediated by the interaction of these short peptides.

PMID- 11829466
TI  - Identification of rat EMAP, a delta-glutamate receptor binding protein.
AB  - While most subtypes of glutamate receptors have been studied extensively, less is
      known about the delta-glutamate receptors, delta1 and delta2. Although neither
      forms functional channels when expressed in heterologous cells, genetic analyses
      have demonstrated the physiological significance of delta2. We used the cytosolic
      C-terminus of the delta2 glutamate receptor subunit in a yeast two-hybrid screen
      of a rat brain cDNA library to identify delta-glutamate receptor binding
      proteins. We isolated rat EMAP, the rat homolog of a microtubule-associated
      protein initially isolated and characterized in echinoderms. Rat EMAP contains 10
      WD-repeats, which are domains important for mediating protein-protein
      interactions in a wide variety of proteins. Rat EMAP binds to delta-glutamate
      receptor subunits within a 50-amino-acid segment of the delta C-terminus. It is
      widely expressed in both brain and peripheral tissues, including high expression
      in brainstem and enrichment in the postsynaptic density.

PMID- 11829467
TI  - Eukaryotic cell determination of ExoS ADP-ribosyltransferase substrate
      specificity.
AB  - Exoenzyme S (ExoS) ADP-ribosylates multiple low-molecular-mass G- (LMMG-)
      proteins in vitro. Identification of the in vivo substrate specificity of ExoS
      has been hindered by its bacterial contact delivery into eukaryotic cells and
      difficulties in identifying ADP-ribosylated proteins within cells. Two
      dimensional electrophoresis comparisons of substrate modifications by ExoS in
      vitro to that following bacterial translocation into HT-29 epithelial cells
      identified Ras, Ral, and Rab proteins and Rac1 as in vivo substrates of ExoS
      ADPRT activity. Cellular fractionation studies identified a relationship between
      membrane association and efficiency of substrate modification. Moreover, Rac and
      Cdc42 relocalized to the membrane in response to ExoS. Comparisons of substrate
      modification to time of exposure to ExoS identified a progression of substrate
      modification, with Ras, RalA, and Rab5 modified first, followed by Rab8 and 11,
      then Rab7 and Rac1. The data support that intrinsic properties of LMMG-proteins
      and their subcellular localization are determinants of bacterially translocated
      ExoS substrate selectivity.

PMID- 11829468
TI  - NYD-SP6, a novel gene potentially involved in regulating testicular
      development/spermatogenesis.
AB  - Using cDNA microarray hybridization from a human testicular cDNA library, a novel
      gene exhibiting 30-fold difference in expression level between adult and embryo
      human testes was cloned and named NYD-SP6, which was 1858 bp in length with 87%
      nucleotide identity with the mouse homologue sequence. The deduced protein
      structure of NYD-SP6 was found to contain two plant homeodomain (PHD) finger
      domains, believed to be involved in activating transcriptional regulation. Tissue
      distribution analysis using Northern blot indicated that the NYD-SP6 gene was
      expressed in a wide range of tissues, with a high expression level in the testis.
      Its expression in human and mouse testes by in situ hybridization was confined to
      Sertoli cells and the expression was developmentally regulated as demonstrated by
      cDNA microarray, in situ hybridization, and semiquantitative PCR in mouse testes.
      GFP/NYD-SP6 protein was predominantly localized in the nucleus of the transfected
      CHO cells, indicating its role in transcriptional regulation. In contrast, the N
      terminal truncated NYD-SP6 (tNYD-SP6) localized in the nuclear envelope,
      indicating this region function as a nuclear localization signal. Further
      Northern blot analysis of gene expression in patients with spermatogenesis arrest
      revealed that NYD-SP6 was absent in one patient whose spermatogenesis was blocked
      at the stage of spermatocytes. Taken together, these results suggest that the
      putative protein of NYD-SP6 may play an important role in stimulating
      transcription involved in testicular development and/or spermatogenesis.

PMID- 11829469
TI  - Cell surface expression of a specific antigenic site on the catalytic subunit of
      (Na(+) + K(+))-ATPase.
AB  - Structural localization of a peptide region, KRQPRNPKTDKLVNE, in the catalytic
      subunit of (Na(+) + K(+))-ATPase was investigated using a specific antibody
      directed against this peptide in cultured African green monkey kidney CV-1 cells.
      Immunofluorescence staining of frozen cell sections shows that an anti
      KRQPRNPKTDKLVNE antibody (SSA95) interacts with its antigenic site and binds to
      the extracellular side of the cell membrane. Indirect immunofluorescence and flow
      cytometric analyses confirmed the presence of this epitope on intact cell
      surfaces. These results suggest that the KRQPRNPKTDKLVNE region of the (Na(+) +
      K(+))-ATPase is expressed on the cellular membrane surface.

PMID- 11829470
TI  - 3D model of human arylamine N-acetyltransferase 2: structural basis of the slow
      acetylator phenotype of the R64Q variant and analysis of the active-site loop.
AB  - The human arylamine N-acetyltransferase NAT2 is responsible for the
      biotransformation of numerous arylamine drugs and carcinogens. A common
      polymorphism of the NAT2 gene has been associated with susceptibility to drug
      toxicity and various malignancies. In this study, we used the crystal structure
      of the Salmonella typhimurium NAT (StNAT) to construct a high-quality model of a
      catalytic N-terminal region of NAT2 (residues 34-131). We show that this region
      has a similar structure in StNAT and the human isoforms NAT1 and NAT2. Comparison
      of the structures of these three molecules suggests that NATs have an active-site
      loop with a conserved structure, which is involved in substrate recognition. Our
      model is consistent with previous experimental data and provides the first
      plausible structural basis of the effects of a common genetic polymorphism
      (Arg(64)-->Gln) on NAT2 activity.

PMID- 11829471
TI  - Functional vanilloid receptors in cultured normal human epidermal keratinocytes.
AB  - Vanilloid receptor subtype 1, VR1, is an ion channel that serves as a polymodal
      detector of pain-producing chemicals such as capsaicin and protons in primary
      afferent neurons. Here we showed that both capsaicin and acidification produced
      elevations in the intracellular Ca(2+) concentration ([Ca(2+)](i)) in cultured
      human epidermal keratinocytes. The capsaicin- and acidification-evoked increases
      in [Ca(2+)](i) were inhibited by capsazepine, an antagonist to VR1. VR1-like
      immunoreactivity was observed in the cells. These findings suggest that
      functional VR1-like protein is present and functions as a sensor against noxious
      chemical stimuli, such as capsaicin or acidification, in epidermal keratinocytes.

PMID- 11829472
TI  - Ets-1 upregulates matrix metalloproteinase-1 expression through extracellular
      matrix adhesion in vascular endothelial cells.
AB  - Ets-1 is a transcription factor regulating the expression of matrix-degrading
      proteinases and is believed to play a critical role in cell migration and tumor
      invasion. The aim of this study is to investigate the direct induction of ets-1
      with consequential upregulation of collagenase-1 (MMP-1) by cell adhesion to
      extracellular matrix and to identify intracellular signal transduction pathways
      involved in ets-1 induction in cultured endothelial cells. The expressions of ets
      1 mRNA and protein as well as MMP-1 protein were induced by cell adhesion to type
      I collagen and antisense ets-1 oligonucleotides impaired that MMP-1 expression.
      In addition, protein tyrosine kinase (PTK) and protein kinase C (PKC) inhibitors
      abrogated their induction, showing the suppression of focal adhesion kinase
      phosphorylation. These results suggest that ets-1 induced by cell adhesion to
      extracellular matrix directly upregulates MMP-1 expression via PTK and PKC
      activation in cultured endothelial cells.

PMID- 11829474
TI  - Unusual signal peptide directs penicillin amidase from Escherichia coli to the
      Tat translocation machinery.
AB  - The recently described Tat protein translocation system in Escherichia coli
      recognizes its protein substrates by the consensus twin arginine (SRRXFLK) motif
      in the signal peptide. The signal sequence of E. coli pre-pro-penicillin amidase
      bears two arginine residues separated by one aspargine and does not resemble the
      Tat-targeting motif but can nevertheless target the precursor to the Tat pathway.
      Mutational studies have shown that the hydrophobic core region acts in synergism
      with the positive charged N-terminal part of the signal peptide as a Tat
      recognition signal and contributes to the efficient Tat targeting of the pre-pro
      penicillin amidase.

PMID- 11829473
TI  - Involvement of ERK, p38 MAP kinase, and PKC in MHC class II-mediated signal
      transduction in a resting B cell line.
AB  - Substantial evidence suggests that MHC class II molecules play a critical role in
      transducing signals during B cell activation and differentiation. In addition, we
      previously found that cross-linking of MHC class II molecules using anti-MHC
      class II antibodies inhibited NF-kappaB activation in resting B cells isolated
      from mouse spleen. In this study, we investigated the mechanism of anti-MHC class
      II antibody-mediated inhibition of LPS-induced NF-kappaB activation using a
      resting B cell line, 38B9. We found that treatment with a corresponding anti-MHC
      class II antibody reduced the activation of NF-kappaB in LPS-stimulated 38B9
      cells, treatment of the antibody mediated down-regulation of PKC and ERK/p38 MAP
      kinase pathways, and treatment with PKC inhibitors caused down-regulation of ERK
      and p38 MAP kinase activities in LPS-stimulated 38B9 cells. Our results suggest
      that the PKC and ERK/p38 MAP kinase pathways are regulated by anti-MHC class II
      antibodies, and that MHC class II molecules are actively involved in the signal
      transduction pathway in the resting B cell line, 38B9. Consequently, disruption
      of these pathways might contribute to the inhibition of LPS-induced NF-kappaB
      activation in 38B9 cells.

PMID- 11829475
TI  - Hypoxia inhibition of apoptosis induced by tumor necrosis factor-related
      apoptosis-inducing ligand (TRAIL).
AB  - Hypoxia is a common environmental stress. Particularly, the center of rapidly
      growing solid tumors is easily exposed to hypoxic conditions. Thus, tumor cell
      response to hypoxia plays an important role in tumor progression as well as tumor
      therapy. However, little is known about hypoxic effect on apoptotic cell death.
      To examine the effects of hypoxia on TRAIL-induced apoptosis, human lung
      carcinoma A549 cells were exposed to hypoxia and treated with TRAIL protein.
      Hypoxia significantly protected A549 cells from apoptosis induced by TRAIL.
      Western blotting analysis demonstrated that hypoxia increased expression of
      antiapoptotic proteins such as Bcl-2, Bcl-XL, and IAP family members. The
      increase of these antiapoptotic molecules is believed to play an hypoxia-mediated
      protective role in TRAIL-induced apoptosis. Our findings suggest that an increase
      of antiapoptotic proteins induced by hypoxia may regulate the therapeutic
      activity of TRAIL protein in cancer therapy.

PMID- 11829476
TI  - Identification of RNA species in the RNA-toxin complex and structure of the
      complex in Clostridium botulinum type E.
AB  - Clostridium botulinum type E toxin was isolated in the form of a complex with
      RNA(s) from bacterial cells. Characterization of the complexed RNA remains to be
      elucidated. The RNA is identified here as ribosomal RNA (rRNA) having 23S and 16S
      components. The RNA-toxin complexes were found to be made up of three types with
      different molecular sizes. The three types of RNA-toxin complex are toxin bound
      to both the 23S and 16S rRNA, toxin bound to the 16S rRNA and a small amount of
      23S rRNA, and toxin bound only to the 16S rRNA.

PMID- 11829477
TI  - Interaction network of human aminoacyl-tRNA synthetases and subunits of
      elongation factor 1 complex.
AB  - Aminoacyl-tRNA synthetases (ARSs) ligate amino acids to their cognate tRNAs. It
      has been suggested that mammalian ARSs are linked to the EF-1 complex for
      efficient channeling of aminoacyl tRNAs to ribosome. Here we systemically
      investigated possible interactions between human ARSs and the subunits of EF-1
      (alpha, beta, gamma, and delta) using a yeast two-hybrid assay. Among the 80
      tested pairs, leucyl- and histidyl-tRNA synthetases were found to make strong and
      specific interaction with the EF-1gamma and beta while glu-proly-, glutaminyl-,
      alanyl-, aspartyl-, lysyl-, phenylalanyl-, glycyl-, and tryptophanyl-tRNA
      synthetases showed moderate interactions with the different EF-1 subunits. The
      interactions of leucyl- and histidyl-tRNA synthetase with the EF-1 complex were
      confirmed by immunoprecipitation and in vitro pull-down experiments.
      Interestingly, the aminoacylation activities of these two enzymes, but not other
      ARSs, were stimulated by the cofactor of EF-1, GTP. These data suggest that a
      systematic interaction network may exist between mammalian ARSs and EF-1 subunits
      probably to enhance the efficiency of in vivo protein synthesis.

PMID- 11829478
TI  - Mutational analysis of the autoprocessing site of subtilisin YaB-G124A.
AB  - The potential residue at the autoprocessing site for improving processing
      efficiency was evaluated from hydrolysis of 19 cleavage-site-mimicking
      octapeptides, VTTXQTVP (-4 to +4), by the mature subtilisin YaB and YaB-G124A
      mutants. Both enzymes cleaved the octapeptides mainly at two sites, X-Q (A-site)
      and Q-T (B-site), at varied preferences. Based on the results above, Met(-1) of
      YaB-G124A was mutated and, as expected, extracellular enzyme production increased
      with Gln or Ala replacement, but decreased with Ile or Asp substitution. Together
      with previous structural studies, our results suggest that autoprocessing is
      dependent on not only the primary structure, but also the peptide flexibility
      around the processing site. Cleavage at the B-site resulted in a novel YaB mutant
      lacking the N-terminus Gln 1, which led the mutant enzyme to less enzymatic
      activity by 80% and less thermal stability by 20 degrees C, perhaps due to its
      ligation to the high-affinity calcium ion.

PMID- 11829479
TI  - Biphasic oxidation of mitochondrial NAD(P)H.
AB  - The redox state of mitochondrial pyridine nucleotides is known to be important
      for structural integrity of mitochondria. In this work, we observed a biphasic
      oxidation of endogenous NAD(P)H in rat liver mitochondria induced by tert
      butylhydroperoxide. Nearly 85% of mitochondrial NAD(P)H was rapidly oxidized
      during the first phase. The second phase of NAD(P)H oxidation was retarded for
      several minutes, appearing after the inner membrane potential collapse and
      mitochondria swelling. It was characterized by disturbance of ATP synthesis and
      dramatic permeabilization of the inner membrane to pyridine nucleotides. The
      second phase was completely prevented by 0.5 microM cyclosporin A or 0.2 mM EGTA
      or was significantly delayed by 25 microM butylhydroxytoluene or trifluoperazine.
      The obtained data suggest that the second phase resulted from oxidation of the
      remaining NADH via the outer membrane electron transport system of permeabilized
      mitochondria, leading to further oxidation of the remaining NADPH in a
      transhydrogenase reaction.

PMID- 11829480
TI  - Molecular basis of bird respiration: primary hemoglobin structure component from
      Tufted duck (Aythya fuligula, Anseriformes)--role of alpha99Arg in formation of a
      complex salt bridge network.
AB  - The primary structure of the major hemoglobin component, HbA (alpha(A)- and beta
      chain), from Tufted duck (Aythya fuligula) is presented. The separation of the
      globin subunits was achieved by ion exchange chromatography on CM-cellulose in 8
      M urea. The amino acid sequence was determined by automatic Edman degradation of
      native chains as well as tryptic and hydrolytic peptides in a gas-phase
      sequencer. The automated homology model was generated by the protein structure
      modeling package WHAT IF using the crystal structure coordinates of Bar-headed
      goose hemoglobin. The 3D structure prediction enables alpha99Arg and beta101Glu
      to emerge as a new intersubunit contact site not found in the hemoglobin
      structure of any other species. alpha99Arg forms a complex salt bridge network
      involving alpha99Arg-beta101Glu-beta104Arg-beta108Asp. Also the substitution at
      alpha34 --> Ile, alpha38 --> Gln and beta55 --> Leu serves to stabilize the oxy
      structure, leading to higher oxygen affinity.

PMID- 11829482
TI  - Genetic "differences".

PMID- 11829481
TI  - Cell adhesion regulates the plasminogen activator inhibitor-1 gene expression in
      anchorage-dependent cells.
AB  - Plasminogen activator inhibitor-1 (PAI-1) is the primary inhibitor of both tissue
      and urokinase-type plasminogen activators (t-PA, u-PA). PAI-1 also regulates the
      attachment of cells to the adhesive glycoprotein vitronectin (VN). PAI-1 gene
      expression has been observed in various cell types, and many regulatory factors
      have been identified to play a role in PAI-1 gene transcription. The complete
      picture of how the PAI-1 gene is expressed when cells adhere to a culture plate
      has not been fully elucidated. We found that in anchorage-dependent cells, PAI-1
      gene was up-regulated when cells were beginning to attach to a culture dish and
      was down-regulated when cells had attached completely. The PAI-1 gene expression
      was induced only in adhered cells but not in non-adhered cells. The regulation of
      PAI-1 protein was also found in both culture medium and cell lysate when cells
      were attached to a culture dish. Our experiment indicates that vitronectin and
      fibronectin, as components of ECM, may be the factors involved in the regulation
      of PAI-1 gene expression. PAI-1, as an inhibitor of the interaction between
      vitronectin and integrin alphavbeta3, may also be a regulator of its own
      expression.

PMID- 11829483
TI  - The muscular dystrophy with myositis (mdm) mouse mutation disrupts a skeletal
      muscle-specific domain of titin.
AB  - Muscular dystrophy with myositis (mdm) is a recessive mouse mutation that causes
      severe and progressive muscular degeneration. Here we report the identification
      of the mdm mutation as a complex rearrangement that includes a deletion and a
      LINE insertion in the titin (Ttn) gene. Mutant allele-specific splicing results
      in the deletion of 83 amino acids from the N2A region of TTN, a domain thought to
      bind calpain-3 (CAPN3) the product of the human limb-girdle muscular dystrophy
      type 2A (LGMD2A) gene. The Ttn(mdm) mutant mouse may serve as a model for human
      tibial muscular dystrophy, which maps to the TTN locus at 2q31 and shows a
      secondary reduction of CAPN3 similar to that observed in mdm skeletal muscle.
      This is the first demonstration that a mutation in Ttn is associated with
      muscular dystrophy and provides a novel animal model to test for functional
      interactions between TTN and CAPN3.

PMID- 11829484
TI  - Identification of a mutation causing mucopolysaccharidosis type IIIA in New
      Zealand Huntaway dogs.
AB  - Mucopolysaccharidosis type IIIA (MPS IIIA) is an autosomal recessive disease that
      occurs due to a deficiency of heparan sulfate sulfamidase (SGSH). The deficiency
      of SGSH results in the lysosomal accumulation and urinary excretion of the
      glycosaminoglycan heparan sulfate. The clinical severity of MPS IIIA is
      predominantly characterized by severe central nervous system degeneration.
      Naturally occurring MPS IIIA has recently been described in New Zealand Huntaway
      dogs, with similar disease progression and biochemical characteristics observed
      in severely affected MPS IIIA patients. Here, we identify the disease-causing
      mutation in the MPS IIIA Huntaway dog as 708-709insC. The frequency of the 708
      709insC mutation in a sample group of 203 New Zealand Huntaway dogs was
      determined to be 3.8%. The identification of the 708-709insC mutation will permit
      the identification of heterozygous carriers as an initial step toward
      establishing a breeding colony of MPS IIIA dogs for the study of various
      therapeutic strategies targeted to the central nervous system.

PMID- 11829485
TI  - Candidate genes required for embryonic development: a comparative analysis of
      distal mouse chromosome 14 and human chromosome 13q22.
AB  - Mice homozygous for the Ednrb(s-1Acrg) deletion arrest at embryonic day 8.5 from
      defects associated with mesoderm development. To determine the molecular basis of
      this phenotype, we initiated a positional cloning of the Acrg minimal region.
      This region was predicted to be gene-poor by several criteria. From comparative
      analysis with the syntenic human locus at 13q22 and gene prediction program
      analysis, we found a single cluster of four genes within the 1.4-to 2-Mb contig
      over the Acrg minimal region that is flanked by a gene desert. We also found 130
      highly conserved nonexonic sequences that were distributed over the gene cluster
      and desert. The four genes encode the TBC (Tre-2, BUB2, CDC16) domain-containing
      protein KIAA0603, the ubiquitin carboxy-terminal hydrolase L3 (UCHL3), the F
      box/PDZ/LIM domain protein LMO7,and a novel gene. On the basis of their
      expression profile during development, all four genes are candidates for the
      Ednrb(s-1Acrg) embryonic lethality. Because we determined that a mutant of Uchl3
      was viable, three candidate genes remain within the region.

PMID- 11829486
TI  - Pex13, the mouse ortholog of the human peroxisome biogenesis disorder PEX13 gene:
      gene structure, tissue expression, and localization of the protein to
      peroxisomes.
AB  - Pex13 encodes an SH3-containing peroxisomal membrane protein required for the
      import of proteins into peroxisomes. In humans, mutations in PEX13 can disrupt
      peroxisome biogenesis and lead to peroxisomal metabolic dysfunction and
      neurodegenerative disease. We report here on the mouse gene Pex13 and its encoded
      protein. Mouse Pex13 spans 18 kb and consists of four exons. We detected Pex13
      transcripts in all mouse tissues tested, with highest levels in liver and testis.
      The Pex13 open reading frame predicts a 44.5-kDa protein that displays 91%
      sequence identity to the human PEX13 protein. We have localized PEX13 protein to
      peroxisomes in mouse liver and show that this protein also sorts to peroxisomes
      in human skin fibroblasts. These data indicate that the structure and properties
      of the mouse and human PEX13 proteins are almost identical. We infer from these
      findings that targeted disruption of mouse Pex13 would provide an appropriate
      model for the study of PEX13 dysfunction in humans.

PMID- 11829487
TI  - SAGE identification of gene transcripts with profiles unique to pluripotent mouse
      R1 embryonic stem cells.
AB  - The identification of signals that regulate pluripotentiality and self-renewal is
      fundamental to the understanding of stem cell biology. To quantify the
      functionally active genome of pluripotent R1 embryonic stem (ES) cells, we used
      the method of serial analysis of gene expression (SAGE) to sequence a total of
      140,313 SAGE tags. Of 44,569 unique transcripts, 9% matched known genes in the
      nonredundant GenBank database, whereas >35% of the unique tags did not match any
      known mouse sequence. Comparisons of relatively abundant (> or = 20) tags in the
      ES cell SAGE catalog with publicly available SAGE data sets identified 16
      transcripts with an abundance profile unique to pluripotent R1 ES cells. We
      confirmed 12 by RT-PCR including those encoding KLF2, a transcription factor;
      galanin, a hypothalamic neurohormone; BAX, a proapoptotic signaling factor; and
      CDK4 and PAL31, cell cycle progression associated proteins. The data from this
      study provide a starting point for detailed transcriptome analyses of stem cells.

PMID- 11829488
TI  - Evolution of the regulators of G-protein signaling multigene family in mouse and
      human.
AB  - The regulators of G-protein signaling (RGS) proteins are important regulatory and
      structural components of G-protein coupled receptor complexes. RGS proteins are
      GTPase activating proteins (GAPs) of Gi-and Gq-class Galpha proteins, and thereby
      accelerate signaling kinetics and termination. Here, we mapped the chromosomal
      positions of all 21 Rgs genes in mouse, and determined human RGS gene structures
      using genomic sequence from partially assembled bacterial artificial chromosomes
      (BACs) and Celera fragments. In mice and humans, 18 of 21 RGS genes are either
      tandemly duplicated or tightly linked to genes encoding other components of G
      protein signaling pathways, including Galpha, Ggamma, receptors (GPCR), and
      receptor kinases (GPRK). A phylogenetic tree revealed seven RGS gene subfamilies
      in the yeast and metazoan genomes that have been sequenced. We propose that
      similar systematic analyses of all multigene families from human and other
      mammalian genomes will help complete the assembly and annotation of the human
      genome sequence.

PMID- 11829490
TI  - A 3-Mb map of a large Segmental duplication overlapping the alpha7-nicotinic
      acetylcholine receptor gene (CHRNA7) at human 15q13-q14.
AB  - Several neuropsychiatric disorders map to human 15q13-q14, which contains a
      strong candidate in the alpha7-nicotinic acetylcholine receptor subunit gene
      (CHRNA7) and is partly duplicated, complicating further genetic analysis. We have
      shown that the partial duplication is in a hybrid (CHRFAM7A)between CHRNA7 and
      one of many copies of a novel gene (FAM7A). We have constructed a 3-Mb map of
      15q13-q14 showing that CHRFAM7A is part of a large segmental duplication in the
      opposite orientation to CHRNA7 and revealing several other duplications. The data
      support a model of recent evolutionary events including duplications, at least
      one large deletion, and an inversion. We have identified two individuals with a
      structure that lacks CHRFAM7A and therefore predates many steps in this model,
      suggesting an unstable region with other intermediates possibly still in
      existence. This instability may be relevant to the many neuropsychiatric
      disorders that map in this region.

PMID- 11829489
TI  - Molecular genetic studies of human chromosome 7 in Russell-Silver syndrome.
AB  - Russell-Silver syndrome (RSS) is a form of congenital short stature characterized
      by severe growth retardation and variable dysmorphic features. In some RSS
      individuals, alterations in imprinted genes may be involved because approximately
      7% of sporadic patients have been observed to have maternal uniparental disomy
      (mUPD) of chromosome 7. RSS patients with structural abnormalities of chromosome
      7 have also been described. In these individuals the chromosome rearrangement
      could disrupt the balance of imprinted genes, contribute to a recessive form of
      RSS, or lead to haploinsufficiency of a crucial developmental gene product.
      Because the mechanism and molecular defects on chromosome 7 causing RSS are still
      unknown, we tested our collection of 77 RSS families for mUPD7 and were able to
      identify three new cases. We also characterized two RSS patients with de novo
      cytogenetic abnormalities involving the short arm of chromosome 7. One had a
      partial duplication [46, XX, dup(7)(p12 p14)] and the second contained a
      paracentric inversion [46, XY, inv(7)(p14 p21)]. Fluorescence in situ
      hybridization (FISH) mapping revealed that the breakpoints on 7p14 were localized
      to the same novel gene, C7orf10, which encompasses >700 kb of DNA. We also
      identified other transcription units from this immediate region, but all seem to
      be biallelically expressed when using a somatic cell hybrid assay.

PMID- 11829491
TI  - Genomic analysis of human chromosome 10q and 4q telomeres suggests a common
      origin.
AB  - The subtelomeric region of human chromosome 4q contains the locus for
      facioscapulohumeral muscular dystrophy (FSHD). The FSHD mutation is a deletion
      within an array of 3.3-kb tandem repeats (D4Z4). The disease mechanism is unknown
      but is postulated to involve position effect. A closely related 3.3-kb array on
      chromosome 10qter, in contrast, is not associated with a disease phenotype. We
      show here that the 4q homology on chromosome 10 is not confined to the 3.3-kb
      repeats but extends both proximally (42 kb) and distally to include the telomere.
      We have also identified the most distal expressed gene on 10q known so far,
      mapping only 96 kb from the 3.3-kb repeat array. A 4q variant has also been
      identified; there is 92%nucleotide identity between the two 4q forms, 4qA and
      4qB. The 4qter and 10qter forms show homology to other chromosome ends, including
      4p, 21q, and 22q, and these regions may represent a relatively common
      subtelomeric domain.

PMID- 11829493
TI  - Identification and characterization of a dense cluster of placenta-specific
      cysteine peptidase genes and related genes on mouse chromosome 13.
AB  - Genes encoding novel murine cysteine peptidases of the papain family C1A and
      related genes were cloned and mapped to mouse chromosome 13, colocalizing with
      the previously assigned cathepsin J gene. We constructed a <460-kb phage
      artificial chromosome (PAC) contig and characterized a dense cluster comprising
      eight C1A cysteine peptidase genes, cathepsins J, M, Q, R, -1, -2, -3, and -6;
      three pseudogenes of cathepsins M, -1, and -2; and four genes encoding putative
      cysteine peptidase inhibitors related to the proregion of C1A peptidases
      (trophoblast-specific proteins alpha and beta and cytotoxic T-lymphocyte
      associated proteins 2alpha and -beta). Because of sequence homologies of 61.9
      72.0% between cathepsin J and the other seven putative cysteine peptidases of the
      cluster, these peptidases are classified as "cathepsin J-like". The absence of
      cathepsin J-like peptidases and related genes from the human genome suggests that
      the cathepsin J cluster arose by partial and complete gene duplication events
      after the divergence of primate and rodent lineages. The expression of cathepsin
      J-like peptidases and related genes in the cluster is restricted to the placenta
      only. Clustered genes are induced at specific time points, and their expression
      increases toward the end of gestation. The specific expression pattern and high
      expression level suggest an essential role of cathepsin J-like peptidases and
      related genes in formation and development of the murine placenta.

PMID- 11829492
TI  - Insertional mutagenesis of the mouse acid ceramidase gene leads to early
      embryonic lethality in homozygotes and progressive lipid storage disease in
      heterozygotes.
AB  - Ceramide is an important cellular lipid involved in signal transduction and the
      biosynthesis of complex sphingolipids. It can be hydrolyzed into sphingosine,
      another important signaling lipid, by the activity of ceramidases. Point
      mutations in the gene (Asah1) encoding one ceramidase, acid ceramidase (AC), lead
      to the lysosomal storage disorder Farber disease (FD). To investigate the role of
      AC in mammalian development, we disrupted the mouse gene Asah1 in embryonic stem
      cells by homologous recombination mediated insertion of an AC targeting vector
      into the wild-type sequence. Genotype analysis of over 150 offspring or embryos
      from heterozygous intercrosses revealed an absence of Asah1(-/-) individuals at
      embryonic day (E) 8.5 or later, although the ratio of wild-type to Asah1(+/-)
      individuals from these intercrosses was 1:2. Northern blot analysis showed that
      AC expression was turned on early in development, by E7.0, and continued through
      at least E17. In contrast, expression of the related lipid hydrolase, acid
      sphingomyelinase, was shut down by E11. Asah1(+/-) mice survived and lived a
      normal lifespan, but developed a progressive lipid storage disease in several of
      their organs, particularly the liver. These histopathological findings in
      Asah1(+/-) animals correlated with an up to twofold increase in the ceramide
      content of these tissues and a reduction n AC activity, confirming that the gene
      insertion event disrupted AC activity and ceramide metabolism. These results
      provide direct in vivo evidence that normal ceramide metabolism, and AC activity
      in particular, is essential for mammalian development. The animals and embryos
      described here should be a valuable resource for investigators studying the role
      of ceramide in cell growth and development, as well as those interested in the
      pathogenesis of FD and other sphingolipid storage disorders.

PMID- 11829494
TI  - Conservation of the T-cell receptor alpha/delta linkage in the teleost fish
      Tetraodon nigroviridis.
AB  - T-cell specific receptors (TCR) are present in all groups] from the jawed
      vertebrates to the mammals. In teleosts, however, the genes encoding the gamma-
      and delta-chains have not yet been found, the alpha- and beta-chains have been
      characterized mainly at the expression level, and genomic organization of these
      loci remains largely unknown. Here we describe both the genomic organization of
      the TCR alpha/delta locus in Tetraodon nigroviridis and the transcription of TCRA
      and TCRD. The TCR alpha/delta locus consists of 13 V alpha/delta segments, a
      Calpha gene, and 12 Jalpha segments, followed by a Cdelta gene, two Jdelta
      segments, and several Ddelta segments. However, the genomic organization found in
      this teleost differs significantly from that which has been observed in mammals
      and birds: a common set of V segments is used to generate either an alpha- or a
      delta-chain by genomic inversion, and the size of the locus is small in this
      vertebrate.

PMID- 11829495
TI  - Molecular cloning of SLC26A7, a novel member of the SLC26 sulfate/anion
      transporter family, from high endothelial venules and kidney.
AB  - A unique characteristic of endothelial cells from high endothelial venules
      (HEVEC) in lymphoid organs and chronically inflamed tissues is their capacity to
      incorporate large amounts of sulfate into sialomucin-type counter-receptors for
      the lymphocyte homing receptor L-selectin. We have previously shown that HEVEC
      express two functional classes of sulfate transporters: sodium/sulfate
      cotransporters and sulfate/anion exchangers. Here, we report the molecular
      cloning from human HEVEC of a 2.9-kb cDNA encoding SLC26A7, a novel member of the
      SLC26 (solute carrier 26) sulfate/anion exchanger family. SLC26A7 exhibits 30%
      identity with three known sulfate transporters from the SLC26 family: SLC26A2
      (also known as DTDST), SLC26A1 (also known as SAT1), and SLC26A3 (also known as
      DRA). Northern blot analysis revealed specific expression of SLC26A7 mRNA in
      kidney. Alternative splicing and polyadenylation of SLC26A7 pre-mRNA in kidney
      suggest the existence of two protein isoforms, SLC26A7.1 and SLC26A7.2, differing
      in their carboxy termini.

PMID- 11829496
TI  - In silico comparison of the transcriptome derived from purified normal breast
      cells and breast tumor cell lines reveals candidate upregulated genes in breast
      tumor cells.
AB  - Genes that are differentially expressed in tumor tissues are potential diagnostic
      markers and drug targets. The DNA sequence information available in the public
      databases can be used to identify transcripts differentially expressed in cancer.
      We report here the combined use of the ORESTES sequences generated in the
      FAPESP/LICR Human Cancer Genome Project and information available in the UniGene
      and SAGE databases to characterize the transcriptome of normal and breast tumor
      cells. We have identified 154 genes as candidates for overexpression in breast
      tumor cells. Among these, 28 genes have been shown by others to be overexpressed
      in breast or other tumors. Using RT-PCR, we tested 11 candidate genes and found
      that 9 were indeed overexpressed in breast tumor cells.

PMID- 11829497
TI  - Profiling gene expression using onto-express.
AB  - Gene expression profiles obtained through microarray or data mining analyses
      often exist as vast data strings. To interpret the biology of these genetic
      profiles, investigators must analyze this data in the context of other
      information such as the biological, biochemical, or molecular function of the
      translated proteins. This is particularly challenging for a human analyst because
      large quantities of less than relevant data often bury such information. To
      address this need we implemented an automated routine, called Onto-Express
      (http://vortex.cs.wayne.edu:8080), to systematically translate genetic
      fingerprints into functional profiles. Using strings of accession or cluster
      identification numbers, Onto-Express searches the public databases and returns
      tables that correlate expression profiles with the cytogenetic locations,
      biochemical and molecular functions, biological processes, cellular components,
      and cellular roles of the translated proteins. The profiles created by Onto
      Express fundamentally increase the value of gene expression analyses by
      facilitating the translation of quantitative value sets to records that contain
      biological implications.

PMID- 11829498
TI  - Bicelle crystallization: a new method for crystallizing membrane proteins yields
      a monomeric bacteriorhodopsin structure.
AB  - Obtaining crystals of membrane proteins that diffract to high resolution remains
      a major stumbling block in structure determination. Here we present a new method
      for crystallizing membrane proteins from a bicelle forming lipid/detergent
      mixture. The method is flexible and simple to use. As a test case,
      bacteriorhodopsin (bR) from Halobacterium salinarum was crystallized from a
      bicellar solution, yielding a new bR crystal form. The crystals belong to space
      group P2(1) with unit cell dimensions of a=45.0 A, b=108.9 A, c=55.9 A,
      beta=113.58 degrees and a dimeric asymmetric unit. The structure was solved by
      molecular replacement and refined at 2.0 A resolution. In all previous bR
      structures the protein is organized as a parallel trimer, but in the crystals
      grown from bicelles, the individual bR subunits are arranged in an antiparallel
      fashion.

PMID- 11829499
TI  - Bending and flexibility of methylated and unmethylated EcoRI DNA.
AB  - We used cyclization kinetics experiments and Monte Carlo simulations to determine
      a structural model for a DNA decamer containing the EcoRI restriction site. Our
      findings agree well with recent crystal and NMR structures of the EcoRI
      dodecamer, where an overall bend of seven degrees is distributed symmetrically
      over the molecule. Monte Carlo simulations indicate that the sequence has a
      higher flexibility, assumed to be isotropic, compared to that of a "generic" DNA
      sequence. This model was used as a starting point for the investigation of the
      effect of cytosine methylation on DNA bending and flexibility. While methylation
      did not affect bend magnitude or direction, it resulted in a reduction in bending
      flexibility and under-winding of the methylated nucleotides. We demonstrate that
      our approach can augment the understanding of DNA structure and dynamics by
      adding information about the global structure and flexibility of the sequence. We
      also show that cyclization kinetics can be used to study the properties of
      modified nucleotides.

PMID- 11829500
TI  - Lagging strand synthesis in coordinated DNA synthesis by bacteriophage t7
      replication proteins.
AB  - The proteins of bacteriophage T7 DNA replication mediate coordinated leading and
      lagging strand synthesis on a minicircle template. A distinguishing feature of
      the coordinated synthesis is the presence of a replication loop containing double
      and single-stranded DNA with a combined average length of 2600 nucleotides.
      Lagging strands consist of multiple Okazaki fragments, with an average length of
      3000 nucleotides, suggesting that the replication loop dictates the frequency of
      initiation of Okazaki fragments. The size of Okazaki fragments is not affected by
      varying the components (T7 DNA polymerase, gene 4 helicase-primase, gene 2.5
      single-stranded DNA binding protein, and rNTPs) of the reaction over a relatively
      wide range. Changes in the size of Okazaki fragments occurs only when leading and
      lagging strand synthesis is no longer coordinated. The synthesis of each Okazaki
      fragment is initiated by the synthesis of an RNA primer by the gene 4 primase at
      specific recognition sites. In the absence of a primase recognition site on the
      minicircle template no lagging strand synthesis occurs. The size of the Okazaki
      fragments is not affected by the number of recognition sites on the template.

PMID- 11829501
TI  - Characterization of two highly similar Rad51 homologs of Physcomitrella patens.
AB  - The moss Physcomitrella patens, which is a land plant with efficient homologous
      recombination, encodes two Rad51 proteins (PpaRad51.1 and PpaRad51.2). The
      PpaRad51.1 and PpaRad51.2 proteins, which share 94 % identity between them,
      interact with themselves and with each other. Both proteins bind ssDNA and dsDNA
      in a Mg(2+) and pH-dependent manner, with a stoichiometry of one PpaRad51.1
      monomer per 3(+/-1) nt or bp and one PpaRad51.2 monomer per 1(+/-0.5) nt or bp,
      respectively. At neutral pH, a 1.6-fold excess of both proteins is required for
      ssDNA and dsDNA binding. PpaRad51.1 and PpaRad51.2 show ssDNA-dependent ATPase
      activity and efficiently promote strand annealing in a nucleotide-independent but
      in a Mg(2+)-dependent manner. Both proteins promote joint-molecule formation, DNA
      strand invasion and are able to catalyse strand exchange in the presence of
      Mg(2+) and ATP. No further increase in the activities is observed when both
      proteins are present in the same reaction. None of the PpaRad51 gene products
      complement the DNA repair and recombination phenotype of Saccharomyces cerevisiae
      rad51delta mutants. However, PpaRad51.1 confers a dominant-negative DNA repair
      phenotype, and both PpaRad51 proteins reduce the levels of double-strand break
      induced recombination when overexpressed in S. cerevisiae wt cells. These results
      suggest that both PpaRad51 proteins are bona fide Rad51 proteins that may
      contribute, in a different manner, to homologous recombination, and that they
      might replace ScRad51 in a hypothetical yeast protein complex inactivating
      different functions required for recombinational repair.

PMID- 11829502
TI  - Biochemical and crystallographic studies of the Met144Ala, Asp92Asn and His254Phe
      mutants of the nitrite reductase from Alcaligenes xylosoxidans provide insight
      into the enzyme mechanism.
AB  - Dissimilatory nitrite reductase catalyses the reduction of nitrite (NO(2)(-)) to
      nitric oxide (NO). Copper-containing nitrite reductases contain both type 1 and
      type 2 Cu sites. Electron transfer from redox partners is presumed to be mediated
      via the type 1 Cu site and used at the catalytic type 2 Cu centre along with the
      substrate nitrite. At the type 2 Cu site, Asp92 has been identified as a key
      residue in substrate utilisation, since it hydrogen bonds to the water molecule
      at the nitrite binding site. We have also suggested that protons enter the
      catalytic site via Asp92, through a water network that is mediated by His254. The
      role of these residues has been investigated in the blue copper nitrite reductase
      from Alcaligenes xylosoxidans (NCIMB 11015) by a combination of point mutation,
      enzymatic activity measurement and structure determination.In addition, it has
      been suggested that the enzyme operates via an ordered mechanism where an
      electron is transferred to the type 2 Cu site largely when the second substrate
      nitrite is bound and that this is controlled via the lowering of the redox
      potential of the type 2 site when it is loaded with nitrite. Thus, a small
      perturbation of the type 1 Cu site should result in a significant effect on the
      activity of the enzyme. For this reason a mutation of Met144, which is the
      weakest ligand of the type 1 Cu, is investigated. The structures of H254F, D92N
      and M144A have been determined to 1.85 A, 1.9 A and 2.2 A resolution,
      respectively. The D92N and H254F mutants have negligible or no activity, while
      the M144A mutant has 30 % activity of the native enzyme. Structural and
      spectroscopic data show that the loss of activity in H254F is due to the
      catalytic site being occupied by Zn while the loss/reduction of activity in
      D92N/M144A are due to structural reasons. The D92N mutation results in the loss
      of the Asp92 hydrogen bond to the Cu-ligated water. Therefore, the ligand is no
      longer able to perform proton abstraction. Even though the loss of activity in
      H254F is due to lack of catalytic Cu, the mutation does cause the disruption of
      the water network, confirming its key role in proton channel. The structure of
      the H254F mutant is the first case where full occupancy Zn at the type 2 Cu site
      is observed, but despite the previously noted similarity of this site to the
      carbonic anhydrase catalytic site, no carbonic anhydrase activity is observed.
      The H254F and D92N mutant structures provide, for the first time, observation of
      surface Zn sites which may act as a Zn sink and prevent binding of Zn at the
      catalytic Cu site in the native enzyme.

PMID- 11829503
TI  - Crystal structures of the sugar complexes of Streptomyces olivaceoviridis E-86
      xylanase: sugar binding structure of the family 13 carbohydrate binding module.
AB  - The family 10 xylanase from Streptomyces olivaceoviridis E-86 contains a
      (beta/alpha)(8)-barrel as a catalytic domain, a family 13 carbohydrate binding
      module (CBM) as a xylan binding domain (XBD) and a Gly/Pro-rich linker between
      them. The crystal structure of this enzyme showed that XBD has three similar
      subdomains, as indicated by the presence of a triple-repeated sequence, forming a
      galactose binding lectin fold similar to that found in the ricin toxin B-chain.
      Comparison with the structure of ricin/lactose complex suggests three potential
      sugar binding sites in XBD. In order to understand how XBD binds to the xylan
      chain, we analyzed the sugar-complex structure by the soaking experiment method
      using the xylooligosaccharides and other sugars. In the catalytic cleft, bound
      sugars were observed in the xylobiose and xylotriose complex structures. In the
      XBD, bound sugars were identified in subdomains alpha and gamma in all of the
      complexes with xylose, xylobiose, xylotriose, glucose, galactose and lactose. XBD
      binds xylose or xylooligosaccharides at the same sugar binding sites as in the
      case of the ricin/lactose complex but its binding manner for xylose and
      xylooligosaccharides is different from the galactose binding mode in ricin, even
      though XBD binds galactose in the same manner as in the ricin/galactose complex.
      These different binding modes are utilized efficiently and differently to bind
      the long substrate to xylanase and ricin-type lectin. XBD can bind any xylose in
      the xylan backbone, whereas ricin-type lectin recognizes the terminal galactose
      to sandwich the large sugar chain, even though the two domains have the same
      family 13 CBM structure. Family 13 CBM has rather loose and broad sugar
      specificities and is used by some kinds of proteins to bind their target sugars.
      In such enzyme, XBD binds xylan, and the catalytic domain may assume a flexible
      position with respect to the XBD/xylan complex, inasmuch as the linker region is
      unstructured.

PMID- 11829504
TI  - Structure of 2C-methyl-d-erythritol-2,4-cyclodiphosphate synthase involved in
      mevalonate-independent biosynthesis of isoprenoids.
AB  - Isoprenoids are biosynthesized from isopentenyl diphosphate and the isomeric
      dimethylallyl diphosphate via the mevalonate pathway or a mevalonate-independent
      pathway that was identified during the last decade. The non-mevalonate pathway is
      present in many bacteria, some algae and in certain protozoa such as the malaria
      parasite Plasmodium falciparum and in the plastids of higher plants, but not in
      mammals and archaea. Therefore, these enzymes have been recognised as promising
      drug targets. We report the crystal structure of Escherichia coli 2C- methyl-d
      erythritol-2,4-cyclodiphosphate synthase (IspF), which converts 4
      diphosphocytidyl-2C-methyl-d-erythritol 2-phosphate into 2C-methyl-d-erythritol
      2,4-cyclodiphosphate and CMP in a Mg-dependent reaction. The protein forms
      homotrimers that tightly bind one zinc ion per subunit at the active site, which
      helps to position the substrate for direct attack of the 2-phosphate group on the
      beta-phosphate.

PMID- 11829505
TI  - 5-Methylthiopentose: a new substituent on lipoarabinomannan in Mycobacterium
      tuberculosis.
AB  - We have identified and characterised in several strains of Mycobacterium
      tuberculosis a new 5-methylthiopentose substituent on lipoarabinomannan (LAM).
      The 5-methylthiopentose was initially observed in heteronuclear (1)H-(13)C-NMR
      spectra of intact, (13)C-enriched LAM. Oligosaccharides carrying this substituent
      were released from (13)C-enriched LAM and from unlabelled LAM using an endo
      arabinanase from Cellulomonas gellida. The presence of the methylthio group in
      these oligosaccharides was established using NMR, high-resolution Fourier
      transform ion cyclotron resonance mass spectrometry and tandem mass spectrometry
      using a Q-TOF mass spectrometer. The 5-methylthiopentose is linked to a terminal
      mannose in the cap structures of these oligosaccharides as evidenced by tandem
      mass spectrometry and by NMR. We suggest interference with the signal
      transduction mechanisms of infected macrophages as a possible function for this
      newly discovered LAM substituent.

PMID- 11829506
TI  - Distribution of molecular size within an unfolded state ensemble using small
      angle X-ray scattering and pulse field gradient NMR techniques.
AB  - The size distribution of molecules within an unfolded state of the N-terminal SH3
      domain of drk (drkN SH3) has been studied by small-angle X-ray scattering (SAXS)
      and pulsed-field-gradient NMR (PFG-NMR) methods. An empirical model to describe
      this distribution in the unfolded state ensemble has been proposed based on (i)
      the ensemble-averaged radius of gyration and hydrodynamic radius derived from the
      SAXS and PFG-NMR data, respectively, and (ii) a histogram of the size
      distribution of structures obtained from preliminary analyses of structural
      parameters recorded on the unfolded state. Results show that this unfolded state,
      U(exch), which exists in equilibrium with the folded state, F(exch), under non
      denaturing conditions, is relatively compact, with the average size of conformers
      within the unfolded state ensemble only 30-40% larger than the folded state
      structure. In addition, the model predicts a significant overlap in the size
      range of structures comprising the U(exch) state with those in a denatured state
      obtained by addition of 2 M guanidinium chloride.

PMID- 11829507
TI  - Effects of the N2144S mutation on backbone dynamics of a TB-cbEGF domain pair
      from human fibrillin-1.
AB  - The calcium-binding epidermal growth factor-like (cbEGF) module and the
      transforming growth factor beta-binding protein-like (TB) module are the two
      major structural motifs found in fibrillin-1, the extracellular matrix (ECM)
      protein defective in the Marfan syndrome (MFS). An MFS-causing mutation, N2144S,
      which removes a calcium ligand in cbEGF32, does not detectably affect fibrillin-1
      biosynthesis, rate of secretion, processing, or deposition of reducible fibrillin
      1 into the ECM. Since the residue at position 2144 is normally engaged in calcium
      ligation, it is unable to mediate intermolecular interactions. We have shown
      previously that this mutation does not affect the folding properties of the TB or
      cbEGF domains in vitro, but does decrease calcium-binding in cbEGF and TB-cbEGF
      domain constructs. Here, we use NMR spectroscopy to probe the effects of the
      N2144S mutation on backbone dynamic properties of TB6-cbEGF32. Analysis of the
      backbone (15)N relaxation data of wild-type TB6-cbEGF32 has revealed a flexible
      inter-domain linkage. Parallel dynamics analysis of the N2144S mutant has shown
      increased flexibility in the region joining the two domains as well as in the
      calcium-binding site at the N terminus of cbEGF32. This research demonstrates
      that a small change in peptide backbone flexibility, which does not enhance
      proteolytic susceptibility of the domain pair, is associated with an MFS
      phenotype. Flexibility of the TB-cbEGF linkage is likely to contribute to the
      biomechanical properties of fibrillin-rich connective tissue microfibrils, and
      may play a role in the microfibril assembly process.

PMID- 11829508
TI  - Tissue-specific co-expression and in vitro heteropolymer formation of the two
      small branchiostoma intermediate filament proteins A3 and B2.
AB  - The two small intermediate filament (IF) proteins A3 and B2 of the
      cephalochordate Amphioxus were investigated. Blot overlays indicated a
      heterotypic interaction pattern of the recombinant proteins. While the individual
      proteins formed only aggregates, the stoichiometric mixture formed obligatory
      heteropolymeric filaments. Mutant proteins with a single cysteine residue in
      equivalent positions gave rise to filaments that oxidize to the disulfide-linked
      heterodimer, which can again form IF. Thus the A3/B2 filaments, which are
      expressed in the intestinal epithelium, are based on a hetero coiled coil. This
      keratin-like assembly process of A3 plus B2 was unexpected, since previous
      evolutionary tree calculations performed by two laboratories on the various
      Amphioxus IF proteins identified keratin I and II orthologs but left the A/B
      group as a separate branch. We discuss obvious evolutionary aspects of the
      Amphioxus IF multigene family, including the previously made observation that B1,
      the closest relative of B2, forms homopolymeric IF in vitro and is, like
      vertebrate type III proteins, expressed in mesodermally derived tissues.

PMID- 11829509
TI  - Structural clusters of evolutionary trace residues are statistically significant
      and common in proteins.
AB  - Given the massive increase in the number of new sequences and structures, a
      critical problem is how to integrate these raw data into meaningful biological
      information. One approach, the Evolutionary Trace, or ET, uses phylogenetic
      information to rank the residues in a protein sequence by evolutionary importance
      and then maps those ranked at the top onto a representative structure. If these
      residues form structural clusters, they can identify functional surfaces such as
      those involved in molecular recognition. Now that a number of examples have shown
      that ET can identify binding sites and focus mutational studies on their relevant
      functional determinants, we ask whether the method can be improved so as to be
      applicable on a large scale. To address this question, we introduce a new
      treatment of gaps resulting from insertions and deletions, which streamlines the
      selection of sequences used as input. We also introduce objective statistics to
      assess the significance of the total number of clusters and of the size of the
      largest one. As a result of the novel treatment of gaps, ET performance improves
      measurably. We find evolutionarily privileged clusters that are significant at
      the 5% level in 45 out of 46 (98%) proteins drawn from a variety of structural
      classes and biological functions. In 37 of the 38 proteins for which a protein
      ligand complex is available, the dominant cluster contacts the ligand. We
      conclude that spatial clustering of evolutionarily important residues is a
      general phenomenon, consistent with the cooperative nature of residues that
      determine structure and function. In practice, these results suggest that ET can
      be applied on a large scale to identify functional sites in a significant
      fraction of the structures in the protein databank (PDB). This approach to
      combining raw sequences and structure to obtain detailed insights into the
      molecular basis of function should prove valuable in the context of the
      Structural Genomics Initiative.

PMID- 11829510
TI  - Functional attributes of the phosphate group binding cup of pyridoxal phosphate
      dependent enzymes.
AB  - Twenty-four structures of pyridoxal-5'-phosphate (PLP)-dependent enzymes that
      represent five different folds are shown to share a common recognition pattern
      for the phosphate group of their PLP-ligands. All atoms that interact with the
      phosphate group of PLP in these proteins are organized within a two-layer
      structure so that the first interacting layer contains from five to seven atoms
      and parallel with this is a second layer containing from three to seven
      interacting atoms. In order to identify features of the phosphate-binding site
      common to PLP-dependent enzymes, a simple procedure is described that assigns
      relative positions to all interacting atoms unambiguously, such that the networks
      of interactions for different proteins can be compared. On the basis of these
      diagrams for 24 enzyme-cofactor complexes, a detailed comparison of the two-layer
      structures of PLP-dependent enzymes, with both similar and different folds, was
      made. A majority of the structurally defined PLP-dependent proteins use the same
      atom types in analogous "key" positions to bind their PLP-ligands. In some
      instances, proteins use water molecules when a key position is unoccupied. A
      similar two-layer recognition pattern extends to protein recognition of at least
      one other, non-PLP ligand, glucosamine 6-phosphate. We refer to this three
      dimensional recognition pattern as the phosphate-binding cup. In general, the
      phosphate-binding cup provides a very stable anchoring point for PLP. When
      numerous water molecules occur within the cup, however, then the phosphate group
      of PLP participates directly in the enzymatic reactions with inorganic phosphate
      replacing the water molecules of the cup. With glucosamine-6-phosphate synthase,
      the water molecules of the phosphate-binding cup facilitate the entry of
      substrate and the exit of product.

PMID- 11829511
TI  - Protein structure prediction constrained by solution X-ray scattering data and
      structural homology identification.
AB  - Here we perform a systematic exploration of the use of distance constraints
      derived from small angle X-ray scattering (SAXS) measurements to filter candidate
      protein structures for the purpose of protein structure prediction. This is an
      intrinsically more complex task than that of applying distance constraints
      derived from NMR data where the identity of the pair of amino acid residues
      subject to a given distance constraint is known. SAXS, on the other hand, yields
      a histogram of pair distances (pair distribution function), but the identities of
      the pairs contributing to a given bin of the histogram are not known. Our study
      is based on an extension of the Levitt-Hinds coarse grained approach to ab initio
      protein structure prediction to generate a candidate set of C(alpha) backbones.
      In spite of the lack of specific residue information inherent in the SAXS data,
      our study shows that the implementation of a SAXS filter is capable of
      effectively purifying the set of native structure candidates and thus provides a
      substantial improvement in the reliability of protein structure prediction. We
      test the quality of our predicted C(alpha) backbones by doing structural homology
      searches against the Dali domain library, and find that the results are very
      encouraging. In spite of the lack of local structural details and limited
      modeling accuracy at the C(alpha) backbone level, we find that useful information
      about fold classification can be extracted from this procedure. This approach
      thus provides a way to use a SAXS data based structure prediction algorithm to
      generate potential structural homologies in cases where lack of sequence homology
      prevents identification of candidate folds for a given protein. Thus our approach
      has the potential to help in determination of the biological function of a
      protein based on structural homology instead of sequence homology.

PMID- 11829512
TI  - Electrostatics significantly affect the stability of designed homeodomain
      variants.
AB  - The role of electrostatic interactions in determining the stability of designed
      proteins was studied by constructing and analyzing a set of designed variants of
      the Drosophila engrailed homeodomain. Computational redesign of 29 surface
      positions results in a 25-fold mutant with moderate stability, similar to the
      wild-type protein. Incorporating helix dipole and N-capping considerations into
      the design algorithm by restricting amino acid composition at the helix termini
      and N-capping positions yields a ninefold mutant of the initial design (a 23-fold
      mutant of wild-type) that is over 3 kcal mol(-1) more stable than the protein
      resulting from the unbiased design. Four additional proteins were constructed and
      analyzed to isolate the effects of helix dipole and N-capping interactions in
      each helix. Based on the results of urea-denaturation experiments and
      calculations using the finite difference Poisson-Boltzmann method, both classes
      of interaction are found to increase the stability of the designed proteins
      significantly. The simple electrostatic model used in the optimization of
      rotamers by iterative techniques (ORBIT) force-field, which is similar to the
      electrostatic models used in other protein design force-fields, is unable to
      predict the experimentally determined stabilities of the designed variants. The
      helix dipole and N-capping restrictions provide a simple but effective method to
      incorporate two types of electrostatic interactions that impact protein stability
      significantly.

PMID- 11829513
TI  - A structural model for the catalytic cycle of Ca(2+)-ATPase.
AB  - Ca(2+)-ATPase is responsible for active transport of calcium ions across the
      sarcoplasmic reticulum membrane. This coupling involves an ordered sequence of
      reversible reactions occurring alternately at the ATP site within the cytoplasmic
      domains, or at the calcium transport sites within the transmembrane domain. These
      two sites are separated by a large distance and conformational changes have long
      been postulated to play an important role in their coordination. To characterize
      the nature of these conformational changes, we have built atomic models for two
      reaction intermediates and postulated the mechanisms governing the large
      structural changes. One model is based on fitting the X-ray crystallographic
      structure of Ca(2+)-ATPase in the E1 state to a new 6 A structure by cryoelectron
      microscopy in the E2 state. This fit indicates that calcium binding induces
      enormous movements of all three cytoplasmic domains as well as significant
      changes in several transmembrane helices. We found that fluorescein
      isothiocyanate displaced a decavanadate molecule normally located at the
      intersection of the three cytoplasmic domains, but did not affect their
      juxtaposition; this result indicates that our model likely reflects a native E2
      conformation and not an artifact of decavanadate binding. To explain the dramatic
      structural effect of calcium binding, we propose that M4 and M5 transmembrane
      helices are responsive to calcium binding and directly induce rotation of the
      phosphorylation domain. Furthermore, we hypothesize that both the nucleotide
      binding and beta-sheet domains are highly mobile and driven by Brownian motion to
      elicit phosphoenzyme formation and calcium transport, respectively. If so, the
      reaction cycle of Ca(2+)-ATPase would have elements of a Brownian ratchet, where
      the chemical reactions of ATP hydrolysis are used to direct the random thermal
      oscillations of an innately flexible molecule.

PMID- 11829514
TI  - Biopiracy: distrust widens the rich-poor divide.

PMID- 11829515
TI  - Adenosine deaminase gene therapy protocol revisited.

PMID- 11829516
TI  - The nasal epithelium as a factory for systemic protein delivery.
AB  - We have previously shown that recombinant Sendai virus (SeV) produces efficient
      in vivo airway epithelial gene transfer. The ability to produce therapeutic
      levels of circulating proteins following noninvasive gene transfer would have
      widespread clinical application. Here, we compared nose, lung, and skeletal
      muscle for the ability to produce circulating levels of the secreted mouse
      antiinflammatory cytokine interleukin-10 (IL10) following SeV-mediated gene
      transfer. High levels of serum IL10 were obtained from each site with a potency
      order of lung > nose > muscle for a given viral titer. Serum levels from each
      site were within the likely required range for anti-inflammatory effects. The
      combination of a high-efficiency gene transfer agent (SeV) and sites that can be
      assessed noninvasively (nose or lung) may circumvent several current challenges
      to gene therapy.

PMID- 11829517
TI  - New basic membrane-destabilizing peptides for plasmid-based gene delivery in
      vitro and in vivo.
AB  - We have designed new basic amphiphilic peptides, ppTG1 and ppTG20 (20 amino
      acids), and evaluated their efficiencies in vitro and in vivo as single-component
      gene transfer vectors. ppTG1 and ppTG20 bind to nucleic acids and destabilize
      liposomes consisting of 1-palmitoyl-2-oleoylphosphatidylcholine (POPC) and
      cholesterol (3:1 mol/mol) at pH 5 and pH 7. Complexes of plasmid DNA and ppTG1
      gave rise to efficient transfection in a variety of human and murine cell lines
      at low charge ratios ([+/-] between 1 and 2). In cell culture experiments, such
      vectors were superior to the membrane-destabilizing peptide KALA. In comparison
      with cationic lipid-, dendrimer-, and polymer-based transfection agents like
      Superfect, polyethylenimine (PEI), and Lipofectin, ppTG1 vectors showed good
      transfection efficiencies, especially at low DNA doses. Moreover, we demonstrated
      for the first time successful gene transfer in living animals with a single
      component peptide vector. In the mouse, intravenous injection of a luciferase
      expression plasmid complexed with ppTG1 or ppTG20 led to significant gene
      expression in the lung 24 hours after injection. Structure-function studies with
      ppTG1, ppTG20, and sequence variants suggest that the high gene transfer activity
      of these peptides is correlated with their propensity to exist in alpha-helical
      conformation, which seems to be strongly influenced by the nature of the
      hydrophobic amino acids.

PMID- 11829518
TI  - Adenoviral vectors stimulate murine natural killer cell responses and demonstrate
      antitumor activities in the absence of transgene expression.
AB  - Adenoviral vector-mediated gene delivery is currently the focus of many efforts
      to administer therapeutic gene products for the treatment of cancer. Although
      these vectors are replication deficient, they can induce specific immune
      responses against both vector- and transgene-encoded proteins. We have extended
      these findings to determine the level of innate natural killer (NK) cell
      responses to adenoviral vector administration in vivo. Similar to many
      replicating viruses, the vectors induce prominent NK cell activation in mouse
      spleens within 2 days of injection. We also observed these NK cell responses
      regardless of the route of administration. Furthermore, stimulation of NK cells
      by adenoviral vectors is independent of viral gene transcription, as UV
      inactivation of the vectors does not reduce the NK cell response. In contrast,
      heat treatment of the vectors destroys their ability to activate NK cells,
      demonstrating the necessity for intact vector particles. In addition, we found
      that administration of "empty" (no transgene) adenoviral vectors delays tumor
      growth in mice bearing B16 melanomas, and this effect is abrogated by depletion
      of NK cells. Collectively, these results demonstrate in a murine system that the
      adenoviral vector gene delivery system itself stimulates NK cells, and this in
      turn can nonspecifically enhance antitumor immunity.

PMID- 11829519
TI  - A deviant immune response to viral proteins and transgene product is generated on
      subretinal administration of adenovirus and adeno-associated virus.
AB  - The immune response after ocular exposure to foreign antigens varies
      substantially from that of a typical systemic response. Anterior chamber
      associated immune deviation (ACAID) has been well documented. The immune response
      of the subretinal space has not been studied in as much detail. Here, we
      characterized the immune response of the subretinal space when it encounters the
      antigens AdV-GFP and AAV-GFP (recombinant adenovirus or adeno-associated virus,
      respectively), each delivering the reporter gene encoding green fluorescent
      protein (GFP). Results indicate that the subretinal space possesses an immune
      deviant property similar to ACAID. AdV-elicited immune responses following
      subretinal injections are significantly reduced compared with systemic responses
      elicited by intradermal injections of the same virus. Furthermore, subretinal AdV
      administration results in transduction of retinal pigment epithelial cells (RPE),
      which are the potential antigen presenting cells of the retina. This subsequently
      generates a population of immunosuppressive Th2-type, cytokine-secreting, splenic
      T cells. This response may be advantageous to the development of ocular gene
      therapy.

PMID- 11829520
TI  - Mechanisms of in vivo DNA electrotransfer: respective contributions of cell
      electropermeabilization and DNA electrophoresis.
AB  - Efficient cell electrotransfection can be achieved using combinations of high
      voltage (HV; 800 V/cm, 100 micros) and low-voltage (LV; 80 V/cm, 100 ms) pulses.
      We have developed equipment allowing the generation of various HV and LV
      combinations with precise control of the lag between the HV and LV pulses. We
      injected luciferase-encoding DNA in skeletal muscle, before or after pulse
      delivery, and measured luciferase expression after various pulse combinations. In
      parallel, we determined permeabilization levels using uptake of (51)Cr-labeled
      EDTA. High voltage alone resulted in a high level of muscle permeabilization for
      300 seconds, but very low DNA transfer. Combinations of one HV pulse followed by
      one or four LV pulses did not prolong the high permeabilization level, but
      resulted in a large increase in DNA transfer for lags up to 100 seconds in the
      case of one HV + one LV and up to 3000 seconds in the case of one HV + four LV.
      DNA expression also reached similar levels when we injected the DNA between the
      HV and LV pulses. We conclude that the role of the HV pulse is limited to muscle
      cell permeabilization and that the LV pulses have a direct effect on DNA. In vivo
      DNA electrotransfer is thus a multistep process that includes DNA distribution,
      muscle permeabilization, and DNA electrophoresis.

PMID- 11829521
TI  - Transduction of hepatocytes after neonatal delivery of a Moloney murine leukemia
      virus based retroviral vector results in long-term expression of beta
      glucuronidase in mucopolysaccharidosis VII dogs.
AB  - The use of Moloney murine leukemia virus (MLV)-based retroviral vectors (RV) can
      result in stable in vivo expression in the liver, but these vectors only
      transduce replicating hepatocytes. As newborn animals exhibit rapid growth, we
      evaluated the ability of MLV-based RV to transduce hepatocytes in neonatal dogs.
      I.v. injection of a beta-galactosidase-expressing RV at 3 days after birth
      resulted in transduction of 9% of hepatocytes. Prior treatment with human
      hepatocyte growth factor at 2.5 mg/kg did not increase transduction. Although
      cells from the spleen were also transduced with moderate efficiency, cells from
      other organs were not. Neonatal dogs with mucopolysaccharidosis VII (MPS VII)
      received an i.v.injection of an RV containing the canine beta-glucuronidase
      (cGUSB) cDNA. At several months after transduction, clusters of hepatocytes that
      expressed high levels of cGUSB were present in the liver, which probably derived
      from replication of transduced hepatocytes. At 6 months after transduction, serum
      GUSB levels were 73% that of homozygous normal dogs and were 34% of the peak
      values observed at 1 week. We conclude that neonatal delivery of an MLV-based RV
      results in stable transduction of hepatocytes in dogs. This approach could result
      in immediate correction in patients with an otherwise-lethal genetic deficiency.

PMID- 11829522
TI  - Transduction of human and mouse pancreatic islet cells using a bicistronic
      recombinant adeno-associated viral vector.
AB  - Recent reports indicate successful transduction of pancreatic islets using
      recombinant adeno-associated viral (rAAV) vectors. This advance offers new
      possibilities in rendering islets resistant to rejection and recurrence of
      autoimmune destruction in the setting of islet transplantation as treatment of
      type 1 diabetes. Most gene delivery approaches using islets have thus far
      involved transduction with a single gene. However, the concomitant delivery of
      more than one gene encoding cytoprotective and/or immunoregulatory molecules may
      offer superior clinical utility. Here, we have generated a bicistronic rAAV
      (serotype 2) vector incorporating a viral internal ribosome entry site (IRES),
      derived from polio virus type 1, to allow for translation of two coupled cDNAs
      from a single mRNA transcript. Our study demonstrates the ability of this vector
      to produce significant expression of two reporter proteins in human and mouse
      islets in vitro. This expression did not interfere with beta-cell function.
      Transduction was maintained in vivo following transplantation of mouse islets.
      These data are the first report of efficient islet cell transduction with two
      genes using a single bicistronic rAAV vector and have direct implications for
      strategies aimed at enhancing islet transplant survival.

PMID- 11829523
TI  - Analysis of differential lipofection efficiency in primary and established
      myoblasts.
AB  - In this study we have compared the process of lipid-mediated transfection in
      primary and established myoblasts, in an attempt to elucidate the mechanisms
      responsible for the scarce transfectability of the former. We determined the
      metabolic stability of cytoplasmically injected and lipofected DNA in primary and
      established myoblasts and carried out a comparative time course analysis of
      luciferase reporter-gene expression and DNA stability. The efficiency of the
      transcription-translation machinery of the two cell types was compared by
      intranuclear injection of naked plasmid DNA encoding luciferase. Subcellular
      colocalization of fluorescein-labeled lipopolyplexes with specific endosomal and
      lysosomal markers was performed by confocal microscopy to monitor the
      intracellular trafficking of plasmid DNA during transfection. The metabolic
      stability of plasmid DNA was similar in primary and established myoblasts after
      both lipofection and cytoplasmic injection. In both cell types, lipofection had
      no detectable effect on the rate of cell proliferation. Confocal analysis showed
      that nuclear translocation of transfected DNA coincided with localization in a
      compartment devoid of endosome- or lysosome-specific marker proteins. The
      residency time of plasmid DNA in this compartment differed for primary and
      established myoblasts. Our findings suggest that the lower transfectability of
      primary myoblasts is mostly due to a difference in the intracellular delivery
      pathway that correlates with more rapid delivery of internalized complex to the
      lysosomal compartment.

PMID- 11829524
TI  - The nonapoptotic pathway mediating thymidine kinase/ganciclovir toxicity is
      reduced by signal from adenovirus type 5 early region 4.
AB  - Suicide gene therapy using thymidine kinase/ganciclovir (Tk/GCV) yields highly
      variable results, in vitro and in vivo. To determine the reasons for such
      variations, we examined cellular mechanisms mediating its cytotoxicity in view of
      their interaction with adenoviral vectors (Ad) used for gene delivery. Here we
      report that the presence of adenovirus early region 4 (AdE4)-encoded viral
      proteins significantly decreases toxicity of Tk/GCV. The E4 region-encoded
      proteins exerted this effect when found on the adenoviral delivery vector and
      when provided in trans in Tk retrovirally transduced cells. The apoptotic
      response was assessed in GCV-treated cells. The decrease in toxicity caused by
      AdE4 proteins was not correlated with apoptotic response, as measured by
      internucleosomal DNA degradation and TUNEL assays. Our results indicate that
      apoptosis is not the only mechanism of Tk/GCV-induced cell death and that other
      mechanisms equally important in determining the success of such a gene therapy
      strategy should be considered when optimizing treatment conditions.

PMID- 11829525
TI  - Targeting angiogenesis and HGF function using an adenoviral vector expressing the
      HGF antagonist NK4 for cancer therapy.
AB  - Hepatocyte growth factor (HGF) affects tumor growth/invasion and tumor
      neovascularization. A proposed HGF antagonist, NK4 (an amino-terminal kringle
      domain peptide of HGF), inhibits tumor growth/invasion through the competition of
      HGF binding to its receptor, c-Met, and acts as an angiogenesis inhibitor. To
      investigate the in vivo effect of NK4 gene transfer, we constructed an adenovirus
      vector expressing human NK4 (AdCMV.NK4). Human lung cancer cell lines (A549 and
      H358) infected in vitro with AdCMV.NK4 yielded NK4 protein without a change in
      the cell growth rate. In contrast, direct injection of AdCMV.NK4 (1 x 10(9) pfu,
      twice) into established subcutaneous tumors in BALB/c nu/nu mice resulted in
      suppression of the tumors by 64% for A549 or by 91% for H358 compared with
      controls (P<0.02 or P<0.01, respectively). Counting of the tumor vessels revealed
      suppressed vascularity by 57% in H358 tumors when using AdCMV.NK4 (P<0.0001).
      Furthermore, systemic NK4 delivery by intraperitoneal injection of AdCMV.NK4
      effectively suppressed both angiogenesis in the Matrigel assay (86% reduction,
      P<0.032), subcutaneous tumor growth in vivo (by 65% for H358, P<0.001), and
      hematogenous lung metastases without obvious side effects. These results indicate
      that NK4 elicits tumor-growth suppression in vivo through its anti-angiogenic
      activity and anti-HGF activity and that NK4 gene transfer can be an effective
      tool in the treatment of cancer.

PMID- 11829526
TI  - Distinct sets of cellular genes control the expression of transfected, nuclear
      localized genes.
AB  - Gene transfection, a process used to study gene function, is itself poorly
      understood. Transfection-enhancing agents, including phorbol myristic acid (PMA)
      and histone deacetylase (HDAC) inhibitors, have been shown to increase
      transfection efficiency either by improving gene delivery into cells or by acting
      directly on delivered DNA sequences to increase their expression. Our results
      indicate that PMA and HDAC inhibitors can also regulate transfection efficiency
      by modulating distinct classes of cellular genes, which otherwise limit or block
      the expression of transfected genes already present in the nucleus. Either HDAC
      inhibitors or PMA was required to express reporter plasmids already present in
      the nucleus of lymphocyte lines. HDAC inhibitors and PMA seemed to operate
      through "transfection-controlling" cellular genes or gene products, rather than
      acting directly on transfected expression plasmids. PMA appeared to increase
      transfection efficiency by activating PKC-inducible, immediate-early gene
      products. Conversely, HDAC inhibitors functioned through a non-PKC-dependent
      pathway that required new protein synthesis, potentially acting through the de
      repression of chromosomal genes. Neither delivery across the cell membrane nor
      into the nucleus may be rate-limiting for expressing transfected genes in some
      cell lines. In such cells, the targeted modulation of specific cellular genes may
      be required to efficiently express transfected genes.

PMID- 11829527
TI  - A system for small-molecule control of conditionally replication-competent
      adenoviral vectors.
AB  - Replication-competent adenoviral vectors are potentially far more efficient than
      replication-defective vectors. However, for reasons of safety, there is a need to
      restrict viral replication both spatially, by limiting replication to certain
      cell types, and temporally. To control replication temporally, we have developed
      a system, based on the small-molecule dimerizer rapamycin, for regulating the
      replication of adenoviral vectors. In this system, one adenoviral vector, AdC4,
      expresses transcription factors whose activity is regulated by the non
      immunosuppressive rapamycin analog AP21967. A second vector, Ad(Z12-I-E1aE1b19k),
      contains E1 genes placed downstream of binding sites for the regulated
      transcription factor. Co-infection of several cell lines by the vector pair leads
      to dimerizer-dependent E1 expression and an increase in viral replication, as
      shown by Southern blots and replication assays. Furthermore, expression of a
      reporter gene from a replication-defective vector, Ad-GM-CSF, can be augmented by
      up to 18-fold by co-infection with the pair of conditionally replicating vectors
      in the presence of dimerizer. Similar results are obtained when the vectors are
      directly injected into subcutaneous HT1080 xenograft tumors in nude mice. We
      believe that vectors based on this principle will be a useful additional tool to
      enhance efficiency and safety of gene delivery for anti-cancer therapy.

PMID- 11829528
TI  - Generation of helper-dependent adenoviral vectors by homologous recombination.
AB  - Helper-dependent adenoviral vectors (HD-Ad) represent a potentially valuable tool
      for safe and prolonged gene expression in vivo. The current approach for
      generating these vectors is based on ligation of the expression cassette into
      large plasmids containing the viral inverted terminal repeats flanking "stuffer"
      DNA to maintain a final size above the lower limit for efficient packaging into
      the adenovirus capsid (approximately 28 kb). The ligation to produce the viral
      plasmid is generally very inefficient. Similar problems in producing first
      generation adenoviral (FG-Ad) vectors were circumvented with the development of a
      system taking advantage of efficient homologous recombination between a shuttle
      plasmid containing the expression cassette and a FG-Ad vector backbone in the
      Escherichia coli strain BJ5183. Here we describe a method for fast and efficient
      generation of HD-Ad vector plasmids that can accommodate expression cassettes of
      any size up to 35 kb. To validate the system, we generated a HD-Ad vector
      expressing the fusion protein between beta-galactosidase and neomycin resistance
      genes under the control of the SR alpha promoter, and one expressing the enhanced
      green fluorescent protein under the control of the cytomegalovirus promoter. The
      viruses were rescued and tested in vitro and for in vivo expression in mice. The
      data collected indicate the possibility for achieving a high level of hepatocyte
      transduction using HD-Ad vectors derived from plasmids obtained by homologous
      recombination in E. coli, with no significant alteration of liver enzymes and a
      less severe, transient thrombocytopenia in comparison with previous reports with
      similar doses of a FG-Ad vector.

PMID- 11829529
TI  - Effects of arginase isoforms on NO Production by nNOS.
AB  - Both arginase isoforms (AI and AII) regulate high-level NO production by the
      inducible NOS, but whether the arginase isoforms also regulate low-level NO
      production by neuronal NOS (nNOS) is not known. In this study, 293 cells that
      stably overexpress nNOS gene (293nNOS cells) were transfected with rat AI (pEGFP
      AI) or AII (pcDNA-AII) plasmids, and nitrite production was measured with or
      without supplemental L-arginine. Transfection with pEGFP-AI increased AI
      expression and activity 10-fold and decreased intracellular l-arginine by 50%.
      Nitrite production was inhibited by >80% when no l-arginine was supplemented but
      not when 1 mM L-arginine was present. The inhibition was reversed by an arginase
      inhibitor, N(omega)-hydroxy-L-arginine. Transfection with pcDNA-AII increased AII
      expression and activity but had little effect on nitrite production even if no l
      arginine was added. These results suggest that, in 293nNOS cells, AI was more
      effective in regulating NO production by nNOS, most likely by competing for L
      arginine.

PMID- 11829530
TI  - Nitric oxide affects the phosphorylation state of microtubule-associated protein
      2 (MAP-2) and neurofilament: an immunocytochemical study in the brain of rats and
      neuronal nitric oxide synthase (nNOS)-knockouts.
AB  - Alterations in function and specific cellular location of cytoskeletal elements
      are characterized by changes in their phosphorylation state. On this background
      we studied immunocytochemically the distribution pattern of neurofilament (NF) in
      its phosphorylated (P-NF) and nonphosphorylated (NP-NF) form and of microtubule
      associated protein-2 (MAP-2) in the rat and mouse brain. Neurons that are
      strongly positive for neuronal nitric oxide synthase (nNOS)-immunoreactivity (IR)
      showed, interestingly, neither P-NF- nor MAP-2-IR. In contrast, nNOS-negative
      neuronal cell elements exhibited an intense IR and specific location for both
      antigens throughout the brain. As a model we chose the dorsolateral tegmental
      nucleus (LDT) of knockout (nNOS(-/-)) mice in which the main splice isoform
      nNOSalpha is lacking, but a low nNOS-activity persists, apparently due to the
      splice isoforms nNOSbeta and gamma. The principal neurons of such nNOS(-/-)-mice,
      which are equivalent to the nNOS-containing neurons in the LDT of wild-type mice
      exhibited a decreased nitrotyrosine-IR and an increased phosphotyrosine-IR if
      compared to those of wild-type mice. The same neurons failed to show NF-IR and
      MAP-2-IR, though. When the residual nNOS activity in nNOS(-/-)-mice was inhibited
      by treatment with N-omega-nitro-L-arginine methyl ester (L-NAME) the principal
      neurons displayed a moderate MAP-2 and NF-staining. NO and NO-derived oxygen
      species are suggested to modulate the balance between the activities of kinases
      and phosphatases, thus changing phosphorylation levels for NF, MAP-2, and,
      possibly, other proteins in neurons and adjacent cell elements.

PMID- 11829531
TI  - Endotoxin-induced liver hypoxia: defective oxygen delivery versus oxygen
      consumption.
AB  - In vivo EPR was used to investigate liver oxygenation in a hemodynamic model of
      septic shock in mice. Oxygen-sensitive material was introduced either (i) as a
      slurry of fine particles which localized at the liver sinusoids (pO2 = 44.39 +/-
      5.13 mmHg) or (ii) as larger particles implanted directly into liver tissue to
      measure average pO2 across the lobule (pO2 = 4.56 +/- 1.28 mmHg). Endotoxin
      caused decreases in pO2 at both sites early (5-15 min) and at late time points (6
      h after endotoxin; sinusoid = 11.22 +/- 2.48 mmHg; lobule = 1.16 +/- 0.42 mmHg).
      The overall pO2 changes observed were similar (74.56% versus 74.72%,
      respectively). Blood pressures decreased transiently between 5 and 15 min (12.88
      +/- 8% decrease) and severely at 6 h (59 +/- 9% decrease) following endotoxin,
      despite volume replacement with saline. Liver and circulatory nitric oxide was
      elevated at these times. Liver oxygen extraction decreased from 44% in controls
      to only 15% following endotoxin, despite severe liver hypoxia. Arterial oxygen
      saturation, blood flow (hepatic artery), and cardiac output were unaffected.
      Pretreatment with l-NMMA failed to improve endotoxin-induced oxygen defects at
      either site, whereas interleukin-13 preserved oxygenation. These site-specific
      measurements of pO2 provide in vivo evidence that the principal cause of liver
      hypoxia during hypodynamic sepsis is reduced oxygen supply to the sinusoid and
      can be alleviated by maintaining sinusoidal perfusion.

PMID- 11829532
TI  - Blood oxygen transport in rats under hypothermia combined with modification of
      the L-Arginine-NO pathway.
AB  - Nitric oxide (NO) has high affinity to heme and by interaction with oxyhemoglobin
      (HbO2) is converted into nitrate to form methemoglobin (MetHb) as a side product.
      In combining with deoxy-Hb NO yields a stable molecule of nitrosyl-hemoglobin
      (HbFe(II)NO) that can further be converted into nitrate and hemoglobin (Hb). In
      addition, Hb was shown to transport NO in a form of S-nitrosohemoglobin (SNO-Hb).
      These features of the Hb and NO interaction are important for blood oxygen
      transport including hemoglobin-oxygen affinity (HOA). The present investigation
      was aimed to study the blood oxygen transport indices (pO2, pCO2, pH, HOA, etc.)
      in rats under hypothermia combined with a modification of L-arginine-NO pathway.
      To modify the L-arginine-NO pathway, rats were administered with N(G)-nitro-L
      arginine methyl ester (L-NAME), L-arginine, or sodium nitroprusside (SNP)
      intravenously before cooling. A substantial impairment of oxygen delivery and
      development of hypoxia, with an important contribution of HOA into the latter
      accompanied the deep hypothermia in rats. All the experimental groups developed
      metabolic acidosis, less pronounced in rats treated with L-arginine only. In the
      experiments with a modification of the L-arginine-NO pathway, an enhanced cold
      resistance, attenuated oxygen deficiency, and a weaker oxyhemoglobin dissociation
      curve (ODC) shift leftwards were observed only after the administration of L
      arginine. Neither SNP nor L-NAME had not any protective effects. L-Arginine
      lowered the value of standard P50 (pO2, corresponding to 50% Hb saturation with
      oxygen at 37 degrees C, pH 7.4, and pCO2 = 40 mmHg). The actual P50 (at actual
      pH, pCO2 and temperature) decreased by approximately 15 mmHg and was
      significantly higher than that under hypothermia without the drug treatment
      (21.03 +/- 0.35 vs 17.45 +/- 0.60 mmHg). NO also can contribute to this system
      through different mechanisms (HOA modification, vascular tone regulation,
      peroxynitrite formation, and effects).

PMID- 11829533
TI  - Role of mitogen-activated protein kinases and tyrosine kinases on IL-1-Induced NF
      kappaB activation and iNOS expression in bovine articular chondrocytes.
AB  - Nitric oxide (NO), produced by the inducible isoform of the NO synthase (iNOS),
      plays an important role in the pathophysiology of arthritic diseases. This work
      aimed at elucidating the role of the mitogen-activated protein kinases (MAPK),
      p38MAPK and p42/44MAPK, and of protein tyrosine kinases (PTK) on interleukin
      1beta (IL-1)-induced iNOS expression in bovine articular chondrocytes. The
      specific inhibitor of the p38MAPK, SB 203580, effectively inhibited IL-1-induced
      iNOS mRNA and protein synthesis, as well as NO production, while the specific
      inhibitor of the p42/44MAPK, PD 98059, had no effect. These responses to IL-1
      were also inhibited by treatment of the cells with the tyrosine kinase
      inhibitors, genistein and tyrphostin B42, which also prevented IL-1-induced NF
      kappaB activation. The p38MAPK inhibitor, SB 203580, had no effect on IL-1
      induced NF-kappaB activation. Finally, the p42/44MAPK inhibitor, PD 98059,
      prevented IL-1-induced AP-1 activation in a concentration that did not inhibit
      iNOS expression. In conclusion, this study shows that (1) PTK are part of the
      signaling pathway that leads to IL-1-induced NF-kappaB activation and iNOS
      expression; (2) the p38MAPK cascade is required for IL-1-induced iNOS expression;
      (3) the p42/44MAPK and AP-1 are not involved in IL-1-induced iNOS expression; and
      (4) NF-kappaB and the p38MAPK lie on two distinct pathways that seem to be
      independently required for IL-1-induced iNOS expression. Hence, inhibition of any
      of these two signaling cascades is sufficient to prevent iNOS expression and the
      subsequent production of NO in articular chondrocytes.

PMID- 11829534
TI  - Nitric oxide and differential effects of ATP on mitochondrial permeability
      transition.
AB  - The mitochondrial permeability transition pore (PTP) undergoes a calcium
      dependent transition (MPT) that disrupts membrane potential and releases
      apoptogenic proteins. Because PTP opening is enhanced by oxidation of thiols at
      the so-called "S-site," we hypothesized that nitrogen monoxide (NO*) could
      enhance the open probability of the PTP, e.g., by S-nitrosylation or S
      thiolation. At low NO donor concentrations (1 to 20 microM), PTP opening in
      succinate-energized liver mitochondria at nonlimiting calcium was delayed or
      unaffected, while it was accelerated by NO donors at 20 to 100 microM. At low
      donor concentrations, PTP opening was facilitated twofold by adenosine
      triphosphate (ATP), which normally delays PTP opening. Among NO donors, the
      oxatriazole GEA 3162, with an activation constant (Ka) of 1.9 microM at 500
      microM ATP was more effective at enhancing pore transition than SIN-1 or SNAP. NO
      donor effects were superseded by diamide, which induces disulfide formation, but
      independent of SH-adduct formation by alkylation. NO-related changes in PTP
      function were accompanied by protein mixed disulfide formation, inhibited by
      dithiothreitol (DTT), and reversed by DTT after donor addition. PTP opening was
      stimulated in the presence of ATP by L-arginine-dependent NO production, i.e.,
      mitochondrial NOS activity. ATP-facilitated pore opening was sensitive to
      atractyloside and depended on nucleotide interactions but not on hydrolysis,
      because specific nonhydrolyzable ATP analogs accelerated pore opening. These data
      indicate NO can influence pore transition by oxidation of thiols that produce
      conformational changes governing the ATP interaction at the adenine nucleotide
      transporter.

PMID- 11829535
TI  - Nitric oxide-mediated protection of A. actinomycetemcomitans-infected murine
      macrophages against apoptosis.
AB  - We investigated apoptotic cell death in murine macrophage cell line J774.1
      following Actinobacillus actinomycetemcomitans infection. Infected macrophages
      generally kill bacteria within phagosomes with nitric oxide (NO). Our previous
      study demonstrated that DNA fragmentation in infected cells increased
      significantly on addition of S-Methylisothiourea (SMT), a selective inhibitor of
      inducible NO synthetase (iNOS). The purpose of the present study was to determine
      the mechanism via which NO affects apoptosis of infected macrophages. J774.1
      cells were infected with A. actinomycetemcomitans Y4 at a bacterium/cell ratio of
      500:1. The infected cells were then cultured in the presence or absence of SMT
      (400 microM). Culture supernatant was removed 21 h after the infection to measure
      LDH activity. Additionally, cellular proteins were extracted from the infected
      cells and measured for histone-associated DNA fragmentation and caspase-1, -3, 
      5, -6, -8, -9 activities. LDH activity and DNA fragmentation were significantly
      elevated by the infection; moreover, levels increased further on addition of SMT.
      Caspase activity of infected cells, particularly caspase-3, was significantly
      higher than that of uninfected cells. Furthermore, caspase activity increased on
      addition of SMT. These findings indicate that NO protects infected J774.1 cells,
      at least in part, against apoptotic cell death via a decrease in caspase
      activity.

PMID- 11829536
TI  - Nitric oxide production in newborns under phototherapy.
AB  - Nitrogen monoxide (NO) is a potent endogenous vasodilator and is involved in
      cytotoxicity, neurotransmission, and immunological defense mechanisms.
      Phototherapy has long been known to change the distribution of blood flow
      throughout the body in newborn infants. The objective of this study was to
      investigate the effect of phototherapy on NO production in otherwise healthy
      newborns. Urinary NO levels were measured before and 6 h after phototherapy by a
      chemiluminescence method using Sievers NOA. Ten newborns (gestational age, 36.4
      +/- 3.9 weeks; birth weight, 2863 +/- 677.44 g; postnatal age, 5.1 +/- 2.72 days)
      were started on phototherapy according to AAP guidelines and urine for NO
      measurement was collected prior to therapy and 6 h after the commencement of
      treatment. Urinary NO levels measured during phototherapy were significantly
      higher (108.8+/-50.69 micromol/mmol creatinine) than the levels measured before
      phototherapy (73.13+/-34.15 micromol/mmol creatinine; P < 0.05). These results
      suggest that newborns receiving phototherapy might have increased NO production,
      which might result in hemodynamic changes. However, further studies on the
      effects of phototherapy on NO and photorelaxation are needed before reaching firm
      conclusions.

PMID- 11829538
TI  - Interleukin-10 inhibition of nitric oxide biosynthesis involves suppression of
      CAT-2 transcription.
AB  - Interleukin-10 (IL-10) has been shown to attenuate lipopolysaccharide (LPS)
      stimulation of inducible nitric oxide synthase (iNOS) in various cell types.
      Guanosine triphosphate cyclohydrolase I (GTPCH) and type-2 cationic amino acid
      transporter (CAT-2) are enzymes that regulate iNOS activity. We therefore sought
      to assess the effects of IL-10 on the expression of these regulatory enzymes in
      LPS-stimulated macrophages that are known to express iNOS. Five minutes after
      adding LPS to these macrophage cultures, various doses of recombinant human IL-10
      were also added. The samples were harvested for analysis 18 h after exposure to
      both LPS and IL-10. In LPS-stimulated macrophages, IL-10 attenuated the
      upregulation of nitric oxide and iNOS protein but not iNOS mRNA. IL-10 also
      attenuated the LPS-induced upregulation of CAT-2 mRNA. However, IL-10 and LPS had
      no effect on GTPCH mRNA expression. We therefore conclude that IL-10 inhibits
      nitric oxide formation in LPS-stimulated macrophages partly by decreasing iNOS
      protein expression. Moreover, our data suggests that transcriptional control of
      CAT-2 plays a role in IL-10 mediated influences upon nitric oxide biosynthesis.

PMID- 11829540
TI  - NO nomenclature?

PMID- 11829537
TI  - Environmental pH regulates LPS-induced nitric oxide formation in murine
      macrophages.
AB  - This study was designed to determine how pH affects nitric oxide (NO) formation
      induced by lipopolysaccharide (LPS) in cultured murine macrophages (RAW 264.7).
      The initial pH of LPS-containing culture media was adjusted to one of eight
      values (6.8, 7.0, 7.2, 7.4, 7.6, 7.8, 8.0, and 8.2). After exposure to LPS for
      eighteen hours, the cultures were harvested for analysis of mRNA, protein, and
      nitrate/nitrite (stable by-products of NO). Analyses for these substances were
      performed using semiquantitative RT-PCR, immunoblotting, and colorimetric Griess
      assays, respectively. We found that acidic culture media favored expression of
      inducible nitric oxide synthase (iNOS) mRNA. However, alkaline media favored
      expression of iNOS protein. Our findings suggest that post-transcriptional
      mechanisms predominate over transcriptional ones in order to regulate pH-mediated
      effects on NO formation by murine macrophages. The optimal pH for NO formation by
      iNOS was found in our study to be around 7.2.

PMID- 11829539
TI  - Dysfunction of soluble guanylyl cyclase in aorta and kidney of Goto-Kakizaki
      rats: influence of age and diabetic state.
AB  - Type 2 diabetes mellitus is frequently associated with arterial hypertension. The
      mechanisms involved in this association are not known in detail, but endothelial
      dysfunction and a blunted vascular response to endogenous vasodilators are
      thought to play a role. In the present study we investigated the in vitro
      activity of vascular and renal soluble guanylyl cyclase in type 2 diabetic Goto
      Kakizaki rats aged 5, 15, and 30 weeks, in comparison with age-matched Wistar
      controls. Blood pressure was monitored by radiotelemetry, and serum glucose and
      insulin concentrations were measured by standard assays. Goto-Kakizaki rats of
      all age groups had serum glucose concentrations significantly higher than those
      of corresponding Wistar controls. Serum insulin was unchanged until 15 weeks of
      age and was elevated in the 30-week-old diabetic rats. Blood pressure in Goto
      Kakizaki rats was significantly higher than that in Wistar controls, and heart
      rate was significantly lower. Mesenteric arteries of diabetic rats showed a
      blunted relaxation in response to acetylcholine and sodium nitroprusside. In
      aortic tissue from Wistar rats an age-dependent increase was found in nitric
      oxide-stimulated cGMP formation, which was absent in the diabetic animals.
      Moreover, the maximum activity of soluble guanylyl cyclase was significantly
      lower in Goto-Kakizaki rats in all age groups studied. In renal tissue no
      differences were found between diabetic and control rats, except at 30 weeks of
      age when Goto-Kakizaki rats showed a significant reduction in basal and
      stimulated guanylyl cyclase activity. In conclusion, the present study shows a
      persistent reduction in vascular nitric oxide-sensitive guanylyl cyclase in Goto
      Kakizaki rats, which occurred shortly after weaning and may contribute to the
      elevation in blood pressure in this strain of genetically diabetic rats.

PMID- 11829541
TI  - The use of 15N-labeled nitric oxide in lung function tests.

PMID- 11829542
TI  - Femoral venous catheterization was associated with increased risk for infection
      and thrombosis in critically ill patients.

PMID- 11829543
TI  - Review: albumin administration is not associated with excess mortality in acutely
      ill patients.

PMID- 11829544
TI  - Review: low-dose dopamine does not prevent acute renal failure or reduce
      mortality or need for hemodialysis.

PMID- 11829545
TI  - An early invasive strategy reduced the incidence of major cardiac events in
      patients with unstable coronary syndromes.

PMID- 11829546
TI  - Abciximab was more effective than tirofiban in preventing ischemic events in
      patients having coronary stenting.

PMID- 11829547
TI  - Review: Some new bolus tPA-derived fibrinolytics are comparable to tPA in acute
      MI, but others increase bleeding.

PMID- 11829548
TI  - Carvedilol reduced mortality and morbidity caused by myocardial infarction in
      patients with left ventricular dysfunction.

PMID- 11829549
TI  - Predischarge coronary angiography was better than exercise testing for reducing
      hospital use after low-risk chest pain.

PMID- 11829550
TI  - Review: extended-duration prophylaxis with heparin prevents deep venous
      thrombosis in hip or knee replacement.

PMID- 11829551
TI  - Long-term and short-term oral anticoagulation therapies were equivalent for
      venous thromboembolism.

PMID- 11829552
TI  - 3 months and 1 year of oral anticoagulant therapy were equivalent for idiopathic
      proximal deep venous thrombosis.

PMID- 11829553
TI  - Review: angiotensin-converting enzyme inhibitors reduce the progression of
      nondiabetic renal disease.

PMID- 11829554
TI  - A home monitoring service was more effective than usual care in patients with
      essential hypertension.

PMID- 11829555
TI  - Salmeterol was not as effective as triamcinolone for persistent asthma.

PMID- 11829556
TI  - Stopping triamcinolone led to treatment failures in patients with persistent
      asthma who were receiving salmeterol and triamcinolone.

PMID- 11829557
TI  - Omalizumab reduced inhaled corticosteroid use and exacerbations in childhood
      allergic asthma.

PMID- 11829558
TI  - Surgery relieved symptoms but decreased survival more than medical treatment in
      gastroesophageal reflux disease.

PMID- 11829559
TI  - Review: cannabinoids and codeine have similar effects on pain relief, but
      cannabinoids commonly cause adverse psychotropic effects.

PMID- 11829560
TI  - Review: cannabinoids control chemotherapy-induced nausea and vomiting but
      increase the risk for side effects.

PMID- 11829562
TI  - Interferon beta-1a decreased the risk for conversion to clinically definite
      multiple sclerosis.

PMID- 11829561
TI  - Review: placebo is better than no treatment for subjective continuous outcomes
      and for treatment of pain.

PMID- 11829563
TI  - Review: antibiotics modestly increase remission rates in acute bacterial
      conjunctivitis.

PMID- 11829564
TI  - Dietary fiber supplementation with psyllium or gum arabic reduced fecal
      incontinence in community-living adults.

PMID- 11829565
TI  - Oseltamivir was safe and effective for prophylaxis of influenza in the frail
      elderly.

PMID- 11829566
TI  - Review: varicella vaccination is effective in children.

PMID- 11829568
TI  - Brief psychodynamic interpersonal therapy after deliberate self-poisoning reduced
      suicidal ideation and deliberate self-harm.

PMID- 11829567
TI  - 17beta-estradiol reduced depressive and somatic symptoms in perimenopausal women.

PMID- 11829569
TI  - Support by another mother and a child-life specialist decreased anxiety in
      mothers of children with chronic illnesses.

PMID- 11829570
TI  - Combining electrocardiography and necrosis biomarkers improved detection of acute
      myocardial infarction in patients with LBBB.

PMID- 11829571
TI  - Helical computed tomographic results indicated small-to-moderate changes in the
      probability of pulmonary embolism.

PMID- 11829572
TI  - Mortality did not vary with sex by 1 year after a first acute myocardial
      infarction.

PMID- 11829573
TI  - Progression of disease in HIV-infected children slowed after the first year of
      life.

PMID- 11829574
TI  - More women with the pelvic girdle syndrome than with other pelvic pain during
      pregnancy had pelvic pain 2 years after delivery.

PMID- 11829575
TI  - Cardiovascular events were increased in high cardiovascular risk patients with
      albuminuria.

PMID- 11829576
TI  - Recall to a general practitioner or to a nurse clinic improved assessment in
      patients with coronary artery disease.

PMID- 11829577
TI  - The Framingham scores overestimated the risk for coronary heart disease in
      Japanese, Hispanic, and Native American cohorts.

PMID- 11829578
TI  - A clinical prediction model did well in diagnosing pediatric group A beta
      hemolytic streptococcal pharyngitis.

PMID- 11829579
TI  - Double blind, you are the weakest link--good-bye!

PMID- 11829580
TI  - Hydrothermally stable ordered mesoporous titanosilicates with highly active
      catalytic sites.
AB  - Mesoporous titanosilicates (MTS-9) are successfully prepared in strong acidic
      media by a two-step synthesis. MTS-9 has an ordered hexagonal structure and
      exhibits superior hydrothermal stability and high catalytic activity for the
      oxidation of the small molecules of phenol and styrene and also of the bulky
      molecule of trimethylphenol.

PMID- 11829582
TI  - Recognition-mediated assembly of nanoparticles into micellar structures with
      diblock copolymers.
AB  - Polystyrene-based diblock copolymers, featuring diaminotriazine functionality on
      one of the blocks were used to assemble complementary uracil-functionalized
      nanoparticles into micellar aggregates. The size of these self-assembled
      aggregates was controlled by block length, as determined in solution (using
      dynamic light scattering), and in thin films (using transmission electron
      microscopy).

PMID- 11829581
TI  - Cold denaturation of the hammerhead ribozyme.
AB  - Cold denaturation is a thermodynamic phenomenon resulting from a difference in
      the heat capacities, DeltaCp, of the folded and unfolded states of a
      macromolecule. Whereas this phenomenon has been extensively studied in proteins,
      it has been thought not to occur in nucleic acids due to a negligible DeltaCp of
      folding. Questioning the validity of this assumption, the low-temperature
      structure of the hammerhead ribozyme, a small catalytic RNA, was investigated by
      circular dichroism spectroscopy. In the presence of 10 mM Mg2+ at pH 5.0 and 40%
      methanol, a cold unfolding event likely corresponding to tertiary structure loss
      was observed with a Tm of -20 degrees C. In 500 mM NaCl at pH 6.6, and 40%
      methanol, large-scale unfolding of the ribozyme at both hot (Tm = 53 degrees C)
      and cold (Tm = -1 degrees C) temperatures occurred. Fitting of these data to a
      two-state model allowed determination of DeltaCp = 3.4 kJ mol-1 K-1,
      corresponding to >/=0.18 kJ K-1 (mol base pair)-1, in good agreement with
      recently published calorimetric values for DNA duplexes. These results constitute
      the first direct observation of cold denaturation of a nucleic acid, and point to
      the importance of DeltaCp terms in the thermodynamics of nucleic acid folding.

PMID- 11829584
TI  - Intermolecular copper-catalyzed carbon [bond] hydrogen bond activation via
      carbene insertion.
AB  - A series of catalysts of general formula TpXCu (TpX = homoscorpionate ligand)
      promote the insertion of :CHCO2Et (ethyl diazoacetate as the carbene source) into
      the C-H bonds of cycloalkanes and cyclic ethers in moderate to high yield. A
      correlation between the steric hindrance of these catalysts and the yield of the
      transformation has been observed.

PMID- 11829583
TI  - From achiral porphyrins to template-imprinted chiral aggregates and further. Self
      replication of chiral memory from scratch.
AB  - The presence of 10-13 M of chiral clusters of aromatic amino acids addresses
      aggregation of opposite-charged achiral porphyrin towards the formation of smart
      chiral assemblies. The latter supramolecular complexes are able to self-propagate
      and transfer their chiral information with a 100% yield. The chiral bias occurs
      through a correlated sequence of induction, memory, and amplification of
      chirality that strongly recalls possible prebiotic scenarios.

PMID- 11829585
TI  - Novel isomerically pure tetrasubstituted allylboronates: stereocontrolled
      synthesis of alpha-exomethylene gamma-lactones as aldol-like adducts with a
      stereogenic quaternary carbon center.
AB  - In spite of their inherent isomerization tendency and low reactivity, 1
      alkoxycarbonyl vinylcopper(I) intermediates from the conjugate addition of
      organocuprates onto acetylenic esters were trapped with very high cis-addition
      selectivity with iodomethylboronic esters in the presence of HMPA. The resulting
      isomerically pure 3,3-disubstituted allylboronates react with aldehydes in a
      highly diastereo- and enantioselective manner, providing alpha-exomethylene gamma
      lactones with a stereogenic quaternary beta-carbon center.

PMID- 11829586
TI  - Atom transfer radical polymerization from cellulose fibers at ambient
      temperature.
AB  - Cellulose fibers have been successfully grafted with poly(methyl acrylate) using
      atom transfer radical polymerization, mediated by Me6-TREN and Cu(I)Br at ambient
      temperature. The initially hydrophilic cellulose was first modified by reacting
      the hydrozyl groups with 2-bromoisobutyryl bromide whereupon methyl acrylate was
      grafted from the surface. The resulting polymer-grafted papers were extremely
      hydrophobic, thetaa = 133 degrees . FT-IR analysis indicates that the amount of
      grafted polymer can be controlled by adding sacrificial initiator to the
      polymerizing system. Size exclusion chromatography of the bulk polymer revealed
      narrow polydispersities and a molecular weight corresponding to the ratio
      [M]:[I].

PMID- 11829587
TI  - NMR characterization of Bronsted acid sites in faujasitic zeolites with use of
      perdeuterated trimethylphosphine oxide.
AB  - The interactions of Bronsted acid sites of H-Y (FAU) with perdeuterated
      trimethylphosphine oxide (TMPO-d9) are studied with a set of high-resolution
      solid-state NMR experiments. Double- and triple-resonance MAS NMR techniques
      (such as CP, TRAPDOR, and REDOR) verify that the lines in the 31P MAS NMR
      spectrum are indeed from TMPO interacting with Bronsted acid sites. Replacement
      of acidic hydrogens in the sodalite cages with sodium cations results in the
      disappearance of one of the peaks, leading to final assignments of the
      resonances.

PMID- 11829588
TI  - Photoswitching of cation complexation with A monoaza-crown dithienylethene
      photochrome.
AB  - A photochromic dithienylethene, bearing a phenyl azacrown as an ionophore and a
      formyl group as an electron-accepting substituent, changes its binding ability
      for Ca2+ by a factor higher than 103 by photoirradiation. This new
      photoionochromic displays a wavelength-dependent competition between fluorescence
      and photocyclization assigned to a red-shifted absorption of the fluorescing
      conformer compared to the absorption of the photoreactive conformer.

PMID- 11829589
TI  - Indium(III) chloride-sodium borohydride system: a convenient radical reagent for
      an alternative to tributyltin hydride system.
AB  - The indium hydride generated from NaBH4 and InCl3, is a promising candidate of
      alternative to Bu3SnH. In particular, the catalytic performance of InCl3 in the
      dehalogenation of alkyl and aryl halides, intramolecular cyclization and
      intermolecular coupling reaction are noteworthy.

PMID- 11829590
TI  - A reduced polyoxomolybdenum borophosphate anion related to the Wells-Dawson
      clusters.
AB  - The new compound (C3N2H5)8[MoV5MoVI7O22(BO4)2(PO4)5(HPO4)3].nH2O is the first
      molybdenum borophosphate. It contains clusters of twelve molybdenum, eight
      phosphorus and two boron atoms, [Mo12O22(BO4)2(PO4)5(HPO4)3]8- similar to the
      Wells-Dawson clusters. Five molybdenum atoms are MoV while the others are MoVI,
      and the five electrons are delocalized. According to the temperature dependence
      of the magnetic susceptibility four of these electrons are paired.

PMID- 11829591
TI  - Differential minor groove interactions between DNA polymerase and sugar backbone
      of primer and template strands.
AB  - DNA polymerases are the key enzymes for DNA synthesis involved in DNA
      replication, recombination, and repair. These enzymes undergo manifold contacts
      with the primer-template-substrates reaching up to several nucleotide pairs
      beyond the catalytic centre. To evaluate these enzyme contacts with the DNA
      substrates we applied novel synthetic steric probes in functional studies. We
      found that through application of the these probes valuable insights into DNA
      polymerase function can be gained, which might be useful for the design of new
      DNA polymerase-based nucleotide variation detection strategies.

PMID- 11829592
TI  - Coordination of adenosylmethionine to a unique iron site of the [4Fe-4S] of
      pyruvate formate-lyase activating enzyme: a Mossbauer spectroscopic study.
AB  - Pyruvate formate-lyase activating enzyme (PFL-AE) generates the catalytically
      essential glycyl radical of PFL. It is a member of the so-called "radical-SAM
      superfamily" of enzymes that use a [4Fe-4S] cluster and S-adenosylmethionine
      (AdoMet or SAM) to catalyze diverse radical-mediated reactions. Evidence suggests
      that this class of enzymes operate by common initial steps involving the
      generation of an AdoMet-derived adenosyl radical intermediate, of which the
      mechanism remains unresolved. The three-cysteine CX3CX2C cluster-binding motif
      common to all members of this superfamily suggests a unique Fe site in the [4Fe
      4S] cluster, which presumably interacts with AdoMet to effect the reductive
      cleavage and radical generation. Here we employ a dual-iron-isotope (56Fe/57Fe)
      approach to demonstrate the existence of a unique Fe site in the [4Fe-4S] cluster
      of PFL-AE by Mossbauer spectroscopy. Coordination of AdoMet to this unique Fe
      site was made evident by the observation of a substantial increase in the isomer
      shift (delta) of the Mossbauer spectrum associated with the unique Fe site: delta
      = 0.42 mm/s in the absence of AdoMet increases to delta = 0.72 mm/s in the
      presence of AdoMet. Further, the Mossbauer data show that the binding of AdoMet
      to the unique Fe site occurs in the [4Fe-4S]2+ state, prior to the injection of
      the reducing equivalent required for catalysis. This observation indicates that
      AdoMet coordination is a necessary prerequisite to adenosyl radical generation.

PMID- 11829593
TI  - First example of N-heterocyclic carbenes as catalysts for living polymerization:
      organocatalytic ring-opening polymerization of cyclic esters.
AB  - A novel metal-free, organocatalytic approach to living polymerization is
      presented. N-heterocyclic carbenes were employed as nucleophilic catalysts for
      the ring-opening polymerization (ROP) of cyclic ester monomers. The catalysts is
      used in combination with an initiator, such as an alcohol, which generates an
      alpha-end group bearing the ester from the initiating alcohol upon ring-opening
      and a hydroxyl functional omega-chain end that propagates the chain. This class
      of catalyst proved to be more reactive than tertiary amine and phosphine
      nucleophiles, producing narrowly dispersed polymers of predictable molecular
      weights at room temperature in 1-2 h. Catalysis with respect to both initiating
      alcohol and monomer was observed. Control of the alpha and omega end-groups was
      demonstrated with a pyrene-labeled initiator, allowing the preparation of well
      defined macromolecular architectures. Analogous to the ROP of cyclic esters using
      biocatalysts, the polymeriztion pathway using the N-heterocyclic carbenes is
      believed to ensue through a monomer-activated mechanism.

PMID- 11829594
TI  - Kinetic control of proline amide rotamers: total synthesis of trans,trans- and
      cis,cis-ceratospongamide.
AB  - Ceratospongamide is a cyclic peptide natural product that is biosynthesized as a
      mixture of two proline rotamers. Remarkably, these rotamers do not detectably
      interconvert at temperatures up to 100 degress C. Here we report high-yielding
      syntheses of each rotamer and demonstrate that the threonine-derived oxazoline
      plays a critical role in determining the kinetic distribution of conformational
      isomers.

PMID- 11829595
TI  - Production of meiosis-activating sterols from metabolically engineered yeast.
AB  - Meiosis-activating sterols (MAS), a class of potent regulators of reproductive
      processes, are difficult to obtain by chemical synthesis or isolation from
      natural sources. We demonstrate the development of metabolically engineered
      strains of Saccharomyces cerevisiae that accumulate MAS as the predominant sterol
      product. Homologous recombination was used to construct an erg24Delta erg25Delta
      hem1Delta mutant RXY4.3, which lacked sterol Delta14 reductase, C-4 oxidase, and
      delta-aminolevulinate synthase. The HEM1 deletion allowed sterol import and
      rendered RXY4.3 viable under aerobic conditions. This mutant accumulated 4,4
      dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol (FF-MAS), and a similar
      erg25Delta hem1Delta mutant produced 4,4-dimethyl-5alpha-cholesta-8,24-dien-3beta
      ol (T-MAS). Based on consistent yields of approximately 5 mug of FF-MAS per mL of
      culture, fermentation of genetically modified yeast compares favorably with other
      approaches to produce MAS.

PMID- 11829596
TI  - Cycloheptatrienyl oxyallyl. An observable oxyallyl?
AB  - Density functional calculations have been carried out for cycloproylidene-,
      cyclopentylidene-, and tropyllideneallene oxides (7-9) and the reaction pathway
      for their conversion to the corresponding oxyallyls (10-12) and cyclopropanones
      (13-15) in order to probe the electronic structure of the intermediate oxyallyls.
      All three oxyallyls were found to be stabilized with respect to their allene
      oxides in comparison to the unsubstituted allene oxide and oxyallyl. For 7 and 9
      the stabilization can be attributed to the zwitterionic character of the
      oxyallyls, while for 8 the stabilization can be attributed to its diradical
      character. This suggests that oxyallyl is capable of "adapting" to its local
      environment. Calculations predict that oxyallyl 12 should be an observable
      intermediate in the absence of nucleophiles, since it is calculated to be of
      lower energy than either the allene oxide 9 or the cyclopropanone 15.

PMID- 11829597
TI  - The synthesis and reactivity of a molybdenum (IV) stretched-dihydrogen complex.
AB  - Reaction of [Mo(NPh)(PMe3)3(o-(Me3SiN)2C6H4)] (1) with molecular hydrogen (ca. 1
      atm) at -10 degrees C in toluene-d8 results in the formation of dihydrogen
      complex [Mo(NPh)(PMe3)2(H2)(o-(Me3SiN)2C6H4)] (2) by 1H and 31P NMR spectroscopy.
      In solution at -50 degrees C 1 and 2 are present in a 1:3 ratio, respectively.
      The nature of dihydrogen ligand bonding in 2 was probed by T1 analysis and
      analysis of the JH-D coupling constant in the deuterium hydride isotopomer of 2
      giving H-H distances of 1.18 A and 1.17 A, respectively. When allowed to warm to
      30 degrees C, 2 reacts affording [Mo(NPh)(PMe3)3(o-(Me3SiN)(NH)C6H4)] (3) over a
      1 h period. The X-ray structures of 1 and 3 are reported.

PMID- 11829598
TI  - Synthesis of (E)-1,2-divinyl-1,2-diethynylethene (DVDEE) via the palladium
      catalyzed reaction of conjugated diynes. A new building block for molecular
      scaffolding.
AB  - Conjugated diynes undergo dimerization in the presence of acetic acid and
      catalytic amounts of Pd(PPh3)4. The unprecedented reaction gives a novel
      chromophore containing the (E)-1,2-divinyl-1.2-diethynylethene (DVDEE) module,
      which is a potentially viable building block for acetylenic scaffolding.

PMID- 11829599
TI  - CO(2) capture by a task-specific ionic liquid.
AB  - Reaction of 1-butyl imidazole with 3-bromopropylamine hydrobromide, followed by
      workup and anion exchange, yields a new room temperature ionic liquid
      incorporating a cation with an appended amine group. The new ionic liquid reacts
      reversibly with CO2, reversibly sequestering the gas as a carbamate salt. The new
      ionic liquid, which can be repeatedly recycled in this role, is comparable in
      efficiency for CO2 capture to commercial amine sequestering reagents, and yet is
      nonvolatile and does not require water to function.

PMID- 11829600
TI  - Crystal structure of double helical hexitol nucleic acids.
AB  - A huge variety of chemically modified oligonucleotide derivatives has been
      synthesized for possible antisense applications. One such derivative, hexitol
      nucleic acid (HNA), is a DNA analogue containing the standard nucleoside bases,
      but with a phosphorylated 1',5'-anhydrohexitol backbone. Hexitol nucleic acids
      are some of the strongest hybridizing antisense compounds presently known, but
      HNA duplexes are even more stable. We present here the first high-resolution
      structure of a double helical nucleic acid with all sugars being hexitols.
      Although designed to have a restricted conformational flexibility, the hexitol
      oligomer h(GTGTACAC) is able to crystallize in two different double helical
      conformations. Both structures display a high x-displacement, normal Watson-Crick
      base pairing, similar base stacking patterns, and a very deep major groove
      together with a minor groove with increased hydrophobicity. One of the
      conformations displays a major groove which is wide enough to accommodate a
      second HNA double helix resulting in the formation of a double helix of HNA
      double helices. Both structures show most similarities with the A-type helical
      structure, the anhydrohexitol chair conformation thereby acting as a good mimic
      for the furanose C3'-endo conformation observed in RNA. As compared to the quasi
      linear structure of homo-DNA, the axial position of the base in HNA allows
      efficient base stacking and hence double helix formation.

PMID- 11829602
TI  - Solubilized, spaced polyalanines: a context-free system for determining amino
      acid alpha-helix propensities.
AB  - The logical design principles behind a system of properly water-solubilized,
      spaced polyalanines are presented. Peptides conforming to these design principles
      are shown to be unaggregated, and their helical properties as measured by the
      circular dichroism (CD) residue ellipticity at 222 nm, [theta](222), are shown to
      be dependent upon the lengths of their alanine regions. It is further
      demonstrated that CD contributions of the alanine cores are independent of the CD
      contributions attributable to other features of the peptides. The CD response of
      these polyalanines to variations in temperature and salt or denaturant
      concentration is described. CD data for a series of peptides with Ala(n) cores
      varying in length from 12 to 45 residues are presented that allow calculation of
      the helical propensity, w(Ala), in a purely alanine context. Mathematical
      modeling of these unprecedented data reveals the insufficiency of currently
      accepted literature helicity modeling parameters. A modification to the standard
      Lifson-Roig algorithm is introduced based on hydrogen-bonding cooperativity.

PMID- 11829601
TI  - Consistent helicities from CD and template t/c data for N-templated polyalanines:
      progress toward resolution of the alanine helicity problem.
AB  - The helicity reporting parameters t/c and [theta](222) have been measured at 2,
      25, and 60 degrees C in water for the solubilized polyalanine series Ac-Hel-A(n)
      (t)LInp(2)K(4)W-NH(2) of length 4 < or = n < or = 14 that bears the helix
      initiating and monitoring N-cap Ac-Hel and the spaced solubilizer (t)LInp(2)K(4)W
      NH(2) as a C-cap. Correlation of t/c with length shows that the helical
      propensity for n < or = 6 is ca. 1.0, consistent with our early reports, but that
      a dramatic increase in temperature dependence and helical propensity occurs for n
      > or = 8. A model based on hydrogen-bonding cooperativity is proposed to explain
      this finding, and both t/c and [theta](222) are modeled successfully by length
      dependent alanine propensities at 2 degrees C of 1.03 for n = 6, 1.15, for 7 < or
      = n < or = 9 and 1.26 for n > or = 10. The implications of these results for the
      energetics of helix formation by alanine-rich peptide sequences are discussed.

PMID- 11829605
TI  - Copper(I)-homoscorpionate catalysts for the preferential, kinetically controlled
      cis cyclopropanation of alpha-olefins with ethyl diazoacetate.
AB  - In situ prepared copper catalysts Tp(X)Cu (Tp(X) = homoscorpionate) catalyze the
      olefin cyclopropanation reaction using ethyl diazoacetate as the carbene source.
      Very high values of both activity and diastereoselectivity toward the cis isomer
      have been obtained for styrene, alpha-methylstyrene, 1-hexene, 1-octene, vinyl
      acetate, n-butyl vinyl ether, 2,5-dimethyl-2,4-hexadiene, and 3,3-dimethyl-1
      butene. The effect of the temperature in the diastereoselectivity was almost
      negligible within the range -10 to +30 degrees C. Kinetic studies have allowed us
      to propose that the homoscorpionate ligand might act in a dihapto form during the
      catalytic process. This transformation seems to operate under kinetic control,
      where the formation of the cis isomer would govern the reaction rate.

PMID- 11829603
TI  - Fast reduction of a copper center in laccase by nitric oxide and formation of a
      peroxide intermediate.
AB  - The rapid reduction of one of the copper atoms (type 2) of tree laccase by nitric
      oxide (NO) has been detected. Addition of NO to native laccase in the presence of
      oxygen leads to EPR changes consistent with fast reduction and slow reoxidation
      of this metal center. These events are paralleled by optical changes that are
      reminiscent of formation and decay of the peroxide intermediate in a fraction of
      the enzyme population. Formation of this species is only possible if the
      trinuclear copper cluster (type 2 plus type 3) is fully reduced. This condition
      can only be met if, as suggested previously, a fraction of the enzyme contains
      both type 3 coppers already reduced before addition of NO. Our data are
      consistent with this assumption. We have suggested recently that fast reduction
      of copper is the mechanism by which NO interacts with the oxidized dinuclear
      center in cytochrome c oxidase. The present experiments using laccase strongly
      support this view and suggest this reaction as a general mechanism by which
      copper proteins interact with NO. In addition, this provides an unexploited way
      to produce a stable peroxide intermediate in copper oxidases in which the full
      complement of copper atoms is present. This enables the O-O scission step in the
      catalytic cycle to be studied by electron addition to the peroxide derivative
      through the native electron entry site, type 1 copper.

PMID- 11829604
TI  - Quantitative measurements of recombinant HIV surface glycoprotein 120 binding to
      several glycosphingolipids expressed in planar supported lipid bilayers.
AB  - The interaction of recombinant HIV-1 surface glycoprotein gp120 (rgp120) with
      natural isolates of lactosylceramide (LacCer), glucosylceramide (GlcCer), and
      galactosylceramide (GalCer) has been quantitatively measured under equilibrium
      conditions using total internal reflection fluorescence (TIRF) spectroscopy. The
      binding affinity (K(a)) of rgp120 to these glycosphingolipids (GSLs),
      reconstituted at 5 mol % in supported planar lipid bilayers composed of 95 mol %
      POPC, is ca. 10(6) M(-1) for dissolved rgp120 concentrations greater than 25 nM.
      In contrast, at concentrations of rgp120 between 0.2 and 15 nM, rgp120 does not
      bind significantly to LacCer and GlcCer, but has a high affinity for GalCer with
      a measured K(a) value of 1.6 x 10(9) M(-1). However, protein surface coverage
      measurements show that this strong binding process accounts for very little of
      the total protein adsorbed over the entire concentration range studied. At a
      protein concentration of ca. 20 nM, the surface coverage is only 3% of that
      achieved at apparent saturation (i.e., when the protein concentration is ca. 220
      nM). Thus the "high affinity" binding sites comprise only a small fraction of the
      total number of binding sites. Several other variables were investigated. Rgp120
      binding behavior at membranes doped with alpha-hydroxygalactosylceramide (alpha
      GalCer) was very similar to that observed with GalCer, showing that the
      presence/absence of an alpha-hydroxy moiety does not significantly affect
      galactosylceramide recognition. Phase segregation of GalCer, which occurs when
      the mole fraction of this GSL in a POPC bilayer exceeds ca. 0.1, was also
      investigated and showed no effect on binding affinity at low rgp120
      concentrations. To investigate the influence of fatty acid chain length, GSLs
      with monodisperse C(18) and C(24) chain lengths, both with and without an alpha
      hydroxy moiety, were synthesized, and their binding affinity to rgp120 was
      examined. Relative to the natural isolates (which contain a mixture of chain
      lengths), minimal differences were observed; thus among the compounds tested,
      fatty acid chain length does not affect GSL recognition. The results of this work
      should aid efforts to design anti-HIV-1 agents based on membrane-tethered,
      carbohydrate-based receptors for rgp120.

PMID- 11829606
TI  - The role of the achiral template in enantioselective transformations. Radical
      conjugate additions to alpha-methacrylates followed by hydrogen atom transfer.
AB  - We have evaluated various achiral templates (1a-g, 10, and 16) in conjunction
      with chiral Lewis acids in the conjugate addition of nucleophilic radicals to
      alpha-methacrylates followed by enantioselective H-atom transfer. Of these, a
      novel naphthosultam template (10) gave high enantioselectivity in the H-atom
      transfer reactions with ee's up to 90%. A chiral Lewis acid derived from MgBr(2)
      and bisoxazoline (2) gave the highest selectivity in the enantioselective
      hydrogen-atom-transfer reactions. Non-C(2) symmetric oxazolines (20-25) have also
      been examined as ligands, and of these, compound 25 gave optimal results (87%
      yield and 80% ee). Insights into rotamer control in alpha-substituted acrylates
      and the critical role of the tetrahedral sulfone moiety in realizing high
      selectivity are discussed.

PMID- 11829607
TI  - Langmuir-Blodgett films of a clay mineral and ruthenium(II) complexes with a
      noncentrosymmetric structure.
AB  - Mono- and multilayers of amphiphilic [Ru(phen)(2)(dcC12bpy)](2+) (phen = 1,10
      phenanthroline, dcC12bpy = 4,4'-caboxyl-2,2'-bipyridyl didodecyl ester)
      hybridized with a clay mineral have been prepared by a modified Langmuir-Blodgett
      method, and their structures and properties have been investigated. Formation of
      a hybrid monolayer of the Ru(II) complex cations and the clay platelets at an air
      clay suspension interface was confirmed by surface pressure-molecular area (pi-A)
      isotherm measurement and atomic force microscopic (AFM) observation. Multilayers
      were fabricated by depositing the hybrid monolayers onto glass substrates. The
      absorbance at 492 nm due to the Ru(II) complex cation in the multilayer increased
      linearly with the increase in the layer number, indicating layer-by-layer
      deposition of the hybrid monolayers. Because no increase in the second-harmonic
      generation (SHG) signal from the multilayers against the layer number was
      observed, the orientation of the Ru(II) complex cations in the layer would be
      disturbed. The hydrophilic surface of the transferred hybrid monolayer can be
      converted to a hydrophobic surface by dipping it in an aqueous solution of
      octadecylammonium chloride (ODAH(+)Cl(-)). The multilayers modified with ODAH(+)
      showed a quadratic relation between the SHG intensity and the layer number. This
      means that the Ru(II) complex cations in the multilayer are successfully oriented
      in a noncentrosymmetric way by the conversion of the surface property. Both a
      racemic mixture and an enantiomer of the Ru(II) complex cations were employed to
      examine the chiral effect on the film properties. The chiral contribution to the
      SHG signal was enhanced in the multilayer modified with ODAH(+).

PMID- 11829608
TI  - Oxo-transfer reaction from a bis(mu-oxo)dicopper(III) complex to sulfides.
AB  - Oxygenation of sulfides to the corresponding sulfoxides by a distinct bis(mu
      oxo)dicopper(III) complex has been accomplished for the first time using 2-(2
      pyridyl)ethylamine derivative L(Py1Bz) (N-ethyl-N-[2-(2-pyridyl)ethyl]
      alpha,alpha-dideuteriobenzylamine) as the supporting ligand. Detailed kinetic
      analysis has indicated that the reaction consists of two distinct steps, where
      the first quick process is association of the substrate to the bis(mu
      oxo)dicopper(III) complex (k(1)) and the second slow process is intramolecular
      oxygen atom transfer from the copper-oxo species to the substrate in the
      associated complex (k(2)). The rate constant k(2) of the second process is rather
      insensitive to the oxidation potential of the substrates, suggesting that the oxo
      transfer reaction proceeds via a mechanism involving direct oxygen atom transfer
      rather than a mechanism involving electron transfer.

PMID- 11829609
TI  - Metallacycles of porphyrins as building blocks in the construction of higher
      order assemblies through axial coordination of bridging ligands: solution- and
      solid-state characterization of molecular sandwiches and molecular wires.
AB  - Treatment of the octahedral Ru(II)-dimethyl sulfoxide complexes trans
      RuCl(2)(dmso-S)(4) (1), trans-RuCl(2)(dmso-O)(2)(CO)(2) (2), and trans
      RuCl(2)(dmso)(3)(CO) (3) with a stoichiometric amount of 5,10-bis(4'-pyridyl)
      15,20-diphenylporphyrin (4'-cis-DPyP) yields, after chromatographic purification,
      the novel 2+2 molecular squares of formula [trans,cis,cis-RuCl(2)(dmso-S)(2)(4'
      cis-DPyP)](2) (4), [trans,cis,cis-RuCl(2)(CO)(2)(4'-cis-DPyP)](2) (5), and
      [trans,cis,cis-RuCl(2)(dmso-S)(CO)(4'-cis-DPyP)](2) (6), respectively. Compound 6
      exists as an equimolar mixture of the isomeric metallacycles 6a and 6b, depending
      on whether the 4'-N(py) rings of 4'-cis-DPyP's are trans to CO or to dmso-S.
      Compounds 4-6 were fully characterized by NMR and IR spectroscopy and by FAB mass
      spectrometry. Treatment of 5 with excess zinc acetate in chloroform/methanol
      mixtures led to the isolation of the corresponding zinc adduct [trans,cis,cis
      RuCl(2)(CO)(2)(Zn x 4'-cis-DPyP)](2) (5Zn). Treatment of 5Zn with 1 equiv of a
      trans ditopic N-donor ligand L (L = 4,4'-bipy, 5,15-bis(4'-pyridyl)-2,8,12,18
      tetra-n-propyl-3,7,13,17-tetramethylporphyrin (4'-trans-DPyP-npm), or 5,15-bis(4'
      pyridyl)-10,20-diphenylporphyrin (4'-trans-DPyP)) leads readily and selectively,
      according to (1)H NMR spectroscopy, to the quantitative assembling of 2:2
      supramolecular adducts of stacked metallacycles of formula [(5Zn)(2)(mu-L)(2)] (7
      9), which were thoroughly characterized in solution by NMR spectroscopy. NMR
      features indicate that, at ambient temperature, the equilibrium between 5Zn and L
      to yield [(5Zn)(2)(mu-L)(2)] has an intermediate to slow rate on the NMR time
      scale (relatively broad signals for L) and is totally shifted toward the 2:2
      product (all or nothing process). Single-crystal X-ray investigations showed
      that, depending on the nature of the bridging ligand, in the solid state these
      sandwich structures can either be maintained or originate polymeric chains
      formulated as [(5Zn)(mu-L)](infinity). When L = 4'-trans-DPyP, both solution- and
      solid-state data indicate that [(5Zn)(2)(mu-4'-trans-DPyP)(2)] (9) is a discrete
      supramolecular assembly of two molecular squares of metalloporphyrins axially
      connected through other porphyrins. In this molecular box, the two bridging
      porphyrins are coplanar at a distance of about 11.4 A. When L = 4,4'-bipy, the
      corresponding adduct 7 has the anticipated sandwich-like discrete architecture
      [(5Zn)(2)(mu-4,4'-bipy)(2)] in solution, but it assumes a stair-like polymeric
      wire structure in the solid state. The polymer [(5Zn)(mu-4,4'-bipy)](infinity) is
      made by 5Zn squares bridged by 4,4'-bipy ligands which are axially coordinated
      alternatively on the two opposite sides of each square. Our work clearly
      established that relatively simple supramolecular adducts of porphyrins, such as
      molecular squares, are suitable building blocks for the construction of more
      elaborate assemblies of higher order by axial coordination of bridging ligands.

PMID- 11829610
TI  - Rhodium chemzymes: Michaelis-Menten kinetics in dirhodium(II) carboxylate
      catalyzed carbenoid reactions.
AB  - Rhodium carboxylate-mediated reactions of diazoketones involving
      cyclopropanation, C-H insertion, and aromatic C-C double bond
      addition/electrocyclic ring opening obey saturation (Michaelis-Menten) kinetics.
      Axial ligands for rhodium, including aromatic hydrocarbons and Lewis bases such
      as nitriles, ethers, and ketones, inhibit these reactions by a mixed kinetic
      inhibition mechanism, meaning that they can bind both to the free catalyst and to
      the catalyst-substrate complex. Substrate inhibition can also be exhibited by
      diazocompounds bearing these groupings in addition to the diazo group. The
      analysis of inhibition shows that the active catalyst uses only one of its two
      coordination sites at a time for catalysis. Some ketones exhibit the interesting
      property that they selectively bind to the catalyst-substrate complex. The
      similarity of the kinetic constants from different types of reactions with
      similar diazoketones, regardless of the linking unit or the environment of the
      reacting alkene, suggests that the rate-determining step is the generation of the
      rhodium carbenoid. A very useful rhodium carboxylate catalyst for asymmetric
      synthesis, Rh(2)(DOSP)(4), shows slightly slower kinetic parameters than the
      achiral catalysts, implying that enantioselectivity of this catalyst is based on
      slowing reactions from one of the enantiotopic faces of the reactant, rather than
      any type of ligand-accelerated catalysis. A series of rhodium catalysts derived
      from acids with pK(a)s spanning 4 orders of magnitude give very similar kinetic
      constants.

PMID- 11829611
TI  - Synthesis and spectroscopic properties of elongated ruthenium dihydrogen
      complexes: temperature and isotope dependence of H-H distances.
AB  - Several dihydrogen complexes of ruthenium of the form [Cp/Cp*Ru(P-P)H(2)](+) (P-P
      = chelating diphosphine ligand) have been prepared by reaction of the
      corresponding neutral chloride complexes with H(2) in the presence of
      NaB(ArF)(4). Treatment with D(2) or T(2) gas leads to incorporation of deuterium
      or tritium in the dihydrogen ligand. Measurement of the resulting H-D and H-T
      couplings as a function of the temperature and magnetic field gives results
      consistent with computational studies which predict that the H-H bond distance
      will increase with temperature and will be significantly shortened by isotopic
      substitution. The degree of the observed temperature dependence is found to be a
      critical function of the ancillary ligand set.

PMID- 11829612
TI  - Synthesis and characterization of Pt(CN-p-(C(2)H(5))C(6)H(4))(2)(CN)(2), a
      crystalline vapoluminescent compound that detects vapor-phase aromatic
      hydrocarbons.
AB  - The vapochromic and vapoluminescent compound Pt(CN-p
      (C(2)H(5))C(6)H(4))(2)(CN)(2) (abbreviated PtC(2)) is conveniently synthesized by
      the thermal rearrangement of [Pt(CN-p-(C(2)H(5))C(6)H(4))(4)][Pt(CN)(4)].
      Recrystallization of PtC(2) gives a crystalline orange morph (O-PtC(2)) and an
      amorphous purple morph (P-PtC(2)) that both contain the cis isomer and differ
      only in their solid-state packing arrangements. Both compounds were fully
      characterized by elemental analysis, X-ray powder diffraction, NMR, IR, and TGA.
      O-PtC(2) is vapochromic and vapoluminescent: it reversibly sorbs aromatic
      hydrocarbons and ethanol from air or nitrogen with resulting color changes and
      shifts in the emission spectrum. The lambda(max) values (nm) for emission from O
      PtC(2) x (guest) are as follows: no guest, 611; toluene, 565; benzene, 586;
      chlorobenzene, 592; p-xylene, 585; mesitylene, 565; ethanol, 587. In the case of
      toluene and mesitylene, intermediate emitting phases are observed.
      Recrystallization of O-PtC(2) from dichloromethane/toluene gave single crystals
      of PtC(2) x 0.5(toluene). The single-crystal X-ray structure of PtC(2) x
      0.5(toluene) contains infinite stacks of cis geometry and planar molecules with
      chains of platinum atoms parallel to the c axis of the monoclinic unit cell. The
      average Pt-Pt separation in PtC(2) x 0.5(toluene) is c/4 = 3.288(2) A. There are
      solvent channels parallel with the c axis that contain the toluene molecule
      guests. Thin films of O-PtC(2) rapidly sorb toluene from the gas phase to form
      PtC(2) x 0.25(toluene) and PtC(2) x 0.5(toluene). Long-term exposure gives PtC(2)
      x 1.0(toluene). Removal of the toluene source causes rapid desorption to PtC(2) x
      0.5(toluene) and then to PtC(2) x 0.25(toluene). The remaining 0.25(toluene)
      lattice guests require heating for rapid removal. X-ray powder diffraction
      identified the PtC(2),PtC(2) x .25(toluene), and PtC(2) x 0.5(toluene) phases and
      showed that the sorption of toluene is accompanied by small changes in the unit
      cell dimensions that include lengthening the Pt-Pt distances in the structure.
      The sorption process improves the packing in the structure by utilizing some of
      the free volume for the toluene lattice guests.

PMID- 11829613
TI  - Framework stability of nanoporous inorganic structures upon template extraction
      and calcination: a theoretical study of gallophosphate polymorphs.
AB  - A systematic computational study of gallophosphates was undertaken. First,
      lattice energy minimization calculations using a formal-charge shell model
      potential have been carried out on a series of hypothetical gallium phosphates
      derived from their metallogallophosphate, aluminophosphate, or aluminosilicate
      analogues through atomic substitution. The minimized structures show the typical
      features in terms of bond angles and distances as expected in zeolitic
      gallophosphates. Second, the crystal structures of several gallophosphates in
      their calcined forms have been predicted, using for each compound lattice energy
      minimization and an initial model derived from its as-synthesized templated form.
      All the modified structures thus have the same GaPO(4) composition. The lattice
      energies of all the simulated gallophosphate structures were compared to that of
      GaPO(4)-quartz as a reference structure. Interestingly, among all predicted
      calcined structures, various zeolitic topologies were found. The study of the
      energetics of these zeotypic structures showed a linear dependence of lattice
      energy upon density. Strikingly, a few simulated structures showed unrealistic
      structural features, such as important framework distortions, often associated
      with the occurrence of a hexameric unit in the original as-synthesized
      structures. Also, those gallophosphates with structural faults were found in the
      upper part of the energy/density plot. To address the validity of our force field
      calculations in these special cases, first principles calculations were
      undertaken on ULM-4, chosen as a typical representative structure. Indeed, the
      qualitative agreement found between our results and those obtained with the
      nonlocal density functional theory demonstrates the robustness of our force
      field. Further minimization also showed that the inclusion of polarizability is
      crucial for yielding results comparable with those obtained using first
      principles methods.

PMID- 11829614
TI  - Synthesis of zigzag-chain and cyclic-octanuclear calcium complexes and
      hexanuclear bulky aryl-phosphate sodium complexes with ortho-amide groups:
      structural transformation involving a network of inter- and intramolecular
      hydrogen bonds.
AB  - Three new polynuclear Ca(II)- and Na(I) phosphate complexes with two
      strategically oriented bulky amide groups, 2,6-(PhCONH)(2)C(6)H(3)OPO(3)H(2),
      were synthesized, including one with a zigzag-chain, [Ca(II)[O(3)POC(6)H(3)-2,6
      (NHCOPh)(2)](H(2)O)(4)(EtOH)](n), a cyclic-octanuclear form,
      [Ca(II)(8)[O(3)POC(6)H(3)-2,6-(NHCOPh)(2)](8)(O=CHNMe(2))(8)(H(2)O)(12)], and a
      hexanuclear complex, (NHEt(3))[Na(3)[O(3)POC(6)H(3)-2,6
      (NHCOPh)(2)](2)(H(2)O)(MeOH)(7)]. X-ray crystallography revealed that all have an
      unsymmetric ligand position due to the bulky amide groups. A dynamic
      transformation of the Ca(II) zigzag-chain structure to the cyclic-octanuclear
      complex was induced by changing coordination of DMF molecules, which caused a
      reorganization of the intermolecular/intramolecular hydrogen bond network.

PMID- 11829615
TI  - Mechanism of the palladium-catalyzed metal-carbon bond formation. A dual pathway
      for the transmetalation step.
AB  - The mechanism of the transmetalation step in the metal-carbon bond-formation
      process catalyzed by palladium complexes has been studied by spectroscopic and
      kinetic methods. The reaction of properly designed model complexes [structure:
      see text], resulting from oxidative addition of a Mo-I moiety to a palladium
      center, with aryltributyltinacetylides Bu(3)Sn-C [triple bond] C-(p-XC(6)H(4))
      (11a, X = H; 11b, X = Cl) yields the products of transmetalation [structure: see
      text] (5a,b). The reaction, which shows a strong dependence on the nature of the
      phosphine ligand PR(3) (Ph > Bu > Me) and less so on the nature of the p
      substituent X group, proceeds through two competing pathways, depending on the
      initial concentration of substrate. At high [3] (approximately equal to 10(-2)
      M), the transmetalation proceeds through an intermediate species (12) formed by
      the interaction of complex 3 with 11a. This associative complex accumulates in
      the presence of added PPh(3) and has been characterized spectroscopically. At low
      [3] (approximately equal to 10(-4) M), the reaction rate shows an inverse
      dependence on the concentration of the complex. This is due to the formation of a
      solvent-coordinate species (13), in which PPh(3) has been substituted by a
      dimethylformamide (DMF) molecule, as shown by UV-vis and (31)P NMR spectroscopy.
      Values of k(obs) depend on the concentration and nature of the
      aryltributyltinacetylides, in agreement with the existence of a kinetically
      detectable intermediate. A dimeric iodide bridged complex [structure: see
      text](14) has been obtained during attempts at isolating 13, which changes
      quantitatively into 13 upon dissolution in DMF and reacts with 11a to give the
      transmetalation product.

PMID- 11829616
TI  - Selective detection and assignment of the solution NMR signals of
      bacteriochlorophyll a in a reconstituted subunit of a light-harvesting complex.
AB  - High-resolution solution NMR spectra have been obtained for bacteriochlorophyll
      (BChl) a molecules in a biologically functional subunit of a bacterial core light
      harvesting complex based on a modified reconstitution method. The reconstituted
      subunit of pigment-integral membrane polypeptides is stable and homogeneous at
      high concentrations at room temperature and exhibits a Q(y) absorption peak at
      818 nm. (1)H and (13)C chemical shifts have been specifically assigned for BChl a
      using the fully and selectively (13)C-labeled pigments incorporated with natural
      abundance polypeptides in deuterated detergent solution. Remarkable signal
      broadening has been observed upon reconstitution, where the bacteriochlorin
      macrocycle is shown in a highly restricted molecular motion while the phytol side
      chain remains relatively mobile. Two sets of resonances are revealed for 3(2),
      8(1), 10, 12(1), and 13(4) protons, and 8(2) methyl protons exhibit four
      resonances with large upfield complexation shifts. The result indicates a
      nonequivalent state for the two BChl a molecules in the subunit and can be best
      interpreted in terms of a parallel face-to-face configuration with partial
      overlap over the pyrrolic rings II, III, and V. In comparison with BChl a in
      acetone, 8(2), 13(2), and 13(4) protons are largely perturbed, and the propionic
      and phytol side chain may adopt a different conformation in the reconstituted
      subunit. The (13)C chemical shift of 3(1) carbonyl carbon shows a large change
      downfield, indicating strong hydrogen bonding for all the acetyl carbonyls.
      Carbonyl carbons at 13(1) give rise to two (13)C resonances with equal
      intensities, suggesting that the keto carbonyl in one BChl a molecule within a
      subunit forms a stronger hydrogen bond than that in another BChl a molecule.

PMID- 11829617
TI  - Nd-Fe-B permanent magnet electrodes. Theoretical evaluation and experimental
      demonstration of the paramagnetic body forces.
AB  - Cyclic voltammetry with Nd-Fe-B disk magnet electrodes (3.2 mm diameter) at slow
      sweep rates (< or = 0.01 V s(-1)) in relatively concentrated solutions (e.g., 80
      mM) of diamagnetic redox-active species (e.g., TMPD) is controlled by diffusion.
      Under similar conditions, cyclic voltammetry with conventional noble metal disk
      millielectrodes is characterized by the absence of diffusion waves and the
      presence of density gradient driven natural convection. Although the magnetic
      field in the vicinity of Nd-Fe-B electrodes is relatively strong (approximately
      0.5 T at the surface of the magnet electrode), the absence of magnetohydrodynamic
      stirring effects is attributed to the fact that the i and B vectors are almost
      parallel, and therefore the magnetohydrodynamic force F(B) (=i x B) is very
      small. On the other hand, the absence of natural convection is attributed to the
      two possible paramagnetic body forces, F(inverted Delta B) and F(inverted Delta
      C), exerted by the magnet electrode on the diffusion layer. Of those two forces,
      the former depends on field gradients (F(inverted Delta B) approximately B x
      inverted Delta B), while the latter depends on concentration gradients
      (F(inverted Delta C) approximately inverted Delta C(j)) and is directed toward
      areas with higher concentration of paramagnetic j. Through thorough analysis of
      the magnetic field and its gradients, it is found that the average F(inverted
      Delta C) force acting upon the entire diffusion layer is approximately 1.75 times
      stronger than F(inverted Delta B). Nevertheless, it is calculated that either
      force independently is strong enough and would have been able to hold the
      diffusion layer by itself. Further evidence suggests that, integrated over the
      entire solution, F(inverted Delta B) is the dominant paramagnetic force when the
      redox-active species is paramagnetic, e.g., [Co(bipy)(3)](ClO(4))(2) (bipy = 2,2'
      bipyridine). Finally, convective behavior with diamagnetic redox-active species
      and magnet millielectrodes can be observed by holding closely (2-3 mm away) a
      repelling second magnet that bends the induction B to the point that the i x B
      product is not equal to 0. with Nd-Fe-B disk ma

PMID- 11829618
TI  - Electronic determinants of photoacidity in cyanonaphthols.
AB  - We present semiempirical AM1 calculations for the ground and excited state of 2
      naphthol and some of its cyano derivatives in the gas phase. Following
      photoexcitation, the Mulliken electron density on the oxygen diminishes slightly
      for the acid and more conspicuously for the anionic conjugated base. This agrees
      with the measured solvatochromic parameters for 2-naphthol. In both electronic
      states, we find a nice correlation with the measured pK values in water. The
      electronic charge distribution on the distal ring of the anion agrees with the
      experimental acidity order in both S(0) and S(1). Upon excitation, it increases
      predominantly in positions 3, 5, and 8. The ring system of the anion assumes an
      alternate quinoidal structure in the ground state of the anion, which becomes
      more symmetric in the relaxed excited state. This suggests that the enhanced
      aromatic character of a 4n electron system in the excited state allows for better
      delocalization of the oxygen charge within the ring.

PMID- 11829620
TI  - Solid-state reaction study of the trans-to-cis isomerization of (eta
      C(5)H(4)Me)Re(CO)[P(OPh)(3)]Br(2): a new mechanism for the isomerization
      reaction.
AB  - Single-crystal X-ray structures have been determined at intermediate stages in
      the single-crystal to single-crystal trans-to-cis thermal isomerization of
      (eta(5)-C(5)H(4)Me)Re(CO)[P(OPh)(3)]Br(2) at 150 degrees C. Unit cell parameters
      and site occupancy factors linked to the induced disorder were monitored and
      found to follow first-order kinetics in the initial (fast component) stage of the
      reaction. A rate constant of 30 x 10(-6) s(-1) (0.11 h(-1)) was obtained to first
      order approximation for the reaction. The irreversibility of the isomerization
      from single crystals of the cis form was also confirmed. Fourier and difference
      Fourier maps suggest a novel 2-fold rotation mechanism for the trans-to-cis
      isomerization reaction. This mechanism entails a unidirectional anticlockwise
      movement of the CO ligand and only one Br atom.

PMID- 11829619
TI  - Hybridization of DNA and PNA molecular beacons to single-stranded and double
      stranded DNA targets.
AB  - Molecular beacons are sensitive fluorescent probes hybridizing selectively to
      designated DNA and RNA targets. They have recently become practical tools for
      quantitative real-time monitoring of single-stranded nucleic acids. Here, we
      comparatively study the performance of a variety of such probes, stemless and
      stem-containing DNA and PNA (peptide nucleic acid) beacons, in Tris-buffer
      solutions containing various concentrations of NaCl and MgCl(2). We demonstrate
      that different molecular beacons respond differently to the change of salt
      concentration, which could be attributed to the differences in their backbones
      and constructions. We have found that the stemless PNA beacon hybridizes rapidly
      to the complementary oligodeoxynucleotide and is less sensitive than the DNA
      beacons to the change of salt thus allowing effective detection of nucleic acid
      targets under various conditions. Though we found stemless DNA beacons improper
      for diagnostic purposes due to high background fluorescence, we believe that use
      of these DNA and similar RNA constructs in molecular-biophysical studies may be
      helpful for analysis of conformational flexibility of single-stranded nucleic
      acids. With the aid of PNA "openers", molecular beacons were employed for the
      detection of a chosen target sequence directly in double-stranded DNA (dsDNA).
      Conditions are found where the stemless PNA beacon strongly discriminates the
      complementary versus mismatched dsDNA targets. Together with the insensitivity of
      PNA beacons to the presence of salt and DNA-binding/processing proteins, the
      latter results demonstrate the potential of these probes as robust tools for
      recognition of specific sequences within dsDNA without denaturation and
      deproteinization of duplex DNA.

PMID- 11829621
TI  - Generalized correlation NMR spectroscopy.
AB  - The use of generalized correlation analysis (Noda, I. Appl. Spectrosc. 1993, 47,
      1329-1336) for processing two-dimensional arrays of NMR data is described. This
      analysis produces complex two-dimensional spectra whose cross-peak intensities
      are related to correlations in the responses of pairs of signals to
      systematically incremented perturbations. The technique extends and generalizes
      the applicability of two-dimensional NMR by allowing model-independent analysis
      of nonperiodic signals as well as model-dependent analysis of such signals. When
      applied to diffusion-ordered NMR data, the processing scheme produces two
      dimensional output spectra having two frequency axes. Relative diffusion
      coefficients are encoded in the signs and intensities of the cross-peaks. Key
      properties of the resulting spectra are model-independent, so the approach
      provides an alternative to traditional DOSY processing and offers advantages for
      data sets that do not provide pure exponential or Gaussian response curves. When
      data do conform well to a known response function, the technique provides a
      method for extracting descriptors in a two-dimensional plot having one axis
      corresponding to the descriptor and the other axis corresponding to the usual
      chemical shift scale. Finally, the technique may be used to identify differences
      in the response functions of closely related samples, generating a one
      dimensional spectrum with signals at frequencies whose response functions differ
      between two samples.

PMID- 11829622
TI  - A fresh look at aromatic dianions.
AB  - Isolated dianions of cyclooctatetraene and cyclobutadiene are, despite their
      aromatic character, unstable with respect to electron loss. Here we present the
      first ab initio study of the autodetachment lifetimes of several "aromatic"
      dianions. In particular, we investigate whether aromatic pi systems are
      associated with an enhanced stability with respect to electron loss and whether
      cross-conjugated (Y-aromatic) hydrocarbon dianions possess longer lifetimes than
      their linear-conjugated isomers. Moreover, our results are compared with bound
      state calculations for these metastable dianions, allowing us to analyze the
      validity of the latter approach. All considered, hydrocarbon dianions are found
      to possess surprisingly short autodetachment lifetimes on the order of a few
      femtoseconds, and therefore only electron scattering techniques seem to be
      capable of observing these species in the gas phase. The trends of the computed
      energies and lifetimes are best understood in terms of the mutual Coulomb
      repulsion of the extra charges. Small gas phase dianions can only be stable if
      the excess electrons can localize at least at two subgroups of high local
      electron affinity. Adding both extra electrons into one delocalized pi system
      leads to a very unstable species, and thus especially those structures associated
      with pronounced aromaticity are found to show high energies and short lifetimes.

PMID- 11829624
TI  - Optimization of solid-phase microextraction analysis for studying change of
      headspace flavor compounds of banana during ripening.
AB  - The changes of headspace flavor compounds of banana during ripening were studied
      by a solid-phase microextraction (SPME) method. Three temperatures, 20, 25, and
      30 degrees C, were used to investigate the temperature effect on the changes of
      headspace flavor compounds of banana during ripening over a period of 8 days.
      Banana juice concentration, salt concentration, time, and temperature were
      investigated for optimizing the SPME method. The most suitable concentrations of
      banana juice and salt were 33.3 and 20%, respectively. The optimal temperature
      and time are about 50 degrees C and 48 min, respectively. Increasing ripening
      temperature could accelerate ripening rate. Ethanol developed most rapidly at 30
      degrees C, whereas amounts of the other investigated flavor compounds stored at
      25 degrees C were greater than those of the ones stored at 20 or 30 degrees C.

PMID- 11829625
TI  - Abundance and reactivity of dibenzodioxocins in softwood lignin.
AB  - To define the abundance and comprehend the reactivity of dibenzodioxocins in
      lignin, model compound studies, specific degradation experiments on milled wood
      lignin, and molecular modeling calculations have been performed. Quantitative
      (31)P NMR measurements of the increase of biphenolic hydroxyl groups formed after
      a series of alkaline degradations in the presence of hydrosulfide anions (kraft
      conditions) showed the presence of 3.7 dibenzodioxocin rings/100 C9 units in
      milled wood lignin. The DFRC degradation protocol (Derivatization Followed by
      Reductive Cleavage) was chosen as an independent means to estimate their
      abundance. Initial experiments with a dibenzodioxocin model compound, trans-6,7
      dihydro-7-(4-hydroxy-3-methoxyphenyl)-4,9-dimethoxy-2,11
      dipropyldibenzo[e,g][1,4]dioxocin-6-ylmethanol, showed that it is not cleaved
      under DFRC conditions, but rather it isomerizes into a cyclic oxepine structure.
      Steric effects precluded this isomerization from occurring when DFRC was applied
      to milled wood lignin. Instead, monoacetylated biphenolic moieties were released
      and quantified by (31)P NMR, at 4.3 dibenzodioxocin rings/100 C9 units. The
      dibenzodioxocin content in residual lignins isolated from kraft pulps delignified
      to various degrees showed that during pulp delignification, the initial rate of
      dibenzodioxocin removal was considerably greater than the cleavage rate of
      arylglycerol-beta-aryl ether bonds. The activation energy for the degradation of
      dibenzodioxocins under kraft conditions in milled wood lignin was 96 +/- 9
      kJ/mol, similar to that of arylglycerol-beta-aryl ether bond cleavage.

PMID- 11829626
TI  - Barley viability during storage: use of magnetic resonance as a potential tool to
      study viability loss.
AB  - Malting-quality barley samples of the varieties Harrington, Manley, and TR118,
      each from two locations in Saskatchewan, were collected directly from the
      producers and sent to China for storage. At regular intervals samples were
      shipped back to Canada for analysis consisting of germination studies, alpha
      amylase tests, magnetic resonance imaging (MRI), and magnetic relaxation (NMR)
      studies. Samples showing a decrease in germinative energy and elevated levels of
      alpha-amylase also showed a rapid uptake of water in the area between the embryo
      and the endosperm as observed by MRI. Using NMR relaxation experiments, viable
      and nonviable barley samples could be distinguished after 2 h of imbibition.

PMID- 11829627
TI  - Novel polyphenol molecule isolated from licorice root (Glycrrhiza glabra) induces
      apoptosis, G2/M cell cycle arrest, and Bcl-2 phosphorylation in tumor cell lines.
AB  - Herbal therapies are commonly used by patients with cancer, despite little
      understanding about biologically active chemical derivatives. We recently
      demonstrated that the herbal combination PC-SPES, which contains licorice root,
      had anti-prostate cancer activity attributable to estrogen(s) that produced a
      chemical castration. A recent study also demonstrated that licorice root alone
      decreased circulating testosterone in men. Other studies demonstrated antitumor
      activity of PC-SPES in vitro associated with decreased expression of the anti
      apoptotic protein Bcl-2 and in patients independent of chemical castration,
      suggesting that other mechanisms of antitumor activity exist separate from
      chemical castration. In the present study, we assessed licorice root extract for
      effects on Bcl-2 to identify novel cytotoxic derivatives. Licorice root extract
      induced Bcl-2 phosphorylation as demonstrated by immunoblot and G2/M cell cycle
      arrest, similarly to clinically used antimicrotubule agents such as paclitaxel.
      Bioassay-directed fractionations resulted in a biologically active fraction for
      Bcl-2 phosphorylation. HPLC separation followed by mass spectrometry and NMR
      identified 6 compounds. Only one molecule was responsible for Bcl-2
      phosphorylation; it was identified as 1-(2,4-dihydroxyphenyl)-3-hydroxy-3-(4'
      hydroxyphenyl) 1-propanone (beta-hydroxy-DHP). The effect on Bcl-2 was structure
      specific, because alpha-hydroxy-DHP, 1-(2,4-dihydroxyphenyl)-2-hydroxy-3-(4'
      hydroxyphenyl) 1-propanone, in contrast to beta-hydroxy-DHP, was not capable of
      Bcl-2 phosphorylation. Pure beta-hydroxy-DHP induced Bcl-2 phosphorylation in
      breast and prostate tumor cells, G2/M cell cycle arrest, apoptosis demonstrated
      by Annexin V and TUNEL assay, decreased cell viability demonstrated by a
      tetrazolium (MTT) assay, and altered microtubule structure. Therefore, these data
      demonstrate that licorice root contains beta-hydroxy-DHP, which induced Bcl-2
      phosphorylation, apoptosis, and G2/M cell cycle arrest, in breast and prostate
      tumor cells, similarly to the action of more complex (MW >800) antimicrotubule
      agents used clinically.

PMID- 11829628
TI  - Extraction of natural vitamin E from wheat germ by supercritical carbon dioxide.
AB  - An efficient supercritical fluid extraction (SFE) process with carbon dioxide
      (SFE-CO(2)) was developed for the extraction of natural vitamin E (V(E)) from
      wheat germ. Both the pretreatment of extracted wheat germ and extraction
      conditions were optimized to ensure maximal V(E) yield. The extraction was
      undertaken at the extracting pressure of 4000-5000 psi, the extracting
      temperature of 40-45 degrees C, and the carbon dioxide flow rate of 2.0 mL/min
      for 90 min. An optimized pretreatment of wheat germ was usually necessary with a
      particle size of 30 mesh and a moisture content of 5.1%. A yield comparison of
      V(E) and its isomers extracted by supercritical CO(2) with those by conventional
      solvent extraction suggested that this SFE process was a practical process
      prospectively superior to conventional solvent extraction to prepare V(E) from
      wheat germ.

PMID- 11829629
TI  - Effects of intact glucosinolates and products produced from glucosinolates in
      myrosinase-catalyzed hydrolysis on the potato cyst nematode (Globodera
      rostochiensis Cv. Woll).
AB  - The potato cyst nematode (Globodera rostochiensis cv. Woll) is responsible for
      large yield losses in the potato crop, and opportunities for reducing the attack
      of these plant nematode species are, therefore, important. This study has been
      devoted to the testing of the in vitro effects on the potato cyst nematode of
      eight glucosinolates [prop-2-enyl-, but-3-enyl-, (R)-4-methylsulfinylbut-3-enyl-,
      benzyl-, phenethyl-, 4-hydroxybenzyl-, (2S)-2-hydroxybut-3-enyl-, and (2R)-2
      hydroxy-2-phenylethylglucosinolate] as well as the effects of the products of
      this myrosinase-catalyzed hydrolysis. The glucosinolates were used at three
      concentrations, 0.05, 0.3, and 1.0 mg/mL, in the presence or absence of the
      enzyme myrosinase. The effects of the compounds on the mortality were monitored
      every 8 h for a 72 h period. No effects were found for any of the intact
      glucosinolates. However, when active myrosinase was included with 1 mg/mL
      phenethylglucosinolate at pH 6.5, 100% mortality was observed within just 16 h. A
      similar effect was achieved at the same concentration of benzyl- and prop-2
      enylglucosinolates in the myrosinase-containing solutions, although longer
      exposures were required (24 and 40 h, respectively). The main aglucone products
      released from the glucosinolates with pronounced effects on the nematodes were
      shown to be the corresponding isothiocyanates. The results suggest that mixtures
      of these specific glucosinolates and active myrosinase or autolysis of plant
      materials containing these enzymes and glucosinolates might be used to control
      the potato cyst nematode in the soil.

PMID- 11829630
TI  - Isolation and characterization of a bioactive mannose-binding protein from the
      Chinese chive Allium tuberosum.
AB  - A mannose-binding protein was isolated from two different cultivars of the
      Chinese chive Allium tuberosum by extraction with 0.2 M NaCl, ammonium sulfate
      precipitation, and affinity chromatography on mannose agarose and fetuin agarose.
      It exhibited hemagglutinating activity toward rabbit erythrocytes. The lectin
      (agglutinin) was adsorbed on the mannose-agarose column, but not on the fetuin
      agarose column. This A. tuberosum lectin (ATL) is unglycosylated, and not sialic
      acid binding. Lectins isolated from the two cultivars exhibited the same
      molecular mass of 25 kDa on gel filtration (Superose 12) and 12.5 kDa on SDS
      polyacrylamide gel electrophoresis, indicating that they might be a dimeric
      protein composed of two identical subunits. The N-terminal amino acid sequence
      analysis of the lectin of various cultivars of A. tuberosum revealed that they
      were identical and showed 50%, or more, homology to the lectins from Galanthus
      nivalis (family Amaryllidaceae), Narcissus tazetta (family Amaryllidaceae), and
      Aloe arborescenes (family Liliaceae).

PMID- 11829632
TI  - Evaluation of peracid formation as the basis for resistance to infection in
      plants transformed with haloperoxidase.
AB  - Nonheme haloperoxidase (HPO-P) isolated from Pseudomonas pyrrocinia catalyzed the
      peroxidation of alkyl acids to peracids. Among acids tested as substrates, acetic
      acid was most readily peroxidized. The reaction product peracetate possessed
      potent antifungal activity: 50% death (LD(50)) of Aspergillus flavus occurred at
      25 microM peracetate. Viability of A. flavus was inhibited by up to 80% by leaf
      extracts of tobacco plants transformed with the HPO-P gene from P. pyrrocinia
      compared to viability of fungi exposed to extracts from controls. To elucidate if
      peracid formation by HPO-P was the basis for antifungal activity in transgenic
      leaf tissues, lethalities of hydrogen peroxide-acetate-HPO-P combinations against
      A. flavus were examined in vitro. LD(50) of A. flavus exposed to the combinations
      occurred at 30 mM acetate when concentrations of hydrogen peroxide and HPO-P were
      held constant. This value was identical to the LD(50) produced by 30 mM acetate
      in the absence of hydrogen peroxide-HPO-P and therefore did not account for
      enhanced antifungal activity in transgenic plants. For clarification, kinetics of
      the enzymic reaction were examined. According to the concentration of acetate
      needed for enzyme saturation (K(m) = 250 mM), acetate was lethal prior to its
      oxidation to peracetate. Results indicate that peracid generation by HPO-P was
      not the basis for enhanced antifungal activity in transgenic plants expressing
      the HPO-P gene.

PMID- 11829631
TI  - Novel compounds from Piper methysticum Forst (Kava Kava) roots and their effect
      on cyclooxygenase enzyme.
AB  - Milled Piper methysticum roots were extracted sequentially with hot water and
      methanol. Cyclooxygenase (COX) enzyme inhibitory assay directed purification of
      the methanol extract yielded bornyl esters of 3,4-methylenedioxy cinnamic acid
      (1) and cinnamic acid (2), pinostrobin (3), flavokawain B (4), and 5,7
      dimethoxyflavanone (5). The structures of compounds 1-5 were accomplished by
      spectral experiments. The aqueous extract contained previously reported kava
      lactones, as confirmed by TLC analysis. Compounds 3 and 5 were isolated for the
      first time from kava kava roots. Compound 4 showed the highest COX-I inhibitory
      activity at 100 microg/mL. All the compounds tested gave good COX-I and moderate
      COX-II enzyme inhibitory activities at 100 microg/mL. This is the first report of
      COX-I and -II inhibitory activities for compounds 1-5.

PMID- 11829633
TI  - gamma-Radiation influences browning, antioxidant activity, and malondialdehyde
      level of apple juice.
AB  - Apple juice was gamma-irradiated at 5 degrees C at doses ranging from 0 to 8.9
      kGy and then stored at 5 degrees C for 15 days. Ionizing radiation reduced the
      browning of apple juice and increased antioxidant activity measured by the ferric
      reducing antioxidant power (FRAP) assay. The magnitude of changes increased with
      radiation dose. The level of malondialdehyde (MDA) measured using the
      thiobarbituric acid reactive substrates assay increased at radiation doses above
      2.67 kGy. The browning of irradiated juices increased during storage at 5 degrees
      C, but the irradiated juices were still lighter than controls at the end of
      storage. Differences in FRAP values disappeared during early periods of storage
      while higher MDA levels were observed in irradiated samples during most of the
      storage period. Elimination of suspended matter from apple juice did not alter
      irradiation-induced changes in browning, FRAP, or MDA formation. As compared to
      irradiation conducted at 5 and 20 degrees C, treatment at -15 degrees C was less
      effective in reducing browning and in increasing MDA formation but elevated FRAP
      values. The exclusion of oxygen from juices did not affect the reduction in
      browning due to irradiation but promoted the increase in FRAP values and
      decreased the irradiation-induced MDA formation.

PMID- 11829634
TI  - Stability of virgin olive oil. 1. Autoxidation studies.
AB  - Virgin olive oil samples with similar oxidative stabilities and fatty acid
      compositions were stored for 24 months. Changes in the lipid substrate were
      followed by peroxide value and K(232) measurements. HPLC was used to evaluate
      changes in the alpha-tocopherol, pigment, and squalene contents. Total polar
      phenol content was measured colorimetrically. The loss of alpha-tocopherol and
      carotenoids was comparable with that of polar phenol content, suggesting an
      active participation in autoxidation. The limited role of squalene in
      autoxidation was further confirmed using an olive oil model and in the presence
      of alpha-tocopherol. Pheophytin a degradation was high, although spectrometric
      estimation of chlorophyll content did not indicate so. Evaluation of pheophytin a
      activity at three different levels of addition on the oil model indicated a
      concentration-dependent antioxidant role more pronounced at elevated
      temperatures, which could be partially due to the activity of certain degradation
      products.

PMID- 11829636
TI  - Fungal growth and fusarium mycotoxin content in isogenic traditional maize and
      genetically modified maize grown in France and Spain.
AB  - Fungi of the genus Fusarium are common fungal contaminants of maize and are also
      known to produce mycotoxins. Maize that has been genetically modified to express
      a Bt endotoxin has been used to study the effect of insect resistance on fungal
      infection of maize grains by Fusarium species and their related mycotoxins. Maize
      grain from Bt hybrids and near-isogenic traditional hybrids was collected in
      France and Spain from the 1999 crop, which was grown under natural conditions.
      According to the ergosterol level, the fungal biomass formed on Bt maize grain
      was 4-18 times lower than that on isogenic maize. Fumonisin B(1) grain
      concentrations ranged from 0.05 to 0.3 ppm for Bt maize and from 0.4 to 9 ppm for
      isogenic maize. Moderate to low concentrations of trichothecenes and zearalenone
      were measured on transgenic as well as on non-transgenic maize. Nevertheless,
      significant differences were obtained in certain regions. The protection of maize
      plants against insect damage (European corn borer and pink stem borer) through
      the use of Bt technology seems to be a way to reduce the contamination of maize
      by Fusarium species and the resultant fumonisins in maize grain grown in France
      and Spain.

PMID- 11829635
TI  - Stability of virgin olive oil. 2. Photo-oxidation studies.
AB  - Virgin olive oil samples with similar oxidative stabilities and fatty acid
      compositions were exposed to 12100 lx (25 +/- 1 degrees C) in closed bottles
      until bleached. The observed low changes in the substrate and polar phenols were
      related to oxygen availability. HPLC monitoring showed that pheophytin agradual
      degradation (> 90%) was accompanied by a considerable alpha-tocopherol loss (22
      35%) due to the reaction of the latter with singlet oxygen. No changes were
      recorded for carotenoids, which acted as physical quenchers and light filters.
      Squalene loss was confined (4-12%). Complementary experiments on the activity of
      pheophytin a, using olive oil models, indicated a concentration dependence,
      enhanced by oxygen availability. In closed bottles, the degradation rate constant
      was higher at low amounts of pheophytin a. Squalene was preferentially consumed
      to protect alpha-tocopherol. An urgent change in the practice of packaging is
      needed to preserve the precious characteristics of the product during
      commercialization.

PMID- 11829637
TI  - Improved method for quantifying the avicide 3-chloro-p-toluidine hydrochloride in
      bird tissues using a deuterated surrogate/GC/MS method.
AB  - A method using a deuterated surrogate of the avicide 3-chloro-p-toluidine
      hydrochloride (CPTH) was developed to quantify the CPTH residues in the
      gastrointestinal (GI) tract and breast muscle tissues in birds collected in CPTH
      baited sunflower and rice fields. This method increased the range of a previous
      surrogate/gas chromatography/mass spectroscopy method from 0-2 to 0-20 microg/g
      in tissue samples and greatly simplified the extraction procedure. The modified
      method also sought to increase recoveries over a range of matrix effects
      introduced by analyzing tissues from birds collected in the field, where the GI
      tract contents would be affected by varying diet. The new method was used to
      determine the CPTH concentration in GI tract samples fortified with CPTH-treated
      rice bait to simulate the consumption of varying amounts of treated bait by two
      nontargeted bird species, pigeon (Columbia livia) and house sparrow (Passer
      domesticus). The new method was then used to examine the CPTH concentrations in
      the gizzard contents of the targeted bird species, red-winged black bird
      (Agelaius phoeniceus) and brown-headed cowbird (Molothrus ater), that were
      collected after feeding at a treated bait site. The method proved sufficiently
      sensitive to quantify CPTH in the breast muscle tissues and the gizzard contents
      of red-winged blackbirds and brown-headed cowbirds during an operational baiting
      program. The levels of CPTH determined for these birds in both tissue samples
      were determined to be highly correlated. The appearance of CPTH in the breast
      muscle tissue immediately after feeding was not anticipated. The potential
      secondary hazard posed by the targeted birds to potential scavengers and
      predators was also evaluated.

PMID- 11829638
TI  - Thiabendazole uptake and storage performance of cactus pear [Opuntia ficus-indica
      (L.) Mill. Cv Gialla] fruit following postharvest treatments with reduced doses
      of fungicide at 52 degrees C.
AB  - The storage response of cactus pears [Opuntia ficus-indica Miller (L.) cv.
      Gialla] was investigated over 6 weeks at 6 degrees C, plus an additional week of
      simulated marketing period (SMP) at 20 degrees C, after a 3-min dip treatment
      with thiabendazole (TBZ) at 1000 mg/L at 20 degrees C or 150 mg/L TBZ at 52
      degrees C. Untreated fruits were used as control. Following TBZ treatments at 20
      and 52 degrees C, total residues were recovered from the peel of cactus pear, as
      the concentration of residues in the pulp was negligible. Treatments with 1000
      mg/L TBZ at 20 degrees C resulted in a 2.82 mg/kg residue uptake (active
      ingredient, whole-fruit basis), whereas treatment at 150 mg/L TBZ left 1.09
      mg/kg. TBZ showed great persistence over both storage and SMP: on average, in the
      fruits treated at 20 and 52 degrees C, over 72 and 68%, respectively, of TBZ was
      still present after SMP. Postharvest treatments with 1000 mg/L TBZ at room
      temperature did not affect the expression of slight-to-moderate chilling injury
      (CI), but reduced severe CI by approximately 50% and decay development by 63.4%
      in comparison to those of untreated fruit after SMP. The effectiveness of TBZ was
      much higher with the treatment at 150 mg/L TBZ at 52 degrees C, providing 91%
      control of severe CI and approximately 89% suppression of decay; no treatment
      damage occurred during storage and SMP. External appearance was better in fruit
      treated with 150 mg/L TBZ at 52 degrees C. Respiration rate, titratable acidity,
      soluble solids concentration, and acetaldehyde in the flesh were not
      significantly influenced by treatments. Ethylene production rate and ethanol
      levels in the flesh were significantly higher in the TBZ-treated fruit as opposed
      to those in the untreated control fruit.

PMID- 11829640
TI  - Varietal differentiation of red wines in the Valencian region (Spain).
AB  - Ninety-one young varietal wines from the Valencian community (Spain), made from
      Cabernet Sauvignon, Tempranillo, Monastrell, and Bobal grapes, were tested on the
      basis of 33 variables: 9 conventional parameters, 10 alcohols and polyols, and 14
      esters. Discriminant analysis was used to identify and explain the differences
      among samples, as well as to determine whether it is possible or not to
      differentiate among varieties. This differentiation (100% of the samples) has
      been possible due to the new discriminant analysis based on only 11 main
      variables: total acidity, cis-3-hexenol, methanol, glycerol, 2,3-butanediol,
      isobutyric alcohol, 1-pentanol, acetaldehyde, ethyl propionate, ethyl decanoato,
      and gamma-butyrolactone, which allow differentiating 100% of the 1994 vintage and
      97% of the 1995 vintage.

PMID- 11829639
TI  - Phytosterol content in American ginseng seed oil.
AB  - North American ginseng (Panax quinquefolium L.) oil was saponifed and the
      unsaponifiable matter trimethylsilylated. The phytosterol fraction of hexane
      extracted, air-dried seed was quantified and identified by GC and GC-MS.
      Phytosterol contents (milligrams per 100 g of oil) were as follows: squalene (514
      569), oxidosqualene (8.97-48.2), campesterol (9.96-12.4), stigmasterol (93.2
      113), clerosterol (1.91-2.14), beta-sitosterol (153-186), beta-amyrin (11.7
      19.5), delta(5)-avenasterol (12.4-20.5), delta(5,24(25))-stigmasterol (3.70-.76),
      lupeol (14.4-15.2), delta(7)-sitosterol (12.5-14.6), delta(7)-avenasterol (4.11
      8.09), 24-methylenecycloartanol (1.94-4.76), and citrostadienol (2.50-3.81). Seed
      stratification lowered the phytosterol levels. Oven-drying gave mixed results,
      and phytosterols varied slightly between the 1999 and 2000 harvests.

PMID- 11829641
TI  - Screening for potential pigments derived from anthocyanins in red wine using
      nanoelectrospray tandem mass spectrometry.
AB  - Red wine extracts were screened for potential wine pigments derived from
      anthocyanins, using a combination of nanoelectrospray tandem mass spectrometry
      techniques. Fourteen aglycons were considered to be of anthocyanidin origin on
      the basis of their MS/MS spectra. The proposed structures of the aglycons were
      anthocyanidin C-4 substituted with vinyl linkage between C-4 and the hydroxy
      group at C-5. The anthocyanidin derivatives identified in the wine extracts were
      vinyl, vinylmethyl, vinylformic acid, 4-vinylphenol, 4-vinylguaiacol, and
      vinylcatechin adducts of malvidin as well as vinylformic acid and 4-vinylphenol
      adducts of peonidin and petunidin. The presence of vinyl alcohol, 4
      vinylcatechol, and 4-vinylsyringol adducts of malvidin was also proposed.

PMID- 11829643
TI  - Behaviors of D- and L-lactic acids during the brewing process of sake (Japanese
      rice wine).
AB  - The amounts of D- and L-lactic acids during the brewing process of sake were
      determined by capillary electrophoresis using 2-hydroxypropyl-beta-cyclodextrin
      as a chiral selector. Because L-lactic acid, which prevents the growth of
      nonuseful microorganisms, is a raw material of sake, the ratio of L-lactic acid
      to total lactic acid is almost 1.0 at the initial stage of sake brewing. During
      brewing, the ratio decreased gradually and finally reached 0.39. Yeast
      (Saccharomyces cerevisiae) for sake brewing produced D-lactic acid, but not L
      lactic acid in a culture medium. These results suggest that the decrease in the
      ratio of L-lactic acid to total lactic acid during sake brewing resulted in D
      lactic acid production by yeast. The ratios in 18 brands of sake obtained
      commercially ranged from 0.23 to 0.78. The levels of D-lactic acid in sake (140
      274 mg/L) were in a narrower range than those of L-lactic acid (61-461 mg/L).
      Although the D-lactic acid level in sake did not correspond to total lactic acid
      level, the L-lactic acid level correlated well with total lactic acid level (R(2)
      = 0.867). These results suggest that the ratio of L-lactic acid to total lactic
      acid in sake reflected the amount of L-lactic acid added at the initial stage of
      sake brewing.

PMID- 11829642
TI  - Isolation and quantitative analysis of phenolic antioxidants, free sugars, and
      polyols from mango (Mangifera indica L.) stem bark aqueous decoction used in Cuba
      as a nutritional supplement.
AB  - An aqueous decoction of mango (Mangifera indica L.) stem bark has been developed
      in Cuba on an industrial scale to be used as a nutritional supplement, cosmetic,
      and phytomedicine. Previously we reported its antioxidant activity, and we
      concluded that the product could be useful to prevent the production of reactive
      oxygen species and oxidative tissue damage in vivo. A phytochemical investigation
      of mango stem bark extract has led to the isolation of seven phenolic
      constituents: gallic acid, 3,4-dihydroxy benzoic acid, gallic acid methyl ester,
      gallic acid propyl ester, mangiferin, (+)-catechin, (-)-epicatechin, and benzoic
      acid and benzoic acid propyl ester. All structures were elucidated by ES-MS and
      NMR spectroscopic methods. Quantitative analysis of the compounds has been
      performed by HPLC, and mangiferin was found to be the predominant component.
      Total polyphenols were assayed also by the Folin-Ciocalteu method. The free
      sugars and polyols content was also determined by GC-MS.

PMID- 11829644
TI  - Characterization of char from the pyrolysis of tobacco.
AB  - Pyrolysis of tobacco was studied in oxidative and nonoxidative (inert)
      environments at atmospheric pressure and temperatures ranging from 150 to 750
      degrees C. The objective was to study the effect of pyrolysis conditions on the
      characteristics of the solid residue, i.e., char. The char was characterized
      using cross-polarization (13)C nuclear magnetic resonance (CPMAS NMR), Fourier
      transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), the
      Brunauer-Emmett-Teller (BET) surface area, and the elemental composition. The
      char yield from pyrolysis (i.e., nonoxidative) decreased sharply with an increase
      in temperature to ca. 22% (dry, ash-free basis) at high temperatures. In
      oxidative pyrolysis, i.e., in 5% oxygen, the char was completely oxidized above
      600 degrees C. The gaseous product from pyrolysis at high temperatures contained
      a significant concentration of hydrogen. The surface area of the char was low,
      with a maximum of 8 m(2)/g at 400 degrees C. SEM analysis indicated that
      pyrolysis of the tobacco led to a gradual accumulation of inorganic crystals on
      the exposed surfaces, and some constituents also melted, resulting in the
      formation of vesicles by evolving gas. NMR analysis showed significant changes in
      pectin and sugar constituents of the tobacco and breaking of glycosidic bonds of
      cellulose at 300-500 degrees C before the char became predominantly aromatic at
      high temperatures. FTIR results showed a continuous decrease in the intensity of
      the OH stretch with temperature and the aromatic character to be at maximum at
      550-650 degrees C. The H/C ratio of the char decreased continuously with
      temperature, while the O/C ratio became constant above 300 degrees C due to the
      presence of oxides and carbonates in the char. The results are consistent with
      the analysis of the evolved gases.

PMID- 11829645
TI  - Characterization of copper/zinc-superoxide dismutase from Pagrus major cDNA and
      enzyme stability.
AB  - A full-length cDNA of 794 bp encoding a putative copper/zinc-superoxide dismutase
      (Cu/Zn-SOD) from Pagrus major was cloned by the PCR approach. Nucleotide sequence
      analysis of this cDNA clone revealed that it comprises a complete open reading
      frame coding for 154 amino acid residues. The deduced amino acid sequence showed
      high similarity (53-91%) with the sequences of Cu/Zn-SOD from other species.
      Computer analysis of the residues required for coordinating copper (His-47, 49,
      64, and 121) and zinc (His-64, 72, 81, and Asp-84), as well as the two cysteines
      (58 and 147) that form a single disulfide bond, were well conserved among all
      reported Cu/Zn-SOD sequences. To further characterize the Pagrus major Cu/Zn-SOD,
      the coding region was subcloned into an expression vector, pET-20b(+), and
      transformed into Escherichia coli BL21(DE3). The expression of the Cu/Zn-SOD was
      confirmed by enzyme activity stained on a native-gel and purified by Ni(2+)
      nitrilotriacetic acid Sepharose superflow. Dimer was the major form of the enzyme
      in equilibrium. The dimerization of the enzyme was inhibited under acidic pH
      (below 4.0 or higher than 10.0). The half-life was 8.6 min and the inactivation
      rate constant (k(d)) was 9.69 x 10(-2) min(-1) at 70 degrees C. The enzyme
      activity was not significantly affected under 4% SDS or 0.5 M imidazole. The
      enzyme was resistant to proteolysis by both trypsin and chymotrypsin.

PMID- 11829646
TI  - Fate of spinosad in litter and soils of a mixed conifer stand in the Acadian
      forest region of New Brunswick.
AB  - Spinosad is a natural insecticide, produced via fermentation culture of the
      actinomycete Saccharopolyspora spinosa, with potential use against a number of
      forest pests including spruce budworm (Choristoneura fumiferana [Clem]).
      Persistence of spinosad was determined in terrestrial fate experiments conducted
      within a semimature stand of black spruce (Picea mariana [Mill.]) and balsam fir
      (Abies balsamea [L]) in the Acadian forest region of New Brunswick, Canada.
      Results of experiments established under full coniferous canopy and in a canopy
      opening indicated that spinosad dissipated rapidly following hyperbolic kinetics
      in both litter and soils and was not susceptible to leaching. Time to 50%
      dissipation estimates for spinosyn A ranged from 2.0 to 12.4 days depending upon
      matrix and experimental conditions. Spinosyn D dissipated to levels below
      quantitation limits (0.02 microg/g of dry mass) within 7 days in all cases.
      Sporadic low-level detection of the demethylated metabolites suggested that
      parent compounds were degraded in situ.

PMID- 11829647
TI  - Volatile components of peel and leaf oils of lemon and lime species.
AB  - Peel and leaf oils of 43 taxa of lemons and limes were obtained from fruits and
      leaves collected from trees submitted to the same pedoclimatic and cultural
      conditions. Their chemical composition was investigated by capillary GC, GC-MS,
      and (13)C NMR, and the results were submitted to principal component analysis to
      check for chemical variability. Three major chemotypes were distinguished for
      lemon peel oils: limonene; limonene/beta-pinene/gamma-terpinene; and
      limonene/linalyl acetate/linalool. Two chemotypes were identified for lemon leaf
      oils: limonene/beta-pinene/geranial/neral and linalool/linalyl acetate/alpha
      terpineol. In lime peel oils, four chemotypes were distinguished: limonene;
      limonene/gamma-terpinene; limonene/beta-pinene/gamma-terpinene; and
      limonene/gamma-terpinene/beta-pinene/oxygenated products. Four others were
      identified for lime leaf oils: beta-pinene/limonene; limonene/geranial/neral;
      limonene/linalool/citronellal; and limonene/sabinene/citronellal/linalool. These
      results were interpreted using principal component analysis.

PMID- 11829648
TI  - Generation of Maillard compounds from inulin during the thermal processing of
      Agave tequilana Weber Var. azul.
AB  - During the cooking process of Agave tequilana Weber var. azul to produce tequila,
      besides the hydrolysis of inulin to generate fermentable sugars, many volatiles,
      mainly Maillard compounds, are produced, most of which may have a significant
      impact on the overall flavor of tequila. Exudates (agave juice) from a tequila
      company were collected periodically, and color, Brix, fructose concentration, and
      reducing sugars were determined as inulin breakdown took place. Maillard
      compounds were obtained by extraction with CH(2)Cl(2), and the extracts were
      analyzed by GC-MS. Increments in color, Brix, and reducing sugars were observed
      as a function of time, but a decrease in fructose concentration was found. Many
      Maillard compounds were identified in the exudates, including furans, pyrans,
      aldehydes, and nitrogen and sulfur compounds. The most abundant Maillard
      compounds were methyl-2-furoate, 2,3-dihydroxy-3,5-dihydro-6-methyl-4(H)-pyran-4
      one, and 5-(hydroxymethyl)furfural. In addition, a series of short- and long
      chain fatty acids was also found. A large number of the volatiles in A. tequilana
      Weber var. azul were also detected in tequila extracts, and most of these have
      been reported as a powerful odorants, responsible for the unique tequila flavor.

PMID- 11829649
TI  - Aroma composition changes in early season grapefruit juice produced from thermal
      concentration.
AB  - Differences in aroma components and total volatiles between a single
      unpasteurized Marsh grapefruit juice and its 65 Brix concentrate reconstituted to
      10 Brix were examined using GC-olfactometry (GC-O) and GC-FID. Total volatiles
      (FID) in the reconstituted concentrate were reduced to less than 5% of initial
      values, but 57% of total aroma (GC-O) remained. Forty-one aroma-active compounds
      were observed in unpasteurized single strength juice, whereas 27 components were
      found in the unflavored reconstituted concentrate. Aroma-active compounds were
      classified into grapefruit/sulfury, sweet/fruity, fresh/citrusy,
      green/fatty/metallic, and cooked/meaty groups. Five of six components in the
      sweet/fruity and 14 of 18 green/fatty/metallic components survived thermal
      concentration. However, only 4-mercapto-4-methyl-2-pentanone in the
      grapefruit/sulfury group, and linalool and nootkatone from the fresh/citrusy
      group, were found in the reconstituted concentrate. Methional was the only aroma
      compound in the cooked/meaty category found in both juice types. beta-Damascenone
      and 1-p-menthen-8-thiol were found only in the reconstituted concentrate. 4
      Mercapto-4-methyl-2-pentanol was found for the first time in grapefruit juice.

PMID- 11829650
TI  - Maillard reaction induced lactose attachment to bovine beta-lactoglobulin:
      electrospray ionization and matrix-assisted laser desorption/ionization
      examination.
AB  - Nonenzymatic attachment of lactose to beta-lactoglobulin (beta-Lg) was
      investigated under different conditions. Solubilized conditions, dry environment,
      and a combination of dry and solubilized environments, were examined for their
      effects on lactosylation. Temperatures ranging from 50 to 65 degrees C and time
      intervals between 1 h and 4 days were used. Electrospray ionization (ESI) and
      matrix-assisted laser desorption/ionization (MALDI) mass spectrometry were
      implemented to examine the reaction products. Maximum attachment efficiency
      occurred at 65 degrees C held for 3 h in dry-way conditions. Incubations held for
      long periods of time under dry-way conditions suggest possible denaturation. Both
      ESI and MALDI data suggest beta-Lg removal in the solubilized samples held for
      long periods of time. A combination of solubilized and dry environments led to
      very similar mass spectrogram results over time.

PMID- 11829651
TI  - Relationship between meat structure, water mobility, and distribution: a low
      field nuclear magnetic resonance study.
AB  - Nuclear magnetic resonance (NMR) measurements were carried out on pork
      longissimus muscle, which pre rigor had been manipulated to various muscle
      lengths, to investigate the relationship between the microstructure of meat and
      the NMR T(2) relaxation. Distributed exponential analysis of the NMR T(2)
      relaxation data revealed the existence of three distinct water populations:
      T(2b), T(21), and T(22). A high, significant correlation was found between the
      T(21) time constant and the sarcomere length (r = 0.84) and calculated ration of
      myofilament lattice volume in the I-band and A-band regions, respectively (r =
      0.84), considering sigmoid relationships. The result implies that the T(21) time
      constant mainly is determined by the structure of the myofilament lattice and so
      strongly supports a previously proposed theory that the T(21) population
      corresponds to water located within a highly organized myofibrillar protein
      matrix including actin and myosin filament structures. A high correlation was
      also found between the T(22) population and the water-holding capacity (WHC) (r =
      0.76), which suggests that the WHC is mainly determined by the amount of loosely
      bound extramyofibrillar water. However, the correlation between NMR T(2)
      parameters and WHC was further increased (r = 0.84) by including the T(21) time
      constant in the correlation analysis. This implies that the formation of drip
      loss is an ongoing process involving the transfer of water from myofibrils to the
      extracellular space and is affected by structural features at several levels of
      organization within the muscle tissue. This study demonstrates the advantages of
      NMR T(2) relaxation as an effective technique for obtaining further understanding
      of the relationship between the microstructure of meat, its WHC, water mobility,
      and water distribution.

PMID- 11829652
TI  - Thermal denaturation of myofibrillar proteins of striated and smooth adductor
      muscles of scallop (Zygochlamys patagonica). A differential scanning calorimetric
      study.
AB  - Denaturation of proteins from striated and smooth muscles of scallop (Zygochlamys
      patagonica) was studied with differential scanning calorimetry (DSC) by
      monitoring maximum temperatures of transition and denaturation enthalpies. DSC
      thermograms of both striated and smooth whole muscles showed two transitions:
      Tmax 55.0, 79.2 degrees C; and Tmax 54.7, 78.7 degrees C, respectively. The DSC
      thermograms of myofibrils and actomyosin were similar to those corresponding to
      their respective whole muscles. As pH and ionic strength increased, the thermal
      stability of whole muscles decreased. The pH increase (5.0-8.0) significantly (p
      < 0.01) decreased the denaturation enthalpies (deltaH total, deltaH peakI, and
      deltaH peakII) of whole striated muscles. A significant decrease (p < 0.05) in
      the deltaH total and the deltaH peakI was also observed in DSC thermograms of
      smooth muscles at pH 8.0. Denaturation enthalpies (deltaH total and deltaH peakI)
      significantly decreased (p < 0.01) when the ionic strength increased from 0.05 to
      0.5 in both types of muscles. Striated muscles were more affected than smooth
      muscles by changes in the chemical environment.

PMID- 11829653
TI  - Characterization of the lipoxygenases in some olive cultivars and determination
      of their role in volatile compounds formation.
AB  - Enzymatic extracts from olive pulp (Olea europea L.) were used to characterize
      lipoxygenase (LOX) activity in order to determine its role in the biogenesis of
      the volatile compounds that influence the aroma of extra virgin olive oil. The
      LOX activity was tested spectrophotometrically at an optimal pH of 6.0 in three
      olive cultivars, Ascolana Tenera, Kalamata, and FS17. The trend of the LOX
      activity was determined as a function of pH and temperature; the kinetic
      constants of the enzyme were also determined. The highest LOX activity was
      observed in the FS17 fruit, which had the highest concentrations of C(5) and C(6)
      compounds (aldehydes, alcohols, and ketones), followed by Kalamata and Ascolana
      T., respectively. Given the direct relationship between enzymatic activity and
      the quantity of aromas measured in the fruit, it is hypothesized that olive LOX
      is involved in the formation of C(5) and C(6) volatile compounds. To study the
      mechanism of the movement of the aromas from the fruit to the oil, which was
      obtained by simple mechanical extraction, the headspace of the oil for each
      cultivar was analyzed as well as the aromatic composition in order to compare it
      with the aromas of the fruit.

PMID- 11829654
TI  - Potential antioxidant capacity of sulfated polysaccharides from the edible marine
      brown seaweed Fucus vesiculosus.
AB  - Fucus vesiculosus was sequentially extracted with water at 22 degrees C (fraction
      1 (F1)) and 60 degrees C (F2), and with 0.1 M HCl (F3) and 2 M KOH (F4) at 37
      degrees C. Soluble fractions (42.3% yield) were composed of neutral sugars (18.9
      48 g/100 g), uronic acids (8.8-52.8 g/100 g), sulfate (2.4-11.5 g/100 g), small
      amounts of protein (< 1-6.1 g/100 g), and nondialyzable polyphenols (0.1-2.7
      g/100 g). The main neutral sugars were fucose, glucose, galactose, and xylose.
      Infrared (IR) spectra of the fractions showed absorption bands at 820-850 and
      1225-1250 cm(-1) for sulfate. F1, F2, and F4 also exhibited an absorption band at
      1425 cm(-1), due to uronic acids, and their IR spectra resembled that of
      alginate. F3 had an IR spectrum similar to that of fucoidan with an average
      molecular weight of 1.6 x 10(6) Da, calculated by molecular exclusion high
      performance liquid chromatography. The presence of fucose in this polysaccharide
      was confirmed by (1)H NMR spectroscopy. This fraction showed the highest
      potential to be antioxidant by the ferric reducing antioxidant power (FRAP)
      assay, followed by the alkali- and water-soluble fractions. Sulfated
      polysaccharides from edible seaweeds potentially could be used as natural
      antioxidants by the food industry.

PMID- 11829655
TI  - Extraction of pharmaceutical components from Ginkgo biloba leaves using
      supercritical carbon dioxide.
AB  - Ginkgo biloba extract (GBE) has many remarkable pharmacological and clinical
      effects, and it is the most frequently used product as a phytomedicine in many
      countries. The combination of primary extraction with 70% ethanol followed by
      extraction using supercritical carbon dioxide provides an efficient and
      economical means for obtaining flavonoids and terpenoids from Ginkgo biloba
      leaves. The supercritical fluid extraction (SFE) is affected by pressure,
      temperature, and the concentration of modifier in the extractant. At the most
      favorable experimental conditions of 300 MPa, 60 degrees C, and carbon dioxide
      containing 5% ethanol as modifier, the yield of GBE powder is 2.1% (based on the
      air-dry weight of Ginkgo biloba leaves) compared to a yield of only 1.8% by
      conventional solvent extraction. The contents of flavonoids and terpenoids in SFE
      products are 35.9% and 7.3%, respectively, which are significantly higher than
      the general standards of 24% and 6%, respectively.

PMID- 11829656
TI  - Inhibitory effects of anthocyanins and other phenolic compounds on nitric oxide
      production in LPS/IFN-gamma-activated RAW 264.7 macrophages.
AB  - Flavonoids have been reported to lower oxidative stress and possess beneficial
      effects on cardiovascular diseases and chronic inflammatory diseases associated
      with nitric oxide (NO). Common phenolic compounds, including phenolic acids,
      flavonols, isoflavones, and anthocyanins, present in fruits were investigated for
      their effects on NO production in LPS/IFN-gamma-activated RAW 264.7 macrophages.
      Phenolic compounds at the range of 16-500 microM that inhibited NO production by
      > 50% without showing cytotoxicity were the flavonols quercetin and myricetin,
      the isoflavone daidzein, and the anthocyanins/anthocyanidins pelargonidin,
      cyanidin, delphinidin, peonidin, malvidin, malvidin 3-glucoside, and malvidin 3,5
      diglucosides. Anthocyanins had strong inhibitory effects on NO production.
      Anthocyanin-rich crude extracts and concentrates of selected berries were also
      assayed, and their inhibitory effects on NO production were significantly
      correlated with total phenolic and anthocyanin contents. This is the first study
      to report the inhibitory effects of anthocyanins and berry phenolic compounds on
      NO production.

PMID- 11829657
TI  - The effect of mashing on malt endoproteolytic activities.
AB  - During malting and mashing, the proteinases of barley (Hordeum vulgare L.) and
      malt partially hydrolyze their storage proteins. These enzymes are critical
      because several aspects of the brewing process are affected by the soluble
      proteins, peptides and/or amino acids that they release. To develop improved
      malting barleys and/or malting and brewing methods, it is imperative to know
      whether and when the green malt endoproteinases are inactivated during malting
      and mashing. These enzyme activities are totally preserved during kilning and, in
      this study, we have determined when they were inactivated during mashing. Samples
      were removed from experimental mashes that mirrored those used in commercial
      breweries and their endoproteolytic activities were analyzed. The malt
      endoproteinases were stable through the 38 degrees C protein rest phase, but were
      quickly inactivated when the mash temperature was raised to 72 degrees C for the
      conversion step. All of the proteinase activities were inactivated at about the
      same rate. These findings indicate that the soluble protein levels of worts can
      be varied by adjusting the protein rest phase of mashing, but not by altering the
      conversion time. The rates of hydrolysis of individual malt proteins probably
      cannot be changed by altering the mash temperature schedule, since the main
      enzymes that solubilize these proteins are affected similarly by temperature.

PMID- 11829658
TI  - Triterpene saponins from debittered quinoa (Chenopodium quinoa) seeds.
AB  - Twelve triterpene saponins have been isolated from the debittered seeds of quinoa
      (Chenopodium quinoa), and their structures were characterized on the basis of
      hydrolysis and spectral data, especially NMR evidence. Among them, three
      compounds, including 3-O-beta-D-glucuropyranosyl oleanolic acid (1), 3-O-beta-D
      glucopyranosyl-(1-->3)-alpha-L-arabinopyranosyl hederagenin (2), and the new
      compound 3-O-beta-D-glucopyranosyl-(1-->3)-alpha-L-arabinopyranosyl-30-O-methyl
      spergulagenate 28-O-beta-D-glucopyranosyl ester (3), are identified for the first
      time from quinoa seeds. The other isolated saponins have been previously reported
      in quinoa.

PMID- 11829659
TI  - Effects of peroxidase on hyperlipidemia in mice.
AB  - To observe the effects of peroxidase on hyperlipidemia, mice were fed a diet high
      in cholesterol and fat. At the same time, the mice were given different-purity
      peroxidase (radish juice, crude radish peroxidase, and horseradish peroxidase),
      and their serum cholesterol, triglyceride, blood glucose, amylase, and esterase
      activities, and malondialdehyde in the mouse small intestines and livers, were
      tested after 15 days on the test diets. The results showed that peroxidase
      decreased the levels of total serum cholesterol, triglyceride, blood glucose, and
      lipid peroxidation in the small intestines and livers of hyperlipidemic mice.
      This suggests that peroxidase may be a contributing factor in the prevention of
      hyperlipidemia.

PMID- 11829660
TI  - Iron derivatives from casein hydrolysates as a potential source in the treatment
      of iron deficiency.
AB  - The properties of an Fe(3+)-peptide complex containing 5.6% Fe, obtained by the
      reaction of ferric chloride with an enzymatic hydrolysate of casein, are
      described. The major site of iron binding corresponds primarily to the
      carboxylate groups and to a lesser extent to the peptide bonds. The Fe(3+)
      peptide complex is insoluble at acid pH and completely soluble at neutral to
      alkaline pH. When soluble, the Fe(3+) is tightly bound to the complex peptide
      mixture but can be displaced and complexed by a low molecular weight ligand such
      as cysteine. Its efficacy in relation to iron sulfate was compared in rats. Both
      iron sources were administrated in Milli-Q water by gastric gavage to male Wistar
      rats (180-200 g) after an 18 h fast with water ad libitum. Fe(3+) from the Fe(3+)
      peptide complex was transferred to the blood in a dose-dependent manner (1-8 mg
      of Fe/kg), and the serum iron levels were significantly higher (p < 0.001) than
      in a similar group of rats treated with iron sulfate. In the comparative kinetics
      experiments, the rats received 4 mg of Fe/kg. Both iron sources presented maximum
      absorption, as indicated by the elevation of serum iron levels, 30 min after
      administration, and the AUC(0)(-->2h) of the Fe(3+)-peptide complex was
      significantly higher (p < 0.05) than that observed with iron sulfate. The
      simultaneous administration of free peptides (0-192 mg) with the Fe(3+)-peptide
      complex or iron sulfate did not modify the extent of absorption of iron from both
      sources, suggesting that the absorption is due to the complex formed and probably
      not to exchange reactions in the gastrointestinal tract. In the hemoglobin
      repletion experiments carried out on newly weaned rats with anemia induced by a
      low-iron diet, supplementation of the diet with the the Fe(3+)-peptide complex
      was as efficient as supplementation with iron sulfate in the conversion from diet
      to hemoglobin iron. These results, taken together, suggest that the Fe(3+)
      peptide complex is a potential compound for use as an iron source in biological
      situations.

PMID- 11829661
TI  - High-oleic peanuts are not different from normal peanuts in allergenic
      properties.
AB  - High-oleic peanuts are known for a high content of oleic fatty acid. However, it
      is not known whether high-oleic peanuts are different from normal chemistry
      peanuts in levels of allergenicity and end-product adducts (i.e., products cross
      linked with proteins). For this purpose, four different peanut cultivars
      (Florunner, Georgia Green, NC 9, and NC 2) were evaluated and compared with high
      oleic peanuts (SunOleic 97R). Adducts such as AGE/CML from Maillard reactions and
      MDA/HNE from lipid oxidation were determined, respectively, in ELISA, using
      polyclonal antibodies. Allergenicity was determined based on IgE binding and T
      cell proliferation. Results showed that raw high-oleic peanuts were not different
      from normal peanuts in adduct levels. After roasting, CML and HNE levels remained
      unchanged, but an increased and similar amounts of AGE adducts were found in all
      peanuts. MDA also increased but not in high-oleic peanuts. This suggests that
      high-oleic peanuts are more stable to lipid oxidation than others during heating.
      Despite this, high-oleic peanuts did not differ from normal peanuts in IgE
      binding and T-cell proliferation. It was concluded that a high content of oleic
      fatty acid has no effect on peanut allergenicity and that high-oleic peanuts do
      not give a higher or lower risk of allergy than normal peanuts.

PMID- 11829662
TI  - Concentration effects in myoglobin-catalyzed peroxidation of linoleate.
AB  - The concentration of the free fatty acid anion linoleate was found to be
      important for the pro-oxidative activity of metmyoglobin, MbFe(III), and for
      mixtures of metmyoglobin and hydrogen peroxide, MbFe(III)/H(2)O(2), to yield
      perferrylmyoglobin, (*)MbFe(IV)=O, whereas for ferrylmyoglobin, MbFe(IV)=O, no
      concentration effect was noted as studied in linoleate emulsions (pH 7.4 and 25
      degrees C). Determination of conjugated dienes using second-derivative absorption
      spectroscopy, changes in Soret band absorbance, and spin-trapping ESR
      spectroscopy with alpha-(4-pyridyl-1-oxide)-N-tert-butyl nitrone (POBN) as the
      spin trap were used to evaluate the pro-oxidative activity of myoglobins. At a
      linoleate (LA)/heme protein (HP) ratio of 100, no MbFe(III)-induced linoleate
      peroxidation was observed, as MbFe(III) was converted to its non-pro-oxidative
      low-spin derivative, hemichrome, independently of the presence of H(2)O(2). At
      higher LA/HP ratios, linoleate peroxidation was initiated by the addition of
      MbFe(III), both in the presence and in the absence of H(2)O(2). This proceeded
      with denaturation of MbFe(III), as followed by changes in Soret absorption band,
      which most probably release or expose the heme group to the environment and
      thereby permit hematin-induced lipid peroxidation. The obtained results show that
      the mechanism by which MbFe(IV)=O initiates linoleate peroxidation is different
      from MbFe(III)- and MbFe(III)/H(2)O(2)-initiated linoleate peroxidation. The
      shift in mechanism between heme protein cleavage of lipid hydroperoxides and
      hematin-induced lipid peroxidation is discussed in relation to oxidative progress
      in biological systems and muscle-based foods.

PMID- 11829663
TI  - Evaluation of the antioxidant properties of free and bound phenolic acids from
      native and malted finger millet (ragi, Eleusine coracana Indaf-15).
AB  - Free and bound phenolic acids were isolated from native and malted finger millet
      (ragi, Eleusine coracana Indaf-15), and their antioxidant properties were
      evaluated. Protocatechuic, gallic, and caffeic acids were found to be the major
      free phenolic acids. A 3-fold decrease was observed in protocatechuic acid
      content, whereas the decrease was marginal in the case of caffeic acid upon 96 h
      of malting. However, the contents of other free phenolic acids such as gallic,
      vanillic, coumaric, and ferulic acids increased. Ferulic, caffeic, and coumaric
      acids were found to be the major bound phenolic acids, and a 2-fold decrease was
      observed in their contents upon 96 h of malting. The antioxidant activity of a
      free phenolic acid mixture was found to be higher compared to that of a bound
      phenolic acid mixture. An increase in antioxidant activity coefficient was
      observed in the case of free phenolic acids from 770.0 +/- 7.8 to 1686.0 +/-
      16.0, whereas the same was decreased from 570.0 +/- 6.0 to 448.0 +/- 4.5 in bound
      phenolic acids upon 96 h of malting. Therefore, the antioxidant capacity of
      phenolic acids changes during the malting of ragi.

PMID- 11829664
TI  - Changes in fruit antioxidant activity among blueberry cultivars during cold
      temperature storage.
AB  - Antioxidant activity, total phenolic content, anthocyanin content, and six other
      fruit characters including titratable acid concentration, soluble solids,
      firmness, and percentage of bruised berries were determined for nine blueberry
      (Vaccinium L. sp.) cultivars at harvest and at various postharvest intervals
      after storage at 5 degrees C. Berries from MSU-58, Brigitta, and Legacy stored
      successfully for 7 weeks, Bluegold stored for 3-5 weeks, Bluecrop, Elliott, and
      Nelson stored for 3 weeks, and Jersey and Little Giant stored for fewer than 3
      weeks. During the time they retained marketable quality, one cultivar (MSU-58)
      demonstrated a 29% increase in antioxidant activity. None of the cultivars showed
      a significant decrease from the harvest antioxidant activity value during
      storage. Antioxidant activity, total phenolic content, and anthocyanin content
      were strongly correlated with each other (r = 0.87-0.99, P < 0.01). All three
      parameters were moderately correlated with soluble solids (r = 0.47, P < or
      =0.05; r = 0.44, P < or = 0.05; and r = 0.64, P < or = 0.01, respectively), and
      antioxidant activity and total phenolic content were both moderately correlated
      with pH (r = 0.53 and 0.49, respectively; P < or = 0.05). However, antioxidant
      activity, total phenolic content, and anthocyanin content showed no correlation
      with firmness, percent severely bruised berries, or weight loss. Antioxidant
      activity and total phenolic content at harvest both correlated with titratable
      acidity at harvest (r = 0.68, P < or = 0.05 and r = 0.70, P < or = 0.05,
      respectively) on a cultivar mean basis. Berries from Elliott were also harvested
      from plants at two levels of bush ripeness (30-50% and 60-80% ripe berries on
      plants) and separated into three fruit maturity classes on the basis of percent
      blue color. The level of bush ripeness had no significant effect on antioxidant
      activity, total phenolic content, or anthocyanin content; however, fruit maturity
      had a significant effect on antioxidant activity, total phenolic content, and
      anthocyanin content, and bush ripeness x fruit maturity interactions were
      significant for these three traits. Berries with 50-75% blue coloration harvested
      from bushes with 60-80% mature fruit showed a significant increase in antioxidant
      activity, total phenolic content, and anthocyanin content during the first 3
      weeks in storage. Our results demonstrate that increases in antioxidant activity,
      total phenolic content, and anthocyanin content may occur in the blueberry during
      cold storage and are cultivar-dependent. The increases that occur in immature
      fruit, such as in Elliott, may be advantageous for producers who wish to delay
      marketing of the fruit.

PMID- 11829665
TI  - In vitro efficacies of phosphorolytic enzymes synthesized in mycelial cells of
      Aspergillus niger AbZ4 grown by a liquid surface fermentation.
AB  - Activities of phytase, a pH 6.0 optimum nonspecific phosphomonoesterase and
      phosphodiesterase assayed toward bis(p-nitrophenyl)phosphate (phosphodiesterase
      I) and against p-nitrophenylphosphorylcholine (phosphodiesterase II), were
      partially purified from mycelial extracts of Aspergillus niger AbZ4 cultivated on
      a molasses medium by a liquid surface fermentation method. After elimination of
      phosphate from the medium, 7.3- and 3.5-fold enhancements in specific activities
      of phytase and phosphodiesterase II were observed. Efficacies of mycelial protein
      fractions in dephosphorylating a wheat-based broiler feed were determined in
      vitro according to a procedure that simulated digestion in the intestinal tract
      of poultry. The addition of 0.052 mg of protein from fractions, each of which was
      high in either pH 6.0 optimum phosphomonoesterase, phosphodiesterase I,
      phosphodiesterase II, or phytase per gram of a feed sample resulted in the
      enhancement of phosphorus release by 10, 11, 27, and 88%, respectively. In the
      presence of an excess of commercial phytase, the addition of the mycelial
      fraction high in phytase increased the dephosphorylation rate by 56%. The
      fraction high in phosphodiesterase II enhanced feed dephosphorylation by 8% in
      the presence of an excess of commercial phytase and commercial acid phosphatase.

PMID- 11829666
TI  - Early weaning of calves using feedstuffs. A rationalization based on inhibition
      of lipolysis.
AB  - The ability of broll (a combination of the wheat-milling byproducts bran and
      pollard, i.e., a mixture of wheat bran, husk, and flour) and blackstrap molasses
      (an ingredient of calf feed) to inhibit calf pregastric lipase (CPGL)-catalyzed
      hydrolysis of tributyrylglycerol (TBG) has been studied in vitro. Lipolysis was
      measured at pH 6.5 and 37 degrees C (CPGL at 0.02 mg/mL) with stirring at 300
      rpm. The broll soaked in Bis-Tris buffer (50 mM, pH 6.5) at 4 degrees C for
      either 24 h or 15 min, and then added to an emulsion containing TBG, before
      initiation of the reaction by addition of CPGL, exhibited 22% inhibitory effect.
      A solution of blackstrap molasses (50%, v/v) exhibited inhibitory effects of 50%
      in the absence and 45% in the presence of Bis-Tris buffer. The initial rate of
      lipolysis in the presence of the dialyzed molasses retentate (10%, v/v) increased
      a little, compared with the same amount of crude molasses, from a mean value of
      69% to a mean value of 74%. The results have been discussed in terms of the
      chemical nature and composition of broll and molasses and their roles as
      components of feedstuffs used in development of the rumen in early weaning of
      calves.

PMID- 11829667
TI  - Seaweed accelerates the excretion of dioxin stored in rats.
AB  - To prevent health problems of humans exposed to dioxin, it is important to
      enhance the fecal excretion of dioxin stored in the body. The effects of seaweed
      such as wakame, hiziki, and kombu on the gastrointestinal absorption and
      reabsorption of 17 types of polychlorinated dibenzo-p-dioxin (PCDD) and
      polychlorinated dibenzofuran (PCDF) congeners was investigated in Wistar rats.
      Rats were fed 4 g of the basal diet or a seaweed diet containing PCDD and PCDF
      standard solution [233 ng of toxic equivalents (TEQ)/kg of body weight] once
      during the experiment period. In the group fed the 10% wakame diet, the levels of
      fecal excretion of PCDD and PCDF congeners were higher (p < 0.01) from days 1 to
      5 by 2.8-fold for 2,3,7,8-TCDD, by 4.0-fold for 1,2,3,7,8-pentaCDD, by 3.4-fold
      for 1,2,3,4,7,8-hexaCDD, by 3.2-fold for 1,2,3,6,7,8-hexaCDD, by 2.5-fold for
      1,2,3,7,8,9-hexaCDD, by 1.7-fold for 1,2,3,4,6,7,8-heptaCDD, by 1.1-fold for
      1,2,3,4,6,7,8,9-octaCDD, by 3.0-fold for 2,3,7,8-tetraCDF, by 3.7-fold for
      1,2,3,7,8-pentaCDF, by 3.7-fold for 2,3,4,7,8-pentaCDF, by 3.2-fold for
      1,2,3,4,7,8-hexaCDF, by 3.0-fold for 1,2,3,6,7,8-hexaCDF, by 3.2-fold for
      1,2,3,7,8,9-hexaCDF, by 2.9-fold for 2,3,4,6,7,8-hexaCDF, by 1.6-fold for
      1,2,3,4,6,7,8-heptaCDF, by 2.2-fold for 1,2,3,4,7,8,9-heptaCDF, and by 1.2-fold
      for 1,2,3,4,6,7,8,9-octaCDF than those of the basal group, respectively. Rats
      were fed 4 g of the basal diet containing PCDD and PCDF standard solution (2991
      ng of TEQ/kg of body weight) once on day 1 and then place on the basal diet for 7
      days. After 1 week, the rats were fed either the basal diet or seaweed diet from
      days 8 to 35. In the group fed the 10% wakame diet, the levels of fecal excretion
      of PCDD and PCDF congeners were higher (p < 0.01 or p < 0.05) during the period
      from days 8 to 35 by 1.7-fold for 2,3,7,8-TCDD, by 1.8-fold for 1,2,3,7,8
      pentaCDD, by 2.0-fold for 1,2,3,4,7,8-hexaCDD, by 1.9-fold for 1,2,3,6,7,8
      hexaCDD, by 1.6-fold for 1,2,3,7,8,9-hexaCDD, by 1.5-fold for 1,2,3,4,6,7,8
      heptaCDD, by 2.0-fold for 2,3,4,7,8-pentaCDF, by 2.1-fold for 1,2,3,4,7,8
      hexaCDF, by 1.9-fold for 1,2,3,6,7,8-hexaCDF, by 1.7-fold for 2,3,4,6,7,8
      hexaCDF, by 1.5-fold for 1,2,3,4,6,7,8-heptaCDF, and by 1.9-fold for
      1,2,3,4,7,8,9-heptaCDF than those of the basal group, respectively. These
      findings suggest that the administration of seaweed such as wakame is efficient
      in preventing the absorption and reabsorption of dioxin from the gastrointestinal
      tract and might be useful in treatment of humans exposed to dioxin.

PMID- 11829669
TI  - Organoarsenical species contents in fresh and processed seafood products.
AB  - A study was carried out to determine organic species of arsenic in the main
      varieties of seafood consumed in the Basque country (Spain). The concentrations
      of arsenobetaine (AB), dimethylarsinic acid (DMA), monomethylarsonic acid (MMA),
      arsenocholine (AC), and tetramethylarsonium ion (TMA(+)) in 64 samples
      corresponding to different food items are presented. The study provides
      information about a possible distribution pattern of organoarsenical species in
      seafood products. AB was detected in all of the samples [0.3-104.1 microg g(-1)
      dry weight (dw)]. DMA was detected in all of the samples except squid and salted
      cod (0.027-1.757 microg g(-1) dw). MMA was detected only in certain fatty fish
      (0.004-0.028 microg g(-1) dw) and bivalves (0.031-0.047 microg g(-1) dw). AC was
      only present in some samples of lean fish (0.014-0.089 microg g(-1) dw), and
      TMA(+) was detected only in anchovy (0.039-0.169 microg g(-1) dw) and crustaceans
      (0.044-0.966 microg g(-1) dw).

PMID- 11829668
TI  - Heavy metal, total arsenic, and inorganic arsenic contents of algae food
      products.
AB  - The total arsenic, inorganic arsenic, lead, cadmium, and mercury contents of 18
      algae food products currently on sale in Spain were determined. The suitability
      of the analytical methodologies for this type of matrix was confirmed by
      evaluating their analytical characteristics. The concentration ranges found for
      each contaminant, expressed in milligrams per kilogram of dry weight, were as
      follows: total arsenic, 2.3-141; inorganic arsenic, 0.15-88; lead, < 0.05-1.33;
      cadmium, 0.03-1.9; and mercury, 0.004-0.04. There is currently no legislation in
      Spain regarding contaminants in algae food products, but some of the samples
      analyzed revealed Cd and inorganic As levels higher than those permitted by
      legislation in other countries. Given the high concentrations of inorganic As
      found in Hizikia fusiforme, a daily consumption of 1.7 g of the product would
      reach the Provisional Tolerable Weekly Intake recommended by the WHO for an
      average body weight of 68 kg. A more comprehensive study of the contents and
      toxicological implications of the inorganic As present in the algae food products
      currently sold in Spain may be necessary, which might then be the basis for the
      introduction of specific sales restrictions.

PMID- 11829675
TI  - Bioweapons preparedness chief discusses priorities in world of 21st-century
      biology. Interview by Rebecca Voelker.

PMID- 11829671
TI  - Metabolism and lack of DNA reactivity of the mycotoxin ochratoxin a in cultured
      rat and human primary hepatocytes.
AB  - It is still unclear whether the carcinogenic mycotoxin ochratoxin A (OTA) is
      bioactivated to DNA-binding metabolites in rodents and humans. Therefore, we have
      incubated cultured rat and human primary hepatocytes with noncytotoxic
      concentrations of (3)H-OTA ranging from 10(-7) to 10(-5) M for 8 h and determined
      its metabolism and covalent DNA binding. In rat hepatocytes, OTA was metabolized
      to small amounts of three products, which were further studied by electrospray
      ionization (ESI)-MS/MS techniques. In addition to 4-hydroxy-OTA, which is a known
      product of OTA biotransformation, two novel metabolites were detected and
      tentatively identified as hexose and pentose conjugates of OTA. The in vitro
      induction with 3-methylcholanthrene (3MC) increased the formation of 4-hydroxy
      OTA but did not alter the formation of the conjugated metabolites. No covalent
      binding of (3)H-OTA or its metabolites to DNA was observed in rat hepatocytes
      with or without 3MC induction with a limit of detection of 2 adducts per 10(9)
      nucleotides. However, the cellular ratio of reduced glutathione to oxidized
      glutathione was significantly decreased by treatment with OTA. In cultured human
      hepatocytes, (3)H-OTA was only very poorly metabolized, and no covalent DNA
      binding was observed. In conclusion, the results of this in vitro study do not
      support the notion that OTA has the potential to undergo metabolic activation and
      form covalent DNA adducts in rodents and humans.

PMID- 11829670
TI  - Development and application of an indirect competitive enzyme-linked immunoassay
      for aflatoxin m(1) in milk and milk-based confectionery.
AB  - High-titer rabbit polyclonal antibodies to aflatoxin M(1) (AFM1) were produced by
      utilizing AFM1-bovine serum albumin (BSA) conjugate as an immunogen. An indirect
      competitive enzyme-linked immunosorbent assay was standardized for estimating
      AFM1 in milk and milk products. To avoid the influence of interfering substances
      present in the milk samples, it was necessary to prepare AFM1 standards in
      methanol extracts of certified reference material (CRM) not containing detectable
      AFM1 (< 0.05 ng/g). The reliability of the procedure was assessed by using CRM
      with AFM1 concentrations of < 0.5 and 0.76 ng/g. Also, assays of milk samples
      mixed with AFM1 ranging in concentration between 0.5 and 50 ng/L gave recoveries
      of > 93%. The relative cross-reactivity with aflatoxins (AF) and ochratoxin A,
      assessed as the amount of AFM1 necessary to cause 50% inhibition of binding, was
      5% for AFB1 and much less for AFB2, AFG1, and AFG2; there was no reaction with
      ochratoxin A. AFM1 contamination was measured in retail milk and milk products
      collected from rural and periurban areas in Andhra Pradesh, India. Of 280 milk
      samples tested, 146 were found to contain < 0.5 ng/mL of AFM1; in 80 samples it
      varied from 0.6 to 15 ng/mL, in 42 samples from 16 to 30 ng/mL, and in 12 samples
      from 31 to 48 ng/mL. Most of the milk samples that contained high AFM1
      concentrations were obtained from periurban locations. The results revealed a
      significant exposure of humans to AFM1 levels in India and thus highlight the
      need for awareness of risk among milk producers and consumers.

PMID- 11829676
TI  - Experts focus on infective agents of bioterrorism.

PMID- 11829677
TI  - Hospital study offers hope of changing lives prone to violence.

PMID- 11829678
TI  - From the Food and Drug Administration.

PMID- 11829681
TI  - Decisions about cervical spine radiography following trauma.

PMID- 11829682
TI  - Decisions about cervical spine radiography following trauma.

PMID- 11829684
TI  - Cost-effectiveness of aircraft safety measures.

PMID- 11829686
TI  - What should the public be told about the risks of ecstasy?

PMID- 11829687
TI  - What should the public be told about the risks of ecstasy?

PMID- 11829689
TI  - Dry eye syndrome in postmenopausal women.

PMID- 11829691
TI  - Responsibilities of physicians and pharmacists in preventing drug interactions.

PMID- 11829693
TI  - Does early identification of deaf newborns lead to later improvements in language
      skills?

PMID- 11829695
TI  - Changes in HIV-related deaths as a function of coding.

PMID- 11829696
TI  - Extraimmunization in children through 2000.

PMID- 11829697
TI  - Quality-of-life and depressive symptoms in postmenopausal women after receiving
      hormone therapy: results from the Heart and Estrogen/Progestin Replacement Study
      (HERS) trial.
AB  - CONTEXT: Postmenopausal hormone therapy is commonly used by women for disease
      prevention, but its effects on quality of life have not been well documented.
      OBJECTIVE: To determine the effect on quality of life of estrogen plus progestin
      therapy used as secondary prevention in women with coronary artery disease.
      DESIGN, SETTING, AND PARTICIPANTS: A total of 2763 postmenopausal women with
      documented coronary artery disease (mean age, 67 years) in the Heart and
      Estrogen/Progestin Replacement Study, a randomized, placebo-controlled, double
      blind trial conducted from January 1993 to July 1998 at outpatient and community
      settings at 20 US clinical centers. INTERVENTION: Participants were randomly
      assigned to receive either 0.625 mg/d of conjugated equine estrogen plus 2.5 mg/d
      of medroxyprogesterone acetate (n = 1380) or placebo (n = 1383) for 36 months.
      MAIN OUTCOME MEASURES: Physical activity, measured by the Duke Activity Status
      Index; energy/fatigue and mental health, measured by RAND scales; and depressive
      symptoms, measured on the Burnam screening scale, at 3 years of follow-up.
      RESULTS: In all patients, scores declined significantly over 3 years for physical
      function (-3.8; P<.001), mental health (-0.6; P =.05), and energy/fatigue (-3.8;
      P<.001), but depressive symptoms were not significantly changed (P =.20). The
      effect of hormone therapy on these measures depended on the presence (n = 434) or
      absence (n = 2325) of flushing at study entry. Women with flushing who were
      assigned to hormone therapy had improved mental health (+2.6 vs - 0.5; P =.04)
      and fewer depressive symptoms (-0.5 vs + 0.007; P =.01) over follow-up compared
      with those assigned to placebo. Women without flushing who were assigned to
      hormone therapy had greater declines in physical function (-4.2 vs -3.3; P =.04)
      and energy/fatigue (-4.6 vs -3.1; P =.03) over follow-up. Quality-of-life scores
      were significantly lower among patients with older age, diabetes, hypertension,
      chest pain, or heart failure. These differences in quality of life among women
      classified by clinical characteristics were much greater than the effects of
      hormone therapy. CONCLUSION: Hormone therapy has mixed effects on quality of life
      among older women. The effects of hormone therapy depend on the presence of
      menopausal symptoms; women without flushing had greater declines in physical
      measures, while women with flushing had improvements in emotional measures of
      quality of life.

PMID- 11829698
TI  - Effects of diet and simvastatin on serum lipids, insulin, and antioxidants in
      hypercholesterolemic men: a randomized controlled trial.
AB  - CONTEXT: Limited information exists on the interaction between diet and 3-hydroxy
      3-methylglutaryl coenzyme A reductase inhibitors (statins) and the interaction's
      effect on serum lipid and lipoprotein levels, insulin sensitivity, and
      circulating antioxidant vitamin and provitamin levels. OBJECTIVE: To evaluate the
      separate and combined effects of diet and simvastatin therapy on serum levels of
      lipids, lipoproteins, antioxidants, and insulin. DESIGN, SETTING, AND
      PARTICIPANTS: Randomized, controlled crossover trial conducted from August 1997
      to June 1998 in 120 previously untreated hypercholesterolemic men aged 35 to 64
      years who were recruited from the community in Turku, southwestern Finland.
      INTERVENTIONS: After a 4- to 6-week placebo run-in period, participants were
      randomly allocated to a habitual diet (n = 60) or dietary treatment group (n =
      60), and each of these groups was further randomized in a double-blind crossover
      fashion to receive simvastatin (20 mg/d) or placebo, each for 12 weeks (n = 30 in
      each group). The main goals of the dietary treatment were to reduce energy intake
      from saturated plus trans-unsaturated fats to no more than 10% by replacing them
      partly with monounsaturated and polyunsaturated fats rich in omega-3 fatty acids
      and to increase intake of fruits, vegetables, and dietary fiber. MAIN OUTCOME
      MEASURES: Changes in levels of total, low-density lipoprotein (LDL), and high
      density lipoprotein (HDL) cholesterol; triglycerides; apolipoprotein B; insulin;
      glucose; and antioxidants at week 12 of each treatment period, compared among the
      4 groups. RESULTS: Dietary treatment decreased levels of total cholesterol by
      7.6% (P<.001), LDL cholesterol by 10.8% (P<.001), HDL cholesterol by 4.9% (P
      =.01), apolipoprotein B by 5.7% (P =.003), serum insulin by 14.0% (P =.02), and
      alpha-tocopherol by 3.5% (P =.04). Simvastatin decreased levels of total
      cholesterol by 20.8%, LDL cholesterol by 29.7%, triglycerides by 13.6%,
      apolipoprotein B by 22.4%, alpha-tocopherol by 16.2%, beta-carotene by 19.5%, and
      ubiquinol-10 by 22.0% (P<.001 for all) and increased levels of HDL cholesterol by
      7.0% (P<.001) and serum insulin by 13.2% (P =.005). Glucose levels remained
      unchanged in all groups. The effects of dietary treatment and simvastatin were
      independent and additive. CONCLUSIONS: A modified Mediterranean-type diet rich in
      omega-3 fatty acids efficiently potentiated the cholesterol-lowering effect of
      simvastatin, counteracted the fasting insulin-elevating effect of simvastatin,
      and, unlike simvastatin, did not decrease serum levels of beta-carotene and
      ubiquinol-10.

PMID- 11829699
TI  - Varicella disease after introduction of varicella vaccine in the United States,
      1995-2000.
AB  - CONTEXT: Before licensure of varicella vaccine in 1995, varicella was a universal
      childhood disease in the United States, causing 4 million cases, 11,000
      hospitalizations, and 100 deaths every year. OBJECTIVE: To examine population
      based disease surveillance data in 3 communities to document the impact of the
      varicella vaccination program. DESIGN, SETTING, AND SUBJECTS: Active surveillance
      for varicella conducted among the populations of Antelope Valley, Calif; Travis
      County, Tex; and West Philadelphia, Pa; from January 1, 1995, to December 31,
      2000. Reporting sites included child care centers, schools, universities,
      physicians, public health clinics, hospitals, emergency departments, and
      households. MAIN OUTCOME MEASURES: Trends in number and rate of varicella cases
      and hospitalizations; varicella vaccine coverage. RESULTS: From 1995 through
      1998, in each surveillance area, the number of verified varicella cases varied
      from year to year with marked springtime seasonality. In 1999, the number and
      rates of varicella cases and hospitalizations declined markedly. From 1995
      through 2000, in Antelope Valley, Travis County, and West Philadelphia, varicella
      cases declined 71%, 84%, and 79%, respectively. Cases declined to the greatest
      extent among children aged 1 to 4 years, but cases declined in all age groups,
      including infants and adults. In the combined 3 surveillance areas,
      hospitalizations due to varicella declined from a range of 2.7 to 4.2 per 100,000
      population in 1995 through 1998 to 0.6 and 1.5 per 100,000 population in 1999 and
      2000, respectively (P =.15). By 2000, vaccine coverage among children aged 19 to
      35 months was 82.1%, 73.6%, and 83.8% in Los Angeles County, Texas, and
      Philadelphia County, respectively. CONCLUSIONS: Varicella disease has declined
      dramatically in surveillance areas with moderate vaccine coverage. Continued
      implementation of existing vaccine policies should lead to further reductions of
      varicella disease in these communities and throughout the United States.

PMID- 11829700
TI  - Relationships between authors of clinical practice guidelines and the
      pharmaceutical industry.
AB  - CONTEXT: Increasing contact has been reported between physicians and the
      pharmaceutical industry, although no data exist in the literature regarding
      potential financial conflicts of interest for authors of clinical practice
      guidelines (CPGs). These interactions may be particularly relevant since CPGs are
      designed to influence the practice of a large number of physicians. OBJECTIVE: To
      quantify the extent and nature of interactions between authors of CPGs and the
      pharmaceutical industry. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional
      survey of 192 authors of 44 CPGs endorsed by North American and European
      societies on common adult diseases published between 1991 and July 1999. One
      hundred authors (52%) provided usable responses representing 37 of 44 different
      CPGs that we identified. MAIN OUTCOME MEASURES: Nature and extent of interactions
      of authors with drug manufacturers; disclosure of relationships in published
      guidelines; prior discussion among authors regarding relationships; beliefs
      regarding whether authors' own relationships or those of their colleagues
      influenced treatment recommendations in guidelines. RESULTS: Eighty-seven percent
      of authors had some form of interaction with the pharmaceutical industry. Fifty
      eight percent had received financial support to perform research and 38% had
      served as employees or consultants for a pharmaceutical company. On average, CPG
      authors interacted with 10.5 different companies. Overall, an average of 81% (95%
      confidence interval, 70%-92%) of authors per CPG had interactions. Similarly, all
      of the CPGs for 7 of the 10 diseases included in our study had at least 1 author
      who had some interaction. Fifty-nine percent had relationships with companies
      whose drugs were considered in the guideline they authored, and of these authors,
      96% had relationships that predated the guideline creation process. Fifty-five
      percent of respondents indicated that the guideline process with which they were
      involved had no formal process for declaring these relationships. In published
      versions of the CPGs, specific declarations regarding the personal financial
      interactions of individual authors with the pharmaceutical industry were made in
      only 2 cases. Seven percent thought that their own relationships with the
      pharmaceutical industry influenced the recommendations and 19% thought that their
      coauthors' recommendations were influenced by their relationships. CONCLUSIONS:
      Although the response rate for this survey was low, there appears to be
      considerable interaction between CPG authors and the pharmaceutical industry. Our
      study highlights the need for appropriate disclosure of financial conflicts of
      interest for authors of CPGs and a formal process for discussing these conflicts
      prior to CPG development.

PMID- 11829701
TI  - Long-term efficacy of platelet glycoprotein IIb/IIIa integrin blockade with
      eptifibatide in coronary stent intervention.
AB  - CONTEXT: In the Enhanced Suppression of the Platelet IIb/IIIa Receptor with
      Integrilin Therapy (ESPRIT) trial, treatment with eptifibatide, a platelet
      glycoprotein IIb/IIIa integrin blocker, was found to reduce the ischemic
      complications of nonurgent coronary stent implantation at 48 hours and 30 days.
      OBJECTIVE: To determine whether eptifibatide treatment continues to provide
      durable, long-term benefit after coronary stent intervention. DESIGN AND SETTING:
      The ESPRIT trial was a randomized, double-blind, placebo-controlled, parallel
      group, crossover-permitted trial conducted from June 1999 through February 2000
      at 92 tertiary care centers in the United States and Canada. PARTICIPANTS: A
      total of 2064 patients scheduled to undergo nonurgent percutaneous coronary
      intervention with stent implantation. INTERVENTION: Patients were randomly
      assigned to receive placebo (n = 1024) or eptifibatide (two 180-microg/kg
      boluses, 10 minutes apart, with a continuous infusion of 2.0 microg/kg per
      minute; n = 1040), started immediately before stent implantation and continued
      for 18 to 24 hours. Patients also received aspirin, heparin, and a
      thienopyridine. MAIN OUTCOME MEASURES: Composite rates of death or myocardial
      infarction (MI) and death, infarction, or target vessel revascularization during
      the 12 months after enrollment. RESULTS: Complete follow-up data were available
      for 988 patients given eptifibatide (95.0%) and 976 patients given placebo
      (95.3%). By 12 months, the composite of death or MI had occurred in 8.0% of
      eptifibatide-treated patients and in 12.4% of placebo-treated patients (hazard
      ratio [HR], 0.63; 95% confidence interval [CI], 0.48-0.83; P =.001). The
      composite rate of death, MI, or target vessel revascularization was 17.5% in
      eptifibatide-treated patients vs 22.1% in placebo-treated patients (HR, 0.76; 95%
      CI, 0.63-0.93; P =.007). CONCLUSIONS: Long-term outcomes of nonurgent coronary
      stent implantation appear to be improved through blockade of the platelet
      glycoprotein IIb/IIIa integrin with eptifibatide.

PMID- 11829702
TI  - Nonspecific medication side effects and the nocebo phenomenon.
AB  - Patients taking active medications frequently experience adverse, nonspecific
      side effects that are not a direct result of the specific pharmacological action
      of the drug. Although this phenomenon is common, distressing, and costly, it is
      rarely studied and poorly understood. The nocebo phenomenon, in which placebos
      produce adverse side effects, offers some insight into nonspecific side effect
      reporting. We performed a focused review of the literature, which identified
      several factors that appear to be associated with the nocebo phenomenon and/or
      reporting of nonspecific side effects while taking active medication: the
      patient's expectations of adverse effects at the outset of treatment; a process
      of conditioning in which the patient learns from prior experiences to associate
      medication-taking with somatic symptoms; certain psychological characteristics
      such as anxiety, depression, and the tendency to somatize; and situational and
      contextual factors. Physicians and other health care personnel can attempt to
      ameliorate nonspecific side effects to active medications by identifying in
      advance those patients most at risk for developing them and by using a
      collaborative relationship with the patient to explain and help the patient to
      understand and tolerate these bothersome but nonharmful symptoms.

PMID- 11829703
TI  - Medical management of advanced heart failure.
AB  - CONTEXT: Advanced heart failure, defined as persistence of limiting symptoms
      despite therapy with agents of proven efficacy, accounts for the majority of
      morbidity and mortality in heart failure. OBJECTIVE: To review current medical
      therapy for advanced heart failure. DATA SOURCES: We searched MEDLINE for all
      articles containing the term advanced heart failure that were published between
      1980 and 2001; EMBASE was searched from 1987-1999, Best Evidence from 1991-1998,
      and Evidence-Based Medicine from 1995-1999. The Cochrane Library also was
      searched for critical reviews and meta-analyses of congestive heart failure.
      STUDY SELECTION: Randomized controlled trials of therapy for 150 patients or more
      were included if advanced heart failure was represented. Other common clinical
      situations were addressed from smaller trials as available, trials of milder
      heart failure, consensus guidelines, and both published and personal clinical
      experience. DATA EXTRACTION: Data quality was determined by publication in peer
      reviewed literature or inclusion in professional society guidelines. DATA
      SYNTHESIS: A primary focus for care of advanced heart failure is ongoing
      identification and treatment of the elevated filling pressures that cause
      disabling symptoms. While angiotensin-converting enzyme inhibitors and beta
      adrenergic agents can slow disease progression and prolong survival, titration
      and tolerability often present challenges. Most patients are not eligible for
      surgical intervention but do benefit from a medical regimen tailored to
      individual clinical and hemodynamic profiles and from heart failure management
      programs that reduce rehospitalization. Survival ranges from 80% at 2 years for
      patients rendered free of congestion to less than 50% at 6 months for patients
      with refractory symptoms, in whom end-of-life options may include hospice care
      and inactivation of implantable defibrillators. CONCLUSIONS: Current management
      of advanced heart failure is based more on consensus than on randomized trials.
      Systematic investigation should address not only new therapies but also
      strategies for selecting and optimizing therapies already available.

PMID- 11829704
TI  - Postmenopausal hormone therapy and quality of life: no cause for celebration.

PMID- 11829709
TI  - Re-emergence of tuberculosis: strategies and treatment.
AB  - Tuberculosis (TB) was declared a global emergency by the WHO in 1993.
      Approximately one third of the world's population is infected with Mycobacterium
      tuberculosis. Despite the availability of effective chemotherapy, 3.5 million TB
      deaths occur each year. In addition to this human cost, TB also represents a
      significant economic burden for developing countries. The worldwide spread of TB
      is mainly caused by the emergence of multidrug-resistant (MDR) M. tuberculosis
      strains, thus underlining the need for novel antimycobacterial drugs with
      improved efficacy. Research in TB chemotherapy, as well as in vaccine
      development, has entered an intense phase in an attempt to combat this disease.

PMID- 11829710
TI  - Therapeutic potential of the bactericidal/permeability-increasing protein.
AB  - Innate immune mechanisms respond rapidly to bacterial infection. A key cellular
      component of the innate immune response is the neutrophil, whose cytoplasmic
      granules contain a variety of antimicrobial proteins and peptides. Among these is
      the bactericidal/permeability-increasing protein (BPI), a cationic 55 kDa protein
      whose selective anti-infective action against Gram-negative bacteria is based on
      its high (nM) affinity for lipopolysaccharide (LPS, or "endotoxin"). Binding of
      BPI to Gram-negative bacteria results in growth inhibition, serves as an opsonin
      that enhances phagocytosis of bacteria and inhibits bacteria-induced inflammatory
      responses by blocking the interaction of LPS with host pro-inflammatory pathways.
      Expression of BPI appears to be developmentally regulated as human newborns
      apparently have lower neutrophil BPI levels than adults. BPI expression has also
      recently been demonstrated in human epithelial cells where it appears to be
      inducible by endogenous anti-inflammatory lipids (lipoxins). BPI's potent anti
      endotoxic activity against a broad range of Gram-negative bacterial pathogens is
      manifest in biological fluids and renders it an attractive template for
      pharmaceutical development. Indeed, rBPI(21), an active recombinant protein
      derived from human BPI, has proven safe in Phase I human trials, shown promise in
      Phase II trials and has recently completed a Phase III trial for severe
      meningococcaemia with apparent benefit. Identification and evaluation of
      additional disease entities characterised by Gram-negative bacteraemia and/or
      endotoxaemia as possible targets for BPI therapy continues.

PMID- 11829711
TI  - Evolving therapies for the treatment of chronic hepatitis B virus infection.
AB  - Despite the availability of prophylactic vaccines lamivudine and IFN-alpha,
      chronic hepatitis B remains an enormous global health problem. Several promising
      nucleosides/nucleotides are undergoing clinical trials, including adefovir
      dipivoxil, the latter of which is active against lamivudine-resistant hepatitis B
      virus (HBV). In addition to nucleosides/nucleotides, it will be important to
      develop new agents with different modes of action. Novel small molecule
      inhibitors, as well as gene therapy approaches, have produced encouraging results
      in vitro and in animal models. Additional immunomodulatory therapies, including
      thymosin-alpha 1, IL-12 and several therapeutic vaccines, are also being
      explored. Combination therapy with multiple nucleosides/nucleotides and other
      agents will play an important role in the treatment of hepatitis and may help
      achieve complete viral suppression, host-mediated elimination of infected cells
      and lasting immunity.

PMID- 11829712
TI  - The macrolides.
AB  - Erythromycin, which was introduced over 50 years ago, was the first macrolide to
      be used clinically. "New" macrolides, for the treatment of patients with various
      infectious diseases, were not clinically introduced until 40 years later. The
      pharmacokinetic and adverse events profile of erythromycin initially limited its
      use to an alternative agent for patients with allergy to beta-lactam agents.
      However, the emergence of atypical and/or new pathogens and the ongoing
      escalation of acquired antimicrobial resistance has impacted on the empirical and
      organism directed therapy of infectious diseases. Azithromycin and clarithromycin
      were developed by enhancing the basic macrolide structure. Some of the basic
      features associated with these new agents include a pharmacokinetic profiles that
      allow once or twice daily dosing with a much lower incidence of side effects and
      a substantially broader spectrum of activity which includes some Gram-negative
      bacilli, atypical pathogens and new, unconventional or uncommon pathogens.
      Clinical trial data has supported the use of "new" macrolides in a wide range of
      clinical indications, however, some specific indications are currently restricted
      to treatment with either azithromycin or clarithromycin. Macrolide resistance is
      a class effect and depending on the mechanism will confer either low or high
      level resistance. While resistance is problematic, it does not always result in
      clinical failure. The macrolides are a valuable class of antimicrobial agent and
      play an important role in the management of infectious diseases.

PMID- 11829713
TI  - The therapeutic potential of inhibitors of the trypanothione cycle.
AB  - There is an urgent need for new drugs in the treatment of human African
      trypanosomiasis, Chagas' disease and leishmaniasis. This article provides an
      overview of current drugs, formulations and their deficiencies. Targets for the
      design of new drugs and the rational provided for targeting enzymes of the
      trypanothione cycle are described. Biochemical aspects of the cycle and the
      currently investigated target trypanothione reductase are discussed as are the
      several classes of inhibitors and their in vitro potencies. Evidence is provided
      for considering the tryparedoxins as a new target for antiprotozoal chemotherapy
      and a summary of glutathione-based inhibitors with significant in vitro activity
      is reported.

PMID- 11829714
TI  - Fluoroquinolones and tuberculosis.
AB  - Tuberculosis (TB) remains one of the main causes of morbidity worldwide, and the
      emergence of multi-drug resistant (MDR) Mycobacterium tuberculosis strains in
      some parts of the world has become a major concern. The decrease in activity of
      the major anti-TB drugs, such as isoniazid and rifampicin, is an important threat
      and alternative therapies are urgently required. The anti-TB activity of the
      fluoroquinolones has been under investigation since the 1980s. Many are active in
      vitro but only a few, including ofloxacin, ciprofloxacin, sparfloxacin,
      levofloxacin and lomefloxacin, have been clinically tested. Fluoroquinolones can
      be used in co-therapy with the available anti-TB drugs. However, the choice of
      fluoroquinolone should be based not only on the in vitro activity, but also on
      the long-term tolerance. Fluoroquinolones are novel anti-TB drugs to be used when
      a patient is infected with a MDR-TB strain.

PMID- 11829715
TI  - Antihistamines in late-phase clinical development for allergic disease.
AB  - Allergic rhinitis (AR) is a global health concern and shares a high comorbidity
      with asthma. Recent research suggests that different allergic diseases, such as
      AR, asthma, allergic conjunctivitis and chronic idiopathic urticaria (CIU), are
      evoked by common pathological mechanisms characterised by the release of
      histamine and other inflammatory mediators. Although H(1) receptor antagonists
      are the mainstay of therapy for allergic disease, the unacceptably high incidence
      of anticholinergic and CNS-related side effects of first-generation H(1)
      antagonists led to the search for improved second-generation H(1) antagonists.
      While many of these agents were largely devoid of CNS side effects, their
      tendency for drug-drug interactions (e.g., terfenadine and astemizole) resulted
      in an increased incidence of cardiotoxicity. Furthermore, second-generation H(1)
      antagonists exhibited weak anti-inflammatory properties and had no effect on
      nasal congestion. These observations emphasised the need for newer anti-allergic
      agents with a broader spectrum of activity and an improved safety profile. Among
      the newer H(1) antagonists currently in clinical development, desloratadine and
      mizolastine are the most widely studied. Both have a rapid onset of action, and
      desloratadine has demonstrated clinical efficacy in AR, CIU and seasonal asthma.
      Desloratadine has several advantages over other H(1) antagonists in that it has
      proven decongestant activity, a sparing effect on the use of bronchodilators
      (beta(2)-agonists) and a low potential for drug interactions. The broad anti
      inflammatory properties of desloratadine and mizolastine, which distinguish these
      agents from other H(1) antagonists in clinical development (e.g., norastemizole
      and levocetirizine), suggest they may have a more profound impact on the
      underlying disease in patients suffering from different forms of allergy. The
      lack of clinical efficacy and safety data on rupatadine and HSR-609, both novel
      H(1) antagonists, precludes an accurate assessment of their potential for
      treating allergic disease. Epinastine and efletirizine are being developed
      exclusively for topical application and are unlikely to play a significant role
      in the management of allergic diseases as a whole.

PMID- 11829716
TI  - Therapeutic potential of thromboxane inhibitors in asthma.
AB  - This paper reviews the role of thromboxane A(2) (TXA(2)) in the pathogenesis of
      pulmonary allergies, particularly asthma. The potential of TXA(2) modifiers in
      the prevention and/or treatment of pulmonary allergies is also discussed.
      Bronchial asthma is characterised by reversible airway obstruction, bronchial
      hyperresponsiveness and inflammation. Several studies have elucidated the role of
      arachidonic acid metabolites (leukotrienes, prostaglandins and TXA(2)) in the
      pathogenesis of asthma. Among those mediators, TXA(2) has attracted attention due
      to its strong physiological activity. Indeed, TXA(2) demonstrates not only potent
      bronchoconstrictive activity but is also believed to be involved both in late
      asthmatic responses and in bronchial hyperresponsiveness, a typical feature of
      this disease. Several thromboxane receptor antagonists (TXRAs) and thromboxane
      synthase inhibitors (TXSIs) have been studied with the aim of reducing or
      preventing asthma. As double-blind, placebo-controlled clinical trials have
      proven the efficiency of some TXA(2) modifiers in treating asthma, the TP
      receptor antagonist seratrodast (AA-2414) and the thromboxane synthase inhibitor
      ozagrel hydrochloride (OKY-046) are now available as anti-asthmatic agents in
      Japan. Moreover, seratrodast and ramatroban (BAY-U-3405), another thromboxane
      receptor antagonist, are currently under Phase III clinical evaluation in the US
      for the treatment of asthma.

PMID- 11829717
TI  - Combination of dexamethasone and a somatostatin analogue in the treatment of
      advanced prostate cancer.
AB  - The local microenvironment at the sites of cancer metastases protects tumour
      cells from anticancer drug-induced apoptosis via mechanisms, such as soluble
      growth factors and cytokines. The concept of antisurvival factor (ASF) therapy as
      a component of anticancer treatments aims at neutralising the protective effect
      conferred upon cancer cells by the survival factor(s) derived by the local
      microenvironment, in order to enhance the sensitivity and/or reverse the
      resistance of tumour cells to other anticancer therapeutic strategies. Herein, we
      review the translation of this concept from ex vivo studies to clinical
      applications in the setting of prostate cancer refractory to androgen ablation
      (stage D3). At this stage, which predominantly involves bone metastases, insulin
      like growth factor 1 (IGF-1) production (either growth hormone (GH)-dependent or
      GH-independent) can protect tumour cells from apoptosis, despite the significant
      suppression of androgens. The application of the ASF therapeutic concept involves
      the combination of dexamethasone (which suppresses GH-independent IGF-1) and
      somatostatin analogue (which suppresses endocrine, GH-dependent IGF-1) with the
      pro-apoptotic effect of the testicular androgen suppression by sustained use of
      LHRH analogues. In stage D3, patients who had failed anti-androgen withdrawal,
      chemotherapy and also had several other adverse prognostic features, the ASF
      based combination achieved durable objective responses and major symptomatic
      improvement, paving the way for future applications of this approach. The ASF
      based combination therapy illustrates a novel paradigm in cancer treatment: anti
      tumour treatment strategies may not only aim at directly inducing cancer cell
      apoptosis, but can also target the tumour microenvironment and neutralise the
      protection it confers on metastatic cancer cells. The favourable toxicity profile
      of this therapeutic approach calls for its testing in a randomised controlled
      setting in metastatic prostate cancer and, conceivably, in other IGF-1-responsive
      malignancies.

PMID- 11829718
TI  - Sublingual apomorphine for the treatment of erectile dysfunction.
AB  - Erectile dysfunction (ED) is a prevalent problem in the world and wreaks havoc on
      the psychosocial well-being of sufferers as well as partners. First-line
      treatment for ED is oral therapy, however, the currently available oral
      erectogenic agent is not uniformly successful and requires approximately 1 h to
      exert its effect. Apomorphine is a novel, oral erectogenic agent taken
      sublingually. It exerts its effect on hypothalamic centres involved in the
      triggering of the erection cascade. It dissolves rapidly and results in an
      erection in responders in approximately 20 min. By avoiding first pass metabolism
      through its sublingual administration, apomorphine avoids any significant
      interaction with food or other drugs. In trials in over 4000 subjects
      representative of the general ED population, beneficial effects were seen in a
      significant percentage of men. Its exact position in the market remains to be
      seen, however, its ability to permit spontaneous sexual relations will prove to
      be of significant benefit to many men.

PMID- 11829719
TI  - Fulvestrant.
AB  - Fulvestrant, a novel oestrogen receptor (ER) downregulator, is a pure anti
      oestrogen which completely blocks the trophic actions of oestrogens without
      exerting any partial agonist effects. It reduces expression of oestrogen
      receptor, progesterone receptor and proliferative and cell turnover indices. The
      drug is well-tolerated with minimal systemic side effects. Large randomised
      trials have demonstrated similar efficacy to anastrozole in the treatment of
      postmenopausal advanced breast cancer. While results of a Phase III trial
      comparing fulvestrant with tamoxifen as first-line endocrine therapy for
      postmenopausal advanced breast cancer are awaited, future studies on its role in
      adjuvant and neoadjuvant settings, as well as in premenopausal women are
      required. With the role of tamoxifen as the gold standard of first-line therapy
      being challenged by the third generation aromatase inhibitors, direct comparison
      of the latter with fulvestrant in the first-line setting may also be worthwhile.

PMID- 11829720
TI  - Antimicrobial peptides: therapeutic potential for the treatment of Candida
      infections.
AB  - The increasing frequency of fungal infections in immunocompromised patients
      together with the emergence of strains resistant to currently used antifungal
      drugs point to an increased need for a new class of antimycotics. Antimicrobial
      peptides are promising candidates for the treatment of fungal infections since
      they have both mechanisms of action distinct from available antifungal agents and
      the ability to regulate the host immune defence systems as well. This review
      focuses on Candida albicans as a large amount of work on the mechanisms of action
      of classical antifungals as well as antimicrobial peptides, such as defensins,
      protegrins, histatins and lactoferrin (LF)-derived peptides, has been performed
      in this yeast. Analogues of these antimicrobial peptides and combinations of
      antimicrobial peptides with classical antimycotics are under investigation for
      treatment of candidiasis.

PMID- 11829721
TI  - The role of pharmacognosy in modern medicine.
AB  - Drugs of natural origin continue to be important for the treatment of many
      diseases worldwide. Pharmacognosy, a long-established pharmaceutical science, has
      played a diverse role in the discovery, characterisation, production and
      standardisation of these drugs. The relevance of this discipline in terms of
      research and teaching has increased in the last decade as members of the public
      in developed countries have turned to the use of herbal remedies for the self
      medication of minor diseases. However, many phytomedicines require further
      investigation for their clinical effectiveness, while others need to be
      thoroughly investigated for their potential health risks or interactions with
      prescription drugs.

PMID- 11829722
TI  - Salvage antiretroviral therapy in HIV infection.
AB  - Highly-active antiretroviral (ARV) therapy (HAART) has lead to a sharp decline in
      AIDS-related morbidity and mortality. Treatment failure is a common, significant
      problem and as many as 50% of patients have detectable plasma HIV RNA despite
      being on combination ARV therapy. Clinicians must be knowledgeable about the
      reasons for treatment failure and the best options available for management.
      Treatment failure can occur because of non-compliance, drug discontinuation, lack
      of drug potency, inadequate drug plasma concentration and drug resistance.
      Strategies used when selecting salvage therapy include the use of resistance
      testing to choose a regimen, the exploitation of pharmacokinetic interactions by
      boosting protease inhibitor (PI) trough levels and counselling the patient on
      compliance. When selecting the agents to use in salvage therapy, the new regimen
      should ideally include as many new agents to which no or minimal resistance is
      anticipated and at least one new class of drugs if possible. Data on salvage
      therapy mostly comes from anecdotal reports and retrospective cohort studies.
      With a paucity of clinical trial data, clinicians are often forced to prescribe
      unproven regimens based on what is anticipated about cross-resistance and drug
      interactions. It is important that new agents and new targets continue to be
      developed as an increasing number of patients in practice have exhausted all
      treatment options.

PMID- 11829723
TI  - Antifungal use in HIV infection.
AB  - Systemic fungal infections continue to be a major cause of morbidity and
      mortality among HIV-infected patients. Mucosal candidiasis remains the most
      common fungal disease in this population, while cryptococcosis and aspergillosis
      are associated with significant mortality. Histoplasmosis and penicilliosis are
      relatively common in some areas. Blastomycosis, coccidioidomycosis and
      paracoccidioidomycosis have also been described in association with HIV. Over the
      last decade, a number of clinical trials have evaluated the use of antifungal
      therapies in this population and shaped our approach to prophylaxis and therapy.
      This report outlines the state of the art in the management of HIV-associated
      fungal infections and discusses the unique difficulties and drug-drug
      interactions associated with managing fungal infections in this population.
      Deoxycholate or liposomal formulations of amphotericin B and the triazoles
      fluconazole and itraconazole are the most commonly used antifungal agents.
      Healthcare providers should be familiar with the appropriate antifungal
      management and its limitations. Possible interactions with antiretrovirals should
      be considered when prescribing antifungal treatment. An exciting new decade in
      antifungal therapy is beginning, in which the second-generation triazoles and
      echinocandins will hopefully help us to overcome the limitations of the current
      antifungal arsenal.

PMID- 11829725
TI  - Azithromycin for the treatment and control of trachoma.
AB  - Trachoma, a recurrent follicular conjunctivitis caused by Chlamydia trachomatis,
      is the leading cause of preventable blindness worldwide. Efforts to control this
      disease have met with limited success. This failure is due in part to the
      limitations of conventional antibiotic treatment, a prolonged course of topical
      tetracycline. Azithromycin, an azalide antibiotic, is effective against
      chlamydial infections when given as a single oral dose. Recent research from
      Africa has shown azithromycin to be as effective as tetracycline in the treatment
      of trachoma. Under operational conditions azithromycin proved to be more
      effective. This success is attributed to a much-improved compliance with
      treatment. Community-wide mass treatment with azithromycin is advocated as a
      means of controlling trachoma in endemic countries. Questions still remain over
      the use of azithromycin for this purpose. The frequency and target population of
      mass distribution campaigns need to be defined. A few countries are beneficiaries
      of a philanthropic donation by the manufacturer of azithromycin, Pfizer Inc.
      However, in the absence of a drug donation programme the cost-effectiveness of
      this measure is unclear.

PMID- 11829724
TI  - Neuraminidase inhibitors for the treatment and prevention of influenza.
AB  - The impact of influenza virus infection is estimated to run into billions of
      dollars worldwide. Vaccination plays a key role in prevention; however, vaccines
      do not provide complete protection against influenza due to the constant mutation
      of the virus responsible. Unlike amantadine and rimantadine, which are only
      effective against influenza A, the new neuraminidase inhibitors zanamivir
      (Relenza), GlaxoSmithKline) and oseltamivir (Tamiflu), Gilead/Roche) are potent
      and specific inhibitors of influenza types A and B and have minimal side effects.
      The greatest benefit is derived if treatment commences as soon as possible after
      symptoms develop. In order for these inhibitors to have a significant impact on
      the disease, clinicians and the general public need to be made more aware of the
      symptoms of influenza and the availability of these new drugs.

PMID- 11829726
TI  - Current pharmacotherapy of pneumococcal meningitis.
AB  - Streptococcus pneumoniae is the leading cause of bacterial meningitis for people
      of all age groups after infancy. Prior to the emergence of penicillin-resistant
      pneumococci as the cause of meningitis, penicillin was the traditional therapy
      for this life-threatening infection. Treatment guidelines for both suspected and
      confirmed cases of pneumococcal meningitis (PM) have had to evolve in response to
      the phenomenon of increasing antibiotic resistance. In addition, research efforts
      have attempted to clarify the role of dexamethasone and the importance of prompt
      antibiotic therapy in the management of patients with PM. This article provides a
      review of general therapeutic principles, current treatment guidelines and
      alternative therapeutic choices for patients with PM.

PMID- 11829727
TI  - Treatment and prevention of infective endocarditis.
AB  - The paper presents the most recent recommendations for the treatment and
      prevention of infective endocarditis (IE). The treatment of IE is complex and
      requires close collaboration among specialists in infectious diseases,
      cardiology, cardiac surgery and microbiology. The mainstay of medical treatment
      is antibiotic therapy. Theoretical considerations regarding vegetations and
      antibiotics have practical consequences on the route and modalities of
      administration of antibiotics and on the techniques used to monitor treatment.
      The choice of antibiotics depends on the microorganism (streptococci,
      enterococci, staphylococci, HACEK group [Haemophilus sp., Actinobacillus sp.,
      Cardiobacterium sp., Eikenella sp. and Kingella sp.], Coxiella, Brucella,
      Legionella, Bartonella, fungi) and on whether IE occurs on native or prosthetic
      valves. Treatment of IE with negative blood cultures is particularly difficult.
      Cardiac surgery is often needed during the bacteriologically active period (in
      ~50% of patients). The decision to intervene and the optimal timing of the
      intervention requires careful consideration of multiple potential risks: the
      haemodynamic risk, the infectious risk, the risk due to cardiac lesions, the risk
      due to extracardiac complications and the risk due to the location of infective
      endocarditis. Even though the efficacy of antibiotic prophylaxis of IE is not
      completely proven, it is recommended for selected patients who undergo an at-risk
      procedure. Lists of cardiac conditions and of medical procedures at risk are
      presented; specific antibiotic prophylactic regimens for dental and upper
      respiratory tract procedures in out-patients, procedures under general
      anaesthesia and urological and GI procedures are outlined.

PMID- 11829728
TI  - Current concepts in the management of gonorrhoea.
AB  - The incidence of gonorrhoea is again rising in developed countries and a high
      disease rate has been maintained in less developed regions for a number of years.
      The need not only for treatment of the individual but also for control of
      gonorrhoea at a community level has increased significantly following recognition
      of its role in the amplification of human immunodeficiency virus (HIV)
      transmission. A sustainable decrease in the incidence of gonorrhoea and other
      sexually transmitted diseases (STDs) requires an integrated approach combining
      improved prevention, better diagnosis and optimal treatment. Effective antibiotic
      treatment is an essential element of this approach. However, antibiotic treatment
      of gonorrhoea has been severely hampered by the development of antibiotic
      resistance in Neisseria gonorrhoeae, to the extent that many therapies are no
      longer effective. Those treatments that retain acceptable efficacy are often
      unaffordable where they are most needed. Penicillins and tetracyclines should no
      longer be used in gonococcal disease, there are limitations on the effectiveness
      of newer macrolides and spectinomycin and in many parts of the world quinolones
      have been withdrawn from schedules for the treatment of gonorrhoea. Of all the
      current agents used to treat all forms of gonococcal disease, only the third
      generation cephalosporins (most notably ceftriaxone) have retained their
      efficacy; however, decreased susceptibility to these antibiotics has also
      appeared. Continuing reliance on antibiotic treatment for controlling gonorrhoea
      in the absence of other necessary approaches will see a further deterioration in
      the situation. In these circumstances the possibility that gonorrhoea will be
      untreatable becomes more real.

PMID- 11829729
TI  - Medical management of primary pulmonary hypertension.
AB  - Primary pulmonary hypertension (PPH) is a rare disease effecting the pulmonary
      vasculature. Patients present with dyspnoea on exertion, chest pain, near syncope
      and evidence of right heart failure. The natural history of PPH was described in
      the 1980s and the survival rate was quite poor. The introduction of iv.
      epoprostenol in the early 1990s has significantly altered the natural history of
      this disease. Due to the complicated nature of this therapy, inhaled, sc. and
      oral prostacyclins have also been evaluated for treatment of PPH. The most recent
      class of medications added to the armamentarium for the treatment of PPH are the
      endothelin receptor antagonists. This paper reviews the available therapies for
      the treatment of PPH.

PMID- 11829730
TI  - The use of alpha-adrenoceptor antagonists in lower urinary tract disease.
AB  - alpha-adrenoceptor antagonists have traditionally been used in the treatment of
      hypertension but in recent years they have become increasingly common in the
      treatment of benign prostatic enlargement (BPE), where they reduce the 'dynamic'
      component of bladder outlet obstruction and appear to have additional actions to
      reduce irritative symptoms of the disease. Prazosin (Hypovase), Alza), doxazosin
      (Cardura), Pfizer), indoramin (Doralese), Wyeth-Ayerst Pharmaceuticals Inc.) and
      terazosin (Hytrin), Abbott Laboratories) are currently available in the UK for
      BPE but these agents have cardiovascular actions in a significant number of
      patients, inducing effects which must be considered adverse unless the patient
      also requires treatment for mild-to-moderate hypertension. The uroselective alpha
      adrenoceptor antagonists tamsulosin (Flomax), Yamanouchi Pharmaceutical Co. Ltd.)
      and alfuzosin (Xatral), Sanofi-Synthelabo) have recently been introduced. These
      agents exert their selectivity via different mechanisms; selective tissue
      distribution for alfuzosin and alpha-adrenoceptor subtype selectivity for
      tamsulosin. The incidence of cardiovascular side effects for both drugs is
      similar to placebo. Several lines of evidence suggest that the alpha-adrenoceptor
      antagonists may relieve lower urinary tract (LUT) symptoms by other mechanisms
      additional to those which account for the reduction in bladder outlet
      obstruction. If correct, these agents may be of use in the treatment of other
      bladder conditions.

PMID- 11829731
TI  - Reviparin sodium - a new low molecular weight heparin.
AB  - Reviparin sodium (Clivarine), Knoll AG) is a low molecular weight heparin (LMWH)
      with a mean peak molecular weight of 3900 Da. It is characterised by a narrow
      molecular weight distribution profile, with an anti-factor Xa (anti-Xa):anti
      factor IIa (anti-IIa) ratio of >or=3.6. In healthy human volunteers, plasma anti
      Xa activity was up to five times higher and lasted three times longer with
      reviparin compared with unfractionated heparin (UFH). Unlike UFH, reviparin has
      negligible effects on global clotting tests. Reviparin has been shown to be as
      effective as UFH in different prophylactic indications and causes fewer injection
      site haematomas. At a daily dose of 1750 IU anti-Xa it was as effective as UFH in
      preventing deep vein thrombosis (DVT) in moderate risk surgery (general and
      abdominal) and significantly reduced DVT in patients with brace immobilisation of
      the legs. At a daily dose of 4200 IU anti-Xa reviparin was as effective as UFH or
      enoxaparin in preventing DVT in high risk orthopaedic surgery and as effective as
      UFH in prevention of DVT and/or pulmonary embolism (PE) and/or mortality in high
      risk orthopaedic surgery. In patients with acute venous thromboembolism (VTE),
      reviparin was more effective than UFH in thrombus reduction and at least as
      effective as UFH in the prevention of clinical recurrence of DVT and/or PE. The
      use of reviparin is associated with a similar or lower incidence of bleeding
      complications than UFH.

PMID- 11829732
TI  - Insulin aspart: promising early results borne out in clinical practice.
AB  - The novel, rapid-acting insulin analogue insulin aspart (IAsp; Novo Nordisk) has
      been shown in preclinical studies to be more rapidly absorbed than human insulin
      (HI) when administered subcutaneously. IAsp reaches higher peak serum
      concentrations in a shorter time than HI, whilst maintaining a similar receptor
      binding and safety profile. The physiological pharmacokinetic profile of IAsp
      compared to that of HI has been demonstrated in both adult and paediatric
      populations and was accompanied by small but statistically significant reductions
      in HbA(1c), lower postprandial glucose excursions and a reduced risk of late
      postprandial and major nocturnal hypoglycaemia. Benefits may be maximised by dose
      optimisation, using bolus doses that result in effective postprandial glucose
      reduction, as well as higher and multiple basal insulin doses. The safety
      profile, including cardiovascular risk, is equivalent to HI.

PMID- 11829733
TI  - A review of pramipexole and its clinical utility in Parkinson's disease.
AB  - Parkinson's disease (PD) is a common neurodegenerative disorder characterised by
      selective loss of dopaminergic neurones in the substantia nigra and resulting in
      progressive disability. Therapy has focused on replacing depleted dopamine (DA)
      via supplementation with levodopa or DA agonists. Pramipexole (Mirapex),
      Pharmacia Corp.) has recently been approved for the treatment of PD. Evidence
      from preclinical studies and clinical trials have proven the effectiveness of
      this agent in ameliorating the symptoms of PD. There is also non-human evidence
      that pramipexole may be neuroprotective and could therefore possibly slow disease
      progression; however, this has yet to be proven in humans. The use of pramipexole
      may be limited by its side effect profile compared to standard therapies and its
      relatively higher cost compared to levodopa. Despite these concerns, pramipexole
      does have a role in the treatment of PD in all stages of the illness and may
      arguably be the treatment of choice in early disease. In addition to its use in
      PD, pramipexole has shown some utility in the treatment of restless legs syndrome
      (RLS), depression and schizophrenia.

PMID- 11829735
TI  - Reciprocal regulation of capacitative and non-capacitative Ca2+ entry in A7r5
      vascular smooth muscle cells: only the latter operates during receptor
      activation.
AB  - In A7r5 vascular smooth muscle cells, Arg(8)-vasopressin (AVP) stimulates
      phospholipase C leading to activation of two distinct Ca(2+) entry pathways. The
      capacitative Ca(2+) entry (CCE) pathway is activated by depletion of Ca(2+)
      stores, is permeable to Mn(2+), Ba(2+) and Ca(2+), and is selectively blocked by
      Gd(3+)(1 microM). A7r5 cells also express a non-capacitative Ca(2+) entry (NCCE)
      pathway, which is activated by arachidonic acid that is released by the
      sequential activities of phospholipase C and diacylglycerol lipase. This pathway
      is permeable to Sr(2+), Ba(2+) and Ca(2+) and selectively blocked by (R,S)-(3,4
      dihydro-6,7-dimethoxy-isochinolin-1-yl)-2-phenyl-N,N-di[2-(2,3,4
      trimethoxyphenyl)ethyl]acetamid mesylate ("LOE-908"). We use these selective
      tools to show that AVP, via the same signalling pathway that leads to activation
      of NCCE, also inhibits CCE and that the inhibition is not due to depolarization
      of the plasma membrane. Using the selective inhibitors to resolve the
      contributions of each Ca(2+) entry pathway during stimulation with AVP, we
      establish that reciprocal regulation of CCE and NCCE by arachidonic acid ensures
      that only NCCE is active in the presence of AVP, whereas CCE is active only after
      its removal. NCCE and CCE are therefore activated in a strict temporal sequence:
      NCCE first and then CCE. Because Ca(2+) passing through different Ca(2+) entry
      pathways can selectively regulate different responses, reciprocal regulation of
      CCE and NCCE may allow a stimulus to first evoke a response and then recruit
      actively a different response when the stimulus is removed.

PMID- 11829734
TI  - Cross-talk unfolded: MARCKS proteins.
AB  - The proteins of the MARCKS (myristoylated alanine-rich C kinase substrate) family
      were first identified as prominent substrates of protein kinase C (PKC). Since
      then, these proteins have been implicated in the regulation of brain development
      and postnatal survival, cellular migration and adhesion, as well as endo-, exo-
      and phago-cytosis, and neurosecretion. The effector domain of MARCKS proteins is
      phosphorylated by PKC, binds to calmodulin and contributes to membrane binding.
      This multitude of mutually exclusive interactions allows cross-talk between the
      signal transduction pathways involving PKC and calmodulin. This review focuses on
      recent, mostly biophysical and biochemical results renewing interest in this
      protein family. MARCKS membrane binding is now understood at the molecular level.
      From a structural point of view, there is a consensus emerging that MARCKS
      proteins are "natively unfolded". Interestingly, domains similar to the effector
      domain have been discovered in other proteins. Furthermore, since the effector
      domain enhances the polymerization of actin in vitro, MARCKS proteins have been
      proposed to mediate regulation of the actin cytoskeleton. However, the recent
      observations that MARCKS might serve to sequester phosphatidylinositol 4,5
      bisphosphate in the plasma membrane of unstimulated cells suggest an alternative
      model for the control of the actin cytoskeleton. While myristoylation is
      classically considered to be a co-translational, irreversible event, new reports
      on MARCKS proteins suggest a more dynamic picture of this protein modification.
      Finally, studies with mice lacking MARCKS proteins have investigated the
      functions of these proteins during embryonic development in the intact organism.

PMID- 11829737
TI  - Role of Rac and Cdc42 in lysophosphatidic acid-mediated cyclo-oxygenase-2 gene
      expression.
AB  - The role of Rho proteins in lysophosphatidic acid (LPA)-mediated induction of
      cyclo-oxygenase-2 (Cox-2) was investigated in renal mesangial cells. Previous
      studies had shown that toxin B, an inhibitor of Rho, Rac and Cdc42, suppressed
      Cox-2 induction. A role for RhoA in pertussis toxin-sensitive LPA signalling was
      excluded with C3 transferase from Clostridium limosum, used as the fusion toxin
      C2IN-C3 (where C2IN is part of the C2I toxin of C. botulinum). Incubation of the
      cells with C2IN-C3 disrupted cytosolic actin stress fibres, but had no effect on
      Cox-2 induction. Similarly, activation of p42/44 mitogen-activated protein kinase
      (MAP kinase), an upstream step in Cox-2 induction, was inhibited by toxin B, but
      not affected by C2IN-C3. Upon treatment with toxin B, focal adhesion kinase and
      paxillin were dephosphorylated at tyrosine residues and the actin cytoskeleton
      was completely destroyed. An intact cytoskeleton, however, was not required for
      p42/44 MAP-kinase activation or Cox-2 induction, as shown by the actin
      depolymerizing agent cytochalasin D. Toxin B did not influence functionality of
      LPA receptors, because G(i)-mediated Ca(2+) release from intracellular stores
      remained unchanged. Within 1 h, toxin B inactivated and translocated RhoA and
      Cdc42 to the cellular membranes. Within the same time frame, monoglucosylated
      Rac1 was degraded. Direct stimulation of Rho proteins by cytotoxic necrotizing
      factor type 1 (CNF1) induced Cox-2 expression, which was sensitive to inhibition
      of the MAP-kinase pathway by PD98059, but not to an inhibitor of RhoA kinase. By
      exclusion of RhoA and non-specific cytoskeletal effects, the results in the
      present study indicate an important role for Rac and/or Cdc42 in pertussis toxin
      sensitive LPA-mediated Cox-2 induction.

PMID- 11829736
TI  - Inhibition of mitochondrial calcium-independent phospholipase A2 (iPLA2)
      attenuates mitochondrial phospholipid loss and is cardioprotective.
AB  - Calcium-independent phospholipase A(2) (iPLA(2)) is the predominant phospholipase
      A(2) present in myocardium, and its pathophysiological role in acute myocardial
      infarction has been suggested by the rapid increase in membrane-associated
      iPLA(2) activity during myocardial ischaemia and reperfusion (I/R). We therefore
      examined iPLA(2) in mitochondrial fractions prepared from Langendorff-perfused
      adult rabbit hearts. Our studies indicate that iPLA(2)beta is present in rabbit
      heart mitochondrial inner membranes with no apparent translocation during
      ischaemia, I/R or preconditioning. Mitochondrion-associated iPLA(2) was
      catalytically competent and exhibited 2-, 3- and 2.5-fold increases in measured
      iPLA(2) activity following ischaemia, I/R and preconditioning, respectively, when
      compared with the activity of iPLA(2) measured in mitochondria from control
      hearts. Mitochondrial phospholipids are essential for maintaining the ordered
      structure and function of the organelle. I/R resulted in a rapid overall decrease
      in phosphatidylcholine and phosphatidylethanolamine glycerophospholipid species,
      as determined by electrospray ionization MS, that was partially alleviated by
      pretreatment of hearts with the iPLA(2)-specific inhibitor, bromoenol lactone
      (BEL). Pretreatment of I/R hearts with 10 microM BEL significantly reduced the
      infarct size almost to that of continuously perfused hearts and was
      cardioprotective only when administered prior to ischaemia. Cardioprotection by
      BEL was reversed by the simultaneous perfusion of 100 microM 5-hydroxydecanoate,
      implicating the mitochondrial K(ATP) channel in BEL-mediated protection from I/R.
      Preconditioning also significantly reduced the infarct size in response to I/R
      but protection was lost by concurrent perfusion of 10 microM arachidonic acid.
      Taken together, these data strongly implicate mitochondria-associated iPLA(2) in
      the signal transduction of myocardial I/R injury.

PMID- 11829738
TI  - Structural and functional characterization of the human and mouse fibulin-1 gene
      promoters: role of Sp1 and Sp3.
AB  - Fibulin-1 is a multifunctional extracellular protein involved in diverse
      biological processes including cardiovascular development, haemostasis and
      cancer. To investigate the transcriptional regulation of the gene encoding
      fibulin-1 we cloned and analysed about 4.0 kb of the 5'-flanking regions of both
      the human and mouse fibulin-1 genes. The human and mouse fibulin-1 promoters
      share little sequence similarity except for a short region of approx. 150-170 bp
      immediately upstream of the translation start site. The conserved region contains
      a TATA-like sequence (ATAATT) and multiple consensus binding sites for Sp1 and
      activator protein 2 (AP-2). That the short conserved region in each gene confers
      basal promoter activity is demonstrated by transient transfections of promoter
      deletion constructs for both the human and mouse genes into cells that express
      fibulin-1 constitutively. Co-transfections of promoter constructs with expression
      plasmids for Sp1, Sp3 and Sp4 into Drosophila SL2 cells indicate that Sp1 and Sp3
      are essential for transcriptional activation and that these two factors act
      synergistically. Electrophoretic mobility-shift assays show that Sp1 and Sp3, but
      not AP-2, bind to the basal promoter of the human fibulin-1 gene. The results
      demonstrate the functional importance of Sp1 and Sp3 in regulating the expression
      of the fibulin-1 gene.

PMID- 11829739
TI  - Induction of glutathione synthesis by oxidized low-density lipoprotein and 1
      palmitoyl-2-arachidonyl phosphatidylcholine: protection against quinone-mediated
      oxidative stress.
AB  - Exposure of endothelial cells to oxidized low-density lipoprotein (oxLDL) leads
      to diverse cellular effects, including induction of the intracellular antioxidant
      GSH. It is not known whether lipid-or protein-derived oxidation products cause
      GSH induction and whether this involves increased activity of the key enzyme in
      its synthesis, glutamate-cysteine ligase (GCL). Furthermore, the effect of oxLDL
      exposure on the cell's ability to combat oxidative stress has not been previously
      examined. In the present study we found that, in bovine aortic endothelial cells,
      LDL or 1-palmitoyl-2-arachidonyl phosphatidylcholine oxidized by different
      reactive oxygen and nitrogen species induced GSH synthesis. However, prevention
      of GSH synthesis during exposure to oxLDL caused extensive cell death. The
      mediator causing GSH induction was shown to be a polar lipid and resulted in the
      increased activity of GCL as well as increased protein levels of the regulatory
      subunit of GCL. Pretreatment with both oxLDL and the polar lipid subfraction of
      the oxLDL protected cells against the toxicity of 2,3-dimethoxynaphthoquinone
      (DMNQ), a superoxide- and H(2)O(2)-forming compound. The potential of a low level
      of lipid peroxidation products to initiate cytoprotective pathways are discussed.

PMID- 11829740
TI  - Phytanic acid, a novel activator of uncoupling protein-1 gene transcription and
      brown adipocyte differentiation.
AB  - Phytanic acid (3,7,11,15-tetramethylhexadecanoic acid) is a phytol-derived
      branched-chain fatty acid present in dietary products. Phytanic acid increased
      uncoupling protein-1 (UCP1) mRNA expression in brown adipocytes differentiated in
      culture. Phytanic acid induced the expression of the UCP1 gene promoter, which
      was enhanced by co-transfection with a retinoid X receptor (RXR) expression
      vector but not with other expression vectors driving peroxisome proliferator
      activated receptor (PPAR)alpha, PPARgamma or a form of RXR devoid of ligand
      dependent sensitivity. The effect of phytanic acid on the UCP1 gene required the
      5' enhancer region of the gene and the effects of phytanic acid were mediated in
      an additive manner by three binding sites for RXR. Moreover, phytanic acid
      activates brown adipocyte differentiation: long-term exposure of brown
      preadipocytes to phytanic acid promoted the acquisition of the brown adipocyte
      morphology and caused a co-ordinate induction of the mRNAs for gene markers of
      brown adipocyte differentiation, such as UCP1, adipocyte lipid-binding protein
      aP2, lipoprotein lipase, the glucose transporter GLUT4 or subunit II of
      cytochrome c oxidase. In conclusion, phytanic acid is a natural product of phytol
      metabolism that activates brown adipocyte thermogenic function. It constitutes a
      potential nutritional signal linking dietary status to adaptive thermogenesis.

PMID- 11829741
TI  - A dominant-negative isoform lacking exons 11 and 12 of the human hypoxia
      inducible factor-1alpha gene.
AB  - Hypoxia-inducible factor-1alpha (HIF-1alpha), a member of the transcription
      family characterized by a basic helix-loop-helix (bHLH) domain and a PAS domain,
      regulates the transcription of hypoxia-inducible genes involved in
      erythropoiesis, vascular remodelling and glucose/energy metabolism. It contains
      bHLH/PAS domains in the N-terminal half, and a nuclear localization signal (NLS)
      and two transactivation domains (TADs) in the C-terminal half. It also has an
      oxygen-dependent degradation (ODD) domain, which is required to degrade HIF
      1alpha protein by the ubiquitin-proteasome pathway. In this study, we identified
      a new alternatively spliced variant of human HIF-1alpha mRNA, which lacked both
      exons 11 and 12, producing a frame shift and giving a shorter form of HIF-1alpha.
      In the corresponding protein, a part of the ODD domain, both TADs and the C
      terminal NLS motif were missing. Expression of endogenous HIF-1alpha variant
      protein was identified using immunoprecipitation and immunoblotting methods. The
      expressed HIF-1alpha variant exhibited neither the activity of transactivation
      nor hypoxia-induced nuclear translocation. In contrast with HIF-1alpha, the
      variant was strikingly stable in normoxic conditions and not up-regulated to such
      an extent by hypoxia, cobalt ions or desferrioxamine. It was also demonstrated
      that the HIF-1alpha variant competed with endogenous HIF-1alpha and suppressed
      HIF-1 activity, resulting in the down-regulation of mRNA expression of hypoxia
      inducible genes. The association of the variant and arylhydrocarbon receptor
      nuclear translocator in the cytoplasm may be related to the inhibition of HIF-1
      activity. It is assumed that this isoform preserves the balance between aerobic
      and anaerobic metabolism by counteracting the overaction of HIF-1alpha.

PMID- 11829742
TI  - Lipid deprivation increases surfactant phosphatidylcholine synthesis via a sterol
      sensitive regulatory element within the CTP:phosphocholine cytidylyltransferase
      promoter.
AB  - Lipid-deprived mice increase alveolar surfactant disaturated phosphatidylcholine
      (DSPtdCho) synthesis compared with mice fed a standard diet by increasing
      expression of CTP:phosphocholine cytidylyltransferase (CCT), the rate-limiting
      enzyme for DSPtdCho synthesis. We previously observed that lipid deprivation
      increases mRNA synthesis for CCT [Ryan, McCoy, Mathur, Field and Mallampalli
      (2000) J. Lipid Res. 41, 1268-1277]. To evaluate regulatory mechanisms for this
      gene, we cloned the proximal approximately 1900 bp of the 5' flanking sequence of
      the murine CCT gene, coupled this to a luciferase reporter, and examined
      transcriptional regulation in a murine alveolar epithelial type II cell line (MLE
      12). The core promoter was localized to a region between -169 and +71 bp, which
      exhibited strong basal activity comparable with the simian virus 40 promoter. The
      full-length construct, from -1867 to +71, was induced 2-3-fold when cells were
      cultured in lipoprotein-deficient serum (LPDS), similar to the level of induction
      of the endogenous CCT gene. By deletional analysis the sterol regulatory element
      (SRE) was localized within a 240 bp region. LPDS activation of the CCT promoter
      was abolished by mutation of this SRE, and gel mobility-shift assays demonstrated
      specific binding of recombinant SRE-binding protein to this element within the
      CCT promoter. These observations indicate that sterol-regulated expression of CCT
      is mediated by an SRE within its 5' flanking region.

PMID- 11829744
TI  - Regulation of phosphatidylcholine and phosphatidylethanolamine synthesis in rat
      hepatocytes by 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR).
AB  - The present study was undertaken to study the role of AMP-activated kinase (AMPK)
      in the biosynthesis of two major membrane phospholipids, phosphatidylcholine (PC)
      and phosphatidylethanolamine (PE). Incubation of rat hepatocytes with 5
      aminoimidazole-4-carboxamide ribonucleoside (AICAR), an activator of AMPK,
      produced dose-dependent inhibition of the incorporation of [(3)H]choline and
      [(3)H]ethanolamine into PC and PE, respectively. Determination of the cellular
      uptake of choline and ethanolamine showed that the reduced synthesis of PC and PE
      did not result from impaired uptake of these two precursors. The decreased
      synthesis of PC was not mirrored by a reduction in the activities of the enzymes
      of the CDP-choline pathway. The diminution of PE biosynthesis, however, was
      paralleled by a depressed activity of CTP:phosphoethanolamine
      cytidylyltransferase (ET), the pace-setting enzyme of the CDP-ethanolamine
      pathway. AICAR treatment of hepatocytes stimulated the conversion of choline into
      betaine, indicating that reduced PC synthesis most probably resulted from a
      decrease in the availability of choline. In addition, AICAR induced a 50%
      reduction in the cellular level of diacylglycerols, which may further impair the
      synthesis of PC and PE. The results thus indicate that AICAR inhibits the
      biosynthesis of PC and PE and that the effect is exerted at different sites in
      the two pathways. Increased oxidation of choline to betaine is the main target of
      AICAR in the PC pathway, whereas inhibition of ET activity is the locus of AICAR
      action in the PE pathway.

PMID- 11829743
TI  - Active-site mutagenesis of a Lys49-phospholipase A2: biological and membrane
      disrupting activities in the absence of catalysis.
AB  - Bothropstoxin-I (BthTx-I) is a myotoxic phospholipase A(2) variant present in the
      venom of Bothrops jararacussu, in which the Asp(49) residue is replaced with a
      lysine, which damages artificial membranes by a Ca(2+)-independent mechanism.
      Wild-type BthTx-I and the mutants Lys(49)-->Asp, His(48)-->Gln and Lys(122)-->Ala
      were expressed in Escherichia coli BL21(DE3) cells, and the hydrolytic, myotoxic
      and membrane-damaging activities of the recombinant proteins were compared with
      native BthTx-I purified from whole venom. The Ca(2+)-independent membrane
      damaging and myotoxic activities of the native and wild-type recombinant BthTx-I,
      His(48)Gln and Lys(49)Asp mutants were similar; however, the Lys(122)Ala mutant
      demonstrated reduced levels of both activities. Although a low hydrolytic
      activity against a mixed phospholipid substrate was observed with native BthTx-I,
      no substrate hydrolysis was detected with the wild-type recombinant enzyme or any
      of the mutants. In the case of the Lys(49)Asp mutant, this demonstrates that the
      absence of catalytic activity in Lys(49)-PLA(2) is not a consequence of the
      single Asp(49)-->Lys replacement. Furthermore, these results provide unambiguous
      evidence that the Ca(2+)-independent membrane-damaging and myotoxic activities
      are maintained in the absence of hydrolysis. The evidence favours a model for a
      hydrolysis-independent, membrane-damaging mechanism involving an interaction of
      the C-terminal region of BthTx-I with the target membrane.

PMID- 11829745
TI  - Less hydrophobic phosphatidylcholine species simplify biliary vesicle morphology,
      but induce bile metastability with a broad spectrum of crystal forms.
AB  - Cholesterol crystallization in bile is affected by phosphatidylcholine (PtdCho)
      hydrophobicity. The aim of the present study was to determine whether PtdCho
      species modulate the metastable-labile limit and equilibrium solubility of
      cholesterol in the micellar phase of bile, thereby altering the distribution of
      cholesterol to biliary lipid carriers and thus influencing cholesterol
      crystallization. Supersaturated model bile (with a cholesterol saturation index
      of 2.0 and a total lipid concentration of 10 g/dl) was prepared with various
      PtdCho/(bile salt+PtdCho) ratios (0.1-0.5) using egg yolk or soya bean PtdCho.
      Subsequently, the following features were determined: metastable-labile limit,
      equilibrium solubility of cholesterol, metastable zone, and cholesterol
      crystallization process. Less hydrophobic PtdCho species destabilized bile
      cholesterol to induce rapid crystallization, because of a broad integrated
      metastable zone, whereas more hydrophobic species stabilized bile cholesterol
      with a less integrated metastable zone and thus retarded cholesterol
      crystallization. Cholesterol crystallization was accelerated by a decrease in the
      PtdCho/(bile salt+PtdCho) ratio, whereas the final nucleated crystal mass was
      increased by an increase in this ratio. With decreasing hydrophobicity of the
      PtdCho species, the intermixed micellar/vesicular concentration of bile salts
      decreased in association with less formation of vesicles and increased formation
      of micelles, and a variety of crystal forms were detected. In conclusion, PtdCho
      species directly influenced the cholesterol crystallization process in model bile
      by remodelling the bile mesophase, and also had an indirect influence by altering
      the balance between bile salt micelles and vesicles.

PMID- 11829746
TI  - Specific increase in leptin production in obese (falfa) rat adipose cells.
AB  - In the obese state, enlarged adipose cells display an altered gene-expression
      profile and metabolic capacity. The aim of this study was to gain insight into
      their secretory function, by assessing two secreted proteins, leptin and
      angiotensinogen, in adipose cells of obese (fa/fa) Zucker rats. A marked and co
      ordinate increase in leptin mRNA, gene transcription and promoter activity was
      observed in obese compared with lean (Fa/fa) rat adipose cells, and this resulted
      in increased leptin release in culture. Two sets of observations suggest that
      this effect is due to the fa mutation. First, adipose-cell leptin release was
      higher in heterozygous (Fa/fa) than in homozygous (Fa/Fa) lean rats. Second,
      leptin release was not enhanced in enlarged adipose cells of FalFa rats fed a
      high-fat diet for 15 days. At variance with leptin, angiotensinogen production
      was not significantly increased in the obese cells. Dexamethasone stimulated both
      leptin and angiotensinogen release in lean and obese rat adipose cells. The
      magnitude of leptin stimulation was higher in fa/fa than in Fa/fa rats, whereas
      angiotensinogen release was increased to the same extent in both genotypes. These
      observations suggest that leptin production is specifically enhanced in enlarged
      adipose cells of obese Zucker rats and that cell hypertrophy is not the sole
      determinant of this feature. Increased leptin production might be related to
      disruption of leptin signalling by the fa mutation.

PMID- 11829747
TI  - The distinct methods by which manganese and iron regulate the Nramp transporters
      in yeast.
AB  - The bakers yeast Saccharomyces cerevisiae expresses three Smf metal transport
      proteins that are differentially regulated by metal ions. Smf1p and Smf2p are
      regulated at the post-translational level by manganese, whereas Smf3p is
      regulated by iron through a mechanism that, up until now, was unknown. Through
      promoter and protein-domain swapping experiments, we now demonstrate that the
      manganese regulation of Smf1p involves an internal protein-coding region that is
      separate from the N-terminal domain of this transporter. By comparison, iron
      regulation of Smf3p involves the upstream non-coding region of the gene. Using
      SMF3-lacZ reporter constructs, we identified two distinct regions of the SMF3
      promoter that contribute to iron regulation: (1) approx. nt -435 to -350 that
      contain dual consensus recognition sites for the Aft1 iron transcription factor;
      and (2) nt -348 to -247 that do not contain obvious Aft1 binding sites. The -348
      to -247 region by itself can confer strong iron regulation to the heterologous
      CYC1 core promoter, and therefore harbours a putative upstream activating
      sequence for iron. Iron regulation of SMF3 was dramatically reduced, but not
      completely eliminated, in strains lacking both the AFT1 and AFT2 iron regulatory
      factors. Together with the promoter mapping studies, these results suggest that
      both Aft-dependent and Aft-independent pathways may contribute to iron regulation
      of SMF3.

PMID- 11829748
TI  - CD38 is the major enzyme responsible for synthesis of nicotinic acid-adenine
      dinucleotide phosphate in mammalian tissues.
AB  - In the present study, we have determined the role of the enzyme CD38 upon the
      synthesis of the Ca(2+)-releasing nucleotide nicotinic acid-adenine dinucleotide
      phosphate (NAADP). In rat tissues, we observed that the capacity for NAADP
      synthesis could be co-immunoprecipitated with CD38 using an anti-CD38 antibody.
      Furthermore, we observed that several tissues from CD38 knockout mice had no
      capacity for the synthesis of this nucleotide. In addition, CD38 was also
      identified as the major enzyme responsible for the synthesis of the second
      messenger cyclic ADP-ribose. These observations lead to the conclusion that CD38
      is the major enzyme responsible for the synthesis of NAADP and cyclic ADP-ribose,
      and raises the possibility of a new signalling pathway where two different Ca(2+)
      releasing nucleotides are synthesized by the same enzyme.

PMID- 11829749
TI  - Purification, characterization, gene cloning and preliminary X-ray data of the
      exo-inulinase from Aspergillus awamori.
AB  - Extracellular exo-inulinase has been isolated from a solid-phase culture of the
      filamentous fungus Aspergillus awamori var. 2250. The apparent molecular mass of
      the monomer enzyme was 69 +/- kDa, with a pI of 4.4 and a pH optimum of 4.5. The
      enzyme hydrolysed the beta-(2-->1)-fructan (inulin) and beta-(2-->6)-fructan
      (levan) via exo-cleavage, releasing fructose. The values for the Michaelis
      constants K(m) and V(max) in the hydrolysis of inulin were 0.003 +/- 0.0001 mM
      and 175 +/- 5 micromol.min(-1).mg(-1). The same parameters in the hydrolysis of
      levan were 2.08 +/- 0.04 mg/ml and 1.2 +/- 0.02 micromol/min per mg,
      respectively. The gene and cDNA encoding the A. awamori exo-inulinase were cloned
      and sequenced. The amino acid sequence indicated that the protein belongs to
      glycoside hydrolase family 32. A surprisingly high similarity was found to
      fructosyltransferase from Aspergillus foetidus (90.7% on the level of the amino
      acid sequence), despite the fact that the latter enzyme is unable to hydrolyse
      inulin and levan. Crystals of the native exo-inulinase were obtained and found to
      belong to the orthorhombic space group P2(1)2(1)2(1) with cell parameters
      a=64.726 A (1A=0.1 nm), b=82.041 A and c=136.075 A. Crystals diffracted beyond
      1.54 A, and useful X-ray data were collected to a resolution of 1.73 A.

PMID- 11829750
TI  - Selective determination of mitochondrial chelatable iron in viable cells with a
      new fluorescent sensor.
AB  - Mitochondrial chelatable ("redox-active") iron is considered to contribute to
      several human diseases, but has not yet been characterized in viable cells. In
      order to determine this iron pool, we synthesized a new fluorescent indicator,
      rhodamine B-[(1,10-phenanthrolin-5-yl)aminocarbonyl]benzyl ester (RPA). In a cell
      free system, RPA fluorescence was strongly and stoichiometrically quenched by
      Fe(2+). RPA selectively accumulated in the mitochondria of cultured rat
      hepatocytes. The intramitochondrial RPA fluorescence was quenched when iron was
      added to the cells in a membrane-permeant form. It increased when the
      mitochondrial chelatable iron available to the probe was experimentally decreased
      by the membrane-permeant transition metal chelators pyridoxal isonicotinoyl
      hydrazone and 1,10-phenanthroline. The concentration of mitochondrial chelatable
      iron in cultured rat hepatocytes, quantified from the increase in RPA
      fluorescence after addition of pyridoxal isonicotinoyl hydrazone, was found to be
      12.2 +/- 4.9 microM. Inhibition of haem synthesis with succinylacetone did not
      alter the signal obtained in hepatocytes, but a rapid increase in the
      concentration of mitochondrial chelatable iron was observed in human
      erythroleukaemia K562 cells. In conclusion, RPA enables the selective
      determination of the highly physiologically and pathophysiologically interesting
      mitochondrial pool of chelatable iron in intact cells and to record the time
      course of alterations of this pool.

PMID- 11829751
TI  - Polyamines are required for the initiation of rat liver regeneration.
AB  - A large number of studies applying inhibitors of polyamine biosynthesis have
      indicated that these compounds are required for animal cell proliferation. Here
      we show, using a transgenic rat model with activated polyamine catabolism, that a
      certain critical concentration of the higher polyamines spermidine and spermine
      is required for liver regeneration. Partial hepatectomy of transgenic rats
      expressing spermidine/spermine N(1)-acetyltransferase (SSAT) under the control of
      mouse metallothionein promoter strikingly induced the enzyme at 24 h and reduced
      hepatic spermidine by 80%. At that time, the weight of the liver remnant was
      significantly increased in syngenic rats and proliferating cell nuclear antigen
      (PCNA) labelling index was 20%, whereas the transgenic rats showed no liver
      weight gain and their PCNA-positive cells accounted for 0.5% of hepatocytes.
      Similarly, hepatic thymidine incorporation was markedly enhanced at this time
      point in syngenic, but not in transgenic, animals, whereas the rate of leucine
      incorporation was only marginally affected in the transgenic animals. At 3 days
      after operation, the spermidine pool in transgenic livers had increased to the
      pre-operative level, the remnant weight was significantly elevated and hepatic
      PCNA labelling index increased to 5%. N(1),N(11)-Diethylnorspermine, a powerful
      inducer of SSAT, inhibited liver weight gain and proliferative activity in both
      syngenic and transgenic rats. We found an extremely close correlation between
      hepatic spermidine, and less close between spermine, concentrations and PCNA
      labelling index during early liver regeneration. These results indicate that
      spermidine and/or spermine, but apparently not putrescine, are required for liver
      regeneration, yet at concentrations smaller than those normally found after
      partial hepatectomy.

PMID- 11829752
TI  - Stabilin-1 and -2 constitute a novel family of fasciclin-like hyaluronan receptor
      homologues.
AB  - MS-1, a high-molecular-mass protein expressed by non-continuous and angiogenic
      endothelial cells and by alternatively activated macrophages (Mphi2), and the
      hepatic sinusoidal endothelial hyaluronan clearance receptor are similar with
      respect to tissue distribution and biochemical characteristics. In the present
      study we purified these proteins by immuno- and hyaluronan-affinity
      chromatography respectively, sequenced tryptic peptides and generated full-length
      cDNA sequences in both mouse and human. The novel genes, i.e. stabilin-1 and
      stabilin-2, code for homologous transmembrane proteins featuring seven fasciclin
      like adhesion domains, 18-20 epidermal-growth-factor domains, one X-link domain
      and three to six B-(X(7))-B hyaluronan-binding motifs. Northern-blotting
      experiments revealed the presence of both stabilins in organs with predominant
      endothelial sinuses such as liver, spleen and lymph node: stabilin-1 mRNA was
      also detected in organs with predominant Mphi2 cells, such as placenta, and in
      interleukin-4/glucocorticoid-stimulated Mphi2 cells in vitro. A polyclonal
      antibody made against human recombinant stabilin-1 confirmed the expression of
      stabilin-1 protein in splenic sinus endothelial cells in vivo and in Mphi2 in
      vitro. On the basis of high similarity at the protein level and the unique domain
      composition, which differs from that of all other known fasciclin-like proteins
      and hyaluronan receptors, stabilin-1 and stabilin-2 define a novel family of
      fasciclin-like hyaluronan receptor homologues that might play a role in cell-cell
      and cell-matrix interactions in vascular function and inflammatory processes.

PMID- 11829753
TI  - Fluorescence resonance energy transfer between coumarin-derived mitochondrial
      F(1)-ATPase gamma subunit and pyrenylmaleimide-labelled fragments of IF(1) and c
      subunit.
AB  - We introduced a reporting group into a critical position of the mitochondrial
      F(1)-ATPase in order to gain structural information about enzyme-ligand
      complexes. Incubation of 7-diethylamino-3-(4'-maleimidylphenyl)-4-methylcoumarin
      (CPM) with bovine heart mitochondrial F(1)-ATPase pretreated with 1 nM sodium
      arsenite modified the only cysteine residue in the gamma subunit (gamma-Cys(78)),
      resulting in an enzyme-CPM fluorescent complex (CPM-F(1)) with an ATPase activity
      similar to that of the native enzyme. Transferred fluorescence of F(1)-bound CPM
      occurred when different peptide fragments of naturally binding polypeptides
      carrying a pyrenylmaleimide (PM) moiety were bound to the enzyme. Fluorescence
      resonance energy transfer (RET) from PM bound to cysteine residues associated
      with Glu(40), Lys(47) and Lys(58) of fragments of the inhibitor protein (IF(1))
      with CPM-F(1) occurred with an efficiency of approx. 20, 21 and 3% respectively.
      The distance at which the efficiency of energy transfer was 50%, R(0), for the
      CPM and PM donor/acceptor pair was 4.1 nm, indicating that the three IF(1)
      fragments must be within 6.7 nm of gamma-Cys(78). RET from the PM-bound
      hydrophilic fragment of c subunit (residues 37-42) of the F(1)F(0)-ATPase complex
      and CPM-bound gamma-Cys(78) occurred with an efficiency of approx. 30%,
      indicating a distance of 4.7 nm between the two fluorophores. Based on previous
      observations and on the present RET measurements, the hydrophilic loop of c
      subunit was located at the base of the F(1) foot, and the N-terminal region of
      IF(1) was located on the surface of F(1) in the lower part of the alpha(3)beta(3)
      hexamer ring.

PMID- 11829754
TI  - Mass-spectrometric analysis of agonist-induced retinoic acid receptor gamma
      conformational change.
AB  - Apo and holo forms of retinoic acid receptors, and other nuclear receptors,
      display differential sensitivity to proteolytic digestion that likely reflects
      the distinct conformational states of the free and liganded forms of the
      receptor. We have developed a method for rapid peptide mapping of holo-retinoic
      acid receptor gamma that utilizes matrix-assisted laser-desorption-ionization
      time-of-flight MS to identify peptide fragments that are derived from the
      partially proteolysed holo-receptor. The peptide maps of retinoic acid receptor
      gamma bound by four different agonists were identical, suggesting that all four
      ligands induced a similar conformational change within the ligand-binding domain
      of the receptor. In all cases, this agonist-induced conformational change
      promoted the direct association of retinoic acid receptor gamma with the
      transcriptional co-activator p300 and inhibited interaction of the receptor with
      the nuclear receptor co-repressor. SR11253, a compound previously reported to
      exert mixed retinoic acid receptor gamma agonist/antagonist activities in
      cultured cells, was found to bind directly to, but only weakly altered the
      protease-sensitivity of, the receptor and failed to promote interaction of the
      receptor with p300 or induce dissociation of receptor-nuclear receptor co
      repressor complexes. This technique should be generally applicable to other
      members of the nuclear receptor superfamily that undergo an induced structural
      alteration upon agonist or antagonist binding, DNA binding and/or protein-protein
      interaction.

PMID- 11829756
TI  - The C-terminal domain, but not the interchain disulphide, is required for the
      activity and intracellular trafficking of aminopeptidase A.
AB  - Mammalian aminopeptidase A (APA; glutamyl aminopeptidase; EC 3.4.11.7) is a type
      II membrane-spanning protein consisting of a short N-terminal cytosolic domain, a
      single transmembrane domain and a large extracellular C-terminal domain
      containing the active site. The extracellular domain consists of a 107 kDa
      domain, containing the zinc-binding motif and all the residues involved in
      catalysis, separated by a protease-susceptible hinge region from the 45 kDA C
      terminal domain of unknown function. To investigate the role of the 45 kDa
      domain, a construct of murine APA (G594Delta) lacking this C-terminal domain was
      expressed in COS-1 cells. This truncated form of APA, although expressed, lacked
      enzymic activity and failed to reach the cell surface. Confocal
      immunofluorescence microscopy revealed that G594Delta co-localized with the
      lectin concanavalin A and had a similar staining pattern as protein disulphide
      isomerase, indicating that it was retained in the endoplasmic reticulum. Thus the
      C-terminal 45 kDa domain appears to be acting like a pro-domain and seems to be
      required for the correct folding and trafficking of APA. In contrast, mutation of
      cysteine-43 to serine, which is involved in the disulphide-linkage of the APA
      homodimer, did not affect the enzymic activity, cellular location or rate of
      trafficking through the secretory pathway of APA.

PMID- 11829755
TI  - Re-evaluation of primary structure, topology, and localization of Scamper, a
      putative intracellular Ca2+ channel activated by sphingosylphosphocholine.
AB  - Naturally occurring sphingoid molecules control vital functions of the cell
      through their interaction with specific receptors. Proliferation, differentiation
      and programmed death result in fact from a fine balance of signals, among which
      sphingosine and structurally related molecules play fundamental roles, acting as
      either first or second messengers. The corresponding receptors need to be
      identified in order that the role of sphingoid molecules can be established.
      Among them, several G-protein-coupled receptors specific for sphingosine 1
      phosphate, sphingosylphosphocholine, or both, have already been investigated. In
      contrast, the identification of the postulated intracellular receptors has been
      problematical. In the present study we re-evaluated the molecular
      characterization of Scamper, the first proposed intracellular receptor for
      sphingosylphosphocholine [Mao, Kim, Almenoff, Rudner, Kearney and Kindman (1996)
      Proc. Natl. Acad. Sci. U.S.A. 93, 1993-1996] and commonly believed to be a Ca(2+)
      channel of the endoplasmic reticulum (the name "SCaMPER" used by Mao et al. being
      derived from "sphingolipid Ca(2+)-release-mediating protein of the endoplasmic
      reticulum"). In contrast with what has been believed hitherto, our primary
      structure and overexpression experiments indicate that Scamper is a 110-amino
      acid protein spanning the membrane once with a Nexo/Ccyt topology [von Heijne and
      Gavel (1988) Eur. J. Biochem. 174, 671-678]. Overexpression of either wild-type
      or tagged Scamper induces a specific phenotype characterized by the rapid
      extension of actin-containing protrusions, followed by cell death.

PMID- 11829757
TI  - Differentiation-dependent mechanisms of transcriptional regulation of the
      catalytic subunit of phosphorylase kinase.
AB  - The amount of phosphorylase kinase in skeletal muscle is exquisitely sensitive to
      developmental signals such as differentiation and innervation, and is clearly
      regulated in such a manner so as to always maintain the gamma catalytic subunit
      under the control of its regulatory alpha, beta and gamma subunits. To identify
      how the transcription of the gamma subunit is regulated, we have analysed 3.8 kb
      of the upstream regulatory region using a luciferase reporter system. A complex
      sequence of interdependent regulations is evident. The gamma catalytic subunit
      gene contains two inhibitory controls with very dominant features. Also evident
      are an array of multiple positive regulatory elements, prominent amongst which
      are four E-boxes, of which two are downstream, one is upstream and one is in the
      middle of the CAAT-TATA core promoter. Differentiation-dependent positive
      regulation arises as a consequence of both E-box regulation and the activation of
      at least one other regulatory element. The primary mode of transcriptional
      regulation of the gamma catalytic subunit gene appears to occur by the relief of
      regulation of an otherwise default inhibitory status. It is noteworthy that such
      a mode of regulation mirrors the regulation of the enzymic activity of many
      protein kinases, including phosphorylase kinase. With phosphorylase kinase, both
      its transcriptional regulation as well as the regulation of the protein itself,
      are primed to maintain the gamma catalytic subunit either unexpressed or
      inactivate respectively, until a positive signal occurs to override an otherwise
      dominant default inhibitory condition.

PMID- 11829758
TI  - Complete sequence, recombinant analysis and binding to laminins and sulphated
      ligands of the N-terminal domains of laminin alpha3B and alpha5 chains.
AB  - The N-terminal sequences of mouse laminin alpha3B and alpha5 chains have been
      completed and demonstrate the presence of a signal peptide followed by a complete
      laminin N-terminal (LN) module (domain VI). These signal peptides were released
      after recombinant production of larger fragments comprising domains VI/V (45-65
      kDa) from this region yielding properly folded proteins, which were secreted from
      HEK-293-EBNA cells. Pepsin digestion of these fragments yielded products of 25-35
      kDa, which consisted only of domain V. The alphaVI/V fragments were able to
      inhibit self-assembly of laminin-1, with those from the alpha3B and alpha5 chains
      being more active than those from alpha1 and alpha2 chains. Domain V fragments,
      however, showed a reduced activity, indicating the major contribution of the LN
      module in inhibition. These interactions were confirmed by surface-plasmon
      resonance assays demonstrating moderate affinities (K(d)=0.02 to >6 microM) for
      the binding to laminin-1. This indicated that laminins containing alpha3B or
      alpha5 chains should also be able to form non-covalent networks by
      polymerization. The LN modules also showed heparin binding in affinity
      chromatography, which was strongest for alpha1/alpha2, moderate for alpha3B,
      whereas no binding was observed for alpha5. They all bound to heparan sulphate
      chains of perlecan and to sulphatides, with a lower variability in binding
      activity. Specific antibodies were raised against alpha3BVI/V and alpha5VI/V and
      were shown to stain basement membrane zones in various mouse tissues. These
      antibodies also allowed the identification of a new laminin assembly form 5B
      consisting of alpha3B, beta3 and gamma2 chains.

PMID- 11829760
TI  - Allotopic antagonism of the non-peptide atrial natriuretic peptide (ANP)
      antagonist HS-142-1 on natriuretic peptide receptor NPR-A.
AB  - The microbial polysaccharide HS-142-1 has been documented as an antagonist of
      natriuretic peptides. It inhibits activation and peptide binding to both
      guanylate receptors natriuretic peptide receptor (NPR)-A and NPR-B, but has no
      effect on the non-cyclase receptor NPR-C. At first sight the effect of HS-142-1
      on peptide binding appears to be surmountable, suggesting that it might be
      competitive despite its chemically divergent nature. We explored its mode of
      action on wild-type NPR-A (WT), on a disulphide-bridged constitutively active
      mutant (C423S) and on truncated mutants lacking either their cytoplasmic domain
      (DeltaKC) or both the cytoplasmic and the transmembrane domains (ECD). On the WT,
      HS-142-1 inhibited atrial natriuretic peptide (ANP) binding with a pK value of
      6.51 +/- 0.07 (K(d)=0.31 microM). It displayed a similar effect on the C423S
      mutant (pK=6.31 +/- 0.11), indicating that its action might not be due to
      interference with receptor dimerization. HS-142-1 also inhibited ANP binding to
      DeltaKC with a pK of 7.05 +/- 0.05 (K(d)=0.089 microM), but it was inactive on
      ANP binding to ECD at a concentration of 10(-4) M, suggesting that the antagonism
      was not competitive at the peptide-binding site located on the ECD and that the
      transmembrane domain might be required. HS-142-1 also enhanced dissociation of
      NPR-A-bound (125)I-ANP in the presence of excess unlabelled ANP, implying an
      allotopic (allosteric) mode of action for the antagonist.

PMID- 11829759
TI  - Expression of Drosophila melanogaster xanthine dehydrogenase in Aspergillus
      nidulans and some properties of the recombinant enzyme.
AB  - Recent crystal structures of xanthine dehydrogenase, xanthine oxidase and related
      enzymes have paved the way for a detailed structural and functional analysis of
      these enzymes. One problem encountered when working with these proteins,
      especially with recombinant protein, is that the preparations tend to be
      heterogeneous, with only a fraction of the enzyme molecules being active. This is
      due to the incompleteness of post-translational modification, which for this
      protein is a complex, and incompletely understood, process involving
      incorporation of the Mo and Fe/S centres. The enzyme has been expressed
      previously in both Drosophila and insect cells using baculovirus. The insect cell
      system has been exploited by Iwasaki et al. [Iwasaki, Okamoto, Nishino, Mizushima
      and Hori (2000) J. Biochem (Tokyo) 127, 771-778], but, for the rat enzyme, yields
      a complex mixture of enzyme forms, containing around 10% of functional enzyme.
      The expression of Drosophila melanogaster xanthine dehydrogenase in Aspergillus
      nidulans is described. The purified protein has been analysed both functionally
      and spectroscopically. Its specific activity is indistinguishable from that of
      the enzyme purified from fruit flies [Doyle, Burke, Chovnick, Dutton, Whittle and
      Bray (1996) Eur. J. Biochem. 239, 782-795], and it appears to be more active than
      recombinant xanthine dehydrogenase produced with the baculovirus system. EPR
      spectra of the recombinant Drosophila enzyme are reported, including parameters
      for the Fe/S centres. Only a very weak "Fe/SIII" signal (g(1,2,3), 2.057, 1.930,
      1.858) was observed, in contrast to the strong analogous signal reported for the
      enzyme from baculovirus. Since this signal appears to be associated with
      incomplete post-translational modification, this is consistent with relatively
      more complete cofactor incorporation in the Aspergillus-produced enzyme. Thus we
      have developed a recombinant expression system for D. melanogaster xanthine
      dehydrogenase, which can be used for the production of site-specific mutations of
      this enzyme.

PMID- 11829761
TI  - Interactions of Porphyromonas gingivalis with oxyhaemoglobin and
      deoxyhaemoglobin.
AB  - When grown on blood-containing solid media, the anaerobic periodontal pathogen
      Porphyromonas gingivalis produces a haem pigment, the major component of which is
      the mu-oxo bishaem of iron protoporphyrin IX [Smalley, Silver, Marsh and Birss
      (1998) Biochem. J. 331, 681-685]. In this study, mu-oxo bishaem generation by P.
      gingivalis from oxy- and deoxyhaemoglobin was examined. Bacterial cells were
      shown to convert oxyhaemoglobin into methaemoglobin, which was degraded
      progressively, generating a mixture of both monomeric and mu-oxo dimeric iron
      protoporphyrin IX. The rate of methaemoglobin formation was accelerated in the
      presence of bacterial cells, but was inhibited by N-ethylmaleimide and tosyl
      lysylchloromethylketone. Interaction of cells with deoxyhaemoglobin resulted in
      formation of an iron(III) haem species (Soret gamma(max), 393 nm), identified as
      pure mu-oxo bishaem.

PMID- 11829762
TI  - Ceramide and sphingosine have an antagonistic effect on the plasma-membrane Ca2+
      ATPase from human erythrocytes.
AB  - The plasma-membrane Ca(2+)-ATPase is a key enzyme in the regulation of the
      intracellular Ca(2+) concentration. On the other hand, sphingolipids have been
      recognized recently as important second messengers, acting in many systems in
      combination with Ca(2+). In view of the fact that the Ca(2+)-ATPase is stimulated
      by ethanol, and since sphingolipids possess free hydroxy groups, we decided to
      study the possible effect of ceramide and sphingosine on this calcium pump. Here
      we show that ceramide stimulates the Ca(2+)-ATPase in a dose-dependent manner and
      additively to the activation observed in the presence of calmodulin or ethanol,
      when compared with any of these effectors added alone. Ceramide affects both the
      affinity for Ca(2+) and the V(max) of the enzyme. Furthermore, this second
      messenger also stimulates Ca(2+) transport in inside-out plasma-membrane vesicles
      from erythro cytes. Conversely, sphingosine, which is reported to act in many
      systems antagonistically with ceramide, showed an inhibitory effect on Ca(2+)
      ATPase activity. This inhibition was also observed on the calmodulin-stimulated
      enzyme. These results, taken together, suggest that ceramide and sphingosine act
      antagonistically on the plasma-membrane Ca(2+)-ATPase. This is in accordance with
      the frequently reported opposite effect of these sphingolipids on intracellular
      Ca(2+) concentration.

PMID- 11829763
TI  - Metal imbalance and compromised antioxidant function are early changes in prion
      disease.
AB  - The prion protein (PrP) has been shown to bind copper. In the present study we
      have investigated whether prion disease in a mouse scrapie model resulted in
      modification of metal concentrations. We found changes in the levels of copper
      and manganese in the brains of scrapie-infected mice prior to the onset of
      clinical symptoms. Interestingly, we noted a major increase in blood manganese in
      the early stages of disease. Analysis of purified PrP from the brains of scrapie
      infected mice also showed a reduction in copper binding to the protein and a
      proportional decrease in antioxidant activity between 30 and 60 days post
      inoculation. We postulate that alterations in trace-element metabolism as a
      result of changes in metal binding to PrP are central to the pathological
      modifications in prion disease.

PMID- 11829764
TI  - Effect of C-domain N-glycosylation and deletion on rat pancreatic alpha-amylase
      secretion and activity.
AB  - Even though all animal alpha-amylases include glycosylation sequons (Asn-Xaa
      Thr/Ser) in their sequences, amylases purified from natural sources are not
      quantitatively glycosylated. When wild-type rat pancreatic alpha-amylase, which
      contains two glycosylation sequons, was expressed in animal cell lines the
      protein displayed a very low rate of glycosylation (approx. 2%), even after
      Brefeldin A treatment to increase the contact with the glycosylation machinery.
      Site-directed mutagenesis of the first glycosylation sequon (Asn(410)-->Gln)
      resulted in 90% of the protein being glycosylated at the second glycosylation
      sequon (Asn(459)). Mutation of the second sequon completely inhibited
      glycosylation. In order to ascertain if the interference in the glycosylation of
      Asn(459) that was eliminated by the Asn(410)-->Gln mutation could be due to the
      position of the asparagine residue in the Cys(448)-Cys(460) disulphide bridge,
      these cysteine residues were mutated to serine residues. The resulting mutant was
      found to be 100% glycosylated. All mutants with mutations in the C-domain had
      specific activities identical to that of the wild-type enzyme, indicating that
      enzymic activity is independent of the structure and modification of the C
      terminal domain. To further test the independence of the C-domain with respect to
      the two N-terminal domains of the protein, which harbour the catalytic site, the
      last seven of the ten beta?beta-strands that make up the beta-sandwich
      configuration of the domain were deleted. The truncated protein was not secreted
      from cells and all enzyme activity was destroyed. These observations show that
      Asn(459) is the only site that can be glycosylated in wild-type amylase, and
      confirm the relative independence of the C-terminal domain of alpha-amylase with
      respect to enzyme activity. In addition, they also establish that the C-terminal
      domain is absolutely essential for the correct post-translational folding of the
      enzyme that is responsible for its activity and allows for its secretion.

PMID- 11829765
TI  - [Cellular immune function influence on postoperative patients with hepatocellular
      carcinoma and the clinical effect of TILs treatment].
AB  - OBJECTIVE: To investigate the cellular immune function influence on postoperative
      patients with hepatocellular carcinoma (HCC) and clinical effect of TILs, rIL-2
      and cyclophosphamide treatment. METHODS: Eight postoperative HCC patients were
      treated with TILs, rIL-2 and cyclophosphamide. Six patients were infused from the
      hepatic artery, and the other 2 infused from the portal vein. RESULTS: The IL-2
      NK activity, Tsubsets, CD4(+)/CD8(+) level in the peripheral blood of all
      patients increased and the IL-6, TNF level of most patients decreased (P > 0.05,
      P < 0.01). For 6 - 18 month follow-up after management, 6 patients with radical
      tumor resection showed no recurrence. One patient having palliative resection
      showed no remnant tumor enlargement. One patient with increased TNF level for 8
      IU died from hepatic failure 8 months after chemotherapy. CONCLUSIONS: The TILs,
      rIL-2 and cyclophosphamide treatment of postoperative HCC patients is effective
      in improving antitumorgenic immune function, preventing tumor recurrence, and
      restraining remnant tumor growth.

PMID- 11829766
TI  - [Hepatic resection with removal of tumor thrombi for hepatocellular carcinoma
      with tumor thrombi in portal vein and curative analysis].
AB  - OBJECTIVE: To study the therapeutic effects of surgical treatment for
      hepatocellular carcinoma (HCC) with tumor thrombi in the main trunk or the first
      branch of the portal vein (PVTT) and factors affecting prognosis. METHODS: 111
      HCC patients with PVTT underwent hepatic resection with removal of tumor thrombi
      in the first left or the right branch of the portal vein or removal of tumor
      thrombi by direct opening of the main trunk of the portal vein. Hepatic artery
      infusion and/or portal vein infusion were performed after hepatic resection with
      removal of tumor thrombi for HCC with PVTT in 22 of the patients. Among 111
      patients, 32 received postoperative transhepatic arterial chemoembolization
      and/or portal vein chemotherapy. Conservative treatment and surgical exploration
      or hepatic artery ligation (HAL) and infusion (HAI) and/or portal vein infusion
      (PVI) were performed in other 14 and 20 HCC patients with PVTT, respectively.
      RESULTS: The 1-, 2-, 3-, 4- and 5- year survival rates were 61.7%, 36.2%, 32.3%,
      24.4% and 22.4% in the resected group, respectively, whereas 14 HCC patients with
      PVTT treated conservatively died in three months and the 1-, 2- year survival
      rates were 6.0% and 0 in the 20 patients with surgical exploration or HAL and HAI
      and/or PVI respectively. CONCLUSIONS: Hepatic resection with removal of tumor
      thrombi for HCC with PVTT should be encouraged for the prolongation of life span
      and quality of life.

PMID- 11829767
TI  - [Resection of caudate lobe of liver: report of 26 cases].
AB  - OBJECTIVE: To summarize the experience in caudate lobectomy for 26 cases.
      METHODS: Caudate lobectomy was performed in 26 cases by Peng's multifunctional
      operative dissector (PMOD) to transect the liver parenchyma (Curettage and
      Aspiration technique). Primary liver cancer was noted in 18 cases, hilar
      cholangiocarcinoma in 4, gallbladder carcinoma in 1, right adrenocortical
      adenocarcinoma in 1, hepatoangioma in 1 and hepatoangiosarcoma in 1. Five cases
      underwent isolated caudate lobectomy, 1 combined caudate lobectomy with right
      trisegmentectomy, 6 combined caudate lobectomy with right hemihepatectomy, 9
      combined caudate lobectomy with left hemihepatectomy, and 5 combined caudate
      lobectomy with segmentectomy. RESULTS: The operations were carried out
      successfully. Follow up for 2 - 23 months, 1 case died from pulmonary infraction
      2 weeks after operation, 1 died from lung metastasis 2 months after operation, 10
      died from tumor recurrence or metastasis 3, 11, 12, 15, 15, 15, 15, 19, 30, 30
      months after operation respectively. The other 14 cases are still alive for 2 to
      18 months. CONCLUSIONS: With PMOD, it is possible to dissect the structure
      precisely. Therefore the caudate lobe can be isolated from the three porta
      hepatis without much difficulty. Caudectomy can be performed safely.

PMID- 11829768
TI  - [Management of retrohepatic inferior vena cava injuries in hepatectomy for
      neoplasm].
AB  - OBJECTIVE: To evaluate the management of injured retrohepatic inferior vena cava
      during hepatectomy for neoplasm. METHODS: Step-by-step hepatic vascular
      exclusion, finger pressing, finger pinching, and surface-to-surface sewing up
      were used in the management of injured retrohepatic inferior vena cava in 16
      cases of hepatic resection. RESULTS: In all cases, bleeding was stopped
      immediately after the procedure without any death and rebleeding. All cases
      survived after 6 - 18 month follow-up. CONCLUSIONS: The methods mentioned above
      are simple, useful, time-saving, safe and effective.

PMID- 11829769
TI  - [Multivariate analysis of prognostic factors after hepatectomy for primary liver
      cancer].
AB  - OBJECTIVE: To determine the prognostic factors for primary liver cancer (PLC)
      after hepatectomy. METHODS: 182 patients who underwent hepatectomy for PLC from
      1988 to 1996 were included for univariate and Cox multivariate analysis. 20
      factors contributed to the long-term survival rate (SR) and the disease-free SR
      were analysed. RESULTS: The cumulative SR (n = 182) in 5 years was 43.3%. The 5
      year SR and disease-free SR in the curative resection (CR) group (n = 156) were
      48.0%, 24.9%, respectively. Multivariate analysis revealed that classification of
      CR and differentiation grade were significant factors for the long-term SR, and
      classification of CR and Child-Pugh's classification were significant factors for
      the disease-free SR. The 5-year SR and disease-free SR for pathological CR,
      clinical CR and non-CR (palliative resection) groups were 61.1%, 20.4%, 0 and
      28.8%, 15.5%, 0, respectively. CONCLUSIONS: The classification of CR is the
      determining prognostic factor. Pathological CR is the first option for patients
      with requirements. To control liver disease and improve adjuvant therapy are
      essential to decreasing the recurrence and metastasis rates.

PMID- 11829770
TI  - [The relationship between tumor necrosis factor and injuries of liver graft and
      lung after orthotopic liver transplantation in rats].
AB  - OBJECTIVE: To study the relationship between tumor necrosis factor alpha
      (TNFalpha) levels and ischemia-reperfusion injury of liver graft and lung after
      different cold-storage time during the early stage after orthotopic liver
      transplantation in rats. METHODS: Orthotopic liver transplantation was performed
      in SD rats. The survival rates, the pathology of liver graft and lung and the
      peripheral seral ALT levels were observed and the bile secretion volume and
      TNFalpha activities of post-hepatic blood were examined at regular intervals. The
      animals were divided into 3 groups: control, 4 h cold-storage group, and 6 h cold
      storage group (4 degrees C Ringer's solution). RESULTS: All the animals in the
      control and the 4 h group survived over 60 days, and none survived over 3 days in
      the 6 h group. The bile secretion volumes were larger in the control and the 4 h
      group than in the 6 h group (P < 0.05), and the ALT levels were lower in the
      control and 4 h group than in 6 h group (P < 0.05). The TNFalpha activity was not
      detected in the control but elevated significantly in the 6 h group, peaked, 2 h
      after the operation, and only slightly elevated in the 4 h group at the same time
      (P < 0.05). There were significant focal necrosis of liver graft and alveolar
      edema and leukocyte infiltration in the lungs in the 6 h group but no obvious
      injuries were observed in the 4 h group and the control. CONCLUSIONS: TNFalpha
      may contribute to the pathogenesis of ischemia-reperfusion injury of liver graft
      and pulmonary complications during the early stage after orthotopic liver
      transplantation. TNFalpha possibly originates from Kupffer cells of liver graft.

PMID- 11829771
TI  - [The characteristics and management of shotgun wounds of the extremities].
AB  - OBJECTIVE: To discuss the characteristics, classification and the problem of
      management for shotgun wounds of the extremities. METHODS: 82 shotgun wounds of
      the extremities, classified according to the modified rule form Sherman and
      Ordog's, were treated by "incision and drainage" initially, and were closed in
      primary, delay and later phase. The fractures were fixed by plaster, external
      fixator, simple internal fixator or plate fixation. Vascular injury was repaired
      by suture end-to-end or autograft. The injured nerves were treated in the primary
      or later period. RESULTS: The rate of infection was the highest in the primary
      closed wound, and the healing time was the longest in the later closed wound. The
      rate of infection was much higher in the fracture fixed by plate than the others.
      The results of nerve recovery in primary repair were not significantly different
      (except 2 case infection) from those in the later repair. CONCLUSIONS: A
      significant difference was noted between shotgun wound and other wound. Removal
      of wadding, prevention of fascial compartment syndrome, repeat planned
      exploration of wound, proper wound closing, external fixation of fracture,
      vascular debridement before anastomosis and delayed nerves repair contribute to a
      successful outcome in patients with extremity shotgun wounds.

PMID- 11829772
TI  - [Nontransitional cell tumor of the bladder].
AB  - OBJECTIVE: To study the experience in the treatment and diagnosis of the
      nontransitional cell tumor of the bladder, and to improve the overall survival
      rate. METHODS: The records were reviewed that 18 patients with nontransitional
      cell tumor of the bladder treated from Jan. 1990 to Dec. 1997 (5.1% of the 352
      bladder tumors in the same period). 16.7% of the patients had benign tumor, 83.3%
      malignant. Of the latter 73.3% were invasive. The overall rate of palliative
      treatment, partial or total cystectomy was compared retrospectively. RESULTS:
      Three patients with benign tumor are alive. The overall survival rate of 14
      patients with malignant tumor at 1, 3 and 5 years was 85.7%, 66.7%, and 57.1%.
      CONCLUSIONS: Most of the patients had haematuria and irritable bladder symptoms.
      The proper treatment was partial or total cystectomy. The prognosis was
      apparently related to the tumor stage and therapy method.

PMID- 11829773
TI  - [Severe emphysema treated by lung volume reduction surgery].
AB  - OBJECTIVE: To investigate criteria of screening surgical candidates and clinical
      effects of lung volume reduction surgery (LVRS) for severe emphysema. METHODS: 20
      patients with severe emphysema under went resection of the targeted overinflated,
      destructive and dysfunction pulmonary tissue by linear stapler or Endo-GIA and
      sternotomy approach or video-assistant thoracoscopy. 20% - 30% of the volume of
      each lung was resected. RESULTS: After operation, dyspnea evidently alleviated or
      disappeared. Pulmonary function: FEV(1) increased by 41.4%, RV, TLC decreased by
      27.5% and 22.7% respectively. PaO(2) increased by 12.6 mm Hg. Six-minute walk
      test increased by 55.8%. There was significant difference above indexes between
      preoperation and postoperation (P < 0.01). Eight patients were complicated by a
      prolonged air leakage (> 7 days), and one by irritable digestive ulcer and
      bleeding. No death occurred during perioperation. CONCLUSIONS: LVRS is an
      effective for severe emphysema.

PMID- 11829774
TI  - [Extensive transbasal approach for removal of tumours in the nasal, sphenoid and
      clival regions].
AB  - OBJECTIVE: To improve operative results of removal of the tumors in midline
      cranial base and the reconstruction of defect at frontal base through
      modification of the operative approach and techniques. METHODS: Extensive
      transbasal approach was used in 15 patients with tumours in the nasal, sphenoid
      and clival regions. RESULTS: The tumor was removed in 10 patients, near totally
      removed in 4 and partial removed in 1. The operative results of all patients were
      excellent except an elderly patient with mild operative morbidity. CONCLUSIONS:
      The procedure we used expand the operative indications for the tumors situated at
      the midline cranial base and improve the operative results. The procedure has
      advantages such as wide operative space, reliable reconstruction of the frontal
      base, and no severe complications.

PMID- 11829775
TI  - [External valvuloplasty for deep venous valve insufficiency of legs].
AB  - OBJECTIVE: To study and evaluate the therapeutic effects of external
      valvuloplasty for deep venous valve insufficiency of the legs. METHODS: External
      valvuloplasty of the femoral vein valve was performed in 26 patients (37 legs)
      with deep venous valve insufficiency of the legs. Among them, 12 were male and 14
      were female. These patients ranged in age from 16 to 69 years (x +/- s, 50.8 +/-
      10.0). External valvuloplasty of the first pair of the superficial femoral vein
      valve was carried out in all the legs. External valvuloplasty of the second pair
      of the superficial femoral vein valve was added in 7 legs and valvuloplasty of
      the common femoral vein valve in 6 legs. RESULTS: Venous claudication, swelling,
      aching disappeared in 81.1% patients (30/37), obviously improved in 18.9% (7/37)
      and varicose veins disappeared in all legs. Ulcer healing was seen in 7/9
      patients. Deep venous valve sufficiency was demonstrated in 89.2% patients
      (33/37), and reflux I degrees - II degrees in 4 legs by color Doppler.
      CONCLUSIONS: External valvuloplasty is effective in treating deep venous valve
      insufficiency of the legs.

PMID- 11829776
TI  - [The value of 99mTc-MIBI image axillary lymph node in selecting operative method
      for breast cancer].
AB  - OBJECTIVE: To retain axillary lymph node not infiltrated by cancer cell. METHODS:
      Breast cancer was diagnosed by fine needle aspiration cytology (FNA) or tumor
      biopsy before operation. Axillary lymph node was examined by surgery and (99m)Tc
      MIBI image. Pathological examination of the axillary tissue after operation is
      used as gold standard in comparison of the two examination methods. RESULTS: The
      sensitivity, specificity, and accuracy of surgical examination are lower than
      those of (99m)Tc-MIBI image (P < 0.05). CONCLUSIONS: (99m)Tc-MIBI image combined
      with surgical examination can be used as a method for retaining axillary lymph
      node.

PMID- 11829777
TI  - [Deep venous incompetence of legs: experimental studies].
AB  - OBJECTIVE: To seek best wrapping materials of valvular wrapping operation of deep
      veins in the lower limbs and to understand the value of diagnostic value of
      duplex scanning for incompetence of the deep veins and the function of the
      popliteal valve. METHODS: Strips of the autogenous saphenous vein, autogenous
      fascia lata and PEFE graft were used respectively as the material for valve
      constriction. The results were compared of duplex scanning and trans-popliteal
      venography. RESULTS: In the saphenous vein and fascia lata groups, diffuse
      fibrosis and marked narrowing of the femoral vein were found, whereas in the
      vascular graft group the graft was intact without prominent fibrosis and
      narrowing of the vein. The accurate rates of duplex scanning and trans-popliteal
      venography were 91.86%. at the same time the thigh and popliteal valve was closed
      when held breath. CONCLUSIONS: Vascular graft is the best constriction material.
      Duplex scanning is a important method. Popliteal valve is an important barrier
      for protecting the function of the deep vein.

PMID- 11829778
TI  - [The percentage of free prostate specific antigen used in detecting prostate
      cancer].
AB  - OBJECTIVE: To evaluate the value of the percentage of free prostate specific
      antigen in detecting prostate cancer. METHODS: Serum free prostate specific
      antigen (F-PSA) and total PSA were measured with immunoradiometric assay, and the
      free/total PSA ratio was calculated. In 117 patients, 31 had prostate carcinoma
      and 86 BPH. RESULTS: The free/total PSA ratio was lower in patients with prostate
      cancer than in those with BPH. If the total serum PSA level was limited with in 4
      - 10 ng/ml, the free/total PSA ratio can be used in the differential diagnosis of
      prostate cancer and BPH except total PSA. CONCLUSIONS: The free/total PSA ratio
      can be used in the differential diagnosis of prostate cancer and BPH, especially
      when serum PSA level is limited with in 4 - 10 ng/ml.

PMID- 11829779
TI  - [Plasma thyroid hormones during cardiopulmonary bypass].
AB  - OBJECTIVE: To study the changes and clinical significance of plasma thyroid
      hormones were during cardiopulmonary bypass (CPB). METHODS: Plasma thyroid
      hormones was studied in 36 patients during open heart surgery under CPB. Blood
      samples were taken preoperatively, and 1, 2, 3, 4, 5 days postoperatively.
      Doppler echocardiography was performed in 16 patients before and after surgery
      for evaluating heart function. RESULTS: Before CPB, the levels of thyroid
      hormones were within normal range. At early stage after CPB, the levels of FT(3),
      FT(4), TT(3) and TT(4) were significantly decreased and increased. Both TSH and
      rT(3) were increased significantly after CPB (P < 0.05) and reached their highest
      levels at the first postoperative day. TSH and rT(3) were gradually dropped
      subsequently, but TSH returned to the basic level and the level of rT(3) was
      still high. A positive relation was seen between plasma thyroid hormones and
      cardiac function. CONCLUSIONS: The changes of plasma thyroid hormones are closely
      related to cardiopulmonary bypass and could result in postoperative cardiac
      disfunction.

PMID- 11829780
TI  - [Biological mechanism of macrophage activation by wear particles at the bone
      implant interface].
AB  - OBJECTIVE: To observe the response of membrane Ca(2+) channel of macrophage-like
      cells (MCs) to wear particles and analyze the cytoplasmic [Ca(2+)]i change in
      macrophage activation at the bone-implant interface. METHODS: The synoviocyte
      system of normal hip joint was established in vitro. Immunohistochemical
      technique (SABC) with CD68 Mab was used to differentiate MCs and fibroblast-like
      cells (FCs) in the system, and the time when MCs begin to perform phagocytosis
      was determined by SEM. 1.5 mg/ml (W/V) Ti alloy, Co-Cr alloy or UHMWPE particles
      suspension was added into the system to monitor the [Ca(2+)]i change in the MCs
      by confocal laser scanning microscope (CLSM). RESULTS: Phagocytosis of MCs
      happened after 6 hours, but within 1 hour the Ca(2+) channel of their cell
      membrane opened for 1 - 6 times and caused rapid and transient pulses of
      [Ca(2+)]i in cytoplasm after different period of incubation. There was no
      significant difference between times or range of the [Ca(2+)]i pulse (P > 0.05).
      The group of UHMWPE particles had the longest incubation period (P < 0.05), but
      the interval of pulses was shorter than that in the group of Co-Cr alloy
      particles (P < 0.05). [Ca(2+)]i pulses still appeared when MCs were incubated by
      indomethecin (P > 0.05), but the phenomenon could be blocked by nimodipin.
      CONCLUSIONS: Activation of macrophages at the bone-implant-interface could happen
      before they phagocytose wear particles. The primary switch-on mechanism of
      osteolysis mediated by cytokines at the bone-implant interface may be the opening
      of membrane Ca(2+) channel and pulse-like Ca(2+) influx of macrophages when
      stimulated by wear particles.

PMID- 11829781
TI  - [Detection of apoptosis exposed to 10-hydroxycamptothecin in T24 human urinary
      bladder cancer cells].
AB  - OBJECTIVE: To study whether 10-hydroxycamptothecin (HPT) can induce apoptosis in
      bladder cancer cell and establish methods for detecting apoptotic cells. METHODS:
      Human urinary bladder cancer cell line (T24) was exposed in vitro to different
      concentrations of 10-hydroxycamptothein for various lengths of time. Flow
      cytometry, Hochest 33258 and Hematoxylin staining were used to determine the
      induction of apoptosis after use of HPT. DNA gel analysis was also carried out to
      detect DNA fragmentation. RESULTS: Cell shrinage, nuclear fragmentation and
      condensed chromosomes showed that apoptosis can be induced by HPT within the
      concentration of 0.01 - 10 microg/ml. The flow cytometry analysis showed that the
      percentage of apoptotic cells were related to the concentration and the time of
      induction. T24 cell line exposed to HPT experienced internucleosomal DNA
      fragmentation by producing a typical ladder pattern on agarose gel
      electrophoresis. The detection of minimum exposure time for HPT-induced apoptosis
      in T24 cells showed that 3 hours of exposure to HPT were enough to trigger
      internucleosomal DNA fragmentation. Compared to Hochest 33258 staining,
      Hematoxylin staining was more easy, rapid and accurate to detect apoptosis.
      CONCLUSIONS: The induction of apoptosis exposed to HPT in T24 human urinary
      bladder cancer cells is a good model for further studying urinary bladder cancer.
      Hematoxylin staining is a useful method for detecting apoptosis.

PMID- 11829782
TI  - [Can esophagogastric anastomosis prevent gastroesophageal reflux].
AB  - OBJECTIVE: To investigate the possible anti-reflux function of esophagogastric
      anastomosis in the patients after receiving resection of cardiac cancer. METHODS:
      One hundred and ninety-two patients were studied by video-assisted gastroscopy,
      manometry, 24-h pH esophageal monitoring, radioscintigraphy and scanning electron
      microscopy. RESULTS: Abnormalities were found in 90.2% of patients through
      endoscopy. Resting pressure in esophageal body was higher than that in normal
      controls, and in the stomach, lower. Twenty-four hour pH monitoring demonstrated
      that gastroesophageal reflux (GER) did not occur when the patients slept in semi
      reclining position, and occurred in all patients when slept in supine position.
      Scintigraphic study showed that 2/3 of the patients had reflux, occurrence of
      which was not affected by the length of postoperative period. Scanning electron
      microscopic examination showed that degeneration, exfoliation of esophageal
      mucosal epithelial cell, and derangement of micro-fold and inflammatory oedema of
      cytomembrane may be directly caused by reflux. CONCLUSIONS: GER exists in the
      majority of the patients after esophagogastrectomy and esophagogastrostomy for
      cardiac cancer. The occurrence of GER is not affected by the length of
      postoperative period. Some detecting methods fail to show the existence of GER,
      and 24-h pH monitoring is the most reliable method for detecting GER. Sleep in
      semireclining position is an effective method of preventing GER in postoperative
      patients.

PMID- 11829784
TI  - [Function research of esophageal lower sphincter in infant with hiatal hernia].
AB  - OBJECTIVE: To investigate the relationship between gastroesophageal dynamics of
      infantile hiatal hernia (HH) and gastroesophageal reflux (GER) and to assess the
      curative effects of antireflux surgery. METHODS: Ambulatory 24-hr esophageal pH
      metry and esophageal manometry were studied in 26 patients with HH before and
      after surgery. RESULTS: By radiology, patients were divided into group of sliding
      HH (n = 16, group I) and group of para-esophageal or combined HH (n = 10, group
      II). All patients showed GER. The duration of the longest episode, and the
      percentage of the time at pH < 4 were significantly greater in lying position
      than those in upright position (P < 0.05). All parameters were significantly
      decreased after operation (P < 0.01). Lower esophageal sphincter length (LESL)
      increased significantly postoperatively. In group I, lower esophageal sphincter
      pressure (LESP) and barrier pressure (BP) was increased after surgery, but no
      significant difference was seen in LESP and BP in group II. Intragastric pressure
      (GP) significantly reduced after operation. GP in group II before operation was
      higher than that in group I (P < 0.05). A second high pressure zone in the
      esophagus was found in 67% of patients in group I and 14% patients in group II.
      CONCLUSIONS: Most patients with infantile HH and GER decreased LESL, LESP and
      increased GP. Differential gastroesophageal dynamics is associated with types of
      hiatal hernia. It is very important to remain enough LESL in mechanism of Dor
      antireflux surgery. To prevent respiratory infection is an important measure to
      prevent patients from relapse after surgery.

PMID- 11829783
TI  - [Clinical application of esophageal manometry and 24-hour esophageal pH
      monitoring].
AB  - OBJECTIVE: To evaluate the clinical application of esophageal manometry and 24
      hour esophageal pH monitoring. METHODS: From 1990 to 1996, ambulatory esophageal
      manometry and 24-hour esophageal pH monitoring were performed on 101 patients
      with different functional esophageal diseases, including Barrett's esophagus 54
      patients non-cardiac chest pain (10) and post-cholecystectomy (37). Esophageal
      motility studies were made to compare the effects of different anti-reflux
      therapies, to identify primary esophageal motility disorders, to assess the
      effect of anti-acid drugs, and to study the relationship between esophageal
      motility disorder and other non-esophageal origin disease. RESULTS: In this
      study, anti-reflux surgery was better than medical therapy in controlling
      gastroesophageal reflux (GER) for Barrett's esophagus. Esophageal manometry was
      the best method for detecting primary esophageal motility disease. Omeprazole was
      superior to cimetidine in terms of control of GER and reduction of gastric
      acidity. Cholecystectomy resulted in GER and many symptoms after surgery appeared
      to have an esophageal origin. CONCLUSIONS: Esophageal manometry and 24-hour
      esophageal pH monitoring are the most sensitive and specialized methods for
      detecting esophageal motility disorders. They are superior to other routine
      diagnostic methods such as radiology and endoscopy.

PMID- 11829785
TI  - [Evaluation of pre- and post-operational esophageal manometric findings with
      achalasia].
AB  - OBJECTIVE: To evaluate the manometric feature of pre- and post-operation with
      achalasia and the result of surgical myotomy through abdominal incision. METHODS:
      The manometric studies were performed in 23 pre- and 11 post-operational
      patients, including 11 patients who received both pre- and post-operational
      studies. 24 hour pH monitoring was performed in 11 after surgical myotomy.
      RESULTS: Achalasia, a motor disorder of the esophageal body, and hypertension of
      the resting LES impaired relaxation. The incidence of reflux was 22.2%.
      CONCLUSIONS: Surgical myotomy through abdominal incision is an effective
      procedure. It is necessary to avoid LES incompetence or reflux esophagitis.

PMID- 11829786
TI  - [Functional improvement of remnant stomach after proximal subtotal gastrectomy
      for cardiac cancer].
AB  - OBJECTIVE: To evaluate the function of the remnant stomach after proximal
      subtotal gastrectomy for cardiac cancer and to improve the life quality of post
      surgical patients. METHODS: 17 patients with cardiac cancer underwent proximal
      subtotal gastrectomy combined with disconnection of pyloric sphincter (PSG + DPS)
      by finger pressing. Intraoperative pyloric manometric studies were performed in
      the 17 patients before and after DPS. Five subjects who underwent laparotomy for
      non-esophagogastric reasons was taken as controls. Total bile acids (TBA) in
      gastric juice was tested in the 17 patients at 5th postoperative day, and
      radionuclide gastric emptying was also studied from the 18th to 20st
      postoperative day. RESULTS: Both pyloric resting pressure and pyloric contracting
      pressure were significantly decreased after DPS (P > 0.01). In comparison with
      normal subjects, PCP was increased before DPS (P > 0.01) and decreased after the
      procedure (P < 0.05). However, PRP did not show significant differences before (P
      > 0.05) and after (P > 0.05) DPS. There were no significant differences regarding
      TBA content in gastric juice in PSG + DPS group, PSG group, and normal subjects
      (P > 0.05). The time required for the stomach to empty half of its radioactive
      contents (T1/2) was longer in the patients having PSG only than those undergoing
      PSG + DPS (P < 0.01) and normal controls (P < 0.05). However, there were no
      significant differences regarding T1/2 between the patients with PSG + DPS and
      normal controls (P > 0.05). CONCLUSIONS: The emptying of remnant stomach after
      subtotal gastrectomy for cardiac cancer is delayed because of the increase of
      emptying-resistance and decrease of peristalsis. PSG combined with DPS not only
      improves gastric emptying, but also prevents duodenogastric reflux. Consequently,
      postoperative life quality of the patients with cardiac cancer can be effectively
      improved.

PMID- 11829787
TI  - [Evaluation of therapeutic effects of portoenterostomy: reported of 426 cases].
AB  - OBJECTIVES: To investigate the selection of the types of anastomosis and to
      evaluate the therapeutic effects of portoenterostomy. METHODS: From 1993 to 1998,
      426 patients with obstructive jaundice underwent portoenterostomy. The patients
      included 236 cases (56%) of hilar strictures in hepatolithiasis, 98 cases (23%)
      of end-stage periampullary tumors, 64 cases (15%) of proximal cholangiocarcinoma,
      and 28 cases (6%) of congenital choledochus cyst. Reconstruction of biliary tract
      was performed after resection of affected duct or palliative bypass for end-stage
      carcinoma. The types of anastomosis included extra or hilar hepatic
      bilioenterostomy (160 cases, 37%), and intra-hepatic duct anastomosis with
      different type of hepatectomy (266 cases, 63%), in which anastomosis was
      performed by round ligament approach (34 cases, 8%), and anastomosis through
      gallbladder fossa (15 cases, 4%). RESULTS: Short- and 1-6 year follow-up showed
      that jaundice of patients was completely relieved by suitable type of
      bilioenterostomy. CONCLUSIONS: The good therapeutic effects of bilioenterostomy
      are based on the correct selection of anastomosis methods.

PMID- 11829788
TI  - [Cervical lymph node metastasis and blood metastasis of thyroid cancer].
AB  - OBJECTIVE: To evaluate the relevant factors for lymph cervical node metastases
      and blood metastases of thyroid cancer and to raise the level of diagnosis and
      treatment. METHODS: 225 cases of thyroid cancer were treated from Jan. 1984 to
      Dec. 1992. Their clinical characteristics, treatment, and pathologic features
      were described. RESULTS: The metastasis of thyroid cancer was related to its
      pathologic and invasive features. Papillary and squamous cell carcinomas were
      characterized by local lymph metastasis. Their metastasis rate was 44.7%, and 3/3
      respectively. Follicular carcinoma showed good differentiation but vessel
      metastasis with a metastatic rate of 18.2%. The metastasis rate was high and the
      prognosis poor, in undifferentiated cancer. CONCLUSIONS: Better treatment results
      may be achieved if proper management of thyroid cancer is based on its pathologic
      type and extent of local infiltration.

PMID- 11829789
TI  - [Slow transit constipation treated by surgery: analysis of 17 cases].
AB  - OBJECTIVE: To explore the operative indications, prognosis, and possible
      pathogenic factors of slow transit constipation (STC). METHODS: 17 cases with STC
      who had undergone colectomy were analysed. RESULTS: Bowel movement frequency was
      once per 4 to 14 days in all of the patients, who had had long-term laxative
      abuse. Delayed colonic transit was demonstrated in all patients, 82.4% of them
      were accompanied by outlet obstructive constipation (OOC) and 50% showed abnormal
      sex hormones. Reduced numbers of argyrophilic neurons and vacuolar degeneration
      of axons were demonstrated at the myenteric plexus pathologically. Three patients
      had adhesive ileus postoperatively and one patient suffered from difficult
      evacuation again 5 years after the operation. CONCLUSIONS: Colectomy is highly
      effective in alleviating symptoms in patients with STC, and pelvic floor disorder
      of OOC should be treated simultaneously.

PMID- 11829791
TI  - [Reinfusion of autologous shed blood after joint replacement].
AB  - OBJECTIVE: To evaluate the results of reinfusion of autologous shed blood after
      joint replacement. METHODS: From February 1996 to March 1998, we selected 36
      patients for 56 joint replacements. Apart from preoperative donation of
      autologous blood, all patients received transfusion of unwashed autologous
      drained blood from hips and knees after arthroplasty. The CBCIIConstaVac blood
      conservation system was used to salvage shed blood. Among the patients, 8 hips
      and 48 knees were involved. 12 patients had rheumatoid arthritis, 16
      osteoarthritis, 5 ankylosing spondylitis, and 3 other arthritis. RESULTS: 36
      patients received 24 260 ml (50%) autologous shed blood, 9 700 ml (20%) reserved
      autologous blood, and 14 600 ml (30%) allogenic blood. 15 patients experienced
      transient febrile reaction at the time of reinfusion, no other clinic
      abnormalities were discovered after reinfusion. CONCLUSIONS: Reinfusion of
      autologous shed blood is a safe and effective to decrease the use of allogenic
      blood and avoid the complications of its transfusion.

PMID- 11829790
TI  - [Reconstruction of posterior cruciate ligament using bone-patellar tendon-bone
      autograft].
AB  - OBJECTIVE: To introduce the surgical procedures of posterior cruciate ligament
      (PCL) reconstruction using bone-patellar tendon-bone autograft and to evaluate
      the clinical effect of treatment of posterior instability. METHODS: Twenty cases
      of chronic instability of knee secondary to rupture of PCL underwent
      reconstruction of PCL using free autograft of bone-patellar tendon-bone by
      isometric tibial and femoral attachment through anterior approach of knee. Larson
      knee function score, patient subjective evaluation and physical testing were used
      to evaluate the effect of this procedure. RESULTS: In this series, the average
      point of Larson score was 62 preoperatively. By the period of 6 - 58 month follow
      up, the average point was 92. Subjectively 18 cases showed satisfactory results.
      Lachmann test showed negative results in all cases. The range of motion was 115
      degrees on the average. CONCLUSIONS: This method can provide a strong and stable
      PCL replacement. But the surgical procedure is more difficult than ACL
      reconstruction. Some factors for a successful operation include evaluation of
      instability, preparation of graft material, internal fixation of graft, isometric
      attachment, reconstruction of other structures of knee, and bearing tension of
      graft.

PMID- 11829792
TI  - [Surgical treatment of trigeminal neurinomas].
AB  - OBJECTIVE: To investigate the best surgical approach to remove of trigeminal
      neurinomas (TNs). METHODS: 75 patients with TNs in Huashan Hospital were reviewed
      retrospectively. RESULTS: In early group (1978 - 1984) conventional intradural
      approaches were used, and in late group (1985 - 1995) an epidural approach via
      the skull-base craniotomy was utilized. Total removal of was achieved in 58%
      (20/35) in the early group and 80% (32/40) (P < 0.05) in the late group.
      Temporary or permanent cranial nerves morbidities were 62.7%, 37% in the early
      group and 28.1%, 10% (P < 0.01) in the late group, respectively. CONCLUSIONS: The
      best surgical approach with microsurgical technique for removal of TNs is
      epidural approach or epiduro-transduro-transtentorial approach via a skull-base
      craniotomy except the tumor only confined to the posterior fossa.

PMID- 11829793
TI  - [Spontaneous renal rupture].
AB  - OBJECTIVE: To study clinical regularity of spontaneous renal rupture. METHODS: 16
      cases of this disease were reviewed. Renal carcinoma was found in 4,
      angiomyolipoma in 2, undetermined etiology in 3, and invasive colic cancer,
      kidney cyst, nephrolithiasis, SLE with nephritis, polycythemia vera, renal
      tuberculosis, portal hypertension in 1 each. RESULTS: CT demonstrated a
      sensitivity of 87.5% in identifying the underlying kidney mass, which was higher
      than that (25%) of B-type ultrasound and (0) KUB + IVU. Radical nephrectomy was
      carried out in 6 cases, renal-reserved operation in 5, and conservative treatment
      in 5. CONCLUSIONS: 60% of spontaneous renal rupture are due to kidney neoplasia.
      CT scanning is the most valuable diagnostic procedure. If the primary cause has
      not been clarified, close follow-up with periodic CT scanning might be mandatory.

PMID- 11829795
TI  - [Study of the relation between mutant gene in bile and hepatic metastasis of
      large intestinal carcinoma].
AB  - OBJECTIVE: To study the value of point mutant genes in the diagnosis of hepatic
      metastasis of large intestinal carcinoma. METHODS: Techniques of PCR-SSCP and DNA
      sequencing were used to detect point mutations of p53 and k-ras genes in primary
      focus, hepatic metastatic focus, and bile. RESULTS: 50 cases of large intestinal
      cancer were detected. 38 cases (76.0%) had p53 and k-ras gene mutations. p53 gene
      mutations were detected in 28 cases (56.0%) and k-ras gene mutations in 16 cases
      (32.0%). The same point mutant genes in bile with primary focus were detected in
      10 out of 12 patients with hepatic metastasis (83.3%). CONCLUSIONS: The tumor
      cells of hepatic metastasis show the same clonal origin with primary focal cells
      that had same point mutant genes. Detection of the point mutant genes in bile is
      of value in the diagnosis of hepatic metastasis of large intestinal carcinoma.

PMID- 11829794
TI  - [Malignant pheochromocytoma: diagnosis and treatment].
AB  - OBJECTIVE: To review the experience with the diagnosis and treatment of malignant
      pheochromocytoma. METHODS: Between 1986 and 1996, 7 patients with malignant
      pheochromocytoma were analysed. RESULTS: Compared with benign pheochromocytoma of
      adrenal gland, the malignant one usually exceeded 7.0 cm in diameter, irregular
      in shape, invading the surrounding tissue and the normal structure of the
      effected adrenal gland disappeared. Bleeding and necrotic area were seen in tumor
      mass, even seemed as a cystic lesion with thick wall. In some patients, blood
      catecholamine and urine VMA significantly elevated without hypertension. The
      separating phenomenon and progressive weight loss, accelerated ESR were
      characteristics of malignant pheochromocytoma. CONCLUSIONS: In some patients with
      malignant pheochromocytoma, histological findings are not consistent with their
      biological behaviors. Follow-up studies is mandatory in malignant
      pheochromocytoma as well as in benign one. Recurrence and/or metastasis after
      operation often occur in patients with malignant pheochromocytoma. In addition to
      early diagnosis and surgery, radiotherapy of tumor bed and systematic
      chemotherapy should be emphasized.

PMID- 11829796
TI  - [The level of expression of adhesion molecules CD44v6 and E-cadherin in
      colorectal cancer and analysis of correlates with metastasis].
AB  - OBJECTIVE: To determine the expression of adhesion molecules CD44v6 and E
      cadherin in colorectal cancer and its relation with metastasis. METHODS: The
      expression of CD44v6 and E-cadherin in 32 patients with colorectal carcinoma was
      investigated using immunohistochemical staining, which was performed on surgical
      specimens. RESULTS: No significant correlation with CD44v6 and histologic type,
      TNM and Dukes staging was noted, but it was significantly correlated with lymph
      node and hematogenous metastasis. E-cadherin was strongly expressed in normal
      epithelium examined. However, E-cadherin expression in colorectal carcinoma was
      reduced (positive rate 46.9%). Metastatic colorectal carcinoma showed significant
      reduction (positive rate 20%). CONCLUSION: CD44v6, E-cadherin immunoreactivity
      are significantly correlated with lymph node and hematogenous metastasis.

PMID- 11829798
TI  - [RBC and T lymphocyte subsets in patients with bladder carcinoma: immunological
      study].
AB  - OBJECTIVE: To study immune function of erythrocytes and the correlation with the
      change of T lymphocyte subsets in the patients with bladder cancer. METHODS: The
      red blood cell C(3)b receptor rate (C(3)bRR), immune complex rate (ICR) and four
      kinds of tumor erythrocyte rosette tests were determined in 34 cases of bladder
      transitional epithelial carcinoma. The subsets of T lymphocyte were also
      determined by using flow cytometry (FCM). 30 non-carcinoma patients that well
      matched in age and 20 healthy men were determined for comparison. RESULTS: The
      C(3)bRR, four kinds of tumor erythrocyte rosette rate, CD3, CD4 and CD4/CD8 ratio
      were lower in the bladder transitional epithelial carcinoma group than those of
      the control group. Meanwhile, ICR and CD8 were significantly elevated (P < 0.01).
      There was differentiation between G1 patients and G2 patients (P < 0.05). A
      positive correlation between C3bRR and the radio of CD4/CD8 was noted in the
      bladder transitional cell carcinoma group. CONCLUSIONS: Patients with bladder
      transitional cell carcinoma show lower erythrocyte function and disorder of T
      lymphocyte subsets. There is a close relationship between red cell immune
      function and T lymphocyte subsets. The cellular immune function (including the
      red cell immune function) in patients with poorly differentiated cells is lower.

PMID- 11829797
TI  - [Measurement of liver volume and its clinical significance in cirrhotic
      patients].
AB  - OBJECTIVE: To evaluate whether, preoperative measurement of liver volume is of
      value to the evaluation of tolerance to operation and long-term prognosis in
      cirrhotic patients with portal hypertension. METHODS: We assessed liver volume in
      18 cirrhotics and 31 noncirrhotic controls with 3-dimensional shaded surface
      display by CT twin. RESULTS: The liver volume in controls was positively
      correlated to the height (r = 0.42, P < 0.05). The average of liver volume in
      controls was (1 070.68 +/- 227.52) cm(3) and was different from that of
      cirrhotics (797.02 +/- 135.11) cm(3) (P < 0.05). Liver volume of cirrhotic
      patients with portal hypertension was related to their Child classification. The
      liver volume of patients in Child C group was significantly smaller than that of
      patients of Child B group. CONCLUSIONS: The patients with smaller liver volume
      are likely complicated by encephalopathy after shunting procedure. However, the
      liver volume is not significantly correlated with portal blood flux and
      portosystemic shunt index.

PMID- 11829799
TI  - [Relationship between PDGF-A, bFGF and proliferation of smooth muscle cells in
      vein grafts].
AB  - OBJECTIVE: To detect the relationship between platelet-derived growth factor-A
      (PDGF-A), basic fibroblast growth factor (bFGF), and proliferation of smooth
      muscle cells in vein grafts. METHODS: An animal model of autogenous vein graft
      was established by transplanting internal branch of the jugular vein to the
      common iliac artery by end-to-end anastomosis. 25 rats were used. The grafted
      veins were harvested at 6 h, 2 d, 1 w, 2 w and 4 w respectively after the
      operation. The expression of PDGF-A and bFGF in different stages after grafting
      procedure was observed immunohistochemically. RESULTS: The expression of PDGF-A
      peaked at 1 w, paralleled with proliferation of SMC, and was significantly higher
      than that at 6 h (P < 0.01). The expression of PDGF-A diminished gradually. At 4
      w, it was significantly lower than that at 1 w (P < 0.01). bFGF demonstrated
      bimodal pattern of the expression: the first peak of expression occurred by 2 d
      and the second peak by 2 w. The difference was significantly compared with other
      stages. CONCLUSIONS: The expression of PDGF-A 1 contributed to migration and
      proliferation of SMC. Except for contributing to proliferation of SMC, bFGF
      perhaps took part in endothelization.

PMID- 11829800
TI  - [Protective effects of bactericidal/permeability-increasing protein on the vital
      organ function after endotoxic shock in rats].
AB  - OBJECTIVE: To investigate the protective effects of BPI on the vital organ
      function after endotoxic shock in rats, and to provide experimental evidence for
      further clinical studies. METHODS: 12.5 mg/kg of E. coli 026:B6 LPS were bolus
      injected via i.a. to reproduce endotoxic shock. Immediately after injection of
      LPS, 5 mg/kg of BPI or equal volume of physiological saline were bolus injected
      via i.a. RESULTS: The survival time of shocked animals was prolonged in the BPI
      group, 24 h survival rate was higher than that in the saline group. The values of
      mean arterial pressure, left intraventricular systolic pressure, isovolemic
      ventricular pressure, and dp/dtmax in the BPI group were markedly higher than
      those in the saline group. The plasma glutamic-pyruvic transaminase and urea
      nitrogen levels were obviously lower than those in the saline group. The plasma
      endotoxin and TNF levels in the BPI group were significantly lower than those in
      the saline group. CONCLUSIONS: BPI has good protective effects on cardiac,
      hepatic, and renal function in endotoxic shock in rats, indicating that BPI might
      be useful in clinic treatment of sepsis/septic shock.

PMID- 11829801
TI  - [Experimental observation of origins of osteoblasts in guided bone regeneration
      in long bone].
AB  - OBJECTIVE: To study the origins of osteoblasts in guided bone regeneration (GBR)
      so as to understand the mechanism of GBR. METHODS: New Zealand rabbits were used.
      Standard ununited defect models were made in bilateral middle radial shaft of
      each rabbit. Randomly, one defect enveloped with silicon membrane as test,
      another without membrane as control. 12 rabbits were selected for X-ray
      examination weekly after procedure. 30 rabbits were divided into 6 groups, and
      sacrificed at 3 days, 1, 2, 3, 4, 5 weeks after surgery for histological
      observation by immunohistochemical staining of BMP, BGP. RESULTS: The sealed
      spaces were made by silicon membranes in the defects to prevent peripheral tissue
      ingrowing early. The defect spaces were filled by granulation tissue formed from
      proliferative endoperiosteal and medullary stromal cells in bone end.
      Histological characteristics after callus forming showed that there were 2 - 3
      layers of osteoblasts in the surface of callus, and granulation tissue in the
      center of bone defect. The transforming region existed between the extending
      callus and granulation tissue, which consisted of a few of cells and a lot of
      stroma. Early proliferative endo-periosteal and medullary stromal cells in the
      bone end were positive against BMP, BGP. Some cells in the transforming region
      were positive against BMP, BGP after callus forming. CONCLUSIONS: Osteoblasts
      derive from endoperiosteum and medullary stroma in the early stage of GBR and
      from granulation tissue formed by proliferative endo-periosteal and medullary
      stromal cells in the later stage.

PMID- 11829802
TI  - [The feature of pancreatic microcirculatory impairment in caerulein induced acute
      pancreatitis].
AB  - OBJECTIVE: To study the feature of pancreatic microcirculatory impairment in
      caerulein-induced acute pancreatitis. METHODS: The AP model of subcutaneous
      injection of caerulein was studied by intravital fluorescence microscopy of
      erythrocytes labeled by FITC (FITC-RBC) and by scanning electron microscopy of
      vascular corrosion casts and light microscopy of Chinese ink-injected/cleared
      tissues. RESULTS: Animals treated with caerulein showed hyper-amylases.
      Contractions of intralobular arteriolar sphincter, presence of vacuoles in all
      the layers of sphincter, gross irregularity in capillary network of acini were
      observed in caerulein-induced groups. The decrease of pancreatic capillary blood
      flow (P < 0.01), reduction of functional capillary density, and irregular
      intermittent perfusion (P < 0.05) were found. CONCLUSIONS: Impairment and
      contraction of pancreatic intralobular arteriolar sphincter are the initial
      microcirculatory lesions in the early phase of acute pancreatitis induced by
      Caerulein, and play a key role in the pancreatic ischemia and pancreatic
      microvascular failure in acute pancreatitis.

PMID- 11829803
TI  - [Effects of short veno-venous hemofiltration on severe acute pancreatitis].
AB  - OBJECTIVE: To estimate the effects of therapy of short veno-venous hemofiltration
      (SVVH, 4hr) on severe acute pancreatitis (SAP). METHODS: Twenty patients were
      divided randomly into hemofiltration group (HF, 10 pts) and non-hemofiltration
      group (NHF, 10 pts). The local, systemic manifestations were compared between two
      groups; and the concentration of serum pro-inflammatory cytokines (TNFalpha, IL
      1beta, IL-6, IL-8, sIL-2R) and anti-inflammatory cytokines (IL-2, IL-10) were
      determined at different observation points. RESULTS: In the HF and NHF group, the
      duration for disappearance of abdominal pain and tenderness, and amelioration for
      abdominal distension was (8.5 +/- 6.3) d vs. (90.0 +/- 49.0) d and (16.9 +/- 5.2)
      d vs. (63.4 +/- 36.0) d. CT scores at the 14th day and APACHE II scores at the
      10th day was (5.6 +/- 1.3) vs. (7.7 +/- 0.8) and (4.5 +/- 1.5) vs. (7.4 +/- 2.1).
      The average hospital stay and cost of therapy were (33.0 +/- 20.7) d vs. (56.4 +/
      16.0) d and (53,200 +/- 16,000) vs. (89,100 +/- 25,000) RMB (P < 0.05). The
      concentration of 5 serum pro-inflammatory cytokines at each observation points
      after hemofiltration was decreased significantly (P < 0.05) in the HF group. But
      the concentration of the two serum anti-inflammatory cytokines was increased
      significantly (P < 0.05) as compared with that of the NHF group. CONCLUSIONS:
      Through SVVH, the imbalance of pro-inflammatory and anti-inflammatory cytokines
      has been corrected at early stage; thus, the severity of the disease is
      ameliorated significantly and the efficacy of therapy is increased.

PMID- 11829804
TI  - [The effect of blood-pancreatic juice barrier on 5-fluorouracil in post
      pancreatoduodenectomy patients].
AB  - OBJECTIVE: To observe the distribution and the relationship of 5-Fu in the plasma
      and the pancreatic juice in post-pancreatoduodenectomy patients after 5-Fu given
      intravenously. METHODS: After 5-Fu (1.0 g/m(2)) was given intravenously in post
      pancreatoduodenectomy patients, blood and pancreatic juice were collected. The 5
      Fu concentrations were determined by HPLC and at last the penetration ratio (PR)
      of 5-Fu was studied with PCNONLIN. RESULTS: 5-Fu in the plasma penetrated the
      pancreatic tissue and crossed the blood-pancreatic juice barrier (BPJB) in post
      pancreatoduodenectomy patients (PR = 1.01 +/- 0.49). The concentration of 5-Fu in
      pancreatic juice was much higher than that in plasma. CONCLUSIONS: 5-Fu is
      suitable for adjuvant chemotherapy of pancreatic adenocarcinoma after
      pancreatoduodenectomy.

PMID- 11829805
TI  - [Effect of preoperative chemotherapy on apoptosis and tissues of pancreatic
      adenocarcinoma].
AB  - OBJECTIVE: To investigate the apoptosis and tissues change of pancreatic
      adenocarcinoma with or without preoperative chemotherapy and discuss the effect
      of preoperative regional chemotherapy on pancreatic adenocarcinoma cell. METHODS:
      Using the method of TUNEL and microscope, we determined the apoptosis of tumor
      cells and tissues changes in 30 pancreatic adenocarcinoma patients with or
      without preoperative chemotherapy. RESULTS: The ratio of apoptosis was much
      higher in the preoperatively treated group than in the untreated group (44.87 +/-
      27.78) and (3.6 +/- 3.76)/HP, (P < 0.01). The ratio of apoptosis was related to
      the tissue type of pancreatic adenocarcinoma. The ratio of apoptosis in the
      highly differentiated adenocarcinoma group was much higher than that in the
      middle or low differentiated adenocarcinoma group (P < 0.05, P < 0.01). The
      inflammatory reaction and the proliferous intima of vessels were more obvious in
      the preoperatively treated group than in the untreated group (P < 0.05, P <
      0.01). CONCLUSIONS: Preoperative regional chemotherapy can effectively inhibit
      pancreatic adenocarcinoma by inducing the apoptosis of tumor cells.

PMID- 11829806
TI  - [Diagnosis and treatment of gastric carcinoid tumors].
AB  - OBJECTIVE: To investigate the method for surgical diagnosis and treatment of
      gastric carcinoid tumors. METHODS: Clinicopathologic features of 9 patients with
      gastric carcinoid tumors were analyzed retrospectively. The patients were
      confirmed by biopsy at endoscopy or surgery. RESULTS: Eight of the 9 patients
      underwent elective operation, 6 showed gastric carcinoid tumors before operation
      found by biopsy at endoscopy. Five tumors were malignant and 4 benign. Two
      patients showed malignant carcinoid syndrome, but 5-HT and 5-HIAA were normal.
      CONCLUSIONS: Benign or malignant gastric carcinoid tumor depends upon tumor size,
      local lymph node invasion and distant metastases. The prognostic factor is based
      on benign or malignant tumors. Operation may be the first choice for such
      patients.

PMID- 11829807
TI  - [Biologic behavior and prognosis of patients with gastric cancer in young
      persons].
AB  - OBJECTIVE: To explore the relationship between the biological behavior and
      prognostic factors in treating gastric cancer of young persons by various
      surgical methods. METHODS: 89 young patients with gastric cancer aged 35 years or
      less were analyzed. RESULTS: The resectable rate was 73.0% (65/89), radical
      resectable rate 48.3% (43/89), and palliative resectable rate 24.7% (22/89). The
      5-year survival rate was 24.7% (22/89) and 48.8% (21/43) for the radical group.
      Biological characteristics included infiltrated, diffused growth, lymph node
      metastasis, female predominance. CONCLUSIONS: The biological behavior of gastric
      cancer in young persons is poor. Early management gastric cancer and radical
      operation combined with complex treatment are essential.

PMID- 11829808
TI  - [Morphological cure of cerebral arteriovenous malformations by endovascular
      therapeutics].
AB  - OBJECTIVE: To sum up the clinical characteristics and typical manifestation by
      analysing clinical materials from total embolized cerebral arteriovenous
      malformations (AVM) via endovascular embolization. METHODS: We reviewed clinical
      and image materials of 50 patients whose cerebral AVM were embolized entirely and
      found the cerebral AVM morphological cure by endovascular embolization after
      studying the size, position, artery supply, therapeutics and follow-up. RESULTS:
      50 patients with cerebral AVM were embolized by endovascular therapy, accounting
      for 17% of all patients. Malformation lesions were medium or small type, with a
      diameter less than 3 cm, 95% of them were located in the tentorium superior.
      Terminal end blood supply was common to AVM and especially medium cerebral artery
      (MCA) or its branches. 97% of the patients were graded III or below by spectzler
      grading system. 70% of them had a history of intracranial hemorrhage and were
      cured by one therapy. CONCLUSIONS: It is a reliable and feasible method for
      morphological cure in cerebral AVM via endovascular therapeutics only, but case
      selection is important, that is, medium or small AVM with single branch terminal
      end blood supply in the tentorium superior.

PMID- 11829809
TI  - [Long-term outcome and relevant factors of thymectomy for myasthenia gravis].
AB  - OBJECTIVE: To evaluate the long-term outcome and relevant factors of thymectomy
      for myasthenia gravis (MG) by analyzing patients data. METHODS: 114 patients with
      MG operated between May 1990 and 1997 were reviewed. The results of operation
      were classified in to 4 grades: remission, improvement (efficiency includes
      remission and improvement), no change, and deterioration. The relativity between
      the long-term outcome and the factors of age, sex, the serum titer of AchR
      antibodies, duration of disease, pathological classification of thymus, modified
      osserman classification, and follow-up period was analyzed by logistic and chi(2)
      test. RESULTS: There were 47 man and 67 women aged from 4 to 72 years. Follow-up
      ranged from 10 to 82 months (mean 42, 8 months). The remission rate was 27.2% and
      the effective rate 67.5%. No patient died in the hospital, and the late-death
      rate was 7.0% (8 cases). CONCLUSION: Long follow-up (over 5 years) is necessary
      for evaluating the results of the treatment. There is no correlation between the
      outcome sex, and the serum titer of AchR antibodies. Associated diseases show no
      influence on the outcome of thymectomy.

PMID- 11829810
TI  - [Diagnostic and surgical experience of secondary syringohydromyelia].
AB  - OBJECTIVE: To analyse the diagnostic and surgical experience in 17 patients with
      secondary syringohydromyelia. METHODS: Physical examination and MRI were carried
      out before operation. Surgical treatments were selected according to their
      different original disorders. RESULTS: In three of 8 patients, intramedullary
      tumors were completely removed, 4 subtotally and 1 partially. Pathological
      examination showed mainly ependymoma. The tumor and syrinx on MRI were shown
      along the central axis of the spinal cord, but this was not the same on other 9
      of the 17 patients with extramedullary disorders, which were treated for their
      original disorders. The syrinx was shrunken in all 5 patients taking MRI for
      countercheck. CONCLUSIONS: The diagnosis of secondary syringohydromyelia mainly
      depends on MRI. Surgical treatment should aim at their original disorders.
      Syringohydromyelia includes two pathological types: hydromyelia and
      syringomyelia. Those secondary to intramedullary ependymoma are mostly
      hydromyelia, which may be caused by expanding of tumor along the central canal of
      the spinal cord.

PMID- 11829811
TI  - [Low-tensioned and "b"-like ileocystoplasty].
AB  - OBJECTIVE: To perfectly solve the urine-kept and urinary problems of the vesical
      cancer patients after vesicoectomy. METHODS: We performed low-tensioned and "b"
      like ileocystoplasty in 16 patients. RESULTS: After the operation, new vesica
      urinaria worked well in keeping and emptying urine-urine through the urethra.
      Residual urine test, chemical test and urography showed that there were no
      disturbance of body water and electrolyte metetabolism, no reterograde urine in
      the ureter, no uracratia, and no damage to renal function. CONCLUSIONS:
      Ileocystoplasty can be used clinically.

PMID- 11829812
TI  - [Nonpalpable testicular masses incidentally discovered by ultrasound].
AB  - OBJECTIVE: To determine the diagnosis and management of impalpable testicular
      masses detected sonographically. METHODS: We analyzed retrospectively the
      sonographic findings and pathologic results of such cases and reviewed related
      literature. RESULTS: In over 600 patients receiving scrotal ultrasound, 14 aged
      on average 42.4 years (14 to 71 years) had 16 impalpable testicular masses, with
      a diameter of 5 to 30 mm (mean 12.1 mm). All masses were predominantly hypoechoic
      except for one appeared hyperechoic and calcified. Pathological examination
      showed 2 seminomas, 2 lymphomas, 2 testicular tuberculoses and cysts
      respectively. The other six were embryonal cell carcinoma, metastatic
      adenocarcinoma, testicular fibrosis, partial infarction, testis abscess, and
      hematoma. Malignant lesions accounted for 42.86% (6/14). In 13 of 14 patients,
      the affected testis was resected, while in 1 the testis spared for frozen
      sectioning revealed a benign cystic lesion. CONCLUSIONS: Ultrasound findings can
      not differentiate malignant from benign in the impalpable lesions, and clinical
      history should be considered. All patients with indefinite diagnosis should
      undergo inguinal exploration and the testis can be spared if intraoperative
      frozen section diagnosis is negative. Ultrasound follow-up should be used only if
      there is a strong evidence of infection or trauma.

PMID- 11829813
TI  - [Expression and significance of MXR7 mRNA in human hepatocellular carcinoma].
AB  - OBJECTIVE: To find out the expression and significance of MXR7 mRNA in human
      hepatocellular carcinoma. METHODS: The (32)P labeled and purified PCR product of
      MXR7 cDNA was taken as probe. MXR7 mRNA expression was detected by Northern blot
      analysis in 30 samples of preoperatively untreated HCC and corresponding
      surrounding non-cancerous hepatic tissue, and 12 normal liver tissues confirmed
      pathologically. RESULTS: The frequency of MXR7 mRNA expression in HCC, the
      corresponding surrounding noncancerous hepatic, and normal liver tissues was
      76.6%, 13.3% and 0, respectively. The frequency of MXR7 mRNA expression in HCC
      without serum AFP elevation and in HCC < 5 cm was 9/10 and 5/6 respectively.
      CONCLUSIONS: MXR7 mRNA over-expression in human HCC is common and MXR7 mRNA may
      be expressed at early stage of HCC and can serve as tumor biomarker for HCC. The
      detection of MXR7 mRNA expression in liver puncture tissues may find small HCC
      without serum AFP elevation in the subclinical stage.

PMID- 11829814
TI  - [The proper opportunity of surgery for rectal cancer after preoperative adjuvant
      chemotherapy].
AB  - OBJECTIVE: To discuss the proper opportunity of surgery for rectal cancer after
      preoperative intra-arterial chemotherapy. METHODS: Preoperative chemotherapy was
      performed on 27 rectal cancer cases at Dukes stage B and C. The therapy comprised
      of arterial infusion of 5-fluorouracil 600 mg/m(2), mitomycin 15 mg/m(2) and
      epirubicin 30 mg/m(2) for one course. Miles' or Dixon's operation was carried out
      7 to 10 days later. The effects of chemotherapy were evaluated. Dynamic changes
      of proliferating cell nuclear antigen (PCNA) expression were studied by
      immunohistochemistry on paraffin-embedded sections. RESULTS: Hematochezia was
      remitted in 19 cases. Histologically, the effects of chemotherapy were considered
      as slight, moderate and marked in 9, 15 and 3 cases, respectively. Side effects
      were slight and recovered in 4 days. There was a high expression of PCNA in
      rectal cancer. On the 7th to the 10th day, proliferating index was significantly
      higher than that of before chemotherapy (46.48 +/- 10.62)%, P < 0.05.
      CONCLUSIONS: Preoperative adjuvant chemotherapy plays a role in the treatment of
      resectable rectal cancer. It is suggested that radical surgery should be carried
      out 5 to 6 days after intra-arterial chemotherapy.

PMID- 11829815
TI  - [Effects of inflammatory infiltration on the formation of abdominal aortic
      aneurysm].
AB  - OBJECTIVE: To explore inflammatory infiltration and its effects on the formation
      of abdominal aortic aneurysm (AAA). METHODS: Immunohistochemical technique was
      used to detect lymphocyte (CD45 positive) and macrophage (CD68 positive)
      infiltration while in situ hybridization was applied to investigate the mRNA
      expression of Matrix Metalloproteinase-9 (MMP-9) in 20 cases of human AAA and 4
      cases of normal human abdominal aortas. RESULTS: Inflammatory infiltration
      occurred in every case of AAA with various degree, and there was a parallel
      tendency between the degree of injury of abdominal aortic elastin and that of
      inflammatory infiltration in AAA. Inflammatory infiltration was not found in
      normal aortas. MMP-9 mRNA was detected in macrophages and lymphocytes in all 20
      cases, in smooth muscle cells in 13, and not in normal abdominal aortas.
      CONCLUSIONS: Inflammatory infiltration attended and enhanced the formation of AAA
      through a complex of sequence of biochemical, cellular and immune events.

PMID- 11829816
TI  - [Disc degeneration and cervical instability].
AB  - OBJECTIVE: To evaluate disc degeneration and segmental instability in the
      cervical spine by comparing the magnetic resonance imaging assessment of disc
      degeneration with conventional plain radiographic evaluation with cervical
      segmental instability. METHODS: Two hundred sixty consecutive patients with
      suspected cervical spine disorders were analyzed for horizontal and angular
      displacements on lateral flexion and extension radiographs and disc degeneration
      on T(2)-weighted magnetic resonance images of the cervical vertebrae. RESULTS: In
      all intervertebral levels, the grade of disc degeneration increased significantly
      (P < 0.01) with age. Cervical instability was identified in 151 segments (14.5%)
      and correlated with Grade 1 and Grade 2 degeneration in the intervertebral discs
      (P < 0.01). CONCLUSIONS: Cervical segmental instability may indicate early
      degeneration of intervertebral disc in the cervical vertebrae.

PMID- 11829817
TI  - [Experimental condition for WST-1 assay of skin viability].
AB  - OBJECTIVE: To investigate a new tetrazoliium salt assay (WST-1) of detecting
      tissue and cells of preserved skin. METHODS: With WST-1, viability of porcine and
      human skin split were assessed. The experimental condition such as dosage of
      agents, thickness of skin split, time of reaction, area of skin split and weight
      of skin split were determined. RESULTS: Optimal experimental condition of skin
      split should be 10 mm diameter and 0.3 mm thick, incubation for 3 hours at 37
      degrees C, and reagent dosage of 20 microl. CONCLUSIONS: As a reagent for
      detecting cell viability, WST-1 is successfully applied to the assessment of skin
      viability.

PMID- 11829818
TI  - [IL-12 gene treatment of hepatocellular carcinoma: experimental study].
AB  - OBJECTIVE: To investigate the inhibitory effects of retrovirus vector containing
      IL-12 gene on hepatoma growth in vivo and to explore a new approach of gene
      therapy to hepatocellular carcinoma (HCC). METHODS: Retrovirus vector containing
      IL-12 gene was constructed and transfected into packaged cell PA317. Positive
      PA317 was injected into the rat which suffered from experimental HCC and its anti
      tumor effects and immunity changes were recorded. RESULTS: The packaged cell
      PA317 containing IL-12 gene could inhibit the proliferation of hepatocellular
      cell line CBRH3. The rats injected at day 1 or 3 can survive permanently, while
      those injected at day 5 or 7 can survive longer than those not injected. However,
      tumor generated in rats injected with blank control or package cells containing
      retroviral vector without IL-12 gene (P < 0.01). CONCLUSIONS: Package cells
      transfected with retroviral vector containing IL-12 either injected to the
      hepatoma tissue locally or given splenic exercises anti-hepatoma effects
      efficiently. The direct intrasplenic injection route is new, safe and effective.

PMID- 11829819
TI  - [Experiment and clinical application of targeting treatment with adriamycin
      magnetic albumin microspheres in human gastric carcinoma].
AB  - OBJECTIVE: To study the pharmacokinetics in experimental animals and observe the
      concurrent anticancer effects in human advanced gastric cancer as an adjuvant
      chemotherapy, when adriamycin magnetic albumin microspheres (ADM-MAM) were
      combined with external static magnetic fields. METHODS: The drug concentration of
      targeting tissues in the animals and the stability of ADM-MAM in human gastric
      juices were determined. Clinical and histopathological changes were observed in
      55 cases of advanced gastric carcinomas after targeting treatment. RESULTS: The
      peak concentrations of the targeting tissue were highest after ADM-MAMs were
      administered for 2 hours and remained at the high level for a long time. ADM-MAM
      maintained its stability in human gastric juices. Targeting treatment improved
      the patients' symptoms, raised the rated of tumor resection, prolonged patients'
      lifetime, and enhanced histopathological effects (P < 0.01). CONCLUSIONS: The
      administration of ADM-MAM combined with the external static magnetic fields is
      effective for targeting location and is of clinical value as a preoperative
      adjuvant chemotherapy for human advanced gastric carcinoma.

PMID- 11829820
TI  - [Co-transplantation of islet and allogeneic testicular cell induced immune
      privilege].
AB  - OBJECTIVE: To induce islet allograft long-term survival through co
      transplantation islet with sertoli cell. METHODS: Testicular sertoli cell was
      prepared by digestion of collagenase, trypsin and Dnase, and cultured for 48
      hours. Purified donor (Wistar rat) islet was co-transplanted with allergic
      sertoli cell, in the absence of systemic immunosuppression. TUNEL (terminal
      deoxynucleotidyl transferase-mediated X-dUTP nick end labeling) was used to label
      the apoptosis of lymphocytes surrounding the islet graft. The SABC method was
      used to label the expression of Fas ligand in co-transplantation. RESULTS: Islet
      co-transplantation with 1 x 10(7) sertoli cell reversed the diabetic state for
      more than 60 days in 100% (6/6) of the chemically diabetic SD recipients. Similar
      grafts consisting of islet alone or islet plus 1 x 10(5)-sertoli cell survived
      only for 5 - 6 days. Apoptosis of the lymphocytes surrounding the islet was quite
      clear. CONCLUSIONS: Co-transplantation islet with FasL(+) sertoli cell induces
      local immune privilege and allows long-term graft survival without systemic
      immunosuppression.

PMID- 11829822
TI  - [The detection and its clinical significance of cancer cells in portal vein blood
      of patients with colorectal carcinoma].
AB  - OBJECTIVE: To study the relation between cancer cells in portal vein blood and
      liver metastasis of colorectal carcinoma. METHODS: The presence of CK20 mRNA was
      investigated by non-isotope RT-PCR in 54 cases. RESULTS: The positive rate of
      CK2O mRNA in portal vein blood was 75.9%. The positive cases were significantly
      correlated with Dukes stage and live metastasis. There was a higher probability
      of liver metastasis in positive cases after operation. CONCLUSIONS: The detection
      of CK20 in portal vein blood may improve the accuracy of clinical staging and
      diagnose liver micrometastasis of colorectal carcinoma.

PMID- 11829821
TI  - [Direct intramuscular injection of pSV-VEGF(165) augments capillaries formation
      in a rabbit model of hindlimb ischemia].
AB  - OBJECTIVE: To investigate an easier and safer clinical method of gene therapy for
      treating arterial ischemic diseases in the lower extremity. METHODS: Recombinant
      plasmid pSV-VEGF(165) constructed in vitro was directly injected into the
      ischemic hindlimb muscles in rabbit models. 30 days after gene transfer, the
      capillary density and the capillary to muscle fiber ratio were determined
      histochemically in the resected samples. RESULTS: The capillary density and the
      capillary to muscle fiber ratio were significantly higher for pSV-VEGF(165)
      transfected group than for control group, particularly increased in the shank of
      the hindlimbs. CONCLUSIONS: Direct intramuscular injection of pSV-VEGF(165) was
      an easier and efficient gene therapy method, and it significantly augmented the
      capillary formation in ischemic limbs.

PMID- 11829823
TI  - [Combined TIPSS with modified Sugiura operation for portal hypertension].
AB  - OBJECTIVE: To evaluate the clinical results of combined TIPSS with modified
      Sugiura operation for portal hypertension. METHODS: 24 patients with portal
      hypertension associated with variceal bleeding and ascites were treated with
      TIPSS and then modified Sugiura operation two weeks later. RESULTS: After
      combined TIPSS with modified Sugiura operation, variceal bleeding ceased and
      ascites subsided. The portal pressure significantly decreased (P < 0.01) and the
      portal blood flowed quickly (P < 0.01). The blood velocity of intrahepatic shunts
      was (132.64 +/- 41.42) cm/s. Direct portal venography showed that coronary vein
      had disappeared. No rebleeding was noted in varices and stenosis in intrahepatic
      shunts. CONCLUSIONS: Combined TIPSS with modified Sugiura operation not only can
      reduce portal pressure and improve portal circulation, but also completely
      interrupt coronary vein and maintain liver function.

PMID- 11829824
TI  - [The value of MR cholangiopancreatograghy in diagnosis of obstructive jaundice].
AB  - OBJECTIVE: To evaluate the diagnostic value of MRCP in finding positions and
      causes of obstructive jaundice. METHODS: Fourty-two patients with obstructive
      jaundice received MRCP examination. All patients were finally onfirmed
      operatively. RESULTS: The correct diagnostic rate of finding obstructive
      positions in MRCP was 100% and the correct rate of finding obstructive causes
      78.57%. MRCP combined with MRI raised the accuracy of diagnosis of obstructive
      causes. (90.48%). All pathogenic changes have their own characteristics.
      CONCLUSIONS: MRCP in diagnosing obstructive jaundice is quite effective and safe
      because of its clear pictures without use of contrast medium and no
      complications.

PMID- 11829825
TI  - [Plasma level of glucagon in cirrhotic patients with portal hypertension during
      operation of portacaval shunts].
AB  - OBJECTIVE: To investigate the plasma level of glucagon in cirrhotic patients with
      portal hypertension during operation of portacaval shunts. METHODS: Plasma level
      of glucagon in the portal venous, peripheral venous and arterial blood in
      cirrhotic patients (n = 16) and control patients (n = 16) was measured by
      radioimmunoassay respectively. RESULTS: The glucagon ratio (pg/ml) of the hepatic
      cirrhosis group before, during after operation 3 days after operation, 7 days
      after operation was observed portal venous blood: (189.2 +/- 58.7) pg/ml, (196.1
      +/- 54.2) pg/ml vs. (101.9 +/- 44.8) pg/ml, (98.2 +/- 34.1) pg/ml (P < 0.01);
      peripheral venous blood (184.1 +/- 48.2) pg/ml, (187.5 +/- 42.8) pg/ml vs. (102.4
      +/- 34.7) pg/ml, (95.2 +/- 24.9) pg/ml (P < 0.01); arterial blood: (186.3 +/-
      51.3) pg/ml, (183.5 +/- 54.2) pg/ml vs. (103.4 +/- 36.3) pg/ml, (93.9 +/- 30.6)
      pg/ml (P < 0.01). The portal vein pressure was positively correlated to the
      plasma level of glucagon in portal venous blood of cirrhosis (r = 0.57, P <
      0.01). CONCLUSIONS: Hyperglucagonemia may be caused by the decreased glucagon
      metabolism in cirrhotic liver and hypersecretion of pancreas and the
      gastrointestinal tract. Hyperglucagonemia may be amended after portacaval shunts.

PMID- 11829826
TI  - [Timing changes of apoptosis and proliferating cells nuclear antigen after intra
      arterial infusion chemotherapy for rectal cancer].
AB  - OBJECTIVE: To investigate the timing changes of apoptosis (APO) and PCNA after
      intra-arterial infusion chemotherapy for rectal cancer. METHODS: Twelve patients
      were subjected to percutaneous arterial femoralis catheterization by Seldinger's
      technique and infusion of anti-cancer drugs: 5-fluorouracil (5-Fu) 600 mg/m(2),
      mitomycin (MMC) C5 mg/m(2) and epirubicin (EDR) 35 mg/m(2). The biopsy of rectal
      tumor tissues was done before chemotherapy, and 24, 48, 72 hours and 7-10 days
      after chemotherapy. Apoptotic cells were examined by terminal-deoxynucleotidyl
      transferase (TdT)-mediated dUTP-fluorescein and labeling. The expression of
      proliferating cells nuclear antigen (PCNA) was detected by immunohistologic
      staining. RESULTS: The apoptosis index (AI) of rectal cancer cells before
      chemotherapy, and 24, 48, 72 hours, and 7-10 days after chemotherapy was 6.84 per
      thousand, 19.53 per thousand, 13.15 per thousand, 11.85 per thousand and 11.86
      per thousand respectively. The PCNA index (PI) was 45.56%, 40.68%, 39. 87%,
      51.28% and 63.75% before and 24, 48, 72 hours, and 7-10 days after chemotherapy.
      CONCLUSIONS: Intra-arterial infusion chemotherapy not only induced apoptosis
      effectively, but also inhibited temporarily tumor cells proliferation in
      patients. The curative surgical treatment should be performed as soon as possible
      after chemotherapy.

PMID- 11829827
TI  - [The application of BTA stat in the diagnosis of bladder tumor and hematuria].
AB  - OBJECTIVE: To analyze the value of the Bard BTA Stat for the diagnosis of bladder
      tumor and hematuria in order to find a new, noninvasive examination method.
      METHODS: BTA Stat, an one step monoclonal antibody immunofluorescence analysis
      that qualitatively detects the presence of bladder tumor associated antigen
      (hCFHrp), was used. 65 patients with hematuria, 71 patients with bladder
      transitional cell carcinoma, and 10 normal people underwent voided urine BTA Stat
      analysis. RESULTS: The specificity of the technique for patients with bladder
      transitional cell carcinoma and hematuria was 84.6% and 31.1% respectively, with
      a sensitivity of 73.7% and 90.0% respectively. CONCLUSIONS: BTA Stat was
      considered a convenient, rapid and noninvasive method in the diagnosis of bladder
      tumor. However, the results were interfered by the presence of erythrocyte in
      urine, infection, urinary lithiasis. This method is proved to be useful in the
      surveillance of bladder tumor.

PMID- 11829829
TI  - [Piezoelectric, electrohydraulic and electromagnetic shock wave lithotripsy for
      lower ureteral stone].
AB  - OBJECTIVE: To treat patients with lower ureteral stones by extracorporeal shock
      wave lithotripsy (ESWL) using piezoelectric, electrohydraulic and electromagnetic
      second lithotriptors. METHODS: Six hundred and three patients were divided into 3
      groups according to the modes of lithotriptors. There were 179 patients in EDAP
      LTO1 piezoelectric group, 294 in JDPN IV electrohydraulic group and 130 in
      Dornier Compact S electromagnetic group. Every group was further divided into 3
      subgroups with 10 mm, 10 - 15 mm and 15 mm in diameters of stones. RESULTS: The
      stone-free rate in single session of ESWL was higher in the electromagnetic group
      than in the other two groups. The efficiency quotient was lower in piezoelectric
      group than in the electrohydraulic and electromagnetic groups. The stone-free
      rate in single session was achieved in more than 70% of stones less than 15 mm in
      diameter for electromagnetic and electrohydraulic ESWL. CONCLUSIONS: The overall
      results of electromagnetic and electrohydraulic ESWL on lower ureteral stones are
      better than those of piezoelectric ESWL, and ESWL is suitable for stone less than
      15 mm in diameter.

PMID- 11829828
TI  - [The effect of combined endocrine therapy on prostate and testis].
AB  - OBJECTIVE: To study the pathological changes of the effect of combined endocrine
      therapy on normal prostate, benign prostatic hyperplasia, prostatic
      adenocarcinoma and testis. METHODS: 11 radical prostatectomy specimens, 3 core
      needle biopsies of prostate and 3 testes obtained after at least 3 months of
      enatone-flutamide inhibition therapy were studied. Step-section was performed on
      radical specimens and average 16 sections per case were reviewed. PSA, PSAP and
      AE1/AE3 were immunostained on 14 cases of prostate cancer and a comparative study
      pre- and post-treatment was made. RESULTS: No residual tumor was recognized in 2
      cases. Such characteristic changes were found in 9 cases as prominent acinar
      atrophy, decreased ratio of acini to stroma, stromal fibrosis, squamous
      metaplasia of carcinoma, cytoplasmic vaculation, nuclear shrinkage, and nucleolar
      shrinkage. No apparent change was discovered in 3 cases. Secretory epithelial
      atrophy and basal cell hyperplasia were the popular change in BPH and normal
      prostate. The expressions of both PSA and PSAP were markedly reduced in prostate
      carcinoma and nonneoplastic glands. Pathological downstaging of the tumor was not
      found statistically. Epithelial atrophy also existed in seminal vesicles and
      Leydig cells of the testes after hormone therapy. CONCLUSIONS: Combined endocrine
      therapy results in histologically distinctive changes that can be found in both
      nonneoplastic and neoplastic prostate tissue. However, the drugs can not
      eradicate prostate cancer completely. Testis atrophy is the direct action of the
      therapy.

PMID- 11829830
TI  - [Early use of Chinese drug rhodiola compound for patients with post-trauma and
      inflammation in prevention of ALI/ARDS].
AB  - OBJECTIVE: To evaluate the effects of the Chinese drug rhodiola on the preventive
      treatment of acute lung injury (ALI) caused by post-traumatic/inflammatory and
      thoracic-cardiovascular operations. METHODS: 104 patients who coincide with their
      diagnosis and standard scale were divided randomly in to single number groups
      A(1), B(1), C(1) and D(1) (early preventive treatment group EG) and double number
      groups A(2), B(2), C(2) and D(2) (control group CG). The treatment of primary
      disease both in EG and CG was similar, but in EG four grams of rhodiola compound
      (RCO) were used every day for a period of 3-15 days since admission and 5-7 days
      after operation. The indicators related to ALI in each groups were measured.
      RESULTS: PaO(2), AaDO(2) and hemorheology were significant in EG than in CG (P <
      0.05) or (P < 0.01). The complication rate of ARDS was decreased about of 50.0%
      in EG than in CG. CONCLUSIONS: Early use of RCO may protect against major risk
      factors of ALI/ARDS caused by massive trauma/infection and thoracic-cardio
      operations.

PMID- 11829831
TI  - [Surgical treatment of ventricular septal defect in infants: report of 230
      cases].
AB  - OBJECTIVE: To review the experience of surgical treatment of ventricular septal
      defect (VSD) in infants. METHODS: 230 infants with VSD of less than 3 years old
      underwent surgical repair from Feb. 1990 to Dec. 1997. Their ages ranged from 3
      to 36 months. Their weight was 3.2 to 15.5 kg. The number of patients with
      perimembranous VSD was 192, and that of subpulmonary VSD 36. Two patients had
      multiple VSDs. 150 patients (65.2%) had moderate or severe pulmonary hypertension
      before operation. RESULTS: Thirteen patients died during hospitalization period,
      with a hospital mortality of 5.65%. The main causes of death were pulmonary
      hypertensive crisis and arrhythmia. The leading complications were pulmonary
      infections, arrhythmia and pulmonary hypertensive crisis. CONCLUSIONS: Surgical
      treatment of VSD in infancy may have a satisfactory outcome, it standardized
      surgical techniques and the improved perioperative management are used.

PMID- 11829832
TI  - [Minimally invasive approach for heart valve replacement: report of 73 cases].
AB  - OBJECTIVE: To report a new minimally invasive approach for heart valve operation.
      METHODS: Through right minimal vertical infra-axillary thoracotomy incision (by
      intercostal space), 68 patients with rheumatic heart disease, 2 patients with
      subacute endocarditis, and 3 patients with congenital heart disease underwent
      heart valve replacement from March 1997 to Spring 1998. RESULTS: 30 double valve
      replacements, 33 mitral valve replacements, 10 aortic valve replacements and 14
      DeVega tricuspid annuloplasty were performed. The length of the incision averaged
      (8.5 +/- 0.9) cm, arrest times averaged (88.6 +/- 33.8) min, cardiopulmonary
      bypass times averaged (117.0 +/- 45.9) min. Five mitral valve replacements were
      performed with ventricular fibrillation. Ventilator periods averaged (9.6 +/-
      3.6) h, chest tube drainage averaged (264.5 +/- 184.3) ml. One patient died of
      cerebral bleeding in hospital. Two patients suffered SBE and one of them died.
      The results of follow up for other patients were fine. CONCLUSIONS: This
      minimally incisive valve operation is a new safe, small wounded and cosmetic
      approach for heart valve replacement.

PMID- 11829833
TI  - [Microsurgical treatment for meningioma of falco-tentorial junction].
AB  - OBJECTIVE: To study the clinical characteristics, neuroimaging presentations,
      operative warming events and the results of surgical treatment of meningioma of
      the falco-tentorial junction. METHODS: The clinical data of 14 patients with
      meningioma of the falco-tentorial junction were retrospectively analysed.
      Preoperative examinations included head CT in all patients, DSA in 10, MRI in 6,
      and MRA in 2. 10 patients was operated on via suboccipital transtentorial
      approach, of which, operated-side-up position in 7 patients, three-quarter prone
      operated-side-down position in 3. Three 3 patients was operated on via trans
      infratentorial-supracerebellar approach. One via trans-lateral-ventricle trigone
      approach. RESULTS: Of 14 patients, 12 received total removal of meningioma and 2,
      subtotal resection. Intracerebral hematoma occurred postoperatively in 2 patients
      and, intratumoral-residual-cavity hematoma in 1. Two patients' hematomas were
      eliminated, and another patient's hematoma was conservatively treated. Average
      follow-up period was 4.5 years. All patients resumed their normal work and study.
      One patient had permanent homonymous hemianopsia, and one had trochlear
      paralysis. CONCLUSIONS: Meningiomas of the falco-tentorial junction were
      operable. With some acceptable morbidity, perfect surgical results can be
      obtained.

PMID- 11829834
TI  - [Effect of anti-vascular endothelial growth factor antibody on the progression of
      human gastric cancer orthotopic xenotransplanted into nude mice].
AB  - OBJECTIVE: To study the inhibiting effect of anti-vascular endothelial growth
      factor (VEGF) on the growth and metastasis of gastric cancer. METHODS: The anti
      tumor and anti-metastasis effect of anti-VEGF antibody, mitomycin C (MMC) were
      investigated by means of an orthotopic xenotransplanted model of human gastric
      cancer SGC-7901 in nude mice which had been randomly divided into 4 groups:
      control group receiving PBS, group receiving 50 microg/mice anti-VEGF antibody,
      group receiving 2 mg/kg MMC, and group receiving 50 microg/mice anti-VEGF
      antibody combined with 2 mg/kg MMC. Anti-VEGF antibody was given i.p. twice a
      week and MMC was administered i.p. once a week for 8 weeks from day 7 after
      transplantation. All animals were sacrificed at the end of 10 weeks. The tumor
      was weighted and the intra-tumoral microvessel density (MVD) was recorded, and
      the liver was histologically examined in order to discover micrometastasis.
      RESULTS: Both anti-VEGF antibody and MMC showed a significant inhibitory effect
      on the growth of primary tumors; in the combination treatment group the
      inhibitory effect was more significant than single agent. Liver metastasis
      developed in 19 of 28 mice (67.9%) of the controls and in 6 of 11 mice (54.5%)
      receiving MMC. In contrast, liver metastasis occurred in 2 of 10 mice (20%)
      receiving anti-VEGF antibody and none receiving combination treatment. In
      addition, the MVD was less significant in the anti-VEGF antibody group and
      combination treatment group than other groups. CONCLUSIONS: Anti-VEGF may provide
      a new approach to the treatment of gastric cancer by inhibiting tumor
      angiogenesis, and combination of anti-VEGF antibody with MMC could be more
      effective.

PMID- 11829835
TI  - [Dose-effect of inhaled nitric oxide on pulmonary hypertension in inhaled injury
      in rabbits].
AB  - OBJECTIVE: To explore the relation of dose-response of NO inhalation in treatment
      of pulmonary hypertension in rabbits with smoke inhalation injury. METHODS: The
      effect of various concentrations (1, 5, 10, 20, 30, 40, 50 and 60) x 10(-6) of NO
      on pulmonary hypertension after smoke inhalation injury was studied with right
      heart catheterization in 15 rabbits. RESULTS: Mean pulmonary artery pressure
      (mPAP), pulmonary capillary wedge pressure (PCWP), pulmonary minute vessel
      pressure (Pmv), and pulmonary vascular resistance (PVR) were not changed
      remarkably (P > 0.05) after inhalation of (1 or 5) x 10(-6) NO. mPAP, PCWP, and
      Pmv were lowered significantly after inhalation of (10, 20, 30, 40, 50 and 60) x
      10(-6) NO (P < 0.05, P < 0.01). Major vascular relaxation occurred when NO
      concentration was at 30 x 10(-6), and PVR did not further decrease along with the
      increase of NO concentration. CONCLUSION: The concentration of inhaled NO should
      not exceed 30 x 10(-6) for the treatment of pulmonary hypertension in early stage
      of smoke inhalation.

PMID- 11829836
TI  - [Biopterin synthesis and GTP cyclohydrolase I mRNA expression in rats following
      endotoxic shock].
AB  - OBJECTIVE: To investigate the potential role of changes in biopterin
      (tetrahydrobiopterin and more oxidized species) synthesis and GTP cyclohydrolase
      I (GTP-CHI) mRNA expression in endotoxic shock. METHODS: SD rats were subjected
      to endotoxic shock by a bolus injection of lipopolysaccharide (15 mg/kg, i.p.),
      biopterin and GTP-CHI mRNA levels in liver, kidney, and intestine were determined
      at 4, 8 hours following endotoxin challenge. RESULTS: Tissue biopterin levels
      significantly elevated in liver, kidney, and intestine, with high levels
      sustaining for 8 hours after endotoxin challenge (P < 0.05, P < 0.01). Similarly,
      GTP-CHI mRNA induction in various tissues substantially increased within 4 hours
      compared to normal controls (P < 0.05, P < 0.01). It was also shown that hepatic
      and renal biopterin levels were positively correlated with glutamic pyruvic
      transaminase (GPT) and also blood urea nitrogen (BUN) values (both P < 0.01). In
      addition, treatment with recombinant bactericidal/permeability increasing protein
      (rBPI(21)) markedly reduced tissue biopterin and GTP-CHI mRNA levels, concomitant
      with significant decreases in GPT, BUN as well as D-lactate values. CONCLUSIONS:
      Biopterin synthesis and release may be involved in the development of endotoxin
      induced multiple organ dysfunction, and early use of rBPI(21) is effective to
      inhibit marked GTP-CHI mRNA expression and biopterin formation following septic
      shock.

PMID- 11829837
TI  - [Gene expression of lipopolysaccharide receptor CD14 and tumor necrosis factor
      alpha in rats after thermal injury].
AB  - OBJECTIVE: To investigate changes in lipopolysaccharide receptor CD14 and tumor
      necrosis factor-alpha (TNF-alpha) gene expression in vital organs, and their
      significance in the pathogenesis of systemic inflammation after burns. METHODS:
      Wistar rats were subjected to a 35 percent full-thickness scald injury, then
      sacrificed pre-burn, and postburn 12, 24, 48, 72 hours, respectively. Tissue
      samples from liver, kidney, lung and intestine were collected to measure CD14 and
      TNF-alpha mRNA expression. Peritoneal macrophages were harvested by peritoneal
      lavage to determine CD14 mRNA expression. RESULTS: CD14 mRNA expression increased
      markedly after thermal injury, peaking at both 12 and 48 hours. Likewise, CD14
      mRNA levels were significantly up-regulated in peritoneal macrophages. Gene
      expression of TNF-alpha elevated markedly in liver, lungs, and kidneys after
      acute insults. Positive correlation was found between CD14 mRNA and TNF-alpha
      mRNA in liver, lung, and kidney tissues. CONCLUSIONS: Thermal injury per se can
      markedly up-regulate both CD14 and TNF-alpha gene expression in various organs.
      Excessive CD14 mRNA expression may enhance synthesis and release of TNF-alpha
      stimulated by endotoxin translocation, and the interaction between CD14 and TNF
      alpha may play an important role in mediating multiple organ damage secondary to
      major burns.

PMID- 11829838
TI  - [Effect of dietary arginine supplementation on wound healing and the relationship
      between dose and response in burn rats].
AB  - OBJECTIVE: To examine the dose-effect of dietary L-arginine supplementation on
      burn wound healing. METHODS: The effect of dietary L-arginine supplementation was
      studied in rats with deep thickness burn (10% TBSA). The time for epithelization
      of burn wound was determined. Photography of burn wound was taken for measuring
      percentage of burn wound healing area. Biopsies of burn wound were taken for
      measuring the content of hydroxyproline, the ratio between type I and type III
      collagen, and dermal cell cycle. RESULTS: Supplemental dietary L-arginine after
      burn in rats shortened the time for epithelization of burn wound, increased the
      content of hydroxyproline, decreased the ratio between type I and type III
      collagen, elevated the DNA content of dermis. Supplemental dietary L-arginine in
      the dose of 200 mg x kg(-1) x d(-1) was more effective than any other, 50 mg x
      kg(-1) x d(-1) and 800 mg kg(-1) x d(-1) showed no beneficial effect on the
      healing of burn wound. CONCLUSIONS: Suitable L-arginine supplementation can
      enhance burn wound healing in rats.

PMID- 11829839
TI  - [Monitoring of bacteria resistance in burn patients].
AB  - OBJECTIVE: To monitor the bacteria resistance in burn patients. METHODS: Disk
      susceptibility tests were performed and interpreted according to the NCCLS
      criteria. Four kinds of the third generation cephalosporins extended-spectrum
      beta-lactamase produced by multi-resistant of P. aeruginosa and K. Pneumoniae
      strains were detected after 20 microgram of sulbactam was added respectively, in
      contrast to no sulbactam. RESULTS: 227 strains were isolated from burn patients.
      195 strains (86%) were gram-negative bacteria. Disk susceptibility showed various
      bacteria had high antibiotic resistance and multi-resistant rate. S. aureus was
      only susceptible to vancomycin, its resistant rate to imipenem was 19%. P.
      aeruginosa was only susceptible to polymyxin-B, its resistant rate to ceftazidime
      was 20%. However, after stop using ceftazidime two years, the susceptibility to
      gram-negative bacteria recovered. The resistant rate of ceftazidime to P.
      aeruginosa, E. coli, K. pneumoniae were decreased respectively. The resistance to
      quinolones was increased. The resistant rate of ciprofloxacin to P. aeruginosa,
      K. pneumoniae was increased respectively. After 20 microgram sulbactam added to
      cephalosporins drug disks, the primary susceptibility of ceftazidime to P.
      aeruginosa and K. pneumoniae recovered, and the antibiotic was better than the
      other cephalosporins. CONCLUSIONS: It is important to monitor the bacteriology in
      burn patients at all time, and understand the changing pattern of bacterial
      flora, antibiotic susceptibility and bacterial strains spreading in burn ward.
      Extended-spectrum beta-lactamases is the cause of resistance. After sulbactam
      added to the third generation of cephalosporins, the beta-lactamases were
      inhibited, and the susceptibility of antibiotics to bacteria were increased and
      ceftazidime was prior to others.

PMID- 11829841
TI  - [The relationship of lung function and heart function of RHD patients in
      different period].
AB  - OBJECTIVE: To investigate the relationship of heart function and lung function in
      RHD patients. METHODS: We compared heart posterior-anterior film, lung function
      test results, PaO(2) and O(2) Sat of blood gas analysis before and after motion
      before operation, early postoperation, late postoperation, according to heart
      function and cardiothoracic ratio in 98 RHD patients. RESULTS: With worsening of
      heart function and enlargement of cardiothoracic ratio, lung function worsened
      too. PaO(2) and O(2) Sat did not change apparently. The lung function of early
      postoperation did not improve significantly. The lung function improved gradually
      with better heart function and shortening of heart in later postoperation. But
      small air way obstruction and diffuse function and function residue volume
      changed slowly. CONCLUSIONS: Heart function affects the lung function directly.
      They were positively correlated.

PMID- 11829840
TI  - [Clinical application of expandable metal stent for palliation of malignant
      biliary obstruction].
AB  - OBJECTIVE: To investigated the long-term result of expandable metallic biliary
      stent implantation and evaluated preliminarily the factors that might impact the
      therapeutic effectiveness. METHODS: 134 patients with malignant choledochal
      stenosis were treated with metallic endo-prosthesis (128 transpapillary
      endoscopically and 6 transhepatic percutaneously). The follow-up results were
      compared with those of 97 patients with conventional plastic stents during the
      same period. RESULTS: The success rate was 95.7%, and the procedure related
      complications were found in 6.4% of patients. The jaundice was eliminated
      completely in 85.6% patients. During long-term follow-up, the metal stents were
      shown patent for a mean duration of 300 days, which was significantly longer than
      80 days of polyethylene endoprostheses (P < 0.01). The mean survival was 210
      days. From classified data assessment, the stent patency in primary bile duct
      neoplasm group was almost similar to that in metastatic group, but the median
      survival of the former was slightly longer than that of the latter. There were
      flow differences in patancy and survival rates between the hilar obstruction
      group and the middle and low obstruction group. CONCLUSIONS: The median patancy
      of expandable metal stents was significantly longer than that of conventional
      plastic prostheses. To get the highest benefit, however, the indication should be
      strictly selected.

PMID- 11829842
TI  - [Neuronavigation for the resection of intracranial cavernous angiomas].
AB  - OBJECTIVE: To evaluate the use of the Stealth Station neuronavigator in
      conjunction with preoperative computerized tomography (CT) in the resection of
      intracranial cavernous angiomas (CAs). METHODS: The Stealth Station
      neuronavigator was used to provide real-time correlation of the operating field
      and computerized images in 6 patients with CAs. All of them suffered from
      epileptic seizures. RESULTS: Neuronavigation-guided lesionectomy with removal of
      hemosiderin deposition, gliosis and calcification in all cases was performed
      precisely. Mean fiducial error, predicted accuracy at 10 cm, and sustained
      accuracy ranged from 1.65 to 4.53 mm, 1.82 to 3.28 mm, and 0.50 to 3.45 mm,
      respectively. CONCLUSIONS: The Stealth Station neuronavigator is reliable and
      accurate in the resection of CAs.

PMID- 11829843
TI  - [Correlation between gene expression of CCK-A receptor and gallbladder emptying
      in gallstone patients].
AB  - OBJECTIVE: To investigate the expression of CCK-A receptor and its relation with
      gallbladder hypomotility in patients with gallstone. METHODS: 20 patients with
      gallstone and 10 normal subjects were studied and gallbladder emptying function
      was measured by B ultrasonography. The other 8 patients without gallstone who
      died of accident were selected as controls for measuring mRNA expression of CCK-A
      receptor of gallbladder; RT-PCR was used to explore gene expression of CCK-A
      receptor of gallbladder. RESULTS: The gallbladder motility was significantly
      impaired in gallstone patients. The patients had lower mRNA expression of CCK-A
      receptor than control subjects (0.633 +/- 0.167 vs. 0.944 +/- 0.230, P < 0.01),
      and so did patients with impaired gallbladder motility then those with normal
      motility (0.544 +/- 0.124 vs. 0.768 +/- 0.131, P < 0.05). Furthermore, the change
      of expression of CCK-A receptors was markedly correlated with gallbladder
      emptying (r = 0.925, P < 0.01). CONCLUSIONS: mRNA expression of CCK-A receptor in
      gallstone patients decreases, which was related to gallbladder hypomotility. The
      down-regulation of gene expression of CCK-A receptor plays an important role in
      gallbladder hypomotility in patients with gallstone.

PMID- 11829844
TI  - [Sex hormone receptor of hemangioma and vascular malformation in children].
AB  - OBJECTIVE: To investigate the level and difference of estrogen receptor (ER),
      progestogen receptor (PR) and androgen receptor (AR) in hemangioma tissues of
      Children. METHODS: 31 specimens of hemangioma and 36 specimens of vascular
      malformation were compound stained with hematoxylin-eosin and enzyme-linking
      affinitive immunohistochemistry. The prepared tissue slices were examined
      microscopically to find the ER, PR and AR in all the cells. RESULTS: The ER, PR
      and AR were detected in the two kinds of the tissue. However, their levels in the
      hemangioma were higher than those in the vascular malformation (P < 0.01) and the
      levels in the hemangioma of proliferating phase were higher than those in the
      hemangioma of regressive phase (P < 0.01). CONCLUSIONS: Hemangioma is one of the
      target tissues of estrogen. ER, PR and AR play an important role in the growth
      and development of hemangiomas. The binding site of the receptor may be occupied
      by extrogenous glucocorticoid so that hemangiomas gradually degenerates.

PMID- 11829845
TI  - [Lactulose mannitol ratio in patients after operation].
AB  - OBJECTIVE: To study lactulose (lactulose, L) and mannitol (mannitol, M) ratio in
      urine following operation and investigate the correlation between severity of
      stress and L/M ratio. METHODS: 20 patients who had received operation were
      enrolled and each patient was evaluated by APACH II scores. L/M permeability
      study was performed before the operation and 5 and 10 days after the operation.
      The L and M concentration was analyzed by HPLC with pulsed electrochemical
      detection (HPLC-PED). The correlation between L/M ratio and the severity of
      surgical stress were related. RESULTS: The L/M ratio before the operation was
      (0.023 +/- 0.002), increased to (0.042 +/- 0.005) in the 5th post-operative day
      (P < 0.01), and then returned to (0.024 +/- 0.002) (P > 0.05) compared with pre
      operation in the 10th Post-operation. A significant correlation between the
      severity of stress and the L/M ratio was observed (r = 0.762). CONCLUSIONS: The
      L/M ratio was increased 5 days after the operation and the L/M ratio was
      correlated with severity of operative stress.

PMID- 11829846
TI  - [Biomechanical evaluation of five fixation techniques for the lower cervical
      spine].
AB  - OBJECTIVE: This study biomechanically investigated the three-dimensional motion
      stability of five reconstruction methods in the cervical spine, in order to
      provide the biomechanical basis for the clinical selection of fixation methods.
      METHODS: With eight adult cervical spine fresh specimens, the three-column injury
      was produced at C(4 - 5) level. The spinal constructs, reconstructed by various
      techniques including anterior titanium locking screw plate (TLSP), posterior
      interspinous wiring (IW), combined fixation with the TLSP and IW (TLSP + IW), Roy
      Camille plate (RP), and transpedicular screw plate (TP), were tested under six
      loading modes-flexion, extension, right/left lateral bending, and right/left
      axial rotation. RESULTS: The three-dimensional motion stability of either TLSP or
      IW was less than that of intact cervical spine. The TLSP + IW and RP provided
      increased stability compared with the intact spine. The stabilizing capabilities
      of transpedicular screw plate fixation was the best in all loading modes.
      CONCLUSIONS: In three-column instability of cervical spine injury, exclusive use
      of the anterior plate or the posterior interspinous wiring was not supported by
      the results. The stabilizing capabilities provided by combined anterior and
      posterior instrumentation and posterior plate were good. The three-column
      fixation for the cervical spine using transpedicular screw plate fixation offers
      increased stability significantly over that of other conventional cervical
      fixation systems.

PMID- 11829847
TI  - [The diagnostic value of perforin and granzyme B genes mRNA expression in acute
      rejection after hamster to rat orthotopic liver transplantation].
AB  - OBJECTIVE: To explore the mRNA expression of perforin and granzyme B genes
      activated by cytotoxic T lymphocytes (CTL) for monitoring early acute rejection
      after liver transplantation. METHODS: The mRNA expression of perforin and
      granzyme B genes in grafts after gold hamster to rat liver transplantation was
      examined by reverse transcriptase polymerase chain reaction. Histological
      findings were studied comparatively, and isogenic rat liver transplantation was
      the control. RESULTS: The mRNA expression of perforin and granzyme B genes began
      to be up-regulated on the day 3 after transplantation, when no histologic
      evidence of rejection was found. Levels of expression significantly increased
      after day 4 and persisted through the whole course of rejection. In contrast, the
      control group showed no expression of mRNA for perforin and granzyme B.
      CONCLUSIONS: The determination of mRNA expression of perforin and granzyme B
      genes are useful to early diagnosis of acute rejection of liver transplantation.

PMID- 11829848
TI  - [The effects of moderate acute normovolemic hemodilution on intestinal oxygen
      supply and consumption in anesthetized cats].
AB  - OBJECTIVE: To study the effects of moderate acute normovolemic hemodilution on
      the intestinal blood perfusion and oxygen supply in cats. METHODS: 15 domestic
      male cats were hemodiluted with Haemaccel. HR, MAP, lactate concentration in
      superior mesenteric vein (LAC), superior mesenteric artery blood flow (SMABF),
      superior mesenteric artery and venous blood gas analysis were recorded and the
      intestinal oxygen delivery (DO(2)), oxygen consumption (VO(2)) and oxygen
      extraction (EO(2)) were calculated before and after hemodilution. RESULTS: SMABF
      increased obviously (P < 0.05), intestinal DO(2) and EO(2) did not change (P >
      0.05) but VO(2) increased (P < 0.05), and LAC in superior mesenteric vein did not
      increase. CONCLUSIONS: Moderate acute normovolemic hemodilution with Haemaccel do
      not alter intestinal oxygen delivery by increasing the superior mesenteric blood
      flow. It means that intestinal mucosa ischemia does not happen during moderate
      acute normovolemic hemodilution.

PMID- 11829849
TI  - [Histology and physiological function of dogs after extirpation of bronchi].
AB  - OBJECTIVE: To investigate the effect of extirpation of bronchi on histology and
      physiological function. METHODS: 21 dogs were divided in to two groups: control
      (3) and experimental (18). After bronchi extirpation one week, two weeks, one
      month, three months, six months, and twelve months, we used specimens to test the
      pulmonary surfactant (PS) and to observe the morphological changes. RESULTS:
      After the operation, the residual lung nearby the operative area had traumatic
      changes. Around the aforementioned area, the structure of lung was normal.
      Specially after six months, the lung returned to good status. We found that two
      weeks after operation, the contents of PS increased remarkably (P < 0.05). After
      one month the parameter returned to normal (P > 0.05). CONCLUSIONS: The residual
      lung after bronchi extirpation had ventilation and air-exchange functions. The
      lung function was preserved directly.

PMID- 11829850
TI  - [Diagnosis and treatment of familial adenomatous polyposis].
AB  - OBJECTIVE: To summarize the experience with diagnosis and therapy of familial
      adenomatous polyposis (FAP). METHODS: Thirteen patients with FAP who had
      undergone total colectomy were analyzed retrospectively. RESULTS: In 5 patients
      with benign and 8 patients with malignant adenomatous polyposis, their average
      age at operation was 31.5 years (range 10 - 57), 25 years in benign patients and
      36 years in malignant patients. Familial inherited histories were found in 8
      patients in 6 families. Nineteen patients were determined in 6 families in 3
      generations. Seven familial members died of colorectal cancer in 4 families.
      History lasted 2 - 20 years. The number of adenomatous polyposis was more than
      100. All patients underwent total colectomy, ileostomy or anus-preserving surgery
      with or without ileal pouch. All patients without canceration survived. The
      longest one exceeded 25 years, but 3/8 patients with canceration developed
      metastasis of liver, brain and abdomen within 6 months after surgery.
      CONCLUSIONS: FAP will turn to be cancer if not removed. Total colectomy or
      proctocolectomy should be performed before canceration. Total colectomy,
      preserving muscular sheath of the rectum after mucosectomy, ileal pouch-anal
      anastomosis may be the operative choice for FAP.

PMID- 11829851
TI  - [The relationship between operation on gastrointestinal cancer and single cells
      metastasis via portal vein].
AB  - OBJECTIVE: To confirm the effect of radical operation on single cells metastasis
      of gastrointestinal cancer. METHODS: One hundred and seventy two patients with
      gastrointestinal cancer were divided randomly into group I (111 cases, ordinary
      operation) and group II (61 cases, operation after ligation of drained vessels).
      Catheters were inserted into the portal vein during operation. Blood was
      aspirated and contrifugated. Anti-EMA monoclonal antibody marked the cancer
      cells, which were shown by ABC immunohistochemical staining. RESULTS: In the
      examinate group, 72 cases of gastrointestinal cancer were found positive cells
      among 111 cases (positive rate 64.9%). In the control group, 61 cases were tested
      and 13 cases were found positive cells (positive rate 21.3%) with a highly
      significant difference between the two groups (P < 0.005). CONCLUSIONS: Ligating
      the relative blood vessel before the radical operation can prevent single cancer
      cells from metastasis via portal vein.

PMID- 11829852
TI  - [Preoperative arterial infusion chemotherapy of colorectal carcinoma pathological
      and clinical effects].
AB  - OBJECTIVE: To investigate the pathological and clinical effects of preoperative
      selective intra-arterial infusion chemotherapy on colorectal carcinoma. METHODS:
      30 patients with colorectal carcinoma underwent selective regional arterial
      angiography by Seldinger's method followed by intra-arterial infusion
      chemotherapy. RESULTS: changes of karyopyknosis, karyorrhexis, coagulation and
      necrosis of cytoplasm in cancer cells around vascular vessels were found in all
      cases. Interstitial edema, invasion of inflammatory cells, fibroelastosis around
      cancer cells, proliferous intima, thrombus and inflammation of vessels were also
      found at the same sites. CONCLUSIONS: Histological changes are significant after
      preoperative selective intra-arterial infusion chemotherapy for colorectal
      carcinoma. This therapy can relieve symptoms.

PMID- 11829853
TI  - [Liver metastasis in colorectal cancer and tumor angiogenesis].
AB  - OBJECTIVE: To investigate the association between tumor angiogenetic activity and
      metastatic potential of colorectal cancer (CRC) retrospectively. METHODS: The
      microvessel density (MVD) and the level of vascular endothelial growth factor
      (VEGF) expression were examined immunohistochemically from 61 specimens obtained
      by surgical resection of CRC. RESULTS: MVD was (27.0 +/- 8.4) and the expression
      of VEGF was (59.75 +/- 12.36)%. Both were significantly higher in the group of
      liver metastasis, and in the group of lymph node metastasis (P < 0.01, P < 0.05).
      Survival analysis indicated a significant difference between increasing MVD group
      and the control group (P < 0.01). CONCLUSIONS: VEGF-mediated angiogenesis plays
      an important role in liver metastasis of CRC, and MVD appears to be a new
      prognostic factor for the prediction of outcome in patients with CRC.

PMID- 11829854
TI  - [The accessory diagnosis of rectal carcinoma by ICM and oncogene expressions].
AB  - OBJECTIVE: To enhance the diagnostic accurate rate of preoperative biopsy on
      rectal carcinoma. METHODS: The paraffin embedded biopsy tissues of 17 cases of
      preoperatively unconfirmed rectal carcinoma and 15 cases of normal rectal mucosa
      (control group) were examined by routine pathology, image cytometry (ICM), and
      the expressions of protein products of oncogene p53 and ras. RESULTS: In the
      experimental group, 53% specimens were classified as non-diploid by ICM, and the
      positive rates of p53 and ras expressions were 71% and 47% respectively. The
      positive rates were higher than those of routine pathology and the differences
      were significant. In the control group, the results of ICM and oncogene
      expressions were negative. In the experimental group, there were 11 cases of
      atypical hyperplasia and 5 cases of chronic inflammation only. Non-diploid, and
      positive expressions of p53 and ras were found in 8, 11 and 7 cases of atypical
      hyperplasia respectively; however, they were all negative in chronic
      inflammation. The differences between atypical hyperplasia and chronic
      inflammation were significant. ICM was correlated well with expressions of p53
      and ras oncogene. CONCLUSIONS: The techniques of ICM and detecting the
      expressions of protein products of oncogene p53 and ras can be a supplementary
      tool for routine pathology to improve the diagnostic rate of rectal carcinoma.

PMID- 11829855
TI  - [The action of proglumide blocking gastrin on gastric cancer cells].
AB  - OBJECTIVE: To investigate the practicability of proglumide to treat gastric
      cancer. METHODS: MKN45 gastric cancer cell line was cultured and the effects on
      gastrin and gastrin receptor antagonist proglumide proliferative rate, cell
      dynamic cycle distribution and the concentration of cAMP in the cells were
      observed in vitro. RESULTS: Gastrin promoted the proliferation of MKN45 cells and
      shifted cells from phase G(0)/G(1) to phase S, G(2)/M as well as increased
      intracellular cAMP, while proglumide blocked these effects. CONCLUSIONS: Gastrin
      induces the proliferation and synthesis of DNA by its receptor. Proglumide may
      provide a new approach of non-cytotoxic treatment of gastric cancer.

PMID- 11829856
TI  - [Analysis and prevention of reoperation on congenital choledochal cyst].
AB  - OBJECTIVE: To investigate the reasons and prevention of reoperation on congenital
      choledochal cyst (CCC). METHODS: The sex, age, cyst type, timing and method of
      operation were analyzed 22 reoperated (CCC) patients who underwent reoperation.
      RESULTS: The reoperation rate was 24.4% (22/90). The gender age and cyst type
      were not related to reoperation rate (P > 0.05). Reoperation rate was correlated
      with the timing the modality and the manoeuvre of the surgery. The previous
      emergent surgery incurred higher reoperation rate than that of selective
      operation (P < 0.01). The reoperation rate was 88.9% in patients previously
      undergoing CCC extracorporeal drainage, it was 52.4% in group of internal
      drainage and 5.0% in group previously undergoing CCC resection (P < 0.01).
      CONCLUSIONS: Congenital choledochal cyst should be treated by surgery in its
      early stage. Pradent policy should be adopted on the use of PTC and ERCP. Outer
      drainage was used as the first-aid measure; internal drainage should be
      abandoned; resection of the cyst with Roux-Y hepaticojejunostomy should be the
      therapy of choice.

PMID- 11829857
TI  - [One stage surgical repair for complex cranio-orbital injury].
AB  - OBJECTIVE: To approach clinical effect of early stage surgery on complex cranio
      orbital injury. METHODS: Surgical procedures included removal of intracranial
      hematoma, contused and necrotic brain tissues, correction of cranio-orbital
      deformity, and repair of dure mater. RESULTS: Early evaluation was completed in 6
      weeks, and late evaluation was made in 6 months after surgery according to the
      scale of Jennett and Bond's plastic surgical outcome and Glasgow outcome scale
      (GOS). Six weeks after surgery, GOS grade I was observed in 6 patients and GOS
      grade II in 3 patients. Excellent scale of Jennett and Bond was seen in 4
      patients and good scale in 3 patients. Cerebrospinal leakage was effectively
      obstructed in 5 patients. CONCLUSIONS: Early stage repair for complex cranio
      orbital injury may be conducive to improving neural function and decreasing
      intracranial infection.

PMID- 11829858
TI  - [The treatment of 432 patients with pituitary adenomas via transsphenoidal
      approach].
AB  - OBJECTIVE: To study some clinical features of 432 cases of pituitary adenomas
      treated by transsphenoidal microsurgery between July 1982 and October 1996.
      METHODS: Pathological examination, immunohistochemical examination and
      electronmicroscopic examination were done in 424, 29 and 103 cases respectively.
      RESULTS: Hyperprolactinemia was found in many so-called non-functioning adenomas
      besides in prolactinomas. The dura maters were invaded by tumors in 78 cases (the
      incidence of dural invasion was 65.5%). CONCLUSIONS: Hyperprolactinemia is not
      peculiar to prolactinomas, and differential diagnosis is necessary when
      hyperprolactinemia exists. The involvement of the dura mater of sellar floor is
      an important mark that the adjacent tissues were invaded by pituitary adenomas.
      The outcome of surgical treatment is significantly different between the patients
      with dural invasion and without invasion.

PMID- 11829859
TI  - [Long term effect of thymectomy for patients with myasthenia gravis].
AB  - OBJECTIVE: To evaluate the long term effect of thymectomy for patients with
      myasthenia gravis. METHODS: Patients with myasthenia gravis 4 - 54 months after
      thymectomy were followed up. RESULTS: 124 patients with myasthenia gravis were
      treated by thymectomy from April 1990 to August 1994. The mean age at the time of
      surgery was 29.2. According to the modified Osserman classification. 29 patients
      were type I, 23 type II a, 41 type II b and 11 type III. After thymectomy 82.7%
      patients had good response to the operation. 13.5% had no response and 1.9% were
      even worse. Of 104 patients followed up, no early death was found and late death
      occurred in 2. Type II patients and those with shorter preoperative course
      responded better. CONCLUSIONS: The surgical outcome is related to clinical
      classification of myasthenia gravis and the duration of preoperative period. Sex
      and pathologic type of thymus lesion seem to be irrelevant factors to the
      surgical outcome. To perform thymectomy or not should be very carefully weighed
      for patients younger than 10 years of age.

PMID- 11829860
TI  - [Total removal of craniopharyngioma].
AB  - OBJECTIVE: To study the better method of surgical management of craniopharygioma.
      METHODS: We treated 30 patients with craniopharyngioma ranged in age from 15 to
      55 years (mean: 34.13 years old). MR image showed that the tumors' diameter
      varied from 2.0 cm to 6.0 cm (mean, 3.34 cm). 17 patients had the tumor in
      suprasellar region, 11 had tumor extension in the third ventricle 2 and had the
      tumor down to insellar. Complete cystic tumor was seen in 5 patients, partial
      cystic tumor in 17, and solid tumor in 8. Calcified tumor was found in 18
      patients. Frontal temporal craniotomy was performed in all patients. The tumor
      was dissected in the parachiasmal opticocarotid, carotidotentorial spaces and
      lamina terminals. Great attention was paid to the preservation of the perforating
      arteries from the carotid, posterior and anterior communication and anterior
      choroidal arteries to the structure of the hypothalamus. The solid portion of the
      tumor was removed by piecemeal. RESULTS: The tumor was totally removed in 29
      patients and subtotally removed in 1 patient by second surgery. Follow-up showed
      that 27 patients resat normal life, 1 patient needed assistance, 1 died 7 days
      after surgery from inhalation asphyxia, and 1 died from complications of diabetes
      insipidus. CONCLUSIONS: Many different surgical approaches can be used in the
      treatment of carniopharyngioma according to the localization and extension of the
      tumor. However, avoidance of the neural structures injury in the third ventricle
      and preservation of the perforating arteries to hypothalamus are essential to
      achieving a good surgical result.

PMID- 11829861
TI  - [Adrenal cortical carcinoma].
AB  - OBJECTIVE: To study the diagnosis and treatment of adrenal cortical carcinoma.
      METHODS: Fifteen cases of adrenal cortical carcinoma (8 functional and 7
      nonfunctional) were treated surgically during the period of 1978 - 1998. They
      were confirmed operatively and pathologically. RESULTS: The functional carcinoma
      usually showed typical clinical features such as Cushing's syndrome, primary
      aldosteronism, and adrenogenital syndrome. The nonfunctional had extra-adrenal
      symptoms such as acute abdominal pain and hypertension. A definite diagnosis can
      be made by the measurements of urine 17-ketosteroid, 17-hydrosteroid, cortisol,
      aldosterone, CT, and B-ultrasonography. CONCLUSIONS: Surgical removal of the
      tumor is the only effective treatment. Early diagnosis of adrenal cortical
      carcinoma is very difficult, especially in the non-functional.

PMID- 11829862
TI  - [Treatment of benign prostatic hyperplasia with laser through the endoscope].
AB  - OBJECTIVE: To evaluate the effect of transurethral laser prostatectomy (TULP) and
      its relation with the size of prostate. METHODS: 469 benign prostatic hyperplasia
      receiving TULP from 1988 to 1998 were reviewed retrospectively, and the methods
      of operation and preoperative and postoperative symptom were compared. The effect
      of 233 patients undergoing TULP was compared with the size of the prostate.
      RESULTS: The average value for IPSS of 469 patients decreased from 26.7
      (preoperation) to 14.2 (postoperation). The mean value of maximum uroflow rate
      increased from 6.2 ml/s (preoperation) to 11.8 ml/s (postoperation). No
      difference was seen in postoperative effect between the transurethral contact and
      noncontact laser prostatectomy. If the estimating weight of prostate exceeded 50
      g, the maximum flow rate after 3 years was decreased evidently, the value of IPSS
      increased to over 20. CONCLUSIONS: If the estimating weight of prostate is less
      than 50 g, TULP is indicated.

PMID- 11829863
TI  - [Synovial chondromatosis: clinical analysis of 13 cases].
AB  - OBJECTIVE: To study the diagnosis and treatment of synovial chondromatosis.
      METHOD: 13 cases of synovial chondromatosis were studied by pathological
      observation, X-ray examination and clinical research. RESULTS: Intermittent joint
      pain, swelling, limited motion, joint snapping or rubbing were found, sometimes
      with joint interlocking and movable mass in the joint. X-ray showed fewer loose
      bodies than the actual ones in the joint. Rough surface, congestion and
      thickening of synovial membrane at the lesion were found during the operation.
      Proliferation of blood vessels, accumulation of lymphocytes and proliferation of
      synovial superficial cells and fibrous tissue were observed under the microscope.
      The loose body consisted of many tubercles microscopically. CONCLUSIONS: The
      combination of clinical observation, X-ray examination and pathological diagnosis
      is essential to the diagnosis of synovial chondromatosis. Excision of loose body
      and synovial membrane may lead to satisfying results.

PMID- 11829864
TI  - [The levels of renin activity, angiotensin converting enzyme and angiotensin II
      in cirrhotic patients with ascites undergoing portacaval shunt].
AB  - OBJECTIVE: To investigate the changes of plasma renin activity (PRA), angiotensin
      converting enzyme (ACE), angiotensin II and portal venous pressure (PVP) in
      cirrhotic patients with ascites undergoing portacaval shunt. METHODS: Serum PRA,
      ACE, A II levels in portal vein, artery, peripheral vein and PVP were measured in
      16 cirrhotic patients with ascites before and after portacaval shunts and in
      control group of 16 cases of gastrointestinal carcinoma. By light colorimetric
      analysis and radio-immunization assay. RESULTS: PRA, ACE, A II levels and PVP of
      pre- and after portacaval shunt were significantly higher in cirrhotic patients
      than the control group (P < 0.05), and they were significantly decreased after
      the shunt in the cirrhotic patients (P < 0.05). The PVP was in positive
      correlation to the levels of serum ACE in cirrhotic patients (r = 0.48, P <
      0.01). CONCLUSIONS: The levels of serum PRA, ACE, A II and PVP decreased
      significantly in cirrhotic patients with portal hypertension after portacaval
      shunts. It may be major causes of ascites disappearance in cirrhotic patients
      after portacaval shunt.

PMID- 11829865
TI  - [The detection of high risk human papillomaviruses in papillary transitional cell
      carcinoma of urinary bladder].
AB  - OBJECTIVE: To investigate the histological evidence of high risk human
      papillomavirus infection in bladder cancer. METHODS: 52 cases of papillary
      transitional cell carcinoma of the urinary bladder were studied for the
      incorporation of high risk human papillomavirus type 16 and type 18 DNA by non
      isotopic in situ hybridization (NISH). RESULTS: 19 of 52 cases (36.5%) were
      positive for HPV DNA with punctuate and/or diffuse purple-blue staining in the
      nucleus of cancer cells, including two cases positive both for HPV16/18. HPV DNA
      were predominantly expressed in superficial tumors. Among these positive tumors,
      adjacent normal epithelium and Brunn's nests also showed positive staining.
      Morphologically, HPV positive cells existed in the whole layer of papillary tumor
      cells, 3 of them presented koilocytoid change. CONCLUSIONS: HPV infection might
      be a common event in urinary bladder and a potential factor for carcinogenesis of
      bladder cells.

PMID- 11829866
TI  - [Apoptosis of small intestinal epithelial cells in small intestinal allograft
      rejection].
AB  - OBJECTIVE: To investigate apoptosis of epithelial cells during small intestinal
      allograft rejection in rats. METHODS: Heterotopic small intestinal
      transplantation was performed with inbred rat F344/N (RT1(l)) and inbred rat
      Wistar/A (RT1-A(k), RT1-E(d)). All recipients were divided into four groups:
      group I, nonoperative control (Wistar); group II, isograft control (Wistar-
      >Wistar); group III, allograft (F344-->Wistar); group IV, treatment control [F344
      ->Wistar + Cyclosporine A (6 mg x kg(-1) x d(-1))]. The grafts were harvested on
      day 3, 5, 7 after operation. All graft samples were subjected to histological
      examination and apoptotic cells of graft epithelial cells with terminal
      deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL). RESULTS:
      Histologically mild acute rejection occurred on day 3 after operation in group
      III, moderate acute rejection on day 5 after operation, severe acute rejection on
      day 7 after operation. But none of group II had the histological evidence of
      acute rejection and the histological evidence of group IV indicated that
      Cyclosporine A could effectively controlled small intestinal acute allograft
      rejection. The TUNEL showed that the number of apoptotic cells per crypt in group
      III was significantly higher than that of the other three control groups on day 3
      and day 5 after operation (P < 0.01). The epithelial mucosa in group III
      completely sloughed on day 7 after operation. CONCLUSIONS: Apoptosis plays an
      important role in small intestinal allograft rejection. Detection of apoptotic
      cells with TUNEL could be a valuable tool for the diagnosis of small intestinal
      allograft rejection.

PMID- 11829867
TI  - [The effects of n-3 fatty acid, fructose-1, 6-diphosphate and glutamine on
      mucosal cell proliferation and apoptosis of small bowel graft after
      transplantation in rats].
AB  - OBJECTIVE: To evaluate the effects of n-3  fatty acid (n-3 FA), fructose-1, 6
      diphosphate (FDP) and glutamine (GLN) on mucosal cell proliferation and apoptosis
      of small bowel graft. METHODS: 196 inbred strain Wistar rats underwent
      heterotopic small bowel transplantation (SBT) as donors and recipients
      respectively. n-3FA, FDP and GLN were given via gastrolavage as well as venous
      infusion within total parenteral nutrition (TPN) solution for 10 days before and
      after surgery. Flow cytometry and in situ cell death detection were used for
      analysing the changes of mucosal cell proliferation and apoptosis. RESULTS: Fewer
      proliferation and more apoptosis took place in mucosal cells of small bowel graft
      after transplantation. A higher mucosal cell proliferative index and lower
      apoptotic index were found in all small bowel graft after supplying with n-3FA,
      FDP and GLN. CONCLUSIONS: n-3FA, FDP and GLN specific nutritional support
      significantly promoted mucosal cell proliferation, and on the other hand
      inhibited mucosal cell from undergoing apoptosis with different degrees. The
      effects of regulation help improve the structure and absorption function of
      transplanted small bowel.

PMID- 11829868
TI  - [Precise positioning for reconstruction of anterior cruciate ligament].
AB  - OBJECTIVE: To supply the basement for precise positioning for anterior cruciate
      ligament (ACL) reconstruction in the knee and recommend a precise measurement
      method during the operation. METHODS: Bone tunnels along ACL attachments were
      made in 20 cadaveric knees. Steel wire was introduced through the tunnel and the
      length changes were measured during passive knee flexion. We developed an
      Isometer for getting continuous parameters. RESULTS: Anterosuperior (AS) fibers
      were lengthened during knee flexion from 30 to 120 degrees, combined with the
      increase of anterior restraints. Length changes of the posterosuperior and
      central (C, PS) fibers were minimal. The length of the anteroinferior and
      posteroinferior (AI and PI) fibers were shortened with the decrease of the
      anterior restraints. CONCLUSIONS: The central and posterosuperior (C, PS) parts
      of femoral attachment would be the ideal reconstruction point. In case of old
      injury of ACL with ambiquous landmark, the Isometer is suggested in identifying
      the reconstruction point.

PMID- 11829869
TI  - [Transfection of articular chondrocytes with PcNDA3-hBMP3 and its stable
      expression].
AB  - OBJECTIVE: To explore the possibility of stable expression of PcDNA3-hBMP3 in
      cultured articular chondrocytes of rabbit. METHODS: PcDNA3-hBMP3 was constructed
      using gene clone technique and recombined DNA technique. With the help of
      profectamine, the cultured articular chondrocytes were transfected with PcDNA3
      hBMP3, and the evidence of successfully stable transfection in these cells could
      be obtained by positive northern blot. RESULTS: The cultured articular
      chondrocytes of rabbits seemed to be polygonal, and its logarithmic growth phase
      was 2 - 4 days after cell inoculation. The two fragments cut from PcDNA3-hBMP3 by
      EcoR I and Xba I represented 5.4 kb and 1.4 kb by electrophoresis, which were
      confirmed to be the carrier and the fragment inserted originally, indicating that
      the construction of PcDNA3-hBMP3 was successful. The RNA extracted from cultured
      chondrocytes was screened for 4 weeks by G418 hibrided with the fragment cut from
      hBMP3 positively. CONCLUSIONS: With the help of profectamine, the cultured
      articular chondrocytes can be transfected by recombined gene of PcDNA3-hBMP3
      successfully, and their stable expression at 4 weeks after transfection is
      obtained.

PMID- 11829870
TI  - [Bone tissue engineering seeded with bone marrow stromal cells].
AB  - OBJECTIVE: To assess the ability of bone graft substitutes to support the growth
      of cells in vitro and new bone formation in vivo. METHODS: The methods of tissue
      engineering were employed, the bone marrow derived stromal cells were seeded onto
      blocks of hydroxypatite (HA), cultured for two weeks, and implanted
      intermuscularly into the rabbit back muscle, scanning electron microscopy and
      undecalcified bone tissue sections were used to evaluate the the growth of cells
      in vitro and new bone formation in vivo. RESULTS: The stromal cells were attached
      to and grew upon the surface of the periphery HA pores, especially in the pores
      adjacent to the bottom of culture flasks. No cell growth was found on the surface
      of the central pores. At four weeks after implantation, new bone formation was
      observed in most HA blocks, almost all of the new bones were lamellar bone and
      deposited directly on the surface of the HA pore. Active osteoblast and osteoid
      were found on the surface of the newly formed bone, invasion of bone marrow was
      observed in some newly formed bone. CONCLUSION: Bone marrow stromal cells are
      potentially the source of seeded cells for use in bone tissue engineering, and
      the HA may be considered as a suitable scaffold for these cells. The findings may
      be useful for detailed researches on seeded cells, scaffold and implanting
      fashion of bone tissue engineering.

PMID- 11829871
TI  - [Expression of BMP-2, TGF-beta, bFGF in guided bone regeneration].
AB  - OBJECTIVE: To study the mechanism of guided bone regeneration combined with
      osteoinduction by observation of expression of BMP-2, TGF-beta, bFGF. METHODS: 42
      adult, male, New Zealand rabbits were randomly divided into 6 groups, each group
      being 7 rabbits. 10mm standard bone defect model was produced bilaterally in the
      middle radial shaft of each rabbit. Randomly, one defect enveloped with silicon
      membrane was tested, and the other served as control, sacrificed at 3 days, 1, 2,
      3, 4, 5 weeks after surgery for histological observation, immunohistochemical
      staining of BMP-2, TGF-beta, bFGF and in situ hybridization of their cDNA probes.
      RESULTS: Histologically bone defects was sealed by silicon membrane, in which
      inflammation tissue and callus were formed from cells in bone ends. Similar
      expression of BMP-2, TGF-beta, bFGF between the test groups and control groups
      was noted. Inflammatory cells in the hematoma expressed bFGF and proliferating
      periosteal cells, endosteal cells, medullary mesenchymal cells expressed TGF-beta
      at 3 days postoperatively. Osteocytes in the bone ends and osteoblasts lining
      callus surface started to express BMP-2, TGF-beta at first week after surgery.
      Following the formation of inflammation tissue, in which giant cells,
      macrophages, mesenchymal cells expressed TGF-beta, bFGF respectively. Although
      the expression of three osteoinductors was the same between the test and control
      sides, their content was very different in both sides. The whole content in all
      test sides was much more than all control sides (P < 0.01), the content of test
      side was also much more than control side in each group. CONCLUSIONS: It is a key
      reason for successful guided bone regeneration that membrane tube formed a
      relatively independent bone regenerative situation to prevent around tissue from
      interruption, and to prevent osteoinductors from diffusion, so that enhanced
      osteoinductors induced bone regeneration to repair bone defects.

PMID- 11829872
TI  - [Construction of porous hydroxyapatite (HA) block loaded with cultured
      chondrocytes].
AB  - OBJECTIVE: To construct a kind of bone healing enhancing implant with cultured
      chondrocytes bound to hydroxyapatite (HA). METHODS: Chondrocytes were obtained
      from the costicartilage of rat and were cultured on the porous HA blocks, 3 mm x
      3 mm x 4 mm size, for three and seven days. Scanning electron micrograph was
      taken to show whether the cells grew outside and inside the pore of HA block. The
      cells cultured on tiny glass sheet for 2 days were used to prove where the cells
      come from by in situ hybridization technique with alpha1 (II) cDNA probe.
      RESULTS: Scanning electron micrographs showed that the pores of the HA surface
      and inside of the blocks are filled with cultured cells, especially the longer
      cultured block. The cells were chondrocytes confirmed by in situ hybridization.
      CONCLUSION: The porous HA can be used as cell cultured substrate and chondrocyte
      can adhere and proliferate inside the porous HA block.

PMID- 11829873
TI  - [Effect of wear particles on cell-to-cell communication of synoviocyte system in
      vitro and its significance in aseptic loosening of prosthesis].
AB  - OBJECTIVE: To study the biological reason of abnormal fiber proliferation at bone
      implant interface of aseptically loosened prosthesis by observing cell-to-cell
      communication of synoviocyte system in vitro under the stimulation of wear
      particles. METHODS: The synoviocyte system of normal human hip joint was
      established in vitro and the change of cell-to-cell communication was monitored
      by fluorescence redistribution after photobleaching technique (FRAP) and confocal
      laser scanning microscope (CLSM) after Ti alloy, CoCr alloy or UHMWPE particles
      suspension (1.5 mg/ml, W/V) was added into the system. RESULTS: Cell-to-cell
      communication of synoviocyte system significantly decreased under the stimulation
      of three kinds of particles (P < 0.01). he decreased degree was maximal in UHMWPE
      group and minimal in Ti alloy group (P < 0.01). The cell-to-cell communication
      level of fibroblast-like-cells (FCs) was significantly lower than that of
      macrophage-like-cells (MCs) (P < 0.05). CONCLUSIONS: Besides the effect of
      cytokines promoting fiber proliferation, the great amount of fibrous granuloma at
      bone-implant interface which has relations with aseptic loosening may be caused
      by the decrease of cell-to-cell communication of fibroblast under direct
      stimulation of wear particles.

PMID- 11829874
TI  - [The effects of platelet-derived growth factor on rat osteoblastic DNA contents].
AB  - OBJECTIVE: To study the effects of platelet-derived growth factor (PDGF) on the
      DNA content of the isolated osteoblast-like cells and the cellular period
      changes, and further study the effect of PDGF on bone fracture healing. METHODS:
      The cultured osteoblast-like cells in vitro were isolated from fetal rat calvaria
      and the effects of PDGF on cellular DNA contents were observed under flow
      cytometer. The changes of osteoblastic surface structure and ultrastructure were
      observed under electron microscope. RESULTS: PDGF could increase the DNA contents
      of cellular S period by promoting osteoblast from G0/G1 period into S period. The
      effects of PDGF on increasing cellular DNA contents were most significant at 24th
      culture hour (DNA content: 17.6% at the 24th hour, 9.0% at the 48th hour, 10.2%
      at the 72nd hour). PDGF could increase osteoblastic surface granules, reticular
      fibers and intracellular calcium salt crystals, and calcium granule mitochondria.
      CONCLUSIONS: PDGF could promote bone fracture healing by stimulating osteoblastic
      DNA synthesis and cell proliferation. The flow cytometer is a better instrument
      to analyze cell DNA content for a large number of cells.

PMID- 11829875
TI  - [Portal hypertensive vasculopathy of splenic artery].
AB  - OBJECTIVE: To study the pathological changes of splenic artery wall in portal
      hypertensive patients. METHODS: The pathological changes and iNOS activity of
      splenic artery wall were studied in 21 patients with liver cirrhosis and 15
      normal subjects, using light and electron microscope and immunohistochemistry.
      RESULTS: Compared with normal individuals, the splenic artery of cirrhotic
      patients showed that the intima was thickened, split and broken, and the smooth
      muscle layer of middle membrane was thicker and migrated to underintima space. In
      cirrhotic patients, regression, atrophy or hypertrophy and hyperplasia were seen
      in smooth muscle cells whose contractile phenotype changed to synthetic phenotype
      as well. iNOS activated obviously. Extracellular matrix increased in the wall,
      resulting in collagenic and fibrous changes. CONCLUSIONS: Hemodynamic alteration
      due to liver cirrhosis induced pathological changes of splenic artery, including
      the damage to contractile structure and increase of iNOS activity. It is one of
      the reasons of decrease of artery reaction to contractile vasoactive materials.

PMID- 11829876
TI  - [Recovery of gastrointestinal motility following laparoscopic versus open
      cholecystectomy].
AB  - OBJECTIVE: To investigate the recovery of gastrointestinal motility after
      laparoscopic cholecystectomy (LC) and open cholecystectomy (OC). METHODS: Motilin
      (MOT), gastrin (GAS), electrogastrogram (EGG), the peristaltic sound recovery
      timing (PSRT) and the anorectum exhaust timing (AET) were determined in 30
      patients having LC and 18 patients having OC. RESULTS: MOT, GAS, EGG frequency
      and EGG amplitude on the first, second and third day after operation in LC group
      were not significantly different in comparison with preoperative data (P > 0.05),
      but significant difference on the first and second postoperative day compared
      with preoperative data and data of the the LC group (P < 0.05). The PSRT and AET
      in the LC group were much shorter in comparison with the OC group (P < 0.05).
      CONCLUSIONS: The recovery of gastrointestinal motility after LC is earlier than
      OC, which justifies early feeding for patients after LC.

PMID- 11829877
TI  - [Apoptosis increased by bcl-2 antisense ODN in MCF-7 cell line].
AB  - OBJECTIVE: To study the effects of bcl-2 antisense oligonucleotides (ODN) on the
      expression of bcl-2 and apoptosis in MCF-7 cell line. METHODS: Artificially
      synthesized bcl-2 specific antisense OND was introduced into MCF-7 cells by gene
      pulser electroprotocol. Fluorescence microscope, electron microscope,
      immunocytochemical staining assay, and FCM were used to detect the effects on
      cell apoptosis, expressional level of bcl-2 protein and cell cycle after
      transfecting bcl-2 antisense ODN. RESULTS: The number of apoptotic cells was
      increased and expression of bcl-2 protein was declined (P < 0.05). FCM showed
      that the number of G(0)-G(1) phase cells was decreased and the number of G(2)-M,
      S phase cells were increased. CONCLUSIONS: The effective transient expression of
      bcl-2 antisense ODN can be obtained by gene pulser electroprotocol in MCF-7 cell,
      the function of bcl-2 gene was declined and the number of apoptotic cells was
      increased after transfecting bcl-2 antisense ODN. bcl-2 may be used as an useful
      target in tumor research.

PMID- 11829878
TI  - [Chemotherapeutic failure in micrometastasis in peripheral blood of patients with
      colorectal carcinomas].
AB  - OBJECTIVE: To study chemotherapeutic failure in the micrometastasis in peripheral
      blood of patients with colorectal carcinomas and its clinical significance.
      METHODS: We investigated the changes of micrometastasis in peripheral blood of
      patients with colorectal carcinomas before and after chemotherapy. RESULTS: The
      positive rate of CK2O mRNA in peripheral blood was 58.3%. Five more positive
      cases were detected 3 days after operation than before operation. After early
      short-term chemotherapy following operation, 22 cases turned to be negative. The
      maintaince of micrometastasis in peripheral blood after chemotherapy was
      significantly related to bcl-2 expression and p53 mutation in cancer tissues.
      CONCLUSIONS: The early short-term chemotherapy after operation plays a role in
      controlling the micrometastasis of colorectal carcinoma. The study of
      chemotherapeutic effect on micrometastasis in peripheral blood and its relation
      with the related genes may contribute to the selection of drugs and plans of
      adjuvant treatment.

PMID- 11829879
TI  - [Clinicopathologic study of 11 patients with Paget's disease of scrotum].
AB  - OBJECTIVE: To probe the relationship of clinicopathologic presentations and
      prognosis of Paget's disease primarily involving the scrotum. METHODS: 11 cases
      of scrotal Paget's disease were studied retrospectively from 1984 to 1997. PAS
      was stained and EMA, S-100, HMB45, CEA and CA15-3 were immunostained in all cases
      for the differential diagnosis from Bowen's disease and malignant melanoma.
      RESULTS: Six of 11 cases involved hair follicle and/or sweat glands, and 3 cases
      involved dermis (one had metastasis of left superficial and deep inguinal lymph
      nodes, and left internal iliac lymph nodes). Paget's cells were positive for PAS
      (11/11), EMA (11/11), CEA (6/11), CA15-3 (11/11), and negative for S-100, HMB45.
      Wide local excision of the lesions was performed in 10 of 11 patients both for
      primary disease and recurrent disease. 3 of the 10 patients underwent lymph nodes
      resection and metastasis was found in 1 case pathologically. One patient accepted
      chemotherapy and died, from respiratory insufficiency after one month. The other
      10 patients were followed up for 6 to 127 months and no patient died of Paget's
      disease. CONCLUSIONS: Involvement of hair follicles and sweat glands by Paget's
      cell does not influence the prognosis.However, invasion of dermis by Paget's
      cells may suggest possible metastasis.

PMID- 11829880
TI  - [The application of intraoperative cholangiography in laparoscopic
      cholecystectomy].
AB  - OBJECTIVE: To evaluate the role of intraoperative cholangiography in laparoscopic
      cholecystectomy (LC). METHODS: Intraoperative cholangiography was attempted in 1
      466 patients, and was successfully completed in 1382 patients. The success rate
      was 94.27%. RESULTS: Stones in the common bile duct in 92 patients, bile duct
      injury in 8 patients and abnormal bile duct in one patient were found.
      CONCLUSIONS: Intraoperative cholangiography is an accurate and safe procedure,
      can provide clear films of biliary tree, and has a high success rate. Its
      application can reduce the rate of bile duct injury and improve the quality of
      LC.

PMID- 11829881
TI  - [19 cases of Paget's disease].
AB  - OBJECTIVE: The clinical signs of Paget's disease are similar to those of chronic
      eczema. The two are often confused, especially extramammary Paget's disease. Only
      biopsy can help to differentiate them correctly. METHODS: 19 patients with
      Paget's disease were reviewed with regard to clinical analysis and treatment from
      1987 to 1997. RESULTS: Six patients had breast Paget's disease and 13 had
      extramammary one. The latter involved scrotum and penis in 11 patients, the groin
      in 1, and perianal and anal in 1. Follow up showed that 3 patients had
      recurrences in extramammary patients who had had positive surgical margin biopsy.
      One patient died of other disease. CONCLUSIONS: Surgery is the first choice of
      treatment for Paget's disease either of breast or of extramammary regions.
      Negative margins must be achieved to prevent local recurrence.

PMID- 11829882
TI  - [Surgical treatment of dissecting aneurysm of the interventricular septum].
AB  - OBJECTIVE: To report a kind of extremely rare disease, dissecting aneurysm of the
      interventricular septum. METHODS: Between May 1992 and January 1998, 4 patients
      underwent surgical treatment of dissecting aneurysm of the interventricular
      septum in Fuwai Hospital, Beijing. The cause of the disease was different in
      these four patients. Two patients may be attributable to the aneurysm of coronary
      sinus of valsava, 1 to the result of trauma, and the other to big perforation
      (diameter: 2 cm) in the bottom of the right coronary sinus of valsava, through
      which the blood rushed into the cavity of dissecting aneurysm of the
      interventricular septum. The aneurysm was resected or repaired in these patients.
      Three of them were subjected to aortic valve replacement and one received repair
      of the perforation of the right vaslava sinus. RESULTS: Two patients had
      successful reoperation and the other 2 suceeded in the first operation. All of
      them were uneventfully recovered. CONCLUSIONS: The development of dissecting
      aneurysm of the interventricular septum is rapid. Its prognosis is poor. Early
      diagnosis and operation are necessary. The pathogenic mechanism of dissecting
      aneurysm of the interventricular septum is unknown, but echocardiogram,
      electrocardiogram and nuclear magnetic resonance (NMR) are valuable for
      diagnosis. Surgical operation should involve the treatment of aortic valve
      disease. The wall of the aneurysm should be resected and the interventricular
      septum should be reconstructed. Good exposure can be obtained from the incision
      of the ascending aorta and right ventricular outflow tract. The A-V block should
      be treated simultaneously.

PMID- 11829883
TI  - [Treatment of complex crainocervical junction malformation by transoccipito
      cervical posterolateral approach].
AB  - OBJECTIVE: To report the treatment of six patients suffering from complex
      craniocervical junction (CCJ) malformation by transoccipitocervical
      posterolateral approach which is a new surgical method. METHODS:
      Transoccipitocervical posterolateral approach was confirmed feasible by anatomy
      of the body. Diagnosis was made sure CT-three dimensional image and MRI for every
      patient. All cases reaived odontoidectomy and suboccipital decompression and/or
      bone graft. RESULTS: All patients showed favorable outcome without deterioration
      or recurrence. Six patients were followed up for 15 - 10 months. All patients
      showed marked progressive improvement of neurological disturbances and three of
      them resumed work half a year after operation. CONCLUSION: Transoccipitocervical
      posterolateral approach is a new surgical procedure by which anterior and
      posterior decompression of foramen magnun aria and bone graft (posterior
      craniocervical stabilization) could be fulfilled during one operation.

PMID- 11829884
TI  - [Extracorporeal shock wave lithotripsy in situ for middle ureteral stones].
AB  - OBJECTIVE: To report the experience with in situ ESWL for patients with middle
      ureteral stones. METHODS: 52 patients suffering from stones with an average 11 mm
      (range 5 - 20 mm) in dimension were treated using modified Puigvert technique in
      prone position via the entry route of lateral abdomen. The patients received
      3,000 - 5,000 shocks per session at the power setting ranged from 2 to 7.
      RESULTS: The stone free rate at 3 months was achieved in 96% patients retreatment
      was performed in 30% patients. The therapeutic results were calculated as
      efficiency quotient being 74%. No severe complications occurred in all patients.
      CONCLUSIONS: In situ ESWL for middle ureteral stone is safe and effective and may
      serve as the first line therapy.

PMID- 11829885
TI  - [Long-term efficacy of transurethral electrovaporization of the prostate for
      symptomatic benign prostatic hyperplasia].
AB  - OBJECTIVE: To observe long-term efficacy of transurethral electrovaporization of
      the prostate for symptomatic benign prostatic hyperplasia. METHODS: Two types of
      electrode of transurethral electrovaporization of the prostate (TVP) were
      performed on 150 patients of symptomatic BPH (mean age 74.8 years). The patients
      were assessed at baseline for both efficacy and followup at 36 months. Efficacy
      parameters evaluated included operation time (minutes), I-PSS and quality of life
      score, digital rectal examination, transrectal ultrasound, urodynamics and
      postvoid residual urine. RESULTS: 36 months after operation, I-PSS was decreased
      from 24.8 to 5.4 and the quality of life score also was decreased from 4.9 to
      2.1. The mean peak uroflow was increased from 9.8 to 18.5 ml/s and postvoid
      residual urine was decreased from 108 ml to 22 ml (P < 0.05). The mean operation
      time was 44.7 min. Urodynamic results of 139 cases (92.7%) showed no bladder
      outlet obstruction, the remaining 11 cases showed severe bladder outlet
      obstruction to mild obstruction after 36 months. Hematuria was the only
      complication of our procedure. CONCLUSIONS: Significant clinical improvement is
      maintained with minimal morbidity. The long-term efficacy and safety of TVP is
      satisfactory. TVP is a potential useful procedure for transurethral resection of
      the prostate.

PMID- 11829886
TI  - [Retroviral-mediated transfer of a hygromycin phosphotransferase-thymidine kinase
      fusion gene into human bladder carcinoma cell].
AB  - OBJECTIVE: To evaluate the therapeutic efficacy of retroviral-mediated hygromycin
      phosphotransferase-thymidine kinase fusion gene (HyTK)/GCV on human bladder
      carcinoma cell. METHODS: A retroviral expression vector pL (HyTK) SN was
      constructed. By using FuGENE 6-mediated transfection and "ping-pong effect"
      technique, high-titer of retroviral supernatant was obtained and HyTK gene was
      transferred into EJ cells. A retroviral vector encoding, enhanced green
      fluorescent protein, EGFP was used to rapidly detect the transduction efficiency.
      Antitumor effects were observed after GCV treatment. RESULTS: In vitro
      experiments demonstrated the EJ cells transferred by HyTK gene were killed in the
      GCV treatment. Non-transduced parental cells were not sensitive to GCV, but they
      were dead by the bystander killing of neighboring cells when mixed with EJ/HyTK
      cells at various ratios. In addition, this not only affect wild-type EJ cells but
      also cells from different bladder carcinoma cell lines. CONCLUSIONS: Retroviral
      mediated HyTK/GCV systems were a promising suicide gene therapy for bladder
      carcinoma. EGFP may act as a convenient and rapid reporter to monitor retroviral
      mediated gene transfer and expression in bladder carcinoma cells.

PMID- 11829887
TI  - [Multiple inhibitory mechanisms of wild-type p16 gene transfer into human bladder
      cells by retroviral vector].
AB  - OBJECTIVE: To investigate the inhibitory mechanisms of wild-type p16 gene
      transfer into human bladder cancer cells with or without endogenous p16 gene
      expression. METHODS: p16 recombinant retrovirus vector was constructed and
      transfected in human bladder cancer cell EJ and 253J. Northern blot analysis and
      immunocytochemistry were used to detect the expression of exogenous p16 gene.
      Flow cytometry analysis was used to detect tumor cell cycle. Electronic
      microscope and in situ labelling apoptotic DNA fragment detection (TUNEL) was
      used to detect tumor cell apoptosis after gene transfection. Tumorigenicity was
      observed in nude mice. RESULTS: The growth rate of the transfected EJ cells was
      significantly retarded, the majority of transfected EJ cells were arrested on
      G(0) + G(1) phases of cell cycle, tumorigenicity of the transfected cells was
      reduced on nude mice. H-ras gene expression in transfected EJ cells reduced as
      compared with non-transfection. Apoptotic cells were observed in transgenic 253J
      cells. CONCLUSIONS: Malignant proliferation of bladder cancer cells can be
      inhibited by exogenous p16 gene transfection via different molecular pathway.

PMID- 11829888
TI  - [E-CD expression and its clinical significance in human bladder carcinoma].
AB  - OBJECTIVE: To invest the expression of the E-CD protein and its clinical
      significance in human recurrent bladder transitional cell carcinoma. METHODS:
      Immunohistological chemistry method was employed to assess the expression of E-CD
      in 54 cases of bladder transitional cell carcinoma. RESULTS: Decreased E-CD
      expression correlated with both increased grade and stage (chi(2) = 6.65, P <
      0.05; chi(2) = 7.15, P < 0.01). More importantly, abnormal expression of E-CD
      correlated with the high recurrence in short time and the poor survival (chi(2) =
      4.88, P < 0.05; Log-rank test: chi(2) = 4.6, P < 0.05). CONCLUSIONS: The
      expression of E-CD is an useful parameter of malignancy of carcinoma. The
      detection of E-CD expression might be significant in determining the malignancy,
      recurrence and prognosis of bladder transitional cell carcinoma.

PMID- 11829889
TI  - [Transcatheter arterial embolization of renal carcinoma with absolute ethanol].
AB  - OBJECTIVE: To study transcatheter arterial embolization (TAE) of renal carcinoma
      using absolute ethanol so as to reduce bleeding for a higher resection rate, as a
      palliative treatment for advanced renal carcinoma. METHODS: Using Seldinger
      method, we treated 25 cases of renal carcinoma with transcatheter arterial
      embolization. RESULTS: The average bleeding of 25 cases during nephrectomy was
      210ml after TAE. There was no mortality and serious complication. But there was
      pain and fever in most cases. CONCLUSIONS: TAE with absolute ethanol is an
      effective, safe and easy procedure. It could be used as an adjuvant therapy for
      renal carcinoma.

PMID- 11829890
TI  - [Prevention of postoperative recurrence of bladder cancer: a clinical study].
AB  - OBJECTIVE: To lower postoperative recurrence rate of bladder cancer, the
      prophylactic effects of five kinds of method on bladder cancer were evaluated.
      METHODS: Between 1982 and 1997, 313 patients after TURBT or partial cystectomy
      were followed up for 2 to 15 years (average 7.6 years). These patients were
      divided into six groups: BCG, mitomycin C (MMC), thiotepa, Chinese herb medicine
      Zhuling (Grifola umbellata pilat), afterloading brachytherapy and control group.
      The prophylactic effects of them on postoperative recurrence of bladder cancer
      was evaluated. RESULTS: During the follow-up, the recurrence rates were 35.1% in
      BCG group, 34.9% in Zhuling group, 41.7% in MMC group, 52.6% in thiotepa group,
      64.7% in control group, respectively. 25 high-risk patients with invading or
      multiple bladder cancer were treated by afterloading brachytherapy. They were
      followed up from 12 to 42 months, with a recurrence rate being 24.0%.
      CONCLUSIONS: The prophylactic effect of Zhuling and BCG on bladder cancer
      recurrence was better than MMC. The vale of thiotepa was not significant. The
      afterloading brachytherapy was of great vale to invading or recurrent, multiple
      bladder cancer.

PMID- 11829891
TI  - [Internal drainage combined with intraoperative radiotherapy and chemotherapy for
      pancreatic head carcinoma].
AB  - OBJECTIVE: To improve the palliative effect on intermediate or advanced
      pancreatic head carcinoma. METHODS: 26 patients with intermediate or advanced
      pancreatic head carcinoma underwent cholecystojejunostomy combined with
      intraoperative radiotherapy with an electron beam on carcinoma from May 1996 to
      May 1998. The catheter of multifunctional implantable drug delivery system was
      inserted via gastroduodenal artery for postoperative perfusion chemotherapy.
      RESULTS: Follow-up for 3 - 27 months showed that all carcinomas shrunk with pain
      released in different degrees after a course of treatment. The 6-month, 12-month
      and 24-month survival rates were 100%, 93.9% and 20% respectively. Five patients
      survived on the average for 17.8 months. CONCLUSIONS: This protocol is effective
      to prolong the life of the patients with intermediate or advanced pancreatic head
      carcinoma.

PMID- 11829892
TI  - [Comparison of different alimentary reconstructions after total gastrectomy for
      cancer].
AB  - OBJECTIVE: To study the optimum reconstruction after total gastrectomy for
      malignant disease, especially the necessity of gastric substitute and duodenal
      passage. METHODS: Among 75 patients having total gastrectomy, five kinds of
      reconstruction were used: Braun, modified Braun (mBraun) I, II, III, and
      antigrade jejunal interposition (AJI). Postoperative complaints, body weight,
      food intake, serum nutritional parameters, complete blood count, half-emptying
      time of the gastric substitute, PNI, Visick index were evaluated. RESULTS: As
      compared with Braun group, the mBraun I and II groups showed less reflux
      esophagitis, higher nutritional parameters and PNI, while the operation time was
      similar. As compared with mBraun I and II groups, mBraun III and AJI groups
      showed better body weight, higher nutritional parameters, and PNI. CONCLUSIONS:
      It is essential to construct a gastric substitute and maintain the alimentary
      tract flowing through the duodenum after total gastrectomy for cancer, and the
      AJI may be a better choice in the operation of gastrectomy.

PMID- 11829893
TI  - [Operative treatment of acetabular fractures].
AB  - OBJECTIVE: To improve the level of the management of complicated acetabular
      fracture. METHODS: 56 acetabular fractures were treated operatively from March
      1993 to May 1998. According to Letournel-Judet classification, 7 cases were
      posterior wall fracture, 6 posterior column fracture, 4 anterior column fracture,
      6 transverse fracture, 6 T-shaped fracture, 10 posterior column combined
      posterior wall fracture, 6 transverse combined posterior wall fracture, 2
      anterior combined posterior hemi-transverse fracture and 6 both column fracture.
      Kocher-Langebeck approach, illioinguinal approach, illiofemoral approach,
      extended illiofemoral approach and anterior combined posterior approach were
      adopted for different fractures with reconstruction plates and screws. RESULTS:
      49 of 56 cases were followed up on an average of 26.4 months. According to
      Matta's evaluation, 19 cases (39%) showed excellent results, 24 (49%) good, 4
      (8%) fair, and 2 (4%) poor. Avascular necrosis of the femoral head was found in 4
      cases (8%) and heterotopic ossification in 15 cases (30.6%). No death and
      infection were found in this series. CONCLUSIONS: According to our experience,
      accurate analysis of fractures preoperatively, reasonable surgical approaches and
      timing of surgery are essential to good treatment of acetabular fractures.

PMID- 11829894
TI  - [A clinical analysis of L-dopa induced dyskinesia treated by posteroventral
      pallidotomy for Parkinson's disease].
AB  - OBJECTIVE: To evaluate the outcome of microelectrode-guided posteroventral
      pallidotomy (PVP) for L-dopa induced dyskinesia in patients with Parkinson's
      disease. METHODS: Thirty-six patients with dyskinesia were evaluated with unified
      Parkinson's disease rating scale (UPDRS) before and after operation. Duration and
      disability of dyskinesia were analyzed respectively. RESULTS: The total surgical
      improvement for dyskinesia was 76.2%. Duration improvement was 88.8% and
      disability 79.7%. Significant change (P < 0.05) happened postoperatively.
      Seventeen patients were followed up for 3 months. The result showed a stable
      improvement for dyskinesia. CONCLUSIONS: L-dopa induced dyskinesia may disappear
      or be improved after PVP. Surgical treatment promises a maximum L-dopa therapy
      without any severe pharmaceutical complications. Synergic treatment of drug and
      surgery are a new strategy for Parkinson's disease.

PMID- 11829895
TI  - [Microelectrode-guided posteroventral medial pallidotomy for Parkinson's
      disease].
AB  - OBJECTIVE: To introduce the methods and effects of microelectrode-guided
      posteroventral pallidotomy (PVP) for Parkinson's disease. METHODS: 109 patients
      underwent PVP by microelectrode electrophysiological recording for intraoperative
      target localization. 45 patients underwent unilateral PVP, 21 patients
      simultaneous bilateral PVP, 43 patients combined thalamotomy and PVP. Modified
      Webster Scale was used for objective assessments before and after operation.
      Postoperative CT scan or MRI was performed to localise lesions. RESULTS:
      Microelectrode recording usually led to a final pallidotomy lesion position that
      deviated from the CT stereotactically defined target point. The change rate of
      targets was 84.7%. PVP significantly and immediately improved all Parkinsonian
      motor signs and reduced drug-induced motor fluctuations and dyskinesia. The mean
      Webster Scale was improved by (72.7 +/- 11.3)% in the "on"" state, and (89.3 +/-
      8.1)% in the "off" state. No patient showed permanent complications. CONCLUSIONS:
      Microelectrode-guided PVP was proved to be safe and effective. Bilateral PVP and
      combined PVP can significantly and immediately abolish all Parkinsonian motor
      signs. Physiological methods of microelectrode recording can significantly
      improve the safety and efficacy of PVP, and decrease the rate of complication.

PMID- 11829896
TI  - [Operative results of tethered cord syndrome].
AB  - OBJECTIVE: To evaluate the treatment results of 22 cases of spinal tethered cord
      syndrome (TCS) using microneurosurgical technique. METHODS: Form 1994 to 1997, 22
      cases of TCS verified by MRI were treated. All patients'tips of conus were below
      L(2) vertebra shown by MRI. In this group, 4 cases had lipid disease in the
      sacral canal, 5 piloidal sinus, and 13 thick filum. The patients were operated on
      using linear incision. The incision included the terminal conus and the whole
      filum. Under the microscope, the adhesions of the caudal equine were separated
      and the filum was found out. The caudal equine was well combed. Lipoma and
      piloidal sinus were removed totally or partially. Loosening the spinal conus and
      repairing the dural matter prevented re-adhesion and re-tether. RESULTS: Follow
      up (0.5 - 3 years) showed that all of the patients were recovered in different
      levels. CONCLUSIONS: TCS should be found as early as possible and treated under
      the microsurgical technique.

PMID- 11829897
TI  - [MR urography in the diagnosis of upper urinary tract obstruction].
AB  - OBJECTIVE: To evaluate the role of magnetic resonance urography (MRU) in the
      diagnosis of upper urinary tract obstruction. METHODS: MRU was performed for 35
      patients suspicious of upper urinary tract obstruction. RESULTS: MRU provided
      high resolution images of the urinary tract. The site of upper urinary tract
      obstruction and hydronephrosis could be clearly shown. CONCLUSIONS: MRU, a
      nontraumatic technique, needs no iodinated contrast medium. It might be widely
      adopted in the diagnosis of upper urinary diseases.

PMID- 11829898
TI  - [Changes of interleukin-2 and soluble interleukin-2 receptor serum level and
      multiple organ dysfunction syndrome in severely traumatic patients].
AB  - OBJECTIVE: To evaluate the role in the changes of interleukin-2 (IL-2) and
      soluble interleukin-2R (sIL-2R) serum level in the mechanism of post-traumatic
      multiple organ dysfunction syndrome (MODS). METHODS: 59 severe traumatic patients
      were divided into MODS group (n = 24) and non-MODS group (n = 35) according to
      the occurrence of MODS after trauma. The changes in IL-2 and sIL-2R serum level
      were observed by enzyme linked immunoabsorbed assay (ELISA). Sera from 30 healthy
      individuals were used as normal controls. RESULTS: The serum level of sIL-2R was
      increased and that of IL-2 decreased in 59 traumatic patients. These changes were
      more marked in the MODS group than in non-MODS group (p < 0.05). CONCLUSIONS: The
      changes in IL-2 and sIL-2R serum level after trauma might participate in the
      mechanism of post-traumatic MODS.

PMID- 11829899
TI  - [The expression of MTS1 gene product in transitional mucosa adjacent to rectal
      carcinomas and its clinical significance].
AB  - OBJECTIVE: To study the property of transitional mucosa (TM) adjacent to rectal
      carcinoma and the clinical significance of MTS1 gene deficit. METHODS: We used
      the immunohistochemical methods to observe the range of TM adjacent to rectal
      carcinoma, and the immunohistochemical method to observe the expression of MTS1
      gene product on TM, using normal mucosa and carcinoma tissue as control. RESULTS:
      The positive expression level of MTS1 gene product was the highest in the normal
      rectal mucosa, gradually defective in TM and carcinoma tissue (P < 0.05). The
      range of TM with MTS1 negative cases was prominently larger than that with MTS1
      positive cases (P < 0.05). CONCLUSIONS: The inactivation of MTS1 gene is relative
      to the occurrence of rectal carcinoma, suggesting that the TM adjacent to rectal
      carcinoma possess as certain potential malignancy. TM is related to MTS1 gene
      expression deficit of rectal carcinoma, showing that MTS1 gene expression deficit
      or mutation may be a factor inducing transitional change adjacent to carcinoma.

PMID- 11829900
TI  - [The effect of 1, 25 (OH)(2)D(3)on growth and apoptosis in breast cancer cell
      line MCF-7].
AB  - OBJECTIVE: To study the effect of 1, 25-dihydroxyvitamin D(3) [1, 25 (OH)(2)D(3)]
      on growth and apoptosis in breast cancer cell line MCF-7. METHODS: We compared
      cell numbers by using MTT method, analyzed cell cycle and apoptosis percentage by
      flow cytometric, observed cellular structure and ultrastructure, determined
      quantitatively apoptosis cells by terminal deoxynucleotidyl transferase-mediated
      dUTP nick end labeling (TUNEL), and detected expression of bcl-2 protein by
      Western Blot. RESULTS: Incubation with 1, 25 (OH)(2)D(3) 10(-7) mol/L, MCF-7
      cells exhibited significant growth inhibition. Flow cytometric analysis indicated
      cell's G(0)/G(1) arrest along with increasing apoptotic peak and percentage. The
      action of cytotoxic drug Adr was strengthened. Western Blot showed that 1, 25
      (OH)(2)D(3) could down-regulate bcl-2 protein expression. CONCLUSIONS: 1, 25
      (OH)(2)D(3) could be a new hormone for the treatment of breast cancer.

PMID- 11829901
TI  - [Study on therapeutic effect of carnitine on hepatic steatosis caused by total
      parenteral nutrition in rats].
AB  - OBJECTIVE: To study the hepatic steatosis-minimizing effects of carnitine
      supplemented total parenteral nutrition (TPN). METHODS: Eighteen normal Wistar
      rats and nineteen cirrhotic Wistar rats were randomly divided into three groups,
      respectively: group A (12), chow and libitum; group B (13), TPN for one week
      group C (12), TPN with carnitine. Liver functions were tested at the seventh day,
      and also, the liver was resected for histological studies and lipid content
      determination. RESULTS: Hepatic lipid content was significantly elevated and
      hepatic steatosis was noted in group B. Hepatic lipid content and hepatic lipid
      deposit were significantly lowered when carnitine was added to the TPN solution.
      CONCLUSIONS: Carnitine can minimize hepatic steatosis caused by TPN.

PMID- 11829902
TI  - [Primary shortening followed by bone lengthening in situ for the treatment of
      gunshot bone defect].
AB  - OBJECTIVE: To study the treatment of gunshot bone defect and the biological basis
      of primary shortening followed by callus distraction in situ. METHODS: The canine
      with gunshot bone defect were treated by two methods, primary shortening followed
      by callus distraction or delayed bone graft. The local blood flow and
      pathomorphological change were observed and compared with each other. RESULTS: In
      the experiment, the bone lengthening was stopped at the 56th day with (2.82 +/-e
      0.94) cm (19.3%) gain in the group of bone lengthening, and the time of bone
      healing was much shorter in the group of bone lengthening than in the group of
      delayed graft. There was no significant difference between the groups in the time
      of soft tissue healing and local blood flow. CONCLUSIONS: The technique of
      primary bone lengthening is simple and has no side effect on tissue healing and
      local blood flow.

PMID- 11829903
TI  - [Intestinal blood perfusion improved by early enteral feeding in burned rat].
AB  - OBJECTIVE: To explore the mechanism of intestinal blood perfusion improved by
      early enteral feeding after burn injury. METHODS: Wistar rats were inflicted with
      30% total body surface area full thickness flame burn and randomly divided into
      three groups: burned control (B), burned and early feeding (EF), and normal
      control (C). The content of endothelin (ET), nitric oxide (NO), vasoactive
      intestinal peptide (VIP), and intestine mucosal blood flow (IMBF) were determined
      at postburn 0, 3, 6, 12, 24, 48 hours. RESULTS: The content of ET, NO, VIP in
      small intestine as well as the ratio of ET/NO, ET/VIP were increased
      significantly and the IMBF was decreased markedly postburn. In EF group, ET,
      ET/NO and ET/VIP were significantly lower (P < 0.05, P < 0.01), and NO, VIP as
      well as IMBF were higher than those in B group (P < 0.05, P < 0.01). There were
      negative correlation between ET/NO, ET/VIP and IMBF (r(1) = -0.95, P < 0.01; r(2)
      = -0.87, P < 0.01). CONCLUSIONS: The mechanism of intestinal blood perfusion
      improved by early enteral feeding may be correlated with increased NO, VIP and
      decreased ET induced by foods stimulating intestinal nerve.

PMID- 11829904
TI  - [Radiculopathy after cervical laminectomy].
AB  - OBJECTIVE: To investigate radiculopathy after multilevel laminectomy in patients
      with cervical compression myelopathy and underlying mechanism. METHODS: We
      retrospectively reviewed 287 consecutive patients with cervical compression
      myelopathy treated by multilevel cervical laminectomy and identified 37 patients
      (12.9%) with postoperative radiculopathy. There were 27 men and 10 women, with an
      average age of 56 years at time of surgery. The diagnosis was either cervical
      spondylosis (25 patients) or ossification of the posterior longitudinal ligament
      (12 patients). RESULTS: Radiculopathy was observed from 4 hours to 6 days after
      surgery. The most frequent patterns of paralysis were C(5) and C(6) root
      involvements of the motor-dominant type. All patients showed complete recovery in
      2 weeks to 3 years (average, 5.4 months). Follow up results showed that the
      recovery rate was negatively related to the duration of complete recovery of
      postoperative radiculopathy (r = -0.832, P < 0.01) and the patients with
      spondylotic myelopathy had a significantly better clinical recovery rate than
      those with ossification of the posterior longitudinal ligament (t = 2.960, P <
      0.01). CONCLUSIONS: Postoperative radiculopathy is complicated with posterior
      cervical decompression and associated with tethering effect upon the nerve root.
      More logical procedures for prevention of postoperative radiculopathy are
      decompression through an anterior decompressive procedure in conjunction with a
      spinal fusion, which may achieve stabilization and directly remove all of the
      anterior spinal cord compression at multiple levels.

PMID- 11829905
TI  - [Cervical spinal cord injury treated by expanded hemilaminectomy].
AB  - OBJECTIVE: To treat cervical spinal cord injury (SCI) accompanied with narrowing
      spinal canal by expanded hemilaminectomy. METHODS: From 1995 January to 1998
      April 51 patients of cervical SCI were treated by expanded hemilaminectomy.
      Spinal injury classified in to 3 types: no fracture-dislocation (39 patients)
      fracture dislocation at the lower cervical spine (11), and burst fracture (1).
      The types of SCI included central cord injury (18 patients) incomplete cord
      injury (19), and complete cord injury (14). MR imaging in 23 patients showed
      degenerative changes with normal intensity of the cord in 14 patients, multiple
      level hyperintensity in 3, cystic changes in 3, myelomalasia in 3, and cord
      brocken in 1. Expanded hemilaminectomy was performed in 24 hours in 3 patients,
      in 48 hours in 9, in one week in 2, after one week in 35, and after one year in
      2. The left or right laminae were removed from C(7) to C(3) in 42 patients, C(3) 
      T(1) in 3, C(2) - C(7) in 2, C(3) - C(6) in 3 and C(4) - C(7) in 3.
      Hemilaminectomy was expanded lateral to the inner of apophyseal joint and medial
      to the inner lamina beneath the spinal process. RESULTS: Follow-up lasted for 1
      year and 7 months. Six patients with complete cord injury had of the no recovery
      lower extremity but recovery of the brachialis and extensor radial longus. 12
      patients of central cord injury had full recovery except intrinsic muscles of the
      hand (5). They operated were on 2 weeks after injury. 17 patients of incomplete
      cord injury recovered to Frankel IV. CONCLUSIONS: Expanded hemilaminectomy is
      indicated for patients of cervical SCI with narrowing spinal canal or without
      fracture dislocation. Best results can be obtained in patients of central cord
      injury, and incomplete cord injury. Even in complete cord injury, 1 - 2 forearm
      muscle may recover (24.8%), securing a pinch grip reconstruction.

PMID- 11829906
TI  - [The relation between cord compression rate and the outcome of surgical
      treatment].
AB  - OBJECTIVE: To study the relation of compressive spinal cord changes in morphology
      with postoperative results. METHODS: 114 cases of operative patients were divided
      in to three groups: ossification of posterior longitudinal ligament (OPLL),
      cervical spondylotic myelopathy (CSM), and cervical intervertebral disc
      herination. The spinal cord plane and to the compressive ratio in the most
      heavily pressed position were measured according to the JOA record. RESULTS: The
      compressive ratio and the plane were not corelated with clinical history. The
      spinal cord plane was positively corelated with the recovery rate. CONCLUSIONS:
      The preoperative spinal cord plane in OPLL and CSM is mostly corelated with the
      recovery rate.

PMID- 11829907
TI  - [The relationship between cartilage end-plate calcification and disc
      degeneration: an experimental study].
AB  - OBJECTIVE: To study the relationship between cartilage end-plate calcification
      and intervertebral disc degeneration. METHODS: An experimental model of cervical
      disc degeneration in rabbits was established by resection of cervical
      supraspinous and interspinous ligaments and detachment of the posterior
      paravertebral muscles from cervical vertebrae. Mechanical instability in the
      cervical spine elicited by this surgical intervention accelerated the process of
      intervertebral disc degeneration. The degrees of intervertebral disc degeneration
      were graded morphologically. The thickness of the calcified layer and the
      uncalcified layer of the cartilage end-plate was measured in each degenerated
      cervical disc. RESULTS: A positive correlation existed between the thickness of
      the calcified layer of the cartilage end-plate and the degree of the cervical
      disc degeneration (r = 0.92). CONCLUSION: The calcification of the cartilage end
      plate could initiate and promote intervertebral disc degeneration.

PMID- 11829908
TI  - [Motor-evoked potential in investigating neurologic function during spinal cord
      ischemia and reperfusion injury].
AB  - OBJECTIVE: To investigate the method monitoring the neurologic function of spinal
      cord ischemia and reperfusion injury. METHODS: Motor-evoked potentials (MEP)were
      monitored at different time points during ischemia and reperfusion of the lumbar
      spinal cord of the rat. RESULTS: MEP latency increased 15 minutes after ischemia
      (P < 0.01) and MEP amplitude decreased 25 minutes after ischemia (P < 0.01). MEP
      disappeared 40 minutes after ischemia and reappeared 5 minutes after reperfusion,
      but the latency was still longer and the amplitude was lower than the normal
      value (P < 0.01). The amplitude returned to normal 2 hours after reperfusion (P >
      0.05) in contrast to the latency. 24 hours after reperfusion, the amplitude
      decreased again, and motor function of rat hind limbs was more decreased than
      that at early time of reperfusion (P < 0.05). CONCLUSION: MEP is a sensitive
      index for spinal cord ischemia and reperfusion injury.

PMID- 11829909
TI  - [Analysis and prevention of dislocation after total hip replacement].
AB  - OBJECTIVE: To analyse and prevent postoperative dislocation after total hip
      replacement (THR). METHODS: Of 850 cases operated on by THR 15 (1.7%) had
      postoperative dislocation. Eleven were revision cases while the other 4 were
      operated on their primary procedures. RESULTS: Postoperative dislocation after
      THR were found in 15 cases. Eleven cases had posterior dislocation by
      posterolateral approach after revision of THR. Anterior dislocation occurred in 2
      cases who received lateral approach. Another two cases of dislocation were
      related to the design of prosthesis. Separation of polyethylene liner and metal
      shell in acetabular prosthesis was noted in the two cases. All the cases but 1
      were reduced operatively. The cases with malpositioned prosthesis were revised
      operatively. Augmentation procedure was carried out to increase the strength of
      abductor. In one case, relocation of the great trochantor increased the strength
      of abductor. No redislocation was observed during follow-up. CONCLUSIONS:
      Postoperative dislocation after THR are due to malpositioning of prosthesis,
      unbalanced bilateral soft tissues, especially the loosening of abductor.
      Evaluating carefully the development of the pelvis and the deviation of normal
      bone markers is important in addition to accurate insertion and installment of
      the prosthesis intraoperatively. Complete clearance of osteophytes and bone
      cements around the acetabulumis reqaired apart from the repairment of adjacent
      soft tissues. Double check of hip stability should be carried out before the
      closure of incision.

PMID- 11829910
TI  - [Cytological diagnosis of Hashimoto's hyperthyroidism].
AB  - OBJECTIVE: To assess the value of thyroid fine needle biopsy (FNB) in Hashimoto's
      hyperthyroidism. METHODS: FNB for was performed 58 (5 males and 53 females, aged
      from 13 to 66 years) of 1 031 patients who was performed clinically dignosised as
      having hyperthyroidism according to clinic symptoms, the results of physical and,
      laboratory examination, especially the increased the serum circle antibody and
      lowered sTSH during March 1995 to February 1998. Their smears were classified
      into 4 types according to the degree of degeneration of adenoidal cell and
      lymphocyte invasion. RESULTS: Hyperthyroidism was observed in 5 cases, I type in
      9, II type in 9, III type in 4, and IV type in 31 (53%). CONCLUSIONS: FNB is
      helpful in diagnosis of hyperthyroidism.

PMID- 11829911
TI  - [Surgical treatment of truncus arteriosus in children].
AB  - OBJECTIVE: To summarize the surgical results of truncus arteriosus in children.
      METHODS: Five patients with persistent truncus arteriosus underwent complete
      repair of truncus arteriosus. Type I was found in 2 patients, type II in 2 and
      type IV in 1 according to Collett and Edwards. Their ages ranged from 3 to 12
      years (mean 6.3 years). The time of pulmonary circulation and evacuation of the
      pulmonary artery was not significantly prolonged. Complete repair was via a
      median sternotomy utilizing hypothemia with cardiopulmonary bypass, entailing
      separation of the pulmonary arteries from the truncus, repair of the resultant
      defect in the aorta, ventricular septal defect (VSD) closure with a patch in
      which the interrupted pledget-supported suture was placed in the truncal valve
      annulus of the superior border of VSD, and restoration of right ventricular
      outflow tract (RVOT) continuity utilizing extra cardiac conduits, of which
      autologous pericardial valved dacron conduit was used in 4 patients and homograft
      conduit in 1. RESULTS: Postoperative mean pulmonary pressure decreased
      significantly in all patients (P < 0.01) and the pressure gradient across conduit
      was 7 - 35 mm Hg. Two patients died immediately after the operation, which was
      not associated with pulmonary vascular lesion. Among 3 survivors, I had low
      cardiac output and respiratory dysfunction after operation and the others
      recuperated uneventfully. Survivors were followed up for a period of 114, 96 and
      34 months respectively, and were all in NYHA functional class I. One died of
      occlusion of conduit 8 years after operation. CONCLUSIONS: Children with truncus
      arteriosus are still indicated for complete correction. Autologous pericardial
      valved dacron conduit has excellent long-term outcomes. Correcting truncal valve
      insufficiency, repairing VSD, avoiding large pressure gradient across conduit and
      shortening CPB time are keys to improve the survival rate of patients and achieve
      excellent long-term outcome.

PMID- 11829912
TI  - [Limited pleuro-pneumonectomy for bronchogenic carcinoma associated with
      cancerous pleural effusion].
AB  - OBJECTIVE: To evaluate the effects of limited pleuro-pneumonectomy for
      bronchogenic carcinoma associated with cancerous pleural effusion. METHODS: From
      January. 1994 to December 1997 we performed limited pulmonary lobectomy wedge
      resection of lung, resection of the metastases of the parietal pleura, visceral
      pleura, diaphragmatic pleura and pericardiac pleura, and electro incision of the
      micormetastases of the above position as well as cleaning the mediastinal lymph
      nodes in 14 cases. RESULTS: The 14 cases were followed-up to December 1998. Eight
      patients of them died, the other 6 patients survived with a survival period of 7 
      30 months (median survival period 16.5 months). No pleural effusions recurrence
      was seen. The longest survival period was 30 months. There were no operative
      mortality and no severe postoperative complication. Chest distress, dyspnea and
      pain of chest or abdomen were relieved. CONCLUSIONS: This simple method has such
      advantages as, less traumatic, rapid rehabilitation and effective control of
      pleural effusion. The postoperative survival period is longer than that of
      palliative operation and medical therapy. The pain caused by parietal pleural
      metastasis can be relieved.

PMID- 11829913
TI  - [Effect of testosterone on spermatogenesis: dynamics of testosterone secretion in
      adult rat testis].
AB  - OBJECTIVE: To study the effect of testosterone on spermatogenesis. METHODS:
      Testosterone concentrations were measured in testicular interstitial fluid (IF),
      and serum sample from the testicular artery, testicular veins on the surface of
      the testis, and the peripheral venous, inferior vena cave and proximal spermatic
      veins in adult SD rats. The left and bilateral veins at the proximal end of the
      spermatic cord were ligated respectively. Testosterone concentrations and weight
      of the testis were measured, and the changes of the testicular morphology were
      studied 3 days and 21 days after ligation respectively. RESULTS: The testosterone
      concentrations were highest in IF. The serum testosterone concentrations were
      highest in the testicular veins on the surface of the testis. The serum
      testosterone concentrations in the proximal spermatic veins, the testicular
      artery, the peripheral venous and inferior vena cave were (42.503 +/- 12.749),
      (42.503 +/- 12.749), (5.598 +/- 3.649), (2.533 +/- 1.719) and (2.418 +/- 1.495)
      mg/L respectively. Three days after the proximal spermatic veins were ligated
      bilaterally, the weights of the testis and the serum testosterone concentrations
      declined markedly. The epithelium of the seminiferous tubules degenerated
      slightly and part of the structure was indistinct. Three days after the left
      proximal spermatic veins were ligated, the weights of the left testis, the
      testosterone concentrations in the left IF and in the serum of the left
      testicular artery declined distinctly except the serum testosterone concentration
      of the peripheral venous, inferior vena cave and those of the right testis. The
      epithelium of the seminiferous tubules in the left testis degenerated slightly
      and part of the structure was indistinct. It was restored 21 days after ligation.
      CONCLUSIONS: A "small circulation" (testis-the testicular veins-the spermatic
      veins-the spermatic artery-the testicular artery-testis) may exist. The results
      indicate that after ligation of the proximal spermatic veins, the reduction of
      the testosterone concentrations and changes of testicular morphology is temporary
      and may be recovered.

PMID- 11829914
TI  - [The effect of sandostatin and 5-fluorouracil on apoptosis in breast cancer].
AB  - OBJECTIVE: To investigate the effect of 5-FU plus sandostatin on apoptosis in
      breast cancer. METHODS: Breast cancer samples from 16 patients were treated with
      5-FU (10 microg/ml) and sandostatin (0.1 microg/ml) in vitro using the in situ
      terminal deoxynucleotidyl transferase assay (TDT) to detect apoptosis. The
      patients were female (mean age 54.4 years). In the 16 patients, 10 had positive
      estrogen receptor (ER) and positive progestogen receptor (PR), and the rest had
      negative ER and PR. RESULTS: 18 hours after addition of 5-FU, sandostatin and
      both, the apoptotic rate of tumor cells was (21.8 +/- 6.6)%, (14.3 +/- 8.8)%, and
      (26.7 +/- 6.9)% respectively. When samples were divided into 2 groups according
      to the sensitivity of ER and PR, the apoptotic rate of 5-FU plus sandostatin was
      (32.2 +/- 7.9)%, in positive ER and PR group, but (20.5 +/- 5.5)% in negative ER
      and PR group (P < 0.05). CONCLUSIONS: 5-FU plus sandostatin is more sensitive in
      the positive ER and PR group than in the negative ER and PR group. 5-FU plus
      sandostatin would be helpful in the biotherapy of breast cancer patients with
      positive ER and PR.

PMID- 11829915
TI  - [The expressions of Fas and Fas-L in human breast invasive ductal carcinomas and
      their surrounding tissues].
AB  - OBJECTIVE: To study the relationship of the expression of Fas and Fas-L with the
      pathogenesis and differentiation of breast invasive ductal carcinomas. METHODS:
      Both carcinoma tissues and their surrounding tissues from 50 patients with breast
      invasive ductal carcinomas were studied for the expression of Fas and Fas-L by
      immunohistochemical staining. RESULTS: The expression level of Fas in breast
      ductal carcinoma was significantly lower than that of tissues surrounding
      carcinomas, and the expression level of Fas-L in breast ductal carcinoma was
      significantly higher than that of tissues surrounding carcinomas. There was no
      significant difference in the expression of Fas and Fas-L in carcinomas with
      different differentiation grades. CONCLUSIONS: The expression of Fas is
      downregulated and the expression of Fas-L is upregulated in human breast invasive
      ductal carcinomas. Human breast invasive ductal carcinomas may enhance their
      development through downregulating the expression of Fas and upregulating the
      expression of Fas-L. The expression level of Fas and Fas-L has nothing to do with
      the differentiation of human breast invasive ductal carcinomas.

PMID- 11829916
TI  - [Nosocomial catheter-related sepsis secondary to central venous catheters].
AB  - OBJECTIVE: To study bacteria and drug sensitivity of catheter-related sepsis
      (CRS). METHODS: Between February 1993 and December 1997, 52 patients with central
      venous catheter-related sepsis were studied retrospectively. RESULTS: The most
      common organisms were staphylococcus aureus and staphylococcus epidermis. The
      bacterial pathogens isolated demonstrated a marked pattern of antibiotic
      resistance. Gram-positive cocci were sensitive to vancomycin with a sensitivity
      of 93.3%, and gram-negative bacilli were sensitive to amikacin and ceftazidine
      with a sensitivity of 51.7%. CONCLUSIONS: The effective treatment of catheter
      related sepsis is removal of infected catheters. Vancomycin and (or) amikacin may
      be first chosen to treat CRS.

PMID- 11829917
TI  - [Diagnosis and surgical treatment of idiopathic slow transit constipation].
AB  - OBJECTIVE: To investigate the pathogenesis, the diagnostic criteria, and the
      therapeutic method of idiopathic slow transit constipation. METHODS: History
      recording, bowel transit, anorectal dynamic, electromyography of the pelvic floor
      and defecography were performed before subtotal or total colectomy for severe
      constipation resistant to conservative treatment. RESULTS: The natural stool
      frequency was decreased and the time of bowel transit was delayed. The rectal
      sensation and the ability to reflect inhibition of the pelvic floor when
      attempting to defecate were damaged significantly compared with normal controls.
      pathological findings showed that the argyrophilic neurons in the myentenic and
      submucous plexus reduced quantitatively. All the patients were followed up for an
      average of 32.2 months. Satisfactory functional outcome was obtained in 91.8% of
      the patients receiving the operation. CONCLUSIONS: The severe damage colon
      transit function is due to the impairement of the myentenic and submucous plexus
      of the colon. It causes vary. The diagnosis of the disease is dependent on the
      typical clinic features and the bowel transit test. The symptoms of constipation
      could be relieved effectively by removal of the pathologic colon.

PMID- 11829918
TI  - [Dynamic monitoring of serum soluble HLA class I antigens in renal transplant
      recipients].
AB  - OBJECTIVE: To investigate the relations between serum soluble HLA class I
      antigens (sHLA-I) and the period of acute rejection and infection in renal
      transplant recipients. METHODS: We measured the serum levels of sHLA-I in 36
      renal transplant recipients with ELISA dynamically. RESULTS: The serum sHAL-I
      levels were higher in uremia patients than in normal controls [(2.94 +/- 0.34)
      microg/L vs. (0.76 +/- 0.33) microg/L, P < 0.05]. After renal transplantation,
      the serum sHLA-I levels decreased significantly in stable patients [(0.63 +/-
      0.33) microg/L], but increased significantly 3 days before acute rejection and 5
      or 7 days after infection. CONCLUSIONS: The serum sHLA-I levels can be used as a
      parameter for monitoring acute rejection and infection in renal transplantation.

PMID- 11829919
TI  - [Clinical protocols for the treatment of severe acute pancreatitis].
AB  - OBJECTIVE: To set up principles for the treatment of severe acute pancreatitis
      (SAP). METHODS: The therapeutic principles and results of SAP in three periods
      were analyzed. Period I (1980 - 1990) was characterized by early surgical
      intervention supplemented with integrated traditional and western medical
      therapy, period II (1991 - 1993) by integrated traditional and western medical
      therapy supplemented with surgery for early complications, and period III (1994 -
      1997) by integrated traditional and western medical therapy supplemented with
      surgery for local infectious complications only. RESULTS: Because of the
      improvement of intensive care, the operation rates kept declining in the three
      periods. They were 77.59%, 54.55% and 29.55% with a mortality rate of 40.52%,
      17.17% and 11.36%, respectively. CONCLUSIONS: Integrated traditional and western
      medicine has been effective in most SAP patients, and surgery is indicated only
      for late complications such as necrotizing infection. Early surgery should be
      restricted.

PMID- 11829920
TI  - [Surgical treatment of Ebstein's malformation: report of 108 cases].
AB  - OBJECTIVE: To review retrospectively the experience of surgical treatment of
      Ebstein's malformation in 108 patients. METHODS: One hundred and eight patients
      with Ebsteins malformation underwent surgical correction, including tricuspid
      valve annuloplasty in 83 patients (73.4%) and tricuspid valve replacement in 30
      (5 with redo-operation). Concomitant procedure included division of the abnormal
      accessory conduction pathway in 8 patients. RESULTS: The overall hospital
      mortality was 8.8%. The hospital mortality rate was 10.4% before 1990 and 5.5%
      after that time. There was a significant difference between the two periods (P <
      0.05). The main causes of death were low cardiac output, arrhythmias and right
      heart failure. The mean follow-up time was 6.3 years. The heart function improved
      to be NYHA class I or II in 92% of the patients. CONCLUSIONS: Early surgical
      intervention is recommended for patients with Ebstein's malformation, especially
      for those with symptoms and cardiac enlargement. Tricuspid valve repair should be
      performed if anterior leaflet of the tricuspid valve well developed. However,
      tricuspid valve replacement is advocated if anterior leaflet is dysplastic or its
      origin displaced.

PMID- 11829921
TI  - [Early results of 1,110 cases of coronary artery bypass].
AB  - OBJECTIVE: To introduce our experience with Coronary artery bypass. METHODS: From
      January 1996 to March 1999, coronary artery bypass was in 1110 patients at our
      hospital. They were 985 men and 125 women, aged 27 - 78 years (57 +/- 9). 500
      patients were aged over 60 years. 670 patients had a history of myocardial
      infarction. 450 patients suffered from instable, and 460 from stable angina. 169
      patients had stenosis of the left main trunk (>or= 50%). The heart function of
      240 patients was over NYHA class III, the EF of 123 patients was less than 40%.
      454 patients were associated with hypertension, 133 with diabetes, 131 with
      ventricular aneurysm, 48 with valvular disease, and 5 with rupture of ventricular
      septal. 1048 procedures were performed on hypothermia cardiopulmonary bypass
      (CPB) and 60 on beating heart. Myocardial preservation was carried out by cold
      blood cardioplegia with potassium. The average time of CPB was 115 +/- 35
      minutes, and that of aortic cross clamp was 72 +/- 24 minutes 110 cases received
      one graft, 145 cases two grafts, 415 cases three grafts, and 439 cases four and
      more than four grafts. Left internal mammary artery, great saphenous vein, and
      radial artery were used as coronary artery bypass conduits on 751, 877 and 101
      patients, respectively. Total arterial myocardial revascularization was performed
      on 72 patients. Concomitant operation included ventricular aneurysmetomy (112
      cases), plication (14), left ventriculoplasty (5), valvular procedures (48),
      repair ventricular septal rupture (5). RESULTS: 1 101 patients were discharged
      uneventfully. Early death occurred in 9 patients, (0.81%). Complication included
      low cardiac output (11 cases), introaortic balloon pump (7), perioperative
      myocardial infarction (2), complication of brain (3), and rethoractomy for
      bleeding (4). CONCLUSIONS: To identify adequate target vessel and completely
      revascularize ischemic myocardium are the key of coronary artery bypass.
      Perioperative treatment is important.

PMID- 11829922
TI  - [Transpetrosal presigmoid approach for removal of giant petroclival tumors].
AB  - OBJECTIVE: To discuss the operative technique, advantage and postoperative
      complications in 41 patients with giant petroclival tumors treated with the supra
      and infratentorial transpetrousal presigmoid approach. METHODS: Clinical data
      were obtained from the review of charts and radiographic images of the 41
      patients after operation with temporo-occipotal free osseous flap, partial
      petrosectomy and mastoidectomy were performed around the labyrinth. The
      semicircular canals, cochlea and tympanic cavity were protected during the
      operation. After the super petrous was ligated and cut off, the petroclival
      region in front of the sigmoid sinus was exposed. RESULTS: In the 41 patients 20
      had meningiomas, 20 epidermoid cysts, and one schwannoma. Total resection was
      performed in 34 patients, subtotal resection in 16, and greater partial resection
      in one. Major postoperative complications included temporal aphasia (10
      patients), cerebral edema (6), brain stem infarct (2), IIIth, VIIth, VIth and
      posterial group cranial nerves palsies (16, 16, 8, 6 respectively), and
      cerebrospinal fluid leakage (4 cases). CONCLUSIONS: This approach can expose
      sufficiently the petroclival region. It can also reveal the area of adjacent
      sella, interpeduncular and formen magnum, and homolateral III-XIIth cranial
      nerves. The postoperative complications may be related to operative techniues and
      tumorous characteristics.

PMID- 11829923
TI  - [Acute rupture of anterior cruciate ligament: diagnosis and treatment by early
      arthroscopy].
AB  - OBJECTIVE: To early diagnose and treat acute rupture of anterior cruciate
      ligament (ACL). METHODS: 23 patients with acute rupture of ACL were examined and
      treated by early arthroscopy. RESULTS: The preoperative diagnosis of ACL rupture
      was similar to that of in 18 patients. Three patients were confirmed by early
      arthroscopy and 2 patients were found to have ACL rupture, 16 patients were
      combined with meniscus injuries and 6 patients with cartilaginous injuries.
      Patholanatomical type of ACL were rupture of parenchymal part (21 patients) and
      avulsion rupture of attachment point (2 patients). In 6 patients ACL was
      reconstructed under arthroscope. CONCLUSIONS: Early arthroscopy in the treatment
      of acute ACL rupture has advantages of minor injury, correct diagnosis, visible
      location of injury or combined injury and timely treatment. Early arthroscopy for
      acute ACL rupture is an important measure for diagnosis, treatment, and
      stabilization of the knee joint.

PMID- 11829924
TI  - [Atypical pheochromocytoma].
AB  - OBJECTIVE: To improve the diagnosis and treatment of atypical pheochromocytoma.
      METHODS: 51 cases of pheochromocytoma were treated from July 1985 to August 1998.
      RESULTS: Of the 51 cases, 19 were atypical, and were characterized by silent
      tumor, pheochromocytoma in pregnancy, bilateral tumor, extraadrenal tumor,
      malignant tumor, and recurrent tumor. Open operation was performed for all kinds
      of cases in accordance with their special characteristics. CONCLUSIONS: Surgical
      extirpation is the only means for the treatment of atypical pheochromocytoma and
      meticulous perioperative management is essential.

PMID- 11829925
TI  - [Nutritional impact of glycyl-glutamine dipeptide on the autotransplanted small
      intestine in pig].
AB  - OBJECTIVE: To observe the impact of glycyl-glutamine (Gly-Gln) dipeptide on the
      autotransplanted small bowel. METHODS: Ten unbred pigs underwent small bowel
      autotransplantation and were divided randomly into two groups: GTPN and STPN. In
      the GTPN group (n = 5), the pigs received TPN supplemented with Gly-Gln for 28
      days, whereas in the STPN group (n = 5), the pigs received isonitrogenous and
      isocaloric standard TPN for 28 days. The content of plasma glutamine (Gln), the
      concentrations of mucosal Gln, protein, villous DNA and RNA, villous height,
      mucosal thickness, crypt depth, villous surface area, D-xylose absorption test,
      and intestinal permeability to (99m)Tc-DTPA were measured on the operative day or
      on the 1st and 28th day after operation. RESULTS: All the indexes except the
      intestinal permeability (IP) to (99m)Tc-DTPA were significantly higher in the
      GTPN group than in the STPN group (P < 0.05) on the 28th day after operation, but
      the IP to (99m)Tc-DTPA was significantly lower in the GTPN group than in the STPN
      group (P < 0.05). CONCLUSIONS: Gly-Gln has special nutritional effect in
      improving the metabolism, structure and function of autotransplanted small
      intestine in pig.

PMID- 11829926
TI  - [Safety of direct gene transfer into rat carotid arteries mediated by adenoviral
      vector].
AB  - OBJECTIVE: To evaluate the safety of direct gene transfer into rat carotid
      arteries mediated by adenoviral vector. METHODS: After being soaked in high
      concentration of glucose solution containing Adv5-CMV (control group) or Adv5
      CMV/LacZ (treatment group) for 30 minutes, soluble stents were inserted into the
      lumina of rat carotid arteries and end-to-end anastomoses of cut rat carotid were
      performed with standard microvascular surgical technique. On the 7th day after
      surgery, anastomotic carotid arteries of the two groups were obtained, and
      samples of ascending aortas, hearts, brains, livers, lungs, spleens and kidneys
      of the treatment group were taken for assessing beta-galactosidase activity and
      histochemical staining. RESULTS: Beta-galactosidase activity was not detected in
      the carotid arteries in the control group and in those organs not directly
      exposed to adenoviral vector in the treatment group. The amount of beta
      galactosidase expression in the carotid arteries in the treatment group was 10.1
      x 10(-3) IU/g tissue. Microscopic examination of sections from vessels in the
      control group and from the aorta, heart, brain, liver, lung, spleen or kidney in
      the treatment group revealed no X-gal staining. Microscopic examination of the
      carotid arteries in the treatment group revealed blue-staining in all anastomotic
      arteries and in all layers of the arterial wall, including the intima, media, and
      adventitia. CONCLUSIONS: A recombinant gene could be safely delivered to a local
      site of the vessel by means of infection with adenoviral vector.

PMID- 11829927
TI  - [Combined use of rhBMP2/BCB and free periosteum in repairing segmental defects in
      radii of rabbits].
AB  - OBJECTIVE: To study the efficacy of combined use of rhBMP2/BCBand free periosteal
      graft in repairing segmental bony defects. METHODS: A new grafting material
      (rhBMP2/BCB) was made by combining recombinant human BMP2 (rhBMP2) and an antigen
      free bovine cancellous bone (BCB) as a carrier. rhBMP2/BCB was used alone in
      conjunction with free periosteal graft to repair a 1.5 cm defect in the radius of
      the rabbit. The defect-repairing capability for each of the treatment modalities
      was assessed radiographically, biomechanically, and by densitometry and
      histological studies. RESULTS: rhBMP2/BCB used alone was capable of healing the
      defect in large by 16 weeks, with a similar repair process and mechanism seen
      with RBX. Combined use of rhBMP2/BCB and free periosteal graft was superior in
      terms of increased amount and quality of the new bone formed at the early stage
      of the repair process (within 12 weeks) to rhBMP2/BCB used in isolation, with the
      defect basically healed by 12 weeks. CONCLUSIONS: Both methods are effective in
      repairing segmental bony defects, with rhBMP2/BCB used in conjunction with free
      periosteal graft being most preferred, considering the satisfactory osteogenesis,
      osteoconduction and osteoinduction.

PMID- 11829928
TI  - [Experimental study of radiofrequency thermocoagulation and applied anatomy of
      posterior rami of lumbar nerves].
AB  - OBJECTIVE: To determine points of radiofrequency thermocoagulation of the
      posterior rami of the lumbar nerves and to choose an effective temperature at
      which the conduction of painful impulse can be blocked. METHODS: The posterior
      rami of the lumbar nerves were dissected in 15 corpses of adults. The
      ultrastructure of nerve fibres, changes of sensary conduction velocity (SCV) and
      the waveform of the unmedullated fibres which conduct painful impulse (c wave)
      were observed after the sciatic nerves of rabbits were coagulated at various
      temperatures (60 degrees C, 70 degrees C, 80 degrees C, 90 degrees C). RESULTS:
      "Transverse Process Root Area" and "Transverse Process Point" can be regarded as
      primary marks of thermocoagulation of the posterior rami of the lumbar nerves.
      Stimulation of square-wave can make the location more accurate. While the
      temperature of thermocoagulation reached 80 degrees C, none of painful afferent
      nerve fibres survived. CONCLUSIONS: With accurate location and good control of
      temperature, radiofrequency thermocoagulation will be an effective therapy for
      the patients suffering from pain resulted from pathological changes of the
      posterior rami of the lumbar nerves.

PMID- 11829930
TI  - [The effect of early escheractomy on expression of ICAM-1 and E-selectin mRNA of
      endothelial cells].
AB  - OBJECTIVES: To examine the effect of burned serum on change in endothelial cell
      ICAM-1 and E-selectin mRNA expression and whether these alterations can be
      corrected by the means of escharectomy during burn shock period. METHODS: One
      hundred and seventy-six Wistar rats with 30% III degree TBSA on back were
      studied. Endothelial cell ICAM-1 and E-selectin mRNA were tested with the method
      of RT-PCR. RESULTS: ICAM-1 and E-selectin expression showed an increase after
      stimulation by serum of 4 hours post burn, reaching peak levels 168 hours after
      injury. ICAM-1 and E-selectin expression levels could decrease to baseline within
      168 hours in the rats which underwent escharectomy during shock stage, but kept
      higher than normal in rats without escharectomy or underwent 96 hours post burn.
      CONCLUSIONS: These findings suggest that eschar can induce endothelial cells to
      express adhesion molecule. Early escharectomy is important to prevent adhesion
      molecule expression and SIRS.

PMID- 11829929
TI  - [Effect of escharectomy during burn shock stage on stress response].
AB  - OBJECTIVE: To investigate changes in hormones of plasma and the effect of
      escharectomy during burn shock stage on early stress response after burn.
      METHODS: Sixteen male minipigs were subjected to a 35% TBSA III degree burn
      injury. The burned minipigs were randomly divided into two groups: escharectomy
      during burn shock stage group (S group) and escharectomy group after burn shock
      stage (N group). The sequential changes in plasma levels of insulin, glucagon,
      cortisol, GH, IGF-I, albumin were analyzed. RESULTS: The serum concentration of
      insulin, glucagon, cortisol increased to some degree, whereas the serum
      concentration of GH, IGF-I decreased obviously after burn. As compared with the N
      group, no significant difference in the serum concentration of glucagon,
      cortisol, GH, IGF-I, was observed. CONCLUSIONS: Escharectomy during burn shock
      stage could not aggravate stress response after burn.

PMID- 11829931
TI  - [A scanning method for detecting colorectal tumors].
AB  - OBJECTIVE: To develop a method for survey of colorectal tumors. METHODS: Mucus
      obtained by digital rectal examination was smeared on a slice to react with
      peanut agglutinin labeled by Horseradish-peroxidase. RESULTS: Brown color was
      noted in positive reaction. In detecting colorectal tumors, the sensitivity and
      specificity of the method was 88.2% and 92.5% respectively. CONCLUSION: The
      method is effective in detecting colorectal tumors in humans.

PMID- 11829932
TI  - [Lymphoscintigraphy: evaluating lymphatic spread of rectal cancer].
AB  - OBJECTIVE: To investigate lymphatic drainage of rectal and lymphatic spread of
      rectal cancer. METHODS: Rectal endoscopic lymphoscintigraphy was performed in 37
      volunteers and 16 patients. One millilitre dextran marked with (99m)Tc was
      injected bilaterally into submucosa of the rectum through rectal endoscopy. 1, 2,
      3 hours after the injection, rectal lymphoscintigraphy was registered with a
      computerized gamma camera (TOSHIBA GCA901A). RESULTS: Lymphoscintigraphy in
      control subjects showed upward epirectal and pararectal nodes. The average number
      of the nodes was 12 three hours after the injection. Compared with histological
      node examination in all patients operated upon for rectal cancer, rectal
      endoscopic lymphoscintigraphy showed a sensitivity of 97.1%, a specificity of
      75.0%, an overall accuracy of 87.5%, a false positivity of 25.0%, and false
      negativity of 8.3%. CONCLUSION: The method is better for evaluating lymphatic
      spread of rectal cancer before operation.

PMID- 11829933
TI  - [Gamma delta T cells and their receptor Vdelta gene rearrangement in transitional
      mucosa of rectal carcinoma].
AB  - OBJECTIVE: To observe gamma delta T cells and their receptors Vdelta gene
      rearrangement expression in the transitional mucosa of rectal carcinoma, and to
      investigate their relations with local tumor recurrence. METHODS: In 13 patients
      with rectal carcinoma, gamma delta T cells in transitional mucosa were measured
      with two-color immunofluorescent flow cytometric analysis and polymerase chain
      reaction technique. RESULTS: The volume of gamma delta T cells in transitional
      mucosal lymphocytes (TML) were significantly higher than that in tumor
      infiltrating lymphocytes (TIL), and significantly lower than that in normal
      intestinal epithelial lymphocytes (IEL) (P < 0.05). The gamma delta T cell
      receptors delta chain V region (gamma delta-TCR Vdelta1-Vdelta6) gene
      rearrangement was all expressed in TIL, TML and IEL; but the Vdelta 6 gene
      expression in both TML and TIL were higher than that in IEL (P < 0.05).
      CONCLUSIONS: The decreased volume of gamma delta T cells in TML resulted in
      decreased local immune function and may be responsible for the local tumor
      recurrence after resection. The high expression of Vdelta 6 gene rearrangement in
      both TIL and TML suggests the skewing of gamma delta-TCR receptors and the
      abtitumor specificity of TIL and TML in local epithelium.

PMID- 11829934
TI  - [Relationship between insulin-like growth factor II and prognosis of colorectal
      cancer].
AB  - OBJECTIVE: To investigate the relationship between insulin-like growth factor II
      (IGF-II) and prognosis of colorectal cancer. METHODS: One hundred and forty-two
      colorectal cancer patients were enrolled. In colonoscopic biopsy specimens, the
      expression of IGF-II and PCNA were detected immunohistochemically, while TUNEL
      technique was used to detect apoptosis. All patients were followed up, and
      disease-free survival (DFS) and overall survival (OS) rate were calculated.
      RESULTS: The expression level of IGF-II was significantly higher in colorectal
      cancer than in normal colorectal mucosa. A correlation was observed between more
      IGF-II expression, high PCNA labeling index, and apoptotic index was
      demonstrated. Patients with lower expression level of IGF-II had higher DFS and
      OS. Multivariate analysis by means of the Cox proportional-hazards model revealed
      that the expression level of IGF-II was an independent prognostic predictor in
      colorectal cancer patients. CONCLUSION: The expression level of IGF-II is a new
      prognostic predictor for colorectal cancer.

PMID- 11829935
TI  - [Colorectal cancer: lymphatic metastasis and choice of operation].
AB  - OBJECTIVE: To study lymphatic metastasis of colorectal cancer for deceding the of
      dissection extent of dissection. METHODS: Six hundred and twenty-three lymph
      nodes from 74 cases of colorectal cancer were analyzed after D(3) resection. They
      were classified into peritumor, longitudinal spread, and upward spread groups.
      The metastasis rate of lymph node and its incidence were calculated. RESULTS: The
      metastasis rate of lymph node and its incidence in the peritumor, longitudinal
      spread, and upward spread (N(2) and N(3)) groups were 47.2% and 38.6%, 22.8% and
      18.6%, and 29.7% (20.3% and 9.4%) and 10.2% (19.0% and 5.3%), respectively. The
      distribution rate of metastatic lymph node was 61.2%, 17.1%, and 21.6% in the
      peritumor, longitudinal spread, and upward spread groups, respectively. Within
      2.0 cm on the anal side of rectal cancer, the metastasis rate was 3.7%, whereas
      in 2.0 - 4.0 cm no metastasis was observed cancer at the lower part of the rectum
      demonstrated a higher lateral metastasis rate. CONCLUSIONS: Colorectal cancer
      tends to metastasize to longitudinal and the risk of metastasis increased in the
      stage of pT(3) and pT(4) or low differentiation stage. Jump metastasis is also a
      feature. D(3) radical resection is necessary for colorectal cancer, but extended
      lateral lymph node needs enectomy or total mesorectal excision. No residual tumor
      tissue exists at the anastomosis site after low anterior resection when the
      excision distance is beyond 2.0 cm from the anal margin of rectal cancer.

PMID- 11829936
TI  - [Selective arterial embolization for the treatment of thoracolumbar spinal
      tumor].
AB  - OBJECTIVE: To decrease intraoperative blood loss during tumor resection. METHODS:
      Fifteen patients with primary thoraco-lumbar spinal tumor [giant cell tumor (5
      patients), malignant nerinoma (2), chordoma (1), fibrous xanthosarcoma (1),
      malignant fibrohistocytoma (1), osteosarcoma (1), Ewing sarcoma (1), myeloma (1),
      leimyosarcoma (1), Non-Hodgkin diseases (1)] were treated by means of
      preoperative selective arterial embolization, tumor resection, and spinal
      reconstruction. Eight patients were subjected to total spondylectomy in one
      stage. RESULTS: Fourteen patients showed satisfactory results after embolization.
      The volume of intraoperative blood loss ranged from 3,000 ml to 400 ml (average
      1,200 ml). Follow up of the patients varied from 8 months to 19 years (average
      48.7 months). Local recurrence happened in 3 patients; 3 patients died from
      metastasis. Three of 4 patients recovered from complete bowel movement and
      urination. Seven of nine patients had musical strength improved. Six of 8
      patients had recovery of the e sensation of the lower limbs. CONCLUSIONS:
      Selective arterial embolization before operation followed by operation within 24
      hours can reduce intraoperative blood loss, shorten operative time, and provide a
      clear operative field for tumor resection.

PMID- 11829937
TI  - [Allograft-prosthesis combination in limb salvage surgery].
AB  - OBJECTIVE: To study allograft-prosthesis combination in limb salvage and the
      rational of composite prosthesis. METHODS: Of 16 patients with bone tumors age
      from 19 to 60 years, 6 women 12 men, osteosarcoma was found in 4 patients,
      chondrosarcoma in 2, malignant giant cell tumor in 3, fibrosarcoma in 3, and
      other malignant bone tumor in 4. Allograft-prosthesis combination in included
      allograft proximal femurs with total hip arthroplasty (3 patients), allografts
      bipolar femoral head replacement (8), allografts with total knee arthroplasty
      prosthetic replacements (7). All patients received adjuvant therapy for tumor
      control. RESULTS: The length of follow-up ranged from 18 months to 5 years during
      which time 1 patients died, 3 survived as tumor-carriers, and 12 were disease
      free. All patients obtained better functional result in their extremities and had
      good quality of life. CONCLUSIONS: Both prosthetic replacement and allograft
      advantages, the use of large bone allografts with metallic prosthesis for the
      treatment of bone tumors near or involving joints can be applied with good
      results in selected patients having limb salvage surgery.

PMID- 11829938
TI  - [Curettage plus cement reconstruction for treating giant cell tumor of limbs].
AB  - OBJECTIVE: To evaluate curettage plus cement reconstruction in the treatment of
      giant cell tumor (GCT) of limbs. METHODS: 125 patients with GCT of limbs were
      treated with curettage plus cement reconstruction. They were 62 men and 63 women
      aged from 12 to 71 years, 101 patients had primary GCT and 24 had recurrence of
      GCT. The recurrence at the knee was noted in 100 patients (80%). RESULTS: 125
      patients were followed-up for 96 months (range 13 - 194 months). The recurrence
      rate was 12.7% in the primary group and 10.3% in the recurrent group. Two
      patients were infected. Joint functions were excellent. CONCLUSIONS: Curettage
      plus cement reconstruction is safe and effective in treating local GCT of limbs.
      The key the method is aggressive curettage of the lesion via a bone window.
      Cement is adjuvant therapy only.

PMID- 11829940
TI  - [Flow cytometry for testing chemosensitivity of malignant bone tumors].
AB  - OBJECTIVE: To study chemosensitivity and multidrug resistance of malignant bone
      tumors and to make an individual protocol of chemotherapy with sensitive
      antitumor agents. METHODS: Apoptosis induced by MTX, ADM, MMC, VP-16, VCR and
      CTX, and chemosensitivity in 32 fresh specimens of malignant bone tumors were
      analyzed by flow cytometry (FCM) and quantitative immunofluorescence. The
      expression of P-glycoprotein (P170) in the specimen and the relation between
      P170, multidrug resistance, and chemosensitivity were detected. RESULTS: The rate
      of apoptosis was significantly different in malignant bone tumor cells treated
      with different drugs: MTX (30.50 +/- 10.22)%, ADM (26.28 +/- 9.35)%, MMC (23.11
      +/- 7.38)%, VP-16 (18.17 +/- 6.14)%, VCR (4.44 +/- 2.55)%, and CTX (1.22 +/-
      0.59)%. The individual variation of cell apoptosis was prominent in the specimens
      of same pathological type treated with same agent. There was lower
      chemosensitivity in the malignant bone tumors with a high expression of P170.
      CONCLUSIONS: Chemosensitivity testing by flow cytometry is a simple, quick and
      sensitive assay. Quantitative analysis of expression of P170 could be used to
      predict multidrug resistance and its chemosensitivity of malignant bone tumors.

PMID- 11829939
TI  - [Expression and regulation of p16 in osteosarcoma].
AB  - OBJECTIVE: To study the expression and regulation of p16 and related factors in
      osteosarcoma. METHODS: The levels of p16 protein and related factors were
      explored by Western blot analysis in 12 cases of osteosarcoma tissues and in
      cells of different phases of osteosarcoma cell line OS732. The status of p16
      protein in osteosarcoma cells was revealed by immunofluorescence analysis.
      RESULTS: p16 protein was detected in 10 of 12 osteosarcoma tissues. pRb was found
      in all of the specimens, but 8 of them were hyperphosphorylated. p16 protein was
      the least in G1 phase. Localized in cytoplasm during G1 phase, p16 protein
      gathered around nuclear envelope in S phase and entered the nucleus in G2 phase.
      CONCLUSIONS: The expression rate of p16 protein was 83.3% in osteosarcoma
      tissues. The expression of p16 protein was unable to inhibit the phosphorylation
      of pRb in most osteosarcomas; p16 protein was extremely low in G1 phase,
      presumably it was sufficient to inhibit the phosphorylation of pRb, causing
      abnormal proliferation of the cells.

PMID- 11829941
TI  - [Gene expression of TGF-beta1 and its type II receptor in hepatocellular
      carcinoma].
AB  - OBJECTIVE: To investigate the gene expression of transforming growth factor-beta1
      (TGF-beta(1)) and its type II receptor (TGF-beta R II) in hepatocellular
      carcinoma. METHODS: The expression of TGF-beta(1) and TGF-beta R II at mRNA level
      and protein level in 30 cases of HCC was separately detected using reverse
      transcription-PCR and immunohistochemistry technique. RESULTS: There was no
      difference in the expression of TGF-beta(1) at mRNA level between HCC tissue
      (24/30) and surrounding liver tissue (26/30). At the protein level, however, the
      expression of TGF-beta(1) decreased in HCC tissue compared with that in the
      surrounding liver tissue (P < 0.01). The expression of TGF-beta R II mRNA
      decreased significantly in HCC tissue (11/30) compared with that in the
      surrounding liver tissue (23/30) (P < 0.01). The less HCC expressed TGF-beta R II
      mRNA, the poorer the tumoral hepatocytes differentiated (P < 0.01) and the more
      likely the portal vein metastasis and cancer embolus appeared (P < 0.05).
      CONCLUSIONS: In the negative growth regulation of tumoral hepatocytes by TGF
      beta(1), two defects take place: the expression of TGF-beta(1) at the protein
      level and the expression of TGF-beta R II at the mRNA level.

PMID- 11829943
TI  - [Lutembacher's syndrome].
AB  - OBJECTIVE: To compare classical and acquired Lutembacher's syndrome (mitral
      restenosis after percutaneous balloon mitral valvuloplasty) in attempt to know
      their different in pathophysiology, diagnosis, and surgical treatment. METHODS:
      The data from 22 cases of classical and acquired Lutembacher's syndrome who
      underwent surgical treatment in the same period were analyzed. RESULTS: No death
      occurred in the classical group. In the acquired group the mortality however was
      42.8% for those highly complicated with pulmonary hypertension and right heart
      failure. CONCLUSIONS: Classical Lutembacher's syndrome can be corrected
      satisfactorily. The acquired one deteriorates rapidly with severe pulmonary
      hypertension and right heart failure, and needs early surgical intervention
      reduce the operation mortality.

PMID- 11829942
TI  - [Hepatic arterial infusion of 32P-radionuclide microspheres for radiation therapy
      of hepatocellular carcinoma].
AB  - OBJECTIVE: To investigate the efficacy of internal radiation of (32)P-glass
      microspheres ((32)P-GMS) in unresected hepatocellular carcinoma (HCC) via
      subcutaneous arterial port. METHODS: Hepatic arterial (99)technetium
      macroaggregate albumin ((99)Tc-MAA) scanning via subcutaneous arterial port was
      undertaken to measure lung/liver shunting ratio and tumor/liver ratio. Hepatic
      arterial infusion of (32)P-GMS was performed in 17 cases of HCC with a dose from
      1.11 to 1.30 GBq. Twenty cases of HCC undergoing hepatic arterial
      chemoembolization (HACE) in the same period served as controls group. RESULTS:
      There was no treatment-related death in the 17 cases. In 7 of the 17 cases, AFP
      level and/or tumor size decreased by 50% after treatment, with a response rate of
      64.7%. The median survival time was 5.5 months, and the 3-, 6-, 9-, 12-month
      survival rates were 94.1%, 44.1%, 31.0%, 24.4%, respectively. The therapeutic
      efficacy was better than that of HACE. The survival time was significantly longer
      in patients with T/N ratio >or= 2 than in those with T/N < 2 (P < 0.05).
      CONCLUSIONS: Hepatic arterial infusion of (32)P-GMS is an alternative treatment
      for unresected HCC.

PMID- 11829944
TI  - [Cardiac metal foreign body: analysis of 21 cases].
AB  - OBJECTIVE: To improve early diagnosis and clinical treatment of metal foreign
      body in the heart. METHODS: In 21 patients, case history, clinical manifestation,
      chest X-ray film, and echocardiograph were reviewed. 20 patients received
      operation: emergency exploration (13) and elective operation (7). Four patients
      were subjected to cardiopulmonary bypass. The other one was not operated on
      because of absence of symptoms and small foreign body. Foreign bodies mostly
      bullets, were usually located in the right ventricle. Ventricular fibrillation
      occurred in 3 patients during operation, two of them were resuscitated. RESULTS:
      20 patients but one recovered, a mortality rate of 5%. CONCLUSIONS: Early
      diagnosis, rapid management, and localization of foreign body are essential to
      the selection of treatment.

PMID- 11829945
TI  - [Posttraumatic or inflammatory acute respiratory distress syndrome on high
      altitude area: a retrospective analysis of 94 deaths due to ARDS/MOF].
AB  - OBJECTIVE: To determine the characteristic predictors of acute respiratory
      distress syndrome (ARDS) in the high altitude area of China. METHODS: According
      to the diagnostic criteria of ARDS, 2 325 cases were screened in the recent 10
      years. Except malignant tumors, cardio-cerebrovascular diseases, chronic
      obstructive pulmonary disease, and chronic multiple organ failure, the causes of
      death were analysed retrospectively. RESULTS: 94 cases (4.04%) were diagnosed as
      ARDS, but in the primary case record, only 27 cases (1.16%) had been diagnosed as
      ARDS/MOF. Of the 94 ARDS patients, 79 complicated by extrapulmonary organ damage
      involving the kidney, heart, liver, gastro-intestinal tract, and brain. A total
      of 305 organs were involved (average 3.24 organs each case). Lung failure only
      accounted for 15 cases. CONCLUSIONS: The combination of the diagnostic criteria
      of ARDS for high altitude area and flate area, injury severity scale, blood gas
      monitoring, and integrated traditional Chinese medicine and western medicine may
      improve the prognosis of ARDS.

PMID- 11829946
TI  - [Refractory carotid-cavernous fistula: causes and countermeasures].
AB  - OBJECTIVE: To explore the causes and countermeasures of refractory carotid
      cavernous fistula (CCF). METHODS: Twelve refractory cases from 123 cases of
      consecutive traumatic CCF during 12 years were reviewed. RESULTS: The main causes
      of refractory CCF were: small or large fistula's opening, or constrictive parent
      artery; inappropriate early treatments such as ligature of internal carotid
      artery or common carotid artery, balloon detachment of, and non-dense packing of
      coils inside the cavernous sinus; unexpected deflation or balloon displacement of
      resulting in fistula recurrence. Anatomical cure was achieved in 11 cases, and
      clinical care in 1 by using balloon or/and coil or/and NBCA (n-butal 2
      cyanoacrylate) through arterial, venous or surgical approach. CONCLUSIONS:
      refractory CCF can be treated effectively skilled catheterization and
      embolization as well as appropriate approach and embolic material according to
      fistula structure and vascular route.

PMID- 11829947
TI  - [Orbito-zygomatic approach for removal of tumors of the skull base].
AB  - OBJECTIVE: To evaluate the advantages and indications of orbito-zygomatic
      approach for removal of tumors of the skull base. METHODS: Fifteen patients with
      tumors of the skull base were operated on using obito-zygomatic approach. The
      advantages and indications of the approach were evaluated. RESULTS: In 7 cases of
      meningioma, total removal of the tumor was achieved in 6 cases, and subtotal
      removal in 1. In 4 cases of craniopharyngioma, the tumor were totally removed in
      3 cases, and subtotally removed in 1. The tumor were totally removed in 2 cases
      of trigerminal neurilemoma and 1 case of germinoma. There was one operative
      death. All patients recovered except 3 who had minor extraocular parasis.
      CONCLUSIONS: This approach ensures additional space, and less cerebral retraction
      for easy access to skull base tumor, especially the large neoplasm of middle
      cranial base with or without orbital or posterior cranial base extension.

PMID- 11829948
TI  - [External adrenal pheochromocytoma].
AB  - OBJECTIVE: To improve the diagnosis of external adrenal pheochromocytoma.
      METHODS: From 1958 to 1998, 66 cases of external adrenal pheochromocytoma, 23.3%
      of pheochromocytomas, at the same period in the Department of Urology, RuiJin
      Hospital were reviewed. RESULTS: In the 66 cases, the malignant rate was high
      (33%). CONCLUSIONS: (131)I-MIBG is important in the diagnosis and treatment of
      external adrenal pheochromocytoma. Long-term follow up after operation is
      imperative to the cases of external adrenal pheochromocytoma.

PMID- 11829949
TI  - [Detection of telomerase activity in prostate needle-biopsy samples].
AB  - OBJECTIVE: To detect telomerase activity inprostate needle-biopsy samples and its
      role in diagnosis and prognosis of prostate cancer. METHODS: 20 tissue samples of
      prostate cancer tissues and 16 samples of adjacent tissues were obtained by
      needle-biopsy guided by transrectal B ultrasonography. 16 samples of benign
      prostatic hyperplasia tissues were obtained by prostatectomy and were confirmed
      pathologically. Telomerase activity was revealed by modified PCR-based telomeric
      repeat amplication protocol (TRAP)-silver staining assay. RESULTS: Telomerase
      activity was revealed in 18 cases of prostate cancer. In tissues adjacent to
      prostate cancer, telomerase activity was found in 7 of 11 cases of prostatic
      intraepithelial neoplasia (PIN), and in 2 of 5 cases of BPH. None of tissue
      samples from patients with BPH showed telomerase activity. CONCLUSIONS:
      Telomerase activity in prostate needle-biopsy samples might be an useful marker
      for detecting prostate cancer and biological malignancy.

PMID- 11829950
TI  - [Anaerobic infection and its rapid detection in surgical patients].
AB  - OBJECTIVE: To investigate anaerobic infection and its rapid detection in surgical
      patients. METHODS: 372 specimens were collected from surgical patients for
      anaerobe detection. To find a rapid detectable method, 110 specimens were
      collected for comparative studies by using indirect immunofluorescent antibody
      technique (IFA), enzyme labeled antibody technique (ELAT) and general cultural
      method (CM). RESULTS: The isolation rate of anaerobes was rather high in
      pyothorax (88.9%), abdominal abscess (86.7%), appendicitis (83.9%) and cerebral
      abscess (all five cases were positive). In burn wounds, the rate was about 23.6%
      especially in deep burn wounds. Among 212 strains detected, the predominant
      anaerobes were as follows B. melaninogenicus (28.8%), B. fragilis (25%), F.
      nucleatum (7.5%), C. perfringens (7.5%), and peptostreptococcus (5.7%); most of
      them (87.8%) were non-sporing anaerobes. Mixed infection with aerobes accounted
      for 64%. The survey of rapid detection was conducted in B. fragilis, B.
      melaninogenicus, C. perfringens, F. nucleatum and peptostreptococcus. The
      detectable rate was higher in IFA (79.1%) and ELAT (80.9%) than in CM (37.3%).
      CONCLUSION: IFA and ELAT might be rapid, specific, sensitive, and simple for
      detecting anaerobes.

PMID- 11829951
TI  - [Responses of normal rat kidney to different ischemic ways].
AB  - OBJECTIVE: To evaluate the effects of different ischemic ways on rat kidneys.
      METHODS: Male Wistar rat kidneys were divided into sham operation (group A),
      continuous ischemia (group B), intermittent ischemia (group C), ischemic
      preconditioning (group D), and delayed effect of ischemic preconditioning group
      (group E). The functional and morphologic changes and levels of MDA of the
      kidneys which suffered from different ischemia were assessed. RESULTS: The
      functional indexes of the group C were similar to that of the sham group. In the
      group B, D and E, the rats showed acute renal failure. Morphological findings
      showed that the groups B, D and E had severe tubular necrosis (+ + + - + + + +)
      24 hours after operation. The group C showed light tubular necrosis (+). 30
      minutes after reperfusion, the level of MDA was significantly lower in the group
      C than in the groups B, D and E (P < 0.01). CONCLUSIONS: In a given ischemic
      period, the injury effect of intermittent ischemia-reperfusion was much lower
      than that of continuous ischemia-reperfusion. Experimentally, ischemic
      preconditioning did not have protective effect on rat kidneys, including "classic
      protection" and "protection of second window". Intermittent ischemia-reperfusion
      did not increase OFR and lipid peroxidation injury.

PMID- 11829952
TI  - [Changes of PMN apoptosis in rabbits after burn].
AB  - OBJECTIVES: To study the dynamic changes of apoptosis of PMN from rabbits in the
      early stage after severe burn in vivo and investigate the effect of burn serum
      and wound exudate on PMN apoptosis in vitro. METHODS: 12 rabbits were randomly
      divided into 2 groups: control group (37 degrees C) and burn group (95 degrees C,
      15 sec, III degrees 30% TBSA). Whole blood from the burn group at 0, 4, 8, 12, 24
      h postburn was stained with acridine orange/ethidium bromide (AO + EB), and
      observed under UV microscopy. PMNs were isolated from both groups and cultured
      for 24 h (37 degrees C, 5% CO(2)) with normal serum (NS), burn serum (BS), and
      subeschar tissue fluid (STF) respectively. Morphological assessment and
      quantitation of apoptosis were performed with AO + EB stain and flow cytometric
      analysis. RESULTS: The number of apoptotic PMN in vivo decreased in the early
      stage postburn. In the BS + PMN group and STF + PMN group, the percentage of
      apoptotic PMN reduced (vs NS + PMN group, P < 0.05) and the specific DNA "ladder"
      pattern for apoptotic cells was not detected by agarose gel electrophoresis. We
      observed that both burn serum and STF could similarly suppressed PMN apoptosis
      while there was no significant difference between NS + normal PMN group and NS +
      burn PMN group. CONCLUSIONS: Apoptosis is inhibited in PMN from rabbits postburn
      in the early stage. Both burn serum and STF from rabbits postburn can inhibit PMN
      apoptosis in vitro.

PMID- 11830131
TI  - Transport of 1-kestose across the tonoplast of Jerusalem artichoke tubers.
AB  - The capacity for 1-kestose uptake into the vacuole of fructan storing Jerusalem
      artichoke tubers was investigated. 1-kestose serves both as building block for
      fructan initiation and as a fructose donor for chain elongation. Tonoplast
      vesicles were isolated from actively storing tubers, and their vesicles were
      capable of transporting sucrose in a manner indicative of a sucrose/H(+)
      antiport. Under similar conditions, 1-kestose was not taken up by vesicles
      energized by either a pH jump or in the presence of ATP. When added together at 2
      mM, sucrose uptake was not affected by the presence of 1-kestose. The data argues
      against the possible synthesis of 1-kestose in the cytosol and subsequent
      transport to the vacuole. The data also presents definite evidence for the
      existence a mechanism for sucrose accumulation in fructan storing vacuoles.

PMID- 11830132
TI  - Comparative subcellular immunolocation of polypeptides associated with xylan and
      callose synthases in French bean (Phaseolus vulgaris) during secondary wall
      formation.
AB  - The Golgi apparatus of plant cells is thought to be the main site of synthesis of
      cell wall matrix polysaccharides and the terminal glycosylation of glycoproteins.
      Much of this evidence still depends on earlier biochemical studies employing
      subcellular fractionation. However acquiring pure Golgi membranes is still
      difficult and the question of spatial organisation of glycosyl transferases can
      be addressed by immunolocation of the enzymes. An antibody to a xylan synthase
      associated polypeptide from French bean, the enzyme which synthesises the core
      polysaccharide for secondary wall xylan, has been raised and shown to inhibit its
      activity. Xylan is deposited in secondary thickenings and the xylan synthase was
      only detected in appreciable amounts in developing xylem cells. The location
      within the Golgi stack was observed throughout the dictyosomes. Some enzyme
      subunits were also detected in post-Golgi vesicles. A second antibody to a non
      catalytic M(r) 65000 subunit of beta 1,3- glucan (callose) synthase was used for
      a comparative study. Although the bulk of this enzyme has been detected in
      previous studies at plasmamembrane-wall interfaces in sieve plates and stressed
      tissue, a Golgi-location can be observed in root tip meristematic cells during
      cell plate formation. The enzyme was present throughout the stacks. Callose was
      also immunolocated in a similar manner to xylan in secondary walls and
      thickenings and in pits in developing xylem. In these cells, the callose synthase
      was detected at the surface of the growing thickenings and the plasmamembrane
      within the pits.

PMID- 11830133
TI  - Isolation and characterization of cDNA clones encoding ADP-glucose
      pyrophosphorylase (AGPase) large and small subunits from chickpea (Cicer
      arietinum L.).
AB  - Four cDNA clones encoding two large subunits and two small subunits of the starch
      regulatory enzyme ADP-glucose pyrophosphorylase (AGPase) were isolated from a
      chickpea (Cicer arietinum L.) stem cDNA library. DNA sequence and Southern blot
      analyses of these clones, designated CagpL1, CagpL2 (large subunits) and CagpS1
      and CagpS2 (small subunits), revealed that these isoforms represented different
      AGPase large and small subunits. RNA expression analysis indicated that CagpL1
      was expressed strongly in leaves with reduced expression in the stem. No
      detectable expression was observed in seeds and roots. CagpL2 was expressed
      moderately in seeds followed by weak expression in leaves, stems and roots.
      Similar analysis showed that CagpS1 and CagpS2 displayed a spatial expression
      pattern similar to that observed for CagpL2 with the exception that CagpS1 showed
      a much higher expression in seeds than CagpS2. The spatial expression patterns of
      these different AGPase subunit sequences indicate that different AGPase isoforms
      are used to control starch biosynthesis in different organs during chickpea
      development.

PMID- 11830134
TI  - Incorporation of [1-(13)C]1-deoxy-D-xylulose into isoprenoids of the liverwort
      Conocephalum conicum.
AB  - The incorporation of (13)C labeled 1-deoxy-D-xylulose into the monoterpene bornyl
      acetate, the sesquiterpene cubebanol, and the diterpene phytol has been studied
      in axenic cultures of the liverwort Conocephalum conicum. Quantitative (13)C NMR
      spectroscopic analysis of the labeling patterns of the sesquiterpene indicated a
      possible degradation of 1-deoxy-D-xylulose to acetate and subsequent
      incorporation via the mevalonic acid pathway. In bornyl acetate, the labeling
      occurred only in the acetate moiety whereas the isoprene units remained
      unlabelled. The isoprene units of the diterpene phytol showed incorporation of
      intact deoxy-D-xylulose. These results indicate the involvement of both IPP
      biosynthetic pathways and two independently operating compartments/cell types
      with MEP pathway machinery. One MEP compartment is presumably the plastid where
      phytol is formed; the second, involved in the build-up of the isoprene part of
      bornyl acetate, might be located in the oil cells. The acetylation of borneol to
      bornyl acetate in turn occurs in a cellular compartment that is not involved in
      the build-up of the isoprene units of borneol.

PMID- 11830135
TI  - Flavonoid 5-glucosides from the cocoon shell of the silkworm, Bombyx mori.
AB  - The flavonoid 5-glucosides, quercetin 5,4'-di-O-beta-D-glucopyranoside and
      quercetin 5,7,4'-tri-O-beta-D-glucopyranoside, together with the known quercetin
      5-O-beta-D-glucopyranoside, were isolated from the cocoon shell of the silkworm,
      Bombyx mori. The structures were identified by spectroscopic analysis. These
      flavonoid glucosides were not present in mulberry leaves, the silkworm's only
      food, and they are considered to be metabolites produced by the silkworm.

PMID- 11830136
TI  - Serine proteinase inhibitors in the Compositae: distribution, polymorphism and
      properties.
AB  - Multiple molecular forms of inhibitors of trypsin (TI) and chymotrypsin (CI),
      which are typical digestive enzymes of insects, mammals and micro-organisms, and
      subtilisin (SI), a proteinase of many bacteria and phytopathogenic fungi, were
      identified in seeds and vegetative organs of the majority of 128 wild and
      cultivated species representing 65 genera of three of the subfamilies of the
      Compositae. Inhibitors with M(r) ranging from 7450 to 7800 and combining
      activities towards subtilisin and trypsin and/or chymotrypsin (T/C/SI) had the
      widest distribution and may be involved in plant defense mechanisms. They were
      found in many species of the subfamilies Carduoideae (genera Carthamus,
      Centaurea, Cirsium), Cichorioideae (Lactuca, Taraxacum) and Asteroideae
      (Helianthus, Cosmos, Bidens). Partial amino acid sequencing showed that the
      safflower (Carthamus tinctorius) T/C/SI and Cosmos bipinnatus T/C/SI, T/SI and
      C/SI belonged to the potato I inhibitor family. The most active, variable and
      heterogeneous inhibitors were found in species of the tribe Heliantheae, which is
      placed in the evolutionary advanced subfamily Asteroideae. Seeds of Helianthus
      species, Eclipta prostrata, Gailardia aristata, Zinnia elegans and Silphium
      perfoliatum contained various TI with M(r) ranging from 1500 to 14,750, with some
      also containing SI. H. annuus seeds contain a unique cyclic TI of M(r) 1514 and
      similar TI were also present in other Helianthus spp. and the related species
      Tithonia diversifolia. Zinnia elegans contained a TI with M(r) 11,350 which
      appeared to represent a novel type of inhibitor distantly related to the cereal
      subgroup of Bowman-Birk inhibitors. TI and T/SI varied widely in H. annuus lines
      and wild Helianthus species in their presence or absence and composition. Similar
      T/SI components were found in the cultivated diploid H. annuus and annual diploid
      species with the B genome but not in perennials with the A genome. Some T/SI, SI
      and TI were detected in vegetative organs of sunflower and other Compositae.
      Studies of the polymorphism and distribution of proteinase inhibitors are
      relevant to the evolution of protective protein systems and the mechanisms of
      resistance to pathogenic organisms in the Compositae and other plants.

PMID- 11830137
TI  - Chemosystematic investigations of irregular diterpenes in Anisotome and related
      New Zealand Apiaceae.
AB  - A chemosystematic HPLC-UV and HPLC-MS investigation of New Zealand members of the
      Apiaceae was performed. Diterpenes were identified and quantified in methanolic
      extracts from subaerial parts of 28 taxa and 54 samples of Aciphylla, Anisotome,
      Apium, Gingidia, Lignocarpa, Oreomyrrhis, and Scandia. Six diterpenes (1-2, 4-7)
      and four polyacetylenes (8-11) were identified. The known compounds were the
      diterpenes anisotomenoic acid 1, anisotomene-1-ol 2, 16-acetoxyanisotomenoic acid
      4 and anisotomene-1,12-diol 5; and the polyacetylenes falcarinol 8, falcarindiol
      9, (+)-9(Z),17-octadecadiene-12,14-diyne-1,11,16-triol 10, and (+)-9(Z),17
      octadecadiene-12,14-diyne-1,11,16-triol 1-acetate 11. New irregular diterpenes
      13,14-dihydroanisotom-12E-ene-1,14-diol 6 and 14-methoxy-13,14-dihydroanisotom
      12E-ene-1-ol 7 were isolated from A. haastii. Isomers of the new semi-synthetic
      diterpene 16-hydroxyanisotomenoic acid 3 were detected in extracts of Anisitone
      flexuosa. Structure elucidation was performed by HR mass spectrometry and 1D and
      2D NMR spectroscopy. In crude extracts, compounds were identified by their HPLC
      retention times and their on-line HPLC-UV and MS spectra. Anisotomene diterpenes
      occurred in eight out of 16 species of the genus Anisotome, but were not detected
      in any of the other genera. In contrast, polyacetylenes were present in all the
      genera investigated.

PMID- 11830138
TI  - Essential fatty acids and phenolic acids from extracts and leachates of southern
      cattail (Typha domingensis P.).
AB  - We have been able to isolate several phytotoxic compounds from aqueous extracts
      and leachates of cattails (Typha domingensis) using activated charcoal as an
      absorbant, followed by successive extraction with organic solvents, analysis by
      GC/MS, and structural elucidation by NMR spectroscopy when possible. The
      phytotoxins were identified as essential fatty acids (linoleic acid and alpha
      linolenic acid) and phenolic compounds of known phytotoxic activity (caffeic acid
      from the aqueous extracts; caffeic, p-coumaric, and gallic acid from the
      leachates). Both extracts and the phytotoxins in the extracts have the potential
      of inhibiting the growth and chlorophyll production of several ecologically
      relevant species.

PMID- 11830139
TI  - Phytotoxicity and mammalian cytotoxicity of macrocyclic trichothecene mycotoxins
      from Myrothecium verrucaria.
AB  - Macrocyclic trichothecene toxins produced by Myrothecium verrucaria (a
      phytopathogen of interest in biological weed control) and the non-trichothecene
      toxin atranone B from Stachybotiys atra were tested for phytotoxicity in duckweed
      (Lemna pausicostata L.) plantlet cultures and kudzu (Pueraria lobata L.) leaf
      disc assays, and for mammalian cytotoxicity in four cultured cell lines. Roridin
      E and H, epi-isororidin E, and verrucarin A and J were phytotoxic (half-maximal
      effect in the concentration range 0.1-9.7 microM on duckweed and 1.5->80 microM
      on kudzu) and cytotoxic to mammalian cell lines (half-maximal inhibition of
      proliferation in the concentration range 1-35 nM). Trichoverrins A and B and
      atranone B were moderately phytotoxic (half-maximal effect in the concentration
      range 1 9-69 microM on duckweed and 13->80 microM on kudzu) and weakly cytotoxic
      with mammalian cell lines (half-maximal inhibition of proliferation in the
      concentration range 0.3->2 microM).

PMID- 11830140
TI  - Production of bioactive triterpenes by Eriobotrya japonica calli.
AB  - Callus tissue cultures induced from an axenic leaf of Eriobotrya japonica
      (Rosaceae) produced triterpenes in large amounts (ca. 50 mg/g dry wt). Nine
      triterpenes were characterized as ursolic acid, oleanolic acid, 2alpha
      hydoxyursolic acid, maslinic acid, tormentic acid, 2alpha, 19alpha-dihydroxy-3
      oxo-urs-12-en-28-oic acid, hyptadienic acid and a mixture of 3-O-cis-p
      coumaroyltormentic acid and 3-O-trans-p-coumaroyltormentic acid. The triterpene
      composition in the callus tissues was noticeably different from that in intact
      leaves. The contents of tormentic acid with antidiabetic action, and 2alpha,
      19alpha-dihydroxy-3-oxo-urs-12-en-28-oic acid with anti-HIV activity, were much
      larger than those in the intact leaves. All of the triterpenes isolated from the
      callus tissues showed an inhibitory effect comparable to (-)-epigallocatechin
      gallate (EGCG) of green tea on the activation of Epstein-Barr virus early antigen
      (EBV-EA) induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). 2alpha, 19alpha
      Dihydroxy-3-oxo-urs-12-en-28-oic acid was the most potent inhibitor among them
      and caused a significant delay of two-stage carcinogenesis on mouse skin.

PMID- 11830141
TI  - Natural anti-HIV agents-part I: (+)-demethoxyepiexcelsin and verticillatol from
      Litsea verticillata.
AB  - The eudesmane sesquiterpenoid, verticillatol (1), as well as the lignan, (+)-5'
      demethoxyepiexcelsin (2), and a known lignan, (+)-epiexcelsin (3), were isolated
      from Litsea verticillata Hance. Lignan 2 showed moderate anti-HIV activity with
      an IC(50) value of 16.4 microg/ml (42.7 microM), while the known lignan 3 was
      inactive up to a concentration of 20 microg/ml (48.3 microM). Compound 1
      demonstrated weak activity with an IC(50) value of 34.5 microg/ml (144.7 microM)
      while being devoid of cytotoxicity at 20 microg/ml. The structures were
      elucidated by 1D and 2D NMR spectroscopy, and the absolute configuration of the
      new sesquiterpenoid was determined by the generation of Mosher esters.

PMID- 11830142
TI  - Macrocyclic diterpenes from Euphorbia nivulia.
AB  - The latex of Euphorbia nivulia afforded two ingol diterpenes 3,12-diacetyl-8
      benzoylingol (4) and 3,12-diacetyl-7-benzoyl-8-nicotinylingol (5) along with
      three known ingol diterpenes 1, 2,and 3, and two known triterpenes cycloart-25-en
      3beta-ol and cyclonivulinol. Their structures have been assigned on the basis of
      their structural data as well as their acetylated products. The diterpenes 1-5
      were tested for the LPS induced PGE(2) inhibition activity.

PMID- 11830144
TI  - The structure of the major anthocyanin in Arabidopsis thaliana.
AB  - The major anthocyanin in the leaves and stems of Arabidopsis thaliana has been
      isolated and shown to be cyanidin 3-O-[2-O(2-O-(sinapoyl)-beta-D-xylopyranosyl)-6
      O-(4-O-(beta-D-glucopyranosyl)-p-coumaroyl-beta-D-glucopyranoside] 5-O-[6-O
      (malonyl) beta-D-glucopyranoside]. This anthocyanin is a glucosylated version of
      one of the anthocyanins found in the flowers of the closely related Matthiola
      incana.

PMID- 11830143
TI  - Three isoflav-3-enes and a 2-arylbenzofuran from the root bark of Erythrina
      burttii.
AB  - From the root bark of Erythrina burttii three isoflav-3-enes, 7,4'-dihydroxy-2'
      methoxy-6-(1",1"-dimethylallyl)isoflav-3-ene (trivial name, burttinol-A), 4'
      hydroxy-2'-methoxy-2",2"-dimethylpyrano[5",6":8,7]isoflav-3-ene (trivial name,
      burttinol-B), 7,4'-dihydroxy-2'-methoxy-8-(3",3"-dimethylallyl)isoflav-3-ene
      (trivial name, burttinol-C), and 2-arylbenzofuran, 6,4'-dihydroxy-2'-methoxy-5
      (1",1"-dimethylallyl)-2-arylbenzofuran (trivial name, burttinol-D) were isolated.
      In addition, the known compounds, abyssinone V-4'-methyl ether, bidwillol A,
      calopocarpin, erybraedin A, erythrabyssin II, isobavachalcone, phaseollidin and
      phaseollin were identified. The structures were determined on the basis of
      spectroscopic evidence.

PMID- 11830145
TI  - Metabolic profiling of saponins in Medicago sativa and Medicago truncatula using
      HPLC coupled to an electrospray ion-trap mass spectrometer.
AB  - Triterpene saponins isolated from Medicago sativa (alfalfa) and Medicago
      truncatula roots were separated, profiled and identified using an optimized,
      reversed-phase HPLC with on-line photodiode array detection and electrospray
      ionization mass spectrometry method (HPLC/PDA/ESI/MS). ESI source polarity and
      solvent conditions were compared. The effects of these parameters on mass
      spectral attributes were determined. Ion structures were confirmed using tandem
      mass spectrometry (MS/MS). Fifteen saponins were identified in alfalfa (cultivars
      Apollo, Radius, and Kleszczewska) based upon negative-ion HPLC/PDA/ESI/MS,
      HPLC/PDA/ESI/MS/MS and literature data. In addition, the identification of two
      new malonated saponins in alfalfa are proposed. Negative-ion HPLC/PDA/ESI/MS and
      HPLC/PDA/ESI/MS/MS spectra were utilized along with HPLC retention times to
      profile and identify 27 saponins in M. truncatula (cultivar Jemalong, A17). M.
      truncatula yielded a much more complex mixture of saponins than observed for
      alfalfa. The authors are not aware of any previous reports identifying saponin
      glycosides in M. truncatula.

PMID- 11830149
TI  - Rebaudioside F, a diterpene glycoside from Stevia rebaudiana.
AB  - The sweet diterpenoid glycoside, rebaudioside F, was isolated from leaves of a
      high rebaudioside C producing line of Stevia rebaudiana, and its structure was
      established by chemical and spectral studies.

PMID- 11830150
TI  - Vernoguinosterol and vernoguinoside, trypanocidal stigmastane derivatives from
      Vernonia guineensis (Asteraceae).
AB  - Two bitter stigmastane derivatives, vernoguinosterol (1) and vernoguinoside (2),
      have been isolated from the stem bark of Vernonia guineensis and their structures
      eludicated using spectroscopic methods. The new compounds exhibit trypanocidal
      activity.

PMID- 11830151
TI  - Structure of a geranyl-alpha-pyrone from Mimulus aurantiacus leaf resin.
AB  - A previously reported but misidentified geranyl-alpha-pyrone, in addition to six
      known compounds, was isolated from the leaf resin of Mimulus aurantiacus. HMBC
      NMR analyses of the geranyl-alpha-pyrone resolved uncertainties in the site of
      attachment of the two side chains and necessitated a revision of the previously
      reported structure. This compound is shown to be 3-geranyl-4-hydroxy-6-(2
      hydroxypropyl)-2-pyrone.

PMID- 11830152
TI  - nor-Oleanene type triterpene glycosides from the leaves of Acanthopanax
      japonicus.
AB  - Three new (1-3) and two known (4-5) triterpene glycosides were isolated from the
      leaves of Acanthopanax japonicus (Araliaceae) and elucidated structurally by
      mass, 1D, and 2D NMR spectroscopy. All the compounds possessed a nor-oleanene
      triterpene skeleton as the aglycone. The structures of 1-5 were established as 28
      O-alpha-L-rhamno-pyranosyl-(1-->4)-beta-D-glucopyranosyl-(1-->6)-beta-D
      glucopyranosyl ester of 3beta-hydroxy- 30-nor-olean-12,20(29)-diene-23,28-dioic
      acid, designated as acanjaposide A, 3beta- hydroxy-23-oxo-30-nor-olean-12,20(29)
      diene-28-oic acid, named acanjaposide B, 3beta,20alpha-dihydroxy-23-oxo-30-nor
      olean-12-en-28-oic acid, named acanjaposide C, and nipponoside E, a known
      saponin, respectively.

PMID- 11830153
TI  - Abietane diterpenoids from suspension cultured cells of Torreya nucifera var.
      radicans.
AB  - Three abietane diterpenoids were isolated from the suspension cultured cells of
      Torreya nucifera var. radicans along with four known abietane diterpenoids. Based
      on spectroscopic evidence, the structures of the three were elucidated as
      (3S,5R,10S)-7-oxo-12-methoxyabieta-8,11,13-triene-3,11-diol, (3S,5R,10S)-7-oxo-12
      methoxyabieta-8,11,13-triene-3,11,14-triol and (5R,10S)-3-oxo-7R,12
      dimethoxyabieta-8,11,13-trien-11-ol, respectively.

PMID- 11830154
TI  - Volatile oil comparison of cotyledon leaves of chemotypes of Melaleuca
      alternifolia.
AB  - Oil quantity and quality were measured for the cotyledon leaves of the commercial
      terpinen-4-ol chemical variety of Melaleuca alternifolia. Oil yield obtained by
      ethanolic extraction was 3.8 micrograms per leaf or 2.6% (dry weight basis). The
      major components of the oil were alpha-pinene (7.4%), beta-pinene (12.0%) and
      terpinolene (27.3%). The non-commercial terpinolene chemical variety was found to
      be rich in 1,8-cineole (12.5%) and terpinolene (25.4%). The non-commercial 1,8
      cineole chemical variety was rich in 1,8-cineole (37%) with significant
      quantities of alpha-pinene (15.5%), beta-pinene (23.3%) and terpinolene (10.9%).
      The cotyledon leaf composition, when compared with that of mature leaf from the
      same chemical variety, was found to be biased toward pinene and terpinolene
      biogenetic pathway constituents and hence not a good indicator of mature tree
      quality especially for the commercial terpinen-4-ol chemical variety. The
      implications of these analyses for the determination of M. alternifolia
      plantation quality and the understanding of oil formation, are discussed.

PMID- 11830155
TI  - Polyprenylated phloroglucinol derivatives from Hypericum erectum.
AB  - Three polyprenylated phloroglucinol derivatives, namely erectquione A, B, and C,
      were isolated from Hypericum erectum. Their structures were established using
      extensive spectral methods.

PMID- 11830156
TI  - Two octanordammarane triterpenes from Commiphora kua.
AB  - The resin of Commiphora kwo yielded two new octanordammarane triterpenes namely
      15 alpha-hydroxymansumbinone and 28-acetoxy-15 alpha-hydroxymansumbinone, along
      with the four known compounds, mansumbinone, mansumbinol, (16S, 20R)
      dihydroxydammar-24-en-3-one and T-cadinol. These structures were elucidated by
      spectroscopic techniques, including 1D and 2D NMR spectroscopy, and X-ray
      analysis.

PMID- 11830157
TI  - Furanoterpenoids from Siphonochilus aethiopicus.
AB  - Two new furanoterpenoid derivatives, namely 4a alpha H-3,5 alpha,8 alpha beta
      trimethyl-4,4a,9-tetrahydro-naphtho[2,3-b]-furan-8-one and 2-hydroxy-4a alpha H
      3,5 alpha, 8a beta-trimethyl-4,4a,9-tetrahydronaphtho[2,3-b]-furan-8-one, were
      isolated from Siphonochilus aethiopicus, a member of the family Zingiberaceae.
      Their structures were elucidated using high field NMR techniques.

PMID- 11830158
TI  - neo-Clerodane diterpenoids from Teucrium oliverianum and structure revision of
      teucrolin E.
AB  - The aerial parts of Teucrium oliverianum yielded two neo-clerodane diterpenoids,
      teucrolin F and G, together with the known teucrolin E. The previously proposed
      structure for teucrolin E was revised so that it contains a tetrahydrofuran ring
      instead of an oxetane ring. This was based on analysis of the NMR spectroscopic
      data of its diacetate, including its NOE spectra. In addition, the structural
      assignments of the new diterpenoids were based on 1H and 13C NMR spectroscopic
      studies, mainly 2D NMR experiments, including homonuclear and heteronuclear
      correlations.

PMID- 11830159
TI  - An isoflavanoid-neoflavonoid and an O-methylated isoflavone from the heartwood of
      Dalbergia nitidula.
AB  - An isoflavanoid (6-->2) neoflavonoid dimer and a 4',5',7-trihydroxy-2'
      methoxyisoflavone, both as the acetate derivatives were isolated from the
      heartwood of Dalbergia nitidula. Their structures were established by
      spectroscopic methods.

PMID- 11830160
TI  - O-Galloyl-C-glycosylflavones from Pelargonium reniforme.
AB  - The unique series of C-2''-acylated C-glycosylflavones is extended by the
      discovery of the C-8-glucosyl derivatives 2''-O-galloylvitexin and 2''-O
      galloylorientin and their C-6 analogues 2''-O-galloylisovitexin and 2''-O
      galloylisoorientin, representing the first described O-galloyl-C
      glycosylflavones. They are accompanied in the aerial parts of Pelargonium
      reniforme by the known non-galloylated parent analogues vitexin, orientin,
      isovitexin and isoorientin, as well as several known flavonoid-O-glycosides. The
      structures of these compounds were established from spectroscopic studies.
      Differentiation between C-glycosylation at C-6 and C-8 is discussed on the basis
      of the effects of dynamic rotational isomerism.

PMID- 11830161
TI  - Oxanthrone esters from the roots of Cassia kleinii.
AB  - From the roots of Cassia kleinii two new oxanthrone esters, kleinioxanthrone-3
      and kleinioxanthrone-4 have been isolated. Their structures were established as
      1,8-dihydroxy-3-methyl-9(10H)-anthracenone-10-oxyhexadecanoate 3 and 2,6,7
      trihydroxy-1,8-dimethoxy-3-methyl-9(10H)-anthracenone-10-oxydecanoate 4
      respectively based on degradative and spectroscopic evidence.

PMID- 11830163
TI  - Triflavonoids of Ochna calodendron.
AB  - Phytochemical investigation of the dichloromethane extract of Ochna calodendron
      leaves resulted in the isolation and identification of three known isoflavones,
      irilone, 3'-methoxyirilone and prunetin, one cyanoglucoside, menisdaurin, in
      addition to two new triflavonoid constituents, namely caloflavans A and B. The
      structures of the new compounds were established by spectroscopic methods (EI-MS,
      FAB-MS, 1H NMR, 13C NMR, HMBC and HMQC).

PMID- 11830162
TI  - Kavalactones from Piper methysticum, and their 13C NMR spectroscopic analyses.
AB  - The kavalactone, 11-methoxy-5,6-dihydroyangonin, and eight previously reported
      analogs along with four other aromatic compounds were isolated from the root
      extracts of Piper methysticum (Kava Kava). Their structural elucidations were
      made by 1H and 13C NMR spectroscopic assignments using COSY, HMBC and HMQC
      experiments.

PMID- 11830164
TI  - Hydroxyester disaccharides from fruits of cape gooseberry (Physalis peruviana).
AB  - The 3-O-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranoside of ethyl 3
      hydroxyoctanoate and the diastereomeric 3-O-alpha-L-arabinopyranosyl-(1-->6)-beta
      D-glucopyranosides of (3R) and (3S)-butyl 3-hydroxybutanoate, respectively, were
      isolated by chromatographic methods from fruits of cape gooseberry (Physalis
      peruviana) harvested in Colombia. Their structures were identified by ESI-MS/MS
      and NMR spectroscopy. The three glycoconjugates can be considered as immediate
      precursors of ethyl 3-hydroxyoctanoate and butyl 3-hydroxybutanoate, which are
      important aroma volatiles found in the fruit.

PMID- 11830165
TI  - Coumarin glucosides from Cruciata taurica.
AB  - Two new coumarin glycosides (1 and 2) along with two known coumarin glucosides,
      daphnin (3) and daphnetin glucoside (4) were isolated from the aerial parts of
      Cruciata taurica. The structures of the new compounds were elucidated by spectral
      methods and chemical means as 7-O-(6' -acetoxy-beta-D-glucopyranosyl)-8
      hydroxycoumarin (1) and 7-O-[6 '-O-(3'',4''-dihydroxycinnamoyl)-beta-D
      glucopyranosyl]-8-hydroxycoumarin (2). The phylogenetic significance of coumarins
      in C. taurica was discussed.

PMID- 11830168
TI  - Nigrumin-5-p-coumarate and nigrumin-5-ferulate, two unusual nitrile-containing
      metabolites from black currant (Ribes nigrum) seed.
AB  - Two novel nitrile-containing compounds, nigrumin-5-p-coumarate and nigrumin-5
      ferulate, together with six known flavonoids, were isolated from the seed of
      black currant (Ribes nigrum). The chemical structures of nigrumin-5-p-coumarate
      and 5-ferulate were elucidated using NMR spectroscopy as 2-trans-p
      coumaroyloxymethyl-4-beta-D-glucopyranosyloxy-2(E)-butenenitrile and 2-trans
      feruloyloxymethyl-4-beta-D-glucopyranosyloxy-2(E)-butenenitrile, respectively.

PMID- 11830167
TI  - Antiviral isoflavonoid sulfate and steroidal glycosides from the fruits of
      Solanum torvum.
AB  - The C-4 sulfated isoflavonoid, torvanol A (1), and the steroidal glycoside,
      torvoside H (3), together with the known glycoside, torvoside A (2), were
      isolated from a MeOH extract of Solanum torvum fruits. Upon enzymatic hydrolysis
      with beta-glucosidase, torvoside A (2) and torvoside H (3) yielded the
      corresponding acetal derivatives 4 and 5, respectively. Torvanol A (1), torvoside
      H (3) and compound 5 exhibited antiviral activity (herpes simplex virus type 1)
      with IC(50) values of 9.6, 23.2 and 17.4 microg/ml, respectively. Compounds 1-5
      showed no cytotoxicity (at 50 microg/ml) against BC, KB and Vero cell lines.

PMID- 11830166
TI  - (6S)-Hydroxy-3-oxo-alpha-ionol glucosides from Capparis spinosa fruits.
AB  - Two new (6S)-hydroxy-3-oxo-alpha-ionol glucosides, together with corchoionoside C
      ((6S,9S)-roseoside) and a prenyl glucoside, were isolated from mature fruits of
      Capparis spinosa. The structures were established on the basis of spectroscopic,
      chiroptic and chemical evidence. In addition, the 13C-resonance of C-9 was found
      to be of particular diagnostic value in assigning the absolute configuration at
      that center in ionol glycosides. The alpha-ionol derivatives are metabolites of
      (+)-(S)-abscisic acid.

PMID- 11830171
TI  - Comparison of the distribution of calcium-binding proteins and intrinsic
      connectivity in the lateral nucleus of the rat, monkey, and human amygdala.
AB  - A large amount of anatomic, electrophysiologic, pharmacologic, and behavioral
      data published over the past decade has provided novel insight into the function
      of the amygdala in the rat. An important question remains as to how well the data
      obtained in the rat amygdala can be extrapolated to primates. To address this
      issue from a functional neuroanatomic point of view, we compared the recently
      published data on the distribution of calcium-binding proteins (parvalbumin,
      calbindin-D(28k), calretinin) and intrinsic connectivity in the rat, monkey, and
      human amygdala. The aim of our ongoing analysis is twofold: (1) to determine
      whether the nuclei with the "same name" in the three species are
      chemoarchitectonically similar and (2) to determine whether the intradivisional,
      interdivisional, and internuclear connectivity is similarly organized in the rat
      and monkey. We focused on the lateral nucleus, which is the major recipient of
      thalamic and cortical sensory information directed to the amygdala and provides
      the most widespread intraamygdaloid connections. Our analysis suggests many
      similarities in the organization of chemoarchitectonics and intrinsic
      connectivity of the different subdivisions of the lateral nucleus of the rat,
      monkey, and human amygdala. There are also dissimilarities, however, which might
      relate to differences in the function of the amygdala in rodents and primates.

PMID- 11830169
TI  - The metabolites of the mangrove fungus Verruculina enalia No. 2606 from a salt
      lake in the Bahamas.
AB  - Two metabolites enalin A (1) and B (2), together with hydroxymethyl furfural (3)
      and three cyclodipeptides (4, 5 and 6), were isolated from the mangrove fungus
      Verruculina enaria from a salt lake in the Bahamas. Their structures were
      determined by spectroscopic methods, mainly by 2D NMR spectroscopic analyses. A
      possible biosynthetic scheme to 1 and 2 is presented.

PMID- 11830172
TI  - The role of amygdala glutamate receptors in fear learning, fear-potentiated
      startle, and extinction.
AB  - Using a paradigm known as fear-potentiated startle, we have examined the
      neurobiological substrates of Pavlovian fear conditioning. In these experiments,
      rats are trained to fear an initially neutral stimulus by pairing that stimulus
      with shock. The amount of fear elicited by the stimulus [i.e., now a conditioned
      stimulus (CS)] is later assessed by presenting startle-eliciting noise bursts
      both in the presence and also the absence of the CS. After training, startle
      responses are typically greater in the presence of the CS. Findings reviewed here
      suggest that amygdala N-methyl-D-aspartate (NMDA) receptors play a key role in
      triggering the neural changes that support fear learning and also the loss of
      fear that accompanies extinction training. Amygdala (+/-)-alpha-amino-3-hydroxy-5
      methylisoxazole-4-propionic acid (AMPA) receptors also participate in fear
      learning. However, unlike NMDA receptor antagonists, AMPA receptor antagonists
      also block fear-potentiated startle when infused prior to testing. Very recent
      data indicate that glutamate metabotropic Group II receptor agonists also block
      fear learning when infused into the amygdala prior to training, and block fear
      potentiated startle when infused prior to testing. A fuller understanding of the
      role of amygdala glutamate systems in fear and fear learning may suggest novel
      pharmacological approaches to the treatment of clinical anxiety disorders.

PMID- 11830173
TI  - Expression of fear-conditioning is accompanied by increased paired-pulse
      depression within the amygdala.
AB  - Fear-conditioning is a model of fear learning and anxiety. The lateral nucleus of
      the amygdala (LA) provides a critical link for relaying thalamic and cortical
      auditory information to the rest of the amygdala during the fear conditioning
      process. Alterations in excitatory synaptic transmission in the thalamic to LA
      pyramidal cells was studied using whole-cell patch clamp recordings in brain
      slices from fear-conditioned animals. Following paired stimulation of the
      thalamic afferents, paired-pulse depression (PPD) could be recorded at 200-ms to
      2-s intervals. Increasing transmitter release by decreasing the Mg2+/Ca2+ ratio
      enhanced PPD suggesting that PPD is reflective of changes in release probability.
      Analysis of the pairs of composite, alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptor-mediated
      excitatory postsynaptic currents (EPSCs) showed that there was no correlation
      between EPSC pairs suggesting that PPD may be mediated through a release
      independent mechanism of presynaptic origin. However, AMPA and NMDA receptor
      mediated PPD had a different time course and magnitude suggesting postsynaptic
      factors may be involved in PPD. After fear-conditioning PPD of the composite and
      AMPA receptor-mediated EPSCs was enhanced suggesting that neurotransmitter
      release may be increased in learned fear. The NMDA receptor-mediated PPD was
      however not altered in fear-conditioned animals. The differences in response of
      AMPA and NMDA receptor-mediated PPD suggest that postsynaptic mechanisms may also
      be involved in the expression of fear conditioning.

PMID- 11830174
TI  - Amygdala priming results in conditioned place avoidance.
AB  - Priming involves daily stimulation of the basolateral nucleus of the amygdala
      (BLA) for 5 days using a dose of the GABA(A) receptor antagonist, bicuculline
      methiodide (BMI), that is subthreshold to generate anxiogenic-like responses. The
      coordinated physiological and behavioral response of the primed rat is similar to
      the symptoms of human panic disorder and has been used as a model to study panic
      attacks. If the priming procedure is indeed similar to human panic disorder, then
      the context in which priming occurs should become associated with aversive
      conditioning and avoidance as seen in secondary agoraphobia following panic
      attacks in humans. Therefore, the purpose of this study was to further
      characterize the behavioral response of priming using the conditioned place
      avoidance (CPA) task that utilizes distinct tactile cues of a grid floor (Grid+)
      or hole floor (Grid-). Male Wistar rats (275-300 g) were implanted bilaterally
      with guide cannulae positioned 1 mm above the BLA. Grid+ animals were placed in
      the conditioning chamber containing grid floors immediately after a 6-pmol (in
      250 nl) BMI injection into the BLA and on hole floors following a sham (250 nl
      vehicle) injection. Grid animals were placed in the chamber containing hole
      floors after the BMI injection and on grid floors following the sham injection.
      Animals were placed in the chamber for 20 min following each injection and
      injections were separated by 4 h. After 5 days of this treatment, the animals
      were primed. Two days later, during avoidance testing, each animal was placed in
      the chamber containing both floors for 30 min. Priming with daily 6-pmol BMI
      injections into the BLA results in CPA or an aversion to the floor paired with
      the BMI injection. These results suggest that priming may result in phobic-like
      responses, similar to the avoidance behavior exhibited by panic disorder
      patients.

PMID- 11830175
TI  - Behavioral reactivity to stress: amplification of stress-induced noradrenergic
      activation elicits a galanin-mediated anxiolytic effect in central amygdala.
AB  - Brain norepinephrine (NE) modulates many aspects of the stress response. The
      interaction between NE and neuropeptides such as galanin, with which it is
      closely associated and which may be released from noradrenergic terminals under
      conditions of high activity, has not been well studied. We therefore investigated
      the modulatory effects of galanin in the central nucleus of the amygdala (CeA) on
      behavioral responsivity to stress when activation of the noradrenergic system was
      amplified using the adrenergic autoreceptor antagonist yohimbine (2.5 mg/kg ip).
      Either immobilization stress or yohimbine alone had anxiogenic effects on rat
      behavior in the elevated plus maze. However, yohimbine pretreatment before stress
      produced a paradoxical anxiolytic response, which we hypothesized was
      attributable to galanin release in CeA. Microdialysis verified that yohimbine
      amplified NE release in CeA during immobilization stress, and also showed that
      whereas there was no detectable change in galanin release in CeA during stress
      alone, there was an increase during immobilization stress after yohimbine
      pretreatment. Bilateral administration of the galanin antagonist M40 into CeA
      before stress blocked the anxiolytic influence of yohimbine pretreatment.
      Exogenous galanin mimicked the anxiolytic effect of yohimbine pretreatment, and
      this too was blocked by M40. These results suggest that amplifying the
      noradrenergic response to stress can recruit galanin release in CeA, which
      buffers the anxiety-like behavioral response to acute stress. The balance between
      noradrenergic and peptidergic neurotransmission may be modified by prior stress,
      drug treatment or genetic variability, and may represent a novel target for
      treatment of stress-related neuropsychiatric disorders.

PMID- 11830176
TI  - Neuropeptide Y-Y2 receptors mediate anxiety in the amygdala.
AB  - The behavioral effects of direct injection of the neuropeptide Y (NPY) Y2
      receptor agonist C2-NPY into the basolateral nucleus of the amygdala (BLA) was
      assessed in rats utilizing the social interaction test (SI). C2-NPY decreased SI
      time in a dose-dependent manner with a significant change observed at a dose of
      80 pmol/100 nl. The anxiogenic effects produced by intra-amygdalar C2-NPY
      injections were reversed with intraperitoneal administration of alprazolam (1
      mg/kg), a known anxiolytic. These findings support the hypothesis that Y2
      receptors are involved in the regulation of the anxiety response.

PMID- 11830177
TI  - Leptin suppression of hypothalamic NPY expression and feeding, but not amygdala
      NPY expression and experimental anxiety.
AB  - Leptin decreases food intake through actions in the hypothalamus, partly through
      interactions with neuropeptide Y (NPY). However, NPY also produces behavioral
      antistress effects mediated inter alia through the amygdala. If leptin generally
      suppresses NPY function, the utility of leptin-mimics for treatment of obesity
      might be limited. Here, we therefore compared the effects of
      intracerebroventricular leptin on hypothalamic and amygdala NPY expression, as
      well as the respective related behaviors, i.e., feeding and experimental anxiety.
      Rats were injected intracerebroventricularly with leptin once daily for 6 days.
      Leptin-treated subjects consumed significantly less chow and had reduced body
      weight at the end of the treatment period compared to saline-treated controls.
      This was accompanied by a significant suppression of hypothalamic NPY expression.
      In contrast, the expression of NPY within the amygdala was unaffected by leptin.
      In parallel, in an established animal model of anxiety, the elevated plus-maze,
      no effect of leptin on anxiety-related behaviors was observed. In conclusion,
      leptin selectively affects the hypothalamic NPY system and its functional
      outflow, i.e., feeding and endocrine stress responses. Despite modifying
      endocrine responses, leptin treatment does not affect behavioral measures of
      experimental anxiety.

PMID- 11830178
TI  - Glucose metabolism in the amygdala in depression: relationship to diagnostic
      subtype and plasma cortisol levels.
AB  - In a previous positron emission tomography (PET) study of major depression, we
      demonstrated that cerebral blood flow was increased in the left amygdala in
      unipolar depressives with familial pure depressive disease (FPDD) relative to
      healthy controls [J. Neurosci. 12 (1992) 3628.]. These measures were obtained
      from relatively low-resolution PET images using a stereotaxic method based upon
      skull X-ray landmarks. The current experiments aimed to replicate and extend
      these results using higher-resolution glucose metabolism images and magnetic
      resonance imaging (MRI)-based region-of-interest (ROI) analysis. The specificity
      of this finding to FPDD was also investigated by assessing depressed samples with
      bipolar disorder (BD-D) and depression spectrum disease (DSD). Finally, the
      relationship between amygdala metabolism and plasma cortisol levels obtained
      during the scanning procedure was assessed. Glucose metabolism was measured using
      PET and 18F-fluorodeoxyglucose (18FDG) in healthy control (n=12), FPDD (n=12),
      DSD (n=9) and BD-D (n=7) samples in the amygdala and the adjacent hippocampus.
      The left amygdala metabolism differed across groups (P<.001), being increased in
      both the FPDD and BD-D groups relative to the control group. The left amygdala
      metabolism was positively correlated with stressed plasma cortisol levels in both
      the unipolar (r=.69; P<.005) and the bipolar depressives (r=0.68;.1<P<.05). In
      contrast, neither significant main effects of diagnosis nor significant
      relationships with plasma cortisol were evident in post hoc analyses of
      metabolism in the right amygdala or the hippocampus. Preliminary assessment of BD
      subjects imaged during remission suggested that amygdala metabolism is also
      elevated in remitted subjects who are not taking mood-stabilizing drugs, but
      within the normal range in subjects taking mood stabilizers. These data confirm
      our previous finding that neurophysiological activity is abnormally increased in
      FPDD, and extend it to BD-D. These abnormalities were not accounted for by
      spilling in of radioactivity from the adjacent hippocampus. The correlation
      between left amygdala metabolism and stressed plasma cortisol levels may
      conceivably reflect either the effect of amygdala activity on corticotropin
      releasing hormone (CRH) secretion or the effect of cortisol on amygdala function.

PMID- 11830179
TI  - The amygdala and related structures in the pathophysiology of autism.
AB  - Autism is a neurodevelopmental disorder that is defined behaviorally by severe
      deficiencies in reciprocal social interaction, verbal and nonverbal
      communication, and restricted interests. The amygdala is involved in the
      regulation of social behaviors and may be an important site of pathology for the
      social dysfunction seen in autism. This review focuses on lesion, postmortem, and
      neuroimaging studies that investigate the amygdala and related structures in this
      disorder. Other brain regions potentially involved in the neuropathology of
      autism are also briefly discussed. Although supportive evidence exists for
      amygdala dysfunction in autism, the currently available data are inconsistent and
      additional research is needed.

PMID- 11830180
TI  - Local circuit regulation of paraventricular nucleus stress integration: glutamate
      GABA connections.
AB  - Limbic neurocircuits play a central role in regulation of the hypothalamic
      pituitary-adrenocortical (HPA) axis. Limbic influences on adrenocortical hormone
      secretion are mediated by transynaptic activation or inhibition of
      hypophysiotrophic neurons in the medial parvocellular paraventricular nucleus
      (PVN). Projections from the ventral subiculum, prefrontal cortex, medial
      amygdala, lateral septum, paraventricular thalamus and suprachiasmatic nucleus
      (SN) terminate in the immediate surround of the PVN, an area heavily populated by
      GABAergic interneurons. As such, these regions are positioned to modulate
      paraventricular output via excitation or inhibition of interneuronal projections
      into the PVN. In addition, the same limbic and diencephalic regions have
      projections to local PVN-projecting hypothalamic and basal telencephalic nuclei,
      including the dorsomedial and medial preoptic nuclei and the bed nucleus of the
      stria terminalis. These regions are involved in both inhibitory and excitatory
      regulation of the stress axis, indicating that they contain heterogeneous
      neuronal populations whose relative impact on the PVN is determined by the nature
      of afferent stimuli. Thus, limbic modulation of the pituitary-adrenocortical
      system appears to be a multisynaptic process integrated at the level of local PVN
      projecting neurocircuits. Local circuits are likely the primary integrators of
      anticipatory stress responses, and may indeed be the focus of HPA dysfunction
      seen with aging or affective disease.

PMID- 11830181
TI  - The dorsomedial hypothalamus and the response to stress: part renaissance, part
      revolution.
AB  - Emotional stress provokes a stereotyped pattern of autonomic and endocrine
      changes that is highly conserved across diverse mammalian species. Nearly 50
      years ago, a specific region of the hypothalamus, the hypothalamic defense area,
      was defined by the discovery that electrical stimulation in this area evoked
      changes that replicated this pattern. Attention later shifted to the hypothalamic
      paraventricular nucleus (PVN) owing to (1) elucidation of its role as the final
      common pathway mediating activation of the hypothalamic-pituitary-adrenal (HPA)
      axis, a defining feature of the stress response and (2) the finding that the PVN
      was the principal location of hypothalamic neurons that project directly to
      spinal autonomic regions. Consequently, a primary role for the PVN as the
      hypothalamic center integrating the autonomic and endocrine response to stress
      was inferred. However, our findings indicate that neurons in the nearby
      dorsomedial hypothalamus (DMH)--a region originally included in the hypothalamic
      defense area--and not in the PVN play a key role in the cardiovascular changes
      associated with emotional or exteroceptive stress. Indeed, excitation of neurons
      in the parvocellular PVN and consequent recruitment of the HPA axis that occurs
      in exteroceptive stress is also signaled from the DMH. Thus, the DMH may
      represent a higher order hypothalamic center responsible for integrating
      autonomic, endocrine and even behavioral responses to emotional stress.

PMID- 11830182
TI  - The medial hypothalamic defensive system: hodological organization and functional
      implications.
AB  - The hypothalamus is a relatively small division of the vertebrate forebrain that
      plays especially important roles in neural mechanisms assuring homeostasis,
      defense, and reproduction. Previous studies from our laboratory have suggested a
      distinct circuit in the medial hypothalamic zone as critically involved in the
      organization of innate defensive behavior. Thus, after exposure to a natural
      predator known to elicit innate defensive responses, increased Fos levels in the
      medial zone of the hypothalamus have been found restricted to the anterior
      hypothalamic nucleus, dorsomedial part of the ventromedial nucleus, and dorsal
      premammillary nucleus (PMd). Previous anatomical studies have shown that these
      Fos-responsive cell groups in the medial hypothalamus are interconnected in a
      distinct neural system, in which the PMd appears to be a critical element for the
      expression of defensive responses elicited by the presence of a predator. The
      purpose of this review is to provide an overview of what is currently known about
      the functional and hodological organization of this hypothalamic circuit
      subserving defensive responses.

PMID- 11830183
TI  - Role of norepinephrine in the dorsomedial hypothalamic panic response: an in vivo
      microdialysis study.
AB  - Blockade of gamma-aminobutyric acid-A (GABA(A)) receptors in the dorsomedial
      hypothalamus (DMH) elicits a panic-like response that includes increases in heart
      rate (HR), blood pressure (BP), respiration rate (RR), and anxiety.
      Norepinephrine (NE) has been postulated to be critical in regulating panic and
      anxiety responses. Therefore, the first study sought to determine changes in
      extracellular NE levels within the DMH following acute blockade of GABA(A)
      receptors in the DMH using in vivo microdialysis. Rats were implanted with
      femoral arterial catheters and microdialysis probes into the DMH. Following
      recovery, the DMH of conscious rats were perfused with 100, 150, or 200 microM
      solutions of the GABA(A) receptor antagonist bicuculline methiodide (BMI) via the
      microdialysis probe. HR and BP responses were recorded and the changes in
      extracellular levels of NE in the dialysate samples from the DMH were determined
      by HPLC. Rats receiving BMI injections showed dose-dependent increases in both
      the extracellular NE levels in the DMH as well as HR and BP. The second study was
      conducted to test the functional importance of NE in the DMH to the BMI-induced
      physiological responses. The effects of BMI microinjection into the DMH were
      measured at baseline and 10 days after local injection of either vehicle or two
      doses of 6-hydroxydopamine (6-OHDA), a neurotoxin known to lesion NE terminals.
      There was a significant loss of tissue NE levels as well as BMI-induced HR, BP
      and RR responses in the 6-OHDA-treated but not vehicle-treated rats. Thus,
      blockade of GABA(A) receptors in the DMH results in NE release and the presence
      of NE appears to be necessary for eliciting the physiological components of the
      panic-like responses in this region.

PMID- 11830184
TI  - Both the shell of the nucleus accumbens and the central nucleus of the amygdala
      support amphetamine self-administration in rats.
AB  - Intracranial self-administration of drugs offers the opportunity to localize the
      neuronal substrates mediating the rewarding effects of drugs. The purpose of the
      present study was to explore whether the nucleus accumbens shell and the central
      nucleus of the amygdala, two components of the "extended amygdala," would support
      self-administration of the psychostimulant amphetamine. Male Wistar rats were
      trained to lever press under a Fixed Ratio 1 schedule of reinforcement for D
      amphetamine injections (0, 1.0, 1.5, 2.0 and 3.0 microg/microl/inj) into either
      the nucleus accumbens shell or the central nucleus of the amygdala. An ascending
      limb dose-response function with peak responding at the 2.0 microg/microl/inj
      dose was obtained for self-administration at both brain sites. These results
      indicate that monoaminergic transmission in both the nucleus accumbens shell and
      the central nucleus of the amygdala mediates the rewarding effects of
      amphetamine. Further, the present study provides additional evidence about the
      functional homogeneity of the forebrain continuum called the "extended amygdala."

PMID- 11830185
TI  - Central nucleus of the amygdala and the effects of alcohol and alcohol-drinking
      behavior in rodents.
AB  - This article will review key literature on the effects of alcohol on the amygdala
      and the involvement of the amygdala in regulating alcohol drinking in mice and
      rats. Special emphasis will be placed on the central nucleus of the amygdala
      (CeA) because this nucleus is a major component of the extended amygdala, which
      has been implicated in regulating alcohol-drinking behavior. Immunocytochemical
      and in situ hybridization studies indicate that acute high-dose ethanol
      administration increases c-fos expression in GABAergic neurons within the CeA of
      the rat, suggesting activation of these neurons by ethanol. A similar high-dose
      (4 g/kg ethanol) effect on c-fos expression in the CeA of C57 mice was also
      observed, whereas the DBA mice showed increased c-fos expression in the CeA in
      the dose range of 1.25-4.0 g/kg. Studies with DBA x C57 F2 intercross mice
      suggest that there may be a relationship between the neuronal activating effects
      of ethanol in the CeA and the locomotor stimulating effects of ethanol. Studies
      with rats examining the effects of acute ethanol or chronic alcohol drinking on
      local cerebral glucose utilization (LCGU) rates (as a measure of synaptic
      activity) indicated that (a) acute ethanol (0.25-2.0 g/kg) had little effect on
      LCGU rates in the CeA; (b) basal LCGU rates were reduced in the CeA as a result
      of chronic alcohol drinking; and (c) oral self-administration of ethanol
      increased LCGU values within the CeA. Microdialysis studies demonstrated that
      acute ethanol (2 g/kg) injection increased dopamine (DA) and serotonin (5-HT)
      release in the CeA. Microinjection studies indicate that GABA(A) receptors within
      the CeA are involved in oral ethanol self-administration. Overall, the findings
      from the various studies support a role for the CeA in mediating the stimulating
      actions of alcohol in mice and regulating alcohol-drinking behavior in mice and
      rats.

PMID- 11830186
TI  - Neural substrates of conditioned-cued relapse to drug-seeking behavior.
AB  - Relapse to drug use following abstinence is a significant impediment in the long
      term treatment of drug abuse and dependence. Conditioned stimuli are believed to
      be critically involved in activating drug craving and relapse to compulsive drug
      taking behavior. Studies in humans and animal models have recently begun to
      identify the fundamental neural circuitry that mediates relapse following
      withdrawal from chronic drug self-administration. The current review summarizes
      key findings in this area that have converged on the amygdalar complex and
      regions of the frontal lobe as critical structures in conditioned-cued relapse.
      It is proposed that the amygdala is a key regulator of discrete stimulus
      reinforcer associations, while the anterior cingulate and orbitofrontal cortex
      are critical regulators of relapse evoked by conditioned stimuli that predict
      drug availability. This corticolimbic circuitry may form the neural basis of
      multiple long-term conditioned associations produced by a variety of drugs of
      abuse ranging from psychostimulants to opiates. Future studies aimed at
      discerning the functional roles of these pathways will provide critical direction
      for the development of treatments for the prevention of relapse.

PMID- 11830187
TI  - Landmines and cluster bombs.

PMID- 11830188
TI  - Infant rape in South Africa.

PMID- 11830189
TI  - The ups and downs of Down's syndrome.

PMID- 11830190
TI  - Pulmonary oedema at moderately high altitudes.

PMID- 11830191
TI  - Disease severity as a predictor of outcome in scleroderma.

PMID- 11830192
TI  - Immunotherapy for psoriasis: from serendipity to selectivity.

PMID- 11830193
TI  - Alcohol consumption and risk of dementia: the Rotterdam Study.
AB  - BACKGROUND: Light-to-moderate alcohol consumption reduces the risk of coronary
      heart disease and stroke. Because vascular disease is associated with cognitive
      impairment and dementia, we hypothesised that alcohol consumption might also
      affect the risk of dementia. METHODS: We examined the relation between alcohol
      consumption and risk of dementia in individuals taking part in the Rotterdam
      Study--a prospective population-based study of 7983 individuals aged 55 years and
      older. We studied all participants who did not have dementia at baseline (1990
      93) and who had complete data on alcohol consumption (n=5395). Through follow-up
      examinations in 1993-94 and 1997-99 and an extensive monitoring system, we
      obtained nearly complete follow-up (99.7%) until the end of 1999. We used
      proportional hazards regression analysis, adjusted for age, sex, systolic blood
      pressure, education, smoking, and body-mass index, to compare the risk of
      developing dementia between individuals who regularly consumed alcohol and
      individuals who did not consume alcohol. FINDINGS: The average follow-up was 6.0
      years. During this period, 197 individuals developed dementia (146 Alzheimer's
      disease, 29 vascular dementia, 22 other dementia). The median alcohol consumption
      was 0.29 drinks per day. Light-to-moderate drinking (one to three drinks per day)
      was significantly associated with a lower risk of any dementia (hazard ratio 0.58
      [95% CI 0.38-0.90]) and vascular dementia (hazard ratio 0.29 [0.09-0.93]). We
      found no evidence that the relation between alcohol and dementia varied by type
      of alcoholic beverage. INTERPRETATION: These findings suggest that light-to
      moderate alcohol consumption is associated with a reduced risk of dementia in
      individuals aged 55 years or older. The effect seems to be unchanged by the
      source of alcohol.

PMID- 11830194
TI  - Effect of race on outcome of orthotopic liver transplantation: a cohort study.
AB  - BACKGROUND: There is significant evidence to suggest that long-term survival
      after renal transplantation is significantly lower in African Americans than in
      other races. We aimed to establish whether there was a difference in survival in
      African Americans compared with other races after orthotopic liver
      transplantation (OLT) and whether race was an independent predictor of survival.
      METHODS: We collected data from the United Network of Organ Sharing transplant
      registry for all liver transplants done between 1988 and 1996 in the USA. We also
      recorded information on age, sex, race, blood group, and cause of death for the
      donors and recipients. FINDINGS: 2-year graft survival was significantly lower
      for African Americans (601 of 884, 68%) and Asians (266 of 416, 64%) compared
      with white Americans (8703 of 11762, 74%) and Hispanics (878 of 1220, 72%). 2
      year and 5-year patient survival were significantly lower for African Americans
      (654 of 884 [74%], 270 of 565 [48%]) and Asians (287 of 416 [69%], 92 of 252
      [37%]) compared with white Americans (9786 of 11762 [83%], 4357 of 7514 [58%])
      and Hispanics (964 of 1220 [79%], 341 of 657 [52%]). Compared with white
      Americans, African American (hazard ratio 1.36, 95% CI 1.16-1.60, p<0.0001) and
      Asian (1.25, 1.01-1.56, p=0.03) race were independent predictors of poor survival
      at 2 years. INTERPRETATION: African Americans and Asians have a worse outcome
      after OLT compared with white Americans and Hispanics. The higher rate of chronic
      rejection in African Americans and a relatively worse outcome in other minority
      races merits further examination.

PMID- 11830195
TI  - Clinical picture. Metastatic calcification.

PMID- 11830196
TI  - Direct thrombin inhibitors in acute coronary syndromes: principal results of a
      meta-analysis based on individual patients' data.
AB  - BACKGROUND: To obtain more reliable and precise estimates of the effect of direct
      thrombin inhibitors in the management of acute coronary syndromes, including
      patients undergoing percutaneous coronary intervention, we undertook a meta
      analysis based on individual patients' data from randomised trials comparing a
      direct thrombin inhibitor (hirudin, bivalirudin, argatroban, efegatran, or
      inogatran) with heparin. METHODS: We included trials that involved at least 200
      patients. The primary efficacy outcome was death or myocardial infarction, and
      the primary safety outcome was major bleeding. Data from individual trials were
      combined by use of a modified Mantel-Haenszel method. FINDINGS: In 11 randomised
      trials, 35,970 patients were assigned up to 7 days' treatment with a direct
      thrombin inhibitor or heparin and followed up for at least 30 days. Compared with
      heparin, direct thrombin inhibitors were associated with a lower risk of death or
      myocardial infarction at the end of treatment (4.3% vs 5.1%; odds ratio 0.85 [95%
      CI 0.77-0.94]; p=0.001) and at 30 days (7.4% vs 8.2%; 0.91 [0.84-0.99]; p=0.02).
      This was due primarily to a reduction in myocardial infarctions (2.8% vs 3.5%;
      0.80 [0.71-0.90]; p<0.001) with no apparent effect on deaths (1.9% vs 2.0%; 0.97
      [0.83-1.13]; p=0.69). Subgroup analyses suggested a benefit of direct thrombin
      inhibitors on death or myocardial infarction in trials of both acute coronary
      syndromes and percutaneous coronary interventions. A reduction in death or
      myocardial infarction was seen with hirudin and bivalirudin but not with
      univalent agents. Compared with heparin, there was an increased risk of major
      bleeding with hirudin, but a reduction with bivalirudin. There was no excess in
      intracranial haemorrhage with direct thrombin inhibitors. INTERPRETATION: Direct
      thrombin inhibitors are superior to heparin for the prevention of death or
      myocardial infarction in patients with acute coronary syndromes. This information
      should prompt further clinical development of direct thrombin inhibitors for the
      management of arterial thrombosis.

PMID- 11830197
TI  - Pulmonary extravascular fluid accumulation in recreational climbers: a
      prospective study.
AB  - BACKGROUND: High altitude pulmonary oedema (HAPE) that is severe enough to
      require urgent medical care is infrequent. We hypothesised that subclinical HAPE
      is far more frequent than suspected during even modest climbs of average effort.
      METHODS: We assessed 262 consecutive climbers of Monte Rosa (4559 m), before
      ascent and about 24 h later on the summit 1 h after arriving, by clinical
      examination, electrocardiography, oximetry, spirometry, carbon monoxide transfer,
      and closing volume. A chest radiograph was taken at altitude. FINDINGS: Only one
      climber was evacuated for HAPE, but 40 (15%) of 262 climbers had chest rales or
      interstitial oedema on radiograph after ascent. Of 37 of these climbers, 34 (92%)
      showed increased closing volume. Of the 197 climbers without oedema, 146 (74%)
      had an increase in closing volume at altitude. With no change in vital capacity,
      forced expiratory volume in 1 s and forced expiratory flow at 25-75% of forced
      vital capacity increased slightly at altitude, without evidence of oedema. If we
      assume that an increased closing volume at altitude indicates increased pulmonary
      extravascular fluid, our data suggest that three of every four healthy,
      recreational climbers have mild subclinical HAPE shortly after a modest climb.
      INTERPRETATION: The risk of HAPE might not be confined to a small group of
      genetically susceptible people, but likely exists for most climbers if the rate
      of ascent and degree of physical effort are great enough, especially if lung size
      is normal or low.

PMID- 11830198
TI  - Neuronal target genes of the neuron-restrictive silencer factor in neurospheres
      derived from fetuses with Down's syndrome: a gene expression study.
AB  - BACKGROUND: Identification of genes and characterisation of their function is an
      essential step towards understanding complex pathophysiological abnormalities in
      Down's syndrome. We did a study to investigate abnormalities in gene expression
      in human neuronal stem cells and progenitor cells from Down's syndrome and
      control post-mortem human fetal tissue. METHODS: Indexing-based differential
      display PCR was done on neuronal precursor cells derived from the cortex of a
      fetus with Down's syndrome, and findings were compared with those of two control
      samples. Findings were validated against neurosphere preparations from three
      independent Down's syndrome fetuses and five independent controls by real-time
      quantitative PCR. FINDINGS: Results of differential display PCR analysis showed
      that SCG10--a neuron--specific growth-associated protein regulated by the neuron
      restrictive silencer factor REST-was almost undetectable in the Down's syndrome
      sample. This finding was validated by real-time PCR. We also found that other
      genes regulated by the REST transcription factor were selectively repressed,
      whereas non-REST-regulated genes with similar functions were unaffected. Changes
      in expression of several key developmental genes in the Down's syndrome stem-cell
      and progenitor-cell pool correlated with striking changes in neuron morphology
      after differentiation. INTERPRETATION: Our findings suggest a link between
      dysregulation of the REST transcription factor and some of the neurological
      deficits seen in Down's syndrome. Experimental REST downregulation has been shown
      to trigger apoptosis, which could account for the striking and selective loss of
      neurons in the differentiated Down's syndrome cell preparations.

PMID- 11830199
TI  - A child with aphthae and diarrhoea.

PMID- 11830201
TI  - Rape of girls in South Africa.
AB  - Child rape violates human rights and causes immediate and long-term health
      problems for the child. In the 1998 South Africa Demographic and Health Survey,
      we assessed frequency of rape in a nationally representative study of 11735 women
      aged 15-49 years. 153 (1.6%, 95% CI 1.2-1.9%) of these women had been raped
      (forced or persuaded to have sex against their will) before the age of 15 years.
      Our results show that younger women were significantly more likely to report rape
      than older women (p<0.0001). The largest group of perpetrators (33%) were school
      teachers. Our findings suggest that child rape is becoming more common, and lend
      support to qualitative research of sexual harassment of female students in
      schools in Africa.

PMID- 11830200
TI  - Hepatocyte transplantation as a treatment for glycogen storage disease type 1a.
AB  - Treatment of many inherited disorders of hepatic metabolism is still challenging.
      Hepatocyte transplantation was done in a 47-year-old woman who had glycogen
      storage disease type 1a and severe fasting hypoglycaemia. 2 billion viable
      hepatocytes were infused via an indwelling portal-vein catheter, followed by a
      triple immunosuppression regimen with mycophenolate mofetil, tacrolimus, and
      steroids. 9 months after transplantation, on only tacrolimus, she eats a normal
      diet and can fast for 7 h without experiencing hypoglycaemia. Our results show
      that hepatocyte transplantation might be an alternative to liver transplantation
      in glycogen storage disease type 1a.

PMID- 11830202
TI  - Chromosomal congenital anomalies and residence near hazardous waste landfill
      sites.
AB  - Previous findings of the EUROHAZCON study showed a 33% increase in risk of non
      chromosomal anomalies near hazardous waste landfill sites. Here, we studied 245
      cases of chromosomal anomalies and 2412 controls who lived near 23 such sites in
      Europe. After adjustment for confounding by maternal age and socioeconomic
      status, we noted a higher risk of chromosomal anomalies in people who lived close
      to sites (0-3 km) than in those who lived further away (3-7 km; odds ratio 1.41,
      95% CI 1.00-1.99). Our results suggest an increase in risk of chromosomal
      anomalies similar to that found for non-chromosomal anomalies.

PMID- 11830203
TI  - Support rallied for reconstructing health in Afghanistan.

PMID- 11830208
TI  - Targeted treatment for incontinence beckons.

PMID- 11830209
TI  - One year after the Gujarat earthquake.

PMID- 11830210
TI  - Denmark needs more psychiatric units, say Danish psychiatrists.

PMID- 11830211
TI  - Reform in German hospital funding system concerns doctors.

PMID- 11830212
TI  - UN inspectorate gives WHO administration a mixed review.

PMID- 11830213
TI  - Cardiac surgeons in England face publication of outcomes data.

PMID- 11830214
TI  - Portuguese judge frees 15 women accused of having illegal abortions.

PMID- 11830215
TI  - Argentina appoints new health minister while health system takes the strain.

PMID- 11830216
TI  - Ulcerative colitis.
AB  - Ulcerative colitis is a chronic inflammatory disease of the rectum and colon.
      Results from many studies in people and animals of intestinal inflammation
      suggest that ulcerative colitis results from environmental factors triggering a
      loss of tolerance for normal intestinal flora in genetically susceptible
      individuals. Although progress has been made in the overall management of the
      disease, no innovative treatment has been developed. By contrast with Crohn's
      disease, there are few clinical data on biological agents. Probiotics seem the
      most promising of several experimental and traditional agents that have been
      investigated in controlled clinical trials.

PMID- 11830217
TI  - Cohort studies: marching towards outcomes.
AB  - A cohort study tracks two or more groups forward from exposure to outcome. This
      type of study can be done by going ahead in time from the present (prospective
      cohort study) or, alternatively, by going back in time to comprise the cohorts
      and following them up to the present (retrospective cohort study). A cohort study
      is the best way to identify incidence and natural history of a disease, and can
      be used to examine multiple outcomes after a single exposure. However, this type
      of study is less useful for examination of rare events or those that take a long
      time to develop. A cohort study should provide specific definitions of exposures
      and outcomes: determination of both should be as objective as possible. The
      control group (unexposed) should be similar in all important respects to the
      exposed, with the exception of not having the exposure. Observational studies,
      however, rarely achieve such a degree of similarity, so investigators need to
      measure and control for confounding factors. Reduction of loss to follow-up over
      time is a challenge, since differential losses to follow-up introduce bias.
      Variations on the cohort theme include the before-after study and nested case
      control study (within a cohort study). Strengths of a cohort study include the
      ability to calculate incidence rates, relative risks, and 95% CIs. This format is
      the preferred way of presenting study results, rather that with p values.

PMID- 11830218
TI  - The error cascade.

PMID- 11830219
TI  - Munchausen's syndrome.

PMID- 11830220
TI  - Sponsorship, authorship, and accountability.

PMID- 11830221
TI  - Sponsorship, authorship, and accountability.

PMID- 11830222
TI  - Sponsorship, authorship, and accountability.

PMID- 11830223
TI  - Sponsorship, authorship, and accountability.

PMID- 11830224
TI  - Sponsorship, authorship, and accountability.

PMID- 11830226
TI  - Patients' motivations for physician-assisted suicide.

PMID- 11830225
TI  - Biological response modifiers in rheumatoid arthritis.

PMID- 11830228
TI  - Splenic tuberculosis and HIV-1 infection.

PMID- 11830229
TI  - Invasive and medical therapy for coronary artery disease.

PMID- 11830230
TI  - Invasive and medical therapy for coronary artery disease.

PMID- 11830232
TI  - Metformin in non-alcoholic steatohepatitis.

PMID- 11830233
TI  - Invasive and medical therapy for coronary artery disease.

PMID- 11830234
TI  - Unreliable immunoassays, patients' safety, and clinical research.

PMID- 11830236
TI  - Treatment of cervical cancer.

PMID- 11830237
TI  - Treatment of cervical cancer.

PMID- 11830239
TI  - Breastfeeding and the second baby.

PMID- 11830240
TI  - Family planning in Bangladesh.

PMID- 11830241
TI  - Algorithm-based management of pneumonia in HIV-1-infected patients.

PMID- 11830242
TI  - Prescription charges for tuberculosis drugs.

PMID- 11830243
TI  - Getting science into international aid.

PMID- 11830254
TI  - The PXR crystal structure: the end of the beginning.

PMID- 11830255
TI  - CGRP receptors: a headache to study, but will antagonists prove therapeutic in
      migraine?

PMID- 11830257
TI  - The relationship between the use of a synapse and its strength.

PMID- 11830256
TI  - Chromaffin cell research in the new millennium.

PMID- 11830260
TI  - World AIDS Day commemorated.

PMID- 11830261
TI  - Are endothelium-derived hyperpolarizing and contracting factors isoprostanes?
AB  - The endothelium releases many vasoactive substances, including prostacyclin,
      nitric oxide and endothelin, in addition to several other factors about which
      little is known. The latter are referred to as 'endothelium-derived
      hyperpolarizing factors' (EDHFs) and 'endothelium-derived contracting factors'
      (EDCFs). Although there is much debate about the identities of EDHFs and EDCFs, a
      prevailing hypothesis is that they are cyclooxygenase-independent metabolites of
      arachidonic acid and many researchers associate them with free radicals. These
      properties are shared with isoprostanes. In this article, I compare the
      properties of EDHFs and EDCFs with those of the isoprostanes and propose novel
      experiments that might identify isoprostanes as candidate molecules for EDHFs and
      EDCFs.

PMID- 11830262
TI  - Receptor-operated Ca2+ influx channels in leukocytes: a therapeutic target?
AB  - Receptor-mediated activation of leukocytes by inflammatory stimuli elicits Ca2+
      ion influx as a common and important activation mechanism that has been well
      established in the literature for over a decade. Inhibiting such receptor
      operated Ca2+ influx channels is a potentially attractive strategy for developing
      anti-inflammatory drugs to attenuate leukocyte activation. Until very recently,
      the molecular identity of these channels has been unknown, which has hampered
      drug development in this area. However, the recent explosion of molecular
      information about one particular family of non-voltage-activated Ca2+ channels,
      the transient receptor potential (TRP) channels, together with emerging knowledge
      of their distribution, function and regulation, suggests that they represent a
      key subgroup of these channels and are therefore potentially attractive drug
      targets.

PMID- 11830263
TI  - The CRF peptide family and their receptors: yet more partners discovered.
AB  - Abnormal signaling at corticotropin-releasing factor CRF1 and CRF2 receptors
      might contribute to the pathophysiology of stress-related disorders such as
      anxiety, depression and eating disorders, in addition to cardiac and inflammatory
      disorders. Recently, molecular characterization of CRF1 and CRF2 receptors and
      the cloning of novel ligands--urocortin, stresscopin-related peptide/urocortin
      II, and stresscopin/urocortin III--have revealed a far-reaching physiological
      importance for the family of CRF peptides. Although the physiological roles of
      the CRF2 receptor remain to be defined, the preclinical and clinical development
      of specific small-molecule antagonists of the CRF1 receptor opens new avenues for
      the treatment of psychiatric and neurological disorders.

PMID- 11830264
TI  - Smoking and ischemic stroke: a role for nicotine?
AB  - Cigarette smoking is a preventable risk factor for ischemic stroke. The
      mechanisms by which smoking contributes to stroke are poorly understood and the
      role of nicotine in this process is controversial. Although nicotine administered
      transdermally and orally does not appear to have as many associated health risks
      as do cigarettes, nicotine does have acute vasoactive and mitogenic effects on
      vascular tissues. Nicotine might alter the function of the blood-brain barrier
      and disrupt normal endothelial cell function. Some of the detrimental effects of
      nicotine are prevented by nicotinic acetylcholine receptor antagonists. However,
      recent studies indicate that nicotine might also interact with intracellular
      signaling pathways that are independent of acetylcholine receptors. In light of
      these recent developments, the impact of nicotine on cerebrovascular pathology
      should not be dismissed.

PMID- 11830265
TI  - Carbonic anhydrase gating of attention: memory therapy and enhancement.
AB  - Enhancement of memory acquisition and recall represents an important
      pharmacological goal in the treatment of cognitive disorders. In addition to its
      involvement in pH regulation, HCO3- reabsorption and CO2 expiration, carbonic
      anhydrase plays a crucial role in signal processing, long-term synaptic
      transformation and attentional gating of memory storage. Carbonic anhydrase
      dysfunction impairs cognition and is associated with mental retardation,
      Alzheimer's disease and aging. The pharmacological profile of carbonic anhydrase
      has been refined and specific activators have been developed. In this article, an
      integrated view of the involvement of carbonic anhydrase activity in synaptic
      plasticity and cognition will be presented, with particular focus on attentional
      gating of spatial learning and memory.

PMID- 11830266
TI  - Mechanisms of inverse agonism at G-protein-coupled receptors.
AB  - Many drugs with important therapeutic actions that had been assumed to be
      antagonists at G-protein-coupled receptors (GPCRs) have been shown to be inverse
      agonists. For both basic pharmacology and drug design it is important to
      understand the mechanisms whereby these drugs achieve their effects. It had been
      assumed that these drugs achieved their effects by stabilizing an inactive state
      of the receptor (R) at the expense of a partially activated state (R*). In this
      article, I consider this and other mechanisms that could explain inverse agonist
      actions, and conclude that more than one mechanism can apply to inverse agonism
      at GPCRs.

PMID- 11830267
TI  - Antidotes.

PMID- 11830270
TI  - Orexins and feeding: special occasions or everyday occurrence?
AB  - Neurons expressing prepro-orexin, the precursor of orexin-A and -B, are found in
      the lateral hypothalamic area, a region classically implicated in driving
      feeding. Orexin-A induces feeding transiently when injected centrally, and food
      intake can be decreased when orexin action is disrupted by immunoneutralization
      of orexin-A, or by pharmacological blockade of orexin receptors, or by transgenic
      knockout of orexin. Here, we argue that orexin neurons may act to stimulate
      feeding in the short term, and that important regulatory signals may be a fall in
      plasma glucose (stimulatory), countered by satiety signals generated by eating,
      such as gastric distention (inhibitory).

PMID- 11830271
TI  - Orexins/hypocretins in the ob/ob mouse: hypothalamic gene expression, peptide
      content and metabolic effects.
AB  - Orexins (forms A and B) belong to a new family of peptides that, as neuropeptide
      Y (NPY), stimulate food intake when centrally injected. The ob/ob mouse is a well
      characterized model of hyperphagia and obesity associated with strong metabolic
      disturbances and a central dysregulation of peptides involved in the control of
      feeding. In the present report, we investigated the hypocretin (Hcrt)/orexin (OX)
      peptide pathway in lean and ob/ob mice. Prepro-Hcrt/OX mRNA expression, measured
      by in situ hybridization was restricted to the lateral hypothalamus area. It was
      significantly decreased in ob/ob mice (-18%; p<0.01). When estimated by real time
      RT-PCR in the whole hypothalamus, this decrease amounted to 65% (p<0.001). Hcrt
      1/OX-A peptide concentrations, measured by RIA in microdissected hypothalamic
      nuclei were high in the lateral hypothalamus (LH) and lower in the arcuate (ARC)
      and paraventricular nuclei (PVN). In ob/ob mice, OX-A levels were significantly
      lower than in lean mice in the LH (-34%; p<0.02) and in the PVN (-72%; p<0.005).
      Acute intracerebroventricular injection of Hcrt-1/OX-A (1-10 nmol) stimulated
      feeding in lean, but not in ob/ob mice, whereas Hcrt-2/OX-B (1-10 nmol) had the
      opposite effect. Acute third ventricle (i3vt) injections of Hcrt/OX peptides in
      ob/ob mice transiently increased their metabolic rate and stimulated lipid
      substrate utilization. These findings provide direct evidence that Hcrt/OX
      peptides are down-regulated in the hypothalamus of ob/ob mice, contrary to the
      NPY system. The present data argues that Hcrt/OX peptides are not primarily
      responsible for the metabolic syndrome of the ob/ob mice. The diminution in the
      OX tone might participate in a counterregulatory system necessary to limit the
      adverse effects of NPY on food intake and body weight.

PMID- 11830272
TI  - Characterization of orexins (hypocretins) and melanin-concentrating hormone in
      genetically obese mice.
AB  - Orexins (hypocretins) and the melanin-concentrating hormone (MCH) are
      neuropeptides localized to the lateral hypothalamic area and are potential
      regulators of energy homeostasis. Using highly sensitive radioimmunoassay for
      orexins and MCH, we determined their contents in the lateral hypothalamus (LH) of
      genetically obese ob/ob and db/db mice and their controls, C57BL/6J and
      C57BL/KSJ. The orexin contents in the lateral hypothalamus significantly
      increased in the ob/ob mice, whereas the orexin contents significantly decreased
      in the db/db mice. Mature orexin-A and -B peptides were the major endogenous
      orexin molecules in the lateral hypothalamus. Conversely, the MCH contents in the
      lateral hypothalamus of both obese mice increased compared to the control mice.
      MCH contents in the lateral hypothalamus were two- to five-fold higher than that
      of orexin contents. These results suggest that the regulatory mechanism of orexin
      and MCH may be different in the genetically obese mice.

PMID- 11830273
TI  - Feeding and activity induced by orexin A in the lateral hypothalamus in rats.
AB  - Orexin A injected into the lateral hypothalamus (LH) stimulates feeding and
      activates neurons in brain sites regulating feeding and arousal. The feeding
      effects of orexin A have been demonstrated during the light cycle, a time when
      rats are normally resting, and the effect of orexin A on activity after injection
      into the LH has not been previously measured. Thus, it is unclear whether LH
      orexin A-induced feeding is secondary to enhanced arousal. To address this, LH
      cannulated rats habituated to a running wheel were injected with either orexin A
      (1000 pmol) or vehicle during light and dark cycles. Food intake and running
      wheel rotations were measured for 2 h. Spontaneous physical activity (SPA) was
      also measured during the dark cycle. During the light cycle, orexin A in the LH
      stimulated feeding in the presence and absence of a running wheel and increased
      number of running wheel rotations in the presence and absence of food. During the
      dark cycle, orexin A in the LH induced SPA (+/- presence of food), but had no
      effect on feeding. These data show that LH orexin A stimulation of feeding is not
      always coincident with increased activity, suggesting that feeding induced by LH
      injected orexin A is not consequent to enhanced arousal.

PMID- 11830275
TI  - Orexin gene expression and regulation by photoperiod in the sheep hypothalamus.
AB  - Hypothalamic orexin gene expression has not been reported in the ruminant. Here,
      we describe the localization of preproorexin mRNA in the ovine lateral
      hypothalamic area (LHA) and zona incerta (ZI) using in situ hybridization. The
      hypothalamic localization of the orexin gene expression was similar in sheep to
      rodent models. Since appetite in sheep is seasonally (photoperiodically)
      regulated, we compared the amounts of preproorexin mRNA between long- (LD) and
      short-day (SD) photoperiods in both freely feeding (food intake is 20% higher in
      LD than SD) and food-restricted sheep (50% liveweight maintenance for 11 weeks).
      Gene expression was higher in SDs than in LDs but was not affected by chronic
      food restriction. In a second study, hypothalamic orexin gene expression in
      castrate sheep was not affected by a 4-day fast, irrespective of gonadal steroid
      (estradiol) replacement, and was not affected by the gonadal steroid per se. The
      results demonstrate the sensitivity of orexin gene expression to photoperiod, but
      up-regulation occurs in SDs when the appetite is characteristically low and no
      sensitivity to imposed changes in food intake. This supports the concept that
      orexins may not have a primary role in appetite regulation and correction of
      negative energy balance but since the sheep breed only in SDs, their role in
      seasonal reproductive activation deserves further study.

PMID- 11830274
TI  - Orexin/hypocretin neurons: chemical phenotype and possible interactions with
      melanin-concentrating hormone neurons.
AB  - We showed earlier that a specific neuron population of the rat lateral
      hypothalamus, differing from the codistributed melanin-concentrating hormone
      (MCH) neurons, express both dynorphin (DYN) and secretogranin II (SgII) genes. We
      demonstrated later that this population corresponds in fact to the newly
      identified orexin/hypocretin (OX/Hcrt) neurons. In the present study, by
      revisiting the chemical phenotype of these neurons, we confirm that all of them
      contain DYN B- and SgII-immunoreactive materials. The roles played by these
      peptide/protein in OX/Hcrt neurons are still unclear. Double immunocytochemical
      stainings highlight putative somasomatic, axosomatic and axodendritic contacts
      between OX/Hcrt and MCH neurons. Adding OX/Hcrt to the culture medium of
      hypothalamic slices from 8-day-old rats results either in a significant increase
      of MCH mRNA after 24 h survival or a strong fall after 10 days culture. These
      results taken together suggest that OX/Hcrt can directly and/or indirectly affect
      MCH expression, and that both OX/Hcrt and MCH neuron populations interact to
      respond in a coordinated manner to central and peripheral signals.

PMID- 11830276
TI  - Effects of orexins on energy balance and thermoregulation.
AB  - Intracerebroventricular injections of 10-20-microg orexin-A induce food intake in
      rats for about 30 min, or enhance fasting-induced hyperphagia. In
      thermoregulatory studies, an amount of 2 microg of the peptide causes
      hypometabolism and hypothermia in the same period. The thermoregulatory reaction
      can be demonstrated at moderately cool environments, mainly after slight food
      deprivation. Both the ingestive and the thermoregulatory reactions are more
      pronounced in cold-adapted animals. Pretreatment with D-Tyr27,36,D-Thr32-NPY(27
      36), a peptide-antagonist of NPY, prevents the hypothermia. It is concluded that,
      probably through NPY activation, orexin-A is involved primarily in the regulation
      of energy status of the body (as an anabolic agent), and not simply in the
      regulation of either food intake or body temperature. This anabolic response is
      followed by a late and more sustained catabolic phase characterized by absence of
      food intake, increased metabolism and dose-dependent hyperthermia, which
      hyperthermia cannot be suppressed by the NPY-antagonist. In contrast to orexin-A,
      neither hyperphagia nor suppression of refeeding hyperphagia, but dose-dependent
      hyperthermia follows injections of orexin-B, suggesting that this peptide has
      neither coordinated anabolic nor coordinated catabolic effects on energy balance.

PMID- 11830277
TI  - The role of NPY in the mediation of orexin-induced hypothermia.
AB  - The mediation of orexin-A-induced hypothermia was investigated. Different doses
      of orexin-A (140-560 pmol) were administered intracerebroventricularly (i.c.v.)
      to adult male rats, and the colon temperature was used as an index of the
      thermoregulatory action. Orexin-A decreased both the basal colon temperature and
      the lipopolysaccharide-induced fever and exhibited a bell-shaped dose-response
      curve. I.c.v. pretreatment with neuropeptide Y (NPY) antiserum 24 h before orexin
      administration significantly decreased the hypothermic effect of orexin-A. These
      data strengthen the hypothesis that this appetite-regulating peptide might also
      play a role in thermoregulation, and its hypothermic effect seems to be mediated
      at least partially by NPY.

PMID- 11830279
TI  - Orexins and adipoinsular axis function in the rat.
AB  - Orexin A and B are recently identified as peptides that are derived from the same
      precursor and their expression is highly specifically localized in neurons
      located in the lateral hypothalamic area, a region implicated in the feeding
      behaviour. These peptides appear to be a part of a complex circuit that
      integrates the aspects of energy metabolism, cardiovascular function, hormone
      homeostasis and sleep/wake behaviours. The functional linking of orexins with
      leptin and insulin suggests the possibility of its involvement in the regulation
      of the adipoinsular axis, and the present investigation was designed to examine
      the potential role of orexins in this axis regulation. In all the tested doses
      (8, 16 and 40 nmol/kg body weight (b.w.)), subcutaneous (s.c.) injections of
      orexin A caused the significant increase in insulin and leptin blood levels.
      These elevations were observed 60 and 120 min after peptide administration. On
      the other hand, after the orexin B administration, elevated insulin and leptin
      blood concentrations were found only at 60 min of the experiment, and in that
      time point, the increases were comparable to that evoked by orexin A. In
      comparison with the control animals, the administration of orexins for 7 days
      resulted in a significant gain in body weight. Prolonged administration of either
      orexin A or orexin B significantly elevated insulin and leptin blood
      concentrations. Under these conditions, the orexin A effect on the leptin
      secretion was more marked than on the insulin secretion, and this difference is
      reflected by the lowered insulin/leptin molar ratio. These results suggest that
      orexins play an important role in the adipoinsular axis function and may be a
      significant regulator of both insulin and leptin secretion. In this regard, we
      suggest the updated functional model of Kieffer and Habener [Am. J. Physiol.:
      Endocrinol. Metab. 27 (2000) E1] that proposed the adipoinsular axis. Our model
      is extended by the probable humoral links between orexins and leptin and orexins
      and insulin and points on the dependence of the effects evoked by orexins, leptin
      and insulin on the blood glucose levels.

PMID- 11830278
TI  - Chronic intraparaventricular nuclear administration of orexin A in male rats does
      not alter thyroid axis or uncoupling protein-1 in brown adipose tissue.
AB  - Orexin A, synthesised in the posterolateral hypothalamus, has widespread
      distribution including the paraventricular nucleus (PVN), which is rich in
      thyrotropin-releasing hormone (TRH) neurones. Nerve fibres in the PVN synapse on
      neurones that send polysynaptic projections to brown adipose tissue (BAT), which
      is important in thermogenesis. A number of observations suggests orexin A may be
      involved in regulation of metabolism and thermogenesis. We investigated the
      effect of orexin A injected intracerebroventricularly (ICV) on thyroid
      stimulating hormone (TSH) and thyroid hormones in male rats. We then examined the
      effect of chronic iPVN injections of orexin A on plasma TSH and uncoupling
      protein-1 (UCP-1) protein in BAT. Orexin A (3 nmol) administered ICV
      significantly suppressed plasma TSH at 10 and 90 min. Orexin A (0.3 nmol)
      administered into the PVN twice daily for 3 days significantly increased day-time
      2-h food intake, but did not significantly alter nocturnal food intake. Though
      chronic iPVN orexin A altered diurnal food intake, there was no effect on 24-h
      food intake or body weight. Furthermore, orexin A administered chronically into
      the PVN did not alter UCP-1 level in BAT, or plasma hormones relative to saline
      injected animals. Chronic iPVN orexin A does not appear to influence
      thermogenesis through activation of UCP-1 or the thyroid axis.

PMID- 11830280
TI  - Pressor response to microinjection of orexin/hypocretin into rostral
      ventrolateral medulla of awake rats.
AB  - Orexin A (or hypocretin 1)-immunoreactive neurons in the rat lateral hypothalamus
      project to several areas of the medulla oblongata that are closely associated
      with cardiovascular regulation. The present study was undertaken to further
      strengthen the hypothesis that orexin A accelerates cardiovascular response by
      activating sympathoexcitatory neurons in the rat rostral ventrolateral medulla
      (RVLM). First, immunohistochemical studies revealed the presence of orexin A
      immunoreactive fibers in the RVLM. Double labeling the sections with orexin A-
      and tyrosine hydroxylase (TH)-antisera further showed that orexin A
      immunoreactive fibers are in close proximity with TH-immunoreactive neurons, some
      of which may be barosensitive, bulbospinal neurons in the RVLM. Second,
      microinjection of orexin A (6.35, 12.7 and 38.1 microM) into the RVLM, which was
      verified later by histological examination, caused a significant increase of mean
      arterial pressure (MAP) and a moderate increase of heart rate (HR) in awake rats.
      L-glutamate (33.3 mM) injected into the same sites, caused a larger increase in
      MAP, but a decrease in HR; whereas, saline injection was without significant
      effect. Results from this study suggest that orexin A, which may be released from
      the nerve fibers originating from the neurons in the lateral hypothalamus, acting
      on RVLM neurons in the medulla, increases sympathetic outflow targeted to the
      heart and blood vessels in awake animals.

PMID- 11830281
TI  - Selective excitation of GABAergic neurons in the substantia nigra of the rat by
      orexin/hypocretin in vitro.
AB  - Dysfunction of the orexin/hypocretin neurotransmitter system leads to the sleep
      disorder narcolepsy. Narcolepsy is characterized by excessive daytime sleepiness
      and the occurrence of cataplexy--a sudden loss of muscle tone triggered by
      emotionally arousing events. Both symptoms can be treated with drugs that act on
      dopaminergic systems. Here we have investigated the effect of orexins on the
      firing of dopaminergic and GABAergic neurons of the substantia nigra (SN) in
      brain slices. Surprisingly, dopaminergic neurons in pars compacta were unaffected
      by orexins. In contrast, bath application of orexin A (100 nM) or orexin B (5-300
      nM) greatly increased the firing rate of GABAergic neurons in pars reticulata.
      The orexin B-mediated excitation was unaffected by blocking synaptic transmission
      (using low-Ca2+/high-Mg2+ solution). However, the effect of orexin B was reduced
      significantly by thapsigargin (1 microM) and inhibitors of protein kinase A. The
      presence of orexinergic fibres in the SN pars reticulata was demonstrated by
      immunohistochemical methods with the fibre density increasing in the rostrocaudal
      direction. The orexin excitation of SN reticulata cells may help to maintain
      their high firing rate during waking. Furthermore, the absence of orexin effects
      in narcolepsy may predispose affected individuals to attacks of cataplexy.

PMID- 11830282
TI  - Neuronal effects of orexins: relevant to sympathetic and cardiovascular
      functions.
AB  - Orexin A and B, also called hypocretin 1 and 2, were recently discovered in the
      hypothalamus. This organ, in which a number of neuropeptides have been
      demonstrated to stimulate or suppress food intake, is considered important for
      the regulation of appetite and energy homeostasis. Orexins were initially
      reported as a regulator of food intake. More recent reports suggest their
      possible important roles in the multiple functions of neuronal systems, such as
      narcolepsy, a sleep disorder. Orexins and their receptors are distributed in
      neural tissue and brain regions involved in the autonomic and neuroendocrine
      control. Functional studies have shown that these peptides evoke changes in
      cardiovascular and sympathetic responses. The data from our in vivo and in vitro
      studies suggest that the peptide acting on neurons in the hypothalamic
      paraventricular nucleus increases the cardiovascular responses. This review will
      focus on the neural effects of orexins and how these peptides may participate in
      the regulation of cardiovascular and sympathetic functions.

PMID- 11830283
TI  - Orexin actions in hypothalamic paraventricular nucleus: physiological
      consequences and cellular correlates.
AB  - Orexinergic neurons originating in the perifornical, lateral hypothalamus project
      to numerous brain sites including neuroendocrine centers known to be important in
      the physiologic response to stress. Those projections suggest an action of
      endogenous orexin on adrenocorticotropin (ACTH) release, either by
      neuromodulatory effects in the paraventricular nucleus (PVN), or by
      neuroendocrine actions in the pituitary gland following release into the median
      eminence. We sought to determine if exogenously applied orexin A might act in the
      brain to alter ACTH release and to determine if a site of action in the
      hypothalamic paraventricular nucleus could be identified. Cerebroventricular
      administration of orexin A in conscious male rats resulted in a dose-related
      elevation in circulating ACTH levels. At 30 min post-infusion, ACTH levels were
      elevated 2.5-fold by the low dose of orexin A (0.3 nmol), 5.7-fold by the middle
      dose tested (1.0 nmol), and 7.5-fold by the highest dose tested (3.0 nmol).
      Pretreatment with a CRH-antagonist (i.v.) blocked the ability of i.c.v.
      administered orexin A to activate the hypothalamo-pituitary-adrenal (HPA) axis.
      Bath application of orexin A in hypothalamic slice preparations resulted in
      depolarizations (8.0+/-0.6 mV), accompanied by increases in spike frequency in
      identified magno- and parvocellular neurons in the PVN. Our data suggest a
      potential role for endogenous orexin in the hypothalamic regulation of stress
      hormone secretion.

PMID- 11830284
TI  - The action of orexin A on passive avoidance learning. Involvement of
      transmitters.
AB  - The action of orexin A on one-way passive avoidance learning was studied in rats.
      Orexin A administered into the lateral brain ventricle in conscious rats
      facilitated learning, the consolidation of learning and also retrieval processes
      in a dose-dependent manner in a passive avoidance paradigm. The involvement of
      transmitters was studied by pretreating the animals with receptor antagonists,
      which had proved to be effective with other neuropeptides in attenuating or
      blocking the action of orexin A. The following receptor blockers were used:
      haloperidol, phenoxybenzamine, propranolol, atropine, bicuculline, naloxone and
      nitro-L-arginine, which can block nitric oxide synthase. In the doses used all of
      the receptor blockers attenuated, but none of them fully blocked the action of
      orexin A on the consolidation of passive avoidance learning. The results
      demonstrate that orexin A is able to facilitate learning, consolidation of
      learning and also retrieval processes in a passive avoidance paradigm. A number
      of transmitters could be involved in the action of consolidation, but none of
      them is absolutely essential.

PMID- 11830285
TI  - Interaction of the hypocretins with neurotransmitters in the nucleus accumbens.
AB  - The hypocretins (hcrt1 and hcrt2), also known as orexins, are two neuropeptides
      derived from the same precursor, expressed in a few thousand cells in the lateral
      hypothalamus. Hypocretin-containing cells project throughout the brain, including
      ascending projections to the olfactory bulb and cerebral cortex, through the
      medial septum and the nucleus accumbens. Here, we have studied the interactions
      of the hypocretins with different neurotransmitters by patch clamp recording of
      acutely dissociated cells from the nucleus accumbens. Application of hcrt1 or
      hcrt2 decreased postsynaptic NMDA currents, enhanced GABA currents but did not
      affect glycine-activated conductances. Our results strongly suggest that the
      hypocretin peptides may be inhibitory peptides, probably via binding hcrt
      receptor 2.

PMID- 11830286
TI  - Involvement of the serotonergic system in orexin-induced behavioral alterations
      in rats.
AB  - We have demonstrated involvement of the serotonergic system in orexin-induced
      behavioral responses in rats. Orexin-A and -B (hypocretin-1 and -2) significantly
      increased total locomotor activity when administered centrally. They also induced
      behavioral alterations; increasing grooming, face washing and wet dog shaking in
      rats. Haloperidol inhibited orexin-induced hyperlocomotion and these behavioral
      alterations. Serotonin antagonists, ritanserin and metergoline, did not attenuate
      orexin-induced hyperlocomotion but partly inhibited orexin-induced behavioral
      alterations. These results suggest that the dopaminergic system might be involved
      in orexin-induced hyperlocomotion, while both the serotonergic system as well as
      the dopaminergic system might be involved in orexin-induced behavioral responses.

PMID- 11830287
TI  - Effects of orexin on cultured porcine adrenal medullary and cortex cells.
AB  - New orexigenic peptides called orexins have recently been described in the
      neurons of the lateral hypothalamus and perifornical area. No orexins have been
      found in the adipose tissues or visceral organs, including the adrenal gland.
      However, expression of the orexin receptor (OXR) in the rat adrenal gland has
      been reported. With regard to the effects of orexins on peripheral organs, we
      previously reported that orexins suppress catecholamine synthesis and secretion
      in the rat pheochromocytoma cell line PC12. To further clarify the
      pharmacological effects of orexins on peripheral organs, we examined the effects
      of orexin-A on catecholamine, cortisol, and aldosterone secretion, using cultured
      porcine adrenal glands. We initially confirmed the expression of the orexin
      receptor (OXR-1) in cultured porcine adrenal medulla and cortex. Orexin-A (1000
      nM) significantly increased the release of both epinephrine (E) and
      norepinephrine (NE) from porcine adrenal medullary cells. Similarly, orexin-A (>
      or = 100 nM) significantly increased the release of both cortisol and aldosterone
      from porcine adrenal cortex cells. Orexin-A (100 nM) significantly inhibited
      basal and the PACAP-induced increase in cAMP levels in adrenal medullary cells.
      Conversely, orexin-A (>o = 100 nM) significantly increased the cAMP level in
      adrenal cortex cells. These results indicate that orexin-A induces the release of
      catecholamine from porcine adrenal medullary cells, and aldosterone and cortisol
      from the cortex cells and has opposite effects on cAMP levels in adrenal medulla
      and cortex.

PMID- 11830288
TI  - Protein distribution of the orexin-2 receptor in the rat central nervous system.
AB  - Orexin-A and -B are neuropeptides mainly expressed in the lateral hypothalamic
      area (LHA). A role for orexins was first demonstrated in the regulation of
      feeding behaviour. Subsequently, the peptides have been implicated in the control
      of arousal. To date, two receptors for orexins have been characterised: orexin-1
      and -2 receptors (OX-R1 and OX-R2). Both receptor genes are widely expressed
      within the rat brain. Particularly high expression of both receptor genes in
      certain hypothalamic and pons nuclei could be responsible for the orexigenic and
      arousal properties of the peptides. It is, however, presently unclear if one
      given receptor subtype or both subtypes may mediate a specific biological effect
      of orexins such as an increase in food intake. We have recently reported the
      distribution of the OX-R1 protein in the rat nervous system. In this study, we
      report the distribution of the OX-R2 protein in the rat brain and spinal cord
      using specific anti-peptide antisera raised against the OX-R2 protein. We also
      assess the expression profile of the OX-R2 gene in different brain regions.
      Immunolabelling for the OX-R2 protein was observed in brain regions that
      exhibited OX-R1-like immunoreactivity (cerebral neocortex, basal ganglia,
      hippocampal formation, and many other regions in the hypothalamus, thalamus,
      midbrain and reticular formation). Differences in the OX-R1 and OX-R2
      distribution were, however, noticed in the hippocampus, hypothalamus and dorso
      lateral pons.

PMID- 11830289
TI  - Effects of restricted feeding on the activity of hypothalamic Orexin (OX)-A
      containing neurons and OX2 receptor mRNA level in the paraventricular nucleus of
      rats.
AB  - We have examined the effects of 3 weeks of food restriction on both the activity
      of neurons containing hypothalamic orexin (OX)-A and the level of OX receptor
      type 2 (OX2R) mRNA in the paraventricular nucleus (PVN) of rats. Double
      immunohistochemistry was used to examine the expression of OX-A and Fos in the
      lateral hypothalamic area (LHA), and in situ hybridization histochemistry was
      used to measure levels of OX2R mRNA in the PVN. After the period of restricted
      feeding, 20-30% of OX-A-containing neurons exhibited Fos-like immunoreactivity
      (LI). The distribution of OX-A-LI/Fos-LI cells in the food-restricted rats was
      similar to that observed in glucose-deprived rats after intracerebroventricular
      (icv) administration of 2-deoxy-D-glucose (2-DG). In addition, 3 weeks of food
      restriction caused a significant decrease in the expression of the OX2R gene in
      the parvocellular division of the PVN. These results suggest that the activation
      of OX-A-containing neurons induced by restricted feeding may be involved in
      neuroendocrine responses to food restriction.

PMID- 11830290
TI  - Anorectic, thermogenic and anti-obesity activity of a selective orexin-1 receptor
      antagonist in ob/ob mice.
AB  - A single dose of the orexin-1 (OX1) receptor antagonist 1-(2-methylbenzoxazol-6
      yl)-3-[1,5] naphthyridin-4-yl urea hydrochloride (SB-334867-A) reduces orexin-A
      induced feeding and natural feeding in Sprague Dawley rats. In this study, the
      anti-obesity effects of SB-334867-A were determined in genetically obese (ob/ob)
      mice dosed with SB-334867-A (30 mg/kg, i.p.) once daily for 7 days, and then
      twice daily for a further 7 days. SB-334867-A reduced cumulative food intake and
      body weight gain over 14 days. Total fat mass gain, determined by Dual Emission X
      ray Absorptiometry, was reduced, while gain in fat-free mass was unchanged.
      Fasting (5 h) blood glucose was also reduced at the end of the study, with a
      trend to reduced plasma insulin. Interscapular brown adipose tissue (BAT) weight
      was reduced, the tissue was noticeably darker in colour and quantitative PCR
      (TaqMan) analysis of this tissue showed a trend to an increase in uncoupling
      protein-1 mRNA expression, suggesting that SB-334867-A might stimulate
      thermogenesis. This was confirmed in a separate study in which a single dose of
      SB-334867-A (30 mg/kg, i.p.) increased metabolic rate over 4 h in ob/ob mice. OX1
      receptor mRNA was detected in BAT, and its expression was increased by 58% by
      treatment with SB-334867-A. This is the first demonstration that OX1 receptor
      antagonists have potential as both anti-obesity and anti-diabetic agents.

PMID- 11830291
TI  - Cellular localization of orexin receptors in human adrenal gland, adrenocortical
      adenomas and pheochromocytomas.
AB  - Orexin-A and -B are hypothalamic peptides derived from a precursor called prepro
      orexin and related with the regulation of the energy balance and arousal. They
      act on G protein receptors named orexin receptor 1 (OX1R) and orexin receptor 2
      (OX2R). In the present study, we used immunohistochemical techniques to detect
      the distribution of OXR in normal human adrenal gland and adrenal tumours
      (adrenocortical adenomas and pheochromocytomas). OX1R was expressed in the cortex
      of the normal human adrenal gland (glomerulosa, fasciculata and reticular zones)
      and OX2R was located in the medulla (epinephrine and norepinephrine cells). By
      the double immunofluorescence techniques, we demonstrated that virtually all
      medullar cells (epinephrine and norepinephrine cells) expressed OX2R. As was
      expected, according to the results obtained in normal tissues, cortical tumours
      (adrenocortical adenomas) were positive for OX1R but not for OX2R and conversely,
      medullar tumours (pheochromocytomas) expressed only OX2R.

PMID- 11830292
TI  - Foot/leg and udder health in relation to housing changes in Swedish dairy herds.
AB  - Monthly herd disease incidence rate or prevalence estimates in 196 Swedish
      commercial dairy herds from 1988 to 1995 were collected retrospectively from the
      official milk-recording scheme and merged with county administrative and farmers'
      data on housing and management. To study the effects of changes in housing system
      on the occurrence of veterinary-treated foot/leg disorders, clinical mastitis,
      teat injuries and high milk somatic cell counts (MSCCs), four marginal Poisson or
      negative-binomial regression models were applied to the data (6011-7063 herd
      month records), using the generalized estimating-equations method. Monthly
      observations were treated as repeated measures within herds. There were
      significant transitory increases in the incidence of clinical foot/leg disorders
      when changing from tie-stalls to cubicles and decreases in the incidences of
      clinical mastitis and teat injuries when changing from tie-stalls to cubicle or
      straw-yard systems. Effects on foot/leg health generally lasted for <18 months
      after building finish, while udder-health improvements persisted >18 months.
      Reductions in the incidence of clinical mastitis were not accompanied by any
      clear changes in the prevalence of high MSCCs.

PMID- 11830293
TI  - Maximum-likelihood estimation of sensitivity and specificity of ELISAs and faecal
      culture for diagnosis of paratuberculosis.
AB  - The accuracy of three diagnostic tests for paratuberculosis was evaluated using
      maximum-likelihood estimation of sensitivity and specificity. We also explored
      the variety of estimates that can be obtained if the tests are to be used in
      populations of different composition with regard to infection and disease states.
      Two enzyme-linked immunosorbent assays (ELISAs) were evaluated separately with
      the faecal culture (FC). The study was carried out as a cross-sectional field
      study to cover all likely states of infection with Mycobacterium avium subsp.
      paratuberculosis.The three basic assumptions for the maximum-likelihood technique
      were evaluated to validate the results. Our accuracy estimates for the ELISAs
      were not very different from those previously published, but those for faecal
      culture differed if a different cut-off value was chosen for the ELISA. If faecal
      culture was used for screening in a Danish dairy region where the median ELISA
      reading was a measure of the general disease situation, the sensitivity of the
      faecal culture was 20-25%. If faecal culture was used as a confirmatory test on
      cows with a high ELISA reading (and thus high level of antibodies), the
      sensitivity of the faecal culture would be in the range 60-70%. These results
      emphasise the importance of the composition of a target population before
      selecting a specific diagnostic test for a given purpose. We concluded that
      faecal culture is useful for confirmation but not for screening purposes.

PMID- 11830294
TI  - Risk factors for Aujeszky's disease in pig herds and detection of field virus
      antibodies in fattening pigs in the state of Yucatan, Mexico.
AB  - Two epidemiological studies were conducted from August 1997 to May 1998: a case
      control study to identify herd level risk factors for antibodies to Aujeszky's
      disease virus (ADV) in sows in the state of Yucatan, Mexico and a cross-sectional
      study to determine the prevalence of antibodies against ADV in fattening pigs. In
      the case-control study, data on herd management and biosecurity were obtained
      from all the 27 ADV known field-virus-seropositive farms (cases) and 62 randomly
      selected seronegative farms (controls) by questionnaire. Breeding animals of
      these seropositive farms had received a gE-deletion vaccine. In the cross
      sectional study, 26 farrow-to-finish farms of the 27 seropositive farms were used
      and blood samples taken from 60 fattening pigs per herd (15 pigs for each stage
      of production). Serum samples were analyzed by the screening-ELISA and gE-ELISA
      tests. In the case-control study, three of the 15 risk factors were significant.
      Odds ratios for distance to the nearest farm (< or = 2.5km), not sampling for the
      detection of ADV and herds with origin of breeding animals within the state were
      9.5, 18.1 and 8.7. In the cross-sectional study, 11 (42.3%) of the 26 sampled
      farms were seropositive to vaccine antibodies. None of the piglets were positive
      to antibodies against field virus risk--suggesting that the strategy of
      vaccinating only the breeding animals reduced the ADV infection of the piglets.

PMID- 11830295
TI  - Topical treatment of digital dermatitis associated with severe heel-horn erosion
      in a Swedish dairy herd.
AB  - Two experiments were run in a commercial dairy herd to test the efficacy of
      topical treatments of digital dermatitis associated with severe heel-horn
      erosion. In Experiment I, topical treatments with solutions of either
      glutaraldehyde or oxytetracycline were compared with foot trimming and cleansing
      alone. After trimming of all feet, one front and one rear foot in each cow were
      treated with either glutaraldehyde or oxytetracycline (regardless of dermatitis
      status), while the other feet were used as controls and only trimmed. Two hundred
      foot records were obtained from 34 Swedish Red and White and 16 Swedish Holstein
      cows. The proportions (p) of feet cured from digital dermatitis were compared
      between each group of medically treated feet and the control feet, assuming the
      feet to be independent observations with respect to curing. Oxytetracycline was
      significantly more effective than hoof trimming alone (p=0.87 and 0.34,
      respectively; P<0.001) and than glutaraldehyde (p=0.41; P=0.004). Treatment with
      glutaraldehyde was no more effective than hoof trimming alone. In Experiment II,
      a specially designed footbath with two longitudinal compartments was used to
      study the effectiveness of a solution of acidic ionised copper in preventing or
      curing digital dermatitis. The footbath--using water in one compartment--was
      constructed to make within-cow comparisons of treatment efficacy possible. The
      hoof health of 44 dairy cows (also included in Experiment I) were studied when
      the animals first were turned out to pasture and at the end of the grazing season
      (approximately 6 months later). During the grazing season, the cows were walked
      through the footbath twice daily after milking for a total of 47 days, divided
      into five separate periods ranging in length from 3 to 16 days. As judged by a
      two-sample comparison of proportions, a higher proportion of the cows' hind feet
      that were affected by dermatitis were cured by the copper solution (20/24) than
      by water alone (12/23). The copper solution had no significant preventive effect
      on healthy feet.

PMID- 11830297
TI  - Exposing culprit organic pollutants: a review.
AB  - There is a continuing need for monitoring the health of the environment due to
      the presence of pollutants. Here, we review the development and attributes of
      biosensors by which bacteria have been genetically modified to express the
      luminescence genes, i.e. to glow, in a quantified manner, in response to
      pollutants. We have concentrated on the detection of organic hydrocarbon
      pollutants and discussed the molecular mechanisms by which some of these
      chemicals act as effector molecules on the respective regulatory systems. The
      future of environmental biosensors is predictably bright. As more knowledge is
      gathered on the sensing regulatory component, the possibility of developing
      targeted or pollutant-specific biosensors is promising. Moreover, the repertoire
      of biosensors for culprit organic pollutants is expected to be enlarged through
      advances in genomics technology and identification of new sensory or receptor
      molecules. The need for pollutant detection at concentrations in the parts per
      trillion range or biosensors configured in a nanoscale is anticipated.

PMID- 11830296
TI  - Animal- and herd-level risk factors for leptospiral seropositivity among sows in
      the Mekong delta, Vietnam.
AB  - In 1998, a total of 424 sows had sera collected in the Mekong delta in Vietnam.
      Of these, 283 sows were from 151 small-scale family farms in 19 villages, and 141
      from seven large-scale state farms. The sera were subjected to the microscopic
      agglutination test (MAT) for antibodies to 13 Leptospira serovars. The overall
      leptospiral seroprevalence for titres > or =1:100 and > or =1:400, was 73 and
      29%, respectively, and was higher (P=0.001) at small- than at large-scale farms.
      The highest seroprevalence was recorded for Leptospira interrogans serovar (sv)
      bratislava (52%). At small-scale farms, higher prevalences were found to serovars
      L. interrogans sv icterohaemorrhagiae (P=0.04) and L. interrogans sv pomona
      (P=0.02). Epidemiological information (at the individual-animal and herd-levels)
      was collected with a questionnaire. The data were analysed using logistic
      multiple regression. At the animal-level, sows seropositive for L. interrogans sv
      australis and sv autumnalis had less direct contact with sows in neighbouring
      pens (odds ratio (OR)=0.3 and 0.4, respectively) and sows seronegative for L.
      interrogans sv bratislava were of lower age (OR=0.1 for seropositivity). Also,
      sows seropositive for L. interrogans sv icterohaemorrhagiae had higher odds
      (OR=5.8) if they had not been born on the farm (had been introduced to it as
      gilts). Herds seropositive for sv javanica showed association with farms not
      taking measures to control the local rodent population (OR=7.8). Serovar pomona
      was also linked to the use of artificial insemination (AI), as opposed to natural
      breeding services (OR=11.2). These results indicate that housing and management
      could affect the seroprevalence of Leptospira infection in pigs.

PMID- 11830298
TI  - A statistical procedure for the analysis of microbial communities based on
      phenotypic properties of isolates.
AB  - A novel statistical procedure for the analysis of microbial communities based on
      phenotypic properties of randomly collected isolates is presented and discussed.
      The procedure allows the representation of the microbial communities as a set of
      ellipses in a bidimensional graph. This representation is obtained by the
      following steps: (a) measurement of a set of binary phenotypic properties for n
      isolates belonging to k samples, each representing a different community; (b)
      repeated sampling by bootstrapping of the m samples, thus obtaining, for each
      community, i subsamples of j isolates; (c) calculation of the frequency of
      positive results for each test for each subsample; (d) calculation of the matrix
      of Euclidean distances between the k x i frequency vectors; (e) use of
      multidimensional scaling (MDS) to obtain a representation in two dimensions of
      the distance relationships between the frequency vectors; (f) plotting of the 95%
      confidence ellipses for the i frequency vectors of each of the k communities. By
      using both simple, synthetic microbial communities, and samples of lactic acid
      bacteria isolated from natural microbial communities (sourdoughs, compressed
      yeast, fermented sausages), it was demonstrated that the position and shape of
      the ellipses are clearly related to the composition of the community, while the
      relationship between the size of the ellipses and the phenotypical diversity of
      the community is less straightforward: while communities with very different
      diversity (measured with the Functional Evenness index and the mean taxonomic
      distance) had ellipses that were very different in size, there was no strict
      proportionality between the size of the ellipse and the diversity of the
      community. Nevertheless, the representation of microbial communities obtained by
      bootstrapping and multidimensional scaling appears to be superior to the more
      usual representation based on tabulation of the frequencies of isolates belonging
      to different clusters.

PMID- 11830299
TI  - Development of a model meat system and investigation of the growth
      characteristics and genetic stability of Escherichia coli O157:H7, in the absence
      of meat microflora.
AB  - Model meat systems were produced using both aseptically procured and irradiated
      raw minced beef to initially compare the growth characteristics of a three-strain
      mixture of Escherichia coli O157:H7 in each medium. A multiplex PCR assay
      (detecting VT1, VT2 and eae genes) was used to determine the proportion of
      individual strains recovered at each sampling time by virtue of the different
      combinations of these virulence factors encoded by each strain, and to
      investigate their genetic stability. No differences in the growth characteristics
      of the pathogen (P>0.05) were recorded in the meat matrices, irrespective of the
      preparation method, thus validating the use of irradiation to sterilise (42 kGy,
      in vacuo at <-5 degrees C) minced meat in the production of control meat matrices
      for application to further research investigations. A novel plating method,
      incorporating a period of catalase-induced resuscitation, was found to give
      significantly higher recovery of the pathogen (P<0.05) from these meat matrices
      when compared to conventional spread-plating on Trypticase Soy Agar (TSA). A
      proportion of the recovered populations, however, was found to be failing to
      produce an amplicon relating to a Verotoxin (VT) gene. A further investigation
      demonstrated that O157:H7 strain E 90197 (VT2 and eae positive) was displaying
      genetic instability during growth in and recovery from meat matrices with the
      apparent loss of the VT2 gene. An alternative VT2 and eae positive strain (ATCC
      43889) demonstrated no such genetic instability, demonstrating inter-strain
      variation for this phenomenon. Thus, it should be considered that an essential
      pre-requisite to studies relying upon the maintenance of the pathogenic potential
      of E. coli O157:H7 should be an evaluation of the genetic stability of proposed
      strains of this serotype.

PMID- 11830300
TI  - Quantitative reverse transcription polymerase chain reaction analysis of
      Porphyromonas gingivalis gene expression in vivo.
AB  - An etiological relationship between periodontitis, a significant oral health
      problem, and the anaerobe Porphyromonas gingivalis may be related to the
      expression of a variety of putative virulence factors. The objective of the
      experiments described here was to develop a quantitative reverse transcription
      polymerase chain reaction (QRT-PCR) method to examine P. gingivalis gene
      expression in human dental plaque from periodontitis subjects. PCR primers and
      probes for six target genes representing putative virulence factors were chosen
      and evaluated in vitro for specificity. A potential cross-reactivity level of
      only 10 copies/10(7) whole genomic equivalents was occasionally observed with non
      P. gingivalis microbes. P. gingivalis cells stressed in vitro by a 5 degrees C
      temperature increase showed a rapid rise in the mRNA associated with the
      molecular chaperons (htpG, dnaK, groEL), SOD (sodA) and gingipain (rgp-1) genes.
      We examined the stability of bacterial RNA in plaque specimens and found no
      significant difference in the amount of RNA obtained before or after storage 3
      months in a stabilizing buffer (p=0.786, t-test). Sixty-five percent of plaque
      samples obtained from two clinical locations contained P. gingivalis; there was a
      mean level of gene expression (fold increase) for all samples tested for groEL,
      dnaK, htpG, sodA, PG1431 and rgp-1 of 0.84+/-2.03 to 7.85+/-10.0. ANOVA showed
      that the levels of stress gene transcription for dnaK and htpG were significantly
      elevated (p<0.05) at diseased sites; groEL gene transcription approached
      statistically significant elevation (p=0.059). We found correlations between
      probing depth and increased transcription of groEL, htpG and rgp-1 and between
      attachment loss and htpG. When sorted by disease status, we detected correlations
      between disease status and elevated expression of dnaK and htpG.

PMID- 11830301
TI  - Comparison of two methods for serotyping Ureaplasma urealyticum clinical
      isolates.
AB  - A newly developed enzyme linked immunosorbent assay (ELISA) method using
      monoclonal antibodies (MAbs) to the 14 serotypes of Ureaplasma urealyticum was
      compared to immunofluorescence assay (IFA) for serotyping U. urealyticum clinical
      isolates. Of the 102 vaginal isolates of U. urealyticum, five strains were lost
      and were excluded from analysis. Of the 97 strains analysed, a total of 86 (89%)
      strains were typeable by ELISA and a total of 89 (92%) strains were typeable by
      IFA. Eighty-six strains were typeable by both methods, three by IFA only and
      eight strains were not typeable neither by ELISA nor by IFA. Of the 86 strains
      typeable by both methods, complete concordance in serotyping results was found.
      The three strains not typeable by ELISA were typeable as serotype 4 by IFA. These
      three strains were reanalysed by ELISA after major modifications of the antigen
      preparation and were typeable as serotype 4. In conclusion, the ELISA was found
      suitable for serotyping clinical isolates. However, since the ELISA had a
      somewhat lower performance than IFA, strains not typeable by ELISA, should be
      retested by another technique such as IFA.

PMID- 11830302
TI  - Construction of transcriptional and translational lacZ gene reporter plasmids for
      use in Streptococcus mutans.
AB  - Reporter genes have become standard genetic tools used to evaluate either the
      transcriptional or the translational activity associated with genes of interest,
      whose products cannot be easily assayed. The lacZ gene from Escherichia coli has
      been used very effectively to quantify such regulated activities in many
      different organisms. This report describes the construction of a pair of plasmids
      that may be used for either transcriptional or translational lacZ gene fusions in
      Streptococcus mutans. The translational E. coli beta-galactosidase gene (lacZ)
      fusion plasmid, pALH109, as well as the transcriptional lacZ gene fusion plasmid,
      pALH122, have been used successfully in S. mutans to measure the activity of
      various PTS genes. Both plasmids employ fusions with the E. coli lacZ gene that
      can be easily quantified using standard O-nitrophenyl-beta-D-galactopyranoside
      (ONPG) based enzyme assays or the more sensitive fluorometric assays using 4
      methyl-umbelliferyl beta-D-galactopyranoside (MUG) as the enzyme substrate.
      Currently, there has been only one other report of the use of lacZ as a gene
      reporter in S. mutans. The plasmids described in this paper will provide new
      tools and techniques for the analysis of S. mutans gene regulation. In addition,
      we have compiled the complete nucleotide sequences of these gene reporter
      plasmids.

PMID- 11830303
TI  - Enumeration of small ciliates in culture by flow cytometry and nucleic acid
      staining.
AB  - We developed a fast and simple protocol for accurate quantification of small
      freshwater ciliates by flow cytometry (FCM). The ciliates were stained with
      several nucleic acid stains such as TO-PRO-1, YO-YO-1 and PicoGreen, and analysed
      by a commercially available flow cytometer. The method was tested with cultures
      of the prostomatid species Urotricha farcta and Balanion planctonicum, including
      the small cryptophyte Cryptomonas sp. as food. Of the dyes tested, TO-PRO-1 gave
      the best results. Flow cytometric results agreed well with microscopic counts.
      Due to its greater speed and accuracy, FCM was superior to light microscopy. FCM
      was also superior to electronical particle counting and sizing (EPCS). Of
      particular importance, FCM in combination with TO-PRO-1 staining allowed
      unequivocal discrimination in cases of overlapping size distributions between the
      target population (i.e., the ciliate predators) and other particles (the
      cryptophyte prey, detritus).

PMID- 11830304
TI  - Improved molecular detection of Burkholderia cepacia genomovar III and
      Burkholderia multivorans directly from sputum of patients with cystic fibrosis.
AB  - Optimum detection of the Burkholderia cepacia complex (BCC) from sputum of
      patients with cystic fibrosis (CF) is essential in preventing patient-to-patient
      transmission of this organism. The aim of this study was to develop an improved
      PCR assay with reference to sensitivity for the direct detection of BCC organisms
      from CF sputum employing the recA locus. The sensitivity results of three recA
      PCR assays were compared using various combinations of previously published
      primers. These included (i) a single-round approach using the primer set
      BCR1/BCR2, yielding a 1036-bp product, (ii) a single-round approach using the
      primer set BCR1/Mr, yielding a 465-bp product, and (iii) a semi-nested PCR (SN
      PCR) approach using the primer set BCR1/BCR2 followed by BCR1/Mr. The sensitivity
      of these assays were determined by spiking B. cepacia-free sputum with known
      numbers of four strains of BCC, namely, genomovar II [B. multivorans] (C1576),
      genomovar IIIa (C5424, C6433) and genomovar IIIb (C1394). Following optimization,
      the chosen assay was performed on 14 patients. Employment of the single-round
      assay with BCR1/BCR2 was the least sensitive with a detection threshold of 10(7)
      cfu/g sputum for GIIIa and GIIIb, and 10(8) cfu/g sputum for GII. Sensitivity was
      improved by targeting the smaller amplification region of the recA locus (465 bp)
      employing the BCR1/Mr primer pair, in combination with a single-round approach,
      whereby the detection threshold was improved by 1 log for each genomovar.
      Employment of the semi-nested assay demonstrated optimum sensitivity, whereby the
      detection threshold increased to 10(1) and 10(2) cfu/g sputum for genomovar
      IIIa/IIIb and genomovar II, respectively. Subsequent genomovar characterisation
      can be performed by sequencing of the PCR amplicon without the need for culture
      which may be beneficial in patients in the initial stages of colonisation or who
      are transiently colonised and who may be culture-negative for BCC.

PMID- 11830305
TI  - PCR ligation mutagenesis in transformable streptococci: application and
      efficiency.
AB  - PCR ligation mutagenesis is a novel technique that can easily be adapted for many
      gene modification purposes. Successful application of this versatile technique
      involves sequence identification of the target gene region, creation of a
      mutagenic construct consisting of two gene-flanking proximal sequences
      specifically ligated to a selectable marker, and incorporation of this construct
      into the genome via genetic transformation and homologous recombination. In this
      study, we demonstrate the use of PCR, followed by restriction digestion and re
      ligation to generate transforming constructs for the rapid deletion of open
      reading frames in transformable streptococci. Moreover, we characterized the
      dependence of transformation efficiency for mutant generation on the length of
      the homologous regions harbored by the mutagenic construct. Our results indicated
      that PCR ligation mutagenesis could be reliably employed for the systematic
      generation of gene deletion mutants in both highly transformable Streptococcus
      mutans and S. pneumoniae. Evaluation of the method showed a strong influence of
      the length of homologous flanking region on integration efficiency.

PMID- 11830307
TI  - A multicentre randomized/controlled trial of a conventional versus modestly
      accelerated radiotherapy in the laryngeal cancer: influence of a 1 week
      shortening overall time.
AB  - BACKGROUND AND PURPOSE: To compare in a phase III study the loco-regional
      control, disease-free survival and overall survival induced by an accelerated
      regimen (AF) as compared with conventional regimen (CF) and to analyze the early
      and late post-radiation morbidity in both arms. MATERIALS AND METHODS: Patients
      with age < or = 75, WHO 0-1, suitable for a radical course of radiotherapy T1-T3,
      N0, M0, stage of glottic and supraglottic laryngeal cancer were randomized to
      either CF: 66Gy given in 33 fractions over 45 days or AF: 66Gy given in 33
      fractions over 38 days (2 fractions every Thursday). A total of 395 patients were
      included from 05.1995 to 12.1998. RESULTS: Early toxicity: At the end of
      radiotherapy patients treated with AF complained for more severe reactions than
      patients treated with CF. In 8 weeks after treatment completion patients treated
      with AF complained only for more severe pain on swallowing (P=0.027). In 4 months
      after treatment completion all types of toxicity except for skin teleangiectasia
      (P=0.001) were similar in the two groups. Loco-regional control: comparison
      between CF and AF showed no difference in terms of loco-regional control
      (P=0.37). CONCLUSIONS: The improvement in AF in terms of loco-regional control is
      estimated to be 3-5% in comparison with conventional regimen and is not
      significant. The intensity of reactions after 4 months was similar in both arms,
      what suggests the possibility of further shortening of the overall time by few
      days or enhancing the total dose within the limits of acceptable morbidity.

PMID- 11830309
TI  - Curative radiotherapy for a second primary lung cancer arising after
      pneumonectomy -- techniques and results.
AB  - BACKGROUND AND PURPOSE: Only limited data exist on the outcome of curative
      radiotherapy in patients who develop a second primary lung tumour after
      pneumonectomy. The treatment of eight such patients is described. MATERIALS AND
      METHODS: The case records of patients who underwent curative radiotherapy for
      stage I non-small cell lung cancer after a previous pneumonectomy were reviewed.
      Treatment was delivered using 3D external radiotherapy to a dose of 50-70 Gy, in
      once-daily fractions of 2-2.5 Gy. An endobronchial brachytherapy boost was used
      in three patients. Original treatments were re-planned in an attempt to minimize
      the volume of irradiated lung. RESULTS: A complete remission was achieved in five
      (of six) evaluable patients, but two patients subsequently developed a local
      relapse. All patients survived for a minimum of 1 year after treatment. Only one
      patient developed significant (grade 2) radiation pneumonitis. When treatments
      were re-planned to optimize beam arrangements, and when customized blocks were
      used, the mean lung volume receiving > or = 20 Gy (calculated for 70 Gy)
      decreased from 24.6+/-4.1 (range, 18-31%) to 17.3+/-5.1% (range, 12-26%).
      Similarly, the radiation conformity index improved from 0.44+/-0.11 to 0.61+/
      0.06. CONCLUSIONS: Involved-field radiotherapy can be curative in patients who
      develop a new lung tumour after pneumonectomy. Recent advances in defining target
      volumes, treatment planning and delivery are likely to improve upon these
      results.

PMID- 11830308
TI  - Adjuvant radiotherapy in non-small cell lung cancer with pathological stage I:
      definitive results of a phase III randomized trial.
AB  - BACKGROUND AND PURPOSE: To evaluate the benefits and the drawbacks of post
      operative radiotherapy in completely resected Stage I (a and b) non-small cell
      lung cancer (NSCLC). MATERIALS AND METHODS: Patients with pathological Stages Ia
      and Ib NSCLC have been randomized into two groups: Group 1 (G1) received adjuvant
      radiotherapy, Group 0 (G0) the control group did not receive any adjuvant
      therapy. Local control, toxicity and survival have been evaluated. RESULTS:
      Between July 1989 and June 1997, 104 patients with pathological stage I NSCLC
      have been enrolled in this study. Fifty-one patients were randomized to G1 and 53
      to G0. Six patients have been excluded from the study due to incomplete follow-up
      data. Regarding local control, one patient in the G1 group had a local recurrence
      (2.2%) while in the G0 12 local recurrences have been observed (23%). Seventy-one
      percent of patients are disease-free at 5 years in G1 and 60% in G0 (P=0.039).
      Overall 5-year survival (Kaplan-Meier) showed a positive trend in the treated
      group: 67 versus 58% (P=0.048). Regarding toxicity in G1, six patients
      experienced a grade 1 acute toxicity. Radiological evidence of long-term lung
      toxicity, with no significant impairment of the respiratory function, has been
      detected in 18 of the 19 patients who have been diagnosed as having a post
      radiation lung fibrosis. CONCLUSIONS: Adjuvant radiotherapy gave good results in
      terms of local control in patients with completely resected NSCLC with
      pathological Stage I. Overall 5-year survival and disease-free survival showed a
      promising trend. Treatment-related toxicity is acceptable.

PMID- 11830310
TI  - Conformal radiotherapy for lung cancer: different delineation of the gross tumor
      volume (GTV) by radiologists and radiation oncologists.
AB  - PURPOSE: Delineation of the gross tumor volume (GTV) and organs at risk
      constitutes one of the most important phases of conformal radiotherapy (CRT)
      procedures. In the absence of a clear redefinition of the GTV, for a given
      pathology, complemented by detailed contouring procedures, the GTV are likely to
      be estimated rather arbitrarily with the risk of tumor underdosage or detriment
      to the surrounding healthy tissues. The objective of this study was to compare
      the delineation of the GTV of intrathoracic tumors by radiologists and radiation
      oncologists with experience in the field in various centers. MATERIALS AND
      METHODS: The computed tomography images of ten patients with nonoperated non
      small cell lung cancer (NSCLC) eligible for CRT were reviewed. Nine radiologists
      and eight radiation oncologists working in five different centers, classified as
      either 'junior' or 'senior' according to their professional experience, had to
      delineate the GTV (primary tumor and involved lymph nodes) with predefined
      visualization parameters. A dedicated software was used to compare the delineated
      volumes in terms of intersection and union volumes and to calculate the
      'concordance index' for each patient and each subgroup of physicians. RESULTS:
      Significant differences between physicians and between centers were observed.
      Compared to radiation oncologists, radiologists tended to delineate smaller
      volumes and encountered fewer difficulties to delineate 'difficult' cases. Junior
      physicians, regardless of their specialty, also tended to delineate smaller and
      more homogeneous volumes than senior physicians, especially for 'difficult'
      cases. CONCLUSIONS: Major discordances were observed between the radiation
      oncologists' and the radiologists' delineations, indicating that this step needs
      to be improved. A better training of radiation oncologists in thoracic imaging
      and collaboration between radiation oncologists and radiologists should decrease
      this variability. New imaging techniques (image fusion, positron emission
      tomography, magnetic resonance imaging spectroscopy, etc.) may also provide a
      useful contribution to this difficult delineation.

PMID- 11830311
TI  - Definition of gross tumor volume in lung cancer: inter-observer variability.
AB  - BACKGROUND AND PURPOSE: To determine the inter-observer variation in gross tumor
      volume (GTV) definition in lung cancer, and its clinical relevance. MATERIALS AND
      METHODS: Five clinicians involved in lung cancer were asked to define GTV on the
      planning CT scan of eight patients. Resulting GTVs were compared on the base of
      geometric volume, dimensions and extensions. Judgement of invasion of lymph node
      (LN) regions was evaluated using the ATS/LCSG classification of LN. Clinical
      relevance of the variation was studied through 3D-dosimetry of standard conformal
      plans: volume of critical organs (heart, lungs, esophagus, spinal cord)
      irradiated at toxic doses, 95% isodose volumes of GTVs, normal tissue
      complication probabilities (NTCP) and tumor control probabilities (TCP) were
      compared for evaluation of observer variability. RESULTS: Before evaluation of
      observer variability, critical review of planning CT scan led to up- (two cases)
      and downstaging (one case) of patients as compared to the respective diagnostic
      scans. The defined GTVs showed an inter-observer variation with a ratio up to
      more than 7 between maximum and minimum geometric content. The dimensions of the
      primary tumor had inter-observer ranges of 4.2 (transversal), 7.9 (cranio-caudal)
      and 5.4 (antero-posterior) cm. Extreme extensions of the GTVs (left, right,
      cranial, caudal, anterior and posterior) varied with ranges of 2.8-7.3 cm due to
      inter-observer variation. After common review, only 63% of involved lymph node
      regions were delineated by the clinicians (i.e. 37% are false negative). Twenty
      two percent of drawn in lymph node regions were accepted to be false positive
      after review. In the conformal plans, inter-observer ranges of irradiated normal
      tissue volume were on average 12%, with a maximum of 66%. The probability (in the
      population of all conformal plans) of irradiating at least 95% of the GTV with at
      least 95% of the nominal treatment dose decreased from 96 to 88% when swapping
      the matched GTV with an unmatched one. The average (over all patients) inter
      observer range in NTCP varied from 5% (spinal cord) to 20% (ipsilateral lung),
      whereas the maximal ranges amounted 16% (spinal cord) to 45% (heart). The average
      TCP amounted 51% with an average range of 2% (maximally 5%) in case of matched
      GTVs. These values shifted to 42% (average TCP) with an average range of 14%
      (maximally 31%) when defining unmatched GTVs. Four groups of causes are suggested
      for the large inter-observer variation: (1) problems of methodology; (2)
      impossible differentiation between pathologic structures and tumor; or (3)
      between normal structures and tumor, and (4); lack of knowledge. Only the
      minority of these can be resolved objectively. For most of the causal factors
      agreements have to be made between clinicians, intra- and inter-departmentally.
      Some of the factors will never be unequivocally solved. CONCLUSIONS: GTV
      definition in lung cancer is one of the cornerstones in quality assurance of
      radiotherapy. The large inter-observer variation in GTV definition jeopardizes
      comparison between clinicians, institutes and treatments.

PMID- 11830312
TI  - Radiotherapy treatment planning for patients with non-small cell lung cancer
      using positron emission tomography (PET).
AB  - PURPOSE: Many patients with non-small cell lung cancer (NSCLC) receive external
      beam radiation therapy as part of their treatment. Three-dimensional conformal
      radiation therapy (3DCRT) commonly uses computed tomography (CT) to accurately
      delineate the target lesion and normal tissues. Clinical studies, however,
      indicate that positron emission tomography (PET) has higher sensitivity than CT
      in detecting and staging of mediastinal metastases. Imaging with fluoro-2
      deoxyglucose (FDG) PET in conjunction with CT, therefore, can improve the
      accuracy of lesion definition. In this pilot study, we investigated the potential
      benefits of incorporating PET data into the conventional treatment planning of
      NSCLC. Case-by-case, we prospectively analyzed planning target volume (PTV) and
      lung toxicity changes for a cohort of patients. MATERIALS AND METHODS: We have
      included 11 patients in this study. They were immobilized in the treatment
      position and CT simulation was performed. Following CT simulation, PET scanning
      was performed in the treatment position using the same body cast that was
      produced for CT simulation and treatment. The PTV, along with the gross target
      volume (GTV) and normal organs, was first delineated using the CT data set. The
      CT and PET transmission images were then registered in the treatment planning
      system using either manual or automated methods, leading to consequent
      registration of the CT and emission images. The PTV was then modified using the
      registered PET emission images. The modified PTV is seen simultaneously on both
      CT and PET images, allowing the physician to define the PTV utilizing the
      information from both data sets. Dose-volume histograms (DVHs) for lesion and
      normal organs were generated using both CT-based and PET+CT-based treatment
      plans. RESULTS: For all patients, there was a change in PTV outline based on CT
      images versus CT/PET fused images. In seven out of 11 cases, we found an increase
      in PTV volume (average increase of 19%) to incorporate distant nodal disease.
      Among these patients, the highest normal-tissue complication probability (NTCP)
      for lung was 22% with combined PET/CT plan and 21% with CT-only plan. In other
      four patients PTV was decreased an average of 18%. The reduction of PTV in two of
      these patients was due to excluding atelectasis and trimming the target volume to
      avoid delivering higher radiation doses to nearby spinal cord or heart.
      CONCLUSIONS: The incorporation of PET data improves definition of the primary
      lesion by including positive lymph nodes into the PTV. Thus, the PET data reduces
      the likelihood of geographic misses and hopefully improves the chance of
      achieving local control.

PMID- 11830314
TI  - The modification of human tumour blood flow using pentoxifylline, nicotinamide
      and carbogen.
AB  - AIM: To assess the effect of combining oral nicotinamide, oral pentoxifylline and
      carbogen gas (2% CO2, 98% O2) breathing on human tumour red cell flux. METHODS
      AND MATERIALS: Microregional red blood cell flux was measured in accessible
      tumour nodules using laser Doppler microprobes in 11 patients with histologically
      proven malignancy. Patients received single oral doses of nicotinamide 40 mgkg-1
      and pentoxifylline 1200 mg 2h before a 10-min period of carbogen gas breathing,
      corresponding to peak plasma concentrations of these drugs. Red cell flux in up
      to six microregions in each tumour was measured for 30 min, recording pre-,
      during and post-carbogen breathing for 10 min each. RESULTS: Data from ten of the
      11 patients could be assessed. The red cell flux in 48 microregions was analysed
      and the mean red cell flux was calculated. A mean relative increase in red cell
      flux of 1.18 (+/-0.09, 95% confidence interval (CI)) was observed after 6 min of
      carbogen breathing, 2h after the administration of nicotinamide and
      pentoxifylline. This compares to relative increases of 1.4 (+/-0.39, 95%CI) after
      nicotinamide with carbogen and 1.15 (+/-0.10, 95%CI) after pentoxifylline with
      carbogen. These differences are not statistically significant (P>0.05). The
      increased red cell flux persisted after the cessation of carbogen gas breathing.
      CONCLUSIONS: A combination of pentoxifylline, nicotinamide and carbogen produces
      an increase in human tumour red cell flux, similar to that observed when each of
      the drugs are used alone with carbogen breathing.

PMID- 11830313
TI  - Radiation enhancement by the combined use of topoisomerase I inhibitors, RFS-2000
      or CPT-11, and topoisomerase II inhibitor etoposide in human lung cancer cells.
AB  - BACKGROUND AND PURPOSE: We have tested the camptothecin analogs, RFS-2000 or CPT
      11, in combination with both etoposide and ionizing radiation in vitro to examine
      the radiation enhancing potential of topoisomerase I plus topoisomerase II (Topo
      I+Topo II) inhibition in human cancer cells. MATERIALS AND METHODS: H460 human
      lung carcinoma cells were plated and treated with 10nM RFS-2000 or 4.5microM CPT
      11 for 4h. Cells were then irradiated with various doses and treated with 1microM
      etoposide for 1.5h. Cell survival and sublethal damage recovery (SLDR) were
      determined by clonogenic assay. 7-aminoactinomycin D (7-AAD) staining and flow
      cytometry were used to analyze cell viability/apoptosis after combined treatment
      of drugs with radiation. RESULTS: Survival experiments showed radiation dose
      enhancement ratios (DER) of 1.26, 1.34, and 1.63 for RFS-2000, etoposide, and RFS
      2000 plus etoposide, respectively; the corresponding DER values were 1.30, 1.39,
      and 1.65 for CPT-11, etoposide, and CPT-11 plus etoposide. The analysis of cell
      viability/apoptosis using 7-AAD staining and flow cytometry showed an additive
      effect. Greater inhibition of SLDR was observed with RFS-2000 plus etoposide than
      with either agent separately, but CPT-11 plus etoposide showed a more modest
      effect upon SLDR. CONCLUSIONS: These data show that the combination of Topo I
      inhibitors, RFS-2000 or CPT-11 plus Topo II inhibitor etoposide, is a more
      effective radiation enhancer than either agent alone in human lung cancer cells.
      The mechanism of radiation enhancement may involve inhibition of SLDR with RFS
      2000 plus etoposide, but other mechanisms may be involved in the combined
      treatment including CPT-11.

PMID- 11830315
TI  - Dynamics of tumor oxygenation and red blood cell flux in response to inspiratory
      hyperoxia combined with different levels of inspiratory hypercapnia.
AB  - BACKGROUND AND PURPOSE: Increasing arterial oxygen partial pressure (pO2) by
      breathing hyperoxic gases is an effective means of improving tumor oxygenation,
      although the efficacy of adding CO2 to the inspiratory gas has been discussed
      controversially. This study aimed at analyzing the impact of different
      inspiratory CO2 fractions on the time course of oxygenation and perfusion changes
      in experimental tumors during and after inspiratory hyperoxia. MATERIAL AND
      METHODS: Perfusion and oxygenation of rat DS-sarcomas were studied during
      spontaneous breathing of pure oxygen or hyperoxic gas mixtures containing
      different CO2 fractions (1, 2.5 or 5%). Red blood cell (RBC) flux was assessed as
      a measure of tumor perfusion using the laser Doppler technique and temporal
      changes in mean tumor pO2 were measured polarographically. RESULTS: Mean tumor
      pO2 increased 3.6-fold with pure oxygen, approx. 3.3-fold when 1 or 2.5% CO2 was
      added and 2.7-fold during carbogen breathing. RBC flux also increased by 25-30%
      with all gases. With pure oxygen and with 1% CO2 (+99% O2), perfusion changes
      paralleled those of the mean arterial blood pressure whereas with higher CO2
      fractions, a decrease in resistance to flow was observed. The differences found
      with the various gas mixtures were more pronounced after the end of hyperoxia.
      With pure oxygen, perfusion immediately returned to pretreatment values whereas
      with higher CO2 fractions perfusion remained elevated for at least 30 min.
      CONCLUSIONS: Higher inspiratory CO2 fractions (2.5 or 5%) lead to a prolonged
      improvement of tumor perfusion after the end of inspiratory hyperoxia when
      compared with pure oxygen breathing. Since no principal differences in
      oxygenation and perfusion were seen between the gases containing 2.5 and 5% CO2,
      the former may be preferable for inspiratory hyperoxia.

PMID- 11830316
TI  - Dosimetric verification of modulated photon fields by means of compensators for a
      kernel model.
AB  - The approach in treatment planning of applying beam quality correction factors to
      model compensator-induced depth-hardening effects is investigated and the present
      work comprises a dosimetric verification of the model for a common compensator
      material. Lead sheet modulators for four different phantom shapes were designed
      using a treatment planning system based on the model. The modulators were
      designed to yield homogeneous dose in a plane. The calculated modulation created
      by the lead sheets was re-imported into the treatment planning system and applied
      to a water phantom geometry for verification purposes. Comparing measurements, a
      total of 31 different geometries were measured, with calculations in this
      geometry showing good agreement for depth doses, dose profiles and output data
      with a maximum deviation of 4% except locally in the penumbra region and close to
      the edges of the cut lead sheets.

PMID- 11830318
TI  - Conformality and homogeneity of dose distributions in interstitial implants at
      idealized target volumes: a comparison between the Paris and dose-point optimized
      systems.
AB  - BACKGROUND AND PURPOSE: The use of high dose rate stepping source in interstitial
      brachytherapy provides more possibility to conform the dose distribution to the
      target volume compared to the classical systems. The purpose of this study was to
      evaluate implants made according to the Paris, the stepping source and the
      conformal dosimetry system with respect to dose homogeneity and conformality, and
      to compare these systems using volumetric parameters. MATERIALS AND METHODS:
      Single-plane and double-plane implants with catheters arranged in square and
      triangle pattern were used in the analysis. Twenty-seven idealized planning
      target volumes (PTV) were generated. They formed slabs with rectangular or
      trapezoidal cross-section. The lengths were 3, 5 and 7 cm, the widths and heights
      were determined according to the Paris system for catheter separation of 1, 1.5
      and 2 cm. The dose specification was selected such that the coverage index was
      0.95 for each implant. Optimal active lengths were determined according to the
      best conformality at the optimized implants. From the dose-volume histogram (DVH)
      the following indices were calculated for every implant: conformal (COIN),
      external volume (EI), relative dose homogeneity (HI) and overdose volume (OI).
      Furthermore, the mean central dose (MCD) and minimum target dose (MTD) was also
      determined. The dosimetry systems were compared through the mean values of these
      parameters and the volumetric indices were analyzed according to the geometry of
      the PTV. RESULTS: For the optimized systems the optimal active length was 0.5-1.0
      cm shorter than the target volume length, depending on the catheter separation
      and geometry of the PTV. For the Paris, the stepping source and the conformal
      dosimetry system, the mean COIN was 0.66, 0.82 and 0.82; the mean HI was 0.71,
      0.68 and 0.68; the mean EI was 0.44, 0.17 and 0.17; the mean OI was 0.11, 0.13
      and 0.12, respectively. The statistical analysis showed that the Paris system
      differed from the optimized systems significantly. For the Paris, the stepping
      source and the conformal dosimetry system, the mean reference isodose was 85, 90
      and 95%, the MCD was 100, 100 and 109%, the MTD was 67, 71 and 73%, respectively.
      Regarding geometry of the PTV, the most conformal and homogeneous dose
      distributions occurred when the catheter separation was small, the target volume
      was long and its shape was a thick rectangular slab. CONCLUSIONS: Positioning the
      catheters according to the rules of the Paris system, but applying optimization
      on dose points placed either between the catheters in the whole target volume or
      on the surface of the target volume, and selecting the reference isodose by DVH,
      can provide highly conformal dose distribution to the target volume, with only a
      slightly worsened dose homogeneity compared to the Paris system.

PMID- 11830317
TI  - Quality control of brachytherapy equipment in the Netherlands and Belgium:
      current practice and minimum requirements.
AB  - BACKGROUND AND PURPOSE: Brachytherapy is applied in 39 radiotherapy institutions
      in The Netherlands and Belgium. Each institution has its own quality control (QC)
      programme to ensure safe and accurate dose delivery to the patient. The main goal
      of this work is to gain insight into the current practice of QC of brachytherapy
      in The Netherlands and Belgium and to reduce possible variations in test
      frequencies and tolerances by formulating a set of minimum QC-requirements.
      MATERIALS AND METHODS: An extensive questionnaire about QC of brachytherapy was
      distributed to and completed by the 39 radiotherapy institutions. A separate
      smaller questionnaire was sent to nine institutions performing intracoronary
      brachytherapy. The questions were related to safety systems, physical irradiation
      parameters and total time spent on QC. The results of the questionnaires were
      compared with recommendations given in international brachytherapy QC reports.
      RESULTS: The answers to the questionnaires showed large variations in test
      frequencies and test methods. Furthermore, large variations in time spent on QC
      exist, which is mainly due to differences in QC-philosophy and differences in the
      available resources. CONCLUSIONS: Based on the results of the questionnaires and
      the comparison with the international recommendations, a set of minimum
      requirements for QC of brachytherapy has been formulated. These guidelines will
      be implemented in the radiotherapy institutions in The Netherlands and Belgium.

PMID- 11830319
TI  - Letter to the editor concerning Hurkmans et al., Radiother Oncol 2001;58:105-120.

PMID- 11830322
TI  - Adjuvant and salvage radiation therapy after radical prostatectomy for
      adenocarcinoma of the prostate.

PMID- 11830324
TI  - Lebrec D, Poynard T, Hillon P, Benhamou J-P. Propranolol for prevention of
      recurrent gastrointestinal bleeding in patients with cirrhosis. A controlled
      study [N Engl J Med 1981;305:1371-1374].

PMID- 11830325
TI  - Development of dominant bile duct stenoses in patients with primary sclerosing
      cholangitis treated with ursodeoxycholic acid: outcome after endoscopic
      treatment.
AB  - BACKGROUND/AIMS: Primary sclerosing cholangitis is characterized by progressive
      fibrotic inflammation and obliteration of intra- and/or extrahepatic bile ducts.
      METHODS: In a prospective study of 106 patients treated for up to 13 years with
      ursodeoxycholic acid, the development of major bile duct stenoses and the
      efficacy of endoscopic measures have been evaluated. RESULTS: Of 106 patients ten
      had major duct stenoses at entry, and during a median follow-up period of 5.0
      years another 43 developed a dominant stenosis. Fifty-two patients with dominant
      stenoses were treated endoscopically by repeated balloon dilatations and five
      patients were temporarily stented. Complications of endoscopic procedures were
      pancreatitis (5.2%), bacterial cholangitis (3.3%) and bile duct perforation
      (0.5%). Five years after the first dilatation of a dominant stenosis the Kaplan
      Meier survival rates free of liver transplantation were 100% in stage 2, 72% in
      stage 3 and 50% in stage 4 disease. The actuarial survival free of liver
      transplantation of the whole group at 3, 5 and 7 years were 0.987, 0.935 and
      0.891 and the corresponding survival rates predicted with the Mayo multicenter
      survival model were 0.860, 0.775 and 0.737 (P<0.001). CONCLUSIONS: In advanced
      disease, occlusion of major bile ducts with time occurs in the majority of
      patients. Endoscopic opening of dominant stenoses is effective and appears to be
      a valuable addition to the medical treatment of such patients.

PMID- 11830326
TI  - Decreased microsomal triglyceride transfer protein activity contributes to
      initiation of alcoholic liver steatosis in rats.
AB  - BACKGROUND/AIMS: To elucidate the role of microsomal triglyceride transfer
      protein (MTP) in the pathogenesis of alcoholic fatty liver, the effects of
      ethanol on MTP activity and gene expression were investigated. METHODS AND
      RESULTS: Male Sprague-Dawley rats fed an ethanol-containing liquid diet for 37
      days, respectively, showed 2.9- and 4.9-fold increases in hepatic cholesterol and
      triglyceride content in comparison with rats fed an isocaloric ethanol-free diet
      (P<0.01). Furthermore, a significant decrease in MTP activity and mRNA expression
      (by 27 and 58%, respectively) was observed after ethanol administration.
      Intravenous injection of human recombinant hepatocyte growth factor (hrHGF) on
      each of the last 7 days markedly suppressed ethanol-induced lipid accumulation in
      the liver. This inhibition of fatty change by hrHGF was accompanied by recovery
      of MTP activity and gene expression. No inhibitory effect of hrHGF on ethanol
      induced acyl-CoA synthetase activation was observed. Experiments using human
      hepatoma-derived HepG2 cells indicated a direct positive effect of hrHGF on MTP
      gene expression as well as apolipoprotein B secretion. CONCLUSIONS: These results
      suggest that reduced MTP activity is crucial to development of alcoholic fatty
      liver, while promotion of MTP activity by HGF might serve as a therapeutic
      measure against alcoholic liver steatosis.

PMID- 11830327
TI  - Effects of somatostatin and octreotide on portal-systemic collaterals in portal
      hypertensive rats.
AB  - BACKGROUND/AIMS: Somatostatin and its long-acting analogue, octreotide, have been
      used to cease variceal bleeding with uncertain mechanisms. This study
      investigated whether somatostatin and octreotide have a direct vasoconstrictive
      effect on the portal-systemic collaterals of portal-hypertensive rats and
      potentiate the vasoconstriction induced by endothelin-1 in these vascular beds.
      METHODS: The vascular responses of collateral vessels to graded concentrations of
      somatostatin (10(-9)-10(-5) mol/l), octreotide (10(-10)-10(-6) mol/l),
      norepinephrine (10(-9)-10(-5) mol/l) and vehicle (Krebs solution) were evaluated
      in perfused collateral vascular beds of rats with portal hypertension induced by
      partial portal vein ligation. In addition, the perfusion pressure changes of
      collateral vessels to endothelin-1 (10(-8) mol/l) in the presence of
      vehicle(control), somatostatin (10(-6) mol/l) and octreotide (10(-6) mol/l) were
      tested. RESULTS: Compared with the vehicle group, norepinephrine significantly
      increased the perfusion pressure of collateral vessels at concentrations between
      10(-7) and 10(-5) mol/l. In contrast, neither somatostatin nor octreotide
      significantly changed the perfusion pressure. Somatostatin and octreotide
      significantly enhanced the endothelin-1-induced vasoconstrictive effect on the
      collaterals. CONCLUSIONS: Somatostatin and octreotide exert no direct
      vasoconstrictive effect on the collateral vessels of portal hypertensive rats. In
      the presence of endothelin-1, somatostatin and octreotide exert a local
      vasoconstrictive effect on these vascular beds.

PMID- 11830328
TI  - Hepatocyte growth factor induces collagenase (matrix metalloproteinase-1) via the
      transcription factor Ets-1 in human hepatic stellate cell line.
AB  - BACKGROUND/AIMS: Although hepatocyte growth factor recently has been shown to
      decrease hepatic fibrosis in animal models, the molecular mechanisms of this
      effects remain to be elucidated. We investigated regulation of collagenase
      expression by hepatocyte growth factor in hepatic stellate cells. METHODS: A
      human hepatic stellate cell line, LI90, was treated with hepatocyte growth
      factor. Expression of collagenase, 72 kDa gelatinase, procollagen alpha 1(I),
      tissue inhibitor of matrix metalloproteinase-1, transforming growth factor-beta
      1, or Ets-1, and carboxyterminal telopeptide of type I collagen was examined. Ets
      1 binding activity was determined by gel mobility shift assay, collagenase
      promoter activity was evaluated by reporter gene assay. LI90 cells were also
      transfected with Ets-1 antisense oligonucleotides with or without hepatocyte
      growth factor. RESULTS: Hepatocyte growth factor increased expression of
      collagenase mRNA and protein, and an increase in Ets-1 mRNA preceded the increase
      in collagenase mRNA. Collagenase activity and protein, and a degradation product
      of type I collagen were increased in the medium. Nuclear extracts from treated
      LI90 cells also showed increased Ets-1 binding activity. Hepatocyte growth factor
      and cotransfection of Ets-1 enhanced promoter activity of collagenase gene.
      Furthermore, treatment of LI90 cells with Ets-1 antisense oligonucleotides
      downregulated basal and hepatocyte growth factor-induced Ets-1 and collagenase
      mRNA expression. CONCLUSIONS: Collectively, the results suggest that hepatocyte
      growth factor increases collagenase expression in hepatic stellate cells via the
      Ets-1 transcription factor-dependent manner.

PMID- 11830329
TI  - Rearrangement of the cytoskeletal network induced by platelet-derived growth
      factor in rat hepatic stellate cells: role of different intracellular signalling
      pathways.
AB  - BACKGROUND/AIMS: Cytoskeletal reorganization plays an important role in the
      regulation of different cell functions, such as proliferation and migration.
      Since platelet-derived growth factor (PDGF) stimulates both proliferation and
      chemotaxis of hepatic stellate cells (HSC), we investigated the effects of this
      cytokine on cytoskeletal components of cultured rat HSC. METHODS/RESULTS:
      Exposure of HSC to PDGF induced the formation of stress fibres and of a ruffled
      configuration of the plasma membrane, evaluated by both fluorescence and electron
      microscopy. These modifications were also induced by exposure to the protein
      kinase C (PKC) activator phorbol-12-myristate-13-acetate (PMA) and abolished by
      pretreatment with the PKC inhibitor calphostin C, with the Rho inhibitor C3
      exoenzyme and with the intracellular calcium chelator MAPTAM, but not with the PI
      3 kinase inhibitor wortmannin or with the mitogen-activated protein kinase kinase
      inhibitor PD 98059. PDGF induced a translocation of Rho from the cytosol to the
      membrane which was inhibited by C3 exoenzyme and by calpostin C, and which was
      also induced by PMA. Moreover, PDGF induced a rearrangement of vinculin which was
      prevented by C3 exoenzyme and calphostin C. CONCLUSIONS: PDGF-induced
      cytoskeletal reorganization in HSC is dependent on PKC and Rho, thus suggesting
      that these two pathways may play an important role in the response of liver to
      injury.

PMID- 11830330
TI  - Oncostatin M stimulates tissue inhibitor of metalloproteinase-1 via a MEK
      sensitive mechanism in human myofibroblasts.
AB  - BACKGROUND/AIMS: We previously showed that in cultured human myofibroblasts
      (hMFBs), Oncostatin M (OSM)-stimulated collagen accumulation is associated with
      increased tissue inhibitor of metalloproteinase (TIMP)1 message. However, the
      mechanism is unknown. METHODS: hMFBs were isolated by outgrowth from cirrhotic
      liver explants and cultured. Using OSM (10 ng/ml) stimulation, with and without
      PD98059 (PD, a specific mitogen-activated protein kinase/extracellular signal
      related kinase (MEK) inhibitor), we measured: TIMP-1 protein in culture medium by
      Western blot, TIMP-1 mRNA levels and stability by Northern analysis, TIMP-1
      promoter activity (including transcription site mutation analysis), DNA binding
      activity to nuclear proteins by electrophoretic mobility shift assay (EMSA), and
      total and phosphorylated MAP kinase in hMFB extracts by Western blot. RESULTS:
      OSM stimulation of hMFBs increased TIMP-1 protein production 1.69-fold, TIMP-1
      mRNA levels 2.36-fold, promoter activity 2.22-fold, TIMP-1 message stability, and
      phosphorylation of mitogen-activated protein kinase (MAPK). PD inhibited OSM
      mediated stimulation of TIMP-1 protein, mRNA, promoter activity, phosphorylation
      of MAPK, and TIMP-1 message stability. An SP-1 transcription site of the TIMP-1
      promoter is essential for OSM induction of TIMP-1 promoter activity. EMSA
      demonstrates that this site binds to transcriptional factors SP-1 and SP-3.
      CONCLUSIONS: OSM stimulates the TIMP-1 axis in hMFBs in vitro via a MEK-MAP
      kinase cascade.

PMID- 11830331
TI  - Hepatic stellate cell/myofibroblast subpopulations in fibrotic human and rat
      livers.
AB  - BACKGROUND/AIMS: Hepatic stellate cells (HSC) are commonly considered the
      precursor population of septal myofibroblasts (MF) in cirrhosis. We studied the
      distribution and expression profile of mesenchymal (myo)fibroblast-like
      populations in fibrotic and cirrhotic liver, in an attempt to elucidate their
      possible interrelationships. METHODS: Fibrotic/cirrhotic livers (from 22 human
      explants and from two rat models: carbon tetrachloride intoxication, bile duct
      ligation) were studied by means of immunohistochemistry (single and double
      immunostaining) with antibodies raised against desmin, alpha-smooth muscle actin
      (alpha SMA), glial fibrillary acidic protein (GFAP), neural-cell adhesion
      molecule (N-CAM), synaptophysin, neurotrophins, neurotrophin receptors and alpha
      B-crystallin (ABCRYS). RESULTS: Septal MF showed the same expression profile as
      portal MF, in human and rat, being alpha SMA/ABCRYS/brain-derived nerve growth
      factor/GFAP-expression, with additional N-CAM- and desmin-expression in rat
      portal/septal MF. Perisinusoidally located HSC stained with all tested markers,
      MF at the septal/parenchymal interface showed an expression profile, intermediate
      between the profiles of HSC and portal/septal MF. CONCLUSIONS: In advanced
      fibrosis and in cirrhosis, regardless of cause or species, three distinct
      mesenchymal (myo)fibroblast-like liver cell subpopulations can be discerned:
      portal/septal MF, interface MF and perisinusoidally located HSC. The fact that
      septal MF share more characteristics with portal MF than with HSC might suggest
      descent.

PMID- 11830332
TI  - Early induction of nerve growth factor-induced genes after liver resection
      reperfusion injury.
AB  - BACKGROUND/AIMS: Nur-related factor 1 (Nurr1) has been implicated in liver
      generation after hepatectomy. We hypothesized that the genes in the nerve growth
      factor-induced gene B (NGFI-B) family was induced in liver ischemia-reperfusion
      injury. METHODS: Expression of the NGFI-B family genes was examined by the
      reverse transcription-polymerase chain reaction in rat and human livers. In situ
      hybridization was performed to check the localization of the NGFI-B gene in rat
      liver. Expression of phospho-Ser-133-specific cyclic adenosine-3' :5'
      monophosphate response element binding (pCREB) protein was examined by Western
      blot analysis and gel shift assay, since the promoter region of the NGFI-B family
      genes contains CRE. RESULTS: The expression of the NGFI-B family genes were
      recognized within 30 min after ischemia-reperfusion in rat liver, which was
      augmented by cycloheximide injection. In human specimens, the NGFI-B family genes
      expression was stronger than that before ischemic insult. pCREB protein was
      detected in the rat liver sampled 15 min after reperfusion. Gel shift assay
      suggested that CREB bound to neuron-derived orphan receptor gene in rat liver
      cells. CONCLUSIONS: We recognized the early induction of the NGFI-B family genes
      after ischemia-reperfusion injury in rat and human livers. A pathway via CREB may
      be responsible for the induction.

PMID- 11830333
TI  - Transgenic mice overexpressing human Bcl-2 are resistant to hepatic ischemia and
      reperfusion.
AB  - BACKGROUND/AIMS: Apoptosis is a key mechanism of reperfusion injury in the
      ischemic liver. The apoptotic pathway is highly regulated by anti-apoptotic
      factors, such as Bcl-2. We evaluated the effect of Bcl-2 overexpression on
      apoptosis and the activation of the apoptotic cascade after hepatic ischemia and
      reperfusion. METHODS: Ninety minutes of ischemia and reperfusion was performed in
      Bcl-2 transgenic and non-transgenic mice. Bcl-2 overexpression was determined by
      immunohistochemistry and Western blot. Liver injury was determined by aspartate
      aminotransferase (AST), Tunel test and the activation of the apoptotic cascade
      and animal survival. RESULTS: Bcl-2 overexpression was present in all hepatocytes
      and non-parenchymal liver cells in transgenic mice. Bcl-2 overexpression resulted
      in significant decreased AST levels after ischemic injury, and complete
      inhibition of apoptosis. After 90 min of total hepatic ischemia all control mice
      died, while four transgenic mice survived permanently. Bcl-2 overexpression was
      associated with inhibition of caspase 3 activation after reperfusion and
      increased baseline levels of cytoplasmic cytochrome c, caspase 3, and a reduction
      of Bcl-x(L) production. CONCLUSIONS: Bcl-2 overexpression protects against
      ischemic injury by inhibiting apoptosis. Extensive overproduction of Bcl-2 is
      associated with a compensatory increase of baseline levels of cytoplasmic
      cytochrome c and caspase 3, and a deletion of Bcl-x(L).

PMID- 11830334
TI  - Protective effect of Linomide on TNF-alpha-induced hepatic injury.
AB  - BACKGROUND/AIMS: Linomide is an immunomodulator that ameliorates several
      autoimmune and inflammatory diseases. We assessed the effect of Linomide on
      microvascular perfusion failure, leukocyte recruitment and hepatocellular injury
      induced by tumor necrosis factor alpha (TNF-alpha) and D-Galactosamine (Gal).
      METHODS: After 3 days of Linomide pretreatment (1, 10 and 100 mg/kg/day), rats
      were challenged with TNF-alpha/Gal for 24 h. Microvascular perfusion, leukocyte
      endothelium interactions in hepatic postsinusoidal venules and leukocyte
      sequestration in sinusoids were evaluated using intravital microscopy. Liver
      enzymes were measured spectrophotometrically. RESULTS: Challenge with TNF
      alpha/Gal significantly reduced sinusoidal perfusion, and increased leukocyte
      rolling, adhesion and liver enzymes. Interestingly, pretreatment with Linomide
      (10 and 100 mg/kg/day) significantly reduced TNF-alpha/Gal-induced leukocyte
      rolling by 65 and 63%, and leukocyte adhesion by 87 and 84%, respectively.
      Moreover, Linomide (10 and 100 mg/kg/day) decreased sinusoidal sequestration of
      leukocytes by 71 and 51%, and markedly improved sinusoidal perfusion. Moreover,
      Linomide reduced aspartate aminotransferase by 87-97%, and alanine
      aminotransferase by 79-96%. However, Linomide had no protective effect when
      administered concomitantly with TNF-alpha/Gal. CONCLUSIONS: These data
      demonstrate a dose-dependent inhibitory effect of Linomide on perfusion failure,
      leukocyte recruitment and hepatocellular injury provoked by TNF-alpha. Indeed,
      these findings suggest that Linomide may be an effective substance for protection
      of the liver in sepsis.

PMID- 11830335
TI  - The histone-deacetylase inhibitor Trichostatin A blocks proliferation and
      triggers apoptotic programs in hepatoma cells.
AB  - BACKGROUND/AIMS: Effective treatment for hepatocellular carcinoma is urgently
      needed. The histone-deacetylase inhibitor Trichostatin A (TSA) was shown to
      induce apoptosis in non-hepatic cells at submicromolar concentrations. However,
      the effect of TSA on hepatoma cells is unknown. METHODS: The hepatoma cells
      HepG2, MH1C1, Hepa1-6 and Hep1B as well as human fibroblasts (control cells) were
      exposed to TSA (10(-6) to 10(-9)M). Cell proliferation was assessed by measuring
      DNA-synthesis and cell numbers. Apoptosis was quantified by flow cytometry and by
      the TdT-mediated dUTP nick-end labeling method. Expression patterns of cell cycle
      and/or apoptosis-associated p27, p21(cip/waf), bax, bcl-2, cyclin A and (pro)
      caspase 3 were studied using quantitative Western blotting. Activation of caspase
      3 was analyzed via a colorimetric assay. RESULTS: 10(-6)M TSA inhibited DNA
      synthesis by 46% (HepG2) to 64% (MH1C1) after 24h, inducing a G(2)/M-phase arrest
      and apoptosis. TSA increased activation of caspase 3 and expression of cyclin A,
      p2l(cip/waf), bax and (pro)-caspase 3, while bcl-2 was downregulated. Human
      fibroblasts remained unaffected. CONCLUSIONS: TSA inhibits hepatoma cell growth
      in vitro, which are otherwise particularly resistant to chemotherapy. Its anti
      proliferative activity is paralleled by a comparable rate of apoptosis. TSA may
      be a promising agent for treatment of hepatocellular carcinoma in vivo.

PMID- 11830336
TI  - Cyclosporin A pretreatment in a rat model of warm ischaemia/reperfusion injury.
AB  - BACKGROUND/AIMS: These studies investigated the role of apoptosis following
      ischaemia/reperfusion (I/R) injury to the liver and the effect of pretreatment
      with Cyclosporin A. METHODS: Male Sprague-Dawley rats received 30 min of warm
      ischaemia followed by a period of reperfusion of 6 h. Rats were given olive oil
      or Cyclosporin A (30 mg/kg p.o.) the day before surgery. Neutrophil numbers were
      assessed in haematoxylin-eosin-stained sections of liver. In situ staining of
      sections using TdT-mediated dUTP-fluorescein nick-end labelling was carried out
      to determine the extent of apoptosis, followed by electron microscopy. Semi
      quantitative polymerase chain reaction (PCR) analysis of the transcript for Fas
      antigen was performed. RESULTS AND CONCLUSIONS: High levels of apoptosis were
      observed in I/R injury, which were greatly ameliorated in Cyclosporin A
      pretreated groups. PCR analysis indicated a reduction in the level of expression
      of Fas transcript in Cyclosporin A-treated rats. Histological analysis showed a
      significant increase in the number of neutrophils infiltrating I/R-injured tissue
      (62 +/- 10.69, n=16), which was markedly reduced by Cyclosporin A pretreatment
      (16 +/- 7, n=6, P<0.05). These results indicate a role of parenchymal apoptosis
      in the pathogenesis of I/R injury, which occurs in association with neutrophil
      infiltration, both of which can be significantly reduced by Cyclosporin A
      pretreatment.

PMID- 11830337
TI  - Intra-familial transmission of hepatitis B virus in Italy: phylogenetic sequence
      analysis and amino-acid variation of the core gene.
AB  - BACKGROUND/AIMS: Transmission of hepatitis B virus (HBV) in countries of
      intermediate endemicity, such as Italy, is thought to be primarily horizontal
      and, to a lesser extent, vertical. Most chronic carriers therefore become
      infected in infancy or at a very young age. The index cases in such events have
      been assumed to come from within the family unit or from sources outside the
      immediate family, with whom the affected person is in close contact. METHODS: We
      studied a number of Italian families with multiple members chronically infected
      with HBV. The precore/core region of the virus was amplified from serum derived
      HBV-DNA, and the sequences subjected to phylogenetic tree analysis. In addition,
      the extent of amino-acid variation within the core region was correlated to HLA
      type, determined by allele-specific PCR. RESULTS: The phylogenetic tree analysis
      provided strong evidence of intra-familial transmission of the virus. Analysis of
      amino-acid substitutions in the core region in relation to HLA class II alleles
      from members of the same family showed that these substitutions were restricted
      in siblings with concordant, and more diverse in those with discordant HLA
      haplotypes. CONCLUSIONS: This is consistent with major histocompatibility complex
      class II mediated selection pressure on the virus.

PMID- 11830338
TI  - Hepatitis C virus (HCV) E1 and E2 protein regions that specifically bind to HepG2
      cells.
AB  - BACKGROUND/AIMS: Identify hepatitis C virus (HCV) sequences in E1 and E2 protein
      binding to HepG2. METHODS: Synthetic 20-mer long, ten-residue overlapped
      peptides, from E1 and E2 proteins, were tested in HepG2 or Raji cell-binding
      assays. Affinity constants, binding site number per cell and Hill coefficients
      were determined by saturation assay for high activity binding peptides (HABPs).
      Receptors for HepG2 cell were determined by cross-linking and sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis analysis. RESULTS: Twelve HABPs were
      found in HCV genotype 1a, allowing six hepatocyte-binding sequences (HBSs) to be
      defined: two peptide-binding regions in E1 HABPs 4913 (YQVRNSTGLYHVTNDCPNSS) and
      4918 (MTPTVATRDGKLPATQLRRHY). Four hepatocyte-binding regions were defined in E2:
      region-I, peptide 4931 (ETHVTGGSAGHTVSGFVSLLY); region-II, 4937-4939
      (HHKFNSSGCPERLASCRPLTDFDQGWGPISYANGSGPDQR); region-III, 4943-4945
      (PVYCFTPSPVVVGTTDRSGAPTYSWGENDTDVFVLNNTR) and region-IV, 4949-4952
      (CGAPPCVIGGAGNNTLHCPTDCFRKHPDATYSRCGSGPWITPRCLVDYPY). The underlined sequences
      are most relevant in the binding process. HABPs 4913 and 4938 also bind to CD81
      positive Raji cells. Region-II 4938 HABPs bind to 50 and 60kDa HepG2 cell
      membrane surface proteins. CONCLUSIONS: Six HVRs to the HepG2 were identified.
      Some HABPs have been previously found to be antigenic and immunogenic. HABPs,
      4918 (from E1), 4938, 4949, 4950, 4951 and 4952 (from E2) have not been
      previously recognised. These HABPs could be relevant to HCV invasion of
      hepatocytes.

PMID- 11830339
TI  - Outcome of anti-HBe positive chronic hepatitis B in alpha-interferon treated and
      untreated patients: a long term cohort study.
AB  - BACKGROUND/AIMS: We studied the influence of biochemical and virologic patterns
      and interferon on the outcome of anti-HBe positive chronic hepatitis B in 164
      (103 treated) consecutive patients, followed-up prospectively for a mean of 6
      years (21 months-12 years). METHODS: Histology, biochemical and virologic
      profiles were characterized by monthly monitoring during the first 12 months of
      follow-up. Thereafter patients underwent blood and clinical controls every 4 and
      6 months, respectively. Cirrhosis at follow-up histology or end stage
      complications of cirrhosis served as end points for the analysis of factors
      influencing disease progression in patients with baseline chronic hepatitis or
      cirrhosis, respectively. RESULTS: Disease progression was associated with older
      age (P<0.001), absence of previous HBeAg history (P=0.017) and higher serum HBV
      DNA levels (P=0.009) (more frequently observed in unremitting disease profile,
      P=0.012) at multivariate analysis. Fluctuations of IgM anti-HBc levels
      (associated with disease exacerbations, P=0.045) correlated with end stage
      complications in cirrhotics (P=0.011). Disease improved in 14.6 and 1.6% of
      treated and untreated patients, respectively (P=0.015): interferon slowed disease
      progression (P<0.001). CONCLUSIONS: The outcome of anti-HBe positive chronic
      hepatitis B is worsened by older age and persistent viral replication or
      hepatitis exacerbations in chronic hepatitis or in cirrhotic patients,
      respectively. Interferon reduces by 2.5-folds disease progression.

PMID- 11830340
TI  - Polymorphisms in the interleukin-10, tumor necrosis factor-alpha, and
      transforming growth factor-beta1 genes in chronic hepatitis C patients treated
      with interferon and ribavirin.
AB  - BACKGROUND/AIMS: In hepatitis C infection, the production of inappropriate
      cytokine levels appears to contribute to viral persistence and to affect the
      response to antiviral therapy. Additionally, polymorphisms in the cytokine genes
      may affect the production of the cytokines. In this study, we determined the
      frequency of the genotypes associated with polymorphisms of the interleukin-10
      and tumor necrosis factor-alpha gene promoters, and transforming growth factor
      beta 1 gene leader sequence, and investigated their association with clinical
      features and the response to interferon-alpha and ribavirin therapy in chronic
      hepatitis C infection. METHODS: Genomic DNA from 80 patients and 37 racially
      matched healthy controls was studied by polymerase chain reaction and direct
      automated sequencing. RESULTS: The interleukin-10 -1082 G/G genotype was
      identified more frequently in patients than in controls (P=0.048). The
      transforming-growth factor-beta 1 +29 (codon 10) C/C genotype was associated with
      resistance to the therapy (P=0.029). After adjusting for potential confounding
      variables, patients exhibiting the C/C genotype were less likely to respond to
      treatment than patients with the T/T or T/C genotypes. CONCLUSIONS: These results
      suggest that inheritance of the interleukin-10 -1082 G/G and the transforming
      growth factor-beta 1 +29 C/C genotypes, which appear to affect the cytokine
      production, may be associated with susceptibility to chronic hepatitis C
      infection and resistance to combined antiviral therapy.

PMID- 11830341
TI  - Endoscopic treatment for primary sclerosing cholangitis?

PMID- 11830342
TI  - Interferon alpha therapy in HBeAg-negative chronic hepatitis B: new data in
      support of long-term efficacy.

PMID- 11830343
TI  - Antiretroviral drug toxicity -- a challenge for the hepatologist?

PMID- 11830344
TI  - Acute liver failure associated with antiretroviral treatment for HIV: a report of
      six cases.
AB  - BACKGROUND/AIMS: Severe hepatotoxicity is a rare but potentially fatal side
      effect of all antiretrovirals. We report a series of six human immunodeficiency
      virus (HIV)-infected patients admitted with acute liver failure (ALF) over a 25
      month period, of whom five died. All had been treated with a range of
      antiretroviral therapy and only two had had acquired immune deficiency syndrome
      (AIDS) defining illnesses. RESULTS: Median duration of antiretroviral therapy was
      12.5 months (range 1-23). Median time from the introduction of new antiretroviral
      therapy to the onset of ALF was 8 weeks (range 2-12). The development of ALF was
      unrelated to duration of HIV treatment or type of antiretroviral therapy, and was
      not predicted by close out-patient supervision and monitoring of liver function.
      Biochemical investigations were variable but revealed a predominantly
      hepatocellular pattern. Liver biopsy revealed typical features of mitochondrial
      toxicity in only one case, with confluent hepatocellular necrosis, inflammation
      and cholestasis seen in the others. CONCLUSIONS: There is a need to increase
      awareness of the potential hepatotoxicity of antiretroviral therapy and to
      develop means of predicting its development. With increasing usage of
      antiretroviral therapy, severe hepatotoxicity and ALF may arise more frequently,
      and the outcome is poor despite intensive supportive therapy.

PMID- 11830345
TI  - Hepatic artery aneurysm within focal nodular hyperplasia.

PMID- 11830346
TI  - Hepatitis B viral genotypes and lamivudine resistance.

PMID- 11830347
TI  - Persistence of YMDD variants after withdrawal of Lamivudine.

PMID- 11830351
TI  - The biochemistry of aging muscle.
AB  - Between the ages of 20 and 80, humans lose approximately 20-30% of their skeletal
      muscle mass. This age-related loss of muscle mass, sometimes described as
      'sarcopenia of old age', is the consequence of complicated multifactorial
      processes and is commonly associated with osteopenia or osteoporosis.
      Consequences of the aging changes in muscle are declining physiological function
      and loss of muscle strength, typically associated with reduced physical
      activities. Consequently, falls and subsequent serious injuries are prevalent in
      the elderly. Thus, it is imperative to try and understand the processes, leading
      to age-related muscle loss, in order to develop means to retard this phenomenon
      leading to improved quality of life in the elderly. It is possible to divide the
      causes of muscle aging to intrinsic factors, involving changes at the molecular
      and cellular levels, and to extrinsic or environmental factors. The purpose of
      this review is to describe some of the biochemical processes and the possible
      mechanisms of muscle aging and to evaluate the importance of various extrinsic
      factors such as nutrition, exercise and limb immobilization. Changes in the aging
      skeletal muscle are reviewed with regard to: (a) enzyme activities, protein
      turnover and repair capacities (b) mitochondrial functioning and energy reserve
      systems (c) ion content and regulation (d) oxidative stress and free radicals (e)
      nutrition and caloric restriction (f) exercise and limb immobilization.

PMID- 11830352
TI  - Roles of the Werner syndrome protein in pathways required for maintenance of
      genome stability.
AB  - Werners syndrome is a disease of premature aging where the patients appear much
      older than their chronological age. The gene codes for a protein that is a
      helicase and an exonuclease, and recently we have learned about some of its
      protein interactions. These interactions are being discussed as they shed light
      on the molecular pathways in which Werner protein participates. Insight into
      these pathways brings insight into the aging process.

PMID- 11830353
TI  - A mortality cost of virginity at older ages in female Mediterranean fruit flies.
AB  - Mortality rates were measured over the lifetime of 65,000 female Mediterranean
      fruit flies, Ceratitis capitata, maintained in either all-female (virgin) cages
      or cages with equal initial numbers of males, to determine the effect of sexual
      activity and mating on the mortality trajectory of females at older ages.
      Although a greater fraction of females maintained in all-female (virgin) cages
      survived to older ages, the life expectancy of the surviving virgins was less
      than the life expectancy of surviving non-virgins at older ages. This was due to
      a mortality crossover where virgin flies experience lower mortality than mated
      flies from eclosion to Day 20 but higher mortality thereafter. These results
      suggest that there are two consequences of mating--a short-term mortality
      increase (cost) and a longer term mortality decrease (benefit).

PMID- 11830354
TI  - Telomere shortening with aging in human thyroid and parathyroid tissue.
AB  - Progressive telomere shortening with aging was studied using normal thyroid
      tissue specimens from 46 human subjects aged between 0 and 98 yr and normal
      parathyroid tissue specimens from 21 human subjects aged between 0 and 83 yrs.
      There has hitherto been no information documented about telomere length in such
      thyroid and parathyroid tissues. Age-related shortening at rates of 91 and 92
      base pairs (bp) per year, respectively, were observed. Telomere lengths of normal
      thyroid tissues were 16.53 +/- 1.10 (mean +/- SE), 14.31 +/- 0.80, 11.27 +/- 0.68
      and 8.73 +/- 1.08 kbp for age groups less than 2, 20-50, 51-80 and more than 80
      yr. Telomere lengths of normal parathyroid tissues were 15.80 +/- 1.46 (mean +/-
      SE), 15.36 +/- 0.86 and 10.93 +/- 0.78 kbp for age groups less than 4, 20-50 and
      51-80 yr. Telomere shortening occurred after 50 yr of age in thyroid and
      parathyroid tissues. Human thyroid and parathyroid tissues do not seem to show
      the rapid reduction in telomere length early in life that was reported for some
      human cell types, suggesting that the rate of telomere shortening has tissue
      specific characteristics.

PMID- 11830356
TI  - Age-related changes in the calcium homeostasis of adherent neutrophils.
AB  - The elderly are susceptible to infections and show a decline in neutrophil (PMN)
      functions that are regulated by cytosolic calcium [Ca2+]i. This study measures
      [Ca2+]i in suspended and adherent PMN of young and elderly individuals by using
      flow cytometry, confocal microscopy, the bacterial peptide fMLP, and the
      fluorescent Ca2+ indicator fluor-3/acettoxymethyl ester. PMN from both age groups
      show a steep and transient fMLP-induced Ca2+ increase. This increase is
      independent of external divalent cations and is desensitized by a subsequent
      exposure to the same agonist. Adherent PMN of the elderly express elevated
      [Ca2+]i before (basal) and after fMLP activation but show reduced ability to
      mobilize Ca2+ into and from the cytosol. PMN of the elderly take longer (13.7 +/-
      3 s) to attain the maximal response compared to those of young adults (5.7 +/-
      0.8 s). PMN from both age groups show heterogeneity in the time and magnitude of
      this response. However, PMN of the elderly show a decrease in the proportion of
      cells with prompt and effective reaction and an increase in the representation of
      a cell subpopulation manifesting delayed response. We conclude that age-related
      delayed and reduced PMN response to a bacterial peptide could hamper functional
      activities that are essential in host protection against infections.

PMID- 11830355
TI  - Telomere lengths are characteristic in each human individual.
AB  - BACKGROUND: A great deal of attention has been focused on telomeres in relation
      to cellular aging, immortality, and cancer. However, there is no simple link
      between telomeres and tissue turnover. We recently proposed a hypothesis that
      telomere shortening with aging and telomere lengths in different organs are
      characteristic for human individuals. METHODS: To test this, telomere lengths
      were measured using DNA from cerebral cortex, myocardium, liver, renal cortex and
      spleen tissues obtained from human subjects ranging in age from neonates to
      centenarians. RESULTS: Regression analyses demonstrated telomere reduction rates
      of 29-60 base pair (bp) per year in the liver, renal cortex and spleen, but no
      such decrease in the cerebral cortex and myocardium. Significant correlation was
      found between tissues within individuals, such as cerebral cortex versus (vs)
      myocardium, cerebral cortex vs liver, cerebral cortex vs renal cortex, myocardium
      vs liver, myocardium vs renal cortex, and liver vs renal cortex. In most cases,
      the longest telomeres were observed in the myocardium and the shortest in the
      liver or renal cortex. CONCLUSIONS: Telomere lengths did not show clear
      correlation with tissue renewal times in vivo, but rather were characteristic for
      individuals.

PMID- 11830357
TI  - Differential modulation of phospholipase D and phosphatidate phosphohydrolase
      during aging in rat cerebral cortex synaptosomes.
AB  - Phosphatidylcholine (PC) hydrolysis generates two important second messengers:
      phosphatidic acid (PA) and diacylglycerol (DAG). Phospholipase D (PLD) and
      phosphatidate phosphohydrolase (PAPase) are involved in their generation and
      therefore are key enzymes in signal transduction. Specific isoforms of these
      enzymes are activated by receptor occupancy in brain. Phosphatidylinositol 4,5
      bisphosphate-dependent PLD (PIP2-PLD) and N-ethylmaleimide-insensitive PAPase
      (PAP2) have been suggested to act in series to generate the biologically active
      lipids PA and DAG. In the present study we examine age-induced changes mainly in
      PIP2-PLD and PAP2 activities in cerebrocortical synaptosomes from adult (4
      months) and aged (28 months) Wistar rats. Aging increases the activity of both
      enzymes. Guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS) and cytosol (from
      cerebral cortex) stimulate PLD activity in adult and senescent synaptosomal
      membranes, the effect being greater in the latter. Under the same experimental
      conditions PAP2 activity was stimulated in aged membranes whereas in adult
      membranes GTPgammaS had no effect and cytosol showed a slight inhibitory effect.
      Diacylglycerol lipase (DGL) activity differs from that of PAP2 in aged rats and
      it was 21% inhibited with respect to synaptosomal membranes from adult rats.
      Increased sinaptosomal PLD activity in aged membranes appears to be independent
      of G protein regulation, whereas PAP2 activity is differentially regulated by
      GTPgammaS in aged membranes with respect to adult membranes. Our results suggest
      that under G-protein activation conditions, DAG production by the serial
      activation of PLD and PAP2 activities is increased in synaptosomal membranes from
      aged brain. The present paper demonstrates that PA generation (PLD activity) and
      degradation (PAPase activity) are differentially modulated during the aging
      process.

PMID- 11830358
TI  - Enhancement of bone defect healing in old rats by TGF-beta and IGF-1.
AB  - Bone defects are often created in order to repair bone pathologies. In the aging
      population, the healing of such defects is very limited. Bone healing in aging
      depends on the availability of various hormone and growth factors. The ability of
      growth factors to enhance bone formation in femoral defects in old rats was
      tested. Bone defects were induced in femurs of old rats. A single dose of
      transforming growth factor-beta (TGF-beta), IGF-1, TGF-beta+IGF-1 or saline was
      inserted in the defect and bones were tested after 2 and 4 weeks. Radiology
      revealed that mineralization appeared in the 2 weeks group in defects treated
      with TGF-beta and in defects treated with TGF-beta, TGF-beta+IGF-1 in the 4 weeks
      groups. Computerized tomography (CT) coronal and axial images revealed that 4
      weeks after treatment with TGF-beta+IGF-1, a complete bone bridge was observed.
      Morphology revealed that these defects were filled with trabecular bone. A less
      pronounced bone healing was observed after TGF-beta or IGF-1, while control
      specimens revealed partial healing of the bone defect. Biomechanical tests
      indicated that treatment with TGF-beta, IGF-1 or TGF-beta+IGF-1 resulted in a
      significant increase of bone bending rigidity compared to control in the 4 weeks
      group and that TGF-beta+IGF-1 was the most inductive in this respect. The ability
      to induce bone healing in aging by TGF-beta+IGF-1 is of a great clinical
      importance for restoration of bone strength and biomechanical properties of bone
      defects in aging.

PMID- 11830359
TI  - Longevity minimalists: life table studies of two species of northern Michigan
      adult mayflies.
AB  - Life table studies were conducted on both sexes of newly emerged subimagoes of
      the mayfly species, Hexagenia limbata (n = 4472) and Ephemera simulans (n =
      1254), which have two- and one-year life cycles, respectively. The expectation of
      life at emergence for H. limbata was approximately 2.6 days for both sexes with
      the last individual (a female) dying on day 8. Expectation of life for E.
      simulans was 1.6 and 2.0 days for males and females, respectively, with the last
      individuals (both sexes) dying on day 3. The results reveal that mortality does
      not occur in one large step in this group of rapidly senescing organisms. Rather
      deaths are spread over several days when the adult mayflies are maintained under
      laboratory conditions.

PMID- 11830361
TI  - Effects of early spatial training on water maze performance: a longitudinal study
      in mice.
AB  - The aim of the present study is to establish whether in mice the effects of an
      early experience in the Morris water maze are maintained after a long period. A
      longitudinal study was performed in which mice of two different strains (NMRI and
      C57) received spatial training at 2 months of age and their performance was re
      evaluated 8 and 16 months later. In both strains, results showed a beneficial
      effect of prior experience on this spatial memory task even 8 months after the
      initial training. At 18 months of age, performance of C57 mice that were trained
      at 2 months of age for the first time was similar to those who received their
      first training at 10 months of age. These findings suggest that the beneficial
      effect of previous training could be limited by time. In addition, water maze
      performance of 18 month-old C57 mice did not differ from their earlier
      performance when they were 10 months of age, which would indicate that experience
      in this task could prevent some of the age-related spatial learning deficits
      observed in mice.

PMID- 11830360
TI  - The effect of 1,2,4-thiotriazolyl 5-mercaptoacetic acid new derivatives on lipid
      peroxidation in the heart from adult and old rats during stress.
AB  - The effect of 3-(4-pyridyl)-1,2,4-thiotriazolyl 5-mercaptoacetic acid kalium salt
      (Rumosol) and 3-(4-pyridyl)-1,2,4-thiotriazolyl 5-mercaptoacetic acid
      morpholinium salt (drug 2) on the concentration of Schiff base in myocardium of
      adult (10-12 months) and old (22-25 months) Wistar rats during immobilized stress
      were investigated. Here we show that the accumulation of Schiff base in the heart
      from both age groups was inhibited after injection of derivatives of 1,2,4
      thiotriazolyl 5-mercaptoacetic acid prior to immobilization. Drug 2 possessed a
      two-fold higher pronounced capacity against Rumosol to inhibit the accumulation
      of Schiff base in the heart during stress. In myocardium from old rats, drug 2
      decreased more effectively the stress-induced stimulation of lipid peroxidation
      as compared to dimethyl sulfoxide.

PMID- 11830362
TI  - Gene transcript profiling in aging research.
AB  - Advances in biotechnology have led to methods for quantifying the relative
      concentrations of thousands of mRNAs in parallel. While these are powerful
      methods that can be used for both hypothesis testing and hypothesis generation,
      gene transcript profiling has some limitations as a tool to study aging. These
      include the difficulty in separating effects of aging from analytical and
      biological variability, statistical problems associated with simultaneous
      determination of so many different gene transcripts, and uncertainty about the
      functional significance of changes in mRNA concentrations. In this review, these
      issues are discussed with a focus on two methods for profiling mRNAs--serial
      analysis of gene expression (SAGE) and DNA arrays.

PMID- 11830363
TI  - In situ detection of reactive oxygen species and nitric oxide production in
      normal and pathological tissues: improvement by differential interference
      contrast.
AB  - Reactive oxygen species (ROS), among which nitric oxide (NO) is currently
      included, play a plethora of (patho)physiological roles. Harman's free radical
      theory of aging put forth over 40 years ago received full support since then. A
      nitric oxide hypothesis of aging recently proposed by McCann, is very likely to
      be the object of widespread investigation in the near future. Therefore, the
      possibility of localizing at the (sub)cellular level under the light microscope
      the sites of ROS and NO production with simple and reliable methods appears as a
      powerful tool for analytic cytology and pathology. Various histochemical methods
      were developed for visualizing ROS production; a recently improved version to
      localize superoxide (and possibly also singlet oxygen), based on a DAB-Mn2+ -Co2+
      reaction, appears very promising. Since the direct detection of NO is still very
      difficult, the action sites of NO are currently localized by the identification
      of NO synthase (NOS). The most widespread method to reveal the catalytic activity
      of NOS is that of demonstrating the fixation-resistant NADPH diaphorase activity
      with the tetrazolium salt method. We have improved this method by using a
      tetrazolium salt whose formazan particles are very thin and lipid insoluble
      (tetranitroblue tetrazolium, TNBT) and by including a tissue protectant,
      polyvinyl alcohol, in the incubation medium. Here significant examples of
      application of the DAB-Mn2+ -Co2+ technique for ROS and the TNBT-PVA method for
      NOS to normal liver and brain and to solid tumors are presented. We further
      document the usefulness of Nomarkis's differential interference contrast (DIC) to
      analyze wide tissue areas where ROS production or NOS activity is low or even
      nil. The improved version for NOS allowed for the first time to demonstrate NOS
      activity in liver fat-storing cells and in astrocyte-like cells in the brain.

PMID- 11830366
TI  - An interactive framework for an analysis of ECG signals.
AB  - In this study, we introduce and discuss a development of a highly interactive and
      user-friendly environment for an ECG signal analysis. The underlying neural
      architecture being a crux of this environment comes in the form of a self
      organizing map. This map helps discover a structure in a set of ECG patterns and
      visualize a topology of the data. The role of the designer is to choose from some
      already visualized regions of the self-organizing map characterized by a
      significant level of data homogeneity and substantial difference from other
      regions. In the sequel, the regions are described by means of information
      granules-fuzzy sets that are essential in the characterization of the main
      relationships existing in the ECG data. The study introduces an original method
      of constructing membership functions that incorporates class membership as an
      important factor affecting changes in membership grades. The study includes a
      comprehensive descriptive modeling of highly dimensional ECG data.

PMID- 11830364
TI  - Aging, the brain and human prion disease.
AB  - Human prion diseases (PrD) preferentially manifest in the elderly. Their
      neuropathology may coexist with tau immunoreactive neuropil threads,
      neurofibrillary tangles, and beta-amyloid senile plaques, most likely
      representing an age-related change rather than a pathogenic link with Alzheimer's
      disease. Cerebrovascular disease with brain infarction, another malady preferring
      the elderly, is useful to prove the origin of PrD-associated prion protein
      deposition exclusively from neurons.

PMID- 11830367
TI  - Fuzzy detection of EEG alpha without amplitude thresholding.
AB  - Intelligent automated systems are needed to assist the tedious visual analysis of
      polygraphic recordings. Most systems need detection of different
      electroencephalogram (EEG) waveforms. The problem in automated detection of alpha
      activity is the large inter-individual variability of its amplitude and duration.
      In this work, a fuzzy reasoning based method for the detection of alpha activity
      was designed and tested using a total of 32 recordings from seven different
      subjects. Intelligence of the method was distributed to features extracted and
      the way they were combined. The ranges of the fuzzy rules were determined based
      on feature statistics. The advantage of the detector is that no alpha amplitude
      threshold needs to be selected. The performance of the alpha detector was
      assessed with receiver operating characteristic (ROC) curves. When the true
      positive rate was 94.2%, the false positive rate was 9.2%, which indicates good
      performance in sleep EEG analysis.

PMID- 11830368
TI  - Automatic detection of distorted plethysmogram pulses in neonates and paediatric
      patients using an adaptive-network-based fuzzy inference system.
AB  - Despite the fact that pulse oximetry has become an essential technology in
      respiratory monitoring of neonates and paediatric patients, it is still fraught
      with artefacts causing false alarms resulting from patient or probe movement. As
      the shape of the plethysmogram has always been considered as a useful visual
      indicator for determining the reliability of SaO(2) numerical readings,
      automation of this observation might benefit health care providers at the
      bedside. We observed that the systolic upstroke time (t(1)), the diastolic time
      (t(2)) and heart rate (HR) extracted from the plethysmogram pulse constitute
      features, which can be used for detecting normal and distorted plethysmogram
      pulses. We developed a technique for classifying plethysmogram pulses into two
      categories: valid and artefact via implementations of fuzzy inference systems
      (FIS), which were tuned using an adaptive-network-based fuzzy inference system
      (ANFIS) and receiver operating characteristics (ROC) curves analysis. Features
      extracted from a total of 22,497 pulse waveforms obtained from 13 patients were
      used to systematically optimise the FIS. A further 2843 waveforms obtained from
      another eight patients were used for testing the system, and visually classified
      into 1635 (58%) valid and 1208 (42%) distorted segments. For the optimum system,
      the area under the ROC curve was 0.92. The system was able to classify 1418 (87%)
      valid segments and 897 (74%) distorted segments correctly. The calculations of
      the system's performance showed 87% sensitivity, 81% accuracy and 74%
      specificity. In comparison with the 95% confidence interval (CI) thresholding
      method, the fuzzy system showed higher specificity (P=0.008,P<0.01), and no
      significant difference was found between the two methods in terms of sensitivity
      (P=0.720,P>0.05) and accuracy (P=0.053,P>0.05). We therefore conclude that the
      algorithm used in this system has some potential in detecting valid and distorted
      plethysmogram pulse. However, further evaluation is needed using larger patient
      groups.

PMID- 11830369
TI  - An ischemia detection method based on artificial neural networks.
AB  - An automated technique was developed for the detection of ischemic episodes in
      long duration electrocardiographic (ECG) recordings that employs an artificial
      neural network. In order to train the network for beat classification, a cardiac
      beat dataset was constructed based on recordings from the European Society of
      Cardiology (ESC) ST-T database. The network was trained using a Bayesian
      regularisation method. The raw ECG signal containing the ST segment and the T
      wave of each beat were the inputs to the beat classification system and the
      output was the classification of the beat. The input to the network was produced
      through a principal component analysis (PCA) to achieve dimensionality reduction.
      The network performance in beat classification was tested on the cardiac beat
      database providing 90% sensitivity (Se) and 90% specificity (Sp). The neural beat
      classifier is integrated in a four-stage procedure for ischemic episode
      detection. The whole system was evaluated on the ESC ST-T database. When
      aggregate gross statistics was used the Se was 90% and the positive predictive
      accuracy (PPA) 89%. When aggregate average statistics was used the Se became 86%
      and the PPA 87%. These results are better than other reported.

PMID- 11830370
TI  - Bounded-depth threshold circuits for computer-assisted CT image classification.
AB  - We present a stochastic algorithm that computes threshold circuits designed to
      discriminate between two classes of computed tomography (CT) images. The
      algorithm employs a partition of training examples into several classes according
      to the average grey scale value of images. For each class, a sub-circuit is
      computed, where the first layer of the sub-circuit is calculated by a new
      combination of the Perceptron algorithm with a special type of simulated
      annealing. The algorithm is evaluated for the case of liver tissue
      classification. A depth-five threshold circuit (with pre-processing: depth-seven)
      is calculated from 400 positive (abnormal findings) and 400 negative (normal
      liver tissue) examples. The examples are of size n=14,161 (119 x 119) with an 8
      bit grey scale. On test sets of 100 positive and 100 negative examples (all
      different from the learning set) we obtain a correct classification close to 99%.
      The total sequential run-time to compute a depth-five circuit is about 75h up to
      230h on a SUN Ultra 5/360 workstation, depending on the width of the threshold
      circuit at depth-three. In our computational experiments, the depth-five circuits
      were calculated from three simultaneous runs for depth-four circuits. The
      classification of a single image is performed within a few seconds.

PMID- 11830373
TI  - Patellar tendon length--the factor in patellar instability?
AB  - Patellar tendon length has been compared in 42 knees with a history of patellar
      dislocation, and 51 control knees. A lateral X-ray and a magnetic resonance image
      (MRI) were taken of each knee. The mean radiological patellar tendon length was
      46 mm in the controls and 53 mm in the dislocation group. From MRI images, the
      mean was 44 mm in controls and 52 mm in the dislocation group. This means that
      the patellar tendon is significantly (P<0.0001) longer in patients with a history
      of patellar dislocation on both MRI and X-ray. There is no significant difference
      (P=0.52) between X-ray and MRI measurements of tendon length. The distance
      between the tibial plateau and the point of tendon insertion was also measured
      and found to be 28 and 29 mm in the control and dislocation groups, respectively.
      There is no significant difference between these two measures (P=0.19). In
      conclusion, patella alta is caused by a long patellar tendon rather than a low
      insertion into the tibia. Measuring the length of the patellar tendon using MRI
      is more specific and more sensitive than the Caton-Deschamps index for patellar
      instability.

PMID- 11830374
TI  - Natural progression of osteo-chondral defect in the femoral condyle.
AB  - We have tried to establish the course of an isolated osteochondral defect in a
      femoral condyle would take if it were not treated surgically. We studied 15 knees
      in 12 patients where a diagnosis of the condition had been made in the past and
      no surgical treatment instituted for it. Each patient was examined clinically and
      had an MRI scan. The average period of follow-up was 109 months, the range being
      54-282 months. Six patients (seven knees) were under the age of 18 at the onset
      of symptoms. Of these, MRI of six knees showed either no abnormality or a healed
      lesion. Where the onset was after skeletal maturity, six of the eight knees
      showed features osteoarthritis on the MRI scan. Symptomatically, there was also a
      difference between the two groups.

PMID- 11830376
TI  - Open wedge tibial osteotomy: combined coronal and sagittal correction.
AB  - A theoretical mathematical study of coronal and sagittal correction during upper
      tibial osteotomy is proposed. The amount of opening to be made in the coronal and
      sagittal planes is quantified with the help of tables. The precision of the
      correction is not limited by the method itself but rather by the clinical and
      radiological determination of the pre-operative deformity as well as the
      precision of the surgical technique.

PMID- 11830375
TI  - Fixation strength of meniscal repair devices.
AB  - The aim of this study was to measure and compare the ultimate failure strengths
      and cyclic fatigue strengths of currently available meniscal suturing devices. No
      statistically significant difference in failure load was found between a vertical
      loop suture (mean 46.3 N), a horizontal mattress suture (52.5 N), the T-fix
      Device (47.5 N), and the 16-mm (39.2 N) and 13-mm (32.8 N) Bionix Arrow.
      Statistically inferior results were seen with the 10-mm Bionix Arrow (18.8 N),
      the S.D. Sorb Stapler (4.3 N), and the 12-mm Arthrex Meniscal Dart (10.5 N)
      (P<0.01). The Mitek Meniscal Repair System (28.1 N) performed intermediate, with
      significantly better results than the S.D. Sorb Stapler and the 12-mm Arthrex
      Dart, but significantly worse than the vertical and horizontal sutures, the T-fix
      and Bionix 16-mm Device (P<0.01). Cyclic fatigue strength was significantly less
      for the 10-mm Bionix Arrow, the S.D. Sorb Stapler, and the 12-mm Arthrex Meniscal
      Dart (P<0.01) compared to all other devices. We conclude that the 13- and 16-mm
      Bionix Arrow and the T-fix Device have comparable ultimate failure strengths and
      cyclic fatigue strengths to conventional meniscal suturing techniques. The 10-mm
      Bionix Arrow, S.D. Sorb Stapler, and the 12-mm Arthrex Meniscal Dart, however,
      have far inferior failure and cyclic fatigue strengths and their clinical
      application should be questioned.

PMID- 11830377
TI  - Early healing processes of free tendon grafts within bone tunnels is bone
      specific: a morphological study in a rabbit model.
AB  - In order to function as effective ligament replacements, free tendon grafts must
      become firmly healed into bone tunnels as soon as possible. We hypothesized that
      graft incorporation would be bone-specific. Free semitendinosus tendon grafts
      were inserted into drill holes in a lapine medial collateral ligament
      reconstruction model; thus, creating tibial and femoral bone-specific
      incorporation sites. Femur-semitendinosus tendon-tibia complexes were harvested
      from 26 rabbits for histological analysis at various healing times: 0, 6, 12, or
      24 weeks post-surgery. Incorporation and remodeling of the graft in the chondral
      callus was much more extensive at the cancellous-filled femoral insertion than
      within the marrow-dominated tibial insertion, suggesting that tendon graft
      healing may depend on the cancellous bone architecture at the graft site.

PMID- 11830378
TI  - Treatment of patello-femoral arthritis using the Lubinus patello-femoral
      arthroplasty: a retrospective review.
AB  - There are few published results in the literature on patello-femoral
      arthroplasty. The aim of this study was to help to define the place of patello
      femoral arthroplasty in the treatment of isolated patello-femoral arthritis. All
      patients who underwent patello-femoral arthroplasty using the Lubinus prosthesis
      for patello-femoral arthritis between 1992 and 1998 in two neighbouring district
      general hospitals were studied. There were 34 patients who underwent 45
      arthroplasties. The modified Hungerford and Kenna scoring system and the Insall
      and Crosby scoring system were used to clinically evaluate the patients. Serial
      radiographs were assessed for patellar malalignment, mechanical failure and
      progressive arthritic change. Twenty-three knees (64%) had a good or excellent
      result, six (17%) had an unsatisfactory result and seven (19%) were revised to
      either a total knee arthroplasty (5 knees) or patellofemoral arthroplasty (2
      knees). Although the results do not compare favourably with those of total knee
      replacement for generalised arthritis of the knee; we believe that with careful
      patient selection coupled with careful surgical technique, patello-femoral
      arthroplasty can be successfully used to treat isolated patello-femoral
      osteoarthritis.

PMID- 11830379
TI  - The effect of torsion on the appearance of the rupture surface of the ACL of
      rabbits.
AB  - This study investigates how torsion affects the mechanical properties and
      appearance of the rupture surfaces of the anterior cruciate ligament (ACL).
      Rupture of the ACL is frequent among athletes and twisting of the knee during
      rupture is often implicated as a major factor in the injury. The problem is
      compounded by the ACL having limited ability to heal when ruptured. Thirty-two
      specimens were stretched to failure at tension--torsion rates of 10 mm/min and 1
      degree/s, 10 mm/min and 40 degree/s, 500 mm/min and 1 degree/s and 500 mm/min and
      40 degree/s. Results from these experiments were compared with those from pure
      tension tests performed at displacement rates of 10 and 500 mm/min. The changes
      that occurred during the rupture process were monitored by video recordings and
      the appearance of the rupture surfaces studied by scanning electron microscopy
      (SEM). We found significant differences in stiffness between tests carried out
      with and without torsion. The macro and microscopic appearance of the ruptures
      from specimens tested with torsion at different displacement rates were similar
      although, for the slow displacement rate, the rupture surfaces were different
      from those from tests carried out without torsion. The failure modes for all
      tests carried with torsion were similar, with all the specimens failing in the
      ligament substance by fibre pullout. The modes of failure for tests carried at
      500 mm/min with torsion were different from those tested without torsion. Half of
      the specimens tested without torsion failed by tibial avulsion, whereas all
      specimens tested with torsion failed in the ligament substance. These results
      suggest that torsion affects both mechanical and structural properties of the ACL
      and should, therefore, be considered when designing or selecting replacements for
      the ACL.

PMID- 11830380
TI  - Differences in three intercondylar notch geometry indices between males and
      females: a cadaver study.
AB  - The primary purpose of this unique evaluation of cadaveric skeletal geometry was
      to compare intercondylar notch geometry between males and females. One hundred
      male skeletons and 100 female skeletons were evaluated. Three indices of notch
      geometry were calculated from digital photographs of the distal femur: notch
      width index, notch area index, and notch shape index. Notch shape index for males
      exceeded that for females (P<0.004). The intercondylar notch appears less round
      in females and may play a role in causing ACL injuries. Future studies are
      required to confirm any link between notch geometry and ACL injury.

PMID- 11830381
TI  - Main functional roles of knee flexors/extensors in able-bodied gait using
      principal component analysis (I).
AB  - This study was undertaken to demonstrate how principal component analysis (PCA)
      can be used to detect the main functional structure of actions taken by knee
      flexors/extensors during able-bodied gait. PCA was applied as a classification
      and curve structure detection method for knee sagittal muscle moment developed
      during walking of 20 young, healthy male subjects. Over 90% of the information
      provided by the first three principal components (PCs) was chosen for further
      biomechanical interpretation. PCA was able to identify the three main functional
      contributions of knee sagittal muscle moment during able-bodied gait, namely
      control balance, foot clearance/limb preparation and shock absorption.

PMID- 11830382
TI  - Knee flexors/extensors in gait of elderly and young able-bodied men (II).
AB  - In this study the fundamental tasks of muscle activity at the knee during gait in
      elderly and young able-bodied subjects were identified using principal component
      analysis (PCA). Role discrepancies between the older and younger subjects for the
      actions executed by the knee flexors and extensors during the gait cycle were
      also investigated. The t-test for independent groups was applied to determine
      significant differences between spatio-temporal and peak muscle moment parameters
      (P<0.05). PCA as a multivariate classification and curve structure detection
      method was applied to the sagittal knee muscle moment curves of twenty elderly
      (72 +/-5.5 years) and twenty young (25 +/- 8.1 years) subjects. The first three
      principal components (PCs) which accounted for 80% (older) and 93% (younger) of
      the information were retained for further analysis. Providing stable locomotion
      was recognised as a major task of the knee in the older subjects, while for the
      younger subjects the knee contributed to both balance and propulsion. Supporting
      the body during single limb support should be considered the only common task at
      the knee level in elderly and young subjects' gait. The lack of muscle power for
      propulsion might be the reason for not identifying the knee extensor muscle roles
      in the first three major tasks during elderly gait. Functional asymmetry can be
      considered the result of a different ordering of the functional roles of the
      muscles acting at the knee level in elderly and young subjects.

PMID- 11830383
TI  - Defining the femoral axis on lateral knee fluoroscopy.
AB  - The methodological detail about determining the femoral axis on lateral
      fluoroscopic images of the knee is lacking. This paper reports on the use of the
      posterior border of the lower femoral diaphysis to represent the axis. This
      method is accurate, simple, reliable and can be used by researchers studying knee
      joint kinematics using dynamic video fluoroscopy. It is also useful in the
      outpatient clinic to assess the flexion/extension position of femoral components
      after knee arthroplasty.

PMID- 11830384
TI  - Meniscal arrow migration into the popliteal fossa following attempted meniscal
      repair: a report of two cases.

PMID- 11830388
TI  - [Looking for unity].

PMID- 11830385
TI  - Tibial cyst formation after anterior cruciate ligament reconstruction using a new
      bioabsorbable screw.
AB  - We report a case of tibial cyst formation twelve months after anterior cruciate
      ligament reconstruction using hamstring graft. A composite bioabsorbable
      interference screw made of 'beta tricalcium phosphate and poly L-lactide' fixed
      the graft distally. The patient presented with acute symptoms of pain and
      swelling over the proximal tibia. Curettage of the cyst resulted in complete
      recovery within 3 months.

PMID- 11830389
TI  - [Some proposals drawn from lessons learned from quality control results in
      clinical biochemistry].

PMID- 11830390
TI  - [Neonatal screening for cystic fibrosis: a new screening program and a new
      challenge].

PMID- 11830391
TI  - [Biochemical diagnosis of pheochromocytoma and neuroblastomas].
AB  - Pheochromocytoma and neuroblastoma are distinct tumours, but their biological
      diagnosis is based on secretion increase of one or several catecholamines. Assays
      have to be very sensible and specific for an early diagnosis. 24 hours urinary
      catecholamines and metabolites are currently measured, but technical improvements
      permit plasma metanephrine assay, an excellent indicator of pheochromocytoma.
      HPLC coupled to electrochemical detection represents the most efficient
      methodology. After a review of urinary and plasma assay methods, the authors show
      usual values of catecholamines, metanephrines, HVA and VMA, according to ages,
      and give examples of results encountered in classical or not tumours and in
      falsely positive cases. Urinary metanephrine assay is the most sensible and
      specific in biological diagnosis of pheochromocytoma, while catecholamines and
      VMA assays lack of sensibility. Results have to be given by 24 hours and by
      creatinine ratio. Metanephrine assay can be performed also in plasma and exhibits
      the same interest. However, in urine as in plasma, in case of renal failure,
      results cannot be interpreted. Neuroblastoma biological diagnosis is based
      classically on HVA, VMA, and dopamine assays, nowadays only in 24 hours urine (or
      in urinary micturition for screening), and results are also expressed as
      creatinine ratio. But even if several assays are advisable, 5% of the
      neuroblastoma cases do not produce increased catecholamine values. In some cases,
      metanephrine assay could be of interest. After the age of 12 months, clinical
      expression of neuroblastoma is dramatic in 70% of cases. So, a biological
      screening has been experimented in several countries including France. A French
      translation of the consensus conference report (1998) is appended, which shows
      the complexity of neuroblastoma screening. Now, there is no evidence that early
      tumour detection by screening lessens the mortality rate, but a weak benefit is
      not excluded.

PMID- 11830392
TI  - [Environmental chemical pollution and toxic risk for humans: the particular role
      of organochlorine pesticides].
AB  - There is an increasing concern about environmental exposure to multiple chemicals
      and adverse changes in reproductive development, function, or behaviour in
      wildlife. The major group of environmental chemicals, such as organochlorine
      pesticides, polychlorinated biphenyls (PCBs) and other xenoestrogens are
      currently known to have estrogenic effects in vertebrates or fishes. Recent
      studies suggest that past exposure to such estrogenic compounds may affects the
      risk of developing breast cancer, precocious puberty, or impaired fertility in
      man.

PMID- 11830393
TI  - [Evaluation of the Beckman Coulter HmX hematology analyser at a general
      hospital].
AB  - The Beckman Coulter HmX is an hematological analyzer designed to provide a
      complete hematological profile including CBC, WBC differential (diff) and
      reticulocyte parameters. It has been evaluated in our laboratory over a two weeks
      period with three purposes: (1) a technical evaluation of the HmX performance, in
      regard to repeatability, linearity, carry over; (2) a comparison of numerical
      results (CBC, WBC diff) and analytical performance (flag sensitivity and
      specificity) with those obtained with the Coulter MaxM in use in our laboratory;
      (3) an analysis of the flagging algorithms using the blood smear as the reference
      method. The first part of the evaluation showed that the Beckman Coulter HmX is
      reproducible, and linear. The comparison between MaxM and HmX showed that the
      results given by the two instruments are similar and suggested that the Beckman
      Coulter HmX could replace the current hematology analyzer in use in our
      laboratory. The comparison of the flag system performance, between the Beckman
      Coulter HmX and the Coulter MaxM, has been performed with samples from three
      subgroups of patients (general departments, surgery and intensive care,
      hematological unit), and showed that the HmX is significantly more sensitive than
      the MaxM, with an higher global efficiency. The comparison of predictive values
      also showed a better performance of the HmX. In conclusion, the Beckman Coulter
      HmX is suited for an use in medium sized hospital laboratories (80 to 150 CBC
      diff/day), with good technical and analytical performance, a throughput of 75
      samples/hr and a workstation allowing data management in accord with quality
      assurance guidelines in France.

PMID- 11830394
TI  - [Interference of hydroxocobalamine treatment on commun biochemical
      determinations].
AB  - Hydroxocobalamin, antidote of the cyanide poisoning, is a red and water soluble
      pigment, which colors biological mediums. The interferences caused by this
      molecule are studied for plasma pools overloaded with hydroxocobalamin for
      concentrations from 0 to 1,125 mg.L-1. The results of 16 biochemical parameters
      on Vitros  750 XRC (Ortho-clinical Diagnostics) and of 23 biochemical parameters
      on Cobas  Integra 700 (Roche Diagnostics) are examined. With this analytical
      system, unconjugated and conjugated bilirubin, creatinin, and CK results are
      changed as soon as plasma concentration of hydroxocobalamin reachs 124 mg.L-1.
      For the Vitros  750 XRC, ASAT, iron, creatinin, phosphorus are more sensitive to
      this interference. But, other results are changed for the two analytical systems
      for superior hydroxocobalamin concentrations.

PMID- 11830395
TI  - [Relevance of the new test Access Toxo IgM (II) in the serological interpretation
      of toxoplasmosis in pregnancy].
AB  - The detection of specific IgM is an important element in the diagnosis of
      seroconversion. In this study, we compared the new test   Access  Toxo IgM (II)  
      versus the previous test   Access  Toxo IgM   (I). This comparative study was
      done with 507 random sera and 89 selected sera (seroconversion, residual IgM, non
      specific IgM). The sensitivity and the specificity are higher with the new test
      (100% & 100% versus 97% & 98,6% respectively). Then, the high sensitivity of
      Access  Toxo IgM (II) is more convenient for the earlier diagnosis of primary
      Toxoplasma infection. Moreover, the Access  Toxo IgM (II) test was evaluated with
      our first results in routine laboratory (11,000 serology results between June
      2000 and June 2001). With these results, we can confirm the specificity of the
      new test, and also determine the relevance of anti-toxoplasmic IgM. Moreover, an
      increase of sensitivity leads to an increase of residual IgM detection: 64%
      (37/58) of positive IgM is residual (> 4 months) as compared to 35% (27/78) with
      the previous test. In these case, the initiation of other tests such as the
      avidity test is necessary to validate or invalidate a seroconversion during
      pregnancy.

PMID- 11830396
TI  - [Apolipoprotein E polymorphism in a Moroccan population: allele frequency and
      relation to plasma lipid concentrations].
AB  - To date, no data are available on relationship between apolipoprotein E (apo E)
      polymorphism and lipid levels in Moroccan population. The present work reports an
      apo E polymorphism repartition in Moroccan population and relationship between
      this polymorphism and the levels of plasma cholesterol, triglycerides, apo A1, B
      and E. Blood samples from 168 healthy Moroccan individuals from Rabat area (90
      men and 78 women), aged from 20 to 50 years (32   9 years), were analysed for
      serum apo E, A1 and B, triglycerides, and total cholesterol. In parallel,
      genotyping by means of polymerase chain reaction (PCR) and restriction fragment
      length polymorphism (RFLP) was performed. The apo E allelic frequencies were 11%
      for epsilon4, 84% for epsilon3 and 5% for epsilon2. There were correlation
      between apo E alleles and serum lipid concentrations, E2/E3 carriers had
      significantly higher level of apo E than E3/E3, and E4/E3 carriers had
      significantly higher total cholesterol apo B and triglycerides than E3/E3 and
      E2/E3 carriers. The total cholesterol and apo B concentrations are significantly
      higher in women than in men but the triglycerides are lower. The apo A1
      concentration is independent of both sex and apo E genotype. Thus, the results
      demonstrate an influence of apo E alleles on serum cholesterol, triglycerides,
      apo E and apo B concentrations among healthy Moroccan.

PMID- 11830397
TI  - [Comparative evaluation of a latex agglutination test, two Elisa tests and a
      Western blot test for the serodiagnosis of human trichinellosis].
AB  - Serology is a helpful test for the diagnosis of human trichinellosis because
      clinical signs of this disease (fever and myalgias) are non specific. A lot of
      techniques have been studied but very few are commercialized and have been
      comparatively evaluated. We report here the performances of 4 commercially
      available kits: two Elisa tests, one western blot test & one latex agglutination
      test. The specificity and sensitivity of the different tests were assayed on 60
      sera from patients with a proven trichinellosis and on 70 controls. The four
      tests had a 100% sensitivity. The specificity was of 98.6% for the western blot,
      of 93% for the latex agglutination test and of 87 & 77% for the two Elisa tests.
      Cross reactions are mainly observed in patients with other helminthic infections.

PMID- 11830399
TI  - [Plasma cell leukemia: aggressive form of multiple myeloma].

PMID- 11830398
TI  - [Initial leukemic phase of ALK+ anaplastic large T-cell lymphoma, small cell
      variant].

PMID- 11830401
TI  - [Lipoprotein (a) and acute phase inflammation proteins in homozygous sickle cell
      disease].

PMID- 11830402
TI  - [Multivariate control of analytical processes].

PMID- 11830400
TI  - [Solid tumor in terminal phase: interpretation of biologic anomalies (hematologic
      tests)].

PMID- 11830403
TI  - [Internal quality audit questionnaire in the LABM of health facilities].

PMID- 11830404
TI  - Aging in Pacific Northwest forests: a selection of recent research.
AB  - This paper provides an overview of the work reported at a symposium on age
      related changes in the structure and function of forests in the United States
      Pacific Northwest. Some of the work presented at this meeting is reported in the
      peer-reviewed papers comprising this journal issue. Age-related changes in leaf
      structure, CO2 assimilation rate, stable carbon isotope ratio, nitrogen
      concentration and stomatal limitation were demonstrated at many organizational
      scales. At larger scales, age-related changes were reported in canopy structure
      and light profile, stand productivity, tree mortality and respiration. These data
      raise new questions about the potential interaction among the structural and
      functional changes in aging forests, and indicate many avenues for future
      research concerning tree growth and ecosystem functioning.

PMID- 11830405
TI  - Successional changes in live and dead wood carbon stores: implications for net
      ecosystem productivity.
AB  - If forests are to be used in CO2 mitigation projects, it is essential to
      understand and quantify the impacts of disturbance on net ecosystem productivity
      (NEP; i.e., the change in ecosystem carbon (C) storage with time). We examined
      the influence of live tree and coarse woody debris (CWD) on NEP during secondary
      succession based on data collected along a 500-year chronosequence on the Wind
      River Ranger District, Washington. We developed a simple statistical model of
      live and dead wood accumulation and decomposition to predict changes in the woody
      component of NEP, which we call NEP(w). The transition from negative to positive
      NEP(w), for a series of scenarios in which none to all wood was left after
      disturbance, occurred between 0 and 57 years after disturbance. The timing of
      this transition decreased as live-tree growth rates increased, and increased as
      CWD left after disturbance increased. Maximum and minimum NEP(w) for all
      scenarios were 3.9 and -14.1 Mg C ha-1 year-1, respectively. Maximum live and
      total wood C stores of 319 and 393 Mg C ha(-1), respectively, were reached
      approximately 200 years after disturbance. Decomposition rates (k) of CWD ranged
      between 0.013 and 0.043 year-1 for individual stands. Regenerating stands took 41
      years to attain a mean live wood mass equivalent to the mean mass of CWD left
      behind after logging, 40 years to equal the mean CWD mass in 500-year-old forest,
      and more than 150 years to equal the mean total live and dead wood in an old
      growth stand. At a rotation age of 80 years, regenerating stands stored
      approximately half the wood C of the remaining nearby old-growth forests
      (predominant age 500 years), indicating that conversion of old-growth forests to
      younger managed forests results in a significant net release of C to the
      atmosphere.

PMID- 11830406
TI  - Age- and position-related changes in hydraulic versus mechanical dysfunction of
      xylem: inferring the design criteria for Douglas-fir wood structure.
AB  - We do not know why trees exhibit changes in wood characteristics as a function of
      cambial age. In part, the answer may lie in the existence of a tradeoff between
      hydraulic properties and mechanical support. In conifers, longitudinal tracheids
      represent 92% of the cells comprising the wood and are involved in both water
      transport and mechanical support. We used three hydraulic parameters to estimate
      hydraulic safety factors at several vertical and radial locations in the trunk
      and branches: vulnerability to cavitation; variation in xylem water potential
      (psi); and xylem relative water content. The hydraulic safety factors for 12 and
      88 percent loss of conductivity (S(H12) and S(H88), representing the hydraulic
      safety factors for the air entry point and full embolism point, respectively)
      were determined. We also estimated the mechanical safety factor for maximum tree
      height and for buckling. We estimated the dimensionless hydraulic and mechanical
      safety factors for six seedlings (4 years old), six saplings (10 years old) and
      six mature trees (> 110 years old) of Douglas-fir (Pseudotsuga menziesii (Mirb.)
      Franco). Over the natural range of psi, S(H12) decreased linearly from treetop to
      a minimum of 0.95 at the tree base. Young and mature trees had S(H12) values 1.4
      and 1.3 times higher, respectively, at their tips (juvenile wood) than at their
      bases (mature wood). Modeling analyses indicated that if trees were made entirely
      of mature wood, S(H12) at the stem base would be only 0.7. The mechanical safety
      factor was 1.2 times higher for the base of the tree than for the rest of the
      tree. The minimum mechanical safety factor-1.6 for the critical buckling height
      and 2.2 for the critical buckling load-occurred at the base of the live crown.
      Modeling analysis indicated that if trees were made only of mature wood, these
      values would increase to 1.7 and 2.3, respectively. Hydraulic safety factors had
      values that were less than half those for mechanical safety factors, suggesting
      that wood structure in Douglas-fir has evolved primarily as a result of selection
      for hydraulic safety rather than mechanical safety. The results suggest that
      forest managers must consider the role of juvenile wood in tree physiology to
      avoid producing plantations vulnerable to drought.

PMID- 11830407
TI  - Respiratory potential in sapwood of old versus young ponderosa pine trees in the
      Pacific Northwest.
AB  - Our primary objective was to present and test a new technique for in vitro
      estimation of respiration of cores taken from old trees to determine respiratory
      trends in sapwood. Our secondary objective was to quantify effects of tree age
      and stem position on respiratory potential (rate of CO2 production of woody
      tissue under standardized laboratory conditions). We extracted cores from one to
      four vertical positions in boles of +200-, +50- and +15-year-old Pinus ponderosa
      Dougl. ex Laws. trees. Cores were divided into five segments corresponding to
      radial depths of inner bark; outer, middle and inner sapwood; and heartwood. Data
      suggested that core segment CO2 production was an indicator of its respiratory
      activity, and that potential artifacts caused by wounding and extraction were
      minimal. On a dry mass basis, respiratory potential of inner bark was 3-15 times
      greater than that of sapwood at all heights for all ages (P < 0.0001). Within
      sapwood at all heights and in all ages of trees, outer sapwood had a 30-60%
      higher respiratory potential than middle or inner sapwood (P < 0.005). Heartwood
      had only 2-10% of the respiratory potential of outer sapwood. For all ages of
      trees, sapwood rings produced in the same calendar year released over 50% more
      CO2 at treetops than at bases (P < 0.0001). When scaled to the whole-tree level
      on a sapwood volume basis, sapwood of younger trees had higher respiratory
      potential than sapwood of older trees. In contrast, the trend was reversed when
      using the outer-bark surface area of stems as a basis for comparing respiratory
      potential. The differences observed in respiratory potential calculated on a core
      dry mass, sapwood volume, or outer-bark surface area basis clearly demonstrate
      that the resulting trends within and among trees are determined by the way in
      which the data are expressed. Although these data are based on core segments
      rather than in vivo measurements, we conclude that the relative differences are
      probably valid even if the absolute differences are not.

PMID- 11830408
TI  - Photosynthetic differences between saplings and adult trees: an integration of
      field results by meta-analysis.
AB  - Ontogenetic changes in gas exchange parameters provide both insight into
      mechanisms underlying tree growth patterns, and data necessary to scale
      environmental impacts on young trees to predict responses of older trees. We
      present a quantitative review and meta-analysis of field measurements of gas
      exchange parameters in saplings and mature trees of 35 tree species (seven
      conifers, seven temperate deciduous trees, and 21 tropical evergreen trees). Data
      for saplings were obtained in both understory environments and open areas or
      large gaps. We also present data on ontogenetic changes in photosynthesis for
      Pseudotsuga menziesii (Mirb.) Franco and Tsuga heterophylla (Raf.) Sarg., species
      of particular interest because of their large maximal heights and long life
      spans. Among tree species, there is evidence for both ontogenetic increases and
      ontogenetic decreases in photosynthetic capacity on a leaf area basis (A(area)).
      Overall, A(area) is generally higher for upper-canopy leaves of adult trees than
      for saplings, especially in temperate deciduous trees. However, the pattern for
      photosynthetic capacity on a leaf mass basis (A(mass)) is the reverse of that
      observed for A(area). Saplings of both conifers and broad-leaved trees, even when
      acclimated to low-light conditions, characteristically have a higher A(mass) than
      adult trees. This pattern is driven largely by an ontogenetic increase in leaf
      mass per unit area (LMA), as found in 100% of studies reviewed. Data for Pacific
      Northwest conifers, although including measurements on some of the tallest trees
      studied, did not differ greatly from patterns found in other tree species. We
      conclude that ontogenetic changes in LMA are the single most consistent
      difference between saplings and adult trees, and that changes in LMA and related
      aspects of leaf morphology may be critical to understanding both variation in gas
      exchange during tree growth, and stage-dependent responses of trees to
      environmental change.

PMID- 11830409
TI  - Needle anatomy changes with increasing tree age in Douglas-fir.
AB  - Morphological differences between old-growth trees and saplings of Douglas-fir
      (Pseudotsuga menziesii (Mirb.) Franco) may extend to differences in needle
      anatomy. We used microscopy with image analysis to compare and quantify
      anatomical parameters in cross sections of previous-year needles of old-growth
      Douglas-fir trees and saplings at the Wind River Canopy Crane site in Washington
      and at three sites in the Cascade Mountains of Oregon. We also compared needle
      anatomy across a chronosequence of 10-, 20-, 40- and 450-year-old Douglas-fir
      trees from the Wind River site. Anatomy differed significantly between needles of
      old-growth trees and saplings at all sites, suggesting a developmental change in
      needle anatomy with increasing tree age. Compared with needles of old-growth
      trees, needles of saplings were longer and had proportionately smaller vascular
      cylinders, larger resin canals and few hypodermal cells. Astrosclereids, which
      sequester lignin in their secondary cell walls and occupy space otherwise filled
      by photosynthetic cells, were scarce in needles of saplings but abundant in
      needles of old-growth trees. Needles of old-growth trees had an average of 11%
      less photosynthetic mesophyll area than needles of saplings. The percentage of
      non-photosynthetic area in needles increased significantly with increasing tree
      age from the chronosequence of 10-, 20-, 40- and 450-year-old trees at the Wind
      River site. This reduction in photosynthetic area may contribute to decreased
      growth rates in old trees.

PMID- 11830410
TI  - Response of old-growth conifers to reduction in stand density in western Oregon
      forests.
AB  - The positive growth response of healthy young trees to density reduction is well
      known. In contrast, large old trees are usually thought to be intrinsically
      limited in their ability to respond to increased growing space; therefore,
      density reduction is seldom used in stands of old-growth trees. We tested the
      null hypothesis that old-growth trees are incapable of responding with increased
      growth following density reduction. The diameter growth response of 271 Douglas
      fir (Pseudotsuga menziesii (Mirb.) Franco), ponderosa pine (Pinus ponderosa
      Dougl. ex Laws) and sugar pine (Pinus lambertiana Dougl.) trees ranging in age
      from 158 to 650 years was examined 20 to 50 years after density reduction.
      Density reduction involved either light thinning with removal of less vigorous
      trees, or shelterwood treatments in which overstory trees were not removed.
      Ratios of basal area growth after treatment to basal area growth before
      treatment, and several other measures of growth, all indicated that the old trees
      sometimes benefited and were not harmed by density reduction. Growth increased by
      10% or more for 68% of the trees in treated stands, and nearly 30% of trees
      increased growth by over 50%. This growth response persisted for at least 20
      years. During this 20-year period, only three trees in treated stands (1.5%)
      exhibited a rapid decrease in growth, whereas growth decreased in 64% of trees in
      untreated stands. The length of time before a growth response to density
      reduction occurred varied from 5 to 25 years, with the greatest growth response
      often occurring 20 to 25 years after treatment. These results have important
      implications both for the basic biology of aging in woody plants as well as for
      silvicultural practices in forests with old-growth trees.

PMID- 11830411
TI  - Canopy light transmittance in Douglas-fir--western hemlock stands.
AB  - We measured vertical and horizontal variation in canopy transmittance of
      photosynthetically active radiation in five Pseudotsuga menziesii (Mirb.) Franco
      Tsuga heterophylla (Raf.) Sarg. (Douglas-fir-western hemlock) stands in the
      central Cascades of southern Washington to determine how stand structure and age
      affect the forest light environment. The shape of the mean transmittance profile
      was related to stand height, but height of mean maximum transmittance was
      progressively lower than maximum tree height in older stands. The vertical rate
      of attenuation declined with stand age in both the overstory and understory. A
      classification of vertical light zones based on the mean and variance of
      transmittance showed a progressive widening of the bright (low variance and high
      mean) and transition (high variance and rapid vertical change) zones in older
      stands, whereas the dim zone (low variance and mean) narrowed. The zone of
      maximum canopy surface area in height profiles, estimated by inversion of
      transmittance profiles, changed from relatively high in the canopy in most young
      stands ("top-heavy") to lower in the canopy in older stands ("bottom-heavy"). In
      the understory, all stands had similar mean transmittances, but the spatial scale
      of variation increased with stand age and increasing crown size. The angular
      distribution of openness was similar in all stands, though the older stands were
      less open at all angles than the younger stands. Understory openness was
      generally unrelated to transmittance in the canopy above. Whole-canopy leaf area
      indices, estimated using three methods of inverting light measurements, showed
      little correspondence across methods. The observed patterns in light environment
      are consistent with structural changes occurring during stand development,
      particularly the diversification of crowns, the creation of openings of various
      sizes and the elaboration of the outer canopy surface. The ensemble of
      measurements has potential use in distinguishing forests of differing ages that
      have similar stature.

PMID- 11830412
TI  - Age-related variations in delta(13)C of ecosystem respiration across a coniferous
      forest chronosequence in the Pacific Northwest.
AB  - We tested the hypothesis that forest age influences the carbon isotope ratio
      (delta13C) of carbon reservoirs and CO2 at local and regional levels. Carbon
      isotope ratios of ecosystem respiration (delta13C(R)), soil respiration
      (delta13C(R-soil)), bulk needle tissue (delta13C(P)) and soil organic carbon
      (delta(13)C(SOC)) were measured in > 450-, 40- and 20-year-old temperate, mixed
      coniferous forests in southern Washington, USA. Values of delta13C(R), delta13C(R
      soil), delta13C(P) and delta13C(SOC) showed consistent enrichment with increasing
      stand age. Between the youngest and oldest forests there was an approximately 1
      per thousand enrichment in delta13C(P) (at similar canopy levels), delta13C(SOC)
      (throughout the soil column), delta13C(R-soil) (during the wet season) and
      delta13C(R) (during the dry season). Mean values of delta13C(R) were -25.9, -26.5
      and -27.0 per thousand for the 450-, 40- and 20-year-old forests, respectively.
      Both delta13C(R-soil) and the difference between delta13C(R) and delta13C(R-soil)
      were more 13C enriched in older forests than in young forest: delta13C(R) -
      delta13C(R-soil) = 2.3, 1.1 and 0.5 per thousand for the 450-, 40- and 20-year
      old forests, respectively. Values of delta(13)C(P) were proportionally more
      depleted relative to delta13C(R): delta13C(R) - delta13C(P) = 0.5, 2.2 and 2.5
      per thousand for the 450-, 40- and 20-year-old forests, respectively. Values of
      delta13C(P) were most 13C-enriched at the top of the canopy and in the oldest
      forest regardless of season (overall values were -26.9, -28.7 and -29.4 per
      thousand for the 450-, 40- and 20-year-old forests, respectively). Values of
      delta13C(SOC) from shallow soil depths were similar to delta13C(P) values of
      upper- and mid-canopy needles. All delta13C data are consistent with the
      hypothesis that a decrease in stomatal conductance associated with decreased
      hydraulic conductance leads to increased CO2 diffusional limitations in older
      coniferous trees. The strong associations between delta13C(P) in needles with
      delta13C(R) and delta13C(R-soil) at the forest level suggest that 13C
      observations scale between leaf and ecosystem levels.

PMID- 11830413
TI  - Biophysical controls of carbon flows in three successional Douglas-fir stands
      based on eddy-covariance measurements.
AB  - We measured net carbon flux (F(CO2)) and net H2O flux (F(H2O)) by the eddy
      covariance method at three Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco)
      western hemlock (Tsuga heterophylla (Raf.) Sarg.) sites located in the Wind River
      Valley of southern Washington State, USA. Stands were approximately 20, 40 and
      450 years old and measurements were made between June 15 and October 15 of 1998
      in the 40- and 450-year-old stands, and of 1999 in the 20- and 450-year-old
      stands. Our objectives were to determine if there were differences among the
      stands in: (1) patterns of daytime F(CO2) during summer and early autumn; (2)
      empirically modeled relationships between local climatic factors (e.g., light,
      vapor pressure deficit (VPD), soil water content, temperature and net radiation)
      and daytime F(CO2); and (3) water-use efficiency (WUE). We used the Landsberg
      equation, a logarithmic power function and linear regression to model
      relationships between F(CO2) and physical variables. Overall, given the same
      irradiance, F(CO2) was 1.0-3.9 mol m-2 s-1 higher (P < 0.0001 for both seasons)
      at the two young stands than at the old-growth stand. During summer and early
      autumn, F(CO2) averaged 4.2 and 6.1 mol m-2 s-1 at the 20- and 40-year-old stand,
      respectively. In contrast, the 450-year-old forest averaged 2.2 and 3.2 mol m-2 s
      1 in 1998 and 1999, respectively. Increases in VPD were associated with reduced
      F(CO2) at all three stands, with the greatest apparent constraints occurring at
      the old-growth stand. Correlations between F(CO2) and all other environmental
      variables differed among ecosystems, with soil temperature showing a negative
      correlation and net radiation showing a positive correlation. In the old-growth
      stand, WUE was significantly greater (P < 0.0001) in the drier summer of 1998
      (2.7 mg g-1) than in 1999 (1.0 mg g-1). Although we did not use replicates in our
      study, the results indicate that there are large differences in F(CO2) among
      Douglas-fir stands of different ages growing in the same general area, and that
      variations in age structure and site conditions need to be considered when
      scaling flux measurements from individual points to the landscape level.

PMID- 11830414
TI  - Use of a physiological process model with forestry yield tables to set limits on
      annual carbon balances.
AB  - We present an approach that sets limits on annual carbon fluxes for different
      aged forests by using a simple process-based model (3-PG) and information derived
      from yield tables and local weather stations. Given a measure of height-growth
      potential, model predictions are constrained to match stand dynamics described in
      yield tables. Thus constrained, the model can provide reasonable annual estimates
      of gross photosynthesis under a specified climate, even with inexact knowledge of
      soil properties. If we assume that leaf litterfall and fine-root turnover
      approach equilibrium at canopy closure, maximum net annual ecosystem exchange can
      also be predicted from modeled estimates of these two detrital components and
      estimates of foliage, branch, stem and coarse-root production. The latter four
      components of production are predicted from allometric relationships with mean
      stem diameter. The approach is demonstrated for Douglas-fir (Pseudotsuga
      menziesii (Mirb.) Franco) stands between Ages 20 and 150 years growing under
      conditions typical of those at Wind River, Washington, USA. Gross photosynthesis
      (Pg) by Douglas-fir at Ages 20, 70 and 150 years with leaf area indices (L) of
      8.1, 6.9 and 4.0 was predicted at 1630, 1580 and 1160 g C m-2 year(1,
      respectively. Maximum net ecosystem production (Pe) for the same range in age
      classes was predicted to average 275, 294 and 207 g C m-2 year-1, respectively.
      The predicted reductions in L for older stands do not occur because other species
      fill the canopy gaps created by natural mortality of Douglas-fir. As a result of
      the development of an understory, total Pg is predicted to decrease only slightly
      with the aging of the overstory. Estimates of Pe exclude respiration from coarse
      woody debris, although additions of this component are provided annually by the
      model. The process-based modeling approach, constrained by yield table estimates
      of stand properties, sets reasonable limits on annual carbon exchange and
      suggests which environmental variables deserve careful monitoring to refine
      estimates of carbon fluxes.

PMID- 11830415
TI  - Water limitations to carbon exchange in old-growth and young ponderosa pine
      stands.
AB  - We investigated the impact of seasonal soil water deficit on the processes
      driving net ecosystem exchange of carbon (NEE) in old-growth and recently
      regenerating ponderosa pine (Pinus ponderosa Doug. ex Laws.) stands in Oregon. We
      measured seasonal patterns of transpiration, canopy conductance and NEE, as well
      as soil water, soil temperature and soil respiration. The old-growth stand (O)
      included two primary age classes (50 and 250 years), had a leaf area index (LAI)
      of 2.1 and had never been logged. The recently regenerating stand (Y) consisted
      predominantly of 14-year-old ponderosa pine with an LAI of 1.0. Both stands
      experienced similar meteorological conditions with moderately cold wet winters
      and hot dry summers. By August, soil volumetric water content within the upper 30
      cm had declined to a seasonal minimum of 0.07 at both sites. Between April and
      June, both stands showed similar rates of transpiration peaking at 0.96 mm day(
      1); thereafter, trees at the Y site showed increasing drought stress with canopy
      stomatal resistance increasing 6-fold by mid-August relative to values for trees
      at the O site. Over the same period, predawn water potential (psi(pd)) of trees
      at the Y site declined from -0.54 to -1.24 MPa, whereas psi(pd) of trees at the O
      site remained greater than -0.8 MPa throughout the season. Soil respiration at
      the O site showed a strong seasonal correlation with soil temperature with no
      discernible constraints imposed by declining soil water. In contrast, soil
      respiration at the Y site peaked before seasonal maximal soil temperatures and
      declined thereafter with declining soil water. No pronounced seasonal pattern in
      daytime NEE was observed at either site between April and September. At the Y
      site this behavior was driven by concurrent soil water limitations on soil
      respiration and assimilation, whereas there was no evidence of seasonal soil
      water limitations on either process at the O site.

PMID- 11830416
TI  - Belowground carbon pools and processes in different age stands of Douglas-fir.
AB  - Forest floor material and soil organic matter may act as both a source and a sink
      in global CO2 cycles. Thus, the ecosystem processes controlling these pools are
      central to understanding the transfers of carbon (C) between the atmosphere and
      terrestrial systems. To examine these ecosystem processes, the effect of stand
      age on temporal carbon source-sink relationships was examined in 20-year-old, 40
      year-old and old-growth stands of Douglas-fir (Pseudotsuga menziesii (Mirb.)
      Franco) in the Cascade Mountains of south-central Washington State. Belowground C
      and nitrogen (N) storage and soil respiration were measured. In addition, nylon
      mesh bags containing homogenized soils from each site were buried at the
      respective sites to quantify root ingrowth and potential C sequestration and
      loss. The sites supporting the 20- and 40-year-old stands had soil C stores
      reflecting the C contributions from logging residue, coarse woody debris and
      stumps left after harvest. Because the N-fixer red alder (Alnus rubra Bong.)
      comprised 33% of the 40-year-old stand, this site had significantly greater
      concentrations and pools of N in the forest floor than sites without red alder.
      This N-rich site had consistently lower soil CO2 efflux rates during the growing
      season than the sites supporting the 20-year-old and old-growth stands. Estimated
      annual soil C efflux was 1367, 883 and 1194 g m-2 for the sites supporting the 20
      , 40- and old-growth stands, respectively. These values are higher than
      previously reported values. Root ingrowth was significantly less in the 40-year
      old stand than in the 20-year-old stand, and both young stands showed markedly
      less fine root growth than the old-growth stand. At the sites supporting the
      young stands, C and N were lost from the soil bags, whereas there was an increase
      in C and N in the soil bags at the site supporting the old-growth stand. The fine
      root growth and soil respiration data support the hypothesis that belowground C
      allocation decreases with increasing fertility. Quantification of the source-sink
      relationship of soil C at the three stands based on litterfall, relative root
      ingrowth and soil respiration measurements was compromised because of significant
      CO2 flux from decaying organic matter in the young stands.

PMID- 11830417
TI  - Canopy and hydraulic conductance in young, mature and old Douglas-fir trees.
AB  - We tested for reductions in water transport with increasing tree size, a key
      component in determining whether gas exchange and growth are hydraulically
      limited in tall trees. During the summers of 1998 and 1999, we measured water
      transport with Granier-type, constant-heat sap flow probes, vapor pressure
      deficit, and leaf and soil water potentials in overstory Pseudotsuga menziesii
      (Mirb.) Franco trees in three stands differing in size and age (15, 32 and 60 m
      in height and about 20, 40 and 450 years in age, respectively) in a P. menziesii
      dominated forest in the Pacific Northwest, USA. A total of 24 trees were equipped
      with sap flow sensors--six 60-m trees, nine 32-m trees and nine 15-m trees. Based
      on the sap flow measurements and leaf area information estimated from leaf area
      sapwood area relationships, we estimated crown-averaged stomatal conductance (GS)
      and leaf-specific hydraulic conductance (KL). We tested the hypothesis that GS
      and KL vary inversely with tree height (15 > 32 > 60 m). Analysis of variance of
      GS ranked as 15 = 60 > 32 m during the early summer and 15 > 60 > 32 m during
      late season drought. Over the growing season, mean daily GS (+/- SE) was 29.2 +/-
      4.4, 24.0 +/- 6.8 and 17.7 +/- 7.2 mmol m-2 s-1 for the 15-, 60- and 32-m trees,
      respectively. The value of K(L) differed among tree heights only during late
      season drought and ranked 15 > 32 = 60 m. A hydraulic mass balance suggests that
      greater sapwood conductivity in 60-m trees compared with 32- and 15-m trees is a
      likely cause for the departure of the above rankings from those predicted by
      height and leaf-to-sapwood area ratio.

PMID- 11830418
TI  - Trends in bole biomass accumulation, net primary production and tree mortality in
      Pseudotsuga menziesii forests of contrasting age.
AB  - Although it is generally accepted that the rate of accumulation of biomass
      declines as forests age, little is known about the relative contributions to this
      decline of changes in net primary production (NPP) and tree mortality. We used 10
      15 years of observations of permanent plots in three small watersheds in and near
      the H.J. Andrews Experimental Forest, Oregon, to examine these issues. The three
      watersheds are of similar elevation and potential productivity and support young
      (29 years at last measurement), mature (approximately 100 years) and old
      (approximately 400 years) forest dominated by Pseudotsuga menziesii (Mirb.)
      Franco and Tsuga heterophylla (Raf.) Sarg. Accumulation of tree bole biomass was
      greatest in the young stand, reaching approximately 7 Mg ha-1 year-1 in the last
      measurement interval. Bole biomass accumulation was relatively constant
      (approximately 4-5 Mg ha-1 year-1) in the mature stand, and there was no net
      accumulation of bole biomass in the old-forest stand. The NPP of boles increased
      with time in the young stand, from approximately 3 to approximately 7 Mg ha-1
      year-1, but was nearly constant in the mature and old-forest stands, at
      approximately 6 and 3-4 Mg ha-1 year-1, respectively. Mortality increased slowly
      in the young stand (from < 0.1 to 0.3 Mg ha-1 year-1), but fluctuated between 1-2
      and 2-6 Mg ha-1 year-1 in the mature and old-forest stands, respectively. Thus,
      declining biomass accumulation with stand age reflects, in approximately equal
      amounts, both decreasing NPP and increasing mortality.

PMID- 11830419
TI  - Prophylactic use of antibiotics and immunisations in patients with SLE.

PMID- 11830420
TI  - HLA-DR4 and the spondyloarthropathies.

PMID- 11830422
TI  - Erdheim-Chester disease: typical radiological bone features for a rare
      xanthogranulomatosis.

PMID- 11830421
TI  - The lung in the antiphospholipid syndrome.
AB  - Patients with antiphospholipid syndrome (APS) may develop a broad spectrum of
      pulmonary disease. Pulmonary thromboembolism and pulmonary hypertension are the
      most common complications, but microvascular pulmonary thrombosis, pulmonary
      capillaritis, and alveolar haemorrhage have also been reported. Clinicians should
      seriously consider these types of vascular injury when evaluating patients with
      APS who present with dyspnoea, fever, and infiltrates on chest radiography.

PMID- 11830423
TI  - The role of HLA genes in familial spondyloarthropathy: a comprehensive study of
      70 multiplex families.
AB  - OBJECTIVES: To investigate whether HLA alleles, other than HLA-B27, influence
      predisposition to spondyloarthropathy (SpA) in multiplex families. METHODS:
      Seventy French families with at least two affected SpA members were recruited.
      Patients, and their first degree relatives were typed for HLA-A, B, C, and DR,
      and extended HLA haplotypes were determined. The distribution of HLA-A, C, and DR
      alleles carried on HLA-B27+ haplotypes in SpA families was compared with the
      distribution of these alleles among HLA-B27+ haplotypes in the French general
      population. Contribution to SpA susceptibility of HLA-A, B, C, and DR alleles,
      other than HLA-B27, was tested by transmission disequilibrium test. The
      contribution of HLA alleles to specific presentation features of SpA was
      examined. RESULTS: Frequencies of HLA-A, C, and DR alleles carried on HLA-B27+
      haplotypes from SpA families were comparable with those seen in the French
      population, except for DR13 which was overrepresented among patients
      (pcorr<0.001). Most interestingly, the HLA-DR4 allele was transmitted in excess
      to patients with SpA, independently of linkage to HLA-B27 (pcorr=0.05), and in a
      direction opposite to that for HLA-B27+ unaffected siblings (pcorr=0.01).
      Finally, the distribution of HLA alleles was not related to the presentation
      feature of SpA. CONCLUSION: HLA predisposition to familial SpA appears not to be
      limited to HLA-B27, but some HLA-DR alleles also have a significant influence. In
      particular, HLA-DR4 contributes significantly to a genetic predisposition to SpA,
      which may have implications in our understanding of SpA pathogenesis.

PMID- 11830424
TI  - Repeated infusions of infliximab, a chimeric anti-TNFalpha monoclonal antibody,
      in patients with active spondyloarthropathy: one year follow up.
AB  - BACKGROUND: In a pilot study, the anti-tumour necrosis factor alpha monoclonal
      antibody, infliximab, induced a rapid and significant improvement in global,
      peripheral, and axial disease manifestations of patients with active
      spondyloarthropathy. OBJECTIVE: To determine whether repeated infusions of
      infliximab would effectively and safely maintain the observed effect. METHODS:
      Safety and efficacy of a maintenance regimen (5 mg/kg infliximab every 14 weeks)
      was evaluated using the measurements reported in the pilot study. Of the 21
      patients, 19 completed the one year follow up for efficacy; two patients changed
      to another dosing regimen after week 12 owing to partial lack of efficacy.
      However, they are still being followed up for safety analysis. RESULTS: After
      each re-treatment a sustained significant decrease of all disease manifestations
      was observed. Before re-treatment, symptoms recurred in 3/19 (16%) at week 20, in
      13/19 (68%) at week 34, and in 15/19 (79%) at week 48. No withdrawals due to
      adverse events occurred. Twelve minor infectious episodes were observed. Twelve
      patients (57%) developed antinuclear antibodies; in four of them (19%) anti-dsDNA
      antibodies were detected. However, no lupus-like symptoms occurred. CONCLUSION:
      In this open study of infliximab in patients with active spondyloarthropathy, the
      significant improvement of all disease manifestations was maintained over a one
      year follow up period without major adverse events. Although recurrence of
      symptoms was noted in a rising number of patients before each re-treatment, no
      loss of efficacy was observed after re-treatment.

PMID- 11830425
TI  - Differential association of polymorphisms in the TNFalpha region with psoriatic
      arthritis but not psoriasis.
AB  - OBJECTIVE: To investigate the potential association of tumour necrosis factor
      alpha (TNFalpha) microsatellite and promoter alleles with psoriatic arthritis
      (PsA). METHODS: DNA from 89 white patients with PsA, 65 patients with psoriasis,
      and 99 healthy white controls was investigated for two TNFalpha promoter (-238
      and -308) and three microsatellite polymorphisms (TNFa, c, and d). Patients had
      previously been studied by serology for HLA class I antigens and by sequence
      specific polymerase chain reaction for DRB1* alleles. In addition, TNFalpha
      production of Ficoll separated peripheral blood mononuclear cells (PBMC) into
      culture supernatants after stimulation with lipopolysaccharide, alphaCD3
      antibodies, phytohaemagglutinin, and streptococcal superantigen C was determined.
      RESULTS: A significant, HLA class I independent increase of the TNFa6c1d3
      haplotype was found in the group with PsA but not among patients with psoriasis
      (32% v. 8%, pc<0.008; relative risk (RR)=5.3). In addition, patients with PsA
      showed a marked decrease of the TNF308A promoter allele (6% v. 18%; pc<0.008;
      RR=3.5) compared with healthy controls, which was independent of the increased
      frequency of the -238A polymorphism in this group. PBMC from patients with PsA
      secreted significantly less TNFalpha than cells from patients without arthritis.
      In particular, the TNFa6 microsatellite was associated with decreased TNFalpha
      production. CONCLUSION: These data indicate that allelic variations at the
      TNFalpha locus influence susceptibility to PsA. Decreased production of TNFalpha
      is at least in part genetically determined and might be related to the
      development of arthritis. However, the association of the TNF308G allele with the
      disease also points to other disease related haplotypes with still unknown
      susceptibility genes.

PMID- 11830426
TI  - Psoriatic arthritis: performance of rheumatologists in daily practice.
AB  - OBJECTIVES: To assess, using standardised patients (SPs), how rheumatologists
      diagnose psoriatic arthritis, whether the diagnostic efficiency is influenced by
      specific characteristics of the rheumatologists, and to study the relationship
      with costs. METHODS: Twenty three rheumatologists were each visited by one of two
      SPs (one male, one female) presenting as a patient with psoriatic arthritis. SPs
      remained incognito for all meetings for the duration of the study. Immediately
      after the encounter, SPs completed case-specific checklists on the medical
      content of the encounter. Information on ordered laboratory and imaging tests was
      obtained from each hospital. RESULTS: Fourteen rheumatologists diagnosed
      psoriatic arthritis correctly. They inspected the skin for psoriatic lesions more
      often than those rheumatologists who established other diagnoses. Rheumatologists
      diagnosing psoriatic arthritis spent more on additional laboratory and imaging
      investigations. These were carried out after the diagnosis to confirm it and to
      record the extent and severity of the disease. No differences in type of
      practice, number of outpatients seen each week, working experience, or sex were
      found between rheumatologists who made the correct diagnosis and those who made
      other diagnoses. The correct diagnosis was more often missed by rheumatologists
      who saw the male SP, who presented with clear distal interphalangeal DIP joint
      arthritis only, causing confusion with osteoarthritis of the DIP joints.
      CONCLUSION: There is a considerable amount of variation in the delivery of care
      among rheumatologists who see an SP with psoriatic arthritis. Rheumatologists
      focusing too much on the most prominent features (DIP joint arthritis) sometimes
      seem to forget "the hidden (skin) symptoms".

PMID- 11830427
TI  - The ICIDH-2 as a framework for the assessment of functioning and disability in
      rheumatoid arthritis.
AB  - OBJECTIVE: To investigate by a cross sectional study in patients with rheumatoid
      arthritis (RA) the relationship between measures of impairment, activity
      limitation, and participation of the model of functioning and disability (ICIDH
      2). METHODS: Inclusion data of patients with RA (n=803) from the Swiss Clinical
      Quality Management Group were used. Impairments were measured by the Short Form
      36 (SF-36) bodily pain scale, rheumatoid arthritis disease activity index
      (RADAI), disease activity score (DAS28), and radiographic scoring (x ray).
      Activity limitation was measured with the Health Assessment Questionnaire (HAQ)
      and the SF-36 physical functioning scale. Participation was measured with the SF
      36 role and social functioning scales. Spearman (partial) correlations were used
      for analysis. RESULTS: Impairment and activity limitation dimensions of the ICIDH
      2 model are related; correlations with the HAQ were: SF-36 bodily pain (r(s)=
      0.61), RADAI (r(s)=0.58), DAS28 (r(s)=0.49), and x ray (r(s)=0.35). Similar
      correlations were found for SF-36 physical functioning. Activity limitation and
      participation restriction dimensions are also related: the HAQ correlates well
      with SF-36 role-physical (r(s)=-0.53) and SF-36 social functioning (r(s)=-0.43);
      SF-36 physical functioning correlates similarly. For impairment and participation
      restriction dimensions only SF-36 bodily pain is substantially correlated
      (r(s)=0.47 and 0.48) with SF-36 role-physical, after correcting for the influence
      of the activity limitation dimension (HAQ and SF-36 physical functioning).
      CONCLUSIONS: In this cross sectional study of patients with RA, impairments are
      associated with activity limitations, and activity limitations are associated
      with participation restrictions. Pain is the only impairment directly associated
      with participation restrictions. Based on the results of this study, it is
      strongly recommended that the ICIDH-2 framework is used in clinical trials and
      observational studies including the assessment of disease consequences in RA.

PMID- 11830428
TI  - Spectral analysis of heart rate and blood pressure variability in primary
      Sjogren's syndrome.
AB  - BACKGROUND: Autonomic dysfunction has been described in primary Sjogren's
      syndrome (SS). OBJECTIVE: To investigate the circulatory autonomic regulation in
      patients with primary SS by power spectral analysis of heart rate and blood
      pressure variability. METHODS: Forty three (42 female) patients with primary SS,
      mean age 52 years (range 23-80), with a mean disease duration of eight years
      (range 1-30) and 30 (15 female) healthy controls, mean age 43 years (range 21-68)
      were studied. In each patient blood pressure, heart rate, and respiration were
      measured continuously during supine rest and orthostatic challenge (60 degrees
      head-up tilt). Power spectral analysis was performed to determine possible
      differences in short term sympathetic and parasympathetic autonomic regulation
      between patients and controls. Furthermore, spectral parameters were studied in
      relation to illness severity and disease duration of the patients with primary
      SS. RESULTS: After controlling for differences in age, heart rate variability of
      the mid-frequency band and the variation coefficient of systolic blood pressure
      were significantly lower in patients with primary SS than in controls during
      supine rest. During 60 degrees tilt patients with primary SS showed a
      significantly higher mean heart rate, mean systolic blood pressure, and variation
      coefficient of diastolic blood pressure, and a significantly lower baroreflex
      index than controls. After controlling for age, no differences were found either
      in heart rate variability, blood pressure results, and baroreflex sensitivity
      during supine rest and tilt between the subgroups divided according to disease
      duration, Schirmer test results, or between the subgroups with different fatigue
      scores. No differences were found in spectral data between the groups with and
      without positive antinuclear antibody serology. CONCLUSION: For the group no
      differences in sympathetic and parasympathetic cardiac control were seen between
      patients with primary SS and controls, as assessed by spectral techniques,
      although some cardiovascular differences were found, particularly during
      orthostatic challenge.

PMID- 11830429
TI  - Non-invasive measurement of biomechanical skin properties in systemic sclerosis.
AB  - OBJECTIVE: To evaluate biomechanical properties of skin in patients with systemic
      sclerosis (SSc) using the BTC-2000 suction device. METHODS: Twenty five patients
      with limited cutaneous SSc (lcSSc), 20 patients with diffuse disease (dcSSc), and
      25 age matched healthy controls were evaluated. Viscoelastic deformation (VED,
      mm), elastic deformation (ED, mm), ultimate deformation (UD, mm), and pressure
      deformation ratio (PDR, mm Hg/mm) were measured on the dorsal surface of the
      forearm, shoulder, and above the trapezius muscle on the back. RESULTS: Indices
      of skin extensibility (VED, ED, UD) were reduced and resistance to stress (PDR)
      increased in patients with dcSSc compared with healthy controls, or patients with
      lcSSc, at all three sites (p<0.001). At all sites, and overall, UD, ED, and VED
      were lower and PDR was higher at skin score above grade 2, compared with
      clinically normal skin. For both lcSSc and dcSSc biomechanical differences from
      controls were found even at sites of clinically normal skin. CONCLUSION: BTC-2000
      is a sensitive tool for clinical evaluation of skin involvement in SSc and may be
      a valuable adjunct to skin sclerosis score in disease monitoring.

PMID- 11830430
TI  - Circulating soluble E-selectin in early rheumatoid arthritis: a prospective five
      year study.
AB  - BACKGROUND: Soluble E-selectin (sE-selectin) is a marker of activation of
      vascular endothelium. OBJECTIVE: To examine serum levels of sE-selectin in a
      cohort of 85 patients with early rheumatoid arthritis (RA) followed up for five
      years. METHODS: sE-selectin levels were assessed annually using an enzyme linked
      immunosorbent assay (ELISA) and related to simultaneously obtained clinical and
      laboratory measures. Joint inflammation was evaluated by active joint count,
      functional status by Health Assessment Questionnaire (HAQ), and radiographic
      findings in hands and feet by the Larsen method. Laboratory tests included serum
      C reactive protein (CRP) level, erythrocyte sedimentation rate, blood haemoglobin
      level, white blood cell count (WBC), and platelet count. Area under the curve
      (AUC) was calculated for each variable, and Jonckheere's test for ordered
      alternatives was applied to assess significance of association between sE
      selectin AUC tertiles and other variables. Baseline sE-selectin tertiles were
      related to change in Larsen score and HAQ score at five years. Odds ratios (OR)
      with 95% confidence interval (CI) were calculated using univariate and
      multivariate logistic regression. RESULTS: sE-selectin levels were associated
      with CRP level (p=0.012), WBC (p=0.037), active joint count (p=0.019),
      progression of joint destruction (p=0.038), and HAQ score at five years
      (p=0.021), but not with extra-articular symptoms or comorbidity. Baseline sE
      selectin levels in the third tertile predicted the HAQ score at five years (OR
      4.18, 95% CI 1.15 to 15.22). sE-selectin levels of patients did not differ
      significantly from those of healthy control subjects. CONCLUSION: The degree of
      activation of vascular endothelium is associated with activity and outcome of
      early RA.

PMID- 11830431
TI  - Weather and the pain in fibromyalgia: are they related?
AB  - OBJECTIVES: To examine the association between fibromyalgic pain and weather to
      determine the nature of their interrelationship. METHODS: The daily pain ratings
      of 55 female patients previously diagnosed with fibromyalgia were recorded on
      visual analogue scales (VAS) over 28 days. These ratings were then related to the
      official weather parameters and a composite weather variable using time series
      methodology. Effect sizes r were calculated from the t values and df. RESULTS: A
      composite weather variable did not significantly predict changes in pain, either
      the same day (t=-1.15, df=1483, p=0.25) or on the next day (t=-1.55, df=1483,
      p=0.12)-that is, the weather was not a factor for changes in the subjective pain
      of FM. Patients' pain did not predict weather change in this sample, and neither
      same day (t=-0. 69, df=1483, p<0.49) nor previous day pain (t=-1.31, df=1483,
      p<0.19) predicted weather changes. A post hoc exploratory analysis showed that
      those with <10 years of fibromyalgia experienced significantly greater weather
      sensitivity to pain (t=- 2.73, df=389, p<0.006) than those with longer illness.
      CONCLUSION: A statistically significant relationship between fibromyalgic pain
      and the weather was not found in this sample, although it is possible that a
      group of patients with less chronic fibromyalgia might be weather sensitive.

PMID- 11830432
TI  - Efficacy of isoniazid prophylaxis in patients with systemic lupus erythematosus
      receiving long term steroid treatment.
AB  - OBJECTIVE: To study the efficacy of isoniazid prophylaxis (INHP) in patients with
      systemic lupus erythematosus (SLE) receiving long term glucocorticosteroid
      treatment. PATIENTS AND METHODS: Treatment with INHP (5 mg/kg/day, max 300
      mg/day) together with pyridoxine 10 mg/day for one year was started in all
      patients with SLE seen between January 1994 and December 1999 and followed up
      thereafter. Clinical examination and chest radiography were carried out in all
      patients before the start of INHP treatment. A liver profile was obtained only if
      liver toxicity was suspected owing to nausea, loss of appetite, and icterus. Only
      the data of those patients who completed the INHP treatment or who were withdrawn
      owing to toxicity have been analysed. This was compared with the results of an
      earlier study of the incidence of tuberculosis (TB) in patients with SLE not
      receiving INHP. RESULTS: Ninety seven patients were included, of whom 95
      completed one year's treatment with INHP. Treatment was discontinued in two owing
      to toxicity: hepatitis in one and peripheral neuropathy in one, at eight and 10
      months, respectively. One patient developed TB within one month of starting INHP.
      Seventy patients were followed up further for at least one year (mean 26.4
      months, range 12-60 months) after completion of the INHP treatment. During this
      period one patient developed TB after one month. No deaths due to TB or hepatitis
      occurred. In comparison with earlier series the incidence of TB decreased from
      11% to 2%, a reduction of 82%. The cost of treatment for each case of TB
      prevented in the first year was 5800 rupees. CONCLUSION: INHP is safe and
      effective in SLE.

PMID- 11830433
TI  - Soluble tumour necrosis factor receptor treatment does not affect raised
      transforming growth factor beta levels in rheumatoid arthritis.
AB  - OBJECTIVE: To further elucidate the immunomodulating effects of anti-tumour
      necrosis factor alpha treatment in rheumatoid arthritis (RA) by studying changes
      in plasma levels of transforming growth factor beta (TGFbeta) in patients with RA
      undergoing etanercept treatment. METHODS: Plasma levels of TGFbeta1 and TGFbeta2
      were determined in 26 patients with RA during six months of etanercept treatment
      and compared with disease activity and laboratory parameters, including matrix
      metalloproteinase-3 (MMP-3) and interleukin 6 (IL6). RESULTS: Before treatment
      all patients had raised TGFbeta1, IL6, and MMP-3 levels. In the course of
      treatment IL6 and MMP-3 levels decreased significantly, accompanied by a drop in
      serological markers (C reactive protein and erythrocyte sedimentation rate) and
      clinical disease activity (visual analogue scale and Thompson joint score). By
      contrast, high levels of latent TGFbeta1 were present in all specimens over the
      entire six months. TGFbeta2 levels did not change during treatment. CONCLUSION:
      Etanercept treatment induces subtle changes in the cytokine network. Although the
      proinflammatory cytokine IL6 is down regulated, the persistence of high TGFbeta
      plasma levels indicates the existence of as yet unknown mechanisms for TGFbeta
      overexpression in RA. This may predispose to severe infections and can cause an
      altered tumour defence.

PMID- 11830435
TI  - Correlation between plasma concentrations of calcitonin gene related peptide and
      pulmonary pressure in patients with systemic sclerosis.
AB  - OBJECTIVE: To examine plasma levels of calcitonin gene related peptide (p-CGRP)
      in patients with systemic sclerosis (SSc) and pulmonary hypertension (PH).
      MATERIAL AND METHODS: Twenty nine patients with SSc, 10 with diffuse form, 18
      with limited form and one with overlapping systemic lupus erythematosus were
      examined. Twelve patients displayed normal systolic pulmonary artery pressure
      (PAPsyst) < or =30 mm Hg and 17 increased PAPsyst >30 mm Hg. Eight patients had
      isolated PH without interstitial lung disease (ILD) and nine had PH and ILD
      (secondary PH). PAPsyst was measured non-invasively by Doppler cardiography. CGRP
      was determined by radioimmunoassay. RESULTS: Patients with PH had higher p-CGRP
      than patients with normal pressure. A positive relation was found between p-CGRP
      and PAPsyst and between p-CGRP and erythrocyte sedimentation rate (ESR),
      particularly in patients with isolated PH. CONCLUSION: In patients with SSc p
      CGRP correlates with pulmonary pressure and with ESR. Whether CGRP reflects
      disease activity or is released secondary to pulmonary vasoconstriction needs to
      be investigated further.

PMID- 11830434
TI  - Deficiency of complement-dependent prevention of immune precipitation in systemic
      sclerosis.
AB  - BACKGROUND: Previous studies have indicated that complement may be activated or
      inherently abnormal in systemic sclerosis (SSc), and it has been suggested that
      immune complex deposition plays a part in the microvascular damage of this
      disease. OBJECTIVE: To study several aspects of the complement system in 24
      patients with SSc. METHODS: Complement dependent prevention of immune
      precipitation (PIP) was measured by a sensitive enzyme immunoassay, levels of
      C1q, C4, and C3 by rocket immunoelectrophoresis, C4 allotypes by high voltage
      agarose electrophoresis, and C4A, C4B, and C3d by an enzyme linked immunosorbent
      assay (ELISA). RESULTS: PIP was markedly decreased in the patients with SSc
      (p<0.001). Abnormal complement activation was detected in nine patients as raised
      levels of the complement split product C3d. However, a relation between low PIP
      and complement activation was not seen. PIP was significantly lower in patients
      who carried the C4A*Q0 allotype (p=0.03), and a strong correlation was found
      between PIP and C4A concentration (p<0.00001). The PIP defect may, at least in
      some patients, be associated with the initial phase of the disease. CONCLUSIONS:
      The results show a previously unrecognised functional defect of complement in
      SSc; the defect correlates with low levels of classical pathway components and,
      in particular, C4A.

PMID- 11830436
TI  - Reactive arthritis following an outbreak of Salmonella typhimurium phage type 193
      infection.
AB  - OBJECTIVES: To determine the occurrence and the clinical picture of reactive
      arthritis (ReA) following an outbreak of Salmonella typhimurium. METHODS: An
      outbreak of S typhimurium phage type DT 193 occurred in several municipalities in
      Finland in 1999. A questionnaire which had a specific emphasis on musculoskeletal
      symptoms was mailed to all 78 subjects with a positive stool culture. Based on
      the answers, all subjects with recent joint complaints were clinically examined
      or interviewed by telephone. RESULTS: Sixty three of 78 subjects (81%) returned
      the questionnaire. Of these 63 subjects, five (8%) fulfilled the criteria for
      ReA. All the five subjects with ReA were adults with oligo- or polyarthritis. The
      antigen HLA-B27 was positive in two of the four subjects tested. In two of five
      subjects with ReA, the duration of acute arthritis was over six months. Subjects
      who had received antimicrobial drugs developed acute musculoskeletal symptoms
      significantly (p=0.013) less often than those without such treatment. None of the
      subjects with ReA had received antimicrobial drugs before the onset of joint
      symptoms. CONCLUSIONS: The occurrence of ReA following an outbreak of S
      typhimurium was at the same level as in outbreaks due to other salmonella
      serotypes reported previously by us, indicating that the frequency of ReA after
      various outbreaks is approximately 10%. Early use of antimicrobial drugs may
      prevent the development of musculoskeletal symptoms.

PMID- 11830437
TI  - No changes in the distribution of organisms responsible for septic arthritis over
      a 20 year period.
AB  - OBJECTIVE: To assess changes in the distribution and resistance of the pathogens
      responsible for septic arthritis over a 20 year period in patients admitted to
      the same hospital unit. PATIENTS AND METHODS: Retrospective study of the hospital
      records of patients admitted between 1979 and 1998 for septic arthritis with
      positive microbiological diagnosis after blood or joint cultures, or both.
      RESULTS: 303 cases of septic arthritis were studied, 141 in the period 1979-88
      and 162 in the period 1989-98. The incidence between the first and second period
      did not vary significantly for the staphylococci (67% v. 63%), streptococci (16%
      v. 20%), and Gram negative bacilli (7% v. 10%). Tuberculous infections decreased
      from 9% to 4% (p<0.04). No gonococci were isolated in the second 10 year period.
      Among the staphylococcal species, there was an increase in the number of
      coagulase negative staphylococci (10 cases v. 21, p<0.05) between the two
      periods. There was no significant difference in the frequency of occurrence of
      methicillin resistant pathogens (12.6% v. 16.6%). The number of streptococcal B
      infections increased (2 v. 10 cases), and beta-lactamine resistant pneumococci
      emerged. In the second 10 year period, patients were older and were more likely
      to have co-existing disease, particularly tumoral growth, and less commonly were
      receiving dialysis. Localisation of joint infection was comparable except for an
      increase in prosthetic knee infections. CONCLUSION: The distribution and
      sensitivity of pathogens causing septic arthritis changed little over a 20 year
      period.

PMID- 11830438
TI  - Factors related to radiological damage in 61 Spaniards with early rheumatoid
      arthritis.
AB  - OBJECTIVE: To determine whether the presence of radiographic erosions at disease
      onset in patients with early rheumatoid arthritis (RA) is associated with
      clinical, serological, or genetic factors of poor outcome and whether patients
      with erosions only in the feet have a different pattern of presentation. METHODS:
      Sixty one patients with early RA (<6 months of evolution) were studied. Clinical
      evaluation and serological, radiological, and genetic studies were performed at
      disease onset and after one year. RESULTS: Forty one (67%) patients showed
      erosions in their hands or in their feet, or in both. Subjects with erosive RA
      had a higher number of swollen joints (SJN; 9 (SD 6) v. 6 (3), p=0.008), and
      rheumatoid factor (RF) positivity was more common (80% v. 50%, p<0.02) than those
      without erosions. Seven (17%) of the 41 patients in the group with erosions had
      erosions only in their feet. This group had a longer duration of morning
      stiffness (120 (60) v. 72 (52) min, p<0.005), better patient's global assessment
      of general health (34 (22) v. 57 (25), p< 0.05), and lower erythrocyte
      sedimentation rate (32 (22) v. 60 (30) mm/1st h, p <0.05) than the rest of the
      subjects with erosions, and none of them was in remission after one year.
      Remission after one year was related to a lack of cortical damage at onset and RF
      negativity. CONCLUSIONS: Radiological damage at disease onset is associated with
      a worse clinical presentation and RF positivity, which are markers of poor
      outcome. There is a subgroup of patients, with erosions only in their feet, whose
      clinical presentation is less aggressive. To identify these cases of early
      erosive RA, radiographs of the feet should be obtained routinely.

PMID- 11830439
TI  - A brief history of spa therapy.
AB  - Bathing in thermal water has an impressive history and continuing popularity. In
      this paper a brief overview of the use of water in medicine over the centuries is
      given.

PMID- 11830440
TI  - Sonography as a replacement for sialography for the diagnosis of salivary glands
      affected by Sjogren's syndrome.

PMID- 11830441
TI  - Home sequential high dose intravenous immunoglobulins in systemic autoimmune
      disease.

PMID- 11830442
TI  - Nail lesions in psoriatic arthritis: recovery with sulfasalazine treatment.

PMID- 11830443
TI  - Elastofibroma dorsi.

PMID- 11830444
TI  - Olecranon bursitis due to Candida parapsilosis in an immunocompetent adult.

PMID- 11830445
TI  - Henoch-Schonlein purpura: a possible complication of hepatitis C related liver
      cirrhosis.

PMID- 11830446
TI  - Prevalence of allergic respiratory diseases in patients with RA.

PMID- 11830447
TI  - Severe aortic regurgitation in RF positive polyarticular JIA.

PMID- 11830448
TI  - Remission of Behcet's syndrome with TNFalpha blocking treatment.

PMID- 11830449
TI  - Polymyalgia rheumatica and pericardial tamponade.

PMID- 11830450
TI  - Fatigue and immune activity in Sjogren's syndrome.

PMID- 11830454
TI  - Arginine supplementation of sickle transgenic mice reduces red cell density and
      Gardos channel activity.
AB  - Nitric oxide (NO), essential for maintaining vascular tone, is produced from
      arginine by nitric oxide synthase. Plasma arginine levels are low in sickle cell
      anemia, and it is reported here that low plasma arginine is also found in our
      sickle transgenic mouse model that expresses human alpha, human beta(S), and
      human beta(S-Antilles) and is homozygous for the mouse beta(major) deletion (S+S
      Antilles). S+S-Antilles mice were supplemented with a 4-fold increase in arginine
      that was maintained for several months. Mean corpuscular hemoglobin concentration
      (MCHC) decreased and the percent high-density red cells was reduced. Deoxy K(+)
      efflux is characteristic of red cells in sickle cell disease and contributes to
      the disease process by increasing the MCHC and rendering the cells more
      susceptible to polymer formation. This flux versus the room air flux was reduced
      in S+S-Antilles red cells from an average value of 1.6 +/- 0.3 mmol per liter of
      red cells x minute (FU) in nonsupplemented mice to 0.9 +/- 0.3 FU (n = 4, P <
      .02, paired t test) in supplemented mice. In room air, V(max) of the Ca(++)
      activated K(+) channel (Gardos) was reduced from 4.1 +/- 0.6 FU (off diet) to 2.6
      +/- 0.4 FU (n = 7 and 8, P < .04, t test) in arginine-supplemented mice versus
      clotrimazole. In conclusion, the major mechanism by which arginine
      supplementation reduces red cell density (MCHC) in S+S-Antilles mice is by
      inhibiting the Ca(++)-activated K(+) channel.

PMID- 11830455
TI  - Up-regulation of the chemokine receptor CCR7 in classical but not in lymphocyte
      predominant Hodgkin disease correlates with distinct dissemination of neoplastic
      cells in lymphoid organs.
AB  - Chemokines and chemokine receptors are key mediators for regulating cell traffic
      and positioning in both homeostatic and inflammatory conditions. It is also
      presumed that chemokines and their receptors are likely to play a critical role
      in the localization of malignant hematopoietic cells in their target organs. This
      study analyzed chemokine and chemokine receptor expression in several Hodgkin
      disease (HD)-derived cell lines and in HD tumors. All HD-derived cell lines
      expressed functional CCR7 and CXCR4 receptors. CCR7 up-regulation was mediated by
      constitutive NF-kappaB activity. Lymphoid tissues in HD revealed differential
      expression levels of CCR7, CXCR4, and CXCR5, depending on the distinct subtypes
      of HD. HD of the classical subtypes, predominantly located in the interfollicular
      zone, showed strong CCR7 and CXCR4 expression and moderate CXCR5 expression. In
      contrast, the nodular lymphocyte-predominant HD (NLP) subtype, regularly
      associated with follicular structures, exhibited no CCR7 reactivity but abundant
      CXCR4 staining. Their respective chemokine ligands showed marked expression by
      reactive cells within the tumors of classical HD and outside of the tumor nodules
      in NLPHD. Functionally, such differential chemokine receptor expression might
      contribute to specific localization and confinement of neoplastic cells within
      the target organs in the distinct HD entities.

PMID- 11830456
TI  - Stromal cell-derived factor 1 regulates primitive hematopoiesis by suppressing
      apoptosis and by promoting G(0)/G(1) transition in CD34(+) cells: evidence for an
      autocrine/paracrine mechanism.
AB  - The stromal cell-derived factor 1 (SDF-1) chemokine has various effects on
      hematopoietic cell functions. Its role in migration and homing of hematopoietic
      progenitors is currently well established. Previously it was shown that SDF-1
      stimulates myeloid progenitor proliferation in synergy with cytokines. Results of
      this study indicate that SDF-1 alone promotes survival of purified CD34(+) cells
      from human unmobilized peripheral blood (PB) by counteracting apoptosis as
      demonstrated by its capacity to reduce DNA fragmentation, annexin-V(+) cell
      number, and APO2.7 detection and to modulate bcl-2 homolog protein expression.
      The study demonstrates that SDF-1, produced by sorted CD34(+)CD38(+) cells and
      over-released in response to cell damage, exerts an antiapoptotic effect on
      CD34(+) cells through an autocrine/paracrine regulatory loop. SDF-1 participates
      in the autonomous survival of circulating CD34(+) cells and its effect required
      activation of the phosphotidyl inositol 3 kinase (PI3-K)/Akt axis. Cell sorting
      based on Hoechst/pyroninY fluorescences shows that SDF-1 production is restricted
      to cycling CD34(+) cells. SDF-1 triggers G(0) quiescent cells in G(1) phase and,
      in synergy with thrombopoietin or Steel factor, makes CD34(+) cells progress
      through S+G(2)/M phases of cell cycle. By assessing sorted CD34(+)CD38(-) and
      CD34(+)CD38(+) in semisolid culture, the study demonstrates that SDF-1 promotes
      survival of clonogenic progenitors. In conclusion, the results are the first to
      indicate a role for endogenous SDF-1 in primitive hematopoiesis regulation as a
      survival and cell cycle priming factor for circulating CD34(+) cells. The
      proposal is made that SDF-1 may contribute to hematopoiesis homeostasis by
      participating in the autonomous survival and cycling of progenitors under
      physiologic conditions and by protecting them from cell aggression in stress
      situations.

PMID- 11830457
TI  - Improved disease-free-survival after transplantation of peripheral blood stem
      cells as compared with bone marrow from HLA-identical unrelated donors in
      patients with first chronic phase chronic myeloid leukemia.
AB  - Outcomes after peripheral blood stem cell transplantation (PBSCT) for chronic
      phase chronic myeloid leukemia (n = 37) were compared with outcomes after bone
      marrow transplantation (BMT) (n = 54) in the HLA-compatible unrelated donor
      setting. Median follow-up was 17 months after PBSCT and 29 months after BMT. Both
      neutrophil and platelet recovery were faster after PBSCT (P <.05). PBSCT was
      associated with improved immune reconstitution, with higher peripheral blood
      naive (CD4(+)CD45RA(+)) and memory (CD4(+) CD45RO(+)) helper T cells at 3 months
      and 12 months after transplantation (P <.03). The cumulative incidence of acute
      (grades II-IV) and chronic graft-versus-host disease (GVHD) were similar, but BMT
      was associated with a higher cumulative incidence of severe, acute (grade III-IV)
      GVHD at 24% as compared with 8% with PBSCT (P <.05). Molecular relapse, defined
      by 2 consecutive positive polymerase chain reaction assays for bcr-abl within a 4
      week interval, occurred in 12 of 45 evaluable patients (27%) after BMT and in 4
      of 37 (11%) after PBSCT (not significant). Cytogenetic relapse occurred in 5 of
      54 patients after BMT (9%) and in 1 of the 37 (3%) patients after PBSCT (not
      significant). Seventeen of the 54 patients died after BMT (31%), as compared with
      2 of 37 patients after PBSCT (5%). Deaths in the BMT group were associated mainly
      with infections and severe, acute GVHD. The estimated probability of transplant
      related mortality (TRM) and disease-free survival at 1000 days after receiving
      the transplant were 30% and 64% in the BMT group and 5% and 91% in the PBSCT
      group (P <.03). Overall survival 1000 days after receiving the transplant was 66%
      after BMT and 94% after PBSCT (P <.02). In the multivariate analysis, only acute
      GVHD significantly influenced TRM (P <.01).

PMID- 11830458
TI  - Germinal center phenotype and bcl-2 expression combined with the International
      Prognostic Index improves patient risk stratification in diffuse large B-cell
      lymphoma.
AB  - The International Prognostic Index (IPI) identifies poor- and good-risk patients
      with diffuse large B cell lymphoma (DLBCL); however, the majority of patients
      have an intermediate IPI, with an uncertain prognosis. To determine whether
      cellular factors can be combined with the IPI to more accurately predict outcome,
      we have analyzed 177 presentation nodal DLBCLs for the expression of bcl-2 and a
      germinal center (GC) phenotype (defined by expression of bcl-6 and CD10). P53
      gene band shifts were detected using single-stranded conformational polymorphism
      polymerase chain reaction analysis of exons 5-9 and were correlated with protein
      expression. In a Cox regression analysis, IPI (R = 0.22, P <.0001) and bcl-2 (R =
      0.14, P =.0001) were independent poor prognostic factors and a GC phenotype
      predicted a favorable outcome (R = -0.025, P =.02). Neither p53 expression nor
      band shifts had a significant effect on survival. Using the IPI alone, 8% of
      patients were identified as high risk. Expression of bcl-2 in the intermediate
      IPI group identified a further 28% of patients with an overall survival
      comparable to the high IPI group. In the intermediate IPI, bcl-2(-) group, the
      presence of a GC phenotype improved overall survival to levels approaching the
      IPI low group. Following this analysis only 15% of patients failed to be assigned
      to a favorable- or poor-risk group. Sequential addition of bcl-2 expression and
      GC phenotype into the IPI significantly improves risk stratification in DLBCL.
      For the 36% of high-risk patients with a 2-year overall survival of 19%,
      alternative treatment strategies should be considered in future trials.

PMID- 11830459
TI  - The diagnosis and management of polycythemia vera in the era since the
      Polycythemia Vera Study Group: a survey of American Society of Hematology
      members' practice patterns.
AB  - The Polycythemia Vera Study Group (PVSG) was organized in 1967 to identify the
      optimal approach to the diagnosis and treatment of polycythemia vera (PV).
      Nevertheless, a systematic assessment of US physicians' approach to PV has not
      been performed. To determine practice patterns in the management of PV, a random
      sample of the US American Society of Hematology (ASH) membership was surveyed.
      Thirty-three percent of 3000 surveys were returned. Significant variations in
      diagnostic and therapeutic approach were evident by region, practice type,
      specialty, and clinical experience. Red cell volume determinations (78% of
      respondents), serum erythropoietin levels (76%), and arterial blood gases (75%)
      were the most frequent tests used in the diagnosis of PV. Sixty-nine percent of
      physicians use phlebotomy as their first choice for erythrocytosis. Phlebotomy
      plus hydroxyurea (27.8%) and hydroxyurea alone (10%) were used less often.
      Despite PVSG recommendations, almost 16% of physicians used a target hematocrit
      of 0.55 (50%) or 0.55 (55%) for phlebotomy therapy. Eighty-two percent of
      physicians treated thrombocytosis only when platelet counts exceeded 1000 x
      10(9)/L (1 000 000/microL) or in the event of symptoms. Hydroxyurea (62.8%) and
      anagrelide (35.4%) were the primary agents used to treat thrombocytosis. Thus,
      this national survey of US hematologists and oncologists has identified
      substantial variation in the approach to the diagnosis and treatment of PV. A
      significant minority of physicians undertreat erythrocytosis, and little
      consensus exists regarding the treatment of thrombocytosis.

PMID- 11830460
TI  - Oligodeoxynucleotide-mediated inhibition of c-myb gene expression in autografted
      bone marrow: a pilot study.
AB  - Antisense oligodeoxynucleotide (ODN) drugs might be more effective if their
      delivery was optimized and they were targeted to short-lived proteins encoded by
      messenger RNA (mRNA) species with equally short half-lives. To test this
      hypothesis, an ODN targeted to the c-myb proto-oncogene was developed and used to
      purge marrow autografts administered to allograft-ineligible chronic myelogenous
      leukemia patients. CD34(+) marrow cells were purged with ODN for either 24 (n =
      19) or 72 (n = 5) hours. After purging, Myb mRNA levels declined substantially in
      approximately 50% of patients. Analysis of bcr/abl expression in long-term
      culture-initiating cells suggested that purging had been accomplished at a
      primitive cell level in more than 50% of patients and was ODN dependent. Day-100
      cytogenetics were evaluated in surviving patients who engrafted without infusion
      of unmanipulated "backup" marrow (n = 14). Whereas all patients were
      approximately 100% Philadelphia chromosome-positive (Ph(+)) before
      transplantation, 2 patients had complete cytogenetic remissions; 3 patients had
      fewer than 33% Ph(+) metaphases; and 8 remained 100% Ph(+). One patient's marrow
      yielded no metaphases, but fluorescent in situ hybridization evaluation
      approximately 18 months after transplantation revealed approximately 45%
      bcr/abl(+) cells, suggesting that 6 of 14 patients had originally obtained a
      major cytogenetic response. Conclusions regarding clinical efficacy of ODN marrow
      purging cannot be drawn from this small pilot study. Nevertheless, these results
      lead to the speculation that enhanced delivery of ODN, targeted to critical
      proteins of short half-life, might lead to the development of more effective
      nucleic acid drugs and the enhanced clinical utility of these compounds in the
      future.

PMID- 11830461
TI  - Randomized multicenter trial of foscarnet versus ganciclovir for preemptive
      therapy of cytomegalovirus infection after allogeneic stem cell transplantation.
AB  - The present study compared foscarnet with ganciclovir for preemptive therapy of
      cytomegalovirus (CMV) infection after allogeneic blood or marrow stem cell
      transplantation (SCT). Patients with CMV infection, as detected by weekly
      antigenemia or polymerase chain reaction (PCR) in blood leukocytes, were
      randomized to intravenous therapy for 2 weeks with either foscarnet at 60 mg/kg
      or ganciclovir at 5 mg/kg administered every 12 hours; if CMV infection remained
      detectable, patients received an additional 2 weeks of intravenous foscarnet at
      90 mg/kg or ganciclovir at 6 mg/kg given once daily for 5 days per week, after
      which therapy was stopped. Primary efficacy endpoint was the occurrence of CMV
      disease or death from any cause within 180 days after SCT. A total of 213
      patients were treated with either foscarnet (n = 110) or ganciclovir (n = 103).
      Kaplan-Meier estimates of event-free survival within 180 days after SCT were
      similar in the 2 treatment groups (P =.6). During study treatment, severe
      neutropenia (< 0.5 x 10(9)/L) occurred in 11 (11%) patients on ganciclovir versus
      4 (4%) patients on foscarnet (P =.04), and impaired renal function was observed
      in 5 (5%) patients on foscarnet versus 2 (2%) patients on ganciclovir (P =.4).
      Neutropenia or thrombocytopenia required discontinuation of ganciclovir in 6 (6%)
      patients but in no foscarnet-treated patient (P =.03). After allogeneic SCT,
      preemptive therapy of CMV infection with foscarnet shows similar efficacy as with
      ganciclovir, but is associated with a lower proportion of patients who develop
      severe neutropenia and who require discontinuation of antiviral therapy due to
      hematotoxicity.

PMID- 11830462
TI  - Retrovirus-mediated gene transfer in primary T lymphocytes impairs their anti
      Epstein-Barr virus potential through both culture-dependent and selection process
      dependent mechanisms.
AB  - To modulate alloreactivity after hematopoietic stem cell transplantation, suicide
      gene-expressing donor T cells can be administered with an allogeneic T-cell
      depleted bone marrow graft. Immune competence of such cells is a critical issue.
      The impact of the ex vivo gene transfer protocol (12-day culture period including
      CD3/interleukin-2 [IL-2] activation, retroviral-mediated gene transfer, and G418
      based selection) on the anti-Epstein-Barr virus (EBV) potential of gene-modified
      cells has been examined. Cytotoxic (pCTL) and helper (pTh) cell precursor
      limiting dilution assays, interferon-gamma enzyme-linked immunospot, or
      fluorescence-activated cell sorter analysis after tetrameric HLA-A2/EBV peptide
      complexes revealed that the frequency of anti-EBV T cells was lower in gene
      modified cells (GMCs) than in similarly cultured but untransduced T cells and was
      even lower than in fresh peripheral blood mononuclear cells, demonstrating both
      an effect of the culture and of the transduction or selection. The culture
      dependent loss of EBV-reactive cells resulted from the preferential induction of
      activation-induced cell death in tetramer(+) cells. Replacing the initial CD3/IL
      2 activation by CD3/CD28/IL-2 partially restored the anti-EBV response of GMCs by
      reducing the initial activation-induced cell death and enhancing the
      proliferation of EBV-tetramer(+) cells. Moreover, the G418 selection, and not the
      transduction, was directly toxic to transduced tetramer(+) cells. Replacing the
      G418 selection by an immunomagnetic selection significantly prevented the
      selection-dependent loss of EBV-specific cells. Overall, ex vivo gene
      modification of primary T cells can result in a significant reduction in EBV
      reactive T cells through both culture-dependent and selection-dependent
      mechanisms. Improving immune functions of GMCs through modifications of the cell
      culture conditions and transduction/selection processes is critical for further
      clinical studies.

PMID- 11830463
TI  - Requirement for mitogen-activated protein kinase activation in the response of
      embryonic stem cell-derived hematopoietic cells to thrombopoietin in vitro.
AB  - Enforced expression of c-mpl in embryonic stem (ES) cells inactivated for this
      gene results in protein expression in all the ES cell progeny, producing cells
      that do not belong to the megakaryocytic lineage and are responsive to PEG
      rhuMGDF, a truncated form of human thrombopoietin (TPO) conjugated to
      polyethylene glycol. These include a primitive cell called BL-CFC, thought to
      represent the equivalent of the hemangioblast, and all myeloid progenitor cells.
      In this model, PEG-rhuMGDF was able to potentiate the stimulating effects of
      other growth factors, including vascular endothelial growth factor, on BL-CFC and
      a combination of cytokines on the growth of granulocyte macrophage-colony-forming
      units. The importance of the C-terminal domain of Mpl and of mitogen-activated
      protein kinase (MAPK) activation in TPO-dependent megakaryocytic differentiation
      has been well studied in vitro. Here, the role of this domain and the involvement
      of MAPK in upstream and nonmegakaryocytic cells are examined by using 2 truncated
      mutants of Mpl (Delta34, deletion of residues 71 to 121 in the C-terminal domain;
      and Delta3, deletion of residues 71-94) and specific inhibitors of the MAPK
      pathway. The 2 deleted regions support different functions, mediated by different
      signals. Residues 71 to 121 were required for PEG-rhuMGDF-dependent growth of BL
      CFC, for megakaryocytic and other myeloid progenitors, and for megakaryocyte
      polyploidization. These responses were mediated by the ERK1-ERK2 MAPK pathway. In
      contrast, the only function of the sequence comprising residues 71 to 94 was to
      mediate the synergistic effects of PEG-rhuMGDF with other hematopoietic growth
      factors. This function is not mediated by MAPK activation.

PMID- 11830464
TI  - Stromal cell lines from mouse aorta-gonads-mesonephros subregions are potent
      supporters of hematopoietic stem cell activity.
AB  - The aorta-gonads-mesonephros (AGM) region autonomously generates the first adult
      repopulating hematopoietic stem cells (HSCs) in the mouse embryo. HSC activity is
      initially localized to the dorsal aorta and mesenchyme (AM) and vitelline and
      umbilical arteries. Thereafter, HSC activity is found in the urogenital ridges
      (UGs), yolk sac, and liver. As increasing numbers of HSCs are generated, it is
      thought that these sites provide supportive microenvironments in which HSCs are
      harbored until the bone marrow microenvironment is established. However, little
      is known about the supportive cells within these midgestational sites, and
      particularly which microenvironment is most supportive for HSC growth and
      maintenance. Thus, to better understand the cells and molecules involved in
      hematopoietic support in the midgestation embryo, more than 100 stromal cell
      lines and clones were established from these sites. Numerous stromal clones were
      found to maintain hematopoietic progenitors and HSCs to a similar degree as, or
      better than, previously described murine stromal lines. Both the AM and UG
      subregions of the AGM produced many supportive clones, with the most highly HSC
      supportive clone being derived from the UGs. Interestingly, the liver at this
      stage yielded only few supportive stromal clones. These results strongly suggest
      that during midgestation, not only the AM but also the UG subregion provides a
      potent microenvironment for growth and maintenance of the first HSCs.

PMID- 11830465
TI  - Cultivation of aorta-gonad-mesonephros-derived hematopoietic stem cells in the
      fetal liver microenvironment amplifies long-term repopulating activity and
      enhances engraftment to the bone marrow.
AB  - During mammalian development, definitive hematopoietic stem cells (HSCs) arise in
      the aorta-gonad-mesonephros (AGM) region and colonize the fetal liver (FL) before
      hematopoiesis occurs in the bone marrow. The FL is a unique hematopoietic organ
      where both HSCs and mature blood cells are actively generated along with
      functional maturation of hepatic cells as a metabolic organ. To characterize HSCs
      and FL microenvironments during development, this study establishes a coculture
      system composed of AGM-originated HSCs and FL nonhematopoietic cells. The results
      demonstrate that FL cells support significant expansion of lineage-committed
      hematopoietic cells as well as immature progenitors. More important, long-term
      repopulating activity was amplified from AGM-originated HSCs in this coculture
      system. Engraftment of HSCs to the bone marrow was strongly enhanced by
      coculture. In addition, AGM HSCs produced significantly more hematopoietic cells
      than E14.5 and E18.5 FL HSCs in vitro. These results suggest that the FL
      microenvironment not only stimulates expansion of the hematopoietic system, but
      also possibly modifies the characteristics of AGM HSCs. Thus, this coculture
      system recapitulates the developmental process of HSCs and the FL
      microenvironment and provides a novel means to study the development of
      hematopoiesis.

PMID- 11830466
TI  - HOX-A10 regulates hematopoietic lineage commitment: evidence for a monocyte
      specific transcription factor.
AB  - Homeobox genes are well known for their crucial role during embryogenesis but
      have also been found to be critically involved in normal and leukemic
      hematopoiesis. Because most previous studies focused on the role of aberrant HOX
      gene expression in leukemogenesis and because HOX-A10 is expressed in human
      CD34(+) precursor cells, this study investigated whether HOX-A10 also plays a
      pivotal role in normal hematopoietic-lineage determination. The effect of
      enforced expression of this transcription factor on hematopoietic differentiation
      of highly purified human cord-blood progenitors was examined by using in vitro
      assays. In fetal thymic organ cultures, a dramatic reduction in cells expressing
      high levels of HOX-A10 was observed, along with absence of thymocytes positive
      for CD3(+) T-cell receptor alphabeta. Furthermore, in MS-5 stromal cell cultures,
      there was a 7-fold reduction in the number of natural killer cells and a 9-fold
      reduction in the number of B cells, thus showing a profound defect in
      differentiation toward the lymphoid lineage in HOX-A10-transduced progenitors. In
      contrast, the number of CD14(+) monocytic cells in the stromal cell culture was 6
      fold higher, suggesting an enhanced differentiation toward the myeloid
      differentiation pathway of HOX-A10-transduced progenitors. However, there was a
      slight reduction in the number of CD15(+) granulocytic cells, which were blocked
      in their final maturation. These data show that HOX-A10 can act as an important
      key regulator of lineage determination in human hematopoietic progenitor cells.

PMID- 11830467
TI  - A functional platelet fibrinogen receptor with a deletion in the cysteine-rich
      repeat region of the beta(3) integrin: the Oe(a) alloantigen in neonatal
      alloimmune thrombocytopenia.
AB  - This report describes a new low-frequency alloantigen, Oe(a), responsible for a
      case of neonatal alloimmune thrombocytopenia (NAIT). In a population study none
      of 600 unrelated blood donors was an Oe(a) carrier. By immunochemical studies the
      Oe(a) antigen could be assigned to platelet glycoprotein (GP) IIIa. Sequencing of
      GPIIIa complementary DNA from an Oe(a) (+) individual showed deletion of a lysine
      residue at position 611 (DeltaLys(611)). Analysis of 20 Oe(a) (-) and 3 Oe(a) (+)
      individuals showed that the DeltaLys(611) form of GPIIIa was related to the
      phenotype. Anti-Oe(a) reacted with the DeltaLys(611), but not with the wild-type
      isoforms on stable transfectants expressing GPIIIa, indicating that DeltaLys(611)
      directly induces the expression of Oe(a) epitopes. Under nonreducing conditions
      the Pro(33)DeltaLys(611) variant migrated with a slightly decreased molecular
      weight compared to the Pro(33)Lys(611) isoform suggesting that DeltaLys(611) has
      an influence on the disulfide bonds of GPIIIa. The Pro(33)DeltaLys(611) GPIIIa
      could undergo conformational changes and bind to fibrinogen in a similar manner
      as the Pro(33)Lys(611) isoform. No difference was found in the tyrosine
      phosphorylation of pp125(FAK), suggesting that DeltaLys(611) has no effect on
      integrin function. In contrast to all other low-frequency antigens, the
      DeltaLys(611) isoform was associated with the HPA-1b, but not with the high
      frequency HPA-1a allele. Comparison with GPIIIa DNA from nonhuman primates
      indicated that the HPA-1a allele represents the ancestral form of GPIIIa. It can
      be assumed that the Oe(a) form did arise as a result of a mutational event from
      an already mutated GPIIIa allele.

PMID- 11830468
TI  - 3-Dimensional structure of membrane-bound coagulation factor VIII: modeling of
      the factor VIII heterodimer within a 3-dimensional density map derived by
      electron crystallography.
AB  - Despite recent studies, the organization of coagulation factor VIII (FVIII) on a
      phospholipid (PL) membrane is not known in detail. Thus, 2-dimensional (2D)
      crystals of human FVIII lacking the B domain were prepared for electron
      microscopy onto negatively charged PL monolayers. The 3-dimensional (3D) density
      map of the PL-bound FVIII protein was calculated at 1.5 nm. Existing atomic data
      and models for FVIII domains were fitted unambiguously within the 3D density map
      of the molecule. FVIII domains arrangement followed a compact spiral organization
      with the A3 domains in close association with the C1 and C2 domains near the PL
      surface. Viewed toward the membrane the A domains' heterotrimer is oriented side
      on with the pseudo-3-fold axis almost parallel to the PL surface and A1 fully
      covering C1. The C2 domain is partially overlapped by the A2 domain of an
      adjacent molecule in the 2D crystal, favoring close packing. Viewed parallel to
      the membrane, C2 is slightly inclined to the PL surface covering an area of 12
      nm(2). Four C2 loops are embedded within the lipid monolayer at about 0.7 to 1.0
      nm depth. C1 forms almost a right angle with C2, its long axis nearly parallel to
      the membrane. The proposed structure for membrane-bound FVIII results from
      modeling of the FVIII domains within a 3D density map obtained from electron
      crystallography and accords with the main biochemical and structural information
      known to date. A model is proposed for FVIIIa and factor IXa assembly within the
      membrane-bound factor X-activating complex. (Blood. 2002;99:1215-1223)

PMID- 11830469
TI  - Adhesion of human platelets to serum amyloid A.
AB  - Serum amyloid A (SAA) is an acute phase reactant, and its level in the blood is
      elevated to 1000-fold in response of the body to trauma, infection, inflammation,
      and neoplasia. SAA was reported to inhibit platelet aggregation and to induce
      adhesion of leukocytes. This study looked at adhesion of human platelets to SAA.
      Immobilized SAA supported the adhesion of human washed platelets; level of
      adhesion to SAA was comparable to fibronectin and lower than to fibrinogen.
      Adhesion to SAA was further enhanced by Mn(2+) and the physiological agonist,
      thrombin. Platelet adhesion to SAA was completely abolished by anti-SAA antibody.
      SAA-induced adhesion was inhibited by antibodies against the integrin receptor
      alphaIIbbeta3, by the peptide GRGDSP and by SAA-derived peptide containing YIGSR
      like and RGD-like adhesion motifs (amino acids 29 to 42). Adhesion was not
      inhibited by control immunoglobulin G, by antibody against the integrin receptor
      alphaVbeta3, by the peptide GRGESP, and by SAA-derived peptide that includes
      incomplete RGD motif. SAA-derived peptide 29 to 42 also inhibited platelet
      adhesion to fibronectin. Transfected human melanoma cells expressing
      alphaIIbbeta3 adhered to SAA, whereas transfected cells expressing alphaVbeta3
      did not. By using flow cytometry, the alphaIIbbeta3 cells displayed significantly
      higher levels of binding of soluble SAA than the alphaVbeta3 cells. These data
      indicate that human platelets specifically adhere to SAA in an RGD- and
      alphaIIbbeta3-dependent manner. Thus, SAA may play a role in modulating platelet
      adhesion at vascular injury sites by sharing platelet receptors with other
      platelet-adhesive proteins.

PMID- 11830471
TI  - The role of CC chemokine receptor 5 in antiviral immunity.
AB  - The CC chemokine receptor CCR5 is an important coreceptor for human
      immunodeficiency virus (HIV), and there is a major thrust to develop anti-CCR5
      based therapies for HIV-1. However, it is not known whether CCR5 is critical for
      a normal antiviral T-cell response. This study investigated the immune response
      to lymphocytic choriomeningitis virus in mice lacking CCR5 (CCR5(-/-) mice). This
      infection is a classical model for studying antiviral immunity, and influx of
      CCR5-expressing CD8(+) T cells and macrophages is essential for both virus
      control and associated immunopathology. Results showed that the virus-induced
      clonal expansion of antigen-specific T cells was augmented in CCR5(-/-) mice
      especially with regard to the CD4(+) subset. Despite absence of CCR5,
      intracerebral infection invariably resulted in lethal T cell-mediated meningitis,
      and quantitative and qualitative analysis of the inflammatory exudate cells did
      not reveal any significant differences between gene-targeted mice and wild-type
      controls. CCR5 was also found to be redundant regarding the ability to eliminate
      virus from internal organs. Using delayed-type hypersensitivity to evaluate
      CD8(+) T cell-mediated inflammation, no significant influence of CCR5 was found,
      not even when viral peptide was used as local trigger instead of live virus.
      Finally, long-term CD8(+) T cell-mediated immune surveillance was efficiently
      sustained in CCR5(-/-) mice. Taken together, these results indicate that
      expression of CCR5 is not critical for T cell-mediated antiviral immunity, and
      this molecule may therefore constitute a logic and safe target for anti-HIV
      therapies.

PMID- 11830470
TI  - Defining a second epitope for heparin-induced thrombocytopenia/thrombosis
      antibodies using KKO, a murine HIT-like monoclonal antibody.
AB  - Heparin-induced thrombocytopenia/thrombosis (HIT/T) is a common complication of
      heparin therapy that is caused by antibodies to platelet factor 4 (PF4) complexed
      with heparin. The immune response is polyclonal and polyspecific, ie, more than
      one neoepitope on PF4 is recognized by HIT/T antibodies. One such epitope has
      been previously identified; it involves the domain between the third and fourth
      cysteine residues in PF4 (site 1). However, the binding sites for other HIT/T
      antibodies remain to be defined. To explore this issue, the binding site of KKO,
      an HIT/T-like murine monoclonal antibody, was defined. KKO shares a binding site
      with many HIT/T antibodies on PF4/heparin, but does not bind to site 1 or
      recognize mouse PF4/heparin. Therefore, the binding of KKO to a series of
      mouse/human PF4 chimeras complexed with heparin was examined. KKO recognizes a
      site that requires both the N terminus of PF4 and Pro34, which immediately
      precedes the third cysteine. Both regions lie on the surface of the PF4 tetramer
      in sufficient proximity (within 0.74 nm) to form a contiguous antigenic
      determinant. The 10 of 14 HIT/T sera that require the N terminus of PF4 for
      antigen recognition also require Pro34 to bind. This epitope, termed site 2, lies
      adjacent to site 1 in the crystal structure of the PF4 tetramer. Yet sites 1 and
      2 can be recognized by distinct populations of antibodies. These studies further
      help to define a portion of the PF4 tetramer to which self-reactive antibodies
      develop in patients exposed to heparin.

PMID- 11830472
TI  - Reduced tissue macrophage population in the lung by anticancer agent
      cyclophosphamide: restoration by local granulocyte macrophage-colony-stimulating
      factor gene transfer.
AB  - Granulocytopenia is thought to be the sole mechanism underlying the increased
      susceptibility to bacterial infection in hosts with anticancer chemotherapy.
      Little is known about the functional state of tissue macrophage populations in
      such hosts. Using a model of chemotherapy-induced leukopenia, the number and
      function of alveolar macrophages (AMS) were examined during and after multiple
      injections of an anticancer agent, cyclophosphamide (CP). Although CP quickly
      reduced peripheral blood leukocytes, the number of these cells rebounded quickly
      3 to 4 days after the withdrawal of CP. Accompanying blood leukopenia was a
      profound reduction in the number of AMs. Contrary to the rapid onset of blood
      leukopenia, tissue macrophage deficiency was a more chronic process that worsened
      gradually as the CP regimen continued. Of importance, in contrast to blood
      leukopenia, which restored itself shortly after CP withdrawal, tissue macrophage
      deficiency was not immediately self-recoverable in spite of a restored number of
      circulating leukocytes. Although AMS had a decreased ability to proliferate
      during, but not after, the CP regimen, these cells retained a normal ability to
      release tumor necrosis factor-alpha and nitric oxide. To identify the potential
      therapeutics for recovering macrophages, a gene vector expressing granulocyte
      macrophage-colony-stimulating factor (GM-CSF) was delivered either systemically
      or locally. GM-CSF transgene was able to expand macrophage populations only when
      delivered to the lung after, but not during, the CP regimen. This study thus
      identifies tissue macrophage deficiency as a mechanism of weakened innate
      immunity by chemotherapy and suggests the usefulness of topical GM-CSF transgene
      expression for restoring innate immunity in the lung.

PMID- 11830473
TI  - Precise quantification of minimal residual disease at day 29 allows
      identification of children with acute lymphoblastic leukemia and an excellent
      outcome.
AB  - The postinduction level of minimal residual disease (MRD) was quantified with a
      competitive polymerase chain reaction (PCR) technique in 104 children with acute
      lymphoblastic leukemia (ALL) diagnosed between June 1993 and January 1998 and
      followed for a median of 4.2 years. A significant correlation was found between
      the MRD level on day 15 (D15) and day 29 (D29) after the start of induction
      therapy (r(s) = 0.70, P <.0001). The 15 patients with T-cell disease had higher
      D29 MRD than those with B-lineage ALL (P =.01). Age was positively related to D29
      MRD (r(s) = 0.32, P =.001). The 16 patients who had a relapse had higher D15 and
      D29 MRD levels than the patients who stayed in remission (median levels D15, 1%
      versus 0.1%, P =.03; D29, 0.4% versus 0.01%, P =.0001). No patients with a MRD
      level less than 0.01% on D29 have so far had a relapse, whereas the 7-year
      probability of event-free survival for patients with higher MRD levels was 0.52
      (P =.0007). The group of patients with a D29 MRD less than 0.01% included
      patients with T-cell disease, white blood cell count more than 50 x 10(9)/L at
      diagnosis, or age 10 years or older, and could not be identified by up-front
      criteria. The best-fit Cox model to predict the risk of relapse included D29 MRD
      (P =.004) and age (P =.009). These findings indicate that with the present
      treatment protocol MRD quantification at an early stage of therapy identifies
      patients with a very low risk of relapse. Further trials are needed to reveal
      whether such patients with D29 MRD less than 0.01% can be cured with less
      intensive chemotherapy, which would reduce the risk of serious late effects as
      well as the costs of therapy.

PMID- 11830474
TI  - Sequential production of interferon-gamma by NK1.1(+) T cells and natural killer
      cells is essential for the antimetastatic effect of alpha-galactosylceramide.
AB  - The antimetastatic effect of the CD1d-binding glycolipid, alpha
      galactosylceramide (alpha-GalCer), is mediated by NK1.1(+)T (NKT) cells; however,
      the mechanisms behind this process are poorly defined. Although it has been shown
      to involve NK cells and interferon-gamma (IFN-gamma) production, the way these
      factors collaborate to mediate effective tumor rejection and the importance of
      other factors characteristic of NKT cell and NK cell activation are unknown.
      Using gene-targeted mice and antibody treatments, the critical need for
      interleukin 12 (IL-12), IFN-gamma, and NK cells has been shown in the
      antimetastatic activity of alpha-GalCer in the lungs and the liver. By contrast,
      in lung and liver metastasis models, cytotoxic molecules expressed by NK cells
      and NKT cells (perforin, Fas ligand, and tumor necrosis factor-related apoptosis
      inducing ligand) and an NKT cell-secreted cytokine, IL-4, were not necessary for
      the antitumor activity of alpha-GalCer. Like IL-12, IL-18 was required for
      optimal serum IFN-gamma induction and control of lung metastases by alpha-GalCer.
      IL-18 was unnecessary for alpha-GalCer-related suppression of liver metastases.
      Most importantly, after adoptive transfer of alpha-GalCer-reactive NKT cells or
      NK cells into NKT cell-deficient, IFN-gamma-deficient, or RAG-1-deficient mice,
      it was demonstrated that the sequential production of IFN-gamma by NKT cells and
      NK cells was absolutely required to reconstitute the antimetastatic activity of
      alpha-GalCer.

PMID- 11830475
TI  - Functional in vivo characterization of human monoclonal anti-D in NOD-scid mice.
AB  - The prophylaxis of the hemolytic disease of the newborn requires significant
      amounts of plasma-derived polyclonal human anti-D. Because of procurement
      problems, there is a growing interest in replacing plasma-derived anti-D by in
      vitro-produced human monoclonal anti-D. Hundreds of monoclonal anti-D have been
      prepared, but the selection of the most potent for in vivo use is difficult
      because it cannot be predicted by in vitro characterization. This study evaluated
      the possibility of using nonobese diabetic/severe combined immunodeficient (NOD
      scid) mice for the in vivo evaluation of human monoclonal anti-D. Human red blood
      cells (RBCs) were found to circulate normally in the blood of NOD-scid mice
      previously injected with a physiologic amount of human immunoglobulin G (10 mg).
      The addition of a small amount of anti-D (1 to 5 microg) resulted in the
      clearance of Rh D(+) RBCs within 4 hours. The comparative testing of 8 monoclonal
      anti-Ds showed a wide range of potency (15% to 87%) relative to plasma-derived
      polyclonal anti-D. There was no strong correlation between the in vivo potency
      index and the immunoglobulin G isotype, affinity, or fine specificity of the
      antibodies. These results show the usefulness of NOD-scid mice for the initial in
      vivo screening of human monoclonal anti-D before testing the most active
      antibodies in clinical trials done in human volunteers.

PMID- 11830476
TI  - Expression of type 1 (interferon gamma) and type 2 (interleukin-13, interleukin
      5) cytokines at distinct stages of natural killer cell differentiation from
      progenitor cells.
AB  - To determine whether production of type 1 and type 2 cytokines defines discrete
      stages of natural killer (NK) cell differentiation, cytokine expression was
      analyzed in human NK cells generated in vitro in the presence of interleukin-15
      (IL-15) and/or IL-2 from umbilical cord blood hematopoietic progenitors. Like
      peripheral NK cells, the CD161(+)/CD56(+) NK cells from these cultures contained
      a tumor necrosis factor alpha (TNF-alpha)(+)/granulocyte macrophage-colony
      stimulating factor (GM-CSF)(+) subset, an interferon gamma (IFN-gamma)(+) subset,
      mostly included within the former, and very few IFN-gamma(-)/IL-13(+) cells.
      Instead, most immature CD161(+)/CD56(-) NK cells, detectable only in the cultures
      with IL-2, produced IL-13, TNF-alpha, and GM-CSF, but not IFN-gamma, and
      contained an IL-5(+) subset. In short-term cultures with IL-12 and feeder cells,
      a proportion of the immature cells acquired the ability to produce IFN-gamma.
      Part of these produced both IFN-gamma and IL-13, irrespective of induced CD56
      expression. These in vitro data indicate that ability to produce the type 2
      cytokines IL-13 and IL-5 defines CD161(+) NK cells at intermediate stages of
      differentiation, and is lost upon terminal functional differentiation,
      concomitant with acquired ability to produce IFN-gamma.

PMID- 11830477
TI  - Dramatic increase in lymph node dendritic cell number during infection by the
      mouse mammary tumor virus occurs by a CD62L-dependent blood-borne DC recruitment.
AB  - Despite the information dealing with the differential phenotype and function of
      the main mouse dendritic cell (DC) subpopulations, namely, CD8alpha(-) and
      CD8alpha(+) DCs, their origin and involvement in antiviral immune responses in
      vivo are still largely unknown. To address these issues, this study used the
      changes occurring in DC subpopulations during the experimental infection by the
      Swiss (SW) strain of the mouse mammary tumor virus (MMTV). MMTV(SW) induced an 18
      fold increase in lymph node DCs, which can be blocked by anti-CD62L treatment,
      concomitant with the presence of high numbers of DCs in the outer cortex, in
      close association with high endothelial venules. These data suggest that the DC
      increase caused by MMTV(SW) infection results from the recruitment of blood-borne
      DCs via high endothelial venules, by a CD62L-dependent mechanism. In addition,
      skin sensitization assays indicate that MMTV(SW) infection inhibits epidermal
      Langerhans cell migration to the draining lymph node. Moreover, data on the
      kinetics of MMTV(SW)-induced expansion of the different DC subsets support the
      hypothesis that CD8(-) and CD8(+) DCs represent different maturation stages of
      the same DC population, rather than myeloid- and lymphoid-derived DCs,
      respectively, as previously proposed. Finally, the fact that DCs were infected by
      MMTV(SW) suggests their participation in the early phases of infection.

PMID- 11830478
TI  - Interleukin 18 (IL-18) in synergy with IL-2 induces lethal lung injury in mice: a
      potential role for cytokines, chemokines, and natural killer cells in the
      pathogenesis of interstitial pneumonia.
AB  - Interleukin 18 (IL-18) was discovered as an interferon-gamma (IFN-gamma)-inducing
      factor and plays important roles in natural killer (NK) cell activation. IL-18
      also induces proinflammatory cytokines; chemokines; helper T-cell 2 (T(H)2)
      cytokines (eg, IL-4, IL-13); and immunoglobulin E (Ig-E) and IgG1 production. The
      combination of IL-18 plus IL-2 or IL-12 up-regulates IFN-gamma gene expression
      and NK cytotoxicity and has synergistic antitumor activity in vivo and in vitro.
      Here it is reported that daily administration of IL-18 with IL-2, but not of IL
      18 or IL-2 alone, induces lethal lung injury in normal mice, but not in IL-18
      receptor alpha (IL-1 receptor-related protein)-deficient (IL-18 receptor alpha(-/
      )) mice. Marked interstitial infiltration of lymphocytes, composed mainly of NK
      cells, was found in the lungs of IL-18/IL-2-treated mice. Increased cytokine and
      chemokine levels were observed in the sera and lungs of IL-18/IL-2-treated mice.
      Administration of IL-18/IL-2 was also lethal to mice treated with a
      metalloproteinase inhibitor, which inhibited tumor necrosis factor-alpha and Fas
      ligand release. While IFN-gamma(-/-) mice were partially resistant to the
      treatment, IL-4(-/-), IL-13(-/-), IL-4/IL-13(-/-), and Stat6(-/-) mice were
      sensitive to IL-18/IL-2, indicating that these genes were not involved in the
      host response. The lethal effect by IL-18/IL-2 was completely eliminated in
      severe combined immunodeficient mice pretreated with antiasialo-GM1 antibody and
      normal mice pretreated with anti-NK1.1 but not with anti-CD4 or anti-CD8,
      monoclonal antibody. These results suggest that specific cytokines, chemokines,
      and NK cells are involved in the pathogenesis of interstitial pneumonia. These
      results suggest that the clinical use of this interleukin may result in
      unexpected physiological consequences.

PMID- 11830479
TI  - Analysis of the IgV(H) somatic mutations in splenic marginal zone lymphoma
      defines a group of unmutated cases with frequent 7q deletion and adverse clinical
      course.
AB  - This study aimed to correlate the frequency of somatic mutations in the IgV(H)
      gene and the use of specific segments in the V(H) repertoire with the clinical
      and characteristic features of a series of 35 cases of splenic marginal zone
      lymphoma (SMZL). The cases were studied by seminested polymerase chain reaction
      by using primers from the FR1 and J(H) region. The results showed unexpected
      molecular heterogeneity in this entity, with 49% unmutated cases (less than 2%
      somatic mutations). The 7q31 deletions and a shorter overall survival were more
      frequent in this group. Additionally a high percentage (18 of 40 sequences) of
      SMZL cases showed usage of the V(H)1-2 segment, thereby emphasizing the
      singularity of this neoplasia, suggesting that this tumor derives from a highly
      selected B-cell population and encouraging the search for specific antigens that
      are pathogenically relevant in the genesis or progression of this tumor.

PMID- 11830480
TI  - Negative regulation of erythroblast maturation by Fas-L(+)/TRAIL(+) highly
      malignant plasma cells: a major pathogenetic mechanism of anemia in multiple
      myeloma.
AB  - Multiple myeloma (MM) is associated with severe normochromic/normocytic anemia.
      This study demonstrates that the abnormal up-regulation of apoptogenic receptors,
      including both Fas ligand (L) and tumor necrosis factor-related apoptosis
      inducing ligand (TRAIL), by highly malignant myeloma cells is involved in the
      pathogenesis of the ineffective erythropoiesis and chronic exhaustion of the
      erythroid matrix. By measuring Fas-L and TRAIL in plasma cells and the content of
      glycophorin A (GpA) in erythroblasts from a cohort of 28 untreated, newly
      diagnosed patients with MM and 7 with monoclonal gammopathy of undetermined
      significance (MGUS), selected in relation to their peripheral hemoglobin values,
      results showed that both receptors occurred at high levels in 15 severely anemic
      MM patients. Their marrow erythropoietic component was low and included
      predominantly immature GpA(+dim) erythroblasts, in contrast with the higher
      relative numbers of mature GpA(+bright) erythroid cells observed in the nonanemic
      patients and those with MGUS. In cocultures with autologous Fas-L(+)/TRAIL(+)
      myeloma cells, the expanded GpA(+dim) erythroid population underwent prompt
      apoptosis after direct exposure to malignant plasma cells, whereas erythroblasts
      from nonanemic patients were scarcely affected. The evidence that Fas
      L(+)/TRAIL(+) malignant plasma cells prime erythroblast apoptosis by direct
      cytotoxicity was also supported by the increase of FLICE in fresh immature
      GpA(+dim) erythroid cells, whereas ICE and caspase-10 increased in subsequent
      maturative forms. In addition, GATA-1, a survival factor for erythroid
      precursors, was remarkably down-regulated in fresh erythroblasts from the
      severely anemic patients. These results indicate that progressive destruction of
      the erythroid matrix in aggressive MM is due to cytotoxic mechanisms based on the
      up-regulation in myeloma cells of Fas-L, TRAIL, or both. It is conceivable that
      the altered regulation of these receptors defines a peculiar cytotoxic phenotype
      that drives the progression of aggressive MM.

PMID- 11830481
TI  - The chimeric anti-CD20 antibody rituximab induces apoptosis in B-cell chronic
      lymphocytic leukemia cells through a p38 mitogen activated protein-kinase
      dependent mechanism.
AB  - Antibodies against CD20 can activate complement and induce antibody-dependent
      cellular cytotoxicity (ADCC) in B lymphocytes. In B-cell lines, such antibodies
      also induce apoptosis. In this study, the expression and function of CD20 on B
      cell chronic lymphocytic leukemia (B-CLL) cells were analyzed. Flow cytometric
      analysis demonstrated that B-CLL cells express CD20 with a fluorescence intensity
      that is significantly weaker than that of normal CD5(+) and CD5(-) B cells and
      that of malignant CD5(-) low-grade non-Hodgkin lymphoma cells. A small population
      of cells from healthy donors that have an expression pattern of CD5 and CD20
      identical to that of B-CLL cells were identified, and this population was
      confirmed to be of T lineage, not B lineage. Culture of freshly isolated B-CLL
      cells in the presence of the chimeric anti-CD20 antibody rituximab and a cross
      linking F(ab)(2) fragment, resulted in dose- and time-dependent induction of
      apoptosis. The induction of apoptosis occurred under conditions in which the
      influence of complement activation and ADCC was negligible. Cross-linking of
      rituximab induced strong and sustained phosphorylation of the 3 mitogen activated
      protein (MAP) kinases c-Jun NH2-terminal protein kinase, extracellular signal
      regulated kinase, and p38. Introduction of the p38 inhibitor SB203580 into the
      system completely blocked signaling downstream of p38, as evidenced by the
      absence of MAPKAP K2 activity, and significantly reduced the degree of anti-CD20
      induced apoptosis. These results demonstrate that cross-linking of rituximab
      bound to CD20 on freshly isolated B-CLL cells induces apoptosis through a
      signaling pathway that is dependent on p38 MAP-kinase activation.

PMID- 11830482
TI  - Sensitization of B-cell chronic lymphocytic leukemia cells to recombinant
      immunotoxin by immunostimulatory phosphorothioate oligodeoxynucleotides.
AB  - A recombinant anti-CD25 immunotoxin, LMB-2, has shown clinical efficacy in hairy
      cell leukemia and T-cell neoplasms. Its activity in B-cell chronic lymphocytic
      leukemia (B-CLL) is inferior but might be improved if B-CLL cells expressed
      higher numbers of CD25 binding sites. It was recently reported that DSP30, a
      phosphorothioate CpG-oligodeoxynucleotide (CpG-ODN) induces immunogenicity of B
      CLL cells by up-regulation of CD25 and other antigens. The present study
      investigated the antitumor activity of LMB-2 in the presence of DSP30. To this
      end, B-CLL cells from peripheral blood of patients were isolated
      immunomagnetically to more than 98% purity. Incubation with DSP30 for 48 hours
      augmented CD25 expression in 14 of 15 B-CLL samples, as assessed by flow
      cytometry. DSP30 increased LMB-2 cytotoxicity dose dependently whereas a control
      ODN with no CpG motif did not. LMB-2 displayed no antitumor cell activity in the
      absence of CpG-ODN as determined colorimetrically with an (3-(4,5-dimethylthiazol
      2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt
      (MTS) assay. In contrast, B-CLL growth was inhibited in 12 of 13 samples with 50%
      inhibition concentrations (IC(50)) in the range of LMB-2 plasma levels achieved
      in clinical studies. Two samples were not evaluable because of spontaneous B-CLL
      cell death in the presence of DSP30. Control experiments with an immunotoxin that
      does not recognize hematopoietic cells, and an anti-CD22 immunotoxin, confirmed
      that sensitization to LMB-2 was specifically due to up-regulation of CD25. LMB-2
      was much less toxic to normal B and T lymphocytes compared with B-CLL cells. In
      summary, immunostimulatory CpG-ODNs efficiently sensitize B-CLL cells to a
      recombinant immunotoxin by modulation of its target. This new treatment strategy
      deserves further attention.

PMID- 11830483
TI  - Impact of the lymphoma idiotype on in vivo tumor protection in a vaccination
      model based on targeting antigens to antigen-presenting cells.
AB  - Trioma cell vaccination is a potent new immunologic approach for the therapy of
      malignant B-cell lymphoma. It is based on targeting tumor antigens to
      internalizing receptors on antigen-presenting cells (APCs). Tumor cells are fused
      to an APC-specific hybridoma, where they are converted to trioma cells that
      include potentially all lymphoma-derived antigens and that express the APC
      binding arm. In this study, the mechanisms of trioma-mediated tumor immunity in
      immunocompetent mice were dissected, and it was shown in this model system that
      humoral anti-idiotypic immunity is indeed detectable after idiotype-specific
      immunization but that it does not reflect the degree of tumor protection obtained
      in vivo. Immunization against the idiotype alone was not sufficient for efficient
      tumor rejection in vivo. Targeting tumor antigens to APCs is only successful in
      terms of inducing tumor protection when designed as a polyvalent vaccination
      protocol.

PMID- 11830484
TI  - Mutations in the gene encoding the transcription factor CCAAT/enhancer binding
      protein alpha in myelodysplastic syndromes and acute myeloid leukemias.
AB  - The CCAAT/enhancer binding protein alpha (C/EBPalpha) protein is essential for
      proper lung and liver function and granulocytic and adipose tissue
      differentation. It was hypothesized that abnormalties in C/EBPalpha function
      contribute to the development of malignancies in a variety of tissues. To test
      this, genomic DNA from 408 patient samples and 5 cell lines representing 11
      different cancers was screened for mutations in the C/EBPalpha gene. Two silent
      polymorphisms termed P1 and P2 were present at frequencies of 13.5% and 2.2%,
      respectively. Of the 12 mutations detected in 10 patients, silent changes were
      identified in one nonsmall cell lung cancer, one prostate cancer, and one acute
      myelogenous leukemia (AML) subtype M4. The 9 remaining mutations were detected in
      1 of 92 (1.1%) myelodysplastic syndrome (MDS) samples and 6 of 78 (7.7%) AML (AML
      M2 and AML-M4) samples. Some mutations truncated the predicted protein with loss
      of the DNA-binding (basic region) and dimerization (leucine zipper [ZIP]) domains
      by either deletions or nonsense codons. Also, inframe deletions or insertions in
      the fork region located between the leucine zipper and basic region, or within
      the leucine zipper, disrupted the alpha-helical phase of the bZIP domain. The
      inframe deletion and insertion mutations abrogated the transcriptional activation
      function of C/EBPalpha on the granulocyte colony-stimulating factor receptor
      promoter. These mutants localized properly to the nucleus, but were unable to
      bind to the C/EBP site in the promoter and did not possess dominant-negative
      activity. The mutations in the MDS patient and one AML-M2 patient were biallelic,
      indicating a loss of C/EBPalpha function. These results suggest that mutation of
      C/EBPalpha is involved in specific subtypes of AML and in MDS, but may occur
      rarely in other types of leukemias or nonhematologic malignancies.

PMID- 11830485
TI  - Human T-cell leukemia virus type I Tax transactivates the matrix
      metalloproteinase-9 gene: potential role in mediating adult T-cell leukemia
      invasiveness.
AB  - Human T-cell leukemia virus type I (HTLV-I) is the etiologic agent of adult T
      cell leukemia (ATL) and of tropical spastic paraparesis/HTLV-I-associated
      myelopathy. Infiltration of various tissues by circulating leukemic cells is a
      characteristic of ATL. Matrix metalloproteinases (MMPs), which mediate the
      degradation of the basement membrane and extracellular matrix, play an important
      role in metastasis and tumor cell dissemination. The aim of this study was to
      explore whether expression of MMP-2 and MMP-9 was deregulated by HTLV-I
      infection. The data showed that HTLV-I-infected T-cell lines expressed high
      levels of MMP-9 compared with uninfected T-cell lines. In contrast, the levels of
      the related MMP-2 were not significantly altered by HTLV-I infection. In
      addition, the elevated expression of MMP-9 in HTLV-I-infected cells was
      attributable to the action of the viral transactivator protein Tax. The results
      show that Tax can activate the MMP-9 promoter and induce MMP-9 expression in T
      cells, indicating that the constitutive expression of MMP-9 in virus-infected
      cell lines is at least in part mediated by Tax. Activation of the MMP-9 promoter
      by Tax occurs mainly through the action of NF-kappaB and SP-1. The biologic
      significance of these observations was validated by the following 2 findings: MMP
      9 expression was increased in primary ATL cells, and plasma MMP-9 levels were
      elevated in ATL patients. In addition, plasma levels of MMP-9 correlated with
      organ involvement in ATL patients. Together these data suggest that
      overexpression of MMP-9 in HTLV-I- infected cells may be in part responsible for
      the invasiveness of ATL cells.

PMID- 11830486
TI  - High frequency of Ikaros isoform 6 expression in acute myelomonocytic and
      monocytic leukemias: implications for up-regulation of the antiapoptotic protein
      Bcl-XL in leukemogenesis.
AB  - While studying Ikaros proteins in childhood acute myeloid leukemia (AML), Ikaros
      isoform 6 (Ik6) expression was detected in 7 of 10 cases of M4 and M5 leukemia,
      but in none of the remaining French-American-British subtypes (M2, 8 cases; M7, 6
      cases). The spliced Ikaros isoforms 4 to 8 (Ik4-8) suppress the function of full
      length Ik1 or Ik2 in a dominant-negative manner, owing to their reduced numbers
      of DNA binding sites. Thus, dominant-negative Ikaros isoforms may inhibit the
      normal transcriptional regulation of hematopoietic cell development. To clarify
      the function of Ik6 in developing blood cells, this isoform was transiently
      transfected into an Ik2(+), interleukin-3 (IL-3)-dependent 32D murine myeloid
      precursor cell line and studied the expression of Bcl-2 family proteins in
      relation to in vitro cell growth, using a tetracycline-inducible TREx system. The
      possibility of aberrant cell regulation due to Ikaros functional changes was
      examined by cotransfecting both Ik2 and Ik6 into Ikaros/Aiolos/Helios triple
      negative Cos-7 cells. The results demonstrated IL-3-independent growth by Ik6
      transfected 32D clones coincident with up-regulation of the antiapoptotic protein
      Bcl-XL. Up-regulation of Bcl-XL, but not of other Bcl-2 family proteins, was
      associated with the suppression of functional Ik2 by Ik6 in a dominant-negative
      fashion. Thus, the pathogenesis of myelomonocytic/monocytic AML may involve
      aberrant regulation of apoptosis due to unscheduled expression of the Ik6
      isoform.

PMID- 11830487
TI  - Frequent mutations in the ligand-binding domain of PML-RARalpha after multiple
      relapses of acute promyelocytic leukemia: analysis for functional relationship to
      response to all-trans retinoic acid and histone deacetylase inhibitors in vitro
      and in vivo.
AB  - This study identified missense mutations in the ligand binding domain of the
      oncoprotein PML-RARalpha in 5 of 8 patients with acute promyelocytic leukemia
      (APL) with 2 or more relapses and 2 or more previous courses of all-trans
      retinoic acid (RA)-containing therapy. Four mutations were novel (Lys207Asn,
      Gly289Arg, Arg294Trp, and Pro407Ser), whereas one had been previously identified
      (Arg272Gln; normal RARalpha1 codon assignment). Five patients were treated with
      repeat RA plus phenylbutyrate (PB), a histone deacetylase inhibitor, and one
      patient experienced a prolonged clinical remission. Of the 5 RA + PB-treated
      patients, 4 had PML-RARalpha mutations. The Gly289Arg mutation in the clinical
      responder produced the most defective PML-RARalpha function in the presence of RA
      with or without sodium butyrate (NaB) or trichostatin A. Relapse APL cells from
      this patient failed to differentiate in response to RA but partially
      differentiated in response to NaB alone, which was augmented by RA. In contrast,
      NaB alone had no differentiation effect on APL cells from another mutant case
      (Pro407Ser) but enhanced differentiation induced by RA. These results indicate
      that PML-RARalpha mutations occurred with high frequency after multiple RA
      treatment relapses, indicate that the functional potential of PML-RARalpha was
      not correlated with clinical response to RA + PB treatment, and suggest that the
      response to RA + PB therapy in one patient was related to the ability of PB to
      circumvent the blocked RA-regulated gene response pathway.

PMID- 11830488
TI  - In vitro analyses of known and novel RUNX1/AML1 mutations in dominant familial
      platelet disorder with predisposition to acute myelogenous leukemia: implications
      for mechanisms of pathogenesis.
AB  - Familial platelet disorder with predisposition to acute myelogenous leukemia
      (FPD/AML) is an autosomal dominant familial platelet disorder characterized by
      thrombocytopenia and a propensity to develop AML. Mutation analyses of RUNX1 in 3
      families with FPD/AML showing linkage to chromosome 21q22.1 revealed 3 novel
      heterozygous point mutations (K83E, R135fsX177 (IVS4 + 3delA), and Y260X).
      Functional investigations of the 7 FPD/AML RUNX1 Runt domain point mutations
      described to date (2 frameshift, 2 nonsense, and 3 missense mutations) were
      performed. Consistent with the position of the mutations in the Runt domain at
      the RUNX1-DNA interface, DNA binding of all mutant RUNX1 proteins was absent or
      significantly decreased. In general, missense and nonsense RUNX1 proteins
      retained the ability to heterodimerize with PEBP2beta/CBFbeta and inhibited
      transactivation of a reporter gene by wild-type RUNX1. Colocalization of mutant
      RUNX1 and PEBP2beta/CBFbeta in the cytoplasm was observed. These results suggest
      that the sequestration of PEBP2beta/CBFbeta by mutant RUNX1 may cause the
      inhibitory effects. While haploinsufficiency of RUNX1 causes FPD/AML in some
      families (deletions and frameshifts), mutant RUNX1 proteins (missense and
      nonsense) may also inhibit wild-type RUNX1, possibly creating a higher propensity
      to develop leukemia. This is consistent with the hypothesis that a second
      mutation has to occur, either in RUNX1 or another gene, to cause leukemia among
      individuals harboring RUNX1 FPD/AML mutations and that the propensity to acquire
      these additional mutations is determined, at least partially, by the initial
      RUNX1 mutation.

PMID- 11830490
TI  - Classical Hodgkin lymphoma is characterized by recurrent copy number gains of the
      short arm of chromosome 2.
AB  - Hodgkin- and Reed-Sternberg (HRS) cells microdissected from 41 classical Hodgkin
      lymphomas (cHL) of 40 patients comprising 8 lymphocyte-rich (cHL-LR), 16 nodular
      sclerosis (cHL-NS), 15 mixed-cellularity (cHL-MC), and 2 lymphocyte-depletion
      (cHL-LD) subtypes were analyzed by comparative genomic hybridization for
      recurrently imbalanced chromosomal subregions. Chromosomal gains most frequently
      involved chromosome 2p (54%), 12q (37%), 17p (27%), 9p and 16p (24% each), and
      17q and 20q (20% each), whereas losses primarily affected chromosome 13q (22%).
      Using fluorescence in situ hybridization, amplification of the REL oncogene was
      demonstrated within a distinct 2p15-p16 amplicon. The high frequency of 2p
      overrepresentations including REL, particularly in cHL-NS (88%), suggests that an
      alternative mechanism of constitutive activation of nuclear factor NF-kappaB is a
      hallmark of HRS cells. Hierarchical cluster analysis of chromosomal imbalances
      revealed a closer relationship among cHL-NS than other subtypes. Furthermore,
      there is a tendency for different subtypes of cHL-MC tumors characterized by
      different ages at the time of tumor onset and gain of chromosome 17p. The
      imbalance pattern of cHL subtypes suggests that different molecular pathways are
      activated, with REL or other genes on chromosomal band 2p15-p16 playing a
      fundamental role in the pathogenesis of classical Hodgkin lymphoma.

PMID- 11830489
TI  - Functional role of alternatively spliced deoxycytidine kinase in sensitivity to
      cytarabine of acute myeloid leukemic cells.
AB  - Development of resistance to cytarabine (AraC) is a major problem in the
      treatment of patients with acute myeloid leukemia (AML). Inactivation of
      deoxycytidine kinase (dCK) plays an important role in AraC resistance in vitro.
      We have identified inactive, alternatively spliced dCK forms in leukemic blasts
      from patients with resistant AML. Because these dCK-spliced variants were only
      detectable in resistant AML, it was hypothesized that they might play a role in
      AraC resistance in vivo. In the current study, the biologic role of the
      alternatively spliced dCK forms in AraC resistance was further investigated by
      retroviral transductions in rat leukemic cells. Introduction of inactive,
      alternatively spliced dCK forms into AraC-resistant K7 cells, with no endogenous
      wild-type (wt) dCK activity, could not restore AraC sensitivity, whereas wt dCK
      fully restored the AraC-sensitive phenotype. Transfection of alternatively
      spliced dCK forms into AraC-sensitive KA cells, as well as in human leukemic U937
      cells and in phytohemagglutinin-stimulated T cells, did not significantly change
      sensitivity toward AraC. In addition, cotransduction of wt dCK with alternatively
      spliced dCK in K7 cells did not result in altered sensitivity to AraC compared
      with K7 cells only transduced with wt dCK. These data indicate that the
      alternatively spliced dCK forms cannot act as a dominant-negative inhibitor on
      dCK wt activity when they are coexpressed in a single cell. However, a cell
      expressing alternatively spliced dCK forms that has lost wt dCK expression is
      resistant to the cytotoxic effects of AraC.

PMID- 11830491
TI  - Regulation of the Erk2-Elk1 signaling pathway and megakaryocytic differentiation
      of Bcr-Abl(+) K562 leukemic cells by Gab2.
AB  - In the blast crisis phase of chronic myelogenous leukemia (CML), Bcr-Abl(+)
      myeloblasts fail to undergo terminal maturation. The extracellular signal
      regulated kinase (Erk) mitogen-activated protein (MAP) kinase has been shown to
      mediate terminal differentiation of myeloid cells. Interestingly, Bcr-Abl(+) CML
      cell lines established from blast crisis were found to have low Erk MAP kinase
      activity. In this study, we analyzed the role of the Gab2 docking protein in
      regulation of the Erk MAP kinase in Bcr-Abl(+) K562 human CML cells.
      Overexpression of Gab2 in K562 cells resulted in transcriptional activation of
      the c-fos serum response element (SRE) promoter, whereas overexpression of SHP2,
      Grb2, and CrkL had no effect. Activation of the c-fos SRE transcriptional
      activity by Gab2 required tyrosine 604, which is a SHP2 docking site on Gab2, and
      the SHP2 tyrosine phosphatase activity. Elk1, c-Jun, and CHOP trans-reporting
      assays indicated that overexpression of Gab2 selectively activated the Erk2-Elk1
      signaling pathway. To determine cellular consequences of elevating the Gab2 level
      in K562 cells, stable cell lines for doxycycline-inducible expression of the wild
      type Gab2 (Gab2WT) and an SHP2-binding defective Gab2 (Gab2Tyr604Phe) were
      established. Analysis of these cell lines indicated that induction of Gab2WT
      expression, but not Gab2Tyr604Phe expression, led to Erk activation, growth
      arrest, cell spreading, and enlargement; expression of megakaryocyte/platelet
      lineage-specific integrins alphaIIb/beta3 (CD41/CD61); and upregulation of RNA
      for megakaryocyte/platelet proteins. All of these changes are characteristics of
      megakaryocytic differentiation. Together, these results reveal Gab2 as a limiting
      signaling component for Erk MAP kinase activation and terminal differentiation of
      K562 CML cells.

PMID- 11830492
TI  - BCL10 mutation does not represent an important pathogenic mechanism in gastric
      MALT-type lymphoma, and the presence of the API2-MLT fusion is associated with
      aberrant nuclear BCL10 expression.
AB  - Two recurrent translocations have been associated with mucosa-associated lymphoid
      tissue (MALT)-type lymphoma, t(11;18)(q21;q21) and t(1;14)(p22;q32). The first,
      t(11;18)(q21;q21), results in the fusion protein API2-MLT (API2-MALT1). Through
      t(1;14)(p22;q32), the BCL10 gene is entirely transferred to the IgH gene,
      resulting in its overexpression. Wild-type BCL10 is implicated in apoptosis, and
      it has been suggested that mutated forms gain oncogenic activity. The occurrence
      of genomic BCL10 mutations in 35 gastric MALT-type lymphomas with or without
      t(11;18)(q21;q21) (10 and 25 cases, respectively) was investigated. DNA extracted
      from either whole tissue sections or microdissected clusters of tumor cells was
      used. Five polymerase chain reactions amplifying the coding exons were performed
      and were followed by direct sequencing of the products. Twenty differences with
      the published BCL10 sequence, all single nucleotide substitutions, were detected
      in 16 cases. Of these, 12 represented known polymorphisms, either at codon 8,
      213, or 5. Of the remaining 8 substitutions, 2 were silent and 6 resulted in
      amino acid substitutions. Mutation analysis results were correlated with the
      BCL10 expression pattern. Aberrant nuclear BCL10 expression was detected in 14
      cases. No association could be demonstrated between the latter and the presence
      of BCL10 mutations. In contrast, all 10 cases carrying t(11;18)(q21;q21) showed
      nuclear expression, whereas this staining pattern was absent in 21 of 25 cases
      without t(11;18)(q21;q21). These results demonstrate that BCL10 mutations are
      rare in gastric MALT-type lymphoma and are not related to the aberrant nuclear
      expression of BCL10. In contrast, they indicate that the presence of the API2-MLT
      fusion protein is associated with aberrant nuclear BCL10 expression.

PMID- 11830493
TI  - Cell surface proteoglycan syndecan-1 mediates hepatocyte growth factor binding
      and promotes Met signaling in multiple myeloma.
AB  - Heparan sulfate proteoglycans (HSPGs) play a crucial role in growth regulation by
      assembling signaling complexes and presenting growth factors to their cognate
      receptors. Within the immune system, expression of the HSPG syndecan-1 (CD138) is
      characteristic of terminally differentiated B cells, ie, plasma cells, and their
      malignant counterpart, multiple myeloma (MM). This study explored the hypothesis
      that syndecan-1 might promote growth factor signaling and tumor growth in MM. For
      this purpose, the interaction was studied between syndecan-1 and hepatocyte
      growth factor (HGF), a putative paracrine and autocrine regulator of MM growth.
      The study demonstrates that syndecan-1 is capable of binding HGF and that this
      growth factor is indeed a potent stimulator of MM survival and proliferation.
      Importantly, the interaction of HGF with heparan sulfate moieties on syndecan-1
      strongly promotes HGF-mediated signaling, resulting in enhanced activation of
      Met, the receptor tyrosine kinase for HGF. Moreover, HGF binding to syndecan-1
      promotes activation of the phosphatidylinositol 3-kinase/protein kinase B and
      RAS/mitogen-activated protein kinase pathways, signaling routes that have been
      implicated in the regulation of cell survival and proliferation, respectively.
      These results identify syndecan-1 as a functional coreceptor for HGF that
      promotes HGF/Met signaling in MM cells, thus suggesting a novel function for
      syndecan-1 in MM tumorigenesis.

PMID- 11830495
TI  - CD40 activation induces p53-dependent vascular endothelial growth factor
      secretion in human multiple myeloma cells.
AB  - It was previously demonstrated that p53 status in human multiple myeloma (MM)
      cells regulates distinct cell cycle responses to CD40 activation. In this study,
      the production of vascular endothelial growth factor (VEGF) and migration in MM
      cells triggered by CD40 activation was examined, and the influence of p53 status
      in regulating this process was determined. Two human MM cell lines that express
      wild-type p53 at permissive (28 degrees C) and mutant p53 at restrictive (37
      degrees C) temperatures were used as a model system. CD40 activation induces a 4
      fold (RPMI 8226) and a 6-fold (SV) increase in VEGF transcripts, respectively,
      under restrictive, but not permissive, temperatures. VEGF expression is
      significantly induced after CD40 activation in patient MM cells expressing mutant
      p53. Increased VEGF transcripts result in increased protein and secretion levels,
      as evidenced by immunoblotting and enzyme-linked immunosorbent assay. In a double
      chamber transmigration assay, CD40 activation of MM cells induced a 3-fold (RPMI
      8226) and a 5-fold (SV) increase in migration under restrictive, but not
      permissive, conditions. A 2- to 8-fold induction in migration of patient MM cells
      expressing mutant p53 was similarly observed. Transduction of MM cells with a
      luciferase reporter under the control of a human VEGF promoter further indicated
      that CD40-induced VEGF expression was mediated through a transcriptional control
      mechanism. Finally, adenovirus-mediated wild-type p53 overexpression down
      regulated CD40-induced VEGF expression and transmigration in MM cells expressing
      mutant p53. These studies demonstrate that CD40 induces VEGF secretion and MM
      cell migration, suggesting a role for CD40 in regulating MM homing and
      angiogenesis.

PMID- 11830494
TI  - p14(ARF) nuclear overexpression in aggressive B-cell lymphomas is a sensor of
      malfunction of the common tumor suppressor pathways.
AB  - p14(ARF), the alternative product from the human INK4a/ARF locus, antagonizes
      Hdm2 and mediates p53 activation in response to oncogenic stimuli. An
      immunohistochemical study of p14(ARF) expression in 74 samples of aggressive B
      cell lymphomas was performed, demonstrating an array of different abnormalities.
      A distinct nucleolar expression pattern was detected in nontumoral tissue and a
      subset of lymphomas (50/74). In contrast, a group of cases (8/74) showed absence
      of p14(ARF) expression, dependent either on promoter hypermethylation or gene
      loss. Additionally, 16 out of 74 cases displayed an abnormal nuclear p14(ARF)
      overexpression not confined to the nucleoli, as confirmed by confocal microscopy,
      and that was associated with high levels of p53 and Hdm2. A genetic study of
      these cases failed to show any alteration in the p14(ARF) gene, but revealed the
      presence of p53 mutations in over 50% of these cases. An increased growth
      fraction and a more aggressive clinical course, with a shortened survival time,
      also characterized the group of tumors with p14(ARF) nuclear overexpression.
      Moreover, this p14(ARF) expression pattern was more frequent in tumors displaying
      accumulated alterations in the p53, p16(INK4a), and p27(KIP1) tumor supressors.
      These observations, together with the consideration of the central role of
      p14(ARF) in cell cycle control, suggest that p14(ARF) abnormal nuclear
      overexpression is a sensor of malfunction of the major cell cycle regulatory
      pathways, and consequently a marker of a high tumor aggressivity.

PMID- 11830496
TI  - Single-translocation and double-chimeric transcripts: detection of NUP98-HOXA9 in
      myeloid leukemias with HOXA11 or HOXA13 breaks of the chromosomal translocation
      t(7;11)(p15;p15).
AB  - It has been demonstrated that the chromosomal translocation t(7;11)(p15;p15) in
      patients with human acute myelogenous leukemia (AML) and chronic myelogenous
      leukemia (CML) invariably involves fusion of the nucleoporin gene, NUP98, on
      chromosome 11 and the class 1 HOX gene, HOXA9, on chromosome 7, and that the
      fusion gene NUP98-HOXA9 is an important gene in myeloid leukemogenesis. Here are
      reported 2 novel chromosome 7p15 targets of the t(7;11)(p15;p15) chromosomal
      translocation in 2 patients with CML and myelodysplastic syndrome (MDS). Southern
      blot and polymerase chain reaction (PCR) analyses of leukemia cell DNA failed to
      show rearrangement of HOXA9, whereas NUP98 was found to be rearranged in both
      cases. Reverse transcription-PCR analysis using a NUP98 primer and a degenerate
      primer corresponding to the third helix of the homeodomain of HOXA demonstrated
      that NUP98 was fused in-frame to HOXA11 in the patient with CML and to HOXA13 in
      the patient with MDS. The chromosomal breakpoints on 7p15 were located within
      introns of HOXA11 or HOXA13 genes. In both patients chimeric NUP98-HOXA9
      transcripts were also observed. These findings suggest that AbdB-type HOXA genes
      are common targets of t(7;11)(p15;p15) chromosomal translocations and that a
      single translocation can produce more than one NUP98-HOXA fusion gene, presumably
      because of altered splicing.

PMID- 11830497
TI  - Regulation of polymorphonuclear leukocyte degranulation and oxidant production by
      ceramide through inhibition of phospholipase D.
AB  - Exogenous C(2)-ceramide has been shown to inhibit polymorphonuclear leukocyte
      (PMN) phagocytosis through inhibition of phospholipase D (PLD) and downstream
      events, including activation of extracellular signal-regulated kinases 1 and 2,
      leading to the hyphothesis that the sphingomyelinase pathway is involved in
      termination of phagocytosis. Here it is postulated that increased PLD activity
      generating phosphatidic acid and diacylglycerol (DAG) is essential for superoxide
      release and degranulation and that ceramide, previously shown to be generated
      during PMN activation, inhibits PLD activation, thereby leading to inhibition of
      PMN function. When PMNs were primed with granulocyte colony-stimulating factor (G
      CSF) and then activated with N-formyl-methionyl-leucyl-phenylalanine (FMLP), C(2)
      ceramide (10 microM) completely inhibited release of superoxide, lactoferrin, and
      gelatinase; the DAG analog sn-1,2-didecanoylglycerol (DiC10) (10 microM) restored
      oxidase activation and degranulation in the ceramide-treated cells. Similarly,
      C(2)-ceramide inhibited oxidase activity and degranulation of PMNs treated with
      cytochalasin B followed by FMLP, and DiC10 restored function. In contrast, C(2)
      ceramide did not inhibit phosphorylation of p47phox or p38 mitogen-activated
      protein kinase, or translocation of p47phox, PLD-containing organelles, adenosine
      diphosphate-ribosylation factor 1, RhoA, protein kinase C (PKC)-beta or PKC-alpha
      to the plasma membrane in G-CSF or cytochalasin B-treated, FMLP-activated PMNs.
      PLD activity increased by 3-fold in G-CSF-primed PMNs stimulated by FMLP and by
      30-fold in cytochalasin B-treated PMNs stimulated by FMLP. Both PLD activities
      were completely inhibited by 10 microM C(2)-ceramide. In conclusion, superoxide,
      gelatinase, and lactoferrin release require activation of the PLD pathway in
      primed PMNs and cytochalasin B-treated PMNs. Ceramide may affect protein
      interactions with PLD in the plasma membrane, thereby attenuating PMN activation.

PMID- 11830498
TI  - Rapid establishment of dendritic cell chimerism in allogeneic hematopoietic cell
      transplant recipients.
AB  - Regeneration of hematopoiesis after allogeneic hematopoietic cell transplantation
      (HCT) involves conversion of the recipient's immune system to donor type. It is
      likely that distinct cell lineages in the recipient reconstitute at different
      rates. Dendritic cells (DCs) are a subset of hematopoietic cells that function as
      a critical component of antigen-specific immune responses because they modulate T
      cell activation, as well as induction of tolerance. Mature DCs are transferred
      with hematopoietic grafts and subsequently arise de novo. Little information
      exists about engraftment kinetics and turnover of this cell population in
      patients after allogeneic HCT. This study examined the kinetics of DC chimerism
      in patients who underwent matched sibling allogeneic HCT. T-cell, B-cell, and
      myelocytic and monocytic chimerism were also studied. Peripheral blood cells were
      analyzed at defined intervals after transplantation from 19 patients with various
      hematologic malignancies after treatment with myeloablative or nonmyeloablative
      preparatory regimens. Cell subsets were isolated before analysis of chimerism.
      Despite the heterogeneity of the patient population and preparatory regimens, all
      showed rapid and consistent development of DC chimerism. By day +14 after
      transplantation approximately 80% of DCs were of donor origin with steady
      increase to more than 95% by day +56. Earlier time points were examined in a
      subgroup of patients who had undergone nonmyeloablative conditioning and
      transplantation. These data suggest that a major proportion of blood DCs early
      after transplantation is donor-derived and that donor chimerism develops rapidly.
      This information has potential implications for manipulation of immune responses
      after allogeneic HCT.

PMID- 11830500
TI  - A broad T-cell repertoire diversity and an efficient thymic function indicate a
      favorable long-term immune reconstitution after cord blood stem cell
      transplantation.
AB  - Cord blood (CB) is used increasingly as a source of hematopoietic stem cells
      because of a lower risk of acute and chronic graft-versus-host disease (GVHD).
      However, there is some concern regarding the ability to adequately reconstitute
      host immune response due to the immaturity and naivety of CB T cells. This study
      was designed to evaluate T-cell reconstitution using combined approaches of
      phenotyping, analysis of alphabeta T-cell receptor (TCR) diversity, and
      assessment of ex vivo thymic function by measuring TCR rearrangement excision
      circles (TRECs). Ten patients who underwent CB transplantation for high-risk
      hematologic disorders were compared to a reference group of 19 age- and GVHD
      matched patients who underwent transplantation with non-T cell-depleted bone
      marrow from an HLA-identical sibling donor. TREC values correlated with the
      relative number of naive T cells and with TCR repertoire polyclonality. During
      the first year after transplantation, TCR repertoires were highly abnormal and
      TREC values low in both groups. Notably, 2 years after transplantation onward
      TREC values as well as TCR diversity were higher in CB recipients than in
      recipients of bone marrow transplants. These data indicate an efficient thymic
      regeneration pathway from CB lymphoid progenitors despite the low number of cells
      infused compared to bone marrow, arguing for a complete clinical immune recovery
      after CB transplantation.

PMID- 11830499
TI  - Unique patterns of surface receptors, cytokine secretion, and immune functions
      distinguish T cells in the bone marrow from those in the periphery: impact on
      allogeneic bone marrow transplantation.
AB  - The "conventional" NK1.1(-) T cells from mouse blood and marrow were compared
      with regard to surface receptors, cytokine secretion, and function. Most blood
      NK1.1(-) CD4(+) and CD8(+) T cells expressed the naive
      CD44(int/lo)CD62L(hi)CD45RB(hi) T-cell phenotype typical of those in the
      peripheral lymphoid tissues. In contrast, most marrow NK1.1(-) CD4(+) and CD8(+)
      T cells expressed an unusual CD44(hi)CD62L(hi)CD45RB(hi) phenotype. The blood
      NK1.1(-) CD4(+) T cells had a naive T-helper cytokine profile and a potent
      capacity to induce lethal graft versus host (GVH) disease in a C57BL/6 donor to a
      BALB/c host bone marrow transplantation model. In contrast, the marrow NK1.1(-)
      CD4(+) T cells had a Th0 cytokine profile and failed to induce lethal GVH
      disease, even at 20-fold higher numbers than those from the blood. NK1.1(-)
      CD8(+) T cells from the blood but not the marrow induced lethal GVH disease.
      Nevertheless, the marrow NK1.1(-) CD8(+) T cells induced potent antitumor
      activity that was augmented by marrow NK1.1(-) CD4(+) T cells and facilitated
      hematopoietic progenitor engraftment. The inability of marrow CD4(+) and CD8(+) T
      cells to induce GVH disease was associated with their inability to expand in the
      blood and gut of allogeneic recipients. Because neither the purified marrow
      CD4(+) or CD8(+) T cells induced GVH disease, their unique features are desirable
      for inclusion in allogeneic bone marrow or hematopoietic progenitor transplants.

PMID- 11830501
TI  - Blockade of B7/CD28 in mixed lymphocyte reaction cultures results in the
      generation of alternatively activated macrophages, which suppress T-cell
      responses.
AB  - Blockade of B7/CD28 costimulation allows human haploidentical bone marrow
      transplantation without graft-versus-host disease. This study shows that blockade
      of B7/CD28 in anergizing mixed lymphocyte reaction (MLR) cultures of peripheral
      blood mononuclear cells results in the generation of alternatively activated
      macrophages (AAMphi). In contrast, priming MLR cultures result in generation of
      classically activated macrophages (CAMphi). AAMphi had enhanced expression of
      CD14, major histocompatibility complex class II, and CD23; produced alternative
      macrophage activation-associated CC-chemokine 1 (AMAC-1) chemokine; and displayed
      increased phagocytotic activity but decreased ability for antigen presentation.
      Suppression subtractive hybridization revealed that although AAMphi had undergone
      terminal maturation and differentiation, they entered a distinct gene expression
      program as compared with CAMphi and selectively expressed beta2-microglobulin,
      lysozyme, ferritin heavy and light chain, and the scavenger receptors macrophage
      mannose receptor and sortilin. Anergic T cells isolated from cultures that led to
      the development of AAMphi produced low amounts of interleukin-2 (IL-2), IL-4, and
      interferon-gamma, but high amounts of IL-10. Addition of anti-IL-10 neutralizing
      monoclonal antibody in anergizing cultures reversed the functional
      characteristics of AAMphi, indicating that at least one mechanism involved in the
      generation of AAMphi was mediated by IL-10. Importantly, when added in MLR
      cultures, AAMphi suppressed T-cell responses. Therefore, besides direct
      inhibition of T-cell costimulation, blockade of B7/CD28 may facilitate induction
      of T-cell unresponsiveness by generating AAMphi. Because in healthy individuals,
      AAMphi are found in the placenta and lung, where they protect from unwanted
      immune reactivity, the results suggest that AAMphi may play a critical role in
      the induction of transplantation tolerance.

PMID- 11830502
TI  - Recurrent involvement of the REL and BCL11A loci in classical Hodgkin lymphoma.
AB  - Comparative genomic hybridization studies have shown gains in chromosome region
      2p as the most common imbalance in classical Hodgkin lymphoma (cHL). The minimal
      region of gain contained 2 candidate oncogenes, REL and BCL11A. This study
      examined the involvement of REL and BCL11A loci in 44 primary cases of cHL by
      combined immunophenotyping and interphase cytogenetics (FICTION). A median 2p13
      copy number above the tetraploid range was detected in 24 (55%) cases. Adjustment
      for centromere 2 copy number indicated gains of 2p13 in 11 of 31 cHLs (35%) with
      8 (26%) high-level amplifications. One cHL displayed selective amplification of
      the REL locus not affecting BCL11A; another case studied by FICTION and a cHL
      with cytogenetic 2p change investigated by fluorescence in situ hybridization
      showed signal patterns suggesting breakpoints in the region spanned by the REL
      probe. These data indicate that REL rather than BCL11A may be the target of the
      2p13 alterations in cHL.

PMID- 11830503
TI  - Overexpression of ornithine decarboxylase enhances endothelial proliferation by
      suppressing endostatin expression.
AB  - Angiogenesis, an essential process for tumor growth, is regulated by endothelial
      proliferation factors and their inhibitors such as endostatin. Endostatin, a
      carboxyl-terminal fragment of type XVIII collagen, inhibits endothelial
      proliferation, angiogenesis, and tumor growth. Ornithine decarboxylase (ODC), a
      molecule that is overexpressed in various cancers, is associated with promoting
      tumor growth and angiogenesis. We found that ODC-overexpressing human cancer
      cells and breast cancer specimens showed suppressed expression of type XVIII
      collagen and endostatin. We hypothesized that ODC overexpression may facilitate
      angiogenesis in tumors by suppressing endostatin expression. ODC-overexpressing
      COS cells, which showed suppressed type XVIII collagen and endostatin expression,
      were established. Conditioned media derived from these cells, containing
      decreased levels of endostatin, induced significant endothelial proliferation.
      ODC-overexpressing cells, when transplanted into nude mice, suppressed type XVIII
      collagen expression and promoted neovascularization in vivo. Thus, overexpression
      of ODC facilitates endothelial proliferation by suppressing endostatin
      expression.

PMID- 11830504
TI  - Long-term salvage therapy with cyclosporin A in refractory idiopathic
      thrombocytopenic purpura.
AB  - Treatment of severe, chronic idiopathic thrombocytopenic purpura (ITP) refractory
      to most usual therapies is a difficult challenge. Little information exists on
      the clinical use of cyclosporin A (CyA) in the treatment of ITP. This report
      describes long-term treatment with CyA (median, 40 months) and follow-up (median,
      36.8 months) in 12 adult patients with resistant ITP. CyA used in relatively low
      doses (2.5-3 mg/kg of body weight per day) led to a clinical improvement in 10
      patients (83.3%). Five had a complete response (41.1%), 4 a complete response to
      maintenance therapy (33.3%), and one a partial response (8.3%). Two patients had
      no response. Most patients with a response (60%) had a long-term remission (mean,
      28.6 months) after discontinuation of CyA. One patient had a relapse of ITP 4
      years after CyA therapy was stopped. Side effects were moderate and transient,
      even in patients dependent on continued CyA treatment. CyA seems to represent
      reasonable salvage treatment in severe, potentially life-threatening, refractory
      ITP.

PMID- 11830505
TI  - Unusual viral infections (progressive multifocal leukoencephalopathy and
      cytomegalovirus disease) after high-dose chemotherapy with autologous blood stem
      cell rescue and peritransplantation rituximab.
AB  - Efforts to reduce relapse of non-Hodgkin lymphoma after autologous
      transplantation have included ex vivo stem cell selection and/or
      peritransplantation immunotherapy. The late infectious and immunologic
      consequences of these maneuvers are not well understood, although an increase in
      early cytomegaloviral disease after CD34(+) stem cell selection and an alteration
      in immunoglobulin and T-cell recovery after peritransplantation rituximab has
      been noted. We report the first 2 cases of progressive multifocal
      leukoencephalopathy caused by JC papovavirus after autologous peripheral blood
      stem cell transplantation and a case each of cytomegalovirus retinitis and
      pneumonitis. All 4 patients experienced significant impairment of CD4 T-cell
      recovery, placing them at risk for these unusual viral infections. The clustering
      of cases is concerning because all occurred shortly after the introduction of
      peritransplantation rituximab into treatment protocols (4 of 62 immunotherapy
      recipients compared with 0 of 276 without; z = 3.595; P <.001), although a direct
      association with this CD20 B-cell-directed therapy remains speculative.

PMID- 11830506
TI  - Clinical utility of the reticulocyte hemoglobin content in the diagnosis of iron
      deficiency.
AB  - Determination of the reticulocyte hemoglobin content (CHr) provides an early
      measure of functional iron deficiency because reticulocytes are the earliest
      erythrocytes released into blood and circulate for only 1 to 2 days. The CHr in
      78 patients undergoing bone marrow examination was measured to assess its
      clinical utility for the diagnosis of iron deficiency. Twenty-eight patients were
      iron deficient, based on the lack of stainable iron in the aspirate. The
      diagnostic power of CHr is limited in patients with high mean cellular volume
      (MCV) or red cell disorders such as thalassemia. However, when patients with MCV
      more than 100 fL are excluded, receiver operator curve analysis of CHr, ferritin,
      transferrin saturation, and MCV demonstrates that CHr has the highest overall
      sensitivity and specificity of these peripheral blood tests for predicting the
      absence of bone marrow iron stores.

PMID- 11830507
TI  - Germline FAS gene mutation in a case of ALPS and NLP Hodgkin lymphoma.
AB  - FAS germline mutations have been associated with the development of autoimmune
      lymphoproliferative syndrome (ALPS). Occurrence of Hodgkin lymphoma (HL) has been
      reported in 2 families with ALPS. In both families an uncle of the index patient
      developed HL. A 15-year-old boy with autoimmune thrombopenia, lymphadenopathy,
      and splenomegaly for 6 years was studied. In an axillary lymph node biopsy
      nodular lymphocyte predominant (NLP) HL was diagnosed; in the areas between the
      nodules a proliferation of double-negative blastic T cells were present,
      suggestive of ALPS. Analysis for the presence of a FAS gene mutation using the
      denaturing gradient gel electrophoresis technique indicated a mutation in exon 9.
      Direct sequence analysis revealed a mutation causing a substitution of arginine
      with glutamine at codon 234. Because ALPS and NLP HL are both highly infrequent
      conditions, the occurrence in at least 3 families suggests a causative
      relationship between germline FAS gene mutations and NLP HL.

PMID- 11830508
TI  - Residual factor VII activity and different hemorrhagic phenotypes in CRM(+)
      factor VII deficiencies (Gly331Ser and Gly283Ser).
AB  - Two cross-reacting material-positive (CRM(+)) factor VII (FVII) mutations,
      associated with similar reductions in coagulant activity (2.5%) but with mild to
      asymptomatic (Gly331Ser, c184 [in chymotrypsin numbering]) or severe (Gly283Ser,
      c140) hemorrhagic phenotypes, were investigated. The affected glycines belong to
      structurally conserved regions in the c184 through c193 and c140s activation
      domain loops, respectively. The natural mutants 331Ser-FVII and 283Ser-FVII were
      expressed, and in addition 331Ala-FVII and 283Ala-FVII were expressed because 3
      functional serine-proteases bear alanine at these positions. The 331Ser-FVII,
      present in several asymptomatic subjects, showed detectable factor Xa generation
      activity in patient plasma (0.7% +/- 0.2%) and in reconstituted system with the
      recombinant molecules (2.7% +/- 1.1%). The reduced activity of recombinant 283Ala
      FVII (7.2% +/- 2.2%) indicates that the full function of FVII requires glycine at
      this position, and the undetectable activity of 283Ser-FVII suggests that the
      oxydrile group of Ser283 participates in causing severe CRM(+) deficiency.
      Furthermore, in a plasma system with limiting thromboplastin concentration,
      283Ser-FVII inhibited wild-type FVIIa activity in a dose-dependent manner.

PMID- 11830510
TI  - Prognostic significance of elevated cyclooxygenase-2 expression in breast cancer.
AB  - Cyclooxygenase-2 (Cox-2) expression can induce mammary tumorigenesis in
      transgenic mice, and selective Cox-2 inhibitors are both chemopreventive and
      chemotherapeutic in rat models of breast cancer. We analyzed the expression of
      Cox-2 protein by immunohistochemistry in tissue array specimens of 1576 invasive
      breast cancers. Moderate to strong (elevated) expression of Cox-2 protein was
      observed in 37.4% of the tumors, and it was associated with unfavorable distant
      disease-free survival (P < 0.0001). Elevated Cox-2 expression was associated with
      a large tumor size, a high histological grade, a negative hormone receptor
      status, a high proliferation rate (identified by Ki-67), high p53 expression, and
      the presence of HER-2 oncogene amplification (P < 0.0001 for all comparisons),
      along with axillary node metastases and a ductal type of histology (P = 0.0001
      and P = 0.0017, respectively). Interestingly, association with the unfavorable
      outcome was especially apparent in the subgroups defined by estrogen receptor
      positivity, low p53 expression, and no HER-2 amplification (P < 0.0001 for all
      comparisons). These results indicate that elevated Cox-2 expression is more
      common in breast cancers with poor prognostic characteristics and is associated
      with an unfavorable outcome. The present findings support efforts to initiate
      clinical trials on the efficacy of Cox-2 inhibitors in adjuvant treatment of
      breast cancer.

PMID- 11830509
TI  - Cyclooxygenase-2 inhibition by celecoxib reduces proliferation and induces
      apoptosis in angiogenic endothelial cells in vivo.
AB  - Cyclooxygenase-2 (COX-2) is expressed within neovascular structures that support
      many human cancers. Inhibition of COX-2 by celecoxib delays tumor growth and
      metastasis in xenograft tumor models as well as suppresses basic fibroblast
      growth factor 2 (FGF-2)-induced neovascularization of the rodent cornea. The
      present studies were undertaken to evaluate possible mechanisms of the
      antiangiogenic and anticancer effects of celecoxib. Prostaglandin E(2) (PGE(2))
      and thromboxane B(2) (TXB(2)) were increased in rat corneas implanted with slow
      release pellets containing FGF-2 (338.6 ng of PGE(2)/g and 17.53 ng of TXB(2)/g)
      compared with normal rat corneas (63.1 ng of PGE(2)/g and 2.0 ng of TXB(2)/g).
      Celecoxib at 30 mg/kg/day p.o. inhibited angiogenesis (78.6%) and prostaglandin
      production by 78% for PGE(2) (72.65 ng/g) and 68% for TXB(2) (5.55 ng/g).
      Decreased prostaglandin production in corneas was associated with a 2.5-fold
      cellular increase in apoptosis and a 65% decrease in proliferation. Similar
      reductions in proliferation were observed in neovascular stroma (65-70%) of
      celecoxib-treated (dietary 160 ppm/day) xenograft tumors as well as in tumor
      cells (50-75%). Apoptosis was also increased in the tumor cells (2.2-3.0-fold) in
      response to celecoxib. Thus, the antitumor activity of celecoxib may be
      attributable, at least in part, to a direct effect on host stromal elements, such
      as the angiogenic vasculature.

PMID- 11830511
TI  - Possible oncogenic potential of DeltaNp73: a newly identified isoform of human
      p73.
AB  - p73, a recently identified gene highly homologous to p53, can transactivate p53
      target genes and induce apoptosis. Here we report the identification of an NH(2)
      terminal truncated isoform of human p73, DeltaNp73, which is capable of
      suppressing p53- and p73-dependent transactivation. We speculate that this
      suppression is achieved by competing for the DNA binding site in the case of p53
      and by direct association in the case of TAp73. Expression of DeltaNp73 in cancer
      cell lines also inhibited suppressive activity of p53 and TAp73 in colony
      formation, implying possible involvement of DeltaNp73 in oncogenesis by
      inhibiting the tumor-suppressive function of p53 and TAp73. Also reported is the
      identification of TAp73eta, a new member of the COOH-terminal truncated isoform
      of p73 and tissue-specific expression of these isoforms, along with other
      previously identified p73 isoforms.

PMID- 11830512
TI  - Role of the phosphatidylinositol 3'-kinase/PTEN/Akt kinase pathway in the
      overexpression of fatty acid synthase in LNCaP prostate cancer cells.
AB  - One of the most common molecular changes in cancer cells is the overexpression of
      fatty acid synthase (FAS), a key metabolic enzyme catalyzing the terminal steps
      in the synthesis of long chain saturated fatty acids. As part of our efforts to
      elucidate the mechanisms responsible for FAS overexpression, we have addressed
      the question whether overexpression of FAS may be linked to the frequently
      observed inactivation of PTEN and subsequent activation of the
      phosphatidylinositol 3'-kinase (PI3k) pathway. Using LNCaP prostate cancer cells
      as an experimental paradigm of FAS-overexpressing PTEN-null cancer cells, we
      demonstrate that LY294002, an inhibitor of the PI3k pathway causes a dramatic
      decrease in FAS protein expression. Smaller but still substantial effects are
      seen at the FAS mRNA level and at the level of transcriptional activity of FAS
      promoter-reporter constructs. Consistent with these findings, reintroduction of
      PTEN results in decreased levels of FAS expression in a manner that is dependent
      on its lipid phosphatase activity. In support of a role for Akt/protein kinase B
      as a downstream effector, cotransfection of constitutively active Akt1/protein
      kinase B alpha abrogates the inhibitory effects of PTEN expression and restores
      FAS promoter activity. Taken together, these results demonstrate that
      inactivation of PTEN and subsequent activation of the PI3k/Akt kinase pathway may
      play an important role in the overexpression of the FAS protein in cancer cells.

PMID- 11830513
TI  - High mobility group protein I(Y): a candidate architectural protein for
      chromosomal rearrangements in prostate cancer cells.
AB  - The extent of chromosomal rearrangements correlates positively with the level of
      expression of the nuclear matrix high mobility group (HMG) proteins HMGI(Y) when
      tested in three human prostate cancer cell lines (PC-3 > DU-145 > LNCaP).
      HMGI(Y), topoisomerase II, and A-T-rich sequences have been reported to be
      located at the base of the DNA loop domains in both the nucleus and chromosome
      and are juxtapositioned for chromosomal rearrangement. Transfecting and
      expressing full-length HMG-I into the LNCaP cell markedly enhanced the presence
      and heterogeneity of unbalanced (nonreciprocal) chromosomal rearrangements but
      not of balanced rearrangements. Unbalanced chromosomal rearrangements are common
      in solid human tumors.

PMID- 11830514
TI  - Green tea polyphenol epigallocatechin-3 gallate inhibits Her-2/neu signaling,
      proliferation, and transformed phenotype of breast cancer cells.
AB  - Overexpression of the epidermal growth factor receptor family member Her-2/neu in
      breast cancer is associated with poor prognosis. With evidence accumulating for a
      chemopreventive role of green tea polyphenols, the effects of epigallocatechin-3
      gallate (EGCG) on Her-2/neu-overexpressing breast cancer cells were examined.
      EGCG inhibited mouse mammary tumor virus (MMTV)-Her-2/neu NF639 cell growth in
      culture and soft agar. EGCG reduced signaling via the phosphatidylinositol 3-
      kinase, Akt kinase to NF-kappaB pathway because of inhibition of basal Her-2/neu
      receptor tyrosine phosphorylation. EGCG similarly inhibited basal receptor
      phosphorylation in SMF and Ba/F3 2 + 4 cells, which suggests the potential
      beneficial use of EGCG in adjuvant therapy of tumors with Her-2/neu
      overexpression.

PMID- 11830515
TI  - 3-Methyladenine DNA glycosylase-deficient Aag null mice display unexpected bone
      marrow alkylation resistance.
AB  - Most cells deficient in 3-methyladenine (3MeA) DNA glycosylase become sensitive
      to the lethal and clastogenic effects of alkylating agents. Surprisingly, myeloid
      progenitor bone marrow (BM) cells derived from Aag -/- mice were more resistant
      than those from wild-type mice to the cytotoxic effects of several alkylating
      agents. Moreover, an alkylation-resistant phenotype was observed in vivo using
      the BM micronucleus assay as a measure of chromosome damage. Flow cytometry
      indicated that in vivo alkylation resistance in Aag null BM cells may be
      restricted to cells of the myeloid lineage. These results show that in particular
      cell types, the initiation of base excision repair is more lethal to the cell
      than leaving the damaged bases unrepaired by Aag.

PMID- 11830516
TI  - Pulmonary and lymph node metastasis is associated with primary tumor interstitial
      fluid pressure in human melanoma xenografts.
AB  - Interstitial fluid pressure (IFP) is elevated in many experimental and human
      tumors, and high IFP is associated with poor prognosis in human cancer. The
      significance of elevated IFP in the development of metastatic disease was
      investigated in the present work by using A-07 human melanoma xenografts as
      models of cancer in humans. IFP was measured with the micropipette technique
      (tumor periphery) and the wick-in-needle technique (tumor center). Tumor hypoxia
      was studied by immunohistochemistry using pimonidazole as a hypoxia marker and by
      using a radiobiological assay. High central tumor IFP was found to be associated
      with the development of pulmonary (P = 0.000085) and lymph node (P = 0.000036)
      metastases in small (150-200 mm(3)) A-07 tumors. Hypoxic cells could not be
      detected in these tumors. Our study suggests that interstitial hypertension may
      facilitate tumor cell intravasation and, hence, promote metastasis by mechanisms
      independent of tumor hypoxia.

PMID- 11830517
TI  - Transendothelial function of human metastatic melanoma cells: role of the
      microenvironment in cell-fate determination.
AB  - On the basis of the ability of aggressive melanoma cells to participate in
      vasculogenic mimicry, particularly their expression of endothelial-associated
      genes, we examined the plasticity of human metastatic cutaneous melanoma cells
      with respect to vascular function. Fluorescently labeled metastatic melanoma
      cells were challenged to an ischemic microenvironment surgically induced in the
      hind limbs of nude mice. The data reveal the capability of these melanoma cells
      to express cell-fate determination molecules, normally expressed during embryonic
      vasculogenesis, and to participate in the neovascularization of circulation
      deficient muscle. These results demonstrate the powerful influence of the
      microenvironment on the transendothelial differentiation of aggressive melanoma
      cells, and may provide new perspectives on tumor cell plasticity that could be
      exploited for novel therapeutic strategies.

PMID- 11830518
TI  - Essential role of neural Wiskott-Aldrich syndrome protein in podosome formation
      and degradation of extracellular matrix in src-transformed fibroblasts.
AB  - Transformation of cells by the src oncogene causes dramatic changes in adhesive
      structures. In v-src-transformed 3Y1 rat fibroblasts (3Y1-src), there are actin
      rich protrusive structures called podosomes by which attachment to the
      extracellular matrix is thought to occur. In this study, we found that neural
      Wiskott-Aldrich syndrome protein (N-WASP) colocalizes with filamentous actin (F
      actin) in podosomes. Expression of dominant-negative mutants of N-WASP, Deltacof
      N-WASP and DeltaVPH N-WASP, both of which are incapable of activating the Arp2/3
      complex, suppressed podosome formation, suggesting that N-WASP is essential in
      this process. Localization of N-WASP in podosomes appears to be attributable to
      interaction between N-WASP and the SH3 domain of cortactin. Indeed,
      microinjection of the cortactin SH3 domain suppressed podosome formation. We also
      observed that 3Y1-src cells cultured on fibronectin degrade the fibronectin
      primarily at the podosomes and that the inhibition of podosome formation by
      Deltacof N-WASP abolishes the fibronectin degradation. These results suggest the
      importance of N-WASP in podosome formation and extracellular matrix degradation,
      which are processes thought to underlie the invasive phenotype of 3Y1-src cells.

PMID- 11830519
TI  - Activation of membrane-type matrix metalloproteinase 3 zymogen by the proprotein
      convertase furin in the trans-Golgi network.
AB  - Matrix metalloproteinases (MMPs), a family of zinc-dependent endopeptidases
      implicated in tumor invasion and metastasis, must undergo zymogen activation
      prior to expressing any proteolytic activity. Although the cysteine-switch model
      predicts the well-established autoactivation process, approximately 40% of the
      known MMPs possess a conserved RXKR motif between their pro- and catalytic
      domains and, thus, could be activated directly by members of the proprotein
      convertase family. To further understand this process, we analyzed the activation
      of proMT3-MMP as a model system. We demonstrated that the conversion of MT3-MMP
      zymogen into active form is dependent on both the furin-type convertase activity
      and the R(116)RKR motif. Consistently, MT3-MMP was colocalized with furin in the
      trans-Golgi network by confocal microscopy. However, neither furin activity nor
      its recognition site in MT3-MMP is required for the observed colocalization. In
      fact, the colocalization pattern remains intact, even in the presence of
      brefeldin A, an agent known to block endoplasmic reticulum to Golgi trafficking.
      Yet, brefeldin A completely blocked the activation of MT3-MMP. A23187, a calcium
      ionophore known to block furin maturation, also blocked proMT3-MMP activation but
      had minimal effect on the colocalization between MT3-MMP and furin. Thus, furin
      processes MT3-MMP zymogen in the trans-Golgi network, where they colocalize
      independently of their apparent enzyme-substrate relationship.

PMID- 11830520
TI  - NAD(P)H and collagen as in vivo quantitative fluorescent biomarkers of epithelial
      precancerous changes.
AB  - During the development of neoplasia, epithelial tissues undergo biochemical and
      structural changes that can manifest in tissue fluorescence. There have been
      several reports on different in vivo fluorescence characteristics between normal
      and precancerous (dysplastic) tissues. However, it has been difficult to identify
      and quantify the origins of these changes, mainly because of distortions
      introduced in measured tissue fluorescence spectra by tissue scattering and
      absorption. Such distortions can be removed by combining information in
      simultaneously measured fluorescence and reflectance spectra. Thus, we can
      recover the intrinsic (undistorted) tissue fluorescence. In this report, we show
      that extraction of the intrinsic fluorescence allows us: (a) to determine the
      fluorescence spectra of NAD(P)H and collagen in an in vivo environment, and (b)
      to use these NAD(P)H and collagen spectra to describe, quantitatively,
      diagnostically significant biochemical changes between normal and dysplastic
      tissues. Specifically, by analyzing intrinsic fluorescence of human epithelial
      tissue as it becomes deoxygenated in vivo, we can resolve the fluorescence
      spectra of NAD(P)H and collagen, two of the major tissue fluorophores. This is
      important because fluorescence depends on the local environment of the
      chromophore. Then, we extract the intrinsic fluorescence spectra of sites from 35
      patients with suspected cervical lesions and 7 patients with Barrett's esophagus
      and describe them accurately as a linear combination of NAD(P)H and collagen
      contributions. In both tissue cases, we find that low collagen and high NAD(P)H
      fluorescence characterizes the high-grade dysplastic lesions when compared with
      nondysplastic tissues. These data present evidence for the presence of detectable
      levels of NAD(P)H fluorescence in human epithelial tissues in an in vivo setting
      and demonstrate that NAD(P)H and collagen may be used as quantitative
      fluorescence biomarkers for in vivo detection of dysplasia in the cervix and the
      esophagus.

PMID- 11830521
TI  - Metabolic changes detected by in vivo magnetic resonance studies of HEPA-1 wild
      type tumors and tumors deficient in hypoxia-inducible factor-1beta (HIF-1beta):
      evidence of an anabolic role for the HIF-1 pathway.
AB  - Hypoxia-inducible factor-1 (HIF-1) regulates many pathways potentially important
      for tumor growth, including angiogenesis and glycolysis. Most attention has
      focused on its role in the response to hypoxia, but HIF-1 is also constitutively
      expressed in many tumors. To analyze the role of this pathway in vivo, we used
      magnetic resonance (MR) methods and complementary techniques to monitor metabolic
      changes in tumors derived from HEPA-1 mouse hepatoma lines that were either wild
      type (WT) or deficient in hypoxia-inducible transcription factor HIF-1beta (c4).
      The c4 tumors grew significantly more slowly than the WT tumors (P < 0.05), but
      were examined at a similar size (0.4-0.6 g). At the tumor size used in these
      studies, no differences in vascularity were observed, and MR parameters measured
      that related to tumor blood flow, vascularity, and oxygenation demonstrated no
      significant differences between the two tumor types. Unexpectedly, the ATP
      content of the c4 tumor was approximately 5 times less than in the WT tumor
      [measured in tumor extracts (P < 0.001) and by metabolic imaging (P < 0.05)].
      Noninvasive (31)P MR spectroscopy showed that the nucleoside triphosphate/P(i)
      ratio of the two tumor types was similar, so the low ATP content of the c4 tumors
      was not caused by (or a cause of) impaired cellular bioenergetics. Rather,
      glycine, an essential precursor for de novo purine formation, was significantly
      lower in the c4 tumors (P < 0.05), suggesting that ATP synthesis was impaired in
      the mutant tumor cells. Supporting evidence for this hypothesis came from the
      significantly lower concentrations of betaine, phosphocholine, and choline in the
      c4 tumors (P < 0.05); these are intermediates in an alternative pathway for
      glycine synthesis. No significant differences were seen in lactate or glucose
      content. MR resonances from phosphodiesters, which relate to the metabolic
      turnover of phospholipid membranes, were significantly lower in the WT tumors
      than in the c4 tumors, both in vivo (P < 0.05) and in extracts (P < 0.01). We
      propose that loss of up-regulation of expression of the genes for glucose
      transporters and glycolytic enzymes in the c4 tumors decreased formation of
      glycine, an essential precursor of ATP synthesis, and thus caused the low ATP
      content of the c4 tumors. In summary, these data suggest that disruption of the
      HIF-1 pathway in these tumor cells impairs the supply of anabolic precursors
      required for cell synthesis. They suggest potential biochemical targets that may
      be modified by therapy blocking HIF-1 function.

PMID- 11830522
TI  - Germ-line p53-targeted disruption inhibits helicobacter-induced premalignant
      lesions and invasive gastric carcinoma through down-regulation of Th1
      proinflammatory responses.
AB  - p53 is a tumor suppressor gene that is mutated in many human malignancies,
      including gastric cancer. It remains unclear why patients with germ-line p53
      mutations (i.e., Li-Fraumeni syndrome) are not at increased risk for gastric
      adenocarcinoma, despite the fact that they show a high rate of many other tumors.
      Furthermore, the precise relationship between germ-line p53 mutations and the
      response to chronic bacterial infections (such as Helicobacter spp.) has not been
      investigated. To assess the role of germ-line p53 deletions in modulating the
      progression to gastric cancer, p53(+/-) and wild-type (WT) C57BL/6 mice were
      infected with H. felis. The gastric pathology and immune response in these two
      groups of mice were analyzed for up to 15 months postinfection. The gastric
      fundus and antrum were evaluated independently using a 0-4 scale to score
      inflammation, parietal and chief cell loss, mucus metaplasia, and helicobacter
      colonization. Nonparametric statistical analysis was performed to determine the
      effects of p53(+/-), infection status, and postinoculation (p.i.) time on
      inflammation, preneoplastic changes, invasive lesions, and helicobacter
      colonization. mRNA expression for gammaIFN, interleukin (IL)-1, IL-10, and IL-4
      was quantified by PCR. Sera were also evaluated for H. felis antibody by ELISA.
      Antral inflammation increased significantly with time in infected mice. There was
      a significant, protective effect on the development of preneoplastic fundic
      lesions and invasive carcinoma attributable to the deletion of one p53 allele (P
      < 0.05). Submucosal invasive foci were observed in 9 of 11 WT-infected mice
      ranging from 13 to 15 months p.i.; invasion of adjacent submucosal blood vessels
      by glandular epithelia also was present in 5 of these mice. None of these lesions
      were observed in 33 p53(+/-) mice, infected or not, at any time p.i. p53(+/-)
      mice had significantly higher helicobacter colonization consistent with a Th2
      host response. In sera from WT mice, IgG2a, considered a proinflammatory Th1
      response, continued to rise throughout the 15-month study (P < 0.004). In
      contrast, IgG2a levels of the p53(+/-) mice were 50-60% lower than those of the
      WT mice at each time point (P range, <0.012 to 0.002) and did not progress in
      magnitude between 12 and 15 months of chronic H. felis infection (P = 0.167).
      mRNA levels for gammaIFN and IL-1 were significantly up-regulated in WT mice
      infected with H. felis (P < 0.05) but were slightly elevated or were at
      background levels in p53(+/-) mice. IL-10 and IL-4 mRNA expression was not
      significantly different from control samples. Our results support the hypothesis
      that germ-line deletion of one p53 allele results in a down-regulated Th1
      response to gastric helicobacter infection, possibly because of T-cell
      senescence, which may indirectly protect against the development of gastric
      cancer and other epithelial-derived neoplasms associated with chronic
      inflammation.

PMID- 11830523
TI  - Molecular cloning and functional analysis of a novel cadmium-responsive proto
      oncogene.
AB  - The molecular mechanisms potentially responsible for cell transformation and
      tumorigenesis induced by cadmium, a human carcinogen, were investigated by
      differential gene expression analysis of BALB/c-3T3 cells transformed with
      cadmium chloride (CdCl(2)). Differential display analysis of gene expression
      revealed consistent overexpression of mouse translation initiation factor 3
      (TIF3; GenBank accession number AF271072) in the cells transformed with CdCl(2)
      when compared with nontransformed cells. The predicted protein encoded by TIF3
      cDNA exhibited 99% similarity to human eukaryotic initiation factor 3 p36
      protein. A M(r) 36,000 protein was detected in cells transfected with an
      expression vector containing TIF3 cDNA. Transfection of NIH3T3 cells with an
      expression vector containing TIF3 cDNA resulted in overexpression of the encoded
      protein, and this was associated with cell transformation, as evidenced by the
      appearance of transformed foci exhibiting anchorage-independent growth on soft
      agar and tumorigenic potential in nude mice. Expression of the antisense RNA
      against TIF3 mRNA resulted in significant reversal of oncogenic potential of the
      CdCl(2)-transformed BALB/c-3T3 cells. Taken together, these findings demonstrate
      for the first time that the cell transformation and tumorigenesis induced by
      CdCl(2) are due, at least in part, to the overexpression of TIF3, a novel cadmium
      responsive proto-oncogene.

PMID- 11830524
TI  - Identification of molecular targets associated with selenium-induced growth
      inhibition in human breast cells using cDNA microarrays.
AB  - Past research indicated that methylseleninic acid (MSA) is an excellent tool for
      investigating the cancer chemopreventive action of selenium in vitro. The present
      study was designed to examine the cellular and molecular effects of MSA in the
      MCF10AT1 and MCF10AT3B premalignant human breast cells. After exposure to MSA,
      both cell lines exhibited a dose- and time-dependent growth-inhibitory response
      as determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
      (MTT) cell proliferation assay. Further characterization of cellular and
      molecular changes was carried out only with the MCF10AT1 cells. Flow cytometry
      analysis showed that MSA blocked cell cycle progression at the G(0)-G(1) phase.
      Induction of apoptosis was also observed with the use of either the terminal
      deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) or the
      annexin V binding method. cDNA microarray analyses with cell cycle- and apoptosis
      targeted arrays were then applied to profile the gene expression changes
      mediating these two cellular events. The analyses were conducted at 6 and 12 h of
      MSA treatment using synchronized cells. The expression signals of 30 genes were
      found to be significantly altered by MSA. These genes fall into three categories:
      cell cycle checkpoint controllers (e.g., cyclins, cdcs, cdks, E2F family
      proteins, and serine/threonine kinases), apoptosis regulatory genes (e.g., Apo-3,
      c-jun, and cdk5/cyclin D1), and signaling molecules [e.g., mitogen-activated
      protein (MAP)/extracellular signal-regulated protein kinase (ERK) and
      phosphatidylinositol 3'-kinase (PI3k) cascade genes]. The expression changes of
      15 genes were selected for verification by Western or semiquantitative reverse
      transcription-PCR analyses. An agreement rate of 60% (9 of 15) was obtained from
      these confirmation experiments. On the basis of the above findings, tentative
      signaling pathways mediating the outcome of selenium-induced cell cycle arrest
      and apoptosis are proposed. The present study thus demonstrated the feasibility
      of applying cDNA microarray technology in delineating the mechanisms of the
      action of selenium and in pinpointing molecular targets as potential biomarkers
      for evaluating the efficacy of selenium intervention.

PMID- 11830525
TI  - Biological and prognostic significance of interphase fluorescence in situ
      hybridization detection of chromosome 13 abnormalities (delta13) in multiple
      myeloma: an eastern cooperative oncology group study.
AB  - Chromosome 13 abnormalities (Delta13) have been associated with an unfavorable
      prognosis in patients with multiple myeloma (MM). The significance of this has
      been unresolved because of diverse methods of detection and heterogeneous groups
      of patients. We conducted a study of Delta13 in patients entered into the Eastern
      Cooperative Oncology Group trial E9486/E9487. Patients with newly diagnosed MM
      (median follow-up of survivors >100 months) were studied for Delta13, using bone
      marrow samples obtained at study enrollment. We used interphase fluorescence in
      situ hybridization with the probes LSI13 (Rb)/D13S319 with simultaneous
      immunofluorescence detection of bone marrow plasma cells (PCs). We detected
      Delta13 in 176 of 325 (54%) evaluable patients. Patients with Delta13 were more
      likely to have a serum monoclonal protein at a concentration < or =1 g/dl (22
      versus 13%; P = 0.04), light-chain-only MM (19.3 versus 10.8%; P = 0.04), gamma
      light chain (42 versus 28%; P = 0.027), stage III (56 versus 42%; P = 0.014), and
      be female (60 versus 50%; P = 0.087). The PC labeling index and Delta13
      correlated (P = 0.03). Patients with Delta13 were less likely to respond to
      treatment (74 versus 63%; P = 0.041) and had a significantly shorter median
      overall survival (34.9 versus 51 months; P = 0.021). The association of Delta13
      and survival remained an independent prognostic variable in a regression model.
      Among patients with Delta13, those receiving IFN had a worse overall survival
      that those not receiving the medication (P = 0.03). The presence of Delta13 is an
      important and independent adverse prognostic factor in newly diagnosed MM and is
      associated with specific biological features.

PMID- 11830526
TI  - AIbZIP, a novel bZIP gene located on chromosome 1q21.3 that is highly expressed
      in prostate tumors and of which the expression is up-regulated by androgens in
      LNCaP human prostate cancer cells.
AB  - Androgens play an important role in the development and physiology of the normal
      prostate as well as in prostate cancer cell proliferation. Comparison of the mRNA
      expression profiles of control and R1881-treated cultures of LNCaP human prostate
      cancer cells using cDNA subtraction led to the identification of a novel
      transcription factor that we named Androgen-Induced bZIP (AIbZIP) protein. AIbZIP
      is a 395 aa protein with homology to cyclic AMP-responsive element binding
      protein/activating transcription factor transcription factors. It contains an
      NH(2)-terminal activation domain, a central bZIP domain, and a COOH-terminal
      transmembrane domain. The AIbZIP gene is localized on chromosome 1q21.3 and
      consists of 10 exons. A major 1.7-kb transcript was detected exclusively in the
      prostate as well as in breast and prostate cancer cell lines. Androgens up
      regulate AIbZIP mRNA and protein levels in a dose-dependent manner. The kinetics
      of AIbZIP mRNA up-regulation and the results of experiments with cycloheximide
      suggest that AIbZIP may be a delayed response gene. Immunoreactive AIbZIP protein
      was primarily detected in the cytoplasm of prostatic luminal epithelial cells.
      Similarly, full-length AIbZIP-green fluorescent protein fusion proteins were
      localized in the cytoplasm of LNCaP cells, whereas a truncated form of AIbZIP
      lacking the putative transmembrane domain was exclusively nuclear. Examination of
      AIbZIP protein and mRNA expression in a series of transurethral resection of the
      prostate and needle biopsy specimens indicated that AIbZIP is expressed at higher
      levels in cancerous prostate cells compared with noncancerous prostate cells. The
      highly tissue-specific expression profile, androgen regulation, chromosomal
      localization, and expression profile of AIbZIP in prostate tumors suggest that
      AIbZIP may play an important role in prostate cancer and in androgen receptor
      signaling in prostate cells. Future studies will confirm a possible relationship
      between AIbZIP and prostate cancer.

PMID- 11830527
TI  - Manipulation of pulmonary prostacyclin synthase expression prevents murine lung
      cancer.
AB  - Inhibition of cyclooxygenase (COX) activity decreases eicosanoid production and
      prevents lung cancer in animal models. Prostaglandin (PG) I(2) (PGI(2),
      prostacyclin) is a PGH(2) metabolite with anti-inflammatory, antiproliferative,
      and antimetastatic properties. The instability of PGI(2) has limited its
      evaluation in animal models of cancer. We hypothesized that pulmonary
      overexpression of prostacyclin synthase may prevent the development of murine
      lung tumors. Transgenic mice with selective pulmonary prostacyclin synthase
      overexpression were exposed to two distinct carcinogenesis protocols: an
      initiation/promotion model and a simple carcinogen model. The transgenic mice
      exhibited significantly reduced lung tumor multiplicity (tumor number) in
      proportion to transgene expression, a dose-response effect. Moreover, the highest
      expressing mice demonstrated reduced tumor incidence. To investigate the
      mechanism for protection, we evaluated PG levels and inflammatory responses. At
      the time of sacrifice following one carcinogenesis model, the transgenics
      exhibited only an increase in 6-keto-PGF(1alpha), not a decrease in PGE(2). Thus,
      elevated PGI(2) levels and not decreased PGE(2) levels appear to be necessary for
      the chemopreventive effects. When exposed to a single dose of butylated
      hydroxytoluene, transgenic mice exhibited a survival advantage; however,
      reduction in alveolar inflammatory response was not observed. These studies
      demonstrate that manipulation of PG metabolism downstream from COX produces even
      more profound lung cancer reduction than COX inhibition alone and could be the
      basis for new approaches to understanding the pathogenesis and prevention of lung
      cancer.

PMID- 11830528
TI  - 1alpha,25-(OH)(2)-D(3) and its synthetic analogue decrease tumor load in the
      Apc(min) Mouse.
AB  - Both calcium and vitamin D are thought to be able to inhibit colon
      carcinogenesis. To better define the effects of vitamin D, we studied 1alpha,25
      (OH)(2)-D(3) and a noncalcemic synthetic analogue of vitamin D(3) (VD(3)) in the
      Apc(min) mouse. Female Apc(min) mice 4-5 weeks old were randomized to four
      groups: a VD(3)-treated group (n = 11) were given injections of 0.01 microg of
      1alpha,25-(OH)(2)-D(3) i.p. three times per week; an analogue-treated group (n =
      10) received 5 microg of 1alpha,25-(OH)(2)-16-ene-19-nor-24-oxo-D(3) i.p. three
      times per week; and a control group (n = 12) received sham injections of PBS. A
      sulindac-treated group (n = 10) was used as a positive control. Doses of these
      compounds were chosen based on previous toxicity studies in mice and rats. After
      10 weeks of treatment, mice were killed and two observers (S. H., R. W. I.),
      blinded to treatment, scored polyp number and size. Tumor number was not affected
      with 1alpha,25-(OH)(2)-D(3) or vitamin D analogue administration. A significant
      decrease in total tumor load (sum of all polyp areas) over the entire
      gastrointestinal tract was seen in the analogue (36% decrease; P < 0.05) and the
      VD(3) groups (46%; P < 0.001). There was a significant decrease in polyp number
      (49%; P < 0.001) and polyp area (70%; P < 0.001) in the sulindac group. Reverse
      transcription-PCR of the total RNA derived from intestinal tissue revealed
      expression of the vitamin D receptor throughout the small intestine and the
      colon. Serum calcium levels in the analogue group were not elevated at week 4 of
      treatment and only moderately elevated (22%) by week 8 (P < or =0.001). In
      contrast, serum calcium in the VD(3) group was significantly elevated (P < or
      =0.001) at weeks 4 (23%) and 8 (45%). Food intake and growth rate were
      significantly lower in the VD(3) group (26%, P < 0.001, and 27%, P < 0.001,
      respectively) at week 10. In contrast, food intake and growth rate were similar
      for the control, sulindac, and analogue groups. Our results indicate that a
      noncalcemic analogue of vitamin D can significantly decrease intestinal tumor
      load in Apc(min) mice without severe toxic side effects and suggest that these
      compounds may have utility as chemopreventive agents in groups at high-risk for
      colon cancer.

PMID- 11830529
TI  - Interleukin-12 inhibits angiogenesis and growth of transplanted but not in situ
      mouse mammary tumor virus-induced mammary carcinomas.
AB  - We examined the ability of recombinant murine interleukin-12 (rmIL-12) to inhibit
      the vasculature and growth of mammary carcinomas arising in situ in mouse mammary
      tumor virus (MMTV)-infected female C3H/HeN mice. Although it is a potent
      antiangiogenic and antitumor agent in many transplanted murine tumor models, rmIL
      12 failed to inhibit the vascularity, reduce the perfusion, or alter the growth
      of these autochthonous carcinomas. Factors intrinsic to these tumor cells were
      unlikely to be responsible for therapy failure. This is because primary cells
      derived from these carcinomas responded to IFN-gamma, and rmIL-12 was effective
      against transplanted tumors arising from Mm5MT cells, a line established from a
      MMTV-induced mammary carcinoma in C3H mice. Factors intrinsic to the mice that
      host the autochthonous mammary carcinomas were also not responsible for failure,
      because they sponsored rmIL-12 antiangiogenic and antitumor effects against
      transplanted K1735 murine melanoma tumors. Instead, the autochthonous nature of
      the mammary carcinomas and their possession of a high percentage of mature,
      pericyte-covered vessels that are resistant to therapeutic regression may be
      responsible. This is supported by the observation that transplanted Mm5MT tumors
      had a lower proportion of pericyte-covered vessels and responded to rmIL-12
      therapy. These results point to significant differences between the vasculature
      of transplanted and autochthonous murine tumors and indicate that their
      susceptibility to antivascular therapy may differ substantially.

PMID- 11830530
TI  - Suppression of intracranial human glioma growth after intramuscular
      administration of an adeno-associated viral vector expressing angiostatin.
AB  - Despite various therapeutic interventions, glioblastoma multiforme (GBM) is one
      of the most highly vascularized neoplasms in humans with poor prognosis. In this
      study, we show that a single i.m. injection of an adeno-associated viral (AAV)
      vector expressing angiostatin, a potent angiogenic inhibitor, effectively
      suppresses human glioma growth in the brain of nude mice. Approximately 40% of
      the tumor-bearing mice treated with AAV-angiostatin vector survived for >10
      months (the duration of the experiments). In contrast, 100% of the tumor-bearing
      mice in the control groups, with or without i.m. injection of a control vector
      AAV-GFP, died because of excessive tumor burden by 6 weeks. High levels of
      angiostatin produced by the AAV vector were detected in blood circulation for
      >250 days after the one-time vector injection. The secreted angiostatin
      specifically targeted neovessels in the brain tumors, as evidenced by the
      diminished vessel densities and increased apoptosis of tumor cells surrounding
      these neovessels. Our study thus demonstrates that AAV-mediated antiangiogenesis
      gene therapy offers efficient and sustained systemic delivery of the therapeutic
      product, which in turn effectively suppresses glioma growth in the brain.

PMID- 11830531
TI  - Oncolytic activity of the E1B-55 kDa-deleted adenovirus ONYX-015 is independent
      of cellular p53 status in human malignant glioma xenografts.
AB  - Treatment of malignant gliomas remains a major challenge in adults and children
      because of high treatment failure. The E1B 55 kDa-gene deleted adenovirus, ONYX
      015 (ONYX Pharmaceuticals), was demonstrated to replicate selectively in and lyse
      tumor cells. Currently ongoing clinical trials of ONYX-015 in head and neck
      tumors are promising. Here, we demonstrate ONYX-015-mediated cell lysis and
      antitumor activity in three of four s.c. human malignant glioma xenografts
      deriving from primary tumors. Intratumoral injections of ONYX-015, 1 x 10(8)
      plaque-forming units daily for 5 consecutive days, yielded significant tumor
      growth delay in the p53 mutant xenografts IGRG88 and the p53 wild-type IGRG93 and
      IGRG121 treated at an advanced tumor stage. The p53 wild-type tumors IGRG93 and
      IGRG121 experienced 45% and 82% complete tumor regressions. Four and 8 of 11
      animals, respectively, survived tumor free 4 months after treatment. Widespread
      intratumoral adenoviral replication was observed in tumor cells of these two
      xenografts compared with only scattered replication in the p53-mutant tumors. In
      addition to a fast tumor growth rate, wild-type p53 status was associated with
      increased antitumor activity of the E1B-attenuated virus, and induction of
      functional p53 may therefore determine adenoviral cytolysis in tumor cells. In
      conclusion, ONYX-015 displayed a major antitumor activity in human xenografts
      derived from primary malignant glioma supporting its development in the treatment
      of these highly malignant tumors.

PMID- 11830532
TI  - Intratumoral 5-fluorouracil produced by cytosine deaminase/5-fluorocytosine gene
      therapy is effective for experimental human glioblastomas.
AB  - 5-Fluorouracil (5-FU) is a potent antimetabolite used for chemotherapy of
      gastrointestinal (GI), breast, and head and neck malignancies. Although clinical
      trials have been conducted, the poor therapeutic index of 5-FU has precluded its
      clinical use for a number of other tumor types. It is unclear whether this lack
      of utility is due to problems with drug delivery or inherent insensitivity.
      Adenovirus (Ad) vector-mediated cytosine deaminase (CD)/5-fluorocytosine (5-FC)
      gene therapy has the potential to overcome pharmacokinetic issues associated with
      systemic 5-FU and is particularly well suited to use with tumors in which local
      control is paramount, such as recurrent, localized prostate cancer and malignant
      gliomas. In this study, the in vitro response by a panel of human tumor cell
      lines derived from both GI (colon, pancreas) and non-GI (prostate, glioma) tumors
      to 5-FU and to AdCMVCD (an Ad encoding Escherichia coli CD)/5-FC was examined.
      Whereas the sensitivity (IC(50)) of individual cell lines to these agents varied,
      no significant difference in median IC(50) for either 5-FU or AdCMVCD/5-FC was
      evident for the four tumor types tested (P > 0.1). The relevant contributions of
      Ad gene transfer efficiency and inherent 5-FU sensitivity in determining response
      to AdCMVCD/5-FC were then assessed. Multiple linear regression analysis revealed
      that whereas both factors significantly contribute to the response, inherent 5-FU
      sensitivity was substantially more important (beta= 0.78 versus 0.48; P < 0.001).
      Finally, the therapeutic efficacy of a single intratumoral injection of AdCMVCD
      followed by systemic 5-FC was assessed in three intracranial C.B17 severe
      combined immunodeficient mouse models of human glioma. AdCMVCD/5-FC efficacy was
      specific, virus dose-dependent, and closely paralleled in vitro 5-FU and CD/5-FC
      sensitivity in two of three models tested. These results reveal that glioma cells
      are as sensitive as GI tumor cells to the antineoplastic effects of 5-FU,
      identify inherent 5-FU sensitivity as an important factor in determining CD/5-FC
      efficacy, and confirm previous findings in rat models that demonstrate the
      potential clinical utility of AdCMVCD/5-FC gene therapy for gliomas.

PMID- 11830533
TI  - Targeted cytotoxic somatostatin analogue AN-238 inhibits somatostatin receptor
      positive experimental colon cancers independently of their p53 status.
AB  - The resistance of advanced colorectal cancers to therapy is often related to
      mutations in the p53 tumor suppressor gene. Because somatostatin (SRIF) receptors
      (ssts) are present in colorectal carcinomas, the treatment with targeted
      cytotoxic SRIF analogue AN-238, consisting of 2-pyrrolinodoxorubicin (AN-201)
      linked to octapeptide SRIF carrier RC-121, may overcome this resistance by
      producing a higher concentration of the cytotoxic agent in the tumors. Four colon
      cancer cell lines, HCT-116 and LoVo expressing wild-type p53, and HCT-15 and HT
      29 with mutated p53, were investigated. HCT-116, HCT-15, and HT-29, but not LoVo
      possess functional ssts. We analyzed changes in p53, p21, and proliferating cell
      nuclear antigen (PCNA) concentrations in these cells in vitro by immunoblotting
      after exposure to AN-238, its radical AN-201, or doxorubicin (DOX). Equitoxic
      doses of AN-238, AN-201, or DOX affected p53, p21, and PCNA differently. Analysis
      of the p21:p53 ratios revealed that DOX increased p53 levels, but most of p53 was
      mutated and inactive, whereas AN-238 produced smaller changes in p53
      concentrations but enhanced its activity. In HCT-15 cells, PCNA:p21 ratios, which
      are indicators of proliferation and repair processes, remained unchanged after
      exposure to AN-238 but were increased by DOX. In vivo studies in nude mice
      demonstrated that AN-238, AN-201, and DOX were equally effective on HCT-116
      tumors that express wild-type p53. However, AN-238 also inhibited the growth of
      HCT-15 and HT-29 cancers that express mutant p53, whereas AN-201 and DOX showed
      no effect. None of the compounds could suppress the proliferation of LoVo tumors
      that lack functional ssts. In conclusion, cytotoxic SRIF analogue AN-238 inhibits
      the growth of experimental colon cancers that express ssts, regardless of their
      p53 status.

PMID- 11830534
TI  - Antineoplastic effects of chemotherapeutic agents are potentiated by NM-3, an
      inhibitor of angiogenesis.
AB  - Antiangiogenic therapy, although effective in shrinking tumors, has not yet been
      established as a standalone treatment for cancer. This therapeutic limitation can
      be overcome by combining angiogenesis inhibitors with chemotherapeutic agents. NM
      3, a small molecule isocoumarin, is a recently discovered angiogenesis inhibitor.
      Here we demonstrate that NM-3 inhibits the proliferation of human umbilical vein
      endothelial cells in vitro, at concentrations 10-fold less than those required to
      inhibit normal fibroblasts or tumor cells (HT29, MKN28, and MCF-7). NM-3 alone
      inhibits endothelial sprouting and tube formation in vitro. The results also show
      that synergistic antiproliferative activity is observed when human umbilical vein
      endothelial cells are treated with NM-3 in combination with 5-fluorouracil. The
      effects of treatment with NM-3 and various chemotherapeutic agents were also
      evaluated in tumor xenografts. The results demonstrate that combined treatment
      with NM-3 and chemotherapeutic agents significantly reduced mean tumor volume
      compared with either treatment alone, with no effects on body weight changes.
      Taken together, these findings demonstrate that NM-3 is a well-tolerated
      angiogenesis inhibitor that significantly increases the efficacy of existing
      antineoplastic agents.

PMID- 11830535
TI  - Donor leukocyte infusion from immunized donors increases tumor vaccine efficacy
      after allogeneic bone marrow transplantation.
AB  - Donor T cells play a critical role in mediating both harmful graft-versus-host
      disease (GVHD) and beneficial graft-versus-tumor effect after allogeneic bone
      marrow transplantation (BMT). We have recently demonstrated a novel treatment
      strategy to stimulate specific antitumor activity with preservation of tolerance
      to host antigens after T cell-depleted allogeneic BMT by vaccination of
      recipients with irradiated B16 melanoma cells engineered to secrete granulocyte
      macrophage colony-stimulating factor. In this murine system, donor leukocyte
      infusion from a donor immunized with the recipient-derived B16 vaccines enhanced
      clinical activity of tumor vaccines without exacerbating GVHD. CD4(+) T cells are
      essential for this enhancement. In vitro analysis of splenocytes from donor
      leukocyte infusion donor mice demonstrated that immunization of donors with the
      recipient-derived B16 vaccines elicited potent T-cell proliferation and cytokine
      responses specific to B16 antigens. These results demonstrate that immunization
      of donors with recipient-derived tumor vaccines preferentially induces tumor
      specific T-cell responses and that vaccination of both donors and recipients can
      generate potent antitumor immunity without exacerbating GVHD. This strategy has
      important implications to prevent recurrence of malignancies after BMT.

PMID- 11830536
TI  - The CLN3 gene is a novel molecular target for cancer drug discovery.
AB  - Juvenile Batten disease is a neurodegenerative disease caused by accelerated
      apoptotic death of photoreceptors and neurons attributable to defects in the CLN3
      gene. CLN3 is antiapoptotic when overexpressed in NT2 neuronal precursor cells.
      CLN3 negatively modulates endogenous ceramide levels in NT2 cells and acts
      upstream of ceramide generation. Because defects in regulation of apoptosis are
      involved in the development of cancer, we evaluated the expression of CLN3 on
      both mRNA and protein levels in a variety of cancer cell lines and solid colon
      cancer tissue. We also observed the effect of the blocking of CLN3 protein
      expression on cancer cell growth, survival, ceramide production, and apoptosis by
      using an adenovirus-bearing antisense CLN3 construct. We show that CLN3 mRNA and
      protein are overexpressed in glioblastoma (U-373G and T98g), neuroblastoma (IMR
      32 and SK-N-MC), prostate (Du145, PC-3, and LNCaP), ovarian (SK-OV-3, SW626, and
      PA-1), breast (BT-20, BT-549, and BT-474), and colon (SW1116, SW480, and HCT 116)
      cancer cell lines but not in pancreatic (CAPAN and As-PC-1) or lung (A-549 and
      NCI-H520) cancer cell lines. CLN3 is also up-regulated in mouse melanoma and
      breast carcinoma cancer cell lines. We found CLN3 expression is 22-330% higher
      than in corresponding normal colon control tissue in 8 of 10 solid colon tumors.
      An adenovirus-expressing antisense CLN3 (Ad-AS-CLN3) blocks CLN3 protein
      expression in DU-145, BT-20, SW1116, and T98g cancer cell lines as seen by
      Western blot. Blocking of CLN3 expression using Ad-AS-CLN3 inhibits growth and
      viability of cancer cells. It also causes elevation in endogenous ceramide
      production through de novo ceramide synthesis and results in increased apoptosis
      as shown by propidium iodide and JC-1 staining. This suggests that Ad-AS-CLN3 may
      be an option for therapy in some cancers. More importantly these results suggest
      that CLN3 is a novel molecular target for cancer drug discovery.

PMID- 11830537
TI  - Occurrence of chromosome 9 and p53 alterations in multifocal dysplasia and
      carcinoma in situ of human urinary bladder.
AB  - To define the genetic changes of flat urothelial lesions, carcinoma in situ (CIS)
      and moderate dysplasias (DII) were investigated for alterations in the two
      chromosomal regions most frequently involved in bladder cancer. Overall, 33 CIS
      and 16 DII from 21 patients were used to microdissect urothelium. Dual color
      fluorescence in situ hybridization (FISH) using gene locus probes of 9q22 (FACC),
      9p21 (CDK), 17p13 (p53), and related centromeric probes was applied on interphase
      nuclei. In parallel, preamplified DNA of these samples was used for loss of
      heterozygosity (LOH) analyses with eight microsatellite markers on chromosomes
      9p, 9q and 17p, and for sequencing of exons 5-9 of p53. Data indicated nearly
      identical deletion frequencies for chromosomes 9 and 17 for CIS (chromosome 9,
      86%; p53, 84%). DII showed a lower deletion rate in comparison with CIS
      (chromosome 9, 75%; p53, 53%). A very high correlation between the results of
      FISH and LOH analyses was found. p53 mutations were detected in 12 of 15 patients
      (CIS, 72%; DII, 67%). In three of 16 patients with multifocal tumors, oligoclonal
      lesions were identified by LOH analyses, a finding further supported by
      sequencing of p53, by which two different p53 deletions were detected in two
      cases. In conclusion, data from microdissected flat urothelial lesions indicate
      that chromosome 9 deletions cannot be regarded as indicators of papillary growth,
      because they are found frequently in both types of flat lesions of the
      urothelium: those associated with papillary tumors and those that are not. The
      similar distribution and lower amount of genetic changes in DII render DII a
      possible precursor lesion of CIS.

PMID- 11830538
TI  - Relationships and differentially expressed genes among pancreatic cancers
      examined by large-scale serial analysis of gene expression.
AB  - Pancreatic adenocarcinoma is among the most fatal of cancers, in part because of
      late diagnosis and a lack of effective therapies. Comprehensive studies are
      needed to better understand and address the cellular mechanisms and pathways of
      tumorigenesis. Serial analysis of gene expression was used to analyze gene
      expression profiles of pancreatic cancer cell lines, short-term cultures of
      normal pancreatic ductal epithelium, and primary pancreatic cancer tissue. A
      total of 294,920 tags representing 77,746 genes in 10 serial analysis of gene
      expression libraries were analyzed. A pancreatic cancer cell line (Hs766T) that
      exhibited a "normoid" profile of gene expression was identified. Several genes
      that may be involved in the fundamental nature of malignant changes in pancreatic
      ductal epithelium were suggested from those differentially and highly expressed
      in pancreatic cancer cells as compared with normal epithelium. Some overexpressed
      genes, such as S100A4, prostate stem cell antigen, carcinoembryonic antigen
      related cell adhesion molecule 6, and mesothelin, suggest potential use as
      diagnostic markers. Others suggest potential novel therapeutic targets.

PMID- 11830539
TI  - Early Growth Response-1 gene mediates up-regulation of epidermal growth factor
      receptor expression during hypoxia.
AB  - Hypoxia occurs during development of cancers and is correlated with cancer
      progression. Hypoxia also induces epidermal growth factor receptor (EGFR)
      expression. The EGFR plays a vital role in cell growth, and its overexpression
      can lead to transformation. We sought to determine the regulator(s) of EGFR
      expression during hypoxia. We demonstrate that early growth response factor 1
      (Egr-1), which is induced by hypoxia, can activate the basal transcriptional
      activity of the EGFR promoter. Egr-1 not only transactivates the EGFR promoter
      activity but also enhances endogenous EGFR expression. Using a series of EGFR
      promoter deletion mutants, we show that the region between -484 and -389, which
      contains a putative Egr-1 consensus motif, is crucial for EGFR transactivation by
      Egr-1. Electrophoretic mobility shift assays show that Egr-1 binds to the
      oligonucleotide containing this Egr-1 motif. Also, introduction of an antisense
      oligonucleotide for Egr-1 diminishes EGFR expression during hypoxia, indicating
      that the up-regulation of EGFR by hypoxia is mediated through Egr-1. Our results
      provide evidence that regulation of EGFR promoter activity by Egr-1 represents a
      mechanism for epidermal cell growth during hypoxia.

PMID- 11830540
TI  - Interglandular cytogenetic heterogeneity detected by comparative genomic
      hybridization in pancreatic cancer.
AB  - The aim of this study is to explore the mechanisms of intratumoral cytogenetic
      heterogeneity (ICH) in pancreatic cancer. Using comparative genomic hybridization
      (CGH) analysis, we investigated interglandular variation in 20 primary invasive
      ductal adenocarcinomas of the pancreas. Three or four adjacent neoplastic glands
      were individually microdissected from a tumor specimen. Extracted DNA from each
      gland was amplified by degenerate oligonucleotide primed-PCR, followed by CGH. In
      addition, DNA index (DI) was measured by laser scanning cytometry in each case.
      CGH profiles displayed a wide variety of differences between glands within the
      same tumor in all cases, i.e., interglandular cytogenetic heterogeneity was
      distinct in pancreatic cancers. In this study, genetic changes detected in all
      regions of a tumor were classified as "region-independent" alterations, whereas
      changes seen in at least one, but not all regions were designated as "region
      dependent" alterations, which resulted in ICH. The degree of ICH, which was
      manifested as the ratio of these two types of alterations, correlated closely
      with DI (Spearman rho = 0.842; P = 0.0002). Therefore, DI might be a surrogate
      marker for ICH. These results suggest that with tumor progression, ICH and DNA
      aneuploidy result from the successive appearance of region-dependent alterations
      attributable to chromosomal instability in tumor cells. Our data support a
      concept of individual cell heterogeneity in pancreatic cancer.

PMID- 11830541
TI  - Cancer progression and tumor cell motility are associated with the FGFR4 Arg(388)
      allele.
AB  - Expression analysis of genes encoding components of the phosphotyrosine signaling
      system by cDNA array hybridization revealed elevated levels of FGFR4 transcripts
      in several mammary carcinoma cell lines. In the FGFR4 gene transcript from MDA-MB
      453 mammary carcinoma cells, a G to A conversion was discovered that results in
      the substitution of glycine by arginine at position 388 in the transmembrane
      domain of the receptor. The Arg(388) allele was also found in cell lines derived
      from a variety of other tumor types as well as in the germ-line of cancer
      patients and healthy individuals. Analysis of three geographically separated
      groups indicated that it occurs in approximately 50% of the human population.
      Investigation of the clinical data of 84 breast cancer patients revealed that
      homo- or heterozygous carriers of the Arg(388) allele had a significantly reduced
      disease-free survival time (P = 0.01) within a median follow-up of 62 months.
      Moreover, the FGFR4 Arg(388) allele was associated with early lymph node
      metastasis and advanced tumor-node-metastasis (TNM) stage in 82 colon cancer
      patients. Consistent with this finding, MDA-MB-231 mammary tumor cells expressing
      FGFR4 Arg(388) exhibited increased motility relative to cells expressing the
      FGFR4 Gly(388) isotype. Our results support the conclusion that the FGFR4
      Arg(388) allele represents a determinant that is innocuous in healthy individuals
      but predisposes cancer patients for significantly accelerated disease
      progression.

PMID- 11830542
TI  - MSH2 in contrast to MLH1 and MSH6 is frequently inactivated by exonic and
      promoter rearrangements in hereditary nonpolyposis colorectal cancer.
AB  - To estimate the relative frequency of mismatch repair genes, rearrangements in
      hereditary nonpolyposis colorectal cancer (HNPCC) families without detectable
      mutations in MSH2 or MLH1, we have analyzed by multiplex PCR of short fluorescent
      fragments MSH2, MLH1, and MSH6 in 61 families, either fulfilling Amsterdam
      criteria or including cases of multiple primary cancers belonging to the HNPCC
      spectrum. We detected 13 different genomic rearrangements of MSH2 in 14 families
      (23%), whereas we found no rearrangement of MLH1 and MSH6. Analysis of 31 other
      families, partially meeting Amsterdam criteria, revealed no additional
      rearrangement of MSH2. All of the MSH2 rearrangements, except one, corresponded
      to genomic deletions involving one or several exons. In 8 of 13 families with a
      MSH2 genomic deletion, the MSH2 promoter was also deleted, and the 5' breakpoint
      was located either within or upstream the MSH2 gene. This study demonstrates the
      heterogeneity of MSH2 exonic and promoter rearrangements and shows that, in HNPCC
      families without detectable MSH2 or MLH1 point mutation, one must consider the
      presence of MSH2 genomic rearrangements before the involvement of other mismatch
      repair genes. The simplicity and rapidity of their detection, using fluorescent
      multiplex PCR, led us to recommend to begin the molecular analysis in HNPCC by
      screening for MSH2 rearrangements.

PMID- 11830543
TI  - A potential autocrine role for vascular endothelial growth factor in prostate
      cancer.
AB  - Vascular endothelial growth factor (VEGF) is a peptide growth factor specific for
      the tyrosine kinase receptors VEGF receptor-1 and -2 (VEGFR-1 and R-2). Whereas
      VEGF has well-defined actions on the vasculature, including the stimulation of
      endothelial cell growth and motility and blood vessel permeability, the function
      of the VEGF/receptor pathway in other cell types is largely unknown. Recently,
      VEGFR-1 and R-2 expression has been reported in prostate tumor cells. In this
      study, we demonstrate that these receptors colocalize with VEGF in prostate tumor
      cells, prostatic intraepithelial neoplasia, and the basal cells of normal glands.
      Furthermore, in comparison with normal glands, the expression of VEGFR-1 and R-2
      is increased in prostatic intraepithelial neoplasia and malignant cells in well
      and moderately differentiated prostate cancer but is decreased in poorly
      differentiated cancer. Culture of the prostate cancer cell line LNCaP in the
      presence of recombinant human VEGF165 resulted in a 50% increase in
      [(3)H]thymidine uptake by these cells and recruitment of quiescent cells into the
      cell cycle. This effect of recombinant human VEGF165 was abolished by
      neutralizing antisera to VEGFR-2. These data suggest that VEGF may not only
      mediate neovascularization associated with prostate cancer progression but may
      also directly stimulate prostate tumor cells via VEGFR-2-dependent autocrine
      and/or paracrine mechanisms.

PMID- 11830544
TI  - Rapid accumulation and internalization of radiolabeled herceptin in an
      inflammatory breast cancer xenograft with vasculogenic mimicry predicted by the
      contrast-enhanced dynamic MRI with the macromolecular contrast agent G6-(1B4M
      Gd)(256).
AB  - The rapid blood flow and perfusion of macromolecules in the inflammatory breast
      cancer xenograft (WIBC-9), which exhibits a "vasculogenic mimicry" type of
      angiogenesis without the participation of endothelial cells and expresses high
      levels of the HER-2/neu antigen, was evaluated in mice using 3D-micro-MR
      angiography using a novel macromolecular MR contrast agent [G6-(1B4M-Gd)(256)].
      Herceptin, which recognizes the HER-2/neu antigen and has similar size (10 nm) to
      G6-(1B4M-Gd)(256), accumulated and internalized in the WIBC-9 tumors more quickly
      than in the control MC-5 tumors that progress with normal angiogenesis. Three
      dimensional micro-MRI with the G6-(1B4M-Gd)(256) macromolecular MRI contrast
      agent distinguishes between the different types of angiogenesis and is predictive
      of the rapid accumulation and internalization of Herceptin in the WIBC-9
      inflammatory breast cancer xenograft.

PMID- 11830545
TI  - Differential binding of drugs containing the NGR motif to CD13 isoforms in tumor
      vessels, epithelia, and myeloid cells.
AB  - The NGR peptide motif is an aminopeptidase N (CD13) ligand that targets
      angiogenic blood vessels. NGR-containing peptides have proven useful for
      delivering cytotoxic drugs, proapoptotic peptides, and tumor necrosis factor
      alpha(TNF) to tumor vasculature. Given that CD13 is not only expressed in the
      angiogenic endothelium but also in other cell types, the mechanism(s) for the
      tumor-homing properties of NGR-drug conjugates remains elusive. We have examined
      the expression of CD13 in normal and neoplastic human tissues and cells by using
      two anti-CD13 monoclonal antibodies. The immunoreactivity patterns obtained with
      cultured cells and tissue sections from kidney, breast, and prostate carcinomas
      suggest that different CD13 forms are expressed in myeloid cells, epithelia, and
      tumor-associated blood vessels. Both, direct binding assays with a CNGRCG-TNF
      conjugate (NGR-TNF) and competitive inhibition experiments with anti-CD13
      antibodies showed that a CD13 isoform expressed in tumor blood vessels could
      function as a vascular receptor for the NGR motif. In contrast, CD13 expressed in
      normal kidney and in myeloid cells failed to bind to NGR-TNF. Consistently with
      these results, neither murine(125)I-NGR-TNF nor (125)I-TNF accumulated in normal
      organs containing CD13-expressing cells after administration to mice. These
      findings may explain the selectivity and the tumor-homing properties of NGR-drug
      conjugates and may have important implications in the development of vascular
      targeted therapies based on the NGR/CD13 system.

PMID- 11830546
TI  - Alpha-melanocyte stimulating hormone potentiates p16/CDKN2A expression in human
      skin after ultraviolet irradiation.
AB  - The contribution of the UV component of sunlight to the development of skin
      cancer is widely acknowledged, although the molecular mechanisms that are
      disrupted by UV radiation (UVR) resulting in the loss of normal growth controls
      of the epidermal stem cell keratinocytes and melanocytes is still poorly
      understood. Alpha-melanocyte stimulating hormone (alpha-MSH), acting via its
      receptor MC1, has a key role in skin pigmentation and the melanizing response
      after exposure to UVR. The cell cycle inhibitor p16/CDKN2A also appears to have
      an important function in a cell cycle checkpoint response in skin after exposure
      to UVR. Both of these genes have been identified as risk factors in skin cancer,
      MC1R variants are associated with increased risk to both melanoma and nonmelanoma
      skin cancers, and p16/CDKN2A with increased risk of melanoma. Here we demonstrate
      that the increased expression of p16 after exposure to suberythemal doses of UVR
      is potentiated by alpha-MSH, a ligand for MC1R, and this effect is mimicked by
      cAMP, the intracellular mediator of alpha-MSH signaling via the MC1 receptor.
      This link between p16 and MC1R may provide a molecular basis for the increased
      skin cancer risk associated with MC1R polymorphisms.

PMID- 11830547
TI  - Progesterone inhibits human endometrial cancer cell growth and invasiveness: down
      regulation of cellular adhesion molecules through progesterone B receptors.
AB  - Progesterone is a critical steroid hormone that controls cell proliferation and
      differentiation in the female reproductive tract. Progesterone acts through two
      nuclear receptor isoforms, progesterone receptors A and B (PRA and PRB,
      respectively), each with unique cellular effects. Loss of PRB has recently been
      linked to the development of poorly differentiated endometrial tumors, a lethal
      form of cancer. To study the molecular effects of progesterone, progesterone
      receptors were introduced into Hec50co endometrial cancer cells by adenoviral
      vectors encoding either PRA or PRB. Progesterone induced the cyclin-dependent
      kinase inhibitors p21 and p27, thereby significantly reducing the percentage of
      proliferating cells. Cancer cell invasion was also markedly inhibited as measured
      by Matrigel invasion studies. Similarly, a differentiated, secretory phenotype
      was induced by progesterone in cells expressing PRB. However, replicative
      senescence was induced by progesterone only in cells expressing PRA. Expression
      array analysis followed by confirmatory semiquantitative reverse transcription
      PCR experiments demonstrated a significant progesterone-dependent inhibition of
      expression of a cadre of cellular adhesion molecules, including fibronectin,
      integrin alpha3, integrin beta1, integrin beta3, and cadherin 6. The level of
      down-regulation of adhesion molecule expression was significantly greater in the
      presence of the B isoform, demonstrating that progesterone acts principally
      through B receptors to inhibit cancer cell invasiveness modulated by adhesion
      molecules.

PMID- 11830548
TI  - Activated ras regulates the proliferation/apoptosis balance and early survival of
      developing micrometastases.
AB  - Mutant, activated ras oncogenes are found in many human cancers. Experimental
      studies have shown that Ras enhances metastatic ability in several cell types.
      However, the biological mechanisms by which Ras contributes to metastasis remain
      poorly understood. Our goal was to determine which steps in the formation of
      macroscopic metastases were affected by Ras. Green fluorescent protein
      transfected NIH 3T3 and T24 H-ras-transformed (PAP2) fibroblasts were injected
      via mesenteric vein to target mouse liver. The proportion of cells that survived
      at each step of the metastatic process (at 60 min to 14 days after injection)
      were quantified. We found that Ras did not enhance the ability of cells to
      extravasate from liver sinusoids or to survive as solitary undivided cells in
      liver tissue. Furthermore, we found that a subset of cells from both cell lines
      initiated growth to form micrometastases by day 3. Only micrometastases formed by
      ras-transformed cells, however, persisted to form macroscopic metastases by day
      14, whereas most NIH 3T3 micrometastases disappeared. We investigated this
      difference in maintenance of developing metastases by quantifying apoptosis and
      proliferation within the micrometastases. PAP2 metastases had a significantly
      higher proportion of proliferating cells as compared with apoptosing cells,
      whereas NIH 3T3 metastases had low proliferation and high apoptosis levels.
      Whereas the ability of Ras to induce vascular endothelial growth factor has
      suggested one way that Ras might affect metastatic ability (through induction of
      angiogenesis), our study provides in vivo evidence for a direct role for Ras in
      maintenance of metastatic growth via a shift in proliferation/apoptosis balance
      to favor metastatic growth.

PMID- 11830549
TI  - An MCL1-overexpressing Burkitt lymphoma subline exhibits enhanced survival on
      exposure to serum deprivation, topoisomerase inhibitors, or staurosporine but
      remains sensitive to 1-beta-D-arabinofuranosylcytosine.
AB  - Members of the BCL2 gene family influence cell viability and can, therefore,
      affect the susceptibility of cancer cells to multiple chemotherapeutic agents.
      Thus, it is a challenge to devise approaches for inducing the death of tumor
      cells in which the expression of prosurvival family members is elevated or
      deregulated. BL41-3, a spontaneously derived subline of BL41 Burkitt lymphoma
      cells, was found to have amplified the prosurvival MCL1 gene (3-fold) and
      overexpressed the MCL1 protein. The level of MCL1 protein was 5-fold elevated
      compared with ML-1 cells expressing maximal MCL1 on exposure to phorbol-12
      myristate-13- acetate. To assess whether this increase in MCL1 expression was
      associated with enhanced protection from cell death, cells were exposed to
      conditions of growth factor deprivation or to various cytotoxic agents. Whereas
      BL41-3 and BL41 cells exhibited similar growth rates in logarithmic phase, BL41-3
      cells remained largely viable on reaching saturation phase in contrast to BL41
      cells, which began to die. Similarly, the BL41-3 subline remained viable for an
      extended period under conditions of reduced serum. BL41-3 cells were also more
      resistant to the apoptosis-inducing effects of etoposide, camptothecin, and
      staurosporine (>3-fold more than BL41 cells). Unexpectedly, these cells exhibited
      enhanced sensitivity to 1-beta-D-arabinofuranosylcytosine, but only on exposure
      for an extended period (>10-fold more sensitive than BL41 cells with a 24-h but
      not a 6-h exposure). Thus, whereas cells expressing prosurvival BCL2 family
      members are frequently resistant to a variety of chemotherapeutic agents, the
      findings presented here, using a cell line exhibiting amplification and
      overexpression of MCL1, indicate that such cells may exhibit increased
      sensitivity to certain chemotherapeutic regimens.

PMID- 11830550
TI  - High incidence of T-cell lymphomas in mice deficient in the retinoid-related
      orphan receptor RORgamma.
AB  - Nuclear receptors are critical regulators of many physiological processes and
      have been shown to be involved in a variety of disease processes, including
      malignant neoplasms. Our laboratory is investigating the function of the retinoid
      related orphan receptor gamma (RORgamma) and its possible role in disease.
      Studies of mice deficient in the expression of RORgamma demonstrated that this
      receptor plays a crucial role in the regulation of thymopoiesis and lymph node
      organogenesis. In this study, we show that changes in homeostasis in the thymus
      of RORgamma-/- mice are associated with a high incidence of T-cell lymphomas.
      Over 50% of the deficient mice of mixed genetic background die within the first 4
      months as a result of thymic lymphomas. A high incidence of lymphomas was also
      observed in RORgamma-/- 129/SvEv mice. The lymphoblastic cells metastasized
      frequently to spleen and liver. No other tumor types were detected in any of
      RORgamma-/- mice that died during the course of the experiment, and none of the
      heterozygous mice developed thymic lymphomas. Lymphoma formation was associated
      with increased cellular proliferation and an increase in the number of apoptotic
      cells. When placed in culture, the RORgamma-/- lymphoblastic cells underwent
      accelerated "spontaneous" apoptosis at a rate similar to that of RORgamma-/-
      thymocytes. Upon prolonged culture, several lymphoblastic cell lines could be
      established. Analysis of the immunophenotype of the lymphoblastic cells showed
      that the CD4 and CD8 subpopulations varied substantially among different
      lymphomas. The established cell lines consisted mostly of CD44-CD25+CD4-CD8-
      cells. Our studies indicate that loss of RORgamma disturbs homeostasis in the
      thymus by enhancing apoptosis and cellular proliferation. The latter may enhance
      the probability of individual cells to acquire genetic alterations that make them
      escape negative selection and normal differentiation programs and as a
      consequence lead to increased susceptibility to the development of T-cell
      lymphoma.

PMID- 11830551
TI  - Autocrine production of interleukin 1beta confers constitutive nuclear factor
      kappaB activity and chemoresistance in pancreatic carcinoma cell lines.
AB  - We have recently shown that several pancreatic carcinoma cell lines are resistant
      to topoisomerase IIalpha inhibitors due to elevated basal nuclear factor kappaB
      (NF-kappaB) activity, and blockade of this activity by various means strongly
      increased chemosensitivity. In search of possible mechanisms leading to
      exaggerated NF-kappaB activity, we identified interleukin (IL)-1beta as a key
      mediator of this activation in two of the chemoresistant cell lines (A818-4 and
      PancTu-1). These cells express and secrete high levels of IL-1beta, as
      demonstrated by reverse transcription-PCR, immunocytochemistry, and ELISA.
      Culture supernatants from both cell lines induced NF-kappaB activity in
      chemosensitive PT45-P1 pancreatic carcinoma cells and significantly attenuated
      etoposide-induced apoptosis in a NF-kappaB-dependent fashion, similar to that
      seen in PT45-P1 cells treated with recombinant IL-1beta. Treatment of these cells
      with IL-1beta also changed the DNA damage characteristics toward those observed
      in A818-4 and PancTu-1 cells. NF-kappaB activation and the gain of
      chemoresistance in PT45-P1 cells on treatment with supernatants from both
      chemoresistant cell lines was abolished in the presence of a blocking anti-IL-1
      receptor (I) antibody. Furthermore, this antibody decreased the resistance of
      A818-4 and PancTu-1 cells to etoposide treatment along with reduced NF-kappaB
      activity. Blockade of NF-kappaB activation by MG132, sulfasalazine, or an
      IkappaBalpha superrepressor disrupted the IL-1beta-mediated amplification loop
      and the accompanying chemoresistance. Our data provide insights into an autocrine
      mechanism involving IL-1beta by which pancreatic carcinoma cells develop
      chemoresistance that could serve as a molecular target in anticancer therapy.

PMID- 11830552
TI  - Tumor-derived platelet-derived growth factor-BB plays a critical role in
      osteosclerotic bone metastasis in an animal model of human breast cancer.
AB  - Breast cancer produces a variety of growth factors to promote its behavior at
      primary and secondary sites in autocrine/paracrine manners. However, the role of
      these growth factors in the colonization of cancer cells in bone, which is one of
      the most common metastatic sites, is poorly understood. To study this, we
      established an in vivo model in which the MCF-7 human breast cancer cells caused
      predominant osteosclerotic bone metastases 20-25 weeks after inoculation into the
      left cardiac ventricle in female nude mice. To make this model more time
      efficient, we overexpressed the oncogene Neu, which is associated with aggressive
      behavior in human breast cancers, in MCF-7 cells (MCF-7/Neu). MCF-7/Neu cells
      grew without estrogen and developed osteosclerotic bone metastases in 10-12 weeks
      in animals. Of note, MCF-7/Neu-bearing mice showed substantial plasma levels of
      human platelet-derived growth factor-BB (hPDGF-BB; 855 +/- 347 pg/ml; mean +/-
      SE, n = 5), indicating hPDGF-BB production by inoculated MCF-7/Neu cells. MCF
      7/Neu cells in culture also produced large amounts of hPDGF-BB. Conditioned
      medium harvested from MCF-7/Neu cells stimulated osteoblastic bone formation in
      organ cultures of neonatal mouse calvariae, and a neutralizing antibody to hPDGF
      BB blocked the osteoblastic bone formation. Stable transfection of the hPDGF-B AS
      in MCF-7/Neu cells reduced hPDGF-BB production in culture. Mice bearing these MCF
      7/Neu cells with antisense showed reduced bone metastases with decreased plasma
      hPDGF-BB levels (54 +/- 20 and 35 +/- 21 in two different antisense and 696 +/-
      312 pg/ml in empty vector; mean +/- SE; n = 5). Introduction of hPDGF-B cDNA in
      the MDA-MB-231 human breast cancer cells, which consistently formed osteolytic
      bone metastases, induced osteosclerotic lesions in the osteolytic bone
      metastases. In conclusion, we show that MCF-7 cells cause osteosclerotic bone
      metastases and that Neu enhances this capacity of MCF-7 cells. Our data suggest
      that MCF-7/Neu-derived hPDGF-BB plays a causative role in the development of
      osteosclerotic bone metastases in this model.

PMID- 11830553
TI  - Dysfunctional apoptosome activation in ovarian cancer: implications for
      chemoresistance.
AB  - Alterations in the regulation of apoptosis may contribute to the pathogenesis of
      cancer and resistance of tumor cells to chemotherapy. In mammalian cells,
      nonreceptor-mediated apoptosis occurs predominantly via assembly of a cytochrome
      c-dependent apoptosome complex containing caspase-9 and apoptotic protease
      activating factor-1 (Apaf-1). We show here that cytosolic extracts from human
      ovarian carcinoma cell lines and primary ovarian tumor samples are deficient in
      their ability to activate procaspase-9 in the presence of cytochrome c and dATP
      when compared with control extracts. SKOV3, a human ovarian carcinoma cell line
      with diminished apoptosome activity, was significantly more resistant to
      chemotherapy-induced apoptosis than cell lines with functional Apaf-1 activity.
      This dysfunctional apoptosome activity was not explained by reduced expression
      levels of caspase-9 or Apaf-1. Moreover, expression levels of known inhibitors of
      the apoptosome, including heat shock protein 70, heat shock protein 90, or X
      linked inhibitor of apoptosis, did not correlate with functional activity of the
      apoptosome. SKOV3, an ovarian cancer cell line with dysfunctional apoptosome
      activity, retains the ability to form the Apaf-1 oligomer; however, there is a
      diminished amount of caspase-9 in the apoptosome. The reduction in the amount of
      caspase-9 in the apoptosome in the SKOV3 cell line was associated with diminished
      caspase-3 activity. Dysfunctional apoptosome activation may contribute both to
      the pathogenesis of ovarian carcinoma and to chemoresistance.

PMID- 11830554
TI  - Autocrine interleukin-6 production in renal cell carcinoma: evidence for the
      involvement of p53.
AB  - Interleukin (IL)-6 is an autocrine growth factor for renal cell carcinoma (RCC).
      We sought to determine whether p53 regulates constitutive IL-6 production. RCC
      cell lines containing mutant (mut) p53 produced higher levels of IL-6 than those
      containing wild-type (wt) p53 (P < 0.05). Transfection of wt p53 into RCC cell
      lines bearing mut p53 (UOK 121LN) or wt p53 (A498 and ACHN) resulted in
      repression of IL-6 promoter chloramphenicol acetyltransferase activity (P <
      0.05). Mutant p53 was either less effective at repressing IL-6 promoter activity
      (ACHN cells) or enhanced IL-6 promoter activity (A498 cells). A498 cells stably
      transfected with mut p53 produced higher levels of IL-6 than A498 cells
      transfected with an empty expression vector (P < 0.05). Electrophoretic mobility
      shift assays showed decreased binding of CAAT enhancer binding protein, cyclic
      AMP responsive element binding protein, +/- nuclear factor-kappaB transcription
      factors to the IL-6 promoter in various RCC cell lines transfected with wt p53 (P
      < 0.05) but not in those transfected with mut p53. These data suggest that: (a)
      mutation of p53 contributes to the overexpression of IL-6 in RCC; and (b) wt p53
      represses IL-6 expression, at least in part, by interfering with specific
      transcription factor binding to the IL-6 promoter.

PMID- 11830555
TI  - Chromogranin A expression in neoplastic cells affects tumor growth and
      morphogenesis in mouse models.
AB  - Chromogranin A (CgA), a secretory protein expressed by many neuroendocrine cells,
      has been recognized as a useful tissue and serum marker of neuroendocrine tumors.
      To investigate the effect of CgA secretion on neoplastic morphogenesis and
      progression, we have transfected mouse RMA lymphoma and TS/A adenocarcinoma cells
      with the cDNA encoding human CgA and selected several CgA-positive (secreting)
      and CgA-negative (nonsecreting) clones. In both models, the growth rate of CgA
      positive clones implanted s.c. in nude mice was slower than that of CgA-negative
      clones. Histological analysis of each RMA tumor showed that CgA-expression was
      associated with multinodular growth patterns, whereas CgA-negative tumors
      appeared more compact and similar to wild-type RMA tumors. Moreover, CgA
      production was associated with increased tumor necrosis. The number of nodules in
      each RMA tumor correlated with the serum levels of CgA (n = 40, r = 0.537, P =
      0.0004). The reduced growth rate of CgA-positive RMA and TS/A tumors was not
      related to reduced in vitro proliferation or to changes in cell adhesion and
      shape, suggesting that the mechanism is indirect and host-mediated. These results
      suggest that abnormal secretion of CgA by neuroendocrine neoplastic cells could
      affect neoplastic growth and morphogenesis.

PMID- 11830556
TI  - A misspliced form of the cholecystokinin-B/gastrin receptor in pancreatic
      carcinoma: role of reduced sellular U2AF35 and a suboptimal 3'-splicing site
      leading to retention of the fourth intron.
AB  - Abnormal splicing of primary RNA transcripts of normal genes is a recognized
      mechanism for the production of some abnormal proteins found in cancer cells. A
      misspliced form of the cholecystokinin-B/gastrin (CCK-B) receptor recently was
      reported to be present in colon carcinoma, where it was postulated to play a role
      in stimulating tumor growth (M. R. Hellmich et al., J. Biol. Chem., 275: 32122
      32128, 2000). Here, we report the presence of the same abnormal protein in
      pancreatic carcinoma and explore the molecular basis for this missplicing event.
      Reverse transcription-PCR and sequencing were used to demonstrate the presence of
      a misspliced form of the CCK-B receptor having its fourth intron retained in
      three pancreatic cancer cell lines and in tumor tissue, but not in surrounding
      healthy pancreas, from two patients with pancreatic carcinoma. A mini-gene
      construct representing the region of this gene from its third through its fifth
      exon and containing the two intervening introns was produced and transiently
      expressed in the MIA PaCa-2 human pancreatic cancer cell line. Specific reverse
      transcription-PCR reactions with both vector-derived and receptor-specific
      primers demonstrated the presence of both correctly fully spliced and selectively
      misspliced forms of this receptor. Mutagenesis of the mini-gene demonstrated that
      a suboptimal sequence at the 3'-end of intron 4 contributed to this missplicing.
      This focused attention on the U2 small nuclear ribonucleoprotein particle
      auxiliary splicing factors (U2AFs) known to interact specifically with this
      domain. Indeed, quantitative real-time PCR demonstrated a reduced level of
      expression of one of these factors, U2AF35, in pancreatic cancer cells compared
      with healthy pancreas. Furthermore, the relative amount of missplicing of the CCK
      B receptor mini-gene in the pancreatic cancer cell line was reversed by
      transfection of the cells with U2AF35 cDNA. This work describes the presence of
      an additional abnormal protein in pancreatic cancer and describes a new molecular
      mechanism for its production, providing additional potential therapeutic targets.

PMID- 11830558
TI  - scute expression in Calliphora vicina reveals an ancestral pattern of
      longitudinal stripes on the thorax of higher Diptera.
AB  - In Drosophila the stereotyped arrangement of sensory bristles on the notum is
      determined by the tightly regulated control of transcription of the achaete-scute
      (ac-sc) genes which are expressed in small proneural clusters of cells at the
      sites of each future bristle. Expression relies on a series of discrete cis
      regulatory elements present in the ac-sc gene complex that are the target of the
      transcriptional activators pannier (pnr) and the genes of the iroquois complex.
      Stereotyped bristle patterns are common among species of acalyptrate Schizophora
      such as Drosophila, and are thought to have derived from an ancestral pattern of
      four longitudinal rows extending the length of the scutum, through secondary loss
      of bristles. To investigate evolutionary changes in bristle patterns and ac-sc
      regulation by pnr, we have isolated homologues of these genes from Calliphora
      vicina, a species of calyptrate Schizophora separated from Drosophila by at least
      100 million years. Calliphora vicina displays a pattern of four rows of bristles
      on the scutum resembling the postulated ancestral one. We find that sc in
      Calliphora is expressed in two longitudinal stripes on the medial scutum that
      prefigure the development of the rows of acrostichal and dorsocentral bristles.
      This result suggests that a stripe-like expression pattern of sc may be an
      ancestral feature and may have preceded the evolution of proneural clusters. The
      implications for the evolution of the cis-regulatory elements responsible for sc
      expression in the proneural clusters of Drosophila, and function of Pnr are
      discussed.

PMID- 11830557
TI  - Tail gut endoderm and gut/genitourinary/tail development: a new tissue-specific
      role for Hoxa13.
AB  - Hoxa13 is expressed early in the caudal mesoderm and endoderm of the developing
      hindgut. The tissue-specific roles of Hoxa13 function have not been described.
      Hand-foot-genital syndrome, a rare dominantly inherited human malformation
      syndrome characterized by distal extremity and genitourinary anomalies, is caused
      by mutations in the HOXA13 gene. We show evidence that one specific HOXA13
      mutation likely acts as a dominant negative in vivo. When chick HFGa13 is
      overexpressed in the chick caudal endoderm early in development, caudal
      structural malformations occur. The phenotype is specific to HFGa13 expression in
      the posterior endoderm, and includes taillessness and severe gut/genitourinary
      (GGU) malformations. Finally, we show that chick HFGa13 negatively regulates
      expression of Hoxd13 and antagonizes functions of both endogenous Hoxa13 and
      Hoxd13 proteins. We suggest a fundamental role for epithelial specific expression
      of Hoxa13 in the epithelial-mesenchymal interaction necessary for tail growth and
      posterior GGU patterning.

PMID- 11830560
TI  - Meis family proteins are required for hindbrain development in the zebrafish.
AB  - Meis homeodomain proteins function as Hox-cofactors by binding Pbx and Hox
      proteins to form multimeric complexes that control transcription of genes
      involved in development and differentiation. It is not known what role Meis
      proteins play in these complexes, nor is it clear which Hox functions require
      Meis proteins in vivo. We now show that a divergent Meis family member, Prep1,
      acts as a Hox co-factor in zebrafish. This suggests that all Meis family members
      have at least one shared function and that this function must be carried out by a
      conserved domain. We proceed to show that the Meinox domain, an N-terminal
      conserved domain shown to mediate Pbx binding, is sufficient to provide Meis
      activity to a Pbx/Hox complex. We find that this activity is separable from Pbx
      binding and resides within the M1 subdomain. This finding also presents a
      rational strategy for interfering with Meis activity in vivo. We accomplish this
      by expressing the Pbx4/Lzr N-terminus, which sequesters Meis proteins in the
      cytoplasm away from the nuclear transcription complexes. Sequestering Meis
      proteins in the cytoplasm leads to extensive loss of rhombomere (r) 3- and r4
      specific gene expression, as well as defective rhombomere boundary formation in
      this region. These changes in gene expression correlate with impaired neuronal
      differentiation in r3 and r4, e.g. the loss of r3-specific nV branchiomotor
      neurons and r4-specific Mauthner neurons. We conclude that Meis family proteins
      are essential for the specification of r3 and r4 of the hindbrain.

PMID- 11830559
TI  - Distinct regulatory cascades for head and trunk myogenesis.
AB  - Most head muscles arise from the pre-otic axial and paraxial head mesoderm. This
      tissue does not form somites, yet expresses the somitic markers Lbx1, Pax7 and
      Paraxis in a regionalised fashion. The domain set aside by these markers provides
      the lateral rectus muscle, the most caudal of the extrinsic eye muscles. In
      contrast to somitic cells that express Lbx1, lateral rectus precursors are non
      migratory. Moreover, the set of markers characteristic for the lateral rectus
      precursors differs from the marker sets indicative of somitic muscle precursors.
      This suggests distinct roles for Lbx1/Pax7/Paraxis in the development of head and
      trunk muscles. When grafted to the trunk, the pre-otic head mesoderm fails to
      activate Lbx1, Pax7 or PARAXIS: Likewise, somites grafted into the region of the
      lateral rectus precursors fail to activate the lateral rectus marker set. This
      suggests that distinct regulatory cascades act in the development of trunk and
      head muscles, possibly reflecting their distinct function and evolution.

PMID- 11830561
TI  - Postembryonic development of the posterior lateral line in zebrafish.
AB  - We examine how the posterior lateral line of the zebrafish grows and evolves from
      the simple midbody line present at the end of embryogenesis into the complex
      adult pattern. Our results suggest that secondary neuromasts do not form through
      budding from the embryonic line, but rather new waves of neuromasts are added
      anteroposteriorly. We propose that the developmental module that builds the
      embryonic pattern of neuromasts is used repeatedly during postembryonic
      development and that additional (secondary) primordia generate the additional
      neuromasts. We show that differentiated neuromasts migrate ventrally, and
      eventually generate "stitches" by successive bisections. We also examine the
      repatterning of the terminal neuromasts, which anticipates the up-bending of the
      tail leading to the highly asymmetrical caudal fin of the adult (which develops
      exclusively from the ventral part of the tail). Because terminal repatterning
      affects all aspects of tail formation, including its sensory development, we
      speculate that terminal axis bending may have become intimately associated with
      the terminal Hox genes before the appearance of the tetrapod lineage.

PMID- 11830562
TI  - Cell migration in the postembryonic development of the fish lateral line.
AB  - We examine at the cellular level the postembryonic development of the posterior
      lateral line in the zebrafish. We show that the first wave of secondary
      neuromasts is laid down by a migrating primordium, primII. This primordium
      originates from a cephalic region much like the primordium that formed the
      primary line during embryogenesis. PrimII contributes to both the lateral and the
      dorsal branches of the posterior lateral line. Once they are deposited by the
      primordium, the differentiating neuromasts induce the specialisation of overlying
      epidermal cells into a pore-forming annulus, and the entire structure begins to
      migrate ventrally across the epithelium. Thus the final two-dimensional pattern
      depends on the combination of two orthogonal processes: anteroposterior waves of
      neuromast formation and dorsoventral migration of individual neuromasts. Finally,
      we examine how general these migratory processes can be by describing two fish
      species with very different adult patterns, Astyanax fasciatus (Mexican blind
      cavefish) and Oryzias latipes (medaka). We show that their primary patterns are
      nearly identical to that observed in zebrafish embryos, and that their
      postembryonic growth relies on the same combination of migratory processes that
      we documented in the case of the zebrafish.

PMID- 11830563
TI  - Persistent larval sensory neurones are required for the normal development of the
      adult sensory afferent projections in Drosophila.
AB  - We have tested the hypothesis that larval neurones guide growth of adult sensory
      axons in Drosophila. We show that ablation of larval sensory neurones causes
      defects in the central projections of adult sensory neurones. Spiralling axons
      and ectopic projections indicate failure in axon growth guidance. We show that
      larval sensory neurones are required for peripheral pathfinding, entry into the
      CNS and growth guidance within the CNS. Ablation of subsets of neurones shows
      that larval sensory neurones serve specific guidance roles. Dorsal neurones are
      required for axon guidance across the midline, whereas lateral neurones are
      required for posterior growth. We conclude that larval sensory neurones pioneer
      the assembly of sensory arrays in adults.

PMID- 11830564
TI  - Differential interactions of eyeless and twin of eyeless with the sine oculis
      enhancer.
AB  - Drosophila eye development is under the control of early eye specifying genes
      including eyeless (ey), twin of eyeless (toy), eyes absent (eya), dachshund (dac)
      and sine oculis (so). They are all conserved between vertebrates and insects and
      they interact in a combinatorial and hierarchical network to regulate each other
      expression. so has been shown to be directly regulated by ey through an eye
      specific enhancer (so10). We further studied the regulation of this element and
      found that both Drosophila Pax6 proteins namely EY and TOY bind and positively
      regulate so10 expression through different binding sites. By targeted mutagenesis
      experiments, we disrupted these EY and TOY binding sites and studied their
      functional involvement in the so10 enhancer expression in the eye progenitor
      cells. We show a differential requirement for the EY and TOY binding sites in
      activating so10 during the different stages of eye development. Additionally, in
      a rescue experiment performed in the so(1) mutant, we show that the EY and TOY
      binding sites are required for compound eye and ocellus development respectively.
      Altogether, these results suggest a differential requirement for EY and TOY to
      specify the development of the two types of adult visual systems, namely the
      compound eye and the ocellus.

PMID- 11830565
TI  - The murine seminiferous epithelial cycle is pre-figured in the Sertoli cells of
      the embryonic testis.
AB  - The seminiferous epithelial cycle and spermatogenic wave are conserved features
      of vertebrate spermatogenic organisation that reflect the need for the rigorous
      maintenance of sperm production. Although the cycle and the wave of the adult
      seminiferous epithelium have been well characterised, particularly in rodent
      species, their developmental origins are unknown. We show that the Sertoli cells
      of the pre-pubertal mouse, including those of the germ cell-deficient XXSxra
      mutant, exhibit coordinated, cyclical patterns of gene expression, presaging the
      situation in the adult testis, where Sertoli cell function is coupled to the
      spermatogenic cycle. In the case of the galectin 1 gene (Lgals1), localised
      differential expression in the Sertoli cells can be traced back to neonatal and
      embryonic stages, making this the earliest known molecular marker of functional
      heterogeneity in mammalian testis cords. In addition, the timing of germ cell
      apoptosis in normal pre-pubertal testes is linked to the temporal cycle of the
      Sertoli cells. These data show that the cycle and wave of the murine seminiferous
      epithelium originate at a much earlier stage in development than was previously
      known, and that their maintenance in the early postnatal cords depends
      exclusively on the somatic cell lineages.

PMID- 11830566
TI  - Non-cell autonomous requirement for the bloodless gene in primitive hematopoiesis
      of zebrafish.
AB  - Vertebrate hematopoiesis occurs in two distinct phases, primitive (embryonic) and
      definitive (adult). Genes that are required specifically for the definitive
      program, or for both phases of hematopoiesis, have been described. However, a
      specific regulator of primitive hematopoiesis has yet to be reported. The
      zebrafish bloodless (bls) mutation causes absence of embryonic erythrocytes in a
      dominant but incompletely penetrant manner. Primitive macrophages appear to
      develop normally in bls mutants. Although the thymic epithelium forms normally in
      bls mutants, lymphoid precursors are absent. Nonetheless, the bloodless mutants
      can progress through embryogenesis, where red cells begin to accumulate after 5
      days post-fertilization (dpf). Lymphocytes also begin to populate the thymic
      organs by 7.5 dpf. Expression analysis of hematopoietic genes suggests that
      formation of primitive hematopoietic precursors is deficient in bls mutants and
      those few blood precursors that are specified fail to differentiate and undergo
      apoptosis. Overexpression of scl, but not bmp4 or gata1, can lead to partial
      rescue of embryonic blood cells in bls. Cell transplantation experiments show
      that cells derived from bls mutant donors can differentiate into blood cells in a
      wild-type host, but wild-type donor cells fail to form blood in the mutant host.
      These observations demonstrate that the bls gene product is uniquely required in
      a non-cell autonomous manner for primitive hematopoiesis, potentially acting via
      regulation of scl.

PMID- 11830567
TI  - Formation of a large Vasa-positive germ granule and its inheritance by germ cells
      in the enigmatic Chaetognaths.
AB  - Chaetognaths (arrow worms) are abundant hermaphrodite marine organisms whose
      phylogenetic position amongst protostomes and deuterostomes is still debated.
      Ancient histological observations dating from a century ago described the
      presence in eggs of a large granule, presumed to be a germ plasm, and its
      probable inheritance in four primary germ cells (PGCs). Using videomicroscopy,
      electron microscopy and immunocytochemistry (labelling with anti-Vasa antibodies)
      we have followed the cycle of aggregation and dispersion of germ plasm and nuage
      material in eggs, embryos, PGCs and oocytes in several species of benthic
      (Spadella) and planctonic (Sagitta) chaetognaths. In these animals, germ cells
      and gametes can be observed in vivo throughout the 1-2 month life cycle. After
      describing internal fertilization in live animals we show that the single large
      (15 microm diameter) germ granule forms by a spiralling aggregation movement of
      small germ islands situated in the vegetal cortex at the time of first mitosis.
      We also demonstrate that the granule forms autonomously in unfertilized activated
      eggs or fertilized egg fragments. Once formed, the germ granule first associates
      with the cleavage furrow and is segregated into one of the first two blastomeres.
      The germ granule is then translocated from the cortex to the mitotic spindle
      during 3(rd) cleavage and remains in the single most-vegetal blastomere until the
      32-cell stage. At the 64-cell stage the germ granule is partitioned as nuage
      material into two founder PGCs and further partitioned into four PGCs situated at
      the tip of the archenteron during gastrulation. These four PGCs migrate without
      dividing to reach the transverse septum, then proliferate and differentiate into
      oocytes and spermatocytes of two ovaries and two testes. We noted that germ plasm
      and nuage material were associated with mitochondria, the nucleus, the spindle
      and the centrosome during some stages of development and differentiation of the
      germ line. Finally, we demonstrate that a Vasa-like protein is present in the
      germ granule, in PGCs and in the electron-dense material associated with the
      germinal vesicle of oocytes. These features stress the conservation of cellular
      and molecular mechanisms involved in germ cell determination.

PMID- 11830568
TI  - Requirement of neuropilin 1-mediated Sema3A signals in patterning of the
      sympathetic nervous system.
AB  - Neuropilin 1 is the specific receptor for Sema3A and plays a role in nerve fiber
      guidance. We report that neuropilin 1 and Sema3A mutant mouse embryos, generated
      by targeted gene disruption, showed displacement of sympathetic neurons and their
      precursors and abnormal morphogenesis in the sympathetic trunk. We also show that
      Sema3A suppressed the cell migration activity of sympathetic neurons from wild
      type but not neuropilin 1 mutant embryos in vitro and instead promoted their
      accumulation into compact cell masses and fasciculation of their neurites. These
      findings suggest that the neuropilin 1-mediated Sema3A signals regulate arrest
      and aggregation of sympathetic neuron precursors and sympathetic neurons
      themselves at defined target sites and axon fasciculation to produce the
      stereotyped sympathetic nerve pattern.

PMID- 11830569
TI  - Dual origin of spinal oligodendrocyte progenitors and evidence for the
      cooperative role of Olig2 and Nkx2.2 in the control of oligodendrocyte
      differentiation.
AB  - In this study, we have investigated the relationship of Olig2+ and Nkx2.2+
      oligodendrocyte progenitors (OLPs) by comparing the expression of Olig2 and
      Nkx2.2 in embryonic chicken and mouse spinal cords before and during the stages
      of oligodendrogenesis. At the stages of neurogenesis, Olig2 and Nkx2.2 are
      expressed in adjacent non-overlapping domains of ventral neuroepithelium. During
      oligodendrogenesis stages, these two domains generate distinct populations of
      OLPs. From the Olig2+ motoneuron precursor domain (pMN) arise the Olig2+/Pdgfra+
      OLPs, whereas the Nkx2.2+ p3 domain give rise to Nkx2.2+ OLPs. Despite their
      distinct origins, both populations of OLPs eventually appear to co-express Olig2
      and Nkx2.2 in the same cells. However, there is a species difference in the
      timing of acquiring Nkx2.2 expression by the Olig2+/Pdgfra+ OLPs. The co
      expression of Nkx2.2 and Olig2 in OLPs is tightly associated with myelin gene
      expression in the normal and PDGFA(-/-) embryos, suggesting a cooperative role of
      these transcription factors in the control of oligodendrocyte differentiation. In
      support of this suggestion, inhibition of expression of these two transcription
      factors in culture by antisense oligonucleotides has an additive inhibitory
      effect on OLP differentiation and proteolipid protein (PLP) gene expression.

PMID- 11830570
TI  - Limb type-specific regulation of bric a brac contributes to morphological
      diversity.
AB  - The insect antenna and leg are considered homologous structures, likely to have
      arisen via duplication and divergence from an ancestral limb. Consistent with
      this, the antenna and leg are derived from primordia with similar developmental
      potentials. Nonetheless, the adult structures differ in both form and function.
      In Drosophila, one conspicuous morphological difference is that the antenna has
      fewer distal segments than the leg. We propose that this is due in part to the
      variations in the regulation of bric a brac. bric a brac is required for joint
      formation, and loss of bric a brac function leads to fusion of distal antennal
      and leg segments, resulting in fewer total segments. Here, we address how bric a
      brac is regulated to generate the mature expression patterns of two concentric
      rings in the antenna versus four concentric rings in the leg. We find that bric a
      brac expression is activated early throughout most of the Distal-less domain in
      both antenna and leg and subsequently is restricted to the distal portion and
      into rings. Although bric a brac expression in the antenna and in all four tarsal
      rings of the leg requires Distal-less, only the proximal three tarsal rings are
      Spineless-dependent. Thus bric a brac is regulated differentially even within a
      single appendage type. The restriction of bric a brac expression to the distal
      portion of the Distal-less domain is a consequence of negative regulation by
      distinct sets of genes in different limb types. In the leg, the proximal boundary
      of bric a brac is established by the medial-patterning gene dachshund, but
      dachshund alone is insufficient to repress bric a brac, and the expression of the
      two genes overlaps. In the antenna, the proximal boundary of bric a brac is
      established by an antenna-specifying gene, homothorax, in conjunction with
      dachshund and spalt, and there is much less overlap between the bric a brac and
      the dachshund domains. Thus tissue-specific expression of other patterning genes
      that differentially repress bric a brac accounts for antenna-leg differences in
      bric a brac pattern. We propose that the limb type-specific variations in
      expression of bric a brac repressors contribute to morphological variations by
      controlling distal limb segment number.

PMID- 11830571
TI  - JAK signaling is somatically required for follicle cell differentiation in
      Drosophila.
AB  - Janus kinase (JAK) pathway activity is an integral part of signaling through a
      variety of ligands and receptors in mammals. The extensive re-utilization and
      pleiotropy of this pathway in vertebrate development is conserved in other
      animals as well. In Drosophila melanogaster, JAK signaling has been implicated in
      embryonic pattern formation, sex determination, larval blood cell development,
      wing venation, planar polarity in the eye, and formation of other adult
      structures. Here we describe several roles for JAK signaling in Drosophila
      oogenesis. The gene for a JAK pathway ligand, unpaired, is expressed specifically
      in the polar follicle cells, two pairs of somatic cells at the anterior and
      posterior poles of the developing egg chamber. Consistent with unpaired
      expression, reduced JAK pathway activity results in the fusion of developing egg
      chambers. A primary defect of these chambers is the expansion of the polar cell
      population and concomitant loss of interfollicular stalk cells. These phenotypes
      are enhanced by reduction of unpaired activity, suggesting that Unpaired is a
      necessary ligand for the JAK pathway in oogenesis. Mosaic analysis of both JAK
      pathway transducers, hopscotch and Stat92E, reveals that JAK signaling is
      specifically required in the somatic follicle cells. Moreover, JAK activity is
      also necessary for the initial commitment of epithelial follicle cells. Many of
      these roles are in common with, but distinct from, the known functions of Notch
      signaling in oogenesis. Consistent with these data is a model in which Notch
      signaling determines a pool of cells to be competent to adopt stalk or polar
      fate, while JAK signaling assigns specific identity within that competent pool.

PMID- 11830572
TI  - Micromere lineages in the glossiphoniid leech Helobdella.
AB  - In leech embryos, segmental mesoderm and ectoderm arise from teloblasts by
      lineages that are already relatively well characterized. Here, we present data
      concerning the early divisions and the definitive fate maps of the micromeres, a
      group of 25 small cells that arise during the modified spiral cleavage in leech
      (Helobdella robusta) and contribute to most of the nonsegmental tissues of the
      adult. Three noteworthy results of this work are as follows. (1) The c"' and dm'
      clones (3d and 3c in traditional nomenclature) give rise to a hitherto
      undescribed network of fibers that run from one end of the embryo to the other.
      (2) The clones of micromeres b" and b"' (2b and 3b in traditional nomenclature)
      die in normal development; the b" clone can be rescued to assume the normal c"
      fate if micromere c" or its clone are ablated in early development. (3) Two
      qualitative differences in micromere fates are seen between H. robusta
      (Sacramento) and another Helobdella sp. (Galt). First, in Helobdella sp. (Galt),
      the clone of micromere b" does not normally die, and contributes a subset of the
      cells arising exclusively from c" in H. robusta (Sacramento). Second, in
      Helobdella sp. (Galt), micromere c"' makes no definitive contribution, whereas
      micromere dm' gives rise to cells equivalent to those arising from c"' and dm' in
      H. robusta (Sacramento).

PMID- 11830573
TI  - Elevated transforming growth factor beta2 enhances apoptosis and contributes to
      abnormal outflow tract and aortic sac development in retinoic X receptor alpha
      knockout embryos.
AB  - Septation of the single tubular embryonic outflow tract into two outlet segments
      in the heart requires the precise integration of proliferation, differentiation
      and apoptosis during remodeling. Lack of proper coordination between these
      processes would result in a variety of congenital cardiac defects such as those
      seen in the retinoid X receptor alpha knockout (Rxra(-/-)) mouse. Rxra(-/-)
      embryos exhibit lethality between embryonic day (E) 13.5 and 15.5 and harbor a
      variety of conotruncal and aortic sac defects making it an excellent system to
      investigate the molecular and morphogenic causes of these cardiac malformations.
      At E12.5, before the embryonic lethality, we found no qualitative difference
      between wild type and Rxra(-/-) proliferation (BrdU incorporation) in outflow
      tract cushion tissue but a significant increase in apoptosis as assessed by both
      TUNEL labeling in paraffin sections and caspase activity in trypsin-dispersed
      hearts. Additionally, E12.5 embryos demonstrated elevated levels of transforming
      growth factor beta2 (TGFbeta2) protein in multiple cell lineages in the heart.
      Using a whole-mouse-embryo culture system, wild-type E11.5 embryos treated with
      TGFbeta2 protein for 24 hours displayed enhanced apoptosis in both the
      sinistroventralconal cushion and dextrodorsalconal cushion in a manner analogous
      to that observed in the Rxra(-/-). TGFbeta2 protein treatment also led to
      malformations in both the outflow tract and aortic sac. Importantly, Rxra(-/-)
      embryos that were heterozygous for a null mutation in the Tgfb2 allele exhibited
      a partial restoration of the elevated apoptosis and of the malformations. This
      was evident at both E12.5 and E13.5. The data suggests that elevated levels of
      TGFbeta2 can (1) contribute to abnormal outflow tract morphogenesis by enhancing
      apoptosis in the endocardial cushions and (2) promote aortic sac malformations by
      interfering with the normal development of the aorticopulmonary septum.

PMID- 11830574
TI  - MEX-3 interacting proteins link cell polarity to asymmetric gene expression in
      Caenorhabditis elegans.
AB  - The KH domain protein MEX-3 is central to the temporal and spatial control of PAL
      1 expression in the C. elegans early embryo. PAL-1 is a Caudal-like homeodomain
      protein that is required to specify the fate of posterior blastomeres. While pal
      1 mRNA is present throughout the oocyte and early embryo, PAL-1 protein is
      expressed only in posterior blastomeres, starting at the four-cell stage. To
      better understand how PAL-1 expression is regulated temporally and spatially, we
      have identified MEX-3 interacting proteins (MIPs) and characterized in detail two
      that are required for the patterning of PAL-1 expression. RNA interference of MEX
      6, a CCCH zinc-finger protein, or SPN-4, an RNA recognition motif protein, causes
      PAL-1 to be expressed in all four blastomeres starting at the four-cell stage.
      Genetic analysis of the interactions between these mip genes and the par genes,
      which provide polarity information in the early embryo, defines convergent
      genetic pathways that regulate MEX-3 stability and activity to control the
      spatial pattern of PAL-1 expression. These experiments suggest that par-1 and par
      4 affect distinct processes. par-1 is required for many aspects of embryonic
      polarity, including the restriction of MEX-3 and MEX-6 activity to the anterior
      blastomeres. We find that PAL-1 is not expressed in par-1 mutants, because MEX-3
      and MEX-6 remain active in the posterior blastomeres. The role of par-4 is less
      well understood. Our analysis suggests that par-4 is required to inactivate MEX-3
      at the four-cell stage. Thus, PAL-1 is not expressed in par-4 mutants because MEX
      3 remains active in all blastomeres. We propose that MEX-6 and SPN-4 act with MEX
      3 to translate the temporal and spatial information provided by the early acting
      par genes into the asymmetric expression of the cell fate determinant PAL-1.

PMID- 11830575
TI  - Patterning of the basal telencephalon and hypothalamus is essential for guidance
      of cortical projections.
AB  - We have investigated the mechanisms that control the guidance of corticofugal
      projections as they extend along different subdivisions of the forebrain. To this
      aim, we analyzed the development of cortical projections in mice that lack Nkx2
      1, a homeobox gene whose expression is restricted to two domains within the
      forebrain: the basal telencephalon and the hypothalamus. Molecular
      respecification of the basal telencephalon and hypothalamus in Nkx2-1-deficient
      mice causes a severe defect in the guidance of layer 5 cortical projections and
      ascending fibers of the cerebral peduncle. These axon tracts take an abnormal
      path when coursing through both the basal telencephalon and hypothalamus. By
      contrast, loss of Nkx2-1 function does not impair guidance of corticothalamic or
      thalamocortical axons. In vitro experiments demonstrate that the basal
      telencephalon and the hypothalamus contain an activity that repels the growth of
      cortical axons, suggesting that loss of this activity is the cause of the defects
      observed in Nkx2-1 mutants. Furthermore, analysis of the expression of candidate
      molecules in the basal telencephalon and hypothalamus of Nkx2-1 mutants suggests
      that Slit2 contributes to this activity.

PMID- 11830576
TI  - Endoderm is required for vascular endothelial tube formation, but not for
      angioblast specification.
AB  - Angioblasts, the precursor cells that comprise the endothelial layer of blood
      vessels, arise from a purely mesodermal population. Individual angioblasts
      coalesce to form the primary vascular plexus through a process called
      vasculogenesis. A number of reports in the literature suggest that signals from
      the adjacent endoderm are necessary to induce angioblast specification within the
      mesoderm. We present evidence, using both embryological and molecular techniques,
      indicating that endoderm is not necessary for the induction of angioblasts.
      Xenopus embryos that had endoderm physically removed at the onset of gastrulation
      still express vascular markers. Furthermore, animal caps stimulated with bFGF
      form angioblasts in the absence of any detectable endodermal markers. These
      results show that endoderm is not required for the initial formation of
      angioblasts. While Xenopus embryos lacking endoderm contain aggregates of
      angioblasts, these angioblasts fail to assemble into endothelial tubes.
      Endothelial tube formation can be rescued, however, by implantation of endodermal
      tissue from sibling embryos. Based on these studies in Xenopus, and corroborating
      experiments using the quail embryo, we conclude that endoderm is not required for
      angioblast specification, but does play an essential role in the formation of
      vascular tubes.

PMID- 11830577
TI  - A hypomorphic allele of dab1 reveals regional differences in reelin-Dab1
      signaling during brain development.
AB  - The disabled 1 (Dab1) p80 protein is essential for reelin signaling during brain
      development. p80 has an N-terminal domain for association with reelin receptors,
      followed by reelin-dependent tyrosine phosphorylation sites and about 310 C
      terminal residues of unknown function. We have generated mutant mice that express
      only a natural splice form of Dab1, p45, that lacks the C-terminal region of p80.
      The normal development of these mice implies that the receptor-binding region and
      tyrosine phosphorylation sites of p80 are sufficient for reelin signaling.
      However, a single copy of the truncated gene does not support normal development
      of the neocortex and hippocampus. The CA1 region of the hippocampus is split into
      two well-organized layers, while the marginal zone of the neocortex is invaded by
      late-born cortical plate neurons. The haploinsufficiency of the p45 allele of
      Dab1 implies that the C terminus of p80 affects the strength of reelin-Dab1
      signaling, yet there is no apparent change in reelin-dependent tyrosine
      phosphorylation of p45 relative to p80. Therefore, we suggest that the C-terminal
      region of Dab1 p80 is involved in signaling to downstream effector molecules.
      Furthermore, the presence of late-born cortical plate neurons in the marginal
      zone reveals a requirement for reelin-Dab1 signaling in late-born cortical plate
      neurons, and helps distinguish models for the cortical inversion in the reeler
      mutant mouse.

PMID- 11830578
TI  - The homeodomain protein Vax2 patterns the dorsoventral and nasotemporal axes of
      the eye.
AB  - The vertebrate retina is highly ordered along both its dorsoventral (DV) and
      nasotemporal (NT) axes, and this order is topographically maintained in its
      axonal connections to the superior colliculus of the midbrain. Although the
      graded axon guidance cues that mediate the topographic mapping of
      retinocollicular connections are increasingly well understood, the
      transcriptional regulators that set the DV and NT gradients of these cues are
      not. We now provide genetic evidence that Vax2, a homeodomain protein expressed
      in the ventral retina, is one such regulator. We demonstrate that in Vax2 mutant
      mice, retinocollicular projections from the ventral temporal retina are
      dorsalized relative to wild type. Remarkably, however, this dorsalization becomes
      systematically less severe in progressively more nasal regions of the ventral
      retina. Vax2 mutants also exhibit flattened DV and NT gradients of the EphA5,
      EphB2, EphB3, ephrin-B1 and ephrin-B2 axon guidance cues. Together, these data
      identify Vax2 as a fundamental regulator of axial polarization in the mammalian
      retina.

PMID- 11830579
TI  - Vax2 inactivation in mouse determines alteration of the eye dorsal-ventral axis,
      misrouting of the optic fibres and eye coloboma.
AB  - Vax2 is a homeobox gene whose expression is confined to the ventral region of the
      prospective neural retina. Overexpression of this gene at early stages of
      development in Xenopus and in chicken embryos determines a ventralisation of the
      retina, thus suggesting its role in the molecular pathway that underlies eye
      development. We describe the generation and characterisation of a mouse with a
      targeted null mutation of the Vax2 gene. Vax2 homozygous mutant mice display
      incomplete closure of the optic fissure that leads to eye coloboma. This
      phenotype is not fully penetrant, suggesting that additional factors contribute
      to its generation. Vax2 inactivation determines dorsalisation of the expression
      of mid-late (Ephb2 and Efnb2) but not early (Pax2 and Tbx5) markers of dorsal
      ventral polarity in the developing retina. Finally, Vax2 mutant mice exhibit
      abnormal projections of ventral retinal ganglion cells. In particular, we
      observed the almost complete absence of ipsilaterally projecting retinal ganglion
      cells axons in the optic chiasm and alteration of the retinocollicular
      projections. All these findings indicate that Vax2 is required for the proper
      closure of the optic fissure, for the establishment of a physiological asymmetry
      on the dorsal-ventral axis of the eye and for the formation of appropriate
      retinocollicular connections.

PMID- 11830580
TI  - Localization of microsomal triglyceride transfer protein in the Golgi: possible
      role in the assembly of chylomicrons.
AB  - Although a critical role of microsomal transfer protein (MTP) has been recognized
      in the assembly of nascent apolipoprotein B (apoB)-containing lipoproteins, it
      remains unclear where and how MTP transfers lipids in the secretory pathway
      during the maturational process of apoB lipidation. The aims of this study were
      to determine whether MTP functions in the secretory pathway as well as in the
      endoplasmic reticulum and whether its large 97-kDa subunit interacts with the
      small 58-kDa protein disulfide isomerase (PDI) subunit and apoB, particularly in
      the Golgi apparatus. Using a high resolution immunogold approach combined with
      specific polyclonal antibodies, the large and small subunits of MTP were observed
      over the rough endoplasmic reticulum and the Golgi. Double immunocytochemical
      detection unraveled the colocalization of MTP and PDI as well as MTP and apoB in
      these same subcellular compartments. To confirm the spatial contact of these
      proteins, Golgi fractions were isolated, homogenized, and incubated with an anti
      MTP large subunit antibody. Immunoprecipitates were applied on SDS-PAGE and then
      transferred on to nitrocellulose. Immunoblotting the membrane with PDI and apoB
      antibodies confirmed the colocalization of these proteins with MTP. Furthermore,
      MTP activity assay disclosed a substantial triglyceride transfer in the Golgi
      fractions. The occurrence of membrane-associated apoB in the Golgi, coupled with
      its interaction with active MTP, suggests an important role for the Golgi in the
      biogenesis of apoB-containing lipoproteins.

PMID- 11830581
TI  - Identification and characterization of prolylcarboxypeptidase as an endothelial
      cell prekallikrein activator.
AB  - Our recent investigations have postulated a human umbilical vein endothelial cell
      (HUVEC)-associated prekallikrein activator (PKA). When prekallikrein (PK)
      assembles on high molecular weight kininogen on HUVEC, PK is activated to
      kallikrein. PKA was found in the 15,800 x g pellet of HUVEC lysates using an
      assay that measures PK activation only when bound to high molecular weight
      kininogen linked to microtiter plates. Sequential DEAE, wheat germ lectin
      affinity, and hydroxyapatite chromatography resulted in four protein bands on SDS
      PAGE. One protein in the 73-kDa band was identified by amino acid sequencing as
      prolylcarboxypeptidase (PRCP). On gel filtration, PKA activity was a single
      homogenous peak identical in migration to the 73-kDa immunoblot of PRCP. Anti
      PRCP inhibits PKA activity and PK activation on HUVEC. Purified PKA was blocked
      by diisopropyl fluorophosphate (1 mm), phenylmethylsulfonyl fluoride (3 mm),
      leupeptin (100 microm), antipain (IC(50) = 2 microm), HgCl(2) (IC(50) = 500
      microm), Z-Pro-Pro-aldehyde-dimethyl acetate (IC(50) = 1 microm), and corn
      trypsin inhibitor (IC(50) = 40 nm). PKA did not correct the coagulant defect in
      factor XII deficient plasma, was purified from HUVEC cultured in factor XII
      deficient serum, was not detected by antibody to factor XII, did not activate
      FXI, and was not inhibited by a neutralizing antibody to FXII. Angiotensin II
      (IC(50) = 2 microm) or bradykinin (IC(50) = 100 microm), but not angiotensin II
      (1-7) or bradykinin(1-5), and the prolyl oligopeptidase inhibitor Fmoc-Ala-Pyr-CN
      (IC(50) = 50 nm) also blocked purified PKA activation of PK. The K(m) of PK
      activation by PRCP is 6.7 nm. PRCP antigen is present on the membrane of fixed
      but not permeabilized HUVEC. PRCP appears to be a HUVEC-associated PK activator.

PMID- 11830582
TI  - Structure-function analysis of NADE: identification of regions that mediate nerve
      growth factor-induced apoptosis.
AB  - Nerve growth factor (NGF) can induce apoptosis in neural cells via activation of
      the low affinity neurotrophin receptor p75NTR. NADE (p75NTR-associated cell death
      executor) is a p75NTR-associated protein that mediates apoptosis in response to
      NGF by interacting with the death domain of p75NTR in 293T, PC12, and nnr5 cells
      (Mukai, J., Hachiya, T., Shoji-Hoshino, S., Kimura, M. T., Nadano, D., Suvanto,
      P., Hanaoka, T., Li, Y., Irie, S., Greene, L. A., and Sato, T. A. (2000) J. Biol.
      Chem. 275, 17566-17570). We performed extensive mutational analysis on NADE, to
      better characterize its structural and functional features. Truncation of a
      minimal region, including amino acid residues 41-71 of NADE, was found to be
      sufficient to induce apoptosis. The designated regulatory region includes the C
      terminal amino acid residues (72-112) and is essential for NGF-dependent
      regulation of NADE-induced apoptosis. Furthermore, the mutants with amino acid
      substitutions in the leucine-rich nuclear export signal (NES) sequence (residues
      90-100) abolished the export of NADE from the nucleus to the cytoplasm. Mutation
      of the NES also abolished self-association of NADE, its interaction with p75NTR,
      and NGF-dependent apoptosis. Expression of a fragment of NADE (amino acid
      residues 81-124) blocked NGF-induced apoptosis in oligodendrocytes, suggesting
      that this region has a dominant negative effect on NGF/p75NTR-induced apoptosis.
      These studies identify distinct regions of NADE that are involved in regulating
      specific functions involved in p75NTR signal transduction.

PMID- 11830583
TI  - Identification of a soluble form phospholipase A2 receptor as a circulating
      endogenous inhibitor for secretory phospholipase A2.
AB  - Venomous snakes have various types of phospholipase A(2) inhibitory proteins
      (PLIs) in their circulatory system to protect them from attack by their own
      phospholipase A(2)s (PLA(2)s). Here we show the first evidence for the existence
      of circulating PLI against secretory PLA(2)s (sPLA(2)s) in mammals. In mouse
      serum, we detected specific binding activities of group IB and X sPLA(2)s, which
      was in contrast with the absence of binding activities in serum prepared from
      mice deficient in PLA(2) receptor (PLA(2)R), a type I transmembrane glycoprotein
      related to the C-type animal lectin family. Western blot analysis after partial
      purification with group IB sPLA(2) affinity column confirmed the identity of
      serum sPLA(2)-binding protein as a soluble form of PLA(2)R (sPLA(2)R) that
      retained all of the extracellular domains of the membrane-bound receptor. Both
      purified sPLA(2)R and the recombinant soluble receptor having all of the
      extracellular portions blocked the biological functions of group X sPLA(2),
      including its potent enzymatic activity and its binding to the membrane-bound
      receptor. Protease inhibitor tests with PLA(2)R-overexpressing Chinese hamster
      ovary cells suggested that sPLA(2)R is produced by cleavage of the membrane-bound
      receptor by metalloproteinases. Thus, sPLA(2)R is the first example of
      circulating PLI that acts as an endogenous inhibitor for enzymatic activities and
      receptor-mediated functions of sPLA(2)s in mice.

PMID- 11830584
TI  - The up-regulation of stromelysin-1 (MMP-3) in a spontaneously demyelinating
      transgenic mouse precedes onset of disease.
AB  - The matrix metalloproteinases (MMPs) are a family of endoproteinases that degrade
      various components of the extracellular matrix and have been implicated in the
      pathogenesis of multiple sclerosis. To determine whether up-regulation of MMP-3,
      or stromelysin-1, was a causative factor during the development of demyelination,
      we have examined the expression of MMP-3 mRNA and protein in brain tissue of a
      spontaneously demyelinating mouse model overexpressing DM20 (ND4 line) prior to
      and during the progression of disease. Stromelysin-1, but not other MMP mRNA was
      elevated approximately 10-fold in transgenic mice between 5 days and 1 month of
      age, more than 2 months before the onset of disease, and was coordinately
      expressed with the DM20 transgene. Stromelysin-1 protein levels were also up
      regulated as was tissue inhibitor of metalloproteinase-1 (TIMP-1), an in vivo
      regulator of stromelysin-1 mRNA. When we crossed our ND4 mice with a line of
      transgenic mice overexpressing TIMP-1 in brain, clinical signs in these mice were
      attenuated, and the level of stromelysin-1 protein was reduced. Thus, in this
      transgenic model of demyelinating disease up-regulation of DM20, MMP-3, and TIMP
      1 represent important changes in the chemical pathogenesis in brain, which
      precede the onset of disease.

PMID- 11830585
TI  - Bacterial peptidoglycan-associated lipoprotein is released into the bloodstream
      in gram-negative sepsis and causes inflammation and death in mice.
AB  - Gram-negative bacterial sepsis commonly causes organ dysfunction and death in
      humans. Although circulating bacterial toxins trigger inflammation in sepsis,
      little is known about the composition of bacterial products released into the
      blood during sepsis or the contribution of various bacterial components to the
      pathogenesis of sepsis. We have shown that diverse Gram-negative bacteria release
      bacterial peptidoglycan-associated lipoprotein (PAL) into serum. The present
      studies explored release of PAL into the blood during sepsis and tested the
      hypothesis that PAL contributes to bacterial virulence and inflammation in Gram
      negative sepsis. Released PAL was detected in the blood of 94% of mice following
      cecal ligation and puncture. Picomolar to nanomolar levels of PAL stimulated
      macrophages and splenocytes from lipopolysaccharide-hyporesponsive (C3H/HeJ)
      mice. Injection of PAL into C3H/HeJ mice stimulated production of serum cytokines
      and increased pulmonary and myocardial expression of inflammatory markers. PAL
      caused death in sensitized C3H/HeJ mice. Mutant Escherichia coli bacteria with
      reduced levels of PAL or truncated PAL were less virulent than wild-type
      bacteria, as indicated by higher survival rates and lower circulating levels of
      interleukin 6 and bacteria in a model of peritonitis in lipopolysaccharide
      responsive mice. The studies suggest that PAL may be an important bacterial
      mediator of Gram-negative sepsis.

PMID- 11830586
TI  - Mutations that destabilize the gp41 core are determinants for stabilizing the
      simian immunodeficiency virus-CPmac envelope glycoprotein complex.
AB  - The human and simian immunodeficiency viruses (HIV and SIV) envelope glycoprotein
      consists of a trimer of two noncovalently and weakly associated subunits, gp120
      and gp41. Upon binding of gp120 to cellular receptors, this labile native
      envelope complex undergoes conformational changes, resulting in a stable trimer
      of-hairpins structure in gp41. Formation of the hairpin structure is thought to
      mediate membrane fusion by placing the viral and cellular membranes in close
      proximity. An in vitro-derived variant of SIVmac251, denoted CPmac, has acquired
      an unusually stable virion-associated gp120-gp41 complex. This unique phenotype
      is conferred by five amino acid substitutions in the gp41 ectodomain. Here we
      characterize the structural and physicochemical properties of the N40(L6)C38
      model of the CPmac gp41 core. The 1.7-A resolution crystal structure of
      N40(L6)C38 is very similar to the six-helix bundle structure present in the
      parent SIVmac251 gp41. In both structures, three N40 peptides form a central
      three-stranded coiled coil, and three C38 peptides pack in an antiparallel
      orientation into hydrophobic grooves on the coiled-coil surface. Thermal
      unfolding studies show that the CPmac mutations destabilize the SIVmac251 six
      helix bundle by 15 kJ/mol. Our results suggest that the formation of the gp41
      trimer-of-hairpins structure is thermodynamically coupled to the conformational
      stability of the native envelope glycoprotein and raise the intriguing
      possibility that introduction of mutations to destabilize the six-helix bundle
      may lead to the stabilization of the trimeric gp120-gp41 complex. This study
      suggests a potential strategy for the production of stably folded envelope
      protein immunogens for HIV vaccine development.

PMID- 11830587
TI  - The human herpes virus 8-encoded viral FLICE inhibitory protein physically
      associates with and persistently activates the Ikappa B kinase complex.
AB  - The human herpesvirus 8 (HHV8, also called Kaposi's sarcoma-associated
      herpesvirus) has been linked to Kaposi's sarcoma and primary effusion lymphoma
      (PEL) in immunocompromised individuals. We demonstrate that PEL cell lines have a
      constitutively active NF-kappaB pathway, which is associated with persistent
      phosphorylation of IkappaBalpha. To elucidate the mechanism of NF-kappaB
      activation in PEL cell lines, we have investigated the role of viral FLICE
      inhibitory protein (vFLIP) in this process. We report that stable expression of
      HHV8 vFLIP in a variety of cell lines is associated with persistent NF-kappaB
      activation caused by constitutive phosphorylation of IkappaBalpha. HHV8 vFLIP
      gets recruited to a approximately 700-kDa IkappaB kinase (IKK) complex and
      physically associates with IKKalpha, IKKbeta, NEMO/IKKgamma, and RIP. HHV8 vFLIP
      is incapable of activating NF-kappaB in cells deficient in NEMO/IKKgamma, thereby
      suggesting an essential role of an intact IKK complex in this process. Our
      results suggest that HHV8 vFLIP might contribute to the persistent NF-kappaB
      activation observed in PEL cells by associating with and stimulating the activity
      of the cellular IKK complex.

PMID- 11830589
TI  - Low-density lipoprotein receptor-related protein mediates the endocytosis of
      anionic liposomes in neurons.
AB  - We have recently demonstrated that anionic liposomes efficiently introduce
      foreign DNA into postmitotic neurons and other cell types (Lakkaraju, A.,
      Dubinsky, J. M., Low, W. C., and Rahman, Y.-E. (2001) J. Biol. Chem. 276, 32000
      32007). To investigate the mechanism of liposome uptake, we followed the
      internalization of anionic liposome-encapsulated Cy3-labeled oligonucleotides (AL
      Cy3ONs) by hippocampal neurons using confocal microscopy. Uptake of AL-Cy3ONs was
      widespread and time- and temperature-dependent, indicative of receptor-mediated
      endocytosis. The low-density lipoprotein receptor-related protein (LRP) was
      crucial for anionic liposome endocytosis because the receptor-associated protein
      or an anti-LRP antibody inhibited internalization, and fibroblasts lacking LRP
      did not internalize AL-Cy3ONs. Using selective endocytosis inhibitors, we found
      that liposome endocytosis and intracellular transport required clathrin, dynamin,
      an intact cytoskeletal network, and phosphatidylinositol 3-kinase activity.
      Cy3ONs did not significantly colocalize with recycling endosomal/lysosomal
      markers and entered neuronal nuclei within 1-3 h of incubation. Approximately 50%
      of the internalized liposomal phospholipids were recycled back to the cell
      surface, in keeping with the fluidity of their acyl chains. Liposome endocytosis
      did not require heparan sulfate proteoglycans or cause calcium influx into
      neurons. Thus, constitutive endocytosis of anionic liposomes by LRP utilizes only
      one component, in contrast to the more involved heparan sulfate proteoglycan-LRP
      pathway implicated in the pathogenesis of Alzheimer's disease.

PMID- 11830588
TI  - The role of endogenous human Trp4 in regulating carbachol-induced calcium
      oscillations in HEK-293 cells.
AB  - We utilized 2-aminoethyoxydiphenyl borane, an agent that blocks store-operated
      Ca(2+) entry, as well as an antisense approach to characterize endogenous Ca(2+)
      entry pathways in HEK-293 cells. The thapsigargin- and carbachol-induced, but not
      the 1-oleolyl-2-acytyl-sn-glycerol (OAG)-induced, entry was blocked by 2
      aminoethyoxydiphenyl borane. Both reverse transcriptase-PCR and Western blot
      analyses demonstrated endogenous expression for HTRP1, HTRP3, and HTRP4 and
      specific suppression of mRNA levels and Trp protein levels in cells stably
      expressing antisense constructs. Expression of HTRP4 antisense inhibited 35% of
      the carbachol (CCh)-stimulated Ba(2+) entry and 46% of the OAG-stimulated Sr(2+)
      entry but in contrast had no effect on the thapsigargin-stimulated Ba(2+) or
      Sr(2+) entry. HTRP3 antisense reduced, while HTRP1 antisense had no effect on,
      OAG-induced Sr(2+) entry. Of greater importance, HTRP4 antisense expression, but
      not HTRP3 antisense expression, blocked the sustained Ca(2+) oscillations
      produced by low doses of CCh (15 microm), arguing that receptor-stimulated rather
      than store-operated channels are involved in these sustained oscillations. HTRP4
      antisense also inhibited 75% of the arachidonic acid-induced Ca(2+) entry. In
      summary, these data suggest that HTRP4 proteins in HEK-293 cells, differing from
      HTRP3 and HTRP1 proteins, do not serve as functional subunits of store-operated
      channels but do function as subunits for CCh- and OAG-stimulated channels.
      Furthermore, evidence is provided for the first time for the involvement of a Trp
      isoform (HTRP4) in the formation of the channel responsible for both arachidonic
      acid-induced Ca(2+) entry and the Ca(2+) entry needed to sustain long term Ca(2+)
      oscillations induced by low doses of carbachol.

PMID- 11830590
TI  - Critical role of tumor necrosis factor-alpha and NF-kappa B in interferon-gamma 
      induced CD40 expression in microglia/macrophages.
AB  - CD40 is a member of the tumor necrosis factor (TNF) receptor superfamily. CD40
      expression on antigen-presenting cells (including macrophages and microglia) is
      crucial for T-cell activation. Aberrant expression of CD40 has been associated
      with autoimmune inflammatory diseases such as multiple sclerosis and rheumatoid
      arthritis. We have recently shown that the cytokine interferon (IFN)-gamma is the
      most potent inducer of CD40 expression in macrophages and microglia, and this
      induction is mediated by the IFN-gamma-activated transcription factor STAT-1alpha
      and constitutively expressed PU.1 and/or Spi-B. In this study, we have discovered
      that a major component of IFN-gamma-induced CD40 expression involves the
      endogenous production of the cytokine TNF-alpha. The inclusion of anti-TNF-alpha
      neutralizing antibody significantly inhibits IFN-gamma-induced CD40 mRNA and CD40
      promoter activity. IFN-gamma-induced CD40 protein expression is attenuated in TNF
      alpha-deficient microglia and can be restored with exogenous TNF-alpha. Site
      directed mutagenesis studies demonstrate that three of the four NF-kappaB
      elements in the CD40 promoter are required for IFN-gamma-induced CD40 promoter
      activity. IFN-gamma treatment leads to the activation of NF-kappaB in a time
      dependent manner, which is inhibited in the presence of anti-TNF-alpha
      neutralizing antibody. These results indicate that IFN-gamma-induced TNF-alpha
      production and subsequent NF-kappaB activation are integral parts of the
      mechanism of IFN-gamma-induced CD40 expression.

PMID- 11830591
TI  - Regulation of histone acetylation and transcription by nuclear protein pp32, a
      subunit of the INHAT complex.
AB  - Histone acetylation by p300/CBP and PCAF coactivators is considered to be a key
      mechanism of chromatin modification and transcriptional regulation. A
      multiprotein cellular complex, INHAT (inhibitor of acetyltransferases),
      containing the Set/TAF-Ibeta oncoprotein and pp32 strongly inhibits the HAT
      activity of p300/CBP and PCAF by histone masking. Here we report that the INHAT
      complex and its subunits have overlapping but distinct HAT inhibitory and histone
      binding characteristics. We provide evidence suggesting that the histone binding
      and INHAT activity of pp32 can be regulated by its physical association with
      other INHAT subunits. In vivo colocalization and transfection studies show that
      pp32 INHAT domains are responsible for histone binding, HAT inhibitory activity,
      and repression of transcription. We propose that INHAT and its subunits may
      function by modulating histone acetyltransferases through a histone-masking
      mechanism and may play important regulatory roles in the establishment and
      maintenance of the newly proposed "histone code" of chromatin.

PMID- 11830592
TI  - Pax3 down-regulation and shut-off of melanogenesis in melanoma B16/F10.9 by
      interleukin-6 receptor signaling.
AB  - The microphthalmia-associated transcription factor (Mitf) is essential for
      melanocytic lineage development and for expression of melanogenic enzymes, such
      as tyrosinase. Interleukin-6 receptor/interleukin-6 chimera (IL6RIL6) induces in
      B16/F10.9 melanoma cells a loss of melanogenesis preceded by a sharp decrease in
      Mitf mRNA and gene promoter activity. In the Mitf promoter, the main cis-acting
      element mediating the IL6RIL6 effect is shown to be the binding site of Pax3, a
      paired homeodomain factor regulating among other things the development of
      melanocytes. Pax3 protein and mRNA levels decline steadily after IL6RIL6
      treatment, and overexpression of an ectopic Pax3 cDNA suppresses the Mitf
      promoter inhibition. Loss of the synergism between Pax3 and Sox10, a high
      mobility group domain costimulatory factor, seems to be critical in the rapid
      decrease in Mitf gene expression. The Pax3 down-regulation in IL6RIL6-induced
      F10.9 cell is linked to growth arrest and transdifferentiation to a glial cell
      phenotype. IL6RIL6 stimulates the interleukin-6 family cytokine receptor gp130,
      leading to the rapid phosphorylation of Stat3 on tyrosine 705. This
      phosphorylation is required for Pax3 down-regulation and Mitf promoter silencing
      since these are inhibited in F10.9 cells overexpressing the Stat3 DN-mutant
      Y705F.

PMID- 11830593
TI  - Duplicated binding sites for (1-->3)-beta-D-glucan in the horseshoe crab
      coagulation factor G: implications for a molecular basis of the pattern
      recognition in innate immunity.
AB  - The horseshoe crab factor G, a heterodimeric serine protease zymogen, is
      activated by (1-->3)-beta-D-glucan on fungal cell walls. The activation initiates
      the hemolymph-clotting cascade, a critical reaction for the defense against
      microorganisms. In the present study, we identified the domain responsible for
      the glucan recognition by factor G and characterized its interaction with (1-->3)
      beta-d-glucan and its derivatives. Among three domains in subunit alpha of factor
      G, identified as the glucan-binding domain, was the COOH-terminal xylanase Z-like
      domain composed of two tandem-repeating units, each of which exhibits sequence
      similarities to the cellulose-binding domains of bacterial xylanases. Each of the
      single units bound to the glucan with lower affinities, and the association
      constant increased two orders with the tandem-repeating structure (K(a) = 8.0 x
      10(8) m(-1)). In addition to longer glucans, (1-->3)-beta-D-glucan
      oligosaccharides incapable of activating factor G bound also to factor G and
      competitively inhibited the zymogen activation. The minimum structure required
      for the binding was a (1-->3)-beta-d-glucan disaccharide, indicating that
      conformation-dependent structures are not essential for the recognition.
      Therefore, increasing avidity by multivalent binding sites with low affinities to
      simple structures on biologically active polymers may be one of the principles
      that allows stable and specific recognition of pathogens by pattern recognition
      receptors in innate immunity.

PMID- 11830594
TI  - An Escherichia coli mutant lacking the cold shock-induced palmitoleoyltransferase
      of lipid A biosynthesis: absence of unsaturated acyl chains and antibiotic
      hypersensitivity at 12 degrees C.
AB  - An acyltransferase induced by cold shock in Escherichia coli, designated LpxP,
      incorporates a palmitoleoyl moiety into nascent lipid A in place of the secondary
      laurate chain normally added by LpxL(HtrB) (Carty, S. M., Sreekumar, K. R., and
      Raetz, C. R. H. (1999) J. Biol. Chem. 274, 9677-9685). To determine whether the
      palmitoleoyl residue alters the properties of the outer membrane and imparts
      physiological benefits at low growth temperatures, we constructed a chromosomal
      insertion mutation in lpxP, the structural gene for the transferase. Membranes
      from the lpxP mutant MKV11 grown at 12 degrees C lacked the cold-induced
      palmitoleoyltransferase present in membranes of cold-shocked wild type cells but
      retained normal levels of the constitutive lauroyltransferase encoded by lpxL.
      When examined by mass spectrometry, about two-thirds of the lipid A molecules
      isolated from wild type E. coli grown at 12 degrees C contained palmitoleate in
      place of laurate, whereas the lipid A of cold-adapted MKV11 contained only
      laurate in amounts comparable with those seen in wild type cells grown at 30
      degrees C or above. To probe the integrity of the outer membrane, MKV11 and an
      isogenic wild type strain were grown at 30 or 12 degrees C and then tested for
      their susceptibility to antibiotics. MKV11 exhibited a 10-fold increase in
      sensitivity to rifampicin and vancomycin at 12 degrees C compared with wild type
      cells but showed identical resistance when grown at 30 degrees C. We suggest that
      the palmitoleoyltransferase may confer a selective advantage upon E. coli cells
      growing at lower temperatures by making the outer membrane a more effective
      barrier to harmful chemicals.

PMID- 11830595
TI  - A triple mutant of Escherichia coli lacking secondary acyl chains on lipid A.
AB  - All possible combinations of insertion mutations in the three genes encoding the
      acyl carrier protein-dependent late acyltransferases of lipid A biosynthesis,
      designated lpxL(htrB), lpxM(msbB), and lpxP, were generated in Escherichia coli
      K12 W3110. Mutants defective in lpxM synthesize penta-acylated lipid A molecules
      and grow normally. Strains lacking lpxP fail to incorporate palmitoleate into
      their lipid A at 12 degrees C but make normal amounts of hexa-acylated lipid A
      and are viable. Although lpxL mutants and lpxL lpxM double mutants grow slowly on
      minimal medium at all temperatures, they do not grow on nutrient broth above 32
      degrees C. Such mutants retain the ability to synthesize some penta- and hexa
      acylated lipid A molecules because of limited induction of lpxP at 30 degrees C
      but not above 32 degrees C. MKV15, an E. coli lpxL lpxM lpxP triple mutant,
      likewise grows slowly on minimal medium at all temperatures but not on nutrient
      broth at any temperature. MKV15 synthesizes a lipid A molecule containing only
      the four primary (R)-3-hydroxymyristoyl chains. The outer membrane localization
      and content of lipid A are nearly normal in MKV15, as is the glycerophospholipid
      and membrane protein composition. However, the rate at which the tetra-acylated
      lipid A of MKV15 is exported to the outer membrane is reduced compared with wild
      type. The integrity of the outer membrane of MKV15 is compromised, as judged by
      antibiotic hypersensitivity, and MKV15 undergoes lysis following centrifugation.
      MKV15 may prove useful as a host strain for expressing late acyltransferase genes
      from other Gram-negative bacteria, facilitating the re-engineering of lipid A
      structure in living cells and the design of novel vaccines.

PMID- 11830596
TI  - Remarkable stability of solubilized and delipidated sarcoplasmic reticulum Ca2+
      ATPase with tightly bound fluoride and magnesium against detergent-induced
      denaturation.
AB  - Conditions were developed in the absence of Ca(2+) for purification,
      delipidation, and long term stabilization of octaethylene glycol monododecyl
      ether (C(12)E(8))-solubilized sarcoplasmic reticulum Ca(2+)-ATPase with tightly
      bound Mg(2+) and F(-), an analog for the phosphoenzyme intermediate without bound
      Ca(2+). The Ca(2+)-ATPase activity to monitor denaturation was assessed after
      treatment with 20 mm Ca(2+) to release tightly bound Mg(2+)/F(-). The
      purification and delipidation was successfully achieved with Reactive Red-agarose
      affinity chromatography. The solubilized Mg(2+)/F(-)-bound Ca(2+)-ATPase was very
      rapidly denatured at pH 8, but was perfectly stabilized at pH 6 against
      denaturation for over 20 days at 4 degrees C even without exogenously added
      phospholipid and at a high C(12)E(8)/enzyme weight ratio (10:1). The activity was
      not restored unless the enzyme was treated with 20 mm Ca(2+), showing that
      tightly bound Mg(2+)/F(-) was not released during the long term incubation. The
      perfect stability was attained with or without 0.1 mm dithiothreitol, but
      inactivation occurred with a half-life of 10 days in the presence of 1 mm
      dithiothreitol, possibly due to reduction of a specific disulfide bond(s). The
      remarkable stability is likely conferred by intimate gathering of cytoplasmic
      domains of Ca(2+)-ATPase molecule induced by tight binding of Mg(2+)/F(-). The
      present study thus reveals an essential property of the Mg(2+)/F(-)/Ca(2+)-ATPase
      complex, which will likely provide clues to understanding structure of the Ca(2+)
      released form of phosphoenzyme intermediate at an atomic level.

PMID- 11830597
TI  - RhoA sustains integrin alpha IIbbeta 3 adhesion contacts under high shear.
AB  - The small GTPase RhoA modulates the adhesive nature of many cell types; however,
      despite high levels of expression in platelets, there is currently limited
      evidence for an important role for this small GTPase in regulating platelet
      adhesion processes. In this study, we have examined the role of RhoA in
      regulating the adhesive function of the major platelet integrin,
      alpha(IIb)beta(3). Our studies demonstrate that activation of RhoA occurs as a
      general feature of platelet activation in response to soluble agonists (thrombin,
      ADP, collagen), immobilized matrices (von Willebrand factor (vWf), fibrinogen)
      and high shear stress. Blocking the ligand binding function of integrin
      alpha(IIb)beta(3), by pretreating platelets with c7E3 Fab, demonstrated the
      existence of integrin alpha(IIb)beta(3)-dependent and -independent mechanisms
      regulating RhoA activation. Inhibition of RhoA (C3 exoenzyme) or its downstream
      effector Rho kinase had no effect on integrin alpha(IIb)beta(3) activation
      induced by soluble agonists or adhesive substrates, however, both inhibitors
      reduced shear-dependent platelet adhesion on immobilized vWf and shear-induced
      platelet aggregation in suspension. Detailed analysis of the sequential adhesive
      steps required for stable platelet adhesion on a vWf matrix under shear
      conditions revealed that RhoA did not regulate platelet tethering to vWf or the
      initial formation of integrin alpha(IIb)beta(3) adhesion contacts but played a
      major role in sustaining stable platelet-matrix interactions. These studies
      define a critical role for RhoA in regulating the stability of integrin
      alpha(IIb)beta(3) adhesion contacts under conditions of high shear stress.

PMID- 11830598
TI  - Identification of coenzyme M biosynthetic phosphosulfolactate synthase: a new
      family of sulfonate-biosynthesizing enzymes.
AB  - The hyperthermophilic euryarchaeon Methanococcus jannaschii uses coenzyme M (2
      mercaptoethanesulfonic acid) as the terminal methyl carrier in methanogenesis. We
      describe an enzyme from that organism, (2R)-phospho-3-sulfolactate synthase
      (ComA), that catalyzes the first step in coenzyme M biosynthesis. ComA catalyzed
      the stereospecific Michael addition of sulfite to phosphoenolpyruvate over a
      broad range of temperature and pH conditions. Substrate and product analogs
      moderately inhibited activity. This enzyme has no significant sequence similarity
      to previously characterized enzymes; however, its Mg(2+)-dependent enzyme
      reaction mechanism may be analogous to one proposed for enolase. A diverse group
      of microbes and plants have homologs of ComA that could have been recruited for
      sulfolactate or sulfolipid biosyntheses.

PMID- 11830599
TI  - Screening trials are even more difficult than we thought they were.

PMID- 11830600
TI  - Consortium piecing together role of ATM gene in breast cancer.

PMID- 11830601
TI  - New cigarette advertisements reignite debate on safety.

PMID- 11830603
TI  - 'Light' cigarettes offer no benefit to smokers, report says.

PMID- 11830604
TI  - U.K.'s efforts to improve multidisciplinary care criticized.

PMID- 11830605
TI  - New treatments target metastatic tumors in liver.

PMID- 11830606
TI  - All-cause mortality in randomized trials of cancer screening.
AB  - BACKGROUND: The most widely accepted end point in randomized cancer screening
      trials is disease-specific mortality. The validity of this end point, however,
      rests on the assumption that cause of death can be determined accurately. An
      alternative end point is all-cause mortality, which depends only on the accurate
      ascertainment of deaths and when they occur. We compared disease-specific and all
      cause mortality in published randomized cancer-screening trials to indirectly
      assess the validity of the disease-specific mortality end point. METHODS: We
      examined all 12 published randomized trials of cancer screening for which both
      end points were available (seven of mammography, three of fecal occult blood
      detection, and two of chest x-ray screening for lung cancer). For each randomized
      trial, we subtracted disease-specific mortality observed in the screened group
      from that observed in the control group and all-cause mortality in the screened
      group from that in the control group. We then compared the differences in these
      two mortality measures. RESULTS: In five of the 12 trials, differences in the two
      mortality rates went in opposite directions, suggesting opposite effects of
      screening. In four of these five trials, disease-specific mortality was lower in
      the screened group than in the control group, whereas all-cause mortality was the
      same or higher. In two of the remaining seven trials, the mortality rate
      differences were in the same direction but their magnitudes were inconsistent;
      i.e., the difference in all-cause mortality exceeded the disease-specific
      mortality in the control group. Thus, results of seven of the 12 trials were
      inconsistent in their direction or magnitude. CONCLUSION: Major inconsistencies
      were identified in disease-specific and all-cause mortality end points in
      randomized cancer screening trials. Because all-cause mortality is not affected
      by bias in classifying the cause of death, it should be examined when
      interpreting the results of randomized cancer-screening trials.

PMID- 11830607
TI  - Cisplatin-based therapy for elderly patients with advanced non-small-cell lung
      cancer: implications of Eastern Cooperative Oncology Group 5592, a randomized
      trial.
AB  - BACKGROUND: Older patients, even if fit, are often considered incapable of
      tolerating platinum-based systemic therapy. We performed a retrospective analysis
      of Eastern Cooperative Oncology Group (ECOG) 5592, a phase III randomized trial
      of platinum-based chemotherapy regimens for non-small-cell lung cancer (NSCLC),
      and compared outcomes in enrollees 70 years of age and older with those in
      younger patients. METHODS: ECOG carried out a randomized phase III trial of
      cisplatin plus either etoposide or paclitaxel in chemotherapy-naive NSCLC
      patients with stages III(B) or IV disease. Toxic effects, response rates, and
      survival rates were compared between age groups. All P values were two-sided.
      RESULTS: A total of 574 patients enrolled from August 1993 through December 1994
      were evaluable. Eighty-six (15%) were 70 years old or older. Older patients had a
      higher incidence of cardiovascular (P =.009) and respiratory (P =.04)
      comorbidities and nonanalgesic medication use (P =.02). Leukopenia (P<.001) and
      neuropsychiatric toxicity (P =.002) were more common in elderly men than in
      younger men. Elderly women lost more weight than younger women (P =.006). Other
      toxic effects were similar in older and younger patients. The proportions with
      clinical partial or complete response (21.5% versus 23.3%; Fisher's exact test, P
      =.66), median time to progression (4.37 versus 4.30 months; log-rank test, P
      =.29), and survival distribution (log-rank test, P =.29; median survival, 9.05
      versus 8.53 months; 1-year survival, 38% versus 29%; and 2-year survival, 14%
      versus 12%) were similar in patients younger than 70 years and 70 years old or
      older. Baseline quality-of-life and treatment-outcome indices were similar.
      Equivalent declines over time in functional well-being occurred in both groups.
      CONCLUSION: Response rate, toxicity, and survival in fit, elderly NSCLC patients
      receiving platinum-based treatment appear to be similar to those in younger
      patients, although patients 70 years old or older have more comorbidities and can
      expect more leukopenia and neuropsychiatric toxicity. Advanced age alone should
      not preclude appropriate NSCLC treatment.

PMID- 11830608
TI  - Lung cancer following chemotherapy and radiotherapy for Hodgkin's disease.
AB  - BACKGROUND: Lung cancer is a frequent cause of death in patients cured of
      Hodgkin's disease, but the contributions of chemotherapy, radiotherapy, and
      smoking are not well described. We quantified the risk of treatment-associated
      lung cancer, taking into account tobacco use. METHODS: Within a population-based
      cohort of 19 046 Hodgkin's disease patients (diagnosed from 1965 through 1994), a
      case-control study of lung cancer was conducted. The cumulative amount of
      cytotoxic drugs, the radiation dose to the specific location in the lung where
      cancer developed, and tobacco use were compared for 222 patients who developed
      lung cancer and for 444 matched control patients. All statistical tests were two
      sided. RESULTS: Treatment with alkylating agents without radiotherapy was
      associated with increased lung cancer risk (relative risk [RR] = 4.2; 95%
      confidence interval [CI] = 2.1 to 8.8), as was radiation dose of 5 Gy or more
      without alkylating agents (RR = 5.9; 95% CI = 2.7 to 13.5). Risk increased with
      both increasing number of cycles of alkylating agents and increasing radiation
      dose (P for trend <.001). Among patients treated with mechlorethamine,
      vincristine, procarbazine, and prednisone (MOPP), risk increased with cumulative
      amounts of mechlorethamine and procarbazine (P<.001) when evaluated separately.
      Statistically significantly elevated risks of lung cancer were apparent within 1
      4 years after treatment with alkylating agents, whereas excess risk after
      radiotherapy began 5 years after treatment and persisted for more than 20 years.
      Risk after treatment with alkylating agents and radiotherapy together was as
      expected if individual excess risks were summed. Tobacco use increased lung
      cancer risk more than 20-fold; risks from smoking appeared to multiply risks from
      treatment. CONCLUSIONS: Past treatments with alkylating agents and radiation
      therapy for Hodgkin's disease were associated with an increased risk of lung
      cancer in a dose-dependent and additive fashion. The precise risk estimates,
      however, should be interpreted cautiously, given the possible residual and
      enhancing effects of tobacco.

PMID- 11830609
TI  - Cost-effectiveness of cervical cancer screening: comparison of screening
      policies.
AB  - BACKGROUND: Recommended screening policies for cervical cancer differ widely
      among countries with respect to targeted age range, screening interval, and total
      number of scheduled screening examinations (i.e., Pap smears). We compared the
      efficiency of cervical cancer-screening programs by performing a cost
      effectiveness analysis of cervical cancer-screening policies from high-income
      countries. METHODS: We used the microsimulation screening analysis (MISCAN)
      program to model and determine the costs and effects of almost 500 screening
      policies, some fictitious and some actual (i.e., recommended by national
      guidelines). The costs (in U.S. dollars) and effects (in years of life gained)
      were compared for each policy to identify the most efficient policies. RESULTS:
      There were 15 efficient screening policies (i.e., no alternative policy exists
      that results in more life-years gained for lower costs). For these policies,
      which considered two to 40 total scheduled examinations, the age range expanded
      gradually from 40-52 years to 20-80 years as the screening interval decreased
      from 12 to 1.5 years. For the efficient policies, the predicted gain in life
      expectancy ranged from 11.6 to 32.4 days, compared with a gain of 46 days if
      cervical cancer mortality were eliminated entirely. The average cost
      effectiveness ratios increased from $6700 (for the longest screening interval) to
      $23 900 per life-year gained. For some countries, the recommended screening
      policies were close to efficient, but the cost-effectiveness could be improved by
      reducing the number of scheduled examinations, starting them at later ages, or
      lengthening the screening interval. CONCLUSIONS: The basis for the diversity in
      the screening policies among high-income countries does not appear to relate to
      the screening policies' cost-effectiveness ratios, which are highly sensitive to
      the number of Pap smears offered during a lifetime.

PMID- 11830610
TI  - Dominant negative ATM mutations in breast cancer families.
AB  - BACKGROUND: The ATM gene encoding a putative protein kinase is mutated in ataxia
      telangiectasia (A-T), an autosomal recessive disorder with a predisposition for
      cancer. Studies of A-T families suggest that female heterozygotes have an
      increased risk of breast cancer compared with noncarriers. However, neither
      linkage analyses nor mutation studies have provided supporting evidence for a
      role of ATM in breast cancer predisposition. Nevertheless, two recurrent ATM
      mutations, T7271G and IVS10-6T-->G, reportedly increase the risk of breast
      cancer. We examined these two ATM mutations in a population-based, case-control
      series of breast cancer families and multiple-case breast cancer families.
      METHODS: Five hundred twenty-five or 262 case patients with breast cancer and 381
      or 68 control subjects, respectively, were genotyped for the T7271G and IVS10-6T-
      >G ATM mutations, as were index patients from 76 non-BRCA1/2 multiple-case breast
      cancer families. Linkage and penetrance were analyzed. ATM protein expression and
      kinase activity were analyzed in lymphoblastoid cell lines from mutation
      carriers. All statistical tests were two-sided. RESULTS: In case and control
      subjects unselected for family history of breast cancer, one case patient had the
      T7271G mutation, and none had the IVS10-6T-->G mutation. In three multiple-case
      families, one of these two mutations segregated with breast cancer. The estimated
      average penetrance of the mutations was 60% (95% confidence interval [CI] = 32%
      to 90%) to age 70 years, equivalent to a 15.7-fold (95% CI = 6.4-fold to 38.0
      fold) increased relative risk compared with that of the general population.
      Expression and activity analyses of ATM in heterozygous cell lines indicated that
      both mutations are dominant negative. CONCLUSION: At least two ATM mutations are
      associated with a sufficiently high risk of breast cancer to be found in multiple
      case breast cancer families. Full mutation analysis of the ATM gene in such
      families could help clarify the role of ATM in breast cancer susceptibility.

PMID- 11830611
TI  - Allelic imbalances in human bladder cancer: genome-wide detection with high
      density single-nucleotide polymorphism arrays.
AB  - BACKGROUND: Bladder cancer is characterized by genomic instability. In this
      study, we investigated whether genome-wide screening using single-nucleotide
      polymorphism (SNP) arrays could detect allelic imbalance (loss or gain of at
      least one allele) in bladder cancers. METHODS: For microarray analysis, DNA was
      isolated from microdissected bladder tumors and leukocytes from 11 patients. The
      stage T1 tumor (connective tissue invasive) and the subsequent stage T2-4 tumor
      (muscle invasive) were available from eight of these patients, and only the first
      muscle-invasive stage T2-4 tumor was available from three of the 11 patients. The
      microarray contained 1494 biallelic polymorphic sequences. For microsatellite
      analyses, DNA was isolated from tumors and leukocytes of nine patients with
      primary T2-4 tumors and 13 patients with Ta (noninvasive) tumors. All statistical
      tests were two-sided. RESULTS: We assigned a genotype to 1204 loci, 343 of which
      were heterozygous. Allelic imbalance was detected in known areas of imbalance on
      chromosomes 6, 8, 9, 11, and 17, and a new area of imbalance was detected on the
      p arm of chromosome 6. Microsatellite analysis of nine other T2-4 tumors and 13
      Ta tumors showed that allelic imbalance was more frequent in T2-4 tumors than in
      Ta tumors (P<.001). We detected 8.5 allelic imbalances (median) in 348
      informative loci in T1 tumors and 28 allelic imbalances (median) in 329
      informative loci in T2-4 tumors. When pairs of T1 and T2-4 tumors were analyzed
      from eight patients, 68% of imbalances detected in T1 tumors (146 imbalances)
      occurred in the subsequent T2-4 tumors (99 imbalances). Homozygous TP53 mutations
      were more often associated (P =.005) with high allelic imbalance than with low
      allelic imbalance. CONCLUSION: SNP arrays are feasible for high-throughput,
      genome-wide scanning for allelic imbalances in bladder cancer.

PMID- 11830612
TI  - Use of tanning devices and risk of basal cell and squamous cell skin cancers.
AB  - Use of artificial tanning devices that emit UV radiation, such as tanning lamps
      and tanning beds, has become increasingly popular in the United States. Although
      an excess risk of nonmelanoma skin cancers might be predicted from this exposure,
      little epidemiologic data exist. We conducted a population-based, case-control
      study that included 603 basal cell carcinoma (BCC) case patients, 293 squamous
      cell carcinoma (SCC) case patients, and 540 control subjects. Study participants
      were interviewed in person to obtain information on tanning device use, sun
      exposure history, sun sensitivity, and other risk factors for skin cancer.
      Overall, any use of tanning devices was associated with odds ratios of 2.5 (95%
      confidence interval [CI] = 1.7 to 3.8) for SCC and 1.5 (95% CI = 1.1 to 2.1) for
      BCC. Adjustment for history of sunburns, sunbathing, and sun exposure did not
      affect our results. Our findings suggest that the use of tanning devices may
      contribute to the incidence of nonmelanoma skin cancers. They highlight the need
      to further evaluate the potential risks of BCC and SCC that are associated with
      tanning lamp exposure and the appropriate public health response.

PMID- 11830613
TI  - Re: Pathologic features of prostate cancer found at population-based screening
      with a four-year interval.

PMID- 11830615
TI  - Re: Debate on the link between SV40 and human cancer continues.

PMID- 11830616
TI  - Re: Debate on the link between SV40 and human cancer continues.

PMID- 11830618
TI  - Is intraosseous venography a significant safety measure in performance of
      vertebroplasty?

PMID- 11830619
TI  - Percutaneous vertebroplasty for osteoporotic compression fractures: quantitative
      prospective evaluation of long-term outcomes.
AB  - PURPOSE: Osteoporotic vertebral compression fractures may cause debilitating pain
      that lasts for weeks or months, and which is often neither quickly nor completely
      relieved by conventional conservative therapy. Previous retrospective studies
      have suggested significant and nearly immediate pain relief, as well as rapid and
      sustained functional recovery, after percutaneous polymethylmethacrylate
      vertebroplasty (PPV). This prospective, quantitative study with long-term follow
      up was designed to evaluate the safety and efficacy of PPV as a new treatment for
      patients with osteoporotic vertebral body compression fractures of the lumbar and
      thoracic spine. MATERIALS AND METHODS: PPV was performed in 30 patients with 54
      symptomatic osteoporotic vertebral compression fractures who had a less-than
      satisfactory response to conventional therapy. All procedures were performed by a
      single operator with significant experience in performing PPV. The
      Musculoskeletal Outcomes Data Evaluation and Management Scale (MODEMS) spinal
      intervention questionnaire, which includes the SF-36, was administered to all
      patients before intervention and exactly 2 weeks after the final PPV procedure.
      Pain and disability, treatment expectations and satisfaction, mental function,
      and quality of life were evaluated by four specialized modules, and responses to
      questionnaires preceding treatment were compared to those obtained at follow-up.
      Results of a long-term follow-up questionnaire were collected 15-18 months after
      the final vertebroplasty treatment. RESULTS: Our population consisted of three
      men and 27 women, with a mean age of 79 years. Fifty-four PPV procedures were
      performed for compression fractures in these 30 patients. Significant
      postprocedural improvement in all four MODEMS modules was demonstrated at 2 weeks
      (treatment score, P <.0001; pain and disability, P <.0001; physical function, P
      =.0004; and mental function, P =.0009). A small epidural leak of
      polymethylmethacrylate in one patient was asymptomatic and did not require
      intervention. At long-term follow-up (15-18 mo), 22 of 23 patients responding
      remained satisfied with the outcome of therapy and believed that the procedure
      had provided durable pain relief. Verbal pain scores documented significantly
      diminished back pain at 2 weeks (P <.0001) and again at long-term follow-up when
      compared to baseline (P <.0001). CONCLUSIONS: PPV is a safe and efficacious
      procedure for the relief of pain and disability after osteoporotic vertebral
      compression fractures. Patient satisfaction is high and persists when compared to
      preprocedural expectations; durable pain relief is provided.

PMID- 11830620
TI  - Predictive value of intraosseous venography before percutaneous vertebroplasty.
AB  - PURPOSE: Percutaneous vertebroplasty is a novel approach for treating patients
      with painful vertebral body compression fractures. The use of intraosseous
      venography before the percutaneous injection of polymethylmethacrylate (PMMA) is
      not universally accepted. The purpose of this study was to determine if
      intraosseous venography predicts PMMA flow characteristics when injected into a
      vertebral body. MATERIALS AND METHODS: One hundred thirty-five intraosseous
      venograms were obtained during 96 vertebroplasty procedures (39 thoracic, 57
      lumbar) in 61 patients (49 women, 12 men; age, 36-94 y) over a 32-month period.
      All venograms were obtained by injecting water-soluble contrast material through
      the vertebroplasty needle that had been placed percutaneously via a
      transpedicular approach. The venograms were retrospectively reviewed by the
      authors and compared in a blinded fashion with the subsequent final
      vertebroplasty result. RESULTS: Several venographic patterns were observed:
      bilateral or unilateral marrow blush with or without venous filling, direct
      venous filling, leakage of contrast material through an endplate or cortical
      defect, and stasis within the marrow space. Venograms that demonstrated a
      bilateral marrow blush predicted flow of PMMA across the midline to adequately
      fill the contralateral hemivertebrae 95% of the time (40 of 42 cases). A
      unilateral marrow blush predicted the necessity of a second puncture 97% of the
      time (32 of 33 cases). Intraosseous venography predicted PMMA entering
      endplate/cortical defects in all cases (22 of 22) and venous structures in 29%
      (22 of 75) of cases. Direct venous filling was observed during two vertebroplasty
      procedures and gelatin foam embolization was performed before PMMA instillation.
      Stasis of contrast material in the marrow space was observed in 15 cases.
      Overall, in 83% (80 of 96) of the vertebroplasty procedures, intraosseous
      venography was believed to predict the flow characteristics of PMMA. CONCLUSION:
      Intraosseous venography provides useful information in predicting PMMA flow
      characteristics within the vertebral body and in predicting potential undesirable
      sites of cement deposition, such as through cortical defects and within venous
      structures.

PMID- 11830621
TI  - Serum bilirubin and early mortality after transjugular intrahepatic portosystemic
      shunts: results of a multivariate analysis.
AB  - PURPOSE: To examine the prognostic utility of the serum bilirubin level before
      transjugular intrahepatic portosystemic shunt (TIPS) creation as an independent
      predictor of 30-day mortality in patients who underwent TIPS creation for
      treatment of variceal hemorrhage. MATERIALS AND METHODS: Multiple covariates from
      a cohort of 220 consecutive patients undergoing TIPS creation were analyzed with
      use of univariate and multivariate logistic regression. These included pre-TIPS
      total bilirubin levels, modified Child-Pugh class, APACHE II score, intubation
      status, etiology of liver disease, and acute versus elective shunting. RESULTS:
      The mean pre-TIPS serum total bilirubin level was 3.2 mg/dL (range, 0.4-40.3
      mg/dL). The bilirubin level was <3 mg/dL in 102 patients, > or = 3.0 mg/dL in 58,
      > or = 4.0 mg/dL in 34, and > or = 5.0 mg/dL in 27. Each 1.0-mg/dL increase in
      total bilirubin was associated with 40% greater odds of 30-day mortality (odds
      ratio = 1.4; 95% CI = 1.2-1.7). Using each threshold as its own referent,
      bilirubin levels at or greater than 3.0, 4.0, and 5.0 mg/dL stratified patients
      into increased odds of early death by 5.7, 9.7, and 19.2 times, respectively (all
      P <.001). A pre-TIPS APACHE II score of >18 increased the odds of early death by
      a factor of 5.6 (95% CI = 2.4-8.7); modified Child-Pugh class C (vs classes A and
      B combined) alone increased the odds by a factor of 8.1 (95% CI = 3.6-18.1). Only
      one of 20 patients (5%) with a pre-TIPS bilirubin level >6.0 mg/dL survived more
      than 30 days after TIPS creation. In acutely bleeding patients (n = 122)
      undergoing TIPS creation, bilirubin levels > or = 3.0, > or = 4.0, and > or = 5.0
      mg/dL stratified patients into odds ratios of 4.4, 7.1, and 9.8, respectively,
      compared with 7.1, 13.2, and 9.2 for patients undergoing elective TIPS creation.
      Combining endotracheal intubation (n = 72) and bilirubin strata yielded mortality
      odds of 8.3, 12.5, and 20.8 compared with odds of 2.3, 4.6, and 11.2 in
      nonintubated patients. Combining alcoholic cirrhosis (n = 129) with bilirubin
      levels yielded mortality odds of 8.0, 10.6, and 18.0 compared with other
      etiologies of liver disease (odds ratios = 2.9, 7.3, and 22.7). CONCLUSION: An
      elevated pre-TIPS bilirubin level is a powerful independent predictor of 30-day
      mortality after TIPS creation with a 40% increased risk of death for each 1-mg/dL
      increase above 3.0 mg/dL. The predictive value of this criterion is increased in
      patients who undergo TIPS procedures electively. The magnitude of the effect on
      mortality is similar to that of APACHE II scores and modified Child-Pugh class
      but is simpler to ascertain.

PMID- 11830622
TI  - Mechanical and enzymatic thrombolysis for massive pulmonary embolism.
AB  - PURPOSE: To assess the efficacy and safety of mechanical fragmentation combined
      with intrapulmonary thrombolysis in massive pulmonary thromboembolism (PTE) with
      hemodynamic impairment. MATERIALS AND METHODS: Fifty-nine patients diagnosed with
      massive PTE with hemodynamic impact were treated. The initial clinical symptoms
      were shock in 23 patients (38.9%), syncope in eight (13.5%), and dyspnea at rest
      in 28 (47.4%). Mean O2 saturation was 67.8%. Mean pulmonary artery pressure (PAP)
      was 42.1 mm Hg. During fragmentation, thrombolysis was administered in the form
      of a urokinase bolus of 200,000-500,000 U in 57 patients and 20 mg of recombinant
      tissue plasminogen activator (rt-PA) in two patients. The mean urokinase dose
      used was 2,500,000 IU, whereas the total dose of rt-PA was 100 mg. Heparin sodium
      infusion was performed to reach activated partial thromboplastin time ratios of
      2. The follow-up consisted of clinical assessment, pulmonary scintigraphy, and
      echocardiography. The patients received treatment with dicoumarin for 6 months
      after the procedure. RESULTS: Clinical improvement was seen in 56 patients (94%).
      Three patients died. The mean PAP after the treatment was 21.8 mm Hg. The mean
      posttreatment Miller index was 0.35. Technical success was achieved in all cases
      and clinical symptoms improved in all cases except those in which the patients
      died. Pulmonary scintigraphy showed improved perfusion in all cases.
      Echocardiography was performed after 3-6 months, showing a mean pressure of 22.8
      mm Hg (corrected values). There were no signs of recurrent PTE or arterial
      hypertension in the follow-up. CONCLUSION: The data provided confirm the efficacy
      and safety of mechanical fragmentation and pharmacologic thrombolysis in the
      treatment of massive PTE with hemodynamic impairment, showing improvement of
      symptoms and a decrease in PAP.

PMID- 11830623
TI  - Pelvic congestion syndrome (pelvic venous incompetence): impact of ovarian and
      internal iliac vein embolotherapy on menstrual cycle and chronic pelvic pain.
AB  - PURPOSE: The purpose of this study was to analyze the impact of transcatheter
      embolotherapy on pain perception and menstrual cycle in women with chronic pelvic
      pain caused by the presence of ovarian and pelvic varices (ie, women with pelvic
      congestion syndrome or pelvic venous incompetence). MATERIALS AND METHODS: From
      July 1998 to August 2000, 56 patients (mean age, 32.3 y) were treated for chronic
      pelvic pain. Diagnostic venography of the ovarian veins was followed by
      transcatheter embolotherapy with a sclerosing agent and coils. A second session
      was completed to embolize the internal iliac veins in 43 of 56 patients. Visual
      analog scales (VAS) used to measure pain were administered before embolization
      and at 3-, 6-, and 12-month follow-up. Questionnaires regarding menstrual history
      were used as part of the postprocedural analysis. RESULTS: Percutaneous
      transcatheter embolotherapy of ovarian and pelvic varices was technically
      successful in 56 of 56 patients (100%); three patients developed recurrent
      varices, two of whom were treated with repeat transcatheter embolotherapy. Two
      patients, early in the experience, had complications in which coils placed in the
      internal iliac veins embolized to the pulmonary circulation; the coils were
      snared without clinical sequelae. On the VAS, the mean baseline pain level was
      7.8 (range, 3.2-9.8; n = 56); at 3-month follow-up, it was 4.2 (range, 0.0-7.2; n
      = 56); at 6 months, 3.8 (range, 0.0-6.7; n = 41); and at 12 months, 2.7 (range,
      0.0-6.9; n = 32). Differences were significant (P <.001) between baseline pain
      levels and those at all follow-up intervals (ie, 3, 6, and 12 months). The mean
      decrease in VAS was 5.1 (65% decrease). The clinical follow-up in this series
      ranged between 6 and 38 months; the mean was 22.1 months. Regarding the impact of
      embolization on menstruation, all 24 patients responding to questionnaires
      indicated no change in menstrual cycle. CONCLUSION: For patients with
      ovarian/internal iliac varices, transcatheter embolotherapy provides a
      nonsurgical treatment option. There is a significant decrease in pain based on
      VAS without any notable impact on menstrual cycle.

PMID- 11830624
TI  - Risk of deep venous thrombosis associated with chest versus arm central venous
      subcutaneous port catheters: a 5-year single-institution retrospective study.
AB  - PURPOSE: To determine the risk of deep venous thrombosis (DVT) in patients
      undergoing placement of central (chest) versus peripheral (arm) ports. MATERIALS
      AND METHODS: Between January 1996 and December 2000, a total of 440 implantable
      chest or arm ports were placed in 422 patients. Data pertaining to the first port
      placed for each patient was analyzed. Ports were placed for chemotherapy (n =
      415) or blood transfusion (n = 7). Subset analysis was performed, taking into
      consideration whether patients received prophylactic or therapeutic doses of
      warfarin sodium (Coumadin), to determine if there was any difference in the
      incidence of DVT between patients undergoing some form of anticoagulation versus
      those undergoing none. The medical records of these patients were reviewed to
      determine outcome with reference to development of DVT. RESULTS: In 273 chest
      ports placed, there were 13 (4.8%) instances of DVT; in 149 peripheral ports,
      there were 17 (11.4%). Censoring data on patients receiving some form of
      anticoagulation, the respective incidences were eight of 245 (3.3%) and 14 of 129
      (10.9%). With use of Kaplan-Meier analysis and log-rank tests to examine
      comparisons of interest, the probability of thrombosis occurring over a period of
      180 days was higher with peripheral ports irrespective of Coumadin use (P =.007
      for all patients considered, P =.002 when analyzed only for those not receiving
      Coumadin). The difference in incidence of thrombosis for all ports between
      patients receiving Coumadin versus those not receiving Coumadin was not
      significant. CONCLUSIONS: Compared to chest ports, peripheral ports are
      associated with a significantly higher incidence of DVT.

PMID- 11830625
TI  - Percutaneous microwave tumor coagulation for hepatocellular carcinomas with
      interruption of segmental hepatic blood flow.
AB  - PURPOSE: To assess the effect of hepatic artery occlusion with or without hepatic
      venous outflow interruption on coagulation diameter during percutaneous microwave
      coagulation therapy (PMCT) for hepatocellular carcinoma (HCC) by a prospective
      and randomized trial. MATERIALS AND METHODS: Thirty-one patients with 36 HCCs (10
      38 mm in diameter) were randomly separated into two treatment groups as follows:
      group 1 (14 tumors in 14 patients) was treated with PMCT in conjunction with both
      segmental hepatic artery embolization with gelatin sponge particles and temporary
      interruption of hepatic venous flow by means of a 6-F balloon catheter to reduce
      the portal venous flow; group 2 (22 tumors in 17 patients) was treated with PMCT
      with segmental hepatic artery embolization only. PMCT under ultrasound (US)
      guidance was performed with 2,450 MHz of microwave frequency at 40-60 W and a
      needle applicator 1.6 mm in diameter. The coagulated area was measured at the
      maximum diameter perpendicular to the needle tract on enhanced computed
      tomography (CT) performed immediately after PMCT. The local effect of the
      treatment was evaluated by follow-up enhanced CT (6-33 mo). RESULTS: Patients in
      group 1 had a significantly larger coagulation area (mean +/-SD = 42.9 mm +/-
      8.3), with coagulation times of 5.3 min +/- 1.4, than patients in group 2 (32.6
      mm +/- 8.0), with coagulation times of 4.2 min +/- 1.3 (P <.05). Follow-up
      enhanced CT showed no local enhancement of the tumor, indicating complete
      necrosis and no local recurrence, except for four tumors. There were no major
      complications after PMCT except liver abscess that developed after PMCT in one
      patient with pneumobilia. CONCLUSIONS: PMCT with combined hepatic arterial
      embolization and temporary hepatic venous flow interruption can coagulate
      significantly larger volumes of tumor than PMCT with only hepatic arterial
      embolization.

PMID- 11830626
TI  - Repeat interventions for maintenance of transjugular intrahepatic portosystemic
      shunt function in patients with Budd-Chiari syndrome.
AB  - The authors report the role of transjugular intrahepatic portosystemic shunts
      (TIPS) and consecutive interventions, including brachytherapy (n = 2) and stent
      graft placement (n = 3), to increase secondary patency and consequently postpone
      orthotopic liver transplantation (OLT) in the treatment of Budd-Chiari syndrome
      in eight patients. Two patients (with hematologic diseases) died 2 weeks after
      the TIPS procedure. Median follow-up in the six survivors was 42.5 months (range,
      11-79 mo). Multiple TIPS occlusions occurred in three patients (range, 2-7
      revisions). Reocclusions occurred despite brachytherapy and Hemobahn stent-graft
      placement and necessitated OLT in one patient. Revision-free patency was achieved
      in the other two patients after VIATORR stent-graft placement (16 and 32 months
      after TIPS creation). All patients with stable TIPS (n = 5) are without ascites,
      no liver failure occurred, and no patients are currently on the transplant list.

PMID- 11830627
TI  - Use of the percutaneous thrombolytic device for the treatment of thrombosed
      pseudoaneurysms during mechanical thrombectomy of hemodialysis grafts.
AB  - This article describes a method to remove thrombus from pseudoaneurysms
      associated with hemodialysis grafts during a percutaneous mechanical thrombectomy
      procedure. This effective and easily performed technique involves manual
      compression of the pseudoaneurysm during activation of the Arrow Percutaneous
      Thrombolytic Device. The authors describe their clinical experience with use of
      this technique to treat 18 patients during percutaneous mechanical thrombectomy
      procedures. In addition, the development, morphology, and management of
      hemodialysis graft-related pseudoaneurysms are discussed.

PMID- 11830628
TI  - Percutaneous treatment of a gastrocutaneous fistula after gastrostomy tube
      removal.
AB  - Gastrocutaneous fistula formation is a potential complication resulting from
      nonsurgical gastrostomy or gastrojejunostomy tube removal. Limited success in
      conservative treatment has been achieved with either mechanical obstruction of
      the tract or pharmacologically based increase in gastric pH and improvement of
      gastric emptying. A case of successful conservative percutaneous treatment of a
      gastrocutaneous fistula with use of the sequence of initial tract de
      epithelialization followed by direct tract sclerosis and mechanical obstruction
      is presented in this article.

PMID- 11830629
TI  - Reactivation of herpes zoster after liver biopsy.
AB  - A patient developed reactivation of herpes zoster infection (shingles) after a
      routine liver biopsy. Reactivation of herpes is often related to trauma. This
      entity should be considered when patients report postbiopsy pain inappropriate to
      the procedure. If the typical rash of shingles develops, antiviral therapy should
      be considered.

PMID- 11830630
TI  - Percutaneous treatment of iatrogenic iliocaval fistula related to endograft
      placement for abdominal aortic aneurysm.
AB  - The authors report a case of iatrogenic dissection occurring during endovascular
      treatment of an abdominal aortic aneurysm. The dissection was related to
      catheterization maneuvers that led to the development of a symptomatic
      arteriovenous fistula, which was successfully closed by coil embolization.

PMID- 11830631
TI  - Angiosarcoma of the aorta.

PMID- 11830632
TI  - Re: Value of three-dimensional US for optimizing guidance for ablating focal
      liver tumors.

PMID- 11830633
TI  - Re: Use of an Amplatz gooseneck snare as a target for collateral neck vein
      dialysis catheter placement.

PMID- 11830634
TI  - Measuring tubulin content in Toxoplasma gondii: a comparison of laser-scanning
      confocal and wide-field fluorescence microscopy.
AB  - Toxoplasma gondii is an intracellular parasite that proliferates within most
      nucleated cells, an important human pathogen, and a model for the study of human
      and veterinary parasitic infections. We used a stable yellow fluorescent protein
      alpha-tubulin transgenic line to determine the structure of the microtubule
      cytoskeleton in T. gondii. Imaging of living yellow fluorescent protein-alpha
      tubulin parasites by laser-scanning confocal microscopy (LSCM) failed to resolve
      the 22 subpellicular microtubules characteristic of the parasite cytoskeleton. To
      understand this result, we analyzed sources of noise in the LSCM and identified
      illumination fluctuations on time scales from microseconds to hours that
      introduce significant amounts of noise. We confirmed that weakly fluorescent
      structures could not be imaged in LSCM by using fluorescent bead standards. By
      contrast, wide-field microscopy (WFM) did visualize weak fluorescent standards
      and the individual microtubules of the parasite cytoskeleton. We therefore
      measured the fluorescence per unit length of microtubule by using WFM and used
      this information to estimate the tubulin content of the conoid (a structure
      important for T. gondii infection) and in the mitotic spindle pole. The conoid
      contains sufficient tubulin for approximately 10 microtubule segments of 0.5
      microm length, indicating that tubulin forms the structural core of the
      organelle. We also show that the T. gondii mitotic spindle contains approximately
      1 microtubule per chromosome. This analysis expands the understanding of
      structures used for invasion and intracellular proliferation by an important
      human pathogen and shows the advantage of WFM combined with image deconvolution
      over LSCM for quantitative studies of weakly fluorescent structures in moderately
      thin living cells.

PMID- 11830636
TI  - Glacial meltwater dynamics in coastal waters west of the Antarctic peninsula.
AB  - The annual advance and retreat of sea ice has been considered a major physical
      determinant of spatial and temporal changes in the structure of the Antarctic
      coastal marine ecosystem. However, the role of glacial meltwater on the
      hydrography of the Antarctic Peninsula ecosystem has been largely ignored, and
      the resulting biological effects have only been considered within a few
      kilometers from shore. Through several lines of evidence collected in conjunction
      with the Palmer Station Long-Term Ecological Research Project, we show that the
      freshening and warming of the coastal surface water over the summer months is
      influenced not solely by sea ice melt, as suggested by the literature, but
      largely by the influx of glacial meltwater. Moreover, the seasonal variability in
      the amount and extent of the glacial meltwater plume plays a critical role in the
      functioning of the biota by influencing the physical dynamics of the water (e.g.,
      water column stratification, nearshore turbidity). From nearly a decade of
      observations (1991-1999), the presence of surface meltwater is correlated not
      only to phytoplankton blooms nearshore, but spatially over 100 km offshore. The
      amount of meltwater will also have important secondary effects on the ecosystem
      by influencing the timing of sea ice formation. Because air temperatures are
      statistically increasing along the Antarctic Peninsula region, the presence of
      glacial meltwater is likely to become more prevalent in these surface waters and
      continue to play an ever-increasing role in driving this fragile ecosystem.

PMID- 11830635
TI  - Lesions of the nucleus basalis magnocellularis induced by 192 IgG-saporin block
      memory enhancement with posttraining norepinephrine in the basolateral amygdala.
AB  - Extensive evidence indicates that drugs and stress hormones act in the
      basolateral amygdala (BLA) to modulate memory consolidation. The BLA projects to
      the nucleus basalis magnocellularis (NBM), which sends broad cholinergic
      projections to the neocortex. NBM-cortex projections have been implicated in
      learning, memory storage, and plasticity. The current study investigated whether
      the cholinergic NBM-cortex projections are involved in BLA-mediated modulation of
      memory consolidation. Bilateral cholinergic cell lesions of the NBM were induced
      in rats with infusions of 192 IgG-saporin (0.1 microg/0.5 microl per side).
      Additionally, cannulae were implanted bilaterally in the BLA. One week after
      surgery, the rats were trained in an inhibitory avoidance task and, immediately
      after training, norepinephrine (0.3 microg, 1.0 microg, or 3.0 microg in 0.2
      microl) or vehicle (PBS) was infused bilaterally into the BLA. Norepinephrine
      infusions produced a dose-dependent enhancement of 48-h retention (0.3 microg and
      1.0 microg doses enhanced) in nonlesioned rats but did not affect retention in
      NBM-lesioned rats. Choline acetyltransferase assays of frontal and occipital
      cortices confirmed the NBM lesions. These findings indicate that cholinergic NBM
      cortex projections are required for BLA-mediated modulation of memory
      consolidation.

PMID- 11830637
TI  - Solution structure and stability of the anti-sigma factor AsiA: implications for
      novel functions.
AB  - Anti-sigma factors regulate prokaryotic gene expression through interactions with
      specific sigma factors. The bacteriophage T4 anti-sigma factor AsiA is a
      molecular switch that both inhibits transcription from bacterial promoters and
      phage early promoters and promotes transcription at phage middle promoters
      through its interaction with the primary sigma factor of Escherichia coli,
      sigma(70). AsiA is an all-helical, symmetric dimer in solution. The solution
      structure of the AsiA dimer reveals a novel helical fold for the protomer.
      Furthermore, the AsiA protomer, surprisingly, contains a helix-turn-helix DNA
      binding motif, predicting a potential new role for AsiA. The AsiA dimer interface
      includes a substantial hydrophobic component, and results of hydrogen/deuterium
      exchange studies suggest that the dimer interface is the most stable region of
      the AsiA dimer. In addition, the residues that form the dimer interface are those
      that are involved in binding to sigma(70). The results promote a model whereby
      the AsiA dimer maintains the active hydrophobic surfaces and delivers them to
      sigma(70), where an AsiA protomer is displaced from the dimer via the interaction
      of sigma(70) with the same residues in AsiA that constitute the dimer interface.

PMID- 11830638
TI  - Centrosome amplification drives chromosomal instability in breast tumor
      development.
AB  - Earlier studies of invasive breast tumors have shown that 60-80% are aneuploid
      and approximately 80% exhibit amplified centrosomes. In this study, we
      investigated the relationship of centrosome amplification with aneuploidy,
      chromosomal instability, p53 mutation, and loss of differentiation in human
      breast tumors. Twenty invasive breast tumors and seven normal breast tissues were
      analyzed by fluorescence in situ hybridization with centromeric probes to
      chromosomes 3, 7, and 17. We analyzed these tumors for both aneuploidy and
      unstable karyotypes as determined by chromosomal instability. The results were
      then tested for correlation with three measures of centrosome amplification:
      centrosome size, centrosome number, and centrosome microtubule nucleation
      capacity. Centrosome size and centrosome number both showed a positive,
      significant, linear correlation with aneuploidy and chromosomal instability.
      Microtubule nucleation capacity showed no such correlation, but did correlate
      significantly with loss of tissue differentiation. Centrosome amplification was
      detected in in situ ductal carcinomas, suggesting that centrosome amplification
      is an early event in these lesions. Centrosome amplification and chromosomal
      instability occurred independently of p53 mutation, whereas p53 mutation was
      associated with a significant increase in centrosome microtubule nucleation
      capacity. Together, these results demonstrate that independent aspects of
      centrosome amplification correlate with chromosomal instability and loss of
      tissue differentiation and may be involved in tumor development and progression.
      These results further suggest that aspects of centrosome amplification may have
      clinical diagnostic and/or prognostic value and that the centrosome may be a
      potential target for cancer therapy.

PMID- 11830639
TI  - An iron-regulated sortase anchors a class of surface protein during
      Staphylococcus aureus pathogenesis.
AB  - Sortase (SrtA), an enzyme that anchors surface proteins to the cell wall of Gram
      positive bacteria, cleaves sorting signals at the LPXTG motif. We have identified
      a second sortase (SrtB) in the Gram-positive pathogen Staphylococcus aureus that
      is required for anchoring of a surface protein with a NPQTN motif. Purified SrtB
      cleaves NPQTN-bearing peptides in vitro, and a srtB mutant is defective in the
      persistence of animal infections. srtB is part of an iron-regulated locus called
      iron-responsive surface determinants (isd), which also contains a ferrichrome
      transporter and surface proteins with NPQTN and LPXTG motifs. Cell wall-anchored
      surface proteins and the isd locus seem involved in a novel mechanism of iron
      acquisition that is important for bacterial pathogenesis.

PMID- 11830640
TI  - A poxvirus-like type IB topoisomerase family in bacteria.
AB  - We report that diverse species of bacteria encode a type IB DNA topoisomerase
      that resembles vaccinia virus topoisomerase. Deinococcus radiodurans
      topoisomerase IB (DraTopIB), an exemplary member of this family, relaxes
      supercoiled DNA in the absence of a divalent cation or ATP. DraTopIB has a
      compact size (346 aa) and is a monomer in solution. Mutational analysis shows
      that the active site of DraTopIB is composed of the same constellation of
      catalytic side chains as the vaccinia enzyme. Sequence comparisons and limited
      proteolysis suggest that their folds are conserved. These findings imply an
      intimate evolutionary relationship between the poxvirus and bacterial type IB
      enzymes, and they engender a scheme for the evolution of topoisomerase IB and
      tyrosine recombinases from a common ancestral strand transferase in the bacterial
      domain. Remarkably, bacteria that possess topoisomerase IB appear to lack DNA
      topoisomerase III.

PMID- 11830641
TI  - Binding of Escherichia coli adhesin AfaE to CD55 triggers cell-surface expression
      of the MHC class I-related molecule MICA.
AB  - MICA are distant homologs of MHC class I molecules expressed in the normal
      intestinal epithelium. They are ligands of the NKG2D activating receptor
      expressed on most gammadelta T cells, CD8+ alphabeta T cells, and natural killer
      cells and therefore play a critical role in innate immune responses. We
      investigated MICA cell-surface expression on infection of epithelial cell lines
      by enteric bacteria and show here that MICA expression can be markedly increased
      by bacteria of the diffusely adherent Escherichia coli diarrheagenic group. This
      effect is mediated by the specific interaction between bacterial adhesin AfaE and
      its cellular receptor, CD55, or decay-accelerating factor. It is extremely rapid
      after AfaE binding, consistent with a stress-induced signal. MICA induction on
      epithelial cells triggered IFN-gamma release by the NKG2D expressing natural
      killer cell line NKL. This host-bacteria interaction pathway could play a role in
      the pathogenesis of inflammatory bowel disease, a condition that implicates a
      bacterial trigger in genetically susceptible individuals. This was supported by
      the increased MICA expression at the surface of epithelial cells in colonic
      biopsies from Crohn's disease-affected patients compared with controls.

PMID- 11830642
TI  - Caenorhabditis elegans DNA mismatch repair gene msh-2 is required for
      microsatellite stability and maintenance of genome integrity.
AB  - Mismatch repair genes are important in maintaining the fidelity of DNA
      replication. To determine the function of the Caenorhabditis elegans homologue of
      the MSH2 mismatch repair gene (msh-2), we isolated a strain of C. elegans with an
      insertion of the transposable element Tc1 within msh-2. Early-passage msh-2
      mutants were similar to wild-type worms with regard to lifespan and meiotic
      chromosome segregation but had slightly reduced fertility. The mutant worms had
      reduced DNA damage-induced germ-line apoptosis after genotoxic stress. The msh-2
      mutants also had elevated levels of microsatellite instability and increased
      rates of reversion of the dominant unc-58(e665) mutation. In addition, serially
      passaged cultures of msh-2 worms died out much more quickly than those of wild
      type worms. These results demonstrate that msh-2 function in C. elegans is
      important in regulating both short- and long-term genomic stability.

PMID- 11830643
TI  - Amplification-mutagenesis: evidence that "directed" adaptive mutation and general
      hypermutability result from growth with a selected gene amplification.
AB  - When a particular lac mutant of Escherichia coli starves in the presence of
      lactose, nongrowing cells appear to direct mutations preferentially to sites that
      allow growth (adaptive mutation). This observation suggested that growth
      limitation stimulates mutability. Evidence is provided here that this behavior is
      actually caused by a standard Darwinian process in which natural selection acts
      in three sequential steps. First, growth limitation favors growth of a
      subpopulation with an amplification of the mutant lac gene; next, it favors cells
      with a lac(+) revertant allele within the amplified array. Finally, it favors
      loss of mutant copies until a stable haploid lac(+) revertant arises and
      overgrows the colony. By increasing the lac copy number, selection enhances the
      likelihood of reversion within each developing clone. This sequence of events
      appears to direct mutations to useful sites. General mutagenesis is a side-effect
      of growth with an amplification (SOS induction). The F' plasmid, which carries
      lac, contributes by stimulating gene duplication and amplification. Selective
      stress has no direct effect on mutation rate or target specificity, but acts to
      favor a succession of cell types with progressively improved growth on lactose.
      The sequence of events--amplification, mutation, segregation--may help to explain
      both the origins of some cancers and the evolution of new genes under selection.

PMID- 11830644
TI  - Surface sensing and adhesion of Escherichia coli controlled by the Cpx-signaling
      pathway.
AB  - Bacterial adhesion is an important initial step in biofilm formation, which may
      cause problems in medical, environmental, and industrial settings. In spite of
      obvious phenotypic differences between attached and planktonic cells, knowledge
      about the genetic basis for these differences and how adhesion-induced changes
      are mediated is limited. The Cpx two-component signal transduction pathway
      responds specifically to stress caused by disturbances in the cell envelope and
      activates genes encoding periplasmic protein folding and degrading factors. Here,
      we address the role of the Cpx-signaling pathway in sensing and responding to the
      physical change occurring during adhesion of Escherichia coli to surfaces. We
      present evidence that the expression of Cpx-regulated genes is induced during
      initial adhesion of E. coli to abiotic surfaces. This induction is specifically
      observed upon attachment of stationary-phase cells to hydrophobic surfaces.
      Moreover, surface-induced activity of the Cpx response requires NlpE, an outer
      membrane lipoprotein, which has previously been shown to induce the Cpx system
      when overproduced. The importance of a functional Cpx response during adhesion is
      further supported by the fact that a dramatically lower number of cells attach to
      the surface and dynamic cell-surface interactions as measured by a quartz crystal
      microbalance technique are altered when the CpxRA pathway is disrupted. The
      defects in adhesion exhibited by the cpxR and nlpE mutants were strikingly
      similar to those of wild-type cells in which protein synthesis was inhibited,
      suggesting that the Cpx pathway plays a key role in the regulation of adhesion
      induced gene expression.

PMID- 11830645
TI  - Regulation of the tyrosine kinase Itk by the peptidyl-prolyl isomerase
      cyclophilin A.
AB  - Interleukin-2 tyrosine kinase (Itk) is a nonreceptor protein tyrosine kinase of
      the Tec family that participates in the intracellular signaling events leading to
      T cell activation. Tec family members contain the conserved SH3, SH2, and
      catalytic domains common to many kinase families, but they are distinguished by
      unique sequences outside of this region. The mechanism by which Itk and related
      Tec kinases are regulated is not well understood. Our studies indicate that Itk
      catalytic activity is inhibited by the peptidyl prolyl isomerase activity of
      cyclophilin A (CypA). NMR structural studies combined with mutational analysis
      show that a proline-dependent conformational switch within the Itk SH2 domain
      regulates substrate recognition and mediates regulatory interactions with the
      active site of CypA. CypA and Itk form a stable complex in Jurkat T cells that is
      disrupted by treatment with cyclosporin A. Moreover, the phosphorylation levels
      of Itk and a downstream substrate of Itk, PLCgamma1, are increased in Jurkat T
      cells that have been treated with cyclosporin A. These findings support a novel
      mode of tyrosine kinase regulation for a Tec family member and provide a
      molecular basis for understanding a cellular function of the ubiquitous peptidyl
      prolyl isomerase, CypA.

PMID- 11830646
TI  - Identification of a functional role for lipid asymmetry in biological membranes:
      Phosphatidylserine-skeletal protein interactions modulate membrane stability.
AB  - Asymmetric distribution of phospholipids is ubiquitous in the plasma membranes of
      many eukaryotic cells. The majority of the aminophospholipids are located in the
      inner leaflet whereas the cholinephospholipids are localized predominantly in the
      outer leaflet. Several functional roles for asymmetric phospholipid distribution
      in plasma membranes have been suggested. Disruption of lipid asymmetry creates a
      procoagulant surface on platelets and serves as a trigger for macrophage
      recognition of apoptotic cells. Furthermore, the dynamic process of phospholipid
      translocation regulates important cellular events such as membrane budding and
      endocytosis. In the present study, we used the red cell membrane as the model
      system to explore the contribution of phospholipid asymmetry to the maintenance
      of membrane mechanical properties. We prepared two different types of membranes
      in terms of their phospholipid distribution, one in which phospholipids were
      scrambled and the other in which the asymmetric distribution of phospholipids was
      maintained and quantitated their mechanical properties. We documented that
      maintenance of asymmetric distribution of phospholipids resulted in improved
      membrane mechanical stability. The greater difficulty in extracting the spectrin
      actin complex at low-ionic strength from the membranes with asymmetric
      phospholipid distribution further suggested the involvement of interactions
      between aminophospholipids in the inner leaflet and skeletal proteins in
      modulating mechanical stability of the red cell membrane. These findings have
      enabled us to document a functional role of lipid asymmetry in regulating
      membrane material properties.

PMID- 11830647
TI  - A peptide derived from alpha-fetoprotein prevents the growth of estrogen
      dependent human breast cancers sensitive and resistant to tamoxifen.
AB  - An 8-mer peptide (EMTOVNOG) derived from alpha-fetoprotein was compared with
      tamoxifen for activity against growth of human breast cancer xenografts implanted
      in immune-deficient mice. Both peptide and tamoxifen prevented growth of estrogen
      receptor-positive MCF-7 and T47D human breast cancer xenografts. A subline of MCF
      7, made resistant to tamoxifen by a 6-month exposure to this drug in culture, was
      found to be resistant to tamoxifen in vivo. Peptide completely prevented the
      xenograft growth of this tamoxifen-resistant subline of MCF-7. Neither peptide
      nor tamoxifen was effective in slowing the xenograft growth of the estrogen
      receptor-negative MDA-MB-231 human breast cancer. A worrisome side effect of
      tamoxifen is its hypertrophic effect on the uterus. In this study, tamoxifen was
      shown to stimulate the growth of the immature mouse uterus in vivo, and the
      peptide significantly inhibited tamoxifen's uterotrophic effect. The mechanism of
      action of peptide is different from that of tamoxifen in that the peptide does
      not interfere with the binding of [(3)H]estradiol to the estrogen receptor. In
      conclusion, alpha-fetoprotein-derived peptide appears to be a novel agent that
      interferes with the growth of tamoxifen-sensitive as well as tamoxifen-resistant
      estrogen-receptor-positive human breast cancers; it inhibits the uterotrophic
      side effect of tamoxifen and, thus, it may be useful in combination with or in
      place of tamoxifen for treatment of estrogen-receptor-positive human breast
      cancers.

PMID- 11830648
TI  - Viewing protein folding from many perspectives.

PMID- 11830649
TI  - Unstable molecules form stable tissues.

PMID- 11830650
TI  - The methylator meets the terminator.

PMID- 11830651
TI  - Antigen-presenting cells control T cell proliferation by regulating amino acid
      availability.

PMID- 11830652
TI  - Location alters tRNA identity: Trypanosoma brucei's cytosolic elongator tRNAMet
      is both the initiator and elongator in mitochondria.

PMID- 11830653
TI  - Dissecting the molecular mechanisms of olfaction in a malaria-vector mosquito.

PMID- 11830655
TI  - Stochastic and mesoscopic models for tropical convection.
AB  - A new way to parametrize certain aspects of tropical convection through
      stochastic and mesoscopic models is developed here. The technical idea is to
      adapt tools from statistical physics and materials science to model important
      unresolved features of tropical convection. This new strategy consists of
      modeling the unresolved effects of convective inhibition in a coarse mesh
      mesoscopic parametrization through a "heat bath" model involving a stochastic
      spin flip model with very natural interaction rules for convective inhibition
      combined with a suitable external potential defined by the coarse mesh values. In
      turn, the values of the order parameter from this heat bath alter the vertical
      mass flux in regions of deep convection. Both stochastic and systematic
      deterministic mesoscopic parametrizations are developed here. The deterministic
      mesoscopic models derived in this fashion exhibit new phenomena such as multiple
      radiative equilibria in suitable parameter regimes. The simplest first numerical
      experiments reported here with the mesoscopic deterministic parametrization
      qualitatively reproduce several key features of the observational record
      regarding convectively coupled tropical waves. The systematic stochastic modeling
      strategy proposed here could also be very useful for capturing other features of
      tropical convection such as those involving cloud radiation feedbacks.

PMID- 11830656
TI  - The calculation of transport properties in quantum liquids using the maximum
      entropy numerical analytic continuation method: application to liquid para
      hydrogen.
AB  - We present a method based on augmenting an exact relation between a frequency
      dependent diffusion constant and the imaginary time velocity autocorrelation
      function, combined with the maximum entropy numerical analytic continuation
      approach to study transport properties in quantum liquids. The method is applied
      to the case of liquid para-hydrogen at two thermodynamic state points: a liquid
      near the triple point and a high-temperature liquid. Good agreement for the self
      diffusion constant and for the real-time velocity autocorrelation function is
      obtained in comparison to experimental measurements and other theoretical
      predictions. Improvement of the methodology and future applications are
      discussed.

PMID- 11830654
TI  - Calcium signaling: a tale for all seasons.
AB  - An experiment performed in London nearly 120 years ago, which by today's
      standards would be considered unacceptably sloppy, marked the beginning of the
      calcium (Ca(2+)) signaling saga. Sidney Ringer [Ringer, S. (1883) J. Physiol. 4,
      29-43] was studying the contraction of isolated rat hearts. In earlier
      experiments, Ringer had suspended them in a saline medium for which he admitted
      to having used London tap water, which is hard: The hearts contracted
      beautifully. When he proceeded to replace the tap water with distilled water, he
      made a startling finding: The beating of the hearts became progressively weaker,
      and stopped altogether after about 20 min. To maintain contraction, he found it
      necessary to add Ca(2+) salts to the suspension medium. Thus, Ringer had
      serendipitously discovered that Ca(2+), hitherto exclusively considered as a
      structural element, was active in a tissue that has nothing to do with bone or
      teeth, and performed there a completely novel function: It carried the signal
      that initiated heart contraction. It was a landmark observation, which should
      have immediately aroused wide interest. Unexpectedly, however, for decades it
      attracted no particular attention. Occasionally, farsighted pioneers argued
      forcefully for a messenger role of Ca(2+), offering compelling experimental
      evidence. Among them, one could quote L. V. Heilbrunn [Heilbrunn, L. V. (1940)
      Physiol. Zool. 13, 88-94], who contracted frog muscle fibers by applying Ca(2+)
      salts to their cut ends, but not to their surfaces. Heilbrunn correctly concluded
      that Ca(2+) had diffused from the cut ends to the internal contractile elements
      to elicit their contraction. One could also quote K. Bailey [Bailey, K. (1942)
      Biochem. J. 36, 121-139], who showed that the ATPase activity of myosin was
      strongly activated by Ca(2+) (but not by Mg(2+)), and concluded that the
      liberation of Ca(2+) in the neighborhood of the myosin controlled muscle
      contraction. Clearly, enough evidence was there, but only a handful of people had
      the vision to see it and to foresee its far-reaching implications. Perhaps no
      better example of clairvoyance can be offered than the quip by O. Loewy in 1959:
      "Ja Kalzium, das ist alles!"

PMID- 11830657
TI  - Product dependence and bifunctionality compromise the ultrasensitivity of signal
      transduction cascades.
AB  - Covalent modification cycles are ubiquitous. Theoretical studies have suggested
      that they serve to increase sensitivity. However, this suggestion has not been
      corroborated experimentally in vivo. Here, we demonstrate that the assumptions of
      the theoretical studies, i.e., irreversibility and absence of product inhibition,
      were not trivial: when the conversion reactions are close to equilibrium or
      saturated by their product, "zero-order" ultrasensitivity disappears. For high
      sensitivities to arise, not only substrate saturation (zero-order) but also high
      equilibrium constants and low product saturation are required. Many covalent
      modification cycles are catalyzed by one bifunctional 'ambiguous' enzyme rather
      than by two independent proteins. This makes high substrate concentration and low
      product concentration for both reactions of the cycle inconsistent; such
      modification cycles cannot have high responses. Defining signal strength as
      ratios of modified (e.g., phosphorylated) over unmodified protein, signal-to
      signal response sensitivity equals 1: signal strength should remain constant
      along a cascade of ambiguous modification cycles. We also show that the total
      concentration of a signalling effector protein cannot affect the signal emanating
      from a modification cycle catalyzed by an ambiguous enzyme if the ratio of the
      two forms of the effector protein is not altered. This finding may explain the
      experimental result that the pivotal signal transduction protein PII plus its
      paralogue GlnK do not control steady-state N-signal transduction in Escherichia
      coli. It also rationalizes the absence of strong phenotypes for many signal
      transduction proteins. Emphasis on extent of modification of these proteins is
      perhaps more urgent than transcriptome analysis.

PMID- 11830658
TI  - Discrimination against purine-pyrimidine mispairs in the polymerase active site
      of DNA polymerase I: a structural explanation.
AB  - We previously identified five derivatives of Klenow fragment DNA polymerase that
      have lower fidelity because of amino acid substitutions in the polymerase active
      site. One of these has alanine substituted for the invariant Glu-710, whose side
      chain interacts with the deoxyribose of the incoming dNTP. Here we show that the
      E710A enzyme has reduced fidelity for five of the 12 possible mismatches. All but
      one of these involve misinsertion of pyrimidines, including two transition
      mismatches A-dCTP and G-dTTP. In contrast, E710A polymerase error rates for the
      reciprocal C-dATP and T-dGTP transition mismatches were similar to those of the
      wild-type enzyme. The kinetics of formation of correct base pairs and transition
      mismatches by the wild-type and E710A polymerases, combined with information on
      the structure of the DNA polymerase active site and the asymmetry of wobble base
      pairs, provides a plausible explanation for the differential effects of the E710A
      mutation on fidelity. The data suggest that the Glu-710 side chain plays a
      pivotal role in excluding wobble base pairs between template pyrimidines and
      purine triphosphates by steric clash. Moreover, this same side chain enhances the
      stability of incoming correct dNTPs, such that loss of this interaction on
      removal of the side chain leads to lower selectivity against mismatches involving
      incoming pyrimidines.

PMID- 11830659
TI  - Structural diversity of heparan sulfate binding domains in chemokines.
AB  - Heparan sulfate (HS) molecules are ubiquitous in animal tissues where they
      function as ligands that are dramatically involved in the regulation of the
      proteins they bind. Of these, chemokines are a family of small proteins with many
      biological functions. Their well-conserved monomeric structure can associate in
      various oligomeric forms especially in the presence of HS. Application of protein
      surface analysis and energy calculations to all known chemokine structures leads
      to the proposal that four different binding modes are created by the folding and
      oligomerization of these proteins. So, based on the present state of our
      knowledge, four different clusters of amino acids should be involved in the
      recognition process. Our results help to rationalize how unique sequences of HS
      specifically bind any given chemokine. The conclusions open the route for a
      rational design of compounds of therapeutical interest that could influence
      chemokine activity.

PMID- 11830660
TI  - Translocation of a functional protein by a voltage-dependent ion channel.
AB  - The voltage-dependent gating of the colicin channel involves a substantial
      structural rearrangement that results in the transfer of about 35% of the 200
      residues in its pore-forming domain across the membrane. This transfer appears to
      represent an unusual type of protein translocation that does not depend on a
      large, multimeric, protein pore. To investigate the ability of this system to
      transport arbitrary proteins, we made use of a pair of strongly interacting
      proteins, either of which could serve as a translocated cargo or as a probe to
      detect the other. Here we show that both an 86-residue and a 134-residue
      hydrophilic protein inserted into the translocated segment of colicin A are
      themselves translocated and are functional on the trans side of the bilayer. The
      disparate features of these proteins suggest that the colicin channel has a
      general protein translocation mechanism.

PMID- 11830661
TI  - Stable "zeta" peptides that act as potent antagonists of the high-affinity IgE
      receptor.
AB  - Recently we described a family of peptides, unrelated in sequence to IgE, that
      form stable beta-hairpins in solution and inhibit IgE activity in the microM
      range [Nakamura, G. R., Starovasnik, M. A., Reynolds, M. E. & Lowman, H. B.
      (2001) Biochemistry 40, 9828-9835]. Using an expanded set of peptide-phage
      libraries, we found a simpler motif, X(2)CPX(2)CYX, for binding to the high
      affinity IgE receptor. In solution, one of these peptides spontaneously formed a
      covalent antiparallel dimer. We subsequently linked these monomers in a single
      chain construct on phage and optimized receptor binding. Ultimately, peptides
      with 30 nM affinity were produced. NMR studies showed that the peptide adopts a
      stable fold consisting of two "zeta" (zeta)-shaped moieties. Structure-activity
      analyses reveal a single binding site created by the zeta-dimer, with two
      tyrosine residues important for structural stability and two proline residues
      important for Fc epsilon RI binding. The peptides inhibit histamine release from
      cultured cells and are extremely stable in biological fluids. The zeta peptides
      appear to act as competitive IgE inhibitors and suggest possibilities for design
      of novel IgE antagonists.

PMID- 11830662
TI  - Muscle-derived hematopoietic stem cells are hematopoietic in origin.
AB  - It has recently been shown that mononuclear cells from murine skeletal muscle
      contain the potential to repopulate all major peripheral blood lineages in
      lethally irradiated mice, but the origin of this activity is unknown. We have
      fractionated muscle cells on the basis of hematopoietic markers to show that the
      active population exclusively expresses the hematopoietic stem cell antigens Sca
      1 and CD45. Muscle cells obtained from 6- to 8-week-old C57BL/6-CD45.1 mice and
      enriched for cells expressing Sca-1 and CD45 were able to generate hematopoietic
      but not myogenic colonies in vitro and repopulated multiple hematopoietic
      lineages of lethally irradiated C57BL/6-CD45.2 mice. These data show that muscle
      derived hematopoietic stem cells are likely derived from the hematopoietic system
      and are a result not of transdifferentiation of myogenic stem cells but instead
      of the presence of substantial numbers of hematopoietic stem cells in the muscle.
      Although CD45-negative cells were highly myogenic in vitro and in vivo, CD45
      positive muscle-derived cells displayed only very limited myogenic activity and
      only in vivo.

PMID- 11830663
TI  - Projecting the future of the U.S. carbon sink.
AB  - Atmospheric and ground-based methods agree on the presence of a carbon sink in
      the coterminous United States (the United States minus Alaska and Hawaii), and
      the primary causes for the sink recently have been identified. Projecting the
      future behavior of the sink is necessary for projecting future net emissions.
      Here we use two models, the Ecosystem Demography model and a second simpler
      empirically based model (Miami Land Use History), to estimate the spatio-temporal
      patterns of ecosystem carbon stocks and fluxes resulting from land-use changes
      and fire suppression from 1700 to 2100. Our results are compared with other
      historical reconstructions of ecosystem carbon fluxes and to a detailed carbon
      budget for the 1980s. Our projections indicate that the ecosystem recovery
      processes that are primarily responsible for the contemporary U.S. carbon sink
      will slow over the next century, resulting in a significant reduction of the
      sink. The projected rate of decrease depends strongly on scenarios of future land
      use and the long-term effectiveness of fire suppression.

PMID- 11830665
TI  - Complementary whole-genome technologies reveal the cellular response to
      proteasome inhibition by PS-341.
AB  - Although the biochemical targets of most drugs are known, the biological
      consequences of their actions are typically less well understood. In this study,
      we have used two whole-genome technologies in Saccharomyces cerevisiae to
      determine the cellular impact of the proteasome inhibitor PS-341. By combining
      population genomics, the screening of a comprehensive panel of bar-coded mutant
      strains, and transcript profiling, we have identified the genes and pathways most
      affected by proteasome inhibition. Many of these function in regulated protein
      degradation or a subset of mitotic activities. In addition, we identified Rpn4p
      as the transcription factor most responsible for the cell's ability to compensate
      for proteasome inhibition. Used together, these complementary technologies
      provide a general and powerful means to elucidate the cellular ramifications of
      drug treatment.

PMID- 11830666
TI  - The murine CCR3 receptor regulates both the role of eosinophils and mast cells in
      allergen-induced airway inflammation and hyperresponsiveness.
AB  - CCR3 is a chemokine receptor initially thought specific to eosinophils but
      subsequently identified on TH2 cell subsets, basophils, mast cells, neural
      tissue, and some epithelia. Because of the prominent role of these cells in
      allergic disease, including asthma, we generated mice deficient in CCR3 to
      determine its contribution in a model of allergic airway disease. Here we show
      that CCR3 is important for the basal trafficking of eosinophils to the intestinal
      mucosa but not the lung. In contrast, CCR3 disruption significantly curtails
      eosinophil recruitment to the lung after allergen challenge, with the majority of
      the eosinophils being arrested in the subendothelial space. Further, a role for
      CCR3 in mast cell homing has been identified; after sensitization and allergen
      challenge, we find increased numbers of intraepithelial mast cells in the trachea
      of knockout mice. Physiologically, we find that the net result of these complex
      cell fates after sensitization and allergen challenge is a paradoxical increase
      in airway responsiveness to cholinergic stimulation. These data underscore a more
      complex role for CCR3 in allergic disease than was anticipated.

PMID- 11830667
TI  - Cooperation of multiple signaling pathways in CD40-regulated gene expression in B
      lymphocytes.
AB  - CD40/CD40L interaction is essential for multiple biological events in T dependent
      humoral immune responses, including B cell survival and proliferation, germinal
      center and memory B cell formation, and antibody isotype switching and affinity
      maturation. By using high-density microarrays, we examined gene expression in
      primary mouse B lymphocytes after multiple time points of CD40L stimulation. In
      addition to genes involved in cell survival and growth, which are also induced by
      other mitogens such as lipopolysaccharide, CD40L specifically activated genes
      involved in germinal center formation and T cell costimulatory molecules that
      facilitate T dependent humoral immunity. Next, by examining the roles of
      individual CD40-activated signal transduction pathways, we dissected the overall
      CD40-mediated response into genes independently regulated by the individual
      pathways or collectively by all pathways. We also found that gene down-regulation
      is a significant part of the overall response and that the p38 pathway plays an
      important role in this process, whereas the NF-kappa B pathway is important for
      the up-regulation of primary response genes. Our finding of overlapping
      independent control of gene expression modules by different pathways suggests, in
      principle, that distinct biological behaviors that depend on distinct gene
      expression subsets can be manipulated by targeting specific signaling pathways.

PMID- 11830668
TI  - Targeting the prostate for destruction through a vascular address.
AB  - Organ specific drug targeting was explored in mice as a possible alternative to
      surgery to treat prostate diseases. Peptides that specifically recognize the
      vasculature in the prostate were identified from phage-displayed peptide
      libraries by selecting for phage capable of homing into the prostate after an
      i.v. injection. One of the phage selected in this manner homed to the prostate 10
      15 times more than to other organs. Unselected phage did not show this
      preference. The phage bound also to vasculature in the human prostate. The
      peptide displayed by the prostate-homing phage, SMSIARL (single letter code), was
      synthesized and shown to inhibit the homing of the phage when co-injected into
      mice with the phage. Systemic treatment of mice with a chimeric peptide
      consisting of the SMSIARL homing peptide, linked to a proapoptotic peptide that
      disrupts mitochondrial membranes, caused tissue destruction in the prostate, but
      not in other organs. The chimeric peptide delayed the development of the cancers
      in prostate cancer-prone transgenic mice (TRAMP mice). These results suggest that
      it may be possible to develop an alternative to surgical prostate resection and
      that such a treatment may also reduce future cancer risk.

PMID- 11830664
TI  - The analysis of 100 genes supports the grouping of three highly divergent
      amoebae: Dictyostelium, Entamoeba, and Mastigamoeba.
AB  - The phylogenetic relationships of amoebae are poorly resolved. To address this
      difficult question, we have sequenced 1,280 expressed sequence tags from
      Mastigamoeba balamuthi and assembled a large data set containing 123 genes for
      representatives of three phenotypically highly divergent major amoeboid lineages:
      Pelobionta, Entamoebidae, and Mycetozoa. Phylogenetic reconstruction was
      performed on approximately 25,000 aa positions for 30 species by using maximum
      likelihood approaches. All well-established eukaryotic groups were recovered with
      high statistical support, validating our approach. Interestingly, the three
      amoeboid lineages strongly clustered together in agreement with the Conosa
      hypothesis [as defined by T. Cavalier-Smith (1998) Biol. Rev. Cambridge Philos.
      Soc. 73, 203-266]. Two amitochondriate amoebae, the free-living Mastigamoeba and
      the human parasite Entamoeba, formed a significant sister group to the exclusion
      of the mycetozoan Dictyostelium. This result suggested that a part of the
      reductive process in the evolution of Entamoeba (e.g., loss of typical
      mitochondria) occurred in its free-living ancestors. Applying this inexpensive
      expressed sequence tag approach to many other lineages will surely improve our
      understanding of eukaryotic evolution.

PMID- 11830669
TI  - The Brucella suis virB operon is induced intracellularly in macrophages.
AB  - A type IV secretion system similar to the VirB system of the phytopathogen
      Agrobacterium tumefaciens is essential for the intracellular survival and
      multiplication of the mammalian pathogen Brucella. Reverse transcriptase-PCR
      showed that the 12 genes encoding the Brucella suis VirB system form an operon.
      Semiquantitative measurements of virB mRNA levels by slot blotting showed that
      transcription of the virB operon, but not the flanking genes, is regulated by
      environmental factors in vitro. Flow cytometry used to measure green fluorescent
      protein expression from the virB promoter confirmed the data from slot blots.
      Fluorescence-activated cell sorter analysis and fluorescence microscopy showed
      that the virB promoter is induced in macrophages within 3 h after infection.
      Induction only occurred once the bacteria were inside the cells, and phagosome
      acidification was shown to be the major signal inducing intracellular expression.
      Because phagosome acidification is essential for the intracellular multiplication
      of Brucella, we suggest that it is the signal that triggers the secretion of
      unknown effector molecules. These effector molecules play a role in the
      remodeling of the phagosome to create the unique intracellular compartment in
      which Brucella replicates.

PMID- 11830670
TI  - The murMN operon: a functional link between antibiotic resistance and antibiotic
      tolerance in Streptococcuspneumoniae.
AB  - Inactivation of the recently identified murMN operon in penicillin-resistant
      strains of Streptococcus pneumoniae was shown already to cause two major effects:
      elimination of branched-structured muropeptides from the cell wall and complete
      loss of penicillin resistance. We now show that cells with inactivated murMN also
      have a third phenotype: an increased susceptibility to lysis when exposed to low
      concentrations of fosfomycin, d-cycloserine, vancomycin, and nisin, indicating a
      wide-spectrum hypersensitivity to inhibitors of both early and late stages of
      cell wall biosynthesis. Mutants of murMN also lysed faster than the parental
      strain when treated with the detergent deoxycholate. Several different alleles of
      murM cloned in plasmid pLS578 and introduced into a murM deletion mutant of the
      penicillin-resistant strain Pen6 were able to reconstitute each one of the three
      mutant phenotypes: the highly branched cell wall structure, original high level
      of penicillin resistance, and normal sensitivity to lysis. In a penicillin
      susceptible strain the same experiments caused increased concentration of cell
      wall branched peptides and suppression of sensitivity to antibiotic induced
      lysis. The observations suggest that the murMN operon plays a key role in the
      regulation of a stress-response pathway that can be triggered by perturbation of
      cell wall biosynthesis in S. pneumoniae.

PMID- 11830671
TI  - DNA microarray analysis of differential gene expression in Borrelia burgdorferi,
      the Lyme disease spirochete.
AB  - DNA microarrays were used to survey the adaptive genetic responses of Borrelia
      burgdorferi (Bb) B31, the Lyme disease spirochete, when grown under conditions
      analogous to those found in unfed ticks (UTs), fed ticks (FTs), or during
      mammalian host adaptation (Bb in dialysis membrane chambers implanted in rats).
      Microarrays contained 95.4% of the predicted B31 genes, 150 (8.6%) of which were
      differentially regulated (changes of > or = 1.8-fold) among the three growth
      conditions. A substantial proportion (46%) of the differentially regulated genes
      encoded proteins with predicted export signals (29% from predicted lipoproteins),
      emphasizing the importance to Bb of modulating its extracellular proteome. For
      B31 cultivated at the more restrictive UT condition, microarray data provided
      evidence of a bacterial stringent response and factors that restrict cell
      division. A large proportion of genes were responsive to the FT growth condition,
      wherein increased temperature and reduced pH were prominent environmental
      parameters. A surprising theme, supported by cluster analysis, was that many of
      the gene expression changes induced during the FT growth condition were transient
      and largely tempered as B31 adapted to the mammalian host, suggesting that once
      Bb gains entry and adapts to mammalian tissues, fewer differentially regulated
      genes are exploited. It therefore would seem that although widely dissimilar, the
      UT and dialysis membrane chamber growth conditions promote more static patterns
      of gene expression in Bb. The microarray data thus provide a basis for
      formulating new testable hypotheses regarding the life cycle of Bb and attaining
      a more complete understanding of many aspects of Bb's complex parasitic
      strategies.

PMID- 11830672
TI  - The capsular polysaccharide of Enterococcus faecalis and its relationship to
      other polysaccharides in the cell wall.
AB  - With the goal of identifying and characterizing traits of Enterococcus faecalis
      that play key roles in human disease, we identified an operon specifying
      synthesis of a capsular carbohydrate of the type most commonly expressed by
      clinical isolates. This surface-exposed carbohydrate consists of glycerol
      phosphate, glucose, and galactose residues, and its biosynthesis is encoded by a
      determinant that includes 11 ORFs. Insertional inactivation of genes in this
      pathway yielded mutants with enhanced susceptibility to phagocytic killing in
      vitro and compromised in the ability to persist in regional lymph nodes in vivo.

PMID- 11830673
TI  - The SNARE protein SNAP-25 is linked to fast calcium triggering of exocytosis.
AB  - Synchronous neurotransmission depends on the tight coupling between Ca(2+) influx
      and fusion of neurotransmitter-filled vesicles with the plasma membrane. The
      vesicular soluble N-ethylmaleimide-sensitive factor attachment protein receptor
      (SNARE) protein synaptobrevin 2 and the plasma membrane SNAREs syntaxin 1 and
      synaptosomal protein of 25 kDa (SNAP-25) are essential for calcium-triggered
      exocytosis. However, the link between calcium triggering and SNARE function
      remains elusive. Here we describe mutations in two sites on the surface of the
      SNARE complex formed by acidic and hydrophilic residues of SNAP-25 and
      synaptobrevin 2, which were found to coordinate divalent cations in the neuronal
      SNARE complex crystal structure. By reducing the net charge of the site in SNAP
      25 we identify a mutation that interferes with calcium triggering of exocytosis
      when overexpressed in chromaffin cells. Exocytosis was elicited by photorelease
      of calcium from a calcium cage and evaluated by using patch-clamp capacitance
      measurements at millisecond time resolution. We present a method for monitoring
      the dependence of exocytotic rate upon calcium concentration at the release site
      and demonstrate that the mutation decreased the steepness of this relationship,
      indicating that the number of sequential calcium-binding steps preceding
      exocytosis is reduced by one. We conclude that the SNARE complex is linked
      directly to calcium triggering of exocytosis, most likely in a complex with
      auxiliary proteins.

PMID- 11830674
TI  - Circulating relaxin acts on subfornical organ neurons to stimulate water drinking
      in the rat.
AB  - Relaxin, a peptide hormone secreted by the corpus luteum during pregnancy, exerts
      actions on reproductive tissues such as the pubic symphysis, uterus, and cervix.
      It may also influence body fluid balance by actions on the brain to stimulate
      thirst and vasopressin secretion. We mapped the sites in the brain that are
      activated by i.v. infusion of a dipsogenic dose of relaxin (25 microg/h) by
      immunohistochemically detecting Fos expression. Relaxin administration resulted
      in increased Fos expression in the subfornical organ (SFO), organum vasculosum of
      the lamina terminalis (OVLT), median preoptic nucleus, and magnocellular neurons
      in the supraoptic and paraventricular nuclei. Ablation of the SFO abolished
      relaxin-induced water drinking, but did not prevent increased Fos expression in
      the OVLT, supraoptic or paraventricular nuclei. Although ablation of the OVLT did
      not inhibit relaxin-induced drinking, it did cause a large reduction in Fos
      expression in the supraoptic nucleus and posterior magnocellular subdivision of
      the paraventricular nucleus. In vitro single-unit recording of electrical
      activity of neurons in isolated slices of the SFO showed that relaxin (10(-7) M)
      added to the perfusion medium caused marked and prolonged increase in neuronal
      activity. Most of these neurons also responded to 10(-7) M angiotensin II. The
      data indicate that blood-borne relaxin can directly stimulate neurons in the SFO
      to initiate water drinking. It is likely that circulating relaxin also stimulates
      neurons in the OVLT that influence vasopressin secretion. These two
      circumventricular organs that lack a blood-brain barrier may have regulatory
      influences on fluid balance during pregnancy in rats.

PMID- 11830675
TI  - A gene encoding a protein modified by the phytohormone indoleacetic acid.
AB  - We show that the expression of an indole-3-acetic acid (IAA)-modified protein
      from bean seed, IAP1, is correlated to the developmental period of rapid growth
      during seed development. Moreover, this protein undergoes rapid degradation
      during germination. The gene for IAP1, the most abundant protein covalently
      modified by IAA (iap1, GenBank accession no. ) was isolated and cloned from bush
      bean (Phaseolus vulgaris) seeds. The 957-bp sequence encodes a 35-kDa
      polypeptide. IAA-modified proteins represent a distinct class of conjugated
      phytohormones and appear in bean to be the major form of auxin in seeds. IAA
      proteins also are found at other stages of development in bean plants. Our
      immunological and analytical data suggest that auxin modification of a small
      class of proteins may be a feature common to many plants.

PMID- 11830676
TI  - Enhanced ADP-glucose pyrophosphorylase activity in wheat endosperm increases seed
      yield.
AB  - Yield in cereals is a function of seed number and weight; both parameters are
      largely controlled by seed sink strength. The allosteric enzyme ADP-glucose
      pyrophosphorylase (AGP) plays a key role in regulating starch biosynthesis in
      cereal seeds and is likely the most important determinant of seed sink strength.
      Plant AGPs are heterotetrameric, consisting of two large and two small subunits.
      We transformed wheat (Triticum aestivum L.) with a modified form of the maize
      (Zea mays L.) Shrunken2 gene (Sh2r6hs), which encodes an altered AGP large
      subunit. The altered large subunit gives rise to a maize AGP heterotetramer with
      decreased sensitivity to its negative allosteric effector, orthophosphate, and
      more stable interactions between large and small subunits. The Sh2r6hs transgene
      was still functional after five generations in wheat. Developing seeds from
      Sh2r6hs transgenic wheat exhibited increased AGP activity in the presence of a
      range of orthophosphate concentrations in vitro. Transgenic Sh2r6hs wheat lines
      produced on average 38% more seed weight per plant. Total plant biomass was
      increased by 31% in Sh2r6hs plants. Results indicate increased availability and
      utilization of resources in response to enhanced seed sink strength, increasing
      seed yield, and total plant biomass.

PMID- 11830678
TI  - Telemedicine in Hong Kong.

PMID- 11830677
TI  - Global organization of the Wordnet lexicon.
AB  - The lexicon consists of a set of word meanings and their semantic relationships.
      A systematic representation of the English lexicon based in psycholinguistic
      considerations has been put together in the database Wordnet in a long-term
      collaborative effort. We present here a quantitative study of the graph structure
      of Wordnet to understand the global organization of the lexicon. Semantic links
      follow power-law, scale-invariant behaviors typical of self-organizing networks.
      Polysemy (the ambiguity of an individual word) is one of the links in the
      semantic network, relating the different meanings of a common word. Polysemous
      links have a profound impact in the organization of the semantic graph,
      conforming it as a small world network, with clusters of high traffic (hubs)
      representing abstract concepts such as line, head, or circle. Our results show
      that: (i) Wordnet has global properties common to many self-organized systems,
      and (ii) polysemy organizes the semantic graph in a compact and categorical
      representation, in a way that may explain the ubiquity of polysemy across
      languages.

PMID- 11830679
TI  - Hong Kong clinical trials published in Medline between 1987 and 1996.
AB  - The aims of this study were to determine the number of randomised clinical trials
      where the correspondence address included the words 'Hong Kong' for the years of
      publication between January 1987 and December 1996, and to study their
      characteristics: year of publication, disease area, sample size, and
      correspondence address of the department and institute; MEDLINE EXPRESS was used
      for the search. A total of 5605 publications were identified, of which only 170
      (3.0%) were found to be randomised clinical trials. No significant increase in
      the proportion of randomised clinical trials could be seen during the decade of
      publication (P>0.05). Approximatley 50% of the trials had a small sample size
      (fewer than 75 subjects) and most randomised clinical trials were performed in
      the field of internal medicine, followed by surgery, and obstetrics and
      gynaecology (total, 69%). The predominant research area was gastrointestinal
      disease (34%). Despite a relatively high academic output from Hong Kong, the
      number of randomised clinical trials has not increased much during the decade.

PMID- 11830680
TI  - Megaloblastic anaemia in Chinese patients: a review of 52 cases.
AB  - A prospective study of Chinese patients with megaloblastic anaemia was conducted
      at the Pamela Youde Nethersole Eastern Hospital from 1 May 1994 to 31 August
      1997. Megaloblastic anaemia was diagnosed in 57 patients, 52 of whom were
      eligible for further evaluation. The median age of these 52 patients was 73.5
      years and the male to female ratio was 1.08:1. The serum cobalamin level (median,
      56 ng/L) was low in 46 (86.5%) patients. In five (9.6%) patients, both serum
      cobalamin and red blood cell folate concentrations were low. Isolated low red
      blood cell folate level was demonstrated in one (1.9%) patient. Serum antibodies
      against intrinsic factor and gastric parietal cells were detected in 32 (61.5%)
      and 26 (50.0%) patients, respectively; 19 (36.5%) patients had both types of
      antibody. The aetiology of megaloblastic anaemia included pernicious anaemia in
      39 (75%) patients, postgastrectomy vitamin B12 deficiency in five (9.6%)
      patients, and nutritional deficiency in two (3.8%) patients; the cause was
      undetermined in six (11.5%) patients.

PMID- 11830681
TI  - Microvascular free flap reconstruction: the Kwong Wah Hospital experience.
AB  - The early experience of free flap reconstruction in a regional plastic surgery
      unit was reviewed. Forty-seven free flap surgical procedures were performed for
      46 patients during a 2-year period from 1 January 1995 to 31 December 1996 in a
      regional plastic surgery centre that specialises in head and neck, and breast
      reconstruction. Twenty-six free transverse rectus abdominus myocutaneous flaps
      were performed for 25 breast cancer patients. Head and neck reconstructions were
      mostly performed after surgical ablation of oral and pharyngeal cancers. A
      variety of free flaps were used, including fibular osteocutaneous flaps, radial
      forearm fasciocutaneous flaps, jejunal grafts, and rectus abdominus
      musculocutaneous flaps. Lateral arm fasciocutaneous and scapular fasciocutaneous
      flaps were used for three patients who had foot ulceration. The success rate of
      free flap transfer was 94%. Flap loss was found in three patients who had pedicle
      complications that were due to traction, kinking, and thrombosis. There was no
      mortality in the series. The most common morbidity was wound infection. Two
      thirds of the free flap transfers were uneventful. Seven (15%) patients had major
      complications that required re-operation. Institutional support was essential for
      the development of microvascular surgery.

PMID- 11830682
TI  - Treatment of dystonia with botulinum A toxin: a retrospective study of 170
      patients.
AB  - OBJECTIVE: Botulinum A toxin has been reported to provide excellent symptomatic
      relief for patients with dystonia. To analyse the treatment, complications, and
      outcome of patients receiving botulinum A toxin injection, the case records of
      170 patients attending the Botox Clinic at the Kwong Wah Hospital from 1 December
      1992 to 31 December 1996 were reviewed. Of these 170 patients, 130 (76.5%) had
      idiopathic hemifacial spasm, 18 (10.6%) had blepharospasm, 18 (10.6%) had
      spasmodic torticollis, and 4 (2.4%) had generalised or focal limb dystonia. One
      hundred and sixty-six (97.6%) patients were Chinese. The average dose of
      botulinum A toxin required for an optimal response was 14.54 U for those with
      hemifacial spasm, 49.64 U for those blepharospasm, and 137 U for those with
      spasmodic torticollis. Among patients with hemifacial spasm, 103 (81.7%) gave a
      good response, 21 (16.7%) gave a partial response, and there was no response in
      two (1.6%) patients. The corresponding figures for patients with blepharospasm
      were 7 (38.9%), 10 (55.6%), and 1 (5.6%), respectively, and for those with
      spasmodic torticollis, the figure were 6 (37.5%), 6 (37.5%), and 4 (2.5%),
      respectively. Complications from botulinum A toxin injection were rare (less than
      10%), minor, transient, and usually dose-related. In conclusion, idiopathic
      hemifacial spasm was the most common type of movement disorder encountered in our
      Botox Clinic and botulinum A toxin injection was safe and effective in the
      majority of patients.

PMID- 11830683
TI  - Fine needle aspiration of breast masses: an analysis of 1533 cases in private
      practice.
AB  - The diagnostic efficacy of fine needle aspiration cytology of breast masses and
      the causes for unsatisfactory specimens in private practices were investigated in
      Hong Kong. All specimens that were submitted to the histopathology unit at the
      Canossa Hospital between 1 January 1996 and 30 April 1997 formed the basis of
      this report. A total of 1533 specimens were received from 1447 patients; 274
      (17.8%) cases were unsatisfactory for assessment, 1080 (70.4%) were benign, 51
      (3.3%) atypical, 19 (1.2%) suspicious, and 67 (4.4%) malignant. The specimens
      were submitted by 105 doctors, who each performed between 1 and 561 smears. The
      proportion of unsatisfactory samples was high for doctors who performed an
      occasional fine needle aspiration (48%; overall mean, 25%). Histological
      correlation was available in 165 cases. The overall sensitivity was 79%,
      specificity 98%, positive predictive value (including the 'suspicious' category)
      92%, and negative predictive value 94%. Two false positive cases that were
      reported as suspicious were found to be fibroadenomata following subsequent
      excision biopsy. No adverse clinical outcomes were recorded for the false
      positive cases. There were six false negative cases (reported as a cyst in one
      case, benign in two cases, and atypical in three cases). The results compared
      favourably with published data and affirmed the effectiveness of the test in
      private practice.

PMID- 11830684
TI  - Telemedicine: academic and professional aspects.
AB  - Doctors have recently gained substantial experience of using telemedical
      applications for consultations, education and training, and conferences. What is
      still lacking is systematic evaluation of these new approaches compared with
      traditional procedures. Trials involving consultations for diagnostic,
      monitoring, and interpretative purposes should be blinded and multicentred, and
      should include tests of patient satisfaction as well as macro-economic
      considerations. The quality of educational programmes and conferences should be
      documented and compared with traditional teaching methods. International
      standards need to be developed for such evaluations, to allow comparisons between
      trials performed at national and international levels. Hong Kong is in a good
      position to contribute to these developments because of a well-integrated health
      care system and excellent telecommunication facilities. Through telemedicine,
      Hong Kong could resume a leading global position in the use of advanced
      information technology.

PMID- 11830685
TI  - The impact of teleradiology on the inter-hospital transfer of neurosurgical
      patients and their outcome.
AB  - The impact of teleradiology technology used in the management of neurosurgical
      emergencies between district general hospitals and tertiary neurosurgical centres
      is reviewed. Its effect on clinical management such as diagnostic accuracy and
      the prevention of secondary insults has been shown to be favourable. Problems and
      possible future developments are also discussed.

PMID- 11830686
TI  - Teleconferencing in endoscopic surgery.
AB  - The traditional methods of information dissemination by publication in journals
      and the classical model of instruction by apprenticeship have not been able to
      keep pace with the rapid advances in the fields of therapeutic endoscopy and
      laparascopic surgery. The advances in communications technology have made it
      possible to transmit images of operative procedures over long distances. In
      recent years, teaching workshops where procedures are demonstrated in a real-time
      fashion have become very popular. This article discusses the logistics,
      limitations, and problems that may be encountered in conducting such workshops.

PMID- 11830687
TI  - OphthWeb---cost-effective telemedicine for ophthalmology.
AB  - 'OphthWeb' is an ophthalmic electronic medical record that can be accessed
      locally and globally via the Internet. OphthWeb can provide secure multimedia
      patient data to doctors, patients, and health care providers at any time and in
      any place. Patients have secured access to their own records in the convenience
      of their homes or during any emergency at any time or place around the world.
      OphthWeb provides interactive educational information and answers frequently
      asked questions by way of multimedia images on the Worldwide Web. A data
      transmission trial was conducted between the Xiamen Eye Centre in the Fujian
      province in southern China and Singapore. Clinical records, voice messages, and
      fundus and slit-lamp images were transmitted from Xiamen, and an off-line
      dialogue by e-mail and Internet-relay chat was conducted. The time delay from
      transmission to receipt was 30 minutes, which would be adequate to respond to
      most ophthalmic emergencies. This pilot project will promote computer literacy
      among doctors, and inter-institutional interaction in the health care profession.
      OphthWeb can provide telemedicine and electronic medical records at a low cost
      and great convenience.

PMID- 11830688
TI  - Deep vein thrombosis and pulmonary embolism in the Chinese population.
AB  - Deep vein thrombosis and pulmonary embolism is a well-recognised major health
      problem in the West. There is a deep-rooted belief among clinicians that deep
      vein thrombosis is rare in Asians, particularly in the Chinese population.
      However, it appears that the incidence of venous thrombosis and pulmonary
      embolism is increasing in Chinese patients. Prophylaxis reduces the incidence of
      venous thrombosis by 66% and of pulmonary embolism by 50%--- prophylaxis should
      therefore be considered for Chinese patients who have a high risk of developing
      postoperative deep vein thrombosis. This report reviews the current literature on
      this subject.

PMID- 11830689
TI  - Estate doctors and policy on family medicine.
AB  - Estate doctors were dismayed by the Hong Kong Council of Social Service's
      publication of a survey of patients leaving clinics after consultations. The
      data, however, show high levels of satisfaction from patients who consulted
      estate doctors, and most people (and their families) attended one doctor by
      choice, contrary to widespread perception of 'doctor shopping' in Hong Kong.
      Aspects of care in Hong Kong could be improved and include short consultation
      times, limited discussion, and frequent usage of short courses of medication.
      There is segregation of care: estate doctors see more working-age peolple and
      their families, while out-patient departments see older and unemployed people.
      The report concluded that further development of family medicine is needed in
      Hong Kong---a conclusion that the Estate Doctors Association shares. The survey
      demonstrates again some underlying problems of primary medical care in Hong Kong-
      -problems which are largely related to the expectation and learned habits among
      both doctors and patients, and which must change for Hong Kong health care to
      reach the level expected in a modern, developed society.

PMID- 11830690
TI  - Chemotherapy of tuberculosis in Hong Kong: a consensus statement The Tuberculosis
      Control Coordinating Committee (Department of Health) and the Tuberculosis
      Subcommittee of the Coordinating Committee in Internal Medicine (Hospital
      Authority), Hong Kong.
AB  - This consensus statement is prepared primarily as a concise reference for
      tuberculosis chemotherapy in Hong Kong. Treatment should be tailored to patients
      individually, expert advice should be sought when necessary, and 'directly
      observed treatment' should be used where possible. A 6-month regimen is
      recommended as the initial treatment of uncomplicated pulmonary tuberculosis and
      a 9-month regimen is recommended for retreatment. Patients with disease that is
      resistant to isoniazid or rifampicin may require modified regimens. Multidrug
      resistant tuberculosis should be managed in specialised centres, using multiple
      drugs as guided by in vitro susceptibility tests. Recommended regimens to treat
      extrapulmonary tuberculosis are based on limited current evidence, although
      shorter regimens may be acceptable when better evidence emerges. A longer
      duration of treatment is required for diabetic, immuno-compromised, or silicotic
      patients. During pregnancy, streptomycin should be avoided; the safety profiles
      of second-line drugs have not yet been ascertained. Hepatotoxic drugs should be
      used with caution in patients with liver dysfunction, and extra caution and
      dosage reductions are required if streptomycin and ethambutol are used in
      patients with renal impairment.

PMID- 11830691
TI  - Parvovirus B19-associated hydrops fetalis: the first confirmed case in Hong Kong.
AB  - We describe a case of asymptomatic human parvovirus B19 infection during
      pregnancy that led to hydrops fetalis and foetal death. The diagnosis was
      confirmed by the presence of parvovirus B19-specific IgM antibodies in the
      maternal serum and the pathognomonic findings, which showed intranuclear
      eosinophilic viral inclusions and margination of chromatin in foetal cells of
      haemopoietic lineage. Details of clinical, virological, and histological findings
      are presented. Difficulties in confirming the diagnosis of parvovirus B19
      infection in Hong Kong are discussed.

PMID- 11830692
TI  - Acute encephalitis complicating rubella.
AB  - During an epidemic of rubella in Hong Kong between October 1996 and June 1997,
      four male patients presented with rubella complicated by encephalitis, the
      symptoms of which started 1 to 5 days after the appearance of the rash
      characteristic of rubella. Two patients recovered completely within 1 week and
      one complained of a slight impairment of short-term memory. Severe cerebral
      oedema, and herniation across the brainstem and cerebellum developed in the
      fourth patient, who died 15 days later. The presence of serum immunoglobulin M
      antibody against rubella virus was demonstrated in all four patients; one patient
      also had immunoglobulin M antibody against rubella virus in his cerebrospinal
      fluid. No virus could be isolated during post-mortem examination of the fourth
      patient.

PMID- 11830693
TI  - A multidisciplinary approach to salvage the 'unsalvageable' foot.
AB  - Extensive tissue loss in a weight-bearing area of the foot almost invariably
      heralds limb loss. We report on a 74-year-old man with diabetes mellitus who had
      an ischaemic foot that was affected by prolonged pressure, which resulted in a
      necrotic heel. After two sessions of debridement, the calcaneum became exposed.
      Amputation was initially suggested but was refused by the patient. The foot was
      subsequently salvaged by staged operations. The first operation was a femoro
      anterior tibial bypass using an autogenous saphenous vein to revascularise the
      foot. This was followed by debridement and attachment of a free subscapular flap
      to cover the defect 2 weeks later by a plastic surgeon. After 85 days of
      rehabilitation by physiotherapy and education of foot care by a podiatrist, the
      patient was discharged home and was able to walk with a walking-stick. This
      multidisciplinary approach

PMID- 11830695
TI  - Should we perform early operations in children who have reducible inguinal
      hernia?

PMID- 11830694
TI  - Sarcoidosis in a Hong Kong Chinese woman.
AB  - Sarcoidosis is rare in the Chinese population and most patients with sarcoidosis
      present with asymptomatic mediastinal lymphadenopathy. We report on a 31-year-old
      woman who presented with bilateral hilar lymphadenopathy and pulmonary
      infiltration that spontaneously resolved without treatment, and we present a
      review of the literature on sarcoidosis among the Hong Kong Chinese population.

PMID- 11830696
TI  - Public health issues---aspects of health promotion.

PMID- 11830697
TI  - Current practice in preventing blood---borne diseases during organ/tissue
      transplantation in Hong Kong Scientific Committee of the Advisory Council on AIDS
      and the Hong Kong Society of Transplantation, 5/F Yaumatei Jockey Club Clinic,
      145 Battery Street, Yaumatei, Kowloon, Hong Kong.
AB  - A questionnaire survey was conducted in late September 1996 to study the current
      practice in preventing blood-borne diseases during organ/tissue transplantation
      at local institutions. Twenty-five (83%) of 30 public transplantation
      institutions responded. Kidney and cornea/sclera transplantations were the most
      commonly practised procedures. Some institutions performed bone, skin, liver,
      heart and lung, and bone marrow transplantations. A variety of measures have been
      taken by most of the institutions to uphold safety during transplantation.
      Nevertheless, a lack of protocol standardisation and inadequate awareness to
      communicable diseases during transplantation are apparent. The establishment of
      local guidelines and the implementation of an effective monitoring mechanism
      might minimise the transmission risk of communicable diseases that are associated
      with transplantation.

PMID- 11830698
TI  - Effectiveness of non-mydriatic retinal photography and direct ophthalmoscopy in
      detecting diabetic retinopathy.
AB  - This is a prospective study to compare the effectiveness of non-mydriatic
      photography with that of direct ophthalmoscopy in screening for diabetic
      retinopathy in 153 patients attending a hospital clinic in Hong Kong. Retinal
      photography under physiological mydriasis and direct ophthalmoscopy of patients
      with dilated pupils were compared with the ophthalmologists' examination results
      as a reference standard. The prevalence of diabetic retinopathy in this sample
      population was 15%. The sensitivity of detecting diabetic retinopathy by retinal
      photography was higher than that of direct ophthalmoscopy (64% versus 41%; 95%
      confidence interval of difference, 1.2%- 44.3%). Of five patients who had serious
      retinopathy, retinal photography failed to detect the disease in two; direct
      ophthalmoscopy failed to detect the disease in all five patients. Specificities
      of retinal photography and direct ophthalmoscopy were 90% (95% confidence
      interval, 84%-96%) and 93% (95% confidence interval, 88%-97%), respectively. We
      conclude that retinal photography is significantly more effective than direct
      ophthalmoscopy in detecting diabetic retinopathy. In addition, the non-mydriatic
      camera is easy to use and is the preferred method of screening.

PMID- 11830699
TI  - Epidemiology of severe childhood eye injuries that required hospitalisation.
AB  - We conducted a retrospective study of all paediatric ocular injuries that were
      treated at the Prince of Wales Hospital between October 1991 and January 1997. Of
      the 60 injuries reviewed, eight (13.3%) resulted in some degree of visual
      deficit. The mean age was 5.5 years and the average male to female ratio was
      2.75:1. The distribution of injuries was as follows: contusions, 29 (48.3%); non
      penetrating lacerations, 14 (23.3%); penetrating lacerations, six (10.0%);
      chemical burns, six (10%) and superficial foreign bodies, five (8.3%). Thirteen
      (21.7%) ocular injuries were associated with common household items, seven
      (11.7%) injuries were due to toy gun pellets, and five (8.3%) injuries were
      sports-related. A total of 28 operations were performed on 21 patients, and the
      mean duration of hospital stay was 3.6 days. The visual outcome depended mainly
      on the type and severity of the injury. Some childhood eye injuries are
      preventable by means of more public education, improved safety measures, and
      closer adult supervision.

PMID- 11830700
TI  - Translation and calibration of a Chinese version of the Sickness Impact Profile
      for use in Hong Kong.
AB  - Because of the lack of suitable generic health status measures in Hong Kong that
      reflect the value structure and culture of the society, we have translated and
      calibrated the Sickness Impact Profile, which was originally developed in the
      United States. Translation consisted of a sequence of forward translations into
      Chinese, back translations into English and, when there was a loss of meaning or
      conceptual equivalence, retranslation into Chinese. Sixty Hong Kong Chinese
      people, including health professionals, patients, and members of the public were
      then recruited to determine item and dimension weights for the Hong Kong
      population. Individual ratings were averaged to obtain a consensus value for each
      item. Within-category reliability analysis for scores varied from 0.70 to 0.92
      (Cronbach's alpha values) and overall internal consistency was 0.98. There were
      only small differences between this version and the original American English
      version in the ratings given to individual questions (Pearson's product moment
      correlation coefficient, r=0.8). We have developed a Chinese translation of the
      Sickness Impact Profile, which can now be used to evaluate health outcomes in
      Hong Kong and to compare outcomes with studies in other populations where the
      Sickness Impact Profile was used.

PMID- 11830701
TI  - Nutrition and health issues in the general Hong Kong population.
AB  - In Hong Kong, the chronic diseases that lead to mortality and morbidity, and
      contribute to disability include cardiovascular diseases, cancer, hypertension,
      osteoporosis, and diabetes mellitus. The role of nutrition as a risk factor for
      the development of these diseases has been described elsewhere. For the older
      population, adequate nutrition is important to maintain health, particularly with
      regard to the effect of nutrition on immunocompetence. Nutritional surveys of the
      general adult population show that although the intake pattern for cardiovascular
      health is good, follow-up surveys to monitor the pattern are needed. In the
      context of chronic disease prevention, decreasing salt consumption, increasing
      calcium intake, and increasing the awareness of the health value of fibre may all
      be beneficial actions. Educational efforts should be directed particularly at
      those with lower levels of education, since the poorly educated have been shown
      to have a less healthy diet and a greater prevalence of overweight individuals.
      Among the elderly, evidence of undernutrition has been documented in
      institutional settings and is associated with increased mortality. The diet of
      those residing in vegetarian homes has been shown to be deficient in many B
      vitamins, which results in a high frequency of nutritional anaemias. To help
      achieve an optimal nutritional status, nutrition screening programmes should
      become an integral part of the development of quality care programmes for
      institutions responsible for care of the elderly.

PMID- 11830702
TI  - Exercise and health---new imperatives for public health policy in Hong Kong.
AB  - Physical inactivity is an important and largely avoidable cause of incapacity.
      Regular physical activity protects against several chronic diseases, including
      cardiovascular disease---one of the major causes of death in Hong Kong.
      Significant benefits can be achieved by regular participation in moderate amounts
      of either recreational or general lifestyle physical activities. Even more is
      gained from increasing the frequency, duration, and vigour of exercise. In Hong
      Kong, 59% of all adults lead a fairly sedentary lifestyle and only one in three
      exercise at levels that are thought to offer significant health benefits. An even
      more disturbing fact is that Hong Kong probably has the most inactive primary
      level schoolchildren in the world. The prevalence of these risk behaviours should
      make schoolchildren a priority for any public health prevention programme.

PMID- 11830703
TI  - Osteoporosis---is it really preventable? 
AB  - Osteoporosis is a major public health problem in Hong Kong. For instance, in
      1995, a total of 3783 hip fractures occurred, with an associated acute care cost
      of HK$150 million. Thirty percent of elderly women in Hong Kong are known to have
      one or more vertebral fractures. The main risk factors for osteoporotic fracture
      in the Hong Kong Chinese population include a low dietary calcium intake, an
      inactive lifestyle, smoking, and frequent falls. Prevention for high-risk
      individuals involves the bone mineral density measurement followed by drug
      treatment. In a population-based approach, the entire population is targeted for
      the removal of risk factors. Osteoporosis in Hong Kong is potentially
      preventable, provided that the medical profession and the public can be motivated
      to participate, and adequate resources allocated for its prevention and
      treatment.

PMID- 11830704
TI  - Childhood injury prevention in Hong Kong Hong Kong Childhood Injury Prevention
      Research Group.
AB  - Injury is a major health problem in Hong Kong children. During the past two
      decades, injury and poisoning have surpassed infectious diseases as the leading
      cause of childhood mortality in Hong Kong. These two are also the leading cause
      of childhood disability. In 1995, injury and poisoning caused approximately 2% of
      the deaths among children aged 0 to 1 years, 26% of the deaths among children
      aged 1 to 4 years, and 36% of all deaths of children aged 4 to 14 years. Road
      traffic accidents, drowning and submersion, and accidental falls accounted for
      30%, 20%, and 20%, respectively, of all deaths from unintentional injury in
      children younger than 15 years of age. Exact morbidity figures for injury and
      poisoning are not available but injuries are known to account for approximately
      30% of paediatric attendances at the accident and emergency departments of
      regional hospitals, 20% of all hospitalisations among children, and 65% of
      surgical or orthopaedic admissions. It has been estimated that approximately 2.9%
      of children will be admitted to hospital for an injury at least once before their
      fourth birthday. Hong Kong is a small, highly urbanised, and densely populated
      place that has undergone tremendous socio-economic development in the past three
      decades. The pattern of injuries has changed and shows some special
      characteristics. Information on the extent of the problem, the type of injury,
      and contributing factors are scarce. Preventive measures are reactive in nature,
      piecemeal, and usually not subject to evaluation. It is recommended that
      childhood injury prevention be accorded a high priority, child safety be given
      prime consideration in all policies involving children, and more research be
      conducted.

PMID- 11830705
TI  - The public health harm of tobacco and its prevention in Hong Kong.
AB  - This paper briefly reviews the health hazards associated with smoking, including
      passive smoking, with specific reference to local (Hong Kong) evidence. A Medline
      search of Hong Kong papers from January 1966 to January 1998 was made, and these
      and other relevant papers were reviewed. In Hong Kong, at least 10 people die
      daily from smoking- related diseases. Local studies show that smoking is
      associated with lung cancer, oesophageal cancer, liver cancer, ischaemic heart
      disease, peripheral vascular disease, ischaemic stroke, peptic ulcer,
      osteoporosis, impaired lung function, respiratory symptoms, and other adverse
      health effects. Smoking in pregnant women can result in smaller babies being
      born. Pooled results from four case-control studies show a 60% excess risk of
      lung cancer due to exposure to environmental tobacco smoke. Several studies
      confirm the link between exposure to environmental tobacco smoke and respiratory
      illness, hospitalisation, and asthma in children. The risks of smoking (one of
      every two smokers will be killed by tobacco) are not well known and are
      underestimated by both doctors and the public. Stronger health messages and more
      local evidence are needed to support tobacco control in Hong Kong.

PMID- 11830706
TI  - The politics of tobacco.
AB  - Smoking prevalence and tobacco-attributable mortality will increase substantially
      in the Asia- Pacific region well into the next century, due to population
      expansion, ageing populations, and the fact that more women are smoking. The
      economic costs of tobacco, already substantial, will rise. Of particular concern
      is the penetration of the region by the transnational tobacco companies, which
      deny the health evidence of the harm from tobacco, use sophisticated promotions,
      and lobby to oppose tobacco control measures. There is an urgent need for robust
      tobacco control action to be taken by every country, but many governments have
      little experience in combatting this new epidemic or in countering the tobacco
      companies. They are needlessly concerned that tobacco control action will harm
      their economy, leading to loss of tax revenue and jobs. Arguments to convince
      governments must be shaped to address economic issues and illustrate that such
      action is not only good for a nation's health, but also good for its economy.

PMID- 11830707
TI  - Aspirin---the novel antiplatelet drug.
AB  - Aspirin is a non-steroidal anti-inflammatory drug that has potent antiplatelet
      actions. Aspirin was initially used as an analgesic and antipyretic drug before
      its anti-inflammatory properties were discovered. Aspirin also has antithrombotic
      effects due to the inhibition of cyclo- oxygenase activity in platelets, which
      reduces the extent of thromboxane A2 formation and consequently the aggregability
      of platelets. Prophylactic low-dose aspirin therapy reduces the risk of future
      cardiovascular events in a variety of clinical settings. The maximum effect of
      aspirin in reducing risks of myocardial infarction is achieved soon after the
      initiation of therapy. The selective inhibition of platelet thromboxane A2 may be
      the pharmacological basis for the effectiveness of aspirin in treating pregnancy
      induced hypertension. Aspirin can virtually abolish thromboxane A2 production in
      patients receiving fish oil. Thus, aspirin has been and will be the standard
      reference compound for long-term oral treatment of platelet hyperactivity, most
      notably in the secondary prevention of myocardial infarction.

PMID- 11830708
TI  - The prevention of communicable diseases in Hong Kong.
AB  - Some of the recent communicable disease problems in Hong Kong are summarised to
      illustrate the strengths and weaknesses of how Hong Kong currently controls and
      prevents communicable diseases. Suggestions on how Hong Kong could improve the
      control and prevention of communicable diseases are made.

PMID- 11830709
TI  - Clinical management guidelines for osteoporosis in Hong Kong The working group
      for formulating clinical management guidelines for osteoporosis in Hong Kong.
AB  - The following guidelines provide a basis for the management of osteoporosis for
      the practising physician in Hong Kong. The guidelines have been compiled by a
      working group that represents the specialties concerned with osteoporosis and
      summarise the current management of osteoporosis based on available published
      evidence and relevant local experience.

PMID- 11830710
TI  - Gastro-intestinal cytomegalovirus infection and extensive colonic ulceration in a
      renal transplant recipient.
AB  - Cytomegalic inclusion disease is a common complication in recipients of organ
      transplants. In renal transplant recipients, the disease involves the lungs more
      often than it does the gastrointestinal tract. We report on a recipient of a
      cadaveric kidney who had cytomegalic inclusion disease that involved both the
      upper and lower gastro-intestinal tract, and massive gastro-intestinal bleeding
      that was caused by a large colonic ulcer. Despite treatment with ganciclovir and
      cytomegalovirus-specific immunoglobulin, the patient died from subsequent
      complications.

PMID- 11830711
TI  - Ulcerative colitis exacerbation associated with cytomegalovirus infection.
AB  - There is an increasing prevalence of ulcerative colitis in Hong Kong and
      cytomegalovirus infection is an important factor in the exacerbation of the
      disease. We report on a 33- year-old Chinese man with ulcerative colitis in
      remission, who presented with bloody diarrhoea that failed to respond to an
      intensive regimen of oral and rectal steroid. Colonoscopy was performed and
      biopsy specimens showed signs of cytomegalic colitis in association with
      ulcerative colitis. Administration of ganciclovir and the gradual termination of
      steroid treatment resulted in remission of the colitis. The clinical course
      suggested an exacerbation of ulcerative colitis due to cytomegalovirus infection.
      The relationship between ulcerative colitis and cytomegalovirus is discussed.

PMID- 11830712
TI  - [Echocardiographic evaluation of coronary flow reserve in patients with essential
      hypertension].
AB  - BACKGROUND: In patients with essential arterial hypertension (EAH) the left heart
      ventricular hypertrophy (LVH) causes structural and functional alterations of the
      coronary vessels that can alter the coronary blood flow reserve. The aim of this
      study is to evaluate in hypertensive patients with or without LVH versus
      normotensive subjects, the blood flow and the coronary vasodilatation capability
      and the coronary blood flow reserve in basal conditions and during dipiridamole
      i.v. infusion. METHODS: Eighty patients have been selected by ECG, echo color
      Doppler, transesophageal echocardiography: 50 were hypertensive patients with and
      without LVH, from mild to moderate to severe and 30 were normotensive subjects.
      The enrolled patients underwent a first transesophageal echocardiography, before
      and during infusion of 0.86 mg/kg of dipiridamole in growing doses, 0.56 in four
      minutes followed after three minutes by 0.30 mg/kg. The observation lasted 18
      months, and no patients left the study. RESULTS: The coronary resistances in
      hypertensive patients were significintally reduced during dipiridamole infusion,
      maintaining their level higher compared to the normal controls. The reduced
      coronary vasodilatation capability in hypertensive subjects could be due to an
      increase of the basal vessel tone and/or a reduced compliance of the coronary
      resistances. The coronary blood flow reserve is significantly reduced in all
      hypertensive studied, included those without LVH. It is suggested that this is
      secondary to increase of the coronary blood flow and tone. CONCLUSIONS: In
      conclusion essential arterial hypertension is the cause of early anatomical and
      functional coronary alterations leading hypertensive subjects to risk for
      coronary events before LVH.

PMID- 11830713
TI  - A 2D Echo color-Doppler study of the extracranial carotid arteries in borderline
      arterial isolated systolic hypertension.
AB  - BACKGROUND: The aim of this study was to evaluate the prevalence of
      atherosclerotic carotid lesions in isolated systolic borderline arterial
      hypertension by 2D echo color-Doppler and effect of night-time pressure fall by
      ambulatory blood pressure monitoring. METHODS: Outpatients from January 1992 to
      December 1998 were examined. One hundred and twenty normotensive control subjects
      and 99 isolated systolic borderline untreated hypertensives were studied, based
      on blood pressure fall were divided into dippers, with nocturnal systolic and/or
      diastolic blood pressure fall of >10%, and non dippers. Subjects with ischemic
      heart disease, valvulopathies, heart failure, renal insufficiency,
      cerebrovasculopathies, hypercholesterolemia (total cholesterol >200 mg/dl) and
      diabetes. Normotensives and hypertensives were homogenous for cardiovascular risk
      factors. A thickness of =/> 0.95 mm, calculated as a mean of 5 measurements of
      the common carotid artery, 2-3 cm from the carotid bifurcation, was considered a
      sign of myointimal thickening, and the plaque as a focal thickening of =/> 2 mm,
      based on echogenic characteristics and site. RESULTS: Compared to normotensives,
      isolated systolic borderline hypertensives, showed carotid arteries with an
      intima-media thickening (p=0.002) with one or more plaques (p=0.0001) much more
      frequently, while normal carotid arteries (p=0.0001) were less frequent. In
      normotensives, like in hypertensives, the prevalence of vasal lesions was not
      significantly different in dippers compared with non dippers. Plaques were most
      often localized at level of the common carotid and lesions were hard.
      CONCLUSIONS: The conclusions is drawn that isolated systolic hypertension is the
      sign of major vascular atherosclerotic lesions. The night-time pressure fall does
      not affect the importance of the lesions.

PMID- 11830714
TI  - [Bilateral and monolateral dolichoarteriopathies (Kinking, Coiling, Tortuosity)
      of the carotid arteries and atherosclerotic disease. An ultrasonographic study].
AB  - BACKGROUND: The aim of this study, performed in outpatients, is to evaluate,
      using echo color Doppler examination, atherosclerotic lesions of extracranial
      carotid arteries in subjects with bilateral, and monolateral
      dolichoarteriopathies. METHODS: A total of 316 subjects, 77 with bilateral and
      239 with monolateral dolichoarteriopathies, were studied. Patients were divided
      into: 79 subjects without cardiovascular risk factors and 237 subjects with
      cardiovascular risk factors (98 with arterial hypertension alone, 85 with
      arterial hypertension associated with other cardiovascular risk factors, 54 with
      hypercholesterolemia, diabetes, cigarette smoking, alone or associated).
      Myointimal thickness, as a mean of 5 measurements at common carotid level, 2-3 cm
      from flow-divider and plaques as a focal thickness =/> 2 mm, were evaluated.
      RESULTS: In 77 patients with bilateral dolichoarteriopathies, compared to 239
      patients with monolateral dolichoarteriopathies, there were no differences in
      myointimal thickening, and in the prevalence of carotid plaques; no difference
      was observed between sexes. Both in subjects with and without cardiovascular risk
      factors myointimal thickness and carotid plaques didn't show any significant
      differences in bilateral compared with monolateral dolichoarteriopathies.
      CONCLUSIONS: In conclusion, bilateral, compared with monolateral,
      dolichoarteriopathies of the carotids, do not seem to be a consequence of
      atherosclerotic lesions.

PMID- 11830715
TI  - [Indications and short term results of subfascial endoscopic perforator surgery
      (SEPS)].
AB  - BACKGROUND: The aim of this study is to evaluate diagnostic methods, indications
      and surgical technique in SEPS procedure and to analyze short term results.
      METHODS: Eighteen patients affected by chronic venous insufficiency (CVI) have
      been analyzed. According to NAVS (North American Vascular Society) classification
      three patients were included in class 6 (C6), 3 (C5), 6 (C4), 2 (C3) and 4 (C2).
      From 2 to 5 selective subfascial endoscopic ligation of perforator veins,
      especially I and II Cockett perforator veins' were performed. In 7 cases, total
      stripping of the great (6) or less (1) saphenous vein was associated with SEPS
      procedure. After the operation, an elastic bandage of the lower limbs was
      performed and a medical treatment with LMVH was started. RESULTS: In 6 patients
      of the C2 and C3 groups, neither recurrence or pathological reflux were observed
      at clinical examination and at color duplex. In 12 patients of C4, C5 and C6
      groups a reduction of the perimalleolar oedema was observed. In the last 3
      patients, with leg ulceration, a resolution of the lesion in 2 cases, and a
      reduction in diameter in the last one, were observed. CONCLUSIONS: SEPS is
      particularly advised in those patients belonging to C5 and C6 groups, especially
      in presence of leg ulceration. This operations is suggested also in patients with
      CVI and incontinence of perforator veins detected by at color duplex. This
      diagnostic investigation seems to be adequate in the diagnosis of CVI and in the
      mapping of perforator veins of the leg.

PMID- 11830716
TI  - [Telangiectasias associated with reticular veins. Sclerotherapy or combined
      sclerotherapeutic and surgical approach?].
AB  - BACKGROUND: We compare the results obtained with sclerotherapy or combined
      surgical and sclerotherapic approach in two groups of patients, affected by
      reticular veins-related telangiectasias without incompetence of the saphenous
      systems or perforating veins. METHODS: 44 female patients were evaluated at our
      Institution. The first group (21 patients) was treated with sclerotherapy
      (polidocanol at a concentration of 1% for the reticular veins and 0.25% for the
      telangiectasias); the second group (23 patients) was treated with a combined
      approach (ambulatory phlebectomy according to Muller and sclerosis using
      polidocanol at a concentration of 0.25%). Six and twelve months after surgery or
      sclerotherapy, we evaluated the appearance of hyperpigmentation or telangiectatic
      matting, and the recurrence of the treated vessels. RESULTS: In the first group,
      the hyperpigmentations and the appearance of telangiectatic matting showed, after
      6 months, an incidence rate of 14.3% after 12 months, a recurrence of the treated
      vessels was observed in 4 patients (19%). In the second group, the
      hyperpigmentations and the appearance of telangiectatic matting showed, after 6
      months, an incidence rate of 4.3% at 12 month follow-up no recurrence of treated
      vessels was observed. CONCLUSIONS: The combined approach might be considered, in
      selected patients, a valid alternative to sclerotherapy in the treatment of
      reticular veins-related telangiectasias, particularly in preventing side effects
      such as hyperpigmentations and telangiectatic matting.

PMID- 11830717
TI  - [Popliteal aneurysms. Personal experience].
AB  - BACKGROUND: The 70% of peripheral aneurysms are localized at the popliteal
      artery; approximately one third of patients are asymptomatic, but the occurrence
      of complications (acute ischemia, rupture) endangers the survival of the leg. The
      purpose of this paper is to demonstrate the validity of elective surgery for
      popliteal aneurysms, also for asymptomatic lesions. METHODS: Twenty-seven
      popliteal aneurysms were observed in 20 patients; only 7 of these were affected
      by a unilateral lesion, other 7 patients by a bilateral lesion and the remainder
      6 patients by a polydistrict association; 3 patients refused the surgical therapy
      which was proposed. Prosthetic grafting with exclusion or resection of the
      aneurysm has been practiced in 16 cases; one time only a Dacron graft was
      employed, while the autologous saphenous vein was employed in 15 cases. A
      locoregional thrombolysis has been performed in 3 patients, in presence of an
      acute peripheral ischemia. In 5 cases a conservative approach has been chosen;
      these were asymptomatic aneurysms with a <2 cm diameter. RESULTS: In 87,5% of
      patients operated (14/16) a good immediate result was obtained. In a mean 2 years
      follow-up the 75% of these patients maintained the clinical result. The
      fibrinolytic therapy was resolutive in 2 cases of acute peripheral ischemia; a
      lumbar sympathectomy was necessary in one case. CONCLUSIONS: In consideration of
      the complications that the aneurysmatic disease can give, among which the acute
      peripheral ischemia is the most dreadful, a surgical approach is widely
      justified, also in the light of the good results described.

PMID- 11830718
TI  - Anticoagulation for cardioversion of atrial fibrillation.
AB  - The cardioversion of chronic atrial fibrillation to sinus rhythm carries a
      thromboembolic risk of 1.5-6%. These events occasionally occur at the time of
      cardioversion, but more often happen hours or days later. These strokes and other
      embolic events may occur even where atrial thrombus has been excluded before
      cardioversion and it has become apparent that, although atrial electrical
      activity may be restored by cardioversion, normal mechanical atrial function may
      take longer to recover. Numerous studies have addressed the role of
      anticoagulation following cardioversion in patients with atrial fibrillation,
      however, the mechanism of embolic complications as well as the justification of a
      standard anticoagulation therapy are not fully established. In this review we
      will try to present an overview of the mechanisms of thrombosis following
      cardioversion and give an insight into current anticoagulation strategies.

PMID- 11830719
TI  - Aortic atheroma. An unknown source of ischemic stroke.
AB  - Cerebrovascular mortality represents 25% of all cardiovascular mortality.
      Defining the pathological mechanism of an episode of ischemic stroke is important
      for epidemiological, prognostic and overall therapeutic purposes. About 1/4 of
      ischemic strokes are defined as being of unknown cause. The use of
      transesophageal echocardiography for studying the aortic arch and thoracic aorta,
      revealed that aortic atheroma can be considered as an embolic source.
      Retrospective studies documented a significant prevalence of atheroma >4 mm in
      the aortic arch in patients with previous stroke (15%); while prospective studies
      documented an increased risk for cardiovascular events in patients with plaque of
      =/> 4 mm in thickness at the level of the thoracic aorta compared with controls
      without these lesions: in particular, the incidence of recurrent stroke is
      12%/year, while the incidence of cardiovascular events is 26%. Plaques defined
      unstable and at risk of embolic event are protrudent, >4 mm in thickness, without
      calcification and have on their surface mobile thrombus. Embolization from a
      protrudent atheroma can have a iatrogenic cause, that is cardiac catheterization
      or placement of an intra-aortic balloon- pump or during cardiopulmonary bypass.
      The management of the subject with aortic atheroma is not well defined.
      Encouraging dates with the use of statins are from a recent meta-analysis also
      anticoagulant treatment versus antiplatelet treatment, reduced incidence of
      stroke in a significant manner. The surgical therapy of aortic endoarterectomy,
      has, at this moment, a limited indication, because is not without risk.
      Transesophageal ecocardiography is a method of choice for the study of the aortic
      atheroma and it should be done in every patient with stroke by unknown cause.

PMID- 11830720
TI  - [Statine and endothelium dysfunction in diabetes].
AB  - Diabetes is associated with significant morbidity and mortality in the setting of
      acute coronary syndromes. Exists a progressive relationship between glucose
      levels and cardiovascular risk. Hyperglycemy in fact produces endothelial
      dysfunction recognised to be a key accessory to diabetic microangiopathy and
      macroangiopathy. Furthermore diabetics present high levels of cholesterol which
      elevate the risk of CHD. The statins, for their effects, may represent the fit
      therapy. The beneficial effects of statins may extend beyond improving the lipid
      profile. There are several proposed mechanisms for event reduction by lipid
      lowering therapy, which include improved endothelium-dependent vasodilation,
      stabilization of atherosclerotic lesions, reduction in inflammatory stimuli, and
      prevention, slowed progression, or regression of atherosclerotic lesions
      (pleiotropic effects). Cellular experiments suggest that statins have an impact
      on endothelial function by preventing oxidized LDL-induced reduction of nitric
      oxide production and increased nitric oxide synthesis. Statins also impact
      chronic inflammation by reducing mitogen (PDGF) responsiveness, inhibiting smooth
      muscle cell proliferation, inhibiting monocyte chemotaxis and migration, and by
      reducing macrophage protease production. The absolute clinical benefit achieved
      may be greater in diabetic than in nondiabetic patients with CHD because diabetic
      patients have a higher absolute risk of recurrent CHD events and other
      atherosclerotic events.

PMID- 11830722
TI  - Call to the Nursing Profession: nursing's agenda for the future.

PMID- 11830721
TI  - Endoluminal repair of axillary artery and vein rupture after reduction of
      shoulder dislocation. A case report.
AB  - A case of endoluminal repair of vein and artery axillary rupture after reduction
      of shoulder dislocation in an 83-year-old woman is reported. The lesions were
      repaired successfully with two cover stents (JOSTENT and Passager). Endovascular
      treatment of such vascular injuries seems to be feasible and safe, though further
      investigation is warranted.

PMID- 11830723
TI  - The journal looks forward to your E-mail or call in 2002.

PMID- 11830724
TI  - Follow up on workplace violence case review.

PMID- 11830725
TI  - Routine placement of heparin locks is beneficial.

PMID- 11830726
TI  - Condolences from New Zealand emergency nurses regarding September 11 terrorism.

PMID- 11830727
TI  - A 23-year-old with refractory seizures following an isoniazid overdose.

PMID- 11830728
TI  - The extent, nature, and precipitating factors of nurse assault among three groups
      of registered nurses in a regional medical center.
AB  - INTRODUCTION: This study investigated nurse perceptions of the incidence and
      nature of verbal and physical assault or abuse by patients and their family
      members or visitors. METHODS: A survey was given to ED, ICU, and general floor
      nurses in a 770-bed acute care north Florida medical center. RESULTS: The
      response rate was 68.8% (86 out of 125). Large percentages of nurses reported
      being victims of verbal assault or abuse and physical assault by patients and
      family members or visitors; 88% reported being verbally assaulted and 74%
      reported being physically assaulted while at work in the past year. ED nurses
      reported the highest rates of these incidences, with 100% reporting verbal
      assault and 82.1% reporting physical assault within the past year. Assaults were
      most commonly perpetrated by patients with cognitive dysfunction (79.1%),
      patients with substance abuse (60.5%), and persons who were angry because of the
      patient's condition (55.8%). Surprising information: the most common causes of
      assault by family members and visitors were anger related to enforcement of
      hospital policies (58.1%), anger related to the patient's condition/situation
      (57%), anger related to long wait times (47.7%), and anger related to the health
      care system in general (46.5%). DISCUSSION: Nurses were confused about what
      legally constitutes "assault" and "abuse"; nurse rights versus patient rights;
      and policies and procedures for reporting assault or abuse incidences. Our
      results indicate that nurses are experiencing abusive and assaultive behavior
      from family members and visitors just as often as they are from patients, and ED
      nurses are at higher risk. Nurses perceive a lack of institutional support and an
      institutional emphasis on patient rights and satisfaction and do not feel safe in
      the workplace.

PMID- 11830729
TI  - Efficacy of a 2-year-old sexual assault nurse examiner program in a Canadian
      hospital.
AB  - INTRODUCTION: The purpose of this study was to describe a sexual assault nurse
      examiner (SANE) program at a hospital-based sexual assault care center in
      Ontario, Canada, and assess its efficacy in comparison with physician examiners.
      METHODS: Data obtained from the hospital records of 515 women who came to a
      Toronto sexual assault care center were examined. A number of variables relevant
      to this assessment of services were examined, including client demographics and
      presenting history, aspects of the sexual assault, and characteristics of the
      treatment. RESULTS: Average assessment times were shorter for victims seen by
      SANEs than for victims seen by physicians (approximately 3(1/4) hours versus 4
      hours). Physicians had more interruptions (25.1%) than did SANEs (20.0%). Client
      characteristics and presentation were similar regardless of who provided care,
      with some exceptions. DISCUSSION: The results of the study support the utility of
      the SANE model as an efficient program for the assessment and treatment of
      victims of sexual assault.

PMID- 11830730
TI  - Guiding principles at triage: advice for new triage nurses.

PMID- 11830732
TI  - A newly revised nursing ED documentation form for a level I trauma center.

PMID- 11830733
TI  - Nurse staffing levels in American hospitals: a 2001 report.

PMID- 11830734
TI  - An informal discussion of emergency nurses' current clinical practice: what's new
      and what works.

PMID- 11830735
TI  - "To err is human..." patient safety initiatives for EMS.

PMID- 11830737
TI  - Child passenger protection: then and now.

PMID- 11830738
TI  - CMS clarifies application of EMTALA to off-site outpatient departments and to
      hospital campuses.

PMID- 11830740
TI  - Assessing competency: The Broselow-Luten resuscitation tape.

PMID- 11830741
TI  - Role of "nurse coordinator for pediatric emergency care": important part of new
      consensus guidelines.

PMID- 11830742
TI  - Nurses' name badge identification: how Montana's State Board of Nursing has
      decided the issue.

PMID- 11830743
TI  - ED nurse expert witness...for the plaintiff.

PMID- 11830744
TI  - Clients' experiences with a specialized sexual assault service.
AB  - INTRODUCTION: Specialized services have been developed to meet the unique needs
      of survivors of sexual assault, and yet little research has been conducted to
      investigate clients' experiences with these services. An interpretive study was
      conducted to (1) understand the experience of women who were sexually assaulted
      and then cared for in an emergency setting by professionals associated with a
      specialized sexual assault service; (2) discover themes in the experiences of
      these women; and (3) discern implications of this experience for delivery of care
      to women who have been sexually assaulted. METHODS: Eight women who had been
      cared for at a specialized sexual assault service were interviewed 2 months
      later. RESULTS: Nine themes emerged from latent content analysis of the
      interviews. DISCUSSION: Conclusions drawn include the importance of holistic
      woman-centered care, the importance of having one caregiver focus on the client's
      emotional needs, the importance of touch, and the need for an effective,
      sensitive, and coordinated response by police and community services.

PMID- 11830745
TI  - Medically impaired drivers: is there a place for ED staff reporting?

PMID- 11830746
TI  - This morning.

PMID- 11830748
TI  - AH-1058: a novel cardioselective Ca2+ channel blocker.
AB  - The pharmacologic profile of a cyproheptadine-related compound, 4-(5H
      dibenzo[a,d]cyclohepten-5-ylidene)-1-[(E)-3-(3-methoxy-2-nitro)phenyl-2
      propenyl]piperidine hydrochloride (AH-1058), was assessed in various in vivo and
      in vitro models. In guinea pig cardiomyocytes, AH-1058 effectively suppressed L
      type Ca2+ channel currents without affecting other ion channel or ion exchange
      currents. In rat cerebral cortical membranes AH-1058 appears to bind
      preferentially to L-type Ca2+ channels at phenylalkylamine- and benzothiazepine
      binding sites. In canine isolated, blood-perfused heart preparations, AH-1058
      exerted negative inotropic, dromotropic, and chronotropic and weak coronary
      vasodilator effects. In halothane-anesthetized dogs, AH-1058 suppressed
      ventricular contractility and decreased blood pressure and cardiac output. Total
      peripheral vascular resistance was hardly affected by the drug, suggesting that
      in vivo AH-1058 can selectively suppress cardiac, as compared to peripheral
      vascular, function. In conscious dogs, by intravenous administration AH-1058
      reduced systolic blood pressure and maximal upstroke velocity of the left
      ventricular pressure, while it increased heart rate in a dose-dependent manner.
      The drug did not affect diastolic blood pressure, which is quite different from
      cardiovascular properties of well-known Ca2+ channel blockers, verapamil and
      diltiazem. This unique cardiovascular profile of AH-1058 is expected to be useful
      in the treatment of certain pathological processes such as the obstructive
      hypertrophic cardiomyopathy, vasovagal syncope, dissecting aortic aneurysm, and
      ventricular arrhythmias, in which selective inhibition of the ventricular Ca2+
      channels is essential for drug therapy.

PMID- 11830749
TI  - A review of HNS-32: a novel azulene-1-carboxamidine derivative with multiple
      cardiovascular protective actions.
AB  - HNS-32 [N(1),N(1)-dimethyl-N(2)-(2-pyridylmethyl)-5-isopropyl-3,8-dimethylazulene
      1- carboxamidine] (CAS Registry Number: 186086-10-2) is a newly synthesized
      azulene derivative. Computer simulation showed that its three dimensional
      structure is similar to that of the class Ib antiarrhythmic drugs, e.g.,
      lidocaine or mexiletine. HNS-32 potently suppressed ventricular arrhythmias
      induced by ischemia due to coronary ligation and/or ischemia-reperfusion in dogs
      and rats. In the isolated dog and guinea pig cardiac tissues, HNS-32 had negative
      inotropic and chronotropic actions, prolonged atrial-His and His-ventricular
      conduction time and increased coronary blood flow. In the isolated guinea pig
      ventricular papillary muscle, HNS-32 decreased maximal rate of action potential
      upstroke (Vmax) and shortened action potential duration (APD). These findings
      suggest that HNS-32 inhibits inward Na+ and Ca2+ channel currents. In the
      isolated pig coronary and rabbit conduit arteries, HNS-32 inhibited both Ca2+
      channel-dependent and -independent contractions induced by a wide variety of
      chemical stimuli. HNS-32 is a potent inhibitor of protein kinase C (PKC)-mediated
      constriction of cerebral arteries. It is likely to block both, Na+ and Ca2+
      channels expressed in cardiac and vascular smooth muscles. These multiple ion
      channel blocking effects are largely responsible for the antiarrhythmic and
      vasorelaxant actions of HNS-32. This drug may represent a novel approach to the
      treatment of arrhythmias.

PMID- 11830750
TI  - Cardiovascular properties of yangambin, a lignan isolated from Brazilian plants.
AB  - Yangambin was initially selected from a number of lignans isolated from Brazilian
      plants for its ability to antagonize Platelet-Activating Factor (PAF, 1-O
      hexadecyl-2-acetyl- sn-glyceryl-3-phosphorylcholine)-induced biological effects.
      Subsequently it was shown that, besides its antagonistic properties at PAF
      receptors, yangambin also prevents the cardiovascular collapse observed during
      anaphylactic and endotoxic/septic shocks, as well as the vascular and cardiac
      hyporesponsiveness to catecholamines in endotoxic shock. It is suggested that
      this naturally occurring compound could be of potential interest in the
      adjunctive management of the above mentioned pathologies. In the present article,
      we review the main studies investigating the pharmacological properties of
      yangambin related to the cardiovascular function.

PMID- 11830751
TI  - Transforming growth factor-beta: a promising target for anti-stenosis therapy.
AB  - Transforming growth factor-beta (TGF-beta) is the general name for a family of
      cytokines which have widespread effects on many aspects of growth and
      development. The TGF-beta isoforms are produced by most cell types and exert a
      wide range of effects in a context-dependent autocrine, paracrine or endocrine
      fashion via interactions with distinct receptors on the cell surface. TGF-beta is
      involved in the wound healing process and, thus plays a significant role in the
      formation of a restenotic lesion after percutaneous transluminal coronary
      angioplasty (PTCA) or stenting. Perhaps because of its wide-ranging effects, TGF
      beta is usually released from cells in a latent form, and its activation and
      signaling are complex. Manipulation of the TGF-beta1, TGF-beta2, and TGF-beta3
      isoforms by inhibiting their expression, activation, or signaling reduces
      scarring and fibrosis in animal models. However, to date, few have reached
      clinical trial. This review summarizes current knowledge on the activation and
      signaling of TGF-beta, and focuses on the anti-TGF-beta strategies which may lead
      to clinical applications in the prevention of restenosis following PTCA or
      stenting.

PMID- 11830752
TI  - Pharmacology of SCH00013: a novel Ca2+ sensitizer.
AB  - Cardiotonic agents that facilitate cardiac pump function by direct improvement of
      contractile dysfunction are indispensable for the treatment of hemodynamic
      disorders in acute myocardial failure and the aggravating phase of congestive
      heart failure. Cardiotonic agents currently available for the treatment of
      hemodynamic crisis in congestive heart failure are catecholamines, selective
      phosphodiesterase (PDE) III inhibitors and digitalis, all of which are Ca2+
      mobilizers. Considering the number of serious adverse effects of these clinically
      available cardiotonic agents, development of agents that act via a novel
      mechanism of action may contribute to the progress of pharmacotherapy of
      congestive heart failure. Ca2+ sensitizers that act by increasing in myofilament
      Ca2+ sensitivity may be able to overcome the disadvantage of Ca2+ mobilizers.
      Ca2+ sensitizers do not increase activation energy, do not produce Ca2+ overload
      and may be effective even under pathophysiological states such as acidosis,
      myocardial stunning and heart failure. SCH00013 ((4,5-dihydro-6-[1-[2-hydroxy-2
      (4-cyanophenyl)ethyl]-1,2,5,6-tetrahydropyrido-4-yl]pyridazin-3(2H)-one)) is a
      novel Ca2+ sensitizer that elicits a moderate positive inotropic effect without
      significant alteration of Ca2+ transients. SCH00013 does not have a positive
      chronotropic effect and has a weak PDE III inhibitory action and class III
      antiarrhythmic action. SCH00013 prolonged the survival in a animal heart failure
      model with genetic cardiomyopathy. The oral bioavailability of SCH00013 is high
      and equivalent to that via intravenous administration. The unique pharmacological
      profiles of SCH00013 imply that this agent may be potentially beneficial for
      pharmacotherapy of contractile dysfunction in congestive heart failure.

PMID- 11830753
TI  - Cilostazol (pletal): a dual inhibitor of cyclic nucleotide phosphodiesterase type
      3 and adenosine uptake.
AB  - Cilostazol (Pletal), a quinolinone derivative, has been approved in the U.S. for
      the treatment of symptoms of intermittent claudication (IC) since 1999 and for
      related indications since 1988 in Japan and other Asian countries. The
      vasodilatory and antiplatelet actions of cilostazol are due mainly to the
      inhibition of phosphodiesterase 3 (PDE3) and subsequent elevation of
      intracellular cAMP levels. Recent preclinical studies have demonstrated that
      cilostazol also possesses the ability to inhibit adenosine uptake, a property
      that may distinguish it from other PDE3 inhibitors, such as milrinone. Elevation
      of interstitial and circulating adenosine levels by cilostazol has been found to
      potentiate the cAMP-elevating effect of PDE3 inhibition in platelets and smooth
      muscle, thereby augmenting antiplatelet and vasodilatory effects of the drug. In
      contrast, elevation of interstitial adenosine by cilostazol in the heart has been
      shown to reduce increases in cAMP caused by the PDE3-inhibitory action of
      cilostazol, thus attenuating the cardiotonic effects. Cilostazol has also been
      reported to inhibit smooth muscle cell proliferation in vitro and has been
      demonstrated in a clinical study to favorably alter plasma lipids: to decrease
      triglyceride and to increase HDL-cholesterol levels. One, or a combination of
      several of these effects may contribute to the clinical benefits and safety of
      this drug in IC and other disease conditions secondary to atherosclerosis. In
      eight double-blind randomized placebo-controlled trials, cilostazol significantly
      increased maximal walking distance, or absolute claudication distance on a
      treadmill. In addition, cilostazol improved quality of life indices as assessed
      by patient questionnaire. One large randomized, double-blinded, placebo
      controlled, multicenter competitor trial demonstrated the superiority of
      cilostazol over pentoxifylline, the only other drug approved for IC. Cilostazol
      has been generally well-tolerated, with the most common adverse events being
      headache, diarrhea, abnormal stools and dizziness. Studies involving off-label
      use of cilostazol for prevention of coronary thrombosis/restenosis and stroke
      recurrence have also recently been reported.

PMID- 11830754
TI  - Donepezil for Alzheimer's disease: pharmacodynamic, pharmacokinetic, and clinical
      profiles.
AB  - Donepezil was developed in order to overcome the disadvantages of physostigmine
      and tacrine. Its use is based on the cholinergic hypothesis. Donepezil is a
      piperidine-based, reversible acetylcholinesterase inhibitor, that is chemically
      unrelated to other cholinesterase inhibitors. It was developed for the
      symptomatic treatment of Alzheimer's disease (AD). Donepezil is highly selective
      for acetylcholinesterase with a significantly lower affinity for
      butyrylcholinesterase, which is present predominantly in the periphery. Phase I
      and II clinical trials demonstrated donepezil's favorable pharmacokinetic,
      pharmacodynamic and safety profile. There is no need to modify the dose of
      donepezil in the elderly or in patients with renal and hepatic failure. Pivotal
      phase-III trials in the US, European countries, and Japan showed that donepezil
      significantly improved cognition and global function in patients with mild to
      moderate AD. In long-term trials, donepezil maintained cognitive and global
      function for up to 1 year prior to the resumption of gradual deterioration.
      Donepezil is generally well tolerated; most of its adverse events are mild,
      transient and cholinergic in nature. Donepezil produces no clinically significant
      changes in laboratory parameters, including liver function. The drug is approved
      for the treatment of mild to moderate Alzheimer's disease, but donepezil therapy
      does not have to be discontinued if a patient continues to deteriorate. Possible
      new indications for donepezil in psychiatric and neurologic diseases, other than
      AD, include dementia with Lewy bodies, brain injury, attention deficit
      hyperactivity, multiple sclerosis, Down's syndrome, delirium, mood disorders,
      Huntington's disease and sleep disorders.

PMID- 11830755
TI  - Eptastigmine: ten years of pharmacology, toxicology, pharmacokinetic, and
      clinical studies.
AB  - Eptastigmine (heptyl-physostigmine tartrate) is a carbamate derivative of
      physostigmine in which the carbamoylmethyl group in position 5 of the side chain
      has been substituted with a carbamoylheptyl group. In vitro and ex vivo results
      suggest that eptastigmine has a long-lasting reversible brain cholinesterase
      (i.e., acetylcholinesterase and butyryl-cholinesterase) inhibitory effect. When
      administered in vivo to rodents by various routes, eptastigmine inhibits cerebral
      acetylcholinesterases (AChE) and increases acetylcholine (Ach) brain levels by
      2500-3000%, depending on the dose. This effect leads to an improvement in the
      cerebral blood flow in the ischemic brain, excitatory and inhibitory effects on
      the gastrointestinal tract and to a protection from acute soman and
      diisopropylfluorophosphate intoxication. Eptastigmine, by either acute or chronic
      administration, has been found to have memory enhancing effects in different
      species of normal, aged and lesioned animals. It also restored to normal the age
      related increase of EEG power without affecting spontaneous motor activity.
      Clinical investigations on more than 1500 patients with Alzheimer's disease
      demonstrated that eptastigmine significantly improved cognitive performance (as
      assessed by the cognitive subscale of the Alzheimer's Disease Assessment Scale)
      as compared with placebo. This improvement was most evident in patients with more
      severe cognitive impairment at the baseline. The relationship between patient
      performance and average steady-state AChE inhibition was described by an inverted
      U-shaped dose-response curve. Pharmacokinetic studies have revealed that after
      oral administration eptastigmine is rapidly distributed to the tissues and
      readily enters the CNS, where it can be expected to inhibit AChE for a prolonged
      period. Eptastigmine is generally well tolerated and the majority of adverse
      events (cholinergic) were mild to moderate in intensity. However, the adverse
      hematologic (granulocytopenia) effects reported in two studies have resulted in
      the suspension of further clinical trials.

PMID- 11830756
TI  - The antidepressant and antiinflammatory effects of rolipram in the central
      nervous system.
AB  - Rolipram is a selective inhibitor of phosphodiesterases (PDE) IV, especially of
      the subtype PDE IVB. These phosphodiesterases are responsible for hydrolysis of
      the cyclic nucleotides cAMP and cGMP, particularly in nerve and immune cells.
      Consequences of rolipram-induced elevation of intracellular cAMP are increased
      synthesis and release of norepinephrine, which enhance central noradrenergic
      transmission, and suppress expression of proinflammatory cytokines and other
      mediators of inflammation. In humans and animals rolipram produces thereby a
      variety of biological effects. These effects include attenuation of endogenous
      depression and inflammation in the central nervous system (CNS), both effects are
      of potential clinical relevance. There are some discrepancies between in vitro
      and in vivo effects of rolipram, as well as between results obtained in animal
      models and clinical studies. The clinical use of rolipram is limited because of
      its behavioral and other side effects. Newly developed selective PDE IV
      inhibitors with presumably higher potency and lower toxicity are currently under
      investigation.

PMID- 11830757
TI  - SCH 23390: the first selective dopamine D1-like receptor antagonist.
AB  - SCH 23390, the halobenzazepine (R)-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl
      2,3,4,5- tetrahydro-1H-3-benzazepine, is a highly potent and selective dopamine
      D1-like receptor antagonist with a K(i) of 0.2 and 0.3 nM for the D1 and D5
      dopamine receptor subtypes, respectively. In vitro, it also binds with high
      affinity to the 5-HT2 and 5-HT1C serotonin receptor subtypes. However, the doses
      required to induce a similar response in vivo are greater than 10-fold higher
      than those required to induce a D1-mediated response. Previous in vivo
      pharmacological studies with SCH 23390 have shown it to abolish generalized
      seizures evoked by the chemoconvulsants: pilocarpine and soman. These studies
      provide evidence of the potential importance of D1-like dopaminergic receptor
      mechanisms in facilitating the initiation and spread of seizures. The inference
      from a majority of studies is that the activation of dopamine D1 receptors
      facilitates seizure activity, whereas activation of D2 receptors may inhibit the
      development of seizures. SCH 23390 has also been used in studies of other
      neurological disorders in which the dopamine system has been implicated, such as
      psychosis and Parkinson's disease. Apart from the study of neurological
      disorders, SCH 23390 has been extensively used as a tool in the topographical
      determination of brain D1 receptors in rodents, nonhuman primates, and humans. In
      summary, SCH 23390 has been a major tool in gaining a better understanding of the
      role of the dopamine system, more specifically the D1 receptor, in neurological
      function and dysfunction.

PMID- 11830758
TI  - Recent developments in the discovery of novel adenosine kinase inhibitors:
      mechanism of action and therapeutic potential.
AB  - Adenosine (ADO) is an endogenous inhibitory neuromodulator that limits cellular
      excitability in response to tissue trauma and inflammation. Adenosine kinase (AK;
      EC 2.7.1.20) is the primary metabolic enzyme regulating intra- and extracellular
      concentrations of ADO. AK inhibitors have been shown to significantly increase
      ADO concentrations at sites of tissue injury and to provide effective
      antinociceptive, antiinflammatory, and anticonvulsant activity in animal models.
      Structurally novel nucleoside and non-nucleoside AK inhibitors that demonstrate
      high specificity for the AK enzyme compared with other ADO metabolic enzymes,
      transporters, and receptors have recently been synthesized. These compounds have
      also demonstrated improved cellular and tissue penetration compared with earlier
      tubercidin analogs. These compounds have been shown to exert beneficial effects
      in animal models of pain, inflammation and epilepsy with reduced cardiovascular
      side effects compared with direct acting ADO receptor (P1) agonists, thus
      supporting the hypothesis that AK inhibitors can enhance the actions of ADO in a
      site- and event-specific fashion.

PMID- 11830760
TI  - Galanin: neurobiologic mechanisms and therapeutic potential for Alzheimer's
      disease.
AB  - The neuropeptide galanin (GAL) is widely distributed in the mammalian CNS.
      Several lines of evidence suggest that GAL may play a critical role in cognitive
      processes such as memory and attention through an inhibitory modulation of
      cholinergic basal forebrain activity. Furthermore, GAL fibers hyperinnervate
      remaining cholinergic basal forebrain neurons in Alzheimer's disease (AD). This
      suggests that GAL activity impacts cholinergic dysfunction in advanced AD.
      Pharmacological and in vitro autoradiographic studies indicate the presence of
      heterogeneous populations of GAL receptor (GALR) sites in the basal forebrain
      which bind GAL with both high and low affinity. Interestingly, we have recently
      observed that GALR binding sites increase in the anterior basal forebrain in late
      stage AD. Three G protein-coupled GALRs have been identified to date that signal
      through a diverse array of effector pathways in vitro, including adenylyl cyclase
      inhibition and phospholipase C activation. The repertoire and distribution of
      GALR expression in the basal forebrain remains unknown, as does the nature of GAL
      and GALR plasticity in the AD basal forebrain. Recently, GAL knockout and
      overexpressing transgenic mice have been generated to facilitate our
      understanding of GAL activity in basal forebrain function. GAL knockout mice
      result in fewer cholinergic basal forebrain neurons and memory deficits. On the
      other hand, mice overexpressing GAL display hyperinnervation of basal forebrain
      and memory deficits. These data highlight the need to explore further the
      putative mechanisms by which GAL signaling might be beneficial or deleterious for
      cholinergic cell survival and activity within basal forebrain. This information
      will be critical to understanding whether pharmacological manipulation of GALRs
      would be effective for the amelioration of cognitive deficits in AD.

PMID- 11830759
TI  - SB-236057-A: a selective 5-HT1B receptor inverse agonist.
AB  - 5-HT1B autoreceptors are involved in the control of extracellular 5-HT levels
      from both the terminal and cell body regions of serotonergic neurons. In this
      manuscript we review the pharmacological and pharmacokinetic data available for
      the selective and potent 5-HT1B receptor inverse agonist, SB-236057-A (1'-ethyl-5
      (2'-methyl-4'-(5-methyl-1,3,4-oxadiazolyl-2-yl)biphenyl-4-carbonyl)-2,3,6,7
      tetrahydrospiro (furo[2,3-f]indole-3,4'-piperidine) hydrochloride). SB 236057-A
      has been shown to have high affinity for human 5-HT1B receptors (pK(i) = 8.2) and
      displays 80 or more fold selectivity for the human 5-HT1B receptor over other 5
      HT receptors and a range of additional receptors, ion channels and enzymes. In
      functional studies at human 5-HT1B receptors SB-236057-A displayed inverse
      agonism (pA(2) = 8.9) using [(35)S]GTPgammaS binding, and silent antagonism
      (pA(2) = 9.2) using cAMP accumulation. SB-236057-A also acted as an antagonist at
      the 5-HT terminal autoreceptor as measured by [3H]5-HT release from electrically
      stimulated guinea pig and human cortical slices. In the guinea pig,
      pharmacokinetic analysis demonstrated that SB-236057-A was bioavailable and
      according to in vivo pharmacodynamic assays it enters brain and has a long
      duration of action. Importantly no side effect liability was evident at relevant
      doses from anxiogenic, cardiovascular, sedative or migraine viewpoints. In vivo
      microdialysis studies demonstrated that SB-236057-A is an antagonist in the
      guinea pig cortex but has no effect on extracellular 5-HT levels per se. In
      contrast, SB-236057-A increased extracellular 5-HT levels in the guinea pig
      dentate gyrus. This increase in 5-HT release was comparable to that observed
      after 14 days of paroxetine administration. SB-236057-A has been a useful tool in
      confirming that, in either guinea pigs or humans, the terminal 5-HT autoreceptor
      is of the 5-HT1B subtype. It appears that acute 5-HT1B receptor blockade, by
      virtue of increased 5-HT release in the dentate gyrus, may provide a rapidly
      acting antidepressant.

PMID- 11830761
TI  - Phenibut (beta-phenyl-GABA): a tranquilizer and nootropic drug.
AB  - Phenibut (beta-phenyl-gamma-aminobutyric acid HCl) is a neuropsychotropic drug
      that was discovered and introduced into clinical practice in Russia in the 1960s.
      It has anxiolytic and nootropic (cognition enhancing) effects. It acts as a GABA
      mimetic, primarily at GABA(B) and, to some extent, at GABA(A) receptors. It also
      stimulates dopamine receptors and antagonizes beta-phenethylamine (PEA), a
      putative endogenous anxiogenic. The psychopharmacological activity of phenibut is
      similar to that of baclofen, a p-Cl-derivative of phenibut. This article reviews
      the structure-activity relationship of phenibut and its derivatives. Emphasis is
      placed on the importance of the position of the phenyl ring, the role of the
      carboxyl group, and the activity of optical isomers. Comparison of phenibut with
      piracetam and diazepam reveals similarities and differences in their
      pharmacological and clinical effects. Phenibut is widely used in Russia to
      relieve tension, anxiety, and fear, to improve sleep in psychosomatic or neurotic
      patients; as well as a pre- or post-operative medication. It is also used in the
      therapy of disorders characterized by asthenia and depression, as well as in post
      traumatic stress, stuttering and vestibular disorders.

PMID- 11830762
TI  - Indirect effects in aquatic ecotoxicology: implications for ecological risk
      assessment.
AB  - Understanding toxicant effects at higher levels of biological organization
      continues to be a challenge in ecotoxicology and ecological risk assessment. This
      is due in part to a tradition in ecotoxicology of considering the direct effects
      of toxicants on a limited number of model test species. However, the indirect
      effects of toxicity may be a significant factor influencing the manner in which
      ecosystem structure and function respond to anthropogenic stressors.
      Subsequently, failure to incorporate indirect effects into risk assessment
      paradigms may be a significant source of uncertainty in risk estimates. The
      current paper addresses the importance of indirect effects in an ecotoxicological
      context. Laboratory, mesocosm, and whole ecosystem research into indirect effects
      is reviewed. The implications of indirect effects for ecological risk assessment
      and potential areas of profitable future research are also discussed.

PMID- 11830763
TI  - Visual aesthetic quality of Northern Ontario's forested shorelines.
AB  - Only a few empirical studies on forest aesthetics have adopted a water-based
      perspective for observers and have investigated the perceived visual quality of
      forested shorelines. In forested environments with many lakes, such as the boreal
      forest in the Canadian Shield, individuals have greater exposure to forests from
      water-based rather than in-stand vantage points. This study employed the
      psychophysical research direction to explore the relationships between scenic
      beauty and biophysical characteristics of the forested shorelines in the boreal
      forests. Two model forms were tested. One model related the variation of
      shoreline forest aesthetic evaluations of near-vista views (140 m offshore) to a
      set of forest mensuration data. Tree size, tree mortality, conifer shrubs, tree
      density, amount of hardwood, and slope explained 60.2% of the variance in scenic
      beauty between the study sites. A second model was calibrated to test the
      relationship between an already existing ecosystem vegetation classification
      system and the aesthetic evaluations of the same forested shorelines. When the
      ecosystem classification was simplified to eight groups, the model explained
      48.5% of variance. These models suggest that the psychophysical approach to
      studying aesthetics can be applied successfully to near-vista evaluations of
      scenic beauty. The finding that a forest ecosystem classification system is
      highly related to scenic beauty suggests that, at least in the boreal forest,
      managers can reasonably estimate the scenic beauty of forested shoreline
      environments from an ecosystem classification, with little need for intensive
      data on these sites.

PMID- 11830764
TI  - Environmental vulnerability indicators for environmental planning and decision
      making: guidelines and applications.
AB  - Environmental decision-making and policy-making at all levels refers necessarily
      to synthetic, approximate quantification of environmental properties such as
      vulnerability, conservation status, and ability to recover after perturbation.
      Knowledge of such properties is essential to informed decision-making, but their
      definition is controversial and their precise characterization requires
      investments in research, modeling, and data collection that are only possible in
      the most developed countries. Environmental agencies and governments worldwide
      have increasingly requested numerical quantification or semiquantitative ranking
      of such attributes at the ecosystem, landscape, and country level. We do not have
      a theory to guide their calculation, in general or specific contexts,
      particularly with the amount of resources usually available in such cases. As a
      result, these measures are often calculated with little scientific justification
      and high subjectivity, and such doubtful approximations are used for critical
      decision-making. This problem applies particularly to countries with weak
      economies, such as small island states, where the most precious environmental
      resources are often concentrated. This paper discusses frameworks for a "least
      disappointing," approximate quantification of environmental vulnerability. After
      a review of recent research and recent attempts to quantify environmental
      vulnerability, we discuss models and theoretical frameworks for obtaining an
      approximate, standardizable vulnerability indicator of minimal subjectivity and
      maximum generality. We also discuss issues of empirical testing and comparability
      between indicators developed for different environments. To assess the state of
      the art, we describe an independent ongoing project developed in the South
      Pacific area and aimed to the comparative evaluation of the vulnerability of
      arbitrary countries.

PMID- 11830765
TI  - Toward improved environmental and social management of Indian shrimp farming.
AB  - In the last decade, Indian shrimp aquaculture production tripled from 30,000 tons
      (1990) to 102,000 tons (1999). This fast development, combined with a lack of
      adequate planning and regulation, caused a number of environmental problems and
      social conflicts, including conversion of mangroves, water pollution, and
      salinization of drinking water wells. Because of the significant investments made
      in shrimp culture and the size of the environmental and social impacts, the
      formulation of a regulatory framework for shrimp aquaculture has been subject to
      an intensive debate between the aquaculture and the environmental lobbies.
      Following an order from the Supreme Court (1996), the Aquaculture Authority was
      established and a regulatory and institutional framework for the shrimp
      aquaculture sector has been set up. However, implementation of the system is
      still defective, and there is an urgent need for improvement. Farmers are
      increasingly able to prevent the devastating white spot disease in shrimps, and
      in the absence of proper planning and regulation, further expansion of shrimp
      production could result in significant additional environmental and social costs.
      The environmental and social management of Indian shrimp farming can be improved
      through a mix of policy measures, including strengthening of the license system,
      more effective enforcement of regulations, the use of economic incentives, and
      increased monitoring of environmental and social impacts.

PMID- 11830766
TI  - The relative importance of sources of greenhouse-gas emissions: comparison of
      global through subnational perspectives.
AB  - Increasing atmospheric concentrations of greenhouse gases are widely expected to
      cause global warming and other climatic changes. It is important to establish
      priorities for reducing greenhouse-gas emissions, so that resources can be
      allocated efficiently and effectively. This is a global problem, and it is
      possible, on a global scale, to identify those activities whose emissions have
      the greatest potential for enhancing the greenhouse effect. However, perspectives
      from smaller scales must be appreciated, because it is on scales down to the
      local level that response measures will be implemented. This paper analyzes the
      relative importance of emissions from the many individual sources, on scales
      ranging from global to national to subnational. Individual country perspectives
      and proposed policy measures and those of subnational political entities exhibit
      some commonalities but differ among themselves and from a global-scale
      perspective in detail.

PMID- 11830767
TI  - Remote assessment of forest health in southern Arizona, USA: evidence for ozone
      induced foliar injury.
AB  - This paper examines possible ozone-induced foliar injury to ponderosa pine areas
      in the Rincon Mountains of southern Arizona from 1972 to 1992. Spatiotemporal
      differences in a satellite-derived vegetation index (VI) are examined with
      respect to antecedent moisture conditions, temporal variations in ozone exposure
      levels, and measured foliar injury values from 1985. Seasonal ozone exposure
      levels (SUM60 and W126) increased from 1982 to 1998 and were significantly
      correlated (r = 0.49 and 0.53, alpha = 0.05) with annual population totals in the
      Tucson area. Extensive masking of satellite images from 1972, 1986, and 1992
      resulted in two optimal change detection areas, with one site, TVWMica, exposed
      mostly to the Tucson air pollution plume, while the other site, EMica, was more
      protected from Tucson-derived pollution. An overall increase in VI from 1972 to
      1992 at both sites appears to have been caused by an increase in moisture
      availability. Larger foliar injury values in 1985 were associated with a smaller
      increase in VI (i.e., a smaller increase in green leaf biomass) from 1972 to
      1986. From 1972 to 1986 and from 1986 to 1992, VI values at TV/WMica increased at
      a slower rate compared to those at EMica. The reduced increase in "green-up" may
      have been caused partially by ozone-induced foliar injury and resulting decreases
      in green leaf biomass. However, these spatial differences in VI values may have
      also been caused by a number of other factors. Results nevertheless reveal the
      strong possibility of distinct, topographically based, spatial variations in
      ozone-induced foliar injury within the Rincons.

PMID- 11830768
TI  - Potential for using native plant species in stormwater wetlands.
AB  - Spartina pectinata (prairie cordgrass) was grown under five hydroperiods (wet-dry
      cycles) to determine its potential for use in stormwater wetlands, particularly
      as an alternative to the highly invasive Phalaris arundinacea (an exotic grass).
      Rhizomes planted in outdoor microcosms grew vigorously in all treatments, namely,
      weekly flooding in early summer, weekly flooding in late summer, flooding every
      three weeks throughout the summer, weekly flooding throughout the summer, and no
      flooding. Neither the timing nor frequency of 24-hour floods (10-20 cm deep)
      affected total stem length (grand mean 1003 +/- 188.8 cm per pot, n = 140) or
      above-ground biomass (46.5 +/- 8.3 g per pot, equivalent to approximately 360
      g/m2). However, by late summer, fewer new tillers were found in unflooded
      microcosms, indicating that vegetative expansion is drought-sensitive. The growth
      of Spartina plants was further assessed with and without Glyceria striata (a
      native grass) and Phalaris arundinacea. Glyceria growth was not affected by
      hydrologic treatment. Glyceria reduced Spartina growth by approximately 11%,
      suggesting potential as a cover crop that might reduce establishment and growth
      of Phalaris seedlings. Seeds of Phalaris did not germinate, but branch fragments
      established where soil was moist from flooding, regardless of the presence of
      Glyceria. The ability of Spartina to establish vegetatively and grow well under
      variable water levels leads us to recommend further testing in stormwater
      wetlands, along with early planting of Glyceria to reduce weed invasions.

PMID- 11830769
TI  - Fire management of California shrubland landscapes.
AB  - Fire management of California shrublands has been heavily influenced by policies
      designed for coniferous forests, however, fire suppression has not effectively
      excluded fire from chaparral and coastal sage scrub landscapes and catastrophic
      wildfires are not the result of unnatural fuel accumulation. There is no evidence
      that prescribed burning in these shrublands provides any resource benefit and in
      some areas may negatively impact shrublands by increasing fire frequency.
      Therefore, fire hazard reduction is the primary justification for prescription
      burning, but it is doubtful that rotational burning to create landscape age
      mosaics is a cost effective method of controlling catastrophic wildfires. There
      are problems with prescription burning in this crown-fire ecosystem that are not
      shared by forests with a natural surface-fire regime. Prescription weather
      conditions preclude burning at rotation intervals sufficient to effect the
      control of fires ignited under severe weather conditions. Fire management should
      focus on strategic placement of prescription burns to both insure the most
      efficient fire hazard reduction and to minimize the amount of landscape exposed
      to unnaturally high fire frequency. A major contributor to increased fire
      suppression costs and increased loss of property and lives is the continued urban
      sprawl into wildlands naturally subjected to high intensity crown fires.
      Differences in shrubland fire history suggest there may be a need for different
      fire management tactics between central coastal and southern California. Much
      less is known about shrubland fire history in the Sierra Nevada foothills and
      interior North Coast Ranges, and thus it would be prudent to not transfer these
      ideas too broadly across the range of chaparral until we have a clearer
      understanding of the extent of regional variation in shrubland fire regimes.

PMID- 11830770
TI  - Evaluating sediment stability at sites with historic contamination.
AB  - The stability of cohesive sediment deposits during a rare storm is a critical
      component in the evaluation of remedial options at a contaminated sediment site.
      Estimating scour depths during a rare storm, and the resulting contaminant
      concentrations in the surficial layer of the bed, is necessary for comparing the
      efficacy of various remedial alternatives. Evaluation of sediment stability is
      accomplished using sediment transport analyses that employ quantitative
      procedures. Qualitative analyses or conceptual models can be useful for
      developing and validating quantitative analysis tools; however, qualitative
      techniques alone generally are insufficient for conducting defensible remedial
      alternative evaluations. The level of analysis used for a specific site depends
      on data availability, required level of accuracy, and time and budget
      constraints. A tier 1 analysis involves the use of approximate equations to
      produce order-of-magnitude estimates of scour depths during a rare storm. The
      second tier of this analysis scheme employs the development and application of a
      sediment transport model to evaluate bed stability. State-of-the-science sediment
      transport models have been effectively used as management tools for evaluating
      remedial options at several contaminated sediment sites. It should not be
      presumed that rare storm events cause catastrophic impacts at the site under
      review. Two case studies demonstrate that a rare storm is not necessarily
      catastrophic; significant increases in surficial bed concentrations caused by
      reexposure of elevated concentrations buried at depth in the bed will not
      necessarily occur during a rare storm. However, it is important to note that
      sediment stability is site-specific.

PMID- 11830771
TI  - Detecting changes in natural resources using Land Condition Trend Analysis data.
AB  - The Land Condition Trend Analysis (LCTA) program is the US Army's standard for
      land inventory and monitoring, employing standardized methods of natural
      resources data collection, analyses, and reporting designed to meet multiple
      goals and objectives. Critical to using LCTA data in natural resources management
      decisions is the ability of the LCTA protocols to detect changes in natural
      resources. To quantify the ability of LCTA protocols to detect resource changes,
      power analysis techniques were used to estimate minimum detectable effect sizes
      (MDES) for selected primary and secondary management variables for three Army
      installations. MDES for a subset of primary variables were estimated using data
      from 27 installation LCTA programs. MDES for primary and secondary variables
      varied widely. However, LCTA programs implemented at larger installations with
      lower sampling intensities detected changes in installation resources as well as
      programs implemented at smaller more intensively sampled installations. As a
      national monitoring program that is implemented at individual installations, LCTA
      protocols provide relatively consistent monitoring data to detect changes in
      resources despite diverse resource characteristics and implementation
      constraints.

PMID- 11830772
TI  - Evaluation of the first phase of sulfur dioxide and nitrogen oxides provisions of
      the 1990 Clean Air Act: a plant-based approach.
AB  - Electric power generating plants that use coal were among the key targets of
      Title IV of the 1990 Clean Air Act. Under the first phase of the act, 110 coal
      fired electric power plants were required to reduce their sulfur dioxide
      emissions by 1995 and nitrogen oxide emissions by 1996. Phase 2 of the act
      requires even greater reduction of sulfur dioxide emissions by 2000 and nitrogen
      oxide emissions by 2008. This study examines whether the 107 targeted plants
      (three plants went off-line) have achieved the desired sulfur dioxide and
      nitrogen oxide emission levels. The analysis of sulfur dioxide is based on data
      from 1990, 1995, and 1999. The findings show that although sulfur oxide increased
      by 3% from 1995 to 1999, it decreased by 45% over the 1990-1999 period at the
      firm level for the targeted firms. The findings also indicate that the overall
      reduction in sulfur dioxide was achieved by utilizing low sulfur coal and by
      purchasing emission allowances. So far as nitrogen oxides are concerned, there
      has been a reduction of 14% over the 1990-1999 period, of which 7% was achieved
      during the 1995-1999 period. An evaluation of emissions at the plant level
      indicates that several plants do not meet the emissions level for sulfur dioxide
      or nitrogen oxides. These results provide a mixed scorecard for reduction in
      emissions both for sulfur dioxide and nitrogen oxides. Even though there is
      reduction in the emissions on an overall basis at the firm level, several plants
      that have not been able to reduce emissions deserve special attention to meet the
      goals of the act in reducing emissions.

PMID- 11830773
TI  - Thecaloscopy part II: anatomical landmarks.
AB  - Endoscopic anatomy differs from microsurgical anatomy. Topographical orientation
      as well as the proportion of objects, is different as they depend on the
      lens/object distance. Orientation under endoscopic conditions requires structures
      with defined positions or recognisable structures previously identified
      radiolologically. Structures are anatomical landmarks if the topographical
      relation to their surroundings is constant and they are easy and reliable to
      recognise. The contents of the dural sack are nerve roots with their supplying
      vessels, arachnoid trabeculars, filum terminale, and CSF. Safe navigation of a
      thecaloscope in relation to the bony structures is only possible with the
      simultaneous use of intraoperative fluoroscopy. To facilitate the navigation of
      scopes and instruments in the subarachnoid space we attempted to identify and
      describe reliable, and therefore constant recognisable anatomical landmarks.

PMID- 11830774
TI  - Application of flexible neuroendoscopes to intracerebroventricular arachnoid
      cysts in children: use of videoscopes.
AB  - Videoscopes used in other parts of the human body are potential tools for
      neuroendoscopy as long as they are slim enough, because they provide
      exceptionally high resolution images. We describe the application of flexible
      videoscopes and neuroendoscopes developed in Japan to intraventricular arachnoid
      cysts in children. Thirty-eight children with middle fossa arachnoid cysts were
      treated either by conventional cystoperitoneal shunting operations (n = 28) or by
      neuroendoscopes (n = 10). Neuroendoscopic operations such as cyst fenestration
      were highly useful, eliminating the need for open surgery for cyst
      excision/fenestration or cystoperitoneal shunting operations in all of the
      patients during a mean follow-up period of 17.7 months. Statistically highly
      significant reductions were observed in the major complications (p < 0.0001 by
      chi(2)-test) because shunting operations were inevitably accompanied by shunt
      malfunction, infection, or dependence. Compared to the traditional
      neuroendoscopes, our slim videoscopes provided outstanding image quality,
      allowing for more comprehensive examination and treatment while minimizing
      operative trauma.

PMID- 11830775
TI  - Endoscopic endonasal approach to the optic nerve: a technical note.
AB  - An endoscopic endonasal technique was used in the surgical treatment of a
      meningioma compressing the optic nerve. The patient was a 58-year-old woman who
      had experienced progressive visual loss in her left eye. Magnetic resonance (MR)
      scans of the brain demonstrated a contrast-enhancing tumor mass, which was
      measured to be 10 x 15 mm in size, compressing the left optic nerve. Automated
      visual field examination confirmed left-eye visual field defects, the temporal
      visual field worse than the nasal. The tumor was excised in total endoscopically
      through her right nostril. Histological diagnosis was meningothelial meningioma.
      Her hospital stay was overnight. Her left-eye vision improved with a residual
      crescentic temporal-field defect. She has done well without tumor recurrence as
      evidenced by a 20-month follow-up. This is the first report describing endoscopic
      endonasal removal of an intracranial tumor compressing the optic nerve.

PMID- 11830776
TI  - Endoscopic approach to intraventricular cysticercal lesions.
AB  - Various surgical approaches to treat intraventricular cysticercosis have been
      practiced over the years. We now present our experience with the use of the
      endoscope in the removal of intraventricular cysticercal cysts in patients with
      intraventricular cysticercal lesions associated with hydrocephalus. From 1995 to
      1998, we have excised intraventricular cysticercal cysts from 9 patients. They
      were located in lateral ventricle in 4, in the third ventricle in two and in the
      fourth ventricle in three patients. A Gaab's rigid neuroendoscope system was used
      to enter and excise cysts in the lateral and third ventricle. The flexible
      fiberoptic scope was used for excising cysts in the fourth ventricle, through a
      transaqueductal route. In all cases a precoronal frontal burr hole was used for
      entry. All have been treated with albendazole in the postoperative period. All
      the cysts were removed successfully using endoscopic neurosurgery alone. One
      patient had a superficial injury to the rigid side of the aqueduct with a
      postoperative deficit, which improved. Three septal perforations, three third
      ventriculostomies, and one aqueductoplasty were done in the same sitting after
      cyst removal for CSF diversion. None of the nine cases required further surgery
      up to date. The follow-up period varied from 12 to 45 months with a median of 18
      months. Endoscopic neurosurgery is a minimally invasive technique enabling
      removal of intraventricular cyticercal cysts from all locations, avoiding major
      craniotomies/posterior fossa explorations and shunts.

PMID- 11830777
TI  - Recurrent cubital tunnel syndrome. Etiology and treatment.
AB  - Controversy surrounds the treatment of recurrent cubital tunnel syndrome after
      previous surgery. Irrespective of the surgical technique, namely pure
      decompression in the ulnar groove and the cubital tunnel distal of the medial
      epicondyle, and the different methods of volar transposition (subcutaneous,
      intramuscular, and submuscular), the results of surgical therapy of cubital
      tunnel syndrome are often not favorable, especially in cases of long-standing
      symptoms and severe deficits. Twenty-two patients who had previously undergone
      surgical treatment for ulnar nerve entrapment at the elbow were evaluated because
      of persistent or recurrent pain, paresthesia, numbness, and motor weakness. Ten
      patients had undergone a nerve transposition, 5 patients underwent a simple
      decompression of the ulnar nerve, and 7 patients experienced two previous
      operations with different surgical techniques. Two patients underwent surgery at
      our hospital, whereas 20 patients underwent their primary surgery at other
      institutions. Various surgical techniques were used during the subsequent
      surgery, such as external neurolysis, subcutaneous anterior transposition, and
      subsequent transfer of the nerve back into the sulcus. The causes of continued or
      recurrent symptoms after initial surgery included dense perineural fibrosis of
      the nerve after subcutaneous transposition, adhesions of the nerve to the medial
      epicondyle and retention of the medial intermuscular septum. The average follow
      up after the last procedure was 7 months (2 - 20 months). All 7 patients with
      subsequent transfer of the ulnar nerve back into the sulcus became pain-free,
      whereas only 11 of 15 patients who had external neurolysis or subcutaneous
      transposition became free of pain or experienced reduced pain. The recovery of
      motor function and return of sensibility were variable and unpredictable. In
      summary, reoperation after primary surgery of cubital tunnel syndrome gave
      satisfactory results in 18 of 22 cases. Subsequent transfer of the ulnar nerve
      back into the sulcus promises to be useful in cases in which subcutaneous
      transposition had not been successful.

PMID- 11830778
TI  - Measurement of median nerve blood flow during carpal tunnel release with laser
      Doppler flowmetry.
AB  - Eight consecutive median nerves in eight patients with clinical carpal tunnel
      syndrome were prospectively examined by non-contact laser Doppler flowmetry
      before and after undergoing carpal tunnel release. Before performing carpal
      tunnel release, the difference in the median nerve blood flow between the values
      at the distal and proximal portions to the transverse carpal ligament was
      statistically significant (p = 0.021). After carpal tunnel release, the median
      nerve blood flow both distal and proximal to the transverse carpal ligament
      increased by 1.5 and 1.3 times, respectively, compared to the flow prior to
      carpal tunnel release, however, only the difference at the distal portion to the
      transverse carpal ligament was statistically significant (p = 0.015). In this
      study, we directly measured the median nerve blood flow using non-contact laser
      Doppler flowmetry and thus demonstrated a significant difference in the median
      nerve blood flow between the values at the distal and proximal portions to the
      transverse carpal ligament before carpal tunnel release and a significant
      increase in the nerve blood flow only at the distal portion to the transverse
      carpal ligament after surgery. This technique is thus considered to be an easy
      and reproducible way to intraoperatively evaluate the nerve blood flow in real
      time during the release of entrapment neuropathies.

PMID- 11830779
TI  - Treatment of dural arteriovenous fistulae (dAVF's) at the superior sagittal sinus
      (SSS) using embolisation combined with micro- or radiosurgery.
AB  - DAVF's at the SSS are extremely rare and usually present with intracranial
      haemorrhage (ICH) or a progressive neurological deficit. Due to their midline
      location and multiple arterial supply, endovascular treatment alone often fails
      in eliminating the fistula. Therefore, endovascular, combined with neurosurgical
      and/or radiosurgical treatment is often needed to cure the patient. We summarized
      our experience with three male patients over a ten-year period who suffered from
      dAVF's involving the middle and posterior third of the SSS. Two of them presented
      with an ICH during the clinical course. Despite multiple transarterial
      embolisations, complete fistula occlusion could not be achieved in any of them.
      Nevertheless, neurological symptoms improved in all cases. One patient refused
      further treatment and died six years later due to an ICH. Another patient was
      finally cured by microsurgical coagulation of the fistula. In the remaining
      patient stereotactic radiosurgery (SRS) was performed after nearly complete
      endovascular occlusion. We strongly recommend microsurgery and/or radiosurgery as
      adjunctive measures, if embolisation alone fails to eliminate these dangerous
      fistulae.

PMID- 11830780
TI  - Gamma knife radiosurgery in meningiomas of the posterior fossa. Experience with
      62 treated lesions.
AB  - OBJECTIVES: This study was undertaken to assess the role of the gamma knife (GK)
      in the treatment of meningiomas of the posterior cranial fossa (PCF) and to
      statistically analyze the predictability of arbitrarily-selected prognostic
      factors in such treatment. METHODS: From February 1993 to November 1998, 57
      patients underwent GK treatment for 62 meningiomas of the PCF (19 M/38 F; average
      age, 57.5 years, ranging from 25 - 82 years). Tumor sites included: foramen
      jugular-petrous bone (26/62), petroclival (23/62), cerebellar convexity (6/62),
      tentorium (6/62), and foramen magnum (1/62). Single lesions were treated in 44/62
      cases while meningiomatosis was treated in the remaining 18. Post-operative
      residual or recurrent tumor was found in 27/62 patients and, in 7/27, histology
      documented characteristics of biological aggressiveness (GII/III). Indications
      for radiosurgery included: advanced age, high operative risk, tumor volume < 20
      ml, inoperable or refused for additional surgery. The prognostic factors
      statistically analyzed included: meningiomatosis (yes/no), radiosurgery as
      primary or adjuvant treatment, GI vs. GII/III histology, and tumor volume (< or =
      5 ml vs. > 5 ml). RESULTS: The observation periods varied from 6 to 64.3 months
      (median 28.7 months). At the end of the study, 53/57 patients were alive and
      reported to be in stable or improved neurological condition. The cause of death
      for the remaining 4 patients included: 2 deaths associated with tumor
      progression, while 2 died due to causes unrelated to the disease.
      Neuroradiological evaluation documented the disappearance or reduction of the
      meningioma mass in 34/62 (55 %) cases, a stable imaging picture in 25/62 (40 %),
      and a progression only in 3/62 (5 %). To date, there have been no reported cases
      of post-GK permanent morbidity or mortality. Side effects observed were of a
      transient nature due to post-radiosurgical edema (6.5 %). With regard to
      statistical analysis, the only factor to appear to significantly influence
      efficacy of radiosurgery for tumor growth control (TGC) was the biological nature
      of the meningioma (chi(2) = 2.708). The presence of meningiomatosis, SR as a
      primary or adjuvant treatment nor tumor volume were shown to statistically
      influence tumor behavior after GK. CONCLUSIONS: The excellent results obtained
      for TGC with minimal associated side effects suggest that GK is an effective
      therapeutic tool also for treatment of PCF meningiomas.

PMID- 11830781
TI  - Successful low-dose intracavitary irradiation of a Rathke's cleft cyst with
      colloidal rhenium-186.
AB  - Symptomatic recurrence of an histologically verified intra- and suprasellar
      Rathke's cleft cyst (RCC) was observed 4 months following transsphenoidal
      microsurgery. The space-occupying cyst was treated by endocavitary irradiation
      with colloidal rhenium-186 via a previously implanted catheter with an attached
      subcutaneous reservoir. The calculated dose of 4.4 Gy was able to stop the
      production of cyst fluid. Follow-up after intracavitary irradiation extends over
      13 months. The cyst, with an initial size of 3 x 3 x 4 cm, has been reduced to
      1.1 x 1.06 x 1.2 cm. The production of cyst fluid has decreased from 25 - 30 ml
      within 2 months before treatment to zero. The patient's visual and mental status
      as well as her quality of life are normal.

PMID- 11830782
TI  - Minimally invasive approach to traumatic intracerebral hematomas.
AB  - Trauma is one of the leading causes of death in Brazil. We report on 28 cases of
      traumatic intracerebral hematomas operated on via a minimally invasive approach.
      A simplified method of localization and right placement of the burr hole is
      described in details, as well as the technique used in all cases. Every patient
      was submitted to pre- and postoperative CT scan (computerized tomography) and had
      the volume of the hematoma measured before the surgical procedure to compare the
      efficacy of the treatment. No patient needed a second operation, even though in
      some cases there were residual hematomas. We believe that this approach can be
      done with safety and replace a standard craniotomy in selected cases.

PMID- 11830783
TI  - Stereotactic biopsy of brain stem lesions.
AB  - The successful therapy of space-occupying lesions of the brain stem, depends on
      precise histological diagnosis. Although the clinical management and contemporary
      imaging techniques (computerized tomography and magnetic resonance imaging) are
      now able to reveal and approach the diagnosis in these cases, only the
      combination of these two with the use of contemporary stereotactic systems, is
      able to secure the precise histological diagnosis for the patient with a good
      degree of safety. This study presents the first five patients in Greece with
      space-occupying lesions of the brain stem, in whom a stereotactic biopsy was
      carried out. All patients were subjected to CT-guided stereotactic biopsy, via
      the frontal approach in 4 patients with lesions in the superior pons and the
      mesencephalon and in one patient via the transcerebellar approach, for a lesion
      in the lateral surface of the pons. Precise histological diagnosis was possible
      and on the basis of a reliable choice of histological criteria the appropriate
      therapeutic approach was chosen, thus avoiding the old "empirical" treatment.

PMID- 11830784
TI  - Surgery of lesions in the motor strip combining a stereotactically-guided mini
      craniotomy with electrophysiological mapping of the motor cortex.
AB  - The removal of space-occupying lesions in the sensori-motor cortex carries a
      considerable risk of postoperative palsy. Therefore subcortical lesions located
      in the sensori-motor strip are often considered to be inoperable. Treatment
      options are stereotactic biopsy and radiosurgery beside radiological control
      examinations without surgery or surgery with a higher risk of postoperative
      deficits. The following article focusses on a combined approach involving a
      stereotactically guided and electrophysiologically controlled surgery. The
      instruments used (stereotactical system and electric stimulator) are available in
      almost every neurosurgical department in the Western and Eastern world and had
      been the first navigation systems in the human brain.

PMID- 11830785
TI  - Navigated transcranial magnetic stimulation for presurgical planning--correlation
      with functional MRI.
AB  - PURPOSE: This paper describes the potential of navigated transcranial magnetic
      stimulation to map the motor cortex in patients with mass lesions near the
      primary motor cortex by comparing the results of this technique to those of
      functional MRI. MATERIAL AND METHODS: Ten patients with mass lesions near the
      central sulcus were studied preoperatively using a figure-of-eight transcranial
      magnetic stimulator attached to a neuronavigation system to allow for direct
      visualization of the stimulated brain region. Subsequently, in all patients a
      blood oxygenation level dependent 2D multislice multishot T2*-weighted gradient
      echo EPI sequence on a 1.5 T Philips Gyroscan during motor activation was
      performed. Results of both methods were coregistered and compared. RESULTS: The
      distances between the peak parenchymal fMRI activation and the cortical area
      where TMS elicited the maximum MEPs ranged between 0 and 1.2 cm (mean 0.6 cm, SD
      0.4 cm). CONCLUSION: We conclude that navigated TMS is a reliable alternative for
      localizing the motor-related areas in the human brain preoperatively and
      therefore may be a useful adjunct or, in selected patients, even a helpful
      alternative to functional MRI.

PMID- 11830786
TI  - Development and clinical application of near-infrared surgical microscope:
      preliminary report.
AB  - Visualization of near-infrared fluorescence through a surgical microscope can
      provide intraoperative information about deep-seated tissues. We studied the
      possibility of taking a near-infrared image through a surgical microscope after
      intravenous injection of indocyanine green (ICG). The surgical microscopes we
      used were Zeiss models OPMI MD and OPMI CS-NC. We used a halogen lamp as a light
      source, a band pass filter of 760 - 810 nm as an excitation filter, a laser light
      of 800 nm as an external light source, and a band pass filter of 820 - 920 nm as
      a barrier filter. Near-infrared fluorescence of vessels on the brain surface and
      of the dural sinus was visualized through the dura mater after intravenous
      injection of 25 mg ICG using a Hitachi KP-160 camera. Near-infrared fluorescence
      of vessels on the brain surface was observed through the dura mater. Venous
      images were clearer than were arterial ones. The dural sinus and the bridging
      veins were also clearly visualized. These results suggest that a clinical
      application of near-infrared fluorescence microscopy is possible. However, a
      stronger fluorescence emitted from ICG will be necessary for such a microscope to
      have practical use.

PMID- 11830788
TI  - [Impact of the DRG system for subacute and rehabilitative treatment in Sydney,
      New South Wales, Australia].
AB  - The forthcoming introduction of a DRG system in Germany has entailed numerous
      uncertainties for the agencies involved, for medical and care staff as well as
      all others having to do with the health care system, the patients included. As
      had previously been the case in other countries, this innovation is going to
      effect major changes in Germany as well. Notwithstanding, efforts to enhance
      specific, efficient and quality-assured medical care can, and are intended to, be
      undertaken in the future as well. This short report summarizes the impact
      introduction of a DRG system has had at the interface between acute care and
      subsequent rehabilitation in Sydney, New South Wales; concluding, future
      developments are outlined.

PMID- 11830787
TI  - [A DRG based future hospital funding scheme: state of implementation and impact
      in the field of rehabilitation].
AB  - With the statutory health insurance reform act 2000 the German government started
      to introduce a new hospital funding system based on an internationally used
      diagnosis related groups (DRGs) system. In June 2000 the German self
      administration board (consisting of the German hospital federation, the German
      statutory health insurance funds and the association of private health insurers),
      which is in charge of realizing this project, decided to develop the future
      German (Refined) DRG System (G-DRG) with reference to the Australian Refined DRG
      System (AR-DRG) Version 4.1. Replacement of the previous German hospital
      reimbursement system by the new DRG-based hospital funding system is planned for
      January 2003 on a voluntary basis. From January 2004 on, the change of the
      reimbursement system is to become mandatory for all hospitals with the exception
      of psychiatry. The new reimbursement system is intended to not only cover acute
      hospital care but also parts of early rehabilitation, palliative and sub-acute
      care. Because of its economic incentives the effects of DRG introduction in
      Germany will not only be limited to the hospital scene but will also affect
      rehabilitation.

PMID- 11830789
TI  - [Health economics analysis of prospective payment systems in medical
      rehabilitation].
AB  - The forthcoming introduction of the DRG-system as a new hospital funding system
      in Germany reinforced the discussion about a reform of the already existing
      funding system in medical rehabilitation. Experience and concepts from acute
      medicine, however, cannot be transferred directly to rehabilitation. The
      development of a patient classification system is a presupposition for
      prospective payment systems. Initial attempts in rehabilitation-specific patient
      classification systems already exist, even though a comprehensive approach is not
      yet noticeable. International patient classification systems scarcely seem to be
      transferable due to the specific German case-mix. The specific differences
      between acute medicine and medical rehabilitation relevant for the valuation of
      funding systems are analyzed. Particularly a reduction of the length of stay as a
      primary aim for the introduction of the DRG-system does not seem appropriate for
      medical rehabilitation. The existing funding system in medical rehabilitation is
      analyzed from an economic point of view. The cost management of the German
      pension insurance, being one of the rehabilitation providers in Germany, has
      achieved high quality standard of treatment as well as cost restriction. This
      funding system has been further developed during the last couple of years. Future
      developments are shown.

PMID- 11830790
TI  - [Can the classification of patients for phase B, C and D of neurological
      rehabilitation be done by FIM(tm) scores?].
AB  - The classification of patients for phase B, C and D of neurological
      rehabilitation follows the suggestions of the Bundesarbeitsgemeinschaft fur
      Rehabilitation (BAR) based on defined clinical criteria and on neurological
      rehabilitation assessment. The focus of this study is to define the intervals of
      the complete FIM(tm)-index, intervals covered empirically as well as by
      evaluations of physicians, that permit utmost accuracy in assigning patients to
      phase B, C and D of neurological rehabilitation. Therefore, data records of 3686
      patients from 4 neurological rehabilitation centres were evaluated. The patients'
      functional autonomy was classified by FIM(tm) on admission, in intervals of 14
      days and at discharge, at the same time all patients in addition were assigned to
      phases B, C or D by the rehabilitation centre physicians. Statistical analysis of
      a total of 11,247 links of the phase classifications and FIM-indexes at 6
      measurement points showed that correct correlation to phase B, C and D could be
      obtained on average in 79 to 89 % of the cases, based on the assumption that 18 -
      36 points of the FIM-index assign to phase B, 37 - 90 points to phase C and 91 -
      126 points to phase D. Discrimination between phases B and C could be obtained
      accurately in an average of 84 %, discrimination between phases C and D in an
      average of 89 %. Conformance of the FIM-intervals with TAR-based groups of care
      efforts compared to the evaluation by physicians indicate that the FIM(tm)
      represents the need for care with greater validity. If assignment to phases B, C
      and D would have been done on the basis of the FIM-index instead of evaluation by
      a physician, 8,9 % fewer patients would on admission have been classified for
      phase C but, instead, 4,5 % more patients for phase B and 4,4 % for phase D. In
      case of using the FIM-intervals for classification, 12,1 % more phase B patients
      could have changed to phases C or D. Of the phase C cases, 17,7 % could have been
      transferred to phase D before discharge. The number of phase D patients would
      have remained unchanged comparing admission and discharge. FIM-orientated
      classification for the phases of neurological rehabilitation offers considerable
      advantages: operationalized criteria, possibility of statistical evaluation,
      objectiveness, reliability, validity, reproducibility of the decisions,
      sensitivity to change, prognostic sensitivity, and suitability as an instrument
      for internal and external quality assurance.

PMID- 11830791
TI  - [Interfaces in rehabilitation: three models].
AB  - Interfaces can cause disruptions in the care provision process. They can,
      however, also signify a differentiated and specialized division of labour of the
      care providing system. Three models for the description of interfaces are
      presented and compared: a linear model oriented towards the continuity of the
      provision of care for individuals, the Principal Agent (PA) Model from contract
      theory, and a complex systems model. In all three models coupling and information
      management are identified as essential interface functions. In regard to
      optimisation possibilities, the linear model leads to the case-management
      concept, the PA Model to integrated forms of provision and systems theory to
      context controlling.

PMID- 11830792
TI  - [Mental activity hand orthosis control using the EEG: a case study].
AB  - A report is given on the realization of a steering mechanism of a hand orthosis
      for a patient with paraplegia. An EEG-based Brain-Computer Interface (BCI) was
      used here for the first time, transferring purely mental activity to a control
      signal. This means that the patient has the capability to open or close the hand
      orthosis only by imagination of a movement. At this time, after a training period
      of about four months, the patient is able to move the hand orthosis with a
      certainty of almost hundred percent. The restored grasp function was verified by
      a grasp function test. Results are compared to those obtained using a
      conventional EMG-controlled orthosis.

PMID- 11830793
TI  - [Oncological rehabilitation: evaluation of the efficiency of inpatient
      rehabilitation].
AB  - BACKGROUND: There are only few studies on the evaluation of the efficiency of
      oncologic rehabilitation. The objective of this study was to determine the
      efficiency of a complex rehabilitation programme consisting of medical care,
      physical therapy, sports therapy, psychological support and health care seminars.
      Therefore the rehabilitation requirement at admission and the rehabilitation
      result at discharge were assessed in a patient sample. METHODS: To determine the
      rehabilitation requirement and the rehabilitation result, a self-assessment
      patient questionnaire was used (IRES, Indicators of Reha Status). This
      questionnaire allows establishing essential patient's parameters, which, besides
      the medical reports and the doctors' and therapists' opinions, are relevant for
      the Reha aims and important for the treatment strategy. The IRES instrument is a
      reliable, valid, sensitive and standardized multidimensional test instrument for
      assessment and outcome measurement in rehabilitation comprising parameters of
      somatic, functional and psychosocial issues. With the questionnaire the
      rehabilitation requirement was determined at the various measuring points as
      "Reha-status" with the three main dimensions "somatic status", "functional
      status" and "psychosocial status" or as distress scales (score values 0 - 10).
      The data were collected at admission to inpatient rehabilitation (T0) and at
      discharge (T1). RESULTS: At T0 967 patients with various oncologic diseases
      (breast cancer, gastrointestinal cancer, urogenital cancer, haematological and
      lymphatic systemic diseases, and various other types of cancer) were included
      into the study. At discharge (T1) 900 patients were included; subject to
      evaluation at T0 and T1 were n = 883 patients. Average age was 55,7 +/- 11,9
      years; 55,7 % were female, 44,3 % male. According to "Reha-status" 44 % were
      "extremely suspect" (IRES-score 5,4 +/- 0,8), 26 % "suspect" (6,8 +/- 0,4), and
      30 % "normal" (7,9 +/- 0,6) in comparison to a norm-reference test. Pre/post
      analysis (T0/T1) of the sample revealed a significant improvement of "Reha
      status" (T0 = 6,6 +/- 1,2/T1 = 6,81 +/- 1,3; p < 0,001). Significant improvements
      were also noticed for the subdimensions "somatic status" (T0 = 5,9 +/- 1,5/T1 =
      6,1 +/- 1,6; p < 0,001) and "psychosocial status" (T0 = 6,9 +/- 1,5/T1 = 7,2 +/-
      1,5; p < 0,001), whereas "functional status" had not changed significantly (T0 =
      7,1 +/- 1,6/T1 = 7,2 +/- 1,5; p > 0,05). Especially distinct improvements were
      observed in "psychosocial status" and in the distress scales, which are
      particular relevant in oncological patients. CONCLUSIONS: This investigation
      demonstrates that use of the IRES instrument is feasible also in clinical
      routine, hence supporting the determination of the patient's individual
      rehabilitation requirement and his or her individual rehabilitation aims. The
      findings confirm that during rehabilitation measurable and statistically
      significant positive effects are achieved in the somatic and psychosocial fields.
      In summary, this study shows that the complex programme of oncological inpatient
      rehabilitation achieves relevant changes within important distress issues of the
      patients.

PMID- 11830796
TI  - Severe demyelinating myelopathy with low human T cell lymphotropic virus type 1
      expression after transfusion in an immunosuppressed patient.
AB  - We describe an immunosuppressed patient who developed myelopathy after
      transfusion with human T cell lymphotropic virus type 1-infected blood products
      during cardiac transplantation; immunoglobulins and fibrinogen deposition
      indicated disruption of the blood-brain barrier. The low degree of inflammation
      and virus expression suggests that demyelination may have been caused by an
      antibody- and complement-mediated process and by an alteration of the spinal cord
      microenvironment with activation of microglial cells and astrocytes.

PMID- 11830797
TI  - Clinical and economic evaluation of rapid influenza a virus testing in nursing
      homes in calgary, Canada.
AB  - The incremental benefits and costs of a rapid influenza A virus infection
      diagnostic service were studied in nursing homes in Calgary, Canada, during a
      single influenza season. The service was used to test 159 patients with suspected
      infection in a group of "experimental" nursing homes and results were compared
      with those for a group of "control" homes. An equal number of cases of influenza
      were identified in each group. Twenty-eight patients (17.6%) had confirmed cases,
      and 63 patients (39.6%) had probable cases. A rapid viral test result was
      provided much faster for patients in the experimental homes (P=.005). Both groups
      had the same median attack rate for influenza A virus. In experimental homes, the
      duration of the outbreak was shorter (P=.03), and the cost of laboratory testing
      and the total cost (less the hospital cost) tended to be lower (P<.2). The rapid
      testing service also tended to lower the overall use of resources.

PMID- 11830798
TI  - Propionibacterium acnes chest infections in patients with chronic granulomatous
      disease: case reports.
AB  - Antibiotic prophylaxis in patients with chronic granulomatous disease (CGD) has
      decreased the prevalence of infections, but uncommon microorganisms are being
      observed more frequently. Propionibacterium acnes, a saprophyte of the skin, is
      generally not involved in infections other than acne. Two cases of P. acnes
      extracutaneous infections in teenagers with CGD are reported.

PMID- 11830799
TI  - Cerebral nocardiosis characterized by magnetic resonance spectroscopy in vivo.
AB  - We describe a patient with multiple cerebral lesions that initially were believed
      to be tumor metastases but were later found to be caused by Nocardia asteroides,
      after magnetic resonance spectroscopy (MRS) findings suggested that the lesions
      were infective in origin. This case report demonstrates the ability of MRS, a
      noninvasive imaging modality, to aid in the diagnosis of brain infection.

PMID- 11830800
TI  - Three consecutive outbreaks of Serratia marcescens in a neonatal intensive care
      unit.
AB  - We investigated an outbreak of Serratia marcescens in the neonatal intensive care
      unit (NICU) of the University Hospital of Zurich. S. marcescens infection was
      detected in 4 children transferred from the NICU to the University Children's
      Hospital (Zurich). All isolates showed identical banding patterns by pulsed-field
      gel electrophoresis (PFGE). In a prevalence survey, 11 of 20 neonates were found
      to be colonized. S. marcescens was isolated from bottles of liquid theophylline.
      Despite replacement of these bottles, S. marcescens colonization was detected in
      additional patients. Prospective collection of stool and gastric aspirate
      specimens revealed that colonization occurred in some babies within 24 hours
      after delivery. These isolates showed a different genotype. Cultures of milk from
      used milk bottles yielded S. marcescens. These isolates showed a third genotype.
      The method of reprocessing bottles was changed to thermal disinfection. In follow
      up prevalence studies, 0 of 29 neonates were found to be colonized by S.
      marcescens. In summary, 3 consecutive outbreaks caused by 3 genetically unrelated
      clones of S. marcescens could be documented. Contaminated milk could be
      identified as the source of at least the third outbreak.

PMID- 11830801
TI  - Persistence of immunity to live attenuated varicella vaccine in healthy adults.
AB  - The varicella vaccine was approved in 1995 for use in healthy varicella
      susceptible children and adults. Long-term immunity in 461 healthy adults who
      were enrolled in varicella vaccine trials in 1979-1999 were studied. Forty
      vaccinees (9%), including 19 (21%) of 89 vaccinees with household exposure (HHE)
      to chickenpox, developed breakthrough chickenpox 8 weeks to 11.8 years (mean, 3.3
      years) after vaccination. The median number of skin lesions among the 36
      untreated vaccinees was 20 (range, 1-240 lesions), and the number of lesions was
      essentially the same with time since vaccination. Breakthrough chickenpox was
      mild, even among vaccinees who did not have seroconversion or those recipients
      who lost detectable antibody. Lower varicella-zoster virus (VZV) antibody titers
      measured within 3 months of vaccination as well as at the time of HHE were
      associated with an increased risk of breakthrough disease. This study
      demonstrated that the varicella vaccine was effective in providing adults with
      long-term protection from serious VZV disease.

PMID- 11830802
TI  - Gatifloxacin-associated corrected QT interval prolongation, torsades de pointes,
      and ventricular fibrillation in patients with known risk factors.
AB  - Drugs not commonly considered to be cardioactive agents have been reported to
      cause prolongation of the corrected QT interval with resultant torsades de
      pointes or ventricular fibrillation. We report 4 cases of gatifloxacin-associated
      cardiac toxicity in patients with known risk factors for this adverse event.

PMID- 11830803
TI  - Infective endocarditis in elderly patients.
AB  - Infective endocarditis (IE) in elderly patients presents a unique diagnostic and
      therapeutic challenge. Atypical presentations frequently lead to delayed
      diagnosis and poor outcome. IE in elderly persons is somewhat more common among
      men. Underlying degenerative valvular disease, mitral valve prolapse, and the
      presence of a prosthetic valve are important risk factors predisposing elderly
      persons to IE. Streptococci and staphylococci are the predominant organisms,
      which are recovered from approximately 80% of elderly patients with IE. In older
      patients, IE occurs somewhat more frequently on the mitral valve than it does on
      the aortic valve. The presence of calcific valvular lesions and the prosthetic
      valves often confound the echocardiographic findings in elderly patients. A high
      index of suspicion and an aggressive diagnostic approach are required to ensure
      timely diagnosis and appropriate therapy.

PMID- 11830804
TI  - Tendon healing in a bone tunnel. Part I: Biomechanical results after
      biodegradable interference fit fixation in a model of anterior cruciate ligament
      reconstruction in sheep.
AB  - PURPOSE: Interference fit fixation of soft-tissue grafts has recently raised
      strong interest because it allows for anatomic graft fixation that may increase
      knee stability and graft isometry. Although clinical data show promising results,
      no data exist on how tendon healing progresses using this fixation. The purpose
      of the present study was to investigate anterior cruciate ligament (ACL)
      reconstruction biomechanically using direct tendon-to-bone interference fit
      fixation with biodegradable interference screws in a sheep model. TYPE OF STUDY:
      Animal study. METHODS: Thirty-five mature sheep underwent ACL reconstruction with
      an autologous Achilles tendon split graft. Grafts were directly fixed with poly
      (D,L-lactide) interference screws. Animals were euthanized after 6, 9, 12, 24,
      and 52 weeks and standard biomechanical evaluations were performed. RESULTS: All
      grafts at time zero failed by pullout from the bone tunnel, whereas grafts at 6
      and 9 weeks failed intraligamentously at the screw insertion site. At 24 and 52
      weeks, grafts failed by osteocartilaginous avulsion. At 24 weeks, interference
      screws were macroscopically degraded. At 6 and 9 weeks tensile stress was only
      6.8% and 9.6%, respectively, of the graft tissue at time zero. At 52 weeks,
      tensile stress of the reconstruction equaled 63.8% and 47.3% of the Achilles
      tendon graft at time zero and the native ACL, respectively. A complete
      restitution of anterior-posterior drawer displacement was found at 52 weeks
      compared with the time-zero reconstruction. CONCLUSIONS: It was found that over
      the whole healing period the graft fixation proved not to be the weak link of the
      reconstruction and that direct interference fit fixation withstands loads without
      motion restriction in the present animal model. The weak link during the early
      healing stage was the graft at its tunnel entrance site, leading to a critical
      decrease in mechanical properties. This finding indicates that interference fit
      fixation of a soft-tissue graft may additionally alter the mechanical properties
      of the graft in the early remodeling stage because of a possible tissue
      compromise at the screw insertion site. Although mechanical properties of the
      graft tissue had not returned to normal at 1 year compared with those at time
      zero, knee stability had returned to normal at that time. There was no graft
      pullout after 24 weeks, indicating that screw degradation does not compromise
      graft fixation.

PMID- 11830805
TI  - Tendon healing in a bone tunnel. Part II: Histologic analysis after biodegradable
      interference fit fixation in a model of anterior cruciate ligament reconstruction
      in sheep.
AB  - PURPOSE: Tendon-to-bone healing of soft-tissue grafts has been described to
      progress by the development of a fibrous interzone that undergoes a maturation
      process leading to the development of an indirect type of ligament insertion.
      Previous studies used extra-articular models or fixation far away from the joint
      line; thus, no data are available investigating tendon-to-bone healing of a soft
      tissue graft fixed anatomically. Therefore, we studied the tendon-to-bone healing
      of the anatomic soft-tissue graft interference fit fixation in a model of
      anterior cruciate ligament (ACL) reconstruction in sheep. TYPE OF STUDY: Animal
      study. METHODS: Thirty-five mature sheep underwent ACL reconstruction with an
      autologous Achilles tendon split graft. Grafts were directly fixed with
      biodegradable poly-(D,L-lactide) interference screws. Animals were euthanized
      after 6, 9, 12, 24, and 52 weeks and histologic evaluations were performed.
      Undecalcified specimens were evaluated under normal and polarized light.
      Additionally, animals received a polychrome sequential labeling (tetracycline,
      xylenol orange, and calcein green) to determine bone growth per time under
      fluorescent light. RESULTS: Intratunnel histologic findings at 6 weeks showed a
      tendon-bone junction with only a partial fibrous interzone between the graft
      tissue and the surrounding bone. A mature intratunnel tendon-bone junction with a
      zone of fibrocartilage was found at 9 to 12 weeks. At the tunnel entrance site a
      wide regular ligamentous insertion site was seen in all specimens after 24 weeks.
      This insertion showed regular patterns such as the direct type of insertion of a
      normal ligament with a dense basophilic transition zone consisting of mineralized
      cartilage. CONCLUSIONS: A fibrous interzone between the graft tissue and the bone
      tunnel was only partially developed, which is in contrast to all previous studies
      in which nonanatomic fixation was used. Thus, it is reasonable to assume that the
      tendon-to-bone healing in the present study may progress partially by direct
      contact healing without the development of a fibrous interzone. To our knowledge,
      this is the first report describing the development of a direct type of ligament
      insertion after ACL replacement with a soft-tissue graft. This is in contrast to
      previous studies reporting the development of an indirect type of insertion when
      using nonanatomic fixation far away from the joint line. Thus, histologic data
      strongly indicate that anatomic interference fit fixation is beneficial for
      tendon-to-bone incorporation by leading to the development of a direct type of
      ligament insertion.

PMID- 11830806
TI  - Arthroscopic repair of full-thickness tears of the rotator cuff: 2- to 14-year
      follow-up.
AB  - PURPOSE: This study was performed to evaluate 2 arthroscopic techniques for
      rotator cuff repair used by 1 surgeon for more than 12 years. The main objective
      of this study was to test the reliability of these arthroscopic repair techniques
      not only using clinical assessment during the follow-up, but through observation
      of the healing process of the tendons during the arthroscopic removal of the
      staples in our first group of patients. TYPE OF STUDY: This study was a
      before/after trial. METHODS: We present the results of arthroscopic repair of
      full-thickness rotator cuff tears in 100 patients. In group I, 35 patients had
      staple fixation, and in group II, 65 patients had side-to-side suture and anchor
      repair. Follow-up ranged from 2 to 14 years. All shoulders were evaluated using
      the UCLA rating scale. Shoulders repaired with staples (group I) were evaluated
      arthroscopically at staple removal. Arthroscopic subacromial decompression was
      performed in 26 of the 35 patients in group I and in 65 of the 65 patients in
      group II; 58 patients in group II had concomitant resection of distal clavicle.
      RESULTS: In group I, 22 patients (63%) had excellent results (UCLA scores, 34
      35), 7 (20%) had good results (UCLA scores, 28-33), 4 (11%) had fair results
      (UCLA scores, 21-27), and 2 (6%) of the patients had poor results (UCLA scores, 0
      20). In group II, 47 patients (72%) had excellent results (UCLA scores, 34-35),
      12 (19%) had good results (UCLA scores, 28-33), 2 (3%) had fair results (UCLA
      scores, 21-27), and 4 (6%) of the patients had poor results (UCLA scores, 0-20).
      CONCLUSIONS: Patients with well-healed rotator cuff tendons had satisfactory
      postoperative results and better overall functional results. The arthroscopic
      techniques for rotator cuff repair achieve results comparable to the results of
      traditional open repair. However, these technically demanding arthroscopic
      procedures require advanced arthroscopic skills and have a steep learning curve.

PMID- 11830807
TI  - Arthroscopic release of the rotator interval and coracohumeral ligament: An
      anatomic study in cadavers.
AB  - PURPOSE: The purpose of this cadaveric study was to examine the anatomy of the
      normal glenohumeral joint relevant to an arthroscopic rotator interval release
      and define both the endpoints of a complete release of the coracohumeral ligament
      and the relationship to surrounding tendons and nerves. TYPE OF STUDY: An
      anatomic cadaveric study. METHODS: Fifteen fresh-frozen cadaveric specimens were
      studied with 5 specimens in group I and 10 specimens in group II. Group I
      specimens were used to examine the relevant anatomy, including the structures at
      risk, the dimensions of the rotator interval, and potential endpoints for release
      of the coracohumeral ligament. Measurements included (1) the supraspinatus to the
      subscapularis distance, (2) the distance from the rotator interval to the deep
      surface of the coracoid process, and (3) the distance from the rotator interval
      to the coracoacromial ligament at the level of the glenoid. Group II specimens
      underwent arthroscopic release of the rotator interval using the appearance of
      the coracoacromial ligament as the superficial endpoint. Dissection was then
      performed to examine for complete release of the coracohumeral ligament and to
      assess the structures at risk of injury. RESULTS: The distance from the anterior
      edge of supraspinatus to the superior edge of subscapularis at the glenoid rim
      was 21.6 mm, which increased to 27.8 mm with joint distention. The minimum
      distance from the rotator interval to the deep surface of the coracoid process
      was 11.4 mm. Before distention, the coracoacromial ligament was an average of 6.2
      mm from the rotator interval capsule. Arthroscopic release from the supraspinatus
      to the subscapularis resulted in complete resection of the coracohumeral ligament
      in all 15 specimens. There were no specimens with evidence of injury to the
      biceps tendon, supraspinatus, subscapularis, or the conjoint tendon. CONCLUSIONS:
      This study confirms that intra-articularly directed arthroscopic release of the
      rotator interval can safely lead to complete release of the coracohumeral
      ligament if dissection is taken superficially to the level of the coracoacromial
      ligament.

PMID- 11830808
TI  - Prospective analysis of radiofrequency versus mechanical debridement of isolated
      patellar chondral lesions.
AB  - PURPOSE: Debridment is used to treat Outerbridge grades 2 and 3 lesions in a
      mechanically aligned and properly tracking patella. It removes fibrillation and
      provides a stable rim of chondral tissue. Recent basic science reports suggest
      that radiofrequency probes are superior to mechanical shavers for articular
      cartilage debridement. The goal of this study was to compare the clinical
      outcomes of debridement of patellar grade 2 and 3 chondral lesions using
      radiofrequency and mechanical devices. TYPE OF STUDY: Patients were prospectively
      randomized into 2 treatment groups. METHODS: Consecutive female patients
      undergoing arthroscopy for symptomatic, isolated patellar cartilage lesions
      without evidence of instability, malalignment, or patellar tracking dysfunction
      were prospectively randomized into radiofrequency and mechanical debridement
      groups based on medical record number. All patients had failed a 6-month course
      of conservative treatment and had chondral pathology documented by magnetic
      resonance imaging. Patients were assessed before and after surgery using the
      Fulkerson-Shea Patellofemoral Joint Evaluation Score. RESULTS: Nineteen patients
      (mean age, 37.5 years) underwent chondral debridement using a mechanical shaver
      and 20 patients (mean age, 36.9 years) underwent chondral debridement using a
      bipolar radiofrequency probe at nonablative energy levels. The mechanical group
      had a mean preoperative score of 59.2 and the radiofrequency group had a mean
      preoperative score of 59.6. Postoperative scores at 12-month follow-up were 80.0
      for the mechanical group and 87.9 for the radiofrequency group (P =.0031). At 24
      months, the mean score of the mechanical group was 77.5 and the mean of the
      radiofrequency group was 86.6 (P =.0006). CONCLUSIONS: This study presents clear
      evidence of superior clinical outcome of debridement of patellar grade 2 and 3
      chondral lesions with the use of bipolar radiofrequency versus a mechanical
      shaver.

PMID- 11830809
TI  - Arthroscopic-assisted percutaneous screw fixation of select patellar fractures.
AB  - PURPOSE: To describe a technique of arthroscopic-assisted reduction and
      percutaneous cannulated screw fixation for displaced patellar fractures and to
      present the results of 5 cases. TYPE OF STUDY: Case series. METHODS: Five
      patients (3 male, 2 female) with displaced patellar fractures treated with an
      arthroscopic-assisted reduction and percutaneous cannulated screw fixation were
      prospectively analyzed. The mean age was 53 years (range, 27 to 74 years). All
      fractures were fixed with at least 2 4-mm cannulated screws under arthroscopic
      visualization. Cerclage wiring through the cannulated screws was necessary in 2
      patients with osteopenic bone. Controlled passive range of motion exercises were
      started on the first postoperative day. Full weight bearing with an immobilizer
      type brace was allowed as tolerated. The mean follow-up was 28 months (range, 24
      to 35 months). The patients were evaluated with Lysholm II scores, clinical
      examination, knee range of motion, thigh circumference measurements, and
      radiographs. RESULTS: All fractures healed uneventfully. The mean Lysholm II
      score was 84.8 (range, 75-96). All but 1 patient regained full knee range of
      motion. A mean quadriceps atrophy of 0.8 cm compared with the contralateral side
      was seen in unilateral cases. There was no implant failure or infection.
      CONCLUSIONS: Arthroscopic-assisted reduction and percutaneous cannulated screw
      fixation is appropriate for displaced transverse patellar fractures without major
      separation and comminution. Longitudinal or oblique fractures, even if there are
      more than 2 major fragments, are amenable to arthroscopic techniques, providing
      the fragments are large enough to be fixed with screws. This technique is
      minimally invasive and does not disturb the vascular supply of patella. It allows
      clear visualization of the reduction and stability of the fracture, and
      facilitates early postoperative range of motion exercises. This method is not
      suitable for highly comminuted fractures or transverse fractures with major
      separation that are accompanied by rupture of the extensor mechanism.

PMID- 11830811
TI  - Motion complications after arthroscopic repair of anterior cruciate ligament
      avulsion fractures in the adult.
AB  - PURPOSE: To investigate the risks involved in arthroscopic reduction of anterior
      cruciate ligament avulsion fractures in adults. TYPE OF STUDY: Retrospective case
      series. METHODS: We retrospectively reviewed the outcome of 17 adults treated
      arthroscopically for displaced anterior cruciate ligament avulsion fractures. All
      patients were treated with primary repair of the avulsion fragment using
      nonabsorbable sutures passed through the ligament base and pulled down through
      arthroscopically placed drill holes. Patients were evaluated an average of 5.4
      years (range, 2 to 9 years) after surgery. RESULTS: Of the 17 patients in this
      investigation, 9 (53%) had severe difficulty regaining motion postoperatively.
      Four patients (24%) required multiple arthroscopic debridements for lysis of
      arthrofibrotic scar tissue around the anterior aspect of the knee, 4 additional
      patients (24%) required manipulation under anesthesia to help regain motion, and
      1 patient declined manipulation despite significant motion complications. An
      additional 3 patients (18%) required a second arthroscopy for reasons including
      removal of loose bodies, anterior scar impingement, and removal of hardware. Only
      5 patients (29%) progressed through physical therapy uneventfully. CONCLUSIONS:
      Arthroscopic reduction of avulsion fractures of the anterior cruciate ligament
      was frequently associated with motion complications and often required additional
      surgical procedures. Adult patients who undergo this procedure should be
      counseled regarding the increased risk of motion complications.

PMID- 11830810
TI  - A study of retrieved allografts used to replace anterior cruciate ligaments.
AB  - PURPOSE: The purpose of the study was the examination of retrieved whole anterior
      cruciate ligament (ACL) replacement grafts to determine the rate and the extent
      of cellular replacement and remodeling of the grafts. TYPE OF STUDY: Gross and
      histopathologic examination of specimens. METHODS: Nine specimens of ACL
      replacement allografts and 1 autograft were obtained at autopsy and surgical
      procedures. RESULTS: Examination of these specimens from 20 days to 10 years
      after transplantation revealed a pattern of revascularization similar to that
      reported in previous biopsy studies. However, examination of the entire
      allografts showed that, at 2 years after transplantation, the central portions of
      the grafts remained acellular and that complete attachment was not present, but
      was found in a 3.5-year post-transplantation specimen. CONCLUSIONS: Because
      attachment of the graft to bone tunnel walls required over 2 years, the tunnel
      remodeling may be explained on a mechanical basis. The remodeling of ACL
      replacement grafts is a gradual or slow process. Complete remodeling and cellular
      replacement of the entire graft may require 3 years or longer.

PMID- 11830812
TI  - Rotational muscle strength of the limb after anterior cruciate ligament
      reconstruction using semitendinosus and gracilis tendon.
AB  - PURPOSE: To investigate the influence of harvesting semitendinosus and gracilis
      tendons on the rotational muscle strength of the limb after anterior cruciate
      ligament (ACL) reconstruction. TYPE OF STUDY: Prospective study. METHODS: We
      performed a prospective study of 62 consecutive (34 male, 28 female) patients
      with ACL reconstructions using the semitendinosus and gracilis tendons. The mean
      age at surgery was 20.8 years. The semitendinosus tendon was harvested in 32
      patients (ST group), and semitendinosus and gracilis tendons in 30 patients (STG
      group). The peak isokinetic torques for extension, flexion, internal rotation,
      and external rotation were measured before and 12 months after ACL reconstruction
      using the Cybex 6000B system (Cybex Division of Lumex, Ronkonkoma, NY). The
      rotational torque was measured at 30 degrees/sec and 120 degrees/sec. RESULTS:
      Before reconstruction, the mean isokinetic peak torque of the involved limb was
      decreased in extension and internal rotation. The mean isokinetic peak torque of
      the involved limb in extension recovered 12 months after ACL reconstruction;
      however, the weakness in internal rotation persisted. The preoperative weakness
      of the involved limb in extension and internal rotation recovered in the male
      patients, but not in the female patients after postoperative rehabilitation. The
      peak torque of the involved limb in internal rotation was decreased in the STG
      group, but not in the ST group. CONCLUSIONS: The internal rotational torque was
      influenced by harvesting the semitendinosus and gracilis tendons after ACL
      reconstruction, especially in female patients and patients from whom the gracilis
      tendon was harvested. Semitendinosus and gracilis tendons are important for the
      internal rotation of the limb and it was difficult to compensate for this
      function. Thus, we recommend harvesting the semitendinosus tendon only if tendon
      quality is sufficient to further minimize harvesting morbidity.

PMID- 11830813
TI  - Arthroscopic partial and total meniscectomy: A long-term follow-up study with
      matched controls.
AB  - PURPOSE: The purpose of this study was to compare the clinical and radiographic
      outcome of arthroscopic partial and total meniscectomy. TYPE OF STUDY:
      Retrospective outcome study. METHODS: Thirty-six male patients with stable knees,
      no previous knee injury, and arthroscopic meniscectomy were matched into 2
      groups: partial or total. In addition, a group of individuals with no known
      history of knee injury was matched to each patient with meniscectomy. All
      patients were re-examined by a clinical and radiographic examination 14 years
      after surgery. RESULTS: At follow-up, radiographic changes, including Fairbank
      changes and joint space narrowing, were seen in 6 of 18 patients (33%) after
      partial meniscectomy and in 13 of 18 patients (72%) after total meniscectomy (P
      <.05). Joint space narrowing >50% of the joint space was seen in 1 patient after
      partial meniscectomy but was present in 7 patients after total meniscectomy. In
      the healthy controls, 4 of 36 patients (11%) had radiographic changes but none
      had joint space narrowing. Fourteen years after surgery almost 70% of patients
      had a Lysholm score >94 (i.e., normal). Only 5 of 36 patients (14%) in the total
      meniscectomy group had knee symptoms during activities of daily living. A similar
      decline in activity levels according to Tegner was seen over time in the control
      group and in the 2 meniscectomy groups. CONCLUSIONS: The frequency of
      radiographic changes 14 years after meniscectomy is related to the size of the
      meniscus removed, but the grades of these changes are low and have little
      influence on activity and knee function.

PMID- 11830814
TI  - The effectiveness of the use of electrocautery with chondroplasty in treating
      chondromalacic lesions: A randomized prospective study.
AB  - PURPOSE: To determine the clinical effect of electrocautery with arthroscopic
      chondroplasty on chondromalacic tissue. TYPE OF STUDY: A randomized, prospective
      study. METHODS: In a prospective study, 146 patients were randomly placed in
      either a control group (chondroplasty alone) or a treatment group (chondroplasty
      and electrocautery). Intraoperative findings in both treatment and control groups
      were classified by both the extent of chondromalacia and the number of
      compartments in which chondromalacia was diagnosed. In our study, we used 6
      defined compartments: medial and lateral tibial plateau, medial and lateral
      femoral condyles, patella, and femoral trochlea. Patients were followed up at 1
      year and evaluated using the Lysholm scale. Postoperative Lysholm scores were
      matched against compartment involvement and compared between groups. RESULTS:
      There was no significant difference in the patients with grade 2 chondromalacia
      in either control or cautery group (P >.5). Groups with grade 3 chondromalacia
      showed a significant difference favoring the control group (P <.05). A
      significant difference was found in comparing 2-compartment chondromalacia
      between the 2 treatment cohorts, again, favoring the control group (P =.01). The
      remaining groups of multiple compartment chondromalacia showed no significant
      difference, indicating that the postoperative result was independent of the use
      of electrocautery. CONCLUSIONS: This study shows that electrocautery as an
      adjunct to chondroplasty offers little benefit in the treatment of chondromalacic
      lesions and may, in fact, limit successful outcome.

PMID- 11830815
TI  - The effect of strand configuration on the tensile properties of quadrupled tendon
      grafts.
AB  - PURPOSE: To compare selected biomechanical properties of 4 different quadrupled
      tendon graft preparations applicable for anterior cruciate ligament
      reconstruction. TYPE OF STUDY: Biomechanical investigation in a cadaver model.
      METHODS: Graft strands were arranged in parallel, braided, bolo-plait, and twist
      configurations. Elongation of the graft was monitored during loading with an
      infrared optical measurement system, which measured the 3-dimensional position of
      twelve spherical reflective markers mounted within the camera field. Permanent
      elongation, stiffness, and ultimate strength of each graft configuration were
      determined. RESULTS: Permanent graft strain after the first incremental loading
      cycle was 7.2% in braid, 6.6% in twist, 6.5% in bolo-plait, and 3.3% in parallel
      constructs (P <.0001). Permanent graft strain after a second incremental loading
      cycle was 1.2% in bolo-plait, 1.1% in braid, 0.7% in twist, and 0.7% in parallel
      preparations (P =.0012). Braid and bolo-plait grafts were less stiff than twist
      or parallel grafts (P <.0001). Differences in failure load were not significant
      (P =.171). CONCLUSIONS: Variation in graft configuration from the conventional,
      parallel strand pattern lead to increased viscoelasticity and permanent
      elongation of grafts with repetitive loading. This deficit is expected to cause
      increased laxity of the reconstructed knee.

PMID- 11830816
TI  - Comparison of knee magnetic resonance imaging findings in patients referred by
      orthopaedic surgeons versus nonorthopaedic practitioners.
AB  - PURPOSE: To compare the percentages of normal magnetic resonance imaging (MRI)
      examination results and clinically significant knee abnormalities in patients
      referred for MRI of the knee by orthopaedic surgery residents and staff with
      those of patients referred by nonorthopaedic practitioners. TYPE OF STUDY:
      Retrospective review of MRI findings. METHODS: MRI reports of 754 patients (454
      men and 300 women) were retrospectively reviewed; 373 patients were referred from
      the Department of Orthopaedic Surgery and 381 patients were referred from
      nonorthopaedic practitioners. The number of normal examination results, meniscal
      and ligament tears, chondral abnormalities, and Baker's cysts was tabulated and
      analyzed using a X-square injury analysis. RESULTS: The rate of normal results
      for nonorthopaedic practitioners was 33.9% (129 of 381) compared with 15.3% (57
      of 373) for orthopaedic surgeons (P <.001). Nonorthopaedic surgeons referred
      69.4% (129 of 186) of the patients who had normal examination results. The
      positive finding for a lateral meniscus tear was 29.2% (109 of 373) for
      orthopaedic surgeons compared with 19.1% (73 of 381) for nonorthopaedic
      practitioners, which was statistically significant (P =.002) in regard to the
      distribution of injuries. No difference was found in other abnormalities
      assessed. CONCLUSIONS: Patients referred by nonorthopaedic practitioners had
      significantly more normal knee MRI examination results than did those referred by
      orthopaedic surgeons.

PMID- 11830817
TI  - Use of a Caspari suture punch to repair a radial tear of the lateral meniscus.
AB  - SUMMARY: Radial meniscal injuries in young patients are challenging problems. A
      technique not previously described in the literature is presented for radial
      meniscal repair. A Caspari suture punch is used to repair the inner leaf of the
      radial tear followed by standard inside-out augmentation with zone-specific
      cannulas and No. 2.0 PDS suture. This technical note describes the technique and
      its result in a case report.

PMID- 11830818
TI  - A method for all-inside arthroscopic repair of Palmer 1B triangular
      fibrocartilage complex tears.
AB  - There have been different descriptions of arthroscopic repair of the Palmer 1B
      tear of the triangular fibrocartilage complex (TFCC). Both outside-in and inside
      out techniques are in common use, but both have the disadvantage of an extra
      incision to tie the knots and they are time consuming. We present a technique for
      all-inside repair of Palmer 1B TFCC tears using a technique known from meniscal
      repair in the knee joint.

PMID- 11830819
TI  - Chronic posterolateral instability of the knee: A new surgical approach.
AB  - Posterolateral instability of the knee joint is known to be one of the most
      disabling injuries of the knee. Despite the surgeon's efforts, it often remains
      unrecognized in the acute phase. Although many techniques have been described to
      treat it, there are still controversies about the results, and sometimes it is
      difficult to use them in every case. We present a technique using the
      semitendinous while preserving the distal insertion to make both passive and
      active reinforcement of the damaged structures.

PMID- 11830820
TI  - Arthroscopic transhumeral rotator cuff repair: Giant needle technique.
AB  - An arthroscopic transhumeral rotator cuff repair technique is presented with
      which the same type of cuff repair can be performed as with an open standard
      procedure. After adequate arthroscopic subacromial decompression, a bone trough
      is made on the greater tuberosity and a hole is punctured with a sharp hook. A
      special bone-cutting needle with a suture (giant needle) is then passed through
      the skin and deltoid muscle in front of the acromion, through the torn tendon,
      the hole in the trough, and out through the lateral cortical surface through the
      deltoid and skin. The suture limbs are pulled out through the instrumentation
      portal and a sliding knot is made to close the defect. No hardware implants are
      used and the procedure is not technically complicated. During surgery only two
      thirds of the steps used for open repair were required. With experience, a large
      tear was repaired as well as with an open repair. The advantages of this
      technique are that the strength of cuff fixation does not rely on the quality of
      the bone in the greater tuberosity, there is no need for complicated suture
      passing techniques through the rotator cuff, and it offers the same fixation
      technique as the traditional open repair.

PMID- 11830821
TI  - Arthroscopic retrieval of an unusual foreign body of the knee.
AB  - We report an unusual use of the arthroscope in the case of a man who accidentally
      shot himself through his left thigh, the bullet ending up in the ipsilateral knee
      joint. After radiographic diagnosis, the bullet was successfully removed through
      a standard arthroscopic procedure. The patient had a quick and complete recovery.
      Review of the literature and the 4 steps of successful management of gunshot
      wounds are included.

PMID- 11830822
TI  - Chronic synovitis caused by a date palm thorn: An unusual clinical picture.
AB  - Synovitis related to plant thorns is a rare pathology. As in this case, thorn
      prick injury, which is particularly caused by thin palm thorns, is frequently
      missed in clinical history. Clinical presentation of cases may simulate juvenile
      rheumatoid arthritis with monoarticular involvement and septic arthritis. Removal
      of all thorns with partial or total synovectomy is essential in definitive
      treatment. Arthroscopy is the most valuable method of meeting both diagnostic and
      therapeutic purposes as it provides the best visibility of the joint with lower
      morbidity.

PMID- 11830823
TI  - Two cases of tibial nerve compression caused by uncommon popliteal cysts.
AB  - We report 2 cases of a popliteal mass of very unusual origin that induced
      compression neuropathy. The signs and symptoms could have been mistaken for those
      of a common Baker's cyst. Several recent studies have shown that the cause of
      Baker's cyst formation should be sought within the joint because of a
      communication between the gastrocnemio-semimembranosus bursa and the joint
      cavity. These 2 cysts had no communication with the articular joint, thus
      suggesting that the surgeon perform an open exploration of the popliteal fossa in
      the search for other cystic formations with origins and features different from
      Baker's cysts.

PMID- 11830824
TI  - Observation of anomalous insertion of the medial meniscus on the anterior
      cruciate ligament.
AB  - We wanted to determine the frequency of occurrence and types of anomalous
      insertions of the medial meniscus to the anterior cruciate ligament (ACL) in
      Finnish patients. In 987 consecutive arthroscopies from January 1996 to August
      1998, the meniscal pathology was mapped using videoprints and drawings. We found
      11 anomalous medial meniscus insertions to the ACL. There were 4 female and 6
      male patients in the series. In 1 woman, the anomaly was bilateral. The mean age
      of the patients was 30.6 years (range 14 to 63 years). The anomalous band was
      excised in all patients. The anomaly usually was not the finding that caused the
      need for arthroscopy. In 3 knees, the anomaly was the only pathologic finding.
      The frequency of this anomaly occurring was approximately 1.2%. The anomalous
      medial meniscus insertion to the ACL is a very rare clinical finding.
      Arthroscopic surgeons should be aware of its existence as well as of other
      anterior horn insertion variations of the medial meniscus.

PMID- 11830825
TI  - New insights into the pathogenesis of intestinal dysfunction: secretory diarrhea
      and cystic fibrosis.

PMID- 11830826
TI  - [Adhesive dentistry. Possibilities for improving esthetics in the periodontally
      treated patient].
AB  - Periodontal treatments frequently result in a further recession of the gingiva,
      thereby introducing esthetic problems. The newest adhesive techniques and resin
      composites are extremely suitable to make esthetic restorations which can improve
      the esthetics of the dentition. In this article several treatments, based on
      adhesive techniques, are demonstrated and discussed.

PMID- 11830827
TI  - [HIV and dentistry. Part 6. Mouth defects in HIV infections: guidelines for
      referral].
AB  - As for any oral lesion that cannot be properly diagnosed by the dentist, referral
      to the specialist is indicated for lesions that might be associated with or
      indicative of an underlying HIV infection. In most instances, there is no need to
      discuss the subject of HIV infection in the dental office. In the letter of
      referral the same information should be given as has been provided to the
      patient. The specialist should not withhold information for the referring
      dentist, even when requested by the patient to do so.

PMID- 11830828
TI  - [Amalgam. XV. Electrochemical activity in the mouth].
AB  - Almost all metals used in dentistry can corrod. The uniform corrosion is not so
      important in concern to the used metals. This type of corrosion may become
      important in an extreme environment with the low pH which can exist in plaque,
      denture adhesive and fluoride gel. An important type of corrosion is contact
      corrosion, which results in a higher corrosion rate of the base metal in the
      galvanic couple noble-base metal. As a result of the small io (exchange current
      dentistry) the higher corrosion rate is the result of a larger reaction surface
      for the reduction reaction. Another important type of corrosion is caused by
      differences in the surface. As a result of this differentiation pitting or
      crevice corrosion may occur. Also bacteria and other micro-organisms can have an
      influence on the corrosion process. The corrosion rate is not only determined by
      the redoxpotential but also by other factors.

PMID- 11830829
TI  - [Anxiety disorders in the dental practice. Part 2. Treatment of patients with
      anxiety].
AB  - The purpose of the present paper is to provide the dentist with a number of
      treatment steps that may reduce anxiety and may enhance trust, feelings of
      control and application of coping skills. A distinction should be made between
      patients with specific fear for one or more aspects of dental treatment and
      patients with non-specific, general anxiety. Practical implications for dental
      treatment of both groups are given. Dentists should be familiar with the signs
      and symptoms of the various anxiety disorders, in order to be able to properly
      refer or treat the patient.

PMID- 11830830
TI  - [Denturists and the Occupations in Individual Health Care Law].
AB  - The legal position of denturists in the Netherlands will be discussed again in
      the near future. At the moment it is uncertain what the legal basis will be. It
      is important for denturists and other dental professionals to investigate the
      different possibilities in the legislation. Historical research and research of
      sources of law concerning the development of denturism learned that denturists
      have a lot of arguments to obtain a solid position in future legislation.

PMID- 11830831
TI  - [Multiple periapical radiolucency].

PMID- 11830832
TI  - [Diagnosis of primary caries. Current techniques and their consequences for
      treatment].
AB  - The decline in caries prevalence in The Netherlands has incited dentists to focus
      their attention to the detection of small carious lesions rather than large
      cavities. The diagnosis of primary caries is, however, still predominantly being
      accomplished by the traditional diagnostic methods, used in the high caries
      prevalence era. Today's appearance and behaviour of caries lesions have led to
      the situation that incipient enamel lesions, dentinal caries and cavities are
      frequently missed during routine recall examinations. There is increasing concern
      with the occurrence of large caries lesions underneath visually intact enamel.
      These problems have induced diagnostic research aimed at developing and
      evaluating new caries diagnostic methods and some of them are already used in
      general practice. Visual inspection and bitewing radiography, however, still
      constitute the most important methods in the diagnosis of primary caries. The
      results from these examinations are used to classify an individual's caries risk,
      to monitor the progression of existing caries lesions, and to aid preventive or
      restorative treatment decision making.

PMID- 11830834
TI  - [HIV and dentistry. Part 10. Concluding remarks].
AB  - In a summarizing report of the series 'HIV and dentistry' the most important
      aspects of the dental treatment of HIV-seropositive patients are dealt with,
      supplemented with some additional comments.

PMID- 11830833
TI  - [Amalgam. XIX. Final: a reply to opponents and some guidelines].
AB  - Opponents of the use of dental amalgam fillings often hold specific views on
      health and illness. Their doubts about the safety of amalgam are based upon
      unproven theories and results obtained with invalidated diagnostic methods and
      case-histories. It is contended here that case-histories cannot be accepted as
      scientific evidence and do not warrant over-simplified and idle, yet threatening
      statements. Almost superfluously, the improbability (not identical to
      impossibility!) of toxic symptoms and the rare manifestation of allergic
      reactions are summarized, prior to the description of some measures to diminish
      the release of mercury from amalgam restorations. Guidelines are presented how to
      deal with patients with health complaints attributed by them to amalgam.

PMID- 11830835
TI  - [Guidelines for occlusions and articulation. Part 2. Crown and bridgework on
      dental implants].
AB  - It is generally accepted that one should minimize horizontal forces or horizontal
      components of more vertically directed forces when loading dental implants. This
      has its implications for the choice of the occlusion concept. In this article
      various occlusal concepts aimed at different types of fixed prostheses on dental
      implants are discussed. When possible canine guided articulation or group
      function must be strived for. It is stressed that detailed pre-implantological
      diagnostics and treatment planning are essential to achieve high treatment
      standards.

PMID- 11830836
TI  - [How sensible are bacteriological tests in periodontology?].
AB  - Periodontitis is a mixed infection with subgingival bacteria that belong to the
      microflora of the host. The bacteriological tests (Microscopy, Culture, Omnigene,
      Affirm DP and Evalusite) are mainly aimed at spirochetes or A.
      actinomycetemcomitans, P. gingivalis and P. intermedia. The detection limits of
      the different tests vary and, therefore, the detection levels are between 0.01
      10% of the subgingival microflora. However, threshold levels to distinguish
      between diseased and carrier state are not established and the low sensitivity
      and specificity of the tests limit their diagnostic usefulness. The correlation
      between the tested bacteria and periodontitis does not mean a causal
      relationship. As a result, the justification of the elimination of the tested
      bacteria is questionable. The tests of the subgingival plaque do not only add to
      the microbiological knowledge, but might also promote the overtreatment with
      antibiotics, such as the in the Netherlands popular combination of amoxicilline
      and metronidazole. The balance between host and microflora can be restored in
      most patients by mechanical elimination of the mainly Gram negative anaerobic
      subgingival plaque. In special occasions metronidazole can be empirically
      prescribed in order to support the subgingival debridement. In the relatively
      rare occasions of superinfection, a sensitivity test of the subgingival
      microbiota is recommended.

PMID- 11830837
TI  - [Antibiotics and dentistry].
AB  - The prescription of antibiotics in the dental office should be balanced against
      the possible side effects. For prophylactic use in selected cases, advice is
      given with regard to the choice of the antibiotics, the oral dosage and the time
      period.

PMID- 11830838
TI  - [Erythema of the mucosa of the roof of the mouth].

PMID- 11830839
TI  - [Hormone replacement therapy and breast cancer--any news?].

PMID- 11830840
TI  - [Critical illness polyneuropathy].

PMID- 11830842
TI  - [Where did the blood cells vanish?].

PMID- 11830841
TI  - [Suicides in the elderly in Finland].

PMID- 11830843
TI  - [Tetanus].

PMID- 11830844
TI  - [Citation and impact factors--a master or a farm-hand?].

PMID- 11830845
TI  - [Treatment recommendations for benign prostate hypertrophy].

PMID- 11830846
TI  - [Heart surgery in the next millennium].

PMID- 11830847
TI  - [Can heart diseases in the elderly be treated with surgical means?].

PMID- 11830848
TI  - [Changed timing of heart valve operations].

PMID- 11830849
TI  - [Reconstructive surgery of mitral valve].

PMID- 11830850
TI  - [New heart valve prostheses].

PMID- 11830851
TI  - [Correction of the aortic valve without a prosthesis].

PMID- 11830852
TI  - [Coronary artery bypass grafting using arteries as grafts].

PMID- 11830853
TI  - [Minimal-access surgery in the treatment of coronary artery disease].

PMID- 11830854
TI  - [Transmyocardial laser revascularization].

PMID- 11830855
TI  - [Surgical treatment of arrhythmias].

PMID- 11830856
TI  - [Bisphosphonates inhibit matrix metalloproteinases--a new possible mechanism of
      action].

PMID- 11830857
TI  - [Bisphosphonates in the therapy of cancer patients].

PMID- 11830858
TI  - [Antidepressant agents in the therapy of severe depression in adolescents].

PMID- 11830859
TI  - [Use of statistical methods and their possibilities in clinical quality
      improvement].

PMID- 11830860
TI  - [Duodecim journal now on the internet:http://www.duodecim.fi].

PMID- 11830861
TI  - [Sarcoidosis in an infant].

PMID- 11830862
TI  - [Penile fracture].

PMID- 11830863
TI  - [Treatment of enuresis].

PMID- 11830864
TI  - [Sonohysterography--a new method to diagnose gynecological bleeding disorders].

PMID- 11830865
TI  - [The research group gets a new member--a possibility to the better or a source of
      problems?].

PMID- 11830866
TI  - [Only a few will gain from estrogen level determinations in connection to the
      follow-up of hormonal replacement therapy in menopause].

PMID- 11830867
TI  - ["White coat" hypertension has to be treated].

PMID- 11830868
TI  - [Smoking and nicotine dependence].

PMID- 11830869
TI  - [Neuropeptide Y and serum cholesterol].

PMID- 11830870
TI  - [The efficacy of psychological debriefing].

PMID- 11830871
TI  - [Chlamydiaceae and cancer].

PMID- 11830872
TI  - [Hereditary angioneurotic edema].

PMID- 11830873
TI  - [Joint meetings as a part of quality assessment on a psychiatric acute ward].

PMID- 11830874
TI  - [Toxoplasma encephalitis in a previously healthy man].

PMID- 11830875
TI  - [The claw hand: first sign of a metabolic disease].

PMID- 11830876
TI  - [Diagnostics and therapy of nicotine dependence].

PMID- 11830877
TI  - [Therapeutic use of fluoroquinolones].

PMID- 11830878
TI  - [Obstetricians to "tailor" the births].

PMID- 11830879
TI  - [Does mother's experience endanger the child's wellbeing?].

PMID- 11830880
TI  - [On "tailored" childbirth and obstetrical pain].

PMID- 11830881
TI  - [Because of the previous letters].

PMID- 11830882
TI  - [Streptococcus or chlamydia?].

PMID- 11830883
TI  - [We got rid of the smallpox--will we get monkeypox instead?].

PMID- 11830884
TI  - [N-Acetylcysteine--a new possibility in the therapy of hepatic failure].

PMID- 11830886
TI  - [Mild cognitive impairment as an early sign of dementia].

PMID- 11830885
TI  - [N-Acetylcysteine: new possibilities to use an old substance].

PMID- 11830887
TI  - [Generalized pustular psoriasis during pregnancy: an effective treatment with
      cyclosporin].

PMID- 11830888
TI  - [Recurring meningitis in a patient with LED].

PMID- 11830889
TI  - [Drug therapy of multiple sclerosis].

PMID- 11830890
TI  - [Endoscopy of esophagus, ventricle and duodenum (gastroscopy)].

PMID- 11830891
TI  - [Future of scientific journals--will the main stream of information dry out the
      16000 creeks?].

PMID- 11830892
TI  - [The peer review system of articles should be developed further].

PMID- 11830894
TI  - [From research result to news].

PMID- 11830893
TI  - [Duodecim society's role in cherishing and developing the use of Finnish language
      in medicine].

PMID- 11830896
TI  - [Physician and mass media--a threat or a possibility?].

PMID- 11830895
TI  - [If media would happen to meet the doctor].

PMID- 11830897
TI  - [Gastroscopies in the elderly].

PMID- 11830898
TI  - [Adolescence--a challenge for the therapy of diabetes].

PMID- 11830899
TI  - [The use of video conference equipment in education and telepathology].

PMID- 11830900
TI  - [Men have smaller and more atherogenic LDL particles than women].

PMID- 11830901
TI  - [Immediate protamine sulphate allergy in an insulin-treated diabetic patient].

PMID- 11830902
TI  - [The actions of insulin].

PMID- 11830903
TI  - [Persistent fever and a solitary liver finding].

PMID- 11830904
TI  - [Neurobiology in the next millennium:challenges and dreams].

PMID- 11830905
TI  - [From brain functions to perceptions].

PMID- 11830906
TI  - [Brain as a model for future computers?].

PMID- 11830907
TI  - [Physiology of the biological clock and the relation of circadian rhythm
      disorders to illnesses].

PMID- 11830908
TI  - [Regeneration of nervous system--will the Superman fly again?].

PMID- 11830909
TI  - [Genes behind epilepsy and neurobiology].

PMID- 11830910
TI  - [Neurotrophic growth factors in the development and plasticity of nervous
      system].

PMID- 11830911
TI  - The effectiveness of an ionic toothbrush in the removal of dental plaque and
      reduction on gingivitis in orthodontic patients.
AB  - This investigation was undertaken to determine if an ionic toothbrush was
      effective at removing plaque and reducing gingivitis in patients wearing
      orthodontic appliances. Fifty-two orthodontic patients were randomly assigned to
      one of two groups and completed a six-week double-blind study. Group 1 consisted
      of the test group using the ionic toothbrush with an active battery; group 2
      consisted of the control group using the ionic toothbrush with an inactive
      battery. The plaque and gingival indices were measured at baseline, two weeks,
      and six weeks. The findings demonstrated that the active ionic toothbrush was no
      more effective at plaque removal and gingivitis reduction than the inactive
      toothbrush. Although the active toothbrush did effectively remove plaque and
      reduce gingivitis over the course of six weeks, it showed no significant
      improvement over the same toothbrush that contained an inactive battery. It was
      observed that the ionic toothbrush effectively reduced plaque and gingivitis
      regardless of the presence or absence of an active battery. The clinical findings
      demonstrated that an active ionic toothbrush was no more effective in removing
      plaque and reducing gingivitis in patients with orthodontic appliances than an
      inactive ionic toothbrush.

PMID- 11830912
TI  - Grafting of human epidermal cells, presence and perspectives.

PMID- 11830913
TI  - Conservative treatment of developmental dysplasia of the hip in Kuwait.
AB  - This paper evaluates the results of conservative treatment for developmental
      dysplasia of the hip after an average follow-up of 3 years in 69 patients and 99
      hips: 31 bilateral, 23 left side, and 14 right. They were treated at the Al-Razi
      Hospital, Kuwait, between January 1995 and December 1996. There were 59 girls and
      10 boys aged between 5 months and 24 months (average age 12 months). The
      treatment consisted of traction for 1 or 2 weeks, followed by manipulation in 36
      hips and manipulation with adductor longus tenotomy in 45 hips and with adductor
      longus and psoas tenotomy in 18 hips. Avascular necrosis of the femoral head
      developed in 16 hips (16%): 14 hips on the affected side and 2 hips on the
      unaffected side. Persistent acetabular dysplasia was present in 13 hips,
      subluxation in 9 hips and dislocation in 13 hips. Open reduction was later
      required in 5 hips, open reduction and innominate osteotomy in 8 hips, and hip
      extracapsular innominate osteotomy in 1 hip. The results were evaluated according
      to the age groups with highest rate of complications after the age of 15 months.
      The treatment protocol was changed to limit conservative treatment until the age
      of 14 months.

PMID- 11830914
TI  - Extracorporeal shock wave lithotripsy of gallstones with oral dissolution.
      Results in course of ten years in Czech Republic in correlation to indication
      criteria.
AB  - BACKGROUND/AIMS: We compared the results of treatment of gallbladder stones by
      extracorporeal shock wave lithotripsy with dissolution during two periods to
      different criteria of indication. In the first period (1990-1991) we treated
      patients with stones up to 3 cm in diameter. In the second period (1992-1994) the
      indication included stones up to 1.5 cm with gallbladder contraction on
      cholecystography, which was also quantitatively determined by USG exceeding 60%
      of fasting volume. METHODS: We used Czech made lithotriptors MEDILIT. The shock
      waves (SW) are produced by an underwater high voltage discharge and the
      concentration of SW is achieved by reflection. The localization of stones is
      performed by means of a sonographic probe. After stone localization usually 700
      SW are applied to a patient lying in prone position. Oral dissolution was started
      in both groups of patients two weeks before shock wave application.
      Ursodeoxycholic acid and chenodeoxycholic were administered in doses of 7.5 mg/kg
      body weight/day. RESULTS: In the first group of 260 patients (average age 42),
      which had moderate indication criteria, disappearance of fragments during one
      year was found only in 148 (57%). The remaining patients were treated
      symptomatically or recommended to cholecystectomy. In a second group of 160
      patients (average age 45), disappearance of fragments during one year was
      achieved in 125 (78%). We used stricter indication criteria and our results are
      much better compared to the first group. Only 208 patients from both groups were
      controlled for more 5 years, in 89 cases of this number was a recidivity of
      lithiasis and at 20 of them we indicated cholecystectomy, 22 of the patients
      refused to continue in the therapy, because the stones are asymptomatic.
      CONCLUSION: In our opinion, this therapy (ESWL combined with oral dissolution) is
      suitable in 7% patients with gallbladder stones. Its side effects are very small,
      practically negligible. It can be performed without general anaesthesia and on an
      out-patient basis. After the advent of laparoscopic cholecystectomy we observed
      diminished interest of both patients and their physicians for gallbladder ESWL,
      however, after it has reached a widespread use, a new interest in ESWL and
      dissolution therapy is emerging, which we attribute to its above-mentioned
      advantages.

PMID- 11830915
TI  - An absence of changes in kidney tissues after an enormous number of shock waves.
AB  - Repeated sessions of unilateral extracorporeal shock wave lithotripsy (ESWL) were
      performed in a patient with multiple bilateral calycolithiasis who suffered from
      Crohn's disease of long duration and from recurrent gastric ulcers. To achieve
      complete clearance of stones from the left kidney it was necessary to apply
      10,000 shock waves during seven sessions within five weeks. This number is
      exceedingly high compared to average total doses which were applied to other
      patients of our group (920 SW per one session). For the treatment was used an
      electrohydraulic lithotripter (Medipo). A surgical reconstruction of the
      abdominal wall which had been planned long before was made six weeks after the
      last ESWL session. The postoperative course was complicated by bleeding gastric
      ulcer of which the patient died despite an intensive treatment. The autopsy and
      histology revealed no damage of kidney tissue or adjacent organs caused by ESWL.

PMID- 11830916
TI  - [Effect on hemolysis by shock waves created by a new method of multichannel
      discharge].

PMID- 11830917
TI  - [Effect of shock waves on hip prosthesis implantation (preliminary report)].
AB  - Revision of total hip arthroplasty has increased dramatically and it began to be
      a big problem, because of the number of reoperation is growing directly with the
      number of primoimplantation. Extraction of bone cement from the canal of the
      femur is timely and technically very difficult and related with many
      complications. Therapy by ESWL was applicated in clinical praxis for the first
      time in the therapy of urolithiasis and then choledocholithiasis. Now it is used
      in orthopedy for the therapy of pseudoarthrosis, entesopathia and anthores. In
      our experiment we used models of pork femur to which we implanted the
      endoprothesis to bone cement. We expouned these samples to ESWL and controlled
      the ability of releasing of the endoprothesis. We replayed the experiment for
      four times after an abnormal number of shockwaves (more than 8,000 shocks), in
      two cases endoprothesis release spontaneously, in one case we needed a little
      power to release it and in the four cases the releasing was not achieved. These
      results show the probable influence of the shockwaves between the layers metal
      cement and cement-bone spongiosa.

PMID- 11830918
TI  - [Optimal therapy with erythropoietin (EPO) in patients with renal anemia on
      hemodialysis therapy].
AB  - Treatment of anaemia of renal origin by recombinant erythropoietin (EPO) is well
      established and is considered to be an integral part of therapy in patients with
      chronic renal failure. An open, non-controlled and multicenter study was designed
      with aim to verify the dosage of EPO, necessary to reach and maintain rational
      correction of renal anaemia in a representative group of patients in chronic
      haemodialysis (HD) treatment. Target range of haemoglobin (Hb) was defined to be
      100-120 g/l in adult patient, length of maintenance phase of follow-up 6 months.
      183 patients from z 8 HD centres were included to the study, in this number 83
      (45.4%) men and 100 (54.6%) women, aged 59.8 +/- 14.4 years (min. 20 and max. 87
      years). During the next 6 months haemoglobin levels raised from baseline value
      Hb0 100 g/l to Hb1 102.9, resp. Hb2-104.9, Hb3 106.1, Hb4 107.5, Hb5 108.2 and
      Hb6 108.1 g/l; while mean total weekly doses of EPO/kg (TWD/kg) in the respective
      period corresponded to TWD/kg0 62 IU, resp. TWD/kg1 66 IU, TWD/kg2 67 IU, TWD/kg3
      62 IU, TWD/kg4 64 IU, TWD/kg5 60 IU, TWD/kg6 56 IU. Clinical complications
      (inflammatory state, bleeding...) that could in different extent reduce the
      effectivity of EPO treatment were observed in 50 cases. No serious clinical
      complications that could be attributed to EPO treatment were found. On basis of
      results of our study, it is justified to assume that target range of Hb between
      100-120 g/l can be reached with relatively modest increase of EPO dosage in
      comparison to current praxis in HD centres in CR, and that following cautious
      dosing of EPO (comparable to the dosing schema in our study) the treatment should
      not be connected with the development of major clinical complications.

PMID- 11830919
TI  - [Evaluation of vascular access for hemodialysis using combined measurement of
      recirculation in normal and inverted needle placement and determination of blood
      flow through the access].
AB  - The article describes novel method of vascular access quality assessment by means
      of combined measurement of recirculation with normal and inverse needles
      placement and calculation of vascular access blood flow from the recirculation
      data. Blood flow values seen in a large group of patients ranged from as low as
      200 ml/min up to as high as 2 l/min. Females and diabetics exhibited lower values
      as compared to males and non-diabetics. The method enables to detect a number of
      anomalous sates which cannot be detected by conventional means based on
      monitoring of pressures or recirculation measurement at normal needles placement
      only (stenosis between both needles, uintentionally erroneous placement of
      needles in accesses with a loop). Assessment of access blood flow is suitable
      also for evaluation of interventions on the access, such as percutaneous
      transluminal angioplasty or surgical narrowing of anastomosis in case of too high
      blood flow.

PMID- 11830920
TI  - [Tamoxifen or tamoxifen in combination with chemotherapy in adjuvant therapy of
      breast carcinoma. Results of a multicenter randomized study].
AB  - Between April 1994 and May 1997 103 breast cancer patients (pts), pT1c-3a, pN0-1,
      M0, were randomised after surgery to adjuvant tamoxifen (20 mg per day) or to
      tamoxifen plus CMF (C 500 mg/m2, M 40 mg/m2 and F 600 mg/m2 on days 1st and 8th q
      28 day) in 6 cycles. The median age (49-72 years, median 58), tumour size, number
      of involved lymphnodes (0-3), estrogens receptor status, grade (I-III) and type
      of operation were well balanced among the 50 pts on tamoxifen and the 53 pts on
      tamoxifen plus CMF pts, preferably postmenopausal. RESULTS: Grade of toxicity
      according to WHO criteria was not higher then two in both arms. Toxicity both
      haematological and non-haematological was higher in the group treated with
      chemotherapy (0 vs 32 resp. 20%) except weight gain  (52% in both group). After
      median follow-up of 42 mos five recurrences in tamoxifen and seven in tamoxifen
      plus CMF pts were observed (p = NS). The projected 3-y DFS is 92% for tamoxifen
      and 88% for tamoxifen plus CMF (p = NS). The 3-y OS is 88% for tamoxifen and 80%
      for tamoxifen plus CMF pts (p = NS). CONCLUSIONS: Both regimens are equally
      effective with higher toxicity in the group with combined chemo- and hormonal
      therapy.

PMID- 11830921
TI  - Antiandrogenic activity of epitestosterone in male mice in vivo.
AB  - Steroidal antiandrogen epitestosterone was administered to intact male mice and
      its effect on seminal vesicles, kidney, femoral bones and circulating calcium,
      phosphate, testosterone and LH were compared with controls and castrated animals.
      Epitestosterone was previously reported as an inhibitor the binding of androgens
      to their receptors, an inhibitor of the formation of dihydrotestosterone from
      testosterone and a modulator of estradiol-estrone conversion. In the present
      study it is demonstrated that it decreased the weight of kidney, seminal vesicles
      and bone density, ash weight and calcium and phosphate content of femoral bone
      tissue significantly, although not to the values as low as those seen in
      castrated animals. Thus in mice epitestosterone effects could be classified as
      antiandrogenic.

PMID- 11830922
TI  - [Freely programmable automatic radioimmunoanalysis on the STRATEC ST 300
      analyzer].
AB  - We compared the free programmable automatic radioimmunoassay on analyser STRATEC
      SR 300 to the manual performance of RIA and IRMA. One-step and two-step methods
      were evaluated. Manual delivery proved to be faster than the automatic one. The
      speed of dispensing depends on the volume of the dose sample and of the reagent,
      on the adjustment of rinsing volumes of the needle, washing volumes among
      separate doses and also on the size of the sample set. The total efficiency of
      the manual and the automatic analysis is also affected by other operations,
      especially by washing test tubes and the administration of reports. For a set of
      100 analyses, the manual process is from 20 to 90 minutes longer than the
      automatic one, depending on the analytical method used. Thus, the automatic
      analysis proved to be significantly faster. Nor the comparison of isotope and non
      isotope immunoassays showed any relevant qualitative or quantitative differences
      in analytical response. At the same time the prices of radioimmunoassays are more
      favourable, and in addition to that, a big choice of analytical sets is available
      which are not dependent on the user's instrumentation. However, this does not
      concern very small series, or separate tests where size of calibration is
      important. Moreover, the turn-around-time of RIA and IRMA is in these cases
      longer than when automatic non-isotope methods are used.

PMID- 11830923
TI  - [Teaching of geriatrics and gerontology at medical schools].
AB  - Analysis of goals and approaches in teaching geriatrics and gerontology for
      undergraduate medical students according to literature and personal 6 years
      experience. A proposal of "two module model" with introductory module of general
      gerontology in first years of studium (stress on communication, reflection of the
      elderly as human beings, their limitations, risks, and needs, lectures for
      medical students as well as for students of nursing, occupational therapy and so
      on to support team approach). Advanced module of "proper medical geriatrics" in
      late clinical years of studium (to stress atypical character of diseases,
      investigation, differential diagnosis and importance of acute care for elders
      units).

PMID- 11830924
TI  - Carcinoma of the ampulla of Vater associated with other organ malignancies.
AB  - Because of its location with respect to the biliary system, carcinoma of the
      ampulla of Vater is considered to manifest earlier in its course of development
      than carcinoma of the pancreas. The most common physical finding is jaundice,
      which occurs in 93-100% of cases [1,2]. This retrospective study describes the
      results of the treatment and prognosis for double primary cancers in which cancer
      of the ampulla of Vater was associated with malignancies in other organs in 5
      patients who were diagnosed and treated at Kurume University Hospital. The
      patients included 5 men with an average age of 72.8 years. There were 3
      synchronous double and 2 metachronous double cancer patients. Regarding prognoses
      of these patients, 1 patient with associated lung cancer died because of
      postoperative complications after pneumonectomy, 1 patient died due to
      carcinomatosa peritonei developing from the ampulla Vater carcinoma, and 1
      patient died because of metastatic liver tumors from the ampullary carcinoma. In
      multiple cancers including ampulla Vater carcinoma, gastrointestinal cancers such
      as gastric or colon cancer occur frequently. Therefore, a careful
      gastrointestinal examination should be done preoperatively. We report our
      experience with 5 cases of ampullary carcinoma associated with malignancies in
      other organs and review the literature.

PMID- 11830925
TI  - The predictive value of p53, Ki-67 and angiogenetic factors in primary
      hypopharyngeal carcinoma.
AB  - To evaluate the predictive role of the oncogene p53, the proliferating marker Ki
      67, angiogenic factors platelet-derived endothelial cell growth factor/thymidine
      phosphorylase (PD-ECGF/dThdPase) and vascular endothelial growth factor (VEGF) in
      primary hypopharyngeal carcinoma, we immunohistochemically studied a series of 84
      primary hypopharyngeal carcinoma patients who were treated at the Department of
      Otolaryngology of Kurume University Hospital between 1990 and 1997. The
      correlation of each score according to the intensity and percentage of the
      labeled cells with the TNM stage, histological grade, metastasis and survival
      status was analyzed. The positive rate of p53 was 52.4%. The percentages of Ki-67
      labeled cells in patients with or without metastasis showed a significant
      difference (p = 0.011). VEGF also showed a significant difference between the
      live and death groups (p < 0.05) and also among the differentiation group (p <
      0.05). A statistically significant correlation was also seen between the score of
      Ki-67 and VEGF (r = 0.438, p < 0.001) or the score of Ki-67 and PD-ECGF (r =
      0.259, p < 0.001), respectively. In conclusion, the present study suggests that a
      correlation exists between proliferating and angiogenesis, and VEGF and Ki-67 are
      thus considered to be possible prognostic discriminators in hypopharyngeal
      carcinoma.

PMID- 11830926
TI  - Clinicopathological evaluation of surgical treatment for early gallbladder
      cancer.
AB  - We evaluated the therapeutic principles for early gallbladder cancer based on
      clinicopathological characteristics and outcomes in 27 patients encountered at
      the Kurume University Hospital between January, 1975 and December, 1999.
      Concerning the depth of wall penetration, 15 patients had mucosal cancers (m
      cancers), and 12 patients muscularis propria cancers(mp-cancers). The gross
      patterns were lp (pedunculated) in 16 patients, ls (sessile) in 3 patients, IIa
      (flat elevated) in 4 patients, and IIb (flat) in 4 patients. The operative
      procedure used was cholecystectomy (C) in 12 patients, 4 of whom underwent lymph
      node dissection. Full-thickness cholecystectomy (FTC) was carried out in 3
      patients, one of whom had lymph node dissection. Combination of C and gallbladder
      bed resection (GbBR) was performed in 7 patients, 6 of whom had lymph node
      dissection. Combination of C and bile duct resection (BDR), and lymph node
      dissection was performed in 1 patient. Combination of C and GbBR and BDR, and
      lymph node dissection was performed in 6 patients. All the patients who underwent
      lymph node dissection were negative for metastasis. Of the 27 patients, 2
      underwent laparoscopic operation: one with m-cancer was 79 years old, and the
      other with mp-cancer 86 years old. In the m-cancers, no lymphatic, venous or
      perineural infiltration was observed. In contrast, in the mp-cancers, lymphatic
      and venous infiltration each were observed in 4 patients (33.3%), although no
      perineural infiltration was observed. A diagnosis of gallbladder cancer was made
      postoperatively in 6 patients, of whom 4 had the IIb pattern and all were
      complicated by gallstone, indicating the difficulty of diagnosing the IIb
      pattern. The 5-year survival rates for the m- and mp-cancers were as high as
      90.9% and 80.8%, respectively. As a curative surgical technique for m- and mp
      cancers, lymph node dissection should be performed in addition to FTC, GbBR, and
      BDR, in combination. When a postoperative histopathologic diagnosis of
      gallbladder cancer has been made, no second-look operation should be performed
      for m-cancers, but lymph node dissection of up to the second group should be
      performed for mp-cancers in a second-look operation.

PMID- 11830927
TI  - Clinical study of severe influenza virus pneumonia that caused acute respiratory
      failure.
AB  - The mortality of the influenza virus pneumonia is on the increase caused by the
      decline of the vaccination for the influenza virus in Japan. The purpose of our
      research is to study the clinical feature of severe influenza virus pneumonia
      that caused acute respiratory failure. This study included 68 patients with adult
      influenza virus infection who consulted our hospital between October 1997 and May
      1999. Six (8.8%) of 68 were diagnosed as having influenza virus pneumonia that
      caused acute respiratory failure. All patients with influenza virus pneumonia
      showed severe conditions with respiratory failure and a high-risk group. Two
      super high age patients had emergency status with unconsciousness. A super high
      age patient with influenza virus pneumonia died of aspiration pneumonia 118 days
      after admission. All patients with influenza virus pneumonia were received
      antibiotics. Although 4 of 6 patients did not respond to antibiotics,
      adrenocorticosteroids were administered. As the result, 3 of 4 patients, healing
      was achieved. We concluded that adrenocorticosteroids might be useful for
      treating severe influenza virus pneumonia under the administration of appropriate
      antibiotics.

PMID- 11830928
TI  - Intraarterial corticosteroid infusion following radiotherapy for primary central
      nervous system lymphoma: feasibility and preliminary result.
AB  - To utilize the high lympholytic effect of corticosteroids with minimal systemic
      adverse effects, we used intraarterial corticosteroid infusion in the treatment
      of 8 patients with primary central nervous system lymphoma (PCNSL). One patient
      had recurrent PCNSL, while the other patients had primary disease. Following
      standard radiotherapy with or without some systemic or intrathecal chemotherapy,
      prednisolone (60-100 mg in total) or dexamethazone (12 mg in total) was rapidly
      infused through the carotid arteries in all patients and also through the left
      vertebral artery in 5 patients. No acute or late complications of this treatment
      were observed. All 8 patients achieved complete or partial response. Four
      patients died of the disease, while the other 4 were alive with (1 patient) or
      without (3 patients) disease at 8-37 months after treatment, giving a 2-year
      survival rate of 55%. Intraarterial administration of high-dose corticosteroids
      appears to be a feasible treatment modality. This method may be used in
      preradiotherapy setting to evaluate response of PCNSL in future studies.

PMID- 11830929
TI  - The effect of angiogenesis inhibitor TNP-470 against postoperative lung
      metastasis following removal of orthotopic transplanted human colon cancer: an
      experimental study.
AB  - We have investigated the antimetastatic effect of TNP-470 against postoperative
      lung metastasis following the removal of human colon cancer xenotransplanted into
      nude rat. The KM12SM human colon cells were injected into the cecal wall. At 5
      weeks after the injection, the cecum was removed including the tumor. Then, TNP
      470 was administered continuously by subcutaneous injection pump at a dosage of
      30 mg/kg/week. The Control Group received no administration of TNP-470. Group A
      and Group B received administration of TNP-470 just after the cecal removal for 4
      and 2 weeks, respectively. Group C received 2 weeks' administration of TNP-470
      from week 3 after the removal. The survival rate of each group was calculated,
      and any lung metastasis was evaluated macro and microscopically. At 7 weeks after
      the removal, lung metastasis was detected in all rats of the Control Group, and
      in 4 of 8 rats in Group C. In Groups A and Group B, only one rat developed lung
      metastasis. The 30 week-survival rate in Group A and that in Group B was
      significantly higher than that in the Control Group or Group C. Moreover, the
      incidence of lung metastasis at the time of death or 30 weeks after the removal
      in Group A, and in Group B, was lower than that in Control Group or Group C. The
      angiogenesis inhibitor, TNP-470 showed an excellent antimetastatic effect against
      postoperative lung metastasis from transplanted human colon cancer.

PMID- 11830930
TI  - Intrinsic factors involved in the depression of neuronal activity induced by
      temperature increase in rat hippocampal neurons.
AB  - The intrinsic factors involved in the temperature-dependent impairment of
      neuronal activity in hippocampal CA2-CA1 regions were investigated using optical
      recording techniques. At 32 degrees C, stimulation of the Schaffer collaterals in
      the hippocampal CA2 region evoked depolarizing optical responses that spread
      toward the CA1 region. The optical response was characterized by fast and slow
      components that were mainly related to the presynaptic action potentials and
      excitatory postsynaptic response, respectively. The increase of the temperature
      to 38 degrees C was associated with a reversible depression of the neuronal
      activity in the hippocampal brain preparations. The depression of neuronal
      activity was irreversible when the temperature was increased to 40 degrees C. In
      the presence of 22 mM glucose, the depression of the neuronal activity at 38
      degrees C was significantly attenuated. Pyruvate (22 mM), but not lactate (22
      mM), also improved the depression of neuronal activity induced by the temperature
      increase. Adenosine (200 microM) strongly depressed the excitatory postsynaptic
      response, but not presynaptic action potentials. 8-Cyclopentyl-1,3
      dimethylxanthine (8-CPT) (10 microM), an adenosine A1 receptor blocker,
      attenuated the adenosine-induced depression of the excitatory postsynaptic
      response. 8-CPT (10 microM) prevented the impairment of the excitatory
      postsynaptic response induced by the increase of the temperature to 38 degrees C.
      In contrast, the depression of presynaptic action potential at 38 degrees C was
      not prevented by 8-CPT (10 microM). N omega-nitro-L-arginine methyl ester (L
      NAME), a nitric oxide synthase (NOS) inhibitor, and methylcobalamin (10 microM),
      a vitamin B12 analogue, attenuated the inhibition of pre- and postsynaptic
      activities induced by the increase of the temperature to 38 degrees C.
      Glibenclamide, a KATP channel blocker, did not protect neuronal activity from the
      effects of the increase of the temperature. These results suggest that the heat
      induced depression of neuronal activity is mediated by multiple factors, such as
      impairment of energy metabolism and increase in extracellular adenosine and
      nitric oxide (NO) levels in hippocampal neurons.

PMID- 11830931
TI  - Total mesorectal excision, lateral lymphadenectomy and autonomic nerve
      preservation for lower rectal cancer: significance in the long-term follow-up
      study.
AB  - We clarify the significance of total mesorectal excision (TME), lateral
      lymphadenectomy (LLA), and of autonomic nerve preservation (ANP) compared to
      conventional surgery (CVS), for lower rectal cancer. All 458 patients curatively
      resected between 1962 and 1997 were retrospectively investigated. In Period I
      from 1962-1974, when CVS only was performed, in Period II from 1975-1984, TME or
      TME + LLA was performed, and in Period III from 1985-1997, TME + ANP, TME + ANP +
      LLA, or TME + LLA was performed. In Dukes A + B disease, there was no significant
      difference among the three periods, regardless of operation methods. In Dukes C
      disease, in Period I, CVS (42 patients: pts) had a local recurrence (LR) rate of
      45.2% and 5-year disease-free survival (5YDFS) rate of 33.3%. In Period II, TME +
      LLA (82 pts) had a lower LR rate of 26.8% (p = 0.0628) and higher 5YDFS 51.0% (p
      < 0.05) vs CVS. In Period III, TME + ANP (12 pts) had LR 25.0% and 5YDFS 55.6%,
      TME + ANP + LLA (45 pts) had LR 13.3% (p < 0.005, vs CVS) and 5YDFS 56.1% (p <
      0.01, vs CVS), and TME + LLA (18 pts) had LR 16.7% (p < 0.05, vs CVS) and 5YDFS
      20.8%. Also, CVS had the lowest curability rate 64.8% and the highest mortality
      rate 7.2%. TME and/or LLA was significant for reducing LR and improving survival
      in patients with Dukes C lower rectal cancer, compared to CVS. ANP was beneficial
      with LLA. TME + ANP was suitable for Dukes A or B disease.

PMID- 11830932
TI  - Xanthogranulomatous cholecystitis mimicking gallbladder cancer: report of a case.
AB  - A 61-year-old woman was admitted to our hospital with abnormal findings of
      abdominal computed tomography. Whereas she had neither fever nor abdominal pain,
      a cholecystitis was suspected. Ultrasonography showed a mass in the gallbladder
      with several stones, and an unclear border between the gallbladder and liver.
      Computed tomography showed a large-mass in the gallbladder with findings that
      seemed to indicate hepatic invasion and para-aortic lymph node metastasis. On the
      basis of these findings, we made a diagnosis of gallbladder cancer associated
      with hepatic invasion and lymph node metastasis. We treated this gallbladder
      tumor by hepatic arterial infusion chemotherapy via catheter with cisplatin and 5
      fluorouracil. Four weeks after administration of the anti-cancer drugs, the
      tumorous lesion of the gallbladder could not be detected by abdominal imagings,
      and the gallbladder wall revealed no irregular findings. During laparotomy, the
      gallbladder showed signs of chronic cholecystitis, and a cholecystectomy was
      performed. Findings of the resected specimens showed severe inflammation,
      fibrosis, and bleeding in the gallbladder wall with infiltration by many foamy
      cells. Histopathological diagnosis was xanthogranulomatous cholecystitis. We
      report here a case of xanthogranulomatous cholecystitis mimicking gallbladder
      cancer and review the literature.

PMID- 11830933
TI  - Advanced gastric cancer effectively treated by neoadjuvant continuous low-dosage
      5-fluorouracil and cisplatin (FP regimen): a case report.
AB  - We have experienced a case of advanced gastric cancer with para-aortic lymph node
      metastasis effectively treated by neoadjuvant continuous low dosage 5
      fluorouracil and cisplatin (FP regimen). The patient was a 67-year-old man
      diagnosed as having advanced gastric cancer type 4 with para-aortic lymph node
      metastasis. This patient was treated by continuous infusion of 5-fluorouracil (5
      FU) 500 mg/day, for 28 days, and infusion of cisplatin 10 mg/day over 1 hr on
      days 1-5, 8-12, 15-19, and 22-26. At 4 weeks later, a CT revealed that swelling
      in the para-aortic lymph node had disappeared, and the thickening in the stomach
      wall had diminished. This patient underwent a curative operation, and both the
      serum level of carcinoembryonal antigen (CEA) and carbohydrate antigen (CA 19-9)
      decreased to normal. These results suggested that the FP regimen was an effective
      neoadjuvant treatment for advanced gastric cancer with para-aortic lymph node
      metastasis.

PMID- 11830934
TI  - Laparoscopic ileus operation due to paracolostomy hernia.
AB  - We present a case report of a 62-year-old man with adhesive ileus caused by
      paracolostomy hernia. The patient underwent enterosynechotomy for ileus and
      colopexy for paracolostomy hernia laparoscopically. This procedure has benefits
      of prevention of recurrent adhesive ileus and early postoperative recovery of the
      intestinal tract.

PMID- 11830935
TI  - Long-term survival after gastric cancer with liver metastasis: a report of two
      cases.
AB  - We have experienced two cases of long-term survival after surgery for gastric
      cancer case with liver metastasis. One case was of a 66-year-old male patient
      diagnosed as having type 1 advanced gastric cancer located in the posterior wall
      of the lower body with liver metastasis. The stage of this case was P0H1N1T2M0
      stage IV. This patient underwent distal gastrectomy with D2 lymph node resection,
      partial hepatectomy of the S3 region including the metastatic liver tumor and
      coagulation of metastatic liver tumors in the S6 and S7 regions. This patient was
      treated by intra-hepatic arterial infusion of 5-FU, CDDP and peroral
      administration of UFT after surgery. This patient has died at 3 years and 7
      months after surgery. The other case was of a 55-year-old male patient diagnosed
      as having type 2 advanced gastric cancer located in the lesser curvature of the
      cardia with liver metastasis. The stage of this case was P0H1N1T3 M0 stage IV.
      This patient underwent total gastrectomy with D2 lymph node dissection, wedge
      resection of the S8 region including the metastatic liver tumor and coagulation
      of a metastatic liver tumor in the S4 region. This patient was treated by
      obstruction of the hepatic artery using coils, peroral administration of UFT,
      lentinan, MMC, and continuous low-dosage 5-FU and CDDP after surgery. This
      patient has died at 3 years and 6 months after surgery. These results suggest
      that for long-term survival in cases of gastric cancer with liver metastasis,
      hepatectomy or coagulation of the metastatic tumor with postoperative
      chemotherapy are indicated in cases that have no non-curative factors and only a
      few metastatic tumors.

PMID- 11830937
TI  - Cloning and nucleotide sequence of a linear DNA plasmid from Xanthophyllomyces
      dendrorhous (Phaffia rhodozyma).
AB  - Extrachromosomal elements were found in a strain of X. dendrorhous, and were
      characterized as linear DNA forming two well defined groups, pPh1 with 3 high
      copy-number molecules, pPh11 (6.9 kb), pPh12 (5.7), pPh13 (4.7), and pPh2 with 2
      low-copy-number molecules, pPh21 (3.6 kb), pPh22 (3.0). A 4077 bp fragment from
      pPh13 was cloned in pUC18 (pDK1) and sequenced (accession no. AJ 278,424). Seven
      putative ORF and some possible regulator sequences were defined.

PMID- 11830936
TI  - Renal ischemia--reperfusion injury: an inescapable event affecting kidney
      transplantation outcome.
AB  - Ischemia--reperfusion (I-R) injury has been shown to be a common cause of late
      and irreversible complications during a variety of standard medical and surgical
      procedures. The pathogenesis of events which follow the I-R involves both injured
      endothelium and activated leukocytes and their interaction. In kidney
      transplantation, an I-R injury occurs in situations such as graft harvesting,
      cold storage and surgery. Clinical consequences of I-R injury have been
      considered to be delayed graft function and acute rejection in the short term and
      chronic rejection late after transplantation. Here we focused on current
      knowledge of pathophysiology of renal I-R injury in kidney transplantation and on
      possibilities of experimental therapy.

PMID- 11830938
TI  - Plasmids of Selenomonas ruminantium and development of host-vector system.
AB  - A high frequency of plasmids was detected in the rumen bacterium Selenomonas
      ruminantium. Plasmids 0.9-20 kb in size were detected in more than 50% tested
      strains. Densitometric analysis indicated that plasmid DNA could represents more
      than 25% of total cellular DNA. Up to six plasmids were detected in strain S.
      ruminantium 18. Two smallest cryptic plasmids pSRD181 and pSRD182 from this
      strain were cloned into Escherichia coli vector pBluescriptSK+ and partially
      characterized. The plasmid pSRD181 is 1.4 kb and pSRD182 is 2.0 kb. While
      computer analysis of pSRD181 sequence data showed high homology with replication
      protein of Staphylococcus aureus plasmids, the pSRD182 sequence showed no
      significant homology in GenBank data. Strain S. ruminantium 28 was successfully
      transformed with pJW1 derived plasmid pJ1B1 using ampicillin resistance gene as
      marker. This is the first report on transformation of selenomonads with foreign
      DNA.

PMID- 11830939
TI  - Use of yeast two-hybrid system for detection of Bacillus subtilis FtsZ protein
      partners.
AB  - Yeast two-hybrid system was modified to allow easy detection of prokaryotic
      protein-protein interactions. Three plasmids (pGBR1, pGBR2, pGBR3) with the ClaI
      restriction site shifted in the three possible reading frames in fusion with GAL4
      activating domain were constructed. The modified plasmids were used for
      identification of protein partners of FtsZ from Bacillus subtilis. Among partners
      of FtsZ the FtsA protein and a globular part of the SpoIIE protein were
      identified. The protein interactions were quantified by measurements of beta
      galactosidase activity in yeast cells using 4-methylumbelliferyl beta-D
      galactopyranoside as fluorogenic substrate.

PMID- 11830940
TI  - Growth of moderately halophilic bacteria isolated from sea water using phenol as
      the sole carbon source.
AB  - Moderately halophilic bacteria utilizing phenol as the sole carbon source were
      isolated by selective enrichment from sea water. The isolate (Gram-negative
      motile rods) was identified as Deleya venusta. It grew well in the presence of up
      to 1600 mg/L of phenol and 8% NaCl under aerobic conditions. When the cells were
      treated with chloramphenicol prior to the addition of phenol they did not utilize
      added phenol, even after prolonged incubation. Thus, the enzymes necessary for
      phenol metabolism appeared to be inducible.

PMID- 11830941
TI  - Production, characterization and properties of polysaccharide depolymerizing
      enzymes from a strain of Curvularia inaequalis.
AB  - Xylanase, beta-glucosidase, beta-xylosidase, endoglucanase and polygalacturonase
      production from Curvularia inaequalis was carried out by means of solid-state and
      submerged fermentation using different carbon sources. beta-Glucosidase, beta
      xylosidase, polygalacturonase and xylanase produced by the microorganisms were
      characterized. beta-Glucosidase presented optimum activity at pH 5.5 whereas
      xylanase, polygalacturonase and beta-xylosidase activities were optimal at pH
      5.0. Maximal activity of beta-glucosidase was determined at 60 degrees C, beta
      xylosidase at 70 degrees C, and polygalacturonase and xylanase at 55 degrees C.
      These enzymes were stable at acidic to neutral pH and at 40-45 degrees C. The
      crude enzyme solution was studied for the hydrolysis of agricultural residues.

PMID- 11830942
TI  - Streptomyces plicatus as a model biocontrol agent.
AB  - Three hundred and seventy two isolates belonging to the genus Streptomyces were
      isolated and screened for chitinase production. Streptomyces plicatus was found
      to be the best producer. The highest chitinase production were incubated for 3 d
      at 30 degrees C on buffered culture medium (pH 8.0) containing chitin plus
      sucrose and calcium nitrate as carbon and nitrogen sources. S. plicatus chitinase
      had a highly significant inhibitory effect on spore germination, germ tube
      elongation and radial growth of Fusarium oxysporum f.sp. lycopersici, Altrernaria
      alternata and Verticillium albo-atrum, the causal organisms of Fusarium wilt,
      stem canker and Verticillium wilt diseases of tomato. Application of S. plicatus
      to the root system of tomato plants before transplantation markedly protected
      tomato plants against the tested phytopathogenic fungi in vivo.

PMID- 11830943
TI  - Poly-3-hydroxybutyrate production by Azotobacter chroococcum.
AB  - Thirty-seven soil isolates and mutants of Azotobacter chroococcum tested for poly
      3-hydroxybutyrate (PHB) production using Sudan black B staining method were found
      to be positive. One mutant showed a higher number of PHB-producing cells and
      maximum number of granules per cell. Using 2% glucose and 15 mmol/L ammonium
      acetate, PHB production was found to be maximum at 36 and 48 h of growth under
      submerged cultivation and under stationary cultivation, respectively. PHB
      production was found to be higher on sucrose and commercial sugar (as carbon
      sources) as compared to glucose and mannitol. As commercial sugar is cheaper than
      sucrose it was selected as carbon source for PHB production, that being found to
      be maximum at 1% concentration. Inorganic nitrogen sources seemed to have no
      stimulatory effect on the production of PHB. However, ammonium acetate (15
      mmol/L) was found to be best for PHB production. Peptone (0.2%) gave a better
      yield of PHB under both growth conditions. Using all optimized conditions, PHB
      production was studied in ten selected strains. Two of them were found to be best
      PHB producers under both growth conditions, one producing 621 and 740
      micrograms/g dry mass under submerged cultivation and under stationary
      cultivation, respectively, while the second one produced 589 and 733
      micrograms/g.

PMID- 11830944
TI  - Virulence factors of clinical isolates of Aeromonas caviae.
AB  - The mechanism of pathogenicity of 13 Aeromonas caviae strains isolated from fecal
      specimens of children with diarrhea was examined. Isolates possessed several
      virulence agents. Six of 13 isolates produced cholera-like toxin, all strains
      exhibited adhesive ability and secreted catecholate siderophores. Six isolates
      were able to grow in heat-inactivated serum. Production of hemolysins was not
      detected. The isolates had relatively high values of LD50 in a mouse model, which
      suggests that there is no linkage between pathogenicity to mice and the
      diarrheagenic ability of the isolates.

PMID- 11830945
TI  - Selection and evaluation of Azospirillum brasilense strains growing at a sub
      optimum temperature in rhizocoenosis with wheat.
AB  - Fourteen Azospirillum brasilense strains growing at a sub-optimum temperature
      were selected based on their ability to grow and carry out plant growth promoting
      activities at 22 degrees C. The strains were tested for their response to
      inoculation in wheat (two popular cultivars, HD2285 and WH547, under sterile
      conditions) crop using sterile and nonsterile rooting medium. Significant
      increase in plant growth parameters was observed; the overall response to
      inoculation was better in cultivar HD2285. Based on their performance under
      sterile conditions, 4 strains were selected and compared under nonsterile
      conditions with strain sensitive to a sub-optimum temperature in pots using wheat
      variety HD2285. The strains capable of growing at the sub-optimum temperature can
      colonize the wheat endorhizosphere efficiently and improve the plant growth and
      yield as compared to sensitive strain; a 25-27% increase in grain yield was found
      on inoculating two selected strains compared to NO3- control.

PMID- 11830946
TI  - Incidence of Candida species isolated from human skin and nails: a survey.
AB  - Distribution of Candida species was investigated by examining 245 samples from
      skin lesions and nails. The isolates were identified using standard laboratory
      methods including germ tube test, micromorphology of colonies on rice agar, the
      commercial kit, saccharide assimilation and fermentation tests. Eight species of
      Candida were identified: C. albicans accounted for 56.4% of the isolates, C.
      parapsilosis 29.1, C. tropicalis 7.8, C. pulcherrima 2.9, C. guilliermondii 1.5,
      C. krusei and C. zeylanoides for 0.9% each, and C. robusta for 0.5%. The factors
      significantly associated with colonization were prolonged antibiotic therapy,
      parenteral nutrition, low birth body mass of infants, intubation, duration of
      stay in hospital, indwelling intravenous catheter, malignancies, diabetes,
      surgery, and obesity.

PMID- 11830947
TI  - Occurrence and transferability of beta-lactam resistance in Enterobacteriaceae
      isolated in Children's University Hospital in Bratislava.
AB  - Occurrence and transferability of beta-lactam resistance in 30 multi-resistant
      Escherichia coli, Klebsiella spp., Enterobacter spp., Pantoea agglomerans,
      Citrobacter freundii and Serratia marcescens strains isolated from children
      between 0 and 3 years of age is presented. The strains were resistant to
      ampicillin (30), cefoxitin (22), cefotaxime (30), ceftriaxone (30), ceftazidime
      (30) and aztreonam (28), but susceptible to cefepime (30) and imipenem (26).
      Twenty-eight of 30 isolates possessed a transferable resistance confirmed by
      conjugation and isolation of 79-89-kb plasmids. The beta-lactam resistance was
      due to production of beta-lactamases and ceftazidime proved to be stronger beta
      lactamase inductor than ceftriaxone. Twenty-five clinical isolates expressed
      transferable extended spectrum beta-lactamases, and chromosomally encoded AmpC
      beta-lactamase.

PMID- 11830949
TI  - Nitric oxide metabolites in gnotobiotic piglets orally infected with Salmonella
      enterica serovar typhimurium.
AB  - Reactive NO metabolites play a distinct role in the control of Salmonella
      enterica serovar Typhimurium (ST; a facultative intracellular pathogen) in
      susceptible host. A significant increase of nitrite and/or nitrate plasma levels,
      3-nitro-tyrosine expression and pathological changes in mesenteric lymph nodes
      have been observed in gnotobiotic piglets orally infected for 1 d with a virulent
      strain of ST but not in piglets infected with a rough mutant of ST.

PMID- 11830950
TI  - Cutaneous candidosis in immunosuppressed patients.
AB  - One-hundred patients with candidosis of the skin, mucous membranes and nail
      plates (confirmed by cultivation) were examined. Topical or systemic antimycotic
      treatment was successful in 58 patients. After a complete evaluation, 42 patients
      were found to suffer from factors supporting candidosis--diabetes mellitus (12),
      anemia (3) and various local factors (10 patients); 27 patients showed a
      deficiency in cell-mediated immunity. In addition to intensive antimycotic
      therapy, successful treatment is affected by the actual immunity level and can be
      ensured by efficient immunomodulation treatment of immunodeficiency.

PMID- 11830948
TI  - Cytokines and other important inflammatory mediators in gestation and bacterial
      intraamniotic infections.
AB  - Intraamniotic infections caused by viruses, bacteria or mycoplasmas are
      frequently followed by damage of fetus or increased perinatal morbidity and
      mortality. Cytokines are key substances regulating a number of biological
      processes including reproductive and inflammatory processes. An association
      between intraamniotic infections, rising concentrations of inflammatory cytokines
      in amniotic fluid and preterm labor is suggested. A great effort is made to find
      reliable markers typical for intraamniotic infections with high predictive value
      that make possible prompt identification of patients with intraamniotic
      infection. This review concerns inflammatory mediators, especially IL-1, IL-6, IL
      8, TNF-alpha, and other important biologically active substances as
      prostaglandins and NO metabolites and their roles in intraamniotic infections.
      Finally, we discuss their relevance for diagnosis of intraamniotic infections.

PMID- 11830951
TI  - [Treatment with soft laser. The effect on complaints after the removal of wisdom
      teeth in the mandible].
AB  - In a placebo controlled double-blind randomized study the effect of low level
      laser therapy on postoperative complaints after removal of lower third molars was
      examined. Several parameters were investigated in two groups of patients; in one
      group low level laser was applied during and following third molar removal, in
      the other no active additional laser treatment was given. The results of this
      study show that therapeutic low level laser treatment could not statistically
      reduce the postoperative pain, swelling, trismus and function impairment after
      extraction of lower third molars.

PMID- 11830952
TI  - [Tooth development in children with cleft lip and palate. An international
      inquiry into unilateral cleft lip, jaw and palate].
AB  - In a cross-sectional study of 106 European children with unilateral complete
      cleft lip, alveolus and palate ranging from 10 to 15 years of age, dental
      maturity was determined using orthopantomograms. The method and standards (the
      50th percentile line) of Demirjian were used. The study shows a significant delay
      of dental maturity in both male and female cleft-affected patients. This delay in
      tooth development supports Van Limborgh's theory that the origin of clefts is due
      to the delayed growth and development of parts of the dentofacial area.

PMID- 11830953
TI  - [Dental care for elderly people. Inventory and recommendations].
AB  - This article presents a brief review of the existing literature on dental care
      for elderly people. Also, based on this review and its conclusions, some
      guidelines are given in order to improve the dental care for elderly people.

PMID- 11830954
TI  - [Multiple jaw cysts].

PMID- 11830955
TI  - [HIV and dentistry. Part 3. HIV infection: pathogenesis, epidemiology,
      definitions and classification].
AB  - The acquired immunodeficiency syndrome (AIDS) is caused by a retrovirus, the
      human immunodeficiency virus (HIV), that selectively deteriorates cell-mediated
      immunity. Consequently fatal opportunistic infections and/or malignancies occur.
      In this paper the pathogenesis and the epidemiology of HIV infection are
      described. In addition the 1993 revised classification for HIV infection and the
      expanded surveillance case definition for AIDS are presented.

PMID- 11830956
TI  - [Midazolam sedation in the general dental practice].
AB  - The general dental practitioner is occasionally confronted with patients who, on
      the basis of psychological--and often somatic--criteria, are difficult to treat.
      Medicinal sedation in combination with anxiety reduction may be deemed
      appropriate for such patients. In the Netherlands inhalation sedation by means of
      a combination of oxygen and nitrous oxide is generally used. The limitations and
      disadvantages of this method have directed attention towards sedation by means of
      midazolam, a quick-acting benzodiazepine. In view of the complications which may
      accompany the administration of midazolam, the general practitioner working alone
      or in a group practice is advised against using midazolam sedation. Such use
      should be reserved for a dentist working in a hospital setting, who is able to
      consult with a physician regarding the advisability of administering midazolam.
      Even then, the safety of the patient requires that the practitioners have a
      proper insight into the physical state of the patient, work according to a
      protocol and in accordance with clearly defined responsibilities, and provide
      adequate accommodation during and after treatment.

PMID- 11830957
TI  - [Amalgam. XIII. Criticism on dental amalgam: right or wrong?].
AB  - Some brief remarks, partly based on Dutch legislation, are made on the dentists'
      attitude towards the use of dental amalgam. The patient is entitled to ask for
      dental restorative materials other than amalgam. On the other hand, the dentist
      is entitled to refuse to apply materials that are, according to the prevailing
      professional standards, inappropriate in a given situation.

PMID- 11830958
TI  - [Chemoprevention of (pre)malignant disorders of the head and neck area. Current
      situation].
AB  - A brief review is presented of various ongoing chemoprevention studies on head
      and neck cancer. Although beta carotene and several retinoids seem to be
      effective, scientific proof is at yet insufficient. The need of biomarkers as
      intermediate end-points is stressed.

PMID- 11830959
TI  - [The appearance after osteotomy of the jaw].
AB  - A patient undergoing orthognathic surgery wants to know in advance what he will
      look like after the treatment. For this purpose a prediction tracing may be used.
      The value i.e. precision of such a tracing is discussed. Several factors seem to
      limit the reliability of the prediction, such as 1. the surgery is not always
      executed as planned; 2. a (partial) relapse influences the final result; 3.
      rotational movements cannot yet be integrated with precision in the prognosis; 4.
      the ratios used in the planning are not absolutely reliable. Nevertheless, the
      prediction tracing is useful if one is aware of its shortcomings.

PMID- 11830960
TI  - [Implants in combination with an overdenture. Indications for the number of
      implants needed].
AB  - Considerations regarding the choice of the number of implants to be placed in
      combination with an implant-retained overdenture are discussed. Primarily, the
      characteristics of the chosen retention mechanism should be considered, as well
      as the magnitude and direction of forces on the implant-bone interface delivered
      through the suprastructure and implant, and the expected effects on the
      antagonist denture and/or jaw.

PMID- 11830961
TI  - [Amalgam. XIV. Oral galvanism].
AB  - Although 'oral galvanism' is associated with corrosion, it seems to be an
      irrelevant phenomenon. It is very difficult to measure correctly electric
      currents in the mouth, if possible at all, and the value and significance of the
      results are questionable. Occasionally a patient may perceive an electric
      current, i.e. pain or taste sensation, due to intermittent contacts between
      restorations of amalgam and gold. A damaging effect, however, has never been
      proven.

PMID- 11830962
TI  - [HIV and dentistry. Part 4. Oral deviations in HIV infections: present
      classification and diagnostic criteria].
AB  - In the present classification of oral lesions associated with HIV infection a
      distinction is made between presumptive and definitive diagnostic criteria. The
      former relate to the initial clinical appearance of the lesion and the latter are
      often the result of special investigations. Candidiasis, hairy leukoplakia,
      specific forms of periodontal disease, Kaposi's sarcoma and non-Hodgkin's
      lymphoma are strongly associated with HIV infection. Lesions less commonly
      associated with HIV infection and lesions seen in HIV infection, but not
      indicative of the disease, are also listed.

PMID- 11830963
TI  - [Anxiety disorders in the dental practice. Part 1. Recognition of anxious
      patients].
AB  - The purpose of the present paper is to provide a summary of features of patients
      suffering from a wide range of anxiety disorders by means of case histories and
      clinical descriptions. Particularly, attention is being devoted to distinguishing
      between patients of which the predominant problem is specific fear for one or
      more aspects of dental treatment and patients with a non-specific or a general
      anxiety problem, including panic disorder and generalized anxiety disorder.

PMID- 11830964
TI  - [Dental care under general anesthesia. An inquiry among dentists in the
      Netherlands].
AB  - In 1991 an inquiry among dentists (n = 49, response 86%) who treat patients under
      general anaesthesia, revealed the restricted capacity for this treatment
      possibility in the Netherlands. The continuity of this type of dental care seems
      to be at stake by an insufficient structure and for lack of education in this
      field.

PMID- 11830965
TI  - [Retention of adhesive bridges].
AB  - Since the development of adhesive bridges in the early seventies, the retention
      and therefore the durability of these bridges has been tremendously improved.
      Conditioning of the non-precious metal by silanisation, careful acid etching of
      the enamel and the use of the appropriate composite resin are of prime
      importance. Furthermore, the meticulous preparation with enough interproximal
      embrace, occlusal rests, interocclusal clearance and cingulum stops is equally
      important. Including more teeth in the design does not necessarily lead to an
      improved retention. Besides the material and technical aspects, the whole
      clinical procedure needs much attention. The retention does not depend on one
      single factor, but on the precision of all the necessary clinical steps and on a
      well-defined selection of the material. In this way a five-year survival rate of
      close to 80% can be obtained.

PMID- 11830966
TI  - [Multiple idiopathic apical root resorption].

PMID- 11830967
TI  - [Oral hygiene: effective and safe].
AB  - Daily oral hygiene is a matter-of-course. However, many people disregard the
      difficulties of effective cleansing of the dentition and need to be made aware of
      the problems; in everyday practice, more attention must be given to detailed
      individual instruction and recall. A systematic order of cleansing, the use of
      the proper instruments in the proper way and particularly the avoidance of
      traumatic forces are important to prevent damaging side effects, such as gingival
      recession, abrasion and erosion. Patients with periodontal problems are in need
      of conscientious instruction after their initial treatment, as careful plaque
      control has proven to be effective in the prevention of further deterioration.
      Moreover, patients with an increased risk of plaque retention, due to
      restorative, prosthetic and orthodontic devices or implants, need special care
      and frequently repeated instructions.

PMID- 11830968
TI  - [Oral hygiene aids].
AB  - Different dental hygiene aids are discussed, such as floss, tape, superfloss,
      gauze, flat shoelace, toothpick, interproximal brush, single-tufted brush,
      electric toothbrush, manual toothbrush and oral irrigation. Research shows that
      not one specific aid is superior to another if effectiveness is taken into
      consideration. Other factors which can influence oral hygiene efficacy are
      discussed as well.

PMID- 11830969
TI  - [The electric toothbrush. Present situation].
AB  - During the last decade several electric toothbrushes have been introduced with an
      innovative brushing technique. Scientific research indicates that after proper
      oral hygiene instruction these toothbrushes can be more effective than a manual
      toothbrush. This increased efficacy is mainly caused by an improved plaque
      removal from the proximal surfaces. Besides effectiveness, reasons such as
      facility and boosting of motivation can be reasons to advise the use of an
      electric toothbrush. However, these secondary arguments have sofar not been
      supported by scientific data.

PMID- 11830970
TI  - [Chemical plaque inhibitors. Their use in mouthwashes and toothpastes].
AB  - Despite the fact that many mouthrinses are available and much research is being
      devoted to better and new mouthwashes, as yet there is no form of chemical plaque
      control that can totally replace mechanical plaque removal. However, at this
      moment there is a promising compound. Triclosan, in combination with a copolymer,
      has already been added to a toothpaste and mouthrinse.

PMID- 11830971
TI  - [Prevention of dental caries with chlorhexidine].
AB  - The presence of > or = 10(6) mutans streptococci per ml saliva may indicate a
      high caries risk or activity. Individuals exhibiting these high levels of mutans
      streptococci are ironically called 'millionaires'. It has been demonstrated that
      the reduction of the mutans streptococci with a series of chlorhexidine gel
      treatments, reduces the caries incidence in millionaire children. Recently, two
      chlorhexidine varnishes have been shown to reduce the mutans streptococci in
      plaque and saliva significantly. It may be expected that the application of these
      chlorhexidine varnishes may reduce caries incidence in 'millionaires'. It may
      also be possible to treat individual sites of the teeth that are at risk.

PMID- 11830972
TI  - [Nutrition education and oral health].
AB  - At present, reduction of the consumption of fat is the main issue in nutritional
      education. However, this can lead to an increased consumption of mono- and
      disaccharides and, as a result, to increased dental caries. Individual variations
      in the susceptibility of caries make it necessary to differentiate the advice for
      the consumption of snacks between meals. Generally, consumption of complex
      carbohydrates, such as bread or bread products, can be advised as an alternative
      for fat and sugar containing snacks. Sugar-free products can also be advised, but
      not unlimited because of the laxative effect of sorbitol. To prevent tooth
      erosion the frequent consumption of fruits and fruit juices should be
      discouraged.

PMID- 11830973
TI  - [Patient education and therapy compliance].
AB  - The effects of oral health promotion activities depend on the degree of patient
      compliance, the extent to which a patient's behaviour is in accordance with
      dental health advice and instructions. Compliance is considered as a complex
      phenomenon. With the help of theories and models of health behaviour and the
      results of advertising research and consumer behaviour studies, some views are
      presented to increase patient compliance in dental practice.

PMID- 11830974
TI  - [Preventive orthodontics].
AB  - In this article orthodontic preventive and interceptive measures are discussed.
      The number of environmental factors that can be influenced to prevent
      malocclusions is rather small.

PMID- 11830975
TI  - [Preventive periodontal care. Experience from general practice].
AB  - In a general dental practice treatment of all patients (N = 740) in the age of 15
      65 years was directed towards reduction of sulcus (pocket) depths by scaling,
      planing and surgical corrections, and towards maintenance of the reduced pocket
      pattern. Before this treatment, one third of the patients (35 years and older)
      had light to severe forms of adult peridontitis. It was shown that the reduced
      pocketpatterns could be maintained in all age groups (20-35, 36-50, 51-77).
      Individual treatment-time for sub- and supragingival cleaning with scalers and
      curettes varied from 10 to 60 minutes per patient per year. Already during
      adolescence subgingival cleaning should be a standard procedure two times a year
      in order to prevent periodontitis and should be directed in the first place
      towards the approximal surfaces of the molars.

PMID- 11830976
TI  - [Preventive prosthetics and gnathology].
AB  - In daily practice the dentist is constantly confronted with dentitions which do
      not measure up to the (idealized) parameters of a theoretically ideal occlusion.
      In many cases there is a healthy situation which should be maintained. Changes to
      the occlusion and/or prosthetic treatment should only take place if they are
      predicted, beforehand to contribute to solving relevant problems. Clinical
      application of preventive measures in relation to the function of the masticatory
      system as well as prosthetic treatment are discussed.

PMID- 11830977
TI  - [Prevention of oral cancer].
AB  - Etiology control is the most important primary prevention of oral cancer. The use
      of tobacco and alcohol increases the risk of a squamous cell carcinoma of the
      oral mucosa. The dentist can play an important role in the secondary prevention
      or screening for premalignant lesions, asymptomatic malignancies and second
      primary tumours of the oral cavity. Because of their age, edentulous patients run
      a high risk of oral cancer. Therefore, a regular oral check-up of these patients
      should be recommended.

PMID- 11830978
TI  - [Preventive oral and dental care in radiotherapy patients].
AB  - An overview is presented of the preventive measures that can be taken with regard
      to the various side effects of radiotherapy of the head-and-neck region.
      Xerostomia, mucositis, radiation caries, trismus and osteoradionecrosis are to
      some extent preventable.

PMID- 11830979
TI  - [HIV and dentistry. Part 5. Practice hygiene].
AB  - When complying a good standard hygiene protocol in the dental office the risk of
      cross-infection of whatever type of microorganism, including the hepatitis-B
      virus and HIV, is almost eliminated.

PMID- 11830980
TI  - [Efficient preventive dentistry. Concluding article].
AB  - In this concluding article by the Dutch Advisory Council on Prevention of Oral
      Diseases, the relative importance of various aspects of prevention is sorted out.
      A guideline is presented to dentists, dental hygienists and oral health
      educators, regarding the contents of an efficient and comprehensive package of
      basic preventive measures. Subsequently, supplementary measures of prevention are
      discussed, which should be considered for certain age categories and high-risk
      groups. Top priority is attributed to regular mechanical cleansing of the
      dentition, combined with daily administering of fluoride.

PMID- 11830981
TI  - [Halitosis (fetor ex ore). A review].
AB  - About 15% of the Dutch population has, in a more or lesser degree, complaints
      about bad breath. This is caused particularly by the anaerobic metabolism of a
      number of oral microorganisms, in which putrefaction occurs and volatile sulfur
      compounds will be formed. Some of these compounds are also possibly involved in
      the pathogenesis of periodontitis. A good oral hygiene is of primary importance
      to prevent halitosis and to reduce bad breath. Antiseptic mouth-waters can be
      helpful in the reduction of the bacterial metabolism. In addition, stimulation of
      the salivary secretion has a dual favourable effect, firstly because of its
      antimicrobial salivary proteins, and secondly by reduction of the retention of
      nutrients in the oral cavity.

PMID- 11830982
TI  - [Anxiety and depression in craniomandibular disorders; the use of the Symptom
      Checklist 90].
AB  - Anxiety and depression of CMD-patients in a Clinic for Special Dental Care were
      assessed with the Symptom Checklist-90. The results of the female patients did
      not differ from the general population; the men showed significantly higher
      scores. Approximately one third of the patients scored 'high' or 'very high' on
      anxiety or depression and may need special attention for psychological problems.
      The SCL-90 may be a useful instrument to assess the presence of clinically
      significant anxiety or depression. Psychological data should be interpreted with
      great care and always in combination with data from the dental examination.

PMID- 11830984
TI  - [Prevention of medical emergencies].

PMID- 11830983
TI  - [Patient care and ethics. VIII. Ethics education in dental education in the
      United States].
AB  - Dental ethics with its specific aspects has obtained a distinct profile during
      the past ten years. This article presents a recent impression of courses in
      dental ethics at a number of dental schools in the USA. Some reflections are
      given about the continuing development of dental ethics.

PMID- 11830985
TI  - [How many prostheses do we need? Changing goals in dental restorations in risk
      groups].

PMID- 11830986
TI  - [A blood blister on the roof of the mouth].

PMID- 11830987
TI  - [HIV and dentistry. Part 1: Disclosure of HIV-seropositivity to the dentist].
AB  - For a number of reasons it is recommended to disclose one's HIV-seropositivity to
      the dentist. This information will enable the dentist to take extra precautions
      during treatment. Furthermore, extra measures may be taken with regard to
      prevention or early treatment of dental and oral diseases, e.g. gingivitis,
      candidiasis. The dentist and the other members of the dental team are supposed to
      obey strict confidentiality.

PMID- 11830988
TI  - [Amalgam. XI. Glass-ionomer as a possible substitute of amalgam: longevity].
AB  - The clinical use of glass-ionomer increases, also for restorative goals. The
      longevity of glass ionomer restorations is among others determined by premature
      contact with saliva and by acid erosion. The adherence to the dental hard tissues
      may be increased by acid pretreatment. The longevity data presented here indicate
      that glass ionomer restorations do not last as long as amalgam restorations. In
      the deciduous teeth the material seems to be a more acceptable substitute for
      amalgam. The same holds true for restorations which are not submitted to stress,
      such as class V.

PMID- 11830989
TI  - [An evaluation of completely ceramic crowns].
AB  - All-ceramic crowns (Cerestore by Johnson & Johnson) were made on premolars and
      molars following two procedures: the finishing line was a straight shoulder or a
      hollow chamber. In vivo replicas were made of the marginal zone on the buccal and
      on the lingual side. The replicas were studied with scanning electron microscopy.
      Results showed a relatively large variability in marginal discrepancy in the same
      crown margin ranging from 12.2 mm to 134.3 mm. In a second series of crowns even
      discrepancies up to 232.7 mm have been measured. The discrepancy slightly
      increased after cementation. Several crowns fractured during the try-on session.
      No crowns fractured after cementation in a six months' interval. The gingiva
      surrounding the crowns remained healthy. The esthetic results were sometimes poor
      due to the whitish core not covered by porcelain. This study suggests that the
      Cerestore crowns are acceptable as a solitary restoration in premolar and molar
      region but that both esthetics and marginal fit can be improved.

PMID- 11830990
TI  - [HIV and dentistry. Part 2. Needlestick injury].
AB  - The risk for dentists to acquire HIV infection at work is low but not
      neglectable. Needlestick injuries are among the most hazardous events in this
      respect. Prevention of these injuries will considerably reduce the risk of
      occupational HIV infection in dentistry.

PMID- 11830991
TI  - [Amalgam. XII. Amalgam removed and patient cured?].
AB  - The aim of this article is to present a critical reflection on 'cures of
      patients' after the removal of dental amalgam fillings, reported in the popular
      press. It is concluded that, when the removal of dental amalgams in patients with
      a hypersensitivity to mercury is put aside, possible explanations for these
      questionable cures are not connected with the removal of amalgam but may involve
      the functioning of the immune system, the relation between environment and the
      opinions of patients and the influence of psychological factors on illness and
      health.

PMID- 11830992
TI  - [Results of youth dentistry. Oral health and oral hygiene habits of children
      participating in regional institutions].
AB  - In order to evaluate the results of Regional Institutions (RI's) for Youth
      Dentistry, an epidemiological study was performed on caries experience and oral
      hygiene habits of 5-, 8- and 11-year-olds, getting dental treatment in these
      institutions. In the big cities participants of the RI's appeared to be mostly
      from the lower social levels of society and ethnic minority groups. Caries
      experience and oral hygiene habits of these children were relatively
      unfavourable. A significant statistical correlation exists between oral hygiene
      habits and caries experience. Differences between the results of the RI's with
      respect to the oral health and the oral hygiene habits of the participants can be
      explained to a large extent by the mentioned social and ethnic differences.

PMID- 11830993
TI  - [Open mouth posture. A review].
AB  - Open mouth posture is a risk factor for otitis media with effusion, orthodontic
      anomalies and possible other medical disturbances. In this article the relation
      between open mouth posture and orthodontic anomalies is discussed. The importance
      of early diagnosis, prevention and (interceptive) treatment is emphasized.

PMID- 11830994
TI  - [A red spot in the mouth floor].

PMID- 11830995
TI  - [Pathophysiology and treatment of severe intractable asthma].

PMID- 11830996
TI  - [Effect of endothelin on DNA synthesis in human bronchial epithelium: role of MAP
      kinase cascade].
AB  - To elucidate the effect of endothelin (ET) on airway epithelial cell
      proliferation, we measured intracellular DNA levels and assessed a possible
      contribution of mitogen activated protein kinase (MAPK) cascade to the ET action.
      Incubation of transformed human bronchial epithelial (16 HBE) cells with ET in
      the serum-free medium caused time-dependent increases in DNA synthesis and MTT
      reduction, an effect that was attenuated by the MAPK kinase inhibitor PD 98059 in
      a concentration-dependent manner. Western blot analysis showed that ET induced
      the expression of phosphorylated MAPK protein, indicating an activation of MAPK,
      and that this effect was inhibited in the presence of PD 98059 or the ETA
      receptor antagonist BQ-123. These results suggest that ET may stimulate the
      proliferation of human airway epithelium via ETA receptors and the concomitant
      activation of MAPK cascade.

PMID- 11830997
TI  - [Comparison between real-time pollen monitor KH-3000 and Burkard sampler].
AB  - Special apparatus capable of instantly measuring airborne Cryptomeria japonica
      pollen grains were recently appeared on the market. We examined one of them
      called real-time pollen monitor KH-3000 (Yamato Manufacturing Co. Ltd.). To
      confirm the accuracy of the monitor, comparison was made with conventional
      Burkard Seven-Day Recording Volumetric Spore Trap operating simultaneously at the
      same place. Most peaks from KH-3000 were coincided with Cry j 1 from Burkard
      sampler, and the greater part of the counts from KH-3000 had a strong resemblance
      to the counts from Cry j 1. Therefore, it is confirmed that KH-3000 counts the
      numbers of airborne C. japonica pollen grains. KH-3000 sometimes counts particles
      which do not belong to pollen grains, however. It is also confirmed that some
      pollens other than C. japonica, such as walnut (Juglans spp.) pollen, a part of
      grass pollen were counted.

PMID- 11830998
TI  - [Changes in the prevalence of asthma-like symptoms and risk factors in school
      children in Yokohama from 1986 to 1991].
AB  - We conducted a questionnaire survey of first graders from six elementary schools
      in three areas of Yokohama annually from 1986 to 1991 (about 700 children each
      year) to investigate the changes in prevalence of asthma-like symptoms and
      association with potential risk factors. The prevalence rate of asthma-like
      symptoms increased from 7.6% to 11.0% in boys and from 6.5% to 8.8% in girls from
      1986 to 1991. The ratio of affected boys was consistently higher than that in
      girls, but there were no significant regional differences. We found statistically
      significant odds ratios for the effect of a previous history of allergies,
      respiratory disease before age two, wheezing or difficulty in breath before age
      two and cough without respiratory tract infections on the prevalence of asthma
      like symptoms.

PMID- 11830999
TI  - [Induction of atopic dermatitis-like skin lesion in NC/Nga mice--the influence of
      the skin barrier destroying solution to the induction of dermatitis].
AB  - NC/Nga mouse is well known as a mouse model for atopic dermatitis. In general,
      when NC/Nga mouse are raised under specific pathogen free (SPF) conditions no
      skin lesions are detected, but when under non-filtrated (conventional) condition,
      atopic dermatitis like skin lesions appear spontaneously. However, this
      dermatitis develops in 70-90% of mice (not 100%), which makes it difficult to
      perform reproducible experiments every time. This study was performed under SPF
      conditions, using the four solutions (2% SDS, 4% SDS, ethanol, acetone/ether) to
      destroy the skin barrier function, and thereafter, applying the extracted
      solution of mite: Dermatophagoides pteronyssinus, which is a very popular antigen
      in pathogenesis of human atopic dermatitis. The extracted solution of mite was
      applied repeatedly on the NC/Nga mice with a pretreatment of barrier destroying
      solution and after 8 weeks the mice developed severe dermatitis (clinical skin
      condition score of 7-10.2 points) with marked elevation of plasma IgE level,
      whereas mice coated only with the barrier destroying solution showed weak skin
      lesion with no elevation of plasma IgE level. BALB/c mice, which are employed as
      control, showed weak skin lesion (clinical skin condition score of 0-3.8 points)
      and slight elevation of plasma IgE level after repeated application of the
      extracted solution of mite with a pretreatment of the barrier destroying
      solution, whereas mice coated only with the barrier destroying solution showed
      weak skin lesion and the no elevation of plasma IgE level was observed. In this
      study, using several solutions to disturb the skin barrier function before
      applying the antigen, we have found a suitable condition and types of solutions
      in inducing dermatitis in NC/Nga mice.

PMID- 11831000
TI  - [Prevalence of asthma in adults in Menda town rural-mountain area in Japan].
AB  - Several reports have suggested that the prevalence of asthma in adults is
      currently increasing. However, recent prevalence of asthma has not reported in
      Japan, especially in rural-mountain areas. To investigate the prevalence of
      asthma in adults in Japan, we conducted clinical epidemiological research on 5066
      inhabitants of Menda town, in a rural-mountain area of Japan. The study
      population comprised 98.7% of adults in the town, including senior high school
      students whose age were more than 15 years old. The prevalence of asthma among
      adults was 3.6%. The ratio of prevalence in males to prevalence in females was
      1.44. Peaks prevalences were observed in the age ranges of 15-19 and > 70 years
      old in males, and 15-19, 40-49 and > 70 years old in females.

PMID- 11831001
TI  - [A case of minocycline-induced pneumonitis after percutaneous instillation into
      renal cysts].

PMID- 11831002
TI  - [Alternative therapeutic strategies for intractable ulcerative colitis].

PMID- 11831003
TI  - [Recent advances in treatment of Crohn's disease].

PMID- 11831004
TI  - [The prophylaxis of wound infection in pull-percutaneous endoscopic gastrostomy:
      Correlation with methicillin resistant staphylococcus aureus positive patient in
      the throat].
AB  - In this study, we elucidated the efficacy of our prophylactic method for wound
      infection in pull-percutaneous endoscopic gastrostomy (PEG). The total 29
      patients received the pull-PEG. The first 8 patients received the oral
      sterilization with povidone iodine and antibiotics at the time of pull-PEG (Group
      I). The frequency of wound infection in this group was 50.0% (4/8). It was
      revealed that all infections were induced by methicillin resistant staphylococcus
      aureus (MRSA). 3 patients were MRSA positive in the throat. In Group-II, we
      eradicated MRSA in the throat before the pull-PEG by combination mupirocin
      calcium hydrate with the Group-I treatment. In contrast in Group-I, the frequency
      of wound infection was significantly reduced in Group-II (4.8%: 1/21). The
      results showed that our eradication method was very useful for prevention of the
      wound infection in pull-PEG treatment.

PMID- 11831006
TI  - [Conversion of paraesophageal hiatal hernia to the "upside-down stomach"--a case
      report].

PMID- 11831005
TI  - [Effect of antiulcer agents on the urea breath test--Comparison between
      rebamipide and ecabet sodium].
AB  - In this study, we assessed whether standard doses of antiulcer drugs rebamipide,
      and ecabet sodium influence the accuracy of the urea breath test (UBT). Without
      medication, values of UBT estimated with nondispersive isotope-selective infrared
      spectrometry did not significantly change during follow-up (average 4.4 months).
      Then, we randomized 21 H. pylori-positive patients without serious disease to
      receive either rebamipide or ecabet sodium for 28 days. UBT was performed at
      baseline, on day 14, on day 28, and 2 weeks after cessation of drugs. On day 14,
      the median value of UBT declined significantly (p = 0.0113) compared to baseline
      with ecabet sodium but not with rebamipide. This caused a false-negative result
      of UBT in one of 11 patients who received ecabet sodium. The decline of UBT
      resolved 2 weeks after drug cessation. In addition, we performed a crossover
      study in 11 H. pylori-positive volunteers with these drugs, and ecabet sodium but
      not rebamipide significantly reduced UBT values (p = 0.0058). These findings
      indicate that ecabet sodium adversely influences the accuracy of UBT and that the
      withdrawal of this drug before testing appears to be necessary to avoid false
      negative results.

PMID- 11831007
TI  - [Two cases of hepatocellular carcinoma showing rapid progression after radio
      frequency ablation therapy].

PMID- 11831008
TI  - [A case of Morgagni hernia prolapsed with the stomach, greater omentum and
      transverse colon].

PMID- 11831009
TI  - [A case of multiple pancreatic pseudocysts penetrating into the spleen].

PMID- 11831010
TI  - [A case of young woman with chronic pancreatitis showing diffuse irregular
      narrowing of the main pancreatic duct with autoantibody-negative].

PMID- 11831011
TI  - [A case of single nodular hepatocellular carcinoma with intrabile duct tumor
      growth].

PMID- 11831012
TI  - [Are you rheumatologist?].

PMID- 11831013
TI  - [Cytopenia associated with low dose pulse methotrexate in the treatment of
      rheumatoid arthritis].
AB  - OBJECTIVES: To assess the associated risk factors of methotrexate (MTX)-induced
      cytopenia in rheumatoid arthritis (RA). METHODS: We followed 420 patients started
      on MTX for RA. We evaluated the frequency and clinical significance of patients
      with cytopenia related to MTX therapy. RESULTS: The prevalence of patients
      remaining in the follow-up in the MTX treatment was 21% at 60 months. eighty
      seven patients (21%) continued treatment. The treatment termination in MTX was
      28% for toxicity, 78 (19%) for no effect, 70 (17%) for relapse and 116 (28%) for
      toxicity and 69 (16%) for other reasons. A total of 10 patients with cytopenia
      related to MTX therapy were identified among them. The prevalence of cytopenia,
      including leukopenia (n = 6), thrombocytopenia (n = 3) and pancytopenia (n = 1),
      estimated to be 2.4% in MTX treated RA patients. Patients with cytopenia received
      2.5-8 mg/w over a mean duration of 60.0 months (10-119 months). nine of 10
      patients received NSAIDs with MTX therapy. The presence of renal abnormality (Cr
      > 1.2 mg/d) was in 3 cases, age over 70 years old in 4 patients, body weight
      under 50 kg in 8 patients, mean corpuscular volume (MCV) over 100 fl in 2
      patients. High MCV value (over 94 fl) was in 7 patients, 6 of whom had some
      symptoms including fever (n = 3) and oral mucosa/lip abnormalities (n = 3). Low
      MCV value (under 84 fl) was in 3 patients, who had no symptom but arthralgia and
      no renal abnormality. And they were younger and received MTX in shorter period
      than high MCV group. CONCLUSIONS: In patients with high MCV (over 94 fl), most
      hematological toxicities seen during the course of MTX therapy can be
      predictable. But, some patients may develop unpredictable hematological reaction.
      We need to monitor hematological examination frequently and observe patients
      closely for the appearance of hematological toxicity throughout the presctiption
      period of MTX irrespective of the duration of treatment.

PMID- 11831014
TI  - [Prospective study of pulmonary embolism after total hip or knee arthroplasty].
AB  - We investigated the incidence of pulmonary embolism after total hip or knee
      arthroplasty. Arterial pO2 while the patient was breathing room air was measured
      at pre-operative day and 5 post-operative day using a Blood Gas Analyzer.
      Selection of patients for perfusion/ventilation scan during this study was
      dependent on the results of arterial blood gas determination that was more than
      10 mmHg depression Of arterial pO2 level after surgery. More than depression of
      that was occurred in 11 patients (17.7%). Eight of them (72.7%) detected
      abnormalities (V/Q mismatch) in perfusion/ventilation scan, and we diagnosed them
      PE. More than 70% of PE was detected by only estimating the pre and post
      operative arterial pO2. It was concluded that the estimation of arterial pO2 (pre
      and post-operation) was useful for the detection of PE, and combining estimation
      of arterial pO2 with the clinical feature evaluation method, low-invasive
      diagnosis and rapid treatment should be possible.

PMID- 11831015
TI  - [Case report of systemic lupus erythematosus patient with hemophagocytic
      syndrome, treated with plasma exchange, with specific reference to clinical
      profile and serum cytokine levels].
AB  - A 42-year-old woman was diagnosed as systemic lupus erythematosus (SLE), because
      of the findings of polyarthritis, leukopenia, positive antinuclear antibody, and
      positive anti DNA antibody. She was treated with predonisolone (PSL) at 10 mg per
      day. She was admitted to our hospital on October 2000 because of spiking high
      fever, skin eruption, and lymph node swelling. Since her illness of SLE was
      considered to be worsening, high dose of corticosteroids were given. However,
      high fever persisted and liver dysfunction was developed with increased serum
      ferritin. Her bone marrow smear showed hemophagocytosis. We made a diagnosis of
      hemophagocytic syndrome (HPS) complicated by disseminated intravascular
      coagulation (DIC). HPS was thought to be induced by viral infection, even though
      causative viral infection was not detected. Her general condition worsened with
      persistent high fever and liver dysfunction. Plasma exchange was carried for two
      consecutive days, followed by cyclosporine A and lipo-dexamethasone, which
      improved her fever rapidly. Her general condition gradually improved. Serum
      levels of ferritin, soluble interleukin 2 receptor (sIL 2-R), interferon-gamma
      and interleukin 6 decreased associated with improvements of her clinical
      condition. We thought plasma exchange could be effective to decrease serum levels
      of cytokine, which was suggested to be the pathogenic to HPS. However serum
      levels of IFN-gamma and IL 6 after plasma exchange did not change in this case.
      Further studies are required to confirm the effects of plasma exchange for HPS.

PMID- 11831016
TI  - [Remarks and discussions about statistical analysis].

PMID- 11831017
TI  - [Autoantigen nuclear body and anti-nuclear body antibody].

PMID- 11831018
TI  - [Pathomechanics and treatment of the fingers in rheumatoid arthritis].

PMID- 11831019
TI  - [Human T-lymphotropic virus (HTLV)].

PMID- 11831020
TI  - Recognition of the deleterious effects of smoking among senior high school male
      students.
AB  - The purpose of this study was to evaluate the prevalence of, attitudes towards,
      and knowledge about cigarette smoking among senior high school male students with
      different levels of academic ability. Self-administered anonymous questionnaires
      were distributed to 2014 students in July 2001. The prevalence of current smokers
      was 10.9% overall. The percentage of nonsmokers increased with academic ability
      level in both first and second graders. Students who recognize that cigarette
      smoking is associated with various diseases were more numerous than those
      reported in a nationwide Japan survey. Their recognition regarding the
      deleterious effects of smoking inclined toward diseases of the respiratory
      system. Correct knowledge concerning the detrimental effects of smoking on 10
      selected diseases differed according to academic ability levels. They also
      thought that environmental tobacco smoke exposure was harmful to nonsmokers'
      health (86.6%). Although they fully understood the harmful effects of smoking,
      the percentage of current smokers who wanted to quit smoking (24.7%) was somewhat
      lower than that of those who did not (30.1%). A considerable number of current
      smokers, 95 of 219, had not made up their mind to quit smoking. To reduce the
      numbers of adult smokers, it is important not only to prevent students from
      starting to smoke or to encourage smokers to quit but also to guide undecided
      smokers in how to quit.

PMID- 11831021
TI  - [Relationship between the fecal mutagenicity and metal content, smoking habit and
      dietary intake].
AB  - OBJECTIVE: The study was carried out to collect basic data on exposure of mucous
      cells of the large intestine to mutagens by investigating the genotoxicity of
      fecal samples from the urban population. Simultaneously, relations with food
      intake (food groups and nutritive components), lifestyle factors and fecal metal
      content was investigated. METHODS: A total of 199 self-collected fecal samples
      from middle aged healthy volunteer living in urban areas of Osaka city were
      freeze-dried and ground in a mill. The mutagenicity of aqueous extracts of the
      ground samples was measured by the umu-test. Metal content of the feces was
      analysed by atomic absorption spectrophotometlly. On the day previous to the
      feces collection, the contents of meals were recorded and confirmed by interview
      with a dietitian. Quantification of nutritive components was carried out using
      the 4th edition of the Japan Food Standard Vomposition Table. RESULTS:
      Mutagenicity of feces was higher in males than in females, and in those aged 40
      49 years than 50-69 years in males but not females. Large differences were found
      for content of 8 metals in the feces; concentrations were in the decreasing order
      of calcium, potassium, magnesium, sodium, zinc, iron, manganese and copper, the
      highest being 20.4 mg for calcium and the lowest was 53.5 micrograms for copper.
      Between the metal contents and mutagenicity, values for zinc and iron showed
      positive correlations and for sodium a negative correlation under S9(+)
      conditions. A weak but significant correlation was observed between the numbers
      of cigarettes smoked per day and S9 (+) mutagenicity. However we could not find
      any relation with food groups or nutritive components. CONCLUSION: It is well
      known that human feces contain many mutagens and carcinogens and that these can
      act directly on the mucous membrane of large intestine. Therefore, it is very
      important to estimate exposure levels. From the present data we can conclude that
      relations between mutation-activity of the feces and diet are complex. Their
      elucidation will require a large number of volunteers who have similar living
      conditions to obtain appropriate data.

PMID- 11831022
TI  - [A study of care workers of human resources in health-social services].
AB  - OBJECTS: In this study, we examine the relationship between job satisfaction(JS)
      and life satisfaction(LS) and the moderating effect of coping with JS and LS
      correlation (spillover) in order to obtain information of Human Resources
      Management for care workers in Health-Social service facilities. METHODS:
      Questionnaires were sent to individuals working in geriatric care facilities and
      responses were returned from a total of 612 females aged 20 to 63. Subjects were
      classified into 3 groups according to their age. Relationships between JS and LS
      were examined by multiple regression analysis and the moderating effect of coping
      behavior on spillover was examined by comparison of correlation coefficients of
      spillovers between the high score group and low score groups based on scores for
      coping behavior. RESULTS: Several significant causal interrelations were seen
      between JS and LS such as JS of "work time and shift" and LS of "health", but a
      moderating effect of coping with spillover was seen only in the middle age group
      (35-49). CONCLUSION: The results showed the need in some way to consider non-work
      life besides work life in the actual personnel programs of Health-Social service
      facilities, and indicated that relationships between coping and spillover depend
      on the age.

PMID- 11831023
TI  - [A study of the relation between providing healthcare information and behavior
      changes of people in Japan. Parental behavior changes after receiving information
      about the sudden infant death syndrome].
AB  - OBJECTIVE: Considering the lack of evidence concerning the relationship between
      providing healthcare information and behavior of people in Japan, we utilized a
      questionnaire to survey the parents of infants to evaluate behavior change after
      receiving information about the Sudden Infant Death Syndrome (SIDS). METHODS: A
      questionnaire about SIDS information was administered in 234 municipalities in
      Niigata, Gifu, Shizuoka, and Hiroshima Prefectures and in Yokohama City in
      November and December of 1999 to 14,879 parents who visited for the 18-month
      health examination of their children. The questionnaire did not ask for the
      participants' names. Logistic regression analysis was used to study the
      connection between behavior change and SIDS information sources. RESULTS: 10,900
      parents returned the questionnaire to give a 73.3% response rate, 19.0% of these
      receiving information about SIDS risk factors from hospitals or clinics, 3.7%
      from public health centers, and 9.2% from their friends. More received
      information from the mass media such as TV programs, which provided the main
      source for 71.1% of the parents. The degree of behavior change was evaluated
      after adjustment for variables concerning a variety of information sources and
      other appropriate factors such as the age and sex of parents and the number of
      their children. We found that receiving information from hospitals or clinics
      significantly influences behavior changes for all kinds of risk factors.
      Information from public health centers, baby-care groups, and friends influenced
      behavior changes relevant to the risk factors for feeding methods, sleeping
      position, and parents' smoking. There was no relation between receiving
      information from the mass media and behavior change of parents. CONCLUSIONS: The
      mass media provide far more information than do medical facilities, public health
      centers, baby-care groups and personal contacts but the latter played much more
      effective roles in making parents change their baby care behavior. These results
      point to an obvious discrepancy between efficiency in providing information and
      the degree of behavior change elicited. We should thus take the source of
      information and the target population into consideration when we examine the best
      way to provide healthcare information for people in the future.

PMID- 11831024
TI  - [A survey on attitudes and practice concerning International Health].
AB  - OBJECTIVE: A survey was conducted to help understanding of the attitudes and
      practice of Japanese medical students concerning "International Health".
      MATERIALS AND METHODS: One thousand seven hundred and ninety six students from
      eleven medical schools responded in the questionnaire study. One thousand and
      ninety seven were males and 699 were females with average ages of 22 and 21
      years, respectively. RESULTS: 32.3% of the students answered that they have/had
      an interest in "International Health". About half of the students answered that
      they wanted to have a lecture on "International Health" and they also had a
      willingness to engage in activities for "International Health" someday. Further,
      4% of the students had experience of participation in activities related to
      "International Health". Female students showed that they have a stronger
      willingness to take part in the "International Health activities" than males.
      CONCLUSION: Human resources that can work in the field of international
      cooperation are required because ODA from Japan has ranked first in the world for
      nine years in succession. However, the willingness to participate in
      "International Health activities" among students decreased conversely with their
      years of learning in medical school. This result might be a basic material when
      we look at the education toward "International Health" in the medical school.

PMID- 11831025
TI  - [Recent advances in Alzheimer's disease].

PMID- 11831026
TI  - [Degradation of extracellular matrix by matrix metalloproteinases and joint
      destruction].

PMID- 11831027
TI  - [A variety of functions of conventional and neuronal Shc adapter molecules in
      phosphotyrosine-mediated signalings].

PMID- 11831028
TI  - [Functions of guanidino compounds in brain].

PMID- 11831029
TI  - [Extracellular protein secretion signal of gram-negative bacterial ABC-exporter].

PMID- 11831031
TI  - [Possibility of micromachine technology in the field of biochemistry].

PMID- 11831030
TI  - [ADAMTS family--new extracellular matrix degrading enzyme].

PMID- 11831032
TI  - [Biosynthesis and intracellular transport of sphingolipids in mammalian cells].

PMID- 11831033
TI  - [Current studies on mechanisms of sex determination and sex differentiation with
      the ZW sex chromosomes of birds: comparison with studies on mammalian systems].

PMID- 11831034
TI  - [The role of membrane microdomain in signal transduction].

PMID- 11831035
TI  - [Band 3: expanding knowledge on its functions].

PMID- 11831036
TI  - [A novel type protein, Bcnt, that includes the region derived from a long
      interspersed nucleotide element].

PMID- 11831037
TI  - [On-chip single-cell cultivation system].

PMID- 11831038
TI  - [Functional genomic analysis by RNA interference].

PMID- 11831039
TI  - The sports medicine kit: basics of the bag.

PMID- 11831040
TI  - The preparticipation physical examination: a pediatrician's responsibility.

PMID- 11831041
TI  - Performance-enhancing drug use in the young athlete.

PMID- 11831042
TI  - Eye injuries in the young athlete: a case-based approach.

PMID- 11831043
TI  - Common infections in the young athlete.

PMID- 11831044
TI  - Sideline medical emergencies in the young athlete.

PMID- 11831045
TI  - A pediatrician's view. Changing of the guard.

PMID- 11831046
TI  - Sideline orthopedic emergencies in the young athlete.

PMID- 11831047
TI  - The professional team physician, 1984--present.

PMID- 11831049
TI  - A client-centered approach to family planning: the Davao project.
AB  - The reproductive health approach to family planning shifts the focus of service
      provision from macro-level demographic objectives to meeting clients' needs.
      Little field experience exists to date, however, to indicate how to implement
      this approach. This study describes a field project in Davao del Norte and
      Compostela Valley provinces in the Philippines that implemented the reproductive
      health approach on a quasi-experimental basis. The intervention was designed to
      address clients' self-defined reproductive needs by providing them with relevant
      and accurate information and services of good quality. It consisted of two
      components: Providers were trained in information exchange at fixed clinics, and
      supervisors were trained in facilitative supervision. The results presented here
      indicate that the client-centered intervention was successful in enhancing
      service providers' knowledge and improving the content of information exchange
      between providers and clients. One provincial health officer has expanded the
      intervention throughout his province, while other provinces are interested in
      duplicating the model.

PMID- 11831048
TI  - Premarital sex, schoolgirl pregnancy, and school quality in rural Kenya.
AB  - Using data from nearly 600 adolescents aged 12-19 in combination with data
      collected from 33 primary schools that the adolescents attended, this report
      explores whether certain aspects of the school environment affect the initiation
      of premarital sex among girls and boys in three districts of Kenya. The results
      suggest that, although neither the school nor the home appears to influence
      whether boys engage in sex prior to marriage, for girls, a school characterized
      by a gender-neutral atmosphere appears to reduce the risk of their engaging in
      premarital sex. Furthermore, although policymakers in Kenya are clearly concerned
      with the problem of "schoolgirl pregnancy," the data indicate that in this
      sample, pregnancy is not the primary reason that girls leave school.

PMID- 11831050
TI  - Organizing a public-sector vasectomy program in Brazil.
AB  - Although models of high-quality family planning services for men exist in Latin
      America, few if any have been organized within the complex and resource
      constrained national public health systems. This study provides evidence from the
      Santa Barbara project in southern Brazil showing how vasectomy was introduced
      into the municipal health system. It demonstrates that once the necessary
      operational and quality-of-care improvements were in place, and sufficient
      political and technical support existed to proceed, it was possible to establish
      low-cost, well-used, and sustainable vasectomy services free of charge. The
      findings show that careful attention to the development of strong technical
      competence and an informed choice process resulted in high user satisfaction.
      Focus-group discussions with men who underwent vasectomy indicate that they had
      no objection to being served in the context of a women's health center and that
      they act as opinion leaders who draw an increasing clientele to the service.

PMID- 11831051
TI  - Changes in contraceptive use in Bulgaria, 1995-2000.
AB  - Comparison of results from national surveys conducted in Bulgaria in 1995 and
      2000 reveal little overall change in use of modern contraceptives. Dramatic
      increases occurred, however, among women younger than 25 who entered their
      reproductive period after the end of the state socialist period. This finding
      suggests that contraceptive gains in the country will come largely as a cohort
      replacement process. From these data, no separate program impact appears for
      special clinics established to provide direct, subsidized delivery of modern
      contraceptives to women in selected cities. The special clinics opened in cities
      where contraceptive use was already above the national average. During these five
      years, other cities lacking special clinics managed to gain in prevalence of
      modern contraceptive use, leaving a relatively homogenous urban-rural difference
      in levels of use throughout the country.

PMID- 11831052
TI  - An evaluation of the "Entre Nous Jeunes" peer-educator program for adolescents in
      Cameroon.
AB  - A quasi-experimental design is used in this study to evaluate the "Entre Nous
      Jeunes" peer-educator program to promote STI/HIV-preventive behaviors in
      Nkongsamba, Cameroon. The main objective of the study is to assess whether the
      young people exposed to a peer educator gained greater knowledge and practiced
      more protective behaviors than did those in the control community and those who
      were not exposed. During the 18-month intervention period, the peer educators
      were able to reach a large number of young people, specifically those who were
      sexually experienced and in need of reproductive health information. Multivariate
      analyses indicate that contact with a peer educator is statistically
      significantly associated with greater spontaneous knowledge of modern
      contraception, the symptoms of sexually transmitted infections, and greater use
      of modern contraceptives, including the condom. In the absence of a peer
      education program, current contraceptive use in the intervention community would
      have been significantly lower.

PMID- 11831053
TI  - An ecologic analysis of maternal mortality ratios.

PMID- 11831054
TI  - Kazakhstan 1999: results from the Demographic and Health Survey.

PMID- 11831055
TI  - Nigeria 1999: results from the Demographic and Health Survey.

PMID- 11831056
TI  - [Coexistence of hereditary coproporphyria and porphyria cutanea tarda: a new form
      of dual porphyria].
AB  - BACKGROUND: Dual porphyrias are characterized by two independent disturbances of
      porphyrin metabolism. PATIENT AND METHODS: At first a porphyria cutanea tarda was
      diagnosed in a 26-year-old female with back pain and red urine. Later a
      hereditary coproporphyria was ascertained by additional examinations. The
      metabolites of porphyrin metabolism were analyzed chromatographically. The
      activities of coproporphyrinogen oxidase and uroporphyrinogen decarboxylase were
      determined in blood cells. Molecular analysis was carried out by denaturing
      gradient gel electrophoresis followed by direct sequencing. RESULTS: Excessive
      porphyrinuria of 3,128 nmol/24 h (normal < 165 nmol/24 h) with dominance of uro-
      and heptacarboxyporphyrin (75% of total porphyrins) indicated that the patient
      suffered from porphyria cutanea tarda. The course of the examination showed an
      alteration of the constellation with dominance of urinary and fecal
      coproporphyrin isomer III, which is characteristic for hereditary coproporphyria.
      Porphyrin precursors and porphyrins increased under the application of
      ethinylestradiol-cyproteronacetat. The dominance of coproporphyrin III stayed
      constant in feces besides enhanced urinary uro- and heptacarboxyporphyrin. The
      activity of the coproporphyrinogen oxidase was diminished to 35%. The
      uroporphyrinogen decarboxylase in erythrocytes was normal. The mother and both
      sisters were recognized as heterozygous gene carriers of hereditary
      coproporphyria in the latent phase by enhanced coproporphyrin with isomer I/III
      inversion in feces and decrease of the coproporphyrinogen oxidase activity to
      about 50%. Molecular analyses resulted in a point mutation at exon 4 (854C-->T),
      which revealed in an amino acid exchange (P258L) in the coproporphyrinogen
      oxidase protein. CONCLUSION: The hereditary coproporphyria is caused by a new
      mutation in the coproporphyrinogen oxidase gene in the case of a dual porphyria
      with co-existence of porphyria cutanea tarda and hereditary coproporphyria. The
      sporadic, hepatic porphyria cutanea tarda Type I is induced by estrogens. The
      large excretory variations reflect the influence of hormonal factors on the
      porphyria process of hereditary coproporphyria and porphyria cutanea tarda.

PMID- 11831057
TI  - [Gastrointestinal manifestations of HIV infection].
AB  - BACKGROUND: HIV-related immunodeficiency particularly affects the mucosal immune
      system. Therefore, the gastrointestinal tract is target to numerous HIV
      associated diseases. Since the introduction of highly active antiretroviral
      therapy (HAART) the prevalence of HIV-related secondary diseases has
      significantly declined. Their clinical appearance, however, remained unchanged.
      RESULTS: This review summarizes the most important gastrointestinal complications
      of HIV disease and their treatment focusing on key symptoms and signs. In
      addition, appropriate diagnostic strategies are proposed. CONCLUSIONS: Given the
      high number of secondary gastrointestinal diseases and their potential impact on
      prognosis and quality of life of HIV-infected patients, it is important to employ
      an effective diagnostic and therapeutic approach to these patients. Control of
      HIV replication and immune deficiency by HAART offers new therapeutic options in
      cryptosporidiosis and microsporidiosis and is crucial for the long-term
      prevention of opportunistic enteric infections or HIV-related malignancies.

PMID- 11831058
TI  - [Risk of infection and preventative strategies in the domestic environment of
      immunosuppressed hematologic oncology patients].
AB  - BACKGROUND: To date, the problem of infectious risks in the domestic environment
      has not been focused as intensively as that in the clinical environment. Due to
      increasing costs in health care, there are considerations to intensify outpatient
      treatment models, e.g., for hematology-oncology patients, enhancing the
      importance of this problem. PREVENTIVE MEASURES: Based on a review of the
      relevant literature, this article summarizes the potential infectious risks for
      immunosuppressed patients in the domestic environment and gives recommendations
      for control measures. The topics of daily life are considered in detail including
      special risks of leisure activities. For most of the risks, evidence-based
      recommendations cannot be given. CONCLUSION: The scope of these recommendations
      is to support the attending physician when advising the immunocompromised patient
      and to give suggestions for possible control measures to the patient.

PMID- 11831059
TI  - [Fever after travel to the tropics].
AB  - BACKGROUND: Fever in travellers returning from the tropics may be caused not only
      by tropical infection but also by travel associated non-specific infections and
      cosmopolitan infective diseases. DIAGNOSTIC PROCEDURE: A rational out-patient
      step by step procedure needs clinical data and a small account of laboratory
      investigations. A parasitological screening is mandatory. The results refer to
      parasitological, bacterial or viral diseases. Epidemiological aspects of the
      travelled country and incubation periods of tropical or other diseases have to be
      considered. CONCLUSIONS: Plasmodium falciparum infection has to be excluded first
      because of vital damage. Following malaria (30%) respiratory infections (11%) are
      common. Fever as a symptom of non-infective disease occurred in 9%. Other
      diseases (typhus, Dengue fever, tuberculosis) are rare but have to be considered.

PMID- 11831060
TI  - [Manifestation of hyper-IgE syndrome in advanced HIV-1 infection].
AB  - BACKGROUND: The classical triad of Job's syndrome (Hyper-IgE syndrome), a
      congenital immunodeficiency disorder, includes recurrent "cold" abscesses,
      pneumonias and extreme elevations of the serum IgE concentration. CASE REPORT: A
      49-year-old HIV-1 infected patient with a viral load of 268,852 copies/ml plasma
      and a CD4+ T lymphocyte concentration of 2 cells/microliter blood was admitted to
      our clinic for antibiotic therapy and incision and drainage of several large
      abscesses. The patient suffered for approximately 5 years from recurrent
      pneumonias, abscesses and multiple allergies. The serum IgE level was over 100
      fold elevated and, after analysis of archived serum samples, had not been
      influenced by fluctuations in the plasma viral load or changes in the CD4+ T
      lymphocyte concentration in previous years. No stigmata of Job's syndrome were
      present prior to the patient's HIV-1 infection. Observations on other patients
      with AIDS and recurrent abscesses suggest that in these patients
      hyperimmunoglobulinemia E is related to a cytokine class switch from a TH1 to a
      TH2 profile as CD4+ T lymphocytes are depleted. CONCLUSIONS: Following CD4+ T
      lymphocyte depletion, it has been rarely documented that HIV-1 infected patients
      may develop clinical symptoms and a hyperimmunoglobulinemia E, similar to
      patients with the congenital immunodeficency of Job's syndrome.

PMID- 11831061
TI  - [Reynolds syndrome--a rare combination of 2 autoimmune diseases].
AB  - HISTORY AND CLINICAL FINDINGS: Since several years, two women, 69 and 75 years of
      age, developed a paroxysmal blanching of the fingers on both hands. The attacks
      were accompanied by local pain and followed by a short period of cyanotic
      discoloration. INVESTIGATIONS: The diagnosis of progressive systemic sclerosis
      was reached by skin biopsies, immunoserological profile and significant blood
      vessel alteration at the proximal nail fold (capillary microscopy) in both
      patients. Initial esophageal sclerosis was only found in one patient. Both women
      were conspicuous by sonographically proven hepatomegaly, elevated hepatic
      serological parameters, in particular aP and GGTP. Positive AMA titers of M2
      specificity and specific features in liver biopsies yielded the additional
      diagnosis of primary biliary cirrhosis). TREATMENT AND COURSE: One of the women
      was treated by pentoxifylline and nifedipine in order to improve rheology. Both
      received physiotherapeutic assistance. Primary biliary cirrhosis was treated with
      ursodeoxycholic acid which led to normalization of the cholestatic parameters.
      CONCLUSIONS: Reynolds' syndrome constitutes the coexistence of progressive
      systemic sclerosis and primary biliary cirrhosis. It remains unknown whether or
      not there is a constant time-related sequence of the clinical manifestations of
      the two immunogenetically determined disorders. However, it is remarkable that
      the affected elderly women described so far had Raynaud's symptoms long before
      the final diagnosis of Reynolds' syndrome was settled. Thus, the Raynaud's
      phenomenon is an early clinical symptom for the evolution of a Reynolds'
      syndrome. By experience, the coincidence of progressive systemic sclerosis and
      primary biliary cirrhosis seems to be a favorable factor concerning the
      progression of primary biliary cirrhosis. So, an elderly woman with recently
      manifested progressive systemic sclerosis should alert the physician to a
      concomitant primary biliary cirrhosis.

PMID- 11831062
TI  - [Therapy of Zenker's diverticulum].

PMID- 11831063
TI  - [Risk Management: concepts and chances for public health].
AB  - BACKGROUND: Errors are a common problem in medicine and occur as a result of a
      complex process involving many contributing factors. Medical errors significantly
      reduce the safety margin for the patient and contribute additional costs in
      health care delivery. SYSTEM APPROACH: In most cases adverse events cannot be
      attributed to a single underlying cause. Therefore an effective risk management
      strategy must follow a system approach, which is based on counting and analysis
      of near misses. The development of defenses against the undesired effects of
      errors should be the main focus rather than asking the question "Who blundered?".
      Analysis of near misses (which in this context can be compared to indicators)
      offers several methodological advantages as compared to the analysis of errors
      and adverse events. Risk management is an integral element of quality management.

PMID- 11831065
TI  - [Molecular therapy of chronic myeloid leukemia--a new era in the treatment of
      malignant diseases].

PMID- 11831064
TI  - [Dyspepsia and Helicobacter pylori infection in employees of a large industry.
      Results of a prospective BASF Helicobacter pylori prevention campaign].
AB  - BACKGROUND: The role of Helicobacter pylori (H. pylori) infection in dyspepsia is
      controversial. In the course of a health initiative within a large industrial
      corporation, we investigated the prevalence of both dyspepsia and positive H.
      pylori serology and the outcome of eradication therapy in symptomatic H. pylori
      positive employees. TEST PERSONS AND METHODS: H. pylori serology (IgG ELISA) was
      determined in 6,143 employees of BASF AG Ludwigshafen/Germany who were also asked
      to complete a standardized health history administered by a physician. Peptic
      ulcer disease (PUD) and dyspepsia subgroups were defined based on past medical
      history and symptom profiles using the criteria of Heading. Upper GI endoscopy,
      abdominal ultrasound and eradication therapy (Italian Triple Therapy) was
      recommended for symptomatic H. pylori positive individuals. The prognostic value
      of antibodies against CagA and VacA was evaluated in 37 and 39 employees with PUD
      and non-ulcer dyspepsia (NUD) confirmed by endoscopy, respectively. RESULTS: Of
      6,143 employees, 1,255 (20.4%) were classified as dyspeptic, 492 (39.2%) of whom
      were H. pylori positive. The seroprevalence of H. pylori in asymptomatic
      employees was 35.8%. There were no significant differences in H. pylori
      seroprevalence among dyspepsia subgroups (reflux only, dysmotility only,
      reflux/dysmotility, ulcer-like and non-specific). However, individuals reporting
      severe dyspeptic symptoms were significantly more likely to be H. pylori positive
      (OR 2.09, CI 1.43-3.05). The seroprevalence of CagA and VacA was not
      significantly different among employees with NUD compared to referents or among
      employees with NUD compared to those with PUD. 330 (72%) of 458 employees with
      dyspepsia received eradication therapy, 128 persons refused therapy. Based on a
      12-month follow-up of 402 individuals (300 of whom had received therapy),
      eradication success was 81.5% as judged by serology. Of the successfully treated
      employees, 33.2% reported a total absence and 42.8% reported a decrease in
      symptoms. Among the employees who refused therapy, the corresponding percentages
      were 37.3% and 16.7%, respectively. An increase in reflux complaints was not
      observed among treated employees. CONCLUSION: In a large active employee
      population, at most a very weak association was observed between the prevalence
      of H. pylori seropositivity and dyspepsia. Frequent and severe dyspeptic symptoms
      were associated with an increased rate of H. pylori seropositivity. The analysis
      of the virulence factors is not particularly helpful in discriminating PUD or
      NUD. Eradication of H. pylori infection leads to a decrease in dyspeptic symptoms
      after 12 months, but not more often to their complete absence compared to
      untreated individuals.

PMID- 11831066
TI  - [Therapy of Philadelphia chromosome positive acute lymphatic leukemia (Ph+ ALL)
      with an inhibitor of abl-tyrosine kinase (Glivec)].
AB  - BACKGROUND: Ph+/bcr-abl positive ALL has the worst prognosis of all subgroups of
      ALL; only a small minority of patients are cured with currently established
      treatment regimens. The central pathogenetic role of the constitutively activated
      and deregulated abl-tyrosine kinase that is a direct consequence of the bcr-abl
      rearrangement opens the possibility of treating this disease using a molecularly
      targeted approach. The recent development of the selective abl-tyrosine kinase
      inhibitor Glivec (formerly STI571) opens the opportunity of blocking the signal
      transduction pathways critically involved in bcr-abl induced leukemogenesis.
      TREATMENT RESULTS AND CONCLUSIONS: Glivec exerts a significant anti-leukemic
      effect in patients with Ph+ ALL, with a remarkably favorable toxicity profile.
      This enables transfer of a subset of the responding patients to a potentially
      curative allogeneic stem cell transplantation. Despite promising initial
      therapeutic effects, treatment with Glivec alone is not able to achieve cures in
      the majority of patients with relapsed or refractory Ph+ ALL. The earlier
      administration of Glivec in patients with "de novo" ALL as well as combining it
      with other treatment modalities is likely to improve treatment results. The
      identification of specific resistance mechanisms towards Glivec should provide
      valuable information regarding the development of clinical strategies to
      circumvent resistance. Glivec can already be considered an important element in
      the treatment of Ph+ ALL, although the most effective ways of employing this
      novel agent remain to be established.

PMID- 11831067
TI  - [Bcr-Abl inhibition as molecular therapy approach in chronic myeloid leukemia].
AB  - BACKGROUND: Bcr-Abl, a constitutively activated tyrosine kinase, is a product of
      the Philadelphia chromosome (Ph) translocation t(9;22), present in nearly all
      cases of chronic myeloid leukemia (CML) and in about 20% of cases with acute
      lymphoblastic leukemia. CML, a myeloproliferative disorder, progresses through
      three phases--chronic phase, accelerated phase and blast crisis. Current
      therapies include drug regimens such as interferon alpha, hydroxyurea, busulfan
      or allogeneic bone marrow transplantation, the only curative treatment for CML,
      which is, however, limited to younger patients with a suitable donor. INHIBITION
      OF BCR-ABL AS EFFECTIVE AND SELECTIVE TREATMENT IN CML: In vitro studies and
      studies in animal models have shown, that Bcr-Abl is the molecular cause CML.
      Therefore inhibition of the Bcr-Abl tyrosine kinase is expected to be an
      effective and selective treatment modality for CML. STI571 was shown to be a
      competitive inhibitor at the ATP-binding site of the Bcr-Abl tyrosine kinase, the
      platelet-derived growth factor receptor and c-kit tyrosine kinases. It shows
      effects on proliferation and survival of Bcr-Abl-expressing cells without
      affecting normal cells or Ph-negative leukemic cells. DRUG RESISTANCE TO STI571:
      Several mechanisms of resistance have been identified from in vitro studies with
      Bcr-Abl-positive cell lines. Mechanisms include amplification or overexpression
      of Bcr-Abl or an increased expression of P-gly-coprotein. In a mouse model the
      binding of STI571 to acidic alpha 1 glycoprotein (AAG) has been proposed to be
      involved in the development of STI571 resistance. Recent studies with clinical
      samples from resistant patients have shown that point mutations in the kinase
      domain of Bcr-Abl play a role in the development of resistance to STI571.
      CONCLUSIONS: STI571 is a promising example of a moleculary targeted therapy
      directed towards the molecular cause of CML. To maximize the therapeutic value
      and to avoid the induction of resistance, a combination of the drug with other
      chemotherapies should be considered. According to its pharmacological profile,
      STI571 could also be useful in the treatment of tumors with deregulated PDGF
      receptor or c-kit signaling, e.g., in chronic myelomonocytic leukemia with a
      t(5;12) chromosomal translocation or in cases with gastrointestinal stromal
      tumors (GIST). STI571 shows a new paradigm in the development of new targeted
      therapies for the treatment of malignant diseases.

PMID- 11831068
TI  - [Results up to now of administration of STI-571 (Glivec) in recurrence after
      allogenic and autologous stem cell transplantation in chronic myeloid leukemia].
AB  - BACKGROUND: Gleevec (STI-571) is s selective inhibitor of the bcr/abl tyrosine
      kinase. Recent phase I and phase II studies in patients with bcr/abl positive CML
      and ALL showed a low rate of grade III/IV toxicity and good clinical efficacy.
      This report describes the preliminary results in patients relapsing post
      autologous or allogeneic peripheral blood stem cell transplantation. The focus of
      this analysis will include toxicity, feasibility and clinical efficacy. THERAPY
      AND RESULTS: 18 of 18 patients with cytogenetic and/or hematologic relapse in
      chronic phase CML post autologous stem cell transplantation achieved a complete
      hematologic remission upon therapy with Gleevec. The cytogenetic response rate
      was 75% with a complete cytogenetic response rate of 50%. After allogeneic stem
      cell transplantation, patients in cytogenetic or hematologic relapse also
      experienced high hematologic and cytogenetic response rates upon therapy with
      Gleevec. In these patients, Gleevec was shown to induce mixed chimerism. Overall,
      Gleevec was well tolerated after autologous and allogeneic stem cell
      transplantation. Most common side effects were mild to moderate gastrointestinal
      discomfort and edema. No symptoms of chronic extensive or > grade I acute GvHD
      could be observed. Hematologic toxicity was dependent on stage of disease. Grade
      III/IV granulocytopenia and/or thrombopenia could be observed in 50% of patients
      with transformed phases of CML. Management of these patients required frequent
      controls of peripheral blood counts and transfusion of blood products.
      CONCLUSION: These results show a new approach in treatment of patients with
      Philadelphia-chromosome-positive leukemia relapsing post autologous or allogeneic
      stem cell transplantation. Gleevec is able to induce mixed chimerism without
      induction of severe GvHD. The data suggest that early start of STI-571 therapy in
      MRD-positive patients is a promising approach. Recently, a multicenter phase II
      study to evaluate the toxicity and efficacy of Gleevec in CML patients with
      minimal residual disease post allogeneic transplantation was started.

PMID- 11831069
TI  - Treatment of inoperable gastrointestinal stromal tumor (GIST) with Imatinib
      (Glivec, Gleevec).
AB  - BACKGROUND: Imatinib (STI571 or Glivec, Novartis) is a new type of tyrosine
      kinase inhibitor that selectively inhibits various tyrosine kinases including
      ABL, BCR-ABL, KIT and PDGF receptors. IMATINIB IN CML: Earlier studies have shown
      that Imatinib is highly effective in the treatment of chronic myeloid leukemia
      (CML), which is characterized by translocation of chromosome material from
      chromosome 9 to chromosome 22 with formation of the so-called Philadelphia
      chromosome. During this process, an abnormal fusion protein, tyrosine kinase BCR
      ABL, is formed. In a phase I study it was shown that a daily dose of 300 mg
      Imatinib resulted in a complete hematological response in almost 98% of the
      patients. IMATINIB IN GIST: Gastrointestinal stromal tumors (GIST) are also
      suitable indications for treatment with Imatinib, the prerequisite being
      overexpression by the tumor of c-KIT (CD117). This tumor entity responds
      extremely poorly to polychemotherapy. Initial case reports and various study
      approaches appear to indicate that treatment of GIST with Imatinib is a highly
      promising therapeutic option in this entity. Follow-up studies with FDG-PET have
      shown an appreciable decrease in uptake by tumor tissue, in some cases within
      only a few days, which may well indicate an inhibition of intratumoral metabolism
      and growth. Most patients with metastatic GIST achieve durable responses with
      imatinib, and the disappearance of cancer-related symptoms is often rapid.
      CONCLUSION: Imatinib is the first effective systemic therapy for advanced GIST.

PMID- 11831071
TI  - [Screening].

PMID- 11831070
TI  - [Drug therapy of chronic myeloid leukemia].
AB  - STANDARD TREATMENT: According to the evidence-based guidelines for the therapy of
      chronic myelogenous leukemia (CML) the combination of interferon alpha (IFN) and
      hydroxyurea with or without low dose ara-C is the standard treatment for chronic
      phase CML, if no allogeneic stem cell transplantation is requested. STI571: In
      cases of IFN failure the new tyrosine kinase inhibitor STI571 (Glivec) shows high
      response rates. STI571 specifically inhibits the BCR-ABL fusion protein which is
      pathogenetically relevant for CML and shows abnormal tyrosine kinase activity.
      91% of all CML patients in chronic phase achieve a hematologic remission within
      11 months and 55% cytogenetic remission. In blast crisis, 29% achieve hematologic
      remission which may be durable. CONCLUSION: The available data represent response
      rates. Until survival data are available, the evidence-based recommendations will
      remain valid.

PMID- 11831072
TI  - [Risk, disease and prioritization].

PMID- 11831073
TI  - [Screening--what information should potential participants receive?].

PMID- 11831074
TI  - [Screening. What documentation should be required?].

PMID- 11831075
TI  - [Colorectal cancer screening].

PMID- 11831077
TI  - [Screening for abdominal aortic aneurysm].

PMID- 11831076
TI  - [Prostatic cancer screening].

PMID- 11831078
TI  - [Screening for hepatitis B].

PMID- 11831079
TI  - [Screening for chlamydia among sexually active young people].

PMID- 11831080
TI  - [Psychological reactions connected to screening participation--illustrated by
      breast cancer screening].

PMID- 11831081
TI  - [Screening for lung cancer with low-dosage CT].

PMID- 11831082
TI  - [Cervical cancer screening].

PMID- 11831083
TI  - [Testing for human papillomavirus in cervical cancer screening].

PMID- 11831084
TI  - [Recommendations on cancer screening in the European Union. Advisory Committee on
      Cancer Prevention].

PMID- 11831085
TI  - [General health check ups].

PMID- 11831086
TI  - [Consequences of uncertainty and overdiagnosis in screening].
AB  - Uncertainty in screening has consequences for real people's lives. This article
      describes the various types of uncertainty, such as false results, diagnostic
      probabilities, consistency in diagnosing, bias in screening research, cumulative
      risk of false results over a life span, and the potential risk with certain
      procedures. Overdiagnosis as an unrecognised cause of harm in screening is also
      discussed. Every offer of a screening contains a hidden message, saying: "you are
      not able to assess your own health; even if you think you are healthy, you may
      have an unknown disease". Hence, the worst effect of screening might be the
      undermining of people's confidence in their ability to assess their own health.
      If the concept of screening conveys the idea in the population that only medical
      examinations can say anything about health status, it implies the use of many
      other activities in the health care system to convince healthy people that they
      are still healthy.

PMID- 11831087
TI  - [Selective screening for hepatitis B of pregnant women with previous acute
      hepatitis B].
AB  - INTRODUCTION: The aim of this study was to examine the performance of the
      selective screening programme for hepatitis B (HB) in pregnancy. MATERIAL AND
      METHODS: Notifications of women with acute HB in the period 1981-1997 were traced
      in the National Birth Registry. For children born after the HB event, details of
      the records on the results of HB testing and other information about the previous
      HB disease were obtained from the maternity wards. RESULTS: The study group
      comprised 129 mothers and their 185 deliveries. Of the 185 deliveries, 31% took
      place without any information about the previous HB disease and 51% without
      testing for HB. When these results were related to the information on the
      notification form regarding the mode of transmission, it transpired that the
      proportion with an unknown mode of transmission was higher in those with no
      information about previous HB in the maternity records than in those with
      information (43% vs 18%). Of 18 infants delivered of 13 chronically infected
      mothers, four did not receive the proper immunoprophylaxis. DISCUSSION: The study
      shows that a selective screening programme as used in Denmark is not good enough
      to identify pregnant women at risk of chronic HB infection. The main problems are
      related to failure to identify risk factors of hepatitis B transmission.
      Screening and treatment failure in siblings delivered of chronically infected
      mothers was also found. As in most other western countries a general programme
      should replace the selective screening programme.

PMID- 11831088
TI  - [Mammographic screening in the municipality of Copenhagen 1991-1997. Evaluation
      of the preoperative assessment].
AB  - INTRODUCTION: A biennial mammography screening programme started for all women
      aged 50-69 in the municipality of Copenhagen, Denmark, in April 1991. The aim of
      the present study was to evaluate the quality of the preoperative diagnostic
      assessment for women recalled for further examination. Quality indicators were:
      validity of the fine-needle aspiration cytology, rate of malignant to benign
      surgery, and frequency of one-step surgery for malignant lesions. MATERIAL AND
      METHOD: Database registries during the first three screening rounds from April
      1991 to March 1997 were studied retrospectively, for fine-needle aspiration
      cytology tests where surgical biopsy was also performed. RESULTS: In the period
      1991-1997, 4,111 women were recalled for clinical mammography and subsequently
      1,086 women underwent surgery. The use of the triple test in the preoperative
      assessment increased from 50% in the first screening round to 72% in the third.
      Throughout the period of evaluation, the number of inadequate fine-needle
      aspiration cytology (FNAC) was reduced from 32% to 6%. Inadequate FNAC from
      malignant lesions declined from 27% to 6%. The sensitivity of FNAC increased from
      67% to 90% and the accuracy from 60% to 81%. The malignant/benign ratio of
      surgery rose from 1.4 in the first screening round to 2.8 in the third. One-step
      surgery as definitive treatment was performed in 67% of malignant instances.
      DISCUSSION: The preoperative diagnostic assessment improved during the evaluation
      period. The triple test was used more often over time, the validity of FNAC and
      the malignant/benign ratio of surgery increased.

PMID- 11831090
TI  - [Perioperative stress response and postoperative morbidity/mortality].

PMID- 11831089
TI  - [Acceptance of mammographic screening by immigrant women].
AB  - BACKGROUND: The aim was to investigate compliance by ethnic groups to the
      mammography screening programme in the City of Copenhagen over six years and to
      look at developments over time. MATERIAL AND METHODS: Mammography screening has,
      since 1 April 1991, been offered free of charge to all women between 50 and 69
      years of age in the City of Copenhagen. Data on women born in Poland, Turkey,
      Yugoslavia, and Pakistan divided into five-year groups were compared to that of
      women born in Denmark and all other foreign-born women. Data from 1991 to 1997
      were grouped according to the mammography performed, the offer refused, or non
      appearance. RESULTS: Whereas 71% of Danish-born women accepted mammography,
      compliance by foreign-born women was significantly lower. The offer was accepted
      by 36% of Pakistanis, 45% of Yugoslavians, 53% of Turks, and 64% of Poles.
      Compliance fell in all ethnic groups with advancing age. Of the Danish women, 16%
      failed to keep the appointment. The corresponding percentages were 52 for
      Pakistanis, 48 for Yugoslavians, 41 for Turks, and 23 for Poles. The proportion
      of women who actively refused the offer was similar in all groups. The number of
      invited women fell during the period. CONCLUSIONS: The lower participation of
      women from the countries under study might have various explanations: among them
      the language barrier, procedure-related factors, and a lower incidence of breast
      cancer in the countries of origin.

PMID- 11831091
TI  - [Breast cancer screening--two years after].

PMID- 11831092
TI  - [Breast cancer screening].

PMID- 11831093
TI  - [Who does make up the standard?].

PMID- 11831094
TI  - Advances in the treatment of soft-tissue sarcomas.
AB  - Over 8000 newly diagnosed cases of sarcoma will occur in the United States this
      year. The family practitioner will encounter many soft-tissue masses, and the
      great majority of such masses will be benign. The clinician should maintain a
      high index of suspicion for lesions 5 cm or larger. Tissue diagnosis as well as
      accurate staging are important for optimal management. Limb salvage and improved
      prognosis are possible with the use of multimodality techniques. The goal in the
      overall management of soft-tissue sarcomas is a curative, yet functional,
      outcome. Adjuvant brachytherapy may be advantageous for patients who require but
      who are unable to receive daily external beam radiation. Treatment options,
      including some with targeted molecular therapies, are in the forefront of ongoing
      research.

PMID- 11831095
TI  - Divalproex as a calmative adjunct for aggressive schizophrenic patients.
AB  - BACKGROUND: Selection of appropriate pharmacotherapy for psychotic patients who
      exhibit dangerousness is an important issue. Divalproex is a fast-acting agent
      which appears to be safe and effective in such circumstances. The objective of
      the following inpatient study was to investigate divalproex as a pharmaceutical
      adjunct in treating agitated and/or violent, psychotic schizophrenic subjects.
      METHODS: For the purpose of comparison, 147 hospitalized patients were separated
      into violent (n = 60) and non-violent (n = 87) groups. In addition to
      antipsychotic drugs given to all subjects, divalproex was preferentially
      prescribed for the more dangerous patients (n = 40). The clinical status of
      demographics and parameters related to dangerousness in all participants was
      assessed to document differences during these admissions and for
      rehospitalization over one year. RESULTS: Divalproex was well tolerated; however,
      one individual developed a transient granulocytopenia. Its use in agitated and/or
      violent psychotic persons appears to have included a calmer, less dangerous
      hospital course, like that observed among their less disruptive counterparts.
      CONCLUSIONS: Divalproex seemed to have been helpful in this study at facilitating
      a more routine hospital course for agitated psychotic patients, similar to that
      of less overtly disturbed individuals. No significant adverse events were
      observed. The validity of this study is limited by its retrospective,
      uncontrolled nature.

PMID- 11831096
TI  - News for Kentucky physicians. HIPAA.

PMID- 11831097
TI  - Emergencies: how health care facilities are preparing for disasters.

PMID- 11831098
TI  - Effects of different disinfection and sterilization methods on tensile strength
      of materials used for single-use devices.
AB  - Driven by economic and time constraints, some medical centers and third parties
      are resterilizing single-use devices (SUDs) for reuse. The steam autoclave is
      quick, but most plastics used in SUDs cannot survive the temperature. Thus, a
      number of new methods of cleaning, disinfecting, and sterilizing these complex
      devices are being introduced on the market. The present study investigated the
      effects of a range of methods on the tensile strength of latex rubber, silicone
      elastomer, 2 different formulations of polyurethane, nylon, and high-density
      polyethylene (HDPE) specimens. The methods used were sodium hypochlorite bleach
      (Clorox), peracetic acid + hydrogen peroxide (Steris), formaldehyde gas
      (Chemiclave), low-temperature peracetic acid and gas plasma (Plazlyte), and low
      temperature hydrogen peroxide gas plasma (Sterrad). The results showed that
      silicone elastomer was minimally affected, whereas the strengths of nylon,
      polyethylene, and latex were reduced by some of the methods. Depending on the
      formulation, the strength of polyurethane either increased or decreased. The data
      demonstrated that disinfection and sterilization can affect the tensile strength
      of certain materials used in medical devices.

PMID- 11831099
TI  - Effect of lead connector design parameters on withdrawal strength of non-setscrew
      retention mechanism used in implantable pulse generators.

PMID- 11831100
TI  - Understanding the generational differences between "Boomers" and "Xers" in the
      workplace.

PMID- 11831101
TI  - Views from the field ... labeling methods run the gamut.

PMID- 11831103
TI  - The fundamentals of ... computed tomography.

PMID- 11831102
TI  - Surfing the Web: http, URLs, and HTML.

PMID- 11831104
TI  - Considering a midlife career change?

PMID- 11831105
TI  - Extubation following combined carotid endarterectomy and coronary artery bypass
      grafting.

PMID- 11831106
TI  - New components of the metabolic syndrome: culprits or bystanders?

PMID- 11831107
TI  - White blood cell count is associated with some features of metabolic syndrome in
      a very old population.
AB  - BACKGROUND AND AIMS: Although the association between white blood cell (WBC)
      counts and the risk of cardiovascular disease has been repeatedly described, its
      biological mechanism is still unclear. A significant correlation has been
      demonstrated in adults between WBC counts and some risk factors for coronary
      heart disease (CHD), including insulin resistance. The aims of this study were:
      1) to investigate the association between WBC count and some risk factors for
      atherosclerosis in a sample of octo-nonagenarians; and 2) to test the hypothesis
      of an association between WBC count and "metabolic syndrome", a clinical
      condition mediated by insulin resistance. METHODS AND RESULTS: The study involved
      160 free-living healthy octo-nonagenarians participating in the Val Vibrata Aging
      Project, whose WBC count, and anthropometric and metabolic parameters were
      measured using standardised methods. WBC count correlated positively with the
      logarithm of triglyceride, apoprotein B and glucose levels, and negatively with
      high-density lipoprotein cholesterol: the subjects with low high-density
      lipoprotein and high triglyceride levels had higher WBC count than normal
      subjects. The WBC count were significantly higher in the subjects with four or
      more of six features of metabolic syndrome than in those with three or less.
      CONCLUSIONS: The results of this study support the existence of a significant
      association between WBC count and some of the typical features of metabolic
      syndrome in very old subjects.

PMID- 11831108
TI  - The metabolic syndrome, smoking, and antibodies to oxidized LDL in 58-year-old
      clinically healthy men.
AB  - BACKGROUND AND AIM: The aim was to examine whether the metabolic syndrome (as
      recently defined), its various components, and smoking were associated with
      circulating antibodies to oxidized low-density lipoproteins (IgG- and IgM-Ox
      LDLAb) and malondialdehyde-treated LDL (IgG- and IgM-MDA-LDLAb) (ELISA) in a
      population sample of clinically healthy 58-year-old men (n = 391). METHODS AND
      RESULTS: LDL peak particle size (gradient gel electrophoresis) and antibody
      titers were measured in all patients. Trend analysis showed significantly higher
      IgG-Ox-LDLAb and IgG-MDA-LDLAb titers across the range of men with none of the
      criteria defining metabolic syndrome (n = 77), those with > or = 1 criterion (n =
      252) and those fulfilling the criteria (n = 62), which remained after adjustment
      for smoking. IgG-Ox-LDLAb was associated with plasma insulin, body mass index
      (BMI), the waist/hip ratio (WHR) and smoking. IgG-MDA-LDLAb was, in addition,
      related to diastolic blood pressure, serum triglycerides and a small LDL peak
      particle size. The IgM antibody titers only inversely correlated with smoking.
      CONCLUSIONS: High serum titers of IgG antibodies to oxidized LDL and MDA-treated
      LDL were associated with the metabolic syndrome and smoking. Several of the
      factors in the metabolic syndrome were related to the IgG antibody titers to
      modified LDL. The high degree of intercorrelation among these factors makes it
      difficult to clarify the independent role of any specific factor.

PMID- 11831109
TI  - Is a low fat diet the optimal way to cut energy intake over the long-term in
      overweight people?
AB  - Successful weight loss depends on maintaining a sustained negative energy
      balance. This can be achieved on diets with a normal (40% energy) fat content as
      well as on low fat diets. Using a 'modified fat' (MF) diet enriched with
      monounsaturated fat (MUFA), body weight may be lost either by calorie counting,
      or by allowing ad libitum food intake with careful food selection. In the latter
      approach high energy, high MUFA foods (predominantly olive oil, but also may
      include nuts and avocado) should contribute no more than 20% total energy to the
      diet, and other foods should be selected to minimise meal energy density. This
      can be achieved simply by the consumption of a wide variety of vegetables and
      whole grain cereal foods. It is also important to restrict foods high in
      saturated fat and to encourage regular exercise. Such a 'modified fat' low energy
      diet designed for weight loss should also contribute numerous health benefits in
      relation to improved metabolic control in Type 2 diabetes and reduced
      cardiovascular disease risk (as the diet is not only rich in MUFA but also in a
      range of dietary antioxidants and other bio-active phytochemicals).

PMID- 11831110
TI  - Alcohol consumption and mortality: is wine different from other alcoholic
      beverages?
AB  - BACKGROUND: Alcohol has been an integral part of the diets of many cultures for
      thousands of years, and formed the basis of early antiseptics. However, many
      health professionals have been loath to recommend its moderate consumption. Fears
      of increased risks of cancers, strokes and coronary heart disease (CHD), as well
      as its role in accidents, violence, psychological and social decline (when
      consumed in excess) meant that alcohol was viewed as generally detrimental to
      health. Recent reports have examined some of these fears and suggest that the
      moderate consumption of alcoholic beverages, particularly red wine, may actually
      protect against the development of CHD. Evidence for the influence of alcoholic
      drinks on strokes and cancer is less clear. OBJECTIVES: This review discusses the
      chemical differences between red wine and other alcoholic beverages and their
      possible effects on the development of CHD, stroke and cancer. DATA SYNTHESIS AND
      CONCLUSIONS: Both clinical and experimental evidence suggest that red wine does
      indeed offer a greater protection to health than other alcoholic beverages. This
      protection has been attributed to grape-derived antioxidant polyphenolic
      compounds found particularly in red wine.

PMID- 11831111
TI  - How should FCHL be defined and how should we think about its metabolic bases?

PMID- 11831112
TI  - Pharmacological treatment of insulin resistance in obesity.
AB  - AIM: To discuss new pharmacological possibilities for acting on the lipid
      metabolism abnormalities relating obesity, insulin resistance and arterial
      disease. DATA SYNTHESIS: Obesity is frequently associated with excess caloric fat
      dietary intake, especially in the form of fatty acids. An increased flux of fatty
      acids into muscle, liver and pancreas is probably a major cause of insulin
      resistance and possibly of pancreatic secretory disturbances. Liver exposure to
      fatty acid overload may also be the main reason for the atherogenic lipoprotein
      profile of insulin resistance and type 2 diabetes, which is characterised by
      prolonged post-prandial hypertriglyceridemia, high levels of large very low
      density lipoproteins (VLDL) and small, dense low-density lipoproteins (LDL), and
      a reduced number of apoAl-containing high-density lipoproteins (HDL). This
      lipoprotein profile may be the main contributor to the high prevalence of
      arterial disease in patients with type 2 diabetes. The treatment of type 2
      diabetes and insulin resistance in obese or non-obese subjects should therefore
      aim at normalising fatty acid fluxes because this can be expected to enhance
      insulin action and ameliorate the atherogenic lipoprotein abnormalities. The
      discovery of peroxisome proliferator-activated receptors (PPARs) and the
      elucidation of their function as master controllers of the genes involved in
      fatty acid metabolism have facilitated the development of potent modulating
      substances. Promising results have been obtained with the current generation of
      PPAR gamma ligands, but undesirable effects have also been reported. CONCLUSIONS:
      New knowledge concerning the structure and function of PPAR gamma and PPAR alpha
      is being used to develop non-TZD modulators with combined PPAR alpha and gamma
      actions in animal studies. This new generation of substances may offer a more
      balanced spectrum of activity that may be better suited for the treatment of the
      insulin resistance and type 2 diabetes frequently associated with obesity.

PMID- 11831113
TI  - Current status of imported parasitic infection among foreign workers in northern
      Taiwan (1999-2000).
AB  - In the present study, a simple, economic and practical technique was employed for
      stool examination. Of a total of 6,146 fecal samples from foreign workers in
      Northern Taiwan between 1999 and 2000 were examined, 615 were found to be
      positive for parasitic infection and the overall infection rate was 10%. Newly
      arriving foreign workers had a significantly higher infection rate (15%) than
      those who had worked in Taiwan for 6-12 months (8%). The foreign workers came
      from Indonesia, Philippines, Thailand, Malaysia, and Vietnam. Except for the
      small number of workers from Malaysia which was not included, the infection rate
      order by nationality was Vietnamese (21%) > Indonesian (13%) > Philippino (10%) >
      Thai (4%). The female examined workers were about 3-fold of males and their
      infection rate (11%) was also significantly higher than the males (5%). The order
      of rates by age was 20-30 years (11%) > 31-40 years (8%) > 41-50 years (5%).
      According to the species of parasites, 569 foreign workers were infected with 1
      species (9%) > with 2 species (0.7%) > with 3 species (0.1%). Totally, 14 species
      (10 helminths including 1 plant nematode, Heterodera and 4 protozoa; hookworm
      might include 2 or 3 species, but counted as one species here) were found, of
      which 10 species were pathogenic (9 helminths and 1 protozoa) and 4 non
      pathogenic. Foreign workers from Indonesia harbored 12 species of parasites >
      from the Philippines, 9 species > from Thailand, 8 species > from Vietnam, 7
      species.

PMID- 11831114
TI  - Positive association of ankylosing spondylitis with homozygous HLA-B2704, but
      protection with B2705 in Taiwan Chinese.
AB  - The study was undertaken to determine the effects of HLA-B27 subtypes on
      susceptibility to ankylosing spondylitis (AS) in Taiwan Chinese, a polymerase
      chain reaction-restrictive fragment length polymorphism (PCR-RFLP) method was
      developed for subtyping of HLA-B27. In this series, there are 62 patients with AS
      who were tested HLA-B27 positive serologically and 738 normal persons over the
      age of 65. Among the 738 normal controls, 42 (5.7%) were HLA-B27 positive. There
      were six (14.3%) homozygous for B2704, 18 (42.9%) heterozygous for B2704, 2
      (4.8%) double heterozygous for B2704 and B2705, one (2.3%) double heterozygous
      for B2704 and B2706, 2 (4.8%) homozygous for B2705, 11 (26.1%) heterozygous for
      B2705, and 2 (4.8%) heterozygous for B2706. In our patients with AS, 37 (59.7%)
      were homozygous for B2704 and 25 (40.3%) were heterozygous for B2704. The HLA-B27
      carrier rate in Taiwan healthy old persons is estimated at 5.7%. Susceptibility
      to AS is determined by homozygosity for B2704. However, B2705 may be an indicator
      of protection against AS in Taiwan Chinese.

PMID- 11831115
TI  - Mucin gene expression in gallbladder epithelium with black pigment stone
      ascertained by in situ hybridization.
AB  - Black pigment stones are usually found in patients with liver cirrhosis or
      hemolytic disease. Mucoglycoproteins are present in a significant amount in black
      pigment stones and contribute to the matrix of gallstones. Epithelium of stone
      containing gallbladders contains much more mucin than those without stones. In
      this study, we try to determine by in situ hybridization the mucin gene
      expression in black stone-containing gallbladders and try to find the diversity
      of mucin gene expression in gallbladders containing black pigment stones and
      those without stones. In situ hybridization with DIG-tailed oligonucleotides was
      performed on sections of paraffin-embedded tissues of gallbladders with black
      pigment stones (n = 10) and those without stones (n = 6) to identify the
      expression of MUC1, MUC2, MUC3, MUC4, MUC5B and MUC6 in gallbladder epithelium.
      The findings showed that (1) mRNA expression of MUC1, MUC3, MUC5B and MUC6 were
      found in all gallbladders with black pigment stones, while they were expressed in
      33.3%, 83.3%, 83.3% and 66.7% respectively in those without stones. They were
      expressed more strongly and extensively in gallbladders with stones when compared
      to those without stones. (2) MUC2 and MUC4 labeling were absent in gallbladders
      without stones, while they were present in 20% and 60% of gallbladders with black
      pigment stones, respectively. We conclude that MUC3, MUC5B and MUC6 were the main
      mucin gene expression in either gallbladder with or without stones. Altered mucin
      gene expression occurred in gallbladders with black pigment stones, such as the
      presence of MUC2 and MUC4 and increased expression of MUC1, MUC3, MUC5B and MUC6
      in black stone-containing gallbladders. The higher incidence and stronger
      labeling intensity of mucin gene expression of MUC2, MUC3, MUC5B and MUC6 in
      black stone-containing gallbladder may reflect abundant mucin content in these
      gallbladders. Increased expression of MUC2 and MUC4 in black stone-containing
      gallbladder epithelium indicated that intestinal metaplasia and altered mucin
      genes could occur in diseased gallbladders.

PMID- 11831116
TI  - The effect of combined 5-fluorouracil and dexamethasone on cultured human retinal
      pigment epithelial cells.
AB  - This study was designed to investigate the inhibitory effect of 5-fluorouracil (5
      FU) and dexamethasone (DEX) on the proliferation of human retinal pigment
      epithelial (RPE) cells in vitro. The human RPE cells (R-50 cell line) were
      cultured and exposed to various concentrations of combined 5-FU (0, 250, 500,
      1000, 2000 ng/ml) and DEX (0, 1, 10, 100, 200 micrograms/ml). The cells were
      incubated for 96 hr and the medium was changed every 48 hr to replenish the drug
      action. Cell viability was assessed using cell counting and trypan blue exclusion
      method. Tetrazolium salt, which can be metabolized by mitochondrial dehydrogenase
      to form a formazan dye, was used to assay cell proliferation. Treatment with 5-FU
      alone inhibited cell proliferation in a dose-dependent manner. The concentration
      of 5-FU that inhibited growth by 50% (IC50) was found to be 704.12 ng/ml. There
      was a bimodal effect of DEX on RPE cells--stimulation at low concentrations (1,
      10 micrograms/ml) and inhibition at high concentrations (100, 200 micrograms/ml).
      When the two drugs were combined, there was additive inhibition in the
      concentration of 200 micrograms/ml of DEX. These results indicate that a
      combination of 5-FU and DEX is no more effective in the inhibition of human RPE
      cells, except in combination with high concentrations of DEX (> or = 200
      micrograms/ml).

PMID- 11831117
TI  - Effect of ionic and nonionic contrast media on fibrinolysis in patients
      undergoing angiocardiography.
AB  - Very few investigators have studied the effect of contrast media on fibrinolysis.
      The results of those previous studies are contradictory and inconclusive. The
      purpose of this study was to evaluate the effect of ionic and nonionic contrast
      media on fibrinolysis in patients undergoing angiocardiography. Sixty-two
      patients randomly received either ionic contrast medium Hypaque-76 (n = 31) or
      nonionic contrast medium Ultravist-370 (n = 31). Plasma tissue plasminogen
      activator (t-PA), plasminogen activator inhibitor 1 (PAI-1), fibrinogen, and D
      dimer were measured before and 20 minutes after the procedures. A significant
      increase of PAI-1 levels was seen in the Ultravist group but not in the Hypaque
      group. The t-PA and fibrinogen levels remained virtually unchanged in both
      groups. A significant increase of D-dimer concentrations was observed in the
      Hypaque group but not in the Ultravist group. The results of this study may in
      part explain the reason that the ionic contrast media produce fewer
      thromboembolic complications than the nonionic contrast media during the cardiac
      catheterization.

PMID- 11831118
TI  - Factors attributing to the psychological recovery from the 1999 Taiwan earthquake
      among junior high school students: a focus group interview study.
AB  - The aim of this study was to evaluate the factors contributing to the
      psychological recovery from the 1999 Taiwan earthquake from the perspective of
      adolescents in Chungliao. A total of 22 junior high school students who had
      significant decrease of Impact of Event Scale (IES) scores in the follow-up
      period of 9 months were recruited to participate in one of three focus groups. By
      applying the method of focus group interviewing, adolescents' attributions of
      factors relating to the improvements of psychological reactions were collected.
      All interviews were tape-recorded and the transcripts were approached by content
      analysis. Four major factors contributing to psychological recovery from the
      earthquake are clustered: (1) self-healing effect as time passed away; (2)
      assistance from people of the non-afflicted areas; (3) being engaged in interests
      in leisure time; and (4) other important events happening after the earthquake.
      Several factors contributed to the psychological recovery of adolescents from the
      experience of the earthquake. The results of this study can serve as the basis of
      further treatment strategies for the adolescent refugees from major disasters.

PMID- 11831119
TI  - Systemic lupus erythematosus complicated by recurrent spontaneous pneumothorax--a
      case report.
AB  - Despite frequent pleuro-pulmonary involvement, spontaneous pneumothorax is rare
      in patients with systemic lupus erythematosus (SLE). Here, we report a 17-year
      old female patient with SLE, complicated by multiple organs involvement. She
      initially presented with interstitial pneumonitis and pulmonary hemorrhage,
      followed by spontaneous pneumothorax and CNS involvement. The patient was treated
      with immunosuppressive agents, including steroid and cyclophosphamide pulse
      therapies. Spontaneous pneumothorax happened to her once again at a different
      location during treatment. After aggressive therapy, the disease activity of SLE
      gradually diminished, and pneumothorax had not recurred during the further follow
      up. Therefore, the pneumothorax may occur in SLE patients with high disease
      activity.

PMID- 11831120
TI  - Spontaneous femoral neck fracture complicating a healed subtrochanteric fracture-
      a case report.
AB  - A rare case of spontaneous femoral neck fracture complicating a healed
      subtrochanteric fracture was encountered in an 85-year-old female. The
      subtrochanteric fracture was caused by a minor trauma with no other combined
      injury. Patient received close reduction and internal fixation two days later and
      the fracture healed in three months. Six months after operation, spontaneous
      ispilateral femoral neck fracture occurred without trauma. Although there were
      some reports about subcapital fracture or femur neck fracture complication after
      operation, this is the first case of spontaneous femoral neck fracture after
      healed subtrochanteric fracture which was treated with a 95 degrees dynamic
      condylar screw (DCS) and side plate previously without technical error.

PMID- 11831121
TI  - [Overuse injury syndromes of the locomotor system].
AB  - Related either to athletic activities and recreation or to various professional
      activities, overuse injuries of the musculoskeletal system are common in the life
      of modern humans. Various studies indicate that approximately 30% to 50% of all
      sports injuries are caused by overuse. Therefore, it is not surprising that
      overuse injuries are frequently discussed. The mode of this discussion is usually
      limited to the analysis of different individual painful syndromes, specific
      localization of the painful syndrome in the musculoskeletal system, or the
      specific tissues affected by overuse injuries (tendinitis, bursitis, stress
      fractures, etc.). The purpose of this article is to systematically present
      today's knowledge of overuse injuries which affect the musculoskeletal system as
      a whole. Regardless of the localisation and the affected tissue, all clinical
      entities are presented in the same manner: the name and the definition of the
      syndrome, aetiopathogenesis, clinical picture, diagnostic, non operative, and
      surgical treatment, and the possibility of prevention. Beside presenting the
      newest discoveries reported in medical literature, this article also brings a
      wealth of individual cases and experiences encompassing histopathological
      examination, x-ray analysis, and the results of both conservative and surgical
      procedures.

PMID- 11831123
TI  - [Overuse injury syndromes of the hand, forearm and elbow].
AB  - The basic role of the shoulder, upper arm, elbow, forearm, and wrist is to place
      the hand in the appropriate position, so that it can fulfill its function. The
      upper extremity, especially the wrist and the hand, has a very complex anatomy
      with a large number of bones, muscles, tendons and nerves. They are essential to
      work and sport activities and are subject to acute and/or chronic mechanical
      injuries. This is why overuse injuries are the most common in these regions. They
      are often characterised by tendinitis, tenosynovitis, tunnel syndromes, or stress
      fractures. This paper gives an overview of the most common overuse syndromes of
      the hand, wrist, forearm and elbow, describing their characteristic symptoms and
      methods of diagnosis and treatment. The syndromes are trigger finger, dorsal
      radiocarpal impingement syndrome (gymnast's wrist), DeQuervain's disease,
      tenosynovitis of other dorsal compartments, intersection syndrome (oarsman's
      wrist), flexor carpi ulnaris tendinitis, flexor carpi radialis tendonitis,
      humeral epicondylitis (tennis elbow), posterior impingement syndrome of the
      elbow, medial tension and lateral compression syndrome, stress fracture in the
      hand, wrist, forearm and elbow, and tunnel syndromes.

PMID- 11831122
TI  - [Overuse injury syndromes in the shoulder area].
AB  - The shoulder is the most movable and the most unstable joint in a human body. The
      glenohumeral joint is particularly vulnerable because overhead activities put
      tremendous stress on its static stabilizers (ligamentous labral complex) and the
      dynamic stabilizers (rotator cuff muscles). Overhead activities may stretch or
      injure the static stabilizers. Minor aberrations in mechanisms controlling
      stability have a significant and cumulative effect on the shoulder biomechanics,
      and increase the risk of injury. Impingement syndrome and glenohumeral
      instability are predominant injuries affecting the shoulder.

PMID- 11831125
TI  - [The groin pain syndrome].
AB  - Groin pain is defined as tendon enthesitis of adductor longus muscle and/or
      abdominal muscles that may lead to degenerative arthropathy of pubic symphises in
      an advanced stage. Pubic region is a point where kinematic forces cross. The
      balance between the adductor and abdominal muscles is of great importance, as
      well as the elasticity of pubic symphises which enables movement of up to 2 mm
      and rotation of up to 3 degrees. The weakness of the abdominal muscle wall, known
      as the sportsman's hernia, is the most common cause of painful groin. Groin pain
      is the most common in soccer players (6.24% in Croatia). Most authors believe
      that the main cause of groin pain is the adductor muscle overload. When active,
      sportsmen start to feel a dull pain in the groin region. The adductor test is of
      great importance for physical examination; the patient should be lying supine
      with his hips abducted and flexed at 80 degrees. The test is positive if the
      patient, while attempting to pull his/her legs against pressing in the opposite
      direction, feels a sharp pain in the groins. The treatment of groin pain is
      complex and individual, as its causes may vary from patient to patient. Gradual
      physical therapy combined with pharmacotherapy should be effective in most cases.
      The latter includes nonsteroid anti-inflammatory drugs and muscle relaxants. A
      physical therapy programme usually involves stretching and strengthening of
      adductor muscles, abdominal wall muscles, iliopsoas muscle, quadriceps, and
      hamstrings. In case that physical therapy and pharmacotherapy fail, surgery is
      needed, depending on the cause.

PMID- 11831124
TI  - [The most common overuse injury syndromes of the upper extremity associated with
      work activity].
AB  - Repetitive use of upper extremities, non-physiological body posture, especially
      of cervical spine, shoulders, lower arms, and fists are still present in modern
      technological processes. Innate deformities, weakness of connective tissue,
      accompanying morbidity (radicular symptoms, neuropathies, superior thoracic
      aperture syndrome, vasopathies and neuroses) are significant pathogenic overuse
      syndromes. Other causes of overuse syndromes are non-ergonomic tools, musical
      instruments, furniture, or keyboards. Lack of training for jobs involving
      repetitive movements, as well as job dissatisfaction are additional aggravating
      factors of the overuse syndrome. Polypragmasy with drug and physical therapy,
      insufficient rehabilitation, and questionable medical prognosis of working
      capacity are challenges to public health of even in richer societies. This paper
      describes the most common overuse syndromes of upper extremities. The aetiology
      of reflex dystrophy syndrome, carpal tunnel, and myofascial painful syndrome are
      still insufficiently explained. The paper also presents data collected in a group
      of 40 metal workers exposed to significant shoulder strain. They more often
      reported pain in the cervical spine than the control group of workers under
      moderate strain (45% v. 7.5%; P < 0.01), as well as pain in the shoulders (12.5%
      v. 5.0%) and stiffened hand (22.5%:7.5%). Symptoms were significantly more
      frequent in the dominant hand. A common diagnosis in a sample of 110 musicians
      was a change in the shoulder joint, which was more distinct in the right shoulder
      (10%) than in the left (7%) and comparable in the elbows (8%). The paper proceeds
      with cases of advanced overuse syndrome in a textile worker and cases of
      dissimulation in a physician and a guitarist. The paper stresses the importance
      of quantification of morphological and functional changes in overuse syndromes
      and discusses the necessity of prevention, education, early diagnosis,
      pharmacological and physical therapy, and rehabilitation of overuse syndromes.

PMID- 11831126
TI  - [Overuse injury syndromes of the knee].
AB  - Overuse injuries are frequent in the knee joint. The reason for this is that the
      knee joint is engaged in all sports activities. Furthermore, the joint area has
      numerous attachment points for muscles and tendons and numerous bursae. Another
      reason is that the specific joint between the patella and femur (patellofemoral
      joint) constitutes a part of the knee joint. Speaking in general terms, all
      overuse injuries in the knee joint can be divided in four groups according to the
      aspect: anterior aspect--patellofemoral pain syndrome, patellar tendinitis
      (jumper's knee), Osgood-Schlatter disease, Sinding Larson Johanson disease,
      stress fracture of the patella, fat pad syndrome; medial aspect--plica syndrome,
      semimembranosus tendinitis, pes anserinus tendinitis (bursitis), breaststroker's
      knee, medial retinaculitis; lateral aspect--Iliotibial band friction syndrome
      (runner's knee), Popliteal Tendinitis, Bicipital tendinitis; posterior aspect-
      fabellitis, medial gastrocnemius strain. There are numerous possible reasons for
      pain caused by overuse injuries around the knee joint, but two are the most
      frequent: patellar tendinitis (jumper's knee) and Iliotibial band friction
      syndrome (runner's knee). This paper gives a brief overview of overuse injuries
      of the knee joint including their definition, anatomy, aetiology, clinical
      symptoms and signs, and non-operative and surgical treatment.

PMID- 11831127
TI  - [Anterior knee pain associated with sports and work].
AB  - Anterior knee pain is not a disease, but a syndrome with numerous causes. This
      paper describes its appearance in the patellofemoral joint in sportsmen and in
      untrained people. Chondromalacia patellae is a condition of the cartilage, not a
      disease, that is, it is never diagnosed alone. Relative muscular insufficiency,
      especially of the knee extensors, may occur in children and adolescents, as they
      grow rapidly. The consequence is a unbalance of active stabilizers and the
      disturbance of the slippery trail of patella, particularly in the presence of
      dysplasia of patellofemoral joint. The impingement syndrome pain occurs in
      sportsmen and people overloading the patellofemoral joint. Other causes of
      anterior knee pain should be excluded in clinical examination and slippery trail
      of patella, its position, and signs of instability should be determined. This
      paper gives an overview of patellar chondromalacia, lateral pressure syndrome,
      patellar subluxation, patellar acute and recurrent luxation, and idiopathic
      anterior knee pain. The treatment is basically conservative. Stretching exercises
      and the strengthening of certain groups of femoral muscles serves to regain the
      balance, thus normalising the slippery trail and taking off the burden from the
      patellofemoral joint. If conservative treatment fails, surgery is the
      alternative.

PMID- 11831128
TI  - [Overuse injury syndromes of the calf and foot] ].
AB  - The lower leg, foot and ankle form a functional unit of the locomotor system with
      an important static and dynamic function. Injury or loss of function of any
      muscle group of the lower leg and the foot influences normal gait or impedes
      standing. Increased or frequent loads on the muscle group may lead to pain
      syndromes known as overuse syndromes or overuse injuries. Athletes and certain
      professions involving standing or walking for a long time are especially
      susceptible to increased muscle strains. This article describes and clarifies the
      causes and the development of the pain syndromes in the lower leg, foot and ankle
      associated with certain professions or sports. The description of anatomical
      relationships and functions of individual muscle groups is here to clarify the
      occurrence of overuse injuries which may involve the muscle itself, the tendon,
      or the point of their attachment to the bone. The article describes observations
      and experiences from everyday clinical practice, but it also summarises results
      described in recent publications. The focus is also put on the therapy, which is
      usually conservative. Particular mention is given to new non-invasive surgical
      techniques. The article describes the most common overuse injuries of the lower
      leg such as shin splints, tibialis posterior syndrome, chronic anterior
      compartment syndrome, overuse injury of the Achilles tendon, enthesitis of the
      tendo Achilles, retrocalcanear bursitis and rupture of the Achilles tendon. In
      the foot area the most frequent overuse syndromes are the plantar fasciitis,
      tibialis posterior tendinitis, tendinitis of the long flexor of the toe, toe
      extensor tendinitis, and also anterior and posterior impingement syndromes of the
      ankle.

PMID- 11831129
TI  - [Occupational overuse injury syndromes of the lower extremities] ].
AB  - The aim of this study was to determine the frequency and significance of
      overstretching of the lower limbs in working population. Occupational
      etiopathogenic factors are often similar to those in sports and involve frequent
      repetition of single movements which cause microtraumas to the
      bone/joint/muscular system including the lower limbs. The resulting pain is
      described as the overuse syndrome. Literature reports significantly less data on
      working population than on athletes. This retrospective epidemiological study
      investigated two groups of patients. The first group consisted of 120 workers who
      had been on sick leave for a longer time and underwent disability review within
      the period of one year. The second group consisted of 86 patients in general
      practice who were on sick leave in one month. One third of the patients on sick
      leave were found one or more diseases of bone/joint/muscular system. Of patients
      with the overuse syndrome two were found in the first group, and two in the
      second. In both groups, the overuse syndrome came fourth in incidence. The
      results are lower than expected, particularly in athletes. The paper discusses
      possible reasons for these results, such as test sensitivity and criteria.

PMID- 11831130
TI  - [Stress fractures].
AB  - Stress fractures are common overuse injuries, ranging between 1.1% and 3.7% of
      all athletic injuries. Causes are many and usually involve repetitive submaximal
      stress. There is a wide research evidence showing that training errors cause
      stress fractures in as many as 22% to 75% of cases. Intrinsic factors such as
      hormonal imbalance may also contribute to the onset of stress fractures,
      especially in women. During medical examination, it is essential always to bear
      in mind the possibility of stress fracture. Clinical diagnosis is therefore the
      basic procedure, followed by other diagnostic methods in the following order:
      radiology, scintigraphy, and MRI. Most stress fractures are uncomplicated and can
      be managed through rest and restriction from precipitating activities for 4-6
      weeks. A subset of stress fractures can present a high risk for progression to
      complete fracture, delayed union, or nonunion. Specific sites for this type of
      stress fracture are the femoral neck, the anterior cortex of the tibia, the
      tarsal navicular, the fifth metatarsal (Jones fracture), and the great toe
      sesamoids. Therefore, high-risk stress fractures require aggressive treatment,
      and in some cases even surgical intervention is appropriate.

PMID- 11831131
TI  - [Overuse injury syndromes in children and adolescents].
AB  - More and more children participate in sports competitions. The main difference
      between children and adults is that the former still grow and develop. An
      immature musculoskeletal system is less able to cope with repetitive
      biomechanical stress. Sites of overuse injury are the sites of rapid growth:
      epiphysis, apophysis, and growth plates. Overuse injuries in children most
      commonly affect the cartilage where it meets with the tendons (nonarticular
      chondrosis), cartilage and bone at the joints surfaces (primary and secondary
      osteochondrosis), or the bone and its physis (stress fractures). The most
      characteristic overuse injuries in children are physeal stress fracture and
      osteochondrosis. The basic diagnostic and treatment principles in children
      greatly correspond to those in adults. The prevention of overuse injuries in
      children is very important. To minimise the injuries, children should be
      encouraged to limit the length of exercise, use high-quality equipment properly,
      cross train, and participate in conditioning programs to develop strength and
      flexibility.

PMID- 11831132
TI  - [Physical procedures in the treatment of overuse injury syndromes of the
      locomotor system].
AB  - As a rule, the treatment of the overuse syndrome in the locomotor's system is non
      surgical, and surgical treatment is needed on rare occasions. Non-surgical
      treatment should start as soon as possible. The first step is to half or modify
      sports activities. The treatment includes administration of non-steroidal anti
      inflammatory drugs, physical therapy, stretching exercises, and the strengthening
      of affected muscles. The programme should be adapted to the patient, taking into
      account the localization and the degree of the injury, as well as his/her sport
      or work-related activities. The RICE therapeutic programme is important in the
      treatment of overuse syndromes, especially within the first 72 hours from the
      occurrence of first symptoms, as it shortens the duration of convalescence for as
      much as 50%-70%. Beside stabilisation of the joint with optimal loading of
      antagonistic muscles, stretching exercises have the leading position in
      prevention and treatment of overuse injuries. During rehabilitation, it is
      necessary to change activity, its duration and intensity. When a person
      successfully resumes its sports activities with full load, the rehabilitation is
      considered completed. No surgical or non-surgical method can warrant a hundred
      percent recovery for any localization of overuse injury. Prevention, education,
      and close co-operation between the physician, athlete, and the coach is therefore
      crucial and is receiving increasing attention.

PMID- 11831133
TI  - [Isokinetic diagnosis: rehabilitation in overuse injury syndromes].
AB  - Isokinetic testing of the musculoskeletal system is an important diagnostic
      method in the course of rehabilitation because it is adapted to individual and
      objective in measuring biomechanical parameters. Isokinetic dynamometer serves as
      a measurement and/or exercising device and helps user to achieve maximum force in
      through a range of motion, accommodating for potential pain or fatigue.
      Isokinetic dynamometer measures strength, torque, and generated power as well as
      the range of motion of the joint and distribution of strength in the range of
      motion. These results, as well as the relation between agonists and antagonists,
      acceleration time, velocity of motion reciprocity, maximum torque angle, and the
      fatigue/endurance index are computed and compared with standard values using
      software. Repeated testing shows changes in parameters in later stages, ensuring
      an accurate insight in the progress of rehabilitation. This paper describes the
      treatment of a 14-year-old boy engaged in rowing who suffered from suprapatellar
      pain and instability of the knee. After isokinetic testing and rehabilitation the
      boy resumed his sport activities.

PMID- 11831134
TI  - [Evaluation of work capacity and/or disability in patients with overuse injury
      syndromes of the locomotor system].
AB  - Clinical picture and subject's occupation are the main points of reference in the
      evaluation of work capacity in subjects with overuse syndrome. Particular
      attention is paid to the degree and the location of pain, as well as functional
      limitations with respect to demands of the workplace. If the diagnosis is right
      and therapy and rehabilitation intensive, overuse syndrome usually does not
      entail long sick leaves. Exceptions are the athletes and certain jobs which
      require longer periods of rehabilitation. Furthermore, untimely diagnosis and
      inadequate treatment may extend the period of incapacity. If the therapy and
      medical rehabilitation cannot completely remedy the functional deficit in
      performing the regular job, application of pension policy regulations may be
      necessary. This applies to the immediate danger of disability with the
      possibility to change the job for a more adequate one, as well as to the
      disability due to occupational or general incapacity to work. If the health
      condition predisposes younger persons to disability, they may exercise their
      right to professional rehabilitation. This review gives a list of occupational
      diseases and causes which may be applied to the disability generated by the
      overuse syndrome.

PMID- 11831135
TI  - Communal bereavement and the incidence of very low birthweight in Sweden.
AB  - Prime minister Olof Palme's murder in 1986 and the sinking of the ferry Estonia
      in 1994 were stressful events for many Swedes, but did that stress affect health?
      We used an interrupted time-series design to measure the association between
      these events and the incidence of very low birthweight. Effects of male
      unemployment, size of the birth cohort, and temperature were controlled in our
      analysis of data for the period 1973-1995. The incidence of very low birthweight
      rose significantly in the months following the Palme murder and the Estonia
      catastrophe. Events that trigger communal bereavement at the scale we study may
      seem rare but they do occur (e.g., destruction of the World Trade Center and
      attack on the Pentagon). Events with less visibility, moreover, may induce
      communal bereavement in smaller populations defined by geography or
      organizational participation.

PMID- 11831136
TI  - Evidence-based medicine, clinical uncertainty, and learning to doctor.
AB  - For the past two decades, evidence-based medicine (EBM), or the reliance on
      current scientific evidence to reach medical decisions, has been embraced as a
      new paradigm to standardize clinical care. Drawing from in-depth interviews with
      seventeen pediatric residents in two residency programs, we evaluate the extent
      to which the medical sociology scholarship on uncertainty analytically elucidates
      the recent influx of EBM during residency training. Our findings suggest that
      residents interpret EBM in varying ways to match their work practices:
      "Librarians" consult the literature while "researchers" evaluate it critically.
      For both groups, EBM might generate new uncertainties due to the increased
      reliance on information technologies and epidemiology. Whether EBM reduces
      uncertainty depends upon the residents' understanding of standardized knowledge
      and consequent incorporation of EBM in their clinical practice. Contrary to the
      predictions of some sociologists, EBM does not lead to a diminishment of
      humanitarian values in medical care. Nor does EBM lead to a science-based
      meritocracy on the patient ward, as claimed by some EBM advocates. Our conceptual
      updating of uncertainty emphasizes the continuous management of uncertainty
      during the medical socialization process. We argue that managing uncertainty
      develops along with what we term evidence-based clinical judgment.

PMID- 11831137
TI  - Social distance and patients' rating of healthcare providers.
AB  - Racial inequity in the provision of healthcare is widely recognized. In this
      paper, I assess the role of social distance from healthcare providers in
      accounting for whites' higher rating of healthcare providers. Using data from the
      Detroit Area Study, I test whether having higher socioeconomic status, like most
      healthcare providers, and racial concordance with healthcare provider account for
      the gap in satisfaction between whites and African Americans. I find that
      socioeconomic status and racial concordance variables account for a portion of
      whites' higher rating of the respect shown by their healthcare provider. Racial
      differences in evaluation of time spent with healthcare provider are accounted
      for by socioeconomic status, but not racial concordance. As researchers explore
      the causes of and remedies for the racial disparity in use and evaluation of
      healthcare, the subtle and indirect effects of race on the patient-healthcare
      provider relationship must be considered.

PMID- 11831138
TI  - The effects of income inequality and income level on mortality vary by population
      size in Texas counties.
AB  - OBJECTIVES: This study uses the counties of Texas to empirically test the
      predictions of Wilkinson's theory on the role of income and inequality in
      explaining health differentials in populations. Wilkinson predicts (1) that
      health is affected more by income inequality than average income in areas with
      large population, and (2) that health is affected more by average income than
      income inequality in areas with small population. We investigate how large the
      population of a unit must be for income inequality within the unit to affect
      mortality. METHODS: Measures of income inequality were computed from the 1990
      U.S. census data and mortality was computed from Vital Statistics data. Poisson
      regressions estimated the age-adjusted relative risk of the top quintile relative
      to the bottom quintile for equality and for income among selections of Texas
      counties based on population size. County ethnic composition, educational level,
      and health care access were controlled for. RESULTS: Among counties with
      populations greater than 150,000, the risk of death was lower in counties with
      more equal income distribution than in counties with less equal income
      distribution. Among counties with population less than 150,000, median income
      affected relative risk in counties with less than 30 percent Hispanics, but not
      in those with more than 30 percent Hispanics. CONCLUSIONS: This study provides
      some support for the predictions of Wilkinson's theory.

PMID- 11831139
TI  - Cigarette diffusion and sex differences in smoking.
AB  - Because the recent narrowing of the sex differential in smoking (and mortality
      from smoking-related causes) coincides with movement toward gender equality and
      independence among women, it suggests that rising status among women has
      contributed to their adoption of male smoking behavior (and ultimately to
      worsening longevity). However, an alternative "cigarette diffusion" explanation
      suggests that convergence in male and female smoking is the byproduct of a female
      lag in the process of cigarette adoption, diffusion, and abatement. Using
      multilevel models and data for 16 European nations from 1988-1995, the analysis
      demonstrates consistent support for the predictions of the cigarette diffusion
      explanation. Smoking of men and women becomes more similar in nations that have
      the longest history of cigarette use rather than the greatest gender equality.

PMID- 11831140
TI  - Perceived discrimination and early substance abuse among American Indian
      children.
AB  - This study investigated internalizing and externalizing symptoms as potential
      mediators of the relationship between perceived discrimination and early
      substance abuse among 195 American Indian 5 through 8 graders from three
      reservations that share a common culture (e.g., language, spiritual beliefs, and
      traditional practices) in the upper Midwest. The findings indicated that,
      although perceived discrimination contributed significantly to internalizing
      symptoms among the adolescents, internalizing symptoms were unrelated to early
      substance abuse. Rather, the effects of perceived discrimination on early
      substance abuse were mediated by adolescent anger and delinquent behaviors. The
      results are discussed in terms of the consequences of perceived discrimination on
      the development of American Indian early adolescents.

PMID- 11831141
TI  - Part-time work and hurried adolescence: the links among work intensity, social
      activities, health behaviors, and substance use.
AB  - The present study examines adolescents' part-time work intensity and its relation
      to participation in various activities as well as substance use. We consider
      mechanisms articulated in two theoretical perspectives on how high work intensity
      is associated with substance use: (1) the "time trade-off perspective," and (2)
      "the precocious development perspective." Nationally representative data were
      drawn from the "Monitoring the Future" project from 8th, 10th and 12th grade
      students (overall N approximately 380,000) to address our research questions.
      Work intensity was found to be linked to more time spent on unstructured social
      activities, but to less time spent engaged in sports, health behaviors, and
      school-related activities. Social time use and health behaviors were found to
      partially mediate the relationship between work hours and substance use. Overall,
      results provide evidence for a combination of both perspectives.

PMID- 11831144
TI  - Primary care in eastern North Carolina. Past, present, and challenging future.

PMID- 11831143
TI  - Demography and health care in eastern North Carolina.

PMID- 11831142
TI  - Birth weight and income: interactions across generations.
AB  - This paper attempts to answer a series of questions regarding the interaction of
      income and birth weight across generations. First, does the effect of the income
      of a mother during her pregnancy on her infant's birth weight depend on the
      family's birth weight history (genetic predisposition)? Second, does the effect
      of low birth weight status on adult life chances depend on income during early
      childhood? These questions have implications for the way we envision the
      biological and social worlds as interacting across generations. To address these
      issues, this study uses intergenerational data from the Panel Study of Income
      Dynamics, survey years 1968 through 1992. Results of sibling comparisons (family
      fixed-effects models) demonstrate that maternal income has a significant impact
      on birth weight for those infants who are already at high risk hereditarily
      (i.e., who have a low birth weight parent). However, it is not clear whether
      income acts as a developmental buffer for low birth weight infants as their lives
      progress. These findings suggest the existence of biosocial interactions between
      hereditary predisposition and socio-economic environment.

PMID- 11831145
TI  - Surgical services in eastern North Carolina. A story of continuing evolution.

PMID- 11831147
TI  - Cardiology in eastern North Carolina, 1960-2001.

PMID- 11831146
TI  - Pediatric health care in eastern North Carolina, 1976-2001.

PMID- 11831148
TI  - Cancer care in eastern North Carolina, 1975-2000.

PMID- 11831149
TI  - Hospital care in eastern North Carolina. Responsiveness, flexibility, and bottom
      line finances keep rural centers vital.

PMID- 11831150
TI  - [HIV and dentistry. Part 7. The HIV positive dentist or student].
AB  - What should a dentist or dental student do when he happens to be HIV
      seropositive? Should he or she disclose the disease to the patients or, in case
      of a student, to the university? Does he has to give up his practice or perhaps
      not even open one? Apparently, the legal regulations differ in various parts of
      the world. In the Netherlands dentists are advised to take their own
      responsibility in this matter.

PMID- 11831151
TI  - [Corrections after facial trauma. Experiences with secondary periorbital
      corrections].
AB  - Corrective surgery after primary treatment of periorbital trauma is indicated for
      functional as well as aesthetical reasons. These indications and the over-all
      results will be discussed, based on 56 cases. Surgical techniques such as
      osteotomy of the malar bone or correction of the nose will be presented. It is
      concluded that 60% of the cases achieve a good, final result. In another 30%
      considerable improvements have been realized.

PMID- 11831152
TI  - [Patient views on dental amalgam. An exploratory questionnaire].
AB  - An introductory letter and a precoded questionnaire was sent to a large sample of
      the Dutch population in order to study their views on dental amalgam. Another
      sample was approached by interviewers to study the effect of non-response and a
      third sample was asked to complete a 'neutral' questionnaire so as to preclude
      any influence caused by the phrasing of the introductory letter and the
      questionnaire. It was found that the non-response did affect the results, while
      the phrasing of the letter did not. Based upon the comparison of the samples and
      taking the non-response into account, it is concluded that probably 17% of the
      Dutch population regard amalgam to be potentially harmful. At least 4-5% worry
      about their health because of amalgam fillings and 2-3% attribute existing health
      problems to amalgam. However, none of the respondents of the 'neutral' sample
      spontaneously reports amalgam as a causative factor for illness. The health
      problems mentioned by the respondents are diverse. Headache is mentioned most
      often, followed by fatigue and a metal taste.

PMID- 11831153
TI  - [Female dentists. Style of their professional practice].
AB  - In many Western countries during the past decades there has been a strong
      increase in the number of women dentists. This review on current literature shows
      that women dentists differ from their male colleagues in their way of practising
      the profession. More so than men they prefer to work in a group practice or in
      some kind of partnership. Women dentists also appear to have relatively smaller
      practices than their male colleagues and on average they practise fewer hours per
      week. However, it is important to notice that for women dentists motherhood is an
      important restricting factor with regard to practising their profession, often
      resulting in career break and diminishing professional productivity. Because of
      the strong increase in the percentage of women dentists, it is important for
      future policies to recognise their specific issues and concerns, as well as the
      consequences for dentistry of their way of practising. Thus, planning of manpower
      and infrastructure of dentistry can be done in a more adequate way.

PMID- 11831154
TI  - [Malocclusions and craniomandibular dysfunction. A review].

PMID- 11831155
TI  - [Osteomyelitis after removal of impacted third molars].

PMID- 11831156
TI  - [HIV and dentistry. Part 8. Can a dentist refuse treatment to an HIV seropositive
      patient?].
AB  - An overview is presented of the ethical guidelines in different parts of the
      world on the subject of dental treatment of HIV-seropositive patients. Does a
      dentist ever have the right to decline treatment and will the answer to this
      question be influenced by the presence or absence of dental complaints? Based on
      several reports it is likely that some dentists refuse treatment of HIV
      seropositive patients.

PMID- 11831157
TI  - [Amalgam. XVII. Associations between views on dental amalgam and other
      variables].
AB  - Bivariate associations between views on amalgam in the Netherlands and other
      variables, such as preventive health measures and environmental ones, information
      on amalgam in the mass media, knowledge of the composition of amalgam, socio
      demographic variables, visits to alternative healers, regularity of dental
      attendance, number of teeth, etcetera, appear in general to be low, yet
      significant, and even very low.

PMID- 11831158
TI  - [The transmandibular implant. From bone loss to bone growth--an investigation of
      116 patients].
AB  - In a prospective study 116 consecutive patients were treated according to a
      revised protocol to induce and control bone growth. Revisions included: 1.
      lengthening of the transosseous posts and cortical screws between the mental
      foramina so that two threads extended beyond the alveolar crest of the mandible
      without protruding through the mucosa; and 2. fabricating an implant borne
      prosthesis with a gap of 2 mm between the denture base and the mucosal tissues in
      the saddle areas and loading only the retromolar pads. The gap was re-opened
      every 8 weeks until further bone growth would prevent proper oral hygiene.
      Measurements of the height of the mandible were made using a digital millimeter
      caliper and standardized radiographs. The radiographic enlargement was calculated
      per radiograph for the sites to be measured. The follow-up varied from 15 up to
      39 months. Bone growth had occurred in 104 of the 116 patients, while the
      resorption of bone had ceased in the remaining patients. The increase of bone
      height varied from 9 mm in patients with severe mandibular atrophy down to 2 mm
      for patients with mild atrophy. The revised protocol for TMI insertion and
      rehabilitation is advocated to promote bone growth and to cease further
      resorption in the atrophic mandible.

PMID- 11831159
TI  - [Can jaws grow? Comment on 'The transmandibular implant. From bone loss to bone
      growth'].

PMID- 11831160
TI  - [Sarcoidosis, a disease with many facets].
AB  - Sarcoidosis is a multisystem granulomatous disorder of unknown aetiology, most
      commonly affecting young adults. The course and the prognosis may correlate with
      the mode of onset. An acute onset with erythema nodosum heralds a self-limiting
      course and spontaneous resolution, whereas an insidious onset may be followed by
      relentless, progressive fibrosis.

PMID- 11831161
TI  - [A local swelling of the bottom lip].

PMID- 11831162
TI  - [Dental education in the Netherlands through the years].
AB  - Official dental education in the Netherlands started some 120 years ago, in 1876.
      From that moment on dental education developed itself from an old-fashioned
      apprentice system into the modern well-structured university education of today.

PMID- 11831163
TI  - [Dental education: a new approach].
AB  - A new curriculum will be introduced in the Academic Centre for Dentistry
      Amsterdam (ACTA) in September 1994. Besides adaption of the contents of the
      curriculum, a new philosophy in teaching will be adopted. In this article the
      educational principles and conditions are discussed which have to result in
      modern student centered teaching. In addition, a concrete illustration is given
      of the effects this will have on the ACTA curriculum.

PMID- 11831164
TI  - [Academic education of dentists].
AB  - The aims of an academic education are phrased on the basis of a report of the
      Rectors of Dutch Universities, published in 1993. These aims are explicited in
      more detail for academic dental education. In this respect notable educational
      forms used in the dental schools in the Netherlands and Flanders (Belgium) are
      mentioned. A minimum-curriculum for academic education in dentistry is
      formulated, including theoretical courses, application courses and methods of
      reinforcement in all parts of the entire dental curriculum.

PMID- 11831165
TI  - [Review of dental study programs: purpose and procedure].
AB  - The Dutch universities jointly developed a review system in order to assess all
      study programmes within a period of 5 to 6 years. The dental studies were
      reviewed in 1993. This review system is based on internal quality assessment. For
      this assessment four aspects are important: conditions, the teaching process, the
      characteristics of the final product (the dentist) and the course of the
      evaluation of the study programme. The external quality assessment consists of
      the writing of a self-study, with a survey of strong and weak points and an own
      judgement of the dental school with respect to the study programme, and a visit
      of the visiting committee. The conclusions of this committee are put down in a
      report which will be published afterwards.

PMID- 11831166
TI  - [The computer in education. Applications in dentistry].
AB  - During the last decade an increased interest in Computer Managed Instruction
      (CMI) and Computer Assisted Learning (CAL) can be observed among teachers and
      students in dental education. Both CMI and CAL can be used to manage
      individualized instruction, to assist students in specific scientific tasks and
      to master or enhance knowledge and skills. In balancing the pros and cons against
      each other, it was concluded that CAL should preferably be developed by joint
      efforts of collaborating Dental Colleges. It is expected that new developments in
      authoring systems and hardware will encourage the development of courseware.

PMID- 11831167
TI  - [Dental curriculum in Nijmegen].
AB  - The dental curriculum at the University of Nijmegen is based on what the dentist
      should know and be able to do after his graduation. The programme is divided up
      into cognitive, behavioural and motoric modules. These modules are vertically
      connected through subsequent course years by thematically related lines. For
      every module, the general objectives and general contents have been formulated.
      Moreover, all subcomponents have been specified as instructional objectives. Half
      of the study hours is reserved for practical dentistry, by means of preclinically
      laboratory courses or patient treatment. The curriculum is based on a scientific
      approach of dentistry and emphasis is placed on patient related instructional
      situations.

PMID- 11831168
TI  - [Communication and dental practice. Practica in social dentistry and
      information].
AB  - An overview is presented of several undergraduate courses given by the Department
      of Social Dentistry and Dental Health Education (ACTA). A short description of
      the contents of courses in communication skills, treatment of anxious patients
      and practice management is given together with the results of a student
      evaluation. Students consider these courses useful and relevant for future dental
      practice. This is especially true in case the direct relevance for clinical
      practice is clear.

PMID- 11831169
TI  - [Dentists' opinion of their education. Results of a survey among dentists who
      graduated from dental school in Nijmegen in the years 1982-1990].
AB  - Five hundred and seventy-eight dental students from the Catholic University of
      Nijmegen (the Netherlands), graduated between 1982 and 1990, were asked by
      questionnaire to give their opinion on their undergraduate dental training. Most
      respondents thought the undergraduate dental education prepared them reasonably
      well for general practice. Yet imperfections in the education were noticed. These
      imperfections show resemblance and slight differences from a similar survey in
      ACTA, the Academic Centre for Dentistry Amsterdam, the Netherlands.

PMID- 11831170
TI  - [The Dutch Dental Association's vision of dental training].
AB  - The Dutch Dental Association (NMT) feels very involved in dental schooling and
      advocates as broad an education as possible with explicit attention to the
      'gatekeeper' function of the dentist in general practice, diagnostics and the
      development of motor skills for complex, restorative treatments. Attention is
      demanded to place individual professional practice in a wider context of dental
      staff and a network of opportunities of referral. The NMT wishes to develop a
      system for the profession in which guidelines, intercollegial testing and
      effective accredited provision of further training, systemic opportunities and
      guidelines for the promotion of expertise are given in the areas of technical
      methods, organisation of practices and professional attitude. They wish to
      support the newly-qualified dentist through the introduction of a year of
      practical training linked to study, so that an 'educational continuum' of
      education, training and continual further training develops, and to make a
      contribution not just organizationally, but also regarding the content of the
      curriculum, certainly where it concerns the sociological aspects and the needs of
      the professional group.

PMID- 11831171
TI  - [Education visitation. The visitation report of dental study programs].

PMID- 11831172
TI  - [The education continuum in dentistry].

PMID- 11831173
TI  - [Guidelines on occlusion and articulation. Part 1. Overdentures on implants in
      the edentulous lower jaw].
AB  - When loading dental implants it is generally accepted that one should minimize
      horizontal forces. This has its implications for the choice of the occlusal
      concept that is to be used for overdentures on implants. In this article various
      occlusal concepts for overdentures on dental implants in the lower jaw opposing
      different types of dental arch mutilation in the upper jaw are discussed. Apart
      from number, length and position of the implants, the condition of the opposite
      dental arch and the intermaxillary relationship play a role when choosing an
      occlusal concept. This article discusses the type of overdenture and the occlusal
      concepts for the edentulous lower jaw. A distinction is made between mucosally
      borne, mucosally-implant borne and implant borne overdentures on dental implants.

PMID- 11831174
TI  - [HIV and dentistry. Part 9. HIV infection and dental care].
AB  - Dental treatment of HIV-infected or AIDS patients can be safely performed in the
      dental office. In general, no special precautions are necessary. Only in case of
      severe illness a dental emergency may have to be referred to a dedicated clinic.
      Ideally, the dentist should have the possibility to treat his own patient in such
      a clinic.

PMID- 11831175
TI  - [The condition of crowding and spacing. Measuring or estimation?].
AB  - Two methods for the assessment of the amount of crowding or spacing (measuring
      and assessment by eye) are compared. Both methods are well comparable and
      reproducible. Assessment by eye has the practical advantage that it takes
      considerable less time.

PMID- 11831177
TI  - [Second primary tumors following treatment of squamous cell carcinoma of the oral
      cavity].
AB  - In the hospital of the Free University in Amsterdam (the Netherlands) 727
      patients with primary squamous cell carcinoma of the oral cavity and lip have
      been studied for the incidence of second primary tumors occurring in the
      respiratory and upper digestive tract. Out of the 727 patients, 74 (10.2%)
      developed a second primary tumor in these tracts. The incidence of second primary
      tumors was expressed per 1.000 person-years of follow-up; 28 second primary
      tumors per 1.000 person-years of follow-up were seen in the respiratory and upper
      digestive tract. The patients ran the risk of developing a second primary tumor
      at a steady rate of approximately 2.8% per year during at least ten years.
      Furthermore, an increasing incidence of second primary tumors could be observed
      in case of increasing use of tobacco.

PMID- 11831178
TI  - [Dental referral of drug addicts].
AB  - Reasons for drug addicts' non-compliance to dental referral were investigated.
      Sixty-eight out of 83 addicts referred to the dentist were interviewed. Eighty
      one percent intended to go, but only 42% did show up for their first appointment.
      Mean dental anxiety score (SDAI) was 23.6. An active referral of a non-anxious
      patient who visited the dentist in the past if in pain appeared least likely to
      fail. Dental care as an integral part of care for drug addicts is advocated.

PMID- 11831176
TI  - [Amalgam. XVIII. Group characteristics in the attitude to and perception of
      amalgam].
AB  - Based upon their answers to a questionnaire, 1147 respondents could be divided
      into four groups. One group has a critical attitude to amalgam, the second is
      'uncritical', the third 'uninformed' and the fourth, among which many with health
      complaints attributed to amalgam fillings, is named 'imaginary group'. The
      division is based upon nine out of 15 variables: 1. potential harmfulness of
      amalgam; 2. worry about the general health because of amalgam; 3. attribution of
      existing health complaints to amalgam; 4. reading/hearing about harmfulness of
      amalgam; 5. visits to alternative healers and quacks; 6. knowing that fish
      contains mercury; 7. knowing that amalgam contains mercury; 8. opinions on
      homeopathic medicines; 9. presence of dental amalgam. Among others preventive
      health and environmental actions were not of importance. The respondents,
      distinguished by sex, age and education, are not evenly distributed. An analysis
      of a second sample is considered in general to corroborate the findings. Although
      the analysis cannot reveal causal relationships, the results suggest the
      possibility that the population is kidded into distrust towards amalgam by the
      mass media and alternative healers.

PMID- 11831179
TI  - [An unusual periapical radiolucency].

PMID- 11831180
TI  - [Porcelain onlays].
AB  - This article covers the clinical application of feldspathic porcelain onlays. The
      indication, tooth preparation, try-in and cementation procedures using total
      etching and the latest concepts in dentin bonding are discussed. When properly
      executed fired porcelain onlays can meet the highest esthetic demands but they
      require maximum skills, both of the dental surgeon and of the dental technician.

PMID- 11831181
TI  - [Caries prevalence among schoolchildren in Zoetermeer. A study performed by
      primary health doctors].
AB  - In a study performed by primary health doctors among 10- and 11-year-olds in
      Zoetermeer (the Netherlands), 72% of the children were found to possess four
      healthy permanent first molars. The examination was exclusively based on visual
      inspection by means of mouth mirrors.

PMID- 11831182
TI  - [Symptomatic bacteremia after periodontal treatment].
AB  - Symptomatic bacteremia after dental treatment in an apparently healthy patient is
      an indication for preventive antibiotic treatment. This article describes the
      case of a patient with clinical symptoms of bacteremia after periodontal
      treatment, in whom the blood cultures remained positive after oral administration
      of amoxicillin (Chlamoxyl). Intramuscular administration of penicillin
      (Bicilline) was able to prevent the clinical symptoms as well as the bacteremia.

PMID- 11831183
TI  - [Special dentistry assistance. An evaluation of the revised ruling 1990].
AB  - Public Health insurance provision of dental care for patients with a physical,
      mental, dental or medical handicap has been reorganized in 1990. In order to
      evaluate this reorganization, general dental practitioners, dentists in hospital
      clinics or institutions for the handicapped as well as dentists employed as
      advisors to local health insurance authorities were interviewed. Results show
      that, until now, the reorganization has not resulted in an increase of seeking
      dental care by handicapped patients at the general dental practitioner's. The
      reorganization seems to have taken place in too much haste, thus not leading to
      the desired provision of dental care for handicapped patients.

PMID- 11831184
TI  - [An unexplained swelling in the upper jaw].

PMID- 11831185
TI  - [Where does BSE in the Netherlands come from?].
AB  - It is only in the last 5 years that the Netherlands has been confronted with
      cases of bovine spongiform encephalopathy (BSE). The cases diagnosed to date have
      not been clearly linked to imports from the United Kingdom. This article
      describes the various possible explanations for the Dutch cases. The risk factors
      involved, have either a connection with imported BSE, local origin of BSE, or
      both. These factors can also be divided into introductory risk and propagation
      risk, terms that were also used in an EU risk assessment study. Research at ID
      Lelystad since the early 1990s and at IKC-Ede has tried to assess the relative
      importance of the various risk factors, the results of which are discussed in
      this paper. The paper does not deal with the specifics of the cases diagnosed to
      date, because of the absence of an in-depth epidemiological investigation, but
      provides a general assessment of the risk factors that might have played a role.
      Important factors have been, in addition to the initial imports of cattle and
      meat and bone-meal from the UK, the continuing imports from other countries with
      covert BSE and the cross-contamination within the animal feed production lines.
      Emphasis is on the period of the early and mid-1990s, the period in which most
      calves with diagnosed BSE were born.

PMID- 11831186
TI  - [Clinical gene therapy: genes by prescription?].
AB  - Gene therapy is a medical intervention based on modification of the genetic
      material of living cells. This technique offers widespread possibilities in
      treating or preventing diseases. This applies to genetically determined diseases
      but also to diseases that occur later in life. Cells may be modified ex vivo for
      subsequent administration to patients, or may be altered in vivo by gene therapy
      given directly to the subject. To introduce the genetic material in cells,
      vectors are being used. Currently, most vectors are from viral origin. This
      requires special precautions when producing viral vectors. Gene therapy is
      apparently safe, when the proper indications and contra-indications are taken
      into account. Expectations regarding gene therapy are very high. However, more
      technological barriers are encountered than foreseen and therefore, the clinical
      success up to now is limited.

PMID- 11831187
TI  - [Heart problems in the cat].

PMID- 11831188
TI  - [FIDIN meeting: public relations in an interesting package].

PMID- 11831189
TI  - [ESVD-ECVD Veterinary Dermatology Congress].

PMID- 11831190
TI  - [Drug therapy for the environment?].

PMID- 11831191
TI  - [Heart attack by Mastino's].

PMID- 11831192
TI  - [Mirror. Veterinary medicine in developing countries].

PMID- 11831193
TI  - Seaweed and cancer prevention.

PMID- 11831194
TI  - Evolution of reflux disease management and the role of Nexium. Proceedings of a
      symposium. Porto, Portugal, 7 October 2000.

PMID- 11831195
TI  - Colonic anastomotic stenoses and Memotherm stent fracture: a report of three
      cases.
AB  - Deployment of a Memotherm colonic stent (Bard, Angiomed, Karlsruhe, Germany)
      across anastomotic strictures, following anterior resection, is described in
      three patients. Two patients presented with symptoms of colonic obstruction. Two
      of the patients had previously undergone unsuccessful balloon dilatation of the
      stricture. In the third, in addition to the anastomotic stricture, there was
      local tumor recurrence. Initially, stenting provided effective relief of
      symptoms. However, in all three patients, fracture of the stents occurred at
      intervals of 3-7 months after insertion. This use and complication of colonic
      stenting has not been reported previously.

PMID- 11831196
TI  - Re: Conservative Management of Gradenigo Syndrome in a Child.

PMID- 11831197
TI  - Post-therapy multiply resistant mutant of Pseudomonas aeruginosa.

PMID- 11831198
TI  - Why is there CSF?

PMID- 11831199
TI  - US "boutique medicine" could threaten care for the majority.

PMID- 11831200
TI  - Drug company fined 2.2 million pounds for abusing its dominant position.

PMID- 11831201
TI  - Doctor reprimanded for giving antiretroviral drug to baby who was raped.

PMID- 11831202
TI  - Commentary: virus, host, or environment?

PMID- 11831203
TI  - Commentary: the reality of treating HIV and AIDS in poor countries.

PMID- 11831204
TI  - Commentary: most South Africans cannot afford anti-HIV drugs.

PMID- 11831205
TI  - Commentary: involving traditional birth attendants in prevention of HIV
      transmission needs careful consideration.

PMID- 11831206
TI  - Trends in sex differences in mortality from heart disease: oestrogen may
      contribute to variation in mortality.

PMID- 11831207
TI  - Does the internet harm health? Database of adverse events related to the internet
      has been set up.

PMID- 11831208
TI  - Quinacrine in possible or probable CJD: it is blinded investigators, not
      patients, who must be in equipoise over treatment.

PMID- 11831209
TI  - The twisting force of aged consumers when opening a jar.
AB  - Many people experience difficulty when opening a vacuum-sealed jar. Yet solutions
      to the problem continue to be tool-based rather than exploring the possibility of
      innovative changes in product packaging. Improvement depends on gaining knowledge
      of the capabilities of users, and of using that knowledge as a base for product
      innovation. To establish such a base we took a sample of 750 subjects and asked
      them two questions about how they opened jars at home. We then carried out torque
      measurements using a force transducer shaped like a jam jar. We reached the
      conclusion that if opening torque was reduced to 2 N m then 97.6% of users
      between 50 and 94 years of age and 100% of 20-30 year old users would have no
      difficulty opening a jar.

PMID- 11831210
TI  - A field comparison of neck and shoulder postures in symptomatic and asymptomatic
      office workers.
AB  - Poor neck and shoulder postures have been suggested to be a cause of neck and
      shoulder pain in computer workers. The present study aimed to evaluate and
      compare the head, neck and shoulder postures of office workers with and without
      symptoms in these regions, in their actual work environments. The two all female
      subject groups reported significantly different discomfort scores across five
      trials repeated in a single working day. The results of repeated video capture
      and two-dimensional motion analysis showed that there were trends for increased
      head tilt and neck flexion postures in the symptomatic subjects (n = 8), compared
      to the asymptomatic subjects (n = 8). Symptomatic subjects also tended to have
      more protracted acromions compared with asymptomatic subjects and showed greater
      movement excursions in the head segment and the acromion. All subjects
      demonstrated an approximately 10% increase in forward head posture from their
      relaxed sitting postures when working with the computer display, but there were
      no significant changes in posture as a result of time-at-work.

PMID- 11831211
TI  - Sequence effects in categorization of simple perceptual stimuli.
AB  - Categorization research typically assumes that the cognitive system has access to
      a (more or less noisy) representation of the absolute magnitudes of the
      properties of stimuli and that this information is used in reaching a
      categorization decision. However, research on identification of simple perceptual
      stimuli suggests that people have very poor representations of absolute magnitude
      information and that judgments about absolute magnitude are strongly influenced
      by preceding material. The experiments presented here investigate such sequence
      effects in categorization tasks. Strong sequence effects were found.
      Classification of a borderline stimulus was more accurate when preceded by a
      distant member of the opposite category than by a distant member of the same
      category. It is argued that this category contrast effect cannot be accounted for
      by extant exemplar or decision-bound models of categorization. The effect
      suggests the use of relative magnitude information in categorization. A memory
      and contrast model illustrates how relative magnitude information may be used in
      categorization.

PMID- 11831212
TI  - Semantic and syntactic forces in noun phrase production.
AB  - Three experiments investigated semantic and syntactic effects in the production
      of phrases in Dutch. Bilingual participants were presented with English nouns and
      were asked to produce an adjective + noun phrase in Dutch including the
      translation of the noun. In 2 experiments, the authors blocked items by either
      semantic category or grammatical gender. Participants performed the task slower
      when the target nouns were of the same semantic category than when they were from
      different categories and faster when the target nouns had the same gender than
      when they had different genders. In a final experiment, both manipulations were
      crossed. The authors replicated the results of the first 2 experiments, and no
      interaction was found. These findings suggest a feedforward flow of activation
      between lexico-semantic and lexico-syntactic information.

PMID- 11831213
TI  - Fortification of food with vitamin B12 in addition to folic acid might reduce
      cardiovascular disease risk.

PMID- 11831214
TI  - MTBE ambient water quality criteria development: a public/private partnership.
AB  - A public/private partnership was established in 1997, under the administrative
      oversight of the American Petroleum Institute (API), to develop aquatic toxicity
      data sufficient to calculate ambient water quality criteria for methyl tertiary
      butyl ether (MTBE), a gasoline oxygenate. The MTBE Water Quality Criteria Work
      Group consisted of representatives from private companies, trade associations,
      and USEPA. Funding was provided by the private entities, while aquatic
      biological/toxicological expertise was provided by industry and USEPA scientists.
      This public/private partnership constituted a nonadversarial, cost-effective, and
      efficient process for generating the toxicity data necessary for deriving
      freshwater and marine ambient water quality criteria. Existing aquatic toxicity
      data were evaluated for acceptability, consistent with USEPA guidance, and
      nineteen freshwater and marine tests were conducted by commercial laboratories as
      part of this effort to satisfy the federal criteria database requirements.
      Definitive test data were developed and reported under the oversight of industry
      study monitors and Good Laboratory Practice standards auditors, and with USEPA
      scientists participating in advisory and critical review roles. Calculated,
      preliminary freshwater criteria for acute (Criterion Maximum Concentration) and
      chronic (Criterion Continuous Concentration) exposure effect protection are 151
      and 51 mg MTBE/L, respectively. Calculated, preliminary marine criteria for acute
      and chronic exposure effect protection are 53 and 18 mg MTBE/L, respectively.
      These criteria values may be used for surface water quality management purposes,
      and they indicate that ambient MTBE concentrations documented in U. S. surface
      waters to date do not constitute a risk to aquatic organisms.

PMID- 11831215
TI  - An X-ray absorption spectroscopy study of neptunium(V) reactions with Mackinawite
      (FeS).
AB  - Neptunium is a transuranium element, produced in tonne quantities in nuclear
      reactors. Because it has access to a range of oxidation states, neptunium may
      undergo redox transformations in the environment and these can have far-reaching
      effects on its environmental mobility. Here, the reaction of NpO2+ (the soluble
      and thermodynamically stable neptunium species in oxic systems) with
      microcrystalline mackinawite is studied. Uptake of neptunium from solution is
      relatively low (approximately 10% of the total initially present in solution) and
      independent of initial solution concentration over the range 0.27-2.74 mM and of
      equilibration time. X-ray absorption spectroscopy (XAS) of the solid sulfide
      samples indicates nearest neighbor oxygen atoms at distances around 2.25-2.26 A,
      sulfur atoms at around 2.61-2.64 A, and two more distant shells fitted with iron,
      at 3.91-3.95 A and 4.15-4.16 A. These observations suggest that on interaction
      with the sulfide surface reduction of Np(V) to Np(IV) occurs, accompanied by loss
      of axial oxygen atoms. Neptunium coordinates directly to surface sulfide atoms,
      in contrast to the behavior previously observed for uranium under similar
      conditions. These results demonstrate the importance and variability of the
      speciation of redox sensitive actinides under anoxic conditions.

PMID- 11831216
TI  - Indoor particulate matter of outdoor origin: importance of size-dependent removal
      mechanisms.
AB  - Adverse human health effects have been observed to correlate with levels of
      outdoor particulate matter (PM), even though most human exposure to PM of outdoor
      origin occurs indoors. In this study, we apply a model and empirical data to
      explore the indoor PM levels of outdoor origin for two major building types:
      offices and residences. Typical ventilation rates for each building type are
      obtained from the literature. Published data are combined with theoretical
      analyses to develop representative particle penetration coefficients, deposition
      loss rates, and ventilation-system filter efficiencies for a broad particle size
      range (i.e., 0.001-10 microm). We apply archetypal outdoor number, surface area,
      and mass PM size distributions for both urban and rural airsheds. We also use
      data on mass-weighted size distributions for specific chemical constituents of
      PM: sulfate and elemental carbon. Predictions of the size-resolved indoor
      proportion of outdoor particles (IPOP) for various conditions and ambient
      particle distributions are then computed. The IPOP depends strongly on the
      ambient particle size distribution, building type and operational parameters, and
      PM metric. We conclude that an accurate determination of exposure to particles of
      ambient origin requires explicit consideration of how removal processes in
      buildings vary with particle size.

PMID- 11831217
TI  - Solid-solution partitioning of organic matter in soils as influenced by an
      increase in pH or Ca concentration.
AB  - Organic matter is an important component of soil with regard to the binding of
      contaminants. Hence, the partitioning of organic matter influences the
      partitioning of soil contaminants. The partitioning of organic matter is, among
      other factors, influenced by the ionic composition and ionic strength of the soil
      solution. This study focuses on the behavior of organic matter after a change in
      the ionic composition of the soil solution, particularly in Ca concentration and
      pH. Different amounts of Ca(NO3)2 and NaOH were added to soil suspensions. The
      dissolved organic carbon (DOC) concentration increased with increasing pH
      (addition of NaOH), whereas an increase in Ca (addition of Ca(NO3)2) had the
      opposite effect. A stronger increase in DOC was observed if a single dose of NaOH
      was added, compared to a gradual addition of the same amount of NaOH. Cation
      binding by organic matter in the supernatant was calculated using the NICA-Donnan
      model. The log DOC concentration appeared to be correlated to the Donnan
      potential, calculated under the assumption that all DOC equals humic acid. This
      correlation was found for all eight neutral to acidic soils used in this study,
      although the slopes and elevations of the regression lines varied. The slope
      varied by a factor of 2 and the elevation appeared to be strongly influenced by
      the DOC concentration in the untreated soils, which is related to the total
      organic matter in the soil. Finally, we predicted the Donnan potential on the
      basis of an extraction of untreated soil with 0.03 M NaNO3, and the total
      additions of Ca(NO3)2 and NaOH. Comparison of these predictions with speciation
      calculations in solution showed a good correlation, indicating that a combination
      of one batch experiment and the presented calculation procedure can provide good
      estimations of DOC concentrations after addition of chemicals.

PMID- 11831218
TI  - Aerobic granulation in a sequencing batch airlift reactor.
AB  - Aerobic granular sludge was cultivated in an intensely mixed sequencing batch
      airlift reactor (SBAR). A COD loading of 2.5 kg Acetate-COD/(m3 d) was applied.
      Granules developed in the reactor within one week after inoculation with
      suspended activated sludge from a conventional wastewater treatment plant.
      Selection of the dense granules from the biomass mixture occurs because of the
      differences in settling velocities between granules (fast settling biomass), and
      filaments and flocs (slow settling biomass). At 'steady state' the granules had
      an average diameter of 2.5 mm, a biomass density of 60g VSS/I of granules, and a
      settling rate of > 10 m/h. The biomass consisted of both heterotrophic and
      nitrifying bacteria. The reactor was operated over a long period during which the
      granular sludge proved to remain stable. The performance of the intermittently
      fed SBAR was compared to that of the continuously fed biofilm airlift suspension
      reactor (BASR). The most importance difference was that the density of the
      granules in the SBAR was much higher than the density of the biofilms in the
      BASR. It is discussed that this could be due to the fact that the SBAR is
      intermittently fed, while the BASR is continuously fed.

PMID- 11831219
TI  - Stopped flow kinetic-spectrophotometric determination of Diquat in waters.
AB  - Using the measures of initial reaction rate, a kinetic-photometric method is
      developed that uses the reaction of Diquat with H2O2 in basic medium. The
      reaction rate is very high and therefore the stopped-flow mixing technique is
      required in order to make kinetic measurements. The reaction rate is obtained in
      20 s after the reactants are mixed and it allows the simple application of the
      method proposed to the routine analyses. The sensitivity of the method is very
      high being the detection limit 0.44 microgmL(-1) and the application range
      between 1 and 16 microgmL(-1). The time of measure per sample is 90s. The
      proposed kinetic-photometric method has been applied to the direct determination
      of this compound in river water, in the water of laundry of the olives, and in a
      commercial product. The results are very acceptable.

PMID- 11831220
TI  - Pharmacotherapy in the perinatal period--an exploratory study in midwifery.
AB  - OBJECTIVE: To gather information on the adherence to the Dutch national neonatal
      vitamin K policy and on the administration of prescription medication during
      labor by community midwives. METHODS: A telephone questionnaire under community
      midwives in the North of the Netherlands. RESULTS: In the main, the vitamin K
      practices follow the guidelines with respect to who receives the first dose and
      maintenance therapy. There is possibly underdosing. Midwives use their license to
      administer medicines during labor in moderation: 91% report to never use
      tocolytics, oxytocics or analgesics. CONCLUSION: In general, the national vitamin
      K policy is followed. Information gathered prospectively is needed on the use of
      pharmacotherapy by community midwives in the perinatal period.

PMID- 11831221
TI  - Cytochrome P4501A induction and testosterone hydroxylation in cultured
      hepatocytes of four fish species.
AB  - Primary hepatocytes of the rainbow trout (Oncorhynchus mykiss), flounder
      (Platychthis flesus), dab (Limanda limanda) and lemon sole (Microstomus kitt)
      were exposed to 3,3'4,4'5 pentachlorobiphenyl (PCB 126) or 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) for two days. This resulted in a dose
      dependent induction of cytochrome P4501A (CYP1A) activity, measured as
      ethoxyresorufin O-deethylase (EROD), or methoxyresorufin O-deethylase (MROD)
      activity. In all species, a linear relationship was observed between EROD and
      MROD activities, suggesting that the same CYP1A enzyme metabolizes the two alkoxy
      resorufin substrates. Exposures of hepatocytes of flounder or dab to TCDD,
      resulted in a 59-fold and 8.2-fold induction of EROD activity, respectively. This
      did not concur with a change in the in vitro testosterone hydroxylation profiles
      of both species. These and other in vitro data indicate that TCDD exposure does
      not influence monooxygenase activities involved in testosterone hydroxylation.
      Furthermore, CYP1A is of minor importance for testosterone hydroxylation in these
      fish species.

PMID- 11831222
TI  - Contemporary approach to the emergency department management of pediatric asthma.
AB  - Asthma continues to be an enormous health problem and economic burden in US
      society. EDs probably will continue to provide a substantial amount of care for
      those affected by the disease. Pediatric asthma patients frequently are
      encountered in EDs. Emergency physicians must remain current in their approach to
      providing expert care while the management of acute asthma exacerbations
      continues to evolve, older therapies are challenged and new therapies are
      developed, tested, and implemented.

PMID- 11831223
TI  - Complications of distraction osteogenesis: a changing pattern.
AB  - We reviewed Mr. Simpson's first 80 consecutive limb-lengthening procedures, using
      either a circular or a unilateral frame, and analyzed the complication rates. The
      initially high complication rate (100%) decreased significantly (P < .01) with
      experience. Incidence of axial deviation was reduced by changing the
      configuration of the fixators; delayed consolidations and fractures were reduced
      by prophylactic bone-grafting and by minimizing the associated complication of
      muscle contractures; severe pin-track infection was reduced by introducing a
      simple protocol; and muscle contractures and joint subluxation were reduced by
      adjusting the bone screw insertion sites and ensuring adequate early analgesia to
      allow early movement.

PMID- 11831224
TI  - Evaluation and application of bismuth as an internal standard for the
      determination of lead in wines by simultaneous electrothermal atomic absorption
      spectrometry.
AB  - A method for the direct determination of Pb in wines by simultaneous multi
      element atomic absorption spectrometry (SIMAAS) using a transversely heated
      graphite atomizer, Zeeman-effect background corrector and internal
      standardization is proposed. Bismuth was used as an internal standard and
      Pd(NO3)2 plus Mg(NO3)2 as chemical modifier to stabilize both the analyte and the
      internal standard. The implementation of two pyrolysis steps avoided any build-up
      of carbonaceous residues on the graphite platform. All diluted samples (1 + 1
      v/v) in 0.2% v/v HNO3 and reference solutions (5.0-50 microg l(-1) Pb in 0.2% v/v
      HNO3) were spiked with 25 microg l(-1) Bi. For a 20 microl aliquot dispensed into
      the graphite tube, a good correlation (r = 0.9997) was obtained between the ratio
      of the analyte signal to the internal standard signal and the analyte
      concentration of the reference solutions. The electrothermal behaviour of Pb and
      Bi in red, white and rose wines were compared. In addition, absorbance variations
      due to changes in experimental conditions, such as atomizer temperature,
      integration time, injected sample volume, radiation beam intensity, graphite tube
      surface, dilution and sample composition, were minimized by using Bi as internal
      standard. Relative standard deviations of measurements based on integrated
      absorbance varied from 0.1 to 3.4% and from 0.5 to 7.3% (n = 12) with and without
      internal standard correction, respectively. Good recoveries (91-104%) for Pb
      spikes were obtained. The characteristic mass was 45 pg Pb and the limit of
      detection based on integrated absorbance was 0.9 microg l(-1) Pb. Internal
      standardization increased the lifetime of the tube by 25%. Direct determinations
      of Pb in wines with and without internal standardization approaches were in
      agreement at the 95% confidence level. The repeatability and the tube lifetime
      were improved when using Bi as internal standard. The improvement in accuracy
      using an internal standard was only observed when the analytical results were
      affected by errors.

PMID- 11831225
TI  - Determination of liposome/water partition coefficients of organic acids and bases
      by solid-phase microextraction.
AB  - The extraction of two methylated anilines and three chlorinated phenols by solid
      phase microextraction (SPME) fibers coated with polyacrylate was investigated as
      a function of pH. Only the neutral species of the acids and bases partitioned
      into the polymer. Extraction kinetics were accelerated for the hydrophobic
      phenols at pH values around their acidity constant. This is presumably due to a
      reconstitution of the neutral species in the unstirred aqueous layer adjacent to
      the polymer surface by the charged species through the fast acid-base
      equilibrium. Although the charged species is not taken up into the polymer,
      liposome/water distribution ratios could be measured up to a pH value, where 99%
      of the compounds were present as charged species. The partition coefficients of
      the neutral and charged species were extrapolated from the pH profiles of the
      liposome/water distribution ratios. The resulting values were slightly lower than
      those measured with equilibrium dialysis. The discrepancies are discussed with
      respect to differences in the experimental conditions and the possibility of
      matrix effects during SPME measurements.

PMID- 11831227
TI  - The molecular outlook.

PMID- 11831228
TI  - A histological investigation on early tissue response to titanium implants in a
      rat intramedullary model.
AB  - Miniature grade 1 titanium screws were inserted in the tibias of 12 mature Wistar
      rats. Animals were sacrificed at 4, 7, and 21 days postimplantation. A
      combination of two morphological approaches was used to examine the tissue
      response to implants. One part of the prepared tissue specimens was routinely
      embedded in paraffin after a weak decalcification in EDTA. In this case, the
      implant was mechanically removed before embedding. The remainder of the specimens
      were embedded in polymethylmethacrylate resin, and ground sections were realized
      according to Donath's method. New bone formation occurred soon after
      implantation. Initially, on the fourth day, the presence of osteoid could be
      observed near the implant surface. On the seventh day, well-mineralized bone
      tissue was apposed directly on the implant surface. On the 21st day, the bone
      tissue became a highly organized lamellar bone.

PMID- 11831229
TI  - Evaluation of guided bone regeneration and/or bone grafts in the treatment of
      ligature-induced peri-implantitis defects: a morphometric study in dogs.
AB  - The goal of this study was to evaluate, morphometrically, hard-tissue healing
      following the treatment of ligature-induced peri-implantitis defects in dogs and
      guided bone regeneration and/or bone grafts. Five dogs were used, and the
      mandibular premolars were removed. Three months later, two titanium implants were
      installed on each side of the mandible, and after another 3 months, abutment
      connection was performed. Following abutment connection, experimental
      periimplantitis was induced by placing cotton ligatures in a submarginal
      position. Ligatures and abutments were removed after 1 month and the bony defects
      were randomly assigned to one of the following treatments: debridement (DE),
      debridement plus guided bone regeneration (GBR), debridement plus mineralized
      bone graft (BG), and debridement plus guided bone regeneration associated with
      mineralized bone graft (GBR/BG). The dogs were euthanatized after 5 months.
      Morphometric analysis did not reveal significant differences among the treatments
      neither with respect to the percentage of bone to implant contact (p = 0.996) nor
      to the bone area (p = 0.946) within the limits of the threads of the implant.
      Within the limits of this investigation, there is insufficient evidence to
      indicate that any of the treatments presented an improved response in dealing
      with bony defects resulting from peri-implantitis.

PMID- 11831230
TI  - Bone changes around hydroxyapatite and titanium implants after abutment placement
      in rabbits-observations using histological and three-dimensional examinations.
AB  - We have previously developed a computer-aided system for examination of the three
      dimensional bone structure around implants and observed the bone changes in the
      healing period after implant placement. This paper describes the bone changes
      around hydroxyapatite (HA) and titanium (Ti) implants after abutment placement
      using histological and three-dimensional examinations. Twenty-four HA and Ti
      implants were embedded in the tibias of adult male New Zealand white rabbits.
      After 8 weeks, the abutment had passed through periosteum and was placed under
      the skin. Rabbits were sacrificed 4 and 8 weeks following abutment placement. In
      conclusion, histological examination showed that, at 4 weeks after abutment
      placement, bone resorption around the implant neck was seen in both HA and Ti
      implants, and at 8 weeks, excessive bone formation was seen around the implant
      neck. Three-dimensional bone examination showed that abutment placement may
      affect bone formation and cause additional bone hypertrophy in the bone marrow
      area.

PMID- 11831231
TI  - Bone regeneration using Bioglass: an experimental study in rabbit tibia.
AB  - Bioglass (BG) has been shown recently to be osteoconductive and osteopromotive in
      different experimental and clinical conditions. The aim of the present study was
      to evaluate BG particles in bone defects in rabbit tibia. In control sites, bone
      was observed only in the peripheral areas of the defects, while in test sites,
      newly formed bone was found around all BG particles, even those located in the
      central portion of the defect. Osteoblasts were actively secreting osteoid matrix
      directly on the granules' surface. BG seems to be a highly osteoconductive
      material.

PMID- 11831232
TI  - A method for estimating preoperative bone volume for implant surgery.
AB  - This is a simple method for estimating preoperatively the underlying bone volume
      of a proposed edentulous site for dental implant placement. It entails a
      localized imprint of the ridge, measurement of the depth of the overlying
      gingival of the site, and correlating the measurements on a tracing of the ridge
      arch taken from the imprint. The resultant shape shows a slice of the underlying
      bone, giving the surgeon insight regarding the width of implant the site will
      accept, angulation, and the need for bone augmentation.

PMID- 11831234
TI  - Placement of implants into ridges grafted with bioplant HTR synthetic bone:
      histological long-term case history reports.
AB  - Following alveolar ridge grafting procedures for ridge preservation, for example,
      the immediate filling of extraction sockets, and ridge augmentation, for example,
      the building up of the atrophic jawbone, punch biopsies were obtained at various
      times postextraction prior to the placement of endosseous root-form implants.
      These histological sections provided an opportunity to study the bony
      regenerative response to an osteoconductive synthetic graft material and longer
      term interactions over a period from 8 months to 12 years. The formation and
      remodeling of healthy dense lamina of bone in areas where bone voids previously
      existed either from healed or immediate extraction sockets or where there was
      jawbone atrophy resulting from multiple tooth loss was observed. The grafting
      procedures enabled dentists to place implants into sites that would have been
      impossible if not for these preimplant grafting procedures. The jawbone areas
      studied involved grafted single sites and quadrants as well as full arch
      augmentation with a calcified microporous copolymer (Bioplant HTR Synthetic Bone,
      Bioplant Inc, South Norwalk, Conn) graft material. Retrospective case reports of
      24 patients were followed radiographically and clinically to 12 years post
      alveolar-ridge grafting and subsequently to 5 years after implants were placed
      into these augmented ridges. Implant and grafting histories from 4.7 months to 17
      years are reported for three of these patients. General applications of synthetic
      bone grafting before implant placement are recommended.

PMID- 11831233
TI  - Mandibular bone growth induced by a hydroxylapatite-coated subperiosteal implant:
      a case report.
AB  - History of the tripodal mandibular subperiosteal implant and the evolution of its
      design are discussed. Basic principles of bone physiology are reviewed especially
      as they relate to bone response to loading. Modeling and remodeling are
      controlled by a strain-related environment. Modeling can alter the shape and
      volume of bone. This aspect of bone growth has been reported with transosteal
      implants. A case report is presented in which apparent bone growth occurred
      following placement of a hydroxylapatite-coated subperiosteal implant. The
      implant was successfully revised following an acute infection around one of the
      permucosal sites.

PMID- 11831235
TI  - The ankylos endosseous dental implant: assessment of stability up to 18 months
      with the Periotest.
AB  - Osseointegration is an ongoing histometric process that may vary during clinical
      function. The implant must be stable at uncovering, which reflects the status of
      bone-implant interface. The physiology of bone healing associated with endosseous
      implants suggests that this process occurs between 8 and 12 months, and Periotest
      values (PTVs) tend to reflect changes in the stability of the bone-implant
      interface. Stability generally increases gradually from the time of uncovering to
      an optimal PTV that occurs at a point close to 12 months. This stable interface
      must remain intact for long-term clinical survival. Rapid development of this
      optimal PTV is highly desirable in order to prevent premature overloading of the
      bone-implant interface. The Ankylos implant is a new screw-type implant design in
      which the thread pitch and length vary to maximize trabecular bone contact. The
      purpose of this report is to evaluate to 18 months the stability (PTVs) of this
      implant design. More than 457 implants were placed and followed for a period of
      18 months by the multicentered, multidisciplinary Ankylos Implant Clinical
      Research Group (AICRG). Implant stability (PTVs) was assessed using the Periotest
      at abutment connection and at 3, 6, 9, 12, and 18 months after uncovering. The
      Periotest values for all implants rapidly reached an optimal status between
      uncovering (-3.1 PTVs) and 3 months (-3.4 PTVs). This rapid increase in stability
      has not previously been reported for other implant designs. The mandibular arch
      was more negative (-3.8 PTVs) at uncovering as compared with the PTVs for the
      maxillary arch (-1.7 PTVs). Negative PTVs were recorded (1) as length and
      diameter increased, (2) as bone density increased, (3) in certain jaw regions,
      (4) as the number of implants/case increased, and (5) for implants stabile at
      placement. The Ankylos screw implant design produced rapid stabilization 3 months
      after uncovering.

PMID- 11831236
TI  - Precise dental implant placement in bone using surgical guides in conjunction
      with medical imaging techniques.
AB  - The use of medical imaging techniques to make a very precise surgical guide for
      implant placement is described. This template is the combination of a currently
      used template and a very simple mechanical system designed to transfer a
      preoperatively defined implant position onto the surgical site. With the planning
      software, the practitioner determines the implant position according both to the
      ideal position dictated by the final restorative prosthesis and the available
      volume of bone. The surgical template then communicates the actual implant
      position to the surgical site. The template can be used not only in critical
      anatomical situations but also in placing the implant in an ideal position on
      bone because it eliminates possible manual placement errors and matches planning
      to prosthetic requirements.

PMID- 11831237
TI  - Clinical evaluation of vascularized bone grafts and osseointegrated implants.
AB  - We evaluated mandibular rehabilitation using vascularized bone graft and
      osseointegrated implants. Questionnaires were used to evaluate the masticatory
      function, and we measured the occlusal force in each patient. In addition, we
      measured the height of grafted bone to assess the possible relationship between
      masticatory rehabilitation and the change in bony height. Five of 13 patients
      showed over 12.0% increase in bony height after superstructure fabrication. Most
      of the patients who underwent tongue resection scored low points on the
      questionnaire. Also, most patients with resection, including resection of the
      angles of the mandible, showed a lower occlusal force than those without.

PMID- 11831239
TI  - [Comparative ophthalmology in the Middle Ages].
AB  - Descriptions of animal eyes in the Middle Ages in the learned work Physiologus
      from the 4th century, based on Aristoteles, Plutarc, the Bible etc. are commented
      on. The modern biologist is horrified, the historian understands the ethical -
      religious aspects behind the edifying stories concerning the lion, gazelle,
      eagle, snake, lizard, swallow etc. Medical science and theology were not
      separated in the Middle Ages.

PMID- 11831240
TI  - [Stefan Jorgensen 1887-1944: a clearing-murder].
AB  - In Domus Medica, there is a white marble plaque with the names of Danish doctors
      who lost their lives during the occupation. Among these names is my father's
      "Stefan Jorgensen". The murder of my father was what is called a 'clearing'
      murder, i.e., the murder of a Dane chosen at random as retaliation for the
      killing of a German or an informer. My father was murdered at the door of his
      consulting rooms in his home on 24 April 1944. An article in Berlingske Tidende
      on 25 April stated that the murder occurred in the doctor's consulting rooms,
      where in the end two young men and a somewhat older man sat in the waiting room.
      When the doctor came out to receive the next patient, one of the younger men got
      up and shot at the doctor's head four times, where upon the doctor fell down, and
      the murderer fled. In 1993, a book by Jorgen Rojel, "Holger Danske rejser sig",
      was published. In the book is stated, On 24 April "Johs' father was murdered by
      Henning Brondum". Hans Edvard Teglers writes in his book "Sabotage" from 1961,
      "On 24 April 1944, Doctor Stefan Jorgensen was murdered in his consulting rooms
      in Vaeldegaardsvej in Gentofte. The two terrorists, Brondum and Bothilsen
      Nielsen, had sat in the waiting room. It later came to light that Dr. Stefan
      Jorgensen had been on the Gestapo's list of possible victims for the so-called
      'clearing murders', the so-called A-file".

PMID- 11831241
TI  - [Hjalmar Maag: a Danish pioneer].
AB  - In the year 1900 a young man was on the operating table for a minor operation at
      the hospital in the small provincial town of Naestved. He was anaesthetized with
      Chloroform. After 15 minutes his pulse and respiration suddenly failed. All the
      usual methods of resuscitation were tried, but to no avail. Afterwards a
      tracheostomy and an inflation with air through the cannula were performed, also
      without success. The surgeon then decided to open thorax and perform direct
      internal heat massage. The heart was reactivated and went on working for 8 hours.
      Dr. Maag did not succeed in saving his patient's life, but he is rightly
      considered to be the first person to have revived a heart that had completely
      ceased to work.

PMID- 11831242
TI  - [The most dramatic train accident in Denmark: Gentofte 1897].
AB  - One of the most dramatic train accidents in Denmark happened at a railway station
      close to midnight on the 11th of July 1897. Forty passengers were killed and
      approximately 150 people were more or less seriously wounded. Three different
      actors involved in the accident (a stoker of the collided engine, a journalist
      and a physician) have later described the scenario of the disaster according to
      their professional backgrounds. The principles of disaster management, the
      emergency response including a rather quick involvement from different types of
      relevant professions, the triage and the prehospital treatment of victims seemed
      to have been adequate according to the framework at that time. The descriptions
      refer shortly to the psychopathological reactions following a life threatening
      experience which today are well defined and described as symptoms of PTSD (Post
      Traumatic Stress Disorder).

PMID- 11831243
TI  - [The tobacco's inconsistent properties].
AB  - Why do creative heavy smokers often persist with unsound and unsanitary
      attitudes? The group of heavy smokers express uncomprehensive and explicit
      behaviour in their stubborn way "it's not us" - just as some paintings with
      contradicting titles. A critical conclusion must be, however, tobacco can also
      supply with a regulation of thoughts and approaches in important social, cultural
      and scientific projects. This paper includes two suggestive cases selected from
      the scientific past in Denmark, displaying two famous and glorious personalities
      with the profound integration of smoking habits. Time has changed, however, and
      recent investigations now support the idea to fight down the lock of bad habits
      in heavy smokers. Thousands of lives can then be saved during the next 10-20
      years.

PMID- 11831244
TI  - An objective determination of +Gz acceleration tolerance.
AB  - Until recently, human +Gz acceleration tolerance has relied solely on subjective
      criteria relating to loss of vision. By use of newly developed noninvasive
      instrumentation using a transcutaneous Doppler flow system, objective end point
      criteria have been developed based on measured blood flow to the head. The system
      consists of miniature 8 MHz Doppler sensors (2 x 1 x 0.5 cm) placed on the
      forehead over both frontal branches of the temporal arteries to detect blood flow
      velocity from back scattered ultrasound. Its use has allowed for correlation of
      altered, decreased and actual reversal of eye level blood flow with subsequent
      central light loss. Over 100 subjects have now been studied during more than
      2,000 centrifuge runs. Objective changes in temporal artery flow velocity
      consistently preceded visual degradation for each subject during all acceleration
      profiles. No subject has gone unconscious without first exhibiting a minimum 6
      sec of total flow cessation. Retrograde flow followed by complete flow cessation
      always preceded central light loss. Results indicate that this method can be
      successfully used with a wide variety of tasks during exposure to +Gz
      acceleration. It is recommended for use during evaluation of protective maneuvers
      or devices on the centrifuge or during actual flight in high performance
      aircraft. It may also serve as a potential safety monitor during space Shuttle re
      entry if there is doubt about a passenger's cardiovascular status.

PMID- 11831246
TI  - Motion sickness susceptibility during rotation at 30 rpm in free-fall parabolic
      flight.
AB  - Free fall per se whether in parabolic or orbital flight may be regarded as a
      "partial" motion environment with respect to eliciting motion sickness, requiring
      an additional component to render this environment "complete" or stressful.
      Parabolic flight in toto falls in the category of a "complete" motion environment
      in that some persons became motion sick with head fixed and eyes closed. In the
      present experiment we selected subjects who were symptom free or nearly symptom
      free in the KC-135 with head fixed. All tests were conducted with the subject
      rotating at 30 rpm in a rotating litter chair, and comparisons were made between
      head-fixed and head-moving conditions (right-left) in the free-fall phase of
      parabolic flight and under simulated free-fall phases in the laboratory. With
      head fixed most subjects were insusceptible; with head moving left-right
      susceptibility was slightly higher in the laboratory than aloft. An additional
      comparison was made correlating susceptibility in the free-fall phases of
      parabolic flight with susceptibility to experimental motion sickness in Skylab.
      In both situations cross-coupled angular accelerations were generated by
      executing head and body movements out of the plane of rotation. In parabolic
      flight 9 of 15 subjects reached an endpoint just short of frank motion sickness.
      In the Skylab workshop all eight of the astronauts tested were symptom free at
      the end of the test. The explanation for the difference in susceptibility rests
      in two factors: (1) Basic susceptibility in free fall is lower than on the
      ground, and (2) in Skylab the astronauts who needed to adapt had achieved this
      goal prior to the first test on Mission-Day 8.

PMID- 11831247
TI  - Standard integrates patient lab-work history with health record network.

PMID- 11831245
TI  - Erythropoietic effects of space flight.
AB  - Various factors which are important in the regulation of erythropoiesis have been
      studied in dehydrated mice in the belief that some information would be gained
      relevant to the erythropoietic effects of space flight. Dehydration reduced the
      plasma volume and, because changes in red cell volume were minimal, the
      hematocrit was elevated. Thus a state of relative erythrocytosis was produced.
      Our understanding of the mechanism whereby these changes decreased red cell
      production is uncertain and appears to differ somewhat from the erythroid
      suppression seen following elevation of the hematocrit in animals with an
      absolute erythrocytosis. It is suggested that factors outside of the normal
      erythropoietic control pathway (such as energy balance) may play an important
      role in the decrease in red cell volume seen in man following space flight.

PMID- 11831248
TI  - Standards for personal health Web-sites under way.

PMID- 11831249
TI  - Data-element standard promotes uniform EMS documentation.

PMID- 11831250
TI  - Clinical laboratory subcommittees merge.

PMID- 11831251
TI  - Nitric oxide: a greenhouse gas is used in the treatment of respiratory failure.
AB  - Medical science has long made the improbable probable, saving lives and improving
      quality of life. Upon the introduction of medical devices that can deliver safe
      quantities of the poisonous gas nitric oxide to help patients with respiratory
      and other illnesses, the FDA requested ASTM Committee F29 on Anesthetic and
      Respiratory Equipment to provide standards for these devices. Dr. Daniel Supkis
      and Mark Graber explain the delicate process of delivering NO to patients and how
      ASTM standards now in development will increase the safety of this procedure.

PMID- 11831252
TI  - Abortion and the courts in Ireland.

PMID- 11831253
TI  - The rush to clone.

PMID- 11831254
TI  - Stem cell challenges.

PMID- 11831255
TI  - Bridging problems and models in medical ethics: four images of local ethics
      committees.
AB  - In the context of the continuing debate about how ethics committees in Italy
      should be structured (see Bulletin 160) Professor Incorvati, from the Comitato
      Nazionale per la Bioetica in Rome, considers four theoretical models of how such
      committees may be arranged, and why one in particular looks better placed to face
      the growing ethical problems that are emerging as a result of current
      developments in medicine.

PMID- 11831256
TI  - Stem cell research, in Parliament.
AB  - Late autumn and early winter have seen a flurry of Parliamentary activity about
      the law and ethics of embryonic stem cell research. This follows publication of
      the Chief Medical Officer's Expert Group's report on the subject (see Bulletin
      160), the first recommendation of which was that such research should be
      permitted by means of a regulation under the Human Fertilisation and Embryology
      Act 1990. The following records some of the episodes in that activity with
      extracts from some of the speeches made.

PMID- 11831257
TI  - Retaining organs for no good reason.

PMID- 11831258
TI  - Bioethics at the European Commission.

PMID- 11831259
TI  - The right to refuse treatment and blood transfusion.
AB  - A Hungarian bioethicist looks at the Hungarian law on the refusal of treatment,
      and of blood transfusion by Jehovah's Witnesses.

PMID- 11831260
TI  - Do researchers feel an LREC hinders research?
AB  - BACKGROUND: All medical professionals in the UK who wish to undertake clinical
      trials involving NHS patients must first obtain ethical approval. Although Local
      Research Ethics Committees (LRECs) play a crucial role, few studies have
      attempted to determine what researchers think about the effectiveness of their
      ethics committee. OBJECTIVE: To explore researchers' views as to the
      effectiveness or otherwise of their LREC. SUBJECTS: 78 experienced medical
      researchers. FINDINGS: While most researchers did not feel that the LREC made it
      more difficult to carry out their research, without good cause, a substantial
      minority was critical of the Committee, with many feeling that its approach was
      overly pedantic. CONCLUSION: There may be a need for greater dialogue between
      ethics committees and researchers, so that researchers understand why committees
      ask for certain information, and committees are aware of problems their
      requirements may cause.

PMID- 11831261
TI  - Ethical aspects of human stem cell research and use. Official statement.

PMID- 11831262
TI  - Genetics and human behavior.

PMID- 11831263
TI  - Bristol interim report.

PMID- 11831264
TI  - Genetics and Society Project.
AB  - Faced with rapid advances in human genetics, policy makers are struggling to come
      to grips with a host of complex ethical, legal and social questions. The HUMGEN
      website gives policy makers and the public access to legislation, policy,
      guidelines and recommendations of government and nongovernmental organizations
      worldwide.

PMID- 11831265
TI  - Method and complexity in bioethics: the example of community genetics.
AB  - This article describes the need to develop a new methodology in bioethics that
      can consider multiple interactions, creativity and the organisation specific to
      complex systems. Community genetics is taken as an example of complexity in
      bioethics. Community genetics involves large populations and illustrates certain
      characteristics of complex adaptive systems which are discussed in the article.

PMID- 11831266
TI  - Empowering the public to be informed consumers of genetic technologies and
      services.
AB  - OBJECTIVE: The genetics community, together with lay advocacy organizations and
      the general public, should strategically plan a focused, culturally competent,
      community-based public genetic literacy program. METHODS: Inclusive of all
      stakeholders (consumers, professionals, disability communities, disenfranchised
      communities), society can advance this objective through a proactive, focused and
      coordinated outreach to build public awareness and understanding. RESULTS:
      Genetic Alliance programs support consumers with genetic disorders, raise health
      professional awareness of their concerns, educate the public about emerging
      genetic information and technologies, increase access to high quality information
      resources, and advocate for public policies that ensure the promises of genetics.
      CONCLUSION: The challenge before the genetics community is to be proactive,
      clear, and inclusive. The public should be empowered to make informed choices,
      allowing the potential benefits of genetic technologies and services to become
      manifest in improved healthcare and quality of life.

PMID- 11831267
TI  - Artificial insemination, egg donation and adoption.

PMID- 11831268
TI  - Being of sound mind and judgment--rethinking sanctions in the case of assisted
      suicide.

PMID- 11831269
TI  - To love the stranger.

PMID- 11831270
TI  - Am I my brother's keeper? A Jewish view on the distribution of health care.

PMID- 11831271
TI  - Health care and Mrs. Job--the conflict of personal categories.

PMID- 11831272
TI  - Moral and religious values in health care reform--a Roman Catholic perspective.

PMID- 11831273
TI  - Who should have access to what mental health services? The journey from Oz to
      Ephesus.

PMID- 11831274
TI  - Introduction.

PMID- 11831275
TI  - Health care reform and finitude.

PMID- 11831276
TI  - Am I my brother's keeper?

PMID- 11831277
TI  - Health care--right or privilege?

PMID- 11831278
TI  - The changing health care safety net.

PMID- 11831279
TI  - The distribution of health benefits by American governments--rationales and
      outcomes.

PMID- 11831280
TI  - National Bioethics Advisory Commission Report: Ethical and policy issues in
      international research.

PMID- 11831281
TI  - Dialogue on suicide and abortion.

PMID- 11831282
TI  - Confidentiality and threatened suicide.

PMID- 11831284
TI  - Beating the ban.

PMID- 11831285
TI  - A way forward.

PMID- 11831288
TI  - Imprisoning the mentally ill: does it matter?

PMID- 11831289
TI  - Against the separation of Jodie and Mary.

PMID- 11831290
TI  - Separating the twins Jodie and Mary.

PMID- 11831291
TI  - Francis Bacon's concept of objectivity and the idols of the mind.
AB  - This paper examines the concept of objectivity traceable in Francis Bacon's
      natural philosophy. After some historical background on this concept, it
      considers the question of whether it is not an anachronism to attribute such a
      concept to Bacon, since the word 'objectivity' is a later coinage and does not
      appear anywhere in his writings. The essay gives reasons for answering this
      question in the negative, and then criticizes the accounts given of Bacon's
      understanding of objectivity by Lorraine Daston and Julie Robin Solomon. It
      argues that this understanding is most directly and fully expressed in his
      discussion of the idols of the mind. In this connection, the paper notes Bacon's
      critical attitude to sixteenth-century scepticism and its relevance to the idea
      of objectivity implicit in his comments on the idols. In conclusion, the paper
      argues that Bacon was not a pure empiricist and describes the place assigned to
      theories and hypotheses in his natural philosophy.

PMID- 11831292
TI  - Theological debate over embryo adoption.

PMID- 11831293
TI  - Designing our descendants.

PMID- 11831294
TI  - Schizophrenia and the narrative of enlightened geneticization.
AB  - In this paper I explore the way in which scientists attempt to construct
      schizophrenia as a genetic disease using various discursive strategies. These
      strategies involve: referring back to earlier twin and adoption studies on
      schizophrenia inheritance; constructing genetic models to allow some role for
      single gene versions of the condition; a cautious and responsible limit on the
      strength of current research; and the construction of a range of bordering
      conditions which contribute to the genetic risk of schizophrenia. These various
      rhetorics produce a 'narrative' about schizophrenia which subtly prioritizes
      genetic explanations, while appearing to allow a role for non-genetic factors; I
      term this the 'narrative of enlightened geneticization'. This research has
      implications for scientific controversies, specifically the way in which critics
      attack schizophrenia genetics, since many of their points are already
      incorporated into the narrative. It also contributes to the ongoing debate over
      the role of social science research in the study of geneticization.

PMID- 11831295
TI  - The Australian Rabbit Calicivirus Disease Program: a story about technoscience
      and culture.
AB  - The paper discusses the Australian Rabbit Calicivirus Disease (RCD) Program, an
      attempt at the biological control of wild rabbits, as an example of how
      technoscience in 'Mode-2 society' works. My aim is to illuminate the variety of,
      and the connections between, the diverse activities that the technoscientific
      actors engage in. The RCD Program brought a new entity into Australia; it was
      pursued by a network of actors across institutional boundaries, and it produced a
      public image linked to widely accepted cultural knowledge. I argue that the
      research articulating 'rabbit calicivirus' as a biological control agent, the
      extent of the supporting network and the alignment of the Program with cultural
      narratives about rabbits, were three aspects of the same process, and equally
      important. However, it also makes sense to understand each aspect in terms of
      both the audience addressed, and the temporal succession: hence, they can be
      distinguished as distinct aspects. Detailed study of projects like the RCD
      Program is necessary to further our understanding of the dynamics of
      technoscience in contemporary culture.

PMID- 11831296
TI  - Responsibilities of practitioners.

PMID- 11831297
TI  - Prosthetic reconstruction of the edentulous maxilla.
AB  - Presurgical planning for the treatment of the maxillary edentulous patient is
      followed with an entire step-by-step construction of the maxillary prosthesis. I
      emphasize prosthetic try-ins that ensure proper abutment placement to maximize
      superior aesthetics and occlusion. Techniques demonstrated will reduce both chair
      time and stress to the dentist and patient. Also, proper coordination with the
      laboratory technician frees the doctor from doing time-consuming procedures
      intraorally. A temporary prosthesis is constructed and used as a guide for the
      final prosthesis. The efficiency of the following indirect technique allows this
      service to reach a greater number of patients.

PMID- 11831298
TI  - Single tooth-by-tooth crowns over Frialit-2 implants.
AB  - Optimizing aesthetics in the anterior maxilla can be a challenge because of
      tissue contouring problems. Dental implants allow for restoration of edentulous
      areas, thus improving function. Some compromises may result as a result of the
      necessity of predicting the stability of the replacement restorations. The
      Frialit-2 dental implant system with the internal hex design provides excellent
      stability for single-tooth restorations. Aesthetics are maximized using Procera
      Allceram crowns. This case study describes in detail the following: diagnosing
      and treatment planning for a challenging trauma case; surgical preparation and
      placement of two Frialit-2 dental implants in the maxillary left central and
      lateral incisor areas; primary impression techniques and fabrication of a
      temporary prosthesis over ProTect abutments; second-phase opening; final
      impressions; and fabrication of two single crowns.

PMID- 11831299
TI  - Maxillary insufficiency implant and tooth-retained maxillary overdenture: a
      clinical case report.
AB  - The following represents a clinical case report of a maxillary insufficiency
      implant and tooth-retained maxillary overdenture. The case required surgical and
      prosthetic treatment and was successfully completed over a 2-year time. A
      combination of dental implant techniques were utilized to achieve form, function,
      comfort, and aesthetics. These techniques included ridge modification with bone
      grafting, endosseous root and blade form implant surgical placement, and the
      construction of a bar-retained overdenture on a severe hypoplastic maxilla.

PMID- 11831301
TI  - Use of the mandibular ramus as a donor site for onlay bone grafting.
AB  - Cortical bone grafts harvested from the posterior mandible offer several
      advantages for bone augmentation prior to implant placement. These grafts
      maintain their dense quality and exhibit minimal resorption upon incorporation.
      Considerable amounts of bone can be harvested from this area for use as an onlay
      graft. In addition, the ramus area has some inherent advantages over other donor
      sites. This article describes the indications and surgical technique for
      harvesting bone from the ramus region.

PMID- 11831300
TI  - Maintaining and attenuating periodontal tissues for aesthetic implant placement.
AB  - Alveolar ridge resorption and soft tissue recession after tooth extraction
      inevitably disrupted the harmonious pre-existing periodontal complex,
      compromising clinicians' ability to recreate successful aesthetic restorations.
      Although numerous surgical procedures had been advocated for the augmentation of
      both the alveolar ridge and its soft tissue to ideal contours, questions remain
      regarding viability and predictability of these procedures. This is especially
      critical in the maxillary anterior region, where a the condition of the soft
      tissue complex and its relationship to the implant restoration and its adjacent
      dentition often determines the implant's success. The described technique of
      retaining the root remnant and inducing the proliferation of the surrounding
      tissue in conjunction with immediate implant placement results in the
      preservation of existing soft and hard tissue, thus minimizing the necessity of
      grafting procedures and facilitating primary flap closure during implant
      placement.

PMID- 11831302
TI  - Use of microfocus computerized tomography as a new technique for characterizing
      bone tissue around oral implants.
AB  - Qualitative and quantitative analysis of peri-implant tissues around retrieved
      oral implants is typically done by means of light microscopy on thin histological
      sections containing the metal surface and the undecalcified bone. It remains,
      however, a labor-intensive and thus time-consuming job. Moreover, it is a
      destructive technique that allows tissue quantification in only a limited number
      of two-dimensional sections. As an alternative, we evaluated the bone structure
      around screw-shaped titanium implants by means of microfocus computerized
      tomography (micro-CT) because it presents a number of advantages compared to
      conventional sectioning techniques: micro-CT is nondestructive, fast, and allows
      a fully three-dimensional characterization of the bone structure around the
      implant. Images can be reconstructed in an arbitrary plane, and three-dimensional
      reconstructions are also possible. Because of its high resolution, individual
      trabeculae can be visualized. The accuracy of micro-CT was qualitatively
      evaluated by comparing histological sections with the corresponding CT slices for
      the same specimen. The overall trabecular structure is very similar according to
      both techniques. Even very close to the interface, the titanium implant does not
      seem to produce significant artifacts. Furthermore, because the complete digital
      data on the trabecular bone structure around the implant is available, it is
      possible to create finite-element models of the bone-implant system that model
      the trabeculae in detail so that mechanical stress transfer at the interface can
      be studied at the level of individual trabeculae. Therefore, micro-CT seems to be
      very promising for the in vitro assessment of the three-dimensional bone
      structure around oral implants. Further research will be needed to evaluate its
      accuracy in a more quantitative way.

PMID- 11831303
TI  - Scientific rationale for the surgical and prosthodontic protocol for immediately
      loaded root form implants in the completely edentulous patient.
AB  - This paper discusses a modified surgical and prosthodontic protocol to place
      implants in the completely edentulous patient. Methods for presurgical,
      prosthodontic workup, impression transfer technique, provisionalization, and
      attachment placement are also discussed.

PMID- 11831305
TI  - Visible light-curing.

PMID- 11831306
TI  - Learning to smile: the neuroanatomic basis for smile training.
AB  - This article demonstrates that although any layperson could recognize that the
      smile manifests mainly in the oral and periorbital regions, a comprehension of
      the neurologic and musculoskeletal elements lends the clinician insight into the
      many aspects of a smile. The neurologic control of a smile consists of a complex
      process involving many facets. As with any other complex neuromuscular activity,
      repetitions of the act can train the central nervous system, neural network, and
      muscular network in efficient performance of and correct musculoskeletal
      activation involved in the act itself. With functional knowledge of muscles
      dedicated to a pleasing full smile, together with a battery of easy and
      effortless exercises, the clinician is able to help the patient change behavior
      intended to camouflage perceived oral flaws. A patient needs reassurance that
      behind the guidance from the clinician lies medical evidence that such routine
      movement of muscles will indeed improve the smile. When asked why or how the
      exercise succeeds, the clinician can reassure the patient based on a working
      knowledge of the neurologic and muscular anatomy involved. CLINICAL SIGNIFICANCE:
      A functional knowledge of muscles dedicated to a pleasing full smile, together
      with a battery of easy and effortless exercises, provides the clinician with the
      ability to assist the patient in altering years of behavior intended to
      camouflage perceived oral flaws.

PMID- 11831307
TI  - Treatment planning for porcelain veneer restoration of crowded teeth by modifying
      stone models.
AB  - The three-dimensional result attainable through porcelain veneer restoration of
      crowded teeth can be preoperatively determined by diagnostically altering stone
      study models of the patient's dentition. Techniques for diagnostically preparing
      and waxing the stone dental models are described in this article, along with the
      corresponding postoperative restorative results of representative cases. CLINICAL
      SIGNIFICANCE: Patients with malaligned teeth who are not willing or able to
      undergo straightening of their teeth with orthodontics, nonetheless may be able
      to attain straight teeth concomitant with the restoration of their teeth with
      modified porcelain veneer restorations. This article describes a straight forward
      treatment planning technique for altering study casts preoperatively, to
      accurately predict and guide the postoperative outcome.

PMID- 11831308
TI  - Minimum color differences for discriminating mismatch between composite and tooth
      color.
AB  - PURPOSE: The purpose of this study was to determine if there are differences
      between patients and dental professionals in their ability to identify small
      color differences (deltaE) in composite resin restorative materials in vitro and
      to determine the deltaE that would indicate acceptability of color match between
      a restoration and an adjacent tooth. MATERIALS AND METHODS: Subjects were asked
      to evaluate composite resin disks to distinguish acceptability of deltaE between
      disk pairs. Color difference discrimination of dental professionals groups D1
      (dentists, n = 12) and D2 (dental auxiliaries, n = 12) was compared to that of
      dental patient groups P1 (patients, n = 12) and P2 (scientists, n = 12). Each
      group was pretested for normal color vision. Color differences between a standard
      and restoration disks of composite were measured in Colour Measurement Committee
      (CMC) (1:1) color units. Data were analyzed by logistic regression, and results
      were used to calculate a probability level for minimal acceptance or rejection of
      AE for all observers. Mean 50:50 deltaE replacement points (RP) for each group
      were obtained and analyzed by analysis of variance, and the Tukey pairwise
      comparison test was applied (alpha = 0.05 for all statistical analyses). RESULTS:
      There were significant differences found between the experimental groups (p =
      .020). Group D2 (mean 50:50 deltaE RP = 1.78) proved to be more discriminating in
      accepting differences between tooth and composite resin restorative material
      color than group P1 (mean 50:50 deltaE RP = 2.69). The mean 50:50 deltaE RP for
      all subjects was 2.29 CMC (1:1) units. CLINICAL SIGNIFICANCE: The ability to
      generate an excellent color match between a tooth-colored restoration and the
      tooth is critical to esthetic success. This study demonstrates that patients are
      not as discriminating in their ability to identify small color differences
      between composite restorations and the tooth as are dental professionals. Dental
      auxiliaries proved to be more discriminating in accepting differences between
      tooth and composite resin restorative material color than were patients.

PMID- 11831309
TI  - Four-year clinical evaluation of posterior resin-based composite restorations
      placed using the total-etch technique.
AB  - PURPOSE: To report the 4-year clinical performance of posterior resin-based
      composite restorations placed using the total-etch technique. MATERIALS AND
      METHODS: Over a period of 1 year, 726 restorations (248 molars, 478 premolars;
      260 Class I, 466 Class II; 540 replacements, 186 primary decay) were placed on
      conservative preparations, using the incremental placement technique in a
      clinical environment. Baseline data were collected, and the restorations were
      evaluated after 4 years. Z100 and Scotchbond Multi-Purpose (SBMP) (3M Dental
      Products, St. Paul, Minnesota) were used as the restorative system. The criteria
      evaluated were color match, marginal adaptation, anatomic form, cavosurface
      marginal discoloration, axial contour, interproximal contact, secondary caries,
      postoperative sensitivity, and tooth vitality. RESULTS: At baseline, 24% of the
      teeth restored presented postoperative sensitivity; 86% of the sensitive teeth
      were from the replacement group. At 4 years, all teeth were vital to cold test.
      Eighteen restorations (2.5%) presented clinically detectable marginal fracture.
      The shade was acceptable in all restorations. Cavosurface marginal discoloration
      was observed in 47 restorations (6.5% bravo scores). Axial contour, interproximal
      contact, and marginal adaptation received 100% alfa scores. No secondary caries
      was diagnosed in any of the teeth examined. None of the examined restorations
      required replacement. CLINICAL SIGNIFICANCE: Under controlled clinical
      conditions, posterior resin-based composite restorations placed with the total
      etch technique and restorative Z100/SBMP have the potential to present a high
      success rate at 4 years. None of the examined restorations required replacement,
      and there was no clinically detectable wear in any of the restorations.
      Simultaneous etching of enamel and dentin followed by the application of a resin
      adhesive can be considered an adequate modality of pulp protection in nonexposed
      tooth preparations.

PMID- 11831310
TI  - The metal-free practice: myth? Reality? Desirable goal?

PMID- 11831311
TI  - Packable composites.

PMID- 11831312
TI  - Tooth whitening: why, who, where, what, and how.

PMID- 11831313
TI  - Proof first, profit second.

PMID- 11831314
TI  - Was this recognition a good choice?

PMID- 11831315
TI  - Proliferation and differentiation of bone marrow cells on titanium plates treated
      with a wire-type electrical discharge machine.
AB  - For successful dental implants, it is necessary to obtain satisfactory
      osteointegration at the site of both the cortical and trabecular bones in the
      jaw. Bone marrow stromal cells differentiate into osteoblast-lineage cells and
      have an important role in bone remodeling. In this experiment, the responsiveness
      of bone marrow cells to a titanium plate with a rough surface was compared with
      that of a titanium plate with a smooth surface. The rough surface was created by
      treating with a wire-type electrical discharge machine, and the smooth plate was
      produced by polishing with 1.500-grade emery paper. The results indicated that,
      though bone marrow cells proliferated on both plates, the proliferation pattern
      and cell growing time on the plates were different. While the cells on the smooth
      plate proliferated along the grooves produced by polishing, the cells on the
      rough plate proliferated randomly and more rapidly. As bone marrow cells
      consisted of heterogeneous cell populations involving hematopoietic cells, we
      collected bone marrow mesenchymal stromal cells that proliferated on plastic
      dishes and studied the proliferation and differentiation of these cells. Stromal
      cells on the rough plate more actively proliferated than those on the smooth
      plate. In long-term culture, the cells on the rough plate showed higher alkaline
      phosphatase activity and produced cell nodules. The cells on the smooth plate
      were stripped off the plate without nodule formation. These results indicated
      that bone marrow stromal cells on the rough plate could more rapidly proliferate
      and differentiate into osteoblast-lineage cells compared with those on the smooth
      plate.

PMID- 11831316
TI  - Immediate postextraction implants: a histologic and histometric analysis in
      monkeys.
AB  - The aim of this study was to evaluate the reaction of peri-implant tissues to
      immediately placed titanium plasma-sprayed implants into extraction sockets. Six
      macaca fascicularis monkeys were used in the study. A total of 36 titanium plasma
      sprayed implants (PHI, Legnano, Italy) were inserted in both arches (18 in the
      posterior maxilla and 18 in the posterior mandible). The two premolars and the
      first molars of the maxilla and the mandible of all animals were extracted, and
      immediate postextraction implants were placed. After a releasing periosteal
      incision, the flap was coronally repositioned and sutured. No barrier membranes
      were used, and the only graft material used was autogenous bone chips. The
      implants were loaded after 2 months. Six months after implant loading, a block
      section was carried out, the remaining defects were filled with nonresorbable
      hydroxyapatite, and all 36 implants were retrieved. The implants were treated
      with the Precise System (Assing, Rome, Italy), to obtain thin ground sections. A
      total of three slides were cut for each implant and were examined under normal
      and polarized light. A histomorphometrical analysis was done. All implants were
      covered by compact, mature bone under examination in light microscopy. A very
      high bone-implant contact percentage (65-70%) was observed. No bone loss was
      present after the loading period. These results indicate that implants placed
      into fresh extraction sites grafted with autogenous bone chips will heal in a
      predictable way.

PMID- 11831317
TI  - Immediate placement of anatomically shaped dental implants.
AB  - Immediate placement of dental implants into tooth extraction sites is an
      effective treatment option. When immediate placement procedures are performed
      with a round implant, a void is often evident between the implant and the orifice
      of the socket. Previous treatment focused on the use of membranes or special
      closure techniques to induce bone growth into the void. Anatomically shaped
      dental implants provide a predictable alternative to previous filling techniques
      since the anatomical implants decrease or completely fill the void at the socket
      opening. This article describes a surgical technique developed for the immediate
      placement of these implants in extraction sites.

PMID- 11831319
TI  - LaminOss immediate-load implants: II. Clinical considerations of
      osteocompression.
AB  - The sinusoidal thread design of the LaminOss (Impladent Ltd, Holliswood, NY)
      osteocompressive immediate-load implant is structured with minimal shear
      interface to function in horizontal planes and stimulate bone growth by the
      action of streaming potentials at the implant thread surface area. This implant
      design, when used with a unique surgical instrumentation technique, allows
      maximum bone to be molded and compacted circumferentially around the sinusoidal
      implant threads. The surgical technique of bone lamination around larger implant
      horizontal planes (or load-bearing areas) creates a stable foundation for placing
      this implant into immediate function. For the past 10 years this surgical
      procedure has provided patients with immediate function the day of implant
      placement. The clinical advantage of immediate implant loading enhances care
      acceptance and patient satisfaction.

PMID- 11831318
TI  - LaminOss immediate-load implants: I. Introducing osteocompression in dentistry.
AB  - Osteocompression is a physiologic principle that has been clinically practiced in
      orthopedics since the early 1900s. In dentistry, controlled functional
      osteocompression is the compaction created by the tapping procedure and bone
      lamination achieved by a sinusoidal screw implant design providing physiologic
      stimulation due to streaming potentials. Functionally, there is always an applied
      force acting on bone modified by an implant design, and there is always a
      resisting force acting on the implant through the viscoelastic properties of
      trabecular structure. Through biomechanical events in bone, osseous tissue can be
      stimulated within physiologic limitations by implant design to develop along the
      lines of compressive forces dependent on the implant load-bearing area to sustain
      equilibrium. At the cellular level, these biomechanical events act on the cells
      through a phenomenon known as streaming potentials. This is an electrochemical
      potential created by the flow of extracellular fluid past a positively charged
      cell surface. Streaming potentials have a stimulating effect on osteoblasts and
      osteocytes. This stimulation under acceptable physiologic limits translates to an
      ordered deposition of osseous tissue that aids in the support of these
      compressive forces. As a sinusoidal thread design, the LaminOss osteocompressive
      immediate-load implant (Impladent Ltd, Holliswood, NY) has shown in animal
      histologic observation 2.5 times greater bone lamination achieved by the function
      of osteocompression due to the benefits of streaming potentials created by the
      LaminOss implant design. No evidence of bone necrosis was observed by any of the
      eight implants.

PMID- 11831320
TI  - Single-stage, immediate loading, and flapless surgery.
AB  - With appropriate patient selection, single-stage surgery, immediate loading, and
      flapless site preparation are dependable treatment approaches that offer
      significant benefits to implant patients. This paper briefly reviews the history
      of these approaches and describes the conditions necessary to achieve long-term
      success. Case studies also are included.

PMID- 11831321
TI  - A multidisciplinary approach to single-tooth, implant-supported prostheses: a
      report of three cases.
AB  - Dental implants and their successful long-term results have begun a new era in
      dentistry. In recent years, the increasing trend of using dental implants at
      single-tooth edentulous cases has been taken into consideration. Although
      treatment goals and objectives are similar for both prosthodontists and
      orthodontists, they rarely cooperate. Usually prosthodontists are in need of
      preprosthodontic orthodontic preparations for younger patients. In this paper,
      different preprosthodontic orthodontic procedures that may be required before the
      placement of implants at single-tooth edentulous cases are presented. In the
      first and second cases, decreased mesio-distal space was regained by different
      orthodontic treatment methods, whereas the occlusal relationship was corrected
      for better function in the third case.

PMID- 11831322
TI  - Disability claim denied: justly or unjustly?

PMID- 11831323
TI  - Whimsical historic note: stasis bandage.

PMID- 11831325
TI  - Fixed prosthodontics for the edentulous patient.
AB  - A case report is used to demonstrate the prosthetic treatment to restore a fully
      edentulous patient with fixed partial dentures. A rationale for the use of
      adequate foundations, connections, fixed prostheses, and occlusion is described
      for this patient.

PMID- 11831326
TI  - Implant periapical lesion: a clinical and histologic case report.
AB  - A new pathologic entity called implant periapical lesion has been recently
      described. This lesion could be produced by contamination of the implant surface,
      overheating of bone, overloading of the implant, presence of a pre-existing bone
      pathology, presence of residual root fragments and foreign bodies in bone,
      implant placement in an infected maxillary sinus, implant placement in a poor
      bone quality site, or lack of biocompatibility. A 49-year-old female patient
      underwent the placement of a screw-shaped titanium dental implant in the premolar
      region of the right mandible Six months after implant insertion, the patient
      presented with a persistent pain resistant to analgesics. No fistula was present
      at a clinical intraoral examination. A periapical x-ray showed the presence of a
      radiolucency at the apical portion of the implant; this image was confirmed by a
      CT Scan. The implant was removed. After implant removal, the pain disappeared
      completely. The specimen was processed to obtain thin ground sections. The
      histologic examination showed the presence of necrotic bone in the external and
      apical portion of the antirotational hole of the implant. The etiology of the
      implant failure in this instance could be related, probably, to an implant
      contamination of the apical portion of the implant.

PMID- 11831327
TI  - Evaluation of bone height and bone density by computed tomography and panoramic
      radiography for implant recipient sites.
AB  - The objective was to compare the bone height and bone density measurements of
      implant recipient sites by panoramic radiography and computed tomography. Thirty
      seven sites of 21 patients were evaluated using both panoramic radiography and
      computed tomography. The bone height was measured as the vertical distance from
      the alveolar crest to the closest anatomical landmark. Density was compared by
      means of densitometric measurements. Data was evaluated using paired t-test and
      Pearson's correlation coefficient analysis. Although bone heights measured with
      the two imaging modalities differed significantly (p < 0.05), there was a
      significant correlation between bone density measurements (r = 0.93, p = 0.0).
      Measurements of bone height as well as bone density was found to be comparable
      using either radiographic method.

PMID- 11831328
TI  - Use of a tripodal mandibular subperiosteal implant with ramus hinges for facial
      asymmetry.

PMID- 11831329
TI  - Dynamic marketing for the implant practice.

PMID- 11831330
TI  - A collective conference on the utilization of subperiosteal implants in implant
      dentistry.

PMID- 11831331
TI  - Should we look this gift horse in the mouth?

PMID- 11831333
TI  - Back to basics.

PMID- 11831334
TI  - Role of the finite element model in dental implants.
AB  - Computer-aided design and finite element methods (FEM) have interested dental
      researchers because of its use in the computer simulation and design of dental
      implants, a process greatly facilitated by the development of new computer
      technology and more accurate modeling technologies. FEM allows for a better
      understanding of stresses along the surfaces of an implant and in surrounding
      bone. This will aid in the optimization of implant design and placement of the
      implant into the bone; it will also help when designing the final prostheses to
      minimize stresses. The purpose of this review is to elucidate the role of FEM and
      the impact of this technology in clinical dentistry in the new millennium.

PMID- 11831335
TI  - Reverse torque testing and early loading failures: help or hindrance?
AB  - Reverse torque testing has been suggested to reduce the incidence of early
      loading failures during the first year of loading. However, the variables of bone
      density at stage II uncovery, the assessment of a small degree of implant
      rotation, and the effect of implant size and design have not been adequately
      evaluated. In addition, bone is weakest to shear forces, yet this is the primary
      force applied with reverse torque testing. This article reviews the benefits and
      disadvantages of reverse torque testing and suggests early crestal bone loss and
      failure of implants may be the result of this test, especially in less dense bone
      types. In addition, a nomenclature of implant failures is introduced to improve
      the correlation of information in the literature to the failure of implants in
      clinical practice.

PMID- 11831336
TI  - Soft tissue management techniques for implant dentistry: a clinical guide.
AB  - Establishing nontension primary closure over implant and bone-grafted sites
      begins with proper soft tissue management. This paper will demonstrate the
      various soft tissue flap designs required to optimize postsurgical wound healing.
      Simple and advanced flap management techniques are described in a step-by-step
      manner utilizing drawings to show each step-by-step surgical procedure.
      Management of postoperative soft tissue complications will also be addressed.

PMID- 11831337
TI  - "Jaw wars"--the next generation.

PMID- 11831338
TI  - Treatment received, treatment demand, and treatment need for temporomandibular
      disorders in 35-year-old subjects.
AB  - An epidemiological sample of 114 subjects was followed longitudinally from the
      age of 15 to 35 years with regard to treatment received, treatment demand, and
      treatment need for temporomandibular disorders (TMD). Some kind of TMD treatment
      had been provided to 18% of the subjects during the 20-year follow-up period.
      Eighty-five percent of those who had received previous TMD treatment reported
      that the treatment had had a positive effect on their symptoms. The estimated
      present need for treatment was 11%, but, in line with several other
      investigations, the active demand for such treatment was much less (3%). From age
      15 to 25 years, a small but gradual increase of clinical signs of dysfunction was
      found. From the age of 25 to 35 years, however, a significant reduction of such
      signs was noted. One explanation for this reduction of clinical signs and
      symptoms of TMD might be the stomatognathic treatment received. It was concluded
      that 18% of the subjects had received some TMD treatment during the 20-year
      follow-up period. Only 3% still had a demand for such treatment at age 35.

PMID- 11831339
TI  - Effect of arthrocentesis on TMJ disturbance of mouth closure with loud clicking:
      a preliminary study.
AB  - The objective of this study was to evaluate the short-term effect of
      arthrocentesis on temporomandibular joint disturbance of mouth closure with loud
      clicking compared to the effect of one-time pumping into the joint space previous
      to arthrography. Twenty-one consecutive patients (22 joints) with loud clicking
      during mouth closure were enrolled. All were unable to smoothly close the mouth
      without effort. Eleven patients (12 joints) were examined using magnetic
      resonance imaging (MRI) to determine disk position. They then underwent
      arthrocentesis. Ten patients (10 joints) underwent arthrography alone as
      controls. Six months later, changes in clicking and temporomandibular joint
      movement were analyzed and the disk position was re-examined. There was
      improvement of mouth closing and clicking occurred in nine joints from the
      arthrocentesis group and two joints from the control group, with a significant
      difference between the two groups. Arthrocentesis may be indicated for patients
      with temporomandibular joint dysfunction and loud clicking when mouth closing.

PMID- 11831340
TI  - Long-term outcome after treatment of temporomandibular joint osteoarthritis with
      exercise and manual therapy.
AB  - In a previous study, exercise and manual therapy demonstrated a 90% success rate
      in patients with osteoarthrosis of the temporomandibular joints in the short
      term. The aim of this follow-up study was to assess the long-term effect of these
      treatment modalities. Seventeen patients were evaluated. All patients suffered
      from osteoarthrosis of the temporomandibular joints with pain in the
      temporomandibular joint at baseline and were treated successfully in a prior
      short-term study. The parameters were pain at rest and at chewing, impairment in
      daily life, and mouth opening. At follow-up, 11 patients (65%) experienced no
      pain and 13 patients (76%) had no pain at rest (Fisher's Exact Test: p<0.02).
      Thirteen patients (76%) had a normal incisal edge clearance, and ten patients
      (59%) felt no impairment due to the disease (Fisher's Exact Test: p=0.01).
      Thirteen patients (76%), who had been treated once successfully, have not needed
      treatment within the three years after cessation of their therapy. Exercise
      therapy is an effective tool to treat osteoarthrosis of the temporomandibular
      joints.

PMID- 11831341
TI  - Comparison of moist and dry heat penetration through orofacial tissues.
AB  - Application of superficial moist heat has been shown to have a beneficial effect
      on Temporomandibular Disorder (TMD) symptoms and is often recommended for
      patients with this disorder. A review of the literature shows that few studies
      have compared the effects of moist to dry heat. Throughout this study, moist and
      dry heat were applied through a commercial heating pad alternately for 20 minute
      intervals. The application sequence was randomized and all individuals received
      both moist and dry modalities. Intraoral and extraoral thermocouples were
      positioned on the mid-cheek area of 46 volunteers to record temperature readings.
      Dry and moist heat applications were equally effective in both maximum tissue
      temperature rise and the rate of thermal transfer (p> 0.05). However, in a small
      number of subjects moist heat was preferred. As there seems to be little
      difference between using moist rather than dry heat, patients may be counseled to
      employ the superficial heating option that: 1. is an individual's personal
      preference or 2. improves convenience and optimizes compliance.

PMID- 11831343
TI  - Vertical dimension. Part 2: the changes in electrical activity of the cervical
      muscles upon varying the vertical dimension.
AB  - This study was conducted in order to determine the effect of vertical dimension
      variation on the electromyographic (EMG) activity of the sternocleidomastoid and
      trapezius muscles. The study was performed on 15 healthy subjects. Basal tonic
      electromyographic (BT-EMG) recordings were performed by placing surface
      electrodes on the left sternocleidomastoid and trapezius muscles. BT EMG activity
      was recorded upon varying the vertical dimension every five millimeters from
      vertical dimension of occlusion to 45 millimeters of jaw opening (series 1),
      following the habitual opening path. Afterward, BT-EMG activity was recorded
      every millimeter from vertical dimension of occlusion to 4 mm, and then every two
      millimeters from four to ten millimeters (series 2). In series 1, a significant
      increase of BT-EMG activity was observed in both muscles (simple logarithmic
      regression analysis). In series 2, a significant increase was observed in the
      sternocleidomastoid muscle whereas trapezius muscle did not present a significant
      change. BT-EMG behavior of the sternocleidomastoid muscle in series 2 could be
      relevant when dentists increase vertical dimension by means of intermaxillary
      appliances during a short-term period. Moreover, these results add further
      information to the concept of the interrelatedness between the different
      components of the cranio cervical-mandibular system.

PMID- 11831342
TI  - Radiographic evidence of cranial bone mobility.
AB  - The purpose of this retrospective chart review was to determine if external
      manipulation of the cranium alters selected parameters of the cranial vault and
      base that can be visualized and measured on x-ray. Twelve adult patient charts
      were randomly selected to include patients who had received cranial vault
      manipulation treatment with a pre- and post-treatment x-ray taken with the head
      in a fixed positioning device. The degree of change in angle between various
      specified cranial landmarks as visualized on x-ray was measured. The mean angle
      of change measured at the atlas was 2.58 degrees, at the mastoid was 1.66
      degrees, at the malar line was 1.25 degrees, at the sphenoid was 2.42 degrees,
      and at the temporal line was 1.75 degrees. 91.6% of patients exhibited
      differences in measurement at 3 or more sites. This study concludes that cranial
      bone mobility can be documented and measured on x-ray.

PMID- 11831344
TI  - Electromyographic activity of the jaw-closing muscles during jaw opening in
      patients with masseter muscle contracture.
AB  - Contracture of the jaw-closing muscles is one of the causes of limitation of jaw
      opening. This study examined whether there is any difference between the EMG
      activities of jaw-closing muscles during jaw opening in healthy people and in
      patients with masseter muscle contracture (MMC), who do not have a history of
      trauma or infection. The patient group consisted of eleven females, 18 to 62
      years old with no history of trauma or infections, with limited mouth opening due
      to MMC. The control group included eleven healthy females, 23 to 50 years old.
      The EMG activity was recorded bilaterally in the central portion of masseter
      muscles (Mm), the anterior portion of temporal muscles (Tm), and the anterior
      belly of digastric muscles (Dm). Nine out of the patient group showed obvious EMG
      activity in Mm during jaw opening which was different from typical EMG patterns
      during jaw opening of up to 40 mm in the control group. Among the nine patients,
      eight showed antagonistic contraction in Tm as well as Mm. The mean integral
      value of Mm and Tm during jaw opening in the patient group was significantly
      higher than in the control group (P<0.01). These results suggest that EMG
      activity during jaw opening in MMC patients with no history of trauma or
      infections is different from that in healthy people.

PMID- 11831345
TI  - Dr. David Jones refutes the Melkonians' support of the AACP application for
      craniofacial pain specialty.

PMID- 11831346
TI  - Effect of a passive jaw motion device on pain and range of motion in TMD patients
      not responding to flat plane intraoral appliances.
AB  - This study was designed to compare the effectiveness of a passive jaw motion
      device, the Therabite, and wooden tongue depressors (WTD), in patients with
      temporomandibular joint and muscle disorders, who did not improve after manual
      manipulation of the mandible and flat bite plane therapy. Forty-three patients
      were enrolled in the study and were classified as joint or muscle groups
      according to the Research Diagnostic Criteria for TMD. Twenty-four were assigned
      to the joint group, and 19 patients were assigned to the muscle group. The
      patients were assigned at random to three treatment subgroups: 1. passive jaw
      motion device therapy (Therabite); 2. wooden tongue depressors therapy (WTD); and
      3. control group. All subjects received flat bite plane appliance therapy
      throughout the treatment period. Mandibular range of motion was measured for
      maximum opening (MO), right and left lateral (Rt. Lateral, Lt. Lateral) and
      protrusive (Pr) movements. Pain level was also assessed at the beginning and at
      the end of the treatment. The results suggested that a passive jaw motion device
      is effective in increasing range of motion in both groups of temporomandibular
      disorder patients, joint (intracapsular) and muscle (extracapsular). It also
      appears to decrease pain in patients with temporomandibular disorders. Pain was
      relieved to a greater degree in the muscle group than the joint group.

PMID- 11831347
TI  - Temporomandibular joint ankylosis: a case report.
AB  - This report is based on a case of temporomandibular joint ankylosis discovered in
      a cadaver during routine student dissection in the Department of Anatomy at Tokyo
      Dental College. Extensive osseous ankylosis in the left temporomandibular joint
      was evident in this case which exhibited a distinctive bird-like facial deformity
      caused by a mandibular growth disorder. This resulted in the underdevelopment of
      the mental area in particular. Furthermore, abnormally enlarged antegonal
      notching was present along the inferior border of the mandible anterior to the
      angle. Both these manifestations indicated the likelihood that the ankylosis had
      contributed to the abnormalities and had commenced at an early stage of skeletal
      development.

PMID- 11831348
TI  - The first steps toward success for the craniofacial pain practice.

PMID- 11831349
TI  - Children's original thinking: an empirical examination of alternative measures
      derived from divergent thinking tasks.
AB  - Children's creative potential is often assessed using cognitive tests that
      require divergent thinking, such as the Torrance Tests of Creative Thinking
      (TTCT; E. P. Torrance, 1974, 1976, 1990). In this study the authors investigated
      the effect of various scoring systems on the originality index, evaluating the
      high intercorrelation of fluency and originality measures found in the TTCT
      scoring system and the applicability of TTCT scoring norms over time and across
      age groups. In 3 studies, the originality of elementary school children was
      measured using TTCT norms and various sample-specific scoring methods with the
      TTCT Unusual Uses of a Box test as well as social-problem-solving tasks. Results
      revealed an effect of scoring technique on creativity indices as well as on the
      reliability of originality scores and the relationship between originality and
      other ability measures. The usefulness of the various measures for understanding
      children's original thinking are discussed.

PMID- 11831350
TI  - Test anxiety, coping strategies, and perceived health in a group of high school
      students: a Turkish sample.
AB  - A group of high school juniors and a group of high school seniors in Izmir,
      Turkey completed measures of test anxiety, coping skills, and perceived health
      status both before and after a major exam period. Students with high test anxiety
      used less effective coping mechanisms and tended to have poorer perceptions of
      their health. Prior to the exams, juniors displayed higher test anxiety and used
      less effective coping mechanisms than seniors. After the exam periods,
      improvements were seen for both age groups on perceived health, but scores of
      younger students remained significantly higher than scores of seniors on one of
      the key measures of test anxiety. Results of the study lend support to those of
      previous studies done in other cultural contexts, and findings have implications
      for the development of interventions designed to help students cope with stress.

PMID- 11831351
TI  - The many faces of self: ego and ethnic identities.
AB  - This study addressed how adolescents come to develop a sense of ethnic identity.
      The author examined ethnic identity development as a process that occurs
      simultaneously with the development of ego identity and attitudes toward groups
      other than one's own. A multiethnic sample of 297 adolescents and young adults
      (aged 13 to 26 years) completed the Extended Objective Measure of Ego Identity
      Scale Revision 2 (EOMEIS2; L. Bennion & G. Adams, 1986), the Multigroup Ethnic
      Identity Measure (MEIM; J. Phinney, 1992), and the Other Group Orientation Scale
      (J. Phinney, 1992). An Age x Ethnic Group x Gender experimental design was used
      to determine whether these factors contributed differently to ethnic identity and
      ego identity. Analyses showed significant differences in the level of ethnic
      identity development among the ethnic groups. More pronounced age differences
      were found at the lower levels of ego identity development than at the more
      advanced levels.

PMID- 11831352
TI  - Adolescent precursors of intensity of marijuana and other illicit drug use among
      adult initiators.
AB  - This study examined (a) adolescent psychosocial risk factors for frequency
      (intensity) of marijuana use and for other illicit drug use among those who
      started using these drugs in early adulthood (adult initiators) and (b) the
      protective role of parent-adolescent relations in reducing or preventing drug use
      when adolescents enter early adulthood. The study's participants were male and
      female youth from a longitudinal prospective study. The participants' mean ages
      were 17 and 22 years at late adolescence and early adulthood, respectively.
      Independent measures assessed personality, parental, peer, and self-drug-use
      factors during late adolescence; dependent measures assessed frequency of
      marijuana use and other illicit drug use during early adulthood for initiators of
      the respective drug categories. The authors found that intensity of marijuana use
      was directly associated with the personality, parental, and self-drug-use domains
      and indirectly associated with the peer domain. Intensity of other illicit drug
      use was directly associated with personality and self-drug use. Analyses also
      revealed that some parent-adolescent relations factors buffered the effects of
      risk factors for both marijuana and other illicit drug-use intensity, whereas
      others enhanced the effects of protective factors against other illicit drug-use
      intensity. The results indicate that there are both commonalities and differences
      in precursors of marijuana and other illicit drug-use intensity among initiators
      of these drugs during early adulthood.

PMID- 11831353
TI  - Preschoolers' use of reflective properties: identification of reflections on
      partially transparent surfaces.
AB  - This exploratory study extended past studies of children's ability to reference
      the mirror as a tool in locating the source of reflected images to preschoolers'
      ability to use the affordances of a transparency. Thirty-six children (3.5 to 5
      years old) were shown nonreflected lights and lights reflected on a partially
      transparent, glassy surface. Children did not spontaneously locate the source of
      the reflected image. However, they were able to verbally discriminate reflected
      from nonreflected images following training. These findings indicate that,
      although preschoolers may not spontaneously use transparencies as a perceptual
      tool, the ability to distinguish visual differences of reflected from
      nonreflected images on transparencies is likely within preschool children's
      developmental capacity.

PMID- 11831354
TI  - Father postdivorce well-being: an exploratory model.
AB  - The purpose of this study was to test a theoretical model of the psychological
      well-being of fathers following divorce. The theory postulated that father
      postdivorce well-being was related to father role clarity, role satisfaction,
      age, income, education level, custody arrangement, encouragement from others,
      time since divorce, and involvement in an intimate relationship following
      divorce. Participants were 94 fathers from a midwestern city who completed self
      administered questionnaires. Data were assessed using path analytic techniques.
      Involvement in an intimate relationship was found to have the greatest influence
      on father postdivorce well-being. Role satisfaction had direct effects on father
      postdivorce well-being and was important as a mediating variable for 4 constructs
      within the model. The findings suggest that father well-being following divorce
      is a complex phenomenon, influenced by all of the model variables except income,
      education level, and time since divorce. Implications for preventive intervention
      strategies, based on risk factors identified in this study, and suggestions for
      further research are discussed.

PMID- 11831355
TI  - Parents' expressiveness and young children's emotion decoding with parents and
      unknown adults.
AB  - The authors investigated young children's ability to decode the emotions of
      happiness and anger expressed by their parent and an adult stranger. Parents and
      adult strangers (encoders) were videotaped while describing events that had
      elicited happiness or anger. Children viewed brief clips edited from these
      videotapes and indicated the emotion that their parent or the stranger was
      expressing. With male encoders, only children's age predicted accuracy. With
      female encoders, mothers' expressive style and children's age interacted to
      predict children's decoding accuracy. Compared with older children of less
      positively expressive mothers, older children of more positively expressive
      mothers were more accurate overall, because they were better at recognizing
      happiness. In general, children were no more or less accurate in decoding their
      parent's emotions than they were in decoding an unknown adult's emotions.

PMID- 11831356
TI  - Foundations of educational psychology: Howard Gardner's neoclassical psyche.
AB  - This article is a theoretical examination of the implications of Howard Gardner's
      work in developmental and educational psychology (1983, 1993, 1999a, 1999b) for
      the structure of the psyche. The author accepts as axiomatic, in the context of
      this article, Gardner's educational manifesto (1999a) that all students should be
      taught disciplinary understandings of truth, beauty, and goodness. Rational
      inferences are then made indicating that the psyche that Gardner intends to
      educate and help develop is in the form of a neoclassical psyche and that it is
      structured by the capacities to know truth, to love beauty, and to will goodness.

PMID- 11831357
TI  - Ras/MAP kinase pathway is associated with the control of myotube formation but
      not myofibril assembly in quail myoblasts transformed with Rous sarcoma virus.
AB  - Tyrosine kinase activity of v-Src from Rous sarcoma virus (RSV) inhibits the
      differentiation of quail myoblasts. To clarify the inhibitory mechanism, we
      focused on the signaling pathways from v-Src. When the activation of the Ras/MAP
      (mitogen-activated protein) kinase pathway was inhibited by a dominant-negative
      mutant of Ras or PD98059, a specific inhibitor of p42 MAP kinase kinase,
      differentiation was restored; muscle specific proteins were expressed and
      myotubes formed even under active conditions of v-Src. Wortmannin, a specific
      inhibitor of phosphatidylinositol 3-kinase (P13-kinase), showed no effects on the
      inhibition by v-Src. These findings suggest that v-Src activates the Ras/MAP
      kinase signaling pathway, but not the P13-kinase pathway, and inhibits the
      differentiation. However, the myotubes derived from the dominant-negative Ras did
      not form actin fibers, suggesting that myofibril assembly is regulated by other
      pathway(s) from v-Src.

PMID- 11831358
TI  - Temperature dependence in proliferation of tetraploid Meth-A cells in comparison
      with the parent diploid cells.
AB  - The temperature dependency for the growth of tetraploid Meth-A cells established
      from diploid cells was examined in comparison with the parent diploid cells.
      Proliferation of the tetraploid cells was markedly suppressed below 35 degrees C.
      At above 40 degrees C, both the diploid and tetraploid Meth-A cells ceased
      growing. Flow cytometry (FCM) analysis showed that the hyperploid cell fraction
      increased in the tetraploid Meth-A cell population at low temperatures. The
      fluidity of cell membranes at different temperatures was measured by means of
      electron spin resonance (ESR), and it was almost the same between the diploid and
      tetraploid Meth-A cells. It was suggested that the decreased proliferation below
      35 degrees C of the tetraploid Meth-A cells might be due to the increased volume
      of the cells.

PMID- 11831359
TI  - Identification of the core protein carrying the Tn antigen in mouse brain:
      specific expression on syndecan-3.
AB  - We isolated glycoproteins carrying the Tn antigen, which was expressed
      spatiotemporally in the developing mouse brain. The Tn antigen was expressed on
      two molecular species with a molecular weight from 200 to 350 kDa and 110 to 160
      kDa, as judged on SDS-PAGE. Although the two glycoproteins showed different
      susceptibilities to heparitinase I and solubilities in a salt solution, after
      treatment with V8 protease they showed the same mobility corresponding to a
      molecular weight of 90 kDa on SDS-PAGE, suggesting that these two molecules
      shared a common core protein. Partial N-terminal sequences of the glycoproteins
      were determined, i.e. AQRXRNENFERPV and ALAAPXAPAMLP, which were identified as
      the sequences of the N-terminal and central portions of syndecan-3, respectively.
      Both glycoproteins were reactive to anti-mouse syndecan-3 antibody. These results
      suggest that one is a soluble syndecan-3 cleaved between mucin-like domain and
      transmembrane domain, and the other is a membrane-bound syndecan-3 lacking N
      terminal glycosaminoglycan attachment sites, and that both glycoproteins have a
      mucin-like domain characteristic of syndecan-3, in which the Tn antigen may be
      expressed.

PMID- 11831360
TI  - Enhancement of diphtheria toxin-induced apoptosis in Vero cells by combination
      treatment with brefeldin A and okadaic acid.
AB  - In the present study, we compared the abilities of ricin and diphtheria toxin to
      induce apoptosis in Vero cells. The cytolysis and DNA fragmentation by ricin
      paralleled its protein synthesis inhibitory activity. However, unlike ricin,
      diphtheria toxin could induce neither cytolysis nor DNA fragmentation in Vero
      cells up to very high concentration, in spite of the fact that Vero cells were
      even more sensitive to protein synthesis inhibition by diphtheria toxin than
      ricin. Interestingly, coexistence of brefeldin A (BFA) and okadaic acid (OA)
      significantly enhanced diphtheria toxin-mediated cytolysis and DNA fragmentation
      without affecting the activity of protein synthesis inhibition. Ammonium chloride
      almost completely abolished the ability of diphtheria toxin to induce apoptosis
      in the presence of BFA and OA as well as the protein synthesis inhibitory
      activity. The mutant CRM 197, which does not catalyze the ADP ribosylation of
      elongation factor-2 (EF-2), failed to induce apoptosis in Vero cells even in the
      presence of BFA and OA. Thus, translocation of diphtheria toxin into the cytosol
      and subsequent enzymatic inactivation of EF-2 may be necessary steps to induce
      apoptosis. Taken together our results suggest that protein synthesis inhibition
      by toxins is not sufficient to induce apoptosis, and underlying mechanisms of
      apoptosis induction may be distinct between ricin and diphtheria toxin. Since a
      morphological change in the Golgi complex was observed in Vero cells treated with
      BFA and OA, modulation of the Golgi complex by these reagents may be partly
      responsible for enhanced apoptosis induction by diphtheria toxin.

PMID- 11831361
TI  - Type V collagen distribution in liver is reconstructed in coculture system of
      hepatocytes and stellate cells; the possible functions of type V collagen in
      liver under normal and pathological conditions.
AB  - The contents of type I, type III and type V collagen and the collagen type
      specific distributions in liver under normal and cirrhotic conditions were
      examined. In CCl4 injected rat, the increasing amount of type V collagen was a
      specific event during the progression of cirrhosis. In normal liver,
      immunohistochemical observation showed that type V collagen was localized on the
      fine fibrils, while type I was localized on the thick fibril. Type V collagen was
      partially colocalized with type IV collagen. In the cirrhotic liver, type V
      collagen was localized on the margin of the thick fibrous septa along with type
      IV collagen. Type I collagen existed in the core region of fibrous septa where
      the stellate cells were prominent. To elucidate the mechanism of the type
      specific deposition of collagen in the liver, we constructed a coculture system
      using both stellate cells and hepatocytes. In this system, type V collagen was
      mainly deposited on hepatocyte colonies not on stellate cells, while type I
      collagen fibrils were localized on stellate cells. The spatial positioning of
      type I and type V collagens in vitro was similar to that in the liver. In the
      cell adhesion assay, the adhesion of stellate cells to type V collagen was poorer
      than that of the hepatocytes. The collagen type-specific affinity of the stellate
      cells and hepatocytes may explain the specific localization of type V collagen in
      the liver and coculture system. These results suggested that the functions of
      type V collagen are not only to connect type IV collagen with type I collagen
      fibril, but also to protect the parenchyma from excess type I collagen deposition
      produced by stellate cells under pathological conditions.

PMID- 11831362
TI  - Drosophila bipectinata species complex.
AB  - The Drosophila bipectinata species complex belongs to the ananassae subgroup of
      the melanogaster species group (Genus Drosophila, Subgenus Sophophora). The
      members of the complex are: D. bipectinata, D. parabipectinata, D. malerkotliana,
      and D. pseudoananassae. Of the four species, D. bipectinata is most widely
      distributed. Females are indistinguishable, but males are distinguishable by
      their sex-comb teeth number and pattern and by abdominal colouration. Chromosomal
      inversions have been detected in these species. In natural populations of D.
      bipectinata the frequency of inversions and the level of inversion heterozygosity
      were found to be very low but in laboratory stocks inversions persisted for more
      than 20 generations due to heterotic buffering. On an average 9.3 fixed
      interspecific inversions separate each species pair. Non-random association
      between linked inversions indicated epistatic interaction in natural populations
      of D. bipectinata. Certain spontaneous mutations were detected and mapped for the
      first time in D. bipectinata. Low frequency of spontaneous male recombination has
      also been reported in D. bipectinata. Sexual isolation study in the complex
      indicated strong preference for homogamic mating. The results also indicated
      incomplete sexual isolation among different members of this complex. The
      isolation estimate among six different geographic populations of D. bipectinata
      ranged from 0.54 - 0.92 representing positive assortative mating which is an
      evidence for incipient sexual isolation. Incipient sexual isolation was also
      found within D. malerkotliana and D. parabipectinata . Chromosomal, hybridization
      and allozyme studies revealed close phylogenetic relationship among the four
      species of the bipectinata complex. Mitochondrial DNA study revealed net
      nucleotide difference (delta) between these species to be very small (0.0002 +/-
      0.0008) reflecting closeness. Evidence for genetic control of sexual activity and
      existence of sexual selection in D. bipectinata has been shown on the basis of
      mating propensity tests carried out on geographic strains, their hybrids and
      diallel crosses. Significant variation was found among the strains tested with
      respect to courtship time, duration of copulation and fertility. A positive
      correlation between duration of copulation and fertility in D. bipectinata was
      found. Evidence for rare-male mating advantage was also found in D. bipectinata.
      A positive response to selection for high and low mating activity provided
      evidence for polygenic control of this phenomenon in D. bipectinata. Bilateral
      outgrowths on thorax, a unique phenotype, reported for the first time in D.
      bipectinata has been shown to affect mate recognition ability. Results of the
      study on pupation site preference (larval behaviour) and oviposition site
      preference (non-sexual behaviour) have also been included.

PMID- 11831363
TI  - Effect of metanil yellow and malachite green on DNA synthesis in N
      nitrosodiethylamine induced preneoplastic rat livers.
AB  - Metanil yellow (MY) and malachite green (MG) are textile dyes, which, despite the
      ban occurs unsrupulously as food colouring agents. Accordingly they constitute a
      serious public health hazard and are of sufficient environmental concern. We have
      earlier reported that both MY and MG have tumor enhancing effects on the
      development of hepatic preneoplastic lesions induced by N-nitrosodiethylamine in
      rats. In order to understand the possible mechanisms by which MY and MG enhance
      tumor development, in this study we have tested the effects of MY and MG on DNA
      synthesis and PCNA expression in preneoplastic hepatic lesions during N
      nitrosodiethylamine (DEN) induced hepatocarcinogenesis in male Wistar (WR) rats.
      Rats were administered 200 ppm DEN through drinking water for a period of one
      month. Administration of DEN for a period of one month showed an upregulation of
      cell cycle regulatory proteins namely cyclin D1, CDK4, cyclin E and CDK2.
      Accordingly, in other experiments, the animals were further administered MY and
      MG for a period of one month following one month DEN treatment. The effects of MY
      and MG were monitored on the basis of cell proliferation markers--DNA synthesis
      and PCNA expression both by immunohistochemical and immunoblotting. Following DEN
      administration, MY, MG and PB showed stimulation of DNA synthesis and increased
      PCNA expression when compared with either the corresponding controls or only DEN
      treated animals. In the present study, enhancing effect of MY, MG and PB on the
      cell proliferation markers during DEN-induced hepatic preneoplasia in rats was
      observed.

PMID- 11831364
TI  - Effect of environmental deprivation on anxiety in rats.
AB  - Environmental deprivation (ED) induced a significant increase in open-field
      ambulation, rears, self-groomings, faecal pellets and decrease in activity in
      centre in Charles Foster albino rats of 30, 45 and 60 days age groups. In
      elevated plus maze, significant attenuation of open arm time/entries and
      augmentation of enclosed arm time/entries were noted in ED rats of all the three
      age groups. Similarly ED rats also showed significant decrease in time spent on
      open arms, entries, head dips and stretched attend postures in comparison to age
      matched rats reared under normal environmental conditions. The results indicate
      that imposition of environmental deprivation in rats' life consistently resulted
      in significant anxiogenic behaviour on all the tests. However, the anxiogenic
      effect of ED was less marked when it was imposed at 60th day of life in rats.

PMID- 11831365
TI  - In vivo radioprotective effect of Moringa oleifera leaves.
AB  - Radioprotective property of Moringa oleifera leaves was investigated in healthy
      adult Swiss albino mice. Animals were injected (ip) with 150 mg/kg body weight of
      50% methanolic extract (ME) of M. oleifera leaves, as a single dose, or in 5
      daily fractions of 30 mg/kg each, and exposed to whole body gamma irradiation
      (RT, 4 Gy) 1 hr later. Five animals from each group were sacrificed at 1, 2 and 7
      days after treatment. Bone marrow protection was studied by scoring aberrations
      in metaphase chromosomes and micronucleus induction in polychromatic erythrocytes
      and normochromatic erythrocytes. Pretreatment with a single dose of 150 mg/kg ME
      significantly reduced the percent aberrant cells to 2/3rd that of RT alone group
      on day 1 and brought the values to normal range by day 7 post-irradiation. A
      similar effect was also seen for the micronucleated cells. Fractionated
      administration of ME (30 mg/kg x 5) gave a higher protection than that given by
      the same dose administered as a single treatment. ME also inhibited the Fenton
      reaction-generated free radical activity in vitro in a concentration dependent
      manner. These results demonstrate that pretreatment with the methanolic leaf
      extract of M. oleifera confers significant radiation protection to the bone
      marrow chromosomes in mice and this may lead to the higher 30 day survival after
      lethal whole body irradiation.

PMID- 11831366
TI  - Effect of chronic treatment with Bis(maltolato)oxovanadium (IV) in rat model of
      non-insulin-dependent-diabetes.
AB  - Effect of chronic treatment with Bis(maltolato)oxovanadium (IV) (BMOV) was
      studied in streptozotocin (STZ)-induced neonatal non-insulin-dependent-diabetic
      (NIDDM) rats. Intraperitoneal injection of STZ (90 mg kg(-1)) in Wistar rat pups
      (day 2 old) produced mild hyperglycemia, impaired glucose tolerance and insulin
      resistance at the age of 3 months. Treatment with BMOV (0.23 mM kg(-1)) in
      drinking water for 6 weeks produced a significant decrease in elevated serum
      glucose levels without any significant change in serum insulin levels in diabetic
      rats. BMOV treatment significantly decreased integrated area under the glucose
      curve without any significant change in integrated area under the insulin curve
      indicating improved glucose tolerance. Treatment also significantly increased
      K(ITT) value of diabetic rats indicating increased insulin sensitivity. BMOV
      treatment significantly reduced hypercholesterolemia in diabetic rats. Treatment
      also significantly decreased serum triglyceride levels in both diabetic and non
      diabetic rats. The data suggest that chronic BMOV treatment improves glucose and
      lipid homeostasis. These effects appear to be due to the insulin sensitizing
      action of vanadium.

PMID- 11831367
TI  - Antiallergic/antiasthmatic effect of novel antiallergic hexapeptide-95/220 in
      various experimental models.
AB  - The effects of newly synthesized antiallergic hexapeptide 95/220 was investigated
      on various allergic and asthmatic test models. This newly developed peptide was
      found to be more potent than clinically used drug disodium cromoglycate (DSCG).
      Hexapeptide 95/220 inhibited immediate hypersensitivity reactions such as passive
      cutaneous anaphylaxis (PCA) and mast cell degranulation in rats, antigen-induced
      bronchoconstriction in actively sensitized guinea pigs in dose dependent manner
      like DSCG. Antigen-induced contraction of guinea pig ileum was also markedly
      inhibited by this newly developed hexapeptide in the same fashion as ketotifen
      and DSCG did but at comparatively lower dose. Egg albumin-induced histamine
      release was also blocked by this hexapeptide from chopped lung tissues of
      sensitized guinea pigs. These results suggest that hexapeptide' 95/220 has potent
      inhibitory effect on immediate hypersensitivity reactions thereby inhibiting
      mediator release from mast cell. Moreover, this newly synthesized peptide is
      orally active and effective at lower doses as compared to standard drugs.

PMID- 11831369
TI  - Effect of amniotic sac puncture on parturition in rat.
AB  - Pregnant Charles Foster rats were subjected to amniotic sac puncture on day 15 of
      gestation and the effect was observed on parturition. All the control rats as
      expected delivered on day 22 of gestation. In the group where all the sacs were
      punctured, only 12.5% rats delivered on day 22 while rest either failed to
      deliver (62.5%) or died (25%). In the group with unpunctured sacs at vaginal
      ends, 75% rats delivered on day 21 while 25% on day 22. In the group with
      unpunctured sacs at ovarian ends, 75% rats delivered on day 23 and rest 25%
      failed to deliver. The resorption rates ranged between 61 to 94% in different
      groups. Malformations were observed only in one pup. The results suggest that
      amniotic sac puncture interferes with parturition in the form of either failure
      or delayed parturition. Nonpatency of the birth canal due to puncture induced
      fetal deaths and tissue adhesions were presumed to be the contributing factors.

PMID- 11831368
TI  - Effect of immunization with lipid associated polysaccharide antigen and anti CD-2
      antibodies on class II MHC expression and cellular immune response in BALB/C mice
      infected with Leishmania donovani.
AB  - In a bid to characterize the antigens and immunization mechanisms which may be
      used to produce a protective response against L. donovani, role of lipid
      associated polysaccharide (LPS) antigen and whole antigen was evaluated. BALB/C
      mice were immunized with whole or LPS antigen in combination with one of three
      putative adjuvents (anti CD-2 antibody/FIA/0.85% Saline). LPS antigen emulsified
      in anti CD-2 antibody was found to induce significant antibodies in mice on day
      28 against challenge with lethal dose of L. donovani. Immunoprophylactic
      properties of LPS and whole antigen was investigated on day 40 through cytokine
      elicitation (IL-2), MIF) in culture supernatants of spleen cells, but before that
      MHC-II expressed on macrophage was studied. The LPS antigen in combination with
      anti CD-2 antibody was found to be most immuno-reactive inducing higher MHC-II
      expression on macrophages which was associated with substantial rise in the level
      of MIF and IL-2. It coincided with decline in antibody titre in 100% mice
      immunized with LPS antigen while Leishmania injected as whole antigen failed to
      induce specific macrophage and T-cell response with all the above formulations.
      We surmise from our data that lipid associated polysaccharide antigen linked to
      anti CD-2 antibody has potential for eliciting protective immunity against
      Leishmania.

PMID- 11831370
TI  - Rat cheek gland compounds: behavioural response to identified compounds.
AB  - Cheek gland secretions from sexually mature and reproductively active male and
      female laboratory rats (Wister strain), Rattus norvegicus albinus were analysed
      by gas chromatography/mass spectroscopy. Alkanes, aliphatic acids esters and
      alcohols were identified in the secretions. Cheek gland preparation from males
      contained predominantly three compounds, viz. di-n-octyl phthalate (I); 1,2
      benzene diacarboxylic acid butyl (2-ethyl hexyl) ester (II); and 1,2 benzene
      dicarboxylic acid (2-methylpropyl) ester (III) whereas in the cheek gland of
      females two compounds, viz, 1,2-benzene dicarboxylic acid (2-methylpropyl) ester
      (I); and 2,6,10 dedecatrien-1-ol, 3,7,11-trimethyl-(Z, E) (II) were the major
      fractions. The identified compounds were tested for odour preferences. Compounds
      II and III of males and I and II of females attracted both male and female
      conspecifics. By contrast, compound I from males only attracted females. The
      level of attraction also varied from compound to compound. The results suggest
      that cheek gland secretions have pheromonal functions.

PMID- 11831371
TI  - Evaluation of safety and efficacy of a gold containing Ayurvedic drug.
AB  - Gold containing Ayurvedic preparation, Swarna Vasant Malti, was given to 20 male
      persons in a dose of 100 mg twice a day for 40 days under supervision of
      Ayurvedic physicians. The total cumulative intake of 160 mg of gold at the rate
      of 4 mg per day in this form did not have any toxic effect on human body as
      evidenced by clinical examination, unaltered body weight, absence of urinary
      pathology and by 30 sensitive biochemical and enzymatic tests. The gold from this
      Ayurvedic preparation was found in plasma and erythrocytes, excreted partly in
      urine and was present in semen. Gold binding to albumin and hemoglobin slightly
      increased their electrophoretic mobility towards anode. This gold preparation
      seemed to increase sperm motility and prostatic activity.

PMID- 11831372
TI  - Characterization of genetic diversity of some serovars of Bacillus thuringiensis
      by RAPD.
AB  - RAPD based fingerprinting of 21 serovars of Bacillus thuringiensis (Bt)
      representing different serotypes was performed using 19 random decamer primers. A
      total of 172 polymorphic fragments, ranging in size from 161-2789 bp, were
      amplified from 13 of the 19 primers. Pairwise genetic similarity analysis
      revealed very low similarity values, ranging from 3-68%, among the serovars of
      Bt, indicating high genetic divergence. Nineteen serovars of Bt fell in two major
      clusters and remaining two formed solitary clusters in the dendogram. Clustering
      of Bt strains established genetic relatedness between serovars and serotypes. It
      has been suggested that RAPD analysis can be used for genotypic characterization
      of Bt to complement flagellar serotyping.

PMID- 11831373
TI  - Sustained release implants of chloroquine phosphate for possible use in
      chemoprophylaxis of malaria.
AB  - Implants of chloroquine phosphate (CQP) using biodegradable polymer, gelatin (G)
      and cross-linked gelatin (CLG) were prepared and evaluated to assess their
      physicochemical properties and in vitro release profile. The mechanism and
      kinetics of release were studied to correlate the release phenomenon with the
      formulation parameters. Out of many batches of the implants investigated, the
      implant prepared with 20% gelatin at 2:1 drug polymer ratio, 10% crosslinking
      agent and 2% plasticizer (Batch J) was found to provide optimum release behavior
      conforming to the requirements of a long term implant for a week. In vivo studies
      conducted on albino rats showed consistent therapeutic blood level over a period
      of 7 days. Mean residence time (MRT) of the drug released in the body, calculated
      as the ratio of the area under the first moment curve (AUMC) to area under
      concentration time curve (AUC) was 72 hr for implant against 2.42 hr for
      subcutaneous injection.

PMID- 11831374
TI  - Rapid extraction of DNA from diverse soils by guanidine thiocyanate method.
AB  - Molecular methods are being frequently used for the study of soil microbial
      communities as majority of naturally occurring microbial populations are non
      culturable. In the present study, we describe a protocol of DNA extraction from
      diverse soils using a combination of heat, enzyme (lysozyme) and guanidine
      thiocyanate. The efficacy of the procedure was evaluated in terms of yield,
      purity and duration of extraction. The protocol was effective for neutral, acidic
      as well as alkaline soils (pH range 4.5-8.5). The extracted soil DNA was observed
      with negligible shearing on agarose gel and the time taken for restriction
      digestion was very less. Further, the DNA extracted was almost completely devoid
      of contaminants and pure enough which could be used for PCR amplification and
      Southern hybridization.

PMID- 11831375
TI  - Interspecific hybridization in Brassica juncea and Brassica tournefortii through
      embryo rescue and their evaluation for biotic and abiotic stress tolerance.
AB  - Interspecific hybrids were obtained in an otherwise incompatible cross Brassica
      juncea x Brassica tournefortii through in vitro culture of hybrid embryos. The
      best response was observed from culture of embryos excised 20 days after
      pollination on MS medium supplemented with kinetin, alpha-naphthylacetic acid,
      gibberellic acid, glutamine and casein hydrolysate. One hybrid plant had many
      distinct or intermediate characters. It was tolerant to aphid attack, exhibited
      irregularities in meiotic events and was partially fertile. The F2 open
      pollinated and BC1 progenies showed a large diversity in their morphological
      traits and some promising plants with less aphid infection, drought tolerance and
      high yield were selected.

PMID- 11831376
TI  - In vitro high frequency regeneration of plantlets of Vigna mungo and their ex
      vitro growth.
AB  - Of the five explants of V. mungo var. T9 used, the excised shoot tips gave best
      response with regard to offshoot formation followed by the embryonal axis
      explants. While a treatment comprising 0.5 mgL(-1) BAP, 0.5 mgL(-1) 2iP and 0.1
      mgL(-1) NAA induced differentiation of an average 10 offshoots in shoot tip
      explants, only 3 offshoots were formed in the explants of embryonal axis in a
      treatment containing 0.5 mgL(-1) BAP and 0.1 mgL(-1) NAA, found optimum for them.
      Multiple shoots differentiated when explants with earlier regenerated and growing
      offshoots were first cultured in a treatment containing 0.1 mgL(-1) BAP, 0.25
      mgL(-1) IAA and 5 mgL(-1) CCC and then subcultured in the same treatment but
      having only 1 mgL(-1) CCC. The isolated shoots rooted in 0.5 mgL(-1) IAA resulted
      in the formation of complete plantlets of an average height of 15 cm in 20 days.
      The in vitro-regenerated plants grew normally under field conditions and came to
      flowering as well.

PMID- 11831377
TI  - Spermatotoxic effect of carbendazim.
AB  - Carbendazim, suspended in sunflower oil, was administered to Wistar male rats
      through an oral intubation at a daily dose of 25 mg/kg body weight for 48 days,
      and the cauda epididymal sperm were analysed on day 49 for counts, motility and
      abnormalities. The study indicates that carbendazim affects the cauda epididymal
      sperm as seen in decreased sperm counts, inhibition of motility and increased
      incidence of abnormalities.

PMID- 11831378
TI  - Biochemical studies on hypoglycemic effect of Aavirai kudineer: a herbal
      formulation in alloxan diabetic rats.
AB  - Aavirai Kudineer (AK) is an herbal decoction of seven botanical drugs, cited in
      the Gunapadam; a Tamil Siddha medical text. The anti-diabetic efficacy of this
      formulation was evaluated using alloxan-induced diabetic and normal rats. Glucose
      tolerance was observed within 1 hr in AK-treated rats (10 ml/kg body ) as
      compared to control. A significant decrease in the severe hyperglycemia
      characteristic of alloxan diabetes was noted after 15 days of AK treatment.
      Further AK treatment reversed the elevated urea, creatinine, cholesterol and
      decreased protein values to near normal levels. Assay of glycogen content and
      chief carbohydrate-metabolizing enzymes, viz. hexokinase, glucose-6-phosphatase
      and fructose 1,6 diphosphatase in the liver of diabetic and AK-treated diabetic
      rats clearly ascertains the hypoglycemic efficacy of this formulation. The mode
      of action of this herbal formulation remains to be elucidated.

PMID- 11831379
TI  - Experimental evidence for a non-renin mediated pathway during TAME-esterase
      induced contractions in rat aorta in vitro.
AB  - Possible pharmacological effects of N-alpha-tosyl L-arginine methyl ester [TAME]
      were studied on rat aorta strips in vitro. Results showed that [TAME]-esterase
      was an endothelium dependent component that involved a nitric oxide cyclic-GMP
      mediated pathway. Furthermore, during activation of Kinin-Kallikrein system, TAME
      esterase induced contractions involve degradation of kinins by kininases.

PMID- 11831380
TI  - Effect of androgens on oviductal growth in skipper frog Rana cyanophlyctis.
AB  - Effects of exogenous androgens (testosterone, testosterone propionate and
      dihydrotestosterone) and estradiol-17beta on the oviductal growth/hypertrophy
      were studied in young and bilaterally ovariectomized (BLO) adult frogs (Rana
      cyanophlyctis) during postbreeding phase of the reproductive cycle. Estradiol
      17beta injections induced oviductal hypertrophy to the maximal extent among
      hormone treated groups. In androgen treated frogs also there was an increase in
      the oviductal dry weight and protein content both in young and BLO adult frogs,
      suggesting the role of endogenous androgens in controlling the growth of oviduct
      in R. cyanophlyctis.

PMID- 11831381
TI  - Primary cell culture from fish gills and kidney using fish serum.
AB  - A novel, cost effective and time saving technique for primary cell culture from
      gills and kidney using fish serum has been developed. Single cell suspension of
      gills and kidney of Clarias gariepinus was obtained by trypsinization. Minimum
      essential medium supplemented with 10% fish serum in place of 10% foetal calf
      serum and 20% fish muscle extract, yielded confluent monolayer on 6th and 8th day
      in gill and kidney tissue respectively at 28 degrees C. Fish serum can be
      successfully used as media supplement for cultivation and maintenance of primary
      cell culture from fishes.

PMID- 11831382
TI  - Effect of probiotics on bacterial population and health status of shrimp in
      culture pond ecosystem.
AB  - The artificially manufactured probiotics having beneficial bacteria, Bacillus
      spp. was applied regularly in a modified extensive shrimp (Penaeus monodon)
      culture pond, located on the bank of Vellar estuary, Parangipettai. The
      populations of total heterotrophic bacteria (THB), beneficial bacteria (Bacillus
      spp.) and pathogenic bacteria (vibrios) were monitored in water and sediment of
      the pond. The results were compared with a control pond, situated in the same
      location having same water spread area, stocking density, species managed with
      same technologies and optimum environmental parameters in which no probiotic was
      applied. The populations of THB and Bacillus spp. in the experimental pond
      increased and the vibrios decreased after each application of probiotics. But the
      result of the control pond showed an increasing trend of the populations of THB,
      Bacillus spp. and vibrios towards days of culture. The control pond had lower
      levels of THB and Bacillus spp. and higher levels of vibrios than the probiotic
      applied (experimental) pond. Also the probiotics maintained optimum transparency
      and low organic load in the experimental pond as compared to control. In general,
      water and sediment had almost equal number of Bacillus spp. and vibrios, but
      sediment had higher THB load than water. The applications of probiotics lesser
      pathogenic vibrios and enhance beneficial bacilli in the culture leading to
      improved water quality, promoted growth and survival rates and increased the
      health status of the shrimp without stress and disease outbreaks. Thus the
      application of probiotics could lead to disease-free and profitable shrimp
      culture operations which will be helpful for shrimp farmers as most of them are
      now-a-days severely affected by microbial diseases.

PMID- 11831383
TI  - Somatic embryogenesis and plant regeneration in Gloriosa L.
AB  - Friable callus was initiated from shoot apices of Gloriosa superba L. on basal MS
      medium supplemented with 2, 4-D (4mg L(-1)) + Kn(5 mg L(-1)) + CH(10 mg L(-1)) +
      CW(20%). Subculture of callus on the same medium after 4-5 weeks showed induction
      of large number of somatic embryos, which was confirmed with histological
      studies. Development of embryoids in plantlet took place when the embryogenic
      callus was transferred to basal MS medium supplemented with BAP (5 mg L(-1)),
      CH(50 mg L(-1)) +CW(20%). Roots were developed by subculturing them on to the
      medium containing Kn or BAP (5 mg L(-1)) and IBA (4 mg L(-1)). Plantlets were
      successfully transferred to pots containing mixture of soil, sand and farmyard
      manure (2:1:1).

PMID- 11831384
TI  - In vitro regeneration of Hypericum patulum Thunb.--a medicinal plant.
AB  - A protocol was developed for high frequency plant regeneration in H. patulum by
      shoot-tip culture. H. patulum plants were collected from a wild source growing at
      high altitude in the eastern Himalayas. Multiple buds were initiated from shoot
      tips cultured on Murashige and Skoog's medium supplemented with BAP, kinetin.
      Addition of thiamin HCI, Ca-pantothenate and biotin enhanced multiple shoot
      formation. Upon transfer to phytohormone free liquid medium following a brief
      exposure to auxin, root formation occurred from the micro shoots . Rooted plants
      were hardened and transferred to soil. Regeneration potentiality was found to be
      constant throughout the year in long term cultures.

PMID- 11831385
TI  - Advances DNA vaccines.
AB  - Extraordinary advances in biotechnology make DNA vaccines the most promising area
      of vaccinology. This article reviews the public health impact of vaccines in the
      20th century, summarizes immunologic concepts, and updates the status of DNA
      vaccine development and its impact on clinical practice.

PMID- 11831386
TI  - Mrnp41 (Rae 1p) associates with microtubules in HeLa cells and in neurons.
AB  - Mrnp41 (hRae1p) is an evolutionarily highly conserved protein, which is a
      potential component of mRNP particles and plays a role in nuclear mRNA export.
      The protein is mainly localized at the nuclear pore complex, but is also
      associated with distinct nuclear domains and with a meshwork of numerous small
      particles in the cytoplasm (Kraemer and Blobel (1997): Proc. Natl. Acad. Sci. USA
      91, 1519-1523). We show that the cytoplasmic pattern of mrnp41 is sensitive to
      treatment with the microtubule (MT)-depolymerizing drug nocodazole which causes
      disappearance of mrnp41 from the cell periphery and concentration around the
      nucleus. By immunofluorescence we demonstrate that mrnp41 colocalizes with MT in
      HeLa cells and displays an MT-like distribution in cultured neurons. Association
      of mrnp41 with MT is further demonstrated by copurification with MT from pig
      brain throughout several steps of polymerization and depolymerization. Separation
      of MT-associated proteins (MAPs) by phosphocellulose (PC) chromatography showed
      copurification of mrnp41 with MAPs. These data show an association of mrnp41 with
      MT and, moreover, demonstrate that an intact MT system is necessary for
      dispersion of mrnp41-containing particles to the cellular periphery. The
      essential role of mrnp41 in spindle pole separation and cell cycle progression
      may also be related to its ability to bind to MTs.

PMID- 11831387
TI  - AlphaB-crystallin phosphorylated at Ser-59 is localized in centrosomes and
      midbodies during mitosis.
AB  - We have reported that the three serine residues in alphaB-crystallin are
      phosphorylated under various stress conditions. We prepared affinity-purified
      antibodies recognizing each of the phosphorylated serine residues (Ser-19, Ser
      45, and Ser-59, respectively) in alphaB-crystallin with peptides (p19S, p45S, or
      p59S) that contained the corresponding phosphorylated serine residue.
      Immunocytochemically anti-p45S antibodies stained the cytoplasm of mitotic cells
      (J. Biol. Chem. 273, 28,346-28,354). We have now found that the anti-p59S
      antibodies recognize centrosomes and midbodies of dividing cells. alphaB
      Crystallin was the only protein recognized by the anti-p59S antibodies in Western
      blot analyses of isolated centrosome fractions. alphaB-Crystallin phosphorylated
      at Ser-59 was localized at the microtubule organizing centers by means of double
      staining with anti-beta-tubulin antibody in aster formation analysis and was co
      localized with gamma-tubulin in centrosomes. Gamma-Tubulin was co
      immunoprecipitated with alphaB-crystallin in U373 glioma cell extracts. On the
      other hand, the location of the phosphorylated alphaB-crystallin deviated from
      that of alpha-tubulin or gamma-tubulin in the midbody region. Taken together with
      the evidences that several chaperones are distributed to centrosomes, these
      results suggest that alphaB-crystallin as a chaperone might be also involved in
      the quality control of proteins.

PMID- 11831388
TI  - EB 1 immunofluorescence reveals an increase in growing astral microtubule length
      and number during anaphase in NRK-52E cells.
AB  - Spindle positioning in animal cells is thought to rely upon the interaction of
      astral microtubules with the cell cortex. Information on the dynamics of astral
      microtubules during this process is scarce, in part because of the difficulty in
      visualising these microtubules by light microscopy. EB1 is a protein which
      specifically localises to growing microtubule distal tips. Immunostaining for EB1
      therefore represents a powerful method for visualising the distribution of
      growing microtubule tips within cells. In this study we used EB1 immunostaining
      in mitotic NRK-52E cells to quantitatively analyse the length and number of
      growing astral microtubules during metaphase and anaphase. We observed a dramatic
      increase in growing astral microtubule length and number during anaphase.
      Furthermore, drug treatments which specifically destroyed astral microtubules
      resulted in an increase in misaligned anaphase but not metaphase spindles. We
      suggest that an anaphase-specific increase in growing astral microtubule length
      and number facilitates the maintenance of a correctly aligned spindle in mitotic
      NRK-52E cells.

PMID- 11831389
TI  - Membrane sorting in the endocytic and phagocytic pathway of Dictyostelium
      discoideum.
AB  - To study sorting in the endocytic pathway of a phagocytic and macropinocytic
      cell, monoclonal antibodies to membrane proteins of Dictyostelium discoideum were
      generated. Whereas the p25 protein was localized to the cell surface, p80 was
      mostly present in intracellular endocytic compartments as observed by
      immunofluorescence as well as immunoelectron microscopy analysis. The p80 gene
      was identified and encodes a membrane protein presumably involved in copper
      transport. Expression of chimeric proteins revealed that the cytoplasmic domain
      of p80 was sufficient to cause constitutive endocytosis and localization of the
      protein to endocytic compartments. Dileucine- and tyrosine-based endocytic
      signals described previously in mammalian systems were also capable of targeting
      chimera to endocytic compartments. In phagocytosing cells no membrane sorting was
      observed during formation of the phagosome. Both p25 and p80 were incorporated
      non-selectively in nascent phagosomes, and then retrieved shortly after phagosome
      closure. Our results emphasize the fact that very active membrane traffic takes
      place in phagocytic and macropinocytic cells. This is coupled with precise
      membrane sorting to maintain the specific composition of endocytic compartments.

PMID- 11831390
TI  - The apical localization of SGLT1 glucose transporter is determined by the short
      amino acid sequence in its N-terminal domain.
AB  - SGLT1, an isoform of Na+-dependent glucose cotransporters, is localized at the
      apical plasma membrane in the epithelial cells of the small intestine and the
      kidney, where it plays a pivotal role in the absorption and reabsorption of
      sugars, respectively. To search the domain responsible for the apical
      localization of SGLT1, we constructed an N-terminal deletion clone series of rat
      SGLT1 and analyzed the localization of the respective products in Madin-Darby
      canine kidney (MDCK) cells. The products of N-terminal deletion clones up to the
      19th amino acid were localized at the apical plasma membrane, whereas the
      products of N-terminal 20- and 23-amino-acid deletion clones were localized along
      the entire plasma membrane. Since single-amino-acid mutations of either D28N or
      D28G in the N-terminal domain give rise to glucose/galactose malabsorption
      disease, we examined the localization of these mutants. The products of D28N and
      D28G clones were localized in the cytoplasm, showing that the aspartic acid-28
      may be essential for the delivery of SGLT1 to the plasma membrane. These results
      suggest that a short amino acid sequence of the N-terminal domain of SGLT1 plays
      important roles in plasma membrane targeting and specific apical localization of
      the protein.

PMID- 11831391
TI  - A parafusin-related Toxoplasma protein in Ca2+-regulated secretory organelles.
AB  - We cloned a gene, PRPI, of Toxoplasma gondii encoding a 637-amino-acids protein
      having a calculated mass of 70 kDa. The sequence showed high homology to
      parafusin, a protein that in Paramecium tetraurelia participates in Ca2+
      regulated exocytosis and is a paralog of phosphoglucomutase. We show that
      Toxoplasma gondii homogenate and an expressed recombinant PRP1 fusion protein
      cross-react with a specific peptide-derived antibody to parafusin in Western
      blots. Antibodies to the recombinant PRP1 showed cross-reaction with parafusin
      and recognized PRP1, as bands at M, 63 x 10(3) and 68 x 10(3), respectively. PRP1
      is labeled when Toxoplasma gondii cells are incubated with inorganic 32P and
      appears as the major band on autoradiograms of SDS-PAGE gels. The localization of
      PRP1 was examined in secretory organelles of Toxoplasma gondii by deconvolution
      light microscopy followed by three dimensional reconstruction using pairwise
      combinations of specific antibodies. PRP1 localized to the apical third of the
      cell. It co-localized with micronemes, the only secretory organelle the secretion
      of which is Ca2+ dependent. Quantification of the co-localized stain suggests
      that only mature micronemes ready for exocytosis have PRP1. These findings
      suggest that PRP1, parafusin and other members of the phosphoglucomutase
      superfamily have a conserved role in Ca2+-regulated exocytic processes.

PMID- 11831392
TI  - Sialosyl Le(a)-carrying gangliosides present on the surface of colon carcinoma
      cells are not directly involved in adhesion to E-selectin.
AB  - We have shown previously that human colon cancer CX-1 cells contain lipid- and
      protein-bound sialosyl Lewis(a) structures that support the adhesion of these
      cells to E-selectin. Treatment of cancer cells with O-sialoglycoprotease did not
      decrease either the binding of anti-sialosyl Le(a) antibodies or binding to E
      selectin-expressing CHO cells. This suggested that cleavage of sialomucins
      uncovered cryptic sialosyl Le(a) gangliosides that support such interactions. In
      the present study, inhibitors of glycolipid and O-glycan biosynthesis, d,l-threo
      PPPP and GalNAc-alpha-O-benzyl, respectively, were used to study whether the
      binding of anti-sialosyl Le(a) antibody and adhesion of CX-1 cells to E-selectin
      can be mediated by sialosyl Le(a) gangliosides. Treatment of cancer cells with
      each of the inhibitors decreased the expression of the respective glycoconjugates
      as shown by TLC-binding assay and immunoblotting with anti-sialosyl Le(a)
      antibody. However, only slight differences in binding of antisialosyl Le(a)
      antibody to the surfaces of control and inhibitor-treated CX-1 cells were found
      by flow cytometry, as well no differences were observed in binding of control and
      inhibitor-treated CX-1 cells to E-selectin-expressing CHO cells, supporting the
      earlier hypothesis on the involvement of gangliosides in binding of anti-sialosyl
      Lewis(a) in the partial absence of mucin O-glycans. This hypothesis was further
      proven by electron microscopy data. Both native CX-1 and d,l-threo-PPPP-treated
      cells were labelled with anti-sialosyl Lewis(a) antibody mostly at a distance 70
      90 nm from cell surface, suggesting interaction with protein-bound carbohydrate
      structures only. In contrast, the cancer cells treated with GalNAc-alpha-O-benzyl
      showed most of the staining around 20 nm distance from the plasmalemma, implying
      that the antibody interacts with lipid-bound sialosyl Lewis(a) instead. The
      electron microscopy data in conjunction with other results described in this
      report strongly support the hypothesis that sialosyl Lea gangliosides are not
      involved in the adhesion of CX-1 cells to E-selectin when mucins are present on
      the cell surface, but they may be involved in binding to E-selectin in their
      absence.

PMID- 11831394
TI  - From tumor biology to clinical Pet: a review of positron emission tomography
      (PET) in oncology.
AB  - Cancer cells show increased metabolism of both glucose and amino acids, which can
      be monitored with 18F-2-deoxy-2-fluoro-D-glucose (FDG), a glucose analogue, and
      11C-L-methionine (Met), respectively. FDG uptake is higher in fast-growing than
      in slow-growing tumors. FDG uptake is considered to be a good marker of the grade
      of malignancy. Several studies have indicated that the degree of FDG uptake in
      primary lung cancer can be used as a prognostic indicator. Differential diagnosis
      of lung tumors has been studied extensively with both computed tomography (CT)
      and positron emission tomography (PET). It has been established that FDG-PET is
      clinically very useful and that its diagnostic accuracy is higher than that of
      CT. Detection of lymph node or distant metastases in known cancer patients using
      a whole-body imaging technique with FDG-PET has become a good indication for PET.
      FDG uptake may be seen in a variety of tissues due to physiological glucose
      consumption. Also FDG uptake is not specific for cancer. Various types of active
      inflammation showed FDG uptake to a certain high level. Understanding of the
      physiological and benign causes of FDG uptake is important for accurate
      interpretation of FDG-PET. In monitoring radio/chemotherapy, changes in FDG
      uptake correlate with the number of viable cancer cells, whereas Met is a marker
      of proliferation. Reduction of FDG uptake is a sensitive marker of viable tissue,
      preceding necrotic extension and volumetric shrinkage. FDG-PET is useful for the
      detection of recurrence and for monitoring the therapeutic response of tumor
      tissues in various cancers, including those of the lung, colon, and head and
      neck. Thus, PET, particularly with FDG, is effective in monitoring cancer cell
      viability, and is clinically very useful for the diagnosis and detection of
      recurrence of lung and other cancers.

PMID- 11831393
TI  - Comparative distribution of short dystrophin superfamily products in various
      guinea pig spermatozoa domains.
AB  - In this study, the presence and cellular distribution of dystrophin family
      products (i.e. Dp71d, Dp71f-like protein and dystrobrevin) was examined by
      indirect immunofluorescence and Western blotting in guinea pig spermatozoa. Two
      dystrophin-associated proteins, beta-dystroglycan and alpha-syntrophin, and nNOS
      a protein frequently associated with alpha-syntrophin, were determined. In
      spermatozoa lacking plasma membrane and acrosome, Dp71f-like protein was found in
      the postacrosomal perinuclear theca and also in the middle piece of the
      flagellum. In the flagellum, Dp71f-like protein is localized together with alpha
      syntrophin and nNOS. Dp71d was present in the plasma membrane of the middle piece
      with beta-dystroglycan, alpha-syntrophin and nNOS. Dp71d was also present in
      plasma membrane of the post acrosomal region, but only with nNOS. Finally,
      dystrobrevin was located all along skeletal flagellum structures and in the
      subacrosomal hemisphere of the perinuclear theca. This distinct and complementary
      distribution in various domains of spermatozoa may reveal a specific function for
      each short dystrophin family product, in the stabilization of the domains where
      they are located.

PMID- 11831395
TI  - The CdTe detector module and its imaging performance.
AB  - In recent years investigations into the application of semiconductor detector
      technology in gamma cameras have become active world-wide. The reason for this
      burst of activity is the expectation that the semiconductor-based gamma camera
      would outperform the conventional Anger-type gamma camera with a large
      scintillator and photomultipliers. Nevertheless, to date, it cannot be said that
      this expectation has been met. METHODS: While most of the studies have used CZT
      (Cadmium Zinc Telluride) as the semiconductor material, we designed and
      fabricated an experimental detector module of CdTe (Cadmium Telluride). The
      module consists of 512 elements and its pixel pitch is 1.6 mm. We have evaluated
      its energy resolution, planar image performance, single photon emission computed
      tomography (SPECT) image performance and time resolution for coincidence
      detection. RESULTS: The average energy resolution was 5.5% FWHM at 140 keV. The
      intrinsic spatial resolution was 1.6 mm. The quality of the phantom images, both
      planar and SPECT, was visually superior to that of the Anger-type gamma camera.
      The quantitative assessment of SPECT images showed accuracy far better than that
      of the Anger-type camera. The coincidence time resolution was 8.6 ns. All
      measurements were done at room temperature, and the polarization effect that had
      been the biggest concern for CdTe was not significant. CONCLUSION: The results
      indicated that the semiconductor-based gamma camera is superior in performance to
      the Anger-type and has the possibility of being used as a positron emission
      computed tomography (PET) scanner.

PMID- 11831396
TI  - Prevalence of deep venous thrombosis in the lower limbs and the pelvis and
      pulmonary embolism in patients with positive antiphospholipid antibodies.
AB  - BACKGROUND: Antiphospholipid antibodies (AA) are immunoglobulins that cross-react
      with phospholipid on cell membrane, and are therefore associated with a
      hypercoagulable state manifested by arterial/venous thromboses. We aimed to
      determine the prevalence of deep venous thrombosis in the lower limbs and the
      pelvic region (DVT) and pulmonary embolism (PE) in patients with positive AA.
      METHODS: Sixty-six patients (48 female, 18 male) with positive lupus
      anticoagulant (LA) and/or positive anticardiolipin antibody (aCL) underwent
      radionuclide (RN) venography with 370 MBq of 99mTc-MAA. Pulmonary perfusion
      scintigraphy was performed in 58 patients. Fifteen patients had positive LA and
      positive aCL (LA+/aCL+), 33 patients had positive LA only (LA+/ aCL-) and 18
      patients had positive aCL only (LA-/aCL+). 43 patients were diagnosed with
      primary antiphospholipid syndrome (APS) and 19 were diagnosed with APS associated
      with SLE. RESULTS: DVT was detected in 21 of 66 patients (32%). Patients with
      LA+/aCL+ showed higher prevalence of DVT (53%) as compared to LA+/aCL- (27%) and
      LA-/aCL+ (22%). PE was found in 13 of 58 patients (22%). The prevalence of PE was
      higher in patients with positive aCL (33% in LA+/aCL+; 36% in LA-/aCL+) than in
      patients with negative aCL (10%). CONCLUSION: Because of the high prevalence of
      DVT and PE in patients with AA, RN scintigraphy must be recommended in screening
      for these clinical troubles. These results indicate that the prevalence of DVT
      and PE may vary in subgroups of AA.

PMID- 11831397
TI  - Retention mechanism of hypoxia selective nuclear imaging/radiotherapeutic agent
      cu-diacetyl-bis(N4-methylthiosemicarbazone) (Cu-ATSM) in tumor cells.
AB  - The retention mechanism of the novel imaging/radiotherapeutic agent, Cu-diacetyl
      bis(N4-methylthiosemicarbazone) (Cu-ATSM) in tumor cells was clarified in
      comparison with that in normal tissue in vitro. With Cu-ATSM and reversed phase
      HPLC analysis, the reductive metabolism of Cu-ATSM in subcellular fractions
      obtained from Ehrlich ascites tumor cells was examined. As a reference, mouse
      brain was used. To determine the contribution of enzymes in the retention
      mechanisms, and specific inhibitor studies were performed. In subcellular
      fractions of tumor cells, Cu-ATSM was reduced mainly in the microsome/cytosol
      fraction rather than in the mitochondria. This finding was completely different
      from that found in normal brain cells. The reduction process in the
      microsome/cytosol was heat-sensitive and enhanced by adding exogenous NAD(P)H, an
      indication of enzymatic reduction of Cu-ATSM in tumor cells. Among the known
      bioreductive enzymes, NADH-cytochrome b5 reductase and NADPH-cytochrome P450
      reductase in microsome played a major role in the reductive retention of Cu-ATSM
      in tumors. This enzymatic reduction was enhanced by the induction of hypoxia.
      Radiocopper labeled Cu-ATSM provides useful information for the detection of
      hypoxia as well as the microsomal bioreductive enzyme expression in tumor.

PMID- 11831398
TI  - The role of whole-body FDG-PET in preoperative assessment of tumor staging in
      oral cancers.
AB  - OBJECTIVE: The aim of this study is to clarify the clinical utility of 2-deoxy-2
      [18F]fluoro-D-glucose (FDG) positron emission tomography (PET) in determining the
      TNM classification in patients with oral cancer. METHODS: Twenty-five consecutive
      patients (14 male and 11 female; age range, 40 yr to 86 yr) with oral cancer were
      included in this study. The diagnostic accuracy for detecting cervical lymph
      nodes was investigated by comparing the results of CT and/or MRI and physical
      findings. For the semi-quantitative analysis, the tumor standardized uptake value
      (SUV) and tumor to background SUV ratio (T/B ratio) were assessed in primary
      tumors and cervical lymph nodes. RESULTS: All primary lesions were visualized on
      FDG-PET images. Even though artifacts from dental materials near the lesion
      hampered the delineation of primary tumors on CT/MRI, the extent of primary
      tumors was accurately assessed by FDG-PET. The SUV and T/B ratio in the primary
      tumor classified in higher T grade (T3 and T4) was significantly higher than that
      in lower T grade (T1 and T2) (mean +/- SD of SUV; 8.32 +/- 2.99 vs. 5.15 +/-
      3.77, p < 0.01, mean +/- SD of T/B ratio; 6.96 +/- 3.23 vs. 3.61 +/- 2.76, p <
      0.01). The SUV and T/B ratio of metastatic lymph nodes were also significantly
      higher than those of normal lymph nodes (mean +/- SD of SUV; 3.39 +/- 1.69 vs.
      1.55 +/- 0.57, p < 0.001, mean +/- SD of T/B ratio; 2.46 +/- 1.08 vs. 1.03 +/-
      0.22, p < 0.001). Among these three methods, FDG-PET in conjunction with CT/MRI
      showed the highest accuracy of 92%, but there were no significant differences in
      diagnostic accuracy among the three methods. For the semi-quantitative analysis,
      a threshold SUV of 2.0 provided 100% sensitivity, 82% specificity, and 88%
      accuracy. Furthermore, a threshold T/B ratio of 1.5 provided 100% sensitivity,
      100% specificity, and 100% accuracy. Regarding the detection of distant
      metastasis, there was one positive result in FDG-PET showing distant pulmonary
      metastasis. CONCLUSIONS: Whole-body FDG-PET is an effective and convenient
      diagnostic tool for the evaluation of tumor staging in patients with oral cancer.
      Tumor staging by whole-body FDG-PET may, in fact, supplement the conventional
      staging by means of CT/MRI and physical findings.

PMID- 11831399
TI  - Evaluation of crossed cerebellar diaschisis in 30 patients with major cerebral
      artery occlusion by means of quantitative I-123 IMP SPECT.
AB  - Quantitative crossed cerebellar diaschisis (CCD) and the correlation with a
      reduction in supratentorial regional cerebral blood flow (rCBF) and
      cerebrovascular reserve capacity (CVR) were investigated in clinically stable
      patients with major cerebral artery occlusion by the iodine-123-N-isopropyl-p
      iodoamphetamine (I-123 IMP) single photon emission computed tomography (SPECT)
      method. Thirty patients with major cerebral artery occlusion underwent SPECT by
      the I-123 IMP autoradiographic method. Regional CBF was measured in the cerebral
      hemisphere, frontal and parietal lobes, temporo-parietal lobe, and cerebellum
      both at rest and after administration of acetazolamide. Eighteen of 30 patients
      (60%) had CCD. CCD was significantly related to magnetic resonance imaging
      evidence of infarction. Quantitative CCD was 17% and the CVR in the cerebellum
      was preserved in patients with CCD. There was a significant difference in CBF and
      CVR between the affected and normal sides in all regions of interest in the
      patients without CCD [CBF (ml/100 g/min): hemisphere (H), normal side (N): 31.4
      +/- 6.8, affected side (A): 27.5 +/- 7.4; p < 0.05. CVR: H, N: 0.56 +/- 0.38, A:
      0.42 +/- 0.18; p < 0.01]. CCD is common in patients with major cerebral artery
      occlusion, and quantitative I-123 IMP SPECT is helpful in detecting CCD in
      clinically stable patients with occlusion of major cerebral arteries.

PMID- 11831400
TI  - Receiver operating characteristic (ROC) analysis of images reconstructed with
      iterative expectation maximization algorithms.
AB  - PURPOSE: The quality of images reconstructed by means of the maximum likelihood
      expectation maximization (ML-EM) and ordered subset (OS)-EM algorithms, was
      examined with parameters such as the number of iterations and subsets, then
      compared with the quality of images reconstructed by the filtered back projection
      method. METHODS: Phantoms showing signals inside signals, which mimicked single
      photon emission computed tomography (SPECT) images of cerebral blood flow and
      myocardial perfusion, and phantoms showing signals around the signals obtained by
      SPECT of bone and tumor were used for experiments. To determine signals for
      recognition, SPECT images in which the signals could be appropriately recognized
      with a combination of fewer iterations and subsets of different sizes and
      densities were evaluated by receiver operating characteristic (ROC) analysis. The
      results of ROC analysis were applied to myocardial phantom experiments and
      scintigraphy of myocardial perfusion. RESULTS: Taking the image processing time
      into consideration, good SPECT images were obtained by OS-EM at iteration No. 10
      and subset 5. CONCLULSION: This study will be helpful for selection of parameters
      such as the number of iterations and subsets when using the ML-EM or OS-EM
      algorithms.

PMID- 11831401
TI  - Usefulness of indium-111-oxine-labeled leukocyte scintigraphy in diagnosis of
      inflammation associated with chronic aortic dissection.
AB  - BACKGROUND: Patients with chronic aortic dissection require monitoring for
      indications of disease progression. In present study, inflammation adjacent to
      associated aortic wall was evaluated by indium-111-oxine-labeled leukocyte
      scintigraphy, scince inflammation of the blood vessel wall often associates with
      progression of chronic aortic dissection. METHODS AND RESULTS: Fifteen patients
      with aortic dissection underwent indium-111-oxine-labeled leukocyte scintigraphy.
      Seven showed positive images at sites corresponding to the actual sites of the
      dissociated aorta. Four patients with positive images underwent surgery.
      Histologic examination revealed inflammatory and necrotic changes of the aortic
      wall. During a mean follow-up period of 2.3 years, progression of aortic
      dissection was observed in two of the seven patients with positive intimal
      imaging. CONCLUSION: Indium-111-oxine-labeled leukocyte scintigraphy may be a
      useful noninvasive technique to assess the persistent inflammation in patients
      with chronic aortic dissection.

PMID- 11831402
TI  - Use of digirad 2020tc Imager, a multi-crystal scintillation camera with solid
      state detectors in one case for the imaging of autografts of parathyroid glands.
AB  - 99mTc-methoxy-isobutyl-isonitrile (99mTc-MIBI) scintigraphy with Digirad 2020tc
      ImagerTM (2020tc), which was a multi-crystal scintillation camera with solid
      state detectors was performed for patients with secondary hyperparathyroidism
      having autografts of parathyroid glands in the right arm. With the 2020tc camera,
      three abnormal accumulations were found in the right arm. The images obtained
      with this camera were superior in resolution to those obtained with a
      conventional NaI crystal gamma camera (ZLC7500, Siemens, Germany). The next day,
      resection of autografts of parathyroid glands was done. Four hyperplastic
      parathyroid glands were resected and all were hyperplastic in pathological
      findings.

PMID- 11831403
TI  - Positivity of extrapulmonary Ga-67 uptake in sarcoidosis: thyroid uptake due to
      chronic thyroiditis and bone uptake due to fibrous dysplasia.
AB  - Ga-67 citrate scintigraphy was performed on a 29-year-old man who had been
      diagnosed as having pulmonary sarcoidosis by a transbronchial lung biopsy. A Ga
      67 citrate scintigram showed increased uptake not only in the pulmonary hilum and
      mediastinum, but also in the thyroid gland and the right ilium. Chronic
      thyroiditis was confirmed by aspiration biopsy of the thyroid gland, and fibrous
      dysplasia was confirmed by CT guided biopsy of the right ilium. Extrapulmonary Ga
      67 uptake in patients with sarcoidosis does not necessarily indicate the
      involvement of other tissues and organs.

PMID- 11831404
TI  - Re: Quiz.

PMID- 11831405
TI  - Multiple bone metastases of hepatocellular carcinoma.

PMID- 11831406
TI  - Thinking and caring about cognitive inconsistency: when and for whom does
      attitudinal ambivalence feel uncomfortable?
AB  - The relation between conflicting evaluations of attitude objects (potential
      ambivalence) and associated unpleasant feelings (felt ambivalence) was
      investigated. Participants indicated their potential and felt ambivalence about
      capital punishment (Studies 1 and 2) and abortion (Studies 1-3). The simultaneous
      accessibility (J. N. Bassili, 1996) of participants' potential ambivalence (i.e.,
      how quickly and equally quickly conflicting evaluations came to mind) was
      measured using response latency (Studies 1-3) and manipulated by repeated
      expression (Study 3). The relation between potential ambivalence and felt
      ambivalence was strongest when potential ambivalence was high in simultaneous
      accessibility (Studies 1-3). This pattern was most pronounced for participants
      who were high in preference for consistency (Study 3; R. B. Cialdini, M. R.
      Trost, & T. J. Newsom, 1995). Similarities of ambivalence and cognitive
      dissonance constructs are discussed.

PMID- 11831407
TI  - Looking back in time: self-concept change affects visual perspective in
      autobiographical memory.
AB  - People who change often report that their old selves seem like "different
      people." Correlational (Study 1) and experimental (Studies 2 and 3) studies
      showed that participants tended to use a 3rd-person observer perspective when
      visualizing memories of actions that conflicted with their current self-concept.
      A similar pattern emerged when participants imagined performing actions that
      varied in self-concept compatibility (Study 4). The authors conclude that on-line
      judgments of an action's self-concept compatibility affect the perspective used
      for image construction. Study 5 shows applied implications. Use of the 3rd-person
      perspective when recalling past episodes of overindulgent eating was related to
      optimism about behaving differently at an upcoming Thanksgiving dinner. The
      authors discuss the effect of self-concept compatibility on cognitive and
      emotional reactions to past actions and consider the role of causal attributions
      in defining the self across time.

PMID- 11831408
TI  - Unskilled, unaware, or both? The better-than-average heuristic and statistical
      regression predict errors in estimates of own performance.
AB  - People who score low on a performance test overestimate their own performance
      relative to others, whereas high scorers slightly underestimate their own
      performance. J. Kruger and D. Dunning (1999) attributed these asymmetric errors
      to differences in metacognitive skill. A replication study showed no evidence for
      mediation effects for any of several candidate variables. Asymmetric errors were
      expected because of statistical regression and the general better-than-average
      (BTA) heuristic. Consistent with this parsimonious model, errors were no longer
      asymmetric when either regression or the BTA effect was statistically removed. In
      fact, high rather than low performers were more error prone in that they were
      more likely to neglect their own estimates of the performance of others when
      predicting how they themselves performed relative to the group.

PMID- 11831409
TI  - Unskilled and unaware--but why? A reply to Krueger and Mueller (2002).
AB  - J. Kruger and D. Dunning (1999) argued that the unskilled suffer a dual burden:
      Not only do they perform poorly, but their incompetence robs them of the
      metacognitive ability to realize it. J. Krueger and R. A. Mueller (2002)
      replicated these basic findings but interpreted them differently. They concluded
      that a combination of the better-than-average (BTA) effect and a regression
      artifact better explains why the unskilled are unaware. The authors of the
      present article respectfully disagree with this proposal and suggest that any
      interpretation of J. Krueger and R. A. Mueller's results is hampered because
      those authors used unreliable tests and inappropriate measures of relevant
      mediating variables. Additionally, a regression-BTA account cannot explain the
      experimental data reported in J. Kruger and D. Dunning or a reanalysis following
      the procedure suggested by J. Krueger and R. A. Mueller.

PMID- 11831410
TI  - Exhaustive and heuristic retrieval processes in person cognition: further tests
      of the TRAP model.
AB  - The twofold retrieval by associative pathways (TRAP) model (L. Garcia-Marques &
      D. L. Hamilton, 1996) proposes that two distinct modes of retrieval typically
      underlie recall and frequency estimation. The model accounts for the simultaneous
      occurrence of greater recall of incongruent information and higher frequency
      estimation of congruent information. Three experiments provided further tests of
      the TRAP model. Experiment 1 manipulated cognitive load (at encoding and at
      retrieval) and the selectivity of the retrieval goal. Under either high load or a
      selective retrieval goal, incongruent items ceased to be better recalled.
      Experiment 2 manipulated the accessibility of expectancy-congruent, -incongruent,
      or -neutral episodes and found corresponding effects in frequency estimates.
      Finally, Experiment 3 showed that providing part-list retrieval cues inhibits
      recall but increases frequency estimates. The TRAP model predicted these results.

PMID- 11831411
TI  - Approach versus avoidance: different types of commitment in intimate
      relationships.
AB  - The major objective of the present study was to examine whether approach versus
      avoidance commitment to one's intimate relationship was differentially predictive
      of relationship quality parameters in the long run. In the 1st testing period,
      134 participants (67 romantic couples) answered questions about approach- versus
      avoidance-related measures. Commitment and relationship quality parameters such
      as satisfaction and emotions depending on the partner's presence were assessed in
      all 3 testing periods. The proposed distinction between an approach and an
      avoidance type of commitment was validated through correlations with other
      approach- versus avoidance-related measures. Longitudinal analyses revealed that
      approach commitment predicted relationship quality parameters positively, whereas
      avoidance commitment predicted them negatively. The results are discussed in
      terms of the benefit of an approach-avoidance-based conceptualization of
      commitment.

PMID- 11831412
TI  - "But we've been getting better lately": comparing prospective and retrospective
      views of relationship development.
AB  - What kinds of stories do people wish to tell about the development of their close
      relationships? To address this question, 2 studies of newlyweds compared
      retrospective reports of marital satisfaction over 4 years with prospective data
      on marital satisfaction over the same period. In both studies, growth curve
      analyses revealed that spouses tended to recall satisfaction that had declined in
      the distant past but made up for those declines with recent improvements.
      Prospective reports, however, tended to decline linearly over time. Furthermore,
      Study 2 revealed that current confidence in the future of the relationship was
      associated with perceptions of change in satisfaction but not perceptions of past
      levels of satisfaction. Results suggest that the ability to perceive
      improvements, especially over the recent past, may be a source of hope for
      partners in less satisfying relationships.

PMID- 11831413
TI  - When you and I are "we," you are not threatening: the role of self-expansion in
      social comparison.
AB  - Many theories of self-evaluation emphasize the power of social comparison. Simply
      put, an individual is thought to gain esteem whenever she or he outperforms
      others and to lose esteem when he or she is outperformed. The current research
      explored interdependent self-construal as a moderator of these effects. Two
      studies used a priming task to manipulate the level of self-construal and
      investigate effects of social comparison in dyadic (Study 1) and group situations
      (Study 2). Both studies demonstrated that when the target for comparison is
      construed as part of the self, his or her successes become cause for celebration
      rather than costs to esteem. Additionally, gender differences in chronic
      relational and collective self-construals moderated the patterns of social
      comparison in a form similar to that of priming relational and collective self
      construals.

PMID- 11831414
TI  - Self-esteem, construal, and comparisons with the self, friends, and peers.
AB  - Extending the better than average effect, 3 studies examined self-, friend, and
      peer comparisons of personal attributes. Participants rated themselves as better
      off than friends, who they rated as superior to generalized peers. The exception
      was in direct comparisons, where the self and friends were not strongly
      differentiated on unambiguous negative attributes. Self-esteem and construal
      played moderating roles, with persons with high self-esteem (HSEs) exploiting
      both ambiguous positive and ambiguous negative traits to favor themselves.
      Persons lower in self-esteem exploited ambiguous positive traits in their favor
      but did not exploit ambiguous negative traits. Across self-esteem level, ratings
      of friends versus peers were exaggerated when attributes were ambiguous. HSEs
      seemed to take advantage of ambiguity more consistently to present favorable self
      views; people with low self-esteem used ambiguity to favor their friends but were
      reluctant to minimize their own faults.

PMID- 11831415
TI  - Alzheimer's disease and other dementias: a review.
AB  - Dementia and its associated diseases are important causes of disability and
      morbidity in developed countries, especially in the aged population. As the
      babyboomers arrive at retirement and individuals over 100 are one of the fastest
      growing segments of our nation's population, we may realize the substantial cost
      these diseases bring to society. Dementia is characterized by a significant loss
      of cognitive function and should be clinically distinguished from an acute
      delirium or decreased arousal. Its manifestations cause anguish to millions of
      caregivers and family members, who are pressed to cope with their loved one's
      unfortunate decline in multiple cognitive domains, functioning, and behavior.
      Early detection and management may prevent overuse of costly medical resources
      and allow patients and family members time to prepare for future medical,
      financial, and emotional challenges. Diagnostic clues to the etiology of the
      patient's dementia can be found in a medical workup in which the neurologic
      history and examination (including mental status examination) are essential and
      neuroimaging is indicated. Herein, the concept of central nervous system (CNS)
      degenerative diseases as disorders of specific proteins is introduced. This
      review is intended to summarize clinical, biological, and genetic features of the
      common subtypes of dementia, and bring light to potential benefits of early and
      accurate diagnoses to optimize treatment. Details of the various diseases remain
      only partially uncovered, raising extensive prospects for future research and
      therapy for patients with dementia.

PMID- 11831416
TI  - Slowly progressive aphasia with striatal involvement.
AB  - We have described four patients with slowly progressive aphasia with striatal
      involvement occurring at different stages in the course of the illness. There
      were two males and two females, and their ages ranged from 68 to 76 (mean: 72)
      years. The extrapyramidal signs included tremors, bradykinesia, rigidity, and
      focal dystonia, and one had weakness resembling stroke. There is a heterogeniety
      among patients with slowly progressive aphasia and the clinical features
      correspond to the functional anatomy of the areas involved rather than to the
      pathology.

PMID- 11831417
TI  - Cognitive impairments in multiple sclerosis: a review.
AB  - Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central
      nervous system (CNS). Cognitive impairment (CI) may develop at any time during
      the course of the disease in the presence or absence of neurological disability.
      On the basis of comprehensive neuropsychological studies, there is now a
      consensus among investigators that 45 percent to 65 percent of MS patients suffer
      from some degree and form of cognitive difficulty. Features of CI include
      bradyphrenia; impaired attention, concentration and abstract reasoning; reduced
      manual speed and dexterity; deficits in memory retrieval; and language deficits
      in both the relapsing-remitting and progressive forms of MS. Impairments in all
      cognitive domains may result from the diffuse spread of microscopic pathology,
      although a preferential lobar distribution of plaques can present with a
      predominant deficit in the corresponding cognitive function. Nevertheless, the
      severity of CI best correlates with total microscopic and macroscopic disease
      burden of the brain as defined by recently developed magnetic resonance imaging
      (MRI) sequences. A disruption of connecting intercortical and subcortical
      pathways is likely to be the main cause of metabolic and functional abnormalities
      in neurons. However a direct toxic effect of soluble inflammatory products may
      also compromise neuronal function and survival. Early treatment of MS with
      interferons and copaxone can prevent or delay the onset of both neurological and
      cognitive disabilities by reducing the inflammatory activity and damage in the
      CNS. Until more powerful neuroprotective agents become available, simple
      neuropsychological screening and cognitive rehabilitation for memory and language
      impairments will remain important components in the care of MS patients.

PMID- 11831418
TI  - Primary progressive aphasia: a review of the neurobiology of a common
      presentation of Pick complex.
AB  - Primary progressive aphasia (PPA) is an identifiable and distinct form of
      clinical presentation of focal degenerative disease. The underlying pathology is
      often considered heterogeneous, but we propose that, in fact, this syndrome has a
      characteristic underlying neurobiology related to Pick's disease and
      frontotemporal dementia. The authors reviewed the literature of PPA andfound 58
      cases with autopsy. The majority of the cases had related underlying pathology,
      termed "Pick complex," a form of non-Alzheimer's dementia. This includes Pick's
      disease, corticobasal degeneration, dementia lacking distinctive histology, and
      motor neuron disease inclusions. Several of the cases described with focal
      Alzheimer's pathology do not fulfill the criteria of PPA, but have Alzheimer's
      disease with a major aphasic component.

PMID- 11831419
TI  - Restoring dressing independence in persons with Alzheimer's disease: a pilot
      study.
AB  - PURPOSE: Well meaning nursing facility staff may compromise the independence of
      older adults with dementia by performing activities of daily living for
      residents. We assessed the impact of teaching certified nursing assistants (CNAs)
      to use a graduated prompting procedure to increase dressing independence of
      persons with dementia. DESIGN AND METHODS: This study was conducted in a seven
      bed dementia care unit. Three residents and two CNAs participated in the study.
      We used a repeated-measures experimental design to evaluate the effect of a
      training workshop for CNAs on a strategy for increasing resident engagement in
      self-care activities. RESULTS: During a series of baseline observations, we found
      that CNAs typically dressed residents with minimal resident involvement. Results
      showed that, following the training workshop for CNAs, resident independence in
      dressing increased and range of motion improved. IMPLICATIONS: CNAs can provide
      restorative care that increases dressing independence and range of motion of
      older adults with dementia.

PMID- 11831420
TI  - Dementia consults: predictors of compliance by primary care physicians.
AB  - This study was designed to determine rates of primary care physician compliance
      with recommendations made by physician-consultants at an Alzheimer's disease
      center. A mail survey was sent to primary care physicians, who were asked to
      indicate which recommendations had been implemented and to select reasons for
      lack of adherence. The response rate was 53 percent (49/92). Some 83 percent of
      recommendations were implemented. Compliance with medical recommendations was
      higher (87 percent) than with social or behavioral issues (69 percent). Reasons
      for noncompliance indicated that patient or family barriers were responsible in
      48 percent of cases, while physicians were responsible in 24 percent. These
      findings validate the development of two educational programs: curricula that
      support the primary care physician in conveying the value of these interventions
      and guidelines to assist specialists in communicating treatment recommendations.

PMID- 11831421
TI  - Facilitating access to knowledge and debate in nursing and health care.

PMID- 11831422
TI  - Communication: principal barrier to nurse-consumer partnerships.
AB  - An 8-month pilot study conducted in urban, rural and remote areas of Australia
      sought to identify barriers to nurse-consumer partnerships, as well as strategies
      to overcome these barriers. One hundred and ninety-nine Registered Nurses (RNs)
      and 36 consumers participated across 14 workshops to collect data for the pilot
      study. Analysis of these data found that nurses' perceptions of partnership with
      consumers were diverse. Nevertheless, participants in the workshops identified
      'communication' as the principal barrier to nurse-consumer partnerships. Contexts
      in which communication barriers occur grouped easily under the themes of
      information transfer, documentation, education, personal and interpersonal
      situations, guidelines and policy, organizational structures, politics, resources
      and time. Workshop participants also worked together to identify/recommend
      strategies through which the most important barriers to communication in nurse
      consumer partnerships could be addressed.

PMID- 11831423
TI  - Systematic review of nursing management of urinary tract infections in the
      cognitively impaired elderly client in residential care: is there a hole in
      holistic care?
AB  - A systematic review of the current literature available exposed the deficit in
      nursing research as a resource for planning strategies and procedures in the care
      of a urinary tract infection. The cognitively impaired older client living in
      residential care is at particular risk because of their inability to articulate
      their problems, the subtle presentation of symptoms and the overuse of antibiotic
      therapy that has led to an increase in resistant organisms. The fiscal
      responsibility now required by health authorities highlights the need for a more
      enlightened approach to this distressing condition from those registered nurses
      in the front line of care.

PMID- 11831424
TI  - Developing benchmark inventories to assess the content of telephone consultations
      in accident and emergency departments: use of the Delphi technique.
AB  - The provision of telephone advice to members of the general public from staff
      based in accident and emergency departments is common practice. However, it is
      largely conducted on an ad hoc basis without the use of formal guidelines or
      decision support. The evidence base from which to derive guidelines for the
      telephone assessment and advice of many common conditions is lacking. This study,
      using the Delphi technique, was undertaken to develop a number of benchmarks for
      use as objective measures against which the comprehensiveness of telephone
      assessments could be tested. Consensus views on the essential and desirable items
      to be considered for each of 10 presenting complaints was achieved. It is argued
      that establishing consensus views on clinical topics provides an effective means
      of developing an evidence base where other sources of evidence are lacking.

PMID- 11831425
TI  - Children's postoperative pain at home: family interview study.
AB  - The purpose of this study was to: (i) describe the methods that are used in the
      identification and management of postoperative pain in children aged 1-7 years
      after minor outpatient surgery at home; (ii) to identify parents' perceptions
      regarding children's pain and pain medication; and (iii) to examine parents'
      perceptions of discharge advice. Family interviews with inductive content
      analysis were used to gather information from families of 17 Finnish children
      undergoing minor outpatient surgery at a university hospital in Finland.
      Versatile methods were employed by the parents in the identification and
      management of children's postoperative pain subsequent to discharge from the
      hospital. The children expressed that they had experienced pain relief through
      the administration of pain medication, eating ice-cream and playing. The results
      indicate a need for further research in order to identify what elements of
      parents' perceptions of children's pain and pain medication should receive
      additional attention. In addition, the content, methods of providing and timing
      of discharge advice need to be developed in order to help parents with their
      efforts to achieve maximum pain relief in children after surgery.

PMID- 11831426
TI  - Safety and comfort work of nurses glimpsed through patient narratives.
AB  - The everyday work done by nurses in hospital has a taken-for-granted character,
      yet it has great significance for patient safety, comfort and satisfaction with
      care. Perceptions of how adequately this work is done have a bearing on the
      public image of, and the community's confidence in, the professional nurse. A
      qualitative exploration of patients' perceptions and experiences of comfort and
      discomfort provided glimpses of the safety and comfort work of nurses. This work
      was conceptualized as 'anticipating, managing and limiting threat and
      vulnerability.' Safety work, which is clearly intended to protect and to comfort,
      was generally recognizable to informants, but was at other times unobtrusive and
      puzzling. In addition, nurses' work could take on a routine character, which was
      disconcerting and uncomfortable for informants. Nursing interventions described
      by informants as comforting were predominantly physical, psychological, emotional
      and social. Informants felt safe and comforted when their nurses knew what they
      were doing and seemed to care.

PMID- 11831427
TI  - Effect of polarized light in the healing process of pressure ulcers.
AB  - A trial was conducted to examine the effect of polarized light on pressure ulcers
      of 1st, 2nd and 3rd grades. Patients with two pressure ulcers, one of which
      received the polarized light therapy (experimental ulcer) and the other acting as
      control, were included in the study. The experimental ulcers received treatments
      for 2 weeks consisting a 5 min therapy session each day, excluding weekends, for
      10 days. Experimental and control ulcers were assessed as they appeared on
      admission and reassessed at the end of each week. Fifty-five patients aged 37-85
      years (67.1 +/- 11.9 years) were studied. Pressure ulcers of 1st, 2nd and 3rd
      grades receiving extra treatment with polarized light had increased values of
      epithelial tissue between the first and second assessments of 0-30.9% and between
      the second and third assessments of 30.9-21.7%. Values of the control pressure
      ulcers were, respectively, from 0 to 5.5% and from 5.5% to 3.1%. The mean
      pink/white colour values of the experimental ulcers, between the first and second
      measurements increased significantly compared with the control ulcers (P = 0.021)
      and also increased significantly between the second and third measurements (P =
      0.003). The mean values of 'no and minimal exudate' of the experimental ulcers
      increased significantly between first and second measurements compared with the
      control ulcers (P = 0.001), and similarly, significantly between the second and
      third measurements (P = 0.002). Mean surface areas of the experimental ulcers
      decreased significantly between the first and second measurements from 2.84 to
      2.54 cm2 (P < or = 0.001) and between the first and third measurements from 2.84
      to 2.26 cm2 (P < or = 0.001). Mean surface areas of the control ulcers decreased
      between the first and second measurements from 2.10 to 2.08 cm2 (P < or = 0.42)
      and between the first and third measurements from 2.10 to 2.04 cm2 (P < or =
      0.007). Pressure ulcers subjected to extra treatment with polarized light in the
      early stages (first to third measurements) showed improvement in the healing
      process than the control ulcers.

PMID- 11831428
TI  - Hyperuricaemia and its related factors in Taiwanese middle-aged adults.
AB  - This study used data collected in Chung-Hsing Village to evaluate the
      relationship between hyperuricaemia and cardiovascular risk factors inTaiwanese
      middle-aged adults in May 1998. All of the government employees working at
      theTaiwan Provincial Government in Chung-Hsing Village aged 40-64 years were
      candidates for this study. Only 708 volunteers underwent blood tests. To study
      the significant related factors of hyperuricaemia, the t-test, chi2 analysis and
      multivariate logistic regression were used. The results showed that the
      significant related factors of hyperuricaemia are sex, obesity,
      hypertriglyceridaemia and renal function impairment. Hyperuricaemia is more
      common in middle-aged men than in middle-aged women. It is important to determine
      serum uric acid values if obesity, hypertriglyceridaemia or renal function
      impairment are apparent.

PMID- 11831429
TI  - Amy's Chat Room: health promotion programmes for community dwelling elderly
      adults.
AB  - Clinical nurse specialists in community health nursing promote wellness and
      quality of life in elderly adults who live within the community. Major health
      concerns including inappropriate knowledge of chronic diseases, improper eating
      habits and inadequate nutrition, lack of exercise, and poor social relationships
      among elderly adults residing in a government-supported apartment complex in
      north-eastern Ohio were identified using Neuman's Systems Model. 'Amy's Chat
      Room', a series of health education programmes on disease prevention, including
      appropriate nutrition and exercise, was developed and implemented based on the
      PRECEDE-PROCEED programme-planning model. Evaluation of the programmes indicated
      positive results for the older adults that increased their knowledge and
      awareness of disease prevention and modifications in lifestyle, and were
      encouraged to promote supportive relationships. Implications for clinical nurse
      specialist roles within community health nursing were discussed.

PMID- 11831430
TI  - Nurses' perceptions of care and caring.
AB  - Care and caring have been identified as inherently difficult concepts to define,
      but many authors believe that care is the central and unifying core of nursing.
      It is vital that nurses understand what care is, with the current issues about
      measuring and justifying exactly what they do for patients in order to be clear
      about what good care is. If nurses are to constantly improve the care they give,
      they need to be clearer about how to care for patients. Nurses need to make sure
      that they are giving the patients what they want and not what the nurses want.
      This review of the literature explores nurses' perceptions of care and compares
      it with what patients want in terms of care. It also highlights some important
      and interesting differences between what patients and nurses perceive as good
      care.

PMID- 11831431
TI  - Rapid assessment of injuries among survivors of the terrorist attack on the World
      Trade Center--New York City, September 2001.
AB  - On September 11, 2001, a jet aircraft crashed into the north tower of the World
      Trade Center (WTC) in lower Manhattan. Minutes later, a second aircraft crashed
      into the south tower. The impact, fires, and subsequent collapse of the buildings
      resulted in the deaths of thousands of persons. The precise number and causes of
      deaths could not be assessed in the immediate aftermath of the attack; however,
      data were available on the frequency and type of injuries among survivors (Figure
      1). In previous disasters, such information assisted in characterizing type and
      severity of injuries and the health-care services needed by survivors. To assess
      injuries and use of health-care services by survivors, the New York City
      Department of Health (NYCDOH) conducted a field investigation to review emergency
      department (ED) and inpatient medical records at the four hospitals closest to
      the crash site and a fifth hospital that served as a burn referral center. This
      report summarizes findings of that assessment, which indicated that the arrival
      of injured persons to this sample of hospitals began within minutes of the attack
      and peaked 2 to 3 hours later. Among 790 injured survivors treated within 48
      hours, approximately 50% received care within 7 hours of the attack, most for
      inhalation or ocular injuries; 18% were hospitalized. Comprehensive surveillance
      of disaster-related health effects is an integral part of effective disaster
      planning and response.

PMID- 11831432
TI  - Nutritional assessment of children after severe winter weather--Mongolia, June
      2001.
AB  - During 1999-2001, Mongolia (2000 population: 2.7 million) experienced consecutive
      dzuds (i.e., a severe winter with extreme cold and heavy snowfall that causes
      mass debilitation and death of livestock and jeopardizes the lives of herders who
      depend on their animals for food, fuel, income, and transportation) that resulted
      in a loss of nearly six million of the country's 33 million livestock. As a
      result, severe psychological stress and increased school drop-out rates have been
      reported, and increased migration of rural herders into urban centers has placed
      a burden on water, sanitation, medical, and social services. This disaster
      threatened the health and food security of approximately 40% of the country's
      population. The Mongolian Ministry of Health asked the World Health Organization
      (WHO) and the United Nations Children's Fund (UNICEF) for assistance in assessing
      the nutritional effects of the 2000-2001 dzud on children aged 6-59 months. This
      report summarizes the results of that assessment, which indicated that affected
      districts had no excess nutritional wasting in any age group; however, excess
      growth stunting and anemia were common in both affected and unaffected districts.
      Expanded monitoring of this population is needed to determine the causes of
      malnutrition and to develop appropriate interventions.

PMID- 11831433
TI  - Outbreak of Salmonella serotype Kottbus infections associated with eating alfalfa
      sprouts--Arizona, California, Colorado, and New Mexico, February-April 2001.
AB  - On March 12, 2001, the California Department of Health Services (CDHS) identified
      a cluster of Salmonella Kottbus isolates with indistinguishable pulsed-field gel
      electrophoresis (PFGE) patterns. During February 1-May 1, CDHS identified 23
      patients with S. Kottbus infections in several California counties and an
      additional patient from Arizona. This report summarizes the results of the
      investigation of this outbreak, which identified cases in four states and
      implicated alfalfa sprouts produced at a single facility.

PMID- 11831434
TI  - Pathogenesis of African swine fever virus in Ornithodoros ticks.
AB  - African swine fever virus (ASFV) is the only known DNA arbovirus and the sole
      member of the family Asfarviridae. It causes a lethal, hemorrhagic disease in
      domestic pigs. ASFV is enzootic in sub-Saharan Africa and is maintained in a
      sylvatic cycle by infecting both wild members of the Suidae (e.g. warthogs) and
      the argasid tick Ornithodoros porcinus porcinus. The pathogenesis of ASFV in O.
      porcinus porcinus ticks is characterized by a low infectious dose, lifelong
      infection, efficient transmission to both pigs and ticks, and low mortality until
      after the first oviposition. ASFV pathogenesis in warthogs is characterized by an
      inapparent infection with transient, low viremic titers. Thus O. porcinus
      porcinus ticks probably constitute the most important natural vector of ASFV,
      although both the mammalian and tick hosts are probably required for the
      maintenance of ASFV in the sylvatic cycle. The mechanism of ASFV transmission
      from the sylvatic cycle to domestic pigs is probably through infected ticks
      feeding on pigs. In addition to O. porcinus porcinus, a number of North American,
      Central American and Caribbean species of Ornithodoros have been shown to be
      potential vectors of ASFV.

PMID- 11831435
TI  - Identification of virulence attributes of gastrointestinal Escherichia coli
      isolates of veterinary significance.
AB  - The pathogenic strains of Escherichia coli recovered from the intestinal tract of
      animals fall into categories called enterotoxigenic, enteropathogenic,
      enterohemorrhagic and necrotoxigenic. The other two categories, enteroinvasive
      and enteroaggregative, have not been reported in animals. The pathogenicity of
      these strains is determined by the presence of certain genes that encode adhesins
      and toxins, are generally organized in large blocks in chromosomes, large
      plasmids or phages, and are often transmitted horizontally between strains. In
      this review, we summarize current knowledge of the virulence attributes that
      determine the pathogenic potential of E. coli strains and the methods available
      to assess the virulence of the strains. We also discuss the clinical symptoms,
      the gross and histological lesions, and the molecular diagnostic methods our
      laboratories have implemented for detecting pathogenic strains of E. coli that
      are isolated from the gastrointestinal tract of animals.

PMID- 11831436
TI  - Mycobacterium paratuberculosis and the bovine immune system.
AB  - Mycobacterium avium subspecies paratuberculosis (M. paratuberculosis) is the
      causative agent of Johne's disease, a deadly intestinal ailment of ruminants.
      Johne's disease is of tremendous economic importance to the worldwide dairy
      industry, causing major losses due to reduced production and early culling of
      animals. A highly controversial but developing link between exposure to M.
      paratuberculosis and human Crohn's disease in some individuals has led to the
      suggestion that M. paratuberculosis is also a potential food safety concern. As
      with many other mycobacteria, M. paratuberculosis is exquisitely adapted to
      survival in the host, despite aggressive immune reactions to these organisms. One
      hallmark of mycobacteria, including M. paratuberculosis, is their propensity to
      infect macrophages. Inside the macrophage, M. paratuberculosis interferes with
      the maturation of the phagosome by an unknown mechanism, thereby evading the
      host's normal first line of defense against bacterial pathogens. The host immune
      system begins a series of attacks against M. paratuberculosis-infected
      macrophages, including the rapid deployment of activated gammadelta T cells, CD4+
      T cells and cytolytic CD8+ T cells. These cells interact with the persistently
      infected macrophage and with each other through a complex network of cytokines
      and receptors. Despite these aggressive efforts to clear the infection, M.
      paratuberculosis persists and the constant struggle of the immune system leads to
      pronounced damage to the intestinal epithelial cells. Enhancing our ability to
      control this important and tenacious pathogen will require a deeper understanding
      of how M. paratuberculosis interferes with macrophage action, the cell types
      involved in the immune response, the cytokines these cells use to communicate,
      and the host genetic factors that control the response to infection.

PMID- 11831437
TI  - Evolution and function of tandem repeats in the major surface protein 1a of the
      ehrlichial pathogen Anaplasma marginale.
AB  - The major surface protein (MSP) 1a of the ehrlichial cattle pathogen Anaplasma
      marginale, encoded by the single-copy gene msp1alpha, has been shown to have a
      neutralization-sensitive epitope and to be an adhesin for bovine erythrocytes and
      tick cells. msp1alpha has been found to be a stable genetic marker for the
      identification of geographic isolates of A. marginale throughout development in
      acutely and persistently infected cattle and in ticks. The molecular weight of
      MSP1a varies among geographic isolates of A. marginale because of a varying
      number of tandemly repeated peptides of 28-29 amino acids. Variation in the
      sequence of the tandem repeats occurs within and among isolates, and may have
      resulted from evolutionary pressures exerted by ligand-receptor and host-parasite
      interactions. These repeated sequences include markers for tick transmissibility
      that may be important in the identification of ehrlichial pathogens because they
      may influence control strategies and the design of subunit vaccines.

PMID- 11831439
TI  - Effects of cytokine gene therapy on particulate-induced inflammation in the
      murine air pouch.
AB  - Retroviral vectors encoding the human IL-1 antagonist (IL-1Ra) gene and the human
      tumor necrosis factor soluble receptor (sTNF-R) gene were investigated using an
      in vivo model of the inflammatory response to orthopedic wear debris. Air pouches
      established in BALB/c mice were injected with polymethylmethacrylate (PMMA)
      particles to provoke an inflammatory reaction, and infected with retroviral
      vectors expressing IL-1Ra, sTNF-R or a LacZ marker gene. Pouch membranes and
      fluids were harvested after 48 or 72 hours for analyses. Positive PCR reactions
      for Neo genes were observed specifically in DNA extracted from the membrane of
      retroviral-infected pouches. ELISA assays revealed the presence of human IL-1 Ra
      in pouch fluid from DFG-IRAP-Neo transduced mice, but not control animals.
      Histological evaluation indicated that the IL-1Ra gene transfer was associated
      with markedly decreased inflammation in the model, with resolution of the
      edematous phase of the reaction, decreased pouch fluid accumulation, and lowered
      macrophage influx. The data suggest that the air pouch model represents a useful
      tool to evaluate gene therapy, and demonstrate that IL-1Ra gene therapy may be an
      appropriate therapeutic approach to inflammation.

PMID- 11831438
TI  - Effects of all-trans-retinoic acid (atRA) on inducible nitric oxide synthase
      (iNOS) activity and transforming growth factor beta-1 production in experimental
      anti-GBM antibody-mediated glomerulonephritis.
AB  - Sustained high output release of Nitric oxide (NO) as result of activation of
      inducible nitric oxide synthase (iNOS), and increased production of the
      antiproliferative/profibrotic cytokine transforming growth factor-beta1 (TGF
      beta1) are well documented in glomerulonephritis. Modulation of iNOS activity and
      of TGF-beta1 production can therefore be viewed as anti-inflammatory strategies.
      The present study employed all-trans retinoic acid (atRA) which is known to have
      anti-inflammatory effects and to modulate expression of iNOS and TGF-beta1, in
      order to explore its effect on iNOS enzyme activity and TGF-beta1 production in
      anti-GBM antibody induced glomerulonephritis. Glomerulonephritis was induced in
      Lewis rats by injection of anti-GBM antibody. A group of nephritic rats were
      given daily administration of atRA for 14-16 days. Extent of proteinuria was
      assessed by measuring urine protein and creatinine excretion. iNOS enzyme
      activity was measured by calculating conversion of L[14C]arginine to L
      [14C]citrulline in glomerular protein lysates. Levels of TGF-beta1 in glomerular
      protein lysates were measured by quantitative ELISA. Levels of proliferating
      nuclear antigen (PCNA), TGF-beta receptor II (TGFbeta-RII), and fibronectin were
      assessed by Western blot analysis. Glomerular iNOS activity in atRA treated
      nephritic animals was attenuated in comparison to that in nephritic controls that
      were not. Glomerular expression of PCNA was also reduced. Levels of TGF-beta1
      were increased in glomeruli of atRA treated nephritic animals. In these animals,
      there was no change in glomerular levels of TGF-beta receptor II (TGFbeta-RII) or
      fibronectin. and there was no reduction in urine protein excretion. These results
      suggest that atRA attenuates iNOS activity and proliferation in glomeruli of
      nephritic animals. The failure of atRA treatment to reduce proteinuria could be
      due to the increase in TGF-beta1 levels and to inhibition of iNOS-driven NO
      production.

PMID- 11831440
TI  - Transient exposure of human bronchial epithelial cells to cytokines leads to
      persistent increased expression of ICAM-1.
AB  - Effects of several cytokines on kinetics of Intercellular Adhesion Molecule-1
      (ICAM-1) and Vascular Cell Adhesion Molecule-1 (VCAM-1) expression were studied
      on a bronchial epithelial cell line (BEAS-2B). VCAM-I was neither constitutively
      expressed on BEAS-2B cells nor induced by Interferon-gamma (IFN-gamma). Tumor
      Necrosis Factor-alpha (TNF-alpha), Interleukin-1beta (IL-1beta), IFN-alpha, IL-4,
      IL-6, IL-8 or Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF). ICAM-1
      was constitutively expressed on BEAS-2B cells. IFN-gamma and TNF-alpha
      upregulated ICAM-1 expression on these cells. The functional importance of IFN
      gamma plus TNF-a upregulation of ICAM-1 expression on BEAS-2B cells was
      demonstrated by neutrophil-BEAS-2B cell adhesion assays. Cytokines are rapidly
      released and cleared in animals. Therefore, transient cytokine(s) exposure might
      occur on the bronchial mucosa. Brief incubation of BEAS-2B cells with IFN-gamma
      plus TNF-alpha led initial upregulation of ICAM-1 expression followed by a
      protracted downregulation. Our findings stress the importance of studying the
      mechanism(s) controlling the persistent increased expression of ICAM-1 after
      brief cytokine(s) exposure.

PMID- 11831441
TI  - Contribution of myeloperoxidase to coronary artery vasculitis associated with MPO
      ANCA production.
AB  - The role of myeloperoxidase (MPO) in the pathogenesis of vasculitis associated
      with MPO-specific anti-neutrophil cytoplasmic autoantibody (MPO-ANCA) was
      examined in a murine animal model. Coronary artery vasculitis was induced in
      C57BL/6 mice with and without endogenous MPO by intraperitoneal injection of
      Candida albicans-derived substances (CADS). The corresponding levels of MPO-ANCA
      in sera of mice with and without vasculitis were measured and compared in both
      wild-type and MPO-deficient animals. The MPO-ANCA titers in sera were
      significantly higher in mice with vasculitis than in vasculitis-negative mice,
      indicating that MPO-ANCA correlated with vasculitis formation. However, the
      increase of MPO-ANCA titers observed in sera of wild C57BL/6 mice were strongly
      suppressed in MPO-deficient C57BL/6 mice, accompanied with prevention of
      vasculitis formation. These results show that MPO acted as an antigen for MPO
      ANCA production by CADS and was followed by the vasculitis formation. Vasculitis
      did develop in a few MPO-deficient mice, though the incidence of vasculitis was
      much lower in MPO-deficient mice than in C57BL/6 mice.

PMID- 11831442
TI  - Immediate and delayed leukocyte apoptosis in two models of peritonitis.
AB  - Leukocyte apoptosis is an energy-dependent process that facilitates resolution of
      the cellular inflammatory response. Levels of apoptosis can be accelerated or
      inhibited after exposure to various stimuli. To compare apoptosis in
      transmigrated leukocytes, two models of peritonitis in mice were used that both
      cause leukocyte influx into the peritoneal cavity: (1) intraperitoneal
      thioglycollate administration producing a sterile peritonitis and (2) cecal
      ligation and puncture (CLP) producing a polymicrobial bacterial peritonitis.
      Samples of blood and peritoneal exudate cells (PEC) were collected at multiple
      time points after induction of peritonitis. Leukocytes were either fixed
      immediately to determine an immediate apoptosis level or cultured for 24 h to
      determine a delayed apoptosis level. Apoptosis was assessed using terminal
      uridine-triphosphate nick-end labeling (TUNEL) assay, flow cytometry, and
      confocal microscopy. Leukocyte influx into the peritoneal cavity was confirmed in
      both models. At all time points, and in both models, there was increased
      immediate apoptosis in PEC compared with unmanipulated controls and this increase
      was maximal in CLP after 18 h, although it appeared to remain at a stable level
      in the sterile peritonitis model by 3 h. There was also an increase in PEC
      delayed apoptosis at early time points in both models, again maximal at 18 h for
      CLP, with the levels being significantly higher than the thioglycollate model at
      6 h and 18 h. The mice had a relative peripheral neutropenia at 6 h after CLP,
      but not post thioglycollate injection, and this persisted until 42 h. Lung and
      liver MPO levels were elevated in CLP but did not increase after thioglycollate.
      There was no increase in immediate peripheral leukocyte apoptosis in either
      model, but an increase in delayed peripheral leukocyte apoptosis was observed by
      18 h in both models. Peripheral leukocyte CD1lb expression, which is a marker of
      activation, was also persistently elevated in the CLP model, but not in sterile
      peritonitis. In conclusion, CLP is a more potent stimulus for apoptosis of
      leukocytes than their migration to the site of inflammation alone, as occurs in
      the thioglycollate model. Blood leukocyte apoptosis also appears not to be
      dependent on CD11b expression, and therefore activation status.

PMID- 11831443
TI  - Increased expression of CD25 and HLA-DR on lymphocytes recruited into the
      peritoneal cavity in non-infected CAPD patients.
AB  - The impact of uremia per se, peritoneal dialysis (PD) and hemodialysis (HD)
      treatment was evaluated on characteristics of lymphocytes. CD4, CD8, CD25 and HLA
      DR were analyzed, with flow cytometry, in lymphocytes prepared from peripheral
      blood of uremic (n = 10) and hemodialysis patients (n = 10). Peritoneal dialysate
      was also obtained from patients on CAPD (n = 12). A decreased relative and
      absolute lymphocyte count was observed in peripheral blood from uremic, HD and
      CAPD patients compared to healthy controls (p < 0.03, p < 0.03 and p < 0.02,
      respectively). On the other hand, the relative distribution of lymphocytes was
      significantly higher in peritoneal dialysate compared to peripheral blood of CAPD
      patients (p < 0.02). Likewise, the absolute CD4 positive lymphocyte count was
      lower in the peripheral blood from uremic. HD and CAPD patients as compared to
      healthy controls (p < 0.001, respectively). In CAPD patients the relative
      distribution of CD4 positive cells (p < 0.001) was lower, while quantitative CD25
      level (p < 0.01) and the relative count of HLA-DR (p < 0.0001) was increased in
      the peritoneal dialysate compared to blood. Taken together a selective activation
      of lymphocytes in peritoneal dialysate as compared to peripheral blood from
      uremic, HD and CAPD patients was observed. The altered biological function of the
      inflammatory cells may therefore explain the increased susceptibility to
      infectious diseases.

PMID- 11831444
TI  - The cost of asthma treatment in Spain and rationalizing the expense.
AB  - According to Weiss et al. [12], the main providers of asthma care in the United
      States in 1992 were general and family medicine + internal medicine (46%),
      pediatrics (19%), allergy (25%), pulmonary medicine (5%), and others (5%). In an
      overall climate of a shift of referral from primary care to the specialties,
      specialists will have to provide evidence that their intervention in the control
      of patients provides truly better clinical and economical outcomes than that of
      general practitioners. In order to support this hypothesis, we estimated: (1) the
      development of the costs of medication for asthma in a population of 40 million
      people (Spain) and (2) the correlation between these costs and the intervention
      of a specialized attendance. In Spain the annual costs incurring from allergic
      diseases are estimated to be approximately 1,500 million Euros and, the cost due
      to asthma alone is about 900-1,200 million Euros. There are two main ways to
      explain the size of these figures. First, the prevalence of allergic diseases is
      rising year by year. Second, the relevance of allergology in the control of
      asthma is often greatly reduced. This has resulted in a reduction in the
      etiological diagnosis and treatment with specific immunotherapy (SIT). However,
      SIT is the only specific causal treatment of allergic asthma that is able to
      modify the natural history of disease or disease progression. So, it is possible
      to hypothesize that this reduction in a proper etiological diagnosis and
      treatment could be a cause (among others) of increasing costs.

PMID- 11831445
TI  - Safety and efficacy of specific immunotherapy with standardized allergenic
      extracts adsorbed on aluminium hydroxide.
AB  - Specific immunotherapy (SIT) with standardized allergenic extracts is the only
      specific treatment of allergic patients. In order to evaluate the safety, side
      effects, and efficacy of SIT with standardized extracts adsorbed to aluminium
      hydroxide manufactured by Stallergenes S.A., a prospective multicenter open study
      was performed in Switzerland. Fifteen patients suffering from seasonal or
      perennial rhinoconjunctivitis with or without asthma were included in the trial
      and received a total of 442 injections with standardized mix of grass pollens (n
      = 8) or house dust mites (n = 7) over one year. Low incidence of local reactions
      was noted (7%). Subcutaneous nodules (granuloma) following injections were not
      recorded. Only a few systemic reactions (one mild rhinitis, one mild asthma
      attack, one worsening of eczema) were recorded. No anaphylactic reactions
      requiring adrenaline were recorded. No admission to the hospital was required.
      Global appreciation of the physicians and the patients after the first year of
      treatment showed a good efficacy of SIT: Only two patients (13%) did not improve.
      A worsening of the symptoms was not observed. In order to assess the efficacy,
      skin reactivity and conjunctival reactivity to allergen challenge were compared
      before and after one year of treatment as well as immunologic parameters (such as
      specific IgE, specific IgG4) in blood samples. A significant decrease in skin
      reactivity (p = .001) and in conjunctival reactivity (p = .01) was observed.
      Specific IgE level decreased for both types of allergens but to a significantly
      greater extent for grass pollen allergen (p = .03). Specific IgG4 level increased
      significantly for grass (p = 0.01) and for mites (p = 0.04). Specific
      immunotherapy appears to be a valuable tool in the efficient management of the
      allergic respiratory diseases.

PMID- 11831446
TI  - Allergic disease and the infestation of Enterobius vermicularis in Swedish
      children 4-10 years of age.
AB  - BACKGROUND: The possible association between certain childhood infections and the
      propensity to develop allergic disease may include intestinal helminth
      infections. The experiences of such associations derive mainly from studies in
      tropical areas, and the results are not clear-cut. OBJECTIVE: To explore the
      association between Enterobius vermicularis and allergic disease in Swedish
      children 4 to 10 years of age. METHOD: The occurrence of E. vermicularis was
      examined by perianal tape tests in 70 allergic children recovered from a
      pediatric register of positive skin-prick tests. A nonallergic control group (n =
      102) was gathered from a cohort of children previously examined for the
      prevalence of E. vermicularis and allergic symptoms. RESULTS: In the allergic
      group 26 of the 70 cases (37%) had a positive tape-test for E. vermicularis,
      compared to 23 of the 102 cases (23%) in the nonallergic control group (p =
      .037). CONCLUSION: The results indicate that E. vermicularis could be more
      frequent in children with allergic disease as defined by allergic symptoms and a
      positive skin-prick test compared to nonallergic children, i. e., those without a
      history of allergic disease. These data, however, do not allow any conclusion on
      the nature of the possible association between E. vermicularis and allergic
      disease.

PMID- 11831447
TI  - Variation in skin reactivity inhalant allergens estimated by the end-point
      technique.
AB  - Skin prick testing is commonly used to diagnose IgE-mediated sensitization to
      allergens, whereas the longitudinal variability in positive/negative results can
      be used for clinical and epidemiological purposes. Few publications have
      investigated the longitudinal variability in skin reactivity, and most studies
      have concluded that seasonal changes in exposure to environmental allergens are
      paralleled by a change in skin reactivity. Our trial investigated the
      relationship between variations in skin reactivity and seasonal exposure to
      allergens in sensitized subjects, by use of a sensitive method-the end-point
      technique. Forty-three patients monosensitized to inhalant allergens were
      selected, and the skin prick end-point technique with serial 1:4 dilutions of
      standardized commercial allergens was used to assess skin reactivity. Twenty-two
      patients sensitized to pollens with a short pollination period were tested before
      and after the pollen season, whereas the other 21 patients sensitized to house
      dust mites or to a species with a long pollination period such as Parietaria were
      tested in the same month 12 months later. Patients tested with the end-point
      technique showed a large interindividual variability in skin reactivity. None of
      the patients in either group showed a decrease in skin sensitivity with time
      whereas 9 out of 43 showed no change and 34 out of 43 showed an increase (p <
      .0001). According to our data, skin reactivity increases in sensitized subjects
      over time, and this increase seems not to have a circannual rhythm related to the
      seasonal exposure to environmental allergens, since it can be detected both in
      pollen- and mite-sensitized patients after a 12-month interval.

PMID- 11831448
TI  - Immunotherapy units: a follow-up study.
AB  - Immunotherapy units are becoming an increasingly important component of allergy
      and clinical immunology departments in Spain. The objective of this study was to
      establish the rate of adverse reactions registered in an immunotherapy unit in
      Tenerife, Canary Islands, Spain, from May 1998 to May 2000. A total of 5,108
      immunotherapy doses were administered to 339 patients (123 males and 216
      females): 254 patients (75%) received mite, 48 patients (14.1%) pollen, 7
      patients (2%) cat, 2 patients (0.6%) Alternaria alternata, and 38 patients
      (11.2%) hymenoptera venom immunotherapy; 238 patients (70.2%) had
      rhinoconjunctivitis and asthma, 59 (17.4%) rhinoconjunctivitis, 5 (1.4%) asthma,
      and 38 (11.2) hymenoptera sensitivity. A total of 42 episodes of adverse
      reactions were recorded (0.8% of all the administered doses). Of these reactions,
      36 (85.7%) occurred within 30 minutes after the injection was administered,
      consisting of 15 large local reactions (0.3% of the total amount of injection
      given) and 21 systemic reactions (0.4%) that occurred only in asthmatic patients.
      All the systemic reactions were mild and rapidly reversible with appropriate
      treatment. Only in two cases was an immediate systemic reaction associated with a
      large local reaction. Six reactions (14.3%) occurred after 30 minutes and
      consisted only of large local reactions. A total of 15 systemic episodes (71.4%
      of all the systemic reactions) were registered at initial build-up doses. As to
      the types of allergens, 14.2% of the individuals receiving cat immunotherapy,
      7.8% of the individuals receiving hymenoptera venom, 6.3% of the individuals
      receiving pollen immunotherapy, and 2.7% of the individuals receiving mite
      immunotherapy experienced an adverse reaction. Only 0.8% of the administered
      doses presented any kind of adverse reaction, of which only 0.4% were systemic.
      The latter were always mild and rapidly reversible with adequate treatment, and
      there was no vital danger for any patient. Immunotherapy is a safe modality of
      treatment for allergic respiratory diseases and immunotherapy units provide a
      controlled and safe environment for its administration.

PMID- 11831449
TI  - No change in impaired cellular immune response of HIV-negative homosexuals after
      15 years of HIV epidemic in Eastern/Central European region.
AB  - Impaired cell-mediated immune reactivity to polyclonal mitogens was determined in
      HIV-negative homosexual men (HIV-MSM). Results were compared to those we reported
      in a complex clinical and immunological investigation in the same risk groups 15
      years ago, before the onset of the AIDS epidemic in Hungary. Cellular immune
      reactivity to polyclonal mitogens was studied in 74 HIV-infected or HIV
      uninfected homosexual men and heterosexual controls. Lymphocytes in whole-blood
      cultures were stimulated with various doses of phytohaemagglutinin (PHA),
      concanavalin-A (Con-A), and pokeweed mitogen (PWM) in a blast transformation
      assay. A significant difference (p = .0002) in lymphocyte proliferation between
      HIV-MSM vs. heterosexuals using PWM in both concentrations was found.
      Proliferative capacity was similar in HIV- MSM and HIV infected males with CD4+ >
      500/microl. Con-A and PHA showed a less expressed proliferative response.
      Decreased lymphocyte reactivity to PWM, similar to the one in early HIV
      infection, could be observed in HIV-MSM. This HIV-independent mild
      immunodeficiency in MSM is a sign of an increased susceptibility and predisposes
      to subsequent HIV infection. It seems, however, that MSM's impaired immune
      response observed over a period of 15 years is an immunodeficiency not changed by
      the emerging HIV/AIDS epidemic. Our study provides an explanation why the
      incidence of new HIV cases in homo-/bisexual individuals is still high (> 70%),
      and it indicates that it remains high in Hungary.

PMID- 11831450
TI  - Tachyphylaxis following regular use of formoterol in exercise-induced
      bronchospasm.
AB  - BACKGROUND: Formoterol is a highly effective therapeutic agent in the prevention
      of exercise-induced bronchospasm (EIB). Regular use of beta-adrenergic drugs may
      result in a reduction in the protective effect afforded by these bronchodilators
      against bronchoconstrictor stimuli. It is unknown whether this effect extends to
      formoterol and exercise. METHODS: We performed a randomized, double-blind,
      parallel clinical trial in 19 patients with EIB. Each patient received inhaled
      formoterol or placebo twice daily during 4 weeks. Patients performed two exercise
      tests in a cycle ergometer on the 1st, 14th, and 28th study days separated 3
      hours from each other. A dose of formoterol was given 30 min prior to the 2nd
      test. RESULTS: There were significant differences in bronchoprotection between
      days 1 and 14 (p = .012) and between days 1 and 28 (p = .012) in the formoterol
      group. No differences were found in the placebo group. The evolution of the
      bronchoprotection index was also significantly different between the formoterol
      and the placebo group (p = .002) from day 1 to 28. CONCLUSIONS: Tachyphylaxis
      developed to the protective effect of formoterol against EIB after 4 weeks of
      regular dosing. Tolerance was already found on day 14, though not progressive.
      Formoterol should be recommended only as needed in EIB.

PMID- 11831451
TI  - Month of birth, atopic disease, and atopic sensitization.
AB  - BACKGROUND: Japanese cedar (Cryptmeria japonica; CJ) pollen and house dust mites
      are the two important aeroallergens in Japan. However, no epidemiological survey
      has been performed in Japan to investigate the relationship between month of
      birth and manifestations of allergic disease and sensitization. OBJECTIVE: This
      study evaluates the correlation between month of birth and sensitization to
      aeroallergens or the occurrence of allergic disease on 755 Japanese school
      children aged 12-13 years. METHODS: The personal history of atopic disease
      (bronchial asthma, allergic rhinitis, eczema, and allergic conjunctivitis) as
      recorded by questionnaires was investigated in relation to total serum IgE and
      specific IgE toward house dust mites and CJ pollen. RESULTS: Positive specific
      IgE toward house dust mites was significantly less prevalent in the children born
      between January and March than those born during the rest of the year (p < 0.01).
      Positive specific IgE toward CJ pollen was significantly more prevalent in the
      children born between December and January than those born during the rest of the
      year (p < 0.05). High total IgE was less prevalent in the children born between
      February and April than in children born during the rest of the year (p = 0.05).
      The prevalence of bronchial asthma was 26.2% among children born between November
      and December, compared with a ratio of 17.3% among children born during the rest
      of the year (p < 0.05). A significantly higher proportion of the children with
      allergic rhinitis was born between August and October than during the rest of the
      year (p < 0.05). The prevalence of allergic conjunctivitis was 15.8% among the
      children who were born between December and January, compared with 9.1% among
      children born during the rest of the year (p < 0.01). No relationship between
      prevalence of eczema and season of birth was found. CONCLUSION: Month of birth
      appears to influence the risk in the development of allergic sensitization and
      atopic diseases. The findings concerning higher CJ pollen sensitization in
      children born in the months that proceed the CJ pollen seasons are as evident as
      the house-dust-mite-related findings.

PMID- 11831452
TI  - Influence of inhaled steroids on pulmonary epithelial permeability to Tc99m-dTPA
      in atopic asthmatic children.
AB  - The lung permeability of asthmatic children has been reported to be similar,
      lower, or higher than that of healthy subjects. The aim of this study was to
      clarify these discrepancies and also assess the effect of inhaled steroids on
      lung permeability. Tc99m-diethylenetriaminepentaaceticacid (Tc99m-DTPA) clearance
      in children with mild unstable asthma (n = 13; mean age 9.3 +/- 0.7 years) was
      compared with that of a group of healthy subjects (n = 11; mean age 8.9 +/- 0.8
      years). Symptom scores, forced-expiratory volume in the first second (FEV1), and
      peak expiratory flow rate variability (PEFR-v) of asthmatics were recorded and an
      inhaled steroid (budesonid) was recommended after first scintigraphic evaluation
      for 8 weeks. Two consecutive scintigraphic studies were performed before and
      after treatment. Symptoms, FEV1, and PEFR-v significantly improved throughout the
      study. Baseline DTPA clearance rate in the asthmatics was significantly higher
      from that of control group (1.3 +/- 0.2 and 0.7 +/- 0.1%/min, respectively) (p <
      0.05). DTPA clearance rate of asthmatics significantly increased to 1.7 +/-
      0.3%/min at end of inhaled therapy (p < 0.05). Our data show that DTPA clearance
      in unstable asthmatic children is significantly higher than that found in healthy
      subjects, and that a higher rate was obtained following inhaled steroid therapy.
      Thus, the clinical significance of these observations needs further studies to
      test whether DTPA clearance index is a valid tool for monitoring asthmatic
      children and to explore the mechanisms involved in radioaerosol clearance rates
      in pediatric asthma.

PMID- 11831453
TI  - Variants of endothelin-1 gene in atopic diseases.
AB  - BACKGROUND: Several studies suggest that the vasoactive peptide endothelin-1 (ET
      1) could be involved in the pathophysiology of atopic asthma and allergic
      rhinitis. However, a possible involvement of polymorphisms of the corresponding
      gene in the origin of these conditions has so far not been subjected to a more
      comprehensive study. OBJECTIVE: This study investigates a possible association of
      two common polymorphisms in the ET-1 gene (TaqI in intron4 and BsiYI in position
      138) with clinically manifested atopic diseases. The genetic linkage of these
      polymorphisms with the underlying phenotypes of asthma or parameters of atopy
      including total IgE level was examined, too. METHODS: The study included 456
      subjects-270 Czech patients (Caucasians, Central Europe) with clinically
      manifested atopic diseases and 186 unrelated referent subjects with negative
      familial history of asthma/atopy. ET-1 genotypes were determined by PCR and
      restriction analysis by TaqI and BsiYI, respectively. RESULTS: No significant
      differences were found for the two polymorphisms between atopic patients and
      healthy subjects, or between subselected asthmatic patients and controls.
      However, the insertion exonic variant of ET-1 gene showed a significant
      association with signs of atopy, especially with total serum IgE levels (total
      IgE levels < or = 150 IU/ml turned out to be associated with DD genotypes, total
      IgE > 150 IU/ml with II and ID genotypes [OR = 3.76 (95% CI: 1.52-9.34), p =
      0.003, Pc = 0.0061). CONCLUSIONS: These findings suggest that ET-1 may
      participate in the pathogenesis of high total serum IgE level in clinically
      manifested atopic diseases in our population.

PMID- 11831454
TI  - Asthma from inhalation of Triplochiton scleroxylon (Samba) wood dust.
AB  - The inhalation of wood dust may produce allergic rhinitis, asthma, or contact
      dermatitis in sensitized patients. We describe a patient with occupational asthma
      induced by the inhalation of samba (Triplochiton scleroxylon) wood dust. A
      specific bronchial provocation test was conducted, and the patient showed a
      significant decrease in forced-expiratory volume in first second (FEV1) after the
      inhalation of nebulized samba wood allergens. We suggest an IgE-mediated
      mechanism since the patient had a positive skin test and positive specific IgE
      determinations using an extract of samba wood. SDS-PAGE immunoblots revealed IgE
      binding to proteins with molecular weights of 17 kDa, 28 kDa and less intense
      binding to a band with an approximate molecular weight of 60 kDa. Two
      asymptomatic skin test-negative subjects, also occupationally exposed to samba,
      did not show any signs of bronchoconstriction when challenged with the samba wood
      extracts. We conclude that the occupational asthma suffered by this patient is
      related to sensitization and occupational exposure to samba wood dust.

PMID- 11831455
TI  - Usefulness of patch tests for diagnosing selective allergy to captopril.
AB  - Captopril, enalapril, and lisinopril are angiotensin-converting enzyme (ACE)
      inhibitors widely prescribed for hypertension and heart failure. Cutaneous side
      effects of captopril include angio-edema, anaphylactoid reactions, maculopapular
      eruptions, pitiryasis rosea-like rash, toxic erythema, and exfoliative
      dermatitis. Some of the immunological captopril-induced cutaneous adverse
      reactions have been diagnosed in recent years by patch tests. A case of a
      cutaneous immune adverse reaction to captopril with tolerance to enalapril and
      lisinopril demonstrated both by patch tests and double-blind challenge tests is
      reported for the first time. A 71-year-old nonatopic woman suffered a generalized
      pruriginous maculopapular rash. Two months earlier, she had started oral
      treatment with captopril 50 mg t.i.d and glibenclamide 5 mg daily. After the rash
      appeared, she stopped both drugs and the reaction cleared. A skin biopsy from one
      of the lesions showed perivascular lymphocytic infiltrate of the upper dermis.
      Skin prick tests with captopril and glibenclamide and patch tests with enalapril,
      lisinopril, and glibenclamide at 1% and 10% pet., and with mercaptobenzothiazole
      (a sulfhydryl group-containing chemical at 1% pet were negative. Only patch tests
      with captopril at 1% and 10% concentrations were positive at 48 h. Oral double
      blind challenge tests with glibenclamide, enalapril, lisinopril, and placebo
      showed good tolerance. The patient was advised to avoid only captopril. Because
      captopril is the only ACE inhibitor containing a sulfhydryl group and has
      occasionally been implicated in complex immunological diseases, this chemical
      group has been considered the culprit of allergic reactions to captopril. The
      lack of cross-reactivity between captopril, enalapril, and benazepril has been
      demonstrated in a few patients by patch tests. In our patient, patch tests
      identified captopril as the drug responsible for a probably immune adverse
      reaction not due to the sulfhydryl group. Patch tests are useful and safe in the
      diagnostic work-up of allergic drug reactions and in studies of cross-sensitivity
      among ACE inhibitors.

PMID- 11831456
TI  - Chemistry of zinc(II) fluorophore sensors.
AB  - The biological role of the zinc(II) ion has been recognized in DNA and RNA
      synthesis, apoptosis, gene expression, or protein structure and function.
      Therefore, development of useful zinc(II) sensors has recently been attracting
      much interest. Chemistry for selective and efficient detection of trace Zn2+ is a
      central issue. Recently, various types of zinc-fluorophores are emerging,
      comprising bio-inspired aromatic sulfonamide derivatives, zinc-finger peptides
      attached to fluorescent dyes, or fluorophore-pendant macrocyclic polyamines. The
      chemical principles, properties and limitations of these Zn2+-fluorophores are
      discussed.

PMID- 11831457
TI  - Fluorescence-based biosensing of zinc using carbonic anhydrase.
AB  - Measurement of free zinc levels and imaging of zinc fluxes remains technically
      difficult due to low levels and the presence of interfering cations such as Mg
      and Ca. We have developed a series of fluorescent zinc indicators based on the
      superb sensitivity and selectivity of a protein, human apo-carbonic anhydrase II,
      for Zn(II). These indicators transduce the level of free zinc as changes in
      intensity, wavelength ratio, lifetime, and/or anisotropy; the latter three
      approaches permit quantitative imaging of zinc levels in the microscope. A unique
      attribute of sensors incorporating biological macromolecules as transducers is
      their capability for modification by site-directed mutagenesis. Thus we have
      produced variants of carbonic anhydrase with improved affinity for zinc, altered
      selectivity, and enhanced binding kinetics, all of which are difficult to modify
      in small molecule indicators.

PMID- 11831458
TI  - Cellular zinc sensors: MTF-1 regulation of gene expression.
AB  - Zinc metabolism in higher eukaryotes is complex, being controlled by uptake,
      efflux, and storage in individual cells, as well as in peripheral tissues and
      organs. Recently there have been advances in the understanding of the genes
      involved in these processes and their regulation. Metal-response element-binding
      transcription factor-1 (MTF-1) functions as a cellular zinc sensor which
      coordinates the expression of genes involved in zinc homeostasis, as well as
      protection against metal toxicity and oxidative stresses. In mice, these are
      known to include the metallothionein (MT), the zinc-transporter-1 (ZnT1) and the
      gamma-glutamylcysteine synthetase heavy chain (gammaGCShc) genes. The cysteine
      rich MTs function as an intracellular metal-chelators that bind zinc with high
      affinity, whereas the transmembrane protein ZnT1 exports zinc from the cell.
      Gamma-glutamylcysteine synthetase controls the rate limiting step in glutathione
      (GSH) biosynthesis. GSH, which is present in mM concentrations in cells,
      effectively chelates large amounts of zinc in vitro. Both MT and GSH also
      function as antioxidants. The current model suggests that the zinc-finger domain
      of MTF-1 directly (and reversibly) binds to zinc. This metalloregulatory protein
      then adopts a DNA-binding conformation and translocates to the nucleus, where it
      binds to metal-response elements in these gene promoters leading to increased
      transcription. The six zinc-finger domain of this factor is highly conserved from
      insects to mammals, and biochemical studies confirm that the zinc-fingers are
      heterogeneous in function and in zinc-binding. Furthermore, the mouse MTF-1 gene
      is essential for development of the embryo, thus underscoring the importance of
      this transcription factor.

PMID- 11831459
TI  - Bacterial zinc transporters and regulators.
AB  - Zn2+ homeostasis in bacteria is achieved by export systems and uptake systems
      which are separately regulated by their own regulators. Three types of Zn2+
      export systems that protect cells from high toxic concentrations of Zn2+ have
      been identified: RND multi-drug efflux transporters, P-type ATPases, and cation
      diffusion facilitators. The RND type exporters for Zn2+ are only found in a few
      gram-negative bacteria; they allow a very efficient export across the cytoplasmic
      membrane and the outer membrane of the cell. P-type ATPases and cation-diffusion
      facilitators belong to protein families that are also found in eukaryotes. The
      exporters are regulated in bacteria by MerR-like repressor/activators or by ArsR
      like repressors. For the high-affinity uptake of Zn2+, several binding-protein
      dependent ABC transporters belonging to one class have been identified in
      different bacteria. Zn2+ ABC transporters are regulated by Zur repressors, which
      belong to the Fur protein family of iron regulators. Little is known about low
      affinity Zn2+ uptake under zinc-replete conditions. One known example is the
      phosphate uptake system Pit, which may cotransport Zn2+ in Escherichia coli.
      Similarly, the citrate-metal cotransporter CitM in Bacillus subtilis may help to
      supply Zn2+.

PMID- 11831460
TI  - Eukaryotic zinc transporters and their regulation.
AB  - The last ten years have witnessed major advances in our understanding of zinc
      transporters and their regulation in eukaryotic organisms. Two families of
      transporters, the ZIP (Zrt-, Irt-like Protein) and CDF (Cation Diffusion
      Facilitator) families, have been found to play a number of important roles in
      zinc transport. These are ancient gene families that span all phylogenetic
      levels. The characterized members of each group have been implicated in the
      transport of metal ions, frequently zinc, across lipid bilayer membranes. This
      remarkable conservation of function suggests that other, as yet uncharacterized
      members of the family, will also be involved in metal ion transport. Many of the
      ZIP family transporters are involved in cellular zinc uptake and at least one
      member, the Zrt3 transporter of S. cerevisiae, transports stored zinc out of an
      intracellular compartment during adaptation to zinc deficiency. In contrast, CDF
      family members mediate zinc efflux out of cells or facilitate zinc transport into
      intracellular compartments for detoxification and/or storage. The activity of
      many of these transporters is regulated in response to zinc through
      transcriptional and post-transcriptional mechanisms to maintain zinc homeostasis
      at both the cellular and organismal levels.

PMID- 11831461
TI  - Zinc coordination sphere in biochemical zinc sites.
AB  - Zinc is known to be indispensable to growth and development and transmission of
      the genetic message. It does this through a remarkable mosaic of zinc binding
      motifs that orchestrate all aspects of metabolism. There are now nearly 200 three
      dimensional structures for zinc proteins, representing all six classes of enzymes
      and covering a wide range of phyla and species. These structures provide
      standards of reference for the identity and nature of zinc ligands in other
      proteins for which only the primary structure is known. Three primary types of
      zinc sites are apparent from examination of these structures: structural,
      catalytic and cocatalytic. The most common amino acids that supply ligands to
      these sites are His, Glu, Asp and Cys. In catalytic sites zinc generally forms
      complexes with water and any three nitrogen, oxygen and sulfur donors with His
      being the predominant amino acid chosen. Water is always a ligand to such sites.
      Structural zinc sites have four protein ligands and no bound water molecule. Cys
      is the preferred ligand in such sites. Cocatalytic sites contain two or three
      metals in close proximity with two of the metals bridged by a side chain moiety
      of a single amino acid residue, such as Asp, Glu or His and sometimes a water
      molecule. Asp and His are the preferred amino acids for these sites. No Cys
      ligands are found in such sites. The scaffolding of the zinc sites is also
      important to the function and reactivity of the bound metal. The influence of
      zinc on quaternary protein structure has led to the identification of a fourth
      type of zinc binding site, protein inteface. In this case zinc sites are formed
      from ligands supplied from amino acid residues residing in the binding surface of
      two proteins. The resulting zinc site usually has the coordination properties of
      a catalytic or structural zinc binding site.

PMID- 11831462
TI  - The role of zinc in caspase activation and apoptotic cell death.
AB  - In addition to its diverse role in many physiological systems, zinc (Zn) has now
      been shown to be an important regulator of apoptosis. The purpose of this review
      is to integrate previously published knowledge on Zn and apoptosis with current
      attempts to elucidate the mechanisms of action of this biometal. This paper
      begins with an introduction to apoptosis and then briefly reviews the evidence
      relating Zn to apoptosis. The major focus of this review is the mechanistic
      actions of Zn and its candidate intracellular targets. In particular, we examine
      the cytoprotective functions of Zn which suppress major pathways leading to
      apoptosis, as well as the more direct influence of Zn on the apoptotic
      regulators, especially the caspase family of enzymes. These two mechanisms are
      closely related since a decline in intracellular Zn below a critical threshold
      level may not only trigger pathways leading to caspase activation but may also
      facilitate the process by which the caspases are activated. Studies by our
      laboratory in airway epithelial cells show that Zn is co-localized with the
      precursor form of caspase-3, mitochondria and microtubules, suggesting this Zn is
      critically placed to control apoptosis. Further understanding the different pools
      of Zn and how they interact with apoptotic pathways should have importance in
      human disease.

PMID- 11831463
TI  - Functions of zinc in signaling, proliferation and differentiation of mammalian
      cells.
AB  - Zinc is essential for cell proliferation and differentiation, especially for the
      regulation of DNA synthesis and mitosis. On the molecular level, it is a
      structural constituent of a great number of proteins, including enzymes of
      cellular signaling pathways and transcription factors. Zinc homeostasis in
      eukaryotic cells is controlled on the levels of uptake, intracellular
      sequestration in zinc storing vesicles ('zincosomes'), nucleocytoplasmic
      distribution and elimination. These processes involve the major zinc binding
      protein metallothionein as a tool for the regulation of the cellular zinc level
      and the nuclear translocation of zinc in the course of the cell cycle and
      differentiation. In addition, there is also increasing evidence for a direct
      signaling function for zinc on all levels of signal transduction. Zinc can
      modulate cellular signal recognition, second messenger metabolism, protein kinase
      and protein phosphatase activities, and it may stimulate or inhibit activities of
      transcription factors, depending on the experimental systems studied. Zinc has
      been shown to modify specifically the metabolism of cGMP, the activities of
      protein kinase C and mitogen activated protein kinases, and the activity of
      transcription factor MTF-1 which controls the transcription of the genes for
      metallothionein and the zinc transporter ZnT-1. As a conclusion of these
      observations new hypotheses regarding regulatory functions of zinc ions in
      cellular signaling pathways are proposed.

PMID- 11831464
TI  - Zinc homeostasis and functions of zinc in the brain.
AB  - The brain barrier system, i.e., the blood-brain and blood-cerebrospinal fluid
      barriers, is important for zinc homeostasis in the brain. Zinc is supplied to the
      brain via both barriers. A large portion of zinc serves as zinc metalloproteins
      in neurons and glial cells. Approximately 10% of the total zinc in the brain,
      probably ionic zinc, exists in the synaptic vesicles, and may serve as an
      endogenous neuromodulator in synaptic neurotransmission. The turnover of zinc in
      the brain is much slower than in peripheral tissues such as the liver. However,
      dietary zinc deprivation affects zinc homeostasis in the brain. Vesicular zinc
      enriched regions, e.g., the hippocampus, are responsive to dietary zinc
      deprivation, which causes brain dysfunctions such as learning impairment and
      olfactory dysfunction. Olfactory recognition is reversibly disturbed by the
      chelation of zinc released from amygdalar neuron terminals. On the other hand,
      the susceptibility to epileptic seizures, which may decrease vesicular zinc, is
      also enhanced by zinc deficiency. Therefore, zinc homeostasis in the brain is
      closely related to neuronal activity. Even in adult animals and probably adult
      humans, adequate zinc supply is important for brain functions and prevention of
      neurological diseases.

PMID- 11831465
TI  - Synaptically released zinc: physiological functions and pathological effects.
AB  - In addition to its familiar role as a component of metalloproteins, zinc is also
      sequestered in the presynaptic vesicles of a specialized type of neurons called
      'zinc-containing' neurons. Here we review the physiological and pathological
      effects of the release of zinc from these zinc-containing synaptic terminals. The
      best-established physiological role of synaptically released zinc is the tonic
      modulation of brain excitability through modulation of amino acid receptors;
      prominent pathological effects include acceleration of plaque deposition in
      Alzheimer's disease and exacerbation of excitotoxic neuron injury. Synaptically
      released zinc functions as a conventional synaptic neurotransmitter or
      neuromodulator, being released into the cleft, then recycled into the presynaptic
      terminal. Beyond this, zinc also has the highly unconventional property that it
      passes into postsynaptic neurons during synaptic events, functioning analogously
      to calcium in this regard, as a transmembrane neural signal. To stimulate
      comparisons of zinc signals with calcium signals, we have compiled a list of the
      important parameters of calcium signals and zinc signals. More speculatively, we
      hypothesize that zinc signals may loosely mimic phosphate 'signals' in the sense
      that signal zinc ions may commonly bind to proteins in a lasting manner (i.e.,
      'zincylating' the proteins) with consequential changes in protein structure and
      function.

PMID- 11831466
TI  - Extracellular and immunological actions of zinc.
AB  - Zinc is an essential trace element for the immune system, but also very important
      in other organ systems. Every highly proliferating cell system is dependent on
      sufficient availability of zinc. During the last decades the influence of zinc on
      various cell systems have been investigated. Multiple effects of exogenously
      added zinc have been described in in vitro culture systems and in in vivo
      systems. However, most of these effects are so far poorly understood, and the
      dosages used in the in vitro systems are not comparable and sometimes
      unphysiologically high. Especially in the immune system a number of effects were
      described and over the last ten years we have come to understand some molecular
      mechanisms of zinc in this cell system. A zinc deficiency is accompanied by an
      immunodeficiency, resulting in an increased number of infections. However, the
      immune function is delicately regulated by zinc, since both increased and
      decreased zinc levels result in a disturbed immune function. Therefore, zinc
      supplementation must be accurately supervised. In this review, we discuss the
      activity of extracellular zinc in four sections. 1. The effect of zinc on
      different in vitro cell systems, including keratinocytes, osteocytes and
      leukocytes, and the concentrations of zinc needed for a specific cell response.
      2. The modulation of the innate immune system in vitro and in vivo. 3. The role
      of zinc in the B cell response and antibody production. 4. Effects of zinc on the
      development and function of T cells.

PMID- 11831467
TI  - Zinc physiology and biochemistry in oocytes and embryos.
AB  - The essential role of zinc in embryogenesis was identified through studies of its
      presence in eggs and embryos, the effects of its deficiency and its role in
      metallo proteins required for organ development and formation. The Xenopus laevis
      oocyte zinc content varies during oogenesis. It increases from 3 to 70 ng
      zinc/oocyte as it progresses from stage I to VI. The oocyte zinc is derived from
      the maternal liver as part of a metallo-complex with vitellogenin. The latter
      transports the metal in plasma and into the oocyte. Once internalized, most of
      the zinc is stored within yolk platelets bound to lipovitellin, one of the
      processed products of vitellogenin. About 90% of the total zinc is associated
      with the yolk platelet lipovitellin while the remaining 10% is in a compartment
      associated with hitherto unknown molecule(s) or organelle(s) of the cytoplasm.
      The bi-compartmental distribution remains constant throughout embryogenesis since
      the embryo behaves as a closed system for zinc after fertilization. The yolk
      platelet zinc is used after the tadpole is hatched while we proposed that the 10%
      of the zinc in the non-yolk platelet pool is the one used for embryogenesis. It
      provides zinc to newly synthesized molecules responsible for the development of
      zinc-dependent organ genesis. Interference with the availability of this zinc by
      the chelating agent 1,10-phenanthroline results in the development of embryos
      that lack dorsal organs, including brain, eyes and spinal cord. The extensive
      teratology is proposed to be due to altered or absent zinc distribution between
      the cytosolic pool and zinc-transcription factors. The data identify the
      components of a zinc transport, storage and distribution system in a vertebrate
      organism.

PMID- 11831468
TI  - Zinc metabolism and homeostasis: the application of tracer techniques to human
      zinc physiology.
AB  - Tracer kinetic techniques based on zinc stable isotopes have a vital role in
      advancing knowledge of human zinc physiology and homeostasis. These techniques
      have demonstrated the complexity of zinc metabolism, and have been critical to
      estimating the size and interrelationships of those pools of zinc that exchange
      rapidly with zinc in plasma and which are likely to be especially important for
      zinc dependent biology. This paper presents findings from recent research linking
      a steady state compartmental model with non-steady state post-prandial sampling
      from the intestine, utilizing a combination of intestinal intubation/perfusion
      and stable isotope tracer kinetic techniques. The gastrointestinal tract has a
      central role in maintaining whole body zinc homeostasis. While the fractional
      absorption of zinc from a meal depends on the quantity of exogenous zinc and on
      such dietary factors as phytic acid, the fractional absorption does not appear to
      be dependent on the size of the rapidly exchanging pool of the host. In contrast,
      the quantity of endogenous zinc excreted via the intestine is positively
      correlated with both the amount of absorbed zinc and the zinc 'status' of the
      host, and thus this process has an equally critical role in maintaining zinc
      homeostasis. The observed alterations in zinc metabolism in some disease states
      can be understood in the context of known homeostatic processes. In other
      conditions, however, such alterations as inflammation-associated hyperzincuria
      and zinc redistribution, the links between homeostatic perturbation and cellular
      biology are yet to be explained. Thus the challenge remains for research at the
      whole body level to carefully characterize zinc distribution and exchange under
      diverse circumstances, while research at the cellular level must elucidate the
      regulatory processes and the factors to which they respond.

PMID- 11831469
TI  - Biotechnologically relevant enzymes from Thermus thermophilus.

PMID- 11831470
TI  - Selective enrichment and characterization of a phosphorus-removing bacterial
      consortium from activated sludge.
AB  - Under alternating aerobic/anaerobic conditions and without additional carbon
      sources, a bacterial consortium consisting initially of 18 bacterial strains was
      obtained in a sequence batch reactor. The phosphorus removal capability could
      only be maintained using sterile filtrate of activated sludge as medium. The
      addition of calcium and magnesium salts, as well as vitamins and trace elements,
      to autoclaved sterile filtrate of activated sludge was not sufficient to achieve
      stable phosphorus removal. A further enrichment by subcultivation on solid, agar,
      freezing, and shortening of the aerobic and anaerobic phases led to a defined
      bacterial consortium consisting of four strains. On the basis of physiological
      and chemotaxonomic characterization, and partial 16S rRNA sequencing, one of the
      organisms was identified as Delftia acidovorans. A further isolate belonged to
      the Bacillus cereus group, and the third isolate was identified as Microbacterium
      sp.. The remaining strain seems to represent a new genus within the
      Flavobacteriaceae. Under continuous chemostat conditions, this consortium was
      able to remove up to 9.6 mg P/l phosphate in the aerobic phase and released up to
      8.5 mg/l in the anaerobic phase. Up to 25 mg P-polyphosphate/g dry mass was
      stored under aerobic conditions.

PMID- 11831471
TI  - Quinoproteins: structure, function, and biotechnological applications.
AB  - A new class of oxidoreductase containing an amino acid-derived o-quinone
      cofactor, of which the most typical is pyrroloquinoline quinone (PQQ), is called
      quinoproteins, and has been recognized as the third redox enzyme following
      pyridine nucleotide- and flavin-dependent dehydrogenases. Some quinoproteins
      include a heme c moiety in addition to the quinone cofactor in the molecule and
      are called quinohemoproteins. PQQ-containing quinoproteins and quinohemoproteins
      have a common structural basis, in which PQQ is deeply embedded in the center of
      the unique superbarrel structure. Increased evidence for the structure and
      function of quinoproteins has revealed their unique position within the redox
      enzymes with respect to catalytic and electron transfer properties, and also to
      physiological and energetic function. The peculiarities of the quinoproteins,
      together with their unique substrate specificity, have encouraged their
      biotechnological application in the fields of biosensing and bioconversion of
      useful compounds, and also to environmental treatment.

PMID- 11831472
TI  - Biosynthesis, biotechnological production and applications of 5-aminolevulinic
      acid.
AB  - Microbial production of 5-aminolevulinic acid (ALA) by photosynthetic bacteria
      compared to other bacteria and algae is reviewed. During aerobic-microaerobic
      cultivation of Rhodobacter sphaeroides mutant strain CR520, control of the redox
      potential was effective for producing large amounts of extracellular ALA. ALA has
      been practically applied in agriculture as an herbicide, an insecticide and a
      growth-promoting factor for plants. New agricultural applications including salt
      tolerance and cold temperature tolerance of plants are also described. Finally,
      recent medical applications for cancer treatment, tumor diagnosis and other
      clinical uses are discussed.

PMID- 11831473
TI  - Microbial degradation of polyethers.
AB  - This paper summarizes studies on microbial degradation of polyethers. Polyethers
      are aerobically metabolized through common mechanisms (oxidation of terminal
      alcohol groups followed by terminal ether cleavage), well-characterized examples
      being found with polyethylene glycol (PEG). First the polymer is oxidized to
      carboxylated PEG by alcohol and aldehyde dehydrogenases and then the terminal
      ether bond is cleaved to yield the depolymerized PEG by one glycol unit. Most
      probably PEG is anaerobically metabolized through one step which is catalyzed by
      PEG acetaldehyde lyase, analogous to diol dehydratase. Whether aerobically or
      anaerobically, the free OH group is necessary for metabolization of PEG. PEG with
      a molecular weight of up to 20,000 was metabolized either in the periplasmic
      space (Pseudomonas stutzeri and sphingomonads) or in the cytoplasm (anaerobic
      bacteria), which suggests the transport of large PEG through the outer and inner
      membranes of Gram-negative bacterial cells. Membrane-bound PEG dehydrogenase (PEG
      DH) with high activity towards PEG 6,000 and 20,000 was purified from PEG
      utilizing sphingomonads. Sequencing of PEG-DH revealed that the enzyme belongs to
      the group of GMC flavoproteins, FAD being the cofactor for the enzyme. On the
      other hand, alcohol dehydrogenases purified from other bacteria that cannot grow
      on PEG oxidized PEG. Cytoplasmic NAD-dependent alcohol dehydrogenases with high
      specificity towards ether-alcohol compound, either crude or purified, showed
      appreciable activity towards PEG 400 or 600. Liver alcohol dehydrogenase (equine)
      also oxidized PEG homologs, which might cause fatal toxic syndrome in vivo by
      carboxylating PEG together with aldehyde dehydrogenase when PEG was absorbed. An
      ether bond-cleaving enzyme was detected in PEG-utilizing bacteria and purified as
      diglycolic acid (DGA) dehydrogenase from a PEG-utilizing consortium. The enzyme
      oxidized glycolic acid, glyoxylic acid, as well as PEG-carboxylic acid and DGA.
      Similarly, dehydrogenation on polypropylene glycol (PPG) and polytetramethylene
      glycol (PTMG) was suggested with cell-free extracts of PPG and PTMG-utilizing
      bacteria, respectively. PPG commercially available is atactic and includes many
      structural (primary and secondary alcohol groups) and optical (derived from
      pendant methyl groups on the carbon backbone) isomers. Whether PPG dehydrogenase
      (PPG-DH) has wide stereo- and enantioselective substrate specificity towards PPG
      isomers or not must await further purification. Preliminary research on PPG-DH
      revealed that the enzyme was inducibly formed by PPG in the periplasmic, membrane
      and cytoplasm fractions of a PPG-utilizing bacterium Stenotrophomonas
      maltophilia. This finding indicated the intracellular metabolism of PPG is the
      same as that of PEG. Besides metabolization of polyethers, a biological Fenton
      mechanism was proposed for degradation of PEG, which was caused by extracellular
      oxidants produced by a brown-rot fungus in the presence of a reductant and Fe3+,
      although the metabolism of fragmented PEG has not yet been well elucidated.

PMID- 11831474
TI  - Biodegradation of atrazine and related s-triazine compounds: from enzymes to
      field studies.
AB  - s-Triazine ring compounds are common industrial chemicals: pesticides, resin
      intermediates, dyes, and explosives. The fate of these compounds in the
      environment is directly correlated with the ability of microbes to metabolize
      them. Microbes metabolize melamine and the triazine herbicides such as atrazine
      via enzyme-catalyzed hydrolysis reactions. Hydrolytic removal of substituents on
      the s-triazine ring is catalyzed by enzymes from the amidohydrolase superfamily
      and yields cyanuric acid as an intermediate. Cyanuric acid is hydrolytically
      processed to yield 3 mol each of ammonia and carbon dioxide. In those cases
      studied, the genes underlying the hydrolytic reactions are localized to large
      catabolic plasmids. One such plasmid, pADP-1 from Pseudomonas sp. ADP, has been
      completely sequenced and contains the genes for atrazine catabolism. Insertion
      sequence elements play a role in constructing different atrazine catabolic
      plasmids in different bacteria. Atrazine chlorohydrolase has been purified to
      homogeneity from two sources. Recombinant Escherichia coli strains expressing
      atrazine chlorohydrolase have been constructed and chemically cross-linked to
      generate catalytic particles used for atrazine remediation in soil. The method
      was used for cleaning up a spill of 1,000 pounds of atrazine to attain a level of
      herbicide acceptable to regulatory agencies.

PMID- 11831476
TI  - Evaluation of an endo-beta-mannanase produced by Streptomyces ipomoea CECT 3341
      for the biobleaching of pine kraft pulps.
AB  - An endo-beta-mannanase (EC 3.2.1.78) from Streptomyces ipomoea CECT 3341 was
      purified and applied to the biobleaching of pine kraft pulps. The maximum level
      of endo-beta-mannanase activity (0.6 units ml(-1)) was achieved after 4 days of
      growth in a medium containing locust bean gum and yeast extract. Zymograms
      revealed mannanase bands (Man) with high and low electrophoretic mobility on the
      second and seventh days of incubation (Man1, Man3) and three bands of high,
      medium and low mobility from the third to sixth days of growth (Man1, Man2,
      Man3). Although these exhibited different molecular masses, their amino-terminal
      sequences were identical. The action of proteases detected in the culture
      supernatant could be responsible for such events, suggesting that only one endo
      beta-mannanase is produced by S. ipomoea. The purified Man3 exhibited a molecular
      mass of 40 kDa, an isoelectric point of 4.0 and an optimal temperature and pH
      reaction of 55 degrees C and 7.5, respectively. It was strongly inhibited by Ag+,
      Hg2+, Al3+ and Fe3+, and was strongly activated by Mn2+. The ability of the
      purified endo-beta-mannanase to improve the bleachability of pine kraft pulp,
      when applied with alkaline extraction, was demonstrated by an increase in the
      pulp brightness (1.7%, using the International Standards Organisation's test) and
      an absence of variations in the viscosity values. A relationship between the
      increase in pulp brightness and the presence of manganese in the pulps could be
      established.

PMID- 11831475
TI  - Antifungal antibiotics.
AB  - The search for new drugs against fungal infections is a major challenge to
      current research in mycotic diseases. The present article reviews the current
      types of antifungal infections, the current scenario of antifungal antibiotics,
      and the need and approaches to search for newer antifungal antibiotics and
      antifungal drug targets.

PMID- 11831477
TI  - Microencapsulation of Aerococcus viridans with catalase and its application for
      the synthesis of dihydroxyacetone phosphate.
AB  - Dihydroxyacetone phosphate is essential for the synthesis of polyhydroxylated
      compounds used as components or precursors of active pharmaceutical substances,
      such as antibiotics or glycosidase inhibitors. Dihydroxyacetone phosphate was
      produced by enzymatic oxidation of L-alpha-glycerophosphate in the presence of
      glycerophosphate oxidase or Aerococcus viridans coimmobilized with a hydrogen
      peroxide-decomposing enzyme. The microencapsulation of A. viridans with catalase
      in sodium alginate showed a conversion of 98.5%; the conversion percentage
      remained constant in all five runs. Liquid chromatography of the product revealed
      that the product peak corresponded to that of the dihydroxyacetone phosphate
      internal standard. This indicated a high degree of product purity.

PMID- 11831478
TI  - A spontaneous runaway vector for production-scale expression of bovine
      somatotropin from Escherichia coi.
AB  - An Escherichia coli expression vector was constructed for the production-scale
      fermentation of recombinant bovine somatotropin (rBST). Gene expression is
      regulated by a spontaneous increase in copy number at a constant low temperature
      without the need for an external inducer. This vector, designated pURA-4,
      contains the ampicillin resistance gene, the replication origin from pBR322, the
      R1 temperature-inducible runaway replicon, and a gene encoding rBST. Optimized
      rBST expression levels of >35% total cell protein were achieved at a constant 28
      degrees C. Shake-flask analysis of pURA-4 shows that the copy number
      spontaneously increases approximately 6-fold during rBST production.
      Investigation into the mechanism of pURA-4 spontaneous runaway shows that the
      increase in copy number is directed by the pBR322 ori and not by the R1 replicon.
      Although the R1 temperature-inducible replicon does not mediate spontaneous
      runaway, it does have a positive effect on rBST expression. Copy number analysis
      also confirmed the stability of pURA-4 spontaneous runaway from the shake-flask
      scale through the production scale.

PMID- 11831479
TI  - Expression of genes of lipid synthesis and altered lipid composition modulates L
      glutamate efflux of Corynebacterium glutamicum.
AB  - L-Glutamate is made with Corynebacterium glutamicum on a scale of more than 106
      tons/year. Nevertheless, formation of this amino acid is enigmatic and there is
      very limited molecular information available to unravel the apparently complex
      conditions leading to L-glutamate efflux. Here, we report the isolation and
      overexpression of the genes involved in lipid synthesis: acp, fadD 15, cma, cls,
      pgsA2, cdsA, gpsA, and plsC, and the inactivation of cma and cls. In addition,
      the consequences for phospholipid content, temperature sensitivity, as well as
      detergent-independent and detergent-dependent L-glutamate efflux were quantified.
      An in part strong alteration of the phospholipid composition was achieved; for
      instance, overexpression offadD15 encoding an acyl-CoA ligase resulted in an
      increase of phosphatidyl inositol from 12.6 to 30.2%. All strains, except that
      overexpressing acp (acyl carrier protein), exhibited increased temperature
      sensitivity, with the strongest sensitivity present upon cls (cardiolipin
      synthetase) inactivation. As a consequence of the genetically modified lipid
      synthesis, L-glutamate efflux changed quite dramatically; for instance,
      overexpression of plsC (acylglycerolacyl transferase) resulted in a detergent
      triggered increase of L-glutamate accumulation from 92 mM to 108 mM, whereas acp
      overexpression reduced the accumulation to 24 mM. With some of the overexpressed
      genes, substantial L-glutamate excretion even without detergent addition was
      obtained when the fermentation temperature was elevated. These data show that the
      chemical and physical properties of the cytoplasmic membrane are altered and
      suggest that this is a necessary precondition to achieve L-glutamate efflux.

PMID- 11831480
TI  - Identification and characterization of novel cytochrome P450 genes from the white
      rot basidiomycete, Coriolus versicolor.
AB  - Using a reverse-transcription polymerase chain reaction (RT-PCR) technique,
      cytochrome P450 genes were cloned from the lignin-degrading basidiomycete,
      Coriolus versicolor. One possible P450 gene was identified, which consisted of
      1,672 nucleotides and a poly(A) tail and encoded a deduced protein containing 449
      amino acids. The deduced amino acid sequence revealed the presence of the P450
      heme-binding motif, strongly suggesting that this protein belongs to the P450
      superfamily, then designated CYP512A1. The deduced protein showed sequential
      similarity to other known P450s from several micro-organisms, such as Aspergillus
      terreus, Gibberella fujikuroi, and Neurospora crassa, with 30-35% identity. Since
      the identity of the amino id sequence was less than 40% with any other P450s,
      this protein was suggested to be the first member of a new family of cytochrome
      P450. In addition, a differential display RT-PCR analysis showed the expression
      of the other P450 genes, which were up-regulated by the addition of
      dibenzothiophene and 4-methyldibenzothiophene-5-oxide. Using the 5' rapid
      amplification of cDNA ends method, a 520-nucleotide sequence, including the P450
      motif-coding region, was determined for one clone. The deduced protein showed
      high similarity to CYP512A1 but less than 40% identity with P450s from other
      organisms. A chemical stress-responsive expression of P450 is suggested for the
      first time in basidiomycetes.

PMID- 11831481
TI  - One-year follow-up of patients treated for dental fear: effects of cognitive
      therapy, applied relaxation, and nitrous oxide sedation.
AB  - The effects of dental fear treatments were assessed in a 1-year follow-up study.
      Sixty-two patients had finished a controlled study in which they were randomly
      allocated to nitrous oxide sedation (NO), cognitive therapy (CT), or applied
      relaxation (AR). During the trial highly significant reductions in dental fear
      and general distress were observed. One year later a majority (95%) of the
      participants had attended dental treatment in general practice. On the whole,
      continued favorable effects with regard to dental fear and general distress were
      observed. Patients in the applied relaxation group evidenced the largest
      reductions on the dental fear measures. All patients judged the dental fear
      treatment to have been beneficial, and 80% judged the treatment given in the year
      after the dental fear treatment successful. All three treatment groups scored in
      the normative range for general distress both at the end of treatment and at
      follow-up.

PMID- 11831482
TI  - Dental diseases and loss of teeth in a group of Finnish alcoholics: a
      radiological study.
AB  - A total of 85 Finnish alcohol-dependent subjects and 53 controls were studied
      with panoramic radiography. The aim was to study the possible associations
      between prolonged alcohol consumption and dental health. The mean number of
      teeth, caries lesions, endodontic treatments, periapical lesions, marginal bone
      loss, and periodontal infrabony pockets was studied. The subjects met the
      diagnostic criteria of alcohol dependence as set out in DSM-IV and ICD-10. The
      control group comprised social drinking volunteers with an AUDIT score < or =8.
      For the final results the subjects were divided into groups on the basis of sex
      and age. The social backgrounds of the subjects were similar, except for
      employment and smoking. The results show significantly fewer teeth and more
      caries in the alcoholic group. There was a tendency for the alcoholics <45 years
      of age to have more endodontically treated teeth than the controls, but no
      difference in the number of periapical lesions in endodontically treated teeth
      was found. Horizontal bone loss and the presence of calculus were more frequent
      in alcoholic men than in alcoholic women. Significantly more horizontal bone loss
      was observed in the group of alcoholic nonsmokers than in nonalcoholic
      nonsmokers. In the nonsmoking groups alcoholics had significantly more
      periodontal destruction than the nonsmoking controls. We conclude that
      radiological dental health among individuals dependent on alcohol is weakened by
      more caries, more horizontal bone loss, and more numerous vertical infrabony
      pockets than social drinkers.

PMID- 11831483
TI  - Pain mediation by prostaglandin E2 and leukotriene B4 in the human masseter
      muscle.
AB  - The pathophysiology behind chronic pain from masticatory muscles is unclear. Our
      hypothesis was that this pain is of inflammatory origin and associated with
      release of inflammatory mediators. The aim of this study was therefore to
      investigate the presence of prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) in
      the masseter muscle and plasma and their relation to myalgia. Nineteen patients
      with fibromyalgia, 19 with local myalgia of the masseter muscle, and 11 healthy
      individuals were examined with regard to local muscular pain intensity at rest
      and pressure pain threshold. Inclusion criteria were masseter muscle pain for at
      least 3 months and masseter muscle tenderness on digital palpation. Samples were
      obtained from the masseter muscle by microdialysis, and the dialysates and venous
      blood samples were analyzed with regard to PGE2 and LTB4 concentration.
      Intramuscular levels were found in all groups, with significantly higher levels
      of LTB4 in the patients with fibromyalgia, in whom PGE2 was positively correlated
      to muscular pain. In the healthy individuals PGE2 was negatively correlated to
      pressure pain threshold. In both patient groups but not in the healthy
      individuals LTB4 increased during the consecutive samplings. PGE2 and LTB4 were
      detectable in the plasma of all groups. In conclusion, both PGE2 and LTB4 were
      found in the human masseter muscle. LTB4 levels are increased on needle trauma in
      patients with myalgia. PGE2 levels are related to muscular pain in patients with
      fibromyalgia. Masseter muscle pain therefore seems to be partly of peripheral
      inflammatory origin in fibromyalgia.

PMID- 11831484
TI  - Aluminum concentration in deciduous teeth is dependent on tooth type and dental
      status.
AB  - Aluminum (Al) concentration was assessed in deciduous teeth in relation to sex,
      year of birth, tooth type, and the presence of caries and roots. Three hundred
      and twenty-three deciduous teeth from children born during the period 1952 93 in
      a county in southeast Sweden were sampled, and the Al content determined by
      graphite furnace atomic absorption spectrophotometry. The arithmetic mean of the
      Al concentration was 0.58 +/- 0.64 ppm dry weight (mean +/- standard deviation)
      and differed significantly between incisors (1.05 +/- 1.04 ppm) and canines (0.48
      +/- 0.50 ppm) and between incisors and molars (0.53 +/- 0.55 ppm). A significant
      difference was found between teeth with and without caries. No significant
      differences were found between sexes. The Al concentration correlated
      significantly with tooth weight for incisors (r = -0.47) and canines (r = -0.45)
      but not for molars (r = 0.03). No significant change in Al concentration was
      found over time. Caries-free deciduous molars are suggested as the most useful
      teeth for biological monitoring of aluminum.

PMID- 11831485
TI  - Eruption of the central incisor, the intermaxillary suture, and maxillary growth
      in patients with a single median maxillary central incisor.
AB  - The occurrence of a single median maxillary central incisor (SMMCI) is a very
      rare condition and might be a sign of a more severe midline defect, which could
      be a mild degree of holoprosencephaly. Absence of the internasal and partial
      absence of the intermaxillary suture has been observed in a fetus with
      holoprosencephaly. The purpose of this study was to evaluate the intermaxillary
      suture, the eruption pattern of the single central incisor in the SMMCI
      condition, and the growth of the maxilla in a group of patients with SMMCI. A
      similar study was not found in the scientific literature. The material included
      orthopantomographs, dental radiographs, and lateral cephalometric radiographs
      from 11 patients with an SMMCI. The orthopantomographs and dental radiographs
      showed that the intermaxillary suture was abnormal anterior to the incisive
      foramen; however, the SMMCI erupted within the expected time interval.
      Superimposition on stable structures on lateral cephalometric radiographs from
      two untreated patients, in which growth analysis was possible, showed that the
      horizontal and vertical growth of the maxilla was normal. Due to the sutural
      midline defect it is suggested that a transversal growth analysis is included in
      all treatment planning of SMMCI patients.

PMID- 11831486
TI  - Immunohistochemical analysis of epidermal growth factor receptor in cyclosporin A
      induced gingival overgrowth.
AB  - Cyclosporin A (CsA)induced gingival overgrowth represents a tissue of fibrosis
      and epidermal growth factor (EGF) has been shown to induce extracellular matrix
      synthesis by fibroblasts. The purpose of this study was to evaluate the
      expression of EGF-receptor (EGF-r) in frozen sections of CsA-induced overgrown
      gingival tissue using immunohistochemical and semiquantitative techniques.
      Gingival biopsies were obtained from 12 renal transplant patients receiving CsA
      as well as 9 systemically and periodontally healthy individuals.
      Immunohistochemical staining procedures were carried out in frozen sections of
      gingival tissue and the expression of EGF-r was compared between the two study
      groups. The expression of EGF-r was more pronounced in the oral gingival
      epithelium of CsA-induced overgrown gingiva as compared to those of the
      clinically healthy gingival specimens. The reactivity in the inflammatory
      infiltrate and connective tissue cells of both of the study groups was similar.
      In conclusion, the results of the present study may suggest that CsA affects EGF
      r metabolism in gingival keratinocytes resulting in an increased number of cell
      surface receptors, which may eventually play a role in the pathogenesis of
      gingival tissue alterations.

PMID- 11831487
TI  - Equity in access to public dental services: the experience from Norway.
AB  - The aim of this study was to identify possible factors associated with the marked
      geographical variation in supply of public dental services in Norway. We
      identified three sources for this uneven distribution: differences in dental care
      needs, differences in revenue levels between counties, and differences in the
      party composition of the county councils. Analyses were undertaken to ascertain
      whether these factors were related to the variation in the number of man-labor
      years of public dental officers. The analyses were performed on a set of data
      from Norwegian counties for the period 1985-92. There was an association between
      the number of man-labor years of public dental officers and our indicators of
      dental care needs, county revenue, and party composition of the county councils.
      Our findings are encouraging, as they indicate that the county councils seemed to
      respond to the dental care needs of the local population. On the other hand,
      there were inequalities in supply of public dental services that were due to
      differences in revenue between counties. From an equity point of view, this
      inequality is undesirable. The inequality could most likely be reduced by
      decreasing the variation in revenue between counties. Differences in party
      composition of the county councils had only a small effect on the geographical
      variation in the number of man-labor years of public dental officers.

PMID- 11831488
TI  - Effect of denervation on healing after tooth replantation in the ferret.
AB  - Studies have shown that the sensory nerves participate in inflammation and immune
      responses and possess trophic-facilitating wound healing in general. Tooth
      avulsion represents a pulpal and periodontal injury, and the mechanisms involved
      in the healing responses subsequent to replantation of teeth are still unclear.
      The objective of this study was to investigate the healing responses after
      denervation and replantation of teeth. Unilateral denervation was performed in 15
      ferrets by axotomy of the inferior alveolar nerve, 5 days before extraction of
      the first lower premolars. Six weeks later the mandibles were excised and
      processed for histological evaluation. Immunohistochemistry was performed using
      antibodies against the sensory neuropeptides substance P (SP) and calcitonin gene
      related peptide (CGRP), and measurements of root resorption and ankylosis were
      performed in four sections from each replanted tooth. After 6 weeks substantial
      reinnervation was observed in the jaws. Immunoreactivity in the pulp was observed
      in only two replanted teeth on the denervated side, compared with four on the
      innervated side. Total pulp necrosis appeared in 10 replanted teeth on the
      denervated side and in 5 on the innervated, indicating that sensory nerves
      promote survival of the pulp after replantation. SP-immunoreactive (IR) fibers
      were more frequently observed in the resorptive lacunae than CGRP-IR fibers.
      However, resorptive areas lacking IR fibers were frequently found along the root
      surface. Root resorption averaged 0.062 +/- 0.029 mm2 on the innervated side
      compared to 0.016 +/- 0.0043 mm2 on the denervated (P< 0.02). Ankylosis was
      observed in four of the replanted teeth on the innervated side (169.3 +/- 49.7
      microm) and in six on the denervated side (332.56 +/- 193.2 microm) (P = 1). It
      is concluded that the sensory nerves promote root resorption after
      pulpoperiodontal injuries but have less influence on the osteoblastic activity
      expressed by ankylosis.

PMID- 11831489
TI  - Changes in dental conditions during a decade in a middle-aged and older Swedish
      population.
AB  - A questionnaire measuring dental conditions was sent to 2708 individuals aged 55
      79 years in Orebro County, who about 10 years earlier had been randomly selected
      for a similar study. The response rate was 68% (1848 individuals). Of those, 1665
      had participated also in the 1989 study. The objectives were to study changes in
      dental conditions having occurred during a decade and to evaluate whether
      impairment in dental conditions among the participants had resulted in
      prosthodontic treatments. Only small changes in dental conditions were registered
      among those who participated both in 1989 and in 1999. Loss of a single tooth was
      the most frequently reported change. Ten per cent fewer reported that they had
      all teeth remaining in 1999 compared with conditions in 1989. The number of
      subjects wearing removable dentures increased only slightly. Although the
      reported changes in dental conditions were small, there had been a need for
      prosthodontic treatment in many of the subjects. Ten percent of the subjects
      reported that they had received FPD treatment during the past 10 years. To
      conclude, the present study showed that only small changes in dental conditions
      had occurred among the participants during a decade. Nevertheless, a substantial
      increase in the prevalence of prosthodontic appliances, especially of fixed
      restorations, was noted.

PMID- 11831490
TI  - Oral self-care and periodontal health indicators among adults with diabetes in
      Finland.
AB  - We assessed the effects of oral self-care on periodontal health indicators among
      adults with diabetes. The sample consisted of 120 dentate individuals, all of
      whom were regular patients at the Salo Regional Hospital Diabetes Clinic in
      southwest Finland. Clinical periodontal examination included identification of
      visible plaque, the presence of calculus, and use of the Community Periodontal
      Index of Treatment Needs (CPITN). A questionnaire focused on self-treatment, self
      prevention, and self-diagnosis of oral diseases, utilization of dental services,
      and patients' knowledge and attitudes towards oral health. The New Century model
      of oral health promotion was used as a theoretical framework for analysis of
      determinants of oral self-care. Although individuals aged 40 years or older were
      more frequent interdental cleaners, significantly better oral health indicators
      were found among younger patients. Women reported brushing their teeth more
      frequently, and differences in plaque and calculus indices were significantly
      lower than those of men. Self-reported good oral condition was strongly
      associated with frequent dental visits and less plaque and calculus. No missing
      teeth and age less than 40 years were predictors of lower plaque, calculus, and
      CPITN scores. A significant association was found only between frequent dental
      visits and reduced amount of calculus. Self-reported frequency of oral health
      habits among adults with diabetes seemed to have little effect on periodontal
      health indicators. Adults with diabetes should benefit from comprehensive oral
      self-care, and more attention is needed for improving the quality and outcome of
      these habits.

PMID- 11831491
TI  - Required qualifications in the Swedish Public Dental Health Service as indicators
      of organizational ideology.
AB  - The manifestly required qualifications in job advertisements in the Journal of
      the Swedish Dental Association were analyzed as indicators of the organizational
      ideology in the Swedish Public Dental Health Service from the employers'
      viewpoint. All job advertisements that concerned dentists and managers on
      different hierarchical levels in general dentistry from January 1990 to December
      1998 were included (n = 1152). The number of vacancies was 1856. The textual
      material was analyzed by content analysis, permitting quantitative descriptions
      of the text and analysis of the latent characteristics. Words and phrases were
      classified into categories on different levels of abstraction developed from the
      theoretical background and the purpose of the study. Altogether 5705 required
      qualifications were categorized. The inter-coder reliability of the first-level
      categorization resulted in 81% correspondence of the classification, and lambda =
      0.90. Qualifications were more frequently required with higher hierarchical job
      positions, and personality characteristics were more frequent than technical
      competence and knowledge. Qualifications interpreted as related to economic goals
      occurred more frequently than those related to odontological goals. The
      qualification demands reflected the language of human resource management (HRM),
      emphasizing the 'soft' people-centered approach and was interpreted as an 'ideal'
      model of HRM. Dentists were regarded as a profitable organizational asset rather
      than participants in relations with patients. In conclusion, the results indicate
      an organizational ideology primarily of economic character.

PMID- 11831492
TI  - Relationship of depressive symptoms to edentulousness, dental health, and dental
      health behavior.
AB  - We investigated the relationship of edentulousness, dental health, and dental
      health behavior to depressive symptoms in the 55-year-old population of Oulu (a
      medium-sized Finnish town), 780 of whom (78%) participated. The dental
      examination included an assessment of oral health status. Depressive symptoms
      were determined with the Zung Self-Rating Depression Scale (ZSDS). The
      participants were also asked about their dental health behavior, smoking habits,
      health, life satisfaction, and factors related to their work. Depressive symptoms
      were associated with edentulousness among non-smoker men. When further evaluated
      by logistic regression analysis, edentulousness was independently associated with
      depressive symptoms in this subpopulation (odds ratio = 6.4, confidence interval
      = 1.4-29.2) after adjusting for confounding factors. Depressive symptoms were not
      associated with dental caries, periodontal status, or number of teeth. The
      dentate women with high rates of depressive symptoms had a more negative attitude
      towards preserving their natural teeth, used sugary products more frequently,
      reported a longer time since their last dental visit, and tended to have a lower
      percentage of filled tooth surfaces than the non-depressed dentate women. The
      aspect of depression should be borne in mind by dentists when treating edentulous
      patients. On the other hand, certain subgroups of depressed patients might
      benefit from dental implant therapy. Thus, the importance of teamwork between
      clinicians, psychiatrists, and dentists is emphasized.

PMID- 11831493
TI  - Signs and symptoms of temporomandibular disorders in children with different
      types of headache.
AB  - Headache is a common symptom among children and teenagers. Both bruxism and
      muscle and joint tenderness have been found in children with headache. Children
      with migraine headache report more temporomandibular disorder (TMD) symptoms than
      do those with tension-type headache. The aim of the present study was to
      investigate the association of different types of headache with TMD and sex in
      children. Altogether 297 randomly selected schoolchildren aged 13-14 years
      participated in a blind study setting. There were no statistically significant
      differences between the headache groups with regard to TMD signs, although the
      migraine and migraine-type headache groups had the highest percentage of subjects
      with more severe TMD signs. Nor were there any statistical differences between
      sexes or between the headache groups with regard to subjective symptoms of TMD.
      The present results with children differed from earlier results with adults.
      First, no association was found between tension headache and TMD, and, second, no
      sex difference in TMD children was observed at this age.

PMID- 11831494
TI  - Shear strength after ethylenediaminetetraacetic acid conditioning of dentin.
AB  - On the basis of previous studies, it was hypothesized that a chelating agent such
      as ethylenediamine-tetraacetic acid (EDTA) in a saturated aqueous solution (24%)
      can function as a dentin conditioning agent with exposure times comparable to
      that of phosphoric acid without compromising shear bond strength. Thirty caries
      free human third molars, divided equally between two groups, were used. In group
      one, four experimental surfaces were prepared on each tooth, and cylindrical
      copper matrixes with a diameter of 5 mm were attached to the prepared surfaces.
      The experimental surfaces were then treated with a 24% EDTA gel for 30, 60, 120,
      or 240 sec, respectively. Dentin was bonded with All Bond 2, after which a
      flowable composite was added and light-cured. In group two, which served as
      control, two surfaces were prepared on each tooth. One surface was left unetched,
      whereas the other side was treated with 24% EDTA-gel for 30 sec. A shear bond
      strength test was performed at a crosshead speed of 1 mm/min until the composite
      debonded. There was no statistically significant difference (P< 0.89) between
      results of the shear bond strength test for the different EDTA conditioning
      times. The control group showed a significant difference in shear bond strength
      between untreated surfaces and surfaces conditioned for 30 sec with EDTA. Thus,
      the results indicate that the duration of EDTA gel conditioning of dentin
      surfaces need not exceed that of phosphoric acid in clinical practice to obtain
      an acceptable level of bond strength.

PMID- 11831495
TI  - If a US drug abuse epidemic fails to include a major east coast city, can it be
      called an epidemic?

PMID- 11831496
TI  - Status of methamphetamine users 2-5 years after outpatient treatment.
AB  - Increasing numbers of methamphetamine users sought treatment during the decade of
      the 1990s. Little is known about the post treatment status of methamphetamine
      users who enter treatment. The data presented in this paper describe the outcome
      status of a group of a convenience sample of 114 methamphetamine users from a
      total group of 500 methamphetamine users who were treated 2-5 years prior to a
      follow up interview. Since the sample was not randomly selected, no specific
      treatment outcome attribution is possible. Methamphetamine use and other drug use
      of the follow up sample was substantially reduced from pretreatment levels. In
      general, the follow up status of the sample was much improved as compared to
      before treatment. However, headaches and depression were reported at a similar
      rate at follow up as had been reported at treatment admission.

PMID- 11831497
TI  - Patterns of methamphetamine abuse and their consequences.
AB  - The abuse of methamphetamine (METH) continues to increase throughout all age
      groups in different regions of the United States. "Ice," the popularized jargon
      for (+) methamphetamine hydrochloride, is the predominant drug form that is now
      consumed. "Ice" is effectively absorbed after either smoking or snorting and it
      is this rapid influx of drug that produces effects similar to those after
      intravenous administration. The intensity of METH actions in the central and
      peripheral nervous system shows tolerance after chronic administration,
      indicating that neuroadaptations have occurred. Thus, the physiological processes
      and corresponding biochemical mechanisms that regulate neuronal function have
      been changed by METH exposure. These biological alterations contribute to the
      craving and dependence associated with METH abuse and the withdrawal syndrome
      upon abstinence. However, these changes in behavior may also result from METH
      induced neurotoxicity. This article reviews aspects of METH pharmacokinetics and
      related molecular pharmacodynamics that represent METH pharmacology and then
      relates those actions to their potential to produce neurotoxicity in humans.

PMID- 11831498
TI  - A comparison of patterns of methamphetamine and cocaine use.
AB  - Typical use patterns of methamphetamine (MA) users were examined using self
      report measures from 120 MA and 63 cocaine users. Twenty (14 MA and 6 cocaine) of
      the participants also took part in structured interviews designed to provide more
      specific descriptions of their drug use. The typical MA user uses more than 20
      days a month. Use is evenly spaced throughout the day, and although the amount of
      drug used per day is not different, MA users use fewer times per day than do
      cocaine users. Fewer of the cocaine users are continuous users, and they use in
      the evening rather than the daytime. The cocaine pattern of fewer days of use,
      evening use, and more frequent doses per day fits a picture of recreational use,
      whereas the all-day-most-days methamphetamine pattern does not.

PMID- 11831499
TI  - Use ecology and drug use motivations of methamphetamine users admitted to
      substance abuse treatment facilities in Los Angeles: an emerging profile.
AB  - Who are methamphetamine (MA) users and what are the circumstances that surround
      their drug use? This article provides a foundation for future ethnographic
      studies and collaborative clinician-researcher assessments of MA use by
      describing use ecology and drug use motivation for 260 MA users admitted to
      treatment at public Los Angeles County facilities in 1996. Use ecology data
      include MA varieties and street names, first introductions to use, drug use
      histories, access, selling and manufacturing, routes of administration, unwanted
      results of use, and participants' use behavior in the year before the 1996
      treatment. Use motivation data describe clients using MA as a substitute for
      other stimulants; to cope with mental distress; to stay awake; to enhance sexual
      experience; and to lose weight. Qualitative case studies illustrate the findings
      and demonstrate the complex inter-relations of society, culture, psyche and soma
      shaping MA use over time.

PMID- 11831500
TI  - Will the methamphetamine problem go away?
AB  - Methamphetamine use has clearly reached epidemic proportions in large parts of
      the western and midwestern US. Because of the regional specificity of
      methamphetamine use, there is speculation that it may be a temporary problem and
      not a long-term public health problem. Unfortunately there are a number of
      factors that suggest that significant methamphetamine problems may persist or
      even expand. For this reason, it is important that federal law enforcement,
      prevention, research and treatment agencies prepare strategies to address the
      likelihood of this persisting problem. This article reviews the issues concerning
      the future of the methamphetamine problem in the US and provides some
      recommendations for setting priorities to address the problem.

PMID- 11831501
TI  - Cognitive performance of current methamphetamine and cocaine abusers.
AB  - Forty currently using methamphetamine (MA) abusers, 40 currently using cocaine
      (COC) abusers, and 80 comparison participants who did not use psychostimulants
      received a cognitive battery and questionnaires covering medical history and
      stimulant use patterns. Forty comparison participants were matched to the 40 MA
      users on age, education, ethnicity, and gender. The other 40 comparison
      participants were matched to the cocaine users on the same variables. This design
      was chosen because there were significant differences in age and ethnicity
      between COC and MA users that precluded a direct comparison between the groups.
      The COC group was older and predominantly African American compared to the
      predominantly Caucasian MA group. When compared to their matched non-using
      control groups, both MA and COC abusers were impaired on cognitive measures, but
      the type and degree of impairments were somewhat different.

PMID- 11831502
TI  - Cognitive deficits among methamphetamine users with attention deficit
      hyperactivity disorder symptomatology.
AB  - Understanding the association between attention deficit hyperactivity disorder
      (ADHD) and substance abuse, specifically methamphetamine (MA) abuse, is
      challenging, partly because little is known about the specific constellation of
      cognitive impairments produced by MA. The present investigation serves to address
      this relationship by comparing the cognitive performance of MA abusers with ADHD
      symptomatology (n = 28) and MA abusers without ADHD symptomatology (n = 41) on
      tests of attention, memory and general intellectual functioning, executive
      functioning, problem solving, verbal fluency, and abstract thinking. Both MA
      samples had deficiencies in measures of memory and learning function, psychomotor
      speed and abstract thinking when compared to a control group (n = 40). Additional
      deficits were noted on tasks involving executive functioning, attention, and
      general intellectual functioning in MA abusers with ADHD symptomatology. The
      preliminary data suggests that executive function deficits and some of the
      symptoms associated with long-term MA use may be due to the fact that a large
      proportion of MA addicts had ADHD symptomatology as children.

PMID- 11831503
TI  - Patient characteristics, HIV serostatus, and risk behaviors among gay and
      bisexual males seeking treatment for methamphetamine abuse and dependence in Los
      Angeles.
AB  - Methamphetamine, a drug used at alarming rates among gay/bisexual males in the
      West, is often combined with sexual activities, thereby increasing HIV-related
      risks in an already high-risk group. Findings from 68 gay/bisexual men seeking
      treatment for methamphetamine dependence in Hollywood, California were analyzed
      to predict HIV serostatus based on demographic, drug use, or sexual behavior
      variables. Results showed that more HIV-infected participants than non-infected
      men reported medical problems (97.6% versus 46.2%; X2 = 24.7, df = 1, p < .0001),
      histories of genital gonorrhea (59.5% versus 26.9%; X2 = 6.9, df = 1, p < .01),
      use of injection methods (45.2% versus 19.2%; X2 = 4.8, df = 1, p < .03), and
      more sexual partners with unprotected receptive anal intercourse in the 30 days
      prior to intake (5.9 versus 0.7; separate t = 3.5, df = 43.7, p < .001). More non
      infected participants (19.2%) reported suicidal thoughts than HIV-infected men
      (0%; X2 = 4.8, df = 1, p < .03). Discriminant function analysis correctly
      classified 74.6% of cases into serostatus groupings based on presence of suicidal
      thoughts, history of gonorrhea, number of sexual partners with unprotected
      receptive anal intercourse and prior methamphetamine treatment. Findings provide
      information that may prove helpful in tailoring culturally relevant treatment and
      prevention messages.

PMID- 11831504
TI  - Pleiotropic effects in Hereford, Limousin, and Piedmontese F2 crossbred calves of
      genes controlling muscularity including the Piedmontese myostatin allele.
AB  - Objectives were to determine 1) effects on traits measured from birth to
      slaughter in F2 cross calves from sire breeds that differ in potential for lean
      tissue growth but have similar mature BW and 2) the gene action of the mutant
      Piedmontese myostatin allele. Hereford (normal muscling, H), Limousin (moderate
      increase in muscling, L), and Piedmontese (muscular hypertrophy, P) sires (20 to
      25 per breed) were bred at random to crossbred cows to produce F1 calves that
      were inter se-mated within sire breed to produce F2 calves that were grown out,
      finished, and slaughtered. Piedmontese-cross calves were genotyped for the G-A
      transition mutation at the myostatin locus characteristic of P (msP). Genotypes
      were classified on the basis of having zero (P0), one (P1), or two (P2) copies of
      msP (H, n = 227; L, n = 207; P0, n = 40; P1, n = 107; and P2, n = 37). Limousin
      cross F2 calves had heavier birth (but dystocia was not affected) and weaning
      weights, gained faster, had more muscle, less fat, larger pelvic area, and more
      efficient feed conversion than Hereford-cross F2 calves. Normal-muscled
      Piedmontese-cross F2 calves (P0) were similar to Hereford-cross F2 calves except
      that they required less assistance at birth in heifer dams, had less fat, gained
      slower, were less efficient, and had larger pelvic area. Addition of msP alleles
      (P1 and P2) consistently increased muscle through hyperplasia, decreased fat, and
      increased adjusted efficiency, but many of those changes were not linear.
      Residual variances for breed were heterogeneous for most traits related to
      muscularity. This heterogeneity was caused by increased variances for L and P
      and(or) lower variances for H. Accounting for the msP alleles decreased the
      variance for P in most traits, but heterogeneity remained for most traits among
      the five genotypes because L remained high, H was low, and(or) P2 was low. We
      conclude that differences in muscularity affect most traits, and when differences
      in muscularity include the msP allele, there is an incremental, but not equal,
      change in most traits with the addition of each copy of the msP allele.
      Advantages of L could be captured through normal crossbreeding and selection
      schemes but with some caution because of potential problems from increased
      variability. Advantages of P could be best captured through more complex breeding
      and selection programs that would lessen potential negative impacts and through
      marketing systems that do not penalize for very low fat.

PMID- 11831505
TI  - Evaluating the point of separation, during carcass fabrication, between the beef
      wholesale rib and the beef wholesale chuck.
AB  - This study determined whether there is a logical point of value change, related
      to either tenderness or consumer acceptance, at which to separate the beef
      carcass within the rib/chuck region. Rib/chuck rolls (RCR); (n = 30) consisting
      of the ribeye roll and chuck eye roll subprimals (2nd through 12th rib locations)
      were cut into 22 steaks each (two steaks per rib location), and Warner-Bratzler
      shear force and consumer purchase preference were evaluated for steaks at each
      rib location. Steaks from different locations of the RCR were composed of
      differing proportions of several muscles: longissimus muscle (LM), spinalis dorsi
      and multifidus dorsi (SM), and complexus (CO). The LM (4th to 12th rib) contained
      three tenderness regions: 7th through 12th rib, 5th and 6th ribs, and 4th rib
      regions (lowest, intermediate, and highest shear force values, respectively; P <
      0.01). Shear force differed (P < 0.05) among rib locations for the SM (2nd to 9th
      rib), but no logical pattern was evident. The CO (2nd to 7th rib) was more tender
      toward the anterior end (P < 0.05). The region of the RCR represented by the 4th
      through 6th rib locations had steaks with higher weighted-average shear force
      (average shear force of each steak, weighted for surface area of each muscle)
      values than the remainder of the RCR (P < 0.05). Animal-to-animal variation in
      shear force was 36% greater than rib-to-rib variation in shear force; thus,
      statistically significant differences in tenderness among rib locations may be
      undetectable by consumers. Steaks (n = 330) were offered for sale at a retail
      supermarket and case time was monitored on each steak to determine consumer
      purchase preference. Steaks from the 2nd through 4th rib locations required more
      time to sell (P < 0.01) than steaks from the 5th through 12th rib locations. Two
      alternative locations for the rib/chuck separation point could be between the 6th
      and 7th ribs, yielding a ribeye subprimal useful in marketing a "premium quality"
      product, or between the 4th and 5th ribs, which would yield four more 2.5-cm
      ribeye steaks per carcass.

PMID- 11831506
TI  - Effects of dietary conjugated linoleic acid on fatty acid composition, lipid
      oxidation, color, and water-holding capacity of pork loin.
AB  - The effects of dietary conjugated linoleic acid (CLA) on fatty acid composition,
      lipid oxidation, and pork quality were investigated. Pigs (n = 20) were fed a
      diet containing 0, 1, 2.5, or 5% CLA for 4 wk and slaughtered at 105 kg. The
      longissimus thoracis et lumborum muscle was collected at 24 h postmortem. Pork
      loin chops (3 cm thick) were packaged aerobically and stored at 4 degrees C for 7
      d. Samples were analyzed for ultimate pH, intramuscular fat content, fatty acid
      composition, thiobarbituric acid-reactive substances, color (L*, a*, b*), and
      water-holding capacity. Dietary CLA reduced the concentration of linoleic acid
      and increased CLA concentration in intramuscular fat of pork loin (P < 0.05). The
      concentration of CLA in muscle was increased with dietary CLA level and did not
      change during storage. Thiobarbituric acid-reactive substance value of control
      was higher than that of the CLA-fed groups (P < 0.05). Intramuscular fat content
      was increased by dietary CLA, and less purge loss was observed with samples from
      CLA-fed pigs (P < 0.05). Dietary CLA improved the color stability of pork loin
      during cold storage. After 7 d, lightness (L*) and yellowness (b*) of the 5% CLA
      fed group were significantly lower than those of control (P < 0.05). The results
      indicated that the water-holding capacity of pork loin was increased with
      increased intramuscular fat content apparently caused by dietary CLA. Also, the
      data indicated that color stability of pork was improved with inhibition of lipid
      oxidation and changing of fatty acid composition by dietary CLA.

PMID- 11831507
TI  - Prediction of swine carcass composition by total body electrical conductivity
      (TOBEC).
AB  - An experiment was conducted to determine prediction equations that used readings
      for total body electrical conductivity (TOBEC) in the model for estimation of
      total fat-free lean and total fat weight in the pork carcass. Ultrasound
      measurements of live hogs were used to select 32 gilts that represented a range
      in weight, muscling, and fatness. The TOBEC readings were recorded on warm
      carcass sides, chilled carcass sides, and the untrimmed ham from the left carcass
      side. Physical dissection and chemical analyses determined fat-free lean and fat
      weight of the carcass. All of the ham tissues were analyzed separately from the
      remainder of the carcass tissues to incorporate ham measurements for prediction
      of total fat-free lean and total fat weight in the entire carcass. Prediction
      equations were developed using stepwise regression procedures. An equation that
      used a warm carcass TOBEC reading in the model was determined to be the best warm
      TOBEC equation (R2 = 0.91; root mean square error = 0.81). A three-variable
      equation that used chilled carcass TOBEC reading, chilled carcass temperature,
      and carcass length in the model was determined to be the best chilled TOBEC
      equation (R2 = 0.93; root mean square error = 0.73). A four-variable equation
      that included chilled carcass side weight, untrimmed ham TOBEC reading, ham
      temperature, and fat thickness beneath the butt face of the ham in the model was
      determined to be the best equation overall (R2 = 0.95; root mean square error =
      0.65). The TOBEC and the fat-free lean weight of the ham are excellent predictors
      of total carcass fat-free lean weight.

PMID- 11831509
TI  - Increasing tenderness of beef round and sirloin muscles through prerigor skeletal
      separations.
AB  - Crossbred steers (n = 30) were used to explore and compare tenderness
      improvements in beef round and sirloin muscles resulting from various methods of
      prerigor skeletal separations. Animals were slaughtered according to industry
      procedures, and at 60 min postmortem one of six treatments was applied to each
      side: A) control, B) saw pelvis at the sirloin-round junction, C) separate the
      pelvic-femur joint, D) saw femur at mid-point, E) combination of B and C, and F)
      combination of B and D. After 48 h, the following muscles were excised from each
      side: semimembranosus, biceps femoris, semitendinosus, and adductor from the
      round; vastus lateralis and rectus femoris from the knuckle; and gluteus medius,
      biceps femoris and psoas major from the sirloin. Following a 10-d aging period,
      samples were removed from each muscle to determine the effect of treatment on
      sarcomere length and Warner-Bratzler shear force. Most skeletal separation
      treatments resulted in longer sarcomeres than controls for semimembranosus,
      adductor, semitendinosus, and gluteus medius muscles. All skeletal separation
      treatments yielded shorter sarcomeres for the psoas major as compared with
      controls. Warner-Bratzler shear force differed among treatments for rectus
      femoris, semitendinosus, and psoas major. For rectus femoris, treatments C, D, E,
      and F resulted in lower (P < 0.05) shear values than for controls. Treatments B,
      D, and F increased shear force of the semitendinosus relative to controls (P <
      0.05) within muscle. Treatment F resulted in higher shear force values for the PM
      than controls (P < 0.05). Correlations between sarcomere length and shear force
      were found to be low and quite variable among muscles. In general, treatments
      increased sarcomere length of several muscles from the sirloin/round region, but
      had mixed effects on shear force values.

PMID- 11831508
TI  - Effect of pyruvate on the function of stallion spermatozoa stored for up to 48
      hours.
AB  - Stallion spermatozoa maintain high fertilizing capacity if cooled to 5 degrees C
      and inseminated within 24 h. However, if spermatozoa are stored for 48 h,
      fertilizing capacity declines. Therefore, multiple shipments of semen are often
      required to inseminate mares that remain in estrus for days. Therefore,
      experiments were designed to determine if adding antioxidants to stallion
      spermatozoa stored at 5 degrees C for 48 h could maintain motility and
      fertilizing ability. In the first experiment stallion spermatozoa were incubated
      in a skim milk (SM) or a skim milk-egg yolk medium in combination with 10 mM
      pyruvate, 5 mM xanthurenic acid separately or in combination for up to 48 h at 5
      degrees C. Spermatozoa incubated in SM for 48 h exhibited higher percentages of
      motile sperm (57%) than did sperm incubated in skim milk-egg yolk (34%);
      antioxidant treatment had little effect. In the second experiment, spermatozoa
      were incubated in SM containing 0, 1, 2, or 5 mM pyruvate. After 24 h of
      incubation at 5 degrees C, sperm incubated with 1, 2, or 5 mM pyruvate exhibited
      higher percentages of progressively motile spermatozoa (45%) than control
      exhibited (26%; P < 0.05). After 48 h, percentages of progressively motile
      spermatozoa were similar (27, 19, and 30 vs 14, respectively; P > 0.05). However,
      when incubated at 5 degrees C for 48 h and then incubated an additional 4 h at 25
      degrees C, samples containing pyruvate exhibited higher percentages of motile (63
      to 80%) and progressively motile (36 to 42%) sperm than did sperm in SM alone (28
      and 5%, respectively; P < 0.05). The third experiment attempted to determine the
      optimal pyruvate concentration to maintain spermatozoal motility. Spermatozoa
      incubated with 0, 2, 3.5, or 5 mM pyruvate for 48 h at 5 degrees C and then an
      additional 4 h at 25 degrees C, exhibited similar percentages of progressively
      motile cells (31, 35, and 28%, respectively) that were higher than control (11%,
      P < 0.05). The last experiment evaluated the fertilizing potential of cooled
      spermatozoa. Embryos were recovered from 35, 20, and 30% of mares inseminated
      with spermatozoa that had been incubated at 5 degrees C, for 24 h in SM, or for
      48 h in SM or SM + 2 mM pyruvate, respectively (P > 0.05). These studies indicate
      that 2 mM pyruvate in SM was beneficial in maintaining spermatozoal motility in
      48 h-stored sperm and, although not significant, seemed to help maintain the
      fertility of 48 h-cooled spermatozoa.

PMID- 11831510
TI  - Influence of slaughter weight and sex on yield and quality grades of Hanwoo
      (Korean native cattle) carcasses.
AB  - To assess the effects of slaughter weight and sex on APGS (Animal Products
      Grading Service) quality and APGS yield grade of Korean Hanwoo (n = 20,881)
      cattle, data were collected from cow, bull, and steer carcasses during a 1-yr
      period. Factors used to determine quality grade (marbling, meat color, fat color,
      texture, and overall maturity score) and yield grade (cold carcass weight,
      adjusted fat thickness, and longissimus muscle area) by the Korean grading system
      were recorded. Both yield and quality grades were improved (P < 0.01) with
      heavier slaughter weight, but there was no difference in yield grade for Hanwoo
      cattle classes heavier than 551 kg (P > 0.01). Longissimus muscle area, adjusted
      fat thickness, and marbling score increased (P < 0.01) with carcass weight. Bull
      carcasses showed higher yield but lower quality than those of cows or steers (P <
      0.01). The quality grade of steer carcasses was higher (P < 0.01) than that of
      cow carcasses due to higher marbling scores, lower maturity scores, and heavier
      carcass weights. Hanwoo carcasses with larger longissimus muscle areas in
      relation to their carcass weight had lower APGS quality grades. The APGS quality
      grades were different between yield grade A and B carcasses (P < 0.01), but
      quality grade was not improved by increased fat thickness beyond the point of
      yield grade B. Adjusted fat thickness and marbling score showed significant (P <
      0.01) differences among all yield grade classes, and this resulted in increased
      quality grade as yield grade decreased. Adjusted fat thickness showed the
      strongest correlation (r = -0.63) with yield grade, whereas marbling score had
      the strongest correlation (r = 0.81) with quality grade. Results showed a
      negative effect of castration on yield but a positive effect on quality. Also,
      data showed that Hanwoo carcasses with heavier weights had higher quality grades
      than those of lighter weight.

PMID- 11831511
TI  - Effects of high-protein/low-carbohydrate swine diets during the final finishing
      phase on pork muscle quality.
AB  - The aim of this study was to lower the glycogen stores in pork muscle in order to
      improve pork muscle quality by feeding an ultra-high-protein/low-carbohydrate
      (HIPRO) diet. Forty-eight barrows (average live weight = 92 kg) were assigned
      across five treatments and two replications (four or five pigs per treatment by
      replication combination). All barrows were fed a control diet (13.1% CP) until
      their assigned treatment began. A treatment was the number of days the barrows
      were fed the HIPRO diet prior to slaughter (0, 2, 4, 7, or 14 d). The HIPRO diet
      (35.9% CP) was 97% extruded soybeans. Daily feed intake and weekly live weights
      were recorded for all barrows. At-death blood glucose levels were determined.
      Muscle pH, temperature, and electrical impedance were measured in the longissmus
      lumborum and semimembranosus muscles at 45 min, 3 h, and 24 h postmortem.
      Glycolytic potential; Minolta L*a*b* values; visual scores for color, firmness,
      and marbling; water-holding capacity traits (drip loss, purge loss, and cooking
      loss); and Warner-Bratzler shear force values were determined in the longissmus
      thoracis et lumborum. Weight gain per day decreased the longer the pigs were fed
      the HIPRO diet (P < 0.05). Daily feed intake decreased during the 1st wk on the
      HIPRO diet but returned to near-control levels during the 2nd wk, which when
      coupled with the continued decreases in daily gain resulted in substantial
      decreases in feed efficiency during the 2nd wk on the HIPRO diet (P < 0.05).
      Blood glucose levels and glycolytic potentials were not lowered by feeding the
      HIPRO diet (P > 0.05); therefore, no differences in rate of pH decline or
      ultimate pH among dietary treatments were found (P > 0.05). Likewise, there were
      no differences among dietary treatments in any of the measured meat quality
      attributes (P > 0.05). Feeding barrows the HIPRO diet for a time period prior to
      slaughter decreased feed intake, rate of gain, and feed efficiency and was not
      effective at lowering glycolytic potential or improving pork muscle quality.

PMID- 11831512
TI  - Efficacy of partially hydrolyzed corn syrup solids as a replacement for lactose
      in manufactured liquid diets for neonatal pigs.
AB  - Feeding manufactured liquid diets to early-weaned pigs improves growth
      performance and reduces days to market weight compared with pigs receiving
      pelleted dry feed. Few alternative dietary ingredients are utilized in
      manufactured liquid diets other than byproducts of the dairy industry, especially
      for sources of carbohydrates. This experiment was designed to evaluate the
      efficacy of starch from partially hydrolyzed corn syrup solids (CSS), at two
      different levels of hydrolyzation, as a replacement for lactose in manufactured
      liquid diets. Forty-eight pigs were removed from sows at 1 d of age and randomly
      assigned to one of three treatments: 1) control with lactose as the carbohydrate
      source, 2) lactose replaced (gram for gram) with CSS (dextrose equivalent [DE]
      20), and 3) lactose replaced with DE-42. In addition, 10 pigs were randomly
      removed from several litters to provide estimates of initial body composition and
      small intestinal variables. Twenty-four pigs were removed from the study on d 10
      of treatment, and the remaining 24 pigs were removed on d 20 of treatment. Pigs
      averaged 9,845 +/- 191 g at d 20 of treatment regardless of dietary treatment (P
      > 0.20). No differences in ADG, ADFI, or feed efficiency were detected between
      treatment groups from d 0 to 20 (P > 0.19). Whole-body water, protein, lipid, and
      ash accretion rates were unaffected by dietary treatment from d 0 to 10 or from d
      0 to 20 (P > 0.20). The replacement of lactose with CSS did not affect intestinal
      villi height or width, or crypt depth (P > 0.10). Pigs fed lactose tended to have
      greater lactase activity on d 10 than pigs fed CSS (P < 0.07). Also, pigs fed
      lactose tended to have lower oligosaccharidase activity than pigs fed the DE-20
      diet on d 20 (P < 0.07). No other differences in lactase, maltase, or long
      oligosaccharidase specific activity on d 10 or 20 of treatment were detected (P >
      0.12). Plasma urea nitrogen concentrations were unaffected by diet on d 10 and 20
      of treatment. In addition, dry matter digestibility of the diets averaged
      approximately 85.6 +/- 0.8% and was unaffected by dietary treatment or day of
      treatment. These results suggest that partially hydrolyzed CSS can be used as a
      replacement for lactose in manufactured liquid diets for neonatal pigs.

PMID- 11831513
TI  - Long-term effects of boron supplementation on reproductive characteristics and
      bone mechanical properties in gilts.
AB  - An experiment was conducted to determine long-term effects of dietary boron (B)
      on reproductive and bone characteristics in gilts. Weanling gilts (n = 50) were
      allotted to 10 pens based on weaning weight and litter origin. Pens were randomly
      assigned to receive one of two dietary treatments that consisted of a basal diet
      low in B (control) and the basal diet supplemented with 5 mg of B/kg diet as
      sodium borate. Gilts remained on their respective experimental diets throughout
      the nursery phase, growing-finishing phase, sexual maturity, breeding, gestation,
      and lactation. The day of first observed standing estrus was defined as puberty,
      and each pubertal gilt was bred via AI at the second observed standing estrus.
      Eight randomly selected gilts per treatment were slaughtered at d 35 of gestation
      for the assessment of embryonic and reproductive characteristics, bone
      characteristics, and tissue B concentrations. The remaining pregnant gilts
      (control, n = 11; 5 mg supplemental B/kg diet, n = 10) farrowed, and litter
      characteristics at farrowing and weaning were determined. Age at puberty was not
      affected (P = 0.72) by B, and neither were the number of corpora lutea on the
      ovaries (P = 0.44) or the total number of embryos (P = 0.95) at d 35 of
      gestation. Boron supplementation increased (P = 0.05) pig weaning weight and
      tended (P = 0.11) to increase pig birth weight; however, no other litter
      characteristics were affected (P > 0.12) by B. Extrinsic and intrinsic strength
      measures of bone were increased (P < 0.09) by B. Fat-free bone ash percentage and
      bone mineral concentrations were not affected (P > or = 0.19) by dietary B.
      Supplemental B increased (P < or = 0.06) the B concentrations of the muscle,
      liver, and reproductive tissues. Serum osteocalcin concentrations tended (P =
      0.13) to be increased by dietary B, which may be related to increased bone
      turnover in B-supplemented gilts. Results indicate that B may have beneficial
      effects upon reproductive and bone characteristics.

PMID- 11831515
TI  - Evaluation of American Wagyu sires for scrotal circumference by age and body
      weight.
AB  - Thirty-six percent of American Wagyu bulls do not meet the current minimum
      standards set by the Society of Theriogenology for the breeding soundness exam.
      In contrast, only 15% of bulls of domestic breeds do not meet the minimum
      standards. Scrotal circumference measurements of Wagyu are smaller than those of
      other breeds. The objective of this research was to describe scrotal
      circumference of Wagyu bulls as it relates to age and BW. The data set consisted
      of 190 Wagyu bulls housed at two locations. One hundred forty-one bulls
      constituted the first set of data (location 1); scrotal circumference was
      measured one to six times per bull aged between 13 and 70 mo. Ninety-four of the
      bulls underwent semen evaluation for motility and morphology. Forty-nine bulls
      constituted the data set for which scrotal circumference and BW was measured one
      to nine times per bull between 5 and 21 mo of age (location 2). Mean scrotal
      circumference of bulls within each age group was as follows: 12 to 14 mo, 29.8
      0.2 cm (mean +/- SE); 15 to 17 mo, 31.8 +/- 0.2 cm; 18 to 20 mo, 32.9 +/- 0.3 cm;
      21 to 24 mo, 31.8 +/- 0.5 cm; and > 24 mo, 35.5 +/- 0.2 cm. Both age and BW were
      highly correlated to scrotal circumference (r = 0.81 and 0.82, respectively).
      Within each age group, there were a percentage of bulls that did not meet the
      minimum standard for scrotal circumference set by the Society of Theriogenology.
      The percentages were as follows: 12 to 14 mo, 46%; 15 to 17 mo, 25%; 18 to 20 mo,
      33%; 21 to 24 mo, 42%; and > 24 mo, 32%. Morphology and motility were > 50% each
      in 91% of the bulls between ages 12 and 20 mo at location 1. Based on these data,
      it is recommended that Wagyu bulls be evaluated with the breed-specific minimum
      standards for scrotal circumference of 26 cm from 12 to 14 mo, 29 cm from 15 to
      17 mo, and 30 cm from 18 to 20 mo of age.

PMID- 11831514
TI  - Changes in follicular fluid steroids, insulin-like growth factors (IGF) and IGF
      binding protein concentration, and proteolytic activity during equine follicular
      development.
AB  - The objective of the present study was to evaluate changes in equine follicular
      fluid insulin-like growth factor binding protein (IGFBP) proteolytic activity as
      well as steroid, IGF, and IGFBP concentrations during follicular development in
      the mare. Mares (n = 14) were classified as either in the follicular phase (n =
      8) or luteal phase (n = 6). Follicles (n = 92) were categorized as small (6 to 15
      mm; n = 54), medium (16 to 25 mm; n = 23), or large (> 25 mm; n = 15), and
      follicular fluid was collected. Estradiol and androstenedione levels in
      follicular fluid were greater (P < 0.05), and IGFBP-3 concentrations tended to be
      greater (P < 0.10) in large than in small or medium follicles, whereas IGFBP-2, 
      4, and -5 levels were less (P < 0.05) in large than in small or medium follicles.
      Estradiol and androstenedione concentrations were negatively correlated (P <
      0.01) with IGFBP-2, -4, and -5 but not IGFBP-3 concentrations. To evaluate
      proteolysis of IGFBP, follicular fluid was incubated with human 125I-labeled
      IGFBP-2, -3, and -5 and protein separated by 12% SDS-PAGE. Follicular fluid
      caused little or no proteolysis of 125I-lableled IGFBP-2 or -3, and the small
      amount of proteolysis of IGFBP-2 and -3 did not differ (P > 0.10) among follicle
      classes. However, more 125I-labeled IGFBP-5 was cleaved (P < 0.05) by follicular
      fluid from large follicles collected during the follicular phase than large
      follicles during the luteal phase, and small or medium follicles from follicular
      and luteal phase mares indicating that a protease to IGFBP-5 exists in estrogen
      dominant equine follicles. This IGFBP-5 protease was inhibited by
      kallikrein/serine protease and metalloprotease inhibitors. We conclude that the
      tendency of estrogen-dominant follicles of mares to have greater levels of IGFBP
      3 and lesser levels of IGFBP-2 does not appear to be due to differences in
      proteolysis, whereas changes in IGFBP-5 levels are likely due to changes in
      activity of a serine protease or metalloprotease. Changes in IGFBP may alter
      levels of bioavailable IGF that stimulate steroidogenesis and mitogenesis in
      developing mare follicles.

PMID- 11831516
TI  - Technical note: time-resolved fluoro-immunometric assay for intact insulin in
      livestock species.
AB  - Insulin levels in ruminants are often very low and hence are difficult to measure
      with commercially available RIA kits designed for use with human serum or plasma
      samples. Those assays may also have high cross-reactivity with nonintact insulin.
      An assay originally invented for human insulin and based on a pair of monoclonal
      antibodies binding to specific parts of the insulin molecule was further
      developed and validated for use with bovine or porcine plasma or serum. The assay
      is of the sandwich type, with the catching antibody coated to the solid phase of
      microtiter plate wells and with the detecting antibody labeled with europium, and
      measured as time-delayed fluorescence. The assay protocol includes an incubation
      step in which plasma samples of 50 microL are incubated with buffer and detecting
      antibody for 3 h in coated wells, followed by an enhancement step in which the
      fluorescence from the europium label is stabilized before measurement. This gives
      a sensitivity of 3 pmol/L and a possible working range up 16,700 pmol/L. There is
      no cross-reactivity with pro-insulin or IGF-I. Calibrators are prepared in heat
      inactivated serum from the relevant species. Porcine and bovine insulin have
      different calibration curves; porcine insulin is more reactive and has a higher
      background than bovine insulin. Validation results show low CV values, parallel
      dilution of samples, and a recovery ratio close to unity. Comparison with a
      commercial RIA shows good agreement, except at low concentrations, at which the
      RIA determinations are inaccurate. Plasma samples from other domestic species
      (horse, sheep, goat, and mink) have also been assayed, but it is emphasized that
      calibrators should be prepared in heat-inactivated serum from the appropriate
      species, and preferably insulin from that species should be used for calibration.

PMID- 11831517
TI  - Measurement of blood flow through the mammary gland in lactating sows:
      methodological aspects.
AB  - Two replicates of three multiparous crossbred Large White x Landrace lactating
      sows were used to develop a technique for the continuous direct measurement of
      the blood flow through the mammary gland using transit time ultrasound. Four to
      six days after farrowing, an ultrasonic transit time flow probe was implanted
      around the right external pudic artery in order to measure the short-term
      variations of mammary blood flow through this vessel in response to postural
      change (standing vs lying), meal distribution, hand-milking, and weaning. After
      surgery, all sows were fed 3.8 kg/d of a lactation diet and housed either at 20
      or 28 degrees C. The implantation of the ultrasonic blood flow probe was
      successful in all six operated sows. Postmortem examination did not indicate the
      presence of infection, any collateral bypassing the flow probe, or a reduction of
      artery diameter. The right pudic artery mammary blood flow (PMBF) was measured
      for 8.5 h over two periods of three days (d 11 to d 13 and d 18 to d 20 of
      lactation). The PMBF averaged 910 +/- 238 mL/min but was variable within 1 d.
      Compared with the lying position, PMBF was decreased (- 6%, P < 0.05) when sows
      were standing. Between 0 to 15 and 16 to 30 min after oxytocin injection (t = 0)
      and hand-milking, PMBF remained constant (P = 0.05; 801 vs 767 mL/ min) and
      increased (P = 0.02), respectively, in comparison with the mean calculated over
      the preceding 30-min period (982 vs 784 mL/min). The PMBF increased (P < 0.05)
      after meal distribution and reached a peak 65 min later (i.e., 980 mL/min). The
      PMBF decreased regularly after separation of piglets at weaning; at 8 and 16 h
      after weaning, PMBF was 60 and 40% of the value recorded before weaning,
      respectively. Assuming that PMBF drains one-quarter of the whole mammary gland,
      it can be calculated that blood flow through the entire mammary gland averages
      3.6 L/min and that about 470 L of blood are required to produce 1 kg of milk. The
      proposed methodology constitutes a new technique to measure direct mammary blood
      flow and its short-term factors of variation.

PMID- 11831518
TI  - Circulating cortisol, tumor necrosis factor-alpha interleukin-1beta, and
      interferon-gamma in pigs infected with Actinobacillus pleuropneumoniae.
AB  - This study evaluated the time course of systemic cytokine concentrations in an
      acute model of pneumonia in pigs challenged intranasally with Actinobacillus
      pleuropneumoniae. Feed intake and serum cortisol were measured as overt clinical
      and systemic markers of disease onset, respectively, and serum tumor necrosis
      factor-alpha, interleukin-1beta, and interferon-gamma as representative systemic
      inflammatory markers. Crossbred barrows (n = 15), approximately 5 wk of age, were
      used in the study. Pigs were housed in an environmentally controlled facility at
      25 degrees C and under continuous illumination in pens measuring approximately
      1.5 m2. Pigs had free access to water and an unmedicated diet. Approximately 1 wk
      prior to disease challenge, pigs were fitted nonsurgically with venous catheters.
      At challenge, pigs were given 5 x 10(8) CFU Actinobacillus pleuropneumoniae
      intranasally (n = 8) or a similar volume of sterile growth media intranasally
      (Control; n = 7). Feed intake was estimated by the change in feeder weight at 12
      h intervals from -12 to 72 h relative to the time of disease challenge. Blood
      sampling began 12 h prior to challenge and continued until 72 h after challenge.
      Pigs were sampled at -12, -6, and 0 h, then at 90-min intervals until 12-h post
      challenge, continuing at 3-h intervals until 24-h post-challenge, then again at 6
      h intervals until 72 h after challenge. Serum was harvested and frozen until
      assayed for cortisol, tumor necrosis factor-alpha, interleukin-1beta, and
      interferon-gamma. Feed intake was reduced in Actinobacillus pleuropneumoniae pigs
      during the intervals 0 to 12 h (P < 0.001), 24 to 36 h (P < 0.001), 48 to 60 h (P
      <0.05), and 60 to 72 h (P < 0.05). TheActnobacillus pleuropneumoniae-challenged
      pigs had elevated serum cortisol from 180-min to 18-h post-challenge (P < 0.001)
      and also at 36 (P < 0.05), 42 (P < 0.001), and 60 (P < 0.05) h following
      infection. Circulating cytokines were not affected by disease challenge. Thus, in
      this experimental model of pneumonia, weaned pigs demonstrated expected
      behavioral and endocrine characteristics of disease in the absence of significant
      changes in circulating inflammatory cytokines.

PMID- 11831519
TI  - Responses of seasonally anovulatory mares to daily administration of thyrotropin
      releasing hormone and(or) gonadotropin-releasing hormone analog.
AB  - Seventeen seasonally anovulatory light horse mares were treated daily, starting
      January 5 (d 1), for 28 d with GnRH analog (GnRH-A; 50 ng/kg BW) and(or)
      thyrotropin-releasing hormone (TRH; 5 microg/kg BW) in a 2 x 2 factorial
      arrangement of treatments to test the hypothesis that combined treatment may
      stimulate follicular growth and development. Ovaries were examined via
      ultrasonography and jugular blood samples were collected every 3 d. Frequent
      blood samples were collected after treatment injections on d 1, 2, 4, 7, 11, 16,
      and 22; on d 29, all mares received an i.v. mixture of GnRH, TRH, sulpiride, and
      EP51389 (a growth hormone secretagogue) to assess pituitary responsiveness. No
      consistent effects (P > 0.1) of treatment were observed for plasma LH, FSH,
      prolactin, or thyroxine concentrations in samples collected every 3 d. The only
      effect on ovarian follicle numbers was a reduction in number of follicles 11 to
      19 mm in diameter due to TRH treatment (P = 0.029). No mare ovulated during
      treatment. On the days of frequent sampling, mean LH (P = 0.0001) and FSH (P =
      0.001) concentrations were higher in mares receiving GnRH-A and tended to
      increase from d 1 through 7. In contrast, mean prolactin (P = 0.001) and thyroid
      stimulating hormone (P = 0.0001) concentrations were high in mares receiving TRH
      on d 1 but rapidly decreased thereafter. When mares were administered the
      secretagogue mixture on d 29, the LH response was greater (P = 0.0002) in mares
      that had previously received GnRH-A but the FSH response was not affected (P >
      0.1); the prolactin response was greater (P = 0.014) and the TSH response was
      smaller (P = 0.0005) in mares that had previously received TRH. Surprisingly, an
      immediate growth hormone response to EP51389 was absent in all mares. In
      conclusion, daily GnRH-A treatment stimulated plasma LH and FSH concentrations
      immediately after injection; although no long-term elevation in preinjection
      concentrations was achieved, the responses gradually increased over time,
      indicating a stimulation of gonadotropin production and storage. Daily treatment
      with TRH stimulated plasma TSH and prolactin concentrations, but the response
      diminished rapidly and was minimal within a few days, indicating a depletion of
      pituitary stores and little or no stimulation of production. There was no
      beneficial effect of adding TRH treatment to the daily GnRH-A regimen.

PMID- 11831520
TI  - Administration of estradiol-17beta increases anterior pituitary IGF-I and
      relative amounts of serum and anterior pituitary IGF-binding proteins in barrows.
AB  - Two experiments were conducted to determine whether 1) administration of
      estradiol-173 (E2) implants to barrows elevates serum concentrations of E2 to
      levels similar to those of adult boars and subsequently affects the anterior
      pituitary gland IGF system and 2) administration of E2 to barrows increases serum
      concentrations of E2, serum and anterior pituitary concentrations of IGF-I, and
      relative amounts of serum and anterior pituitary IGF-binding proteins (IGFBP), vs
      boars and unimplanted barrows. In Exp. 1, 20 crossbred barrows (150 +/- 6 d, 103
      +/- 8 kg) were administered varying number of E2 implants (0, 2, 3, 4; n =
      5/group) on d 1. Blood samples were collected weekly by jugular venipuncture,
      beginning on d 1. Pigs were killed on d 36 when a blood sample and anterior
      pituitary were collected. Serum concentrations of E2 were increased (P < 0.05) in
      pigs with 2,3, and 4 implants vs 0 implants, but no difference (P > 0.05) was
      detected in serum concentrations of E2 among pigs with 2, 3, and 4 implants.
      Orthogonal contrasts identified that three or four E2 implants were necessary to
      increase serum concentrations of E2 to that similar to boars. Serum and anterior
      pituitary concentrations of IGF-I were increased (P < 0.05) in pigs with 2, 3,
      and 4 implants vs 0 implants. Relative amounts of anterior pituitary IGFBP-2 and 
      5 increased (P < 0.05) in response to administration of E2. In Exp. 2, three
      treatment groups were randomly allotted by litter; boars (n = 11), E2-implanted
      barrows (n = 9), and unimplanted barrows (n = 12). A blood sample was taken from
      all pigs on d 1 and every 14 d thereafter. Implanted pigs received four implants
      on d 1. Pigs were killed on d 91, when a blood sample and anterior pituitary were
      collected. Mean serum concentrations of E2 were greater (P < 0.05) in implanted
      pigs vs boars. Mean serum concentrations of IGF-I (ng/mL) were greater (P < 0.05)
      in boars (238.7 +/- 6.8) than in implanted barrows (170.2 +/- 8.9) and
      unimplanted (150.4 +/- 6.7) pigs and tended to be greater (P = 0.08) in implanted
      vs unimplanted pigs. Mean anterior pituitary concentrations of IGF-I (ng/mg
      tissue) were greater (P < 0.05) in implanted (773.6 +/- 57.0) pigs than boars
      (251.9 +/- 51.6) and unimplanted (185.6 +/- 49.4) pigs. Relative amounts of serum
      IGFBP-2 were greater (P < 0.05) in implanted pigs vs boars. Relative amounts of
      anterior pituitary IGFBP-2 and -5 were greater (P < 0.05) in boars than in
      implanted and unimplanted pigs. These data suggest that E2 may influence
      components of the porcine IGF system in the serum and anterior pituitary. Other
      gonadal factors present in boars may additionally affect the serum and anterior
      pituitary IGF system.

PMID- 11831521
TI  - Intake, digestion, and digestive characteristics of Neotyphodium coenophialum
      infected and uninfected fescue by heifers offered hay diets supplemented with
      Aspergillus oryzae fermentation extract or laidlomycin propionate.
AB  - Tarentaise heifers fitted with a rumen cannula (539 +/- 7.5 and 487 +/- 15.7 kg
      avg initial BW in Exp. 1 and 2, respectively) were used in two Latin square
      metabolism experiments having 2 x 2 factorial treatment arrangements to determine
      the effects of supplementation with Aspergillus oryzae fermentation extract (AO)
      or laidlomycin propionate (LP) on intake, digestion, and digestive
      characteristics of Neotyphodium coenophialum-infected (IF) or uninfected (FF)
      tall fescue (Festuca arundinacea) hay diets consumed ad libitum. Heifers were
      housed in individual stanchions in a metabolism facility with ambient
      temperatures controlled to range between 26.7 and 32.2 degrees C daily. Total
      feces and urine were collected for 5 d following a 21-d dietary adaptation
      period. In situ DM and NDF disappearance and ruminal fermentation characteristics
      were also determined. In Exp. 1, DMI was 24% greater (P < 0.01) by heifers
      offered FF than by those offered IF (6.7 vs 5.4 kg/d). Heifers fed 2 g/d AO
      tended (P = 0.09) to consume 4% more DM than those fed a diet without AO.
      Degradable DM and NDF fractions of IF were greater (P < 0.01) than those of FF,
      but AO supplementation did not affect situ disappearance (P > or = 0.42). In Exp.
      2, DMI was 18.9% greater (P < 0.01) by heifers offered FF than by those offered
      IF (6.6 vs 5.5 kg/d). Heifers fed LP (50 mg/d) consumed 10.6% less (P < 0.05) DM
      than those not fed LP (5.7 vs 6/5 kg/d). Digestibility of NDF tended to be
      greater (P = 0.08) and digestibility of ADF was greater (P < 0.05) from FF than
      from IF. Conversely, apparent N absorption (%) was greater (P < 0.05) from IF
      than from FF. Heifers fed LP had lower (P < 0.05) ADF digestibility than those
      not fed LP. In situ degradable DM and NDF fractions were greater (P < 0.01) from
      IF than from FF. Diets supplemented with LP had higher (P < 0.01) indigestible DM
      and NDF fractions than those without LP. Propionic acid and total VFA
      concentrations were greater (P < 0.05) from heifers offered FF than from those
      offered IF and from heifers fed LP than from those not fed LP. Therefore, it
      appears the major effect of N. coenophialum was a reduction in forage intake and
      total-tract fiber digestibility in certain situations. Response to the feed
      additives was similar whether heifers were offered IF or FF and no evidence was
      apparent that either additive would improve performance substantially by animals
      consuming low-quality fescue hay diets.

PMID- 11831522
TI  - Lactation curves of commercial ewes rearing lambs.
AB  - Three-hour milk production measurements determined by machine milking at 3-d
      intervals throughout a 63-d lactation period were used to describe lactation
      curves for crossbred ewes lambing at 1 and 2 yr of age and rearing single and
      twin lambs. Age of ewe, type of rearing, and day of lactation affected (P < 0.05)
      milk production. Over the 63-d lactation, average daily milk production was 2.56
      and 2.63 kg, respectively, for 1- and 2-yr-old ewes rearing single lambs and 2.73
      and 3.47 kg, respectively, for 1- and 2-yr-old ewes rearing twins. Milk
      production of 2-yr-old ewes rearing twin lambs peaked at 21 d of lactation, and
      that of 1- and 2-yr-old ewes rearing singles peaked between 27 and 30 d of
      lactation. The largest differences in the lactation curves among age and rearing
      ewe classes were found in early lactation. These differences were reduced by
      midlactation, and by late lactation, milk production for all ewes was similar.
      Diurnal variation in milk production by ewes was evaluated in an 8 x 8 Latin
      square design. Diurnal variation in milk yield measurements of eight mature ewes,
      each bearing and rearing twin lambs, was similar between d 21 and 24 of
      lactation. Time of milk production measurements within a day did not affect yield
      determinations. Extrapolation from 3-h production estimates to daily milk
      production is valid in determining a ewe's milk contribution in support of lamb
      growth.

PMID- 11831523
TI  - Kinetics of ruminal degradation of wheat and potato starches in total mixed
      rations.
AB  - Wheat and potato are rich in starch but their starches differ in their rate of
      ruminal degradation. Kinetics of in sacco disappearance and profiles of ruminal
      fermentation were studied for these two concentrates in total mixed rations based
      on grass silage or corn silage. Wheat starch was more rapidly (34%/h) degraded by
      rumen microorganisms than potato starch (5%/h). The differences in starch
      degradation in sacco were found again in the VFA concentrations, mainly in grass
      silage-based diets. Overall ruminal pH, total VFA concentration, and proportions
      of acetate, propionate, and butyrate are more variable for wheat during the
      kinetic (amplitude and quickness) than for potato in grass silage-based diets. In
      these diets, risks of acidosis were more elevated with wheat than with potato but
      the VFA concentrations were also higher. These differences of fermentation
      profile were so reduced in corn silage-based diets that, in this case, wheat can
      be substituted by potato without any effect on digestion and no risk of acidosis.

PMID- 11831524
TI  - Effect of corn processing on degradable intake protein requirement of finishing
      cattle.
AB  - Three finishing trials were conducted to determine effect of corn processing on
      degradable intake protein requirement (DIP) of feedlot cattle. In Trial 1, 252
      steers were fed 90% concentrate, high-moisture corn-based diets that contained 0,
      0.4, 0.8, or 1.2% urea (DM basis) to provide dietary DIP values of 7.0, 8.2, 9.3,
      and 10.5% of DM, respectively. Nonlinear analysis predicted maximal feed
      efficiency at 10.2% dietary DIP (95% confidence interval was 9.9 to 13.3%). In
      Trial 2, 264 steers were fed 90% concentrate, steam-flaked corn-based diets that
      contained 0, 0.4, 0.8, 1.2, 1.6, or 2.0% urea (DM basis) to provide dietary DIP
      values of 4.7, 5.8, 7.0, 8.2, 9.3, and 10.5% of DM, respectively. Nonlinear
      analysis predicted maximal feed efficiency at 7.1% dietary DIP (95% confidence
      interval was 7.0 to 7.2%). In Trial 3, 90 individually-fed steers were fed 90%
      concentrate, dry-rolled, high-moisture, or steam-flaked corn-based diets. Urea
      was factored across diets at 0, 0.5, 1.0, or 2.0% of DM to provide dietary DIP
      values of 4.8. 6.3, 7.8, 9.2, and 10.7% for dry-rolled, 6.7,8.1,9.6, 11.1, and
      12.5% for high-moisture, and 4.7, 6.1, 7.6, 9.0, and 10.5% for steam-flaked corn
      based diets, respectively. For the dry-rolled corn-based diet, nonlinear analysis
      could not predict a requirement because feed efficiency was not improved beyond
      the first increment of dietary DIP, suggesting that the DIP requirement was met
      at 6.3% of DM. For the high-moisture corn-based diet, nonlinear analysis
      predicted maximal feed efficiency at 10.0% dietary DIP (95% confidence interval
      was 9.2 to 11.3%). For the steam-flaked corn based diet, nonlinear analysis
      predicted maximal feed efficiency at 9.5% dietary DIP (95% confidence interval
      was 9.2 to 9.5%). Our estimate of the DIP requirement for dry-rolled corn-based
      diets (6.3%) agrees well with past research and predicted values. Our estimate of
      the DIP requirement for high-moisture corn-based diets (10.1%) was very
      consistent between trials and higher than predicted. Our estimates of the DIP
      requirement for steam-flaked corn-based diets varied from 7.1 to 9.5%, with an
      average of 8.3% of dietary DM.

PMID- 11831525
TI  - Effects of residual and reapplied biosolids on performance and mineral status of
      grazing beef steers.
AB  - An experiment was designed to assess the mineral status of 60 Angus yearling beef
      steers grazing bahiagrass pastures fertilized with large amounts of biosolids
      from three sources: Baltimore, MD; Tampa, FL; and Largo, FL. Biosolids were
      classified as exceptional quality and thus had no regulatory restrictions on
      loading rate. They differed primarily in concentration of Mo (12 to 56 mg/kg of
      DM). Residual treatments (biosolids applied only the previous year) for Baltimore
      biosolids were applied at 22.4 and 44.8 t/ha, and Tampa biosolids were either
      16.8 or 33.6 t/ ha. The reapplied treatments (applied in consecutive years) for
      both Baltimore and Tampa sludges were applied at 22.4, 44.8, 16.8 , and 33.6
      t/ha, respectively. The two Largo biosolids treatments were either 56 or 112 t/ha
      and were applied only in the 2nd yr. Liver biopsies and blood samples were
      collected on d 1, 95, and 180. Liver and plasma were analyzed for minerals and
      blood was analyzed for hemoglobin, hematocrit, and superoxide dismutase of
      polymorphonuclear neutrophils. Experimental animals were generally adequate in
      macromineral status and Co, Fe, and Mn throughout the experiment. Copper
      deficiency was evident based on the clinical signs of hair coat discoloration,
      very low plasma Cu at d 95, and the continuous decline in liver Cu over 180 d. A
      sharp decline in plasma Cu was observed for all treatments from d 1 to 95, after
      which Cu concentrations rebounded to normal concentrations (> 0.65 microg/mL) by
      d 180. Liver Mo was well below concentrations indicating toxicity (> 5.0 mg/kg).
      The steep decline in liver Cu over the first 95 d reflects the dietary Cu
      deficiency and the possibility of high forage S (0.26 to 0.52%) interfering with
      Cu metabolism. Biosolids application to bahiagrass pastures was not detrimental
      to mineral status except for declining Cu stores; however, the controls likewise
      declined, but to a lesser degree.

PMID- 11831526
TI  - Volatile fatty acid metabolism by epithelial cells isolated from different areas
      of the ewe rumen.
AB  - Cells were harvested from four rumen locations in four 2- to 3-yr-old ewes fed
      fescue hay to determine whether cell origin has an effect on cellular VFA
      metabolism. Tissue (approximately 150 cm2) was excised from the anterior cranial
      pillar, ventral sac floor, caudal pillar surface, and dorsal sac ceiling. Cells
      were isolated using serial tryptic digestion. One milliliter of isolate was
      incubated for 2 h in 6 mL of medium containing 25 mM propionate and 10 mM
      butyrate. Incubations were terminated at 0, 30, 60, 90, and 120 min and analyzed
      for beta-hydroxybutyrate, acetoacetate, lactate, and pyruvate. Cell yield was 22,
      22, 24, and 14 (+/- 6) x 106 cells/mL, and viability was 92, 92, 94, and 87% for
      anterior cranial pillar, ventral sac floor, caudal pillar surface, and dorsal sac
      ceiling, respectively. All metabolite concentrations and ratios of redox pairs
      increased throughout the incubations, indicating continuous cellular activity.
      Final 2-h concentrations (nmol/10(6) cells) were 123, 113, 163, and 158 (+/- 35)
      for beta-hydroxybutyrate; 38, 42, 24, and 45 (+/- 10) for acetoacetate; 25.3,
      20.6, 10.1, and 20.4 (+/- 5.6) for lactate; and 2.54, 0.98, 1.06, and 1.31 (+/-
      0.61) for pyruvate in the anterior cranial pillar, ventral sac floor, caudal
      pillar surface and dorsal sac ceiling incubations, respectively. Origin of rumen
      tissue had no significant effect on metabolite production, indicating that
      cellular location is not a critical factor that affects rate of rumen epithelial
      cell VFA metabolism under these specific in vitro conditions.

PMID- 11831527
TI  - Early-weaning and postweaning nutritional management affect feedlot performance,
      carcass merit, and the relationship of 12th-rib fat, marbling score, and feed
      efficiency among Angus and Wagyu heifers.
AB  - Twelve 3/4 Angus (Angus) and 12 Wagyu-cross (1/2 Wagyu x 1/2 Angus) (Wagyu)
      heifers were weaned at 180 d of age and grazed on endophyte-infected tall fescue
      for 16 mo before entering the feedlot as 2-yr-olds. Twelve 3/4 Angus heifer
      calves and 12 Wagyu-cross heifer calves from the following year's calf crop were
      weaned at 142 +/- 4.1 d of age, immediately adjusted to an 80% concentrate diet,
      and finished as calves. All heifers were fed a common finishing diet until an
      estimated 50% of their respective group would grade USDA low Prime or better
      based on ultrasound predictions. Ultrasound measurements of s.c. and i.m. fat
      depots were recorded at 60-d intervals throughout the finishing period. Heifers
      finished as calves had higher (P = 0.02) marbling scores at any given fat
      thickness and gained more efficiently (P < or = 0.01) at any given marbling score
      than heifers finished as 2-yr-olds. Gain:feed decreased quadratically (P < or =
      0.05) as 12th-rib fat thickness increased for Angus and Wagyu heifers. Gain:feed
      decreased linearly (P < or = 0.01) for Wagyu calves and quadratically (P < or =
      0.01) for Angus calves as 12th-rib fat thickness increased. However, these
      differences in slope were not different (P = 0.34) as a result of breed among
      heifers finished as calves. Marbling score increased linearly (P < or = 0.01) as
      12th-rib fat thickness increased for Angus and Wagyu heifers finished as 2-yrolds
      or as calves. However, Wagyu heifers, regardless of age at feedlot entry, had a
      higher marbling score (P < or = 0.05) at any given 12th-rib fat thickness than
      Angus heifers. Finishing early-weaned heifers as calves as opposed to 2-yr-olds
      results in i.m. fat deposition during a period of more efficient growth.
      Additionally, including Wagyu genetics into the breeding of early-weaned heifers
      finished as calves or as 2-yr-olds results in higher marbling scores at any 12th
      rib fat thickness.

PMID- 11831528
TI  - Dietary medium- or long-chain triglycerides improve body condition of lean
      genotype sows and increase suckling pig growth.
AB  - In a field trial conducted on a commercial swine farm, lean-genotype sows (n =
      485) were fed diets containing 0 or 10% supplemental fat as either medium-chain
      triglyceride or choice white grease from d 90 of gestation until weaning (15.5
      d). Effects on standard sow and litter production traits were examined together
      with assessment of sow body condition using live ultrasound. Daily feed intake
      during lactation was 10% higher in sows consuming diets without added fat (7.2 vs
      6.5 kg; P < 0.01); however, lactation ME (23.9 Mcal/d) and digestible lysine (54
      g/d) intakes were unaffected (P > 0.10). Sows supplemented with fat were 4 kg
      heavier on d 109 of gestation (220 vs 224 kg; P < or = 0.01), 1 d after farrowing
      (210 vs 214 kg; P < or = 0.01), and at weaning (210 vs 214 kg; P < or = 0.01).
      Expressed as overall gain, this amounted to a 23% increase (0.66 vs 0.86 kg/d; P
      < or = 0.01) and was accompanied by a 49% increase in backfat (0.82 vs 1.68 mm; P
      < or = 0.03) from d 90 to farrowing. Changes in sow weight (-0.01 kg/d) and
      backfat (+4.2 mm) over lactation were minimal and were not affected by fat
      supplementation (P > or = 0.10). Longissimus muscle area at weaning was slightly
      greater (44.96 vs 46.2 cm2) in sows consuming fat than in control sows (P < or =
      0.05), but changes in longissimus muscle area were not significant from d 90 to
      weaning (P > or = 0.10). Gestation length, pigs born alive, average birth weight,
      survival (d 3 to weaning), and days to estrus were not affected by diet (P >
      0.10). However, supplemental fat increased pig ADG (192 vs 203 g/d; P < 0.01) and
      average pig weaning weight (4.3 vs 4.5 kg) at 15.5 d (P < or = 0.02). No
      differences between the two fat sources were detected. This large-scale study
      demonstrated that supplemental fat during gestation and lactation effectively
      improved sow condition and improved suckling pig performance without affecting
      energy intake during lactation, implying improved efficiency of sow energy
      utilization.

PMID- 11831529
TI  - Nuclear, cytoplasmic, and environmental effects on growth, fat, and muscle traits
      in suffolk lambs from a sire referencing scheme.
AB  - Maternal effects are an important source of variation in early growth and body
      traits in sheep but are often excluded from genetic analyses. Maternal additive
      genetic, maternal environmental, and cytoplasmic effects were investigated in a
      large Suffolk breeding scheme using a range of models involving different
      combinations of these effects with the direct additive genetic effect. Weights at
      8 wk of age and at scanning (mean age 146 d) and ultrasonically measured muscle
      and fat depth were analyzed using an animal model on 55,683 (8-wk weight) and
      28,947 (scanning traits) lamb records. Simple additive models always
      overestimated the heritability of all traits when compared to more complex
      models. The successive inclusion of maternal environmental, maternal genetic, and
      the covariance between direct and maternal additive effects in the model
      significantly improved the fit for almost all models and all traits, as indicated
      by a likelihood ratio test. Under the full model, the heritability of both weight
      traits was low (0.14 and 0.20 for 8-wk and scanning weight, respectively). The
      maternal additive and maternal environmental effects, as a proportion of the
      phenotypic variance, were similar (0.10 and 0.08 for 8-wk weight and 0.07 and
      0.06 for scanning weight). The two scanning traits had higher heritabilities
      (0.29 and 0.27 for muscle depth and fat depth, respectively) with low levels of
      maternal genetic and maternal environmental variance. No evidence was found of a
      cytoplasmic effect on any of the traits studied under the full model. Breeding
      schemes for early growth and body traits in sheep should account for maternal
      effects in their genetic evaluations in order to improve their accuracy. The
      exact model to use will depend on the trait and individual circumstances of the
      scheme.

PMID- 11831530
TI  - The effects of cognitive behavioral intervention on the attitude and behavior of
      stockpersons and the behavior and productivity of commercial dairy cows.
AB  - Two experiments, one involving 29 commercial farms and the other involving 94
      commercial farms, were conducted to examine the effects of a training program
      targeting a number of attitudinal and behavioral variables in stockpeople. These
      stockperson variables had been previously shown to be related to fear of humans
      and productivity of commercial cows. In both experiments, two treatments were
      imposed: an Intervention treatment, consisting of a cognitive-behavioral
      intervention procedure designed to improve the attitude and behavior of
      stockpeople toward cows, and a Control treatment, in which no intervention was
      attempted. In Exp. 1, an analysis of covariance, using previous lactation
      variables as the covariate, revealed effects of the Intervention treatment on the
      attitude and behavior of the stockpeople and the behavior of cows. Stockpeople at
      Intervention farms showed more (P < 0.01) positive beliefs about handling cows
      and used a lower (P < 0.05) number and percentage of negative tactile
      interactions in handling cows than stockpeople at the Control farms. Cows at the
      Intervention farms showed a shorter (P < 0.05) flight distance to humans,
      indicating a lower level of fear of humans by these cows. However, 36% of the
      Intervention farms failed to show a reduction in average flight distance over the
      two lactations. Although there was no significant treatment effect on milk yield,
      the Intervention farms in which fear levels declined following the intervention
      had a higher (P < 0.05) milk yield than the other farms. In Exp. 2, a significant
      (P < 0.05) increase was found in the milk yield of cows following the
      Intervention treatment. Similar treatment effects were observed on both milk
      protein and milk fat. These results indicate that cognitive-behavioral
      interventions that successfully target the key attitudes and behavior of
      stockpeople that regulate the cow's fear of humans offer the industry good
      opportunities to improve the productivity of cows.

PMID- 11831531
TI  - Conditioning taste aversions to locoweed (Oxytropis sericea) in horses.
AB  - Locoweed (Oxytropis sericea) is a serious poisoning problem for horses grazing on
      infested rangelands in the western United States. Our objectives were to
      determine 1) whether lithium chloride or apomorphine would condition aversions to
      palatable foods, and at what doses, and 2) whether horses could be averted to
      fresh locoweed in a pen and grazing situation. Apomorphine was not an acceptable
      aversive agent because at the dose required to condition an aversion (> or = 0.17
      mg/kg BW), apomorphine induced unacceptable behavioral effects. Lithium chloride
      given via stomach tube at 190 mg/kg BW conditioned strong and persistent
      aversions to palatable feeds with minor signs of distress. Pen and grazing tests
      were conducted in Colorado to determine if horses could be averted to fresh
      locoweed. Pen tests indicated that most horses (5/6) were completely averted from
      locoweed. Treated horses ate 34 g of fresh locoweed compared to 135 g for
      controls (P < 0.01) during three pen tests when offered 150 g per test. One horse
      (T) in the treatment group ate locoweed each time it was offered in the pen, but
      ate no locoweed while grazing. In the grazing trial, control horses averaged 8.6%
      of bites of locoweed (P < 0.01) during the grazing portion of the study, whereas
      treated horses averaged <0.5%. One treated horse (S) accounted for all
      consumption; he consumed 15% of his bites as locoweed in a grazing bout on d 2 of
      the field study. Thereafter, he was dosed a second time with lithium chloride and
      ate no locoweed in the subsequent 5 d. Three of six horses required two pairings
      of lithium chloride with fresh locoweed to condition a complete aversion. The
      results of this study indicate that horses can be averted from locoweed using
      lithium chloride as an aversive agent, and this may provide a management tool to
      reduce the risk of intoxication for horses grazing locoweed-infested rangeland.

PMID- 11831532
TI  - Effects of restricted feeding, low-energy diet, and implantation of trenbolone
      acetate plus estradiol on growth, carcass traits, and circulating concentrations
      of insulin-like growth factor (IGF)-I and IGF-binding protein-3 in finishing
      barrows.
AB  - Effects of restricted feeding (80% ad libitum), feeding a low-energy diet
      containing 84% DE (2.95 Mcal/kg) of the control diet, and implantation of Revalor
      H (140 mg trenbolone acetate plus 14 mg estradiol-17beta) on growth, carcass
      traits, and serum concentrations of insulin-like growth factor (IGF)-I and
      IGFbinding protein-3 (IGFBP-3) were studied in crossbred finishing barrows
      beginning from 59 +/- 0.9 kg of body weight. Blood samples were taken every 3 wk
      and the animals were slaughtered at approximately 105 kg body weight. Restricted
      feeding caused a decrease (P < 0.01) in ADG; feeding the low-energy diet was
      effective in reducing backfat thickness but decreased gain:feed; the implantation
      caused a decrease in ADG, feed intake, and backfat thickness and increased
      gain:feed. Overall pork quality based on pH, drip loss, and the lightness in
      color of longissimus muscle was not affected by any of the treatments. Serum IGF
      I concentration increased following the implantation but did not change (P >
      0.05) due to other treatments. Immunoreactive IGFBP-3 concentration was not
      changed by any of the treatments. Overall ADG was positively correlated with
      early-stage (d 21) IGF-I and IGFBP-3 concentrations only in unimplanted barrows,
      whereas backfat thickness was negatively correlated with d-42 IGF-I concentration
      in all but unimplanted barrows with ad libitum intake. A strong positive
      correlation (P < 0.01) between IGF-I and IGFBP-3 concentrations was apparent with
      increasing age of the animals. Results suggest that growth rate and backfat
      thickness are decreased by a moderate restriction of feed or energy intake with
      no accompanying changes in circulating IGF-I and IGFBP-3 concentrations and that
      the beneficial effect of Revalor H implantation on feed efficiency may be
      mediated, in part, by IGF-I. Moreover, both IGF-I and IGFBP-3 concentrations may
      be useful as growth indices in pigs.

PMID- 11831533
TI  - The influence of level of feeding on growth and serum insulin-like growth factor
      I and insulin-like growth factor-binding proteins in growing beef cattle
      supplemented with somatotropin.
AB  - The objective of this study was to determine the effects of level of feeding on
      growth, feed efficiency (gain:feed; G:F), body composition (BC), and serum
      concentrations of somatotropin (ST), IGF-I, and IGF-binding proteins (BP) in
      growing beef cattle supplemented with bovine (b) ST. In each of two consecutive
      years, 40 growing beef cattle were blocked by weight (average BW: yr 1 = 316 kg,
      yr 2 = 305 kg) and used in a 2 x 2 factorial arrangement with main effects of bST
      (0 or 33 microg x kg BW(-1) x d(-1)) and level of feed intake (ad libitum [AL] or
      0.75 AL). Relative to uninjected cattle, treatment with bST increased ADG 9.6%
      (1.14 vs 1.25 kg/d; P < 0.05) and increased G:F 8.1% (12.3 vs 13.3 gain [g]:feed
      [kg]; P < 0.05), whereas ADG in AL animals was 39% greater than that in 0.75 AL
      animals (1.39 vs 1.00 kg/d; P < 0.05). There was a tendency (P = 0.10) for a bST
      x level of feeding interaction, such that the increase in ADG with bST was
      greater in AL cattle than in 0.75 AL cattle (10.6 vs 7.8%; P = 0.10). Serum
      concentrations of ST were greater in 0.75 AL cattle than in AL cattle (13.0 vs
      8.6 ng/mL; P < 0.05) and in bST-treated cattle than in uninjected cattle (16.3 vs
      5.2 ng/mL; P < 0.05). Due to a bST x level of feeding interaction (P < 0.01), the
      magnitude of the increase in serum ST to exogenous bST was greater (P < 0.01) in
      0.75 AL cattle than in AL cattle. Relative to uninjected cattle, treatment with
      bST increased (P < 0.05) serum concentrations of IGF-I and IGFBP-3 and reduced (P
      < 0.05) concentrations of IGFBP-2. Similarly, AL cattle had greater (P < 0.05)
      serum concentrations of IGF-I and IGFBP-3 and reduced (P < 0.05) IGFBP-2 compared
      with 0.75 AL cattle. In summary, treatment with bST increased growth rate and G:F
      and stimulated serum IGF-I and IGFBP-3 while reducing IGFBP-2. Feeding at 0.75 ad
      libitum intake reduced the magnitude of response for each of these variables.
      Thus, limit-feeding may reduce the effect of exogenous bST on growth rate by
      blunting bST-induced increases in IGF-I and IGFBP-3 and bST-induced decreases in
      IGFBP-2.

PMID- 11831534
TI  - Clinical pharmacology: drugs as a benefit and/or risk in sudden unexpected death
      in epilepsy?
AB  - Death may be the consequence of natural or unnatural causes, such as accidents,
      homicide, and suicide, which have no relationship to the disease of epilepsy.
      Direct causes of death include status epilepticus, and indirect causes may be
      head trauma or drowning subsequent to a seizure. When death occurs suddenly and
      without explanation, the term sudden unexpected unexplained death is used.
      Unexplained is a term that clinicians and research scientists are working to
      clarify. Numerous preclinical animal studies have been conducted as models for
      sudden death and have led to clinical studies in persons with epilepsy. These
      studies show that sympathetic nerve stimulation, ouabain, or coronary occlusion
      increased temporal dispersion of recovery of ventricular excitability and led to
      an underlying electrical instability that predisposed the ventricularmyocardium
      to arrhythmia. Cardiac arrhythmias in an animal model for ouabain-induced
      toxicity were associated with neural autonomic dysfunction. Neural discharges
      were characterized by increases, decreases, or no change in the discharge of
      postganglionic cardiac sympathetic nerves monitored simultaneously, predisposing
      to cardiac arrhythmia. Stimulation of the sympathetic ventrolateral cardiac nerve
      produced a shift in the origin of the pacemaker and tachyarrhythmias because the
      nerve is not uniformly distributed to the various regions of the heart but is
      localized to the atrioventricular junctional and ventricular regions. Such
      nonuniform distribution of sympathetic nerves would also contribute to initiation
      of arrhythmia as a nonuniform neural discharge occurred. Studies examining the
      physiology and pharmacology of this finding in multiple animal models found that
      subconvulsant, interictal discharge was associated with autonomic cardiac neural
      non-uniform discharge and cardiac arrhythmias. As a result of further
      investigations, Lathers and Schraeder edited a book in 1990 that summarized the
      clinical problem of sudden unexpected death and epilepsy (SUDEP). The
      contributors concluded that there was a paucity of clinical data addressing the
      mechanism of death. Regulatory response resulting from the consequent increased
      awareness of SUDEP occurred in 1993, when the FDA focused attention of
      practitioners and pharmaceutical manufacturers on the question of whether use of
      anticonvulsant drugs contributes to or prevents sudden unexpected death in
      epileptic persons. The FDA-convened panel of scientists considered the prevalence
      of sudden unexpected death in patients involved in studies associated with
      developing new anticonvulsant drugs and reviewed data on the risk of sudden
      unexpected death in patients taking lamotrigine. The risk of SUDEP was no
      different from thatfound in the young epilepsy population in general. Estimated
      SUDEP rates in patients receiving the new anticonvulsant drugs lamotrigine,
      gabapentin, topiramate, tigabine, and zonisamide were found to be similar to
      those in patients receiving standard anticonvulsant drugs, suggesting that SUDEP
      rates reflect population rates and not a specific drug effect. The FDA required
      warning labels on the risk of SUDEP in association with the use of each of the
      above-mentioned drugs. Another effect of bringing SUDEP to the attention of
      epilepsy researchers has been the expansion of basic science and the development
      of epidemiological and clinical studies directed at this phenomenon. Results from
      some of these studies are discussed in this article.

PMID- 11831535
TI  - Oral hormone replacement therapy: factors that influence the estradiol
      concentrations achieved in a multiracial study population.
AB  - The assumption that estradiol (E2) concentrations are reliably increased to
      therapeutic levels in postmenopausal women receiving hormone replacement therapy
      (HRT) has not been explicitly tested. Nor have factors that may modulate the E2
      levels achieved been evaluated. The author examined E2 concentrations in a
      multiracial study population of 309 postmenopausal women treated with oral HRT
      and observed that 51.1% had achieved estradiol levels of at least 45 pg/ml
      (achievers). The odds of being an achiever were significantly elevated among non
      Caucasian women by a HRT dose greater than 0.625 mg, current moderate drinking,
      and increasing duration of HRT use. The odds were significantly decreased by
      having a high school education or less and increasing time since last HRT dose.
      White postmenopausal women had significantly reduced odds of being an achiever,
      and both a dose of less than 0.625 mg and a dose equal to 0.625 mg significantly
      reduced the odds of being an achiever. Increasing body mass index and menopause
      duration were both associated with lower odds. This report demonstrates not only
      that women treated with HRTdo not all achieve therapeutic levels of estradiol but
      also that factors can be identified that modulate the E2 concentration achieved
      in response to HRT administration.

PMID- 11831536
TI  - Increased sensitivity to warfarin in elderly Hispanics.
AB  - It has been suggested that aging enhances the pharmacologic effect of warfarin,
      but there is little information about the effects of warfarin in aging minority
      populations. The authors examine the response of an aging Hispanic population to
      warfarin. Charts in their anticoagulation clinic were retrospectively examined
      for the following information: age, sex, weight, duration of anticoagulant
      therapy, number of medical problems, number of medications, number of minor or
      major bleeding episodes, prothrombin time, warfarin dose, and international
      normalized ratio (INR). The dose-adjusted prothrombin time ratio (PTR) and dose
      adjusted INR were calculated by dividing the PTR and INR by the mean warfarin
      dose. Four groups were compared by age: < 50, 50 to 59, 60 to 69, and > or = 70.
      A total of 243 charts were reviewed: 113 female, 130 male; 90% were Hispanic. The
      most common indication for anticoagulation was atrial fibrillation. Elderly
      patients had more medical problems (3.1 vs. 2.4) and took more medications (3.4
      vs. 2.4) than younger patients. The dose-adjusted PTR and dose-adjusted INR
      increased with aging (0.59 vs. 0.38 and 0.85 vs. 0.59, p < .05 ANOVA). In a
      multiple linear regression analysis, only age remained significantly associated
      with the anticoagulant effect. These results are consistent with previous reports
      on the effect of warfarin in aging patients and extend these data to the Hispanic
      population.

PMID- 11831537
TI  - A simplified method for detecting isoniazid compliance in patients receiving
      antituberculosis chemotherapy.
AB  - The objective of this study was to develop a new simplified method using thin
      layer chromatography (TLC) for determining isoniazid (INH) compliance in patients
      receiving antituberculosis chemotherapy. TLC was performed on silica gel plates
      using a standard solution of INH and acetylisoniazid (AcINH) and ethyl acetate
      methanol (70:30 v/v) as the developing solvent. The spots of compound were
      detected by iodine. In the human study, fractional urine samples were collected
      over 24 hours from 4 healthy human subjects genotyped for NAT2* and to whom 400
      mg of INH were administered orally. These samples were used for TLC analysis. The
      results of TLC were compared with those of high-performance liquid chromatography
      (HPLC). This method indicated good separation between INH and AcINH in standard
      solutions. The detection limits for INH and AcINH (applied volume; 20 microl of
      standard solution) were 2.2 nmole and 5 nmole, respectively, as detected by
      iodine. In the human study, the INH spot in urine was not detected on the TLC
      plate, except in one sample over the 0- to 4-hour period from 1 volunteer.
      However, the AcINH spot was detected in all urine samples from all volunteers.
      The total experimental time from application of the urine sample to analysis on
      TLC was 30 minutes. The results suggest that this method for detecting AcINH on
      TLC is an excellent, convenient, and simple method for determining INH compliance
      in patients receiving standard antituberculosis chemotherapy regimen or INH
      preventative therapy, regardless of the patient's NAT2* genotype.

PMID- 11831538
TI  - Multiple-dose, safety, pharmacokinetics, and pharmacodynamics of a new selective
      estrogen receptor modulator, ERA-923, in healthy postmenopausal women.
AB  - ERA-923 is a new selective estrogen receptor modulator under clinical
      investigation for use in tamoxifen refractory metastatic breast cancer. This
      study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics
      of once-daily oral ERA-923 (10-200 mg) for 28 days in healthy postmenopausal
      females. ERA-923 was well tolerated, and adverse events were mild and reversible.
      No clinically significant changes in laboratory values were found with ERA-923
      versus placebo. ERA-923 appeared to undergo extensive metabolism and
      enterohepatic recirculation. In addition, pharmacokinetic analysis showed that a
      high-fat breakfast increased the extent of absorption. ERA-923-dosed subjects had
      no uterine or ovarian changes when evaluated with transvaginal ultrasound and
      compared to placebo subjects. Overall, ERA-923 was safe and well tolerated in
      postmenopausal women dosed for 28 days.

PMID- 11831539
TI  - New dosing regimens for amifostine: a pilot study to compare the relative
      bioavailability of oral and subcutaneous administration with intravenous
      infusion.
AB  - A phase I clinical trial was conducted to assess thefeasibility of a more
      convenient and safe dosing regime for the cytoprotective drug amifostine. Two
      alternative routes of administration, oral and subcutaneous (s.q.), each with a
      dose of 500 mg, were compared to a 7.5-minute intravenous (i.v.) infusion, with a
      dose of 200 mg/m2, in normal, healthy volunteers (N = 12). Bioavailability of
      amifostine (parent drug) and its pharmacologically active metabolite, WR-1065,
      was evaluated by comparing the area under the concentration-time curve (AUC)
      derived from HPLC analysis of amifostine and both protein-free and protein-bound
      WR-1065 in all three routes of administration. Results showed that SQ (but not
      oral) administration of amifostine could provide a more effective dosing regimen,
      in terms of both a reasonable AUC for the bound form of WR-1065 and decreased
      toxicity, compared to i.v. delivery. These data suggest that the protein-bound
      form of WR-1065 plays an important role in contributing to the bioavailability of
      this clinically useful cytoprotective drug.

PMID- 11831540
TI  - Multiple-dose, linear, dose-proportional pharmacokinetics of retigabine in
      healthy volunteers.
AB  - Retigabine, a first-in-class selective M-current potassium channel opener, is a
      novel antiepileptic compound currently in clinical development. The purpose of
      this randomized placebo-controlled study was to assess retigabine oral safety and
      pharmacokinetics in healthy male volunteers (N = 45). Subjects received one dose
      on day 1 and doses every 12 hours for the next 14 days. Fixed doses were given to
      the first four groups (200, 400, 500, and 600 mg per day). Titrated doses were
      given to group 5 in 100 mg increases every 4 days, achieving 700 mg per day on
      day 15. Serial blood samples were collected on days 1 and 15. Pharmacokinetic
      parameters were compared between days and among dose groups. After administration
      of a single dose, retigabine was rapidly absorbed, with maximum concentrations of
      387 ng/ml (normalized to a 100 mg dose) occurring within 1.5 hours. Retigabine
      was eliminated with a mean terminal half-life of 8.0 hours and an apparent oral
      clearance of 0.70 L/h/kg in white subjects. In black subjects, retigabine
      clearance and volume of distribution were 25% and 30% lower, respectively, after
      normalizing by body weight, leading to higher exposure in this population.
      Retigabine's pharmocokinetics was linearly dose proportional. Steady-state
      pharmacokinetics was in agreement with single-dose pharmacokinetics, and the
      accumulation ratio was about 1.5. Retigabine and AWD21-360 trough evening
      concentrations were significantly lower (about 30% to 35%) than morning values.
      The titration regimen allowed for higher doses to be tolerated compared to the
      fixed-dose regimen. In conclusion, the pharmacokinetics of retigabine is linearly
      dose proportional for daily doses of 100 to 700 mg and is not modified on
      multiple administrations.

PMID- 11831541
TI  - Effect of fluconazole on the pharmacokinetics and pharmacodynamics of oral and
      rectal bromazepam: an application of electroencephalography as the
      pharmacodynamic method.
AB  - Quantitative analysis of electroencephalography (EEG) is used increasingly to
      evaluate the pharmacodynamics of benzodiazepines. The present study aimed to
      apply the EEG method as well as more traditional approaches to an interaction
      study of bromazepam and fluconazole. Twelve healthy male volunteers participated
      in a randomized, double-blind, four-way crossover study. The subjects received
      single oral or rectal doses of bromazepam (3 mg) after 4-day pretreatment of oral
      fluconazole (100 mg daily) or its placebo. Plasma bromazepam concentrations were
      measured before and 0.5, 1, 2, 3, 4, 6, 12, 22, 46, and 70 hours after bromazepam
      administration. Pharmacodynamic effects of bromazepam were assessed using self
      rated drowsiness, continuous number addition test, and EEG. Fluconazole caused no
      significant changes in pharmacokinetics and pharmacodynamics of oral or rectal
      bromazepam. Rectal administration significantly increased AUC (1.7-fold, p <
      0.0001) and Cmax (1.6-fold, p < 0.0001) of bromazepam. These changes following
      rectal dose may be due to avoidance of degradation occurring in the
      gastrointestinal tract. Rectal bromazepam also increased the area under the
      effect curves assessed by EEG (p < 0.05) and subjective drowsiness (p < 0.05).
      EEG effects were closely correlated with mean plasma bromazepam concentrations (r
      = 0.92, p < 0.001 for placebo; r = 0.89, p < 0.0001 for fluconazole). Thus, the
      EEG method provided pharmacodynamic data that clearly reflected the
      pharmacokinetics of bromazepam.

PMID- 11831542
TI  - Comparison of the pharmacokinetics of oxycodone administered in three Percocet
      formulations.
AB  - This randomized, open-label, three-period crossover study compared the single
      dose pharmacokinetics of three dose levels of oxycodone in combination with
      acetaminophen (5 mg/325 mg, 7.5 mg/500 mg, or 10 mg/650 mg) in healthy
      volunteers. Serial 24-hour blood samples were collectedfrom 23 fasting subjects
      after drug administration. The individual dose levels were evaluated on 3
      different days, which were separated by washout periods of at least 7 days, in
      each subject. Oxycodone AUC(0-t), AUC(0-infinity), and Cmax were dose dependent,
      whereas tma and t(1/2) were not. The most frequently reported adverse events were
      dizziness, nausea, headache, pruritus, and vomiting. Most adverse events were
      mild, and all were self-limiting. Only dizziness occurred in a dose-related
      manner. Increasing dose levels of oxycodone/acetaminophen provides proportional
      increases in oxycodone Cmax and AUC. Adverse events were predictable based on the
      opioid pharmacologic actions of this agent.

PMID- 11831543
TI  - Comparative pharmacokinetics of lovastatin extended-release tablets and
      lovastatin immediate-release tablets in humans.
AB  - The pharmacokinetics of lovastatin and its active metabolite lovastatin acid was
      evaluated in 9 healthy subjects in a three-period crossover study following a
      single oral dose of lovastatin extended-release (ER) tablets and lovastatin
      immediate-release (IR) tablets. Participants were dosed with lovastatin IR 40 mg
      tablets following a standard breakfast, lovastatin ER 40 mg tablets following a
      standard breakfast, and lovastatin ER 40 mg tablets underfasting conditions.
      Serial plasma samples were collected for up to 48 hours postdose and assayed for
      lovastatin and lovastatin acid using a liquid chromatography/mass
      spectroscopy/mass spectroscopy method. Lovastatin ER tablets, unlike lovastatin
      IR tablets, exhibited delayed- and extended-release characteristics. The relative
      bioavailability, in terms of area under the curve values, of lovastatin (156%)
      and lovastatin acid (124%) was greater from lovastatin ER tablets as compared
      with lovastatin IR tablets when given with breakfast. An even greater increase in
      the bioavailability of lovastatin (261%) and lovastatin acid (231%) was observed
      when the lovastatin ER tablets were administered under fasting conditions. Thus,
      greater gastrointestinal tract drug absorption of lovastatin from lovastatin ER
      tablets was demonstrated. Ingestion of a standard breakfast prior to
      administration of lovastatin ER tablets decreased absorption of lovastatin by
      approximately 40%, relative to lovastatin ER tablets under fasting conditions.

PMID- 11831544
TI  - Effect of modafinil at steady state on the single-dose pharmacokinetic profile of
      warfarin in healthy volunteers.
AB  - Modafinil has been reported to produce a concentration-related suppression of
      CYP2C9 activity in vitro in primary cultures of human hepatocytes. To determine
      whether this effect occurs in vivo, the pharmacokinetics of (S)-warfarin was
      investigated after single oral doses of racemic warfarin (5 mg; COUMADIN) in a
      placebo-controlled, single-blind, single-period study in 28 volunteers. Subjects
      received an oral dose of warfarin prior to administration of modafinil (200 mg
      for 7 days, followed by 400 mg for 21 days) or placebo and they received another
      after 4 weeks of treatment. Treatment with modafinil did not significantly alter
      the pharmacokinetics of (S)- or (R)-warfarin relative to placebo. Since (S)
      warfarin is predominantly metabolized via CYP2C9, the results indicate that the
      marked suppression of CYP2C9 activity in vitro does not translate into a similar
      effect clinically. However, limitations arising from investigation of single
      doses of warfarin preclude global conclusions about the potential for more subtle
      interactions after chronic warfarin administration.

PMID- 11831545
TI  - Effect of rofecoxib on the pharmacokinetics of chronically administered oral
      contraceptives in healthy female volunteers.
AB  - The effect of rofecoxib, a highly selective cyclooxygenase (COX)-2 inhibitor, on
      the pharmacokinetics of ethinyl estradiol (EE) and norethindrone (NET), two
      common components of a combination oral contraceptive product, was examined. A
      double-blind, two-period crossover study was conducted in 18 healthy women who
      received ORTHO-NOVUM 1/35, a combination of EE (35 microg) and NET (1 mg),
      concurrently for 14 days with either 175 mg rofecoxib or matching placebo during
      two consecutive menstrual cycles. Plasma was sampled for EE, NET, sex hormone
      binding globulin (SHBG), and albumin. The AUC(0-24 h) geometric mean ratio (GMR:
      rofecoxib/placebo) with corresponding 90% confidence interval (CI) of EE and NET
      was 1.13 (1.06, 1.19) and 1.18 (1.13, 1.24), respectively. The Cmax GMR of EE and
      NET was 1.06 (0.98, 1.16) and 1.04 (0.99, 1.09), respectively. In each case, the
      90% CIs satisfied the predefined bioequivalence limits of (0.80, 1.25). Measures
      of SHBG and albumin and routine clinical and laboratory safety parameters showed
      no clinically meaningful changes. The addition of rofecoxib to the oral
      contraceptive was not associated with any clinically important changes in EE or
      NET pharmacokinetics and thus would not be anticipated to influence the efficacy
      of this contraceptive regimen.

PMID- 11831546
TI  - Pharmacokinetic and pharmacodynamic assessments of HMG-CoA reductase inhibitors
      when coadministered with everolimus.
AB  - The authors assessed the mutual influence of the immunosuppressant everolimus
      (Certican) and the HMG-CoA reductase inhibitors atorvastatin and pravastatin when
      coadministered based on pharmacokinetic and pharmacodynamic measures. In this
      randomized, open-label, three-way crossover study, 24 healthy men received three
      single-dose oral treatments: 2 mg everolimus, 20 mg atorvastatin (n = 12) or 20
      mg pravastatin (n = 12), and the respective statin coadministered with
      everolimus. Consecutive treatments were separated by a 14-day washout. The
      pharmacokinetics of all three drugs and total HMG-CoA reductase inhibitors were
      measured. Everolimus Cmax was reduced by 9% and 10% with atorvastatin and
      pravastatin coadministration; the corresponding decreases in everolimus AUC were
      5% and 6%, respectively. Everolimus coadministration increased the Cmax of
      atorvastatin by 11% but had no influence on atorvastatin AUC. Coadministration of
      everolimus with pravastatin was associated with a 10% decrease in pravastatin
      Cmax and a 5% decrease in the AUC. The elimination half-lives of the two statins
      were unaffected by everolimus. Changes in total HMG-CoA reductase inhibitors in
      plasma exhibited generally similar patterns as for the parent statin exposures.
      Single-dose administrations of everolimus with either atorvastatin or pravastatin
      did not influence the pharmacokinetics of everolimus, atorvastatin, pravastatin,
      or total HMG-CoA reductase inhibitors in plasma to a clinically relevant extent.

PMID- 11831547
TI  - Anterograde axonal transport, transcytosis, and recycling of neurotrophic
      factors: the concept of trophic currencies in neural networks.
AB  - Traditional views of neurotrophic factor biology held that trophic factors are
      released from target cells, retrogradely transported along their axons, and
      rapidly degraded upon arrival in cell bodies. Increasing evidence indicates that
      several trophic factors such as brain-derived neurotrophic factor (BDNF),
      fibroblast growth factor (FGF-2), glial cell-line derived neurotrophic factor
      (GDNF), insulin-like growth factor (IGF-I), and neurotrophin-3 (NT-3), can move
      anterogradely along axons. They can escape the degradative pathway upon
      internalization and are recycled for future uses. Internalized ligands can move
      through intermediary cells by transcytosis, presumably by endocytosis via
      endosomes to the Golgi system, by trafficking of the factor to dendrites or by
      sorting into anterograde axonal transport with subsequent release from axon
      terminals and uptake by second- or third-order target neurons. Such data suggest
      the existence of multiple "trophic currencies," which may be used over several
      steps in neural networks to enable nurturing relationships between connected
      neurons or glial cells, not unlike currency exchanges between trading partners in
      the world economy. Functions of multistep transfer of trophic material through
      neural networks may include regulation of neuronal survival, differentiation of
      phenotypes and dendritic morphology, synapse plasticity, as well as excitatory
      neurotransmission. The molecular mechanisms of sorting, trafficking, and release
      of trophic factors from distinct neuronal compartments are important for an
      understanding of neurotrophism, but they present challenging tasks owing to the
      low levels of the endogenous factors.

PMID- 11831549
TI  - Caspase-dependent apoptotic pathways in CNS injury.
AB  - Recent studies have suggested a role for neuronal apoptosis in cell loss
      following acute CNS injury as well as in chronic neurodegeneration. Caspases are
      a family of cysteine requiring aspartate proteases with sequence similarity to
      Ced-3 protein of Caenorhabditis elegans. These proteases have been found to
      contribute significantly to the morphological and biochemical manifestations of
      apoptotic cell death. Caspases are translated as inactive zymogens and become
      active after specific cleavage. Of the 14 identified caspases, caspase-3 appears
      to be the major effector of neuronal apoptosis induced by a variety of stimuli. A
      role for caspase-3 in injury-induced neuronal cell death has been established
      using semispecific peptide caspase inhibitors. This article reviews the current
      literature relating to pathways regulating caspase activation in apoptosis
      associated with acute and chronic neurodegeneration, and suggests that
      identification of critical upstream caspase regulatory mechanisms may permit more
      effective treatment of such disorders.

PMID- 11831548
TI  - Molecular mechanisms of glutamate receptor-mediated excitotoxic neuronal cell
      death.
AB  - Excitotoxicity is one of the most extensively studied processes of neuronal cell
      death, and plays an important role in many central nervous system (CNS) diseases,
      including CNS ischemia, trauma, and neurodegenerative disorders. First described
      by Olney, excitotoxicity was later characterized as an excessive synaptic release
      of glutamate, which in turn activates postsynaptic glutamate receptors. While
      almost every glutamate receptor subtype has been implicated in mediating
      excitotoxic cell death, it is generally accepted that the N-methyl-D-aspartate
      (NMDA) subtypes play a major role, mainly owing to their high calcium (Ca2+)
      permeability. However, other glutamate receptor subtypes such as 2-amino-3-(3
      hydroxy-5-methylisoxazol-4-yl) propionate (AMPA) or kainate receptors have also
      been attributed a critical role in mediating excitotoxic neuronal cell death.
      Although the molecular basis of glutamate toxicity is uncertain, there is general
      agreement that it is in large part Ca(2+)-dependent. The present review is aimed
      at summarizing the molecular mechanisms of NMDA receptor and AMPA/kainate
      receptor-mediated excitotoxic neuronal cell death.

PMID- 11831550
TI  - Paradoxical signal transduction in neurobiological systems.
AB  - Information processing in neurobiological systems is commonly thought to rely on
      the assessment of a signal-to-noise ratio as the key mechanism of signal
      detection; it assumes and requires that both signal and noise are concurrently
      available. An alternative theory holds that detection proceeds by the system
      appreciating any instantaneous input by the input's departure from the moving
      average of past activity. The evidence reviewed here suggests that this latter
      transduction mechanism provides a unique, formal account of the highly dynamic,
      neuroadaptative plasticity (i.e., tolerance, dependence, sensitization) that
      ensues upon mu-opioid receptor activation. The mechanism would appear already to
      operate with the receptor-G protein coupling that occurs upon agonist binding to
      mu-opioid receptors, and also with highly integrated responses such as whole
      organism analgesia. The mechanism may perhaps operate ubiquitously with further
      neuronal and non-neuronal, cell surface, and intracellular-signaling systems, and
      may govern the experience-dependent regulation of synaptic strength. The
      transduction mechanism defines a continuously evolving process; the process's
      most peculiar feature is that it makes any input generate not one but two
      outcomes that are paradoxical, or opposite in sign.

PMID- 11831551
TI  - The duality of the inflammatory response to traumatic brain injury.
AB  - One and a half to two million people sustain a traumatic brain injury (TBI) in
      the US each year, of which approx 70,000-90,000 will suffer from long-term
      disability with dramatic impacts on their own and their families' lives and
      enormous socio-economic costs. Brain damage following traumatic injury is a
      result of direct (immediate mechanical disruption of brain tissue, or primary
      injury) and indirect (secondary or delayed) mechanisms. These secondary
      mechanisms involve the initiation of an acute inflammatory response, including
      breakdown of the blood-brain barrier (BBB), edema formation and swelling,
      infiltration of peripheral blood cells and activation of resident immunocompetent
      cells, as well as the intrathecal release of numerous immune mediators such as
      interleukins and chemotactic factors. An overview over the inflammatory response
      to trauma as observed in clinical and in experimental TBI is presented in this
      review. The possibly harmful/beneficial sequelae of post-traumatic inflammation
      in the central nervous system (CNS) are discussed using three model mediators of
      inflammation in the brain, tumor necrosis factor-alpha (TNF-alpha), interleukin-6
      (IL-6), and transforming growth factor-beta (TGF-beta). While the former two may
      act as important mediators for the initiation and the support of post-traumatic
      inflammation, thus causing additional cell death and neurologic dysfunction, they
      may also pave the way for reparative processes. TGF-beta, on the other hand, is a
      potent anti-inflammatory agent, which may also have some deleterious long-term
      effects in the injured brain. The implications of this duality of the post
      traumatic inflammatory response for the treatment of brain-injured patients using
      anti-inflammatory strategies are discussed.

PMID- 11831552
TI  - Nerve growth factor: a neurokine orchestrating neuroimmune-endocrine functions.
AB  - Nerve growth factor (NGF) is widely recognized as a target-derived factor
      responsible for the survival and maintenance of the phenotype of specific subsets
      of peripheral neurons and basal forebrain cholinergic nuclei during development
      and maturation. Other NGF-responsive cells are now known to belong to the
      hemopoietic-immune system and to populations in the brain involved in
      neuroendocrine functions. The concentration of NGF is elevated in a number of
      inflammatory and autoimmune states in conjunction with increased accumulation of
      mast cells. Mast cells and NGF appear to be involved in neuroimmune interactions
      and tissue inflammation. Mast cells themselves are capable of producing and
      responding to NGF, suggesting that alterations in mast cell behavior may trigger
      maladaptive neuroimmune tissue responses, including those of an autoimmune
      nature. Moreover, NGF exerts a modulatory role on sensory nociceptive nerve
      physiology in the adult, and appears to correlate with hyperalgesic phenomena
      occurring in tissue inflammation. NGF can thus be viewed as a multifactorial
      modulator of neuroimmune-endocrine functions.

PMID- 11831554
TI  - Revisiting the function of PSA-NCAM in the nervous system.
AB  - Since its first description the polysialylated form of NCAM (PSA-NCAM) is thought
      to be a major regulator of cell-cell interactions in the nervous system. Over the
      past few years many crucial questions have been answered concerning PSA
      biosynthesis and function. Among these are the identification and cloning of the
      key enzymes that are responsible for its synthesis and the fact that expression
      of PSA is not restricted to developmental stages but maintained in the adult
      nervous system. In the adult, PSA has been shown to be not only a marker of
      structural plasticity but seems to be a major player in these processes.
      Originally suggested to be a purely anti-adhesive factor, modulating cell-cell
      interactions in general and by this allowing plasticity, there is now increasing
      evidence that this might not be the whole story. Instead, it appears possible
      that PSA-NCAM interacts with secreted signaling molecules and by this fulfills a
      more instructive function in brain plasticity.

PMID- 11831553
TI  - Cannabinoids and neuroprotection.
AB  - Cannabinoid compounds are endowed with pharmacological properties that make them
      interesting candidates for therapeutic development. These properties have been
      known since antiquity. However, in the last decade extremely important advances
      in the understanding of the physiology, pharmacology, and molecular biology of
      the cannabinoid system have given this field of research fresh impetus and have
      renewed the interest in the possible clinical exploitation of these compounds. In
      the present review we summarize the effects elicited, at the cellular level, by
      cannabinoids acting through receptor-dependent and receptor-independent
      mechanisms. These data suggest different ways by which cannabinoids may act as
      neuroprotective agents (prevention of excitotoxicity by inhibition of glutamate
      release, antioxidant effects, anti-inflammatory actions, etc.). The experimental
      evidence supporting these hypotheses are presented and discussed with regard to
      both preclinical and clinical studies in disease states such as cerebral
      ischemia, brain trauma, and Multiple Sclerosis.

PMID- 11831556
TI  - CSF total tau, Abeta42 and phosphorylated tau protein as biomarkers for
      Alzheimer's disease.
AB  - With the arrival of effective symptomatic treatments and the promise of drugs
      that may delay progression, we now need to identify Alzheimer's disease (AD) at
      an early stage of the disease. To diagnose AD earlier and more accurately,
      attention has been directed toward peripheral biochemical markers. This article
      reviews promising potential cerebrospinal fluid (CSF) biomarkers for AD focussing
      on their role in clinical diagnosis. In particular, two biochemical markers, CSF
      total tau (t-tau) protein and the 42 amino acid form of beta-amyloid (Abeta42),
      perform satisfactorily enough to achieve a role in the clinical diagnostic
      settings of patients with dementia together with the cumulative information from
      basic clinical work-up, genetic screening, and brain imaging. These CSF markers
      are particularly useful to discriminate early or incipient AD from age-associated
      memory impairment, depression, and some secondary dementias. In order to
      discriminate AD from other primary dementia disorders, however, more accurate and
      specific markers are needed. Preliminary evidence strongly suggests that
      quantification of tau phosphorylated at specific sites in CSF improves early
      detection, differential diagnosis, and tracking of disease progression in AD.

PMID- 11831558
TI  - Peptides as drugs: is there a market?

PMID- 11831555
TI  - Pharmacological modulation of intracellular Ca(2+) channels at the single-channel
      level.
AB  - Synaptic signaling, memory formation, neuronal development, and neuronal
      pathology are strongly influenced by the properties of intracellular Ca2+
      channels, ryanodine, and inositol 1, 4, 5 trisphosphate receptors. This review
      will focus on recently developed and discovered pharmacological tools to modulate
      these channel proteins at the single-channel level. It will allow the readers of
      Molecular Neurobiology to evaluate the current knowledge on the pharmacological
      modulation of intracellular Ca2+ channels and to direct future research efforts
      effectively using available experimental tools and concepts.

PMID- 11831559
TI  - Synthesis of oligopeptides with the sequence SXWS and their chemotactic effects
      on a ciliated protozoan Tetrahymena pyriformis.
AB  - In this paper, the solid phase synthesis and chemical characterization of members
      of an SXWS sub-library (SAWS, SDWS and SKWS) as well as the comparison of their
      chemotactic properties with those of SEWS, which exhibits a prominent effect at
      10(-12) M on a ciliated protozoan, Tetrahymena pyriformis, are described. We
      found that the chemotaxis of cells induced with the SXWS peptides varied
      according to the nature of the amino acid residue (Ala, Asp, Lys) in position X.
      The chemotactic activity of SEWS was not surpassed by any of three new
      tetrapeptides, although SAWS was also chemoattractant. Interestingly, SDWS, with
      an acidic side chain at position X, could not elicit any chemotactic response.
      SKWS, however, showed mild but significant chemorepellent activity over a wide
      concentration range. Chemotactic selection studies showed that the two
      chemoattractant peptides (SAWS and SEWS) had an expressed ability to select high
      responder offspring cell populations. Peptides with neutral (SDWS) or
      chemorepellent (SKWS) properties were not able to select such subpopulations from
      the mixed cultures of Tetrahymena, indicating that the chemotactic response
      elicited by SXWS peptides is ligand-specific. For ligand-binding experiments N
      terminally labelled fluorescent derivatives of SXWS peptides were prepared.
      applying [4-[7-hydroxycoumaryl]]acetic acid (Hca-OH) or 4-ethoxymethylene-2-[1]
      naphthyl-5(4H)-oxazolone (naOx-OEt) as markers. Hca-OH was introduced using an
      active ester technique as the last step of SPPS, or after cleavage in solution.
      The oxazolone naOx-OEt reacted with the amino group of the peptide by liberation
      of EtOH. The binding characteristics of fixed Tetrahymena cells with the naOx
      labelled peptides showed good correlation between binding profiles and
      chemotactic responsiveness (SEWS > SAWS > SDWS - SKWS). A similar binding pattern
      was observed in the case of Hca-peptides (SEWS > SAWS > SDWS). Hca-SKWS, however,
      bound remarkably to the cell surface. The binding activity of the Hca-peptides
      was less pronounced than that of the naOx-peptides, indicating the importance of
      the fluorophores applied.

PMID- 11831557
TI  - Zinc and disease of the brain.
AB  - Zinc is one of the most abundant transition metals in the brain. A substantial
      fraction (10-15%) of brain zinc is located inside presynaptic vesicles of certain
      glutamatergic terminals in a free or loosely bound state. This vesicle zinc is
      released with neuronal activity or depolarization, probably serving physiologic
      functions. However, with excess release, as may occur in a variety of pathologic
      conditions, zinc may translocate to and accumulate in postsynaptic neurons,
      events which may contribute to selective neuronal cell death. Intracellular
      mechanisms of zinc neurotoxicity may include disturbances in energy metabolism,
      increases in oxidative stress, and activation of apoptosis cascades. Zinc
      inhibits glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and depletes
      nicotinamide adenine dinucleotide (NAD(+)) and adenosine triphosphate (ATP). On
      the other hand, zinc activates protein kinase C (PKC) and extracellular signal
      regulated kinase (Erk-1/2), and induces NADPH oxidase; these events result in
      oxidative neuronal injury. Zinc can also trigger caspase activation and apoptosis
      via the p75(NTR) pathway. Interestingly, the converse-depletion of intracellular
      zinc-also induces neuronal death, but in this case, exclusively via classical
      apoptosis. In addition to the neurotoxic effect, zinc may contribute to the
      pathogenesis of chronic neurodegenerative disease. For example, in Alzheimer's
      disease (AD), mature amyloid plaques, but not preamyloid deposits, are found to
      contain high levels of zinc, suggesting the role of zinc in the process of plaque
      maturation. Further insights into roles of zinc in brain diseases may help set a
      new direction toward the development of effective treatments.

PMID- 11831560
TI  - The effects of charge and lipophilicity on the antibacterial activity of
      undecapeptides derived from bovine lactoferricin.
AB  - We have investigated the effects of charge and lipophilicity on the antibacterial
      activity of an undecapeptide (FKCRRWQWRMK) derived from the sequence of bovine
      lactoferricin. We prepared ten analogues that were modified by the incorporation
      of Ala, Tyr, Trp, Met and Arg residues, which are amino acids known to be
      important for the antibacterial activity of longer derivatives of lactoferricins.
      All undecapeptides contained the native Trp residues in positions 6 and 8, and
      the Arg residues in positions 5 and 9. Generally, the Gram-positive bacterium
      Staphylococcus aureus was more susceptible to these undecapeptides than the Gram
      negative bacteria, and a higher antibacterial activity was observed against
      Escherichia coli than against Pseudomonas aeruginosa. The only exception was the
      peptide Undeca 9 (RRWYRWAWRMR-NH2), which was almost equally active against all
      three test strains, displaying minimal inhibitory concentrations of 10 microg/ml
      (5.8 microM), 7.5 microg/ml (4.4 microM) and 5 microg/ml (2.9 microM) against
      Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus, respectively.
      The peptides Undeca 6 (YRAWRWAWRWR-NH2) and Undeca 7 (YRMWRWAWRWR-NH2) were the
      two most active undecapeptides against Staphylococcus aureus, both displaying a
      minimal inhibitory concentration of 2.5 microg/ml (1.5 microM). The study showed
      that a level was reached in which undecapeptides having a net charge above +4 and
      containing three or four Trp residues all displayed a high antibacterial
      activity. All undecapeptides prepared were essentially non-haemolytic, but
      undecapeptides containing more than three Trp residues displayed 50% haemolysis
      of human red blood cells at concentrations above 400 microg/ml (>230 microM).

PMID- 11831562
TI  - Frontal lobes and executive function.

PMID- 11831561
TI  - Catechol as a nucleophilic catalyst of peptide bond formation.
AB  - The aminolysis of a mildly activated aminoacid ester, benzyloxycarbonyl-L
      phenylalanine cyanomethyl ester, by glycine esters in the presence of catechol
      has been studied as a model of catalysis by RNA cis-vicinal-diol systems in
      protein biosynthesis. Catechol accelerated the aminolysis, especially in the
      presence of bases, probably by nucleophilic catalysis.

PMID- 11831563
TI  - Learning difficulties in children treated for acute lymphoblastic leukaemia
      (ALL).
AB  - Concern about the adverse affects of brain irradiation used in treatment for
      childhood leukaemia on children's learning have been put forward since the 1960s.
      Early work based on assessment of IQ suggested considerable problems associated
      with CNS irradiation of 2400cGy, and that children who were younger on diagnosis
      (below 5 years) were particularly at risk. Consequently, new protocols were
      introduced in which the amount of irradiation was reduced, or children were
      treated by chemotherapy alone. There is some evidence that reduction from 2400 to
      1800cGy irradiation is beneficial, especially for younger children, as is
      treatment by chemotherapy alone. Methodological problems in conducting this work
      and limitations in relying on IQ tests are discussed. Where there are no
      indications of differences in survival, there would seem to be implications for
      reducing as far as possible the use of CNS directed therapy among young children
      treated for leukaemia.

PMID- 11831564
TI  - Assessing executive functions in children: biological, psychological, and
      developmental considerationst.
AB  - Executive functions may be defined as those skills necessary for purposeful, goal
      directed activity, and are generally considered to be largely mediated by the
      frontal and prefrontal cortices of the brain. These cerebral regions are
      relatively immature during childhood, with development thought to be a protracted
      process which continues into early adolescence. While early theorists suggested
      that executive skills were not functional until cerebral maturity, recent
      research provides evidence that such skills can be elicited in early childhood.
      The aim of this paper is to review current theories of development of executive
      functions throughout childhood. In keeping with contemporary approaches to child
      neuropsychology, three critical dimensions will be evaluated; biological factors,
      psychological dimensions, and developmental trajectories. In addition, the
      literature which addresses assessment of these functions will be examined, with
      reference to developmental trajectories observed in normal populations, and in
      brain-damaged samples, where there may be disruption to the underlying neural
      substrates thought to be subsuming these functions.

PMID- 11831565
TI  - The role of music therapy in paediatric rehabilitation.
AB  - Meeting the needs of the child in rehabilitation requires an interdisciplinary
      approach, whereby a variety of health care professionals are called upon to work
      together in planning and coordinating each patient's programme. The Registered
      music therapist is one of the allied health professionals who plays an integral
      role in this team approach. Music therapy is a recognized allied health
      profession, which is becoming acknowledged in the expanding world of health care
      as a therapy able to meet the expansive needs of the patient in rehabilitation.
      This article will present a literature review which advocates the role of music
      therapy in rehabilitation, with particular focus on the needs of the paediatric
      patient. Case vignettes will be used as further evidence to support the role of
      music therapy in this context, together with considerations for future research.

PMID- 11831566
TI  - Is physical exercise good for the brain of a child?

PMID- 11831567
TI  - In stereotactic radiosurgery, implanted fiducials are superior to an external
      coordinate system. For the proposition.

PMID- 11831569
TI  - Accelerator-based neutron brachytherapy.
AB  - The development and evaluation of a new approach to neutron brachytherapy is
      described. This approach, accelerator-based fast neutron brachytherapy, involves
      the interstitial or intracavity insertion of a narrow, evacuated accelerator beam
      tube such that its tip, containing the neutron-producing target, is placed in or
      near the tumor. Tumor irradiation via brachytherapy should result in a reduction
      in the healthy tissue complication rate observed when poorly collimated and/or
      low energy external neutron beam are used for treatment. Use of a variable energy
      accelerator provides an advantage over isotope sources for neutron brachytherapy
      in that the neutron beam can be turned on and off and the neutron energy spectrum
      varied for different treatment applications. A prototype accelerator-based fast
      neutron brachytherapy device, 10 cm long and 6 mm outer diameter, has been
      constructed and evaluated in terms of its dosimetric output, treatment time, and
      practical feasibility. The prototype device is a tube-in-tube design with cooling
      water running between the inner and outer tubes to cool a beryllium target
      located at the tip of the inner tube. Cooling experiments were performed and
      coupled with Monte Carlo simulations to determine treatment times as a function
      of heat load for various neutron-producing reactions. Using the 9Be(d,n) 10B
      reaction at Ed= 1.5 MeV, 66 RBE-Gy (12 Gy physical dose) can be delivered to the
      boundary of a 4.5-cm-diam treatment volume in 8 min at a heat load of 130 W.
      Other reactions offer similar treatment times at somewhat higher bombarding
      energies and also show higher potential for dose enhancement with the boron-10
      neutron capture reaction due to their softer neutron spectra. Dose distributions
      in a water phantom were measured with the prototype brachytherapy tube using the
      dual-ion chamber technique for the 9Be(d,n) 10B reaction at Ed = 1.5 MeV. The
      measurements and simulations agree within uncertainties and demonstrate that fast
      neutrons contribute more than 90% of the dose to the target volume.

PMID- 11831570
TI  - A method for physically based radiotherapy optimization with intelligent tissue
      weight determination.
AB  - An important aspect of the intensity modulated radiotherapy (IMRT) process is
      that of optimizing the beam intensity profiles. Most such methods use a
      comparison between the defined dose distribution (including prescription dose and
      dose limits for critical structures) and the current distribution. The comparison
      may involve dose differences or dose ratios. This paper investigates four
      different ratio-based methods, with a hypothetical U-shaped target and
      cylindrical phantom as the test case. All methods are shown to give satisfactory
      results. There are differences in the dose distributions produced and these can
      be related to the formulation of the respective fluence-update methods. In common
      with other IMRT beam optimization methods the techniques used here include tissue
      weighting factors which express the relative importance of achieving the goal
      dose level or limit. Altering the values of these weights can improve the ability
      of the optimization algorithm to adhere to the goal dose levels. Typically the
      weights are adjusted on a "trial and error" basis until the planner is satisfied
      with the results. In this paper a technique for automatic updating of the weights
      according to the optimization results is applied to each of the four fluence
      update methods. With this technique the difference between the current dose level
      in each tissue and the specified dose constant for that tissue is used to
      increase the weight should the constraint not be met. It is found that the four
      methods yield similar results if the weights are updated in this way.

PMID- 11831571
TI  - Improvement of dose distributions in abutment regions of intensity modulated
      radiation therapy and electron fields.
AB  - In recent years, intensity modulated radiation therapy (IMRT) is used to radiate
      tumors that are in close proximity to vital organs. Targets consisting of a deep
      seated region followed by a superficial one may be treated with abutting photon
      and electron fields. However, no systematic study regarding matching of IMRT and
      electron beams was reported. In this work, a study of dose distributions in the
      abutment region between tomographic and step-and-shoot IMRT and electron fields
      was carried out. A method that significantly improves dose homogeneity between
      abutting tomographic IMRT and electron fields was developed and tested. In this
      method, a target region that is covered by IMRT was extended into the superficial
      target area by approximately 2.0 cm. The length and shape of IMRT target
      extension was chosen such that high isodose lines bent away from the region
      treated by the electrons. This reduced the magnitude of hot spots caused by the
      "bulging effect" of electron field penumbra. To account for the uncertainties in
      positioning of the IMRT and electron fields, electron field penumbra was modified
      using conventional (photon) multileaf collimator (MLC). The electron beam was
      delivered in two steps: half of the dose delivered with MLCs in retracted
      position and another half with MLCs extended to the edge of electron field that
      abuts tomographic IMRT field. The experimental testing of this method using film
      dosimetry has demonstrated that the magnitude of the hot spots was reduced from
      approximately 45% to approximately 5% of the prescription dose. When an error of
      +/- 1.5 mm in field positioning was introduced, the dose inhomogeneity in the
      abutment region did not exceed +/- 15% of the prescription dose. With step-and
      shoot IMRT, the most homogeneous dose distribution was achieved when there was a
      3 mm gap between the IMRT and electron fields.

PMID- 11831572
TI  - Clearance assurance for stereotactic radiosurgery and radiotherapy.
AB  - The nature of stereotactic radiotherapy (SRT)/radiosurgery (SRS) requires the use
      of oblique non-coplanar beams to avoid critical structures and maximize target
      coverage. These beams are delivered via a combination of gantry, collimator, and
      couch rotations. Such beam orientations could result in the gantry colliding with
      the patient or couch. The outcome can be patient injury, damaged equipment, and
      unrealized treatment. Our objective in this work was to create a treatment
      planning tool that utilizes each unique patient geometry to quantify clearance
      for stereotactic beams. Emphasis was placed on developing a general platform that
      can completely, yet easily, define any user system. Gantry components were
      described by providing component dimensions to software that generates thousands
      of surface points. Table components were described as a combination of boxes and
      measured surface points. During the treatment planning process isocenter
      coordinates, patient dimensions and beam orientation were specified. Gantry
      components were then transformed into the table reference frame. The shortest
      distance between the gantry and patient or couch was computed and compared to a
      safety margin. This clearance assurance algorithm was developed in response to
      the need to reduce patient setup time, and to increase the range of potentially
      useful beams. The software was verified by measuring minimum gantry-table
      distances at multiple beam orientations and comparing to calculations.
      Differences between calculated and measured clearances were on the order of 1 cm.
      The software enabled the safe delivery of noncoplanar oblique beams that are
      difficult to visualize. The software was used successfully to assure clearance
      for 50 patients (366 beams). This useful clinical tool became an integral part of
      the stereotactic quality assurance protocol at St Luke's-Roosevelt Hospital
      Center.

PMID- 11831573
TI  - Artifact analysis of approximate helical cone-beam CT reconstruction algorithms.
AB  - In this paper, four approximate cone-beam CT reconstruction algorithms are
      compared: Advanced single slice rebinning (ASSR) as a representative of
      algorithms employing a two dimensional approximation, PI, PI-SLANT, and 3-PI
      which all use a proper three dimensional back-projection. A detailed analysis of
      the image artifacts produced by these techniques shows that aliasing in the z
      direction is the predominant source of artifacts for a 16-row scanner with 1.25
      mm nominal slice thickness. For a detector with isotropic resolution of 0.5 mm,
      we found that ASSR and PI produce different kinds of artifacts which are almost
      at the same level, while PI-SLANT produces none of these artifacts. It is shown
      that the use of redundant data in the 3-PI method suppresses aliasing artifacts
      efficiently for both scanners.

PMID- 11831574
TI  - Site-specific variability in trabecular bone dosimetry: considerations of energy
      loss to cortical bone.
AB  - With continual advances in radionuclide therapies, increasing emphasis is being
      placed on improving the patient specificity of dose estimates to marrow tissues.
      While much work has been focused on determining patient-specific assessments of
      radionuclide uptake in the skeleton, few studies have been initiated to explore
      the individual variability of absorbed fraction data for electron and beta
      particle sources in various skeletal sites. The most recent values of
      radionuclide S values used in clinical medicine continue to utilize a formalism
      in which electrons are transported under a trabecular bone geometry of infinite
      extent. No provisions are thus made for the fraction of energy lost to the
      cortical bone cortex of the skeletal site and its surrounding tissues. In the
      present study, NMR microscopy was performed on trabecular bone samples taken from
      the femoral head and humeral proximal epiphysis of three subjects: a 51-year
      male, an 82-year female, and an 86-year female. Following image segmentation and
      coupling to EGS4, electrons were transported within macrostructural models of the
      various skeletal sites that explicitly include the spatial extent of the
      spongiosa, as well as the thickness of the surrounding cortical bone. These
      energy-dependent profiles of absorbed fractions to marrow tissues were then
      compared to transport simulations made within an infinite region of spongiosa.
      Ratios of mean absorbed fraction, as weighted by the beta energy spectra, under
      both transport methodologies were then assembled for the radionuclides 32P and
      90Y. These ratios indicate that corrections to existing radionuclide S values for
      32P can vary by as much as 5% for the male, 6% for the 82-year female, and 8% for
      the 86-year female. For the higher-energy beta spectrum of 90Y, these same
      corrections can reach 8%, 10%, and 11%, respectively.

PMID- 11831575
TI  - MR validation of soft tissue mimicing phantom deformation as modeled by nonlinear
      finite element analysis.
AB  - A study of the applicability of nonlinear finite element analysis (FEA) to
      predict soft tissue deformation was validated with phase contrast magnetic
      resonance velocity imaging. A phantom of varying stiffness was placed in a
      special purpose, computer controlled MR compatible compression apparatus which
      provided precise, time varying compression with surface deformations on the order
      of 11%. The resulting motion was measured with MR velocity images acquired
      throughout the cycle of compression. The phantom geometry was modeled with a
      finite element mesh and the mechanical properties of the phantom material were
      measured and incorporated in the FEA model. The motion as calculated by the FEA
      model was compared to the motion measured with MRI and the results were found to
      vary with the material's Poisson's ratio and the coefficient of friction. A
      minimum difference was reached when the Poisson's ratio and coefficient of
      friction were set to 0.485 and 0.3, respectively. Under these conditions, the
      root mean square difference was found to be 14.4%.

PMID- 11831576
TI  - Modulation transfer function of digitally reconstructed radiographs using helical
      computed tomography.
AB  - We have measured the modulation transfer function (MTF), at a distance from CT
      isocenter, in digitally reconstructed radiographs (DRR) using a bar pattern
      phantom for axial and helical data acquisitions. Spatial resolution in DRR
      increases for thinner slice thicknesses (43% at 1.6 lp/cm for 2 mm versus 16% for
      5 mm). For the three slice thicknesses studied, the axial scanning mode provided
      better spatial resolution in DRR than helical scans performed at pitches > or =
      1.5 (41% at 1.6 lp/cm for axial, 3 mm slice versus 18% for pitch = 2), but is
      similar to helical scans with pitch of 1. The reconstruction of overlapping
      slices from helical acquisitions of pitch = 1.5 results in spatial resolution of
      the DRR that is similar to that resulting from axial scans with contiguous
      reconstruction, but also results in the fine streaks known as "zebra" artifacts
      in the DRR.

PMID- 11831577
TI  - A model for tracking concentration of chemical compounds within a tank of an
      automatic film processor.
AB  - A simple kinetic model that describes the time evolution of the chemical
      concentration of an arbitrary compound within the tank of an automatic film
      processor is presented. It provides insights into the kinetics of chemistry
      concentration inside the processor's tank; the results facilitate the tasks of
      processor tuning and quality control (QC). The model has successfully been used
      in several troubleshooting sessions of low-volume mammography processors for
      which maintaining consistent QC tracking was difficult due to fluctuations of
      bromide levels in the developer tank.

PMID- 11831578
TI  - Health politics and policy in a federal system.

PMID- 11831579
TI  - Children's Medicaid enrollment: the impacts of mandates, welfare reform, and
      policy delinking.
AB  - From 1984 to 1990. Congress enacted a series of mandates that expanded Medicaid
      eligibility for low-income children by gradually delinking Medicaid eligibility
      from welfare eligibility. The 1996 national welfare reform law nominally
      completed the delinking process when the statutory phase-in of children's
      Medicaid coverage was preserved even as the states were given increased
      flexibility for administering welfare programs. This article provides estimates
      of the impact of these fedcral policy changes on children's Medicaid enrollment
      rates and analyzes the degree of success in uncoupling children's Medicaid
      enrollment from welfare. Data from the Current Population Survey for 1979 to 1998
      are used to provide standardized enrollment probabilities for the United States
      and individual states. The results show important enrollment increases associated
      with the period of the mandated expansions, followed by enrollment declines
      associated with welfare reform. The largest increases in enrollment during this
      period were in states with historically restrictive welfare eligibility, but
      rates also rose in states that previously had relatively expansive welfare
      eligibility. The net effect was a reduction in the extent of state-to-state
      variation in enrollment. The Medicaid expansion peaked in 1995, prior to the
      advent of national welfare reform. Since then, children's Medicaid enrollment has
      fallen, with the largest declines falling on families with the very lowest
      incomes. Consistent with the desire to delink children's Medicaid coverage from
      welfare, the association between Medicaid and AFDC/TANF enrollment weakened
      during the expansionary period, but there still was a relatively strong
      relationship between policy outcomes for these two programs. Despite the policy
      changes, Medicaid coverage of children is still influenced by state-level welfare
      policy.

PMID- 11831580
TI  - The impact of Federal Alcohol and Drug Abuse block grants on state and local
      government substance abuse program expenditures: the role of federal oversight.
AB  - Are the federal Alcohol and Drug Abuse (ADA) block grant funds substituting for
      or supplementing state and local government spending on substance abuse? Using
      panel data on state and local government substance abuse programs, this study
      explores the fiscal effects of the ADA block grant money and the increased
      enforcement (after 1989) of federal restrictions on state spending of ADA block
      grants. The findings here reveal that for the current period, the federal ADA
      grant has no statistically significant effect on state and local government
      substance abuse spending both before and after 1989, and the increased
      enforcement of federal restrictions on the ADA grants after 1989 does not change
      this result. An additional finding is that lagged ADA grants have had a large
      effect on substance abuse spending both before and after 1989--a feature of the
      program not considered in previous studies.

PMID- 11831581
TI  - Effects of Tennessee Medicaid managed care on obstetrical care and birth
      outcomes.
AB  - A comparative study was conducted in two neighboring states, Tennessee and North
      Carolina, to determine whether Medicaid managed care (implemented in Tennessee as
      TennCare) affected prenatal care, care patterns at labor-delivery, and birth
      outcomes. A pre- and post-design coupled with a difference-in-difference approach
      -using North Carolina as a control--was used to assess TennCare's effects for all
      births and for three categories of high-risk mothers (under age eighteen, unwed,
      or living in high poverty areas). Data from 328,296 singleton births in birth
      files and matched birth-death files for 1993 and 1995 in both states were used to
      analyze a number of variables related to maternal behavior during pregnancy,
      utilization of care before and after labor-delivery, patterns of obstetrical care
      at delivery, and birth outcomes. Under TennCare, Tennessee mothers were
      relatively more likely to obtain no prenatal care or to wait and initiate third
      trimester care as compared to those in North Carolina. Relative utilization of
      specific prenatal procedures declined, Apgar scores fell very slightly, and birth
      abnormalities increased in the poverty subsample. TennCare had no significant
      effect on infant mortality. Utilization reductions in obstetrical services were
      achieved with apparent spillovers to non-TennCare births, but without adverse
      effects overall. TennCare was neither a panacea nor an unmitigated disaster. It
      is a model worth examining, but not uncritically.

PMID- 11831582
TI  - Harry and Louise and health care reform: romancing public opinion.
AB  - The question whether the "Harry and Louise" campaign ads, sponsored by the Health
      Insurance Association of America (HIAA) during the 1993-1994 health care reform
      debate, influenced public opinion has particular relevance today since interest
      groups are increasingly choosing commercial-style mass media campaigns to sway
      public opinion about health policy issues. Our study revisits the issue of the
      Harry and Louise campaign's influence on public opinion, comparing the ad
      campaign's messages to changes in opinion about health care reform over a twenty
      six-month period in Oklahoma. Looking at the overall trends just prior to the
      introduction of the Harry and Louise campaign, public opinion was going in the
      "wrong" direction, from the HIAA perspective. Moreover, public opinion continued
      in the wrong direction until the mid-point of the campaign. However, in either
      the turning point of the campaign in terms of message content and tone or in the
      lag period following it, public opinion reversed on each health reform issue and
      returned to pre-campaign levels. It appears from these findings that the campaign
      captured public opinion when support for issues that were unfavorable to HIAA
      members was increasing and turned public opinion back to pre-campaign levels. The
      campaign may result in many more such marriages of political interest groups and
      commercial advertisers for the purpose of demobilizing public support for health
      policy initiatives that are unfavorable to special interests.

PMID- 11831583
TI  - Impact of issue advertisements and the legacy of Harry and Louise.

PMID- 11831584
TI  - Manipulators and manipulation: public opinion in a representative democracy.

PMID- 11831585
TI  - From strategy to reality: the enactment of New York's Family Health Plus Program.

PMID- 11831586
TI  - Understanding social policy in Europe.

PMID- 11831587
TI  - Electron beam computed tomography evaluation of the rapid progression of coronary
      artery calcification in chronic hemodialysis patients.

PMID- 11831588
TI  - The current status of hepatitis C.

PMID- 11831589
TI  - Diagnostic workup of hepatitis C and the patient on maintenance dialysis.

PMID- 11831590
TI  - Insomnia is associated with systolic hypertension in uremic patients on
      hemodialysis.
AB  - A newly developed questionnaire was administered to 140 hemodialyzed patients (82
      M and 58 F) who have achieved adequate anemia correction according to the best
      guidelines with the aim: to evaluate the prevalence of clinical/subclinical
      dyssomnias in these patients; to study the influence of the dialytic shift
      (morning versus afternoon schedules) on sleep duration and disturbancies; and to
      evaluate the relationship between clinical sleep disorders and blood pressure
      values in uremic patients. Results indicated that 85% of uremic patients
      undergoing hemodialysis complain of clinical insomnia (frequent, persistent and
      associated with daytime consequences) or sub-clinical sleep disorders; patients
      dialyzing in the morning sleep significantly less during the night preceding the
      treatment, than those dialyzing in the afternoon; older patients complaining of
      clinical insomnia have a higher risk of failure to achieve target-optimal values
      in systolic blood pressure.

PMID- 11831591
TI  - The influence of different glucose concentrations in haemodialysis solutions on
      metabolism and blood pressure stability in diabetic patients.
AB  - In recent years the percentage of diabetic patients on haemodialysis has
      increased. Considering the high frequency of intradialytic hypotensive and
      hypoglycaemic episodes experienced by these patients, it was the aim of the
      present study to evaluate the influence of different dialysate glucose
      concentrations (5.5 mmol/L or 11 mmol/L) on blood pressure and glycaemic
      regulation, using special dialysis equipment - the GENIUS System. This cross
      over, prospective and randomised study, total duration 14 weeks, included 20
      diabetic patients on maintenance haemodialysis. Group 1: 9 patients dialysed
      using dialysate with a glucose concentration of 5.5 mmol/L and after 7 weeks
      switched to dialysate with a glucose concentration of 11 mmol/L. Group 2: vice
      versa. Results show a statistically higher number of patients with hypoglycaemic
      and hypotensive episodes using dialysate with a 5.5 mmol/L glucose concentration.
      Also, mean serum glucose values were higher during haemodialysis sessions with a
      glucose dialysate concentration of 11 mmol/L. There were no statistical
      differences between the groups in laboratory values, HbA1C, insulin doses or in
      anthropometric parameters. Our results suggest that fewer diabetic patients
      undergoing haemodialysis using a higher dialysate glucose concentration of 11
      mmol/L have hypoglycaemic and hypotensive episodes. Since this dialysate glucose
      concentration had no influence on lipid or hepatic metabolism, anthropometric
      parameters and especially HbA/1C values in this short-term study, the long term
      examination of its effects is warranted.

PMID- 11831592
TI  - Different types of aortic stenosis and simulation of their morphological
      hydrodynamic interdependence--in vitro study with allografts and stenotic valve
      models.
AB  - Biological valves display a dependence of valve resistance and valve area on flow
      and a phase shift between systolic flow through the valves and pressure
      difference across the valves. The pressure-flow relations of stenosed valves
      raise questions about the "best measure of stenosis". There is a need for
      quantitative evaluation of the hydrodynamic performance of homografts and
      allografts. In the present paper, we report on in vitro studies of the
      hydrodynamic behavior of homografts from human donors, allografts from different
      animal species as well as three valve models. Valve model I was designed to
      simulate flow-dependence of valve area, valve model II was designed to simulate
      restricted valve opening independent of flow, and valve model III was designed to
      simulate a flow-dependent movement of valve root in flow direction. Among other
      aspects, the effect of increased viscosity of the test fluid on the pressure
      difference and the effects of water absorption by valve tissue on valve
      characteristics were investigated. The results of the present studies clearly
      indicate that any biological valve may be modelled as a serial connection of a
      model I type valve and a model II type valve. From the results, the dependence of
      the characteristic pressure-flow relationship of a valve on valve size and valve
      distensibility can be clearly seen and the clinical significance of the
      characteristic coefficients of the pressure-flow relationship of a valve can be
      elucidated. Further, it was shown that the characteristic phase shift between
      flow and pressure difference displayed by biological valves is due to their
      movable valve plane similar to that of valve model III.

PMID- 11831593
TI  - Long term clinical and echocardiographic results of isolated aortic valve
      replacement in elderly patients.
AB  - Results after isolated aortic valve replacement with bileaflet prostheses in
      patients over 70 years old were reviewed. One-hundred-twenty-eight elderly
      patients were operated on between January 1988 and January 2000. Patients with
      associated heart disease were excluded from the study. Preoperative data, early
      and late postoperative mortality, all valve related complications and data
      concerning anticoagulation status were recorded. Hospital mortality was 9.3%.
      Mean follow-up time was 60.98 +/- 2.23 months. Twelve-year actuarial survival was
      69.6 +/- 0.08%. Valve related and anticoagulation related complication rates
      (0.8% and 1.6% respectively) and actuarial freedom (99 +/- 0.009 both) were low,
      as well as the mean interval between consecutive INR checks (18.39 +/- 1.90 days)
      and the mean INR value (2.17 +/- 0.135). Late echocardiographic results showed
      low postoperative mean transprosthetic gradients (15.48 +/- 0.94). Bileaftlet
      prostheses in the elderly can achieve excellent results with a low incidence of
      anticoagulation related complications and low risk of reoperation. Older age can
      no longer be considered a contraindication to bileaftlet prosthesis implant.

PMID- 11831594
TI  - Determination of time delay between blood and interstitial adipose tissue glucose
      concentration change by microdialysis in healthy volunteers.
AB  - For the development and use of subcutaneous glucose sensors it is important to
      know the time lag between changes in blood glucose and subcutaneous interstitial
      glucose concentration. To determine the time lag we inserted a microdialysis
      probe into the abdominal subcutaneous adipose tissue of healthy volunteers (n =
      19) and performed oral glucose tolerance tests (n = 39) over a 7-day period.
      After correction for the microdialysis system time lag, we compared the change in
      dialysate glucose concentration with the capillary blood glucose concentration.
      We found no significant delay time between a change in capillary blood glucose
      concentration and subcutaneous interstitial fluid glucose concentration using the
      Mann-Whitney test. The substantial interindividual variation of glucose recovery
      and the changing recovery in time makes it difficult to draw unambiguous
      conclusions about the exact physiological time lag. Based on the present
      experimental findings and theoretical calculations of glucose transport in
      adipose tissue, the physiological lag time is short and negligible compared to
      the system delay time of a glucose sensor.

PMID- 11831595
TI  - Ozonation of blood during extracorporeal circulation. II. Comparative analysis of
      several oxygenator-ozonators and selection of one type.
AB  - Exposure of human blood ex vivo to oxygen-ozone (O2-O3) using either dialysis
      exchangers or normal oxygenators gives rise to a number of problems, one of which
      linked to platelet activation, leads to rapid occlusion and no gas exchange.
      Semipermeable membranes were found unsuitable because, except for one, they were
      gas-transfer inefficient, allowed ultrafiltration and were more or less
      vulnerable to O3. Over the last three years we have examined several types of
      hydrophobic O3-resistant hollow fiber capillaries but, if the polypropylene
      surface is not properly coated, there is platelet aggregation and blood
      coagulation. These problems while far less relevant with O2 alone, become
      prohibitive in the presence of ozone. Recently new oxygenators have been prepared
      with special materials to make them more biocompatible and it has become possible
      to oxygenate and ozonate up to 5L of blood in about an hour, thus making the
      treatment of critical patients feasible.

PMID- 11831596
TI  - Laser technology in orthopedics: preliminary study on low power laser therapy to
      improve the bone-biomaterial interface.
AB  - Low Power Laser (LPL) seems to enhance the healing of bone defects and fractures.
      The effect of LPL in other orthopedic areas such as osteointegration of implanted
      prosthetic bone devices is still unclear. In the present study, 12 rabbits were
      used to evaluate whether Ga-Al-As (780 nm) LPL stimulation has positive effects
      on osteointegration. Hydroxyapatite (HA) cylindrical nails were drilled into both
      distal femurs of rabbits. From postoperative day 1 and for 5 consecutive days,
      the left femura of all rabbits were given LPL treatment (Laser Group-LG) with the
      following parameters: 300 Joule/cm2, 1 Watt, 300 Hertz, pulsating emission, 10
      minutes. The right femura were sham-treated (Control Group-CG). At 4 and 8 weeks
      after implantation, histologic and histomorphometric investigations evaluated
      bone-biomaterial-contact. Histomorphometry showed a higher degree of
      osteointegration at the HA-bone interface in the LG Group at 4 (p < 0.0005) and 8
      weeks (p < 0.001). These preliminary positive results seem to support the
      hypothesis that LPL treatment can be considered a good tool to enhance the bone
      implant interface in orthopedic surgery.

PMID- 11831597
TI  - Bereavement after suicide--how far have we come and where do we go from here?
AB  - This paper identifies major issues faced by the bereaved, the community, and the
      helping professions after a suicide. Some significant milestones in knowledge and
      service provision that have been achieved so far are discussed. It considers how
      past research in the fields of suicide postvention and general bereavement have
      developed new variables and frameworks with which to find a way forward in
      understanding this neglected field. The new standards of care and public policy
      are described that are anticipated in the light of these insights.

PMID- 11831598
TI  - Methodological issues in community surveys of suicide ideators and attempters.
AB  - There have been quite a number of community studies in recent years, with surveys
      being conducted among the general population, in schools, and among the elderly.
      While all of these studies have greatly contributed to our understanding of
      suicidal behavior, because of different approaches toward methodology and
      definitions, they also have some limitations. These limitations spring mainly
      from the fact that definitions of suicidal ideation and behavior vary widely
      across studies, which makes comparisons between studies unreliable. The different
      utilization of methodology is another problem that can impact the comparability
      of the community studies.

PMID- 11831599
TI  - Suicidal behavior in patients with adjustment disorders.
AB  - This retrospective study characterizes the suicidal behavior in 119 patients with
      Axis I adjustment disorders as assessed by psychiatrists at the University of
      Virginia Hospital. Results indicated that 72 patients (60.5%) had documented
      suicide attempts in the past, 96% had been suicidal during their admission to the
      hospital, and 50% had attempted suicide before their hospitalization. The most
      commonly used method of suicide attempts was overdosing. Of the sample group with
      suicide attempts in the past, 67% had Axis II diagnoses of borderline personality
      disorder and antisocial personality disorder. Adjustment disorder diagnosis in
      patients with the suicide attempts was associated with a high level of
      suicidality at admission, involuntary hospitalization and substance-abuse
      disorders. Axis II diagnoses in patients with adjustment disorders constituted
      risk factors for further suicidal behavior. Additional future prospective studies
      with reliability checks on diagnosis of adjustment disorders and suicidal
      behavior are needed.

PMID- 11831601
TI  - 2001--the international year of the volunteer.

PMID- 11831600
TI  - Sex differences in suicidal ideation in a community sample from China.
AB  - In a large sample of over 4,000 Chinese residents in the Wuling and Sino
      Vietnamese border regions of China, females had a higher incidence of ever
      wishing that they were dead. This sex difference was found regardless of marital
      status, age, and occupation.

PMID- 11831602
TI  - Re: Crisis (Vol. 22:1, 3-4).

PMID- 11831603
TI  - Training young befrienders.

PMID- 11831605
TI  - Letter across the Pacific.

PMID- 11831604
TI  - Suicidology: a victimology perspective.
AB  - In this brief essay, I have tried to show that the discipline of victimology,
      when applied to suicidal behavior, suggests new questions for researchers to
      address, including survivor surveys to identify who the survivors really are and
      what is the role of the survivor in the suicide-survivor interpersonal dynamic.

PMID- 11831606
TI  - Deliberate self-harm patients with alcohol disorders: characteristics, treatment,
      and outcome.
AB  - Deliberate self-harm (DSH) patients with alcohol problems present a considerable
      challenge for clinical services. In a study of a sample of 150 DSH patients who
      were representative of all such patients seen at a general hospital during the
      study period, 40 patients with an ICD-10 diagnosis of alcohol dependence or
      harmful use of alcohol were compared with the remainder of the sample. The
      treatment of the patients with alcohol disorders before and after the episode of
      DSH and the outcome 12-20 months later were also investigated. Compared with
      other DSH patients, those with an alcohol diagnosis were older and more often
      male, living alone, unemployed, sick, disabled, or with a past history of DSH.
      They also had higher scores on measures of anger, aggression, and impulsivity.
      Comorbid psychiatric disorder was present in 37 (92.5%) patients, this being
      depression in three-quarters of those cases. Fourteen (35.0%) patients were
      receiving treatment from the psychiatric services prior to DSH, and 33 (82.5%)
      were subsequently offered treatment. Of the patients who were followed up, 37.9%
      remained in contact with psychiatric services, 55.2% showed poor compliance with
      treatment and 44.8% reported a further episode of DSH. All patients presenting
      after DSH need to be carefully screened for alcohol disorders and for comorbid
      psychiatric diagnoses. Treatment of DSH patients with alcohol disorders should
      include the treatment of any comorbid depressive illness.

PMID- 11831607
TI  - Race and cancer genetics: lessons from BRCA1.
AB  - The effect of a patient's race or ethnicity on cancer incidence and mortality
      rates remains a neglected area of cancer research. However, with cancer
      statistics differing among various populations, research on racial and ethnic
      groups could provide clues to cancer trends. Definitions of ethnicity and/or race
      need to be established and standardizedfor use in study protocols. Accordingly,
      all research on ethnic groups must address two questions: (1) When is genetic
      research on a population appropriate? (2) How should researchers define a given
      population being studied?

PMID- 11831608
TI  - Using thalidomide in a patient with epithelioid leiomyosarcoma and Osler-Weber
      Rendu disease.

PMID- 11831609
TI  - Endoscopic ultrasound in the diagnosis and staging of pancreatic cancer.
AB  - Patients with signs and symptoms suggestive of a pancreatic neoplasm typically
      undergo initial imaging with transabdominal ultrasound or computed tomography.
      This evaluation often reveals the presence of a pancreatic mass or fullness. At
      times, the nature of the lesion is poorly characterized, with uncertainty
      remaining as to whether the lesion is an inflammatory mass or a neoplasm, and if
      it is cystic or solid. In these circumstances, endoscopic procedures such as
      endoscopic retrograde cholangiopancreatography and/or endoscopic ultrasound may
      be required. These procedures offer other means of tissue sampling, disease
      staging, and an option for palliative therapy. In this article, we review the
      role of endoscopy for the diagnosis and staging of pancreatic tumors, with a
      particular focus on endoscopic ultrasound.

PMID- 11831610
TI  - World's largest breast cancer treatment trial supports anastrozole use.

PMID- 11831611
TI  - Routine mammography screening increases except among minorities and the elderly.

PMID- 11831612
TI  - Current management of menopausal symptoms in cancer patients.
AB  - Menopause can be experienced prematurely by women with cancer and, as such, is
      often accompanied by symptoms that are becoming salient management issues. It is
      common practice to avoid estrogen replacement therapy in women with estrogen
      sensitive tumors. Therefore, the effective management of vasomotor symptoms,
      urogenital problems, and the prevention of osteoporosis and cardiac disease
      requires knowledge of nonhormonal interventions. This article discusses the
      changes women experience during menopause and the symptoms to which these changes
      can contribute. Pharmacologic options without estrogen, as well as
      nonpharmacologic interventions, are presented for the treatment of hot flashes,
      vaginal dryness, and urinary incontinence, and the maintenance of skin, bone, and
      heart health. The issue of cognitive dysfunction is also addressed. For most of
      the problems associated with menopause, viable, effective options are available
      for cancer survivors.

PMID- 11831613
TI  - Clinical trials referral resource. Current clinical trials in neuroblastoma.

PMID- 11831614
TI  - Role of adjuvant therapy in resected stage II/IIIA non-small-cell lung cancer.
AB  - The role of adjuvant therapy following complete resection of node-positive (stage
      II/IIIA) non-small-cell lung cancer remains controversial. Five-year survival
      rates in pathologic stage II disease range from 30% to 50% and in resected stage
      IIIA disease from 10% to 30%. The majority of recurrences following surgery are
      distant metastases. This two-part review, which began in the December 2001 issue,
      analyzes the role of adjuvant therapy in this setting, using an evidence-based
      approach and focusing primarily on randomized trials and meta-analyses. The key
      variables in evaluating these studies are elucidated, ranging from the extent of
      mediastinal, systemic, and "molecular" staging to the quality of the adjuvant
      treatments administered. Some of the potential flaws inherent in meta-analyses
      are reviewed. To date, there is no convincing evidence that any therapy
      consistently improves survival in the adjuvant setting. Postoperative
      radiotherapy has been associated with a significant improvement in local control,
      particularly in patients with pathologic N2 disease. Chemotherapy should be
      offered to patients on appropriate clinical trials, and active phase III trials
      are reviewed. Future strategies include novel chemotherapy, methods to reduce
      toxicity, the emerging role of neoadjuvant therapy, and the promise of new
      biologic agents.

PMID- 11831615
TI  - The present state of protein analysis and interpretation.

PMID- 11831616
TI  - From paper electrophoresis to computer-supported interpretation of capillary
      electrophoresis--clinical plasma protein analysis in Malmo, Sweden.
AB  - Protein analyses have been used in Malmo as a routine clinical diagnostic tool
      since 1953. Most serum samples are submitted for "protein profiles" including
      capillary zone electrophoresis and rate immune nephelometric quantification of
      nine proteins (five in urines), although analysis of single proteins may be
      requested. Standardization between laboratories in our region has been greatly
      improved by automation, CRM 470 calibration and external quality assurance. We
      are further extending standardization by developing computer supported
      interpretations using a program with improved user interface and graphical
      representation of electrophoretic curves superimposed upon a shaded reference
      interval. Programming is underway to provide complete automatic interpretation of
      these curves. Together, capillary electrophoresis (with access to mathematical
      analysis) and immunochemical quantifications allow a highly automated process
      accessible to further digital analysis and automated interpretation. Rapid, cost
      effective and standardized analysis of serum protein profiles should improve the
      diagnostic evaluation of many categories of patients.

PMID- 11831617
TI  - The Pavia approach to clinical protein analysis.
AB  - The protein chemistry laboratory of the Pavia University Hospital is specialized
      in the study of monoclonal components in body fluids. It is closely connected
      with the research laboratory devoted to the structural and functional study of
      pathogenic proteins and with the Clinical Chemistry Central Laboratory. The
      analyses are performed on specific medical request. The analytical approach is
      mainly based on analysis of patient's serum and urine by high-resolution agarose
      gel electrophoresis and immunofixation with the possible addition of the
      quantification of specific proteins. The interpretation of the protein pattern
      and the final reporting result from the integration of the laboratory data with
      the clinical information. This labor-intensive approach requires skills in the
      performance of protein analysis and in the interpretation/referral phase, as well
      as close communication with the attending physician.

PMID- 11831618
TI  - How the Foundation for Blood Research (FBR) has managed serum protein testing for
      New England clinicians.
AB  - Serum protein analysis has been the primary focus of the laboratories at the
      Foundation for Blood Research (FBR) since 1965. Designed by clinicians to assist
      in the diagnosis and management of their patients, the Foundation's serum protein
      analyses became tools to answer questions that were difficult or impossible to
      answer at the bedside or by traditional chemistry tests. Research on the subject
      quickly led to services that required computer assistance. Measurement of
      individual proteins expanded as need dictated and finances allowed. Serum protein
      electrophoresis was added as a necessary test early in the process. Research,
      expansion of the number of test offered, and test volumes have demanded
      automation of both testing and interpretation. Testing now includes assays of 15
      serum proteins, serum iron, and autoantibodies and is tailored to meet the needs
      of general practitioners, pediatricians, several internal medical specialties,
      and paramedical personnel. Samples rather than patients are sent to the
      laboratory and reports are returned by mail or electronic means. Physicians
      review all complex reports.

PMID- 11831619
TI  - Evidence-based laboratory interpretation system built on a large collection of
      case records with well-defined diagnoses.
AB  - A computer-based system for laboratory diagnosis was created to promote evidence
      based practice of laboratory medicine. It runs on a database consisting of 1992
      well-defined untreated cases from 38 common diagnostic categories. Clinical
      symptoms, signs, and severity were recorded together with laboratory test results
      both general and specific to the clinical diagnosis. The system has two modes in
      which to view the database: either single or multiple diagnostic categories at a
      time. In the single mode, it allows flexible filtering and quick subgrouping of
      cases within the diagnostic category by specifying parameters of interest. It is
      also capable of computing a similarity index of a case at hand to those in the
      database. The index is defined as a weighted sum of log-likelihood calculated
      dynamically from parameters chosen for the query. In the multi-mode, only the
      parameters commonly recorded in selected categories are retrieved from the
      database. The system offers a between-category comparison view of any parameter.
      The similarity indices can be also computed among categories to see how well a
      set of parameters differentiates a reference category from the others.

PMID- 11831620
TI  - A knowledge-based system to aid with the clinical interpretation of complex serum
      protein data.
AB  - In every area of science workers are finding increasing difficulty in managing
      the volume of available data. In medicine, the accelerating pace has the
      worrisome overtones of our failing to provide up-to-date care for our patients.
      In other information-intensive areas, we rely heavily on software that manages
      much of the complexity unseen. Patient care could benefit enormously from the
      incorporation of "knowledge-based" programs to aid with diagnosis and management
      of many disorders. This article describes such a system designed to organize
      complex data which can be viewed as a test cluster aimed at many disorders
      pertinent to serum proteins. This program performs complex tasks such as
      reference range adjustment, ICD-9 code assignment, and searching for diagnostic
      "signatures", to generate clinically relevant text and simple graphics. The
      results have been remarkably accurate and produce repeatable results at the rate
      of approximately 10 cases per minute. The reluctance to embrace software
      assistance in laboratory medicine may have serious consequences in the short term
      and disastrous results within a decade. Expanding the limited algorithm described
      here to include more traditional chemistry testing could provide the very
      assistance that all in clinical care desire, a laboratory tool as powerful and
      adaptable as the traditional physical exam.

PMID- 11831621
TI  - Markers of the acute phase response in cardiovascular disease: an update.
AB  - There is now widespread agreement that inflammation is a key component in the
      progression of atheromatous lesions. Inflammatory cells are present at all stages
      in the development of the atheromatous plaque, and gene knockout experiments in
      mice show that atheroma is largely prevented in the absence of the normal
      inflammatory mediators. In humans reduction of inflammation accompanies
      successful treatment strategies for atheroma. An increasing number of studies
      suggest that the acute phase protein, C-reactive protein, provides increased
      prognostic information over and above existing markers of atheroma severity or
      progression in healthy individuals and in the acute coronary syndromes. Recent
      advances in our knowledge of the normal variability of C-reactive protein levels
      and in precise and sensitive measurements strengthen the arguments for adding
      this marker to the repertoire of the routine laboratory assessment of
      cardiovascular disease.

PMID- 11831622
TI  - Protein aggregation.
AB  - Protein aggregation occurs in vivo as a result of improper folding or misfolding.
      Diverse diseases arise from protein misfolding and are now grouped under the term
      "protein conformational diseases", including most of the neurodegenerative
      disorders such as Alzheimer's disease, Parkinson's disease, the prion
      encephalopathies and Huntington's disease, as well as cystic fibrosis, sickle
      cell anemia and other less common conditions. The hallmark event in these
      diseases is a change in the secondary and/or tertiary structure of a normal,
      functional protein, leading to the formation of protein aggregates with various
      supramolecular organizations. In most cases the aggregates are organized in
      structurally well-defined fibrils forming amyloid deposits. The crucial feature
      of the amyloidogenic proteins is their structural instability induced either by
      mutations, post-translational modifications, or local conditions, such as pH,
      temperature, and co-solutes. The conformational change may promote the disease
      either by gain of a toxic activity or by the lack of biological function of the
      natively folded protein. As different molecular mechanisms are involved in the
      formation of the various forms of protein aggregates, the laboratory diagnostic
      approach remains frequently elusive.

PMID- 11831623
TI  - Protein standardization I: Protein purification procedure for the purification of
      human prealbumin, orosomucoid and transferrin as primary protein preparations.
AB  - A procedure for the purification of human prealbumin, orosomucoid and transferrin
      as primary protein preparations has been developed. The procedure describes in
      detail the chemicals, the fractionation equipment and the purification of the
      three proteins from the same starting material (a 90-donor plasma pool). The
      fractionation steps involve methods like salting out, various anion and cation
      exchange chromatographies, preparative electrophoresis, and finally, size
      chromatography. Only mild and highly reproducible fractionation methods are used
      in order to obtain high recoveries. All of these provide the best guarantee that
      no serious subfractionation has taken place. At the same time, high recoveries
      are a necessity for the pure protein to be representative of the same protein in
      vivo. The following recoveries were obtained: prealbumin 55%, orosomucoid 70% and
      transferrin 85%. The pure proteins are produced as liquid calibrators (primary
      protein preparations) dissolved in one electrolyte (0.1 mol/l KCl) and stored in
      sealed glass ampoules at -80 degrees C. These three pure proteins were used as
      primary reference preparations in the certification of the international
      reference preparation CRM 470.

PMID- 11831624
TI  - Protein standardization II: Dry mass determination procedure for the
      determination of the dry mass of a pure protein preparation.
AB  - A procedure has been developed for the determination of the dry mass of a pure
      protein preparation dissolved in one electrolyte. The procedure not only renders
      the concentration (in g/l), but additionally gives the partial specific volume of
      the protein (in ml/g). The latter is an important parameter for the
      characterization of a specific protein. Furthermore, the importance of extensive
      dialysis against one electrolyte is discussed. For the drying of human serum
      proteins it is clearly shown that KCl is preferred to NaCl due to its stable
      temperature curve. By observing the parallel fluctuations in the weight of the
      empty vials during drying, an average correction factor is introduced, which
      greatly minimizes these changes. The assay principle is discussed from a
      mathematical as well as from a practical point of view. A detailed procedure is
      described and the final results for three primary pure proteins (prealbumin,
      orosomucoid and transferrin) are presented. Finally, important parameters such as
      the wavelength of maximum absorbance, the absorption coefficient and the specific
      refractive increment are discussed and values for the three proteins are
      presented. When these parameters have been established the future determination
      of concentration and the characterization of pure protein solutions are greatly
      facilitated. These procedures were important tools for ascribing mass values for
      prealbumin, orosomucoid and transferrin to the international reference
      preparation CRM 470.

PMID- 11831625
TI  - Protein standardization III: Method optimization basic principles for
      quantitative determination of human serum proteins on automated instruments based
      on turbidimetry or nephelometry.
AB  - Quantitative protein determinations in routine laboratories are today most often
      carried out using automated instruments. However, slight variations in the assay
      principle, in the programming of the instrument or in the reagents may lead to
      different results. This has led to the prerequisite of method optimization and
      standardization. The basic principles of turbidimetry and nephelometry are
      discussed. The different reading principles are illustrated and investigated.
      Various problems are identified and a suggestion is made for an integrated, fast
      and convenient test system for the determination of a number of different
      proteins on the same instrument. An optimized test system for turbidimetry and
      nephelometry should comprise high-quality antibodies, calibrators, controls, and
      buffers and a protocol with detailed parameter settings in order to program the
      instrument correctly. A good user program takes full advantage of the optimal
      reading principles for the different instruments. This implies--for all suitable
      instruments--sample preincubation followed by real sample blanking, which
      automatically corrects for initial turbidity in the sample. Likewise it is
      recommended to measure the reagent blank, which represents any turbidity caused
      by the antibody itself. By correcting all signals with these two blank values the
      best possible signal is obtained for the specific analyte. An optimized test
      system should preferably offer a wide measuring range combined with a wide
      security range, which for the user means few re-runs and maximum security against
      antigen excess. A non-linear calibration curve based on six standards is obtained
      using a suitable mathematical fitting model, which normally is part of the
      instrument software.

PMID- 11831626
TI  - Protein standardization IV: Value transfer procedure for the assignment of serum
      protein values from a reference preparation to a target material.
AB  - A new approach for the assignment of values to serum proteins in a target
      material using a reference preparation has been developed. The procedure
      describes the general as well as the practical principles involved in the value
      assignment (with examples). Two models have been developed: 1) The direct value
      transfer between serum matrices and 2) the indirect value transfer from a pure
      protein preparation to a serum protein material. The necessary mathematical
      equations are developed and explained. The data reduction and statistical
      evaluation are discussed. The practical procedure (the transfer protocol) is
      based on six dilutions of the reference preparation assayed together with six
      dilutions of the target material. In this way imprecision is reduced and the
      proportionality of the two materials (i.e. the presence or absence of matrix
      effects) can be assessed directly by evaluating a single regression plot. If no
      matrix effects are found, the regression line will pass through zero with a slope
      equal to the ratio of the concentrations of the two materials. The transfer
      protocol is based on a multiple point value assignment obtained by several
      measurements a day repeated on several days, an important prerequisite being that
      all reconstitutions and dilutions are controlled by weighing.

PMID- 11831627
TI  - Effect of certified reference material 470 (CRM 470) on national quality
      assurance programs for serum proteins in Europe.
AB  - The introduction of the international reference material for serum proteins, CRM
      470, has resulted in significant reduction of the among-laboratory variance for
      most proteins assayed in European national quality assurance programs. In
      general, the CVs have decreased by 5 to 65%. However, both among- and within
      manufacturer variances in many cases remain unacceptably high. In addition,
      concentration-dependent differences in variance and bias are present for some
      proteins. Although some variance will persist, reducing variance and bias to
      levels required for the institution of universal reference ranges will
      necessitate more accurate transfer of values to calibrants and controls and
      improved calibration curve fitting by manufacturers, as well as better quality
      control within laboratories.

PMID- 11831628
TI  - Commutability of serum protein values: persisting bias among manufacturers using
      values assigned from the certified reference material 470 (CRM 470) in the United
      States.
AB  - Significant among-manufacturer differences in values for serum proteins persist 7
      years after the introduction of the international reference material (Certified
      Reference Material 470; Reference Preparation for Proteins in Human Serum). In
      some cases, such as transthyretin and C4, the biases actually continue to
      increase. Further efforts at standardization are needed in order to improve
      commutability of results among laboratories and are essential if universal
      reference intervals are to be developed.

PMID- 11831629
TI  - The existing interim consensus reference ranges and the future approach.
AB  - The release of the reference material for serum proteins, CRM 470/RPPHS, in 1993,
      has given rise to a great improvement in the between-laboratory variability of
      serum protein measurements worldwide. However, conversion to the new reference
      material has resulted in significant changes in reference values for some
      proteins. The establishment of new reference ranges is currently in progress; in
      the interim, several professional societies and diagnostic companies have agreed
      to use consensus reference ranges based on studies that were already undertaken.

PMID- 11831630
TI  - Using multiples of the median to normalize serum protein measurements.
AB  - Quantification of serum proteins is useful in the diagnosis and clinical
      management of many disorders. With the introduction of automated analyzers and
      standardized reference materials, one of the last barriers to more widespread
      utilization of these measurements is the lack of availability of reliable and
      transferable age- and gender-specific reference ranges. One normalization method
      that deserves consideration is converting values to multiples of the median (MoM)
      for age and gender. When two analytic methods agree, or differ only by a
      proportional amount, conversion to MoM can be used to simplify the clinical
      interpretation of serum protein results. As a test of this method, assay results
      for IgG, transferrin, and albumin from three Swedish hospitals were normalized
      using published reference ranges from the United States. All assays were
      standardized to CRM 470. IgG results were in agreement in mass units, and
      transferrin measurements were proportionally different. However, there were
      important, non-proportional differences in albumin measurements. After converting
      IgG and transferrin measurements to MoM, published reference ranges were
      appropriate for the Swedish Hospitals.

PMID- 11831632
TI  - Standardization of immunoassay for CRM-related proteins in Japan: from evaluating
      CRM 470 to setting reference intervals.
AB  - The Japan National Institute of Health (JNIH), in close collaboration with
      academic societies, commercial companies, and the Japan Society of Medical
      Technologists, has led in the attempt to standardize plasma protein assays since
      the mid 1980s. Under a framework of global standardization, they used WHO primary
      reference materials to reduce discrepancies in values reported for proteins
      assayed using different systems, thus laying the foundations for a protein
      immunoassay standardization system in Japan. With the introduction of CRM 470 in
      1993, the Japanese Committee for Clinical Laboratory Standards (JCCLS) has taken
      the initiative in promoting the use of the new material and bringing about the re
      evaluation of all systems of quality assurance in clinical laboratories. This
      eventually led to the establishment of reference intervals in Japanese
      populations of children and adults after preparation of assigned calibrators from
      CRM 470 for each assay system. Here we review the history of a series of projects
      carried out in Japan and describe several remaining problems, through which we
      will attempt to evaluate the potential value of protein immunoassay
      standardization.

PMID- 11831631
TI  - Strategy for determining racial and environmental similarities and differences
      for plasma proteins.
AB  - The aim of this protocol is to establish a common basis for the production of
      reference values and well-defined and documented reference intervals for plasma
      proteins, based on common standardization, using the IFCC/BCR/CAP Certified
      Reference Material CRM 470. The strategy is to search for racial and
      environmental/geographical similarities and sources of differences in order to
      describe the main causes for variability among smaller or larger groups in
      selected societies and to estimate the sizes of differences for the different
      proteins according to the investigated sources. For this purpose, groups of
      reference individuals are selected according to race and
      geographical/environmental location, e.g. African Americans and Caucasians from
      the US. The reference individuals are groups of approximately 160 healthy male
      blood donors, 20 to 60 years of age. Rule-out criteria are positivity for HIV,
      hepatitis B and C antibodies and blood hemoglobin below the lower reference
      limit. Exclusion in relation to different C-reactive protein (CRP) levels will be
      investigated. Coagulation, storage conditions, transport, and the procedure for
      thawing are specified. The laboratories undertaking the measurements must have
      adequate analytical performance, and calibration and quality of performance are
      defined and documented, together with recommended control materials and
      procedures. Statistical models for describing distributions and for comparing
      groups are described. It is recommended that the data be presented as reference
      limits with 90% confidence intervals of those limits.

PMID- 11831633
TI  - Soluble transferrin receptor (sTfR): biological variations and reference limits.
AB  - The aim of this study was to establish soluble serum transferrin receptor (sTfR)
      reference limits. sTfR was measured in 885 healthy subjects from 3 to 91 years
      old (433 men, 409 women), without hematological abnormalities, using an
      immunonephelometric assay. The sTfR median concentrations in our population
      decreased gradually from the group aged 3-10 years to the group aged 21-40 years,
      then there were no changes in the older groups except for the females >60 years
      of age. The interindividual variability ranged from 12.6% to 30.3% among
      different age groups, and the analytical variability was 5%. Biological factors
      and other factors associated with sTfR concentration variation were examined and
      accounted for 35% of the sTfR variability in men aged 20 years or less, and 18%
      in those older than 20 years. Also, they accounted for 45% of the variability in
      women aged 20 years or less and 14% in those older than 20 years. The main
      factors statistically associated with sTfR concentration in males were ferritin,
      orosomucoid, hemoglobin, and tobacco in all age groups and only mean corpuscular
      volume (MCV) in males less than 20 years old. In the females the main factors
      were age, orosomucoid, and hemoglobin in all age groups, MCV and tobacco in
      females less than 20 years old, and ferritin and physical activity in females
      more than 20 years old. These factors were used to define the exclusion and
      partition criteria for obtaining the reference samples. Medians for reference
      values were: 1.60 mg/l in the 3-10-year old group (males and females); 1.42 mg/l
      in males between 11 and 20 years of age, and 1.33 mg/l in females of the same
      age. In the other age groups, the median of the reference values was 1.16 mg/l,
      except in females over 60 years old, for whom it was 1.26 mg/l.

PMID- 11831634
TI  - High sensitivity C-reactive protein (CRP) reference intervals in the elderly.
AB  - High sensitivity C-reactive protein is a useful marker in clinical practice;
      however, reference intervals are not available for all age groups. Therefore, the
      aim of this study was to determine reference intervals for elderly people. The
      non-parametric reference limits were calculated for the two genders, subdivided
      into two age classes (50-64 and 65-91 years). In our selected sample population,
      we did not observe significant gender differences.

PMID- 11831635
TI  - High sensitivity immunoassays for C-reactive protein: promises and pitfalls.
AB  - C-reactive protein (CRP) has historically been measured in the clinical
      laboratory for the detection and monitoring of occult infection and inflammation,
      using immunoturbidimetric or immunonephelometric techniques. The recent
      commercial availability of automated high-sensitivity assays has enabled
      investigators to measure CRP at levels previously unattainable on a routine basis
      and to explore its clinical utility in apparently healthy individuals. CRP
      concentrations increased above the individuals' baselines but still within the
      normal reference intervals have been observed in association with increasing age,
      obesity, and smoking and in individuals with chronic infections such as Chlamydia
      pneumoniae and Helicobacter pylori. More importantly, however, data from
      prospective studies have shown CRP to be a strong and independent predictor of
      future coronary events in subjects with and without coronary heart disease. An
      algorithm for risk assessment of coronary risk employing both CRP and lipid
      concentrations has recently been proposed. However, in order for this approach to
      be incorporated into clinical practice, agreement among the various CRP methods
      must be achieved. Of critical importance to this process is a basic understanding
      of issues affecting assay performance. Factors such as assay precision,
      sensitivity, matrix effects, calibration, and standardization need to be
      addressed adequately by the in vitro diagnostic industry and the clinical
      laboratory.

PMID- 11831636
TI  - Molecular and physiologic mechanisms of drug resistance in cancer: an overview.

PMID- 11831637
TI  - Adjuvant treatment of colorectal cancer: towards tumor-specific immunotherapies.
AB  - Colorectal cancer is one of the leading causes of cancer-related mortality. After
      a series of clinical trials, the adjuvant 5-FU based chemotherapy has established
      a definitive role in the management of stage III colon cancer. The precise role
      for chemotherapy in stage II disease remains under investigation and less toxic
      treatment modalities like active specific immunotherapy have emerged as
      potentially attractive alternatives. It is most likely that the adjuvant
      treatment of colon cancer will move towards more tumor-specific immunotherapies
      using antibody- or vaccination-based strategies. Phase II/III clinical trials
      investigating these different modalities in colorectal cancer are reviewed.

PMID- 11831638
TI  - Targeting molecular signals in chk1 pathways as a new approach for overcoming
      drug resistance.
AB  - The common clinical problem in the successful treatment of cancer is the
      resistance of cancer cells to chemotherapeutic drugs. Chemotherapy kills drug
      sensitive cells, but leaves behind a higher proportion of drug-resistant cells.
      The resistance can be due to altered drug accumulation, retention, metabolism and
      distribution, or to reduced drug-target interaction. More recently, cell cycle
      progression, DNA mismatch repair (MMR) and cell death have been shown to play an
      important role in the regulation of cell resistance to anticancer drugs. Chkl
      regulation pathways, DNA MMR and p73, as well as altered apoptotic cell death
      involved in the cell resistance toward DNA damaging agents will be reviewed in
      this article.

PMID- 11831639
TI  - The challenge of pathway and environment-mediated drug resistance.
AB  - New insights into cancer biology have allowed the definition of pathways critical
      to the success of the cancer cell. These include enhanced activity of positive
      regulators of cell proliferation, including oncogenes, and loss of tumor
      suppressor gene function; inactivation of cell death or enhancement of srvival
      functions; activation of telomerase, and enhanced ability of tumor cells to
      invade and reorganize host stroma. It follows then that these pathways may also
      mediate drug resistance, in a way that is fundamentally different from
      classically defined mechanisms for drug resistance which focus on altered
      handling of the drug or the drug's target by the resistant tumor cell. It is
      expected that resistance will occur that is predicated on altered pathway
      predominance in a tumor and altered tumor microenvironment. Cases which exemplify
      this possibility are presented, including up-regulation of angiogenesis-related
      regulators in relation to inhibition of EGF-related proliferative and
      angiogenesis-promoting functions. The implications of this thinking in relation
      to development of combination regimens targeting distinct pathways are
      considered.

PMID- 11831640
TI  - Tumor physiology and drug resistance.
AB  - Clinical resistance is usually assumed to be due to the initial presence or
      selection of drug-resistant cells in tumors. While important, it is suggested in
      this review that genetically-determined causes of cellular resistance represent
      but one cause (and possibly not the major cause) of effective clinical resistance
      of solid tumors. Factors that depend on tumor physiology, and on the
      microenvironment and three-dimensional structure of solid tumors, may have a
      profound influence on their sensitivity to anti-cancer drugs. Particular emphasis
      is placed on the limited penetration of some drugs from tumor blood vessels and
      on the repopulation of tumor cells between courses of chemotherapy as causes of
      clinical resistance. Both of these mechanisms are amenable to modulation to
      improve therapeutic index. Failure to recognize that clinical drug resistance
      cannot be explained entirely by mechanisms operative at the level of the single
      cell may lead to disappointing results in clinical trials such as, for example,
      clinical failure of the strategy of reversal of multidrug resistance.

PMID- 11831641
TI  - Multidrug resistance in brain tumors: roles of the blood-brain barrier.
AB  - Malignant brain tumors and brain metastases present a formidable clinical
      challenge against which no significant advances have been made over the last
      decade. Multidrug resistance (MDR) is one of the main factors in the failure of
      chemotherapy against central nervous system tumors. The MDR1 gene encoding P
      glycoprotein (P-gp), a drug efflux pump which plays a significant role in
      modulating MDR in a wide variety of human cancers, is highly expressed in the
      blood-brain barrier (BBB). The BBB controls central nervous system exposure to
      many endogenous and exogenous substances. The exact molecular mechanisms by which
      the BBB is involved in the resistance of brain tumors to chemotherapy remain to
      be identified. The purpose of this review is to summarize reports demonstrating
      that P-gp, one of the most phenotypically important markers of the BBB, is
      present in primary brain tumors and thus plays a crucial role in their clinical
      resistance to chemotherapy.

PMID- 11831642
TI  - Malignant cells, directors of the malignant process: role of transforming growth
      factor-beta.
AB  - Malignant cells survive and thrive by expressing growth and invasion 'programs'
      that many normal cell types recognize and respond to in 'programmed' patterns. An
      early event in the molecular evolution of many malignancies loss of response to
      growth control by transforming growth factor-beta (TGF-beta) frequently due to
      mutation in the type I or type II TGF-beta receptor or a Smad protein. The
      malignant cells secrete TFG-beta that acts on the host to suppress antitumor
      immune responses, to enhance extracellular matrix production and to augment
      angiogenesis. These activities resemble those induced by TGF-beta during
      embryonic development and account in part for the 'de-differentiated' nature of
      malignant disease. Clinically, TGF-beta1 is often elevated in the plasma of
      breast cancer patients, lung cancer patients, hepatocellular carcinoma patients,
      and prostate cancer patients. Preclinically, several breast cancer models and
      prostate cancer models in vivo have demonstrated a connection between TGF-beta
      expression and increased tumorigenicity, increased invasion and drug resistance.
      In other diseases such as colon, gastric, endometrial, ovarian, and cervical
      cancers and gliomas and melanoma, loss of response to TGF-beta as a growth
      inhibitor and increased expression of TGF-beta have been associated with
      malignant conversion and progression. Elevated levels of TGF-beta are measurable
      in nude mice bearing a wide variety of human tumor xenografts; thus, these tumor
      models may serve as useful mimics of the human disease with respect to the TGF
      beta pathway. Cancer cure may be approached by blocking several of the major
      normal pathways used for tumor growth and survival in combination with cytotoxic
      therapies.

PMID- 11831643
TI  - Lineage-specific mechanism of drug and radiation resistance in melanoma mediated
      by tyrosinase-related protein 2.
AB  - A major obstacle in the clinical management of malignant melanoma is its
      intrinsic resistance to chemotherapy and radiation therapy. Consequently, most
      patients with melanoma often do not respond to conventional anticancer therapy in
      a clinically significant manner. Recent advances in cancer research have provided
      new insights into the mechanisms of intrinsic resistance in melanomas. We have
      recently reported that the over-expression of tyrosinase-related protein 2
      (TYRP2), an enzyme that is well characterized for its function in melanin
      synthesis, is associated specifically with resistance to DNA damaging drugs and
      radiation treatment. This review will summarize our findings as well as discuss
      the possible mechanisms by which TYRP2 over-expression contributes to intrinsic
      resistance in human malignant melanoma.

PMID- 11831644
TI  - Drug resistance in melanoma: mechanisms, apoptosis, and new potential therapeutic
      targets.
AB  - Melanoma is the most aggressive form of skin cancer. Patients with advanced
      disease, such as lymph node involvement and distant metastases, have 5-year
      survival rates of 50% and 10-20%, respectively. This poor prognosis largely
      results from resistance to conventional chemotherapy, namely cytotoxic drugs. The
      basis for drug resistance in melanoma is most likely dysregulation of apoptosis,
      although other mechanisms including drug transport, detoxification, and enhanced
      DNA repair may also play a role. Defects at multiple levels and in both major
      apoptotic pathways have been described in melanoma. Our laboratory has identified
      an inhibitor of apoptosis, termed survivin, that is expressed in melanoma and
      required for maintenance of melanoma cell viability. Targeting of survivin and
      other apoptotic regulators increases the sensitivity of melanoma cells to
      cytotoxic drugs, and may provide a promising new therapeutic approach to cancer.

PMID- 11831646
TI  - Mechanisms associated with cell adhesion mediated drug resistance (CAM-DR) in
      hematopoietic malignancies.
AB  - The tumor microenvironment is often overlooked when considering tumor response to
      chemotherapeutic agents. This environment consists of soluble factors, components
      of the extracellular matrix as well as cell-cell interactions. Recently, it has
      become clear that cell-cell and cell-matrix interactions result in cytoskeletal
      reorganization and the activation of multiple signal transduction pathways that
      directly influence cell survival, growth and differentiation. Experimental
      evidence shows that anti-apoptotic pathways initiated by cell adhesion are
      operative in tumor cells and, furthermore, cause resistance to mechanistically
      distinct cytotoxics. For hematopoietic tumors, cell adhesion to a single matrix,
      fibronectin is sufficient to inhibit apoptosis induced by mechanistically
      distinct cyctotoxics. Adhesion of hematopoietic tumors to this matrix blocks cell
      cycle progression, and for the human multiple myeloma 8226 cell line adhesion to
      fibronectin resulted in increased p27kip1 levels, which correlated with cell
      cycle arrest and drug resistance. A decrease in initial DNA damage induced by
      topoisomerase II inhibitors has also been observed in adherent hematopoietic
      tumor cell lines. Further studies investigating the mechanisms of cell adhesion
      mediated drug resistance may reveal novel targets directed at the reversal of de
      novo drug resistance.

PMID- 11831645
TI  - Translational regulation as a novel mechanism for the development of cellular
      drug resistance.
AB  - Cellular drug resistance is one of the principal obstacles to the clinical
      efficacy of cancer chemotherapy. In this review, we describe the potential role
      for translational regulation as a novel mechanism for modulating
      chemosensitivity. The evidence for the translational control of thymidylate
      synthase, dihydrofolate reductase, and p53 will be presented, as will
      experimental data showing how disruptions in this important regulatory process
      can lead to the rapid emergence of cellular drug resistance.

PMID- 11831648
TI  - Intermittent blood flow in solid tumours--an under-appreciated source of 'drug
      resistance'.
AB  - As the search for improved anti-cancer drugs continues, new paradigms concerning
      the reasons for clinical failures in common human solid tumours are also
      evolving. Classical drug resistance is now perhaps less often invoked to explain
      lack of treatment efficacy than are newer concepts, including 'contact
      resistance', 'tumour heterogeneity', 'regrowth resistance', and 'physiological
      barriers' to drug delivery. This commentary will explore the resistance of solid
      tumours to chemotherapy from yet another, largely ignored perspective: that of
      tumour-specific fluctuations in blood flow. Transient decreases in blood flow
      have significant implications for delivery of chemotherapeutic agents, cellular
      responsiveness to those agents, and the regrowth potential of the surviving
      tumour cells.

PMID- 11831647
TI  - Death receptor ligands, in particular TRAIL, to overcome drug resistance.
AB  - The efficacy of chemotherapeutic drugs is hampered by the occurrence of intrinsic
      and acquired drug resistance. A variety of mechanisms cause drug-resistance. A
      final common factor, however, is the reduced capacity of drug resistant cells to
      go into apoptosis following treatment with DNA damaging agents. This is due to
      defects in apoptotic pathways, for example, changes in p53. The presence of a
      common factor makes it of interest to search for ways that facilitate the cell to
      go into apoptosis following exposure to chemotherapeutic drugs. The death
      receptor ligands tumor necrosis factor (TNF), Fas ligand (FasL) and TNF-related
      apoptosis-inducing ligand (TRAIL) are able to induce apoptosis by binding to
      their cell membrane receptors. Recombinant forms of these ligands are capable to
      potentiate the effect of chemotherapeutic drugs in vitro and in vivo in the
      animal model. Based on preclinical toxicity and activity profiling, especially
      TRAIL is considered to be of interest for clinical use. Systemic treatment of non
      human primates with TRAIL did not result in acute toxicity. Animal studies
      demonstrated antitumor activity of TRAIL and potentiation of the chemotherapy
      efficacy by TRAIL. Phase 1 studies with TRAIL will therefore be initiated. As
      TRAIL is supposed to be non-toxic, it will be a major challenge to design
      surrogate end points to find the optimal dose in the clinic. In analogy to the
      herceptin therapy, it may be helpful to characterize the tumor of the patient. In
      addition, ex vivo exposure of the tumor may also be useful to select the proper
      ligand therapy for the individual patient. For optimal effect it is most likely
      that ligand therapy will be combined with chemotherapy, but even a combination of
      ligands for patient treatments can be envisioned. It is to be expected that
      smart, small molecules targeting these death receptors will be designed in order
      to lower toxicity and increase antitumor activity.

PMID- 11831649
TI  - Drug resistance in cancer: a perspective.
AB  - Drug resistance remains the thorniest obstacle in developing improved systemic
      therapies for disseminated cancer. The combination of genetic instability
      together with the great molecular heterogeneity that are displayed by malignant
      cells makes constructing effective, rational treatment programs difficult in the
      extreme. However, new insights into the action of antitumor agents at the
      molecular level plus greater understanding of the relationship of drug resistant
      states to the fundamental abnormalities that generate malignancy point the way to
      producing therapies that are more specific and therapeutically effective.
      However, a non-trival problem is the drug development system itself which is
      currently poorly set up to yield patient specific drug programs in a timely
      fashion.

PMID- 11831650
TI  - Resistance to rapamycin: a novel anticancer drug.
AB  - The macrocyclic lactone rapamycin has an established place as an immune
      suppressive agent in organ transplantation. However, more recently it has been
      recognized as an inhibitor of pathways that may be activated during malignant
      transformation and tumor progression. Thus, increasing interest is being directed
      to this class of antibiotic as potential antitumor agents. Here we summarize the
      history, mechanism of action, and mechanisms of resistance to rapamycin.

PMID- 11831652
TI  - The role for liposomal drug delivery in molecular and pharmacological strategies
      to overcome multidrug resistance.
AB  - When P-glycoprotein (PGP) was first identified as a direct mediator of multidrug
      resistance (MDR) a great deal of excitement was generated as scientists and
      clinicians anticipated the ability to successfully treat previously refractory
      cancers by blocking this drug efflux pump. More than twenty years later there is
      still minimal evidence that inhibiting PGP will have widespread impact on the
      chemosensitivity of human tumors. Yet, we know that PGP is over-expressed in many
      cancers, is associated with poor prognosis in certain tumor types and, if
      functional, will certainly reduce the accumulation of many common anticancer
      drugs inside tumor cells exhibiting elevated PGP levels. Similar situations have
      arisen more recently for other potential mediators of chemosensitivity such as
      the apoptosis antagonist protein Bcl-2. Bcl-2 has been linked to drug resistance
      and poor patient prognosis in numerous studies. There has been a great deal of
      interest in blocking expression or function of this protein to increase the
      susceptibility of tumor cells to apoptotic stimuli such as chemotherapy. However,
      preclinical and clinical evidence supporting this approach as a unilateral means
      of significantly enhancing the response of tumors to chemotherapy is limited. In
      view of these examples, it would appear likely that similar caveats will be
      experienced in the future as new molecular targets are identified for potential
      MDR reversal. Given the ever increasing evidence of genetic diversity in cancer
      development and progression, it should not be surprising that the development of
      MDR is also complex and heterogeneous. Consequently, it should also not be
      surprising that solutions to this problem are unlikely to arise from
      interventions aimed at any single resistance mechanism. These concepts suggest
      that new approaches to addressing the various molecular and pharmacological
      features associated with MDR will be necessary in order to make significant in
      roads into improving the clinical activity of current and future anticancer
      agents. This review summarizes many of the current directions being taken to
      overcome MDR and how liposomal drug delivery systems may play an important role
      in achieving this aim.

PMID- 11831651
TI  - Possible mechanisms of acquired resistance to anti-angiogenic drugs: implications
      for the use of combination therapy approaches.
AB  - The ultimate target of anti-angiogenic drugs is the genetically stable, activated
      endothelial cell of a newly forming tumor blood vessel, rather than the
      genetically unstable tumor cell population per se. This led to the notion that
      acquired resistance to such drugs may not develop as readily, if at all. While
      there is some evidence that this lack of resistance development may be the case
      for some direct-acting angiogenesis inhibitors, it is becoming apparent that
      resistance can develop over time to many types of angiogenesis inhibitors
      including, possibly, some direct inhibitors, especially when used as
      monotherapies. Possible mechanisms for such acquired or induced resistance
      include: (i) redundancy of pro-angiogenic growth factors when the drug used
      targets a single such growth factor or its cognate endothelial cell-associated
      receptor tyrosine kinase; (ii) the anti-apoptotic/pro-survival function of growth
      factors such as VEGF, which, in high local concentrations, can antagonize the pro
      apoptotic effects of various angiogenesis inhibitors; (iii) epigenetic, transient
      upregulation, or induction, of various anti-apoptotic effector molecules in host
      endothelial cells; and (iv) heterogeneous vascular dependence of tumor cell
      populations. It is suggested that long-term disease control with anti-angiogenic
      drugs can be best achieved by judicious combination therapy. In this regard, the
      great molecular diversity of anti-angiogenic drug targets, in contrast to
      chemotherapy, makes this a particularly attractive therapeutic option, especially
      when approved, commercially available drugs considered to have anti-angiogenic
      effects are used in such combination treatment strategies.

PMID- 11831653
TI  - Prospects for targeting protein kinase C isozymes in the therapy of drug
      resistant cancer--an evolving story.
AB  - The seminal discovery in 1988 that selective protein kinase C (PKC) activators
      induce multidrug resistance (MDR) in human cancer cells spawned several years of
      intensive investigations; these studies were primarily directed at the question
      of whether isozyme-selective PKC antagonism could reverse MDR phenotypes produced
      in cancer cells by P-glycoprotein and other ATP-binding cassette (ABC)
      transporters. The first section of this commentary provides a succinct overview
      of those studies. In the second section, we evaluate why the enthusiasm for
      studies of the involvement of PKC in transport-related drug resistance is
      currently diminished, and we offer an assessment of whether the PKC/MDR field
      should be revisited. The final section of the commentary highlights recent
      developments in studies of PKC targeting in experimental cancer therapeutics,
      which continues to be a vibrant field. Highlights include the sensitization of
      cancer cells to radiation- and drug-induced apoptosis by PKC inhibition.

PMID- 11831654
TI  - Perspective: evolution's struggle for existence in America's public schools.
AB  - The ongoing creation-evolution controversy in North America thrives on the
      widespread special creationist beliefs of a significant portion of the public.
      Creation science supports a literal interpretation of the Judeo-Christian Bible,
      an earth that is no more than 10.000 years old and created ex nihilo in six days
      by a monotheistic God, with no new kinds arising since the period of creation,
      and with a single flood of staggering force shaping layers of rocks and trapping
      the organisms fossilized within them. Despite decisions in numerous court cases
      that specifically exclude creationism and creation science from primary and
      secondary biology classes in America's public schools, creationists now work
      locally to minimize or remove evolution from science teaching standards. The
      nationally organized movement to resist the teaching of evolution has proven
      highly effective, influencing state and district school boards in addition to
      individual teachers and schools. Thus, if teaching about evolution and the nature
      of science is to survive in America's primary and secondary schools, scientists
      must likewise work with teachers and reach out to state and local school boards.
      In this perspective we outline the typical creationist arguments we encounter
      from students, teachers, school board members, and neighbors. We explain briefly
      how knowledge of both microevolution and macroevolution is important in medicine,
      agriculture, and biotechnology. We describe a science education controversy that
      arose within our own school district, how we responded, and what we learned from
      it. Finally, we argue that even modest outreach efforts to science teachers will
      be richly repaid.

PMID- 11831655
TI  - Parasite transmission modes and the evolution of virulence.
AB  - A mathematical model is presented that explores the relationship between
      transmission patterns and the evolution of virulence for horizontally transmitted
      parasites when only a single parasite strain can infect each host. The model is
      constructed by decomposing parasite transmission into two processes, the rate of
      contact between hosts and the probability of transmission per contact. These
      transmission rate components, as well as the total parasite mortality rate, are
      allowed to vary over the course of an infection. A general evolutionarily stable
      condition is presented that partitions the effects of virulence on parasite
      fitness into three components: fecundity benefits, mortality costs, and morbidity
      costs. This extension of previous theory allows us to explore the evolutionary
      consequences of a variety of transmission patterns. I then focus attention on a
      special case in which the parasite density remains approximately constant during
      an infection, and I demonstrate two important ways in which transmission modes
      can affect virulence evolution: by imposing different morbidity costs on the
      parasite and by altering the scheduling of parasite reproduction during an
      infection. Both are illustrated with examples, including one that examines the
      hypothesis that vector-borne parasites should be more virulent than non-vector
      borne parasites (Ewald 1994). The validity of this hypothesis depends upon the
      way in which these two effects interact, and it need not hold in general.

PMID- 11831656
TI  - Female choice via indicator traits easily evolves in the face of recombination
      and migration.
AB  - Species that exist in heterogeneous environments experience selection for
      specialization that is opposed by the homogenizing forces of migration and
      recombination. Migration tends to reduce associations between alleles and
      habitats, whereas recombination tends to break down associations among loci. The
      idea that heterogeneity should favor the evolution of isolating mechanisms has
      motivated evolutionary studies of reduced migration, habitat preference, and
      assortative mating. However, costly female choice of high-quality males can also
      evolve in heterogeneous populations and is not hindered by either recombination
      or migration. When information on male fitness is available through indicator
      traits, female choice based on these traits increases associations between female
      choice alleles and locally adapted alleles. Not only does female choice evolve in
      a heterogeneous environment, it acts to enhance the level of genetic variation
      and is thus self-reinforcing. The amount of female choice at equilibrium depends
      on how well mixed the habitats are, how much information on male genotype is
      available, and how different the habitats are. Female choice reaches the highest
      levels for intermediate levels of heterogeneity, because at such levels of
      heterogeneity there is both a high risk and high cost of mismating.

PMID- 11831657
TI  - Selection for fitness versus selection for robustness in RNA secondary structure
      folding.
AB  - I investigate the competition between two quasispecies residing on two disparate
      neutral networks. Under the assumption that the two neutral networks have
      different topologies and fitness levels, it is the mutation rate that determines
      which quasispecies will eventually be driven to extinction. For small mutation
      rates, I find that the quasispecies residing on the neutral network with the
      lower replication rate will disappear. For higher mutation rates, however, the
      faster replicating sequences may be outcompeted by the slower replicating ones if
      the connection density on the second neutral network is sufficiently high. The
      analytical results are in excellent agreement with flow-reactor simulations of
      replicating RNA sequences.

PMID- 11831658
TI  - Trade-offs between male and female reproduction associated with allozyme
      variation in phosphoglucoisomerase in an annual plant (Clarkia unguiculata:
      Onagraceae).
AB  - The genotype of an individual for allozymes such as phosphoglucoisomerase (Pgi)
      is often not neutral with regard to fitness. Studies of several taxa have found
      consistent fitness differences among Pgi genotypes expressing different
      allozymes. We conducted a greenhouse experiment with Clarkia unguiculata to
      determine whether allelic variation at the Pgi-C1 locus may affect components of
      male and female function. We found significant differences in siring success
      between pollen donors homozygous for different Pgi alleles. When a mixture of
      pollen was applied to stigmas under conditions of gametophytic competition (more
      pollen deposited on stigmas than there are ovules available to fertilize), donors
      homozygous for the C allele of Pgi sired more seeds per fruit than B-allele
      donors. Differences between genotypes with respect to female fertility per fruit
      contrasted with the male advantage associated with the C allele. Recipients
      homozygous for the C allele produced fruits with more aborted seeds and fewer
      viable seeds than recipients homozygous for the B allele. These results suggest
      that allelic variation at a single locus may have opposing effects on male and
      female reproductive success in C. unguiculata, and that trade-offs between the
      two types of reproductive success could contribute to the maintenance of
      variation at the Pgi-C1 locus.

PMID- 11831659
TI  - Fine-scale genetically based differentiation of life-history traits in the
      perennial shrub Lupinus arboreus.
AB  - Across large spatial scales, plants often exhibit genetically based
      differentiation in traits that allow adaptation to local sites. At smaller
      spatial scales, sharp boundaries between edaphic conditions also can create
      strong gradients in selection that counteract gene flow and result in local
      adaptation. Few studies, however, have examined the degree to which continuous
      populations of perennial plants exhibit genetically based differentiation in life
      history traits over small spatial scales. We quantified the degree of genetically
      based differentiation in adaptive traits among bush lupine (Lupinus arboreus)
      from nearby dune and grassland sites (sites separated by < 0.75 km) that formed
      part of a larger continuous population of L. arboreus. We also investigated the
      spatial genetic structure of bush lupine by examining how genetic structure
      differed between seeds and juvenile plants that were less than two years old. We
      calculated F-statistics from gel electrophoresis of 10 polymorphic loci. We then
      used these values to infer levels of gene flow. To examine differentiation in
      adaptive traits, we created full-sibling/half-sibling families of lupine within
      each area and established reciprocal common gardens at each site. Across two
      years, we measured canopy volume, flowering time, seed set, and mortality of
      progeny planted in each garden. Spatial genetic structure among seeds was
      virtually nonexistent (F(ST) = 0.002), suggesting that gene flow between the
      three areas could be quite high. However, genetic structure increased 20-fold
      among juvenile plants (F(ST) = 0.041). We found strong evidence for fine-scale
      genetically based differentiation and local adaptation in adaptive traits such as
      plant size, flowering phenology, fecundity, and mortality. Thus, it is likely
      that strong but differing selection regimes within each area drive spatial
      differentiation in lupine life-history traits.

PMID- 11831660
TI  - Foundations of gregariousness: a dispersal polymorphism among the planktonic
      larvae of a marine invertebrate.
AB  - Theory predicts that selection should favor genotypes that can vary their
      tendency to disperse in habitats that are spatially or temporally variable or
      those that remain near their carrying capacity. Although many marine habitats
      appear to fit these criteria, confirmed examples of dispersal polymorphism among
      marine invertebrates are exceedingly rare. Competent larvae of the gregarious
      tubeworm, Hydroides dianthus, settle specifically in response to living
      conspecific worms, but a small proportion of each spawn settle nonspecifically on
      uninhabited substrata concurrently with their gregarious siblings. Here, using a
      parental half-sib analysis, we show that the proportion of a spawn settling in
      response to uninhabited biofilm is highly heritable. When estimated as a
      continuous trait based on a one-way ANOVA, heritability is estimated to be 0.83
      +/- 0.31. When founder production was analyzed as a threshold trait, heritability
      was estimated to be 0.68 +/- 0.10 based on the breeding design experiment and
      0.65 +/- 0.09 based on the artificial selection experiments. Realized
      heritability based on the selection experiments was considerably lower, however
      (0.17 per generation and 0.02 cumulative). Artificial selection was ineffectual
      at sequentially increasing the proportion of founder larvae among inbred family
      lines, but after three generations of selection, the proportion of larvae
      settling in response to biofilm was significantly higher among inbred lines than
      among the field-collected parents. The obligate planktonic larval stage common
      among so many marine invertebrates is thought to preclude the evolution of
      dispersal polymorphisms in these animals. Theoretical expectations of variable
      dispersal may instead be realized through individual behavioral differences
      resulting in differential transport or settlement preference, but this
      possibility remains largely unexplored among marine invertebrates.

PMID- 11831661
TI  - Phylogeography and historical ecology of the North Atlantic intertidal.
AB  - Recent glaciation covered the full extent of rocky intertidal habitat along the
      coasts of New England and the Canadian Maritimes. To test whether this glaciation
      in fact caused wholesale extinction of obligate rocky intertidal invertebrates,
      and thus required a recolonization from Europe, we compared American and European
      populations using allelic diversity and techniques adapted from coalescent
      theory. Mitochondrial DNA sequences were collected from amphi-Atlantic
      populations of three cold-temperate obligate rocky intertidal species (a
      barnacle, Semibalanus balanoides, and two gastropods, Nucella lapillus and
      Littorina obtusata) and three cold-temperate habitat generalist species (a
      seastar, Asterias rubens; a mussel, Mytilus edulis, and an isopod, Idotea
      balthica). For many of these species we were able to estimate the lineage
      specific mutation rate based on trans-Arctic divergences between Pacific and
      Atlantic taxa. These data indicate that some obligate rocky intertidal taxa have
      colonized New England from European populations. However, the patterns of
      persistence in North America indicate that other life-history traits, including
      mech anisms of dispersal, may be more important for surviving dramatic
      environmental and climatic change.

PMID- 11831662
TI  - Evolution of egg target size: an analysis of selection on correlated characters.
AB  - In broadcast-spawning marine organisms, chronic sperm limitation should select
      for traits that improve chances of sperm-egg contact. One mechanism may involve
      increasing the size of the physical or chemical target for sperm. However, models
      of fertilization kinetics predict that increasing egg size can reduce net zygote
      production due to an associated decline in fecundity. An alternate method for
      increasing physical target size is through addition of energetically inexpensive
      external structures, such as the jelly coats typical of eggs in species from
      several phyla. In selection experiments on eggs of the echinoid Dendraster
      excentricus, in which sperm was used as the agent of selection, eggs with larger
      overall targets were favored in fertilization. Actual shifts in target size
      following selection matched quantitative predictions of a model that assumed
      fertilization was proportional to target size. Jelly volume and ovum volume, two
      characters that contribute to target size, were correlated both within and among
      females. A cross-sectional analysis of selection partitioned the independent
      effects of these characters on fertilization success and showed that they
      experience similar direct selection pressures. Coupled with data on relative
      organic costs of the two materials, these results suggest that, under conditions
      where fertilization is limited by egg target size, selection should favor
      investment in low-cost accessory structures and may have a relatively weak effect
      on the evolution of ovum size.

PMID- 11831663
TI  - Fertilization selection on egg and jelly-coat size in the sand dollar Dendraster
      excentricus.
AB  - Organisms with external fertilization are often sperm limited, and in echinoids,
      larger eggs have a higher probability of fertilization than smaller eggs. This
      difference is thought to be a result of the more frequent sperm-egg collisions
      experienced by larger targets. Here we report how two components of egg target
      size, the egg cell and jelly coat, contributed to fertilization success in a
      selection experiment. We used a cross-sectional analysis of correlated characters
      to estimate the selection gradients on egg and jelly-coat size in five replicate
      male pairs of the sand dollar Dendraster excentricus. Results indicated that eggs
      with larger cells and jelly coats were preferentially fertilized under sperm
      limitation in the laboratory. The selection gradients were an average of 922%
      steeper for egg than for jelly-coat size. The standardized selection gradients
      for egg and jelly-coat size were similar. Our results suggest that fertilization
      selection can act on both egg-cell and jelly-coat size but that an increase in
      egg-cell volume is much more likely to increase fertilization success than an
      equal change in jelly-coat volume. The strengths of the selection gradients were
      inversely related to the correlation of egg traits across replicate egg clutches.
      This result suggests the importance of replication in studies of selection of
      correlated characters.

PMID- 11831664
TI  - Restricted effective queen dispersal at a microgeographic scale in polygynous
      populations of the ant Formica exsecta.
AB  - Ecological constraints on effective dispersal have been suggested to be a key
      factor influencing social evolution in animal societies as well as the shift from
      single queen colonies (monogyny) to multiple queen colonies (polygyny) in ants.
      However, little is known about the effective dispersal patterns of ant queens.
      Here we investigate the microgeographic genetic structure of mitochondrial
      haplotypes in polygynous populations of the ant Formica exsecta, both between
      pastures and among nests within pastures. An analysis of molecular variance
      revealed a very high genetic differentiation (phiST = 0.72) between pastures,
      indicating that queens rarely disperse successfully between pastures, despite the
      fact that pastures were sometimes as close as 1 km. Most of the pastures
      contained only a single haplotype, and haplotypes were frequently distinct
      between nearby pastures and even between groups of nests within the same pasture.
      In the three pastures that contained several haplotypes, haplotypes were not
      randomly distributed, the genetic differentiation between nests being phiST =
      0.17, 0.52, and 0.69. This indicates that most queens are recruited within their
      parental colonies. However, a large proportion of nests contained more than one
      haplotype, demonstrating that colonies will sometimes accept foreign queens. The
      relatedness of mitochondrial genes among nestmates varied between 0.62 and 0.75
      when relatedness was measured within each pasture and ranged between 0.72 and 1.0
      when relatedness was assessed with all pastures as a reference population.
      Neighboring nests were more genetically similar than distant ones, and there was
      significant isolation by distance. This pattern may be due to new nests being
      formed by budding or by limited effective queen dispersal, probably on foot
      between neighboring nests. These results show that effective queen dispersal is
      extremely restricted even at a small geographical scale, a pattern consistent
      with the idea that ecological constraints are an important selective force
      leading to the evolution and maintenance of polygyny.

PMID- 11831665
TI  - The effects of selection for larval behavior on adult life-history features in
      Drosophila melanogaster.
AB  - Selection for late-life fecundity and longevity in adult Drosophila melanogaster
      is well known to modify numerous characteristics of life history and physiology.
      We report experiments here in which selection applied to behavior affects
      features in an identical fashion. Selection for feeding rate of larval D.
      melanogaster modifies caloric intake, as measured by the uptake and incorporation
      of labeled glucose. Selection for slow larval feeding produced lines of D.
      melanogaster in which larvae synthesized significantly less lipid prior to
      pupation and eclosed to have low early-life fecundity and a long life as adults.
      They also had greater lifetime fecundity, but lower viability of egg to hatched
      adult. Alternatively, fast-feeding larvae incorporated more lipid before pupation
      and eclosed with high early-fecundity that declined rapidly throughout their
      short adult life. Slow-feeding populations also had a significantly enhanced
      expression of the stress-resistance genes CuZn-SOD, CATALASE, and HSP70.
      Selection on larval feeding behavior reproduced the antagonistic evolutionary
      trade-off found under selection for adult life span and mimicked the
      physiological response in life span as seen in many species when dietary
      restriction is imposed on adults. Thus, nutrient acquisition during development
      appears to share a common evolutionary and genetic basis with the allocation
      processes that determine adult life-history traits and the related phenotypic
      dietary restriction phenomena.

PMID- 11831666
TI  - Evolution of the gall wasp-host plant association.
AB  - Gall wasps, or cynipids, form the second largest radiation of galling insects
      with more than 1300 described species. According to current views, the first
      cynipids were phytophagous and developed in herb stems of the Asteraceae without
      modifying plant growth or development. The first galls were supposedly
      multichambered stem swellings, and subsequent trends involved increase in gall
      complexity and reduction in the number of larval chambers. Gall wasps also have
      many of the features believed to be characteristic for phytophagous insects
      radiating in parallel with their host plants. We tested these hypotheses by
      mapping characters onto a recent estimate of higher cynipid relationships from a
      morphology-based analysis of exemplar taxa, controlling for phylogenetic
      uncertainty using bootstrapping. Characters were also mapped onto a metatree
      including all gall wasps, assembled from phylogenetic analyses as well as recent
      classifications. The results contradict many of the current hypotheses. The first
      cynipids with extant descendants were not Asteraceae stem feeders but induced
      distinct single-chambered galls in reproductive organs of herbaceous
      Papaveraceae, or possibly Lamiaceae. There has been a general trend toward more
      complex galls but the herb-stem feeders evolved from ancestors inducing distinct
      galls and their larval chambers are best understood as cryptic galls. Woody hosts
      have been colonized only three times, making the apparently irreversible
      transition from herbs to woody hosts one of the most conservative features of the
      gall wasp-host plant association. The evolution of host plant preferences is
      characterized by colonization of preexisting host-plant lineages rather than by
      parallel cladogenesis. Cynipids are mono- or oligophagous and host-plant choice
      is strongly phylogenetically conserved. Yet, the few major host shifts have
      involved remarkably distantly related plants. Many shifts have been onto plant
      species already exploited by other gall wasps, suggesting that interspecific
      parasitism among cynipids facilitates colonization of novel host plants.

PMID- 11831667
TI  - Body size variation among mainland populations of the western rattlesnake
      (Crotalus viridis).
AB  - In general, squamate reptiles follow the converse to Bergmann's rule, attaining
      smaller sizes in cooler environments, whereas other vertebrate groups follow
      Bergmann's rule, attaining larger sizes in cooler areas. Intensive studies of
      body size evolution for species of squamates are necessary to understand the
      processes responsible for this trend. Here I present data on body size variation
      among mainland populations of the western rattlesnake, Crotalus viridis. This
      species consists of two well-differentiated phylogenetic clades, therefore all
      analyses were performed for the C. viridis group as a whole and separately for
      each of the two clades within the C. viridis group. Although both phylogenetic
      and nonphylogenetic analyses were performed, the data did not show phylogenetic
      conservatism, and therefore the nonphylogenetic results are preferred. I found no
      significant relationships between mean adult female snout-vent length and any of
      the physical and climatic variables that were examined for the C. viridis group
      using simple linear regression analysis. Examined separately, I found that
      individuals of the western clade, C. oreganus, were smaller in cooler and more
      seasonal environments, whereas individuals of the eastern clade. C. viridis sensu
      stricto, were larger in cooler and more seasonal areas. Thus, the observed size
      trends were in opposite directions for the two clades. Multiple regression
      analysis revealed that seasonality was a stronger predictor of body size
      variation than was temperature for both clades. The differences in body size
      trends between these clades may be due to differences in mortality rates among
      populations.

PMID- 11831668
TI  - The evolution of sexual size dimorphism in the house finch. IV. Population
      divergence in ontogeny.
AB  - Differences among taxa in sexual size dimorphism of adults can be produced by
      changes in distinct developmental processes and thus may reflect different
      evolutionary histories. Here we examine whether divergence in sexual dimorphism
      of adults between recently established Montana and Alabama populations of the
      house finch (Carpodacus mexicanus) can be attributed to population differences in
      growth of males and females. In both populations, males and females were similar
      at hatching, but as a result of sex-specific growth attained sexual size
      dimorphism by the time of independence. Timing and extent of growth varied
      between the sexes: Females maintained maximum rates of growth for a longer time
      than males, whereas males had higher initial growth rates and achieved maximum
      growth earlier and at smaller sizes than females. Ontogeny of sexual dimorphism
      differed between populations, but in each population, sexual dimorphism in growth
      parameters and sexual dimorphism at the time of nest leaving were similar to
      sexual dimorphism of adults. Variation in growth of females contributed more to
      population divergence than did growth of males. In each population, we found
      close correspondence between patterns of sexual dimorphism in growth and
      population divergence in morphology of adults: Traits that were the most sexually
      dimorphic in growth in each population contributed the most to population
      divergence in both sexes. We suggest that sex-specific expression of phenotypic
      and genetic variation throughout the ontogeny of house finches can result in
      different responses to selection between males and females of the same age, and
      thus produce fast population divergence in the sexual size dimorphism.

PMID- 11831669
TI  - A single ancient origin of brood parasitism in African finches: implications for
      host-parasite coevolution.
AB  - Robust phylogenies for brood-parasitic birds, their hosts, and nearest nesting
      relatives provide the framework to address historical questions about host
      parasite coevolution and the origins of parasitic behavior. We tested
      phylogenetic hypotheses for the two genera of African brood-parasitic finches,
      Anomalospiza and Vidua, using mitochondrial DNA sequence data from 43 passeriform
      species. Our analyses strongly support a sister relationship between Vidua and
      Anomalospiza, leading to the conclusion that obligate brood parasitism evolved
      only once in African finches rather than twice, as has been the conventional
      view. In addition, the parasitic finches (Viduidae) are not recently derived from
      either weavers (Ploceidae) or grassfinches (Estrildidae), but represent a third
      distinct lineage. Among these three groups, the parasitic finches and estrildids,
      which includes the hosts of all 19 Vidua species, are sister taxa in all analyses
      of our full dataset. Many characters shared by Vidua and estrildids, including
      elaborate mouth markings in nestlings, unusual begging behavior, and immaculate
      white eggs, can therefore be attributed to common ancestry rather than convergent
      evolution. The host-specificity of mouth mimicry in Vidua species, however, is
      clearly the product of subsequent host-parasite coevolution. The lineage leading
      to Anomalospiza switched to parasitizing more distantly related Old World
      warblers (Sylviidae) and subsequently lost these characteristics. Substantial
      sequence divergence between Vidua and Anomalospiza indicates that the origin of
      parasitic behavior in this clade is ancient (approximately 20 million years ago),
      a striking contrast to the recent radiation of extant Vidua. We suggest that the
      parasitic finch lineage has experienced repeated cycles of host colonization,
      speciation, and extinction through their long history as brood parasites and that
      extant Vidua species represent only the latest iterations of this process. This
      dynamic process may account for a significantly faster rate of DNA sequence
      evolution in parasitic finches as compared to estrildids and other passerines.
      Our study reduces by one the tally of avian lineages in which obligate brood
      parasitism has evolved and suggests an origin of parasitism that involved
      relatively closely related species likely to accept and provide appropriate care
      to parasitic young. Given the ancient origin of parasitism in African finches,
      ancestral estrildids must have been parasitized well before the diversification
      of extant Vidua, suggesting a long history of coevolution between these lineages
      preceding more recent interactions between specific hosts and parasites.

PMID- 11831670
TI  - Cultural and genetic evolution in mountain white-crowned sparrows: song dialects
      are associated with population structure.
AB  - Bird song often varies geographically within a species; when this geographic
      variation has distinct boundaries, the shared song types are referred to as song
      dialects. How dialects are produced and their adaptive significance are
      longstanding problems in biology, with implications for the role of culture in
      the evolution and ecology of diverse organisms, including humans. Here we test
      the hypothesis that song dialect, a culturally transmitted trait, is related to
      the population genetic structure of mountain white-crowned sparrows (Zonotrichia
      leucophrys oriantha). To address this, we compared microsatellite allele
      frequencies from 18 sample sites representing eight dialect regions in the Sierra
      Nevada. Pairwise genetic distances were not significantly correlated with
      geographic distances either within or between dialects, nor did dialect groups
      form distinct genetic groups according to neighbor-joining or UPGMA analysis, and
      most variation in allele frequencies occurred among individuals rather than at
      higher levels. However, most of the remaining variation was attributable to
      differences among, rather than within, dialect regions, and this among-dialect
      component of variance was statistically significant. Moreover, when controlling
      for the effect of geographic distance, song dissimilarity and genetic distance
      between site pairs were significantly correlated. Thus, song dialects appear to
      be associated with reductions in, but not strict barriers to, gene flow among
      dialect regions.

PMID- 11831671
TI  - A comparison of phenotypic variation and covariation patterns and the role of
      phylogeny, ecology, and ontogeny during cranial evolution of new world monkeys.
AB  - Similarity of genetic and phenotypic variation patterns among populations is
      important for making quantitative inferences about past evolutionary forces
      acting to differentiate populations and for evaluating the evolution of
      relationships among traits in response to new functional and developmental
      relationships. Here, phenotypic co variance and correlation structure is compared
      among Platyrrhine Neotropical primates. Comparisons range from among species
      within a genus to the superfamily level. Matrix correlation followed by Mantel's
      test and vector correlation among responses to random natural selection vectors
      (random skewers) were used to compare correlation and variance/covariance
      matrices of 39 skull traits. Sampling errors involved in matrix estimates were
      taken into account in comparisons using matrix repeatability to set upper limits
      for each pairwise comparison. Results indicate that covariance structure is not
      strictly constant but that the amount of variance pattern divergence observed
      among taxa is generally low and not associated with taxonomic distance. Specific
      instances of divergence are identified. There is no correlation between the
      amount of divergence in covariance patterns among the 16 genera and their
      phylogenetic distance derived from a conjoint analysis of four already published
      nuclear gene datasets. In contrast, there is a significant correlation between
      phylogenetic distance and morphological distance (Mahalanobis distance among
      genus centroids). This result indicates that while the phenotypic means were
      evolving during the last 30 millions years of New World monkey evolution,
      phenotypic covariance structures of Neotropical primate skulls have remained
      relatively consistent. Neotropical primates can be divided into four major groups
      based on their feeding habits (fruit-leaves, seed-fruits, insect-fruits, and gum
      insect-fruits). Differences in phenotypic covariance structure are correlated
      with differences in feeding habits, indicating that to some extent changes in
      interrelationships among skull traits are associated with changes in feeding
      habits. Finally, common patterns and levels of morphological integration are
      found among Platyrrhine primates, suggesting that functional/developmental
      integration could be one major factor keeping covariance structure relatively
      stable during evolutionary diversification of South American monkeys.

PMID- 11831672
TI  - Estimating the unbiased estimator theta for population genetic survey data.
AB  - We consider a method of approximating Weir and Cockerham's theta, an unbiased
      estimator of genetic population structure, using values readily available from
      published studies using biased estimators (Wright's F(ST) or Nei's G(ST)). The
      estimation algorithm is shown to be useful for both model populations and real
      world avian populations. However, the correlation between Wright's F(ST) and Weir
      and Cockerham's theta is strong when compared among 39 empirical avian datasets.
      Thus, the advantage of approximating an unbiased estimator is unclear considering
      the small actual effect of theta's bias-removing power on empirical datasets.

PMID- 11831673
TI  - The probability that beneficial mutations are lost in populations with periodic
      bottlenecks.
AB  - Population bottlenecks affect the dynamics of evolution, increasing the
      probability that beneficial mutations will be lost. Recent protocols for the
      experimental study of evolution involve repeated bottlenecks-when fresh media are
      inoculated during serial transfer or when chemostat tubes are changed. Unlike
      population reductions caused by stochastic environmental factors, these
      bottlenecks occur at known, regular intervals and with a fixed dilution ratio. We
      derive the ultimate probability of extinction for a beneficial mutation in a
      periodically bottlenecked population, using both discrete and continuous
      approaches. We show that both approaches yield the same approximation for
      extinction probability. From this, we derive an approximate expression for an
      effective population size.

PMID- 11831674
TI  - Is survivorship a better fitness surrogate than fecundity?
AB  - Although fitness depends on both survivorship and fecundity, we tend to assume
      fecundity relates to fitness more directly than survivorship. In fact, several
      recent ecological studies suggest fitness depends more heavily on annual
      survivorship than annual fecundity for most taxa with lifespans longer than one
      year. These studies review elasticities of transition matrices for a broad range
      of taxa. Elasticities covary monotonically with selection gradients for
      demographic rates and are identical to selection gradients for traits rescaled to
      have mean values of zero and variance of one. For all taxa except semelparous
      perennial plants, adult survivorship has consistently higher elasticity than
      other suites of demographic rates. Fecundity only rarely has the highest
      elasticity. Thus, differences in yearly survival affect fitness
      disproportionately more than differences in yearly fecundity, even in many
      exponentially growing populations. This pattern reinforces the importance of
      interpreting the contribution of vital rates to fitness in the context of life
      history and population dynamics.

PMID- 11831675
TI  - Oviposition acceptance and fecundity schedule in the cactophilic sibling species
      Drosophila buzzatii and D. koepferae on their natural hosts.
AB  - We tested for the occurrence of oviposition acceptance for different media
      prepared with cactus tissues of three alternative cactus hosts: Opuntia
      sulphurea, O. quimilo and Trichocereus terschekii for 4 consecutive days in lines
      of two Drosophila buzzatii populations and one population of D. koepferae. Our
      results showed that the former laid significantly more eggs on both Opuntia cacti
      than on T. terschekii, whereas D. koepferae preferred T. terschekii. In addition,
      fecundity schedules differed between species: D. buzzatii laid similar numbers of
      eggs along the four-day sampling period, whereas D. koepferae showed an
      oviposition peak on the second day of egg collection on T. terschekii. We suggest
      that the between-species disparities observed in oviposition acceptance and
      fecundity schedule may be related to the temporal and spatial predictability of
      Opuntia versus T. terschekii (cardon) as part of the different adaptive
      strategies that have evolved after the split of D. koepferae and D. buzzatii from
      their recent common ancestor. Therefore, the willingness to accept hosts would be
      an important factor in the habitat selection and in the maintenance of species
      diversity.

PMID- 11831676
TI  - The rating of public health research: a complex but necessary exercise.

PMID- 11831677
TI  - Using splines to analyse latency in the Colorado Plateau uranium miners cohort.
AB  - BACKGROUND: Different approaches have been proposed to investigate latency in
      epidemiologic studies where detailed exposure histories are available. METHODS:
      We demonstrate the application of a flexible, yet parsimonious, spline function
      model to investigate latency patterns for radon progeny exposure and lung cancer
      in the Colorado Plateau uranium miners cohort. The model extends a previously
      proposed bilinear model. RESULTS: The excess relative risk (ERR) reached a
      maximum of 0.6 per 100 working level months, for exposures received 14 years
      previously. The ERR then declined, and was estimated to approach zero for
      exposures received 35 years and more in the past. The point-wise 95% confidence
      intervals supported ERRs > 0 for the period 9-32 years before the event. The
      estimated latency curve was homogeneous across categories of attained age,
      duration of exposure, rate of exposure, and smoking. CONCLUSIONS: The proposed
      spline model is a flexible tool for latency analyses, and extends previously used
      methods.

PMID- 11831678
TI  - Statistical issues of quality control in organised breast cancer screening.
AB  - BACKGROUND: European guidelines for breast-cancer screening recommend an
      integrated approach of mammography screening with subsequent assessment and
      biopsy, if required, in one screening unit under permanent quality control, for
      which target values are released. Although the calculation of the respective
      rates (e.g. for participation, assessment, biopsy, or cancer detection) appears
      trivial, the statistical assessment of their compatibility with the target values
      is less obvious. This is especially true if subjects with a positive diagnostic
      result leave the screening-assessment chain prematurely, and information about
      further diagnostic results outside the organised screening is lacking. METHOD:
      Statistical models for the basic situation, in which complete information about
      the screening and assessment outcome is available, as well as for when
      information is incomplete, are presented. The statistical methods for obtaining
      the confidence limits, statistical tests and sample sizes needed to obtain a
      desired power of tests for the process parameters of interest are also given.
      RESULTS: The sample-size calculations indicate that large numbers of enrolled
      subjects are required to obtain reasonably narrow confidence limits, and that
      incomplete information about the outcome of diagnostic procedures among screening
      positives considerably worsens the feasibility of quality control. CONCLUSIONS:
      Although the methodology is specified for breast-cancer screening, it should be
      adaptable easily to other screening issues.

PMID- 11831679
TI  - Data visualisation for time series in environmental epidemiology.
AB  - BACKGROUND: Data visualisation has become an integral part of statistical
      modelling. METHODS: We present visualisation methods for preliminary exploration
      of time-series data, and graphical diagnostic methods for modelling relationships
      between time-series data in medicine. We use exploratory graphical methods to
      better understand the relationship between a time-series reponse and a number of
      potential covariates. Graphical methods are also used to examine any remaining
      information in the residuals from these models. RESULTS: We applied exploratory
      graphical methods to a time-series data set consisting of daily counts of
      hospital admissions for asthma, and pollution and climatic variables. We provide
      an overview of the most recent and widely applicable data-visualisation methods
      for portraying and analysing epidemiological time series. DISCUSSION: Exploratory
      graphical analysis allows insight into the underlying structure of observations
      in a data set, and graphical methods for diagnostic purposes after model-fitting
      provide insight into the fitted model and its inadequacies.

PMID- 11831680
TI  - Use of longitudinal data analysis in the determination of a global score for
      total hip replacement indication in osteoarthritis patients.
AB  - BACKGROUND: A composite index would help in medical practice for considering
      total hip replacement (THR) in hip osteoarthritis. In association with other
      parameters, such as age or general status, this index could serve to objectively
      determine the time to THR surgery, and might be used as an outcome measure in
      therapeutic trials. The objective of this study was to propose such an index,
      taking into account symptomatic, structural and therapeutic variables, and impact
      on lifestyle. METHODS: A curve-fitting procedure and a marginal model were used
      to highlight the average change in the variables over time. A discrete Cox model,
      with time-dependent covariates. was then performed to study the association
      between the variables and hip surgery, leading to the construction of a composite
      index. RESULTS: The smoothing and fitting analysis suggested takes into account
      not only the variables, but also the changes in their values during the preceding
      year, when studying the association between variables and hip surgery. Five
      covariates were retained in the Cox model, among them only one concerns the
      changes during the preceding year, showing that the values of the covariates are
      more important that their changes during the preceding year for THR indication.
      The coefficients of the model were transformed into new coefficients, so that
      their sum provided a severity score with individual values 0-100. DISCUSSION:
      Based on the values of reliable variables recorded during the four last visits,
      this score can be regarded as a valid index able to objectively help with THR
      indications. This score might also be used as an outcome measure in therapeutic
      trials.

PMID- 11831681
TI  - Relative survival: comparison of regressive models and advice for the user.
AB  - BACKGROUND: Relative survival is a method of analysis of failure-time data used
      to estimate the net survival. Cancer registries frequently use this method. The
      main regressive models are the Hakulinen and Tenkanen model, and the Esteve et
      al. model, which are easily used in practice thanks to their specific software
      (SURV and RELSURV, respectively). An assessment of the behaviour of the models is
      made, with the aim of giving advice for users of lifetime data in practice.
      METHODS: Simulations were done by respecting, then violating, the basic
      hypothesis supporting the theoretical foundation of these two proportional hazard
      models (independence of the death and censor process, proportionality of risks).
      For each simulation, 100 files of either 100, 1,000, or 10,000 individuals were
      generated to assess the behaviour of the model. RESULTS: Moderate censor rates,
      with or without proportionality assumption, lead to the use of the Hakulinen and
      Tenkanen model, especially for studies with little information. Non
      proportionality of risks in the Hakulinen and Tenkanen model could be tested and
      analysed. If assumptions underlying the models are respected, the Esteve et al.
      model seems to be more precise. DISCUSSION: The choice of a model in practice
      depends on its performance, and on the user's knowledge of statistics and
      computer science. Non-proportionality of risks is common in cancer registries. In
      theory, non-proportionality of risks could be taken into account for both
      relative survival models but, for the moment, it is feasible in routine only for
      the Hakulinen and Tenkanen model. Characteristics of the software should also be
      taken into account for routine relative survival analyses.

PMID- 11831682
TI  - Lymphocyte alterations after prolonged sunlight exposure.
AB  - BACKGROUND: It has been suggested that prolonged exposure to sunlight may induce
      systemic or local immune alterations, which may facilitate the development of
      skin cancer and, perhaps, non-Hodgkin's lymphona. The effects of prolonged
      sunlight exposure on peripheral blood cells were studied. METHODS: Leukocytes and
      lymphocyte subpopulations of 12 volunteers aged 10-45 were investigated before
      and after a 3-week summer holiday in seaside resorts in Greece. Lymphocyte
      phenotypes were estimated using monoclonal antibodies and flow cytometry.
      RESULTS: There were no significant differences with respect to total numbers of T
      cells, T-helper/inducer, T-suppressor/cytotoxic, B cells or HLA-Dr+ cells.
      However, we have found evidence of lymphocyte stimulation, reflected in an
      increase in cells expressing the interleukin-2 receptor (IL-2R) and, more
      specifically, an increase in the T cells expressing IL-2R and HLA-Dr antigens. An
      increase in natural killer cells has also been noticed. CONCLUSIONS: These
      findings suggest that prolonged intense exposure to sunlight may be associated
      with immunostimulation, rather than immunosuppression.

PMID- 11831683
TI  - A tentative comparison of research activities between the Athens Department of
      Hygiene and Epidemiology and other Departments of Epidemiology in the USA and
      European community.

PMID- 11831685
TI  - Re: Breastfeeding Review 2001, 9(1): 25.

PMID- 11831684
TI  - Mother-to-mother support for women breastfeeding in unusual circumstances: a new
      method for an old model.
AB  - Support is critical for breastfeeding success. Mother-to-mother support via
      groups such as La Leche League and the Australian Breastfeeding Association,
      formerly Nursing Mothers' Association of Australia, is helpful to mothers in
      average circumstances. However, for women who are in more unusual circumstances,
      this support may be inadequate on its own. With the advent of the Internet, this
      problem has been decreased through the formation of Internet breastfeeding
      support groups. An Internet mailing list for women wishing to breastfeed their
      adopted children was used to investigate how Internet groups may provide
      breastfeeding support. Members of the mailing list were surveyed on issues
      relevant to breastfeeding support. It was identified that the mailing list
      overcame the problems of geographical isolation, lack of appropriate information
      and support and a sense of feeling alone. It is concluded that Internet
      breastfeeding support groups can provide mother-to-mother support to those
      breastfeeding in unusual circumstances. Those assisting women to breastfeed may
      refer women to these groups, use the groups as a resource in educating themselves
      or offer their knowledge and experience to such groups as a resource.

PMID- 11831686
TI  - What is normal? A study of normal breastfeeding dyads during the first sixty
      hours of life.

PMID- 11831687
TI  - Initiating breastfeeding in postwar Queensland.
AB  - The aim of this article, part of a larger study (Thorley 2000), was to determine
      and examine the practices which surrounded the initiation of breastfeeding in
      Queensland maternity hospitals in the postwar period, 1945-1965. Although it was
      assumed that mothers would breastfeed, and sound advice was available on how to
      achieve a good latch, the often arbitary delay of the first breastfeed, and
      consistently restrictive practices surrounding the frequency and duration of the
      feeds, were not conducive to an optimal start for breastfeeding. Staff shortages
      compounded the situation. Mothers felt powerless and were commonly not informed
      about whether their babies were being complemented with pooled breastmilk or
      artificial infant milk in the central nursery, nor were they asked permission for
      these to be given to their babies. Pooled breastmilk from the postnatal wards was
      available throughout this period, though in the latter part of this period there
      appears to have been an increase in the use of artificial milks.

PMID- 11831688
TI  - Community attitudes to infant feeding.
AB  - A cross-sectional study was designed to describe the social context in which
      breastfeeding occurs by examining experiences of and attitudes toward infant
      feeding within the general community. Of the 2500 randomly selected adults who
      participated in the telephone survey, 61% had been breastfed, the youngest child
      of 52% of participants (who were also parents) had been mainly breastfed but 58%
      of babies seen by participants were bottle-fed. The attitudes examined in this
      survey suggest there was little support for breastfeeding, particularly outside
      the home. Over 80% of participants agreed that bottle-feeding was more acceptable
      in public places and 70% agreed there was not always a place to breastfeed when
      outside the home. In addition, bottle-feeding was considered easier and more
      convenient indicating the social environment was not very breastfeeding friendly.
      Interventions to enhance environmental support for breastfeeding need to focus on
      reducing these barriers so that breastfeeding in public is more acceptable and
      breastfeeding in general is easier and more convenient.

PMID- 11831689
TI  - Inducing lactation: a personal account after gestational 'surrogate motherhood'
      between sisters.
AB  - In Australia in 1988, Linda Kirkman gestated a baby for her sister, Maggie
      Kirkman (conceived using Maggie's ovum and IVF). During the pregnancy, a variety
      of means were used to stimulate lactation. After the birth, several women donated
      breastmilk as supplements to Maggie's supply. The paper discusses not only the
      induction of lactation, but the cooperation of women, that enabled a baby to be
      fed breastmilk exclusively for her first four months.

PMID- 11831690
TI  - Coronavirus protein processing and RNA synthesis is inhibited by the cysteine
      proteinase inhibitor E64d.
AB  - Mouse hepatitis virus strain A59 (MHV-A59) encodes within the 22-kb gene 1 a
      large polyprotein containing three proteinase domains with proven or predicted
      cysteine catalytic residues. E64d, a specific, irreversible inhibitor of cysteine
      (thiol) proteinases, inhibits the processing of the gene 1 polyprotein.
      Specifically, E64d blocks the carboxy-terminal cleavage of p65. E64d also
      inhibits replication of MHV-A59 in murine DBT cells in a dose-dependent manner,
      resulting in reduced virus titers and viral syncytia formation. This inhibition
      of replication is associated with a rapid shutoff of new viral RNA synthesis, in
      a manner similar to that seen in the presence of cycloheximide. The E64d
      associated inhibition of RNA synthesis likely results from E64d-specific
      inhibition of processing of the gene 1 polyprotein, resulting in inactive
      proteinase or replicase proteins. These results indicate that processing of the
      MHV-A59 gene 1-encoded polyprotein is required throughout infection to sustain
      RNA synthesis and virus replication.

PMID- 11831691
TI  - Functional consequences of directed mutations in human papillomavirus E6
      proteins: abrogation of p53-mediated cell cycle arrest correlates with p53
      binding and degradation in vitro.
AB  - Clinical and epidemiological studies have implicated the involvement of human
      papillomavirus (HPV) infection in cervical tumorigenesis. We have previously
      shown that expression of high-risk (HPV16) E6 can abrogate an important cell
      cycle checkpoint mediated by p53. Sublethal DNA damage causes p53 accumulation
      and G1 arrest in normal cells, but not in cells with mutant or absent p53, or in
      cells that express HPV16-E6. To investigate the functional consequences of low
      risk (HPV11) E6 expression and to evaluate regions of E6 believed to mediate
      interaction with p53, we generated several E6 expression constructs, including
      HPV11-E6, and fourdifferent E6 mutants. HPV16E6 deltaD and HPV16E6 deltaB had
      short deletions of nucleotides encoding amino acids previously implicated in p53
      degradation and binding, respectively. HPV16E6HL and HPV11E6LH had the putative
      p53 binding domain exchanged between the high- and the low-risk types. Unlike
      HPV16-E6, HPV11-E6 and the mutant E6 proteins were not able to bind or degrade
      p53 in in vitro assays. When expressed in RKO cells, HPV11-E6 or the mutant E6
      proteins did not prevent p53 accumulation or interfere with p53-dependent
      WAF1/CIP1 mRNA expression, allowing p53-mediated G, cell cycle arrest after DNA
      damage. These findings demonstrate that low-risk and high-risk E6 proteins differ
      in their effects on p53-mediated cell cycle control and that rather subtle
      mutations of high-risk E6 can alter its ability to abrogate this important
      cellular response.

PMID- 11831692
TI  - The paramyxovirus SV5 V protein binds two atoms of zinc and is a structural
      component of virions.
AB  - The paramyxovirus simian virus 5 (SV5) cysteine-rich V protein has been shown to
      be a virus structural protein by analysis of the polypeptides of purified SV5
      virions. In addition, the V protein has been identified as a component of the
      virus nucleocapsid core both by the analysis of the polypeptides present in
      radioactively labeled preparations of purified nucleocapsids and by
      immunoelectron microscopy. Quantitative autoradiography was used to determine
      that there are approximately 350 molecules of the V protein in virions. The V
      protein has been purified from V recombinant baculovirus-infected insect cells
      and by using inductively coupled argon plasma atomic emission spectroscopy it was
      found that each molecule of V binds two zinc atoms.

PMID- 11831693
TI  - Transient gene expression of antisense RNA and coat protein-encoding sequences
      reduced accumulation of cherry leafroll virus in tobacco protoplasts.
AB  - Cherry leafroll nepovirus (CLRV) is the causative agent of blackline disease,
      which results in a fatal necrosis of the graft union of English walnut scion on
      certain rootstocks. Tobacco suspension cell protoplasts were electroporated with
      plasmid constructions, bearing or not bearing RNA-derived sequences, and,
      subsequently, were electroporated with CLRV virions or virion RNA Replication of
      CLRV in protoplasts was demonstrated by accumulation of both positive- and
      negative-sense CLRV genomic RNAs 1 and 2, capsid antigen, and virions. Three
      plasmids were tested for antiviral action. These have inserts that were derived
      from the coat protein gene, inserted in both orientations, and from the 3'
      terminal sequence that is nearly identical in RNA 1 and RNA 2, oriented for
      expression of antisense RNA. Plasmids were introduced into protoplasts 12 hr
      prior to introducing the virions or virion RNA. CLRV accumulation was reduced
      significantly by prior electroporation of plasmids intended to express coat
      protein or 3' antisense RNA, but not by electroporation of plasmid without insert
      or plasmid with coat protein encoding sequences in the antisense orientation.
      These results demonstrate the utility of transient expression in a protoplast
      system for comparing the efficacy of a variety of virus-derived and other
      sequences for their potential application in virus control strategies.

PMID- 11831694
TI  - Expression and purification of glutathione S-transferase-tagged HIV-1 gp120: no
      evidence of an interaction with CD26.
AB  - We describe the use of a new baculovirus expression vector to enable the
      secretion of the major surface glycoprotein of HIV-1 (gp120) fused to the carboxy
      terminus of the widely used affinity tag glutathione S-transferase. The secreted
      protein can be purified in a single step with the minimum of denaturation on
      immobilised glutathione and is as active as the parental molecule in binding CD4.
      We use this molecule in a variety of assay formats to examine the gp120
      interaction with CD26, a reported auxiliary molecule in the HIV entry process. We
      find no evidence of a CD26-gp120 interaction in the absence or presence of CD4.

PMID- 11831695
TI  - Characterization of a functional hepatocyte nuclear factor 3 binding site in the
      hepatitis B virus nucleocapsid promoter.
AB  - Mutational analysis of the hepatitis B virus (HBV) nucleocapsid promoter
      previously demonstrated that a regulatory sequence element (CpE) located between 
      72 and -56 modulated the level of transcription from this promoter in
      differentiated, but not dedifferentiated, hepatoma cell lines. Using gel
      retardation analysis, it was shown that the formation of a complex between the
      nucleocapsid CpE promoter sequence and the DNA-binding proteins present in the
      differentiated hepatoma cell line Huh7 was inhibited from forming in the presence
      of either the large surface antigen promoter hepatocyte nuclear factor 3 (HNF3)
      binding site or an HNF3beta-specific antiserum. Purified recombinant HNF3alpha
      transcription factor was also shown to bind specifically to the CpE promoter
      sequence by gel retardation and DNase I footprinting analysis. In addition, DNase
      I footprinting analysis supported the suggestion that the nucleocapsid promoter
      region contains a second HNF3 binding site located between -112 and -86. The
      nucleocapsid promoter CpE regulatory element was shown to be a functional HNF3
      binding site capable of mediating HNF3beta-specific transcriptional
      transactivation in transient transfection analysis. These results suggest that
      the liver-enriched family of HNF3 transcription factors is involved in regulating
      the level of expression from the nucleocapsid promoter, in addition to the large
      surface antigen promoter, and is likely to be important in the coordinate
      regulation of HBV transcription during infection.

PMID- 11831696
TI  - Cytotoxic T lymphocyte escape variants, induced mutations, and synthetic peptides
      define a dominant H-2Kb-restricted determinant in simian virus 40 tumor antigen.
AB  - Immunization of C57BL/6 mice with syngeneic cells transformed by simian virus 40
      large T antigen (SV40 T ag) induces the generation of T antigen-specific
      cytotoxic T lymphocytes (CTL) which are restricted by the major
      histocompatibility class I antigens H-2Db and H-2Kb. Previous studies have shown
      that the H-2Db-restricted CTL response is directed to at least three distinct
      epitopes (I, II/III, and V) in the SV40 T antigen which have been precisely
      mapped using deletion mutagenesis and overlapping synthetic peptides. Although in
      vivo the CTL response to SV40 T antigen is dominated by the H-2Kb class I
      antigen, the precise location of the H-2Kb-restricted epitope(s) was not known,
      and whether there was multiplicity of H-2Kb-restricted epitopes remained unclear.
      In this study, we have defined the minimal recognition epitope for the SV40
      specific H-2Kb-restricted CTL clone Y-4 as T antigen residues 404-411 by using T
      antigen deletion and point mutants and synthetic peptides. DNA sequence analysis
      of the region encoding residues 404-411 from the T antigens expressed in three
      independently isolated CTL clone Y-4 escape variants identified inactivating
      mutations capable of abrogating CTL recognition. Estimation of CTL precursor
      (CTLp) frequencies by limiting dilution analysis revealed that CTLp specific for
      epitope IV represent a large percentage of the total CTL response elicited by the
      intact T antigen in H-2b mice. Immunization of B6 mice with cells expressing a T
      antigen derivative deleted of residues 404-411 revealed that site IV represents
      the only immunodominant H-2Kb-restricted epitope within T antigen.

PMID- 11831697
TI  - Identification of a CD4+ T cell epitope within the M protein of a neurotropic
      coronavirus.
AB  - A significant CD4+ T cell response against the transmembrane (M) protein can be
      detected in the spleens of C57Bl/6 mice infected intraperitoneally with a
      sublethal injection of the neurotropic JHM strain of mouse hepatitis virus (MHV
      JHM), but not in those of mice with the chronic demyelinating encephalomyelitis
      caused by this virus. With the ultimate goal of determining the role of the M
      specific response in the pathogenesis of MHV-JHM-induced neurological diseases,
      CD4+ T cell epitopes within the M protein were identified using vaccinia virus
      recombinants expressing truncated forms of the protein and peptides spanning most
      of the M protein in cell proliferation assays. Peptides covering residues 128-147
      contain at least one CD4+ T cell epitope for MHV-JHM. Within this region is a
      sequence (residues 135-143) which matches the recently described MHC class II I
      Ab binding motif. Delineation of this epitope should facilitate analysis of the
      role of the M-specific CD4+ T cell response in the development of acute and
      chronic neurological infections caused by MHV-JHM.

PMID- 11831698
TI  - Expression of the complementary-strand transcripts from BamHI-A region of the
      Epstein-Barr virus genome in various induced virus-carrying B cell lines.
AB  - The complementary-strand transcripts from Epstein-Barr virus BamHI-A-I fragments
      (also called the BARF0 RNAs) were first found in a nasopharyngeal carcinoma
      passaged in nude mice, c15, and soon proved to exist in various EBV-associated
      tumors and virus-carrying B cell lines. The data from previous studies revealed
      that the BARF0 transcripts have a highly spliced structure, whereas the evidence
      about their in vivo translational products remains few. The BARF0 RNA is also
      somehow considered as a new member of the viral latent transcripts. In order to
      know further about its transcriptional profile, we investigated its transcription
      in several EBV-carrying B cell lines during different viral stages. Our results
      show that (1) at least some of the BARF0 transcripts are transcribed during the
      viral lytic stage in the tested inducible lines; (2) the major lytic BARF0 mRNA
      appears heterogeneous in size (2.5 to 4.2 kb) among different lines; (3) in P3HR1
      and Akata lines, the major BARF0 transcript is highly spliced and sensitive to
      both an inhibitor of the viral DNA polymerase and of protein synthesis. The
      identification of such lytic BARF0 RNAs may help us to understand further about
      their complex gene expression.

PMID- 11831699
TI  - Identification of a satellite double-stranded RNA in the parasitic protozoan
      Trichomonas vaginalis infected with T. vaginalis virus T1.
AB  - Co-infection by a 0.5-kb small double-stranded (ds) RNA together with Trichomonas
      vaginalis virus (TVV) genomic 4.6-kb dsRNA is commonly observed in a number of T.
      vaginalis isolates. By molecular cloning and primer extension experiments, the
      497-bp cDNA sequence of a 0.5-kb dsRNA co-infecting with TVV-T1 in T vagina/is T1
      isolate was elucidated. Consistent with the replication cycle of a typical dsRNA
      virus, a plus-strand viral RNA beginning at +1 of the 0.5-kb dsRNA was identified
      in infected T. vaginalis T1 cells by primer extension and Northern hybridization
      studies. The 0.5-kb dsRNA was separately encased in TVV capsids from the viral
      genomic dsRNA, as shown by protein analysis and electron microscopic examination
      of viral particles purified by multiple rounds of CsCl gradient centrifugation.
      The riboprobes transcribed from a cloned cDNA of the 0.5-kb dsRNA exhibited
      strong hybridization to a small dsRNA in a T vaginalis T9 isolate, which harbors
      a TVV-T9 distantly related to TVV-T1, but the same probes showed very little
      hybridization to the viral genomic dsRNA of both TVV-T1 and TVV-T9. Very little
      sequence homology between the 0.5-kb dsRNA and the 4.6-kb dsRNA in TVV-T1 was
      found by computer-assisted analysis, suggesting that the small dsRNA in T.
      vaginalis T1 is not derived from the genome of TVV-T1 or other distantly related
      T. vaginalis viruses. These results suggest that the small dsRNAs in T vaginalis
      are satellite RNAs of T. vaginalis virus.

PMID- 11831700
TI  - Protein-primed RNA synthesis in vitro by the virion-associated RNA polymerase of
      infectious pancreatic necrosis virus.
AB  - The 94-kDa virion-associated RNA-dependent RNA polymerase (RdRp) is present in
      infectious pancreatic necrosis virus in two forms: (i) as a free polypeptide
      (VP1) and (ii) as a genome linked protein (VPg) (J. G. Calvert et al., 1991, J.
      Gen. Virol. 72, 2563-2567). VP1 was guanylylated in vitro by incubating purified
      virus in the presence of [alpha2P]GTP. During further incubation in an in vitro
      RNA polymerase reaction mixture (in the presence of unlabeled GTP), the
      radiolabeled VP1-pG complex was "chased" via nascent RNA strands and replicative
      intermediates to a VP1-dsRNA complex. Labeled VP1-pG was recovered from the
      intermediate as well as from the final reaction products by digestion with RNase
      A and RNase V1, a dsRNA-specific nuclease. Analysis of the reaction products
      indicated that only the plus strands of the two genome segments were being
      synthesized in vitro which remained base-paired to their templates. The results
      suggest that in vitro transcription by the virion RdRp is primed by VP1 and then
      proceeds via an asymmetric, semiconservative, strand-displacement mechanism.

PMID- 11831701
TI  - Stimulation of the human cytomegalovirus IE enhancer/promoter in HL-60 cells by
      TNFalpha is mediated via induction of NF-kappaB.
AB  - TNFalpha enhances the basal activity of the major Immediate Early (IE)
      enhancer/promoter of human cytomegalovirus (HCMV) in the immature premonocytic HL
      60 cell line. The stimulatory effect of TNFalpha is mediated by induction of the
      transcription factor NF-kappaB, which specifically binds to the 18-bp repetitive
      sequence motif of the enhancer region. Complex formation could be competed by
      oligonucleotides representing the 18-bp sequence motif or the prototype NF-kappaB
      sequence of the immunoglobulin kappa gene. In gel mobility shift assays antisera
      specific to NF-kappaB p50 and p65 subunits were shown to react with the DNA
      protein complex. Addition of the antioxidant PDTC blocked TNFalpha-mediated
      stimulation in a dose dependent manner. Electrophoretic mobility shift assays
      indicated that PDTC prevents NF-kappaB induction. Furthermore, it is suggested
      that protein kinases like PK-C are involved in the TNFalpha signal transduction
      pathway which leads to the activation of NF-kappaB and its binding to the HCMV IE
      enhancer in HL-60 cells. Our data are consistent with a role of TNFalpha in
      reactivation of latent HCMV infection in premonocytic cells.

PMID- 11831702
TI  - Analysis of the proteolytic processing and activation of the rice tungro
      bacilliform virus reverse transcriptase.
AB  - Rice tungro bacilliform virus (RTBV) is a plant pararetrovirus and member of the
      badnavirus subgroup. Open reading frame (ORF) 3 encodes the viral capsid protein,
      protease (PR), and reverse transcriptase (RT). A DNA fragment of ORF 3 that
      contains PR and RT sequences was previously expressed in insect cells to produce
      the PR/RT polyprotein that was processed to yield p62 and p55. p62 and p55 share
      common N-terminal amino acid sequences and exhibit reverse transcriptase
      activity. Mass spectrometry was employed to determine the precise molecular
      weight of the p62 and p55 proteins and enabled determination of the C-termini for
      both proteins. ORFs encoding either p62 or p55 were constructed and expressed in
      insect cells using the baculoviruses 62R-BBac and 55R-BBac, respectively. The
      recombinant p62R and p55R proteins were purified separately and shown to have the
      same enzymatic activities as previously reported for the processed p62 and p55.
      The putative active site of the PR was mutated (mpr), and the resulting mpr/RT
      ORF was expressed in insect cells using the baculovirus mpr/RT-BBac. The mpr/RT
      polyprotein was not processed in insect cells, resulting in the accumulation of
      the approximately 87-kDa mpr/RT polyprotein. This study further extends the
      understanding of p62 and p55 and clarifies the role of the RTBV PR in processing
      of the RT.

PMID- 11831703
TI  - Translation of the second gene of peanut clump virus RNA 2 occurs by leaky
      scanning in vitro.
AB  - The two 5'-proximal open reading frames of peanut clump virus RNA 2, which encode
      the coat protein of 23 kDa and a protein of 39 kDa (P39), are both translated in
      vitro from genomic RNA 2. We have studied the translational strategy involved in
      the initiation at the second AUG of RNA 2, which is the initiation codon of P39.
      Mutation experiments with synthetic transcripts corresponding to the 5'-half of
      RNA 2 ruled out mechanisms of P39 translation initiation involving termination
      reinitiation and internal ribosomes entry. The results were consistent, however,
      with a leaky scanning mechanism for P39 initiation, in which about one-third of
      the ribosomes fail to initiate translation of coat protein and scan along the
      template to initiate translation at the AUG of the P39 gene, more than 1000
      residues in from the 5'-terminus of the RNA 2.

PMID- 11831704
TI  - A 20,500-Dalton protein is coded by region E3 of subgroup B but not subgroup C
      human adenoviruses.
AB  - There is an open reading frame (ORF) between ATG2089 and TGA2656 in the early E3
      transcription unit of subgroup B adenovirus 3 (Ad3) that could encode a protein
      of 20,500 MW (20.5K). This ORF also exists in Ad7, Ad11, and Ad35 (subgroup B).
      An antipeptide antiserum made in rabbits against the predicted Ad3/7 20.5K
      protein immunoprecipitated two diffuse bands with apparent molecular weights of
      about 22K and 36K from Ad3- or Ad7-infected cells. These bands were also detected
      in immunoblots. These bands were not seen in mock-infected cells or cells
      infected with Ad3 or Ad7 mutants that delete the gene for 20.5K. In vitro
      transcription and translation of the 20.5K gene yielded a protein of about 18K,
      suggesting that this may be the primary translation product and that the 22K and
      36K forms of 20.5K arise by post-translation processing. Pulse/chase experiments
      suggest that the half-life of the 22K form is short, and that this form is
      further modified to the 36K species. In accord with these results and as judged
      by its predicted sequence, 20.5K appears to be a membrane glycoprotein with a
      potential N-terminal signal sequence, a second hydrophobic putative transmembrane
      domain, and two potential Asn-linked glycosylation sites. The 20.5K protein was
      synthesized throughout the course of the infection. Ad3 and Ad7 mutants lacking
      20.5K grew as well as wild-type Ad3 and Ad7, indicating that, in common with
      subgroup C E3 proteins, the 20.5K protein is dispensable for virus replication in
      cultured cells. The 20.5K gene is totally absent from the E3 region of Ad2 and
      Ad5 (subgroup C). The gene is also absent or highly diverged in the E3 region of
      Ad12 (subgroup A) and Ad40 (subgroup F). Given that E3 genes may counteract host
      defenses, the 20.5K protein may contribute to the unique pathogenic properties of
      subgroup B human adenoviruses.

PMID- 11831705
TI  - Improved retroviral packaging lines derived from spleen necrosis virus.
AB  - Using highly efficient gene expression vectors, we constructed new retroviral
      packaging lines derived from spleen necrosis virus. Core proteins are expressed
      from the murine leukemia virus promoter and enhancer followed by the tripartite
      leader sequence of an adenovirus. Using different plasmids for envelope
      expression, we found that the efficiency of vector transduction is dependent on
      the level of gag-pol expression. The level of envelope expression did not have a
      measurable impact on vector virus titers. The new helper cell lines do not
      contain any sequences homologous to vector genomes. They transduce standard
      retrovirus vectors with titers up to 10(6) colony forming units per milliliter of
      supernatant tissue culture medium. No replication-competent virus was observed.

PMID- 11831706
TI  - Self-limiting, cell type-dependent replication of an integrase-defective human
      immunodeficiency virus type 1 in human primary macrophages but not T lymphocytes.
AB  - Integration of retroviral DNA into the host cell genome, catalyzed by the
      integrase (IN) protein, is thought to be required for replication. We show here
      that one IN-minus defective mutant of human immunodeficiency virus type 1 (HIV-1)
      is able to replicate in macrophages but not in peripheral blood lymphocytes
      (PBLs). Replication of the HIV-1 defective mutant, however, was inefficient and
      self-limiting. The absence of integration in the HIV-1 IN mutant in contrast to
      the wild-type implies that the replication of the IN mutant depends on the
      transcription of the extrachromosomal forms of viral DNA. In both PBLs and
      macrophages circular forms of DNA were detected at significant levels, indicating
      that the lack of a complete functional IN protein does not preclude nuclear
      import of HIV-1 DNA. Cell-associated p24 was absent in the IN-defective-infected
      PBLs, suggesting a transcriptional block of the extrachromosomal forms of HIV-1.
      These results show the existence of different strategies for HIV-1 replication
      depending upon the cell type, and indicate the necessity of integration of viral
      DNA for the self-maintained progression of the infection.

PMID- 11831707
TI  - Analysis of the complete nucleotide sequence of African swine fever virus.
AB  - We present an analysis of the complete genome of African swine fever virus (ASFV)
      strain BA71V, including 80 kbp of novel sequence and 90 kbp previously reported
      by several authors. The viral DNA is 170,101 nucleotides long and contains 151
      open reading frames. Structural and/or functional information is available on 113
      viral proteins. ASFV encodes five multigene families, putative membrane and
      secreted proteins, and enzymes involved in nucleotide and nucleic acid metabolism
      (including DNA repair) and protein modification. Database comparisons have
      provided clues about genes that may modulate the virus-host interaction, thus,
      possibly controlling ASFV virulence and persistence. The virus possesses genes
      similar to CD2, IkappaB, C-type lectins, MyD116/gadd34/gamma, 34.5, bcl-2/bax,
      iap, NifS, and ERV1, which may allow a viral regulation of cell adhesion,
      apoptosis, and redox metabolism, as well as of the host immune response against
      ASFV infection. The proteins encoded by different ASFV isolates are highly
      similar, the most variable ones being those belonging to multigene families, some
      membrane proteins, and those containing tandem repeats. DNA sequence data confirm
      the intermediate characteristics of ASFV between poxviruses and iridoviruses,
      supporting the notion that ASFV belongs to an independent virus family.

PMID- 11831708
TI  - Domains in middle-T antigen that cooperate in polyomavirus-mediated oncogenic
      transformation.
AB  - Middle-T antigen is the oncogenic protein of Polyomavirus and associates with
      several cellular enzymes involved in signal transduction, e.g., Src tyrosine
      kinases, phosphatidylinositol 3-kinase (PI 3-kinase), protein phosphatase 2A
      (PP2A), and Shc, an SH2 domain-containing adapter protein. We have shown earlier
      that middle-T is a target of a cell cycle-regulated serine/threonine-specific
      kinase, presumably p34cdc2. Phosphorylation of middle-T by p34cdc2 results in
      increased apparent M, weight of the protein on SDS-polyacrylamide gels. Two
      threonine residues in positions 160 and 291, respectively, were identified in the
      middle-T sequence as putative targets of a cyclin-dependent kinase. Replacement
      of threonine 160 by alanine resulted in a transformation-defective mutant protein
      that was still capable of forming all the complexes with cellular proteins,
      suggesting that additional characteristics of middle-T are required for cell
      transformation. In the present study we report that the defect of the T160A
      middle-T mutant is compensated by mutations introduced into a domain encompassing
      amino acids 253 to 302. In particular, mutating serine 283, a canonical
      phosphorylation site for a cyclin-dependent kinase, to an alanine residue
      rendered the T160A middle-T mutant wild type. Based on these results we suggest
      that cell cycle-specific phosphorylation of specific serine and threonine
      residues by cyclin-dependent kinases regulates middle-T function.

PMID- 11831709
TI  - Biosynthesis and localization of the Autographa californica nuclear polyhedrosis
      virus 25K gene product.
AB  - Mutations of the AcMNPV 25K gene are associated with the "few polyhedra"
      phenotype (M. J. Fraser et al., 1983, J. Virol. 47, 287-300; B. Beames and M. D.
      Summers, 1989, Virology 168, 344-353). Polyclonal antisera was produced and used
      to investigate the time course of expression and localization of the 25K protein
      in infected cells. Western blot analysis detected 25K protein in both cytosolic
      and nuclear extracts from 18-24 hr p.i. through 96 hr p.i. and also in purified
      viral occlusions, but not in purified virions. Immunogold electron microscopy
      revealed that 25K protein was predominantly associated with amorphous cytoplasmic
      structures and to a lesser extent with a more electron-dense structure in the
      nucleus. Viral occlusions in cell sections were not specifically labeled by 25K
      antibody. Observations of purified viral occlusions and nuclei prepared for
      immunogold EM revealed the presence of contaminating amorphous material that was
      labeled with 25K antibody.

PMID- 11831710
TI  - Acylation of the Marburg virus glycoprotein.
AB  - The surface protein of Marburg virus (GP) is modified by acylation, as shown by
      labeling with [3H]myristic and [3H]palmitic acid. Acylation of GP also occurred
      when it was expressed in insect cells with the baculovirus expression system. Gas
      chromatographic analyses of the bound fatty acids indicated that exogenously
      added [3H]myristic acid was partly metabolized to palmitic and stearic acid. To
      elucidate the nature of the fatty acid bond, [3H]palmitic acid-labeled GP was
      treated with mercaptoethanol. Since the fatty acids were removed by this
      treatment, it is concluded that the linkage is of the thioester type. A putative
      attachment site for thioester-linked fatty acids consisting of two cysteine
      residues located between the transmembrane anchor and the carboxy-terminal
      cytoplasmic tail of GP (Cys671 and Cys673) could be identified. Site-directed
      mutagenesis of these two amino acids to alanine residues clearly demonstrated
      that both cysteines could serve as acylation sites.

PMID- 11831711
TI  - Tumor regression is associated with a specific immune response to the E2 protein
      of cottontail rabbit papillomavirus.
AB  - Cottontail rabbit papillomavirus is the major papillomavirus animal model with
      which to study host-virus interactions. As with human papillomaviruses,
      papillomas may spontaneously regress, persist, or progress to carcinoma. Here we
      show that the majority (88%) of regressor rabbits had antibody to the
      nonstructural protein E2 compared to 29% in animals with persisting papilloma.
      The antibody response to other nonstructural viral proteins was the same for
      rabbits with regressing and persisting papilloma. The cellular immune response
      was measured by an in vitro proliferation assay. The responses to E6 and E7 were
      infrequent and similar in papilloma-bearing and in regressor rabbits and no
      rabbits responded to E1. In contrast, the response to E2 was more frequent in
      regressor rabbits. These data suggest that E2-specific immune responses may play
      a role in tumor regression.

PMID- 11831712
TI  - Bent DNA in the large intergenic region of wheat dwarf geminivirus.
AB  - Wheat dwarf virus (WDV) is a member of the geminivirus group, unique plant DNA
      viruses which replicate exclusively via dsDNA replication intermediates. The
      large intergenic region (LIR), a nontranscribed regulatory region, contains an
      inverted repeat with the potential to form a stem-loop structure in which the
      initiation site for WDV (+)strand (virion-sense) DNA replication has been mapped.
      In this work, we have studied by two-dimensional electrophoresis and by electron
      microscopy the DNA structure of the WDV LIR and we have identified a DNA sequence
      which confers a static DNA curvature. This is the first report of the occurrence
      of DNA bending in the regulatory region of a geminivirus genome. The bending
      locus, defined by an 80-bp cluster of A(T) tracts, is located downstream from the
      potential stem-loop. The A(T) tract proximal to the stem-loop structure is
      separated by 14 bp from the inverted repeat, and deletion of distal A(T) tracts
      abolished the curvature of the new WDV deltaLIR. The bending center maps
      approximately 80 bp downstream from the putative initiation site for (+)strand
      DNA replication and approximately 70 bp upstream from the TATA box for virion
      sense transcription. The possible implications of the DNA bending locus as a
      regulatory element of WDV DNA replication and/or virion-sense transcription are
      discussed.

PMID- 11831713
TI  - Translation efficiency of the human T-cell leukemia virus (HTLV-2) gag gene
      modulates the frequency of ribosomal frameshifting.
AB  - The regulation of ribosomal frameshifting during translation of the polycistronic
      mRNA of human T-cell leukemia virus (HTLV) was studied in a cell-free system.
      Translation inhibitors such as cycloheximide and puromycin antibiotics were much
      more effective in blocking the synthesis of the frameshift polypeptide Gag-Pro
      than the synthesis of the Gag product. The preferential inhibition of the
      frameshift polypeptide Gag-Pro by the two antibiotics was not a reflection of the
      different sizes of the two gene products, but rather a consequence of the effect
      of the inhibitors on ribosomal translation efficiencies. To further analyze the
      effect of translation efficiencies on ribosomal frameshifting, we compared the
      translation of 5'-capped RNA to noncapped RNA. The translation of 5'-capped RNA
      was higher, as expected. Consequently, ribosomal frameshifting producing the Gag
      Pro polypeptide was enhanced when compared to the translation of noncapped RNA.
      Taken together these results indicate that efficiencies of translation, in
      conjunction with the cis regulatory genetic elements at the frameshift sites,
      determine the ratio of the polypeptides Gag, Gag-Pro, and Gag-Pro-Pol produced in
      the HTLV-infected cell. Thus, physiological changes which affect the cellular
      translation machinery may alter the optimal ratio of these three polyprotein
      products needed for virus maturation.

PMID- 11831714
TI  - Coronavirus defective-interfering RNA as an expression vector: the generation of
      a pseudorecombinant mouse hepatitis virus expressing hemagglutinin-esterase.
AB  - We have developed an expression vector system using a defective-interfering (DI)
      RNA of mouse hepatitis virus (MHV), a prototype coronavirus, to deliver and
      express a foreign gene in MHV-infected cells. This vector contains an MHV
      intergenic sequence to promote the expression of foreign genes. In this study, we
      used this vector to introduce a hemagglutinin-esterase (HE) protein, an optional
      MHV structural protein, into the MHV-infected cells. The engineered HE protein
      could be efficiently incorporated into the virion which did not synthesize its
      own HE protein, thus generating a pseudorecombinant virus that expresses an
      exogenous HE protein. The engineered HE protein could be made distinguishable
      from the native protein by attaching an 8-amino-acid peptide tag at the carboxyl
      terminus. Both the engineered and native HE proteins from the HE-producing virus
      train could be incorporated into the virion, thus generating phenotypically mixed
      virus particles. We also showed that the HE-expressing DI RNA could be
      incorporated into viruses, and the engineered HE protein expressed in the
      infected cells for at least three serial virus passages. Furthermore, we have
      made two mutants, in which parts of the external domain of the HE protein have
      been deleted, to study the sequence requirements for the stable expression of HE
      and its incorporation into MHV virions. Although both of the mutant HE proteins
      could be expressed in the MHV-infected cells, they failed to be incorporated into
      virions, suggesting the importance of the extracellular domain of HE protein for
      its incorporation into virus particles. This vector system enabled the first
      successful incorporation of a selected coronaviral protein into virions and
      demonstrates its utility as an expression vector for studying the molecular
      biology of coronaviruses.

PMID- 11831715
TI  - Passage of Autographa californica nuclear polyhedrosis virus through the midgut
      epithelium of Spodoptera exigua larvae.
AB  - A special recombinant of Autographa californica multicapsid nuclear polyhedrosis
      virus (AcNPV) was designed to study the early histopathological events of
      baculovirus infection in Spodoptera exigua larvae. This recombinant contained a
      Drosophila melanogaster heat shock 70 promoter driving an Escherichia coli beta
      galactosidase (Lac-Z) reporter gene to monitor the presence of early viral gene
      expression and a second reporter gene, the E. coli beta-glucuronidase (GUS) gene,
      under control of the very late AcNPV p10 promoter to monitor viral replication.
      In S. exigua larvae, permissive Spodoptera spp. cultured cells, and nonpermissive
      D. melanogaster cultured cells early viral gene expression was indicated by the
      appearance of Lac-Z as early as 3 hr p.i. Late viral gene expression was
      indicated by the appearance of GUS and occurred only in the permissive cultured
      cells and larvae. Early and late viral gene expression could be detected
      simultaneously using differential enzyme histochemistry. Analysis of infected S.
      exigua larvae revealed that midgut columnar cells and, at a low frequency, midgut
      regenerative cells were the primary sites of infection. Parental nucleocapsids
      were apparently transported through columnar cells to underlaying regenerative
      cells before virus replication and progeny production. Infection of tissues
      beside the midgut epithelium was not detected prior to viral replication within
      the midgut, suggesting that infection of the midgut is an important prelude to
      systemic infection.

PMID- 11831716
TI  - Rat monoclonal antibodies differentiating between the Epstein-Barr virus nuclear
      antigens 2A (EBNA2A) and 2B (EBNA2B).
AB  - Rat monoclonal antibodies were produced against the C-terminus of Epstein-Barr
      virus nuclear antigens 2A (EBNA2A) and 2B (EBNA2B) expressed as bacterial trpE
      fusion proteins. The initial screening was performed using a soluble bacterial
      extract containing the fusion proteins. Positive hybridomas were confirmed by
      immunofluorescence on SF158 (Spodoptera frugiperda) insect cells infected with
      recombinant baculovirus (Autographa californica nuclear polyhedrosis virus) and
      expressing the complete EBNA2A or EBNA2B genes. We selected a panel of antibodies
      which reacted either with both antigens or specifically with EBNA2A or with
      EBNA2B. The antibodies were extensively characterized using immunoprecipitation,
      Western blotting, epitope mapping on synthesized peptide segments of EBNA2A,
      immunocytology, and immunohistology on both cryostat sections and paraffin
      sections of AIDS-associated primary central nervous system lymphomas.

PMID- 11831717
TI  - Sequence and repeat structure variants in the long terminal repeat of maedi-visna
      virus EV1.
AB  - Diversity in the LTR of maedi-visna virus strain EV1 has been examined by PCR
      based gene amplification using DNA from infected cells both in vitro and in
      experimentally infected animals. In vitro, several variant structures were found
      in the U3 regions of the LTR which contained repeats of sequences including
      presumed AP-1 and AP-4 binding sites. Although these repeat variants formed a
      minor fraction of the LTRs present in the proviral population, they were neither
      produced nor lost at a significant rate when PCR was performed on cloned viral
      DNA and so were unlikely to be artefacts of the isolation procedure. When LTRs
      were isolated from two experimentally EV1 infected sheep, repeat variant
      structures were found to be present in efferent lymph by 14 days postinfection
      (p.i.) (although not seen at 9 days p.i.). They were also present at later times
      and in blood. Overall sequence diversity at 9 days p.i. was reduced compared both
      with the infecting virus and with later times of infection. When a number of the
      variant LTR structures were used to drive CAT reporter gene constructs in
      chondrocytes, all were found to be active, although consistent differences of up
      to fourfold in activity were seen. However, there is no evidence from these data
      for strong selective pressure operating on the LTR in vivo.

PMID- 11831718
TI  - The complete nucleotide sequence of RNA 3 of a peach isolate of Prunus necrotic
      ringspot virus.
AB  - The complete nucleotide sequence of RNA 3 of the PE-5 peach isolate of Prunus
      necrotic ringspot ilarvirus (PNRSV) was obtained from cloned cDNA. The RNA
      sequence is 1941 nucleotides and contains two open reading frames (ORFs). ORF 1
      consisted of 284 amino acids with a calculated molecular weight of 31,729 Da and
      ORF 2 contained 224 amino acids with a calculated molecular weight of 25,018 Da.
      ORF 2 corresponds to the coat protein gene. Expression of ORF 2 engineered into a
      pTrcHis vector in Escherichia coli results in a fusion polypeptide of
      approximately 28 kDa which cross-reacts with PNRSV polyclonal antiserum. Analysis
      of the coat protein amino acid sequence reveals a putative "zinc-finger" domain
      at the amino-terminal portion of the protein. Two tetranucleotide AUGC motifs
      occur in the 3'-UTR of the RNA and may function in coat protein binding and
      genome activation. ORF 1 homologies to other ilarviruses and alfalfa mosaic virus
      are confined to limited regions of conserved amino acids. The translated amino
      acid sequence of the coat protein gene shows 92% similarity to one isolate of
      apple mosaic virus, a closely related member of the ilarvirus group of plant
      viruses, but only 66% similarity to the amino acid sequence of the coat protein
      gene of a second isolate. These relationships are also reflected at the
      nucleotide sequence level. These results in one instance confirm the close
      similarities observed at the biophysical and serological levels between these two
      viruses, but on the other hand call into question the nomenclature used to
      describe these viruses.

PMID- 11831719
TI  - Identification of a neutralizing epitope on an 82-kDa protein encoded by gene 3
      of group C rotavirus.
AB  - A neutralizing monoclonal antibody (1A5) with hemagglutination inhibition
      activity was produced against a cultivable porcine group C rotavirus strain
      (strain AmC-1) and used to identify and map the functional topography of the
      protein involved in viral neutralization. The 1A5 mAb recognized an 82-kDa
      protein from infected cells as well as an equivalent in vitro-translated protein
      programmed with gene 3 of the AmC-1 strain. By employing a method called DNA
      amplification-restricted transcription-translation a series of C-terminal
      truncated fragments of the 82-kDa protein was produced. Immunoprecipitation
      experiments show that 1A5 recognizes an epitope located on vp5, a tentative
      trypsin cleavage fragment of the 82-kDa protein. The functional and antigenic
      topography on the 82-kDa protein is discussed in relation to vp4 of group A
      rotavirus.

PMID- 11831720
TI  - Analysis of human immunodeficiency virus type 1 promoter insertion in vivo.
AB  - Our study reports the occurrence of HIV-1 insertional activation events in vivo.
      Using a previously described PCR assay, small aliquots of broncho-alveolar lavage
      (BAL) cells obtained from AIDS patients were analyzed. Nine percent (5/54) of the
      aliquots contained proviral-host sequence transcripts indicating HIV-1 promoter
      insertion, whereas multiply spliced HIV-1 mRNAs were found in 28% (15/54) of the
      aliquots. In four of five events, insertions affect distinct cellular
      transcription units expressed in a T-cell line. To establish a ratio between
      provirus integration and promoter insertion events, an in vitro infection study
      was performed and transcripts containing HIV-1 and K-ras or CD4 gene sequences,
      respectively, were monitored. Given the randomness of retrovirus integration, 170
      sense-oriented HIV integrations into these gene loci were predicted to occur.
      Three distinct promoter insertion events were observed, indicating that 1.8% of
      integrated proviruses transcribed adjacent genes. Based on this result and a mean
      of 257 proviral copies per 10(6) BAL cells, we would expect to observe 25
      promoter insertion events in our in vivo study. That only five events were found
      may be due to the lower transcriptional activity of HIV-1 in vivo than that in
      cell cultures.

PMID- 11831721
TI  - The tomato bushy stunt virus replicase proteins are coordinately expressed and
      membrane associated.
AB  - Two open reading frames at the 5'-end of the tomato bushy stunt virus genomic RNA
      are predicted to encode a 33-kDa (p33) protein and its 92-kDa (p92) readthrough
      product. From amino acid sequence comparisons with other small single-stranded
      RNA viruses, these proteins resemble viral components of the replicase
      transcriptase complex. To investigate the accumulation of these proteins in the
      infected cell, two chimeric proteins were produced that expressed either a
      portion of p33 or the carboxy-terminal "half" of p92 fused with glutathione S
      transferase, and polyclonal ascites fluids specific to p33 or p92 were elicited
      in mice. As expected, the anti-p33 antibody recognized p33 and the p92
      readthrough protein, but the anti-p92 antibody was specific for p92. Immunoblot
      analyses revealed that at an early stage of infection both proteins were
      associated with the membrane fractions isolated from virus-infected plants, but
      later in the infection, prior to collapse of the tissues, these proteins were
      also associated with the cytoplasmic fraction. At all time points in plants and
      protoplasts p33 was about 20-fold more abundant than p92. A series of mutations
      derived from an infectious cDNA clone demonstrated that both the p33 and the p92
      proteins were required for replication in protoplasts and the ratio of the two
      proteins was maintained in the replication-competent mutants. The wild-type amber
      (UAG) and in vitro-generated ochre (UAA) readthrough codon derivatives replicated
      in protoplasts. However, the tyrosine mutants (UAC or UAU) that were predicted to
      express only p92 were not viable in protoplasts.

PMID- 11831722
TI  - Foreign complementary sequences facilitate genetic RNA recombination in brome
      mosaic virus.
AB  - We have demonstrated that local antisense sequences can mediate genetic
      recombination within the 3' noncoding region among brome mosaic virus (BMV) RNAs
      (P. Nagy and J. J. Bujarski, 1993, Proc. Natl. Acad. Sci. USA 90, 6390-6394).
      Here we show that foreign complementary inserts can direct crossovers between BMV
      RNA3 components within an internal region. A 170-nt polynucleotide derived from
      the cowpea chlorotic mottle virus (CCMV) RNA3 was inserted just upstream of the
      initiation codon of the BMV coat protein open reading frame in either sense or
      antisense orientations. The resulting respective mutants, BCC+ and BCC-,
      maintained unchanged CCMV inserts when inoculated separately on leaves of a local
      lesion host for BMV. In contrast, when a mixture containing both mutated RNAs3
      was inoculated, a significant fraction of lesions accumulated the BMV RNA3
      lacking the CCMV insert. The presence of a 3' marker mutation confirmed that the
      BMV RNA3 progeny arose due to crossovers between BCC+ and BCC- within the
      complementary sequences. The highest frequency of recombinant appearance was
      observed when the RNA mixtures were annealed prior to inoculation on the host
      plants. Our results confirm a concept predicting the general nature of the
      heteroduplex-mediated recombination functioning in RNA viruses. Examples of
      possible applications of this approach in recombinant RNA technology are
      discussed.

PMID- 11831723
TI  - The acidic amino-terminal region of varicella-zoster virus open reading frame 4
      protein is required for transactivation and can functionally replace the
      corresponding region of herpes simplex virus ICP27.
AB  - Both varicella-zoster virus open reading frame 4 (ORF4) protein and its herpes
      simplex virus type 1 homolog ICP27 have highly acidic amino-terminal regions and
      cysteine-rich carboxy-terminal regions. To investigate the functional domains of
      these proteins, mutants were constructed and their transregulatory functions were
      tested in transient expression assays using two reporter plasmids, pTK-CAT-SV40A
      and pTK-CAT-synA, containing the same promoter sequences but different mRNA
      processing signals. ORF4 transactivates both pTK-CAT-SV40A and pTK-CAT-synA,
      while ICP27 transrepresses pTK-CAT-SV40A and transactivates pTK-CAT-synA.
      Deletion of the ORF4 amino-terminal region abolished most of the transactivating
      activity for pTK-CAT-synA but retained most of the transactivating activity for
      pTK-CAT-SV40A. Construction of chimeric ORF4-ICP27 molecules indicated that the
      ORF4 amino-terminal region was able to replace the corresponding region of ICP27
      which is required for both transrepression of pTK-CAT-SV40A and transactivation
      of pTK-CAT-synA. Similarly, the ICP27 amino-terminal region was able to partially
      replace the corresponding region of ORF4 which is required for transactivation of
      pTK-CAT-synA Thus, while ORF4 and ICP27 have different properties in transient
      expression assays, the amino-terminal regions of ORF4 and ICP27 are functionally
      homologous to each other and are important in regulating gene expression.

PMID- 11831724
TI  - Influenza A virus RNA polymerase subunit PB2 is the endonuclease which cleaves
      host cell mRNA and functions only as the trimeric enzyme.
AB  - The influenza A virus RNA-dependent RNA polymerase catalyzes several reactions in
      transcription and replication of the genome RNA. The first step in viral mRNA
      synthesis is the endonucleolytic cleavage of host cell mRNAs containing a cap
      structure to generate capped primers that are 10-14 nucleotides long which are
      then used to prime transcription of virus-specific mRNAs. To analyze the
      properties of the capped RNA-specific endonuclease associated with the influenza
      virus polymerase and the roles of each of the three subunits in transcription
      initiation, we established an in vitro assay to investigate this endonucleolytic
      cleavage reaction. This assay consists of an artificial RNA substrate containing
      a cap-0 structure at its 5' end and a partial alfalfa mosaic virus RNA 4 (AIMV
      RNA 4) sequence which had been shown to be cleaved by the influenza polymerase.
      Results showed that purified virion ribonucleoprotein complexes cleaved the RNA
      substrate specifically to generate a capped 14-nt RNA fragment for use as primer
      to initiate viral mRNA synthesis. Purified polyclonal anti-PB2 IgG inhibited the
      endonuclease activity, but anti-PB1 and anti-PA antibodies did not inhibit the
      cleavage. Partially purified trimeric polymerase expressed by recombinant
      baculovirus in insect cells cleaved the artificial substrate, but if one or two
      subunits were removed from the polymerase complex, the cleavage activity was
      totally lost. Our results suggest that viral PB2 protein is the endonuclease that
      cleaves host cell mRNA to produce the primer used to initiate transcription;
      however, association with the other two enzyme subunits seems to be required for
      this PB2 function.

PMID- 11831725
TI  - Defective RNA molecules associated with citrus tristeza virus.
AB  - Preparations of single-stranded (ss) RNA extracted from particles of the Israeli
      VT strain of citrus tristeza virus (CTV-VT), and ss- and double-stranded (ds) RNA
      preparations extracted from infected Alemow (Citrus macrophylla) plants,
      contained a population of molecules with features that suggest that they are
      defective RNAs. The prototype of 2424 nt was cloned and sequenced and was found
      to be composed of two genomic regions corresponding to the 5' (1151 nt) and the
      3' (1259 nt) termini of the genomic CTV-RNA, with two perfect direct repeats of
      eight nucleotides of unknown origin at the junction site. Northern hybridization
      analysis demonstrated that this 2.4-kb defective RNA is an abundant species among
      the other CTV-specific ss- and ds-RNAs in infected plants. The 2.4-kb RNA was
      found encapsidated by the CTV coat protein indicating that the CTV origin of
      assembly is located close to the 5' or 3' terminus. This is the first defective
      RNA to be reported for a member of the closterovirus group.

PMID- 11831726
TI  - Nef and LTR sequence variation from sequentially derived human immunodeficiency
      virus type 1 isolates.
AB  - Variation in HIV-1 nef and LTR DNA sequences was assessed longitudinally during
      disease progression in four HIV-1-infected subjects. Point mutations were found
      among quasispecies obtained at a single time point in each individual, with
      increasing diversity with disease progression in two of three patients for whom
      sufficient data were available for analysis. Deletions and rearrangements were
      more common in late than early stages of disease. Continued sequence evolution in
      HIV-1 quasispecies with nef deletions along with coexistence of nef-bearing
      quasispecies suggest that nef-deleted quasispecies are capable of replication in
      vivo, possibly complemented by quasispecies lacking such deletions and/or by
      adaptation to a specialized niche within the patients.

PMID- 11831727
TI  - Characterization of the hepatitis B virus large surface antigen promoter Sp1
      binding site.
AB  - A binding site for the transcription factor Sp1 was identified in the hepatitis B
      virus (HBV) large surface antigen promoter between nucleotides -49 and -29 by
      DNase I footprinting analysis with purified recombinant Sp1 protein. Gel
      retardation analysis using Huh7 nuclear extracts demonstrated that formation of
      complexes between this sequence element and DNA-binding proteins was specifically
      inhibited by the HBV major surface antigen and nucleocapsid promoter Sp1 binding
      sites, as well as by the Sp1 consensus recognition sequence. In addition, gel
      supershift analysis showed that this sequence element bound factor(s) present in
      Huh7, HeLa S3, and HepG2.1 cell nuclear extracts which were completely
      supershifted by the Sp1 antibody and appeared to be the same or similar to the
      factor(s) which bound the consensus Sp1 recognition sequence. The function of the
      large surface antigen promoter Sp1 recognition sequence was examined by transient
      transfection analysis in Drosophila melanogaster Schneider line-2 (SL2) cells. In
      the context of a minimal promoter element, this Sp1 site was able to mediate
      transcriptional transactivation by exogenously expressed Sp1. These results
      suggest that the HBV large surface antigen promoter contains a functional Sp1
      binding site which may be involved in the coordinate regulation of HBV
      transcription by the ubiquitous transcription factor Sp1.

PMID- 11831728
TI  - N-terminal basic amino acids of alfalfa mosaic virus coat protein involved in the
      initiation of infection.
AB  - Alfalfa mosaic virus coat protein or its messenger RNA is required in the
      inoculum for virus infection. The N-terminus of the coat protein is required for
      activity; thus, changes were made in the amino acid sequence of this region. Six
      coat protein mutants were tested for activity in virus infection assays in
      protoplasts. A coat protein mutant in which N-terminal residues 3-19 were absent
      was inactive; whereas, a mutant in which residues 3-11 were absent (CP deltaN9)
      still had 73% of wild-type activity. Substitution of alanine for the basic
      residues at positions 14, 17, and 18 in full-length coat protein and in CP
      deltaN9 resulted in mutant proteins that were inactive in infection. Thus, one,
      two, or three of these basic residues in CP are required for activity.

PMID- 11831729
TI  - Intracellular phosphorylation of the Sendai virus P protein.
AB  - Phosphorylation status of the Sendai virus P protein was examined during virus
      infection and compared with cell-free phosphorylation. P protein from Sendai
      virus-infected (VI) and P/C gene-transfected (PT) mammalian cells and from
      purified virions (PV) was phosphorylated at only serine residues. In contrast,
      cell-free phosphorylation of the P protein with virion-associated protein kinase
      (VAPK) occurred at both threonine and serine. Tryptic phosphopeptide maps of the
      P protein from VI, PT, and PV showed that the phosphorylation was primarily
      localized on one peptide (TP1), while VAPK phosphorylated the P protein on
      several peptides. There was no change in the steady-state phosphopeptide map of
      the P protein during virus replication, indicating that the TP1 is constitutively
      phosphorylated. Inhibition of cellular phosphatases (PP1 and PP2A) by okadaic
      acid (OA) in virus-infected cells caused a sixfold increase in the P protein
      phosphorylation, solely at serine residues. The phosphopeptide map of the OA-P
      protein revealed that phosphorylation occurred on several peptides, but the OA-P
      map was significantly different from the VAPK-P map. However, additional
      phosphorylation of the P protein did not block its association with
      nucleocapsids. These results suggest that the Sendai virus P protein is
      constitutively phosphorylated primarily at one locus but has the potential for
      phosphorylation at additional sites. Further, our results do not show any
      correlations between the intracellular and cell-free phosphorylation of the P
      protein and, therefore, question the validity of cell-free phosphorylations.

PMID- 11831730
TI  - Identification, expression, and processing of an 87-kDa polypeptide encoded by
      ORF 1a of the coronavirus infectious bronchitis virus.
AB  - Nucleotide sequence analysis has shown previously that the genomic-length mRNA
      (mRNA1) of the coronavirus infectious bronchitis virus (IBV) contains two large
      open reading frames (ORFs), 1a and 1b, with the potential to encode polyproteins
      of approximately 441 and 300 kDa, respectively. We have characterized the
      specificity of a set of region-specific antisera raised against the 5'-portion of
      ORF 1a by immunoprecipitation of in vitro-synthesized, C-terminally truncated 1a
      polypeptides and used these antisera to detect virus-specific proteins in IBV
      infected Vero cells. Two antisera, which had specificity for IBV sequences from
      nucleotides 710 to 2079 and 1355 to 2433, respectively, immunoprecipitated a
      polypeptide of approximately 87 kDa from IBV-infected Vero cells. In vitro
      translation of ORF 1a sequence terminating at nucleotide 5763 did not produce
      this protein unless the in vitro translation products were incubated with Vero
      cell S10 extracts prepared from either IBV-infected or mock-infected Vero cells.
      However, processing of the 87-kDa protein was also observed when the same region
      was expressed in Vero cells using the vaccinia virus/T7 expression system. This
      observation indicates that the 87-kDa polypeptide is encoded within the 5'-most
      3000 nucleotides of mRNA 1 and that it might be cleaved from the 1a polyprotein
      by viral and cellular proteinases.

PMID- 11831731
TI  - Differential effects of satellite RNA on the accumulation of cucumber mosaic
      virus RNAs and their encoded proteins in tobacco vs zucchini squash with two
      strains of CMV helper virus.
AB  - The presence of cucumber mosaic virus (CMV) satellite RNA usually reduces the
      yield of accumulated helper virus, although more so in solanaceous than in
      cucurbit hosts. The accumulation of viral RNA and viral-encoded proteins of two
      strains of CMV (Fny- and Sny-) known to differ in their ability to support
      satellite RNA in zucchini squash was examined in squash and tobacco to determine
      the effect of satellite RNA on the accumulation of viral-associated components.
      In the absence of satellite RNA, Fny- and Sny-CMV showed similar levels of
      accumulation of RNA at 7 days postinoculation (p.i.), but by 14 days p.i. the Fny
      CMV RNAs accumulated to lower levels than did both strains at 7 days p.i., in
      either host. The levels of accumulated Sny-CMV-encoded proteins were higher than
      those encoded by Fny-CMV in tobacco, but not squash plants, at 7 days p.i. At 14
      days p.i., for Fny-CMV vs Sny-CMV, there were differences in the levels of
      accumulation of most CMV-encoded proteins in both hosts, more exacerbated in
      tobacco vs squash. The effect of satellite RNA was to intensify these
      differences; that is, by 7 days p.i., satellite RNA reduced the accumulation of
      Fny-CMV RNAs 1 and 2 and their encoded proteins in both tobacco and squash but
      had little or no effect on the accumulation of Sny-CMV RNAs or encoded proteins.
      By 14 days p.i., the levels of accumulation of all Fny-CMV RNAs and encoded
      proteins were severely reduced in both hosts, and the levels of accumulation of
      Sny-CMV RNAs 1 and 2 and their encoded proteins were also reduced in tobacco, but
      not squash. Sny-CMV did not support satellite RNA accumulation in squash plants
      or protoplasts. Satellite RNA did not appear to have a direct effect on the
      movement of either CMV strain. Rather, accumulation studies in tobacco
      protoplasts indicated that the difference in response of Fny-CMV vs Sny-CMV to
      satellite RNA in tobacco was due to the extent to which satellite RNA affected
      the levels of RNA 1, and to a lesser extent RNA 2, and their encoded proteins, 1a
      and 2a, both components of the CMV replicase.

PMID- 11831732
TI  - Localization of neurovirulence determinant for rats on the S1 subunit of murine
      coronavirus JHMV.
AB  - A cloned virus of murine coronavirus JHMV, cl-2, was shown to be highly
      neurovirulent for rats in comparison with other JHMV variants. We have isolated
      cl-2-derived variant viruses resistant to neutralization by monoclonal antibodies
      (MAbs) specific for the spike (S) protein of cl-2. The variants MM6 and MM13,
      selected by the MAbs specific for the JHMV S protein, were revealed to have a
      point mutation located within the N-terminal 100 amino acids (aa) of the S1
      protein. The variants MM56, MM85, and MM78, selected by MAbs specific for the
      larger S protein of JHMV, were shown to have a deletion composed of about 150 aa
      located in the middle of the S1 subunit (MM56 and MM85) or one amino acid
      deletion, aspartic acid at number 543 from the N-terminus of the S1 (MM78). These
      five MAb-resistant variants were not different from cl-2 in growth pattern on
      cultured DBT cells. MM6 and MM13 were shown to be highly neurovirulent for 4-week
      old Lewis rats, growing to high titers in the brain and causing as high an
      incidence of neurological disease and death as the parental cl-2. In contrast,
      MM56 and MM85 were nonneurovirulent for rats. They did not cause any central
      nervous system disorders nor did they multiply in the rat brains. MM78 showed
      intermediate neurovirulence as well as intermediate growth potential in the rat
      brain. However, there was no apparent difference in neurovirulence between the
      parental and the MAb-resistant variants for mice; all of these viruses showed
      high neurovirulence for mice. These results suggest that the domain composed of
      about 150 aa in the middle of the S1 is critical for high neurovirulence of JHMV
      for rats. Furthermore, it is suggested that the neurovirulence of cl-2 for mice
      is controlled by a different viral factor.

PMID- 11831733
TI  - Resistance to retroviral infection in transgenic and bone marrow chimeric mice
      containing Fv4-env-expressing hematopoietic cells.
AB  - Mice and chickens that inherit certain retroviral envelope genes are resistant to
      infection with related retroviruses. Previously, we described two transgenic
      mouse strains bearing a retroviral envelope gene, Fv4, that confers resistance to
      infection with ecotropic retroviruses (T. I. Limjoco et al., 1993, J. Virol. 67,
      4163-4168). Here, we present results with these and an additional transgenic
      strain that show that (1) the level of resistance is correlated with level of
      expression of the transgene, (2) low-level expression of the transgene is
      associated with an unexpected and possibly immune-mediated phenotype of recovery
      from viremia, (3) resistance can be transferred by bone marrow transplantation
      and is "dominant" in chimeras containing mixtures of transgenic resistant plus
      control bone marrow, and (4) transplantation after infection with Friend Virus is
      much less effective than transplantation before infection. We discuss the
      implications of these results for gene therapy of retroviral infection.

PMID- 11831734
TI  - The larger genomic RNA of Helicoverpa armigera stunt tetravirus encodes the viral
      RNA polymerase and has a novel 3'-terminal tRNA-like structure.
AB  - In this paper we report the complete nucleotide sequence of the larger segment
      (5312 nucleotides) of the bipartite RNA genome of Helicoverpa armigera stunt
      tetravirus (HaSV). HaSV therefore becomes the first member of the Tetraviridae, a
      virus family with a host range restricted to lepidopteran insects, whose genome
      has been completely sequenced. HaSV RNA 1 encodes a 187K protein which includes
      three domains conserved in RNA-dependent RNA polymerases of RNA viruses in the
      alpha-like superfamily. Analysis of the replicase sequence confirms the status of
      the Tetraviridae as a distinct family within this superfamily, which includes
      animal, plant, and insect viruses, and shows the least-distantly related
      replicase for all three domains to be that of the hepatitis E virus. Another
      feature of the nonpolyadenylated HaSV genomic RNAs is a well-conserved 3'
      terminal tRNA-like structure, the first such structure discerned in an animal
      virus. However, in contrast to the tRNA-like structures on some plant virus RNAs,
      the HaSV structure, which has a valine anticodon (CAU), appears to form without a
      pseudoknot and therefore resembles authentic tRNA(Val) more closely than do the
      plant viral structures. The implications of these observations for our
      understanding of RNA virus evolution are discussed.

PMID- 11831735
TI  - Synthesis and processing of equine herpesvirus 1 glycoprotein D.
AB  - Previous studies (C. C. Flowers and D. J. O'Callaghan, 1992, Virology 190, 307
      315) employed peptide-specific antibodies to identify the product of the
      glycoprotein D (gD) gene of equine herpesvirus 1 strain Kentucky A (KyA). gD
      polypeptides of 55 and 58 kDa were detected in EHV-1-infected L-M cells, and the
      58-kDa protein was observed in the membrane fraction of EHV-1 virions. In this
      report, the kinetics of synthesis and processing of gD polypeptides are
      described. One-hour pulse-labeling of EHV-1-infected L-M cells revealed that gD
      proteins are first detected at 6 hr after infection and that maximal synthesis of
      gD occurs between 5 and 8 hr postinfection. gD polypeptides accumulate
      progressively with time of infection as shown by immunoprecipitation analysis of
      gD proteins. Pulse-chase analysis of gD revealed that the 55-kDa protein is a
      precursor to the 58-kDa species and that processing of all pulse-labeled
      precursor protein requires approximately 2.5 hr. Analysis of the carbohydrate
      content of gD proteins, as judged by their sensitivity to digestion with
      endoglycosidases, revealed that the 55-kDa gD precursor contains high-mannose N
      linked oligosaccharides, while the 58-kDa gD mature polypeptide possesses complex
      type oligosaccharides. Expression of the mature form of gD on the cell surface,
      as determined by fluorescent flow cytometric analysis, is delayed compared to the
      accumulation of the mature form of gD within the cell. The gD ORF encodes a
      potential protein of 442 amino acids but analysis of the translated sequence of
      gD indicated that the gD polypeptide is 392 amino acids, a size predicted by
      previous mapping of the transcription start site of the gD mRNA. Coupled in vitro
      transcription/translation of a pGEM-3Z construct containing the 392-amino-acid gD
      ORF, in the absence or presence of canine pancreatic microsomes, demonstrated
      that the 43-kDa gD polypeptide undergoes processing in vitro. These studies
      demonstrate that the EHV-1 strain KyA gD is processed in a fashion similar to
      that of the gD proteins of other alphaherpesviruses.

PMID- 11831736
TI  - Genome structure and phylogenetic analysis of lettuce infectious yellows virus, a
      whitefly-transmitted, bipartite closterovirus.
AB  - We report the complete nucleotide sequences of lettuce infectious yellows virus
      (LIYV) RNAs 1 and 2. LIYV RNA 1 is 8118 nucleotides and includes three open
      reading frames (ORFs). Computer-assisted analysis of LIYV RNA 1 ORFs identified
      domains for a papain-like protease, methyltransferase (MTR), RNA helicase (HEL),
      and RNA-dependent RNA polymerase (RdRp). We suggest that the RdRp domain is
      expressed independently of the other replication-associated domains via a + 1
      ribosomal frameshift. Amino acid sequences of the MTR, HEL, and RdRp show highly
      significant similarity to the homologous sequences from other closteroviruses and
      lower similarity to the respective proteins of tobamoviruses, tobraviruses,
      hordeiviruses, bromoviruses, and furoviruses. LIYV RNA 2 is 7193 nucleotides and
      includes six ORFs. These ORFs include a gene array that is characteristic of the
      closteroviruses: ORFs encoding a small membrane protein, a homologue of the HSP70
      family of chaperone proteins, a protein whose function is unknown, the coat
      protein, and a diverged duplicate of the coat protein. LIYV is distinguished from
      the monopartite closteroviruses in the following ways: its genome consists of two
      RNAs, the positions of the coat protein gene and its diverged duplicate are
      reversed, and LIYV includes ORFs that are unrelated to ORFs found in other
      closteroviruses.

PMID- 11831737
TI  - Recommendations for the health monitoring of rodent and rabbit colonies in
      breeding and experimental units.

PMID- 11831738
TI  - Airborne contaminants in conventional laboratory rabbit rooms.
AB  - Besides the well known allergens, several other risk factors may exist for health
      in a laboratory animal unit. The exposure to these factors may be significant in
      animal units with poor general or local ventilation systems. Moreover, means to
      prevent the distribution of airborne contaminants may be limited in animal units
      housing rabbits or other bigger laboratory animals. Airborne contaminants in
      conventional laboratory rabbit rooms were sought to evaluate the occupational
      exposure of animal care personnel. Concentrations of airborne dust, bacteria,
      fungi, ammonia and endotoxins were measured during 2 days in three phases: before
      working activities began, during them and afterwards. Both stationary and some
      personal samples were taken. All of the contaminants sought were found in the
      rabbit room air. When compared to reported levels in farm animal production
      areas, the concentrations measured were generally low. However, moderate or high
      levels of airborne bacteria and fungi were found occasionally during work
      routines. Airborne contaminants should be considered as a potential occupational
      health risk for persons working with laboratory animals.

PMID- 11831739
TI  - Diagnosis of sexual cycle by means of vaginal smear method in the chinchilla
      (Chinchilla lanigera).
AB  - An investigation was made as to whether the sexual cycle and pregnancy can be
      determined by means of vaginal smear in chinchillas. This study represents the
      first attempt to record changes which occur in the pattern of exfoliated cells in
      chinchilla's vaginal smear during anoestrus, proestrus, oestrus, metoestrus and
      pregnancy. Fifteen female chinchillas aged from 8 months to 3 years and bred
      through harem breeding method were used. The major change during proestrus was an
      increase in the proportion of superficial cells, with a corresponding decrease in
      other cells. Goblet cells were observed in the smears prepared by strong
      aspiration during this cycle. Neutrophils, small and large intermediates and
      parabasal cells were not found in the smear during oestrus and the smear
      consisted of superficial cells only. In the proportion of neutrophils, small and
      large intermediates and parabasal cells increased during metoestrus. In addition,
      metoestrum and foam cells were found in this cycle. In anoestrus; superficial and
      parabasal cells were present in small numbers. Also small and large intermediate
      cells as well as neutrophils were present. Traces of foam and metoestrum cells
      were found. During pregnancy, neutrophils generally of medium density were
      present, parabasal; small and large intermediate cells were present at low or
      medium density, and superficial cells were only present in trace amounts.

PMID- 11831740
TI  - Atrichia with papular lesions resulting from mutations in the rhesus macaque
      (Macaca mulatta) hairless gene.
AB  - Atrichia with papular lesions (APL) is a rare form of hair loss with an autosomal
      recessive mode of inheritance that is characterized by the absence of normal hair
      follicles, and formation of intradermal cystic structures. Mutations in the
      hairless (hr) gene in mice and humans have been implicated in the development of
      this phenotype. Hairless is a putative transcription factor containing a single
      zinc-finger DNA binding domain, with restricted expression in brain and skin.
      Here, we describe the complete hr cDNA sequence from the rhesus macaque (Macaca
      mulatta) and report the identification of a compound heterozygous mutation in a
      hairless rhesus macaque born from unrelated parents. Cutaneous biopsy samples
      from the affected macaque revealed abnormalities, including the replacement of
      normal hair follicles with dermal cysts and comedones, reminiscent of the skin
      phenotype observed in hairless mice and humans with APL.

PMID- 11831741
TI  - Macroscopic and roentgenographic anatomy of the skull of the ferret (Mustela
      putorius furo).
AB  - Normal macroscopic and roentgenographic features of the skull of the ferret
      (Mustela putorius furo) were examined and described. Data were based on a sample
      of 100 (50 male and 50 female) adult ferrets of known body weight and age. The
      skull was described macroscopically according to six standard views, i.e. dorsal,
      lateral, ventral, caudal, cranial and midsagittal. The mandible was described
      separately. The roentgenographic characteristics of the ferret skull were
      demonstrated only in lateral and dorsoventral projections. Furthermore, the skull
      length and width as well as the minimum frontal width were measured, and skull
      indices were derived from relevant measurements. Sexual dimorphism was examined
      both morphologically and craniometrically. Besides the common features of a
      carnivore skull, the ferret skull is relatively elongated and flat with a short
      facial region. The skulls of adult male ferrets are about 17% longer and 22%
      wider than those of the females. Significant sexual dimorphism also exists
      regarding certain skull indices. The general features and some dimensional
      parameters of the adult ferret skull support the contention that the ferret would
      be an interesting and workable alternative animal model in craniofacial research.

PMID- 11831742
TI  - Effect of vitamin E supplementation on lipid peroxidation in blood and lung of
      influenza virus infected mice.
AB  - The influenza virus infection (A/Aichi/2/68) was associated with development of
      oxidative stress in lung and blood of mice, accompanied by an increase in levels
      of lipid peroxidation products (conjugated dienes and total malondialdehyde) and
      a decrease in endogenous amounts of natural antioxidant vitamin E. These effects
      were most pronounced on the 5th day after virus inoculation, in comparison with
      those on the 7th. Supplementation of mice with exogenous vitamin E before virus
      inoculation lead to lung and blood protection against lipid peroxidation. A
      marked decrease in lipid peroxidation products and an increase in vitamin E
      content was established in blood and lung on the 5th and 7th day after virus
      inoculation. The stabilizing effect of vitamin E is dose-dependent in blood and
      dose-independent in lung, and was most pronounced on the 5th day after virus
      inoculation in comparison with the 7th day.

PMID- 11831743
TI  - Histamine production by Haemophilus somnus.
AB  - Ten Haemophilus somnus isolates were grown on blood agar plates under a 5% CO2
      atmosphere for 48 h. Harvested whole cells were washed and evaluated for the
      presence of histamine by ELISA. All H. somnus isolates had cell-associated
      histamine concentrations of between 18.5 and 200 ng/ml. In a separate study, the
      ability of H. somnus to secrete histamine into BHI growth medium was evaluated
      using H. somnus strains 8025 and 156A as well as a recent 156A respiratory
      isolate. Each strain or isolate was grown under various concentrations of CO2 to
      approximate the CO2 concentration in the bronchi. The histamine content of washed
      whole cells and medium supernatant were determined at various stages of
      incubation. Highest histamine concentrations were detected in the recent
      respiratory isolate; whole cells (225 ng/ml) after 120 h incubation in 15% CO2
      and supernatant (1721 ng/ml) after incubation for 41 h in 25% CO2. This study
      indicates that different H. somnus isolates can produce and secrete histamine
      which may be enhanced by CO2 concentrations which approximate those in the
      bronchial tree. Results of this study may partially explain some of the post
      vaccination reactions occasionally observed with H. somnus bacterins. Additional
      studies are needed to determine the actual role of H. somnus-derived histamine in
      the pathogenesis of bovine respiratory disease and airway hyperresponsiveness.

PMID- 11831744
TI  - An immunochromatographic serological assay for the diagnosis of Mycobacterium
      tuberculosis.
AB  - A rapid serological test for tuberculosis (TB) infection was designed using
      antigens specific to Mycobacterium tuberculosis. Tuberculosis infection, TB
      vaccination and exposure to environmental Mycobacteria cannot be distinguished
      using skin tests based on tuberculin protein derivatives. The standard diagnostic
      techniques such as skin tests, X-rays and DNA techniques are time consuming,
      expensive, and not practical for screening large populations. We used the 38, 63,
      64, 14, 59-kDa antigens of M. tuberculosis to develop a rapid
      immunochromatographic test kit. This study evaluates the diagnostic potential of
      the rapid test kit using TB positive and TB negative serum samples from various
      hospitals in India. The samples were obtained from patients infected with or
      exposed to bacteria and viral pathogens. The results demonstrated that the
      combination of antigens improved the diagnostic specificity and sensitivity. The
      specificity of the test was 99.42% with sensitivity of 98.52% (n = 241). In case
      of multiple infections, the specificity was 93.15% with a low sensitivity of
      73.52% n = 141). The test kit may offer an improved alternative to purified
      protein derivative (PPD). This rapid TB test kit may be a useful tool for first
      line testing of suspected cases, epidemiological studies and in designing a
      quality health system to reduce health hazards in resource-poor countries.

PMID- 11831745
TI  - Vaccination of calves against bovine herpesvirus-1: assessment of the protective
      value of eight vaccines.
AB  - Eight separate, but related experiments, were carried out in which groups of six
      calves were vaccinated with one of eight commercial vaccines. In each experiment
      the vaccinated calves were subsequently exposed to three calves infected with
      virulent bovine herpesvirus-1 (BHV-1). In each experiment, all infected donor
      calves developed a typical severe infectious bovine rhinotracheitis (IBR)
      infection and excreted virus in their nasal secretions of up to 10(8.00)
      TCID50/0.1 ml. One live BHV-1 gE-negative vaccine (A) and three modified live
      vaccines (B, C, D), administered intranasally, all protected against clinical
      disease. The calves vaccinated with one vaccine (C) also did not excrete virus in
      the nasal secretions, whereas the calves protected by vaccines A, B and D
      excreted virus in their nasal secretions but at low titres (10(0.66)-10(1.24)
      TCID50/0.1 ml). A fourth modified live vaccine (E), given intramuscularly, failed
      to prevent mild clinical disease in the calves which also excreted virus in the
      nasal secretions at titre of 10(1.00) TCID50/0.1 ml. An analogous result was
      given by the calves vaccinated with either of the two inactivated vaccines (F and
      G) or with a BHV-1 subunit vaccine (H). All calves developed mild clinical signs
      and excreted virus at titres of 10(2.20)-10(3.12) TCID50/0.1 ml. Calves
      vaccinated with C vaccine were subsequently given dexamethasone, following which
      virus was recovered from their nasal secretions. The virus isolates did not cause
      disease when calves were infected and appeared to be closely related to the
      vaccine strain.

PMID- 11831746
TI  - Isolation and characterization of Mycoplasma arginini from camels (Camelus
      dromedarius) with pneumonia.
AB  - Post-mortem examinations of 100 camels with pneumonic lesions were made at a
      local abattoir for Mycoplasma species. Sixteen isolates with indistinguishable
      biochemical and immunological characters were identified. The biochemical profile
      of these isolates showed that they were sensitive to digitonin, negative for
      urease production, glucose fermentation, and phosphatase activity but were
      positive for arginine hydrolysis. The identity of these isolates was further
      confirmed by disk growth inhibition test using a panel of specific antisera
      against selected reference Mycoplasma spp. Based on the biochemical profile and
      growth inhibition results, the camel isolates were identified as M. arginini. The
      pathological findings associated with M. arginini isolation consisted mostly of
      chronic interstitial pneumonia. The isolation rate of M. arginini from these
      specimens was 8.8%. These results suggest that the role of M. arginini in
      pneumonia in camels should be explored in greater detail.

PMID- 11831747
TI  - Comparative evaluation of indirect and sandwich ELISA for the detection of
      antibodies to bovine respiratory syncytial virus (BRSV) in dairy cattle.
AB  - Seroprevalence of bovine respiratory syncytial virus (BRSV) infection in both
      exotic and crossbred cattle were described. A baculovirus expressed recombinant
      purified nucleocapsid (N) protein was used in indirect and sandwich ELISA for
      screening of 499 bovine sera samples from all over the state for the presence of
      BRSV antibodies. The seroprevalence rate of BRSV was found to be 46.09% through
      indirect ELISA while it would found to be 65.33% by sandwich ELISA. The result
      also indicated that exotic breeds were more susceptible to BRSV infection
      compared to crossbred cattle. A comprehensive analysis on susceptibility to BRSV
      as regards to various factors like age and sex was also summarized.

PMID- 11831748
TI  - Performance and scale-up of adsorptive membrane chromatography.
AB  - Separation efficiency and scalability of Pall Corporation's new Mustang stacked
      membrane chromatographic devices were investigated, using both the 10-ml and l(
      1) models and comparing the responses of tracer pulses obtained for conventional
      and reverse-flow operation. Tracers included AMP, lysozyme, and thyroglobulin,
      which vary in relative molecular mass from less than 1000 up to 650000. Both
      devices showed marked insensitivity to tracer size and flow-rate and gave sharper
      peaks than would have been expected from conventional 15-microm bead packings.
      However, reverse-flow peaks were always significantly sharper than those for
      conventional operation, and the differences were ascribed primarily to non
      uniform header residence times. Numerical simulations of the macroscopic flow
      confirmed that this was indeed the case. This problem was much less pronounced
      for the l(-1) device so scale-up is conservative.

PMID- 11831749
TI  - Set-up of large laboratory-scale chromatographic separations of poly(ethylene
      glycol) derivatives of the growth hormone-releasing factor 1-29 analogue.
AB  - In this paper we report the scale-up of the purification of poly(ethylene glycol)
      (PEG) derivatives of the growth hormone-releasing factor 1-29, from laboratory
      scale (100 mg of bulk starting material) to larger scale (3 g of bulk), through
      the use of a cation-exchange TSK-SP-5PW chromatographic column. A one-step
      purification process capable of purifying large amounts of mono-PEGylated GRF
      species from the crude reaction mixture was developed. A simple, straightforward
      stepwise gradient elution separation was developed at laboratory scale and then
      scaled up with a larger column packed with a chromatographic resin with the same
      chemistry which maintained the laboratory-scale separation profile. Active
      material recovery and material purity remained constant through the scale-up from
      the 13-microm stationary phase to the 25-microm larger column. Overall, the gram
      GRF equivalent/batch process scale showed to be quite reproducible, and could be
      considered as a good platform for scale up to production scale.

PMID- 11831750
TI  - Mass influences in the performance of oligomeric poly(diallyldimethylammonium
      chloride) as displacer for cation-exchange displacement chromatography of
      proteins.
AB  - A novel type of linear polyelectrolyte, namely poly-DADMAC
      [poly(diallyldimethylammonium chloride)], was prepared and studied as a displacer
      for cation-exchange displacement chromatography of proteins. In contrast to the
      commercially available polymers of that chemistry, the novel type of poly-DADMAC
      introduced here is characterized by a homogeneous linear structure, a narrow
      distribution of the (adjustable) molar mass as well as by a defined and
      homogeneous affinity for the stationary phase. Five poly-DADMACs of different
      size (17900 to 88000 g/mol) were prepared and compared with regard to their
      stationary phase affinity and protein separation potential, taking a mixture of
      basic proteins, namely lysozyme, cytochrome C, and ribonuclease A (from bovine
      pancreas), as an example. The steric mass action model was employed to aid method
      development. Under the chosen conditions (low ionic strength of the mobile phase
      guaranteeing strong binding of both the proteins and the displacer) the poly
      DADMAC with the lowest molar masses proved to be the most efficient displacers
      for the basic proteins with a stationary phase affinity constant of 5.3 x 10(16)
      and a steric factor of 224. Using this substance as displacer, a sample mixture
      containing up to three proteins was separated and the proteins recovered at high
      yields (80-97%) and in high purity and concentration.

PMID- 11831751
TI  - Preparative electrophoresis: a general method for the purification of polyclonal
      antibodies.
AB  - Antibodies were purified from normal rabbit, sheep, goat, rat, human and bovine
      serum using preparative electrophoresis on a Gradiflow in a single-step process
      using an asymmetrical cartridge with three different pore size polyacrylamide
      membranes. Recoveries in each case were over 80% and were higher than those
      obtained using affinity chromatography on protein A, protein G or protein L.
      Degree of purity was at least comparable with these methods. These results
      suggest that preparative electrophoresis can be considered a general method for
      the purification of research quantities of antibodies from multiple serum sources
      and may be particularly useful where the reactivity with protein A, G or L is
      unknown.

PMID- 11831752
TI  - Reversed-phase poly(styrene-divinylbenzene) materials optimised for large scale
      preparative and process purification of synthetic peptides and recombinant
      proteins.
AB  - Rigid macroporous copolymers of styrene and divinylbenzene have been designed for
      large-scale preparative and process-scale purification of synthetic peptides and
      recombinant proteins. The polymeric particles are mechanically stable and hence
      able to operate at the required high linear velocities. The pore size and pore
      morphology has been optimised to enable unhindered solute diffusion whilst
      providing maximum available surface area to enhance loading capacity. A 100 A
      pore size has been developed for synthetic peptides and a 300 A pore size for
      recombinant proteins. Precise control of particle size, within the range 10 to 20
      microm, is possible which together with the very narrow particle size
      distribution enables maximum resolution/loading to be obtained within the
      pressure limits of the instrumentation being used. The chemical stability of the
      polymer enables cleaning in place with 1 M sodium hydroxide without particle
      dissolution or a deterioration in selectivity. These materials can be packed into
      compression hardware and are manufactured as single lots up to 100 kg (300 l)
      batch size.

PMID- 11831753
TI  - Use of a modified zirconia support in the separation of immunoproteins.
AB  - Zirconia beads (25-38 microm in diameter) were modified with N,N,N',N'
      ethylenediaminetetramethylenephosphonic acid to generate a zirconia based
      pseudoaffinity support, further referred to as r_PEZ. The influence of pH, salt
      concentration and temperature on the binding of human immunoglobulin G (hIgG) to
      r_PEZ was studied. Temperature had no significant impact on the maximum binding
      capacity (Qmax), and the equilibrium-binding constant (Kd), whereas pH and the
      salt concentration had a noticeable impact on both Qmax and Kd. The Qmax value of
      55 mg hIgG/ml of bead was obtained at a pH of 5.5 and found to decrease with an
      increase of pH. The modified zirconia support allowed the separation of
      immunoglobulins (IgG, IgA and IgM) from untreated human serum. Elution was
      possible under mild conditions with a step salt gradient. Overall protein
      recoveries in the range of 109-125% were obtained with human serum. Human IgG,
      human IgA, and human IgM yields of 29.50+/-6.3, 3.22+/-0.7, and 6.84+/-0.7%,
      respectively, were obtained at a linear velocity of 4.32 cm/min. Purity of
      products, obtained from a single chromatographic step was estimated to be greater
      than 89.0+/-2.6%. The utility of r_PEZ in the selective removal of
      immunoglobulins, as in immunoadsorption was discussed.

PMID- 11831754
TI  - Recovery of antithrombin III from milk by expanded bed chromatography.
AB  - In the present work, a new method of purification for antithrombin was developed
      using an expanded bed chromatography technique. Milk fat was removed by
      centrifugation and caseins were precipitated selectively by addition of zinc
      chloride. Crude skim milk was then directly fed to an expanded bed column
      containing the ion-exchange matrix. The use of a cation-exchanger (P-11) resulted
      in 100% adsorption and 13% recovery whereas the use of an anion-exchanger (DE-52)
      resulted in 100% adsorption and 84% recovery and up to five-fold purification of
      antithrombin. The buffer, 25 mM Tris-HCl pH 8.0; the eluting agent, 2 M
      (NH4)2SO4; and 100% expansion of settled bed were determined to be the optimum
      conditions for the purification of antithrombin by ion-exchange expanded bed
      chromatography. A comparison of column diameters revealed that the elution yields
      increase by two-fold while the column diameter increases from 1 to 2.5 cm.
      However, antithrombin III was concentrated to a higher degree by using the column
      with an internal diameter of 1 cm.

PMID- 11831755
TI  - Comparative study on the fractionation of cellulases on some hydrophobic
      interaction chromatography adsorbents.
AB  - In this work, a comparative study for the fractionation of Trichoderma reesei
      cellulases on five different hydrophobic interaction chromatography adsorbents
      (Butyl-Sepharose 4 FF, Phenyl-Sepharose 6 FF, Octyl-Sepharose 4 FF, Epoxy
      Sepharose CL-6B and Polypropylene glycol-Sepharose CL-6B) is shown. The influence
      of the mobile phase composition on the chromatographic behaviour of T. reesei
      cellulases complex was evaluated using different concentrations of ammonium
      sulphate in the eluent buffer. A selective separation of beta-glucosidase with
      two-fold increase in specific activity and good recoveries of cellobiase activity
      were obtained with Butyl-Sepharose 4 FF and Phenyl-Sepharose 6 FF using 7% (w/v)
      ammonium sulphate in the eluent buffer. A beta-glucosidase fractionation was also
      obtained with Epoxy-Sepharose CL-6B, using 13% (w/v) of the salt in the mobile
      phase.

PMID- 11831756
TI  - Preparative chromatography of xylanase using expanded bed adsorption.
AB  - Expanded bed adsorption was used to purify a marketable xylanase often used in
      the kraft pulp bleaching process. Experiments in packed and expanded beds were
      carried out mainly to study the adsorption of xylanase on to a cationic adsorbent
      (Streamline SP) in the presence of cells. In order to study the presence of
      cells, a Bacillus pumilus mass (5% wet mass) was mixed with the enzyme extract
      and submitted to an expanded bed adsorption system. One xylanase was purified to
      homogeneity in the packed bed. However, the 5% cell content hampered
      purification.

PMID- 11831757
TI  - Separation of binaphthol enantiomers through achiral chromatography.
AB  - Chromatography is a key technique for the analytical, preparative, and production
      scale separation of enantiomers, particularly in the pharmaceutical and fine
      chemicals industries. Although it is common belief that this separation can be
      accomplished only using a chiral stationary phase, it has been recently shown
      that under certain circumstances a non-racemic mixture of specific chiral
      compounds can be separated in two fractions which differ in enantiomeric excess
      (e.e.) also on an achiral stationary phase. In this work we show that in the case
      of the enantiomers of binaphthol in chloroform achiral chromatography on
      LiChrospher 100 NH2 furnishes two fractions constituted of the pure enantiomer
      present in excess and of the racemic mixture, respectively. This is demonstrated
      by on-line monitoring the concentration of both enantiomers at the outlet of a
      chromatographic column fed with a non-racemic pulse of the two enantiomers by
      using a UV detector and a polarimeter in series. Furthermore, we provide
      experimental evidence of the presence of homo- and hetero-dimers in solution
      through NMR experiments and develop a consistent physico-chemical model of the
      solution itself and of the competitive achiral adsorption equilibria. When
      combined with a standard rate model of the chromatographic column this not only
      confirms the possibility of achieving 100% e.e. through achiral chromatography,
      but also allows for a qualitative and quantitative description of all the
      experimentally observed phenomena. Among these, the effect of the enantiomeric
      excess and of the overall concentration of the injected pulse on the
      chromatographic behaviour are worth mentioning.

PMID- 11831758
TI  - Solvent gradient operation of simulated moving beds. I. Linear isotherms.
AB  - The simulated moving bed (SMB) is a multi-column chromatographic separation
      process, which--with respect to the single-column preparative batch process-
      allows for a continuous separation with larger productivity and smaller solvent
      consumption at the same time. The benefits of this process have been shown for
      several different applications in fine chemistry, particularly for the separation
      of enantiomers. In general, SMBs are operated under isocratic conditions.
      However, separation performance can be further improved by applying some sort of
      gradient mode operation, in order to optimize the operating conditions of each
      individual section of the unit. This can be achieved by tuning the retention
      behavior of the solutes to be separated along the unit, namely by enforcing weak
      adsorption conditions in sections 1 and 2, and strong adsorption conditions in
      sections 3 and 4. This can be achieved by applying a temperature gradient (high
      temperature in section 1, and low temperature in section 4), a pressure gradient
      (e.g. in the supercritical SMB, when pressure is high in section 1, and low in
      section 4), or a solvent gradient, which is the aim of this work. In the solvent
      gradient mode the mobile phase consists of a mixture of two or more solvents. To
      different mobile phase compositions corresponds a different retention behavior of
      the solutes, i.e. different adsorption isotherms. In this work we study a closed
      loop SMB unit with solvent mixtures of two different compositions entering the
      unit at the feed and desorbent inlet ports, respectively. Thereby two different
      mobile phase compositions are established in sections 1 and 2, and sections 3 and
      4, respectively. To optimize this process the equilibrium theory design criteria
      for non-linear SMBs are extended to describe this operation mode. It is shown how
      the region of separation is derived and how the optimal operating conditions can
      be found. Finally the solvent gradient mode is compared with the isocratic mode
      in terms of productivity and solvent consumption.

PMID- 11831759
TI  - Scale-up potential of ion-pair high-performance liquid chromatography method to
      produce biologically active inositol phosphates.
AB  - This study was undertaken to evaluate the possibility that an analytical ion-pair
      HPLC procedure used to determine phytic acid (IP6) and its degradation products
      (IP3-IP5) can be transformed to a preparative purification method. A commercial
      phytic acid (CPA) preparation was separated into its component fractions of IP3,
      IP4, IPS, and IP6 on two C18 columns (1.8 and 4.2 ml) using 51% methanol
      containing 0.6-1% tetrabutylammonium hydroxide as ion-pair reagent and 0-0.025 M
      formic acid (pH 4.3) as eluent at 1.7 and 3.0 cm/min linear velocity,
      respectively, and 40 degrees C. Elution was monitored at 40 degrees C by a
      refractive index detector. Reproducible separation of CPA into four well-resolved
      peaks on these columns was possible after optimizing method variables,
      particularly the concentration of ion-pair reagent in the injected sample
      (>1.5%). The same separations were obtained after CPA loads were scaled up 25
      times on a steel column (15 cm x 19 mm I.D.), packed with Ethyl C2 sorbent (10
      microm) and on a 25 cm x 21.2 mm I.D. C18 column, but at a reduced linear
      velocity to increase the resolution. Therefore, this optimization of separation
      not only is useful for analysis of phytic acid and its degradation products but
      also it provides key parameters for scale up for further fractionation and
      characterization.

PMID- 11831760
TI  - Impact of adsorption isotherm parameters on the performance of enantioseparation
      using simulated moving bed chromatography.
AB  - Often there are several chromatographic systems, i.e., combinations of mobile and
      stationary phases, available to solve a certain separation problem. Essential
      differences of these chromatographic systems are the separation factors and the
      efficiencies. For preparative applications in addition also the column saturation
      capacities and solubility limits are of importance. The impact of all these
      parameters appears to be rather well understood for conventional overloaded
      elution chromatography using a single column. In the last years the continuous
      simulated moving bed (SMB) process was increasingly used as a powerful
      alternative to batch elution since increased productivities and reduced solvent
      consumptions could be realised. However, the selection of suitable
      chromatographic systems is more sophisticated for this process. In this paper
      five different chromatographic systems capable of separating the enantiomers of
      mandelic acid are compared based on the achievable productivities using SMB
      chromatography. For these five systems the adsorption isotherms have been
      determined experimentally. Subsequently, an analysis of the SMB process was
      performed numerically using a well-established model.

PMID- 11831761
TI  - Efficient reversed-phase purification of a hydrophobic reaction product following
      Mitsunobu-mediated glycosylation.
AB  - The Mitsunobu reaction was used to attach tetra-O-benzyl-D-glucopyranose to a
      monoindolylmaleimide, providing a key intermediate in the total synthesis of
      indolocarbazole topoisomerase I poisons. Using normal-phase silica gel
      chromatography, purification of the glycosylated product normally required
      multiple columns, resulting in poor recovered yields. Reversed-phase
      chromatography was used successfully to purify this highly hydrophobic material,
      rapidly and in high yield.

PMID- 11831762
TI  - Effect of the homogeneity of the column set on the performance of a simulated
      moving bed unit. II. Experimental study.
AB  - Previous studies of the simulated moving bed (SMB) process assume identical
      characteristics of all the columns incorporated in a given unit. Due to the
      practical impossibility to manufacture identical columns, numerical applications
      of the theory to modeling and optimization use for each of the needed column
      parameter the average value for the entire column set. In this study, the effects
      of these simplifications on the actual productivity of the SMB process are
      evaluated by making exact calculations, i.e., by taking the differences in the
      porosity values into account. We apply a revised set of separation conditions
      previously introduced and derived from the equilibrium theory. Earlier
      theoretical results are compared to experimental results obtained in the study of
      the enantiomeric separation of Troger's base on Chiralpak AD. Due to the
      nonLangmuirian character of the adsorption isotherms of these two compounds on
      the packing material used, the separation area cannot be determined analytically.
      As an alternative, a reliable numerical algorithm was used to scan a wider region
      and to define the separation area. The form of this area depends on the applied
      porosity values. A UV detector and a laser polarimeter located at one node of the
      SMB monitor on-line the internal concentration profiles. Excellent agreement
      between the calculated and the experimentally determined concentration profiles
      was obtained under nonlinear conditions. The influence of column-to-column
      variations on the performance of the SMB process was found to be more significant
      under nonlinear than under linear conditions.

PMID- 11831763
TI  - Characterization of synthetic adsorbents with fine particle sizes for preparative
      scale chromatographic separation.
AB  - Synthetic adsorbents with fine particle sizes (15-30 microm) were manufactured.
      These adsorbents are made of poly(styrenedivinylbenzene) and polymethacrylate,
      and have the same chemical structure as analytical- (5-10 microm) or industrial-
      (200-600 microm) grade synthetic adsorbents. Both of them have very similar
      porous structure to those of analytical or industrial sizes, so that they can
      adsorb compounds of various molecular masses. Chromatographic separation
      characteristics of newly manufactured fine-particle grades of synthetic
      adsorbents were evaluated and compared to those of analytical or industrial
      adsorbents. Reasonable dependency of separation performance on particle size of
      synthetic adsorbents was obtained. Hydraulic properties of fine-grade adsorbents
      had also been measured in view of column operations. Furthermore, scalability and
      applicability of these adsorbents for preparative-scale chromatographic
      separation of bioactive compounds was evaluated. Separation of soybean
      isoflavones and tea catechin derivatives had revealed that fine-grade synthetic
      adsorbents could be well applied with scalability under the same elution
      conditions used for analytical use. Scalability up to a 22400-fold loading amount
      was achieved from a small column packed with analytical-grade adsorbent used for
      method development to a scale-up preparative column packed with fine-grade
      adsorbent used for preparative purification. These results showed the usefulness
      of the fine-grade synthetic adsorbents for more precise purification of bioactive
      compounds, including pharmaceuticals and functional food additives with higher
      recovery.

PMID- 11831764
TI  - Characterization of enthalpic events in overloaded ion-exchange chromatography.
AB  - Protein adsorption can be either endothermic or exothermic depending upon the
      protein, the sorbent and process conditions. In the case of protein adsorption
      onto ion-exchange surfaces exothermic adsorption heats are usually characterized
      as representing the electrostatic interaction between two oppositely charged
      surfaces. Endothermic adsorption heats are typically characterized as
      representing protein reconfiguration and/or repulsive interactions between
      adsorbed molecules. In certain segments of the literature surface dehydration and
      solution non-idealities have been suggested as possible sources of endothermic
      heats of adsorption. Each of these phenomena was investigated during studies
      concerning the adsorption of bovine serum albumin and ovalbumin onto an anion
      exchange sorbent. The results demonstrated that electrostatic repulsive
      interactions between adsorbed molecules appears to be a larger contributor to
      endothermic heats of adsorption than surface dehydration or solution non
      idealities. The presence of mobile phase cations can reduce the magnitude of
      endothermic adsorption heats by screening repulsive interactions between adsorbed
      molecules. Although water release was not found to be a major contributor to
      endothermic adsorption heats, it is likely to be a contributor to the entropic
      driving force associated with the adsorption of bovine serum albumin.

PMID- 11831765
TI  - Maintenance of column performance at scale.
AB  - Pack-in-place column packing methods were developed for Q Sepharose Big Beads at
      40 cm I.D. and scaled up to 200 cm I.D. in Chromaflow columns. The efficiency and
      asymmetry of the packed bed were evaluated as a function of test velocity and
      sample volume. The performance of the packed beds at both scales approached the
      theoretical limits of column performance (Hred =2 and Af=1) expected in small
      analytical columns. The packing strategy was effective for scale up and the
      stability of the packed beds, the effectiveness of the column design with respect
      to the mobile phase distribution system and the stability of the media to the
      pack-in-place technology, are presented.

PMID- 11831766
TI  - Two-step solvent gradients in simulated moving bed chromatography. Numerical
      study for linear equilibria.
AB  - The application of gradients in simulated moving bed (SMB) chromatography has
      recently attracted interest as a method for further improving the performance of
      this continuous separation process. One possible implementation of gradients
      consists in setting the solvent strength in the desorbent stream higher than that
      in the feed stream. As a result, the components to be separated are more retained
      in the zones upstream of the feed position and more easily eluted in the zones
      downstream of the feed position. If a liquid mobile phase is used, gradients can
      be created by dosing different solvents into the feed and desorbent ports. In a
      closed-loop gradient SMB arrangement the solvent strength within the unit will
      depend on the two feed compositions and on the characteristic flow-rates of the
      process. In this work an equilibrium stage model describing a true moving bed
      process is used to analyze numerically the main features of a two-step gradient
      SMB process. The adsorption isotherms are assumed to be always linear under
      isocratic conditions. The relevant Henry constants depend in a nonlinear manner
      on the composition of the solvent. Based on numerical simulations the impact of
      the two inlet solvent compositions is demonstrated in terms of the size and shape
      of regions of applicable flow-rates. Different strategies of designing the
      process are discussed and compared with respect to maximizing productivities and
      minimizing desorbent requirements.

PMID- 11831767
TI  - Optimal design of batch and simulated moving bed chromatographic separation
      processes.
AB  - Preparative chromatography, especially simulated moving bed (SMB) chromatography,
      is a key technology for the separation of fine chemicals on a production scale.
      Most of the design methods for batch and SMB processes proposed in the open
      literature deal with the optimisation of the operating conditions for a given
      chromatographic unit only. Therefore, a comparison of the process economy may
      lead to incorrect results. In this contribution, an effective strategy for the
      optimal choice of all process parameters (operation and design parameters) is
      proposed. The main idea of this strategy is to apply a detailed and
      experimentally validated process model and to reduce the number of influencing
      parameters by introducing and optimising dimensionless process parameters. It is
      shown that there is an infinite choice of design and operating parameters to
      achieve maximum productivity or minimum separation costs and not at the maximum
      pressure drop only. The detailed design of the chromatographic unit and the
      selection of the operating conditions can be adjusted by considering the
      availability of columns and packing materials. As the model system, the
      separation of a racemic mixture (EMD53986) on Chiralpak AD was investigated.
      After complete optimisation of a batch and a SMB unit, a real comparison of the
      process economy can be achieved. Finally, the influences of two different
      objective functions, productivity and specific separation cost, are analysed.

PMID- 11831768
TI  - Development of an Acanthamoeba-specific reverse dot-blot and the discovery of a
      new ribotype.
AB  - Acanthamoeba is a genus of free-living amoebae, of which some species have been
      found to cause opportunistic infections in humans. The identification of these
      amoebae in natural and disease samples is based primarily upon morphological
      features. While these features are more than adequate for identification to the
      genus level, they are not useful for species-level identification. This not only
      leads to difficulty in the diagnosis of infections, but it makes an accurate
      assessment of the natural distribution of acanthamoebae very difficult to
      achieve. To improve this situation, a detection method was developed that
      utilizes both selective polymerase chain reaction amplification and the reverse
      dot-blot. Oligonucleotides were designed to be specific for the described
      ribosomal groups (or ribotypes) of Acanthamoeba, as well as one specific for the
      genus itself. When this method was used to analyze a series of Acanthamoeba
      cultures from Pakistan, a new ribotype was identified in addition to the
      detection of the ubiquitously distributed T4 type.

PMID- 11831769
TI  - Correlation between in vitro and in vivo infectivity of Leishmania infantum
      clones.
AB  - Eleven clones of a single strain of Leishmania infantum (MCAN/ES/88/ISS441, Doba)
      were analyzed for biological behavior in vivo and in vitro. Different clones
      showed differences in growth dependent upon the two culture media employed. All
      clones displayed only slight differences in H2O2 and NaNO2 sensitivity compared
      to the original strain, whereas in vitro infectivity for mouse peritoneal
      macrophages differed significantly among the clones. In vivo infections in
      hamsters correlated strongly with in vitro infectivity. The phenotypic
      differences found suggest a polyclonal structure for the Leishmania infantum
      strain studied.

PMID- 11831770
TI  - Spore ornamentation of Haplosporidium pickfordi Barrow, 1961 (Haplosporidia), a
      parasite of freshwater snails in Michigan, USA.
AB  - Spore ornamentation is increasingly recognized as a key character for species
      differentiation and genus assignment in the phylum Haplosporidia. Unfortunately,
      spore ornamentation is known for only a small number of described species so it
      is difficult to assign most species to genera with any confidence. Scanning and
      transmission electron microscopy were used to determine the presence and
      morphology of spore ornamentation of Haplosporidium pickfordi collected from the
      digestive gland of the snail Physella parkeri in Douglas Lake, Michigan. Spores
      possess filaments that are derived from the spore wall and originate from two
      separate areas at the posterior end of the spore. When spores are first isolated
      from host tissue, filaments are fused into a sheet that wraps around the spore,
      passing under the opercular lid. These filaments gradually unravel when spores
      are held in water and after about 14 d most filaments project freely from the
      posterior end of the spore. The number of filaments could not be determined with
      certainty, but appears to be approximately nine. Filaments are 100 nm in diam.
      and up to 50 microm in length. The presence of spore wall-derived filaments
      confirms the placement of the parasite in the genus Haplosporidium.

PMID- 11831771
TI  - Leptotheca sparidarum n. sp. (Myxosporea: Bivalvulida), a parasite from cultured
      common dentex (Dentex dentex L.) and gilthead sea bream (Sparus aurata L.)
      (Teleostei: Sparidae).
AB  - A new myxosporean, Leptotheca sparidarum n. sp., is described from the trunk
      kidney of two sparid fish, Sparus aurata and Dentex dentex, in several culture
      facilities from the Western Mediterranean coasts. It is distinguished from all
      the previously described species by spore morphometrics. Spores with two equal
      polar capsules and one binucleated sporoplasm. Spore measurements from D. dentex
      were 5-7.1 micron long x 8.8-12.3 micron thick x 5.88-6.18 micron wide; polar
      capsules 2.6-3.5 micron in diam. Spore measurements from S. aurata were 5.1-8.24
      micron long x 9.41-11.76 micron thick; polar capsules 2.4-3.2 micron in diam. No
      significant differences were detected between either host. Prevalence could reach
      21.4% in D. dentex and 19% in some stock of S. aurata. Renal tubules were the
      typical site of infection, which was also found in ureters and glomeruli, but
      seldom in the epiepithelial position of the gut. Spores were formed in disporous
      sporoblasts, and spore maturation seemed to proceed from the host epithelium
      towards the lumen. Trophozoites were attached to the host epithelial cells of
      renal tubules by pseudopodial-like projections, which were inserted into gaps
      between epithelial cells. Also, cell junctions were observed between primary
      cells and between neighboring spores.

PMID- 11831772
TI  - Phagosome formation in Paramecium: roles of somatic and oral cilia and of solid
      particles as revealed by video microscopy.
AB  - The roles of somatic and oral cilia and solid particles during digestive vacuole
      (DV) formation in Paramecium multimicronucleatum were investigated using video
      enhanced and immunofluorescence microscopy. Membrane incorporation into DVs was
      found to increase linearly with increasing particle concentration. The rate of
      discoidal vesicle transport to the cytopharynx was not affected by particles,
      showing that particles are not required for membrane trafficking to the
      cytopharynx. However, the presence of particles leads to an increased membrane
      fusion between the cytopharyngeal membrane and the discoidal vesicles. When live
      cells lost their somatic cilia on the left-ventral side anterior to the oral
      region due to deciliation, membrane incorporation into newly formed DVs was
      strongly inhibited. Using video-enhanced microscopy, latex beads were seen to be
      loaded along the quadrulus on the dorsal surface of the buccal cavity, but few
      beads were seen next to the dorsal and ventral peniculi. Particle sequestration
      into a pre-formed nascent digestive vacuole (NDV) was studied in Triton X-100
      permeabilized cells whose ciliary beating was reactivated by the addition of Mg
      ATP. Both beat frequency and the percentage of cells containing bead-labeled NDV
      were dependent on the Mg-ATP concentration: the higher the beat frequency, the
      higher the percentage of cells with a bead-labeled NDV. These results suggest
      that ciliary beating is probably the only mechanism required for particle
      accumulation in the NDV, while a coordinated beating of the somatic cilia on the
      left-ventral side anterior to the oral region as well as the quadrulus moves
      particles into the NDV. The beating of the peniculi may somehow prevent the
      backward flow of particles out of the NDV.

PMID- 11831773
TI  - Tubulins in Trichomonas vaginalis: molecular characterization of alpha-tubulin
      genes, posttranslational modifications, and homology modeling of the tubulin
      dimer.
AB  - We have isolated and analysed an alpha-tubulin-encoding gene (atub1) in an early
      diverging eukaryote, Trichomonas vaginalis. The complete atub1 open reading frame
      included 1.356 bp encoding a polypeptide of 452 amino-acyl residues. A second
      alpha-tubulin gene (atub2) was amplified by PCR using primers derived from
      consensus alpha-tubulin amino acid sequences. Both T. vaginalis alpha-tubulin
      sequences showed high identity to those described in other parabasalids (94.4%
      97.3%), and exhibited a high degree of similarity to sequences from Metazoa (such
      as pig brain) and diplomonads (such as Giardia). Despite large evolutionary
      distances previously observed between trichomonads and mammals, the three
      dimensional model of the T. vaginalis tubulin dimer was very similar to that of
      pig brain. Possible correlations between alpha-tubulin sequences and
      posttranslational modifications (PTMs) were examined. Our observations
      corroborated previous data obtained in T. vaginalis using specific anti-PTMs
      antibodies. As described in the related species Tritrichomonas mobilensis,
      microtubules are likely acetylated, non-tyrosinated, glutamylated, and non
      glycylated in T. vaginalis. Evolutionary considerations concerning the time of
      appearance of these tubulin PTMs are also discussed since trichomonads are
      potentially one of the earliest diverging eukaryotic lineages.

PMID- 11831774
TI  - Korotnevella hemistylolepis n. sp. and Korotnevella monacantholepis n. sp.
      (Paramoebidae), two new scale-covered mesohaline amoebae.
AB  - Two new species of Korotnevella Goodkov, 1988, Korotnevella hemistylolepis n. sp.
      and Korotnevella monacantholepis n. sp., are described from mesohaline
      ecosystems. The amoebae are characterized on the basis of light and electron
      microscopy with special emphasis on the structure of the basket scales, which
      have species-specific architecture. The two new species are the second and third
      ones recovered from environments other than freshwater. In terms of scale
      morphology they most closely resemble a freshwater species, Korotnevella bulla
      (Schaeffer, 1926) Goodkov, 1988. Two genus names, Dactylamoeba Korotnev, 1880 and
      Korotnevella Goodkov, 1988, are in current use. The latter name is preferred,
      pending rediscovery and characterization of Dactylamoeba elongata Korotnev, 1880,
      the type species of the genus. Korotnevella species can be divided into three
      groups on the basis of scale morphology, suggesting that the genus may not be
      monophyletic. A key to species is provided.

PMID- 11831775
TI  - Platyamoeba pseudovannellida n. sp., a naked amoeba with wide salt tolerance
      isolated from the Salton Sea, California.
AB  - A new species of naked amoeba, Platyamoeba pseudovannellida n.sp., is described
      on the basis of light microscopic and fine structural features. The amoeba was
      isolated from the Salton Sea, California, from water at a salinity of ca. 44%.
      Locomotive amoebae occasionally had a spatulate outline and floating cells had
      radiating pseudopodia, sometimes with pointed tips. Both these features are
      reminiscent of the genus Vannella. However, the surface coat (glycocalyx) as
      revealed by TEM indicates that this is a species of Platyamoeba. Although
      salinity was not used as a diagnostic feature, this species was found to have
      remarkable tolerance to fluctuating salinity levels, even when changes were
      rapid. Amoebae survived over the range 0 per thousand to 150 per thousand salt
      and grew within the range 0 per thousand to 138 per thousand salt. The generation
      time of cells averaged 29 h and was not markedly affected by salt concentration.
      This is longer than expected for an amoeba of this size and suggests a high
      energetic cost of coping with salinity changes. The morphology of cells changed
      with increasing salinity: at 0 per thousand cells were flattened and active and
      at the other extreme (138 per thousand) amoebae were wrinkled and domed and cell
      movement was very slow. At the ultrastructural level, the cytoplasm of cells
      grown at high salinity (98 per thousand was considerably denser than that of
      cells reared at 0 per thousand.

PMID- 11831776
TI  - FISH probes for the detection of the parasitic dinoflagellate Amoebophrya sp.
      infecting the dinoflagellate Akashiwo sanguinea in Chesapeake Bay.
AB  - A comparison of the small subunit rRNA sequences of a Chesapeake Bay strain of
      the dinoflagellate Akashiwo sanguinea and the dinoflagellate Amoebophrya sp.
      parasitizing it revealed several potential target sites that could be used to
      detect the parasite through in situ hybridization. The fluorescence of probed
      cells under various conditions of hybridization was measured by using a spot
      meter on a Nikon UFX-II camera attachment so that the effect of various
      hybridization parameters on probe binding could be determined. Probes directed
      against both the junction between helices 8 and 11 and helix 46 could detect the
      parasite, although the helix 8/11 probe produced a stronger signal under the
      conditions tested. The fluorescence of the probed cells increased with increasing
      hybridization time up to approximately twelve hours. The background fluorescence
      was lower at the wavelengths used to detect Texas Red than at those used to
      detect fluorescein, so probed cells were more distinct when Texas Red was used as
      the label. Cells stored in cold paraformaldehyde for a year still bound the
      probes. Young stages of the parasite could be seen more readily after in situ
      hybridization than after protargol impregnation.

PMID- 11831778
TI  - Odd mating-type substances may work as precursor molecules of even mating-type
      substances in Paramecium caudatum.
AB  - Mating-type substances are key molecules in the sexual recognition of the odd (O)
      and even (E) complementary mating-type cells in Paramecium caudatum. Indirect
      evidence suggested that the substances were proteins and were located on ventral
      surface cilia. Monoclonal antibodies inhibiting the mating reactivity of the O
      cells have been obtained. Using these antibodies, we tried to detect antigen
      molecules as dot-blot signals. Strong dot-blot signals of antigens were only
      detected from the mating reactive cells, but they were not detected from the well
      fed and starved cells without mating reactivity. In addition to identifying the
      antigen on cilia and cytoplasm of the O cell, the antigen was detected from the
      cytoplasm of the E cells but never from their cilia. Furthermore, extracts of the
      E cells induced mating reaction with the living E cells but not with O cells.
      Thus, the O mating-type substances exist in the cytoplasm of the E mating-type
      cells, supporting strongly the hypothesis that O mating-type substances are
      precursor molecules of the E mating-type substances.

PMID- 11831777
TI  - Isolation of a unique membrane protein from Naegleria fowleri.
AB  - Naegleria fowleri, an amoeboflagellate, is the causative agent of Primary Amoebic
      Meningoencephalitis, a fulminating disease of the central nervous system. In
      order to elucidate the mechanisms of pathogenicity of this amoeba, a cDNA
      expression library was prepared from N. fowleri RNA. A specific protein was found
      to be expressed from a cDNA clone designated Mp2CL5. Northern blot analysis
      showed that the Mp2CL5 mRNA was expressed in pathogenic N. fowleri but was not
      expressed in non-pathogenic Naegleria species nor in Acanthamoeba. Western blot
      analysis using anti-N. fowleri antiserum demonstrated that IPTG-induced
      Escherichia coli Mp2CL5 expressed a 23-kDa recombinant protein. The Mp2CL5
      recombinant protein was histidine-tagged and purified to homogeneity from E.
      coli. A polyclonal rabbit antiserum was prepared against the purified Mp2CL5
      recombinant protein. This antibody was used to further characterize the Mp2CL5
      native protein expressed by N. fowleri. Western blot analysis in conjunction with
      immunofluorescence microscopy demonstrated the presence of a native protein of 17
      kDa on the plasma membrane of N. fowleri trophozoites. The native N. fowleri
      protein was expressed in the logarithmic phase of trophozoite growth and the
      production of this protein increased through the stationary phase of growth.
      Studies are in progress to examine further its role as a virulence factor.

PMID- 11831779
TI  - Nuclear and cortical regulation in doublets of Paramecium: II. When and how do
      two cortical domains reorganize to one?
AB  - Homopolar doublets with twofold rotational symmetry were generated in Paramecium
      tetraurelia and in P. undecaurelia by electrofusion or by arrested conjugation.
      These doublets underwent a complex cortical reorganization over time, which led
      to their reversion to singlets. This reorganization involved a reduction in
      number of ciliary rows, a progressive inactivation and loss of one oral meridian,
      and a reduction and eventual disappearance of one cortical surface (semicell)
      situated between the two oral meridians. The intermediate steps of this
      reorganization included some processes that resemble those previously described
      in regulating doublets of other ciliates, and others that are peculiar to members
      of the "P. aurelia" species-group and some of its close relatives. The former
      included a disappearance of one cortical landmark (a contractile vacuole
      meridian) and transient appearance of another (a third cytoproct) within the
      narrower semicell. The latter included a reorganization of the paratene zone and
      the associated invariant (non-duplicating) region to occupy the entire narrower
      semicell and a redistribution of zones of most active basal-body proliferation
      within the opposite, wider semicell. The final steps of reorganization involved
      anterior displacement, invagination, and resorption of one of the two oral
      apparatuses and eventual disappearance of the associated oral meridian. An oral
      meridian deprived of its oral apparatus, either by spontaneous resorption or
      microsurgical removal, could persist for some time in "incomplete doublets"
      before regulating to the singlet condition. The phylogenetically widespread
      events encountered in the regulation of doublets to singlets suggest that
      Paramecium shares some of the global regulatory properties that are likely to be
      ancestral in ciliates. The more specific events are probably associated with the
      complex cytoskeletal architecture of this organism and with the frequent
      occurrence of autogamy that was described in the preceding study (Prajer et al.
      1999).

PMID- 11831780
TI  - Molecular cloning and characterization of a gene encoding a 13.1 kDa antigenic
      protein of Naegleria fowleri.
AB  - An antigen-related gene was cloned from a cDNA expression library of Naegleria
      fowleri by immunoscreening with sera obtained from mice that were either
      immunized with an amoebic lysate or infected with trophozoites. The coding
      nucleotide sequence of the cloned gene consisted of 357 bases that were
      translated into 119 amino acids. This gene was designated as nfa1. The predicted
      amino acid sequence of Nfa1 protein has two potential glycosylation and three
      potential phosphorylation sites, and its predicted secondary structure consists
      of four helices and three corners. The deduced amino acid sequence of Nfa1
      protein shares 43% identity with the myohemerythrin (myoHr) protein from a marine
      annelid, Nereis diversicolor, including 100% identity in conserved regions and
      iron-binding residues. A phylogenetic tree constructed from amino acid sequences
      placed the N. fowleri Nfa1 protein outside of a cluster of myoHr proteins from
      eight invertebrates. A purified recombinant protein that migrated as a 13.1 kDa
      species in SDS-PAGE was produced. This recombinant protein exhibited a strong
      immunoreactivity with infected, immune, and anti-Nfal sera. In addition, an anti
      Nfa1 serum reacted with an amoeba lysate in immunoblotting analysis. The present
      nfal gene encoding the myoHr-like protein is the first myoHr gene cloned from
      protozoa, and the Nfal antigen may be useful in diagnostic studies

PMID- 11831781
TI  - Stability of functional equivalence and stimulus equivalence: effects of baseline
      reversals.
AB  - Functional equivalence and stimulus equivalence classes were established,
      reversed, and tested for stability with college students. Functional stimulus
      classes were established using a task in which students were trained to say
      nonsense words in the presence of arbitrarily assigned sets of symbols. Computer
      controlled speech-recognition technology was used to record and analyze students'
      vocal responses for accuracy. After the establishment of stimulus classes was
      demonstrated with a transfer-of-function test, the effects of reversing selected
      baseline simple discriminations were assessed during an additional transfer-of
      function test and a follow-up test that occurred several weeks later. With the
      same students, stimulus equivalence classes were established and demonstrated
      with computerized matching-to-sample procedures. The effects of reversing
      selected baseline conditional discriminations also were assessed during a
      postreversal equivalence test and a follow-up test. Both functional stimulus
      classes and stimulus equivalence were sensitive to contingency reversals, but the
      reversals with stimulus equivalence closses affected stimulus class organization
      whereas reversals with functional stimulus classes did not. Follow-up
      performances were largely consistent with the original baseline contingencies.
      The similarities and differences between stimulus equivalence and functional
      equivalence are related to the specific contingencies that select responding in
      the presence of the stimuli that form the classes.

PMID- 11831782
TI  - Linear modeling of steady-state behavioral dynamics.
AB  - The observed steady-state behavioral dynamics supported by unsignaled periods of
      reinforcement within repeating 2,000-s trials were modeled with a linear transfer
      function. These experiments employed improved schedule forms and analytical
      methods to improve the precision of the measured transfer function, compared to
      previous work. The refinements include both the use of multiple reinforcement
      periods that improve spectral coverage and averaging of independently determined
      transfer functions. A linear analysis was then used to predict behavior observed
      for three different test schedules. The fidelity of these predictions was
      determined.

PMID- 11831784
TI  - Choice in a variable environment: effects of blackout duration and extinction
      between components.
AB  - Pigeons were trained in a procedure in which sessions included seven four- or 10
      reinforcer components, each providing a different reinforcer ratio that ranged
      from 27:1 to 1:27. The components were arranged in random order, and no signals
      differentiated the component reinforcer ratios. Each condition lasted 50
      sessions, and the data from the last 35 sessions were analyzed. Previous results
      using 10-s blackouts between components showed some carryover of preference from
      one component to the next, and this effect was investigated in Experiment 1 by
      varying blackout duration from 1 s to 120 s. The amount of carryover decreased
      monotonically as the blackout duration was lengthened. Preference also decreased
      between reinforcers within components, suggesting that preference change during
      blackout might follow the same function as preference change between reinforcers.
      Experiment 2 was designed to measure preference change between components more
      directly and to relate this to preference change during blackout. In two
      conditions a 60-s blackout occurred between components, and in two other
      conditions a 60-s period of unsignaled extinction occurred between components.
      Preference during the extinction period progressively fell toward indifference,
      and the level of preference following extinction was much the same as that
      following blackout. Although these results are consistent with Davison and Baum's
      (2000) theory of the effects of reinforcers on local preference, other findings
      suggest that theory is incomplete: After a sequence of reinforcers from one
      alternative, some residual preference remained after 60 s of extinction or
      blackout, indicating the possibility of an additional longer term accumulation of
      reinforcer effects than originally suggested.

PMID- 11831783
TI  - Relative reinforcing effects of different oral ethanol doses in rhesus monkeys.
AB  - The relative reinforcing effects of different doses of orally delivered ethanol
      were evaluated. Mouth-contact responding by rhesus monkeys was measured under
      concurrent fixed-ratio fixed-ratio schedules of liquid delivery (0.67
      ml/delivery) from each of two spouts during daily 3-hr sessions. Experiment 1
      examined persistence of responding with ethanol (2%, 8%, and 32% wt/vol) and
      water available. When fixed-ratio values from 8 to 128 were tested, the number of
      ethanol deliveries obtained per session decreased as the response requirement
      increased. The decrease in deliveries was less at higher than at lower ethanol
      concentrations, however. Experiment 2 examined choice between two ethanol
      concentrations under concurrent fixed-ratio 16 schedules (4% vs. 8%, 4% vs. 16%,
      8% vs. 16%, 2% vs. 8%, 2% vs. 32%, 8% vs. 32%). Higher concentrations (16%, 32%)
      generally maintained more responding than concurrently available concentrations
      of 8% or less. An exception was the observation of a preference for 8% over 32%
      ethanol. When the fixed-ratio value was increased, however, the relative
      preference for these two doses was reversed so that 32% ethanol maintained more
      responding than 8% ethanol. Thus, the direction of the preference depended on the
      size of the response requirement. These results indicate that the reinforcing
      effects of ethanol increase with dose.

PMID- 11831786
TI  - Locating far-field impulsive sound sources in air by triangulation.
AB  - The firing of a gun generates an acoustic impulse that propagates radially
      outwards from the source. Acoustic gun-ranging systems estimate the source
      position by measuring the relative time of arrival of the impulse at a number of
      spatially distributed acoustic sensors. The sound-ranging problem is revisited
      here using improved time-delay estimation methods to refine the source position
      estimates. The time difference for the acoustic wavefront to arrive at two
      spatially separated sensors is estimated by cross correlating the digitized
      outputs of the sensors. The time-delay estimate is used to calculate the source
      bearing, and the source position is cross fixed by triangulation using the
      bearings from two widely separated receiving nodes. The variability in the
      bearing and position estimates is quantified by processing acoustic sensor data
      recorded during field experiments for a variety of impulsive sound sources:
      artillery guns, mortars, and grenades. Imperfect knowledge of the effective speed
      of sound travel results in bias errors in the source bearing estimates, which are
      found to depend on the orientation of the sensor pair axis with respect to the
      source direction. Combining the time-delay estimates from two orthogonal pairs of
      sensors reduces these bias errors.

PMID- 11831787
TI  - Passive ranging errors due to multipath distortion of deterministic transient
      signals with application to the localization of small arms fire.
AB  - A passive ranging technique based on wavefront curvature is used to estimate the
      ranges and bearings of impulsive sound sources represented by small arms fire.
      The discharge of a firearm results in the generation of a transient acoustic
      signal whose energy propagates radially outwards from the omnidirectional source.
      The radius of curvature of the spherical wavefront at any instant is equal to the
      instantaneous range from the source. The curvature of the acoustic wavefront is
      sensed with a three-microphone linear array by first estimating the differential
      time of arrival (or time delay) of the acoustic wavefront at each of the two
      adjacent sensor pairs and then processing the time-delay information to extract
      the range and bearing of the source. However, modeling the passive ranging
      performance of the wavefront curvature method for a deterministic transient
      signal source in a multipath environment shows that when the multipath and direct
      path arrivals are unresolvable, the time-delay estimates are biased which, in
      turn, biases the range estimates. The model explains the observed under-ranging
      of small arms firing positions during a field experiment.

PMID- 11831785
TI  - Drug discrimination under concurrent variable-ratio variable-ratio schedules.
AB  - Pigeons were trained to discriminate 5 mg/kg pentobarbital from saline under
      concurrent variable-ratio (VR) VR schedules, in which responses on the
      pentobarbital-biased lever were reinforced under the VR schedule with the smaller
      response requirements when pentobarbital was given before the session, and
      responses on the saline-biased key were reinforced under the VR schedule with the
      larger response requirements. When saline was administered before the session,
      the reinforcement contingencies associated with the two response keys were
      reversed. When responding stabilized under concurrent VR 20 VR 30, concurrent VR
      10 VR 40, or concurrent VR 5 VR 50 schedules, pigeons responded almost
      exclusively on the key on which fewer responses were required to produce the
      reinforcer. When other doses of pentobarbital and other drugs were substituted
      for the training dose, low doses of all drugs produced responding on the saline
      biased key. Higher doses of pentobarbital and chlordiazepoxide produced
      responding only on the pentobarbital-biased key, whereas higher doses of ethanol
      and phencyclidine produced responding only on this key less often. d-Amphetamine
      produced responding primarily on the saline-biased key. When drugs generalized to
      pentobarbital, the shape of the generalization curve under concurrent VR VR
      schedules was more often graded than quantal in shape. Thus, drug discrimination
      can be established under concurrent VR VR schedules, but the shapes of drug
      discrimination dose-response curves under concurrent VR VR schedules more closely
      resemble those seen under interval schedules than those seen under fixed-ratio
      schedules. Graded dose-response curves under concurrent VR VR schedules may
      relate to probability matching and difficulty in discriminating differences in
      reinforcement frequency.

PMID- 11831788
TI  - Quantifying uncertainty in geoacoustic inversion. I. A fast Gibbs sampler
      approach.
AB  - This paper develops a new approach to estimating seabed geoacoustic properties
      and their uncertainties based on a Bayesian formulation of matched-field
      inversion. In Bayesian inversion, the solution is characterized by its posterior
      probability density (PPD), which combines prior information about the model with
      information from an observed data set. To interpret the multi-dimensional PPD
      requires calculation of its moments, such as the mean, covariance, and marginal
      distributions, which provide parameter estimates and uncertainties. Computation
      of these moments involves estimating multi-dimensional integrals of the PPD,
      which is typically carried out using a sampling procedure. Important goals for an
      effective Bayesian algorithm are to obtain efficient, unbiased sampling of these
      moments, and to verify convergence of the sample. This is accomplished here using
      a Gibbs sampler (GS) approach based on the Metropolis algorithm, which also forms
      the basis for simulated annealing (SA). Although GS can be computationally slow
      in its basic form, just as modifications to SA have produced much faster
      optimization algorithms, the GS is modified here to produce an efficient
      algorithm referred to as the fast Gibbs sampler (FGS). An automated convergence
      criterion is employed based on monitoring the difference between two independent
      FGS samples collected in parallel. Comparison of FGS, GS, and Monte Carlo
      integration for noisy synthetic benchmark test cases indicates that FGS provides
      rigorous estimates of PPD moments while requiring orders of magnitude less
      computation time.

PMID- 11831789
TI  - Quantifying uncertainty in geoacoustic inversion. II. Application to broadband,
      shallow-water data.
AB  - This paper applies the new method of fast Gibbs sampling (FGS) to estimate the
      uncertainties of seabed geoacoustic parameters in a broadband, shallow-water
      acoustic survey, with the goal of interpreting the survey results and validating
      the method for experimental data. FGS applies a Bayesian approach to geoacoustic
      inversion based on sampling the posterior probability density to estimate
      marginal probability distributions and parameter covariances. This requires
      knowledge of the statistical distribution of the data errors, including both
      measurement and theory errors, which is generally not available. Invoking the
      simplifying assumption of independent, identically distributed Gaussian errors
      allows a maximum-likelihood estimate of the data variance and leads to a
      practical inversion algorithm. However, it is necessary to validate these
      assumptions, i.e., to verify that the parameter uncertainties obtained represent
      meaningful estimates. To this end, FGS is applied to a geoacoustic experiment
      carried out at a site off the west coast of Italy where previous acoustic and
      geophysical studies have been performed. The parameter uncertainties estimated
      via FGS are validated by comparison with: (i) the variability in the results of
      inverting multiple independent data sets collected during the experiment; (ii)
      the results of FGS inversion of synthetic test cases designed to simulate the
      experiment and data errors; and (iii) the available geophysical ground truth.
      Comparisons are carried out for a number of different source bandwidths, ranges,
      and levels of prior information, and indicate that FGS provides reliable and
      stable uncertainty estimates for the geoacoustic inverse problem.

PMID- 11831790
TI  - An energy-conserving one-way coupled mode propagation model.
AB  - The equations of motion for pressure and displacement fields in a waveguide have
      been used to derive an energy-conserving, one-way coupled mode propagation model.
      This model has three important properties: First, since it is based on the
      equations of motion, rather than the wave equation, instead of two coupling
      matrices, it only contains one coupling matrix. Second, the resulting coupling
      matrix is anti-symmetric, which implies that the energy among modes is conserved.
      Third, the coupling matrix can be computed using the local modes and their depth
      derivatives. The model has been applied to two range-dependent cases: Propagation
      in a wedge, where range dependence is due to variations in water depth and
      propagation through internal waves, where range dependence is due to variations
      in water sound speed. In both cases the solutions are compared with those
      obtained from the parabolic equation (PE) method.

PMID- 11831791
TI  - Effective medium approach to linear acoustics in bubbly liquids.
AB  - Linear wave propagation through a bubbly liquid has seen a resurgence of interest
      because of proposed "corrections" to the lowest-order approximation of an
      effective wave number obtained from Foldy's exact multiple scattering theory
      [Foldy, Phys. Rev. 67, 107 (1945)]. An alternative approach to wave propagation
      through a bubbly liquid reduces the governing equations for a two-phase medium to
      an effective medium. Based on this approach, Commander and Prosperetti [J.
      Acoust. Soc. Am. 85, 732 (1989)] derive an expression for the lowest-order
      approximation to an effective wave number. At this level of approximation the
      bubbles interact with only the mean acoustic field without higher-order
      rescattering. That is, the field scattered from a bubble may interact with one or
      more new bubbles in the distribution, but a portion of that scattered field may
      not be scattered back to any previous bubble. The current article shows that
      modifications to the results of Commander and Prosperetti lead to a new
      expression for the effective wave number, which properly accounts for all higher
      orders of multiple scattering.

PMID- 11831792
TI  - Development of an acoustic actuator for launch vehicle noise reduction.
AB  - In many active noise control applications, it is necessary that acoustic
      actuators be mounted in small enclosures due to volume constraints and in order
      to remain unobtrusive. However, the air spring of the enclosure is detrimental to
      the low-frequency performance of the actuator. For launch vehicle noise control
      applications, mass and volume constraints are very limiting, but the low
      frequency performance of the actuator is critical. This work presents a novel
      approach that uses a nonlinear buckling suspension system and partial evacuation
      of the air within the enclosure to yield a compact, sealed acoustic driver that
      exhibits a very low natural frequency. Linear models of the device are presented
      and numerical simulations are given to illustrate the advantages of this design
      concept. An experimental prototype was built and measurements indicate that this
      design can significantly improve the low-frequency response of compact acoustic
      actuators.

PMID- 11831793
TI  - Active control of road booming noise in automotive interiors.
AB  - An active feedforward control system has been developed to reduce the road
      booming noise that has strong nonlinear characteristics. Four acceleration
      transducers were attached to the suspension system to detect reference vibration
      and two loudspeakers were used to attenuate the noise near the headrests of two
      front seats. A leaky constraint multiple filtered-X LMS algorithm with an IIR
      based filter that has fast convergence speed and frequency selective
      controllability was proposed to increase the control efficiency in computing
      power and memory usage. During the test drive on the rough asphalt and turtle
      back road at a constant speed of 60 km/h, we were able to achieve a reduction of
      around 6 dB of A-weighted sound pressure level in the road booming noise range
      with the proposed algorithm, which could not be obtained with the conventional
      multiple filtered-X LMS algorithm.

PMID- 11831794
TI  - A stability analysis of a decentralized adaptive feedback active control system
      of sinusoidal sound in free space.
AB  - In some cases, the implementation of active control of sound in free space
      requires a large number of secondary sources and error sensors. In terms of
      control hardware, this may translate into considerable processing power
      requirement. A practical method to decrease processing power is to decentralize
      the control; that is, implement many single-input, single-output independent
      controllers operating simultaneously instead of a large multiple-input, multiple
      output system. The main drawback of decentralized control is the risk of global
      instability. The purpose of this paper is to derive conditions under which
      globally stable control system behavior can be obtained in the case of adaptive
      feedback decentralized control for a sinusoidal disturbance. The main objective
      is to give practical conditions derived from the small gain theorem and the
      Nyquist criterion for the stability of the control system. These conditions only
      take into account the geometrical arrangement of the secondary sources and error
      sensors. This analysis involves a new parameter beta called "performance index,"
      which is associated with both the convergence of the individual controllers and
      the global stability of the system. Simulation and experimental results are shown
      to illustrate the effectiveness of the developed analytical tools.

PMID- 11831795
TI  - Social survey of community response to a step change in aircraft noise exposure.
AB  - Community response to a step change in aircraft noise exposure associated with
      the opening of a new runway at Vancouver International Airport was documented in
      two rounds of telephone interviews. One round of interviews was conducted 15
      months prior to the start of operations on the new runway, while a second round
      of interviews was undertaken 21 months after the start of operations. The
      proportion of respondents who described themselves as "very" or "extremely"
      annoyed by aircraft noise in a residential area with increased aircraft noise
      exposure after the runway opening was markedly greater than that predictable from
      well-known dosage-response relationships. Analysis suggests that a good part of
      the "excess" annoyance is attributable to the net influence of nonacoustic
      factors.

PMID- 11831796
TI  - Inaccuracies in sound pressure level determination from room impulse response.
AB  - The integration over discrete squared room impulse response (RIR) leads to the
      sound pressure level (SPL). However, certain inaccuracies in SPL determination
      appear as a consequence of influences of finite integration upper limit (UL) and
      noise. Due to that, these influences are investigated using two types of RIRs:
      those generated by simulation and those measured in the room. The investigations
      show that for RIRs with sufficiently small noise floors (below -20 or -15 dB)
      acceptably small inaccuracies are obtained if the integration UL is placed at T/3
      (alternatively at T/4). A more general solution is to set UL at the knee
      representing the point where main decay intersects noise floor. For even smaller
      inaccuracies, it would be better to set UL at the point somewhat before the knee
      called optimal UL. The influences of finite integration UL and noise can also be
      reduced by implementation of finite UL compensation and noise subtraction.

PMID- 11831797
TI  - Judgments of noticeable differences in sound fields of concert halls caused by
      intensity variations in early reflections.
AB  - In concert halls early reflections combine with the direct sound and with
      reverberation to determine the subjective rating of a room's acoustics. Of
      interest is how variations in the amplitudes of these early reflections are
      related to the subjectively just-noticeable differences (jnd) in several
      important acoustical parameters for their wide range encountered in existing
      halls. Investigated were four subjective parameters, apparent source width (ASW),
      loudness, intimacy and clarity, which are related to the physical measurements,
      [1-IACC(E3)], G, ITDG, and C80, defined mathematically in Beranek [Concert and
      Opera Halls: How They Sound (Acoustical Society of America, New York, 1996)].
      Forty-eight types of sound fields were chosen in which to make variations in the
      amplitudes of early reflections and were reproduced electro-acoustically by
      multiple loudspeakers in an anechoic chamber. The results indicate that ASW and
      loudness are more sensitive to changes in the levels of early reflections, and
      were the primary parameters investigated. Although the number of subjects
      available with enough experience in listening classical music is limited and the
      measured jnd is an initial estimation, the jnd of [1-IACC(E3)] is measured as
      0.065+/-0.015 in variations of sound field structures and the jnd of G was
      measured as 0.25+/-0.15 dB, which is consistent with the results of previous
      studies.

PMID- 11831798
TI  - Super-resolution in time-reversal acoustics.
AB  - The phenomenon of super-resolution in time-reversal acoustics is analyzed
      theoretically and with numerical simulations. A signal that is recorded and then
      retransmitted by an array of transducers, propagates back though the medium, and
      refocuses approximately on the source that emitted it. In a homogeneous medium,
      the refocusing resolution of the time-reversed signal is limited by diffraction.
      When the medium has random inhomogeneities the resolution of the refocused signal
      can in some circumstances beat the diffraction limit. This is super-resolution. A
      theoretical treatment of this phenomenon is given, and numerical simulations
      which confirm the theory are presented.

PMID- 11831799
TI  - Spectral shapes of forward and reverse transfer functions between ear canal and
      cochlea estimated using DPOAE input/output functions.
AB  - It is widely assumed that the distortion characteristics of the cochlea are
      uniform across its length, or at least across some portion of its length. For
      each distortion product otoacoustic emission (DPOAE) input/output (I/O) function
      across frequency, there is a corresponding cochlear I/O function defined over the
      cochlear source region. An assumption of distortion invariance is adopted such
      that these cochlear I/O functions are identical across tonotopic place, which is
      testable in the sense that a single nonlinear function should adequately describe
      the set of DPOAE I/O functions across frequency. If so, the differences in
      measured DPOAE I/O functions across frequency are produced by differences in the
      forward stimulus transmission to the generation site, and reverse DP transmission
      back to the ear canal. The absolute transfer-function magnitude is not determined
      by this technique, but the spectral shapes across frequency and between ears are
      determined. The role of middle-ear functioning is implicit in the I/O functions
      because of its controlling influence on these transfer functions. Results have
      been obtained using the average DPOAE I/O functions measured in a population of
      healthy ears [Gorga et al., J. Acoust. Soc. Am. 107, 2128-2135 (2000)], and
      support the hypothesis of cochlear-distortion invariance. The measured forward
      and reverse transfer functions have a general bandpass characteristic, and a more
      narrow-band structure with similarities to the behavioral threshold curve.

PMID- 11831801
TI  - The use of distortion product otoacoustic emission suppression as an estimate of
      response growth.
AB  - Distortion product otoacoustic emission (DPOAE) levels in response to primary
      pairs (f2 = 2 or 4 kHz, L2 ranging from 20 to 60 dB SPL, L1 = 0.4L2 + 39 dB) were
      measured with and without suppressor tones (f3), which varied from 1 octave below
      to 1/2 octave above f2, in normal-hearing subjects. Suppressor level (L3) varied
      from -5 to 85 dB SPL. DPOAE levels were converted into decrements by subtracting
      the level in the presence of the suppressor from the level in the absence of a
      suppressor. DPOAE decrement vs L3 functions showed steeper slopes when f3 < f2
      and shallower slopes when f3 > f2. This pattern is similar to other measurements
      of response growth, such as direct measures of basilar-membrane motion, single
      unit rate-level functions, suppression of basilar-membrane motion, and discharge
      rate suppression from lower animals. As L2 increased, the L3 necessary to
      maintain 3 dB of suppression increased at a rate of about 1 dB/dB when f3 was
      approximately equal to f2, but increased more slowly when f3 < f2. Functions
      relating L3 to L2 in order to maintain a constant 3-dB reduction in DPOAE level
      were compared for f3 < f2 and for f3 approximately = f2 in order to derive an
      estimate related to "cochlear-amplifier gain." These results were consistent with
      the view that "cochlear gain" is greater at lower input levels, decreasing as
      level increases.

PMID- 11831800
TI  - Development of wide-band middle ear transmission in the Mongolian gerbil.
AB  - Stapes vibrations were measured in deeply anesthetized adult and neonatal (ages:
      14 to 20 days) Mongolian gerbils. In adult gerbils, the velocity magnitude of
      stapes responses to tones was approximately constant over the entire frequency
      range of measurements, 1 to 40 kHz. Response phases referred to pressure near the
      tympanic membrane varied approximately linearly as a function of increasing
      stimulus frequency, with a slope corresponding to a group delay of 30 micros. In
      neonatal gerbils, the sensitivity of stapes responses to tones was lower than in
      adults, especially at mid-frequencies (e.g., by about 15 dB at 10-20 kHz in
      gerbils aged 14 days). The input impedance of the adult gerbil cochlea,
      calculated from stapes vibrations and published measurements of pressure in scala
      vestibuli near the oval window [E. Olson, J. Acoust. Soc. Am. 103, 3445-3463
      (1998)], is principally dissipative at frequencies lower than 10 kHz.
      CONCLUSIONS: (a) middle-ear vibrations in adult gerbils do not limit the input to
      the cochlea up to at least 40 kHz, i.e., within 0.5 oct of the high-frequency
      cutoff of the behavioral audiogram; and (b) the results in both adult and
      neonatal gerbils are inconsistent with the hypothesis that mass reactance
      controls high-frequency ossicular vibrations and support the idea that the middle
      ear functions as a transmission line.

PMID- 11831802
TI  - Effects of reversible noise exposure on the suppression tuning of rabbit
      distortion-product otoacoustic emissions.
AB  - Distortion-product otoacoustic emissions (DPOAEs) at 2f1-f2 can be suppressed by
      the introduction of a third "suppressor" tone. Plotting the suppression of the
      DPOAE level against the changing frequency and level of the suppressor produces
      frequency-tuning functions referred to as suppression tuning curves (STCs). The
      dominant features of STCs, including their shape, are similar to the features of
      neural tuning curves (NTCs) recorded from single auditory nerve fibers. However,
      recent findings using reversible diuretics suggest that STCs do not provide the
      same measure of cochlear frequency selectivity as provided by NTCs. To determine
      if STCs are also insensitive to the adverse effects of excessive sounds, the
      present study exposed rabbits to a moderate-level noise that produced temporary
      threshold shift-like (TTS) effects on DPOAEs, and examined the influence of such
      exposures on STCs. DPOAEs were produced using primary tones with geometric-mean
      frequencies centered at 2.8 or 4 kHz, and with L1 and L2 values of 45/45, 50/35,
      50/50, and 55/45 dB SPL. STCs were obtained before and during recovery for a
      period of approximately 2 h immediately following, and at 1, 2, 3, and 7 d post
      exposure to a 2 kHz octave band noise, at levels and durations sufficient to
      cause significant but reversible reductions in DPOAE levels. STC data included
      tip center frequency, tip threshold, and Q10dB measures of tuning for suppression
      criteria of 3, 6, 9, and 12 dB. Recovery was variable between animals, but all
      rabbits recovered fully by 7 d post-exposure. STC center frequencies measured
      during the TTS typically tuned to a slightly higher frequency, while tip
      thresholds tended to decrease and Q10dB increase. Together, the results indicate
      that, despite similarities in the general properties of STCs and NTCs, these two
      types of tuning curves are affected differently following reversible cochlear
      insult.

PMID- 11831803
TI  - On the frequency dependence of the otoacoustic emission latency in hypoacoustic
      and normal ears.
AB  - Experimental measurements of the otoacoustic emission (OAE) latency of adult
      subjects have been obtained, as a function of frequency, by means of wavelet time
      frequency analysis based on the iterative application of filter banks. The
      results are in agreement with previous OAE latency measurements by Tognola et al.
      [Hear. Res. 106, 112-122 (1997)], as regards both the latency values and the
      frequency dependence, and seem to be incompatible with the steep 1/f law that is
      predicted by scale-invariant full cochlear models. The latency-frequency
      relationship has been best fitted to a linear function of the cochlear physical
      distance, using the Greenwood map, and to an exponential function of the cochlear
      distance, for comparison with derived band ABR latency measurements. Two sets of
      ears [94 audiometrically normal and 42 impaired with high-frequency (f > 3 kHz)
      hearing loss] have been separately analyzed. Significantly larger average
      latencies were found in the impaired ears in the mid-frequency range. Theoretical
      implications of these findings on the transmission of the traveling wave are
      discussed.

PMID- 11831805
TI  - Comment on "Eigenmode analysis of arbitrarily shaped two-dimensional cavities by
      the method of point matching".

PMID- 11831804
TI  - Relations among early postexposure noise-induced threshold shifts and permanent
      threshold shifts in the chinchilla.
AB  - Threshold shifts (TS) were measured at various times following a wide variety of
      noise exposures on over 900 chinchillas. An analysis of postexposure TS measures
      and noise-induced permanent threshold shift (PTS) showed that, across audiometric
      test frequency, there was a consistent relation between these variables of the
      form PTS (dB) = alpha(e(TS/beta) - 1), where, for a given test frequency, alpha
      (dB) and beta (dB) are constants. TSs were measured immediately following
      exposure (TS0), 24 h after exposure (TS24), and at several intermediate times in
      order to estimate the maximum TS (TSmax). Correlation between TS and PTS at the
      various test frequencies was highest for TS24. An analysis of the 90th-percentile
      PTS showed a linear growth of PTS with TS24 of approximately 0.7 dB PTS/dB TS24.
      These data provide some support, in the chinchilla model, for a variation of the
      three postulates originally presented by Kryter et al. [J. Acoust. Soc. Am. 39,
      451 (1966)]. Specifically: (i) TS24 is a consistent measure of the effects of a
      traumatic noise exposure. (ii) All exposures that produce a given TS24 will be
      equally hazardous. (iii) Noise-induced PTS in the most susceptible animals,
      following many years of exposure, is approximately equal to (0.7)TS24 measured
      after an 8-h exposure to the same noise.

PMID- 11831806
TI  - Binaural detection with narrowband and wideband reproducible noise maskers: I.
      Results for human.
AB  - This study investigated binaural detection of tonal targets (500 Hz) using sets
      of individual masker waveforms with two different bandwidths. Previous studies of
      binaural detection with wideband noise maskers show that responses to individual
      noise waveforms are correlated between diotic (N0S0) and dichotic (N0S(pi))
      conditions [Gilkey et al., J. Acoust. Soc. Am. 78, 1207-1219 (1985)]; however,
      results for narrowband maskers are not correlated across interaural
      configurations [Isabelle and Colburn, J. Acoust. Soc. Am. 89, 352-359 (1991)].
      This study was designed to allow direct comparison, in detail, of responses
      across bandwidths and interaural configurations. Subjects were tested on a
      binaural detection task using both narrowband (100-Hz bandwidth) and wideband
      (100 Hz to 3 kHz) noise maskers that had identical spectral components in the 100
      Hz frequency band surrounding the tone frequency. The results of this study were
      consistent with the previous studies: N0S0 and N0S(pi) responses were more
      strongly correlated for wideband maskers than for narrowband maskers. Differences
      in the results for these two bandwidths suggest that binaural detection is not
      determined solely by the masker spectrum within the critical band centered on the
      target frequency, but rather that remote frequencies must be included in the
      analysis and modeling of binaural detection with wideband maskers. Results across
      the set of individual noises obtained with the fixed-level testing were
      comparable to those obtained with a tracking procedure which was similar to the
      procedure used in a companion study of rabbit subjects [Zheng et al., J. Acoust.
      Soc. Am. 111, 346-356 (2002)].

PMID- 11831807
TI  - Binaural detection with narrowband and wideband reproducible noise maskers: II.
      Results for rabbit.
AB  - Binaural detection with narrowband and wideband noise maskers was examined by
      using a Pavlovian-conditioned eyeblink response in rabbits. The target was a tone
      at 500 Hz, and the maskers were ten individual noise samples having one of two
      bandwidths, 200 Hz (410 Hz to 610 Hz) or 2900 Hz (100 Hz to 3 kHz). The
      narrowband noise maskers were created by filtering the wideband noise maskers
      such that the two sets of maskers had identical spectra in the 200-Hz frequency
      region surrounding the tone. The responses across the set of noise maskers were
      compared across bandwidths and across interaural configurations (N0S0 and
      N0S(pi)). Responses across the set of noise waveforms were not strongly
      correlated across bandwidths; this result is inconsistent with models for
      binaural detection that depend only upon the narrow band of energy centered at
      the frequency of the target tone. Responses were correlated across interaural
      configurations for the wideband masker condition, but not for the narrowband
      masker. All of these results were consistent with the companion study of human
      listeners [Evilsizer et al., J. Acoust. Soc. Am. 111, 336-345 (2002)] and with
      the results of human studies of binaural detection that used only wideband
      [Gilkey et al., J. Acoust. Soc. Am. 78, 1207-1219 (1985)] or narrowband [Isabelle
      and Colburn, J. Acoust. Soc. Am. 89, 352-259 (1991)] individual noise maskers.

PMID- 11831808
TI  - Effects of frequency-shifted auditory feedback on voice F0 contours in syllables.
AB  - Previous studies have shown that, during continuous vocalization, voice
      fundamental frequency (voice F0) is modified by frequency-shifted auditory
      feedback. In this study, the effects of frequency-shifted auditory feedback on
      voice F0 contours were determined for the first two syllables of the nonsense
      word [tatatas]. Results show that voice F0 is auditorily controlled with a long
      latency and responses are not interrupted by the onset and offset of phonation
      itself. Furthermore, after-effects were found in voice F0 in trials after the
      termination of the frequency shift, which indicates that the response persists
      for several seconds. It is argued that the purpose of the auditory-vocal system
      is not to control voice F0 precisely within single syllables, but rather on a
      supra-segmental level in the context of prosody.

PMID- 11831809
TI  - Regulating glottal airflow in phonation: application of the maximum power
      transfer theorem to a low dimensional phonation model.
AB  - Two competing views of regulating glottal airflow for maximum vocal output are
      investigated theoretically. The maximum power transfer theorem is used as a
      guide. A wide epilarynx tube (laryngeal vestibule) matches well with low glottal
      resistance (believed to correspond to the "yawn-sigh" approach in voice therapy),
      whereas a narrow epilarynx tube matches well with a higher glottal resistance
      (believed to correspond to the "twang-belt" approach). A simulation model is used
      to calculate mean flows, peak flows, and oral radiated pressure for an impedance
      ratio between the vocal tract (the load) and the glottis (the source). Results
      show that when the impedance ratio approaches 1.0, maximum power is transferred
      and radiated from the mouth. A full update of the equations used for simulating
      driving pressures, glottal flow, and vocal tract input pressures is provided as a
      programming guide for those interested in model development.

PMID- 11831811
TI  - Speech dynamic range and its effect on cochlear implant performance.
AB  - This study examines optimal conversions of speech sounds to audible electric
      currents in cochlear-implant listeners. The speech dynamic range was measured for
      20 consonants and 12 vowels spoken by five female and five male talkers. Even
      when the maximal root-mean-square (rms) level was normalized for all phoneme
      tokens, both broadband and narrow-band acoustic analyses showed an approximately
      50-dB distribution of speech envelope levels. Phoneme recognition was also
      obtained in ten CLARION implant users as a function of the input dynamic range
      from 10 to 80 dB in 10-dB steps. Acoustic amplitudes within a specified input
      dynamic range were logarithmically mapped into the 10-20-dB range of electric
      stimulation typically found in cochlear-implant users. Consistent with acoustic
      data, the perceptual data showed that a 50-60-dB input dynamic range produced
      optimal speech recognition in these implant users. The present results indicate
      that speech dynamic range is much greater than the commonly assumed 30-dB range.
      A new amplitude mapping strategy, based on envelope distribution differences
      between consonants and vowels, is proposed to optimize acoustic-to-electric
      mapping of speech sounds. This new strategy will use a logarithmic map for low
      frequency channels and a more compressive map for high-frequency channels, and
      may improve overall speech recognition for cochlear-implant users.

PMID- 11831812
TI  - Effects of phoneme class and duration on the acceptability of temporal
      modifications in speech.
AB  - Human subjective acceptability of durational distortions in speech segments or
      portions is significantly affected by various segmental and sequential
      properties, e.g., the vowel color and temporal position in a word [Kato et al.,
      J. Acoust. Soc. Am. 101, 2311-2322 (1997); 104, 540-549 (1998)]. The current
      study focused on the effects of phoneme class and original duration of speech
      portions in isolated words. In experiment 1, the effect of four classes of
      phoneme, i.e., vowel, nasal, voiceless fricative, and silent closure, on the
      acceptable modification range was tested. Six listeners evaluated the temporal
      acceptability of each of 49 words where one of the steady-state portions was
      subjected to durational modification from -75 ms (for shortening) to +75 ms (for
      lengthening) in 7.5-ms steps. The results showed that the listeners' acceptable
      modification ranges were narrowest for vowels, and widest for voiceless
      fricatives and silent closures, with nasals in between. The mean acceptable
      ranges for the least vulnerable phoneme class, i.e., voiceless fricative and
      silent closure, reached 143% or more of that for the most vulnerable class, i.e.,
      vowel. The observed variation in the acceptable modification range due to the
      different phoneme class was highly correlated with the inherent loudness in each
      phoneme class. A larger inherent loudness yielded a narrower acceptable range.
      Experiment 2 tested the effect of the original, as produced, duration of steady
      state speech portions using 30 words where the factors of phoneme class and
      original duration were designed in a factorial way. The results showed that the
      original durations affected the listeners' absolute acceptable ranges; the ranges
      were narrower for shorter original durations. There was a significant interaction
      between the factors of phoneme class and original duration. The effect of the
      original duration was larger for vowels than for fricatives. This interaction
      could be accounted for by the difference in the temporal structure spanning
      beyond the modified portion itself.

PMID- 11831813
TI  - The relationship between the intelligibility of time-compressed speech and speech
      in noise in young and elderly listeners.
AB  - A conventional measure to determine the ability to understand speech in noisy
      backgrounds is the so-called speech reception threshold (SRT) for sentences. It
      yields the signal-to-noise ratio (in dB) for which half of the sentences are
      correctly perceived. The SRT defines to what degree speech must be audible to a
      listener in order to become just intelligible. There are indications that elderly
      listeners have greater difficulty in understanding speech in adverse listening
      conditions than young listeners. This may be partly due to the differences in
      hearing sensitivity (presbycusis), hence audibility, but other factors, such as
      temporal acuity, may also play a significant role. A potential measure for the
      temporal acuity may be the threshold to which speech can be accelerated, or
      compressed in time. A new test is introduced where the speech rate is varied
      adaptively. In analogy to the SRT, the time-compression threshold (or TCT) then
      is defined as the speech rate (expressed in syllables per second) for which half
      of the sentences are correctly perceived. In experiment I, the TCT test is
      introduced and normative data are provided. In experiment II, four groups of
      subjects (young and elderly normal-hearing and hearing-impaired subjects)
      participated, and the SRT's in stationary and fluctuating speech-shaped noise
      were determined, as well as the TCT. The results show that the SRT in fluctuating
      noise and the TCT are highly correlated. All tests indicate that, even after
      correction for the hearing loss, elderly normal-hearing subjects perform worse
      than young normal-hearing subjects. The results indicate that the use of the TCT
      test or the SRT test in fluctuating noise is preferred over the SRT test in
      stationary noise.

PMID- 11831814
TI  - Recognition of low-pass-filtered consonants in noise with normal and impaired
      high-frequency hearing.
AB  - People with high-frequency hearing loss often complain of difficulty
      understanding speech, particularly in noisy environments. The reduction in
      audible high-frequency speech information provides one explanation. In addition,
      high-frequency hearing loss may reduce the contribution from the "tails" of high
      frequency auditory nerve fibers, resulting in diminished availability of lower
      frequency speech cues. This study was designed to determine if high-frequency
      hearing loss results in speech-understanding deficits beyond those accounted for
      by reduced high-frequency speech information. Recognition of speech, both low
      pass filtered and unfiltered, was measured for subjects with normal hearing and
      those with hearing loss limited to high frequencies. Nonsense syllables were
      presented in three levels of noise that was spectrally shaped to match the long
      term spectrum of the speech. Scores for subjects with impaired high-frequency
      hearing were significantly poorer than scores for subjects with normal hearing.
      In the case of the low-pass-filtered speech, performance differences between
      groups could not be attributed to differences in speech audibility, as high
      frequency speech cues were absent for all subjects. These results are consistent
      with the hypothesis that high-frequency fibers encode useful low-frequency speech
      information.

PMID- 11831815
TI  - Reduction of noise transmission through an aperture using active feedforward
      noise control.

PMID- 11831816
TI  - Effects of prosodic factors on spectral dynamics. I. Analysis.
AB  - The effects of prosodic factors on the spectral rate of change of vowel
      transitions are investigated. Thirty two-syllable English words are placed in
      carrier phrases and read by a single speaker. Liquid-vowel, diphthong, and vowel
      liquid transitions are extracted from different prosodic contexts, corresponding
      to different levels of stress, pitch accent, word position, and speaking style,
      following a balanced experimental design. The spectral rate of change in these
      transitions is measured by fitting linear regression lines to the first three
      formants and computing the root-mean-square of the slopes. Analysis shows that
      the spectral rate of change increases with linguistic prominence, i.e., in
      stressed syllables, in accented words, in sentence-medial words, and in
      hyperarticulated speech. The results are consistent with a contextual view of
      vowel reduction, where the extent of reduction depends both on the spectral rate
      of change and on vowel duration. A numerical model of spectral rate of change is
      proposed, which can be integrated in a system for concatenative speech synthesis,
      as discussed in Paper II [J. Wouters and M. Macon, J. Acoust. Soc. Am. 111, 428
      438 (2002)].

PMID- 11831817
TI  - Effects of prosodic factors on spectral dynamics. II. Synthesis.
AB  - In Paper I [J. Wouters and M. Macon, J. Acoust. Soc. Am. 111, 417-427 (2002)],
      the effects of prosodic factors on the spectral rate of change of phoneme
      transitions were analyzed for a balanced speech corpus. The results showed that
      the spectral rate of change, defined as the root-mean-square of the first three
      formant slopes, increased with linguistic prominence, i.e., in stressed
      syllables, in accented words, in sentence-medial words, and in clearly
      articulated speech. In the present paper, an initial approach is described to
      integrate the results of Paper I in a concatenative synthesis framework. The
      target spectral rate of change of acoustic units is predicted based on the
      prosodic structure of utterances to be synthesized. Then, the spectral shape of
      the acoustic units is modified according to the predicted spectral rate of
      change. Experiments show that the proposed approach provides control over the
      degree of articulation of acoustic units, and improves the naturalness and
      intelligibility of concatenated speech in comparison to standard concatenation
      methods.

PMID- 11831818
TI  - Shear wave focusing for three-dimensional sonoelastography.
AB  - A new vibration scheme is shown to provide localized vibration fields for three
      dimensional sonoelastography imaging. The theoretical vibration distributions of
      double strip loads vibrating normally to the surface of a semi-infinite elastic
      space are calculated. A localization or focusing of shear waves inbetween the
      double-strip loads is predicted. Experimentally, two parallel rigid rectangular
      cross-section bars are mounted on an electromagnetic shaker. Driven by the signal
      source, the bars vibrate against the surface of a tissue-mimicking phantom. The
      double-bar source is also used to propagate shear wave into an ex vivo prostate
      phantom with a 6 mm "tumor" in it. A combination of high frequencies (400-600 Hz)
      is used to drive the double-bar applicator. In the phantom experiments, a shear
      wave focal zone with higher vibration amplitude and uniformity predicted by the
      theory was confirmed. The position of the focal zone is controllable when
      adjusting the separation of the bars as the theory shows. When this vibration
      scheme was used in a prostate phantom experiment, high-resolution tumor images
      with clear boundaries are obtained. The parallel bar is an ideal applicator to
      create more uniform vibration within a controllable localized volume. The field
      has uniformity especially in the direction along the bars.

PMID- 11831819
TI  - Low-frequency acoustic pressure, velocity, and intensity thresholds in a
      bottlenose dolphin (Tursiops truncatus) and white whale (Delphinapterus leucas).
AB  - The relative contributions of acoustic pressure and particle velocity to the low
      frequency, underwater hearing abilities of the bottlenose dolphin (Tursiops
      truncatus) and white whale (Delphinapterus leucas) were investigated by measuring
      (masked) hearing thresholds while manipulating the relationship between the
      pressure and velocity. This was accomplished by varying the distance within the
      near field of a single underwater sound projector (experiment I) and using two
      underwater sound projectors and an active sound control system (experiment II).
      The results of experiment I showed no significant change in pressure thresholds
      as the distance between the subject and the sound source was changed. In
      contrast, velocity thresholds tended to increase and intensity thresholds tended
      to decrease as the source distance decreased. These data suggest that acoustic
      pressure is a better indicator of threshold, compared to particle velocity or
      mean active intensity, in the subjects tested. Interpretation of the results of
      experiment II (the active sound control system) was difficult because of complex
      acoustic conditions and the unknown effects of the subject on the generated
      acoustic field; however, these data also tend to support the results of
      experiment I and suggest that odontocete thresholds should be reported in units
      of acoustic pressure, rather than intensity.

PMID- 11831820
TI  - Second harmonic sound field after insertion of a biological tissue sample.

PMID- 11831821
TI  - A comparison of material classification techniques for ultrasound inverse
      imaging.
AB  - The conjugate gradient method with edge preserving regularization (CGEP) is
      applied to the ultrasound inverse scattering problem for the early detection of
      breast tumors. To accelerate image reconstruction, several different pattern
      classification schemes are introduced into the CGEP algorithm. These
      classification techniques are compared for a full-sized, two-dimensional breast
      model. One of these techniques uses two parameters, the sound speed and
      attenuation, simultaneously to perform classification based on a Bayesian
      classifier and is called bivariate material classification (BMC). The other two
      techniques, presented in earlier work, are univariate material classification
      (UMC) and neural network (NN) classification. BMC is an extension of UMC, the
      latter using attenuation alone to perform classification, and NN classification
      uses a neural network. Both noiseless and noisy cases are considered. For the
      noiseless case, numerical simulations show that the CGEP-BMC method requires 40%
      fewer iterations than the CGEP method, and the CGEP-NN method requires 55% fewer.
      The CGEP-BMC and CGEP-NN methods yield more accurate reconstructions than the
      CGEP method. A quantitative comparison of the CGEP-BMC, CGEP-NN, and GN-UMC
      methods shows that the CGEP-BMC and CGEP-NN methods are more robust to noise than
      the GN-UMC method, while all three are similar in computational complexity.

PMID- 11831822
TI  - Variational method for estimating the effects of continuously varying lenses in
      HIFU, sonography, and sonography-based cross-correlation methods.
AB  - The effects of high intensity focused ultrasound (HIFU)-induced continuously
      varying thermal gradients on sound ray propagation were modeled theoretically.
      This modeling was based on Fermat's variational principle of least time for rays
      propagating in a continuously varying thermal gradient described by a radially
      symmetric heat equation. Such thermal lenses dynamically affect HIFU beam
      focusing, and simultaneously create ultrasonic geometric and intensity
      distortions and artifacts in monitoring devices. Techniques which are based upon
      ultrasonic cross-correlation methods, such as elastography and two-dimensional
      temperature estimation, also suffer distortion effects and generate artifacts.

PMID- 11831824
TI  - A k-space method for coupled first-order acoustic propagation equations.
AB  - A k-space method for large-scale simulation of ultrasonic pulse propagation is
      presented. The present method, which solves the coupled first-order differential
      equations for wave propagation in inhomogeneous media, is derived in a simple
      form analogous to previous finite-difference methods with staggered spatial and
      temporal grids. Like k-space methods based on second-order wave equations, the
      present method is exact for homogeneous media, unconditionally stable for "slow"
      [c(r) < or = c0] media, and highly accurate for general weakly scattering media.
      In addition, unlike previous k-space methods, the form of the method allows
      straightforward inclusion of relaxation absorption and perfectly matched layer
      (PML) nonreflecting boundary conditions. Numerical examples illustrate the
      capabilities of the present k-space method. For weakly inhomogeneous media,
      accurate results are obtained using coarser temporal and spatial steps than
      possible with comparable finite-difference and pseudospectral methods. The low
      dispersion of the k-space method allows accurate representation of frequency
      dependent attenuation and phase velocity associated with relaxation absorption. A
      technique for reduction of Gibbs phenomenon artifacts, in which compressibility
      and exponentially scaled density functions are smoothed by half-band filtering,
      is introduced. When employed together with this smoothing technique, the k-space
      method provides high accuracy for media including discontinuities, high-contrast
      inhomogeneities, and scattering structures smaller than the spatial grid
      resolution.

PMID- 11831825
TI  - The effect of fluid loading on radiation efficiency.
AB  - The metric "radiation efficiency," used to estimate a panel's radiated acoustic
      power from a measure of its normal velocity, is typically derived under the
      condition of very light fluid loading. This paper shows that efficiencies
      calculated in this manner can significantly overestimate the radiated power when
      the condition of light fluid loading is not met, as can be the case for steel
      plates in water. It is also shown that, when fluid loading is not light, a
      baffled semi-infinite plate is not a good model for an interior support.
      Numerical results are presented for radiation efficiencies calculated for steel
      plates in water, and are compared to those calculated under the assumption of
      vanishing fluid loading.

PMID- 11831826
TI  - Theory of non-collinear interactions of acoustic waves in an isotropic material
      with hysteretic quadratic nonlinearity.
AB  - A particular form of the energy potential (cubic in strains) is proposed, which
      leads to the bow-tie behavior of the nonlinear modulus in an isotropic material
      with hysteresis of quadratic nonlinearity. The nonlinear scattering of a weak
      probe wave in the field of a strong pump wave is analyzed. It is demonstrated
      that collinear interactions of the shear waves are allowed in materials with
      nonlinearity hysteresis. Both in collinear and non-collinear frequency-mixing
      processes the combination frequency is composed of the probe wave frequency and
      one of the even harmonics of the pump wave. In general, the developed theory
      predicts that in the presence of the hysteretic nonlinearity the number of
      possible resonant scattering processes increases. In particular, if frequency
      mixing processes are forbidden in the material with the elastic quadratic
      nonlinearity (for a fixed ratio of primary frequencies), they may be allowed in
      the materials with hysteretic quadratic nonlinearity. Moreover, in materials with
      hysteresis of the nonlinearity the resonant frequency mixing for a fixed ratio of
      primary frequencies may be allowed for multiple mutual orientations of the
      primary wave vectors.

PMID- 11831827
TI  - Nonlinearity of acoustic waves at solid-liquid interfaces.
AB  - The small-amplitude and finite-amplitude propagation characteristics of laser
      line source excited and laser detected Scholte waves are investigated. Acoustic
      waves with Mach numbers up to 0.054 are observed at the interface between water
      and glass. In our case of a hard solid-liquid interface, the Scholte wave
      propagates very much like a bulk wave, for which the simple-wave equation holds.
      The experimental results are well fitted with this model, extended with an
      attenuation term. An anomalously large (compared with low amplitude viscous
      effects) attenuation reveals possible leakage of energy from the Scholte wave to
      bulk waves, through a mechanism of nonlinear mixing between the different wave
      modes and viscosity induced turbulence.

PMID- 11831828
TI  - Coronary bypass grafting in South Thames: the correlation between clinical scores
      and waiting times.
AB  - To determine waiting times before surgery and their correlation with clinical
      need, we examined the files of 1049 patients on the waiting list for coronary
      bypass grafting in 1996. The total waiting time to bypass grafting was 279 (SD
      209) days (range 1-1579 days). Waiting time to specialist consultation was 36 (SD
      43) days, and time on the waiting list for coronary angiography was 85 (SD 89)
      days. The mean time on the surgical waiting list was 133 (SD 134) days. Patients
      with a Birmingham clinical score below 10 waited between 27 and 879 days, and
      patients with scores above 35 waited between 3 and 282 days. Total waiting time
      was weakly associated with the priority score (Pearson correlation = -0.51). We
      conclude that waiting times were long with wide variation at every stage between
      referral and coronary bypass grafting. There was little correlation between
      clinical scores and waiting times.

PMID- 11831829
TI  - Evil: origins and potential solutions.

PMID- 11831830
TI  - The current physiotherapy management of patients with bronchiectasis: a UK
      survey.
AB  - The purpose of this survey was to ascertain which physiotherapy techniques are
      currently used, how interventions are assessed and to determine the views of
      physiotherapists in the UK on the need for further research. Senior
      physiotherapists in 100 randomly selected hospitals providing respiratory care in
      the UK were sent a previously piloted questionnaire on their bronchiectasis
      practice. The response rate was 82%. A variety of physiotherapy treatment
      techniques and outcome measures are used, and there are no national guidelines on
      the physiotherapy management of patients with bronchiectasis. There is a clear
      need for research into the effectiveness of physiotherapy techniques in
      bronchiectasis including a cost-benefit analysis which would enable targeting of
      resources and the development of evidence-based practice guidelines.

PMID- 11831831
TI  - Current clinical practice of induction and maintenance immunotherapy for
      metastatic renal cell carcinoma.
AB  - Current systemic treatment of metastatic renal cell carcinoma revolves around the
      use of interleukin-2 and interferon-alpha, often in combination with 5
      fluorouracil. This article looks at the currently reported response rates for
      these modalities. It also looks at current practice as regards maintenance
      treatment, i.e. the continued therapeutic regimen following the initial response
      to the induction immunotherapy cycles.

PMID- 11831832
TI  - Chest pain clinics: hope or hype?

PMID- 11831833
TI  - The management of metastatic bone pain in a developing country: the role of
      radiotherapy as an adjunct to weak opioids.
AB  - Bone pain secondary to metastatic cancer is the commonest intractable pain and is
      a major concern in most oncology units the world over. Cancer pain management is
      multidisciplinary in approach, so there is no universal or singular modality of
      treatment. In a developing country like Nigeria, only external radiotherapy and
      adjuvant weak opioids are readily available, so it is of interest to review the
      response of these patients to this management option. This is a retrospective
      review of 92 patients aged 16-80 years with radiologically confirmed metastatic
      bone disease associated with pain who received external radiotherapy and weak
      analgesics. The results showed that 23 (25%) patients had a complete response and
      67 (73%) had a partial response within four weeks of treatment. Total response
      was over 90%, which suggests external radiotherapy has an effective palliative
      role. The study also demonstrated the pattern of bony involvement among the
      common cancers seen in our environment. The availability of strong opioids (e.g.
      morphine and pethidine) will obviously consolidate the gains achieved with
      external radiotherapy in the management of metastatic bone pain in our
      environment.

PMID- 11831835
TI  - Tegaserod: a novel, selective 5-HT4 receptor partial agonist for irritable bowel
      syndrome.
AB  - Irritable bowel syndrome (IBS) is a common functional bowel disorder of unknown
      aetiology. It is defined by the presence of gastrointestinal (GI) symptoms
      including abdominal pain/discomfort, bloating and bowel motor dysfunction. No
      available therapy is yet effective against all the symptoms of the disorder.
      Current treatments therefore target individual symptoms but may be accompanied by
      unpleasant side-effects. Tegaserod is a novel selective serotonin receptor type-4
      (5-HT4) partial agonist with structural similarity to 5-HT Tegaserod stimulates
      small bowel and colonic motility and helps to normalise GI function. Clinical
      trials using a patient's assessment of efficacy demonstrate that tegaserod
      significantly improves key symptoms of IBS: abdominal pain/discomfort, bloating
      and constipation. Tegaserod is well tolerated with an excellent safety profile
      and represents a significant treatment advance in this difficult-to-treat
      disorder.

PMID- 11831834
TI  - Amiodarone-induced thyrotoxicosis: not a benign condition.
AB  - Amiodarone is a heavily iodinated drug effective in the control of various
      tachyarrhythmias. Despite its undoubted benefit, treatment with amiodarone is not
      without risk, because a number of potentially serious side-effects may develop
      during therapy. Thyrotoxicosis is most commonly recognised but its potential
      consequences tend to be underestimated, and its treatment can be challenging and
      difficult. We report several cases of amiodarone-induced thyrotoxicosis which
      serve to highlight the potential severity of the condition.

PMID- 11831836
TI  - Use of a customised endotracheal tube for tracheostomy in the large neck.
AB  - Patients with huge necks who require a tracheostomy pose particular problems.
      This paper describes a technique to customise a standard endotracheal tube to
      make a long tracheostomy tube. This can be used as a short-term emergency airway.
      It is recommended because it is cheap, simple, safe and potentially life saving.

PMID- 11831837
TI  - The MRC/BHF Heart Protection Study: preliminary results.
AB  - The Heart Protection Study (HPS), with over 20,500 subjects, is the largest trial
      of statin therapy ever conducted. It provides important and definitive new
      information on women, the elderly, diabetics, and people with low baseline
      cholesterol pre-treatment and those with prior occlusive non-coronary vascular
      disease. It is a prospective double blind randomised controlled trial with a 2 x
      2 factorial design investigating prolonged use (>5 years) of simvastatin 40 mg
      and a cocktail of antioxidant vitamins (650 mg vitamin E, 250 mg vitamin C and 20
      mg beta-carotene). The HPS specifically included patients with high risk for
      coronary heart disease (CHD) but characteristics that excluded them from
      participation in previous statin trials. Simvastatin 40 mg treatment showed
      benefit across all patient groups regardless of age, gender or baseline
      cholesterol value and proved safe and well tolerated. Results show a 12%
      reduction in total mortality, a 17% reduction in vascular mortality, a 24%
      reduction in CHD events, a 27% reduction in all strokes and a 16% reduction in
      non-coronary revascularisations. Among high-risk patients in this western
      population (with a minimum total cholesterol [TC] > or = 3.5 mmol/l at entry)
      there appears to be no threshold cholesterol value below which statin therapy is
      not associated with benefit; even among those with pre-treatment cholesterol
      levels below current national recommended targets. Over the 5.5 year study period
      patients and their doctors were encouraged to add an active non-study statin to
      the study regimen if they wished to do so. Thus the trial eventually had only two
      thirds complying with the original intention-to-treat design. Nevertheless,
      results were highly significant for the study statin--simvastatin 40 mg once
      daily. Preliminary results of the HPS are negative for the antioxidant vitamin
      cocktail but provide reassurance that vitamins do no harm.

PMID- 11831838
TI  - Effect of verapamil in elderly patients with left ventricular diastolic
      dysfunction as a cause of congestive heart failure.
AB  - Fifteen elderly patients with normal left ventricular (LV) systolic function and
      New York Heart Association functional class II-III were studied. The effect of
      verapamil on LV diastolic function was assessed by congestive heart failure (CHF)
      score, treadmill exercise test, and Doppler echocardiography at baseline, and
      after each three-month treatment period (placebo or verapamil 120 mg once daily),
      separated by a one-week washout period before crossover. Blood pressure, heart
      rate, LV ejection fraction, LV mass, and cardiac output were unaltered by placebo
      or verapamil. Verapamil treatment significantly improved CHF score at 3 months
      (3.5 +/- 0.5, p<0.05) compared with baseline (5.6 +/- 0.5) or placebo (5.5 +/-
      0.5). The exercise time was similar at baseline (7.4 +/- 1.2 min) and after
      placebo (7.4 +/- 1.3 min) treatment but significantly (p<0.05) increased after
      verapamil (8.3 +/- 1.2 min) treatment. The ratio of mitral A wave
      duration/pulmonary venous atrial systolic reversal duration increased after
      verapamil (1.11 +/- 0.08) treatment compared with placebo (0.91 +/- 0.07, p<0.05)
      and baseline (0.89 +/- 0.08) which had similar durations. The isovolumic
      relaxation time was significantly (p<0.05) decreased from 84 +/- 12 ms at
      baseline and 86 +/- 13 ms with placebo to 73 +/- 9 ms with verapamil. The results
      of this study suggest that in elderly patients with Doppler evidence of diastolic
      dysfunction as the cause of CHF, three months treatment with verapamil can
      improve CHF, increase exercise tolerance and improve LV diastolic function.

PMID- 11831839
TI  - Waiting times for CABG in South Thames.

PMID- 11831840
TI  - Riedel's thyroiditis: clinical, pathological and imaging features.
AB  - Riedel's thyroiditis (RT) is an extremely rare form of chronic thyroiditis,
      characterised by a fibroinflammatory process which partially destroys the
      thyroid, often involving surrounding tissues. We describe an unusual case of RT
      in a 38-year-old woman, and discuss its typical clinical, pathological,
      ultrasound, radionuclide scanning and magnetic resonance findings. We conclude
      that the diagnosis of RT is highly suggestive in the presence of a hard gland (or
      nodule), fixed to adjacent structures; 'cold' on Tc99 scan; hypoechoic with
      absence of vascular flow, invading the adjacent neck structures on ultrasound;
      hypointense in T1- and T2-weighted MR images; and showing fibrous tissue
      fragments with inflammatory cells at cytological examination. Thyroidectomy has
      to be performed to confirm the diagnosis and to relieve pressure symptoms.

PMID- 11831841
TI  - Recurrent lentigo maligna melanoma: regression associated with local azelaic acid
      20%.
AB  - Azelaic acid has been used to treat different hyperpigmentary disorders because
      of its antimelanocyte activity. The efficacy of azelaic acid in the treatment of
      lentigo maligna and melanoma has already been described and this local treatment
      is considered by some as an alternative agent when other forms of therapy are not
      realisable. Here we report a case of a patient with local recurrence of a stage
      IV lentigo maligna melanoma of the cheek which cleared after treatment with
      azelaic acid cream 20%.

PMID- 11831842
TI  - Patient perspective on zanamivir in the treatment of influenza.
AB  - Placebo-controlled clinical studies have shown zanamivir to be an effective
      treatment of influenza A and influenza B illness. This survey, conducted in
      France, was done to evaluate patients' perception of zanamivir in clinical
      practice. Between January and mid-April 2000, 271 retail pharmacists gave
      questionnaires to patients with a prescription for zanamivir to be completed on a
      voluntary basis. A total of 514 patients returned completed questionnaires, of
      whom 97 (19%) were considered at high risk of developing influenza complications.
      Fifty-one (10%) patients, mainly those over 65 years, were vaccinated against
      influenza. Fever or feverishness was reported by 93% of patients, and cough,
      myalgia and headache by 72%. Most (58%) patients consulted their doctor within 24
      hours of the onset of symptoms, and 96% within 48 hours. Eighty-five per cent of
      patients overall and 82% of high-risk individuals (82/97) reported being
      satisfied with their zanamivir treatment. Treatment compliance was high with 75%
      of patients completing the whole course of treatment. Symptom relief was reported
      by 45% of patients within 24 hours and by 74% of patients within 48 hours; 66% of
      patients resumed normal activities within 72 hours. These results suggest that
      patient satisfaction is high and compliance with zanamivir is highly
      satisfactory. In addition, the use of zanamivir was reported to be associated
      with rapidsymptom relief and return to normal activity

PMID- 11831843
TI  - Granulocyte colony stimulating factor treatment for delayed recovery of
      ticlopidine-related neutropenia.
AB  - We describe the case of a patient who developed neutropenia associated with
      sepsis and endophthalmitis after ticlopidine therapy for coronary stenting. The
      neutropenia did not resolve until granulocyte colony stimulating factor (G-CSF)
      was given. This uncommon case brings to attention the need for the immediate use
      of G-CSF in patients with delayed recovery from drug-related neutropenia and
      severe infection.

PMID- 11831844
TI  - The carboxy terminal C-tail of BNip3 is crucial in induction of mitochondrial
      permeability transition in isolated mitochondria.
AB  - BNip3 is a member of Bcl-2 family proteins that displays proapoptotic activity.
      It contains Bcl-2 homology (BH) 3 and single carboxy terminal membrane-anchoring
      domain (TM), which targets to specific intracellular organelles, especially to
      mitochondria. Mitochondria play significant roles in apoptosis by releasing
      apoptogenic factors through large conductance channel known as permeability
      transition pore (PTP). Although BNip3 associates with mitochondria when
      overexpressed, apoptotic pathways including mitochondrial cascade and functional
      domains of BNip3 are still unknown. In this report, we demonstrate that
      recombinant BNip3 (rBNip3) induces mitochondrial permeability transition (MPT)
      and cytochrome c release from isolated mitochondria, which are inhibited by the
      PT inhibitor cyclosporin A (CsA). We further show that carboxy terminal tail of
      BNip3, but not BH3, is essential for the induction of PT and cytochrome c release
      on the base of mutational analysis. Moreover, addition of carboxy terminal c-tail
      to TM substitution mutant, which did not induce the PT and cytochrome c release,
      restored PT-inducing activity. Taken together, our results suggest that BNip3
      exerts proapoptotic activity through PT induction and that carboxy terminal c
      tail is crucial for it.

PMID- 11831845
TI  - Characterization of nuclear gangliosides in rat brain: concentration,
      composition, and developmental changes.
AB  - Nuclear gangliosides were characterized using two distinct fractions of large
      (N1) and small (N2) nuclear populations from rat brain. The ganglioside
      concentration of N1 nuclei from adult rat brain was 0.92 microg sialic acid/mg
      protein, which was about 3.8 times higher than that of N2 nuclei. N1 and N2
      nuclear gangliosides showed similar compositional profiles; they contained major
      gangliosides of GM1, GD1a, GD1b, and GT1b, with GM3 in lesser amounts. c-Series
      gangliosides such as GT3, GQ1c, and GP1c were also detected in both nuclear
      preparations. Nuclear localization of gangliosides was confirmed by
      immunofluorescence with anti-GM1 antibody, cholera toxin B subunit, and c-series
      ganglioside-specific monoclonal antibody A2B5. Developmental changes of nuclear
      gangliosides were examined using rats of different ages ranging from embryonic
      day 14 (E14) to postnatal 7 weeks. The concentration of N1 nuclear gangliosides
      changed only slightly during development and did not correlate with that of whole
      brain gangliosides. The developmental pattern of ganglioside composition of N1
      nuclei was also distinguished from that of microsomal membranes; the ganglioside
      changes in N1 nuclei included reduced expression of di- and polysialogangliosides
      at E16 and higher proportions of GM3 at early and late stages of the period.
      These findings suggest that gangliosides in nuclear membranes are developmentally
      regulated in a distinct manner in brain cells.

PMID- 11831846
TI  - Localization and characterization of the mitochondrial isoform of the nucleoside
      diphosphate kinase in the pancreatic beta cell: evidence for its complexation
      with mitochondrial succinyl-CoA synthetase.
AB  - Nucleoside diphosphate kinase (NDPK) catalyzes the transfer of terminal
      phosphates from nucleoside triphosphates to nucleoside diphosphates to yield
      nucleotide triphosphates. The present study was undertaken to localize and
      characterize the mitochondrial isoform of NDPK (mNDPK) in the pancreatic beta
      cell since it could contribute to the generation of mitochondrial nucleotide
      triphosphates and, thereby, to the mitochondrial high-energy phosphate metabolism
      of the pancreatic beta cell. Mitochondrial fractions from the insulin-secreting
      beta cells were isolated by differential centrifugation. mNDPK activity was
      assayed as the amount of [(3)H]GTPgammaS formed from ATPgammaS and [(3)H]GDP.
      Incubation of isolated mitochondrial extracts with either [gamma-(32)P]ATP or GTP
      resulted in the formation [(32)P]NDPK, which could be immunoprecipitated by an
      anti-NDPK serum. mNDPK exhibited saturation kinetics with respect to its
      nucleoside diphosphate acceptors and nucleoside triphosphate donors and
      sensitivity to known inhibitors of NDPK (e.g., uridine diphosphate and
      cromoglycate). By Western blot analyses, at least three isoforms of NDPK were
      identified in various subcellular fractions of the beta cell. The nm23-H1 (NDPK
      A) was predominantly soluble whereas nm23-H2 (NDPK-B) was associated with the
      soluble as well as membranous fractions. The mitochondrial isoform of NDPK, nm23
      H4, was uniformly distributed in the beta cell mitochondrial subfractions. A
      significant amount of NDPK (as determined by the catalytic activity and
      immunological methods) was recovered in the immunoprecipitates of mitochondrial
      fraction precipitated with an antiserum directed against succinyl-CoA synthetase
      (SCS), suggesting that NDPK might remain complexed with SCS. We provide the first
      evidence for the localization of a mitochondrial isoform of the NDPK in the islet
      beta cell and thus offer a potential mechanism for the generation of
      intramitochondrial GTP which, unlike ATP, is not transported into mitochondria
      via the classical nucleotide translocase. Further work will be required to
      determine the importance of the NDPK/SCS complex to normal beta cell function in
      the secretion of insulin.

PMID- 11831847
TI  - Saccharomyces cerevisiae ferrochelatase forms a homodimer.
AB  - Ferrochelatase, the last enzyme of the heme biosynthetic pathway, has for years
      been considered to be active as a monomer. The crystal structure of Bacillus
      subtilis ferrochelatase confirmed its monomeric structure. However, animal
      ferrochelatase was found to form a functional dimer. Data presented here indicate
      that ferrochelatase from the yeast Saccharomyces cerevisiae is also dimeric.
      Following two-hybrid studies that had shown an interaction of two ferrochelatase
      molecules, we employed several different, complementary approaches, such as
      chemical crosslinking, affinity chromatography, and complementation analysis, to
      prove that in the yeast cells ferrochelatase forms an active dimer. We have
      isolated a double mutant, hem15D246V/Y248F, which is probably dimerization
      defective. We propose a structural model of yeast ferrochelatase, based on the
      known structure of the human enzyme, which helps us to understand the differences
      in dimerization between the wild-type and mutant proteins.

PMID- 11831848
TI  - Remarkable phylum selectivity of a Schistocerca gregaria trypsin inhibitor: the
      possible role of enzyme-inhibitor flexibility.
AB  - A 35-mer polypeptide isolated from the hemolymph of desert locust Schistocerca
      gregaria (SG) proved to be a canonical inhibitor of bovine trypsin (K(i) = 0.2
      microM). Despite having a trypsin-specific arginine at the primary specificity
      P(1) site, it inhibits bovine chymotrypsin almost as well (K(i) = 2 microM).
      Furthermore, while the latter reactivity improves 10(4)-fold by the single
      replacement of P(1) Arg by Leu, changing P(1)' from Lys to Met only moderately
      improves trypsin affinity (K(i) = 30 nM). The apparent low compatibility to
      trypsin, however, is not observed vs two arthropodal trypsins: SG peptides with
      P(1) Arg inhibit crayfish and shrimp trypsins with K(i) values in the picomolar
      range. This unprecedented high discrimination between orthologous enzymes is
      postulated to derive from flexibility differences in the protein-protein
      interaction. The more than four orders of magnitude phylum selectivity makes
      these peptides prospective candidates for agricultural use.

PMID- 11831849
TI  - Active site mutations of cytochrome p450cam alter the binding, coupling, and
      oxidation of the foreign substrates (R)- and (s)-2-ethylhexanol.
AB  - Three factors are of primary importance with respect to designing efficient P450
      biocatalysts. (1) The substrate must be oxidized at a significant rate. (2) The
      regioselectivity must heavily favor the desired product. (3) The enzyme must use
      the majority of the reducing equivalents from NADH or NADPH to produce product.
      The reaction we chose to study was oxidation of 2-ethylhexanol to 2-ethylhexanoic
      acid by P450cam. We examined four active site mutations: F87W, Y96W, T185F, and
      L244A. The mutations were chosen to improve 2-ethyhexanoic acid production by
      decreasing active site volume, increasing active site hydrophobicity, and
      improving stereoselectivity. The F87W and Y96W mutations improved
      regioselectivity, giving almost exclusively the desired product. The T185F
      mutation improved coupling of NADH to product formation. The L244A mutation
      altered the stereoselectivity of 2-ethylhexanoic acid production. These results
      indicate that active site mutations of P450cam can alter catalysis of 2
      ethylhexanol.

PMID- 11831850
TI  - Fe(2+) induces a transient Ca(2+) release from rat liver mitochondria.
AB  - Isolated mitochondria loaded with Ca(2+) and then exposed to Fe(2+) show a
      transient release of Ca(2+). The magnitude of this response depends on the Ca(2+)
      loading and the kinetics of the response depends on the concentration of added
      Fe(2+). We investigated the Fe(2+)-induced Ca(2+) release mechanism by measuring
      mitochondrial Ca(2+) uptake in the presence of Fe(2+). The presence of Fe(2+)
      inhibits Ca(2+) uptake two times. Since mitochondria can cycle Ca(2+) across
      their inner membrane, the suppression of Ca(2+) uptake, but not release, results
      in an elevation of the extramitochondrial Ca(2+), thereby varying the steady
      state. The transient release of Ca(2+) initially observed from mitochondria
      appears to occur via the electroneutral 2H(+)/Ca(2+)-exchange mechanism, since it
      can be markedly decreased by cyclosporin A and does not involve lipid
      peroxidation. When Fe(2+) accumulation is completed, reuptake of released Ca(2+)
      into mitochondria resumes. Finally, we propose that Fe(2+) either inhibits Ca(2+)
      entry at the uniporter or is transported by it into the matrix.

PMID- 11831851
TI  - Complete amino acid sequence and characterization of the reaction mechanism of a
      glucosamine-induced novel alcohol dehydrogenase from Agrobacterium radiobacter
      (tumefaciens).
AB  - A glucosamine-induced novel alcohol dehydrogenase has been isolated from
      Agrobacterium radiobacter (tumefaciens) and its fundamental properties have been
      characterized. The enzyme catalyzes NAD-dependent dehydrogenation of aliphatic
      alcohols and amino alcohols. In this work, the complete amino acid sequence of
      the alcohol dehydrogenase was determined by PCR method using genomic DNA of A.
      radiobacter as template. The enzyme comprises 336 amino acids and has a molecular
      mass of 36 kDa. The primary structure of the enzyme demonstrates a high homology
      to structures of alcohol dehydrogenases from Shinorhizobium meliloti (83%
      identity, 90% positive) and Pseudomonas aeruginosa (65% identity, 76% positive).
      The two Zn(2+) ion binding sites, both the active site and another site that
      contributed to stabilization of the enzyme, are conserved in those enzymes.
      Sequences analysis of the NAD-dependent dehydrogenase family using a hypothetical
      phylogenetic tree indicates that these three enzymes form a new group distinct
      from other members of the Zn-containing long-chain alcohol dehydrogenase family.
      The physicochemical properties of alcohol dehydrogenase from A. radiobacter were
      characterized as follows. (1) Stereospecificity of the hydride transfer from
      ethanol to NADH was categorized as pro-R type by NMR spectra of NADH formed in
      the enzymatic reaction using ethanol-D(6) was used as substrate. (2) Optimal pH
      for all alcohols with no amino group examined was pH 8.5 (of the C(2)-C(6)
      alcohols, n-amyl alcohol demonstrated the highest activity). Conversely,
      glucosaminitol was optimally dehydrogenated at pH 10.0. (3) The rate-determining
      step of the dehydrogenase for ethanol is deprotonation of the enzyme-NAD-Zn
      OHCH(2)CH(3) complex to enzyme-NAD-Zn-O(-)CH(2)CH(3) complex and that for
      glucosaminitol is H(2)O addition to enzyme-Zn-NADH complex.

PMID- 11831852
TI  - Peroxynitrite oxidation of tubulin sulfhydryls inhibits microtubule
      polymerization.
AB  - Considerable evidence both in vitro and in vivo implicates protein damage by
      peroxynitrite as a probable mechanism of cell death. Herein, we report that
      treatment of bovine brain microtubule protein, composed of tubulin and
      microtubule-associated proteins, with peroxynitrite led to a dose-dependent
      inhibition of microtubule polymerization. The extent of cysteine oxidation
      induced by peroxynitrite correlated well with inhibition of microtubule
      polymerization. Disulfide bonds between the subunits of the tubulin heterodimer
      were detected by Western blot as a result of peroxynitrite-induced cysteine
      oxidation. Addition of disulfide reducing agents including dithiothreitol and
      beta-mercaptoethanol restored a significant portion of the polymerization
      activity that was lost following peroxynitrite addition. Thus, peroxynitrite
      induced disulfide bonds are at least partially responsible for the observed
      inhibition of polymerization. Sodium bicarbonate protected microtubule protein
      from the peroxynitrite-induced inhibition of polymerization. Tyrosine nitration
      of microtubule protein by 1 mM peroxynitrite increased approximately twofold when
      sodium bicarbonate was present whereas the extent of cysteine oxidation decreased
      from 7.5 to 6.3 mol cysteine/mol tubulin. These results indicate that cysteine
      oxidation of tubulin by peroxynitrite, rather than tyrosine nitration, is the
      primary mechanism of inhibition of microtubule polymerization.

PMID- 11831853
TI  - Interfacial activation of porcine pancreatic phospholipase A(2) studied with 7
      nitrobenz-2-oxa-1,3-diazol-4-yl-labeled lipids.
AB  - The interfacial activation of porcine pancreatic phospholipase A(2) (PLA(2))
      during the hydrolysis of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine liposomes at
      different temperatures has been monitored by fluorescence changes of the 7
      nitrobenz-2-oxa-1,3-diazol-4-yl (NBD) lipid derivatives 1-palmitoyl-2-[6-[(7
      nitro-2-1,3-benzoxadiazol-4-yl)amino]dodecanoyl]-sn-glycero-3-phosphocholine
      (C(12)-NBD-PC) and 12-[(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)]dodecanoic acid
      (C(12)-NBD-FA) inserted in the substrate vesicles. These long-chain monitors, in
      contrast to the previously used C(6)-NBD-PC, detect latency times of PLA(2)
      action, similar to those measured by the classic titrimetric, pH-stat method.
      Interestingly, hydrolysis of the host vesicles results in a decrease in
      fluorescence not only of C(12)-NBD-PC, a substrate analog, but also of product
      derivative C(12)-NBD-FA. Ultrafiltration experiments show that C(12)-NBD-FA does
      not migrate to the aqueous phase upon hydrolysis of the host liposomes. Besides,
      in a simulated hydrolysis experiment in which increasing proportions of palmitic
      acid and 1-palmitoyl-sn-glycero-3-phosphocholine were cosonicated with 1,2
      dipalmitoyl-sn-glycero-3-phosphocholine, C(12)-NBD-PC fluorescence was
      insensitive to products, whereas C(12)-NBD-FA did show a decreased emission
      intensity as in the actual hydrolysis experiments. The phenomenon is triggered
      above a critical concentration of products (10 mol%) suggesting that
      cosegregation of NBD-FA (either added as such or generated by hydrolysis of C(12)
      NBD-PC) and products may be related to the decrease in fluorescence. Phase
      separation should create microdomains of increased C(12)-NBD-FA surface density
      and cause concentration quenching. In addition, and taking into account that the
      NBD group may be located near the interfacial region, it is possible that in
      segregating with products, the fluorescent moiety of C(12)-NBD-FA becomes exposed
      to microenvironments of higher surface polarity, which further decreases its
      quantum yield.

PMID- 11831854
TI  - Biosynthesis of d-arabinose in Mycobacterium smegmatis: specific labeling from d
      glucose.
AB  - d-Arabinose is a major sugar in the cell wall polysaccharides of Mycobacterium
      tuberculosis and other mycobacterial species. The reactions involved in the
      biosynthesis and activation of d-arabinose represent excellent potential sites
      for drug intervention since d-arabinose is not found in mammalian cells, and the
      cell wall arabinomannan and/or arabinogalactan appear to be essential for cell
      survival. Since the pathway involved in conversion of d-glucose to d-arabinose is
      unknown, we incubated cells of Mycobacterium smegmatis individually with [1
      (14)C]glucose, [3,4-(14)C]glucose, and [6-(14)C]glucose and compared the specific
      activities of the cell wall-bound arabinose. Although the specific activity of
      the arabinose was about 25% lower with [6-(14)C]glucose than with other labels,
      there did not appear to be selective loss of either carbon 1 or carbon 6,
      suggesting that arabinose was not formed by loss of carbon 1 of glucose via the
      oxidative step of the pentose phosphate pathway, or by loss of carbon 6 in the
      uronic acid pathway. Similar labeling patterns were observed with ribose isolated
      from the nucleic acid fraction. Since these results suggested an unusual pathway
      of pentose formation, labeling studies were also done with [1-(13)C]glucose, [2
      (13)C]glucose, and [6-(13)C]glucose and the cell wall arabinose was examined by
      NMR analysis. This method allows one to determine the relative (13)C content in
      each carbon of the arabinose. The labeling patterns suggested that the most
      likely pathway was condensation of carbons 1 and 2 of fructose 6-phosphate
      produced by the transaldolase reaction with carbons 4, 5, and 6 (i.e.,
      glyceraldehyde 3-phosphate) formed by fructose-1,6 bisphosphate aldolase. Cell
      free enzyme extracts of M. smegmatis were incubated with ribose 5-phosphate,
      xylulose 5-phosphate, and d-arabinose 5-phosphate under a variety of experimental
      conditions. Although the ribose 5-phosphate and xylulose 5-phosphate were
      converted to other pentoses and hexoses, no arabinose 5-phosphate (or free
      arabinose) was detected in any of these reactions. In addition, these enzyme
      extracts did not convert arabinose 5-phosphate to any other pentose or hexose. In
      addition, incubation of [(14)C]glucose 6-phosphate and various nucleoside
      triphosphates (ATP, CTP, GTP, TTP, and UTP) with cytosolic or membrane fractions
      from the mycobacterial cells did not result in formation of a nucleotide form of
      arabinose, although other radioactive sugars including rhamnose and galactose
      were found in the nucleotide fraction. Furthermore, no radioactive arabinose was
      found in the nucleotide fraction isolated from M. smegmatis cells grown in
      [(3)H]glucose, nor was arabinose detected in a large-scale extraction of the
      sugar nucleotide fraction from 300 g of cells. The logical conclusion from these
      studies is that d-arabinose is probably produced from d-ribose by epimerization
      of carbon 2 of the ribose moiety of polyprenylphosphate-ribose to form
      polyprenylphosphate-arabinose, which is then used as the precursor for formation
      of arabinosyl polymers.

PMID- 11831856
TI  - Determination of the chlorine kinetic isotope effect on the 4-chlorobenzoyl-CoA
      dehalogenase-catalyzed nucleophilic aromatic substitution.
AB  - The chlorine kinetic isotope effect (KIE) on the dehalogenation of 4
      chlorobenzoyl-CoA catalyzed by 4-chlorobenzoyl-CoA dehalogenase has been measured
      at room temperature and optimal pH. The measured value of (37)k = 1.0090 +/-
      0.0006 is larger than the KIEs recently measured for haloalkane and fluoroacetate
      dehalogenase. This indicates that the transition state for dissociation of
      chloride ion from the Meisenheimer intermediate is sensitive to the chlorine
      isotopic substitution. Simple modeling suggests that this sensitivity originates
      in the high isotopic sensitivity of the C-Cl bond bending modes.

PMID- 11831855
TI  - Mapping the active site of endothelin-converting enzyme-1 through subsite
      specificity and mutagenesis studies: a comparison with neprilysin.
AB  - Endothelin-converting enzyme-1 (ECE-1) is a membrane-bound zinc metallopeptidase
      that is homologous to neprilysin in amino acid sequence. A major in vivo function
      of ECE-1 is the generation of endothelin-1, a potent vasoconstrictor, from big
      endothelin-1. ECE-1 is also potentially involved in the processing or degradation
      of other peptide hormones. In this study we have used substrates based on the
      sequence of the COOH-terminal half of big endothelin-1 to examine the subsite
      specificity of recombinant ECE-1. The big endothelin-1 [16-38] peptides were
      systematically varied at either position 21 (P(1)) or position 22 (P'(1)) and
      used in steady-state kinetic analyses of ECE-1. The results indicate that the
      S(1) pocket of ECE-1 is relatively nonselective, but that the S'(1) subsite of
      ECE-1 has a preference for large hydrophobic side chains. The peptidyl
      carboxydipeptidase activity of ECE-1 was also characterized, revealing that
      substrates with COOH-terminal carboxylates are highly preferred over the cognate
      amides and esters. A site-directed mutagenesis study was carried out to identify
      the active-site amino acid residues specifically involved in binding to the COOH
      terminal carboxylate of substrates. The data indicate that Arg(133) of ECE-1,
      which corresponds to Arg(102) of neprilysin that has been identified as an active
      site residue of neprilysin involved in binding to the free carboxylate of some
      substrate peptides, may not play the same role. However, the low activity
      observed for an ECE-1 Arg(726) mutant is consistent with a role for this arginine
      residue in the binding of substrates, a role which has been ascribed to arginine
      residues in both thermolysin (Arg(203)) and neprilysin (Arg(717)).

PMID- 11831857
TI  - Regulation of postaggregation events induced by protease-activated receptor 1
      ligation in human platelets: evidence of differential signaling pathways.
AB  - In a physiological milieu platelets continue to be exposed to agonists long after
      clot formation. We studied the regulation of postaggregation events consequent on
      protease-activated receptor (PAR) 1 ligation with either thrombin or the thrombin
      receptor-activating peptide (TRAP). Stimulation with TRAP (20 microM) but not
      with thrombin (1 U/ml) for 15 min evoked platelet disaggregation by about 30% and
      downregulation of high-affinity fibrinogen binding sites on integrin
      alpha(IIb)beta(3) to nearly prestimulation levels. Concurrently, only TRAP
      disorganized the actin-based cytoskeleton, with decrease in the cytoskeletal
      content of focal contact-associated proteins like integrin alpha(IIb)beta(3),
      Src, and focal adhesion kinase (FAK). While protein tyrosine kinases were
      activated during the initial period of platelet aggregation with either agonist,
      stimulation of protein tyrosine phosphatases determined the successive phase of
      reduced phosphotyrosine content. SHP-1, an abundant protein tyrosine phosphatase
      in the platelets, was tyrosine phosphorylated on challenge of PAR-1 and
      coprecipitated with two unidentified tyrosine phosphorylated proteins of 140 and
      60 kDa; in addition, SHP-1 tyrosine phosphorylation (which is associated with
      enhanced phosphatase activity) was sustained until 15 min. Activity of calpain
      was upregulated following incubation with thrombin and not with TRAP.
      Collectively, these data suggest that signaling pathways elicited by PAR-1
      agonists thrombin and TRAP are markedly different, which could have important
      implications on late platelet responses.

PMID- 11831858
TI  - The murine endogenous retrovirus MIA14 encodes an active aspartic proteinase that
      is functionally similar to proteinases from D-type retroviruses.
AB  - Murine intracisternal A-type particles (IAPs) are endogenous retroviruses showing
      sequence homologies to B/D- and avian C-type retroviruses and a gene expression
      strategy similar to that of D-type retroviruses. These viruses form immature
      particles in the endoplasmic reticulum and do not release extracellular virions,
      but are competent for retrotransposition within the virus-producing cell. It had
      been assumed that lack of polyprotein processing and maturation is due to a
      defect in the viral proteinase (PR), but recent experiments have shown that
      polyprotein processing occurs when assembly of the mouse IAP MIA14 is
      artificially directed to the plasma membrane. We have expressed and purified
      recombinant MIA14 PR and show that it undergoes N- and C-terminal autoprocessing
      at defined sites. Using peptide cleavage and inhibition assays and in vitro
      cleavage of recombinant HIV-1 and MIA14 Gag polyproteins, we show that MIA14 PR
      is a catalytically competent enzyme comparable in its efficiency to PRs from type
      D exogenous retroviruses. MIA14 PR is related to the PR of Mason-Pfizer monkey
      virus both functionally and with respect to its expression strategy, and is
      distinct from HIV-1 PR with respect to substrate specificity and catalytic
      efficiency. These findings reveal a functional and possibly evolutionary
      relationship between MIA14 and D-type retroviruses and imply that a functional PR
      may be relevant for intracellular retrotransposition even in the case of an
      endogenous retrovirus that does not produce extracellular virus.

PMID- 11831859
TI  - Continuous B-epitope maps of cytochrome P450cam (CYP101) obtained by peptide
      scanning: correlation to spatial structure.
AB  - Protein continuous B-epitopes can be revealed using short synthetic peptides that
      overlap a known protein sequence. Since the whole protein surface is considered
      to possess antigenic properties, a question that arises is whether a set of
      linear B-epitopes determined by peptide scanning correlates with a protein
      spatial structure. We have chosen cytochrome P450cam (CYP101) of Pseudomonas
      putida, with known 3D structure, as a template. Sera of two rabbits and antibody
      egg yolk preparations from three chickens were produced against the P450cam
      molecule. These polyclonals were analyzed separately in ELISA with 409
      overlapping P450cam hexapeptides. The whole set of continuous antigenic sites of
      P450cam covered about 45% of the P450cam sequence. However, immunodominant sites
      (those revealed with more than 50% antibody preparations), the so-called
      "antigenic core," represent only 9% of the protein sequence. While the amount of
      water-accessible residues in the total antigenic map (42%) was close to that in
      the whole native P450cam molecule (39%), the amount of water-accessible residues
      in the antigenic core was significantly higher (64%). These results led to the
      conclusion that antigenic core epitopes can be associated to the molecular
      surface, whereas epitopes with low detection frequency may partly correspond to
      unfolded regions of the protein molecule.

PMID- 11831860
TI  - Effects of isoflurane on voltage-dependent calcium fluxes in rabbit T-tubule
      membranes: comparison with alcohols.
AB  - The effects of racemic (+/-) and (+)- and (-)-stereoisomers of isoflurane on
      depolarization-induced (45)Ca(2+) fluxes mediated by voltage-dependent Ca(2+)
      channels were investigated in transverse tubule membrane vesicles from rabbit
      skeletal muscle. In the concentration range 0.5 to 2 mM, (+/-)-isoflurane
      inhibited (45)Ca(2+) fluxes and functionally modulated the effects of the Ca(2+)
      channel antagonist nifedipine (1-10 microM). Isoflurane-induced inhibition of
      (45)Ca(2+) fluxes was not significantly affected by pretreatment with either
      pertussis toxin (5 microg/ml) or phorbol 12-myristate 13-acetate (50 nM). Further
      experiments indicated that there were no significant differences between (+)- and
      (-)-stereoisomers of isoflurane with respect to the extent of inhibition of
      (45)Ca(2+) fluxes. Radioligand binding studies indicated that racemic and (+)-
      and (-)-isoflurane were equally effective in displacing the specific binding of
      [(3)H]PN 200-110 to transverse tubule membranes. There were no apparent
      differences between the effects of (+)- and (-)-isoflurane on the characteristics
      of [(3)H]PN 200-110 binding. Although the concentrations of isoflurane for the
      inhibitions of (45)Ca(2+) fluxes and radioligand bindings were similar, the
      concentrations of n-alcohols required for the inhibition of (45)Ca(2+) fluxes
      were lower than those for the displacement of radioligand. Comparison of the data
      for the displacement of [(3)H]PN 200-110 binding and the inhibition of (45)Ca(2+)
      fluxes by isoflurane and by n-alcohols suggested that both isoflurane and n
      alcohols may have more than a single binding site. In conclusion, results
      indicate that isoflurane, independent of intracellular Ca(2+) levels,
      nonstereospecifically inhibits the function of voltage-dependent Ca(2+) channels
      and this effect is mediated through multiple binding sites.

PMID- 11831861
TI  - New members of the platelet-derived growth factor family of mitogens.

PMID- 11831862
TI  - Acute intermittent porphyria: heterogeneity of mutations in the
      hydroxymethylbilane synthase gene in Italy.
AB  - Acute intermittent porphyria (AIP) is an autosomal disorder caused by molecular
      abnormalities in the gene coding for hydroxymethylbilane synthase (HMBS), the
      third enzyme in the heme biosynthetic pathway. So far, more than 170 different
      mutations responsible for AIP have been identified worldwide in the HMBS gene. In
      this study we have performed molecular characterization in 14 patients with
      suspected diagnosis of AIP and in 29 family members of Italian ancestry.
      Molecular analysis of the HMBS gene allowed us to identify 13 different mutations
      among 14 patients with reduced HMBS activity: 5 splicing defects (IVS9+22 G>A,
      612 G>T, IVS11-2 delA, IVS12+2 T>C, and IVS13-1 G>A), 1 small insertion (182
      insGA), 1 small deletion (730-731 delCT), and 6 missense/nonsense mutations (76
      C>T, 295 G>A, 331 G>A, 580 C>T, 673 C>T, and 874 C>T), resulting in single-amino
      acid substitutions or protein truncations. Six of these molecular abnormalities
      had already been described and 7 are new findings. In a previous work on an
      Italian population we detected 7 different mutations among 8 AIP patients. This
      study has raised to 18 the number of different mutations so far found among the
      Italian AIP population, 11 of which are new findings. We can conclude that the
      mutation screening in the Italian population contributes to improvement of the
      diagnostic approach of AIP and to establishing possible clustering of mutations
      in the Mediterranean area.

PMID- 11831863
TI  - Pathophysiology of a sickle cell trait mouse model: human alpha(beta)(S)
      transgenes with one mouse beta-globin allele.
AB  - As a potential model for sickle cell trait (AS), we examined mice containing one
      normal mouse beta-globin allele in combination with a human hemoglobin S
      (h(alpha)beta(S)) transgene (m(beta)/hS). The mice segregated into two
      subpopulations containing low and high proportions of hemoglobin S (m(beta)/hS1
      and m(beta)/hS2, respectively) that was associated with one or two human
      h(alpha)beta(S) transgenes. We noted striking kidney pathology (cortical cysts,
      hyperplastic tubules, and glomerulonephritis), increasing with age and with
      greater severity in m(beta)/hS1. mBeta/hS2 animals were largely tolerant to 5%
      O(2) for 1 h, whereas 80% of m(beta)/hS1 mice died, exhibiting acute
      sequestration of erythrocytes in spleen, liver, and heart. These pathologies
      appear to result from a decreased oxygen affinity of the hybrid (human
      alpha/mouse beta) hemoglobins with a mild beta-thalassemia phenotype. Thus, these
      mouse models of sickle trait seem to manifest their renal pathology and
      sensitivity to hypoxia by mechanisms related to low tissue oxygen delivery and
      are different from the human syndrome. Analyses of parameters such as P(50), red
      cell indices, and genetic background are necessary in establishing potential
      relevance of any mouse model of the sickle cell syndromes.

PMID- 11831864
TI  - Modulation of ICAM-1 expression in ECV304 cells by macrophage-released cytokines.
AB  - Transendothelial leukocyte trafficking during inflammation requires the
      expression of adhesion molecules such as human intercellular adhesion molecule-1
      (ICAM-1). ICAM-1 is constitutively expressed on the surface of endothelial cells
      and its levels increase in response to a variety of inflammatory mediators,
      including cytokines. Monocyte/macrophage cells play a crucial role in this
      context because, upon stimulation, they release proinflammatory cytokines which
      are responsible for the upregulation of adhesion molecules in endothelial cells.
      In the present study we investigated whether the modulation of macrophage
      activation and cytokine release is able to modulate ICAM-1 expression in
      endothelial cells. Dexamethasone was selectively delivered to macrophages by
      means of a red blood cell-mediated delivery system. Subsequent stimulation of
      macrophages by lipopolysaccharide (LPS) was found to inhibit NF-kB activation and
      tumor necrosis factor-alpha (TNF-alpha) release [R. Crinelli, A. Antonelli, M.
      Bianchi, L. Gentilini, S. Scaramucci, and M. Magnani (2000) Blood Cells Mol. Dis.
      26, 211-222]. Incubation with conditioned medium derived from LPS-stimulated
      macrophages receiving dexamethasone resulted in a 45% inhibition of ICAM-1 mRNA
      expression in ECV304 cells. In the same experimental system this reduced ICAM-1
      expression was paralleled by a reduced NF-kB DNA binding activity and a twofold
      higher level of IkB(alpha) in the cytosol of endothelial cells. Activation of
      ICAM-1 expression in ECV304 cells by macrophage-conditioned medium is not due to
      IFN-gamma stimulation since STAT-1 DNA binding remained unchanged. Furthermore,
      treatment of the macrophage-conditioned medium with a TNF-alpha-inactivating
      antibody resulted in the complete abrogation of induced ICAM-1 expression. These
      results suggest that TNF-alpha is the main cytokine released by LPS-stimulated
      macrophages able to promote ICAM-1 gene expression in endothelial cells.
      Modulation of the NF-kB activation pathway in macrophages by targeted delivery of
      dexamethasone could potentially be used as a therapeutic strategy with which to
      inhibit the expression of ICAM-1 in endothelial cells.

PMID- 11831865
TI  - Developmental expression of vitamin K-dependent gamma-carboxylase activity in
      zebrafish embryos: effect of warfarin.
AB  - Vitamin K-dependent gamma-carboxylation is an essential posttranslational
      modification required for the functional activity of coagulation proteins such as
      factors VII, IX, X, and prothrombin. Warfarin, an inhibitor of vitamin K
      dependent gamma-carboxylation, was used in earlier work on adult zebrafish to
      provide evidence for the presence of vitamin K-dependent carboxylase in
      zebrafish. Here we demonstrate the presence of vitamin K-dependent carboxylase
      activity in zebrafish by directly assaying the microsomal fraction prepared from
      adult, unfertilized eggs, and embryos from different developmental stages. Gamma
      carboxylase activity was detected both before and after fertilization of embryos
      and the activity levels remained relatively constant from 6 h postfertilization
      (hpf) through other advanced stages of development. The expression of activity in
      the early embryos (0-6 hpf) may be due to the presence of maternal protein since
      the activity was detected even in the unfertilized eggs. Gamma-carboxylase
      activity in the eggs as well as early embryos suggested that vitamin K-dependent
      carboxylase is important throughout development. The detection of vitamin K
      dependent carboxylase mRNA by RT-PCR and inhibitor studies using warfarin
      confirmed these activity results. Further, these studies provide a basis for
      selecting warfarin-resistant zebrafish mutants in order to find genes regulating
      gamma-carboxylase activity including the yet unidentified vitamin K-epoxide
      reductase.

PMID- 11831866
TI  - Hematologically important mutations: leukocyte adhesion deficiency.
AB  - Leukocyte adhesion deficiency (LAD) is an immunodeficiency caused by defects in
      the adhesion of leukocytes (especially neutrophils) to the blood vessel wall. As
      a result, patients with LAD suffer from severe bacterial infections and impaired
      wound healing. In LAD-I, mutations are found in INTG2, the gene that encodes the
      beta subunit of the beta(2) integrins. In the rare LAD-II disease, the
      fucosylation of selectin ligands is disturbed, caused by mutations in the gene
      for a GDP-fucose transporter of the Golgi. This article summarizes all known
      patient mutations and polymorphisms in these genes.

PMID- 11831867
TI  - Dixon quantitative chemical shift imaging is a sensitive tool for the evaluation
      of bone marrow responses to individualized doses of enzyme supplementation
      therapy in type 1 Gaucher disease.
AB  - Type 1 Gaucher disease can be effectively treated with enzyme supplementation
      therapy. Bone disease is a debilitating feature of the disorder and results from
      infiltration of the bone marrow by Gaucher cells. The effect of treatment on bone
      marrow infiltration is difficult to measure, necessitating the development of
      sensitive techniques to allow adequate dosing. Dixon quantitative chemical shift
      imaging (Dixon-QCSI) is a MRI technique to measure displacement of fatty marrow
      by Gaucher cells. Low bone marrow fat fractions have been found in Gaucher
      disease. We studied the effect of individualized low doses of enzyme therapy on
      the fat fractions of the lumbar spine in 12 adult Gaucher disease patients before
      and during treatment and in 9 untreated Gaucher controls. Fat fractions were
      decreased in 9/12 patients (median 0.20, range 0.08-0.40) and equally low in the
      untreated Gaucher controls compared to age-matched healthy volunteers (normal
      values 0.27-0.43, P < 0.01). During treatment, fat fractions increased
      significantly already after 1 year in 11/12 patients (P = 0.007). After 4 to 5
      years, fat fractions normalized in 11/12 patients. Fat fractions remained low in
      the untreated Gaucher controls (P = 0.5 and 0.6 at 1 and 2 years, respectively).
      Six of 11 patients had a dose increase, which did not clearly affect fat
      fractions. Dixon-QCSI is a sensitive tool for the measurement of the response of
      bone marrow to enzyme therapy.

PMID- 11831868
TI  - Deformin, a substance found in Bartonella bacilliformis culture supernatants, is
      a small, hydrophobic molecule with an affinity for albumin.
AB  - Culture supernatants of Bartonella bacilliformis were previously shown to contain
      a factor, called deforming factor or deformin, which causes deformation and
      invagination of red cell membranes and formation of intracellular vacuoles. This
      factor is here shown to be a small water-soluble molecule, approximately 1400 Da
      as estimated by gel-filtration chromatography. Deforming factor binds tightly to
      albumin, especially albumin dimers and multimers, present in the growth medium.
      It can be released from albumin with 50% ethanol and has been partially purified
      by filtration and HPLC.

PMID- 11831869
TI  - The productivity and impact of the Leukemia & Lymphoma Society Scholar Program:
      the apparent positive effect of peer review.
AB  - A study was conducted to compare the "productivity" of a cohort of research grant
      applicants selected by peer review to be scholars of The Leukemia Society of
      America (now The Leukemia & Lymphoma Society) with a matched cohort of applicants
      not so selected during the period 1981 to 1990. One hundred and twenty-four
      scholars and 124 nonfunded applicants were studied. Two bibliometric variables
      and their derivatives were examined from the Institute of Scientific Information
      database: the number of papers published and the number of citations to those
      papers. Published papers were measured through December 31, 1999, and citation
      counts to these papers through December 31, 2000. Scholars published 10,301
      papers through the period of observation and nonfunded applicants published 6442
      papers. Scholars' papers were cited 536,283 [corrected] times, whereas nonfunded
      applicants' papers were cited 245,586 times. The mean citations per paper were 52
      for scholars and 38 for nonfunded applicants. The papers published per scholar,
      citations per scholar, and citations per paper per scholar were significantly
      greater than the corresponding measures for nonfunded applicants (P < 0.0001 in
      each case). Scholar's papers were cited 30% more often, whereas nonfunded
      applicants were cited 10% more frequently, than a comparison group of scientists
      publishing in the same journal in the same year. High-impact papers, e.g., papers
      that were cited more than 200 times, were nearly three times as frequent among
      scholars (494 papers) as among nonfunded applicants (173 papers). This difference
      was highly significant. The good (better than baseline) performance of nonfunded
      applicants may be a reflection of self-selection among the applicant pool for
      this competitive award; the more productive performance of the scholars is
      probably the result of the selection decisions made during the peer-review
      process.

PMID- 11831870
TI  - Characterization of endogenous Chinese hamster ovary cell surface molecules that
      mediate T cell costimulation.
AB  - Chinese hamster ovary (CHO) cells are commonly used in the generation of
      transfectants for use in in vitro costimulation assays. However, we have noted
      that nontransfected CHO cells can themselves provide a low-level B7/CD28
      independent costimulatory signal for CD3-mediated murine T cell activation and IL
      2 production. This study set out to identify those molecules that contribute to
      this CHO-dependent costimulatory activity. We describe a CHO subline capable of
      delivering potent CD28-independent costimulation to murine T cells and the
      generation of monoclonal antibodies against these CHO cells that inhibited this
      costimulatory activity. These blocking antibodies do not affect CHO cell
      independent costimulation or bind mouse cells, suggesting an effect mediated by
      their target molecules on the costimulatory competent CHO cells.
      Immunoprecipitation and expression cloning revealed that these antibodies bound
      the hamster homologues of Crry (CD21/35), CD44, CD54 (ICAM-1), CD63, CD87, CD147,
      and an 80- to 90-kDa protein which could not be cloned. Expression of these
      hamster genes on COS cells demonstrated that hamster CD54 was able to costimulate
      both CD3-mediated IL-2 secretion and T cell proliferation by naive murine T cells
      independent of the other molecules identified.

PMID- 11831871
TI  - Upregulation of decidual P-selectin expression is associated with an increased
      number of Th1 cell populations in patients suffering from spontaneous abortions.
AB  - A multicascade of leukocyte-endothelial cell interactions is involved in the
      trafficking of inflammatory lymphocytes into tissue. The primary contact between
      leukocytes and endothelium is mediated by selectins. Ligands for P-Selectin are
      preferentially expressed on Th1 cells and thereby allow migration of these
      inflammatory cells through the vessel wall. Since a peripheral and local Th1-type
      cytokine profile is present in spontaneous human abortion (SA), opposed by a Th2
      dominant situation in normal pregnancies (NP), we investigated (1) the phenotype
      of peripheral Th1 cells by flow cytometry, as well as the Th1-type cytokine
      levels by ELISA, (2) the decidual expression of P- and E-Selectin by
      immunohistochemistry (IHC), and (3) the phenotype of decidual immunocompetent
      cells by IHC in patients with NP or SA. We observed enhanced production of IFN
      gamma and TNF-alpha in CD8(+), CD3(+), and CD56(+) blood cells, as well as an
      increase in the number of CCR5(+) cells in patients suffering from SA compared to
      those with NP. No difference was detectable with respect to the serum levels of
      the two cytokines. Using IHC methods, we observed increased staining intensity of
      P-Selectin(+) vessels in samples of SA patients. E-Selectin was only weakly
      expressed in decidual endothelial cells, with no difference between NP and SA. In
      SA samples, E-Selectin(+) stromal cells were exclusively present. We further
      detected increased numbers of decidual CD8(+), CD3(+), CCR5(+), and CD56(+) cells
      in SA patients. We propose that Th1 lymphocyte migration into decidua is enhanced
      in SA due to upregulated P-Selectin expression in decidual vessels. This increase
      of Th1-producing lymphocytes might be involved in the rejection of trophoblasts.

PMID- 11831872
TI  - Involvement of ADAM9 in multinucleated giant cell formation of blood monocytes.
AB  - Monocytes-macrophages are converted to multinucleated giant cells by stimulation
      with various cytokines, and osteoclasts are the multinucleated giant cells
      derived from a monocyte-macrophage lineage. However, at present, the fusion
      peptides have not been clearly identified in monocytes-macrophages. The ADAM are
      a family of transmembrane glycoproteins that have a role in various biological
      functions. Interestingly, fertilin-alpha, ADAM9, and ADAM11 have potential fusion
      peptides. In this study, which ADAM was specifically expressed in monocytes
      stimulated with anti-CD98 antibody or RANKL and which factor(s) was functioning
      in monocytes as a fusion protein were investigated. ADAM1, 8, 10, 12, 15, 17, 20,
      and 21 mRNAs are expressed in blood monocytes incubated with control antibody,
      anti-FRP-1/CD98 antibody, or RANKL + M-CSF, while ADAM2, 7, 11, 13, 19, 23, 29,
      and 30 mRNAs could not be detected in these blood monocytes. Expression of ADAM9
      and ADAM10 mRNAs are enhanced by either RANKL + M-CSF or anti-CD98 antibody. The
      expression of ADAM9 and ADAM10 is also induced in blood monocytes by anti-CD98
      mAb. An anti-ADAM9 antibody enhances CD98-mediated cell aggregation, while it
      blocks CD98-mediated and RANKL-mediated multinucleated giant cell formation. A
      hydroxamate-based metalloprotease inhibitor, SI-27, which is found to suppress
      ADAM9 activity, suppresses multinucleated giant cell formation. New protein
      synthesis is necessary for the expression of ADAM9 mRNA and genistein suppresses
      induction of ADAM9 mRNA. This is the first report that ADAM9 is involved in
      monocyte fusion, such as CD98-mediated and RANKL-mediated cell fusion of blood
      monocytes. Furthermore, AMAM9 is one candidate for a fusion peptide in blood
      monocytes.

PMID- 11831874
TI  - Maintenance of NF-kappaB activation in T-lymphocytes and a naive T-cell
      population in autoimmune-prone (NZB/NZW)F(1) mice by feeding a food-restricted
      diet enriched with n-3 fatty acids.
AB  - We have previously shown that feeding a fish oil (FO) supplemented diet in
      combination with 40% food restriction (FO/FR) has a greater impact on extending
      life span in lupus-prone (NZB x NZW)F1 mice than either FO ad libitum (FO/AL) or
      corn oil food restricted (CO/FR) alone. Lupus disease is associated with
      increased Th-2 (i.e., IL-6 and IL-10) cytokine production and reduced IL-2
      production and NF-kappaB activation. We hypothesized that the mechanism of action
      by which FO/FR increases life span may involve alterations in T-lymphocyte
      signaling and subsequent cytokine production. To test this hypothesis, we
      isolated and then stimulated splenic T-lymphocytes ex vivo with anti-CD3 and 
      CD28 monoclonal antibodies. We report here that CO/FR and FO/FR and to a lesser
      extent FO/AL offset disease-associated losses in Th-1 cytokine production, CD69
      expression, and NF-kappaB activation in splenic T-lymphocytes activated ex vivo.
      Similarly, CO/FR and FO/FR prevented the disease-dependent rise in Th-2 cytokine
      production ex vivo and CD69 expression in vivo. In essence, the T-lymphocyte
      phenotype in the old CO/FR and FO/FR groups was identical to that in the young
      disease-free mice. Taken together, the data suggest that both CO/FR and FO/FR
      increase life span, in part, by maintaining a youthful immune phenotype in
      autoimmune-prone mice. However, FO/FR appears to represent a more potent dietary
      strategy in delaying disease-associated immune dysregulation than CO/FR.

PMID- 11831873
TI  - IL-13 transgene state impairs mycobacterial (type-1) and schistosomal (type-2)
      antigen-elicited responses.
AB  - Transgenic technology provides one approach for examining cytokine properties in
      vivo. This study directly tested the effect of a lung-targeted IL-13 transgene on
      the induction and elicitation of Th1 and Th2 cell-mediated immuno-inflammatory
      responses. Induction of Th1 (type 1) and Th2 (type 2) responses were tested by
      sensitization of IL-13 transgenics and littermates with purified protein
      derivative (PPD) of Mycobacterium bovis or Schistosoma mansoni eggs. Secondary
      elicitation of pulmonary granulomas was examined in adoptively sensitized
      transgenics and littermates challenged with bead-bound PPD or S. mansoni egg
      antigens. Parameters included lymphoid tissue cytokine profiles and granuloma
      sizes. Results showed that induction and elicitation of both type 1 and type 2
      cytokines and granulomas were significantly abrogated in transgenics. Systemic
      effects were possible, as transgenic serum contained high levels of circulating
      IL-13. These findings support the concept that IL-13 impairs effector functions
      and provide novel information regarding its role in regulating Th2 cytokines.

PMID- 11831875
TI  - Epithelial cells infected with respiratory syncytial virus are resistant to the
      anti-inflammatory effects of hydrocortisone.
AB  - In this work we continue our study of the biochemical responses of respiratory
      epithelial cells to infection with human paramyxovirus pathogens. In our earlier
      studies, we detected elevated concentrations of the proinflammatory chemokines
      MIP-1alpha and IL-8 in upper and lower respiratory tract secretions from patients
      infected with respiratory syncytial virus (RSV). Here we demonstrate the same
      trend for individuals infected with parainfluenza virus (PIV), with elevated
      concentrations of MIP-1alpha and IL-8 (means of 309 +/- 51 and 2280 +/- 440
      pg/ml/mg protein, respectively) detected in nasal wash samples from 17 patients
      with culture-positive PIV. Similar to our findings with RSV, cells of the HEp-2
      epithelial line and primary cultures of human bronchial epithelial cells respond
      to PIV infection with production and release of both MIP-1alpha and IL-8.
      Addition of the glucocorticoid anti-inflammatory agent hydrocortisone (200-1000
      ng/ml) attenuated the production of MIP-1alpha and IL-8 in PIV-infected cells
      while having minimal to no effect on the production of these mediators from cells
      infected with RSV. Neither virus infection resulted in a change in the total
      cellular concentration of glucocorticoid receptors, nor did hydrocortisone exert
      any differential effect on viral replication. As repression of chemokine
      production by epithelial cells is likely to result in diminished recruitment of
      proinflammatory leukocytes, these results may explain in part why glucocorticoid
      therapy reduces the symptoms associated with acute PIV infection, but have little
      to no effect in the overall outcome in the case of RSV.

PMID- 11831878
TI  - High-throughput screening system for catalytic hydrogen-producing materials.
AB  - A high-throughput screening system and methodology were developed for libraries
      of hydrogen (H(2)) producing catalytic materials. The system is based on the
      chemo-optical properties of WO(3), which give rise to reflectance changes in the
      presence of H(2). Pd-coated WO(3) sensors were synthesized and examined for their
      hydrogen sensitivity, wavelength-dependent reflectance, and performance in the
      presence of water vapor. For high-throughput screening, a polypropylene reactor
      block was designed and constructed to house 8 x 12 catalyst libraries deposited
      as thin films. When the library and reactor block are assembled together, 96
      independent microreactor units are formed. A large-area Pd/WO(3) sensor film
      covers and seals all microreactors, forming a 96-element 2-D H(2) sensor array.
      As H(2) is produced differentially across the library, the reflectance changes of
      the Pd/WO(3) film are monitored by reflectivity sensors that scan the surface
      every 30 s. The time-dependent changes in reflectance indicate relative rates of
      H(2) production. A library of cathode electrocatalysts was synthesized from Ti,
      Pt, Ni, Au, Pd, Al, Ag, Ge, and mixtures thereof to demonstrate the H(2) high
      throughput screening system. The results of the electrolytic screening are in
      agreement with expected literature trends: mixtures of Ni and samples containing
      Pt and Pd generated H(2) at the greatest rates, while Ge- and Ti-based materials
      were the least effective electrocatalysts. A mixture of 80% Al and 20% Pt was
      found to have the highest rate of H(2) production. This high-throughput screening
      system is applicable in a variety of catalytic screening applications where
      hydrogen is the desired product.

PMID- 11831876
TI  - The FX enzyme is a functional component of lymphocyte activation.
AB  - Fucose is an essential constituent of selectin ligands. These molecules mediate
      the initial contact between extravasating leukocytes and endothelial cells. The
      generation of GDP-L-fucose by the FX enzyme is the final step of fucose
      biosynthesis. Recently, we demonstrated that outside-in signaling regulates the
      expression of the FX enzyme in certain cancer cells. The present study
      demonstrates that the polyclonal activation of T and B cells significantly up
      regulated the expression of the FX enzyme and of the fucosylated selectin ligands
      sLe-x and CLA. Treatment of T cells with FX antisense oligonucleotides
      significantly decreased selectin ligand expression upon activation. We conclude
      that FX is regulated by outside-in signals also in lymphocytes and that this
      enzyme is involved in the biosynthesis of selectin ligands in such cells. We
      propose that FX takes part in the cascade of events leading to the extravasation
      of activated lymphocytes.

PMID- 11831877
TI  - Participation of Vbeta13(+) and Vbeta1(+) T cells in transfer thyroiditis after
      activation of mouse thyroglobulin-primed T cells by superantigen staphylococcal
      enterotoxin A.
AB  - Murine experimental autoimmune thyroiditis (EAT) is a T-cell-mediated disease,
      but the T cell receptor (TCR) Vbeta gene usage in pathogenesis has not been well
      delineated. One approach is to utilize bacterial superantigens, such as
      staphylococcal enterotoxin (SE) A and B, to stimulate known sets of TCR Vbeta
      families in mouse thyroglobulin (mTg)-primed cells for thyroiditis transfer. Our
      previous use of SEB to activate mTg-primed cells led to no thyroiditis transfer,
      despite a major increase in Vbeta8(+) T cells. Unlike SEB, SEA activation did
      transfer thyroiditis. To determine which thyroiditogenic Vbeta(+) T cells were
      involved, SEA-activated T cells have now been analyzed. After repeated SEA
      activation in vitro, both mTg-reactive and thyroiditogenic cells persisted. FACS
      analysis indicated that most Vbeta13(+) cells were "large" cells (IL-2R(+)) and
      expressed the activation marker, transferrin receptor (CD71). RT-PCR analysis
      also showed the presence of both Vbeta13(+) and SEA-reactive Vbeta1(+) cells.
      Since our previous analyses by RT-PCR of the thyroid infiltrate after either
      induction or adoptive transfer have implicated both Vbeta13(+) and Vbeta1(+)
      cells, their activation by SEA to transfer thyroiditis further supports their
      role.

PMID- 11831879
TI  - Design, synthesis, and biological evaluation of a library of 1-(2-thiazolyl)-5
      (trifluoromethyl)pyrazole-4-carboxamides.
AB  - A library of 422 1-(2-thiazolyl)-5-(trifluoromethyl)pyrazole-4-carboxamides was
      prepared in five steps using solution-phase chemistry. The first step in the
      synthesis was the reaction of ethyl 2-ethoxymethylene-3-oxo-4,4,4
      trifluorobutanoate with thiosemicarbazide, which is reported in the literature to
      afford a 1:1 mixture of ethyl 1-thiocarbamoyl-5-(trifluoromethyl)pyrazole-4
      carboxylate and ethyl 1-thiocarbamoyl-3-(trifluoromethyl)pyrazole-4-carboxylate.
      We reassigned the structure of the product to be a single compound, ethyl 5
      hydroxy-1-thiocarbamoyl-5-(trifluoromethyl)-4,5-dihydro-1H-pyrazole-4
      carboxylate. This common intermediate was diversified by reaction with 17 alpha
      bromoketones affording, in two steps, 17 1-(2-thiazolyl)-5
      (trifluoromethyl)pyrazole-4-carboxylic acids. Scavenger resins were used to
      facilitate formation and purification of up to 27 amides from each of these acids
      in the last step. In addition, the Curtius reaction was applied to 12 of the
      acids followed by quenching with alcohols to afford a 108-member carbamate
      library. Certain compounds in the two libraries were toxic to C. elegans.

PMID- 11831880
TI  - A general method for the solid-phase synthesis of unsymmetrical tri- and
      tetrasubstituted ureas.
AB  - A general method for the preparation of unsymmetrical di, tri-, and
      tetrasubstituted ureas on polymer supports is presented. Polymer-bound primary
      and secondary amines react with imidazolium salts (urea donors), which are
      generated from the reaction of N,N'-carbonyldiimidazole (CDI) with primary and
      secondary amines followed by alkylation with MeI to give tri- and
      tetrasubstituted ureas in excellent yields (76-98%) and purities (80-99%).

PMID- 11831881
TI  - Studies on the chemical stability and functional group compatibility of the
      benzoin photolabile safety-catch linker using an analytical construct.
AB  - A chemical stability study of the benzoin photolabile safety-catch linker (BPSC)
      has been carried out using a dual-linker analytical construct to establish its
      compatibility with a range of commonly employed solid-phase reaction conditions.
      As a result of this study, the dithiane-protected benzoin linker was shown to be
      reactive only toward strong acids and fluoride nucleophile. Furthermore, a scan
      of diverse functional groups thought to be unstable toward the safety-catch
      removal conditions has also been carried out. These data should provide
      assistance in future utilization of the BPSC for syntheses.

PMID- 11831882
TI  - Polymer-supported approach for solution-phase synthesis of cysteine trap protease
      inhibitors: procedure for straightforward optimization of the P1-P1' pocket.
AB  - Peptide-based reversible and irreversible cysteine proteases inhibitors are well
      reported in the literature. Many of these compounds have an electrophilic
      carbonyl group as a cysteine trap in the place of a scissile amide moiety of the
      natural substrate. As a common mechanism strategy, we have designed a probe
      library of a cysteine trap for rapid optimization of P1-P1' pockets of different
      cysteine proteases. The synthesis of this library using a straightforward
      methodology based on polymer-supported reagents and scavengers to avoid tedious
      purification steps has been achieved. For the selective monobromination of diazo
      ketones, preparation of a new supported reagent, piperidinoaminomethylpolystyrene
      hydrobromide, is also described.

PMID- 11831883
TI  - Combinatorial synthesis of natural product-like molecules using a first
      generation spiroketal scaffold.
AB  - Recently, significant attention has been focused on the synthesis small-molecule
      libraries based on natural product or natural product-like structures. In this
      paper, we report our initial studies on the use of the 1,7
      dioxaspiro[5,5]undecane (spiroketal) moiety as a rigid-core template for
      elaboration using parallel synthesis techniques. The synthesis of a spiroketal
      scaffold that is reminiscent of the spiroketal subunits found in the spiroketal
      macrolide antibiotics will be described. Elaboration of three independently
      addressable functional groups on the scaffold using solution-phase parallel
      synthesis techniques led to the preparation of a small library of natural product
      like compounds. These studies pave the way for evaluation of highly
      functionalized spiroketals in phenotypic assays and as prospective antagonists of
      protein-protein interactions.

PMID- 11831884
TI  - Solid-phase preparation of hydantoins through a new cyclization/cleavage step.
AB  - An efficient process for the solid-phase synthesis of hydantoins has been
      developed. The amino acid starting material is anchored to the resin from its
      carboxylic acid end through formation of a very stable amide bond. After
      introduction of different functional groups, the cleavage/cyclization step can be
      performed in acidic or basic conditions.

PMID- 11831885
TI  - Mass spectrometric sequencing of individual peptides from combinatorial libraries
      via specific generation of chain-terminated sequences.
AB  - Combinatorial peptide libraries are a versatile tool for drug discovery. On-bead
      assays identify reactive peptides by enzyme-catalyzed staining and, usually,
      sequencing by Edman degradation. Unfortunately, the latter method is expensive
      and time-consuming and requires free N termini of the peptides. A method of rapid
      and unambiguous peptide sequencing by utilizing synthesis-implemented generation
      of termination sequences with subsequent matrix-assisted laser desorption
      ionization time of flight (MALDI-TOF) mass spectrometric analysis is introduced
      here. The required capped sequences are determined and optimized for a specific
      peptide library by a computer algorithm implemented in the program Biblio. A
      total of 99.7% of the sequences of a heptapeptide library sample could be decoded
      utilizing a single bead for each spectrum. To synthesize these libraries, an
      optimized capping approach has been introduced.

PMID- 11831886
TI  - Microwave parallel library generation: comparison of a conventional- and
      microwave-generated substituted 4(5)-sulfanyl-1H-imidazole library.
AB  - A methodology for the microwave parallel synthesis of libraries is described. The
      procedure involves the use of an array of expandable reaction vessels, which can
      accommodate pressure buildup within the vessel due to heating without loss of
      volatile solvents or reagents. A demonstration 24-membered library of substituted
      4(5)-sulfanyl-1H-imidazoles was generated by both conventional and microwave
      procedures, achieving a reduction from 12 h to 16 min in library generation time
      for the microwave approach.

PMID- 11831887
TI  - Inhibitors of human histone deacetylase: synthesis and enzyme and cellular
      activity of straight chain hydroxamates.
AB  - Inhibitors of histone deacetylase (HDAC) have been shown to induce terminal
      differentiation of human tumor cell lines and to have antitumor effects in vivo.
      We have prepared analogues of suberoylanilide hydroxamic acid (SAHA) and
      trichostatin A and have evaluated them in a human HDAC enzyme inhibition assay, a
      p21(waf1) (p21) promoter assay, and in monolayer growth inhibition assays. One
      compound, 4-(dimethylamino)-N-[7-(hydroxyamino)-7-oxoheptyl]-benzamide, was found
      to affect the growth of a panel of eight human tumor cell lines differentially.

PMID- 11831888
TI  - DNA cleavage potency, cytotoxicity, and mechanism of action of a novel class of
      enediyne prodrugs.
AB  - We have discovered a novel class of (E)-3-acyloxy-4-(arylmethylidene)cyclodeca
      1,5-diynes which exhibit promising enediyne-like DNA cleavage and cytotoxic
      activities. LC-MS analysis of the incubation mixture (pH 8.5, 37 degrees C)
      confirmed formation of 10-membered ring enediyne presumably via an allylic cation
      and suggested that the 1,4-benzenoid diradical might be one of the active species
      for DNA damage and cytotoxicity.

PMID- 11831889
TI  - Environmental mimic of receptor interaction: conformational analysis of CCK-15 in
      solution.
AB  - CCK-15, a peptide derived from the 115-membered CCK preprohormone, was the object
      of a comparative conformational analysis by NMR spectroscopy and molecular
      modeling methods. NMR data in several solvents demonstrate that the propensity of
      the peptide to fold into a helical conformation is intrinsic, not merely a
      consequence of the interaction with phosphatidylcholine micelles or with a
      putative receptor, as suggested by a previous study on CCK-8 (Pellegrini, M.;
      Mierke, D. Biochemistry 1999, 38, 14775-14783.). The prevailing CCK-15 conformer
      in a mixture 1,1,1,3,3,3-hexafluoroacetone/water reveals that the residues common
      to CCK-15 and CCK-8 assume very similar conformations. Our CCK-15 structure is
      consistent with the model of receptor interaction proposed by Pellegrini and
      Mierke and discloses possible novel interactions that involve a larger area of
      the putative receptor. The consensus structure between CCK-15 and CCK-8 shows a
      good superposition of the side chains of residues 12-14 with crucial moieties of
      two non-peptidic CCK-A antagonists.

PMID- 11831890
TI  - Synthesis, biological activity, and molecular modeling investigation of new
      pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine derivatives as human A(3)
      adenosine receptor antagonists.
AB  - A new series of pyrazolotriazolopyrimidines bearing different substitutions on
      the phenylcarbamoyl moieties at the N5 position, being highly potent and
      selective human A(3) adenosine receptor antagonists, is described. The compounds
      represent an extension and an improvement of our previous work on this class of
      compounds (J. Med. Chem. 1999, 42, 4473-4478; J. Med. Chem. 2000, 43, 4768-4780).
      All the synthesized compounds showed A(3) adenosine receptor affinity in the
      subnanomolar range and high levels of selectivity in radioligand binding assays
      at the human A(1), A(2A), A(2B), and A(3) adenosine receptors. In particular, the
      effect of the substitution and its position on the phenyl ring have been studied.
      From binding data, it is evident that the unsubstituted derivatives on the phenyl
      ring (e.g., compound 59, hA(3) = 0.16 nM, hA(1)/hA(3) = 3713, hA(2A)/hA(3) =
      2381, hA(2B)/hA(3) = 1388) showed the best profile in terms of affinity and
      selectivity at the human A(3) adenosine receptors. The introduction of a sulfonic
      acid moiety at the para position on the phenyl ring was attempted in order to
      design water soluble derivatives. However, this substitution led to a dramatic
      decrease of affinity at all four adenosine receptor subtypes. A computer
      generated model of the human A(3) receptor was built and analyzed to better
      interpret these results, demonstrating that steric control, in particular at the
      para position on the phenyl ring, plays a fundamental role in the receptor
      interaction. Some of the synthesized compounds proved to be full antagonists in a
      specific functional model, where the inhibition of cAMP-generation by IB-MECA was
      measured in membranes of CHO cells stably transfected with the human A(3)
      receptor with IC(50) values in the nanomolar range, with a statistically
      significative linear relationship with the binding data.

PMID- 11831891
TI  - A three-dimensional quantitative structure-activity relationship study of heparin
      binding epidermal growth factor shedding inhibitors using comparative molecular
      field analysis.
AB  - Despite the lack of structural information on the heparin-binding (HB) epidermal
      growth factor (EGF) shedding putative target enzyme, the design of potent HB-EGF
      shedding inhibitors has been attempted by means of comparative molecular field
      analysis (CoMFA), a well-established 3D-QSAR technique. Two different binding
      modes, obtained by docking a flexible representative into the MMP-3 and TACE
      target enzymes, were considered as alignment rules for an in-house data set of 50
      HB-EGF shedding inhibitors. CoMFA models were derived with the standard steric,
      electrostatic, and Bohacek and McMartin's H-bond molecular fields. These fields
      were used individually or in combination. For both alignments, the H-bond field
      alone yielded the best statistical models. From the analysis of the CoMFA
      contours, ideas for testing the size of the S1' pocket and suggestions for the
      design of new inhibitors came forward, resulting in the synthesis and testing of
      four new inhibitors. Three of four compounds turned out to possess from good
      (IC(50) = 0.56 and 0.60 microM) to excellent (IC(50) = 0.13 microM) inhibitory
      activity. The hypothesis that, upon binding, the S1' pocket in the vicinity of
      the R(1) benzene ring must be narrow in size was confirmed by the weak activity
      (IC(50) = 1.1 microM) of the fourth compound. The experimental profile of these
      new inhibitors does suggest the MMP-3 alignment as the most plausible one for HB
      EGF shedding inhibitors.

PMID- 11831892
TI  - Novel tricyclic-alpha-alkyloxyphenylpropionic acids: dual PPARalpha/gamma
      agonists with hypolipidemic and antidiabetic activity.
AB  - Synthesis and structure-activity relationships of tricyclic alpha-ethoxy
      phenylpropionic acid derivatives guided by in vitro PPARalpha and PPARgamma
      transactivation data and computer modeling led to the identification of the novel
      carbazole analogue, 3q, with dual PPARalpha (EC(50) = 0.36 microM) and PPARgamma
      (EC(50) = 0.17 microM) activity in vitro. Ten days treatment of db/db mice with
      3q improved the insulin sensitivity, as measured by OGTT, better than that seen
      with both pioglitazone and rosiglitazone treatment, suggesting in vivo PPARgamma
      activity. Likewise, 3q lowered plasma triglycerides and cholesterol in high
      cholesterol fed rats after 4 days treatment, indicating in vivo PPARalpha
      activity. Investigations of the pharmacokinetics of selected compounds suggested
      that extended drug exposure improved the in vivo activity of in vitro active
      compounds.

PMID- 11831893
TI  - Minor groove DNA binders as antimicrobial agents. 1. Pyrrole tetraamides are
      potent antibacterials against vancomycin resistant Enterococci [corrected] and
      methicillin resistant Staphylococcus aureus.
AB  - A new series of short pyrrole tetraamides are described whose submicromolar DNA
      binding affinity is an essential component for their strong antibacterial
      activity. This class of compounds is related to the linked bis-netropsins and bis
      distamycins, but here, only one amino-pyrrole-carboxamide unit and an amidine
      tail is connected to either side of a central dicarboxylic acid linker. The
      highest degree of DNA binding, measured by compound-induced changes in UV melting
      temperatures of an AT-rich DNA oligomer, was observed for flat, aromatic linkers
      with no inherent bent, i.e., terephthalic acid or 1,4-pyridine-dicarboxylic acid.
      However, the antibacterial activity is critically linked to the size of the N
      alkyl substiutent of the pyrrole unit. None of the tetraamides with the commonly
      used methyl-pyrrole showed antibacterial activity. Isoamyl- or
      cyclopropylmethylene-substituted dipyrrole derivatives have the minimum
      inhibitory concentrations in the submicromolar range. In vitro toxicity against
      human T-cells was studied for all compounds. The degree to which compounds
      inhibited cell growth was neither directly correlated to DNA binding affinity nor
      directly correlated to antibacterial activity but seemed to depend strongly on
      the nature of the N-alkyl pyrrole substituents.

PMID- 11831894
TI  - Mining the National Cancer Institute's tumor-screening database: identification
      of compounds with similar cellular activities.
AB  - In an effort to enhance access to information available in the National Cancer
      Institute's (NCI) anticancer drug-screening database, a new suite of Internet
      accessible (http://spheroid. ncifcrf.gov) computational tools has been assembled
      for self-organizing map-based (SOM) cluster analysis and data visualization. A
      range of analysis questions were initially addressed to evaluate improvements in
      SOM cluster quality based on the data-conditioning procedures of Z-score
      normalization, capping, and treatment of missing data as well as completeness of
      drug cell-screening data. These studies established a foundation for SOM cluster
      analysis of the complete set of NCI's publicly available antitumor drug-screening
      data. This analysis identified relationships between chemotypes of screened
      agents and their effect on four major classes of cellular activities: mitosis,
      nucleic acid synthesis, membrane transport and integrity, and phosphatase- and
      kinase-mediated cell cycle regulation. Validations of these cellular activities,
      obtained from literature sources, found (i) strong evidence supporting within
      cluster memberships and shared cellular activity, (ii) indications of compound
      selectivity between various types of cellular activity, and (iii) strengths and
      weaknesses of the NCI's antitumor drug screen data for assigning compounds to
      these classes of cellular activity. Subsequent analyses of averaged responses
      within these tumor panel types find a strong dependence on chemotype for
      coherence among cellular response patterns. The advantages of a global analysis
      of the complete screening data set are discussed.

PMID- 11831895
TI  - CoMFA and CoMSIA 3D QSAR and docking studies on conformationally-restrained
      cinnamoyl HIV-1 integrase inhibitors: exploration of a binding mode at the active
      site.
AB  - Anti-HIV (human immunodeficiency virus) drug discovery has been increasingly
      focusing on HIV integrase (IN) as a potential therapeutic target. This enzyme is
      required for the integration of reverse transcribed proviral DNA into the host
      cell's genome and is essential for the propagation of the HIV life cycle.
      Comparative molecular field analysis (CoMFA) and comparative molecular similarity
      indices analysis (CoMSIA) three-dimensional quantitative structure-activity
      relationship (3D QSAR) studies and docking simulations were conducted on a series
      of potent conformationally restrained cinnamoyl inhibitors of HIV-1 IN (Artico;
      et al. J. Med. Chem. 1998, 41, 3948-3960). Predictive 3D QSAR models were
      established using SYBYL multifit molecular alignment rule, which had conventional
      r(2) and cross-validated coeffiecient (q(2)) values up to 0.981 and 0.721 for
      CoMFA and 0.975 and 0.804 for CoMSIA, respectively. These models were validated
      by an external test set (Burke; et al. J. Med. Chem. 1995, 38, 4171-4178). CoMFA
      and CoMSIA 3D QSAR models were also derived using a molecular alignment obtained
      by docking the compounds into the active site of HIV IN. These latter models were
      comparable to multifit-derived models in terms of relative descriptor field
      contributions and the partial least squares (PLS) contour maps. The CoMSIA 3D
      QSAR models performed better than the CoMFA models. The superior performance of
      CoMSIA was attributed to the large contribution of hydrogen-bonding interactions
      to the inhibitory activity differences among the compounds. This was supported by
      FlexX binding energy scores that correlated well with the inhibitory activity
      differences between hydroxylated compounds and their corresponding methoxy or
      deoxy counterparts. The CoMFA and CoMSIA PLS contour maps and MOLCAD-generated
      active site electrostatic, lipophilicity, and hydrogen-bonding potential surface
      maps, as well as the docking results, were integrated to propose a binding mode
      for the cinnamoyl inhibitors at the active site of HIV-1 IN.

PMID- 11831896
TI  - Structural basis of RasGRP binding to high-affinity PKC ligands.
AB  - The Ras guanyl releasing protein RasGRP belongs to the CDC25 class of guanyl
      nucleotide exchange factors that regulate Ras-related GTPases. These GTPases
      serve as switches for the propagation and divergence of signaling pathways. One
      interesting feature of RasGRP is the presence of a C-terminal C1 domain, which
      has high homology to the PKC C1 domain and binds to diacylglycerol (DAG) and
      phorbol esters. RasGRP thus represents a novel, non-kinase phorbol ester
      receptor. In this paper, we investigate the binding of indolactam(V) (ILV), 7-(n
      octyl)-ILV, 8-(1-decynyl)benzolactam(V) (benzolactam), and 7-methoxy-8-(1
      decynyl)benzolactam(V) (methoxylated benzolactam) to RasGRP through both
      experimental binding assays and molecular modeling studies. The binding
      affinities of these lactams to RasGRP are within the nanomolar range. Homology
      modeling was used to model the structure of the RasGRP C1 domain (C1-RasGRP),
      which was subsequently used to model the structures of C1-RasGRP in complex with
      these ligands and phorbol 13-acetate using a computational docking method. The
      structural model of C1-RasGRP exhibits a folding pattern that is nearly identical
      to that of C1b-PKCdelta and is comprised of three antiparallel-strand beta-sheets
      capped against a C-terminal alpha-helix. Two loops A and B comprising residues 8
      12 and 21-27 form a binding pocket that has some positive charge character. The
      ligands phorbol 13-acetate, benzolactam, and ILV are recognized by C1-RasGRP
      through a number of hydrogen bonds with loops A and B. In the models of C1-RasGRP
      in complex with phorbol 13-acetate, benzolactam, and ILV, common hydrogen bonds
      are formed with two residues Thr12 and Leu21, whereas other hydrogen bond
      interactions are unique for each ligand. Furthermore, our modeling results
      suggest that the shallower insertion of ligands into the binding pocket of C1
      RasGRP compared to C1b-PKCdelta may be due to the presence of Phe rather than Leu
      at position 20 in C1-RasGRP. Taken together, our experimental and modeling
      studies provide us with a better understanding of the structural basis of the
      binding of PKC ligands to the novel phorbol ester receptor RasGRP.

PMID- 11831897
TI  - DNA cross-linking by azinomycin B: Monte Carlo simulations in the evaluation of
      sequence selectivity.
AB  - A new set of charges specifically developed for biologically relevant N7
      alkylated purine adducts have been implemented in the AMBER force field of the
      MacroModel package and applied to the conformational search of azinomycin B-DNA
      interactions. To perform a sequence dependent reactivity relationship study, four
      DNA triplets known to interact differently with the drug, 5'-GCT-3', 5'-GCC-3',
      5'-GTC-3', and 5'-GTT-3', have been modeled in B-form and intercalative
      conformations. Monte Carlo simulations of all possible monoadducts and
      intercalative complexes have been carried out and analyzed using a filtering
      criterion that estimates the probability of covalent bond formation and covalent
      cross-linking. We observed a good correlation between existing experimental data
      and our computational estimations that validate the approach. The comparison of
      the conformational properties of the drug-DNA monoadducts and complexes confirms
      the most probable mechanism of action involving an initial aziridine and
      subsequent epoxide alkylation. The different hydrogen bond network in the
      monoadducts and in the intercalative complexes between the drug and the three
      base-pair receptor is the primary reason for the different cross-linking
      reactivity. In addition, steric hindrance of the major groove exposed methyl
      group of central thymine-based triplets plays an important role in the lack of
      the reactivity of these sequences. Synthetic work on the azinomycins and the
      information coming from this computational study will be important for the design
      of more potent or DNA sequence-selective agents based on the azinomycin skeleton.

PMID- 11831898
TI  - A 3.(ET743)-DNA complex that both resembles an RNA-DNA hybrid and mimicks zinc
      finger-induced DNA structural distortions.
AB  - The antitumor ecteinascidin ET743 has been shown to inhibit the transcriptional
      activation of a number of genes at nanomolar concentrations. Cell sensitivity to
      subnanomolar concentrations of the drug has also been shown to specifically
      depend on the transcription-coupled nucleotide excision repair system. ET743 is
      known to bind covalently to the minor groove of a DNA double helix in regions
      comprising selected sets of three consecutive base pairs. Following alkylation of
      a central guanine, the minor groove is widened and the DNA is bent toward the
      major groove. We have previously shown that in the resulting adduct the DNA
      triplet containing the covalently modified guanine bears a strong resemblance to
      a DNA triplet recognized by a C(2)H(2) zinc finger. We now expand this earlier
      finding and use simulation methods to show that head-to-tail binding of three
      ET743 molecules to three adjacent optimal binding sites stabilizes a DNA
      structure whose conformation is intermediate between A- and B-form DNA.
      Furthermore, despite the increase in roll at the sites of covalent attachment, no
      net curvature is apparent in this complex due to cancellation of the localized
      bends over virtually one turn of the helix. Both observations are in good analogy
      to findings in zinc finger-DNA complexes. Triplets are virtually superimposable
      both directly and upon shifting the register one base pair. In this latter case,
      the central guanine in a triplet alkylated by ET743 corresponds to the third
      nucleic base in the triplet recognized by a zinc finger of transcription factors
      such as EGR1 or Sp-1. The DNA conformation found in the ET743-DNA complex is also
      strongly reminiscent of an RNA-DNA hybrid, as found in the RNA polymerase II
      elongation complex. The possible biological implications of these findings in
      relation to the antitumor action of ET743 are discussed.

PMID- 11831899
TI  - Designing analogues of mini atrial natriuretic peptide based on structural
      analysis by NMR and restrained molecular dynamics.
AB  - Analogues of mini atrial natriuretic peptide (miniANP) that provide
      conformational properties related to biological activity were designed on the
      basis of the structure revealed by NMR and restrained molecular dynamics (rMD)
      simulation, and an analogue with a high level of biological activity was
      successfully obtained. MiniANP is a cyclic pentadecapeptide analogue of atrial
      natriuretic polypeptide (ANP). The conformation of miniANP analyzed by NMR and
      rMD simulation indicated that positive phi angles are preferred for Gly(5) and
      Gly(6), which is typical for D-amino acids. On the basis of the structural
      information, [D-Ala(5)]miniANP, [D-Ala(6)]miniANP, and [D-Ala(5) D-Ala(6)]miniANP
      were synthesized. The biological activity of [D-Ala(5)]miniANP was stronger than
      that of miniANP, confirming that Gly(5) of miniANP takes a positive phi angle on
      binding to the receptor. Conformational analysis of these analogue peptides by
      NMR suggested that a turnlike conformation at residues 6-9 and a proximate pair
      formed by side chains of Phe(4) and Ile(11) are important for the biological
      activity.

PMID- 11831900
TI  - Structural aspects of isozyme selectivity in the binding of inhibitors to
      carbonic anhydrases II and IV.
AB  - Carbonic anhydrase inhibitors are effective in lowering intraocular pressure, the
      primary indication of glaucoma. Human carbonic anhydrase II, and possibly
      carbonic anhydrase IV (CAII and CAIV, respectively), help regulate fluid
      secretion into the anterior chamber of the eye. Because inhibitors currently
      formulated as drugs to treat glaucoma were designed to target CAII, an
      understanding of the structural basis of CAII-CAIV discrimination by inhibitors
      would be useful for probing the role of each isozyme in the etiology of the
      disease. Here, we report the X-ray crystal structures of three novel thieno[3,2
      e]-1,2-thiazine-6-sulfonamides complexed with CAII and the computationally
      predicted structures of the same compounds complexed with CAIV. All three
      compounds bind with similar affinity to CAII, but they bind with up to 100-fold
      lower affinities to CAIV. Comparisons of experimentally determined structures of
      CAII-inhibitor complexes and computationally predicted structures of CAIV
      inhibitor complexes allow us to rationalize these affinity trends and outline
      molecular features that may contribute to high-affinity inhibitor binding to
      CAIV. This study demonstrates how experimental structure determination methods
      and computational structure prediction methods can be used together to answer
      questions that cannot be answered by either method alone.

PMID- 11831901
TI  - Kinetic studies of the binding of acridinecarboxamide topoisomerase poisons to
      DNA: implications for mode of binding of ligands with uncharged chromophores.
AB  - We have used stopped-flow spectrophotometry and the sodium dodecyl sulfate
      sequestration technique to study the kinetics of dissociation of DNA complexes of
      the mixed topoisomerase I/II poison N-[2-(dimethylamino)ethyl]acridine-4
      carboxamide (termed DACA) and a range of related linear tricyclic carboxamides
      with neutral chromophores. Complexes of DACA and related acridine and
      phenazinecarboxamides bearing an N,N-dimethylaminoethyl side chain dissociate
      from calf thymus DNA by a kinetic pathway involving four discernible steps in a
      manner similar to complexes of N-[(2-dimethylamino)ethyl]-9-aminoacridine-4
      carboxamide (termed 9-amino-DACA). We infer from these findings that the side
      chains of DACA, its phenazine homologue, and 9-amino-DACA make comparable
      interactions with the DNA base pairs. In the case of 9-amino-DACA, a selective
      topoisomerase II poison, these are known, by crystallographic analysis, to
      involve hydrogen-bonding interactions between the protonated dimethylammonium
      group of the side chain and the O6/N7 atoms of guanine and to include a bridging
      water molecule hydrogen bonded to the carboxamide group and a phosphate oxygen.
      By contrast, we find that other linear tricyclic carboxamides with neutral
      chromophores which lack a peri nitrogen atom and are biologically inactive
      dissociate from DNA by a different mechanism in which it appears their side
      chains fail to interact with guanine. We conclude that the ability of the
      carboxamide group to lie preferentially in the plane of the chromophore, so
      facilitating the dimethylammonium-guanine hydrogen bond and ensuring maintenance
      of the water-bridged carboxamide-phosphate interaction, is a critical requirement
      for antitumor activity among ligands of the linear tricyclic carboxamide class.
      However, unlike the situation for 9-amino-DACA, for ligands with uncharged
      chromophores containing peri nitrogen atoms such as DACA, this outcome is
      possible with the 4-carboxamide group rotated cis or trans with respect to the
      ring nitrogen. This difference may have relevance to the ability of DACA to be a
      dual poison of both topoisomerases I and II.

PMID- 11831902
TI  - Pyridophens: binary pyridostigmine-aprophen prodrugs with differential inhibition
      of acetylcholinesterase, butyrylcholinesterase, and muscarinic receptors.
AB  - A series of "binary prodrugs" called carbaphens,(1) carbamylated derivatives on
      one or both of the aromatic rings of the muscarinic receptor antagonist aprophen
      [(N,N-diethylamino)ethyl 2,2-diphenylpropionate], were synthesized to develop
      binary prophylactic agents against organophosphorus intoxication. As a group, the
      carbaphens retained the muscarinic receptor antagonist properties of aprophen but
      also preferentially inhibited butyrylcholinesterase (BChE) in contrast to
      acetylcholinesterase (AChE). Therefore, a new series of compounds named
      pyridophens were designed and synthesized to achieve binary prodrugs to
      preferentially inhibit AChE over BChE, while still retaining the muscarinic
      receptor antagonism of aprophen. The pyridophens consist of the basic
      pyridostigmine skeleton combined with the 2,2-diphenylpropionate portion of
      aprophen by replacement of the diethylamino group. Three compounds, 9 (a tertiary
      pyridine), 10 (a quaternary pyridine), and 12 (a tertiary tetrahydropyridine),
      were found to be effective inhibitors of both BChE and AChE. However, 10, N
      methyl-3-[[(dimethylamino)carbonyl]oxy]-2-(2'2'-diphenylpropionoxy
      methyl)pyridinium iodide, inhibited AChE selectively over BChE, with a
      bimolecular rate constant similar to pyridostigmine. In contrast to their potent
      cholinesterase inhibitory activity, all of the pyridophen analogues were less
      potent antagonists of the muscarinic receptor than aprophen.

PMID- 11831903
TI  - Cysteine derivatives as inhibitors for carboxypeptidase A: synthesis and
      structure-activity relationships.
AB  - A series of cysteine (Cys) derivatives having an alkyl or arylalkyl moiety on the
      alpha-amino group of the amino acid have been synthesized as a novel type of
      inhibitor for carboxypeptidase A. These compounds are readily prepared starting
      with Cys in an optically active form. The structure-activity relationship study
      revealed that the inhibitors prepared from D-Cys are much more potent than the
      corresponding inhibitors obtained from L-Cys, and the most potent inhibitor in
      the series, (S)-1j with a K(i) value of 55 +/- 4 nM, is obtained by introducing a
      phenethyl moiety on the amino group of D-Cys. In comparison, the most active
      inhibitor in the series of 2-substituted 3-mercaptopropanoic acid is found to be
      20, in which the phenyl ring is linked to the mercaptocarboxylic acid at the
      alpha-position with a methylene unit. A proposal that accounts for the different
      structural requirement for the maximum activity between the two series of
      inhibitors is provided.

PMID- 11831906
TI  - Synthesis and biological activity of the prodrug of class I major
      histocompatibility peptide GILGFVFTL activated by beta-glucuronidase.
AB  - The first synthesis of a prodrug of HLA-A2.1 associated antigenic influenza
      peptide 2a was accomplished. Two methods for synthesis of prodrugs of antigenic
      peptides activated by beta-glucuronidase and comprising a self-immolative 3
      nitrobenzyloxycarbonyl moiety were investigated. Reaction of beta-glucuronic acid
      glycoside of 4-hydroxy-3-nitrobenzyl alcohol (3) with N,N'-disuccinimidyl
      carbonate (DSC) followed by conjugation with AlaOMe, Gly, Thr, Phe-Leu, and Leu
      Arg gave carbamates 4a-4f. Deacetylation of 4b and 4e with MeONa/MeOH gave beta
      glucuronides 5b and 5e. Compound 5e was converted to beta-glucuronic acid
      conjugate 6e by the action of pig liver esterase (PLE). Compound 6e is a
      substrate for beta-glucuronidase. Method of a direct introduction of the prodrug
      residue into antigenic nonapeptide GILGFVFTL (2b) failed. Alternately, glycine
      conjugate 5b was activated to pentafluorophenyl ester 10. Model coupling of 10
      with Phe-Leu gave tripeptide conjugate ester 11a which was hydrolyzed by PLE to
      uronic acid 12. Condensation of 10 with octapeptide ILGFVFTL (9) gave prodrug
      precursor 11b. Octapeptide 9 was prepared by de novo synthesis using a
      racemization-free fragment coupling method. Ester hydrolysis with Ba(OH)(2)/MeOH
      gave the target prodrug 2a which is a substrate for beta-glucuronidase. Prodrug
      2a does not bind to HLA-A2.1 of T2 human cells defective in major
      histocompatibility complex I (MHC I)-associated peptide processing. Addition of
      beta-glucuronidase restored the binding to the level observed with parent
      nonapeptide 2b although higher concentrations of prodrug 2a and enzyme were
      necessary.

PMID- 11831904
TI  - New type of metalloproteinase inhibitor: design and synthesis of new
      phosphonamide-based hydroxamic acids.
AB  - A series of phosphonamide-based hydroxamate derivatives were synthesized, and the
      inhibitory activities were evaluated against various metalloproteinases in order
      to clarify its selectivity profile. Among the four diastereomeric isomers
      resulting from the chirality at the C-3 and P atoms, the compound with a (R,R)
      configuration both at the C-3 position and the phosphorus atom was found to be
      potently active, while the other diastereomeric isomers were almost inactive. A
      number of (R,R)-compounds synthesized here exhibited broad spectrum activities
      with nanomolar K(i) values against MMP-1, -3, -9, and TACE and also showed
      nanomolar IC(50) values against HB-EGF shedding in a cell-based inhibition assay.
      The modeling study using X-ray structure of MMP-3 suggested the possible binding
      mode of the phosphonamide-based inhibitors.

PMID- 11831905
TI  - New strategy for antedrug application: development of metalloproteinase
      inhibitors as antipsoriatic drugs.
AB  - Phosphonamide-based inhibitors were synthesized and evaluated for the inhibitory
      activities against the shedding of epidermal growth factors, amphiregulin and
      heparin-binding EGF-like growth factor, that would participate in the development
      of psoriasis. All compounds exhibited excellent inhibitory activities for these
      EGF sheddings; however, they also inhibited matrix metalloproteinases (MMPs). To
      avoid adverse effects reported by the clinical development of MMP inhibitors, the
      antedrug concept was introduced. Among the phosphonamide inhibitors, the 2,2,2
      trifluoroethyl ester 8d and 2,2-difluoroethyl ester 8c showed rapid decomposition
      in human plasma, which is an essential property for the antedrug. Topical
      applications of these compounds significantly suppressed TPA-induced epidermal
      hyperplasia in murin skin, a model of psoriasis. These results suggested that the
      phosphonamide-based inhibitors have a therapeutic potential for the treatment of
      psoriasis as an antedrug application.

PMID- 11831907
TI  - N-Aryl N'-hydroxyguanidines, a new class of NO-donors after selective oxidation
      by nitric oxide synthases: structure-activity relationship.
AB  - The formation of nitric oxide (NO) was followed during the oxidation of 37 N
      hydroxyguanidines or related derivatives, including 18 new N-aryl N'
      hydroxyguanidines, by recombinant inducible nitric oxide synthase (NOS II).
      Several N-aryl N'-hydroxyguanidines bearing a relatively small, electron-donating
      para subtituent, such as H, F, Cl, CH(3), OH, OCH(3), and NH(2), led to NO
      formation rates between 8 and 41% of that of NO formation from the natural NOS
      substrate, N(omega)-hydroxy-L-arginine (NOHA). The characteristics of these
      reactions were very similar to those previously reported for the oxidation of
      NOHA by NOS:(i) the strict requirement of NOS containing (6R)-5,6,7,8-tetrahydro
      L-biopterin, reduced nicotinamide adenine dinucleotide phosphate, and O(2) for
      the oxidation to occur, (ii) the formation of NO and the corresponding urea in a
      1:1 molar ratio, and (iii) a strong inhibitory effect of the classical NOS
      inhibitors such as N(omega)-nitro-L-arginine and S-ethyl-iso-thiourea. Structure
      activity relationship studies showed that two structural factors are crucial for
      NO formation from compounds containing a C(triple bond)NOH function. The first
      one is the presence of a monosubstituted N-hydroxyguanidine function, since
      disubstituted N-hydroxyguanidines, amidoximes, ketoximes, and aldoximes failed to
      produce NO. The second one is the presence of a N-phenyl ring bearing a
      relatively small, not electron-withdrawing para substituent that could favorably
      interact with a hydrophobic cavity close to the NOS catalytic site. The k(cat)
      value for NOS II-catalyzed oxidation of N-para-fluorophenyl N'-hydroxyguanidine
      was 80% of that found for NOHA, and its k(cat)/K(m) value was only 9-fold lower
      than that of NOHA. Interestingly, the K(m) value found for NOS II-catalyzed
      oxidation of N-(3-thienyl) N'-hydroxyguanidine was 25 microM, almost identical to
      that of NOHA. Recombinant NOS I and NOS III also oxidize several N-aryl N'
      hydroxyguanidines with the formation of NO, with a clearly different substrate
      specificity. The best substrates of the studied series for NOS I and NOS III were
      N-(para-hydroxyphenyl) and N-(meta-aminophenyl) N'-hydroxyguanidine,
      respectively. Among the studied compounds, the para-chlorophenyl and para
      methylphenyl derivatives were selective substrates of NOS II. These results open
      the way toward a new class of selective NO donors after in situ oxidation by each
      NOS family.

PMID- 11831908
TI  - Syntheses, calcium channel agonist-antagonist modulation activities, nitric oxide
      release, and voltage-clamp studies of 2-nitrooxyethyl 1,4-dihydro- 2,6-dimethyl-3
      nitro-4-(2-trifluoromethylphenyl)pyridine-5-carboxylate enantiomers.
AB  - The novel (-)-(S)-2 and (+)-(R)-3 enantiomers of 2-nitrooxyethyl 1,4-dihydro-2,6
      dimethyl-3-nitro-4-(2-trifluoromethylphenyl)pyridine-5-carboxylate were
      synthesized for evaluation as calcium channel modulators. Determination of their
      in vitro calcium-channel-modulating activities using guinea pig left atria (GPLA)
      and ileum longitudinal smooth muscle (GPILSM) showed that the (-)-(S)-2
      enantiomer acted as a dual cardioselective calcium channel agonist (GPLA)/smooth
      muscle selective calcium channel antagonist (GPILSM). In contrast, the (+)-(R)-3
      enantiomer exhibited calcium channel antagonist activity on both GPLA and GPILSM.
      The 2-nitrooxyethyl racemate is a nitric oxide (.NO) donor that released 2.7%
      .NO, relative to the reference drug glyceryl trinitrate (5.3% .NO release/ONO(2)
      moiety), in the presence of N-acetylcysteamine. Whole-cell voltage-clamp studies
      using isolated guinea pig ventricular myocytes indicated that both enantiomers
      inhibit calcium current but that the (-)-(S)-2 enantiomer is a weaker antagonist
      than the (+)-(R)-3 enantiomer. These results indicate that replacement of the
      methyl ester substituent of (-)-(S)-methyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(2
      trifluoromethylphenyl)pyridine-5-carboxylate [(-)-(S)-1] by the 2-nitrooxyethyl
      ester .NO donor substituent present in (-)-(S)-2 provides a useful drug design
      concept to abolish the contraindicated calcium channel agonist effect of (-)-(S)
      1 on vascular smooth muscle. The novel (-)-(S)-2 enantiomer is a useful lead
      compound for drug discovery targeted toward the treatment of congestive heart
      failure, and it provides a useful probe to study the structure-function
      relationships of calcium channels.

PMID- 11831909
TI  - Novel antagonists acting at the P2Y(1) purinergic receptor: synthesis and
      conformational analysis using potentiometric and nuclear magnetic resonance
      titration techniques.
AB  - The human P2Y(1) receptor is widely distributed in many tissues and has a
      classical structure of a G protein-coupled receptor. Activated by adenosine-5'
      diphosphate (ADP), this receptor is essential for platelet aggregation. In the
      present paper, we describe the synthesis of novel P2Y(1) antagonists that could
      be of interest at least as tools to define the physiological roles of the P2Y(1)
      receptor, at best as new antithrombotic agents. Thus, we prepared the 2,N(6)
      dimethyl-2'-deoxyadenosine-3',5'-bisphosphate derivative, 1e. The biological
      activity was demonstrated by the ability of compound 1e to inhibit ADP-induced
      platelet aggregation, shape change, and intracellular calcium rise. This compound
      was a full antagonist at the P2Y(1) receptor with a pA(2) value of 7.11 +/- 0.11
      and was found to be 4-fold more potent than the reference N(6)-methyl-2'
      deoxyadenosine-3',5'-bisphosphate (1a, pA(2) = 6.55 +/- 0.05), revealing the
      potency-enhancing effects of the 2-methyl group. The better activity of 1e as
      compared to 1a was analyzed using both potentiometric and nuclear magnetic
      resonance titration techniques, which highlighted specific conformational
      features of this compound. These results clearly indicate the preference for both
      compounds for an anti conformation at the N-glycosyl linkage. Furthermore, the
      percentage of S conformer of 1e is close to that of 1a, which is nearly 70% at pH
      = 2.8 and increases dramatically when pH increases. From the macroprotonation
      constants, it can be noted that compound 1e is significantly more basic than 1a.
      This is indeed expected for the N1 adenine nitrogen due to the electron-donating
      character of the methyl moiety. By considering the microconstants of the
      phosphate groups, the higher basicity of P3 and P5 for 1e may be due to the
      decrease in the local dielectric constant induced by the substitution of the
      hydrogen atom by a more lipophilic methyl group. Thus, it may be suggested that
      the gain in activity of 1e when compared to the reference compound 1a would
      result from its gain in basicity rather than steric and conformational
      modifications. The synthesis of the first selective radioligand acting at the
      P2Y(1) receptor ([(33)P]-N(6)-methyl-2'-deoxyadenosine-3',5'-bisphosphate, 17) is
      also reported and will be used in the future for efficient screening needed for
      drug optimization.

PMID- 11831910
TI  - Computational studies on tetrahydropyrimidine-2-one HIV-1 protease inhibitors:
      improving three-dimensional quantitative structure-activity relationship
      comparative molecular field analysis models by inclusion of calculated inhibitor-
      and receptor-based properties.
AB  - A computational chemistry study has been performed on a series of
      tetrahydropyrimidine-2-ones (THPs) as HIV-1 protease (HIV-1 PR) inhibitors. The
      present investigation focuses on the correlation of inhibitor-enzyme complexation
      energies (E(compl)), inhibitor solvation energies E(solv)[I], and both polar and
      nonpolar buried surface areas (BSAs) with the observed values of the binding
      affinity (pK(I)). Various combinations of these specific inhibitor- and receptor
      based properties were also evaluated as additional descriptors to three
      dimensional quantitative structure-activity relationship (3D-QSAR) models
      constructed using comparative molecular field analysis (CoMFA). Linear regression
      of the observed pK(I) values with E(compl), E(solv)[I], and the BSAs yielded a
      strong correlation in terms of both self-consistency (r(2) approximately equal to
      0.90) and internal predictive ability (r(cv)(2) > 0.50). The 3D-QSAR models
      obtained from CoMFA using standard partial least-squares (PLS) analysis also
      yielded a strong correlation between the CoMFA fields and the experimental pK(i)
      (r(2) = 0.96; r(cv)(2) = 0.58). Various "enhanced" 3D-QSAR models were
      constructed in which different combinations of the E(compl), E(solv)[I], and BSAs
      were added as additional descriptors to the default steric-electrostatic CoMFA
      fields. Inclusion of E(solv)[I] in particular yielded significant improvement in
      the predictive ability (r(cv)(2) approximately equal to 0.80) of the resultant 3D
      QSAR model.

PMID- 11831911
TI  - Cyclohexylmethylpiperidinyltriphenylpropioamide: a selective muscarinic M(3)
      antagonist discriminating against the other receptor subtypes.
AB  - To discover a highly selective M(3) antagonist, a combinatorial library was
      prepared. The library was designed to identify a novel structural class of M(3)
      antagonists by exploring the spatial arrangement of the pharmacophores in known
      M(3) antagonists. After the evaluation of 1000 library members, a potent M(3)
      antagonist, 14a (K(i) = 0.31 nM), with novel structural features was identified.
      Compound 14a showed high selectivity for M(3) receptors over the other muscarinic
      receptor subtypes (M(1)/M(3) = 380-fold, M(2)/M(3) = 98-fold, M(4)/M(3) = 45
      fold, M(5)/M(3) = 120-fold).

PMID- 11831912
TI  - Selective antagonists at group I metabotropic glutamate receptors: synthesis and
      molecular pharmacology of 4-aryl-3-isoxazolol amino acids.
AB  - Homologation of (S)-glutamic acid (Glu, 1) and Glu analogues has previously
      provided ligands with activity at metabotropic Glu receptors (mGluRs). The
      homologue of ibotenic acid (7), 2-amino-3-(3-hydroxy-5-isoxazolyl)propionic acid
      (HIBO, 8), and the 4-phenyl derivative of 8, compound 9a, are both antagonists at
      group I mGluRs. Here we report the synthesis and molecular pharmacology of HIBO
      analogues 9b-h containing different 4-aryl substituents. All of these compounds
      possess antagonist activity at group I mGluRs but are inactive at group II and
      III mGluRs.

PMID- 11831913
TI  - Photodynamic therapy to control fibrosis in human glaucomatous eyes after
      trabeculectomy: a clinical pilot study.
AB  - OBJECTIVE: To evaluate the safety, tolerability, and clinical effect on
      intraocular pressure (IOP) of a carboxyfluorescein ester as an adjunctive
      antifibrotic therapy in human glaucomatous eyes to control postoperative wound
      healing after trabeculectomy. METHODS: In 10 human glaucomatous eyes with high
      IOPs that underwent 1 to 3 previous surgical procedures for glaucoma, 2'7'-bis-(2
      carboxyethyl)-5-(and-6)-carboxyfluorescein, acetoxymethyl ester was applied 15
      minutes prior to trabeculectomy via a subconjunctival injection followed by
      intraoperative illumination with diffuse blue light (450-490 nm; approximately
      51.9 x 10(3) candelas/m(2)) for 8 minutes. Antifibrotic efficacy was established
      by clinical response, postoperative IOP reduction, slitlamp examination, and
      filtering bleb site photographs. Success was defined as an IOP less than 21 mm Hg
      from baseline without the eye receiving any antiglaucomatous medication or an
      application of antimetabolites. RESULTS: The mean (SD) IOP on the day before
      surgery was 37.2 (11.2) mm Hg. The IOP was 16.6 (3.8) mm Hg in 8 successful eyes
      after a mean (SD) follow-up of 400.1 (38.1) days (P<.001). Two eyes showed
      scarring at the site of the filtering bleb within 1 month. In 1 eye with
      pseudoexfoliation glaucoma IOP decreased to 17 mm Hg but needed topical
      antiglaucomatous medication. Clinical examination revealed none of the following:
      blebitis, uveitis, endophthalmitis, or toxic damage of the adjacent tissues.
      CONCLUSIONS: We report our findings about the first 10 consecutive human
      glaucomatous eyes treated with a single dose of 80 microg of 2'7'-bis-(2
      carboxyethyl)-5-(and-6)-carboxyfluorescein, acetoxymethyl ester during
      trabeculectomy. In contrast to chemotherapeutic agents, cellular photoablation
      acts only on cells having incorporated 2'7'-bis-(2-carboxyethyl)-5-(and-6)
      carboxyfluorescein, acetoxymethyl ester and having been exposed to light of an
      appropriate wavelength. Though safety and efficacy demand a controlled randomized
      study, our method seems to be an effective therapeutic approach to control
      postoperative fibrosis in human glaucomatous eyes with a poor surgical prognosis.
      Multiple factors such as dose of light, means of application, wavelength,
      irradiation area, total dose of the dye, and multiple dosing may be altered in
      the future to improve the antifibrotic effect of photodynamic therapy during
      surgery for glaucoma.

PMID- 11831914
TI  - Identifying live nematodes in diffuse unilateral subacute neuroretinitis by using
      the scanning laser ophthalmoscope.
AB  - OBJECTIVE: To describe use of the scanning laser ophthalmoscope (SLO) to identify
      live nematodes in patients with diffuse unilateral subacute neuroretinitis.
      METHODS: Infrared, red, and blue illumination (780, 633, and 488 nm,
      respectively) in an SLO were used to image and evaluate functional retinal status
      in patients with late-stage diffuse unilateral subacute neuroretinitis. An
      examination to identify live nematodes was performed in the affected eyes.
      RESULTS: Using blue illumination, the ocular fundus appeared dark and provided a
      high-contrast background for the white image of the worm. The red laser was used
      to perform red-on-red perimetry. We also used perimetry stimulus to stimulate the
      worm's movement and pinpoint its location. We precisely defined the relation
      between the fixation point and the worm to plan accurate laser treatment. The
      infrared laser is safe and comfortable for prolonged examination. Using the SLO,
      several physicians simultaneously visualized the ocular fundus. Video output from
      the SLO provided temporal information, excellent for enhancing detection of
      worms, which was displayed dynamically on video. CONCLUSIONS: Although
      examination with a fundus contact lens by skilled ophthalmologists is the method
      of choice, the SLO provides a new examination modality with distinct advantages
      for identifying live worms in young patients with diffuse unilateral subacute
      neuroretinitis.

PMID- 11831915
TI  - Trypan blue staining of epiretinal membranes in proliferative vitreoretinopathy.
AB  - OBJECTIVE: To determine whether trypan blue staining facilitates epiretinal
      membrane (ERM) removal in proliferative vitreoretinopathy. METHODS: In 10
      patients undergoing vitrectomy for proliferative vitreoretinopathy, ERM peeling
      was performed without staining the tissue, until no additional ERMs were clearly
      visible. Then, after a fluid-air exchange, 0.06% trypan blue solution was applied
      onto the retinal surface. After 1 minute, all excess dye was removed and, after
      an air-fluid exchange, ERM peeling was completed. Excised ERM specimens were
      analyzed by transmission electron microscopy. MAIN OUTCOME MEASURES: For each
      patient, the efficacy of trypan blue staining of ERMs during surgery was scored.
      RESULTS: In all patients, intraoperative staining of ERMs with trypan blue was
      found to be a useful adjunct, since the dye consistently improved direct
      visualization and delineation of ERMs and facilitated ERM removal. A clear
      contrast was created between the stained ERMs and the nonstaining, underlying
      retina. Electron microscopy showed that only ERM tissue was removed. No adverse
      reactions related to the use of the dye were observed up to 3 months after
      surgery. CONCLUSIONS: Trypan blue may be an important new tool in the surgical
      management of proliferative vitreoretinopathy, since it may allow a more complete
      and safer ERM removal.

PMID- 11831916
TI  - Gyrate atrophy of the choroid and retina: further experience with long-term
      reduction of ornithine levels in children.
AB  - OBJECTIVE: To determine whether the long-term reduction of plasma ornithine
      levels by way of an arginine-restricted diet in patients with gyrate atrophy will
      slow the progression of this chorioretinal degeneration. DESIGN: Natural history
      study of 2 pairs of siblings with gyrate atrophy treated with an arginine
      restricted diet. MAIN OUTCOME MEASURES: Fundus photography and electrophysical
      and psychophysical retinal function tests. RESULTS: After 16 to 17 years of
      receiving an arginine-restricted diet, the younger sibling in each pair, who was
      prescribed the diet at an earlier age than the older sibling, demonstrated a
      slower progression of lesions compared with the older sibling. CONCLUSIONS: If
      started at an early age, long-term substantial reduction of plasma ornithine
      levels may appreciably slow the progression of the chorioretinal lesions and, to
      a lesser extent, the progressive loss of retinal function in patients with gyrate
      atrophy.

PMID- 11831917
TI  - Short-wavelength sensitivity deficits in patients with migraine.
AB  - OBJECTIVE: To examine short-wavelength sensitivity in patients with migraine
      using short-wavelength automated perimetry (SWAP) and Stiles 2-color increment
      threshold procedures. METHODS: Twenty-five subjects with migraine with (n = 11)
      and without (n = 14) aura and 20 age-matched headache-free subjects underwent
      testing. All subjects underwent standard automated perimetry (SAP) and SWAP
      (using a Humphrey field analyzer; 24-2 presentation pattern). In 2 migraine
      patients (one with and another without aura), the 2-color increment threshold
      procedure was used to determine whether sensitivity losses were specific to short
      wavelength sensitivity pathways or a generalized loss to multiple pathways.
      RESULTS: No statistically significant differences between migraine patients and
      controls were found for mean deviation (MD) or pattern-standard deviation (PSD)
      for SAP. However, for SWAP, MD and PSD were worse for the migraine group (P
      =.04). Twelve migraine patients had more than 4 locations with sensitivity worse
      than the 5% probability level (reference value). Increment threshold
      determinations in the 2 selected migraine patients indicated a selectively
      greater loss for short-wavelength sensitivity mechanisms. CONCLUSIONS:
      Approximately 50% of subjects with migraine (with or without aura) demonstrate
      SWAP sensitivity losses, at times between migraine events. These findings, in
      conjunction with previous results for SAP and flicker perimetry, suggest that
      migraine patients should be excluded from normative databases of visual function,
      and warrant further investigations of the relationship between migraine and
      glaucoma.

PMID- 11831918
TI  - Effects of enzymatic sterilization detergents on the corneal endothelium.
AB  - OBJECTIVE: To evaluate the potential of enzymatic detergents to cause endothelial
      damage and anterior segment inflammation. METHODS: Paired rabbit corneas were
      mounted in an in vitro specular microscope. Endothelia were perfused either with
      the sterile irrigating solution BSS Plus (Alcon Laboratories Inc, Ft Worth, Tex)
      (control) or 0.1%, 0.4%, or 1.0% Medline Enzymatic Detergent (Medline Industries
      Inc, Mundelein, Ill) in BSS Plus. Swelling rates were determined by regression
      analysis. Human endothelia were perfused using 1.56% detergent. All corneas were
      fixed for scanning electron microscopy (SEM) and transmission electron microscopy
      (TEM). Endothelial permeability was determined following perfusion of 0.78%
      detergent. Finally, in vivo intracameral injections with 1.56% or 3.9% detergent
      were performed to evaluate clinical changes and to correlate with histopathologic
      analysis. RESULTS: Dose-related corneal swelling rates were observed. Digital
      specular micrographs revealed greater endothelial cell damage when perfused with
      1.0% detergent. The TEM of endothelia exposed to 1.0% solutions demonstrated
      abnormal vacuolization and dilated extracellular spaces, which manifested as an
      increased corneal permeability to 3 to 4 times that of controls. Human corneas
      swelled comparably to rabbit corneas but demonstrated increased sensitivity when
      evaluated by TEM and SEM. Histopathologic analysis after intracameral injection
      revealed thickened corneas with fewer endothelial cells and irises with increased
      inflammatory and fibrinous responses compared with controls. CONCLUSIONS: Medline
      Enzymatic Detergent causes a dose-dependent corneal swelling, ultrastructural
      damage, increased corneal permeability, and increased inflammatory response in
      the iris after intracameral injection. CLINICAL RELEVANCE: Failure to adequately
      rinse the detergent from surgical instruments may result in corneal edema and
      intraocular inflammation.

PMID- 11831919
TI  - Spatial and temporal processing of threshold data for detection of progressive
      glaucomatous visual field loss.
AB  - OBJECTIVE: To evaluate the effect of spatial and temporal filtering of threshold
      visual field data on the ability of pointwise linear regression (PLR) to detect
      progressive glaucomatous visual field loss. METHODS: Longitudinal visual field
      data (Full-Threshold Program 30-2 test point pattern) were simulated using a
      computer model of glaucomatous visual field progression. This approach permitted
      construction of a "gold standard" because matching visual field data without
      variability could be generated and analyzed. Four clustered progressive defects
      were produced, consisting of 2, 3, 9, and 18 locations, respectively, each with
      progression rates of -1 and -2.5 dB/y. Pointwise linear regression was used to
      identify progressive test locations (criterion for progression of statistically
      significant slope of < or =-1 dB/y, P<.05). Each visual field series was analyzed
      after the following 3 procedures: (1) no filtering (unprocessed data), (2)
      Gaussian spatial possessing (3 x 3 grid), and (3) temporal processing (2 field
      moving average). The effect of spatial and temporal processing on PLR
      discriminatory power for progression detection was quantified by comparison with
      the gold standard. RESULTS: Spatial processing reduced PLR sensitivity to levels
      below that achieved for analysis of unprocessed data for small progressive
      defects (< or =9 locations) or at the low true progression rate (-1 dB/y). Under
      these conditions, spatial processing caused small PLR specificity improvement.
      Spatial processing only improved PLR sensitivity above unprocessed levels when
      progressive defects were large and changing rapidly (progression rate of -2.5
      dB/y). Temporal processing gave consistent PLR improvement in sensitivity for all
      defect sizes and true progression rates. Pointwise linear regression sensitivity
      gain provided by temporal processing allowed progression to be detected 2 to 3
      visual fields earlier than for analysis of raw data. Specificity dropped slightly
      as a result of temporal processing but remained at 89% or above for all
      conditions studied. CONCLUSIONS: Gaussian spatial processing reduces PLR
      discriminatory power with low true progression rates or small progressive defect
      sizes and, therefore, is of limited use for detection of progressive visual field
      loss. Temporal processing improves the sensitivity of PLR and reduces the number
      of tests required to detect progressive loss with minimal loss of specificity.
      CLINICAL RELEVANCE: Image processing techniques can be applied to threshold
      visual field data to enhance sensitivity or specificity of PLR for the
      determination of progressive change. This investigation demonstrates that
      temporal processing may assist with the detection of significant progressive
      visual field loss with fewer test results than unprocessed data.

PMID- 11831920
TI  - A new technique for repairing descemet membrane detachments using intracameral
      gas injection.
AB  - Descemet membrane detachments are not uncommon following cataract surgery, and
      large and extensive detachments can have an impressive presentation, with severe
      corneal edema and marked reduction in visual acuity. Traditional treatment
      regimens have included observation (with the hopes of spontaneous resolution),
      anterior chamber injections of air or viscoelastic, transcorneal suturing, and
      even corneal transplantation for persistent cases. During the past few years,
      intracameral injection with either sulfur hexafluoride (SF6) or perfluoropropane
      (C3F8) gas has gained increasing acceptance as an efficient and effective
      treatment option for Descemet membrane detachments. Previously described
      techniques of gas injection have required corneal and paracentesis incisions;
      sterile blades, cannulas, and other instruments; and occasionally, an operating
      room setting. We describe a simple, safe, and effective technique for
      intracameral gas injection that can be performed by one person at the slitlamp
      microscope or in a minor operating room with minimal equipment.

PMID- 11831921
TI  - The drawstring temporary tarsorrhaphy technique.
AB  - Tarsorrhaphy is used for the treatment of severe ocular surface disorders and
      cases of ocular exposure. Temporary tarsorrhaphy has been shown to aid in the
      healing of corneal epithelial defects. A variety of temporary techniques have
      been suggested that allow closure for epithelial healing but also allow access to
      the eye. The drawstring temporary tarsorrhaphy uses rubber bolsters and 6-0
      prolene sutures passed through the eyelid margin. This modification of the
      temporary tarsorrhaphy allows for complete closure of the eyelids while providing
      easy opening and closing. In addition, this technique is easy to perform in
      almost any setting.

PMID- 11831922
TI  - "Who's on first?": Considering the options for primary glaucoma therapy.

PMID- 11831923
TI  - The ophthalmoscope in the lifetime of Hermann von Helmholtz.

PMID- 11831924
TI  - Conjunctival papillomas caused by human papillomavirus type 33.

PMID- 11831925
TI  - Bilateral iridociliary T-cell lymphoma.

PMID- 11831926
TI  - Pigmented medulloepithelioma of the ciliary body.

PMID- 11831928
TI  - Neuroblastoma within a congenital orbital teratoma.

PMID- 11831927
TI  - Endogenous Nocardia asteroides endophthalmitis.

PMID- 11831929
TI  - Substance P, insulinlike growth factor 1, and surface healing.

PMID- 11831930
TI  - A novel KRIT1/CCM1 truncating mutation in a patient with cerebral and retinal
      cavernous angiomas.

PMID- 11831931
TI  - Retinal alterations in acquired partial lipodystrophy: a case report.

PMID- 11831932
TI  - Exercise-induced vasospastic amaurosis fugax.

PMID- 11831933
TI  - Photo essay: disastrous complications following a bilateral, same-day laser in
      situ keratomileusis (LASIK) procedure.

PMID- 11831934
TI  - Photo essay: complications of Miragel: pseudotumor.

PMID- 11831935
TI  - Retinal detachment and culture-proven bacterial endophthalmitis in the EVS.

PMID- 11831937
TI  - Diabetes and the EVS: a different interpretation of the results.

PMID- 11831939
TI  - The post-endophthalmitis vitrectomy study era.

PMID- 11831940
TI  - Republication of color figures.

PMID- 11831941
TI  - [Clinical experience of long-distance electronic fetal heart rate monitoring
      system by telephone].
AB  - OBJECTIVE: To explore the value of the long-distance electronic fetal heart rate
      monitoring system by telephone and explore a new way of self-monitoring at home
      for pregnant woman. METHOD: 204 high risk pregnant women came to our clinic were
      enrolled in this study. Complications included pregnancy induced hypertension
      (PIH), intrauterine growth retardation (IUGR), anemia, diabetes, hemolysis,
      nephropathy. In the study group, 97 women took the terminal part of the fetal
      heart rate monitoring system home and were requested to auscultate and count
      fetal heart rate three times a day, while another 107 cases did the self
      monitoring by fetal movement counting daily and served as control group. For the
      study group, whenever woman felt any abnormality of her baby, she could contact
      the long-distance electronic fetal heart rate (FHR) monitoring center in hospital
      by telephone immediately. The signal of fetal heart beat and fetal movement was
      converted and analyzed in the electronic FHR monitoring center by computer at the
      same time. The fetal heart rate curve was printed out, and diagnosis and
      management could be made. Age, gestational weeks, high risk factors, abnormal non
      stress test (NST), Apgar score and birth weight of newborn were analyzed between
      the experimental and control group retrospectively. RESULTS: There were no
      obviously differences in age, gestational weeks, weight of newborn, high risk
      factors between the 2 groups. The incidence of abnormal NST and Apgar score of
      newborn were significantly higher in the study group than that in the control
      group, while the incidence of neonatal asphyxia was significantly lower.
      CONCLUSIONS: This study suggested that the long-distance electronic FHR
      monitoring by telephone was a reliable, sensitive and applicable method of self
      monitoring for pregnant woman at home, use of this system could decrease the
      incidence of fetal distress, brain damage and perinatal mortality, thus improves
      the quality of perinatal care.

PMID- 11831942
TI  - [Clinical use of central electronic monitoring system].
AB  - OBJECTIVE: To evaluate the effects of central electronic monitoring system
      (CEMS). METHODS: A total of 1,216 patients with > or = 37 weeks of gestation
      assigned as monitoring group, were performed central electronic monitoring during
      labor from Nov. 1997 to Mar. 1998. A total of 1,137 patients with same
      gestational age assigned as control group, were monitored by using intermittent
      auscultation during labor from Nov. 1996 to Mar. 1997. The rate of fetal
      distress, neonatal asphyxia, cesarean section, and using of forceps or vacuum
      extractor in the 2 groups were compared. RESULTS: Patients in the monitoring
      group had a higher fetal distress rate (12.8%) than that of the control group
      (9.8%, P < 0.05), but a significantly lower neonatal asphyxia rate (2.3%) than
      that of the control group (4.8%, P < 0.01). There were no significant differences
      in the overall cesarean rate, cesarean rate for fetal distress, overall use rate
      of forceps or vacuum extractor delivery, and vaginal operative delivery rate for
      suspected fetal distress between the two groups (P > 0.05). CONCLUSION: Quality
      for obstetric care was significantly improved by application of central
      electronic monitoring for labor management, it didn't increase the cesarean
      section rate and vaginal operative delivery rate, but decreased the neonatal
      asphyxia rate.

PMID- 11831943
TI  - [Significance of amnioinfusion and amniotic fluid exchange under continuous
      internal fetal heart rate monitoring for management of fetal distress during
      labor].
AB  - OBJECTIVE: To discuss the significance of amnioinfusion and amniotic fluid
      exchange under continuous internal fetal heart rate (FHR) monitoring for
      management of fetal distress during labor. METHODS: 136 cases with frequent
      variable deceleration (VD) and meconium stained amniotic fluid during labor were
      divided into two groups: the study group (68 cases) and the control group (68
      cases). The former were treated by amnioinfusion and amniotic fluid exchange,
      while oxygen inhalation, change of body position, and intravenous infusion for
      the control group. RESULTS: In the study group, VD disappeared or relieved in 62
      cases obviously, and the efficacy rate reached 91.2% (62/68). 48 cases with II
      degree meconium stained amniotic fluid were treated by amniotic fluid exchange,
      amniotic fluid became clear or turned to I degree stained in 39 cases. In the
      control group, VD relieved in 20 cases, the efficacy rate was 19.4%,
      significantly lower than that of the study group (P < 0.01). In the study group,
      cesarean section rate was 14.7% neonatal asphyxia 7.4% while they were 47.1% and
      48.5% in the control group respectively (P < 0.01; P < 0.01). Neonatal pneumonia
      caused by meconium aspiration occurred in 13 cases, meconium aspiration syndrome
      (MAS) 8 cases, with 5 newborns died in the control group, while there was no
      neonatal death in the study group. There was no significant difference on
      puerperal morbidity between the 2 groups (P > 0.05). CONCLUSIONS: Amnioinfusion
      and AF exchange during labor are one of the effective treatment methods for fetal
      distress and prevention for MAS.

PMID- 11831944
TI  - [Clinical value of fetal monitoring in intrahepatic cholestasis of pregnancy].
AB  - OBJECTIVE: To study the clinical value of fetal monitoring in intrahepatic
      cholestasis of pregnancy (ICP). METHODS: Two hundred and six cases of ICP,
      delivering in our hospital from Dec. 1993 to Sept. 1998 were investigated. In
      these cases, 206 cases were examined by the fetal monitoring and vibratory
      acoustic stimulation test (VAS-T), 157 cases by ultrasonic umbilical artery flow
      analysis, and 127 cases by fetal electrocardiograph (FECG). RESULTS: There is a
      significant difference between normal and abnormal groups of the poor perinatal
      prognosis in contraction stress test (CST) and oxytocin challenge test (OCT) and
      ultrasonic umbilical artery flow analysis (P < 0.005, P < 0.05). There is no
      difference between normal and abnormal groups of the poor perinatal prognosis in
      NST, VAS-T and FECG. CONCLUSION: CST, OCT and ultrasonic umbilical artery flow
      analysis have the higher clinical value to detect the poor placental function and
      to foretell the perinatal prognosis in ICP.

PMID- 11831945
TI  - [Correlation of intrauterine growth retardation with endocrine parameters].
AB  - OBJECTIVE: To investigate the relationship between intrauterine growth
      retardation (IUGR)and endocrine parameters and to assess the effects of the main
      endocrine factors on IUGR. METHODS: The concentrations of growth hormone (GH),
      insulin, triiodothyronine (T(3)), tetraiodothyronine (T(4)), and thyroid
      stimulating hormone (TSH) were measured in maternal serum, umbilical blood and
      amniotic fluid. The samples were collected from 23 term pregnancies with IUGR,
      and 42 normal pregnancies served as control. Growth hormone and insulin were
      measured by radioimmunoassay, and T(3), T(4) and TSH by microradioimmunoassay.
      RESULTS: The concentrations of GH, insulin and T(4) in umbilical blood were lower
      in IUGR group than that in the normal group (IUGR: GH 4.63 microg/L vs 7.01
      microg/L, insulin 10.68 mIU/L vs 31.44 mIU/L, T(4) 0.68 mg/L vs 1.07 mg/L. P <
      0.05, 0.05, 0.05), the TSH level in umbilical blood was higher in IUGR than that
      in the control group (10.84 mIU/L vs 5.74 mIU/L. P < 0.01). The concentration of
      GH in maternal serum and insulin in amniotic fluid in IUGR group were also lower
      than that in normal group (GH 1.77 microg/L vs 2.74 microg/L, P < 0.01; insulin
      5.84 mIU/L vs 15.64 mIU/L, P < 0.01). CONCLUSIONS: This study confirms previous
      observation that insufficiency of GH might be a pathogenesis of IUGR. The
      decrease of GH and insulin might compromise the basic metabolism of the fetus.
      Besides, the change of early hypothyrosis of fetus with IUGR might benefit them
      to live in unfavorable environment.

PMID- 11831946
TI  - [Correlation between epidermal growth factor receptor messenger RNA expression
      and the onset of labor].
AB  - OBJECTIVE: To study the correlation between epidermal growth factor receptor
      messenger RNA expression and the onset of labor. METHOD: Semiquantitative reverse
      transcriptase polymerase chain reaction, using GAPDH as internal standard, was
      applied to determine the levels of epidermal growth factor receptor messenger RNA
      in human myometrium (n = 20) and fetal membranes (n = 20) before and during
      labor. RESULTS: In myometrium, epidermal growth factor receptor messenger RNA
      increased from 0.91 +/- 0.32 before labor to 1.33 +/- 0.23 after the onset of
      labor (P < 0.05). In fetal membranes, epidermal growth factor receptor messenger
      RNA increased from 1.05 +/- 0.30 before labor to 1.65 +/- 0.71 after the onset of
      labor (P < 0.05). CONCLUSION: The study indicates it is Up-regulation of
      epidermal growth factor receptors messenger RNA expression in myometrium and
      fetal membrane before and after the onset of labor.

PMID- 11831947
TI  - [Study on perinatal group B Streptococcus carriers and the maternal and neonatal
      outcome].
AB  - OBJECTIVE: To investigate the group B streptococcus (GBS) colonization rate and
      the relationship between vaginal colonization of GBS and the maternal and
      neonatal outcome. METHODS: 3% TH selective broth media were used for culture of
      GBS. The vaginal samples were collected during different pregnant periods (before
      20 weeks' gestation; 20-28 weeks; after 34 weeks' gestation) and other samples
      from different sites after labor (including neonatal throat, ear, umbilicus and
      placenta, umbilical blood, maternal blood, etc). RESULTS: The GBS carrier rate in
      1 039 pregnant women was 11.07% (115/1,039). The colonization rate of different
      treating times was 29.73% (test three times), 15.50% (test twice) and 9.86% (test
      one time) respectively. The carrier rate of three-time-test was significantly
      higher than that of two times test (P < 0.01) and that of only one time (P <
      0.01). The carrier rate in three periods was 16.84% (< 20 weeks), 18.40% (20-28
      weeks) and 14.90% (> 34 weeks) respectively. Obstetric complications associated
      with GBS carrier were similar with those of non-carrier. Neonatal carrier rate
      was 9.95%. The neonatal carrier rate in the group of carrier mothers was higher
      than that of non-carrier mothers (14.29%:7.26%). The rate of neonatal pneumonia
      and the upper respiratory tract infection in GBS-carrier-mother was higher than
      that of non-carrier mothers (11.01%:9.71%; 8.27%: 6.07%) while it was similar in
      neonatal carrier group and non-carrier group (20.00%:14.92%; 10.00%:4.97%).
      CONCLUSION: GBS might be one of vaginal pathogens in Chinese women, but it is not
      severe enough to threaten the health of pregnant women and their newborns.

PMID- 11831948
TI  - [Changes of endometrial macrophages and nature kill cells during luteal phase and
      early pregnancy].
AB  - OBJECTIVE: To investigate the effect of endometrial microenvironment on
      pregnancy. METHODS: The number of macrophage and nature kill (NK) cells in
      decidua and endometrium were determined in 19 cases of early pregnancy and 11 non
      pregnant women respectively by cytometric analysis. RESULTS: The percentages of
      macrophages (leukocyte antigen molecules CD14 positive) and NK cells (CD56
      positive) were significantly increased in decidua of first trimester as compared
      with those in luteal endometrium (P < 0.01). The number of CD(56)(+)CD(16)(-)
      subset of NK cells increased significantly during early pregnancy. While the
      number of CD(56)(+)CD(16)(+) subset did not change. CONCLUSION: The endometrial
      macrophages and NK cells may be involved in the mechanism of the fetal protective
      immune reaction during pregnancy.

PMID- 11831949
TI  - [Effects of serum and decidual tissue fluid in early pregnant women on natural
      killer cells activity and lymphocyte proliferation].
AB  - OBJECTIVE: To study the effects of serum and decidual tissue fluid in early
      pregnant women on natural killer cells (NK cells) activity and lymphocyte
      proliferation. METHOD: The effects of the serum and decidual tissue fluid
      obtained from 32 normal early pregnant women on NK cells activity and lymphocyte
      proliferation were tested by isotope incorporation methods. Sera of 25
      nonpregnant women were chosen as controls. RESULTS: The NK cells activity and
      lymphocyte proliferation of sera and decidual tissue fluids from early pregnant
      women were lower than those of sera from nonpregnant women (P < 0.01). So were
      those of decidual tissue fluid as compared with sera during early pregnancy (P <
      0.005). CONCLUSIONS: Serum and decidual tissue fluid from early pregnant women
      expressed immunosuppressive effects. It is possible that these effects of
      decidual tissue fluid play an important role in regulating local immune status of
      pregnant uterus.

PMID- 11831950
TI  - [Measurement of macrophage colony-stimulating factor during in-vitro
      fertilization and embryo transfer cycles].
AB  - OBJECTIVE: To explore the influences of macrophage colony-stimulating factor (M
      CSF) on follicle development, ovulation, fertilization and embryo quality during
      in-vitro fertilization and embryo transfer (IVF-ET) cycles. METHODS: 36 patients
      underwent 54 cycles of controlled ovarian hyperstimulation by gonadotropin
      releasing hormone agonist-human menopausal goudotropin-human chorionic
      gonadotropin for IVF-ET program. M-CSF concentrations in serum were measured at
      early follicular phase, mid-follicular phase and the day of oocyte retrieval by
      enzyme-linked immunosorbent assay. Follicular fluid (FF) on the day of egg
      retrieval was also measured for M-CSF concentration. RESULTS: M-CSF concentration
      in serum gradually increased throughout ovarian hyperstimulation and reached a
      peak on the day of oocyte retrieval. M-CSF concentration in FF was significantly
      higher than that in serum on the same day (P < 0.01). The M-CSF concentration in
      FF from follicles where oocytes could be retrieved, fertilized or with a diameter
      > or 16 mm, volume > or 2 ml, was significantly higher than those from follicles
      where oocyte could not be retrieved, fertilized or with a diameter < 16 mm,
      volume < 2 ml, respectively (P < 0.01). However, there was no significant
      difference in M-CSF concentration of FF between high and low embryo grade groups
      (P > 0.05). CONCLUSIONS: M-CSF may play an important role as an intraovarian
      regulator in the process of follicle development, maturation and ovulation.
      Therefore, M-CSF may exert an effect on fertilization process but not on the
      embryo quality.

PMID- 11831951
TI  - [Investigation of prognostic factor and treatment mode for undifferentiated
      cervical carcinoma].
AB  - OBJECTIVE: To analyse the prognostic factor and investigate the treatment mode
      for undifferentiated cervical carcinoma. METHODS: The recurrent rate, the
      metastatic rate and the survival rate were analysed retrospectively for 146
      patients with stage I-II cervical carcinoma of poor differentiation treated with
      radical operation, operation/chemotherapy, operation/radiotherapy,
      operation/chemotherapy/radiotherapy from Jan. 1990 to Oct. 1998. RESULTS: The
      recurrent rate of patients treated with radical operation/chemotherapy (18.18%)
      or radical operation/radiotherapy (24.32%) was lower than that of patients only
      treated with radical operation (36.36%) or operation/chemotherapy/radiotherapy
      (42.11%) for the cases of stage II or deep muscle invasion (P < 0.05). The
      recurrent rate of patients treated with radical operation/radiotherapy (22.22%)
      was lower than that of patients only treated with radical operation (2/2) for the
      cases with local lymphaden positive (P < 0.05). The investigation also showed
      that the distant metastatic rate of patients treated with radical
      operation/chemotherapy was 0.00%, which was lower than that of patients treated
      with radical operation 5.56% (P < 0.05). The 3-year survival rate was 100.00% and
      88.53% respectively for the cases only treated with radical
      operation/chemotherapy or operation/radiotherapy; and it was lower for the cases
      treated with radical operation 76.74% (P < 0.05). CONCLUSIONS: The prognosis of
      undifferentiated cervical carcinoma is related to the lymph node metastasis, the
      International Federation of Gynecology and Obstetrics stage and the treatment
      methods. The local recurrent rate and distant metastasis might be reduced by 2
      courses of chemotherapy or radiotherapy post-operatively. The recurrent rate
      could not be reduced effectively by the combination therapy of
      operation/chemotherapy/radiotherapy.

PMID- 11831952
TI  - [Management of micrognathia deformity associated with obstructive sleep apnea
      syndrome by distraction osteogenesis].
AB  - OBJECTIVE: To review the early results of lengthening of the mandible by
      distraction osteogenesis for the correction of micrognathia deformity and
      treatment of the obstructive sleep apnea syndrome (OSAS) simultaneously. METHODS:
      5 cases with micrognathia deformity associated with OSAS resulted from
      unilateral/bilateral temporomandibular joint ankylosis had undergone mandibular
      distraction osteogenesis. In all of the patients intraoral device was employed.
      Cephalometric radiographs and polysomnograms were obtained preoperatively and
      postoperatively. RESULTS: The average distraction distance was 15.28 mm (range
      8.5 mm to 24.4 mm). The micrognathia deformity was corrected effectively, at the
      mean time the incapacious pharyngeal airway was ameliorated. The patients' Apnea
      Index (AI) had been decreasing, SaO(2) during sleep had got to rise. CONCLUSIONS:
      Compared with the traditional surgery for the micrognathia associated with OSAS,
      the technique of mandibular distraction osteogenesis has the advantages of
      avoiding bone grafting and donor side morbidity, expanding the surrounding soft
      tissue concurrently, reducing the extent of operation and stability of the
      treatment effects.

PMID- 11831953
TI  - [The treatment of tongue squamous cell with N0].
AB  - OBJECTIVE: To evaluate the validity of selective surgery for the N(0) neck in
      squamous cell carcinoma of the mobile tongue. METHODS: 116 patients with N(0)
      neck of the mobile tongue cancer who underwent comprehensive RND and 5 patients
      who had a selective RND were reviewed retrospectively. RESULTS: According to the
      suggestion of division of neck level, 7 patients had metastasis at level I; 21,
      level II; 10, level III, 1 case for level IV or V each. There were 5 cases with
      level III involvement as a first echelon of metastasis which was peculiar for the
      neck metastasis of mobile tongue. CONCLUSIONS: For N(0) neck of the mobile tongue
      cancer, a neck dissection of level I-III or level I-IV is more than enough.

PMID- 11831954
TI  - [Changes of elastase in gingival crevicular fluid after periodontal treatment of
      adult periodontitis patients].
AB  - OBJECTIVE: To examine the changes of elastase in the supernatant (EA-s) and in
      the pellet (EA-p) after centrifuge in gingival crevicular fluid (GCF) before and
      after periodontal treatment. METHODS: GCF was sampled with filter paper strips by
      intra-pocket method to determine EA levels. Forty-three teeth of eight subjects
      were included. EA-s and EA-p were determined separately using the subtract Meosuc
      ala-ala-val-pro-NA. RESULTS: EA-s per site and per ml, EA-p per site and the
      ratio of EA-s/EA-p (S/P) decreased significantly after non-surgical periodontal
      treatment (P < 0.001), while EA-p concentration didn't change (P > 0.05).
      CONCLUSIONS: GCF-EA-s and EA-p could act as objective parameters to evaluate the
      effect of periodontal therapy, especially EA-s and S/P, which may be sensitive
      diagnostic parameters for determining periodontal disease activity.

PMID- 11831956
TI  - [The study of risk ratio on genetic factors in recurrent aphthous ulcer].
AB  - OBJECTIVE: To study the relation of SCE, MNR, CAR of lymphocytes in RAU patients
      and RAU. METHODS: SCE, MNR, CAR of 60 RAU patients were determined, and were
      analyzed by non-condition Logistic regression and the risk ratio of the 3
      studying factors was calculated. RESULTS: SCE, MNR and CAR were important risk
      factors among many complicated causes of RAU. CONCLUSION: The results of the
      study showed essentially that RAU patients could have some pathological genetic
      predisposition and abnormal genetic materials congenitally.

PMID- 11831955
TI  - [The effects of the complex of rhBMP2 and fibrin sealant on dental pulp].
AB  - OBJECTIVE: To investigate the reparative dentine formation induced by the complex
      of recombinant human bone morphogenetic protein 2 (rhBMP2) and fibrin sealant
      (FS) in dog tooth. METHODS: Freshly exposed molars, premolars and cuspids were
      treated with the complex of rhBMP2/FS, rhBMP2 and Ca(OH)(2) paste which served as
      control. RESULTS: The wound healing of exposed pulp treated with FS seemed to be
      better than that without FS. Dentine bridge formation was observed in pulp
      treated with the complex at 7 days, with rhBMP2, Ca(OH)(2) at 28 days. At 63 days
      after operation, the cases of tubular dentine bridge formation of the pulp
      treated with the complex were more than that of pulp treated with rhBMP2.
      CONCLUSION: The synergistic effects of FS and the complex rhBMP2 exist and can be
      used as bioactive pulp capping agent.

PMID- 11831957
TI  - [An assessment of fluoride release from a compomer and four resin-modified glass
      ionomers].
AB  - OBJECTIVE: To compare the fluoride release into water from a compomer (Dyract)
      and four resin-modified glass-ionomer cements (Fuji II LC, Photac-Fil, VariGlass,
      Vitremer). METHODS: Five specimens of each material were prepared according to
      manufacturers' instructions and placed into 3.0 mm diameter x 2.7 mm thick
      disposable Teflon molds. The specimens were placed in well-sealed polypropylene
      vials with 2 ml of de-ionized water and stored in an incubator at 37 degrees C.
      The solutions were replaced weekly and the levels of fluoride (ppm) were analysed
      at day 1, 7, 30 and subsequently every 28 days for 253 days. The results were
      analysed using one-way ANOVA followed by the Student-Newman-Keuls range test.
      RESULTS: All materials except the compomer (Dyract) showed high initial release
      values of fluoride which decreased exponentially, then showed a slow decline
      during the ensuing time. Initial fluoride release values were significantly
      different between Dyract, VariGlass, and the three other resin-modified glass
      ionomers. The compomer released significantly less fluoride than did the other
      resin-modified glass-ionomers. CONCLUSION: With high caries risk patients, it may
      be most beneficial to use a high fluoride release resin-modified glass-ionomer
      cement as the restorative material of choice.

PMID- 11831958
TI  - [Expression of transforming growth factor-beta 1 mRNA and osteopontin mRNA in UMR
      106 cells under mechanical stimulation].
AB  - OBJECTIVE: To investigate the effects of the mechanical stretching on the
      expression of osteopontin (OPN) mRNA and transforming growth factor-beta 1 (TGF
      beta 1) mRNA in a rat osteosarcoma cell line (UMR-106), and to unveil the
      cellular mechanism of mechanical force-induced bone remodeling. METHODS: An
      apparatus was designed and fabricated by which force was loaded onto the cultured
      cells in vitro. Digoxin-labeled cDNA probes were used for in situ hybridization
      in combination with image analysis technique to relatively quantify the
      intensities of the hybridization signals. RESULTS: Various magnitudes and
      durations of the mechanical stretching did exert different influences on the
      intensities of the mRNAs' expression. Of all the combinations, the low
      tension/frequency group showed the most remarkable alteration of TGF-beta 1, as
      increased from 0.0899 to 0.1756 (P < 0.01). Some putative relations lay between
      the expressions of the OPN mRNA and the TGF-beta 1 mRNA. CONCLUSION: The
      mechanical stretching can inevitably influence the expression of OPN mRNA and TGF
      beta 1 mRNA. The beneficial alteration obtained in using low tension/frequency
      action mode suggests and verifies the use of relatively constant and light force
      to move teeth in clinical orthodontics.

PMID- 11831959
TI  - [Histogenesis and development of membranous basal cell adenoma of the salivary
      gland].
AB  - OBJECTIVE: To investigate the histogenesis and development of membranous basal
      cell adenoma in the salivary glands. METHODS: A histological and
      immunohistochemical study was carried out on 12 cases of membranous basal cell
      adenoma in the salivary glands. RESULTS: In 4 cases, multiple focal
      proliferations of striated ducts in the surrounding salivary gland were
      conspicuous, which allowed tracing the development of the tumors from their
      origin. The earliest changes were characterized by hyperplasia of the basal cells
      of striated ducts. Continuous ductal proliferation lead to the formation of
      microadenomas. CONCLUSIONS: Proliferation of basal cells of the striated ducts
      apparently participate in, and play a main role in the histogenesis of some
      membranous basal cell adenomas of the salivary glands.

PMID- 11831960
TI  - [The effects of suicide gene therapy system on adenoid cystic carcinoma of
      salivary gland in athymic mice].
AB  - OBJECTIVE: To study the effects of HSV-tk/GCV system on adenoid cystic carcinoma
      (ACC) in vivo. METHODS: The cell strain of ACC-M (highly metastatic to the lung)
      was inoculated into the flank of nude mice, then treated with HSV-tk/GCV system.
      RESULTS: The system can inhibit the tumor growth greatly, moreover this function
      has bystander effect. CONCLUSION: HSV-tk/GCV system can be to treat ACC.

PMID- 11831961
TI  - [A comparison of polymerase chain reaction with other two widely used methods in
      detection of Porphyromonas gingivalis].
AB  - OBJECTIVE: To compare the efficiency of polymerase chain reaction (PCR) with
      cultural method and indirect immunofluorescence (IF) in detection of
      Porphyromonas gingivalis (P.g) in oral plaque samples. METHODS: 92 subgingival
      plaque samples were collected from patients of three kinds of periodontal
      disease. A program using PCR to detect Fimbrilin gene (Fim A) was designed to
      detect P.g. The efficiency of this PCR method was compared with cultural method
      and IF. RESULTS: The positive-rate of PCR was 94.6%, while that of cultural
      method and IF was only 48.9% and 68.5% respectively. The difference was
      significant in statistical analysis (P < 0.001). CONCLUSION: PCR is more
      sensitive than culture method and IF in detecting pathogens of periodontal
      diseases. The study provides a simplified and efficient method for oral clinical
      use.

PMID- 11831962
TI  - [Distribution of calcitonin gene-related peptide-like immunoreactive fibres in
      the temporomandibular joint of rat].
AB  - OBJECTIVE: To observe the distribution of calcitonin gene-related peptide-like
      immunoreactive (CGRP-LI) nerve fibres in rat's temporomandibular joint (TMJ).
      METHODS: The avidin-biotin-peroxidase complex method and image analysis were
      employed to detect CGRP-LI nerve fibres in frozen sections of TMJs in eight rats.
      RESULTS: CGRP-LI nerve fibres were plentifully distributed in TMJs except the
      central disc band and bone, mainly in the periphery of blood vessels, especially
      arteries. Density: anterior disc attachment and capsule, (454.6 +/- 72.8) mm(2);
      posterior portion, (302.7 +/- 43.4) mm(2); lateral portion, (240.2 +/- 23.6)
      mm(2); medial portion, (229.6 +/- 25.0)mm(2); and peripheral portion of disc,
      (202.4 +/- 35.2) mm(2). CONCLUSION: CGRP-LI nerve fibres were widely distributed
      in rat TMJ and were a part of trigeminal sensory nerve. Density was highest in
      anterior disc attachment and capsule.

PMID- 11831963
TI  - [Effects of autogenous periodontal ligament cell transplantation on periodontal
      tissue regeneration in dogs].
AB  - OBJECTIVE: To evaluate the effect of autogenous periodontal ligament cell (PDL)
      transplantation in periodontal tissue regeneration. METHODS: PDL cells derived
      from the same dog were cultured with alpha-MEM. 1 x 10(5) cells of first passage
      were allowed to attach to the collagen membrane for 24 hours. The membrane-cells
      were transplanted into periodontal defect in the same dog. Then the defects were
      covered with e-PTFE membranes. The defects covered only with e-PTFE were the
      controls. Eighteen teeth of 6 dogs for each group were included. The dogs were
      sacrificed after 6 weeks. RESULTS: The results showed that new bone formation
      (4.00 +/- 0.13) mm in test group was significantly higher than that of in control
      group (3.09 +/- 0.28) mm, P < 0.05. The new cementum formation in test group was
      better than control group (P < 0.05). CONCLUSION: The results suggested that PDL
      cell transplantation with guided tissue regeneration technique could enhance
      periodontal tissue regeneration in dogs.

PMID- 11831964
TI  - [Effect caused by uptake of different levels of calcium to enamel fluorosis in
      rats].
AB  - OBJECTIVE: To study the effects caused by uptake of different levels of calcium
      to dental fluorosis in rats. METHODS: Weanling rats were raised on water
      containing 0.1 mol/L fluoride and food containing low, normal and high levels of
      calcium for 2 months. The concentration of fluoride in enamel was analysed by F
      ion-selective electrode. The microradiographic examination and light-density
      analysis were performed. The enamel structure was examined under SEM. RESULTS:
      The more calcium was ingested, the lower level of fluoride amount in enamel was
      observed (P < 0.01). With increasing food calcium ingestion, the light density
      value was decreasing, and the level of enamel mineralization was increasing (P <
      0.01). CONCLUSIONS: With increasing food calcium ingestion during the development
      of teeth, the level of dental fluorosis is decreasing. The calcium supply is
      effective in protection from fluoride toxicity to a certain extent.

PMID- 11831965
TI  - [An electron microscopic histochemical study on the fibrous formation in
      pleomorphic adenoma of the salivary gland].
AB  - OBJECTIVE: To study the kinds of fibers and mechanism of fibrous formation in
      myxochondroid tissue of pleomorphic adenoma. METHODS: Eight cases of pleomorphic
      adenomas of salivary gland were studied by histological and electron microscopic
      histochemical techniques. RESULTS: The histological study showed that collagenous
      fibers and elastic fibers which constituted the trestle were distributed in
      myxochondroid areas of pleomorphic adenoma. The electron microscopic
      histochemical study showed that the myxochondroid tissue contained slender
      collagen fibrils measuring 50 nm in diameter and heavily stained elastic fibers.
      In cytoplasm of the myxochondroid cells two types of the Golgi-derived vesicles
      were seen: one was small round vesicles with a uniform electron dense core of
      amorphous material and heavily stained; another type was small round vesicles
      with a non-uniform electron dense core of filamentous material and stained grey.
      These materials were released into the extracellular space by cytoplasmic
      exocytosis. CONCLUSIONS: Neoplastic myoepithelial cells have the ability to
      synthesize and secrete procollagen and precursor of elastin, thus forming
      collagenous fibers and elastic fibers in myxochondroid areas.

PMID- 11831966
TI  - [A clinical evaluation of two new materials for restoration of dental wedge
      shaped defects].
AB  - OBJECTIVE: To evaluate clinically two new materials (Dyract Cem and 3M-Vitremer)
      for restoration of dental wedge-shaped defects with modified USPHS evaluation
      criterion. METHODS: 317 teeth with wedge-shaped defects were restored by Dyract
      Cem and 192 teeth by 3M-Vitremer clinically. The 1 year and 2 year follow-up
      results were evaluated with modified USPHS evaluation criterion. RESULTS: 1 year
      successful rate was 91.17% in Dyract Cem group and 81.77% in 3M-Vitremer group,
      and 2 years successful rates were 88.64% and 80.21% separately. The differences
      of successful rates between the two groups are significant statistically, but
      there are no significant differences in main indexes except stain rate when
      analysed item by item with USPHS evaluation criterion. Successful rates were
      related with the abrasive degree of the restored teeth. CONCLUSIONS: Both Dyract
      Cem and 3M-Vitremer have high successful rates and a lot of advantages for
      restoration of dental wedge-shaped defects. The modified USPHS evaluation
      criterion is a valuable method for clinical evaluation.

PMID- 11831967
TI  - [Effects of estrogen on experimental tooth movement in osteoporosis rats].
AB  - OBJECTIVE: To investigate the effects of estrogen on the orthodontic tooth
      movement and alveolar bone in osteoporosis rats. METHODS: Thirty 3 month-old
      female sprague-dawley rats were divided randomly into three groups (control,
      osteoporosis and estrogen). In the three groups, the distances of tooth movement
      and the number of osteoclast were measured and compared. Histologic changes were
      observed. RESULTS: Compared with the control group, in first month, the distances
      of orthodontic tooth movement was increased by 43.3% in osteoporosis group and by
      30.7% in estrogen group; the number of osteoclast was increased by 64.4% and by
      32.9% respectively. In second month, the distances were increased by 68.5% in
      osteoporosis group and by 24.9% in estrogen group; the number of osteoclast was
      increased by 68.7% and by 15.0% respectively. In addition, estrogen promoted the
      alveolar bone-forming and inhibited the bone resorption. CONCLUSION: It is
      suggested that the estrogen may affect the rate of orthodontic tooth movement on
      postmenopausal osteoporosis patient.

PMID- 11831968
TI  - [The establishment of the model for differential diagnosis of borderline cases
      with anterior crossbite using fuzzy set theory].
AB  - OBJECTIVE: To introduce the fuzzy set theory to orthodontics by using the
      diagnostic information drawn out from the diagnosed cases to solve the problem of
      borderline- case diagnosis. METHOD: Lateral cephalometric radiographs of 107
      anterior crossbite patients in early permanent dentition were traced, measured,
      and 31 variables calculated. Diagnosis was made by experienced specialists and
      the cases were divided into three groups: dental anterior crossbite (52 cases),
      borderline cases (22 cases) and skeletal anterior crossbite (33 cases). Among 85
      cases with accurate diagnosis we selected 70 cases to establish 6-factor model
      using stepwise discriminant analysis. This afforded 100 percent correct
      respective check and the predictive diagnosis of the other 15 cases showed that
      its correction rate was 93.3 percent which proved that most useful information
      was included. Then the contributions of the six variables were calculated and we
      established two sets: skeletal anterior crossbite set and dental anterior
      crossbite set with skeletal and dental means to be their thresholds. For each
      case the individual measurements of the six variables were standardized and
      afterwards transferred into constituent ratio and at the same time their degrees
      of membership of these two sets were calculated according to the distance between
      its location and the two thresholds. Using this fuzzy model we got the individual
      scores of the two sets. The diagnosis of the patient was coincident with the set
      of higher scores. This model was testified by 85 cases with accurate diagnosis
      and its correction was absolute. RESULT: 22 borderline cases were diagnosed by
      this model. CONCLUSION: The two-set difference were far less than that of the
      cases with accurate diagnosis which prove the model was reasonable.

PMID- 11831969
TI  - [Management of the temporalis flap donor site].
AB  - OBJECTIVE: To describe a technique of using a sterilized form of moldable cold
      cured acrylic, Cranioplastic, for camouflaging the depressed temporalis flap
      donor site, and to assess the long term morbidity and aesthetic results. METHODS:
      A retrospective clinical assessment of 50 consecutive patients who had temporalis
      myofascial flap surgery from 1988 to 1995. Any complications of healing,
      neurosensory deficit were recorded. The aesthetics of the temporal region was
      graded by subjective and objective methods. The histology of the tissues around
      the implant in one patient was examined under light microscopy. RESULTS: There
      was no major complications noted except immediate postoperative seroma formation
      and temporary paresis of the temporal branch of facial nerve. A satisfactory
      restoration of aesthetics at the temporal donor site was achieved with the
      moldable acrylic technique in 96% of patients. The capsular tissues surrounding
      the implanted acrylic consisted of hyalinized collagen fibres with scanty
      inflammatory cells. CONCLUSIONS: The use of moldable acrylic to restore the
      temporalis donor site is a simple, versatile and effective technique with minimal
      long term morbidity. The aesthetic result of the camouflage was satisfactory and
      the material exhibits good biocompability.

PMID- 11831970
TI  - [Compensation of external jugular vein to the reflux of cerebral blood after
      bilateral ligation of the internal jugular vein].
AB  - OBJECTIVE: To investigate the effects of conserving external jugular veins for
      compensating the back flow of intracranial veins. METHODS: The rhesus monkey was
      underwent bilateral radical neck dissection to simulate that performed in the
      human. In operation, the changes of intracranial pressure (ICP) after ligating
      these jugular veins was observed. RESULTS: The results indicate that ligation of
      the external and internal jugular veins will increase the ICP obviously, but
      conserving external jugular veins will reduce the increase of ICP and shorten the
      recovery time from increased ICP. CONCLUSIONS: The conservation of the external
      jugular veins will compensate the back flow of intracranial veins after RND. The
      experiment provides a simple and effective method for the prevention of
      intracranial complications and preservation of the flow of facial veins.

PMID- 11831971
TI  - [The influence of different root length on stress distribution in the bone around
      abutment root of telescopic overdenture].
AB  - OBJECTIVE: To investigate the influence of bone height around the roots on stress
      distribution in a mandible with two canines remained and covered with an
      telescopic overdenture. METHODS: Three-dimensional finite element method.
      RESULTS: As the height of the bone around the roots decreased, the stress
      increased. But the maximum stress in the bone in this study is lower than that in
      the bone around the canine under normal condition. CONCLUSION: In the mandible,
      when the alveolar bone resorption reaches the apical 1/3 of canine (root length
      4, 5 mm), if part of the tooth crown was removed, to make an acceptable
      crown/root ratio, so the canine can be used as the abutment of an overdenture.

PMID- 11831972
TI  - [The role of matrix vesicles during development of the mineralizing tissues of
      tooth germ and craniofacial bone].
AB  - OBJECTIVE: To evaluate the role of matrix vesicles (MVs) during the development
      of mineralizing tissues. METHODS: The ultrastructure of MVs of tooth germ,
      calvarial bone and mandibular bone were observed by transmission electron
      microscopy in fetal Wistar rat. RESULTS: (1) The MVs were formed by osteoblast of
      the secret type, dentinoblast and process; (2) There was a mature process of the
      MVs in the extracellular matrix. The appearance of the hydroxyapatite (HAP) was a
      major mature feature; (3) HAP formed initially in the MVs entered into collage
      matrix and eventually mineralized; (4) The shifting sign of HAP from MVs to the
      surface of collage fibril was observed. CONCLUSIONS: The MVs played an important
      role in the biomineralization, but the special arrange pattern of mature collage
      fiber provided a suitable environment and a model to the growth of HAP for
      further mineralization.

PMID- 11831974
TI  - Hepatectomy for huge primary liver cancer: report of 171 patients.
AB  - OBJECTIVE: To discuss the safety and feasibility of hepatectomy for huge primary
      liver cancer (PLC). METHODS: The effect of resection of huge PLC was examined
      retrospectively. Some problems about resection of huge PLC were discussed.
      RESULTS: In 171 patients with huge PLC undergoing hepatectomy, 2 (1.2%) died in
      one month after operation. The 1-, 2-, 3-, 5- and 10-year survival rates of the
      patients were 66.1%, 42.1%, 32.7%, 12.2% and 2.3%, respectively. The effect of
      prolonging survival time was significant. CONCLUSION: Hepatectomy for huge PLC is
      safe, feasible, and effective.

PMID- 11831973
TI  - [The effect of protein kinase C on the invasive behavior of human salivary
      adenoid cystic carcinoma in vitro].
AB  - OBJECTIVE: To explore the relationship between protein kinase C (PKC) and
      invasion/metastasis of salivary adenoid cystic carcinoma and to explore the
      possibility of treatment against invasion/metastasis of the tumor cell by PKC
      inhibitor. METHODS: SACC-83 cell line cells were treated by endogenous PKC
      inhibitor BS-PKCI extracted from bovine spermatozoa and exogenous PKC inhibitor
      H(7), while the adhesion to basement membrane, movement (expressed by the cell
      numbers moving out from agarose drop and the furthest distance) and invasive
      capacity in vitro were observed. RESULTS: (1) The two inhibitors suppressed
      significantly adhesion of the tumor cell to basement membrane (P < 0.05). (2) The
      two inhibitors suppressed significantly movement of the tumor cells (P < 0.05).
      (3) The two inhibitors suppressed significantly invasive capacity of the tumor
      cells in vitro (P < 0.01). CONCLUSIONS: There was a close relationship between
      PKC and invasion/metastasis of salivary adenoid cystic carcinoma; the two PKC
      inhibitor suppressed significantly adhesion, movement and invasive capacity of
      SACC - 83 cell line cells in vitro.

PMID- 11831975
TI  - Pancreatic insulinomas: experience in 220 patients.
AB  - OBJECTIVE: To summarize the experience in the diagnosis and treatment of
      insulinoma. METHODS: We retrospectively reviewed 220 patients with insulinoma
      confirmed surgically in the PUMC Hospital from 1953 to 1999. They were 131 men
      and 89 women, aged on average 39 years. RESULTS: In the 220 patients, the average
      interval from the onset of symptoms to diagnosis was 35 months. 54% of the
      patients were misdiagnosed before admission to the hospital. In 214 patients
      underwent operation, 201 (93.9%) had benign tumor and 12 (5.6%) malignant one.
      The diameter of 78% tumors was less than 2cm. 90.7% tumors were single and 9.3%
      were multiple. 37.1% tumors were located in the head and uncinate process of the
      pancreas, 26.1% in the body, 36.1% in the tail, and 0.7% ectopic. 95.5% patients
      had Whipple's triad and the ratio of insulin to glucose was greater than 0.3 in
      89% patients. The positive rates of B-ultrasound, CT and MRI for localization
      before operation were low, but those of angiography and PTPC were 62.8% and 88%
      respectively. Most patients could be cured by simple enucleation of tumor. The
      main complications were pancreatic fistulae and pancreatitis. CONCLUSION: It is
      important for surgeons to familiarize with insulinoma, the most common islet cell
      tumor, for a better treatment.

PMID- 11831976
TI  - [Combined five tumor markers in detecting primary hepatic carcinoma].
AB  - OBJECTIVE: To increase the detection rate of primary hepatic carcinoma (PHC) and
      to diagnose PHC earlier. METHODS: AFP was combined with r-glutamyle
      transpeptidase (r-GT), alpha-fucosidase (AFU), tumor necrosis factor-alpha (TNF
      alpha) and DR-70. RESULTS: The positive detection rate of PHC negative AFP with
      combined four markers was 9.4%. The total positive detection rate of PHC with
      combined five tumor markers reached 98.0% which was significantly higher than
      that with AFP (P < 0.01). CONCLUSIONS: The positive detection rate of PHC can be
      increased by combined five tumor markers. It is helpful in diagnosing PHC earlier
      and can differentiate PHC from liver cirrhosis.

PMID- 11831977
TI  - [p16 gene deletion and point mutation in highly purified fresh breast neoplasm].
AB  - OBJECTIVE: To study the form and frequency of p16 gene deletion and point
      mutation in human breast neoplasm and the effective detection. METHODS: Cell
      culture was made using repeat-adhering method to purify human breast neoplasm
      cells and PCR-SSCP analysis in 14 highly purified fresh breast neoplasm, 14 fresh
      none-purified specimens, 27 paraffin-embedded specimens and corresponding normal
      tissues beside neoplasms. RESULTS: The rate of p16 gene deletion and point
      mutation was 42.9% (6/14) in the highly purified group, in which exon 1st - 3rd,
      showed homozygous deletion (5 cases) and exon 2nd showed mutation (1 case). The
      rate of p16 gene mutation in the other three groups was 7.1%, 7.4% and 4.9%. The
      detection rate of mutation was significantly higher in the highly purified group
      than in the other three groups (P < 0.01), but it was not significantly different
      in the other three groups (P > 0.05). CONCLUSIONS: p16 gene deletion and point
      mutation exist in primary breast cancer. Homozygous deletion and small fragment
      deletion may be an important mechanism of inactivation in human breast neoplasm.
      Purified cancer cells will enhance the detection rate.

PMID- 11831978
TI  - [Detection of remnants after removal of medullary thyroid carcinoma].
AB  - OBJECTIVE: To assess whether calcium stimulation test or somatostain-receptor (SS
      R) imaging could early detect remnants after removal of medullary thyroid
      carcinoma (MTC). METHODS: Calcitonin stimulation (calcium element 3 mg/kg weight,
      i.v. 10 min), carcino-embryonic antigen (CEA), gastrin (GST) and vasoactive
      intestinal peptide (VIP) were tested in 14 patients with postoperative MTC. SS-R
      imaging was used to localize the remnants after removal of MTC in patients with
      elevated calcitonin. RESULTS: Calcitonin stimulation test showed that the peak
      value of serum calcitonin was elevated in all patients, of whom 7 had the
      elevated vatue of basic calcitonin and peak calcitonin. In the 7 patients, SS-R
      imaging showed normal CEA, GST and VIP. CONCLUSIONS: It is necessary for patients
      after removal of MTC to perform calcitonin stimulation test for detecting
      remnants early. SS-R imaging may be useful for localizing remnants and metastatic
      foci. CEA, GST and VIP are not significant in monitoring MTC after operation.

PMID- 11831979
TI  - [Color duplex ultrasonography, percutaneous transpopliteal venography and
      photoplethysmography assess venous reflux in the lower extremities].
AB  - OBJECTIVES: To assess the scope of photoplethysmography (PPG), color duplex
      ultrasonography, percutaneous transpopliteal venography for evaluating chronic
      venous disease. METHODS: Color duplex ultrasonography, percutaneous
      transpopliteal venography, and PPG and were used in 40 patients their results
      were compared. RESULTS: Color duplex ultrasonography and percutaneous
      transpopliteal venography for evaluating venous reflux was not significant (P >
      0.05) in the femoral-popliteal venous segment. The accuracy of PPG in evaluating
      venous reflux was 67% compared with that of color duplex ultrasonography.
      CONCLUSIONS: PPG as the first test is often used for chronic venous disease.
      Color duplex ultrasonography can provide sufficient information for treatment of
      patients the. Percutaneous transpopliteal venography is necessary when
      noninvasive test can not provide sufficient information.

PMID- 11831980
TI  - [Low-molecular-weight heparin for preventing deep-vein thrombosis after total
      joint arthroplasty].
AB  - OBJECTIVE: To evaluate the efficacy and safety of low-molecular-weight heparin
      (LMWH) in preventing deep-vein thrombosis (DVT) after total hip and knee
      replacement (THR, TKR). METHODS: From November 1997 to March 1999, we performed
      total joint replacement for 47 control patients (34 knees, 28 hips) and for 31
      patients (19 knees, 17 hips) who had been given low-molecular-weight heparin for
      preventing deep-vein thrombosis. All patients received venography of the operated
      limbs after operation. RESULTS: DVT occurred in 19.4% of the LMWH patients (26.3%
      in TKR, 11.8% in THR) and the reduction was significant (P < 0.05) compared to
      the control group (48.4%, 55.9%, 39.3% respectively). The incidence of proximal
      DVT was also reduced significantly (P < 0.05) from 19.4% of the control group to
      2.8% of the LMWH group. CONCLUSION: Low-molecular-weight heparin can
      significantly reduce the incidence of deep-vein thrombosis after total joint
      replacement.

PMID- 11831981
TI  - [Vascular endothelial factor of meningomas and peritumoural vasogenic brain
      edema].
AB  - OBJECTIVE: To study the expression of vascular endothelial growth factor (VEGF)
      in meningomas correlated with peritumoral vasogenic brain edema (PVBE) and
      angiogenesis. METHODS: VEGF protein expression in 33 patients with meningomas (12
      men, average 50 +/- 12 years; 21 women average 46 +/- 14 years) was examined by
      immunohistochemical and western blotting. The number of microvessels which were
      immunostained with von willelrand factor was counted and PVBE was assessed
      blindly before MRI scan or CT scan. RESULTS: The expression of VEGF protein was
      found in 75.8% (25/33). The mean rate of immunostaining was 2.03 and the mean
      rate of PVBE was 2.39. The rate of staining intensity was correlated with PVBE
      rate (r = 0.7352, P < 0.01) and vascular counts (r = 0.6974, P < 0.01). VEGF
      protein isoform of molecular sizes corresponding to VEGF165 was detected in
      cytosolic extracts of meningomas. CONCLUSIONS: VEGF is highly related to PVBE and
      angiogenesis of meningoma. Wide-spread distribution of VEGF in meningomas
      suggests VEGF165 isoform.

PMID- 11831982
TI  - [HLA-amino acid residue matching in organ transplantation].
AB  - OBJECTIVE: To present a new matching policy-HLA amino acid residue matching (Res
      M) for Chinese population. METHODS: Based on the outcome of genotyping for HLA
      alleles in massive samples, we presented new Res M according to 10 groups of
      amino acid residue for class I and, groups of DR/DQ for class II and compared
      them with HLA six-antigen match program (Ag M). The influence of Res M on early
      renal function, acute rejection and 1-5 year graft survivals were retrospectively
      analyzed in 316 cases of first cadaver kidney transplantation. RESULTS: The rate
      of Res-matched transplants increased greatly. The rate of 0 mismatch (MM)
      recipients increased from 0.3% by Ag M to 10% by Res M, and that of 0-1 MM
      transplants from 3.2% to 42.4%. Clinical study showed that 1 - 5 year graft
      survival with 0 - 1 Res-MM was similar to kidneys with 0 - 2 Ag-MM. Compared to 3
      - 4 Res-MM, the early renal function obviously improved (88.8% vs 46.7%), acute
      rejection decreased (14.9% vs 86.9%), 1 - 5 year survival was increased by 10% -
      26% (P < 0.05), and graft survival increased by 14% - 35% (P < 0.01) in
      recipients with 0 - 1 Res-MM. Cox regression showed that in 10 factors affecting
      the graft survival, Res-MM was most significant (risk ratio 21.73). CONCLUSION:
      New Res M has proved to be suitable for clinical application in Chinese
      population, especially for cadaver kidney transplantation.

PMID- 11831983
TI  - [Expression of VEGF and tumor angiogenesis in bladder cancer].
AB  - OBJECTIVE: To evaluate expression of vascular endothelial growth factor (VEGF)
      and its relation to angiogenesis in bladder cancer. METHODS: The expression of
      VEGF by immunohistochemical staining was examined in 68 cases of primary
      transitional carcinoma (TCC) and 7 subjects with normal urothelium. Microvessel
      density (MVD) in 40 cases of invasive bladder cancer was determined by Factor
      VIII immunohistochemical staining. RESULTS: The expression of VEGF was negative
      or low level in all normal bladder tissue but high in bladder cancer. VEGF and
      MVD were closely related to tumor cell nuclear grade and clinical stage. The
      average MVD was higher in the cases with the high level expression of VEGF, than
      in those with the low level expression of VEGF. CONCLUSIONS: This study indicates
      that VEGF is positively correlated with the occurrence and progression of bladder
      cancer. VEGF is one of the primary angiogenic factors for bladder cancer, and is
      able to induce tumor angiogenesis and accelerate tumor growth. Quantification of
      VEGF may provide a valuable marker for a poorer prognosis of patients.

PMID- 11831984
TI  - [Beta-catenin and its mRNA in renal cell carcinoma].
AB  - OBJECTIVES: To investigate the role of beta-catenin in renal cell carcinoma.
      METHODS: The expression of beta-catenin in 26 cases of renal cell carcinoma was
      studied by LSAB immunohistochemistry, Western blotting and RT-PCR. RESULTS: The
      expression of beta-catenin was higher in cancer tissues than in normal kidney
      tissues in 25 cases and the level of beta-catenin was associated with tumor
      stage. The expression was obviously higher in pT3 and pT4 than in pT1 and pT2 (P
      < 0.01). The expression of its mRNA was not higher in tumor cells than in normal
      cells. Beta-catenin was expressed mainly in cytoplasm. CONCLUSIONS: Beta-catenin
      might be related to the occurrence and development of kidney tumor.

PMID- 11831986
TI  - [In vitro model of hyperacute rejections in swine to human xenotransplantation].
AB  - OBJECTIVE: To evaluate the efficiency of inhibiting hyperacute rejections in
      swine to human xenotransplantation through expressing human CD(59) protein on the
      membrane of cultured pig aortic endothelial cells (PAECs) by transgenic methods.
      METHODS: The cultured PAECs and human umbilical vein endothelial cells (HUVECs)
      were identified by fluorescent and immunohistochemical methods. The constructed
      eukaryorotic expression vectors containing the human CD(59) cDNA, LXSN-CD(59)
      were identified by the methods of restriction endonucleases cleavage, agarose gel
      electrophoresis, and polymerase chain reaction. LXSN and LXSN-CD(59) were
      transfected into the PAECs separately with lipofectinmine mediated method. Stable
      transfectants were selected using G418. Cells expressing maximum human CD(59)
      protein were selected by FACS. These clones were incubated with the media
      containing human serum or monkey serum. The LDH released into the media was
      measured to assess the function of the hCD(59) protein. RESULT: Comparing with
      the control cells, we found that the cells expressing the human CD(59) protein
      released less LDH when they were incubated with human serum or monkey serum (P <
      0.01). CONCLUSION: Hyperacute rejections may be inhibited through expressing the
      human complement regulatory protein CD(59) on the membrane of PAECs by transgenic
      methods.

PMID- 11831985
TI  - [Expression of bcl-2 and p16 in transitional cell carcinoma of urinary bladder].
AB  - OBJECTIVE: To study the relationship between the expression of proto-oncogene bcl
      2 and MTS1/p16 in transitional cell carcinoma of bladder and prognosis. METHODS:
      Immunohistochemical SABC method was used to detect the expression of proto
      oncogene bcl-2 and MTS1/p16 in 51 paraffin-embedded primary transitional cell
      carcinoma of bladder specimens and 5 normal bladder mucosa specimens. RESULTS:
      The positive expression of bcl-2 was seen in 80.2% (42/51) tumors. There was
      statistically significant correlation between prognosis and the positive
      expression of bcl-2. The positive expression rate was higher in tumors with
      poorer prognosis than in those with better prognosis (P < 0.05). The expression
      of p16 protein was positive in 50.9% (26 of 51) in tumors and negative in all 5
      normal bladder mucosae. The positive expression rate of p16 descended with
      increasing grade, stage and poorer prognosis. Clinicopathological characteristics
      and prognosis were related to the expression of p16 (P < 0.05). The positive
      expression of bcl-2 versus negative expression of p16 were seen in 20 of 51 of
      tumors, with distributing grade I 3/11, grade II 9/26, grade III 8/14, Tis - T(1)
      6/28, T(2) 10/17, T(3) 4/6, A group 5/20, B group 4/16, and C group 11/15,
      respectively. Both bcl-2 and p16 were positively expressed in 22 of 51 of tumors.
      Their positive expressions were higher in tumors with lower grade, stage and
      better prognosis than in those with worse clinicopathological characteristics and
      poorer prognosis (P < 0.05). CONCLUSIONS: Over-expression of bcl-2 appears to be
      common in bladder cancer; over-expression of proto-oncogene bcl-2 and
      inactivation of the MTS1/p16 gene are likely to be contributing factors for
      primary bladder cancer; and they can be the prognostic indicators for
      transitional cell carcinoma of urinary bladder.

PMID- 11831987
TI  - [Effects of recombinant human growth hormone on cortical bone of ovariectomized
      rats].
AB  - OBJECTIVE: To study the effects of recombinant human growth hormone on cortical
      bone of middle femur and vertebra of variectomized rats. METHODS: Forty 6 month
      old SD rats received low or high dose of growth hormone subcutaneously 3 months
      after ovariectomy for 8 weeks. Bone density and biomechanical strength of the
      femur were measured, and the thickness of cortical bone of the middle femur and
      L(2) vertebra was observed. The results were compared with those in estrogen
      group. RESULTS: Growth hormone increased the thickness of cortical bone and
      biomechanical strength and bone density. Estrogen therapy showed no effects on
      bone density and biomechanical strength of cortical bone. CONCLUSION: Recombinant
      human growth hormone can prevent bone loss from cortical bone of ovariectomized
      rat.

PMID- 11831988
TI  - [In vitro culture of human osteoblasts].
AB  - OBJECTIVE: To modify the digestion and culture of human osteoblasts for releasing
      a large amount of cells. METHODS: Bone tissue was harvested and digested by
      trypsin for several times to remove blood cells and fibroblasts. After cultured
      for a couple of days in incubator, bone chips were digested again by trypsin for
      several times, and a large amount of pure osteoblasts were released and used for
      researches. The remaining chips were digested by trypsin repeatedly until enough
      cells were harvested. Black nodes were seen in confluent cell layer. Osteoblasts
      were confirmed by their unique secretion of a large amount of alkaline
      phosphatase (AKP), osteocalcin (OCN) and type I collagen. RESULTS: Under
      fluorescent microscope, black node was "golden yellow" in color, a characteristic
      of bone node. Secretion of AKP (2.76 +/- 0.56) IU/ml and OCN (1.875 +/- 0.549)
      ng/ml of osteoblasts was higher than those of fibroblasts. There was only type I
      collagen in supernatant without type III. CONCLUSION: The modified osteoblast
      digestion and culture can release a large amount of pure osteoblasts in a short
      period with no fibroblastic adulteration.

PMID- 11831989
TI  - [Long-term therapeutic effects of extended radical resection and radical
      resection of cancer of cardia and stomach fundus].
AB  - OBJECTIVE: To study the best range of radical resection in the treatment of
      cancer of the cardia and fundus of stomach. METHODS: 418 patients with cancer of
      the cardia and fundus of stomach underwent radical resection. Of them 192 were
      treated by extended radical resection (extended group), and 226 by radical
      resection (radical group). The 5-year and 10-year survival rates were followed up
      and compared in the two groups. RESULTS: Analysis failed to demonstrate
      significant difference between the two operations for TNM stage I and II (P >
      0.05). For stage III, however, the 5-year and 10-year survival rates in the
      extended group increased by 14.2% and 15.9% as compared with those in the radical
      group (P < 0.05). The two groups survival rates were similar for stage IV (P >
      0.05). CONCLUSIONS: To completely clean the lymph nodes of splenic hilus and
      artery and improve long-term survival rate, extended radical resection including
      spleen and body and tail of the pancreas should be recommended for stage III
      patients with cancer of the cardia and fundus of stomach when their serosa was
      involved or lymph node metastasis took place.

PMID- 11831990
TI  - [Modified total cavopulmonary connection for treating patients with functional
      single ventricle].
AB  - OBJECTIVE: To modify the classic procedure for better surgical results of total
      cavopulmonary connection (TCPC). METHODS: Modified TCPC was performed in 13
      patients with functional single ventricle. In the modified TCPC procedure, the
      distal end of the superior vena cava (SVC) was connected with the upper edge of
      the right pulmonary artery (RPA) with the anastomosis orifice near the left side,
      and the proximal end with the lower edge of RPA with the anastomosis orifice near
      the right side. Among them, intra-atrial tunnel was established with a partial
      tube of PTFE using the lateral tunnel technique in 8 patients, and the distal end
      of the inferior vena cava (IVC) was directly connected with the lower edge of RPA
      using extracardiac conduit in the beating heart in 5. RESULTS: One patient (7.7%)
      died early. Twelve patients survived and had the SatO(2) (94.6 +/- 1.2)%
      postoperatively while inspiring air. Angiography showed that most blood from IVC
      enters the right lung and most blood from SVC the left lung. No late mortality
      was seen during the follow up for 6 months to 2 years and 2 months. NYHA class I
      was noted in 10 patients and class II in 2. Echocardiography showed that left
      ventricular volume reduced significantly and ventricular function was normal.
      CONCLUSIONS: Modified TCPC produces optimal blood flow between the two lungs,
      elevates postoperative Sat O(2) effectively, decreases ventricular volume load
      and improves ventricular functions.

PMID- 11831992
TI  - [Partial sympathectomy for treating palmar hyperhidrosis with VATS].
AB  - OBJECTIVE: To review the experience with partial sympathectomy for treating
      palmar hyperhidrosis with VATS. METHODS: Between July 1995 and June 1999, 50
      patients with palmar hyperhidrosis (26 males and 24 females, mean age 26.7 years)
      were operated. The major symptom was excessive sweating of hands, feet, and
      axcillaries, sometimes in drops. Thoracoscopy was performed under general
      anesthesia with a standard single-lumen endotracheal intubation with the patient
      in a semi-sitting position and arms stretched at 90 degrees. The approach through
      two small ports on the chest wall was done using VATS. As the lung was depressed
      by CO(2) insufflation in a low pressure, an excellent view of the upper
      mediastinum was obtained. Ganglia T(2) through T(4), sometimes T(5) were resected
      with a electrocautery probe. Bilateral procedures were completed in the same
      position. RESULTS: All patients after operation became dry immediately after
      sympathetic denervation with a few minor complications. Occasional side effect
      was moderate compensatory sweating of the trunk. One case had recurrence but
      sweating was much less than before operation. CONCLUSIONS: Because of excellent
      view of the upper mediastinum for sympathetic denervation of the hand and
      axcillaryies, the effect of partial sympathectomy for palmar hyperhidrosis is
      satisfactory and permanent.

PMID- 11831991
TI  - [Separation of thoracopagus conjoined twins].
AB  - OBJECTIVE: To sam up the experience in diagnosis and separation of a thoracopagus
      conjoined twins. METHODS: Thoracopagus twin boys were admitted for evaluating
      possible separation and repair at age of 21 days. X-rays, CT, MRI, and ultrasound
      scan of torso showed separate and normal gastrointestinal and biliary tracts,
      little shared vasculature, but shared pericardium, diaphragm and liver
      parenchyma. The chest junctions were at the sternums and the most inferior two
      pairs of the ribs. One twin (twin A) had a protruding heart with VSD and ASD.
      RESULTS: The infants were separated successfully at age of 45 days. The chest
      defect of twin A was closed with aid of a polyester pericardial patch graft and a
      silicon supporter. Managing anesthesia met some difficulty in understanding of
      the anatomical and physiological consequences of the complex anomaly. They are
      had brain edema and multiple system organ failures after separation, and were
      cured under intensive care. They are alive and well 6 months after surgery.
      CONCLUSIONS: Careful preoperative evaluation proper anesthesia and surgical
      technique, and postoperative care are essential to the successful separation of
      the conjoined twins.

PMID- 11831993
TI  - [Posttransplantation diabetes mellitus].
AB  - OBJECTIVE: To study the clinical rules of posttransplantation diabetes mellitus
      (PTDM). METHODS: 21 patients treated from Dec. 1992 to Sept. 1998 were analysed.
      RESULTS: The morbidity of PTDM was 16.3% of total patients in the corresponding
      period. Between the groups of PTDM and NON-PTDM, there was statistical
      significance in age, kidney function and family diabetic history. It was not
      related to CSA bottom concentration and acute rejection. In this group 2 cases
      were complicated by hyperosmolar nonketotic diabetic comas (9.5%) and 11 various
      infections (52.4%). CONCLUSIONS: PTDM as a secondary diabetes due to
      antirejection drugs and allograft kidney function may cause serious consequences
      if it is treated improperly.

PMID- 11831994
TI  - Surgical treatment of portal hypertension: 45 year experience.
AB  - OBJECTIVE: To review the experience in surgery for 912 patients with portal
      hypertension. METHODS: The 912 patients were divided into three groups: before
      1978 (group A), 1978 - 1989 (group B), and 1990 - 1998 (group C). The results
      were reviewed of portosystemic shunt (PSS), disconnection and disconnection plus
      PSS for emergency and elective operation at different periods. RESULTS: In the
      912 patients of groups A, B, C, the number of PSS, disconnection, and PSS plus
      disconnection was 345, 13, 0; 84, 209, 0; 63, 204, 63, respectively. The number
      of emergency operation was 45, 13 and 4 in each group. The operative mortality of
      shunt in the groups A, B, C was 7.82%, 7.14% and 0, respectively; that of
      disconnection in the groups A, B, C 15.38%, 6.28% and 4.94%; and that of PSS plus
      disconnection in group C 3.51%. Encephalopathy occurred in 14.37% of the PSS
      group, in 5.68% of the disconnection group, and in 5.77% of the disconnection
      plus PSS group. Rebleeding occurred in 10.78% of the PSS group, in 18.95% of the
      disconnection group, and in 7.69% of the disconnection plus PSS group.
      CONCLUSIONS: Operative indications for the cirrhotic patients with portal
      hypertension depend on their liver function. For those patients with poor liver
      function, surgery is considered when their liver function is improved. We suggest
      prophylactic operation is valuable. Other indices from barium meal, color
      ultrasound, and endoscopy are also considered. The number of emergency operation
      has been decreasing. Since the 1980s, disconnection operation has been adopted
      increasingly. In our hospital, the number of patients receiving disconnection has
      been increasing from the early 1980s and the operation has almost replaced shunt
      operation in the 1990s. Disconnection combined with splenorenal shunt can lower
      the portal pressure and maintain the portal flow. Disconnection combined with
      splenorenal shunt seems to be a better procedure of choice.

PMID- 11831995
TI  - [Coronary venous variation in patients with portal hypertension].
AB  - OBJECTIVES: To observe the changes in the anatomic variation and the hepatofugal
      flow of coronary vein and to evaluate the clinical significance of these changes
      in patients with portal hypertension. METHODS: The anatomic variations and the
      retrograde flow of the coronary vein, and the portal antegrade flow and the
      portal pressure were observed by direct and indirect portography, direct
      measurement of portal pressure and Doppler sonography in 200 cirrhotic patients
      with portal hypertension. RESULTS: Single branch and two branches of the coronary
      vein were noted in 79.46% and 20.54% of the patients with portal hypertension
      respectively by direct portography. The sites of coronary vein arising from the
      portal vein, splenic vein or portosplenic junction were found in 62.33%, 27.35%
      or 8.07% respectively. The confluence of coronary vein and portal vein was found
      in most patients with variceal bleeding and recurrent bleeding after
      devascularization. The confluence of the coronary vein and splenic vein was
      observed in most patients with refractory ascites without variceal bleeding.
      Arterial portography demonstrated retrograde opacification of the coronary vein
      in 26.19% (grade II portal venous pattern), 56.64% (grade III portal venous
      pattern), 100% (portal thrombosis and action bleeding) 47.79% (controuing periods
      of bleeding), and 19.05% (refractory ascites). CONCLUSIONS: The anatomic
      variation of the coronary vein may be related to variceal bleeding in cirrhotic
      patients with portal hypertension and the retrograde opacification of the
      coronary vein is a significant sign of variceal bleeding.

PMID- 11831996
TI  - [Magnetic resonance angiography in assessing changes of pre-and post
      disconnective portal system in patients with portal hypertension].
AB  - OBJECTIVE: To evaluate the role of magnetic resonance angiography (MRA) in
      assessing the portal system changes in patients with portal hypertension after
      pericardial devascularization and splenectomy. METHODS: The portal diameter,
      blood velocity and flow, collateral circulation, variceal vein and other portal
      parameters of 15 patients with portal hypertension receiving pericardial
      devascularization and splenectomy and splenectomy were comparatively evaluated
      with Siemens 1.5 T MRI 1 week before operation and 2 weeks after operation.
      RESULTS: The portal diameters decreased after operation, with the disappearance
      or alleviation of esophageal and fundal variceal veins. In 15 patients, 9 showed.
      The blood velocity and flow of the portal veins were lower postoperatively. than
      those preoperatively; In 15 patients, 9 showed increased gastric imaging
      intensity after operation. CONCLUSIONS: MRA can provide high quality and concrete
      3-dimensional information about the portal system and hemodynamics of portal
      hypertensive patients. It is an important non-invasive way in evaluating the
      effects of operations and long-term follow-up. Postoperative gastric venous
      congestion possibly causes increased portal hypertensive gastropathy after
      disconnection.

PMID- 11831998
TI  - [Comparison of TIPS, a modified Sugiura procedure and TIPS plus a modified
      Sugiura procedure for portal hypertension].
AB  - OBJECTIVE: Transjugular intrahepatic portosystemic shunts (TIPS), a modified
      Sugiura procedure and TIPS plus a modified Sugiura procedure were compared to
      evaluate their clinical results in treatment of portal hypertension. METHODS:
      Ninety patients with portal hypertension respectively underwen TIPS (group I, n =
      30), a modified Sugiura procedure (group II, n = 30) and TIPS plus a modified
      Sugiura procedure (group III, n = 30). The rates of rebleeding and
      encephalopathy, and the mortality of patients with portal hypertension were
      observed. RESULTS: The early postoperative complications were observed in 23.33%
      of the patients in group I, in 30.0% of those in group II, and in 20.0% of those
      in group III. The early postoperative rates of rebleeding were 6.67% in group I,
      10% in group II, and 0% in group III. Hepatic encephalopathy was seen in 16.67%
      of the patients in group I, 0% in group II and 13.33% in group III. The early
      mortality was 3.33% in group I. During follow-up for 1 - 36 months, the rates of
      rebleeding were 34.48% in group I, 33.33% in group II, and 3.33% in group III.
      The rates of encephalopathy and mortality were respectively 17.20% and 20.69% in
      group I, 3.33% and 13.33% in group II, 3.33% and 3.33% in group III. The shunt
      patency in group III was higher than that in group I. CONCLUSION: Combination of
      TIPS and a modified Sugiura procedure can be effective to prevent and treat
      variceal bleeding.

PMID- 11831997
TI  - [The role of nitric oxide in the pathogenesis of portal hypertension].
AB  - OBJECTIVE: To investigate the role of nitric oxide in the pathogenesis of portal
      hypertension. METHODS: We measured the portal venous pressure of 75 patients via
      a catheter and detected the levels of plasma endotoxin and NO(2)(-)/NO(3)(-).
      RESULTS: The mean levels of plasma endotoxin and NO(2)(-)/NO(3)(-) (0.249 +/-
      0.112 Eu/ml and 55.9 +/- 26.2 micromol/L) in portal hypertensive patients were
      significantly higher than those in the controls, and the highest values were
      observed in the portal venous blood. The mean portal venous pressure of the
      portal hypertensive patients was 35.5 +/- 4.4 cm H(2)O and was positively
      correlated with the levels of NO(2)(-)/NO(3)(-) (n = 25, r = 0.55, P < 0.01).
      Positive correlation existed between them during the postoperative period (r =
      0.57, P < 0.05). There was a negative correlation between the levels of albumin
      and NO(2)(-)/NO(3)(-) (n = 75, r = -0.35, P < 0.01), and the mean levels of
      NO(2)(-)/NO(3)(-) were 72.4 +/- 20.3 micromol/L in the patients with ascites,
      much higher than those (50.3 +/- 21.0 micromol/L) without ascites. CONCLUSIONS:
      The levels of plasma endotoxin and nitric oxide were elevated in patients with
      portal hypertension, and NO might play an important role in the abnormal
      elevation of portal venous pressure and the damage to liver function.

PMID- 11831999
TI  - [Non-cirrhotic portal hypertension associated with autoimmune disease].
AB  - OBJECTIVE: To summarize the cases of non-cirrhotic portal hypertension associated
      with autoimmune disease, review the literature and introduce the clinical and
      pathological features of the syndrome. METHODS: Six female patients treated,
      between 1983 and 1998 had no history of hepatitis. Variceal bleeding occurred in
      5 patients. One patient received sclerotherapy and operation was performed in 3
      patients for variceal bleeding. Four patients were subjected to liver biopsy.
      RESULTS: Liver dysfunction of these patients remained normal and variceal
      bleeding didn't reccur after therapy. Liver biopsy showed nodular regenerative
      hyperplasia without fibrous septa. CONCLUSIONS: Non-cirrhotic portal hypertension
      associated with autoimmune disease is a rare syndrome, characterized by
      significant portal hypertension as well as histological evidence that cirrhosis
      is absent. Prevention and treatment of variceal bleeding is very important.

PMID- 11832000
TI  - [Germline LKB1 gene mutation screening in 4 Chinese Peutz-Jeghers syndrome
      pedigrees].
AB  - OBJECTIVE: To evaluate the frequency and nature of LKB1 gene germline mutations
      in 4 large Chinese Peutz-Jeghers syndrome pedigrees. METHODS: Four Chinese Peutz
      Jeghers syndrome pedigrees were investigated. Two patients and 1 normal adult
      from each pedigree were selected, and genomic DNA from peripheral blood was
      extracted. The 9 exons of LKB1 gene were amplified by PCR. The products were
      tested by SSCP and abnormally shifted bands were sequenced. If there was no
      positive finding in any pedigree, the entire exons were sequenced. RESULTS: The
      same 842 C deletion of LKB1 gene frame-shift mutations was found in 2 pedigrees,
      which resulted in truncated protein. No exon variant was found in the left 2
      pedigrees. CONCLUSIONS: LKB1 gene germline mutation is an important molecular
      pathogen of Peutz-Jeghers syndrome. 842 C deletion is a possible mutation hotspot
      and might be a common-ancestor mutation characteristic of Chinese.

PMID- 11832001
TI  - [Annular constriction of popliteal vein for treating severe venous
      insufficiency].
AB  - OBJECTIVE: To study the mechanism and therapeutic effects of annular constriction
      for severe venous insufficiency of legs. METHODS: Annular constriction of
      popliteal vein was performed by Gore-Tex vascular graft in 82 patients. Among
      them, 78 patients had deep venous valve insufficiency of legs (III, IV degree), 2
      postphlebitic syndrome, and 2 valve absence of deep vein. Under normal
      respiration and breath holding, venous pressure was measured at the proximal and
      distal part from the constricting site. RESULTS: Great difference was noted in
      the venous pressure between the proximal and distal part from the constricting
      site. The pressure was (9.4 +/- 4.5) mm Hg, (41.2 +/- 28.1) mm Hg at calm and
      (32.4 +/- 16.2) mm Hg, (41.2 +/- 28.1)mm Hg at breath holding (P < 0.01).
      Symptoms disappeared or released after operation. Ulcer healed in all patients.
      Venous pressure decreased by over 60%. Pressure recovery time was over 22
      seconds. There was no reflux distal to the constricting site. Deep venous
      angiography and color Doppler showed an effect similar to venous valve.
      CONCLUSION: Annular constriction is effective in treating severe venous
      insufficiency of legs.

PMID- 11832002
TI  - [Diagnosis and surgical treatment of temporal lobe epilepsy].
AB  - OBJECTIVE: To discuss the diagnosis and surgical treatment of temporal lobe
      epilepsy. METHODS: From 1995 to 1998, 30 patients with intractable mesial
      temporal lobe epilepsy were identified by EEG and MR. Among them, 15 patients
      underwent anterior temporal lobectomy, while another 15 patients accepted
      selective amygdalahippocampectomy. The results of operation and follow-up were
      analyzed. RESULTS: As to seizure outcome, all patients were benefited from
      surgery. Surgical result was satisfactory in 18 patients, notable in 11, and good
      in 1. There was no complication. CONCLUSIONS: MR is beneficial for the
      localization of epileptic foci. Operation is an effective way for the treatment
      of temporal lobe epilepsy. Selective amygdalohippocampus is the first choice for
      medial temporal lobe epilepsy. Transzygmatic-temporal lobe base approach improves
      the safety of operation.

PMID- 11832003
TI  - [Dural arterovenous fistula involving cavernous sinus].
AB  - OBJECTIVE: To study the pathogenesis and treatment of dural arteriovenous
      fistulas (DAVFS) involving the cavernous sinus. METHODS: 32 cases were embolized
      with particle by microcatheterization via endovascular approach and ervation by
      digital substraction angiography. Of the 32 cases, 14 were embolized by
      microsoils through superior petrosal sinus approach into the cavernous sinus.
      RESULTS: In 28 of the 32 cases the fistulas were completely embolized
      angiographically. The fistulas were partly embolized in 4 of the 32 cases. The
      carotid artery was compressed for 6 months. One week later, the fistula
      disappeared angiographically. No fistulas were found during the follow-up for 6
      months to 8 years. CONCLUSION: Endovascular treatment of DAVFS involving the
      cavernous sinus is effective.

PMID- 11832004
TI  - [Transoral microsurgical treatment of craniocervical malformation].
AB  - OBJECTIVE: To discuss transoral microcervical treatment of 16 patients with
      craniocervical malformation. METHODS: Perioperative treatment including
      antibiotics, tracheotomy, intravenous nutrition was used in 16 patients. RESULTS:
      Eight patients had basilar impressions, 3 chronic atlantoaxial dislocation and 2
      odontoid fracture, 2 lower clivus chordoma, and 1 granuloma in the ventral part
      of the medulla oblongata. Three patients received bone graft. Follow-up for 6 -
      36 months showed that 14 patients resumed normal life but 1 died. CONCLUSIONS:
      Pre-craniocervical malformation can be treated by transoral approach
      microsurgically. Understanding microanatomy of this approach can reduce
      postoperative morbidity and complications. Perioperative treatment can prevent
      incision infection. Prevention of intraoperative CSF leakage must be
      emphasized.Bone graft can make craniocervical spine stable.

PMID- 11832005
TI  - [Surgical correction of complete atrioventricular septal defect with tetralogy of
      Fallot].
AB  - OBJECTIVE: To report the surgical correction of complete atrioventricular septal
      defect with tetralogy of Fallot (AVSD-TOF). METHODS: Six consecutive patients
      aged 3 - 9 years underwent correction of complete AVSD-TOF. The two-patch
      technique for atrioventricular septal defect was used. The ventricular septal
      defect was closed through a right ventriculotomy and right atriotomy in each
      case. The commissure between the superior and inferior bridging leaflets of the
      left portion of the common atrioventricular valve was closed in each patient.
      RVOT obstruction was relieved by a transannular autologous pericardium with
      monocuspid valve. RESULTS: Postoperative complications included respiratory
      failure in 1 patient, low cardiac output syndrome in 1, and MOF in 1. There was
      one mortality because of MOF in the early postoperative period. Five survivors
      were followed up from 6 months to 5.5 years (mean 2.3 years). There was no late
      mortality and only one patient had mild left atrioventricular valve
      regurgitation. NYHA cardiac function was class I in 4 patients and class II in 1.
      CONCLUSIONS: AVSD-TOF can be corrected using the two-patch technique and closure
      of the ventricular septal defect through a combined approach using a right
      ventriculotomy and right atriotomy. Routine closure of the commissure of the left
      portion of the atrioventricular valve results in a low incidence of
      regurgitation. Good functional result can be achieved in most patients
      postoperatively.

PMID- 11832006
TI  - [Treatment of ureteric lithioasis with ureteroscope: report of 234 patients].
AB  - SUBJECT: To sum up the experience in the treatment of ureteric lithioasis with
      ureteroscope. METHODS: From January. 1991 to November 1998 234 patients with
      ureteric lithiasis were treated with lithotripsy of ureteroscopy. RESULTS: 185 of
      234 the patients (79%) were successfully treated with lithotripsy of
      ureteroscopy. Three of the patients (1.3%) had operative complications
      (ureterperforation 2 patients and ureteral mucosa avulsion in 1). CONCLUSIONS:
      Lithotripsy of ureteroscope is one of the effective methods in the treatment of
      ureteric lithiasis, especially in the lower part of ureters.

PMID- 11832007
TI  - [Clinical types of pheochromocytom].
AB  - OBJECTIVE: To improve the diagnosis and treatment of pheochromocytoma. METHODS:
      90 patients with pheochromocytomas were treated from June 1987 to August 1998.
      These patients showed extra-adrenal (14 patients), non-symptomatic (5), recurrent
      (8), malignant (15), bilateral or multiple (4), and familial or MEN-IIA (5).
      RESULTS: One patient with malignant extra-adrenal pheochromocytoma showed
      extensive metastasis. All the patients except this patient were confirmed
      pathologically. 36 patients were followed up for 5 months - 10 years. Eight
      patients had recurrence and 3 showed malignancy. CONCLUSIONS: Open surgery is an
      effective method for pheochromocytoma. Preoperative preparation must be
      sufficient to make the operation safe. Recurrent pheochromocytomas are not
      malignant in nature, but they have considerable malignant tendency and should
      undergo intensive surveillance and regular examinations. Familial
      pheochromocytomas are bilateral or multiple. They could develop into secondary
      medullar thyroid carcinoma in the meantime.

PMID- 11832008
TI  - [Microcirculation of thoraco-acromial flaps: monitoring and clinical
      application].
AB  - OBJECTIVE: To monitor the microcirculation of thoraco-acromial flaps. METHODS:
      The microcirculation in 12 thoraco-acromial flaps was monitored continuously by
      laser Doppler flowmetry (LDF). RESULTS: The microcirculatory changes in thoraco
      acromial flaps were divided into two phases: rapid rising (2 - 4 days after
      operation) and plateaurising (4 - 7 days after operation). PU values were 7.4 +/-
      2.0, 7.6 +/- 2.3 and 7.3 +/- 1.6. CONCLUSIONS: In division of the thoraco
      acromial flaps within the plateau, the value (PU) returned to or exceeded 50% of
      that before application of the tourniquet. All flaps survived. The time of
      division was decreased to 6 - 8 after operation days.

PMID- 11832009
TI  - [Anatomical basis of autonomic nerve-preserving radical resection for rectal
      cancer].
AB  - OBJECTIVE: To clarify anatomical basis of autonomic nerve-preserving radical
      resection for rectal cancer. METHOD: Of 10 cadavers, 4 were male and 2 female.
      Four had hemisected pelvis in the mid-sagittal plane without damaging the
      retrorectal anatomy. All stages of each dissection were recorded
      photographically. RESULTS: Hypogastric nerves were identified. The superior
      hypogastric plexus is the direct extension of the aortic plexus below the aortic
      bifurcation. It lies immediately behind the peritoneum and descends over the
      anterior surface of the 5th lumbar vertebra in the retroperitoneal tissue. The
      superior hypogastric plexus ends by bifurcating into the right and left
      hypogastric nerves. The two hypogastric nerves diverge from each other at about
      the level of the sacral promontory and run down and forward along the walls of
      the pelvis in the lamina of the pelvic fascia closest to the peritoneum. Both of
      them are strong fibres with white-grey and reticular appearance and well located
      just below and close to the aortic bifurcation. And after bifurcation each of
      them also gives rise to several branches. But it is difficult to identify the
      pelvic splanchnic nerves in complete samples. In mid-sagitted samples they take
      origin from the second to fourth sacral ventral rami just after the sacral nerves
      have emerged from the pelvic sacral foramina. They always form plexus at the
      lateral ligament and are crossed by middle rectal artery. CONCLUSIONS: It is not
      very difficult to preserve the hypogastric nerves to spare functions in resection
      for rectal cancer to the anatomical knowledge of the pelvic autonomic nerves.
      When the pelvic splanchnic nerves are to be preserved, dissection must be
      cautious at the level of the lateral ligment on the side of nerve-preservation.
      The operation should be performed near the rectum as close as possible to achieve
      functional preservation.

PMID- 11832010
TI  - [Clinical application of magnetic resonance angiography in the body].
AB  - OBJECTIVE: To identify the accuracy and reliability of magnetic resonance
      angiography (MRA) in evaluating patients with vascular lesions in the body.
      METHODS: 171 patients with suspected vascular lesions in the body were examined
      by MRA and compared with the results of X-ray angiography (XRA) or operation.
      RESULTS: MRA showed abnormal vein in 12 patients and normal in 6 corresponding to
      XRA or operation. MRA revealed aneurysm in 54 patients: aortic dissection (26),
      aortic aneurysm (15) and peripheral aneurysm (13). Two peripheral aneurysms could
      not only be found by MRA. The sensitivity of MRA was 97% for aneurysm lesions.
      The sensitivity of MRA in the diagnosis of suspicious peripheral artery stenosis
      in 84 patients was 95%, the specificity 89%, and the accuracy 92% in comparison
      with those of XRA and operation. CONCLUSION: MRA is accurate and reliable in
      evaluating vascular lesion in the body and can replace XRA in many cases.

PMID- 11832011
TI  - [Radiographic studies of cervical spine motion range in normal Chinese subjects
      with computer-assisted image analysis: full flexion and extension].
AB  - OBJECTIVES: To study the degenerative regularity of normal Chinese cervical spine
      by observing the motion range of full cervical flexion and extension, and to
      provide evidences for further investigation of cervical segmental instability.
      METHODS: 764 X-ray plain films of full cervical flexion and extension in 382
      normal Chinese subjects (214 were male and 168 female) were investigated using
      self-designed cervical X-ray image analysis system. The subjects within the same
      sex group were divided into three groups according to the age: group A (20 years
      to 39 years), group B (40 years to 59 years) and group C (60 years to 76 years).
      During the full cervical flexion and extension motion, total intervertebral
      motion range (from C(2) - C(3) to C(6) - C(7)) and intervertebral motion range at
      each level were major parameters. RESULTS: The range of total intervertebral
      motion showed much greater mobility in group A than in group B and group C (P <
      0.01) but no statistically significant difference between group B and group C (P
      > 0.05). The range of intervertebral motion was maximal at C(5) - C(6) in group
      A. The place of maximal motion shifted to the C(4) - C(5) in both group B and
      group C. C(2) - C(3) showed minimal mobility in all three groups. There was no
      statistically significant difference (P > 0.05) between male and female.
      CONCLUSIONS: The motion range and degenerative regularity of normal Chinese
      cervical spine were similar in either sex. The range of total intervertebral
      motion (from C(2) - C(3) to C(6) - C(7)) had a tendency to decrease rapidly and
      then became steady with age. For the range of intervertebral motion, the place of
      maximal motion shifted to the higher level with age from C(5) - C(6) in group A
      to C(4) - C(5) in group B and group C.

PMID- 11832012
TI  - [Experimental and clinical study of gentamicin-loaded chitosan drug delivery
      system].
AB  - OBJECTIVE: To conduct a clinical study and release test for a drug delivery
      system (DDS) of gentamicin-loaded chitosan bar in attempt to extend its clinical
      application. METHODS: The diffusion behavior of gentamicin from chitosan DDS was
      detected using in vitro, in vivo release test. Eighteen cases of chronic
      osteomyelitis were treated by chitosan DDS. The clinical result was evaluated by
      wound healing and clinical and X-radiographic manifestation. RESULTS:
      Concentration of gentamicin about 926.7 microg/bar/day was released from DDS
      within the first 24 hours by in vitro diffusion test. It fell and sustained by
      25th day with rate of 4.0 microg x bar(-1) x day(-1). In in vivo study, serum
      gentamicin concentration reached its peak level (0.92 microg/ml) 24 hours after
      implantation. No increase was observed in the concentration of BUN and Cr. In all
      bone tissue around the bar, 8 weeks after oderation the gentamicin concentration
      exceeded the minimum inhibitory concentration for the common causative organisms
      of osteomyelitis. The follow up time was 24.8 months (6 - 34). The initial cure
      ratio was 2/18 and the recurrence ratio zero. CONCLUSION: The gentamicin-loaded
      chitosan bar is a good DDS with sustained antibiotic effect in vivo and in vitro.
      It is an effective method for the treatment of bone infection.

PMID- 11832013
TI  - [Effect of protein expression on antisense c-myc and PCNA for vascular smooth
      muscle cells].
AB  - OBJECTIVE: To study the methods of inhibiting proliferation of vascular smooth
      muscle cells (VSMCs), we observed the change of protein expression after using
      antisense c-myc, PCNA for VSMCs. METHODS: The sense, antisense, and mismatched
      oligomers for c-myc or PCNA were individually delivered to the cultured VSMCs.
      Using Western blot, immunohistochemistry assay and image analysis system, we
      observed the change of c-myc and PCNA protein expression in the VSMCs. RESULTS:
      Antisense c-myc, PCNA at concentration of 10 micromol/L can successfully inhibit
      the expression of c-myc, PCNA protein in the VSMCs (P < 0.05), but the sense and
      the mismatched do not have this effect (P > 0.05). CONCLUSION: The data suggested
      that the antisense c-myc, PCNA could attenuate the protein expression of c-myc,
      PCNA, and it is an effective method for the inhibition of VSMCs hyperplasia.

PMID- 11832014
TI  - [Gil-Vernet anti-reflux operation by united application of television laparoscopy
      and vesicourethral laparoscopy].
AB  - OBJECTIVE: To discuss the possibility of united application of television
      laparoscopy and vesicourethral laparoscopy in Gil-Vernet operation. METHODS: The
      animal model of vesicourethral reflux (VUR) was established using rabbits. The
      Gil-Vernet operation was carried out by united application of television
      laparoscopy and vesicourethral laparoscopy. RESULTS: The VUR model was
      successfully established in 13 rabbits, and the reflux was successfully cured by
      microsurgical methods. CONCLUSIONS: This method had the advantages of television
      laparoscopy, vesicourethral laparoscopy and the Gil-Vernet such as no dissection
      of inner part of ureter-bladder wall, small wound, less bleeding, fast recovery,
      less complication and possible repetitive operation. It can be used in ill
      children with VUR.

PMID- 11832015
TI  - [Changes of blood circulation of the extremity with tibia shaft defects treated
      with external fixation].
AB  - OBJECTIVE: To study external skeletal fixation for long tubular bony defect by
      end to end compression with lengthening (EECL) and segmental bone transport by
      lengthening (STBL). METHODS: About 20% - 30% of the original length was resected
      from the middle shaft of the tibia in 10 goats of 1 - 2 years of age. The bony
      defect ends were shortened step by step with the sulcated half-ring external
      fixator. Changes of the blood flow of the distant extremity were measured with
      pulse-dopplar monitor, reference blood flow, and angiograph. RESULTS: The blood
      flow of the distant extremity was not affected when bony defect was less than 15%
      of the original length. Blood circulation disorder would appear in the distant
      extremity when bony defect ranged from 15% to 20% of the original length. The
      distant extremity would necrose because of obstruction of blood circulation when
      bony defect was more than 20% of the original length. CONCLUSIONS: EECL can be
      recommended if bony defect is less than 15% of the original length. SBTL might be
      the only feasible way if bony defect is more than 20% of the original length. If
      bony defect is within 15% and 20%, EECL should be applied with great care while
      watching the extremity circulation with pulse-Dopplar monitor.

PMID- 11832016
TI  - [Dynamic changes in dermal cell cycles, contents of hydroproline and ratios of
      collagen type I/III in the burned wound].
AB  - OBJECTIVE: To study the dynamic changes in the dermal cell cycles contents of
      hydroproline and ratios of collagen type I/III in the burned wound. METHODS: The
      dermal cell cycles, contents of hydroproline, ratios of collagen type I/III and
      pathologic changes were dynamically observed in 48 deep partial burn rats (TBSA
      10%), attempting to investigate the process of deep partial burn wound healing.
      RESULTS: The percentage of S-phase reached the highest point on PBD 10. On PBD21,
      it was still significantly higher than that of normal group. OHP increased
      gradually after burn, and peaked on PBD14. On PBD21, the level of OHP was still
      significantly higher than that of normal group. The ratios of collagen type I/III
      decreased gradually and significantly lower than those of the normal group after
      burn. The strips of WBC infiltrating into wound were observed on PBD3, 7 and 10.
      On PBD 14, a large number of regenerative epidermal cells crept over wound
      surface. CONCLUSIONS: The inflammation is obvious from PBD3 to PBD10. The
      proliferation of dermal cell and the synthesis, deposition of new collagen are
      predominant from PBD10 to PBD14, and the repair of dermis is not complete on
      PBD21. The proliferation and migration of epidermal cells are major activities
      from PBD14 to PBD21.

PMID- 11832017
TI  - Bilateral pallidotomy for treatment of idiopathic Parkinson's disease.
AB  - OBJECTIVE: To clarify the benefits and risks of patients undergoing bilateral
      posteroventral pallidotomy (BPVP) for patients with idiopathic Parkinson's
      disease (PD) and the differences between contemporaneous BPVP (CBPVP) and staged
      BPVP (SBPVP). METHODS: Twenty patients underwent microelectrode-guided CBPVP and
      26 SBPVP for bilateral PD symptoms. The data were retrospectively reviewed.
      Unified Parkinson's Disease Rating Scale (UPDRS) was used to evaluate the effects
      of these operations. RESULTS: BPVP, either CBPVP or SBPVP, significantly improved
      patients' bilateral PD symptoms (P < 0.001). The improvement was consistently
      higher in "off" state than in "on" state. No statistical difference was observed
      in the improvement percentages of CBPVP, SBPVP1 and SBPVP2. CBPVP contributed
      greatly to L-dopa induced side effects (part IV). BPVP, SBPVP1, and SBPVP2
      significantly improved cardinal parkinsonian signs but no difference was found
      among them. One patient after CBPVP developed hypophonia and swallowing problem,
      while 2 patients after SBPVP sustained hypophonia. These conditions were improved
      3 months later. CONCLUSIONS: BPVP may significantly improve bilateral signs of
      PD. It is safer than bilateral thalamotomy. CBPVP is applicable to some patients.
      BPVP may not cause mental impairment but shows a higher incidence rate of
      hypophonia. The practice of BPVP requires a refined surgical technique and a
      better understanding of pathophysiology of the basal ganglia.

PMID- 11832018
TI  - [Damage to intra- and extrahepatic bile duct after hepatic artery embolization].
AB  - OBJECTIVE: To study the pathogenesis, treatment and prevention of bile duct
      damage arising from hepatic artery embolization. METHODS: Five patients with
      intra- and extrahepatic biliary damage resulting from hepatic artery
      embolization. Of these patients, 4 were due to hepatic artery embolization for
      hepatic haemangioma, and 1 was due to injecting TH (methacrylate) compound into
      the hepatic artery during operation. The hepatic artery was injected with ethanol
      so as to evaluate liver damage in experimental rats. RESULTS: All patients were
      found to have damage to intra- and extrahepatic bile duct at the hilum with
      biliary hepatocirrhosis; 4 of them received intrahepatic bile duct jejunal
      anastomosis and bile duct stent. Experiment result revealed obliteration of the
      bile duct and necrosis of the liver around the portal tract area. CONCLUSIONS:
      Arterial embolization of hepatic haemangioma may cause severe biliary damage.

PMID- 11832019
TI  - [Acute mesenteric vein thrombosis: diagnosis and management].
AB  - OBJECTIVE: To evaluate the progress in diagnosis and management of acute
      mesenteric vein thrombosis (AMVT). METHODS: Fifteen patients with AMVT treated
      from January 1983 to November 1998 were reviewed retrospectively. They were 7 men
      and 8 women, aged on average 42 years. The duration from onset of symptoms to
      admission was 24 - 168 hours (mean 84 hours). RESULTS: Six patients were
      diagnosed before operation, while 9 during laparotomy. Two patients received
      conservative treatment and the rest underwent surgery. The average length of
      bowel resection was 300 cm. All the patients received anticoagulation therapy
      with heparin immediately after operation. Local thrombolytic therapy was given to
      4 patients. Four patients died in hospital and two had sequelae of short bowel
      syndrome. CONCLUSIONS: AMVT is rare but a potentially lethal emergency disease.
      Early diagnosis, anticoagulation and appropriate surgical approach are essential
      to improve the prognosis. It is important to keep vigilance for AMVT in the
      patients in the hypercoagulation status, especially when the symptoms are
      inconsistent with abdominal signs. Color-US and CT appear to be sensitive in the
      diagnosis of this condition. Local thrombolytic therapy will be effective. Second
      look is a necessarily procedure for reserving the bowel that may be alive.
      Laparoscopy technique will play an important role in the diagnosis and treatment
      for AMVT.

PMID- 11832020
TI  - [Hemorrhagic shock increases the occurrence of bacterial translocation].
AB  - OBJECTIVE: To determine whether hemorrhagic shock (HS) increases the occurrence
      of bacterial translocation (BT). METHODS: 100 patients were divided into 4
      groups: control group (group I, 34 patients); group with hemorrhagic shock (HS)
      caused by closed blunt abdominal trauma (group II, 23); group caused by closed
      blunt abdominal trauma without HS (group III 15); and group with HS caused by
      intra-abdominal viscus hemorrhage (group IV 28). Preoperative and postoperative
      samples were taken from peripheral blood, visceral peritoneal swab, portal vein
      blood, ileal mesenteric lymph node, liver and spleen biopsy respectively for
      aerobic and anaerobic culture. RESULTS: The positive culture rates of these
      groups were 6%, 65%, 13%, 68% respectively. The difference between the control
      and experimental groups was significant(P < 0.05). The difference was also
      significant between group I and II and between I and IV (P < 0.01), whereas it
      was not significant between I and III, and between II and IV (P > 0.05).
      CONCLUSION: HS increases the occurrence of BT.

PMID- 11832021
TI  - [Endoluminal stent-graft repair of aortic aneurysms].
AB  - OBJECTIVE: To study the clinical value of the treatment of aortic aneurysms with
      endovascular stent-graft prosthesis. METHODS: After a unilateral surgical
      arteriotomy, Talent, Vanguard and Chinese stent-graft were advanced through the
      femoral arteries and placed in the proper position of the aneurysm sac under X
      ray fluoroscopic guidance. RESULTS: Four patients with descending aneurysm, 1
      patient with abdominal aortic aneurysm (AAA) involving the renal artery, superior
      mesenteric artery and celiac artery, and 1 patient with right common iliac artery
      aneurysm received straight stent-grafts. Five patients with infrarenal AAA
      received bifurcated stent-grafts. CT and MRA were performed during a follow-up of
      3 - 19 months. Aortic aneurysms were completely excluded from the circulation.
      Five patients prolonged fever was noted and 1 patient was found to have a leakage
      3 months later, and hemiplegia in 1 after procedure. CONCLUSIONS: Endovascular
      treatment of aortic aneurysm is technically feasible and can effectively exclude
      aortic aneurysms from the circulation. Endoluminal repair may serve as an
      interventional strategy to treat aneurysm, especially in patients at high
      surgical risk, but long term effect needs further study.

PMID- 11832022
TI  - [Anterior corpectomy combined with cervical spine locking plate for treatment of
      multilevel cervical spondylotic myelopathy].
AB  - OBJECTIVE: To study the value of cervical spine locking plate (CSLP) combined
      with anterior corpectomy in treating multilevel cervical spondylotic myelopathy
      (CSM). METHODS: In 55 CSM patients, 36 were male and 19 female, aged on average
      51.5 years. The duration of illness was 13 months on average. Pathological
      segments in 47 patients included two functional segments and in 8 three
      functional segments. All patients were treated with anterior corpectomy and self
      iliac bone graft and CSLP fixation. RESULTS: 51 patients were followed up for 26
      months on average. All grafting bones got solid fusion in 12 to 16 weeks
      postoperatively. Intervertebral spaces were restored after operation. The
      physiological curve of the cervical spine was good. The effective rate of
      operation was 94.1% (48/51) and the excellent rate 78.4% (40/51). The JOA score
      rose from 8.3 points before operation to 14.1 points after operation.
      CONCLUSIONS: Anterior corpectomy and osteosynthesis of multilevel cervical
      spondylotic myelopathy are indicated for CSLP fixation. CSLP in the treatment of
      cervical spine instability is prospective.

PMID- 11832023
TI  - [Surgery for lung cancer complicated by bronchial asthma].
AB  - OBJECTIVE: To assess surgery for lung cancer complicated by bronchial asthma.
      METHODS: Lung hilum denervation was performed for asthma during radical resection
      of lung cancer. One patient with peripheral bronchogenic carcinoma in the right
      upper lobe underwent upper lobectomy and extensive dissection of lymph-nodes.
      Simultaneously, lung hilum denervation was done by complete amputation of the
      sympathetic and parasympathetic nerves around the lung hilum. Another patient
      with central bronchogenic carcinoma in the left upper lobe underwent lung
      autotransplantation. Pneumonectomy was performed, and the tumor parts of the lung
      were resected subsequently and the preservable parts of the lung were replanted
      into the bed of the upper lobe. RESULTS: Follow-up showed that the two patients
      had been alive with tumor free for 80 months and 17 months respectively and the
      time of postoperative mechanical ventilation was 4 and 18 hours. The frequency of
      asthma paroxysm decreased and the severity attenuated. Parameters of blood gas
      and lung function were improved. CONCLUSIONS: The poor lung function caused by
      asthma should not be regarded as a contradiction for the removal of lung cancer.
      Complete denervation around the lung hilum during the radical resection of lung
      cancer may contribute to the better treatment of lung cancer and asthma.

PMID- 11832024
TI  - [Lung cancer: new staging system and prognosis].
AB  - OBJECTIVE: To evaluate the rationality the revised international system for
      staging lung cancer and its relationship with prognosis. METHODS: Between January
      1961 and December 1988, 946 patients were subjected to removal of lung cancer and
      the data were analyzed using life-table, Log-rank test, and Cox regression model.
      Twenty-nine prognostic factors influencing the survival rate were evaluated with
      SAS6.12 software. The survival rate was calculated according to the two different
      staging systems. The revised system for staging lung cancer was evaluated.
      RESULTS: The factors influencing prognosis after surgical treatment of lung
      cancer were as follows: P-TNM staging, metastatic lymph nodes, radical or
      palliative resection, tumor size, and different cell types. The 5-year survival
      rate of patients with stage IA, IB, IIA, IIB, IIIA, IIIB was 68.4%, 59.5%, 44.8%,
      36.5%, 26.3%, and staging 24.8%, respectively (IIIA and IIIB P > 0.05; other
      stages P < 0.05). CONCLUSIONS: The revised system for lung cancer is more
      rational and objective to estimate prognosis and direct treatment. But it should
      be revised further.

PMID- 11832025
TI  - [Transposition of bilateral pedicled adrenal gland for the treatment of Cushing's
      disease].
AB  - OBJECTIVE: To study the therapeutic method of Cushing's disease. METHODS: 16
      patients with Cushing's disease were treated by transposition of bilateral
      pedicled adrenal gland into the dorsal subcutaneous tissues. RESULTS: These
      patients were followed up for 4 to 48 months. No relapse was observed and 3
      patients with hypoadrenocorticism were given small doses of steroid. CONCLUSIONS:
      This procedure may be a rational and satisfactory technique for the treatment of
      Cushing's disease.

PMID- 11832026
TI  - [Simultaneous nasal reconstruction and facial defect repair using expanded
      forehead flap].
AB  - OBJECTIVE: To improve the method for the repair of facial defect using expanded
      forehead flap. METHODS: 10 patients were treated with the expanded forehead flap
      for total nose reconstruction and repair of facial defects. The expanded flap was
      divided two parts: the supratrochlear vessels for nasal reconstruction and the
      frontal branch of the superficial temporal vessels for facial defects. The
      periorbital or zygomatic area, the upper or lower lip. The defect of the forehead
      donor site was directly closed. RESULTS: Nasal reconstruction and repair of
      facial defects were satisfactory in all patients. CONCLUSION: Nasal
      reconstruction and simultaneous repair of facial defects extend the scope of use
      of expanded forehead flap.

PMID- 11832028
TI  - [Influence of androgen on Bcl-2 mRNA expression in BPH tissue].
AB  - OBJECTIVE: To study the expression of Bcl-2 mRNA in BPH tissue and the influence
      of androgen. METHODS: The circulating testosterone level of BPH patients and rats
      was decreased by administration of medroxyprogesterone and stilbestrol as well as
      castration. Using RNA dot blot hybridization technic, we detected the Bcl-2mRNA
      expression in human BPH tissue and rat prostate under different level of
      androgen. RESULTS: The average dot IOD (integrated optical density, IOD) value
      ratio of the untreated patient group to the treated group was 1.71 (P < 0.01).
      There was an decrease of intensity of Bcl-2 mRNA expression in the latter group
      compared with the former group. The ratio of the normal rat prostates to the
      castrated rat prostates was 1.28 (P < 0.05). The Bcl-2 mRNA expression was
      decreased after castration. CONCLUSIONS: The expression of Bcl-2 plays a role in
      the development of BPH. The decrease of prostatic cell death is important in the
      BPH pathogenesis. Apart from promoting the proliferation of prostatic epithelia
      and stroma cells, androgen might prohibit apoptosis by increasing the expression
      of Bcl-2 in BPH development.

PMID- 11832027
TI  - [Genes of micrometastasis in bone marrow of patients with colorectal cancer].
AB  - OBJECTIVE: To detect the gene of micrometastasis in bone marrow of patients with
      colorectal cancer. METHODS: PCR-SSCP/silver stain technique was used to find out
      the metastatic cancer cells in 51 bone marrow samples in different time. RESULTS:
      The total positive rate of mutations of p53 and K-ras in bone marrow was 37.25%
      before operation. The incidence of mutations was obviously correlated with Duke's
      stage and lymphatic metastasis. After postoperative chemotherapy mutation in 11
      patients turned to be negative. CONCLUSIONS: Detection of micrometastasis in bone
      marrow may contribute to early diagnosis of blood stream metastasis of colorectal
      cancer.

PMID- 11832029
TI  - [Expression of Fas ligand in urogenital malignant cell lines and renal cell
      carcinoma].
AB  - OBJECTIVE: To explore the expression of Fas ligand in urogenital malignant cell
      lines and renal cell carcinoma. METHODS: With immunocytochemistry and reverse
      transcription-polymerase chain reaction (RT-PCR), we detected the expression of
      Fas ligand (FasL) in 6 urogenital malignant cell lines, bladder carcinoma cell
      lines (T(24), EJ, BIU-87), renal cell carcinoma cell lines (GRC-1, RCC-949),
      prostatic carcinoma cell line (PC-3M), and 10 cases of renal cell carcinoma.
      RESULTS: The expression of FasL was detected in 3 (BIU-87, RCC-949, GRC-1) of the
      6 urogenital malignant cell lines with immunocytochemistry, and 4 (BIU-87, RCC
      949, GRC-1, PC-3M) of 6 urogenital malignant cell lines with RT-PCR method. No
      expression of FasL was detected in bladder carcinoma cell lines T(24) and EJ.
      Eight of 10 renal cell carcinoma tissues positively expressed FasL mRNA.
      CONCLUSIONS: FasL can express in urogenital malignant cell lines and renal cell
      carcinoma.

PMID- 11832030
TI  - [Photodynamic therapy of hematoporphyrin derivative on human pancreatic carcinoma
      cell lines].
AB  - OBJECTIVE: To observe the effect of photodynamic therapy (PDT) on human
      pancreatic carcinoma cell lines in vitro. METHODS: Two lines of human pancreatic
      carcinoma cell P3 and SW1990 were studied to investigate the killing role of PDT
      with hematoporphyrin derivative (HPD) as photosensitizer and sodium lamp as light
      source. The cultured cells were treated with serial concentrations of HPD
      followed by irradiation of different dosages of visible light, then MTT
      colorimetric assay was applied to measure the relative inhibitory rate of PDT for
      the cells. RESULTS: The relative inhibitory rate of PDT for the cells elevated
      along with the increase in the concentration of sensitizer and dose of light.
      Under the low photodynamic dose, it increased rapidly, and gradually slowed down
      to reach the plateau. Under the same photodynamic dose, significant difference in
      the inhibitory rate between the two lines was observed (P < 0.01), and the LD90
      was also different. CONCLUSIONS: PDT has a significant killing effect on human
      pancreatic carcinoma cell lines in vitro, and its relative inhibitory rate
      appears to be correlated with the dose of sensitizer and light irradiation. The
      sensitivity of the two cell lines to PDT is different.

PMID- 11832032
TI  - [Changes of blood vessels in glucocorticoid-induced avascular necrosis of femoral
      head in rabbits].
AB  - OBJECTIVE: To evaluate the effects of fatty tamponade in medullary cavity
      (serious intramedullary fatty infiltration) on the changes of blood vessels in
      femoral heads during the pathological process of glucocorticoid (GC)-induced
      avascular necrosis (AVM) of the femoral heads. METHODS: The animal model of AVN
      was established with injection of dexamethasone (DEX) at a high dose of 2.5 mg x
      kg(-1) x d(-1) in rabbits. Histopathological and morphological changes of blood
      vessels in the femoral heads were investigated during GC-treatment and after the
      cessation scanning electron microscope, light microscope, and image analysis.
      RESULTS: At the 2nd week of DEX-treatment, the fatty tamponade in the medullary
      cavity appeared in the femoral heads. Intramedullary vascular sinusoids were
      pressed by an excess of lipocytes and became narrow. The impressions of lipocytes
      on the surface of vascular sinusoids were definitely displayed on the vascular
      casts and ink-perfused slides of the femoral heads. These changes were pronounced
      with the prolongation of the treatment and the vascular sinusoids gradually lost
      their characteristics. Image analysis showed that the vascular area in the
      femoral heads continuously decreased. At the 8th week, the effects of fatty
      tamponade were the most marked. Intramedullary vessels became very sparse and the
      vascular area decreased to 1/4 of the controls. At the 6th week after the GC
      treatment cessation, intramedullary fatty infiltration still existed. The blood
      vessels were fine and sparse, and the structural features of vascular sinusoids
      disappeared in the load-bearing regions of the femoral heads. At the 4th week,
      typical osteonecrosis focuses appeared in the femoral heads. The focuses became
      larger and the degree of osteonecrosis was increasing with the time of
      experiment. CONCLUSION: The fatty tamponade in the medullary cavity is one of the
      important pathological factors causing ischemic damage to the femoral heads, and
      plays an important role in the early stage of GC-induced AVN.

PMID- 11832031
TI  - [The attractive effects of nerve regeneration chamber fluid and degenerated nerve
      segments on the growth and the migration of the cocultured dorsal root ganglion
      neuron].
AB  - OBJECTIVES: We intended in this study to investigate the neurotropic effects of
      regeneration chamber fluid (RCF) and the degenerated nerve segments from distal
      of the regeneration chamber on the dorsal root ganglion (DRG). METHODS: The
      capillary model was first tested for its reliability to form concentration
      gradient with a dye being contained in the capillaries. The tissue culture in RCF
      test was divided into two groups each with 8 DRGs implanted in 8 dishes. RCF was
      contained in capillaries inserted down to the bottom of the dishes with their
      lower ends at a distance of about 1 mm to the DRGs in the experimental group, and
      DMEM media was contained in the control group. Segments of degenerated sciatic
      nerve from distal of the regeneration chamber were implanted with DRGs at a
      distance of about 0.5 - 1 mm in the coculturing experiment. DRGs were observed
      for the direction of the growth of the cells and the fibres. RESULTS: While the
      capillary containing the dye was put down to the bottom of the culture dish
      coated with a piece of nylon pad, the red color slowly disseminated with heavier
      staining in the center and lighter staining in the peripheral portion. We believe
      this pattern of shade could simulate the concentration gradient of tropic factors
      in this model. There were significantly more nerve fibres growing from the DRGs
      towards the capillaries in 6 of the 8 dishes in the experimental group after 72
      hours of culture. The tissue and nerve fibers grew evenly in the control group.
      76.5% of all the nerve fibres were growing in the direction facing the
      degenerated nerve segments after 12 hours of coculturing, and only 33.3% of the
      nerve fibres growing in that direction in the control group. Cells from the DRGs
      migrated towards the degenerated nerve segments, yet they tended to avoid the
      normal nerve segments. The migration index of the cells was 0.98 in average in
      the coculturing experiment with the degenerated nerve segments, but only 0.43 in
      average with the normal nerve coculturing. CONCLUSION: The capillary model was
      effective in studying the chemotactic growth of nerve tissue. RCF and the
      degenerated nerve segments had definite neurotropic effects on DRGs tissue.

PMID- 11832033
TI  - [Changes in myelin sheath and axon of spinal cord in X-irradiation injured rats].
AB  - OBJECTIVE: To investigate the X-irradiation effect on the myelin sheath and axon
      of the spinal cord. METHODS: 60 Wistar adult rats receiving hemisection in the
      thoracic spinal cord were made into models of spinal injury. Among these rats, 30
      in the test group received X-irradiation of 35-Gy the day after operation, while
      30 in the control group only received hemisection. Operative spinal cord was
      subjected to immunohistochemistry and hyper-microscopic observation. RESULTS: In
      the test group, injury to the myelin sheath of the upper and lower lesion and the
      number of neuro-fibrotic positive axon increased. In the control group the number
      of myelin sheath below the injured section decreased. Under electronic
      microscope, demyelination was found in the spinal cord and new-born tiny neuro
      fibrotic tracts were seen below the lesion. CONCLUSIONS: X-irradiation can make
      spinal cord demyelinate and promote the increase of neuro-fibrotic positive axon.

PMID- 11832034
TI  - [Adenosine in treatment of rats with spinal cord injury].
AB  - OBJECTIVE: To observe the changes of endogenous extracellular adenosine after
      spinal cord injury (SCI) to rats and the effect of exogenous adenosine on
      extracellular calcium after SCI and post-injury neurological function. METHODS: A
      ventral compression injury model of T13 spinal cord was used, and the
      extracellular fluids were collected consecutively every 20 minutes after injury
      by using microdialysis. Adenosine in the samples was analyzed using high-pressure
      liquid chromatography (HPLC) with u.v. detection. The rats received different
      doses of 2-chloroadenosine (2-CADO), a nonspecific agonist of adenosine
      receptors, by intrathecal injection 15 minutes before injury. The extracellular
      fluid was collected every 10 minutes immediately after injury and the calcium was
      measured using atomic absorption spectrophotometer. Neurological function score,
      inclined plane angle, and histology were observed 24 hours after injury. RESULTS:
      A significant increase of adenosine was found immediately after spinal cord
      injury. The concentration of adenosine peaked at one hour after injury and
      dropped down to the basal level. There was a positive relation between the
      increase of adenosine and the severity of SCI. High dose of 2-CADO can
      significantly significantly inhibit the decrease of extracellular calcium and
      improve the neurological function of injured rats. CONCLUSIONS: Adenosine could
      involve the pathological process of secondary spinal cord injury and might play a
      protective role in SCI.

PMID- 11832035
TI  - [Comparison of atrio-ventricular and total cavo-pulmonary connections versus
      atrio-pulmonary anastomosis for repair of tricuspid atresia in dogs].
AB  - OBJECTIVE: To compare the hemodynamic effect and energy loss of atrio-ventricular
      and total cavo-pulmonary connections versus atrio-pulmonary anastomosis for
      modified Fontan in dogs. METHODS: Fifteen adult mongrel dogs were divided into
      three groups. Group I underwent right atrium to right ventricle (using 50% and
      25% right ventricular chamber, respectively) connection with the flap of valved
      homo-pulmonary artery (modified Bjoerk procedure). Group II underwent total cavo
      pulmonary connection. Group III received atrio-pulmonary anastomosis. Right
      atrium pressure, pulmonary artery pressure, and cardiac output were measured by
      Swan-Ganz catheter. The volumes of the right pulmonary artery, left pulmonary
      artery, superior vena cava and inferior vena cava were measured by
      electromagnetic flowmeter. The flow-rate of the right pulmonary artery, left
      pulmonary artery, superior vena cava and inferior vena cava were measured
      echocardiographically. The fluid energy loss was calculated. RESULTS: The
      postoperative right atrium pressure in group I was lower than in group III (P <
      0.05). The postoperative stroke index in group I and group II was higher than in
      group III (P < 0.01). The fluid energy loss was decreased when 50% or 25% right
      ventricle chamber was used (P < 0.01) and the fluid energy less in group II was
      less than in group III. CONCLUSIONS: Our experience suggested that atrio
      ventricular connection and total cavo-pulmonary connection would be better than
      atrio-pulmonary anastomosis for modified Fontan repair of tricuspid valve
      atresia.

PMID- 11832036
TI  - [Chemical-induced polycyst with renal tumor and expression of 8-OHdG in kidney
      tissue].
AB  - OBJECTIVE: To induce the rat model of polycyst with renal tumor and investigate
      the expression of 8-OHdG in the kidney tissues. METHODS: The rat model of
      polycyst with renal tumor, similar to human acquired cystic disease of the kidney
      (ACDK), was induced by oral administration of 2-amino-4, 5-diphenylthiazole (DPT)
      and N-nitrosomorpholine (NNM). Immunohistochemical method (LSAB) was used to
      assay the expression of 8-hydroxydeoxyguanosine (8-OHdG) in the rat kidney
      tissue. RESULTS: Three of 10 rats in the NNM group had renal solid adenomatous
      lesions. Bilateral polycysts were observed in all 9 rats of the DPT/NNM group.
      Seven of the 9 rats had cystic multistage renal tumor. In the DPT/NNM group, 4
      rats had cystic adenomatous lesions, but none in the other groups showed this
      lesion. In the model, adenomatous lesions derived from polycysts in the rats were
      closely consistent to human ACDK in morphology. The significant expression of 8
      OHdG was found on renal tubular cell, cystic epithelial cell, stromal cell and
      tumor cell in all rats of the NNM and DPT/NNM group. CONCLUSION: A rat model of
      polycysts with renal tumor, similar to human ACDK, induced by DPT and NNM
      provides evidences for further study on pathogenic mechanism in human ACDK with
      renal cell carcinoma. The expression of 8-OHdG, a DNA damage marker, in the renal
      tissues of rat model might help to explain the mechanism of cysticogenesis and
      carcinogenesis in human ACDK.

PMID- 11832037
TI  - Lung autotransplantation technique for treating central lung cancer of upper
      lobe.
AB  - OBJECTIVE: To assess the feasibility of applying lung autotransplantation
      technique in the treatment of central lung cancer of the upper lobe. METHODS: Two
      patients underwent double-sleeve right upper and middle bilobectomy. Because the
      length of resected bronchus or pulmonary artery involved by tumor was too long to
      perform tension-free anastomosis, we had to transplant the lower lobar vein into
      the proximal stump of the upper lobar vein. Another two patients underwent
      pneumonectomy firstly, because we could not perform sleeve lobectomy in suit as
      the tumor extended through the oblique fissure to the margin of the lower lobe.
      Subsequently, we resected the tumor parts at a separate table, and replanted the
      preservable part of the lung into the chest. RESULTS: Being followed up to
      December 1999, the patient 1, 3 and 4 had been alive with tumor free for 31, 18
      and 13 months. The patient 1 and 3 had a good living quality but the patient 4
      had a very poor activity. The patient 4 received resection of the replanted lung
      for pulmonary artery bronchus pleural fistula on the 42nd day after operation.
      The second patient died of tension pneumothorax associated with bronchopleural
      fistula on the 19th day after operation. CONCLUSION: Lung autotransplantation is
      an alternative technique for pulmonary preservation in patients with stage III
      central lung cancer of the upper lobe whose cardiopulmonary function is too poor
      to undergo pneumonectomy.

PMID- 11832038
TI  - [Arthroscopically assisted anterior cruciate ligament reconstruction using
      patellar tendon autograft fixed with interference screw].
AB  - OBJECTIVES: To evaluate the optimal position of bony tunnel, the firmness of
      tendon graft fixation and the effectiveness of postoperative function recovery in
      an arthroscopic approach for the minimally invasive reconstruction of anterior
      cruciate ligament (ACL). METHODS: In a single arthroscopic approach, the ACL was
      reconstructed by the bone-tendon-bone compound patellar tendon autograft with the
      fixation of an interference screw. RESULTS: ACL reconstruction was performed in
      49 patients, of whom 20 were followed up for over one year (average 1 year and 5
      months). Among the 20 patients, 13 were rated as excellent, 5 good, and 2 fair.
      The excellent and good rate went up to 90%. Reconstructed ACLs were reevaluated
      arthroscopically in 9 patients, in whom, 6 had good remodeling of ACLs.
      CONCLUSIONS: Our results indicated that this method has the advantages of less
      injury, optimal positioning of bone tunnel, firm graft fixation, and early
      rehabilitation. Compound bone-tendon-bone autograft allows firm fixation and
      biologic healing with good shape and tension remodeling.

PMID- 11832039
TI  - [Clinical analysis of 13 infected total knee replacements].
AB  - OBJECTIVE: To investigate the cause, treatment and its result of infected total
      knee replacements (TKRs). METHODS: Between 1987 and 1999, 13 infected TKRs in 13
      patients were treated with surgical debridement and one-stage or two-stage
      reimplantation. The preoperative average ROM of knees was 55 degrees and the
      average Hospital for Special Surgery (HSS) knee score was 36.5 points. Clinical
      results were evaluated after average follow-up for 3 years and 5 months. We
      analyzed the factors for TKR infection. RESULTS: No recurrent infection was
      noted, and pain was significantly alleviated in all patients. The average ROM of
      knees was 85 degrees and the average HSS knee score was 73.5 points. CONCLUSIONS:
      The high risk factors for TKR infection are rheumatoid arthritis, steroid
      administration, associated diabetes mellitus, hinged prosthesis and previous knee
      surgery. Early surgical debridement with intravenous antibiotics is necessary as
      soon as deep infection is detected. Two-stage reimplantation is more effective in
      eradicating deep infection than single debridement or one-stage reimplantation.

PMID- 11832040
TI  - [Risk factors for nosocomial infections after total knee replacement].
AB  - OBJECTIVE: To investigate prevalence and risk factors of nosocomial infections in
      patients with total knee replacement. METHODS: From August 1993 to October 1998,
      total knee replacement was performed on 363 patients (503 knees). The difference
      of nosocomial infection rates was statistically analyzed in comparison with
      different age, primary disease, and associated disease groups. RESULTS: No
      statistically significant difference was observed in nosocomial infection when
      compared rheumatoid arthritis with osteoarthritis, bilateral total knee
      replacement (TKR) with unilateral TKR and different ages. However, the higher
      nosocomial infection rate was related to the following factors: revision surgery,
      steroid administration and diabetes urinary infection. 28 female patients
      demonstrated higher urinary infection rate than that in other systems.
      CONCLUSIONS: Nosocomial infection rate of TKR in rheumatoid cases is related to
      steroid administration, accompanying diabetes mellitus, previous knee surgery,
      aged women and retention of urinary catheter. It is feasible to prevent
      nosocomial infection by controlling the above-mentioned risk factors.

PMID- 11832041
TI  - [Normal anatomy and related pathological changes of shoulder on MRI].
AB  - OBJECTIVE: To describe the normal anatomy and common abnormal changes of rotator
      cuff impingement and tears and recurrent anterior instability of shoulder joint
      in MRI pictures. METHODS: MRI was compared in 285 patients with shoulder diseases
      and 20 patients with symptomatic shoulder diseases. RESULTS: On oblique coronal
      image, the supraspinatus presented moderate signal intensity and low signal
      intensity in its tendon-muscle conjunction ranging from the humeral head to the
      greater tuberosity. The MRI manifestations of impingement lesion of the rotator
      cuff were as follows: high signal intensity of tendons, changes of their shapes,
      retraction of tendon-muscle conjunction, and muscle atrophy with high signal
      intensity. On T1-weighted axial image, the anterior and posterior glenohumeral
      labrum, the long head biceps tendon were displayed in low signal intensity. The
      anterior labrum manifested a sharp triangle contour and the posterior labrum a
      round one. The whole four muscles of the rotator cuff manifested on oblique
      sagital image. However, it was of less value in detecting the abnormalities of
      the rotator cuff and the glenohumeral labrum on sagittal imaging. The sensitivity
      in demonstrating rotator cuff complete tear was 95% for MRI and 91% for
      arthrography; the specificity was 88% for MRI and 100% for arthrography. The
      sensitivity and specificity of MRI were 96% and 75% for detecting glenoid labrum
      abnormalities, and 78% and 88% for detecting labrum tear in anterior recurrent
      dislocation of the shoulder. CONCLUSIONS: Magnetic resonance imaging with its
      excellent contrast resolution in multiple anatomic planes allows noninvasive
      visualization of bone and soft tissues in the rotator cuff and labrum.

PMID- 11832042
TI  - [Diagnostic value of arthrography and MRI in rotator cuff tears].
AB  - OBJECTIVE: To prospectively compare arthrography with MRI to determine the
      sensitivity and specificity in detecting rotator cuff tear. METHODS: 53 shoulders
      were studied. All patients underwent both arthrography and MRI. The results were
      compared with the findings of arthroscopy or open surgery. RESULTS: The
      sensitivity in demonstrating partial-thickness tears was 70% for arthrography and
      80% for MRI; the specificity was 75% for arthrography or MRI. The sensitivity in
      detecting full-thickness tears was 87% for arthrography and 90% for MRI, and the
      specificity was 100% for arthrography and 75% for MRI. CONCLUSION: The
      sensitivity of arthrography and MRI in detecting rotator cuff tears was
      identical. The specificity of arthrography in detecting full-thickness tears was
      higher that of MRI.

PMID- 11832043
TI  - [Control genes of chondrocyte apoptosis in osteoarthritic articular cartilage].
AB  - OBJECTIVE: To investigate the expression of bax and bcl-2 in normal human
      articular chondrocytes and in osteoarthritic articular cartilage. METHODS: The
      samples of articular cartilage were obtained from 9 patients and 6 normal
      subjects. Bax and bcl-2 mRNA were detected by reverse transcriptase/polymerase
      chain reaction (RT-PCR) and their expression proteins were analyzed
      immunohistochemically. TUNEL technique was used to study apoptosis in situ.
      RESULTS: Bax and bcl-2 mRNA was detectable in chondrocytes of both osteoarthritic
      and normal cartilage. Bax mRNA of chondrocytes from patients with osteoarthritis
      (OA) was overexpressed compared with the normal controls (P < 0.01), and OA
      cartilage chondrocyte also expressed more bcl-2 mRNA than the controls (P <
      0.05). There was no statistically significant difference of bax/bcl-2 between the
      two groups. Immunohistochemical staining demonstrated the same level of bax and
      bcl-2 proteins as their mRNA. A greater proportion of apoptotic chondrocytes were
      found in the OA cartilage than that in normal controls (4% - 14% versus 0 - 2%).
      CONCLUSIONS: Our results suggested that chondrocyte apoptosis was co-regulated by
      both bax and bcl-2. The ratio of bax to bcl-2 may contribute not only to the
      lower percentage of apoptotic chondrocytes, but also to the chronic pathologic
      process in OA.

PMID- 11832044
TI  - [Tissue engineered neo-cartilage using polymer substrates and chondrocytes:
      experimental study].
AB  - OBJECTIVE: To investigate the possibility of using poly beta-hydroxybutyrate
      (PHB) as a scaffold for chondrocytes and the feasibility of generating tissue
      engineered cartilage in rabbit animal model. METHODS: The articular cartilage
      from 4-week-old rabbits was enzymatically dissolved by type II collagenase, and
      chondrocytes were harvested and seeded into foams of PHB. After incubation for 1
      week in vitro, chondrocyte-polymer constructs were implanted subcutaneously into
      rabbits. Two respective control groups were established by subcutaneous
      implantation of PHB foams and chondrocytes alone. The rabbits were killed at 4,
      8, 12 weeks postoperatively, and the specimens were dissected and examined
      macroscopically, histologically and immunohistochemically. RESULTS: Specimens
      harvested from chondrocyte-polymer constructs and subjected to gross morphologic
      and histologic analysis demonstrated new cartilage formation, and those from
      control groups showed no cartilage formation. CONCLUSION: These findings
      demonstrate that the foam of PHB is not only a good "matrix" for cartilage tissue
      engineering, but also optimal scalffold for the seeding of chondrocytes to
      generate new cartilage that would be useful in plastic and reconstructive
      surgery.

PMID- 11832045
TI  - [Ultrasonically guided radio-frequency ablation of liver tumors with a clustered
      electrode: a report of 100 cases].
AB  - OBJECTIVE: To evaluate the efficacy of ultrasonically guided radio-frequency (RF)
      thermal ablation of liver tumors with a clustered electrode. METHODS: Clinical
      records of 100 consecutive patients who underwent RF tissue ablation 120 times
      were analysed. Image data, tumor size, clinic manifestation, and AFP value before
      and after the procedure were compared. RESULTS: A hundred cases at 10 days,
      thirty at 30 days, ten at 60 days after the procedure were subjected to color
      ultrasonography and CT scans, respectively. The tumor size decreased by 20% at 10
      days in 70% patients, decreased by 30% at 30 days in 80% patients, decreased by
      50% at 60 days in 3 patients. AFP value decreased in 50% of patients, no
      operative death was noted, and the rate of operative complication was 23% after
      ablation. CONCLUSION: Ultrasound guided RF thermal ablation of hepatic tumors is
      safe, applicable and effective.

PMID- 11832046
TI  - [Fiberoptic ductoscopy for patients with intraductal papillary lesions].
AB  - OBJECTIVE: To investigate the clinical significance of fiberoptic ductoscopy in
      patients with intraductal papillary lesions. METHODS: Fiberoptic ductoscopy was
      applied to patients with nipple discharge. The characteristics of those with
      intraductal papillary lesion were analysed. RESULTS: 92 patients were found to
      have intraductal papillary lesions. 68 patients were revealed to have single
      papillomas and 21 multiple papilloma. Three patients were diagnosed with
      papillomatosis. A total of 114 lesions were observed. 29.8% of these lesions were
      located in the segmental duct. 43.9% lesions were located in the first branch of
      the segmental duct and 17.5% in the second branch. Only 7.9% and 0.9% lesions
      were located in the third and the fourth branch. The average distance from
      lacteous pore to papillary lesion was 2.7 cm. Fiberoptic ductoscopy did not find
      lesions in 5 patients. CONCLUSIONS: Fiberoptic ductoscopy can be used to diagnose
      and locate intraductal papillary lesions. It is an effective diagnostic method
      for nipple discharge.

PMID- 11832047
TI  - Expression of alpha1 adrenoceptor subtypes mRNA in hepatic tissues of cirrhotic
      patients with portal hypertension.
AB  - OBJECTIVE: To investigate the expression of mRNA of alpha(1) adrenoceptor in the
      hepatic tissues of cirrhotic patients with portal hypertension. METHODS: Semi
      quantitative reverse transcription and polymerase chain reaction (RT-PCR) was
      used in 12 hepatitis virus B-related cirrhotic patients with portal hypertension
      and 15 controls who had no history of portal hypertension. In these patients,
      routine liver biopsy was performed. Special alpha(1) adrenoceptor subtype product
      and internal standard GAPDH product were both amplified by RT-PCR. The ratio of
      their integral optical density (IOD) was calculated as the relative expression of
      the alpha(1) adrenoceptor subtypes. RESULTS: The relative mRNA expression of
      alpha(1a) adrenoceptor subtype in the hepatic tissues was significantly lower in
      the cirrhotic patients (0.26 +/- 0.12) than in the controls (0.86 +/- 0.38, P <
      0.01). The relative mRNA expression of alpha(1b) adrenoceptor subtype in the
      hepatic tissues was also significantly lower in the cirrhotic patients (0.03 +/-
      0.01) than in the controls (0.23 +/- 0.10, P < 0.01). Neither the cirrhotic
      patients nor the controls showed alpha(1d) adrenoceptor subtype in the hepatic
      tissues. The relative mRNA expression of alpha(1a) adrenoceptor subtype was
      significantly higher than that of alpha(1b) adrenoceptor subtype in the hepatic
      tissues of both cirrhotic patients and controls (P < 0.01). CONCLUSIONS: The
      alpha(1a) adrenoceptor mRNA expression predominates in both normal and cirrhotic
      hepatic tissues. The expression of alpha(1b) adrenoceptor is less marked and
      there is no expression of alpha(1d) adrenoceptor. The decreased expression of
      mRNA of alpha(1a) and alpha(1b) adrenoceptor may underlie the decrease of
      alpha(1) adrenoceptor proteins often seen in the hepatic tissues of cirrhotic
      patients, and may play an important role in the pathogenesis and maintenance of
      portal hypertension.

PMID- 11832048
TI  - [Long-term results of combined therapy for primary osteosarcoma in extremities].
AB  - OBJECTIVE: To evaluate the survival rates, functional outcome, and complications
      between the combined and non-combined treatment of primary osteosarcoma of the
      extremities. METHOD: From 1977 through 1992, 170 patients with high-graded,
      nonmetastatic osteosarcoma were treated. Their average age at diagnosis was 21
      years old (ranging from 6 to 52). Tumors were observed at distal femurs in 80
      patients (47%), proximal tibia in 51 (30%), proximal humors in 10 and other
      locations in 22. Combined therapy (en bloc resection of tumor with preoperative
      and postoperative neoadjuvant chemotherapy) was given 104 patients and non
      combined therapy (tumor resection only) to 66. Ninety-four patients underwent
      limb salvage surgery. In 76 patients who received amputations or disarticulations
      33 received chemotherapy. RESULTS: The 5-and 10-year-survival rates were 61% and
      53% in the combined therapy group and 28% and 26% in the non-combined therapy
      group. Local recurrence rate was 23% in limb salvage surgery group and 5.2% in
      amputation group. Functional evaluation of 80 patients showed that the patients
      who underwent salvage surgery had higher functional scores than those who had an
      amputation according to MSTS scoring system (1993). The average scores reached
      71% in the salvage surgery group and 53% in the amputation group. CONCLUSIONS: In
      this study, long-term that combined therapy raised the survival rate of the
      patients with osteosarcoma. The ase of en bloc resection of bone tumor and
      reconstructive technique, has enable limb salvage procedures possible to produce
      excellent functional outcomes. The patients who well have responses to
      preoperative chemotherapy may have a higher survival rate.

PMID- 11832049
TI  - [Complications of massive allografts after segmental resection of malignant bone
      tumors].
AB  - OBJECTIVE: To analyze the postoperative complications of bone and joint
      allografting for the reconstruction of massive bone defect after the resection of
      malignant bone tumors and its management. METHODS: Bone-joint allografting for
      the reconstruction of massive bone defect after the resection of malignant bone
      tumors with different internal fixations was performed in 106 patients with
      complete follow-up data. Bone healing time, complication rate, and final results
      in different allografts were compared. Operation indications, complications and
      internal fixation were also analyzed. The final results were determined according
      to the Mankin's standard. RESULTS: Allografts Alcohol immersed were more
      susceptible to infection, non-union, etc. Allografts and combined prosthesis were
      superior to semi-articular transplantation. Complications included deep infection
      (10%), skin necrosis (12.2%), local recurrence (14.4%), and delayed union or non
      union (15.6%). Dynamic interlocked intramedullary nailing was superior to
      conventional intramedullar nailing and compression plates. CONCLUSIONS:
      Allografting is acceptable for the reconstruction of massive bone defect after
      tumor resection. Its results are encouraging after proper management of
      complications caused by surgical technique, internal fixation and soft tissue
      repair.

PMID- 11832050
TI  - [Relations of chemotherapy-induced tumor necrosis to plasma platin concentration
      and primary tumor temperature in patients with osteosarcoma in the lower
      extremities treated by hyperthermic isolation limb perfusion with cisplatin].
AB  - OBJECTIVES: To study the relations of chemotherapy-induced tumor necrosis to
      plasma concentration of platin and primary tumor temperature in hyperthermic
      isolation limb perfusion (HILP) with cisplatin, and to investigate the
      correlation between the tumor necrosis rate and the relapse-free survival (RFS).
      METHODS: Fifteen patients with II B osteosarcoma in the lower extremities were
      treated with neoadjuvant chemotherapy. Among them, 10 were male and 5 female. The
      average age was 18 years (ranging from 13 to 29). Chemotherapy included a single
      bonus dose of HILP with cisplatin (CDDP, 15 mg/m(2)). The plasma concentration of
      platin and the tumor temperature in the affected limb were measured during the
      course of the HILP with CDDP. Limb salvage surgery was performed in 9 patients
      and amputation in 6. After surgery, serial sections of the excised tumor
      specimens were made to determine the tumor necrosis rate. All of the patients
      were followed up for more than 5 years. RESULTS: The highest attained tumor
      temperature was between 41.4 degrees C - 43.0 degrees C (mean 42.3 degrees C +/-
      0.46 degrees C), and the platin concentration ranged from 4.56 microg/mL to 14.66
      microg/mL (mean 8.93 microg/mL +/- 3.16 microg/mL) during the course of HILP with
      CDDP. Thirteen patients with a necrosis rate of over 90% were well responded, and
      the remaining two with a necrosis rate 87.2% and 86.3% were poor responded. Eight
      patients remained tumor-free for 5 years. Primary tumor temperature and platin
      concentration were significantly related to the tumor necrosis rate (P = 0.001
      and P < 0.001, respectively). No significant correlation was noted between the
      long-term survival rate and the three parameters in the regression analysis.
      CONCLUSIONS: HILP with CDDP is useful in the treatment of primary osteosarcoma.
      Increased tumor necrosis ensure a successful surgical excision of tumor. HILP
      however is still limited to the patients who are not candidates for lime salvage
      surgery, because the same condition of high temperature and high concentration of
      platin are not applicable to distant metastasis.

PMID- 11832051
TI  - [Molecular cytogenetics of bone tumors].
AB  - OBJECTIVE: To study alterations of molecular cytogenetics of bone tumor serially.
      METHODS: Chromosomal analysis, immunohistochemistry, molecular hybridization,
      nested-PCR/SSCP, DNA sequence analysis, and gene transfection techniques were
      used to investigate the common bone tumors. RESULTS: Chromosomal aberrations were
      found in 50 cases of aggressive bone tumors, with a chromosome number aberration
      rate of 86.96% and a structure aberration rate of 93.94%. However, there were
      differences among different kinds of bone tumors. The incidence of chromosomal
      instability in 53 patients with bone tumors was higher than that in normal
      controls. Meanwhile, the fragile sites of chromosomes of the patients were
      closely correlated with the high nonrandom chromosome breakpoints of tumor cells
      and related oncogene loci. The data on p53 and Rb from 305 cases and 89 cases,
      respectively, indicated that abnormalities of p53 and Rb were common events in
      bone tumors. The accumulation of p53 protein and loss of Rb protein were more
      common in aggressive bone tumors. Structures and their products of related proto
      oncogenes (ras, myc, fos, bcl-2, met) were studied in 124 cases. Bone tumors
      presented multi-oncogenes abnormalities with differences in different
      pathological kinds. Exogenous wild-type p53 gene transfected into osteosarcoma
      cell line induced growth inhibition and apoptosis of tumor cells. CONCLUSIONS:
      Abnormalities of chromosomes, proto-oncogenes, and tumor suppressor genes
      frequently exist in bone tumor cells and are correlated with oncogenesis.

PMID- 11832052
TI  - [Expression and significance of AR in osteosarcoma].
AB  - OBJECTIVES: To determine the relationship between AR and pathological
      characteristics of osteosarcoma and to investigate the potential role of AR in
      the pathogenesis of osteosarcoma. METHODS: AR in the samples of the paraffin
      embedded tissues from 65 cases of osteosarcoma was immunohistochemically detected
      by streptavidin/peroxidase (SP) method. The pathology of osteosarcoma was
      classified and graded according to Liu Zijun's Classification. RESULTS: The
      positive rate of AR was 50.8% (33/65). The positive particles were distributed in
      the cytoplasm and nucleus. The positive rate of AR in osteosarcoma with higher
      grade of cell differentiation was lower than that in the tumor with lower one.
      There was no significant difference in different pathological type of
      osteosarcoma. CONCLUSION: AR exists in osteosarcoma and its positive rate is
      related to the cell differentiation of osteosarcoma.

PMID- 11832053
TI  - [Treatment of non iatrogenic injury of retrohepatic inferior vena cava].
AB  - OBJECTIVE: To study a repair method for injured retrohepatic inferior vena cava
      (IVC) associated with liver trauma. METHODS: Laceration of IVC was sutured
      bloodlessly after the injured retrohepatic IVC was occluded by compression
      combined with occlusion of the first hepatic hilus. RESULTS: From April 1996 to
      January 1999, the injured IVC was successfully repaired in 6 patients. The length
      of laceration was 2.9 cm (1.5 - 4 cm). The occlusion time was 9.2 min (6 - 15
      min) for the IVC and 20.5 min (15 - 29 min) for the first hepatic hilus,
      respectively. All patients recovered uneventfully, and the IVC was patency
      without stricture as showed by B-mode ultrasonography and CT. CONCLUSION: The
      injured retrohepatic IVC can be repaired by direct compression when the
      laceration of the IVC is caused by liver trauma.

PMID- 11832054
TI  - [Anomalous junction of pancreaticobiliary duct in congenital bile-duct cystic and
      cylindrical dilatation].
AB  - OBJECTIVE: To study the relationship between anomalous junction of
      pancreaticobiliary duct (APBD) and congenital bile-duct cystic as well as
      cylindrical dilatation. METHOD: Cholangiography was performed in 51 patients with
      bile-duct dilatation. RESULTS: APBD was diagnosed in 43 patients. In 8 patients
      (72%), the bile duct was drained into the pancreatic duct (B-P) in the cystic
      group, whereas in 14 patients (78%), the pancreatic duct was drained into the
      bile duct (P-B) in cylindrical group. There were significant differences in the
      internal diameter of the distal bile duct (P < 0.01), the maximal diameter of the
      pancreatic duct (P < 0.05) and the average angle of pancreaticobiliary junction
      (P < 0.01) in cystic and cylindrical groups. CONCLUSIONS: Different types of APBD
      after lead to different pathological changes of the biliary tract. The narrowed
      distal bile duct joins the pancreatic duct at a right angle in most cystic cases
      and the pancreatic duct joins the bile duct at an acute angle in most cylindrical
      cases.

PMID- 11832055
TI  - [Diagnosis and treatment of early colorectal cancer].
AB  - OBJECTIVES: To study the diagnostic methods of early colorectal neoplasm before
      operation and to evaluate the value of these methods for selection. METHODS:
      Fifteen patients with early colorectal neoplasms were examined pre-operatively by
      general colonoscopy to observe macroscopic appearance, by magnifying endoscopy to
      classify pit pattern type, and by endoscopic ultrasonography (EUS) to assess the
      penetrating depth of cancer invasion as well as regional lymph node metastases.
      According to these findings, diagnosis and clinical staging were made and proper
      treatment protocols were established. RESULTS: The diameter of the tumors ranged
      from 1 to 6 cm. Most lesions were subpedunculate type (8/15, 53%). Eight cases
      belonged to pit pattern type III L + V (8/15, 53%). EUS showed mucosal cancer in
      11 cases and submucosal cancer in 4. No lymph node metastasis was observed in any
      cases. Treatment methods included endoscopic polypectomy or endoscopic mucosa
      resection (EMR) in 6 cases, endo-surgery combined with open surgery in 2, and
      open surgery in 7. Pathological diagnosis showed mucosal carcinoma in 12 cases,
      submucosal carcinoma in 3. The accuracy of EUS was 93%. CONCLUSIONS: Magnifying
      endoscopy and EUS are useful for diagnosis of early colorectal cancer before
      operation, and correct preoperative staging of colorectal neoplasms is of
      significance in guiding treatment.

PMID- 11832056
TI  - [Adjustable interatrial communication in management of severe congenital heart
      disease].
AB  - OBJECTIVE: To assess the use of adjustable interatrial communication in patient
      with severe congenital heart disease undergoing open heart surgery. METHODS: From
      February 1998 to June 1999, 13 patients with severe and complex congenital heart
      disease underwent open heart surgery. Seven patients underwent total
      cavopulmonary connection, five patients repair of Ebstein's anomaly, and one
      patient right atrial-pulmonary connection. Adjustable interatrial communication
      was made in all patients. Four patients had the communication closed at the time
      of operation, 4 patients had the communication opened at the time of operation,
      and 5 patients had the communication adjusted and closed postoperatively.
      RESULTS: All patients had a smooth postoperative process. There were no
      postoperative death and no severe postoperative complications. CONCLUSION:
      Adjustable interatrial communication for the patients undergoing modified Fontan
      procedure or correction of Ebstein's anomaly may be advantageous.

PMID- 11832057
TI  - [Penetrating wounds of the heart: analysis of 56 patients].
AB  - OBJECTIVE: To assess the management of penetrating cardiac injuries. METHODS: 56
      patients with penetrating wounds of the heart were studied retrospectively. The
      study lasted for 11 years. RESULTS: Stab wounds accounted for 89.3% of the 56
      patients. 56 patients underwent thoracotomy. Preoperative infusion was less than
      1,000 ml in 68% of the patients. Preoperative pericardiocentesis was done only in
      2 patients, of whom one was false negative. Four patients with cardiac arrest
      soon after arrival were subjected to emergency thoracotomy; three survived. After
      the operation, 2 patients died of associated abdominal injuries and failure of
      cerebral resuscitation. The overall survival rate was 96.4%. CONCLUSIONS: Early
      diagnosis and prompt thoracotomy are essential to the treatment of penetrating
      cardiac injuries. Preoperative massive transfusion and pericardiocentesis are not
      advocated.

PMID- 11832058
TI  - [Microsurgical treatment of large or giant aneurysms in anterior circle of
      Willis].
AB  - OBJECTIVE: To improve the operative results in large or giant aneurysms of the
      anterior circle Willis. METHODS: Retrospective analysis was performed on 28
      patients with large or giant aneurysms of the anterior circle Willis after
      operation. Three-D CT angiography was used to detect and delineate aneurysm
      preoperatively. Improved operative technique included cranial base approach,
      temporary artery occlusion, intra-aneurysm decompression, obliteration of
      aneurysm with multiple clips, stepwise coagulation clipping and resection of
      aneurysms. RESULTS: Good results were noted in 24 patients (85.7%), fair in 2,
      and poor in 1. One patient died, but no patient with Hunt and Hess 0-III grade
      died. CONCLUSIONS: Three-D CT angiography is useful in delineating the shape,
      size, neck of aneurysms, and their relation to near arteries and to cranial base
      structures. These are helpful to improve operative results of large or giant
      aneurysms of the anterior circle of Willis.

PMID- 11832060
TI  - [Predictive factors for successful sperm recovery in azoospermia patients].
AB  - OBJECTIVE: To find any predictive factors for successful testicular sperm
      recovery in azoospermic patients. METHODS: 50 cases of azoospermia were subjected
      to testicular biopsy. Serum follicle stimulating hormone (FSH), concentration,
      testicular volume, testicular histopathology, and testicular sperm extraction
      (TESE) were determined in each cases. RESULTS: Neither serum FSH values nor
      testicular volume were predictive of spermatozoa in TESE. Testicular
      histopathology was specific for predicting successful sperm recovery (sensitivity
      96%; specificity 100%; accuracy 100%). CONCLUSIONS: Azoospermia patients with
      high FSH and small testis should be recommended for testicular biopsy and TESE to
      confirm if there is any testicular spermatozoa.

PMID- 11832059
TI  - [Craniovertebral decompression and posterior fossa reconstruction treatment of
      Chiari syringomyelia complex].
AB  - OBJECTIVE: To study the results of Chiari malformation/syringomyelia (CM-SM)
      complex treated by craniovertebral decompression and posterior fossa
      reconstruction (PFR). METHODS: 37 patients of CM-SM complex were treated
      surgically from 1994 to 1999. All patients underwent craniovertebral
      decompression and posterior fossa reconstruction. The procedure consisted of
      suboccipital craniectomy and laminectomy of C1 (when necessary C2), exploration
      and plugging of the obex, and resection of arachnoid adherence. A wide dural
      graft was used to reconstruct the cisterna magna artificially. Syrinx shunt was
      not performed. RESULTS: Follow-up for 0.5 to 4.5 years showed that 31 patients
      (83.8%) had their symptoms improved, 5 (13.5%) stabilized, but 1 (2.7%)
      deteriorated. Magnetic resonance was used to evaluate the morphological results.
      The shrinkage of the syrinx, upward migration of the hindbrain, the formation of
      an artificial cisterna magna were observed. CONCLUSIONS: Craniovertebral
      decompression and posterior fossa reconstruction in restoring the craniovertebral
      junction are recommended in the treatment of CM-SM complex.

PMID- 11832061
TI  - [Pathogenic microbes of biliary infection and their resistance to antibiotics].
AB  - OBJECTIVE: To understand the change of the main pathogenic microbes of biliary
      infection and their resistance rates to 12 antibiotics so as to instruct rational
      application of antibiotics clinically. METHODS: All isolates were identified by
      analytic products incorporation (API) bioMerieux. The susceptibility of
      antibiotics to 470 pathogenic microbes was tested by minimal inhibition
      concentration (MIC). RESULTS: There were 470 pathogenic microbes with positive
      biliary culture. The percentage of Escherichia coli, intestinal cocci and
      Klebsiella pneumoniae was 129 (27.4%), 82 (17.4%) and 76 (16.2%), respectively.
      In the resistance rates of the gram negative bacilli to 12 antibiotics, the
      lowest was 4.0% for imipenem followed by. 14.1% Ceftazidime and 16.9% amikacin.
      In the resistant rates of the gram positive cocci to 12 antibiotics, and had the
      lowest rate was 6.0% for vancomycin and 16.4% for imipenem. CONCLUSIONS: The main
      pathogenic microbes of biliary infection were Escherichia coli, intestinal cocci
      and Klebsiella pneumoniae. Imipenem is the first used for biliary infection in
      dealing with multiresistant intestinal cocci.

PMID- 11832062
TI  - [Troponin T during cardiopulmonary bypass].
AB  - OBJECTIVE: To evaluate the effect of cardiopulmonary bypass (CPB) on myocardial
      troponin T and its clinical significance and relationship to myocardial cell
      injury. METHODS: Thirty-seven patients underwent open heart surgery under CPB.
      The procedures included correction of congenital heart disease in 15 patients,
      valve replacement in 15, and coronary artery bypass grafting in 7. Blood samples
      were taken at four different time intervals for assessing a troponin T.
      Correlative factors including duration of clamping of aorta, dosage of
      cardioplegic solution, and metabolic acidosis were studied. RESULTS: When
      clamping time > 60 minutes, dosage of cardioplegia solution < 10 ml/kg and
      existing metabolic acidosis, the level of troponin T was significantly increased
      (P < 0.01). CONCLUSION: The elevation of troponin T is closely related to
      cardiopulmonary bypass, especially the duration of clamping of aorta,
      insufficiency of cardioplegia, and metabolic acidosis.

PMID- 11832063
TI  - [Genetic polymorphisms of Rb and susceptibility of esophageal cancer].
AB  - OBJECTIVE: To assess the possible association between the polymorphisms of Rb
      (intron 20, 17) and susceptibility of esophageal cancer so as to provide clues
      for genetic markers of esophageal cancer. METHODS: Samples were taken from 56
      normal Han people of Shaanxi, 47 esophageal cancer samples, and 31 peri-cancerous
      non-tumor. DNAs were analysed by using PCR technique. RESULTS: Ten alleles
      fragments were found in Han population of Shannxi by using primer Rb gene (intron
      20). PIC was 0.86. Heterozygosity was 0.7. In esophageal cancer tissues, PIC was
      0.82. Heterozygosity was 0.55. In peri-cancerous non-tumor, PIC was 0.87.
      Heterozygosity was 0.74. Distribution of genotype frequency was significantly
      different between Han population of Shaanxi and esophageal cancer (P < 0.01). Two
      alleles (945 bp, 630 bp + 315 bp) fragments were found in Han population of
      Shaanxi by using primer Rb gene (intron 17). Genotype frequency of Han population
      of Shaanxi was A/A: 0.28, A/B: 0.52, B/B: 0.20. Genotype frequency of esophageal
      cancer was A/A: 0.11, A/B: 0.77, B/B: 0.12. Distribution of genotype frequency
      was significantly different between Han population of Shaanxi and esophageal
      cancer (P < 0.05). Mutation of Rb gene was found in 7 cases. CONCLUSIONS:
      Polymorphism of Rb (intron 20) VNTR and Rb (intron 17) could be used as valuable
      markers. There should bea relationship between polymorphism of Rb VNTR and
      esophageal cancer susceptibility.

PMID- 11832065
TI  - [Mutation and expression of nm23-H1 and CD44 gene in prostate cancers].
AB  - OBJECTIVE: To study the role of nm23-H1 and CD44 gene in carcinogenesis and
      metastasis of prostate cancers. METHODS: Expression of nm23-H1/NDPK and CD44
      protein were analyzed in 32 cases of prostate cancers (Pca) and 12 control of
      benign prostate hyperplasia (BPH) paraffin embedded tissue by
      immunohistochemistry. Mutation and expression of their genes were detected by
      silver SSCP method, semiquantitative RT-PCR, and southern blot hybridization
      analysis respectively in 25 cases of fresh Pca and 15 control BPH tissue.
      RESULTS: nm23-H1 gene point mutation was detected in 13.3% (2/15) of Pca.
      Compared with the control tissue, the expression of nm23-H1 gene was increased
      significantly on both mRNA and protein levels in the carcinoma tissue (P < 0.05).
      The expression of nm23-H1 protein was also increased significantly in Pca with
      metastasis. The expression of CD44 standard form (CD44s) protein was
      significantly reduced in most Pca compared with BPH tissue. CD44s mRNA was
      detected in all Pca and BPH tissue, whereas CD44 variant (CD44v) without CD44v6
      was mainly detected in carcinoma tissue. CONCLUSIONS: The altered expression of
      CD44s and CD44v may co-regulate in the carcinogenesis and progression, whereas
      nm23-H1 gene may play a different role from CD44 in the progression of prostate
      cancer. CD44v6 may be a useful but not significant tool for detection of colon or
      bladder cancers.

PMID- 11832064
TI  - [Mechanism of abnormal scars with treatment of steroid].
AB  - OBJECTIVE: To investigate the mechanism of steroid in treatment of abnormal
      scars. METHODS: Apoptosis of different fibroblasts from 6 samples with keloid, 6
      samples with hypertrophic scar, and 6 samples of normal skin was observed under
      the condition of the media containing steroid in vitro. Proliferation,
      biosynthesis and apoptosis of fibroblasts of 6 samples of hypertrophic scars
      treated with intralesional injection of steroid were studied in vivo. RESULTS:
      Steroid could induce apoptosis of different fibroblasts in vitro in
      correspondence with increasing ratio of Bax/Bcl-2 proteins. Intralesional
      injection of steroid could inhibit proliferation of fibroblasts from hypertrophic
      scars by inhibiting PDGF-BB gene expression in vivo. Intralesional injection of
      steroid could inhibit procollagen gene expression to prohibit type I and III
      protein syntheses of fibroblasts from hypertrophic scars in vivo by inhibiting
      gene transcription. Intralesional injection of steroid could increase c-myc and
      p53 gene expression of hypertrophic scars in vivo, which induced apoptosis of
      cells. CONCLUSION: The effects of steroid on abnormal scars were achieved by
      inhibiting proliferation and biosyntheses of fibroblasts and promoting apoptosis
      of fibroblasts.

PMID- 11832066
TI  - [Apoptosis of endothelial cells in alteration of microvascular permeability in
      lung during sepsis].
AB  - OBJECTIVE: To investigate the apoptosis of endothelial cells in the alteration of
      microvascular permeability in lung during sepsis. METHODS: Twenty-four male NIH
      mice were subjected to cecal ligation and puncture (CLP) or sham operation (SO).
      The microvascular endothelial cells of the lungs were harvested at 3 hours and 12
      hours after operation. The apoptosis of endothelial cells (VIII factor related
      antigen positive cells) in the lungs was determined by 2-color flow cytometry
      (FITC-labeled VIII factor related antigen and PI) and Apop Tag) in situ apoptosis
      detection kit in situ. The apoptosis related gene (bcl-2) was detected by RT-PCR.
      The microvascular permeability in lung tissue was also examined. RESULTS: The
      apoptosis of microvascular endothelial cells was increased significantly at 12
      hours after CLP (5.03 +/- 0.92 vs. 3.48 +/- 1.21, P < 0.05). The increased
      apoptosis was paralleled with the decrease in bcl-2 gene expression. The
      microvascular permeability in lung tissue was slightly increased at 3 hours after
      CLP, but significantly increased at 12 hours after CLP (0.106 +/- 0.008 vs 0.047
      +/- 0.003, P < 0.01). CONCLUSIONS: Apoptosis in microvascular endothelial cells
      seems to be an important reason for the alteration of microvascular permeability.

PMID- 11832067
TI  - [Repairing peripheral nerve defects by tissue engineering techniques:an
      experimental study].
AB  - OBJECTIVE: To develop a novel effective substitute material or technique to
      repair peripheral nerve gap. METHODS: We inoculated expanded Schwann cells (SCs)
      at re-arranged bio-absorbable polymer polyglycolic acid (PGA) fiber and incubated
      for two weeks, then we developed a novel tissue-engineered scaffolds. The
      scaffolds were used as cellular isografts to bridge 15 mm long gap of sciatic
      nerve in inbred strains of Wistar rats. In an autologous and pure PGA fiber
      control group, the same surgical procedure was used. Evaluation included general
      observation, electromyographic examination, muscle measurement, and histological
      observation of serial sections at 12 weeks after surgery. The total number and
      density of reinnervation and thickness of myelin sheath was measured by
      computerized image analysis. RESULTS: SCs put out a long and thin prominence and
      migrated along the PGA fibers in spirality or parallel when they divided and
      finally rank into a cell-chain formation similar to Bungner's band. TEM/SEM and
      immunohistochemical survey demonstrated that the SCs at PGA fiber also secreted a
      great deal of ECMs included laminin, which play a very important role in
      peripheral nerve regeneration. Non-tubular scaffold comprised SCs and laminin
      (LN) channel in three-dimensional longitudinal rank. Animal transplantation study
      indicated the sensory and motor functional results of hindlimbs of experimental
      group rats reached to similar level of those found in nerve autograft control
      group. The number of reinnervation in the experimental group rats was slightly
      fewer than that in nerve autograft control group; but the axonal density was just
      reversal between the two groups because of a large area ischemic necrosis in the
      center of nerve autografts. CONCLUSION: This new paradigm offers a potential
      solution to repairing a long gap of peripheral nerve.

PMID- 11832068
TI  - Effect of extensive excision of burn wound with invasive infection on
      hypermetabolism in burn patients with sepsis.
AB  - OBJECTIVE: To evaluate the effect of extensive excision of invasive burn wound
      infection on hypermetabolic response in burn patients with sepsis. METHODS: Eight
      patients with major burn, complicated by invasive burn wound infection and
      sepsis, were consecutively admitted to our hospital from September 1997 to
      October 1998. Resting energy expenditures (REEs) were monitored by means of
      cardiorespiratory diagnostic system (Medical Graphics Corporation, USA) at
      patients' bedside. Plasma concentration of IL-6, IL-8, TNF-alpha, and LPS were
      assayed before and after surgical intervention and at the time when the patients'
      vital signs became stable. Correlation analysis between REEs and IL-6, IL-8, TNF
      alpha, and LPS were made, respectively. RESULTS: A total of 8 treated patients
      survived. Values of REE before surgical intervention were significantly higher
      than those after surgical intervention (P < 0.01), and when patients' vital signs
      became stable the values were significantly lower than those after surgical
      intervention (P < 0.01). The plasma concentrations of IL-6, IL-8, TNF-alpha, and
      LPS after excision of invasive burn wound infection were significantly lower than
      those before surgical intervention (P < 0.05). The lowest levels of these
      inflammatory mediators were observed when the conditions of patients became
      stable, and the values were significantly lower than those before surgical
      intervention (P < 0.001). There was a significant positive correlation between
      REE level and respective values of plasma IL-6, IL-8, TNF-alpha, and LPS (P <
      0.01). CONCLUSIONS: It seemed that the extensive excision of invasively infected
      burn wound in patients with major burn should be performed as early as possible
      to reduce an increased release of inflammatory mediators and to control the
      hypermetabolic response during sepsis.

PMID- 11832069
TI  - [Abdominal aortic aneurysm treated by endovascular stent-graft and conventional
      surgical repair: a comparison].
AB  - OBJECTIVE: To evaluate the feasibility of abdominal aortic aneurysm (AAA) treated
      by endovascular stent-graft. METHODS: The clinical data of 52 patients with AAA
      treated by endovascular stent-graft (n = 20) and conventional surgical repair (n
      = 32) were analysed retrospectively. Patients conditions, operative hours, blood
      loss, function recovery and complications were compared. RESULTS: No significant
      difference was observed in sex, age, other disease, anesthesia risk category,
      aneurysm type, aneurysm diameter, technical success rate, and mortality rate
      between the groups (P > 0.05). The patients who underwent intraluminal treatment
      had significant reductions in operative time, blood loss, intensive care unit and
      hospitalization. But there was a high complication rate in the endovascular stent
      graft group. All complications were connected with the interventional technique;
      endo-leak was the chief complication after operation. CONCLUSIONS: Endovascular
      treatment has marked merits such as reduced trauma, short hospitalization stays,
      and early functional recovery. It is suitable for the patients who can't undergo
      open surgical repair. But the complications caused by this technique needs
      further study.

PMID- 11832070
TI  - [Long-term effect on preoperative ulnaris arterial intubation chemotherapy in
      treatment of stage III breast cancer].
AB  - OBJECTIVE: To evaluate preoperative ulnaris arterial intubation chemotherapy as a
      step of multidisciplinary treatment of stage III breast cancer. METHODS: 109
      patients with stage III breast cancer were studied. 64 patients (group A) were
      treated by preoperative ulnaris arterial intubation chemotherapy and others
      (group B) were not. The 5 and 10-year survival rates and disease-free survival
      rates were analyzed. RESULTS: In patients with stage III breast cancer, the
      overall response rate of group A was 76.6%, and the response rate to histological
      study was 89.1%. The 5-year and 10-year survival rates of group A were 64.0% and
      47.9% respectively. The disease-free survival rate of group A was 59.4% at 5
      years and 43.3% at 10 years. All were higher than the 5-year and 10-year survival
      rates (31.1%, 21.9%) and the 5-year and 10-year disease-free survival rates
      (22.2%, 12.5%) of group B (P < 0.05). CONCLUSION: Preoperative ulnaris arterial
      intubation chemotherapy is an effective measure for the treatment of stage III
      breast cancer. It can improve the long-term effects on stage III breast cancer
      and reduce local relapse and distant metastasis.

PMID- 11832071
TI  - [Liver transplantation for hepatocellular carcinoma: a report of 8 patients].
AB  - OBJECTIVE: To evaluate the feasibility of liver transplantation as a treatment
      for hepatocellular carcinoma (HCC). METHODS: From July 1995 to October 1998,
      eight liver cancer patients with cirrhosis underwent liver transplantation in
      Queen Mary Hospital. The liver grafts were obtained from 6 brainstem dead donors
      and 2 living donors. Five patients had known HCC and 3 had incidental tumor
      identified in the explanted liver. TNM staging: stage II (5 cases), stage III (2
      cases) and stage IV a (1 case). After liver transplantation, the patients were
      followed up prospectively for a median of 36 months. Except for one patient who
      had preoperative chemotherapy, no anticancer treatment was given before and after
      transplantation. RESULTS: Three patients had acute rejection, 5 developed
      complication in early post transplantation. All were treated promptly and
      improved. One patient died one year after operation from septicemia. The
      recurrence-free survival rates of one and three years were 100% and 83.3%,
      respectively. CONCLUSIONS: Liver transplantation is a feasible method for
      treatment of HCC in selected patients. Living donor liver transplantation can
      overcome the problems of donor shortage and tumor growth while waiting for liver
      transplantation.

PMID- 11832072
TI  - [Fresh femoral shaft fractures treated with un-reamed intramedullary nail: 203
      cases].
AB  - OBJECTIVE: To discuss the experience treating fresh femoral shaft fractures with
      un-reamed intramedullary nail. METHODS: 203 cases of fresh femoral shaft
      fractures who had been treated with un-reamed intramedullary nail from November.
      1995 to January. 1999 were analyzed retrospectively. 18 cases were open,
      classified as Gustilo I, and. 185 cases were closed. Traction table and image
      intensifier were used during operation. Closed reduction, un-reamed and free hand
      distal locking technique were used. Active movements of nearby joints were
      encouraged and partial weight bearing of 10 - 15 kg were allowed right after
      operation. RESULTS: All 203 cases of fresh femoral shaft fractures got bone union
      within 4 - 6 months. No case of delayed union and infection happened. 1 distal
      locking screw was broken. All patients gained normal extremity functions.
      CONCLUSION: Un-reamed intramedullary nailing of fresh femoral shaft fracture has
      less damage to the local soft tissue and blood supply. It has a relative stable
      fracture fixation, and less interruption to the healing procedure. It is one of
      the best methods for treating femoral fracture.

PMID- 11832073
TI  - [Simultaneous pallidotomy and thalamotomy for Parkinson's disease with
      intractable tremor].
AB  - OBJECTIVE: To evaluate the clinical necessity, outcomes, safety, and indications
      of contemporary combined pallidotomy and thalamotomy for Parkinson's disease (PD)
      with intractable tremor. METHODS: The UPDRS data from 20 patients who received
      simultaneous pallidotomy and thalamotomy were analyzed retrospectively. During
      the same period, 326 patients were subjected to unilateral pallidotomy.
      Improvement and complications between the two groups were compared. RESULTS:
      Contemporary pallidotomy and thalamotomy effectively improved parkinsonian
      symptoms as did pallidotomy alone. This procedure completely abolished
      intractable tremor in all 20 patients. No permanent complications occurred.
      CONCLUSIONS: Contemporary combination of pallidotomy and thalamotomy is effective
      and safe in treating regular parkinsonian symptoms and intractable tremor.

PMID- 11832074
TI  - [CO2 laser-microscopy technique in treating tumors near the sella turcica].
AB  - OBJECTIVE: To assess the laser-microscopy technique in dealing with tumors near
      the sella turcica. METHODS: Sixteen patients with tumors near the sella turcica
      who had been treated surgically by laser-microscopy technique from October 1996
      to June 1998 in Haikou municipal hospital were analyzed retrospectively. RESULTS:
      In these patients, 11 patients had tumors bodies excised totally, and 5 had
      tumors bodies excised partially. All of then were followed up for 4 to 30 months.
      The curative effects were satisfactory. In 9 patients with defect in vision
      before operation, 6 showed obvious improvement, 2 moderate improvement, and 1
      unmarked improvement. In 6 patients with endocrinopathy before operation, 4
      returned to normal, and 2 showed improvement. In 4 patients with intracranial
      hypertension before operation, symptoms were retrieved. Only one patient who had
      diabetes insipidus after operation, and recovered after medication. CONCLUSIONS:
      CO(2) laser-microscopy technique the treatment of tumors near the sella turcica
      is advantageous: few accidental injuries because of its high-accuracy; less
      harassment to the hypophysis and subthalamus; less complication; small exposure
      of operative field; less bleeding and clear operative field; no stimulation of
      metastasis of carcinoma;and no interference of bioelectric current.

PMID- 11832075
TI  - [Microsurgical treatment of cranial base meningioma].
AB  - OBJECTIVE: To improve the total removal rate of cranial base meningiomas, and to
      reduce the mortality and morbidity. METHODS: 103 patients with cranial base
      meningiomas were treated by microsurgery. Tumors of different position were
      resected by variant transcranial base approaches and the operative methods.
      RESULTS: and complications were analyzed retrospectively. RESULTS: Total removal
      of Simpson's 1 to 2 grade was performed in 63 patients, subtotal removal in 31
      and partial removal in 9. Good postoperative recovery was noted in 75 patients,
      skull nerve paralysis in 24 and death 4. CONCLUSION: Using skull base
      microsurgery to resect cranial base meningiomas could shorten the distance of
      surgical approach and lessen the damage to brain.

PMID- 11832076
TI  - [T1, T2 squamous or adenocarcinoma of the lung:characteristics of lymph node
      metastasis and its clinical significance].
AB  - OBJECTIVES: To investigate the frequency, distribution and features of lymph node
      metastasis in T(1)/T(2) squamous or adenocarcinoma of the lung, and to provide
      evidence for extensive dissection of lymph nodes. METHODS: 254 patients with
      T(1)/T(2) squamous or adenocarcinoma of the lung underwent R2 surgery plus
      extensive dissection of hilar, interlobular and mediastinal lymph nodes according
      to the grouping system proposed by Naruke. RESULTS: 1 685 groups of lymph nodes
      were dissected. The metastatic rates of N(1) and N(2) was 20.0% and 10.2%
      respectively. Significant difference existed between T(1) and T(2) tumors (P <
      0.01). No N(2) metastasis was found in T(1) squamous cell carcinoma. N(2)
      metastatic rates were 22.0% in squamous cell carcinoma and 40.9% in
      adenocarcinoma (P < 0.01). 64.3% of squamous carcinoma spread to only one group
      of N(2) nodes, and over 3 groups of lymph nodes were positive in 46.2% of
      adenocarcinoma. Saltatory metastasis accounted for 57.5% of N(2) metastasis.
      13.6% of N(2)-positive tumors in upper lobes metastasized to the lower
      mediastinum, whereas 51.6% of N(2)-positive cancers in the lower lobes spread to
      the upper mediastinum. CONCLUSIONS: The frequency of lymph nodes metastasis
      increases with the growth of tumors. Metastasis in adenocarcinoma occurs more
      frequently than in squamous carcinoma. Tumor at any site can metastasize to the
      distant mediastinum. Except for T(1) squamous cancer, radical surgery can be
      achieved only by extensive dissection of ipsilateral intrapulmonary and
      mediastinal lymph nodes.

PMID- 11832078
TI  - [Xanthogranulomatous pyelonephritis].
AB  - OBJECTIVE: To study the diagnosis and treatment of xanthogranulomatous
      pyelonephritis (XGP). METHOD: The clinical characteristics, diagnosis and therapy
      of 28 cases of XGP were discussed. RESULTS: The clinical characteristics of XGP
      included: calculi or obstruction in urinary tract, and damage to kidney;
      complication of urinary tract infection; anemia, increased ESR and dysfunction of
      liver. 13 patients with XGP were diagnosed before operation. Nephrectomy was
      performed in 20 patients. Kidneys were preserved in 8 patients. All patients
      recovered after operation. CONCLUSIONS: The clinical characteristics and image of
      XGP are good to preoperative diagnosis. They are useful to differentiate XGP from
      renal carcinoma and other renal infectious disease. Surgery and antimicrobial are
      important to XGP. Nephrectomy might be done in patients of stage III kidney may
      be preserved in patients of stage I and stage II.

PMID- 11832077
TI  - [Prevention and treatment of MODS in severely burned patients: an institute based
      retrospective study].
AB  - OBJECTIVE: To determine if the preventive and treatment measures developed from
      basic and clinical research work have any effects on the incidence and outcome of
      MODS in severely burned patients. METHODS: 657 extensively burned patients (burn
      size exceeding 30% TBSA) admitted to the clinical department from January 1970
      through October 1999 were studied. The morbidity and mortality rates were
      compared in patient groups hospitalized before and after January 1990 when major
      preventive and treatment measures began to be extensively executed. These
      measures consisted of prompt, rapid and adequate fluid resuscitation, restoration
      of bowel blood supply with anisodamine (654 - 2), use of oxygen free radical
      scavengers (e.g. mannitol, vitamin C and E), extensive escharectomy during shock
      stage, early tube feeding, support of organ function, etc. RESULTS: Before 1990
      when very few preventive and treatment measures were applied, the incidence of
      MODS, 17.3% (64 out of 369), and the death rate 87.5% (56 out of 64). After 1990,
      with the application of various preventive measures and treatment, the morbidity
      and mortality rates were reduced to 6.9% (20/288) and 40.0% (8/20), respectively.
      CONCLUSION: Our results suggest that measures which mitigate or eliminate the
      predisposing and causative factors of MODS may be salutary in the prevention and
      treatment of MODS after extensive burn injury.

PMID- 11832079
TI  - [Multivariate analysis of prognostic factors in renal cell carcinoma].
AB  - OBJECTIVE: To assess the effect of prognostic factors on renal cell carcinoma
      (RCC). METHODS: 316 cases of RCC were reviewed retrospectively. Their survival
      rates were calculated by Kaplan-Meier method and statistical differences were
      determined by Log-rank test. Significant prognostic factors were evaluated by
      Cox's multivariate proportional hazard model. RESULTS: After 40.3 +/- 18.5 month
      follow-up, the overall 5-year survival rate was 62.3%. By multivariate analysis,
      nine factors were included in Cox's multivariate proportional hazard model. M was
      the most important prognostic factor in RCC (P = 0.0013), and the others in turn
      were T (P = 0.0182), age (P = 0.0347), performance status (P = 0.0423), N (P =
      0.0471), lymphadenectomy (P = 0.0542), grade (P = 0.0775), serum albumin (P =
      0.1536), and serum creatinine (P = 0.4543). CONCLUSIONS: The significant
      prognostic factors in RCC were T, N, and M. Age and performance status showed the
      effect on prognosis of RCC. Lymph-node dissection also revealed a meaningful
      effect on relative lower stage of RCC.

PMID- 11832080
TI  - [Transurethral electrovaporization-ablation of superficial bladder carcinoma].
AB  - OBJECTIVE: To observe short-term curative effect of transurethral
      electrovaporization-ablation of superficial bladder carcinoma. METHODS: 82 cases
      of superficial bladder carcinoma were treated using transurethral
      electrovaporization-ablation. RESULTS: The mean operative time was 36 min. One
      patient was complicated with extraperitoneal bladder perforation. No patients
      experienced TUR syndrome and severe hemorrhage. During the follow up for 2-18
      months, 3 patients had recurrence respectively at 7, 8 and 10 months after the
      operation. CONCLUSIONS: Cut-electrode had vaporization and ablation with smooth
      surface of the wound and speed. The advantage includes safety, few complication,
      evident efficacy, and short hospitalization.

PMID- 11832081
TI  - [Somatostatin and growth hormone promote spontaneous closure of enterocutaneous
      fistula].
AB  - OBJECTIVE: To find out the method for promoting spontaneous heal of
      enterocutaneous fistula. METHODS: Experimentally, we investigated the effect of
      rhGH on wound granulation and intestinal mucosa. Clinically, combined
      somatostatin and rhGH was compared with somatostatin in the treatment of enteric
      fistula. RESULTS: Animal studies demonstrated that rhGH was effective to increase
      the content of hydroxyproline and amount of fibroblast cell in wound granulation.
      In clinical trial, the spontaneous cure rate was significantly higher in patients
      treated with combined rhGH and somatostatin than in those treated with
      somatostatin alone (96.5% vs 68.4%, P < 0.01). CONCLUSION: Combined rhGH and
      somatostatin is a new therapeutic method for the treatment of enteric fistula. It
      may promote the spontaneous cure of enteric fistula.

PMID- 11832082
TI  - [The relationship of expression of CD44v6 with metastasis and prognosis in breast
      cancer].
AB  - OBJECTIVE: To study the relationship of expression of CD44v6 with metastasis and
      prognosis in breast cancer. METHODS: The expression of CD44v6 protein in 78
      paraffin and 37 fresh specimens of breast carcinomas was detected with
      immunohistochemistry (IHC). The expression of CD44v6 mRNA in 37 fresh specimens
      of breast carcinoma was detected with RT-PCR. The correlation of tumor size, TNM
      stage, status of axillary lymph node, tissue grade, prognosis and CD44v6
      expression in breast cancer was analyzed to compare the sensitivity of the two
      methods. RESULTS: The expression of CD44v6 in breast cancer was correlated to
      metastasis of the axillary lymph node, tumor size and TNM stage. It was an
      important factor affecting survival of patients with breast cancer. Positive
      expressive rates of CD44v6 protein and mRNA were 70.3% and 59.5% respectively in
      37 specimens of fresh carcinoma tissues (P > 0.05). CONCLUSIONS: The expression
      of CD44v6 is closely related to metastasis and prognosis in breast cancer, and
      the sensitivity to detect CD44v6 expression shows no significant difference
      between IHC and RT-PCR.

PMID- 11832084
TI  - [The growth inhibitory effects by transfection of p16 gene on human pancreatic
      cancer cell line].
AB  - OBJECTIVE: To elevate the growth inhibitory effects by transfection of p16 gene
      on human pancreatic cancer cell line JF305. METHODS: Recombinant eukaryotic
      expression vector pDOR-p16 containing exogenous human wt-p16 cDNA and vector
      containing neomycin resistance gene only were introduced by Liposomes-mediated
      gene transfection into JF305 cell line which did not express endogenous p16. By
      using PCR amplification, in situ hybridization, and immunocytochemistry, the
      clones obtained were detected for efficiency of transfection and effect of vector
      expression and observed for the changes of their biologic characteristics.
      RESULTS: Exogenous wt-p16 was successfully transferred into JF305 cells and
      obtained permanent expression. The growth rate of these transfected JF305 cells
      in regular medium and soft agar was inhibited. The percentage of phage G(1) cells
      increased and that of phage S cells decreased by analysing cell cycle. The
      ultrastructural changes of the cells observed under electron-microscope revealed
      growth retardation. CONCLUSION: p16 is a candidate for cancer gene replacement
      therapy of human pancreatic cancer.

PMID- 11832083
TI  - [The effects of the expression of VEGF and KDR on the angiogenesis, growth and
      metastasis of hepatocellular carcinoma].
AB  - OBJECTIVE: To investigate the effects of VEGF (vascular endothelial growth
      factor) and KDR (kinase insert domain containing receptor) on the angiogenesis,
      growth and metastasis of hepatocellular carcinoma. METHODS: With the methods of
      immunohistochemistry and in situ hybridization, specimens from 45 HCC
      (hepatocellular carcinoma) patients, 21 cirrhotics, 8 normal livers patients were
      stained. Image analysis was followed, and the relationship between VEGF, KDR
      expression and the pathological characteristics of HCC was studied. RESULTS: VEGF
      was highly expressed in HCC and was correlated with the angiogenesis of HCC. The
      expression rate and the intensity of VEGF were correlated with the metastasis and
      capsule formation of HCC. KDR was expressed not only in vascular endothelial
      cells, but also in some HCC cells. CONCLUSIONS: VEGF may play an important role
      in the angiogenesis, metastasis, and capsule formation. The KDR expression in HCC
      cells may be a behavior of autocrine.

PMID- 11832085
TI  - [Expression of T cell factor 4 in renal cell carcinoma].
AB  - OBJECTIVE: To investigate of the transduction of Wnt/Frizzled pathway in nuclei
      and the function of TCF4 (T Cell Factor) in renal cell carcinoma. METHODS: TCF4
      mRNA are tested through RT-PCR and Northern Blot in renal cancer tissue and renal
      cancer cell strain (GRC-I). RESULTS: It has been certificated that TCF4 are
      expressed in renal cell carcinoma, at the same time, there are some different
      splice of TCF4 in renal cancer. A new 300bp mutant gene are found. CONCLUSION:
      TCF4, an important molecular of Wnt/Frizzled pathway, takes part in the formation
      and progression of renal cell carcinoma, different splice of TCF4 is one of the
      mechanism.

PMID- 11832086
TI  - [The effect of pentoxifylline on endotoxin-induced biopterin formation in
      rabbits].
AB  - OBJECTIVE: To observe the potential effect of pentoxifylline on endotoxin
      mediated biopterin (tetrahydrobiopterin and more oxidized species) formation and
      systemic hemodynamics. METHODS: Rabbits were subjected to endotoxic shock induced
      by a bolus intravenous injection of E. coli O26B6 lipopolysaccharide (400
      microg/kg). 28 animals were divided into sham-operation group (n = 8), endotoxic
      shock group (n = 10), and pentoxifylline-treated group (n = 10). Plasma biopterin
      and tumor necrosis factor-alpha (TNF) levels, and guanosine triphosphate
      cyclohydrolase I (GTP-CHI) activity in tissues were determined at various
      intervals. RESULTS: Treatment with pentoxifylline significantly decreased plasma
      biopterin and TNF levels at 2 to 8 hours after endotoxin challenge (P < 0.05, P <
      0.01), and inhibited GTP-CHI activities in the liver, lung, and myocardial
      tissues (P < 0.05). Meanwhile, systemic hemodynamic parameters, including mean
      arterial pressure, cardiac output, and total peripheral resistance, in the
      treatment group were much higher than those in the endotoxic shock group.
      CONCLUSIONS: These data suggest that early treatment with pentoxifylline can
      effectively inhibit endotoxin-induced biopterin synthesis and release, and
      markedly improve systemic hemodynamics during septic shock.

PMID- 11832088
TI  - Right ventricular function of patients with septic shock: clinical significance.
AB  - OBJECTIVE: To understand the effect of right ventricular dysfunction on
      circulatory supportive therapy in patients with septic shock. METHODS: 25
      patients with septic shock who were admitted consecutively to the intensive care
      unit (ICU) of Peking Union Medical College Hospital were observed prospectively.
      Hemodynamic profile of the left side and right side heart was monitored with
      right ventricular ejection fraction catheter and transthoracic echocardiography.
      Intramucosal pH (pHi) and oxygen delivery were also monitored to illustrate any
      relation with patient outcome. RESULTS: Stroke volume index (SVI) and right
      ventricular ejection fraction (RVEF) were significantly higher in survivors than
      in nonsurvivors (P < 0.01 and < 0.05, respectively). The pulmonary vascular
      resistance index (PVRI) was significantly lower in survivors (P < 0.01). At the
      onset of shock, the left ventricular end-diastolic volume index (LVEDVI) of both
      groups was very low, and steadily increased in survivors but not in nonsurvivors.
      Left ventricular ejection fraction (LVEF) and systemic vascular resistance index
      (SVRI) decreased during treatment, which were not different in both groups. Right
      ventricular end-diastolic volume index (RVEDVI) increased in both survivors and
      nonsurvivors. Oxygen delivery of nonsurvivors was significantly lower than that
      of survivors. LVEDVI and RVEF were correlated with SVI in both survivors and
      nonsurvivors. CONCLUSIONS: The impairment of right heart function may be more
      severe than that of left heart function in the patients with early septic shock.
      "Right heart priority" must be seriously considered in supportive treatment of
      patients with septic shock. The present treatment of septic shock has significant
      limitations, and even aggravates the existing cardiac dysfunction.

PMID- 11832087
TI  - [The effects of platelet-derived growth factor-AA on the osteoclasts].
AB  - OBJECTIVE: To study the effects of platelet-derived growth factor (PDGF)-AA on
      the osteoclasts. METHODS: The PDGF receptor alpha (PDGFR-alpha) was detected on
      the osteoclastic membrane with immunoelectronmicroscopy. Acid phosphatase (ACP)
      and tartrate-resistant acid phosphatase (TRAP) activities were measured
      kinetically and the introcellular hydrogen ions were calculated on the confocal
      laser scanning microscope (CLSM) stained with SNAFL. Stained by toluidine blue,
      the area and number of the resorption pits were determined with the Leica
      Quantimet 500 system. RESULTS: The colloidal gold precipitated on the cellular
      membrane, and the TRAP activity had no difference (P > 0.05). Hydrogen ions rose
      significantly but their release could not be promoted by PDGF-AA. The changes of
      the resorption pits were not significant. CONCLUSIONS: The PDGF-AA could promote
      hydrogen ions yielding but not stimulate osteoclastic bone resorption due to the
      significant TRAP changes of TRAP activities.

PMID- 11832089
TI  - [Relationship between new TNM classification and the prognosis and biological
      behavior of gastric cancer].
AB  - OBJECTIVE: To determine the clinical value of 1997 TNM classification of gastric
      cancer. METHODS: 334 cases of gastric cancer with regional lymph node metastasis
      were used to determine the relationship between new TNM classification and the
      prognosis and biological behavior compared with old classification (1987).
      RESULTS: The 5-year survival rates of the old pN(1), pN(2) were 49.6% and 33.5%
      respectively; those of the new pN(1), pN(2), pN(3) were 48.5%, 24.1% and 5.6%
      respectively. There was a highly significant difference in survival in different
      new pN groups (P < 0.01). The new pN classification was correlated with the depth
      of cancer invasion, as well as the macroscopic type, growth pattern and serosal
      type (P < 0.01). Multivariate COX model analysis showed that the new pN
      classification was the most significant independent prognostic factor.
      CONCLUSIONS: The new TNM classification is not only an objective, simple and
      reproducible system, but also a significant prognostic index for gastric cancer
      superior to the old classification.

PMID- 11832090
TI  - [Total meso-rectal excision in low anterior resection with double stapling
      technique].
AB  - OBJECTIVE: To elucidate the value of total meso-rectal excision (TME) in low
      anterior resection with double stapling technique. METHODS: During January 1993
      to October 1998, 306 cases of rectal lesions were treated by total meso-rectal
      excision in low anterior resection (LAR) with double stapling technique. Among
      the patients with rectal cancer, 235 (78.86%) were treated by low anterior
      resection and 97 (41.28%) by ultra-low anterior resection. RESULTS: No operative
      death was noted, and anastomotic leakage occurred in 9 (2.94%) patients. Ureter
      injury occurred in 2 (0.65%) patients. 32 (10.46%) patients suffered from
      anastomotic stenosis, 31 mm diameter of stapler for 27 (12.68%) patients and 33
      mm diameter of stapler for 5 patients (5.38%). Local recurrence occurred in 20
      (6.71%) patients: Dukes'B 4 (2.33%) patients, Dukes'C 9 (12.5%) patients, and
      Dukes'D 7 (53.85%) patients. CONCLUSIONS: Total meso-rectal excision can
      effectively reduce the local recurrence rate after LAR with double stapling
      technique. Since the recurrence is closely related to the stage of the disease,
      early detection, early diagnosis and early treatment are extremely important.

PMID- 11832091
TI  - [Postoperative recurrence of T2 stage gastric cancer].
AB  - OBJECTIVE: To study the clinicopathological characteristics of T(2) gastric
      cancer and its postoperative recurrence. METHOD: 124 T(2) gastric cancer patients
      were divided into two groups: 42 patients with postoperative recurrence (Group 1)
      and 82 patients without recurrence (Group 2). RESULTS: The recurrence rate of
      local tumor was significantly lower in Group 1 (26.2%) than in Group 2 (45.1%).
      Deep invasion was highly different between the two groups. Circular muscle tumors
      were seen in Group 1 (4.8%) and in Group 2 (30.5%), whereas sub-serosa tumors
      were seen in Group 1 (61.8%) and in Group 2 (25.6%). The rate of lymph node
      metastasis was significantly higher in Group 1 (88.1%) than in Group 2 (57.3%).
      The mean number of positive nodes was (7.02 +/- 6.50) in Group 1 and (2.16 +/-
      2.04) in Group 2(P < 0.01). Local recurrence rate and distant metastasis rate in
      Group 1 were 54.8% and 46.2% respectively. The median survival was 26.5 months in
      Group 1 and 57.0 months in Group 2 (P < 0.01). The 1-, 3-, 5-year survival rate
      in Group 1 and Group 2 were 61.4% vs 97.6%, 18.7% vs 95.9%, and 8.3% vs 95.9%,
      respectively. CONCLUSION: Poor prognosis is seen in T(2) gastric cancer patients
      with postoperative recurrence. Extended gastrectomy and multi-therapy are
      necessary for the patients with the risk factors so as to decrease local
      recurrence.

PMID- 11832092
TI  - [Effects of selective preoperative intra-arterial infusion chemotherapy on
      apoptosis and proliferation of rectal cancer cells].
AB  - OBJECTIVES: To study the effects of anti-cancer drugs on apoptosis and
      proliferation of rectal cancer cells in vivo. METHODS: 114 patients with rectal
      cancer were treated by selective preoperative intra-arterial infusion
      chemotherapy. The rectal tumor tissues were derived before chemotherapy and 7 -
      12 days after this treatment. In the tissues, apoptotic cells were examined by
      TUNEL method, and the expression of PCNA was examined by S-P staining. RESULTS:
      Before chemotherapy, the mean AI of tumor cells was 5.81 per thousand before
      chemotherapy and 10.99 per thousand 7 - 12 days after chemotherapy (P < 0.01).
      The mean PI of tumor cells before chemotherapy and 7 - 12 days after chemotherapy
      was 49.27% and 57.38% (P < 0.01). The mean AI of the high PI group increased more
      evidently than that of the low PI group. CONCLUSIONS: This treatment induced
      apoptosis of rectal cancer cells and inhibit tumor cell proliferation. The mean
      AI of the high PI group was higher than that of the low PI group. It is suggested
      that this operation should be performed shortly after chemotherapy.

PMID- 11832093
TI  - [Intraperitoneal lymphatic chemotherapy for colonic cancer].
AB  - OBJECTIVES: To evaluate the effect of intraperitoneal lymphatic chemotherapy with
      carboplatin and sandostatin on colonic carcinoma and abdominal lymphatic
      metastasis in patients after radical resection. METHODS: Patients with colonic
      cancer were divided into two group: abdominal lymphatic chemotherapy group and
      control group. The lymphatic chemotherapy group was treated at the introduction
      stage of anesthesia with carboplatin (200 mg) injected intraperitoneally and
      sandostatin (0.1 mg x 2) injected subcutaneously, whereas the control group was
      just treated with carboplatin (200 mg) injected intraperitoneally. The platinum
      levels in abdominal lymphatic nodes were monitored during operation. The two
      groups were uninterruptedly given intraperitoneal lymphatic chemotherapy or
      intraperitoneal chemotherapy. Retroperitoneal lymphatic metastasis was evaluated
      in each patient by abdominal CT scan after operation. RESULTS: The platinum
      levels in abdominal lymphatic nodes increased more significantly at 2, 3 hours in
      the lymphatic chemotherapy group than in the control group (P < 0.01). There was
      no difference in the platinum levels of the portal vein between the two groups,
      and also no difference in the platinum levels between the lymphatic nodes with or
      without metastasis. The rates of retroperitoneal lymphatic metastasis after
      resection were significantly lower in the lymphatic chemotherapy group control
      group (P < 0.01). CONCLUSION: Intraperitoneal administration of carboplatin
      combined with sandostatin may elevate the platinum levels in the abdominal
      lymphatic nodes and reduce the abdominal lymphatic metastasis after radical
      resection of colonic cancer. It is an effective method for intraperitoneal
      lymphatic chemotherapy.

PMID- 11832095
TI  - [Expression of matrix metalloproteinases and tissue inhibitor of
      metalloproteinases in colorectal neoplasm].
AB  - OBJECTIVES: To explore the relationship of matrix metalloproteinases (MMPs) and
      tissue inhibitor of metalloproteinases (TIMPs) to the oncogenesis and development
      of colorectal neoplasm. METHODS: RT-PCR was used to assay the level of MMP-2, MT1
      MMP, MMP-7, TIMP-2, TIMP-3 mRNA in 28 cases of colorectal cancer, including tumor
      tissue and surrounding normal tissue. RESULTS: MMP-2, MT1-MMP, TIMP-2 and TIMP-3
      were over-expressed in tumor and normal tissues, and MMP-7 was strong-expressed
      in tumor tissue but was weak-expressed only in one case of normal tissue. The
      expression of MMP-7 in tumor tissue was correlated to Dukes stage (P < 0.01). The
      expression of TIMP-2 in tumor tissue with positive-node was much higher than that
      with negative-node (P < 0.01). The expression of TIMP-3 was decreased with the
      Dukes stage and the depth of invasion (P < 0.01). There were no correlations
      between MMPs and TIMPs (P > 0.1). CONCLUSIONS: The expression of MMP-7 mRNA has a
      high specificity in colorectal cancer. MMP-7 may become a sensitive tumor marker.
      Inducing TIMP-2, TIMP-3 or suppressing MMP-2, MT1-MMP, MMP-7 mRNA's expressions
      may inhibit the invasion and metastasis of cancer.

PMID- 11832094
TI  - [Iodine-125 labeled monoclonal antibody 3H11: in radioimmunoguided surgery for
      primary gastric cancer].
AB  - OBJECTIVE: To evaluate the clinical usefulness of iodine-125 labeled monoclonal
      antibody (MAb) 3H11 in radioimmunoguided surgery (RIGS) for patients with gastric
      cancer. METHODS: Thirty-five patients with primary gastric cancer were enrolled.
      Via endoscopy, iodine-125 labeled MAb 3H11 was injected into submucosa around the
      tumor. All patients underwent surgery 4 to 11 days after administration.
      Intraoperative radioimmunodetection was performed using a hand-held gamma
      detecting probe. The counts of target sites were obtained, and tumor-to-normal
      tissue (T/NT) ratios were calculated. The T/NT ratio of 3.5:1 was taken as the
      lowest threshold value of positive gastric wall infiltration, and 3.0:1 for lymph
      node metastasis. Serial sections of those RIGS-positive lymph nodes, which were
      originally diagnosed as negative by routine histology, were made.
      Immunohistochemical staining was performed to detect the existence of lymphatic
      micrometastasis. RESULTS: Of thirty-five patients, 33 underwent RIGS
      successfully. The accuracy rate in detecting tumor infiltration of the incision
      margins was 97.0%, and the specificity 98.5%. In the group of patients with an
      interval of 6 to 8 days between injection and operation (n = 25), the RIGS
      results were satisfying. For the detection of lymphatic metastasis, the
      sensitivity of RIGS was 83.6%, the specificity 95.0%, and the accuracy 91.3%. The
      existence of lymphatic micrometastasis were verified immunohistochemically in
      52.6% (10/19) of those RIGS positive but histologically negative lymph nodes.
      CONCLUSION: This study validates the use of iodine-125 labeled monoclonal
      antibody 3H11 for the intraoperative detection of carcinomatous lesions in
      gastric cancer.

PMID- 11832096
TI  - [Expression of nm23 protein and estrogen receptor and prognosis of colorectal
      cancers].
AB  - OBJECTIVE: To explore the relationship between clinicobiological action and
      expression of nm23 protein and estrogen receptor (ER) for colorectal cancer.
      METHODS: The expression of nm23 protein and ER for 209 cases of colorectal cancer
      was detected by immunohistochemistry assay (LSAB). RESULTS: The expression of
      nm23 protein was correlated with that of ER for colorectal cancer (r = 0.5319, P
      < 0.01). The expression of nm23 protein and ER in colorectal cancers was not
      related with patient's age, sex, tumor position, pathological type, histological
      type, and Dukes stage (r < 0.4, P > 0.05). The expression was related with the
      prognosis of colorectal cancer (P < 0.01). The higher the expression of nm23
      protein and/or ER the better the prognosis, whereas the less the expression of
      nm23 protein and/or ER the worse the prognosis. CONCLUSIONS: The abnormal
      expression of nm23 protein is correlated with the disturbance of estrogen
      metabolism in colorectal cancer. The detection of nm23 protein and ER is helpful
      for the diagnosis and prognostic evaluation of colorectal cancer.

PMID- 11832097
TI  - [Expression of Fas ligand on peritumoral lymphocytes and its association with
      apoptosis of colorectal carcinomas].
AB  - OBJECTIVE: To study the expression of Fas ligand on peritumoral lymphocytes and
      its relation to the apoptosis of colorectal carcinoma. METHODS: The expression of
      Fas protein and FasL in 86 cases of colorectal carcinomas and normal colorectal
      tissues at the margins of resection was studied immunohistochemically. Apoptosis
      of cancer cells was evaluated with TUNEL method, which was then correlated with
      FasL expression on peritumoral lymphocytes. RESULTS: 53 (61.6%) of 86 cases of
      colorectal carcinoma were stained positively with Fas monoclonal antibodies, but
      such stain was net found in the normal colorectal tissues at the margin of
      resection. Peritumoral lymphocytes of 69 cases (80.2%) were stained positively
      with FasL antibodies. The intensity of FasL staining on peritumoral lymphocytes
      was positively correlated with the apoptotic index of cancer cells in the Fas
      positive colorectal carcinomas (P < 0.01), but not in the Fas negative group.
      CONCLUSION: FasL expressed on the surfaces of peritumoral lymphocytes mediates
      apoptosis of colorectal cancer cells by acting on its receptor, Fas protein on
      cancer cells. The elevation of Fas expression on cancer cells and application of
      specific Fas antibodies may serve as new approaches to treat colorectal
      carcinoma.

PMID- 11832098
TI  - [Surgery for patients with primary liver cancer: report of 1,038 patients].
AB  - OBJECTIVE: To investigate methods for enhancing safety of and improving the
      survival in patients with primary liver cancer (PLC). METHODS: One thousand and
      thirty eight patients with PLC were treated in our hospital from January 1990 to
      December 1998. The early period group (from January 1990 to December 1996)
      consisted of 731 patients [312 patients (42.7%) receiving liver resection]; the
      late period group (from January 1997 to December 1998) included 307 patients [217
      patients (70.7%) receiving liver resection]. RESULTS: The mortality within one
      month after hepatectomy was 2.24% in the early group and 0.74% in the late group.
      The 1-, 3- and 5-year survival rates were 73.1%, 54.2%, and 34.0% respectively in
      patients undergoing hepatectomy in the early group and 91.1%, 63.8% and 40.2% in
      the late group. CONCLUSIONS: Regular follow-up of high risk patients is helpful
      to discover small PLC. High proportion of small PLC, progress of perioperative
      management, and improvement of operative techniques including hepatopetal blood
      occlusion of half liver or in vitro-bypass through bio-pump during hepatectomy
      might be important approaches to enhance the safety of surgical treatment and
      improve the prognosis of patients with PLC.

PMID- 11832099
TI  - [Early arthroscopic reconstruction in treatment of acute complete rupture of
      anterior cruciate ligament].
AB  - OBJECTIVE: To early reconstruct acute and complete rupture of anterior cruciate
      ligament (ACL) and treat combined injuries for the recovery of knee joint
      stability. METHODS: Ten cases of acute complete rupture of anterior cruciate
      ligament and medial collateral ligament were treated arthroscopically by anterior
      cruciate ligament reconstruction using patellar tendon autograft fixed with
      interference screw from February 1998 to March 1999. RESULTS: Follow-up ranged
      from 5 months to 1 year and 3 months (average 10 months). Clinical results showed
      that the stability of knee joint was satisfactory in the early stage.
      CONCLUSIONS: Acute the ACL rupture can be reconstructed arthroscopically in the
      early stage and the injuries were moderate, combined injuries could be treated at
      the same time, and the stability of knee joint could recover in the early stage
      after operation.

PMID- 11832100
TI  - [Early soft tissue coverage in treatment of severe open tibial fractures].
AB  - OBJECTIVE: To study the role of early soft tissue coverage in the treatment of
      severe open tibial fractures. METHODS: 76 open tibial fractures of type III b
      were divided into early group (0 - 7 days), subacute group (8 - 30 days), and
      late group(> 30 days) according to the coverage time of soft tissue.
      Complications such as infection and nonunion were compared. RESULTS: The
      infection and nonunion rates of early group were lower than those of the subacute
      and late groups. The average time to union of the early group was less than that
      of the subacute and late groups. CONCLUSIONS: Early soft tissue coverage can
      reduce the complications and the time to union of severe open tibial fractures.
      The time for "early" coverage should be limited in 1 week. The opportunity of
      nosocomial infection will increase after 1 week.

PMID- 11832101
TI  - [Measurement of gastric emptying with Xianshizi in patients with resected
      esophageal cancer].
AB  - OBJECTIVE: To determine gastric emptying radiological in patients with esophageal
      cancer and to obtain a similar effect produced by radionuclide study. METHODS: A
      new product-Xianshizi (XSZ) made of the mixture of barium and silica gel was used
      quantitatively to evaluate gastric emptying. 17 patients with resected esophageal
      cancer before and after operation, and 7 healthy volunteers were studied.
      RESULTS: Preoperative patients had obviously delayed gastric emptying compared
      with the control group (P < 0.01). Postoperative patients had more delayed
      gastric emptying compared with themselves (P < 0.05). CONCLUSIONS: Postoperative
      gastroparesis is related to delayed gastric emptying. The results of this study
      were identical with those obtained by scintigraphy. Compared with isotope
      studies, X-ray exam after taking meal composed of XSZ may eventually contribute
      to detecting delayed gastric emptying quantitatively.

PMID- 11832102
TI  - [Middle-aged and elderly patients with hydronephrosis induced by ureteric
      obstruction: etiology and diagnosis].
AB  - OBJECTIVE: To improve the etiologic diagnosis of middle-aged and elderly patients
      with ureteric obstruction. METHODS: The etiology and diagnosis were
      retrospectively studied in 141 middle-aged and elderly patients with
      hydronephrosis in recent 10 years. RESULT: 59 patients had ureterolithiasis, 51
      ureteric cancer, 11 ureteric tuberculosis, 9 UPJ stricture, 6 uretero-cyst and 5
      ureteric polyp. CONCLUSIONS: Ureterolithiasis and ureteric cancer contribute
      greatly to ureteric obstruction in middle-aged and elderly patients.
      Etiologically, B ultrasonography is suggested to be used as the first choice in
      diagnosis and follow-up of the middle-aged and elderly patients with
      hydronephrosis, especially those accompanied with hematuria.

PMID- 11832103
TI  - [E-selectin and its ligand-sLeX in the metastasis of hepatocellular carcinoma].
AB  - OBJECTIVE: To study the significance of E-selectin and its ligand-sLeX in the
      metastasis of hepatocellular carcinoma (HCC). METHODS: Flow cytometry and
      immunohistochemistry were used to detect the expression of E-selectin and its
      ligand-sLeX in HCC cell lines and in human HCC tissues. RESULTS: The positive
      rate of E-selectin in vascular endothelial cells adjacent to cancer nest in
      tumors was 67.9% (19/28). In tumors accompanied with emboli or satellite foci, it
      was significantly higher than that without emboli or satellite foci (P < 0.05).
      The positive rate of E-selectin was not related to tumor size, tumor capsule,
      AFP, and the degree of differentiation. The positive expressions of sLeX in SMMU
      7721, PLC/PRF/5 and HepGII cell lines were 7.03%, 63.35% and 97.29% respectively.
      The positive cells of sLeX were mainly distributed in the margin of tumors; the
      positive expression of sLeX in HCC cells in emboli or invasive tumor tissues was
      much higher than that in primary foci. CONCLUSION: E-selectin and its ligand-sLeX
      are closely correlated with the metastasis of HCC.

PMID- 11832104
TI  - [Relationship between tumor suppressor gene p16 and Rb and early diagnosis of
      lung cancers].
AB  - OBJECTIVES: To study the incidences and mechanisms of tumor suppressor gene p16
      and Rb inactivation in lung cancers, and to investigate their relation to
      biological characters, clinical pathological diagnosis and gene classification
      diagnosis of lung cancers. METHODS: Immunohistochemistry, double in situ
      hybridization, PCR, PCR-SSCP and sequencing were applied to study the changes of
      p16 and Rb genes in 106 lung cancers and 23 lung tissues of benign diseases.
      RESULTS: Total expression rates of p16 and Rb proteins and mRNAs in lung cancers
      were lower than those in normal lung tissues and benign lung diseases, and they
      were specially related to histological type, metastasis and clinical stage of
      lung cancers. In stage I and II lung cancers, the obvious inactivation of tumor
      suppressor gene p16 or Rb was examined (32.6% or 28.3%); p16 inactivation was
      detected mainly in non-small cell lung cancers, and Rb inactivation mainly in
      small cell lung cancers. There were three mechanisms of homozygous deletions,
      methylations and mutations for p16 gene inactivation. The deletion rate of p16
      exon1 and/or exon2 was 25.8%, mainly took place in p16 protein negative cases of
      non-small cell lung cancers. 15 cases (16.9%) took part in methylations on SmaI
      sites of CpG island of p16 gene. PCR-SSCP and sequencing showed that 9 cases had
      p16 gene mutations. CONCLUSIONS: p16 and Rb genes may play important roles in
      genesis and progression of lung cancers. Inactivation of p16 or Rb gene may be is
      an early link of lung canceration, that is very important for early diagnosis of
      lung cancers. A new gene classification model for lung cancer diagnosis would be
      set up based on the research of p16 and Rb genes.

PMID- 11832105
TI  - [CDKN2/p16 gene cloning and its probe preparation and application in lung
      cancer].
AB  - OBJECTIVES: To clone CDKN2/p16(INK4a) gene, prepare its probe, and to study the
      change of CDKN2/p16(INK4a) gene in lung cancers. METHODS: Total RNA of normal
      lung tissue was extracted, CDKN2/p16(INK4a) gene cDNA synthesized, and
      CDKN2/p16(INK4a) gene recombinant vector, constructed. Southern blot was used to
      study CDKN2/p16(INK4a) gene in 46 cases of lung cancers, 3 cases of normal lung
      tissues, 6 cases of lung tissues near cancer, and 3 cases of lymph nodes with
      lung cancer metastasis. RESULTS: Cloned CDKN2/p16(INK4a) cDNA was proved by
      enzyme digestion and sequencing. Southern blot showed 4.3 kb band in normal lung
      tissues and lung tissues near cancers, and deletion of CDKN2/p16(INK4a) gene in
      cancer tissues and lymph nodes with lung cancer metastasis, with a deletion rate
      of 17.4% (8/46). CONCLUSION: CDKN2/p16(INK4a) gene may play a role to some extent
      in progression of lung cancers.

PMID- 11832106
TI  - [Measurement of T and DHT contents in normal and diseased human prostate
      tissues].
AB  - OBJECTIVE: To measure T and DHT contents in normal and diseased human prostate
      tissues. METHODS: Serum and prostatic T and DHT levels were measured in patients
      with normal, benign prostatic hyperplasia and prostate cancer. RESULTS: A decline
      was observed in serum T level, but no change in DHT concentration with aging.
      There were no significant differences in both blood T and DHT levels between the
      patients with BPH or PCA and normal controls. Serum T level remained constant.
      There were excessive accumulation of DHT in BPH, and cancerous prostate tissues
      were responsible for the pathogenesis of BPH and PCA. Finasteride treatment did
      not produce a reduction in prostatic DHT content. CONCLUSION: More than one form
      of 5a-reductases is responsible for the high level of DHT in the gland.

PMID- 11832107
TI  - [The development of degenerative disc animal model in rhesus monkey].
AB  - OBJECTIVE: To develop the degenerative disc animal model with histological and
      MRI observation. METHODS: Eight adult Rhesus monkeys were divided randomly into
      two groups after the lumbar discs MRI scan. The operated group, 6 monkeys, was
      subjected to annulus resection. A 5 mm x 3 mm cut was made in the left
      anterolateral part of the fibrosus annulus on L(4,5), L(5,6) and L(6,7) discs.
      The operated discs were scanned with MRI at 1 week, 4 weeks, 8 weeks, 13 weeks
      and 20 weeks postoperatively and observed histologically at 4 weeks, 8 weeks and
      20 weeks after operation. RESULTS: The histological structure of Rhesus monkey
      was similar to that of human being. The percentage of high signal intensity area
      in the operated discs reduced significantly at 8, 13, 20 weeks after operation (P
      < 0.05). The fibroplasia outside the annular tear could be observed in all 6
      operated discs at 4 weeks postoperatively. Two of 6 operated discs underwent
      fibroplasia at 20 weeks after operation. No heal evidence in the inner tear was
      showed after operation. CONCLUSIONS: The animal model for human lumbar disc
      degeneration could be obtained by anterio-lateral annulus resection. The early
      stage degenerative evidence could be observed without injury by measuring the
      percentage of the high intensity area of the operated discs on T2WI of MRI.

PMID- 11832108
TI  - [The invasive ability of bladder cancer].
AB  - OBJECTIVE: To find a direct method for testing the invasive ability of bladder
      cancer. METHOD: The invasive ability of 49 specimens of primarily cultured
      bladder cancer, transfected BIU-87 cells with pcDNA3-E1AF and untransfected BIU
      87 cells was evaluated by Matrigel invasion assay. RESULTS: Sixteen of the 49
      specimens were found to penetrate the matrigel barrier, and the result of the
      Matrigel invasion was related to the grade of the tumor cells. The number of
      positive cells of transfected BIU-87 was remarkably larger than that of
      untransfected BIU-87. CONCLUSIONS: Matrigel invasion assay is a simple, direct
      and dependable method, and could be used clinically to test the invasive ability
      of bladder cancer.

PMID- 11832109
TI  - Rehabilitative therapy of short bowel syndrome: experimental study and clinical
      trial.
AB  - OBJECTIVES: To investigate the effect of growth hormone on proliferative activity
      of the residual small intestinal mucosa after massive small intestinal resection
      and to evaluate the clinical efficacy of bowel rehabilitative therapy for short
      bowel syndrome. METHODS: Small intestinal mucosa proliferative activity were
      compared in rats from control group (sham operation), short bowel group (80%
      small bowel resection) and growth hormone treatment group (80% small bowel
      resection + growth hormone 1 U x kg(-1) x d(-1) for 28 days) with the aid of
      histology image analysis, flow cytometric assay, immunohistochemistry analysis
      and RT-PCR assay. The nutritional status, D-xylose absorption and stool nitrogen
      output were observed in 9 consecutive parenteral nutrition dependent patients
      with short bowel syndrome after intestinal rehabilitative therapy (growth hormone
      8 - 12 U x kg(-1) x d(-1) im + glutamine 0.6 g x kg(-1) x d(-1) iv + special
      diet) for 21 continuous days. RESULTS: Growth hormone administration
      significantly increased rat small intestinal mucosal villous height, mucosal
      thickness, proliferative index, and the expression of proliferating cell nuclear
      antigen and c-jun mRNA. Rehabilitative therapy increased the body weight, serum
      total protein and album in concentrations in patients. Their D-xylose absorption
      indices increased and fecal nitrogen losses decreased. Follow-up data showed that
      6 of the 9 patients sustained on enteral nutrition. CONCLUSION: Growth hormone
      enhances the proliferative activity of the mucosal epithelium and bowel
      rehabilitative therapy may benefit the patients with short bowel syndrome.

PMID- 11832110
TI  - [Results: of 2000 kidney transplantations].
AB  - OBJECTIVE: To analyze the clinical results of renal transplantations. METHODS:
      From 1973 to 1999, 2000 renal transplantations were performed in 1 739 (1 238
      males and 501 females) patients with end-stage renal failure. We analyzed the
      graft survival rates at 1, 3, 5 years; the main factors contributing to the
      mortality; the factors affecting the survival rate of re-transplant grafts;
      features of cancers after renal transplantation; the effect of CsA on liver
      function after renal transplantation; the treatments of chronic rejection; the
      effect of HLA typing on renal transplantation. RESULTS: The graft survival rates
      at 1, 3, 5 years were 87.33%, 80.17% and 67.04% respectively after using CsA
      since 1985. 282 recipients were over 50 years. The year graft survival rate was
      82.27% and the 1-year patient survival rate was 84.75%. Pneumonitis was the
      dominant factor of death after renal transplantation, the incidence was 4.49%,
      and the death rate was 34.62%. The incidence of CMV positive after renal
      transplantation was 40.30%, and the death rate was 8.03%. Patients should wait a
      longer period (over 6 months) if the first transplant was failed because of acute
      rejection. The incidence of tumor after transplantation was 1.46%. The most
      frequent site of the tumors was urological system. The patient's liver function
      before transplantation and the intraindividual variability of CsA were the major
      factors on toxicity of the liver. The incidences of acute rejection were 27%,
      35.5%, 22.4%, 20.85%, 0%, 0% respectively when the HLA mismatches were 6, 5, 4,
      3, 2 and 1. CONCLUSION: Using immunosuppressants reasonably, preventing acute
      rejection, achieving good HLA typing are the major factors improving long-term
      graft/patient survival rate.

PMID- 11832111
TI  - [Survival analysis after kidney transplantation in 1,180 cadaveric graftings].
AB  - OBJECTIVE: To analyze the outcome of twenty-two years of cadaveric kidney
      transplantation and the predict factors impacting on graft survival. METHODS: The
      data of 1,180 cadaveric kidney graftings in 1,039 patients between October of
      1977 and June of 1999 were summarized by calculation of patient and graft
      survival rates using Kaplan-Meier product limit estimates. 13 factors that may
      influence on graft survival were analyzed by the log-rank and Cox model. RESULTS:
      The total of 1-, 5-, 10-, 15-, and 20-year patient survival rates were 93.02%,
      80.25%, 67.86%, 65.34% and 65.34%, and the corresponding graft survival rates
      88.6%, 68.3%, 43.8%, 43.8%, and 32.8%, respectively. Graft half-life was (13.98
      +/- 0.96) years. The longest survivor was 22 years after cadaveric kidney
      transplantation. The quality of life after grafting in 835 alive patients was
      improved apparently; 95% of them had a normal graft function and 85% returned to
      work. The result of multivariable analysis using Cox model showed that 8 factors
      of patient's age, grafting time, pretransplant blood transfusion, cold ischemia
      time, delayed graft function, time of normal graft function, immunosuppressive
      regimen, and acute rejection were very important to affect the graft survival.
      CONCLUSION: Cadaveric kidney transplantation is a successful and effective method
      to rescue the patients with end-stage renal disease.

PMID- 11832113
TI  - [Kidney transplant patients with hepatitis C virus infection:clinical,
      pathologic, and immunohistochemical study].
AB  - OBJECTIVE: To evaluate the clinical results of kidney transplant patients with
      hepatitis C virus (HCV) infection. METHODS: We tested the sera from 67 patients
      for anti-HCV and HCV RNA using second generation ELISA and Nest-PCR; HCV-NS3, NS5
      were tested by immunohistochemistry LSAB. All patients were followed up for 1
      year. RESULTS: The prevalence of anti-HCV was 50.75% (n = 34), and the rate of
      HCV RNA was 47.76% (n = 32). The HCV RNA positive group had a much longer
      duration of dialysis and had received more blood transfusion than HCV RNA
      negative group before transplantation. ALT levels and prevalence of liver
      dysfunction were significantly higher in HCV RNA positive group after
      transplantation; however, there was no difference in infection, rejection, graft
      survival and serum creatinine level. LSAB suggested that HCV-NS3, NS5 antigen of
      two from three liver bioptic specimens with HCV RNA positive patients were
      positive. CONCLUSIONS: HCV infection in renal transplant patients can result in
      liver disease, and is not significantly associated with infection, rejection, and
      graft survival within a short time. We consider HCV not a contraindication to
      renal transplantation.

PMID- 11832112
TI  - [Simultaneous pancreas-kidney transplantation for the treatment of type I
      diabetes with end-stage renal disease].
AB  - OBJECTIVE: To demonstrate whether simultaneous pancreas-kidney transplantation is
      practical for the treatment of Type I diabetes with end-stage renal disease.
      METHODS: Eight cases of combined pancreas-kidney transplantation were performed
      in our institute. The age ranged from 35 years to 48 years (average 43.46 years).
      All cases were diagnosed as type I diabetes with end-stage nephropathy, two cases
      with blindness due to retinopathy. The case history ranged from 2 years to 22
      years. Pancreas allograft was placed in the right iliac fossa with pancreas
      exocrine drainage to bladder, whereas renal allograft the in left iliac fossa.
      Initial immunosuppression regimen is quadruple. RESULTS: Seven patient could be
      insulin free after transplantation, with normal fasting blood glucose. One
      patient received insulin treatment for 40 days after operation. One patient
      survived 1 year and 9 months after transplantation with normal functioning
      pancreas allograft and kidney allograft. Four patient survived 2 months with
      normal allograft function. Fasting blood glucose was between 4.5 and 6.2 mmol/L;
      Cr was between 53 and 106 micromol/L. Diet control was not necessary. Two patient
      died of encephalorrhagia, and 1 pancreatic vascular thrombosis and necrotic
      pancreatitis. CONCLUSIONS: Combined pancreas-kidney transplantation is feasible
      to treat type I diabetes with end-stage nephropathy. Functional pancreas
      allograft could be procured in the present condition. Pancreatic exocrine is
      drained to bladder. The diagnosis of acute rejection could be made earlier by
      detecting urine amylase. Heparin should be added in order to prevent pancreatic
      thrombosis.

PMID- 11832114
TI  - [Acoustic densitometry for quantification of renal allografts microcirculation
      and microstructure].
AB  - OBJECTIVE: To establish a new method for observing renal allografts
      microcirculation and microstructure with acoustic densitometry (integrated
      backscatter, contrast, second harmonics). METHODS: 27 patients with renal
      allografts were investigated by Doppler, IBS, contrast and second harmonics.
      Renal allografts failed age in 5 patients 20-61 years. Intravenous injection of
      SHU-508A was given, compared with pre-injection by quantitative assessment of
      acoustic densitometry (AD) of renal microstructure. RESULTS: There was a
      significant difference in the peak intensity, the area under the curve and the
      half-time of wash-out between pre-injection and injection contrast agent. The
      wish-in and wish-out curve was shown in a peak shape. The renal allografts with
      acute rejection were significantly lower than the control group in AD (P < 0.05).
      No contrast opacification of renal microstructure was present in 5 failed renal
      allografts and the wish-in and wish-out curve appeared in a straight line shape.
      CONCLUSION: AD is safe, and efficient in assessing renal allografts
      microstructure. It more sensitive in detecting allograft complication such as
      rejection than Doppler.

PMID- 11832115
TI  - [MR urography: technique and clinical application in patients with kidney
      transplantation].
AB  - OBJECTIVE: To assess the value of magnetic resonance urography (MRU) for the
      noninvasive postoperative evaluation of renal transplants. METHODS: 28 cases of
      renal transplantation were examined with a modified, heavily T2-weighted fast
      apin-echo pulse sequence and fat-suppression pulse aid. Post-procedure processing
      was performed with a maximal-projection (MIP) algorithm. RESULTS: 28 patients
      were studied. MRU revealed abnormal finding in 9 patients: mild dilatation of the
      renal pelvis without any urodynamic relevant obstruction (2), moderate dilatation
      of the renal pelvis (3), acute rejection (3), and ATN (1). Ureteral stenosis was
      diagnosed in 1 patients and treated surgically. CONCLUSIONS: MRU is an
      alternative to conventional urinary tract images techniques. It requires no
      radiation or iodinated contrast material. It is reliable and noninvasive in
      depicting the urinary tract. MRU can be used as a noninvasive technique for
      assessment of renal transplantation in cases suspicious of complication in the
      excretory system.

PMID- 11832116
TI  - [Tracheal transplantation].
AB  - OBJECTIVE: To treat long tracheal cancer by tracheal transplantation. METHODS: In
      March 17, 1999, a patient received a total laryngeal resection and a resection of
      8 cm upper and middle trachea, which was replaced by a 6 cm long trachea of
      another donor. The donor trachea was dipped first in preservation liquid A for
      sterilization for 24 hours, then in preservation liquid B for over 48 hours for
      destructing MHC. Pedunculated greater omentum and pedunculated greater pectoral
      musculus supplied the blood for the donor trachea. One side of the donor was
      anastomosed with the lower trachea, and the other with the neck skin. RESULTS:
      The patient survived 300 days after operation. The auto tracheal membrane covered
      the donor surface; auto- and xeno trachea was well anastomose. The new trachea
      grew very well. CONCLUSION: Trachea transplantation is possible the best method
      to treat long tracheal disease if the transplantable trachea is less 5 cm.

PMID- 11832117
TI  - [Long-term follow-up results of microsurgical treatment for glossopharyngeal
      neuralgia].
AB  - OBJECTIVE: To discuss effective surgical methods for the treatment of
      glossopharyngeal neuralgia. METHODS: During 1986 - 1998, 21 patients with
      glossopharyngeal neuralgia were treated microsurgically. Of whom, 5 patients were
      treated by microvascular decompression (MVD), 4 by MVD combined with rhizotomy of
      glossopharyngeal nerve root and upper 1st to 2nd rootlets of vagus nerve root,
      and 12 by rhizotomy of glossopharyngeal nerve root and upper 1st to 2nd rootlets
      of vagus nerve root. RESULTS: Neuralgia disappeared in all patients
      postoperatively. In 3 patients, occasional coughing episodes occurred
      postoperatively. One of the 3 patients also suffered from mild hoarseness and
      swallowing difficulty. All patients were followed up on average 7.2 years with no
      recurrence. CONCLUSIONS: MVD, rhizotomy of glossopharyngeal nerve root and upper
      1st to 2nd rootlets of vagus nerve and their combination are effective for the
      treatment of glossopharyngeal neuralgia. Operative methods should be chosen
      according to the following two points: compression of nerve roots by affected
      vessels or not; and the condition of compression.

PMID- 11832118
TI  - [Effect of combined operation including splenorenal shunt as the main technique
      for portal hypertension in children].
AB  - OBJECTIVE: To assess the effect of combined operation including splenorenal shunt
      as the main technique for portal hypertension in children. METHODS: 22 patients
      were reviewed and followed up from 1980 to 1998 (13 male, 9 female). The average
      age was 9.45 years. Intrahepatic type was shown in 16 patients and prehepatic
      type in 6. All patients had hematemesis, hematochezia or severe esophageal
      varices. Liver function was classified Child A in 14 patients, B in 7, and C in
      1. Combined operation was performed in all patients. RESULTS: There was no
      operative death in this group. 21 patients (95.5%) were followed up, with the
      longest time for 19 years (average 9.58 years). Six patients had hemorrhage from
      the esophageal varices after operation, and two died of hemorrhage. The survival
      rates of < 3, -5, -10, -15, > 15 years were 95.2%, 100%, 93.8%, 100%, 100%
      respectively. No hepatic encephalopathy was noted. CONCLUSION: In treating and
      preventing hemorrhage from the esophageal varices, combined operation including
      splenorenal shunt as the main technique is the first choice for the portal
      hypertension in children. Attention must be paid to the patients who had
      hemorrhage from the esophageal varices after operation.

PMID- 11832119
TI  - [Treatment of spondylolisthesis with pedicle screw instrumentation and anterior
      or posterior lumbar interbody fusion].
AB  - OBJECTIVE: To investigate the treatment of spondylolisthesis with pedicle screw
      instrumentation and anterior or posterior lumbar interbody fusion. METHODS: 26
      patients, 14 males and 12 females, underwent spinal instrumentation with RF or
      SOCON instrumentation and anterior or posterior interbody fusion with TFC. Among
      them, 6 patients underwent RF instrumentation and posterior interbody fusion with
      TFC, 15 SOCON instrumentation and posterior interbody fusion with TFC, and 5 RF
      instrumentation and anterior interbody fusion with composite cortical ring.
      RESULTS: All the patients were followed up for an average of 22 months (range 6 -
      18 months) after operation. The reduction of spondylolisthesis was 88%, and the
      fusion rate 89%. There was no recurrence of spondylolisthesis. CONCLUSIONS: High
      quality SOCON instrumentation may be reliable for the treatment of
      spondylolisthesis. Implantation of TFC into the interbody space can stabilize the
      fused segments, prevent the collapse of the interbody space, avoid bone
      resorption, remain or increase the heights of the interbody space, facilitate the
      union of the fused segments, and allow early mobilization.

PMID- 11832120
TI  - [Surgical treatment of single level unstable degeneration with foraminal
      stenosis].
AB  - OBJECTIVES: Lumbar spine single level unstable degeneration with foraminal
      stenosis was treated with unilateral decompression, disc excision, posterolateral
      interbody fusion utilizing single BAK cage and count-lateral facet joint screw
      fixation. The short-term and mid-term clinical results were evaluated. METHODS:
      There were thirty patients (13 male, 17 female) with an average age of 46.5
      years. From posterior approach, all patients underwent unilateral decompression,
      disc excision, interbody fusion with posterolateral inserted single BAK cage, and
      count-lateral facet joint screw fixation. RESULTS: All patients underwent surgery
      safely without severe complications occurred such as infection and neurological
      damages. The average follow-up time was 12 months (6 - 18 months) with complete
      relief of symptoms. Solid fusion was achieved in all but 2 patients at final
      follow-up. 90% of the patients obtained successful clinical outcome. CONCLUSIONS:
      Complete decompression of the neural foramen can relief the symptoms, and
      interbody fusion utilizing threaded cage can restore the height of disc space and
      withstand axial loading of the spine. Addition of the facet joint fixation
      increased the postoperative segment stability and enhances solid fusion. With
      less invasive and preservation of part of the posterior elements of the lumbar
      spine and the solid fusion achieved, we consider it a sound procedure for the
      treatment of single level unstable degeneration with foraminal stenosis of lumbar
      spine. Long-term follow-up results needs to be observed.

PMID- 11832121
TI  - [Remodelling of the spinal canal after thoracolumbar burst fractures:
      significance of nonoperative management].
AB  - OBJECTIVES: To determine the phenomenon of remodelling of the spinal canal after
      thoracolumbar burst fracture and to investigate the efficacy of nonoperative
      management. METHODS: A total of 31 patients with thoracolumbar burst fractures,
      including 7 untreated, 16 treated nonoperatively, and 8 treated operatively, were
      retrospectively analysed and followed up for 3 to 7 year. The initial and final
      degrees of neurological deficit and stenotic ratio of the spinal canal were
      recorded. RESULTS: The stenotic ratio significantly decreased (P < 0.01) from the
      discharge (range: 12.3% to 74.5%, average: 26.2%) to the final follow-up (range:
      5.4% to 46.5%, average: 19.2%), but there were no differences (P > 0.05) of
      stenotic ratio improvement among the patients untreated, and treated
      nonoperatively and operatively, or among the patients with different degree of
      neurological deficit. CONCLUSIONS: Significant remodelling of the spinal canal
      develops after thoracolumbar burst fractures. Nonoperative management may be
      taken into account for treatment of neurological intact patients with
      thoracolumbar burst fractures.

PMID- 11832122
TI  - [Ultrastructural study on the peripheral nerve and skeletal muscle of patients
      with spastic cerebral palsy].
AB  - OBJECTIVE: To explore pathological features of the peripheral nerve and skeletal
      muscle of patients with spastic cerebral palsy. METHODS: The peripheral nerve and
      skeletal muscle of 25 patients with spastic cerebral palsy were observed by gross
      examination during operation, and under microscope and electron microscope.
      RESULTS: Gross examination showed that peripheral nerve and skeletal muscle was
      normal during operation. Microscope showed that some skeletal muscle fibers
      degenerated, and the connective tissue proliferated. electronmicroscopically the
      damage of demyelination was extensive on the peripheral nerve; the pathological
      changes of Schwann's cell were sooner and more severe than axons; the
      pathological changes of myelinated nerve fiber were more obvious than the
      nonmyelinated nerve fiber; the lymphocyte were found around the microvasculature
      within the perineurium; the mitochondrion of skeletal muscle fiber increased in
      number, the sarcoplasmic reticulum and transverse tubule decreased and developed
      badly, the degenerative muscle fiber showed cell edema or the pathological
      changes of myofibril. All the peripheral nerve and skeletal muscle fiber affected
      had no repair and regeneration. CONCLUSIONS: The demyelination of the peripheral
      nerve of patients with spastic cerebral palsy is primary, and the skeletal muscle
      of patients with spastic cerebral palsy is secondary pathological change. The
      activity of nerve and muscle regeneration is bad.

PMID- 11832123
TI  - [Washing liquid cytology examination of operative wound in patients with breast
      tumor].
AB  - OBJECTIVES: To study the relation between exfoliated tumor cells in operative
      wound and clinical pathologic classification and to provide theory for killing
      exfoliated tumor cells in operation. METHOD: Washing liquid cytology examination
      of the operative wound was done in 262 patients with breast tumor. The relation
      between cytology examination and pathological classification was analyzed.
      RESULTS: In the 262 patients, exfoliated tumor cells were found in 63 patients,
      (24%). The detection rate in patients with I, II, III and IV stage was 5.3%,
      27.1%, 79.3% and 100% respectively; The rate for T(1), T(2), T(3) stage was 6.1%,
      18.9% and 51.3% respectively. The detection rate was 58.6% when the number of
      metastasis lymph node beyond 3; the rate was 14.3% and 14.1% respectively when
      the number below 3 or no lymphatic metastasis. CONCLUSION: The detection rate of
      exfoliated tumor cells is related to tumor advance, and it is necessary to kill
      exfoliated tumor cells in operation.

PMID- 11832124
TI  - [Relationship between estrogen receptor and Graves' disease].
AB  - OBJECTIVE: To study the relation of expression of estrogen receptor (ER) in
      thyroid tissues with Graves' disease (GD). METHODS: ER was detected in the
      tissues of 40 patients with GD and 15 patients with normal thyroid by
      immunohistochemical method. Gene expression of ER was studied in frozen slides of
      26 GD thyroids and 10 normal thyroids by fluorescence in situ hybridization
      (FISH) together with image analysis system. RESULTS: In immunohistochemical
      detection, the positive rate of ER in GD group was 70% (28/40), but 13.3% (2/15)
      in the control group (P < 0.01). The positive degree of ER in female with GD was
      higher than that in male with GD (P < 0.05). The positive rate of ER in the
      female GD group below 35 years was 85.0% (17/20) and 50% (5/10) in the female GD
      group above 35 years (P < 0.05). In FISH, the optical density (A) value of the
      female GD group was 30.14 +/- 10.74, and in the male GD group 21.06 +/- 7.71, but
      in the control group it was 16.91 +/- 5.30 (P < 0.01). The A value of the female
      GD group below 35 years was 33.85 +/- 10.10, and 23.24 +/- 7.48 in the female GD
      group above 35 years (P < 0.05). CONCLUSIONS: The increasing of ER content is
      related to the development of GD. Estrogen may be a promoting factor for GD. The
      sex and age differences in GD development are associated with the effects of
      estrogen and ER.

PMID- 11832125
TI  - [Improvement of protein metabolism by glutamine-enriched TPN and growth hormone
      in recipients of rat small bowel transplantation].
AB  - OBJECTIVE: To observe the effect of glutamine-enriched TPN and recombinant human
      growth hormone (rhGH)on protein metabolism of recipient of rat small bowel
      transplantation. METHODS: Twenty four recipients of rat allogeneic heterotopic
      small bowel transplantation (SD-->Wistar rat) were divided into 4 groups randomly
      according to the presence or absence of glutamine or rhGH in TPN regimen.
      Cyclosporine A (CsA) was used as the immunosuppressant. The changes of body
      weight, nitrogen balance, urinary 3-methyl histidine excretion and plasma albumin
      level during 14 days after transplantation were observed. RESULTS: Applications
      of glutamine-enriched TPN or rhGH decreased the postoperative catabolism of
      protein of recipients. They promoted protein synthesis and positive nitrogen
      balance so as to minimize the loss of body weight and correct hypoalbuminemia.
      They were synergistic to other. CONCLUSIONS: Glutamine-enriched TPN and rhGH can
      promote the protein metabolism of rat small bowel transplantation recipients
      effectively with the use of CsA, so as to improve the recovery of general
      condition. Their combination may have the synergistic effect.

PMID- 11832126
TI  - [The prevention of infection complicating acute necrotizing pancreatitis:an
      experimental study].
AB  - OBJECTIVE: To observe the effects of 5 intervention measures on infection
      complicating acute necrotizing pancreatitis (ANP) in dogs and rats. METHODS: A
      lethal model of ANP was reproduced by infusion of artificial bile into the
      biliopancreatic duct. Animals were divided randomly into: ANP group (no
      treatment); Chinese medicine group ("Qing Yi Tang"); Bifidobacterium mixture
      group; purgation group (MgSO(4)); selective decontamination of the digestive
      tract (SDD) group; and somatostatin group. The pancreas and intestine were
      observed morphologically and tight junction on ileum epithelia was assessed on
      cryofracture replicas. Blood and/or tissue levels of DAO and D-lactic acid and
      uric contents of lactulose/mannitol (L/M), served as indicators of gut barrier
      function, were measured at various time points. Intestinal flora and incidence of
      bacterial translocation (BT) to organs were examined. RESULTS: In early stage of
      ANP, mucosal and epithelial tight junction damage and flora disturbance occurred
      in the gut. In addition, the gut barrier function indicators deteriorated. The BT
      rates were as high as 78.6% (canine) and 59.5% (rat). Treatment with Chinese
      medicine markedly improved gut barrier function and reduced BT rate (32.1% -
      37.0%). Having similar purgative response as Chinese medicine, MgSO4 did not show
      any beneficial effect on gut barrier protection and the incidence of BT was not
      reduced. In bifidobacterium mixture and SDD group, flora balance was preserved
      well and similar results as Chinese medicine were obtained. The BT rates of these
      two groups decreased to 33.9% and 33.3%, respectively. Somatostatin markedly
      blunted pancreatic tissue injury and ameliorated gut barrier damage during early
      phase of ANP. All intervention measures except for purgation also decreased
      mortalities (14.3% - 35.3%, compared with 58.8% of the no treatment group).
      CONCLUSIONS: Treatment with Chinese medicine, bifidobacterium mixture, SDD and
      somatostatin attenuated gut barrier damage and BT after ANP, and could be used to
      prevent secondary infection after ANP, but purgation alone is not effective.

PMID- 11832127
TI  - [Multiple organ dysfunction syndrome after open chest wound and seawater
      immersion: experimental study].
AB  - OBJECTIVE: To evaluate the effect of seawater immersion on multiple organ
      dysfunction syndrome (MODS) after chest trauma. METHODS: Twenty health dogs were
      divided into two groups. Right open pneumothorax was induced in both control
      group (n = 10) and experimental group (n = 10). After induction of chest trauma,
      animals in the experimental group were immersed in artificial seawater. Blood
      samples were taken at seven different intervals for assessing blood gas, plasma
      level of TNFalpha, and IL-1 beta. Changes of serum alanine aminotransferase
      (ALT), aspartate amino-transferase (AST), creatine kinase (CK) lactate
      dehydrogenase (LDH) and creatinine (Cr) were measured. At the end of study, lung
      was harvested for assessing lung water content and ratio of wet weight and dry
      weight. RESULTS: A significant elevation of ALT, AST, CK and LDH was observed in
      both groups. Organ functional parameters in the experimental group were
      consistent with the failure standard at 30 minutes after seawater immersion, and
      those in the control group at 4 hours. Post-trauma mortality and incidence of
      MODS were much higher in the experimental group than those in the control group
      (P < 0.01). The plasma levels of TNFalpha and IL-1 beta significantly increased
      at 30 minutes and reached the highest level at 60 minutes after seawater
      immersion. The time of peak level appeared earlier in the experimental group than
      that in the control group. CONCLUSION: Seawater immersion after open chest trauma
      results in high incidence of MODS and high mortality rate due to progressive
      dysfunction of multiple organs.

PMID- 11832128
TI  - [Pericardial devascularization with splenectomy for the treatment of portal
      hypertension].
AB  - OBJECTIVE: To review our experiences in and evaluate the efficacy of pericardial
      devascularization with splenectomy for the treatment of portal hypertension.
      METHODS: From May 1972 to October 1999, 508 patients with portal hypertension
      were treated with this operation. 319 of them had posthepatitic cirrhosis, and
      141 late stage schistosomiasis or accompanied chronic viral hepatitis. RESULTS:
      The bleeding control rate was 94.1%, and the overall operative mortality rate was
      4.5%. The major causes of death were upper gastrointestinal bleeding,
      intraabdominal hemorrhage, hepatic failure and hepatorenal syndrome. The mean
      follow-up time was 3.8 years. The 5-year survival rate was 94.1%, and the 10-year
      survival 70.7%. The 5-year recurrent bleeding rate was 6.2%. The 10-year
      recurrent bleeding rate was 13.3%. The rate of postoperative hepatic
      encephalopathy was 2.5% at 5 years, and 4.1% at 10 years. CONCLUSIONS:
      Pericardial devascularization with splenectomy was the first choice for the
      treatment of portal hypertension, especially for posthepatitic cirrhosis. The
      following were our experience: (1) thorough porto-azygos disconnection; (2)
      performing the operation in according to pericardial anatomy with correct
      surgical techniques; (3) selection of operative candidates and opportunity; (4)
      emphasizing perioperative management and preventing complications.

PMID- 11832129
TI  - [Surgical treatment of left main stenosis in coronary artery disease].
AB  - OBJECTIVE: To study the efficacy of surgical treatment in the patients with left
      main stenosis of 50% or more. METHODS: Forty-two patients with left main stenosis
      (LMS) underwent coronary artery bypass grafting (CABG). Their mean age was 68.7
      years. 16 patients had 50% to 75% LMS and 26 patients more than 75%. Twenty-nine
      patients had unstable angina. Seventeen patients with angina were in class III
      according to CCSS and 18 were in class IV. Preoperative left ventricular ejection
      fraction in 24 patients was beyond 50%. RESULTS: The mean preoperative hospital
      stay was 2.3 days. The mean number of grafts was 3.3 per patient. There was no
      operative death. The patients were all free from angina postoperatively. The mean
      follow up time was 42 (3 to approximately 78) months without death. CONCLUSIONS:
      Coronary artery bypass grafting is the first choice to treat left main stenosis.
      It is a safe and effective method. To determine properly the time of surgical
      intervention is helpful to reduce preoperative cardiac affairs and improve
      operative efficacy.

PMID- 11832130
TI  - [Off pump coronary artery bypass grafting in 51 cases].
AB  - OBJECTIVE: To study the cost-effective minimal invasive coronary bypass surgery
      which decreases the complication associated with cardiopulmonary bypass,
      alleviates postoperative pain, and promotes recovery. METHODS: From August 1998
      to November 1999, fifty-one patients underwent minimal invasive coronary bypass
      surgery with off pump technique. Age range was from 39 to 80 years (average 64).
      Thirty-five patients suffered from myocardial infarction and nine patients
      diabetes. Left ventricular ejection fraction was from 20%-72% (average 53%). All
      procedures were completed through medial sternotomy. Stabilizers of CTS, Octopus,
      and USSC were applied. The average graft was 2.7 per case. RESULTS: The operative
      mortality was 1.9%. The average ICU and hospital stay were 1.2 and 6 days,
      respectively. The average chest drainage and blood transfusion were 415 ml and
      160 ml, respectively. Fifty patients survived from surgery. All survived patients
      had no symptoms of angina during the short-term follow-up (1 to 8 months). Two
      patients were followed up by postoperative coronary angiography, which showed a
      satisfactory anastomosis rate of 100%. CONCLUSIONS: Minimal invasive coronary
      bypass surgery is safe, cost-effective, and suitable for patients with high risk
      of extracorporeal circulation. It can also be used for multivessel disease.

PMID- 11832131
TI  - [Surgical repair of postinfarction ventricular septal rupture].
AB  - OBJECTIVE: To study the characteristics of occurrence of postinfarction
      ventricular septal rupture (VSR) and preliminarily evaluate the proper timing of
      operation and its effect. METHODS: Twenty patients with postinfarction VSR were
      divided into two groups: surgical repair (14 patients), and conventional
      treatment (6 patients). Clinical data were analyzed and the 14 patients were
      followed up for 4 months-14 years. RESULTS: The 6 patients died within 6 hours-7
      days. Of the 14 patients treated surgically, however, 4 had their ruptures closed
      by the technique of plication and the rest by prosthetic patches. Concomitant
      procedures included resection of postinfarction ventricular aneurysm in all 14
      patients and coronary artery grafting bypass in 3. Five patients (35.7%) died
      during peri-operation, and 14.3% had residual ventricular septal defects. 2
      patients died of heart failure 7 and 9 years after the operation respectively, 1
      was lost to follow-up, and the rest were in good condition. CONCLUSIONS: The
      proper timing of operation determined by the cardiac function of patients. It is
      necessary to improve condition of circulation before operation. The mortality
      rate of emergency operation is high within 3 days after VSR, and residual VSR
      tends to develop in a week after the repair. Operation should be performed a week
      after VSR. The early operative mortality is closely related to preoperative
      cardiogenic shock and postoperative complications.

PMID- 11832132
TI  - [Surgical treatment of anomalous origin of the left coronary artery from the
      pulmonary artery].
AB  - OBJECTIVE: To introduce the experience in surgical correction of anomalous origin
      of the left coronary artery from the pulmonary artery in 8 patients. METHODS:
      From 1991 August to 1999 March, 8 patients underwent surgery. Intrapulmonary
      tunnel procedure was performed in 7 patients, and coronary artery bypass grafting
      using the saphenous vein in 1. Mitral valve incompetence was repaired in 1
      patient. ECG, echocardiographic and angiographic studies were made in all
      patients. 7 patients were followed up for 327 months (mean 46.8 +/- 10.7) months.
      RESULTS: No hospital deaths and later deaths occurred nor major complications
      during hospitalization. Because of suture of intrapulmonary tunnel loose, artery
      pulmonary artery leakage 1 patient was reoperated on successfully. Follow-up
      showed cardiac function New York Heart Association function class I, mean LVMD
      (46.4 +/- 3.7) mm, vs mean (54.4 +/- 2.8) mm before the operation (P < 0.01), and
      mean EF (69.4 +/- 2.3)% vs mean 59.6% +/- 2.8% before the operation (P < 0.05).
      CONCLUSIONS: Anomalous origin of the left coronary artery from the pulmonary
      artery is a very rare congenital malformation. To correct the anomalous origin of
      the left coronary artery from the pulmonary artery is to reconstruct the normal
      two-coronary system and to treat the other associated diseases. Intrapulmonary
      tunnel operation is easy to perform satisfactorily.

PMID- 11832133
TI  - [Radial artery for coronary artery bypass grafting: operative techniques and
      early results].
AB  - OBJECTIVE: To review the experience coronary artery bypass grafting (CABG) with
      the radial artery (RA) performed from June 1997 to December 1999. METHODS: A
      total of 71 patients received CABG in whom the performance of the radial and
      ulnar arteries were checked preoperatively with the modified Allen's test. A
      curvilinear skin incision was made from 3 cm distal to the cubital fossa to 2 cm
      before the proximal crease at the wrist. The RA was mobilized together with its
      satellite veins and surrounding fat tissues. Small branches were divided between
      titanium clips. Direct touching on the RA trunk was totally avoided and use of
      diathermy was minimized. A 1% papaverine solution of heparinized Ringer's was
      applied intraluminally into the free RA graft before it was stored in the same
      solution for later use. Seventy-two RAs were harvested and 79 distal anastomoses
      were made mostly to the posterior descending branches and the circumflex marginal
      branches. All the proximal anastomoses were directed to the aorta. Calcium
      channel blockers were routinely used for a period of 6 months postoperatively.
      RESULTS: There was 1 death for an operative mortality of 1.4%. The death was not
      caused by failure of RA graft. There was no compartment syndrome or hand
      ischemia. No perioperative myocardial infarction was observed. CONCLUSIONS: It is
      easy and safe to use the RA for CABG by which good results can be achieved. A'no
      touch' harvesting technique and use of calcium-channel blockers are essential to
      the functioning of this conduit.

PMID- 11832134
TI  - [Clinical results of transmyocardial laser revascularization for 77 patients with
      coronary artery disease].
AB  - OBJECTIVE: To analyses the clinical results of transmyocardial laser
      revascularization (TMLR) for 77 patients with coronary artery diseases (CAD).
      METHODS: The mean age of the patients was (65 +/- 7) years. Previous medical
      record included CABG (6 patients), PTCA (9), AMI (66.2%), hypertension (70.1%),
      and diabetes mellitus (45.5%). TMLR was performed on the beating heart via a left
      anterolateral thoracotomy at the fifth intercostal space. Transesophageal
      echocardiography showed transmyocardial penetration of 23 +/- 6 channels.
      RESULTS: The hospital mortality was 3.8%, and postoperative complications were
      AMI (3.8%), left ventricular failure (2.6%), PVC (5.2%). After operation, the
      mean CCS angina class was improved from the baseline 3.5 +/- 0.7 to 2.1 +/- 0.3
      at 3 months, 1.7 +/- 0.3 at 6 months, 1.7 +/- 0.3 at 12 months and 1.8 +/- 0.4 at
      24 months. One patient died of AMI and two died not due to cardiac events during
      a follow-up of 3 to approximately 24 months. Echocardiography showed that the
      average of left ventricular ejection fractions was improved significantly at 6
      months after operation compared with the preoperative value (P = 0.0457). (201)TI
      SPECT showed a remarkable improvement in reversible ischemia in 70% patients
      followed up. Metabolic stress test for 20 patients followed up patients
      demonstrated an average increase in exercise tolerance from 7.1 +/- 3.2 min at
      the baseline to 9.6 +/- 1.3 min at 12 months (P = 0.021). Similarly the METs
      increased from 4.3 +/- 2.1 at the baseline to 5.4 +/- 2.0 at 12 months.
      CONCLUSIONS: TMLR is a safe and effective procedure for the treatment of end
      stage coronary artery diseases not amenable to PTCA or CABG. The effect of TMLR
      is associated with indication, correct evaluation of myocardial ischemia, and
      management for postoperative complications.

PMID- 11832135
TI  - [Perioperative changes of plasma ET-1 in patients undergoing coronary artery
      bypass grafting and the effect of nitroglycerin].
AB  - OBJECTIVE: To observe the dynamic changes of the plasma ET-1 and the effect of
      low dose nitroglycerin in patients with coronary artery bypass surgery. METHODS:
      40 patients with coronary artery bypass surgery were divided into group A and B.
      Group B received intravenous nitroglycerin 1 microg x kg(-1) x min(-1)
      perioperatively. We used RIA to assay the plasma ET-1 level. All the hemodynamic
      parameters were recorded by the Swan-Ganz catheter. RESULTS: The preoperative
      plasma ET-1 level in patients with coronary artery disease was significantly
      higher than the normal level. Five minutes after cardiopulmonary bypass in these
      patients the plasma ET-1 level was increased significantly until 6 to 8 hours
      after operation. The increased plasma ET-1 level in group B was less than in
      group A. There was a positive correlation between the plasma ET-1 level and the
      mean pulmonary pressure in group A 2 and 8 hours after operation. CONCLUSION: In
      patients undergoing coronary artery bypass surgery, the increased plasma ET-1
      level may be partly due to the influence of cardiopulmonary bypass. Low dose of
      nitroglycerin is beneficial to these patients.

PMID- 11832136
TI  - [Clinical and pathological characteristics of gastric stump cancer and recurrent
      gastric stump cancer].
AB  - OBJECTIVE: To study early diagnosis and rational treatment of gastric stump
      cancer and recurrent gastric stump cancer. METHODS: The data of 27 patients with
      gastric stump cancer and 23 patients with recurrent gastric stump cancer were
      analysed retrospectively during the past 20 years based on their clinical and
      pathological findings. RESULTS: The onset time was 10 years or more for gastric
      stump cancer and less than 10 years for recurrent gastric stump cancer after
      gastrectomy. Gastroscopy was better than double contrast radiography in
      diagnosis. Partial resection of gastric stump was performed for patients with
      early cancer at the anastomotic stoma of gastrojejunostomy. Total resection of
      gastric stump was made for other patients. Lymph node of the mesojejunum were
      dissected routinely because their metastasis rate was about 40.0% in patients
      with cancer of anastomotic stoma. The effect of surgical treatment was poor for
      patients with advanced cancer. CONCLUSIONS: Regular gastroscopy is useful in
      detecting gastric stump cancer in patients with gastric cancer after gastrectomy,
      or in those years after removal benign. Malignancy was more evident in recurrent
      gastric stump cancer than in primary gastric cancer. Prognosis is good for early
      stage cases and poor for late stage cases after surgical treatment.

PMID- 11832137
TI  - [Intraoperative endoscopic sphincterotomy for common bile duct stones during
      laparoscopic cholecystectomy].
AB  - OBJECTIVE: To assess the effects of approach-intraoperative endoscopic
      sphincterotomy (IOES) for common bile duct (CBD) stones during laparoscopic
      cholecystectomy (LC). METHODS: Twenty-seven patients with secondary CBD stones
      were treated by IOES during LC. Therapeutic effects were evaluated on the basis
      of the cure rate, early complications, and days of hospitalization. RESULTS: IOES
      was successfully performed in 26 (96.30%) of 27 cases, and their CBD stones were
      cleared completely. Two cases (7.69%) were complicated by mild acute
      pancreatitis. CONCLUSION: IOES as an alternative to the treatment of CBD stones
      during LC is safe and avoids reoperation.

PMID- 11832138
TI  - [Laparoscopic gastric resection].
AB  - OBJECTIVE: To modify laparoscopic surgery for gastric diseases. METHODS: From
      December 1992 to January 1999, 61 gastric laparoscopic operations were performed
      in our hospital. The age of the patients ranged from 29 to 78 years (mean 57.4).
      17 patients had Billroth II gastrectomy, 1 Billroth I gastrectomy, 2 proximal
      subtotal gastrectomy, 5 highly selective vagotomy, 3 gastrostomy, and 33
      resection of gastric submucosal benign tumor. 54 patients (88.5%) underwent
      complete laparoscopy, and 7 (11.5%) an assisted one RESULTS: The mean operative
      time was (164.2 +/- 93.5) min, the mean estimated blood loss was (218.3 +/-
      166.6) ml, and the mean hospital stay was (6.8 +/- 2.1) days. Flatus was present
      within 48 hours in 86% of the patients. Two patients had laparoscopic surgery for
      early gastric cancer, and were followed up for more than 55 months. Postoperative
      complication were noted in 2 patients, who were cured by reoperation and
      endoscopy therapy respectively. Only 4 patients required postoperative
      analgesics. CONCLUSION: Although specific indications need to be defined,
      laparoscopic surgery is feasible. But long-term follow-up should be made to
      evaluate its efficacy in treatment of gastric cancer.

PMID- 11832139
TI  - [MMF and CyA in the prevention of early acute rejection after renal
      transplantation].
AB  - OBJECTIVE: To investigate the effect of MMF and low dose CyA on the prevention of
      early acute rejection after renal transplantation. METHODS: 146 patients with
      kidney transplantation were analyzed retrospectively from December 1997 to
      January 1999. These patients were divided into two groups according to the
      immunosuppressive regimen: Aza group (78 patients) and MMF group (68 patients).
      All patients met the following criteria: HLA mismatch </= 3 loci, lymphocytes
      toxicity test < 10%, PRA < 20% for second or third transplantation, warm ischemia
      time 5-11 minutes, and cold ischemia time 3-24 hours. RESULTS: There were 24
      patients with acute rejection episodes (30.77%) in the Aza group; and 10 patients
      (14.71%) in the MMF group, (P < 0.05). The dosage of CyA and blood concentration
      of CyA were significantly different; 6.00 +/- 1.21 mg x kg(-1) x d(-1) and 286.00
      +/- 20.02 microg/L in the Aza group; 4.00 +/- 1.14 mg x kg(-1) x d(-1) and 204.00
      +/- 20.18 microg/L in the MMF group (P < 0.001). CONCLUSIONS: MMF with low dose
      CyA based triple regimen could prevent the acute rejection episodes effectively
      at the early period of post transplantation. This triple regimen can reduce the
      acute rejection episodes by 50%. To some extent, low dose CyA may avoid
      nephrotoxicity. The long-term effect of this regimen on allograft is still needed
      to observe.

PMID- 11832140
TI  - [Anisodamine in prevention and treatment of sepsis of severely burned patients].
AB  - OBJECTIVE: To observe the preventive effect of anisodamine on possible sepsis of
      patients with major burns and the effect of anisodamine on patients with sepsis.
      METHODS: Forty-two patients with extensive burn admitted to our burn institute
      from April 1998 to November 1999 were divided randomly into two groups: treatment
      group (T group) and control group (C group). In the T group, all 20 patients
      received fluid resuscitation regimen with anisodamine, and in the C group, 22
      patients received the regimen with no anisodamine. A tonometry catheter was
      positioned in the stomach, connecting with the automatic gas analysis machine
      (Datex-Engstrom Corporation, Dutch) for determining gastric intramucosal pH
      (pHi). The plasma concentrations of diamine oxidase (DAO) and endotoxin were
      measured. Correlation analysis between pHi, DAO and endotoxin were made
      respectively during early stage of postburn. All the parameters in 7 patients
      with sepsis before and after administration of anisodamine were compared with
      those in 6 patients with sepsis without use of anisodamine. RESULTS: The
      incidence of sepsis in the T group was lower (20.0%) than that in C group
      (40.9%). The gastric pHi value in the early period of postburn was significantly
      higher in the T group than in the C group (P < 0.05). Concurrently, the plasma
      concentrations of DAO and endotoxin were significantly lower in the T group than
      in the C group (P < 0.05 or 0.01). A significant negative correlation was seen
      between the gastric pHi and respective values of DAO, endotoxin (P < 0.05 or
      0.01). There were a decrease in gastric pHi, and an increase in plasma DAO and
      endotoxin level in patients with septic episode; however all the parameters after
      administration of anisodamine were improved compared with those in septic
      patients without use of anisodamine. CONCLUSIONS: Intestinal ischemic injury
      plays an important role in provoking sepsis during early postburn period.
      Anisodamine is effective in restoring intestinal circulation both in the shock
      phase and after the development of sepsis.

PMID- 11832141
TI  - [Allotransplantation of cultured fetal parathyroid gland cells in treating
      patients with hypoparathyroidism].
AB  - OBJECTIVE: To evaluate the therapeutic efficacy of transplantation of cultured
      human fetal parathyroid gland (chf-PTG) cells in treating patients with primary
      or secondary hypoparathyroidism. METHODS: Chf-PTG cells were allotransplanted
      into the renal adipose capsules of 6 patients with hypoparathyroidism under the
      ultrasonic guidance. The levels of serum parathyroid hormone (PTH) and calcium
      were monitored by radioimmunometric assay (RIA) and biochemical method,
      respectively. Both indexes of pre-and post-operation were compared and the data
      were analyzed. RESULTS: The levels of serum PTH and calcium were markedly
      elevated from three days to the first two weeks following transplantation of chf
      PTG cells (P < 0.01). The PTH and calcium levels gradually stabilized from day 14
      up to months 9-12, during which the symptoms of the patients alleviated or
      relieved. CONCLUSION: The transplantation of chf-PTG cells is a potential method
      for treating patients with primary or secondary hypoparathyroidism.

PMID- 11832143
TI  - [Telomerase activity and cellular apoptosis of bladder cancers].
AB  - OBJECTIVE: To explore the relationship between clinicobiological acting,
      telomerase activity and cellular apoptosis of bladder cancer. METHODS: The
      intensity of telomerase activity and cellular apoptosis of bladder cancer were
      detected by telomeric repeat amplification protocol (TRAP) and terminal
      deoxynucleotidyl-transferase mediated dUTP-biotin nick end labeling (TUNEL) assay
      respectively. RESULTS: The positive rate of telomerase activity of bladder cancer
      was 89.29% and the apoptosis index of bladder cancer was (45.16 +/- 14.43)%. The
      intensity of telomerase activity and apoptosis index of bladder cancer were not
      related to patient's age, sex, size or number of tumor (P > 0.05), but to the
      "grade", "stage" and prognosis of bladder cancer (P < 0.01). The higher the
      intensity of telomerase activity or less cellular apoptosis, the poor prognosis
      of differentiated or more advanced bladder cancer. The intensity of telomerase
      activity was negatively correlated with cellular apoptosis of bladder cancer (r =
      -0.69, P < 0.01). CONCLUSIONS: The intensity of telomerase activity and cellular
      apoptosis are correlated with the grade, stage and prognosis of bladder cancer.
      The detection of telomerase activity and cellular apoptosis are helpful in
      clinical analysis and evaluation of prognosis of bladder cancer.

PMID- 11832142
TI  - [Melanoma antigen-3 expression in human hepatocellular carcinoma].
AB  - OBJECTIVE: To investigate the expression of melanoma antigen-3 (MAGE-3) mRNA in
      human hepatocellular carcinoma (HCC) and probe into the theoretical feasibility
      that MAGE-3 antigens can be developed as a new peptide vaccine for immunotherapy
      in HCC patients. METHODS: The expression of MAGE-3 mRNA in HCC tissues and the
      adjacent non-HCC liver tissues was studied using RT-PCR in 45 HCC patients. The
      results were compared with those of 16 cirrhotic patients and 12 patients whose
      liver tissues were pathologically normal. MAGE-3 mRNA positive PCR products were
      DNA sequenced in 3 HCC patients. The sequenced fragments of MAGE-3 cDNA were used
      as template by which a [alpha(32)P] labeled probe was synthesized and employed
      for Southern blot analysis. HLA class I-A and -B typing of 43 HCC patients were
      assayed by ELISA. RESULTS: Of the 45 HCC samples, 35 (78%) expressed MAGE-3 mRNA
      and six HCC adjacent tissues were also positive in MAGE-3 expression.
      Pathological examination showed cellular heteromorphism in these adjacent
      tissues. The non-HCC liver tissues from cirrhosis and normal liver samples were
      not MAGE-3 mRNA detectable. The DNA sequence confirmed that the target gene
      fragment in all of the 3 samples of PCR products was MAGE-3 cDNA. Southern
      blotting result confirmed that of RT-PCR assay. In HCC patients, the predominant
      types of HLA were A(2) (53.5%), A(11) (25.6%), A(24) (20.9%), A(33) (20.9%),
      B(13) (28.3%), and B(35) (23.2%). MAGE-3 mRNA expression in HCC showed no
      correlation with the level of serum AFP and the size of the tumor. CONCLUSIONS:
      MAGE-3 mRNA is expressed at a high percentage of HCC samples. This tumor
      rejection antigen may be used as peptide vaccine for immunotherapy of HCC
      patients. The phenomena that some non-HCC adjacent tissues with heteromorphism
      can express MAGE-3 like their paired HCC tissues indicate that the expression of
      MAGE-3 may be an indicator in the early stage of carcinogenesis of liver tissues.

PMID- 11832145
TI  - [Regulating effects of transforming growth factor-beta (TGF-beta) on gene
      expression of collagen type II in human intervertebral discs].
AB  - OBJECTIVE: To assess the regulating effects of TGF-beta on gene expression of
      collagen type II in the human intervertebral discs. METHODS: In situ
      hybridization was used to investigate the effect of TGF-beta1 on collagen mRNA in
      confluent primary and passaged monolayer cell cultures of annulus fibrosus (AF)
      as well as nucleus pulposus (NP). The mean photodensitometry of cell smears as
      semi-quantitative analysis was evaluated by VIDAS software. RESULTS: In primary
      cultures, 1 ng/ml and 10 ng/ml TGF-beta1 inhibited the collagen type II mRNA
      levels by 74.6% and 60.2% respectively in AF; they also inhibited the mRNA levels
      by 69.6% and 55.5% respectively in NP. In passaged cultures in which the
      notochordal cells and chondrocytes were in dedifferentiation status, 1 ng/ml and
      10 ng/ml TGF-beta1 increased the collagen type II mRNA levels by 151% and 166%
      respectively in AF and also increased the mRNA levels by 145% and 198%
      respectively in NP. CONCLUSIONS: The regulation effect of TGF-beta on collagen
      type II gene expression is dependent on whether the cells are fully
      differentiated or undergoing phenotype loss, and TGF-beta may play an important
      role in the repair process during early disc degeneration, especially in nucleus
      pulposus.

PMID- 11832144
TI  - [Hemodynamic and pathologic changes in open abdominal wound after seawater
      immersion in dog].
AB  - OBJECTIVE: To study the experimental basis for the treatment to the sick and
      wounded with abdominal open wound in land warfare and naval battle. METHODS:
      Animal model was made with adult dogs to observe the changes of mean artery
      pressure (MAP), pulmonary capillary wedge pressure (PCWP), central vein pressure
      (CVP), cardiac output (CO), cardiac index (CI) and pathologic changes of heart,
      pulmonary, hepatic, nephritic, intestinal, and gastric tissues under the optical
      and electrical microscope. RESULTS: Comparing with simple open abdominal, the
      hemodynamic disorder in open wound after seawater immersion was more serious;
      with a higher death rate. CONCLUSIONS: There was differences in hemodynamic and
      pathologic changes in seawater immersion wound and general wound. The body
      damaged is seriously when open abdominal wound immersed in seawater. Special
      measure must be taken in treating open abdominal wound after seawater immersion.

PMID- 11832146
TI  - [Mitogenesis of platelet-derived growth factors to human osteoblasts modulated by
      basic fibroblast growth factor].
AB  - OBJECTIVES: To investigate the mechanism by which basic fibroblast growth factor
      modulates the mitogenesis of platelet-derived growth factor to human osteoblasts.
      METHODS: The osteoblasts isolated from human fetal calvaria were incubated with
      PDGF-AB (100 ng/ml) or bFGF(10 ng/ml) combined with PDGF-AB (100 ng/ml); the
      growth curve was plotted. The(3)H-TdR incorporation of the osteoblasts was
      measured after the cells were incubated with different combination of bFGF and
      PDGF-AA or PDGF-BB. After incubated with bFGF (10 ng/ml) for 24 hours, the number
      of PDGFR-alpha and PDGFR-beta on the membrane of the osteoblasts was detected by
      fluoroimmunoassay. RESULTS: Four days after PDGF-AB added into the medium, the
      population of the osteoblasts was larger than that of the control (P < 0.05). The
      number of the osteoblasts incubated with PDGF-AB (12.1 x 10(4)) was 1.8 times as
      large as the control (6.8 x 10(4)) in the 10th day (P < 0.05), and that of the
      osteoblasts incubated with both bFGF and PDGF-AB increased more quickly than the
      cells only incubated with PDGF-AB. The incorporation of (3)H-TdR into the
      osteoblasts cultured with bFGF combined with PDGF-AA (533.6 +/- 13.1) was more
      than that cultured only with PDGF-AA (435.4 +/- 14.8, P < 0.01), so was the
      incorporation of (3)H-TdR of those cells cultured with bFGF and then PDGF-AA
      (633.8 +/- 51.5). bFGF up-regulated PDGFR-alpha and down-regulated PDGFR-beta on
      the surface of the human osteoblasts. CONCLUSION: bFGF elevates the mitogenesis
      of PDGF-AA or -AB to human osteoblasts by up-regulating PDGFR-alpha.

PMID- 11832147
TI  - [The effect of V-shaped nitinol alloy implantation on acetabular dysplasia: an
      experimental study].
AB  - OBJECTIVE: To observe the effect of V-shaped nitinol alloy implantation into the
      acetabular roof of puppies with acetabular dysplasia on acetabular dysplasia.
      METHODS: The puppies with acetabular dysplasia were divided randomly into two
      groups. Osteotomy was begun about 0.5 cm above the acetabulum, using a curved
      osteotome this cut must proceed between the medial wall of the ilium and medial
      wall of the acetabulum. The osteotomy does not have to be carried to the
      triradiate cartilage. When the osteotomy is completed, the superior aspect of the
      acetabulum can be hinged downward by curved osteotome. The V-shaped nitinol alloy
      was wedged securely in the osteotomy site. Roentgenogram was made 4 and 12 weeks
      after operation in all animals. RESULTS: The inclination of the acetabular roof
      was redirected and the acetabular index was decreased. Microscopic study showed a
      marked proliferation of cartilaginous cells of the acetabular cartilage.
      CONCLUSION: The V-shaped nitinol alloy implantation into the acetabular roof can
      correct the sloping acetabular roof, increase the coverage on the femoral head,
      and improve the growth of the acetabulum.

PMID- 11832148
TI  - Lymph node metastasis of T1, T2 squamous carcinoma and adenocarcinoma of lung:
      characteristics and clinical significance.
AB  - OBJECTIVES: To investigate the frequency, distribution and features of lymph
      nodes metastasis in T(1)/T(2) squamous carcinoma and adenocarcinoma of lung, and
      to provide evidence for extensive dissection of lymph nodes. METHODS: 254
      patients with T(1)/T(2) squamous carcinoma and adenocarcinoma of lung underwent
      R2 surgery plus extensive dissection of hilar, interlobular and mediastinal lymph
      nodes according to the grouping system proposed by Naruke. RESULTS: A total of 1
      685 groups of lymph nodes were dissected. The metastatic rates of N(1) and N(2)
      were 20.0% and 10.2%. The difference was very significant between T(1) and T(2)
      (P < 0.01). No, N(2) metastasis was found in T(1) squamous carcinoma. N(2)
      metastatic rates were 22.0% in squamous carcinoma and 40.9% in adenocarcinoma (P
      < 0.01). 64.3% of squamous carcinomas spread to only one group of N(2) nodes, and
      over 3 groups of lymph nodes were positive in 46.2% of adenocarcinomas. Saltatory
      metastasis accounted for 57.5% of N(2) metastasis. 13.6% of N(2)-positive tumors
      in the upper lobes metastasized to the lower mediastinum, whereas 51.6% of N(2)
      positive tumors in the lower lobes spread to the upper mediastinum. CONCLUSIONS:
      The frequency of lymph node metastasis increases with the growth of tumors.
      Metastasis occurs more frequently in adenocarcinoma than in squamous carcinoma.
      Tumor at any site can metastasize to the distant mediastinum. Except for T(1)
      squamous carcinoma, radical surgery can be achieved only by extensive dissection
      of ipsilateral intrapulmonary and mediastinal lymph nodes.

PMID- 11832149
TI  - [Operative treatment of displaced proximal humeral fractures: follow-up and
      analysis of 31 patients'].
AB  - OBJECTIVE: To study the methods and the results of operative treatment of
      displaced proximal humeral fractures. METHODS: We reviewed thirty-one patients
      who had been diagnosed as having displaced proximal humeral fractures and had
      been operated on from July 1989 to December. 1998 in our hospital. The mean
      follow-up time was 40.5 months (8 - 124 months). Their age ranged from 15 to 62
      years (average, 36.8 years); 18 patients were male and 13 female. Neer fracture
      classification system and rating system were used. In all patients, delto
      pectoral approach was adopted. Twelve fractures were fixed with plates, fifteen
      fractures with screws, and four fractures with Kirschner wire and plaster.
      RESULTS: Of two-part surgical neck fractures, nine of thirteen patients (69%)
      were excellent or good with no necrosis and un-union. In three-part or four-part
      fractures, the rate of satisfaction with open reduction and internal fixation
      (ORIF) was rather lower. In three-part fractures, the rate of humeral head
      necrosis was 44%, and in four-part fractures, over 75%. CONCLUSIONS: In two-part
      and three-part fractures, ORIF is a better treatment, but care should be taken to
      avoid using plates. As for classic four-part fractures, the rate of satisfaction
      with ORIF is poor and the rate of necrosis is higher.

PMID- 11832150
TI  - [Treatment of humeral shaft nonunion with interlocking nail and percutaneous
      injection of bone marrow].
AB  - OBJECTIVE: To investigate the effect of treatment of humeral shaft nonunion with
      interlocking nail and percutaneous injection of bone marrow after operation.
      METHODS: Twenty-five adult patients with humeral shaft nonunion, initially
      treated with plates, intramedullary nails, or external fixators changed to use
      RussellTaylor reamed antegrade intramedullary nails with autologous bone grafting
      and percutaneously bone marrow injection into the fracture sites ten days after
      the operation to promote union. RESULTS: All patients achieved a solid union with
      good function. The union period was a median of 4.5 months. CONCLUSION: We
      believe that the procedure may provide firm internal fixation and improve
      activity of osteoblasts in fracture sites for accelerating fracture healing.

PMID- 11832151
TI  - [Does simple posterior dislocation of the elbow necessitate strict
      immobilization?].
AB  - OBJECTIVE: To research for the ideal treatment of isolated posterior dislocation
      with the elbow after reduction. METHODS: 36 patients of isolated posterior
      dislocation of the elbow after closed reduction (male 26, female 10; left 14,
      right 22; dominant extremity 21, undominant extremity 15; average age 22) were
      examined by varus and valgus stress test and push-draw test. Satisfactory
      stability from 30 degrees to 130 degrees flexion of the elbow was found in all
      patients. For the 30 patients below 35 years old, long-arm posterior splint was
      applied to immobilize the elbow joint at 90 degrees flexion and pronation for one
      week. For 6 patients over 35 years old, we only immobilized the elbow joint for 3
      to 5 days with a neck-wrist sling. Prompt active motion begin after the swelling
      and pain reduced slightly, but the last 30 extension was not allowed for the
      first 1 to 2 weeks. Forceful passive motion and stretching of the elbow joint
      were avoided in all patients. RESULTS: The average follow-up time was 9 months (3
      - 15 months). Range of motion and muscle power were regained within 3 - 4 months.
      32 patients rehabilitated completely and 4 of the 6 patients decreased extension
      for 5 degrees - 10 degrees. No unstable symptoms and signs or recurrent
      dislocation were found. No ectopic calcification or post-traumatic arthritic
      changes were found on X-ray follow-up. CONCLUSIONS: The ulna-humeral joint is one
      of the most highly constrained joints in the body with intrinsic stability. Bony
      structure is stable enough to allow for capsular and ligamental structure
      healing, even during active motion. For isolated posterior dislocation of the
      elbow joint, short-term immobilization and early functional exercise are
      desirable. Elbow instability and recurrent dislocation are rare and do not
      necessitate long-term strict immobilization.

PMID- 11832152
TI  - [The mechanism of biological adaptability of peripheral nerves during limb
      lengthening in rabbits].
AB  - OBJECTIVE: To study the mechanism of subclinical damage and repairing process of
      peripheral nerves during gradual tibial lengthening. METHODS: Histological
      investigation, electrophysiological examination of tibial nerve and GAP-43 mRNA
      expression of sciatic nerve related spinal cord and ganglion were observed in
      10%, 20%, 30%, 40% lengthening, and at 2, 4, 8 weeks phases after 40% limb
      lengthening in 80 rabbits. RESULTS: With the increase of elongation, severer and
      more obvious nerve damage and stronger expression of GAP-43 mRNA happened.
      However, nerve regeneration occurred synchronously and the changes recovered
      gradually within 8 weeks. CONCLUSION: Damage of the peripheral nerves is common
      during limb lengthening. But, it is temporary and recoverable in case the
      lengthening rate is < 1 mm/d.

PMID- 11832153
TI  - [The treatment of premature arrest of growth plate with a novel engineered growth
      plate: experimental studies].
AB  - OBJECTIVES: To observe the role of the engineered growth plate (EGP) in the
      treatment of premature arrest of growth plate and to establish a novel treatment
      method for the premature arrest of the growth plate. METHODS: The engineered
      growth plates were cultured for the first time by using polylactic acid (PLA) as
      cell scaffold seeded with growth plate chondrocytes and they were implanted into
      the medial proximal defects of growth plates of New Zealand rabbit tibia. The
      degree of deformity of the tibia was evaluated by X-ray and the expression of
      collagen II mRNA of regenerating growth plate was detected by in situ
      hybridization technique. RESULTS: Little deformity appeared in the EGP group 8
      weeks after operation. Some deformity was seen in the EGP group 16 weeks after
      operation, whereas it's degree was much less than that of the control group (P =
      0.0001). The degree of the angular deformity of the EGP precultured with bFGF and
      TGF-beta group was less than that of the EGP group (P < 0.05). The cells in the
      regenerating growth plate arranged in column and were stained blue by in situ
      hybridization technique. CONCLUSION: The EGP can prevent the formation of bony
      bridge and restore the growth of the damaged growth plate.

PMID- 11832154
TI  - [Reconstruction of hip, knee, and ankle bony fused in non-functional position  of
      ankylosing spondylitis patients].
AB  - OBJECTIVE: To evaluate the reconstruction of hip, knee and ankle joints with bony
      fusion at non-functional positions for patients with severe late-stage ankylosing
      spondylitis (AS). METHODS: From January 1996 to May 1997, simultaneous
      ipsilateral total hip, knee and ankle replacement was performed under single
      anesthesia on 2 patients (3 sides) with multiple joint deformity including bony
      fusion at non-functional positions. They were followed for 29 months on average.
      RESULTS: Satisfactory range of motion and function were observed. HSS knee score
      on average was improved by 45 points and Harris hip score by 37.7 points. There
      were no wound healing problems or late infection. No aseptic loosening was found.
      CONCLUSIONS: Simultaneous ipsilateral total hip, knee and ankle replacement not
      only reduced cost for hospitalization, but also facilitated early rehabilitation.
      To our knowledge, this is the first report on this type of surgery, named
      ipsilateral tri-arthroplasty.

PMID- 11832155
TI  - [Lymph node metastasis and the extent of lymph node dissection for gastric
      cancer: report of 326 cases].
AB  - OBJECTIVE: To investigate the pattern of lymph node metastasis and the extent of
      lymph node dissection for gastric cancer. METHODS: 326 patients with gastric
      cancer admitted from 1990 to 1999 were analyzed retrospectively after D(2), D(3)
      or D(3) plus para-aortic lymphadenectomy (D(3) + PAL). RESULTS: The total
      incidence of lymph node metastasis was 69.9%; node involvement was 15.4% and
      77.4% respectively for early gastric cancer and advanced gastric cancer. Depth of
      invasion, tumor size and histology affected lymph node metastasis significantly
      (P < 0.05). For T(1) patients, node involvement was mainly confined to N(1) and
      one patient had N(2) metastasis; 8.1% of T(2) patients and 28.7% of T(3), T(4)
      patients had N(3), M(1) lymph node metastasis. Among 107 patients who received
      D(3) + PAL, 16a2b1 lymph node metastasis was found in 15.0%. The patients who had
      16a2b1 node involvement were all suffered from advanced gastric cancer and N(1)
      N(2) node metastasis. In the patients with serosal invasion-positive tumors or
      tumors size over 5 cm, the incidence of 16a2b1 metastasis was high, and that of
      entire stomach cancer was up to 38.5%. The 3-year and 5-year survival rates for
      D(3) + PAL group were 60.7% and 50.0% respectively. After D(3) + PAL, the 1-and 2
      year survival rate, of patients with 16a2b1 metastasis were 60.0%, 50.0%
      respectively. CONCLUSIONS: D(2) lymphadenectomy should be taken for patients with
      early gastric cancer and D(3) lymphadenectomy for those with relatively early'
      advanced gastric cancer. For advanced gastric cancer with suspect or confirmed
      N(1)-N(2) node metastasis, tumor size over 5 cm and/or serosa invasion, D(3) plus
      para-aortic lymphadenectomy appears to be a necessary surgical procedure.

PMID- 11832156
TI  - [The effect of methylenum coeruleum in laparoscope cholecystectomy].
AB  - OBJECTIVES: To help the operator correctly judge in operation the cystic gall
      duct and choledoch, and eliminate the operation wound. METHODS: To divide
      laparoscope cholecystectomy patients with the same weight at the same period into
      two groups: development group (589 cases) using methylenum coeruleum and
      conducting cholecysto-puncture visualization during the operation in which colors
      of cholecyst, cystic gall duct and choledoch turn blue; comparative group (553
      cases) using regular laparoscope cholecystectomy. RESULTS: The two groups
      differed remarkably in operation time, complication, and transferring rate (P <
      0.01). CONCLUSIONS: Methylenum coeruleum development technology in operation is a
      kind of visualization to help the operator judge in operation Calot triangular
      anatomy construction correctly, reduce the operation time obviously, and increase
      the rate of success.

PMID- 11832157
TI  - [Benign tumor of duodenum: report of 8 cases].
AB  - OBJECTIVE: To investigate the problems of diagnosis and treatment in patients
      with benign tumor of duodenum. METHOD: Clinico pathological data of 8 patients
      with benign tumors of duodenum treated surgically in our department from 1989 to
      2000 were analyzed retrospectively. RESULTS: Of the 8 patients, 3 had a Brunner's
      grand adenoma, 2 leiomyoma, 2 mesenchymoma, and 1 lipoma. In general, the
      patients were asymptomatic and the lesions were discovered incidentally.
      Gastrointestinal bleeding might be the main symptom even if it was nonspecific.
      Bleeding might be melena or hematemesis and the patients might develop signs of
      anemia. Upper gastrointestinal tract examination and gastroduodenoscopy was
      performed before operation in 7 patients. The tumor was removed through
      longitudinal incision during duodenotomy. CONCLUSIONS: Gastrointestinal bleeding
      is common in patients with benign tumor of duodenum. The upper gastrointestinal
      tract examination and gastroduodenoscopy are major methods for diagnosis. The
      best treatment of choice is local resection.

PMID- 11832158
TI  - [Primary non-specific ureteritis].
AB  - OBJECTIVE: To better understand primary non-specific ureteritis. METHODS: The
      etiological, clinical, and pathological manifestations, diagnosis, and treatment
      of 3 cases of primary non-specific ureteritis were discussed. RESULTS:
      Preoperative diagnosis failed. Uretero-ureterostomy was performed in 2 cases, and
      ureteroneocystostomy in one. The patients were free from hydronephrosis and
      ureteral dilatation. CONCLUSIONS: Diagnosis depends on pathological
      manifestations, differentiation from secondary non-specific ureteritis, ureteral
      tuberculosis, negative X-ray of ureteral stone and ureteral carcinoma. Surgical
      intervention is effective with good prognosis.

PMID- 11832159
TI  - [Surgical approaches of pheochromocytoma].
AB  - OBJECTIVE: To evaluate the effects of surgery of Pheo. METHODS: Pheochromocytoma
      was removed in 89 patients. RESULTS: In 39 patients, pheochromocytoma was removed
      by intercostal incision at the 11th rib and 15 at the 10th rib, 14 by transrectal
      incision, 9 by abdominothoracic incision, 5 by abdominal subcostal oblique
      incision, 3 by inferior abdominal incision, 3 by posterolateral incision. One
      patient received laparoscopic surgery. CONCLUSIONS: Pheochromocytoma definitely
      localized was removed by intercostal incision at the 10th or 11th rib. The
      suitable pathway for removal giant pheochromocytoma or pheochromocytoma related
      big vessels is transrectal incision or abdominothoracic incision. The incision of
      multiple pheochromocytoma or extra-adrenal pheochromocytoma may be in the middle
      of the abdomen.

PMID- 11832160
TI  - [Detection of K-ras gene mutations in DNA extracted from the plasma of patients
      with pancreatic cancer].
AB  - OBJECTIVES: To detect mutations of the K-ras codon 12 in DNA extracted from the
      plasma of patients with pancreatic cancer, and to explore the possibility of
      using this method in early diagnosis of pancreatic cancer. METHODS: Plasma DNA
      was isolated from the blood of 22 patients with pancreatic cancer and from 20
      normal controls. K-ras codon 12 mutations were detected by mutant enriched
      polymerase chain reaction-restriction fragment length polymorphism technique and
      subsequent product sequencing. The relation of K-ras mutations in plasma to
      clinical features in pancreatic cancer patients was analyzed. RESULTS: Seventeen
      (77.3%) of 22 patients with pancreatic cancer had a codon 12 K-ras mutation in
      their plasma DNA. In two patients, the PCR products were sequenced and the
      mutations were confirmed. The occurrence of K-ras mutations in the plasma DNA was
      not related to tumor location, tumor size, and TNM stage. No K-ras mutation was
      detected in the plasma specimen of any of the normal controls. CONCLUSIONS: K-ras
      mutations are frequently found in the plasma DNA of patients with pancreatic
      cancer. Analysis of K-ras mutation in the plasma DNA may be useful in the early
      detection of pancreatic cancer.

PMID- 11832161
TI  - [Prognostic factors of clinical curative effect for malignant obstructive
      jaundice].
AB  - OBJECTIVE: To explore prognostic factors for clinical treatment of patients with
      malignant obstructive jaundice. METHODS: 17 variables from 216 consecutive
      patients with malignant obstructive jaundice admitted from 1990 to 1997 were
      included for statistical analysis. RESULTS: The overall mortality was 19.9%
      (43/216), and the morbidity 37.5% (81/216). The morbidity of radical operation
      was higher than that of palliative operation (P < 0.01). There was a highly
      significant correlation between mortality, morbidity, ASA grade and duration of
      jaundice (P < 0.01). No correlation was seen between the mortality, type of
      operation and cause of jaundice. There was a highly significant correlation
      between the morbidity and the type of operation. CONCLUSIONS: The choice of
      operation in patients with malignant obstructive jaundice is radical operation.
      Early diagnosis and choice of treatment are essential to improving carative
      effect.

PMID- 11832163
TI  - [Changes of leukocyte rheologic characteristics and cell adhesion molecules in
      patients with multiple organ failure after severe trauma].
AB  - OBJECTIVE: To explore the changes of leukocyte rheologic characteristics and of
      cell adhesion molecule in patients with multiple organ failure (MOF) after severe
      trauma. METHODS: By using the erythrocyte deformability apparatus, platelet and
      thrombus adhesion dual-purpose apparatus and enzyme-linked immunosorbent assay
      (ELISA), We measured the leukocyte deformability (LD), leukocyte adhesion
      function (LAF), leukocyte CD18 expression, soluble intercellular adhesion
      molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule (sVCAM-1)
      concentration in 36 MOF patients, 31 trauma patients, and 35 to be controls.
      RESULTS: The leukocyte filtration index (LFI), leukocyte adhesion rate (LAR),
      leukocyte CD18 expression, and sICAM-1 and sVCAM-1 concentration were
      significantly higher in MOF patients than in controls and trauma patients (F =
      68.45 - 116.20, q = 12.161 - 21.374, P < 0.00), and the changes of these
      indicators in MOF deaths were more obvious than those in MOF survivors (t = 6.920
      - 11. 665, P < 0.00). The LFI and LAR in MOF patients were positively related to
      leukocyte CD18 expression, sICAM-1, and sVCAM-1 concentration (r = 0.691 - 0.844,
      P < 0.001); LFI was positively related to LAR (r = 0.711, P < 0.001). CONCLUSION:
      The abnormalities of leukocyte rheologic characteristics and CAMs might be
      closely related to the occurrence of MOF and the severity of pathologic changes.

PMID- 11832162
TI  - [Expression and significance of MMP2 and type IV collagen in gastric cancer].
AB  - OBJECTIVE: To evaluate the relationship between the expression of MMP(2), type IV
      collagen, and invasion and metastasis of gastric cancer. METHODS: The expression
      of MMP(2) and Type IV collagen was observed by using immunohistochemistry
      technique. RESULTS: The MMP(2) expression clearly appeared in the poor
      differentiated adenocarcinoma and tubular adenocarcinoma (85.7%, 77.7%). Type IV
      collagen destruction was observed simultaneously. MMP(2) was highly expressed in
      patients with cancer embolus in blood vessel and lymphatic vessel or with lymph
      node metastasis (83.3%, 86.7%). CONCLUSIONS: The high expression of MMP(2) was
      significantly associated with infiltration and metastasis of gastric cancer. The
      extracellular matrix, especially type IV collagen was destroyed in the cases of
      high expression of MMP(2). These results suggest that monitoring the level of
      MMP(2) expression may be an index for evaluation of prognosis.

PMID- 11832164
TI  - [Expression of thymidylate synthase gene and recurrence of colorectal carcinoma:
      their relation and clinical significance].
AB  - OBJECTIVE: To study the relationship between expression of thymidylate synthase
      (TS) gene and recurrence of colorectal carcinoma and its effect on clinical
      treatment. METHODS: RT-PCR was used to detect the expression of TS gene in
      primary foci, para-tumoral intestine mucosa, local recurrence, abdominal-pelvic
      dissemination and hepatic metastasis in 68 cases of colorectal carcinoma, and TS
      protein was examined with western blot. RESULTS: In 68 cases of colorectal
      carcinoma, the expression of TS gene in primary foci was 22.1% (15/68); and the
      positive rates of TS gene expression in local recurrence, abdominal-pelvic
      dissemination and hepatic metastasis were 88.5% (23/26), 85.0% (17/20), 40.9%
      (9/20) respectively. The rates of TS protein expression in primary foci, local
      recurrence, abdominal-pelvic dissemination and hepatic metastasis were 22.1%
      (15/68), 84.6% (22/26), 80.0% (16/20), 36.4% (8/22) respectively. The negative
      expression of TS gene and TS protein was detected in paratumoral intestinal
      mucosa. The results of TS gene and TS protein expression were identical with
      those the two methods. The positive rates of TS gene and TS protein expression in
      diversified recurrence foci and metastasis were higher than those in primary foci
      (P < 0.01). The differences of TS gene and TS protein expression rates between
      recurrence and hepatic metastasis were significant (P < 0.01). The expression
      rates of TS gene and TS protein in local recurrence and abdominal-pelvic
      dissemination tissues were higher than those in hepatic metastasis. CONCLUSION:
      Overexpression of TS gene plays an important role in the process of local
      recurrence and abdominal-pelvic dissemination of colorectal carcinoma.

PMID- 11832165
TI  - [Sentinel lymph node biopsy in breast cancer: value for predicting the status of
      axillary node].
AB  - OBJECTIVE: To evaluate feasibility and accuracy of intraoperative lymphatic
      mapping with sentinel lymphadenectomy (SLND) for predicting axillary status in
      patients with breast cancer. METHODS: Our study enrolled 52 patients with primary
      breast cancer, clinically and ultrasonographically negative axillae. Mapping
      procedures and SLND were performed using methylene blue injected at the primary
      breast cancer site followed by axillary lymph node dissection (ALND). Sentinel
      node (SN) was examined by using frozen sections intraoperatively and all of the
      axillary lymph nodes were evaluated pathologically (HE) after operation. RESULTS:
      Sentinel nodes were identified in 46 (88.5%) of 52 procedures and nodal status
      accurately predicted axillary in 44 (95.7%) of 46 cases. In 2 (4.3%) of 46 cases,
      the SN was false-negative. The overall sensitivity of the SN technique was 90.9%,
      with a specificity of 100%. The overall positive and negative predictive values
      were 100% and 92.3%, respectively. In 15 (75%) of 20 cases of clinically
      negatively and pathologically positive axillary, the SN was the only tumor
      involved lymph node identified. CONCLUSION: Our study indicates that
      intraoperative lymphatic mapping using a vital dye and SLND can accurately
      predict the axillary status of primary breast cancer patients with clinically and
      ultrasonographically negative axillae.

PMID- 11832166
TI  - [The effect of splenectomy on circulating endotoxin clearance and tissue
      distribution of endotoxin in rats].
AB  - OBJECTIVE: To study the effect of splenectomy on circulating endotoxin clearance
      and tissue distribution of endotoxin, and investigate the potential mechanism(s)
      underlying inflammatory response and multiple organ damage following splenectomy.
      METHODS: 112 male Wistar rats were randomly divided into two groups: control
      group (n = 56, included omentectomy and mobilization of the spleen), and
      splenectomy group (n = 56). The latter was further sub divided into 10-min, 0.5-,
      1.5-, 4-, 12-, 24-hour groups after endotoxin challenge. Tissue and systemic
      blood endotoxin concentrations were measured using the chromogenic limulus
      amebocyte lysate (LAL), which was modified by perchloric acid (PCA) pretreatment
      for samples. Liver function parameter and lung tissue myeloperoxidase (MPO) were
      also measured. RESULTS: After endotoxin administration, plasma endotoxin
      concentrations were higher in splenectomized rats than in controls at 10 minutes
      and 0.5 hour (P < 0.01). Endotoxin clearance was delayed in liver and lung in
      animals after splenectomy. MPO values of the control group were significantly
      higher than those of splenectomy groups (P < 0.01). CONCLUSION: Splenectomy can
      lead to impairment of intravascular clearance of endotoxin and endotoxin
      accumulation in liver and lung. Endotoxin accumulated in local sites may be
      involved in the development of inflammatory response and multiple organ
      dysfunction following splenectomy.

PMID- 11832167
TI  - [Clinical use of acellular allogenic dermis or acellular porcine dermis with
      split-thickness autologous skin graft in 119 cases].
AB  - OBJECTIVE: To observe the effect of acellular allogenic dermis or acellular
      porcine dermis together with split-thickness autologous skin graft on coverage of
      deep burn wound and the wound of scar excision. METHODS: Acellular allogenic
      dermis or acellular porcine dermis produced by our unit, with split-thickness
      autologous skin graft, were used in repairing various wounds in 119 cases. The
      take rate of various wounds was compared, and the take rate of wounds in which
      autologous skin from different sites was used to cover either acellular allogenic
      dermis or acellular porcine dermis was also compared. Histological examination
      and follow-up were made in some cases. RESULTS: After tangential excision, eschar
      excision and scar excision, the wounds were covered with either allogenic
      acellular dermis or porcine acellular dermis and autologous split-thickness skin.
      The take rate was found to be (93.4 +/- 3.4)%, (92.1 +/- 4.6)%, (94.5 +/- 3.5)%,
      respectively. There was no a significant difference in take rate (P > 0.05). No
      significant difference in take rate between the transplantation of allogenic
      acellular dermis with autologous split-thickness skin and transplantation of
      porcine acellular dermis with autologous split-thickness skin was found (P >
      0.05). When autologous split-thickness skin harvested from the trunk or
      extremities was used, the take rate was (93.1 +/- 4.8)%, (89.0 +/- 6.2)%,
      respectively, whereas the take rate was only about 70% - 80% when skin harvested
      from the scalp was used. The take rate was only about 40% when acellular
      allogenic dermis and autologous micro-skin graft were used to cover the wound.
      Histological examination 19 months after the transplantation revealed normal
      structure. Collagenous fibers were orderly arranged. There was no apparent
      hyperplasia of collagenous fibers. Hair follicles, sweat glands and other skin
      appendages were not found in the healed area. Grossly, no obvious pigmentation
      was seen, the surface was smooth with slight wound contraction, and the
      consistency was flexible. CONCLUSION: Acellular allogenic split-thickness dermis
      or acellular porcine split-thickness dermis with autologous split-thickness
      dermis for coverage of deep burn wound and the wound of scar excision is an ideal
      material.

PMID- 11832168
TI  - Relative risk factors analysis of 3,922 cases of gallbladder cancer.
AB  - OBJECTIVE: To make clear the relationship between gallstones and gallbladder
      cancer, the relationship between the size of gallstones and gallbladder cancer,
      the course of gallbladder cancer, and the relationship among adenoma and
      carcinoma of gallbladder and ascariasis in the biliary tract. METHODS: A total of
      3,922 cases of gallbladder cancer from 28 provinces in china from 1986 to 1998
      were reviewed, according to a standard protocol called "the clinical
      epidemiological list of gallbladder cancer". RESULTS: Gallbladder cancer
      accounted for 0.4% - 3.8% of bile tract disease in the same period, averaging
      1.53%. Gallbladder cancer accounted for 0.1% - 1.1% of abdominal surgery in the
      same period. Gallstones were found in 46.7% of the cases of gallbladder cancer,
      the related risk (RR) of gallbladder cancer with gallstones was 13.7. The average
      course with gallstones was 10 - 15 years. The gallstone in gallbladder was 3 cm
      or above in diameter. The ratio of the progression from adenoma to carcinoma of
      gallbladder was 1.5%. Only 4 cases of ascariasis was reported. CONCLUSIONS:
      Gallbladder cancer and gallstones are closely associated. Patients with gallstone
      of 3 cm or above in diameter and a course of 10 - 15 years are usually at an
      increased risk for cancer. We found the adenoma and carcinoma of gallbladder are
      closely related, and there is no relationship between gallbladder cancer and
      ascariasis in our group.

PMID- 11832169
TI  - [Thoracolumbar injuries: pathomorphology of and a new classification].
AB  - OBJECTIVE: To introduce a new classification of thoracolumbar injuries. METHODS:
      Three modes were used to classify the injuries according to the mechanisms of
      injuries: Type A, flexion-compression fractures; Type B, vertical compression
      fractures; Type C, distraction injuries. Two groups were used to distinguish the
      fractures in one type according to the pathomorphological differences and the
      clinical incidence: Group A, with a more clinical incidence, and Group B, with a
      less clinical incidence. Three subgroups were used to divide the injuries in one
      group in consideration of the severity of the fracture instability and the
      fracture displacement: fracture, subluxation, and dislocation. RESULTS: A new
      classification of thoracolumbar fractures was established. CONCLUSION: The new
      classification is more systemic and more convenient.

PMID- 11832170
TI  - [Diagnosis and treatment of thoracic myelopathy due to degenerative thoracic
      spine disease].
AB  - OBJECTIVE: To summarize the experience in the early diagnosis and treatment of
      chronic thoracic myelopathy due to the compression of degenerative thoracic spine
      disease. METHODS: 21 patients with thoracic spinal stenosis were operated on from
      January 1995 to April 2000. Etiologically 16 patients were found to have
      ossification of the ligamentum flovum, 3 Scheuermann's disease, and 2 DISH. They
      were confirmed by CT, CTM, MRI and Magnetic MEP. Decompression was performed by
      en block unroof laminectomy for the posterolateral wall of the thoracic canal.
      The epstein criteria were used to judge the operative results. RESULTS: In the 21
      patients 5 belonged to localized type, 10 continuous type, and 3 skip type in 21
      cases. Three patients showed a compression from the anterior side, and 3 were
      complicated by OPLL of the cervical spine. Results were excellent in 4 patients,
      good in 8, improved in 2, and poor in 1. One patient was operated on two times
      because the extent of laminectomy was not enough for the first operation.
      CONCLUSIONS: Early diagnosis can be made if orthopedists are familiar with the
      clinical characteristics of thoracic myelopathy, and are alert to thoracic spine
      stenosis. En block unroof laminectomy is effective and safe to treat thoracic
      spine stenosis.

PMID- 11832171
TI  - [Sagittal profile restoration of thoracolumbar fracture with rod rotation and in
      situ bending technique].
AB  - OBJECTIVE: To restore the sagittal profile at the time of regaining vertebral
      height during surgery of thoracolumbar fracture by rotation, screw-hook
      combination and in situ bending technique. METHODS: In 48 patients who have been
      treated since 1997, 41 were male and 7 female. Their age ranged from 17 to 54
      years. Surgical procedures were (L(1) fracture for example): CD or TSRH pedicle
      screws inserted in T(12) and L(2), offset laminar hooks placed on T(11) and L(2),
      and two rods contoured according to the normal sagittal profile of the
      instrumental segment and inserted into the pedicle screws with the rod contouring
      curve in the frontal plane. Distraction force was used to regain vertebral
      height. The rods were rotated by 90 degrees and fixed with the set screws. The
      contouring curve of the rod at this time was transferred from the frontal plane
      to the sagittal plane where the normal sagittal profile was restored. The offset
      laminar hooks were compressed toward the screws. If lordosis was not
      satisfactory, the rods could be bent in situ. Posterolateral bone grafting was
      finally performed. RESULTS: No death and no neurological worsening were noted
      except deep infection in one patient. Average vertebral height was restored by
      96%. 39 patients had complete restoration of vertebral height. Sagittal kyphotic
      Cobb angle was corrected from average 24 degrees before operation to average -2
      degrees after operation. Follow-up (20 months on average) showed no
      pseudarthrosis but two screws broken in one patient. CONCLUSIONS: Rod rotation
      and in situ rod bending technique can satisfactorily restore the normal sagittal
      profile and regain vertebral height. Offset laminar hooks can effectively protect
      pedicle screws, and minimise mechanical failure of instrumentation.

PMID- 11832172
TI  - [Unsuccessful operative treatment of acute thoracic and thoracolumbar injuries
      with neurologic deficit].
AB  - OBJECTIVE: To analyze the main factors for unsuccessful operative treatment of
      acute thoracic and thoracolumbar injuries with neurologic deficit. METHODS: 82
      patients with acute thoracic and thoracolumbar injuries with neurologic deficit
      who had had unsuccessful operations in other hospitals were reviewed. Clinical
      materials and radiographs including plane and functional films and CT scans were
      analyzed. RESULTS: In the 82 patients 30 had unsuccessful reduction or spinal
      deformity, and 31 canal encroachment. In 12 pedicle screws located out of the
      pedicle, 2 penetrated the canal and 3 pressed against the aorta. 41 patients who
      complained back pain, 16 had mechanical spinal instability, and 3 neurological
      instability. CONCLUSION: The main factors for unsuccessful operative management
      include inappropriate selection of surgical indications and inaccurate use of
      surgical technique.

PMID- 11832173
TI  - [Influence of solid thoracolumbar kyphosis on lumbar spine and surgical
      treatment].
AB  - OBJECTIVE: To investigate the influence of solid thoracolumbar kyphosis on the
      lumbar spine and surgical treatment. METHODS: 14 had solid kyphosis of the
      thoracolumbar spine. Cobb angle of kyphosis of the thoracolumbar spine and
      lordosis between L(2)/S(1), L(2)/L(5), L(2)/L(3), L(3)/L(4), L(4)/L(5), L(5)/S(1)
      pre- and post-osteotomy was measured respectively, and the amount of vertebrae
      slipped over 3mm was recorded. The results were compared with those of the normal
      group respectively. RESULTS: The Cobb angles of lordosis between L(2)/S(1),
      L(2)/L(5), L(2)/L(3), L(3)/L(4), L(4)/L(5), L(5)/S(1) in the deformity group were
      increased significantly compared with those that of the normal group
      respectively; obvious changes in percentage occurred in the segment between
      L(2)/L(3) and L(3)/L(4). Over lordosis of the lumbar spine was greatly corrected
      postosteotomy of the thoracolumbar spine, it was still significantly different
      compared with that of the normal group. In 9 patients with retrolisthesis of 20
      vertebrae, 70% occurred in L(2) and L(3) vertebrae. The amount of retrolisthesis
      of vertebrae decreased to 3 in two patients. No retrolisthesis of vertebra was
      seen in the normal group. Single-stage procedures combined with anterior
      releasing and posterior osteotomy through facet joints for kyphosis of the
      thoracolumbar spine showed a correction. rate of 85.7%, but single-stage
      osteotomy through the posterior vertebra showed a correction rate of 60.7%. Seven
      of 8 patients who had had seriously back pain complained of no pain or slight
      backache after operation. 40% of the patients showed functional improvement in
      the sphincter of the urinary bladder and anus. 50% of the patients had
      improvement in muscle strength. CONCLUSIONS: Kyphosis of the thoracolumbar spine
      may result in over lordosis of the lumbar spine and retrolisthesis of vertebrae,
      which are obvious in the upper lumbar spine. These changes may lead to back pain.
      Correction of kyphosis of the thoracolumbar spine may obviously decrease over
      lordosis of the lumbar spine and inclination of vertebral slip, and may further
      decrease the overload to the posterior column of the spine and relieve back pain.
      Osteotomy combined with anterior and posterior procedures is effective and safe
      in the correction of kyphosis of the thoracolumbar spine.

PMID- 11832174
TI  - [Cervical spine operation using coralline hydroxyapatite].
AB  - OBJECTIVE: To study the result of using coralline hydroxyapatite (CHA) in
      cervical anterior fusion and posterior laminoplasty operation. METHODS: 45
      patients of cervical operation using CHA were followed up. Of these patients, 27
      received anterior fusion and titanium plate fixation (34 levels fused). 18 with
      spinal stenosis at least at 3 levels, (posterior spinal process-splitting
      laminoplasty) had 79 split spinal processes fused by CHA. The average follow-up
      time was 25.9 months. RESULTS: The union rate of CHA was 85.3% in average by
      anterior approach. The height and angle of the fused level and the anterior
      salient were well maintained. The JOA score improvement rate was 58.7%. The CHA
      grafts were kept well between the split spinous processes with a union rate of
      70.9%. After operation, the spinal cord moved dorsally, and the flat rate was
      improved from 0.19 to 0.41. No apparent posterior salient occurred. The JOA score
      improvement rate was 51%. CONCLUSION: The effect of CHA in cervical antero
      posterior operation is similar to that of autograft bone, and it is unnecessary
      to resect a piece of bone from a health region of the body.

PMID- 11832175
TI  - [Posterior atlantoaxial facet screw fixation in rheumatoid arthritis].
AB  - OBJECTIVE: To clarify the characteristics of the clinicopathological factors in
      cases of atlantoaxial instability due to rheumatoid and to introduce a new method
      for the treatment of this disease. METHODS: Fifteen patients with atlantoaxial
      instability due to rheumatoid were treated with posterior facet screws to obtain
      immediate rigid fixation of C(1 - 2). In this series of patients, screw fixation
      was augmented with an interspinous C(1 - 2) strut graft which was wired in place
      to provide three-point stabilization and to facilitate bone fusion. RESULTS: In
      each patient fixation was satisfactory, and C(1 - 2) alignment and stability were
      restored without complication due to instrumentation. All patients showed osseous
      union (a mean follow-up period of 10 months; range 6 - 14 months). CONCLUSION:
      Posterior atlantoaxial facet screw fixation provides immediate three-dimension
      rigid fixation of C(1 - 2) that is biomechanically superior to wiring or other
      fixation.

PMID- 11832176
TI  - [The relationship between effects and radiation doses of intra-arterial
      phosphorus-32 glass microspheres embolization therapy for patients with advanced
      liver cancer].
AB  - OBJECTIVE: To evaluate the relationship between effects and internal radiation of
      phosphorus-32 glass microspheres embolization therapy for liver cancer patients.
      METHODS: From 1994 to 1998, 44 patients with unresectable liver cancer received
      intra-arterial radio-embolization therapy using (32)P-GMS. Preoperative and
      postoperative function and energy level of the liver were tested by liver
      function test and arterial blood ketone body ratio (AKBR). CT, single photon
      emission computer tomography (SPECT), and AFP were used to judge the effect of
      the therapy; multivariate analysis was made. RESULTS: In the moderate dose group,
      low incidence of complication, high tumor shrinking rate and AFP decreasing rate,
      and long-term survival rate were observed. In the larger dose group, high
      incidence of liver failure, high tumor shrinking rate and AFP decreasing rate,
      and long-term survival rate were also observed. In the low dose group, low
      incidence of complication, but low tumor shrinking rate and AFP decreasing rate
      and long-term survival rate were not observed. CONCLUSIONS: The reasonable
      radiation doses for liver cancer patients may be about 30 Gy; if liver cirrhosis
      is serious, the doses can be reduced.

PMID- 11832177
TI  - [Measurement of tumor angiogenesis in primary lung cancer].
AB  - OBJECTIVE: To study tumor angiogenesis in primary lung cancer and its relation
      with lymph node metastasis, tumor cell apoptosis, and cell proliferation.
      METHODS: Intratumor microvessel was detected by factor VIII polyclonal antibody
      using immunohistochemistry. Tumor cell apoptosis was detected by TUNEL method.
      Cell proliferation was analyzed by flow cytometry. RESULTS: Intratumor
      microvessel density (MD) was significantly lower in stage I lung cancer than in
      stage II and stage III (P < 0.01). MD was significantly higher in the tumors with
      lymph node metastasis (P < 0.01). With the increase in MD, there would be a 1.2
      fold increase in the risk of lymph node metastasis (P < 0.01). With the increase
      of MD, apoptosis index (AI) of the tumor significantly decreased, but no
      relationship between MD and cell proliferation index (PI) was observed.
      CONCLUSION: Tumor angiogenesis promotes growth and metastasis of lung cancer.
      Tumor angiogenesis also can inhibit the apoptosis of lung cancer.

PMID- 11832178
TI  - [An occlusive evaluation proposal to intra-saccular embolization of intracranial
      aneurysm].
AB  - OBJECTIVE: To explore the imaging criteria for evaluating intracranial aneurysm
      embolization. METHODS: Angiographic occlusive criteria for intracranial aneurysm
      embolization (aneurysm not opcified angiographically after embolization, 100%
      occlusion; a little part of aneurysm neck residual, 95%; neck residual, 90%; neck
      and a little part of aneurysm cavity residual, 80%; some cavity residual, < 80%)
      were used by 6 specialists to evaluate 121 aneurysms embolized with MDS
      (mechanical detachable spiral) and/or GDC (guglielmi detachable coil) from March
      1995 to July 1999. The rationality, feasibility and limitation of the criteria
      were discussed. RESULTS: Among the 121 aneurysms, 100% occlusion was reached in
      53 aneurysms (43.8%), 95% in 27 (22.3%), 90% in 16 (13.2%), 80% in 15 (12.4%),
      and less than 80% in 10 (8.3%) respectively. Good accordance was obtained among
      different doctors in the occlusive evaluation of aneurysm embolization.
      CONCLUSIONS: The suggesting criteria are simple and feasible in clinical
      practice, although the effect of imaging follow-up of embolized aneurysm is
      unknown and the numerical value of occlusive percentage is arbitrary.

PMID- 11832179
TI  - [Application of extracardiac conduit total cavopulmonary anastomosis].
AB  - OBJECTIVE: To evaluate the value of application of extracardiac conduit total
      cavopulmonary anastomosis (TCPA) in complex heart disease. METHODS: From June
      1998 to August 1999, 10 patients with functional univentricular complex
      congenital heart diseases received TCPA. Eight patients were male and 2 female
      with a mean age of (9.0 +/- 5.6) years (from 2.5 to 21 years) and a mean weight
      of (25 +/- 14) kg (from 11 to 45 kg). Associated heart anomalies were TGA, PS or
      ASD. All surgical procedures were performed under general anesthesia and
      hypothermia. RESULTS: No operative and postoperative deaths and all patients were
      followed up for 6 - 18 months. All patients were clinically asymptomatic. There
      was no increase of systemic venous pressure. EKG revealed no arrhythmias. The
      cardiac function was in NYHA class I-II. CONCLUSIONS: Extracardiac conduit TCPA
      is a simple procedure and it is superior to others.

PMID- 11832180
TI  - [Endoscopy-assisted neurosurgery for intracranial operation].
AB  - OBJECTIVE: To investigate the value of endoscope-assisted neurosurgery for
      intracranial operation. METHODS: 37 patients with intracranial lesions including
      tumors, aneurysms, cysts, hematomas, hydrocephalus and nerve-vessel compression
      syndrome were treated with this method. Their results were compared to those of
      microsurgery and macrosurgery. The items analyzed included exposure and
      protection of brain tissue and cranial nerves, views of operation field, length
      of procedure etc. RESULTS: 15 patients with tumors, showed a high rate of
      complete removal but less complications. The 6th nerves of CPA tumors operation
      were preserved. Six cases of nerve-vessel compression syndrome showed excellent
      therapeutic effects. In 8 cases of intraventricle lesions, using endoscope easily
      found tumor location and the cause of hydrocephalus. As to saccular diseases,
      endoscope was used to deal with the major location. In 4 cases of hematomas, less
      blot remained and the procedure shortened. Moreover the operation field was more
      clear and adequate on the expenses of no more complexity of the procedure.
      CONCLUSIONS: Endoscope-assisted microsurgery is helpful in intracranial
      operation. It might become a standard neuro-operation in near future.

PMID- 11832181
TI  - [Diagnosis and treatment of pheochromocytoma].
AB  - OBJECTIVE: To improve the diagnosis and treatment of pheochromocytoma. METHODS:
      From 1958 to 1998, 286 cases of pheochromocytoma, confirmed by open surgery and
      pathology, were retrospectively analyzed. RESULTS: The tumors in the adrenal
      gland were seen in 220 cases, and in the external adrenal gland in 66. Of 29
      cases of malignant pheochromocytomas, 7 were noted in the adrenal and 22 in the
      external adrenal gland. 19 cases showed stationary pheochromocytomas without
      clinical features. Total resections were performed in 281 cases. CONCLUSION: The
      operative mortality could be reduced by the prevention of potential
      myocardiopathy. The diagnosis of malignant pheochromocytoma should depend upon
      the long-term follow up.

PMID- 11832182
TI  - [Portal anticoagulation in preventing thrombosis after porta-azygous
      devascularization for portal hypertension].
AB  - OBJECTIVE: To study the prevention method for thrombosis after porta-azygous
      devascularization for portal hypertension. METHODS: 71 patients with portal
      hypertension due to cirrhosis were divided into group A (36 patients) and group B
      (35 patients). In group A, a anticoagulation tube was inserted via splenic vein
      branch during shunt and anticoagulation therapy was given after operation.
      RESULTS: All the patients received color Doppler examination 3 months after
      operation. No thrombosis occurred in the group A and thrombosis occurred in 13
      patients (37.14%) in the group B. CONCLUSION: Portal anticoagulation therapy is
      the effective in preventing portal thrombosis after porta-azygous
      devascularization for portal hypertension.

PMID- 11832183
TI  - [Resection of pelvic retroperitoneal neoplasm and reconstruction of iliac blood
      vessels: report of 22 cases].
AB  - OBJECTIVE: To study the surgical manipulation of iliac blood vessels invaded by
      pelvic tumors in order to raise the resection rate. METHODS: We reviewed 22 cases
      of resection for pelvic retroperitoneal tumors along with the reconstruction of
      iliac blood vessels in our hospital from July 1994 to January 2000. In 22 cases,
      8 received operation on the right iliac arteries and veins, and 14 on the left.
      RESULTS: Follow-up for 4 months to 5 years and 10 months (average 3.6 years)
      showed that 3 patients had recurrence and needed secondary operation. All the
      grafts were patent except one vein graft occlusion 7 months after operation.
      CONCLUSION: Resection of pelvic retroperitoneal neoplasm combined with
      reconstruction of iliac blood vessels is safe, effective and practical to raise
      the excision rate and decrease the recurrence rate.

PMID- 11832184
TI  - [Time course of TGF beta 1 and VEGF expression in experimental vein grafts].
AB  - OBJECTIVE: To investigate time course of TGF beta(1) and VEGF expression and
      their role in intimal hyperplasia. METHODS: In situ hybridization and
      immunohistochemical technique were used to detect the time course of intimal
      hyperplasia, time course of TGF beta(1) mRNA and protein expression of TGF
      beta(1) and VEGF. RESULTS: After autogenous vein replacement, the obvious
      neointima was seen at 2 weeks, and peaked at 8 weeks. The expression of TGF
      beta(1) mRNA peaked at 1 week and decreased gradually, but at 10 weeks, its
      positive cell percentage was still 10.1%. Both protein expression of TGF beta(1)
      and VEGF in VSMCs increased from 24 hours after grafting and peaked at 2 weeks.
      Their positive cell percentages were 40.6% and 36.6% respectively. After 4 weeks,
      their expression decreased at 8 weeks, the positive cell percentages were 8.9%
      and 13.8% respectively. CONCLUSIONS: TGF beta(1) plays an important part in ECM
      accumulation by promoting ECM synthesis and decreasing ECM degradation. VEGF
      plays the key role in reendothelialization. They may affect each other and
      cooperated in the formation of intimal hyperplasia.

PMID- 11832185
TI  - [Changes in bladder compliance and detrusor contraction/relaxation of diabetic
      rats].
AB  - OBJECTIVE: To provide experimental basis for further study on the mechanism of
      diabetic cystopathy (DCP). METHODS: The bladder compliance and
      contraction/relaxation of whole bladder/detrusor strips were evaluated in vitro
      on diabetic rats. RESULTS: Significant decrease of detrusor
      contraction/relaxation and increase of bladder compliance were observed (P <
      0.01). The contractile force of diabetes, diuresis and control were (20.80 +/-
      6.38), (31.66 +/- 6.17) and (40.10 +/- 7.21) g/100 mg T respectively.
      CONCLUSIONS: The results suggest that both the injury of detrusor
      contraction/relaxation and bladder compliance are important factors for diabetic
      cystopathy, however, diuresis does not play a major role in the development of
      DCP.

PMID- 11832186
TI  - [The modulating effect of panax pseudoginseng wall saponins on the DAG-PKC signal
      pathway and TNF secretion of macrophages].
AB  - OBJECTIVE: To explore the roles of panax pseudoginseng wall saponins on the DAG
      PKC signal pathway and TNF secretion of macrophages. METHODS: The changes of the
      activities of postburn inositol lipid signal system factors such as PLC, DAG,
      cytomembrane PKC, cytoplasma PKC, and intracellular calcium concentration and the
      secretory amount of macrophage TNF were observed. RESULTS: Panax pseudoginseng
      wall saponins could reduce the increased PLC activity from 57.58 +/- 8.19 to
      27.00 +/- 2.31 and the intracellular calcium concentration from 393.18 +/- 392.62
      to 90.56 +/- 7.21. With the role of panax pseudoginseng wall saponins, DAG
      activity reduced from 488.10 +/- 40.20 to 288.30 +/- 30.00, cytomembrane PKC
      activity decreased from 3081.50 +/- 698.50 to 1699.50 +/- 218.50, and cytoplasmic
      PKC activity from 2 188.60 +/- 258.30 to 848.40 +/- 138.30. The secretory TNF
      amount of macrophage decreased by 55%. CONCLUSION: Panax pseudoginseng wall
      saponins might play an very important role in the modulating of the DAG-PKC
      signal pathway and decreased TNF secretion of macrophage.

PMID- 11832187
TI  - Relations of tumor suppressor gene p16 and RB to early diagnosis of lung cancer.
AB  - OBJECTIVES: To study the incidence and mechanism of the tumor suppressor gene p16
      and RB inactivation in lung cancer, and to investigate their relations to
      biological characteristics, clinical pathological diagnosis and gene
      classification. METHODS: Immunohistochemistry, double in situ hybridization, PCR,
      PCR-SSCP, and sequencing were used to study the changes in the p16 and RB genes
      in 106 patients with lung cancer. The specimen of normal lung tissue from the
      patients with lung cancer and specimens of the 23 patients with benign lung
      diseases were studied in contrast to those of the same patients. RESULTS: The
      total expression rate of the p16 and RB genes in the lung cancer tissues of the
      106 patients was lower than that in normal lung tissues and tissues of benign
      lung diseases and was specially related to histological type, metastasis, and
      clinical stage of lung cancer. In stage I and II lung cancer, the obvious
      inactivation rate of the tumor suppressor gene p16 or RB was 32.6% or 28.3%. The
      p16 inactivation appeared largely in non-small cell lung cancer (50.1%), and the
      RB inactivation largely in small cell lung cancer (88.2%). Homozygous deletion,
      methylation, and mutation were three mechanisms for the p16 gene inactivation.
      The deletion rate of the p16 exon 1 and/or exon 2 was 25.8% in the patients with
      non-small cell lung cancer. Fifteen patients (16.9%) showed methylation at the
      SmaI sites of CpG island of the p16 gene. PCR-SSCP and sequencing revealed p16
      gene mutation in 9 of the 106 patients with lung cancer. CONCLUSIONS: The p16 and
      RB genes may play an important role in genesis and progression of lung cancer.
      The inactivation of the p16 or RB gene may be an early sign of lung canceration,
      that is important for the early diagnosis. A new gene classification model for
      lung cancer diagnosis would be set up based on the research of the p16 and RB
      genes.

PMID- 11832188
TI  - [Diagnosis and treatment of primary retroperitoneal teratoma].
AB  - OBJECTIVE: To study the diagnosis and treatment of primary retroperitoneal
      teratoma in adults. METHODS: The clinical data of 36 adult patients with primary
      retroperitoneal teratoma were reviewed. RESULTS: Nine patients were male and 27
      female. Twenty-four patients (66.7%) aged (30.4 +/- 8.0) years were benign, and
      12 patients (36.3%) aged (39.6 +/- 10.5) years were malignant. Four (21.1%) cases
      of presacral tumors and 8 (47.1%) of 17 cases of epigastric tumors were
      malignant. Clinical features included abdominal or presacral masses and
      compression symptoms with or without tumor markers. All patients, except one with
      liver metastasis, underwent radical resection. Patients without malignant
      metastasis survived, but 5 patients with malignant metastasis survived more than
      2 years after operation. CONCLUSIONS: Malignant metastasis of retroperitoneal
      teratoma is closely related to the age of adults. Early radical resection is the
      optimal treatment. Adjuvant chemotherapy can induce a short-time remission in
      those with germ cell elements.

PMID- 11832189
TI  - [CT guided percutaneous fine needle aspiration for early diagnosis of pancreatic
      infection after acute necrotizing pancreatitis].
AB  - OBJECTIVE: To assess CT-guided percutaneous fine needle aspiration (FNA) for
      early diagnosis of pancreatic infection after acute necrotizing pancreatitis.
      METHODS: CT-guided percutaneous FNA was employed to diagnose pancreatic infection
      after acute necrotizing pancreatitis in 14 patients. The aspirates were smeared,
      cultured and subjected polymerase to chain reaction (PCR) for detecting bacteria.
      RESULTS: Ten patients were diagnosed as having pancreatic infection and 4 non
      pancreatic infection. FNA was totally performed for 15 times: left
      retroperitoneal route for 12 times, left and right retroperitoneal route for one
      time, and transperitoneal route for two times. The sensitivity of smear, PCR,
      culture to diagnose pancreatic infection was 7/10, 9/10, 10/10, respectively.
      Their specificity was 4/4, and the time for obtaining the results was 30 minutes,
      4 hours, 3 days respectively. CONCLUSIONS: Retroperitoneal approach can be used
      for most patients with acute necrotizing pancreatitis when performing CT guided
      percutaneous FNA. PCR of aspirates is a rapid and accurate method to diagnose
      pancreatic infection.

PMID- 11832190
TI  - [Surgical treatment of recurrent dislocation of the patella in children].
AB  - OBJECTIVE: To study an operative method for repair of recurrent dislocation of
      the patella in children. METHODS: 36 children with recurrent patellar dislocation
      were treated surgically at an average age of 9.1 years. They were followed on
      average for 4 years and 4 months. Nine of the 36 children underwent bilateral
      repair, with 45 knees were treated. The combined soft tissue operations included
      lateral retinacular releasing, medial retinacular tightening of the knee, vastus
      medialis muscle transfer to the patella, medial and distal transfer of the half
      patellar tendon. RESULTS: 28 patients had stable knee joint and a full range of
      motion, and improved sports activity after operation. Seven children achieved
      satisfactory function of the knee joint but there was no significant difference
      between pre-and postoperative sports exercise ability. One child suffered from a
      redislocation of the patella. Wound infection was not seen and the range of knee
      joint motion was not restricted in all patients. CONCLUSIONS: The combined
      procedures for repair of recurrent dislocation of the patella in children risk
      free for growth disturbances secondary to iatrogenic injury to the proximal
      tibial physis. It is safe and effective for recurrent dislocation of the patella
      in skeletally immature children.

PMID- 11832191
TI  - [Anterior interbody autografting and internal fixation for primary surgical
      management of thoracolumbar spinal tuberculosis].
AB  - OBJECTIVES: To verify the importance of early reconstruction of spinal stability
      and to evaluate the safety of anterior instrumentation in surgical management of
      spinal tuberculosis. METHODS: Eleven cases of thoracolumbar spinal tuberculosis
      were treated with primary anterior debridement, interbody autografting and Z
      plate fixation from October 1997 to January 1999. RESULTS: All the 11 cases
      healed without any recurrence after follow-up for an average of 16 months. Spinal
      fusion occurred in 3.8 months on average after surgery. 18 degrees of kyphosis
      correction was achieved with no associated complication. CONCLUSIONS: Early
      reconstruction of spinal stability plays an important role in surgical management
      of spinal tuberculosis, and it is safe to implant anterior titanium spinal
      instrument in tuberculosis foci.

PMID- 11832192
TI  - [Telangiectatic osteosarcoma: report of 10 cases].
AB  - OBJECTIVE: To raise the level of early diagnosis of telangiectatic osteosarcoma
      (TOS). METHODS: Ten patients with TOS were treated from July 1991 to December
      1998. The patients included men 6 and 4 women, aged from 4 to 44 years (average
      23.7 years). The lesions were located at the proximal femur (1 patient), distal
      femur metaphysis (2), femur shaft (1), proximal tibia metaphysis (2), distal
      tibia (1) and humerus shaft (3). Preoperative pathologic examination showed two
      cases of TOS by open biopsy(negative by needle biopsy); the rest were found
      negative (2 patients), metastasis (1), and sarcoma (5) by needle biopsy. Eight
      patients received preoperative chemotherapy. Operations including limb-salvage
      (3) and amputation (7) were performed in all patients. All patients accepted
      postoperative chemotherapy. RESULTS: 10 Follow-up for a mean of 28 months (range
      6 - 72 months) showed no local recurrences: disease-free in 4 patients and
      pulmonary metastasis in, 6, of whom 5 died and 1 is still alive with lung
      metastasis. CONCLUSION: TOS is often misdiagnosed and needs early diagnosis and
      correct treatment under the cooperation of clinicians, radiologists and
      pathologists.

PMID- 11832193
TI  - [Modified sternal turnover with pedicle of abdominal rectus muscle for pectus
      excavatum].
AB  - OBJECTIVE: To assess surgical correction for children with pectus excavatum.
      METHOD: Modified sternal turnover operation with rectus abdominalis pedicle was
      performed on 20 children with pectus excavatum since 1987. RESULTS: The patients
      were successfully corrected and no recurrence was seen during 6 to 36 months
      after operation. Human bone density examination showed same results in some
      patients before and six months after operation. CONCLUSION: Modified sternal
      turnover operation has the following advantages: easy to operate; less bleeding;
      better blood supply to the turned sternum; rapid postoperative recovery;
      satisfied correction of deformity and no recurrence. It should be widely used
      clinically.

PMID- 11832194
TI  - [Reversal of severe left ventricular dilatation after operation and its
      correlation with cardiac function].
AB  - OBJECTIVE: To investigate the relationship between the reversal of left
      ventricular dilatation and postoperative cardiac function, and prognosis.
      METHODS: 16 patients with severely dilated left ventricle underwent
      echocardiographic examinations preoperatively and at discharge (7 - 10 days after
      operation). Left ventricular (LV) diameters were measured (LVEDD, LVESD) and
      matched to body surface area (LVEDDI, LVESDI) and fractional shortening (FS);
      left ventricular ejection fraction (EF) was calculated. RESULTS: Left ventricular
      dimensions significantly decreased at discharge after operation. Preoperative
      LVEDD was (78.54 +/- 6.30) mm and postoperative LVEDD (63.77 +/- 13.69) mm (P <
      0.01). Preoperative LVESD (60.03 +/- 8.95) mm and postoperative LVESD (53.23 +/-
      12.68) mm (P < 0.05). Preoperative LVEDDI was (44.10 +/- 5.24) mm/m(2) and
      postoperative LVEDDI (36.01 +/- 9.53) mm/m(2) (P < 0.01). Preoperative LVESDI was
      (34.78 +/- 6.22) mm/m(2) and postoperative LVESDI (30.90 +/- 9.19) mm/m(2) (P <
      0.05). Left atrium (LA) dimension was shorter after operation than before
      operation. Left ventricular construction didn't improve postoperatively, even
      temporarily decreased at discharge. Preoperative EF was (48.00 +/- 11.71)% and
      postoperative EF (40.15 +/- 8.69)% (P < 0.01). Preoperative FS was (22.82 +/-
      6.27)% and postoperative FS (19.63 +/- 3.42) (P > 0.05). The incidence of
      postoperative cardiac arrhythmia was 75%. No dimension changes were observed in 2
      patients with severely dilated left ventricles after operation: one (LVEDDI 56
      mm/m(2)) died, and the other had severe low cardiac output. Six of 14 who had
      reduced dilated left ventricle didn't reach normal limits, still in the range of
      severe dilated left ventricule (LVEDDI > 37 mm/m(2)). CONCLUSIONS: Most patients
      decreased the dimension of left ventricular size early after operation, but some
      had partial recovery from severe ventricular dilatation. Although left
      ventricular dimensions (LVEDD, LVESD, LVEDDI, LVESDI) significantly reduced,
      cardiac function didn't improve at once with the reversal of left ventricular
      dilatation, but temporarily decreased after operation and the incidence of
      cardiac arrhythmia was high.

PMID- 11832195
TI  - [Re-surgical treatment for postoperative local recurrence of lung cancer].
AB  - OBJECTIVE: To evaluate the feasibility of re-surgical treatment for postoperative
      recurrence of lung cancer and its indications. METHOD: The clinical data of 20
      patients treated again surgically after recurrence of lung cancer were analyzed
      retrospectively. RESULTS: The resectability, radical resectability, morbidity,
      and mortality were 75.0% (15/20), 80.0% (12/15), 20.0% and 0.0% respectively. The
      mean operative blood loss was 945 ml. The percentages of patients with pleural
      adhesion and intrapericardial dissection were 100.0% and 53.3% separately. The 1
      year, 3-year and 5-year survival rates were 94.1%, 41.7% and 40.0%. The mean
      survival time of the patients receiving exploration or palliative resection was
      15.0 months, shorter than the 56.9 months of the patients having radical
      resection. The mean survival time of the patients with N(0) was (105.3 +/- 82.0)
      months, much longer than (11.4 +/- 6.0) months of the patients with N(1) or N(2).
      CONCLUSION: Because of extensive adhesion, operations for postoperative
      recurrence of lung cancer are difficult, but if recurrence is found in time and
      operative indication is appropriate, re-surgical treatment can prolong the
      patients' survival time.

PMID- 11832197
TI  - [Staple in pericardial devascularization of upper GI bleeding due to portal
      hypertension: application and therapeutic effect].
AB  - OBJECTIVE: To investigate the therapeutic effect of staple in pericardial
      devascularization on upper GI bleeding due to portal hypertension. METHODS: From
      July, 1997 to July, 2000, 30 portal hypertensive patients were treated by using
      pericardial devascularization plus partial resection of lower part of the
      esophagus with staple (CDH25). The eliminating rate of varicose veins of the
      lower part of the esophagus and the stenosis rate of anastomosis were evaluated.
      The therapeutic effect of pericardial devascularization without lower part
      esophageal resection in 28 patient with upper GI bleeding due to portal
      hypertension was taken as control. RESULTS: All the patients were followed up for
      23 months. There was no death due to the operation. All patients in the study
      group had no upper GI rebleeding during the 23-month follow-up. The rebleeding
      rate in the control group was 18% (5/28) (P < 0.05 vs. Study group). The varicose
      veins eliminating rate was 100% in the study group and 53.6% (15/28) in the
      control group (P < 0.01); the stenosis rate of anastomosis was 6.7% (2/30) in the
      study group. CONCLUSION: The therapeutic effect of pericardial devascularization
      could be improved by the use of staple with shorter operative time.

PMID- 11832196
TI  - [Expression of tumor metastasis gene MTA 1 in hepatocellular carcinoma: clinical
      implications].
AB  - OBJECTIVE: To evaluate the relevance of the expression of tumor metastasis gene
      metastasis-associated 1 (MTA 1) to HCC metastasis. METHODS: A fragment of MTA 1
      cDNA was synthesized by reverse transcription (RT)-PCR. A DIG-labeled method of
      in situ hybridisation (ISH) was used to measure semiquantitatively MTA 1 mRNA in
      formalin-fixed, paraffin-embedded sections. RESULTS: Most of MTA 1 mRNA positive
      cells were located on the border of the tumor in some invasive HCC. High MTA 1
      expression was found to correlate significantly with portal venous invasion,
      intrahepatic metastasis, tumor size or distant metastasis (P < 0.05), but not
      with gender, cirrhosis or AFP level. It also significantly predicted a shorter
      survival (P < 0.05). CONCLUSION: The overexpression of MTA 1 correlates closely
      with the invasion process of HCC.

PMID- 11832198
TI  - [Graf's ultrasound examination method in assessment of dysplasia and congenital
      dislocation of infant hip].
AB  - OBJECTIVE: To discuss the application of Graf's sonographic method in assessment
      of developmental dysplasia and dislocation of infant hip. METHODS: 2258 infants
      (4516 hips) were examined and evaluated by Graf's method. RESULTS: The analysis
      of data showed that type I hip accounted too 78.99%, type II 20.56%, and type III
      and type IV 0.45%. CONCLUSION: Graf's method can provide qualitative and
      quantitative evaluation for hips of infants in 3 months after birth. It is an
      effective in developmental dysplasia of the hip (DDH) and is also useful for
      early treatment and follow-up of DDH.

PMID- 11832199
TI  - [Hyperplasia of chromaffin cells in adrenocortical hyperplasia and adenoma].
AB  - OBJECTIVE: To study whether there is chromaffin cells hyperplasia in
      adrenocortical hyperplasia and adenoma. METHODS: Chromaffin cells with
      chromogranin A were marked by immunohistochemistry method. RESULTS: In 52 cases
      of adrenocortical hyperplasia and adenoma 3 were associated with eochromocyte
      hyperplasia and 5 with micro-pheochromocytoma. Six of the 8 cases were
      characterized by hypercortiso (or aldostero)-hypercatecholamine clinically.
      CONCLUSIONS: Few cases of adrenocortical hyperplasia and adenoma may be
      associated with pheochromocytic hyperplasia and micro-pheochromocytoma, and may
      be characterized by symptoms of hypercortiso (or aldostero)-hypercatecholamine.

PMID- 11832200
TI  - [Protective effect of nitric oxide on pancreas and its relation to sulfhydryl
      compounds and oxygen free radicals].
AB  - OBJECTIVE: To investigate the effect of endogenous nitric oxide (NO) on acute
      necrosis pancreatitis in rats and its relation to sulfhydryl compounds and lipid
      peroxidation. METHODS: Acute necrosis pancreatitis in rats was induced by
      retrograde sodium taurocholate (5%) infusion into the pancreatobiliary duct (1
      ml/kg body weight), and N(G)-nitro-L-arginine (L-NNA) was used as the inhibitor
      of endogenous NO. The effect of endogenous NO on pancreatic injury, serum amylase
      level, the pancreatic tissue levels of sulfhydryl compounds, and malonaldehyde
      (MDA, the end product of lipid peroxidation) was evaluated, respectively.
      RESULTS: Sodium taurocholate administration induced evident pancreatic tissue
      edema and acinar necrosis, and intrapancreatic hemorrhage occurred in 2/7 rats.
      Both serum amylase and tissue MDA [(1.25 +/- 0.28) nmol/mg x pr vs. (0.5 +/-
      0.03) nmol/mg x pr, P < 0.05] were significantly increased, but tissue sulfhydryl
      compounds were decreased markedly. Pretreatment with the NO inhibitor, L-NNA
      (12.5 mg/kg body weight), significantly intensified acinar necrosis and increased
      the intrapancreatic hemorrhage (10/12). L-NNA also resulted in a further increase
      of serum amylase and tissue MDA [(3.0 +/- 0.40) vs. (1.25 +/- 0.28) nmol/mg x pr,
      P < 0.05], but it had no effect on the tissue sulfhydryl compounds. CONCLUSION:
      Endogenous NO has the effect of pancreatic protection, and its antioxidation may
      be responsible, at least in part, for the protective mechanisms. Sulfhydryl
      compounds may not be involved in NO's pancreatic protection mechanisms.

PMID- 11832201
TI  - [Hyperpolarized cardiac arrest with ATP-sensitive potassium channel opener on
      myocardial protection during CPB].
AB  - OBJECTIVE: To investigate the myocardial protective effects of pinacidil-induced
      hyperpolarized arrest and compare them with those induced with depolarized
      hyperkalemic arrest. METHODS: 18 dogs were equally divided into three groups. In
      the hypothermic hyperpolarization group (LH group), after aortic cross-clamping,
      a single dose of 4 degrees C pinacidil containing St. Thomas cardioplegic was
      infused through the aortic root. Temperature during CPB was kept between 26 - 28
      degrees C and warmed to 37 degrees C before aortic declamping. Global ischemia
      lasted 60 min and then reperfusion started for 30 min. In the normothermic
      hyperpolarized group (WH group), the same procedure was set as in the LH group,
      except maintaining temperature of 35 - 37 degrees C for CPB and pinacidil
      solution. In the control group (group C), no pinacidil in St. Thomas solution was
      the only difference to the other 2 groups. Cardiac arrest and its recovery, the
      ultrastructure of the myocardium and hemodynamic during ischemia and after
      reperfusion were observed in the 3 groups. RESULTS: (1) The percentages of normal
      mitochondria and glycogen were not changed significantly during ischemia and
      after reperfusion in the LH group, but declined markedly in the group C at
      ischemic 30, 60 min, and reperfusion for 20 min (P < 0.01). In the WH group, they
      were lower than those of the group LH, but higher than those of the group C
      before ischemia. (2) The recoveries of CO, SV, CI, LVSW, RVSW, MAP in the LH
      group were significantly better than those in the other two groups after
      reperfusion for 15 minutes and 30 minutes (P < 0.05 or 0.01). However, they were
      much better in the WH group than in the group C (P < 0.05 or 0.01). (3) The time
      from cardioplegic infusion to cardiac arrest was shorter in the group C and the
      group LH than in the group WH. CONCLUSIONS: Myocardial protection for global
      ischemia during CPB could be well achieved with hyperpolarized cardiac arrest
      induced by ATP-sensitive potassium channel opener, pinacidil, especially in the
      hypothermic state. The protection is weaker in normothermia but is still stronger
      than that with traditional depolarized arrest.

PMID- 11832202
TI  - [Cloning and identifying of renal cell carcinoma differentially expressed genes].
AB  - OBJECTIVE: To clone and identify RCC specially expressed genes different with
      normal kidney tissue. METHODS: A technique called suppression subtractive
      hybridization was used to construct the library which contains the differently
      expressing cDNAs between RCC and normal kidney. Then the RCC specially expressed
      genes were cloned from it. RESULTS: Human RCC subtractive library with high
      subtractive efficiency was set up successfully. The amplified library contains
      350 positive clones. Sequence analysis was performed in 5 clones. All of the
      sequences were unknown before and the cDNA inserting GYLZ-RCC18 had three copies.
      Northern blot analysis showed that GYLZ-RCC18 cDNA expressed highly in RCC, but
      there was no any signal could be detected in normal kidney. Using SMART RACE
      technique, we obtained the full length of novel gene of GYLZ-RCC18. We also
      identified that GYLZ-RCC18 family contains 3 subtype genes. CONCLUSIONS: The
      highly efficient cDNA subtractive library lays a solid foundation for screening
      and cloning new and specific oncogenes or tumor suppressor genes of RCC. The
      novel differentially expressed genes provide an important clue to studying the
      mechanism of the occurrence and development of RCC.

PMID- 11832203
TI  - [Effects of p16 and GM-CSF combined gene therapy on immune response of tumor
      bearing mice].
AB  - OBJECTIVE: To investigate the effects of p16 and GM-CSF combined gene therapy on
      immune response of tumor-bearing mice (Renca). METHODS: The model of renal tumor
      bearing mice was constructed by subcutaneous injection of Renca cells. The tumor
      bearing mice were divided into 5 groups at random three days after injection of
      Renca cells. Different groups of mice were given different treatments. The
      antitumor immune responses and the survival time of mice were tested.
      Histopathologic analysis of tumor tissue was done. RESULTS: Enhancement of
      antitumor immune responses and prolongation of survival period were observed more
      obviously in tumor-bearing mice after combined therapy than in those of the other
      four groups. CONCLUSIONS: p16 and GM-CSF combined gene therapy can enhance the
      antitumor immune responses of mice and inhibit the growth of pre-established
      renal cell carcinoma.

PMID- 11832204
TI  - Cancer modeling in the modern era: progress and challenges.
AB  - Genetically engineered mouse models have contributed extensively to the field of
      cancer research. The ability to manipulate the mouse germline affords numerous
      approaches toward understanding the complexities of this disease, possibly
      providing accurate preclinical models for therapeutic and diagnostic advances.
      This review highlights some of the current strategies for modeling cancer in the
      mouse, recent accomplishments, and key remaining challenges.

PMID- 11832205
TI  - Cancer as a complex genetic trait: tumor susceptibility in humans and mouse
      models.
AB  - Cancer directly affects at least one-third of the human population, but the
      inherited genetic determinants of cancer risk remain largely unknown. Mouse
      models of human cancer are helping us to understand this disease as a complex
      genetic trait and thus to identify the multiple genetic variant alleles involved
      in pathways that affect individual cancer susceptibility.

PMID- 11832206
TI  - Apoptosis: a link between cancer genetics and chemotherapy.
AB  - Defects in apoptosis underpin both tumorigenesis and drug resistance, and because
      of these defects chemotherapy often fails. Understanding the molecular events
      that contribute to drug-induced apoptosis, and how tumors evade apoptotic death,
      provides a paradigm to explain the relationship between cancer genetics and
      treatment sensitivity and should enable a more rational approach to anticancer
      drug design and therapy.

PMID- 11832207
TI  - The role of PML in tumor suppression.
AB  - The PML gene, involved in the t(15;17) chromosomal translocation of acute
      promyelocytic leukemia (APL), encodes a protein which localizes to the PML
      nuclear body, a subnuclear macromolecular structure. PML controls apoptosis, cell
      proliferation, and senescence. Here, we review the current understanding of its
      role in tumor suppression.

PMID- 11832208
TI  - Cancer susceptibility and the functions of BRCA1 and BRCA2.
AB  - Inherited mutations in BRCA1 or BRCA2 predispose to breast, ovarian, and other
      cancers. Their ubiquitously expressed protein products are implicated in
      processes fundamental to all cells, including DNA repair and recombination,
      checkpoint control of cell cycle, and transcription. Here, I examine what is
      known about the biological functions of the BRCA proteins and ask how their
      disruption can induce susceptibility to specific types of cancer.

PMID- 11832209
TI  - The Mre11 complex is required for repair of hairpin-capped double-strand breaks
      and prevention of chromosome rearrangements.
AB  - Inverted repeats (IRs) that can form a hairpin or cruciform structure are common
      in the human genome and may be sources of instability. An IR involving the human
      Alu sequence (Alu-IR) has been studied as a model of such structures in yeast. We
      found that an Alu-IR is a mitotic recombination hotspot requiring
      MRE11/RAD50/XRS2 and SAE2. Using a newly developed approach for mapping rare
      double-strand breaks (DSBs), we established that induction of recombination
      results from breaks that are terminated by hairpins. Failure of the mre11, rad50,
      xrs2, and sae2 mutants to process the hairpins blocks recombinational repair of
      the DSBs and leads to generation of chromosome inverted duplications. Our results
      suggest an additional role for the Mre11 complex in maintaining genome stability.

PMID- 11832210
TI  - FtsK Is a DNA motor protein that activates chromosome dimer resolution by
      switching the catalytic state of the XerC and XerD recombinases.
AB  - FtsK acts at the bacterial division septum to couple chromosome segregation with
      cell division. We demonstrate that a truncated FtsK derivative, FtsK(50C), uses
      ATP hydrolysis to translocate along duplex DNA as a multimer in vitro, consistent
      with FtsK having an in vivo role in pumping DNA through the closing division
      septum. FtsK(50C) also promotes a complete Xer recombination reaction between dif
      sites by switching the state of activity of the XerCD recombinases so that XerD
      makes the first pair of strand exchanges to form Holliday junctions that are then
      resolved by XerC. The reaction between directly repeated dif sites in circular
      DNA leads to the formation of uncatenated circles and is equivalent to the
      formation of chromosome monomers from dimers.

PMID- 11832211
TI  - Separase, polo kinase, the kinetochore protein Slk19, and Spo12 function in a
      network that controls Cdc14 localization during early anaphase.
AB  - In budding yeast, the phosphatase Cdc14, a key regulator of exit from mitosis, is
      released from its inhibitor Cfi1/Net1 in the nucleolus during anaphase. A
      signaling cascade, known as the mitotic exit network (MEN), controls this
      release. We have identified a regulatory network, the FEAR (Cdc fourteen early
      anaphase release) network that promotes Cdc14 release from the nucleolus during
      early anaphase. The FEAR network is comprised of the polo kinase Cdc5, the
      separase Esp1, the kinetochore-associated protein Slk19, and Spo12. We also show
      that the FEAR network initiates Cdc14 release from Cfi1/Net1 during early
      anaphase, and MEN maintains Cdc14 in the released state during late anaphase. We
      propose that one function of Cdc14 released by the FEAR network is to stimulate
      MEN activity.

PMID- 11832212
TI  - Human interferon-gamma mRNA autoregulates its translation through a pseudoknot
      that activates the interferon-inducible protein kinase PKR.
AB  - PKR, an interferon (IFN)-inducible protein kinase activated by double-stranded
      RNA, inhibits translation by phosphorylating the initiation factor eIF2alpha
      chain. We show that human IFN-gamma mRNA uses local activation of PKR in the cell
      to control its own translation yield. IFN-gamma mRNA activates PKR through a
      pseudoknot in its 5' untranslated region. Mutations that impair pseudoknot
      stability reduce the ability to activate PKR and strongly increase the
      translation efficiency of IFN-gamma mRNA. Nonphosphorylatable mutant eIF2alpha,
      knockout of PKR and PKR inhibitors 2-aminopurine, transdominant-negative PKR, or
      vaccinia E3L correspondingly enhances translation of IFN-gamma mRNA. The
      potential to form the pseudoknot is phylogenetically conserved. We propose that
      the RNA pseudoknot acts to adjust translation of IFN-gamma mRNA to the PKR level
      expressed in the cell.

PMID- 11832213
TI  - Control of actin reorganization by Slingshot, a family of phosphatases that
      dephosphorylate ADF/cofilin.
AB  - The ADF (actin-depolymerizing factor)/cofilin family is a stimulus-responsive
      mediator of actin dynamics. In contrast to the mechanisms of inactivation of
      ADF/cofilin by kinases such as LIM-kinase 1 (LIMK1), much less is known about its
      reactivation through dephosphorylation. Here we report Slingshot (SSH), a family
      of phosphatases that have the property of F actin binding. In Drosophila, loss of
      ssh function dramatically increased levels of both F actin and phospho-cofilin (P
      cofilin) and disorganized epidermal cell morphogenesis. In mammalian cells, human
      SSH homologs (hSSHs) suppressed LIMK1-induced actin reorganization. Furthermore,
      SSH and the hSSHs dephosphorylated P cofilin in cultured cells and in cell-free
      assays. Our results strongly suggest that the SSH family plays a pivotal role in
      actin dynamics by reactivating ADF/cofilin in vivo.

PMID- 11832214
TI  - Autoinhibition of c-Abl.
AB  - Despite years of investigation, the molecular mechanism responsible for
      regulation of the c-Abl tyrosine kinase has remained elusive. We now report
      inhibition of the catalytic activity of purified c-Abl in vitro, demonstrating
      that regulation is an intrinsic property of the molecule. We show that the
      interaction of the N-terminal 80 residues with the rest of the protein mediates
      autoregulation. This N-terminal "cap" is required to achieve and maintain
      inhibition, and its loss turns c-Abl into an oncogenic protein and contributes to
      deregulation of BCR-Abl.

PMID- 11832215
TI  - Hrs regulates endosome membrane invagination and tyrosine kinase receptor
      signaling in Drosophila.
AB  - Signaling through tyrosine kinase receptors (TKRs) is thought to be modulated by
      receptor-mediated endocytosis and degradation of the receptor in the lysosome.
      However, factors that regulate endosomal sorting of TKRs are largely unknown.
      Here, we demonstrate that Hrs (Hepatocyte growth factor-regulated tyrosine kinase
      substrate) is one such factor. Electron microscopy studies of hrs mutant larvae
      reveal an impairment in endosome membrane invagination and formation of
      multivesicular bodies (MVBs). hrs mutant animals fail to degrade active epidermal
      growth factor (EGF) and Torso TKRs, leading to enhanced signaling and altered
      embryonic patterning. These data suggest that Hrs and MVB formation function to
      downregulate TKR signaling.

PMID- 11832216
TI  - Regulation of opioid receptor trafficking and morphine tolerance by receptor
      oligomerization.
AB  - The utility of morphine for the treatment of chronic pain is hindered by the
      development of tolerance to the analgesic effects of the drug. Morphine is unique
      among opiates in its ability to activate the mu opioid receptor (MOR) without
      promoting its desensitization and endocytosis. Here we demonstrate that [D-Ala(2)
      MePhe(4)-Gly(5)-ol] enkephalin (DAMGO) can facilitate the ability of morphine to
      stimulate MOR endocytosis. As a consequence, rats treated chronically with both
      drugs show reduced analgesic tolerance compared to rats treated with morphine
      alone. These results demonstrate that endocytosis of the MOR can reduce the
      development of tolerance, and hence suggest an approach for the development of
      opiate analogs with enhanced efficacy for the treatment of chronic pain.

PMID- 11832217
TI  - Structure of the reovirus membrane-penetration protein, Mu1, in a complex with is
      protector protein, Sigma3.
AB  - Cell entry by nonenveloped animal viruses requires membrane penetration without
      membrane fusion. The reovirus penetration agent is the outer-capsid protein, Mu1.
      The structure of Mu1, complexed with its "protector" protein, Sigma3, and the fit
      of this Mu1(3)Sigma3(3) heterohexameric complex into the cryoEM image of an
      intact virion, reveal molecular events essential for viral penetration. Autolytic
      cleavage divides Mu1 into myristoylated Mu1N and Mu1C. A long hydrophobic pocket
      can receive the myristoyl group. Dissociation of Mu1N, linked to a major
      conformational change of the entire Mu1 trimer, must precede myristoyl-group
      insertion into the cellular membrane. A myristoyl switch, coupling exposure of
      the fatty acid chain, autolytic cleavage of Mu1N, and long-range molecular
      rearrangement of Mu1C, thus appears to be part of the penetration mechanism.

PMID- 11832218
TI  - CaRF: a neuronal transcription factor that CaREs.
AB  - In this issue of Neuron, report the discovery of a new transcription factor,
      CaRF, that contributes to calcium stimulation of the BDNF gene through CaRE1, one
      of several calcium response elements found in the promoter of the BDNF gene. The
      CaRF/CaRE1 transcriptional pathway may control the expression of genes critical
      for activity-dependent, long-term changes in the central nervous system (CNS).

PMID- 11832219
TI  - Caudate clues to rewarding cues.
AB  - Behavioral studies indicate that prior experience can influence discrimination of
      subsequent stimuli. The mechanisms responsible for highlighting a particular
      aspect of the stimulus, such as motion or color, as most relevant and thus
      deserving further scrutiny, however, remain poorly understood. In the current
      issue of Neuron, demonstrate that neurons in the caudate nucleus of the basal
      ganglia signal which dimension of a visual cue, either color or location, is
      associated with reward in an eye movement task. These findings raise the
      possibility that this structure participates in the reward-based control of
      visual attention.

PMID- 11832220
TI  - Dissociations within association cortex.
AB  - The parietal lobes of nonhuman primates have been well characterized by single
      neuron recordings, yet clear partitioning of the human parietal lobes has not
      been clearly demonstrated. An elegant new fMRI study by Simon and colleagues
      (this issue of Neuron) suggests that parietal cortex does indeed contain
      dissociable subregions, each specialized for a particular visuomotor or cognitive
      function.

PMID- 11832221
TI  - Aph-2/Nicastrin: an essential component of gamma-secretase and regulator of Notch
      signaling and Presenilin localization.
AB  - The Notch signaling pathway plays a role in cell fate specification in many
      metazoans. A critical aspect of Notch activation involves proteolysis of the
      Notch receptor. This cleavage event requires Presenilin as a component of a large
      multiprotein complex, gamma-secretase. This complex mediates a similar cleavage
      event of the beta-amyloid precursor protein (APP). The transmembrane protein
      Nicastrin has been found to associate with Presenilin, Notch, and APP. Recent
      biochemical and genetic studies have focused on elucidating the function of this
      protein.

PMID- 11832222
TI  - Theta oscillations in the hippocampus.
AB  - Theta oscillations represent the "on-line" state of the hippocampus. The
      extracellular currents underlying theta waves are generated mainly by the
      entorhinal input, CA3 (Schaffer) collaterals, and voltage-dependent Ca(2+)
      currents in pyramidal cell dendrites. The rhythm is believed to be critical for
      temporal coding/decoding of active neuronal ensembles and the modification of
      synaptic weights. Nevertheless, numerous critical issues regarding both the
      generation of theta oscillations and their functional significance remain
      challenges for future research.

PMID- 11832223
TI  - Whole brain segmentation: automated labeling of neuroanatomical structures in the
      human brain.
AB  - We present a technique for automatically assigning a neuroanatomical label to
      each voxel in an MRI volume based on probabilistic information automatically
      estimated from a manually labeled training set. In contrast to existing
      segmentation procedures that only label a small number of tissue classes, the
      current method assigns one of 37 labels to each voxel, including left and right
      caudate, putamen, pallidum, thalamus, lateral ventricles, hippocampus, and
      amygdala. The classification technique employs a registration procedure that is
      robust to anatomical variability, including the ventricular enlargement typically
      associated with neurological diseases and aging. The technique is shown to be
      comparable in accuracy to manual labeling, and of sufficient sensitivity to
      robustly detect changes in the volume of noncortical structures that presage the
      onset of probable Alzheimer's disease.

PMID- 11832224
TI  - An instructive role for retinal waves in the development of retinogeniculate
      connectivity.
AB  - A central hypothesis of neural development is that patterned activity drives the
      refinement of initially imprecise connections. We have examined this hypothesis
      directly by altering the frequency of spontaneous waves of activity that sweep
      across the mammalian retina prior to vision. Activity levels were increased in
      vivo using agents that elevate cAMP. When one eye is made more active, its layer
      within the LGN is larger despite the other eye having normal levels of activity.
      Remarkably, when the frequency of retinal waves is increased in both eyes,
      normally sized layers form. Because relative, rather than absolute, levels of
      activity between the eyes regulate the amount of LGN territory devoted to each
      eye, we conclude that activity acts instructively to guide binocular segregation
      during development.

PMID- 11832225
TI  - Regulation of chemosensory receptor expression and sensory signaling by the KIN
      29 Ser/Thr kinase.
AB  - Sensory signals regulate multiple developmental and behavioral circuits in C.
      elegans, providing a genetically tractable system in which to investigate the
      mechanisms underlying the acquisition and integration of sensory information. kin
      29 mutants are defective in the expression of a set of chemoreceptor genes, and
      exhibit characteristics associated with altered sensory signaling, including
      increased lifespan, decreased body size, and deregulated entry into the dauer
      developmental stage. kin-29 encodes a Ser/Thr kinase with similarity to the MARK
      and AMPK/SNF1 family of kinases. We show that KIN-29 acts cell-autonomously and
      non-cell-autonomously in sensory neurons to regulate chemoreceptor expression,
      body size, and the dauer decision, suggesting that kin-29 function is essential
      for the correct acquisition and transduction of sensory information.

PMID- 11832226
TI  - A calcium-responsive transcription factor, CaRF, that regulates neuronal activity
      dependent expression of BDNF.
AB  - Transcription of the brain-derived neurotrophic factor (BDNF) gene is regulated
      in a calcium- and neuron-selective manner; however, the mechanisms that underlie
      this selectivity are not known. We have characterized a new calcium-response
      element, CaRE1, that is required for activity-dependent transcription of BDNF
      exon III and have cloned a transcription factor, CaRF, that activates
      transcription from BDNF promoter III in a CaRE1-dependent manner. The
      transcriptional activity of CaRF is regulated in a calcium- and neuron-selective
      manner, suggesting that CaRF may confer selectivity upon the activity-dependent
      induction of BDNF exon III expression.

PMID- 11832227
TI  - Three-dimensional structure of the complexin/SNARE complex.
AB  - During neurotransmitter release, the neuronal SNARE proteins synaptobrevin/VAMP,
      syntaxin, and SNAP-25 form a four-helix bundle, the SNARE complex, that pulls the
      synaptic vesicle and plasma membranes together possibly causing membrane fusion.
      Complexin binds tightly to the SNARE complex and is essential for efficient
      Ca(2+)-evoked neurotransmitter release. A combined X-ray and TROSY-based NMR
      study now reveals the atomic structure of the complexin/SNARE complex. Complexin
      binds in an antiparallel alpha-helical conformation to the groove between the
      synaptobrevin and syntaxin helices. This interaction stabilizes the interface
      between these two helices, which bears the repulsive forces between the apposed
      membranes. These results suggest that complexin stabilizes the fully assembled
      SNARE complex as a key step that enables the exquisitely high speed of Ca(2+)
      evoked neurotransmitter release.

PMID- 11832228
TI  - Differential control of vesicle priming and short-term plasticity by Munc13
      isoforms.
AB  - Presynaptic short-term plasticity is an important adaptive mechanism regulating
      synaptic transmitter release at varying action potential frequencies. However,
      the underlying molecular mechanisms are unknown. We examined genetically defined
      and functionally unique axonal subpopulations of synapses in excitatory
      hippocampal neurons that utilize either Munc13-1 or Munc13-2 as synaptic vesicle
      priming factor. In contrast to Munc13-1-dependent synapses, Munc13-2-driven
      synapses show pronounced and transient augmentation of synaptic amplitudes
      following high-frequency stimulation. This augmentation is caused by a Ca(2+)
      dependent increase in release probability and releasable vesicle pool size, and
      requires phospholipase C activity. Thus, differential expression of Munc13
      isoforms at individual synapses represents a general mechanism that controls
      short-term plasticity and contributes to the heterogeneity of synaptic
      information coding.

PMID- 11832229
TI  - Calcium dynamics of spines depend on their dendritic location.
AB  - Dendritic spines are morphologically and functionally heterogeneous. To
      understand this diversity, we use two-photon imaging of layer 5 neocortical
      pyramidal cells and measure action potential-evoked [Ca(2+)]i transients in
      spines. Spine calcium kinetics are controlled by (i) the diameter of the parent
      dendrite, (ii) the length of the spine neck, and (iii) the strength of spine
      calcium pumps. These factors produce different calcium dynamics in spines from
      basal, proximal apical, and distal apical dendrites, differences that are more
      pronounced without exogenous buffers. In proximal and distal apical dendrites,
      different calcium dynamics correlate with different susceptibility to synaptic
      depression, and modifying calcium kinetics in spines changes the expression of
      long-term depression. Thus, the spine location apparently determines its calcium
      dynamics and synaptic plasticity. Our results highlight the precision in design
      of neocortical neurons.

PMID- 11832230
TI  - The life cycle of Ca(2+) ions in dendritic spines.
AB  - Spine Ca(2+) is critical for the induction of synaptic plasticity, but the
      factors that control Ca(2+) handling in dendritic spines under physiological
      conditions are largely unknown. We studied [Ca(2+)] signaling in dendritic spines
      of CA1 pyramidal neurons and find that spines are specialized structures with low
      endogenous Ca(2+) buffer capacity that allows large and extremely rapid [Ca(2+)]
      changes. Under physiological conditions, Ca(2+) diffusion across the spine neck
      is negligible, and the spine head functions as a separate compartment on long
      time scales, allowing localized Ca(2+) buildup during trains of synaptic stimuli.
      Furthermore, the kinetics of Ca(2+) sources governs the time course of [Ca(2+)]
      signals and may explain the selective activation of long-term synaptic
      potentiation (LTP) and long-term depression (LTD) by NMDA-R-mediated synaptic
      Ca(2+).

PMID- 11832231
TI  - Evidence for a modified V3 with dorsal and ventral halves in macaque monkeys.
AB  - Through more than 30 years of research, the nature of the third visual area, V3,
      and even its existence have been in question. Here, we used injections of up to
      five distinguishable tracers into both dorsal and ventral portions of V1 of
      macaque monkeys (representing the lower and upper visual quadrant, respectively)
      to provide compelling evidence for a V3 that is smaller than V2. This V3 includes
      both dorsal and ventral halves mirroring dorsal and ventral V2 in retinotopic
      organization. Of the approximately ten areas with V1 connections, V3 appears to
      account for about 20%.

PMID- 11832232
TI  - Feature-based anticipation of cues that predict reward in monkey caudate nucleus.
AB  - A subset of caudate neurons fires before cues that instruct the monkey what he
      should do. To test the hypothesis that the anticipatory activity of such neurons
      depends on the context of stimulus-reward mapping, we examined their activity
      while the monkeys performed a memory-guided saccade task in which either the
      position or the color of a cue indicated presence or absence of reward. Some
      neurons showed anticipatory activity only when a particular position was
      associated with reward, while others fired selectively for color-reward
      associations. The functional segregation suggests that caudate neurons
      participate in feature-based anticipation of visual information that predicts
      reward. This neuronal code influences the general activity level in response to
      visual features without improving the quality of visual discrimination.

PMID- 11832233
TI  - Topographical layout of hand, eye, calculation, and language-related areas in the
      human parietal lobe.
AB  - To identify subdivisions of the human parietal cortex, we collected fMRI data
      while ten subjects performed six tasks: grasping, pointing, saccades, attention,
      calculation, and phoneme detection. Examination of task intersections revealed a
      systematic anterior-to-posterior organization of activations associated with
      grasping only, grasping and pointing, all visuomotor tasks, attention and
      saccades, and saccades only. Calculation yielded two distinct activations: one
      unique to calculation in the bilateral anterior IPS mesial to the supramarginal
      gyrus and the other shared with phoneme detection in the left IPS mesial to the
      angular gyrus. These results suggest human homologs of the monkey areas AIP, MIP,
      V6A, and LIP and imply a large cortical expansion of the inferior parietal lobule
      correlated with the development of human language and calculation abilities.

PMID- 11832234
TI  - Winging it--actin on the fly.
AB  - How actin dynamics might be regulated to generate specific cellular structures
      during development remains something of a mystery. New insights may be gained
      from the recent identification of a conserved cofilin phosphatase, Slingshot,
      which modulates actin dynamics to help control Drosophila wing hair
      morphogenesis.

PMID- 11832235
TI  - Hip1 and Hippi participate in a novel cell death-signaling pathway.
AB  - Neuronal apoptosis is a cardinal feature of late-onset neurodegenerative
      disorders such as Alzheimer's and Huntington's disease. Biochemical and cell
      biological studies point to a role for Hip1 and Hippi in caspase-8 activation and
      the initiation of apoptosis during the pathogenesis of Huntington's disease.

PMID- 11832236
TI  - Signaling survival: how axons rescue their glia.
AB  - The trophic theory of cell survival hypothesizes that cell number is regulated by
      survival signals generated by other cells. Work published in this issue of
      Developmental Cell confirms that neurons can provide trophic support for glia in
      Drosophila, and fills in important molecular details of this interaction.

PMID- 11832237
TI  - A new clue at the nuclear pore: RanBP2 is an E3 enzyme for SUMO1.
AB  - A recent paper in Cell shows that the large nucleoporin RanBP2 can act as an E3
      enzyme for the ubiquitin-like protein SUMO1. These intriguing results raise
      important questions about the mechanism of SUMO1 conjugation, the relationship of
      SUMO1 to nuclear transport, and the regulation of RanBP2 in the pore.

PMID- 11832238
TI  - Calculating the potential of C2 domains for membrane binding.
AB  - A recent report in Molecular Cell demonstrates the ability of electrostatic
      calculations to predict the membrane binding properties of structurally
      characterized C2 domains and assign probable membrane targeting functions to
      numerous uncharacterized C2 domains.

PMID- 11832239
TI  - Building beauty: the genetic control of floral patterning.
AB  - Floral organ identity is controlled by combinatorial action of homeotic genes
      expressed in different territories within the emerging flower. This review
      discusses recent progress in our understanding of floral homeotic genes, with an
      emphasis on how their region-specific expression is regulated.

PMID- 11832240
TI  - The utility of prions.
AB  - Infectious, self-propagating protein aggregates (prions) as well as structurally
      related amyloid fibrils have traditionally been associated with neurodegenerative
      diseases in mammals. However, recent work in fungi indicates that prions are not
      simply aberrations of protein folding, but are in fact widespread, conserved, and
      in certain cases, apparently beneficial. Analysis of prion behavior in yeast has
      led to insights into the mechanisms of prion appearance and propagation as well
      as the effect of prions on cellular physiology and perhaps evolution. The prion
      forming proteins of Saccharomyces cerevisiae are members of a larger class of
      Gln/Asn-rich proteins that is abundantly represented in the genomes of higher
      eukaryotes, raising the prospect of genetically programmed prion-like behavior in
      other organisms.

PMID- 11832241
TI  - Cell migration in development and disease.
AB  - A recent meeting at the Max Delbruck Center in Berlin, Germany provided a forum
      to discuss the molecular mechanisms of cell migration in a broad range of
      contexts including chemotaxis, development, immunity, and cancer.

PMID- 11832242
TI  - Regulation of cell number by MAPK-dependent control of apoptosis: a mechanism for
      trophic survival signaling.
AB  - Trophic mechanisms in which neighboring cells mutually control their survival by
      secreting extracellular factors play an important role in determining cell
      number. However, how trophic signaling suppresses cell death is still poorly
      understood. We now show that the survival of a subset of midline glia cells in
      Drosophila depends upon direct suppression of the proapoptotic protein HID via
      the EGF receptor/RAS/MAPK pathway. The TGFalpha-like ligand SPITZ is activated in
      the neurons, and glial cells compete for limited amounts of secreted SPITZ to
      survive. In midline glia that fail to activate the EGFR pathway, HID induces
      apoptosis by blocking a caspase inhibitor, Diap1. Therefore, a direct pathway
      linking a specific extracellular survival factor with a caspase-based death
      program has been established.

PMID- 11832243
TI  - Intrinsic differences between the superficial and deep layers of the Xenopus
      ectoderm control primary neuronal differentiation.
AB  - In Xenopus, primary neurons differentiate early, in the deep layer of the
      neuroectoderm. In contrast, the neural precursors of the superficial layer
      continue to proliferate. We report that superficial layer precursors differ from
      deep layer precursors in that they are refractory to the neuronal-promoting
      activity of bHLH genes, dominant-negative X-Delta-1, FGF-8, or signals from the
      organizer. In this system, neuronal differentiation is guided by an early
      established, intrinsic, cell-autonomous difference in the competence of the
      precursor cells to differentiate. This difference may be controlled in part by
      ESR6e, a bHLH gene of the Enhancer-of-split family, which is expressed in the
      superficial layer of the late blastula and when expressed ectopically suppresses
      primary neurogenesis in the deep layer.

PMID- 11832244
TI  - Two isoforms of the Drosophila RNA binding protein, how, act in opposing
      directions to regulate tendon cell differentiation.
AB  - Differential RNA metabolism regulates a wide array of developmental processes.
      Here, we describe a mechanism that controls the transition from premature
      Drosophila tendon precursors into mature muscle-bound tendon cells. This
      mechanism is based on the opposing activities of two isoforms of the RNA binding
      protein How. While the isoform How(L) is a negative regulator of Stripe, the key
      modulator of tendon cell differentiation, How(S) isoform elevates Stripe levels,
      thereby releasing the differentiation arrest induced by How(L). The opposing
      activities of the How isoforms are manifested by differential rates of mRNA
      degradation of the target stripe mRNA. This mechanism is conserved, as the
      mammalian RNA binding Quaking proteins may similarly affect the levels of Krox20,
      a regulator of Schwann cell maturation.

PMID- 11832245
TI  - The anaphase-promoting complex and separin are required for embryonic anterior
      posterior axis formation.
AB  - Polarization of the one-cell C. elegans embryo establishes the animal's anterior
      posterior (a-p) axis. We have identified reduction-of-function anaphase-promoting
      complex (APC) mutations that eliminate a-p polarity. We also demonstrate that the
      APC activator cdc20 is required for polarity. The APC excludes PAR-3 from the
      posterior cortex, allowing PAR-2 to accumulate there. The APC is also required
      for tight cortical association and posterior movement of the paternal pronucleus
      and its associated centrosome. Depletion of the protease separin, a downstream
      target of the APC, causes similar pronuclear and a-p polarity defects. We propose
      that the APC/separin pathway promotes close association of the centrosome with
      the cortex, which in turn excludes PAR-3 from the posterior pole early in a-p
      axis formation.

PMID- 11832246
TI  - Signal sequences control gating of the protein translocation channel in a
      substrate-specific manner.
AB  - N-terminal signal sequences mediate targeting of nascent chains to the
      endoplasmic reticulum and facilitate opening of the protein translocation channel
      to the passage of substrate. We have assessed each of these steps for a diverse
      set of mammalian signals. While minimal differences were seen in their targeting
      function, signal sequences displayed a remarkable degree of variation in
      initiating nascent chain access to the lumenal environment. Such substrate
      specific properties of signals were evolutionarily conserved, functionally
      matched to their respective mature domains, and important for the proper
      biogenesis of some proteins. Thus, the sequence variations of signals do not
      simply represent functional degeneracy, but instead encode critical differences
      in translocon gating that are coordinated with their respective passengers to
      facilitate efficient translocation.

PMID- 11832247
TI  - Direct interaction between Rab3b and the polymeric immunoglobulin receptor
      controls ligand-stimulated transcytosis in epithelial cells.
AB  - We have examined the role of rab3b in epithelial cells. In MDCK cells, rab3b
      localizes to vesicular structures containing the polymeric immunoglobulin
      receptor (pIgR) and located subjacent to the apical surface. We found that GTP
      bound rab3b directly interacts with the cytoplasmic domain of pIgR. Binding of
      dIgA to pIgR causes a dissociation of the interaction with rab3b, a process that
      requires dIgA-mediated signaling, Arg657 in the cytoplasmic domain of pIgR, and
      possibly GTP hydrolysis by rab3b. Binding of dIgA to pIgR at the basolateral
      surface stimulates subsequent transcytosis to the apical surface. Overexpression
      of GTP-locked rab3b inhibits dIgA-stimulated transcytosis. Together, our data
      demonstrate that a rab protein can bind directly to a specific cargo protein and
      thereby control its trafficking.

PMID- 11832248
TI  - The SREBP pathway in Drosophila: regulation by palmitate, not sterols.
AB  - In mammals, synthesis of cholesterol and unsaturated fatty acids is controlled by
      SREBPs, a family of membrane-bound transcription factors. Here, we show that the
      Drosophila genome encodes all components of the SREBP pathway, including a single
      SREBP (dSREBP), SREBP cleavage-activating protein (dSCAP), and the two proteases
      that process SREBP at sites 1 and 2 to release the nuclear fragment. In cultured
      Drosophila S2 cells, dSREBP is processed at sites 1 and 2, and the liberated
      fragment increases mRNAs encoding enzymes of fatty acid biosynthesis, but not
      sterol or isoprenoid biosynthesis. Processing requires dSCAP, but is not
      inhibited by sterols as in mammals. Instead, dSREBP processing is blocked by
      palmitic acid. These findings suggest that the ancestral SREBP pathway functions
      to maintain membrane integrity rather than to control cholesterol homeostasis.

PMID- 11832249
TI  - Drosophila's insulin/PI3-kinase pathway coordinates cellular metabolism with
      nutritional conditions.
AB  - Studies in Drosophila have characterized insulin receptor/phosphoinositide 3
      kinase (Inr/PI3K) signaling as a potent regulator of cell growth, but its
      function during development has remained uncertain. Here we show that inhibiting
      Inr/PI3K signaling phenocopies the cellular and organismal effects of starvation,
      whereas activating this pathway bypasses the nutritional requirement for cell
      growth, causing starvation sensitivity at the organismal level. Consistent with
      these findings, studies using a pleckstrin homology domain-green fluorescent
      protein (PH-GFP) fusion as an indicator for PI3K activity show that PI3K is
      regulated by the availability of dietary protein in vivo. Hence we surmise that
      an essential function of insulin/PI3K signaling in Drosophila is to coordinate
      cellular metabolism with nutritional conditions.

PMID- 11832250
TI  - Cholesterol and mood states at 3 days after delivery.
AB  - The aim of this study was to investigate the relationship between cholesterol and
      mood states in the initial puerperal period. The Profile of Mood States (POMS)
      was administered to 72 women on the third day after normal pregnancy,
      uncomplicated vaginal delivery and healthy baby. Plasma cholesterol concentration
      was measured the same day. Our study indicates that reduced plasma cholesterol
      concentration is associated with major feelings of fatigue and depressed mood.
      The implications of these results are discussed.

PMID- 11832252
TI  - The validity of the Hospital Anxiety and Depression Scale. An updated literature
      review.
AB  - OBJECTIVE: To review the literature of the validity of the Hospital Anxiety and
      Depression Scale (HADS). METHOD: A review of the 747 identified papers that used
      HADS was performed to address the following questions: (I) How are the factor
      structure, discriminant validity and the internal consistency of HADS? (II) How
      does HADS perform as a case finder for anxiety disorders and depression? (III)
      How does HADS agree with other self-rating instruments used to rate anxiety and
      depression? RESULTS: Most factor analyses demonstrated a two-factor solution in
      good accordance with the HADS subscales for Anxiety (HADS-A) and Depression (HADS
      D), respectively. The correlations between the two subscales varied from.40 to.74
      (mean.56). Cronbach's alpha for HADS-A varied from.68 to.93 (mean.83) and for
      HADS-D from.67 to.90 (mean.82). In most studies an optimal balance between
      sensitivity and specificity was achieved when caseness was defined by a score of
      8 or above on both HADS-A and HADS-D. The sensitivity and specificity for both
      HADS-A and HADS-D of approximately 0.80 were very similar to the sensitivity and
      specificity achieved by the General Health Questionnaire (GHQ). Correlations
      between HADS and other commonly used questionnaires were in the range.49 to.83.
      CONCLUSIONS: HADS was found to perform well in assessing the symptom severity and
      caseness of anxiety disorders and depression in both somatic, psychiatric and
      primary care patients and in the general population.

PMID- 11832251
TI  - A cross-sectional study of the prevalence of psychopathology in adults with
      congenital heart disease.
AB  - OBJECTIVE: Several studies have suggested high levels of psychopathology in
      children and adolescents with congenital heart disease (CHD). However, little
      information is published relating to psychopathology in adults with CHD. We
      wanted to estimate the prevalence of psychopathology in adults with CHD. DESIGN:
      A cross-sectional study of attenders at an adult CHD clinic compared with
      orthopaedic outpatients of the same hospital. SETTING: A tertiary CHD clinic in
      South Wales, the comparison group being recruited from the orthopaedic outpatient
      clinic in the same teaching hospital. PARTICIPANTS: One hundred and one
      individuals attending the CHD clinic were identified, 87 successfully completed
      questionnaires. Forty-five from 80 randomly selected orthopaedic outpatients
      completed questionnaires. MAIN OUTCOME MEASURES: The General Health Questionnaire
      30 (GHQ30) and the Hospital Anxiety and Depression Scale (HADS). RESULTS: We
      found a statistically significant difference in the mean GHQ 30 score between the
      CHD and comparison groups, the CHD group having lower scores. The difference
      remained after adjustment for age and sex. The mean HADS scores differed in the
      same direction, and were of borderline statistical significance. CONCLUSIONS: In
      this study, adult subjects with CHD had a lower prevalence of psychopathology.
      Possible explanations for this finding are discussed.

PMID- 11832253
TI  - Short Form 36 and Hospital Anxiety and Depression Scale. A comparison based on
      patients with testicular cancer.
AB  - BACKGROUND: The aim of this study was to compare the scorings of anxiety and
      depression assessed by the Hospital Anxiety and Depression Scale (HADS-A
      [Anxiety] and HADS-D [Depression]) with the scorings on the eight subscales of
      Short Form 36 (SF-36) and the Physical (PCS) and Mental Component Summary (MCS)
      assessed by the same patients. METHOD: In a cross-sectional study 736 long-term
      survivors after treatment for testicular cancer (TC) completed HADS and SF-36.
      Pearson's correlation coefficients were calculated on item and scale level to
      assess the associations between the HADS and the SF-36 scales and, in particular,
      between HADS and PCS and MCS, respectively. Independent predictors for PCS and
      MCS were identified by linear regression analysis. RESULTS: HADS-A and HADS-D
      were significantly associated with the SF-36 summary scales. HADS-A explained 5%
      of the variance of PCS and 49% of the variance of MCS. The comparable figures for
      HADS-D were 10% and 45%, respectively. In the multivariate analysis the HADS-D
      scoring independently predicted the level of PCS together with the patients'
      educational level, long-lasting working disability and age (variance: 30%). Both
      HADS-D and HADS-A remained independent parameters for MCS (variance: 58%)
      together with the patient's civil status. HADS-D item D4 ("slowed down") was
      similarly associated with both PCS and MCS. CONCLUSION: In univariate analyses
      HADS-D and HADS-A were statistically associated with PCS and MCS. The highest r
      values were observed for the associations between HADS and MCS, in particular
      between HADS-A and MCS. In the multivariate analyses HADS-D, but not HADS-A,
      contributed to PCS, whereas both HADS-A and HADS-D were associated with MCS. This
      pattern of different predictions of the summary scales of SF-36 supports a
      clinical practice that anxiety and depression should be assessed separately.
      Additional use of a self-rating instrument for depression and anxiety, such as
      HADS, is recommended when SF-36 is used for quality of life (QL) assessment.

PMID- 11832254
TI  - Guideline-based early rehabilitation after myocardial infarction. A pragmatic
      randomised controlled trial.
AB  - OBJECTIVES: To determine the effectiveness of individualised educational
      behavioural treatment delivered by cardiac nurses in hospital compared to usual
      care for patients following acute myocardial infarction. METHODS: One hundred and
      fourteen consecutive patients were randomised to receive the intervention or
      usual care. Outcome assessment was by self-report questionnaire (the Hospital
      Anxiety and Depression Scale and Dartmouth COOP Health Status), interview at 1
      month, and self-report at 3 and 12 months. The primary outcome was improvement in
      the Dartmouth COOP total score from baseline to 3 months. RESULTS: Four patients
      needed to be treated to give an additional patient with improvement in health
      status at 3 months (number needed to treat [NNT] 4, 95% confidence intervals
      [CIs] 3 to 12). The intervention group were more confident about returning to
      activities 1 month after discharge from hospital. Treated patients had fewer
      further treatment needs. CONCLUSIONS: An individualised educational behavioural
      treatment delivered by cardiac nurses in hospital may have substantial benefits.
      A large-scale pragmatic RCT is needed.

PMID- 11832255
TI  - Modest contribution of psychosocial variables to hypoglycaemic awareness in Type
      1 diabetes.
AB  - OBJECTIVE: To assess relationships between hypoglycaemic awareness and diabetes
      related, psychosocial and demographic characteristics. METHOD: Ninety-eight type
      1 diabetic patients completed questionnaires on somatic awareness (Somatic
      Awareness Questionnaire, SAQ), negative affectivity (Positive And Negative
      Affectivity Schedule, PANAS), symptom beliefs, bustle and variety of daily life.
      They then performed up to 70 measurements on a hand-held computer, during 4 to 6
      weeks, at home. During every measurement, they rated the presence of 20 symptoms
      on a 0-6 scale, and estimated and measured their blood glucose level. The
      percentage of recognised hypoglycaemic episodes was calculated from these data,
      and used as a measure of hypoglycaemic awareness. RESULTS: Hypoglycaemic
      awareness was negatively associated with disease duration and antecedent
      hypoglycaemia, and positively associated with the use of an insulin pump instead
      of injections, variety in the daily life, somatic awareness, sensitivity of the
      symptom beliefs and female gender. However, only 17% of the variance in
      hypoglycaemic awareness was explained. CONCLUSIONS: Psychosocial variables
      contribute to hypoglycaemic awareness, to a moderate but statistically
      significant extent.

PMID- 11832256
TI  - The effect of parental expressed emotion on glycaemic control in children with
      Type 1 diabetes. Parental expressed emotion and glycaemic control in children.
AB  - OBJECTIVE: To measure expressed emotion (EE) in parents of young children with
      diabetes and to examine the relation between EE and glycaemic control in children
      with Type 1 diabetes in a longitudinal study over 24 months. We hypothesised that
      good glycaemic control, as measured by low glycated haemoglobin levels, would be
      predicted by high parental emotional over-involvement, low frequency of critical
      comments and absence of hostility. We predicted that these effects would be
      stronger in maternal than paternal scores. METHODS: Forty-seven children
      attending a Paediatric Diabetes Clinic and their parents were studied over 24
      months. Glycated haemoglobin was measured on three occasions, at the start of the
      study period, 12 and 24 months later. At 12 months, parental EE was measured
      using an adapted version of the Camberwell Family Interview, and child emotional
      and behavioural problems were measured using the parent version of the Child
      Behavior Checklist. Multiple regression models were used to test the hypotheses.
      RESULTS: Forty-three maternal and 33 paternal interviews of adequate quality for
      analysis were obtained. Paternal hostility was found to be associated with
      elevated glycated haemoglobin measured 12 months before interview and 12 months
      after interview, accounting for 22% and 29% of the variation in glycated
      haemoglobin respectively. CONCLUSIONS: We did not find that parental emotional
      over-involvement or criticism predicted glycaemic control. Presence of hostility
      was important, but in contrast to our hypothesis, this was paternal rather than
      maternal hostility. We suggest that (i) relatively absent, rejecting fathers play
      little role in diabetes management and children perceive this negatively, or (ii)
      mothers who are unsupported by fathers cannot in turn support their children in
      diabetes care.

PMID- 11832257
TI  - High-resolution MRI and micro-FE for the evaluation of changes in bone mechanical
      properties during longitudinal clinical trials: application to calcaneal bone in
      postmenopausal women after one year of idoxifene treatment.
AB  - OBJECTIVE: To investigate whether recently developed in vivo high-resolution
      magnetic resonance-imaging and micro-finite element techniques can monitor
      changes in bone mechanical properties during long-term clinical trials aiming at
      evaluating the efficacy of new drugs for the treatment of osteoporosis. DESIGN:
      Comparison of baseline and follow-up mechanical parameters calculated using micro
      finite element analysis of the calcaneus for subjects participating in a study
      investigating the effect of idoxifene. BACKGROUND: Contemporary measurements for
      the evaluation of bone mechanical properties, based on dual-energy X-ray
      absorptiometry measurements, are not very accurate and require large trial
      populations. METHODS: A total of 56 postmenopausal subjects received either a
      placebo, 5 mg or 10 mg per day of idoxifene. Magnetic resonance-images of the
      calcaneus were made at baseline and after one year. Mechanical parameters of a
      trabecular volume of interest in the calcaneus were calculated using micro-finite
      element analysis. RESULTS: Although there were no significant differences between
      the mean changes in the treated groups and the placebo group, there were
      significant changes from baseline within groups after one year of treatment.
      Significant changes, however, were found only for mechanical parameters and only
      in the treated groups. CONCLUSIONS: The present study is the first demonstration
      that longitudinal changes in bone mechanical properties due to trabecular micro
      architectural changes may be quantified in long-term clinical studies. Since
      significant changes in mechanical parameters were obtained for the treated groups
      whereas no significant change in bone mass was found we conclude that the
      application of these techniques may increase the clinical significance of these
      trials. RELEVANCE: A precise diagnosis of in vivo bone mechanical properties that
      accounts for (changes in) trabecular bone architecture is of particular
      importance for longitudinal clinical trials aiming at evaluating the efficacy of
      new drugs since it can lead to clinically relevant results from shorter follow-up
      intervals and may enable a reduction of the number of patients involved in the
      trial.

PMID- 11832258
TI  - A biomechanical comparison of lifting techniques between subjects with and
      without chronic low back pain during freestyle lifting and lowering tasks.
AB  - OBJECTIVE: To evaluate if chronic low back pain patients perform manual material
      handling tasks differently from control subjects. DESIGN: Comparative study using
      a repeated measures design. BACKGROUND: No study evaluated the lifting technique
      of back pain patients relative to control subjects during free style lifting and
      lowering tasks. Previous findings suggest that lowering would be more hazardous
      than lifting to the low back. It would be interesting to evaluate if chronic low
      back pain patients behave differently than controls when lifting and lowering.
      METHODS: Thirty-three male subjects (18 controls, 15 suffering from non-specific
      chronic low back pain) participated. A 12-kg box was lifted (freestyle) from the
      floor to the hips (1) in front (symmetric task) or (2) to a shelf located at 90
      degree on the right (asymmetric task) and was lowered back to the floor. A 3D
      biomechanical analysis involving the assessment of L5/S1 loading, posture of
      segments, inertial parameters, and EMG was performed. RESULTS: There was no
      difference between the groups for postural (trunk and lower limb angles),
      inertial (trunk velocity and acceleration), and L5/S1 loading (moments and
      compression) variables. The patients showed abnormally low left lumbar erector
      spinae (symmetric task, lowering) or high left thoracic erector spinae (all
      tasks) EMG activation. Significant Group x Action (lifting vs. lowering)
      interactions were also observed for some inertial and L5/S1 loading variables
      suggesting that the biomechanical differences detected between lifting and
      lowering may have a differential influence on the technique used by back pain
      patients and control subjects. CONCLUSIONS: The gross lifting technique of back
      pain patients was unaltered relative to controls but the activation of paraspinal
      muscles differed, suggesting that a more detailed biomechanical analysis, such as
      the use of EMG driven models, might be required to reveal lumbar impairments
      during lifting. RELEVANCE: To evaluate if chronic low back pain patients use
      naturally different lifting techniques to prevent pain exacerbation and damaged
      lumbar tissue overloading.

PMID- 11832259
TI  - Relative contribution of trunk muscles to the stability of the lumbar spine
      during isometric exertions.
AB  - OBJECTIVE: To compare the relative contribution of various trunk muscles to the
      stability of the lumbar spine. DESIGN: Quantification of spine stability with a
      biomechanical model. BACKGROUND: Modern low back rehabilitation techniques focus
      on muscles that stabilize the lumbar spine. However, the relative contribution of
      various trunk muscles to spine stability is currently unknown. METHODS: Eight
      male subjects performed isometric exertions in trunk flexion, extension, lateral
      bending, and axial rotation, and isometric exertions under vertical trunk loading
      and in a lifting hold. Each isometric trial was repeated three times at 20%, 40%,
      and 60% of the maximum trunk flexion force or with a load of 0%, 20%, 40%, and
      60% of body weight for the latter two exertions. Surface EMG data from 12 major
      trunk muscles were used in the biomechanical model to estimate stability of the
      lumbar spine. A simulation of each trial was performed repeatedly with one of the
      10 major trunk muscle groups removed from the model. RESULTS: Relative
      contribution of each muscle to spine stability was significantly affected by the
      combination of loading magnitude and direction (3-way interaction). None of the
      removed muscles reduced spine stability by more than 30%. CONCLUSIONS: A single
      muscle cannot be identified as the most important for the stability of the lumbar
      spine. Rather, spine stability depends on the relative activation of all trunk
      muscles and other loading variables. RELEVANCE: This study will improve our
      understanding of individual trunk muscles' contribution to overall stability of
      the lumbar spine.

PMID- 11832260
TI  - Effect of center of pressure and trunk center of mass optimization methods on the
      analysis of whole body lifting mechanics.
AB  - OBJECTIVE: This study evaluates methods to optimize the trunk center of mass
      position, the center of pressure position, or both to minimize the difference
      between horizontal location of the whole body center of mass estimated by the
      model and center of pressure measured during static postures. DESIGN: Within
      subjects repeated measures. BACKGROUND: Methods to optimize the trunk center of
      mass position have been proposed in the past, but have not been fully evaluated
      nor have accounted for errors in the location of the center of pressure.
      Accurately determining these locations affects the understanding of the control
      of balance. METHODS: Six methods were compared using kinematic and force plate
      data from 22 subjects. Static postures resembling both leg and back lifting
      techniques were used to optimize the center of mass. A typical lifting movement
      was used to evaluate the effectiveness of the methods in reducing the difference
      between external moment and time derivative of the angular momentum. RESULTS:
      Optimization of the center of pressure had a statistically significant effect on
      reducing errors (P<0.05), whereas optimization of the trunk center of mass alone
      had not (P>0.05). CONCLUSIONS: Optimizing the center of pressure was simple and
      compensated for systematic errors introduced from the model and instrumentation.
      The addition of the center of mass optimization improved some results but added
      much complexity to the experimental procedures. RELEVANCE: Reducing errors in
      determining the relative position of the center of pressure and center of mass
      enhances the understanding of balance control as this relationship reflects the
      dynamic stability of the system.

PMID- 11832261
TI  - Transverse plane kinetics during treadmill walking with and without a load.
AB  - OBJECTIVE: The purpose of this experiment was to determine the effects of wearing
      a backpack on transverse plane upper and lower body torque. BACKGROUND: During
      unloaded walking the upper and lower body counter-rotate to reduce the net
      angular momentum of the body. There is less counter-rotation while carrying a
      load, suggesting a more rigid link between the upper and lower body. We predicted
      that load carriage would result in an increase in upper body torque. Because the
      upper and lower body may be more rigidly linked during load carriage, we also
      predicted an increase in lower body torque. METHODS: Twelve subjects (5 male, 7
      female, mean age=26) walked with and without a backpack containing 40% of their
      body mass on a treadmill at speeds from 0.6 to 1.6 ms(-1). Kinematic data were
      sampled for 30 s at each speed, upper and lower body torque were calculated from
      angular acceleration and moment of inertia. RESULTS: Higher levels of upper and
      lower body torque were observed during load carriage than during unloaded
      walking. However, the increase in upper body torque was 225%, while upper body
      moment of inertia increased by 400%. CONCLUSIONS: The differences in torque
      between loaded and unloaded walking suggest that a goal of loaded walking is to
      minimize upper body torque, which may reduce the likelihood of injury. RELEVANCE:
      Knowledge of the effects of load carriage on upper and lower body torque, and
      related changes in coordination may provide insight into injury reduction
      mechanisms during load carriage.

PMID- 11832262
TI  - Lower extremity general muscle moment patterns in healthy individuals during
      recumbent cycling.
AB  - OBJECTIVE: The purpose of this study was to compare lower extremity generalized
      muscle moments across two workloads during recumbent bicycling in younger and
      older healthy adults. DESIGN: The study design was a comparative investigation of
      cycling patterns. BACKGROUND: Biomechanical data regarding muscle activation,
      kinematic, and kinetic patterns have been presented for upright cycling, but only
      a few studies have evaluated biomechanical patterns during the alternative
      configuration of recumbent cycling. METHODS: Twenty-four healthy adults,
      classified by age into two different groups, under 35 and over 50 years of age,
      rode a recumbent bicycle at a constant cadence (60-65 rpm) and at two different
      resistances (0.5 and 1.0 kg m) while kinematic and kinetic data were recorded.
      General muscle moments were calculated using joint kinematic and kinetic data via
      inverse dynamic equations. RESULTS: The ankle general muscle moment remained
      plantar flexor throughout the pedaling cycle; the knee general muscle moment
      remained flexor throughout the cycle, except during the power phase of the higher
      workload where an extensor general muscle moment was observed; and the hip
      general muscle moment was extensor with a transient flexor general muscle moment
      period during the recovery phase. Increased workload led to increases in ankle
      plantar flexor and knee extensor general muscle moment magnitudes, but no changes
      at the hip. Age had no effect on general muscle moment magnitudes or patterns.
      CONCLUSIONS: Configurational differences between the upright and recumbent
      bicycle do not affect patterns, but the total output requirements do affect the
      magnitudes of the general muscle moments. RELEVANCE: Based on previous studies,
      the recumbent bicycle appears to be a safe rehabilitation tool for post
      cerebrovascular accident and cardiorespiratory patients, but in order to more
      properly and efficiently use the recumbent bicycle as a rehabilitation tool,
      normative biomechanical data are necessary. The current study is the first such
      investigation to report normative data of lower extremity general muscle moment
      patterns during recumbent cycling. Effects of age and workload were also
      demonstrated.

PMID- 11832263
TI  - Hip joint contact forces in normal subjects and subjects with total hip
      prostheses: walking and stair and ramp negotiation.
AB  - OBJECTIVE: To calculate the hip joint contact force in normal subjects and
      subjects with total hip replacements. DESIGN: An observational study of age
      matched normal subjects and subjects with hip joint replacements. BACKGROUND: Hip
      joint contact forces have been calculated using musculo-skeletal models and
      measured in vivo using instrumented hip prostheses. There are few examples of
      studies performed on subjects in the 40-60 year age range. This study
      characterises the forces in both normal subjects and subjects with hip joint
      replacements for these 'young' subjects. METHODS: Motion analysis and force plate
      data were used as input to a three-dimensional model of the leg. Five male and
      six female normal subjects and five male subjects with hip prostheses were
      studied. Each subject was observed walking and negotiating stairs and a ramp.
      RESULTS: Hip joint contact forces in both thigh and pelvic-based co-ordinate
      systems are presented. Subjects cadence, speed and stride length are given.
      CONCLUSIONS: In general subjects with hip replacements exhibited lower hip joint
      contact forces than age matched normal subjects. It is suggested that this was
      the results of the lower speeds, stride lengths and cadences adopted by the
      subjects with hip replacements. RELEVANCE: The characterisation of hip joint
      contact forces provides essential information for prosthetic joint design and
      testing. The comparison of hip joint contact forces in normal subjects with those
      in subjects with prosthetic joints provides evidence of, not only actual use of
      joints, but also of possible levels of force that might be applied to hip
      prostheses if subjects returned to normal use.

PMID- 11832264
TI  - The effect of malalignment on stresses in polyethylene component of total knee
      prostheses--a finite element analysis.
AB  - OBJECTIVE: To investigate the effects of malalignment on stresses in tibial
      polyethylene component of total knee prostheses. DESIGN: A three-dimensional
      finite element analysis was used to calculate the contact stress and von Mises
      stress in the tibial polyethylene component subjected to a compressive load, and
      the malalignment situations were simulated. BACKGROUND: Many biomechanical
      studies to investigate the stresses in tibial polyethylene component were assumed
      at the ideal contact alignment. The effect of malalignment on stresses in tibial
      polyethylene component was not investigated extensively. METHODS: Three
      dimensional finite element models of the tibiofemoral joint of knee prostheses
      for three different designs were constructed. Three malalignment conditions
      including the medial translation (0.25, 0.5 and 1.0 mm), internal rotation (1
      degree, 3 degree and 5 degree), and varus tilt (1 degree, 3 degree and 5 degree)
      of the femoral component relative to the tibial component were simulated. A
      compression load of 3000 N was applied to the tibiofemoral joint at 0 degree of
      flexion. The maximum contact stress and von Mises stress in the tibial component
      were compared to investigate the effects of malalignment. RESULTS: In comparing
      with the neutral position, the greatest increase of maximum contact stress were
      67.6%, 14.3% and 145.9% and the greatest increase of maximum von Mises stress
      were 92.5%, 22.7% and 120.6% in maltranslation, internal rotation and varus tilt
      simulations, respectively. CONCLUSION: The greatest increase of contact stress
      and von Mises stress was occurred in the high conformity flat-on-flat design of
      knee prosthesis under the severest malalignment condition. The high conformity
      curve-on-curve design of knee prosthesis has the minimal risk of polyethylene
      wear under the malalignment conditions. RELEVANCE: This study revealed the
      importance of malalignment effect on stresses in tibial polyethylene component.
      Polyethylene wear in surface replacement total knees will be minimal when a high
      conformity curve-on-curve knee design is used and the rotational line between the
      femoral and tibial components has the least effect on polyethylene wear but
      varus/valgus malalignment, even with the best designed prosthesis will still
      accelerate wear.

PMID- 11832265
TI  - Pelvifemoral rhythm during unilateral hip flexion in standing.
AB  - OBJECTIVE: To quantify pelvifemoral rhythm during unilateral hip flexion in
      standing subjects, under different degrees of resistance. DESIGN: Descriptive and
      correlational. BACKGROUND: Pelvic rotation contributes to the change in hip
      flexion angle while individuals are supine. Degree of contribution in standing
      has not been described. METHODS: Pelvic and femoral motions, relative to
      vertical, were documented while 14 subjects performed three trials of standing
      unilateral hip flexion, both with and without a 4.53 kg ankle weight. Pelvic and
      thigh segments were marked with reflective spheres, and motion was captured by
      video analysis. RESULTS: Pelvic rotation contributed 18.1% of the change in hip
      flexion angle. Pelvic rotation occurred throughout the movement. Neither presence
      of external resistance nor direction of movement significantly changed this
      contribution. CONCLUSIONS: A strong relationship exists between pelvic rotation
      and hip flexion in standing subjects. RELEVANCE: Hip flexion, while standing, is
      a common element of many functional activities. Knowledge of the pelvic
      contribution increases our understanding of hip and lumbar spine motion during
      standing activities.

PMID- 11832266
TI  - Evaluation of triceps surae muscle length and resistance to passive lengthening
      in patients with acquired brain injury.
AB  - OBJECTIVE: To examine changes in muscle length and resistance to passive
      lengthening in the triceps surae muscles in patients with recently acquired brain
      injury. BACKGROUND: Increased passive resistance in the triceps surae muscles is
      common following acquired brain injury. Adaptive shortening secondary to relative
      immobility, and increased stiffness due to rheologic changes within the musculo
      tendinous unit, may be exacerbated by plantarflexor muscle overactivity related
      to the brain injury itself. DESIGN: Three variables representing resistance to
      passive lengthening and soleus muscle length were compared between subjects with
      recent brain injury and age matched normal controls. Comparison between limbs was
      made for subjects with unilateral neurological impairment. METHODS: Slow passive
      dorsiflexion stretches were performed using a computer controlled dynamometer.
      Muscle stiffness in the initial and latter portion of the range, and the angles
      achieved at torques of 5 and 10 N m were determined from torque-angle curves.
      Maximal ankle dorsiflexion with the knee flexed was considered to reflect soleus
      muscle length. RESULTS: Significant differences were demonstrated for all
      variables, except passive stiffness near the end of available range. The limb
      ipsilateral to unilateral brain injury differed from control limbs in that
      significantly less passive range of dorsiflexion was available and initial
      resistance to passive stretch was significantly less. CONCLUSIONS: The reduction
      in soleus muscle length evident in subjects with recent acquired brain injury,
      even in neurologically unaffected limbs, may reflect the influence of relative
      immobility. Although plantarflexor muscle overactivity was found to be associated
      with increased resistance to slow passive stretch, the mechanism was unable to be
      elucidated from these data. The limb ipsilateral to unilateral neurological
      impairment cannot be considered to be a 'normal' control for comparative
      purposes. RELEVANCE: Adaptive shortening and increased resistance to passive
      lengthening limit active ankle dorsiflexion, and alter ankle biomechanics. Tonic
      muscle overactivity has the potential to exacerbate these changes. Prophylactic
      management of inappropriate muscle activity and maintenance of muscle length may
      facilitate the achievement of rehabilitation goals and reduce subsequent
      disability following acquired brain injury.

PMID- 11832267
TI  - Comparison of angular lumbar spine and pelvis kinematics during treadmill and
      overground locomotion.
AB  - OBJECTIVE: To determine the differences between angular oscillation curves of the
      lumbar spine and pelvis during walkway and treadmill ambulation. DESIGN: An in
      vivo observation of walking in overground and treadmill conditions. BACKGROUND:
      Angular movements of the lumbar spine and pelvis have been obtained during
      overground and treadmill walking. No data are available to indicate whether
      lumbar spine treadmill findings may be compared or generalized to overground
      readings. METHODS: Nine male subjects walked at their natural cadence along an 8
      m walkway positioned over a motorized treadmill. During each of 20 walking
      trials, kinematic data of one full gait cycle were collected in the middle
      segment of the walkway. Following the overground readings the walkway was removed
      and treadmill recordings were taken at the subjects' preferred walking speed and
      at an imposed speed of 1.25 m/s. Movement patterns and maximum oscillation angles
      were calculated in each plane. RESULTS: Cross-correlation values of pairwise
      comparisons demonstrated almost comparable movement patterns between walking
      conditions (r > or =0.891; p<0.001) except for the movement in the sagittal plane
      (r=0.642, p<0.01). ANOVA for repeated measures revealed significant (p<0.05)
      differences in the gait cycle duration as well as reductions in oscillation
      amplitudes of the upper lumbar region and the pelvis in both the frontal and
      transverse plane during treadmill walking compared to walkway locomotion.
      CONCLUSIONS: Statistically significant differences exist for some angular lumbar
      spine movement parameters between walkway and treadmill locomotion. RELEVANCE:
      The observed differences between overground and treadmill locomotion should be
      taken in account when treadmill-based lumbar spine and pelvis kinematics want to
      be extended or compared to overground recordings.

PMID- 11832268
TI  - A sequence of two rotations--50 degrees torso flexion followed by +/-120 degrees
      of head axial rotation--was monitored using (essentially) goniometers and
      simultaneously measured by Euler XZY an YZX decompositions of marker data from an
      electromagnetic system (Flock of Birds).

PMID- 11832269
TI  - Plumbing the depths of PUFA biosynthesis: a novel polyketide synthase-like
      pathway from marine organisms.
AB  - Polyunsaturated fatty acids (PUFAs) are involved in determining the biophysical
      properties of membranes as well as being precursors for signalling molecules.
      C(20+) PUFA biosynthesis is catalysed by sequential desaturation and fatty acyl
      elongation reactions. This aerobic biosynthetic pathway was thought to be
      taxonomically conserved, but an alternative anaerobic pathway for the
      biosynthesis of polyunsaturated fatty acids is now known to exist that is
      analogous to polyketide synthases (PKS). These novel PKS genes could be used to
      direct the synthesis of PUFAs in heterologous hosts, as well as exploiting the
      combinatorial chemistry of PKSs to make unusual fatty acids.

PMID- 11832270
TI  - Protein phosphorylation in and around signal transduction.
AB  - Plant Protein Phosphorylation, 12-15 September 2001, Vienna, Austria.

PMID- 11832275
TI  - Colour patterns in vegetative parts of plants deserve more research attention.

PMID- 11832276
TI  - Fitness costs of induced resistance: emerging experimental support for a slippery
      concept.
AB  - Fitness costs can explain the evolution and maintenance of induced resistance in
      plants. However, the methods currently used to gather evidence for such costs do
      not allow decreases in fitness to be cleanly attributed to individual traits
      responsible for induced resistance, because the studies are plagued by multiple
      confounding responses. Reproductive performance provides an overview of
      physiological performance and is thus a useful currency to understand the
      function of induced responses. Integrated molecular, physiological and ecological
      studies are needed to identify the mechanisms responsible for the decrease in
      fitness and to evaluate fully the usefulness of the cost paradigm.

PMID- 11832277
TI  - Balancing selection favors guarding resistance proteins.
AB  - The co-evolutionary arms race model for plant-pathogen interactions implies that
      resistance (R) genes are relatively young and monomorphic. However, recent
      reports show R gene longevity and co-existence of multiple R genes in natural
      populations. This indicates that R genes are maintained by balancing selection,
      which occurs when loss of the matching avirulence (Avr) gene in the pathogen is
      associated with reduced virulence. We reason that balancing selection favors R
      proteins that function as guards, monitoring changes in the virulence target
      mediated by the Avr factor, rather than recognizing the Avr factor itself.
      Indeed, the available experimental data support the notion that guarding is
      prevalent in gene-for-gene interactions.

PMID- 11832278
TI  - Protein import into cyanelles.
AB  - "Cyanelles" are peptidoglycan-armored plastids of glaucocystophyte algae with
      close morphological and biochemical resemblance to endosymbiotic cyanobacteria.
      Genome sequencing and phylogenetic analysis have placed cyanelles on the earliest
      branch of phototrophic eukaryotes after the singular primary endosymbiotic event,
      the closest relatives to cyanobacteria among extant plastids. This model is
      supported by similar mechanisms for the targeting of nucleus-encoded cyanelle and
      chloroplast precursor proteins whose genes were transferred to the nucleus after
      the endosymbiotic event. As in chloroplasts, a prokaryote-type Sec preprotein
      translocase is shown to operate in cyanelle thylakoid membranes.

PMID- 11832279
TI  - Peptides: new signalling molecules in plants.
AB  - For many years, our insight into intercellular signalling in plants was based
      upon our knowledge of the so-called five classical plant hormones--auxin,
      cytokinin, ethylene, gibberellin and abscisic acid. However, biochemical and
      genetic studies have identified peptides that play crucial roles in plant growth
      and development, including defence mechanisms in response to wounding by pests,
      the control of cell division and expansion, and pollen self-incompatibility.
      Genome sequencing has revealed many predicted peptide-encoding genes and possible
      receptors, and a major challenge of the post-genomics era is to determine the
      function of these molecules.

PMID- 11832280
TI  - Milestones in chloroplast genetic engineering: an environmentally friendly era in
      biotechnology.
AB  - Chloroplast genomes defied the laws of Mendelian inheritance at the dawn of plant
      genetics, and continue to defy the mainstream approach to biotechnology, leading
      the field in an environmentally friendly direction. Recent success in engineering
      the chloroplast genome for resistance to herbicides, insects, disease and
      drought, and for production of biopharmaceuticals, has opened the door to a new
      era in biotechnology. The successful engineering of tomato chromoplasts for high
      level transgene expression in fruits, coupled to hyper-expression of vaccine
      antigens, and the use of plant-derived antibiotic-free selectable markers, augur
      well for oral delivery of edible vaccines and biopharmaceuticals that are
      currently beyond the reach of those who need them most.

PMID- 11832281
TI  - Indian plant biology enters the biotechnology era.

PMID- 11832284
TI  - Folic acid antagonism of sulfa drug treatments.

PMID- 11832285
TI  - Schistosomiasis immunology, epidemiology and diagnosis.

PMID- 11832286
TI  - Genomics, pathogenesis and control of infection with protozoan parasites.

PMID- 11832287
TI  - Ectoparasites: recent advances in control.

PMID- 11832288
TI  - Developing worms need the host immune system.

PMID- 11832292
TI  - On the release of malaria merozoites.

PMID- 11832293
TI  - Controlling epidemic sleeping sickness.

PMID- 11832294
TI  - Vaccines, enzymes and malaria.

PMID- 11832295
TI  - How do host immune responses affect nematode infections?
AB  - Host immune responses limit, and in some instances eliminate, nematode
      infections. There is considerable interest in enhancing these natural processes
      by the use of antinematode vaccines to achieve control of infection or disease.
      How nematodes are damaged is unclear. Worms might be damaged directly by effector
      cells and molecules of the immune system. Alternatively, they might be damaged by
      the physiological stress of their efforts to resist attack. Separating these
      possibilities could have important implications for approaches to the control of
      nematode infections and the disease that they cause.

PMID- 11832296
TI  - Neospora caninum and Hammondia heydorni are separate species/organisms.
AB  - Neospora caninum and Hammondia heydorni are two coccidian parasites with
      morphologically similar oocysts in canine feces. It was recently proposed that
      they are one species. In this paper, we review the biology and morphology of
      these parasites and present evidence that N. caninum and H. heydorni are separate
      species.

PMID- 11832297
TI  - Tools from ecology: useful for evaluating infection risk models?
AB  - Despite the increasing number of models to predict infection risk for a range of
      diseases, the assessment of their spatial limits, predictive performance and
      practical application are not widely undertaken. Using the example of Schistosoma
      haematobium in Africa, this article illustrates how ecozonation and receiver
      operator characteristic analysis can help to assess the usefulness of available
      models objectively.

PMID- 11832298
TI  - Evolutionary studies of malaria vectors.
AB  - The rationales given for studies of the population genetics of vectors are
      usually: (1) to predict the spread of genes, such as genes conferring insecticide
      resistance or possibly refractoriness to parasites and (2) to reveal novel
      insights into the epidemiology and transmission of vector-borne disease. The
      successful genetic transformation of mosquitoes has highlighted the need for a
      critical assessment of the rapidly accumulating body of data on the population
      genetics of malaria vectors. This article assesses how successful molecular
      genetic techniques have been in revealing new population patterns.

PMID- 11832299
TI  - How to succeed in parasitic life without sex? Asking Leishmania.
AB  - Eukaryotes use sexual recombination to achieve innovation and adaptation to a
      changing environment, a mechanism that is exceptional in Leishmania. It is
      postulated that asexual mechanisms contribute efficiently to parasite fitness and
      that sexual recombination would not be necessary for the production of a large
      repertoire of genotypes. The model discussed in this review used a major
      Leishmania glycoprotein, gp63, which is involved in host-parasite relationships.
      Mitotic recombination, which occurs between and within tandem repeats, amplifies
      genes and generates genotypic diversity. The resulting variation in the protein
      sequence is concentrated in surface domains, in regions spanning T-cell epitopes
      and B-cell epitopes and might allow immune escape.

PMID- 11832306
TI  - Goals for benign prostatic hyperplasia therapy.

PMID- 11832307
TI  - Are all alpha-blockers created equal? An update.
AB  - alpha-Receptor blockers, used to treat lower urinary tract symptoms, exert
      effects on areas of the body other than the prostate where alpha-receptors are
      located, including the blood vessels and the central nervous system. alpha
      Receptors in the central and peripheral nervous system may be involved in bladder
      activation. alpha(1a)-Receptors are the appropriate target in men with
      obstructive symptoms, although alpha(1d)-receptors may also be important in
      patients with irritative symptoms. There is conflicting evidence about the
      selectivity of alpha-blockers. Clinical trials of these agents do not necessarily
      reflect results observed in animal and laboratory studies on uroselectivity. The
      few published comparator studies of alpha-blockers indicate similar efficacies,
      although side-effect profiles differ somewhat. Randomized, controlled studies of
      different alpha-blockers with sufficient power to detect differences in side
      effects between agents are needed.

PMID- 11832308
TI  - Quality of life and alpha-blocker therapy: an important consideration for both
      the patient and the physician.
AB  - Symptom severity and the impact of lower urinary tract symptoms (LUTS) on quality
      of life (QOL) are the usual reasons that patients with benign prostatic
      hyperplasia (BPH) seek medical care. Various questionnaires have been developed
      to assess symptom severity and to gauge the impact of these symptoms on QOL.
      These instruments have been validated in studies and are used to compare agents
      used to treat LUTS in patients with BPH. Studies have shown that as the severity
      of LUTS increases, so does the impact on a patient's QOL. Tools have also been
      developed to assess sexual function in patients with BPH who frequently manifest
      erectile dysfunction. Treatment of LUTS in patients with BPH should be evaluated
      for the effect on symptom severity, QOL, and sexual function.

PMID- 11832309
TI  - Rationale and assessment of minimally invasive approaches to benign prostatic
      hyperplasia therapy.
AB  - Benign prostatic hyperplasia affects quality of life, with most patients
      complaining of symptoms related to urination. For this reason, successful
      treatments can be defined by (1) their effect on lower urinary tract symptoms,
      (2) their impact on quality of life, and (3) their ability to unobstruct the flow
      of urine through the prostate. Minimally invasive therapy (MIT), which includes
      transurethral microwave thermotherapy, water-induced thermotherapy, interstitial
      devices (eg, transurethral needle ablation), and interstitial laser treatments,
      offers physicians and their patients cost-effective alternatives for achieving a
      substantially improved quality of life at an acceptable level of risk. Evidence
      based medicine indicates that MIT is safe and achieves significant symptomatic
      improvement. Compared with long-term medical management, minimally invasive
      procedures offer effective, well-tolerated 1-time intervention with lasting
      effects that can be achieved on an outpatient basis. This article reviews the
      options for MIT.

PMID- 11832310
TI  - Scapula fractures.
AB  - Scapula fractures are relatively rare fractures which are typically a result of
      high energy trauma. Associated multisystemic injuries, therefore, occur with a
      high frequency. The management of scapula fractures has historically been
      nonoperative, perhaps in part due to the paucity of information regarding
      outcomes, combined with a relative unfamiliarity with treating these injuries. It
      is likely, however, that intraarticular fractures, and certain other highly
      displaced variants, have a better outcome when treated operatively. A well
      conceived diagnostic work-up and a properly executed plan of rehabilitation are
      requisite.

PMID- 11832311
TI  - Management of the smashed distal humerus.
AB  - The purpose of this article is to present a principle-based approach to treating
      the smashed distal humerus. These injuries are challenging to even the most
      experienced surgeons. The four goals, in order of priority, are soft tissue
      healing without infection, restoration of diaphyseal bone stock, union between
      the distal fragments and the shaft, and a stable and mobile articulation.

PMID- 11832312
TI  - Wrist fractures.
AB  - The benefits of a well-reduced and well-healed wrist fracture are predictable.
      This knowledge has prompted the development of myriad treatment methods and
      fixation devices. The choice of open versus closed reduction and the devices used
      to maintain that reduction could most often be determined with a well-defined and
      reproducible closed reduction maneuver. With this maneuver, the integrity of the
      critical volar ulnar corner of the radius is determined as is articular stepoff,
      metaphyseal comminution, and distal radionular joint (DRUJ) stability.
      Reconstruction of the subluxed or dislocated DRUJ starts with the reduction of
      the radius, frequently obviating the need to address fractures involving the
      ulnar head and styloid. Most importantly, the results of treatment reflect
      surgical decision over the fixation method.

PMID- 11832313
TI  - High-energy pelvic ring disruptions.
AB  - High energy pelvic ring disruptions are associated with numerous primary organ
      system injuries. Early, accurate pelvic reduction and stable fixation optimize
      patient outcome. A variety of fixation techniques have been advocated. A
      multispecialty team approach is advantageous when managing these patients and
      their pelvic injuries.

PMID- 11832314
TI  - Associated injuries complicating the management of acetabular fractures: review
      and case studies.
AB  - The treatment of acetabular fractures has evolved considerably in the past three
      decades. Associated injuries to the femoral head, proximal femur, or femoral
      shaft can complicate the initial management of the acetabular fracture, and
      mandate a careful treatment strategy for optimal treatment of both the acetabular
      fracture and associated injury. These injuries may have a large impact on the
      clinical outcome. The surgeon must consider surgical approaches, timing, and
      alternative modes of fixation. A discussion with case illustrations is provided.

PMID- 11832315
TI  - Femoral neck fractures.
AB  - Femoral neck fractures in the geriatric patient continue to represent a
      therapeutic challenge. Despite advances in surgical techniques and medical care,
      the risk of nonunion and osteonecrosis after fixation have not changed
      appreciably in the last 50 years. Considerable debate continues to occur with
      respect to the relative merits of internal fixation versus arthroplasty. The
      relative benefits and complications of unipolar and bipolar hemiarthroplasty, as
      well as total hip replacement, continue to be poorly understood. The next decade
      will bring advances in the prevention and treatment of osteoporosis that may
      finally decrease the incidence of these fractures. Advances in the use of bone
      graft substitutes may finally improve the outcome of internal fixation.

PMID- 11832316
TI  - Subtrochanteric femur fractures.
AB  - Fractures in the subtrochanteric zone of the proximal femur present complex
      treatment challenges. These treatment difficulties are related to the anatomic
      and biomechanic features that are unique to this area. These fractures occur in
      older patients from low-energy trauma and in younger patients with high-energy
      trauma, with separate diagnostic and treatment significance. Intramedullary
      fixation with standard centromedullary nails, as well as cephalomedullary nails,
      are commonly employed as fixation methods to treat this fracture. The techniques
      and results of this will be reviewed.

PMID- 11832317
TI  - Complicated femoral shaft fractures.
AB  - The treatment of femoral shaft fractures has become safe and reproducible since
      the advent of popularization of intramedullary nailing, however, many femoral
      shaft fractures are complicated by associated fractures, extensive comminution,
      extensive contamination, and arterial injury compartmental syndrome. Other
      conditions associated with the use of femoral nailing include femora nonunions,
      broken hardware, acute fractures with prior implants, and infections. The
      management of these complex femoral shaft fractures demands special techniques
      for successful outcome.

PMID- 11832318
TI  - Periprosthetic fractures of the femur.
AB  - Periprosthetic fractures of the femur represent a heterogeneous and challenging
      problem for the orthopedic surgeon. The incidence of these fractures is
      dramatically increasing, as there are more and more patients with aging total
      joint replacements. The fractures may occur as the result of a traumatic event,
      but more often are the result of minor trauma spontaneous fracture, and they are
      frequently associated with preexisting, sometimes neglected, problems with the
      associated joint replacement.

PMID- 11832319
TI  - Distal femur fractures with complex articular involvement: management by
      articular exposure and submuscular fixation.
AB  - The A.O./O.T.A. C3 distal femur fracture is characterized by complex articular
      involvement and is often accompanied by a very short distal femur segment, small
      osteochondral fragments, and high-energy soft tissue disruption. Current fixation
      strategies do not provide for optimal visualization/reduction of the articular
      surface in conjunction with stable fixation of the distal femoral block.
      Malunion, loss of fixation, need for supplemental fixation, and need for bone
      grafting is common in the treatment of the C3 distal femur fracture. The
      transarticular percutaneous osteosynthesis technique, popularized by Krettek, et
      al, utilizes a lateral peripatellar approach for optimal articular visualization
      and submuscular fixation for minimal devitalization. In this article, its use is
      described, as well as reduction and fixation strategies for the articular
      surface.

PMID- 11832320
TI  - Open reduction and internal fixation of high-energy tibial plateau fractures.
AB  - Proximal tibial articular fractures are caused by a variety of mechanisms and are
      characterized by numerous distinct fracture patterns. Surgical treatment for
      other than minimally displaced or nondisplaced fractures is recommended to
      restore joint congruity and limb alignment, and to allow early, stable, knee
      motion.

PMID- 11832321
TI  - Hybrid external fixation for tibial plateau fractures: clinical and biomechanical
      correlation.
AB  - The biomechanical data support the use of tensioned wire fixation to stabilize
      complex fractures of the proximal tibia. The authors will show that the stability
      of a four-wire construct is comparable to the gold standard of dual plating
      internal fixation techniques. Using these techniques, many recent investigators
      have demonstrated improved clinical results, with average knee scores for most
      patients ranging from 85 to 90.

PMID- 11832322
TI  - High-energy tibial shaft fractures.
AB  - High-energy tibial fractures are common injuries that are managed by most
      practicing orthopaedic surgeons. Many methods of treatment are available. This
      article reviews the options for skeletal stabilization, the risks and benefits of
      each, and the necessary concepts that effect outcome.

PMID- 11832323
TI  - Pilon fractures: assessment and treatment.
AB  - The treatment of high-energy intra-articular fractures of the tibial plafond
      involves many potential complications. A protocol has been developed. This
      protocol recognizes the importance of the surrounding soft tissues and is based
      on sound principles and thorough clinical experience. This article discusses this
      protocol and its use and explains why it is now more widely accepted.

PMID- 11832324
TI  - Fractures of the talar neck.
AB  - Fractures of the talus have been described for 400 years. This article reviews
      the history of this injury and its treatment. It also discusses the modern
      results and complications involved with the injury and treatment.

PMID- 11832325
TI  - Fractures of the calcaneus.
AB  - Displaced fractures of the calcaneous are relatively common injuries that remain
      a treatment enigma. Virtually all aspects of the management of calcaneal
      fractures are a source of debate. Contemporary imaging, reduction, and fixation
      techniques attempt to improve the long term results of these injuries. The
      complex fracture fragments displace in predictable patterns. Meticulous surgical
      technique, restoration of extra- and intra-articular anatomy, and obtaining rigid
      fracture fixation are critical to obtaining satisfactory operative results. This
      article extensively reviews the controversies and summarizes the current opinions
      in the management of displaced calcaneal fractures.

PMID- 11832326
TI  - Focus on "EGF receptor downregulation depends on a trafficking motif in the
      distal tyrosine kinase domain".

PMID- 11832327
TI  - EGF receptor downregulation depends on a trafficking motif in the distal tyrosine
      kinase domain.
AB  - On binding to its receptor, epidermal growth factor (EGF) initiates a cascade of
      events leading to cell proliferation or differentiation. In addition, the EGF
      receptor itself is downregulated to attenuate mitogenic signaling. Downregulation
      occurs through trafficking of receptors to lysosomes, culminating in proteolytic
      destruction of both the receptor and ligand; however, endocytic sorting
      mechanisms that underlie lysosomal targeting remain obscure. The goal of this
      study was to explore one aspect of the molecular basis for ligand-induced
      lysosomal targeting and degradation of EGF receptors. In this study, we identify
      a tyrosine-leucine motif ((954)YLVI) that is essential for transit of ligand
      receptor complexes to lysosomes. When this motif is mutated, HEK 293 cells
      expressing the mutant receptors demonstrate impaired lysosomal targeting and
      downregulation compared with wild-type receptors. (954)YLVI is highly conserved
      among EGF receptors from various mammalian and invertebrate species and is
      critical for receptor downregulation. We propose that (954)YLVI works in concert
      with at least two additional regions within the EGF receptor cytoplasmic domain
      that are essential for efficiently targeting ligand-receptor complexes to the
      lysosome.

PMID- 11832328
TI  - Vasopressin-mediated mitogenic signaling in intestinal epithelial cells.
AB  - The role of G protein-coupled receptors and their ligands in intestinal
      epithelial cell signaling and proliferation is poorly understood. Here, we
      demonstrate that arginine vasopressin (AVP) induces multiple intracellular signal
      transduction pathways in rat intestinal epithelial IEC-18 cells via a V(1A)
      receptor. Addition of AVP to these cells induces a rapid and transient increase
      in cytosolic Ca(2+) concentration and promotes protein kinase D (PKD) activation
      through a protein kinase C (PKC)-dependent pathway, as revealed by in vitro
      kinase assays and immunoblotting with an antibody that recognizes
      autophosphorylated PKD at Ser(916). AVP also stimulates the tyrosine
      phosphorylation of the nonreceptor tyrosine kinase proline-rich tyrosine kinase 2
      (Pyk2) and promotes Src family kinase phosphorylation at Tyr(418), indicative of
      Src activation. AVP induces extracellular signal-related kinase (ERK)-1
      (p44(mapk)) and ERK-2 (p42(mapk)) activation, a response prevented by treatment
      with mitogen-activated protein kinase kinase (MEK) inhibitors (PD-98059 and U
      0126), specific PKC inhibitors (GF-I and Ro-31-8220), depletion of Ca(2+) (EGTA
      and thapsigargin), selective epidermal growth factor receptor (EGFR) tyrosine
      kinase inhibitors (tyrphostin AG-1478, compound 56), or the selective Src family
      kinase inhibitor PP-2. Furthermore, AVP acts as a potent growth factor for IEC-18
      cells, inducing DNA synthesis and cell proliferation through ERK-, Ca(2+)-, PKC-,
      EGFR tyrosine kinase-, and Src-dependent pathways.

PMID- 11832330
TI  - Ca(2+)-activated K+ channel inhibition by reactive oxygen species.
AB  - We studied the effect of H(2)O(2) on the gating behavior of large-conductance
      Ca(2+)-sensitive voltage-dependent K(+) (K(V,Ca)) channels. We recorded potassium
      currents from single skeletal muscle channels incorporated into bilayers or using
      macropatches of Xenopus laevis oocytes membranes expressing the human Slowpoke
      (hSlo) alpha-subunit. Exposure of the intracellular side of K(V,Ca) channels to
      H(2)O(2) (4-23 mM) leads to a time-dependent decrease of the open probability
      (P(o)) without affecting the unitary conductance. H(2)O(2) did not affect channel
      activity when added to the extracellular side. These results provide evidence for
      an intracellular site(s) of H(2)O(2) action. Desferrioxamine (60 microM) and
      cysteine (1 mM) completely inhibited the effect of H(2)O(2), indicating that the
      decrease in P(o) was mediated by hydroxyl radicals. The reducing agent
      dithiothreitol (DTT) could not fully reverse the effect of H(2)O(2). However, DTT
      did completely reverse the decrease in P(o) induced by the oxidizing agent 5,5'
      dithio-bis-(2-nitrobenzoic acid). The incomplete recovery of K(V,Ca) channel
      activity promoted by DTT suggests that H(2)O(2) treatment must be modifying other
      amino acid residues, e.g., as methionine or tryptophan, besides cysteine. Noise
      analysis of macroscopic currents in Xenopus oocytes expressing hSlo channels
      showed that H(2)O(2) induced a decrease in current mediated by a decrease both in
      the number of active channels and P(o).

PMID- 11832331
TI  - Placental ceruloplasmin homolog is regulated by iron and copper and is implicated
      in iron metabolism.
AB  - We previously reported an endogenous, membrane-bound Cu oxidase with homology to
      ceruloplasmin in BeWo cells, a placental choriocarcinoma cell line. In this
      previous study, ceruloplasmin immunoreactivity was localized to the perinuclear
      region and non-brush-border membranes. Here, we show that azide-sensitive oxidase
      activity is enriched in the same fractions, correlating subcellular localization
      of enzyme activity with ceruloplasmin immunoreactivity. Expression of the
      placental Cu oxidase is inversely proportional to Fe status and directly
      proportional to Cu status at enzyme and protein levels. To identify a role for
      the Cu oxidase, cells were exposed to (59)Fe-transferrin for 18 h in an
      environment of 20% O(2) or 5% O(2). At 5% O(2), Cu-deficient cells retain
      significantly more (59)Fe than control cells. This excess in (59)Fe accumulation
      is caused by a significant decrease in (59)Fe release. These results indicate
      that downregulation of the placental Cu oxidase in BeWo cells impairs Fe release.
      This effect is only apparent in an environment of limited O(2).

PMID- 11832329
TI  - 220- and 130-kDa MLCKs have distinct tissue distributions and intracellular
      localization patterns.
AB  - To better understand the distinct functional roles of the 220- and 130-kDa forms
      of myosin light chain kinase (MLCK), expression and intracellular localization
      were determined during development and in adult mouse tissues. Northern blot,
      Western blot, and histochemical studies show that the 220-kDa MLCK is widely
      expressed during development as well as in several adult smooth muscle and
      nonmuscle tissues. The 130-kDa MLCK is highly expressed in all adult tissues
      examined and is also detectable during embryonic development. Colocalization
      studies examining the distribution of 130- and 220-kDa mouse MLCKs revealed that
      the 130-kDa MLCK colocalizes with nonmuscle myosin IIA but not with myosin IIB or
      F-actin. In contrast, the 220-kDa MLCK did not colocalize with either nonmuscle
      myosin II isoform but instead colocalizes with thick interconnected bundles of F
      actin. These results suggest that in vivo, the physiological functions of the 220
      and 130-kDa MLCKs are likely to be regulated by their intracellular trafficking
      and distribution.

PMID- 11832332
TI  - Mechanotransduction through the cytoskeleton.
AB  - We constructed a model cytoskeleton to investigate the proposal that this
      interconnected filamentous structure can act as a mechano- and signal transducer.
      The model cytoskeleton is composed of rigid rods representing actin filaments,
      which are connected with springs representing cross-linker molecules. The entire
      mesh is placed in viscous cytoplasm. The model eukaryotic cell is submitted to
      either shock wave-like or periodic mechanical perturbations at its membrane. We
      calculated the efficiency of this network to transmit energy to the nuclear wall
      as a function of cross-linker stiffness, cytoplasmic viscosity, and external
      stimulation frequency. We found that the cytoskeleton behaves as a tunable band
      filter: for given linker molecules, energy transmission peaks in a narrow range
      of stimulation frequencies. Most of the normal modes of the network are spread
      over the same frequency range. Outside this range, signals are practically unable
      to reach their destination. Changing the cellular ratios of linker molecules with
      different elastic characteristics can control the allowable frequency range and,
      with it, the efficiency of mechanotransduction.

PMID- 11832333
TI  - Age-dependent regulation of rat intestinal type IIb sodium-phosphate
      cotransporter by 1,25-(OH)(2) vitamin D(3).
AB  - The current studies were designed to characterize type IIb sodium-inorganic
      phosphate (P(i)) cotransporter (NaP(i)-IIb) expression and to assess the effect
      of 1,25-(OH)(2) vitamin D(3) on NaP(i)-IIb gene expression during rat ontogeny.
      Sodium-dependent P(i) absorption by intestinal brush-border membrane vesicles
      (BBMVs) decreased with age, and NaP(i)-IIb gene expression also decreased
      proportionally with age. 1,25-(OH)(2) vitamin D(3) treatment increased intestinal
      BBMV P(i) absorption by approximately 2.5-fold in suckling rats and by
      approximately 2.1-fold in adult rats. 1,25-(OH)(2) vitamin D(3) treatment also
      increased NaP(i)-IIb mRNA abundance by approximately 2-fold in 14-day-old rats
      but had no effect on mRNA expression in adults. Furthermore, in rat intestinal
      epithelial (RIE) cells, 1,25-(OH)(2) vitamin D(3) increased NaP(i)-IIb mRNA
      abundance, an effect that was abolished by actinomycin D. Additionally, human
      NaP(i)-IIb gene promoter activity in transiently transfected RIE cells showed
      approximately 1.6-fold increase after 1,25-(OH)(2) vitamin D(3) treatment. In
      conclusion, we demonstrate that the age-related decrease in intestinal sodium
      dependent P(i) absorption correlates with decreased NaP(i)-IIb mRNA expression.
      Our data also suggest that the effect of 1,25-(OH)(2) vitamin D(3) on NaP(i)-IIb
      expression is at least partially mediated by gene transcription in suckling rats.

PMID- 11832334
TI  - sgk: an essential convergence point for peptide and steroid hormone regulation of
      ENaC-mediated Na+ transport.
AB  - To study the role of sgk (serum, glucocorticoid-induced kinase) in hormonal
      regulation of Na+ transport mediated by the epithelial Na+ channel (ENaC), clonal
      cell lines stably expressing human sgk, an S422A sgk mutant, or a D222A sgk
      mutant were created in the background of the A6 model renal epithelial cell line.
      Expression of normal sgk results in a 3.5-fold enhancement of basal transport and
      potentiation of the natriferic response to antidiuretic hormone (ADH).
      Transfection of a S422A mutant form of sgk, which cannot be phosphorylated by
      phosphatidylinositol-dependent kinase (PDK)-2, results in a cell line that is
      indistinguishable from the parent line in basal and hormone-stimulated Na+
      transport. The D222A sgk mutant, which lacks kinase activity, functions as a
      dominant-negative mutant inhibiting basal as well as peptide- and steroid hormone
      stimulated Na+ transport. Thus sgk activity is necessary for ENaC-mediated Na+
      transport. Phosphorylation and activation by PDK-2 are necessary for sgk
      stimulation of ENaC. Expression of normal sgk over endogenous levels results in a
      potentiated natriferic response to ADH, suggesting that the enzyme is a rate
      limiting step for the hormone response. In contrast, sgk does not appear to be
      the rate-limiting step for the cellular response to aldosterone or insulin.

PMID- 11832335
TI  - Role of gap junctions in fluid secretion of lacrimal glands.
AB  - In glands such as the liver and pancreas, gap junctions containing connexin 26
      and 32 (Cx26 and Cx32, respectively) couple the secretory cells. Uncoupling these
      junctions compromises the secretory function of these glands. Lacrimal glands
      also contain extensive arrays of gap junctions consisting of Cx26 and Cx32. We
      wanted to determine the role of these junctions in fluid secretion. In Cx32
      deficient mice, immunocytochemistry showed that, in the male lacrimal gland, the
      remaining Cx26 was found evenly distributed in the membrane whereas there was
      little in the membranes of female glands. Western blot analysis of Cx26 showed
      that female Cx32-deficient mice expressed Cx26. Patch-clamp analyses of acinar
      cell coupling showed that the cell pairs from male glands were coupled whereas
      those from female glands were not. Stimulated fluid production by the glands from
      Cx32-deficient mice was abnormally low in female glands compared with controls at
      low topical doses of carbachol. The protein secretory response to different doses
      of carbachol was the same in all animals. These data suggest that gap junctions
      are essential for optimal fluid secretion in lacrimal glands.

PMID- 11832336
TI  - PKA-dependent activation of PDE3A and PDE4 and inhibition of adenylyl cyclase
      V/VI in smooth muscle.
AB  - Regulation of adenylyl cyclase type V/VI and cAMP-specific, cGMP-inhibited
      phosphodiesterase (PDE) 3 and cAMP-specific PDE4 by cAMP-dependent protein kinase
      (PKA) and cGMP-dependent protein kinase (PKG) was examined in gastric smooth
      muscle cells. Expression of PDE3A but not PDE3B was demonstrated by RT-PCR and
      Western blot. Basal PDE3 and PDE4 activities were present in a ratio of 2:1.
      Forskolin, isoproterenol, and the PKA activator 5,6-dichloro-1-beta-D
      ribofuranosyl benzimidazole 3',5'-cyclic monophosphate, SP-isomer, stimulated
      PDE3A phosphorylation and both PDE3A and PDE4 activities. Phosphorylation of
      PDE3A and activation of PDE3A and PDE4 were blocked by the PKA inhibitors
      [protein kinase inhibitor (PKI) and H-89] but not by the PKG inhibitor (KT-5823).
      Sodium nitroprusside inhibited PDE3 activity and augmented forskolin- and
      isoproterenol-stimulated cAMP levels; PDE3 inhibition was reversed by blockade of
      cGMP synthesis. Forskolin stimulated adenylyl cyclase phosphorylation and
      activity; PKI blocked phosphorylation and enhanced activity. Stimulation of cAMP
      and inhibition of inositol 1,4,5-trisphosphate-induced Ca(2+) release and muscle
      contraction by isoproterenol were augmented additively by PDE3 and PDE4
      inhibitors. The results indicate that PKA regulates cAMP levels in smooth muscle
      via stimulatory phosphorylation of PDE3A and PDE4 and inhibitory phosphorylation
      of adenylyl cyclase type V/VI. Concurrent generation of cGMP inhibits PDE3
      activity and augments cAMP levels.

PMID- 11832337
TI  - Functional overload increases beta-MHC promoter activity in rodent fast muscle
      via the proximal MCAT (betae3) site.
AB  - Functional overload (OL) of the rat plantaris muscle by the removal of
      synergistic muscles induces a shift in the myosin heavy chain (MHC) isoform
      expression profile from the fast isoforms toward the slow type I, or, beta-MHC
      isoform. Different length rat beta-MHC promoters were linked to a firefly
      luciferase reporter gene and injected in control and OL plantaris muscles.
      Reporter activities of -3,500, -914, -408, and -215 bp promoters increased in
      response to 1 wk of OL. The smallest -171 bp promoter was not responsive to OL.
      Mutation analyses of putative regulatory elements within the -171 and -408 bp
      region were performed. The -408 bp promoters containing mutations of the betae1,
      distal muscle CAT (MCAT; betae2), CACC, or A/T-rich (GATA), were still responsive
      to OL. Only the proximal MCAT (betae3) mutation abolished the OL response. Gel
      mobility shift assays revealed a significantly higher level of complex formation
      of the betae3 probe with nuclear protein from OL plantaris compared with control
      plantaris. These results suggest that the betae3 site functions as a putative OL
      responsive element in the rat beta-MHC gene promoter.

PMID- 11832338
TI  - Transcriptional regulation of the type I myosin heavy chain promoter in inactive
      rat soleus.
AB  - Chronic muscle inactivity with spinal cord isolation (SI) decreases expression of
      slow type I myosin heavy chain (MHC) while increasing expression of the faster
      MHC isoforms, primarily IIx. The purpose of this study was to determine whether
      type I MHC downregulation in the soleus muscle of SI rats is regulated
      transcriptionally and to identify cis-acting elements or regions of the rat type
      I MHC gene promoter involved in this response. One week of SI significantly
      decreased in vivo activity of the -3500-, -408-, -299-, -215-, and -171-bp type I
      MHC promoters. The activity of all tested deletions of the type I MHC promoter,
      relative to the human skeletal alpha-actin promoter, were significantly reduced
      in the SI soleus, except activity of the -171-bp promoter, which increased.
      Mutation of the betae3 element (-214/-190 bp) in the -215- and -408-bp promoters
      and deletion of this element (-171-bp promoter) attenuated type I downregulation
      with SI. Gel mobility shift assays demonstrated a decrease in transcription
      enhancer factor-1 binding to the betae3 element with SI, despite an increase in
      total binding to this region. These results demonstrate that type I MHC
      downregulation with SI is transcriptionally regulated and suggest that
      interactions between transcription enhancer factor-1 and the betae3 element are
      likely involved in this response.

PMID- 11832339
TI  - Adenoviral gene transfer of PDGF downregulates gas gene product PDGFalphaR and
      prolongs ERK and Akt/PKB activation.
AB  - The delivery of platelet-derived growth factor (PDGF) for tissue engineering of
      skin and periodontal wounds has become an active area of interest. However,
      little is known regarding the extended effects of PDGF on cell signaling via gene
      therapy and how such an approach facilitates the exiting of cells from growth
      arrest and entry to competence required for cell cycling. We show in vitro
      expression and secretion of PDGF-AA by recombinant adenovirus encoding the PDGF-A
      gene (Ad-PDGF-A). The bioactive PDGF-AA protein released induces sustained
      downregulation of PDGFalphaR that is encoded by a growth arrest-specific (gas)
      gene. Ad-PDGF-A induces sustained phosphorylation of PDGFalphaR as well as
      prolonged phosphorylation of downstream extracellular signal-regulated kinase 1/2
      and Akt signaling pathways. Furthermore, the phosphorylation of PDGFalphaR is
      abolished by cotransducing cells with adenovirus encoding a dominant negative
      mutant of the PDGF-A gene that disrupts PDGF bioactivity. These findings
      demonstrate the prolonged effects of adenoviral delivery of PDGF and aid in the
      better understanding of sustained PDGF signaling.

PMID- 11832340
TI  - Autocrine loops with positive feedback enable context-dependent cell signaling.
AB  - We describe a mechanism for context-dependent cell signaling mediated by
      autocrine loops with positive feedback. We demonstrate that the composition of
      the extracellular medium can critically influence the intracellular signaling
      dynamics induced by extracellular stimuli. Specifically, in the epidermal growth
      factor receptor (EGFR) system, amplitude and duration of mitogen-activated
      protein kinase (MAPK) activation are modulated by the positive-feedback loop
      formed by the EGFR, the Ras-MAPK signaling pathway, and a ligand-releasing
      protease. The signaling response to a transient input is short-lived when most of
      the released ligand is lost to the cellular microenvironment by diffusion and/or
      interaction with an extracellular ligand-binding component. In contrast, the
      response is prolonged or persistent in a cell that is efficient in recapturing
      the endogenous ligand. To study functional capabilities of autocrine loops, we
      have developed a mathematical model that accounts for ligand release, transport,
      binding, and intracellular signaling. We find that context-dependent signaling
      arises as a result of dynamic interaction between the parts of an autocrine loop.
      Using the model, we can directly interpret experimental observations on context
      dependent responses of autocrine cells to ionizing radiation. In human carcinoma
      cells, MAPK signaling patterns induced by a short pulse of ionizing radiation can
      be transient or sustained, depending on cell type and composition of the
      extracellular medium. On the basis of our model, we propose that autocrine loops
      in this, and potentially other, growth factor and cytokine systems may serve as
      modules for context-dependent cell signaling.

PMID- 11832341
TI  - Hyperglycemia increases endothelial superoxide that impairs smooth muscle cell
      Na+-K+-ATPase activity.
AB  - Nitric oxide (NO) plays an important role in the control of numerous vascular
      functions including basal Na+-K+-ATPase activity in arterial tissue.
      Hyperglycemia inhibits Na+-K+-ATPase activity in rabbit aorta, in part, through
      diminished bioactivity of NO. The precise mechanism(s) for such observations,
      however, are not yet clear. The purpose of this study was to examine the role of
      superoxide in modulating NO-mediated control of Na+-K+-ATPase in response to
      hyperglycemia. Rabbit aorta incubated with hyperglycemic glucose concentrations
      (44 mM) demonstrated a 50% reduction in Na+-K+-ATPase activity that was abrogated
      by superoxide dismutase. Hyperglycemia also produced a 50% increase in steady
      state vascular superoxide measured by lucigenin-enhanced chemiluminescence that
      was closely associated with reduced Na+-K+-ATPase activity. Specifically, the
      hyperglycemia-induced increase in vascular superoxide was endothelium dependent,
      inhibited by L-arginine, and stimulated by N(omega)-nitro-L-arginine. Aldose
      reductase inhibition with zopolrestat also inhibited the hyperglycemia-induced
      increase in vascular superoxide. In each manipulation of vascular superoxide, a
      reciprocal change in Na+-K+-ATPase activity was observed. Finally, a commercially
      available preparation of Na+-K+-ATPase was inhibited by pyrogallol, a superoxide
      generator. These data suggest that hyperglycemia induces an increase in
      endothelial superoxide that inhibits the stimulatory effect of NO on vascular Na+
      K+-ATPase activity.

PMID- 11832342
TI  - Functional reconstitution of an eicosanoid-modulated Cl- channel from bovine
      tracheal smooth muscle.
AB  - We describe the biochemical properties of an eicosanoid-modulated Cl- channel and
      assess the mechanisms by which the epoxyeicosatrienoic acids (EETs) alter both
      its unitary conductance and its open probability (P(o)). After a purification
      protocol involving wheat-germ agglutinin affinity and anion-exchange
      chromatography, the proteins were sequentially inserted into liposomes, which
      were then fused into PLBs. Functional and biochemical characterization tests
      confirm that the Cl- channel is a 55-kDa glycosylated monomer with voltage- and
      Ca(2+) concentration-independent activity. 5,6- and 8,9-EET decreased the
      conductance of the native channel (control conductance: 70 +/- 5 pS in
      asymmetrical 50 mM trans/250 mM cis CsCl) in a concentration-dependent manner,
      with respective 50% inhibitory concentration values of 0.31 and 0.42 microM.
      These regioisomers similarly decreased the conductance of the purified channel
      (control conductance value: 75 +/- 5 pS in asymmetrical 50 mM trans/250 mM cis
      CsCl), which had been stripped of its native proteic and lipidic environment. On
      the other hand, 5,6- and 8,9-EETs decreased the P(o) of the native channel with
      respective 50% inhibitory concentration values of 0.27 and 0.30 microM but failed
      to alter the P(o) of the purified protein. Thus we suggest that the effects of
      these EETs on channel conductance likely result from direct interactions of EET-
      anions with the channel pore, whereas the alteration of P(o) requires a lipid
      environment of specific composition that is lost on solubilization and
      purification of the protein.

PMID- 11832343
TI  - bFGF and VEGF synergistically enhance endothelial cytoprotection via decay
      accelerating factor induction.
AB  - The complement-regulatory protein decay-accelerating factor (DAF) can be
      upregulated on endothelial cells (EC) by protein kinase C (PKC)-dependent and 
      independent pathways. We hypothesized that basic fibroblast growth factor (bFGF)
      might induce EC DAF expression, providing a cytoprotective mechanism for
      angiogenic neovessels against complement-mediated injury. Incubation of umbilical
      vein, aortic, and dermal EC with bFGF or vascular endothelial growth factor
      (VEGF) significantly increased DAF expression. Growth factor-induced EC
      proliferation was inhibited by PKC antagonists. In contrast, although PKC
      antagonists inhibited VEGF-induced DAF expression, bFGF-induced DAF was
      unaffected. Investigation of mitogen-activated kinase (MAPK) pathways also
      revealed differences, with bFGF-induced DAF dependent on p44/42 and p38 MAPK and
      VEGF requiring activation of p38 MAPK alone. Upregulation of DAF by bFGF was
      functionally relevant, reducing C3 deposition on EC after complement activation
      by 60% and resulting in marked reduction in complement-mediated EC lysis. bFGF
      and VEGF were synergistic in terms of DAF expression, resulting in enhanced
      cytoprotection. These observations reveal parallel PKC-dependent and -independent
      pathways regulating complement activation during angiogenesis. Further
      elucidation of these pathways may provide important insights into innate
      cytoprotective mechanisms in endothelium.

PMID- 11832344
TI  - Apoptosis recruits two-pore domain potassium channels used for homeostatic volume
      regulation.
AB  - Cell shrinkage is an incipient hallmark of apoptosis and is accompanied by
      potassium release that decreases the concentration of intracellular potassium and
      regulates apoptotic progression. The plasma membrane K+ channel recruited during
      apoptosis has not been characterized despite its importance as a potential
      therapeutic target. Here we provide evidence that two-pore domain K+ (K(2P))
      channels underlie K+ efflux during apoptotic volume decreases (AVD) in mouse
      embryos. These K(2P) channels are inhibited by quinine but are not blocked by an
      array of pharmacological agents that antagonize other K+ channels. The K(2P)
      channels are uniquely suited to participate in the early phases of apoptosis
      because they are not modulated by common intracellular messengers such as
      calcium, ATP, and arachidonic acid, transmembrane voltage, or the cytoskeleton. A
      K+ channel with similar biophysical properties coordinates regulatory volume
      decreases (RVD) triggered by changing osmotic conditions. We propose that K(2P)
      channels are the pathway by which K+ effluxes during AVD and RVD and that
      apoptosis co-opts mechanisms more routinely employed for homeostatic cell volume
      regulation.

PMID- 11832345
TI  - Traction fields, moments, and strain energy that cells exert on their
      surroundings.
AB  - Adherent cells exert tractions on their surroundings. These tractions can be
      measured by observing the displacements of beads embedded on a flexible gel
      substrate on which the cells are cultured. This paper presents an exact solution
      to the problem of computing the traction field from the observed displacement
      field. The solution rests on recasting the relationship between displacements and
      tractions into Fourier space, where the recovery of the traction field is
      especially simple. We present two subcases of the solution, depending on whether
      or not tractions outside the observed cell boundaries are set to be zero. The
      implementation is computationally efficient. We also give the solution for the
      traction field in a representative human airway smooth muscle cell contracted by
      treatment with histamine. Finally, we give explicit formulas for reducing the
      traction and displacement fields to contraction moments, the orientation of the
      principal axes of traction, and the strain energy imparted by the cell to the
      substrate.

PMID- 11832347
TI  - Cell prestress. II. Contribution of microtubules.
AB  - The tensegrity model hypothesizes that cytoskeleton-based microtubules (MTs)
      carry compression as they balance a portion of cell contractile stress. To test
      this hypothesis, we used traction force microscopy to measure traction at the
      interface of adhering human airway smooth muscle cells and a flexible
      polyacrylamide gel substrate. The prediction is that if MTs balance a portion of
      contractile stress, then, upon their disruption, the portion of stress balanced
      by MTs would shift to the substrate, thereby causing an increase in traction.
      Measurements were done first in maximally activated cells (10 microM histamine)
      and then again after MTs had been disrupted (1 microM colchicine). We found that
      after disruption of MTs, traction increased on average by approximately 13%.
      Because in activated cells colchicine induced neither an increase in
      intracellular Ca(2+) nor an increase in myosin light chain phosphorylation as
      shown previously, we concluded that the observed increase in traction was a
      result of load shift from MTs to the substrate. In addition, energy stored in the
      flexible substrate was calculated as work done by traction on the deformation of
      the substrate. This result was then utilized in an energetic analysis. We assumed
      that cytoskeleton-based MTs are slender elastic rods supported laterally by
      intermediate filaments and that MTs buckle as the cell contracts. Using the post
      buckling equilibrium theory of Euler struts, we found that energy stored during
      buckling of MTs was quantitatively consistent with the measured increase in
      substrate energy after disruption of MTs. This is further evidence supporting the
      idea that MTs are intracellular compression-bearing elements.

PMID- 11832346
TI  - Cell prestress. I. Stiffness and prestress are closely associated in adherent
      contractile cells.
AB  - The tensegrity hypothesis holds that the cytoskeleton is a structure whose shape
      is stabilized predominantly by the tensile stresses borne by filamentous
      structures. Accordingly, cell stiffness must increase in proportion with the
      level of the tensile stress, which is called the prestress. Here we have tested
      that prediction in adherent human airway smooth muscle (HASM) cells. Traction
      microscopy was used to measure the distribution of contractile stresses arising
      at the interface between each cell and its substrate; this distribution is called
      the traction field. Because the traction field must be balanced by tensile
      stresses within the cell body, the prestress could be computed. Cell stiffness
      (G) was measured by oscillatory magnetic twisting cytometry. As the contractile
      state of the cell was modulated with graded concentrations of relaxing or
      contracting agonists (isoproterenol or histamine, respectively), the mean
      prestress ((t)) ranged from 350 to 1,900 Pa. Over that range, cell stiffness
      increased linearly with the prestress: G (Pa) = 0.18(t) + 92. While this
      association does not necessarily preclude other interpretations, it is the
      hallmark of systems that secure shape stability mainly through the prestress.
      Regardless of mechanism, these data establish a strong association between
      stiffness of HASM cells and the level of tensile stress within the cytoskeleton.

PMID- 11832349
TI  - Caffeine-stimulated GTH-II release involves Ca(2+) stores with novel properties.
AB  - Modulation of Ca(2+) stores with 10 mM caffeine stimulates robust secretion of
      gonadotropin (GTH-II) from goldfish gonadotropes. Although both endogenous forms
      of gonadotropin-releasing hormone (GnRH) utilize a common intracellular Ca(2+)
      store, sGnRH, but not cGnRH-II, uses an additional caffeine-sensitive mechanism.
      We examined caffeine signaling by using Ca(2+) imaging, electrophysiology, and
      cell-column perifusion. Although caffeine inhibited K+ channels, this action
      appeared to be unrelated to caffeine-induced GTH-II release, because the latter
      was insensitive to tetraethylammonium. The effects of caffeine also were not
      mediated by the cAMP/protein kinase A pathway. Instead, caffeine-evoked GTH-II
      responses were Ca(2+) signal dependent because they were abolished by 1,2-bis(2
      aminophenoxy)ethane-N,N,N',N'-tetraacetic acid loading. Caffeine generated
      localized Ca(2+) signals that began near secretory granules. Surprisingly,
      caffeine-stimulated GTH-II release was insensitive to 100 microM ryanodine and,
      unlike GnRH action, was unaffected by inhibitors of voltage-gated Ca(2+) channels
      or sarco(endo)plasmic reticulum Ca(2+)-ATPases. Collectively, these data indicate
      that caffeine-stimulated GTH-II release is not mediated by typical agonist
      sensitive Ca(2+) stores found in endoplasmic reticulum.

PMID- 11832348
TI  - Potentiation of nitric oxide-induced apoptosis in p53-/- vascular smooth muscle
      cells.
AB  - The functional role of p53 in nitric oxide (NO)-mediated vascular smooth muscle
      cell (VSMC) apoptosis remains unknown. In this study, VSMC from p53-/- and p53+/+
      murine aortas were exposed to exogenous or endogenous sources of NO.
      Unexpectedly, p53-/- VSMC were much more sensitive to the proapoptotic effects of
      NO than were p53+/+ VSMC. Furthermore, this paradox appeared to be specific to
      NO, because other proapoptotic agents did not demonstrate this differential
      effect on p53-/- cells. NO-induced apoptosis in p53-/- VSMC occurred
      independently of cGMP generation. However, mitogen-activated protein kinase
      (MAPK) pathways appeared to play a significant role. Treatment of the p53-/- VSMC
      with S-nitroso-N-acetylpenicillamine resulted in a marked activation of p38 MAPK
      and, to a lesser extent, of c-Jun NH(2)-terminal kinase, mitogen-activated
      protein kinase kinase (MEK) 1/2, and p42/44 (extracellular signal-regulated
      kinase, ERK). Furthermore, basal activity of the MEK-p42/44 (ERK) pathway was
      increased in the p53+/+ VSMC. Inhibition of p38 MAPK with SB-203580 or of MEK1/2
      with PD-98059 blocked NO-induced apoptosis. Therefore, p53 may protect VSMC
      against NO-mediated apoptosis, in part, through differential regulation of MAPK
      pathways.

PMID- 11832351
TI  - Loss of regulation of lipogenesis in the Zucker diabetic rat. II. Changes in
      stearate and oleate synthesis.
AB  - De novo lipogenesis and dietary fat uptake are two major sources of fatty acid
      deposits in fat of obese animals. To determine the relative contribution of fatty
      acids from these two sources in obesity, we have determined the distribution of
      c16 and c18 fatty acids of triglycerides in plasma, liver, and epididymal fat pad
      of Zucker diabetic fatty (ZDF) rats and their lean littermates (ZL) under two
      isocaloric dietary fat conditions. Lipogenesis was also determined using the
      deuterated water method. Conversion of palmitate to stearate and stearate to
      oleate was calculated from the deuterium incorporation by use of the tracer
      dilution principle. In the ZL rat, lipogenesis was suppressed from 70 to 24%,
      conversion of palmitate to stearate from 86 to 78%, and conversion of stearate to
      oleate from 56 to 7% in response to an increase in the dietary fat-to
      carbohydrate ratio. The results suggest that suppression of fatty acid synthase
      and stearoyl-CoA desaturase activities is a normal adaptive mechanism to a high
      fat diet. In contrast, de novo lipogenesis, chain elongation, and desaturation
      were not suppressed by dietary fat in the ZDF rat. The lack of ability to adapt
      to a high-fat diet resulted in a higher plasma triglyceride concentration and
      excessive fat accumulation from both diet and de novo synthesis in the ZDF rat.

PMID- 11832350
TI  - Defective Akt activation is associated with glucose- but not glucosamine-induced
      insulin resistance.
AB  - 3T3-L1 adipocytes develop insulin-resistant glucose transport upon preincubation
      with high glucose or glucosamine, provided insulin (0.6 nM) is present during
      preincubation. Insulin receptor substrate-1 (IRS-1)-associated
      phosphatidylinositol (PI) 3-kinase activity is unaffected (30). Total cellular
      IRS-1, PI 3-kinase, or Akt concentrations were unchanged. Akt activation in
      subcellular fractions was assessed by immunoblotting with two phospho-Akt
      specific antibodies. Upon acute 100 nM insulin stimulation, plasma membrane (PM)
      associated phospho-Akt was highest in cells preincubated in low glucose with no
      insulin, less in high glucose with no insulin, even less in low glucose+insulin,
      and lowest in high glucose+insulin. Only high glucose+insulin caused insulin
      resistant glucose transport. Acute insulin stimulation increased total PM-Akt
      about twofold after preincubation without insulin in low or high glucose.
      Preincubation with 0.6 nM insulin decreased Akt PM translocation by approximately
      25% in low and approximately 50% in high glucose. Preincubation with glucosamine
      did not affect Akt phosphorylation or translocation. CONCLUSIONS: chronic
      exposure to high glucose or insulin downregulates acute insulin-stimulated Akt
      activation, acting synergistically distal to PI 3-kinase. Maximal insulin
      activates more Akt than required for maximal glucose transport stimulation.
      Insulin resistance may ensue when PM-associated phospho-Akt decreases below a
      threshold. High glucose and glucosamine cause insulin resistance by different
      mechanisms in 3T3-L1 adipocytes.

PMID- 11832352
TI  - The calcium endocrine system of adolescent rhesus monkeys and controls before and
      after spaceflight.
AB  - The calcium endocrine system of nonhuman primates can be influenced by chairing
      for safety and the weightless environment of spaceflight. The serum of two rhesus
      monkeys flown on the Bion 11 mission was assayed pre- and postflight for vitamin
      D metabolites, parathyroid hormone, calcitonin, parameters of calcium
      homeostasis, cortisol, and indexes of renal function. Results were compared with
      the same measures from five monkeys before and after chairing for a flight
      simulation study. Concentrations of 1,25-dihydroxyvitamin D were 72% lower after
      the flight than before, and more than after chairing on the ground (57%, P <
      0.05). Decreases in parathyroid hormone did not reach significance. Calcitonin
      showed modest decreases postflight (P < 0.02). Overall, effects of spaceflight on
      the calcium endocrine system were similar to the effects of chairing on the
      ground, but were more pronounced. Reduced intestinal calcium absorption, losses
      in body weight, increases in cortisol, and higher postflight blood urea nitrogen
      were the changes in flight monkeys that distinguished them from the flight
      simulation study animals.

PMID- 11832353
TI  - Downregulated IRS-1 and PPARgamma in obese women with gestational diabetes:
      relationship to FFA during pregnancy.
AB  - Gestational diabetes mellitus (GDM) is associated with elevated postprandial free
      fatty acids (FFA) and insulin resistance; however, little is known about the
      cellular mechanisms underlying insulin resistance to suppress lipolysis during
      gestation. We evaluated the longitudinal changes in insulin suppression of FFA
      before pregnancy and in early (12-14 wk) and late (34-36 wk) gestation in obese
      subjects with normal glucose tolerance and in obese GDM subjects. Abdominal
      subcutaneous adipose tissue biopsies were also obtained during cesarean delivery
      from normal obese pregnant (Preg-Con), GDM, and nonpregnant obese control (Non
      Preg-Con) subjects during gynecological surgery. GDM subjects had higher basal
      plasma FFA before pregnancy (P = 0.055). Insulin's ability to suppress FFA levels
      declined from early to late gestation in both GDM and Preg-Con subjects and was
      significantly less in GDM subjects compared with Preg-Con subjects over time (P =
      0.025). Adipose tissue insulin receptor substrate (IRS)-1 protein levels were 43%
      lower (P = 0.02) and p85alpha subunit of phosphatidylinositol 3-kinase was
      twofold higher (P = 0.03) in GDM compared with Preg-Con subjects. The levels of
      peroxisome proliferator-activated receptor-gamma (PPARgamma) mRNA and protein
      were lower by 38% in Preg-Con (P = 0.006) and by 48% in GDM subjects (P = 0.005)
      compared with Non-Preg controls. Lipoprotein lipase and fatty acid-binding
      protein-2 mRNA levels were 73 and 52% lower in GDM compared with Preg-Con
      subjects (P < 0.002). Thus GDM women have decreased IRS-1, which may contribute
      to reduced insulin suppression of lipolysis with advancing gestation. Decreased
      PPARgamma and its target genes may be part of the molecular mechanism to
      accelerate fat catabolism to meet fetal nutrient demand in late gestation.

PMID- 11832354
TI  - The role of protein kinase C-delta in PTH stimulation of IGF-binding protein-5
      mRNA in UMR-106-01 cells.
AB  - We have investigated the role of protein kinase C (PKC) signal transduction
      pathways in parathyroid hormone (PTH) regulation of insulin-like growth factor
      binding protein-5 (IGFBP-5) gene expression in the rat osteoblast-like cell line
      UMR-106-01. Involvement of the PKC pathway was determined by the findings that
      bisindolylmaleimide I inhibited 40% of the PTH effect, and 1 microM bovine PTH-(3
      34) stimulated a 10-fold induction of IGFBP-5 mRNA. PTH-(1-34) and PTH-(3-34)
      (100 nM) both stimulated PKC-delta translocation from the membrane to the nuclear
      fraction. Rottlerin, a PKC-delta-specific inhibitor, and a dominant negative
      mutant of PKC-delta were both able to significantly inhibit PTH-(1-34) and PTH-(3
      34) induction of IGFBP-5 mRNA, suggesting a stimulatory role for PKC-delta in the
      effects of PTH. Phorbol 12-myristate 13-acetate (PMA) stimulated PKC-alpha
      translocation from the cytosol to the membrane and inhibited approximately 50% of
      the PTH-(1-34), forskolin, and 8-bromoadenosine 3',5'-cyclic monophosphate
      stimulated IGFBP-5 mRNA levels, suggesting that PKC-alpha negatively regulates
      protein kinase A (PKA)-mediated induction of IGFBP-5 mRNA. These results suggest
      that the induction of IGFBP-5 by PTH is both PKA and PKC dependent and PKC-delta
      is the primary mediator of the effects of PTH via the PKC pathway.

PMID- 11832355
TI  - Fetal hepatic and umbilical uptakes of glucogenic substrates during a glucagon
      somatostatin infusion.
AB  - To test the hypothesis that fetal hepatic glutamate output diverts the products
      of hepatic amino acid metabolism from hepatic gluconeogenesis, ovine fetal
      hepatic and umbilical uptakes of glucose and glucogenic substrates were measured
      before and during fetal glucagon-somatostatin (GS) infusion and during the
      combined infusion of GS, alanine, glutamine, and arginine. Before the infusions,
      hepatic uptake of lactate, alanine, glutamine, arginine, and other substrates was
      accompanied by hepatic output of pyruvate, aspartate, serine, glutamate, and
      ornithine. The GS infusion induced hepatic output of 1.00 +/- 0.07 mol glucose
      carbon/mol O(2) uptake, an equivalent reduction in hepatic output of pyruvate and
      glutamate carbon, a decrease in umbilical glucose uptake and placental uptake of
      fetal glutamate, an increase in hepatic alanine and arginine clearances, and a
      decrease in umbilical alanine, glutamine, and arginine uptakes. The latter result
      suggests that glucagon inhibits umbilical amino acid uptake. We conclude that
      fetal hepatic pyruvate and glutamate output is part of an adaptation to placental
      function that requires the fetal liver to maintain both a high rate of catabolism
      of glucogenic substrates and a low rate of gluconeogenesis.

PMID- 11832356
TI  - Effect of ibuprofen and acetaminophen on postexercise muscle protein synthesis.
AB  - We examined the effect of two commonly consumed over-the-counter analgesics,
      ibuprofen and acetaminophen, on muscle protein synthesis and soreness after high
      intensity eccentric resistance exercise. Twenty-four males (25 +/- 3 yr, 180 +/-
      6 cm, 81 +/- 6 kg, and 17 +/- 8% body fat) were assigned to one of three groups
      that received either the maximal over-the-counter dose of ibuprofen (IBU; 1,200
      mg/day), acetaminophen (ACET; 4,000 mg/day), or a placebo (PLA) after 10-14 sets
      of 10 eccentric repetitions at 120% of concentric one-repetition maximum with the
      knee extensors. Postexercise (24 h) skeletal muscle fractional synthesis rate
      (FSR) was increased 76 +/- 19% (P < 0.05) in PLA (0.058 +/- 0.012%/h) and was
      unchanged (P > 0.05) in IBU (35 +/- 21%; 0.021 +/- 0.014%/h) and ACET (22 +/-
      23%; 0.010 +/- 0.019%/h). Neither drug had any influence on whole body protein
      breakdown, as measured by rate of phenylalanine appearance, on serum creatine
      kinase, or on rating of perceived muscle soreness compared with PLA. These
      results suggest that over-the-counter doses of both ibuprofen and acetaminophen
      suppress the protein synthesis response in skeletal muscle after eccentric
      resistance exercise. Thus these two analgesics may work through a common
      mechanism to influence protein metabolism in skeletal muscle.

PMID- 11832357
TI  - Parathyroid gland volume increases with postmaturational aging in the rat.
AB  - To examine the pathophysiology of the age-related rise in the plasma
      concentration of parathyroid hormone (PTH), we studied the relationships among
      plasma immunoreactive PTH (iPTH), parathyroid gland volume, parathyroid cell
      proliferation rate, renal function, and blood Ca(2+) in male Fischer 344 rats
      aged 6-28 mo. Plasma iPTH increased 2.5-fold between 6 and 28 mo and correlated
      with parathyroid gland volume (r = 0.87). Gland volume began to increase as early
      as 6-12 mo of age and by 28 mo was threefold greater than at 6 mo. Gland
      expansion was a consequence of hyperplasia stimulated in part by an increase in
      cell proliferative activity late in life. Blood Ca(2+) and plasma inorganic
      phosphorus did not change significantly with age. Glomerular filtration rate
      decreased with age but only after the age of 24 mo. Unlike what has been observed
      in the human, these data suggest that the age-related increase in plasma iPTH in
      the rat is linked to parathyroid gland hyperplasia and that early gland growth
      does not appear to be associated with hypocalcemia or renal insufficiency, but
      rather to developmentally related metabolic changes. Later in life (>24 mo), the
      increase in parathyroid cell proliferation rate, further hyperplastic expansion
      of the gland, and increase in iPTH secretion appear to be associated with renal
      insufficiency.

PMID- 11832358
TI  - Minimal model S(I)=0 problem in NIDDM subjects: nonzero Bayesian estimates with
      credible confidence intervals.
AB  - The minimal model of glucose kinetics, in conjunction with an insulin-modified
      intravenous glucose tolerance test, is widely used to estimate insulin
      sensitivity (S(I)). Parameter estimation usually resorts to nonlinear least
      squares (NLS), which provides a point estimate, and its precision is expressed as
      a standard deviation. Applied to type 2 diabetic subjects, NLS implemented in
      MINMOD software often predicts S(I)=0 (the so-called "zero" S(I) problem),
      whereas general purpose modeling software systems, e.g., SAAM II, provide a very
      small S(I) but with a very large uncertainty, which produces unrealistic negative
      values in the confidence interval. To overcome these difficulties, in this
      article we resort to Bayesian parameter estimation implemented by a Markov chain
      Monte Carlo (MCMC) method. This approach provides in each individual the S(I) a
      posteriori probability density function, from which a point estimate and its
      confidence interval can be determined. Although NLS results are not acceptable in
      four out of the ten studied subjects, Bayes estimation implemented by MCMC is
      always able to determine a nonzero point estimate of S(I) together with a
      credible confidence interval. This Bayesian approach should prove useful in
      reanalyzing large databases of epidemiological studies.

PMID- 11832359
TI  - Weight loss-induced rise in plasma pollutant is associated with reduced skeletal
      muscle oxidative capacity.
AB  - In this study, we examined whether weight loss-induced changes in plasma
      organochlorine compounds (OC) were associated with those in skeletal muscle
      markers of glycolytic and oxidative metabolism. Vastus lateralis skeletal muscle
      enzyme activities and plasma OC (Aroclor 1260, polychlorinated biphenyl 153, p,p'
      DDE, beta-hexachlorocyclohexane, and hexachlorobenzene) were measured before and
      after a weight loss program in 17 men and 20 women. Both sexes showed a similar
      reduction in body weight (approximately 11 kg) in response to treatment, although
      men lost significantly more fat mass than women (P < 0.05). Enzymatic markers of
      glycolysis, phosphofructokinase (PFK) activity, and oxidative metabolism, beta
      hydroxyacyl-CoA dehydrogenase (HADH), citrate synthase (CS), and cytochrome c
      oxidase (COX) activities, remained unchanged after weight loss. A significant
      increase in plasma OC levels was observed in response to weight loss, an effect
      that was more pronounced in men. No relationship was observed between changes in
      OC and those in PFK activity in either sex [-0.31 < r < 0.12, not significant
      (NS)]. However, the greater the increase in plasma OC levels, the greater the
      reduction in oxidative enzyme (HADH, CS, COX) activities was in response to
      weight loss in men (-0.75 < r < -0.50, P < 0.05) but not in women (-0.33 < r <
      0.33, NS). These results suggest that the weight loss-induced increase in plasma
      pollutant levels is likely to be associated with reduced skeletal muscle
      oxidative metabolism in men but not in women.

PMID- 11832360
TI  - Oxytocin stimulation of RGS2 mRNA expression in cultured human myometrial cells.
AB  - Regulators of G protein signaling (RGS proteins) interact with Galpha(q) and
      Galpha(i) and accelerate GTPase activity. These proteins have been characterized
      only within the past few years, so our understanding of their importance is still
      preliminary. We examined the effect of oxytocin on RGS2 mRNA expression to help
      determine the role of RGS proteins in oxytocin signaling in human myometrial
      cells in primary culture. Oxytocin increased RGS2 mRNA concentration maximally by
      1 or 2 h in a dose-dependent and agonist-specific manner. RGS2 mRNA levels were
      also elevated by treatment with Ca(2+) ionophore, phorbol ester, or forskolin.
      Oxytocin's effects were completely inhibited by an intracellular Ca(2+) chelator
      and partially blocked by a protein kinase C inhibitor, indicating that
      intracellular Ca(2+) concentration is the primary signal for oxytocin elevation
      of RGS2 mRNA levels. Use of pharmacological inhibitors indicated that part of
      oxytocin-stimulated RGS2 mRNA expression is mediated by G(i)/tyrosine kinase
      activities. Although oxytocin does not stimulate increases in intracellular cAMP
      concentration, agents that elevate intracellular cAMP concentrations and cause
      myometrial relaxation may possibly cause heterologous desensitization to oxytocin
      via RGS2 expression. These results suggest that RGS2 may be important in
      regulating the myometrial response to oxytocin.

PMID- 11832361
TI  - Developmental decline in components of signal transduction pathways regulating
      protein synthesis in pig muscle.
AB  - Our previous studies showed that the feeding-induced stimulation of protein
      synthesis in skeletal muscle of neonatal pigs is accompanied by enhanced
      phosphorylation of the eukaryotic initiation factor (eIF)4E-binding protein (4E
      BP1) and the ribosomal protein S6 kinase (S6K1). These effects of feeding are
      substantially reduced with development. The goal of the present investigation was
      to delineate the basis for the reduced responsiveness to feeding observed in the
      older animals. In these studies, the content and activity of protein kinases
      located upstream of S6K1 and 4E-BP1 in signal transduction pathways activated by
      amino acids, insulin, and insulin-like growth factor I were examined in 7- and 26
      day-old pigs that were either fasted overnight or fed porcine milk after an
      overnight fast. Feeding stimulated phosphatidylinositol (PI) 3-kinase activity to
      the same extent in muscle of 7- and 26-day-old pigs, suggesting that PI 3-kinase
      is not limiting in muscle of older animals. In contrast, protein kinase B (PKB)
      activity was significantly less in muscle from 26- vs. 7-day-old pigs, regardless
      of nutritional status, suggesting that its activity is regulated by mechanisms
      distinct from PI 3-kinase. In part, the reduced PKB responsiveness can be
      attributed to a developmental decline in PKB content. Likewise, muscle content of
      the protein kinase termed mammalian target of rapamycin (mTOR) in 26-day-old pigs
      was <25% of that in 7-day-old animals. Finally, in agreement with our earlier
      work showing that S6K1 phosphorylation is reduced in older animals, S6K1 activity
      was stimulated to a lesser extent in 26- compared with 7-day-old pigs. Overall,
      the results suggest that the blunted protein synthetic response observed in 26-
      vs. 7-day-old neonatal pigs is due in part to decreased content and/or activity
      of signaling components downstream of PI 3-kinase, e.g., PKB, mTOR, and S6K1.

PMID- 11832362
TI  - Fatty acid oxidation and triacylglycerol hydrolysis are enhanced after chronic
      leptin treatment in rats.
AB  - Leptin acutely increases fatty acid (FA) oxidation and triacylglycerol (TG)
      hydrolysis and decreases TG esterification in oxidative rodent muscle. However,
      the effects of chronic leptin administration on FA metabolism in skeletal muscle
      have not been examined. We hypothesized that chronic leptin treatment would
      enhance TG hydrolysis as well as the capacity to oxidize FA in soleus (SOL)
      muscle. Female Sprague-Dawley rats were infused for 2 wk with leptin (LEPT; 0.5
      mg x kg(-1) x day(-1)) by use of subcutaneously implanted miniosmotic pumps.
      Control (AD-S) and pair-fed (PF-S) animals received saline-filled implants.
      Subsequently, FA metabolism was monitored for 45 min in isolated, resting, and
      contracting (20 tetani/min) SOL muscles by means of pulse-chase procedures. Food
      intake (-33 +/- 2%, P < 0.01) and body mass (-12.5 +/- 4%, P = 0.01) were reduced
      in both LEPT and PF-S animals. Leptin levels were elevated (+418 +/- 7%, P <
      0.001) in treated animals but reduced in PF-S animals (-73 +/- 8%, P < 0.05)
      relative to controls. At rest, TG hydrolysis was increased in leptin-treated rats
      (1.8 +/- 2.2, AD-S vs. 23.5 +/- 8.1 nmol/g wet wt, LEPT; P < 0.001). In
      contracting SOL muscles, TG hydrolysis (1.5 +/- 0.6, AD-S vs. 3.6 +/- 1.0
      micromol/g wet wt, LEPT; P = 0.02) and palmitate oxidation (18.3 +/- 6.7, AD-S
      vs. 45.7 +/- 9.9 nmol/g wet wt, LEPT; P < 0.05) were both significantly increased
      by leptin treatment. Chronic leptin treatment had no effect on TG esterification
      either at rest or during contraction. Markers of overall (citrate synthase) and
      FA (hydroxyacyl-CoA dehydrogenase) oxidative capacity were unchanged with leptin
      treatment. Protein expression of hormone-sensitive lipase (HSL) was also
      unaltered following leptin treatment. Thus leptin-induced increases in lipolysis
      are likely due to HSL activation (i.e., phosphorylation). Increased FA oxidation
      secondary to chronic leptin treatment is not due to an enhanced oxidative
      capacity and may be a result of enhanced flux into the mitochondrion (i.e.,
      carnitine palmitoyltransferase I regulation) or electron transport uncoupling
      (i.e., uncoupling protein-3 expression).

PMID- 11832363
TI  - Testosterone administration to older men improves muscle function: molecular and
      physiological mechanisms.
AB  - We investigated the effects of 6 mo of near-physiological testosterone
      administration to older men on skeletal muscle function and muscle protein
      metabolism. Twelve older men (> or =60 yr) with serum total testosterone
      concentrations <17 nmol/l (480 ng/dl) were randomly assigned in double-blind
      manner to receive either placebo (n = 5) or testosterone enanthate (TE; n = 7)
      injections. Weekly intramuscular injections were given for the 1st mo to
      establish increased blood testosterone concentrations at 1 mo and then changed to
      biweekly injections until the 6-mo time point. TE doses were adjusted to maintain
      nadir serum testosterone concentrations between 17 and 28 nmol/l. Lean body mass
      (LBM), muscle volume, prostate size, and urinary flow were measured at baseline
      and at 6 mo. Protein expression of androgen receptor (AR) and insulin-like growth
      factor I, along with muscle strength and muscle protein metabolism, were measured
      at baseline and at 1 and 6 mo of treatment. Hematological parameters were
      followed monthly throughout the study. Older men receiving testosterone increased
      total and leg LBM, muscle volume, and leg and arm muscle strength after 6 mo. LBM
      accretion resulted from an increase in muscle protein net balance, due to a
      decrease in muscle protein breakdown. TE treatment increased expression of AR
      protein at 1 mo, but expression returned to pre-TE treatment levels by 6 mo. IGF
      I protein expression increased at 1 mo and remained increased throughout TE
      administration. We conclude that physiological and near-physiological increases
      of testosterone in older men will increase muscle protein anabolism and muscle
      strength.

PMID- 11832364
TI  - Mutations in aldosterone synthase gene of Milan hypertensive rats: phenotypic
      consequences.
AB  - Using in vitro and in vivo methods, we have demonstrated increased sensitivity of
      adrenocortical steroidogenesis to ACTH in Milan hypertensive (MHS) compared with
      normotensive (MNS) rats and have investigated whether this is caused by mutations
      of steroidogenic enzymes. Genes encoding aldosterone synthase (CYP11B2) and
      11beta-hydroxylase (CYP11B1) in MHS and MNS have been cloned and sequenced.
      Nucleotide 752 (G) in exon 4 of MHS CYP11B2 differs from that of MNS (A); CYP11B1
      sequences were identical. The nucleotide 752 mutation caused a Q251R substitution
      in the amino acid sequence of MHS CYP11B2. The phenotype of MHS CYP11B2 alleles,
      when expressed in COS-1 cells, differed from that of MNS alleles. The relative
      activities of the three reactions catalyzed by CYP11B2 (11beta-hydroxylation of
      deoxycorticosterone, 18-hydroxylation of corticosterone, and dehydrogenation of
      18-hydroxycorticosterone) were estimated after incubation of transfected cells
      with [(14)C]deoxycorticosterone and analysis of radioactivity associated with
      deoxycorticosterone, corticosterone, 18 hydroxycorticosterone, and aldosterone.
      Both 11- and 18-hydroxylase activities were lower (19 and 12%, respectively; P <
      0.01 and P < 0.05) in cells transfected with MHS compared with MNS alleles,
      whereas 18-oxidase activity was 42% higher (P < 0.01). To assess the significance
      of the CYP11B2 mutation in vivo, DNA from F2 hybrid MHS x MNS rats was genotyped.
      MHS alleles were associated with lower urine volumes in both sexes, lower
      ventricle weights in male rats, but no difference in systolic or diastolic blood
      pressures between the sexes. We conclude that a mutation in CYP11B2 may affect
      aldosterone secretion in MHS; however, under normal environmental circumstances,
      we were unable to demonstrate any influence of this mutation on blood pressure.

PMID- 11832365
TI  - Glutamine and leucine nitrogen kinetics and their relation to urea nitrogen in
      newborn infants.
AB  - Glutamine kinetics and its relation to transamination of leucine and urea
      synthesis were quantified in 16 appropriate-for-gestational-age infants, four
      small-for-gestational-age infants, and seven infants of diabetic mothers.
      Kinetics were measured between 4 and 5 h after the last feed (fasting) and in
      response to formula feeding using [5-(15)N]glutamine, [1-(13)C,(15)N]leucine,
      [(2)H(5)]phenylalanine, and [(15)N(2)]urea tracers. Leucine nitrogen and
      glutamine kinetics during fasting were significantly higher than those reported
      in adults. De novo synthesis accounted for approximately 85% of glutamine
      turnover. In response to formula feeding, a significant increase (P = 0.04) in
      leucine nitrogen turnover was observed, whereas a significant decrease (P =
      0.002) in glutamine and urea rate of appearance was seen. The rate of appearance
      of leucine nitrogen was positively correlated (r(2) = 0.59, P = 0.001) with
      glutamine turnover. Glutamine flux was negatively correlated (r(2) = 0.39, P =
      0.02) with the rate of urea synthesis. These data suggest that, in the human
      newborn, glutamine turnover is related to a high anaplerotic flux into the
      tricarboxylic acid cycle as a consequence of a high rate of protein turnover. The
      negative relationship between glutamine turnover and the irreversible oxidation
      of protein (urea synthesis) suggests an important role of glutamine as a nitrogen
      source for other synthetic processes and accretion of body proteins.

PMID- 11832366
TI  - Lipid metabolism and resistin gene expression in insulin-resistant Fischer 344
      rats.
AB  - The interrelationship between insulin and leptin resistance in young Fischer 344
      (F344) rats was studied. Young F344 and Sprague-Dawley (SD) rats were fed regular
      chow. F344 animals had two- to threefold higher insulin and triglyceride
      concentrations and increased stores of triglycerides within liver and muscle.
      F344 animals gained more body fat. Both acyl-CoA oxidase (ACO) and carnitine
      palmitoyltransferase I gene expression were 20-50% less in F344 animals than in
      age-matched SD animals. Peroxisome proliferator-activated receptor-alpha gene
      expression was reduced in 70-day-old F344 animals. Finally, resistin gene
      expression was similar in 70-day-old SD and F344 animals. Resistin gene
      expression increased fivefold in F344 animals and twofold in SD animals from 70
      to 130 days, without a change in insulin sensitivity. We conclude that young F344
      animals have both insulin and leptin resistance, which may lead to diminished
      fatty oxidation and accumulation of triglycerides in insulin-sensitive target
      tissues. We did not detect a role for resistin in the etiology of insulin
      resistance in F344 animals.

PMID- 11832367
TI  - Myocellular triacylglycerol breakdown in females but not in males during
      exercise.
AB  - The resting content and use of myocellular triacylglycerol (MCTG) during 90 min
      of submaximal exercise [60% of peak oxygen uptake (VO(2 peak))] were studied in
      21 eumenorrheic female and 21 male subjects at different training levels
      [untrained (UT), moderately trained (MT), and endurance trained (END)]. Males and
      females were matched according to their VO(2 peak) expressed relative to lean
      body mass, physical activity level, and training history. All subjects ingested
      the same controlled diet for 8 days, and all females were tested in the
      midfollicular phase of the menstrual cycle. Resting MCTG, measured with the
      muscle biopsy technique, averaged 48.4 +/- 4.2, 48.5 +/- 8.4, and 52.2 +/- 5.8
      mmol/kg dry wt in UT, MT, and END females, respectively, and 34.1 +/- 4.9, 31.6
      +/- 3.3, and 38.4 +/- 3.0 mmol/kg dry wt in UT, MT, and END males, respectively
      (P < 0.001, females vs. males in all groups). Exercise decreased MCTG content in
      the female subjects by an average of 25%, regardless of training status, whereas
      in the male groups MCTG content was unaffected by exercise. The arterial plasma
      insulin concentration was higher (P < 0.05) and the arterial plasma epinephrine
      concentration was lower (P < 0.05) in the females than in the males at rest and
      during exercise. MCTG use was correlated to the resting concentration of MCTG (P
      < 0.001). We conclude that resting content and use of MCTG during exercise are
      related to gender and furthermore are independent of training status.

PMID- 11832368
TI  - Acute glucocorticoid treatment increases urinary biotin excretion and serum
      biotin.
AB  - Previous studies have demonstrated that glucocorticoids alter biotin metabolism.
      To extend these studies, the effect of dexamethasone on biotin pools was analyzed
      in rats consuming a purified diet containing a more physiological level of
      dietary biotin intake (0.06 mg/kg). Acute (5 h) dexamethasone administration (0.5
      mg/kg) elicited elevated urinary glucose output as well as elevated urinary
      biotin excretion and serum biotin. Renal and hepatic free biotin was also
      significantly elevated by acute dexamethasone administration. Chow-fed rats
      treated with an acute administration of dexamethasone demonstrated significantly
      elevated urinary glucose excretion, urinary biotin excretion, and serum biotin,
      but no change in tissue associated biotin was detected. Chronic administration of
      dexamethasone (0.5 mg/kg ip) over 4 days significantly elevated urinary glucose
      excretion 42% but had no effect on urinary biotin excretion, serum biotin, or
      hepatic- or renal-associated free biotin. These results demonstrate the existence
      of potentially novel regulatory pathways for total biotin pools and the
      possibility that experimental models with high initial biotin status may mask
      potentially important regulatory mechanisms.

PMID- 11832369
TI  - COX-2 inhibition attenuates anorexia during systemic inflammation without
      impairing cytokine production.
AB  - Anorexia and weight loss are frequent complications of acute and chronic
      infections and result from induction of cytokines, prostaglandins, and other
      inflammatory mediators that are critical for pathogen elimination. Selective
      attenuation of the hypophagic response to infection and maintenance of the
      production of factors essential for infection control would be a useful addition
      to antimicrobial therapy in the treatment of human disease. Here, we evaluate the
      relative contribution of cyclooxygenase (COX)-1- and COX-2-derived prostaglandins
      to anorexia and weight loss precipitated by systemic immune activation by
      lipopolysaccharide (LPS). Using COX isoform-selective pharmacological inhibitors
      and gene knockout mice, we found that COX-2 inhibition during LPS-induced
      inflammation results in preserved food intake and maintenance of body weight,
      whereas COX-1 inhibition results in augmented and prolonged weight loss.
      Regulation of neuropeptide Y, corticotropin-releasing hormone, leptin, and
      interleukin-6 does not change as a function of COX-2 inhibition after LPS
      administration. Our data implicate COX-2 inhibition as a therapeutic target to
      maintain nutritional status while still allowing a normal cytokine response
      during infection.

PMID- 11832370
TI  - Abdominal adiposity and insulin resistance in obese men.
AB  - We examined the independent relationships among various visceral and abdominal
      subcutaneous adipose tissue (AT) depots, glucose tolerance, and insulin
      sensitivity in 89 obese men. Measurements included an oral glucose tolerance test
      (OGTT), glucose disposal by euglycemic clamp, and abdominal and nonabdominal
      (e.g., peripheral) AT by magnetic resonance imaging (MRI). OGTT glucose and
      glucose disposal rates were related (P < 0.05) to visceral AT (r = 0.50 and 
      0.41, respectively). These observations remained significant (P < 0.05) after
      control for nonabdominal and abdominal subcutaneous AT, and maximal O(2)
      consumption (VO(2 max)). Abdominal subcutaneous AT was not a significant
      correlate (P > 0.05) of any metabolic variable after control for nonabdominal and
      visceral AT and VO(2 max). Division of abdominal subcutaneous AT into deep and
      superficial depots and visceral AT into intra- and extraperitoneal AT depots did
      not alter the observed relationships. Further analysis matched two groups of men
      for abdominal subcutaneous AT but also for low and high visceral AT. Men with
      high visceral AT had higher OGTT glucose values and lower glucose disposal rates
      compared with those with low visceral AT values (P < 0.05). A similar analysis
      performed on two groups of men matched for visceral AT but also for high and low
      abdominal subcutaneous AT revealed no statistically different values for any
      metabolic variable (P > 0.10). In conclusion, visceral AT alone is a strong
      correlate of insulin resistance independent of nonabdominal and abdominal
      subcutaneous AT and cardiovascular fitness. Subdivision of visceral and abdominal
      subcutaneous AT by MRI did not provide additional insight into the relationship
      between abdominal obesity and metabolic risk in obese men.

PMID- 11832371
TI  - N-3 polyunsaturated fatty acids prevent the defect of insulin receptor signaling
      in muscle.
AB  - A high-fat diet containing polyunsaturated fatty acids (PUFA: n-3 or n-6) given
      for 4 wk to 5-wk-old male Wistar rats induced a clear hyperglycemia (10.4 +/-
      0.001 mmol/l for n-6 rats and 10.1 +/- 0.001 for n-3 rats) and hyperinsulinemia
      (6.6 +/- 0.8 ng/ml for n-6 rats and 6.4 +/- 1.3 for n-3 rats), signs of insulin
      resistance. In liver, both diets (n-3 and n-6) significantly reduced insulin
      receptor (IR) number, IR and IR substrate (IRS)-1 tyrosine phosphorylation, and
      phosphatidylinositol (PI) 3'-kinase activity. In contrast, in leg muscle, IR
      density, as determined by Western blotting, was not affected, whereas IR and IRS
      1 tyrosine phosphorylation in response to insulin treatment was restored in
      animals fed with n-3 PUFA to normal; in n-6 PUFA, the phosphorylation was
      depressed, as evidenced by Western blot analysis using specific antibodies. In
      addition, PI 3'-kinase activity and GLUT-4 content in muscle were maintained at
      normal levels in rats fed with n-3 PUFA compared with rats fed a normal diet. In
      rats fed with n-6 PUFA, both PI 3'-kinase activity and GLUT-4 content were
      reduced. Furthermore, in adipose tissue and using RT-PCR, we show that both n-3
      and n-6 PUFA led to slight or strong reductions in p85 expression, respectively,
      whereas GLUT-4 and leptin expression was depressed in n-6 rats. The expression
      was not affected in n-3 rats compared with control rats. In conclusion, a high
      fat diet enriched in n-3 fatty acids maintained IR, IRS-1 tyrosine
      phosphorylation, and PI 3'-kinase activity and total GLUT-44 content in muscle
      but not in liver. A high-fat diet (n-3) partially altered the expression of p85
      but not that of GLUT-4 and leptin mRNAs in adipose tissue.

PMID- 11832373
TI  - Double isotope tracer method for measuring fractional zinc absorption:
      theoretical analysis.
AB  - Several approaches for estimation of fractional zinc absorption (FZA) by
      calculating the ratio of oral to intravenous stable isotopic tracer
      concentrations (at an appropriate time) in urine or plasma after their
      simultaneous administration have been proposed in the last decade. These simple
      to-implement approaches, often referred to as the double isotopic tracer ratio
      (DITR) method, are more attractive than the classical "deconvolution" method and
      the more commonly used single-tracer methods based on fecal monitoring and
      indicator dilution, after oral or intravenous tracer administration,
      respectively. However, the domain of validity of DITR for measuring FZA has
      recently been questioned. In this paper, we provide a theoretical justification
      of the validity of four different "approximate" formulations of the DITR
      technique by demonstrating mathematically that their accuracy is a consequence of
      the particular properties of zinc kinetics.

PMID- 11832372
TI  - Retinoic acid is detected at relatively high levels in the CNS of adult rats.
AB  - Retinoic acid (RA) is essential for cellular growth and differentiation in
      developing and adult animals. The central nervous system (CNS) suffers
      developmental defects if embryonic levels of RA are too high or too low. The
      production and function of RA in adult brain are unclear. We report that RA is
      present throughout the brain and spinal cord of adult, vitamin A-deficient (VAD)
      rats treated with a physiological amount of all-trans-retinol. The
      hippocampus/cortex contained the highest proportion of RA in the brain (27.2 +/-
      2.9% of the organic phase radioactivity, and 23.5 +/- 0.8% of the organic phase
      radioactivity extracted from spinal cord was RA). RA comprises a higher
      proportion of the retinoid pool in the CNS compared with amounts reported in
      other target tissues (E Werner and HF DeLuca. Arch Biochem Biophys 393: 262-270,
      2001). However, RA is not preferentially transported from the blood to the brain.
      There were 2.90 +/- 0.20 fmol RA/g tissue transported to the brain of VAD rats
      treated with 2.00 nmol [20-(3)H]all-trans-retinoic acid, but higher amounts of RA
      were delivered to the liver, testis, and spleen. Because RA is not transported
      preferentially to brain, this tissue likely synthesizes RA more efficiently than
      other target tissues.

PMID- 11832374
TI  - Progressive increase in human skeletal muscle AMPKalpha2 activity and ACC
      phosphorylation during exercise.
AB  - The effect of prolonged moderate-intensity exercise on human skeletal muscle AMP
      activated protein kinase (AMPK)alpha1 and -alpha2 activity and acetyl-CoA
      carboxylase (ACCbeta) and neuronal nitric oxide synthase (nNOSmu) phosphorylation
      was investigated. Seven active healthy individuals cycled for 30 min at a
      workload requiring 62.8 +/- 1.3% of peak O(2) consumption (VO(2 peak)) with
      muscle biopsies obtained from the vastus lateralis at rest and at 5 and 30 min of
      exercise. AMPKalpha1 activity was not altered by exercise; however, AMPKalpha2
      activity was significantly (P < 0.05) elevated after 5 min (approximately 2
      fold), and further elevated (P < 0.05) after 30 min (approximately 3-fold) of
      exercise. ACCbeta phosphorylation was increased (P < 0.05) after 5 min
      (approximately 18-fold compared with rest) and increased (P < 0.05) further after
      30 min of exercise (approximately 36-fold compared with rest). Increases in
      AMPKalpha2 activity were significantly correlated with both increases in ACCbeta
      phosphorylation and reductions in muscle glycogen content. Fat oxidation tended
      (P = 0.058) to increase progressively during exercise. Muscle creatine phosphate
      was lower (P < 0.05), and muscle creatine, calculated free AMP, and free AMP-to
      ATP ratio were higher (P < 0.05) at both 5 and 30 min of exercise compared with
      those at rest. At 30 min of exercise, the values of these metabolites were not
      significantly different from those at 5 min of exercise. Phosphorylation of
      nNOSmu was variable, and despite the mean doubling with exercise, statistically
      significance was not achieved (P = 0.304). Western blots indicated that
      AMPKapproximately 2 was associated with both nNOSmu and ACCbeta consistent with
      them both being substrates of AMPKalpha2 in vivo. In conclusion, AMPKalpha2
      activity and ACCbeta phosphorylation increase progressively during moderate
      exercise at approximately 60% of VO(2 peak) in humans, with these responses more
      closely coupled to muscle glycogen content than muscle AMP/ATP ratio.

PMID- 11832375
TI  - Human insulin release processes measured by intraportal sampling.
AB  - Insulin is secreted as a series of punctuated secretory bursts superimposed on
      variable basal insulin release. The contribution of these secretory bursts to
      overall insulin secretion has been estimated on the basis of peripheral vein
      sampling in humans to encompass > or =75% of overall insulin release. A similar
      contribution of the pulsatile mode of release was inferred in a canine model by
      use of portal vein sampling. The primary regulation of insulin secretion is
      through perturbation of the mass and frequency of these secretory bursts. The
      mode of delivery of insulin into the circulation seems important for insulin
      action; therefore, physiological conditions that alter the pattern of insulin
      release may affect insulin action through this mechanism. Transhepatic
      intraportal shunt in humans may provide access to portal vein samples, thus
      potentially improving the sensitivity of detecting and quantitating the
      frequency, mass, and amplitude of secretory bursts along with basal release and
      the regularity of these variables. To establish the insulin-secretory mechanism
      in nondiabetic humans by the use of portal vein sampling, we here assessed the
      mass, frequency, amplitude, and overall contribution of pulsatile insulin
      secretion by deconvolution analysis of portal vein insulin profiles. We find
      that, in nondiabetic humans fasted overnight, the portal vein insulin
      concentration oscillates at a periodicity of 4.1 +/- 0.2 min/pulse and with
      secretory peak amplitudes averaging 660% of basal (interpulse) release. The
      frequency was confirmed by spectral and autocorrelation analyses. The punctuated
      insulin-secretory bursts partially overlap and are responsible for the majority
      (70 +/- 4%) of insulin release. After ingestion of a mixed meal, the insulin
      release was increased through amplification of the secretory burst mass (507 +/-
      104 vs. 1,343 +/- 211 pmol x l(-1) x min(-1), P < 0.001), whereas frequency (4.4
      +/- 0.2 vs. 4.3 +/- 0.2, P = 0.86) and basal secretion (62 +/- 14 vs. 91 +/- 22
      pmol x l(-1) x min(-1), P = 0.33) were unaffected. One subject with diabetes and
      cirrhosis had a similar insulin-secretory pattern, whereas a subject with insulin
      dependent diabetes mellitus and minimal insulin release had preserved pulsatile
      release. A single subject was entrained to show agreement between entrained
      frequency and portal vein insulin oscillations. We conclude that insulin release
      in the human portal vein occurs at a mean periodicity of 4.4 +/- 0.2 min with a
      high signal-to-noise ratio (pulse amplitude 660% of basal). The impact of noise
      on the detected high frequency cannot be excluded.

PMID- 11832376
TI  - Diet-induced obesity and hepatic gene expression alterations in C57BL/6J and ICAM
      1-deficient mice.
AB  - The effects of high-fat feeding on the development of obesity were evaluated in
      intercellular adhesion molecule-1 (ICAM-1) knockout and C57BL/6J (B6) male mice
      fed a high-fat diet for < or =50 days. Serum and tissues were collected at
      baseline and after 1, 11, and 50 days on the diet. After 11 days on the diet,
      ICAM-1-deficient, but not B6, mice developed fatty livers and showed a
      significant increase in inguinal fat pad weight. At day 50, ICAM-1-deficient mice
      weighed less, and their adiposity index and circulating leptin levels were
      significantly lower than those of B6 controls. To better understand the early
      differential response to the diet, liver gene expression was analyzed at three
      time points by use of Affymetrix GeneChips. In both strains, a similar pattern of
      gene expression was detected in response to the high-fat diet. However, sterol
      regulatory element-binding protein-1, apolipoprotein A4, and adipsin mRNAs were
      significantly induced in ICAM-1-deficient livers, suggesting that these genes and
      their associated pathways may be involved in the acute diet response observed in
      the knockout mice.

PMID- 11832377
TI  - Vascular recruitment in skeletal muscle during exercise and hyperinsulinemia
      assessed by contrast ultrasound.
AB  - The purpose of this study was to noninvasively quantify the effects of insulin on
      capillary blood volume (capBV) and RBC velocity (V(RBC)) in skeletal muscle in
      vivo with the use of contrast-enhanced ultrasound. We performed contrast
      ultrasound of the rat hindlimb adductor muscles at baseline and after 2-h
      infusions of either insulin (3 or 40 mU x kg(-1) x min(-1)) or saline. Saline
      treated animals were also studied during contractile exercise. V(RBC) and capBV
      were calculated from the relation between pulsing interval and video intensity.
      Femoral artery blood flow, measured by a flow probe, increased with both
      contractile exercise and insulin. Contractile exercise increased capBV more than
      twofold and V(RBC) fivefold. Insulin also increased capBV more than twofold in a
      dose-dependent fashion but did not significantly alter V(RBC). Saline infusion
      did not significantly alter capBV, V(RBC), or femoral artery blood flow. We
      conclude that physiological changes in skeletal muscle capillary perfusion can be
      assessed in vivo with the use of contrast-enhanced ultrasound. Exercise increases
      both V(RBC) and capBV, whereas hyperinsulinemia selectively increases only capBV,
      which may enhance skeletal muscle glucose uptake.

PMID- 11832378
TI  - Calcitropic gene expression suggests a role for the intraplacental yolk sac in
      maternal-fetal calcium exchange.
AB  - The expression of calcitropic genes and proteins was localized within murine
      placenta during late gestation (the time frame of active calcium transfer) with
      an analysis of several gene-deletion mouse models by immunohistochemistry and in
      situ hybridization. Parathyroid hormone-related protein (PTHrP), the PTH/PTHrP
      receptor, calcium receptor, calbindin-D(9k), Ca(2+)-ATPase, and vitamin D
      receptor were all highly expressed in a localized structure of the murine
      placenta, the intraplacental yolk sac, compared with trophoblasts. In the PTHrP
      gene-deleted or Pthrp-null placenta in which placental calcium transfer is
      decreased, calbindin-D(9k) expression was downregulated in the intraplacental
      yolk sac but not in the trophoblasts. These observations indicated that the
      intraplacental yolk sac contains calcium transfer and calcium-sensing capability
      and that it is a probable route of maternal-fetal calcium exchange in the mouse.

PMID- 11832379
TI  - Identification of a novel glucose transporter-like protein-GLUT-12.
AB  - Facilitative glucose transporters exhibit variable hexose affinity and tissue
      specific expression. These characteristics contribute to specialized metabolic
      properties of cells. Here we describe the characterization of a novel glucose
      transporter-like molecule, GLUT-12. GLUT-12 was identified in MCF-7 breast cancer
      cells by homology to the insulin-regulatable glucose transporter GLUT-4. The GLUT
      12 cDNA encodes 617 amino acids, which possess features essential for sugar
      transport. Di-leucine motifs are present in NH(2) and COOH termini at positions
      similar to the GLUT-4 FQQI and LL targeting motifs. GLUT-12 exhibits 29% amino
      acid identity with GLUT-4 and 40% to the recently described GLUT-10. Like GLUT
      10, a large extracellular domain is predicted between transmembrane domains 9 and
      10. Genomic organization of GLUT-12 is highly conserved with GLUT-10 but distinct
      from GLUTs 1-5. Immunofluorescence showed that, in the absence of insulin, GLUT
      12 is localized to the perinuclear region in MCF-7 cells. Immunoblotting
      demonstrated GLUT-12 expression in skeletal muscle, adipose tissue, and small
      intestine. Thus GLUT-12 is potentially part of a second insulin-responsive
      glucose transport system.

PMID- 11832380
TI  - Neuropeptide Y.

PMID- 11832381
TI  - Physiological functions of the regulatory potassium channel subunit KCNE1.

PMID- 11832382
TI  - The multifaceted phenotype of the knockout mouse for the KCNE1 potassium channel
      gene.
AB  - Mutations of the KCNE1 gene (IsK, minK) are related to hereditary forms of
      cardiac arrhythmias, so-called long QT syndromes (LQT). Here we review the
      phenotype of a mouse model for the recessive form of LQT known as Jervell and
      Lange-Nielsen syndrome. KCNE1 knockout mice exhibit an enhanced QT-RR
      adaptability, which is probably part of the pathophysiological mechanism leading
      to life-threatening tachyarrhythmia in patients. Like patients, knockout mice are
      deaf and show vestibular symptoms due to an impaired endolymph production.
      Knockout mice show urinary and fecal salt wasting and volume depletion. The renal
      phenotype is due to diminished reabsorption of Na(+) and glucose. The mice are
      hypokalemic and have increased aldosterone levels. Besides volume depletion,
      aldosterone is elevated via a set-point shift for sensing of extracellular K(+)
      in aldosterone-secreting glomerulosa cells, which physiologically express KCNE1.
      In conclusion, KCNE1 knockout leads to a complex phenotype resulting from direct
      loss of KCNE1 and compensatory mechanisms. Murine KCNE1 physiology could be
      helpful for the pathophysiological understanding and perhaps gene-specific
      treatment of long QT patients.

PMID- 11832383
TI  - Sinoaortic denervation abolishes pressure resetting for daily physical activity
      in rabbits.
AB  - It has been speculated that if baroafferent signals are only related to the
      negative feedback control of arterial pressure (AP), then physical activity would
      increase the range of AP fluctuation in baroafferent-denervated animals. Mean AP
      (MAP), heart rate (HR), and cardiac output (CO) were measured for 24 h in free
      moving conscious rabbits. On the basis of hydrostatic pressure and
      electromyogram, MAP data taken during periods of physical activity and rest were
      selected from the overall 24-h MAP data and then converted into histograms.
      During physical activity, the mode of MAP histogram increased in intact rabbits
      and was unchanged in sinoaortic-denervated (SAD) rabbits. Movement increased the
      mode of total peripheral resistance (TPR) but did not significantly change CO in
      intact rabbits. Conversely in SAD rabbits, movement slightly decreased TPR and
      slightly increased CO. These findings indicate that arterial baroafferent signals
      are required to shift MAP to a higher pressure level by an increase in TPR but
      not in CO during a moving phase. These results suggest that baroafferent signals
      may not only minimize the fluctuating range of MAP through negative feedback
      control but also be involved in actively resetting MAP toward a higher pressure
      level during daily physical activity.

PMID- 11832384
TI  - Isolation and characterization of mitochondria-rich cell types from the gill of
      freshwater rainbow trout.
AB  - A magnetic cell separation technique (MACS) was developed for isolating and
      characterizing peanut lectin agglutinin positive (PNA(+)) cells from rainbow
      trout gills. Percoll density separated mitochondria-rich (MR) cells were serially
      labeled with PNA-FITC and an anti-FITC antibody covalently coupled to a 50-nm
      iron particle and then applied to a magnetic column. PNA(+) MR cells were
      enriched to >95% purity. Transmission electron microscopy analysis of both the
      PNA(+) and PNA negative (PNA(-)) fraction showed that PNA binds to MR chloride
      cells while the PNA(-) cell fraction is comprised of MR cells with features
      characteristic of pavement cells. Western blotting demonstrated that both PNA(+)
      and PNA(-) fractions had high levels of Na(+)-K(+)-ATPase and Sco1 expression;
      however, relative expression of H(+)-ATPase in PNA(+) and PNA(-) cells
      demonstrated that untreated fish had twofold higher H(+)-ATPase levels in PNA(-)
      cells relative to the PNA(+) cells. Furthermore, hypercapnic acidosis
      significantly increased the relative H(+)-ATPase expression on PNA(-) cells only,
      whereas metabolic alkalosis had no significant effect.

PMID- 11832385
TI  - Heat shock response reduces intestinal permeability in septic mice: potential
      role of interleukin-10.
AB  - Sepsis and other critical illnesses are associated with increased permeability of
      the intestinal mucosa. Loss of mucosal integrity may lead to multiple organ
      failure in these conditions. We tested the hypothesis that induction of the heat
      shock response reduces sepsis-induced increase in intestinal permeability. The
      heat shock response was induced in mice by intraperitoneal injection of 10 mg/kg
      sodium arsenite. Two hours later, at which time mucosal heat shock protein 72
      levels were increased, sepsis was induced by cecal ligation and puncture (CLP) or
      sham operation was performed. Sixteen hours after sham operation or CLP,
      intestinal permeability was determined by measuring the appearance in blood of
      4.4-kDa fluorescein isothiocyanate-conjugated dextran and 40-kDa horseradish
      peroxidase administered by gavage. Sepsis resulted in increased mucosal
      permeability for both markers, and this effect of sepsis was substantially
      reduced in mice treated with sodium arsenite. Plasma levels of the anti
      inflammatory cytokine interleukin (IL)-10 were increased in septic mice
      pretreated with sodium arsenite, and the protective effect of sodium arsenite on
      intestinal permeability in septic mice was reversed by treatment with anti-IL-10
      antibody. The present results suggest that sepsis-induced increase in mucosal
      permeability can be reduced by the heat shock response and that increased IL-10
      levels may be involved in the protective effects of the heat shock response.

PMID- 11832386
TI  - Total-body irradiation with high-LET particles: acute and chronic effects on the
      immune system.
AB  - Although the immune system is highly susceptible to radiation-induced damage,
      consequences of high linear energy transfer (LET) radiation remain unclear. This
      study evaluated the effects of 0.1 gray (Gy), 0.5 Gy, and 2.0 Gy iron ion
      (56Fe(26)) radiation on lymphoid cells and organs of C57BL/6 mice on days 4 and
      113 after whole body exposure; a group irradiated with 2.0 Gy silicon ions (28Si)
      was euthanized on day 113. On day 4 after 56Fe irradiation, dose-dependent
      decreases were noted in spleen and thymus masses and all major leukocyte
      populations in blood and spleen. The CD19(+) B lymphocytes were most
      radiosensitive and NK1.1(+) natural killer (NK) cells were most resistant. CD3(+)
      T cells were moderately radiosensitive and a greater loss of CD3(+)/CD8(+) T(C)
      cells than CD3(+)/CD4(+) T(H) cells was noted. Basal DNA synthesis was elevated
      on day 4, but response to mitogens and secretion of interleukin-2 and tumor
      necrosis factor-alpha were unaffected. Signs of anemia were noted. By day 113,
      high B cell numbers and low T(C) cell and monocyte percents were found in the 2.0
      Gy 56Fe group; the 2.0 Gy 2)Si mice had low NK cells, decreased basal DNA
      synthesis, and a somewhat increased response to two mitogens. Collectively, the
      data show that lymphoid cells and tissues are markedly affected by high linear
      energy transfer (LET) radiation at relatively low doses, that some aberrations
      persist long after exposure, and that different consequences may be induced by
      various densely ionizing particles. Thus simultaneous exposure to multiple
      radiation sources could lead to a broader spectrum of immune dysfunction than
      currently anticipated.

PMID- 11832387
TI  - Influence of vestibular activation on respiration in humans.
AB  - The purpose of this study was to determine the effects of the semicircular canals
      and otolith organs on respiration in humans. On the basis of animal studies, we
      hypothesized that vestibular activation would elicit a vestibulorespiratory
      reflex. To test this hypothesis, respiratory measures, arterial blood pressure,
      and heart rate were measured during engagement of semicircular canals and/or
      otolith organs. Dynamic upright pitch and roll (15 cycles/min), which activate
      the otolith organs and semicircular canals, increased respiratory rate (Delta2 +/
      1 and Delta3 +/- 1 breaths/min, respectively; P < 0.05). Dynamic yaw and lateral
      pitch (15 cycles/min), which activate the semicircular canals, increased
      respiration similarly (Delta3 +/- 1 and Delta2 +/- 1, respectively; P < 0.05).
      Dynamic chair rotation (15 cycles/min), which mimics dynamic yaw but eliminates
      neck muscle afferent, increased respiration (Delta3 +/- 1; P < 0.05) comparable
      to dynamic yaw (15 cycles/min). Increases in respiratory rate were graded as
      greater responses occurred during upright (Delta5 +/- 2 breaths/min) and lateral
      pitch (Delta4 +/- 1) and roll (Delta5 +/- 1) performed at 30 cycles/min.
      Increases in breathing frequency resulted in increases in minute ventilation
      during most interventions. Static head-down rotation, which activates otolith
      organs, did not alter respiratory rate (Delta1 +/- 1 breaths/min). Collectively,
      these data indicate that semicircular canals, but not otolith organs or neck
      muscle afferents, mediate increased ventilation in humans and support the concept
      that vestibular activation alters respiration in humans.

PMID- 11832388
TI  - Brain angiotensinergic mediation of enhanced water consumption in lactating rats.
AB  - The mechanism by which lactating rats increase fluid consumption to meet the
      demands of milk production is unknown. Because ANG II is the most potent
      dipsogenic stimulus known, this study examined whether angiotensinergic signaling
      plays a role in enhanced drinking in lactating rats. ANG II administered
      intracerebroventricularly caused a significantly greater dipsogenic response in
      lactating rats than in control rats, suggesting that dipsogenic responsivity to
      ANG II is enhanced in the brains of lactating rats. The angiotensin type 1 (AT1)
      ANG II receptor subtype antagonist SKF-108566, also given
      intracerebroventricularly, caused a significant reduction in water consumption in
      lactating rats, whereas it did not significantly affect water intake in control
      rats. In contrast, stimulation of drinking by the muscarinic agonist carbachol,
      also administered intracerebroventricularly, did not differ between lactating and
      control rats. Inhibition of drinking by the muscarinic antagonist atropine also
      did not differ significantly between lactating and control rats. These results
      suggest that the increased drinking in lactating rats involves an increased
      responsivity to ANG II in neurons that mediate dipsogenesis, as well as an
      enhancement in the amount of angiotensinergic input to these ANG II-responsive
      neurons.

PMID- 11832389
TI  - Effect of interleukin-18 on mouse core body temperature.
AB  - We have studied, using a telemetry system, the pyrogenic properties of
      recombinant murine interleukin-18 (rmIL-18) injected into the peritoneum of
      C57BL/6 mice. The effect of IL-18 was compared with the febrile response induced
      by human IL-1beta, lipopolysaccharide (LPS), and recombinant murine interferon
      gamma (rmIFN-gamma). Both IL-1beta and LPS induced a febrile response within the
      first hour after the intraperitoneal injection, whereas rmIL-18 (10-200
      microg/kg) and rmIFN-gamma (10-150 microg/kg) did not cause significant changes
      in the core body temperature of mice. Surprisingly, increasing doses of IL-18,
      injected intraperitoneally 30 min before IL-1beta, significantly reduced the IL
      1beta-induced fever response. In contrast, the same pretreatment with IL-18 did
      not modify the febrile response induced by LPS. IFN-gamma does not seem to play a
      role in the IL-18-mediated attenuation of IL-1beta-induced fever. In fact, there
      was no elevation of IFN-gamma in the serum of mice treated with IL-18, and a
      pretreatment with IFN-gamma did not modify the fever response induced by IL
      1beta. We conclude that IL-18 is not pyrogenic when injected intraperitoneally in
      C57BL/6 mice. Furthermore, a pretreatment with IL-18, 30 min before IL-1beta,
      attenuates the febrile response induced by IL-1beta.

PMID- 11832390
TI  - High-fat diet prevents eating response and attenuates liver ATP decline in rats
      given 2,5-anhydro-D-mannitol.
AB  - Administration of the fructose analog 2,5-anhydro-D-mannitol (2,5-AM) stimulates
      eating in rats fed a low-fat diet but not in those fed a high-fat diet that
      enhances fatty acid oxidation. The eating response to 2,5-AM treatment is
      apparently triggered by a decrease in liver ATP content. To assess whether
      feeding a high-fat diet prevents the eating response to 2,5-AM by attenuating the
      decrease in liver ATP, we examined the effects of the analog on food intake,
      liver ATP content, and hepatic phosphate metabolism [using in vivo 31P-NMR
      spectroscopy (NMRS)]. Injection (intraperitoneal) of 300 mg/kg 2,5-AM increased
      food intake in rats fed a high-carbohydrate/low-fat diet, but not in those fed
      high-fat/low-carbohydrate (HF/LC) food. Liver ATP content decreased in all rats
      given 2,5-AM compared with saline, but it decreased about half as much in rats
      fed the HF/LC diet. NMRS on livers of anesthetized rats indicated that feeding
      the HF/LC diet attenuates the effects of 2,5-AM on liver ATP by reducing
      phosphate trapping. These results suggest that rats consuming a high-fat diet do
      not increase food intake after injection of 2,5-AM, because the analog is not
      sufficiently phosphorylated and therefore fails to decrease liver energy status
      below a level that generates a signal to eat.

PMID- 11832391
TI  - Interactions of dietary fat and 2,5-anhydro-D-mannitol on energy metabolism in
      isolated rat hepatocytes.
AB  - The fructose analog 2,5-anhydro-D-mannitol (2,5-AM) stimulates feeding in rats by
      reducing ATP content in the liver. These behavioral and metabolic effects occur
      with rats fed a high-carbohydrate/low-fat (HC/LF) diet, but they are prevented or
      attenuated when the animals eat high-fat/low-carbohydrate (HF/LC) food. To
      examine the metabolic bases for this effect of diet, we assessed the actions of
      2,5-AM on ATP content, oxygen consumption, and substrate oxidation in isolated
      hepatocytes from rats fed one of the two diets. Compared with cells from rats fed
      the HC/LF diet ("HC/LF" cells), cells from rats fed the HF/LC diet ("HF/LC"
      cells) had similar ATP contents but lower oxygen consumption, decreased fructose,
      and increased palmitate oxidation. 2,5-AM did not decrease ATP content or oxygen
      consumption in HF/LC cells as much as it did in HC/LF hepatocytes, and it only
      affected fructose and palmitate oxidation in HC/LF cells. 31P-NMR spectroscopy
      indicated that differences in phosphate trapping accounted for differences in
      depletion of ATP by 2,5-AM. These results suggest that intake of the HF/LC diet
      prevents the eating response and attenuates the decline in liver ATP by shifting
      hepatocyte metabolism to favor fat over carbohydrate as an energy-yielding
      substrate.

PMID- 11832393
TI  - Molecular cloning and characterization of ryanodine receptor from unfertilized
      sea urchin eggs.
AB  - Unfertilized eggs of sea urchins (Hemicentrotus pulcherrimus) demonstrated cyclic
      ADP-ribose (cADPR)-induced Ca(2+) release and caffeine-induced Ca(2+) release,
      both of which were considered to be mediated through the ryanodine receptor
      (RyR). We cloned cDNAs for sea urchin egg RyR (suRyR), which encode a 597-kDa
      protein of 5,317 amino acids. suRyR shares common structural features with known
      RyRs: the well-conserved COOH-terminal domain, which forms a functional Ca(2+)
      channel, and a large hydrophilic NH2-terminal domain. suRyR shows amino acid
      sequence identity (43-45%) similar to the three mammalian RyR isoforms.
      Phylogenetic analysis indicates that suRyR branched from three isoforms of
      vertebrates before they diverged, suggesting that suRyR may be the only RyR
      isoform in the sea urchin. Four in-frame insertions were found in suRyR cDNAs,
      one of which was novel and unique, in that it had a cluster of serine residues.
      The transcripts with and without these insertions were found in the egg RNA.
      These results suggest that suRyR may be expressed as a functional Ca(2+)-induced
      Ca(2+) release channel, which might also be involved in cADPR-induced Ca(2+)
      release.

PMID- 11832392
TI  - Myocardial function in rat genetic models of low and high aerobic running
      capacity.
AB  - We recently evaluated treadmill aerobic running capacity in 11 inbred strains of
      rats and found that isolated working left ventricular function correlated (r =
      0.86) with aerobic running capacity. Among these 11 strains the Buffalo (BUF)
      hearts produced the lowest and the DA hearts the highest isolated cardiac output.
      The goal of this study was to investigate the components of cardiac function
      (i.e., coronary flow, heart rates, stroke volume, contractile dynamics, and cross
      bridge cycling) to characterize further the BUF and DA inbred strains as
      potential models of contrasting myocardial performance. Cardiac performance was
      assessed using the Langendorff-Neely working heart preparation. Isolated DA
      hearts were superior (P < 0.05) to the BUF hearts for cardiac output (63%),
      stroke volume (60%), aortic +dP/dt (47%), and aortic -dP/dt (46%). The mean
      alpha/beta-myosin heavy chain (MHC) isoform ratio for DA hearts was 21-fold
      higher relative to BUF hearts. At the steady-state mRNA level, DA hearts had a
      fivefold higher alpha/beta-ratio than the BUF hearts. The mean rate of ATP
      hydrolysis by MHCs was 64% greater in DA compared with BUF ventricles. These data
      demonstrate that the BUF and DA strains can serve as genetic models of
      contrasting low and high cardiac function.

PMID- 11832394
TI  - Regulation of SGLT1 expression in response to Na(+) intake.
AB  - In the chicken intestine, the reduction in Na(+) intake led to a decrease in the
      transport of alpha-methyl-D-glucoside in the ileum (reduction of 42%) and in the
      rectum (51%). These reductions were reversed within 24 h after resalination and
      were inversely correlated to the changes in aldosterone plasma concentration. The
      reduction in intestinal hexose transport in the low Na(+)-fed animals was due to
      a decrease in the number of Na(+)-dependent D-glucose cotransporters (SGLT1) in
      the rectum (46%) and in the ileum (38%). Northern blot analysis showed that
      specific SGLT1 mRNA was expressed in the jejunum, ileum, and rectum. The amount
      of SGLT1 mRNA was the same in all intestinal regions and was not affected by
      Na(+) intake, supporting the view that the effects of dietary Na(+) on intestinal
      hexose transport involve posttranscriptional regulation of SGLT1. This study
      suggests that changes in SGLT1 expression may be involved in the homeostasis of
      Na(+).

PMID- 11832395
TI  - Temperature dependence of gonadal regression in Syrian hamsters exposed to short
      day lengths.
AB  - We sought to determine whether ambient temperature (T(a)) affects gonadal
      function by altering the rate at which circadian rhythms entrain to short day
      lengths. Syrian hamsters were housed in cages where they received 14 h of light
      per day ("long days," 14L) at 22 degrees C. Hamsters were then transferred to
      cages to receive 10 h of light per day ("short days," 10L) and kept at 5, 22, or
      28 degrees C or were maintained in 14L at 22 degrees C. Body mass and estimated
      testis volume as well as duration of nocturnal locomotor activity (alpha),
      previously established as a reliable indicator of the duration of nocturnal
      melatonin secretion, were determined over the course of 24 wk. Testicular
      regression in short days was accelerated by 4 wk at 5 degrees C and delayed by 3
      wk at 28 degrees C relative to 22 degrees C. The interval between alpha-expansion
      and initiation of testicular regression was markedly affected by T(a) with delays
      of 0, 3, and 6 wk at 5, 22, and 28 degrees C, respectively. All hamsters held at
      5 and 22 degrees C underwent testicular regression, but 25% of those maintained
      at 28 degrees C failed to do so. We suggest that T(a) modulates testicular
      regression primarily by affecting responsiveness of neuroendocrine target tissues
      to long melatonin signals.

PMID- 11832396
TI  - Unequal autonegative feedback by GH models the sexual dimorphism in GH secretory
      dynamics.
AB  - Growth hormone (GH) secretion, controlled principally by a GH-releasing hormone
      (GHRH) and GH release-inhibiting hormone [somatostatin (SRIF)] displays vivid
      sexual dimorphism in many species. We hypothesized that relatively small
      differences within a dynamic core GH network driven by regulatory interactions
      among GH, GHRH, and SRIF explain the gender contrast. To investigate this notion,
      we implemented a minimal biomathematical model based on two coupled oscillators:
      time-delayed reciprocal interactions between GH and GHRH, which endow high
      frequency (40-60 min) GH oscillations, and time-lagged bidirectional GH-SRIF
      interactions, which mediate low-frequency (occurring every 3.3 h) GH volleys. We
      show that this basic formulation, sufficient to explain GH dynamics in the male
      rat [Farhy LS, Straume M, Johnson ML, Kovatchev BP, and Veldhuis JD. Am J Physiol
      Regulatory Integrative Comp Physiol 281: R38-R51, 2001], emulates the female
      pattern of GH release, if autofeedback of GH on SRIF is relaxed. Relief of GH
      stimulated SRIF release damps the slower volleylike oscillator, allowing
      emergence of the underlying high-frequency oscillations that are sustained by the
      GH-GHRH interactions. Concurrently, increasing variability of basal somatostatin
      outflow introduces quantifiable, sex-specific disorderliness of the release
      process typical of female GH dynamics. Accordingly, modulation of GH autofeedback
      on SRIF within the interactive GH-GHRH-SRIF ensemble and heightened basal SRIF
      variability are sufficient to transform the well-ordered, 3.3-h-interval,
      multiphasic, volleylike male GH pattern into a femalelike profile with irregular
      pulses of higher frequency.

PMID- 11832397
TI  - Dopaminergic metabolism in carotid bodies and high-altitude acclimatization in
      female rats.
AB  - We tested the hypothesis that ovarian steroids stimulate breathing through a
      dopaminergic mechanism in the carotid bodies. In ovariectomized female rats
      raised at sea level, domperidone, a peripheral D2-receptor antagonist, increased
      ventilation in normoxia (minute ventilation = +55%) and acute hypoxia (+32%).
      This effect disappeared after 10 daily injections of ovarian steroids
      (progesterone + estradiol). At high altitude (3,600 m, Bolivian Institute for
      High-Altitude Biology-IBBA, La Paz, Bolivia), neutered females had higher carotid
      body tyrosine hydroxylase activity (the rate-limiting enzyme for catecholamine
      synthesis: +129%) and dopamine utilization (+150%), lower minute ventilation (
      30%) and hypoxic ventilatory response (-57%), and higher hematocrit (+18%) and Hb
      concentration (+21%) than intact female rats. Consistent signs of arterial
      pulmonary hypertension (right ventricular hypertrophy) also appeared in
      ovariectomized females. None of these parameters was affected by gonadectomy in
      males. Our results show that ovarian steroids stimulate breathing by lowering a
      peripheral dopaminergic inhibitory drive. This process may partially explain the
      deacclimatization of postmenopausal women at high altitude.

PMID- 11832398
TI  - Regulation of MRP2-mediated transport in shark rectal salt gland tubules.
AB  - We examined endothelin-1 (ET-1) regulation of the xenobiotic efflux pump,
      multidrug resistance-associated protein isoform 2 (MRP2), in intact dogfish shark
      rectal salt gland tubules using a fluorescent substrate sulforhodamine 101 and
      confocal microscopy. Subnanomolar to nanomolar concentrations of ET-1 rapidly
      reduced the cell-to-lumen transport of sulforhodamine 101. These effects were
      prevented by an ET(B) receptor antagonist but not by an ET(A) receptor
      antagonist. Immunostaining with an antibody to mammalian ET(B) receptors showed
      specific localization to the basolateral membrane of the shark rectal gland
      epithelial cells. ET-1 effects on transport were blocked by a protein kinase C
      (PKC)-selective inhibitor, implicating PKC in ET-1 signaling. A protein kinase A
      (PKA)-selective inhibitor had no effect. Forskolin reduced luminal accumulation
      of sulforhodamine 101, but inhibition of PKA did not block the forskolin effect.
      Consistent with this observation, a cAMP analog that does not activate PKA
      reduced luminal accumulation of sulforhodamine 101. These results indicate that
      shark rectal gland transport on MRP2 is regulated by ET acting through an ET(B)
      receptor and PKC. In addition, cAMP affects transporter function through a PKA
      independent mechanism, possibly by competition for transport.

PMID- 11832399
TI  - Mating behavior is controlled by acute changes in metabolic fuels.
AB  - Mild food restriction for 48 h inhibits mating behavior in female musk shrews
      (Suncus murinus). However, mating behavior is restored after a 90-min feeding
      bout. In this series of experiments, we examined the role of metabolic fuels in
      this behavioral restoration. First, drugs reported to block glycolysis or fatty
      acid oxidation were given 2 h before mating. Both treatments inhibited mating in
      food-restricted females that were refed after treatment. Blood glucose levels
      were assessed in females that were fed ad libitum, food restricted, or food
      restricted and refed for 90 min. Food restriction significantly lowered blood
      glucose compared with ad libitum feeding or food restriction in combination with
      90 min of refeeding. However, neither glucose nor fat alone could substitute for
      food and promote mating behavior in food-restricted females. In addition,
      analysis of ketone bodies and body composition in females demonstrated low or
      undetectable levels of these energy substrates. Our data suggest that musk shrews
      have relatively little stored energy. Therefore, female musk shrews rely on
      continuous food intake and monitor multiple cues acutely, including glucose
      availability and fatty acid oxidation. This ensures that mating does not occur
      when adequate energy is unavailable.

PMID- 11832400
TI  - Manipulation of plasma uric acid in broiler chicks and its effect on leukocyte
      oxidative activity.
AB  - Birds have high metabolic rates, body temperatures, and plasma glucose
      concentrations yet physiologically age at a rate slower than comparably sized
      mammals. These studies were designed to test the hypothesis that the antioxidant
      uric acid protects birds against oxidative stress. Mixed sex broiler chicks (3 wk
      old) were fed diets supplemented or not with purines (0.6 mol hypoxanthine or
      inosine). Study 1 consisted of 18 female Cobb x Cobb broilers that were fed
      purines for 7 days, whereas study 2 consisted of 12 males in a 21-day trial.
      Study 3 involved 30 mixed sex broilers that were fed 40 or 50 mg allopurinol/kg
      body mass (BM) for 21 days, a drug that lowers plasma uric acid (PUA). PUA and
      leukocyte oxidative activity (LOA) were determined weekly for all studies. For
      study 2, pectoralis major shear force, relative kidney and liver sizes (RKS and
      RLS), and plasma glucose concentrations were also determined. In study 1, PUA
      concentration was increased three- and twofold (P < 0.001) in birds fed inosine
      or hypoxanthine, respectively, compared with control birds. LOA of birds
      supplemented with inosine was lower (P < 0.05) than that of control or
      hypoxanthine birds. In study 2, PUA concentrations were increased fivefold (P <
      0.001) in birds fed inosine and twofold (P < 0.001) in birds fed hypoxanthine
      compared with control birds at day 21. RKS (g/kg BM) was greater (P < 0.001) for
      chicks fed purine diets compared with control chicks. Muscle shear value was
      lower (P < 0.05) in chicks fed purine diets. PUA concentration was decreased (P <
      0.001) in birds consuming allopurinol diets, whereas LOA was increased (P < 0.01)
      in study 3. These studies show that PUA concentrations can be related to
      oxidative stress in birds, which can be linked to tissue aging.

PMID- 11832401
TI  - Melatonin in rat milk and the likelihood of its role in postnatal maternal
      entrainment of rhythms.
AB  - The rhythm of melatonin in rat milk and the capacity of pups to synthesize and
      metabolize melatonin were studied. Melatonin was undetectable in milk in the
      light (< 21 pM), but increased rapidly 2-4 h after dark to peak at 357 +/- 66 pM
      at mid-dark. Oral or subcutaneous administration of melatonin to 5- and 10-day
      old pups resulted in peak plasma melatonin levels 30 min after administration and
      rapid metabolism. Increases in pineal and plasma melatonin levels at night were
      detected at 5 and 6 days of age, respectively. Isoproterenol administration (2
      microg/g body wt) at mid-light to day 10 pups increased plasma melatonin from 312
      +/- 40 pM to 1,298 +/- 160 pM, whereas propranolol (2 microg/g body wt)
      suppressed nocturnal melatonin secretion from 1,270 +/- 128 pM to 395 +/- 66 pM.
      The rise of pineal and plasma melatonin in day 10 pups occurred 1 and 2 h after
      dark onset, respectively, preceding the onset in dams by 3 and 4 h, respectively.
      Propranolol administration to 2- and 5-day lactating dams inhibited plasma and
      milk melatonin at night but had no effect on their suckling pups. Transfer of
      melatonin via the milk is unlikely to provide an entraining signal for rat pups.

PMID- 11832402
TI  - Renal responses to plasma volume expansion and hyperosmolality in fasting seal
      pups.
AB  - Renal responses were quantified in northern elephant seal (Mirounga
      angustirostris) pups during their postweaning fast to examine their excretory
      capabilities. Pups were infused with either isotonic (0.9%; n = 8; Iso) or
      hypertonic (16.7%; n = 7; Hyper) saline via an indwelling catheter such that each
      pup received 3 mmol NaCl/kg. Diuresis after the infusions was similar in
      magnitude between the two treatments. Osmotic clearance increased by 37% in Iso
      and 252% in Hyper. Free water clearance was reduced 3.4-fold in Hyper but was not
      significantly altered in Iso. Glomerular filtration rate increased 71% in the 24
      h period after Hyper, but no net change occurred during the same time after Iso.
      Natriuresis increased 3.6-fold in Iso and 5.3-fold in Hyper. Iso decreased plasma
      arginine vasopressin (AVP) and cortisol acutely, whereas Hyper increased plasma
      and excreted AVP and cortisol. Iso was accompanied by the retention of water and
      electrolytes, whereas the Hyper load was excreted within 24 h. Natriuresis is
      attributed to increased filtration and is independent of an increase in atrial
      natriuretic peptide and decreases in ANG II and aldosterone. Fasting pups appear
      to have well-developed kidneys capable of both extreme conservation and excretion
      of Na(+).

PMID- 11832403
TI  - Suppression of vagal motor activities evokes laryngeal afferent-mediated
      inhibition of gastric motility.
AB  - We previously reported that the activation of water-responsive afferents in the
      superior laryngeal nerve was responsible for the inhibition of gastric motility.
      The present study was undertaken to clarify the roles of the vagal preganglionic
      neurons responsible for laryngeal afferent-mediated inhibition of gastric
      motility. Intravenous injection of atropine abolished the inhibition of motility
      in both the distal and the proximal stomach induced by water administration into
      the larynx. The neurons in the dorsal motor nucleus of the vagus (DMV), which
      project to the abdominal viscera, were exclusively inhibited by water
      administration. Taken together, inhibition of neurons in the DMV induces
      inhibition of gastric motility evoked by laryngeal water-responsive afferents via
      a cholinergic pathway. Because chemical lesions of the intermediate DMV, but not
      the caudal DMV, abolished the inhibition of the distal stomach motility induced
      by water administration, the intermediate DMV is responsible for the inhibition
      shown in the distal stomach.

PMID- 11832404
TI  - Glycogen phosphorylase and pyruvate dehydrogenase transformation in white muscle
      of trout during high-intensity exercise.
AB  - We examined the regulation of glycogen phosphorylase (Phos) and pyruvate
      dehydrogenase (PDH) in white muscle of rainbow trout during a continuous bout of
      high-intensity exercise that led to exhaustion in 52 s. The first 10 s of
      exercise were supported by creatine phosphate hydrolysis and glycolytic flux from
      an elevated glycogenolytic flux and yielded a total ATP turnover of 3.7 micromol
      x g wet tissue(-1) x s(-1). The high glycolytic flux was achieved by a large
      transformation of Phos into its active form. Exercise performed from 10 s to
      exhaustion was at a lower ATP turnover rate (0.5 to 1.2 micromol x g wet tissue(
      1) x s(-1)) and therefore at a lower power output. The lower ATP turnover was
      supported primarily by glycolysis and was reduced because of posttransformational
      inhibition of Phos by glucose 6-phosphate accumulation. During exercise, there
      was a gradual activation of PDH, which was fully transformed into its active form
      by 30 s of exercise. Oxidative phosphorylation, from PDH activation, only
      contributed 2% to the total ATP turnover, and there was no significant activation
      of lipid oxidation. The time course of PDH activation was closely associated with
      an increase in estimated mitochondrial redox (NAD(+)-to-NADH concentration
      ratio), suggesting that O2 was not limiting during high-intensity exercise. Thus
      anaerobiosis may not be responsible for lactate production in trout white muscle
      during high-intensity exercise.

PMID- 11832405
TI  - Serotonergic mechanisms of the lateral parabrachial nucleus and cholinergic
      induced sodium appetite.
AB  - Central cholinergic mechanisms are suggested to participate in osmoreceptor
      induced water intake. Therefore, central injections of the cholinergic agonist
      carbachol usually produce water intake (i.e., thirst) and are ineffective in
      inducing the intake of hypertonic saline solutions (i.e., the operational
      definition of sodium appetite). Recent studies have indicated that bilateral
      injections of the serotonin receptor antagonist methysergide into the lateral
      parabrachial nucleus (LPBN) markedly increases salt intake in models involving
      the activation of the renin-angiotensin system or mineralocorticoid hormones. The
      present studies investigated whether sodium appetite could be induced by central
      cholinergic activation with carbachol (an experimental condition where only water
      is typically ingested) after the blockade of LPBN serotonergic mechanisms with
      methysergide treatment in rats. When administered intracerebroventricularly in
      combination with injections of vehicle into both LPBN, carbachol (4 nmol) caused
      water drinking but insignificant intake of hypertonic saline. In contrast, after
      bilateral LPBN injections of methysergide (4 microg), intracerebroventricular
      carbachol induced the intake of 0.3 M NaCl. Water intake stimulated by
      intracerebroventricular carbachol was not changed by LPBN methysergide
      injections. The results indicate that central cholinergic activation can induce
      marked intake of hypertonic NaCl if the inhibitory serotonergic mechanisms of the
      LPBN are attenuated.

PMID- 11832406
TI  - Influence of baroreflex on volume elasticity of heart and aorta in the rabbit.
AB  - Optimal ventriculoaortic coupling includes tuning of elastic properties. The
      ratio of effective arterial elastance and left ventricular endsystolic elastance
      is often taken as a measure for mechanical and energetical efficiency. The
      present study determined the time course of ventricular and aortic volume
      elasticity (VE = dp/dV) throughout a complete heartbeat. This was achieved by
      using changes of eigenfrequency of two catheter-transducer systems under closed
      chest conditions in rabbits. Short-term VE modulation was studied by a baroreflex
      response, as induced by pressure changes applied to the carotid sinus. Long-term
      changes were studied in atherosclerotic rabbits (12 wk of high-cholesterol
      feeding). The time course and mean values of ventricular and aortic VE were
      changed by the baroreflex stimulus. Cholesterol feeding diminished the response.
      The degree of ventriculoaortic coupling, as quantified by VE(Aorta)/VE(Ventricle)
      ratio, varied during a single ejection period. The large span allows either
      maximal energetical efficiency or maximal stroke work. Although normal rabbits
      adjusted their ventriculoaortic coupling during baroreflex input, the cholesterol
      fed rabbits failed to do so.

PMID- 11832407
TI  - Role of spinal NMDA and non-NMDA receptors in the pressor reflex response to
      abdominal ischemia.
AB  - Abdominal ischemia induces a pressor reflex caused mainly by C-fiber afferent
      stimulation. Because excitatory amino acids, such as glutamate, bind to N-methyl
      D-aspartate (NMDA) and non-NMDA [dl-alpha-amino-3-hydroxy-5-methylisoxazole-4
      propionate (AMPA)] receptors and serve as important spinal neurotransmitters, we
      hypothesized that both receptors play a role in the abdominal ischemia pressor
      reflex. In chloralose-anesthetized cats, NMDA receptor blockade with 25.0 mM dl-2
      amino-5-phosphonopentanoate did not alter the pressor reflex (33 +/- 9 to 33 +/-
      7 mmHg, P > 0.05, n = 4), whereas AMPA receptor blockade with 4.0 mM 6-nitro-7
      sulfamylbenzo(f)quinoxaline-2,3-dione significantly attenuated the reflex (29 +/-
      5 to 16 +/- 4 mmHg, P < 0.05, n = 6). Because several studies suggest that
      anesthesia masks the effects of glutamatergic receptors, this experiment was
      repeated on decerebrate cats, and in this group, NMDA receptor blockade with 25.0
      mM dl-2-amino-5-phosphonopentanoate significantly altered the pressor reflex (36
      +/- 3 to 25 +/- 4 mmHg, P < 0.05, n = 5). Our combined data suggest that spinal
      NMDA and AMPA receptors play a role in the abdominal ischemia pressor reflex.

PMID- 11832408
TI  - Temporal increase in the reactivity of pulmonary vasculature to substance P in
      chronically hypoxic rats.
AB  - We previously demonstrated that the pulmonary vascular response to substance P
      (SP) increased in chronically hypoxic rats. This study explored the temporal
      increase in reactivity of the pulmonary vascular response to SP and its
      underlying mechanisms. First, young female Wistar rats were exposed to sea level
      (SL) or simulated high altitude (HA) for 15 h/day for 3 days, 1 wk, 2 wk, and 4
      wk. Lungs were isolated and perfused with 4% bovine serum albumin in Krebs
      Henseleit buffer solution. SP (1.5 x 10(-4) M) induced significant increases in
      pulmonary arterial pressure (P(pa)), venous pressure (P(v)), capillary pressure
      (P(c)), arterial resistance (R(a)), and filtration coefficient (K(fc)) in SL
      lungs. Increases in P(pa) and R(a) were significantly augmented in HA lungs, with
      a temporal increase trend peaking at 2 wk of HA exposure. The selective
      neurokinin (NK) type 1 (NK1) receptor antagonist SR-14033 significantly
      attenuated SP-induced increases in P(pa), P(v), P(c), R(a), and K(fc) in SL
      lungs. In lungs exposed to HA for 2 wk, SR-14033 suppressed the effect of SP on
      P(pa). Also, chronic hypoxia induced significant increases in NK1 receptors and
      NK1 receptor mRNA, with a temporal trend. We conclude that chronic hypoxia
      temporally augments SP-induced vascular responses, which are closely associated
      with increases in NK1 receptors and gene expression.

PMID- 11832409
TI  - Role of thromboxane receptors in the dipsogenic response to central angiotensin
      II.
AB  - Central angiotensin II (ANG II) regulates thirst. Because thromboxane A2
      prostaglandin H2 (TP) receptors are expressed in the brain and mediate some of
      the effects of ANG II in the vasculature, we investigated the hypothesis that TP
      receptors mediate the drinking response to intracerebroventricular (icv)
      injections of ANG II. Pretreatment with the specific TP-receptor antagonist
      ifetroban (Ifet) decreased water intake with 50 ng/kg icv ANG II (ANG II + Veh,
      7.2 +/- 0.7 ml vs. ANG II + Ifet, 2.8 +/- 0.8 ml; n = 5 rats; P < 0.001) but had
      no effect on water intake induced by hypertonic saline (NaCl + Veh, 8.4 +/- 1.1
      ml vs. NaCl + Ifet, 8.9 +/- 1.8 ml; n = 5 rats; P = not significant).
      Administration of 0.6 microg/kg icv of the TP-receptor agonist U-46,619 did not
      induce drinking when given alone but did increase the dipsogenic response to a
      near-threshold dose of 15 ng/kg icv ANG II (ANG II + Veh, 1.1 +/- 0.7 vs. ANG II
      + U-46,619, 4.5 +/- 0.9 ml; n = 5 rats; P < 0.01). We conclude that central TP
      receptors contribute to the dipsogenic response to ANG II.

PMID- 11832410
TI  - Activation of adenylyl cyclases, regulation of insulin status, and cell survival
      by G(alpha)olf in pancreatic beta-cells.
AB  - Because we recently identified the G(alpha)olf subunit in rat pancreatic beta
      cells, we investigated the downstream effectors and the biological functions of
      this G protein in HEK-293T cells and the insulin-secreting mouse betaTC-3 cell
      line. With the use of transient transfection of HEK-293T cells with
      constitutively activated G(alpha)olf (G(alpha)olfQ214L, i.e., AG(alpha)olf),
      together with expression vectors encoding the adenylyl cyclase (AC) isoforms (AC
      I to -VIII and soluble AC), compared with cotransfections using AG(alphas)
      (G(alphas)R201C), we observed that AG(alpha)olf preferentially activates AC-I and
      -VIII, which are also expressed in beta-cells. Stable overexpression of wild-type
      or AG(alpha)olf in betaTC-3 cells resulted in partial attenuation of insulin
      secretion and biosynthesis, suggesting that chronic activation of the G(alpha)olf
      signaling pathway is associated with beta-cell desensitization. In agreement,
      transfected betaTC-3 cells present a decreased insulin content with respect to
      parental cells, whereas the proinsulin convertases PC-1 and PC-2 were unaffected.
      Furthermore, betaTC-3-AG(alpha)olf cells are resistant to serum starvation
      induced apoptosis. Our findings suggest that G(alpha)olf is involved in insulin
      status, cell survival, and regeneration of the insulin-secreting beta-cells
      during development and diabetes.

PMID- 11832411
TI  - Endothelin-A receptors and NO mediate decrease in arterial pressure during
      recovery from restraint.
AB  - We investigated the role of central endothelin-A (ET(A)) receptors and nitric
      oxide (NO) in regulating arterial pressure during restraint stress and recovery
      from stress. Rats received intracerebroventricular (icv) injections of the ET(A)
      receptor antagonist BQ123 (24 microg/kg) and were then subjected to two restraint
      rest cycles (1 h of restraint and 1 h of rest/cycle). Although mean arterial
      pressure (MAP) values in BQ123-treated and control rats increased at the onset of
      restraint and remained elevated during restraint, MAP values in BQ123-treated
      rats were consistently greater than in control rats. During rest periods, MAP
      values in control rats decreased to below baseline levels, whereas those in BQ123
      treated rats remained significantly higher. NO content was decreased in the brain
      stems of BQ123-treated compared with control rats after the 4-h protocol.
      Injections (icv) of the NO synthase (NOS) inhibitor N(G)-nitro-L-arginine (L-NNA)
      eliminated the decreases in MAP values during rest periods in both BQ123-treated
      and control rats. Inhibition of neuronal NOS with icv injection of 7
      nitroindazole sodium salt resulted in MAP values intermediate between control
      rats and rats receiving L-NNA. These results support the hypothesis that
      endothelin acts through ET(A) receptors in the brain, possibly via release of NO,
      to decrease arterial pressure during restraint and recovery from restraint.

PMID- 11832412
TI  - High-resolution magnetic resonance imaging tracks changes in organ and tissue
      mass in obese and aging rats.
AB  - Magnetic resonance imaging (MRI) has the ability to discriminate between various
      soft tissues in vivo. Whole body, specific organ, total adipose tissue (TAT),
      intra-abdominal adipose tissue (IAAT), and skeletal muscle (SM) weights
      determined by MRI were compared with weights determined by dissection and
      chemical analysis in two studies with male Sprague-Dawley rats. A 4.2-T MRI
      machine acquired high-resolution, in vivo, longitudinal whole body images of rats
      as they developed obesity or aged. Weights of the whole body and specific tissues
      were determined using computer image analysis software, including semiautomatic
      segmentation algorithms for volume calculations. High correlations were found for
      body weight (r = 0.98), TAT (r = 0.99), and IAAT (r = 0.98) between MRI and
      dissection and chemical analyses. MRI estimated the weight of the brain, kidneys,
      and spleen with high accuracy (r > 0.9), but overestimated IAAT, SM, and liver
      volumes. No differences were detected in organ weights using MRI and dissection
      measurements. Longitudinal MRI measurements made during the development of
      obesity and aging accurately represented changes in organ and tissue mass.

PMID- 11832413
TI  - Functional restitution of cardiac control in heart transplant patients.
AB  - Cardiovascular control is fundamentally altered after heart transplantation (HT)
      because of surgical denervation of the heart. The main goal of this work was the
      noninvasive characterization of cardiac rate control mechanisms after HT and the
      understanding of their nature. We obtained 25 recordings from 13 male HT patients
      [age = 28-68 yr, time after transplant (TAT) = 0.5-62.5 mo]. The control group
      included 14 healthy men (age = 28-59 yr). Electrocardiogram, continuous blood
      pressure (BP), and respiration were recorded for 45 min in the supine position
      and then during active change of posture (CP) to standing. The signals were
      analyzed in the time domain [mean and variance of heart rate (HR) and rise time
      of HR in response to CP] and the frequency domain [low and high frequency (LF and
      HF)]. Our principal finding was the consistent pattern of evolution of the HR
      response to standing: from no response, via a slow response (>40 s, TAT > 6 wk),
      to a fast increase (<20 s, TAT > 24 mo). HR response correlated with TAT (P <
      0.001). LF correlated with HR response to CP (P < 0.0001); HF and HR did not. An
      important finding was the presence of very-high-frequency peaks in the power
      spectrum of HR and BP fluctuations. Extensive arrhythmias tended to appear at the
      TAT that corresponds to the transition from slow to fast HR response to CP. Our
      results indicate a biphasic evolution in cardiac control mechanisms from lack of
      control to a first-order control loop followed by partial sympathetic
      reinnervation and, finally, the direct effect of the old sinoatrial node on the
      pacemaker cell of the new sinoatrial node. There was no indication of vagal
      reinnervation.

PMID- 11832414
TI  - The influence of aging on the human sympathetic nervous system and brain
      norepinephrine turnover.
AB  - Investigating aging effects on the sympathetic nervous system and ascertaining
      underlying central nervous system (CNS) mechanisms mediating sympathetic
      stimulation is clinically pertinent because of the possible interconnection of
      cardiovascular disease development with age-dependent sympathetic nervous
      changes. Because of previous evidence linking human CNS neuronal noradrenergic
      function and sympathetic activity, we investigated the influence of aging on
      brain norepinephrine turnover in 22 healthy men aged 20-30 yr and 16 healthy men
      aged 60-75 yr by measuring the internal jugular venous overflow of norepinephrine
      and its lipophilic metabolites. Sympathoneural and adrenal medullary function was
      also studied, using plasma catecholamine isotope dilution methodology and
      regional central venous sampling. In the older men there was increased
      norepinephrine turnover in suprabulbar subcortical brain regions, 317 +/- 50
      ng/min compared with 107 +/- 18 ng/min in younger men. A differentiated
      sympathetic nervous activation was also present in older men. Overall, levels of
      both cardiac and hepatomesenteric norepinephrine spillover were directly
      correlated with subcortical norepinephrine turnover. These findings suggest that
      in sympathetic nervous activation accompanying aging, as has previously been
      demonstrated with the sympathetic nervous stimulation in human hypertension and
      heart failure, there is an underlying sympathoexcitatory influence of
      noradrenergic projections to suprabulbar subcortical regions.

PMID- 11832415
TI  - Vascular reactivity in intrapulmonary arteries of chicken embryos during
      transition to ex ovo life.
AB  - The present study aimed to characterize pulmonary vascular reactivity in the
      chicken embryo from the last stage of prenatal development and throughout the
      perinatal period. Isolated intrapulmonary arteries from non-internally pipped
      embryos at 19 days of incubation and from internally and externally pipped
      embryos at 21 days of incubation were studied. Arterial diameter and contractile
      responses to KCl, endothelin-1, and U-46619 increased with incubation but were
      unaffected by external pipping. In contrast, the contractions induced by
      norepinephrine, phenylephrine, and electric field stimulation decreased with
      development. No developmental changes were observed in endothelium-dependent
      [acetylcholine (ACh) and cyclopiazonic acid] or endothelium-independent [sodium
      nitroprusside (SNP)] relaxation. These relaxations were abolished by the soluble
      guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one.
      Endothelium-dependent relaxation was unaffected by blockade of cyclooxygenase or
      heme oxygenase but was significantly reduced by nitric oxide (NO) synthase
      inhibitors. Reduction of O2 concentration from 95 to 5% produced a marked
      reduction in ACh and SNP-induced relaxations. Chicken embryo pulmonary arteries
      show a marked endothelium-dependent relaxation that is unaffected by transition
      to ex ovo life. Endothelium-derived NO seems to be the main mediator responsible
      for this relaxation.

PMID- 11832416
TI  - Chronic measurement of cardiac output in conscious mice.
AB  - We describe the feasibility of chronic measurement of cardiac output (CO) in
      conscious mice. With the use of gas anesthesia, mice >30 g body wt were
      instrumented either with transit-time flow probes or electromagnetic probes
      placed on the ascending aorta. Ascending aortic flow values were recorded 6-16
      days after surgery when probes had fully grown in. In the first set of
      experiments, while mice were under ketamine-xylazine anesthesia, estimates of
      stroke volume (SV) obtained by the transit-time technique were compared with
      those simultaneously obtained by echocardiography. Transit-time values of SV were
      similar to those obtained by echocardiography. The average difference +/- SD
      between the methods was 2 +/- 7 microl. In the second set of studies, transit
      time values of CO were compared with those obtained by the electromagnetic flow
      probes. In conscious resting conditions, estimates +/- SD) of cardiac index (CI)
      obtained by the transit-time and electromagnetic flow probes were 484 +/- 119 and
      531 +/- 103 ml x min(-1) x kg body wt(-1), respectively. Transit-time flow probes
      were also implanted in mice with a myocardial infarction (MI) induced by ligation
      of a coronary artery 3 wk before probe implantation. In these MI mice (n = 7),
      average (+/- SD) resting and stimulated (by volume loading) values of CO were
      significantly lower than in noninfarcted mice (n = 15) (resting CO 16 +/- 3 vs.
      20 +/- 4 ml/min; stimulated CO 20 +/- 5 vs. 26 +/- 6 ml/min). Finally, using
      transfer function analysis, we found that, in resting conditions for both intact
      and MI mice, spontaneous variations in CO (> 0.1 Hz) were mainly due to those
      occurring in SV rather than in heart rate. These data indicate that CO can be
      measured chronically and reliably in conscious mice, also in conditions of heart
      failure, and that variations in preload are an important determinant of CO in
      this species.

PMID- 11832417
TI  - Prospect of a stanniocalcin endocrine/paracrine system in mammals.
AB  - Stanniocalcin (STC) is a calcium- and phosphate-regulating hormone produced in
      bony fish by the corpuscles of Stannius, which are located close to the kidney.
      It is a major antihypercalcemic hormone in fish. As the corpuscles of Stannius
      are absent, and antihypercalcemic hormones are basically not necessary, in
      mammals, the discovery of a mammalian homolog, STC1, was surprising and
      intriguing. STC1 displays a relatively high amino acid sequence identity
      (approximately 50%) with fish STC. In contrast to fish STC, STC1 is expressed in
      many tissues, including kidney. More recently, a human gene encoding the second
      stanniocalcin-like protein, STC2, was identified. STC2 has a lower identity
      (approximately 35%) with STC1 and fish STC. Similar to STC1, STC2 is also
      expressed in a variety of tissues. Research into the functions of STCs in mammals
      is still at an early stage, and the ultimate physiological and pathological roles
      of STCs have not yet been established. A few studies indicate that STC1, similar
      to fish STC, stimulates phosphate absorption in the kidney and intestine, but the
      function of STC2 is still unknown. However, several interesting findings have
      been reported on their cellular localization, gene structure, and expression in
      different physiological and pathological conditions, which will be clues in
      elucidating the functions of STCs in mammals. STC1 expression is enhanced by
      hypertonicity in a kidney cell line or by ischemic injuries and neural
      differentiation in the brain. STC1 expression in the ovary is also enhanced
      during pregnancy and lactation. Calcitriol upregulates STC1 and downregulates
      STC2 expression in the kidney. Interestingly, STC1 and STC2 are expressed in many
      tumor cell lines, and the expression of STC2 is enhanced by estradiol in breast
      cancer cells. STC2 is also expressed in pancreatic islets. These results suggest
      that the biological repertoires of STCs in mammals will be considerably larger
      than in fish and may not be limited to mineral metabolism. This brief review
      describes recent progress in mammalian STC research.

PMID- 11832418
TI  - Extracellular cAMP inhibits proximal reabsorption: are plasma membrane cAMP
      receptors involved?
AB  - Glucagon binding to hepatocytes has been known for a long time to not only
      stimulate intracellular cAMP accumulation but also, intriguingly, induce a
      significant release of liver-borne cAMP in the blood. Recent experiments have
      shown that the well-documented but ill-understood natriuretic and phosphaturic
      actions of glucagon are actually mediated by this extracellular cAMP, which
      inhibits the reabsorption of sodium and phosphate in the renal proximal tubule.
      The existence of this "pancreato-hepatorenal cascade" indicates that proximal
      tubular reabsorption is permanently influenced by extracellular cAMP, the
      concentration of which is most probably largely dependent on the insulin-to
      glucagon ratio. The possibility that renal cAMP receptors may be involved in this
      process is supported by the fact that cAMP has been shown to bind to brush-border
      membrane vesicles. In other cell types (i.e., adipocytes, erythrocytes, glial
      cells, cardiomyocytes), cAMP eggress and/or cAMP binding have also been shown to
      occur, suggesting additional paracrine effects of this nucleotide. Although not
      yet identified in mammals, cAMP receptors (cARs) are already well characterized
      in lower eukaryotes. The amoeba Dictyostelium discoideum expresses four different
      cARs during its development into a multicellular organism. cARs belong to the
      superfamily of seven transmembrane domain G protein-coupled receptors and exhibit
      a modest homology with the secretin receptor family (which includes PTH
      receptors). However, the existence of specific cAMP receptors in mammals remains
      to be demonstrated. Disturbances in the pancreato-hepatorenal cascade provide an
      adequate pathophysiological understanding of several unexplained observations,
      including the association of hyperinsulinemia and hypertension, the hepatorenal
      syndrome, and the hyperfiltration of diabetes mellitus. The observations reviewed
      in this paper show that cAMP should no longer be regarded only as an
      intracellular second messenger but also as a first messenger responsible for
      coordinated hepatorenal functions, and possibly for paracrine regulations in
      several other tissues.

PMID- 11832419
TI  - Distribution and oligomeric association of splice forms of Na(+)-K(+)-ATPase
      regulatory gamma-subunit in rat kidney.
AB  - Renal Na(+)-K(+)-ATPase is associated with the gamma-subunit (FXYD2), a single
      span membrane protein that modifies ATPase properties. There are two splice
      variants with different amino termini, gamma(a) and gamma(b). Both were found in
      the inner stripe of the outer medulla in the thick ascending limb.
      Coimmunoprecipitation with each other and the alpha-subunit indicated that they
      were associated in macromolecular complexes. Association was controlled by
      ligands that affect Na(+)-K(+)-ATPase conformation. In the cortex, the proportion
      of the gamma(b)-subunit was markedly lower, and the gamma(a)-subunit predominated
      in isolated proximal tubule cells. By immunofluorescence, the gamma(b)-subunit
      was detected in the superficial cortex only in the distal convoluted tubule and
      connecting tubule, which are rich in Na(+)-K(+)-ATPase but comprise a minor
      fraction of cortex mass. In the outer stripe of the outer medulla and for a short
      distance in the deep cortex, the thick ascending limb predominantly expressed the
      gamma(b)-subunit. Because different mechanisms maintain and regulate Na(+)
      homeostasis in different nephron segments, the splice forms of the gamma-subunit
      may have evolved to control the renal Na(+) pump through pump properties, gene
      expression, or both.

PMID- 11832420
TI  - Megalin is essential for renal proximal tubule reabsorption and accumulation of
      transcobalamin-B(12).
AB  - Megalin has previously been shown to bind and mediate endocytosis of
      transcobalamin (TC)-B(12). However, the physiological significance of this has
      not been established, and other TC-B(12) binding proteins have been suggested to
      mediate renal uptake of this vitamin complex. The present study demonstrates by
      the use of megalin-deficient mice that megalin is, in fact, essential for the
      normal renal reabsorption of TC-vitamin B(12) and for renal accumulation of this
      highly conserved vitamin. Megalin-deficient mice excrete increased amounts of TC
      and B(12) in the urine, revealing a defective renal tubular uptake of TC-B(12).
      The urinary B(12) excretion is increased approximately 4-fold, resulting in an
      approximately 28-fold higher renal B(12) clearance. This is associated with an
      approximately 4-fold decrease in B(12) content in megalin-deficient kidney
      cortex. Thus megalin is important to prevent urinary loss of vitamin B(12). In
      addition, light- and electron-microscopic immunocytochemistry demonstrate
      lysosomal accumulation of B(12) in rat and mouse proximal tubules. In rats this
      accumulation is correlated with vitamin intake. Thus renal lysosomal B(12)
      accumulation is dependent on vitamin status, indicating a possible reserve
      function of this organelle in the rat kidney.

PMID- 11832421
TI  - Protective effect of glycine on renal injury induced by ischemia-reperfusion in
      vivo.
AB  - Although glycine prevents renal tubular cell injury in vitro, its effect in vivo
      is not clear. The purpose of this study was to investigate whether a bolus
      injection of glycine given before reperfusion plus continuous dietary
      supplementation afterward would reduce renal injury caused by ischemia
      reperfusion. Female Sprague-Dawley rats received a semisynthetic powdered diet
      containing 5% glycine and 15% casein (glycine group) or 20% casein (control
      group). Two days later, renal ischemia was produced by cross-clamping the left
      renal vessels for 15 min, followed by reperfusion. The right kidney was removed
      before reperfusion. The postischemic glomerular filtration rate (GFR) showed that
      renal function was less impaired and recovered more quickly in rats receiving
      glycine. For example, at day 7, GFR in controls (0.31 +/- 0.03 ml x min(-1) x 100
      g(-1)) was about one-half that of glycine-treated rats (0.61 +/- 0.06 ml x min(
      1) x 100 g(-1), P < 0.05). Furthermore, tubular injury and cast formation
      observed in controls was minimized by glycine (pathology score, 3.2 +/- 0.4 vs.
      1.0 +/- 0.4, P < 0.05). Urinary lactate dehydrogenase (LDH) concentration was
      elevated by ischemia-reperfusion in the control group (260 +/- 22 U/l), but
      values were significantly lower by about fourfold (60 +/- 30 U/l) in glycine-fed
      rats. Similarly, free radical production in urine was significantly lower in
      glycine-treated animals. Importantly, on postischemic day 1, binding of
      pimonidazole, an in vivo hypoxia marker, was increased in the outer medulla in
      controls; however, this phenomenon was prevented by glycine. Two weeks later,
      mild leukocyte infiltration and interstitial fibrosis were still observed in
      controls, but not in kidneys from glycine-treated rats. In conclusion, these
      results indicate that administration of glycine indeed reduces mild ischemia
      reperfusion injury in the kidney in vivo, in part by decreasing initial damage
      and preventing chronic hypoxia.

PMID- 11832422
TI  - Interaction with grp58 increases activity of the thiazide-sensitive Na-Cl
      cotransporter.
AB  - The thiazide-sensitive sodium-chloride cotransporter (NCC) is expressed by distal
      convoluted tubule cells of the mammalian kidney. We used yeast two-hybrid
      screening to identify that glucose-regulated protein 58 (grp58), a protein
      induced by glucose deprivation, binds to the COOH terminus of the NCC.
      Immunoprecipitation of rat kidney cortex homogenates using a guinea pig anti-NCC
      antibody confirmed that grp58 associates with the NCC in vivo. Northern blots
      indicated that grp58 is highly expressed in rat kidney cortex. Immunofluorescence
      showed that grp58 protein abundance in kidney is highest in epithelial cells of
      the distal nephron, where it colocalizes with NCC near the apical membrane. To
      determine whether this interaction has a functional significance, NCC and grp58
      cRNA were coexpressed in Xenopus laevis oocytes. In oocytes overexpressing grp58,
      sodium uptake was increased compared with control. Because oocytes express
      endogenous grp58, antisense experiments were performed to evaluate whether
      endogenous grp58 affected NCC activity in oocytes. Sodium uptake was lower in
      oocytes injected with both antisense grp58 cRNA and sense NCC compared with sense
      NCC oocytes. Western blot analysis did not show any effect of grp58 expression on
      processing of the NCC. These data indicate a novel, functionally important
      interaction between grp58 and the NCC in rat kidney cortex.

PMID- 11832423
TI  - A role for Wnt-4 in renal fibrosis.
AB  - Wnt-4 is a secreted glycoprotein that is critical for genitourinary development
      but found only in the most distal collecting duct epithelium in the normal murine
      adult kidney. Wnt4 expression is induced throughout the collecting ducts in four
      murine models of renal injury that produce tubulointerstitial fibrosis: folic
      acid-induced nephropathy, unilateral ureteral obstruction, renal needle puncture,
      and genetic polycystic kidney disease. Wnt4 activation induced by injury is
      limited to collecting ducts, with initial activation in the collecting duct
      epithelium followed by activation in fibrotic lesions surrounding the collecting
      ducts. The highest cellular Wnt4 expression is in interstitial fibroblasts in the
      fibrotic lesions that also express high levels of collagen-alpha1(I) mRNA and
      alpha-smooth muscle actin. In support of a functional role for Wnt-4 in these
      activated myofibroblasts, Wnt-4 induces stabilization of cytosolic beta-catenin
      in a cultured myofibroblast cell line. Furthermore, Wnt-4-producing fibroblasts
      placed under the renal capsule of adult mice induce lesions with tubular
      epithelial destruction. These observations suggest a role for Wnt-4 in the
      pathogenesis of renal fibrosis.

PMID- 11832424
TI  - Altered regulation of SHP-2 and PTP 1B tyrosine phosphatases in cystic kidneys
      from bcl-2 -/- mice.
AB  - Protein tyrosine phosphorylation is a dynamic reversible process in which the
      level of phosphorylation, at any time, is the result of phosphatase and/or kinase
      activity. This balance is critical for control of growth and differentiation. The
      role of tyrosine phosphatases during nephrogenesis and in kidney disease requires
      delineation. Appropriate regulation of focal adhesion proteins such as focal
      adhesion kinase (FAK) and paxillin are important in cell adhesion, migration, and
      differentiation. We have previously shown that B cell lymphoma/leukemia-2 (bcl-2)
      -/- mice develop cystic kidneys and exhibit sustained phosphorylation of FAK and
      paxillin. We have examined the expression and activity of focal adhesion tyrosine
      phosphatases [Src homology-2 domain phosphatase (SHP-2), protein tyrosine
      phosphatase (PTP 1B), and PTP-proline, glutamate, serine, and threonine sequences
      (PEST)] during normal nephrogenesis and in cystic kidneys from bcl-2 -/- mice.
      Cystic kidneys from postnatal day 20 bcl-2 -/- mice demonstrate a reduced
      expression, sixfold decrease in activity, and altered distribution of SHP-2 and
      PTP 1B. PTP-PEST expression and distribution were similar in both bcl-2 +/+ and
      bcl-2 -/- mice. The altered regulation of PTP 1B and SHP-2 in kidneys from bcl-2 
      /- mice correlates with sustained phosphorylation of FAK and paxillin. Thus renal
      cyst formation in the bcl-2 -/- mice may be the result of an inability of
      complete differentiation due to continued activation of growth processes,
      including activation of FAK and paxillin.

PMID- 11832425
TI  - Analysis of NaCl transport in thin ascending limb of Henle's loop in CLC-K1 null
      mice.
AB  - To characterize the nature of NaCl transport in the thin ascending limb (tAL), we
      examined the transport properties of Na(+) and Cl(-) using in vitro
      microperfusion of the tAL in CLC-K1 null mice. In the presence of a transmural
      NaCl concentration gradient (100 mM higher in the lumen), the transepithelial
      diffusion voltage (V(d)) was 15.5 +/- 1.0 and -7.6 +/- 1.4 mV in CLC-K1(+/+) and
      CLC-K1(-/-) mice, respectively. Neither Cl(-) transport inhibitor 5-nitro-2-(3
      phenylpropylamino)-benzoate (NPPB) nor acidification of the bathing fluid changed
      the V(d) values in CLC-K1(-/-) mice. The addition of 300 microg/ml protamine, a
      selective blocker of paracellular conductance, to the bath increased the V(d)
      values by 5.6 +/- 0.7 and 12.6 +/- 1.5 mV (P < 0.001) in CLC-K1(+/+) and CLC-K1(
      /-) mice, respectively. Although efflux coefficients of (36)Cl were significantly
      decreased in CLC-K1(-/-) mice (188.3 +/- 25.6 in 4 tubules vs. 17.2 +/- 7.0 x 10(
      5) cm/s in 6 tubules), those of (22)Na were not different between CLC-K1(+/+) and
      CLC-K1(-/-) mice. These results clearly indicate that the major component of Cl(
      ) transport sensitive to NPPB or pH is mediated by CLC-K1 in the tAL.

PMID- 11832426
TI  - Role of NO in endothelin-regulated drug transport in the renal proximal tubule.
AB  - We previously demonstrated in intact killifish renal proximal tubules that
      endothelin (ET), acting through an ET(B) receptor and protein kinase C (PKC),
      reduced transport mediated by multidrug resistance-associated protein 2 (Mrp2),
      i.e., luminal accumulation of fluorescein methotrexate (FL-MTX) (Masereeuw R,
      Terlouw SA, Van Aubel RAMH, Russel FGM, and Miller DS. Mol Pharmacol 57: 59-67,
      2000). In the present study, we used confocal microscopy and quantitative image
      analysis to measure Mrp2-mediated transport of FL-MTX in killifish tubules as an
      indicator of the status of this ET-fired, intracellular signaling pathway.
      Exposing tubules to sodium nitroprusside (SNP), a nitric oxide (NO) donor,
      signaled a reduction in luminal accumulation of FL-MTX, which suggested pathway
      activation. N(G)-monomethyl-L-arginine (L-NMMA), an NO synthase inhibitor,
      blocked the action of ET-1 on transport. Because SNP effects on transport were
      blocked by bisindoylmaleide, a PKC-selective inhibitor, but not by RES-701-1, an
      ET(B)-receptor antagonist, generation of NO occurred after ET(B) receptor
      signaling but before PKC activation. NO generation was implicated in the actions
      of several nephrotoxicants, i.e., diatrizoate, gentamicin, amikacin, HgCl(2), and
      CdCl(2), each of which decreased Mrp2-mediated transport by activating ET
      signaling. For each nephrotoxicant, decreased FL-MTX transport was prevented when
      tubules were exposed to L-NMMA. ET-1 and each nephrotoxicant stimulated NO
      production by the tubules, as determined by a fluorescence-based assay. Together,
      the data show that NO generation follows ET binding to the basolateral ET(B)
      receptor and that, in activating the ET-signaling pathway, nephrotoxicants
      produce NO, a molecule that could contribute to subsequent toxic effects.

PMID- 11832427
TI  - Mechanism and regulation of vitamin B(6) uptake by renal tubular epithelia:
      studies with cultured OK cells.
AB  - The kidneys play an important role in regulating vitamin B(6) body homeostasis,
      but limited information exists regarding the mechanism of pyridoxine uptake by
      renal epithelial cells, and no study exists on its regulation. To address these
      issues, we used the renal opossum-derived tubular epithelial (opossum kidney; OK)
      cells and found pyridoxine uptake to 1) be temperature and energy dependent, 2)
      be pH dependent, with a higher uptake at alkaline or neutral buffer pH compared
      with acidic pH, 3) be Na(+) independent, 4) involve a saturable component
      (apparent Michaelis- Menten constant of 2.40 +/- 0.23 microM), 5) be inhibited by
      structural analogs, and 6) be amiloride sensitive. Maintaining OK cells in a
      vitamin B(6)-deficient growth medium (for 48 h) led to a significant upregulation
      of pyridoxine uptake. This upregulation was found to be specific for pyridoxine,
      inhibited by cyclohexamide and actinomycin D, reversible, and mediated via an
      increase in maximal velocity. Pretreating OK cells with modulates of a
      Ca(2+)/calmodulin-mediated pathway led to a significant downregulation in
      pyridoxine uptake via inhibition of maximal velocity. These results demonstrate
      that pyridoxine uptake by renal tubular epithelial OK cells is via a specialized
      pH-sensitive carrier-mediated mechanism. This mechanism appears to be regulated
      by extracellular vitamin B(6) levels and an intracellular Ca(2+)/calmodulin
      mediated pathway.

PMID- 11832428
TI  - Enhanced ammonia secretion by proximal tubules from mice receiving NH(4)Cl: role
      of angiotensin II.
AB  - Acidosis and angiotensin II (ANG II) stimulate ammonia production and transport
      by the proximal tubule. We examined the effect of short-term (18 h) in vivo acid
      loading with NH(4)Cl on ammonia production and secretion rates by mouse S2
      proximal tubule segments microperfused in vitro with or without ANG II in the
      luminal microperfusion solution. S2 tubules from NH(4)Cl-treated mice displayed
      higher rates of luminal ammonia secretion compared with those from control mice.
      The adaptive increase in ammonia secretion in NH(4)Cl-treated mice was eliminated
      when losartan was coadministered in vivo with NH(4)Cl. Ammonia secretion rates
      from both NH(4)Cl-treated and control mice were largely inhibited by amiloride.
      Addition of ANG II to the microperfusion solution enhanced ammonia secretion and
      production rates to a greater extent in tubules from NH(4)Cl-treated mice
      compared with those from controls, and the stimulatory effects of ANG II were
      blocked by losartan. These results demonstrate that a short-term acid challenge
      induces an adaptive increase in ammonia secretion by the proximal tubule and
      suggest that ANG II plays an important role in the adaptive enhancement of
      ammonia secretion that is observed with short-term acid challenges.

PMID- 11832429
TI  - Role of renal nerves in stimulation of renin, COX-2, and nNOS in rat renal cortex
      during salt deficiency.
AB  - We investigated a possible involvement of the sympathetic nervous system in the
      parallel increase of renin, cyclooxygenase-2 (COX-2), and neuronal nitric oxide
      synthase (nNOS) gene expression in the juxtaglomerular apparatus of rat kidneys
      induced by salt deficiency. Therefore, we determined the effects of renal
      denervation and the beta-adrenoreceptor antagonist metoprolol (50 mg/kg body wt
      po, twice a day) on renocortical expression of renin, COX-2, and nNOS in rats fed
      a low-salt (0.02% wt/wt) diet or treated for 1 wk with ramipril (10 mg/kg body
      wt) in combination with a low-salt diet. We found that a low-salt diet in
      combination with ramipril strongly increased renocortical mRNA levels of renin,
      COX-2, and nNOS 9-, 7-, and 2.5-fold, respectively. Treatment with metoprolol did
      not change basal expression of the three genes or induction of renin and COX-2
      gene expression, while induction of nNOS expression was clearly attenuated.
      Similarly, unilateral renal denervation attenuated induction of nNOS expression
      but had no effect on all other parameters. These findings suggest that beta
      adrenergic stimulation is not required for stimulation of renin and COX-2 gene
      expression in the juxtaglomerular apparatus during salt deficiency. However, beta
      adrenoreceptor activity or renal nerve activity appears to be required for the
      full stimulation of nNOS expression by low salt intake or combined with
      angiotensin-converting enzyme inhibition.

PMID- 11832430
TI  - ERK and p38 MAP kinase are involved in arachidonic acid release induced by
      H(2)O(2) and PDGF in mesangial cells.
AB  - Increased prostaglandin production is implicated in the pathogenesis of
      glomerular disease. With this consideration, we examined the combined effects of
      reactive oxygen species and platelet-derived growth factor (PDGF), which might
      initiate glomerular dysfunction, on arachidonic acid release and cytosolic
      phospholipase A(2) (cPLA(2)) activation in rat mesangial cells. H(2)O(2)-induced
      release of arachidonic acid was enhanced by PDGF, which by itself had little
      effect on the release, and the enhancement was completely inhibited by a cPLA(2)
      inhibitor. The phosphorylation of cPLA(2), extracellular signal-regulated kinase
      (ERK), and p38 mitogen-activated protein (MAP) kinase was upregulated by H(2)O(2)
      or PDGF alone and except for ERK was enhanced further by the two in combination.
      The release of arachidonic acid induced by PDGF together with H(2)O(2) was
      inhibited partially by an inhibitor of ERK or p38 MAP kinase and completely when
      the two inhibitors were combined; the inhibitory pattern was similar to that for
      the phosphorylation of cPLA(2). These results suggest that the ERK and p38 MAP
      kinase pathways are involved in the increase in cPLA(2) activation and
      arachidonic acid release induced by PDGF together with H(2)O(2).

PMID- 11832431
TI  - Segmental localization of mRNAs encoding Na(+)-K(+)-ATPase alpha(1)- and beta(1)
      subunits in diabetic rat kidneys using RT-PCR.
AB  - The present study evaluated renal Na(+)-K(+)-ATPase activity and mRNA in rats
      with diabetes mellitus. To localize the segmental alpha(1)- and beta(1)-mRNAs of
      Na(+)-K(+)-ATPase 1 and 8 days after induction of diabetes, we used the
      polymerase chain reaction after reverse transcription of the mRNA in
      microdissected nephron segments. Na(+)-K(+)-ATPase activity in the proximal
      convoluted tubule (PCT) rose on days 1 and 8 by 42 and 23%, respectively. In the
      medullary thick ascending limb (MTAL), it remained unchanged on day 1 and
      increased on day 8 by 55%. In the cortical collecting duct (CCD), activity rose
      by 81 and 45% on days 1 and 8, respectively. In parallel, alpha(1)-mRNA in the
      PCT increased by 52 and 22% on days 1 and 8, respectively. In the MTAL, alpha(1)
      mRNA remained unchanged on day 1 and rose by 47% on day 8. In the CCD, alpha(1)
      mRNA increased by 140 and 110% on days 1 and 8, respectively. beta(1)-mRNA was
      unchanged in the PCT throughout the study and was elevated in the MTAL and CCD on
      days 1 and 8. Thus there was a temporal dissociation between alpha(1)- and
      beta(1)-subunit expression. There was a highly significant linear correlation
      between Na(+)-K(+)-ATPase activity and alpha(1)-mRNA in all nephron segments
      throughout the experiment. It appears that microdissection of nephron tubules
      combined with reverse transcription-polymerase chain reaction defines the
      molecular identity of the amplified gene product and its segmental distribution
      in the nephron. We propose that altered gene expression may be the mechanism
      underlying enhanced Na(+) pump activity along the nephron in diabetic rats.

PMID- 11832432
TI  - ATP masks stretch activation of epithelial sodium channels in A6 distal nephron
      cells.
AB  - The mechanosensitivity of the epithelial sodium channel (ENaC) is controversial.
      Using cell-attached patch-clamp techniques, we found that mechanical stretch
      stimulated ENaC in A6 distal nephron cells in only three of nine cell-attached
      patches. However, stretch consistently activated ENaC after apical ATP was
      scavenged with apical hexokinase plus glucose or after P(2) receptors in the
      patch were blocked. The mean open probability (P(o)) of ENaC was increased from
      0.31 +/- 0.04 to 0.61 +/- 0.06 (P < 0.001; n = 9) when patch pipettes contained
      hexokinase and glucose, or from 0.24 +/- 0.05 to 0.55 +/- 0.11 (P < 0.01; n = 7)
      when patch pipettes contained suramin, respectively. A poorly hydrolyzable ATP
      analog, ATPgammaS, in the patch pipettes inhibited ENaC, reducing the P(o) from
      0.41 +/- 0.06 to 0.19 +/- 0.05 (P < 0.01; n = 8). Pretreatment of A6 cells with
      the phospholipase C (PLC) inhibitor U-73122 abolished the effect of ATP on ENaC
      activity. These data together suggest that ATP, acting through a PLC-dependent
      purinergic pathway, masks stretch-induced ENaC activation.

PMID- 11832433
TI  - Attenuated buffering of renal perfusion pressure variation in juxtamedullary
      cortex in SHR.
AB  - Renal tissue damage is substantially more pronounced in the juxtamedullary than
      in the superficial cortex in hypertensive rats, and the pathogenesis of the
      morphological changes are only partly understood. Glomerular capillary pressure
      (P(GC)) is increased, and steady-state autoregulation is normal in the deep renal
      cortex. We tested the hypothesis that the transient period from one pressure
      level to another may induce greater variation in local perfusion before stable
      autoregulation is established. An acute increase in local perfusion was compared
      in the superficial and juxtamedullary cortex of spontaneously hypertensive (SHR)
      and Wistar-Kyoto rats (WKY) after an abrupt increase in perfusion pressure. Total
      renal blood flow (RBF) was measured by a Transonic flow probe and local renal
      perfusion by laser Doppler flowmetry. Renal perfusion pressure was lowered to 50%
      of initial values and released abruptly. The maximal RBF increased from 6.3 +/-
      0.4 to a maximal value of 7.6 +/- 0.3 ml/min (P < 0.001) in SHR and from 7.3 +/-
      0.3 to 8.2 +/- 0.6 ml/min (P < 0.001) in WKY. These changes were not
      significantly different from each other. The change in superficial cortical
      perfusion was also not different between SHR and WKY. Pressure release increased
      juxtamedullary perfusion in SHR from 146 +/- 8 to a maximal value of 228 +/- 17
      units (P < 0.001) and in WKY from 160 +/- 13 to 179 +/- 11 units (P < 0.001). The
      results were significantly different from each other (P < 0.001). The time for
      maximal flow response was shorter in the deep cortex of SHR, and the time for
      normalization was longer than in WKY. These data indicate that the buffering of
      perfusion pressure variation is significantly attenuated in the juxtamedullary
      cortex, and significantly more so in SHR than in WKY, assuming a covariation of
      RBF and P(GC), and this finding may explain the extensive morphological damage in
      the juxtamedullary cortex of SHR.

PMID- 11832434
TI  - PTH and DA regulate Na-K ATPase through divergent pathways.
AB  - Parathyroid hormone (PTH) and dopamine (DA) inhibit Na-K ATPase activity and
      sodium-phosphate cotransport in proximal tubular cells. We previously showed that
      PTH and DA inhibit phosphate transport in opossum kidney (OK) cells through
      different signaling pathways. Therefore, we hypothesized that PTH and DA also
      inhibit Na-K ATPase through divergent pathways. We measured PTH and DA inhibition
      of Na-K ATPase activity in the presence of inhibitors of signaling pathways. PTH
      and DA inhibited Na-K ATPase in a biphasic manner, the early inhibition through
      protein kinase C (PKC)- and phospholipase A(2) (PLA(2))-dependent pathways and
      the late inhibition through protein kinase A- and PLA(2)-dependent pathways.
      Inhibition of extracellular signal-regulated kinase (ERK) activation blocked
      early and late inhibition of Na-K ATPase by PTH but not by DA. Pertussis toxin
      blocked early and late inhibition by DA but not by PTH. Treatment with DA, but
      not PTH, resulted in an early downregulation of basolateral membrane expression
      of the alpha-subunit, whereas total cellular expression remained constant for
      both agonists. We conclude that PTH and DA regulate Na-K ATPase by different
      mechanisms through activation of divergent pathways.

PMID- 11832435
TI  - Antigen retrieval reveals widespread basolateral expression of syntaxin 3 in
      renal epithelia.
AB  - Soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE)
      proteins play a key role in docking and fusion of intracellular transport
      vesicles and may regulate apical and basolateral membrane protein delivery in
      epithelial cells. In a previous study, syntaxin 3 (a target SNARE) protein was
      detectable in the kidney only in intercalated cells. We now report a more
      widespread distribution of syntaxin 3 in a variety of renal epithelial cells
      after antigen retrieval. Sections of rat kidney were treated with SDS and
      incubated with antisyntaxin 3 antibodies. Strong basolateral membrane staining
      was seen in descending and ascending thin limbs of Henle, thick ascending limbs
      of Henle, the macula densa, distal and connecting tubules, and all cells of the
      collecting duct including A- and B-intercalated cells. The papillary surface
      epithelium and the transitional epithelium of the ureter were also stained, but
      proximal tubules were negative. Western blotting revealed a strong signal at 37
      kDa in all regions, and the antigen was restricted to membrane fractions. SDS
      treatment was not necessary to reveal syntaxin 3 in intercalated cells. These
      data show that syntaxin 3 might be involved in basolateral trafficking pathways
      in most renal epithelial cell types. The exclusive basolateral location of
      syntaxin 3 in situ, however, contrasts with the apical location of this SNARE
      protein in some kidney epithelial cells in culture.

PMID- 11832436
TI  - Expression of urea transporters in the developing rat kidney.
AB  - Urea transport in the kidney is mediated by a family of transporter proteins that
      includes renal urea transporters (UT-A) and erythrocyte urea transporters (UT-B).
      Because newborn rats are not capable of producing concentrated urine, we examined
      the time of expression and the distribution of UT-A and UT-B in the developing
      rat kidney by light and electron microscopic immunocytochemistry. Kidneys from 16
      , 18-, and 20-day-old fetuses, 1-, 4-, 7-, 14-, and 21-day-old pups, and adult
      animals were studied. In the adult kidney, UT-A was expressed intensely in the
      inner medullary collecting duct (IMCD) and terminal portion of the short-loop
      descending thin limb (DTL) and weakly in long-loop DTL in the outer part of the
      inner medulla. UT-A immunoreactivity was not present in the fetal kidney but was
      observed in the IMCD and DTL in 1-day-old pups. The intensity of UT-A
      immunostaining in the IMCD gradually increased during postnatal development. In 4
      and 7-day-old pups, UT-A immunoreactivity was present in the DTL at the border
      between the outer and inner medulla. In 14- and 21-day-old pups, strong UT-A
      immunostaining was observed in the terminal part of short-loop DTL in the outer
      medulla, and weak labeling remained in long-loop DTL descending into the outer
      part of the inner medulla. In the adult kidney, there was intense staining for UT
      B in descending vasa recta (DVR) and weak labeling of glomeruli. In the
      developing kidney, UT-B was first observed in the DVR of a 20-day-old fetus.
      After birth there was a striking increase in the number of UT-B-positive DVR, in
      association with the formation of vascular bundles. The intensity of
      immunostaining remained strong in the outer medulla but gradually decreased in
      the inner medulla. We conclude that the expression of urea transporters in short
      loop DTL and DVR coincides with the development of the ability to produce a
      concentrated urine.

PMID- 11832437
TI  - Polaris, a protein disrupted in orpk mutant mice, is required for assembly of
      renal cilium.
AB  - Cilia are organelles that play diverse roles, from fluid movement to sensory
      reception. Polaris, a protein associated with cystic kidney disease in
      Tg737(o)(rpk) mice, functions in a ciliogenic pathway. Here, we explore the role
      of polaris in primary cilia on Madin-Darby canine kidney cells. The results
      indicate that polaris localization and solubility change dramatically during
      cilia formation. These changes correlate with the formation of basal bodies and
      large protein rafts at the apical surface of the epithelia. A cortical collecting
      duct cell line has been derived from mice with a mutation in the Tg737 gene.
      These cells do not develop normal cilia, which can be corrected by reexpression
      of the wild-type Tg737 gene. These data suggest that the primary cilia are
      important for normal renal function and/or development and that the ciliary
      defect may be a contributing factor to the cystic disease in Tg737(o)(rpk) mice.
      Further characterization of these cells will be important in elucidating the
      physiological role of renal cilia and in determining their relationship to cystic
      disease.

PMID- 11832439
TI  - Putting the spotlight on our most important discoveries.

PMID- 11832438
TI  - Immunomorphometric study of rat renal inner medulla.
AB  - We utilized immunofluorescent immunolabeling of renal tissue sections to identify
      and count tubules at specified depths of the rat renal inner medulla. We used
      primary antibodies to aquaporin-1 (AQP1; labeling thin descending limbs),
      aquaporin-2 (AQP2; labeling inner medullary collecting ducts), the rat kidney
      specific chloride channel (ClC-K1; labeling thin ascending limbs), and von
      Willebrand factor (labeling descending vasa recta). Secondary antibodies
      conjugated to different fluorophores were used, giving up to a three-color
      display. Labeled structures were then identified and counted. At each level
      sampled in the inner medulla, many more thin limbs were labeled by ClC-K1 than
      AQP1. In addition, thin limbs were found to label with antibodies to ClC-K1 on
      both sides of their hairpin turns. We conclude that the descending thin limbs
      shift from expressing AQP1 to expressing ClC-K1 some distance before the point
      where they turn and begin to ascend. Mathematical models can use our quantitative
      data to explore implications for the urine-concentrating mechanism.

PMID- 11832440
TI  - Vagal stimulation rapidly increases leptin secretion in human stomach.
AB  - BACKGROUND & AIMS: Leptin production has been reported in the rat and in human
      stomach. It initiates intestinal nutrient absorption. In this study, we analyzed
      the effect of vagal stimulation on leptin release in the human stomach. METHODS:
      We studied the secretion of gastric acid and leptin on stimulation with insulin
      (a stimulant of vagal pathways via hypoglycemia) and pentagastrin in 11 healthy
      men (normal endoscopy and normal histological gastric mucosa), 5 with previous
      highly selective vagotomy (HSV), and 6 without HSV. Fundic biopsies were
      performed for immunostaining of leptin. RESULTS: There was no difference between
      the 2 groups with respect to age, body mass index, basal leptin (4.8 +/- 1.2
      ng/15 minutes) and gastric acid (0.7 +/- 0.2 mmol/15 minutes) outputs. Leptin
      immunoreactivity was found in the fundic glands, and its distribution and density
      were similar in 2 groups. Insulin caused a rapid (15-minute) increase in leptin
      output in men without HSV (31 +/- 9 ng/15 minutes), but not in those with HSV
      (7.7 +/- 3.2 ng/15 minutes). Insulin-stimulated gastric leptin was biphasic, with
      a rapid increase (15 minutes after injection) followed by a second steady and
      sustained increase (39.9 +/- 7.6 ng/15 minutes at 120 minutes after injection).
      Pentagastrin increased gastric leptin output in individuals with (30 +/- 4.9
      ng/15 minutes) and without (26 +/- 3.2 ng/15 minutes) HSV. Insulin and
      pentagastrin did not modify plasma leptin, whatever HSV status. CONCLUSIONS:
      Vagal stimulation of leptin release in the human stomach suggests that leptin is
      released during the cephalic phase of gastric secretion. Luminal leptin may be
      involved in vagus-mediated intestinal functions.

PMID- 11832441
TI  - Selection of hepatitis B virus polymerase mutants with enhanced replication by
      lamivudine treatment after liver transplantation.
AB  - BACKGROUND & AIMS: Lamivudine has become a main therapeutic option for treating
      hepatitis B virus (HBV) infection. Although drug resistance develops, the
      clinical course after selection of antiviral-resistant HBV mutants seems to be
      benign. However, we observed a severe clinical course of hepatitis B infection in
      several liver transplant recipients after the emergence of lamivudine resistance.
      This was associated with high viral load in the blood. METHODS: In this report,
      we characterize the molecular mechanisms underlying drug-dependent enhanced
      replication of particular lamivudine-resistant HBV mutants selected in these
      patients, which were associated with sudden onset of liver failure. RESULTS: The
      clinical course was characterized by a sudden rise in serum bilirubin,
      prothrombin time, and transaminase. HBV sequence analysis of these patients
      revealed both mutations in the "a-determinant" of the envelope and the YMDD
      (tyrosine, methionine, aspartate, aspartate) motif (domain C) of the polymerase
      protein. Transfection experiments with replication competent vectors indicated
      that the "a-determinant" changes were not associated with resistance, whereas
      mutations in the YMDD motif conferred resistance to lamivudine. More importantly,
      combinations of mutations in the "a-determinant" and the YMDD motif in patients
      with a severe hepatitis were not only resistant to lamivudine treatment, but
      showed enhanced replication in vitro in the presence of lamivudine. This
      observation was confirmed in separate laboratories. CONCLUSIONS: Severe and fatal
      hepatitis B infection can occur during lamivudine therapy and may be associated
      with certain HBV mutants selected during sequential nucleoside and HBIg
      treatment. The lamivudine-enhanced replication shown by these mutants suggests
      that continuation of therapy with lamivudine could be deleterious in some
      patients.

PMID- 11832442
TI  - Tumor necrosis factor alpha promoter polymorphisms and insulin resistance in
      nonalcoholic fatty liver disease.
AB  - BACKGROUND & AIMS: Nonalcoholic fatty liver disease, which can range from fatty
      liver alone to nonalcoholic steatohepatitis and cirrhosis, is related to insulin
      resistance. Tumor necrosis factor alpha (TNF-alpha) may induce insulin
      resistance, and polymorphisms of its promoter have been associated with an
      increased release of this cytokine. We analyzed (1) the prevalence of insulin
      resistance, (2) the prevalence of the 238 and 308 TNF-alpha polymorphisms, and
      (3) the relationship among TNF-alpha polymorphisms, insulin resistance, and the
      occurrence of steatohepatitis in 99 patients with nonalcoholic fatty liver
      diagnosed by ultrasonography and confirmed by histologic analysis in the 53 who
      underwent biopsy. METHODS: Insulin resistance was evaluated by the homeostatic
      metabolic assessment insulin resistance indices and TNF-alpha polymorphisms by
      polymerase chain reaction and restriction fragment length polymorphism analysis.
      RESULTS: Insulin resistance was detected in almost all of the patients and was
      more severe in those with steatohepatitis. The prevalence of the 238, but not of
      the 308, TNF-alpha polymorphism was higher in subjects with nonalcoholic fatty
      liver than in controls (31% vs. 15%; P < 0.0001), and patients positive for TNF
      alpha polymorphisms had higher insulin resistance indices, a higher prevalence of
      impaired glucose tolerance, and a lower number of associated risk factors for
      steatosis. CONCLUSIONS: TNF-alpha polymorphisms could represent a susceptibility
      genotype for insulin resistance, nonalcoholic fatty liver, and steatohepatitis.

PMID- 11832443
TI  - Excess alcohol greatly increases the prevalence of cirrhosis in hereditary
      hemochromatosis.
AB  - BACKGROUND & AIMS: The progression of fibrosis to cirrhosis is the most
      significant prognostic factor in hereditary hemochromatosis. We aimed to
      determine the range of hepatic iron concentration associated with cirrhosis in
      the absence of alcohol and other pro-fibrogenic cofactors and to quantify the
      contribution of excess alcohol consumption to the development of cirrhosis.
      METHODS: Liver biopsy data were evaluated on 224 C282Y homozygous hemochromatosis
      subjects. To determine the effect of alcohol alone on the development of
      fibrosis, subjects with viral hepatitis or nonalcoholic steatohepatitis were
      excluded. Subjects were divided into those who consumed less than 60 g alcohol
      per day and those who consumed 60 g per day or more. RESULTS: Seven percent of
      subjects who consumed less than 60 g per day had severe fibrosis/cirrhosis
      compared with 61% of excess alcohol consumers. CONCLUSIONS: Hemochromatosis
      subjects who drink more than 60 g alcohol per day are approximately 9 times more
      likely to develop cirrhosis than those who drink less than this amount, and the
      range of hepatic iron concentration associated with cirrhosis in the absence of
      cofactors was 233-675 micromol/g dry weight.

PMID- 11832444
TI  - Cerebral cortical registration of subliminal visceral stimulation.
AB  - BACKGROUND & AIMS: Although brain registration of subliminal somatic stimulations
      such as masked visual stimuli and their influence on electrical and hemodynamic
      measures of cerebral activity have been reported previously, there have been no
      reports on cerebral cortical registration of subliminal visceral stimulation.
      Because studies evaluating the consequences of subliminal somatic stimulation
      have shown that subliminal stimulation can effect behavior, it is conceivable
      that such subliminal messages from the intestine could potentially influence
      intestinal sensory/motor function or effect the perception/interpretation of
      sensory signals originating from the gut. METHODS: We studied the cerebral
      cortical functional magnetic resonance imaging (fMRI) response to subliminal,
      liminal, and supraliminal rectal distention in healthy volunteers. RESULTS: Study
      findings indicate that subliminal afferent signals originating from the gut are
      registered in the cerebral cortex without reaching the level of awareness.
      Locations of cortical activity caused by intestinal subliminal stimulation are
      similar to those of liminal and supraliminal stimulation but their intensity and
      volume are significantly lower (P < 0.05). CONCLUSIONS: Subliminal afferent
      signals originating from the gut are registered in the cerebral cortex and induce
      changes in measures of brain activity, such as hemodynamic changes detectable by
      fMRI.

PMID- 11832445
TI  - Acid exposure activates the mitogen-activated protein kinase pathways in
      Barrett's esophagus.
AB  - BACKGROUND & AIMS: To explore mechanisms whereby acid reflux might contribute to
      carcinogenesis in Barrett's esophagus (BE) we studied: (1) the effects of acid on
      the mitogen-activated protein kinase (MAPK) pathways, cell proliferation, and
      apoptosis in a Barrett's adenocarcinoma cell line (SEG-1); and (2) the ability of
      acid to activate the MAPK pathways in vivo in patients with BE. METHODS: SEG-1
      cells were exposed to acidic media for 3 minutes, and the activities of 3 MAPKs
      (ERK, p38, and JNK) were determined. Proliferation was assessed using flow
      cytometry; cell growth and apoptosis were assessed using cell counts and an
      apoptosis ELISA assay. MAPK activation was studied in biopsy specimens taken from
      patients with BE before and after esophageal perfusion for 3 minutes with 0.1N
      HCl. RESULTS: Acid-exposed SEG-1 cells exhibited a significant increase in
      proliferation and total cell numbers, and a significant decrease in apoptosis.
      These effects were preceded by a rapid increase in the activities of ERK and p38,
      and a delayed increase in JNK activity. PD 98059 abolished the acid-induced
      increase in G0/G1 and decrease in subG0 phases of the cell cycle. Both SB 203580
      and DN-JNK 1/2 inhibited the acid-induced progression from G0/G1 to G2/M. The
      acid-induced decrease in apoptosis was abolished by inhibition of either ERK or
      p38. In the patients, acid exposure significantly increased the activity of p38
      in the metaplastic epithelium. CONCLUSIONS: Acid increases proliferation and
      survival, and decreases apoptosis in SEG-1 cells by activating the MAPK pathways.
      Acid also activates the MAPK pathways in BE in vivo. These findings suggest that
      acid might contribute to carcinogenesis in BE through activation of MAPK
      pathways.

PMID- 11832446
TI  - 3-hydroxy-3-methylglutaryl-coenzyme a reductase inhibitors reduce human
      pancreatic cancer cell invasion and metastasis.
AB  - BACKGROUND & AIMS: Inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA)
      reductase blocks the mevalonate metabolic pathway, which is necessary for the
      isoprenylation of a number of small guanosine triphosphatases. We examined the
      effects of HMG-CoA reductase inhibitors, fluvastatin and lovastatin, on human
      pancreatic cancer cell invasion in vitro and experimental liver metastasis in
      vivo. METHODS: Cell invasion was studied in a modified Boyden chamber assay. The
      translocation of RhoA was assessed by immunoblotting. Experimental liver
      metastases were induced in nude mice by intrasplenic inoculation of ASPC-1 human
      pancreatic cancer cells. RESULTS: Fluvastatin and lovastatin inhibited the in
      vitro cancer cell invasion induced by epidermal growth factor (EGF) in a manner
      sensitive to C3 transferase, a specific inhibitor of Rho. Treatment of ASPC-1
      cells with fluvastatin markedly attenuated the EGF-induced translocation of RhoA
      from the cytosol to the membrane fraction and caused cell rounding. The effects
      of fluvastatin could be reversed by the addition of all-trans-geranylgeraniol.
      Administration of fluvastatin to nude mice reduced both metastatic tumor
      formation in the liver and the growth of established liver metastases at doses
      recommended for the treatment of hypercholesterolemia in humans. CONCLUSIONS: HMG
      CoA reductase inhibitors can be antimetastatic agents with the potential for
      useful clinical applications.

PMID- 11832447
TI  - Carbon dioxide affects rat colonic Na+ absorption by modulating vesicular
      traffic.
AB  - BACKGROUND & AIMS: We examined whether CO2 affects colonic Na+ absorption by
      endosome recycling of the Na+/H+ exchanger NHE3. METHODS: Rat distal colon
      segments exposed to various acid-base conditions were examined by transmission
      electron microscopy at 27,500x magnification and subapical vesicles quantified.
      Immunocytochemistry was used to identify vesicular NHE3. Endocytosis was tested
      for by observing internalization of apical membrane labeled with fluorescein
      isothiocyanate-phytohemagglutinin and Cy-3-NHE3 antibody using confocal
      microscopy. The effects of mucosal 5-(N,N-dimethyl)-amiloride (DMA), which
      inhibits NHE2 and/or NHE3, and wortmannin, which inhibits phosphatidylinositol 3
      kinase, on CO2-stimulated Na+ absorption were measured in the Ussing chamber.
      RESULTS: The number of (coated and uncoated) subapical vesicles in epithelial
      cells was specifically and inversely related to net colonic Na+ absorption and
      PCO2. Immunoperoxidase labeling localized NHE3 on microvilli and vesicle
      membranes. Under the confocal microscope, a fluorescent band along apical
      membranes at PCO2 70 mm Hg became a subapical haze at PCO2 21 mm Hg. This pattern
      was not affected by carbonic anhydrase inhibition or when pH or [HCO3-] was
      changed, but PCO2 was held constant. DMA inhibition indicated that NHE3 mediates
      CO2-stimulated Na+ absorption. Wortmannin inhibited CO2-stimulated vesicle
      movement (exocytosis) and Na+ absorption. CONCLUSIONS: CO2 affects Na+ absorption
      in rat distal colon epithelium in part by modulating the movement of NHE3
      containing vesicles to and from the apical membrane.

PMID- 11832448
TI  - Tumor necrosis factor alpha stimulates invasion of Src-activated intestinal
      cells.
AB  - BACKGROUND & AIMS: Src activation is correlated with progression of colorectal
      cancer (CRC). CRCs accompanied by ulcerative colitis, chronic inflammation in the
      colon, often have elevated Src activity, and ulcerative colitis-related CRCs are
      more likely to become invasive, whereas Ras activation is rarely associated with
      this disease. The aim of this study was to investigate the effects of a
      proinflammatory cytokine, tumor necrosis factor alpha (TNF-alpha), on the
      invasive properties of epithelial cells constitutively expressing activated Ras
      or Src. METHODS: A cell line derived from intestinal epithelia was transfected
      with a v-src- or v-H-ras-expressing vector. The effect of TNF-alpha on
      morphologic changes in colonies cultured in soft agar was determined. Src protein
      kinase activity, peroxide production, E-cadherin expression levels, and the
      phosphorylation status of beta-catenin and E-cadherin were determined. The
      invasive potential of these cells was determined by measuring cell motility and
      using an in vitro invasion assay. RESULTS: TNF-alpha altered the colony
      morphology of src-, but not ras-expressing cells. TNF-alpha increased peroxide
      production, leading to Src protein expression as well as Src activity in src
      transfectants. Activation of Src by TNF-alpha led to reduced E-cadherin levels
      and enhanced invasion of src transfectants. Pyrrolidine dithiocarbamate and
      herbimycin A inhibited these effects. CONCLUSION: These results indicate that Src
      kinase activation enhances the response of epithelial cells to TNF-alpha leading
      to increased invasion through mechanisms that involve production of reactive
      oxygen intermediates.

PMID- 11832449
TI  - Opioid agonists inhibit excitatory neurotransmission in ganglia and at the
      neuromuscular junction in Guinea pig gallbladder.
AB  - BACKGROUND & AIMS: Opiates administered therapeutically could have an inhibitory
      effect on the neuromuscular axis of the gallbladder, and thus contribute to
      biliary stasis and acalculous cholecystitis. METHODS: Intracellular recordings
      were made from gallbladder neurons and smooth muscle, and tension measurements
      were made from muscle strips. Opioid receptor-specific agonists tested: delta,
      DPDPE; kappa, U-50488H; and mu, DAMGO. RESULTS: Opioid agonists had no effect on
      gallbladder neurons or smooth muscle. Each of the opioid agonists potently
      suppressed the fast excitatory synaptic input to gallbladder neurons, in a
      concentration-dependent manner with half-maximal effective concentration values
      of about 1 pmol/L. Also, each agonist caused a concentration-dependent reduction
      in the amplitude of the neurogenic contractile response (half-maximal effective
      concentration values: DPDPE, 189 pmol/L; U-50488H, 472 pmol/L; and DAMGO, 112
      pmol/L). These ganglionic and neuromuscular effects were attenuated by the highly
      selective opioid-receptor antagonist, naloxone. Opioid-receptor activation also
      inhibited the presynaptic facilitory effect of cholecystokinin in gallbladder
      ganglia. Immunohistochemistry with opioid receptor-specific antisera revealed
      immunostaining for all 3 receptor subtypes in nerve bundles and neuronal cell
      bodies within the gallbladder, whereas opiate-immunoreactive nerve fibers are
      sparse in the gallbladder. CONCLUSIONS: These results show that opiates can cause
      presynaptic inhibition of excitatory neurotransmission at 2 sites within the wall
      of the gallbladder: vagal preganglionic terminals in ganglia and neuromuscular
      nerve terminals. These findings support the concept that opiates can contribute
      to gallbladder stasis by inhibiting ganglionic activity and neurogenic
      contractions.

PMID- 11832450
TI  - Steatosis and liver cancer in transgenic mice expressing the structural and
      nonstructural proteins of hepatitis C virus.
AB  - BACKGROUND & AIMS: The aim of this study was to determine whether expression of
      hepatitis C virus proteins alters hepatic morphology or function in the absence
      of inflammation. METHODS: Transgenic C57BL/6 mice with liver-specific expression
      of RNA encoding the complete viral polyprotein (FL-N transgene) or viral
      structural proteins (S-N transgene) were compared with nontransgenic littermates
      for altered liver morphology and function. RESULTS: FL-N transcripts were
      detectable only by reverse-transcription polymerase chain reaction, and S-N
      transcripts were identified in Northern blots. The abundance of viral proteins
      was sufficient for detection only in S-N transgenic animals. There was no
      inflammation in transgenic livers, but mice expressing either transgene developed
      age-related hepatic steatosis that was more severe in males. Apoptotic or
      proliferating hepatocytes were not significantly increased. Hepatocellular
      adenoma or carcinoma developed in older male animals expressing either transgene,
      but their incidence reached statistical significance only in FL-N animals.
      Neither was ever observed in age-matched nontransgenic mice. CONCLUSIONS:
      Constitutive expression of viral proteins leads to common pathologic features of
      hepatitis C in the absence of specific anti-viral immune responses. Expression of
      the structural proteins enhances a low background of steatosis in C57BL/6 mice,
      while additional low level expression of nonstructural proteins increases the
      risk of cancer.

PMID- 11832451
TI  - Mitochondrial injury, oxidative stress, and antioxidant gene expression are
      induced by hepatitis C virus core protein.
AB  - BACKGROUND & AIMS: The mechanisms of liver injury in chronic hepatitis C virus
      (HCV) infection are poorly understood. Indirect evidence suggests that oxidative
      stress and mitochondrial injury play a role. The aim of this study was to
      determine if the HCV core protein itself alters mitochondrial function and
      contributes to oxidative stress. METHODS: HCV core protein was expressed in 3
      different cell lines, and reactive oxygen species (ROS) and lipid peroxidation
      products were measured. RESULTS: Core expression uniformly increased ROS. In 2
      inducible expression systems, core protein also increased lipid peroxidation
      products and induced antioxidant gene expression as well. A mitochondrial
      electron transport inhibitor prevented the core-induced increase in ROS. A
      fraction of the expressed core protein localized to the mitochondria and was
      associated with redistribution of cytochrome c from mitochondrial to cytosolic
      fractions. Sensitivity to oxidative stress was also seen in HCV transgenic mice
      in which increased intrahepatic lipid peroxidation products occurred in response
      to carbon tetrachloride. CONCLUSIONS: Oxidative injury occurs as a direct result
      of HCV core protein expression both in vitro and in vivo and may involve a direct
      effect of core protein on mitochondria. These results provide new insight into
      the pathogenesis of hepatitis C and provide an experimental rationale for
      investigation of antioxidant therapy.

PMID- 11832452
TI  - Aminopeptidase N is involved in cell motility and angiogenesis: its clinical
      significance in human colon cancer.
AB  - BACKGROUND & AIMS: The molecular basis of cell motility is highly complex and is
      controlled by a number of molecular systems, whereas angiogenesis is an important
      biological component of tumor progression. The aims of this study were to
      investigate the possible involvement of proteins at the cell surface in
      controlling cell motility and angiogenesis, and to identify the cell surface
      molecules involved in gastrointestinal tumors. METHODS: We addressed these issues
      using functional monoclonal antibodies, which inhibit cell motility, endothelial
      cell migration, and tube formation. Furthermore, we investigated the relationship
      between this antigen and colon cancer, and showed the prognostic significance in
      human colon cancer. RESULTS: We established a murine monoclonal antibody MH8-11,
      which inhibits cell motility and in vitro angiogenesis. This epitope was a 165
      kilodalton protein, and the sequencing analysis revealed that it was almost
      identical to aminopeptidase N (APN)/cluster of differentiation (CD) 13. APN/CD13
      expression was associated with tumor status (P = 0.025). The disease-free and
      overall survival rate for patients with positive APN/CD13 expression tumors was
      significantly lower than that for patients with negative APN/CD13 expression
      tumors (P = 0.014, 0.033, respectively). Among 47 node-positive patients, the
      survival rate of patients with negative APN/CD13 expression was better than that
      of those with positive APN/CD13 expression. CONCLUSIONS: Our data suggest that
      APN/CD13 is involved in cell motility and angiogenesis, and APN/CD13 expression
      may be a useful indicator of a poor prognosis for node-positive patients with
      colon cancer.

PMID- 11832453
TI  - 5-lipoxygenase inhibition reduces intrahepatic vascular resistance of cirrhotic
      rat livers: a possible role of cysteinyl-leukotrienes.
AB  - BACKGROUND & AIMS: Cysteinyl-leukotrienes (Cys-LTs) increase intrahepatic
      vascular resistance in normal rat livers. CCl4 cirrhotic rat livers have
      increased Cys-LT production and 5-lipoxygenase messenger RNA (mRNA) expression.
      The aim of this study was to investigate the role of 5-lipoxygenase-derived
      eicosanoids regulating intrahepatic vascular tone in control and CCl4-induced
      cirrhotic rat livers. METHODS: In different groups of portally perfused control
      and cirrhotic rat livers, the following were analyzed: a portal perfusion
      pressure (PP) dose-response curve to LTD4; the effects on PP caused by either
      vehicle, the selective 5-lipoxygenase inhibitor AA-861, the selective Cys-LT1
      receptor antagonist MK-571, or the dual Cys-LT1 and Cys-LT2 receptor antagonist
      BAY u9773; and immunohistochemistry for 5-lipoxygenase in liver sections of
      cirrhotic and control livers. RESULTS: Cirrhotic livers have a hyperesponse to
      LTD4. In control livers, AA-861 and MK-571 produced a moderate and similar
      reduction in PP. In cirrhotic livers, 5-lipoxygenase inhibition produced a marked
      and significantly greater reduction in PP than in controls. However, no effect on
      PP was observed after MK-571 or BAY u9773. 5-Lipoxygenase-positive cells were
      markedly increased in cirrhotic livers. CONCLUSIONS: Our results suggest that 5
      lipoxygenase-derived eicosanoids may contribute to the increased intrahepatic
      vascular resistance of cirrhotic rat livers and therefore the pathogenesis of
      portal hypertension.

PMID- 11832454
TI  - Experimental ulcers alter voltage-sensitive sodium currents in rat gastric
      sensory neurons.
AB  - BACKGROUND & AIMS: Voltage-dependent Na+ currents are important determinants of
      excitability. We hypothesized that gastric inflammation alters Na+ current
      properties in primary sensory neurons. METHODS: The stomach was surgically
      exposed in rats to inject the retrograde tracer 1.1'-dioctadecyl-3,3,3,'3
      tetramethylindocarbocyanine methanesulfonate and saline (control) or 20% acetic
      acid (ulcer group) into the gastric wall. Nodose or thoracic dorsal root ganglia
      (DRG) were harvested after 7 days to culture neurons and record Na+ currents
      using patch clamp techniques. RESULTS: There were no lesions in the control and 3
      +/- 1 ulcers in the ulcer group. Na+ currents recovered significantly more
      rapidly from inactivation in nodose and DRG neurons obtained from animals in the
      ulcer group compared with controls. This was partially a result of an increase in
      the relative contribution of the tetrodotoxin-resistant to the peak sodium
      current. In addition, the recovery kinetics of the tetrodotoxin-sensitive current
      were faster. In DRG neurons, gastric inflammation shifted the voltage-dependence
      of activation of the tetrodotoxin-resistant current to more hyperpolarized
      potentials. CONCLUSIONS: Gastric injury alters the properties of Na+ currents in
      gastric sensory neurons. This may enhance excitability, thereby contributing to
      the development of dyspeptic symptoms.

PMID- 11832455
TI  - Detection of dysplastic intestinal adenomas using enzyme-sensing molecular
      beacons in mice.
AB  - BACKGROUND & AIMS: Proteases play key roles in the pathogenesis of tumor growth
      and invasion. This study assesses the expression of cathepsin B in dysplastic
      adenomatous polyps. METHODS: Aged Apc(Min/+) mice served as an experimental model
      for familial adenomatous polyposis. The 4 experimental groups consisted of (a)
      animals injected with a novel activatable, cathepsin B sensing near infrared
      fluorescence (NIRF) imaging probe; (b) animals injected with a nonspecific NIRF;
      (c) uninjected control animals; and (d) non-APC(Min/+) mice injected with the
      cathepsin B probe. Lesions were analyzed by immunohistochemistry, Western
      blotting, reverse transcription-polymerase chain reaction, and optical imaging.
      RESULTS: Cathepsin B was consistently overexpressed in adenomatous polyps. When
      mice were injected intravenously with the cathepsin reporter probe, intestinal
      adenomas became highly fluorescent indicative of high cathepsin B enzyme
      activity. Even microscopic adenomas were readily detectable by fluorescence, but
      not light, imaging. The smallest lesion detectable measured 50 microm in
      diameter. Adenomas in the indocyanine green and/or noninjected group were only
      barely detectable above the background. CONCLUSIONS: The current experimental
      study shows that cathepsin B is up-regulated in a mouse model of adenomatous
      polyposis. Cathepsin B activity can be used as a biomarker to readily identify
      such lesions, particularly when contrasted against normal adjacent mucosa. This
      detection technology can be adapted to endoscopy or tomographic optical imaging
      methods for screening of suspicious lesions and potentially for molecular
      profiling in vivo.

PMID- 11832456
TI  - Ca2+ waves require sequential activation of inositol trisphosphate receptors and
      ryanodine receptors in pancreatic acini.
AB  - BACKGROUND & AIMS: The inositol 1,4,5-trisphosphate (InsP3) receptor (InsP3R) and
      the ryanodine receptor (RyR) are the principal Ca2+-release channels in cells and
      are believed to serve distinct roles in cytosolic Ca2+ (Ca(i)2+) signaling. This
      study investigated whether these receptors instead can release Ca2+ in a
      coordinated fashion. METHODS: Apical and basolateral Ca(i)2+ signals were
      monitored in rat pancreatic acinar cells by time-lapse confocal microscopy. Caged
      forms of second messengers were microinjected into individual cells and then
      photoreleased in a controlled fashion by either UV or 2-photon flash photolysis.
      RESULTS: InsP3 increased Ca(i)2+ primarily in the apical region of pancreatic
      acinar cells, whereas the RyR agonist cyclic adenosine diphosphate ribose (cADPR)
      increased Ca(i)2+ primarily in the basolateral region. Apical-to-basal Ca(i)2+
      waves were induced by acetylcholine and initiation of these waves was blocked by
      the InsP3R inhibitor heparin, whereas propagation into the basolateral region was
      inhibited by the cADPR inhibitor 8-amino-cADPR. To examine integration of apical
      and basolateral Ca(i)2+ signals, Ca2+ was selectively released either apically or
      basolaterally using 2-photon flash photolysis. Ca(i)2+ increases were transient
      and localized in unstimulated cells. More complex Ca(i)2+ signaling patterns,
      including polarized Ca(i)2+ waves, were observed when Ca2+ was photoreleased in
      cells stimulated with subthreshold concentrations of acetylcholine. CONCLUSIONS:
      Polarized Ca(i)2+ waves are induced in acinar cells by serial activation of
      apical InsP3Rs and then basolateral RyRs, and subcellular release of Ca2+
      coordinates the actions of these 2 types of Ca2+ channels. This subcellular
      integration of Ca2+-release channels shows a new level of complexity in the
      formation of Ca(i)2+ waves.

PMID- 11832457
TI  - Expression of CCK2 receptors in the murine pancreas: proliferation,
      transdifferentiation of acinar cells, and neoplasia.
AB  - BACKGROUND & AIMS: To explore the pancreatic function of CCK2/gastrin receptor,
      we created ElasCCK2 transgenic mice expressing the human receptor in pancreatic
      exocrine cells. In previous studies, the transgenic CCK2/gastrin receptor was
      demonstrated to mediate enzyme release and protein synthesis. We now report
      results of phenotypic and long-term studies. METHODS: Pancreas was characterized
      using morphometry and immunohistochemistry. ElasCCK2 mice were crossed with INS
      GAS mice expressing gastrin in pancreatic beta cells to achieve continuous
      stimulation of the CCK2/gastrin receptor. RESULTS: The pancreatic weight of
      ElasCCK2 mice was increased by 40% and correlated with an increase in the area of
      exocrine tissue. Alterations in pancreatic histology were apparent from postnatal
      day 50. Crossing the ElasCCK2 mice with INS-GAS mice resulted in development of
      morphologic changes in younger animals. Malignant transformation occurred in 3 of
      20 homozygous ElasCCK2 mice. Although tumors had different phenotypes, they all
      developed through an acinar-ductal carcinoma sequence. CONCLUSIONS: Our data show
      that transgenic expression of a G protein-coupled receptor can lead to cancer.
      This study also supports a key role of the CCK2/gastrin receptor in the
      development of pre- and neoplastic lesions of the pancreas. ElasCCK2 mice provide
      a model for carcinogenesis by transformation and dedifferentiation of acinar
      cells.

PMID- 11832458
TI  - Early cell transplantation in LEC rats modeling Wilson's disease eliminates
      hepatic copper with reversal of liver disease.
AB  - BACKGROUND & AIMS: The Long-Evans Cinnamon (LEC) rat is an excellent model of
      Wilson's disease with impaired copper excretion, hypoceruloplasminemia, and
      copper toxicosis. We hypothesized that early hepatocyte transplantation would
      improve copper excretion and liver disease in Wilson's disease. METHODS: Normal
      syngeneic Long-Evans Agouti rat hepatocytes were transplanted intrasplenically
      into 2-week-old LEC rats. Untreated LEC pups were controls. Liver repopulation
      was shown by changes in serum ceruloplasmin, hepatic atp7b messenger RNA, and
      bile and liver copper levels. Histologic analysis of the liver was performed.
      RESULTS: Significant copper accumulation and liver disease were observed in 5
      month-old LEC rats, with occasional treated rats showing increased bile copper
      excretion. The liver was repopulated extensively in 10 of 14 treated LEC rats
      (71%) 20 months after cell transplantation. In these 10 rats, hepatic copper
      content was virtually normal in 6 rats (53 +/- 12 microg/g liver) and
      substantially less in 4 others (270 +/- 35 microg/g) compared with elevated liver
      copper levels in untreated LEC rats (1090 +/- 253 microg/g) (P < 0.001). Changes
      in serum ceruloplasmin levels, bile copper excretion capacity, and liver
      histology were in concordance with decreases in liver copper levels. CONCLUSIONS:
      Transplanted cells proliferated subsequent to the onset of liver injury, and the
      liver was repopulated over an extended period. Cell transplantation eventually
      restored copper homeostasis and reversed liver disease without hepatic
      preconditioning in LEC rats.

PMID- 11832459
TI  - NF-kappaB activation in pancreas induces pancreatic and systemic inflammatory
      response.
AB  - BACKGROUND & AIMS: The role of nuclear factor kappaB (NF-kappaB) activation in
      acute pancreatitis is uncertain. The transcription factor NF-kappaB is activated
      early in acute pancreatitis, and NF-kappaB is widely considered a key element in
      inflammatory responses based on its ability to regulate the expression of
      inflammatory mediators in vitro. However, its role in vivo in specific diseases
      remains unclear, and the current data on the role of NF-kappaB in acute
      pancreatitis is primarily correlative. METHODS: In this study, NF-kappaB was
      directly activated within the pancreas using adenoviral-mediated transfer of an
      active subunit, RelA/p65 (Adp65), delivered by intraductal injection. RESULTS:
      Administration of Adp65 led to the infection of a population of acinar cells
      within the pancreas, the activation of NF-kappaB, the expression of NF-kappaB
      target genes, and an inflammatory response. Administration of Adp65 increased the
      infiltration of neutrophils to the pancreas and lung and caused widespread damage
      to pancreatic acinar cells. In contrast, at the same titer, control adenovirus
      (AdGFP) had no effect on these parameters. The level of NF-kappaB activation and
      the severity of inflammation were reduced when an adenovirus bearing the
      inhibitory subunit IkappaB-alpha was coadministered with Adp65. CONCLUSIONS:
      Thus, activation of NF-kappaB within the pancreas was sufficient for the
      initiation of an inflammatory response in this model. These results help define
      the specific role of NF-kappaB activation in acute pancreatitis.

PMID- 11832460
TI  - Esophageal ulceration activates keratinocyte growth factor and its receptor in
      rats: implications for ulcer healing.
AB  - BACKGROUND & AIMS: Cellular and molecular mechanisms of esophageal ulcer healing
      remain unexplored. We studied the sequential cellular events and the expression
      of keratinocyte growth factor (KGF) and its receptor (KGF-R) during the healing
      of experimental esophageal ulcers. METHODS: Esophageal ulcers were produced in
      rats by local application of acetic acid. Studies included (1) ulcer size, (2)
      quantitative histology, and (3) KGF and KGF-R messenger RNA and protein
      expression by reverse-transcription polymerase chain reaction, Western blotting,
      and immunostaining. In separate groups, ulcer size and esophageal epithelial
      proliferation were evaluated after a single injection of recombinant human KGF (1
      mg/kg) around the ulcer. RESULTS: Ulcers were fully developed 3 days after
      induction, and 58% of ulcers were re-epithelialized by 9 days. At 3 days, in
      esophageal tissue bordering the ulcers, KGF messenger RNA and protein were
      increased by 191% and 151%, respectively, and KGF-R messenger RNA and protein
      were increased by 357% and 237%, respectively. KGF was expressed in stromal
      cells, whereas KGF-R was expressed in epithelial cells. At 6 days, epithelial
      proliferation at the ulcer margin was increased by 216%, and treatment with KGF
      further enhanced cell proliferation and accelerated ulcer healing. CONCLUSIONS:
      KGF is a likely mediator of esophageal epithelial proliferation and ulcer
      healing.

PMID- 11832461
TI  - Disruption of hedgehog signaling reveals a novel role in intestinal morphogenesis
      and intestinal-specific lipid metabolism in mice.
AB  - BACKGROUND & AIMS: The hedgehog (hh) signaling pathway has been shown to play
      crucial roles in the development of embryonic gut. However, its role in
      intestinal development and function beyond the embryonic stage is still
      undefined. METHODS: Expression of hh and its receptor, Patched, were examined by
      Western blot and X-gal staining. An anti-hh monoclonal antibody was administered
      into developing embryos or postnatal mice and histologic analyses were performed.
      Effects on lipid metabolism were examined by Oil Red O and Sudan III stainings,
      messenger RNA (mRNA) analysis, and electron microscopy. Serum apolipoprotein IV
      level, a marker for lipid absorption, was quantified by Western blot. RESULTS:
      Mice receiving anti-hh monoclonal antibody in utero or after birth exhibited
      progressive runting and died before weaning. Histology revealed
      hyperproliferation of intestinal crypt epithelial cells and disorganization of
      the villi with prominent vacuolation and accumulation of neutral lipid. Fecal fat
      microscopy revealed numerous large fat droplets. Intestinal mRNA abundance of 2
      candidate genes involved in lipid transport, mtp and apob, was unchanged,
      although serum levels of apolipoprotein A-IV were reduced. CONCLUSIONS: Abnormal
      villus structure, lipid-filled enterocytes, and fatty stools in anti-hh
      monoclonal antibody-treated mice indicate a novel role for hh signaling in
      intestinal morphogenesis and lipid transport in postnatal mice.

PMID- 11832463
TI  - Intestinal ischemia and peripheral gangrene in a patient with chronic renal
      failure.
AB  - Gastrointestinal complications are common in patients with renal failure and
      result in significant morbidity and mortality. Systemic calciphylaxis is an
      uncommon complication of renal failure, characterized by disseminated
      intravascular calcification and associated with progressive vascular compromise.
      We describe the case of a 63-year-old woman who presented with abdominal pain,
      elevated transaminases, and skin manifestations consistent with a vasculitic
      process. Hand films and skin biopsies showed extensive vascular calcification,
      and a computerized tomography scan confirmed colonic perforation and disseminated
      visceral vascular calcification. Histologic analysis of the resected skin and
      colonic tissues revealed extensive ischemic damage and mural calcification of
      medium to large vessels. Gastrointestinal involvement has been reported in only 3
      prior cases of calciphylaxis; consequently, gastroenterologists are often unaware
      of this disease entity and may fail to recognize it, even in patients with the
      classical presentation. Prompt diagnosis is crucial, as parathyroidectomy may
      result in clinical improvement in up to two thirds of patients who present with
      elevated parathyroid hormone levels.

PMID- 11832462
TI  - Selective modulation of PKC isozymes by inflammation in canine colonic circular
      muscle cells.
AB  - BACKGROUND & AIMS: Protein kinase C (PKC) is a key signaling molecule in
      excitation-contraction coupling in several types of smooth muscle cells. We
      investigated whether the attenuated contraction in inflamed colon cells is caused
      by alterations in the expression, distribution, and activation of specific PKC
      isozymes. METHODS: Kinase assays, immunofluorescence imaging, and Western
      immunoblotting were performed on single circular smooth muscle cells obtained
      from the normal dog colon as well as from colon with experimental colitis induced
      by mucosal exposure to ethanol and acetic acid, to determine the distribution,
      expression, and activation of PKC isozymes. RESULTS: Classical (alpha, beta, and
      gamma), novel (delta and epsilon), and the atypical PKC (iota, lambda, and zeta)
      isozymes were detected in colonic circular muscle cells. The expression of PKC
      alpha, beta, and epsilon isozymes was down-regulated, whereas that of PKC iota
      and lambda isozymes was up-regulated; other isozymes were not affected by
      inflammation. Acetylcholine (ACh) treatment translocated only the PKC alpha,
      beta, and epsilon isozymes from the cytosol to the membrane in normal cells; this
      translocation was absent in inflamed colon cells. Immunofluorescence imaging
      confirmed the translocation of PKC alpha from the cytosol to the membrane in
      response to ACh in normal cells. PKC inhibitors, chelerythrine, and myristoylated
      peptides to alpha, beta, and epsilon isozymes inhibited the contractile response
      to ACh in normal, but not in inflamed, cells. PKC iota and lambda did not
      participate in the contractile response to ACh. CONCLUSIONS: ACh-induced
      contraction is mediated by PKC alpha, beta, and epsilon isozymes in normal
      colonic circular muscle cells. Contractile dysfunction in inflamed colon cells
      is, in part, caused by decreased expression and impaired activation of specific
      PKC isozymes.

PMID- 11832464
TI  - Dominant negative action of an abnormal secretin receptor arising from mRNA
      missplicing in a gastrinoma.
AB  - BACKGROUND & AIMS: The provocative secretin-stimulation test has an important
      role in the diagnosis and management of gastrin-secreting neuroendocrine tumors.
      The aim of the present study was to explore the molecular basis for positive and
      false-negative secretin-stimulation test results in patients with these tumors.
      METHODS: One of the rare patients with this histologically proven tumor who had a
      normal serum gastrin level and a negative secretin-stimulation test result, and 2
      more typical patients with this syndrome were investigated using
      immunohistochemistry, reverse-transcription polymerase chain reaction, receptor
      binding, and signaling assays. RESULTS: We confirmed the molecular nature of the
      secretin receptor in the gastrinomas with a positive provocative test result and
      identified a novel mechanism for a false-negative result. Tumor expression of the
      class B G protein-coupled secretin receptor mediates a positive result. The false
      negative result was explained by messenger RNA missplicing, resulting in a
      receptor variant missing exon 3 that encodes residues 44-79 in the amino-terminal
      tail of the mature receptor. This variant with an in-frame deletion was shown to
      be synthesized and to traffic to the cell surface normally, where it could
      neither bind secretin nor mediate a secretin-stimulated adenosine 3',5'-cyclic
      monophosphate response. It was able to act as a dominant negative inhibitor of
      wild-type secretin receptor function. CONCLUSIONS: These data may explain some of
      the atypical presentations of this syndrome and provide important insights into
      basic mechanisms of disease.

PMID- 11832465
TI  - A review of activity indices and efficacy endpoints for clinical trials of
      medical therapy in adults with Crohn's disease.

PMID- 11832466
TI  - Biological actions and therapeutic potential of the glucagon-like peptides.
AB  - The glucagon-like peptides (GLP-1 and GLP-2) are proglucagon-derived peptides
      cosecreted from gut endocrine cells in response to nutrient ingestion. GLP-1 acts
      as an incretin to lower blood glucose via stimulation of insulin secretion from
      islet beta cells. GLP-1 also exerts actions independent of insulin secretion,
      including inhibition of gastric emptying and acid secretion, reduction in food
      ingestion and glucagon secretion, and stimulation of beta-cell proliferation.
      Administration of GLP-1 lowers blood glucose and reduces food intake in human
      subjects with type 2 diabetes. GLP-2 promotes nutrient absorption via expansion
      of the mucosal epithelium by stimulation of crypt cell proliferation and
      inhibition of apoptosis in the small intestine. GLP-2 also reduces epithelial
      permeability, and decreases meal-stimulated gastric acid secretion and
      gastrointestinal motility. Administration of GLP-2 in the setting of experimental
      intestinal injury is associated with reduced epithelial damage, decreased
      bacterial infection, and decreased mortality or gut injury in rodents with
      chemically induced enteritis, vascular-ischemia reperfusion injury, and dextran
      sulfate-induced colitis. GLP-2 also attenuates chemotherapy-induced mucositis via
      inhibition of drug-induced apoptosis in the small and large bowel. GLP-2 improves
      intestinal adaptation and nutrient absorption in rats after major small bowel
      resection, and in humans with short bowel syndrome. The actions of GLP-2 are
      mediated by a distinct GLP-2 receptor expressed on subsets of enteric nerves and
      enteroendocrine cells in the stomach and small and large intestine. The
      beneficial actions of GLP-1 and GLP-2 in preclinical and clinical studies of
      diabetes and intestinal disease, respectively, has fostered interest in the
      potential therapeutic use of these gut peptides. Nevertheless, the actions of the
      glucagon-like peptides are limited in duration by enzymatic inactivation via
      cleavage at the N-terminal penultimate alanine by dipeptidyl peptidase IV (DP
      IV). Hence, inhibitors of DP IV activity, or DP IV-resistant glucagon-like
      peptide analogues, may be alternative therapeutic approaches for treatment of
      human diseases.

PMID- 11832467
TI  - Water transport by epithelia of the digestive tract.

PMID- 11832468
TI  - Hereditary hemochromatosis and alcohol: a fibrogenic cocktail.

PMID- 11832469
TI  - HMG-CoA reductase inhibitors for the treatment of pancreatic cancer.

PMID- 11832470
TI  - Hepatitis C virus proteins: direct link to hepatic oxidative stress, steatosis,
      carcinogenesis and more.

PMID- 11832471
TI  - Optical biopsies, "bioendoscopy," and why the sky is blue: the coming revolution
      in gastrointestinal imaging.

PMID- 11832472
TI  - Air apparent: studies of gas and bloating in IBS.

PMID- 11832473
TI  - Whomsoever ignores the natural history of the hepatitis C virus is doomed to
      treat it.

PMID- 11832474
TI  - Expansion of criteria for liver transplantation in HCC: a slippery slope?

PMID- 11832475
TI  - Protein shakes.

PMID- 11832477
TI  - Folding of a de novo designed native-like four-helix bundle protein.
AB  - The folding of a model native-like dimeric four-helix bundle protein,
      (alpha(2))(2), was investigated using guanidine hydrochloride, hydrostatic
      pressure, and low temperature. Unfolding by guanidine hydrochloride followed by
      circular dichroism and intrinsic fluorescence spectroscopy revealed a highly
      cooperative transition between the native-like and unfolded states, with free
      energy of unfolding determined from CD data, DeltaG(unf) = 14.3 +/- 0.8 kcal/mol.
      However, CD and intrinsic fluorescence data were not superimposable, indicating
      the presence of an intermediate state during the folding transition. To stabilize
      the folding intermediate, we used hydrostatic pressure and low temperature. In
      both cases, dissociation of the dimeric native-like (alpha(2))(2) into folded
      monomers (alpha(2)) was observed. van't Hoff analysis of the low temperature
      experiments, assuming a two-state dimer 171-monomer transition, yielded a free
      energy of dissociation of (alpha(2))(2) of DeltaG(diss) = 11.4 +/- 0.4 kcal/mol,
      in good agreement with the free energy determined from pressure dissociation
      experiments (DeltaG(diss) = 10.5 +/- 0.1 kcal/mol). Binding of the hydrophobic
      fluorescent probe 4,4'-dianilino-1,1'-binaphthyl-5,5'-disulfonic acid (bis-ANS)
      to the pressure- and cold-dissociated states of (alpha(2))(2) indicated the
      existence of molten-globule monomers. In conclusion, we demonstrate that the
      folding pathway of (alpha(2))(2) can be described by a three-state transition
      including a monomeric molten globule-like state.

PMID- 11832478
TI  - Caspase-2 induces apoptosis by releasing proapoptotic proteins from mitochondria.
AB  - Caspase-2 is one of the earliest identified caspases, but the mechanism of
      caspase-2-induced apoptosis remains unknown. We show here that caspase-2 engages
      the mitochondria-dependent apoptotic pathway by inducing the release of
      cytochrome c (Cyt c) and other mitochondrial apoptogenic factors into the cell
      cytoplasm. In support of these observations we found that Bcl-2 and Bcl-xL can
      block caspase-2- and CRADD (caspase and RIP adaptor with death domain)-induced
      cell death. Unlike caspase-8, which can process all known caspase zymogens
      directly, caspase-2 is completely inactive toward other caspase zymogens.
      However, like caspase-8, physiological levels of purified caspase-2 can cleave
      cytosolic Bid protein, which in turn can trigger the release of Cyt c from
      isolated mitochondria. Interestingly, caspase-2 can also induce directly the
      release of Cyt c, AIF (apoptosis-inducing factor), and Smac (second mitochondria
      derived activator of caspases protein) from isolated mitochondria independent of
      Bid or other cytosolic factors. The caspase-2-released Cyt c is sufficient to
      activate the Apaf-caspase-9 apoptosome in vitro. In combination, our data suggest
      that caspase-2 is a direct effector of the mitochondrial apoptotic pathway.

PMID- 11832479
TI  - Truncation of NH2-terminal amino acid residues increases agonistic potency of
      leukotactin-1 on CC chemokine receptors 1 and 3.
AB  - Leukotactin-1 (Lkn-1) is a human CC chemokine that binds to both CC chemokine
      receptor 1 (CCR1) and CCR3. Structurally, Lkn-1 is distinct from other human CC
      chemokines in that it has long amino acid residues preceding the first cysteine
      at the NH(2) terminus, and contains two extra cysteines. NH(2)-terminal amino
      acids of Lkn-1 were deleted serially, and the effects of each deletion were
      investigated. In CCR1-expressing cells, serial deletion up to 20 amino acids
      (Delta20) did not change the calcium flux-inducing activity significantly.
      Deletion of 24 amino acids (Delta24), however, increased the agonistic potency
      approximately 100-fold. Deletion of 27 or 28 amino acids also increased the
      agonistic potency to the same level shown by Delta24. Deletion of 29 amino acids,
      however, abolished the agonistic activity almost completely showing that at least
      3 amino acid residues preceding the first cysteine at the NH(2) terminus are
      essential for the biological activity of Lkn-1. Loss of agonistic activity was
      due to impaired binding to CCR1. In CCR3-expressing cells, Delta24 was the only
      form of Lkn-1 mutants that revealed increased agonistic potency. Our results
      indicate that posttranslational modification is a potential mechanism for the
      regulation of biological activity of Lkn-1.

PMID- 11832480
TI  - Asymmetric photocross-linking pattern of restriction endonuclease EcoRII to the
      DNA recognition sequence.
AB  - The EcoRII homodimer engages two of its recognition sequences (5'-CCWGG)
      simultaneously and is therefore a type IIE restriction endonuclease. To identify
      the amino acids of EcoRII that interact specifically with the recognition
      sequence, we photocross-linked EcoRII with oligonucleotide substrates that
      contained only one recognition sequence for EcoRII. In this recognition sequence,
      we substituted either 5-iododeoxycytidine for each C or 5-iododeoxyuridine for A,
      G, or T. These iodo-pyrimidine bases were excited using a UV laser to result in
      covalent cross-linking products. The yield of EcoRII photocross-linked to the 5'
      C of the 5'-CCAGG strand of the recognition sequence was 45%. However, we could
      not photocross-link EcoRII to the 5'-C of the 5'-CCTGG strand. Thus, the contact
      of EcoRII to the bases of the recognition sequence appears to be asymmetric,
      unlike that expected for most type II restriction endonucleases. Tryptic
      digestion of free and of cross-linked EcoRII, followed by high performance liquid
      chromatography (HPLC) separation of the individual peptides and Edman
      degradation, identified amino acids 25-49 of EcoRII as the cross-linking peptide.
      Mutational analysis of the electron-rich amino acids His(36) and Tyr(41) of this
      peptide indicates that Tyr(41) is the amino acid involved in the cross-link and
      that it therefore contributes to specific DNA recognition by EcoRII.

PMID- 11832481
TI  - Rice alpha-amylase transcriptional enhancers direct multiple mode regulation of
      promoters in transgenic rice.
AB  - Expression of alpha-amylase genes in cereals is induced by both gibberellin (GA)
      and sugar starvation. In a transient expression assay, a 105-bp sugar response
      sequence (SRS) in the promoter of a sugar starvation highly inducible rice alpha
      amylase gene, alphaAmy3, was shown previously to confer sugar response and to
      enhance the activity of the rice Act1 promoter in rice protoplasts. A 230-bp SRS
      like sequence was also found in the promoter of another sugar starvation highly
      inducible rice alpha-amylase gene, alphaAmy8. The alphaAmy8 SRS contains a GA
      response sequence and was designated as alphaAmy8 SRS/GARS. In the present study,
      a transgenic approach was employed to characterize the function of the alpha
      amylase gene SRSs in rice. We found that the alphaAmy3 SRS significantly enhances
      the endogenous expression pattern of the Act1 promoter in various rice tissues
      throughout their developmental stages. By contrast, the alphaAmy8 SRS/GARS
      significantly enhances Act1 promoter activity only in embryos and endosperms of
      germinating rice seeds. A minimal promoter fused to the alphaAmy8 SRS/GARS is
      specifically active in rice embryo and endosperm and is subject to sugar
      repression and GA induction in rice embryos. This sugar repression was found to
      override GA induction of alphaAmy8 SRS/GARS activity. Our study demonstrates that
      the alpha-amylase transcriptional enhancers contain cis-acting elements capable
      of enhancing endogenous expression patterns or activating sugar-sensitive,
      hormone-responsive, tissue-specific, and developmental stage-dependent expression
      of promoters in transgenic rice. These enhancers may facilitate the design of
      highly active and tightly regulated composite promoters for monocot
      transformation and gene expression. Our study also reveals the existence of cross
      talk between the sugar and GA signaling pathways in cereals and provides a system
      for analyzing the underlying molecular mechanisms involved.

PMID- 11832482
TI  - In vitro (CTG)*(CAG) expansions and deletions by human cell extracts.
AB  - The mechanism of disease-associated (CTG)*(CAG) expansion may involve DNA
      replication slippage, replication direction, Okazaki fragment processing,
      recombination, or repair. A length-dependent bias for expansions is observed in
      humans affected by a trinucleotide repeat-associated disease. We developed an
      assay to test the effect of replication direction on (CTG)*(CAG) instabilities
      incurred during in vitro (SV40) DNA replication mediated by human cell extracts.
      This system recapitulates the bias for expansions observed in humans. Replication
      by HeLa cell extracts generated expansions and deletions that depended upon
      repeat tract length and the direction of replication. Templates with 79 repeats
      yielded predominantly expansions (CAG as lagging strand template) or
      predominantly deletions (CTG as lagging strand template). Templates containing 17
      repeats were stable. Thus, replication direction determined the type of mutation.
      These results provide new insights into the orientation of replication effect
      upon repeat stability. This system will be useful in determining the contribution
      of specific human proteins to (CTG)*(CAG) expansions.

PMID- 11832483
TI  - In vitro strand exchange promoted by the herpes simplex virus type-1 single
      strand DNA-binding protein (ICP8) and DNA helicase-primase.
AB  - The genome of herpes simplex virus type-1 undergoes a high frequency of
      homologous recombination in the absence of a virus-encoded RecA-type protein. We
      hypothesized that viral homologous recombination is mediated by the combined
      action of the viral single strand DNA-binding protein (ICP8) and helicase
      primase. Our results show that ICP8 catalyzes the formation of recombination
      intermediates (joint molecules) between circular single-stranded acceptor and
      linear duplex donor DNA. Joint molecules formed by invasion of a 3'-terminal
      strand displaces the non-complementary 5'-terminal strand, thereby creating a
      loading site for the helicase-primase. Helicase-primase acts on these joint
      molecules to promote ATP-dependent branch migration. Finally, we have
      reconstituted strand exchange by the synchronous action of ICP8 and helicase
      primase. Based on these data, we present a recombination mechanism for a
      eukaryotic DNA virus in which a single strand DNA-binding protein and helicase
      cooperate to promote homologous pairing and branch migration.

PMID- 11832484
TI  - Kaposi's sarcoma-associated herpesvirus K8 exon 3 contains three 5'-splice sites
      and harbors a K8.1 transcription start site.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) K8 and K8.1 open reading frames
      are juxtaposed and span from nucleotide (nt) 74850 to 76695 of the virus genome.
      A K8 pre-mRNA overlaps the entire K8.1 coding region, and alternative splicing of
      KSHV K8 and K8.1 pre-mRNAs each produces three isoforms (alpha, beta, and gamma)
      of the mRNAs. We have mapped the 5' end of the K8.1 RNA in butyrate-induced KSHV
      positive JSC-1 cells to nt 75901 in the KSHV genome and have shown that exon 3 of
      the K8 pre-mRNA in JSC-1 cells covers most part of the intron 3 defined
      previously and has three 5'-splice sites (ss), respectively, at nt 75838, 76155,
      and 76338. Selection of the nt 75838 5'-ss dictates the K8 mRNA production and
      overwhelms the RNA processing. Alternative selection of other two 5'-ss is
      feasible and leads to production of two additional bicistronic mRNAs,
      K8/K8.1alpha and -beta. However, the novel bicistronic K8/K8.1 mRNAs translated a
      little K8 and no detectable K8.1 proteins in 293 cells. Data suggest that
      production of the K8/K8.1 mRNAs may be an essential way to control K8 mRNAs,
      especially K8alpha, to a threshold at RNA processing level.

PMID- 11832485
TI  - Alternative splicing of the IIICS domain in fibronectin governs the role of the
      heparin II domain in fibrillogenesis and cell spreading.
AB  - The Heparin (Hep) II-binding domain of fibronectin regulates the formation of
      focal adhesions and actin stress fibers and hence plays an important role in cell
      spreading, migration, and fibronectin fibrillogenesis. Using human skin
      fibroblast cultures, we demonstrate that alternative splicing of the neighboring
      IIICS domain may regulate the activities of the Hep II domain in cell spreading
      and fibronectin fibrillogenesis. Recombinant Hep II domains, adjacent to either
      the IIICS domain or the H89 splice variant that contains the amino-terminal
      sequence of the IIICS domain, blocked fibronectin fibrillogenesis and required
      sulfated proteoglycans to mediate cell spreading. If the Hep II domain was
      adjacent to either the H0 or H95 splice variants, which both lack the amino
      terminus of the IIICS domain, fibrillogenesis was not inhibited and cell
      spreading was independent of a sulfated proteoglycan-mediated mechanism. The
      effect of the splice variants on the Hep II domain could be mimicked using a Hep
      II domain that contained only 6 amino acids from the III(15) repeat or 10 amino
      acids from the IIICS domain suggesting that sequences proximal to the III(14)
      repeat determined the role of the Hep II domain in these processes. We propose
      that alternative splicing of the IIICS domain modulates interactions between
      heparan sulfate proteoglycans and the Hep II domain and that this serves as a
      mechanism to control the biological activities of fibronectin.

PMID- 11832486
TI  - A zinc-finger protein, PLAGL2, induces the expression of a proapoptotic protein
      Nip3, leading to cellular apoptosis.
AB  - Pleomorphic adenomas gene-like 2 (PLAGL2) protein containing seven C(2)H(2) zinc
      finger motifs exhibits DNA binding and transcriptional activation activity and is
      expressed in response to hypoxia or iron deficiency. To identify the target genes
      of PLAGL2, we transfected mouse PLAGL2 cDNA into Balb/c3T3 fibroblasts and
      neuroblastoma Neuro2a cells. Both cells were induced to undergo apoptosis by the
      expression of PLAGL2 as judged by assays of TUNEL (terminal
      deoxynucleotidyltransferase-mediated dUTP nick end-labeling), DNA fragmentation,
      propidium iodide staining, and the binding of annexin V to the cell surface. The
      treatment of the cells with an iron chelator, desferrioxamine, resulted in the
      induction of apoptosis with a concomitant accumulation of PLAGL2 in the nucleus.
      The expression of PLAGL2 in Balb/c3T3 cells led to the mRNA expression of a
      proapoptotic factor, Nip3, which can dimerize with Bcl-2. Nip3 mRNA was also
      induced in desferrioxamine-treated cells. Furthermore, the Nip3 promoter
      containing a hypoxia-responsive element was activated by PLAGL2, independent of
      hypoxia-inducible factor-1 (HIF-1). The transfection of antisense oligonucleotide
      to mouse Nip3 mRNA into PLAGL2-expressing cells led to a decrease in apoptotic
      cells compared with sense oligonucleotide-transfected cells. Despite the
      activation of DNA-HIF-1 binding activity under hypoxic conditions, neither an
      accumulation of HIF-1 alpha nor the activation of HIF-1 was observed following
      the expression of PLAGL2. These results indicate that PLAGL2 is located
      downstream of HIF-1 and suggest that PLAGL2 functions as a tumor suppressor in
      association with HIF-1.

PMID- 11832487
TI  - Glutaredoxin-dependent peroxiredoxin from poplar: protein-protein interaction and
      catalytic mechanism.
AB  - Recently, a poplar phloem peroxiredoxin (Prx) was found to accept both
      glutaredoxin (Grx) and thioredoxin (Trx) as proton donors. To investigate the
      catalytic mechanism of the Grx-dependent reduction of hydroperoxides catalyzed by
      Prx, a series of cysteinic mutants was constructed. Mutation of the most N
      terminal conserved cysteine of Prx (Cys-51) demonstrates that it is the catalytic
      one. The second cysteine (Cys-76) is not essential for peroxiredoxin activity
      because the C76A mutant retained approximately 25% of the wild type Prx activity.
      Only one cysteine of the Grx active site (Cys-27) is essential for peroxiredoxin
      catalysis, indicating that Grx can act in this reaction either via a dithiol or a
      monothiol pathway. The creation of covalent heterodimers between Prx and Grx
      mutants confirms that Prx Cys-51 and Grx Cys-27 are the two residues involved in
      the catalytic mechanism. The integration of a third cysteine in position 152 of
      the Prx, making it similar in sequence to the Trx-dependent human Prx V, resulted
      in a protein that had no detectable activity with Grx but kept activity with Trx.
      Based on these experimental results, a catalytic mechanism is proposed to explain
      the Grx- and Trx-dependent activities of poplar Prx.

PMID- 11832488
TI  - Demonstration of a novel gene DEXT3 of Drosophila melanogaster as the essential N
      acetylglucosamine transferase in the heparan sulfate biosynthesis: chain
      initiation and elongation.
AB  - Hereditary multiple exostoses gene (EXT) family members encode
      glycosyltransferases required for heparan sulfate (HS) biosynthesis in humans as
      well as in Drosophila. In the present study, we identified a novel Drosophila EXT
      protein with a type II transmembrane topology and demonstrated its
      glycosyltransferase activities. The truncated soluble form of this new homolog
      designated DEXT3 transferred N-acetylglucosamine (GlcNAc) through an alpha1,4
      linkage not only to N-acetylheparosan oligosaccharides that represent growing HS
      chains (alpha-GlcNAc transferase II activity) but also to GlcUAbeta1-3Galbeta1-O
      C(2)H(4)NHCbz, a synthetic substrate for alpha-GlcNAc transferase I that
      determines and initiates HS biosynthesis. The results suggest that DEXT3 is the
      ortholog of human EXTL3 and Caenorhabditis elegans rib-2. Semiquantitative
      reverse transcriptase-PCR analysis revealed ubiquitous expression of the DEXT3
      mRNA. Based on the findings of the present study and those of a recent study
      where a fly mutant, deficient in the botv gene identical to DEXT3, affected HS
      proteoglycan-mediated developmental signalings, it is suggested that DEXT3 with
      the revealed glycosyltransferase activities is critically involved in HS
      formation in Drosophila. These results suggest the essential roles of DEXT3, its
      human ortholog EXTL3, and the C. elegans ortholog rib-2 in the biosynthesis of
      heparan sulfate and heparin, if present, in the respective organisms.

PMID- 11832490
TI  - Membrane potential-controlled inhibition of cytochrome c oxidase by zinc.
AB  - Like many voltage-sensitive ion pumps, cytochrome c oxidase is inhibited by zinc.
      Binding of zinc to the outside surface of Rhodobacter sphaeroides cytochrome c
      oxidase inhibits the enzyme with a K(I) of < or = 5 microm when the enzyme is
      reconstituted into phospholipid vesicles in the presence of a membrane potential.
      In the absence of a membrane potential and a pH gradient, millimolar
      concentrations of zinc are required to inhibit. This differential inhibition
      causes a dramatic increase in the respiratory control ratio from 6 to 40 for wild
      type oxidase. The external zinc inhibition is removed by EDTA and is not
      competitive with cytochrome c binding but is competitive with protons. Only
      Cd(2+) of the many metals tested (Mg(2+), Mn(2+), Ca(2+), Ba(2+), Li(2+), Cs(2+),
      Hg(2+), Ni(2+), Co(2+), Cu(2+) Tb(3+), Tm(3+)) showed inhibitory effects similar
      to Zn(2+). Proton pumping is slower and less efficient with zinc. The results
      suggest that zinc inhibits proton movement through a proton exit path, which can
      allow proton back-leak at high membrane potentials. The physiological and
      mechanistic significance of proton movement in the exit pathway and its blockage
      by zinc is discussed in terms of regulation of the efficiency of energy
      transduction.

PMID- 11832489
TI  - NADPH oxidase is involved in prostaglandin F2alpha-induced hypertrophy of
      vascular smooth muscle cells: induction of NOX1 by PGF2alpha.
AB  - Prostaglandin (PG) F(2alpha), one of the primary prostanoids generated in
      vascular tissue, is known to cause hypertrophy in vascular smooth muscle cells.
      To clarify the molecular mechanisms underlying PGF(2alpha)-induced hypertrophy,
      the involvement of reactive oxygen species was examined in a rat vascular smooth
      muscle cell line, A7r5. PGF(2alpha) and (+)-fluprostenol, a selective agonist of
      the PGF receptor, significantly increased intracellular O(2)(-) in A7r5. The
      PGF(2alpha)-induced O(2)(-) increase was suppressed by diphenyleneiodonium (DPI),
      an inhibitor of NADPH oxidase that has been reported to be the major source of
      O(2)(-) in vascular cells. The augmented synthesis of the protein induced by
      PGF(2alpha) or (+)-fluprostenol was suppressed in the presence of DPI. In
      PGF(2alpha) or (+)-fluprostenol-treated cells, a dose-dependent increase in the
      expression of NOX1, a homolog of the catalytic subunit of the phagocyte NADPH
      oxidase gp91(phox), was demonstrated by Northern blot analysis. Finally,
      depletion of NOX1 mRNA in the cells transfected with ribozymes targeted for three
      independent cleavage sites on the mRNA sequence significantly reduced the
      PGF(2alpha)-induced increase in protein synthesis. Taken together, these results
      suggest that hypertrophy of vascular smooth muscle cells caused by PGF(2alpha) is
      mediated by NOX1 induction and the resultant overproduction of O(2)(-) by NADPH
      oxidase.

PMID- 11832491
TI  - Expression analysis and subcellular distribution of the two G-protein regulators
      AGS3 and LGN indicate distinct functionality. Localization of LGN to the midbody
      during cytokinesis.
AB  - Activator of G-protein signaling 3 (AGS3) and LGN have a similar domain structure
      and contain four G-protein regulatory motifs that serve as anchors for the
      binding of the GDP-bound conformation of specific G-protein alpha subunits. As an
      initial approach to define further the different functional roles of AGS3 and
      LGN, we determined their expression profile and subcellular distribution. AGS3-
      and LGN-specific antisera indicated a widespread tissue distribution of LGN,
      whereas AGS3 is primarily enriched in brain. Brain punch biopsies of 13 discrete
      brain regions indicated that both AGS3 and LGN are expressed in all areas tested
      but are differentially regulated during development. LGN is expressed in
      neuronal, astroglial, and microglial cultures, whereas AGS3 expression is
      restricted to neurons. In primary neuronal cultures as well as in dividing
      cultures of PC12 cells, immunocytochemistry indicated distinct subcellular
      locations of AGS3 and LGN. The subcellular locations of the two proteins were
      differentially regulated by external stimuli and the cell cycle. In PC12 and COS7
      cells, LGN moves from the nucleus to the midbody structure separating daughter
      cells during the later stages of mitosis, suggesting a role for G-proteins in
      cytokinesis. Thus, although AGS3 and LGN share a similar overall motif structure
      and both bind G-proteins, nature has endowed these proteins with different
      regulatory elements that allow functional diversity by virtue of tissue-specific
      expression and subcellular positioning.

PMID- 11832493
TI  - A dynamic RecA filament permits DNA polymerase-catalyzed extension of the
      invading strand in recombination intermediates.
AB  - Recombination-dependent replication is an essential housekeeping function in
      prokaryotes and eukaryotes, serving, for example, to restart DNA replication
      after the repair of a double-strand break. Little is known about the interplay
      between the recombination and replication machinery when recombination
      intermediates are used as substrates for DNA replication. We show here that
      recombination intermediates formed between linear duplex and supercoiled plasmid
      DNAs are substrates for a generalized strand displacement DNA synthesis reaction
      in which the 3'-OH of the invading strand in the recombination intermediate is
      used as a primer. DNA synthesis is driven by negative superhelicity and is
      inhibited if disassembly of the RecA filament is prevented. Thus, assembly and
      disassembly of RecA filaments in the same direction facilitates filament
      clearance from the 3'-end of the invading strand, allowing DNA synthesis to occur
      from recombination intermediates.

PMID- 11832492
TI  - Differential mitogenic effects of single chain hepatocyte growth factor
      (HGF)/scatter factor and HGF/NK1 following cleavage by factor Xa.
AB  - Hepatocyte growth factor/scatter factor (HGF/SF) is a multifunctional cytokine
      that is involved in many normal as well as pathological conditions. HGF/NK1, a
      splice variant of HGF/SF, has been reported to have either antagonistic or
      agonistic effects with regard to c-Met signaling depending on the cell type. In
      these experiments, we have determined that HGF/NK1 is a potent mitogen for rat
      hepatocytes in culture. Furthermore, we have found that coagulation factor Xa
      (fXa) is capable of cleaving HGF/NK1 and single chain HGF/SF (scHGF/SF). The
      products resulting from cleavage of HGF/NK1 or scHGF/SF by fXa appear as single
      bands under non-reducing conditions. The reaction products from the digestion of
      HGF/NK1 by fXa were separated under reducing conditions, and the cleavage site,
      as determined by N-terminal sequencing, was located C-terminal to arginine 134.
      Previous work established that the heparin-binding domain for HGF/SF is located
      in the N domain of HGF/SF. Additionally, the dimerization of the HGF/SF receptor
      (c-Met) by the ligand HGF/NK1 is facilitated by heparin and related sulfonated
      sugars on the cell surface, whereas heparin is not required for HGF/SF-mediated
      dimerization. Cleavage of single chain HGF/SF or HGF/NK1 by factor Xa does not
      alter the affinity of the respective molecules for heparin, but it did variably
      affect the associated mitogenic activity of these factors. The associated
      mitogenic activity of HGF/NK1 was reduced by more than 90%, whereas the mitogenic
      activity of scHGF/SF was unaffected. This suggests mandatory maintenance of a
      steric interaction of the N domain and the first kringle domain for HGF/NK1 to
      act as an agonist for rat hepatocyte growth but is not required by full-length
      HGF/SF.

PMID- 11832494
TI  - Different effects on human topoisomerase I by minor groove and intercalated
      deoxyguanosine adducts derived from two polycyclic aromatic hydrocarbon diol
      epoxides at or near a normal cleavage site.
AB  - Topoisomerase I (top1) relieves supercoiling in DNA by forming transient covalent
      cleavage complexes. These cleavage complexes can accumulate in the presence of
      damaged DNA or anticancer drugs that either intercalate or lie in the minor
      groove. Recently we reported that covalent diol epoxide (DE) adducts of
      benzo[a]pyrene (BaP) at the exocyclic amino group of G(+1) block cleavage at a
      preferred cleavage site ( approximately CTT-G(+1)G(+2)A approximately ) and cause
      accumulation of cleavage products at remote sites. In the present study, we have
      found that the 10S G(+2) adduct of BaP DE, which lies toward the scissile bond in
      the minor groove, blocks normal cleavage, whereas the 10R isomer, which orients
      away from this bond, allows normal cleavage but blocks religation. In contrast to
      BaP, the pair of benzo[c] phenanthrene (BcPh) DE adducts at G(+2), which
      intercalate from the minor groove either between G(+1)/G(+2) or between G(+2)/A,
      allow normal cleavage but block religation. Both intercalated BcPh DE adducts at
      G(+1) suppress normal cleavage, as do both groove bound BaP DE adducts at this
      position. These studies demonstrate that these DE adducts provide a novel set of
      tools to study DNA topoisomerases and emphasize the importance of contacts
      between the minor groove and top1's catalytic site.

PMID- 11832495
TI  - Synergistic induction of tumor antigens by Wnt-1 signaling and retinoic acid
      revealed by gene expression profiling.
AB  - Novel drug targets can be identified by differential analysis of RNA transcripts
      isolated from cancer cell lines and tissues. We have extended this approach by
      analyzing differences in gene expression resulting from the drug treatment of
      transformed and nontransformed cells. A mouse mammary epithelial cell line
      (C57MG), which conditionally expresses the Wnt-1 proto-oncogene, was left
      untreated or treated with retinoic acid in the presence or absence of Wnt-1
      expression. The experiment was performed in triplicate, and RNA extracted from
      the four samples was analyzed by hybridization to over 12,000 unique
      oligonucleotide probe sets. Reproducible alterations in gene expression that
      occurred in response to retinoic acid, Wnt-1, or retinoic acid plus Wnt-1
      relative to untreated cells were identified. Greater attention was given to genes
      encoding cell surface antigens that were selectively up-regulated by the
      combination of Wnt-1 and retinoic acid. These genes included the tumor necrosis
      factor family 4-1BB ligand, ephrin B1, stra6, autotaxin, and ISLR. Administration
      of retinoic acid to mice bearing tumors driven by activation of the Wnt-1/beta
      catenin pathway resulted in increased expression of stra6 in the tumors but not
      in normal tissue. In principal, the therapeutic index of antibodies directed
      against these antigens should be enhanced by co-administration of retinoic acid.

PMID- 11832496
TI  - Root colonization by Pseudomonas putida: love at first sight.

PMID- 11832497
TI  - New chlamydial lineages from freshwater samples.

PMID- 11832498
TI  - Phenotypic heterogeneity: differential stress resistance among individual cells
      of the yeast Saccharomyces cerevisiae.

PMID- 11832499
TI  - Brucella abortus strain 2308 produces brucebactin, a highly efficient catecholic
      siderophore.
AB  - Brucella abortus is known to produce 2,3-dihydroxybenzoate (2,3-DHBA) and to use
      this catechol as a siderophore to grow under iron-limited conditions. In this
      study a mutant (BAM41) is described that is deficient in siderophore production
      by insertion of Tn5 in the virulent B. abortus strain 2308. This mutant was
      unable to grow on iron-deprived medium and its growth could not be restored by
      addition of 2,3-DHBA. Production of catecholic compounds by both the Brucella
      mutant and parental strains under iron-deprivation conditions was assayed by TLC.
      Two catecholic substances were identified in the supernatant of the parental
      strain 2308. The faster migrating spot showed the same retention factor (R(f)) as
      that of purified 2,3-DHBA. The mutant BAM41 overproduced 2,3-DHBA, but failed to
      form the slower migrating catechol. This defect could only be complemented by the
      addition of the slow-migrating catechol from strain 2308. The genomic region
      containing Tn5 in BAM41 was cloned and the position of the transposon was
      determined by nucleotide sequencing. The sequence revealed that the insertion had
      occurred at a gene with homology to Escherichia coli entF, a locus involved in
      the late steps of the biosynthesis of the complex catecholic siderophore
      enterobactin. Intracellular survival and growth rates of the B. abortus wild-type
      and entF mutant strains in mouse-derived J774 macrophages were similar,
      indicating that production of this siderophore was not essential in this model of
      infection. It is concluded that B. abortus synthesizes a previously unknown and
      highly efficient catecholic siderophore, different from 2,3-DHBA, for which the
      name brucebactin is proposed.

PMID- 11832500
TI  - 'Streptomyces nanchangensis', a producer of the insecticidal polyether antibiotic
      nanchangmycin and the antiparasitic macrolide meilingmycin, contains multiple
      polyketide gene clusters.
AB  - Several independent gene clusters containing varying lengths of type I polyketide
      synthase genes were isolated from 'Streptomyces nanchangensis' NS3226, a producer
      of nanchangmycin and meilingmycin. The former is a polyether compound similar to
      dianemycin and the latter is a macrolide compound similar to milbemycin, which
      shares the same macrolide ring as avermectin but has different side groups.
      Clusters A-H spanned about 133, 132, 104, 174, 122, 54, 37 and 59 kb,
      respectively. Two systems were developed for functional analysis of the gene
      clusters by gene disruption or replacement. (1) Streptomyces phage phiC31 and its
      derived vectors can infect and lysogenize this strain. (2) pSET152, an
      Escherichia coli plasmid with phiC31 attP site, and pHZ1358, a Streptomyces
      Escherichia coli shuttle cosmid vector, both carrying oriT from RP4, can be
      mobilized from E. coli into NS3226 by conjugation. pHZ1358 was shown to be
      generally useful for generating mutant strains by gene disruption and replacement
      in NS3226 as well as in several other Streptomyces strains. A region in cluster A
      (approximately 133 kb) seemed to be involved in nanchangmycin production because
      replacement of several DNA fragments in this region by an apramycin resistance
      gene [aac3(IV)] gave rise to nanchangmycin non-producing mutants.

PMID- 11832501
TI  - Analysis of a C-methyltransferase gene (aviG1) involved in avilamycin
      biosynthesis in Streptomyces viridochromogenes Tu57 and complementation of a
      Saccharopolyspora erythraea eryBIII mutant by aviG1.
AB  - Streptomyces viridochromogenes Tu57 is the principal producer of avilamycin A.
      aviG1, a putative methyltransferase gene, was detected in the avilamycin
      biosynthetic gene cluster. To determine the function of aviG1, a targeted gene
      inactivation experiment was performed. The resulting chromosomal mutant, carrying
      an in-frame deletion in aviG1, was deficient in avilamycin production. aviG1 was
      used to complement an eryBIII mutant of the erythromycin A producer
      Saccharopolyspora erythraea [Gaisser, S., Bohm, G. A., Doumith, M., Raynal, M.
      C., Dhillon, N., Cortes, J. & Leadlay, P. F. (1998). Mol Gen Genet 258, 78-88].
      The presence of erythromycin A in the culture supernatant of the complemented
      mutant indicated that L-mycarose biosynthesis could be restored and that AviG1
      could take over the function of the C-methyltransferase EryBIII.

PMID- 11832502
TI  - Osmotic regulation of the Streptomyces lividans thiostrepton-inducible promoter,
      ptipA.
AB  - Transcriptional activation of the thiostrepton-inducible promoter, ptipA, in
      Streptomyces lividans is mediated by TipAL. This transcriptional activator
      belongs to the MerR/SoxR family that characteristically binds an operator
      sequence located between the -10 and -35 hexamers normally occupied by RNA
      polymerase. As for the Escherichia coli merT promoter, the ptipA hexamers are
      separated by a long 19 bp spacer and hence a topological transition of the DNA is
      likely to be a requisite for alignment with RNA polymerase. Growth conditions
      that could facilitate this conformational change were investigated using
      transcriptional fusions of ptipA with reporter genes. Adjustment of growth medium
      osmolarity led to increased and prolonged TipAL-dependent expression, both with
      and without the inducer, thiostrepton. These effects correlated with increases in
      negative DNA supercoiling. Moreover, an inability to induce the promoter with
      thiostrepton in strain TK64 was corrected by increasing the concentration of
      osmolyte, compensating for an apparent reduced level of negative DNA supercoiling
      in the strain. Prolonging the time of activation of tipA in the wild-type by
      manipulating growth conditions revealed that mycelial autolysis could be induced
      by thiostrepton in 4-d-old cultures.

PMID- 11832503
TI  - Streptomyces spp. contain class Ia and class II ribonucleotide reductases:
      expression analysis of the genes in vegetative growth.
AB  - Genes encoding two ribonucleotide reductases (RNRs) were identified in members of
      the genus Streptomyces. One gene, nrdJ, encoded an oligomeric protein comprising
      four identical subunits each with a molecular mass of approximately 108 kDa. The
      activity of this protein depended on the presence of 5'-deoxyadenosylcobalamine
      (coenzyme B12), establishing it as a class II RNR. The Streptomyces clavuligerus
      nrdJ gene was cloned, using internal peptide sequences from the purified protein,
      and was found to encode a polypeptide of 961 aa. Molecular phylogenetic analysis
      showed that the S. clavuligerus class II RNR shares significant similarity with
      most other bacterial and archaeal class II RNRs. Two other genes, nrdA and nrdB,
      were initially identified in the Streptomyces coelicolor genome database in
      unannotated ORFs as encoding a class Ia RNR. Southern analysis demonstrated that
      the nrdAB genes were present in different Streptomyces spp. The S. coelicolor
      nrdAB genes were cloned and expressed in Escherichia coli, and the recombinant
      proteins were shown to represent a class I RNR. It was shown, using quantitative
      real-time PCR, that the S. clavuligerus class Ia and class II RNR genes were
      differentially transcribed during vegetative growth. The copy number of the class
      II nrdJ transcripts was approximately constant throughout the exponential phase
      of vegetative growth (3-5x10(5) copies per 400 ng total RNA after reverse
      transcription). In contrast, the copy number of the class Ia nrdAB transcripts
      was some 10- to 20-fold less than that of nrdJ in the early-exponential growth
      phase (2.8x10(4) copies), and decreased markedly at the mid-exponential (4x10(3)
      copies) and late-exponential phases (1.1x10(3) copies) of growth. A possible role
      for the involvement of two RNRs during vegetative growth is discussed.

PMID- 11832504
TI  - Nuclease activities and cell death processes associated with the development of
      surface cultures of Streptomyces antibioticus ETH 7451.
AB  - The presence and significance of developmentally regulated nucleases in
      Streptomyces antibioticus ETH 7451 has been studied in relation to the lytic
      processes occurring during differentiation. The cell-death processes have been
      followed in surface cultures by a propidium iodide viability assay. This has
      allowed the visualization of dead (membrane-damaged, red fluorescent) and live
      (membrane-intact, green fluorescent) mycelium during development, and has
      facilitated the analysis of the role of nucleases in these processes. A parallel
      activity-gel analysis showed the appearance of 20-22 kDa, 34 kDa and 44 kDa
      nucleases, the latter appearing only when aerial mycelium is formed. The
      appearance of these nucleases shows a remarkable correlation with the death
      process of the mycelium during differentiation and with chromosomal DNA
      degradation. The 20-22 kDa enzymes are possibly related to the lytic phenomena
      taking place in the vegetative substrate mycelium before the emergence of the
      reproductive aerial mycelium, whereas the function of the 44 kDa nuclease seems
      to be related to the sporulation step. The 20-22 kDa nucleases require Ca2+ for
      activity and are inhibited by Zn2+. The nucleases are loosely bound to the cell
      wall from where they can be liberated by simple washing. Conceivably, these
      enzymes work together and co-ordinate to achieve an efficient hydrolysis of DNA
      from dying cells. The results show that the biochemical reactions related with
      the lytic DNA degradation during the programmed cell death are notably conserved
      in Streptomyces. Some of the features of the process and the biochemical
      characteristics of the enzymes involved are analogous to those taking place
      during the DNA fragmentation processes in eukaryotic apoptotic cells.

PMID- 11832505
TI  - Kinetics of binding, uptake and degradation of live fluorescent (DsRed) bacteria
      by Dictyostelium discoideum.
AB  - The kinetics of binding, uptake and degradation of bacteria by vegetative
      Dictyostelium amoeba using Escherichia coli expressing the recombinant
      fluorescent protein DsRed have been characterized. There are significant
      advantages to using DsRed-expressing bacteria for phagocytosis assays. Stable
      expression of the fluorescent protein, DsRed, provides living bacteria with a
      bright internal fluorescent signal that is degradable in the phagolysosomal
      pathway. Unlike assays with chemically labelled bacteria or latex beads, the
      bacteria are alive and possess a natural, unaltered external surface for receptor
      interaction. Dictyostelium cells rapidly bind and phagocytose DsRed bacteria.
      Pulse-chase experiments show that the signal derived from DsRed is degraded with
      a half-life of approximately 45 min. To distinguish internalized bacteria from
      those bound to the surface, an assay was developed in which sodium azide was used
      to release surface-bound particles. Surprisingly, surface particle release
      appears to be independent of myosin II function. Using this assay it was shown
      that the uptake of bacteria into cells is extremely rapid. After 1 min
      incubation, 20% of the signal is derived from internalized bacteria. The
      proportion of the signal from internalized bacteria increases gradually and
      reaches 50% at steady state. This assay will be useful in investigations of the
      molecular machinery of phagocytosis and post-internalization vesicle trafficking.

PMID- 11832506
TI  - Physical and genetic map of the Lactobacillus sakei 23K chromosome.
AB  - The Lactobacillus sakei 23K chromosome was analysed by pulsed-field gel
      electrophoresis after digestion with the restriction enzymes AscI, NotI and SfiI.
      The chromosome size was estimated to be 1845+/-80 kb. The use of I-CeuI, specific
      for rrn genes encoding 23S rRNAs, showed that seven rrn loci were present, on 40%
      of the chromosome. The seven rrn clusters were mapped and their orientation was
      determined, allowing the position of the replication origin to be estimated.
      Partial I-CeuI digestions were used to construct a backbone and the different
      restriction fragments obtained with AscI, NotI and SfiI were assembled to a
      physical map by Southern hybridization. Eleven L. sakei gene clusters previously
      identified were mapped, as well as 25 new loci located randomly on the chromosome
      and 11 regions flanking the rrn gene clusters. A total of 47 clusters were thus
      mapped on L. sakei chromosome. The new loci were sequenced, allowing the
      identification of 73 complete or incomplete coding sequences. Among these 73 new
      genes of L. sakei, the function of 36 could be deduced from their similarity to
      known genes described in databases. However, 10 genes had no homologues, 10
      encoded proteins similar to proteins of unknown function and 17 were similar to
      hypothetical proteins.

PMID- 11832507
TI  - A high-molecular-mass cell-surface protein from Lactobacillus reuteri 1063
      adheres to mucus components.
AB  - A gene from Lactobacillus reuteri 1063 encoding a cell-surface protein,
      designated Mub, that adheres to mucus components in vitro has been cloned and
      sequenced. The deduced amino acid sequence of Mub (358 kDa) shows the presence of
      14 approximately 200 aa repeats and features typical for other cell-surface
      proteins of Gram-positive bacteria. Fusion proteins consisting of different
      repeats of Mub and the maltose-binding protein (MBP) were produced. These
      proteins adhered to pig mucus components, with molecular masses ranging from <0.1
      to >2 MDa, to pig gastric mucin and to hen intestinal mucus. The binding of Mub
      to mucus components occurred in the pH range 3-7.4, with maximum binding at pH 4
      5 and could be partly inhibited by the glycoprotein fetuin. Affinity-purified
      antibodies against recombinant Mub were used in immunofluorescence microscopy to
      demonstrate the presence of Mub on the cell surface of strain 1063. By using the
      antibodies in a Western blot analysis, Mub could also be detected in the growth
      medium. The results implicate Mub as a cell-surface protein that is involved in
      Lactobacillus interactions with mucin and in colonization of the digestive tract.

PMID- 11832508
TI  - Phage-display antibody detection of Chlamydia trachomatis-associated antigens.
AB  - A phage-displayed human single-chain Fv antibody library (6.7x10(9) members) was
      used to select probes specific to components associated with the surface of
      Chlamydia trachomatis elementary bodies (EBs). Each of 15 antibodies was
      characterized by ELISA, dot-blot, immunoblot and immunocytochemistry, resulting
      in the identification of several new chlamydial components associated with the
      surface of EBs. In addition, six antibodies were specific for host-cell
      components associated with the surface of EBs. While phage display has been used
      effectively to produce specific antibodies for purified components, these data
      show that this technology is suitable for selection of specific probes from
      complex antigens such as the surface of a microbial pathogen.

PMID- 11832509
TI  - Genotyping of axenic and non-axenic isolates of the genus Prochlorococcus and the
      OMF-'Synechococcus' clade by size, sequence analysis or RFLP of the Internal
      Transcribed Spacer of the ribosomal operon.
AB  - PCR amplicons of the Internal Transcribed Spacer (ITS) of the rrn operon of three
      axenic OMF (oceanic, marine and freshwater) strains of 'Synechococcus' (WH7803,
      PCC 7001 and PCC 6307, respectively) differ greatly in length from that of the
      axenic Prochlorococcus marinus subsp. pastoris PCC 9511(T), although these four
      cyanobacteria cluster relatively closely in phylogenetic trees inferred from 16S
      rRNA gene sequences. The ITSs of three strains (PCC 9511(T), PCC 6307 and PCC
      7001) were sequenced and compared with those available for strains
      Prochlorococcus MED4 (CCMP 1378) and MIT9313 from genome sequencing projects. In
      spite of large differences in length, sequence and mean DNA base composition,
      conserved domains important for transcriptional antitermination and folding of
      the rRNA transcripts were identified in all ITSs. A new group-specific primer
      permitted ITS amplification even with non-axenic isolates of Prochlorococcus and
      one OMF-'Synechococcus' strain. Prochlorococcus isolates of the high-light
      adapted clade (HL) differed from representatives of the low-light-adapted clade
      (LL) by the length of their ITS. Restriction fragment length polymorphism (RFLP)
      of the ITS amplicons revealed three subclusters among the HL strains. Size,
      sequence data and RFLP of the ITS amplicons will therefore be valuable markers
      for the identification of different Prochlorococcus genotypes and for their
      discrimination from other cyanobacterial relatives with which they often co-exist
      in oceanic ecosystems.

PMID- 11832510
TI  - Fusobacterium nucleatum supports the growth of Porphyromonas gingivalis in
      oxygenated and carbon-dioxide-depleted environments.
AB  - The authors compared the differences in tolerance to oxygen of the anaerobic
      periodontopathic bacteria Fusobacterium nucleatum and Porphyromonas gingivalis,
      and explored the possibility that F. nucleatum might be able to support the
      growth of P. gingivalis in aerated and CO2-depleted environments. Both micro
      organisms were grown as monocultures and in co-culture in the presence and
      absence of CO2 and under different aerated conditions using a continuous culture
      system. At steady state, viable counts were performed and the activities of the
      enzymes superoxide dismutase and NADH oxidase/peroxidase were assayed in P.
      gingivalis. In co-culture, F. nucleatum was able to support the growth of P.
      gingivalis in aerated and CO2-depleted environments in which P. gingivalis, as a
      monoculture, was not able to survive. F. nucleatum not only appeared to have a
      much higher tolerance to oxygen than P. gingivalis, but a significant increase in
      its numbers occurred under moderately oxygenated conditions. F. nucleatum might
      have an additional indirect role in dental plaque maturation, contributing to the
      reducing conditions necessary for the survival of P. gingivalis and possibly
      other anaerobes less tolerant to oxygen. Additionally, F. nucleatum is able to
      generate a capnophilic environment essential for the growth of P. gingivalis.

PMID- 11832511
TI  - A novel paralogous gene family involved in phase-variable flagella-mediated
      motility in Campylobacter jejuni.
AB  - Flagella-mediated motility is recognized to be one of the major factors
      contributing to virulence in Campylobacter jejuni. Motility of this bacterium is
      known to be phase variable, although the mechanism of such variation remains
      unknown. C. jejuni genome sequencing revealed a number of genes prone to phase
      variation via a slipped-strand mispairing mechanism. Many of these genes are
      hypothetical and are clustered in the regions involved in formation of three
      major cell surface structures: capsular polysaccharide, lipooligosaccharide and
      flagella. Among the genes of unknown function, the flagellar biosynthesis and
      modification region contains seven hypothetical paralogous genes designated as
      the motility accessory factor (maf) family. Remarkably, two of these genes (maf1
      and maf4) were found to be identical and both contain homopolymeric G tracts.
      Using insertional mutagenesis it was demonstrated that one of the genes, maf5, is
      involved in formation of flagella. Phase variation of the maf1 gene via slipped
      strand mispairing partially restored motility of the maf5 mutant. The maf family
      represents a new class of bacterial genes related to flagellar biosynthesis and
      phase variation. Reversible expression of flagella may be advantageous for the
      adaptation of C. jejunito the varied in vivo and ex vivo environments encountered
      during its life cycle, as well in evasion of the host immune response.

PMID- 11832512
TI  - rDNA analyses of planktonic heterocystous cyanobacteria, including members of the
      genera Anabaenopsis and Cyanospira.
AB  - The taxonomic coherence and phylogenetic relationships of 11 planktonic
      heterocystous cyanobacterial isolates were examined by investigating two areas of
      the rRNA operon, the 16S rRNA gene (rrnS) and the internal transcribed spacer
      (ITS) located between the 16S rRNA and 23S rRNA genes. The rrnS sequences were
      determined for five strains, including representatives of Anabaena flos-aquae,
      Aphanizomenon flos-aquae, Nodularia sp. and two alkaliphilic planktonic members
      of the genera Anabaenopsis and Cyanospira, whose phylogenetic position was
      previously unknown. Comparison of the data with those previously published for
      individual groups of planktonic heterocystous cyanobacteria showed that, with the
      exception of members assigned to the genus Cylindrospermopsis, all the planktonic
      strains form a distinct subclade within the monophyletic clade of heterocystous
      cyanobacteria. Within this subclade five different phylogenetic clusters were
      distinguished. The phylogenetic groupings of Anabaena and Aphanizomenon strains
      within three of these clusters were not always consistent with their generic or
      specific assignments based on classical morphological definitions, and the high
      degree of sequence similarity between strains of Anabaenopsis and Cyanospira
      suggests that they may be assignable to a single genus. Ribotyping and additional
      studies performed on PCR amplicons of the 16S rDNA or the ITS for the 11
      planktonic heterocystous strains demonstrated that they all contain multiple rrn
      operons and ITS regions of variable size. Finally, evidence is provided for intra
      genomic sequence heterogeneity of the 16S rRNA genes within most of the
      individual isolates.

PMID- 11832513
TI  - In vitro reconstructed human epithelia reveal contributions of Candida albicans
      EFG1 and CPH1 to adhesion and invasion.
AB  - The individual and synergistic contributions of two transcription factors, EFG1
      and CPH1, have been characterized with regard to adhesion to, and invasion of,
      human epithelia by Candida albicans. For this purpose two in vitro reconstructed
      tissue models were developed. A multi-layered model of human epidermis was used
      to simulate superficial infections of the skin, whereas a reconstructed human
      intestinal model was used to mimic the first steps of systemic infections. It was
      shown that C. albicans deleted for both transcription factors CPH1 and EFG1, in
      contrast to the congenic clinical isolate Sc5314, was neither able to adhere to,
      nor to penetrate, either of the model systems. A strain deleted for EFG1 alone
      showed significant reduction in adhesion and was not able to penetrate through
      the stratum corneum. However, strains deleted for CPH1 showed phenotypes
      paralleling the phenotypes of the clinical isolate Sc5314. Using different types
      of multi-layered human tissues reconstructed in vitro the individual
      contributions of Efg1p and Cph1p to two important virulence factors of C.
      albicans, namely adhesion and invasion, could be defined.

PMID- 11832514
TI  - The metIC operon involved in methionine biosynthesis in Bacillus subtilis is
      controlled by transcription antitermination.
AB  - There are two major pathways for methionine biosynthesis in micro-organisms.
      Little is known about these pathways in Bacillus subtilis. The authors assigned a
      function to the metI (formerly yjcI) and metC (formerly yjcJ) genes of B.
      subtilis by complementing Escherichia coli metB and metC mutants, analysing the
      phenotype of B. subtilis metI and metC mutants, and carrying out enzyme activity
      assays. These genes encode polypeptides belonging to the cystathionine gamma
      synthase family of proteins. Interestingly, the MetI protein has both
      cystathionine gamma-synthase and O-acetylhomoserine thiolyase activities, whereas
      the MetC protein is a cystathionine beta-lyase. In B. subtilis, the
      transsulfuration and the thiolation pathways are functional in vivo. Due to its
      dual activity, the MetI protein participates in both pathways. The metI and metC
      genes form an operon, the expression of which is subject to sulfur-dependent
      regulation. When the sulfur source is sulfate or cysteine the transcription of
      this operon is high. Conversely, when the sulfur source is methionine its
      transcription is low. An S-box sequence, which is located upstream of the metI
      gene, is involved in the regulation of the metIC operon. Northern blot
      experiments demonstrated the existence of two transcripts: a small transcript
      corresponding to the premature transcription termination at the terminator
      present in the S-box and a large one corresponding to transcription of the
      complete metIC operon. When methionine levels were limiting, the amount of the
      full-length transcript increased. These results substantiate a model of
      regulation by transcription antitermination.

PMID- 11832515
TI  - Discrimination of Mycobacterium tuberculosis complex bacteria using novel VNTR
      PCR targets.
AB  - The lack of a convenient high-resolution strain-typing method has hampered the
      application of molecular epidemiology to the surveillance of bacteria of the
      Mycobacterium tuberculosis complex, particularly the monitoring of strains of
      Mycobacterium bovis. With the recent availability of genome sequences for strains
      of the M. tuberculosis complex, novel PCR-based M. tuberculosis-typing methods
      have been developed, which target the variable-number tandem repeats (VNTRs) of
      minisatellite-like mycobacterial interspersed repetitive units (MIRUs), or exact
      tandem repeats (ETRs). This paper describes the identification of seven VNTR loci
      in M. tuberculosis H37Rv, the copy number of which varies in other strains of the
      M. tuberculosis complex. Six of these VNTRs were applied to a panel of 100
      different M. bovis isolates, and their discrimination and correlation with
      spoligotyping and an established set of ETRs were assessed. The number of alleles
      varied from three to seven at the novel VNTR loci, which differed markedly in
      their discrimination index. There was positive correlation between spoligotyping,
      ETR- and VNTR-typing. VNTR-PCR discriminates well between M. bovis strains.
      Thirty-three allele profiles were identified by the novel VNTRs, 22 for the ETRs
      and 29 for spoligotyping. When VNTR- and ETR-typing results were combined, a
      total of 51 different profiles were identified. Digital nomenclature and
      databasing were intuitive. VNTRs were located both in intergenic regions and
      annotated ORFs, including PPE (novel glycine-asparigine-rich) proteins, a
      proposed source of antigenic variation, where VNTRs potentially code repeating
      amino acid motifs. VNTR-PCR is a valuable tool for strain typing and for the
      study of the global molecular epidemiology of the M. tuberculosis complex. The
      novel VNTR targets identified in this study should additionally increase the
      power of this approach.

PMID- 11832516
TI  - Signal-sequence-independent secretion of the staphylococcal nuclease in
      Mycobacterium smegmatis.
AB  - Staphylococcus aureus nuclease is a small, secreted protein which has been
      successfully used as a reporter system to identify exported products in
      Lactococcus lactis. Here, biochemical evidence is provided that the nuclease is
      exported by Mycobacterium smegmatis in the presence, but also in the absence of a
      signal sequence, and thus probably independently of the Sec translocation
      pathway. This implies that the nuclease should not be used as a reporter system
      in mycobacteria for the identification of exported products, despite what has
      been reported previously in the literature. The nuclease can be extended to
      create hybrid proteins that remain compatible with its secretion, whereas some
      other shorter fusions are not tolerated. This suggests that correct folding is
      required for efficient export. Extensive mutational analysis did not identify a
      specific secretion pathway. This suggests that the nuclease may be exported by
      different redundant systems or that components of this alternative Sec pathway
      are essential for bacterial survival.

PMID- 11832517
TI  - Chromosome loss from par mutants of Pseudomonas putida depends on growth medium
      and phase of growth.
AB  - The proteins encoded by chromosomal homologues of the parA and parB genes of many
      bacterial plasmids have been implicated in chromosome partitioning. Unlike their
      plasmid counterparts, mutant phenotypes produced by deleting these genes have so
      far been elusive or weakly expressed, except during sporulation. Here the
      properties of Pseudomonas putida strains with mutations in parA and parB are
      described. These mutants do not give rise to elevated levels of anucleate
      bacteria when grown in rich medium under standard conditions. However, in M9
      minimal medium different parA and parB mutations gave between 5 and 10% anucleate
      cells during the transition from exponential phase to stationary phase.
      Comparison of the DNA content of bacteria at different stages of the growth
      curve, in batch culture in L-broth and in M9-minimal medium, suggests that the
      par genes are particularly important for chromosome partitioning when cell
      division reduces the chromosome copy number per cell from two to one. This
      transition occurs in P. putida during the entry into stationary phase in M9
      minimal medium, but not in L-broth. It is proposed that the partition apparatus
      is important to ensure proper chromosome segregation primarily when the bacteria
      are undergoing cell division in the absence of ongoing DNA replication.

PMID- 11832519
TI  - Role of spoT-dependent ppGpp accumulation in the survival of light-exposed
      starved bacteria.
AB  - In bacteria, cytoplasmic levels of the effector nucleotide ppGpp are regulated in
      response to changes in growth conditions. This study describes the involvement of
      SpoT-mediated ppGpp accumulation in the survival of light-exposed bacteria during
      fatty acid starvation. In contrast to isogenic wild-type strains and relA
      mutants, the 'Vibrio angustum' S14 spoT and Escherichia coli relA spoT mutants
      displayed significant losses in viability in response to cerulenin-induced fatty
      acid starvation under cool-white fluorescent light. However, when starvation
      experiments were performed in complete darkness, or under light filtered through
      a UV-resistant perspex sheet, only a minor decline in viability was observed for
      the wild-type and mutant strains. This finding indicated that the lethal effect
      was mediated by weak UV emission. In contrast to the E. coli relA spoT mutant,
      which lacks ppGpp, the 'V. angustum' S14 spoT mutant exhibited higher ppGpp
      levels and lower RNA synthesis rates during fatty acid starvation, features that
      might be correlated with its lethality. In agreement with this finding, fatty
      acid starvation lethality also occurred upon induction of ppGpp overaccumulation
      in E. coli. These data suggest that the precise regulation of ppGpp levels in the
      stressed cell is crucial, and that both the absence and the overaccumulation of
      ppGpp impair fatty acid starvation survival of light-exposed cells. Moreover, the
      UV-induced lethal effect during fatty acid starvation was also observed for E.
      coli strains mutated in rpoS and dps, which, in the wild-type, are regulated
      directly or indirectly by ppGpp, respectively. The restoration of viability of
      fatty-acid-starved spoT mutant cells through the addition of exogenous catalase
      suggested that the observed light-dependent lethal effect was, at least in part,
      caused by UV-imposed oxidative stress. Based on these results, it is proposed
      that fatty acid starvation adaptation of light-exposed bacterial cells depends on
      the development of resistance to UV-induced oxidative stress. This stress
      resistance was found to require appropriate ppGpp levels, ppGpp-induced RpoS
      expression and, hence, upregulation of RpoS-regulated stress-defending genes,
      such as dps.

PMID- 11832520
TI  - Conserved aspartic acids are essential for the enzymic activity of the WecA
      protein initiating the biosynthesis of O-specific lipopolysaccharide and
      enterobacterial common antigen in Escherichia coli.
AB  - The integral membrane protein WecA mediates the transfer of N-acetylglucosamine
      (GlcNAc) 1-phosphate to undecaprenyl phosphate (Und-P) with the formation of a
      phosphodiester bond. Bacteria employ this reaction during the biosynthesis of
      enterobacterial common antigen as well as of many O-specific lipopolysaccharides
      (LPSs). Alignment of a number of prokaryotic and eukaryotic WecA-homologous
      sequences identified a number of conserved aspartic acid (D) residues in putative
      cytoplasmic loops II and III of the inner-membrane protein. Site-directed
      mutagenesis was used to study the role of the conserved residues D90, D91 (loop
      II), D156 and D159 (loop III). As controls, D35, D94 and D276 were also
      mutagenized. The resulting WecA derivatives were assessed for function by
      complementation analysis of O-antigen biosynthesis, by the ability to incorporate
      radiolabelled precursor to a biosynthetic intermediate, by detection of the
      terminal GlcNAc residue in LPS and by a tunicamycin competition assay. It was
      concluded from these analyses that the conserved aspartic acid residues are
      functionally important, but also that they participate differently in the
      transfer reaction. Based on these results it is proposed that D90 and D91 are
      important in forwarding the reaction product to the next biosynthetic step, while
      D156 and D159 are a part of the catalytic site of the enzyme.

PMID- 11832518
TI  - Role of the C-terminal YG repeats of the primer-dependent streptococcal
      glucosyltransferase, GtfJ, in binding to dextran and mutan.
AB  - The recombinant primer-dependent glucosyltransferase GtfJ of Streptococcus
      salivarius possesses a C-terminal glucan-binding domain composed of eighteen 21
      aa YG repeats. By engineering a series of C-terminal truncated proteins, the
      position at which truncation prevented further mutan synthesis was defined to a
      region of 43 aa, confirming that not all of the YG motifs were required for the
      formation of mutan by GtfJ. The role of the YG repeats in glucan binding was
      investigated in detail. Three proteins consisting of 3.8, 7.2 or 11.0 C-terminal
      YG repeats were expressed in Escherichia coli. Each of the three purified
      proteins bound to both the 1,6-alpha-linked glucose residues of dextran and the
      1,3-alpha-linked glucose residues of mutan, indicating that a protein consisting
      of nothing but 3.8 YG repeats could attach to either substrate. Secondary
      structure predictions of the primary amino acid sequence suggested that 37% of
      the amino acids were capable of forming a structure such that five regions of
      beta-sheet were separated by regions capable of forming beta-turns and random
      coils. CD spectral analysis showed that the purified 3.8 YG protein possessed an
      unordered secondary structure with some evidence of possible beta-sheet formation
      and that the protein maintained this relatively unordered structure on binding to
      dextran.

PMID- 11832522
TI  - Bacterial deposition in a parallel plate and a stagnation point flow chamber:
      microbial adhesion mechanisms depend on the mass transport conditions.
AB  - Deposition onto glass in a parallel plate (PP) and in a stagnation point (SP)
      flow chamber of Marinobacter hydrocarbonoclasticus, Psychrobacter sp. and
      Halomonas pacifica, suspended in artificial seawater, was compared in order to
      determine the influence of methodology on bacterial adhesion mechanisms. The
      three strains had different cell surface hydrophobicities, with water contact
      angles on bacterial lawns ranging from 18 to 85 degrees. Bacterial zeta
      potentials in artificial seawater were essentially zero. The three strains showed
      different adhesion kinetics and the hydrophilic bacterium H. pacifica had the
      greatest affinity for hydrophilic glass. On average, initial deposition rates
      were two- to threefold higher in the SP than in the PP flow chamber, possibly due
      to the convective fluid flow toward the substratum surface in the SP flow chamber
      causing more intimate contact between a substratum and a bacterial cell surface
      than the gentle collisions in the PP flow chamber. The ratios between the
      experimental deposition rates and theoretically calculated deposition rates based
      on mass transport equations not only differed among the strains, but were also
      different for the two flow chambers, indicating different mechanisms under the
      two modes of mass transport. The efficiencies of deposition were higher in the SP
      flow chamber than in the PP flow chamber: 62+/-4 and 114+/-28% respectively.
      Experiments in the SP flow chamber were more reproducible than those in the PP
      flow chamber, with standard deviations over triplicate runs of 8% in the SP and
      23% in the PP flow chamber. This is probably due to better-controlled convective
      mass transport in the SP flow chamber, as compared with the diffusion-controlled
      mass transport in the PP flow chamber. In conclusion, this study shows that
      bacterial adhesion mechanisms depend on the prevailing mass transport conditions
      in the experimental set-up used, which makes it essential in the design of
      experiments that a methodology is chosen with mass transport conditions
      resembling the problem under investigation.

PMID- 11832521
TI  - Genotyping of bacteria belonging to the former Erwinia genus by PCR-RFLP analysis
      of a recA gene fragment.
AB  - Genotypic characterization, based on the analysis of restriction fragment length
      polymorphism of the recA gene fragment PCR product (recA PCR-RFLP), was performed
      on members of the former Erwinia genus. PCR primers deduced from published recA
      gene sequences of Erwinia carotovora allowed the amplification of an
      approximately 730 bp DNA fragment from each of the 19 Erwinia species tested.
      Amplified recA fragments were compared using RFLP analysis with four
      endonucleases (AluI, HinfI, TasI and Tru1I), allowing the detection of
      characteristic patterns of RFLP products for most of the Erwinia species. Between
      one and three specific RFLP groups were identified among most of the species
      tested (Erwinia amylovora, Erwinia ananas, Erwinia cacticida, Erwinia cypripedii,
      Erwinia herbicola, Erwinia mallotivora, Erwinia milletiae, Erwinia nigrifluens,
      Erwinia persicina, Erwinia psidii, Erwinia quercina, Erwinia rhapontici, Erwinia
      rubrifaciens, Erwinia salicis, Erwinia stewartii, Erwinia tracheiphila, Erwinia
      uredovora, Erwinia carotovora subsp. atroseptica, Erwinia carotovora subsp.
      betavasculorum, Erwinia carotovora subsp. odorifera and Erwinia carotovora subsp.
      wasabiae). However, in two cases, Erwinia chrysanthemi and Erwinia carotovora
      subsp. carotovora, 15 and 18 specific RFLP groups were detected, respectively.
      The variability of genetic patterns within these bacteria could be explained in
      terms of their geographic origin and/or wide host-range. The results indicated
      that PCR-RFLP analysis of the recA gene fragment is a useful tool for
      identification of species and subspecies belonging to the former Erwinia genus,
      as well as for differentiation of strains within E. carotovora subsp. carotovora
      and E. chrysanthemi.

PMID- 11832523
TI  - Control of dimethylsulfoxide reductase expression in Rhodobacter capsulatus: the
      role of carbon metabolites and the response regulators DorR and RegA.
AB  - Regulation of the expression of dimethylsulfoxide (DMSO) reductase was
      investigated in the purple phototrophic bacterium Rhodobacter capsulatus. Under
      phototrophic, anaerobic conditions with malate as carbon source, DMSO caused an
      approximately 150-fold induction of DMSO reductase activity. The response
      regulator DorR was required for DMSO-dependent induction and also appeared to
      slightly repress DMSO reductase expression in the absence of substrate. Likewise,
      when pyruvate replaced malate as carbon source there was an induction of DMSO
      reductase activity in cells grown at low light intensity (16 W m(-2)) and again
      this induction was dependent on DorR. The level of DMSO reductase activity in
      aerobically grown cells was elevated when pyruvate replaced malate as carbon
      source. One possible explanation for this is that acetyl phosphate, produced from
      pyruvate, may activate expression of DMSO reductase by direct phosphorylation of
      DorR, leading to low levels of induction of dor gene expression in the absence of
      DMSO. A mutant lacking the global response regulator of photosynthesis gene
      expression, RegA, exhibited high levels of DMSO reductase in the absence of DMSO,
      when grown phototrophically with malate as carbon source. This suggests that
      phosphorylated RegA acts as a repressor of dor operon expression under these
      conditions. It has been proposed elsewhere that RegA-dependent expression is
      negatively regulated by the cytochrome cbb3 oxidase. A cco mutant lacking
      cytochrome cbb3 exhibited significantly higher levels of phi[dorA::lacZ] activity
      in the presence of DMSO compared to wild-type cells and this is consistent with
      the above model. Pyruvate restored DMSO reductase expression in the regA mutant
      to the same pattern as found in wild-type cells. These data suggest that R.
      capsulatus contains a regulator of DMSO respiration that is distinct from DorR
      and RegA, is activated in the presence of pyruvate, and acts as a negative
      regulator of DMSO reductase expression.

PMID- 11832524
TI  - The Rhizobium leguminosarum bv. viciae VF39 gamma-aminobutyrate (GABA)
      aminotransferase gene (gabT) is induced by GABA and highly expressed in
      bacteroids.
AB  - A Rhizobium leguminosarum bv. viciae VF39 gene (gabT) encoding a gamma
      aminobutyrate (GABA) aminotransferase was identified, cloned and characterized.
      This gene is thought to be involved in GABA metabolism via the GABA shunt
      pathway, a theoretical bypass of the 2-oxoglutarate dehydrogenase complex.
      Mutants in gabT are still able to grow on GABA as a sole carbon and nitrogen
      source. 2-oxoglutarate-dependent GABA aminotransferase activity is absent in
      these mutants, while pyruvate-dependent activity remains unaffected. This
      indicates that at least two enzymes with different substrate specifities are
      involved in the GABA metabolism of R. leguminosarum bv. viciae VF39. The gabT
      promoter was cloned into a newly constructed, stable promoter-probe vector pJP2,
      suitable for the study of transcriptional GUS fusions in free-living bacteria and
      during symbiosis. Under free-living conditions the gabT promoter is induced by
      GABA and repressed by succinate. Transcriptional regulation is mediated by GabR
      in a repressor-like manner. During symbiosis with the pea host plant gabT is
      induced and highly expressed in the symbiotic zone. Nodules induced by gabT
      mutants, however, are still effective in nitrogen fixation.

PMID- 11832525
TI  - Images in clinical medicine. Malposition of dual-chamber pacemaker lead.

PMID- 11832526
TI  - Sleep apnea syndrome.

PMID- 11832527
TI  - Reduction in the incidence of type 2 diabetes with lifestyle intervention or
      metformin.
AB  - BACKGROUND: Type 2 diabetes affects approximately 8 percent of adults in the
      United States. Some risk factors--elevated plasma glucose concentrations in the
      fasting state and after an oral glucose load, overweight, and a sedentary
      lifestyle--are potentially reversible. We hypothesized that modifying these
      factors with a lifestyle-intervention program or the administration of metformin
      would prevent or delay the development of diabetes. METHODS: We randomly assigned
      3234 nondiabetic persons with elevated fasting and post-load plasma glucose
      concentrations to placebo, metformin (850 mg twice daily), or a lifestyle
      modification program with the goals of at least a 7 percent weight loss and at
      least 150 minutes of physical activity per week. The mean age of the participants
      was 51 years, and the mean body-mass index (the weight in kilograms divided by
      the square of the height in meters) was 34.0; 68 percent were women, and 45
      percent were members of minority groups. RESULTS: The average follow-up was 2.8
      years. The incidence of diabetes was 11.0, 7.8, and 4.8 cases per 100 person
      years in the placebo, metformin, and lifestyle groups, respectively. The
      lifestyle intervention reduced the incidence by 58 percent (95 percent confidence
      interval, 48 to 66 percent) and metformin by 31 percent (95 percent confidence
      interval, 17 to 43 percent), as compared with placebo; the lifestyle intervention
      was significantly more effective than metformin. To prevent one case of diabetes
      during a period of three years, 6.9 persons would have to participate in the
      lifestyle-intervention program, and 13.9 would have to receive metformin.
      CONCLUSIONS: Lifestyle changes and treatment with metformin both reduced the
      incidence of diabetes in persons at high risk. The lifestyle intervention was
      more effective than metformin.

PMID- 11832528
TI  - Benefit of atrial pacing in sleep apnea syndrome.
AB  - BACKGROUND: Many patients with sleep apnea syndrome have nocturnal bradycardia,
      paroxysmal tachyarrhythmias, or both, which can be prevented by permanent atrial
      pacing. We evaluated the effect of using cardiac pacing to increase the heart
      rate during sleep in patients with sleep apnea syndrome. METHODS: We studied 15
      patients (11 men and 4 women; mean [+/-SD] age, 69+/-9 years) with central or
      obstructive sleep apnea who had received permanent atrial-synchronous ventricular
      pacemakers for symptomatic sinus bradycardia. All patients underwent three
      polysomnographic evaluations on consecutive nights, the first night for base-line
      evaluation and then, in random order, one night in spontaneous rhythm and one in
      dual-chamber pacing mode with atrial overdrive (basic rate, 15 beats per minute
      faster than the mean nocturnal sinus rate). The total duration and number of
      episodes of central or obstructive sleep apnea or hypopnea were analyzed and
      compared. RESULTS: The mean 24-hour sinus rate during spontaneous rhythm was 57
      +/- 5 beats per minute at base line, as compared with 72 +/- 3 beats per minute
      with atrial overdrive pacing (P<0.001). The total duration of sleep was 321 +/-
      49 minutes in spontaneous rhythm, as compared with 331 +/- 46 minutes with atrial
      overdrive pacing (P=0.48). The hypopnea index (the total number of episodes of
      hypopnea divided by the number of hours of sleep) was reduced from 9 +/- 4 in
      spontaneous rhythm to 3 +/-3 with atrial overdrive pacing (P<0.001). For both
      apnea and hypopnea, the value for the index was 28 +/- 22 in spontaneous rhythm,
      as compared with 11 +/- 14 with atrial overdrive pacing (P<0.001). CONCLUSIONS:
      In patients with sleep apnea syndrome, atrial overdrive pacing significantly
      reduces the number of episodes of central or obstructive sleep apnea without
      reducing the total sleep time.

PMID- 11832529
TI  - The emergence in Taiwan of fluoroquinolone resistance in Salmonella enterica
      serotype choleraesuis.
AB  - BACKGROUND: Salmonella enterica serotype choleraesuis is a cause of serious
      systemic infections. Because fluoroquinolones are the drug of choice for the
      treatment of severe salmonella infections, the emergence and dissemination of
      fluoroquinolone-resistant S. enterica serotype choleraesuis have clinical
      consequences. METHODS: In Taiwan, a hospital-based surveillance system has been
      in place since 1987 to monitor the incidence of S. enterica serotype choleraesuis
      infections and the antimicrobial susceptibility of the isolates. We investigated
      the rapid emergence of fluoroquinolone resistance in this serotype in 2000 and
      2001. Pigs in Taiwan were evaluated as a potential source of the resistant
      salmonella. RESULTS: A total of 501 clinical isolates of S. enterica serotype
      choleraesuis were recovered in our hospital from 1987 through 2000. The
      proportion of total salmonella isolates made up by S. enterica serotype
      choleraesuis decreased from an average of 8.4 percent before 1995 to 2.7 percent
      in 1996 through 1998. During 1999 and 2000, this proportion increased
      significantly, to an average of 5.0 percent. Ciprofloxacin resistance in S.
      enterica serotype choleraesuis has been observed since 2000. In the third quarter
      of 2001, 60 percent of isolates were resistant to ciprofloxacin. Molecular typing
      indicated that the primary source of S. enterica serotype choleraesuis isolates
      was herds of swine. All the resistant isolates from humans and swine had
      mutations that led to the substitution of phenylalanine for serine at position 83
      and asparagine for aspartic acid at position 87 in the gene for DNA gyrase A.
      CONCLUSIONS: This investigation in Taiwan indicates that fluoroquinolone
      resistant S. enterica serotype choleraesuis can spread from swine to humans. The
      use of fluoroquinolones in food animals should be prohibited.

PMID- 11832530
TI  - Expression of p53 and prognosis in children with malignant gliomas.
AB  - BACKGROUND: The prognosis of children with high-grade gliomas is uncertain, even
      when clinical and histologic findings are considered. We investigated whether
      mutations in the TP53 gene or the degree of expression of p53 protein in high
      grade gliomas is associated with progression-free survival in children with these
      tumors. METHODS: Paraffin-embedded specimens of malignant gliomas from children
      treated in the Children's Cancer Group study CCG-945 were assessed by mutational
      analysis of TP53 (121 specimens) and immunohistochemical analysis of p53 (115
      specimens). For mutational studies, areas of tissue that contained malignant
      glioma were isolated by microdissection, and the DNA was subjected to polymerase
      chain-reaction-based amplification and sequencing of TP53 exons 5, 6, 7, and 8.
      Immunohistochemical analysis was performed with the use of a microwave-enhanced
      antigen retrieval and an antibody that bound both wild-type and mutant p53.
      RESULTS: We found a significant association between overexpression of p53 and
      outcome; this association was independent of histologic features, age, sex, the
      extent of resection, and tumor location. The rate ( +/- SE) of progression-free
      survival at five years was 44 +/- 6 percent in the group of 74 patients whose
      tumors had low levels of expression of p53 and 17 +/- 6 percent in the group of
      41 patients whose tumors had overexpression of p53 (P<0.001). A nonsignificant
      association was observed between mutations in TP53 and outcome. CONCLUSIONS:
      Overexpression of p53 in malignant gliomas during childhood is strongly
      associated with an adverse outcome, independently of clinical prognostic factors
      and histologic findings.

PMID- 11832531
TI  - Images in clinical medicine. Aspergilloma as a complication of pacemaker
      implantation.

PMID- 11832532
TI  - Community-acquired pneumonia in children.

PMID- 11832533
TI  - Clinical problem-solving. More than your average wheeze.

PMID- 11832534
TI  - Cardiac pacing--a novel therapy for sleep apnea?

PMID- 11832536
TI  - The U.S. Attorney General's intrusion into medical practice.

PMID- 11832537
TI  - Legalized physician-assisted suicide in Oregon, 2001.

PMID- 11832538
TI  - Deep-brain stimulation in Parkinson's disease.

PMID- 11832539
TI  - B-type natriuretic peptide and acute coronary syndromes.

PMID- 11832540
TI  - Withholding proven treatment in research.

PMID- 11832541
TI  - Selective postoperative inhibition of gastrointestinal opioid receptors.

PMID- 11832542
TI  - Spironolactone and ACE inhibition in chronic renal failure.

PMID- 11832543
TI  - Tranexamic acid in hereditary hemorrhagic telangiectasia.

PMID- 11832544
TI  - Physician-assisted suicide in Oregon--an uncertain future.

PMID- 11832545
TI  - The combination of omeprazole, amoxycillin, and clarithromycin eradicates
      Helicobacter pylori in 95% of patients---7 days of therapy is as good as 10 days.
AB  - More than half of the known Helicobacter pylori strains are resistant to
      metronidazole, according to previous Hong Kong studies. The response rates to
      treatment regimens that comprise metronidazole as one of the antimicrobial agents
      have usually been disappointing in cases involving metronidazole-resistant
      strains. The objective of this open cohort evaluation was to assess the efficacy
      of an alternative regimen that combines omeprazole with amoxycillin and
      clarithromycin in Helicobacter pylor-positive ulcer and non-ulcer patients in
      Hong Kong. Furthermore, we aimed to investigate if 7 days were as good as 10 days
      of therapy. We studied 186 Helicobacter pylor-positive subjects; 149 subjects
      received 7 days of combination therapy and 37 subjects received 10 days. Our
      results showed that the overall Helicobacter pylori eradication efficiency was
      identical (94.6%) for both treatments. The incidences of adverse effects were
      also very similar (16.8% versus 16.2%) and both treatments were well tolerated.
      Thus, we propose that omeprazole in combination with amoxycillin and
      clarithromycin should be considered as one of the first-line therapies for
      patients with Helicobacter pylor infection in Hong Kong.

PMID- 11832546
TI  - The need for a clinical trials research methodology training programme in Hong
      Kong.
AB  - Training courses in the concepts of clinical trials research methodology that
      include rules in good clinical practice have not yet been extensively implemented
      in Hong Kong. This study aims to define the current knowledge of rules in good
      clinical practice and identify any need for such training programmes. Between May
      and August 1996, 161 clinical research staff were asked non-randomly to fill in a
      questionnaire about their knowledge of research methodology and their interest in
      specific courses. The median number of correctly answered questions (maximum
      score, 20) was 5 and the mode was 4, which was the expected score if questions
      had been answered randomly. Only minor differences in score were detected between
      doctors, research staff, and industry employees. Many researchers were keen,
      however, to further their knowledge by attending future courses; on average, each
      person showed an interest in three of the eight proposed courses. The study shows
      that the knowledge of rules in good clinical practice among clinical research
      staff in Hong Kong is poor, but there is nevertheless a demand for training
      programmes.

PMID- 11832547
TI  - Patients' knowledge of and attitudes towards anaesthesia and anaesthetists in
      Hong Kong.
AB  - We have performed a prospective, questionnaire-based survey on patients'
      knowledge of and attitudes towards anaesthetists in Hong Kong. Before their
      preoperative anaesthetic visit, 120 patients completed a three-section
      questionnaire. The first section consisted of questions designed to assess
      patients' knowledge about anaesthetists and their practice. The second section
      was designed to elicit their attitudes to anaesthetists and the third was a set
      of demographic questions. Seventy percent of patients recognised that
      anaesthetists are medical doctors and most realised that they provide anaesthesia
      for surgical procedures. However, there was scant knowledge of anaesthetists'
      perioperative role or their role in other aspects of patients care such as pain
      management, intensive care, resuscitation, research, and teaching. Patients felt
      it was important to be fully informed about the anaesthetic, and were keen to see
      their anaesthetist both preoperatively and postoperatively.

PMID- 11832548
TI  - Effectiveness of calcium acetate as a phosphate binder in patients undergoing
      continuous ambulatory peritoneal dialysis.
AB  - We compared the effectiveness of calcium acetate as a phosphate binder with that
      of calcium carbonate by substituting one for the other in patients undergoing
      continuous ambulatory peritoneal dialysis. Twenty patients who had been receiving
      calcium carbonate as a phosphate binder were instead given calcium acetate,
      initially with two thirds of the previous dose of elemental calcium. The calcium
      acetate dose was adjusted to achieve adequate calcium-phosphate balance; 65.6% of
      the previous dose of elemental calcium in calcium carbonate was required.
      Eighteen of the 20 patients completed the 3-month study. There were no
      significant differences in the pre-study and study levels of serum phosphate
      (1.81plus minus0.04 [SEM] versus 1.89plus minus0.06 mmol/L), corrected serum
      calcium (2.54plus minus0.04 versus 2.57plus minus0.03 mmol/L), calcium phosphate
      product (4.60plus minus0.15 versus 4.87plus minus0.18), serum alkaline
      phosphatase (64.75plus minus4.17 versus 69.94plus minus3.77 U/L), and serum
      parathyroid hormone (122plus minus31 versus 124plus minus27 ng/L). Three patients
      developed a total of five episodes of hypercalcaemia (corrected calcium level
      greater-than-or-equal2.85 mmol/L) and four other patients developed
      gastrointestinal upset. Calcium acetate can thus achieve similar phosphate
      control to calcium carbonate, using 65.6% of the dose of elemental calcium in
      calcium carbonate; however, its clinical superiority was not demonstrated in this
      study.

PMID- 11832549
TI  - Lack of structural rearrangement in c-kit and stem cell factor genes in Hong Kong
      Chinese patients with myelodysplastic syndromes or acute myeloid leukaemia.
AB  - Stem cell factor is a haemopoietic growth factor that interacts with the c-kit
      encoded transmembrane tyrosine kinase receptor during signal transduction in
      haemopoietic progenitor stem cells. We have screened 127 Chinese patients with
      myelodysplastic syndromes or acute myeloid leukaemia for structural
      rearrangements in the stem cell factor and c-kit genes using Southern blot
      analysis. No structural rearrangements were detected in any of the bone marrow
      samples that were tested. It seems that structural rearrangements in the stem
      cell factor and c-kit genes are rare in Hong Kong patients who have a
      haematological malignancy.

PMID- 11832550
TI  - Scleredema in Chinese patients: a local retrospective study and general review.
AB  - The records from 12 Chinese adult patients with scleredema, who had attended the
      Social Hygiene Service of the Hong Kong Department of Health between 22 January
      1990 and 19 March 1996, were retrieved and analysed. The neck was the commonest
      site of involvement (75%), followed by the back (42%), and the shoulder (17%).
      The vast majority (83%) of scleredema cases were associated with diabetes
      mellitus; half of these were insulin-dependent. Most of the patients (92%) had
      hypertension for which medical treatment was needed. No cases of skin disease
      were preceded by acute infection, and none had any associated paraproteinaemia.
      The degree of skin involvement did not affect the daily activities of most of the
      patients. This study revealed differences between the disease in our locality and
      those described in the western literature.

PMID- 11832551
TI  - Percutaneous transluminal angioplasty for stenosis of arteriovenous fistulae: a
      review of local experience.
AB  - The stenosis and subsequent thrombosis of the arteriovenous fistulae may lead to
      a loss of vascular access sites; this a major problem in chronic haemodialysis
      patients. Percutaneous transluminal angioplasty has been a popular way of
      correcting such lesions in recent years. We have reviewed patients who underwent
      this operation from 1993 to 1996 at the Queen Mary Hospital. Among 11 patients
      who were documented as having arteriovenous fistula stenosis, 60% of lesions were
      in the anastomotic area while 40% were in the venous limb. All patients had
      abnormal dialysis blood line pressures corresponding to the actual site of
      stenosis. The initial success rate of percutaneous transluminal angioplasty in
      treating the stenotic lesions was 73%. This method is thus a promising form of
      semi-invasive treatment for symptomatic arteriovenous fistula stenosis.

PMID- 11832552
TI  - Modern management of intrauterine growth retardation.
AB  - Management of intrauterine growth retardation is an important issue in obstetric
      practice. Since the introduction of Doppler ultrasonography, the problems
      associated with screening, diagnosing, monitoring, and identifying foetuses at
      risk have decreased in recent years. Owing to the use of Doppler ultrasonography,
      there is now a trend towards early delivery.

PMID- 11832553
TI  - Emergency defibrillation performed by coronary nursing staff: A pilot report.
AB  - The time taken to initiate defibrillation is a key factor in determining survival
      after cardiac arrest; all first-responding medical or paramedical personnel are
      thus recommended to receive training in defibrillation skills. We have recently
      established a working programme that allows trained coronary care nurses to
      defibrillate in emergencies. Prospective data collected from 1 October 1996 to 31
      January 1997 showed that a total of 11 witnessed episodes of ventricular
      fibrillation or pulseless ventricular tachycardia occurred in nine patients, and
      were defibrillated by nurses. All the defibrillations were started within 1
      minute of cardiac arrest. In five patients, defibrillation was commenced before
      the arrival of the crash team of doctors; three of the five patients survived.
      There were no violations of the resuscitation protocol or complications relating
      to defibrillation. Through programmed training in advanced cardiac life-support,
      coronary care nurses are capable of providing safe and prompt defibrillation. The
      importance of training and re-certification is also stressed.

PMID- 11832554
TI  - Streptococcal toxic shock-like syndrome in a post-myomectomy patient.
AB  - We report on a healthy 34-year-old woman who received an elective myomectomy for
      uterine fibroid, and postoperatively developed fatal streptococcal toxic shock
      like syndrome. We discuss the series of events that led to this life-threatening
      disease and its pathophysiology, and suggest areas in which management might have
      been improved.

PMID- 11832555
TI  - Penicillium marneffei infection and solitary pulmonary nodule.
AB  - We report on a patient infected with human immunodeficiency virus who presented
      with fever, a solitary pulmonary nodule, and cervical lymphadenopathy. The
      diagnosis of Penicillium marneffei infection was made from an excisional lymph
      node biopsy and a sputum culture. The microbiology, pathology, diagnosis, and
      treatment of the case are discussed. A high level of clinical suspicion is
      necessary for making an early diagnosis and improving the outcome of infection.

PMID- 11832556
TI  - A case of colonic tuberculosis mimicking Crohn's disease.
AB  - A 26-year-old Thai woman who has lived in Hong Kong for the past 3 years
      presented with a 2-month history of feverishness, intermittent epigastric
      discomfort, anorexia, and weight loss. She had had per rectal bleeding for 10
      days. Colonoscopy on two separate occasions revealed multiple ulcerations
      involving the entire colon, with rectal sparing. Histological examination of the
      two sets of colonic biopsies that were obtained during colonoscopy suggested
      Crohn's disease. There was no response to mesalazine and metronidazole, but the
      patient responded promptly to a therapeutic trial of antituberculous drugs.
      Cultures from the first set of colonic biopsies were negative for acid-fast
      bacilli, but 8 weeks after the second colonoscopy, cultures from the second set
      of biopsies yielded Mycobacterium tuberculosis. This case illustrates that the
      diagnosis of colonic tuberculosis requires a high index of suspicion. In cases
      where the information available does not reveal a definite differentiation
      between colonic tuberculosis and Crohn's disease, corticosteroids should be
      withheld. The administration of corticosteroids to a patient with colonic
      tuberculosis may have disastrous results, and a therapeutic trial of
      antituberculous drugs should be considered instead.

PMID- 11832557
TI  - A 24-year-old man with cerebral infarction.

PMID- 11832558
TI  - The historical development of dentistry in Hong Kong.
AB  - Dentistry in Hong Kong during this century has advanced from an informal
      streetside practice to a discipline that now serves the community by way of
      registered oral health care personnel. Throughout the years, public attitudes
      towards dental care have also changed: from a palliative approach involving the
      extraction of teeth when pain arose, to the prevention of dental disease even at
      the formative stage of dentition through water fluoridation, regular therapeutic
      care, and oral health maintenance. The education and professionalisation of
      practitioners has evolved from apprenticeship to the establishment of a
      structured university curriculum and postgraduate specialist training of
      international standards.

PMID- 11832559
TI  - The healing hand in literature: Shakespeare and surgery.
AB  - The interplay between surgery and dramatic literature in the plays of Shakespeare
      is reviewed. This review attempts to explore medical references in Shakespeare's
      works and to analyse the medical and social background of his time. Caution
      should be taken in interpreting Shakespeare's works through a modern medical
      view; diseases and their therapy are used metaphorically as a means to an end in
      the Bard's masterly hands. Shakespeare's medical knowledge may be accounted for
      by his avid reading of contemporary medical texts, from primary or secondary
      sources; an astute sense of observation of London's medical practitioners---bona
      fide or otherwise---and their activities and patients; and a medical connection
      by way of his son-in-law, Dr John Hall. It should be remembered that nothing in
      Nature stands alone; but every art and science has a relation to some other art
      or science, that it requires us to have a knowledge of those others, as this
      connexion takes place, to enable us to become perfect in that which engages our
      particular attention. John Hunter (1728-93)

PMID- 11832560
TI  - Acquired inhibitor to factor VIII causing upper-airway obstruction.

PMID- 11832561
TI  - Scientific evidence-based medical practice: where now?

PMID- 11832562
TI  - Why are thalassaemia patients born when prenatal screening is available?
AB  - Thalassaemia major is a classic example of a disease that is preventable by
      prenatal diagnosis. Although the technology was introduced to Hong Kong more than
      a decade ago, new patients are continuously seen in the Hong Kong Administrative
      Region. This retrospective review concerns children who were diagnosed to have
      severe beta-thalassaemic syndromes at the Tuen Mun Hospital from 1990 to 1996.
      Seventeen children (including a pair of identical twins) with homozygous beta
      thalassaemia and five children with double heterozygous beta-E thalassaemia were
      identified. All except three children were transfusion-dependent. Thirty-six
      parents were available for the thalassaemic study. Thirty-one of them had beta
      thalassaemic traits and the other five were carriers of haemoglobin E. Two of the
      parents with beta-thalassaemic traits and all five haemoglobin E carriers had a
      mean corpuscular volume above the cut-off for screening in antenatal diagnosis
      (>75 fL). Of the 21 at-risk pregnancies, seven were managed by public hospitals,
      11 by maternal and child health centres, and two by private practitioners.
      Thalassaemia had not been diagnosed prenatally because of the lack of maternal
      screening (n=9), lack of paternal screening (n=3), late antenatal visit (n=7),
      and parental refusal (n=1). Thus, many of our patients are not benefiting from
      the availability of prenatal screening.

PMID- 11832563
TI  - Bilevel positive airway pressure nasal mask ventilation in patients with acute
      hypercapnic respiratory failure.
AB  - The efficacy and complications of bilevel positive airway pressure nasal mask
      ventilation for 22 patients with acute hypercapnic respiratory failure were
      reviewed retrospectively. The median patient age was 73 years (range, 57-92
      years). The most common primary diagnosis (77%) was chronic obstructive pulmonary
      disease. The median duration of ventilation was 72.0 hours (range, 0.9 hours to
      35 days). Within a median of 12 hours (range, 1-24 hours) after the initiation of
      therapy, there were significant improvements in the arterial oxygen and carbon
      dioxide tensions, oxygenation ratio, and arterial-alveolar ratio. Fourteen
      patients (64%) were treated successfully. Success with therapy was associated
      with a lower Acute Physiology and Chronic Health Evaluation score, a higher
      arterial oxygen tension, higher oxygenation and arterial-alveolar ratios, and
      lower respiratory and pulse rates. Complications were uncommon. We conclude that
      bilevel positive airway pressure nasal mask ventilation can be useful for
      patients with acute hypercapnic respiratory failure but who are otherwise
      clinically stable.

PMID- 11832564
TI  - Nasopharyngeal carcinoma---time lapse before diagnosis and treatment.
AB  - This is a descriptive study of 168 patients with nasopharyngeal carcinoma who
      were referred to public oncology departments for primary treatment between July
      and September 1996. The mean duration from the onset of the symptoms to
      histological diagnosis was 5.0 months; the duration ranged from 6.1 months (for
      patients presenting with nasal symptoms) to 1.8 months (for those with cranial
      nerve dysfunction). The mean period between the onset of symptoms and the seeking
      of medical advice was 2.9months. For 54% of the patients, there was a further
      delay of up to 2.4 months between the initial medical consultation and referral
      to the appropriate specialist. The majority (84%) of patients attended public
      institutions for histological confirmation. The mean total time taken from the
      onset of symptoms to the commencement of radiotherapy was 6.5 months (range, 1.3
      74.0 months)---45% of the delay was attributed to the patient, 20% to initial
      consultations, 14% to diagnostic arrangement, and 21% to preparation for
      radiotherapy. Concerted efforts are needed to minimise further the time between
      the onset of symptoms and treatment. A substantial reduction in this delay can be
      achieved if both public and primary care doctors were made more aware of the
      significance of relevant symptoms.

PMID- 11832565
TI  - Travel, sexual behaviour, and the risk of contracting sexually transmitted
      diseases.
AB  - This study investigates sexual behaviour and the risk of contracting sexually
      transmitted diseases among travellers departing from Hong Kong, with an aim
      supporting the design of local intervention in continuing health promotion.
      Travellers were interviewed by five trained multilingual interviewers in the
      departure lounge at Kai Tak International Airport, Hong Kong, between May and
      June 1996, by using a structured, pretested questionnaire. Forty-four percent
      (168/383) of the respondents who travelled at least once within the previous year
      had had sex with strangers during their travel and 37% (139/376) of the
      respondents reportedly do not use condoms during sexual intercourse. Middle-aged
      and married travellers were more likely to be in the high-risk group. These
      findings reflect the urgent need to target travellers in any strategy that is
      designed to prevent the spread of sexually transmitted diseases in Hong Kong and
      Asia Pacific region.

PMID- 11832566
TI  - The use of anti-ribosomal P antibodies in the diagnosis of cerebral lupus--
      superiority of western blotting over enzyme-linked immunosorbent assay.
AB  - This study investigated the use of anti-ribosomal P antibodies in the diagnosis
      of cerebral complications of systemic lupus erythematosus using two different
      methods---western blotting and enzyme-linked immunosorbent assay. Anti-ribosomal
      P antibodies in patient serum were detected in both methods using a purified
      ribosomal P antigen substrate. Western blotting detected anti-ribosomal P
      antibodies with a 90% specificity for systemic lupus erythematosus in 56% of
      patients with the disease. The detection of anti-ribosomal P antibodies by
      western blotting in patients with systemic lupus erythematosus was significantly
      associated with psychosis and/or seizures; detection was positive in 90% of
      patients with these cerebral complications and in 41% of those without. Elevation
      of the level of anti-ribosomal P antibody, as measured by enzyme-linked
      immunosorbent assay, was 99% specific for systemic lupus erythematosus in 44% of
      patients with systemic lupus erythematosus that was not associated with cerebral
      involvement. We conclude that the measurement of anti-ribosomal P antibodies by
      western blotting is helpful in the diagnosis of cerebral lupus in selected
      patients.

PMID- 11832567
TI  - Evidence-based medical practice: as viewed by a clinical epidemiologist.
AB  - Evidence-based medicine shifts the basis for clinical decision making from
      intuition and unsystematic clinical experience to the examination of evidence
      resulting from clinical research. Evidence-based medicine is the same as good
      clinical research. The selection of a proper study design for a specific study
      objective is the most important cornerstone of good clinical research. Evidence
      based medicine places great importance on the design of a study, with optimum
      evidence being obtained from the randomised, controlled clinical trial. However,
      various study designs are equally important-if properly used-in the process of
      searching for solid and important evidence for use in clinical practice. There
      should be an emphasis on a quality improvement shift in research design from
      retrospective to prospective, cross-sectional to longitudinal, uncontrolled to
      controlled, and non-randomised to randomised. The reasons for using suboptimal
      study designs in clinical research are the lack of formal research training and
      the pressure to obtain academic output without being motivated. Research design
      is one of the most important aspects to study and practice, and there are four
      simple rules: (1) avoid retrospective studies; (2) focus on prospective studies;
      (3) use controls, randomisation, and blinding; and (4) always discuss the
      research design with an experienced researcher or statistician before commencing
      the study.

PMID- 11832568
TI  - Appraising published claims about drug treatment to implement best therapy in
      clinical practice.
AB  - The validity and applicability of publications about individual clinical studies
      and systematic overviews regarding interventions with drugs need to be
      established and perceived in quantitative terms to implement evidence-based, best
      current therapy. This requires an understanding of study design, various types of
      bias, intention to treat analysis, clinical versus statistical significance, and
      other considerations. The quantitative appreciation of drug effects may be
      facilitated by arranging results from case-control studies, cohort studies, and
      controlled trials in suitable contingency tables. Relative risks, relative risk
      reductions, odds ratios, and absolute risk reductions (in a given period of
      time), as well as corresponding numbers needing treatment (to prevent one event)
      may then be calculated. Systematic overviews of multiple clinical trials and
      assessment of their combined quantitative significance (meta-analyses) were
      developed to enhance statistical power, to enhance the level of confidence about
      small differences in effect, and to reconcile conflicting claims. The results of
      a meta-analysis are usually represented by so-called 'forest plots' of point
      estimates (corresponding to medians) and their respective confidence intervals,
      as well as a combined point estimate and confidence interval. Heterogeneity
      (important differences between findings from individual trials is a special
      problem incurred with this relatively new tool. The meta-analysis are also
      specially prone to other special sources of bias-a greater likelihood that trials
      reporting 'favourable' effects are published, covert duplicate inclusion of
      results from the same patients, and non-blinded meta-analysers.

PMID- 11832569
TI  - Evidence-based medical practice: ethical considerations.
AB  - The practice of medicine according to ethical principles requires that decisions
      regarding treatment, preventive or interventional strategies, or quality of life
      of patients in relation to life-support treatment should be based on evidence as
      far as possible. Available evidence for Hong Kong is reviewed under the following
      categories: use of drugs, management strategies, service provision, and
      interventions to prevent disease and/or disability. These examples highlight the
      need for studies to obtain evidence in the local population, as findings from
      studies in other countries may not be applicable. Although evidence exists in
      many areas to guide practice, the biggest challenge is how to implement such
      practice to ensure equitable access to prevention and treatment, particularly in
      the presence of health care resource limitations.

PMID- 11832570
TI  - Evidence-based medical practice: as viewed by a clinical researcher.
AB  - In this era of information technology, clinicians need to understand how to
      conduct ethical and effective clinical research. The principles of 'good clinical
      practice' have been established to prevent mistakes and malpractice, and to
      protect research subjects. A researcher must carefully design the study and
      perform a thorough review of the literature. A detailed protocol that has been
      approved by the institution's Ethics Committee must be constructed before
      commencement of the study and followed accordingly. Comparable control group(s),
      recruited in a double-blind fashion, ensure that the effects observed are
      specific to the intervention itself. While a retrospective data review is
      sometimes useful, only prospective studies provide solid evidence. Outcome
      parameters must be defined that are clinically appropriate and measurable.
      Subjects should only be recruited with consent and in a randomised fashion.
      Elimination of inter- and intra-observer errors can be achieved by appointing an
      assessor (or team) and by training personnel. Proper documentation of all the
      events and outcome parameters is of paramount importance and is a requirement for
      good clinical practice. Data analysis should be done by a qualified and
      experienced biostatistician and the personnel involved in the study must be fully
      aware of their moral, legal, and scientific responsibilities and be able to work
      with each other.

PMID- 11832571
TI  - Teaching evidence-based medicine.
AB  - The practice of evidence-based medicine is inherently pedagogical by its nature,
      requiring one to use tools that are basic lifelong learning skills. To facilitate
      the teaching of these skills, it is important to emphasise how the average Hong
      Kong practitioner's difficulty in keeping abreast of the rapidly growing body of
      medical literature can be efficiently resolved by using evidence-based medicine
      protocols. Four evidence-based medicine workshops were recently offered in Hong
      Kong. These workshops were organised and taught in a manner similar to one that
      had been found to be effective in other settings. Issues related to both the
      strengths and shortcomings of using this strategy in the local context are
      discussed. Implications for organising future workshops of this kind are also
      identified.

PMID- 11832572
TI  - The likely implications of the 1997 Coroners Ordinance on the autopsy service of
      a teaching hospital.
AB  - The new Hong Kong Coroners Ordinance was published in April 1997. It introduced
      an expanded set of guidelines for reporting deaths to the coroner as well as the
      threat of criminal proceedings for non-compliance. The Ordinance is due to be
      implemented in early 1998. The aim of this study is to determine the likely
      effect of the new law on the relative proportion of coroner's and hospital
      (consent) autopsies. A total of 352 consecutive autopsy cases were reviewed; 170
      (48.3%) were referred for coroner's autopsies and 182 (51.7%) for hospital
      autopsies. But applying the criteria of the current ordinance, there should have
      been 213 (60.5%) coroner's cases and 139 (39.5%) hospital autopsies-that is, 43
      hospital autopsies should have been coroner's autopsies. Under the new Coroners
      Ordinance, there would be 300 (85.2%) coroner's autopsies and only 52 (14.8%)
      hospital autopsies. The new Coroners Ordinance is likely to result in a greater
      number of requests for coroner's autopsies with a corresponding decline in
      hospital autopsies---in our case, a shift from 48.3% of all autopsies performed
      to 85.2%! This increase would be due largely to the requirement for reporting
      stillbirths but would also be due to increased reporting for fear of 'criminal
      proceedings' for non-compliance. An absolute increase in the number of autopsies
      is also anticipated, although the magnitude cannot as yet be predicted.

PMID- 11832573
TI  - The prevention of youth suicide: research and services.
AB  - In parallel with the escalating concern about youth suicides in the 1970s in the
      West, came an increase in suicide prevention efforts. The production of research
      data in the past 20 years enables us to evaluate the rationale and effectiveness
      of these suicide prevention programmes. Effective prevention programmes for youth
      suicide depend on our knowledge of the scope of the problem, factors associated
      with its occurrence, and an evaluation of the existing prevention strategies. The
      aim of this article is to review the main body of knowledge on the prevalence of
      and risk factors for youth suicide (both completed and attempted suicides) and
      use these to assess various prevention programmes.

PMID- 11832574
TI  - Eclampsia-an 11-year experience.
AB  - A retrospective study of all deliveries from 1983 to 1993 at the Tsan Yuk
      Hospital to evaluate the incidence was performed and outcome of eclampsia.
      Eclampsia occurred in 12 patients. The incidence was approximately 2 per 10,000
      deliveries and was relatively constant during the study period. Most convulsions
      occurred during the intrapartum (41.7%) and post-partum (50.0%) periods, and
      about half of them had no warning signs. There were no maternal or perinatal
      deaths. Prophylactic anticonvulsants should be given to all patients with warning
      signs; however, eclampsia is not always preventable.

PMID- 11832575
TI  - The need to evaluate the clinical effectiveness of traditional Chinese medicine.
AB  - Traditional Chinese medicine is gaining increasing attention and popularity in
      Hong Kong. There is no doubt that traditional Chinese medicine as a system of
      medicine works; however, this does not imply that every therapy is efficacious.
      Prevention of the initiation and continuation of ineffective intervention is
      extremely important for the efficiency of any health care system. The evaluation
      of the clinical effectiveness of traditional Chinese medicine is thus a top
      priority. Efforts should be made to register all randomised trials in traditional
      Chinese medicine and to regularly review and disseminate the evidence from
      organised research. These actions are essential for the promotion and practice of
      evidence-based decision making in traditional Chinese medicine.

PMID- 11832576
TI  - Is in-patient management of diastolic blood pressure between 90 and 100 mm Hg
      during pregnancy necessary?
AB  - A randomised controlled trial was performed at the Queen Elizabeth Hospital to
      compare the effects and acceptance of routine in-patient versus out-patient
      management of diastolic blood pressure between 90 and 100 mm Hg in pregnant
      women. There were no significant differences in the establishment of the
      diagnosis of hypertension, development of severe hypertension or proteinuric
      hypertension, the number of women requiring obstetric interventions, or the
      neonatal outcome between the two groups. Antenatal hospital stay for the in
      patient group, however, was more than twice as long as for the out-patient group
      (difference in mean stay, 3.7 days; 95% confidence interval, 1.3-6.2). The number
      of hospitalisations in the in-patient group was almost four times greater than
      that in the out-patient group (difference in mean number of hospitalisations,
      1.7; 95% confidence interval, 1.2-2.2). The two groups did not differ in their
      levels of satisfaction of the overall management of blood pressure. Nevertheless,
      a greater proportion of women preferred to choose the same type of care among the
      out-patient group than among the in-patient group if they had hypertension in a
      future pregnancy (83.7% versus 51.2%; P<0.001). More women were dissatisfied
      about the number of admissions than on the frequency of out-patient care (40.5%
      versus 16.3%; P<0.001). We conclude that in-patient care, day care, or home
      monitoring should be individualised.

PMID- 11832577
TI  - Treatment of vitiligo with autologous epidermal transplantation using the roofs
      of suction blisters.
AB  - We report our experience of autologous epidermal transplantation for three
      patients with vitiligo. The vitiligo in two patients was stable whereas that in
      the third was active. Autologous epidermal transplantation using suction blister
      roofs from normally pigmented skin was performed following the failure to
      repigment skin using topical steroid and/or psoralen-ultraviolet A treatment.
      Grafts were well taken in all three patients. Satisfactory repigmentation was
      noted in the two patients who had stable vitiligo; there were no complications
      except for mild hyperpigmentation at the donor areas. For the patient who had
      active vitiligo, depigmentation of the graft and concomitant Koebner's phenomenon
      at the donor site were observed 3 weeks after the procedure. We conclude that
      autologous epidermal transplantation using the roofs of suction blisters is an
      excellent and safe repigmenting procedure for stable, localised vitiligo and that
      active disease precludes transplantation.

PMID- 11832578
TI  - A case of eosinophilic gastroenteritis.
AB  - Eosinophilic gastroenteritis is a rare disorder characterised by eosinophilic
      infiltration of the bowel wall and various gastrointestinal manifestations.
      Diagnosis requires a high index of suspicion and exclusion of various disorders
      that are associated with peripheral eosinophilia. We report on a woman who had a
      short history of abdominal pain and ascites, and who responded dramatically to a
      course of low-dose steroid.

PMID- 11832580
TI  - Acute Wernicke's encephalopathy complicating chronic gallstone ileus.
AB  - An autopsy performed on a 53-year-old man who had unrelieved obstruction of the
      small bowel due to gallstone ileus revealed morphological features that were
      typical of acute Wernicke's encephalopathy. The likely sequence of disease in
      this patient was the development of thiamine deficiency owing to the unrelieved
      intestinal obstruction, which resulted in the development of acute Wernicke's
      encephalopathy. A high clinical awareness is required for the diagnosis of acute
      Wernicke's encephalopathy in patients with malnutrition from any cause.

PMID- 11832579
TI  - Primary hyperparathyroidism in Hong Kong: an analysis of 44 cases.
AB  - Primary hyperparathyroidism is increasingly being diagnosed subsequent to the
      detection of hypercalcaemia using multichannel auto-analyser screening. This
      paper provides a local picture of the clinical presentation and management of
      primary hyperparathyroidism. A retrospective review was conducted of 44 patients
      with primary hyperparathyroidism who were treated at the Queen Elizabeth Hospital
      between January 1987 and July 1996. Twenty-five (56.8%) of the patients were
      asymptomatic. Only three (6.8%) patients gave radiograms that had features
      indicating primary hyperparathyroidism; seven (15.9%) had renal stones. The
      patients underwent one or more of the following localisation procedures:
      computerised tomography, ultrasonography, thallium-technetium subtraction
      scanning, and technetium Tc 99m sestamibi scanning. The latter method was the
      most sensitive (64.3%). Ten adenomas that could not be localised by any of these
      procedures were successfully removed during surgery. Surgery was successful in
      94.4% of cases and surgical outcome was comparable to that reported in the
      literature.

PMID- 11832581
TI  - Homogeneous cubic cylinder packings revisited.
AB  - A method of systematically enumerating homogeneous (i.e. symmetry-related)
      packings of equal cylinders is developed. 19 three-way packings with axes
      parallel to <100> and 40 four-way packings with axes parallel to <111> are
      described. Cubic 6-, 12- and 24-way packings are possible and examples are given
      with axes parallel to <210> and <421>.

PMID- 11832582
TI  - Excited-state structure by time-resolved X-ray diffraction.
AB  - X-ray crystallography has traditionally been limited to the study of the ground
      state structure of molecules and solids. Recent technical advances are removing
      this limitation as demonstrated here by a time-resolved stroboscopic study of the
      photo-induced 50 micros lifetime excited triplet state of the [Pt(2)(pop)(4)](4
      )ion [pop = pyrophosphate, (H(2)P(2)O(5))(2-)], performed at helium temperatures
      with synchrotron radiation. The shortening of the Pt-Pt bond by 0.28(9)A upon
      excitation is compatible with the proposed mechanism involving promotion of a Pt
      Pt antibonding dsigma* electron to a weakly bonding p orbital. The contraction is
      accompanied by a 3 degree molecular rotation. The time-resolved diffraction
      technique described here is applicable to reversible light-driven processes in
      the crystalline solid state.

PMID- 11832583
TI  - One-dimensional scattering in K-hollandite: theory and experiment.
AB  - This work comprises calculations using the Frenkel-Kontorova and double-chain
      models, which led to new results explaining the experimental diffraction pattern
      of K-hollandite. The use of a deformable host chain and a Lennard-Jones-like
      interchain interaction gives the best results. From these calculations, it can
      also be concluded that the guest as well as the host are deformed and that the
      system is pinned. The inclusion of Debye-Waller factors as fitting parameters is
      also discussed, with the conclusion they should not be used in the case of the
      double-chain model.

PMID- 11832584
TI  - X-ray four-quadrant diamond phase-retarder system to compensate for off-axis and
      chromatic aberrations.
AB  - An X-ray transmission-type double phase-retarder system that can compensate for
      off-axis aberration (phase-shift inhomogeneity due to angular divergence of
      incident X-rays) has been developed and its advantage over a conventional single
      transmission-type X-ray phase retarder was demonstrated. However, it was noticed
      that the transmission-type X-ray phase retarder suffers from not only off-axis
      aberration but also chromatic aberration (phase-shift inhomogeneity due to energy
      spread of incident X-rays). In this paper, a transmission-type X-ray four
      quadrant phase-retarder system is proposed that can compensate for both off-axis
      and chromatic aberrations. The X-ray four-quadrant phase-retarder system is
      composed of four transmission-type X-ray phase retarders. The scattering planes
      of four phase-retarder diamond crystals are set to be inclined by 45 degree, 135
      degree (= 45 degree + 90 degree), 225 degree (= 45 degree + 180 degree) and 315
      degree (= 45 degree + 270 degree), respectively, with respect to the plane of
      incident polarization. Under the conditions of 7709 eV photon energy, 1.5 eV
      energy spread and 45" angular divergence (FWHM) of incident X-rays, the X-ray
      four-quadrant phase-retarder system created 0.98 degree of vertical-linear
      polarization from horizontal-linear polarization. This value was favorably
      compared to 0.89 and 0.96, which were obtained by the single and double phase
      retarder systems, respectively. The principle of the X-ray four-quadrant phase
      retarder system will be described together with its advantage over the single and
      double phase-retarder systems.

PMID- 11832585
TI  - On the auxiliary lattices and dislocation reactions at triple junctions.
AB  - Coincidence site and displacement shift complete lattices of triple junctions are
      analysed. Dislocation reactions at triple junctions are considered. It is shown
      that in alpha=1 junctions no trapped residual triple-junction dislocation is
      geometrically necessary for dislocation transmission between adjoining grain
      boundaries. However, the situation is different for alpha (unequal) 1 triple
      junctions, where in some cases the residual dislocation cannot leave the triple
      junction for a grain boundary without generating a stacking-fault-like defect.

PMID- 11832586
TI  - Modeling chemical bonding effects for protein electron crystallography: the
      transferable fragmental electrostatic potential (TFESP) method.
AB  - This paper addresses the problem of determining the electrostatic potential of
      large proteins by the superposition of potentials calculated for small fragments.
      The use of different atomic and molecular fragments is considered for reproducing
      the molecular electrostatic potential of different conformations of N
      acetylalanine methylamide (NAAMA) with an acceptable degree of error as measured
      by conventional R factors used in crystallographic structure refinement. Three
      different divisions of NAAMA are tested, producing fragments that incorporate
      increasingly more complete descriptions of molecular bonding with diminishing
      accuracy in geometric fit to the parent molecule: single atoms in molecules,
      bonded atoms in molecules and selected functional groups, such as the backbone
      peptide moiety, or the alpha-carbon, beta-carbon and their associated H atoms. In
      the resolution range 2.5-25A, the fairly straightforward use of single atoms in
      molecules reduces the calculated R factors by 5-15% over a free-atom
      superposition. No significant further improvement was found at the lowest
      resolutions with a superposition of single bonds in molecules and R factors were
      found to degrade with larger fragments at higher resolutions because of poor
      geometry fits to the atoms of the parent molecule. Because the potential
      distribution even for single atoms depends on the environment, the best accuracy
      will be obtained by using a library of fragment potentials calculated for each
      type of atom as a function of important protein conformations.

PMID- 11832587
TI  - Analysis of polynuclear aromatic hydrocarbons via the Voronoi tessellation
      approach: classification of atom types using artificial neural networks.
AB  - When identifying the correct atom types to occupy the specific atomic locations
      within newly observed structures or when assessing the plausibility of new
      suggested structures with specific locations for specific types of atoms, any
      information quantifying geometrically the local environments around those
      locations is valuable, provided known characteristic differences exist, with
      respect to this geometric information, between the different atom types. A
      powerful tool for quantifying such geometries is the Voronoi tessellation; this
      has been used in a pilot study of polynuclear aromatic hydrocarbons. It has been
      found that perfect identification of all C and H atoms may be achieved through
      the examination of polyhedral volumes and surface areas. The use of a weighted
      face-area average is also found to be a useful measure of local structure. Simple
      neural network models that may be used for atom-type prediction are given in the
      paper. It is expected that the present approach will be useful in distinguishing
      between atoms that have close scattering curves whilst displaying similar
      crystallographic behaviour.

PMID- 11832588
TI  - General periodic average structures of decagonal quasicrystals.
AB  - The concept of periodic average structure is mutated from the theory of
      incommensurately modulated structures. For quasicrystals, this concept (up to now
      explored only in few cases) is becoming increasingly useful to understand their
      properties and to interpret some important structural features. The peculiar
      property of quasicrystals is that they admit not one but many (infinite) possible
      different average structures. Few of them, however, will be meaningful. Here are
      given a simple method (based on reciprocal space) for generating all the possible
      periodic average structures of decagonal quasicrystals and some new ideas about
      their meaning. By this method, the most significant average structures can be
      recognized from the diffraction pattern.

PMID- 11832589
TI  - Wavelength extrapolation to zero extinction: a gamma-ray case. The quantitative
      effect of the extrapolation function on the kinematical limit value.
AB  - To ensure that a true zero-extinction kinematical limit value has been attained
      by extrapolation of a series of measurements on one reflection, the proper
      dependence of a function of F versus the function of the physical variable
      involved in the measurements has to be identified. To demonstrate this point, the
      multiwavelength gamma-ray data on seven reflections of NiF(2) reported by Palmer
      & Jauch [Acta Cryst. (1995), A51, 662--667] have been utilized. A new physical
      component has been introduced into the relationship between diffracted intensity
      and wavelength--that due to the decrease in angular divergence of diffraction
      from crystallites with decrease in wavelength. For gamma-rays, this leads to a
      function of F(2) in respect of wavelength, viz F(2) = F(0)(2) - alphalambda +
      betalambda(2), which is different from that derived from Zachariasen-type models,
      viz F(2) = F(0)(2) - klambda(2). Comparison of the limit values according to
      Palmer & Jauch and according to Mathieson & Stevenson demonstrates the advantage
      of the functional dependence proposed in this study.

PMID- 11832590
TI  - Whole powder pattern modelling.
AB  - A new approach for the modelling of diffraction patterns without using analytical
      profile functions is described and tested on ball milled f.c.c. Ni powder
      samples. The proposed whole powder pattern modelling (WPPM) procedure allows a
      one-step refinement of microstructure parameters by a direct modelling of the
      experimental pattern. Lattice parameter and defect content, expressed as
      dislocation density, outer cut-off radius, contrast factor, twin and deformation
      fault probabilities), can be refined together with the parameters (mean and
      variance) of a grain-size distribution. Different models for lattice distortions
      and domain size and shape can be tested to simulate or model diffraction data for
      systems as different as plastically deformed metals or finely dispersed
      crystalline powders. TEM pictures support the conclusions obtained by WPPM and
      confirm the validity of the proposed procedure.

PMID- 11832591
TI  - Direct methods and isomorphous replacement. The triplet invariant estimate when
      heavy atoms are located.
AB  - The probabilistic theory of the three-phase structure invariants for isomorphous
      pairs has been generalized to the case in which a heavy-atom structure model is
      available. The rigorous method of joint probability distributions has been
      applied: it is able to handle errors in measurements and in the heavy-atom
      structure model, as well as the lack of isomorphism. The conclusive formulas have
      been successfully applied to experimental data.

PMID- 11832593
TI  - Comments on quasicrystalline phases and examples of quasicrystalline phase
      nomenclature in "Nomenclature of magnetic, incommensurate, composition-changed
      morphotropic, polytype, transient-structural and quasicrystalline phases
      undergoing phase transitions. II. Report of an IUCr Working Group on Phase
      Transition Nomenclature" by J.-C. Toledano et al. (2001). Acta Cryst. A57, 614
      626.

PMID- 11832595
TI  - Is syringomyelia pathology or a natural protective phenomenon?

PMID- 11832596
TI  - Use of static lung mechanics to identify early pulmonary involvement in patients
      with ankylosing spondylitis.
AB  - AIM: To assess if a detailed analysis of lung mechanics could help in early
      recognition of pulmonary abnormalities in patients with ankylosing spondylitis.
      METHODS: Static pulmonary mechanics were studied in 17 patients (16 men and one
      woman) of ankylosing spondylitis with no obvious clinical or radiological
      evidence of pulmonary involvement. Lung pressure-volume relationship was
      generated using a whole body plethysmograph, and a monoexponential equation
      fitted to this data. RESULTS: Total lung capacity (TLC) was reduced in one (5.9%)
      and static lung compliance (Cst) in nine (52.9%) patients. Four (23.5%) patients
      had normal TLC, yet Cst and shape constant (K) were reduced. Five (29.4%)
      patients had reduced TLC and Cst; four of them had low K. One (5.9%) patient had
      normal TLC but elevated Cst and K. CONCLUSIONS: Pulmonary involvement in patients
      with ankylosing spondylitis is probably diffuse and begins much earlier than
      generally presumed. Evaluation of static lung mechanics can identify pulmonary
      involvement early in the course of disease in several of these patients.

PMID- 11832597
TI  - Cutaneous adverse drug reactions: clinical pattern and causative agents--a 6 year
      series from Chandigarh, India.
AB  - AIM: To study the different clinical spectrum of cutaneous adverse drug reactions
      (ADR) and to determine the causative drugs. MATERIALS & METHODS: A prospective,
      hospital based study was carried out over a period of 6 years recording various
      cutaneous ADR. RESULTS: A total of 500 patients with cutaneous ADR were enrolled
      in the study. The most common types of cutaneous ADR patterns were maculopapular
      rash (34.6%), fixed drug eruption (FDE) (30%) and urticaria (14%). The drugs most
      often incriminated for the various cutaneous ADR were antimicrobials (42.6%),
      anticonvulsants (22.2%) and NSAIDs (18%). Anticonvulsants were implicated in
      41.6% of maculopapular rashes. Sulfonamides accounted for 43.3% and NSAIDs for
      30.7% of FDE. Urticaria was caused mainly by NSAIDs(24.3%) and penicillins(20%).
      Anticonvulsants were responsible for 43.8% of life-threatening toxic epidermal
      necrolysis and Stevens Johnson syndrome. CONCLUSIONS: The clinical pattern and
      drugs causing cutaneous ADR are similar to those observed in other countries
      except for minor variations. Cutaneous ADR patterns and the drugs causing various
      reactions are changing every year, which may be due to the emergence of newer
      molecules and changing trends in the use of drugs.

PMID- 11832598
TI  - Percutaneous tracheostomy by guidewire dilating forceps technique: review of 98
      patients.
AB  - BACKGROUND: Percutaneous tracheostomy to a large extent has replaced conventional
      surgical tracheostomy by virtue of its low incidence of complications and the
      rapidity with which the procedure can be performed at the bedside avoiding
      transport of critically ill patients to the operating rooms. Since it is a blind
      approach, bronchoscopic guidance has been suggested which might not always be
      possible due to logistic reasons. METHODS: A retrospective study of 98 patients
      who had guide wire dilating forceps technique of percutaneous tracheostomy
      without the aid of a bronchoscope was undertaken. By ensuring the free mobility
      of the guide wire at each step of the procedure, a safe placement of the
      tracheostomy tube was achieved. RESULTS: The mean operating time was 3.05 mins
      [S.D:2.20]. Two patients had peristomal bleeding as an early complication. 34
      patients could be decannulated with good primary approximation of the stomal
      tissues [mean: 3.92days, S.D: 1.46]. There were no deaths or life threatening
      complications attributable to this technique. CONCLUSIONS: In the absence of
      bronchoscopic guidance, adopting the simple but effective precaution of free
      movement of guide wire at each step of the procedure, a safe tracheostomy tube
      placement is possible.

PMID- 11832599
TI  - Pyrexia of unknown origin: a prospective study of 100 cases.
AB  - AIM: There are few studies on pyrexia of unknown origin (PUO) from India. The
      present study was planned to elucidate the causes of in PUO Eastern India and to
      define the changing patterns of PUO, if any. STUDY DESIGN: Prospective case
      series. PATIENTS: One hundred patients meeting the classic criteria of pyrexia of
      unknown origin. MAIN OUTCOME MEASUREMENT: The final diagnosis established at
      discharge or during follow up. RESULTS: Infections, especially tuberculosis was
      the most dominant cause (53%), followed by neoplasms (17%), and collagen vascular
      disorders (11%), Miscellaneous causes were responsible in 5% cases and in 14% the
      cause of fever remained undiagnosed. CONCLUSION: It is concluded that infections
      remain the most important cause of PUO in India, confirming the trends found
      earlier in other studies. The incidence of neoplasms was much higher compared to
      other studies from India.

PMID- 11832600
TI  - Iatrogenic gastric fistula due to inappropriate placement of intercostal drainage
      tube in a case of traumatic diaphragmatic hernia.
AB  - A 26-year-old, 30 weeks primigravida presented with a gastric fistula through a
      left intercostal drain, which was inserted for drainage of suspected
      haemopneumothorax following minor trauma. It was confirmed to be a diaphragmatic
      hernia, with stomach and omentum as its contents. On exploratory laparotomy,
      disconnection of the tube and fistulous tract, with reduction of herniated
      contents and primary suturing of stomach was carried out. Diaphragmatic
      reconstruction with polypropylene mesh was also carried out. Post-operative
      recovery was uneventful with full lung expansion by 3rd postoperative day.
      Patient was asymptomatic at follow-up 6 months.

PMID- 11832601
TI  - Idiopathic necrotising granulomatous interstitial nephritis.
AB  - We report a case of idiopathic necrotising granulomatous interstitial nephritis
      seen as an incidental autopsy finding in a 65 years female. The unusual features
      were the presence of necroses, with a florid, bizarre giant cell reaction. There
      were varying degrees of tubular damage, with relative sparing of glomeruli. There
      was no history of drug ingestion; Mycobacteria, fungi or crystals were not
      identified.

PMID- 11832602
TI  - Ovarian dysgenesis with balanced autosomal translocation.
AB  - Autosomal translocations are rare in the patients with ovarian dysgenesis. An 18
      year-old female who presented with primary amenorrhoea had hypergonadotropic
      hypogonadism and streak ovaries with hypoplastic uterus. Karyotype analysis
      revealed a balanced autosomal translocation involving chromosomes 1 and 11. The
      probable role of autosomal translocations in ovarian dysgenesis has been
      discussed.

PMID- 11832603
TI  - Diffuse calvarial meningioma: a case report.
AB  - A rare case of a diffuse calvarial meningioma in a sixty-three year-old female is
      reported. The patient presented with headache, painful proptosis and chemosis of
      the left eye. Imaging showed that the frontoparietal calvarium on both sides and
      the left orbital roof were thickened. The thickened bone showed patchy
      rarefaction. In relationship to the thickened bone, there was an enhancing en
      plaque meningioma. The tumour extended on to the superolateral aspect of the left
      orbit and resulted in proptosis. Excision of the left frontoparietal calvarium
      and the orbital tumour was performed. The management of diffuse calvarial
      meningioma is discussed and the relevant literature is briefly reviewed.

PMID- 11832604
TI  - Computers and vision.

PMID- 11832605
TI  - ICH Harmonised Tripartite Guideline: guideline for good clinical practice.

PMID- 11832606
TI  - A variant of Poland syndrome.

PMID- 11832607
TI  - Leiomyoma of the vas deferens.

PMID- 11832608
TI  - Pituitary metastases in carcinoma breast.

PMID- 11832609
TI  - Omentopexy for limb salvage in Buerger's disease: indications, technique and
      results.
AB  - Buerger's disease is a limb-threatening condition occurring in the young and
      productive age group and its management has always been a challenging problem. A
      large number of medical and surgical options have been suggested, but the quest
      for an ideal solution to this problem continues. Omentopexy for Buerger's disease
      is an attractive option, which is rapidly gaining popularity. We discuss the
      historical aspects, technical considerations and results of omental transfer for
      this limb-threatening condition. In doing so, the relevant literature on the
      subject has been extensively reviewed. In all published series, there has been
      marked improvement in intermittent claudication and rest pain. Ischaemic ulcers
      have healed and the progression of gangrene has stopped. If carried out with the
      complete understanding of the anatomy of the omental vascular arcade, the results
      of omentopexy are gratifying, thus avoiding amputation and conserving the limb.

PMID- 11832610
TI  - Near fatal haemoperitoneum of rare origin following laparoscopic sterilisation.

PMID- 11832611
TI  - Soft tissue swelling: cytology comes to rescue.

PMID- 11832612
TI  - Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry,
      India.

PMID- 11832613
TI  - Evolution of anaesthesia in India.

PMID- 11832614
TI  - End-tidal carbon dioxide monitoring in pediatrics: concepts and technology.

PMID- 11832615
TI  - Hypertrophic cardiomyopathy: the elusive terrorist?

PMID- 11832616
TI  - Hypertrophic cardiomyopathy: an autopsy analysis of 14 cases.
AB  - BACKGROUND: Hypertrophic cardiomyopathy (HCM) is one of the less common forms of
      primary cardiomyopathies. There is little data available on HCM in Indian
      literature. AIMS: To assess the incidence and analyse the clinicopathological
      features of HCM. SETTINGS: Analysis of data of 15 years from a tertiary care
      centre. METHODS AND MATERIAL: The clinical and pathological data in fourteen
      cases of HCM with respect to their gross and microscopic features and clinical
      presentation were reviewed. RESULTS: Incidence of HCM amongst the autopsied
      primary cardiomyopathies (N = 101) was 13.9% (n=14). Males were affected more.
      Common presenting symptoms were exertional dyspnoea, angina and palpitations.
      Concentric and asymmetric hypertrophy was equally seen. Obliterative small vessel
      disease was noted in 50% of the cases. Although significant myofibre disarray
      (>5%) was seen in all fourteen cases, it could be demonstrated in only 40- 50% of
      an average of twenty sections studied. Type IA myofibre disarray was the
      commonest. Six of the fourteen patients died suddenly. Cardiac failure was the
      commonest cause of death. CONCLUSIONS: Myofibre disarray is a highly sensitive
      and specific marker for HCM only when considered in a quantitative rather than a
      qualitative fashion. In this context, the rationale for performing endomyocardial
      biopsy is to rule out mimics of HCM.

PMID- 11832618
TI  - Symptomatic small non-obstructing lower ureteric calculi: comparison of
      ureteroscopy and extra corporeal shock wave lithotripsy.
AB  - OBJECTIVE: To compare the success, efficacy and complications of ureteroscopy
      (URS) and extra corporeal shock wave lithotripsy (ESWL) for the treatment of
      symptomatic small non obstructing lower ureteric calculi. SUBJECTS AND METHODS:
      This prospective non-randomised study was conducted simultaneously at two
      urological referral centres, included 280 patients with symptomatic small (4-10
      mm) lower ureteric calculi (situated below the sacroiliac joint), with good renal
      function on intravenous urography. Patients were offered both the treatment
      options. One hundred and sixty patients chose ureteroscopy, whereas 120 patients
      were treated by ESWL. Standard techniques of ureteroscopy and ESWL were employed.
      Patients were followed-up to assess the success rates and complications of the
      two procedures. RESULTS: Ureteroscopy achieved complete stone clearance in one
      session in 95% of patients. In six patients ureteroscopy had failed initially and
      was later accomplished in second session improving the success rate to 98.7%. Two
      patients had a proximal migration of calculus that needed ESWL. Of the 120
      patients treated by ESWL, 90% achieved stone free status at three months.
      Ureteroscopy was needed for twelve patients (10%) where ESWL failed to achieve
      stone clearance. There were no significant ESWL related complications. ESWL was
      administered on outpatient basis, while patients needed hospitalisation and
      anaesthesia for ureteroscopy. CONCLUSION: ESWL can be the primary mode of
      treatment for symptomatic small non-obstructing lower ureteric calculi as it is
      minimally invasive and safe. Ureteroscopy can be offered to patients who demand
      immediate relief or when ESWL fails.

PMID- 11832617
TI  - Oral cancer among patients under the age of 35 years.
AB  - BACKGROUND: Cancer of the oral cavity is one of the commonest cancers among
      males. AIMS: To assess the aetiological factors, patient characteristics,
      treatment and the outcome in young patients with oral cancer. SETTINGS AND
      DESIGN: A retrospective descriptive study of patients under the age of 35 years
      with cancer of the oral cavity treated between 1982-1996, with the last follow-up
      till 2001, using the tumour registry data of Regional Cancer Centre (RCC),
      Trivandrum, Kerala, India. SUBJECT AND METHOD: The detailed clinical, treatment
      and follow-up data were obtained from the computerised records of RCC and
      recorded on a preset proforma. This was analysed with emphasis on age, sex, risk
      factors, site, histology, clinical extent and treatment methods and survival in
      the study group. STATISTICAL ANALYSIS: The survival analysis was carried by
      Kaplan-Meier method and the difference in survival was analysed using log-rank
      test. RESULTS: Out of 264 patients analysed, tongue was the commonest site
      identified in 136 (52%) patients followed by buccal mucosa in 69 (26%) patients.
      A male female ratio of 2.3:1 was observed with a significantly higher male
      preponderance in buccal mucosa (4.3:1). Prior exposure to tobacco or alcohol was
      noted in 59.4% patients, with more habitues in buccal mucosa cancer. Histological
      confirmation was present only in 83.7% patients and among them most were squamous
      cell carcinoma (85.9%). Radiotherapy, surgery or combined modalities of treatment
      were employed for majority of patients. The 5-year survival was 57.3%. T stage of
      the tumour was found to be significant in predicting disease free survival
      (P=0.03). CONCLUSIONS: The importance of early detection for clinical down
      staging is stressed. There is a need to investigate the aetiology of intra oral
      cancers in younger patients since a significant proportion (almost 40%) of these
      patients do not have associated risk factors for cancer.

PMID- 11832619
TI  - Comparative evaluation of intraocular pressure changes subsequent to insertion of
      laryngeal mask airway and endotracheal tube.
AB  - AIMS: To evaluate the intraocular pressure and haemodynamic changes subsequent to
      insertion of laryngeal mask airway and endotracheal tube. SUBJECTS AND METHODS:
      The study was conducted in 50 adult patients. A standard general anaesthesia was
      administered to all the patients. After 3 minutes of induction of anaesthesia
      baseline measurements of heart rate, non-invasive blood pressure and intraocular
      pressure were taken following which patients were divided into two groups:
      laryngeal mask airway was inserted in group 1 and tracheal tube in group 2. These
      measurements were repeated at 15-30 second, every minute thereafter up to 5
      minutes after airway instrumentation. RESULTS: A statistically significant rise
      in heart rate, systolic blood pressure, diastolic blood pressure and intraocular
      pressure was seen in both the groups subsequent to insertion of laryngeal mask
      airway or endotracheal tube. Mean maximum increase was statistically more after
      endotracheal intubation than after laryngeal mask airway insertion. The duration
      of statistically significant pressure responses was also longer after
      endotracheal intubation. CONCLUSION: Laryngeal mask airway is an acceptable
      alternative technique for ocular surgeries, offering advantages in terms of
      intraocular pressure and cardiovascular stability compared to tracheal
      intubation.

PMID- 11832621
TI  - Morgagni hernia with Down syndrome: a rare association -- case report and review
      of literature.
AB  - Morgagni hernia is a rare diaphragmatic hernia accounting for only 2% of the
      congenital diaphragmatic defects. A case of Morgagni hernia was diagnosed
      radiologically in a 12-months-old male with Down syndrome, with recurrent
      respiratory distress and chest deformity. The 2-dimensional echocardiography was
      normal. The diagnosis of Morgagni hernia was confirmed by barium studies. The
      patient underwent a corrective surgery at 18 months of age following which his
      symptoms subsided. Literature review revealed only 18 cases of Morgagni hernia
      with Down syndrome reported till date, with age of presentation varying from
      neonatal age group to 12 years of age. The mode of presentations varied from
      asymptomatic detection to severe respiratory distress. The possible mechanism of
      association and its clinical implication has been discussed. The case emphasises
      a need for diaphragmatic hernia to be looked for as a possible cause of
      respiratory distress in Down syndrome.

PMID- 11832620
TI  - Cardiomediastinal tamponade and shock following three-stage transthoracic
      oesophagectomy.
AB  - Massive gastric tube dilatation causing cardiomediastinal tamponade is an unusual
      cause of obstructive shock after transthoracic oesophagectomy. A 55-year-old
      female was operated for total transthoracic oesophagectomy. Twelve hours after
      the surgery, she developed hypotension and raised central venous pressure
      unresponsive to fluid infusion and ionotropes. X-ray chest showed a massively
      dilated stomach, which was causing intrathoracic tamponade. Suction applied to
      the nasogastric tube led to aspiration of 150-200 ml of fluid and a large volume
      of air, which led to resolution of the haemodynamic instability. A simple
      manoeuvre like nasogastric suction in postoperative case of oesophagectomy can
      serve as a diagnostic as well as therapeutic tool. It must be performed before
      resorting to invasive and expensive examination or intervention.

PMID- 11832622
TI  - Cavernous haemangioma in the interpeduncular cistern: case report and review of
      literature.
AB  - A rare case of a cavernous haemangioma in the interpeduncular cistern is
      reported. The patient, forty-five year old male presented with excruciating left
      sided trigeminal neuralgia and diplopia for the past one year. Examination
      revealed left third and fifth nerve paresis. Magnetic resonance imaging showed a
      well-defined, lobulated tumour in the interpeduncular cistern. The tumour was
      totally excised through a subtemporal route. Histology of the tumour revealed a
      cavernous haemangioma. Extracerebral location for a cavernous haemangioma is
      rare. An interpeduncular cavernous haemangioma has never been reported earlier in
      literature. The clinical and radiological features are discussed and relevant
      literature is briefly reviewed.

PMID- 11832623
TI  - Fallot's tetralogy presenting with variceal bleed.
AB  - The erythrocytosis of Fallot's tetralogy may lead to spontaneous thrombosis at
      any site, but splenic vein thrombosis and variceal bleed is rarely a presentation
      of Fallot's tetralogy. A case of a 48 years old female with undiagnosed Fallot's
      tetralogy, presenting with variceal bleed due to splenic vein thrombosis, is
      reported. It is also interesting to note that the patient survived till this age
      without any medical or surgical treatment.

PMID- 11832624
TI  - Anaesthetic management of splenectomy in Evan's syndrome during pregnancy with
      pregnancy induced hypertension.
AB  - The management of idiopathic thrombocytopenic purpura (ITP) during pregnancy,
      especially with ongoing bleeding diathesis, has not been highlighted sufficiently
      in the literature. Aortocaval compression and reduction in uteroplacental
      circulation resulting in foetal hypoxia and acidosis, Mendelson's syndrome due to
      gravid uterus, trauma to airway with resultant haemorrhage and aspiration into
      lungs, compromised airway due to short neck, anasarca and heavy breast,
      limitation in using invasive monitoring and regional anaesthesia and uncontrolled
      bleeding leading to placental hypoperfusion and foetal hypoxia are some of the
      important risks. In the present case report, anaesthetic management for
      splenectomy during pregnancy complicated with pregnancy induced hypertension and
      bleeding diathesis secondary to ITP is described with reference to above risks.

PMID- 11832625
TI  - ICH Harmonised Tripartite Guideline: Guideline for Good Clinical Practice.

PMID- 11832626
TI  - Cleidocranial dysplasia.

PMID- 11832627
TI  - Clear cell sarcoma of the kidney.

PMID- 11832628
TI  - Bilateral congenital capitate-hamate fusion.

PMID- 11832629
TI  - Peer review -- process, perspectives and the path ahead.

PMID- 11832630
TI  - End-tidal carbon dioxide monitoring in pediatrics - clinical applications.
AB  - End-tidal CO2 monitoring is an exciting non-invasive technology that is more
      commonly used in the emergency department, intensive care unit and in the
      prehospital setting. Its main use has been in verifying endotracheal tube
      position, during mechanical ventilation and cardiopulmonary resuscitation, but it
      is being studied and used for other purposes as well. The new American Heart
      Association guidelines require secondary confirmation of proper tube placement in
      all patients by exhaled CO2 immediately after intubation and during transport.
      This article covers the clinical applications of end-tidal CO2 monitoring with
      special reference to the paediatric patient.

PMID- 11832631
TI  - Anaesthesia management for subtotal thyroidectomy in a case of multinodular
      goitre with retrosternal extension and superior vena caval syndrome.

PMID- 11832632
TI  - Tuberculosis associated haemophagocytic syndrome.

PMID- 11832633
TI  - Keratinous micro cysts in viral interstitial pneumonitis.

PMID- 11832634
TI  - The history of biochemistry in India.

PMID- 11832636
TI  - A few steps towards responsible authorship (and editorship).

PMID- 11832635
TI  - The story of Wilma Rudolph.

PMID- 11832637
TI  - Surgical pathology of cystic lesions of the mediastinum.
AB  - BACKGROUND: Mediastinal cysts are uncommonly encountered in a pathologist's
      experience. AIMS: To study the incidence, location, clinical presentation and
      histologic subtypes of cysts in the mediastinum. MATERIALS AND METHODS: Cystic
      lesions of the mediastinum, surgically excised over a period of 22 years were
      studied after retrieval of relevant clinical data and slides. RESULTS: Thirty
      nine mediastinal cysts were encountered in the study period. Most of the patients
      (81.5 %) were symptomatic. Histologically, foregut cysts (19 cases, 50 %) were
      the most common followed by teratomatous cysts (ten cases, 26.3 %) and thymic
      cysts (four cases, 10.5 %). Bronchogenic cysts represented 63 % of the fore-gut
      cysts. Unusual lesions in the form of cystic mediastinal tuberculous
      lymphadenitis and cystic schwannoma were seen in three patients. CONCLUSIONS:
      Despite varied location and histology, clinical presentation of mediastinal cysts
      are similar. Surgical intervention is the preferred line of management.

PMID- 11832638
TI  - In-vitro antimalarial activity of azithromycin against chloroquine sensitive and
      chloroquine resistant Plasmodium falciparum.
AB  - BACKGROUND: [corrected] The spread of drug resistance in Plasmodium falciparum
      has made the situation essential to look into new effective therapeutic agents
      like antibiotics. Azithromycin is a potential, chemotherapeutic agent which
      possesses antimalarial activity and favourable pharmacokinetic properties. It is
      an azalide microbiocide derived semi-synthetically from macrolide erythromycin.
      Like other antibiotics, the azalide azithromycin has ability to inhibit protein
      synthesis on 70S ribosomes. SETTINGS: Experimental study. SUBJECTS AND METHODS:
      The parasiticidal profile was studied in five chloroquine sensitive and five
      chloroquine resistant P. falciparum isolates obtained from various places of
      India. The antimalarial activity was evaluated in P. falciparum schizont
      maturation by short term culture for 24 hours and by exposing the parasites to
      the drug for 96 hours. Parasites synchronized at ring stage were put for culture
      with various concentrations of azithromycin dihydrate (0.01-40 micro/ml).
      RESULTS: At highest concentration (40 micro/ml), parasite growth was inhibited
      totally in all 10 isolates. Antimalarial activity at 96 hours was greater than at
      24 hours in both chloroquine sensitive and resistant parasites, which may
      indicate that the inhibition of parasite growth may occur at clinically
      achievable concentration of the drug when parasites were exposed for several
      asexual cycles. CONCLUSION: Azithromycin shows a potential for eventual use alone
      or in combination in the treatment of chloroquine sensitive and resistant P.
      falciparum malaria.

PMID- 11832639
TI  - Thyroid nodules in Graves' disease: implications in an endemically iodine
      deficient area.
AB  - BACKGROUND AND AIM: The presence of thyroid nodules with Graves' disease raises
      concern about co-existent thyroid malignancy. The objective of this study is to
      evaluate the risk of thyroid carcinoma and the need for surgical intervention in,
      patients with Graves' disease with co-existent nodules in an endemically iodine
      deficient area (IDA). SUBJECTS AND METHODS: Retrospective study of 130 surgically
      managed patients of Graves' disease (1990-1999). Out of these 35 (26.9%) cases
      had palpable nodules. No patient had history of previous head and neck
      irradiation or radioiodine therapy. The clinico-pathological findings and follow
      up of these cases were noted. RESULTS: Mean age of patients with nodules was 40.2
      +/- 9.5 years and male to female ratio was 1:2.2. The overall incidence of
      thyroid carcinoma in Graves' disease was 6.2% (8/130 cases), while the incidence,
      in cases having nodule with Graves' disease was 17.1% (6/35 cases). The median
      age of patients with carcinoma was 45 years (5 women and 1 man). Besides
      laboratory investigations for hyperthyroidism, preoperative investigations
      included fine needle aspiration cytology (FNAC) and thyroid scintigraphy in 29
      and 25 cases respectively. Incidence of malignancy in palpable cold nodules was
      20%. FNAC could not predict malignancy with certainty in any of these cases. Five
      patients had papillary thyroid carcinoma while one had follicular carcinoma.
      Median tumour diameter was 10 mm. Tumour was multi-centric in two cases while one
      case had metastases to cervical lymph node. In follow-up (median =5.5 years) one
      patient died of unrelated cause, while rest are alive with no evidence of
      disease. CONCLUSIONS: Nodules are frequently associated with Graves' disease in
      IDA. Incidence of carcinoma is high in palpable cold nodule. We recommend early
      thyroidectomy in these cases.

PMID- 11832640
TI  - Atypical manifestations of typhoid fever.
AB  - BACKGROUND: High fever, toxaemia, constipation during first week of fever,
      complicated by encephalopathy and perforation during third week of fever are the
      typical manifestations of typhoid fever. However, the classical presentation of
      typhoid fever has considerably changed now. AIM: To study atypical presentations
      of typhoid fever. SETTING: A teaching unit of a hospital in South India METHOD:
      All culture-positive adult patients of typhoid fever admitted over a period of
      seven years were studied RESULTS: Thirty-two adult patients were admitted.
      Fifteen (46.9%) patients presented with atypical manifestations. Atypical
      manifestations observed were burning micturition with normal urine examination
      (n= 5, 15.6%) diarrhoea in first week (6.2%), encephalopathy in first week
      (3.1%), isolated hepatomegaly (6.2%), pneumonitis (3.1%) and bone marrow
      depression (6.2%). Out of 32 Salmonella typhi culture positive patients, 10
      (31.3%) patients had multidrug resistant (MDR) strain. Patients with MDR strains
      had atypical manifestations (5/10=50%) not significantly more often than patients
      having multidrug sensitive strains (10/22=45.5%) (Z <2). All patients responded
      to treatment. CONCLUSION: It appears atypical manifestations do not necessarily
      mean a worse prognosis in typhoid fever. Patients having high fever presenting
      with pneumonia, early encephalopathy, early diarrhoea or bone marrow depression
      in a typhoid endemic area, should be suspected for this disease.

PMID- 11832641
TI  - The Antley-Bixler syndrome: two new cases.
AB  - The Antley-Bixler syndrome is a rare multiple congenital anomaly with a high
      mortality rate. The characteristic manifestations include craniosynostosis,
      radiohumeral synostosis, midface hypoplasia, joint contractures and
      arachnodactyly. We report two new cases of this syndrome and address the
      diagnostic features, associated malformations, inheritance patterns, prenatal
      findings, and briefly review the literature.

PMID- 11832642
TI  - An unusual periaqueductal glioma: A short report.
AB  - A rare case of periaqueductal glioma with an unusual radiological picture is
      presented. A forty-five year old male presented with progressive bilateral third
      and eighth nerve paresis. Magnetic resonance imaging (MRI) revealed a diffuse
      periaqueductal tumour with sparing of aqueduct and no hydrocephalus. MRI is a
      useful adjunct in such a situation for contemplating appropriate modality of
      treatment.

PMID- 11832643
TI  - Peri-operative management of patients for video assisted thoracoscopic thymectomy
      in myasthenia gravis.
AB  - Three patients of myasthenia gravis, who under went video-assisted thoracoscopic
      surgery (VATS) were given general anaesthesia by propofol infusion and muscle
      relaxation by atracurium infusion. Isoflurane was added to control depth of
      anaesthesia on the basis of haemodynamic changes during surgery. One lung
      ventilation (OLV) was achieved by placement of Carlens left sided double lumen
      bronchocatheter. Right-sided surgical approach was used to perform thymectomy.
      Contrary to claimed short duration of surgery, in first patient, OLV lasted for
      10 hours 30 minutes and patient developed re-expansion pulmonary oedema. OLV in
      second and third patient was for six hours thirty minutes and three hours 45
      minutes respectively. Morning dose of pyridostigmine was omitted and atracurium
      (0.1 mg/kg) was found to be satisfactory for intubation and relaxation was
      maintained with atracurium infusion to get desired monitored effect. We could not
      extubate our patients due to longer duration of surgery and the sequelae there
      off. Post-operative elective ventilation and spontaneous weaning off the
      atracurium effect was thus preferred.

PMID- 11832644
TI  - Unilateral central retinal artery occlusion following intravenous streptokinase.
AB  - A 38-year-old male with acute myocardial infraction who had received
      streptokinase presented with acute painless diminution of vision in the left eye.
      Examination revealed features of central retinal artery occlusion on the left
      side with vision of perception of light. Treatment in the form of systemic and
      local intraocular pressure lowering agents, retrobulbar xanthinol nicotinate and
      systemic injection of B-complex resulted in improvement of vision to counting
      fingers up to one meter. In this case thrombolytic therapy itself led to embolism
      into the left central retinal artery resulting in its occlusion and eventually
      optic atrophy and blindness.

PMID- 11832645
TI  - ICH harmonised tripartite guideline: guideline for good clinical practice. 8.
      Essential documents for the conduct of a clinical trial.

PMID- 11832646
TI  - Molluscum contagiosum and Job's syndrome.

PMID- 11832647
TI  - Squamous cell carcinoma of breast.

PMID- 11832648
TI  - Mondini defect.

PMID- 11832649
TI  - Molecular diagnosis in haemophilia A.
AB  - Haemophilia A is the commonest cause of X-linked inherited bleeding disorder. Due
      to inadequate medical facility for management of the disease, the DNA based
      genetic diagnosis has assumed great importance. Ideally, the direct detection of
      mutations is the most accurate and reliable approach for carrier detection and
      prenatal diagnosis. However, mutation detection is possible only in limited
      number of cases. In majority of haemophiliacs, no common mutation is easily
      identifiable. The limitation has been over come by the use of linkage-based
      analysis using polymorphic DNA markers in the factor VIII gene. Some of these
      markers can be identified by restriction enzymes and are called RFLP markers.
      Other markers are a class of short tandem repeats sequences which result in
      differences in the number of CA repeats in different individuals. The combined
      use of these markers has made it possible to identify carriers and provide
      prenatal diagnosis in upto 95% of families having affected individuals.
      Therefore, the recurrence of the disease can be prevented to a great extent in
      the haemophilia A affected families.

PMID- 11832650
TI  - Heterotopic uterine cartilage.

PMID- 11832651
TI  - Amphotericin B induced ventricular arrhythmia and its relation to central venous
      line.

PMID- 11832652
TI  - History of preventive and social medicine in India.

PMID- 11832654
TI  - Role of p38(MAPK) in cell volume regulation of perfused rat liver.
AB  - In perfused rat liver, hypoosmotic exposure (225 mosmol/L) leads to a volume
      regulatory decrease by release of K(+), Cl(-) and HCO(3)(-) through Ba(2+)-, DIDS
      and quinidine-sensitive ion channels. The underlying signal transduction
      mechanisms, however, are unknown. As hypoosmotic hepatocyte swelling leads to a
      rapid activation of extracellular signal regulated kinases (Erks) and of
      p38(MAPK), the role of mitogen-activated protein kinases (MAPK) and PI-3-kinase
      in mediating the RVD in perfused rat liver was studied. The presence of the MEK
      inhibitor PD 098 059, which blocks the hypoosmotic activation of Erks, had no
      effect on the extent and time course of cell volume regulatory K(+) efflux.
      However, inhibitors of p38(MAPK) such as SB 203 580 and PD 169 316, but not their
      inactive analogue SB 202 474, significantly delayed and diminished the volume
      regulatory K(+) efflux. Accordingly, in presence of these p38(MAPK) inhibitors,
      the hepatocytes remained in a more swollen state after completion of RVD.
      Inhibition of hypoosmotic Erk activation by pertussis or cholera toxin, erbstatin
      or genistein had no effect on RVD by hypoosmolarity. Likewise, neither inhibition
      of PI-3-kinase by wortmannin or LY 294 002 nor inhibition of S 6 phosphorylation
      by rapamycin nor protein kinase inhibition by H-7, H-89 or KT 5823 led to a
      significant change of RVD upon hypoosmolarity. The amount and time course of K(+)
      release by oxidative stress upon addition of t-BOOH or H(2)O(2) remained
      unaffected by inhibition of p38(MAPK) by SB 203 580, suggesting a specific
      inhibition of RVD-dependent K(+) release by this inhibitor. The findings suggest
      that swelling-induced activation of p38(MAPK), but not of Erks and PI-3-kinase,
      is involved in RVD in liver, whereas p38(MAPK) is apparently not involved in the
      net K(+) release induced by oxidative stress.

PMID- 11832655
TI  - Swelling-induced K(+) fluxes in vascular smooth muscle cells are mediated by
      charybdotoxin-sensitive K(+) channels.
AB  - This study examines the relative contributions of K-Cl cotransport and K(+)
      channels to swelling-induced K(+) fluxes in vascular smooth muscle cells (VSMC).
      DIOA known as a potent inhibitor of erythrocyte K-Cl cotransport exerts diverse
      side-effects on VSMC and can not be used to analyze the role of this carrier in
      swelling-induced K(+) fluxes. Other inhibitors of K-Cl cotransport (furosemide,
      okadaic acid and calyculin A) did not affect K(+) fluxes in VSMC triggered by
      swelling. Swelling-induced K(+) fluxes in VSMC were also not affected by K(+)
      channel blockers such as TEA, glibenclamide and apamin, but were blocked by
      Ba(2+) and charybdotoxin (ChTX), a potent inhibitor of Ca(2+)- and voltage-gated
      K(+) channels. Swelling-induced K(+) influx in VSMC was diminished in Ca(2+)-free
      medium and in cells loaded with Ca(2+) chelator BAPTA, but was not accompanied by
      detectable elevation of [Ca(2+)](i). In contrast to Ca(2+)-induced
      hyperpolarization of erythrocytes triggered by activation of intermediate
      conductance Ca(2+)-gated K(+) channels (IK(Ca)), neither clotrimazole nor
      calmodulin antagonists (R24571, trifluoroperazine, fluphenazine) affected
      swelling-induced K(+) influx in VSMC. In conclusion, K(+) fluxes triggered in
      swollen VSMC are mediated by Ba(2+)- and ChTX-sensitive K(+) channels. These
      channels are distinct from IK(Ca) expressed in erythrocytes. Their molecular
      origin and systems involved in the swelling-induced Ca(2+)(i)-independent signal
      transduction pathway need further investigation.

PMID- 11832656
TI  - External Cl(-)-dependent formation of watery vacuoles by long-term hypotonic
      shock in 3T3-L1 cells.
AB  - Osmotic shock transiently induces a volume change in the cells, followed by a
      restoration of the cell volume due to intracellular water regulation. Effect of
      long-term osmotic shock on the water regulation is not completely understood.
      Vacuole formation by long-term osmotic shock was investigated to clarify the
      water exclusion mechanism from cytoplasm into intracellular vacuoles in 3T3-L1
      cells. Incubation of cells in hypotonic solution reversibly induced the vacuole
      formation. Staining of vacuoles with fluorescent dyes revealed that vacuoles were
      derived from endoplasmic reticulum and Golgi apparatus but not lysosomes.
      Membrane-impermeable fluorescent dyes were taken up into some vacuoles from
      cytoplasm and extracellular solution, suggesting that some vacuoles exhibit the
      dynamic changes for the connection of plasma membrane, and that transporter for
      membrane-impermeable dyes might be active in some vacuole membranes. External Cl(
      ), but not Na(+), was required for vacuole formation. DPC suppressed the vacuole
      formation and increased cell height, and further incubation with DPC increased
      the number of dead cells. Bumetanide, dimethylamiloride, and HgCl(2) did not
      suppress the hypotonic stress-induced formation of water vacuoles. These findings
      suggest that 3T3-L1 cells regulate the intracellular water content through the
      DPC-sensitive external Cl(-)-dependent vacuole formation during long-term osmotic
      stress.

PMID- 11832657
TI  - Gene expression profiles of CLC chloride channels in animal models with different
      cardiovascular diseases.
AB  - Here for the first time we investigated the potential involvement of the CLC
      chloride channel family at the transcriptional level in different cardiovascular
      diseases. Northern blot and semiquantitative RT-PCR analyses were used to study
      the gene expression profiles of all CLC genes present in the heart and kidney;
      namely, CLC-2, CLC-3, CLC-4, CLC-5, CLC-6, CLC-7, CLC-K1, and CLC-K2. Rat models
      with distinctive cardiovascular diseases were studied: These included
      spontaneously hypertensive rats, nutritionally- and surgically-induced
      hypertensive rats with cardiac hypertrophy, as well as rats suffering from
      chronic heart failure due to myocardial infarction. The present data show that it
      was not possible to detect apparent differences in the CLC mRNA expression
      between the hearts and kidneys of diseased and control animals. Our data strongly
      suggest that altered transcript regulation of CLC chloride channels does not
      contribute to the cardiac and renal pathology in the examined cardiovascular
      diseases.

PMID- 11832658
TI  - Suppression of cell division by pKi-67 antisense-RNA and recombinant protein.
AB  - The human antigen defined by the monoclonal antibody Ki-67 (pKi-67) is a human
      nuclear protein strongly associated with cell proliferation and found in all
      tissues studied. It is widely used as a marker of proliferating cells, yet its
      function is unknown. To investigate its function we suppressed pKi-67 expression
      by antisense RNA and overexpressed a partial structure of pKi-67 in HeLa cells. A
      BrdU-incorporation assay showed a significant decrease in DNA synthesis after
      antisense inhibition. Cell cycle analysis indicated a higher proportion of cells
      in G1 phase and a lower proportion of cells in S phase while the number of G(2)/M
      phase cells remained constant. Overexpression of a recombinant protein encoding
      three of the repetitive elements from exon 13 of pKi-67 had a similar effect to
      that obtained by antisense inhibition. The similarity of the effect of expressing
      'Ki-67 repeats' and pKi-67 antisense RNA could be explained by a negative effect
      on the folding of the endogenous protein in the endoplasmatic reticulum.
      Furthermore excessive self-association of pKi-67 via the repeat structure could
      inhibit its nuclear transport, preventing it from getting to its presumptive site
      of action. We conclude that the Ki-67 protein has an important role in the
      regulation of the cell cycle, which is mediated in part by its repetitive
      elements.

PMID- 11832659
TI  - Distinct guanine nucleotide binding protein alpha-subunit receptor coupling in GH
      cell lines: effects of bromocriptine and hormones on effector enzyme modulation.
AB  - The purpose of the present study was to elucidate how the dopamine agonist
      bromocriptine affected receptor-effector systems in GH cells by measuring
      adenylate cyclase (AC) and phospholipase C (PL-C) modulation in cell membrane
      preparations. To perturb the interaction between the receptor and G-protein,
      polyclonal antibodies reacting with the predicted C-terminal amino acid sequence
      of G-protein alpha-subunits were used. The effect of bromocriptine on
      secretagogue elicited prolactin (PRL) secretion from whole cells was also
      monitored. Bromocriptine inhibited the basal secretion of PRL in a dose dependent
      manner, and completely abolished both the thyroliberin (TRH) and the vasoactive
      intestinal peptide (VIP) stimulated PRL secretion in GH(3) cells. Maximal
      inhibitory effect on PRL egress elicited by both hormones was obtained at 10-50
      microM of bromocriptine. Messenger RNAs for both the short and long form of the
      D(2) receptor (D(2)R) were demonstrated in all three GH cell lines using the RT
      PCR technique, advocating that D(2)Rs are coupled to distinct G-proteins and,
      thus, probably being responsible for the observed effects of bromocriptine in
      these cell lines. Basal AC activity, as measured in membrane preparations of
      GH(3) cells, remained unaffected by bromocriptine treatment (10 microM), while
      TRH and VIP stimulated AC activities (175% and 350% of control values,
      respectively) were partially inhibited (by some 50%). This inhibitory effect of
      bromocriptine was completely and specifically abolished in the presence of an
      antiserum against G(i2)alpha. Basal PL-C activity was also unaffected by
      bromocriptine, while TRH stimulated PL-C activity (350% of control value) was
      inhibited by bromocriptine (10 microM) by approximately 50%. Immunoblocking of
      G(q/11)alpha, however, reduced the stimulatory effect of TRH on PL-C activation
      by some 65%, while an antiserum against G(o)alpha partly counteracted the
      inhibitory effect of bromocriptine (10 microM) on TRH stimulated PL-C activity.
      Thus, TRH dependent AC stimulation was counteracted by bromocriptine via G(i2).
      TRH activation of PL-C occurs via G(q/11), while inhibition by bromocriptine
      appears to involve G(o). These mechanisms probably account for the major part of
      the actions of bromocriptine, however, other not yet recognised intermediates may
      be involved.

PMID- 11832660
TI  - Are you ready for another paradigm shift?

PMID- 11832661
TI  - The gift: introduction to Masters of Heart Failure Series.

PMID- 11832662
TI  - Nuggets, pearls, and vignettes of master heart failure clinicians. Part 1--the
      medical history.

PMID- 11832663
TI  - Role of echocardiography in the assessment of left ventricular thrombus embolic
      potential after anterior acute myocardial infarction.
AB  - The contribution of cardiac ultrasound in assessment of the embolic potential of
      left ventricular thrombi after anterior acute myocardial infarction was verified
      in a prospective study of serial echocardiograms (mean, 18.9 examinations per
      patient) obtained over a long-term period (1-72 months; mean, 38+/-12). The study
      population comprised 222 patients (162 men; age, 64+/-11 years) with a first
      anterior acute myocardial infarction, treated with thrombolysis (group A) or
      receiving no antithrombolic therapy (group B). Embolism occurred in a total of 12
      patients (11 with a left ventricular thrombus; p<0.005) and was more frequent in
      group B (10 patients; p<0.04). Predictors of embolism were the absence of
      thrombolysis, detection of a left ventricular thrombus, protrusion or mobility of
      the thrombus, and morphologic changes in the thrombus over time. Patients in
      group A had a lower incidence of each of these predictors, and a higher thrombus
      resolution rate. An appropriate echocardiographic protocol is crucial to
      assessment of the embolic potential of left ventricular thrombi after anterior
      acute myocardial infarction and may help to identify candidates for aggressive
      antithrombotic therapy (c)2001 CHF, Inc.

PMID- 11832664
TI  - Severe hypocalcemia: a rare cause of reversible heart failure.
AB  - Despite the crucial role of calcium in myocardial contractility, hypocalcemia has
      been rarely reported as a cause of heart failure. In this article, the authors
      describe a case of severe hypocalcemia caused by idiopathic hypoparathyroidism
      and worsened by concomitant hypomagnesemia. The patient presented with congestive
      heart failure that improved dramatically with amelioration of plasma calcium
      levels. This case and other similar cases in the literature revealed that
      hypocalcemic heart failure is reversible. Measurement of plasma calcium should be
      included in the initial work-up of all patients with heart failure, and plasma
      magnesium must also be checked and corrected if hypocalcemia is demonstrated.
      (c)2001 CHF, Inc.

PMID- 11832665
TI  - Left atrial overload can be used to estimate mitral regurgitant volume.
AB  - This study was conducted to assess the accuracy of the estimated mitral
      regurgitant volume using both the left atrial filling volume and the systolic
      component of pulmonary vein flow expressed as the percent of its total. Since
      mitral regurgitation fills the left atrial chamber, the variation in atrial
      volume during ventricular systole has been proposed as a means to evaluate the
      severity of regurgitation. Although the correlation with invasive grading of
      mitral regurgitation is good, there is an unacceptable overlap among grades
      caused by the absence of information concerning pulmonary vein flow, which enters
      the left atrium while regurgitation occurs. The Doppler regurgitant volume, or Dp
      RVol (mitral stroke volume minus aortic stroke volume) was quantified in 74
      patients with any degree and etiology of mitral regurgitation. Atrial volumes
      were measured from the four-chamber apical view (biplane area-length method). The
      systolic time-velocity integral of pulmonary vein flow was expressed as the
      percent of the total (PVs%) (systolic-diastolic) time-velocity integral. These
      parameters were subjected to multivariate analysis and a regression equation was
      obtained. The equation was subsequently applied to a group of 31 patients without
      mitral regurgitation, as evaluated by color Doppler or continuous-wave Doppler
      and to the overall population (105 patients) in order to estimate the mitral
      regurgitant volume. In 74 patients with mitral regurgitation, the Doppler
      regurgitant volume was univariately correlated with the left atrial filling
      volume (r= 0.74; p<0.0001) and the systolic pulmonary vein velocity integral
      expressed as the percent of the total (r=0.67; p<0.0001). In multiple regression
      analysis, the combination of atrial filling and the pulmonary vein velocity
      integral provided the more accurate estimation of the regurgitant volume
      (R2=0.84; standard error of the estimate [SEE], 13.9 mL; p<0.0001; Dp-RVol equals
      7.84+[1.08*left atrial filling volume] 2 [0.839*PVs%]). In 31 patients with no
      mitral regurgitation detected by color Doppler or continuous wave Doppler the
      estimated regurgitant volume was 4.3+/-6.6 mL. In the overall population the
      estimated regurgitant volume and the Doppler regurgitant volume correlated well
      with each other (R2=0.85; SEE, 11.5 mL; p<0.0001). The equation was 100%
      sensitive and 98% specific in detecting a regurgitant volume higher than 55 mL.
      The combination of the atrial filling volume and the systolic pulmonary vein time
      velocity integral expressed as the percent of the total allows reliable
      estimation of the regurgitant volume in patients with mitral regurgitation.
      (c)2001 CHF, Inc.

PMID- 11832666
TI  - Pharmacotherapy in congestive heart failure. Prematurely terminated clinical
      trials and their application to cardiovascular medicine.
AB  - Controlled clinical trials in cardiovascular disease remain the cornerstone of
      field-specific therapeutic advances. Since the introduction of the concept of
      controlled clinical trials, there has been considerable fine-tuning of the
      design, conduct, and analysis of such studies. A growing awareness of ethical
      issues emerging from such trials has led to increased public and investigator
      scrutiny and the routine requirement for both interim data analysis and full
      conflict-of-interest disclosure. A benefit of such interim analyses is that
      either an entire clinical trial or a specific treatment limb can be stopped if
      the observed findings warrant early termination. For example, highly positive
      findings, as were noted in the HOPE Study (Heart Outcomes Prevention Evaluation),
      led to its closure after 4.5 years of treatment, which was 1 year earlier than
      anticipated. Also, the doxazosin treatment limb of ALLHAT (Antihypertensive and
      Lipid-Lowering Treatment to Prevent Heart Attack Trial) and the amlodipine
      treatment limb of AASK (African American Study of Kidney Disease and
      Hypertension) were stopped early, because of negative findings in one of their
      treatment limbs. Finally, economic considerations can enter into the decision to
      close a study early, as was the case in the CONVINCE (Controlled-Onset Verapamil
      Investigation of Cardiovascular Endpoints) trial. Most such decisions rely
      heavily on information obtained from independent data and safety monitoring
      boards. Such boards ensure patient safety by providing an unbiased, ongoing
      review of data, which would otherwise be unavailable until a study's completion.
      Early termination of a clinical trial can have important clinical and economic
      implications and, in particular, can substantially redirect the pattern of
      clinical practice. (c)2001 CHF, Inc.

PMID- 11832667
TI  - Frontiers in congestive heart failure: predictors of isotonic exercise in
      patients with heart failure.

PMID- 11832668
TI  - Frontiers in congestive heart failure: the role of the implantable cardioverter
      defibrillator for prevention of sudden cardiac death.

PMID- 11832669
TI  - Difficult cases in heart failure. Novel diagnostic markers in heart failure: an
      emerging paradigm shift?
AB  - The differential diagnosis of dyspnea can be overwhelming in the presence of
      competing diseases. The recent advent of the peptide marker brain natriuretic
      peptide has ushered in an era of refined diagnostic capability in heart failure.
      We present a clinical scenario to illustrate the usefulness of this new biomarker
      assay in directing appropriate therapy for heart failure. (c)2001 CHF, Inc.

PMID- 11832670
TI  - Diet: How Important Is It in the Treatment of Hypercholesterolemia?

PMID- 11832671
TI  - A Comparison of NCEP and Absolute Risk Stratification Methods for Lipid-Lowering
      Therapy in Middle-Aged Adults: The ARIC Study. The ARIC Investigators.
AB  - Lipid-lowering therapy has been shown to reduce cardiovascular disease risk in
      individuals with low-density lipoprotein cholesterol (LDL-C) levels of at or
      above 130 mg/dL. Several methods have been developed for identifying those at
      highest risk for treatment. The objective was to compare the 1993 National
      Cholesterol Education Program guidelines to absolute risk assessment methods
      similar to those used by recently developed European and British cholesterol
      treatment guidelines. The design and setting was a population-based, prospective
      cohort study in four US communities. Among Atherosclerosis Risk in the
      Communities study participants aged 45-64 years followed for a mean of 7 years,
      7314 women and 5762 men were included who had no evidence of clinical
      cardiovascular disease and were not receiving lipid-lowering drug therapy at
      entry. Main outcome measures were number meeting criteria for treatment, number
      of cardiovascular events expected to be prevented with treatment, number needed
      to treat to prevent one cardiovascular event, and sensitivity of criteria for
      detecting cases for the entire cohort and for those at or above the LDL-C
      treatment threshold (within-group). The 1993 National Cholesterol Education
      Program guidelines identified 16% of participants for treatment: n=2112; events
      expected to be prevented=77; number needed to treat=27; sensitivity=0.31 (0.28
      0.35); sensitivity when LDL-C was greater-than-or-equal160 mg/dL=0.86. Use of a
      LDL-C treatment threshold of greater-than-or-equal130 mg/dL, a greater-than-or
      equal20% 10-year absolute risk cut-point (similar to European guidelines)
      identified 13% for treatment: n=1701; events expected to be prevented=66; number
      needed to treat=26; sensitivity=0.29 (0.25-0.32); sensitivity when LDL-C was >130
      mg/dL=0.43. A greater-than-or-equal15% risk cut-point (similar to British
      guidelines) identified 17% for treatment: n=2233; events expected to be
      prevented=82; number needed to treat=27; sensitivity=0.37 (0.33-0.40);
      sensitivity when LDL-C was greater-than-or-equal130 mg/dL=0.55. Modified National
      Cholesterol Education Program guidelines (LDL-C treatment threshold lowered from
      160 to 130 mg/dL for those with greater-than-or-equal2 risk factors) identified
      30% for treatment: n=3867; events expected to be prevented=120; number needed to
      treat=32; sensitivity=0.55 (0.52-0.59); sensitivity when LDL-C was 130
      mg/dL=0.83. A hybrid strategy using greater-than-or-equal15% risk, or 10% to 14%
      risk with a parental history of premature coronary heart disease or treated,
      controlled hypertension, identified 20% for treatment: n=2646; events expected to
      be prevented=97; number needed to treat=27; sensitivity=0.44 (0.40-0.47);
      sensitivity when LDL-C was greater-than-or-equal130 mg/dL=0.66. Depending on the
      priorities of a health care system, higher absolute cut-points can be used for
      allocating health care resources to those at the highest risk. However, fewer
      cardiovascular events will be prevented and fewer patients who later experience
      cardiovascular events will be offered treatment despite acceptable numbers needed
      to treat to prevent one cardiovascular disease event. A hybrid absolute risk
      strategy incorporating family history and treated hypertension information
      appears to be superior to absolute risk strategies that do not include this
      information. Copyright 2001 CHF, Inc.

PMID- 11832672
TI  - Dietary Counseling for High Blood Cholesterol in Families at Risk of Coronary
      Disease.
AB  - A positive family history of coronary heart disease alone confers an increased
      risk, which may be affected by untreated hypercholesterolemia. Dietary counseling
      is a first-line treatment approach. To determine whether nurse counseling can
      provide additional benefits over usual physician efforts to lower dietary fat in
      high-risk persons, 117 apparently healthy adult siblings of persons with
      premature coronary heart disease were counseled by a registered nurse using
      adapted national guidelines. Reductions in total fat, saturated fat, and
      cholesterol were significantly greater in the nurse group compared to those in
      the usual care group. Total fat intake decreased by 14 g in the nurse group,
      compared with an increase of 5 g in the usual care group (p=0.0001). Assignment
      to the nurse group was also a significant predictor of a greater reduction in the
      percentage of total fat calories (p=0.008). The authors conclude that a
      registered nurse may serve as a complement to usual care in efforts to lower
      dietary fat and cholesterol in high-risk families. (c)2001 CHF, Inc.

PMID- 11832673
TI  - Effects of Hatha Yoga Practice on the Health-Related Aspects of Physical Fitness.
AB  - Ten healthy, untrained volunteers (nine females and one male), ranging in age
      from 18-27 years, were studied to determine the effects of hatha yoga practice on
      the health-related aspects of physical fitness, including muscular strength and
      endurance, flexibility, cardiorespiratory fitness, body composition, and
      pulmonary function. Subjects were required to attend a minimum of two yoga
      classes per week for a total of 8 weeks. Each yoga session consisted of 10
      minutes of pranayamas (breath-control exercises), 15 minutes of dynamic warm-up
      exercises, 50 minutes of asanas (yoga postures), and 10 minutes of supine
      relaxation in savasana (corpse pose). The subjects were evaluated before and
      after the 8-week training program. Isokinetic muscular strength for elbow
      extension, elbow flexion, and knee extension increased by 31%, 19%, and 28%
      (p<0.05), respectively, whereas isometric muscular endurance for knee flexion
      increased 57% (p<0.01). Ankle flexibility, shoulder elevation, trunk extension,
      and trunk flexion increased by 13% (p<0.01), 155% (p<0.001), 188% (p<0.001), and
      14% (p<0.05), respectively. Absolute and relative maximal oxygen uptake increased
      by 7% and 6%, respectively (p<0.01). These findings indicate that regular hatha
      yoga practice can elicit improvements in the health-related aspects of physical
      fitness. (c)2001 CHF, Inc.

PMID- 11832674
TI  - Resolving the Coronary Artery Disease Epidemic Through Plant-Based Nutrition.
AB  - The world's advanced countries have easy access to plentiful high-fat food;
      ironically, it is this rich diet that produces atherosclerosis. In the world's
      poorer nations, many people subsist on a primarily plant-based diet, which is far
      healthier, especially in terms of heart disease. To treat coronary heart disease,
      a century of scientific investigation has produced a device-driven, risk factor
      oriented strategy. Nevertheless, many patients treated with this approach
      experience progressive disability and death. This strategy is a rear-guard
      defensive one. In contrast, compelling data from nutritional studies, population
      surveys, and interventional studies support the effectiveness of a plant-based
      diet and aggressive lipid lowering to arrest, prevent, and selectively reverse
      heart disease. In essence, this is an offensive strategy. The single biggest step
      toward adopting this strategy would be to have United States dietary guidelines
      support a plant-based diet. An expert committee purged of industrial and
      political influence is required to assure that science is the basis for dietary
      recommendations. (c)2001 CHF, Inc.

PMID- 11832675
TI  - An Association Between Varying Degrees of Hypothyroidism and Hypercholesterolemia
      in Women: The Thyroid-Cholesterol Connection.
AB  - Evidence of an association between subclinical hypothyroidism and cardiovascular
      disease is mounting. The impact of thyroid hormone on lipid levels is primarily
      mediated through triiodothyronine (T(3))-bound thyroid protein binding and
      activation of the promoter regions of the low-density lipoprotein receptor and 3
      hydroxy-3-methylglutaryl coenzyme A-reductase genes, leading to a reduction in
      serum cholesterol levels. Thus, the decreased T(3) seen in hypothyroidism may
      result in increased serum cholesterol. Although a clear correlation exists
      between overt hypothyroidism and clinically significant hypercholesterolemia,
      there is a logarithmic relationship between thyroid-stimulating hormone and
      cholesterol, and the effects of subclinical hypothyroidism on cardiovascular
      disease are under debate. However, current data suggest that normalizing even
      modest thyroid-stimulating hormone elevations may result in improvement in the
      lipid profile. (c)2001 CHF, Inc.

PMID- 11832676
TI  - Perspectives: A Practical Approach to the Dietary Treatment of
      Hypertriglyceridemia.
AB  - Reducing high plasma triglyceride (TG) levels is an important step in the
      treatment and prevention of coronary artery disease. The rise in plasma TGs seen
      after subjects consume low-fat, high-carbohydrate diets for a period of time may
      be due to the simple form of carbohydrate provided and/or prevention of weight
      loss in these studies. Ad libitum low-fat, high-carbohydrate intake often results
      in weight loss and decreases in plasma TGs. Replacing dietary carbohydrate with
      monounsaturated fat lowers serum TG levels and maintains serum high-density
      lipoprotein levels but fails to result in weight loss. Low-fat, high-complex
      carbohydrate intake reduces incidence rates of coronary artery disease. On the
      basis of the evidence, a low-fat, high-complex carbohydrate diet combined with
      limited alcohol and sugar intake is recommended for the treatment of
      hypertriglyceridemia. (c)2001 CHF, Inc.

PMID- 11832677
TI  - Did you know? Hormone Replacement Therapy and Heart Disease: Plausible Mechanisms
      and Observational Studies Yield to Hard Data.

PMID- 11832678
TI  - Detection of polyomavirus simian virus 40 tumor antigen DNA in AIDS-related
      systemic non-Hodgkin lymphoma.
AB  - Systemic non-Hodgkin lymphoma (S-NHL) is a common malignancy during HIV
      infection, and it is hypothesized that infectious agents may be involved in the
      etiology. Epstein-Barr virus DNA is found in <40% of patients with AIDS-related S
      NHL, suggesting that other oncogenic viruses, such as polyomaviruses, may play a
      role in pathogenesis. We analyzed AIDS-related S-NHL samples, NHL samples from
      HIV-negative patients, peripheral blood leukocytes from HIV-infected and 
      uninfected patients without NHL, and lymph nodes without tumors from HIV-infected
      patients. Specimens were examined by polymerase chain reaction analysis with use
      of primers specific for an N-terminal region of the oncoprotein large tumor
      antigen ( T-ag ) gene conserved among all three polyomaviruses (simian virus 40
      [SV40], JC virus, and BK virus). Polyomavirus T-ag DNA sequences, proven to be
      SV40-specific, were detected more frequently in AIDS-related S-NHL samples (6 of
      26) than in peripheral blood leukocytes from HIV-infected patients (6 of 26 vs. 0
      of 69; p =.0001), NHL samples from HIV-negative patients (6 of 26 vs. 0 of 10; p
      =.09), or lymph nodes (6 of 26 vs. 0 of 7; p =.16). Sequences of C-terminal T-ag
      DNA from SV40 were amplified from two AIDS-related S-NHL samples. Epstein-Barr
      virus DNA sequences were detected in 38% (10 of 26) AIDS-related S-NHL samples,
      50% (5 of 10) HIV-negative S-NHL samples, and 57% (4 of 7) lymph nodes. None of
      the S-NHL samples were positive for both Epstein-Barr virus DNA and SV40 DNA.
      Further studies of the possible role of SV40 in the pathogenesis of S-NHL are
      warranted.

PMID- 11832679
TI  - Evidence of nucleoside analogue reverse transcriptase inhibitor--associated
      genetic and structural defects of mitochondria in adipose tissue of HIV-infected
      patients.
AB  - To investigate if possible mitochondrial injury can be found in adipose tissue of
      nucleoside analogue reverse transcriptase inhibitor (NRTI)-treated patients,
      subcutaneous fat was taken from the buttocks of 24 HIV-positive patients and 8
      HIV-negative controls. The content of mitochondrial DNA (mtDNA) was quantified
      using a Southern blot technique. Fat biopsies were examined by electron
      microscopy and screened by restriction fragment length polymorphism analysis for
      the presence of the nt 8344 and 3243 mtDNA point mutations. Age, sex, and body
      mass index did not differ between the HIV-negative controls, the HIV-positive
      patients currently treated with NRTIs (NRTI group, n = 19), and the HIV-positive
      patients without NRTIs (no-NRTI group, n = 5). The mean mtDNA content was 44%
      lower in the NRTI group compared with the no-NRTI group ( p =.01) but did not
      differ between the control group and the no-NRTI group. When the HIV-infected
      patients were stratified to a group with clinical signs of lipoatrophy at the
      biopsy site (LA group, n = 11) and a group without lipoatrophy (no-LA group, n =
      13), the mean mtDNA content in the LA group was 39% lower than that in the no-LA
      group ( p =.02). No point mutations or deletions were observed. The adipocytes of
      patients with lipoatrophy contained multiple small lipid vacuoles, and the
      mitochondria harbored inclusions reminiscent of mtDNA cytopathies. mtDNA
      depletion and ultrastructural abnormalities of adipocytes suggest a link between
      mitochondrial damage, the use of NRTIs, and lipoatrophy in HIV-infected patients.

PMID- 11832680
TI  - Changes in CCR5 and CXCR4 expression and beta-chemokine production in HIV-1
      infected patients treated with highly active antiretroviral therapy.
AB  - The effect of highly active antiretroviral therapy (HAART) on the expression of
      CCR5 and CXCR4 HIV coreceptors and the production of the beta-chemokines
      regulated upon activation, normal T-cell expressed and secreted (RANTES),
      macrophage inflammatory protein (MIP)-1alpha, and MIP-1beta has been investigated
      in 30 HIV-1-infected individuals during 12-36 months of therapy. CCR5 expression
      was increased in both CD4 + and CD8 + subsets, whereas CXCR4 expression was
      upregulated only in CD4 + cells. CCR5 levels normalized during 36 months of
      therapy and positively correlated with the levels of memory, CD95 +, and HLA-DR +
      T cells. In contrast, the frequency of CXCR4-expressing cells was not
      significantly modified by HAART, although a downregulation was observed early
      after starting treatment. CXCR4 levels were significantly associated with the
      frequencies of naive T cells and negatively correlated with plasma viral load,
      CD95, and HLA-DR expression. An increased production of both spontaneous and
      lectin-induced RANTES, MIP-1alpha, and MIP-1beta was found at baseline in HIV
      infected individuals. The spontaneous beta-chemokines production was not modified
      by 12 months of HAART, although a significant reduction was seen during the first
      months of therapy. A transient decrease of lectin-stimulated RANTES production
      was also observed, whereas the reduction of lectin-induced MIP-1alpha persisted
      for up to 12 months of therapy. In contrast, MIP-1beta secreted by
      phytohemagglutinin antigen-stimulated peripheral blood mononuclear cells
      progressively increased during HAART. In conclusion, our data indicate a
      normalization of CCR5 but not CXCR4 expression during suppressive therapy and
      changes in beta-chemokine production that may play a part in dictating the
      efficiency of viral infection and consequently the disease course.

PMID- 11832681
TI  - The impact of a partially effective HIV vaccine on a population of intravenous
      drug users in Bangkok, Thailand: a dynamic model.
AB  - Because of the variability of HIV, the first AIDS vaccine is likely to be only
      partially effective. There is some concern among scientists that a low-efficacy
      vaccine could worsen the HIV epidemic if vaccinated individuals increase their
      risk behavior under the false assumption of immunity. To address this concern, we
      constructed a dynamic compartmental model that simulated the course of the
      HIV/AIDS epidemic in a population of injection drug users in Bangkok, Thailand.
      The model calculated long-term HIV prevalence, number of AIDS cases, and total
      population size for two scenarios: vaccination program versus no vaccination
      program. We used sensitivity analyses to evaluate the impact of postvaccination
      risk behavior change on HIV prevalence. A 75% effective vaccine led to a 40-year
      HIV prevalence of 37% with vaccination and 50% without vaccination.
      Postvaccination behavior change had only a limited effect on the results with a
      75% effective vaccine but a significant effect with a 30% effective vaccine. If
      90% of low-risk individuals responded to a 30% effective vaccine with increased
      high-risk behavior, the benefit of vaccination disappeared. These results agree
      with analyses of the epidemic among gay men. If injection drug behavior is indeed
      modifiable, our findings have significant policy and planning implications.

PMID- 11832682
TI  - High prevalence of iron deficiency and anemia among female injection drug users
      with and without HIV infection.
AB  - INTRODUCTION: Anemia is associated with increased progression of disease and
      higher mortality during HIV infection. OBJECTIVE: To determine the prevalence of
      iron deficiency and iron deficiency anemia among female injection drug users
      (IDUs) with and without HIV infection. METHODS: Hemoglobin and plasma ferritin
      were measured in a cross-sectional study of a cohort of female IDUs followed in
      Baltimore, Maryland. RESULTS: Among 136 HIV-positive and 61 HIV-negative women,
      the prevalence of anemia was 44.1% and 26.2% ( p <.02), the prevalence of iron
      deficiency was 37.5% and 42.6% ( p =.49), and the prevalence of iron deficiency
      anemia was 20.6% and 14.7% ( p =.33), respectively. The overall prevalence of
      hepatitis C infection was 90.5%. Iron deficiency anemia accounted for 46.7% and
      56.1% of the anemia among HIV-positive and HIV-negative female IDUs. CONCLUSIONS:
      Iron deficiency accounts for about half of the anemia among female IDUS. Although
      iron supplementation is indicated for anemia patients, such treatment should be
      approached with caution in women coinfected with HIV and hepatitis C virus,
      because iron supplementation and overload have been associated with increased
      progression of HIV infection, worsening of hepatitis C virus infection, and
      higher mortality.

PMID- 11832683
TI  - Sustained suppression of HCV replication and inflammatory activity after
      interleukin-2 therapy in patients with HIV/hepatitis C virus coinfection.
AB  - OBJECTIVE: There is increasing evidence that coinfection of hepatitis C (HCV)
      with HIV is associated with accelerated progression of liver cirrhosis. The aim
      of this pilot study was to investigate toxicity and efficacy of interleukin-2 (IL
      2) for treatment of affected patients. DESIGN: Because low-dose, daily IL-2
      therapy is well tolerated and can elevate CD4 cell counts and improve immune
      functions, patients were treated with 1-2 million units (MU) IL-2 subcutaneously
      daily. METHODS: This pilot trial included 7 HIV/HCV-coinfected individuals.
      During therapy, clinical, virologic, and laboratory parameters were closely
      monitored. RESULTS: All patients responded to IL-2 therapy with either
      improvement of either CD4 cell counts or liver function test results. In 2
      patients, HCV-RNA in serum became negative 2 and 4 months, respectively, after
      cessation of therapy. HCV-RNA has remained undetectable in these 2 patients for
      18 and 24 months, respectively. Therapy was well tolerated and no grade III or IV
      toxicities were observed. CONCLUSIONS: Low-dose, daily IL-2 therapy can improve
      both CD4 cell counts and liver function test results in patients with HIV/HCV
      coinfection and may in some cases lead to sustained suppression of viremia of
      HCV.

PMID- 11832684
TI  - Clinical and biological evolution of HIV-1 seroconverters in Abidjan, Cote
      d'Ivoire, 1997-2000.
AB  - OBJECTIVE: To describe the clinical and biologic evolution of HIV-1 infection in
      Africa. METHODS: One hundred four HIV-1-infected individuals were identified
      prospectively from regular blood donors in Abidjan, Cote d'Ivoire. The date of
      seroconversion was estimated from results of sequential serologic tests. Biologic
      and clinical follow-up was performed every 6 months, starting as early as
      possible after seroconversion. Case management followed national guidelines.
      RESULTS: The median interval between estimated seroconversion and study inclusion
      was 9.7 months, and the median window of seroconversion was 2.8 months. At
      baseline, all but two patients were asymptomatic; the median CD4 + cell count was
      527/mm 3 (interquartile range [IR], 395-684), and the median plasma HIV RNA level
      was 4.6 log 10 copies/ml (IR, 3.8-4.9). The median follow-up was 23.9 months, and
      95% of the patients received primary prophylaxis with co-trimoxazole for
      opportunistic infections. Of the patients, 1 presented with wasting syndrome, 3
      developed tuberculosis, and 17 had a Centers for Disease Control and Prevention
      category B-defining event. The 3-year AIDS-free and symptom-free probabilities
      were 96.7% (95% confidence interval [CI], 87.0-99.2] and 79.3% (95% CI, 67.5
      87.2), respectively. During the first 3 years of follow-up, we observed that the
      median plasma viral load stabilized at >4 log 10 copies/ml and that the median
      CD4 + cell count declined by 20 to 25/mm 3 per year. CONCLUSION: These African
      seroconverters were moderately immunosuppressed. The median HIV RNA level was
      high and varied very little during the first 3 years, and there were few clinical
      events.

PMID- 11832685
TI  - Associations between dietary antioxidant intake and oxidative stress in HIV
      seropositive and HIV-seronegative men and women.
AB  - OBJECTIVE: To describe the relationship between dietary antioxidant intake and
      oxidative stress in clinically stable HIV-positive and HIV-negative adults.
      DESIGN: A cross-sectional study. METHODS: Average total daily dietary intakes of
      vitamin C, beta-carotene, alpha-tocopherol, selenium, and zinc from foods and
      nutritional supplements were estimated in noninstitutionalized individuals using
      the dietary history method. Plasma malondialdehyde (MDA) concentrations were
      measured by high-performance-liquid-chromatography (HPLC) whereas peripheral
      blood mononuclear cell glutathione (PBMC GSH) concentrations were determined
      spectrophotometrically by an enzymatic recycling assay. Data were analyzed in
      multiple linear regression models to investigate these relationships. RESULTS:
      Regression analysis revealed an inverse relationship between selenium intake and
      plasma MDA in a model that included the five dietary antioxidants ( R 2 = 0.25; p
      < .02) and with selenium only ( R 2 = 0.19; p < .01). Both models were adjusted
      for gender, smoking status, and HIV seropositivity. Antioxidant intake was not
      associated with PBMC GSH ( R 2 = 0.12, p = .36). In univariate analyses,
      oxidative stress did not significantly differ between clinically stable HIV
      positive and healthy HIV-negative study subjects. CONCLUSIONS: This is the first
      study to characterize the relationship between dietary antioxidant intake from
      food and supplements with oxidative stress. The results suggested dietary
      selenium intake was strongly and inversely associated with plasma MDA, but
      dietary antioxidant intakes were not related to PBMC GSH. This study also
      provides evidence that HIV infection was not specifically associated with
      oxidative stress among clinically stable individuals.

PMID- 11832686
TI  - Resistance to antiretroviral treatment in Gabon: need for implementation of
      guidelines on antiretroviral therapy use and HIV-1 drug resistance monitoring in
      developing countries.
AB  - The protease and reverse transcriptase (RT) genes were studied in antiretroviral
      (ARV)-experienced and drug-naive HIV-1-infected individuals in Libreville, Gabon.
      We have shown, although on a limited number of samples that in 58% (11/19) of the
      patients, with a mean of 17.7 months of ARV drug experience, major mutations
      inevitably inducing resistances to ARV drugs were present. Resistance was mainly
      observed to the NRTIs (nucleoside analogue RT inhibitors). This high prevalence
      may reflect inappropriate ARV drug use. In order to avoid the rapid emergence of
      resistant viruses on a large scale in the developing world, it is important that
      the infrastructures necessary to monitor ARV treatment are also rapidly
      implemented in these countries and that clinicans are trained in the appropriate
      use of ARV drugs. A continuous surveillance of the circulation of ARV drug
      resistant viruses must be organized to guide ARV treatment strategies and
      policies.

PMID- 11832687
TI  - Impact of selenium status on the pathogenesis of mycobacterial disease in HIV-1
      infected drug users during the era of highly active antiretroviral therapy.
AB  - The risk of mycobacterial disease is significantly increased in drug abusers as
      well as in immunocompromised HIV-1-infected individuals. The essential trace
      element selenium has an important function in maintaining immune processes and
      may, thus, have a critical role in clearance of mycobacteria. The impact of
      selenium status on the development of mycobacterial diseases in HIV-1
      seropositive drug users was investigated over a 2-year period (1999-2001). Twelve
      cases of mycobacterial disease (tuberculosis, 9; infection due to atypical
      Mycobacterium species, 3) occurred; these 12 cases were compared with 32 controls
      with no history of respiratory infections who were matched on age, sex, and HIV
      status. Significant risk for development of mycobacterial disease was associated
      with a CD4 cell count of <200/mm 3, malnutrition, and selenium levels of <or=135
      microg/L (patients with these levels were 13 times more likely to develop
      mycobacterial disease). Multivariate analyses controlling for antiretroviral
      treatment and CD4 cell count revealed that both body mass index and selenium
      level remained significant factors in the relative risk for developing
      mycobacterial disease (relative risk, 3; p =.015); these findings suggest that
      selenium status may have a profound impact on the pathogenesis of mycobacterial
      disease.

PMID- 11832688
TI  - Independent effects of reported sexually transmitted infections and sexual
      behavior on HIV-1 prevalence among adult women, men, and teenagers in rural
      Uganda.
AB  - OBJECTIVE: To assess whether sexually transmitted infections (STIs) and sexual
      behavior are independently associated with HIV-1 among adult women, men, and
      teenagers in rural Uganda. DESIGN: Cross-sectional survey. METHODS: All adults
      (13 years and older) residing in 18 communities were invited to participate. HIV
      status was determined from serum samples and data collected during confidential
      interview. Independent effects of risk factors for HIV were estimated using
      adjusted odds ratios (ORs) with 95% confidence intervals (CIs) from logistic
      regression. RESULTS: Women reporting genital ulcers in the last 12 months were
      over twice as likely to be HIV positive after adjustment for sociodemographic
      factors and number of lifetime sexual partners (OR, 2.5; 95% CI, 1.9-3.4).
      Equivalent associations were stronger for men (OR, 3.2; 95% CI, 2.2-4.7) but
      weaker for teenagers (OR, 2.0, 95% CI, 0.5-8.7). Number of lifetime sexual
      partners was associated ( p <.05) with HIV status for women, men, and teenagers
      independently of reported genital ulcers. Teenagers reporting casual partners
      were over four times ( p <.001), and men reporting condom use almost twice ( p
      <.001), as likely to be HIV positive. Neither history of genital discharge nor
      other measures of sexual behavior were independently related to HIV status.
      CONCLUSION: Reported STIs and sexual behavior are independently associated with
      HIV in rural Uganda. Community-based interventions to reduce HIV should target
      both and should include teenagers.

PMID- 11832689
TI  - Lymphoid neoplasms in HIV-positive individuals in India.
AB  - The HIV epidemic in the Asian subcontinent has a significant impact on India.
      Patients with AIDS have an increased risk of developing non-Hodgkin lymphoma
      (NHL). In this study, we have investigated the pattern of distribution of
      lymphoid neoplasms and also studied the Epstein-Barr virus (EBV)-association and
      p53 expression in 35 HIV-positive patients from India. The biopsy samples were
      studied for histology and for expression of CD20, CD3, CD15, CD30, light chains,
      CD138, bcl-6, epithelial membrane antigen, EBV-latent membrane protein-1, and p53
      protein. In situ hybridization was performed with digoxigenin-labeled anti-sense
      EBV-encoded nuclear RNA-1 (EBER-1) probe. Polymerase chain reaction (PCR) was
      performed on DNA extracted from paraffin sections for EBV-subtype analysis. The
      35 cases included 7 cases of Hodgkin disease (HD), 4 cases of plasmacytoma (PL),
      and 24 cases of NHL. Among the cases of NHL, 3 were Burkitt lymphoma (BL), 4 were
      diffuse large B-cell lymphoma (DLBL) of centroblastic type (CBL), 10 were DLBL of
      immunoblastic type (IBL), 4 were high-grade B-cell lymphoma (unspecified) and the
      rest were other subtypes. EBV-association was noted in all cases of HD, 2 of 3
      BL, and 3 of 10 IBL. PCR analysis of the EBNA-3C gene revealed amplimers
      corresponding to type A. A p53 protein overexpression was noted in 6 of 10 IBLs,
      1 of 3 BLs, 2 of 3 CBLs, and 5 of 7 cases of HD. This is the first reported study
      of lymphoid malignancies in HIV-positive individuals from India.

PMID- 11832690
TI  - Estimated global distribution and regional spread of HIV-1 genetic subtypes in
      the year 2000.
AB  - The objective of this study was to estimate the global distribution and regional
      spread of different HIV-1 genetic subtypes and circulating recombinant forms
      (CRFs) in the year 2000. These estimates were made based on data derived from
      global HIV/AIDS surveillance and molecular virology studies. HIV-1 incidence
      during the year 2000 was estimated in defined geographic regions, using a country
      specific model developed by WHO-UNAIDS. The proportion of new infections caused
      by different HIV-1 subtypes in the same geographic regions was estimated by
      experts from the WHO-UNAIDS Network for HIV Isolation and Characterization, based
      on results generated by HIV molecular epidemiology studies in 1998 to 2000. The
      absolute numbers and relative proportions of new infections due to different
      genetic subtypes of HIV-1 by different geographic regions were calculated using
      these two sets of estimated data. The results of the study demonstrated that the
      epidemiology of HIV-1 subtypes and CRFs is characterized by their differential
      distribution and varying significance as a driving cause of the pandemic on
      regional and global basis. The largest proportion of HIV-1 infections in the year
      2000 was due to subtype C strains (47.2%). Subtype A/+CRF02_AG was estimated to
      be the second leading cause of the pandemic (27%), followed by subtype B strains
      (12.3%). The same analysis confirmed an increasing role of HIV-1 CRFs in the
      pandemic. The authors conclude that combined analysis of data based on the global
      HIV/AIDS surveillance and molecular virology studies provides for a useful model
      to monitor the dynamics of the global spread of HIV-1 subtypes and CRFs on
      regional and country levels-the information of potential importance for diagnosis
      and treatment of HIV/AIDS, as well as for the development globally effective HIV
      vaccines.

PMID- 11832691
TI  - High prevalence of HIV-1 and hepatitis C virus coinfection among injection drug
      users in the southeastern region of Yunnan, China.
AB  - The southeastern region of Yunnan province is a key site for drug trafficking and
      HIV-1 infection spread from the west of Yunnan and Laos to southeastern China. To
      investigate the prevalence of HIV-1 infection and hepatitis C virus (HCV)
      coinfection among injection drug users (IDUs) in southeastern Yunnan, three
      cohorts of 285 addicts, including 242 IDUs and 43 oral drug users, living in the
      cities of Gejiu and Kaiyuan and the county of Yanshan were studied. HIV-1 and HCV
      infections were detected by enzyme-linked immunosorbent assay and/or polymerase
      chain reaction. Data on the age, sex, risk behavior, drug use history,
      employment, ethnic background, and marriage status were obtained by interview.
      The overall prevalence of HIV-1 infection was 71.9%. The rate of HCV coinfection
      among 138 HIV-1-infected IDUs was 99.3%. Most HIV-infected IDUs were 20 to 35
      years old (86.7%) and were ethnic Han (75.9%), suggesting that the epidemic in
      Yunnan is no longer confined to non-Han ethnic minorities. HIV prevalence in
      female IDUs (81.2%) was significantly higher than in male IDUs (68.2%) ( p <.05).
      The prevalence of HIV infection reached 68.4% after 1 year of injection drug use.
      Needle/syringe sharing is the major high risk factor for the spread of HIV-1 and
      HCV infections. Large-scale educational campaigns are urgently needed to reduce
      the spread of HIV and HCV infection in these regions.

PMID- 11832692
TI  - Gender and clinical outcomes after starting highly active antiretroviral
      treatment: a cohort study.
AB  - OBJECTIVE: To examine gender differences in clinical response to highly active
      antiretroviral treatment (HAART). METHODS: A cohort of HIV-positive individuals
      was examined. Outcomes assessed were hospital admission and disease progression
      (either a new AIDS diagnosis or death) after starting HAART. Hazard ratios (HRs)
      derived using Cox regression methods compared female-to-male rates, adjusting for
      other factors independently associated with outcome. RESULTS: Four hundred ninety
      seven men and 146 women were followed up over a median of 13 months after
      starting HAART. Eighty-one percent of men were white, and 75% were homosexual.
      Fifty-eight percent of women were black African, and 86% were in the heterosexual
      risk category. The baseline CD4 count was higher in men than in women (191 vs.
      145 x 10; p < .01), but viral loads were similar (5.2 vs. 5.1 log copies/ml,
      respectively; p = .13). Fifty-six percent of men and women were treatment naive.
      Eighteen percent of men and women were admitted during follow-up, with 17% of
      male admissions and 12% of female admissions being the result of an AIDS-defining
      illness. The HR for admission was 0.76 (95% confidence interval [CI]: 0.46-1.27;
      p = .30) for women relative to men. Eleven percent of the men and 8% of the women
      experienced progression. Eighty-eight percent of progressions were the result of
      a new AIDS diagnosis (46 in men, 11 in women), and 8 men died. The HR for
      progression was 0.70 (CI: 0.36-1.33; p = .28). CONCLUSIONS: Our results suggest a
      possible benefit in women compared with men in the rate of outcomes after HAART.
      Further analysis with longer follow-up or greater numbers would enable a more
      powerful analysis to be performed.

PMID- 11832693
TI  - Vitamin A deficiency and genital tract infections in women living in Central
      Africa.

PMID- 11832694
TI  - Hepatitis C virus infection in long-term nonprogressor HIV-1-infected subjects.

PMID- 11832696
TI  - Addressing the challenges of adherence.
AB  - Adherence to antiretroviral therapy is a crucial determinant of treatment
      success. Studies have unequivocally demonstrated the close association between
      adherence and plasma HIV RNA levels, CD4 cell counts, and mortality in patients
      with HIV infection and disease. Adherence levels of > or =95% are required to
      maintain virologic suppression. However, actual adherence rates are often far
      lower; most studies show that 40% to 60% of patients are <90% adherent. Adherence
      also tends to decrease over time. Patients offer a range of reasons for
      nonadherence, but the most frequently cited one is simply that they forget; other
      reasons include being away from home, being busy, or experiencing a change in
      daily routine. Additional barriers to adherence include psychiatric disorders,
      such as depression or substance use, uncertainty about the effectiveness of
      treatment and the consequences of poor adherence, regimen complexity, and
      treatment side effects. Several strategies can be employed in the effort to
      support patients' adherence, and all members of the multidisciplinary team should
      ideally employ these strategies in combination. Efforts should be made to educate
      and motivate patients, simplify treatment regimens and tailor them to individual
      lifestyles, prepare for and manage side effects, and address the concrete issues
      that may be a barrier to adherence. Recruiting an adherence monitor, providing
      memory aids to medication taking, and anticipating course corrections can also
      help patients achieve the adherence rates needed for successful treatment of HIV
      infection and disease.

PMID- 11832697
TI  - Pharmacokinetic enhancement of protease inhibitors.
AB  - Protease inhibitor (PI)-enhanced regimens are becoming a standard of care in
      therapy for HIV infection. Many important questions remain regarding the optimal
      use of this treatment strategy. Multiple physiologic and pathologic factors
      influence the pharmacokinetic and pharmacodynamic profiles of PIs. Specifically,
      alterations in drug metabolism associated with inhibition or stimulation of the
      3A4 isozyme of the cytochrome P-450 enzyme system, activity of the P-glycoprotein
      intracellular transport system, and degree of plasma protein binding are all
      recognized as having important roles in influencing overall plasma PI
      concentrations and, ultimately, efficacy. Available pharmacokinetic data should
      include interpatient variation in plasma PI concentrations in addition to mean or
      median results. Viral inhibitory concentrations that have been corrected for the
      effect of protein binding should also be standardized. Studies to establish the
      concentration-response relationship for PIs may also prove beneficial in
      determining optimal plasma PI concentrations. Currently, therapeutic drug
      monitoring is not routinely recommended because of a lack of convincing clinical
      data as well as of a standard approach to collection and interpretation of drug
      concentrations. Large prospective studies are needed to further advance the
      usefulness of therapeutic drug monitoring.

PMID- 11832698
TI  - Role of sequencing in therapy selection.
AB  - The goals of sequencing antiretroviral agents are to preserve as many treatment
      options as possible, minimize drug toxicity, and prolong suppression of HIV.
      There are numerous options for sequencing antiretroviral agents when treatment
      fails. The most common reasons for treatment failure are the emergence of
      resistance and poor adherence. Data indicate that protease inhibitor therapy
      enhanced by ritonavir may delay the development of resistance longer than
      nonboosted protease inhibitor therapy. The results of using efavirenz or abacavir
      to simplify protease inhibitor treatment regimens for HIV-suppressed patients are
      promising. Although resistance to nonnucleoside reverse transcriptase inhibitors
      is a serious problem, sequencing them after zidovudine or abacavir therapy may be
      effective because of the hypersusceptibility to nonnucleoside reverse
      transcriptase inhibitors exhibited by viral populations in many nucleoside
      reverse transcriptase inhibitor-experienced patients. New antiretrovirals with
      greater tolerability, higher genetic barriers, and less cross-resistance than
      existing agents are needed to achieve further dramatic advances in treating HIV
      infection.

PMID- 11832699
TI  - Long-term exposure to lifelong therapies.
AB  - Three categories of highly active antiretroviral therapy (HAART)-associated major
      toxic effects have been identified: nucleoside-related toxic effects (e.g.,
      neuropathy, myopathy, pancreatitis, hepatic steatosis, lactic acidosis, and
      possibly lipoatrophy), metabolic complications (e.g., fat redistribution, insulin
      resistance, and hyperlipidemia), and bone disease (e.g., osteopenia and/or
      osteoporosis). The toxic effects caused by nucleosides are hypothesized to be a
      result of mitochondrial injury and include myopathy, pancreatitis, liver failure,
      and lactic acidosis. Alterations in lactic acid metabolism range from common
      instances of asymptomatic lactic acidemia to rare occurrences of life-threatening
      lactic acidosis with hepatic steatosis. A metabolic syndrome consisting of
      lipodystrophy (i.e., fat redistribution), hyperlipidemia and insulin resistance
      has been observed, particularly with protease inhibitor treatment. Some additive
      interaction between protease inhibitors and nucleosides has also been described.
      The potential relationship of these metabolic abnormalities to increased risk of
      cardiovascular disease and diabetes has broad implications on long-term patient
      management. Lipodystrophy associated with HAART is generally accompanied by
      potentially serious abnormalities, including dyslipidemia (i.e.,
      hypercholesterolemia and hypertriglyceridemia) and altered glucose metabolism
      (i.e., insulin resistance). Regimens of HAART may have adverse effects on bone
      metabolism, as indicated by emerging reports of osteopenia, osteoporosis, and
      avascular necrosis.

PMID- 11832700
TI  - Mycoplasma genitalium: another important pathogen of nongonococcal urethritis.
AB  - PURPOSE: We reviewed findings on the pathogenic role of Mycoplasma genitalium in
      nongonococcal urethritis and the treatment of men with M. genitalium positive
      nongonococcal urethritis. MATERIALS AND METHODS: We reviewed literature selected
      from peer reviewed journals listed in MEDLINE and from resources cited in those
      articles from 1967 to January 2001. RESULTS: M. genitalium was first isolated
      from 2 men with nongonococcal urethritis and thereafter it was shown to cause
      urethritis in subhuman primates inoculated intraurethrally. This mycoplasma has
      been detected significantly more often in patients with acute nongonococcal
      urethritis, particularly in those with nonchlamydial nongonococcal urethritis,
      than in those without urethritis. The prevalence of M. genitalium positive
      nonchlamydial nongonococcal urethritis is 18.4% to 45.5% of all nonchlamydial
      nongonococcal urethritis cases. In addition, the persistence of M. genitalium in
      the urethra after antimicrobial chemotherapy is associated with persistent or
      recurrent nongonococcal urethritis. M. genitalium is highly susceptible to
      tetracycline, macrolide and some new fluoroquinolones. The regimen of 100 mg.
      doxycycline orally twice daily for 7 days, which is recommended for chlamydial
      nongonococcal urethritis, seems to be effective for M. genitalium positive
      nongonococcal urethritis, although clinical data to substantiate this regimen are
      limited. CONCLUSIONS: The various results reported to date tend to support the
      proposition that M. genitalium is a pathogen of nongonococcal urethritis.
      However, currently diagnostic methods for this important mycoplasma are not
      available in clinical practice. Because of the possible association of the
      posttreatment presence of M. genitalium in the urethra with persistent or
      recurrent nongonococcal urethritis, eradication of this mycoplasma from the
      urethra is essential for managing M. genitalium positive disease. However,
      clinical data on treating M. genitalium positive nongonococcal urethritis are
      extremely limited. Thus, further studies are required to develop new diagnostic
      methods that would be available in clinical settings and establish a new
      treatment algorithm for nongonococcal urethritis, including M. genitalium
      positive disease.

PMID- 11832701
TI  - The use of fibrin sealant in urology.
AB  - PURPOSE: Fibrin sealant has been increasingly applied in various surgical fields,
      including urological surgery, in the last 2 decades. We determined the safety and
      efficacy of fibrin sealant in urological surgery and identified areas that need
      further clinical investigation. MATERIALS AND METHODS: A MEDLINE search of all
      available literature regarding the use of fibrin sealant was performed. All
      articles, including experimental animal studies, prospective and retrospective
      studies, case series and case reports of fibrin sealant for hemostasis and/or
      other urological applications, were identified and reviewed. RESULTS: Prospective
      randomized studies in the field of thoracic and trauma surgery show the efficacy
      and safety of fibrin sealant for hemostasis. Based on these data fibrin sealant
      has been used successfully for hemostasis during partial nephrectomy and
      traumatic renal reconstruction. A number of experimental animal studies, case
      series and case reports show the efficacy of fibrin sealant for ureteral
      anastomosis, microsurgical vasal anastomosis, fistula repair, circumcision and
      orchiopexy as well as it use as an adjunct in other areas of reconstruction.
      CONCLUSIONS: Fibrin sealant is an effective and safe topical agent for
      controlling surface bleeding during elective and trauma related urological
      procedures. Using fibrin sealant as an adhesive for reconstruction requires
      further prospective studies. The introduction of laparoscopic procedures in
      urology may expand the indications for fibrin sealant as an alternative method of
      tissue reapproximation. Limiting the routine use of fibrin sealant to procedures
      with demonstrable benefits is desirable and would lead to a cost saving approach.

PMID- 11832702
TI  - Purification of a human prostate specific antigen. 1979 [classical article].

PMID- 11832703
TI  - Expectant management of nonpalpable prostate cancer with curative intent:
      preliminary results.
AB  - PURPOSE: We evaluate a strategy of expectant management for men with stage T1c
      prostate cancer. MATERIALS AND METHODS: A total of 81 men (median age 65 years,
      range 52 to 72) with stage T1c prostate cancer who were thought to have small
      volume prostate cancer based on needle biopsy findings and prostate specific
      antigen (PSA) density were followed for more than 1 year with semiannual PSA and
      digital rectal examination, and annual prostate biopsies (median followup 23
      months, range 12 to 58). A recommendation for treatment was made if disease
      progression was indicated by unfavorable followup needle biopsy findings (Gleason
      pattern 4 or 5, greater than 2 biopsy cores with cancer, greater than 50%
      involvement of any core with cancer). Curable disease was defined on pathological
      examination of radical prostatectomy specimens as 1) organ confined cancer of
      Gleason score 7 or less, 2) cancer with extraprostatic extension of Gleason score
      7 (3+4) or less with negative margins, seminal vesicles and lymph nodes, or 3)
      cancer of Gleason score 6 or less regardless of margin status or extraprostatic
      extension if negative seminal vesicles and lymph nodes. RESULTS: Of the 81 men 25
      (31%) had progression of disease at followup. PSA density was statistically
      significantly higher (p = 0.01) and the percentage of free PSA was statistically
      significantly lower (p = 0.04) in men with compared to those without disease
      progression. Disease progression occurred in 22 of 39 men (56%) with every
      followup biopsy showing cancer compared to 3 of 42 (2%) men with 1 or more
      negative followup biopsies (p <0.001). Of the 25 men with progression 13
      underwent radical prostatectomy and 12 of 13 (92%) had curable cancers.
      CONCLUSIONS: Expectant management with curative intent may be a reasonable
      alternative for carefully selected older men who are thought to have small volume
      cancers.

PMID- 11832704
TI  - Comparison of helical computerized tomography and plain radiography for
      estimating urinary stone size.
AB  - PURPOSE: We evaluated the accuracy of noncontrast spiral computerized tomography
      (CT) for determining urinary stone size compared with plain x-ray. MATERIALS AND
      METHODS: We retrospectively analyzed noncontrast helical CT and plain x-ray of
      the kidneys, ureters and bladder images of 39 patients with urolithiasis who
      underwent each study from July 1997 to February 1999. Stone size on x-ray was
      measured in the craniocaudal and transverse dimensions by a single radiologist
      (I.C.B.). The size of the same stone was then determined on blinded noncontrast
      spiral CT images. Stones that were less than 3 mm. were excluded from study. On
      CT estimated craniocaudal dimension was based on collimation thickness, the
      reconstruction interval and the number of images on which the stone was
      visualized. RESULTS: We evaluated 58 stones 3 mm. or larger in the greatest
      dimension on plain x-ray of the kidneys, ureters and bladder, and noncontrast
      spiral CT, including 15 in the distal ureter, 7 in the mid or proximal ureter and
      36 in the kidneys. Stone size was 3 to 18 mm. in the greatest dimension. Mean
      transverse dimension of the stone plus or minus standard deviation on noncontrast
      spiral CT was 5.1 +/- 1.08 versus 4.9 +/- 1.08 mm. on plain x-ray of the kidneys,
      ureters and bladder (paired t test; p = 0.335). The mean craniocaudal dimension
      on noncontrast spiral CT was 7.5 +/- 1.98 versus 6.7 +/- 1.98 mm. on plain x-ray
      paired t test (p = 0.005). CONCLUSIONS: Noncontrast spiral CT enables a similar
      measurement of stone size along the transverse dimension as plain x-ray of the
      kidneys, ureters and bladder. In individuals noncontrast spiral CT does not
      accurately measure the craniocaudal dimension of stones compared with plain x-ray
      when standard acquisition and reconstruction techniques are used. In this regard
      it has a tendency to overestimate stone size by an average of 0.8 mm.

PMID- 11832705
TI  - Risk factors for the formation of a steinstrasse after extracorporeal shock wave
      lithotripsy: a statistical model.
AB  - PURPOSE: We studied the various stone, renal and therapy factors that could
      affect steinstrasse formation after extracorporeal shock wave lithotripsy (ESWL),
      Dornier Medical Systems Inc., Marietta, Georgia to define the predictive factors
      for its formation. Thus, steinstrasse could be anticipated and prophylactically
      avoided. MATERIALS AND METHODS: Between February 1989 and May 1999, 4,634
      patients were treated with a Dornier MFL 5000 lithotriptor (Dornier Med Tech,
      GmbH, Germany). Renal stones were encountered in 3,403 patients and ureteral
      stones in 1,231. Steinstrasse were recorded in 184 patients, of whom 74 required
      intervention and formed the "complicated group." All patient data, stone and
      renal characteristics, and data of ESWL were reviewed. Univariate and
      multivariate statistical analyses of patients, stones and therapy characteristics
      in correlation with the incidence of steinstrasse formation were performed to
      assign the factors that had a significant impact on steinstrasse formation.
      RESULTS: The overall incidence of steinstrasse was 3.97%. The steinstrasse was in
      the pelvic ureter in 74% of the cases, lumbar ureter in 21.7% and iliac ureter in
      4.3%. Steinstrasse incidence significantly correlated with stone size and site,
      the power level (kV.) used during therapy and radiological renal features.
      Steinstrasse was more common with renal stones more than 2 cm. in diameter in a
      dilated system, especially with the use of high power (greater than 22 kV.) for
      disintegration. A statistical model was constructed to estimate the risk of
      steinstrasse formation accurately. CONCLUSIONS: Stone size and site, renal
      morphology and shock wave energy are the significant predictive factors
      controlling steinstrasse formation. If a patient has a high probability of
      steinstrasse formation, close followup with early intervention or prophylactic
      pre-ESWL ureteral stenting is indicated.

PMID- 11832706
TI  - The effect of bench model fidelity on endourological skills: a randomized
      controlled study.
AB  - PURPOSE: Complex skills, such as ureteroscopy and stone extraction, are
      increasingly taught to novice urology trainees using bench models in surgical
      skills laboratories. We determined whether hands-on training improved the
      performance of novices more than those taught only by a didactic session and
      whether there was a difference in the performance of subjects taught on a low
      versus a high fidelity model. MATERIALS AND METHODS: We randomized 40 final year
      medical students to a didactic session or 1 of 2 hands-on training groups
      involving low or high fidelity bench model practice. Training sessions were
      supervised by experienced endourologists. Testing involved removal of a mid
      ureteral stone using a semirigid ureteroscope and a basket. Blinded examiners
      tested subjects before and after training. Performance was measured by a global
      rating scale, checklist, pass rating and time needed to complete the task.
      RESULTS: There was a significant effect of hands-on training on endourological
      performance (p <0.01). With respect to bench model fidelity the low fidelity
      group did significantly better than the didactic group (p <0.05). However, no
      significant difference was found between the high and low fidelity groups (p
      >0.05). The low fidelity model cost Canadian $20 to produce, while the high
      fidelity model cost Canadian $3,700 to purchase. CONCLUSIONS: Hands-on training
      using bench models can be successful for teaching novices complex endourological
      skills. A low fidelity bench model is a more cost-effective means of teaching
      ureteroscopic skills to novices than a high fidelity model.

PMID- 11832707
TI  - Laparoscopic management of caliceal diverticular calculi.
AB  - PURPOSE: We describe laparoscopic techniques for the definitive management of
      symptomatic caliceal diverticular stone disease. MATERIALS AND METHODS: Five
      patients underwent retroperitoneoscopic management of a symptomatic, stone
      bearing caliceal diverticulum. Techniques for intraoperative localization of the
      stone bearing diverticulum included retrograde injection of indigo carmine,
      fluoroscopy and/or laparoscopic ultrasound. In 2 cases the patent neck of the
      diverticulum was sutured via laparoscopy. RESULTS: Complete stone clearance and
      obliteration of the diverticular cavity was achieved in all cases without any
      open conversion. Mean operative time was 133.8 minutes. Mean estimated blood loss
      was less than 50 cc in 4 cases and 150 cc in 1. Mean hospital stay was 36 hours.
      There were no laparoscopic or postoperative complications. CONCLUSIONS: The
      laparoscopic approach to symptomatic caliceal diverticula represents an effective
      and minimally invasive modality for complete clearance of the stone burden and
      definitive management of the anatomical abnormality. However, patient selection
      is paramount. We reserve the laparoscopic approach for symptomatic caliceal
      diverticula with thin overlying renal parenchyma, or for anterior lesions
      inaccessible to or unsuccessfully managed by endourological techniques. A
      decision tree algorithm for managing symptomatic caliceal diverticular calculi is
      proposed.

PMID- 11832708
TI  - Laparoscopic pyeloplasty: the first 100 cases.
AB  - PURPOSE: Laparoscopic pyeloplasty was developed as a minimally invasive
      alternative to an open procedure for the treatment of ureteropelvic junction
      obstruction. Long-term followup has not yet been reported. We present experience
      with the first 100 consecutive cases of laparoscopic pyeloplasty performed at our
      institution. MATERIALS AND METHODS: A retrospective review of 100 consecutive
      laparoscopic pyeloplasties in 99 patients (means age 37.3 years) between August
      1993 and January 1999 was performed. All patients had radiographic evidence of
      obstruction with signs, symptoms or deterioration of renal function. Repair was
      for primary ureteropelvic junction obstruction in 83 patients and secondary
      obstruction in 17. The 4 types of repairs performed were Anderson-Hynes
      dismembered (71 cases), Y-V plasty (20), Heineke-Mirhulicz (8) and Davis
      intubated ureterotomy (1). Type of repair used was dictated by intraoperative
      findings. Twenty patients had nonobstructing renal stones and underwent
      concomitant pyelolithotomy. All patients were assessed for symptoms and
      radiographic evaluation for anatomical obstruction. RESULTS: Average operating
      room time was 4.2 hours, which decreased with surgeon experience. Average blood
      loss was 181 cc and hospital stay was 3.3 days. Two patients required blood
      transfusion. A crossing vessel was found in 57 patients. With a mean clinical and
      radiographic followup of 2.7 and 2.2 years, respectively, 96% of the patients
      were free of obstruction on followup radiographic imaging. Of the patients who
      underwent concomitant pyelolithotomy, 18 (90%) were stone-free at last followup.
      All failures occurred within the first postoperative year. There were 12
      complications in this series. CONCLUSIONS: In experienced hands laparoscopic
      pyeloplasty is an effective alternative treatment for symptomatic ureteropelvic
      junction obstruction. The results appear durable and comparable to open
      pyeloplasty with decreased postoperative morbidity.

PMID- 11832709
TI  - Long-term followup after laparoscopic radical nephrectomy.
AB  - PURPOSE: Laparoscopic radical nephrectomy has been shown to be less morbid than
      traditional open radical nephrectomy. The long-term oncological effectiveness of
      laparoscopic radical nephrectomy remains to be established. MATERIALS AND
      METHODS: At 3 centers patients undergoing laparoscopic radical nephrectomy before
      November 1, 1996 with pathologically confirmed renal cell carcinoma were
      identified. A representative group of patients undergoing open radical
      nephrectomy for clinical T1, T2 lesions was also identified. Staging, operative
      details and postoperative course were reviewed. Followup consisted of review of
      clinical, laboratory and radiological records. Kaplan-Meier analysis was
      performed. RESULTS: The study included 64 patients treated with laparoscopic and
      69 treated with open radical nephrectomy with respective average ages of 60.6 and
      61.3 years at surgery. On preoperative imaging open lesions were larger (6.2 cm.,
      range 2.5 to 15) than laparoscopic radical nephrectomy lesions (4.3 cm., range 2
      to 10, p <0.001). Pathology reports revealed no difference in specimen weight
      (425 and 495 gm., p = 0.146) or average Fuhrman grade (1.88 and 1.78, p = 0.476)
      between laparoscopic and open radical nephrectomy, respectively. Median followup
      was 54 months (range 0 to 94) for laparoscopic and 69 months (range 8 to 114) for
      open radical nephrectomy. Kaplan-Meier analysis with log rank comparison revealed
      5-year recurrence-free survival of 92% and 91% for laparoscopic and open radical
      nephrectomy, respectively (p = 0.583). At 5 years cancer specific survival was
      98% and 92% (p = 0.124), and nonspecific survival was 81% and 89% (p = 0.260) for
      laparoscopic and open radical nephrectomy, respectively. CONCLUSIONS:
      Laparoscopic radical nephrectomy confers long-term oncological effectiveness
      equivalent to traditional open radical nephrectomy.

PMID- 11832710
TI  - Laparoscopic management of congenital seminal vesicle cysts associated with
      ipsilateral renal agenesis.
AB  - PURPOSE: Congenital cysts of the seminal vesicles associated with ipsilateral
      renal abnormalities are rare. When they are symptomatic, open surgical excision
      has been the treatment of choice. We present our experience with laparoscopic
      management and provide a detailed literature review of this entity. MATERIALS AND
      METHODS: Since 1985, 3 patients with symptomatic seminal vesicle cysts and
      ipsilateral renal agenesis have been treated at our center. Open surgical
      excision was performed in 1 patient and laparoscopic management was performed in
      the other 2. RESULTS: Mean patient age was 35.7 years (range 30 to 42).
      Presenting symptoms were perineal pain in all 3 cases, dysuria in 2, irritable
      voiding in 2 and testicular pain in 1. Mean laparoscopic operative time was 195
      minutes and mean estimated blood loss was 325 cc. Transabdominal or transrectal
      ultrasound was performed in 2 cases and computerized tomography was performed in
      all 3. CONCLUSIONS: Seminal vesicle cysts associated with ipsilateral renal
      agenesis are rare but they should be considered in men with otherwise
      inexplicable irritable voiding symptoms, perineal discomfort or other
      genitourinary complaint of unclear etiology. Evaluation should include digital
      rectal examination, transrectal and transabdominal ultrasound, computerized
      tomography and cystoscopy. Laparoscopy provides excellent intraoperative access
      and visualization with minimal postoperative morbidity. It is likely to become
      the treatment of choice for this rare developmental anomaly.

PMID- 11832711
TI  - Percutaneous renal cryoablation of renal tumors in patients with von Hippel
      Lindau disease.
AB  - PURPOSE: We determine the feasibility and safety of performing percutaneous
      cryoablation of renal tumors in patients with von Hippel-Lindau disease.
      MATERIALS AND METHODS: We selected 2 men and 2 women with von Hippel-Lindau
      disease and radiographic determined solid renal tumors were selected to undergo
      percutaneous cryoablation. All patients underwent standard preoperative
      evaluation. An interventional magnetic resonance imaging unit was used for probe
      guidance and ice ball monitoring. The cryoablation procedure was performed with a
      2 or 3 mm. cryoprobe using a pressurized argon gas system for ice ball formation.
      The patients were hospitalized overnight for observation and discharged home the
      following day. A followup computerized tomogram or magnetic resonance imaging
      scan was performed at 1 week, 1, 3, 6 and 12 months and every 6 months
      thereafter, along with physical examination, urinalysis, serum blood urea
      nitrogen and creatinine. RESULTS: A total of 5 tumors were treated ranging from
      2.8 to 5.0 cm. in diameter. All patients underwent the procedure without
      difficulty with 2 requiring re-treatment due to residual tumor for a total of 7
      treatments. At followup from 2 to 23 months there has been no radiographic
      evidence of recurrence at the cryoablated areas. CONCLUSIONS: Percutaneous
      cryoablation of renal tumors in patients with von Hippel-Lindau disease proved to
      be successful in this initial series. Although 2 patients had residual tumor
      after the initial cryoablation procedure re-treatment was performed with no
      adverse sequela. This minimally invasive therapy may allow patients with von
      Hippel-Lindau disease to avoid the necessity of multiple open surgical
      procedures.

PMID- 11832712
TI  - Assessment of tumor invasion of the vena caval wall in renal cell carcinoma cases
      by magnetic resonance imaging.
AB  - PURPOSE: We evaluated the role of magnetic resonance imaging (MRI) in patients
      with renal cancer and inferior vena caval involvement with reference to its
      ability to characterize the extent and nature of inferior vena caval tumor
      extension and wall invasion. MATERIALS AND METHODS: The study included 12
      consecutive patients with renal cancer and inferior vena caval involvement. All
      patients underwent imaging on a 1.5 Tesla MRI unit. Coronal, axial T1 and axial
      T2-weighted images were performed in all cases, while in 6 3-dimensional
      gadolinium enhanced magnetic resonance angiography and venography were also
      performed. Images were assessed for the extent and nature of tumor extension,
      that is tumor versus thrombus, and invasion of the inferior vena caval wall.
      Imaging results were compared with operative findings. RESULTS: On MRI the extent
      and nature of the inferior vena caval tumor was correctly defined in all cases.
      The sensitivity, specificity and accuracy of inferior vena caval wall invasion
      were 100%, 89% and 92%, respectively. CONCLUSIONS: In patients with renal cancer
      and inferior vena caval involvement MRI defines the tumor level in the inferior
      vena cava. It is also a sensitive technique for detecting vessel wall invasion
      and provides important preoperative information for surgical planning.

PMID- 11832713
TI  - Prospective evaluation of genetic abnormalities and telomerase expression in
      exfoliated urinary cells for bladder cancer detection.
AB  - PURPOSE: To evaluate alternative procedures to cytoscopic examination we
      prospectively compared noninvasive procedures for detecting bladder cancer namely
      cytology, loss of heterozygosity (LOH), microsatellite instability and human
      telomerase catalytic subunit reverse transcriptase (hTERT) messenger (m) RNA
      detection. MATERIALS AND METHODS: Specificity and cutoff values were established
      in the blood and urine sediment of 50 controls. Sensitivity was analyzed in the
      urine and tissue samples of 50 patients with bladder cancer. The diagnosis was
      established by cystoscopic and histological examination. Genomic alterations were
      studied using a panel of 24 microsatellite markers to detect LOH events, while 3
      additional mononucleotide repeats were analyzed for microsatellite instability
      detection. Telomerase expression was detected in urinary cells by nested RT
      polymerase chain reaction amplification of hTERT mRNA. All techniques were
      compared by cytological examination. RESULTS: Sensitivity and specificity were
      31% and 100% for cytological testing, 96% and 100% for LOH, and 75% and 69% for
      RT-polymerase chain reaction of hTERT, respectively. No alteration was detected
      on microsatellite instability analysis in urine or tumor tissue cells. Using only
      the 5 markers most strongly associated with bladder cancer selected by logistic
      regression analysis, namely ABL1, IFNa, D9S12, MJD58 and D18S364, LOH test
      sensitivity slightly decreased to 90%. CONCLUSIONS: Urinary LOH analysis was the
      most sensitive and specific method for bladder cancer detection and it appeared
      less dependent on urine sediment quality. The logistic regression score may be an
      interesting complement to cystoscopy. The specificity of hTERT mRNA detection was
      incomplete since false-positives were observed in 31% of cases. Absent
      microsatellite instability in our cohort showed that these genomic alterations
      are not present at the early step of bladder cancer.

PMID- 11832714
TI  - Over expression of CD44V8-10 in urinary exfoliated cells as an independent
      prognostic predictor in patients with urothelial cancer.
AB  - PURPOSE: CD44 is a widely expressed cell surface adhesion molecule, of which
      various isoforms arise from alternative RNA splicing mechanisms. Over expression
      of specific CD44 splice variants, namely CD44v8-10, is evident in various
      malignant tumors and is considered to be associated with disease progression. In
      this study, we investigated whether the transcriptional level of CD44v8-10
      relative to that of the standard CD44 isoform would predict the extent and
      prognosis of urothelial cancer. MATERIALS AND METHODS: The CD44v8-10- to 
      standard CD44 ratio was measured in the tissue (40 urothelial cancer specimens
      and corresponding normal urinary tissue) and spontaneously voided urine samples
      of 150 patients with urothelial cancer and 50 with benign urological disease by
      reverse transcriptase-polymerase chain reaction using the set of primers capable
      of amplifying all CD44 splice variant isoforms. RESULTS: Initially any CD44
      variant isoforms were barely detectable in normal urinary tissues, whereas CD44v8
      10 was predominantly expressed in most urothelial cancer specimens. Furthermore,
      the CD44v8-10- to -standard CD44 ratio in urothelial cancer was closely
      associated with tumor progression. We then compared the ratio in urothelial
      cancer tissue and urinary exfoliated cells, and noted a linear and significant
      correlation of these 2 values in the same patients. Therefore, we investigated
      whether the CD44v8-10- to -standard CD44 ratio in urinary exfoliated cells would
      predict the prognosis and disease progression. The mean ratio in the urinary
      exfoliated cells of patients with invasive urothelial cancer was significantly
      higher than in those with superficial urothelial cancer. Of the patients with
      superficial bladder cancer disease-free survival rate of those with an elevated
      versus a normal ratio was significantly lower. Moreover, of the patients with
      advanced urothelial carcinoma who underwent complete resection disease-free
      survival of those with an elevated CD44v8-10- to -standard CD44 ratio was
      significantly lower than that of patients with a normal ratio. CONCLUSIONS: These
      results indicate that CD44v8-10 is strongly expressed in tumor tissue and evident
      at high levels in urinary exfoliated cells of patients with invasive versus
      superficial urothelial cancer. An elevated CD44v8-10- to -standard CD44 ratio in
      urinary exfoliated cells may serve as a novel prognostic predictor and indicator
      of disease extent in patients with urothelial cancer.

PMID- 11832716
TI  - Impact of the number of lymph nodes retrieved on outcome in patients with muscle
      invasive bladder cancer.
AB  - PURPOSE: We postulate that the number of lymph nodes examined in cystectomy
      specimens can have an impact on the outcome of patients with bladder cancer.
      MATERIALS AND METHODS: We analyzed data on 322 patients with muscle invasive
      bladder cancer who underwent radical cystectomy and bilateral pelvic
      lymphadenectomy. We evaluated the associations of the number of lymph nodes
      identified by the pathologist in the surgical specimen with the local recurrence
      rate and survival outcome. RESULTS: Patients were divided into groups by lymph
      node status and the distribution of the number of lymph nodes examined. In stages
      pN0 and pN+ cases improved survival was associated with a greater number of lymph
      nodes examined. We determined that at least 9 lymph nodes should be studied to
      define lymph node status accurately. CONCLUSIONS: These results indicate that
      surgical resection and pathological assessment of an adequate number of lymph
      nodes in cystectomy specimens increases the likelihood of proper staging and
      impacts patient outcome. Such information is important not only for the therapy
      and prognosis of individuals, but also for identifying those who may benefit from
      adjuvant chemotherapy.

PMID- 11832717
TI  - Testicular tumors in Carney's complex.
AB  - PURPOSE: Bilateral sex cord stromal testicular tumors are common in the syndrome
      of myxoma, spotty pigmentation and endocrine overactivity (Carney's complex).
      Large cell calcifying Sertoli cell tumor is the particular testicular tumor found
      in Carney's complex. A clinicopathological review of 26 patients is presented.
      MATERIALS AND METHODS: We report 2 cases of Carney's complex with testicular
      tumors. An additional 24 patients with Carney's complex and testicular tumors
      were identified by MEDLINE search and review of the literature. RESULTS:
      Bilateral testicular tumors were found in 16 patients (61%) with a familial
      occurrence in 10 (38%). A testicular mass was the most common presentation. The
      associated findings of Carney's complex included cardiac myxoma in 16 patients,
      skin myxoma in 16, skin pigmentation in 15, Cushing's syndrome in 8, acromegaly
      in 3 and schwannoma in 3. Excisional biopsy, surveillance, bilateral orchiectomy
      and unilateral orchiectomy were performed in 7, 4, 7 and 8 patients,
      respectively. CONCLUSIONS: No local tumor recurrence or metastasis has developed
      in patients with bilateral and/or multifocal testicular tumors. Excisional biopsy
      or surveillance only are treatment options for bilateral testicular tumors in
      Carney's complex.

PMID- 11832715
TI  - Role of mitochondria in ciprofloxacin induced apoptosis in bladder cancer cells.
AB  - PURPOSE: In our earlier series we showed that ciprofloxacin inhibits bladder
      tumor cell growth with concomitant S/G2M cell cycle arrest and reported an
      increased Bax-to-Bcl-2 ratio in cells undergoing cell death. In the current
      series we elucidated the molecular mechanisms by which ciprofloxacin induces
      apoptotic processes. MATERIALS AND METHODS: Ciprofloxacin mediated mitochondrial
      depolarization was detected by flow cytometry in HTB9 cells. Mitochondrial
      permeability transition was measured by spectrophotometry in isolated
      mitochondria treated with ciprofloxacin in the presence and absence of
      cyclosporin. The consequential decrease in mitochondrial calcium, cytochrome c
      release and Bax translocation to mitochondria, which resulted in the activation
      of caspase 3 leading to apoptotic cell death, was measured by biochemical and
      confocal microscopy. RESULTS: Mitochondrial depolarization was observed during
      ciprofloxacin induced apoptotic processes. Cyclosporin A, a known inhibitor of
      the mitochondrial permeability transition pore, protected cells against decreased
      mitochondrial potential. Also, ciprofloxacin induced an alteration of
      mitochondrial calcium as early as 5 minutes and this disruption of intracellular
      calcium homeostasis was prevented by cyclosporin. Ciprofloxacin also had a direct
      effect on swelling of isolated mitochondria, which was absent in the presence of
      cyclosporin. Mitochondrial changes were accompanied by cytochrome c release and
      caspase 3 activation. Our findings also showed Bcl-2 dependent subcellular
      redistribution of Bax to the mitochondrial membrane in ciprofloxacin treated
      bladder tumor cells. CONCLUSIONS: The disruption of calcium homeostasis,
      mitochondrial swelling and redistribution of Bax to the mitochondrial membrane
      are key events in the initiation of apoptotic processes in ciprofloxacin treated
      bladder cancer cells.

PMID- 11832718
TI  - Prostate cancer screening with prostate specific antigen in spinal cord injured
      men.
AB  - PURPOSE: As the spinal cord injured population ages, prostate cancer becomes a
      more significant cause of potential mortality. Consequently due to various
      bladder management techniques the validity of standard prostate specific antigen
      (PSA) screening values in this population must be evaluated. We compared
      screening PSA values in a large population of spinal cord injured patients with
      those in age matched, nonspinal cord injured men. MATERIALS AND METHODS:
      Screening PSA values were obtained using the AxSYM assay (Abbott Laboratories,
      Abbott Park, Illinois) in 366 spinal cord injured men 40 to 79 years old. In
      those with PSA elevated to greater than 4 ng./ml. who consented to further
      evaluation standard sextant needle biopsy of the prostate were performed under
      transrectal ultrasound guidance. Data were compared with data on 371 randomly
      selected, age matched controls from the Baylor College of Medicine community
      screening program database of more than 19,000 patient-tests. Analysis was
      performed with the unpaired Student t test. RESULTS: When we divided patients 40
      to 80 years old into 4 age groups by decade and compared them with normal
      controls by decade, there was no statistically significant difference in mean PSA
      in the 2 groups. Of 18 spinal cord injured patients with PSA greater than 4
      ng./ml. 12 underwent transrectal ultrasound guided needle biopsy of the prostate
      and 6 refused further evaluation. Five of these biopsies (1.3% overall) were
      positive and 7 were negative for adenocarcinoma. CONCLUSIONS: As in healthy men,
      PSA and digital rectal examination can be performed in spinal cord injured men to
      screen for prostate cancer. None of the various bladder management techniques in
      these cases seemed to affect screening results.

PMID- 11832719
TI  - Percent free prostate specific antigen is not an independent predictor of organ
      confinement or prostate specific antigen recurrence in unscreened patients with
      localized prostate cancer treated with radical prostatectomy.
AB  - PURPOSE: We studied the controversial relationship of percent free prostate
      specific antigen (PSA) with organ confined prostate cancer and PSA failure after
      radical prostatectomy. MATERIALS AND METHODS: We tested the characteristics of
      the percent free PSA monoclonal Immulite DPC Immunoassay (Diagnostic Products
      Corp., Los Angeles, California) for predicting organ confinement in 698
      consecutive unscreened men treated only with radical prostatectomy between 1995
      and 2000. In addition, we assessed the ability of percent free PSA to predict
      post-radical prostatectomy PSA failure, defined as PSA 0.1 ng./ml. or greater, in
      a subset of 581 men in whom followup was available. All statistical analyses were
      repeated for stage T1c cancer with PSA between 2 and 10 ng./ml. RESULTS: On
      univariate analyses percent free PSA achieved significance for predicting organ
      confined disease at all clinical stages (p <0.001) and for stage T1c cancer with
      PSA between 2 and 10 ng./ml. (p = 0.012). However, significance dissipated after
      controlling for total PSA, biopsy Gleason sum and clinical stage (p = 0.135 and
      0.851, respectively). In univariate Cox models percent free PSA failed to predict
      PSA failure across stages (p = 0.341), as well as in stage T1c cancer (p = 0.93).
      In multivariate analyses controlling for traditional PSA biopsy grade and
      clinical stage (p <0.001), percent free PSA failed to contribute to predicting
      PSA failure (p = 0.342). In the stage T1c subset biopsy Gleason sum (p <0.001)
      and PSA (p = 0.018) remained significant, in contrast to percent free PSA (p =
      0.237). CONCLUSIONS: Percent free PSA has no independent, statistically
      significant association with organ confined status or posttreatment PSA outcome
      in unscreened patients who undergo radical prostatectomy for localized prostate
      cancer.

PMID- 11832720
TI  - A standard definition of disease freedom is needed for prostate cancer:
      undetectable prostate specific antigen compared with the American Society of
      Therapeutic Radiology and Oncology consensus definition.
AB  - PURPOSE: Freedom from prostate cancer is defined by undetectable prostate
      specific antigen (PSA) after surgery and the American Society of Therapeutic
      Radiology and Oncology (ASTRO) criteria are recommended for irradiation. Whether
      these definitions of disease freedom are comparable was evaluated in this study.
      MATERIALS AND METHODS: From August 1992 to August 1996 simultaneous irradiation
      with prostate 125iodine implantation followed by external beam irradiation was
      performed in 591 consecutive men with stage T1T2NX prostate cancer. All patients
      had a transperineal implant and none received neoadjuvant hormones. Disease
      freedom was defined by a PSA cutoff of 0.2 ng./ml. and the ASTRO consensus
      definition. Median followup was 6 years (range 5 to 8). RESULTS: Of the 591 men
      in this study 65 had recurrence by ASTRO criteria and 93 had recurrence by a PSA
      cutoff of 0.2 ng./ml., which was a significant difference (p = 0.001). On
      multivariate analysis of the factors related to disease-free status the
      definition of disease freedom, pretreatment PSA and Gleason score were highly
      significant. Of the 528 men with a minimum 5-year PSA followup the 8-year disease
      free survival rate by ASTRO criteria was 99% in those who achieved a PSA nadir of
      0.2 ng./ml. and 16% in those with a nadir of 0.3 to 1 ng./ml. Of the 469 disease
      free patients by ASTRO criteria with a minimum 5-year followup 455 (97%) achieved
      a PSA nadir of 0.2 ng./ml. or less. CONCLUSIONS: The definition of freedom from
      prostate cancer significantly affects treatment results. A standard definition is
      needed and a PSA cutoff of 0.2 ng./ml. is suggested as the standard for all
      curative treatments for localized prostate cancer.

PMID- 11832721
TI  - Multi-institutional experience with buccal mucosa onlay urethroplasty for bulbar
      urethral reconstruction.
AB  - PURPOSE: Buccal mucosa has been advocated as an ideal graft material for urethral
      reconstruction. We report our multicenter experience with buccal mucosa ventral
      onlay urethroplasty for complex bulbar urethral reconstruction in adults.
      MATERIALS AND METHODS: A retrospective analysis of patients who had undergone
      buccal onlay urethroplasty at 4 military medical treatment facilities
      participating in the Uniformed Services Urology Research Group was performed. The
      database generated included demographic data, genitourinary history, preoperative
      symptoms (American Urological Association symptom score), preoperative urinary
      flow rate, stricture length and operative statistics. Postoperative followup data
      included symptom score, flow rate, retrograde urethrogram results, and
      complications. RESULTS: A total of 53 patients (average age 32 years, range 17 to
      64) underwent buccal mucosa graft urethroplasty between January, 1996 and March,
      1998 for refractory strictures. Sixteen patients had undergone an average of 2.2
      prior endoscopic procedures (range 1 to 7). Average stricture length was 3.6 plus
      or minus standard deviation 1.8 cm. (range 2 to 7.5) as measured on preoperative
      retrograde urethrogram. Followup averaged 25 months (range 11 to 40 months).
      Average symptom scores decreased from 21.2 (range 14 to 33) preoperatively to 5.4
      (range 3 to 8) postoperatively (p <0.001). Average peak urinary flow rates
      increased from 7.9 preoperatively to 30.1 ml. per second postoperatively (p
      <0.001). Postoperative retrograde urethrograms were available for 34 patients and
      were normal in 24. The overall complication rate was 5.4%. Three patients
      required endoscopic incisions. One patient has a recurrent narrowing and
      treatment is considered a failure. There were 4 sacculations (7.5%) and 6
      narrowings, 3 of which required further treatment. Of the patients 50 required no
      additional procedures (94.3%). CONCLUSIONS: Buccal mucosa grafts used as a
      ventral onlay for bulbar urethral reconstruction yield reproducibly excellent
      results with minimal morbidity and low complication rates. Longer followup will
      be required to confirm the durability of our results.

PMID- 11832722
TI  - The BTA stat test is nonspecific for hematuria: an experimental hematuria model.
AB  - PURPOSE: An experimental hematuria model was designed to determine whether the
      bladder tumor antigen (BTA) stat test (Bion Diagnostics, Redmond, Washington) is
      influenced by microscopic or macroscopic hematuria. MATERIALS AND METHODS: A
      total of 25 healthy subjects provided urine and blood samples for the study. All
      subjects had a negative BTA stat test initially. Normal urine was mixed with
      autologous blood to cause hematuria of 3 degrees of severity. The test was
      performed in each sample after the creation of hematuria. RESULTS: BTA stat assay
      specificity in the presence of microscopic and gross hematuria was 80% and 24%,
      respectively. Results varied depending on the severity of hematuria, that is 20%
      for microscopic and 76% for gross hematuria. CONCLUSIONS: The results of the BTA
      stat test in the presence of microscopic hematuria must be interpreted in regard
      to the degree of hematuria. The test is not reliable in urine samples with gross
      hematuria due to a high false-positive rate.

PMID- 11832723
TI  - Routine postoperative intensive care monitoring is not necessary after radical
      cystectomy.
AB  - PURPOSE: Patients undergoing radical cystectomy have historically required
      intensive care monitoring in the perioperative period. We examined the
      postoperative care of these patients since the institution of a clinical care
      pathway with special attention to the need for intensive care unit admission.
      MATERIALS AND METHODS: We reviewed the records of 304 consecutive patients who
      underwent radical cystectomy from December 1995 to July 2000. Variables examined
      were the location and nature of postoperative care, American Society of
      Anesthesiologists score, estimated blood loss, transfusion requirement, hospital
      stay, perioperative minor complications, major complications, the mortality rate
      and urinary diversion type. RESULTS: Of the 304 patients 20 (6.5%) required
      intensive care unit monitoring during postoperative recovery and 18 were admitted
      directly to the intensive care unit postoperatively. Compared with the total
      population those admitted to the intensive care unit had increased hospital stay
      (p = 0.002), higher American Society of Anesthesiologists score (p <0.001),
      higher transfusion requirement (p = 0.001) and shorter operative time (p = 0.02).
      Patients who received blood transfusion and those with major complications were
      more likely to need intensive care unit care (p = 0.019 and <0.001,
      respectively). A single patient died who did not receive intensive care unit
      care. CONCLUSIONS: Our clinical care pathway outlines postoperative care on the
      regular urology floor for patients who undergo radical cystectomy. This policy
      has been safe and efficacious. We believe that admission to the intensive care
      unit should only be done in select cases.

PMID- 11832724
TI  - A multicenter study of the morbidity of radical cystectomy in select elderly
      patients with bladder cancer.
AB  - PURPOSE: We evaluated the morbidity of radical cystectomy for invasive bladder
      cancer in select patients older than 75 years using recent data from 2 academic
      hospitals. MATERIALS AND METHODS: We analyzed 73 radical cystectomies performed
      from January 1995 to June 2000 in patients 75 to 89 years old (median age 79.3).
      Cases were categorized according to the American Society of Anesthesiologists
      classification with a score of 2 in 41, 3 in 30 and 4 in 2. External urinary
      diversion was performed in 51 cases and an ileal neobladder was constructed in
      22. We evaluated the incidence and type of complications, clinical outcome, and
      postoperative care unit and hospital stay. Statistical analysis was done using
      the chi-square and Student t tests. RESULTS: Median operative time was 263
      minutes (range 95 to 451). The perioperative mortality rate was 2.7%. The
      intraoperative, early and late postoperative complication rates were 38.4%, 46.5%
      and 16.4%, respectively. Three reoperations (4.1%) were necessary. The most
      common early complications were pyelonephritis in 12.3% of cases, disorientation
      in 10.9%, pneumonia in 8.2% and prolonged ileus in 12.3%. The most common late
      complications were ureteroileal anastomotic stenosis in 5 cases and hernia in 3.
      Median postoperative care unit and hospital stays were 12 and 34 days,
      respectively. At a median followup of 14.4 months (range 6 to 74) the overall
      mortality rate was 31.5%. Hospital stay was significantly higher in patients with
      complications. The incidence of complications was similar in the 2 groups.
      CONCLUSIONS: These data support the aggressive surgical management of bladder
      cancer in select elderly patients. A rigorous multidisciplinary team approach can
      provide acceptable perioperative morbidity.

PMID- 11832725
TI  - Management of the postpubertal patient with cryptorchidism: an updated analysis.
AB  - PURPOSE: Management of the postpubertal cryptorchid testis depends on patient age
      at presentation. Based on the belief that the risk of death from surgery first
      exceeds the risk of death from testis cancer at age 32 years patients younger
      than 32 years are advised to undergo orchiectomy, while those older than 32 years
      are advised to remain under close observation. However, the data on which this
      recommendation is based are now a quarter-century old. During this interval
      significant improvements have been made in perioperative care and germ cell tumor
      therapy. We revisited the topic using contemporary data to determine whether and
      how recommendations on management of the postpubertal cryptorchid testis should
      be changed. MATERIALS AND METHODS: Contemporary data on germ cell mortality in
      the United States were obtained from the National Center for Health Statistics.
      From these data the lifetime risk of death from germ cell cancer in the general
      population was calculated for each 5-year interval between ages 15 and 60 years.
      Since the lifetime risk of germ cell tumor is believed to be higher in patients
      with cryptorchidism than in the general population, the lifetime risk of eventual
      death from germ cell tumor in the cryptorchid population was calculated by
      multiplying each 5-year lifetime risk by 9.7, which is the generally accepted
      relative risk of germ cell tumor in a cryptorchid testis. Contemporary literature
      on perioperative mortality was reviewed and we estimated the current mortality of
      orchiectomy based on American Society of Anesthesiologists (ASA) class. Mortality
      rates were plotted to determine the age when operative mortality exceeds the risk
      of mortality from germ cell malignancy. RESULTS: While perioperative mortality
      and germ cell neoplasia mortality decreased in the last 25 years, the relative
      decrease in perioperative mortality was significantly greater. Thus, in ASA class
      I or II cases mortality from orchiectomy began to exceed mortality from germ cell
      cancer at age 50 years. CONCLUSIONS: Improvements in therapy for germ cell
      neoplasia and perioperative care in the last 25 years have dramatically decreased
      the mortality of each cause. However, the decrease in perioperative mortality has
      been greater. In contrast to a generation ago, accidental death during routine
      elective surgery is now extremely rare in healthy patients. Thus, we advocate
      orchiectomy in all healthy males (ASA I and II) who present with postpubertal
      cryptorchidism until age 50 years.

PMID- 11832726
TI  - Factors predisposing to urinary tract infection after J ureteral stent insertion.
AB  - PURPOSE: We determined the group of patients most likely to have bacterial
      infection or colonization of J stents inserted to relieve ureteral obstruction.
      MATERIALS AND METHODS: Midstream urine from 250 consecutive patients who required
      indwelling J stent insertion obtained before stent insertion and on the day of
      stent removal was analyzed by microbiological testing. At stent removal 3 to 5
      cm. of the stent tip located inside the bladder was also sent for culture.
      Patient sex, duration of stent insertion and systemic disease, such as diabetes
      mellitus, chronic renal failure or diabetic nephropathy, were recorded. Patients
      without systemic disease were classified as normal. The rates of bacteriuria,
      stent colonization and symptomatic urinary tract infection were compared in
      patients with and without systemic disease. RESULTS: Of the 250 patients studied
      180 (72%) were men and 70 (28%) were women, while 152 (60.8%) had no systemic
      disease, 27 (10.8%) had diabetes mellitus, 53 (21.1%) had chronic renal failure
      and 18 (7.2%) had diabetic nephropathy. The bacteriuria rate was 4.2% for stents
      removed within 30 days and 34% for stents removed after 90 days (p <0.001).
      Overall the bacteriuria rate in women was 24.3% compared with 13.9% in men (p
      <0.06). The rate of bacteriuria in normal patients was significantly lower (3.3%)
      than in patients with diabetes mellitus, chronic renal failure and diabetic
      nephropathy (33.3%, 39.6% and 44.4%, respectively, p <0.001). The colonization
      rate of the tip of the stent was higher in women (64.3%) than in men (34.7%). The
      stent was removed prematurely in 9 of the 250 patients (3.6%) because of
      septicemia, including 7 women (77.8%) with systemic disease. CONCLUSIONS: The
      risk of bacteriuria and colonization of the J stent tip is significantly enhanced
      by the duration of stent retention, patient sex and the systemic disease, such as
      diabetes mellitus, chronic renal failure and diabetic nephropathy. These
      categories of patients should undergo shorter stent retention, antimicrobial
      prophylaxis and careful followup to minimize infectious complications.

PMID- 11832727
TI  - Diurnal cortisol variations and symptoms in patients with interstitial cystitis.
AB  - PURPOSE: Little attention has focused on systemic factors that may allow a state
      of chronic bladder inflammation to be established and maintained in interstitial
      cystitis cases. Abnormalities of the hypothalamic-pituitary-adrenal feedback
      system result in poorer regulation of the inflammatory response and are present
      in many chronic inflammatory and pain conditions, of which some have high co
      morbidity with interstitial cystitis. MATERIALS AND METHODS: A total of 48
      patients with interstitial cystitis and 35 healthy, age matched controls
      collected 24-hour urine samples and 3 days of salivary samples at 7 to 8 a.m., 4
      to 5 p.m. and 8 to 9 p.m. for cortisol analysis. In addition, they completed a
      concurrent symptom questionnaire. Prospective symptom diaries also were completed
      in the month before sampling. RESULTS: Mean urinary or salivary cortisol did not
      differ in patients and controls. However, patients with interstitial cystitis and
      higher morning cortisol had significantly less pain and urgency, while those with
      higher urinary free cortisol reported less overall symptomatology (p <0.05).
      Relationships with morning cortisol were also observed when controlling for co
      morbid conditions known to be affected by the hypothalamic-pituitary-adrenal
      axis, such as fibromyalgia, chronic fatigue and rheumatoid arthritis. Patients
      with morning cortisol less than 12.5 nmol./l. were 12.8 times more likely to
      report high urinary urgency than those with values above this cutoff.
      CONCLUSIONS: These findings imply that regulation of the hypothalamic-pituitary
      adrenal axis may be associated with interstitial cystitis symptomatology and
      there may be different diurnal hypothalamic-pituitary-adrenal patterns in
      patients with interstitial cystitis who do and do not have co-morbid conditions.
      These findings may have treatment implications for patients with interstitial
      cystitis who have early morning cortisol deficiencies.

PMID- 11832728
TI  - Noninvasive measurement of bladder pressure by controlled inflation of a penile
      cuff.
AB  - PURPOSE: A noninvasive test providing reliable objective quantification of
      bladder pressure during the voiding cycle would make an important contribution to
      the management of lower urinary tract symptoms. We developed a new noninvasive
      test to measure bladder pressure in males based on controlled inflation of a
      penile cuff during voiding. We compared the new technique with simultaneous
      invasive bladder pressure measurement. MATERIALS AND METHODS: We evaluated 7
      volunteers and 32 patients. A conventional pressure flow study was performed
      first. The bladder was refilled, a penile cuff was fitted and after voiding
      commenced the cuff was inflated in steps of 10 cm. water every 0.75 seconds until
      urine flow was interrupted. The cuff was rapidly deflated, allowing flow to
      resume, and the cycle was repeated until the end of voiding. The flow rate was
      graphed against cuff pressure for each interruption cycle to determine the
      pressure at which flow was interrupted. This pressure was compared with
      simultaneous invasive isovolumetric bladder pressure. RESULTS: Invasive and
      noninvasive pressure measurements agreed well. Average cuff pressure at
      interruption of flow exceeded mean simultaneous isovolumetric bladder pressure
      plus or minus standard deviation by 14.5 +/- 14.0 cm. water. CONCLUSIONS: The new
      method provides noninvasive quantitative information on voiding bladder pressure
      in males. Further study is required to assess whether the technique can
      contribute to the management of lower urinary tract symptoms.

PMID- 11832729
TI  - Maximum urethral closure pressure and sphincter volume in women with urinary
      retention.
AB  - PURPOSE: In 1988 a syndrome of isolated urinary retention in young women that is
      associated with electromyographic abnormality of the striated urethral sphincter
      was described. It was hypothesised that urinary retention resulted from a failure
      of sphincter relaxation. The electromyographic abnormality causes overactivity of
      the muscle and may induce changes of work hypertrophy. If the hypothesis that the
      electromyographic abnormality is the cause of urinary retention is correct, we
      would expect the urethral sphincter to be enlarged and the urethral pressure
      profile to be increased in these women. We evaluated the role of static urethral
      pressure profilometry and transvaginal ultrasound in women in urinary retention.
      MATERIALS AND METHODS: A total of 66 women in complete or partial urinary
      retention underwent electromyography of the striated urethral sphincter using a
      concentric needle electrode, followed by urethral pressure profile and/or
      urethral sphincter volume measurement by transvaginal ultrasound. RESULTS:
      Maximum urethral closure pressure plus or minus standard deviation was
      significantly increased in patients with versus without the electromyographic
      abnormality (103 +/- 26.4 versus 76.7 +/- 18.4 cm. water, p <0.001). Maximum
      urethral sphincter volume was also increased in women with versus without the
      abnormality (2.29 +/- 0.64 versus 1.62 +/- 0.32 cm.3, p <0.001). CONCLUSIONS: The
      results of this study are consistent with the hypothesis that a local sphincter
      abnormality is the cause of urinary retention in a subgroup of women. Urethral
      pressure profilometry and sphincter volume measurement are useful for assessing
      these cases, especially when sphincter electromyography is not readily available.

PMID- 11832730
TI  - Dynamic magnetic resonance imaging of the female pelvis: the relationship with
      the Pelvic Organ Prolapse quantification staging system.
AB  - PURPOSE: Magnetic resonance imaging (MRI) was performed to determine anatomical
      correlations with respect to physical examination using the Pelvic Organ Prolapse
      (POP) staging system. In addition, the standard POP staging system was analyzed
      to obtain normative data and determine any risk factors for prolapse. MATERIALS
      AND METHODS: A total of 52 continent women 19 to 67 years old participated in our
      study. Pelvic MRI was performed at 1.5 Tesla. The vagina, bladder and rectum were
      opacified. Subjects performed pelvic floor contraction, relaxation and straining
      maneuvers for T1-weighted imaging. One-way analysis of variance, Fisher's exact
      test and multinomial logistic regression were used to analyze the data. RESULTS:
      POP stage is quantified from 0 to IV. Stage was 0 to II in 56%, 27% and 17% of
      cases. POP stage was not significantly influenced by the number of cesarean
      sections (p = 0.64) or smoking (p = 0.91) but the number of vaginal deliveries
      significantly correlated with stage. Women with 1 vaginal delivery were at
      increased risk for a stage I condition (p = 0.018), whereas those with more than
      1 were at increased risk for stage II (p = 0.013). On MRI stages 0 versus I or II
      differed significantly in regard to bladder descent (p = 0.01 and <0.0001,
      respectively), while stages 0 versus I differed in regard to levator angle (p =
      0.007). No significant staging differences were observed in regard to the
      posterior urethrovesical angle or stages I versus II with respect to all 3 MRI
      measurements. CONCLUSIONS: MRI appears to detect anatomically measurable changes
      in POP stage 0 versus other stages in regard to bladder descent and the levator
      angle and yet it is not sensitive enough to detect differences in stages I and
      II. It is not unusual for continent women to have a moderate degree of pelvic
      prolapse and previous vaginal delivery appears to increase this risk.

PMID- 11832731
TI  - Intermediate term failure of pubovaginal slings using cadaveric fascia lata: a
      case series.
AB  - PURPOSE: The pubovaginal sling procedure using autologous fascia has become the
      gold standard for treating intrinsic sphincter deficiency and stress urinary
      incontinence in women. A recent modification has been the use of cadaveric fascia
      as the sling material. We recently reported similar results for cadaveric fascia
      lata in 121 women and autologous fascia lata in 46 at a mean followup of 12
      months. We have now identified 8 patients who experienced intermediate term
      failure at 4 to 13 months using cadaveric fascia lata. MATERIALS AND METHODS: We
      retrospectively reviewed the records of 8 of 121 patients who received a
      pubovaginal sling using cadaveric fascia lata between February 1997 and June 1999
      and had recurrent stress incontinence after 4 to 13 months. We reviewed the type
      of fascia, surgical technique, preoperative and postoperative urodynamics,
      surgical history and medical co-morbidities. RESULTS: We identified 8 patients
      who underwent a pubovaginal sling using cadaveric fascia lata and had recurrent
      stress urinary incontinence at a mean of 6.5 months (range 4 to 13) after the
      procedure. Fresh frozen fascia from a local tissue bank was used and the surgical
      technique was identical in all cases. Postoperatively urodynamics confirmed
      recurrent intrinsic sphincter deficiency. Previous incontinence surgery had been
      done in 7 of the 8 patients. Patient co-morbidities included neurological
      disease, diabetes mellitus, previous pelvic irradiation and previous pelvic
      surgery. CONCLUSIONS: We identified a higher than expected intermediate term
      failure rate using fresh frozen cadaveric fascia lata. This risk must be weighed
      against the advantages of decreased operative time and patient morbidity. Longer
      followup and larger numbers are necessary to determine how much of a problem
      exists and what patient characteristics are relevant when selecting cadaveric
      grafts.

PMID- 11832732
TI  - Reliability and validity of the Malay version of the International Prostate
      Symptom Score in the Malaysian population.
AB  - PURPOSE: We validated the Malay version of the International Prostate Symptom
      Score in patients with and without urinary symptoms in the Malaysian population.
      MATERIALS AND METHODS: Validity and reliability were studied in patients with and
      without lower urinary tract symptoms. Reliability was evaluated using the test
      retest method and internal consistency was assessed by Cronbach's alpha.
      Sensitivity to change was expressed as the effect size in the pre-intervention
      versus post-intervention score in additional patients with lower urinary tract
      symptoms who underwent transurethral prostate resection. RESULTS: Internal
      consistency was excellent. A high degree of internal consistency was observed for
      each of the 7 items and for the total score (Cronbach's alpha 0.53 and greater,
      and 0.68, respectively). The test-retest correlation coefficients of the 7 items
      were highly significant. The intraclass correlation coefficient was high at 0.51
      and greater. There was a high degree of sensitivity and specificity to the
      effects of treatment. Significant change from baseline to posttreatment scores
      was observed in all 8 items in the treated but not in the control group.
      CONCLUSIONS: The Malay International Prostate Symptom Score is a suitable,
      reliable, valid instrument that is sensitive to clinical change in the Malaysian
      population.

PMID- 11832733
TI  - Prevalence and correlates of prostatitis in the health professionals follow-up
      study cohort.
AB  - PURPOSE: Prostatitis is an ill-defined condition whose symptoms overlap with
      benign prostatic hyperplasia (BPH). Little is known about the prevalence and
      correlates of prostatitis, or factors that distinguish prostatitis from BPH. We
      examined these issues in a large, nationwide sample of healthy men. MATERIALS AND
      METHODS: In 1992, 31,681 United States health professionals without prostate
      cancer provided information on urological diagnoses, lower urinary tract
      symptoms, and demographic, clinical and lifestyle factors. We calculated age
      adjusted odds ratios and 95% confidence intervals for these correlates predicting
      a history of prostatitis. We also compared characteristics of men with
      prostatitis to those with BPH. RESULTS: The prevalence of a self-reported history
      of prostatitis was 16%. Men reporting a history of BPH had 7.7-fold greater odds
      of a history of prostatitis, those with moderate or severe lower urinary tract
      symptoms had 1.8 and 2.8-fold greater odds, respectively, those with a history of
      sexually transmitted disease had 1.8-fold greater odds and those reporting stress
      at home or work had 1.5- and 1.2-fold greater odds, respectively. The 2,163 men
      with prostatitis alone were younger and had less severe urinary tract symptoms
      (but a similar pattern of symptoms) than the 4,575 men with BPH alone.
      CONCLUSIONS: Self-reported prostatitis was common among healthy men of all ages
      but there was considerable overlap with self-reported BPH. Prostatitis had
      several identifiable correlates that may aid in its recognition.

PMID- 11832734
TI  - Corporoplasty using tunica albuginea free grafts for penile curvature: surgical
      technique and long-term results.
AB  - PURPOSE: A Nesbit or plication procedure for correcting penile deformities is
      associated with penile shortening, especially in patients with excessive
      curvature and/or rotation. On the other hand, grafting procedures are associated
      with poor postoperative results due to graft shrinkage and veno-occlusive
      dysfunction. To minimize penile shortening and preserve potency we describe a new
      surgical technique combining the Nesbit procedure with tunica albuginea free
      grafting. Long-term functional results and patient satisfaction are reported.
      MATERIALS AND METHODS: We treated 17 potent patients with a mean age plus or
      minus standard deviation of 46.1 +/- 14.5 years, including 4 with congenital
      penile deviation and 13 with stabilized Peyronie's disease. Opposite the point of
      maximal curvature a typical Nesbit procedure was performed. The excised tunica
      albuginea segment consequently served as a free graft. A symmetrical incision was
      made at the opposite site and the preserved elliptical tunica albuginea graft was
      placed in the defect. Further elliptical excisions and grafting followed as
      needed to correct the deformity. RESULTS: At a mean followup of 39.5 +/- 13.7
      months (range 18 to 62) all patients reported penile straightening and functional
      erection, while ultrasonography of the corpora cavernosa revealed no changes in
      graft ultrastructure. There was penile shortening in 8 patients (47%) but only 2
      (11.7%) considered it significant. All patients with a minimum 2-year followup
      were positive in regard to recommending the operation to others or repeating it
      if necessary. CONCLUSIONS: The newly described technique may be considered as a
      treatment option in patients with excessive penile curvature since shortening of
      the penile shaft is eliminated by 50% compared with the result of the Nesbit
      procedure. Tunica albuginea seems to be an appropriate grafting material since it
      prevents postoperative corporeal veno-occlusive dysfunction.

PMID- 11832735
TI  - Erectile dysfunction after radical prostatectomy: hemodynamic profiles and their
      correlation with the recovery of erectile function.
AB  - PURPOSE: Despite the advent of nerve sparing radical prostatectomy some men
      experience erectile dysfunction. Many of these men have vasculogenic erectile
      impairment in the form of arterial insufficiency or venous leakage. Recent data
      imply that early postoperative injection therapy may decrease the rate of
      erectile dysfunction. We defined hemodynamic patterns in patients who underwent
      bilateral nerve sparing radical prostatectomy to assess the chronology of venous
      leakage development and explore the correlation of hemodynamic profiles with the
      return of functional erection 12 months postoperatively. MATERIALS AND METHODS:
      Patients with excellent preoperative erectile function who underwent bilateral
      nerve sparing surgery and had no pharmacological support for erectile dysfunction
      in the initial 12 months after surgery received vascular evaluation at
      presentation. Vascular evaluation involved cavernosometry or penile
      ultrasonography. Patients were then interviewed again at least 12 months
      postoperatively to assess the ability to achieve sexual intercourse. RESULTS: Our
      study group comprised 96 men with a mean age plus or minus standard deviation of
      54 +/- 12 years who met all inclusion criteria. All patients had pathologically
      proved organ confined disease. Mean time to the initial postoperative
      presentation was 6 +/- 5 months. Patients were divided into 4 groups according to
      the time of vascular studies postoperatively, namely less than 4 to 8, 9 to 12
      and greater than 12 months. Normal vascular status, arterial insufficiency and
      venous leakage were diagnosed in 35%, 59% and 26% of the group, respectively. No
      difference in the incidence of arterial insufficiency was noted in the 4 time
      groups. Time postoperatively was significantly associated with the incidence of
      venous leakage (14% at less than 4 months and 35% at between 9 and 12). In regard
      to the correlation of the vascular diagnosis with the return to functional
      erection 47% of the normal, 31% of the arteriogenic and 9% of the venous leakage
      group achieved sexual intercourse 12 months postoperatively. CONCLUSIONS: These
      data imply that the longer the duration of erectile dysfunction after radical
      prostatectomy, the greater the risk of venous leakage. Furthermore, it appears
      that the prognosis for the return of functional erection is worst when venous
      leakage is present.

PMID- 11832736
TI  - Hydrophilic guide wire technique to facilitate organ entrapment using a
      laparoscopic sack during laparoscopy.
AB  - PURPOSE: Morcellation of the kidney in a LapSac (Cook Surgical, Spencer, Indiana)
      is reportedly safe and effective during laparoscopic nephrectomy. However, organ
      entrapment in a LapSac can be difficult, especially during early surgeon
      experience. A technique to facilitate organ entrapment is described. MATERIALS
      AND METHODS: We have recently used a simple technique to facilitate deployment of
      the LapSac in the abdomen using a hydrophilic nitinol guide wire passed through
      the holes in the mouth of the sack beside its drawstring. The inherent elasticity
      of the guide wire helps to spring open the mouth of the sack, while facilitating
      appropriate orientation of the sack mouth. RESULTS: This technique appears to
      decrease the time needed for organ entrapment because it eliminates the need to
      triangulate the sack to achieve organ entrapment. An additional port is usually
      not required during the procedure. CONCLUSIONS: The hydrophilic guide wire
      technique is inexpensive and effective for LapSac deployment and organ
      entrapment.

PMID- 11832737
TI  - Laparoscopic pyeloplasty with concomitant pyelolithotomy.
AB  - PURPOSE: We present our experience with laparoscopic pyeloplasty plus
      pyelolithotomy in patients in whom stones were not the cause of ureteropelvic
      junction obstruction. MATERIALS AND METHODS: A transperitoneal approach was used
      for laparoscopic pyeloplasty and pyelolithotomy in 19 patients (20 renal units).
      Before ureteropelvic junction repair stones were extracted through a small
      pyelotomy that was eventually incorporated into the final pyeloplasty incision.
      Stones in the renal pelvis were removed with rigid graspers under direct
      laparoscopic vision. A flexible cystoscope introduced through a port was used to
      extract stones in the calices. The renal pelvis was reconstructed based on the
      anatomy of the ureteropelvic junction. RESULTS: A median of 1 stone (range 1 to
      28) was recovered. In 11, 8 and 1 patients the Anderson-Hynes dismembered
      pyeloplasty, Y-V plasty and the Heinecke Mickulicz procedure were performed,
      respectively. At 3 months 2 patients had residual calculi for a procedural stone
      free rate of 90%. There was no evidence of obstruction in 18 of the 20 cases
      (90%), as confirmed by negative diuretic scan or radiological improvement of
      hydronephrosis. At a mean followup of 12 months (range 3 to 57) 2 additional
      patients had recurrent stones for an overall long-term stone-free rate of 80% (16
      of 20). CONCLUSIONS: Laparoscopic pyelolithotomy is feasible when combined with
      pyeloplasty. Our results are comparable to those of stone removal during open
      pyeloplasty or percutaneous endopyelotomy. The advantages of open surgery appear
      to be maintained in this minimally invasive approach.

PMID- 11832738
TI  - Curvature correction in patients with tunical rupture: a necessary adjunct to
      repair.
AB  - PURPOSE: We review our experience with traumatic tunical rupture repair with and
      without simultaneous penile curvature correction. MATERIALS AND METHODS: Since
      November 1987, 11 men 23 to 39 years old have presented to us with tunical
      rupture, of whom 10 underwent surgical repair. All except 1 of the 8 men injured
      during sexual activity reported a curved penile appearance during erection. After
      patient 3 in our series sustained repeat rupture 5 months postoperatively due to
      penile curvature the next 7 underwent simultaneous curvature correction, which
      since 1996 has been done using 6-zero nylon. RESULTS: Recovery was uneventful in
      2 of the 3 men who underwent simple tunical repair with 4-zero polyglactin or
      polyglycolic acid. All 7 of subsequent patients in whom curvature correction was
      performed simultaneously recovered satisfactorily with resumed erectile
      capability. CONCLUSIONS: Although coital position may be an important factor in
      tunical rupture during sexual activity, penile curvature may be contributory and
      should be corrected simultaneously with tunical repair.

PMID- 11832739
TI  - Nelfinavir urinary stones.

PMID- 11832740
TI  - Pure laparoscopic enterocystoplasty.

PMID- 11832741
TI  - Rapid resolution of carbon dioxide pneumothorax (capno-thorax) resulting from
      diaphragmatic injury during laparoscopic nephrectomy.

PMID- 11832742
TI  - End-to-end reconstruction of synchronous urethral strictures.

PMID- 11832743
TI  - Massive adrenocortical adenoma following long-term treatment of 21-hydroxylase
      deficiency.

PMID- 11832744
TI  - Progressive sclerosis of isolated foot metastasis of prostate cancer.

PMID- 11832745
TI  - Intraperitoneal rupture of giant hydronephrosis due to ureteral cancer
      accompanied by renal cell carcinoma.

PMID- 11832746
TI  - Renal cell carcinoma induced Coombs negative autoimmune hemolytic anemia and
      severe thrombocytopenia responsive to nephrectomy.

PMID- 11832747
TI  - Renal carcinoma after laparoscopic cyst decortication.

PMID- 11832748
TI  - Primary Burkitt's lymphoma of bladder in patient with AIDS.

PMID- 11832750
TI  - Endosalpingiosis of bladder.

PMID- 11832749
TI  - Recurrent bladder leiomyoma with ovarian steroid hormone receptors.

PMID- 11832751
TI  - Female paraurethral leiomyoma: immunohistochemical approach to the relationship
      between leiomyoma and ovarian hormones.

PMID- 11832752
TI  - Re: Strategies for transplantation of cadaveric kidneys with congenital fusion
      anomalies.

PMID- 11832753
TI  - Re: The stone cone: a new generation of basketry.

PMID- 11832754
TI  - Re: Urine based markers of urological malignancy.

PMID- 11832756
TI  - Re: Microsurgical denervation of the spermatic cord as primary surgical treatment
      of chronic orchialgia.

PMID- 11832755
TI  - Re: Combined stent and artificial urinary sphincter for management of severe
      recurrent bladder neck contracture and stress incontinence after prostatectomy: a
      long-term evaluation.

PMID- 11832758
TI  - Vesico-ureteral reflux in the paraplegic: cause and correction. 1952.

PMID- 11832759
TI  - An operative technique for the correction of vesicoureteral reflux. 1958.

PMID- 11832761
TI  - Heredity of hypospadias and the significance of low birth weight.
AB  - PURPOSE: We analyzed a large group of patients with hypospadias regarding
      familial aggregation, phenotype, twin rate and ethnic origin and assessed the
      correlation of low birth weight with hypospadias. MATERIALS AND METHODS: We
      mailed questionnaires to 2,503 boys operated on for hypospadias in Sweden asking
      for additional cases of hypospadias in the family, the number of brothers in the
      nuclear family, and birth weight of the boys with hypospadias and their brothers.
      RESULTS: Of the boys 7% reported 1 or more additional family members with
      hypospadias. The birth weight of the boys with hypospadias was significantly
      lower (p = 5 x 10-13) than the birth weight of their unaffected brothers.
      Phenotyping of 676 individuals revealed glandular hypospadias in 53%, penile
      forms in 39%, penoscrotal or perineal variants in 6% and cleaved prepuce as the
      only manifestation in 2%. There were 50% more twins than expected compared to the
      general population and established zygosity in 83% (67% monozygotic, 33%
      dizygotic). Non-Swedish ethnicity was noted in 22% of the subjects, a third of
      whom were from Middle Eastern countries. CONCLUSIONS: We present data on
      heredity, birth weight, phenotype and ethnic origin in a large group of patients
      with hypospadias. The finding of additional members with hypospadias in 7% of the
      families supports the concept that genetic factors are involved in the
      pathogenesis. The strong association with low birth weight may be explained by
      genetic and environmental factors.

PMID- 11832762
TI  - Contrast enhanced reflux sonography in children: a comparison to standard
      radiological imaging.
AB  - PURPOSE: The diagnosis of vesicoureteral reflux is routinely performed by voiding
      cystourethrography. Especially in the course of conservative treatment, the
      radiation dose might increase during the years. With the development of
      ultrasound echo enhancing agents we assessed their diagnostic efficacy for
      evaluation of vesicoureteral reflux to replace voiding cystourethrography with
      radiation-free ultrasound. MATERIALS AND METHODS: A total of 104 children with a
      mean age of 5.4 years were examined using echo enhancing ultrasound after
      informed consent was obtained. For control purposes, all children underwent
      standard voiding cystourethrography as well. The diagnosis of vesicoureteral
      reflux was positive when microbubbles appeared in the ureter or renal pelvis. The
      sonographic findings were correlated with those obtained by standard voiding
      cystourethrography. RESULTS: Of the 208 ureter and renal units investigated
      vesicoureteral reflux was detected in 76 (37%) by both technologies. Diagnosis
      was made sonographically in 5 units and by voiding cystourethrography in 3. All
      reflux grades (I to V) could be identified. The specificity and sensitivity of
      the contrast reflux ultrasound were significantly high. The long contrast time of
      up to 30 minutes combined with the high contrast effect resulted in convincing
      images with high levels of diagnostic confidence. CONCLUSIONS: Our results
      clearly demonstrate that the diagnostic accuracy of vesicoureteral reflux by
      contrast enhanced ultrasound is statistically significant compared to standard
      radiological voiding cystourethrography. Therefore, this methodology represents
      an exceptional approach to reduce the number of children being exposed to
      ionizing radiation especially during conservative followup.

PMID- 11832763
TI  - Xanthogranulomatous pyelonephritis in a dysplastic kidney with reflux associated
      with posterior urethral valves.

PMID- 11832764
TI  - Progressive Langerhans' cell histiocytosis presenting as a primary penile lesion.

PMID- 11832765
TI  - Reduced number of glomeruli in kidneys with neonatally induced partial
      ureteropelvic obstruction in pigs.
AB  - PURPOSE: We quantify the structural components of the nephron in adult pig
      kidneys with neonatally induced unilateral hydronephrosis in comparison with
      nonobstructed kidneys. MATERIALS AND METHODS: The study included 11 pigs with
      unilateral partial ureteropelvic obstruction induced 2 days after birth and 8
      sham operated control pigs. Obstructed kidney glomerular filtration rate was
      significantly reduced at age 4 weeks but did not differ from control kidneys
      after 24 weeks. At age 24 weeks the kidneys were perfusion fixed, and the number
      and volume of glomeruli and tubular lengths were measured using stereological
      methods. RESULTS: Mean obstructed kidney volume did not differ from that of
      control kidneys. Mean number plus or minus standard deviation of glomeruli in the
      obstructed kidneys was reduced by 28% compared to that of control kidneys (502 +/
      163 x 103 versus 697 +/- 161 x 103, p = 0.02), whereas no difference in mean
      glomerular volume was observed. Mean length of the proximal or distal tubules did
      not differ between obstructed and control kidneys. Mean number or volume of
      glomeruli in nonobstructed kidneys contralateral to obstructed kidneys did not
      differ from that of control kidneys. The individual number of glomeruli in the
      obstructed kidneys was not associated with function of these kidneys.
      CONCLUSIONS: Neonatally induced unilateral partial ureteropelvic obstruction
      causes impaired nephrogenesis with a significant reduction in the number of
      nephrons, which is not reflected in measurements of kidney function in this
      model. The reduction in the number of glomeruli suggests that congenital
      unilateral obstruction impairs nephrogenesis.

PMID- 11832766
TI  - Is endoscopic decompression of the neonatal extravesical upper pole ureterocele
      necessary for prevention of urinary tract infections or bladder neck obstruction?
AB  - PURPOSE: It has been hypothesized that endoscopic decompression of the duplex
      extravesical ureterocele is necessary to prevent the complications of urinary
      tract infections and progressive hydronephrosis. This study was performed to test
      this premise. MATERIALS AND METHODS: Infants younger than 2 weeks with an
      extravesical ureterocele associated with a duplex upper pole moiety were assigned
      to immediate endoscopic puncture of the ureterocele followed by antibiotic
      prophylaxis or antibiotic prophylaxis with plans for delayed surgical
      intervention. Radiographic studies and catheterized urine cultures were obtained
      at ages 3 and 6 months and for fever greater than 38.5C. All patients included in
      this study were followed through 6 months of life. RESULTS: Of the patients 32
      underwent endoscopic puncture of the ureterocele. Median patient age at endoscopy
      was 5 days (range 3 to 13). During the first 6 months of life complications
      developed in 4 (12%), including febrile urinary tract infections in 3 (9%) and
      with progressive hydronephrosis due to incomplete puncture of the ureterocele in
      1 (3%). The remaining 40 patients were treated with antibiotic prophylaxis and
      delayed open surgery. Median time to open surgery was 3 months (range 2 to 6).
      During the first 6 months of life complications developed in 5 (13%), including 3
      (8%) febrile urinary tract infections and progressive hydronephrosis in 2 (5%).
      No statistical difference was noted between the 2 treatment groups. CONCLUSIONS:
      In patients with extravesical duplex ureteroceles neonatal complications of
      urinary tract infection and progressive hydronephrosis are not significantly
      different between those treated with immediate endoscopic decompression versus
      delayed open surgical intervention.

PMID- 11832767
TI  - Endoscopic treatment of vesicoureteral reflux: 11 to 17 years of followup.
AB  - PURPOSE: We review our 17-experience with endoscopic subureteral
      polytetrafluoroethylene injection for the treatment of primary vesicoureteral
      reflux in children. MATERIALS AND METHODS: We retrospectively reviewed the charts
      of 258 patients with primary vesicoureteral reflux who were treated with
      subureteral polytetrafluoroethylene injection from 1984 to 1990. RESULTS: The
      study included 205 girls and 53 boys between 3 months and 14 years old (median
      age 6 years). Of the patients 92 had unilateral vesicoureteral reflux, 129 had
      bilateral reflux and 37 had a refluxing duplex system including 6 with bilateral
      duplex systems. Endoscopic treatment by subureteral polytetrafluoroethylene
      injection was performed in 393 ureters. Reflux was corrected in 302 ureters
      (76.8%) after a single injection. Injection failed to stop reflux in 7 ureters (7
      patients) and reimplantation was required. Patients were followed from 11 to 17
      years with a mean followup plus or minus standard deviation of 13.5 +/- 3.4
      years. Four patients were either lost to followup or parents refused to let them
      undergo voiding cystourethrography. Voiding cystourethrography in 247 patients
      with 379 ureters revealed that 360 ureters (95%) remain free of reflux whereas
      reflux recurred in 19 ureters (5%). Of these 19 ureters reflux was grade I or II
      in 13 for which no treatment was given and reflux was grade III or IV in 6, which
      required repeat injection. No untoward effects were seen in any of these patients
      with use of polytetrafluoroethylene as an injectable biomaterial. CONCLUSIONS:
      Endoscopic subureteral polytetrafluoroethylene injection is a simple and
      effective outpatient procedure for in the treatment of vesicoureteral reflux. No
      long-term morbidity was observed in our patients with small amounts of injectable
      polytetrafluoroethylene.

PMID- 11832768
TI  - The aquaporin-2 water channel in autosomal dominant primary nocturnal enuresis.
AB  - PURPOSE: Nocturnal enuresis is one of the most common diagnoses in a pediatric
      clinic. Recently, linkage analysis revealed a 2-point lod score of 4.2 in 6
      families with dominant primary nocturnal enuresis around the aquaporin-2 (AQP2)
      water channel locus. Since primary nocturnal enuresis is ameliorated by
      desmopressin, AQP2 expression is increased by desmopressin and AQP2 is essential
      for concentrating urine, we determined whether a mutation in the AQP2 gene could
      cause primary nocturnal enuresis in these families. MATERIALS AND METHODS:
      Genomic DNAs of several patients from the 6 families were analyzed for disease
      causing mutations in the 4 exons of the AQP2 genes. RESULTS: In 1 family a G to A
      transition in the intron 1 splice donor site was found but it was also found in
      healthy subjects. In another family a C to T transition in the intron 1 splice
      acceptor region was identified but it was often found in splice acceptor sites.
      In 2 families a C to T transition was identified in the coding region of exon 3
      but this mutation did not lead to a changed amino acid. CONCLUSIONS: Since no
      mutation in the AQP2 coding sequence was found, while this is essential for
      involvement in dominant primary nocturnal enuresis, the AQP2 gene is excluded as
      a candidate for autosomal dominant PNE in these families in which the disease co
      segregates with chromosome 12q.

PMID- 11832769
TI  - Are aquaporin water channels the "holy grail" of primary nocturnal enuresis?

PMID- 11832770
TI  - Guanosine phosphate binding protein coupled receptors in prostate cancer: a
      review.
AB  - PURPOSE: Androgens are the primary growth promoters of the prostate gland and yet
      prostate tumors progress despite androgen ablation. This progression suggests a
      role for additional cellular factors in the progression to androgen independent
      disease. We examined the role of a family of extracellular signal regulators,
      namely the guanosine phosphate binding (G) protein coupled receptor (GPCR)
      family, in prostate cancer. MATERIALS AND METHODS: A comprehensive review of the
      literature was performed on GPCRs and prostate cancer, and supplemented with
      published and unpublished observations made at our laboratory. Emphasis was
      placed on the mechanistic aspects of mitogenic signaling pathways involved to
      identify potential targets for therapy. RESULTS: Expression of some GPCRs and
      GPCR ligands is elevated in prostate cancer cells and adjacent prostatic stromal
      tissue. In vitro studies demonstrate that activation of GPCRs confers a distinct
      growth and survival advantage on prostate cancer cells, including enhanced
      proliferation and decreased programmed cell death (apoptosis). Specifically
      stimulation of GPCRs for lysophosphatidic acid and bradykinin induces
      proliferation of androgen independent prostate cancer cells via the activation of
      the extracellular signal regulated kinase (ERK) pathway. Induction of ERK by the
      bradykinin and lysophosphatidic acid in prostate cells proceeds via distinct
      pathways and involves Galphaq and Gbetagamma subunits, respectively. The
      Gbetagamma dependent activation of ERK requires tyrosine kinases, including
      epidermal growth factor receptor and c-Src. Furthermore, stimulation with LPA
      enhances the survival of prostate cancer cells via activation of the inducible
      transcription factor nuclear factor-kappaB. CONCLUSIONS: GPCR stimulation induces
      proliferation and prevents apoptosis of hormone independent prostate cancer
      cells, indicating their important role in the progression of prostate cancer.
      While further confirmatory studies are required to verify the role of GPCRs in
      disease progression, the therapeutic implications of these studies may enhance
      the armamentarium in the fight against prostate cancer.

PMID- 11832771
TI  - Allelic loss on chromosomes 8 and 9 correlates with clinical outcome in locally
      advanced clear cell carcinoma of the kidney.
AB  - PURPOSE: We correlated allelic loss on chromosomes 8p, 9p and 14q with clinical
      outcome in locally advanced conventional renal cell carcinoma. MATERIALS AND
      METHODS: We analyzed radical nephrectomy specimens from 72 stage P3N0
      conventional renal cell carcinomas by microsatellite loss of heterozygosity (LOH)
      analyses directed at chromosomes 3p, 8p, 9p and 14q (2 primers per chromosome).
      All patients were treated with surgery only. LOH results were correlated with
      disease-free survival using the Kaplan-Meier method. RESULTS: We detected LOH on
      chromosome 3p in 60 of 64 (94%), on chromosome 8p in 19 of 59 (32%), on 9p in 21
      of 67 (31%) and on 14q in 18 of 70 (26%) informative cases. Of the 72 patients 24
      (33%) had recurrence during followup. On univariate analysis patients with tumors
      demonstrating LOH on chromosomes 8p and 9q were at high risk for recurrence (p =
      0.01). The correlation of recurrence with LOH approached significance for the
      individual chromosomes 8p and 9p (p = 0.10 and 0.14, respectively). No
      correlation was observed of LOH on chromosome 14q with recurrence (p = 0.42). The
      correlation of tumor grade with risk of relapse also approached significance (p =
      0.12). On multivariate analysis LOH on chromosome 8p was a more powerful
      predictor of recurrence than tumor grade. When combinations of LOH on chromosomes
      were tested, LOH on chromosomes 8p and 9p was the most powerful predictor of
      recurrence (p = 0.006). CONCLUSIONS: LOH on chromosomes 8p or 9p may provide
      prognostic significance in patients with locally advanced renal cell carcinoma.

PMID- 11832772
TI  - p53 and microvessel density in primary resection specimens of superficial bladder
      cancer.
AB  - PURPOSE: p53 Regulates angiogenesis in fibrosarcoma and correlative studies
      suggest a similar role for muscle invasive bladder cancer. We evaluated the
      associations of p53 status and microvessel density with pathological features and
      clinical outcomes in a large population of patients with superficial bladder
      cancer. In addition, we assessed the correlation of p53 status with microvessel
      density, which would suggest the regulation of angiogenesis by p53. MATERIALS AND
      METHODS: We stained 84 primary bladder resection specimens, including 55 stage
      pTa, 29 stage pT1, 27 grade 1, 35 grade 2 and 22 grade 3 samples, for p53, CD31
      and CD34. The relationships of p53 or microvessel density and tumor stage-grade
      or clinical recurrence-progression were analyzed by analysis of variance and
      pairwise comparison analysis for least significant difference, and Pearson
      correlation coefficients. Only patients with no previous biopsy were included in
      analysis to preclude interference by granulation tissue related
      neovascularization. The 4 samples with significant inflammation were also
      excluded from study. RESULTS: At a mean followup of 33 months (range 1 to 93) 34
      of 84 patients (40.4%) experienced 1 or more tumor recurrences and 10 (11.9%) had
      stage and/or grade progression. Statistically significant associations were
      observed of p53 immunostaining and microvessel density with tumor stage and grade
      (p <0.05). However, the association of p53 status with microvessel density was
      weak and not statistically significant. Similar results were observed for the
      CD31 and CD34 based estimates of microvessel density. Neither p53 status nor
      microvessel density correlated with recurrence or progression. CONCLUSIONS: Our
      study confirms the strong association of p53 and microvessel density with the
      well established prognostic factors of grade and stage in superficial bladder
      cancer, supporting other evidence of an important role for p53 and angiogenesis
      in the tumor biology of this disease. However, our data argue against a primary
      role of p53 in the regulation of angiogenesis in superficial bladder cancer. This
      study, which to our knowledge is the first to focus on primary resection
      specimens, suggests that other genetic or environmental factors may contribute to
      the regulation of angiogenesis in superficial bladder cancer.

PMID- 11832774
TI  - Role of thymidine phosphorylase in an in vitro model of human bladder cancer
      invasion.
AB  - PURPOSE: It has been previously demonstrated that the angiogenic factor thymidine
      phosphorylase is elevated significantly in invasive bladder cancer. We report
      that it is not merely an incidental finding. Thymidine phosphorylase has a
      functional role in bladder cancer invasion. MATERIALS AND METHODS: The
      superficial bladder cancer cell line RT112 was transfected by retroviral
      techniques to generate the RT112-TP clone that expressed significantly elevated
      levels of thymidine phosphorylase, comparable to those of invasive human bladder
      cancers. The empty vector control RT112-EV was generated for comparison. Growth
      of these transfectants was examined using a new in vitro model of bladder cancer
      invasion based on de-epithelialized rat bladder and by assessing growth as
      xenografts in nude mice. The effect of 5-deoxy-5-fluorouridine, a prodrug
      activated by TP to produce 5-fluorouracil, was also examined. RESULTS: RT112-TP
      high thymidine phosphorylase expressing cells invaded into the stroma of the in
      vitro model but wild-type RT112 and RT112-EV cells did not. This invasion was
      abolished by 5-deoxy-5-fluorouridine. Invasion correlated with thymidine
      phosphorylase expression on immunohistochemical testing. There was also a
      significantly greater xenograft growth rate for RT112-TP than for RT112-EV,
      confirming the malignant growth advantage conferred by thymidine phosphorylase.
      CONCLUSIONS: We demonstrated that thymidine phosphorylase may have a functional
      role in bladder cancer invasion and the apparent advantage of thymidine
      phosphorylase expression to tumor cells can be exploited by therapies that
      utilize prodrugs such as 5-deoxy-5-fluorouridine, which is activated by thymidine
      phosphorylase and inhibited invasion in our model.

PMID- 11832773
TI  - Preoperative plasma levels of interleukin-6 and its soluble receptor predict
      disease recurrence and survival of patients with bladder cancer.
AB  - PURPOSE: Elevated levels of interleukin-6 (IL-6) are associated with metastasis
      and poor prognosis in various malignancies. Since the IL-6 soluble receptor (IL
      6sR) potentiates the systemic effects of IL-6, each may independently impact the
      disease process. We tested the hypothesis that preoperative plasma IL-6 and IL
      6sR levels would predict cancer stage and prognosis in patients with transitional
      cell carcinoma of the bladder. MATERIALS AND METHODS: The study group consisted
      of 51 patients who underwent radical cystectomy for transitional cell carcinoma
      and 44 men without cancer. Preoperative plasma levels of IL-6 and IL6sR were
      measured by enzyme-linked immunosorbent assay and correlated with pathological
      features and clinical outcome. RESULTS: IL-6 levels were higher in patients with
      bladder cancer than in healthy controls (p <0.001). In bladder cancer cases
      elevated levels of IL-6 and IL-6sR were associated with adverse pathological
      features, including muscle invasion, lymphovascular invasion and lymph node
      metastases (p <0.05). High levels of IL-6sR were also associated with
      pathological tumor grade (p = 0.036). In separate multivariate models that
      included clinical stage and grade IL-6 and IL-6sR levels were independent
      predictors of lymphovascular invasion, metastases to lymph nodes, disease
      recurrence and disease specific survival (p <0.05). In a preoperative Cox
      proportional hazards model IL-6 (p = 0.050) and IL-6sR (p = 0.035) predicted
      disease specific survival. CONCLUSIONS: We found that plasma IL-6 levels were
      higher in patients with bladder cancer than in healthy controls. Levels of IL-6
      and IL-6sR were associated with cancer stage and metastases, and were strong
      independent predictors of disease recurrence and disease specific survival.

PMID- 11832775
TI  - Detection of beta-human chorionic gonadotropin expressing cells by nested reverse
      transcriptase-polymerase chain reaction in the peripheral blood stem cells of
      patients with advanced germ cell tumor.
AB  - PURPOSE: We investigated whether peripheral blood stem cells (PBSCs) were
      contaminated by tumor cells. MATERIALS AND METHODS: A total of 13 patients with
      advanced testicular cancer underwent PBSC transplantation at our institute.
      Nested reverse transcriptase-polymerase chain reaction using primers specific for
      beta-human chorionic gonadotropin (beta-HCG) or alpha-fetoprotein (AFP) detected
      1 beta-HCG or AFP producing cell in 1 x 10(6) PBSCs. RESULTS: Although AFP
      messenger (m) RNA was not identified in any of the 13 patients, beta-HCG mRNA was
      detected in 7. All patients with beta-HCG mRNA in PBSCs had elevated serum beta
      HCG before treatment. Three patients with a normal beta-HCG range before
      treatment did not have beta-HCG mRNA in the PBSCs. The serum beta-HCG level in
      the patients whose PBSCs were contaminated with tumor cells was significantly
      higher than in patients whose PBSCs contained no tumor cells. Four of the 7
      patients with beta-HCG mRNA in PBSCs eventually died of cancer, whereas those
      whose PBSCs were not contaminated with tumor cells survived without disease.
      CONCLUSIONS: Patients with elevated serum beta-HCG levels are likely to have
      PBSCs contaminated by tumor cells. Moreover, the prognosis of patients with tumor
      cells in the PBSCs is poor.

PMID- 11832776
TI  - In vivo optical coherence tomography feasibility for bladder disease.
AB  - PURPOSE: Optical coherence tomography is a new imaging modality capable of
      imaging luminal surface of biological tissue in the near infrared range with a
      spatial resolution close to the cellular level. We identified characteristic
      optical coherence tomography patterns for nonproliferative and proliferative
      inflammation, and malignant alterations of the bladder. MATERIALS AND METHODS:
      Optical coherence tomography was performed to image the bladder of 66 patients.
      The probe passed through the operating channel of a cystoscope and was pressed
      onto the mucosal site of interest. A mucosal biopsy of the image site was
      obtained. Optical coherence tomography was used to construct 680 images of the
      bladder and the images were compared with histology slides. RESULTS: Optical
      coherence tomography images of normal bladder showed 3 layers, namely the mucosa
      or transitional epithelium, submucosa and smooth muscle. In exudative processes
      there were poor light scattering areas in the connective tissue layer. Images of
      bladders with proliferative cystitis revealed nonuniform thickening of the
      epithelium or hyperplasia. Squamous metaplasia appeared as thicker and less
      transparent epithelium with a jagged boundary. Images of transitional cell
      carcinoma were characterized by the complete loss of a regular layered structure
      of the bladder wall and the penetration depth of optical imaging was slight.
      CONCLUSIONS: This study provides the characteristic optical coherence tomography
      pattern of nonproliferative and proliferative inflammation, and the
      characteristic appearance of severe dysplasia and transitional cell carcinoma.
      This technique may be useful as a guide for biopsy and for assisting in
      establishing resection margins.

PMID- 11832777
TI  - Urinary concentration and tissue messenger RNA expression of monocyte
      chemoattractant protein-1 as an indicator of the degree of hydronephrotic atrophy
      in partial ureteral obstruction.
AB  - PURPOSE: To find a potential prognostic marker of the induction of hydronephrotic
      atrophy in congenital hydronephrosis we investigated whether the messenger (m)RNA
      expression and urinary concentration of monocyte chemoattractant protein-1 (MCP
      1) correlated with the degree of partial ureteral obstruction, and subsequent
      hydronephrotic atrophy and interstitial fibrosis. MATERIALS AND METHODS: We
      created left partial ureteral obstruction in 96 juvenile Wistar rats and complete
      ureteral obstruction in 18, while 16 underwent sham operation. Depending on
      excretion of contrast medium into the renal pelvis after 3 days we defined 2
      degrees of hydronephrosis. Renal mRNA expression of MCP-1, and renal pelvic and
      bladder urinary concentrations of MCP-1 were measured after 1, 2 and 3 weeks, and
      compared with the degree of hydronephrotic atrophy. RESULTS: Grade 1 partial
      ureteral obstruction resulted in mild histological changes. Grade 2 partial and
      complete obstruction resulted in significant hydronephrotic atrophy. MCP-1 mRNA
      expression in the kidney remained unchanged in grade 1 partial obstruction but
      was moderately increased in grade 2 partial obstruction and clearly over
      expressed in complete ureteral obstruction. The renal pelvic urinary
      concentration of MCP-1 was not higher in rats with grade 1 partial obstruction
      than in sham operated animals but it was significantly increased in those with
      grade 2 partial and complete obstruction. CONCLUSIONS: mRNA expression and the
      urinary concentration of MCP-1 correlate with the degree of obstruction and
      subsequent renal damage in hydronephrosis. They may serve as prognostic markers
      in children with congenital hydronephrosis.

PMID- 11832779
TI  - Effects of chronic partial outlet obstruction on blood flow and oxygenation of
      the rat bladder.
AB  - PURPOSE: Experimental partial bladder outlet obstruction in rats and rabbits
      drives the bladder through 3 sequential responses, referred to as hypertrophy,
      compensation and decompensation. The hypertrophy phase, which is a period of
      rapid bladder growth, has previously been shown to be accompanied by a
      significant increase in bladder blood flow in rats and rabbits in a manner that
      likely supports the bladder cell growth process. However, chronic periods of
      obstruction in the rabbit have been shown to reduce significantly bladder blood
      flow, especially to the detrusor smooth muscle, corresponding with a loss of
      bladder contractile function or decompensation in these animals. We determined
      the effects of chronic 1 to 4-week partial outlet obstruction on rat bladder
      blood flow and directly correlated them with hypoxia in the rat bladder.
      MATERIALS AND METHODS: Rats underwent surgical partial bladder outlet obstruction
      under anesthesia. At weekly intervals after surgery relative blood flow to the
      bladder and spleen was measured by a fluorescent microsphere infusion technique.
      Sham operated rats were also studied 2 and 4 weeks following surgery. In a second
      experiment groups of similarly obstructed rats were treated with Hypoxyprobe-1
      (Natural Pharmacia International, Inc., Research Triangle Park, North Carolina),
      a chemical probe for hypoxia, 3 days, 1 and 2 weeks after partial bladder outlet
      obstruction. The bladders were subsequently fixed and immunostained using a
      monoclonal antibody that detects Hypoxyprobe-1 adducts that are selectively
      formed in hypoxic cells. RESULTS: Neither bladder weight nor bladder relative
      blood flow was affected by sham surgery. Likewise, control and sham obstructed
      rat bladders were found to be free of Hypoxyprobe-1 reactive areas. In contrast,
      obstructed rats had significantly increased bladder weight at all time points.
      Relative weight of the obstructed rat bladders indicates the response to mild
      moderate obstruction. Bladder relative blood flow in obstructed rats was
      significantly elevated 1 and 2 weeks after partial bladder outlet obstruction but
      it returned to almost control levels by 3 and 4 weeks. Hypoxyprobe-1 staining
      demonstrated a sequential transition of hypoxia from bladder mucosa and
      submucosal regions at 3 days to muscularis and serosal fibroblasts 1 week and
      finally to smooth muscle cells by 2 weeks after obstruction. CONCLUSIONS: In
      contrast to the rabbit model, global blood flow in the mild-moderate chronically
      obstructed rat bladder was found to be higher or nearly equivalent to blood flow
      in unobstructed control rat bladders. However, even in the presence of normal or
      above normal blood flow focal regions of hypoxia were still observed in
      obstructed rat bladders and these regions changed with time. These results
      provide a reason to understand better why rats are more resistant to the onset of
      bladder decompensation than rabbits and support the concept that hypoxia is
      involved in bladder remodeling as well as in progressive functional impairment of
      the bladder after partial bladder outlet obstruction.

PMID- 11832778
TI  - Plasminogen activator inhibitor-1 and tissue-type plasminogen activator are up
      regulated during unilateral ureteral obstruction in adult rats.
AB  - PURPOSE: The plasminogen activator (PA)-plasmin system has been shown to
      influence turnover of the extracellular matrix in various tissues. We examined
      the alteration of plasminogen activator inhibitor-1 (PAI-1) and tissue-type
      plasminogen activator (t-PA) in kidneys with unilateral ureteral obstruction in
      rats. MATERIALS AND METHODS: Female rats that underwent ligation of the left
      ureter were sacrificed 12 hours, 1, 5 or 10 days later. The expressions of PAI-1
      and t-PA was determined by reverse transcription-polymerase chain reaction and
      immunohistochemical studies in the obstructed and contralateral kidneys in each
      group. RESULTS: Control kidneys showed no PAI-1 messenger (m)RNA expression.
      After days 1 through 10 of unilateral ureteral obstruction the amount of PAI-1
      mRNA significantly increased in obstructed compared with contralateral kidneys (p
      <0.01). Meanwhile, slight polymerase chain reaction products of t-PA were
      observed in control kidneys. After 12 hours through 10 days of unilateral
      ureteral obstruction, t-PA mRNA in obstructed and contralateral kidneys was
      significantly elevated compared with in control kidneys (p <0.05). No significant
      difference in t-PA was observed in the obstructed and contralateral kidneys in
      each group. Immunoreactivity to PAI-1 and t-PA was identified in obstructed
      kidneys. CONCLUSIONS: PAI-1 and t-PA are up-regulated in obstructed rat kidneys.
      Our results indicate that the PA-plasmin system has a role in the process of
      matrix accumulation and degradation during rat obstructive nephropathy.

PMID- 11832780
TI  - Modulation of bladder alpha1-adrenergic receptor subtype expression by bladder
      outlet obstruction.
AB  - PURPOSE: alpha1-Adrenergic receptor (alpha1AR) antagonists are effective for
      relieving obstructive and irritative symptoms in patients with bladder outlet
      obstruction. While the alpha1aAR is responsible for prostate smooth muscle
      relaxation and outlet obstruction relief, to our knowledge the mechanisms
      underlying the relief of irritative symptoms remain to be determined. Therefore,
      we investigated mechanisms by which bladder alpha1AR subtypes may be involved in
      this process. MATERIALS AND METHODS: We studied 42 rats, including 6 unoperated
      controls, 17 sham operated controls and 19 obstructed animals. Animals were
      characterized for baseline voiding pattern, followed by surgical intervention or
      sham surgery to establish obstruction (1.09 mm. restricted opening). After 6
      weeks to enable the development of detrusor hypertrophy, voiding behavior was
      reexamined, the animals were sacrificed and bladder tissue was immediately placed
      in liquid nitrogen. alpha1AR subtype messenger (m)RNA was quantitated using
      quantitative competitive reverse transcriptase-polymerase chain reaction and
      protein expression was determined using radioligand binding with the alpha1AR
      antagonist [125iodine]2-(-[4-hydroxyphenyl]-ethyl-aminomethyl)tetralone
      (saturation analysis for total alpha1AR density and competition analysis with
      BMY7378 and 5-methylurapidel to determine alpha1AR subtypes). RESULTS: In this
      model 6-week surgical obstruction produced a 6.3-fold increase in bladder weight
      versus sham operation (p <0.001), concurrent with increased voiding frequency
      versus before obstruction (p <0.004). Although bladder alpha1AR density did not
      increase overall with obstruction, striking changes in alpha1AR subtype
      expression occurred. In control animals 70% of alpha1AR mRNA was the alpha1a
      subtype, 5% were alpha1b and 25% were alpha1d, whereas in obstructed animals
      bladder alpha1AR expression changed to 23% alpha1a, 2% alpha1b and 75% alpha1d.
      Changes in alpha1AR mRNA expression were of similar magnitude throughout the
      bladder dome, mid body and base. Parallel changes were also evident at the
      protein level with 100% alpha1aAR expression in control animals changing to new
      onset alpha1dAR expression (mean plus or minus standard error of mean 36% +/- 7%)
      in animals with a 5-fold or greater increase in bladder weight. CONCLUSIONS: Our
      findings indicate a remarkable increase in bladder alpha1dAR mRNA and protein
      expression after 6 weeks of obstruction and resultant detrusor hypertrophy. This
      finding is potentially important since alpha1dARs have 10 to 100-fold higher
      affinity for the endogenous neurotransmitter norepinephrine than the alpha1a or
      alpha1bAR subtypes. These findings imply that targeting alpha1d may provide a new
      therapeutic approach for controlling bladder irritative symptoms and possibly
      detrusor overactivity associated with bladder outlet obstruction.

PMID- 11832781
TI  - Spinal implants of olfactory ensheathing cells promote axon regeneration and
      bladder activity after bilateral lumbosacral dorsal rhizotomy in the adult rat.
AB  - PURPOSE: We performed spinal implantation of olfactory ensheathing cells to
      demonstrate dorsal root afferent regeneration as well as bladder activity
      restoration after lumbosacral L6 to S2 rhizotomy. MATERIALS AND METHODS: Spinal
      segments receiving bladder innervation, usually L6, S1 and S2, were identified by
      bipolar stimulation of the ventral roots. Bilateral section of the identified
      dorsal roots L6 to S2 was performed in 18 male Wistar rats. Immediately after
      rhizotomy olfactory ensheathing cells or vehicle was unilaterally injected in the
      vicinity of the sacral parasympathetic nucleus in 9 rats each using a glass
      micropipette and air pulse system. The severed roots were reattached to the cord
      with fibrin glue and the animals recovered under antibiotic prophylaxis. RESULTS:
      Anatomical regeneration of bladder wall primary afferents was demonstrated by the
      presence of labeled wheat germ agglutinin-horseradish peroxidase fibers in the
      dorsal horn and sacral parasympathetic nucleus in 8 of 9 cases of olfactory
      ensheathing cell implantation but not in the 9 controls injected with vehicle.
      One week after surgery all rats had an atonic bladder on cystometrography. At 6
      weeks 8 of the 9 olfactory ensheathing cell implanted rats had recovered bladder
      activity. No recovery was observed in controls, in which vehicle was injected
      instead of olfactory ensheathing cells. CONCLUSIONS: Regenerated primary afferent
      fibers from the bladder project to the sacral parasympathetic nucleus, where they
      presumably form synapses mediating the recovery of bladder activity. Thus,
      olfactory ensheathing cell implants in the adult rat promote sensory axon
      regeneration, target reinnervation and bladder activity restoration.

PMID- 11832782
TI  - Rabbit muscle and urethral in situ biocompatibility properties of the self
      reinforced L-lactide-glycolic acid copolymer 80: 20 spiral stent.
AB  - PURPOSE: A new type of self-reinforced L-lactide-glycolic acid copolymer, molar
      ratio 80:20, stent was developed. We evaluated the tissue biocompatibility
      properties of the new material. MATERIALS AND METHODS: Rods made of self
      reinforced L-lactide-glycolic acid copolymer were inserted into rabbit dorsal
      muscles and rods of latex or polyvinylchloride and silicone served as positive
      and negative controls, respectively. Urethral stents of self-reinforced L-lactide
      glycolic acid copolymer and steel were inserted in situ via cystoscopy into the
      rabbit prostatic urethra. The animals were sacrificed after 2 weeks, 1, 2 and 3
      months, respectively. In situ histological analysis was done. Tissue reactions
      around the implantation types were analyzed histologically and scored
      semiquantitatively. In addition, macroscopic analysis was done of the urethral in
      situ stents. RESULTS: In rabbit muscle implantation test tissue reaction to the
      self-reinforced L-lactide-glycolic acid copolymer stent resembled that of
      negative control silicone. Less than moderate chronic inflammatory changes
      gradually subsided after 2 weeks. Foreign materials in the tissue and the
      reaction to these materials began to disappear after 1 month and at 3 months were
      completely absent. All rabbits fitted with the stent voided normally
      postoperatively. Self-reinforced L-lactide-glycolic acid copolymer stents were
      soft, partially fragmented and easily disintegrated when touched at 2 months, and
      were almost completely degraded at 3 months. The material did not encroach into
      the urethral wall macroscopically or microscopically. No calcification on the
      self-reinforced L-lactide-glycolic acid copolymer stents or bladder stone
      formation was seen. CONCLUSIONS: The new self-reinforced L-lactide-glycolic acid
      copolymer 80:20 material is safe, highly biocompatible and suited for future
      clinical use. It is most appropriate for preventing postoperative urinary
      retention after most minimally invasive thermal treatments for benign prostatic
      hyperplasia.

PMID- 11832783
TI  - Spermatogenesis, fertility and sexual behavior in a hypospadiac mouse model.
AB  - PURPOSE: Administering of flutamide to pregnant mice causes hypospadias in male
      offspring. We investigated spermatogenesis, fertility and sexual behavior in this
      hypospadiac mouse model. MATERIALS AND METHODS: Male offspring exposed to
      flutamide during the embryonic period were divided into hypospadiac group 1 and
      normal external genitalia group 2. Control group 3 consisted of male offspring
      not exposed to flutamide. We analyzed the spermatogenesis, epididymides sperm
      motility, in vitro fertilization rate and sexual behavior of each mouse. RESULTS:
      There were no significant differences in the weight of the testes or mean
      seminiferous tubular diameter in the groups. The number of apoptotic germ cells
      per unit area was not significantly different in the 3 groups. In groups 1 to 3
      there were no significant differences in the mean epididymides sperm motility
      rate plus or minus standard deviation (62.6% +/- 10.0%, 57.2% +/- 7.0% and 67.0
      +/- 7.6%) or in the in vitro fertilization rate (52%, 48% and 48%, respectively).
      However, there were significant differences in groups 1 to 3 in mean mounting
      frequency (0, 29 +/- 4.0 and 12.4 +/- 4.5 times per hour) and mean intromission
      frequency (0, 24.4 +/- 3.5 and 3.8 +/- 1.5 times per hour, respectively). Females
      coupled with group 1 or 2 male mice did not achieve pregnancy. CONCLUSIONS: These
      results suggest that spermatogenesis, sperm motility and fertilization in vitro
      were unaffected in hypospadiac mice but sexual motivation and arousal were
      deficient.

PMID- 11832784
TI  - Development of the conditionally immortalized testicular Sertoli cell line TTE3
      expressing Sertoli cell specific genes from mice transgenic for temperature
      sensitive simian virus 40 large T antigen gene.
AB  - PURPOSE: We developed and characterized a conditionally immortalized testicular
      Sertoli cell line from transgenic mice bearing the temperature sensitive simian
      virus 40 large T antigen gene pSVtsA58. MATERIALS AND METHODS: Established cells
      from 8-week-old male transgenic mice were cultured at a permissive (33C) or
      nonpermissive (39C) temperature on a collagen type I pre-coated culture vessel.
      The expression of Sertoli cell specific proteins was analyzed by reverse
      transcriptase-polymerase chain reaction, immunocytochemical testing and Western
      blot analysis. RESULTS: The Sertoli cell line TTE3 grew at 33C but not at 39C.
      Large T antigen was expressed only in the nuclei at 33C, indicating that the
      temperature sensitive growth phenotype of the cells arose as a result of the
      function of temperature sensitive simian virus 40 large T antigen. The cells did
      not show any colony forming activity in soft agar or form tumors in subcutaneous
      tissue in nude mice, showing that TTE3 cells were not transformed. The cells
      expressed messenger RNAs encoding steel factor, inhibin-alpha, transferrin,
      follicle-stimulating hormone receptor and sulfated glycoprotein-2. Moreover,
      expression of vimentin and zonula occludens-1 was observed in the cytoplasm and
      on the boundaries of the cells, respectively. Interestingly expression levels of
      transferrin and zonula occludens-1 were significantly elevated at 39C.
      CONCLUSIONS: TTE3 cells with these unique characteristics should serve as a
      useful model to study the regulation of Sertoli cell function.

PMID- 11832785
TI  - Quo vadis cesarean delivery?

PMID- 11832786
TI  - Effect of pregnancy on bone mineral density in healthy women.
AB  - Despite numerous studies and case reports of changes in bone mineral density
      (BMD) during pregnancy, the postpartum, and lactation, controversy exists
      regarding the time course of BMD changes and recovery to baseline levels. The
      degree to which pregnancy affects BMD long-term remains unclear. Several
      influencing factors, including breast-feeding, length of amenorrhea after
      pregnancy, and parity, have been studied with respect to changes in BMD in
      healthy women. We conducted the first systematic review of its kind on this topic
      and evaluated the 23 identified citations according to the U.S. Preventive
      Services Task Force rating scale. Six studies qualified as Level II-2, 12 were
      Level II-3, and 5 were Level III. There seems to be good evidence that calcium is
      mobilized from the maternal skeleton to that of the developing fetus during
      pregnancy. However, the eventual return of BMD to prepregnancy values suggests
      that maternal bone loss may not be permanent. Results from the studies that
      specifically evaluated the effect of lactation on BMD were varied, ranging from a
      decrease in BMD to no change. Of the studies that evaluated the effect of parity
      on BMD, none found an association linking a greater number of pregnancies to
      greater decreases in BMD. Pregnancy-associated osteoporosis seems to be uncommon,
      based on the limited published reports. Overall, no long-term adverse clinical
      effects have been noted in healthy women who had at least one ongoing pregnancy,
      despite the good evidence that some bone loss does occur soon after delivery.
      Additional longitudinal studies need to be undertaken to provide more definitive
      information on the effects of pregnancy on BMD and risk of osteoporosis later in
      life.

PMID- 11832787
TI  - Focus on primary care: from nevus to neoplasm: myths of melanoma in pregnancy.
AB  - Malignant melanoma is one of the few malignancies that regularly affect women
      during their childbearing years. Additionally, the incidence of melanoma has been
      increasing over the last several decades. Early diagnosis of stage I disease may
      lead to curative therapy; thus it is important for physicians and midwives to do
      a full examination of the skin. However, the myth that nevi may naturally grow or
      change during pregnancy has been shown not to be true and should not delay a
      diagnostic evaluation of a suspicious nevus. Older studies had theorized a worse
      outcome for pregnant women with melanoma. However, multiple controlled series and
      investigations have found that stage for stage this cancer is not affected
      adversely by pregnancy. Prognosis, recurrence, and incidence of melanoma seemed
      to be unaffected. Estrogen-containing oral contraceptives, as well as hormone
      replacement therapy, have no adverse affect on the disease.

PMID- 11832788
TI  - Noncontraceptive health benefits of intrauterine devices: a systematic review.
AB  - Most women and their clinicians are unaware that IUDs confer important
      noncontraceptive health benefits. This review summarizes the evidence from
      published articles on this topic. We conducted a series of systematic literature
      searches to identify articles on the noncontraceptive health benefits of IUD use.
      We reviewed the potentially pertinent ones for content, grouped them according to
      type of IUD, and evaluated them using the U.S. Preventive Services Task Force
      rating system. Over 500 titles were identified and several hundred abstracts were
      reviewed. Use of nonhormonal IUDs (plastic and copper) was associated with a
      decrease in endometrial cancer. The levonorgestrel intrauterine system can treat
      a variety of gynecological disorders, including menorrhagia and anemia. The
      levonorgestrel system has also been used successfully as part of hormone
      replacement therapy, as adjuvant therapy with tamoxifen, and as an alternative to
      hysterectomy for women with bleeding problems. Like oral contraceptives,
      intrauterine contraceptives confer important noncontraceptive health benefits.

PMID- 11832789
TI  - Welcome back, tax and spend?

PMID- 11832790
TI  - An evaluation of a clinical supervision programme.
AB  - In response to needs identified by community nurses in remote and isolated areas
      in North Argyll, Scotland, a programme of clinical supervision was implemented.
      The term 'practice support' was chosen by the community nurses for this project.
      The purpose was to provide peer support to counteract geographical isolation and
      to facilitate professional development through the use of reflective practice.
      Practice support was carried out over a period of 9 months. Pre-implementation
      and post-implementation questionnaires were used to evaluate the project.

PMID- 11832791
TI  - The prevalence of bacteriuria in older institutionalized patients.
AB  - We set out to determine the prevalence of bacteriuria in elderly patients
      institutionalised in 10 homes in Northumberland. Single mid-stream urine (MSU)
      specimens were collected from 161 asymptomatic patients aged 64-101 years. Thirty
      four (21%) samples had > 100 white blood cells (WBC/microliter) on microscopy as
      well as a significant bacteriuria of > 10(8) bacteria/l, being suggestive of a
      true urinary tract infection. A total of 115(71%) samples had < 100 WBC. Seventy
      five (46%) samples could be described as 'contaminated' or 'infection unlikely'
      but of these only 31 (19.2% of all samples) were reported as 'contaminated' by
      the laboratory. This study confirms previous work in America to indicate the high
      level of bacteriuria in institutionalised elderly patients as well as the very
      high number (46%) who may show bacteriuria but no rise in the number of WBC
      suggesting contamination only. Nurses and GPs must be very cautious in
      interpreting MSU results from such patients.

PMID- 11832792
TI  - Bereavement visiting: older people's and nurses' experiences.
AB  - A review of the relevant literature failed to find material specifically related
      to the older person's experience of bereavement visiting by community nurses.
      Since the community nurse's role includes actively visiting older people who have
      been bereaved it was considered worthwhile to explore the service from the
      perspectives of both older bereaved people and community nurses. The study has
      addressed a number of issues in the wider literature and highlighted certain
      models of care which this literature advocates. This ongoing study uses
      qualitative and survey approaches; a sample of 20 community nurses and 10 older
      people were interviewed and the interviews were then analysed in order to
      identify core concepts. The core concepts from older people were found to be
      relationships and their perceptions of self. The core concepts from the viewpoint
      of community nurses were relationships, practice and organizational aspects of
      care.

PMID- 11832793
TI  - Needs of older people in the community: issues for PCGs and PCTs.
AB  - National policy (Department of Health, 1997, 2000) is directing care provision to
      being appropriate to meet people's needs; to be effective; evidence-based;
      efficient and economic. Primary care groups (PCGs) and trusts (PCTs) have been
      identified as being the organizations to deliver such care. Since the
      introduction of the NHS and Community Care Act 1990, certain issues have been
      highlighted as having implications for the provision of an 'ideal' service for
      older people on the community. These issues focus around three main areas:
      assessment of need; working in partnership and quality of service provision. This
      article discusses these issues and their implications for PCGs/PCTs in relation
      to supporting older people in the community.

PMID- 11832794
TI  - Caring for dry and damaged skin in the community.
AB  - Community nurses are ideally place to fully utilize nurse prescribing to improve
      the accessibility to emollient therapy for any patient with dry skin, regardless
      of cause. Skin diseases affect 23% of the general population and patients
      accessing care in the primary setting contribute to 15-20% of general practice
      appointments.

PMID- 11832796
TI  - Total continuity of care may not be achievable.

PMID- 11832795
TI  - Critique of a protocol for annual review of older people with diabetes.
AB  - In this article we present a critical evaluation of the development of a protocol
      to support district nurses in the domiciliary annual review of older people with
      diabetes. We discuss the protocol's development, identifying its limitations and
      making recommendations for its use. We conclude that although the protocol is a
      useful starting point its validity is challenged by a lack of primary research
      regarding the care of older people with diabetes. More work is needed to identify
      appropriate remedial therapy following the annual review. The health education
      component also requires development to better reflect the different needs of
      older people.

PMID- 11832797
TI  - Free nursing care for all - a half-hearted gesture.

PMID- 11832798
TI  - Enteral tube feeding training for nurses and care assistants.
AB  - Increasing numbers of patients are enteral tube-fed in the community, often
      requiring community nursing support. Appropriate training facilitates effective
      patient care in this rapidly changing area of practice. The project described
      involved the development, piloting and evaluation of a validated home enteral
      tube-feeding training programme for community staff. Following wide consultation,
      four pilot days were provided (two for registered nurses and two for care
      assistants) which were positively evaluated. Post-training evaluation suggested
      the training led to beneficial changes in practice. Additional funding obtained
      has enabled the basic training to continue on a monthly basis for 2 years with
      biannual updates. Significant risks are attached to home enteral tube feeding;
      opportunities to integrate theory and practice in a safe environment should
      enhance patient care and decrease clinical risk.

PMID- 11832799
TI  - Developments in education and training for nursing home staff.
AB  - The independent sector has always provided a proportion of the care needed for a
      variety of client groups in the UK. Although the vast majority of the recipients
      of care are older people, groups such as those with mental health problems and
      those suffering from various disabilities are also cared for. The sector is
      currently facing the need for major changes in the way it provides care.
      Legislation and a number of reports and strategy documents mean that these
      changes are necessary for the sector to survive. To drive and to respond to the
      new situation, education and training has a part to play. This article will
      examine how the new situation following the sector will impact on the education
      needs for nurses.

PMID- 11832800
TI  - Eroding the barriers between public and private health care.

PMID- 11832801
TI  - Recent developments in the management of type 2 diabetes.
AB  - Type 2 diabetes is a common, chronic disease, with a high risk of macrovascular
      and microvascular complications that lead to premature death and disability. The
      disease is managed largely in primary care and its rising prevalence will
      increase the workload of community nurses. The forthcoming Diabetes National
      Service Framework will aim to improve the standards of diabetic care, while
      scientific and technological developments offer new treatments that may also
      improve the outlook for patients. There is as yet no case for population
      screening for type 2 diabetes, but community nurses are ideally placed to carry
      out local screening initiatives based on consensus guidelines.

PMID- 11832802
TI  - Culturally sensitive care: managing diabetes during Ramadan.
AB  - Diabetes and its treatments can cause problems for Muslims who wish to take part
      in the fast during the holy month of Ramadan. This article offers information
      about the impact of various diabetes treatments, including insulin, when fasting
      and some of the precautions that need to be in place. Some of the reasons people
      with diabetes might find it difficult to comply with advice are explored with
      some suggestions on how to work towards acceptable compromises. Through dialogue
      between health professionals and patients, it is usually possible to facilitate
      at least some safe fasting for those who wish to observe this annual ritual.

PMID- 11832803
TI  - Informal peer support: a key to success for nurse prescribers.
AB  - A study was conducted in Leicestershire and Rutland (NHS) Healthcare Trust to
      determine the continuing professional development needs of nurse prescribers.
      Qualitative and quantitative approaches were applied to the sample frame of 350
      nurse prescribers to elicit the most significant factors which have influenced
      the development of nurse prescribing. The majority of nurse prescribers
      considered prescribing to be a skill, which is now an essential part of core
      practice. The study indicated that informal peer support seems to have
      compensated for the absence of formal clinical supervision. Any development such
      as nurse prescribing has the added benefit of examining practice from new
      perspectives. Reflection on how this was achieved highlights important issues as
      to how the next stage can be even more successful.

PMID- 11832804
TI  - Developing a framework for primary palliative care services.
AB  - Practice and empirical data indicate concerns regarding the delivery of primary
      palliative care, particularly the provision of a multidisciplinary approach. A
      collaborative study was undertaken between an academic unit and primary care
      practice to evaluate current care provision and explore methods of developing
      services. A two-phase study was carried out over a period of 18 months using an
      action research approach, in order to facilitate concurrent service evaluation,
      change in practice, and the involvement of professionals in research and practice
      development. The first phase highlighted the need to enhance primary palliative
      care services; a number of practice changes were identified and implemented
      during the second phase and evaluated using quantitative and qualitative methods.
      Data demonstrated the enhancement of services, benefits to patient care and
      professional working and the viability of an innovative model of palliative care
      delivery - that of a surgery-based clinic for palliative care patients and
      carers. A framework for the provision of multidisciplinary palliative care in the
      community was developed.

PMID- 11832805
TI  - Uncommon disorders: meeting patients' needs.

PMID- 11832806
TI  - Community nursing research on the up.

PMID- 11832807
TI  - Promoting patient partnership in wound care.
AB  - Involving patients in their care is a key component of the NHS plan and clinical
      governance (Department of Health, 1999a). Involvement is enhanced through nurse
      patient relationships which are based on partnership in which the patient's
      viewpoint is given equal weight to that of the practitioner. In the management of
      wounds, this may be complex due to conflict between clinically effective
      treatment and a patient's wish. High quality care relies on a holistic assessment
      of the patient and a negotiated care plan which is implemented and evaluated in
      order to judge the effectiveness of care.

PMID- 11832809
TI  - An audit of problems associated with urinary catheter withdrawal.
AB  - Long-term catheterisation is associated with many complications, including
      urinary tract infections which may lead to encrustation and catheter blockage.
      Current management of catheters susceptible to frequent blocking is to attempt to
      prolong catheter life by using bladder maintenance solutions or to change
      catheters proactively by identifying a characteristic blocking pattern for the
      patient. However, catheter removal is associated with a number of problems. This
      article describes an audit conducted in one trust to identify the types of
      catheter material associated with removal difficulties. All-silicone catheters
      appeared to have a higher incidence of reported problems. The formation of a
      'cuff' in all-silicone catheters when the catheter balloon fails to deflate to
      its original shape has been investigated as an important factor in difficult
      removal. The audit also examined what action was taken when nurses were unable to
      remove a catheter.

PMID- 11832808
TI  - Barriers to research implementation by community nurses.
AB  - This article presents the community findings from a study of nurses in community
      and acute settings using Funk et al's Barriers to Research Utilization Scale
      (Barriers) (Funk et al, 1991a), which aimed to identify the main barriers to
      implementing research in practice. The Barriers questionnaire was sent to all
      nurses working in three community trusts in Yorkshire (n=2327), and practice
      nurses in one Yorkshire health authority (n=190). A 51.5% response rate gave a
      sample of 1297 nurses. The top two barriers were reported to be lack of time and
      resources. There were significant differences between sub-samples, e.g. older
      women perceived more barriers than younger colleagues, and practice nurses had
      particular problems with the cooperation of GPs. Factor analysis generated four
      new factors different from those found by Funk et al (1991a) (shown in brackets):
      benefits (nurse characteristics); quality (research characteristics);
      accessibility (presentation of the research characteristics) and resources
      (setting characteristics). Recommendations include developing nurses' critical
      appraisal skills so that, given more time and adequate resources, research
      findings might be judiciously implemented in practice.

PMID- 11832810
TI  - Continence assessment in primary care: what is the next step?
AB  - There are many assessment 'forms' available for the collection of information in
      relation to bladder dysfunction. In many cases such forms have not been fully
      validated and should only be considered on a face validity basis. Validated
      symptom scores are available but these are generally used within specific areas
      of urology, e.g. lower urinary tract symptom scores for prostate screening. This
      article explores the need for an improved validated assessment and symptom
      scoring tool for nurses within primary care, to enable nurses to establish a
      preliminary diagnosis in adult patients presenting with bladder symptoms.

PMID- 11832811
TI  - Community nurses' contribution to oral health.
AB  - Oral health is an important component of general health and well-being. Although
      oral health has improved dramatically in children and young adults, oral diseases
      remain common, particularly among disadvantaged and vulnerable groups. Many
      patients seen by community nurses will fall into these categories and are less
      likely to have sought treatment. This article presents the epidemiology of oral
      diseases and conditions for specific groups in society that community nurses will
      be caring for. It looks at prescribing principles and describes treatment and
      advice for common oral conditions, including those where prescription may be
      appropriate. Community nurses play an important role in the oral health care of
      society, particularly among those least likely to access dental services.

PMID- 11832812
TI  - Diagnosis and treatment of osteoporosis.
AB  - Osteoporosis is a serious, debilitating and potentially fatal chronic disease
      which places a major burden on both the patient and the NHS. In order to tackle
      this growing problem successfully, it is essential that it is diagnosed in its
      early stages so that fractures can be prevented. Nurses in particular can make a
      big difference, as they are ideally placed to proactively identify those who may
      be at risk from osteoporosis. This article explains the essential role the nurse
      can play, highlights the risk factors and symptoms nurses should be looking out
      for, and provides a brief summary of all the management options available, so
      that nurses can make informed recommendation on the most appropriate treatment.

PMID- 11832813
TI  - Can everyone's expectations be met?

PMID- 11832814
TI  - Sexual health is no laughing matter.

PMID- 11832815
TI  - Hypodermoclysis for rehydration in the community.
AB  - During 1999 and 2000 the practice development unit of Greater Glasgow Primary
      Care Trust received an increasing number of requests from community staff for
      guidance in caring for patients receiving subcutaneous fluids for rehydration.
      This article describes the process of developing guidelines in order to address
      the issue. Hypodermoclysis is a relatively safe, simple and cost-effective
      technique, suitable for use in the community with a range of client groups, e.g.
      older people or those recovering from recent cardiovascular accidents. Its use in
      palliative care, however, raises problems in terms of clinical evidence and
      ethical issues which need to be addressed. Various factors, i.e. products not
      being licensed for this specific use, staff requests for clinical guidance and
      the anticipated increasing use of hypodermoclysis for rehydration, all indicated
      the need for a collaborative approach, address the complexity of issues in the
      decision-making process and provide clinical guidance with the aim of improving
      nursing practice and patient outcomes.

PMID- 11832816
TI  - The attitudes of GPs towards the nurse-practitioner role.
AB  - In recent years, nursing and health-care policy have promoted the advanced role
      of the nurse -- that of nurse practitioner. But such a role has not been
      integrated widely into the primary health-care team. This study investigates the
      knowledge and attitudes of GPs who do not employ nurse practitioners to find out
      what prevents them doing so. Ten GPs who did not already employ a nurse
      practitioner took part in semi-structured interviews. Our findings show that GPs,
      although confused about the role, were generally supportive of advanced nursing
      practice. Skills identified with the role were prescribing, disease diagnosis and
      minor-illness management. GPs thought that protocols and guidelines should govern
      practice, which differs fundamentally from the Royal College of Nursing
      definition. None of the GPs had encountered the role in primary care, and the
      lack of professional regulation and role definition for practice nurses and nurse
      practitioners who work in primary care may have affected GPs' perceptions.

PMID- 11832817
TI  - The role, responsibilities and educational needs of the non-nurse carer.
AB  - Non-nurse carers have been a feature of the British health-care system for many
      years. Changes in the health service, including the loss of nurses from the
      workforce, have led to the increased use of non-nurse carers being advocated.
      However, if they are to be employed effectively, issues relating to their role,
      responsibilities and educational needs must be carefully addressed. This article
      examines literature on the contribution of non-nurse carers to the nursing
      profession in acute and primary care settings and the attitudes of qualified
      nursing staff, and highlights attempts to define the role and its requirements.

PMID- 11832818
TI  - Use of gloves in the community: why, when, which and how?
AB  - The use of gloves has become routine since the early 1980s. It is recognized that
      they have an important part to play in the protection of both staff and
      patient/clients in the prevention of cross-infection. However, as choices
      relating to glove usage have increased over the years, health-care staff need to
      adopt a risk assessment approach, considering why, when, which and how gloves
      should be used. This article outlines the different types of gloves available and
      when they should be used.

PMID- 11832819
TI  - Celebrating the present, challenging the future of nurse prescribing.
AB  - As universities gear up to deliver the next wave of nurse prescriber training,
      this article -- based in part on the experiences of the University of Derby and
      its partner trusts and the recent consultation document (Department of Health,
      2001) -- considers the issues underpinning the education and training of nurse
      prescribers. The collaborative, cooperative and coordinated approach seen in the
      training of the first wave facilitated the preparation of large numbers of
      practitioners to prescribe while maintaining service provision to patients in the
      community. The success of the programme should be celebrated, but also raises
      topics for debate as nurse prescribing expands to include a much wider range of
      nurses. The consultation document identifies the range of medicine from which it
      is proposed nurses will be able to prescribe and outlines the education and
      training parameters that will underpin the new prescribing requirements. It is
      clear that some challenges similar to those experienced during the first wave of
      nurse prescribing will arise, but there are also some significant differences
      that have raised pertinent questions and require answers.

PMID- 11832820
TI  - District nurse-led beds: an alternative to care at home.
AB  - Intermediate care is a key feature of the Government's plans for the development
      of the health service. The intermediate care scheme described here offers a
      district nurse-led bed (DNLB) stay in a community hospital to patients in the
      community who require short-term nursing help. District nurses are given the
      opportunity to admit patients from their community caseloads into a DNLB in a
      community hospital and are responsible for their admission, care and discharge.
      This article describes the pilot study that monitored the first 30 patients who
      used the DNLBs. Patients included younger people with multiple sclerosis who were
      admitted for respite care, but the principal beneficiaries were those aged over
      65 years with chronic conditions.

PMID- 11832821
TI  - Wound care assessment with the Polaroid Macro 3 SLR.

PMID- 11832822
TI  - Nurse prescribing gathers momentum.

PMID- 11832824
TI  - The answer to reducing patient violence towards NHS staff.

PMID- 11832823
TI  - Was the House of Lords right to dismiss Mrs Pretty's appeal?

PMID- 11832825
TI  - Nurse who disclosed to the press details about a celebrity patient.

PMID- 11832826
TI  - Acceptability of early discharge with drain in situ after breast surgery.
AB  - The aim of this study was to evaluate a policy of early discharge at 48 hours
      with suction drains in situ in a cohort of patients undergoing surgery for breast
      cancer and to compare this with a similar cohort of patients discharged 5 days
      postoperatively. This was an integrated qualitative/quantitative study using a
      questionnaire given to both groups providing comparable results by using averages
      and percentages to describe and synthesize the data. A questionnaire of open and
      closed questions was given to 19 patients who chose to be discharged at 48 hours
      with drains in situ, and 16 patients who opted to be discharged at 5 days after
      drain removal. The study demonstrated that patients regarded early discharge as
      being safe and were satisfied with their care when they were given a high level
      of support from hospital and community staff. The results also identified that it
      was important for patients to make their own decision about either early
      discharge or standard discharge in order to be satisfied with the outcome of
      their care.

PMID- 11832827
TI  - Urinary tract stones: cause, complications and treatment.
AB  - Stones or calculi in the urinary tract affect up to 12% of men and 5% of women by
      the age of 70 years, with more than a third of individuals having a strong family
      history (Unwin, 1996). Complications include obstruction in the urinary tract,
      pain, nausea, vomiting and sepsis. Common causes are: urine stasis, infection,
      presence of foreign bodies, dehydration, diet and periods of immobility.
      Encouraging initial diuresis could exacerbate rather than relieve symptoms.
      Discharge advice is a key feature of preventing recurrence once the predisposing
      factors have been identified. The relationship between patient and nurse is an
      invaluable and ideal opportunity for nurses to educate patients in appropriately
      changing dietary habit and in maintaining a urine output of greater than 2 litres
      per day.

PMID- 11832828
TI  - Emergency nurse practitioners: should the role be developed?
AB  - Trusts have to face a number of challenges in the provision of accident and
      emergency (A&E) services. One suggested way forward is to introduce the emergency
      nurse practitioner (ENP) role into A&E. However, this is not without controversy.
      Thus, this review has been undertaken in order to identify and assess any
      available evidence. A total of nine studies met the inclusion criteria. The
      studies fell into a number of categories, e.g. overall evaluation of the role,
      the use of radiography, and patient satisfaction. Several studies monitored
      transit times though A&E and there was some limited cost-benefit analysis.
      Overall, there was little difference found between the performances of ENPs in
      comparison with that of senior house officers (SHOs). The studies available for
      review are of poor quality, which limits the conclusions that can be made. At
      best, it would be reasonable to state that there is no evidence to demonstrate
      that ENPs are better or worse than SHOs in seeing, treating and discharging
      patients with minor injuries in A&E.

PMID- 11832829
TI  - Introducing a professional doctorate in nursing and midwifery.
AB  - The convergence of a number of factors has led to the emergence of what has come
      to be known as the 'professional doctorate'. This new doctoral education diverges
      from the model of research doctorates that have historically predominated for
      more than a century. The background to these changes and the impetus for the
      development of this relatively new approach to doctoral preparation is outlined
      in this article. The infancy of the professional doctorate means little empirical
      data exist about their operation or their success. In this light, the development
      of an evaluative framework is described in relation to the implementation of a
      new professional doctorate for nurses and midwives that has been introduced at
      the University of Sheffield.

PMID- 11832830
TI  - Legal aspects of consent 18: issues relating to euthanasia.
AB  - Case Scenario: Norah was in the terminal stages of cancer. She lived with her
      single daughter, Jane, and was being cared for by Macmillan nurses who came to
      see her daily. She was on a high level of morphine but still suffered
      considerable pain. A consultant in palliative care visited her to reassess her
      medication levels, but Norah found that the new medication still left her with
      considerable discomfort and pain. Norah asked her daughter to help her end her
      life. What is the law?

PMID- 11832831
TI  - Reflection: possible strategies to improve its use by qualified staff.
AB  - Reflection is now a prerequisite for all nurses, midwives and health visitors
      (UKCC, 2001). It is the method endorsed by the UKCC to promote the development of
      informed, knowledgeable and safe practice, and qualified practitioners are
      required to maintain a personal professional profile containing evidence of
      reflection on practice. The aim of this article is to examine why qualified
      practitioners may be reluctant to reflect formally, to speculate on the possible
      barriers to refection, and to suggest how reflection can be promoted positively
      as an integral part of nursing practice. The article begins with an examination
      of definitions of reflection, reflective theory and the purpose of reflection,
      and continues by questioning whether the concept of reflection has been embraced
      as eagerly by nurses at 'grass roots' as it has by academia, the nursing press
      and the UKCC. It is suggested that several barriers to effective reflection may
      create a division between practitioners and the professional hierarchy regarding
      the conceived common practice of reflection, and strategies are proposed that may
      help to overcome these barriers. The discussion concludes by prioritizing the
      need for a clear definition and concept analysis of reflection, supported by long
      term investment into research that explores the effect of reflection on clinical
      practice and patient care.

PMID- 11832832
TI  - Oasis?: an innovative alternative dressing for chronic wounds.
AB  - Chronic wounds in patients with multiple systemic factors present a significant
      clinical challenge for clinicians. Oasis? Wound Dressing is derived from porcine
      small intestine which, when placed in a non-infected wound, stimulates new tissue
      and an absorbable, natural template for the growth of new tissue. Emerging
      evidence suggests that it is beneficial for patients with chronic, non-healing
      wounds complicated by multiple systemic factors.

PMID- 11832833
TI  - Elderly patients must not be victims of shortages.

PMID- 11832834
TI  - Personal care: basic, simple and dispensable?

PMID- 11832835
TI  - Case 58: abuse of elderly patients. Staff nurse who assaulted and restrained
      elderly patients.

PMID- 11832836
TI  - Importance of pH monitoring in the care of long-term catheters.
AB  - One of the main complications encountered by patients with long-term in-dwelling
      catheters is that of catheter blockage as a result of encrustation. This is
      usually managed at a district nurse level by the administration of catheter
      maintenance solutions (CMSs) or frequent catheter changes. However, catheter
      changes and maintenance solutions are often only employed after blockage has
      occurred. Regular recording of catheter care and urinary pH monitoring can be
      utilized to optimize the management of long-term catheters and plan catheter
      changes and CMS administration in a prophylactic manner. This article reviews the
      literature regarding CMS and urinary pH and demonstrates how the introduction of
      continued and formalized recording of catheter care and pH monitoring can improve
      long-term catheter management.

PMID- 11832837
TI  - The concept of total pain: a focused patient care study.
AB  - This article considers the care of a patient admitted into a hospice environment
      for pain management and respite care. The concept of 'total' pain is discussed
      together with the need for a multidimensional assessment of pain to enable
      effective management to be accomplished. A multiprofessional approach to care
      along with inclusion of both the patient and her husband in decision making
      achieved the best possible quality of life for them both. A palliative care
      approach requires healthcare professionals to focus on the achievement of quality
      of life for all patients whose disease is not responsive to curative treatment.
      This is achieved by providing relief from pain and other distressing symptoms,
      including psychological, spiritual and social aspects of care, together with the
      acknowledgement of patient and relative autonomy. Hence, the study also
      exemplifies contemporary palliative care in action.

PMID- 11832838
TI  - Legal aspects of consent 15: living wills and the common law.
AB  - Case Scenario: Since watching a programme on dementia on the television, Sam had
      always been terrified of losing his mental faculties. He therefore told his
      daughter that if he ever suffered from a disease which lead to mental incapacity
      he would not wish to have any treatment. Some years later early signs of motor
      neurone's disease appeared and his condition worsened rapidly. He became
      incapable of swallowing and his mind deteriorated, so he was no longer able to
      express his views. His daughter told the healthcare staff at the hospital about
      his previous wishes and said that he would not wish to be fed artificially. Would
      staff be justified in giving him artificial feeding, contrary to the daughter's
      views?

PMID- 11832839
TI  - The nurse's role in assessing alcohol use by older people.
AB  - Nurses have the potential to carry out health promotion activity related to
      alcohol use in a range of settings where older people receive care. The majority
      of the literature on alcohol use in later life has focused on abuse, especially
      on the more common risk of drug-alcohol interactions. In order to work
      effectively with older people in health prevention and education, nurses need to
      be knowledgeable about older people's patterns of drinking, the effects of
      alcohol on medication and the current evidence on the harm and benefits of
      alcohol to health. In carrying out assessments, a skillful approach needs to be
      adopted in questioning older clients on what some might regard as a sensitive
      issue. Screening tools for the detection of alcohol abuse in the general adult
      population may not be valid for use with older clients. Tools specific to the
      detection of alcohol abuse by older people will be considered.

PMID- 11832840
TI  - Health needs assessment in intermediate care of elderly people.
AB  - The National Service Framework for older people (Department of Health (DOH),
      2001a) identifies health promotion as one of the eight standards for improving
      the health and well-being of older people. Population health needs assessment is
      the first stage in any public health promotion cycle. This article critiques
      health needs assessment methodology, investigates the origins of health needs
      assessment and discusses the application of health needs assessment theory in a
      community hospital setting.

PMID- 11832841
TI  - Continuing care after discharge from hospital for stoma patients.
AB  - The purpose of this study was to monitor the progress of patients given a
      permanent colostomy for colorectal carcinoma and to evaluate the need for nursing
      interventions or referral. A pretested semistructured interview schedule was
      used. Interviews were conducted at 1 week, 1 month, 6 months and 1 year after
      discharge. Complete data sets were obtained from 112 patients. In this study it
      was found that survival was strongly related to Dukes' staging system. More than
      half of those surviving to 1 year suffered fatigue, one in 10 had severe pain and
      one in five had parastomal hernia. At each interview approximately one in four
      people required intervention and one in 10 were referred. This study demonstrates
      the need for home visits and sustained patient contact. High priority should be
      given to a full benefit analysis of screening programmes, including the
      considerable costs of aftercare.

PMID- 11832842
TI  - Phantom bladder sensations: a new concern for stoma care workers.
AB  - The phenomena of phantom limb pain and sensations are well recognized in the
      medical literature. However, historically, there has been little more than
      passing reference to phantom pain and sensations of visceral organs. In
      particular, phantom bladder pain has been barely recognized. This article
      describes the result of a small survey of urostomists (n=50) who experienced
      bladder pain and sensations that were described by the respondents as being a
      perpetuation of the pain and sensations that they experienced before cystectomy
      or urinary bladder diversion surgery. Respondents reported a varied frequency of
      sensations, unhelpful healthcare professional responses and a range of strategies
      that they employed to deal successfully with the pain and sensations. The
      findings of this study are important because they have identified significant
      issues for stoma care patients that need to be addressed by those involved in
      stoma care and which could lead to significant quality of life improvements. This
      research has shown that stoma care workers need to include the possibility of the
      occurrence of phantom bladder sensations in preoperative counselling, acknowledge
      and support postoperative patients by confirming the validity of their experience
      and by using interventions, identified in this study, that can minimize the
      effects.

PMID- 11832844
TI  - Repress or reveal: a patient's choice.

PMID- 11832843
TI  - The use of wound drainage bags for complex wounds.
AB  - The routine use of drainage devices for wound management is relatively uncommon
      because of the extensive range of dressings available. However, there is an
      almost equally large range of wound drainage devices with different designs and
      properties from which to choose. Large, complex wounds with a fistula draining
      small bowel content are difficult to manage. This article focuses on wound
      drainage bags and explores the case of a patient with a large abdominal wound
      with a fistula at the lower end whose effluent was contained by Wound Manager
      (manufactured by Craig Medical, obtained from ConvaTec).

PMID- 11832845
TI  - Oral care for people with advanced cancer: an evidence-based protocol.
AB  - Poor oral health is an extremely common problem in patients with advanced cancer
      and, because of its impact on quality of life, promoting oral care should be
      regarded as a priority by every hospice and palliative care team. At Accord
      Hospice, Paisley, UK, a protocol for oral care has been developed which is
      simple, inexpensive and evidence-based. Evaluation of the protocol has shown that
      it can lead to significant and consistent improvements in oral health and
      comfort. A survey of mouth-care practices in other Scottish hospice units reveals
      that although much agreement exists, certain practices that are unsupported by
      research evidence are still undertaken.

PMID- 11832846
TI  - Randomized controlled trials in palliative care: overcoming the obstacles.
AB  - Problems associated with conducting randomized controlled trials (RCTs) in
      palliative care are well documented. Palliative care researchers commonly report
      difficulties with recruitment, attrition, and randomization. Despite these
      difficulties, there is a crucial need to enhance the evidence base of palliative
      care and RCTs are a recognized method for achieving this. Few publications to
      date have provided clear strategies for researchers considering RCTs in
      palliative care. This article presents an overview of the features of the RCT and
      reasons for using this research method. Problems with conducting RCTs are
      considered with discussion focusing on an approach for managing these hurdles.
      Examples are provided from an ongoing RCT investigating a support and information
      programme for lay caregivers of people receiving palliative care at home. The aim
      of the article is to provide a guide to conducting RCTs and to promote their use
      in palliative care when researchers are evaluating new interventions.

PMID- 11832847
TI  - Intensive care nurses' experiences of caring for dying patients: a
      phenomenological study.
AB  - The experience of nurses working in end-of-life care, particularly those caring
      for cancer patients in the hospice setting, have been well researched. Yet
      despite the fact that intensive care units (ICUs) are frequently the site of
      patient death, studies of the nurses working in these units are uncommon. This
      study was designed to provide qualitative data to explore the experiences of
      intensive care nurses caring for patients who are dying. Semi-structured
      interviews were conducted with ten nurses who had experience of caring for dying
      patients in ICUs in two teaching hospitals in Taiwan. Data were analysed using a
      phenomenological descriptive approach. Participants' descriptions revealed the
      following core themes: considering nurses' attitudes to caring for the dying,
      stressors associated with this care and coping strategies that intensive care
      nurses adopt. The study concludes that education for ICU nurses must address
      these issues to facilitate better care of dying patients in the ICU.

PMID- 11832848
TI  - The way forward: identifying palliative nursing research priorities within a
      hospice.
AB  - This article presents how practice issues within a hospice were identified as a
      means of prioritizing areas for research and development. The Delphi technique
      was employed to facilitate nurses working in the hospice to participate in the
      study. Forty-six practice issues were identified by the nurses and prioritized as
      areas of research in the hospice. This enabled comparisons with other studies and
      the literature to be made. The identified research priorities were then utilized
      to structure a framework for practice development in the hospice which included
      the use of weekly nurse meetings, interest groups and nurses studying for degrees
      and diplomas in order to address systematically the practice issues and develop
      an evidence-based practice approach.

PMID- 11832849
TI  - Relatives' views of health care in the last year of life.
AB  - This article reports the views of 155 relatives of patients who died during a 12
      month period with varying degrees of palliative care service (hospital-based,
      home care and no palliative care). Although overall care was rated as excellent
      or good by the majority of interviewees, the Critical Incident Technique
      (Flanagan, 1954) was used to gather examples of good and poor care from
      relatives' perspectives. These incidents are recounted here under a framework
      describing the process of care from access to services through to care at the
      time of death and aftercare for relatives. The range of incidents reported
      suggest that relatives consider all aspects of care - technical and interpersonal
      - as important towards the end of life, but particular importance is placed on
      the attitudinal and dignity-preserving aspects of care. The movement to integrate
      principles of palliative care into all clinical practice is reinforced by the
      findings from this study.

PMID- 11832850
TI  - [Laparoscopic surgery for colon diverticulitis].
AB  - BACKGROUND: Laparoscopic surgery is used with increasing frequency to treat
      colorectal pathologies and some groups have also attempted to treat the
      complicated forms of diverticulitis (abscesses and/or fistulas). The results
      reported in the international literature are still controversial, especially in
      terms of the duration of surgery, the frequency of laparotomic conversions and
      postoperative morbidity. The aim of this study was to analyse the results of
      laparoscopic or laparotomic treatment of diverticular disease of the colon in
      patients admitted to the Department of Colorectal Surgery at the Cleveland Clinic
      in Florida over a three-year period. METHODS: A retrospective analysis was made
      of 57 patients with diverticular disease of the colon who were admitted to CCF
      (Cleveland Clinic Florida) between January 1996 and December 1998 and underwent
      elective laparoscopic or laparotomic surgery. A comparative analysis was made of
      the results in the two groups. RESULTS: Of the 57 patients treated only 15
      underwent laparoscopic surgery; the majority were treated for uncomplicated
      diverticulitis. 22 out of 42 patients (53%) undergoing laparotomic surgery
      presented complicated diverticulitis (abscesses, fistulas or stenosis), whereas
      12 out of 15 patients undergoing laparoscopic surgery (80%) were treated for
      uncomplicated diverticulitis. Statistically significant differences were found in
      relation to the duration of surgery: 152 min in the laparotomic group vs 209 in
      the laparoscopic group. No differences were found in the frequency of
      intraoperative complications, transfusions and the number of drainages inserted
      (p=0.66). The postoperative period showed significant differences in terms of the
      reappearance of intestinal peristalsis, use of PCA and postoperative stay.
      CONCLUSIONS: This retrospective study confirms that the laparoscopic treatment of
      colon diverticulitis offers a number of advantages: reduced postoperative pain,
      more rapid recovery of intestinal peristalsis and shorter postoperative stay.
      Laparoscopic sigma colectomy represents the treatment of choice for
      diverticulitis in uncomplicated cases.

PMID- 11832851
TI  - Comparison between modern mesh and conventional non-mesh methods of inguinal
      hernia repair.
AB  - BACKGROUND: The objectives of the study were to compare the tension-free mesh
      repair with non-meash conventional repair of groin hernia. METHODS: In the past
      two years in 299 consecutive unselected patients 339 inguinal hernia repairs were
      carried out. They randomly allocated to undergo either a non-meash modified
      Bassini's repair (n=164) or a tension-free mesh repair (n=175). The latter group
      consisted of laparoscopic TAPP repair (n=46) and open onlay patch repair (n=64)
      or plug and patch repair (n=65). Operation time, postoperative pain and
      complications, hospital stay, return to work and recurrence were assessed.
      Statistical analysis was made using the "t"-Student test. RESULTS: The
      characteristics of the patients in each group and the operation time did not
      differ significantly. The planned procedure was completed in all and no death
      occurred. The analgesic requirements (none 2.5 vs 56.4%, opiods 77 vs 23.6%),
      complication rate (9.4 vs 4.3%), hospital stay (4.2 vs 1.8 days), return to work
      (17.2 vs 7.3 days) and recurrence rate (5.5 vs 1.2%) in non-mesh group were more
      than in the mesh group. All differences were statistically significant (p<0.05).
      Among the three subgroups of mesh group no statistically significant differences
      (p>0.05) were found. CONCLUSIONS: The tension-free mesh repair either open or
      laparoscopic provides excellent results with better short-term outcome and lower
      recurrence rate than non-mesh modified Bassini's repair.

PMID- 11832852
TI  - [Plug-technique for umbilical hernia repair in the adult].
AB  - BACKGROUND: Umbilical hernia represents 6% of all abdominal wall hernias in the
      adult. Surgical repair should always be carried out due to possible occurrence of
      complications. Aim of this paper is to evaluate the efficacy of the plug
      technique. METHODS: From October 1995 to April 2000, the authors performed 21
      operations for acquired umbilical hernia with a defect smaller than 4 cm. Local
      anesthesia was used and a light intravenous sedation added in particularly
      anxious patients. The repair was achieved by insertion of a polypropylene dart
      plug sutured to the margins of the hernial defect. RESULTS: All patients were up
      and about straightaway and were discharged within 24 hours of surgery.
      Postoperative pain was mild and required hospital analgesia in only 19% of cases
      and domiciliary analgesia in 24%. During a follow-up ranging from 6 to 60 months
      (mean 30), only one recurrence has been recorded. CONCLUSIONS: This tension-free
      technique allows immediate rehabilitation, with few complications and a low
      recurrence rate.

PMID- 11832853
TI  - Continuous monitoring of arterial blood gases and pH during laparoscopic
      cholecystectomy using a Paratrend sensor.
AB  - BACKGROUND: The safety of laparoscopic procedures has been studied broadly. The
      effects on cardiopulmonary function and reliable methods of monitoring
      concentrate more interest. METHODS: A prospective study in 22 consecutive
      patients with ASA I and II was designed. The continuous assessment of alterations
      of arterial blood gases, pH, arterial pressure and heart rate during laparoscopic
      cholecystectomy by carbon dioxide pneumoperitoneum American technique was
      achieved using an intra-vascular multi-parameter sensor Paratrend. RESULTS:
      Statistically significant increase of both PaCO2 and PE.CO2 in parallel and a
      corresponding decrease of pH were found in correlation with the duration of the
      pneumoperitoneum. The values of PaO2, Sat O2, base excess, H-CO3, mean arterial
      pressure and heart rate showed no statistically significant alterations at any
      time throughout the procedure. No differences were noted between younger patients
      and in the elderly or between patients with ASA I and II. CONCLUSIONS: Intra
      arterial blood-gas sensor ensures continuous on-line monitoring, but no abnormal
      and threatening changes occur during laparoscopic cholecystectomy in otherwise
      healthy people.

PMID- 11832854
TI  - Laparoscopic diagnostic exploration of the vaginal processus in the pediatric
      age. Preliminary experiences.
AB  - BACKGROUND: Laparoscopic surgical procedures, employed even in the paediatric
      age, bearing both diagnostic and therapeutic value, are currently used in the
      evaluation of peritoneal-vaginal duct patency during surgery for controlateral
      inguinal hernia or other diseases requiring opening of abdominal wall. METHODS:
      From January 1996 to December 2000, at the Department of Pediatric Surgery of the
      University of Siena a prospective study protocol has been performed to evaluate
      the effectiveness of laparoscopy versus traditional surgery in showing patency of
      peritoneal-vaginal duct. RESULTS: From our study we have been able to see how
      this laparoscopic procedure is well tolerated by children and parents, and is
      lacking in clinical complications. Patency of peritoneal-vaginal duct has been
      pointed out in 21.73% of cases. This result is in line with the international
      literature; in fact, the majority of authors have found a negative controlateral
      exploration in 50-80% of patients examined, thus confirming the uselessness of
      routine surgical controlateral inguinal exploration in hernia cases. CONCLUSIONS:
      The use of diagnostic laparoscopy in the study of peritoneal duct patency is a
      rapid and relatively easy technique, practically without intra- and peri
      operative risks. It allows an easy solution of the diagnostic doubt, without the
      need to necessarily perform a traditional explorative surgical procedure.

PMID- 11832855
TI  - [Intestinal carcinoma in Crohn's disease. Report of four cases and review of the
      literature].
AB  - BACKGROUND: Increasing numbers of intestinal carcinomas in patients affected by
      Crohn's disease have been reported by several authors, even if the strength of
      this associations (age, longstanding of the disease, its characteristics and
      distribution) still has to be elucidated. METHODS: From January 1992 to July
      2000, 130 patients with Crohn's disease were submitted to surgery. RESULTS: Four
      patients showed an associated intestinal carcinoma at operation, in 3 cases
      located in the ileum, and in 1 case in the colon. Patients' mean age was 54
      years. Mean duration time of the Crohn's disease was 7 years. One patient died 3
      months after surgery for disseminated peritoneal carcinomatosis, whereas 3
      patients are still alive with malignancy free at 5, 8, and 11 years after the
      tumor resection. CONCLUSIONS: These results suggest the difficulty in recognizing
      patients with Crohn's disease who are at risk for intestinal carcinoma.
      Longstanding disease, previous intestinal exclusion surgery, enterocutaneous or
      other types of fistulas should be considered for the development of cancer.
      Therefore, the prognosis may be good if early diagnosis and treatment are made.

PMID- 11832856
TI  - [Levels of cytokines in mucosal biopsies of Crohn's colitis. Physiopatological
      observations].
AB  - BACKGROUND: It is well known that mucosal concentrations of many pro and anti
      inflammatory cytokines are elevated in diseased segments of colon in Crohn's
      colitis. The present study, showing preliminary results, aims to determine
      whether the IL-1beta, IL-6 and IL-8 levels are increased throughout the entire
      colon in patients with Crohn's colitis. METHODS: Five patients with active
      Crohn's colitis and five controls were studied by mucosal biopsies. In the
      diseased patients IL-1beta, IL-6 and IL-8 levels have been measured in both
      pathologic and normal appearing colonic mucosa. The concentration of these
      cytokines was assessed using ELISA and compared. Histological sections were also
      performed to confirm diseased segment of colon. RESULTS: The concentrations IL
      1beta and IL-8 were much more higher in patients with Crohn's colitis when
      compared to controls. Moreover IL-1beta and IL-8 were more elevated in uninvolved
      colonic segments than on diseased segments. CONCLUSIONS: Our results confirm the
      finding of other authors that, although Crohn's colitis is a segmental disease,
      the concentration of IL-1beta and IL-8 in mucosal biopsies is increased
      throughout the entire colon. In particular our study shows that the
      concentrations of IL-1b and IL-8 is higher in uninvolved than involved colonic
      segments. These appearances favour the physio-pathologic hypothesis that Crohn's
      colitis involves the entire colon even when is not clinically or histologically
      apparent, and they suggest that uninvolved parts of colon may not be free of
      disease. Further studies are required to better understand the higher levels of
      cytokines found in macroscopically normal when compared to pathological mucosal
      in patients with Crohn's colitis.

PMID- 11832857
TI  - [Spontaneous and postoperative bile peritonitis. Surgical technique].
AB  - BACKGROUND: Bile peritonitis has a diversified aetiology that can present in
      clinical pictures of variable gravity depending on whether the bile is
      uncontaminated or activated by other secretions (intestinal, pancreatic) or
      actually infected. The consequent treatment is therefore eclectic. In our
      opinion, however, the therapeutic strategy proves effective if modulated on the
      basis of certain priority elements that should be carefully considered. The type
      of treatment adopted in relation to immediate and long-term results has been
      evaluated. METHODS: The investigation was carried out retrospectively on the
      series of bile peritonitis treated at the Surgical Clinic of the University of
      Modena from 1980 to 1998. 45 cases of bile peritonitis are reported of which: 32
      postoperative, 2 post-traumatic, 2 following transparietohepatic injection, 7
      during acute necrotic cholecystitis, 2 following spontaneous perforation of the
      biliary tree. As regards the type of treatment, in 13 cases (well-drained
      postoperative forms) a conservative solution was adopted; in another 13 cases (9
      septic and 4 with mixed bile supply) surgery was resorted to again, in the
      remainder transparietohepatic drainage was carried out in association almost
      always with the application of a transpapillary endoprosthesis. RESULTS:
      Morbility was 26.6% (12 cases); 4 patients (8.8%) were reoperated for late
      complications with mortality of 50%. Total mortality was 20% (9 patients).
      CONCLUSIONS: Treatment of bile peritonitis may be eclectic but the complex forms
      benefit from early surgical or parasurgical treatment for a definitive resolution
      of this feared complication.

PMID- 11832858
TI  - [Fine needle cytology ultrasound guide in breast disease. Personal experience].
AB  - BACKGROUND: The authors present their experience of diagnostic technique
      performed with an ultrafine needle. This technique utilizes simple and economical
      instrumentation. The objectives of the present work are to: improve patient
      comfort and compliance; reduce the number of inadequate cells; demonstrate the
      validity of the diagnostic method used. METHODS: In our research, 137 cases of
      both benign and malignant disease were analyzed between January 1998 and April
      2000. A further 118 cases, derived from our previous clinical trials, were added
      to these results. To achieve these objectives, the classic technique was modified
      using ultra-fine needles. In the present work, the results of the second trial
      are reported (January 1998 to April 2000) together with those from the first
      (January-December 1997). RESULTS: We have demonstrated that the technique with
      the ultra-fine needle is comparable to methods described in the world literature,
      and that the final results are equal to those of the major researchers.
      CONCLUSIONS: The advantage of this method is to be found in the small number of
      inadequate cells produced, due to the simplicity of the execution and the
      instruments, to acceptability of the examination to the patients, and to the
      overall results, which are comparable to those of major researchers. The main
      disadvantage relates to the characteristics of the needle, which is fine and
      short, and therefore unsuitable for use with deeply-placed tumors.

PMID- 11832859
TI  - [Evaluation of the tolerability of Hydrogel breast implants: a pilot study].
AB  - BACKGROUND: During the 90s the widely publicised controversy regarding the use of
      silicone gel breast implants stimulated research into alternative alloplastic
      filling materials. In this context, a new type of breast implant, containing
      Carboxymethylcellulose at 3.7% in the form of Hydrogel, was introduced into the
      European market. METHODS: A preliminary pilot study was carried out to evaluate
      the tolerability and reliability of breast implants pre-filled with Hydrogel. A
      group of 12 consecutive patients was recruited for this purpose and underwent
      plastic surgery for breast augmentation or reconstruction (20 implants) at the
      Department of Plastic and Reconstructive Surgery at the University of Genoa
      between December 1996 and October 1997. All patients were then followed up for a
      minimum of 3.5 years. The mean age of patients was 50 years and ranged from 28 to
      67 years old. After surgery the patients were examined at 4 weeks (evaluation of
      any immediate complications), 3 months, 6 months and 1 year (evaluation of any
      delayed complications). RESULTS: No immediate complications were reported in any
      patient. After 3.5 years of follow-up, the degree of capsular contraction
      according to Baker in these patients varies between 1 and 2. In general, the
      implants were very soft to touch even some time after surgery, above all in
      patients undergoing breast augmentation. Four implants (20%) were removed from 3
      patients for reasons unconnected to the implants themselves (because of neoplasm
      in one case and due to inadequate volume in the other two patients). No case of
      rupture has been reported. CONCLUSIONS: This pilot study appears to confirm the
      validity of implants prefilled with Hydrogel in reconstructive or cosmetic breast
      surgery. A larger population and longer periods of minimum follow-up are
      obviously required to confirm these results over the long term.

PMID- 11832860
TI  - Procalcitonin as an early marker of postoperative infectious complications.
AB  - BACKGROUND: Procalcitonin (PCT) is a new marker for severe infection that is
      supposed to have a useful role in the early detection of bacterial infection in
      the perioperative period. AIM OF THE STUDY: to test the hypothesis that PCT is
      useful as an early marker of postoperative infectious complications. METHODS:
      Thirty-three patients were submitted to major abdominal interventions that
      comprehend an intestinal resection (mean age: 49.9+/-19.3 years; 19 males, 14
      females). PCT was tested at 4 times: T1=preoperative; T2=6 hours after starting
      interventions; T3=24 hours after; T4=48 hours after. STATISTICAL: "t"-Student
      test and Pearson correlation. RESULTS: In the postoperative course 11 patients
      had infectious complications that were: 3 wound infections, 2 positive
      haemocolture, 1 pneumonia, 3 deep abdominal infections, 2 anastomotic
      dehiscences. In these patients only the 24 hours PCT assay at T3 was higher than
      in the other patients that had not complications (microgram/ml 4.74+/-3.8 vs
      1.22+/-0.8; p<0.0001). The cut off value of 1 ng/ml has a sensibility of 70% and
      a specificity of 81%. CONCLUSIONS: PCT detection appear to be an important aid
      for early diagnosis of postoperative infectious complications when it is used
      with the other indexes.

PMID- 11832861
TI  - [Hereditary non polyposis colorectal cancer (HNPCC). A clinical and genetic
      entity].
AB  - The first description of hereditary non polyposis colorectal cancer goes back to
      Warthin's study in 1895. In 1966 two families with autosomal dominant
      predisposition to colon and endometrial cancer were found. This condition was
      defined initially as familial neoplasm syndrome, then Lynch syndrome, and at last
      hereditary non polyposis colorectal cancer (HNPCC). HNPCC is classically
      subdivided into Lynch syndrome I (characterized by predisposition to colorectal
      cancer with early age of onset, to cancer of the proximal colon, and excess of
      synchronous and metachronous cancer), and Lynch syndrome II (characterized by
      similar colic phenotype with augmented risk of extracolonic neoplasm). If all
      clinical characteristics are present, it is possible to suspect HNPCC: however,
      diagnosis is difficult. Histological and genetic features of colon cancer confirm
      the diagnosis of HNPCC. Surgical therapy of colic neoplasm is total colectomy. A
      careful screening of HNPCC family members is one of the cardinal point in
      prevention. Follow-up of these surgical patients is the same as for sporadic
      neoplasms.

PMID- 11832862
TI  - [Breast inflammations: clinical observations and principles of treatment].
AB  - In this study some clinical and etiopathogenetic principles, and the most
      appropriate treatment for breast inflammation are discussed. In the majority of
      cases, differential diagnosis is made not only through clinical diagnosis but
      also through cytological examination and ultrasonography. Of the forms reported,
      we considered the different inflammatory, glandular and extraglandular,
      peripheral and central mastites; among the latter in particular periductal
      mastitis and duct ectasia. Medical treatment is the answer for some forms, while
      for others, as for example mammillary fistula, we prefer, in agreement with some
      authors, the surgery of fistulectomy and healing by first intention; for the
      peripheral abscesses we prefer US-guided percutaneous drainage. This article
      stresses the importance of clinical diagnosis, pathogenetic history, and adequate
      treatment in efforts to improve both the knowledge of the surgeon and the quality
      of life of the patient.

PMID- 11832863
TI  - [Caroli's disease. A case report].
AB  - Personal experience in the treatment of a patient, presenting a pure unilobar
      Caroli's disease, is described. According on the litterature data, the procedure
      of choice was the left hepatectomy. The main reason was the high incidence of
      malignant transformation to cholangiocarcinoma of the cells of the cystic walls.
      Up to now the follow-up of the patient seems to prove that it was the right
      indication. Other procedures are discussed.

PMID- 11832864
TI  - [The role of continent perineal colostomy in surgical emergencies of the distal
      bowel].
AB  - Diverting colostomy is commonly required in surgical emergencies of the distal
      colon, especially if the patient is in poor condition. This paper shows that the
      colostomy could be unnecessary in most cases. In the last 10 years, 6 patients (4
      with high-risk or postoperative complicated Hirschsprung disease, 1 with
      intestinal neuronal dysplasia and 1 with iatrogenic rectal stenosis obstruction)
      have been submitted to primary continent perineal colostomy-modified Duhamel's
      procedure. The modified technique consists of the exteriorization of the normal
      colon or ileum by a retrorectal and trans-anal way, while the excision of
      redundant tissue and rectal spur section are postponed at least for 10 days. In
      personal experience this peculiar surgical approach allows to avoid not only the
      complications due to the fashioning of a contraindicated primary anastomosis, but
      even those due to stomy performance and its closure, promoting good anatomo
      functional results in all patients. The advantages of modified Duhamel's
      operation compared to other procedures (Swenson-Pellerin or Soave pull-through)
      depend on the rapidity of execution and on the quality of short and long term
      outcome.

PMID- 11832865
TI  - Pitfalls in surgical resuscitation.
AB  - Timing of diagnosis and intervention, together with understanding of physiology
      and knowledge of anatomy, are essential for success in the practice of surgery in
      general, and emergency surgery in particular. Either excess of treatment, for
      example fluid overload in tamponated haemorrhage such as a ruptured
      retroperitoneal Abdominal Aortic Aneurysm, or defect of treatment such as delayed
      arrest of life threatening bleeding from a transected Superficial Femoral Artery
      above the knee, can both lead to disastrous outcome or death. Proximal control of
      damaged arteries is an obligatory step before repair and in emergency situations
      must be effected rapidly: the femoral artery can be easily aggressed at the groin
      under local anaesthesia; the abdominal aorta can be rapidly controlled with
      digital compression at the hiatus through the avascular area of the gastrohepatic
      ligament.

PMID- 11832866
TI  - [Internet: a fundamental tool for the retrieval of the information useful for
      medical research and health care in oncology].
AB  - Internet represents an essential aid for the professional updating of physicians
      and researches. Also for the research and therapy in oncology, Internet provides
      important such as bibliographic data, trials and guidelines with full text, as
      well as epidemiologic and statistical data. Some of the most authoritative sites
      are indicated.

PMID- 11832867
TI  - Energy expenditure during an ultra-endurance cycling race.
AB  - BACKGROUND: The energy expenditure of cycling has been investigated in great
      detail, mainly during trials performed for relatively short periods of time and
      under well established conditions. The number of investigations performed on long
      lasting races, however, is very limited, probably because of practical
      difficulties. The aim of the present work was an attempt to estimate the energy
      requirements of 5 amateur cyclists who participated in an ultra-endurance long
      lasting road cycling race. METHODS: A generalized equation obtained from
      literature was applied to calculate the energy expenditure of 26 to 137 short
      fractions of the competition. RESULTS: The calculated time weighted net metabolic
      power output ranged from 6.4 W x kg-1 to 10.8 W x kg-1; the corresponding net
      energy expenditure per unit distance ranging from 73.1 kJ x km-1 to 110.5 kJ x km
      1. The total energy expenditure of the competition (rest included) ranged from
      44.2 to 186.4 MJ, depending on the total competition duration. For all subjects,
      the sum total of the overall energy expenditure increased as a power function of
      cumulated performance time (kJ = 4872 x t0.77). However, the daily energy
      expenditure decreases with increasing the duration of the competition.
      CONCLUSIONS: It is concluded that it is possible to estimate the energy
      expenditure of ultra-endurance cycling performances, provided that the mechanical
      power output can be described by well defined equations.

PMID- 11832868
TI  - Physiological responses at 0% and 10% treadmill incline using the RPE estimation
      production paradigm.
AB  - BACKGROUND: This study examined physiological responses during 0% and 10%
      inclined treadmill exercise at prescribed ratings of perceived exertion (RPE)
      using the perceptual estimation-production paradigm. METHODS: RPE's were
      estimated during a Bruce treadmill test to volitional exhaustion. Subjects then
      produced individually prescribed RPE's (associated with 50% and 70% VO2max)
      during level (0% grade) and inclined (10% grade) treadmill exercise. Heart rate
      response (HR) and oxygen consumption (VO2) were compared between estimation
      (EST), level production (LPR), and incline production (IPR) trials using one-way
      repeated measures ANOVA. Results were considered significant at < or = 0.05.
      RESULTS: At 50% VO2max, HR and VO2 were not significantly different between EST
      (134 +/- 13 b x min-1, 27.1 +/- 5.6 ml x kg x min-1) and IPR (139 +/- 18 b x min
      1, 30.6 +/- 11.2 ml x kg x min-1). However, HR and VO2 during LPR (123 +/- 20 b x
      min-1, 24.3 +/- 8.8 ml x kg x min-1) were significantly lower than IPR. For 70%
      VO2max, HR and VO2 were not significantly different between EST (168 +/- 9 b x
      min-1, 42.1 +/- 9.4 ml x kg x min-1) and IPR (169 +/- 14 b x min-1, 41.1 +/- 10.2
      ml x kg x min-1). However HR and VO2 during LPR (155 +/- 17 b x min-1, 35.1 +/-
      8.1 ml x kg x min-1) were significantly lower than during EST and IPR.
      CONCLUSIONS: Results suggest physiological responses during RPE estimation
      production trials correspond better when estimation and production trials were
      performed at a similar treadmill incline. For exercise prescription purposes, RPE
      estimations made during inclined treadmill exercise may require adjustments to
      achieve appropriate intensities during level treadmill exercise.

PMID- 11832869
TI  - Changes in selected fitness parameters following six weeks of snowshoe training.
AB  - BACKGROUND: Recently, there has been an increase in popularity and participation
      in the sport of snowshoeing. While the sport has gained considerable recognition,
      to date there is little or no scientific research regarding training responses to
      snowshoeing as a form of exercise. Therefore, the purpose of this study was to
      determine whether snowshoe training could improve fitness measures. A further
      purpose was to compare responses from a snowshoe training program to a similarly
      designed run training program. METHODS: This prospective, comparative study was
      conducted with healthy males and females between the ages of 19 and 24. These
      subjects were recruited from the University of Vermont population and surrounding
      community. Following baseline measurements in VO2max, running time to exhaustion
      (RTE), and anthropometry, 17 subjects (10 snowshoers and 7 runners) participated
      in a six week conditioning program. Both groups exercised for 30 min at 75-85%
      age predicted maximum heart rate, 3-4 times per week, for a total of 18 sessions.
      RESULTS: VO2max improved significantly in both running and snowshoeing groups,
      6.3 and 8.5%, respectively. Run time to exhaustion also improved significantly in
      both groups, 23.3 and 33.5%, respectively. There were no changes in anthropometry
      for either group. With the exception of RTE, there were no statistically
      significant differences between groups in any other measurements at baseline.
      CONCLUSIONS: These results support the acceptability of snowshoeing as a valid
      means to improve or maintain cardiovascular endurance.

PMID- 11832870
TI  - Muscle activation and torque development during maximal unilateral and bilateral
      isokinetic knee extensions.
AB  - BACKGROUND: The aim of this study was to investigate whether or not a bilateral
      strength deficit occurs during bilateral (BL) velocity controlled dynamic knee
      extensions and if the neural control of the knee extensors and flexors is altered
      during homologous muscle BL efforts. METHODS: Twenty-eight healthy and habitually
      active subjects, 13 female and 15 male, performed maximal unilateral (UL) and BL
      isokinetic leg extensions at a velocity of 60 degrees.s-1 through a 90 degrees
      range of motion of the knee joint (90 to 180 degrees). Knee extension torque and
      electromyographic activity (EMG) of the quadriceps and hamstrings muscles were
      recorded. RESULTS: The mean knee extensor torque produced in the BL condition
      (168 +/- 52 Nm) was 17% less than the sum of the two UL conditions (Sigma=202 +/-
      56 Nm). During BL conditions, quadriceps EMG activity was less in both legs
      (left, 8.2 +/- 7.4% less and right, 13.9 +/- 9.1% less, respectively). There were
      no significant differences between BL and UL efforts for either left or right
      hamstrings activity. Eighteen subjects, who when asked to perform a maximal knee
      extension simultaneously activated their contralateral hamstrings, had
      significantly higher bilateral deficits (21%) compared to those who exhibited
      little or no contralateral hamstrings EMG activity (14%). CONCLUSIONS: The main
      findings of the study were that a bilateral strength deficit occurred when
      simultaneously maximally activating the homologous knee extensor muscles. This
      deficit was in all likelihood due to a less than maximal efferent drive to the
      quadriceps muscles. Hamstrings EMG activity was not greater during the BL knee
      extensions, which supports the notion that antagonistic muscle activity was not
      primarily responsible for the observed bilateral deficit.

PMID- 11832871
TI  - Plasma lactate recovery from maximal exercise with correction for variations in
      plasma volume.
AB  - BACKGROUND: To compare plasma lactate concentrations and plasma lactate kinetics
      during recovery, for measured and corrected values for changes in plasma volume,
      after a maximal aerobic exercise. METHODS: Sixteen male subjects performed an
      incremental and maximal exercise in order to reach maximal aerobic power. Prior
      to the exercise, at the end and during recovery (2, 5, 12 and 30 min), blood
      samples were collected through an antecubital catheter. Samples were analysed for
      lactate, hematocrit and hemoglobin in order to calculate changes in plasma
      volume. Plasma lactate concentrations ([La]p) were corrected for changes in
      plasma volume. Plasma lactate kinetics was estimated through the ratio between
      [La]p after 5 min recovery minus [La]p after 30 min to time (25 min) and
      expressed in percentage per minute. RESULTS: Maximal changes in plasma volume (
      19.7 +/- 3.8%) were correlated to maximal measured [La]p (r=0.66, p<0.01).
      Maximal measured [La]p values (14.9 +/- 2.6 mmol x l-1) were 17.3% higher
      (p<0.001) than corrected values (12.7 +/-2.0 mmol x l-1). The kinetics of [La]p
      decrease was significantly higher (p<0.001) for measured values (2.38 +/- 0.29 %
      x min-1) than for corrected values (2.22 +/- 0.33 % x min-1). CONCLUSIONS: These
      results suggested that changes in plasma volume must be taken into account when
      peak postexercise plasma lactate concentration or lactate recovery curves are
      analysed.

PMID- 11832872
TI  - A moderate carbohydrate and fat diet does not impair strength performance in
      moderately trained males.
AB  - BACKGROUND: The purpose of this investigation was to study the effects of varied
      levels of dietary carbohydrate and fat intake on exercise training and high
      intensity exercise performance in moderately strength trained, aerobic trained
      and untrained males. METHODS: Subjects (6 strength trained, 6 aerobically trained
      serving as an active control group, 6 sedentary) consumed isoenergetic diets
      considered either high CHO/low fat (HC/LF: total energy 62% CHO, 20% fat, 18%
      protein) or moderate CHO and fat (MC/MF: total energy 42% CHO, 40% fat, 18%
      protein) in a randomly assigned crossover design. Each dietary treatment was
      three weeks in length. Prior to the study and following each dietary treatment,
      muscular strength and endurance was determined (isokinetic knee extension and
      flexion, standard concentric free weight bench press). RESULTS: No differences as
      a result of the dietary treatment were seen in isokinetic peak torque, total work
      production, single repetition maximum (1 RM) bench press, or number of bench
      press repetitions at 80% 1 RM. Self-reported exercise log data showed no dietary
      effect on the subject's ability to maintain training level. CONCLUSIONS: These
      findings indicate that varying dietary macronutrient content (HC/LF or MC/MF) had
      no effect on exercise training or strength exercise performance in moderately
      trained (aerobic and strength) or sedentary males.

PMID- 11832873
TI  - The influence of transient change of total body water on relative body fats based
      on three bioelectrical impedance analyses methods. Comparison between before and
      after exercise with sweat loss, and after drinking.
AB  - BACKGROUND: The purpose of this study was to clarify the influence of change of
      total body water caused by exercise and drinking, on relative body fat (%BF)
      based on three bioelectrical impedance analyses (BIA) methods, between hand and
      foot (H-F), between hand and hand (H-H), and between foot and foot (F-F).
      METHODS: The subjects were 30 Japanese healthy young adults aged 18 to 23 years
      (15 males, 15 females). Measurements were made three times for each BIA method;
      before and after exercise with sweat, and after drinking, and also twice
      according to the under water weighing (UW) method, before exercise and after
      drinking. A pedaling exercise, with a bicycle ergometer, was used for 60 minutes
      as the exercise. RESULTS: The relationship of %BF between the UW method and each
      BIA method was mid-range or more (r=0.765-0.839). However, %BF based on the H-F
      and F-F BIA methods were higher than that based on the UW method. After drinking,
      %BF of all the BIA methods were higher than the UW method. %BF of the BIA methods
      after exercise indicated values lower than those before exercise. %BF of the H-F
      and H-H BIA methods after drinking were a little higher than those before
      exercise, indicating that those measurements reflect a slight change of body
      water. CONCLUSIONS: It was demonstrated that %BF of any BIA method reflect the
      change of body water caused by exercise, sweating, and drinking.

PMID- 11832874
TI  - Body composition estimations by BIA versus anthropometric equations in body
      builders and other power athletes.
AB  - BACKGROUND: Two main questions are stated: 1) are BIA and anthropometric
      equations accurate in estimating body composition in male power athletes and more
      specifically in body builders and 2) is there a difference in body composition
      when body builders are compared to weight and power lifters? METHODS: 
      EXPERIMENTAL DESIGN: this is a descriptive, comparative study on a selected
      sample of power athletes. PARTICIPANTS: 49 Belgian elite and sub-top male power
      athletes (34 body builders and 15 weight and power lifters) were included in this
      sample. More than 70% was in preparation of competition at time of data
      collection. MEASURES: an extended set of anthropometric measures was taken. Body
      composition was estimated by BIA (Bioelectrical Impedance Analysis) and by
      regression equations of skinfolds. Somatotype and muscle+bone areas were
      calculated. Factor analysis on all anthropometric measures was carried out to
      determine the body structure of the athletes. RESULTS: Compared to external
      visual criteria, the equations of Durnin and Womersley and Lohman (skinfolds) and
      the Guo-equation (BIA) were the only equations that could accurately estimate the
      body composition for this specific group of athletes. However, the sum of
      skinfolds attains the most accurate estimate of subcutaneous fatness. Body
      builders have significantly (p<0.01) larger arm and thigh circumferences and are
      more mesomorfic than the other power athletes (5.9 vs 3.8). CONCLUSIONS: This
      study shows that to estimate body composition in extreme power athletes BIA is
      not as accurate as compared to anthropometric equations. Moreover, the sum of a
      larger set of skinfolds is preferred to anthropometric prediction equations. In
      addition, body builders are more muscular and leaner than other power athletes.

PMID- 11832875
TI  - Physiological responses to weight-loss intervention in inactive obese African
      American and Caucasian women.
AB  - BACKGROUND: The physiological responses of inactive obese premenopausal African
      American and Caucasian women to the identical exercise training and behavior
      modification program were compared. METHODS: Inactive obese (96.1+/- 2.9 kg,
      BMI=34.8 +/- 0.7 kg/m2, % body fat=46.0 +/- 0.8; mean +/- SEM) premenopausal (36
      +/- 2 yrs) African-American (n=10) and Caucasian (n=19) women were included.
      Resting metabolic rate (RMR), respiratory exchange ratio (RER), and maximal
      aerobic power (VO2max) were measured by indirect calorimetry, and body
      composition by plethysmography. Resting and maximal heart rates, blood glucose
      and lipids, and blood pressure were also measured. Treatment consisted of a 13
      week diet and exercise behavior modification program. Group mean comparisons were
      made with a Student's "t"-test or an ANCOVA, which controlled for individual
      differences in body mass and lean body mass (LBM). Significance was set at
      p<0.05. RESULTS: Initially, the groups were not significantly different in
      height, mass, BMI, age, % body fat, fat mass, LBM, girth measurements, RMR, RER,
      VO2max, blood pressure, or cholesterol profile. The number of weeks completed,
      number of exercise sessions completed, total minutes of exercise for the entire
      intervention, average minutes of daily exercise, and total estimated exercise
      energy expenditure were all similar between groups. Furthermore, both groups
      reported similar dietary compliance. Both groups reduced body mass, BMI, LBM,
      girth measurements, and increased VO2max (mlO2 x kg-1 x min-1) significantly and
      similarly. CONCLUSIONS: African-American and Caucasian women respond the same
      physiologically to weight loss intervention. The higher prevalence in obesity for
      African-American women is not due to a different physiological response to diet
      and exercise.

PMID- 11832876
TI  - Nutritional status and body composition of juvenile elite female gymnasts.
AB  - BACKGROUND: The purpose of this study was to examine body composition, dietary
      intake and energy expenditure in 12 young female elite gymnasts aged 10.1 +/- 0.3
      years, doing a physical exercise of 15 hrs x week-1. The results were compared
      with a control group consisting of nine volunteer school girls age matched doing
      less than 4 hrs x wk-1 of physical exercise. METHODS: Assessments included
      dietary intake for 7 days, anthropometric measurements (body weight, height, arm
      circumference, triceps and subscapular skinfolds, body mass index). Body fat
      percentage was estimated using the Slaughter equation. Anthropometric
      measurements and nutritional intake were recorded in autumn. RESULTS: The
      gymnasts were shorter and had lower body weight compared with controls (p<0.05).
      Percentage of body fat was significantly lower in gymnasts versus controls
      (p<0.01). Gymnasts had higher percentage of fat free mass (p<0.01) than the
      reference group. Daily energy intake met daily energy requirement in both groups.
      Distribution of energy for both groups was almost identical, with approximately
      14% from protein, 48% from carbohydrate, and 37% from fat. The average intakes of
      polyunsaturated fat were low in the two groups. The main daily intake of most
      nutrients in both groups were in accordance with recommendations; exceptions were
      dietary fibre, E and B6 vitamins. CONCLUSIONS: The primary finding of this
      investigation is that in both groups, the mean daily energy intake met the energy
      requirement. Thus, the gymnasts did not restrict total energy. The overall
      nutrient intake of the two groups may appear adequate. Prepubertal gymnasts have
      higher percentage of fat free mass and daily energy expenditure and dietary
      intakes, but lower percent body fat than age matched controls.

PMID- 11832877
TI  - Bench/step training with and without extremity loading. Effects on muscular
      fitness, body composition profile, and psychological affect.
AB  - BACKGROUND: To study the effect of bench/step group exercise with and without
      extremity loading on muscular fitness, body composition, and psychological
      affect. METHODS:  EXPERIMENTAL DESIGN: a prospective training study. SETTING:
      general community fitness center. PARTICIPANTS: 44 healthy adult females (age: 21
      51 yrs). INTERVENTIONS: 12 weeks of bench/ step exercise (3 sessions/week, 50
      min/session, 60-90% HRmax). Subjects were randomly assigned to groups that
      trained with (WT, n=16) and without (NWT, n=16) 0.68 kg/ankle and 1.36 kg/hand
      weights while 12 subjects served as non-training controls (NTC). MEASURES: Pre-
      and postintervention muscular strength and endurance for knee and elbow flexion
      and extension, and for shoulder abduction and adduction were examined by
      isokinetic dynamometry. Body composition was assessed with hydrostatic weighing
      and psychological affect by questionnaire. RESULTS: Thirty-two subjects completed
      the study. ANOVA revealed that pre- to postintervention changes for body fat
      (2.6%), fat-free weight (+0.7 kg), fat weight (-1.9 kg), and knee flexion peak
      torque were significantly different in the bench/step exercise trained (WT+NWT)
      compared to the NTC study group. Specific comparisons of muscle strength and
      endurance change scores of WT+NWT relative to NTC, and of WT relative to NWT
      revealed no other significant differences between groups. Positive and negative
      affective states were similar among study groups before and after the
      intervention. CONCLUSIONS: Participation in bench/step group exercise improved
      body composition but was of limited or no value as a modality to change muscular
      fitness and psychological affect in healthy adult females. The use of ankle and
      hand weights failed to enhance training adaptations.

PMID- 11832878
TI  - Heart rate variation after breath hold diving with different underwater swimming
      velocities.
AB  - BACKGROUND: The aim of this study was to demonstrate the kinetics of heart rate
      and blood lactate level obtained after repeated short breath holds with muscular
      effort in a swimming pool. METHODS:  EXPERIMENTAL DESIGN: each subject had to
      perform a series of breath hold diving at rest and three series for different
      underwater swimming velocities. A series corresponded to six dives of a 30 sec
      duration separated by a recovery period of 30 sec. Heart rates and blood lactate
      levels were measured at rest and at the end of each series of breath holds.
      PARTICIPANTS: the population was composed of 10 male subjects divided into one
      trained group (5 experts) and one group of 5 beginners. RESULTS: Results
      indicated a higher bradycardia for the expert group at static breath hold (54.25
      vs 65.5 beats x min-1). At the end of a series of breath holds, tachycardia was
      higher for beginners at different underwater swimming velocities. These values
      were less significant than the heart rate measured in laboratory despite trials
      that were abandoned due to high blood lactate levels above 3.5 mmol x l-1. In
      order to avoid the breath hold breaking point, the maximum heart rate had to
      correspond to the heart rate of the ventilatory threshold measured in the
      laboratory, minus the variations of bradycardia measured at rest. CONCLUSIONS:
      For the training coach, bradycardia was determined by water immersion during a
      static breath hold. This permitted an evaluation of the level of diver training.
      A maximal heart rate was attempted to avoid the breath hold breaking point. The
      results of this study may be useful in creating an effective diver training
      program.

PMID- 11832880
TI  - Partial absence of pericardium in an endurance athlete. A case report.
AB  - A twenty-nine-year-old competitive endurance runner was noted to have a
      congenital absence of the pericardium on a routine screening exam. No
      recommendations for activity restrictions have been previously described for this
      condition. After maximal exercise performance on a cardiac stress test without
      symptoms of cardiac compromise and consultation with cardiologists and
      cardiothoracic surgeons, the patient was returned to full, unrestricted
      competitive running. Once the diagnosis of absent pericardium is confirmed by
      imaging modalities, cardiac stress testing may be employed to determine a
      recommended activity level for the patient.

PMID- 11832879
TI  - Effects of physical exercise on clinic and 24-hour ambulatory blood pressure in
      young subjects with mild hypertension.
AB  - BACKGROUND: The aim of the study was to assess the effect of physical activity on
      24-hr ambulatory blood pressure (ABPM) and office blood pressure (BP) in 572 male
      subjects with borderline to mild hypertension from the HARVEST study. METHODS:
      Subjects were 18 to 45 years old with diastolic BP of 90-99 mmHg and/or systolic
      BP of 140-159 mmHg. They never took any anti-hypertensive therapy. All subjects
      underwent physical examination, office BP measurement and two 24-hr ambulatory BP
      monitorings performed three months apart. Subjects were classified as non
      exercisers, group 1 (n=331), mild exercisers, group 2 (n=192) and heavy
      exercisers, group 3 (n=49). During the three months of follow-up subjects
      maintained the same physical activity habits. There was no difference in smoking
      and alcohol consumption between the 3 groups. As the groups differed
      significantly in age and body mass index data were adjusted for these
      confounders. RESULTS: At baseline office and ambulatory systolic BP were similar
      in the 3 groups, while diastolic BP was proportional to the level of physical
      activity although the difference was significant only between the group of non
      exercisers and mild exercisers. Heart rate (HR) was always inversely related to
      the intensity of exercise. After three months follow-up office systolic BP was
      similar among the three groups and diastolic BP slightly decreased in the
      exercisers (group 1 vs group 3 p=0.02, group 2 vs group 3 p=0.04). At ABPM the
      group of heavy exercisers showed a significant decrease in daytime systolic BP
      (135.4plus minus0.6 vs 134plus minus0.8 vs 132.2plus minus1.6 mmHg; group 1 vs
      group 3 p<0.05) and the difference between systolic ambulatory BP at the 3rd
      month and at baseline, showed an additional significant decrease according to
      exercise intensity (24-hr systolic BP group 1 vs group 3 p=0.001, group 2 vs
      group 3 p=0.004; daytime systolic BP group 1 vs group 3 p=0.0009, group 2 vs
      group 3 p=0.004; night-time systolic BP group 1 vs group 3 p=0.02, group 2 vs
      group 3 p=0.02). No changes in ambulatory diastolic BP were observed.
      CONCLUSIONS: In conclusion, physical activity has a positive effect in lowering
      BP attenuating the risk of hypertension in young subjects with borderline
      hypertension. The anti-hypertensive effect of physical activity persisted after
      three months and the group of exercisers had an additional reduction in systolic
      BP detected by ABPM. To obtain accurate information on chronic levels of arterial
      pressure over time 24-hr ambulatory BP should be preferred to traditional casual
      readings.

PMID- 11832881
TI  - Exercise-induced, persistent and generalized muscle cramps. A case report.
AB  - We are reporting on a 46-year-old man who has suffered of muscle cramps for 4
      years, occurring immediately after jogging and playing tennis and lasting for 7-8
      hours. Repeated neurological, orthopedic, internal medical and endocrinological
      examinations showed no pathological findings. Physiotherapy, supplementation of
      fluids and electrolytes had no effect, nor did medication therapy with muscle
      relaxants. During spiroergometry without medication, there was an
      overproportional increase of heart rate and respiratory rate with delayed pCO2
      increase after exercise with otherwise normal blood gas levels. This reaction was
      considerably reduced during spiroergometry under beta-blockade (metoprolol 100
      mg); at the same time, the muscle cramps could no longer be induced. Both
      excessive respiratory regulation and direct hyperadrenergic stimulation should be
      discussed as the primary cause of the muscle cramps. According to recent
      findings, b-blockers with intrinsic sympathocomimetic activity should be avoided
      in therapy.

PMID- 11832882
TI  - Stages of exercise behavior and caloric expenditure.
AB  - BACKGROUND: This study assessed the ability of the stages of exercise behavior to
      differentiate caloric energy expenditure, by stage, based upon self-report of
      energy expenditure (EE). METHODS: Volunteer male and female participants (n=890)
      reported current stage of physical activity; physical activity mode, duration,
      and frequency; and demographic information (height and weight). Data calculated
      from reported information included EE, body mass index (BMI), and BMI category.
      EE profiles were established by average estimated EE (kcal/wk), average total
      time (min/wk) for physical activity, average activity frequency (times/wk),
      average session duration (min/session), moderate and vigorous EE levels
      (kcal/wk), and categorized activity level (sedentary, moderate, vigorous).
      RESULTS: There were no significant within gender differences across stages of
      exercise behavior for height. Terminators differed significantly for weight from
      all other groups, and BMI was significantly less across groups, by gender. All
      males were identified in the "Mildly Obese" BMI level, while only females in the
      non-active (precontemplation, contemplation, and preparation) groups were so
      identified. All other females were at the "Acceptable" BMI level. Regardless of
      gender, all groups were significantly different from the sedentary
      precontemplation and contemplation group for EE. Male and female preparation
      groups reported EE in the moderate level, and were significantly different from
      the action, maintenance, and termination groups, who reported EE in the vigorous
      level. Across subsequent stages of exercise behavior, female participants
      demonstrated increased EE. Male participants were similarly profiled, with the
      exception of one group (action stage), which was considerably greater than all
      other groups. CONCLUSIONS: This study confirmed the earlier examined premise, by
      Cardinal, that self-selected stage of exercise behavior differentiates EE by
      stage.

PMID- 11832883
TI  - Neuropsychological impairment in soccer athletes.
AB  - BACKGROUND: Soccer reportedly places participants at risk for neuropsychological
      impairment, although it is unknown if the risk is associated primarily with
      concussion, subconcussive blows from heading the ball, or some combination
      thereof. Moreover, the extent to which younger versus older athletes are at risk
      for soccer-related cognitive impairment is unclear. We hypothesized that soccer
      athletes, especially older ones, would show poorer neuropsychological test
      performance than comparable swimmers. METHODS: Thirty-two soccer (26 college and
      6 professional) and 29 swimmers (22 college and 7 masters level), all involved
      for at least 4 years in their sport at collegiate or national levels,
      participated. In a 2 X 2 (sport X age category) factorial design, all
      participants underwent 4 neuropsychological tests with 11 outcome measures
      assessing motor speed, attention, concentration, reaction time, and conceptual
      thinking. RESULTS: Soccer athletes performed worse than swimmers on measures of
      conceptual thinking. The older soccer group in particular performed poorly on
      measures of conceptual thinking, reaction time, and concentration. Among non
      goaltender soccer athletes, estimates of career exposure to brain trauma (based
      on length of career and level of play) predicted significantly poorer test
      performance on 6 of 11 measures, even after statistically controlling for age.
      CONCLUSIONS: Results provide additional evidence that participation in soccer may
      be associated with poorer neuropsychological performance, although the observed
      pattern of findings does not specifically implicate heading as the cause.
      Although deficits were most apparent among older soccer players, serial
      neuropsychological testing for early detection of impairment is recommended for
      younger players as well.

PMID- 11832884
TI  - State anxiety responses to acute resistance training and step aerobic exercise
      across eight weeks of training.
AB  - BACKGROUND: The purpose of this study was to contrast state anxiety responses to
      acute aerobic and resistance exercise across an 8-week period. METHODS: State
      anxiety (STAI-Y1) was assessed immediately prior to and 5 min following 50-min
      exercise sessions in 42 adults enrolled in introductory level resistance training
      or step aerobic exercise classes. Participants were instructed to maintain an
      intensity between 70-80% of their own maximum in both exercise conditions. State
      anxiety was assessed at weeks one, four and eight of 16-week courses. RESULTS:
      Repeated measures ANOVA revealed that state anxiety decreased (p<0.05) following
      both exercise conditions (step aerobics: 36.65 to 33.03; resistance training:
      35.12 to 30.39). The magnitude of the reduction did not differ significantly
      between conditions, nor did it change from week one to week eight. Participants
      were grouped into high and low baseline state anxiety groups to determine the
      potential influence of baseline anxiety. Reductions (p<0.05) in state anxiety
      were observed for the high baseline groups (step aerobics: 49.7 to 40.4;
      resistance: 47.6 to 38.5), and following step aerobic exercise for the low
      baseline group (29.9 to 26.8). However, state anxiety did not decrease (29.6 to
      29.5) following resistance exercise in the low baseline group. CONCLUSIONS: These
      results indicate state anxiety reductions occur following 50-min of aerobic
      exercise or weight training, and responses were not altered across 8-weeks of
      training. Similar state anxiety reductions were observed for each exercise mode
      in cases with elevated baseline state anxiety values, low baseline state anxiety
      levels were significantly reduced solely in the step aerobics condition.

PMID- 11832885
TI  - Evaluation of a university course aimed at promoting exercise behavior.
AB  - BACKGROUND: This study assessed a 10-week, university-required lifetime fitness
      for health (LFH) course on students' leisure-time exercise behavior and
      advancement through the stages of change for exercise. METHODS:  EXPERIMENTAL
      DESIGN: a quasi-experimental design was employed. SETTING: public university
      located in the United States. PARTICIPANTS: a total of 540 students who were
      enrolled in an LFH course or selected psychology courses volunteered to
      participate in this study. INTERVENTION: a 30-hour LFH course administered over
      10 weeks. The course was delivered both in a lecture and lab format. The control
      condition consisted of psychology courses. MEASURES: weekly leisure-time exercise
      behavior and stage of change for exercise behavior were assessed using valid and
      reliable self-report questionnaires at pre- and post-intervention. RESULTS:
      Regardless of course, students' showed minimal changes in their exercise levels
      from pre- to post-intervention. Moreover, students in the LFH course did not
      improve their stage of change for exercise behavior as much students in the
      psychology courses. Regardless of course, participants' stage of change for
      exercise was an important moderator variable associated with exercise behavior
      change. CONCLUSIONS: As was taught, the LFH course did little to change the
      participants' exercise levels outside of class, and did little to positively
      influence the participants' stage of change for exercise behavior.

PMID- 11832889
TI  - Swings and roundabouts.

PMID- 11832886
TI  - Ultrasound changes to intramuscular architecture of the quadriceps following
      intramedullary nailing.
AB  - BACKGROUND: Disuse atrophy is the basis for profound physiological changes of the
      muscles of immobilised limbs. The aim of this study was to use high resolution
      real-time ultrasonography (HRRTU) to assess the quadriceps musculature and to try
      and measure atrophy. METHODS: We monitored the effects of enforced reduction of
      mobility due to trauma on the intramuscular architecture of the quadriceps using
      HRRTU in 13 skeletally mature male patients (43.2 years, range 16 to 82 years),
      with an isolated unilateral diaphyseal fracture of the femur or of the tibia. All
      patients had undergone interlocked intramedullary nailing (IIN). Using HRRTU, the
      pennation angles and muscle fibre lengths of vastus lateralis, the cross
      sectional area (CSA) of the rectus femoris, and the quadriceps muscle layer
      thickness (MLT) were measured in the injured and the normal contralateral limb.
      RESULTS: Repeated measurements showed the technique of measurement of the
      variables used in this study to be highly reproducible. There was a significant
      difference in the angle of pennation of the vastus lateralis in the nailed (15.4
      degree) and the unnailed limb (21.2 degree), documenting that muscle atrophy
      causes a change to muscle architecture that results in a significant decrease in
      pennation angle (p=0.0002). The muscle fibre length was significantly different
      (p=0.002) and there was a significant correlation between pennation angle and
      muscle fibre length (r=-0.51, p=0.001). There was also a significant difference
      in the quadriceps MLT (p=0.001) and CSA of the rectus femoris (p=0.0004) implying
      that the whole of the quadriceps muscle is affected. CONCLUSIONS: These simple,
      reproducible, non-invasive ultrasound measurements can easily demonstrate
      differences in the quadriceps morphology in the nailed and unnailed limb, which
      could allow individual exercise programme prescription.

PMID- 11832891
TI  - Life beyond the walls.

PMID- 11832890
TI  - A route to flexible working.

PMID- 11832892
TI  - A troublesome menage a trois.

PMID- 11832893
TI  - Awash with cash, bereft of leadership.

PMID- 11832894
TI  - Developing world gets patent aid.

PMID- 11832896
TI  - Funding freeze leaves high-energy physics facing cuts.

PMID- 11832895
TI  - National audit slams CNRS over poor management and planning.

PMID- 11832897
TI  - Bush goes to war as budget boosts R&D.

PMID- 11832902
TI  - NASA tunes in to nuclear power.

PMID- 11832904
TI  - German parliament backs stem-cell research.

PMID- 11832905
TI  - Drillers dig deep for microbes under the sea floor.

PMID- 11832906
TI  - Reviews spark debate over breast screening.

PMID- 11832910
TI  - All at sea.

PMID- 11832909
TI  - Planetary portraits.

PMID- 11832911
TI  - World hasn't changed for the dispossessed.

PMID- 11832912
TI  - The 15% solution for majority health concerns.

PMID- 11832913
TI  - Diagnostic testing fails the test.

PMID- 11832919
TI  - Coming to terms.

PMID- 11832920
TI  - Drug receptors: a long engagement.

PMID- 11832921
TI  - Brains out of tune.

PMID- 11832923
TI  - Hidden in a sea of microbes.

PMID- 11832924
TI  - An APE that proofreads.

PMID- 11832925
TI  - Taking the temperature.

PMID- 11832926
TI  - A slower flow.

PMID- 11832929
TI  - Carbon nanothermometer containing gallium.
AB  - Many applications have been found for carbon nanotubes, and we can now add a role
      as a 'nanothermometer' to this list. We describe how the height of a continuous,
      unidimensional column of liquid gallium inside a carbon nanotube (up to about 10
      micrometres long and about 75 nanometres in diameter) varies linearly and
      reproducibly in the temperature range 50-500 degrees C, with an expansion
      coefficient that is the same as for gallium in the macroscopic state. We chose
      gallium as our thermal indicator because it has one of the greatest liquid ranges
      of any metal (29.78-2,403 degrees C) and a low vapour pressure even at high
      temperatures. This nanothermometer should be suitable for use in a wide variety
      of microenvironments.

PMID- 11832928
TI  - Obituary: Franco Rasetti (1901-2001).

PMID- 11832930
TI  - Speech sounds learned by sleeping newborns.
AB  - It is not yet clear whether humans are able to learn while they are sleeping.
      Here we show that full-term human newborns can be taught to discriminate between
      similar vowel sounds when they are fast asleep. It is possible that such sleep
      training soon after birth could find application in clinical or educational
      situations.

PMID- 11832931
TI  - Spin-engineering magnetic media.
AB  - The explosion in demand for increased data-storage density is driving the
      exploration of new magnetic media. Here we describe a new type of magnetic medium
      in which the spin configurations are engineered in chemically homogeneous
      magnetic films: regularly arranged in-plane and out-of-plane spin configurations
      are defined by altering the magnetic anisotropy. These spin-engineered media not
      only maintain the surface planarity but also the homogeneity of the magnetic
      materials, and our method is likely to find immediate application on account of
      its simplicity and ease of integration.

PMID- 11832932
TI  - Communication arising. Is coral bleaching really adaptive?
AB  - From an experiment in which corals are transplanted between two depths on a
      Panamanian coral reef, Baker infers that bleaching may sometimes help reef corals
      to survive environmental change. Although Baker's results hint at further
      mechanisms by which reef-building corals may acclimatize to changing light
      conditions, we do not consider that the evidence supports his inference.

PMID- 11832936
TI  - Slowdown of the meridional overturning circulation in the upper Pacific Ocean.
AB  - Decadal temperature fluctuations in the Pacific Ocean have a significant effect
      on marine ecosystems and the climate of North America. The physical mechanisms
      responsible for these fluctuations are poorly understood. Some theories ascribe a
      central role to the wind-driven meridional overturning circulation between the
      tropical and subtropical oceans. Here we show, from observations over the past 50
      years, that this overturning circulation has been slowing down since the 1970s,
      causing a decrease in upwelling of about 25% in an equatorial strip between 9
      degrees N and 9 degrees S. This reduction in equatorial upwelling of relatively
      cool water, from 47 x 10(6) to 35 x 10(6) m3 s(-1), is associated with a rise in
      equatorial sea surface temperatures of about 0.8 degrees C. Another effect of the
      slowing circulation is a reduction in the outgassing of CO2 from the equatorial
      Pacific Ocean-at present the largest oceanic source of carbon dioxide to the
      atmosphere.

PMID- 11832937
TI  - Visual predators select for crypticity and polymorphism in virtual prey.
AB  - Cryptically coloured animals commonly occur in several distinct pattern variants.
      Such phenotypic diversity may be promoted by frequency-dependent predation, in
      which more abundant variants are attacked disproportionately often, but the
      hypothesis has never been explicitly tested. Here we report the first controlled
      experiment on the effects of visual predators on prey crypticity and phenotypic
      variance, in which blue jays (Cyanocitta cristata) searched for digital moths on
      computer monitors. Moth phenotypes evolved via a genetic algorithm in which
      individuals detected by the jays were much less likely to reproduce. Jays often
      failed to detect atypical cryptic moths, confirming frequency-dependent selection
      and suggesting the use of searching images, which enhance the detection of common
      prey. Over successive generations, the moths evolved to become significantly
      harder to detect, and they showed significantly greater phenotypic variance than
      non-selected or frequency-independent selected controls.

PMID- 11832938
TI  - Testing the thermodynamic approach to granular matter with a numerical model of a
      decisive experiment.
AB  - Edwards has proposed a thermodynamic description of dense, slowly flowing
      granular matter, in which the grains (the 'atoms' of the system) interact with
      inelastic forces and enduring contacts. In Edwards' ensemble-one of the very few
      generalizations of standard statistical mechanics-thermodynamic quantities are
      computed as flat averages over configurations in which the grains are static or
      jammed, leading to a natural definition of configurational temperature. But the
      approach is not justified from first principles and hence, in the absence of
      explicit tests of its validity, has not been widely accepted. Here we report a
      numerical experiment involving a realistic model of slowly sheared granular
      matter; our results strongly support the thermodynamic description. Considering
      particles of different sizes in a slowly sheared dense granular system, we
      extract an effective temperature from a relation connecting their diffusivity and
      mobility. We then perform an explicit computation to show that the effective
      temperature measured from this relation coincides with the Edwards
      configurational temperature. Our approach, which is specifically conceived to be
      reproducible in the laboratory, may thus render the Edwards temperature
      accessible to experiments.

PMID- 11832939
TI  - Growth of nanowire superlattice structures for nanoscale photonics and
      electronics.
AB  - The assembly of semiconductor nanowires and carbon nanotubes into nanoscale
      devices and circuits could enable diverse applications in nanoelectronics and
      photonics. Individual semiconducting nanowires have already been configured as
      field-effect transistors, photodetectors and bio/chemical sensors. More
      sophisticated light-emitting diodes (LEDs) and complementary and diode logic
      devices have been realized using both n- and p-type semiconducting nanowires or
      nanotubes. The n- and p-type materials have been incorporated in these latter
      devices either by crossing p- and n-type nanowires or by lithographically
      defining distinct p- and n-type regions in nanotubes, although both strategies
      limit device complexity. In the planar semiconductor industry, intricate n- and p
      type and more generally compositionally modulated (that is, superlattice)
      structures are used to enable versatile electronic and photonic functions. Here
      we demonstrate the synthesis of semiconductor nanowire superlattices from group
      III-V and group IV materials. (The superlattices are created within the nanowires
      by repeated modulation of the vapour-phase semiconductor reactants during growth
      of the wires.) Compositionally modulated superlattices consisting of 2 to 21
      layers of GaAs and GaP have been prepared. Furthermore, n-Si/p-Si and n-InP/p-InP
      modulation doped nanowires have been synthesized. Single-nanowire
      photoluminescence, electrical transport and electroluminescence measurements show
      the unique photonic and electronic properties of these nanowire superlattices,
      and suggest potential applications ranging from nano-barcodes to polarized
      nanoscale LEDs.

PMID- 11832940
TI  - Ultralow-threshold Raman laser using a spherical dielectric microcavity.
AB  - The ability to confine and store optical energy in small volumes has implications
      in fields ranging from cavity quantum electrodynamics to photonics. Of all cavity
      geometries, micrometre-sized dielectric spherical resonators are the best in
      terms of their ability to store energy for long periods of time within small
      volumes. In the sphere, light orbits near the surface, where long confinement
      times (high Q) effectively wrap a large interaction distance into a tiny volume.
      This characteristic makes such resonators uniquely suited for studies of
      nonlinear coupling of light with matter. Early work recognized these attributes
      through Raman excitation in microdroplets-but microdroplets have not been used in
      practical applications. Here we demonstrate a micrometre-scale, nonlinear Raman
      source that has a highly efficient pump-signal conversion (higher than 35%) and
      pump thresholds nearly 1,000 times lower than shown before. This represents a
      route to compact, ultralow-threshold sources for numerous wavelength bands that
      are usually difficult to access. Equally important, this system can provide a
      compact and simple building block for studying nonlinear optical effects and the
      quantum aspects of light.

PMID- 11832941
TI  - Observation of ligand effects during alkene hydrogenation catalysed by supported
      metal clusters.
AB  - Homogeneous organometallic catalysts and many enzymes activate reactants through
      coordination to metal atoms; that is, the reactants are turned into ligands and
      their reactivity controlled through other ligands in the metal's coordination
      sphere. In the case of supported metal clusters, catalytic performance is
      influenced by the support and by adsorbed reactants, intermediates or products.
      The adsorbates are usually treated as ligands, whereas the influence of the
      supports is usually ascribed to electronic interactions, even though metal
      clusters supported on oxides and zeolites form chemical bonds to support oxygen
      atoms. Here we report direct observations of the structure of supported metal
      clusters consisting of four iridium atoms, and the identification of hydrocarbon
      ligands bound to them during propene hydrogenation. We find that propene and
      molecular hydrogen form propylidyne and hydride ligands, respectively, whereas
      simultaneous exposure of the reactants to the supported iridium cluster yields
      ligands that are reactive intermediates during the catalytic propane-formation
      reaction. These intermediates weaken the bonding within the tetrahedral iridium
      cluster and the interactions between the cluster and the support, while
      replacement of the MgO support with gamma-Al2O3 boosts the catalytic activity
      tenfold, by affecting the bonding between the reactant-derived ligands and the
      cluster and therefore also the abundance of individual ligands. This interplay
      between the support and the reactant-derived ligands, whereby each influences the
      interaction of the metal cluster with the other, shows that the catalytic
      properties of supported metal catalysts can be tuned by careful choice of their
      supports.

PMID- 11832942
TI  - Towards robust regional estimates of CO2 sources and sinks using atmospheric
      transport models.
AB  - Information about regional carbon sources and sinks can be derived from
      variations in observed atmospheric CO2 concentrations via inverse modelling with
      atmospheric tracer transport models. A consensus has not yet been reached
      regarding the size and distribution of regional carbon fluxes obtained using this
      approach, partly owing to the use of several different atmospheric transport
      models. Here we report estimates of surface-atmosphere CO2 fluxes from an
      intercomparison of atmospheric CO2 inversion models (the TransCom 3 project),
      which includes 16 transport models and model variants. We find an uptake of CO2
      in the southern extratropical ocean less than that estimated from ocean
      measurements, a result that is not sensitive to transport models or
      methodological approaches. We also find a northern land carbon sink that is
      distributed relatively evenly among the continents of the Northern Hemisphere,
      but these results show some sensitivity to transport differences among models,
      especially in how they respond to seasonal terrestrial exchange of CO2. Overall,
      carbon fluxes integrated over latitudinal zones are strongly constrained by
      observations in the middle to high latitudes. Further significant constraints to
      our understanding of regional carbon fluxes will therefore require improvements
      in transport models and expansion of the CO2 observation network within the
      tropics.

PMID- 11832944
TI  - Sex differences in emigration and mortality affect optimal management of deer
      populations.
AB  - Populations of red deer that are limited by food, like those of many other
      ungulates, commonly include more females than males. We assessed the contribution
      of variation in sex- and age-specific rates of mortality and emigration to
      density-dependent changes in the adult sex ratio, using long-term observations
      and demographic experiments involving the red deer population on Rum, Scotland.
      We incorporated these effects in a stochastic model of local populations under
      different management regimes to show here that, when female numbers are allowed
      to increase to more than 60% of the ecological carrying capacity, the sustainable
      annual harvest of males from local deer populations will fall. Because males are
      typically culled by fee-paying hunters and generate more income than females,
      income will decrease as the male harvest falls. Because numbers of female deer
      throughout much of the Highlands probably exceed the threshold at which male
      density starts to be affected, many managers might be able to raise income from
      local deer populations by reducing female numbers, with potential benefits to the
      vegetation of Scottish Highland environments.

PMID- 11832943
TI  - Unsuspected diversity among marine aerobic anoxygenic phototrophs.
AB  - Aerobic, anoxygenic, phototrophic bacteria containing bacteriochlorophyll a
      (Bchla) require oxygen for both growth and Bchla synthesis. Recent reports
      suggest that these bacteria are widely distributed in marine plankton, and that
      they may account for up to 5% of surface ocean photosynthetic electron transport
      and 11% of the total microbial community. Known planktonic anoxygenic phototrophs
      belong to only a few restricted groups within the Proteobacteria alpha-subclass.
      Here we report genomic analyses of the photosynthetic gene content and operon
      organization in naturally occurring marine bacteria. These photosynthetic gene
      clusters included some that most closely resembled those of Proteobacteria from
      the beta-subclass, which have never before been observed in marine environments.
      Furthermore, these photosynthetic genes were broadly distributed in marine
      plankton, and actively expressed in neritic bacterioplankton assemblages,
      indicating that the newly identified phototrophs were photosynthetically
      competent. Our data demonstrate that planktonic bacterial assemblages are not
      simply composed of one uniform, widespread class of anoxygenic phototrophs, as
      previously proposed; rather, these assemblages contain multiple, distantly
      related, photosynthetically active bacterial groups, including some unrelated to
      known and cultivated types.

PMID- 11832945
TI  - Influence of scene statistics on colour constancy.
AB  - The light reflected from an object depends not only on the surface properties of
      this object but also on the illuminant. The same is true for the excitations of
      the photoreceptors, which serve as the basis for the perceived colour. However,
      our visual system has the ability to perceive constant surface colours despite
      changes in illumination. The average chromaticity of the retinal image of a scene
      depends on the illumination, and thus might be used by the visual system to
      estimate the illumination and to modulate the correction that subserves colour
      constancy. But this measure is not sufficient: a reddish scene under white light
      can produce the same mean stimulation as a neutral scene in red light. Higher
      order scene statistics-for example, the correlation between redness and luminance
      within the image-allow these cases to be distinguished. Here we report that the
      human visual system does exploit such a statistic when estimating the illuminant,
      and gives it a weight that is statistically appropriate for the natural
      environment.

PMID- 11832946
TI  - Genome shuffling leads to rapid phenotypic improvement in bacteria.
AB  - For millennia, selective breeding, on the basis of biparental mating, has led to
      the successful improvement of plants and animals to meet societal needs. At a
      molecular level, DNA shuffling mimics, yet accelerates, evolutionary processes,
      and allows the breeding and improvement of individual genes and subgenomic DNA
      fragments. We describe here whole-genome shuffling; a process that combines the
      advantage of multi-parental crossing allowed by DNA shuffling with the
      recombination of entire genomes normally associated with conventional breeding.
      We show that recursive genomic recombination within a population of bacteria can
      efficiently generate combinatorial libraries of new strains. When applied to a
      population of phenotypically selected bacteria, many of these new strains show
      marked improvements in the selected phenotype. We demonstrate the use of this
      approach through the rapid improvement of tylosin production from Streptomyces
      fradiae. This approach has the potential to facilitate cell and metabolic
      engineering and provide a non-recombinant alternative to the rapid production of
      improved organisms.

PMID- 11832947
TI  - Vesicular restriction of synaptobrevin suggests a role for calcium in membrane
      fusion.
AB  - Release of neurotransmitter occurs when synaptic vesicles fuse with the plasma
      membrane. This neuronal exocytosis is triggered by calcium and requires three
      SNARE (soluble-N-ethylmaleimide-sensitive factor attachment protein receptors)
      proteins: synaptobrevin (also known as VAMP) on the synaptic vesicle, and
      syntaxin and SNAP-25 on the plasma membrane. Neuronal SNARE proteins form a
      parallel four-helix bundle that is thought to drive the fusion of opposing
      membranes. As formation of this SNARE complex in solution does not require
      calcium, it is not clear what function calcium has in triggering SNARE-mediated
      membrane fusion. We now demonstrate that whereas syntaxin and SNAP-25 in target
      membranes are freely available for SNARE complex formation, availability of
      synaptobrevin on synaptic vesicles is very limited. Calcium at micromolar
      concentrations triggers SNARE complex formation and fusion between synaptic
      vesicles and reconstituted target membranes. Although calcium does promote
      interaction of SNARE proteins between opposing membranes, it does not act by
      releasing synaptobrevin from synaptic vesicle restriction. Rather, our data
      suggest a mechanism in which calcium-triggered membrane apposition enables
      syntaxin and SNAP-25 to engage synaptobrevin, leading to membrane fusion.

PMID- 11832948
TI  - An exonucleolytic activity of human apurinic/apyrimidinic endonuclease on 3'
      mispaired DNA.
AB  - Human apurinic/apyrimidinic endonuclease (APE1) is an essential enzyme in DNA
      base excision repair that cuts the DNA backbone immediately adjacent to the 5'
      side of abasic sites to facilitate repair synthesis by DNA polymerase beta (ref.
      1). Mice lacking the murine homologue of APE1 die at an early embryonic stage.
      Here we report that APE1 has a DNA exonuclease activity on mismatched
      deoxyribonucleotides at the 3' termini of nicked or gapped DNA molecules. The
      efficiency of this activity is inversely proportional to the gap size in DNA. In
      a base excision repair system reconstituted in vitro, the rejoining of nicked
      mismatched DNA depended on the presence of APE1, indicating that APE1 may
      increase the fidelity of base excision repair and may represent a new 3'
      mispaired DNA repair mechanism. The exonuclease activity of APE1 can remove the
      anti-HIV nucleoside analogues 3'-azido-3'-deoxythymidine and 2',3'-didehydro-2',
      3'-dideoxythymidine from DNA, suggesting that APE1 might have an impact on the
      therapeutic index of antiviral compounds in this category.

PMID- 11832949
TI  - Mechanism of force generation by myosin heads in skeletal muscle.
AB  - Muscles generate force and shortening in a cyclical interaction between the
      myosin head domains projecting from the myosin filaments and the adjacent actin
      filaments. Although many features of the dynamic performance of muscle are
      determined by the rates of attachment and detachment of myosin and actin, the
      primary event in force generation is thought to be a conformational change or
      'working stroke' in the actin-bound myosin head. According to this hypothesis,
      the working stroke is much faster than attachment or detachment, but can be
      observed directly in the rapid force transients that follow step displacement of
      the filaments. Although many studies of the mechanism of muscle contraction have
      been based on this hypothesis, the alternative view-that the fast force
      transients are caused by fast components of attachment and detachment--has not
      been excluded definitively. Here we show that measurements of the axial motions
      of the myosin heads at angstrom resolution by a new X-ray interference technique
      rule out the rapid attachment/detachment hypothesis, and provide compelling
      support for the working stroke model of force generation.

PMID- 11832950
TI  - RanGAP mediates GTP hydrolysis without an arginine finger.
AB  - GTPase-activating proteins (GAPs) increase the rate of GTP hydrolysis on guanine
      nucleotide-binding proteins by many orders of magnitude. Studies with Ras and Rho
      have elucidated the mechanism of GAP action by showing that their catalytic
      machinery is both stabilized by GAP binding and complemented by the insertion of
      a so-called 'arginine finger' into the phosphate-binding pocket. This has been
      proposed as a universal mechanism for GAP-mediated GTP hydrolysis. Ran is a
      nuclear Ras-related protein that regulates both transport between the nucleus and
      cytoplasm during interphase, and formation of the mitotic spindle and/or nuclear
      envelope in dividing cells. Ran-GTP is hydrolysed by the combined action of Ran
      binding proteins (RanBPs) and RanGAP. Here we present the three-dimensional
      structure of a Ran-RanBP1-RanGAP ternary complex in the ground state and in a
      transition-state mimic. The structure and biochemical experiments show that
      RanGAP does not act through an arginine finger, that the basic machinery for fast
      GTP hydrolysis is provided exclusively by Ran and that correct positioning of the
      catalytic glutamine is essential for catalysis.

PMID- 11832954
TI  - Malaria in 2002.
AB  - The burden of malaria is increasing, especially in sub-Saharan Africa, because of
      drug and insecticide resistance and social and environmental changes. Thus, there
      is an urgent need for vaccines, new drugs and insecticides. Parasite, mosquito
      and human genome projects are helping in the search for new control tools and
      international donors are developing new funding mechanisms that could make them
      available to poor countries. But these new tools will achieve their maximum
      impact only if additional resources are deployed to strengthen malaria research
      and control communities in countries where the new tools will be used.

PMID- 11832955
TI  - The pathogenic basis of malaria.
AB  - Malaria is today a disease of poverty and underdeveloped countries. In Africa,
      mortality remains high because there is limited access to treatment in the
      villages. We should follow in Pasteur's footsteps by using basic research to
      develop better tools for the control and cure of malaria. Insight into the
      complexity of malaria pathogenesis is vital for understanding the disease and
      will provide a major step towards controlling it. Those of us who work on
      pathogenesis must widen our approach and think in terms of new tools such as
      vaccines to reduce disease. The inability of many countries to fund expensive
      campaigns and antimalarial treatment requires these tools to be highly effective
      and affordable.

PMID- 11832956
TI  - The economic and social burden of malaria.
AB  - Where malaria prospers most, human societies have prospered least. The global
      distribution of per-capita gross domestic product shows a striking correlation
      between malaria and poverty, and malaria-endemic countries also have lower rates
      of economic growth. There are multiple channels by which malaria impedes
      development, including effects on fertility, population growth, saving and
      investment, worker productivity, absenteeism, premature mortality and medical
      costs.

PMID- 11832957
TI  - Medical need, scientific opportunity and the drive for antimalarial drugs.
AB  - Continued and sustainable improvements in antimalarial medicines through focused
      research and development are essential for the world's future ability to treat
      and control malaria. Unfortunately, malaria is a disease of poverty, and despite
      a wealth of scientific knowledge there is insufficient market incentive to
      generate the competitive, business-driven industrial antimalarial drug research
      and development that is normally needed to deliver new products. Mechanisms of
      partnering with industry have been established to overcome this obstacle and to
      open up and build on scientific opportunities for improved chemotherapy in the
      future.

PMID- 11832958
TI  - Progress and challenges for malaria vaccines.
AB  - Malaria causes much physical and economic hardship in tropical regions,
      particularly in communities where medical care is rudimentary. Should a vaccine
      be developed, it is the residents of these areas that stand to benefit the most.
      But the vaccine, which has been promised to be 'just round the corner' for many
      years, remains elusive. It is important to ask why this is so, when effective
      vaccines exist for many other infectious diseases. What are the reasons for the
      slow rate of progress, and what has been learned from the first clinical trials
      of candidate malaria vaccines? What are the remaining challenges, and what
      strategies can be pursued to address them?

PMID- 11832959
TI  - Plasmodium, human and Anopheles genomics and malaria.
AB  - The Plasmodium spp. parasites that cause malaria are transmitted to humans by
      Anopheles spp. mosquitoes. Scientists have now amassed a great body of knowledge
      about the parasite, its mosquito vector and human host. Yet this year there will
      be 300-500 million new malaria infections and 1-3 million deaths caused by the
      disease. We believe that integrated analyses of genome sequence, DNA
      polymorphisms, and messenger RNA and protein expression profiles will lead to
      greater understanding of the molecular basis of vector-human and host-parasite
      interactions and provide strategies to build upon these insights to develop
      interventions to mitigate human morbidity and mortality from malaria.

PMID- 11832960
TI  - Satellite imagery in the study and forecast of malaria.
AB  - More than 30 years ago, human beings looked back from the Moon to see the
      magnificent spectacle of Earth-rise. The technology that put us into space has
      since been used to assess the damage we are doing to our natural environment and
      is now being harnessed to monitor and predict diseases through space and time.
      Satellite sensor data promise the development of early-warning systems for
      diseases such as malaria, which kills between 1 and 2 million people each year.

PMID- 11832963
TI  - Anesthesiologists and surgeons at Mount Sinai: a partnership in excellence.
AB  - Although anesthesia was available to patients when the doors of The Jews Hospital
      opened in 1855, "professional anesthetists" were not appointed to the staff until
      1902. This article traces the history of the anesthesiology staff and department,
      and documents their accomplishments over the past century.

PMID- 11832964
TI  - The Mount Sinai Hospital's role in the development of anesthesia safety
      standards.
AB  - The Department of Anesthesiology of The Mount Sinai Hospital was closely involved
      in introducing anesthesia safety standards for anesthesia breathing systems, the
      introduction of the first disposable plastic anesthesia breathing system, the
      layout of the controls on gas machines, nontoxic airways, safe ethylene oxide
      sterilization and safe obstetrical anesthesia.

PMID- 11832965
TI  - The evolution of intraoperative transesophageal echocardiography.
AB  - In this article, the development of intraoperative transesophageal
      echocardiography (TEE) is reviewed. It took two decades to develop the present
      clinical applications of TEE. This modality will continue to serve as a monitor
      and diagnostic tool to ensure better care of patients in the operating room and
      the intensive care units.

PMID- 11832966
TI  - Neuroanesthesia at The Mount Sinai Hospital.
AB  - The practice of neuroanesthesia at the Mount Sinai Medical Center focused
      initially on clinical practice, followed by specialization. This article presents
      a brief history of the division and a description of the areas of interest,
      presentations, and publications that have originated there.

PMID- 11832967
TI  - The surgical intensive care unit of The Mount Sinai Hospital: a brief history
      focusing on contributions to academic critical care medicine and excellence in
      patient care.
AB  - The Mount Sinai Hospital Surgical Intensive Care Unit (SICU) was founded in 1969.
      Drs. William Shoemaker and Christopher Bryan-Brown were the first directors.
      Since it was founded, the SICU has been an integral part of the Mount Sinai
      Medical Center, providing a wide variety of clinical services including critical
      care, central line placement, and nutritional consultation. As one of the largest
      training programs in the United States and a frequent contributor to the medical
      literature, the SICU has also played a vital role in academic critical care
      medicine.

PMID- 11832969
TI  - Advances in labor analgesia.
AB  - Approximately two-thirds of all women in the United States receive analgesia for
      labor and delivery. The ideal labor analgesic technique would confer complete
      pain relief without side effects to either the mother or the neonate. The
      analgesic technique would not cause any lower extremity motor blockade nor
      interfere with the progress or course of labor and would be sufficiently flexible
      to produce anesthesia for forceps or cesarean deliveries. Modern obstetric
      analgesia techniques and medications come close to achieving these goals. The
      following article will review current labor analgesia techniques and medications
      used during labor and delivery.

PMID- 11832968
TI  - Anesthetic implications of myasthenia gravis.
AB  - Myasthenia gravis is a disease of great significance to the anesthesiologist,
      because it affects the neuromuscular junction. Many patients with this condition
      are treated by surgical thymectomy, using techniques developed by Mount Sinai
      physicians, including Dr. Paul Kirschner, Dr. Alan E. Kark, and the late Dr.
      Angelos E. Papatestas. The authors review the anesthetic considerations in the
      management of patients with myasthenia gravis who are undergoing thymectomy and
      other surgical procedures.

PMID- 11832970
TI  - Central neuraxial analgesia in cardiac surgery.
AB  - An ideal anesthetic for cardiac surgery should provide intraoperative
      cardiovascular stability and a stable and pain-free recovery. High-dose
      narcotics, whether given as an initial bolus or by the continuous infusion
      method, certainly have brought current practice closer to this ideal. Central
      neuraxial analgesia is an alternative to high-dose narcotics, but its use has
      long been an issue of debate and concern in cardiac surgery. The need for full
      heparinization for cardiopulmonary bypass has curtailed the use of central
      neuraxial blocks. Until fairly recently, very few centers dared to attempt this
      kind of effective analgesia in cardiac surgery. However, during the last few
      years more and more reports have been published on the efficacy and safety of
      this type of analgesia when appropriate precautions are taken. The objective of
      this report is to examine some of these issues.

PMID- 11832971
TI  - Current trends in pediatric anesthesia.
AB  - New trends in pediatric anesthesia for ambulatory surgery will be described.
      Preoperative preparation as well as care of pediatric patients requiring sedation
      outside of the operating room are emphasized.

PMID- 11832972
TI  - Complications of spinal anesthesia.
AB  - Serious neurological complications after spinal anesthesia are rare, but do
      occur. The most common are postdural puncture headache and hypotension.
      Hypotension after spinal anesthesia is a physiological consequence of sympathetic
      blockade. The diagnoses and management of these sequelae are discussed.

PMID- 11832973
TI  - Anesthetic considerations for endovascular aortic repair.
AB  - Endovascular aortic repair is a new alternative to conventional surgical
      techniques. A variety of devices available for endovascular aortic repair are
      discussed and the outcomes after repair are reviewed. Anesthetic considerations
      during endovascular repair are dictated by the device being used, as well as the
      site of device deployment. Requirements for the optimization of hemodynamic
      states during proximal graft deployment are described, as well as the available
      options for induction of ventricular asystole. Since arterial rupture is always a
      risk when using this procedure, appropriate facilities must be present for
      resuscitation. Patients undergoing repair of thoracic aortic pathology may be
      candidates for perioperative transesophageal echocardiographic monitoring. Since
      a subgroup of these patients may be at risk for postoperative paraplegia,
      aggressive spinal cord protection should be considered. Patients with large
      aneurysms may be at risk for "post-implantation syndrome," which is characterized
      by hyperpyrexia, hypotension, and coagulopathy.

PMID- 11832974
TI  - Prediction of outcome in cardiac surgery.
AB  - There has been growing interest in defining and measuring outcomes for cardiac
      surgical patients. Outcomes measures have been used in many hospitals as tools
      for measuring the quality of care, although it is difficult to infer from them
      how care might be improved. Traditionally, the major outcome endpoints used in
      cardiac surgery have been the 30-day mortality and morbidity rates. Recently,
      more innovative intermediate outcomes, including health-related quality of life,
      functional status, and patient satisfaction 6 months to one year after surgery,
      have received more attention. A significant proportion of the variance in health
      care outcomes is affected by patient-related risk factors. By using outcome
      prediction tools and making conclusions based on preoperative risk factor
      information, surgeons and anesthesiologists are able to make better decisions
      about treatment strategies. Additionally, operating room and intensive care unit
      personnel can use these data to schedule cases and allocate resources more
      efficiently. These data are also very important for hospital administrators and
      insurance providers.

PMID- 11832975
TI  - The open lung concept of alveolar recruitment can improve outcome in respiratory
      failure and ARDS.
AB  - Respiratory failure is a common finding in the ICU and in the management of
      complex cases in the operating room. Over the last ten years, it has become clear
      that modes of mechanical ventilation and lung recruitment may play a role both in
      cytokine modulation and patient outcome. Early lung recruitment and alveolar
      stabilization may play a very important role in the management of patients with
      respiratory failure and adult respiratory distress syndrome (ARDS). The open lung
      concept may be the key to decreasing mortality and morbidity in these patients.
      This technique not only improves oxygenation, but also affects surfactant
      function and cytokine modulation. The open lung concept is physiologically based
      on the Law of Laplace. Adhering to the principles of the open lung concept,
      pressure-controlled ventilation may improve patient outcome by reducing the
      extent of irreversible structural damage to the lungs caused by mechanical
      ventilation.

PMID- 11832976
TI  - Recent advances in airway management.
AB  - Airway management is a critical component of modern anesthetic care. Advances in
      airway management, as well as the recent history of airway management teaching at
      The Mount Sinai Hospital, are reviewed.

PMID- 11832977
TI  - Strategies for minimizing the use of allogeneic blood during orthopedic surgery.
AB  - Selected orthopedic surgical procedures, such as total joint arthroplasty and
      spinal instrumentation, have some of the highest perioperative transfusion rates
      of all surgical procedures. Blood transfusions carry the risk of complications,
      including the transmission of disease, immunomodulation, and hemolytic and non
      hemolytic reactions. Strategies that reduce or remove the risk of allogeneic
      transfusion include preoperative autologous donation, acute normovolemic
      hemodilution, perioperative cell salvage techniques, deliberate hypotension, and
      pharmacologic interventions. This paper will review the current status of these
      therapies in the orthopedic surgical patient.

PMID- 11832978
TI  - Latex allergy.
AB  - IgE-mediated allergy to natural rubber latex is a new health hazard about which
      information has been evolving for the past decade. This sensitivity poses a
      particular threat to children with congenital malformations or a history of
      multiple surgical interventions, and to individuals with high workplace exposure,
      such as health care workers. The only currently available treatment is complete
      avoidance of latex, which may require a change of workplace and loss of career.
      Latex allergy can lead to chronic occupational asthma, anaphylaxis, and even
      death. Preventive measures must be taken, in part because no treatment is
      available. This article provides an overview of latex allergy, and recommends
      some measures that may prevent its continuing dissemination and reduce its life
      threatening risk.

PMID- 11832979
TI  - Comparison of arterial systolic pressure variation with other clinical parameters
      to predict the response to fluid challenges during cardiac surgery.
AB  - Prophylactic optimization of stroke volume during surgery has been thought by
      some to reduce complications following surgery. Mechanical ventilation has been
      shown to induce variations in systolic systemic arterial blood pressure.
      Measuring such variations in systolic pressure (SPV) might serve as an attractive
      method for guiding fluid therapy intraoperatively. It is unknown if variations in
      systolic pressure following the rapid intravenous administration of a specific
      volume of fluid would lead to changes in pressure measurements obtained from a
      pulmonary artery with sufficient sensitivity to predict or guide the need for
      expansion of the intravascular volume to optimize stroke volume as an index of
      cardiac function. The purpose of this study was to determine if such measurements
      of changes in systolic pressures would be useful in optimizing stroke volume.
      Nineteen patients undergoing cardiac surgery were enrolled in a prospective
      cohort study. Following induction of general anesthesia, one or more 250 mL
      boluses of 6% hetastarch were administered. Stroke volume was calculated from the
      cardiac output obtained by thermodilution using a pulmonary artery catheter. If
      the patient s stroke volume increased by less than 10% as a result of a given
      fluid challenge, the patient was classified as a non-responder. However, if the
      stroke volume increased by more than 10%, the patient was classified as a
      responder. The variations in systolic pressure and echocardiographic indices were
      simultaneously measured before and after the administration of each 250 mL fluid
      bolus. Pulmonary artery occlusion pressure (PAOP) values were significantly lower
      in patients who responded to fluid boluses (p=0.0085) than in those who did not.
      Similarly SPV and SPVdown values (defined as the decrease in systolic pressure
      with ventilation) were significantly greater in the responders (p<0.05). No
      significant intergroup differences were observed in SPVup (increase in systolic
      pressure with ventilation) or echocardiographic-derived left ventricular end
      diastolic area. A PAOP value less than 10 mm Hg predicted a response (sensitivity
      68%, specificity 79%). Although significant intergroup differences in the extent
      of systolic pressure variations were observed, no appropriate threshold values
      could be determined that would accurately predict the response to a fluid bolus.
      There is a relationship between SPV and SPVdown values and intravascular volume
      status. SPV and echocardiographic-derived values did not predict the response to
      a fluid bolus as well as values obtained from the pulmonary artery catheter.

PMID- 11832980
TI  - Preemptive epidural analgesia for thoracic surgery.
AB  - The purpose of this study was to determine if preemptive epidural analgesia
      performed before thoracotomy incision and during the operation reduces
      postoperative pain. Patients in the treatment group received 8 mL of 0.25%
      bupivacaine and 2 mL of fentanyl (50 microg/mL) via the epidural route prior to
      skin incision, followed by an infusion of bupivacaine 0.1% and fentanyl 10
      microg/mL at 6 mL/hr. The control group received saline in the epidural. All
      patients in both groups were dosed with 8 mL of 0.25% bupivacaine and 2 mL of
      fentanyl 50 microg/mL via the epidural route at the time of the chest closure.
      The patients in the treatment group required less isoflurane intraoperatively and
      had lower maximum pain scores in the first 6 hours postoperatively. No
      significant differences were noted after the first 6 hours.

PMID- 11832981
TI  - Rofecoxib-associated upper gastrointestinal bleed: a case report.
AB  - To our knowledge, this is the first clinical report of a rofecoxib-associated
      upper gastrointestinal hemorrhage. We urge caution in prescribing rofecoxib to
      patients with risk factors for peptic ulcer disease and recommend limiting the
      dose to 25 mg per day for these patients.

PMID- 11832982
TI  - Cervical radicular pain caused by herpes simplex virus-type 1 infection: a case
      report.
AB  - A case of a 16-year-old with herpes simplex virus type-1 infection with radicular
      arm pain is reported. The clinical implications of the case are discussed.

PMID- 11832983
TI  - Subarachnoid hemorrhage presenting as post-dural puncture headache: a case
      report.
AB  - A case of subarachnoid hemorrhage following spinal anesthesia for prostate
      radioactive seed implantation is reported. The implications of the differential
      diagnosis of post-dural puncture headache are discussed.

PMID- 11832984
TI  - [Results of 903 settlement proceedings in internal medicine].
AB  - BACKGROUND AND OBJECTIVE: Physicians - as others in their activities - err and
      may cause injuries to patients. The case material of Schlichtungsstellen and
      Gutachterkommissionen (expert panels for extrajudicial claims resolution) may
      provide suggestions as to the nature and gravity of negligent adverse events in
      medical care. METHODS: Cases are decided by members of the panel, one physician
      and one lawyer being responsible for each case. They assess, aided by external
      expert opinion, records for evidence of negligence and, in case of negligence,
      for a causal relation to injury. Given that relation, they recommend compensation
      in favor of the patient. Data on complaints, mistakes and injuries are filed.
      RESULTS: We assumed negligence in 40 % of our 903 panel cases (most frequently
      due to mistakes in diagnosis, indication and monitoring after procedures), and
      negligent injury, resulting in recommendations for the patient in 26 %. In the
      363 cases concerning invasive procedures (diagnostic, interventional, and
      injections) mistakes of indication outnumbered those in performing the procedure.
      Negligent injuries resulted in severe lesions or even permanent disability in 111
      patients, in 30 patients in death. Even in the cases without evidence of
      negligence, many of the patients had suffered iatrogenic injuries. CONCLUSIONS:
      Physicians must make decisions about complex problems, under very difficult
      circumstances (Eddy); diagnosis is mistaken frequently, and indication also.
      According to patients' complaints and to the relevant literature, communication
      is of crucial importance regarding the doctor-patient-relationship and the
      prevention of disputes. The number of treatment-caused lesions made visible by
      claims constitutes only a fraction of the total of iatrogenic injuries actually
      suffered by patients. The analysis of adverse events in medical care should
      include system-based sources of errors and untoward outcomes.

PMID- 11832985
TI  - [Suspected acute coronary syndrome in patients without ST-elevation. Exclusion of
      infarction, early clinical estimation and non-coronary diagnoses].
AB  - BACKGROUND AND OBJECTIVE: Patients admitted to the hospital with suspected acute
      coronary syndrome (ACS) represent a collective at high risk. The NOWIS substudy
      aimed at evaluating 3 points: (1) Safe exclusion of myocardial infarction by
      history, symptoms, biochemical markers and the ECG, (2) value of the first
      diagnosis by the physician in the emergency room, and (3) prevalence and
      distribution of non-coronary leading diagnoses. PATIENTS AND METHODS: In 164
      patients admitted with suspected ACS without ST-segment elevation (73 % men,
      median age 66 years) the cardiac markers myoglobin, troponin T and CK/CK-MB were
      assessed on admission and 4 h later. In 2 of the NOWIS centers, the diagnosis on
      admission, derived from the ECG, history and clinical symptoms, was compared with
      the leading diagnosis at discharge, based on coronary angiography and, if
      negative, on additional esophago-gastroscopy. RESULTS: (1) Myoglobin was the
      biochemical marker with the highest sensitivity 4 h after admission for acute
      myocardial infarction (classic) definition by CK-MB elevation) with 90.4 %,
      followed by troponin T with 84.6 %. Four h after admission, in 15.4 % of the
      infarction patients (prevalence 31.7 %) troponin T was normal. (2) The admission
      diagnosis instable angina pectoris was confirmed in 46.7 % (57 of 122), suspected
      acute infarction in 76.2 % (32 of 42). On the other hand, 90.4 % (57 of 63) of
      the patients with instable angina as leading diagnosis at discharge were
      correctly diagnosed on admission, but only 61.5 % (32 of 42) of the patients with
      infarction. (3) At discharge, 29.9 % (49 of 164) of the patients had a non
      coronary leading diagnosis. Here, the most common were gastro-intestinal (55.1
      %), costo-vertebral (18.4 %) and broncho-pulmonary (16.3 %). CONCLUSIONS: (1)
      Troponin and myoglobin are helpful in patients without ST-segment elevation; yet,
      4 h after admission, a safe exclusion of myocardial infarction is not possible.
      (2) The clinical diagnosis on admission is important. However, it corresponds
      with the leading diagnosis at discharge, based on coronary angiography, in only
      50 to 75 %. Patients admitted with suspected ACS should be monitored for 24 h in
      the hospital (chest pain units or coronary care units). (3) Nearly one third of
      the patients initially admitted with suspected ACS show a non-coronary leading
      diagnosis, thus underlining the value of further investigations and of an
      interdisciplinary approach.

PMID- 11832986
TI  - [One catches not only mice with bacon. An atraumatic treatment for cutaneous
      myiasis].
AB  - HISTORY AND ADMISSION FINDINGS: A 37 year old patient was admitted because of
      four prurigous furunculoid swellings on his right upper knee. The patient had a
      history of traveling in Brasil for 6 weeks, returning 2 weeks before admission.
      The nodular skin lesions, 2.5 cm in diameter, had a central opening, from where
      under little pressure a seropurulent fluid discharged. In the central opening
      moving, whitish structures were visible. TREATMENT AND COURSE: A piece of raw
      bacon, serving as occlusion-material, was fixated on the affected skin for two
      hours. The larvae emerged due to oxygen deficiency. After retraction of the bacon
      it was possible to grasp the emerged end of the larvae with tweezers and pull
      them out completely. The larvae were identified as third instar of dermatobia
      hominis. CONCLUSION: Cutaneous myiasis is a worthy differential diagnosis in
      patients presenting with furunculoid skin lesions after traveling to endemic
      areas. The treatment with bacon as an occlusion-material offers an atraumatic
      alternative to surgical excision.

PMID- 11832987
TI  - [Thrombophilia--diagnostic steps and therapeutic consequences after deep vein
      thrombosis].
AB  - SUMMARY: In developed countries there is an age dependent increasing incidence of
      deep vein thrombosis. Hereditary thrombophilia is usually suspected by the
      clinical constellation and anamnestic informations. For economical reasons
      usually laboratory testing should be avoided if the results will not change
      directly the therapeutic process. But for hereditary defects consequences for the
      patient in future and for relatives should be taken into account especially as
      more selective strategies for prophylaxis and treatment have to be expected by
      increasing information in that field of research. As deficiencies of
      anticoagulant proteins (PC, PS, AT) have an impact on anticoagulant treatment,
      the indication for testing should not be held too strict. Time point for
      diagnostic procedures should be early after a thromboembolic event as negative
      results exclude hereditary defects definitely which allows the planning of the
      aimed treatment duration. After first onset of deep vein thrombosis, even in
      presence of hereditary coagulation defects the duration of anticoagulation
      usually depends on the clinical and anamnestic signs for a thrombophilic tendency
      of the individual patient. First publications suggest the need for prolonged
      anticoagulation of carriers with combined defects, showing an elevated rate of re
      thrombosis after the first thromboembolic event, when anticoagulation is stopped.
      Every ongoing anticoagulation should be checked repeatedly in the sense of a risk
      -benefit evaluation even for patients with a thrombophilic tendency and should be
      adapted to actual publications.

PMID- 11832988
TI  - [Sexuality in relation to heart disease. What effect does a dialogue between
      doctor and patient have?].

PMID- 11832989
TI  - [Herbert Plugge--forgetting medical patterns. A remembrance in the 30th year of
      his death].

PMID- 11832990
TI  - [Is laser-induced thermotherapy (LITT) advisable for neoplastic diseases?].

PMID- 11832991
TI  - [Therapeutic options for vascular ectasia of the stomach antrum (watermelon
      stomach)].

PMID- 11832992
TI  - [Urinary tract infections].

PMID- 11832993
TI  - Inhibition of oestrone sulphatase activity by tibolone and its metabolites.
AB  - Tibolone is a 19-nortestosterone derivative commonly used in hormone replacement
      therapy. Although tibolone and its 3alpha/beta-hydroxy metabolites exert
      oestrogenic effects on bone and the vasomotor system, they do not appear to
      stimulate breast tissue proliferation. It has been proposed that the lack of an
      oestrogenic effect on breast tissues may result from the inhibition of oestrone
      sulphatase (E1-STS) in this tissue by tibolone and its metabolites. In this study
      we have examined the ability of tibolone and its metabolites to inhibit E1-STS
      activity in intact breast cancer cells, its effect on E1-STS activity in
      placental microsomes and also the expression of E1-STS mRNA in more detail. As
      the major proportion of hydroxytibolone metabolites circulate in a sulphated
      form, the ability of the 3alpha-sulphate and 3alpha,17beta-disulphate metabolites
      to inhibit E1-STS activity was also examined. In MCF-7 cells, tibolone and its
      3beta-hydroxylated metabolite were relatively potent inhibitors; they inhibited
      activity by 48 % and 46 %, respectively. In these cells, the 3alpha-sulphate and
      3alpha,17beta-disulphate metabolites of tibolone inhibited E1-STS activity by 95%
      and 79% at 10 microM, respectively. No effects of tibolone or its metabolites on
      the expression of E1-STS mRNA in MCF-7 cells were detected. Using T-47D breast
      cancer cells, evidence was obtained that the sulphated metabolites of tibolone
      could continue to inhibit E1-STS activity after removal of the drugs and
      extensive washing of cells. In placental microsomes, however, the 3beta-hydroxy
      metabolite was the most potent inhibitor with an IC50 of 20.5 microM; the
      sulphated metabolites were less potent. Neither tibolone nor its metabolites had
      any inhibitory effect on the conversion of oestrone to oestradiol in breast
      cancer cells. Results from this study have confirmed that tibolone and its
      metabolites can inhibit E1-STS activity. This may explain the absence of breast
      stimulation as observed in clinical studies.

PMID- 11832994
TI  - Immunoregulation during disease progression in prediabetic NOD mice: inverse
      expression of arginase and prostaglandin H synthase 2 vs. interleukin-15.
AB  - Non-obese diabetic (NOD) mice spontaneously develop insulin dependent diabetes
      due to autoimmune destruction of beta-cells. The progression of insulitis can be
      accelerated and synchronized in the pancreas by a single injection of 250 mg/kg
      cyclophosphamide. In this study, we will report on three immune mediators that
      were not known to be expressed during insulitis until now. Early insulitis in ten
      week-old female NOD mice was associated with strong expression of prostaglandin H
      synthase 2 in the pancreas and of arginase, an antagonist enzyme of the inducible
      NO synthase. After acceleration of insulitis progression by cyclophosphamide,
      expression of the two enzymes was downregulated within 24 h. There was strong
      concomitant upregulation of IL-15 gene expression that preceded lymphocyte
      invasion of islets and a rise of IFN-gamma mRNA levels by several days. The
      comparison of individual pancreata showed that the expression of IL-12 and IL-18
      mRNA closely correlated with levels of IL-15 gene expression. We conclude that
      arginase and prostaglandin H synthase 2 expression is associated with peri
      insulitis, while IL-15 is a candidate cytokine in driving destructive insulitis,
      as it elicits Th1-cytotoxic responses in lymphoid as well as in non-lymphoid
      immune cells and is unusually resistant to downregulation by antagonistic
      cytokines. This is the first report on arginase, prostaglandin H synthase 2 and
      IL-15 expression in pancreatic lesions of prediabetic NOD mice.

PMID- 11832996
TI  - Hepatocyte growth factor in human breast milk acts as a trophic factor.
AB  - To evaluate the significance of hepatocyte growth factor (HGF) in milk in the
      perinatal period, we examined immunoreactive HGF levels and bioactivity in human
      milk. Human milk samples were obtained from women at various postpartum ages, and
      the levels of HGF were measured by ELISA. In the cross sectional study, the
      concentration of milk HGF from term deliveries showed a significant inverse
      correlation with progress of lactation, whereas in cases of preterm delivery
      concentrations, levels remained high after a long period of lactation. In the
      longitudinal analysis, the contents of HGF in colostrum, transitional, and mature
      milk from preterm deliveries were significantly be higher than those from term
      deliveries. Although mature milk from term and preterm deliveries contained
      significantly lower levels of HGF than colostrum, high levels of HGF persisted in
      mature milk from preterm deliveries. After partial purification, immunoblotting
      analysis showed the presence of both alpha- and beta-chains of HGF. HGF in milk
      stimulated proliferation of rat hepatocytes in primary culture, which was
      inhibited by supplementation with anti-HGF antibody. Thus, a high concentration
      of bioactive HGF is present in human milk in the postpartum period. Our results
      suggest that HGF in milk acts as a trophic factor for the gastrointestinal tract
      in neonates.

PMID- 11832995
TI  - Resistance of succinic acid dimethyl ester insulinotropic action to exendin (9
      39) amide.
AB  - Exendin (9-39) amide (Ex [9-39]) was recently proposed for use in the treatment
      of alimentary or reactive hypoglycaemia. It was indeed found to antagonise the
      insulinotropic action of GLP-1 in rats infused with the dimethyl ester of
      succinic acid (SAD). We have now investigated whether, under comparable
      experimental conditions, Ex (9-39) also opposes the insulin-releasing action of
      SAD itself. Since this was not the case, Ex (9-39) could be safely used to
      abolish the incretin effect of GLP-1 without interfering with the control of
      insulin secretion by circulating nutrients.

PMID- 11832997
TI  - Plasma glucose regulation and insulin secretion in hypertriglyceridemic mice.
AB  - In this study, we examined glucose homeostasis and insulin secretion in
      transgenic mice overexpressing the human apolipoprotein CIII gene (apo CIII tg).
      These mice have elevated plasma levels of triglycerides, FFA and cholesterol
      compared to control mice. The body weight, plasma glucose, and insulin levels,
      glucose disappearance rates, areas under the ipGTT curve for adult (4 - 8 mo.
      old) and aged (20 - 24 mo. old) apo CIII tg mice and the determination of insulin
      during the ipGTT were not different from those of control mice. However, an
      additional elevation of plasma FFA by treatment with heparin for 2 - 4 h impaired
      the ipGTT responses in apo CIII tg mice compared to saline-treated mice. The
      glucose disappearance rate in heparin-treated transgenic mice was slightly lower
      than in heparin-treated controls. Glucose (22.2 mmol/l) stimulated insulin
      secretion in isolated islets to the same extent in saline-treated control and apo
      CIII tg mice. In islets from heparin-treated apo CIII tg mice, the insulin
      secretion at 2.8 and 22.2 mmol glucose/l was lower than in heparin-treated
      control mice. In conclusion, hypertriglyceridemia per se or a mild elevation in
      FFA did not affect insulin secretion or insulin resistance in adult or aged apo
      CIII tg mice. Nonetheless, an additional elevation of FFA induced by heparin in
      hypertriglyceridemic mice impaired the ipGTT by reducing insulin secretion.

PMID- 11832998
TI  - Effect of short-term low-intensity exercise on insulin sensitivity, insulin
      secretion, and glucose and lipid metabolism in non-obese Japanese type 2 diabetic
      patients.
AB  - The aim of the present study was to investigate the effects of short-term
      physical exercise that did not change body mass on insulin sensitivity, insulin
      secretion, and glucose and lipid metabolism in 39 non-obese Japanese type 2
      diabetic patients. Insulin sensitivity and insulin secretion were estimated with
      homeostasis model assessment insulin resistance (HOMA-IR) and HOMA-B-cell
      function proposed by Matthews et al., respectively. All patients were
      hospitalized and were engaged in low-intensity exercise that consisted of walking
      and dumbbell exercise for successive 7 days. There were no changes in hospital
      diet and the dose of any medications used throughout the study. Fasting glucose,
      insulin, and lipids were measured before and after exercise. After exercise,
      serum triglyceride levels significantly decreased, but no significant changes
      were observed in total and HDL cholesterol concentrations. Fasting glucose,
      insulin, and HOMA-IR levels significantly decreased after exercise, but HOMA-B
      cell function did not change during the study. There was no significant
      difference between BMI levels before and after exercise. From these results, it
      can be concluded that short-term (7 days) low-intensity physical exercise
      combined with hospital diet reduces serum triglycerides, insulin resistance, and
      fasting glucose levels without affecting BMI in non-obese Japanese type 2
      diabetic patients.

PMID- 11832999
TI  - A blood pressure cut-off level identified for renal failure, but not for
      macrovascular complications in type 2 diabetes: a 10-year observation study.
AB  - AIMS: Can a cut-off blood pressure level for major complications be identified?
      METHODS: A 10 years observation study in 385 type 2 diabetic patients. RESULTS:
      158 patients were affected with myocardial infarction, stroke, renal failure or
      death, which occurred in 68, 55, 19 and 109 patients, respectively. No patient
      with a blood pressure below 140 mmHg and/or a diastolic blood pressure below 75
      mmHg developed uraemia during the observation period. No such cut-off level was
      seen for myocardial infarction, stroke or death. CONCLUSIONS: This study shows
      that there seems to be a cut-off level for blood pressure for development of
      renal failure, while no level was found for cardio- or cerebrovascular disorders.

PMID- 11833000
TI  - Induction of TSH-receptor antibodies in patients with toxic multinodular goitre
      by radioiodine treatment.
AB  - Previous studies have indicated pre-existing subclinical Graves' disease (GD) in
      many patients with the scintigraphic diagnosis of disseminated thyroid autonomy
      (DISA) or toxic multinodular goitre (TMG) type A. After radioiodine (RAI)
      treatment, an increase or the induction of TSH-receptor antibodies (TRAbs) in
      patients with GD or TMG has been repeatedly reported. In the present study, we
      investigated whether RAI could induce TRAbs in patients with TMG in whom pre
      existing GD was excluded with highly sensitive TBII and TSAB assays. Therefore,
      TRAbs, anti-thyroperoxidase antibodies (anti-TPO-Abs) and anti-thyroglobulin
      antibodies (anti-TG-Abs) were determined in 43 consecutive patients at the
      nuclear medicine outpatient clinic with the scintigraphic diagnosis of toxic
      adenoma (TA; n = 20) or TMG type A (n = 11) or type B (n = 12) before and after
      RAI treatment. After RAI therapy, we detected TRAbs in 36 % (4 of 11) of patients
      with TMG type A only, whereas TRAbs were not detectable in patients with TMG type
      B or in patients with TA. Furthermore, 3 of the 4 patients with detectable TRAbs
      after RAI showed positive anti-TPO-Abs before RAI therapy. These findings provide
      further evidence for pre-existing GD in patients with TMG type A or DISA as
      previously suggested. Therefore, patients with TMG type A and high anti-TPO-Abs
      seem to be at increased risk of developing TRAbs or side-effects such as relapse
      of hyperthyroidism or thyroid associated ophthalmopathy. These patients therefore
      require more frequent evaluation after RAI treatment.

PMID- 11833001
TI  - Long-term effects of malnutrition during lactation on the thyroid function of
      offspring.
AB  - Some studies have shown that the mother's nutritional condition may influence
      offspring's endocrine function through metabolic imprinting. Recently, we showed
      that the kind of maternal malnutrition during lactation affects adult body weight
      of the offspring and it is related to milk composition. We studied lactating rats
      fed an 8 % protein-restricted diet (PR), a control 23 % protein diet (C), and an
      energy-restricted diet group (ER). After weaning, all animals received a normal
      diet until they were 180 days of age. At this time, the animals received a single
      i. p. injection of (131)I and were sacrificed 2 h after the injection. Total
      triiodothyronine (TT3) and total thyroxin (TT4) serum concentrations were
      measured by enzyme immunoassay. The PR group had significantly a higher thyroid
      (131)I uptake, TT3 serum concentration and in TT4 serum concentration, compared
      to the controls. The ER group had only significantly higher TT3 serum
      concentration. These results showed that thyroid function regulation in adulthood
      may depend on maternal nutritional condition during lactation. Probably, PR group
      had a high thyroid function, whereas the ER group only had an increase in the
      deiodination of T4. The hyperthyroidism in the PR group could explain the low
      body weight observed in those animals.

PMID- 11833002
TI  - Effects of dose and timing of calcium supplementation on bone resorption in early
      menopausal women.
AB  - Bone resorption follows a circadian rhythm that peaks at night, reflecting the
      circadian rhythm of serum parathyroid hormone. Our previous studies in early
      postmenopausal women have established that 1000 mg of calcium given at 9 p. m.
      reduced bone resorption markers overnight, but not during the day. In contrast,
      1000 mg given as a divided dose (500 mg doses at 9 a. m. and 9 p. m. each)
      reduced bone resorption markers during the day, but not during the night. We have
      now evaluated the effect of 1500 mg of calcium given as a divided dose of 500 mg
      in the morning and 1000 mg in the evening on bone resorption. We studied 26
      healthy women (median age 56 years) whose menopause was less than five years
      before. On two days, urine was collected from 9 a. m. to 9 p. m. (day
      collection), and from 9 p. m. to 9 a. m. (night collection); a further fasting
      (spot) urine sample was obtained at 9 a. m. at the end of the night collection.
      On the second day, 500 mg of calcium in the carbonate form was taken at 9 a. m.
      (at the start of the collection) and a further 1000 mg at 9 p. m. (at the start
      of the second night collection). Calcium supplementation decreased urinary
      deoxypyridinoline (DPyr/Cr) during the day (p = 0.08) and night (p < 0.05), as
      well as urinary pyridinoline (Pyr/Cr) both by day (p < 0.05) and night (p <
      0.001). There were also decreases in urine hydroxyproline. We conclude that the
      acute administration of 500 mg of calcium in the morning and 1000 mg in the
      evening to early postmenopausal women suppresses bone resorption markers during
      both the day and night.

PMID- 11833003
TI  - Localization of a gene for peripheral arterial occlusive disease to chromosome
      1p31.
AB  - Peripheral arterial occlusive disease (PAOD) results from atherosclerosis of
      large and medium peripheral arteries, as well as the aorta, and has many risk
      factors, including smoking, diabetes, hypertension, and hyperlipidemia. PAOD
      often coexists with coronary artery disease and cerebrovascular disease. Cross
      matching a population-based list of Icelandic patients with PAOD who had
      undergone angiography and/or revascularization procedures with a genealogy
      database of the entire Icelandic nation defined 116 extended families containing
      272 patients. A genomewide scan with microsatellite markers revealed significant
      linkage to chromosome 1p31 with an allele-sharing LOD score of 3.93 (P=1.04 x 10(
      5)). We designate this locus as "PAOD1." Subtracting 35 patients with a history
      of stroke increased the LOD score to 4.93. This suggests that, although PAOD and
      other vascular diseases share risk factors, genetic factors specific to subtypes
      of vascular disease may exist.

PMID- 11833004
TI  - Localization of a susceptibility gene for common forms of stroke to 5q12.
AB  - Stroke is one of the most complex diseases, with several subtypes, as well as
      secondary risk factors, such as hypertension, hyperlipidemia, and diabetes,
      which, in turn, have genetic and environmental risk factors of their own. Here,
      we report the results of a genomewide search for susceptibility genes for the
      common forms of stroke. We cross-matched a population-based list of patients with
      stroke in Iceland with an extensive computerized genealogy database clustering
      476 patients with stroke within 179 extended pedigrees. Linkage to 5q12 was
      detected, and the LOD score at this locus meets the criteria for genomewide
      significance (multipoint allele-sharing LOD score of 4.40, P=3.9 x 10(-6)). A 20
      cM region on 5q was physically and genetically mapped to obtain accurate marker
      order and intermarker distances. This locus on 5q12, which we have designated as
      "STRK1," does not correspond to known susceptibility loci for stroke or for its
      risk factors and represents the first mapping of a locus for common stroke.

PMID- 11833005
TI  - A polymorphism in the agouti signaling protein gene is associated with human
      pigmentation.
AB  - In mice and humans, binding of alpha-melanocyte--stimulating hormone to the
      melanocyte-stimulating--hormone receptor (MSHR), the protein product of
      melanocortin-1 receptor (MC1R) gene, leads to the synthesis of eumelanin. In the
      mouse, ligation of MSHR by agouti signaling protein (ASP) results in the
      production of pheomelanin. The role of ASP in humans is unclear. We sought to
      characterize the agouti signaling protein gene (ASIP) in a group of white
      subjects, to assess whether ASIP was a determinant of human pigmentation and
      whether this gene may be associated with increased melanoma risk. We found no
      evidence of coding-region sequence variation in ASIP, but detected a g.8818A-->G
      polymorphism in the 3' untranslated region. We genotyped 746 participants in a
      study of melanoma susceptibility for g.8818A-->G, by means of polymerase chain
      reaction and restriction fragment--length polymorphism analysis. Among the 147
      healthy controls, the frequency of the G allele was.12. Carriage of the G allele
      was significantly associated with dark hair (odds ratio 1.8; 95% confidence
      interval [CI] 1.2--2.8) and brown eyes (odds ratio 1.9; 95% CI 1.3--2.8) after
      adjusting for age, gender, and disease status. ASIP g.8818A-->G was not
      associated independently with disease status. This is the first report of an
      association of ASIP with specific human pigmentation characteristics. It remains
      to be investigated whether the interaction of MC1R and ASIP can enhance
      prediction of human pigmentation and melanoma risk.

PMID- 11833007
TI  - Hepatitis C Virus prevalence among patients infected with Human Immunodeficiency
      Virus: a cross-sectional analysis of the US adult AIDS Clinical Trials Group.
AB  - Hepatitis C virus (HCV) has emerged as an important etiologic agent of liver
      injury and failure in patients infected with human immunodeficiency virus (HIV).
      The prevalence and characteristics of HCV in a representative cohort of HIV
      infected patients have not been described. Therefore, a representative sample of
      1687 HIV-infected patients was studied; a 213-sample subcohort was selected by
      use of risk-based sampling from 2 large prospective US Adult AIDS Clinical Trials
      Group clinical trials. HCV prevalence, HCV RNA level, and genotype were
      determined. The weighted overall estimate of HCV prevalence in the study cohort
      was 16.1% (95% weighted confidence interval, 14.3%-17.8%), with significant
      variability depending on risk factors and HIV RNA levels. Among patients defined
      as being "at risk", 72.7% were HCV positive, whereas, among low-risk patients,
      the positivity rate was 3.5%. Genotype 1 was found in 83.3% of infected patients.
      Median HCV RNA level was 6.08x106 IU/mL. High virus loads and genotype 1
      prevalence may be important to interferon-based antiviral response rates among
      coinfected patients.

PMID- 11833006
TI  - A variation in 3' UTR of hPTP1B increases specific gene expression and associates
      with insulin resistance.
AB  - Protein tyrosine phosphatase 1B (PTP1B) inhibits insulin signaling and, when
      overexpressed, plays a role in insulin resistance (Ahmad et al. 1997). We
      identified, in the 3' untranslated region of the PTP1B gene, a 1484insG variation
      that, in two different populations, is associated with several features of
      insulin resistance: among male individuals, higher values of the insulin
      resistance HOMA(IR) index (P=.006), serum triglycerides (P=.0002), and total/HDL
      cholesterol ratio (P=.025) and, among female individuals, higher blood pressure
      (P=.01). Similar data were also obtained in a family-based association study by
      use of sib pairs discordant for genotype (Gu et al. 2000). Subjects carrying the
      1484insG variant showed also PTP1B mRNA overexpression in skeletal muscle (6,166
      plus minus 1,879 copies/40 ng RNA vs. 2,983 plus minus 1,620; P<.01). Finally,
      PTP1B mRNA stability was significantly higher (P<.01) in human embryo kidney 293
      cells transfected with 1484insG PTP1B, as compared with those transfected with
      wild-type PTP1B. Our data indicate that the 1484insG allele causes PTP1B
      overexpression and plays a role in insulin resistance. Therefore, individuals
      carrying the 1484insG variant might particularly benefit from PTP1B inhibitors, a
      promising new tool for treatment of insulin resistance (Kennedy and Ramachandran
      2000).

PMID- 11833008
TI  - [Psychotraumatology: Recent therapy approaches].
AB  - Present-day therapy approaches in psychotraumatology center around the problem of
      effective access to specific trauma symptoms: intrusions; affective blunting and
      avoidance behaviors; hyperarousal. Taking its bearings from the German and
      American PTSD therapy guidelines, the article outlines the most important therapy
      methods and assesses them in terms of relevant quality criteria. EMDR,
      cognitive/behavioral approaches, modified psychodynamic methods and trauma
      adapted inpatient psychotherapy can be recommended as long as they are used in
      conjunction with stabilizing therapy elements. Normally, further therapeutic
      interventions are also necessary, drawing on traditional methods for integrating
      the trauma into the patient's biography.

PMID- 11833010
TI  - [Somatoform complaints in the German population].
AB  - The study presents the subjective responses of a representative sample of the
      German population (2050 subjects, aged 14 to 92 years) on the prevalence of
      somatoform complaints, using the SOMS (Screening for somatoform disorders)
      developed by Rief et al. (1997). The results show that somatoform disorders are
      widespread in the German population. The symptoms named most frequently were
      pains in the back, aching limbs, pains in the arms or legs, headaches, facial
      pains and sensations of fullness in the stomach. Women named more somatoform
      complaints than men and elderly suffered more than the young. The higher rate
      found in East Germany could be accounted for by the responses of the East German
      women. Of particular economic and political relevance is the health care
      utilization behaviour of this group of patients. High medical consultation
      frequencies and increasing drug consumption were found for a significant
      proportion of all patients with somatoform disorders. In apparent contradiction
      to these findings is the classification according to DSM-IV and ICD-10, which
      diagnose somatoform disorders in only 0.2%-0.4% of the population. Such low
      prevalence can be attributed to the restrictive diagnostic criteria applied by
      these systems which obscure the real frequency of somatoform syndromes requiring
      specific treatment.

PMID- 11833009
TI  - [Posttraumatic stress disorder and trauma memory--a psychobiological
      perspective].
AB  - We postulate that posttraumatic stress disorder is maintained by learnt cortical
      and subcortical plastic changes. Specifically, we assume that classical
      conditioning leads to an intense emotional memory of the trauma that is mainly
      implicit and related to plastic changes in subcortical structures such as the
      amygdala. At the same time an insufficient explicit trauma memory is formed that
      manifests itself in insufficient cortical processing of trauma content. This
      dissociation of implicit and explicit memory prevents the extinction of the
      emotional response to the trauma and perpetuates the disorder. First empirical
      results based on this model confirm the main hypotheses.

PMID- 11833011
TI  - [A German version of the measure of parental style (MOPS)].
AB  - The "Measure of Parental Style" (MOPS, Parker et al., 1997) represents an
      internationally accepted self-assessment instrument. A German translation of the
      questionnaire, the "Fragebogen dysfunktionaler elterlicher
      Beziehungsstile"(FDEB), is presented and its construct properties are evaluated.
      In addition, characteristic parental styles in different diagnostic groups are
      assessed. Psychometric testing was performed in a sample of 108 psychotherapeutic
      outpatients and 109 students. Parental styles of different diagnostic subgroups
      were compared to the whole sample. Using discriminant analysis the predictive
      value of parental style for psychiatric diagnoses was evaluated. The internal
      consistency of the instrument and its subscales revealed to be satisfactory. The
      three-factor solution of the English version explaining 55% of variance could be
      replicated: "Indifference", "over-control", and "abuse". Compared to students
      patients scored significantly higher on all three factors. Within different
      diagnostic groups characteristic parental styles could be identified that
      correctly described 82.2% of psychiatric diagnoses. We conclude that the German
      version of the MOPS represents a useful and reliable screening and research
      instrument for the assessment of parental styles.

PMID- 11833012
TI  - [The importance of the physician after successful artificial insemination by
      donor].
AB  - A treatment by artificial insemination by donor because of male infertility
      represents a drastic experience for the affected couples. Imaginations concerning
      the importance of the anonymous donor or the physician were already picked out as
      a central theme in the past. In some studies, for example, these imaginations
      were thought to have an adverse effect on the satisfaction in the partnership as
      well as for the development of the child. Aim of the examination on hand was the
      current meaning of the treating physician six years after treatment and his
      position in the self-system of the couples concerned. 15 successful couples could
      be examined by Repertory Grid method. The results of this study showed, that the
      physician had no prominent meaningfulness for the couples six years after the
      therapy. In the analysis of the self-system of the couples, gender specific
      differences could be seen. In the self-system of the treated women, the physician
      had a position close to their self and their ideal-self. This position was
      influenced by the self-esteem of the women. A higher self-esteem was associated
      with a greater closeness to the physician as well as to their partner. The
      analysis of the self-esteem of the affected men showed a completely different
      pattern. The greater the self-esteem of the male patients, the greater the
      devaluation of the physician, which showed in a greater distance to their ideal
      self. The gender specific perceptions of the inseminating physician can be
      interpreted as specific adaptations to different coping requirements.

PMID- 11833013
TI  - [Psychosomatic and psychotherapeutic medicine goes DRG -Procedure-catalog OPS-301
      2.1 as a first step].
AB  - To demonstrate the repercussions for Psychosomatic and Psychotherapeutic Medicine
      of the politically motivated decision to introduce case mix funding for inpatient
      treatment in Germany. Description of the development of an appropriate code list
      of procedures for Psychosomatic and Psychotherapeutic Medicine within the DRG
      System. The code list OPS-301 which was valid in 2001 had no appropriate
      procedures for Psychosomatic and Psychotherapeutic Medicine. The scientific
      societies therefore had to develop possibilities for coding psychosomatic
      psychotherapeutic procedures in the new OPS-301 2.1 which is valid since January
      2002. This was achieved through the formulation of so-called complex codes, which
      are presented together with first coding tips. There are further tasks with risks
      and potential benefits which have to be accomplished after establishing these
      complex codes.

PMID- 11833014
TI  - The paths we chose: to succeed or not to succeed.

PMID- 11833015
TI  - Listening for footsteps.
AB  - The 2001 Coulter Lecture provides an opportunity for the author to reflect on
      personal experiences with rehabilitation and career development. Anecdotes are
      presented involving Drs. William Spencer and Howard Rusk; and the author
      acknowledges and expresses personal gratitude to the American Congress of
      Rehabilitation Medicine, and to mentors and colleagues. The importance of having
      an enriched and supportive environment in which to study, practice, and conduct
      research is emphasized. The author also comments on current issues of personal
      concern, including: reimbursement structures for rehabilitation services; the
      psychologic impact on patients and practitioners of pending cure-related
      interventions; the need for patient outcome research; the need for expanded
      models of community-based care and services; the need to promote independent
      living models rather than institutional or nursing home living models; the need
      to maintain advocacy for disability rights, including the Americans with
      Disabilities Act; and the need to be informed about and advocate for a United
      Nations Convention on the Rights of People with Disabilities.

PMID- 11833016
TI  - Weaning success among ventilator-dependent patients in a rehabilitation facility.
AB  - OBJECTIVES: To determine outcomes of difficult-to-wean, ventilator-dependent
      patients transferred from intensive care units to rehabilitation hospitals and to
      determine predictors of weaning success in such patients. DESIGN: A retrospective
      cohort study. SETTING: A rehabilitation facility. PARTICIPANTS: One hundred forty
      five difficult-to-wean patients (55.2% men; 83.4% white; mean age +/- standard
      deviation, 65.8 +/- 16.4y) transferred to a rehabilitation facility between July
      1994 and June 1996. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES:
      Demographic and clinical data, including variables identified previously as
      predictive of weaning success among highly selected populations. RESULTS:
      Patients' Gillespie categories (reason for ventilator dependency) included "other
      medical conditions" (eg, pneumonia, neurologic) in 42.1% of the cases,
      postoperative in 24.8%, previous lung disease (eg, chronic obstructive pulmonary
      disease, interstitial lung disease) in 15.2%, trauma in 11.7%, respiratory
      failure with multisystem failure in 3.4%, and uncomplicated acute lung injury
      (acute respiratory distress syndrome) in 2.8%. Of 145 patients, 50.3% were
      completely weaned, 4.8% were partially weaned, and 44.8% remained ventilator
      dependent. In a stepwise multivariable logistic regression analysis, significant
      predictors of weaning success included white race (odds ratio [OR] = 3.4), serum
      albumin level (OR = 2.1g/dL), and blood urea nitrogen (BUN) level (OR =
      .97mg/dL); in addition, compared with postoperative patients, patients with
      "other medical conditions" (OR = .15) or previous lung disease (OR = .08) were
      less likely to be weaned (area under receiver operating characteristic curve =
      .76). Among 31 long-term survivors who were interviewed at least 6 months after
      discharge from the rehabilitation facility, 58.1% rated their health-related
      quality of life as good or better. CONCLUSIONS: Half of the patients admitted to
      a rehabilitation facility were weaned from their ventilators. Predictors of
      weaning success included race, BUN level, albumin level, and reason for
      ventilator dependency.

PMID- 11833017
TI  - An investigation of factors predictive of independence in transfers and
      ambulation after hip fracture.
AB  - OBJECTIVES: To compare the predictive value of measurements of mobility on the
      second day postsurgery with previously established outcome predictors after hip
      fracture and to establish a statistical model for the prediction of independence
      in transfers and ambulation. DESIGN: Prospective, validation cohort study.
      SETTING: Primary care center. PATIENTS: Two samples of 50 patients admitted with
      primary diagnosis of hip fracture. INTERVENTIONS: Not applicable. MAIN OUTCOME
      MEASURES: Independence in transfers and ambulation within 2 weeks of surgery.
      Predictor variables considered were age, mental state, prefracture mobility, and
      4 measurements of transfers and ambulation on the second day postsurgery.
      RESULTS: In bivariate logistic regression analysis, all variables were
      significant predictors. In multiple logistic regression analysis, only distance
      walked and assistance required in transferring supine to sitting on day 2
      postsurgery were significant. The multiple logistic regression model produced
      from the analysis had an outcome classification accuracy of 88% when tested on an
      independent sample. CONCLUSIONS: Measurements of mobility on day 2 postsurgery
      are significant and reliable predictors of independence in transfers and
      ambulation. Further consideration of the variables age, mental state, and
      prefracture mobility do not appear to improve the accuracy of the prediction.

PMID- 11833018
TI  - Fall events among people with stroke living in the community: circumstances of
      falls and characteristics of fallers.
AB  - OBJECTIVES: To describe the frequency and circumstances of falls among a
      community sample of people with stroke and to compare characteristics of fallers
      and nonfallers. DESIGN: Cross-sectional, observational study. SETTING: Community.
      PARTICIPANTS: Forty-one community-dwelling people with stroke (26 men, 15 women;
      mean age, 69.7 +/- 11.6y), of which 23 had right-hemisphere infarction, 16 left
      hemisphere infarction, and 2 had a brainstem lesion. Time since onset of stroke
      ranged from 3 to 288 months (mean, 50mo). INTERVENTIONS: Not applicable. MAIN
      OUTCOME MEASURES: Standardized tests were used to measure mobility, upper limb
      function, activities of daily living (ADL ability), and mood. Information about
      fall events was collected by using a questionnaire. RESULTS: Twenty-one
      participants (50%) were classed as fallers, of whom 10 had fallen repeatedly. No
      significant differences were found between fallers and nonfallers on any of the
      measures used. However, those who had 2 or more falls (n = 10) had significantly
      reduced arm function (P = .018) and ADL ability (P = .010), compared with those
      who had not fallen or experienced near falls (n = 5). Loss of balance,
      misjudgment, and foot dragging during walking, turning, and sit to stand were
      reported by fallers as the suspected causes and activities leading to falls.
      CONCLUSIONS: The high risk of falling among people with stroke was evident in
      this community-based sample. Repeat fallers had greater mobility deficits and
      significantly reduced arm function and ADL ability than those who did not report
      any instability.

PMID- 11833020
TI  - Outcome of lower extremity malignancy survivors treated with transfemoral
      amputation.
AB  - OBJECTIVE: To determine outcomes of surviving patients who underwent transfemoral
      amputation as part of treatment for lower extremity malignancy at a mean 15 years
      postoperatively, with a minimum 2-year follow-up. DESIGN: Retrospective, case
      control. SETTING: Tertiary care university medical center. PATIENTS: Thirty-five
      of 38 consecutively admitted patients free of metastatic disease managed with
      transfemoral amputation as part of treatment of a lower extremity bone and/or
      soft tissue malignancy between 1966 and 1997 at 1 institution. The control group
      included 35 age- and gender-matched subjects recruited from the local driver's
      license office. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES:
      Musculoskeletal Function Assessment (MFA), Short Form-12 General Health Status
      Survey (SF-12), physical performance battery, cost, and demographic data.
      RESULTS: Controls showed superior scores as measured by the MFA (P < .0001), the
      physical component summary of the SF-12 (P = .0002), and the physical performance
      battery (P < .0001), but had inferior scores on the mental component summary of
      the SF-12 (P < .0001). With the numbers available, no differences were found
      between study and control subjects in terms of employment rate (P = .51),
      education level (P = .66), income level (P =.44), marital status (P = .79),
      incidence of self-reported health problems (P = .14), and alcohol (P =.42) and
      tobacco (P = .82) use. Ten patients were included in the cost analysis; the mean
      cost to obtain and maintain a lower extremity prosthesis was $4225 per year
      (range, 623 dollars-8517 dollars). CONCLUSIONS: Although the decrease in physical
      performance was anticipated in the study group, the group differed very little
      from the control population in terms of employment, education level, income,
      marital and home status, incidence of self-reported health problems, incidence of
      self-reported depression, and alcohol and tobacco use. Also, the long-term cost
      of maintaining a lower extremity prosthesis is noted.

PMID- 11833019
TI  - Noise-enhanced vibrotactile sensitivity in older adults, patients with stroke,
      and patients with diabetic neuropathy.
AB  - OBJECTIVE: To test the hypothesis that vibrotactile detection thresholds in older
      adults, patients with stroke, and patients with diabetic neuropathy can be
      significantly reduced with the introduction of mechanical noise. DESIGN: A
      randomized controlled study. SETTING: A university research laboratory.
      PARTICIPANTS: Twelve healthy elderly subjects (age range, 67-85y), 5 patients
      with stroke (age range, 24-64y), and 8 patients with diabetic neuropathy (age
      range, 53-77y). INTERVENTIONS: Each subject's detection thresholds (ie, minimum
      level of stimulus to be detected) for a vibrotactile stimulus without and with
      mechanical noise (ie, random vibration with a small intensity) were determined by
      using a 4-, 2-, and 1-stepping algorithm. The stimuli were applied to the
      fingertip and/or to the first metatarsal of the foot. MAIN OUTCOME MEASURE:
      Detection threshold for a vibrotactile stimulus. RESULTS: The detection threshold
      at the fingertip for the vibration stimulus with mechanical noise was
      significantly lower than that without mechanical noise for all 12 elderly
      subjects, for 4 of the 5 patients with stroke, and all 8 patients with diabetic
      neuropathy. For the 8 patients with diabetes, mechanical noise also significantly
      reduced the vibrotactile detection threshold at the foot. CONCLUSIONS: Reduced
      vibrotactile sensitivity in older adults, patients with stroke, and patients with
      diabetic neuropathy can be significantly improved with input mechanical noise.
      Noise-based techniques and devices may prove useful in overcoming age- and
      disease-related losses in sensorimotor function.

PMID- 11833021
TI  - Early cognitive status and productivity outcome after traumatic brain injury:
      findings from the TBI model systems.
AB  - OBJECTIVE: To evaluate the contribution of early cognitive assessment to the
      prediction of productivity outcome after traumatic brain injury (TBI) adjusted
      for severity of injury, demographic factors, and preinjury employment status.
      DESIGN: Inception cohort. SETTING: Six inpatient brain injury rehabilitation
      programs. PARTICIPANTS: A total of 388 adults with TBI whose posttraumatic
      amnesia (PTA) resolved before discharge from inpatient rehabilitation.
      INTERVENTIONS: Administered neuropsychologic tests during inpatient stay on
      emergence from PTA. Follow-up interview and evaluation. Predictor measures also
      determined. MAIN OUTCOME MEASURE: Productivity status at follow-up 12 months
      postinjury. RESULTS: Multiple logistic regression analysis revealed that
      preinjury productivity status, duration of PTA, education level, and early
      cognitive status each made significant, independent contributions to the
      prediction of productivity status at follow-up. When adjusted for all other
      predictors, persons scoring at the 75th percentile on early cognitive status
      (less impaired) had 1.61 times greater odds (95% confidence interval [CI], 1.07
      2.41) of being productive follow-up than those scoring at the 25th percentile
      (more impaired). Without adjustment, persons scoring at the 75th percentile had
      2.46 times greater odds (95% CI, 1.77-3.43) of being productive at follow-up.
      CONCLUSIONS: Findings support the utility of early cognitive assessment by using
      neuropsychologic tests. In addition to other benefits, early cognitive assessment
      makes an independent contribution to prediction of late outcome. Findings support
      the clinical practice of performing initial neuropsychologic evaluations after
      resolution of PTA.

PMID- 11833022
TI  - The physical activity scale for individuals with physical disabilities:
      development and evaluation.
AB  - OBJECTIVE: To evaluate the construct validity of a new 13-item physical activity
      survey designed to assess physical activity in individuals with physical
      disabilities. DESIGN: Mail survey requesting information on physical activity,
      basic demographic characteristics, self-rated health, and self-rated physical
      activity. SETTING: In February 2000, surveys were sent to 1176 individuals who
      had used rehabilitative services at a major midwestern university between 1950
      and 1999. PARTICIPANTS: Two hundred twenty-seven men and 145 women with
      disabilities responded to the mail survey (80%, spinal cord or other locomotor
      injuries; 13%, visual and auditory injuries; 7%, other; 92%, white; mean age +/-
      standard deviation, 49.8 +/- 12.9y; mean length of disability, 36.9 +/- 14.9y).
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Physical activity was
      assessed with the Physical Activity Scale for Individuals with Physical
      Disabilities (PASIPD). The PASIPD requests the number of days a week and hours
      daily (categories) of participation in recreational, household, and occupational
      activities over the past 7 days. Total scores were calculated as the average
      hours daily times a metabolic equivalent value and summed over items. RESULTS:
      Pearson correlations between each survey item and the total PASIPD score were all
      statistically significant (P < .05) and >or= .20 (range, .20- .67). Factor
      analysis with principal component extraction and varimax orthogonal rotations
      revealed 5 latent factors (eigenvalues >or= 1, factor loadings >or= .40): home
      repair and lawn and garden, housework, vigorous sport and recreation, light sport
      and recreation, and occupation and transportation. These 5 factors accounted for
      63% of the total variance. Cronbach alpha coefficients ranged from.37 to.65,
      indicating low-to-moderate internal consistency within factors. Those who
      reported being "active/highly active" had higher total and subcategory scores
      compared with those "not active at all." Those in "excellent" health had higher
      total, vigorous sport and recreation, and occupation and transportation
      subcategory scores compared with those who rated their health "fair/poor" (all P
      < .05). CONCLUSION: These results provide preliminary support for the construct
      validity of the PASIPD. Additional validation studies using an external criterion
      and in more generalizable samples are warranted.

PMID- 11833023
TI  - A comparison of 2 circuit exercise training techniques for eliciting matched
      metabolic responses in persons with paraplegia.
AB  - OBJECTIVE: To test whether acute metabolic (VO(2)), chronotropic (heart rate),
      and perceptual (rating of perceived exertion; RPE) responses to exercise by
      persons with paraplegia differ when the exercise is on a multistation isoinertial
      exercise system (MultiGym) or on a customized system of Thera-Band resistance
      bands (ElasticGym). DESIGN: Within-subjects comparison of 2 treatments. SETTING:
      Academic medical center. PARTICIPANTS: Sixteen men and 1 woman with complete
      paraplegia (T4-L1), as defined by the American Spinal Injury Association.
      INTERVENTIONS: A circuit resistance training (CRT) program for persons with
      paraplegia was adapted to both a MultiGym and a customized ElasticGym. Exercises
      used for training and testing used 6 resistance maneuvers at 50% of the 1
      repetition maximum (1-RM), with interposed rapid arm spinning. Subjects were
      habituated to both conditions for 2 weeks before testing on randomized
      nonconsecutive days. MAIN OUTCOME MEASURES: VO(2) (L/min) was measured by
      portable spirometry, heart rate (beats/min) by a chest strap monitor, and RPE by
      the Borg Scale of Perceived Exertion (6-20). RESULTS: No significant effects of
      test condition on average VO(2) or heart rate were observed, with differences
      between conditions reflecting only .08L/min and 6.4 beats/min, respectively.
      Average RPE was significantly higher in testing under the ElasticGym condition (P
      < .05). CONCLUSIONS: CRT on a customized ElasticGym system elicited acute
      metabolic and chronotropic responses that did not differ from responses to
      exercise on a MultiGym, though RPE was greater with the ElasticGym.

PMID- 11833024
TI  - Effect of strenuous arm crank exercise on platelet function in patients with
      spinal cord injury.
AB  - OBJECTIVE: To investigate the effects of arm crank exercise on various platelet
      functions and prostacyclin in individuals with spinal cord injury (SCI). DESIGN:
      Case-control study. SETTING: Research project at a hospital-based exercise
      physiology laboratory. PARTICIPANTS: Seven men (with lesions at levels T11, n =
      1; T12, n = 2; L1, n = 2; L2, n = 2) and 3 women (T12, n = 1; L1, n = 2) in the
      SCI group had SCI for at least 6 weeks. Ten age- and gender-matched healthy
      people who had not engaged in any regular physical activity for at least 1 year
      were selected as the control group. INTERVENTION: All subjects exercised
      strenuously by using an arm crank engometer. MAIN OUTCOME MEASURE: Platelet
      adhesiveness on fibrinogen-coated surface and epinephrine-induced aggregation in
      vitro, plasma soluble P-selectin (sP-selectin), and urinary 6-keto-prostaglandin
      F(1alpha) (6-keto PGF(1alpha)) levels. RESULTS: The SCI group had higher platelet
      adhesiveness and aggregability and plasma sP-selectin level, but lower urinary 6
      keto PGF(1alpha) level than the control group. Platelet adhesiveness and
      aggregability were enhanced by strenuous arm exercise in all subjects, but only
      in the SCI group was sP-selectin level increased by exercise. Strenuous exercise
      raised the levels of 6-keto PGF(1alpha) in control group subjects, but not in
      subjects with SCI. CONCLUSIONS: Individuals with SCI had more extensive basal and
      exercise-induced platelet activation and sP-selectin release than people without
      SCI. Moreover, strenuous arm exercise, which enhanced the release of prostacyclin
      in healthy subjects, failed to do so in those with SCI.

PMID- 11833025
TI  - Motor performance deteriorates with simultaneously performed cognitive tasks in
      geriatric patients.
AB  - OBJECTIVE: To investigate whether simultaneous cognitive tasks influence maximal
      motor performance in frail geriatric patients with a history of injurious falls
      and different levels of cognitive function. DESIGN: Experimental 3-group design.
      SETTING: Geriatric rehabilitation hospital. PARTICIPANTS: Twenty-two healthy,
      young adults (mean age +/- standard deviation, 27.7 +/- 9y) and 23 geriatric
      patients (mean age, 80.9 +/- 5.4y) with a history of injurious falls with (Mini
      Mental State Examination [MMSE] score, 20.5 +/- 1.6) and without (MMSE score,
      28.1 +/- 1.2) cognitive impairment. INTERVENTIONS: Not applicable. MAIN OUTCOME
      MEASURE: Motor performance: peak and integral of maximal isometric strength of
      leg extensors. Cognition: semiautomated calculation steps (serial 2 forward) and
      nonautomated calculation steps derived from the MMSE (serial 7 retro). Motor and
      cognitive performances were examined as single and dual tasks. RESULTS: In frail
      geriatric patients, especially in patients with cognitive impairment, maximal
      motor performance decreased significantly during all dual tasks. Cognitive
      performance was reduced, depending on the task and group. CONCLUSION: In frail or
      cognitively impaired geriatric patients, additional tasks can substantially
      decrease maximal motor performance. Insufficient resources on dual tasking may
      thus be a link in connecting the high incidence of falls with frailty and
      cognitive impairment in geriatric patients with a history of injurious falls.

PMID- 11833026
TI  - Effects of isokinetic ankle fatigue on the maintenance of balance and postural
      limits.
AB  - OBJECTIVE: To quantify changes in balance parameters and ranges of postural
      control at the ankle after isokinetic fatigue. DESIGN: Before-after trials, with
      a 5 x 6 repeated-measures design. SETTING: General community. PARTICIPANTS:
      Twenty-four men (age, 24.9 +/- 3.92y; height, 177.79 +/- 6.36cm; weight, 80.78 +/
      13.22kg) without ankle trauma within 2 years. INTERVENTIONS: Fatigue of the
      plantarflexors and dorsiflexors was induced by isokinetic contractions. Balance
      was assessed by using a unilateral test (15-s quiet stance, 10-s lean test) on a
      force platform immediately before and at 0 (T0), 10 (T10), 20 (T20), and 30 (T30)
      minutes postfatigue. MAIN OUTCOME MEASURE: Mediolateral (ML) and fore-aft (FA)
      sway as well as ML and FA displacement were analyzed by analysis of variance with
      repeated measures for time (alpha =.05). RESULTS: In quiet stance, ML sway was
      greater at T0, whereas total sway increased at all time points postfatigue (P <
      .05). For the lean test, FA sway increased at T0 and T10, and total sway
      increased at all time points (P < .05). Both ML and FA displacement significantly
      differed at T0 (P < .05). All sway parameters returned to baseline within 20
      minutes. CONCLUSIONS: Isokinetic fatigue of ankle plantarflexors and dorsiflexors
      significantly influences sway parameters and ranges of postural control in
      healthy young men. These perturbations are transient, and recovery occurs within
      20 minutes.

PMID- 11833027
TI  - Physical disability and the experience of chronic pain.
AB  - OBJECTIVES: To obtain an insider's view about disability-related pain to help
      rehabilitation clinicians understand the experience and to show how people with
      disability manage daily living and encounters with other people. DESIGN:
      Qualitative methods by using open-ended interviews and thematic analysis.
      SETTING: Rehabilitation research program. PARTICIPANTS: Nine adults with chronic
      physical disability and pain were recruited from study groups. The 9 included
      people with spinal cord injury, acquired amputation, or cerebral palsy.
      INTERVENTION: Interview protocol. MAIN OUTCOME MEASURE: Phenomenologic analysis
      of interviews based on codewords derived from interview topics and themes.
      RESULTS: Study participants described pain as a part of daily living that
      influenced many lifestyle decisions. They characterized pain as plural, meaning
      that it has multiple locations, distinctive descriptions, and different
      implications. They also were concerned about pain being a mystery, having unclear
      causes and consequences. Typically they described pain as a personal venture,
      with little or dissatisfying communication about pain with family, friends, or
      health care providers. CONCLUSIONS: Understanding pain associated with physical
      disability can help guide rehabilitation practitioners in their pain assessments,
      interventions, and related research. Our findings suggest that some people with
      disability-related pain may benefit from reassurance and specific planning for
      expected and unexpected pain episodes.

PMID- 11833028
TI  - The reliability and validity of pain interference measures in persons with
      cerebral palsy.
AB  - OBJECTIVE: To evaluate the reliability and validity of 2 measures of pain
      interference in persons with cerebral palsy (CP). DESIGN: Standardized interviews
      to assess pain and impact of pain on activities. SETTING: University medical
      center. PARTICIPANTS: Fifty adults with CP. INTERVENTIONS: Patients asked to rate
      pain's intensity, interference with general activities, and depression levels.
      MAIN OUTCOME MEASURES: Pain interference scales: Chronic Pain Grade (CPG) and
      Brief Pain Inventory (BPI); rating of disability: Craig Handicap Assessment and
      Reporting Technique (CHART); rating of depression: Center for Epidemiologic
      Studies Depression (CES-D) Scale. RESULTS: Mean interference of pain on 3 CPG
      items (pain interference with daily activities, social activities, work) were
      1.74 +/- 2.45, 1.06 +/- 2.05, and.89 +/- 1.84 (out of 10), respectively. Mean
      interference on 10 modified BPI interference items ranged from 2.28 +/- 3.01 to
      3.67 +/- 3.15 (out of 10). The composite CPG interference score did not correlate
      significantly with pain intensity. However, the composite BPI interference score
      did correlate significantly with pain intensity (r = .66, P < .01). There was no
      significant association shown between average pain and the CHART score (r = -.21,
      NS). Pain showed a significant association with CES-D score (r = .45, P < .05).
      Internal consistency of the 3 CPG items was inadequately low (Cronbach alpha =
      .59), whereas that of the 10 BPI items was excellent (.89). CONCLUSIONS: The pain
      interference items of the BPI serve as a reliable and valid measure of pain's
      impact on persons with CP-related pain.

PMID- 11833029
TI  - Immediate and long-term effects of ankle-foot orthosis on muscle activity during
      walking: a randomized study of patients with unilateral foot drop.
AB  - OBJECTIVES: To determine (1) whether use of an ankle-foot orthosis (AFO) by
      patients with ankle dorsiflexor paresis leads to decreased muscle activity,
      immediately or 6 weeks after AFO use, and (2) whether this decrease (if present)
      differs between healthy and paretic subjects. DESIGN: Cross-sectional and
      longitudinal randomized case-control study. SETTING: Rehabilitation research
      center in the Netherlands. PARTICIPANTS: Fourteen healthy persons and 29 patients
      with foot drop. INTERVENTIONS: Muscle activity was measured by surface
      electromyography. Electromyographic reproducibility was tested in 14 healthy
      volunteers walking with and without AFO. Acute changes in muscle activity from
      AFO use were compared between the 14 healthy persons and the 29 patients with
      foot drop. Adaptation effects of AFO use after 6 weeks were studied in 29
      patients, randomly chosen 16 of whom had started using an AFO at the first
      measurement. MAIN OUTCOME MEASURES: Amount of change in mean rectified
      electromyographic activity (delta value) between walking with and without AFO.
      Follow-up measurements were conducted after 3 and 6 weeks. RESULTS: Correlation
      coefficients, reflecting within-subject reproducibility, varied between.68 and.96
      (mean,.86). In patients and healthy subjects, tibialis anterior muscle activity
      decreased by 7% and 20% (P = .01, P = .04), respectively, when using an AFO. In
      patients, this decrease was measured in the overall activity during the gait
      cycle; in healthy subjects, it was measured in the first 15% of the gait cycle.
      Overall electromyographic activity did not change during 6 weeks; delta values
      per muscle did not change during follow-up in the AFO group. CONCLUSION: AFO use
      immediately reduced muscle activity of the ankle dorsiflexors. However, using an
      AFO for 6 weeks did not lead to a generally lower electromyographic activity
      level nor did the amount of activity reduction accumulate in comparison with
      patients who did not use an AFO. It is, therefore, safe to use an AFO, even with
      recently paretic patients.

PMID- 11833030
TI  - Patient preference and gait efficiency in a geriatric population with
      transfemoral amputation using a free-swinging versus a locked prosthetic knee
      joint.
AB  - OBJECTIVE: To investigate patient preference, walking speed, and prosthetic use
      in a geriatric population with transfemoral amputation using a free-swinging
      prosthetic knee or a locked knee joint. DESIGN: Before-after trial. SETTING:
      Ambulatory patients at an amputee rehabilitation facility. PARTICIPANTS: A
      convenience sample of 14 geriatric individuals with a unilateral dysvascular
      transfemoral amputation (age range, 61-80y), who were using a prosthesis with a
      free-swinging knee in the community, 3 months after discharge from an amputee
      rehabilitation program. INTERVENTION: Change from a free-swinging knee to a
      locked knee. MAIN OUTCOME MEASURES: Patient preference, distance walked in 2
      minutes, and prosthetic use as measured by the Houghton Scale. RESULTS: Eleven of
      14 participants preferred the locked knee. Irrespective of preference, the mean 2
      minute walk distance was 44.9 +/- 28.9m with the free-swinging knee and 54.4 +/-
      35m with the locked knee (P = .001). Prosthetic use was greater with the locked
      knee (7.8 +/- 2.2) than with the free-swinging knee (6.6 +/- 2.5) (P = .01).
      CONCLUSIONS: Most geriatric participants with transfemoral amputation preferred
      locked knees and walked faster and used their prostheses more when using a locked
      knee prosthesis.

PMID- 11833031
TI  - Driving characteristics of electric-powered wheelchair users: how far, fast, and
      often do people drive?
AB  - OBJECTIVES: To determine the driving characteristics of electric-powered
      wheelchair users during unrestricted community activities and to compare the
      activity levels among an active group and a group of regular users. DESIGN:
      Multisite engineering evaluation of electric-powered wheelchair driving activity
      during unrestricted community mobility. SETTING: Data were collected in the
      communities of Pittsburgh, PA, and the National Veterans Wheelchair Games (NVWG)
      in San Antonio, TX. PARTICIPANTS: Seventeen people participated, all of whom used
      electric-powered wheelchairs as their primary means of mobility. INTERVENTION:
      Each subject was asked standarized questions about self and wheelchair use. Data
      logger and sensor installed on wheelchair. Data downloaded from logger. MAIN
      OUTCOME MEASURES: Speed, distance traveled, and the time that each subject's
      personal wheelchair was being driven were recorded for 24hr/d over approximately
      5 days for each subject by using a custom-built data logger. RESULTS: The NVWG
      group traveled faster than the Pittsburgh group, but this difference was only
      statistically significant on the first day. The NVWG group was more likely to
      travel longer than the Pittsburgh group with significant differences seen in day
      4 (P = .03) and day 5 (P = .05). Total distance traveled during the 5-day period
      and average distance traveled per day were also significantly different between
      the groups (P = .02 for both 5-day distance and daily distance), with the NVWG
      group traveling longer (17,164 +/- 8708m) when compared with the Pittsburgh group
      (8335 +/- 7074m) over the 5-day period. Both distance traveled and speed
      increased during afternoon and evening hours. The maximum distance traveled by
      any subject for each hour across the 2 groups was used to create the theoretic
      maximum distance day, which resulted in 7970m of driving. CONCLUSION: Drivers of
      electric-powered wheelchairs are most active during the afternoon and evening
      hours. Over the 5-day period of this study, there was little variation in the
      speed or distance driven per day. The subjects participating in the NVWG were
      more active than their counterparts during a typical week at home. The maximum
      theoretic distance that a wheelchair user in our group would travel is less than
      8km. The range of current electric-powered wheelchairs appears adequate, if not
      generous, for the subjects in our study.

PMID- 11833032
TI  - Treatments of unilateral neglect: a review.
AB  - OBJECTIVES: To review the existing literature on treatments of unilateral
      neglect, to synthesize findings, and to offer recommendations for future studies.
      DATA SOURCES: Computerized databases including MEDLINE and PsychINFO. STUDY
      SELECTION: All studies investigating treatment(s) of unilateral neglect. DATA
      EXTRACTION: Authors reviewed design and other methodologic issues. DATA
      SYNTHESIS: Unilateral neglect is a common consequence of right-hemisphere stroke.
      It is well recognized that the disorder is heterogeneous and has numerous
      subtypes. There have been numerous studies showing that arousal, hemispheric
      activation, and spatial attention treatments may all improve neglect, at least
      transiently. Despite these promising outcomes, little consensus exists as to
      whether 1 treatment is more efficacious than others, in part because cross-study
      differences in methodology render meta-analyses difficult, and in part because
      many studies fail to document duration of treatment effects or generalization to
      daily activities. One possibility is that these varied and diverse treatments may
      all be effective, reflecting redundancy in neural circuits devoted to attention
      and action in space, and consequent flexibility of the spatial processing system.
      It remains possible, however, that different subtypes of neglect may respond
      differentially to treatment of various sorts. Most existing studies of neglect
      have relied on very small populations of neglect patients, whose neglect is
      characterized only generally. CONCLUSION: Methodologic shortcomings hinder
      assessment of the efficacy of various types of neglect treatment. In the future,
      these shortcomings could be addressed with larger studies of well-characterized
      patients that evaluate duration of treatment effects and include functional
      measures. In addition, the role of overarching variables, such as reduced
      arousal, requires consideration. The ultimate goal of these studies might be the
      development of triaging strategies wherein neglect patients are assigned to
      treatments of most likely benefit on the basis of neuroanatomic and behavioral
      profiles.

PMID- 11833033
TI  - Hypoglossal nerve palsy from cervical spine involvement in rheumatoid arthritis:
      3 case reports.
AB  - Rheumatoid arthritis (RA) involvement of the cervical spine is a well-known but
      perhaps underappreciated phenomenon. Neurologic complications of this involvement
      include pain, myelopathy, and cranial nerve (CN) palsies. However, hypoglossal
      nerve palsy (CN XII) is rarely diagnosed. Mechanical nerve injury, either from
      vertical odontoid subluxation or pannus formation, is the suspected mechanism. We
      present 2 cases of hypoglossal nerve palsy attributed to cervical spine
      involvement of RA and 1 case of postoperative tongue weakness after cervical
      fusion in a patient with long-standing RA. These cases show a potentially
      devastating complication of RA that may be underdiagnosed. Therapy involving the
      cervical spine must be prescribed with caution in this patient population.

PMID- 11833034
TI  - Self-controlled dorsal penile nerve stimulation to inhibit bladder hyperreflexia
      in incomplete spinal cord injury: a case report.
AB  - Intermittent catheterization is not always successful in achieving continence in
      spinal cord injury (SCI) and often requires adjunctive methods. Electric
      stimulation of sacral afferent nerves reduces hyperactivity of the bladder. This
      report describes application of self-controlled dorsal penile nerve stimulation
      for bladder hyperreflexia in incomplete SCI. The patient was a 33-year-old man
      with C6 incomplete quadriplegia who managed his bladder with intermittent self
      catheterization and medication. Despite this, he continued to have reflex bladder
      contractions that he could feel but could not catheterize himself in time to
      prevent incontinence. We performed cystometry with dorsal penile nerve
      stimulation and analyzed data of home use of stimulation. During cystometry, the
      suppressive effect of electric stimulation on hyperreflexic contractions was
      reliable and reproducible. The patient could start stimulation on sensing bladder
      contraction, and the suppression of reflex contraction lasted several minutes
      after stopping brief stimulation. When using stimulation at home, the rate of
      leakage between catheterization decreased, and catheterized volume increased
      significantly.

PMID- 11833035
TI  - Neurologic complications of sit-ups associated with the Valsalva maneuver: 2 case
      reports.
AB  - We present 2 cases of potentially catastrophic neurologic consequences occurring
      in healthy individuals engaged in sit-up exercises. Two young healthy men were
      engaged in sit-ups when one developed a stroke and the other developed a spinal
      epidural hematoma. The Valsalva maneuver involved in the sit-up exercise can
      produce supraphysiologic increases in blood pressure, which can lead to vascular
      injury and serious neurologic consequences. Proper breathing should be encouraged
      and patients with known predisposing factors should avoid such exercises. Prompt
      recognition of neurologic signs and symptoms during exercise can be life saving.
      This is the first report of the neurologic complications of sit-ups.

PMID- 11833036
TI  - Persistent paraplegia after an aqueous 7.5% phenol solution to the anterior motor
      root for intercostal neurolysis: a case report.
AB  - A 55-year-old white man with severe scoliosis and chest deformity was scheduled
      for an intercostal neurolysis for pain relief with 7.5% aqueous phenol solution.
      A 20 G needle was inserted 3 to 4cm lateral to the midline of the spine under the
      10th right rib. After negative aspiration for blood and alcohol, 6mL of a 7.5%
      aqueous phenol solution was injected. Within a minute after the injection, the
      patient felt a warm sensation in his right leg, followed by loss of leg motor and
      sensory function on both sides. A lumbar puncture done 3.5 hours after the block
      showed a phenol concentration of 87.5 microg/mL. The most likely explanation is a
      diffusion of the phenol through the intervertebral foraminae reaching the spinal
      space and therefore damaging the motor and sensory roots. This case highlights
      the danger associated with phenol application in the vicinity of the spinal cord.

PMID- 11833037
TI  - Modified constraint-induced therapy in subacute stroke: a case report.
AB  - OBJECTIVE: To determine the efficacy of a modified constraint-induced therapy
      (CIT) protocol administered to a patient with subacute stroke. DESIGN: Multiple
      baseline, before-after trial. SETTING: Subacute outpatient clinic. PATIENT: A 68
      year-old woman who had a left anterior cerebral artery infarct 5 months before
      study entry and who exhibited learned nonuse of the affected upper limb.
      INTERVENTION: Thirty minutes of structured physical therapy and 30 minutes of
      occupational therapy 3 times a week for 10 weeks, each session emphasizing
      affected arm use. During the same period, her unaffected arm and hand were
      restrained 5d/wk during 5 hours initially identified as a time of frequent use.
      MAIN OUTCOME MEASURES: The Fugl-Meyer Assessment of Motor Recovery (FMA), Action
      Research Arm Test (ARA), Wolf Motor Function Test (WMFT), and Motor Activity Log
      (MAL). RESULTS: The patient exhibited substantial improvements on the FMA and
      ARA. She also improved on the WMFT in her ability to perform tasks and in the
      time taken to complete the tasks. Amount and quality of arm use also improved, as
      measured by the MAL. CONCLUSIONS: Modified CIT may be an efficacious method of
      improving function and use of the affected arms of patients with learned nonuse.

PMID- 11833038
TI  - Estrogen treatment and body fat distribution are involved in corticotropin and
      cortisol response to corticotropin-releasing hormone in postmenopausal women.
AB  - To assess the effect of transdermal estrogen substitution on the hypothalamic
      pituitary-adrenal (HPA) axis responsiveness/sensitivity and the impact of the
      antrophometric characteristics on these parameters, 20 postmenopausal women
      seeking treatment for the relief of postemenopausal symptoms were studied. They
      received transdermal 50 microg/d estradiol for 12 weeks (estrogen replacement
      therapy [ERT]). Patients were classified as low waist-to-hip ratio (WHR)
      (peripheral fat distribution women; n = 12) and high WHR (central fat
      distribution women; n = 8) according to the cut-off value of 0.85. Plasma hormone
      and lipid concentration were assessed at baseline and after 12 weeks of
      treatment. Results were compared with a group of 8 placebo-treated patients who
      served as controls. Corticotropin (ACTH) and cortisol (F) were expressed as
      fasting values, area under the curve (AUC), and time course over 90 minutes after
      corticotropin-releasing hormone (CRH) intravenous (IV) bolus (1 microg/kg body
      weight [BW]). Adrenal sensitivity to CRH stimulus was expressed as time course
      over 90 minutes and AUC of the F/ACTH molar ratio. The plasma F levels in
      response to ACTH stimulation did not change after ERT; however, a highly
      significant improvement of adrenal sensitivity was observed (P <.01). In fact,
      estrogen treatment significantly decreased the amount of ACTH produced after CRH
      stimulation, both as absolute time course and AUC (P <.01). No significant change
      was observed in controls. Considering body fat distribution, the high WHR group
      showed higher ACTH (P <.01), lower F/ACTH values, and superimposable F plasma
      values compared with the low WHR group. Estrogen treatment induced a significant
      ACTH reduction after CRH (P <.01) only in the high WHR group, whereas cortisol
      response was similar in both groups both before and after treatment. A
      significant negative correlation was found between WHR and adrenal sensitivity
      before treatment. ERT significantly improved adrenal sensitivity only in the low
      WHR group (P <.01). These data suggest that different mechanisms can prevail in
      the control of the HPA axis in menopause. Estrogens could exert different effects
      on the hypothalamic-pituitary axis, as well as on adrenal function, and these
      changes seem to be partially dependent on the pattern of body fat distribution.

PMID- 11833039
TI  - Declining beta-cell function in type 2 diabetes: 5-year follow-up and immunologic
      studies of the population of Wadena, MN.
AB  - The aim of the study was to describe 5-year changes in meal-stimulated pancreatic
      insulin reserve in adults with normal and impaired glucose tolerance (NGT, IGT)
      and diabetes, with or without islet-related antibodies. This was a 5-year follow
      up of 270 residents of Wadena, MN, of northern European origin, with good kidney
      function, defined as creatinine clearance greater than 60 mL/min/1.73 m(2). The
      subjects comprised a population-based sample originally studied in 1986 to 1987.
      Urine C-peptide (CP), in a 260-minute collection, was the integrated measure of
      insulin secretion; Ensure-Plus (Ross, Columbus, OH) was the liquid meal. Islet
      cytoplasmic antibodies (ICA), insulin autoantibodies (IAA), and glutamate
      decarboxylase antibodies (GAD65ab) were measured. In 182 subjects with NGT, there
      was no mean within-subject change in urine CP over 5 years (P =.34). In 41
      subjects with impaired GT (IGT), there was a moderate, but nonsignificant,
      increase in mean CP, and 6 (15%) subjects increased. In 37 type 2 diabetic
      subjects not taking insulin (type 2-No Ins), who had a mean diabetes duration at
      the 5-year examination of 9.6 +/- 6.3 years, there was a 21% decrease in mean
      urine CP (P =.012), attributable mostly to a major drop in 8 of the 37 subjects
      (22%). Islet-related antibody tests were mostly negative; GAD65ab positivity was
      related to CP decline only among insulin-taking subjects. In summary, in Wadena
      adults, meal-stimulated urine CP was stable or increased over 5 years in subjects
      with NGT and IGT, but CP decreased significantly in about one fifth of type 2-No
      Ins subjects, with no relation to antibody test results.

PMID- 11833040
TI  - Effects of intentional weight cycling on non-obese young women.
AB  - This study investigated the effects of intentional weight cycling in non-obese,
      young women (n = 5; mean age, 24.6 years; mean body mass index [BMI], 20.5
      kg/m(2)). During the first 30 days, the subjects lost more than 4 kg with energy
      restriction alone (first diet period). In the following 14 days, they regained
      more than the weight they had lost by eating ad libitum (free-living period). In
      the subsequent 30 days, they once again lost more than 4 kg with only energy
      restriction (second diet period). Height, weight, waist and hip circumferences,
      body composition, lipid profiles, thyroid hormones, systolic and diastolic blood
      pressures (SBP, DBP), and resting energy expenditure (REE) were examined.
      Measurements were taken at the beginning of the study (day 0), at the end of each
      diet period (day 30 and day 74), the end of the free-living period (day 44), and
      on day 180. The mean change in each variable from baseline (day 0) was used and
      controlled for the baseline value, baseline weight, and change in weight (Delta
      weight). Statistical tests were performed to determine the significance of the
      mean changes in the variables. By day 180, there were significant decreases in
      the subjects' lean body mass (P <.01), serum triiodothyronine (T(3)) (P <.001),
      serum total thyroxine (T(4)) (P <.001), and REE (P <.001), and significant
      elevations of SBP (P <.05) and DBP (P <.001). The lipid profiles had not changed
      except for increased triglycerides (TG). These results suggest that weight
      cycling through energy restriction alone may have negative health consequences in
      non-obese, young women.

PMID- 11833041
TI  - Differential impact of acute and chronic lipotoxicity on gene expression in INS-1
      cells.
AB  - Fatty acids induce abnormal insulin secretion, so-called lipotoxicity, which may
      develop over a period that can span from a few hours to several years. The
      relationship between insulin secretion patterns and the pace of lipotoxicity
      development is, however, sparse. In this study acute lipotoxicity was defined as
      the functional changes in clonal pancreatic beta cells, INS-1 cells, cultured
      with 400 and 1,000 micromol/L palmitate for 2 days. Chronic lipotoxicity was
      demonstrated by exposure of INS-1 cells to 50 and 200 micromol/L palmitate for up
      to 10 weeks. During acute lipotoxicity, basal insulin secretion (BIS), as well as
      glucose- and fatty acid-stimulated insulin secretion, were reduced after 1,000
      micromol/L palmitate exposure. Concomitantly, total cell protein and (3)H
      thymidine incorporation were significantly reduced. In chronic lipotoxicity, BIS
      increased, whereas a decrease in insulin responsiveness to glucose and fatty acid
      (defined as fold increase in insulin compared with BIS) was observed after 5
      weeks in cells cultured with 200 micromol/L palmitate. Carnitine
      palmitoyltransferase I gene expression was induced by palmitate upon acute, as
      well as chronic, exposure. Genes involved in the insulin signal pathway may play
      an important role in the pathogenesis of lipotoxicity in beta cells. Thus,
      insulin receptor substrate-1 and 2 gene expressions were downregulated during
      acute lipotoxicity, while insulin receptor gene expression was suppressed in
      chronic lipotoxicity. In conclusion, insulin secretion and gene expression in INS
      1 cells depends on palminate exposure time and concentration.

PMID- 11833042
TI  - Effects of biotin on glucotoxicity or lipotoxicity in rat pancreatic islets.
AB  - Biotin (vitamin H) plays an important role as a cofactor in glucose or lipid
      metabolism. We showed that biotin potentiated glucose-induced insulin release in
      isolated rat islets, while biotin alone did not affect insulin release. Coculture
      with biotin in islets for 48 hours significantly enhanced glucose-induced insulin
      release or islet insulin content. Similarly, preproinsulin or pancreatic/duodenal
      homeobox-1 (PDX-1) mRNA was also enhanced in islets cultured with biotin for 48
      hours. Furthermore, we measured effects of biotin on beta-cell function under
      glucotoxic or lipotoxic states. In islets cultured with high glucose or palmitate
      for 48 hours, glucose-induced insulin release or islet insulin content
      deteriorated. Coculture with biotin significantly restored glucose-induced
      insulin release or islet insulin content together with the restoration of
      preproinsulin or PDX-1 mRNA. We conclude that biotin exerts its beneficial
      effects on beta-cell dysfunction induced by glucose or free fatty acids probably
      through the enhancement of insulin biosynthesis.

PMID- 11833043
TI  - Thiazolidinediones enhance insulin-mediated suppression of fatty acid flux in
      type 2 diabetes mellitus.
AB  - Type 2 diabetes mellitus is characterized by insulin-resistant glucose and lipid
      metabolism. Thiazolidinediones (TZDs) enhance insulin-mediated glucose disposal,
      but their effects on lipid kinetics are unknown. We evaluated the effect of the
      TZD troglitazone on insulin-mediated suppression of fatty acid and glycerol
      kinetics. Eight obese men and women (body mass index [BMI], 34.1 +/- 2.3 kg/m(2))
      with insulin-requiring type 2 diabetes were studied before and after 12 weeks of
      troglitazone therapy (400 mg/d). Whole-body and abdominal fat masses were
      determined by dual-energy x-ray absorptiometry and magnetic resonance imaging,
      respectively. Palmitate and glycerol rates of appearance (R(a)) into plasma were
      evaluated during a 3-stage hyperinsulinemic euglycemic clamp, which spanned the
      physiologic range of plasma insulin concentrations that regulate lipolysis.
      Troglitazone therapy did not alter body composition. Palmitate and glycerol R(a)
      decreased progressively during each stage of hyperinsulinemia (P <.001).
      Suppression of palmitate R(a) by insulin was greater after than before
      troglitazone therapy (P <.001), whereas glycerol R(a) was unchanged. These
      results demonstrate that TZDs increase insulin-mediated suppression of fatty acid
      release into plasma in obese subjects with type 2 diabetes mellitus, which may
      contribute to their metabolic benefits. However, TZD therapy did not affect whole
      body glycerol R(a), possibly because of upregulation of lipoprotein lipase action
      on plasma triglycerides.

PMID- 11833044
TI  - Protective effect of nitric oxide on isolated rat hepatocytes submitted to an
      oxidative stress.
AB  - We have previously suggested that the nitric oxide-cyclic guanosine monophosphate
      (NO-cGMP) pathway protects both hepatocytes and endothelial cells against liver
      ischemia-reperfusion injury in rat. We study here the ability of NO to protect
      isolated hepatocytes against an in vitro oxidative stress induced with
      hypochlorite solution (ClO(-)). The severity of ClO(-)-induced stress was
      quantified by the measurement of total glutathione and membrane lipid
      peroxidation. Cell damage was assessed by morphologic (cell viability and bleb
      formation) and biologic (transaminase release) criteria. A 30-minute incubation
      of hepatocytes with 100 micromol/L ClO(-) maximally decreased cell viability (
      40%) and increased bleb formation (+300%) and release of transaminases activities
      (aspartate transaminase [AST] = +60% and alanine transaminase [ALT] = +300%). A
      good correlation was observed between morphologic and biologic criteria. A
      preincubation of cells with 50 micromol/L 8-Br-cGMP, did not affect the adverse
      ClO(-) effects on the morphologic criteria. In the presence of 20 micromol/L
      spermineNONOate, an NO donor, ClO(-) did not decrease cell viability, whereas its
      deleterious effects on bleb formation was unchanged. A preincubation with a
      specific inhibitor of the soluble guanylate cyclase, the 1H-[1,2,4]oxadiazolo[4,3
      a]quinoxalin-1-one (ODQ; 1 micromol/L), did not affect the beneficial effect of
      NO on the cell viability. Our results suggest that NO protects hepatocytes
      against oxidative stress by a mechanism, which is cGMP-independent. However,
      taking into account the cytoprotective effects of cGMP in the liver, it is likely
      that the rapid effect of NO observed in vitro is relayed in vivo by a more long
      lasting mechanism, which would be inhibited by ODQ and mimicked by 8-Br-cGMP.

PMID- 11833045
TI  - Total body phosphorus in healthy women and ethnic variations.
AB  - Total body phosphorus (TBP) levels were measured in 90 black and 143 white
      healthy women to determine ethnic differences. The measurements were performed by
      in vivo delayed gamma neutron activation (DGNA) analysis at Brookhaven National
      Laboratory (BNL). Mean value of TBP in whites was 10.4% lower as compared with
      the black women (mean TBP in white women 401.4 +/- 57.5 g v. 447.7 +/- 57.7 g in
      black women). Both subgroups have a decrease in TBP with age with a rapid phase
      after the onset of menopause, which corresponds to bone loss. The decrease in TBP
      is similar in both ethnic groups with black women losing -1.59 g/yr (-0.33%/yr)
      and white women losing -2.08 g/yr (-0.45%/yr).

PMID- 11833046
TI  - Insulin secretion and sensitivity in non-obese and obese Japanese patients with
      coronary artery disease.
AB  - In a cross-sectional study of 240 patients with angiographically documented
      coronary artery disease (CAD), we investigated whether obese and non-obese
      subjects differed as to the influence of insulin deficiency and insulin
      resistance on glucose intolerance and cardiovascular risk. Patients were
      classified according to a 75-g oral glucose tolerance test as having normal
      glucose tolerance (NGT), impaired glucose tolerance (IGT), or diabetes mellitus
      (DM). We defined obesity as a body mass index (BMI) exceeding 25 kg/m(2). Early
      phase insulin secretion (insulinogenic index) declined with worsening glucose
      intolerance in non-obese (tau = -.216, P <.001; Kendall's correlation
      coefficient) and obese subjects (tau = -.392, P <.001). Total insulin secretion
      was higher in obese subjects with NGT or IGT than in controls and decreased in
      association with worsening glucose intolerance in obese subjects (tau = -.239, P
      <.001). Insulin sensitivity was calculated by 3 proposed indices. The first of
      these decreased in association with worsening in glucose tolerance in non-obese
      subjects (tau = -.137, P <.01). The second showed such a pattern in both groups
      (non-obese, tau = -.407, P <.001; obese, tau = -.311, P <.001), as did the third
      (non-obese, tau = -.512, P <.001; obese, tau = -.488, P < 0.001). Because even
      prediabetic Japanese subjects with CAD showed a latent insulin secretion defect
      in response to a glucose load, as well as impaired insulin sensitivity,
      compensatory hyperinsulinemia is not a sensitive indicator of coronary risk.

PMID- 11833047
TI  - Effects of phytosterol ester-enriched margarine on plasma lipoproteins in mild to
      moderate hypercholesterolemia are related to basal cholesterol and fat intake.
AB  - Dietary phytosterols have been reported to lower total and low-density
      lipoprotein (LDL) cholesterol. However, less is known about the influence of
      cholesterol and fat intake on the cholesterol-lowering effect of esterified
      phytosterols in mild to moderate hypercholesterolemia. Sixty-three healthy
      subjects (38 women, 25 men, 42 +/- 11 years, LDL cholesterol > 130 mg/dL) were
      investigated in a randomized, double-blind, placebo-controlled, cross-over study.
      A total of 20 g/d of a phytosterol ester-enriched margarine (1.82 g/d of
      phytosterols) was compared with a control margarine (0.06 g/d of phytosterols).
      After 3 weeks of intake, participants crossed over to the other margarine. A 3
      day dietary recall was performed at the beginning and at the end of the study to
      assess cholesterol, fat, and energy intake. Phytosterol ester-enriched margarine
      significantly changed total cholesterol (-3.4%, P <.005), LDL cholesterol (-5.4%,
      P <.001, 144 +/- 28 v 154 +/- 26 mg/dL), high-density lipoprotein (HDL)
      cholesterol (+3.4%, P <.05), apolipoprotein B (-4.0%, P <.005), and LDL/HDL
      cholesterol ratio (-7.8%, P <.001) compared with the control margarine. In the
      tertiles with the highest dietary intake of cholesterol, energy, total fat, and
      saturated fatty acids, and with the highest baseline proportion of campesterol to
      cholesterol, LDL cholesterol reduction was 11.6% (P <.001), 9.5% (P =.001), 9.4%
      (P =.001), 8.4% (P =.005), and 6.2% (P =.014), respectively. Triglycerides,
      plasma viscosity, and fibrinogen concentration did not change significantly. The
      improvements of LDL, HDL, total cholesterol, apolipoprotein B concentrations, and
      LDL/HDL cholesterol ratio during the daily consumption of a phytosterol ester
      enriched margarine were most marked in those subjects with a high dietary intake
      of cholesterol, energy, total fat, and saturated fatty acids and with high
      baseline cholesterol absorption.

PMID- 11833048
TI  - Men at increased risk of coronary heart disease are not different from age- and
      weight-matched healthy controls in their postprandial triglyceride, nonesterified
      fatty acid, or incretin responses to sucrose.
AB  - Short-term studies suggest that extreme sucrose consumption has a detrimental
      effect on triglycerides (TG) in hypertriglyceridemic people. There is currently
      no consensus on the short-term inclusion of a moderate intake of sucrose in
      middle-aged men at increased risk of coronary heart disease (CHD). It is also
      unknown whether gut hormones that are released in response to carbohydrate
      ingestion modulate any of the effects of sucrose. The aim of this study was to
      further elucidate whether men at increased risk of CHD have an exaggerated
      response to sucrose compared with age- and weight-matched controls over an acute
      postprandial period. Twenty middle-aged men were recruited and separated into
      control (total cholesterol < 5.5 mmol/L) and increased risk of CHD (> 5.5 mmol/L)
      groups. We measured postprandial TG, nonesterified fatty acids (NEFA), insulin,
      glucose, glucagon-like peptide-1 (GLP-1), and gastric inhibitory polypeptide
      (GIP) concentrations in response to a meal containing 75 g glucose or 75 g
      sucrose with a moderate fat load. The increased risk group had significantly
      higher Framingham risk assessment (12% v 4%), TG (2.4 +/- 1.5 v 1.1 +/- 0.4
      mmol/L), low-density lipoprotein-cholesterol (LDL-C) (4.4 +/- 0.5 v 2.7 +/- 0.4
      mmol/L), and lower high-density lipoprotein-cholesterol (HDL-C) (1.2 +/- 0.2 v
      1.5 +/- 0.2 mmol/L) (P <.05 for all). There was no significant difference in the
      incremental area under the curve (IAUC, 0 to 360 minutes) for TG, NEFA, glucose,
      GLP-1, or GIP in response to glucose or sucrose within or between the groups.
      Absolute total area under the curve (not IAUC) for TG was significantly higher in
      the increased risk group for both glucose and sucrose, respectively (P =.01). A
      total of 75 g of sucrose given as part of a single meal appears to make little
      difference in the postprandial TG and NEFA response in men with or without risk
      of CHD compared with glucose. Although long-term data is needed, this begs the
      question whether a moderate intake of sucrose has been overemphasized as a
      detrimental dietary message in middle-aged men.

PMID- 11833049
TI  - Interaction of endothelial cells and triglyceride-rich lipoproteins with
      apolipoprotein E (Arg-->Cys) from a patient with lipoprotein glomerulopathy.
AB  - We saw a patient with proteinuria and characteristics of lipoprotein
      glomerulopathy (LPG). Histologic analysis of renal biopsy showed a thrombus-like
      substance in the markedly dilated glomerular capillaries, which stained positive
      with oil red O. Increased concentration of plasma apolipoprotein E (apoE) was
      also noted. Those findings are consistent with the diagnostic criteria of LPG, as
      reported by Oikawa et al. In isoelectric focusing gel electrophoresis of apoE, a
      band (apoE3') between apoE3 and E2 was observed. The patient's DNA sequence
      exhibited a C to G substitution in exon 3 of the apoE gene at the position of the
      25th amino acid, resulting in an amino acid substitution of the arginine residue
      for cysteine residue. To clarify the pathophysiologic role of this mutation, we
      investigated the binding and the uptake of apoE3' triglyceride-rich lipoproteins
      to human umbilical vein endothelial cells (HUVEC). The binding of apoE3'
      triglyceride-rich lipoproteins to the cell-surface of HUVEC increased up to 30%
      to 50%, compared with apoE3-triglyceride-rich lipoproteins. But the uptake of
      apoE3'-triglyceride-rich lipoproteins into the cells was not different between
      them. These findings are consistent with the idea that an increase in binding of
      triglyceride-rich lipoproteins possessing apoE (Arg(25)-->Cys) to endothelial
      cells may promote deposition of lipid in the glomerular capillaries.

PMID- 11833052
TI  - Lack of agreement between the plasma lipid-based criteria and apoprotein B for
      the diagnosis of familial combined hyperlipidemia in members of familial combined
      hyperlipidemia kindreds.
AB  - Our objective was to analyze the concordance between abnormally high-cholesterol
      and triglyceride concentrations and increased apoliprotein B (apoB)
      concentrations for considering subjects as affected in familial combined
      hyperlipidemia (FCHL) kindreds. Twenty-two FCHL families (n = 217) were included.
      There was a lack of agreement in the identification of the abnormal subjects when
      several cholesterol- and triglyceride-based criteria were compared against
      various apoprotein B-based criteria. The agreement, measured as kappa
      coefficients, between 14 lipid-based criteria and 8 apoB concentrations is
      reported. For the most frequently used criterion (> or = 90th percentile for
      cholesterol or triglyceride concentrations), the agreement was low for all apoB
      levels (kappa, 0.42 to 0.49). A concentration of triglycerides > or = 150 mg/dL
      and cholesterol > or = 200 mg/dL was the only criterion with a kappa value above
      0.6; the acceptable agreement was found with an apoB concentration > or = 120
      mg/dL (kappa = 0.604). In conclusion, the data reported here clearly show that a
      large degree of diagnostic uncertainty exists in the categorization as normal or
      abnormal of members of FCHL kindred. Different diagnostic criteria would result
      in conflicting results. This is a critical issue, depending on the diagnostic
      criteria used, completely different conclusions could result from the linkage
      analysis in the FCHL studies.

PMID- 11833050
TI  - Variation in plasma leptin concentrations after unilateral nephrectomy.
AB  - The temporal changes in plasma leptin concentrations were studied in healthy
      adults who underwent unilateral nephrectomy. Another group who underwent
      abdominal surgery for repair of aneurysm or to relieve arterial stenosis, was
      also studied. Plasma leptin concentrations increased to 230% +/- 74% of
      prenephrectomy levels at 8 to 16 hours after surgery and then generally declined.
      Subjects with prenephrectomy leptin concentrations above 14 microL maintained
      elevated postnephrectomy levels, whereas subjects with low prenephrectomy
      concentrations had final leptin levels below prenephrectomy concentrations.
      Abdominal surgery subjects did not manifest the increase after surgery, but
      generally had declining concentrations throughout the convalescent period. Free
      and bound fractions of plasma leptin and leptin binding capacity were measured in
      the prenephrectomy and peak specimens (8 to 16 hours postnephrectomy) by high
      performance liquid chromatography (HPLC). The increase in total leptin
      postnephrectomy largely affected the free fraction of leptin, without significant
      increase in bound leptin or leptin binding capacity. We conclude that (1) plasma
      leptin concentrations increase acutely after nephrectomy, consistent with the
      role of the kidneys in eliminating circulating leptin; (2) plasma leptin
      concentrations decline thereafter, suggesting activation of compensatory
      elimination capacity; and (3) the postnephrectomy peak in total leptin increases
      primarily free leptin.

PMID- 11833051
TI  - Ethnic differences in postprandial triglyceride response to a fatty meal and
      lipoprotein lipase in lean and obese African American and Caucasian women.
AB  - The purpose of this study was to determine if there were differences in the
      expression of lipoprotein lipase (LPL) in African American (AA) and Caucasian
      (CA) women. LPL mRNA and protein levels were determined in subcutaneous and
      omental fat of lean and obese subject from the 2 races (4 groups; 12 to 15
      subjects/group). LPL mRNA levels of lean AA were not different from the lean CA
      women in either fat depot. LPL mRNA levels in the subcutaneous fat of the obese
      AA were higher than those of CA women (1.3 +/- 0.1 v 0.86 +/- 0.06, P.05), but
      not different in omental fat. LPL mass in subcutaneous fat of lean AA was higher
      (0.95 +/- 0.09 v 0.64 +/- 0.06, P.05), but not different in omental fat from the
      CA women. LPL mass in subcutaneous and omental fat was not different in the 2
      obese groups. Differences in the activity of LPL were evaluated by (1) measuring
      the increments of triglycerides (TG) at 2, 4, 6, and 8 hours after a fat-rich
      meal and (2) by measuring postheparin plasma lipolytic activity. Plasma TG levels
      in the lean AA were lower than those of the lean CA women at basal and at 2, 4,
      6, and 8 hours postprandially. The increase in TG levels at 2 hours tended to be
      lower in the AA than the CA women, was significantly lower at 4 hours (24 +/- 5 v
      45 +/- 7, P.05), and was not different 8 hours postprandially. No differences
      were observed in either the absolute or the incremental concentrations of TG in
      the obese groups. Postheparin plasma LPL activity was higher in the lean AA than
      the lean CA women (4.8 +/- 0.4 v 3.4 +/- 0.4, P.05), but not different in the
      obese groups. These results indicate that the lower TG concentrations in the lean
      AA women may be partly due to enhanced expression, activity, and intravascular
      availability of LPL. Furthermore, it appears that the racial differences in
      expression and function of LPL are attenuated with obesity.

PMID- 11833053
TI  - Effect of increased concentration of D-glucose or L-fucose on monocyte adhesion
      to endothelial cell monolayers and activation of nuclear factor-kappaB.
AB  - Increased adhesion of monocytes to endothelial cells has been linked to the
      development and progression of atherosclerosis in humans with diabetes. Previous
      studies have shown that increased concentration of glucose and subsequent
      generation of reactive oxygen species and the activation of the transcription
      factor nuclear factor-kappaB (NF-kappaB) may mediate this response. However, our
      studies have shown that in addition to glucose, other monosaccharides, such as L
      fucose, which is increased in circulation in diabetes, may also contribute to the
      development of diabetic complications. In these studies, we examined the effect
      of an increased concentration of L-fucose on monocyte adhesion to cultured bovine
      aorta endothelial cells. Exposing cultured bovine aorta endothelial cells to an
      increased concentration of either glucose or L-fucose caused a concentration
      dependent increase in adhesion of monocytes. The increase in monocyte adhesion
      induced by glucose or L-fucose was preceded by the activation to NF-kappaB and
      the generation of reactive oxygen species. The combination of glucose and L
      fucose at a submaximal concentration did not appear to have an additive effect on
      the induction of monocyte adhesion. The addition of alpha-lipoic acid partially
      prevented the glucose and L-fucose-induced activation of NF-kappaB, generation of
      reactive oxygen species, and increase in monocyte adhesion. This suggests that
      the effect of an increased concentration of glucose or L-fucose on monocyte
      adhesion to endothelial cells is at least partially due to the production oxygen
      derived free radicals. Furthermore, these studies provide evidence that
      monosaccharides other than glucose that are increased in the circulation of
      humans with diabetes may contribute to vascular defects in diabetes.

PMID- 11833054
TI  - Evaluation of the quantitative insulin sensitivity check index as an estimate of
      insulin sensitivity in humans.
AB  - The goal of this study was to compare estimates of insulin resistance generated
      by the quantitative insulin sensitivity check index (QUICKI) with a direct
      measure of insulin-mediated glucose disposal in healthy, nondiabetic volunteers.
      For this purpose, the results of measurements of plasma glucose and insulin
      concentrations in 490 nondiabetic, healthy subjects were used to compute several
      surrogate estimates of insulin resistance, and these values were compared with a
      direct measure of insulin-mediated glucose disposal. The results of this analysis
      showed that estimates of insulin resistance derived from use of QUICKI were
      significantly correlated (r = -.60, P <.001) with direct measures of insulin
      mediated glucose in the 490 subjects studied. It was also noted that QUICKI
      estimates of insulin resistance were highly correlated with fasting insulin
      concentrations (r = -.98) and the homeostasis model assessment for insulin
      resistance (HOMA-IR, r = -.99). On the other hand, the correlation between all 3
      of the surrogate methods for estimating insulin resistance and the direct
      assessment of insulin-mediated glucose disposal was relatively weak, i.e., r
      =.61, r =.64, and r = -.60) for fasting insulin concentration, HOMA-IR, and
      QUICKI, respectively. The results of these comparisons do not provide support for
      the superiority of QUICKI over other commonly used surrogate measures of insulin
      resistance based upon use of fasting insulin concentration or equations utilizing
      fasting insulin and glucose concentration. Furthermore, none of the 3 surrogate
      estimates can account for more than approximately 40% of the variability of the
      difference in insulin-mediated glucose disposal measured directly in 490 healthy,
      nondiabetic volunteers.

PMID- 11833055
TI  - Association between hyperinsulinemia and endogenous androgen levels in peri- and
      postmenopausal women.
AB  - We evaluated the relationship between hyperinsulinemia and anthropometric,
      metabolic, and hormonal parameters that might contribute to the risk for coronary
      heart disease (CHD) in 104 peri- and postmenopausal women. Plasma glucose,
      insulin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), sex
      hormone-binding globulin (SHBG), and total testosterone (TT) were determined.
      Free androgen index (FAI) and fasting insulin to glucose ratio (IGR) were
      calculated. The cut off point to define hyperinsulinemia was established at 23
      microIU/mg. Mean age was 54.8 years. Mean age at menopause was 47.7 years. Body
      mass index (BMI) was greater than 25 in 46 patients, and 28 (26.9%) were
      hyperinsulinemic. BMI, waist circumference, triglycerides, and 2-hour postglucose
      insulin levels were significantly higher in hyperinsulinemic patients.
      Hyperinsulinemic patients had higher TT levels (P =.02), FAI (P =.0001), and
      lower SHBG levels (P =.003). Positive correlations were observed between IGR and
      BMI, waist-to-hip ratio (WHR), waist circumference, and triglycerides. IGR and
      high-density lipoprotein-cholesterol (HDL-C) were negatively correlated. IGR
      presented a positive association with TT and FAI and a negative association with
      SHBG. FAI contributed positively to IGR, independently of BMI, age, or time since
      menopause. In conclusion, androgen levels may be important determinants of risk
      factors for cardiovascular diseases in peri- and postmenopausal women. However,
      this observation should be confirmed by longitudinal studies.

PMID- 11833056
TI  - Correlation between common carotid arterial wall thickness and ischemic stroke in
      patients with type 2 diabetes mellitus.
AB  - If a strong association between intima-media thickness of the common carotid
      artery (CCA-IMT) and ischemic stroke can be determined in diabetic subjects, it
      may be a useful predictor to help identify patients at high risk of ischemic
      stroke. To investigate the relative contribution of CCA-IMT to ischemic stroke in
      patients with type 2 diabetes, we measured CCA-IMT and other conventional risk
      factors in 438 Japanese patients with type 2 diabetes, including 45 with ischemic
      stroke and 393 controls. Stroke patients were characteristically and
      significantly older with higher body mass index, longer duration of diabetes,
      likely to be smokers, higher blood pressure, and higher total cholesterol
      compared with the controls. CCA-IMT in stroke patients (1.23 +/- 0.04 mm) was
      significantly greater than in control patients (0.95 +/- 0.01 mm, P <.01). CCA
      IMT in stroke patients was still significantly greater than controls after
      adjustment for age, sex, body mass index, and smoking status (P <.05). A 0.1-mm
      increase in CCA-IMT was associated with 1.80-fold increase in the odds ratio of
      stroke in diabetic patients (95%confidence interval [CI], 1.49 to 2.17; P <.01).
      Four independent factors were found to correlate significantly with CCA-IMT: age,
      systolic blood pressure, HbA(1c), and high-density lipoprotein (HDL) cholesterol.
      Thus, thickening of the intima-media of common carotid arteries is associated
      with ischemic stroke in type 2 diabetic patients. To prevent ischemic stroke,
      strict control of diabetes, hypertension, and dyslipidemia and monitoring of CCA
      IMT may be important.

PMID- 11833057
TI  - Glycemia (or, in women, estimated glucose disposal rate) predict lower extremity
      arterial disease events in type 1 diabetes.
AB  - The purpose of this study was to determine the predictors of lower extremity
      arterial disease (LEAD) events in a type 1 diabetes population. Data are from the
      Pittsburgh Epidemiology of Diabetes Complications Study of childhood onset type 1
      diabetes. At baseline, the study population had a mean age 28 (range, 8 to 47)
      years and duration 19 (range, 7 to 37) years. LEAD events, assessed by
      questionnaire or clinical examination, were defined as claudication (Rose
      questionnaire), foot ulceration, or lower extremity amputation. Estimated glucose
      disposal rate (eGDR), a measure of insulin resistance, was calculated from
      glycosylated hemoglobin (HbA(1)), waist-to-hip ratio (WHR), and hypertension
      using an equation previously validated with hyperinsulinemic euglycemic clamp
      studies. There were incident LEAD events in 70 of 586 subjects during 10 years
      follow-up, giving an incidence density of 1.3 events/100 person-years. Incidence
      did not differ by gender. Major predictors of LEAD events were diabetes duration,
      low-density lipoprotein-cholesterol (LDL-C), heart rate, eGDR, log albumin
      excretion rate (AER), systolic blood pressure (SBP), hypertension, proliferative
      retinopathy, distal symmetric polyneuropathy, and overt nephropathy (each P
      <.001). HbA(1), low ankle brachial index (ABI) (<0.9), and a high ankle brachial
      difference (ABD) (SBP > or = 75 mm Hg) also predicted LEAD events. Cox modeling
      suggested that duration (P <.001), HbA(1) (P <.001), hypertension (P =.006), log
      albumin excretion rate (P =.011), and heart rate (P =.028) predicted events
      independently. The overall model with HbA(1) and hypertension was significantly
      better than with eGDR, while the alternate models in men were similar. In women,
      the model with eGDR showed a significantly better fit. Glycemia, insulin
      resistance, hypertension and renal disease are powerful predictors of symptomatic
      lower extremity arterial disease in type 1 diabetes.

PMID- 11833058
TI  - Relative impact of low-density lipoprotein-cholesterol concentration and insulin
      resistance on carotid wall thickening in nondiabetic, normotensive volunteers.
AB  - The relative effect of an increase in low-density lipoprotein-cholesterol (LDL-C)
      concentration, as compared with insulin resistance and its manifestations, on
      intimal medial thickening (IMT) of the common carotid artery was defined in 72
      healthy men and women. Insulin-mediated glucose disposal was quantified by the
      insulin suppression tests, in which the height of the steady-state plasma glucose
      (SSPG) concentration during the last 30 minutes of a 180-minute infusion of
      octreotide, insulin, and glucose provides an estimate of insulin resistance. IMT
      was determined by high-resolution B-mode ultrasonography. Univariate analyses
      defined statistically significant correlation coefficients between IMT and LDL-C
      concentration (r =.25, P <.05), SSPG concentration (r =.32, P <.01),
      triglycerides (TG) (r =.25, P <.05), and high-density lipoprotein-cholesterol
      (HDL-C) (r = -.28, P <.05) concentrations (changes associated with insulin
      resistance) and ratio of waist-to-hip girth (r =.29, P <.05). When forward step
      wise linear regression analysis was used, concentrations of SSPG, LDL-C and HDL-C
      all emerged as independent predictors of IMT (P <.05). Furthermore, the magnitude
      of their relationship to IMT values was comparable. These results provide
      evidence that insulin resistance is as significant a predictor of degree of
      atherogenesis (estimated by IMT) of the common carotid artery as a high LDL-C
      concentration.

PMID- 11833060
TI  - The influence of hormonal status and features of the metabolic syndrome on bone
      density: a population-based study of Swedish women aged 50 to 59 years. The
      women's health in the Lund area study.
AB  - This study investigated whether there is an association between bone density and
      features of the metabolic syndrome in relation to hormonal status. All women aged
      50 to 59 years living in a defined geographic area in Sweden were offered a
      health assessment program including blood glucose, lipid profile, blood pressure,
      and bone densitometry. Women were divided into 3 groups according to their
      hormonal status: premenopausal (PM), postmenopausal with hormone replacement
      therapy (PMT), and postmenopausal without hormone replacement therapy (PM0). Of
      the 6,886 women investigated, 7% were PM, 41% PMT, and 52% PM0. The overall
      prevalence of osteopenia and osteoporosis, according to the World Health
      Organization (WHO) definition, was 42.6% and 6.6%, respectively. T-score in the
      PM group was higher than in the PMT (P <.05) and PM0 groups (P <.001) and higher
      in the PMT group compared with the PM0 group (P <.001). Also, in the total
      cohort, the bone density was positively associated with body weight, body mass
      index (BMI), waist-to-hip ratio (WHR), systolic blood pressure (SBP), diastolic
      blood pressure (DBP), serum triglycerides, and blood glucose (P <.001 for all)
      and negatively associated with serum levels of cholesterol (P <.05) and high
      density lipoprotein (HDL) (P <.001). This was most evident among the PMO women,
      suggesting that the influence of metabolic factors on bone density increases when
      the levels of hormones decrease. This indicates that hormone replacement therapy
      maintains treated women in a premenopausal status concerning the metabolic
      factors.

PMID- 11833059
TI  - Elevated concentrations of free fatty acids are associated with increased insulin
      response to standard glucose challenge in human immunodeficiency virus-infected
      subjects with fat redistribution.
AB  - Fat redistribution, defined by both increased abdominal visceral fat and/or
      decreased abdominal, extremity, and facial subcutaneous fat, is increasingly
      recognized among human immunodeficiency virus (HIV)-infected patients treated
      with combination antiretroviral therapy. Fat redistribution in this population is
      associated with insulin resistance and dyslipidemia and is often referred to as
      the HIV lipodystrophy syndrome (LIPO). Fatty acids are known to modulate insulin
      resistance in other disease states, but a comprehensive evaluation of fatty acids
      has not been undertaken among HIV-infected patients with fat redistribution. In
      this study, we investigated fatty acid concentrations in 64 HIV-infected
      individuals (45 men and 19 women) with evidence of fat redistribution (LIPO) in
      comparison to 30 HIV-infected individuals (20 men and 10 women) without evidence
      of fat redistribution (NONLIPO) and 32 HIV-negative healthy control subjects (C)
      (21 males and 11 females) of similar age and body mass index (BMI). Glucose,
      insulin, and free fatty acid (FFA) levels were measured in response to a 75-g
      oral glucose tolerance test (OGTT) in the LIPO, NONLIPO, and C subjects. In
      addition, fasting lipids were obtained, and body composition was determined by
      anthropometric measurements and dual-energy x-ray absorptiometry (DXA). Fasting
      FFA concentrations were significantly increased in the LIPO group as compared
      with NONLIPO and C subjects (0.74 +/- 0.03 v 0.60 +/- 0.04 [mean +/- SEM] mmol/L,
      P =.002, LIPO v NONLIPO; 0.74 +/- 0.03 v 0.59 +/- 0.03 mmol/L, P =.001, LIPO v
      C). In contrast, fasting FFA concentrations were not increased in the NONLIPO
      group (0.60 +/- 0.04 v 0.59 +/- 0.03, P =.909, NONLIPO v C). Similarly, fasting
      triglycerides and 120-minute OGTT FFA were significantly increased in the LIPO
      group as compared with the NONLIPO and C group. FFA decreased in HIV-infected
      LIPO, NONLIPO, and C subjects in response to OGTT, but the 120-minute FFA
      concentrations remained significantly elevated in LIPO patients compared with
      NONLIPO and C subjects. In a multivariate regression model of LIPO patients,
      fasting FFA (P =.027) was a strong independent predictor of insulin area under
      the curve (AUC), controlling for age, BMI, gender, and body composition (r(2) for
      model =.31). No differences were observed in FFA concentrations in the LIPO group
      in an analysis based on current protease inhibitor (PI) use. These data suggest
      that FFA concentrations are increased in HIV-infected patients with fat
      redistribution. Increased fasting concentrations of fatty acids are associated
      with abnormal insulin responses to standard glucose challenge in HIV-infected
      patients with fat redistribution. Further studies are necessary to determine the
      mechanism of increased fatty acid concentrations and the role played by increased
      FFA in mediating insulin resistance in this population.

PMID- 11833061
TI  - Experimental models to study cholangiocyte biology.
AB  - Cholangiocytes-the epithelial cells which line the bile ducts-are increasingly
      recognized as important transporting epithelia actively involved in the
      absorption and secretion of water, ions, and solutes. This recognition is due in
      part to the recent development of new experimental models. New biologic concepts
      have emerged including the identification and topography of receptors and flux
      proteins on the apical and/or basolateral membrane which are involved in the
      molecular mechanisms of ductal bile secretion. Individually isolated and/or
      perfused bile duct units from livers of rats and mice serve as
      new,physiologically relevant in vitro models to study cholangiocyte transport.
      Biliary tree dimensions and novel insights into anatomic remodeling of
      proliferating bile ducts have emerged from three-dimensional reconstruction using
      CT scanning and sophisticated software. Moreover, new pathologic concepts have
      arisen regarding the interaction of cholangiocytes with pathogens such as
      Cryptosporidium parvum. These concepts and associated methodologies may provide
      the framework to develop new therapies for the cholangiopathies, a group of
      important hepatobiliary diseases in which cholangiocytes are the target cell.

PMID- 11833062
TI  - Changing patterns of traumatic bile duct injuries: a review of forty years
      experience.
AB  - AIM: To summarize the experiences of treating bile duct injuries in 40 years of
      clinical practice. METHODS: Based on the experience of more than 40 years of
      clinical work, 122 cases including a series of 61 bile duct injuries of the
      Southwest Hospital, Chongqing, and 42 cases (1989-1997) and 19 cases (1998-2001)
      of the General Hospital of PLA, Beijing, were reviewed with special reference to
      the pattern of injury. A series of cases of the liver and the biliary tract
      injuries following interventional therapy for hepatic tumors, most often
      hemangioma of the liver, were collected. Chinese medical literature from 1995 to
      1999 dealing with 2742 traumatic bile duct strictures were reviewed. RESULTS:
      There was a changing pattern of the bile duct injury. Although most of the cases
      of bile duct injuries resulted from open cholecystectomy, other types from other
      type of trauma such as laparoscopic cholecystectomy (Lc) and hepatic surgery were
      increased in recent years. Moreover, serious hepato-biliary injuries following
      HAE using sclerotic agents such as sodium morrhuate and absolute ethanol for the
      treatment of hepatic hemangiomas were encountered in recent years. Experiences in
      how to avoid bile duct injury and to treat traumatic biliary strictures were
      presented. CONCLUSION: Traumatic bile duct stricture is one of the serious
      complications of hepato-biliary surgery, its prevalence seemed to be increased in
      recent years. The pattern of bile duct injury was also changed and has become
      more complicated. Interventional therapy with sclerosing agents may cause serious
      hepatobiliary complications and should be avoided.

PMID- 11833064
TI  - Early diagnosis for colorectal cancer in China.
AB  - AIM: To review the present studies on early diagnosis of colorectal cancer.
      METHODS: The detective rate for early cancer is 1.7%-26.1% based on various
      statistical data, with much higher detective rate in endoscopy. Since early
      cancer means invasion involved in the mucosa or submucosa, the diagnosis can only
      be made when the invasive depth is identified. Pathological tissue materials from
      both surgical operation or endoscopic resection are suitable for early cancer
      evaluation. RESULTS: Incidence of polyp malignancy is 1.4%-20.4%. The various
      constitutive proportion of polyps may explain the different rates. Malignant
      incidence is higher in adenomatous polyps, that for villous polyps can reach
      21.3%-58.3%. Type II early stage of colorectal carcinoma is rarely reported in
      China. It is shown that majority of them were not malignant, most of type IIa
      being adenoma or hyperplasia, and IIb being inflammatory and IIc might be the
      isolated ulcers. The occurrence of malignancy of type II is far lower than that
      of polypoid lesion. In China, the qualitative diagnosis and classification of
      neoplasm generally adopted the WHO standard, including surgical excision or
      biopsies. There is impersonal evaluation between colorectal pre-malignancy and
      cancer. The former emphasizes the dysplasia of nuclei and gland, while the latter
      is marked with cancer invasion. Diagnosis of early stage colorectal cancer in
      endoscopy is made with too much caution which made the detective rate much lower.
      Mass screening for asymptomatic subjects and follow-up for high risk population
      are mainly used to find the early stage colorectal cancer in China. Fecal occult
      blood test is also widely made as primary screening test, galactose oxygenase
      test of rectal mucus (T antigen), fecal occult albumin test are also used. The
      detective rate of colorectal cancer is 24-36.5 per 105 mass population.
      CONCLUSION: Although carcinoma associated antigen in blood or stool,
      microsatellite DNA instability for high risk familial history, molecular biology
      technology for stool oncogene or antioncogene, telomerase activity and
      exfoliative cytological examination for tumor marker, are utilized, none of them
      is used in mass screening by now.

PMID- 11833063
TI  - The management of patients with the short bowel syndrome.
AB  - The surgeon is invariably the primary specialist involved in managing patients
      with short bowel syndrome. Because of this they will play an important role in co
      ordinating the management of these patients. The principal aims at the initial
      surgery are to preserve life, then to preserve gut length, and maintain its
      continuity. In the immediate postoperative period, there needs to be a balance
      between keeping the patient alive through the use of TPN and antisecretory agents
      and promoting gut adaptation with the use of oral nutrition. If the gut fails to
      adapt during this period, then the patient may require therapy with more specific
      agents to promote gut adaptation such as growth factors and glutamine. If
      following this, the patient still has a short gut syndrome, then the principal
      options remain either long term TPN, or intestinal transplantation which remains
      a difficult and challenging procedure with a high mortality and morbidity due to
      rejection.

PMID- 11833065
TI  - RRR-alpha-tocopheryl succinate inhibits human gastric cancer SGC-7901 cell growth
      by inducing apoptosis and DNA synthesis arrest.
AB  - AIM: To investigate the effects of growth inhibition of human gastric cancer SGC
      7901 cell with RRR-alpha-tocopheryl succinate (VES), a derivative of natural
      Vitamin E, via inducing apoptosis and DNA synthesis arrest. METHODS: Human
      gastric cancer SGC-7901 cells were regularly incubated in the presence of VES at
      5, 10 and 20mg x L(-1) (VES was dissolved in absolute ethanol and diluted in RPMI
      1640 complete condition media correspondingly to a final concentration of VES and
      1 mL x L(-1) ethanol), succinic acid and ethanol equivalents as vehicle (VEH)
      control and condition media only as untreated (UT) control. Trypan blue dye
      exclusion analysis and MTT assay were applied to detect the cell proliferation.
      Cells were pulsed with 37kBq of tritiated thymidine and (3H) TdR uptake was
      measured to observe DNA synthesis. Apoptotic morphology was observed by electron
      microscopy and DAPI staining. Flow cytometry and terminal deoxynucleotidyl
      transferase-mediated dUTP nick end labeling (TUNEL) assay were performed to
      detect VES-triggered apoptosis. RESULTS: VES inhibited SGC-7901 cell growth in a
      dose-dependent manner. The growth curve showed suppression by 24.7%, 49.2% and
      68.7% following 24h of VES treatment at 5, 10 and 20 mg x L(-1), respectively,
      similar to the findings from MTT assay. DNA synthesis was evidently reduced by
      35%, 45% and 98% after 24h VES treatment at 20mg x L(-1) and 48 h at 10 and 20mg
      x L(-1), respectively. VES induced SGC-7901 cells to undergo apoptosis with
      typically apoptotic characteristics, including morphological changes of chromatin
      condensation, chromatin crescent formation/margination, nucleus fragmentation and
      apoptotic body formation, typical apoptotic sub-G1 peak by flow cytometry and
      increase of apoptotic cells by TUNEL assay in which 90% of cells underwent
      apoptosis after 48 h of VES treatment at 20 mg x L(-1). CONCLUSION: VES can
      inhibit human gastric cancer SGC-7901 cell growth by inducing apoptosis and DNA
      synthesis arrest. Inhibition of SGC-7901 cell growth by VES is dose- and time
      dependent. Therefore VES can function as a potent chemotherapeutic agent against
      human gastric carcinogenesis.

PMID- 11833067
TI  - The sensitivity of digestive tract tumor cells to As2O3 is associated with the
      inherent cellular level of reactive oxygen species.
AB  - AIM: To explore the correlation of the inherent cellular ROS level with the
      susceptibility of the digestive tract tumor cells to apoptosis inducted by As2O3.
      METHODS: Two gastric carcinoma cell lines, SGC7901 and MKN45, and two esophageal
      carcinoma cell lines, EC/CUHK1(alternatively named EC1.71) and EC1867 with low
      concentration(2 micromol x L(-1))of As2O3 were cultured espectly, which confirmed
      the difference in apoptosis susceptibility between SGC7901 and MKN45, and between
      EC/CUHK1 and EC1867. The cells were incubated with dihydrogenrhodamine123
      (DHR123), used as a ROS capture in absence of As2O3. The fluorescent intensity of
      rhodamine123, which was the product of cellular oxidation of DHR123, was detected
      by flow cytometry, and ROS was measured. RESULTS: Apoptosis induced by a low
      concentration of As2O3 was more readily to occur in SGC7901(22.4%+/-2.4%) and
      EC/CUHK1(27.0%+/-2.9%) than in MKN45(2.1%+/-0.5%) and EC1867(0.8%+/-0.5%). In
      other words, SGC7901 was more sensitive than MKN45 to As2O3, meanwhile EC/CUHK1
      was more sensitive than EC1867 to As2O3. The level of inherent cellular ROS in
      SGC7901(650+/-37) was higher than that in MKN45(507+/-22)(P<0.01), and the level
      of inherent cellular ROS in EC/CUHK1(462+/-17) was higher than that in
      EC1867(187+/-12)(P<0.01). CONCLUSIONS: The cellular sensitivity to apoptosis
      induced by As2O3 is associated with the difference in cellular ROS level. The
      inherent ROS level might determinate the apoptotic sensitivity of tumor cells to
      As2O3.

PMID- 11833066
TI  - Morphological and functional changes of mitochondria in apoptotic esophageal
      carcinoma cells induced by arsenic trioxide.
AB  - AIM: To demonstrate that mitochondrial morphological and functional changes are
      an important intermediate link in the course of apoptosis in esophageal carcinoma
      cells induced by As2O3. METHODS: The esophageal carcinoma cell line SHEEC1,
      established in our laboratory, was cultured in 199 growth medium, supplemented
      with 100mL x L(-1) calf serum and 3 mol x L(-1)As2O3 (the same below). After 2,
      4, 6, 12, 24 h of drug adding, the SHEEC1 cells were collected for light-and
      electron-microscopic examination. The mitochondria were labeled by Rhodamine
      fluorescence probe and the fluorescence intensity of the mitochondria was
      measured by flow cytometer and cytofluorimetric analysis. Further,the
      mitochondrial transmembrane potential (MTP, psim) change was also calculated.
      RESULTS: The mitochondrial morphological change after adding As2O3 could be
      divided into three stages. In the early-stage (2-6h) after adding As2O3, an
      adaptive proliferation of mitochondria appeared; in the mid-stage (6-12 h) a
      degenerative change was observed; and in the late-stage (12-24 h) the
      mitochondria swelled with outer membrane broken down and then cells death with
      apoptotic changes of nucleus. The functional change of the mitochondria indicated
      by fluorescent intensity, which reflected the MTP status of mitochondria, was in
      accordance with morphological change of the mitochondria. The fluorescent
      intensity increased at early-stage, declined in mid-stage and decreased to the
      lowest in the late-stage. 24 h after As2O3 adding, the cell nucleus showed
      typical apoptotic changes. CONCLUSION: Under the inducement of As2O3, the early
      apoptotic changes of SHEEC1 cells were the apparent morphological and functional
      changes of mitochondria, afterwards the nucleus changes followed. It is
      considered that changes of mitochondria are an important intermediate link in the
      course of apoptosis of esophageal carcinoma cells induced by As2O3.

PMID- 11833068
TI  - Nitric oxide and calcium ions in apoptotic esophageal carcinoma cells induced by
      arsenite.
AB  - AIM: To Quantitatively analyze the nitric oxide (NO) and Ca2+ in apoptosis of
      esophageal carcinoma cells induced by arsenic trioxide (As2O3). METHODS: The cell
      line SHEEC1, a malignant esophageal epithelial cell induced by HPV in synergy
      with TPA in our laboratory, was cultured in a serum-free medium and treated with
      As2O3. Before and after administration of As2O3, NO production in cultured medium
      was detected quantitatively using the Griess Colorimetric method. Intracellular
      Ca2+ was labeled by using the fluorescent dye Fluo3-AM and detected under
      confocal laser scanning microscope (CLSM), which was able to acquire data in real
      time enabling Ca2+ dynamics of individual cells in vitro. The apoptotic cells
      were examined under electron microscopy. RESULTS: Intracellular concentration of
      Ca2+ increased from 1.00 units to 1.09-1.38 units of fluorescent intensity at
      As2O3 treatment and NO products subsequently released from As2O3-treated cells
      increased from 0.98-1.00 x10(-2)micromol x L(-1) up to 1.48-1.52 x10(-2)micromol
      x L(-1) and maintained in a high level continuously. Finally apoptosis of cells
      occurred,chromatin being agglutinated, cells shrunk,nuclei became round and
      mitochondria swelled. CONCLUSION: Ca2+ and NO increased with cell damage and
      apoptosis in cells treated by As2O3. The Ca2+ is an initial messenger to the
      apoptotic pathway. To investigate Ca2+ and NO will be a new direction for
      studying the apoptotic signaling messenger of the esophageal carcinoma cells
      induced by As2O3.

PMID- 11833069
TI  - VEGF165 antisense RNA suppresses oncogenic properties of human esophageal
      squamous cell carcinoma.
AB  - AIM: To investigate the effect of antisense RNA to vascular endothelial growth
      factor165 (VEGF165) on human esophageal squamous cell carcinoma cell line EC109
      and the feasibility of gene therapy for esophageal carcinoma. METHODS: By using
      subclone technique, the full length of VEGF165 amino acid cDNA, which was cut
      from pGEM-3Zf+,was cloned inversely into the eukaryotic expression vector pCEP4.
      The recombinant plasmid pCEP-AVEGF165 was transfected into EC109 cell with
      lipofectamine. After a stable transfection, dot blot, enzyme-linked immunosorbent
      assay (ELISA),laser confocal imaging system analysis, transmission electron
      microscopy and flow cytometry were performed to determine the biological
      characteristics of EC109 cell line before and after transfection in vitro and
      whether there was a reversion in the tumorigenic properties of the EC109 cell in
      vitro. RESULTS: The eukaryotic expression vector pCEP-AVEGF165 was successfully
      constructed and transfected into EC109 cells. The expression of VEGF165 was
      significantly decreased in the transfected cells while the biological
      characteristics of the cells were not influenced by the expression of antisense
      gene. The tumorigenic and angiogenic capabilities were greatly reduced in nude
      mice, as demonstrated by reduced tumor end volume (820+/-112.5)mm(3) vs (7930+/
      1035)mm(3) and (7850+/-950)mm(3), P<0.01) and microvessel density (average
      number: (8.5+/-1.2)mm(-2) vs (44.3+/-9.4)mm(-2) and (46.4+/-12.6)mm(-2), P<0.01)
      in comparison between experimental groups empty vector transfected group and
      control group. CONCLUSION: The angiogenesis and tumorigenicity of human
      esophageal squamous cell carcinoma were effectively inhibited by VEGF165
      antisense RNA. Antisense RNA to VEGF165 can potentially be used as an adjuvant
      therapy for solid tumors.

PMID- 11833070
TI  - Relationship of tobacco smoking  CYP1A1  GSTM1 gene polymorphism and esophageal
      cancer in Xi'an.
AB  - AIM: To analyze the association of tobacco smoking polymorphism of CYP1A1 (7th
      exon) and GSTM1 genotype and esophageal cancer(EC) in Xi'an. METHODS: A hospital
      based case-control study, with molecular epidemiological method, was carried out.
      Polymorphism of CYP1A1 and GSTM1 of samples from 127 EC cases and 101 controls
      were detected by PCR method. RESULTS: There were no significant difference of age
      and gender between cases and controls. Tobacco smoking was the main risk factor
      OR=1.97;95% CI=1.12-3.48 for EC in Xi'an. The proportions of CYP1A1 Ile/Ile,
      Ile/Val and Val/Val gene types in cases and controls was 19.7% 45.7% 34.6% and
      30.7%,47.5%, 21.8% respectively(P=0.049). Individuals with CYP1A1 Val/Val
      genotype compared to those with CYP1A1 Ile/Ile genotype had higher risk for EC
      increased (OR=2.48, 95%CI=1.12-5.54). The proportions of GSTM1 deletion genotype
      in cases and controls were 58.3% and 43.6%(OR=1.81, 95%CI=1.03-3.18, P=0.028).
      Analysis of gene-environment interaction showed that tobacco smoking and CYP1A1
      Val/Val genotype; tobacco smoking and GSTM1 deletion genotype had synergism
      interaction respectively. Analysis of gene-gene interaction did not find
      synergistic interaction between these two genes. But in GSTM1 deletion group
      there was significant difference of distribution of CYP1A1 genotype between cases
      and controls (P=0.011). CONCLUSION: CYP1A1 Val/Val and GSTM1 deletion genotypes
      are genetic susceptibility biomarkers for EC. The risk increases, when person
      with CYP1A1 Val/Val and/or GSTM1 deletion genotype. And these two-metabolic
      enzymes seem to have interactions with tobacco smoking, in which the mechanism
      still needs further study.

PMID- 11833071
TI  - Differential display of vincristine-resistance-related genes in gastric cancer
      SGC7901 cell.
AB  - AIM: To isolate and clone the vincristine-resistance-related genes in gastric
      cancer SGC7901 cell line and to clarify the multidrug-resistant molecular
      mechanism of gastric cancer cells. METHODS: The modified differential-display
      polymerase chain reaction (DD-PCR) was used to examine differences in the mRNA
      composition of Vincristine-resistant gastric cancer SGC 7901 cells (SGC7901/VCR),
      induced by vincristine sulfate versus SGC7901cells. The differentially expressed
      cDNA fragments were confirmed by reverse Northern analysis, sequencing, BLAST
      analysis and Northern bolt analysis. RESULTS: The DD-PCR identified that 54 cDNA
      fragments were preferentially expressed in SGC 7901/VCR cells. When these cDNA
      fragments were analyzed by reverse Northern blot, twenty were reproducibly
      expressed at high level in SGC7901/VCR. Sequencing and BLAST analysis revealed
      that seven of the genes were known genes:ADP-ribosylation factor 4, Cytochrome
      oxidase subunit II, Ss-A/Ro ribonucleoprtein autoantigen 60kd subunit,ribosomal
      protein S13, galaectin-8 gene, oligophrenin 1 mRNA, ribosomal protein L23 mRNA;
      thirteen of the genes were unknown genes. The length and abundance of the four
      unknown genes were further confirmed by Northern blot analysis. CONCLUSION: The
      twenty differential known and unknown genes may be related to the vincristine
      resistant mechanism in human gastric cancer SGC7901 cell line.

PMID- 11833072
TI  - Overexpression of cyclin E in Mongolian gerbil with Helicobacter pylori-induced
      gastric precancerosis.
AB  - AIM: To explore dysregulation of cyclin E in malignancies, and to further
      investigate the role of cyclin E in Helicobacter pylori (H. pylori)-induced
      gastric precancerosis. METHODS: Four-week-old specific pathogen-free male
      Mongolian gerbils were employed in the study. 0.5 mL 1 x 10(8) cfu x L(-1)
      suspension of H.pylori NTCC11637 in Brucella broth was inoculated orally into
      each of 20 Mongolian gerbils, and a further 20 gerbils were inoculated with
      Brucella broth as controls. 10 of the infected gerbils and 10 of the non-infected
      control gerbils were sacrificed at 25, 45 wk after infection. The expression of
      cyclin E was analyzed by RT-PCR and immunohistochemical studies with monoclonal
      antibody to cyclin E in Mongolian gerbil of H. pylori-induced gastric
      precancerosis. RESULTS: H. pylori was constantly detected in all infected animals
      throughout the study. At 25 wk after infection of H. pylori, ulcers were observed
      in the antral and body of stomach (n=6). Histological examination showed that all
      animals developed severe inflammation and multifocal lymphoid follicles appeared
      in the lamina propria and submucosa of gastric antrum. At 45 wk after infection
      of H. pylori, severe atrophic gastritis (n=10), intestinal metaplasia (n=8) and
      dysplasia (n=6) could be observed. Cyclin E mRNA levels were significantly more
      at 25 wk after infection of H. pylori (1.27+/-0.26), and at 45 wk after infection
      of H. pylori (1.82+/-0.39) than control-animals (0.59+/-0.20, P<0.01) cyclin E
      mRNA levels were evaluated by 2.2-fold at 25 wk (P<0.01) and 3.1-fold at 45 wk
      (P<0.01) precancerosis induced by H. pylori, when compared with control gastric
      epithelium of Mongolian gerbil. Immunohistochemical staining revealed exclusive
      nuclear staining of cyclin E. Furthermore, there was a sequential increase in
      cyclin E positive cells from normal epithelium to precancerosis. CONCLUSION:
      Overexpression of cyclin E occurs relatively early in gastric tumorigenesis in
      this model.

PMID- 11833073
TI  - Expression of gap junction genes connexin32 and connexin43 mRNAs and proteins,
      and their role in hepatocarcinogenesis.
AB  - AIM: To investigate the relationship between hepatocarcinogenesis and the
      expression of connexin32 (cx32), connexin43 (cx43) mRNAs and proteins in vitro.
      METHODS: Gap junction genes cx32 and cx43 mRNA in hepatocellular carcinoma cell
      lines HHCC, SMMC-7721 and normal liver cell line QZG were detected by in situ
      hybridization (ISH) with digoxin-labeled cx32, and cx43 cDNA probes. Expression
      of Cx32 and Cx43 proteins in the cell lines was revealed by indirect immuno
      fluorescence and flow cytometry (FCM). RESULTS: Blue positive hybridization
      signals of cx32 and cx43 mRNAs detected by ISH with cx32 and cx43 cDNA probes
      respectively were located in cytoplasm of cells of HHCC, SMMC-7721 and QZG. No
      significant difference of either cx32 mRNA or cx43 mRNA was tested among HHCC,
      SMMC-7721 and QZG (P=2.673, HHCC vs QZG; P=1.375, SMMC-7721 vs QZG). FCM assay
      showed that the positive rates of Cx32 protein in HHCC, SMMC-7721 and QZG were
      0.7%, 1.7% and 99.0%, and the positive rates of Cx43 protein in HHCC, SMMC-7721
      and QZG were 7.3%, 26.5% and 99.1% respectively. Significant differences of both
      Cx32 and Cx43 protein expression existed between hepatocellular carcinoma cell
      lines and normal liver cell line (P=0.0069, HHCC vs QZG; P=0.0087, SMMC-7721 vs
      QZG). Moreover, the fluorescent intensities of Cx32 and Cx43 proteins in HHCC,
      SMMC-7721 were lower than that in QZG. CONCLUSIONS: Hepatocellular carcinoma cell
      lines HHCC and SMMC-7721 exhibited lower positive rates and fluorescent
      intensities of Cx32, Cx43 proteins compared with that of normal liver cell line
      QZG. It is suggested that lower expression of both Cx32 and Cx43 proteins in
      hepatocellular carcinoma cells could play pivotal roles in the
      hepatocarcinogenesis. Besides, genetic defects of cx32 and cx43 in post
      translational processing should be considered.

PMID- 11833075
TI  - High-dose iodized oil transcatheter arterial chemoembolization for patients with
      large hepatocellular carcinoma.
AB  - AIM: To conduct a randomized trial to evaluate the role of using high-dose
      iodized oil transcatheter arterial chemoembolization (TACE) in the treatment of
      large hepatocellular carcinoma (HCC). METHODS: From January 1993 to June 1998,
      473 patients with unresectable hepatocellular carcinoma were divided into two
      groups: 216 patients in group A received more than 20 mL iodized oil during the
      first TACE treatment; 257 patients in group B received 5-15 mL iodized oil in the
      same way. The Child's classification and ICG-R15 for evaluating the liver
      function of the patients were done before the treatment. During the TACE
      procedure the catheters were inserted into the target artery selectively and the
      tumor vessels were demonstrated with contrast medium in the hepatic
      angiography.The anticancer drugs mixed with iodized oil (Lipiodol) were
      Epirubicin and Mitomycin. In group A, 112 cases received 20-29 mL Lipiodol in the
      first procedure, 85 cases 30-39 mL, 19 cases more than 40 mL. The largest dose
      was 53 mL and the average dose was 28.3 mL. In group B, 119 cases received 5-10
      mL Lipiodol,138 cases received 11-15 mL and the average dose was 11.8 mL.
      RESULTS: High-dose Lipiodol chemoembolization had tolerable side effects and a
      little hurt to the liver function in the patients with Child's A or ICG-R15<20.
      But the patients with child's B or ICG-R15>20 had higher risk of liver failure
      after high-dose TACE. More type I and type II in CT scan after 4 weeks of TACE
      were seen in the patients of group A than those in the patients of group B
      (P<0.01). The resection rate and complete tumor necrosis rate of group A were
      higher than those of group B (P<0.05). The 1-,2-, 3-year survival rates of group
      A patients with Child's A were 79.2 , 51.8 and 34.9 , respectively, better than
      those of group A (P<0.001). CONCLUSION: High-dose Lipiodol can result in more
      complete tumor necrosis by blocking both arteries and small portal vein of the
      tumor. High-dose TACE for treatment of large and hypervascular hepatocellular
      carcinoma is practically acceptable with the better effect than the routine dose.
      For the patients with large and hypervascular tumor of Child grade A liver
      function or ICG-R15 less than 20%, oily chemoembolization with 20-40 mL Lipiodol
      is recommended.

PMID- 11833074
TI  - Pharmacokinetics of radioimmunotherapeutic agent of direct labeling mAb 188Re
      HAb18.
AB  - AIM: To label anti-hepatoma monoclonal antibody (mAb) fragment HAb18 F(ab')2 was
      labeled with 188Re for the pharmacokinetic model of 188Re-HAb18 F(ab')2 and to
      evaluate its pharmacokinetic parameters in hepatoma-bearing nude mice. METHODS:
      HAb18 F(ab')2 was directly labeled with 188Re using 2-mercaptoethanol (2-ME) as
      reducing agents. Labeling efficiency and immunoreactivity of 188Re-HAb18 F(ab')2
      were evaluated by Whatman 3MM paper chromatography and live cell assay,
      respectively. Biodistribution analysis was also conducted in nude mice bearing
      human hepatoma in which animals were sacrificed at different time points (1, 4,
      18, 24 and 24h) after 188Re-HAb18 F(ab')2 was injected through tail-vein into
      hepatoma-bearing nude mice. The blood and radioactivity of organs and mass were
      measured. The concentrations of (188)Re-HAb18 F(ab')2 were evaluated with a
      pharmacokinetic 3P97 software. RESULTS: The optimum labeling efficiency and
      immunoreactive fraction were 91.7% and 0.78% respectively. The parameters of
      188Re-HAb18 F(ab')2 were: T (1/2),2.29 h;Vd,1.49 x 10(-9)L x Bq(-1);AUC, 20.49 x
      10(9)Bq x h x L(-1);CL, 0.45 x 10(-3)L x h(-1). 188Re-HAb18 F(ab')2 could locate
      specially in hepatoma with high selective reactivity of HAb18 F(ab')2. 188Re
      HAb18 F(ab')2 was mainly eliminated by kidney. The maximal tumor to blood ratio
      was at 48 h,and maximal tumor to liver ratio was at 18 h. CONCLUSION: The
      pharmacokinetics of 188Re-HAb18 F(ab')2 fit a l-compartment model. 188Re-HAb18
      F(ab')2 can be uptaken selectively at the hepatoma site.

PMID- 11833076
TI  - Anti-hepatoma activity of resveratrol in vitro.
AB  - AIM: To study the anti-tumor effect of resveratrol alone and the synergistic
      effects of resveratrol with 5-FU on the growth of H22 cells line in vitro.
      METHODS: The number of cells was measured by MTT method the morphological changes
      of H22 cells were investigated under microscopy and electron microscopy
      examination. RESULTS: Resveratrol inhibited the growth of hepatoma cells line H22
      in a dose- and time-dependent manner, IC50 of the resveratrol on H22 cells was
      6.57mg x L(-1),The synergistic anti-tumor effects of resveratrol with 5-FU
      increased to a greater extent than for H22 cells treated with 5-FU alone (70.2%
      vs 28.4%) P<0.05 .Under microscope and electron microscope, characteristics of
      apoptosis such as typical apoptotic bodies were commonly found in tumor cells in
      the drug-treated groups. CONCLUSION: Resveratrol can suppresses the growth of H22
      cells in vitro,its anti-tumor activity may occur through the induction of
      apoptosis.

PMID- 11833077
TI  - Characterization of focal hepatic lesions with SPIO-enhanced MRI.
AB  - AIM: To evaluate the value of superparamagnetic iron oxide (SPIO) enhanced MRI in
      characterizing focal hepatic lesions. METHODS: Forty-three patients (32 men,11
      women, mean age 51 years, age range 25-74 years) with previously identified focal
      hepatic lesions were enrolled into this study. All the patients underwent plain,
      Gd-DTPA enhanced MRI and the SPIO enhanced MRI 1-7 d later. The surgico
      pathologic diagnosis was aestablished in 31 cases and the diagnosis in other 12
      cases was made on the basis of clinical findings and biochemical tests. The
      signal changes of lesions were analyzed and the CNRs of lesion-to-liver were
      measured before and after SPIO enhancement. The data were analyzed by paired t
      test. RESULTS: Focal hepatic lesions included primary hepatocellular carcinoma
      (HCC,n=22), hemangioma (n=5), cyst (n=4), metastases (n=5), cirrhotic nodule
      (n=4), focal nodular hyperplasia (FNH, n=5) and other miscellaneous lesions
      (n=6). After SPIO enhancement HCC demonstrated iso- or slight hyperintensity on
      T1WI and moderate hyperintersity on T2WI, hemangioma showed moderate
      hyperintensity on T1WI and obvious hyperintensity on T2WI, the SI of cyst had no
      change either on T1WI or on T2WI, cirrhotic nodules revealed iso-intensity on
      T2WI, and the SI of FNH decreased significantly on T2WI. No specific
      manifestations were found in the other 6 miscellaneous lesions after SPIO
      enhancement. CONCLUSION: SPIO enhanced-MRI can improve the characterization
      confidence for diagnosis of focal hepatic lesions.

PMID- 11833078
TI  - Antitumor activities of human dendritic cells derived from peripheral and cord
      blood.
AB  - AIM: To observe the biological specialization of human peripheral blood dendritic
      cells (DC) and cord blood derived DC and its effects on effector cells killing
      human hepatocarcinoma cell line BEL-7402. in vitro. METHODS: The DC biological
      characteristics were detected with immunohistochemical and MTT assay. Two
      antitumor experiment groups are divided: peripheral blood DC and cord blood DC
      groups. Peripheral blood DC groups used LAK cells as the effector cells and BEL
      7402 as target cells, while cord blood DC groups used CTL induced by tumor
      antigen twice pulsed DC as effector cells and BEL-7402 as target cells,
      additional peripheral blood DC and cord blood DC are added to observe its
      stimulating activities to effector cells. The effector's cytotoxicity to tumor
      cells were detected with neutral red colorimetric assay at two effector/target
      ratios of 5:1 and 10:1. RESULTS: Peripheral blood DC and cord blood DC highly
      expressed HLA-ABC, HLA-DR, HLA-DQ, CD54 and S-100 protein. The stimulating
      activities to lymphocyte proliferation were compared between experimental groups
      (DC added) and control group (no DC added), in six experiment subgroups,the
      DC/lymphocyte ratio was sequentially 0.25:100, 0.5:100, 1:100, 2:100, 4:100 and
      8:100.A values were sequentially 0.75396+/-0.009, 0.84916+/-0.010, 0.90894+/
      0.012, 0.98371+/-0.007, 1.01299+/-0.006 and 1.20384+/-0.006 in peripheral blood
      DC groups and 0.77650+/-0.005, 0.83008+/-0.007, 0.92725+/-0.007, 1.05990+/-0.010,
      1.15583+/-0.011, 1.22983+/-0.011 in cord blood DC groups. A value was 0.59517+/
      0.005 in control group. The stimulating activities were higher in experimental
      groups than in control group (P<0.01), which were increased when the DC
      concentration was enlarged (P<0.01). Two differently derived DCs had the same
      phenotypes and similar stimulating activities (P<0.05). In peripheral blood DC
      groups, the cytotoxicity of the LD groups (experimental groups) and L groups
      (control group) was 58.16%+/-2.03% (5:1), 46.18%+/-2.25% (10:1) and 38.13%+/
      1.29% (5:1) and 65.40%+/-1.56% (10:1) respectively; in cord blood DC groups, TD
      groups (experimental groups) and T groups (control groups) were 69.71%+/-2.33 %
      (5:1), 77.64%+/-1.94% (10:1) and 56.89%+/-1.82% (5:1) and 60.99%+/-1.42% (10:1)
      respectively.The cytotoxicity activities were enhanced with increased
      effector/target ratio (P<0.01). At the same effector/target ratio, the
      cytotoxicity of experimental groups were bigger than that of control groups
      (P<0.01). The cytotoxicity activities of cord blood DC groups were higher than
      that of peripheral blood DC groups (P<0.01). CONCLUSION: Peripheral blood DC and
      cord blood DC are mature DC in morphology and function, both can enhance the
      effector cell killing activities to hepatocarcinoma cells. DC pulsed with tumor
      antigen can induce higher specific CTL activity than unpulsed DC.

PMID- 11833079
TI  - Anti-HBV hairpin ribozyme-mediated cleavage of target RNA in vitro.
AB  - AIM: To study the preparation and cleavage activity of HpRz directed against the
      transcript of HBV core gene in vitro. METHODS: HpRz gene designed by computer
      targeting the transcript of HBV core gene was cloned into the vector p1.5 between
      5'-cis-Rz and 3'-cis-Rz. 32p-labeled HpRz transcript proved whether the vector
      fit for the preparation of hairpin ribozyme in vitro. 32p-labeled pKC transcript
      containing HBV core region as target-RNA was transcribed using T7 RNA polymerase
      and purified by denaturing PAGE. Cold HpRz transcript was incubated with 32p
      labeled target-RNAs under different conditions and radio autographed after
      denaturing polyacrylamide gel electrophoresis. RESULTS: HpRz has the specific
      ability of cleavage of target RNA at 37 degrees and 12 mM MgCl2. Km=26.31 nmol/L,
      Kcat=0.18/min. These results revealed that the design of HpRz was correct.
      CONCLUSION: HpRz prepared in this study possesses specific catalytic activity
      from the identification of cleavage activity. These results indicate that hairpin
      ribozyme may intracellularly inhibit the replication of HBV, therefore it may
      become a novel potent weapon for the treatment of hepatitis B.

PMID- 11833080
TI  - Seek protein which can interact with hepatitis B virus X protein from human liver
      cDNA library by yeast two-hybrid system.
AB  - AIM: To seek the X associated protein (XAP) with the constructed bait vector pAS2
      1X from normal human liver cDNA library. METHODS: The X region of the HBV gene
      was amplied by PCR and cloned into the eukaryotic expression vector pAS2-1. The
      reconstituted plasmid pAS2-1X was transformed into the yeast cells and the
      expression of X protein (pX) was confirmed by Western blot analysis. Yeast cells
      were cotransformed with pAS2-1X and the normal human liver cDNA library and were
      grown in selective SC/-trp-leu-his-ade medium, the second screen was performed
      with the LacZ report gene. Furthermore, segregation analysis and mating
      experiment were performed to eliminate the false positive and the true positive
      clones were selected for PCR and sequencing. RESULTS: Reconstituted plasmid pAS2
      1X including the anticipated fragment of X gene was proved by auto-sequencing
      assay. Western blot analysis showed that reconstituted plasmid pAS2-1X expressed
      BD:X fusion protein in yeast cells. Of 5 x 10(6) transformed colonies screened,65
      grew in the selective SC/-trp-leu-his-ade medium, 5 scored positive for beta-gal
      activity, and only 2 remaining clones passed through the segregation analysis and
      mating experiment. Sequence analysis identified that two clones contained similar
      cDNA fragment:GAACTTGCG. CONCLUSION: The short peptide(glutacid-leucine
      alanine)is a possible required site for XAP binding to pX. Normal human liver
      cDNA library has difficulties in expressing the integrated XAP on yeast cells.

PMID- 11833081
TI  - Expression and bioactivity identification of soluble MG7 scFv.
AB  - AIM: To examine the molecular mass and identify the bioactivity of MG7 scFv for
      its application as a targeting mediator in gene therapy of gastric cancer.
      METHODS: Two strongly positive recombinant phage clones screened from MG7
      recombinant phage antibody library were separately transfected into E.coli TG1.
      Plasmid was isolated from the transfected E.coli TG1 and digested by EcoR I and
      Hind III to examine the length of exogenous scFv gene. Then, the positive
      recombinant phage clones were individually transfected into E.coli HB2151. The
      transfectant was cultured and induced by IPTG. Perplasmic extracts was prepared
      from the induced transfectant by osmotic shock. ELISA was used to examine the
      antigen-binding affinity of the soluble MG7 scFv. Immunodotting assay was adopted
      to evaluate the yield of soluble MG7 scFv produced by transfected E.coli HB2151.
      Western blot was used to examine the molecular mass of MG7 scFv. Finally, the
      nucleotide sequence of MG7 scFv was examined by DNA sequencing. RESULTS: Two
      positive recombinant phage clones were found to contain the exogenous scFv gene.
      ELISA showed that MG7 scFv had strong antigen-binding affinity. Immuodotting
      assay showed that transfected E.coli HB2151 could successfully produce the
      soluble MG7 scFv with high yield via induction by IPTG. The molecular mass of MG7
      scFv was 30 kDa by western blot. DNA sequencing demonstrated that the VH and VL
      genes of MG7 scFv were 363 bp and 321 bp,respectively. CONCLUSION: We have
      successfully developed the soluble MG7 scFv which possessed strong antigen
      binding affinity.

PMID- 11833082
TI  - Direct effect of croton oil on intestinal epithelial cells and colonic smooth
      muscle cells.
AB  - AIM: To investigate the direct effect of croton oil (CO) on human intestinal
      epithelial cell (HIEC) and guinea pig colonic smooth muscle cells in vitro.
      METHODS: Growth curves of HIEC were drawn by MTT colorimetry. The dynamics of
      cell proliferation was analyzed with flow cytometry, and morphological changes
      were observed under light and electron microscopy after long-term (6 weeks)
      treatment with CO. Expression of cyclooxygenase-2 (COX-2) mRNA was detected by
      dot blot in HIEC treated with CO. Genes related to CO were screened by DD-PCR,
      and the direct effect of CO on the contractility of isolated guinea pig colonic
      smooth muscle cells was observed. RESULTS: High concentration (20-40 mg x L(-1))
      CO inhibited cell growth significantly (1, 3, 5, 7d OD sequence: (20 mg x L(-1))
      0.040+/-0.003, 0.081+/-0.012, 0.147+/-0.022,0.024+/-0.016; (40 mg x L(-1))
      0.033+/-0.044, 0.056+/-0.012, 0.104+/-0.010, 0.189+/-0.006; OD control 0.031+/
      0.008, 0.096+/-0.012, 0.173+/-0.009, 0.300+/-0.016, P<0.01), which appeared to be
      related directly to the dosage. Compared with the control, the fraction number of
      cells in G1 phase decreased from 0.60 to 0.58, while that in S phase increased
      from 0.30 to 0.34 and DNA index also increased after 6 weeks of treatment with CO
      (the dosage was increased gradually from 4 to 40 mg x L(-1)). Light microscopic
      observation revealed that cells had karyomegaly, less plasma and karyoplasm
      lopsidedness. Electron microscopy also showed an increase in cell proliferation
      and in the quantity of abnormal nuclei with pathologic mitosis. Expression of COX
      2 mRNA decreased significantly in HIEC treated with CO. Thirteen differential
      cDNA fragments were cloned from HIEC treated with CO, one of which was 100
      percent homologous with human mitochondrial cytochrome C oxidase subunit II. The
      length of isolated guinea pig colonic smooth muscle cells was significantly
      shortened after treatment with CO (P<0.05). CONCLUSION: At a high CO
      concentration (>20 mg x L(-1)), cell growth and proliferation are inhibited in a
      dosage-dependent manner. Increase in cell proliferation and in malignant
      conversion of the cellular phenotype is observed in cells cultured chronically
      with CO. COX-2 mRNA expression decreases significantly, while human mitochondrial
      cytochrome C oxidase subunit IImRNA expression increases significantly in HIEC
      treated with CO. CO also has a direct effect on the contractility of Guinea pig
      colonic smooth muscle cells.

PMID- 11833083
TI  - Identification of CD226 ligand on colo205 cell surface.
AB  - AIM: To confirm the existence of CD226 ligand and its distribution, which is a
      novel molecule cloned in 1996. METHODS: The mRNA was extracted from TPA activated
      Jurkat cells and used as a template for reverse-transcription. After PCR
      amplification, the fragment including CD226 extracellular region and the splice
      donor sequence "ACTTACCTGT" was obtained and cloned into fusion expression vector
      pIG. The recombinant vector pCD226/Ig was transfected in COS-7 cells by DEAE
      Dextran method, the secreting fusion protein was identified by Sandwich ELISA,
      and was purified by anti-CD226 affinity chromatography. This fusion protein was
      used as a probe in the investigation of CD226 ligand by immunohistochemistry.
      Existence of CD226 ligand was further identified by adhesion experiment. RESULTS:
      Expression of a secreting fusion protein was identified by sandwich
      ELISA,indicating that both CD226 extracellular domain and IgGFc domain could be
      recognized respectively by anti-CD226 and anti-hIgFc mAb. About 130g CD226/Ig
      fusion protein could be obtained from 100mL COS-7 culture supernatants by anti
      CD226 affinity chromatography purification. SDS-PAGE showed that this fusion
      protein has a molecular mass of 83ku. It was confirmed by immunohistochemistry
      that CD226 ligand expressed on the Colo205 cells, but not on Jurkat cell, U937
      cell and mixed lymphocyte culture cells. In adhesive assay, resting Jurkat cells
      did not have significant adhesion to Colo205 cells. In contrast, activated Jurkat
      cells could bind to colon carcinoma Colo205 cells and this adhesive reaction
      could be blocked by CD226/Ig fusion protein or anti-CD226 mAb. Immunochemical
      experiment showed that Colo205 cells could be specifically stained by CD226/Ig,
      indicating that CD226 ligand exists on the surface of Colo205 cells. CONCLUSION:
      Existence of CD226 ligand on the surface of Colo205 cells was identified by
      immunohistochemistry and adhesion blocking experiment. In addition, the secreting
      CD226/Ig fusion protein prepared in this study will be a potential tool for
      further investigation of CD226 ligand.

PMID- 11833085
TI  - Severe biliary complications after hepatic artery embolization.
AB  - AIM: To study the mechanism and treatment of severe biliary complications arising
      from hepatic artery embolization(HAE). METHODS: Of seven cases of intra- and
      extrahepatic biliary damage resulting from hepatic artery embolization reported
      since 1987, 6 patients suffered from hepatic haemangioma, the other case was due
      to injection of TH compound into the hepatic artery during operation. The hepatic
      artery was injected with ethanol so as to evaluate the liver damage in
      experimental rats. RESULTS: All the cases were found to have destructive damage
      of intra- and extrahepatic bile duct at the hilum with biliary hepatocirrhosis.
      Experimental results revealed necrosis of the liver parenchyma, especially around
      the portal tract and obliteration of intrahepatic bile duct. CONCLUSIONS: To
      prevent the severe biliary complications of HAE, the use of HAE for hepatic
      haemangioma which was widely practiced in China, should be re-evaluated. Hepatic
      arterial embolization of hepatic haemangioma may resulte in severe destructive
      biliary damages and its indiscriminate use should be prohibited.

PMID- 11833084
TI  - Effect of manganese on heat stress protein synthesis of new-born rats.
AB  - AIM: To study the effect of manganese (Mn) on heat stress protein 70 (HSP70)
      synthesis in the brain and liver of new-born rats whose mother-rats were exposed
      to Mn. METHODS: 32 female rats were randomly divided into four groups. One group
      was administrated with physiological saline only as control group, the other
      three groups were administrated with 7.5, 15 and 30 mg x kg(-1) manganese
      chloride (MnCl2) by intraperitioneal injection every two days for two weeks.
      After delivery, the mother-rats received MnCl2 unceasingly for a week with the
      same method. Then the contents of Mn Zn Cu and Fe in the livers of the new-born
      rats were determined by atomic absorption spectroscopy; The level of HSP70 in the
      brains and the livers of the new-born rats as detected by Western-dot-blotting,
      and the SOD activities were measured simultaneously. RESULTS: The contents of Mn
      in the livers of new-born rats of the experimental groups(respective 1.38+/-0.18,
      2.73+/-0.65,3.44+/-0.89 microg x g(-1)) were significantly increased compared
      with the control group(0.88+/-0.18 microg x g(-1); P<0.01); The contents of Fe in
      the livers of new-born rats of 15 and 30 mg x kg(-1) experimental groups (426+/
      125, 572+/-175 microg x g(-1), respectively) were significantly increased
      compared with the control group(286+/-42 microg x g(-1); P<0.05); the levels of
      Zn in the livers of the new-born rats of three experimental groups(254+/-49,
      263+/-47, 213+/-28 microg x g(-1), respectively) were lower than those of the
      control group(335+/-50 microg x g(-1); respective P<0.05, P<0.01); and the levels
      of Cu showed no significant difference among the four groups(three experimental
      groups: 75+/-21, 68+/-241 and 78+/-18 microg x g(-1); control group: 83+/-9
      microg x g(-1); P<0.05). There was a significant increase in the levels of HSP70
      in the brains of new-born rats of the 30 mg x kg(-1) group (19.5 x 10(3)+/- 1.3 x
      10(3)A;control group:14.3 x 10(3)+/-1.4 x 10(3)A; P<0.01) and the levels of HSP70
      in the livers of new-born rats of three experimental groups(respective 19.6 x
      10(3)+/- 3.9 x 10(3)A,18.5 x 10(3)+/-3.8 x 10(3)A, 22.4 x 10(3)+/-1.9 x 10(3)A)
      also increased than control group(13.3 x 10(3)+/-1.0 x 10(3)A;P<0.01), but the
      SOD activities showed no significant difference among brains of the four groups
      (experimental groups: 5.04+/-0.43, 4.83+/-0.48, 4.60+/-0.84 ku x g(-1); control
      group: 4.91+/-0.37 ku x g(-1); P<0.05). The SOD activities in the livers of 15 mg
      x kgP< group(5.41+/-0.44 ku x gP<) was lower than the control group(5.95+/-0.36
      ku x gP<; P<0.05). CONCLUSION: While mother-rats were exposed to manganese, the
      metabolisms of Mn Zn and Fe of new-born rats in the livers were influenced and
      were situated in a stress status, thus HSP70 syntheses is induced in the brains
      and livers of new-born rats, but the mechanism of this effect in the
      developmental toxicity of Mn remains to be further studied.

PMID- 11833086
TI  - Lipopolysaccharide induced synthesis of CD14 proteins and its gene expression in
      hepatocytes during endotoxemia.
AB  - AIM: To observe synthesis of CD14 protein and expression of CD14 mRNA in hepatic
      tissue and hepatocytes of rats during endotoxemia. METHODS: The endotoxemia model
      of Wistar rat was established by injection of a dose of lipopolysaccharide (LPS)
      (5mg x kg(-1), Escherichia coli O111:B4) via the tail vein, then the rats were
      sacrificed after 3, 6, 12 and 24 h in batches respectively. Hepatocytes were
      isolated from normal and LPS-injected rats by in situ collagenase perfusion
      technique and were collected to measure the expression of CD14 mRNA and synthesis
      of CD14 protein by reverse transcript-polymerase chain reaction (RT-PCR) or
      Western blot analysis. The binding of fluorescein isothiocyanate (FITC)-CD14
      polyclonal antibody to isolated hepatocytes was also assessed by flow cytometric
      analysis (FCM). RESULTS: In the rats with endotoxemia, the expressions of CD14
      mRNA in hepatic tissue and isolated hepatocytes were stronger at 3, 6, and 12 h
      than that in control rats (3.48+/-0.15, 5.89+/-0.62, 4.33+/-0.18, vs 1.35+/-0.14
      in hepatic tissue, P<0.01; 4.12+/-0.17, 6.24+/-0.64, 4.35+/-0.18, vs 1.87+/-0.15
      in hepatocytoes, P<0.01). The synthesis of CD14 protein in hepatic tissue and
      isolated hepatocytes increases also obviously in 6 and 12 h when compared to that
      in control rats (13.27+/-1.27, 17.32+/-1.35, 11.42+/-1.20, vs 7.34+/-0.72 in
      hepatic tissue, P<0.01; 14.68+/-1.30, 17.95+/-1.34,11.65+/-1.19, vs 7.91+/-0.70
      in hepatocytes, P<0.01). FCM showed that mean fluorescence intensity (MFI) and
      numbers of FITC-CD14 positive cells in the rats with endotoxemia increased
      obviously at 3,6,12 and 24h when compared with normal control group (43.4%,
      70.2%, 91.4%, 32.6% vs 4.5%, P<0.01). CONCLUSION: LPS can markedly promote the
      synthesis of CD14 protein and up-regulate the expression of CD14 mRNA in isolated
      hepatocytes and hepatic tissue. Liver might be a main source for soluble CD14
      production during endotoxemia.

PMID- 11833087
TI  - Multivariate regression analysis on early mortality after orthotopic liver
      transplantation.
AB  - AIM: To identify the risk factors relating to early mortality after orthotopic
      liver transplantation. METHODS: Clinical data of 37 adult patients undergoing
      liver transplantation were retrospectively collected and divided into two groups:
      the survived group and the death group (survival time<30 d). The relationship
      between multivariate risk factors and early mortality after orthotopic liver
      transplantation were analyzed by stepwise logistic regression. RESULTS: The
      survival rate was 73%. Early mortality rate was 27%. APACAE III, preoperative
      serum creatinine level and interoperative bleeding quantity had a significant
      independent association with early mortality. (R=0.1841, 0.2056 and 0.3738).
      CONCLUSION: APACHE III,preoperative serum creatinine level and interoperative
      bleeding quantity are significant risk factors relating to early mortality after
      orthotopic liver transplantation. To improve the recipient's preoperative
      critical condition and renal function and to reduce interoperative bleeding
      quantity could lower the early mortality after orthotopic liver transplantation.

PMID- 11833088
TI  - Relationship between cytokine mRNA expression and organ damage following cecal
      ligation and puncture.
AB  - AIM: To investigate the role of cytokine gene expression in organ damage at
      different tissue sites during sepsis. METHODS: Male NIH mice were subjected to
      cecal ligation and puncture (CLP) or sham operation (Sham). Pro-inflammatory
      cytokine (TNFalpha, IL-1beta and IL-6) and anti-inflammatory cytokine (IL-4) gene
      expression in the liver and lung tissue were assessed by RT-PCR. The permeability
      of microvascular and water content in the lungs and liver were also examined.
      RESULTS: Significant increase in TNFalpha, IL-1beta and IL-6 gene expression was
      observed at 3 and 12 h after CLP both in the liver and lungs (P<0.01).The level
      of IL-4 gene expression was not changed after CLP in the lungs, but increased at
      12 h after CLP(P<0.01) in the liver tissue. Both the liver and lungs showed a
      significant increase in microcirculatory permeability at 12 h after CLP(P<0.01),
      and the increase in the lungs was higher than that in the liver. The water mass
      fractions in the liver (P<0.05) and lungs (P<0.01) were increased after CLP, and
      the increase in the lungs happened earlier and more severely than that in the
      liver. CONCLUSION: The inflammatory response in the liver and lungs was different
      during sepsis. At the early stage of sepsis, pro-inflammatory reaction dominates
      both in the liver and lungs. But at the later stage of sepsis, induction of
      compensatory anti-inflammatory response was seen in the liver but not in the
      lungs. This difference in situ activity may contribute to the different
      vulnerability of organ damage during sepsis. The strategy of systemic
      administration of anti-inflammatory drugs to sepsis should be reconsidered.

PMID- 11833089
TI  - Construction of HCV-core gene vector and its expression in cholangiocarcinoma.
AB  - AIM: To establish an experimental model for exploring the role of hepatitis C
      virus (HCV) in the development of cholangiocarcinoma. METHODS: Recombinant
      plasmid of HCV-core gene was constructed with molecular cloning technique and
      transfected into QBC939 cells with lipofection.After it was selected with G418,
      resistant colonies were obtained. The colonies were analysed by
      immunocytochemistry and Western blotting. The morphology was observed under
      transmission electron microscope(TEM) and microscope. RESULTS: The recombinant
      plasmid was proved to carry the target gene by PCR and restriction enzymed
      mapping. Moreover, it could express HCV-C protein efficiently in QBC939 cells.
      The HCV-like particles were found in the cytoplasm by electron microscope, which
      were spherical with a diameter of 50 nm-80 nm possessing outer membrane. The
      transfected cells had lower differentiation and higher malignant degree under
      microscope. CONCLUSION: Because HCV-core gene could express steadily in
      cholangiocarcinoma cells,the transfected tumor cells(QBC939-HCVC) could be used
      to study the effect of HCV in the development of cholangiocarcinoma.

PMID- 11833090
TI  - CCK-8 inhibits expression of TNF-alpha in the spleen of endotoxic shock rats and
      signal transduction mechanism of p38 MAPK.
AB  - AIM: To study the effect of sulfated cholecystokinin-octapeptide (CCK-8) on
      systemic hypotension, gene and protein expression of TNF-alpha in the spleen of
      lipopolysaccharide (LPS)-induced endotoxic shock (ES) rats, and further
      investigate the signal transduction mechanism of p38 mitogen-activated protein
      kinase (MAPK). METHODS: The changes of blood pressure were observed using
      physiological record instrument in the four groups of rats: LPS (8 mg x kg(-1),
      iv), CCK-8 (40 microg x kg(-1), iv) pretreatment 10 min before LPS (8 mg x kg(
      1)), CCK-8 (40 microg x kg(-1), iv) or normal saline (control) group. The content
      of TNF-alpha in the spleen was assayed 2 h after LPS administration using ELISA
      kit and the expression of TNF-alpha mRNA was examined 30 min, 2 h and 6 h after
      LPS administration by reverse transcribed polymerase chain reaction (RT-PCR).
      Activation of p38 MAPK was detected with Western blot 30 min after LPS
      administration. RESULTS: CCK-8 reversed LPS-induced decrease of mean arterial
      pressure (MAP) in rats. The content of TNF-alpha in the spleen was (282+/-30) ng
      x L(-1) in control group, while it increased to (941+/-149) ng x L(-1) in LPS
      group, P<0.01. CCK-8 significantly inhibited the LPS-induced increase of TNF
      alpha content in spleen. It decreased to (462 +/-87) ng x L(-1) in CCK-8+LPS
      group, P<0.01. The expression of TNF-alpha mRNA 30 min and 2 h after treatment
      was stronger in LPS group, while it was lowered after CCK-8 pretreatment. The p38
      MAPK expression increased significantly in LPS group (5.84 times of control) and
      CCK-8 increased the activation of p38 MAPK in ES rats (10.74 times of control).
      CONCLUSION: CCK-8 reverses the decrease of MAP in ES rats and has inhibitory
      effect on the gene and protein expression of TNF-alpha in spleen, and p38 MAPK
      may be involved in its signal transduction mechanisms.

PMID- 11833091
TI  - Effect of cholesterol liposomes on calcium mobilization in muscle cells from the
      rabbit sphincter of Oddi.
AB  - AIM: To analyze the influence of cholesterol liposome on the Ca2+ mobilization of
      cultured muscle cells in the rabbit sphincter of Oddi's. METHODS: New Zealand
      rabbit was sacrificed and the sphincter of Oddi (SO) segment was obtained
      aseptically. The SO segment was cut into pieces and cultured in DMEM solution.
      Then the smooth muscle cells were subcultured, and the 4th-7th passage cells were
      used for further investigation. The intracellular Ca2+ increase was measured
      under confocal microscope after the addition of 20 mmol x L(-1) KCl, 10(-7) mol x
      L(-1) acetylcholine and 10(-7) mol x L(-1) cholecystokinin, and different
      antagonists were added to analyze the Ca2+ mobilization pathway. After the cells
      were incubated with 1g x L(-1) cholesterol liposome (CL)(molar ratio was -2:1),
      the intracellular Ca2+ increase was measured again to determine the effect of CL
      on cellular Ca(2+) mobilization. RESULTS: The resting cellular calcium
      concentration of cultured SO cell was 108+/-21 nmol x L(-1).The intracellular
      Ca2+ increases induced by 20 mmol x L(-1) KCl, 10(-7) mol x L(-1) ACh and 10(-7)
      mol x L(-1) CCK were 183+/-56% 161+/-52% and 130+/-43%, respectively. When the
      extracellular Ca2+ was eliminated by 2 mmol x L(-1) EGTA and 5 micromol x L(-1)
      verapamil, the intracellular Ca2+ increases induced by KCl, ACh and CCK were 20+/
      14%,82+/-21% and 104+/-23%, respectively. After the preincubation with heparin,
      the Ca2+ increases were 62+/-23% and 23+/-19% induced by ACh and CCK, as for
      preincubation with procaine they were 72+/-28% and 85+/-37% induced by ACh and
      CCK, respectively. Pretreatment with CL for 18 h, the resting cellular Ca2+
      concentration elevated to 152+/-26 nmol x L(-1), however, the cellular Ca2+
      increase percentages in response to these agonists were 67+/-32%,56+/-33% and
      34+/-15%. CONCLUSION: KCl elicit the SO cellular Ca2+ increase depends on influx
      of extracellular Ca2+, ACh evoked the SO cellular Ca2+ increase is through the
      mobilization of intracellular Ca2+ pool and influx of extracellular Ca2+ as well,
      CCK excites the SO cells mainly through mobilization of intracellular IP3
      sensitive Ca2+ store. After the incorporation with cholesterol liposome, KCl,ACh
      and CCK induced cellular Ca2+ increase percentages decreased.

PMID- 11833092
TI  - Early diagnosis and treatment of severe acute cholangitis.
AB  - AIM: To investigate the diagnostic standard for early identification of severe
      acute cholangitis in order to lower the incidence of morbidity and mortality
      rate. METHODS: A diagnostic standard was proposed in this study as
      follows:documented biliary duct obstruction by ultrasound or computerized
      tomography or other imaging tools with the manifestation of systemic inflammatory
      response syndrome (SIRS). The surgical procedures included emergency common bile
      duct exploration with T tube insertion or cholecystostomy with secondary common
      bile duct exploration. And incidence of postoperative multiple organ dysfunction
      syndrome (MODS), duration of systemic inflammatory response and hospital
      mortality were analyzed. RESULTS: Fourty-three patients conforming to the
      diagnostic standard described above were employed in this study. 1 patient was
      admitted in acutely ill condition and complicated with acute relapse of chronic
      bronchitis, cholecystostomy procedure was performed but the patient was
      complicated with postoperative acute lung injury which was treated by assisted
      mechanical ventilation for 5 d; 2 wk later, two-stage common bile duct
      Exploration and T tube insertion were performed. The remaining 42 patients
      underwent primary common bile duct exploration and T tube insertion, 1 developed
      acute lung injury and recovered 3 d later, 2 patients developed acute renal
      dysfunction, 1 of which recovered 2 d later and the other died on d 4. For all
      patients, the postoperative systemic inflammatory response persisted for 2 to 8 d
      with median of 3 d. CONCLUSION: Early diagnosis of severe acute cholangitis can
      be made using this diagnostic standard, further development of systemic
      inflammatory response could be prevented and incidence of MODS as well as
      hospital mortality decreased.

PMID- 11833094
TI  - An analysis of 10218 ulcerative colitis cases in China.
AB  - AIM: To analyze the characteristics of ulcerative colitis(UC) in China. METHODS:
      From 1981 to 2000, a total of 10218 patients of UC reported in Chinese medical
      literature and including our cases diagnosed were analyzed according to the
      diagnostic criteria of Lennard-Jones. RESULTS: The number of cases increased by
      3.08 times over the past 10 years (2506 patients were diagnosed from 1981 to 1990
      while 7512 patients were diagnosed from 1991 to 2000). Lesion range were
      described in 7966 patients, 5592 (70.20%) were proctosigmoiditis or proctitis,
      1792(22.50%) left-sided colitis, 582(7.30%) pancolitis. Among the 8122 patients,
      2826 (34.8%) had first episode, 4272 (52.6%) had chronic relapse, 869 (10.7%)
      were of chronic persist type, 154 (1.9%) were of acute fulminant type. The course
      of the illness were described in 5867 patients, 4427(75.5%) were less than 5
      years, 910 (15.5%) between 5 and 10 years,530 (9.1%) more than 10 years. Six
      hundred and sixteen patients 618 patients(6.1%) had extraintestinal
      manifestations. The mean age at the diagnosis was 40.7 years( range 6-80 years,
      and the peak ages 30-49 years). The male to female ratio was 1.09. Among 270
      patients diagnosed in our hospital,36 had histories of smoking, there was no
      negative association between the severity of UC and smoking(P>0.05), 21 smokers
      were followed up for one year, 15 of them had given up smoking when the disease
      were diagnosed, and one year later, 7 patients relapsed, another 6 patients
      continued smoking, and one year later,2 patients relapsed. Among 270 UC patients
      diagnosed in our hospital, 4 patients(1.48%) from 2 families had familial history
      of UC. Treatment was mentioned in 6859 patients, only 5-ASA and/or corticosteroid
      only in 1276 patients(18.6%), only Chinese herbs in 1377 patients(20.1%),
      combined Chinese and western medicine in 4056 patients(59.1%), surgery was
      performed in 87 patients(1.3%),other treatments in 63 patients(0.9%).
      CONCLUSIONS: In China, number of UC patients increased significantly in the past
      10 years. Lesions are commonly located to left side colon. The course is short
      with rare extraintestinal manifestations. The age of onset is relatively high.
      Males and females are nearly equally affected. No negative relation was found
      between smoking and severity of the disease. Familial relatives are rarely
      involved Traditional Chinese medicine(TCM) is widely used in the treatment of UC.

PMID- 11833093
TI  - Upregulation of vascular endothelial growth factor by hydrogen peroxide in human
      colon cancer.
AB  - AIM: To evaluate the effect of reactive oxygen species such as hydrogen peroxide
      on the progression of human colon cancer. METHODS: Human colon carcinoma cell
      lines, LS174T and HCT8, were treated respectively with 10(-5), 10(-7) or 10(-9)
      mol x L(-1) hydrogen peroxide for 24h,and co-cultured with human endothelial cell
      line ECV-304. The migration of ECV-304 induced by cancer cells was calculated and
      the expression level of vascular endothelial growth factor in cancer cells was
      determined by RT-PCR analysis and ELISA. Dactinomycin of 1.5mg x L(-1) which
      could block transcription of cancer cells was applied to observing the effects of
      H(2)O(2) on transcriptional activity and the relative half-life of VEGF mRNA.
      Finally,to evaluate the effect of H2O2 on NF-kappaB activity in colon cancer
      cells, NF-kappaB in cytoplasm and nucleus of the cells were detected with FITC
      tagged antibody and its presence in the nucleus(Fn) vs cytoplasm(Fc) was
      monitored by measuring the green fluorescence integrated over the nucleus by
      laser scanning cytometry(LSC). RESULTS: Exogenouse hydrogen peroxide of low
      concentration increased the migration of endothelial cell induced by colon cancer
      cells. When cancer cells were treated with 10(-5) mol x L(-1) H2O2, the migration
      number of endothelial cells induced by LS174T cells was 203+/-70 and the number
      induced by HCT8 cells was 145+/-65. The two values were significantly higher than
      those treated with other concentrations of H2O2 (P<0.01). The expression of
      vascular endothelial growth factor in cancer cells, which could be blocked by
      dactinomycin, were increased to a certain degree, while the relative half-life of
      VEGF mRNA was not prolonged after treatment with hydrogen peroxide. The activity
      of NF-kappaB in colon cells rose after the cells were exposed to hydrogen
      peroxide for 24h. The Fn values in HCT8 cells were 91+/-13 (0 mol x L(-1) H2O2)
      and 149+/-40(10(-5) mol x L(-1) H2O2)(P<0.05), in LS174T cells were 127+/-35(0
      mol x L(-1) H2O2) and 192+/-11(10(-5)mol x L(-1) H2O2) (P<0.05). It is similar to
      the case of VEGF expression in cancer cells. CONCLUSION: Hydrogen peroxide
      increases vascular endothelial growth factor expression in colon cancer cells,
      and it is likely that reactive oxygen species such as hydrogen peroxide
      facilitates the development of colon cancer.

PMID- 11833095
TI  - Screening and identification of proteins mediating senna induced gastrointestinal
      motility enhancement in mouse colon.
AB  - AIM: To isolate the proteins involved in pharmacologic action of senna extract
      (SE) from mouse gastrointestinal tract and to explore the molecular mechanism of
      gastrointestinal motility change induced by SE. METHODS: SE was administrated to
      mice by different routes. Gastrointestinal motility of mice was observed using
      cathartic, gastrointestinal propellant movement experiments and X-ray analysis.
      Mouse model for gastrointestinal motility enhancement was established through
      continuous gastric administration of SE at progressively increased dose. At 3 h
      and week 3, 4, 6 and 10, morphological changes of gastrointestinal tissues were
      found under light microscope. Ultrastructural changes of intestinal and colonic
      tissues at week 6 were observed under transmission electron microscope. The
      colonic proteomic changes in model mice were examined by two-dimension
      polyacrylamide gel electrophoresis with immobilized pH gradient isoelectric
      focusing to screen the differentially expressed proteins, and their molecular
      masses and isoelectric points were determined. Two N-terminal sequences of the
      samples were also determined by mass spectrometry. RESULTS: SE (0.3g) caused
      diarrhea after gastric administration in 1-6h and enhanced gastrointestinal
      propellant (65.1+/-7.5%; 45.8+/-14.6%, P<0.01) in mice, but intramuscular and
      hypodermic injection had no cathartic effect. X-ray analysis of gastrointestinal
      motility demonstrated that gastric administration of SE enhanced gastric
      evacuation and gastrointestinal transferring function. At 3 h and week 3 and 4
      after gastric administration of SE, light microscopic examination revealed no
      apparent change in gastrointestinal mucosal tissues, but transmission electron
      microscopic examination revealed inflammatory changes in whole layer of
      intestinal and colonic wall. Twenty differential proteins were detected in the
      colonic tissues of the model mice by two-dimensional electrophoresis, and the N
      terminal amino acid sequences of two proteins were determined. CONCLUSION: SE
      causes diarrhea and enhances gastrointestinal motility through digestive tract
      administration. Long-term gastric administration of SE induces inflammatory
      changes and cell damage in the whole gastrointestinal tract. The differential
      proteins screened from the colonic tissues of the model mice might mediate the
      enhancing effect of SE on gastrointestinal motility.

PMID- 11833097
TI  - Localization of neurokinin B receptor in mouse gastrointestinal tract.
AB  - AIM: To observe the location of neurokinin receptor (NK3r) in the mouse
      gastrointestinal tract. METHODS: The abdomens of 8 male Kunming mice were opened
      under anaesthesia with sodium pentobarbital. The exposed gut organs were kept
      moisture and temperature at the same time. Then the esophagus,jejulum, ileum, and
      colon, etc were respectively cut and the segments from the stomach to the distal
      colon were opened along the mesenteric border. A circular 4mm-6mm enteric
      part(pieces of 1 cm(2) were to be prepared) and mucosa and submucosa were
      removed, then the longitudinal muscle layer was pulled off from the circular
      muscle layer under microphotograph. They were rinsed in 50 nmol x L(-1) potassium
      phosphate-buffered saline(PBS). Immunohistochemistry and immunoreactive
      fluorescence were used in the staining procedures. RESULTS: There was NK3r-Like(
      Li) positive material on the smooth muscle cells of the esophagus, stomach, and
      intestines and other regions. The nerve cell bodies with immunoreactivity for
      NK3r were mainly distributed in the submucousal nerve plexus or myenteric nerve
      plexus of the gastrointestinal tract except for the esophagus, stomach and
      rectum. The reaction product was located on the surface of the nerve cell plasma.
      It was occasionally observed in the cell plasma endosomes, but was very weakly
      stained. Among the NK3-like positive neurons in the plexus,the morphological type
      in many neurons appeared like Dogiel II type cells. Some neuron cell bodies were
      big, having many profiles, some were long ones or having grading structure. Cell
      body diameter was about 10 microm-46 microm and 8 microm-42 microm in myenteric
      plexus and submucous plexus. CONCLUSION: This study not only described the
      distribution of neurokinin B receptor in the mouse gut, but also provided a
      morphological basis for deducing the functional identity of the NK3r-LI
      immunoreactivity neurons, suggesting the possibility that these neurons were
      closely related to gastrointestinal tract contraction and relaxing activity.

PMID- 11833096
TI  - Preventive effect of glutamine on intestinal barrier dysfunction induced by
      severe trauma.
AB  - AIM: To investigate the mechanism underlying intestinal barrier function damage
      after severe trauma and the therapeutic effect of glutamine. METHODS: Burned
      patients, and animal models of severe trauma replicated by hemorrhagic shock
      combined with endotoxin infusion and burn injury, were included in a serial
      experiment. Effects of oral glutamine on intestinal barrier function were
      observed in scalded rats. Parameters measured in these experiments were as
      follows: plasma levels of diamine oxidase (DAO), tumor necrosis factor
      (TNFalpha), endotoxin (LPS), and lactate as well as D-lactate by biochemical
      methods, lactose/mannitol (L/M) ratio in urine by SP-3400, and pathological
      examination of intestinal mucosa under light microscopy. RESULTS: Plasma DAO
      activity was significantly increased after injury. There was a negative
      correlation between plasma DAO and intestinal mucosal DAO or pHi (r=-0.93, plasma
      0.80+/-0.93,2.83+/-1.71, 1.14+/-0.64,2.36+/-2.06 and 2.49+/-1.67 vs intestinal
      0.52+/-0.12,0.34+/-0.03,0.45+/-0.18,0.37+/-0.26 and 0.41+/-0.07 r=-0.533, plasma
      0.87+/-0.75, 1.89+/-1.13,1.21+/-0.23,3.03+/-2.61 and 4.70+/-1.22 vs pHi 7.03+/
      0.05,7.05+/-0.06,7.14+/-0.096, 7.20+/-0.08 and 7.05+/-0.07 P<0.01-0.05). Positive
      correlations were found between DAO activity and plasma TNFalpha, LPS, lactate,
      L/M and D-lactate (r=0.817, 0.842, 0.872, and 0.951 plasma DAO 0.87+/-0.75,1.89+/
      1.13,1.21+/-0.23,3.03+/-2.61 and 4.70+/-1.22 vs TNF 0.08+/-0.02,0.03+/-0.25,
      0.17+/-0.09,0.34+/-0.15 and 0.33+/-0.18 vs LPS 0.14+/-0.03,0.16+/-0.04,0.21+/
      0.02,0.18+/-0.16 and 0.37+/-0.10 vs lactate 9.03+/-2.19,18.30+/-2.56, 9.81+/
      2.83,12.01+/-6.83,12.01+/-6.84 and 43.61+/-11.27 vs L/M 0.03+/-0.01,0.41+/
      0.27,0.62+/-0.20, 1.70+/-0.60 r=0.774, plasma DAO 1.25+/-0.41 2.17+/-0.71 2.29+/
      0.87 1.23+/-0.55 and 1.11+/-0.47 vs D-lactate 8.37+/-2.48,18.25+/-6.18, 13.96+/
      4.94,8.93+/-3.00 and 12.39+/-4.94 all P<0.01), respectively. Damage of intestinal
      mucosa was found by pathological examination. Intestinal barrier function was
      improved to a certain extent by oral glutamine in scalded rats. CONCLUSION:
      Intestinal barrier function was damaged in the early stage after trauma. Plasma
      DAO activity, D-lactate content, intestinal pHi and urine L/M may be sensitive
      markers of intestinal mechanical injury, and glutamine may protect against
      intestinal barrier dysfunction after severe trauma.

PMID- 11833098
TI  - Study on of bioadhesive property of carbomer 934 by a gamma camera in vivo.
AB  - AIM: To study the bioadhesive property of carbomer934 in dog alimentary tract.
      METHODS: Carbomer934 and ethylcellulose were radiolabelled with technetium-99m;
      and Gastrointestinal emptying rate of materials was measured using the technique
      of gamma scintigraphy. RESULTS: After oral administration,the maximum intestinal
      radioactivity of non-bioadhesive granules and bioadhesive granules were observed
      in the second hour and the sixth hour respectively. Constants of stomach emptying
      rate of nonadhesive granules,bioadhesive granules I and bioadhesive granules II
      were 0.774 h(-1), 0.265 h(-1) and 0.321 h(-1) respectively on the base of gastric
      residual amount. Compared to nonadhesive material (ethylcellulose), the migration
      rate of adhesive material(carbomer934) was remarkably slower in dog alimentary
      canal. CONCLUSION: It is concluded that, in the dog, interactions between
      gastrointestinal mucus layer and adhesive material or nonadhesive material were
      significantly different. Carbomer934 had stronger in vivo bioadhesive property
      than ethylcellulose.

PMID- 11833099
TI  - Gastric myoelectrical activity and gastric emptying in diabetic patients with
      dyspeptic symptoms.

PMID- 11833100
TI  - Proliferation of intestinal crypt cells by gastrin-induced ornithine
      decarboxylase.
AB  - AIM: To determine whether the gastrin stimulated intestinal crypt cell (IEC-6)
      proliferation by induction of ornithine decarboxylase (ODC). METHODS: IEC-6 cells
      were grown in DMEM containing 50 mL x L(-1) dialyzed fetal bovine serum for 24h
      and then were treated with gastrin. The proliferative capability of the cells was
      monitored subsequently on d 1, 2, 3, and 4 after treatment with MTT assay at
      aborbance 570 nm.The cellular ODC mRNA expression, ODC activity, and putrescine
      content were examined by RT-PCR method, radiometric technique and high
      performance liquid chromatography(HPLC) analysis respectively after 12h of
      treatment. RESULTS: On d1 after exposure of IEC-6 cells to pentagastrin, the
      proliferation increased initially and reached a peak on d3 at 250 microg x L(-1)
      concentration. Pentagastrin 500microg x L(-1) increased cell proliferation on day
      1 and day 2, and then decreased. Compared with control group, pentagastrin 250
      microg x L(-1) increased ODC mRNA level by 1.09-fold (P<0.05), ODC activity by
      1.71-fold(P<0.01), and putrescine content 5.30-fold (P<0.01), respectively.
      Similarly, pentagastrin of 500 microg x L(-1) also increased ODC mRNA level by
      1.16-fold (P<0.05), ODC activity 1.63-fold(P<0.05), and putrescine content 4.41
      fold (P<0.01), respectively. But there was not significant difference between
      them. CONCLUSION: Gastrin is an agent which promotes IEC-6 cell proliferation
      involved in regulating ODC activity mechanism.

PMID- 11833102
TI  - 'How do you find veins in people with very "fatty" arms or who seem to have very
      small (fragile) veins? Also, it is very hard to find cannulae narrower than
      20G.'.

PMID- 11833101
TI  - Study on the mechanism of regulation on the peritoneal lymphatic stomata with
      Chinese herbal medicine.
AB  - AIM: To study the mechanism of Chinese herbal medicine (CHM), the prescription
      consists of Radix Salviae Miltiorrhizae, Radix Codonopsitis Pilosulae, Rhizoma
      Atractylodis Alba and Rhizoma Alismatis, Leonurus Heterophyllus Sweet,etc on the
      regulation of the peritoneal lymphatic stomata and the ascites drainage. METHODS:
      The mouse model of live fibrosis was established with the application of
      intragastric installations of carbon tetrachloride once every three days;
      scanning electron microscope and computer image processing were used to detect
      the area and the distributive density of the peritoneal lymphatic stomata; and
      the concentrations and NO in the serum were measured and analyzed in the
      experiment. RESULTS: Two different doses of CHM could significantly increase the
      area of the peritoneal lymphatic stomata, promote its distributive density and
      enhance the drainage of urinary ion such as sodium, potassium and chlorine.
      Meanwhile, the NO concentration of two different doses of CHM groups was 133.52+/
      23.57 micromol/L and 137.2+/-26.79 micromol/L respectively. In comparison with
      the control group and model groups (48.36+/-6.83 micromol/L and 35.22+/-8.94
      micromol/L, P<0.01),there existed significantly marked difference, this made it
      clear that Chinese herbal medicine could induce high endogenous NO concentration.
      The effect of Chinese herbal medicine on the peritoneal lymphatic stomata and the
      drainage of urinary ion was altered by adding NO donor(sodium nitropurruside,SNP)
      or NO synthase (NOS) inhibitor (N(G)-monomethyl-L-arginine, L-NMMA) to the
      peritoneal cavity. CONCLUSION: There existed correlations between high NO
      concentration and enlargement of the peritoneal lymphatic stomata, which result
      in enhanced drainage of ascites. These data supported the hypothesis that Chinese
      herbal medicine could regulate the peritoneal lymphatic stomata by accelerating
      the synthesis and release of endogenous NO.

PMID- 11833103
TI  - Letter from the secretary.

PMID- 11833104
TI  - GDC new guidelines for general anaesthesia.

PMID- 11833105
TI  - SAAD annual conference. 31st October 1998. Royal Society of Medicine, London.

PMID- 11833106
TI  - Just another pretty face? Facial attractiveness and oral appearance in old age.

PMID- 11833107
TI  - Considerations for the use of oral sedation in the institutionalized geriatric
      patient during dental interventions: a review of the literature.
AB  - Some institutionalized elderly persons need a sedative prior to a dental
      examination or treatment because they have a disturbance due to physical
      illnesses, degenerative changes in the brain, and/or psychiatric disorders,
      associated with advanced aging. Oral administration is one of the safest methods
      of delivery of a sedative drug. It is almost universally acceptable, easy to
      administer, costs little, has a low incidence and severity of adverse reactions,
      and requires no additional formal specialized training for the dentist. However,
      theoretical and practical knowledge of sedation is essential. This paper reviews
      the literature on oral sedation for the geriatric patient. Benzodiazepines are
      most often used for oral sedation of geriatric patients. The properties of these
      drugs were reviewed, and recommendations were made with respect to the drugs of
      choice and their dosage. Generally, fast-acting benzodiazepines of short
      duration, with rapid rate of elimination and no active metabolites, are
      recommended. The drug of choice, and the dosage, may vary according to the
      medical history and physical condition of the patient.

PMID- 11833108
TI  - Oral health assessment by nursing staff of Alzheimer's patients in a long-term
      care facility.
AB  - Dental care and oral hygiene are often neglected in nursing homes. This study
      examines the effect of an education program on the ability of nursing staff to
      conduct an oral health assessment for a population of persons with Alzheimer's
      disease and related disorders. The findings of this study showed that the CNA's
      are as capable as the Licensed Nurses in assessing oral health status. In future
      training of nursing staff, increased emphasis on identification of problems in
      specific areas may improve the overall assessments by nurses and nursing
      assistants.

PMID- 11833109
TI  - Autoextraction in an autistic dental patient: a case report.
AB  - This is a case report of a 21-year-old male patient with autism who sought
      treatment at a General Practice Residency clinic for dental treatment following
      the autoextraction of several teeth. A review of autism and self-mutilation is
      presented.

PMID- 11833110
TI  - The accuracy of tooth loss data collected by nurses.
AB  - This paper reports on the accuracy of tooth counts conducted in 22 subjects by 10
      trained nurses as part of a large longitudinal study of a pharmacological agent.
      These nurses participated in a training course consisting of seminars,
      discussion, demonstrations, and practice examinations. Each of the nurses then
      counted the teeth of 22 subjects and recorded their findings independently. The
      counts of the nurses were compared with those of the dentists to assess the
      accuracy of the nurses' counts. We found that nurses and dentists were in perfect
      agreement for 86% of the patient counts conducted. Individual nurses' levels of
      agreement with dentists ranged from 73% to 100%, with pairwise kappa statistic
      values ranging from 0.70 to 1.00. In addition, both Pearson correlation and
      interclass correlation measures exceeded 0.98 for every comparison of dentist and
      nurse counts. The results of this study suggest that training nondental health
      care workers may be an accurate and low-cost way of obtaining tooth loss data and
      other oral health measures, particularly when oral health data are collected as
      part of larger, multi-disciplinary studies.

PMID- 11833111
TI  - Gastroenterological drugs and denture stomatitis.
AB  - The aim of this study was to investigate the medical and dental variables related
      to the presence of denture stomatitis. The study population was comprised of 106
      elderly people (82 women, 24 men; mean age, 81.3 years) using a maxillary
      complete denture and living in a geriatric nursing home in Oulu, Finland. The
      following variables were used in the analysis: medical diagnoses, which could
      have a possible biological association with stomatitis; daily use of drugs;
      ability to cope with everyday life; oral hygiene; and the condition of the
      denture. The prevalence of stomatitis was 52% among residents wearing complete
      dentures. Patients receiving gastroenterological drugs had less stomatitis (p =
      0.01, chi-square). The results suggest a preliminary finding that older adults
      using gastroenterological drugs had less stomatitis.

PMID- 11833113
TI  - The use of a neoprene "thumb-sock" to prevent trauma in a thumb-sucking child
      with intractable epilepsy.
AB  - A nine-year-old girl with spastic quadriplegia, mental retardation, poor vision,
      a gastrostomy, and intractable epilepsy was referred by her pediatrician for a
      dental assessment with a view to extracting her anterior teeth as a means of
      preventing repeated damage to the skin over the proximal phalanx of her left
      thumb, which she sucked at night. This was the time of day when the frequency of
      her epileptic seizures was highest. A simple solution to the problem was
      developed by a dentist and an occupational therapist in which nylon-coated 3-mm
      neoprene sheeting (wet-suit material) was formed into a "thumb-sock" with a
      simple Velcro fastening around the wrist. No trauma to the thumb from epileptic
      seizures has occurred since the "thumb-sock" was fitted 24 months ago.

PMID- 11833112
TI  - Facial attractiveness and the aged.
AB  - This study examined the relationship between dentofacial appearance and judgments
      of facial attractiveness in a sample of 60 subjects between ages 65 and 75.
      Subjects completed questionnaires regarding their current dental appearance and
      level of satisfaction with their facial attractiveness. Subjects then viewed and
      ranked four sets of five photographs that had been digitally manipulated to
      simulate common dental defects. Regardless of background facial attractiveness or
      gender of stimulus photographs, a specific ranking order for dental defects
      emerged with rank-order correlations in the 90% range. Findings suggest that
      dental appearance affects judgments of facial attractiveness regardless of gender
      or background facial attractiveness.

PMID- 11833114
TI  - GDC new guidelines for sedation.

PMID- 11833115
TI  - Association of Dental Anaesthetists winter meeting. 30th January 1999, King's
      College Hospital.

PMID- 11833117
TI  - Letter from the secretary.

PMID- 11833116
TI  - 'What is the panel's advice regarding emergency drug kits and resuscitation
      equipment for dental practices using sedation?'.

PMID- 11833118
TI  - Who should give sedation for out-patient dentistry and with what drugs?

PMID- 11833119
TI  - What drugs should be used for conscious sedation in out-patient dentistry?

PMID- 11833120
TI  - Topics in medicine: diabetes mellitus.

PMID- 11833121
TI  - Can we learn to beat the reaper? Science has been winning battles against old
      age, but can it win the war?

PMID- 11833122
TI  - A to Z guide to advances in medicine.

PMID- 11833123
TI  - Riding in cars with girls.

PMID- 11833124
TI  - Been down so long.... Prozac and other new drugs triggered a revolution in the
      treatment of depression. But do we still need the couch?

PMID- 11833126
TI  - Staying healthy. How to keep the doctor away.

PMID- 11833125
TI  - Despair beneath his wings. A troubled past may have led a teen to copy a suicide
      mission.

PMID- 11833127
TI  - Staying healthy. Vaccines stage a comeback.

PMID- 11833128
TI  - 10 foods that pack a wallop.

PMID- 11833130
TI  - Staying healthy. Preventive parenting.

PMID- 11833129
TI  - Staying healthy. Walk, don't run.

PMID- 11833131
TI  - Staying healthy. Too heavy, too young.

PMID- 11833132
TI  - Staying healthy. A public mess.

PMID- 11833133
TI  - Staying healthy. Playing chicken with our antibiotics. Overtreatment is creating
      dangerously resistent germs.

PMID- 11833134
TI  - Dental Sedation Teachers' Group. Meeting Tuesday, 18th May 1999. Guy's Dental
      Hospital.

PMID- 11833135
TI  - SAAD courses--now and the future.

PMID- 11833136
TI  - Pain and anxiety control in dentistry.

PMID- 11833137
TI  - An overview of risk assessment in sedation.
AB  - It is hoped that this article has raised some of the issues with regard to risk
      management in sedation; however, it does not replace the need to read the GDC
      Guidelines thoroughly and to ensure that sedation is practised in accordance with
      contemporary standards. When things do go wrong it is not unusual for Health
      Authorities or the GDC to take a very active interest and therefore early advice
      should always be sought from one's defence society.

PMID- 11833138
TI  - Loss of the right to administer general anaesthesia.

PMID- 11833139
TI  - Diabetes mellitus. What progress is being made toward a personal/daily use
      monitor.

PMID- 11833140
TI  - Undergraduate sedation teaching.

PMID- 11833141
TI  - Seminar on the teaching of pain and anxiety control.

PMID- 11833142
TI  - Improving tolerability of immunosuppressive regimens.
AB  - CNIs and corticosteroids are associated with adverse effects that can diminish
      quality of life and detrimentally affect long-term allograft and patient
      survival. Nephrotoxicity is the major side effect of CNI therapy. A search has
      been ongoing for improved immunosuppressive regimens that will provide adequate
      protection against acute allograft rejection, while decreasing the nephrotoxic
      and other effects associated with CNIs. This paper reviewed the immunosuppressive
      agent sirolimus as a potential new option in transplantation, focusing on its
      mechanism of action and clinical efficacy as well as potential antiproliferative
      and antineoplastic properties. The findings and lessons learned from key clinical
      studies in which sirolimus was used to augment or replace CNIs and/or
      corticosteroids were highlighted, and the importance of clinical pharmacokinetics
      and therapeutic drug monitoring in these regimens were discussed. Preliminary
      studies of combination therapy with sirolimus and tacrolimus in solid organ
      transplantation indicate that sirolimus/tacrolimus combination therapy may
      provide strong protection against acute rejection and diminish the nephrotoxicity
      associated with CNI-based therapy. Other studies suggest that sirolimus can be
      used as base immunosuppressive therapy, thereby completely avoiding the
      nephrotoxicity associated with CNI-based therapies, while continuing to provide
      powerful protection against rejection. With patients surviving longer with
      functional allografts, quality of life is becoming an increasing important
      clinical endpoint in transplantation. The studies reviewed here suggest that
      sirolimus might be used to improve quality of life significantly without
      increasing the risk of allograft rejection or shortening patient survival.

PMID- 11833143
TI  - Redefining expectations in transplantation: minimizing side effects, maximizing
      quality of life. Introduction.

PMID- 11833144
TI  - Improving quality of life--the new target for transplantation.
AB  - The incidence of ESRD continues to increase, particularly in older populations,
      and is associated with considerable comorbidity and a diminished QOL. Renal
      replacement therapy has been shown to improve QOL in patients with ESRD, and
      renal transplantation appears to produce greater improvements in QOL than
      dialysis. In the years since the first transplantations, the techniques have
      progressed from experimental to a practical approach to the treatment of end
      stage solid organ failure. Substantial advances that have improved both short
      term and long-term patient and graft survival have led to a heightened awareness
      of the need to examine the long-term QOL in transplant recipients. Recent trends
      show that patients are less concerned with short-term outcomes, such as whether a
      renal allograft will be lost, and more concerned with anxieties about long-term
      kidney function and overall health. Side effects associated with
      immunosuppression in transplantation can impact QOL negatively. The availability
      of newer immunosuppressants offers the possibility that these agents might be
      used to improve efficacy and decrease side effects associated with traditional
      agents, thereby improving QOL. However, healthcare systems will also insist that
      therapeutic regimens be cost-effective. Much work remains to evaluate new
      immunosuppressive regimens, although limited early results suggest sirolimus is a
      promising agent.

PMID- 11833145
TI  - Steroid side effects and their impact on transplantation outcome.
AB  - Steroids are a staple of immunosuppressive therapy in transplantation. Despite
      the high incidence of side effects associated with steroid therapy, the risk of
      increased rejection with steroid discontinuation has often outweighed the
      potential benefits of improved quality of life. With the advent of a number of
      newer immunosuppressive agents, however, there has been a renewed and heightened
      focus on the possibility of steroid avoidance or withdrawal protocols that do not
      place the patient or graft at undue risk. Much of the work in this area is
      preliminary, and large long-term trials are needed to reach definitive
      conclusions. Clinical trials need to resolve patient selection criteria for
      steroid discontinuation, effective and appropriate baseline immunosuppression,
      and the optimal timing of steroid withdrawal. Appropriate monitoring parameters
      also need to be developed to reduce the risk of acute rejection, and follow-up of
      patients who have been withdrawn from steroids will become increasingly
      important. Nonetheless, the hope is that newer immunosuppressive agents will soon
      allow for a reduction in steroid use in appropriate patients, with an improvement
      in patients' long-term quality of life, and fewer healthcare-related costs.

PMID- 11833146
TI  - Assessing cardiovascular risk profile of immunosuppressive agents.

PMID- 11833147
TI  - Controlling the incidence of infection and malignancy by modifying
      immunosuppression.
AB  - Long-term outcomes in renal transplantation have improved over the years but are
      still a matter of concern. Because patients typically require lifelong
      immunosuppression, the risks of cancer and infection associated with
      immunosuppressive agents continue to demand attention. Physicians strive
      endlessly to find the right balance between the level of immunosuppression
      required to prevent rejection and the level that will minimize dose-dependent
      side effects. Data presented in this paper suggest that some renal transplant
      recipients might have more than necessary immunosuppression during maintenance
      therapy and that reducing the immunosuppressant dose can decrease cancer
      incidence, without worsening long-term patient or allograft survival.
      Additionally, data were examined suggesting that immunosuppressive agents might
      be associated with different risks for cancer, specifically, the potential
      advantage of reduced cancer risk for sirolimus and sirolimus derivatives in
      comparison with standard immunosuppressive agents. Although promising, these
      preliminary results are from preclinical studies, and further study is warranted.

PMID- 11833148
TI  - Clinical audit and long-term evaluation of renal transplant recipients.
AB  - Renal transplant recipients now have an increased life expectancy, and this has
      highlighted the need for increased concern about the long-term complications
      associated with transplantation. To better manage renal transplant recipients
      over the long term, it is essential to schedule periodic clinic visits to detect
      problems and intervene in a timely fashion. Besides enabling early detection and
      possible treatment, periodic visits permit continuing patient education.
      Unfortunately, there is no scientifically based consensus that indicates what the
      optimal frequency and timing of such visits should be, although the AST has
      recently issued some guidelines. At the MINT, an Annual Review Clinic has been
      implemented to provide better service to renal transplant recipients over the
      long term. The clinic offers a comprehensive medical assessment, identifies and
      quantifies risk factors for CVD, and initiates referrals to appropriate
      specialists. The Annual Review Clinic increases patient awareness in a number of
      areas specific to transplantation, promotes a positive approach to healthcare,
      enables collection of structured data for analysis, and, with hope, engenders a
      significant degree of patient well-being and satisfaction. The medical community
      needs to continue long-term patient evaluation and clinical audit as means to
      improve long-term patient and graft survival, as well as patient quality of life.

PMID- 11833149
TI  - New strategies to reduce nephrotoxicity.
AB  - Since the introduction of cyclosporine, CNIs have formed the basis of
      immunosuppressive therapy in renal transplantation. The propensity of these
      agents to ultimately damage the very organs they were intended to protect was
      always recognized, but largely ignored due to their impressive ability to improve
      short-term outcomes. With the availability of equally powerful new
      immunosuppressive agents devoid of major nephrotoxicity, the irony of this
      situation has become all too apparent, and investigators are beginning to
      reevaluate the role of CNIs in renal transplantation. In this paper, we looked at
      strategies using MMF or sirolimus to reduce, withdraw, or replace CNIs in renal
      transplantation. Although MMF has proved effective in combination with CNIs,
      particularly in reducing acute rejection rates, its use as base therapy to allow
      CNI therapy to be withdrawn or eliminated is questionable. On the basis of
      initial trials, sirolimus holds promise for use as base therapy. To date, it is
      probably the only agent used in renal transplantation that provides
      immunosuppression comparable to cyclosporine or tacrolimus, which may someday
      allow sirolimus to replace. CNIs or allow early withdrawal of CNI therapy.
      Further study is needed to better clarify the role of sirolimus in improving long
      term renal transplantation outcomes.

PMID- 11833150
TI  - An ethical analysis of the mandatory exclusion of immigrants who test HIV
      positive.
AB  - On 20 September 2000, Canadian newspapers reported that Health Canada recommended
      to Citizenship and Immigration Canada (CIC) that testing all prospective
      immigrants for HIV, and excluding those testing positive, constitutes "the lowest
      health risk course of action." Subsequently, the Minister of Citizenship and
      Immigration stated that CIC is indeed considering implementing mandatory HIV
      testing for all prospective immigrants to Canada, and excluding all those testing
      positive (with the exception of refugees and family-class sponsored immigrants)
      from immigrating to Canada on both public health and "excessive cost" grounds.
      This proposal was met with vehement opposition from a broad range of
      organizations and individuals. In particular, they pointed out that, as stated in
      the International Guidelines on HIV/AIDS and Human Rights (UNHCHR/UNAIDS, 1998:
      para 105), "[t]here is no public health rationale for restricting liberty of
      movement or choice of residence on the ground of HIV status." At the time of
      going to print, no final decision had been made about whether mandatory HIV
      testing for all immigrants would be implemented. There are sound ethical, legal,
      and public policy arguments against imposing mandatory testing and excluding
      those who test HIV-positive.

PMID- 11833151
TI  - Access to treatment as a right to life and health.
AB  - In some countries in Latin America, in the absence of leadership from
      governments, activists have had to resort to the courts to obtain access to
      HIV/AIDS treatments for people with HIV/AIDS. In his presentation to the XIII
      International AIDS Conference (abstract TuOrE458), Edgar Carrasco, of Accion
      Ciudadana Contra el Sida (ACCSI), discusses the process that was followed in
      Venezuela. The presentation describes the very limited access people with
      HIV/AIDS had to antiretroviral therapies and treatments for opportunistic
      infections under Venezuela's health and social security systems. It provides
      details of lawsuits that were launched on behalf of several individuals living
      with HIV/AIDS, and that resulted in the courts ordering the government to provide
      treatments for these individuals and, eventually, for all people with HIV/AIDS in
      Venezuela. The presentation concludes that recourse to the courts is a useful
      tool for activists and that civil actions launched on behalf of people with
      HIV/AIDS can serve as an example for people with other chronic diseases.

PMID- 11833152
TI  - A human rights critique of the United Kingdom's HIV response.
AB  - The National AIDS Trust (NAT) is the United Kingdom's leading HIV policy and
      advocacy NGO. NAT is committed to promoting a human rights framework for HIV
      responses through work with communities, governments, professionals, and the
      private sector, both within the UK and internationally. In this presentation to
      the XIII International AIDS Conference (abstract WeOrE524), John Godwin and Saul
      Walker discuss current human rights issues related to HIV/AIDS in the UK, and
      NAT's perspective on the International Guidelines on HIV/AIDS and Human Rights as
      an advocacy tool.

PMID- 11833153
TI  - Panel recommends significant changes to federal law against discrimination.
AB  - In a report released on 23 June 2000, the Review Panel tasked by the federal
      Minister of Justice with reviewing the Canadian Human Rights Act made some
      welcome recommendations for improving the Act and the way the Canadian Human
      Rights Commission functions. Three are of particular significance: the
      recommendation that "social condition" be added to the prohibited grounds for
      discrimination listed in the Act; the recommendation that the Canadian Human
      Rights Commission should have, under its governing legislation, the duty to
      monitor and report to Parliament and the UN Human Rights Committee on the federal
      government's compliance with international human rights treaties regarding
      economic, social, and cultural rights; and the recommendation that "gender
      identity" should be expressly added to the Act as a prohibited ground of
      discrimination.

PMID- 11833154
TI  - Victory for transgendered people in gaining protection against discrimination.
AB  - On 7 June 2000, the BC Supreme Court rejected an attempt by the Vancouver Rape
      Relief Society to prevent the provincial human rights commission from hearing a
      complaint that it had discriminated against a transgendered woman. Kimberly Nixon
      filed a complaint with the BC Human Rights Commission in August 1995, alleging
      that the Vancouver Rape Relief Society had refused to allow her to work as a
      volunteer counselor because she had not been biologically female at birth.

PMID- 11833155
TI  - Federal law recognizes same-sex "common-law partners".
AB  - On 31 July 2000, legislation enacted by Parliament to amend 68 different federal
      statutes so as to recognize gay and lesbian common-law couples as having the same
      rights and obligations as heterosexual common-law couples came into force.

PMID- 11833156
TI  - Hiding children to avoid ARV treatment.
AB  - In the last issue, we reported on the case of a Montreal woman with HIV who lost
      custody of her two HIV-positive children after refusing to consent to their
      treatment with antiretroviral therapy.

PMID- 11833157
TI  - Ontario adopts policy on discrimination based on gender identity.
AB  - On 30 March 2000, as a follow-up to a discussion/consultation paper on gender
      identity, the Ontario Human Rights Commission approved a "Policy on
      Discrimination and Harassment because of Gender Identity."

PMID- 11833158
TI  - Needle exchange programs in prisons in Spain.
AB  - On 11 July 2000, at the XIII International AIDS Conference in Durban, yet another
      country--Spain--presented evidence that needle exchange programs in prisons work.
      We reproduce here the text of the presentation entitled "Needle Exchange Program
      at the Bilbao Prison, Spain: Two Years of Experience (1997-1999)."

PMID- 11833159
TI  - Criminal law and HIV/AIDS: update IV.
AB  - This regular column reviews new developments in the area of criminal prosecutions
      for HIV transmission or exposure, or developments that have come to our attention
      since the last issue. Canadian developments are the focus. Cases and legislation
      from other jurisdictions are only included if they represent a significant
      development in this area of the law or for the jurisdiction in question.

PMID- 11833160
TI  - Canada loses appeal of WTO panel ruling on minimum patent terms.
AB  - In the last issue, we reported on a ruling of a Panel of the World Trade
      Organization (WTO) that Canada was in breach of the international Agreement on
      Trade-Related Aspects of Intellectual Property Rights (the TRIPS Agreement). The
      Panel found that Canada's Patent Act does not provide the minimum patent terms
      required by the trade agreement. Canada appealed that decision, but on 18
      September 2000 the WTO Appellate Body upheld the Panel ruling.

PMID- 11833161
TI  - Canada ordered to implement WTO ruling against "stockpiling" of generic drugs.
AB  - In the last issue, we reported on a mixed World Trade Organization (WTO) ruling
      regarding Canada's patent laws, based on a complaint by the member states of the
      European Communities (joined by the United States). In March 2000, a WTO Panel
      accepted the provision in Canada's Patent Act that creates an "early working
      exception" to patent rights--in other words, that allows a third party to use a
      patented invention during the term of patent protection, as long as the use is
      for obtaining regulatory approval of an equivalent product to be sold once the
      patent expires. This was an important victory from the perspective of allowing
      earlier access to generic versions of patented drugs.

PMID- 11833162
TI  - US files WTO complaints against Brazil over requirement for "local working" of
      patents.
AB  - At the end of May 2000, the US (later joined by the European Communities) filed a
      complaint against Brazil at the World Trade Organization (WTO), alleging Brazil
      was in violation of its obligations under the Agreement on Trade-Related Aspects
      of Intellectual Property Rights (the TRIPS Agreement) and the 1994 General
      Agreement on Tariffs and Trade. Brazilian legislation that came into force in
      1997 establishes that, in order to enjoy exclusive patent rights in Brazil, the
      holder of a patent on an invention must satisfy a "local working" requirement. In
      other words, the patent holder must "work" the patent in Brazil to enjoy full
      patent protection. If it fails to do this, the law says it shall be subject to
      the possibility of the government issuing a compulsory license, allowing someone
      else to use the invention and pay a royalty fee to the patent holder.

PMID- 11833163
TI  - Canada files WTO complaint against EC.
AB  - In December 1998, Canada filed a complaint alleging that the European Communities
      (EC) had adopted regulations that amounted to a scheme to extend patent terms,
      limited to pharmaceutical and agricultural chemical products.

PMID- 11833165
TI  - The XIII International AIDS Conference, held this summer in Durban, South Africa.

PMID- 11833164
TI  - Complaint against Argentina over protection of patents and test data.
AB  - On 30 May 2000, the same day as the complaint against Brazil, the US (again
      joined by the EC) filed a complaint against Argentina, alleging that its patent
      laws violate the TRIPS Agreement in a number of ways.

PMID- 11833166
TI  - Namibia: refusal to enlist HIV-positive in army ruled discriminatory.
AB  - On 10 May 2000, in N v Minister of Defence, the Labour Court in Windhoek
      delivered a mixed ruling on HIV-based discrimination in employment that could
      have significant positive implications for armies throughout the region of
      southern Africa.

PMID- 11833167
TI  - Ecuador: police force HIV testing on detained transvestites.
AB  - In September 2000, Amnesty International reported that nine transvestite sex
      workers were detained by police in Guayaquil, Ecuador on 5 July 2000 for over
      three weeks on charges of crimes against decency and violating "public morals."
      AI believes they were detained solely because of their identity as transvestites,
      and notes that these are not isolated cases.

PMID- 11833168
TI  - News from Venezuela.
AB  - A Venezuelan court has ordered a university to stop requiring HIV testing for
      admission, while shortly thereafter the Venezuelan Ministry of Health and Social
      Development authorized obligatory HIV screening of pregnant women.

PMID- 11833169
TI  - South Africa: airline found guilty of employment discrimination.
AB  - On 28 September 2000, the Constitutional Court of South Africa ruled that South
      African Airways (SAA) violated the constitutional rights of Jacques Hoffmann in
      September 1996 by refusing to employ him as a cabin attendant on the ground that
      he is HIV-positive.

PMID- 11833170
TI  - HIV/AIDS legal issues in the United States.
AB  - The HIV/AIDS epidemic continues to be a leading public health issue in the United
      States. During the past decade, the epidemic has shifted away from the gay
      community, although gay and bisexual men continue to be the largest single HIV
      exposure category. Now, HIV increasingly affects low-income people of colour in
      urban areas, as well as women. As AIDS becomes more and more a minority, inner
      city disease, public focus on the epidemic as a significant social and political
      issue is waning. While a full survey of current issues in US law is beyond the
      scope of this article, the focus here is on current issues that are highly
      relevant to the direction the epidemic appears to be taking.

PMID- 11833171
TI  - Red Cross and federal government held liable for hemophiliacs' HIV infection.
AB  - After eight years of litigation, on 21 June 2000 three hemophiliacs infected with
      HIV finally won a judgment against the Canadian Red Cross Society and the federal
      government. An Ontario trial court ruled the Red Cross and the government were
      negligent for having delayed the implementation of heat treatment for blood
      products, which resulted in the plaintiffs' infections. Since starting their
      lawsuits in 1992, two of the three plaintiffs died of AIDS before the trial
      judgment. But the damage awards were criticized by the plaintiffs' lawyer.

PMID- 11833172
TI  - Draft discussion paper on HIV/AIDS and immigration released.
AB  - In October 2000, the Canadian HIV/AIDS Legal Network released a 57-page draft
      discussion paper on HIV/AIDS and immigration, reacting to the announcement that
      HIV testing may become mandatory for all prospective immigrants to Canada. A
      final version of the paper will be released in early 2001.

PMID- 11833174
TI  - Putting third first: opening statement.

PMID- 11833173
TI  - Putting third first: critical legal issues and HIV/AIDS.
AB  - On 7 July 2000, before the XIII International AIDS Conference, the Canadian
      HIV/AIDS Legal Network and the AIDS Law Project, South Africa held a one-day
      satellite meeting on legal, ethical, and human rights issues in Durban, South
      Africa. Entitled Putting Third First--Critical Legal Issues and HIV/AIDS, the
      satellite focused on legal strategies to advance the human rights of those most
      vulnerable to HIV/AIDS and to discrimination: people in the developing world, and
      people who, although they live in the industrialized world, suffer from poverty
      and marginalization and are at high risk of contracting HIV. The satellite grew
      out of the ongoing partnership between the Canadian HIV/AIDS Legal Network and
      the AIDS Law Project, South Africa, and was co-hosted by UNAIDS.

PMID- 11833175
TI  - Resolving legal, ethical, and human rights challenges in HIV vaccine research.
AB  - In the absence of a cure for AIDS, attention has turned to the possibility of
      developing a preventive vaccine for HIV infection. Yet many scientific, ethical,
      legal, and economic obstacles remain. At the current rate, the development and
      production of an effective vaccine could take 15 to 20 years or longer. If tens
      of millions more HIV infections and deaths are to be avoided in the coming
      decades, vaccine research needs to be greatly expedited. Furthermore, it must be
      undertaken ethically, and the products of this research must benefit people in
      developing countries. This article, an edited and updated version of a paper
      presented at "Putting Third First," addresses challenges arising in HIV
      preventive vaccine research in developing countries. It does not address clinical
      research in developing countries relating to treatments or therapeutic vaccines.
      Nor does it address legal and ethical issues relating to HIV vaccine research in
      industrialized countries, although similar issues arise in both contexts. The
      article concludes that while ethical codes are silent on the obligation to
      undertake research and development, international law provides strong legal
      obligations--particularly with regard to industrialized states--that should be
      invoked to accelerate HIV vaccine development, and distribution.

PMID- 11833176
TI  - Criminal law and HIV/AIDS: strategic considerations.
AB  - Richard Elliott's paper on criminal law and HIV/AIDS, an edited and updated
      version of his presentation at "Putting Third First," sets out five guiding
      principles for criminal law policy and HIV/AIDS; briefly outlines the rationales
      for criminalization; discusses three strategic legal questions regarding the
      criminalization of HIV transmission/exposure; and offers a number of
      recommendations for consideration of those needing to articulate a well
      considered perspective on the ethical, legal, human rights, and public health
      dimensions of the criminalization of HIV transmission/exposure.

PMID- 11833177
TI  - Using rights and the law to reduce women's vulnerability to HIV.
AB  - Cathi Albertyn's paper, an edited and updated version of her presentation at
      "Putting Third First," argues that both human rights and the law can play an
      important, if limited, role within a wider set of national and international
      strategies to reduce women's vulnerability to HIV. It analyzes the nature of
      women's vulnerability to HIV/AIDS, and highlights some of the issues and lessons
      in using rights and the law to advance gender equality and reduce women's
      vulnerability to HIV/AIDS.

PMID- 11833178
TI  - The deafening silence of AIDS.
AB  - For most of those attending the XIII International AIDS Conference in Durban, the
      Jonathan Mann Memorial Lecture delivered by Justice Edwin Cameron on Monday, 10
      July 2000, was one of the highlights of the conference. The presentation is a
      passionate and compelling appeal to make medical care and treatment accessible
      and affordable to the more than 30 million people in resource-poor countries who
      face death from AIDS.

PMID- 11833179
TI  - Court approves final Red Cross bankruptcy plan to compensate blood victims.
AB  - Following two years of negotiations, the insolvent Canadian Red Cross Society
      received court approval on 14 September 2000 of its plan to compensate victims of
      Canada's tainted blood tragedy (and pay other creditors).

PMID- 11833180
TI  - Gender, sexuality, and HIV/AIDS: the what, the why, and the how.
AB  - The focus of Geeta Rao Gupta's plenary presentation of 12 July 2000 at the XIII
      International AIDS Conference is on the what, why, and how of gender, sexuality,
      and HIV/AIDS. Dr Rao Gupta discusses the factors associated with women's
      vulnerability to HIV; and the ways in which unequal power balance in gender
      relations increases not only women's, but also men's, vulnerability to HIV
      despite, or rather because of, their greater power. She then addresses the
      question of how one is to overcome the seemingly insurmountable barriers of
      gender and sexual inequality. How can we change the cultural norms that create
      damaging, even fatal, gender disparities and roles? According to Dr Rao Gupta, an
      important first step is to recognize, understand, and publicly discuss the ways
      in which the power imbalance in gender and sexuality fuels the epidemic. She
      provides examples of sensitive, transformative, and empowering approaches to
      gender and sexuality and concludes that, in the final analysis, reducing the
      imbalance in power between women and men requires policies that are designed to
      empower women--policies that aim to decrease the gender gap in education, improve
      women's access to economic resources, increase women's political participation,
      and protect women from violence.

PMID- 11833181
TI  - Supreme court to hear appeal in negligence claim against Red Cross for HIV
      infection.

PMID- 11833182
TI  - Recent court rulings on medical and non-medical marijuana.
AB  - The last several months saw important victories but also disappointments in
      litigation over criminal prohibitions of marijuana in Canada. Four cases are
      summarized below--two deal with claims regarding medical marijuana, the other two
      with recreational use.

PMID- 11833183
TI  - Human rights and the AIDS crisis: the debate over resources.
AB  - In his plenary presentation of 11 July 2000 at the XIII International AIDS
      Conference, Kenneth Roth, the Executive Director of Human Rights Watch, the
      largest US-based human rights organization, reflects on whether a human-rights
      perspective can help us confront the AIDS crisis. More specifically, he asks the
      question whether human rights can help us meet the urgent challenge of securing
      the vast resources we need for treatment and prevention. Mr Roth believes they
      can. He argues that human rights are a powerful tool for meeting basic human
      needs, but that their contribution to the fight against AIDS is not as simple or
      straightforward as many often assume. In his presentation, he explains why.

PMID- 11833184
TI  - Revising the declaration of Helsinki: ethics vs economics or the fallacy of
      urgency.
AB  - Constant vigilance is required to ensure that the rights of volunteers in
      clinical trials are protected, particularly in developing countries. In this
      presentation to the XIII International AIDS Conference (abstract ThOrE651),
      Dirceu B Greco, of the Federal University of Minas Gerais in Brazil, describes
      the debate that has raged over the proposed changes to the Declaration of
      Helsinki, particularly with respect to access to medical care for trial
      volunteers and to the use of placebos in the control arms of the trials. The
      presentation argues: (1) that all trial volunteers should have access to the best
      diagnostic, preventive, and therapeutic methods, regardless of the standard of
      care in the countries where the trials are taking place; (2) that large efficacy
      trials of vaccines and drugs should be done first in countries where the best
      diagnostic, preventive, and therapeutic methods are available; and (3) that the
      costs of providing care and prevention services should be considered an integral
      part of the cost of the trials. The presentation explains how a partnership
      between activists, scientists, ethicists, and medical associations was effective
      in resisting pressures to lower the ethical standards for clinic trials. The
      presentation concludes that the gains made by this partnership constitute an
      important step in the struggle to provide universal access to education and
      health.

PMID- 11833185
TI  - Supreme Court rules on disability discrimination.
AB  - On 3 May 2000, the Supreme Court of Canada released a unanimous decision
      involving the interpretation of the term "handicap" in Quebec's anti
      discrimination legislation in three complaints filed with the province's human
      rights commission. While none of the cases involved HIV-related discrimination,
      the Court's strong decision is of definite benefit in protecting and promoting
      the rights of people with HIV/AIDS, particularly for those living in Quebec. The
      decision recognizes that people are protected against discrimination based on
      disability even if their condition does not give rise to any functional
      limitation and the discrimination is based on the perception that they are
      disabled.

PMID- 11833186
TI  - Man with HIV gets reprieve from deportation.
AB  - On 4 November 1999, the Federal Court (Trial Division) lifted a "removal order"
      just hours before a man with AIDS was to be deported to El Salvador, his country
      of origin.

PMID- 11833187
TI  - Discrimination in employment alleged.
AB  - In April 2000, former stockbroker DeWolf Shaw filed a $340-million civil suit in
      the Quebec Superior Court against First Marathon Inc.

PMID- 11833188
TI  - Federal court of appeal strikes claim for extending patent term.
AB  - In a short October 1999 decision, Pfizer Inc v Canada, the Federal Court of
      Appeal affirmed a lower court decision that Canadian law currently provides only
      17 years protection for drug patents filed before October 1989, and that the 20
      year minimum period stated in intellectual property treaties negotiated under the
      auspices of the World Trade Organization have not (yet) taken effect in Canada
      with respect to these drugs.

PMID- 11833189
TI  - HIV vaccine: ethics and human rights.
AB  - The ethical dilemmas of vaccine development are particularly acute with respect
      to HIV because of the nature of the virus itself and the social setting of
      prejudice and stigma in which the virus operates, argues Justice Michael Kirby in
      an article first printed in the [Australian] National AIDS Bulletin, reprinted
      here with permission.

PMID- 11833190
TI  - New guidelines on ethical considerations in HIV preventive vaccine research.
AB  - In March 2000, UNAIDS released annotated guidance points on the ethical
      considerations of HIV vaccine research (the "Guidance Document"). The guidance
      points, reproduced at the end of the article, are the product of two years'
      consultation and debate around the world, yet key questions remain unsettled.
      This article reviews the process, the outcomes, and the challenges that remain.

PMID- 11833191
TI  - Reform MP proposes compulsory testing.
AB  - In October 1999, a Reform Party Member of Parliament introduced Bill C-244 (the
      Blood Samples Act) in the House of Commons as a private member's bill. The bill
      proposes to permit forced blood testing of persons for HIV or hepatitis B or C
      where peace officers, firefighters, and other emergency services personnel or
      other health-care workers, may have been exposed to the risk of infection. It
      also proposes imprisonment for up to six months of any person who refuses court
      ordered testing. In January 2000, the Canadian HIV/AIDS Legal Network wrote to
      the federal Minister of Justice, explaining why such legislation is unnecessary,
      unethical, contrary to existing law regarding "informed consent," and
      unconstitutional. On 21 March 2000, the Bill passed second reading unanimously.
      It now awaits committee hearings. This article sets out the concerns the Network
      raised about the proposal for compulsory HIV testing.

PMID- 11833192
TI  - Rapid HIV screening at the point of care: legal and ethical issues.
AB  - In March 2000, the Canadian HIV/AIDS Legal Network released a comprehensive
      report entitled Rapid HIV Screening at the Point of Care: Legal and Ethical
      Issues. The release of the report coincided with the issuing of the first license
      to sell rapid HIV test kits in Canada for use by health-care professionals at the
      "point of care," and received considerable media attention. The report makes 23
      recommendations to federal and provincial/territorial health officials, health
      care professionals and their professional associations and regulatory bodies, and
      test kit manufacturers, with a view to ensuring that the potential benefits of
      this testing technology are maximized and the potential harms are prevented or
      minimized. We reproduce here the executive summary of the report.

PMID- 11833193
TI  - Supreme Court of Canada has just released an important decision.

PMID- 11833194
TI  - Criminal law and HIV/AIDS: update III.
AB  - This regular column reviews new developments in the area of criminal prosecutions
      for HIV transmission or exposure, or developments that have come to our attention
      since the last issue of the Newsletter. Canadian developments are the focus.
      Cases and legislation from other jurisdictions are only included if they
      represent a significant development in this area of the law or for the
      jurisdiction in question.

PMID- 11833195
TI  - Mixed WTO ruling on generic drug development.
AB  - On 17 March 2000, the World Trade Organization upheld the provision in Canada's
      patent laws that allows generic drug manufacturers to develop (but not sell)
      their cheaper versions of patented medicines before the 20-year patients expire.
      The decision prevents pharmaceutical companies from enjoying market monopolies
      beyond their patent terms, avoiding what would otherwise be even lengthier delays
      in the sale of cheaper, generic drugs in Canada. This decision is of significance
      not only to Canada, but also to other WTO member countries and to all individuals
      who use pharmaceutical products. However, the decision is not all positive: the
      WTO also ruled that Canada is violating international agreements by letting
      generic manufacturers stockpile their versions of patented drugs before patents
      expire. This article explains the issues, the arguments, and the decision.

PMID- 11833196
TI  - Panel rules against Canada on patent terms for pre-TRIPS patents.
AB  - On 5 May 2000, the WTO Panel issued another ruling regarding patents of relevance
      to pharmaceutical products. Upholding a complaint by the US, the Panel ruled that
      Canada's Patent Act was in breach of the minimum patent terms for inventions
      required by the Agreement on Trade-Related Aspects of Intellectual Property
      Rights (the TRIPS Agreement).

PMID- 11833197
TI  - US Supreme Court allows limits on AIDS-related insurance benefits.
AB  - In a ruling issued on 10 January 2000 with respect to Doe v Mutual of Omaha
      Insurance, the US Supreme Court refused to review a lower-court decision allowing
      an insurance company to limit health-care benefits for AIDS-related claims to
      less than one-tenth of what it pays under the same policies for expenses related
      to other illnesses. The lower court had ruled that anti-discrimination
      legislation does not apply to insurance policies.

PMID- 11833198
TI  - The BC persons with AIDS Society Advocacy Department.
AB  - This is the fourth in a series of articles about specialized legal and advocacy
      services for people with HIV/AIDS. In previous issues of the Newsletter, Ruth
      Carey provided an overview of the work of the HIV & AIDS Legal Clinic, Ontario
      (HALCO), Johanne Leroux described the work of the legal clinic of the Quebec
      Committee for people with HIV in Montreal, and Jennifer Duff described the work
      of the HIV Legal Services division of the Ottawa Clinic. In this article, Tarel
      Quandt, Director of Individual Advocacy, describes the work of the Advocacy
      Department of the British Columbia Persons with AIDS Society (BCPWA).

PMID- 11833199
TI  - HIV/AIDS, human rights, and development.
AB  - In just two decades, AIDS has become the leading cause of death in Africa, and
      now kills more people worldwide than any other infectious disease. Although
      current treatments are expensive, and an affordable vaccine in the developing
      world is many years away, HIV/AIDS prevention programs and activities often
      remain narrow in their scope, applicability, and impact. A human rights approach
      to the HIV/AIDS epidemic moves beyond a focus on the individual to address
      social, economic, and political factors that drive the epidemic, such as gender
      based inequalities, poverty, corruption, and government inaction. A rights-based
      approach empowers affected individuals and communities, and challenges
      governments to justify their actions (or inaction) to the people they represent
      and, ultimately, to the global community. We reproduce a fact sheet written by
      David Patterson for the Interagency Coalition on AIDS and Development (ICAD). It
      sets out a rights-based approach to development, examines the human rights
      dimensions of the HIV/AIDS pandemic, and gives examples of right-based
      programming in the context of the developing world. It concludes with sources of
      further information, both in hard copy and on the web.

PMID- 11833200
TI  - Medical treatment of children with HIV/AIDS.
AB  - In the last issue of the Newsletter, we reported on the case of a Montreal woman
      who sought an injunction from the Quebec Superior Court to prevent physicians
      from administering antiretroviral medication to her HIV-positive sons, of whom
      she had previously lost custody because of her refusal to consent to such
      medication. In December 1999, the Court of Quebec (Youth Division) heard the
      mother's application to regain custody and an application by the Director of
      Youth Protection for an order declaring that the children were in need of
      protection, as well as an order that the children be placed in the physical
      custody of another family for a period of two years, that the authority to make
      decisions regarding the children's medical care be removed from the mother and
      placed with the Director of Youth Protection, and that the children receive the
      necessary medications and diet. The Court issued its decision on 12 January 2000.

PMID- 11833201
TI  - HIV-related discrimination in New Brunswick increasing.
AB  - In February 2000, AIDS New Brunswick, AIDS Saint John, and SIDA AIDS Moncton
      released findings of a study on the needs of people with HIV/AIDS in New
      Brunswick.

PMID- 11833202
TI  - Canadian senate committee to review drug laws and policies.
AB  - Canada's Senate voted on 11 April 2000 to establish a Special Committee to
      conduct a comprehensive review of Canadian drug laws and policies.

PMID- 11833203
TI  - Evaluation of needle exchange pilot projects shows positive results.
AB  - We first reported on a needle-distribution pilot project undertaken in two
      prisons in Lower Saxony, a state in Northern Germany, in 1997. Scientific
      evaluation of the project has now shown what scientific evaluation of such
      projects in Switzerland had also shown--that needle exchange programs can be
      successfully implemented in prisons.

PMID- 11833204
TI  - HIV/AIDS in prisons: more new developments.
AB  - Since our last review, there have been new developments in several jurisdictions
      in the area of HIV/AIDS and prisons. This column reviews some important
      developments in Canada and in the US: the results of the evaluation of HIV/AIDS
      harm-reduction measures in the Canadian federal prison system; another Canadian
      inmate's fight for methadone maintenance treatment in prison; an important
      article on health care in Canadian prisons which states that there is little
      evidence that the federal prison system "is making any serious effort to provide
      treatment to any drug users"; the US Supreme Court's refusal to review a lower
      court's ruling permitting Alabama prisons to segregate HIV-positive inmates; an
      important ruling stating that inmates are entitled to receive medications in jail
      without interruption; and research showing that women inmates in the US are 23
      times more likely to have AIDS than women in the general population.

PMID- 11833205
TI  - Surveillance and prevention of hepatitis C in Australian prisons.
AB  - Hepatitis C (HCV) prevalence rates in prisons are even higher than HIV prevalence
      rates. Studies undertaken in the early and mid 1990s in Canadian prisons revealed
      rates of between 28 and 40 percent, and rates continue to rise. In one federal
      prison, 33 percent of study participants tested positive in 1998, compared to
      27.9 percent in 1995; and at the Burnaby Correctional Centre for Women in British
      Columbia, over 78 percent of 69 inmates tested for HCV between 1 January 1996 and
      8 August 1996 were seropositive. Similar figures are reported from other
      countries, including Australia. This raises many challenges for prison systems:
      how best to provide care and treatment to HCV-positive inmates; and how to
      prevent the further spread of HCV. Most HCV-positive inmates come to prison
      already infected, but the potential for further spread is high: HCV is much more
      easily transmitted than HIV, and transmission has been documented in prisons in
      several countries, including Canada. In Australia, an action plan for the
      surveillance and prevention of HCV in prisons has been developed as a result of
      meetings held in 1998 and 1999. We reproduce here the executive summary of the
      plan.

PMID- 11833206
TI  - Court rejects appeal for safe supply of medical marijuana.
AB  - As previously reported, in a May 1999 decision in Wakeford v Canada, the Ontario
      Superior Court of Justice granted an HIV-positive man an "interim constitutional
      exemption" from the provisions in the Controlled Drugs and Substances Act that
      make it an offence to possess or to produce or cultivate marijuana.

PMID- 11833207
TI  - HIV/AIDS and legal issues in Australia.
AB  - In Australia, a "blueprint" for HIV and AIDS-related law reform was produced in
      the early 1990s, but progress in achieving reform has been uneven. In 2000,
      discrimination against people with HIV/AIDS continues, and there are new threats
      to some of the very measures that are responsible for Australia's remarkable
      success in fighting the HIV/AIDS epidemic among injection drug users. This
      article, by Chris Ward, a member of the Legal Working Group of the Australian
      National Council on AIDS, Hepatitis C and Related Diseases, provides an overview
      of the law reforms achieved in Australia, and of current and future challenges.
      It concludes that the overarching challenge Australia faces in promoting an
      enabling legal environment is the waning impetus for reform, at a time when
      substantial areas of legislation and practice still warrant attention.

PMID- 11833208
TI  - Switzerland, the law, and HIV: an overview.
AB  - From the first appearance of HIV/AIDS in Switzerland in the mid 1980s, various
      legal tools have been implemented to combat the disease, most of them based on
      legislation already in force. To date, there has been no specific AIDS-related
      legislation, but if the formal legal framework has changed very little, practice
      has developed and demonstrates the extent to which the law reflects current
      societal values. At the risk of "giving the game away," it must be said at the
      outset that there are virtually no major HIV/AIDS-related legal problems in
      Switzerland.

PMID- 11833209
TI  - Appeals heard on both medical and non-medical marijuana.
AB  - In October 1999, the Ontario Court of Appeal heard an appeal in the case of R v
      Parker. Terry Parker was charged in 1996, after a police raid on his home in
      which the marijuana plants he was growing to ensure a supply in order to control
      his epileptic seizures were confiscated.

PMID- 11833210
TI  - HIV/AIDS and legal issues in England and Wales.
AB  - In England and Wales, the only HIV specialist legal advice service is currently
      observing "a return of many of the problems that were encountered in the 1980s
      but which we thought had been resolved." Ignorance about HIV and about how HIV is
      (and is not) transmitted continues, while the many benefits from new treatments
      have been accompanied by complacency, misunderstanding, and new forms of
      discrimination. This article, by members of the Advice Centre of the Terrence
      Higgins Trust, which includes the HIV specialist legal advice service, provides
      an overview of some of the legal issues currently facing people with HIV/AIDS in
      the UK, from discrimination to the rights of HIV-positive parents and their
      children, from housing to immigration and criminal law.

PMID- 11833211
TI  - India--workshops on "HIV/AIDS: the law and ethics".
AB  - The Lawyers Collective HIV/AIDS Unit is a non-governmental organization providing
      legal aid, advice, and support to people with HIV/AIDS in India. This article
      summarizes a series of workshops on "HIV/AIDS: The Law and Ethics" organized by
      the Unit to empower people with HIV/AIDS and educate the Indian judiciary.

PMID- 11833212
TI  - BC appellate court dismisses insurance appeal.
AB  - As reported in the last issue of the Newsletter, in September 1997 a British
      Columbia trial court had dismissed a "wrongful dismissal" claim by the estate of
      a gay man who died of AIDS against his former employer for damages arising out of
      his termination, including the loss of his life insurance coverage. The man's
      estate appealed that decision to the BC Court of Appeal. The Canadian AIDS
      Society and the BC Persons with AIDS Society were denied leave to intervene
      before the appellate court to make submissions. The case was heard in October
      1999 by the British Columbia Court of Appeal. In December 1999, the Court
      released its judgment dismissing the appeal.

PMID- 11833213
TI  - Global AIDS fund board to develop plan of action at first official meeting.

PMID- 11833214
TI  - Funding for AIDS programs to rise as Congress OKs spending bills.

PMID- 11833215
TI  - Jury to decide if suit was timely against blood-products firms.

PMID- 11833216
TI  - Court: HIV-positive hygienist a health threat to dental patients.

PMID- 11833217
TI  - Discrimination. State cannot prevent bias suit with retroactive legislation.

PMID- 11833218
TI  - Report: U.S. faces 'AIDS fatigue' in third decade of epidemic.

PMID- 11833220
TI  - WHO: investment in health care offers economic benefits.

PMID- 11833219
TI  - Indifference claim against jailers lacked sufficient evidence.

PMID- 11833221
TI  - Appeals court ruling upholds damages for AIDS defamation.

PMID- 11833222
TI  - Physical injury not needed to claim distress damages.

PMID- 11833223
TI  - Victimization of man with AIDS adds to harassment penalty.

PMID- 11833224
TI  - Tennessee high court restores $4.3 million damage award.

PMID- 11833225
TI  - Court allows needlestick product-liability case to proceed.

PMID- 11833226
TI  - Nurse wins disability benefits for incorrect HIV-test report.

PMID- 11833228
TI  - HIV status revealed in court, but not grounds for appeal.

PMID- 11833227
TI  - Southwestern Bell employee loses bid to make bias claim.

PMID- 11833229
TI  - Understanding the keys to effective case management training.

PMID- 11833230
TI  - Hospital improves joint replacement discharges.

PMID- 11833231
TI  - Technologies save case managers time and money.

PMID- 11833232
TI  - Knock the wind out of asthma with Asthma CareWay.

PMID- 11833233
TI  - Reader questions: audits motivate documentation. What have you done to improve
      documentation of patient education?

PMID- 11833234
TI  - OIG sounds alarm on transfer coding errors.

PMID- 11833235
TI  - Nebraska healthcare system successfully rebrands. Alegent pledges higher standard
      of care.
AB  - Omaha, Neb.-based Alegent Health launched a rebranding effort during its fifth
      anniversary. Seeking an improved the growth rate, the campaign changed its
      general health and wellness position to one which stressed its high standard of
      patient care and its commitment to the community. Part of the campaign's success
      is attributed to its consistent use, and its incorporation into all Alegent
      collateral and public relations efforts. The 2000 Alegent Health Annual Report
      also reinforced the new position.

PMID- 11833236
TI  - Popular honorees, classic appeal contribute to fund raising success. UPHC
      leadership dinner grows every year.
AB  - University of Pittsburgh Cancer Institute ran its ninth annual Leadership Dinner
      with record-high results: $522,115. Every year, invitations use a traditional
      design incorporating the university's venerable 1787 logo. The event receives a
      boost from an internal awards event for hospital staffers, held the day prior to
      the dinner. In the two past years, the dinner was recognized by the Pittsburgh
      Post-Gazette as the "Best Awards Dinner" in the area.

PMID- 11833237
TI  - Refreshing campaign aims to revive rehab referrals. Staten Island University
      Hospital reinforces rehab credentials.
AB  - Staten Island University Hospital, Staten Island, N.Y., runs a campaign to
      REinforce its REcognition as an excellent Rehabilitiation center. Radio and print
      ads reach a large community, while a direct mail campaign targets hospital social
      workers and discharge personnel with fun-loving, RElated gifts.

PMID- 11833238
TI  - Affinity program raises awareness of Greenwich hospital geriatric center.
AB  - In Greenwich, Conn., Greenwich Hospital uses an affinity program called
      GENERATIONS to help market its Geriatric Health and Resource Center. The program
      has attracted 4,000 members since opening in October 1999. They are drawn to an
      array of discount offers, frequent educational programs, and sponsored trips and
      activities.

PMID- 11833239
TI  - Concord, N.H., hospital cited for significant progress using Internet. Web site
      builds connections with a variety of constituents.
AB  - Concord Hospital, Concord, N.H., is one of the nation's "10 Most Improved
      Hospitals," based on its significant progress in using Internet technologies. The
      Hospital's Web site, www.concordhospital.org., has received other awards.

PMID- 11833240
TI  - North Carolina hospital redefines itself as critical-access facility. Bertie
      Memorial called a national model.
AB  - Bertie Memorial Hospital. Windsor, N.C., is redefining itself in its new home as
      a national model for critical-access hospitals designated by the federal Office
      of Rural Health Policy. The hospital recently opened a new $10 million, 48,000
      square-foot, state-of-the-art facility.

PMID- 11833241
TI  - New names add vitality to Florida, Pennsylvania healthcare providers. University
      Community Health, Guthrie Health unveil new logos.
AB  - This article examines two projects which included new names and logos. University
      Community Health, St. Petersburg, Fla., is the combination of University
      Community Hospital and University Community Hospital-Carrollwood, in Tampa, with
      Sun Coast Hospital and Helen Ellis Memorial Hospital, St. Petersburg, Fla.
      Guthrie Health, Sayre, Pa., is the new not-for-profit corporation formed by
      Guthrie Healthcare System and Guthrie Clinic, Sayre, Pa. Denver-based Monigle
      Associates spearheaded both branding campaigns.

PMID- 11833242
TI  - Balance assessment in patients with peripheral arthritis: applicability and
      reliability of some clinical assessments.
AB  - BACKGROUND AND PURPOSE: Many individuals with peripheral arthritis blame
      decreased balance as a reason for limiting their physical activity. It is
      therefore important to assess and improve their balance. The purpose of the
      present study was to evaluate the applicability and the reliability of some
      clinical balance assessment methods for people with arthritis and various degrees
      of disability. METHOD: To examine the applicability and reliability of balance
      tests, 65, 19 and 22 patients, respectively, with peripheral arthritis
      participated in sub-studies investigating the applicability, inter-rater
      reliability and test-retest stability of the following methods: walking on a soft
      surface, walking backwards, walking in a figure-of-eight, the balance sub-scale
      of the Index of Muscle Function (IMF), the Timed Up and Go (TUG) test and the
      Berg balance scale. RESULTS: For patients with moderate disability walking in a
      figure-of-eight was found to be the most discriminative test, whereas ceiling
      effects were found for the Berg balance scale. Patients with severe disability
      were generally able to perform the TUG test and the Berg Balance Scale without
      ceiling effects. Inter-rater reliability was moderate to high and test-retest
      stability was satisfactory for all methods assessed. CONCLUSIONS: Applicable and
      reliable assessment methods of clinical balance were identified for individuals
      with moderate and severe disability, whereas more discriminative tests need to be
      developed for those with limited disability.

PMID- 11833243
TI  - Reliability of measurement of angular movements of the pelvis and lumbar spine
      during treadmill walking.
AB  - BACKGROUND AND PURPOSE: Angular movements of the pelvis and lumbar spine are
      thought to play an important role in walking. However, little is known about the
      amount of unpredictable variability in measurement of these movements during
      human walking. The aim of the present study was to determine the retest
      reliability of measuring the angular movements of the pelvis and lumbar spine
      during unimpaired familiarized treadmill walking. METHOD: Retest reliability for
      26 subjects without pathology was determined over a one-week interval. Subjects
      walked on a treadmill at self-selected or a slower speed while measurements of
      the three-dimensional angular movements were taken with a computer-based video
      analysis system. RESULTS: The frontal plane movements of pelvic list and lumbar
      lateral flexion (relative to the pelvis) could be measured with high retest
      reliability at both self-selected and slow walking speeds (intraclass coefficient
      (ICC) (2, 1) > or = 0.81). In contrast, transverse and sagittal plane movements
      demonstrated moderate reliability at both speeds (0.37 < or = ICC (2, 1) < or =
      0.76). Averaging the measurement over six strides resulted in increased observed
      reliability (self-selected walking speed summary Pearson's r = 0.71, slow walking
      speed summary Pearson's r = 0.79) compared to taking the measurement based on a
      single stride (self-selected walking speed summary Pearson's r = 0.63, slow
      walking speed summary Pearson's r = 0.67). Unlike pelvic and lumbar movements
      (relative to the pelvis), the measurement of lumbar movements (relative to the
      global reference frame) appeared to depend on whether subjects were walking at
      self-selected or slow speeds. CONCLUSIONS: Measurement of pelvic list and lumbar
      lateral flexion (relative to the pelvis) could be applied with confidence to
      hypothesis testing about individuals or groups. Movements in the transverse and
      sagittal planes are unlikely to be appropriate in hypothesis testing about
      individuals and hence clinical practice, but may still have experimental
      applications in hypothesis testing about groups.

PMID- 11833244
TI  - Cervicocephalic kinaesthesia: reliability of a new test approach.
AB  - BACKGROUND AND PURPOSE: Relocating either the natural head posture (NHP) or
      predetermined points in range are clinical tests of impaired neck proprioception
      but memory might influence these tests. Three new tests, reasoned to be more
      challenging for the proprioceptive system, were developed. The objectives were to
      assess the reliability of all tests and whether the three new tests were more
      challenging for the proprioceptive system. METHOD: A test-retest design was used
      to assess the reproducibility and errors of all five tests. Twenty asymptomatic
      volunteers were assessed a week apart, using an electromagnetic movement sensor
      system, the 3-Space Fastrak. A measure of error magnitude was used to detect
      kinaesthetic sensibility. Comparison of the means and their corresponding
      dispersion were analysed descriptively. The between-day intraclass correlation
      coefficients (ICCs) were calculated and plots of mean differences between days 1
      and 2 were conducted to estimate test reliability. Multivariate analysis of
      variance (MANOVA) and least significant difference (LSD) pairwise comparisons
      were performed to compare the test accuracy between different target positions.
      RESULTS: ICCs were between 0.35 and 0.9, but plotting the data modified the
      interpretation in some tests. Relocating a NHP was easier when the trunk was in a
      neutral position than when pre-rotated (error 2.46 degrees (+/- 0.2 degree)
      versus 5.95 degrees (+/- 0.7 degree). Relocating a 30 degrees rotation position
      (error 5.8 degrees (+/- 0.6 degree) and repeatedly moving through a target (error
      4.82 degrees (+/- 0.7 degree) was also difficult. CONCLUSIONS: The new tests were
      more challenging than relocating the NHP but the reliability of tests relocating
      uncommon positions was questionable.

PMID- 11833245
TI  - A randomized controlled trial comparing periodic mask CPAP with physiotherapy
      after abdominal surgery.
AB  - BACKGROUND AND PURPOSE: Physiotherapists use a variety of techniques aimed at
      improving lung volumes and secretion clearance in patients after surgery.
      Periodic continuous positive airway pressure (PCPAP) is used to treat patients
      following elective upper abdominal surgery. However, the optimal method of
      application has not been identified, more specifically, the dosage of application
      of PCPAP. The present randomized controlled trial compared the effects of two
      dosages of PCPAP application and 'traditional' physiotherapy upon functional
      residual capacity (FRC), vital capacity (VC), oxyhaemoglobin saturation (SpO2),
      incidence of post-operative pulmonary complications and length of stay with a
      control group receiving 'traditional' physiotherapy only. METHOD: Fifty-seven
      subjects were randomly allocated to one of three groups. All groups received
      'traditional' physiotherapy twice daily for a minimum of three post-operative
      days. In addition, two groups received PCPAP for 15 or 30 minutes, four times per
      day, for three days. RESULTS: Fifty subjects (39 male; 11 female) completed the
      study. There were no significant differences in any variables between the three
      groups. The overall incidence of post-operative pulmonary complications was 22%
      in the control group, 11% and 6% in the PCPAP 15-minute and PCPAP 30-minute
      groups, respectively. Length of hospital stay was not significantly different
      between the groups but for subjects who developed post-operative pulmonary
      complications, the length of stay was significantly greater (Z = -2.32; p =
      0.021). CONCLUSIONS: The addition of PCPAP to a traditional physiotherapy post
      operative treatment regimen after upper abdominal surgery did not significantly
      affect physiological or clinical outcomes.

PMID- 11833248
TI  - Onwards and upwards.

PMID- 11833247
TI  - Fusion not feuding.

PMID- 11833246
TI  - Relationship between change in balance and self-reported handicap after
      vestibular rehabilitation therapy.
AB  - BACKGROUND AND PURPOSE: Dizziness and balance problems are two commonly reported
      symptoms of vestibular system disease, with subsequent alterations in lifestyle
      and reports of physical, functional and emotional handicap. Vestibular
      rehabilitation therapy (VRT) was developed to improve the functional status of
      patients with vestibular dysfunction. The aim of the present study was to
      investigate the relationship between change in balance performance and change in
      self-rated handicap after a four-week home exercise programme in 16 subjects with
      chronic vestibular disease. METHOD: Before and after the treatment intervention,
      balance was tested by use of a Smart Balance Master (SBM) system (Neurocom
      International, Clackamas, OR, USA) and self-rated handicap was measured by use of
      the Dizziness Handicap Inventory (DHI). RESULTS: Significant improvement was
      observed in both the SBM (p < 0.001) and DHI (p = 0.003) scores over the testing
      period. A moderately strong negative correlation existed between change in SBM
      and DHI scores (Spearman's r = -0.6). Further analysis using the DHI subscales
      indicated, however, that the emotional component showed no significant change
      over time, and a poor correlation with change in balance scores (Spearman's r = 
      0.39). CONCLUSIONS: These results indicate that a home-based exercise programme
      can significantly improve balance abilities in people with chronic vestibular
      dysfunction, but that outcomes may be enhanced by addressing the emotional issues
      associated with their disability.

PMID- 11833249
TI  - [Clinical utility of a commercial ligase chain-reaction kit for the diagnosis of
      pulmonary and extrapulmonary tuberculosis in the adult].
AB  - Microscopy with the Ziehl-Neelsen (ZN) stain is frequently negative in
      paucibacillary tuberculosis (TB) so that the treatment must be started and
      continued until the culture results confirm or not the disease. LCx Mycobacterium
      tuberculosis Assay (Abbott, Lab.) uses the ligase chain reaction for direct
      amplification of DNA and rapid detection of M. tuberculosis Complex (MTB) in
      clinical specimens. We evaluated the usefulness of the LCx assay on 1,203
      clinical samples: 737 respiratory and 466 extrapulmonary specimens. The LCx
      results were compared with those obtained by ZN and cultures on solid media and
      Mycobacteria Growth Indicator Tube (MGIT, Becton Dickinson, Argentina). Since
      detection and identification of MTB are simultaneously made by the LCx assay, a
      total of 145 out of 183 patients (79.2%) had a confirmed TB diagnosis in two
      working days. Positive culture results were predicted in 122 out of 160 cases
      (76.3%) by LCx and in 70 (43.8%) by ZN as well. The sensitivity (S) and
      specificity (ES) of LCx assay in ZN positive cases were 93.4% and 100.0% while in
      ZN negative cases they were 68.0% and 98.6%. The overall S and ES were 79.2% and
      98.7%, respectively. We conclude that the LCx assay is a rapid and sensitive
      technique, which can be a helpful diagnostic tool mainly for paucibacillary TB in
      reference laboratories.

PMID- 11833250
TI  - [The Mycobacteria Growth Indicator Tube (MGIT) is useful for anticipating the
      resistance of Mycobacterium tuberculosis to rifampicin but not to isoniazid].
AB  - A previously proposed MGIT protocol was assessed focussing on its reliability to
      test the mainstay antituberculous drugs. Isoniazid (H) (0.1 mg/l) and rifampin
      (R) (1 mg/l) were assayed against 109 Mycobacterium tuberculosis isolates
      affecting patients at high risk of multidrug-resistant tuberculosis. All isolates
      were simultaneously tested on Lowenstein-Jensen medium by the proportion method
      considered the gold standard. MGIT readings were accomplished within 2 and 22
      days after inoculation, at day 10, 93.4% of the tests were completed.
      Unsatisfactory to evaluate H activity, the assay misclassified 8.8% (5/57) H
      susceptible and 7.7% (4/52) H resistant isolates. Otherwise, it yielded correct
      results for all 60 R susceptible isolates and 93.9% (46/49) R resistant isolates.
      Properly backed-up by a conventional test and targeting high risk patients, the
      MGIT system proved to be a useful aid to anticipate most of resistance to R.
      Accuracy, cost and turnaround time were competitive compared with those of semi
      automated culture-based or molecular methods.

PMID- 11833251
TI  - [Production and characterization of monoclonal antibodies directed agains the
      major outer membrane protein and lipopolysaccharide of Chlamydia trachomatis].
AB  - Two monoclonal antibodies (MnAb) directed against the lipopolysaccharide (LPS)
      and major outer membrane protein (MOMP) of Chlamydia trachomatis were produced
      for use in indirect immunofluorescence (IFI). The specificity of the antibodies
      was determined by Dot-blot, Immunoblotting (IB) and IFI onto culture cells
      infected with C. trachomatis and IFI onto commercial swabs (MRL). The MnAb 2D3
      and 3C2 detected LPS and MOMP of C. trachomatis, respectively, by different
      methods. Neither MnAb showed cross-reactions when other gram-negative bacteria
      were used as antigens.

PMID- 11833252
TI  - [Comparative study of the Candida albicans genotypes isolated from
      immunocompromised patients and health carriers].
AB  - The aim of this study is to compare Candida albicans strain genotype isolates
      from oral cavity of immunocompromised patients due to different immunologic
      impairments with apparently normal carriers. Four populations were studied: 1)
      HIV positive hospitalized patients, 2) HIV negative immunocompromised patients
      (leukemia, lymphoma, organ transplant recipients), 3) drug addicts prior to AIDS
      pandemia in Argentina, 4) apparently normal carriers. DNA extracted was digested
      with the enzyme Eco RI, electrophoresed, transferred to nitrocellulose membrane
      and hybridized with the 27A probe labelled with 32P. The comparison between the
      profiles obtained permitted the differentiation of 16 genotypes. The distribution
      of the strains led to the conclusion that: a) all the isolated strains from AIDS
      patients were closely related and distributed in only three genotypes (1, 3, 11);
      b) a major genetic relationship between the isolates from AIDS patients and HIV
      negative immunocompromised patients was observed; c) strains from carriers showed
      a minor genetic similarity with those obtained from AIDS patients; d)
      characteristic profiles belonging to any of the studied groups were not found; e)
      significant genomic changes have not been observed during the last twenty years.

PMID- 11833253
TI  - [Vaginal candidiasis: etiology and sensitivity profile to antifungal agents in
      clinical use].
AB  - Candida vaginitis is one of the most frequent infection of the female genital
      tract with a high incidence. Approximately 75% of sexually active women suffer at
      least one episode of Candida vaginitis and 10% of them have recurrent episodes.
      Pregnancy, diabetes mellitus and antibiotic treatment are the most common
      predisposing factors, C. albicans is the etiologic agent most frequently found.
      The widespread reports of fluconazole resistance in Candida species and the
      selection of non Candida albicans prompted the study of species distribution of
      vulvovaginal candidiasis and their in vitro susceptibility against current
      antifungal agents. A total of 314 women with vaginal infection were studied.
      Yeasts were isolated from 104 patients with vulvovaginal candidiasis. The
      following species were identified: C. albicans 87.5%, C. glabrata 8.6% and 3.9%
      included C. krusei, C. famata, C. tropicalis and S. cerevisiae. The minimal
      inhibitory concentration (MIC) was determined for nystatin, isoconazole,
      fluconazole and ketoconazole, using a broth microdilution method based on NCCLS
      procedure. Although most of the isolates were C. albicans, the high percentage of
      C. glabrata recovered suggests the need to identify the yeasts isolated.
      Fluconazole resistant C. albicans were isolated in 13.46% of the cases. Thus,
      further studies are required to correlate the possible role of these strains in
      recurrent vulvovaginal candidiasis.

PMID- 11833254
TI  - [Degradation of anthraquinone blue by Trametes trogii].
AB  - The ability of the white rot fungus Trametes trogii BAFC 463 (high producer of
      ligninolytic enzymes, especially laccase and manganese peroxidase) to degrade the
      dye anthraquinone blue, refractory to bacterial attack, was evaluated. Both
      tropho- and idiophasic T. trogii cultures in synthetic medium
      (glucose/asparagine) and complex medium (malt extract/glucose) were able to
      transform up to 88% dye in 4 hours. The activity of laccase, an oxygen-dependent
      phenoloxidase which was present at high levels in all the conditions assayed,
      might be related to the ability of the fungus to degrade the colorant. This is
      supported by the fact that in bioreactor experiences carried out at pH 4.5 the
      addition of anthraquinone blue caused a decrease in the levels of soluble oxygen.
      However, although high levels of laccase were produced at pH 7.5, the enzyme was
      not active, and neither dye transformation nor loss in the levels of soluble
      oxygen were quantified.

PMID- 11833255
TI  - [Resurgence of measles in the province of Cordoba, Argentina, in 2000].
AB  - Since 1993, ministers of health of countries of America established as a goal the
      eradication of measles by the year 2000. As a consequence of measles eradication
      vaccination strategy there has been a reduction in the incidence of reported
      cases. Despite that, measles has continued occurring in epidemic outbreaks in
      many Argentinian provinces. This paper describes and analyzes the outbreak which
      occurred at Cordoba province, in 2000. Out of 46 serum samples analyzed from
      suspected cases, 6 (13.3%) were confirmed as measles by indirect
      immunofluorescence and enzyme immunoassays. All of them were detected in Cordoba
      city among both without vaccination data and unvaccinated individuals. The
      epidemiological links among the measles cases could be established although the
      geographic source of measles importation as well as the primary infection source
      remain unknown. The highest measles incidence was observed in the group > or = 20
      year old (50%), followed by the pre-school age group (< or = 4 year old, 33.3%).
      The active vaccination data directed against the suspected case contacts along
      with a high measles population immunity probably contributed to restrict the 2000
      outbreak.

PMID- 11833256
TI  - [Neutralization test for lymphocytic choriomeningitis virus for distinguishing
      between two arenavirus infections in Argentina].
AB  - The active coexistence of two pathogenic arenaviruses, Junin (JUNV) and
      lymphocytic choriomeningitis (LCMV), in the same region of Argentina, has been
      known since the early 70's, and records of clinical and subclinical human
      infections by one and/or the other agent have been continuously produced for the
      last 25 years. Anti-LCMV antibody is currently searched only by indirect
      immunofluorescence, a test that shows cross reactions among a number of
      arenaviruses yielding, in the cases of LCMV and JUNV consecutive infections, a
      concomitant seroconversion for both viruses, as an inconclusive diagnostic
      result. In contrast, neutralization (NT) tests reveal arenavirus antibodies
      directed to unique epitopes on these virus envelopes, thus allowing to disclose
      the sequence in the cases of consecutive infections. In this paper, the
      characteristics of neutralization (NT) test for LCMV in cell cultures are
      described, as well as its performance in the field diagnosis of LCMV human
      infections. The native LCMV strain Cba An 13065 was inoculated on L-929 cell
      (ATCC CCL 1), and procedures were followed to perform a constant virus-variable
      serum NT test. Final points of sera titrations were expressed as the maximal
      serum dilution that yielded 75% of pfu inhibition. This NT test was assayed on
      paired serum samples of 36 patients with confirmed Argentine hemorrhagic fever
      (AHF) (a disease caused by JUNV), who had had a known previous contact with LCMV
      through IFI. The use of this one test led to confusing diagnosis of the disease
      due to concomitant seroconversion for JUNV and LCMV. By using NT test, it was
      shown that: some of them were possibly not infected by LCMV, and that 30/36 cases
      (83.3%) had a pre-existing level of LCMV antibody, with titers in the range of 5
      to 640, remaining unchanged 60 days after the clinical AHF. This shows that NT
      antibodies to LCMV are not influenced by the outcome of the immune response to
      JUNV, thus confirming the efficiency of NT test as identificator among
      arenaviruses. To assess the performance of this NT test in individuals having
      only IFI antibodies to LCMV, 126 serum samples obtained through serological
      surveillance in a rural area of Argentina, were used. It was found that NT had
      improved coincidence with IFI as IFI titers increased. Interpretations were based
      on the pan-arenavirus antibody response obtained by using IFI as the only test.
      Results presented herein prove that the described NT test is a valuable tool for
      the detection of LCMV infections, particularly when a previous infection with
      LCMV has to be demonstrated during the acute phase of Argentine hemorrhagic
      fever.

PMID- 11833257
TI  - [Effect of chlorhexidine on Staphylococcus aureus hospital isolates under
      different environmental conditions].
AB  - Antiseptic agents are widely used in hospitals, being essential when prevention
      and control of nosocomial infections are required. It is necessary to consider
      several aspects that affect the biocide activity, since they have direct
      incidence in hospital hygiene, health and also in the nosocomial infection rate.
      Organisms belonging to Staphylococcus genus are involved in such infections and,
      digluconate of chlorhexidine is one of the most used antiseptic agents for human
      and animal health. The current study involved the evaluation of this biocide
      agent against 19 nosocomial isolates of Staphylococcus with and without organic
      substances and applying distilled water and water of 300 ppm hardness as dilution
      means. Results show that hard water was one of the factors that most highly
      affected the bactericidal activity of chlorhexidine. Moreover we found that it
      affected bactericidal activity more than the interference generated by organic
      substances. Our study proves that chlorhexidine is an effective antiseptic for
      these gram-positive microorganisms.

PMID- 11833258
TI  - [Evidence-based health promotion].

PMID- 11833259
TI  - [Review of published works on Spanish youth health promotion].
AB  - The objective of this study is to review the health promotion interventions on
      spanish youths published in Spanish in the 1995-2000 period and to describe them
      in accordance with the scope within which they have been carried out, the topics
      addressed, the methodology, the evaluation design used and the results obtained.
      Two hundred and fourteen intervention were identified. Illegal drugs were the
      topic on which the largest number of interventions were focused (29.8%), followed
      by alcohol (15.9%), the risk-related sexual behaviours (14.6%) and leisure time
      (12.6%). The activities carried out most often were: participation-based
      educational methods (30.7%), explanatory education methods (11.5%) and the
      preparation of educational materials (11%). In 80.8% of the cases, some
      evaluation of the health promotion activities was found. The type of evaluation
      employed most often was the process evaluation (73.7%), and the medium-long term
      results evaluation being those employed the least (2.2%). The evaluation
      methodologies used most often were questionnaires (28.2%). A combination of
      qualitative and quantitative methods was employed in 13.2% of the cases. The four
      interventions in which the medium-long term impact was gauged had the purpose of
      preventing and reducing cigarette smoking and/or drinking and or marijuana
      smoking, all of these initiatives achieving a reduction in cigarette smoking. In
      conclusion, it seems necessary to improve the design of the evaluations of the
      health promotion initiatives addressed to young people in Spain and to increase
      the dissemination of the same by way of their publication.

PMID- 11833260
TI  - [The transversality and health promotion schools].
AB  - The following article shows the evolution of the schools contribution to the
      Health Education of children and young people. Moving on from the traditional
      concept of health, today, Health Education has a general and global meaning,
      which encompasses all of the physical, psychological and social aspects of
      health. These aspects define the characteristics of the "Healthy School". The
      need to broach the "transversal subject" offers schools the possibility of
      developing "transversality" in the Health Education. Finally, the concept of
      promoting health defines, together with the other subjects, that which we
      understand by "the heath promotion schools", which attempts to progress the full
      integration of schools in the society in which they are located.

PMID- 11833261
TI  - [Influence of social inequality, social unrest and extreme poverty on
      tuberculosis morbidity in the City of Barcelona].
AB  - BACKGROUND: The main purpose of this study was to analyse inequalities between
      tuberculosis/intravenous drug user and tuberculosis/not intravenous drug user
      among the different neighbourhoods of Barcelona and the relationship to
      socioeconomic indicators and social/material deprivation indicators throughout
      the 1990-1995 period. METHODS: An ecological study which included all cases of
      tuberculosis among residents of Barcelona, the analysis unit being the
      neighbourhood. Intravenous drug users within the 15-49 age range and non
      intravenous drug users over age 14 were included. The mean annual incidence rate
      standardized by age was used. The social indicators considered were the inner
      city areas, unemployment, less than primary education, overcrowding, social
      unrest and extreme poverty. In the bivariate analysis, the relationship between
      tuberculosis incidence and the social indicators was studied by means of the
      Spearman correlation coefficient, and the multivariate analysis by means of the
      Poisson regression. RESULTS: The incidence rates were higher in the inner city
      neighbourhoods, followed by the newer outlying working class neighbourhoods in
      both groups studied, and in other older outlying districts for the non-users of
      intravenous drugs. Among the intravenous drug user group, the variables related
      to a greater risk of tuberculosis were: man (RR = 7.42, confidence interval at
      95% ICI95%-: 6.16-8.93), age (RR = 61.51, CI95%: 34.64-109.20), unemployment (RR
      = 1.68, CI95%: 1.51-1.88), social unrest (RR = 1.29, CI 95%: 1.04-1.58),
      overcrowding (RR = 1.36, CI 95%: 1.19-1.55) and inner city areas (RR = 1.92, CI
      95% 1.48-2.50). Among the male non-users of intravenous drugs, no interaction
      between unemployment and age was found. Neighbourhoods with extreme poverty and
      inner city neighbourhoods showed a higher risk of tuberculosis (RR = 1.11, CI 95%
      1.08-1.135 and RR = 1.80, CI95%: 1.51-2.14). Among the female non-users of
      intravenous drugs, a relationship was found in those of lesser age (RR = 1.29, CI
      95%: 1.05-1.57), unemployment (RR = 1.18, CI 95%: 1.09-1.26), extreme poverty (RR
      = 1.95, CI 95%: 1.56-2.45) and inner city areas (RR = 1.72, CI 95%: 1.35-2.19).
      CONCLUSION: Inequalities in tuberculosis are related to different social
      indicators such as unemployment and inner city areas. A difference exists between
      the two groups studied. Tuberculosis is related with social unrest and
      overcrowding among intravenous drug users and with extreme poverty among non
      users of intravenous drugs.

PMID- 11833263
TI  - [Oral health of school children in Ceuta. Influences of age, sex, ethnic
      background and socioeconomic level].
AB  - BACKGROUND: The objective of this study is that of gauging the prevalence of
      dental caries, periodontal disease and malocclusion among the school-age
      population of Ceuta and the spread thereof by age, sex, ethnic background and
      father's occupation. METHODS: Prevalence survey of a multistage, stratified,
      random sample of schoolchildren 7, 12 and 14 years of age (n = 347) in order to
      calculate DMFT and dmft indexes--permanent and deciduous dentition--, CPITN and
      malocclusion. Assessment of the statistical significance of the differences
      encountered according to age, sex, ethnic background and socioeconomic status
      using the Chi-Square, Student T and Snedecor F tests. To calculate, among
      schoolchildren ages 12 and 14, the odds ratios of showing a DMFT index over 4 and
      their 95% confidence intervals by gender, ethnic background and the socioeconomic
      status. RESULTS: Dmft (decayed, filled and missing teeth) was 3.02 at 7 and DMFT
      was 3.91 at 12 and 4.46 at 14. Odds ratios of DMFT > 4 were 2.26 by gender (95%
      CI = 1.27-4.05), 2.17 by ethnic group (95% CI = 1.18-3.99) and 1.8 by SES (95% CI
      = 0.85-3.81). In schoolchildren of low SES--unemployed father's--OR by ethnic
      group was 1.37 (95% CI = 0.28-7.0). No statistically significant differences were
      found in the distribution of malocclusion and periodontal disease--except by age.
      CONCLUSIONS: Dmft and DMFT values are in Ceuta higher than the mean national
      values and the proposed value of the WHO for the year 2000. Risk of DMFT higher
      than the median is 2.3 in girls compared with boys, 2.17 in Moslem compared with
      non Moslem and 1.8 in low SES schoolchildren--unemployed father's--compared to
      other SES schoolchildren. The increased risk related to ethnic background is
      influenced by SES.

PMID- 11833262
TI  - [Factors related to the health education practice for primary care physicians in
      Galicia, Spain].
AB  - BACKGROUND: Health education on the part of primary care physicians has been
      shown to improve the health of the population, but, generally speaking,
      physicians are not pursuing this to the recommended degree. The end purpose of
      this study is that of ascertaining what factors have an influence on health
      education being carried out by primary care physicians in Galicia (Spain), how
      they perceive their training in this regard, what obstacles they encounter as
      regards to providing this education and how the existence of unhealthy habits on
      the part of the physician has a bearing on carrying out this activity. METHODS: A
      cross-sectional study has been conducted. A previously-tested, self-answer mail
      out questionnaire was sent to a random sample stratified by provinces of 420
      primary care physicians from the "Servicio Galego de Saude" (Galician Health Care
      Service). A comparative analysis was made with those who failed to reply. The
      main analysis of the data was conducted by means of a multivariate (logic
      regression) analysis. RESULTS: Seventy-three percent (73%) of the replies were
      valid, without any differences among strata. Sixty-four percent (64%) of the
      physicians surveyed considered their training in health education to be
      insufficient, being better among family doctors and among those who had taken
      courses specifically devoted to this subject. The main obstacle reported was the
      lack of time. 38.4% of the physicians reported that they carry out health
      education, an activity related to the female gender (Odds Ratio 1.70), better
      training concerning this subject (Odds Ratio 2.20) and a better personally
      perceived ability to carry out the same (Odds Ratio 1.32). No relationship was
      found to exist between the carrying out of health education and the existence of
      unhealthy habits. CONCLUSIONS: Being female, feeling efficient at providing
      health education and considering oneself to be well-trained regarding this
      subject being related positively to this activity being carried out by primary
      care physicians, solely one third of whom report doing so.

PMID- 11833264
TI  - [Prevalence of tuberculosis among the immigrant population in Ceuta, Spain].
AB  - BACKGROUND: The immigrant populations from sub-Saharan and Maghreb countries are
      groups in high risk of contracting tuberculosis. An analysis is made of the
      prevalence of tuberculosis infection among one group of these immigrants in Ceuta
      for the purpose of finding possible differences in their incidental behavior
      according to the country or geographical region from which they came. METHODS: A
      descriptive cross-sectional study of a sample of 2,223 immigrants (1979 males and
      244 females) from different African countries (mainly Nigeria, Mali, Guinea
      Bissau, Cameroon, Ghana, Sierra Leona, Democratic Republic of Congo and Liberia)
      at the Calamocarro refugee camp in Ceuta. A Mantoux intradermic reaction test was
      performed following the previously-established protocol, the data for three cut
      off points being presented. RESULTS: The immigrants came from 36 African
      countries, 89.0% being males and 11.0% females (p < 0.001), respectively
      averaging in age from 24.9 +/- 4.3 to 23.4 +/- 4.1. A reaction to the Mantoux
      text of 10 mm or more was found in 32.6%, that is 33.2% among males and 27.9%
      among females (p = 0.09). Solely 1.1% showing 5-10 mm hardening of probable
      vaccination-related cause. By geographical regions, the highest rates were found
      among immigrants from the Democratic Republic of Congo (65.1%) and Cameroon
      (48.4%), followed far behind by Nigeria (34.0%), Liberia (32.7%), Mauritania
      (29.1%), Sierra Leona (28.8%), Ivory Coast (27.8%), Guinea-Bissau (27.4%), Ghana
      (26.3%), Algeria (25.6%), Mali (24.1%) and the Republic of Guinea (20.9%) (p <
      0.0001). CONCLUSIONS: The immigrant population from central African countries
      shows a higher prevalence of tuberculosis infection, comprising a group at risk
      of contracting this disease. Therefore, it is of fundamental importance to
      implement specific programs to actively detect tuberculosis infection during
      their stay in our city, taking advantage of their being grouped together upon
      entry into our country, prior to their final emigration to localities throughout
      the mainland and subsequent mixing among the host country population.

PMID- 11833265
TI  - [The effect on the use of hospital resources in a geriatric domiciliary care
      program among the elderly patients with advanced cardiorespiratory diseases].
AB  - BACKGROUND: One of the objectives of the geriatric home care teams is that of the
      follow-up of elderly patients having a high risk of hospital readmission.
      Although they have been operating in our country for years, no data shows the
      impact on the use of hospital resources in accordance with this follow-up. The
      objective of this study is that of analyzing the effect which the monitoring, by
      geriatric home care unit, involves on patients having very advanced chronic
      cardiorespiratory disease. METHODS: The patients with chronic cardiorespiratory
      disease followed up by the unit during the January 1995-January 1999 period were
      included, excluding those on follow-up for less than 3 months. A comparison is
      drawn among the number of hospital emergency room visits, hospital admissions and
      days of hospitalization for the year prior to the care provided by the unit and
      throughout the follow-up time thereof are compared. RESULTS: Eighty-one (81)
      patients, mean age 80.57 years (DE 7.39) and a median length of care per unit of
      nine (9) months (5-13.5), were included in the study. The uses per patient and
      month of follow-up decreased by 0.07 Emergency Room visits (0.02-0.11) (p =
      0.04), 0.10 hospital admissions (0.07-0.14) (p < 0.001) and 2.01 days of
      hospitalization (1.87-2.15) (p < 0.001). CONCLUSIONS: A specialized geriatric
      home care unit reduces the use of hospital resources on elderly people diagnosed
      as severe chronic cardiorespiratory disease.

PMID- 11833266
TI  - [Initial experience with surgical decompression of the vein in branch retinal
      vein occlusion].
AB  - Due to the development of the armamentarium and surgical techniques, the
      indications of pars plana vitrectomy (PPV) are expanding. It concerns also a
      relatively new indication, as is the branch retinal vein occlusion (BRVO) of the
      temporal part of the posterior pole of the retina with the secondary involvement
      of the macular region. The purpose of this prospective study is to demonstrate
      anatomical and functional results after the surgical decompression of the
      occlusion of the branch retinal vein draining the macular region. Since November
      1999, 3 patients, one woman and 2 men (age 70, 47 and 76 years) with the quadrant
      BRVO of the temporal part of the retina involving the macular region were
      followed. The visual acuity before the surgery in all 3 patients was 6/36 (20/120
      or 0.16) and the BRVO lasted for 3-5 months. The patients were examined by
      slitlamp biomicroscopy, and the course of the disease was documented by means of
      red-free fundus photographs as well as fluorescein angiograms. In all three
      patients, PPV and the adventitial sheathotomy of the arteriovenous crossing (AVC)
      were performed. Surgical decompression of BRVO and reperfusion of the ischemic
      part of the retina was achieved by separating the overlying arteriole from the
      venule at AVC. Neither per- nor postoperative complications were noted. In two
      patients, the visual acuity improved to 6/12 (20/40 or 0.5), and in the last one
      stabilized at 1/9 (20/180 or 0.11). The minimal follow-up period was 12 months.
      In conclusion, we recommend to performing this new type of delicate surgery
      procedure in individual cases on the basis of detailed biomicroscopial
      examination and fluorecein angiograms by an experienced vitreoretinal surgeon.

PMID- 11833267
TI  - [Tears of the retinal pigment epithelium] ].
AB  - The authors describe spontaneous tears of the retinal pigmented epithelium in
      three eyes of two patients with age-related macular degeneration. In all
      instances the development of the tear was associated with an occult choroidal
      neovascular membrane detected by fluoroangiography. The authors describe typical
      clinical features and contemporary views regarding the pathogenesis of the tear.

PMID- 11833268
TI  - [Peroperative use of mitomycin C in excision of primary pterygia].
AB  - The authors in a retrospective study assess the recurrence rate of pterygium
      after the application of a single intraoperative dosage of topical Mitomycin C
      during the pterygium excision. The group involves 21 eyes of 19 patients with
      primary pterygia. When using technique of simple pterygium excision followed by
      application 0.02% MMC onto a bare sclera in duration 3 minutes, pterygium
      recurred in 5 patients (23.8%). The authors noticed a distinct difference in
      pterygium recurrence relating to the age of patients. Under the age 50 the
      recurrence occurred in each of 4 patients, above the age 50 only in one out of 17
      patients (5.9%).

PMID- 11833269
TI  - [Capsulectomy via the pars plana--one of the possible definitive treatments for
      opacification of the posterior capsule] ].
AB  - The author demonstrates on a group of 27 eyes a possible definite solution of a
      serious complication of successful operation of cataract, i.e. secondary
      cataract. The latter reduces due to its frequent incidence markedly the visual
      acuity. The approach with a vitrectome via the pars plana is a simple and
      permanent solution which beyond doubt has advantages as compared with YAG
      capsulotomy and polishing of the posterior capsule. The method is effective,
      cheap and the incidence of complications is minimal. Fluoroangiographic findings
      confirm its safety.

PMID- 11833270
TI  - [Penetrating intraocular injuries caused by foreign bodies of organic origin] ].
AB  - OBJECTIVE: To demonstrate two eyes of two patients with a penetrating injury by
      an organic intraocular foreign body (CNT), to outline the course of treatment and
      to evaluate anatomical and functional results. MATERIAL AND METHODS: During the
      period between May and July 1999 the authors treated at their department an 11
      year-old girl and a 17-year old boy with a penetrating CNT injury of organic
      origin. In the girl they extracted a CNT which pierced the sclera and protruded
      into the vitreous body. The foreign body was extracted by means of a forceps, the
      site of perforation was treated by a cryosurgical procedure with a radial
      Silastic filling. The man was shot into the OL by a grain of pepper from an air
      gun. The organic body in the vitreous body caused a violent inflammatory reaction
      in the vitreous body and retina. Early extraction of the CNT could not be made
      because of an adverse corneal finding which made surgery impossible. The
      progressing proliferative vitreoretinopathy (PVR) led to repeated formation of
      epiretinal, subretinal and cyclitic membranes which caused relapsing detachment
      of the retina (OS). The foreign body was extracted during pars plana vitrectomy
      (PPV) by the transvitreal route using a forceps. Definite adherence of the retina
      was achieved during the third PPV, membranectomy and implantation of silicone oil
      (SO). Final functional success was achieved by eliminating SO and by partial
      perforating keratoplasty. RESULTS: The CNT in the girl was histologically and
      parasitologically identified as a fibre of animal origin (animal hair or human
      eyelash). The follow up period is six months, VOP-5/5 nat., NOT 17 torr, bulbus
      undisturbed. In the second patient the cultivation finding from the vitreous body
      was negative. Extensive PVR developed as a result of breakdown products of the
      organic CNT and led to relapsing OS. Three months after the last operation the
      bulbus is at rest, the corneal disc clear, the retina attached, VOL-3/60 s + 8.0
      D steop., NOT 12 torr. CONCLUSIONS: The final results of treatment of severe
      devastating penetrating injuries by a CNT is determined by the preoperative
      condition of the ocular tissues. CNT of organic origin damage intraocular tissues
      by their breakdown products as well as by more frequent contamination with
      pathological microorganisms. Our experience provided evidence that penetrating
      injuries by non-infected CNT of organic origin have a favourable prognosis. But
      even relapsing and prolonged OS after extraction of the CNT of organic origin and
      endophthalmitis need not lead to loss of the eye or its function.

PMID- 11833271
TI  - [Pars plana vitrectomy in retinopathy of prematurity].
AB  - Retinopathy of prematurity (ROP) is a proliferative retinopathy which affects pre
      term infants. ROP occurs primarily at the advancing edge of vascularization and
      consists of arrested spread of vessels, proliferation of endothelial cells,
      formation of arteriovenous shunt and in some cases, neovascularization. To date
      only the surgical approach for advanced ROP is acceptable, other ways are still
      in experimental stages of development. PURPOSE: Because of the early development
      of fibrovascular proliferative tissue, vitreous surgery before the fovea is
      pulled anteriorly, may lead to successful results. METHODS: Data from literature
      and own experiences lead the authors to use retinal re-attachment procedures to
      restore normal anatomic relation between the retina and choroid in affected eyes.
      RESULTS: 6 cases demonstrated that retinal detachments caused by fibrous
      proliferations that pull the retina upward to a fibrotic membrane on the
      posterior lens capsule can be treated successfully. CONCLUSION: Stages ROP when
      the retinal detachment threatening fovea are recommended for successful surgical
      repair of retinal detachment in ROP only.

PMID- 11833272
TI  - [PRK and LASIK in patients with myopia ranging from -6 to -9 D] ].
AB  - OBJECTIVE: Observing of effectiveness, safety and short-term stability of
      patients with myopia ranging from -6.0 to -9.0 diopters (D) after surgery and
      their comparison. PARTICIPANTS AND METHOD: We were retrospectively analyzing pre-
      and postoperative outcomes of patients with myopia ranging from -6.0 to -9.0 D.
      90 eyes were examined before laser in situ keratomileusis (LASIK) with mean
      spherical equivalent refraction -7.64 +/- 0.84 D and mean cylinder -1.23 +/- 1.1
      D. 56 eyes were examined before photorefractive keratectomy (PRK) with mean
      spherical equivalent refraction -6.92 +/- 0.72 D and mean cylinder -0.60 +/- 0.55
      D. Patients were examined before operation, one week, one month, three months,
      six months, nine months and one year after operation. Data were collected and
      analyzed by the computer programme. RESULTS: We observed the patients who
      underwent the operation and six months after surgery we received following
      results: After PRK mean spherical equivalent refraction was -0.23 +/- 1.24 D,
      mean cylinder -0.83 +/- 0.42 D, uncorrected visual acuity (UCVA) 0.86 +/- 0.35,
      best spectacle-corrected visual acuity (BCVA) 1.13 +/- 0.33. After LASIK mean
      spherical equivalent refraction was -0.29 +/- 1.19 D, mean cylinder -1.14 +/-
      0.77 D, UCVA 0.65 +/- 0.25, BCVA 0.83 +/- 0.25. One year after PRK mean spherical
      equivalent refraction was -0.44 +/- 1.26 D, mean cylinder -0.80 +/- 0.57 D, UCVA
      0.81 +/- 0.31, BCVA 0.97 +/- 0.21. After LASIK mean spherical equivalent
      refraction was -0.14 +/- 0.86 D, mean cylinder -1.26 +/- 0.89 D, UCVA 0.75 +/-
      0.25, BCVA 0.89 +/- 0.20. CONCLUSIONS: Both methods are effective and their
      results after 3 to 6 months after laser treatment in patients with myopia ranging
      from -6.0 to -9.0 D were comparable. Based on the complex evaluation, we prefer
      LASIK nowadays.

PMID- 11833274
TI  - [Monitoring intraocular pressure and therapy after trabeculectomy in both eyes
      during a 2-year period].
AB  - PURPOSE: To evaluate the level of intraocular pressure (IOP) and glaucoma therapy
      during two years after trabeculectomy (TE) with two releasable sutures (RS) on
      the first and the second operated eye. METHODS: In a retrospective study,
      preoperative and postoperative IOP and glaucoma therapy in 40 patients with open
      angle glaucoma, were evaluated. Patients underwent standardized TE with two RS on
      both eyes performed by the same surgeon. The first (worse) eye was operated on an
      average of three years after the diagnosis of glaucoma, and after 8.2 +/- 6.9
      months the second (better) eye was operated on. RESULTS: TE with RS significantly
      decreased the level of IOP (p < 0.0001) and therapy (p < 0.0001) during a two
      year follow up period. There was no significant difference in IOP (p = 0.226) and
      glaucoma therapy (p = 0.086) between the first and the second operated eye. IOP
      was stabilised within 2-3 months after surgery for most patients, however
      glaucoma therapy was added for some to keep the target pressure. After one year
      IOP and therapy were stable for all patients. CONCLUSION: There is no difference
      between the first-worse and the second-better operated eye regarding IOP and
      glaucoma therapy during a two year period.

PMID- 11833273
TI  - [Immediate and late intraocular pressure levels after trabeculectomy with
      releasable sutures] ].
AB  - PURPOSE: To evaluate the level of IOP and clinical status the first day after
      trabeculectomy (TE) with releasable sutures (RS), to follow up the extraction of
      RS in correlation with early and late postoperative level of IOP. METHODS: In a
      retrospective study, 40 patients with open angle glaucoma were followed. They
      underwent TE with two RS on both eyes. RESULTS: Hypotony (IOP less than 6 mmHg)
      was noted in 15 eyes (19%) the first day after the operation, shallow anterior
      chamber in 5 (6%). An IOP level higher than 20 mmHg was found in 11 eyes (13%)
      one day after surgery. No RS were extracted in the first group of 26 eyes. The
      early mean IOP was 10.15 +/- 7.1 mmHg the 1st day after surgery. IOP increased to
      a mean level of 15.3 +/- 3.8 mmHg two years after TE, 65% of eyes were without
      glaucoma therapy. One RS was extracted in the second group of 28 eyes. The early
      mean level of IOP was 10.7 +/- 6.5 mmHg, the late level 13.9 +/- 3.7 mmHg. The
      target pressure was maintained in 68% of the eyes without additional glaucoma
      therapy. The third group had 26 eyes and two RS were extracted after TE. The
      early mean level of IOP was 14.7 +/- 6.9 mmHg, the mean level of IOP was 15.8 +/-
      3.9 mmHg two years after surgery, 39% of eyes were without glaucoma therapy.
      CONCLUSION: A level of IOP the first day after the operation, lower than 6 mmHg
      or higher than 20 mmHg, must not be an indicator for failure of the surgery.
      Observing the level of IOP 3-5 days after surgery determines whether the RS is to
      be removed or not. The use of RS prevents short-term complications and the
      extraction of RS during the postoperative period can positively influence the
      evaluation of filtration.

PMID- 11833275
TI  - [Use of the perichondrium failed trabeculectomy].

PMID- 11833276
TI  - [Dr. med. vet. h. c. Peter Knusel (1857-1944): veterinarian, cattle-breeder and
      politician in Lucerne].

PMID- 11833277
TI  - From the Marshall plan to present day prosperity: veterinary medicine in The
      Netherlands 1945-2000.

PMID- 11833278
TI  - [Development of animal protection in the canton of Vaud].

PMID- 11833279
TI  - [The Swiss Military Veterinary Service since 1960].

PMID- 11833280
TI  - Comparative karyology of Brazilian vampire bats Desmodus rotundus and Diphylla
      ecaudata (Phyllostomidae, Chiroptera): banding patterns, base-specific
      fluorochromes and FISH of ribosomal genes.
AB  - This paper provides new data on chromosomes of Brazilian vampire bats Desmodus
      rotundus and Diphylla ecaudata. These species were analyzed by GTG, CBG- and CB
      DAPI banding, AgNO3/CMA3 sequential staining, base-specific fluorochrome dyes and
      in situ hybridization with 18S rDNA probe. C-banding (CBG) revealed constitutive
      heterochromatin in the pericentromeric regions in all autosomes and the X and Y
      chromosomes appeared entirely heterochromatic in both species. CB-DAPI revealed a
      coincident banding pattern to that obtained by CBG. Triple staining CMA3/DA/DAPI
      revealed an R-banding and a weak G-banding pattern in the karyotypes. Sequential
      AgNO3/CMA3 staining showed a NOR located interstitially on the long arm of pair 8
      in D. rotundus and on the short arm of pair 13 in D. ecaudata. FISH with a rDNA
      probe confirmed the location and number of NORs; a difference neither in
      intensity nor in size of hybridization signal was detected between homologues for
      both species.

PMID- 11833281
TI  - Phylogeographic relationships of Ixodes uriae (Acari: Ixodidae) and their
      significance to transequatorial dispersal of Borrelia garinii.
AB  - The seabird tick Ixodes uriae (Acari: Ixodidae) has a bi- and circumpolar
      distribution and is commonly infected with Lyme disease Borrelia. Identical
      Borrelia flagellin gene sequences have been detected in I. uriae from both the
      Northern and Southern Hemispheres, suggesting a transequatorial transport of
      Borrelia. Parsimony analysis of the internal transcribed spacer 2 (ITS2) and a
      part of 16S rDNA of I. uriae from the Northern and Southern Hemispheres indicated
      that northern and southern I. uriae might be reproductively separated. We
      hypothesize that Borrelia is probably not dispersed from one hemisphere to the
      other by ticks attached to seabirds.

PMID- 11833282
TI  - Trends in the karyotype evolution of Loricariidae fish (Siluriformes).
AB  - Six species of Loricariidae belonging to the subfamilies Hypostominae (Hypostomus
      emarginatus, Rhinelepsis aspera, Pogonopoma wertheimeri), Ancistrinae (Panaque
      cf. nigrolineatus, Hemiancistrus sp.) and Loricariinae (Sturisoma cf.
      nigrirostrum) were studied cytogenetically. The results show that 2n = 54
      represents the basal diploid number for this fish family. Different trends in the
      karyotypic evolution can be seen among the subfamilies: Hypostominae and
      Loricariinae species present diversified karyotypic macrostructures, while the
      Ancistrinae appear to show more conserved karyotypes. Among the Hypostominae, the
      genus Hypostomus had a wide karyotypic variation (2n = 52 to 80), where centric
      fissions seem to play an important role in this chromosomal divergence. The
      nucleolar organizing regions were diversified, and occurrence of multiple NORs
      was frequent. Heteromorphic chromosomes belonging to distinct sex chromosome
      systems can also occur infrequently among the Loricariidae.

PMID- 11833283
TI  - Genetic basis of variation of yield, and yield components in mungbean (Vigna
      radiata (L.) Wilczek).
AB  - Additive, dominance, and epistasis genetic basis of seed yield per plant, number
      of pods per plant, number of seeds per pod, and 1000 seed weight in mungbean
      (Vigna radiata (L.) Wilczek) have been examined, using Triple Test Cross (TTC)
      analysis. The material for TTC test was evaluated in two seasons i.e., kharif
      (July-October) and spring/summer (March-June), at the research station of the
      Nuclear Institute for Agriculture and Biology (NIAB), Faisalabad, Pakistan.
      Epistasis was present significantly for number of pods per plant and number of
      seeds per pod when grown in the spring/summer season (March to June). Partition
      of epistasis showed that additive x additive ('i' type) interaction was an
      important component of number of pods per plant, and number of seeds per pod was
      found to be of both types 'i' type, and additive x dominance, and dominance x
      dominance ('j' and 'l' type) interactions. This indicated that epistasis might be
      a non-trivial factor in the inheritance of pods per plant, and seeds per pod in
      mungbean. The expression of epistasis was influenced differentially by particular
      genotypes, indicating that a limited number of genotypes may not be sufficient to
      detect non-allelic interactions for a trait in mungbean. Additive and dominance
      genetic components were significant for all four traits in kharif season (July to
      October) but only for seed yield and 1000 seed weight in spring/summer season.
      This suggests that the genes controlling seed yield per plant, and 1000 seed
      weight are equally sensitive to the environment. The predominance additive gene
      action in those traits is not significantly influenced by epistasis, suggesting
      that improvement of the traits can be achieved through standard selection
      procedures.

PMID- 11833284
TI  - Unravelling the phylogeny of tetraploid Vicia amoena (Fabaceae) and its diploid
      relatives using chromosomal landmarks.
AB  - The chromosomal sites of 5S and 45S rDNA genes were revealed by fluorescence in
      situ hybridisation, and used as landmarks to resolve the ambiguous taxonomic
      status of the tetraploid Vicia amoena var. amoena (Fabaceae). Comparisons of the
      number and location of rDNA loci in V. amoena var. sericea, V. pseudorobus, V.
      dumetorum, V. pisiformis and V. cracca confirmed that V. amoena var sericea, or a
      closely related diploid, was a likely progenitor of the tetraploid. However, the
      tetraploid contains chromosomes bearing rDNA loci which are probably derived from
      another species, such as V. pseudorobus, suggesting that it is an allotetraploid
      and the product of an interspecific hybridisation event. This was corroborated by
      fluorescence in situ hybridisation with genomic DNA from V. amoena var sericea,
      which not only showed that the tetraploid contains more than one chromosome set,
      but also that its constituent sets have undergone considerable reorganisation.

PMID- 11833285
TI  - Cytotaxonomic considerations on Neotropical Psittacidae birds and description of
      three new karyotypes.
AB  - Chromosomes obtained from feather tissues of 14 species of Brazilian Psittacidae
      were analyzed by Giemsa conventional staining and the karyotypes of Ara
      chloroptera, Propyrrhura maracana and Nandayus nenday are presented for the first
      time. The remaining species showed no chromosome differences when compared with
      previous literature data. Two basic karyotype patterns were observed. A karyotype
      pattern is mostly characterized by biarmed macrochromosomes, while in the other
      one most macrochromosomes are telocentrics.

PMID- 11833286
TI  - Phylogenetic relationships among Portuguese rye based on isozyme, RAPD and ISSR
      markers.
AB  - The phylogenetic relationships of 10 rye landraces and cultivars from the north
      of Portugal and from Brazil were analysed using 20 isozyme loci, and a total of
      511 PCR markers (342 ISSRs and 169 RAPDs). The isozymes were analysed in at least
      100 plants of each population/cultivar and, therefore, we have data about intra
      and inter population/cultivar genetic variability. However, the analyses with
      ISSRs and RAPDs were obtained using a mix of 25 plants of each population.
      Therefore, each population/cultivar was reduced to one tube and we have no data
      about intra genetic variability. As expected in a cross pollinated crop we found
      genetic diversity and a larger variation within than among the populations using
      isozymes. Somewhat unexpectedly, however, we found that the breeding cultivars
      have the same level of heterozygosity as the landraces. The phylogenetic
      relationships obtained using isozymes among the landraces, synthetic cultivar and
      the cultivars from breeding programs do not reflect their origin. Moreover, the
      cultivar from Brazil is not separated from the remaining populations/cultivars
      studied. However, the data observed using RAPDs and ISSRs are in agreement with
      their known origin. The populations maintained by the farmers in the north of
      Portugal are grouped in a cluster in the phenogram and the C902591 (from Brazil),
      the Alvao (synthetic variety) and Larouco (a hybrid between Montalegre and
      Brazil) are in a different cluster. The ISSRs and RAPDs provide a rapid method
      for the production of polymorphic markers, which appear to correspond to known
      pedigree information.

PMID- 11833287
TI  - Extent and patterns of RAPD variation in landraces and cultivars of rye (Secale
      cereale L.) from northern Europe.
AB  - Little is known about the extent and patterns of distribution of RAPD diversity
      in outcrossing species. This study is the first step in using RAPD markers to
      quantify the amount and distribution of genetic variation within and between
      accessions of 9 landraces and 3 cultivars of cultivated rye from Northern Europe.
      A high level of RAPD variation was detected, demonstrating the utility of RAPDs
      for genetic characterisation in rye. The results show that: (1) landraces and
      improved cultivars maintain roughly the same high levels of RAPD variation, (2)
      landraces from Norway, Germany and Finland showed the lowest level of variation,
      probably because of a small amount of seeds from the original samples, (3) most
      of the RAPD variation was found within rather than between the accessions, which
      is consistent with the pattern expected for a cross pollinated crop. Both the
      cluster and the principal coordinates analyses displayed the same pattern of
      genetic relationship among the accessions studied.

PMID- 11833288
TI  - Synapsis in Robertsonian heterozygotes and homozygotes of Dichroplus pratensis
      (Melanoplinae, Acrididae) and its relationship with chiasma patterns.
AB  - Dichroplus pratensis has a complex system of Robertsonian rearrangements with
      central-marginal distribution; marginal populations are standard telocentric.
      Standard bivalents show a proximal-distal chiasma pattern in both sexes. In
      Robertsonian individuals a redistribution of chiasmata occurs: proximal chiasmata
      are suppressed in fusion trivalents and bivalents which usually display a single
      distal chiasma per chromosome arm. In this paper we studied the synaptic patterns
      of homologous chromosomes at prophase I of different Robertsonian status in order
      to find a mechanistic explanation for the observed phenomenon of redistribution
      of chiasmata. Synaptonemal complexes of males with different karyotypes were
      analysed by transmission electron microscopy in surface-spread preparations. The
      study of zygotene and early pachytene nuclei revealed that in the former,
      pericentromeric regions are the last to synapse in Robertsonian trivalents and
      bivalents and normally remain asynaptic at pachytene in the case of trivalents,
      but complete pairing in bivalents. Telocentric (standard) bivalents usually show
      complete synapsis at pachytene, but different degrees of interstitial asynapsis
      during zygotene, suggesting that synapsis starts in opposite (centromeric and
      distal) ends. The sequential nature of synapsis in the three types of
      configuration is directly related to their patterns of chiasma localisation at
      diplotene-metaphase I, and strongly supports our previous idea that Rb fusions
      instantly produce a redistribution of chiasmata towards chromosome ends by
      reducing the early pairing regions (which pair first, remain paired longer and
      thus would have a higher probability of forming chiasmata) from four to two
      (independently of the heterozygous or homozygous status of the fusion).
      Pericentromeric regions would pair the last, thus chiasma formation is strongly
      reduced in these areas contrary to what occurs in telocentric bivalents.

PMID- 11833290
TI  - The Stockholm populations of Adalia bipunctata (L) (Coleoptera: Coccinellidae)--a
      case of extreme female-biased population sex ratio.
AB  - The genetic composition and sex ratio in the Stockholm populations of Adalia
      bipunctata have been studied. The overall frequency of melanics is 3.2%, which is
      significantly lower than in the populations of St. Petersburg and other large
      cities along the Baltic Sea. The secondary sex ratio in the Stockholm populations
      is female-biased 82:18. More than half of A. bipunctata females are infected with
      the male-killing Spiroplasma bacterium. Beetles of the co-existing species Adalia
      decempunctata are infected with a different bacterium belonging to the genus
      Rickettsia.

PMID- 11833289
TI  - Quantitative genetics of autogamous F2.
AB  - General quantitative genetic properties are derived for the F2 originating from
      self-fertilisation of hybrid (F1) individuals. These results extend and
      generalize previous restricted knowledge about this F2. New equations are found
      for all genotype frequencies, allele frequencies, inbreeding coefficient, genic
      (additive-genetic) and dominance variances, broadsense and narrowsense
      heritabilities, and selection potential. The bulk mean is generally lower, and
      the genotypic variance is generally higher, than those of the F1 and the
      allogamous F2. Genic and dominance variances for the selfed F2 are very different
      to the classical counterparts. Their relationships with inbreeding have been
      investigated, and they are more elaborate than previously considered. The level
      of inbreeding is constant irrespective of parental combinations, which is
      different to the inbreeding of an allogamous F2. Selection potential is generally
      high, and selection advance generally exceeds bulk inbreeding depression. If
      selection is assisted by dispersion, the autogamous F2 may obtain greater genetic
      advance than its allogamous counterpart for the same selection pressure. Under
      conditions of spatially separated F2, swarms, natural selection may be enhanced
      by selfing.

PMID- 11833291
TI  - First evidence of possible outcrossing in the terrestrial slug Arion intermedius
      (Gastropoda: Pulmonata).

PMID- 11833292
TI  - Isolation and characterization of microsatellite markers from the endangered
      Karner blue butterfly Lycaeides melissa samuelis (Lepidoptera).

PMID- 11833293
TI  - Enhanced in vivo IgE production and T cell polarization toward the type 2
      phenotype in association with indoor exposure to VOC: results of the LARS study.
AB  - The association between indoor exposure to volatile organic compounds (VOC),
      prevalence of allergic sensitization and cytokine secretion profile of peripheral
      T cells was studied in 3 year old children of the LARS study (Leipzig Allergy
      Risk Children Study) to investigate the role of VOC exposure as a risk factor for
      the development of atopic disease. Indoor VOC exposure was measured over a period
      of 4 weeks in infants' bedrooms using a passive sampling system. Specific IgE
      antibodies to food, indoor and outdoor allergens were measured by the Pharmacia
      CAP system and correlated to VOC exposure (n = 120). In addition, cytokine
      producing peripheral T cells (interleukin(IL)-4, interferon(IFN)-gamma) were
      measured in a subgroup of 28 children by means of intracellular cytokine
      staining. For the first time we were able to show that exposure to alkanes (C6,
      C9, C10) and aromatic compounds (toluene, o-xylene, m + p-xylene, 2-, 3- and 4
      ethyl-toluene, chlorobenzene) may contribute to the risk of allergic
      sensitization to the food allergens milk and egg white (Odds ratios between 5.7
      and 11.2). Moreover, significantly reduced numbers of CD3+/CD8+ peripheral T
      cells were found in children exposed to alkanes (C9-C13), naphthalene and
      chlorobenzene. Exposure to benzene, ethylbenzene and chlorobenzene was associated
      with higher percentages of IL-4 producing CD3+ T cells. Both an increase in IL-4
      producing type 2 T cells and a reduction of IFN-gamma producing type 1 T cells
      may contribute to a type 2 skewed memory in response to allergens. Therefore, we
      suggest exposure to VOCs in association with allergic sensitization to be
      mediated by a T cell polarization toward the type 2 phenotype.

PMID- 11833294
TI  - "Amalgam disease"--poisoning, allergy, or psychic disorder?
AB  - Frequently, patients in environmental health out-patient units relate various
      complaints to their amalgam fillings. However, an association between the toxic
      exposure and the reported complaints appears plausible only in few cases. We
      investigated toxicological, allergological and psychological parameters in
      patients with amalgam-associated complaints and compared them to controls with
      similar numbers of amalgam fillings. Forty patients with health disturbances
      related to amalgam were compared to a control group without amalgam-associated
      complaints (n = 40), carefully matched for age, sex, and dental status. Mercury
      concentrations were analyzed in blood, saliva, and 24-h-urine. Atopic
      predisposition, determination of IgE, patch testing with amalgam and amalgam
      associated metals and a psychometric assessment were performed in all
      participants. Mercury concentrations in blood or urine were similar in patients
      and controls. Atopic predisposition was markedly enhanced in patients (11/40) as
      compared to controls (5/40). Only one patient with a lichen ruber of the oral
      mucosa showed a contact sensitization to amalgam. Patients reported more psychic
      strain and higher depression scores than controls. Somatization disorders were
      found in 10 patients (25%) and in one control. Eighteen patients (45%) neither
      showed an atopic predisposition nor an influence of psychosocial factors. Toxic
      exposure to mercury does not appear to play a role in "amalgam disease". Since
      many of these patients are atopic without an "amalgam allergy", but with more
      psychic strain and notably more depression, the treatment should be focused on
      allergologic and psychological factors.

PMID- 11833295
TI  - Airborne coagulase negative staphylococci produced by a sewage treatment plant.
AB  - Since some coagulase-negative staphylococci species are involved in clinical and
      environmental situations, the authors carried out a study on the spread of these
      bacteria in the air of a sewage treatment plant. For these purposes a total of
      196 samples were taken from 16 sampling stations, 11 during the day and 5 at
      night (only at 4 points), using the settle plate technique. Altogether 13 species
      of coagulase negative staphylococci were isolated: S. haemolyticus, S. xylosus
      and S. cohnii were particularly common. Station no. 2 (an area almost always kept
      closed containing the fine screens) was found to be the most contaminated. The
      presence of coagulase negative staphylococci was favoured by high temperatures
      and low humidity. No differences were found due to variations in wind speed and
      direction or between day and night.

PMID- 11833296
TI  - Efficacy testing of antimycotic prophylactics in an animal model.
AB  - Trichophyton mentagrophytes is both zoophilic and a common causative organism in
      human dermatomycosis. Therefore this dermatophyte is widely used for experimental
      efficacy testing of antimycotic agents and their active ingredients. The use of
      the guinea pig as an animal model for dermatomycosis is based on the
      predisposition of this species to spontaneous dermal fungal infections. A
      previously described guinea pig model was modified according to the results of
      pilot experiments. The modification consists of 1) evaluation of the infectious
      activity of the primary mycotic tissue cultures obtained from patients and 2) the
      efficacy testing itself with treatment of the infected skin area including the
      continuous clinical observation for 28 days. At first the required duration of
      cultivation and the number of spores for a reproducible infection of all animals
      were determined. The following efficacy test consisted of four groups with ten
      animals each. Group I (control of infection) remained without further treatment
      after experimental infections, groups II-IV received a single treatment by
      spraying at the day of infection with isopropanol (70%) (negative control), water
      (mechanic control) and the antimycotic agent (treated group), respectively. After
      28 days under continuous examination, clinical symptoms (scabs; reddening,
      scaliness) were statistically analyzed. The model takes into account the duration
      and severity of infection in order to evaluate the differences between the four
      groups. The experimental protocol presented allows the efficacy of antimycotic
      agents to be demonstrated by means of statistical analyses. As an example the
      results of a successful prophylactic treatment against T. mentagrophytes with the
      antimycotic prophylactic Laudamonium (1%) are presented.

PMID- 11833297
TI  - A case report of false negative Legionella test results in a chlorinated public
      hot water distribution system due to the lack of sodium thiosulfate in sampling
      bottles.
AB  - We examined samples from the showers and the central water distribution system of
      a public building with an indoor swimming pool. The pool was used for school and
      recreational activities and as a sports therapy facility for patients with
      coronary heart disease. The building's hot water system was contaminated with
      Legionella pneumophila. Due to the building's intricate piping system, several
      attempts to completely eliminate legionellae by thermal and chemical disinfection
      had failed, so an external sanitation company was charged with the installation
      of a continuous chlorination device in order to keep Legionella concentrations
      low. The laboratory which was contracted by the sanitation company to monitor
      bacteria levels after installation of the chlorination device used sampling
      bottles without sodium thiosulfate and repeatedly reported an absence of
      Legionella. However, up to 69,000 colony forming particles (CFP) of Legionella
      pneumophila (Lp) per litre and up to 171 CFP/ml of heterotrophic bacteria could
      be detected when parallel samples were collected in bottles containing sodium
      thiosulfate at standard concentrations. Laboratories, epidemiologists, public
      health officials and technical staff who may be in charge of delivering,
      preparing or using sterile sampling devices for the collection of environmental
      samples to be tested for legionellae should be aware that cultures can return
      false negative results if the sampling containers used to collect chlorinated
      drinking water or chlorinated pool water samples do not contain a neutralizing
      agent to instantly inactivate residual halogen biocides. False negative results
      may lead to a false sense of security regarding the safety of water systems or
      the success of disinfection measures, and may thus endanger public health or even
      hinder the epidemiological clarification of outbreaks.

PMID- 11833298
TI  - Glyoxal is an important allergen for (medical care) cleaning staff.
AB  - While disinfection is essential in medical practice, it carries the risk of
      serious adverse effects, including allergic contact dermatitis. To assess the
      current importance of glyoxal [CAS 107-22-2] as occupational allergen, a
      retrospective descriptive analysis of records of an occupational dermatitis
      clinic in Osnabruck and of national surveillance data of the Information Network
      of Departments of Dermatology (IVDK) in Germany and Austria was performed. Of 189
      highly selected patients with occupational dermatitis tested with glyoxal (1% in
      water or, as trimer, 1% in petrolatum) in Osnabruck, 11 had positive reactions to
      glyoxal, which were occupationally relevant in 9 cases. Causative occupations
      included mainly nursing and room cleaning. In a less selected population of 2626
      additional patients tested in other centres of the IVDK, 40 further positive
      reactions to glyoxal were observed. Concomitant sensitisation to glutardialdehyde
      and formaldehyde, respectively, was frequently observed. In conclusion, glyoxal
      should be tested in all patients with contact dermatitis working in occupations
      with possible exposure to respective disinfecting/cleaning agents.

PMID- 11833299
TI  - Waterborne health risks and the WHO perspective.
AB  - The benefits of improved water and sanitation include both health and non-health
      effects. The direct health benefits are related to two contrasting roles of
      water: that of disease vector when it carries pathogens; and that of health
      mediator through its use in personal and domestic hygiene. Indirect effects
      related to health include for example improved quality of life and decreased
      expenditure on medical expenses. Non-health effects include time savings for
      productive activity or education. The fact that the health impact of inadequate
      water supply services, especially in the developing world, has never been
      established is recognised (Troare, 1992) and recent work highlights unrecognised
      health burdens elsewhere--both from apparently good quality supplies (Payment et
      al., 1991; Payment et al., 1997); and from outbreaks of disease (Ford and
      Colwell, 1996). This paper looks at the WHO perspective on waterborne health
      risks and is divided into three main sections: our knowledge of the existing
      situation; recognised and emerging priorities arising from the changing context;
      and the availability of approaches and tools to meet the recognised and emerging
      priorities.

PMID- 11833300
TI  - [First transplantation of two hands: results after 18 months].
AB  - AIM OF THE STUDY: The previous results achieved in single hand transplantations
      confirmed the feasibility of this procedure and encouraged us to perform the
      first human double hand transplantation, which was performed in January 2000. In
      the present study we reported the results obtained eighteen months after
      transplantation. PATIENT AND METHODS: The recipient was a 33-year old man
      suffering from a traumatic amputation of both hands in 1996. Surgery included
      procurement of the upper extremities from a 18-year old multiorgan cadaveric
      donor, preparation of the graft and recipient's stumps, transplantation of the
      hands, which included bone fixation, arterial and venous anastomoses, nerve
      suture, joining of tendons and muscles, and skin closure. Immunosuppressive
      protocol included tacrolimus, prednisone and mycophenolate mofetil. An intensive
      rehabilitation program was performed. Follow-up included immunological tests,
      skin biopsies, arteriography, bone scintigraphy, electromyography and brain
      functional magnetic resonance imaging. RESULTS: No surgical complications,
      infectious complications and graft-versus-host-disease occurred. Two episodes of
      acute skin rejection were demonstrated and they were completely reversed
      increasing steroid dose. Nerve regeneration and cortical reorganization were
      shown. Sensorimotor recovery was encouraging and life quality improved.
      CONCLUSION: This double hand transplantation showed that conventional
      immunosuppressive protocol is effective and safe as well as that functional
      results are at least as good as those achieved in replanted upper extremities.

PMID- 11833301
TI  - [Code name: "Lindbergh operation"].

PMID- 11833302
TI  - [Mortality from iatrogenic esophageal perforations is high: experience of 54
      treated cases].
AB  - OBJECTIVE: To underline the severity of instrumental esophageal perforations and
      to discuss their management. PATIENTS AND METHODS: Data from patients treated for
      instrumental esophageal perforation were collected retrospectively from 1980 to
      1995 then prospectively since 1995 to 2000. RESULTS: Fifty-four patients were
      treated for instrumental perforations. Perforation occurred after exploratory
      endoscopy (n = 24), endoscopic dilation (n = 13), attempted tracheal intubation
      (n = 5), foreign body extraction (n = 5), treatment of esophageal varices (n =
      4), trans-esophageal echocardiography (n = 2), and duodenal prosthesis
      implantation (n = 1). Clinical manifestations were immediate in 18 cases and
      delayed in all others, with an interval before treatment ranging from 2 hours to
      45 days (mean = 70 hours). All patients were operated after large spectrum
      antibiotherapy and intensive care, except 3 who were treated medically due to
      their poor general condition. Fourteen (26%) patients died, including the 3 non
      operated ones. CONCLUSION: Instrumental esophageal perforations are associated
      with a high mortality, probably due to the poor general condition of the
      patients. Diagnosis of these perforations is often delayed. A good experience of
      endoscopic maneuveurs and adequate post-endoscopic monitoring could allow earlier
      surgical treatment with lower mortality.

PMID- 11833303
TI  - [Treatment of perforated gastroduodenal ulcer by simple suture followed by
      Helicobacter pylori eradication].
AB  - AIMS OF THE STUDY: To determine the prevalence of Helicobacter pylori (HP)
      infection in Vietnam in case of perforated gastro-duodenal ulcer and to evaluate
      efficiency of medical treatment to obtain eradication of HP and ulcer healing.
      PATIENTS AND METHODS: One hundred and eleven patients with perforated gastro
      duodenal ulcer underwent surgical suture. HP infection was diagnosed by urease
      test and pathologic examination of peroperative antral biopsies, and by
      postoperative detection of HP-specific immunoglobulins G. HP infection was
      defined by positivity of at least one test. Medical treatment included
      omeprazole, clarithromycin, and amoxicillin for 7 days followed by omeprazole for
      3 weeks for duodenal ulcer and 5 weeks for gastric ulcer. Follow-up endoscopy
      with biopsies was performed 4 to 6 weeks after treatment cessation. RESULTS:
      Among 111 patients, 107 (96%) were infected by HP. The 4 patients non-infected by
      HP were treated by omeprazole alone and excluded from the study. Ulcer healed in
      99 patients (93%). HP eradication was obtained in 102 patients (95%). The 8
      patients with a non-healed ulcer and the 5 patients in whom HP eradication was
      not obtained at the first endoscopic control received additional medical
      treatment. Ultimately HP eradication and ulcer healing were obtained in all
      cases. CONCLUSION: In a country in which prevalence of HP infection is high, acid
      reduction surgery is unnecessary in case of perforated gastro-duodenal ulcer
      treated by simple surgical closure.

PMID- 11833304
TI  - [Locoregional recurrence of differentiated thyroid cancers: diagnosis-treatment].
AB  - AIM OF THE STUDY: To evaluate the improvement of the diagnosis and the treatment
      of local recurrences (LR) in patients with differentiated thyroid carcinoma.
      MATERIAL AND METHOD: Among a total of 57 patients, two groups were compared:
      group I: 31 patients operated on from 1974 to 1990; group II: 26 patients
      operated on from 1991 to 2000. In the group I, the diagnosis of the cervical
      recurrence was supported by imaging study (ultrasonography, tomodensitometry), in
      the group II by radioiodinescan and serum thyroglobuline (Tg) measurement. The
      main difference was the consideration of Tg measurement to detect the recurrence
      in the group II. A high level of Tg was the only abnormality for 9 patients of
      the group II. RESULTS: A nodal recurrence was respectively present in the group I
      and II in 88.8% and 92% of the cases. Re-operation consisting in thyroid
      totalisation and bilateral lymphadenectomy was respectively performed in 71% and
      100% of the cases. Surgery associated with iodine 131 therapy was respectively
      the treatment for 45.1% and 88.4% of the cases. After a median follow up of 66.2
      months; results of the group I were as follow: normal or undetectable Tg: 10
      (33.3%), second or more cervical recurrences: 7, distant metastases: 11, death in
      relation to thyroid cancer: 11. After a median follow up of 36.3 months, results
      of the group II were as follow: normal or undetectable Tg: 17 (65.4%), second or
      more cervical recurrences: 6, distant metastasis: 5, death in relation to thyroid
      cancer: 1. The best results concerned patients with an isolated elevated Tg
      without anatomical location of the first LR. CONCLUSION: LR diagnosis is
      difficult and needs imaging study, radioiodine-scan and serum Tg determination
      together. Re-operation associated with radioiodine-therapy is the treatment of
      choice. Elevated serum Tg is suffisant to indicate re-operation even if no
      anatomical substrate is found. Iodine-radiotherapy alone is generally unable to
      obtain undetectable serum Tg.

PMID- 11833305
TI  - [Interest in intestinal resection for treatment of advanced ovarian cancer].
AB  - AIM OF THE STUDY: Digestive surgery is often necessary for surgical management of
      advanced ovarian carcinoma. PATIENTS AND METHODS: In a series of 62 patients with
      stage III ovarian carcinoma, postoperative morbidity and mortality, overall
      survival after 5 years and disease-free survival after 2 years were studied and
      corelated with several patients criteria (age, stage of the disease, residual
      disease, type of surgery, CA125 normalisation delay, postoperative complications
      and hospital stay). Patients were divided into two groups according to the
      surgical treatment. The first group (n = 17) included patients treated by
      gynecologic and digestive surgery, the second group (n = 45) included patients
      treated by gynecologic surgery only. All patients were proposed for chemotherapy
      included platyn salt. Mean age was 60 years (range: 20-83). The stage of the
      cancer was stage IIIa in 7 cases, stage IIIb in ten and stage IIIc in 45.
      RESULTS: Postoperative mortality was 3.5% (2/62). Postoperative morbidity was 26%
      (13/62). No statistical differences were noted for hospital stay, general
      morbidity, surgical morbidity when a gastric resection or a colon resections or a
      splenectomy were performed. Overall survival at 5 years was 56%. Residual disease
      less than 2 cm3 is the only prognostic factor for overall survival (56% vs 23% [P
      = 0.03]) and disease-free survival (86% vs 46% [P = 0.02]). CONCLUSION: This
      study including 62 patients confirmed the prognostic significance of extensive
      cytoreductive surgery for treatment in advanced ovarian epithelial cancer without
      increasing the postoperative morbidy and mortality.

PMID- 11833307
TI  - [Hand transplantation?].

PMID- 11833306
TI  - [Medial pancreatectomy: results of a series of 11 patients].
AB  - AIM OF THE STUDY: To report a new series of medial pancreatectomy (MP), with
      analysis of early and long-term results. PATIENTS AND METHODS: From 1990 to 1999,
      11 patients (mean age = 53 years, extremes: 28-70)--including 10 non-diabetic-
      underwent MP for neuroendocrine tumor (n = 5), intraductal papillary mucinous
      tumor (IPMT) (n = 3), serous cystadenoma, metastasis from renal cell carcinoma,
      and focal pancreatitis. The procedure included medial resection of variable
      extent, frozen section, and suture of the cephalic stump. The caudal stump was
      either anastomosed to the posterior gastric wall (n = 9), or closed when atrophic
      or very small (n = 2). RESULTS: The mean length of resection was 7 cm (extremes:
      4-15). The diagnosis suspected preoperatively was confirmed in 10 cases. In one
      patient, a suspected adenocarcinoma was actually a focal pancreatitis. No
      postoperative death occurred. Seven patients experienced complications: one
      delayed gastric emptying and 6 pancreatic fistulas (54%), including 3 associated
      with intraabdominal collection. Two patients were reoperated to drain a
      pancreatic fistula. The mean hospital stay was 14 days (extremes: 10-21) without
      complications, and 30 days (extremes: 11-90) after complications. After a mean
      follow-up of 45 months (extremes: 7-130), only one patient initially non-diabetic
      experienced post-operative diabetes and needs enzyme therapy after a 15 cm
      resection for IPMT. No patient developed isolated intrapancreatic recurrence.
      CONCLUSIONS: MP preserves efficiently pancreatic function and is associated with
      a low risk of intrapancreatic recurrence. Conversely, MP is associated with an
      high risk of pancreatic fistula.

PMID- 11833308
TI  - [Angiosarcoma of the breast: a case report].
AB  - We report a breast's angiosarcoma case admitted at the maternity hospital Souissi
      of Rabat in 1997. We discussed epidemiologic, diagnostic and therapeutic aspects
      of this type of tumor insisting on the difficulties of diagnosis.

PMID- 11833309
TI  - [CT scan diagnosis of colo-colic intussusception due to a lipoma of the left
      colon].
AB  - We report the case of a 27 years-old man with a left colo-colic intussuception
      due to a lipoma. CT scan allowed diagnosis of the obstruction, of the
      intussuception and showed his cause as an intraluminal fatty mass in the left
      colic angle, typical of lipoma. Resection of the mass was performed and mature
      fat cells were identified microscopically.

PMID- 11833310
TI  - [Diaphragmatic hernia after esophagectomy: 2 case reports and review of the
      literature].
AB  - Diaphragmatic herniation of is uncommon after esophagectomy. The aim of this
      study was to report two cases of transhiatal herniation following esophagectomy,
      to analyse the contributing factors of this complication and to expose the
      preventive treatment, by means of a review of the literature.

PMID- 11833311
TI  - [Cicatrix endometriosis of the abdominal wall].
AB  - Endometriosis is a rare entity, related after operation on the uterus or uterine
      tubes or a laparotomy procedures or other extrapelvic procedures, when seeding of
      endometrial fragments were shed into the peritoneal cavity. We report the case of
      a menopaused woman with a subcutaneous incisional scar mass that appeared 22
      years after a caesarean section. The diagnosis was made by histological
      examination.

PMID- 11833312
TI  - [Identification of recurrent inferior laryngeal nerve during a thyroid
      lobectomy].
AB  - Based an their findings during thyroid operations and pathological examination of
      100 specimens, the authors report the principal steps for identification and
      dissection of recurrent nerve during a thyroid lobectomy.

PMID- 11833313
TI  - [Helical computed tomography in the diagnosis of acute appendicitis].

PMID- 11833314
TI  - [Surgical treatment for Crohn's disease].
AB  - Surgery is mandatory in most patients with Crohn's disease. Crohn's disease
      refractory to medical treatment represents the main indication for surgery. After
      intestinal resection, the patient remains exposed to a high risk of recurrence on
      the remnant bowel. It is the reason why, firstly, intestinal resection for
      Crohn's disease should be performed without extended resections margins,
      secondly, it must be restricted to symptomatic lesions, and thirdly, prophylactic
      therapy should be given postoperatively. The laparoscopic approach is to date
      more an more proposed in patients with Crohn's disease. It could be the procedure
      of choice for elective ileocaecal resection. Its use in emergency situations and
      for more large resections, such as total colectomy followed by ileorectal
      anastomosis is still under evaluation.

PMID- 11833315
TI  - [Laparoscopic choledocholithotomy. Indications and methods of completion].
AB  - Modern views on diagnostic and medical algorithm using mini-invasive technologies
      for complicated cholelithic disease (CHLD) were summarized. Main indications and
      methods of the laparoscopic choledocholithotomy completion in 71 patients with
      choledocholithiasis were presented. Original, elaborated in the clinic methods
      were presented along with conventional diagnostic methods. Introduction of the
      proposed diagnostic-medical complex had permitted to improve the results of
      planned and urgent operations for complicated CHLD.

PMID- 11833316
TI  - [Injury of biliary ducts in laparoscopic cholecystectomy].
AB  - Peculiarities of the biliary ducts (BD) damage while performance of laparoscopic
      cholecystectomy (LCHE) and their significance in the choice of the operative
      correction method were studied up. In 35 patients the kinds and mechanisms of BD
      damage were analyzed. Taking into account large and small injuries, the general
      frequency of BD trauma while performance of LCHE had constituted 0.11%, what is
      comparable with indexes, characteristic for open cholecystectomy. Electric burn
      of BD wall, isolated one or in conjunction with other kinds of trauma, were
      observed in 15 (42.8%) of patients. Miniinvasive interventions, including those
      using laparoscopic access, are effective in treatment of small and some kinds of
      partial injuries. The operation of choice in correction of BD damage is formation
      of high hepaticojejunoanastomosis, when diagnosis is established intraoperatively
      or was postponed.

PMID- 11833317
TI  - [Aspects of diagnosis and choice of surgical strategies in patients with Mirizzi
      syndrome].
AB  - Problems of diagnosis and surgical treatment of Mirizzi syndrome (MS) were
      suggested, basing on analysis of examination and treatment of 78 patients. There
      was presented experience of successful laparoscopic treatment of some kinds of
      MS.

PMID- 11833318
TI  - [Diagnosis and treatment of cystic transformation of biliary ducts].
AB  - Experience of surgical treatment of 58 patients with cystic transformation of
      biliary ducts of various type was presented. There were adduced tactics of
      examination of the patients, kinds of operative treatment, postoperative
      complications were analyzed. In 33 patients there was performed resection of
      cystically-changed common biliary duct and subsequent formation of
      hepaticojejunoanastomosis with the jejunal loop, excluded according to Roux
      method. Late results of treatment of patients were studied. Malignization in
      cystic wall was revealed in 2 (3.4%) of patients. One patient died.

PMID- 11833319
TI  - [Diagnoses and treatments by transcutaneous transhepatic approach in patients
      with obstructive jaundice].
AB  - In 298 patients with obstructive jaundice, including 271 (90.9%) with tumoral
      genesis, endobiliary interventions were performed: transcutaneous transhepatic
      cholecystectomy--in 76, external cholangiostomy--in 155, external-internal
      cholangiostomy--in 97, endoprosthesis of biliary ducts (BD)--in 23. Of 155
      patients, to whom external drainage of BD was done, recanalization of obstructed
      portion was performed in 53. Of 102 patients, to whom external drain was
      adjusted, in 23.1% the complications occurred. Hospital mortality had constituted
      22%. The BD perforation was noted in 8 observations. The patients life span, in
      whom the external-internal BD drainage was done, was 7.8 months, an efficacy of
      endoprosthesis had constituted 97.3%. The life span of such patients was (9.2 +/-
      2.4) months at average.

PMID- 11833320
TI  - [The application of extracorporeal shock-wave lithotripsy in the treatment of
      choledocholithiasis].
AB  - The method of extracorporal shockwave biliary lithotripsy was introduced in the
      clinic since 1993 yr in patients with residual choledocholithiasis. The method
      was applied in 25 patients. Cholecystectomy with external drainage of common
      biliary duct was performed in all patients beforehand. Positive result was noted
      in 16 observations. All patients are alive.

PMID- 11833321
TI  - [Application of mini-invasive technologies in treatment of chronic biliary
      pancreatitis].
AB  - Results of examination and treatment of 609 patients with chronic biliary
      pancreatitis (CHBP), caused by various forms of cholelithic disease,
      papillostenosis, cystic transformation of biliary ducts, were analyzed. There
      were applied open, laparoscopic and endoscopic methods of treatment. Diagnostic
      algorithm was elaborated, which proved its trustworthiness in 92% of
      observations. There were established possibilities and advantages of miniinvasive
      technologies in the treatment of CHBP, expediency of their usage to reduce the
      hospital stay duration and frequency of complications, to improve the quality of
      life of the patients. Application of minitraumatical methods had permitted to
      avoid mortality.

PMID- 11833322
TI  - [Application of electro-thermo-adhesion in hepatobiliary surgery].
AB  - Since 1999 yr. 283 laparoscopic operations were performed in the clinic for
      diseases of liver, biliary ducts, pancreas using electrothermoadhesion method,
      including 201 cholecystectomies, 62--in presence of hepatic cyst, 6--enucleation
      of hemangioms, 3--hepatic edge resection, 1--cholecystectomy, in 10 patients the
      puncture biopsy of pancreas was done.

PMID- 11833323
TI  - [Transcutaneous interventions under the ultrasonographic investigation control of
      organs of hepato-pancreatic-biliary zone].
AB  - Results of treatment of some surgical diseases of the hepatopancreatoduodenal
      zone organs using transcutaneous intervention under the ultrasonic investigation
      control were analyzed. There were confirmed their high efficacy in the treatment
      of focal purulent diseases, hepatic cyst, possibility of application as primary
      surgical manipulation in treatment of destructive forms of an acute pancreatitis
      and in external drainage of biliary ducts for obstructive jaundice. Perspective
      trends of the method usage were determined.

PMID- 11833324
TI  - [Mini-invasive endovascular procedures in patients with complicated portal
      hypertension].
AB  - Experience of application of endovascular methods of treatment of complicated
      portal hypertension--embolization of hepatic, splenic and left gastric arteries-
      was summarized, their efficacy was estimated, indications to their conduction was
      substantiated. Most effective method of endovascular treatment of patients with
      complicated portal hypertension is durable parenchymatous--truncular embolization
      of splenic artery.

PMID- 11833325
TI  - [Roentgeno-endovascular surgery of tumoral and traumatic injuries of the liver].
AB  - In 17 patients with primary and metastatic hepatic cancer there was performed
      roentgenoendovascular occlusion (REO) of a. hepatica propria using fine disperse
      embolizing substances. In 30 patients regional infusion therapy (RITH) was
      conducted using preparations of platinum. In 11 patients REO was performed, and
      than--RITH. Chemical embolization of a. hepatica propria using cisplatinum in 200
      mg dose, suspensed in 12 ml of mayodil or ethiotrast was done in 12 patients. The
      survival index for patients, to whom REO was conducted, had constituted at
      average (15.3 +/- 3.3) months, RITH--(14.4 +/- 2.6) months, REO and RITH--(20.6
      +/- 3.2) months, chemical embolization--(18.3 +/- 1.5) months. REO of a. hepatica
      propria was conducted also to the patients with posttraumatic hemobilia. Of 16
      examined patients REO using polyurethane emboli 2-2.5 mm in diameter was
      conducted in 14, in 2 trans-hepatic injection of ethanol in the pseudoaneurysm
      cavity was applied. Hemorrhage was stopped in all the patients. In 1 patient in 3
      months after REO conduction recurrency occurred, which was eliminated by repeated
      REO. REO of tumoral and traumatic hepatic affection constitutes an effective
      miniinvasive method when operative intervention is ineffective or not possible to
      perform.

PMID- 11833326
TI  - [Experimental elaboration and perspectives of application of electric welding of
      the live tissues].
AB  - In experiment on pigs, rabbits and white rats there was examined method of
      electric welding (electrothermoadhesion) of live tissues--intestine, stomach,
      gallbladder and bladder, peritoneum, elements of mesentery, liver, spleen. We
      distinguish among "welding" of the hollow organs wall with restoration of their
      passability and "overwelding" of masses of the tissues with production of
      coagulational furrow, along which resection of necessary parts is executed.
      According to data of morphological investigations obtained the security of the
      method was established. Peculiarities of welding suture of tissues were studied.
      The method is introducing in the clinical practice actively due to its simplicity
      and safety in sutureless connection of tissues.

PMID- 11833327
TI  - [Mini-invasive methods of treatment of choledocholithiasis].
AB  - Last years in the clinic in diagnosis and treatment of choledocholithiasis
      choledochofibroscopy is applied widely while performing an open or laparoscopic
      intervention and while introduction of choledochoscope through external biliary
      fistula as well. Best results were achieved in those patients, in whom it was
      possible to evacuate all concrements through ductus cysticus. Introduction of
      biliary stent have permitted to perform clippage of ductus cysticus without
      making external drainage, securing rapid rehabilitation of patients.

PMID- 11833328
TI  - [Restoration of colonic continuity after the Hartmann's surgery].
AB  - The intestinal continuity restoration after performance of Hartmann's operation
      in presence of long rectal stump was done using the method of the duplicature
      anastomosis formation, which was elaborated in the clinic. The frequency of
      postoperative complications occurrence was 9.8%: In presence of short rectal
      stump the colon was descended on perineum via submucosal tunnel in rectal stump
      according to the method, which was elaborated in the clinic. The frequency of the
      postoperative complications occurrence was 16.7%. The data presented trusts the
      expediency of application of the methods elaborated in the clinic for restoration
      of intestinal continuity after performance of Hartmann's operation in presence of
      long and short rectal stumps.

PMID- 11833329
TI  - [The choice of ventroplasty method using local tissues for postoperative large
      abdominal hernia].
AB  - Experience of treatment of 355 patients with large, gigantic, complex
      postoperative abdominal hernia, operated in the planned order in 1983-2000 yrs,
      is presented. Ventroplasty, using tissues of patients of their own, was done in
      all the patients. The one-stage, staged, T-like plasty was done, the hernial sac
      plasty, methods of trebled, quadrypled and increased sixfold were performed as
      well. The abovementioned ventroplasty methods application have permitted to
      eliminate the defects in musculoaponeurotic layer of abdominal wall of any size,
      localization and compexity. Immediate and late result was favourable. Mortality
      had constituted 0.6% (two patients died). Absence of hernial recurrency for
      follow-up to 17 years in 95.8% patients trusts efficacy of these methods of
      treatment and makes possible to recommend them for application in clinical
      practice.

PMID- 11833330
TI  - [Lessons on laparoscopic cholecystectomy (summary of the experience].
AB  - The experience of laparoscopic cholecystectomy conduction in 6524 patients with
      nontumoral diseases of gallbladder (chronic calculous cholecystitis, an acute
      calculous cholecystitis, chronic noncalculous cholecystitis, the gallbladder
      polyposis) was summarized. While comparing the initial seizing experience in
      laparoscopic cholecystectomy in the clinic the tendency was noted, trusting the
      skills improvement in management of laparoscopic technique, permitting to reduce
      the contraindications quantity for laparoscopic cholecystectomy. Several
      principles were elaborated, which is necessary to follow doing laparoscopic
      cholecystectomy for improvement of results of treatment in patients and for
      complications reduction.

PMID- 11833331
TI  - [Technical aspects of one stage reconstruction of mammary glands using autologous
      tissue after mastectomy for the mammary gland cancer].
AB  - In 36 patients the first experience of performance of one-stage mammarial glands
      reconstruction is presented, using tissues of their own after conduction of
      mastectomy for the mammarial gland cancer. In 27 women patients the transposition
      or free microvascular transplantation of lower musculocutaneous flap basing on m.
      Rectus abdominis (transverse rectus abdominis musculocutaneous TRAM-flap) was
      performed, in 9--transposition of m. Latissimus dorsi flap.

PMID- 11833332
TI  - [Kinetics of mitotic rhythmic activity in oat (Avena sativa) coleoptiles
      following irradiation].
AB  - The analysis of different intensity (10-200 Gy) irradiation influence on
      rhythmical processes in mitotic activity of oats coleoptiles was carries out.
      Obtained results indicate that irradiation disorders phase and amplitude of the
      cell division rhythm in investigated material. This disturbance, as judged by
      doze dependence, is associated with unknown molecular structures.

PMID- 11833333
TI  - [Aneuploid model of meiotic transformation mechanisms in wheat. 1. Mechanism of
      chromosome shift from mitosis to meiosis].
AB  - A model of chromosome shift from mitosis to meiosis based on analysis of
      univalent behavior in meiotic anaphase I in the complete series of monosomic
      lines of Milturum 553 wheat cultivar is proposed. According to the model,
      chromosomes of homologous pairs change their pole orientation by two different
      mechanisms. Such co-orientation is achieved through segregation of initial pole
      zone in one haploid set and through synapsis of homologues in the other.

PMID- 11833334
TI  - [Aneuploid model of meiotic transformation mechanisms in wheat. 2. Prevention of
      homologue synapsis].
AB  - Two main elements of the mechanism of preventing the homoeologue synapsis were
      revealed using statistical analysis of the univalent behavior in meiotic anaphase
      I in the whole series of monosomic lines of wheat cultivar Milturum 553. One of
      the elements was found to be controlled by chromosomes 1B, 3B and 6A, and the
      latter being equally effective in both double and single doses.

PMID- 11833336
TI  - [Genetic control of the isoenzymes in Cembra pine (Pinus cembra L.) in the
      Ukrainian Carpathian Mountains].
AB  - Genetic control of GOT, GDH, DIA, MDH, SOD, FDH, ADH, ACP, and LAP enzymes was
      studied in the seed megagametophytes of cembra pine (Pinus cembra L.) from the
      natural population of the Ukrainian Carpa-thian mountains. Efficient
      electrophoretic separation was obtained for 21 loci products. The analysis of
      allele segregation in heterozygous trees confirms monogenic inheritance of the
      revealed variants.

PMID- 11833335
TI  - [Molecular and genetic polymorphism in three cattle breeds].
AB  - Determination of cattle breed and assignment of individual animals to that or
      another group based on distinctions of genotype is of great importance in
      genetics and selection. Using of PCR-analysis opened new possibilities for typing
      DNA. The procedure of PCR was optimized for animal DNA. Two methods of PCR, RAPD
      and SSRP, were applied for investigation of molecular-genetical polymorphism in
      three cattle breeds (Ukrainian red-motley lactescent, Golshtine and Simmental). A
      dendrogram reflecting genetical mutual relations between analyzed animals was
      drawn. The level of homo-heterozygosity and the distribution of microsatellite
      alleles were determined. System for investigation of molecular-genetical
      polymorphism in the cattle breeds and characterization of genotype of individual
      animals were developed and tested on a real population.

PMID- 11833337
TI  - [Supernumerary chromosomes in the karyotype of the Siberian spruce, P. obovata].
AB  - Results of karyological study of ornamental forms of Picea obovata Ledeb. are
      presented. Typical chromosome number (2n) is 24, but some trees have one or two
      additional chromosomes (2n = 24 + 1B; 2n = 24 + 2B). Heritability of additional
      chromosomes, pollen fertility, morphological features of cones, and seed quality
      in trees with and without additional chromosomes were studied. System of B
      chromosomes is of importance for population and species adaptation and possibly
      plays a role in adaptation of P. obovata under introduction.

PMID- 11833338
TI  - [Manifestation of "hairy leaf" trait in mangel beet].
AB  - New morphological trait, "Hairy leaf", of mangel beet has been picked out.
      Dominant character and monogenic inheritance of the trait were found. Comparative
      analysis of manifestation of this trait in mangel and sugar beets was done. It is
      shown that the gene of "hairiness" (Hl) in sugar beet is not allelic to the Hlvar
      gene in mangel beet. This trait can be used as a marker in selection-genetical
      investigation.

PMID- 11833339
TI  - [Frequency of stable chromosomal aberrations determined by FISH in 49 Chernobyl
      nuclear accident liquidators exposed to various doses of radiation].
AB  - FISH technique was tested on the 49 liquidators of the Chernobyl Accident. Groups
      were formed according to average group exposure doses and/or individual ones
      determined by the method of EPR. The essential variability of spontaneous and
      irradiation-induced frequencies of reciprocal translocations was observed. In
      groups with the lowest EPR-doses (below 25 cGy) the average cytogenetic dose was
      considerably higher then doses determined by EPR-method. The best coincidences
      between average in-group EPR- and FISH-doses were in the group with 25-50 cGy
      doses for "acute irradiation" model and in the group with 50-100 cGy and higher
      for "chronic irradiation" model.

PMID- 11833340
TI  - [Dose curves for radiation-induced cytogenetic damage in human lymphocytes].
AB  - Insufficient fitness of experimental data with convenient linear and linear
      quadratic models of "dose-effect" dependence for the number of chromosome
      aberrations of different types were revealed. Proposed method of approximation of
      the experimental "dose-effect" dependence with piece-linear splines allows to
      obtain more accurate results in the most cases and therefore is more preferable
      than the linear and linear-quadratic models.

PMID- 11833342
TI  - Preparation of recombinant plant calmodulin isoforms.

PMID- 11833341
TI  - [Locus Delta in the Notch signaling system: organization and pleiotropic function
      during Drosophila development].
AB  - Delta locus is the important component of the Delta-Notch signaling system
      implicating in a general mechanism of local cell signaling. Delta and Notch
      encode the evolutionary conserved cell surface proteins that interact and
      function as ligand (DELTA) and receptor (NOTCH) in a wide variety of cell fate
      specification events during oogenesis, embryogenesis and metamorphosis.

PMID- 11833343
TI  - Isolation of recombinant cardiac troponin C.

PMID- 11833344
TI  - Skeletal muscle troponin C. Expression and purification of the recombinant intact
      protein and its isolated N- and C-domain fragments.

PMID- 11833345
TI  - Purification of recombinant calbindin D9k.

PMID- 11833346
TI  - S100 proteins. From purification to functions.

PMID- 11833347
TI  - Cadherins.

PMID- 11833348
TI  - Calcium.
AB  - This chapter describes the chemical and biological value of the calcium ion. In
      calcium chemistry, our main interest is in equilibria within static, nonflowing
      systems. Hence, we examined the way calcium formed precipitates and complex ions
      in solution. We observed thereafter its uses by humankind in a vast number of
      materials such as minerals, e.g., marble, concrete, mortars, which parallel the
      biological use in shells and bones. In complex formation, we noted that many
      combinations were of anion interaction with calcium for example in the uses of
      detergents and medicines. The rates of exchange of calcium from bound states were
      noted but they had little application. Calcium ions do not act as catalysts of
      organic reactions. In biological systems, interest is in the above chemistry, but
      extends to the fact that Ca2+ ions can carry information by flowing in one
      solution or from one solution to another through membranes. Hence, we became
      interested in the details of rates of calcium exchange. The fast exchange of this
      divalent ion from most organic binding sites has allowed it to develop as the
      dominant second messenger. Now the flow can be examined in vitro as calcium binds
      particular isolated proteins, which it activates as seen in physical mechanical
      changes or chemical changes and this piece-by-piece study of cells is common.
      Here, however, we have chosen to stress the whole circuit of Ca2+ action
      indicating that the cell is organized both at a basal and an activated state
      kinetic level by the steady state flow of the ion (see Fig. 11). Different time
      constants of exchange utilizing very similar binding constants lead to: 1) fast
      responses as in the muscle of an animal; or 2) slower change as in
      differentiation of an egg or seed. Many other changes of state may relate to Ca2+
      steady-state levels of flow in the circuitry and here we point to two: 1)
      dormancy in reptiles and animals; and 2) sporulation in both bacteria and lower
      plants. In the other chapters of this volume many components of the overall
      circuitry will be described. The reader should try to marry these into the
      overall activity of the cell for on top of molecular biology there is the
      cooperative system molecular biology of cells. To give an analogy, whereas much
      can be understood from the analysis of the properties of single-isolated water
      molecules, even examining their interaction in ice, this study alone cannot lead
      to an appreciation of the melting or boiling points of bulk water.

PMID- 11833349
TI  - Alpha-lactalbumin and (calcium-binding) lysozyme.

PMID- 11833350
TI  - Recombinant annexin II tetramer.

PMID- 11833351
TI  - Purification and characterization of ALG-2. A novel apoptosis-linked Ca(2+)
      binding protein.

PMID- 11833352
TI  - Crystallization and structural details of Ca(2+)-induced conformational changes
      in the EF-hand domain VI of calpain.

PMID- 11833354
TI  - Crystallization and structure-function of calsequestrin.

PMID- 11833353
TI  - Neurocalcin. Role in neuronal signaling.

PMID- 11833356
TI  - Calcium-binding proteins.

PMID- 11833355
TI  - Use of fluorescence resonance energy transfer to monitor Ca(2+)-triggered
      membrane docking of C2 domains.

PMID- 11833357
TI  - Ca(2+)-binding mode of the C2A-domain of synaptotagmin.

PMID- 11833358
TI  - Study of calcineurin structure by limited proteolysis.

PMID- 11833359
TI  - Crystal structure of calpain and insights into Ca(2+)-dependent activation.

PMID- 11833360
TI  - The multifunctional S100 protein family.

PMID- 11833361
TI  - Ca2+ binding to proteins containing gamma-carboxyglutamic acid residues.

PMID- 11833362
TI  - The caseins of milk as calcium-binding proteins.

PMID- 11833364
TI  - Memoirs reflect CHA leadership model core competencies.

PMID- 11833363
TI  - Reclaiming our values: lessons from tragedy.

PMID- 11833365
TI  - Broad campaign with simple message can reap great results.

PMID- 11833367
TI  - Reforming the health care structure. Physicians and hospital leaders must come
      together in a genuine partnership.

PMID- 11833366
TI  - Does Catholic sponsorship matter? Social science is beginning to reveal
      differences between the ministry and other forms of care.

PMID- 11833368
TI  - Mission integration in Wisconsin. A Chippewa Falls hospital works to turn
      employees into "servant leaders".

PMID- 11833369
TI  - Niche services. Fifth in a series examining revenue growth strategies in a
      difficult health care market.

PMID- 11833370
TI  - For an ethics of technology. A science that violates the established order of
      reality could prove to be disastrous.

PMID- 11833371
TI  - Care and cultivation. Protestant thinking on biotechnology seeks a balance
      between freedom and responsibility.

PMID- 11833372
TI  - Setting moral limits on technology. The Jewish perspective differs in some ways
      from Catholic and Protestant ones.

PMID- 11833373
TI  - The technology trap. Our American love for medical gadgetry blinds us to its
      hidden costs.

PMID- 11833374
TI  - Humane long-term care: a "product" always in demand.

PMID- 11833375
TI  - Confronting the tyranny of conventional wisdom.

PMID- 11833377
TI  - Picking up speed. Healthcare spending growth fastest in 12 years.

PMID- 11833378
TI  - Score one for hospitals. N.Y. AG losing battle to two affiliating facilities.

PMID- 11833376
TI  - Striking a balance. Thompson says he'll include consumer groups in regulatory
      reform task force.

PMID- 11833379
TI  - Bonus time. California association plans to reward physicians for good patient
      care.

PMID- 11833380
TI  - Fewer hospitals close doors in '01.

PMID- 11833381
TI  - Hitting the brakes. Hospital merger-and-acquisition activity declines for third
      consecutive year.

PMID- 11833382
TI  - 2001 mergers and acquisitions (1 of 6).

PMID- 11833383
TI  - Into the deep. Vandewater may buy Alabama not-for-profits.
AB  - After a few years of lying low since resigning from Columbia/HCA amid a massive
      federal fraud probe, former President and COO David Vandewater is back in the
      thick of things with a new company and a deal to purchase not-for-profit
      hospitals.

PMID- 11833384
TI  - Rx for nurses. Final version of staffing legislation in the works.

PMID- 11833385
TI  - Pa. dispute heats up. UPMC considers selling in-house health plan.

PMID- 11833386
TI  - Paperwork, paperwork. New extension on HIPAA comes with strings.

PMID- 11833387
TI  - Outlook '02.

PMID- 11833388
TI  - Improving care through integration.

PMID- 11833389
TI  - Payment due. Report: CMS slacker for not collecting millions.

PMID- 11833390
TI  - Getting concrete on paperwork. Thompson, Scully set to try to make good on
      promise of regulatory relief.
AB  - Too much paperwork, not enough time. For providers, it may come with the
      territory, but there may be relief in sight. HHS' new Advisory Committee on
      Regulatory Reform will take up the prickly problem as the latest battle to
      unburden the healthcare industry from needless distractions gears up.

PMID- 11833391
TI  - Does divorce hurt kids?

PMID- 11833392
TI  - The ultimate sacrifice.

PMID- 11833393
TI  - The Yates odyssey.

PMID- 11833394
TI  - Perceptions of level I and level II fieldwork in the same site.
AB  - Perceptions of the Same Site Model (SSM) of fieldwork, where students complete a
      Level I and Level II fieldwork requirement in the same setting, were examined by
      survey. The benefits, drawbacks, and implications of the SSM are discussed.
      Fieldwork educators and students identified gaining familiarity with the setting,
      increased comfort and decreased anxiety, and preparation for Level II fieldwork
      as benefits of this model. The SSM survey results suggest that this model may be
      helpful in decreasing stress associated with fieldwork as experienced by students
      and fieldwork educators.

PMID- 11833395
TI  - The future of electronic aids to daily living.

PMID- 11833396
TI  - Attempting to use a Cochrane review: experience of three occupational therapists.

PMID- 11833397
TI  - Effectiveness of school-based occupational therapy intervention on handwriting.
AB  - OBJECTIVE: This study investigated the effects of school-based occupational
      therapy services on students' handwriting. METHOD: Students 7 to 10 years of age
      with poor handwriting legibility who received direct occupational therapy
      services (n = 29) were compared with students who did not receive services (n =
      9) on handwriting legibility and speed and associated performance components.
      Visual-motor, visual-perception, in-hand manipulation, and handwriting legibility
      and speed were measured at the beginning and end of the academic year. The
      intervention group received a mean of 16.4 sessions and 528 min of direct
      occupational therapy services during the school year. According to the
      therapists, visual-motor skills and handwriting practice were emphasized most in
      intervention. RESULTS: Students in the intervention group showed significant
      increases in in-hand manipulation and position in space scores. They also
      improved more in handwriting legibility scores than the students in the
      comparison group. Fifteen students in the intervention group demonstrated greater
      than 90% legibility at the end of the school year. On average, legibility
      increased by 14.2% in the students who received services and by 5.8% in the
      students who did not receive services. Speed increased slightly more in the
      students who did not receive services. CONCLUSION: Students who received
      occupational therapy services demonstrated improved letter legibility, but speed
      and numeral legibility did not demonstrate positive intervention effects.

PMID- 11833398
TI  - Testing the effect of kinesthetic training on handwriting performance in first
      grade students.
AB  - OBJECTIVE: The purpose of this study was to investigate the effect of kinesthetic
      training' on handwriting performance in first-grade students 6 to 7 years of age
      who had kinesthetic deficits and handwriting difficulties. METHOD: With a
      randomized-blinded three group research design, 45 children were assigned to
      either a kinesthetic training group, a handwriting practice group, or a no
      treatment group. Kinesthesis and handwriting legibility were measured before and
      after intervention. Teachers' judgments of handwriting legibility in the
      classroom setting were sought at 4 weeks after the intervention to see whether
      any improvement gained would be maintained in the natural setting. Two-way
      repeated-measures analysis of variance was used for data analyses. RESULTS: At
      posttest, all groups showed significant improvement of kinesthesis, with no
      significant difference in the magnitude of improvement among the groups. There
      was no significant improvement of handwriting legibility as measured by a
      standardized test in any of the groups, although teachers indicated improvement
      of handwriting legibility in the classroom setting in all groups. Teachers also
      reported maintenance of handwriting legibility at 4 weeks after posttest.
      CONCLUSION: Kinesthetic training did not improve handwriting or kinesthesis in
      these children. The findings of this study offer no support for use of
      kinesthetic training to improve handwriting legibility in first-grade students.

PMID- 11833399
TI  - Relationships between handwriting and keyboarding performance of sixth-grade
      students.
AB  - OBJECTIVES: This study examined the relationships between sixth-grade students'
      handwriting speed and legibility and their keyboarding speed and error rate. A
      second purpose was to examine how well handwriting performance discriminates
      students as slow or fast in computer keyboarding. METHOD: After participation in
      a school-required keyboarding class, 40 sixth-grade students were asked to copy a
      familiar poem using handwriting and keyboarding. Handwriting legibility and speed
      and keyboarding speed and errors were measured. Relationships among these
      variables were analyzed using Pearson product-moment correlations and
      discriminant analysis. RESULTS: Keyboarding speed correlated with handwriting
      legibility (n = 38, r = .361, p = .026), suggesting that handwriting performance
      accounts for 12% to 13% of the variance in keyboarding performance. Handwriting
      speed and legibility together accurately categorized 71% of students as slow or
      fast in keyboarding. On average, students were able to keyboard faster than
      handwrite. Of the 20 slowest handwriters, 75% achieved more text production with
      keyboarding than with handwriting. CONCLUSION: Keyboarding performance
      demonstrated low to moderate correlation with handwriting performance, suggesting
      that these forms of written expression require distinctly different skills. Most
      students who were slow at handwriting or had poor legibility increased the
      quantity and overall legibility of text they produced with a keyboard. These
      results suggest that keyboarding has the potential to increase and improve a
      student's written output.

PMID- 11833400
TI  - Pragmatism and structuralism in occupational therapy: the long conversation.
AB  - The history of occupational therapy may be understood as a continual transaction
      between two cultural discourses: pragmatism and structuralism. Pragmatism is a
      way of thinking that presupposes humans are agentic by nature and knowledge is
      tentative and created within particular contexts. Structuralism is a way of
      thinking that assumes humans are composites of recurring general frameworks and
      that knowledge is objective and can be generalized to multiple contexts. Early in
      the field's history, both pragmatist and structuralist assumptions about the
      human and knowledge produced different readings, or interpretations, of what
      constituted the appropriate tools, methods, and outcomes for occupational
      therapy. Consequently, occupational therapy adopted an interesting mix of
      pragmatist language regarding the human and structuralist approaches to
      knowledge, resulting in professional identity problems still experienced today.
      However, recent developments offer an opportunity for occupational therapists to
      correct old identity problems through critically evaluating incompatible
      assumptions and carefully reading the prevailing cultural ethos.

PMID- 11833401
TI  - Interrater reliability, concurrent validity, responsiveness, and predictive
      validity of the Melville-Nelson Self-Care Assessment.
AB  - OBJECTIVE: This study examines psychometric characteristics of the Melville
      Nelson Self-Care Assessment (SCA), which is designed for occupational therapists
      working in skilled nursing facilities (SNFs) and subacute rehabilitation. Like
      the federally mandated Minimum Data Set, the SCA assesses seven self-care
      occupations in two ways: self-performance and support needed. METHOD:
      Participants were SNF patients receiving subacute rehabilitation. Primary and
      secondary diagnoses varied widely; mean age was 76.5 years (SD = 9.8). Using the
      SCA, the Functional Independence Measure (FIM), and the Klein-Bell Activities of
      Daily Living Scale, four teams of raters independently and simultaneously
      assessed 54 women and 14 men at admission and discharge; 40 participants were
      available for reassessment in their homes after discharge. RESULTS: Total self
      performance scores on the SCA showed (a) interrater reliability (mean ICC = .94);
      (b) concurrent validity with relevant areas of the FIM (rho = -.85) and the Klein
      Bell (rho = -.86); (c) responsiveness in detecting change from admission to
      discharge, t(67) = 6.3, p < .001, with a large effect size of 1.10; and (d)
      moderate predictive validity of caregiving time in the home (rho = -.44) and
      overall function in the home as measured by the total FIM (rho = -.55) and total
      Klein-Bell (rho = -.54) scores. The self-performance and support measures for the
      seven self-care areas all had acceptable interrater reliability and concurrent
      validity. Eating, personal hygiene, and bathing showed little or no
      responsiveness to change from admission to discharge, whereas positive change was
      substantial in bed mobility, transfers, dressing, and toileting. CONCLUSION: This
      instrument is recommended for use as part of a comprehensive occupational therapy
      model of practice in SNFs and subacute rehabilitation.

PMID- 11833403
TI  - Confluence: moving forward with affective strength.
AB  - The term confluent education describes a flowing together of the affective and
      cognitive elements of learning. Confluent education accords high value to affect
      because of its core principle that the realization of human potential includes
      attention to the affective elements of human nature. This article reviews the
      literature on confluent education, extends a previous introduction of the topic,
      and proposes an integration of affect into all realms of occupational therapy
      practice. The visual metaphors, philosophical principles, and practical
      strategies developed in the literature on confluent education are useful when
      applied to the functions of occupational therapy practitioners engaged in direct
      care, education, or research. Because the contexts within which occupational
      therapy practice occurs today often challenge its affective elements, the author
      proposes confluence as a timely approach. To advance into the future with the
      affective strength that has characterized occupational therapy since its
      inception is a matter of reclaiming the profession's heart.

PMID- 11833402
TI  - Development of a standardized instrument to assess computer task performance.
AB  - OBJECTIVE: The purpose of this study was to determine the psychometric properties
      of the Assessment of Computer Task Performance, specifically, the test-retest
      reliability, internal consistency, construct validity, and ability to
      discriminate between known groups. METHOD: This assessment comprises 14
      standardized and timed tasks. It was administered to 24 persons with upper
      extremity impairments and 30 with no impairments by a trained occupational
      therapist. To assess the test-retest reliability, participants in the impaired
      group were retested within 2 to 7 days. Intraclass correlation coefficients were
      calculated to determine test-retest reliability. Internal consistency was
      assessed with Cronbach's alpha, and factor analysis was conducted to examine
      construct validity. The Mann Whitney U Test was used to assess the test's ability
      to discriminate between the groups. RESULTS: Results indicated that the tool has
      excellent reliability and internal consistency, can discriminate between groups,
      and has appropriate construct validity. CONCLUSION: The Assessment of Computer
      Task Performance provides occupational therapists with an accurate test to
      measure computer performance and can assist them in providing computer access
      services.

PMID- 11833404
TI  - The relationship between hand strength and the forces used to access containers
      by well elderly persons.
AB  - OBJECTIVE: This study extended previous work of Rice, Leonard, and Carter [AJOT,
      52(8), 621-626] and examined the relationship between grip and pinch strengths
      and the forces produced while accessing common household containers in healthy,
      elderly persons. METHOD: Forty-two women and 9 men 60 years of age and older were
      assigned randomly to one of four order groups in a counterbalanced, repeated
      measures design. Grip strength was measured via a dynamometer and pinch strength
      via a pinch meter. The forces required to access six common household containers
      were measured with force sensing resistors applied to each container. Data
      analysis included Pearson product-moment correlations between the dependent
      variables of grip and pinch strength and force produced on the containers.
      Analyses of variance were used to determine differences by gender on the
      dependent measures and order of presentation of containers. RESULTS: A fair
      relationship (r = .31 to .44) was found between grip and pinch strength and the
      ability to open three containers. Little or no relationship was found between
      grip and pinch strength and the ability to open the remaining three containers (r
      = -.03 to .25). Significant gender differences existed on overall strength and
      the force used to access two of the six containers. No order effects were found.
      CONCLUSIONS: Strong relationships did not exist between the grip and pinch
      strength and the amount of force the elderly participants used to open the
      containers, which is similar to what Rice et al. found for younger persons. The
      participants appeared to use a greater proportion of their available strength
      when accessing the containers than did their younger counterparts previously
      studied. Further research is needed to determine at what level of weakness one
      would expect to see performance deficits in common daily occupations.

PMID- 11833405
TI  - Powered mobility and preschoolers with complex developmental delays.
AB  - OBJECTIVE: The purpose of this study was to explore the effects of a powered
      mobility riding toy on the participation behaviors of young children with complex
      developmental delays. METHOD: A single-subject withdrawal design was used to
      study the effects of powered mobility on child-initiated movement occurrences,
      initiation of contact with others, and affect. The participants were two young
      children with complex developmental delays, including spastic quadriplegia. The
      intervention consisted of having the children use a powered mobility riding toy
      in their school settings during gym class and outdoor recess. RESULTS: Primary
      findings were that use of the powered mobility riding toy (a) increased the
      number of self-initiated movement occurrences; (b) appeared to have some effect
      on initiation of contacts with adults and, for one child, negative adult
      initiations and positive peer initiations; and (c) did not have a clear impact on
      the amount of positive affect. CONCLUSION: For some young children with severe
      motor impairments and developmental delay, use of a powered mobility device may
      increase self-initiated movement occurrences during free play.

PMID- 11833407
TI  - Private benefit, joint ventures, and the death of healthcare as an exempt
      purpose.
AB  - The private benefit doctrine has become the IRS' main policing tool for tax
      exemption in healthcare. The IRS' modern interpretation of private benefit has
      clearly become the major limitation on exempt status. This Article begins by
      tracing the common law origins of this doctrine and how it became such an
      integral part of the IRS' analysis. Next, the author looks at policy issues
      regarding alternative analysis to the private benefit doctrine in cases of joint
      ventures between healthcare providers and for-profit investors. Finally,
      Professor Colombo questions the expanded use of this doctrine, arguing that in
      its current form it has no sound legal or policy under-pinnings.

PMID- 11833406
TI  - Sensory processing issues associated with Asperger syndrome: a preliminary
      investigation.
AB  - OBJECTIVE: The purpose of this study was to identify the sensory processing
      patterns of children with Asperger syndrome. METHOD: Researchers compared the
      performance of 42 children with Asperger syndrome and 42 children without
      disabilities on section and factor scores of the Sensory Profile. RESULTS: As
      reported by parents on the Sensory Profile, the children with Asperger syndrome
      were significantly different from children without disabilities on 22 of 23
      items. This result was obtained with good power estimates (.997-1.00) and large
      effect sizes (02 = .267-.732). Both groups of children performed the same on
      modulation of visual input affecting emotional responses and activity level.
      CONCLUSION: This study provides initial evidence that clear differences exist in
      the sensory processing patterns of children with Asperger syndrome when compared
      with peers without disabilities.

PMID- 11833408
TI  - One for you and two for me: revenue sharing arrangements in charitable healthcare
      organizations.
AB  - Charitable healthcare organizations have often borrowed from the methods of their
      for-profit counterparts in compensating physicians and other business partners.
      This is done in order to provide needed services to their communities, and to
      protect their charitable assets by sharing risk and preserving limited capital.
      One of the most controversial compensation methods in use by such organizations
      is the revenue sharing arrangement. In use for over thirty years, these
      arrangements have received close scrutiny and inconsistent treatment by the
      Internal Revenue Service (IRS) and have been the subject of critics' ire as an
      impermissible transgression of the fundamental line between charities and
      commercial enterprises. The author, however, concludes that revenue sharing
      arrangements serve an important purpose in enabling charitable healthcare
      organizations to fulfill their missions, that the IRS and the Treasury have now
      made clear that there is not a higher standard governing their use, and that
      these arrangements are consistent with charitable operation when an appropriate
      process and safeguards are in place to prevent payment of unreasonable
      compensation.

PMID- 11833409
TI  - TBOR2 compliance plans: from rebuttable presumption to enforcement.
AB  - This Article analyzes the implications and strategies of incorporating the
      Taxpayer Bill of Rights 2 ("TBOR2") into tax-exempt healthcare organizations'
      compliance plans. Beginning with a brief overview of TBOR2, the author examines
      the presumption of fair market value, how such organizations establish safe
      harbors, the current Internal Revenue Service (IRS or Service) position regarding
      enforcement of TBOR2, and the lurking potential for "whistleblowers" to start
      auditory procedures with an eye toward IRS bounties. Mr. Griffith concludes that
      the best advice for exempt organizations is to follow the rebuttable presumption
      procedure for all transactions involving potential disqualified persons,
      including staff and employed physicians, and seek to fit within the safe harbors
      for the less routine and larger of those transactions.

PMID- 11833410
TI  - A contemporary reexamination of revenue ruling 69-545 and the promotion of health
      rationale for exemption.
AB  - In recent years, Revenue Ruling 69-545 has generated considerable discussion
      about what is necessary to satisfy the "promotion of health" standard of
      charitable exemption under Section 501(c)(3). This Article reviews the
      development of the standards of exemption applicable to nonprofit hospitals,
      including Revenue Ruling 56-185 and Revenue Ruling 83-157. It then provides a
      detailed discussion of Revenue Ruling 69-545 and sets forth the author's view on
      how the Ruling's factual elements should be interpreted. The author concludes
      that the promotion of health rationale should not be limited by treating the fact
      patterns of Revenue Ruling 69-545 as prescriptive of a multifaceted test of
      exemption, or by seeking to impose a mandatory charity care requirement as a
      precondition of exemption. Rather, a flexible approach to promotion of health
      should be embraced by the Internal Revenue Service (IRS), practitioners, and the
      courts.

PMID- 11833412
TI  - Healthcare compliance table of acronyms.

PMID- 11833411
TI  - Antitrust issues in the settlement of pharmaceutical patent disputes, Part II.
AB  - The settlement of patent disputes in the pharmaceutical industry, and the
      possible antitrust issues arising therefrom, are of notable concern to the
      Federal Trade Commission. In this Comment, based on his second speech on the
      subject, Commissioner Leary re-examines some of this earlier positions under the
      light of the Commission's further experience with these matters, and provides the
      industry with some additional objective standards under which it may legally
      operate. With the Hatch-Waxman Act as a backdrop for patent settlements between
      manufacturers of patented drugs and potential generic entrants to the market, the
      Commissioner reviews a variety of scenarios that may or may not be permissible.
      After initially noting the circumstances of presumptively valid settlements,
      Commissioner Leary reviews the often complex settlement structures that will be
      deemed unlawful when and if the finding of reverse payments is evidenced.
      Finally, the Commissioner concludes with a brief examination of other settlement
      structures and offers his general views as to their likely legality.

PMID- 11833413
TI  - [Identification of the existence of luteinizing hormone in pituitary vacuoles of
      rats].
AB  - It is generally believed that glycoprotein hormone exists in granules of the
      gonadotrophin (GTH) cells, and recent studies on the formation and secretion of
      glycoprotein hormones also concern much on the changes in the pituitary granules.
      In our previous studies, it was found that the secretion of luteinizing hormone
      (LH) was closely related to the morphological changes in pituitary vacuoles of
      rats, and the morphology of GTH cells was also closely related to the changes in
      vacuolar morphology. Therefore, it appears that there exists an inseparable
      relationship between the storage and secretion of LH and pituitary vacuoles. In
      order to examine whether the pituitary vacuoles contain LH in rats, and to
      further explore if LH is stored and released by the pituitary vacuoles, the
      vacuoles were separated and purified from pituitary, cortex and liver tissues by
      density gradient centrifugation. The vacuolar protein components, LH and
      glycoproteins were determined by the methods of SDS-PAGE, Western immunoblot and
      Con A/HRP, respectively. The results showed that (1) abundant protein components
      with various molecular masses were present in the vacuoles of the pituitary,
      cortex and liver in male, female and ovariectomized rats, and some of the protein
      components were similar in the molecular mass; (2) both pituitary tissues and
      vacuoles contained LH, and their LH levels had no significant difference by
      quantitative analysis of extracted protein samples; and (3) glycoproteins of
      various molecular masses were found in the vacuoles of the pituitary, cortex and
      liver, but the same position of stained glycoprotein band and LH molecular mass
      was only observed in the pituitary vacuoles. From the results given above, it can
      be concluded that LH specifically exists in the pituitary vacuoles, although
      there are some similar protein components in various cellular vacuoles. The
      possibility was further demonstrated at the molecular level that the pituitary
      vacuoles may have the function of storing and releasing LH due to the pituitary
      vacuoles containing LH with assembled glycone.

PMID- 11833414
TI  - [Relationship between dopamine and iron contents in the brain of parkinsonian
      rats].
AB  - Using fast cyclic voltammetry (FCV), atomic absorption/flame emission
      spectrophotometry and high performance liquid chromatography for electrochemical
      detection, we studied the change in iron content in the substantia nigra (SN) of
      6-hydroxydopamine (6-OHDA) lesioned Parkinsonian (PD) rats and the toxic effect
      of intranigral injection of iron on DA neurons. The neuroprotective effect of
      desferrioxamine mesylate was also observed. The results are as follows. (1) The
      iron content in SN on the lesioned side of 6-OHDA-lesioned PD rats was about
      three times as high as that in nonstandard PD rats. (2) The iron content in
      caudate putamen (CPu) on the lesioned side of PD rats was not different from that
      on the unlesioned side. (3) DA release as well as the content of DA and its
      metabolites were significantly decreased on the lesioned side of PD rats. (4) In
      the rats pretreated with intracerebroventricular desferrioxamine mesylate before
      6-OHDA injection, the release and content of DA on the lesioned side were not
      significantly different from those on the unlesioned side. (5) Intranigral
      injection of 40 micrograms FeCl3 resulted in a dramatic reduction of both DA
      release and content in CPu. The above results strongly suggest that 6-OHDA
      reduces the DA release from CPu, in which iron plays an important role. Elevation
      of iron content in SN is one of the mechanisms responsible for the reduction of
      DA content. Desferrioxamine mesylate may exert a protective action on
      dopaminergic neurons.

PMID- 11833415
TI  - [Effects of Bay K8644 and nifedipine on L-type Ca2+ channels in hypothalamic
      neurons of rats].
AB  - To investigate the effects of Bay K8644 and nifedipine on L-type of Ca2+ channels
      in hypothalamic neurons, the cell-attached patch-clamp technique was used to
      record Ca2+ current from isolated neurons. The results showed that the averaged
      open time and NPo were markedly increased by Bay K8644, but had no effect on
      channel conductance. Nifedipine, on the contrary, had an inhibitory effect on the
      L-type Ca2+ channels.

PMID- 11833416
TI  - [Properties of KATP channels in hippocampal CA1 pyramidal neurons from adult
      rats].
AB  - Properties of KATP channels in acutely dissociated hippocampal CA1 pyramidal
      neurons of adult rats were studied with inside-out patch-clamp technique. With
      symmetrical 140 mmol/L K+ on both sides of the excised membrane, the single
      channel conductance was approximately 63 pS and the reversal potential was 1.71
      mV. These channels had a weak inward rectifying property. Channels' openings
      interrupted by shorter closed intervals were more frequently observed at negative
      holding potential than at positive holding potential. However, noticeable voltage
      dependence was not found in channel open probability. ATP applied at the
      cytosolic side inhibited channel activity in a concentration-dependent manner
      with an IC50 of 0.1 mmol/L. Sulphonyluren tolbutamide (1 mmol/L), a specific KATP
      channel blocker, added to the bath completely suppressed the channel activity,
      while diazoxide (1 mmol/L), a KATP channel opener, had no apparent effect.

PMID- 11833417
TI  - [5-HT3 receptors in amygdala mediate neuroimmunomodulation in rats].
AB  - The present study was to explore the possible immunomodulatory role of 5-HT3
      receptors in the amygdala in rats. Concanovalin A (Con A)- and lipopolysaccharide
      (LPS)-stimulated splenocyte proliferation response (SPR), production of IL-2,
      activity of natural killer (NK) cells and serum cortisol were measured by 3H-TdR
      incorporating method, MTT method and RIA, respectively. The Con A- and LPS
      stimulated SPR was enhanced in a dose-dependent manner by 5-HT3 receptor
      antagonist granisetron (GNT) (0.1-0.4 mg/kg, i.p.). SPR was also enhanced by
      intracerebroventricular (icv) administration of 1-phenylbiguanide (PBG, 10
      micrograms/d). Con A-stimulated SPR and production of IL-2 were increased either
      by bilateral or by unilateral central amygdala (CeA) microinfusion of PBG (0.5
      microgram/side), but LPS-induced SPR and NK cell activity were not affected. On
      the contrary, the LPS-induced SPR was increased by either bilateral or unilateral
      basomedial amygdala (BmA) microinfusion of PBG (0.5 microgram/side). The plasma
      cortisol level was significantly raised by CeA or BmA PBG microinfusion, but the
      effect induced by PBG intra-CeA was greater than that induced by PBG intra-BmA (P
      < 0.01). The effects of icv PBG and intra-amygdala infusion were antagonized by
      granisetron. Asymmetrical modulation of immune reactivity by 5-HT3 receptors in
      CeA or BmA was not observed in these experiments. It is suggested that 5-HT3
      receptors within the amygdala may modulate rat mitogen-stimulated SPR in
      different manners.

PMID- 11833418
TI  - Hemodynamic effects of agmatine in Dahl salt-sensitive hypertensive and Dahl salt
      resistant rats.
AB  - The hemodynamic effects of agmatine were investigated in anaesthetized Dahl salt
      sensitive (DS) hypertensive and Dahl salt-resistant (DR) rats. The results are as
      follows. (1) Agmatine (1, 10, 20 mg/kg i.v.) decreased heart rate (HR), mean
      arterial pressure (MAP), left ventricular blood pressure (LVP), the first
      derivative of LVP (LV dp/dt), cardiac index (CI) and total peripheral resistance
      index (TPRI) in a dose-dependent manner in both DS and DR rats, and the decreases
      in MAP, LVP, +/- LV dp/dtmax and TPRI at the same dose of agmatine in DR rats
      were less than those in DS hypertensive rats. Specifically, agmatine at high dose
      (20 mg/kg) induced a delayed increment of hemodynamic parameters in DS
      hypertensive rats, but not in DR rats. (2) Idazoxan (2.5 mg/kg), an antagonist
      for I2 over I1-imidazoline receptors and alpha 2-adrenoceptor receptors (alpha 2
      AR), only partially blocked the effects of agmatine (10 mg/kg). (3) Yohimbine (4
      mg/kg), a selective alpha 2-AR antagonist, also partially attenuated the effects
      of agmatine. (4) Efaroxan (2.5 mg/kg), a selective antagonist for I1 over I2
      imidazoline receptors and alpha 2-AR, could completely block the effects of
      agmatine. Taken together, the results indicate that agmatine can dose-dependently
      decrease HR, MAP, LVP, +/- LV dp/dtmax, CI and TPRI in DS hypertensive and DR
      normotensive rats. The hemodynamic effects of agmatine are mediated mainly by I1
      IR with the participation of I2-IR and alpha 2-AR.

PMID- 11833420
TI  - [Ameliorative effects of adrenomedullin on rat cardiac sarcoplasmic reticulum
      injured by isoproterenol].
AB  - Five indices were used to assess the degree of the ameliorative effects of
      adrenomedullin (Adm) in isoproterenol (ISO) induced injury of cardiac
      sarcoplasmic reticulum (SR) of rats: +/- LV dp/dtmax, SR Ca2+ uptake, Ca2+
      release (in nmol/mg SR protein) and Ca(2+)-ATPase activity. Adm (5 x 10(-5)
      mol/L) was perfused into rat heart before cardiac function +/- LV dp/dtmax was
      determined. Cardiac SR was purified and SR Ca2+ uptake, Ca2+ release, Ca(2+)
      ATPase activity, and 3H-ryanodine maximal binding (Bmax) were measured. After
      perfusion of Adm (5 x 10(-5) mol/L), the +LV dp/dtmax and -LV dp/dtmax in ISO
      injured heart were increased by 16.9% (2,135 +/- 281 vs 1980 +/- 302, P < 0.05)
      and 29.2% (1375 +/- 267 vs 1064 +/- 355, P < 0.05), respectively. Cardiac SR Ca2+
      uptake and Ca2+ release were increased by 23.0% (15.0 +/- 1.4 vs 12.2 +/- 1.2, P
      < 0.01) and 43.5% (6.6 +/- 1.0 vs 4.6 +/- 0.6, P < 0.01), respectively. Ca(2+)
      ATPase activity and 3H-ryanodine binding were increased by 23.0% (P < 0.01) and
      42.2% (P < 0.05), respectively. It seems that Adm exerted a protective effect on
      cardiac function in injured rat heart by enhancing SR Ca2+ uptake and release,
      suggesting that Adm may play a therapeutic role in myocardial injury.

PMID- 11833419
TI  - [Inhibition of PKC and ERK1/2 in cultured rat vascular smooth muscle cells by
      angiotensin-(1-7)].
AB  - The present study was undertaken to investigate the effects of angiotensin-(1
      7)[Ang-(1-7)] on the proliferation and expression of protein kinase C (PKC) and
      extracellular regulated protein kinases (ERK1/2) of vascular smooth muscle cells
      (VSMCs) by techniques of Western blot, 3H-thymidine (3H-TdR) and 3H-leucine (3H
      Leu) incorporation. Ang II increased VSMC DNA and protein synthesis, and promoted
      protein expression of PKC-zeta and ERK1/2. In contrast, Ang-(1-7) not only
      inhibited PKC-zeta and ERK1/2 protein content, but also decreased Ang II mediated
      VSMC hyperplasia, as compared with the controls (P < 0.01 or P < 0.05). These
      results suggest that Ang-(1-7) may inhibit VSMC proliferation by influencing
      protein expression of PKC-zeta and ERK1/2.

PMID- 11833421
TI  - Renal ischemia enhances electrical activity and Fos protein expression of the
      rostral ventrolateral medullary neurons in rats.
AB  - The effects of renal ischemia on spontaneous electrical activity and Fos protein
      expression of nucleus paragigantocellularis lateralis (PGL) in rostral
      ventrolateral medulla (RVLM) were observed in 67 anesthetized Sprague-Dawley rats
      with sinoaortic denervation by using extracellular recording and
      immunohistochemical techniques. The results obtained are as follows. (1) Renal
      ischemia increased the discharge rate from 11.40 +/- 1.08 to 21.1 +/- 1.74
      spikes/s (P < 0.001) in 28 out of 30 PGL neurons, while blood pressure and heart
      rate had no significant change (P > 0.05). (2) Administration of 8
      phenyltheophylline (8-PT), an adenosine receptor antagonist, did not affect the
      discharge rate of PGL neurons, but could partially inhibit the effects of renal
      ischemia in 17 units (P < 0.05). (3) Renal ischemia resulted in a remarkable
      increase in the number of Fos-like protein immunoreactive PGL neurons in the RVLM
      (P < 0.01). (4) Fos protein expression induced by renal ischemia was
      significantly inhibited by pretreatment with 8-PT (P < 0.05). Taken together, it
      is concluded that renal ischemia induces an increase in spontaneous electrical
      activity and Fos protein expression in PGL neurons of RVLM, and that adenosine
      released within ischemic kidney may be involved in such effects.

PMID- 11833422
TI  - [Changes in aldosterone binding activity of kidney cytosol after stress in rats
      and the regulation].
AB  - To observe the changes in aldosterone binding activity of kidney cytosols after
      pathological stress in rats and the regulation, binding capacity (Rt) and
      apparent dissociation constant (Kd) of aldosterone binding activity of kidney
      cytosols in normal, low-degree or heavy-degree scalded rats were measured by
      radioligand binding assay using [3H]aldosterone as the ligand. Changes in Rt and
      Kd of aldosterone binding activity were observed after injection of anti-rat TNF
      alpha and IL-1 beta antibodies, alpha-melanocyte-stimulating hormone (alpha-MSH)
      and KPV peptide (Ac-D-Lys-L-Pro-D-Val). The results indicated that there were two
      types of aldosterone binding activities in kidney cytosol with different Rt and
      Kd, and the Rt of heavy-degree scalded rats (Rt1: 22.4 +/- 5.4 fmol/mg pro, Rt2:
      196.3 +/- 32.5 fmol/mg pro) was lower than that of the control group (Rt1: 41.6
      +/- 7.2 fmol/mg pro, Rt2: 317.6 +/- 70.0 fmol/mg pro) (P < 0.01; P < 0.01); while
      the Rt of low-degree scalded rats (Rt1: 41.4 +/- 5.0 fmol/mg pro, Rt2: 314.8 +/-
      45.7 fmol/mg pro) was not significantly different from that of the control group
      (P > 0.05; P > 0.05). Injection of anti-rat TNF alpha and IL-1 beta antibodies,
      alpha-MSH and KPV prevented Rt of aldosterone binding activity from decrease in
      kidney cytosol of rats with heavy-degree scald. These findings suggest that
      aldosterone binding activity may be down-regulated in heavy-degree scalded rats,
      but it may be reversed by injection of anti-rat TNF alpha and IL-1 beta
      antibodies, alpha-MSH and KPV.

PMID- 11833423
TI  - [Down-regulation of ETA receptor of vascular smooth muscle cells by 17 beta
      estradiol].
AB  - In the present study, the effects of 17 beta-estradiol on vascular reactivity of
      ovariectomized rats and proliferation of cultured rat aortic smooth muscle cells
      were studied. The vascular reactivity was significantly increased in
      ovariectomized rats compared with the sham-operated animals. The selective ETA
      receptor antagonist BQ123 inhibited the increase in [3H]-TdR incorporation in
      response to ET-1 on vascular smooth muscle cells (VSMCs). 17 beta-estradiol also
      attenuated the ET-1 effects in a dose-dependent manner. The results of RT-PCR and
      Western blot show that expression of ETA receptor was decreased after treatment
      with 17 beta-estradiol. The effect of 17 beta-estradiol was partially inhibited
      by estrogen receptor antagonist tamoxifen. The above results demonstrate that
      proliferation of VSMCs stimulated by ET-1 was mainly mediated through ETA
      receptor. Due to the down-regulation of ETA receptor and mediation of estrogen
      receptor, 17 beta-estradiol inhibits the ET-1-induced proliferation of VSMCs and
      decreases the vascular reactivity of ovariectomized rats.

PMID- 11833424
TI  - [Angiotensin II in rostral ventrolateral medulla mediates amino acids release
      from spinally projecting nerve terminals in the spinal cord].
AB  - Microdialysis in the intermediolateral column (IML) was employed to examine amino
      acids release induced by angiotensin II (ANG II) applied into the rostral
      ventrolateral medulla (RVLM). Microinjection of ANG II (100 pmol, n = 11) into
      the RVLM significantly increased (P < 0.01) the release of aspartate (from 4.75
      +/- 1.01 to 8.90 +/- 2.28 pmol/20 microliters) and glutamate (from 18.99 +/- 8.64
      to 73.88 +/- 29.26 pmol/20 microliters) in the spinal cord. The increase of
      glutamate release was significantly attenuated (P < 0.05) by pretreatment with
      losartan (10 nmol, n = 8) at the same RVLM site. Immunofluorescence double
      labeling combined with confocal microscopic observation demonstrated that 62%-91%
      of the glutamatergic neurons in the RVLM were double-labeled with AT1 receptors,
      supporting the view that ANG II-induced glutamate release in the spinal cord may
      arise from the AT1 receptor-containing glutamatergic spinally projecting neurons
      in the RVLM.

PMID- 11833425
TI  - [Projections of 5-HTergic fibers to the spinal phrenic nucleus and medullary
      phrenic premotor neurons in the cat].
AB  - Experiments were performed on 6 adult cats. Brainstem neurons that project to the
      phrenic nucleus were retrogradely labeled by microinjection of WGA-HRP into the
      spinal phrenic nucleus. The brainstem sections were double processed for HRP
      histochemical staining with TMB-DAB method and 5-HT immunohistochemical staining
      with anti-5-HT primary antibody and FITC conjugated immunofluorescent secondary
      antibody. HRP-5-HT double-labeled neurons were observed mainly in the nucleus
      raphe pallidus. A few double-labeled neurons were also observed in nucleus raphe
      obscurus and nucleus raphe magnus. 5-HT immunopositive terminal fibers were
      observed in the vicinity of HRP single-labeled neurons (phrenic premotor neurons)
      located in the nucleus ambiguus and ventrolateral solitary tract nucleus. The
      results indicate that the 5-HTergic neurons in the nucleus raphe pallidus send
      axonal projections to the phrenic nucleus, and that the brainstem phrenic
      premotor neurons also receive 5-HTergic axonal projections.

PMID- 11833426
TI  - Desensitization of adrenomedullin and calcitonin gene-related peptide receptors
      in vascular smooth muscle cells--effects of receptor activity-modifying protein.
AB  - Recent researches suggest that adrenomedullin (ADM) and calcitonin gene-related
      peptide (CGRP) bind to the same calcitonin receptor-like receptors (CRLR), with
      receptor specificity being determined by a receptor activity-modifying protein
      (RAMP). Our objective was to explore the significance of CRLR/RAMP hypothesis in
      cardiovascular tissues through experiments on the phenomenon of desensitization
      of both ADM and CGRP receptors using cultured rat aortic vascular smooth muscle
      cells (VSMCs). VSMCs were incubated for 20 min either in serum-free medium (SFM)
      alone or in the SFM containing vasoactive agonist [10(-8) mol/L ADM, CGRP and
      proadrenomedullin (PAMP)]. Cells were washed twice and incubated for another 20
      min in SFM containing a repetitive agonist ADM or CGRP and 0.5 mmol/L isobutyryl
      methylxant (an inhibitor of phosphodiesterase). VSMCs were harvested and assayed
      for cAMP. Exposure of VSMCs to ADM, CGRP, or PAMP alone increased intracellular
      cAMP generation by 191% (P < 0.01), 385% (P < 0.01) and 67% (P < 0.05),
      respectively, compared with SFM group. Pre-treatment of VSMCs to ADM or CGRP
      decreased cAMP generation in response to subsequent stimulation with CGRP by 44%
      (P < 0.05) and 48% (P < 0.01), respectively. Pre-treatment of VSMCs with 100
      nmol/L H-89, a protein kinase A (PKA) inhibitor, abolished the desensitization of
      CGRP-acting receptor, implying that this desensitization was mediated through
      PKA. In contrast, there was no attenuation in cAMP response to stimulation with
      ADM by pre-exposure to ADM or CGRP. Identical results were seen with or without
      PKA inhibition by H-89. Pre-exposure of VSMCs to PAMP resulted in no change in
      cAMP generation in response to subsequent stimulation with ADM or CGRP. These
      results indicate that ADM receptors do not desensitize in VSMCs in contrast to
      CGRP-receptors, which are desensitized by pre-exposure to ADM or CGRP. These data
      also suggest that the desensitization phenomenon of ADM is different from that of
      CGRP.

PMID- 11833427
TI  - Afferent projection to the retrotrapezoid nucleus from respiratory related
      structures in the brainstem of rabbit--a retrograde CB-HRP tracing study.
AB  - Experiments were performed on 10 adult rabbits. After microinjection of cholera
      toxin B-subunit conjugated horseradish peroxidase (CB-HRP) into the
      retrotrapezoid nucleus (RTN), retrogradely labeled neurons were mainly observed
      in the Kolliker-Fuse nucleus (KF), the medial parabrachial nucleus (PBM) and the
      lateral parabrachial nucleus (PBL). A few labeled neurons were also observed in
      the ventrolateral solitary tract nucleus, the ambiguus and retroambiguus nuclei,
      and the ventromedial area of retrofacial nucleus. Labeled terminal fibers were
      mainly observed in the retrofacial nucleus, the ambiguus and retroambiguus
      nuclei, the ventrolateral area of solitary tract nucleus, and the PBL-PBM-KF. The
      above results show that the RTN has axonal connections with the pontine and
      medullary respiratory related structures.

PMID- 11833428
TI  - [Blind patch clamp whole-cell recording technique for neurons in hippocampal
      slices].
AB  - The blind patch clamp whole-cell recording technique for CA1 pyramidal neurons in
      hippocampal slices was carefully introduced, the key procedures and the points
      for attention were emphasized. Using the "blind" method, we analyzed the
      properties of synaptic activity, the current features of Ca2+ channels and
      glutamate, GABA receptors. Our results provide a scientific basis for study of
      dynamic properties of ion channels on hippocampal neurons and the effects of
      drugs on synaptic activity by using the blind whole-cell recording technique.

PMID- 11833429
TI  - A comparison of oral health in elderly populations seeking and not seeking dental
      care.
AB  - The General Oral Health Assessment Index (GOHAI) has been recommended for use as
      an outcome measure in the evaluation of dental treatment. This study was designed
      to assess the ability of the GOHAI in the evaluation of differences in those
      actively seeking dental care compared with those not seeking care. GOHAI was self
      administered to two samples of elderly individuals, over 65 years of age, in the
      Columbus, OH, area. The first sample was ambulatory individuals living in a
      nursing home in Columbus, and the second sample consisted of patients accessing
      dental care at The Ohio State University (OSU) dental school clinics. Other
      variables used in this study were age, gender, self-rated oral and general
      health, and use of prostheses. Overall mean GOHAI score in the nursing home
      respondents was significantly higher (32.1 +/- 3.0) when compared with that of
      dental patients (mean, 30.4 +/- 3.9, p = 0.01). Mean GOHAI scores for all
      categories of variables used were consistently higher (better) in the nursing
      home respondents than for the dental patients. Results of this study show that
      self-assessed oral health measured by the GOHAI was higher for those individuals
      not seeking dental care than for those actively seeking dental care. The GOHAI is
      sensitive as an outcome measure in differentiating between individuals actively
      seeking care and those not seeking care.

PMID- 11833430
TI  - Periodontal status and treatment needs among Spanish hospitalized psychiatric
      patients.
AB  - The purpose of this study was to evaluate the periodontal status and treatment
      needs (by CPITN) of 565 patients hospitalized in a psychiatric facility in
      Seville, Spain. The results of this study showed that 31.7% of the patients were
      edentulous and that 68.3%% were dentate. Of the dentate subjects, 8.5% were found
      to have a healthy periodontium, 14.2% had bleeding on probing, 43.8% had
      calculus, 24.6% had shallow pockets, and 8.9% had deep pockets. The results of
      the study also showed that the severity of periodontal disease increased
      significantly with age and the length of time of hospitalization. The need for
      oral hygiene instruction among the dentate population was determined to be 91.5%,
      and the need for treatment (oral prophylaxis and scaling) was 77.3%. These
      findings suggest that hospitalized psychiatric patients in Spain are in dire need
      of preventive dentistry.

PMID- 11833431
TI  - A study of the effectiveness of oral midazolam as a dental pre-operative sedative
      and hypnotic.
AB  - Orally administered Midazolam at dosages of 0.5, 0.6, and 0.75 mg/kg was used
      with 34 healthy, uncooperative pediatric dental patients. Effective pre-operative
      sedation occurred within approximately 15 minutes with a 30- to 40-minute
      duration of action. Blood pressure and respiration remained stable throughout.
      The numbers and types of procedures performed were dependent on the degree of
      sedation, the behavior of the patient, the experience of the operator, and the
      operator's ability to administer the medication. The ideal dosage appears to be
      0.6 mg/kg, with an average change of 1.43 Frankel Units in behavior modification.
      A dosage of 0.5 mg/kg appears to yield erratic results, while a dosage of 0.75
      mg/kg offers little advantage with greater potential for adverse reactions. The
      oral administration of Midazolam for pediatric patients with extreme behavioral
      problems, such as Attention Deficit Hyperactive Disorder, was of little advantage
      and may produce an idiosyncratic reaction. Midazolam's quick onset and short
      duration of action, coupled with its ideal properties of sedation, relaxation,
      and amnesia, offer a viable alternative for treating the anxious, uncooperative
      pediatric dental patient.

PMID- 11833432
TI  - Necrotizing fasciitis of the head and neck: review of the literature and report
      of a case.
AB  - Necrotizing fasciitis is a rapidly spreading, life-threatening, bacterial
      disease. Mortality rates have been estimated to vary between 8.7% and 74%.
      Mortality depends on many factors, one of which is early recognition. Necrotizing
      fasciitis of dental origin has a low prevalence and as such presents diagnostic
      challenges for the dentist. The literature is reviewed, and a case history is
      presented.

PMID- 11833433
TI  - Using intravenous sedation to manage adults with neurological impairment.
AB  - Dental care for most medically compromised patients can be accomplished if
      dentists understand the patients' specific medical conditions and use standard
      conservative behavioral or physical modifications to prevent complications from
      occurring. However, in patients who have certain types of neurological
      conditions, specifically Alzheimer's disease and other types of dementia, dental
      management typically presents a greater challenge, because, in most kinds of
      dementia, patients are unable to follow directions or cooperate with simple
      instructions such as opening their mouths or holding their heads still. This
      report describes a three-year retrospective chart review of patients, diagnosed
      with a neurologic impairment, who underwent intravenous sedation at the
      Department of Veterans' Affairs Medical Center in Lexington, Kentucky. The goals
      of this review were to investigate the average doses of commonly used sedative
      agents, review complications as a result of the sedation, and comment on the
      safety of intravenous sedation as a means to treat elderly adults with a
      neurological disability.

PMID- 11833434
TI  - Letter from the secretary.

PMID- 11833435
TI  - Who is responsible--dentist or anaesthetist?

PMID- 11833436
TI  - Katie Dougal. A legacy for improvement.

PMID- 11833437
TI  - Nasal and labial anaesthetic mask.

PMID- 11833438
TI  - Practising through the changes.

PMID- 11833440
TI  - Letter from the secretary.

PMID- 11833439
TI  - Who is responsible?

PMID- 11833441
TI  - Approaching the millennium safe and sound. SAAD annual conference and AGM. The
      Royal Society of Medicine. Saturday 9th October 1999.

PMID- 11833443
TI  - Hypnotherapy general anaesthesia and sedation. A case report.

PMID- 11833442
TI  - Letter from the secretary.

PMID- 11833444
TI  - Evidence-based practice: implications for social work in AIDS care.

PMID- 11833445
TI  - Cidofovir: progress in the treatment of progressive multifocal encephalopathy
      (PML)?

PMID- 11833446
TI  - Don't ask don't tell don't work when it comes to suicide and HIV.

PMID- 11833447
TI  - With HAART success, managing dental caries is again important.

PMID- 11833448
TI  - Nutrition. L-carnitine for the treatment of hypertriglyceridemia in HIV.

PMID- 11833449
TI  - Ryan White CARE Act to focus on HIV-infected incarcerated.

PMID- 11833450
TI  - New cholesterol guidelines emphasize risk assessment.

PMID- 11833451
TI  - Lipid-lowering therapy stabilizes plaque, reduces events by limiting
      inflammation.

PMID- 11833452
TI  - Review of clinical trial data reaffirms safety of statin therapy.

PMID- 11833453
TI  - Protective effects of HDL-C and need to raise low levels explored.

PMID- 11833454
TI  - Risk factors common to insulin resistance and atherosclerosis explain why
      diabetes is a cardiovascular disease.

PMID- 11833455
TI  - Heart protection study finds simvastatin reduces vascular risk in a wide range of
      high-risk patients.

PMID- 11833456
TI  - Cholesterol goals established for patients with diabetes and metabolic syndrome.

PMID- 11833457
TI  - Dyslipidemia of insulin resistance syndrome explained; need for treatment to
      reduce risk emphasized.

PMID- 11833458
TI  - [Cationization, a process for the delivery of antibodies to the central nervous
      system. Problems encountered in its application for immunotherapy strategies such
      as those for clostridial poisoning].
AB  - The central nervous system is separated from the rest of the body by the blood
      brain barrier. This barrier prevents many substances, such as the antibodies, to
      penetrate into the brain making it difficult to use them for the treatment of
      brain diseases, such as tetanus and botulism. These two diseases are caused by
      the development of bacilli of the genus Clostridium which release neurotropic
      toxins. Specific antibodies can neutralize toxin activity when the toxin is in
      the blood but are ineffective when it is transported into nerve cells. Various
      invasive strategies have been used to deliver antibodies to the brain. However,
      they can induce seizures and transient neurologic deficits and may be applicable
      only for diseases restricted to the brain surface. Physiologically based
      strategies utilizing transport systems naturally present at the blood-brain
      barrier appear to be a more promising approach to brain delivery of antibodies.
      Cationization is a chemical treatment that causes the conversion of superficial
      carboxyl groups on a protein into extended primary amino groups. This is used to
      increase interactions of this protein with the negative charges at the luminal
      plasma membrane of the brain endothelial cells. The cationized protein can then
      undergo adsorptive mediated transcytosis through the blood-brain barrier. There
      are many problems yet to be solved in successfully carrying out in vivo
      applications of cationized antibodies. One of these problems is that
      cationization can cause damage to an antibody molecule and, thus, can compromise
      its binding affinity. Depending on the radiolabelling of the cationized
      antibodies, a serum inhibition phenomenon can possibly alter the pharmacokinetics
      and the organ distribution of these molecules. The antibodies can be cationized
      using various, synthetic (hexamethylenediamine) or naturally occuring (e.g.,
      putrescine) polyamines. Hexamethylenediamine-induced and putrescine-induced brain
      uptakes of various antibodies and proteins have been shown, but the results
      obtained suggest that cationization with putrescine may be a more efficient
      approach to blood-brain barrier delivery. The development of animal or cellular
      models to check for therapeutic efficacy of cationized antibodies is necessary.
      In spite of the difficulties, the studies described in this paper indicate that
      cationization can be a realistic delivery strategy for carrying antibodies across
      the blood-brain barrier. The advances made in antibody technologies help generate
      more appropriate immunological structures for brain transfer with better effector
      functions and decreased immunogenicity or toxicity. Taken together, these two
      aspects can lead to further developments in treatment of intoxications caused by
      the clostridial neurotoxins.

PMID- 11833459
TI  - [Anchoring cytokines to cancer cells using diphtheria toxin: better than
      immunotherapy by gene transfer?].
AB  - Many cytokines are able to stimulate the antitumor immune response. However, in
      order to avoid the toxic effects due to systemic injection, it is necessary to
      concentrate the cytokines in the tumor microenvironment. Current methods, based
      on the transfer of cytokine genes into tumor cells, still suffer drawbacks. We
      describe an alternative approach using recombinant cytokines genetically
      conjugated to a membrane anchor derived from diphtheria toxin. Interleukin-2
      anchored to lymphoma and melanoma cells remained displayed on their surface and
      were not internalized. Injection of these cell preparations to mice led to an
      immune response able to prevent or slow tumor growth following tumor challenge.

PMID- 11833460
TI  - [Endosomes and toxin translocation].
AB  - In this review we discuss data obtained by our group regarding the entry of
      toxins, especially ricin, diphtheria toxin (DT) and Pseudomonas exotoxin A (PE)
      into animal cells. We studied the translocation process of these toxins using
      endosomes purified from lymphocytes. This process is rate-limiting for toxicity
      and enables these toxins to reach the cytosol where they will inactivate the
      protein synthesis system and kill the cell. We could show that each of these
      toxins uses a different strategy to cross the endosome membrane. Whereas ricin
      transmembrane transport only relies on cytosolic ATP hydrolysis, PE first
      requires exposure to the low endosomal pH (pH-6), presumably to insert into the
      endosome membrane, before being translocated via a process which also requires
      cytosolic ATP hydrolysis. DT translocation is directly triggered and energized by
      the endosome-cytosol pH gradient. Using conjugates with dihydrofolate reductase
      we could indirectly show that ricin and PE require unfolding for translocation. A
      deletion approach enabled to produce a more cytotoxic PE mutant by increasing its
      translocation activity.

PMID- 11833461
TI  - [Regulation of carbohydrate metabolism by insulin: role of transcription factor
      SREBP-1c in the hepatic transcriptional effects of the hormone].
AB  - A number of tissues such as the brain must be continuously provided with glucose
      to meet their energy demand. In contrast, carbohydrate absorption during meals is
      a discontinuous process. Thus, we must store glucose when its is provided,
      release it or spare it when it is less abundant. Insulin, secreted by the
      pancreatic beta-cell is a key hormone in the adaptations of metabolic pathways
      linked to glucose homeostasis. It inhibits hepatic glucose production, promotes
      glucose storage in the liver and glucose uptake and storage in muscles and
      adipose tissues. This is achieved through the modifications of the activity of
      existing proteins (enzymes, transporters) but also through the regulation of gene
      expression. In the liver, when the diet is rich in carbohydrates, insulin is
      secreted and stimulates the expression of genes involved in glucose utilization
      (glucokinase, L-pyruvate kinase, lipogenic enzymes) and inhibits genes involved
      in glucose production (phosphenolpyruvate carboxykinase). The mechanisms by which
      insulin controls the expression of these genes were poorly understood. Recently,
      the transcription factor Sterol Regulatory Element Binding Protein-1c (SREBP-1c)
      has been proposed as a key mediator of insulin transcriptional effects. Insulin
      increases the synthesis and nuclear abundance of this factor which when
      overexpressed in the liver mimics the effects of insulin on insulin-sensitive
      genes. This suggests that SREBP-1c could be involved in pathologies such as type
      2 diabetes, obesity and more generally in insulin resistance syndromes.

PMID- 11833462
TI  - [Major insulin resistance syndromes: clinical and physiopathological aspects].
AB  - Insulin resistance is a common metabolic disorder. It plays an important role in
      the metabolic syndrome (or syndrome X), type 2 diabetes, obesity and in the
      lipodystrophic syndromes recently described, associated with treatments of HIV
      disease and represent a worrying cardiovascular risk. However, its
      pathophysiology remains poorly understood in these situations. Syndromes of major
      insulin resistance, although rare, allow investigations of the mechanisms leading
      to alterations in the insulin transduction pathways. Mutations of the insulin
      receptor gene have been discovered in rare patients. Therefore alterations at the
      post-receptor level are probably causative in other cases. Furthermore, the role
      of body fat repartition seems determinant in the apparition of insulin
      resistance, as attested by the clinical characteristics of lipodystrophies,
      either congenital or acquired. The two lipodystrophic syndromes which molecular
      defect is identified are the familial partial lipodystrophy of the Dunnigan type,
      due to mutations of the lamin A/C gene, and the congenital generalized
      lipodystrophy, linked to alterations in the protein seipin. However, their
      physiopathology remains mysterious. Lamin A/C is indeed an ubiquitous nuclear
      protein, which is also mutated in a genetic squelettic and/or cardiac myopathy,
      and seipin is a protein of unknown function mainly expressed in brain. Progresses
      in the understanding of these syndromes, in particular lipodystrophies which can
      be considered as caricatural models of the metabolic syndrome, will probably
      allow to clarify the physiopathology of the more common forms of insulin
      resistance.

PMID- 11833463
TI  - [Calcium and bioluminescent probes].
AB  - Ca2+ is an universal second messenger in numerous cell physiological processes.
      Aequorin, a bioluminescent calcium-binding protein is used today as a cellular
      probe to measure and image variations in calcium concentrations. The paper
      describes the characteristics and the use of aequorin as a luminescent calcium
      probe, and the future in the use of this protein for calcium imaging.

PMID- 11833464
TI  - [Validation of the use of aequorin for cytoplasmic free calcium determination by
      chemiluminescence in Streptococcus pneumoniae].
AB  - In the extracellular pathogen Streptococcus pneumoniae, transformable by soluble
      DNA, calcium transport is shown to play a key role for vegetative growth,
      developement of competence for genetic transformation and experimental virulence.
      To get a more precise localisation of Ca2+ in the cell, we cloned the cDNA of
      apoaequorine in the chromosome of Streptococcus pneumoniae. This allowed the
      reconstitution of the acquorine system and chemoluminescence measurements of the
      cytoplasmic free calcium concentration in the bacteria. Intracellular free Ca2+
      is 2 microM at the steady state and can reach 14 microM when calcium is added to
      the bacterial suspension. Increase in free Ca2+ in response to an imposed Ca2+
      gradient depends on the initial velocity (Vi) of the DMB-sensitive Ca2+
      transport, showing that changes in cytoplasmic Ca2+ involve active transport.

PMID- 11833465
TI  - [Modulation of calcium conductance by opioid and anti-opioid peptides].
AB  - In the central nervous system, opening of voltage-gated Ca2+ channels triggers
      the release of neurotransmitters. Numerous membrane receptors, particularly those
      belonging to the superfamily of G-protein coupled receptors modulate, in most
      cases inhibit the activity of these channels. In the present review, we describe
      the modulation of calcium channels by opioid and anti-opioid peptides. Following
      a brief presentation of the opioid system, we describe the characteristics of the
      modulation of calcium channels by opioids. Recent major advances concerning
      neuropeptide FF (NPFF), taken as an example of anti-opioid systems, are reviewed.
      Results from our laboratory demonstrating the anti-opioid activity of NPFF, in
      the modulation of Ca2+ channels in isolated neurones, are described.

PMID- 11833466
TI  - [Calcium oscillations induced by lindane in peritoneal macrophages of mice:
      control by the maturation stage of the macrophage].
AB  - Mouse resident peritoneal macrophages loaded with Fluo-3 were examined for
      changes in cytosolic calcium concentration ([Ca2+]i) after stimulation with gamma
      hexachlorocyclohexane (Lindane or gamma-HCCH). These studies, realized on
      macrophage populations, or single cells, by digital imaging microscopy, sought to
      determine the role of calcium influx on cyclical changes according to maturation
      stages of macrophages. Single cell analysis of [Ca2+]i changes in macrophages,
      after gamma-HCCH exposure in 600 microM extracellular calcium, demonstrated that:
      1) these [Ca2+]i variations were asynchronous oscillations with the same
      frequency (1.7 min-1), and 2) these [Ca2+]i variations in macrophages were not at
      the same [Ca2+]i level. This heterogeneity could be correlated to a cell size
      partition of the macrophage population (10.1 +/- 0.44 and 11.45 +/- 0.43
      microns). In the presence of 100 microM calcium, gamma-HCCH induced a calcium
      influx into the two subpopulations, but the calcium oscillations appeared only in
      small macrophages. In the largest ones, [Ca2+]i slowly decreased back down to the
      basal level. The cell size variation could be correlated to a phenotypic
      heterogeneity, linked to the differenciation stage of the cell. Peroxydase
      activity showed that small macrophages were in fact exudate macrophages and the
      largest ones were resident macrophages. Inhibition of the oscillatory patterns by
      a decrease in the extracellular calcium concentration ([Ca2+]ext) or by lanthanum
      chloride (LaCl3) addition is indicative of the important role of calcium influx
      in the triggering of oscillations. The calcium influx was transient and induced
      inositol phosphate (InsP3) production in macrophages. The maintainance of these
      calcium oscillations depended on calcium mobilization from intracellular calcium
      stores by InsP3, since neomycin and 8-(diethylamino) octyl 3,4,5
      trimethoxybenzoate (TMB-8) abolished the oscillations. gamma-HCCH induced a
      transient calcium entry which triggered phospholipase C activation and the
      associated [Ca2+]i oscillations. However, we showed that differences in cell
      responses were observed in relationship with the differentiation stage of the
      mouse peritoneal macrophages, and with the extracellular calcium concentration.

PMID- 11833467
TI  - [Calcium oscillations and Nod signal transduction in Rhizobium-legume symbiosis].
AB  - Rhizobium nodulation (Nod) factors are lipo-chitooligosaccharides that act as
      symbiotic signals, eliciting a number of key developmental responses in the roots
      of legume hosts. One of the earliest responses of root hairs to Nod factors is
      the induction of sharp oscillations of cytoplasmic calcium ion concentration
      ("calcium spiking"). This response was first characterised in Medicago sativa and
      Nod factors were found to be unable to induce calcium spiking in a nodulation
      defective mutant of M. sativa. The fact that this mutant lacked any morphological
      response to Nod factors raised the question of whether calcium spiking could be
      part of a Nod factor-induced signal transduction pathway leading to nodulation.
      More recently, calcium spiking has been described in a model legume, Medicago
      truncatula, and in pea. When nodulation-defective mutants were tested for the
      induction of calcium spiking in response to Nod factors, three loci of pea and
      two of M. truncatula were found to be necessary for Nod factor-induced calcium
      spiking. These loci are also known to be necessary for Nod factor-induction of
      symbiotic responses such as root hair deformation, nodulin gene expression and
      cortical cell division. These results therefore constitute strong genetic
      evidence for the role of calcium spiking in Nod factor transduction. This system
      provides an opportunity to use genetics to study ligand-stimulated calcium
      spiking as a signal transduction event.

PMID- 11833468
TI  - [Basis for the calcium specificity in the plant response to extracellular
      stimulation].
AB  - The Ca2+ cation is fully recognized as an important intracellular second
      messenger coupling a wide range of extracellular stimuli to characteristic
      responses in plant cells. Such a pleiotropic effect raises questions regarding
      the mechanisms by which the signalling pathways, all of then involving an
      increase in intracellular calcium concentration, can be specific to a given
      stimulus. Here, we present recent results which shed light into different
      concepts which may explain the response specificity in signalling processes, such
      as "the cross-talk between signalling pathways", "the Ca2+ signatures" and "the
      compartmentation of Ca(2+)-signalling".

PMID- 11833469
TI  - [Calcium-dependent pathways involved in the production of cytokines in
      lymphocytes].
AB  - CD4+ T lymphocytes are divided in Th1 cells producing IFN gamma and Th2 cells
      that synthetize IL-4. This paper describes signaling pathways activated following
      T cell receptor (TCR) engagement and emphasizes differences that can account for
      differential cytokine production. This paper focuses on a new signaling pathway
      involved in IL-4 synthesis. This pathway couples the TCR to PKC that controls a
      calcium entry through dihydropyridine sensitive calcium channels. The calcium
      response is sufficient to initiate IL-4 gene transcription. Differing from that
      of IL-4, IFN gamma gene expression always requires MAP-kinase activation in
      addition to a calcium signal.

PMID- 11833470
TI  - [HIV-1 Tat protein induces IL-10 production by human monocytes: implications of
      the PKC and calcium pathway].
AB  - In asymptomatic patients infected by HIV-1, the level of IL-10, a cytokine with
      immunosuppressive activity, is associated with the course of HIV infection
      towards AIDS. We show that HIV-1 Tat, a viral protein secreted by infected cells,
      induces IL-10 production by human peripheral blood monocytes. The analysis of the
      signal transduction pathways strongly suggests that the protein kinase C may play
      an essential role in this induction. Stimulation by Tat induces nuclear
      translocation of the transcription factor NFkB the activation of which seems to
      be necessary for IL-10 production. Using microspectrofluorimetry and confocal
      microscopy, we also show that Tat induces a calcium influx.

PMID- 11833471
TI  - [Neural determination in Xenopus laevis embryos: control of early neural gene
      expression by calcium].
AB  - In amphibian embryos the central nervous system derives from the dorsal region of
      the ectoderm. Molecular studies led to the formulation of the "neural default
      model" in which neural development is under the inhibitory control of members of
      the BMP family. These growth factors also act as epidermis inducers. The neural
      fate is revealed by factors secreted by the Spemann Organizer such as noggin,
      chordin, follistatin, Xnr3 and cerberus which act by blocking BMP signalling. We
      propose a new model for neural cell determination in which a signalling pathway
      controlled by an increase in intracellular calcium suppresses the epidermis fate
      and activates the neural fate instead. This increase in calcium is due to an
      influx through calcium channels of the L-type, expressed in ectodermal cells
      during gastrulation. The possible involvement of a calcium-dependent phosphatase
      (calcineurin) to inhibit the epidermis fate and a calcium-calmodulin kinase
      (CaMkinase II) which activates the neural fate is discussed.

PMID- 11833472
TI  - Web based fund raising: is anyone making any real money?
AB  - A larger number of non-profits are looking to establish a Web presence for the
      first time. The opportunity to reach a large number of potential consumers and/or
      donors with the organization's message has proved too tempting for many to
      ignore.

PMID- 11833473
TI  - Making ePhilanthropy work for your organization.
AB  - As some leading-edge non-profits made initial strides in using the Web as a part
      of their fund-raising efforts, we began to see that ePhilanthropy also meant
      online outreach, e-mail campaigns, advocacy and more. Every day, the early
      adopters have pushed the envelope to redefine this new term.

PMID- 11833474
TI  - 2002 non-profit software guide.

PMID- 11833475
TI  - Complete fund-raising software systems vs. donor databases.
AB  - When evaluating fund-raising software packages, it is important to understand the
      distinctions between them. Not all fund-raising software is created equal. In
      fact, there is a whole new breed of fund-raising software that has just entered
      the market.

PMID- 11833476
TI  - Using a clinical data repository to estimate the frequency and costs of adverse
      drug events.
AB  - As a result of increased attention to medical errors, many institutions are
      contemplating increased use of information technology and clinical decision
      support. We conducted a retrospective analysis to estimate the frequency and cost
      of adverse drug events (ADEs) for inpatients at the University of Virginia.
      Applying published criteria for the detection of potential adverse events, we
      used a clinical data warehouse to identify patients and cases with potential
      ADEs. Again using published criteria, we then estimated the actual number of
      adverse drug events and preventable adverse drug events, as well as their
      attributable costs and excess length of stay. Our results showed a higher
      estimate (10.4-11.5 events per 100 admissions) for ADEs than seen in the ADE
      Prevention Study, highlighting the importance of considering the generalizability
      of published ADE studies to other settings. Our analysis demonstrates that
      retrospective analysis can be an efficient and powerful technique to evaluate
      rules and criteria used to detect ADEs and to assess their impact.

PMID- 11833477
TI  - Accuracy of ICD-9-coded chief complaints and diagnoses for the detection of acute
      respiratory illness.
AB  - ICD-9-coded chief complaints and diagnoses are a routinely collected source of
      data with potential for use in public health surveillance. We constructed two
      detectors of acute respiratory illness: one based on ICD-9-coded chief complaints
      and one based on ICD-9-coded diagnoses. We measured the classification
      performance of these detectors against the human classification of cases based on
      review of emergency department reports. Using ICD-9-coded chief complaints, the
      sensitivity of detection of acute respiratory illness was 0.44 and its
      specificity was 0.97. The sensitivity and specificity using ICD-9-coded diagnoses
      were no different. These properties of excellent specificity and moderate
      sensitivity, coupled with the earliness and electronic availability of such data,
      support the use of detectors based on ICD-9 coding of emergency department chief
      complaints in public health surveillance.

PMID- 11833478
TI  - Neural networks in the assessment of HIV immunopathology.
AB  - Surrogate markers are by definition quantifiable laboratory variables that have
      clinical and biological relevance to disease outcomes. Virologic and immunologic
      surrogate markers have proven useful in following HIV-associated viral burden,
      immune dysregulation, dysfunction and deficiency. Monitoring of sequential
      changes in these markers and their interrelationships may provide significant
      information about viral-host-drug dynamics. The complexity and fluidity of these
      changes necessitates that an efficient means be developed for their monitoring.
      We therefore generated a neural network-based model for assessing host dynamics
      over time and compared its performance with that of a multiple regression model.
      Both modeling approaches were applied to the actual, non-filtered, clinical
      observations on 58 HIV-infected individuals treated consistently with Highly
      Active Anti-Retroviral Therapy (HAART), for a period of over-52 weeks resulting
      in an average of 16 observations per patient throughout this time span. Results
      demonstrated that the neural network was at least as accurate as a multi
      regression model. Since our dataset was modest in size we also believe that
      neural networks warrant further consideration for modeling the complexity of HIV
      host dynamics on larger datasets.

PMID- 11833479
TI  - Physician Order Entry impact on drug turn-around times.
AB  - This paper describes a study of the impact of Physician Order Entry (POE) on
      pharmacy order turn-around times. The study looked at two surgical services,
      Neurosurgery and Transplant, of a large Midwestern academic medical center.
      Pharmacy orders were followed in these units from the time a physician wrote an
      order to the time the patient received the medication. The first part of the
      study tracked pharmacy orders for a two-month period before the implementation of
      POE and the second part of the study tracked pharmacy orders for a two-month
      period after POE had been implemented. The pre- and post-POE pharmacy turn-around
      times were compared. It was expected that the data would show a substantial
      decrease in pharmacy order turn-around times. Our study did, in fact, show a
      significant reduction in this turn-around-time.

PMID- 11833480
TI  - A light knowledge model for linguistic applications.
AB  - Content extraction from medical texts is achievable today by linguistic
      applications, in so far as sufficient domain knowledge is available. Such
      knowledge represents a model of the domain and is hard to collect with sufficient
      depth and good coverage, despite numerous attempts. To leverage this task is a
      priority in order to benefit from the awaited linguistic tools. The light model
      is designed with this goal in mind. Syntactic and lexical information are
      generally available with large lexicons. A domain model should add the necessary
      semantic information. The authors have designed a light knowledge model for the
      collection of semantic information on the basis of the recognized syntactical and
      lexical attributes. It has been tailored for the acquisition of enough semantic
      information in order to retrieve terms of a controlled vocabulary from free
      texts, as for example, to retrieve Mesh terms from patient records.

PMID- 11833481
TI  - The palm as a real-time wide-area data-access device.
AB  - Handheld wireless technologies offer great promise in helping to improve
      healthcare. However, it is not clear whether off-the-shelf wireless networking
      will work as well within medical centers as this technology works outside of the
      medical center. Therefore, we evaluated the coverage of wide-area wireless
      technology within two representative academic medical centers. The study
      determined the rate of connectivity by testing both the Palm VII and the Minstrel
      V modem in a set of locations typically frequented by house staff in their daily
      activities. Within one hospital, connectivity was 59% for OmniSky service, and
      78% for Palm.net. The second hospital's connectivity was over 93% with both
      devices. Differences in connectivity were likely due to the number of rooms
      visited with externally exposed walls, the suburban versus urban location of the
      academic medical center, and the relative location of service transponders. When
      examined by the Johns Hopkins Clinical Devices Laboratory, both devices were
      found to operate without interfering with other hospital equipment.

PMID- 11833482
TI  - An integrated system for significant anaesthetic events monitoring.
AB  - Patient safety assessment in anaesthesia increasingly relies on the monitoring of
      frequent but merely undesirable events, like hypotension. We report on the design
      and implementation of such a monitoring system, where 8032 patients were included
      over a three years period. Thirty two 'Significant Anaesthetic Events' were
      defined and their occurrence was routinely collected for each patient. A total of
      2106 significant anaesthetic events were reported. The data were analysed using
      control charts, which showed that an undesirable event was recorded in 1 out of 4
      interventions. The control chart showed that the incidence of significant
      anaesthetic events was out of the expected boundaries during one month. The
      system sensitivity to change in the frequency of significant anaesthetic events
      was investigated by a controlled intervention, designed to increase the incidence
      of bradycardia by changing anxyolitic medication. During the intervention, the
      incidence of bradycardia doubled, while the incidence of other undesirable events
      was not affected. The system described for the collection of significant
      anaesthetic events was easy to set up, sensitive to changes and provided valuable
      tools in performance monitoring.

PMID- 11833483
TI  - Mapping the UMLS Semantic Network into general ontologies.
AB  - In this study, we analyzed the compatibility between an ontology of the
      biomedical domain (the UMLS Semantic Network) and two other ontologies: the Upper
      Cyc Ontology (UCO) and WordNet. 1) We manually mapped UMLS Semantic Types to UCO.
      One fifth of the UMLS Semantic Types had exact mapping to UCO types. UCO provides
      generic concepts and a structure that relies on a larger number of categories,
      despite its lack of depth in the biomedical domain. 2) We compared semantic
      classes in the UMLS and WordNet. 2% of the UMLS concepts from the Health Disorder
      class were present in WordNet, and compatibility between classes was 48%.
      WordNet, as a general language-oriented ontology is a source of lay knowledge,
      particularly important for consumer health applications.

PMID- 11833484
TI  - Transglutaminase: remembering Heinrich Waelsch.

PMID- 11833485
TI  - Therapeutic monitoring of busulfan in pediatric bone marrow transplantation.
AB  - The aim of this study was to describe busulfan disposition in a pediatric
      population who underwent bone marrow transplantation (BMT). Busulfan administered
      dose was 1 mg/kg every 6 h for 4 days. Plasma determinations were performed after
      the first dosing at 0, 15, 30, 60, 90, 120, 180, 240, 300, and 360 min. A
      noncompartment analysis model for extravascular absorption was used for the
      pharmacokinetic analysis. To obtain the area under the concentration-time curve
      (AUC) within the "therapeutic window" of 1,000-1,200 microM x minutes a busulfan
      dose adjustment Was performed at the fourth dose. Forty-five busulfan
      pharmacokinetic analyses were performed in 34 children. Eleven children had their
      dose adjusted [1.19 +/- 0.14) mg/kg] at the fourth dose and the AUC was monitored
      at the fifth one. The mean AUC +/- SD after the fifth dose (998.1 +/- 189.2
      microM x min) was different (p = .006)from that after the first dose (1 mg/kg)
      (687.63 +/- 166.43 microM x min). Six children had their first AUC into the
      "therapeutic window," 17 children had their dose adjusted [1.2 (+/- 0.22) mg/kg],
      but the "adjusted" AUC was not available. These data suggest that it may be
      reasonable to recommend a busulfan dose of 1.2 mg/kg to achieve the accepted
      therapeutic target in children undergoing BMT.

PMID- 11833486
TI  - Alkaptonuria with atypical joint involvement.

PMID- 11833488
TI  - Proceedings of the National Summit on the Future of Education and Practice in
      Health Management and Policy. February 8-9, 2001.

PMID- 11833487
TI  - Cosmic questions. Proceedings of a conference. April 14-16, 1999. Washington, DC,
      USA.

PMID- 11833489
TI  - Organochlorine and butyltin residues in walleye pollock (Theragra chalcogramma)
      from Bering Sea, Gulf of Alaska and Japan Sea.
AB  - Persistent organochlorine (OC) and toxic butyltin compounds (BTs) were determined
      in walleye pollock (Theragra chalcogramma) collected from Gulf of Alaska, Bering
      Sea and Japan Sea, during 1991 and 1992. Polychlorinated biphenyls (PCBs) and
      dichlorodiphenyltrichloroethane (DDTs) and its metabolites were the most abundant
      compounds ranging up to 3200 and 2500 ng/g on lipid weight, respectively,
      followed by chlordane compounds (CHLs), hexachlorocyclohexane isomers (HCHs) and
      hexachlorobenzene (HCB) in the liver of walleye pollock. Concentrations of HCHs
      and HCB in walleye pollock from these remote areas were higher than those in
      fishes from the western North Pacific and Japanese coastal waters, indicating
      atmospheric transport of these compounds to higher latitude regions such as
      Bering Sea and Gulf of Alaska and/or local input around northern Japan Sea. The
      concentrations of other OCs were generally comparable to those in fishes from
      North Pacific Ocean and Japanese waters but significantly lower than in cod-like
      fishes from North Atlantic and European countries. Among sampling locations,
      walleye pollock from Japan Sea showed higher concentrations of DDTs and HCHs
      compared to fishes from Bering Sea and Gulf of Alaska, suggesting greater input
      of these compounds around Japan Sea. Slower declining trend of DDTs and CHLs and
      an increasing pattern of PCBs concentrations were found in walleye pollock from
      Bering Sea during 1982-1992. This may imply a continuous input of these compounds
      by long-range transport and/or long-term persistency in these cold regions.
      Compared to the fishes from Japan Sea, walleye pollock from Bering Sea and Gulf
      of Alaska showed higher proportions of alpha-HCH and p,p'-DDE in the composition
      of HCH isomers and DDT compounds, respectively. This suggests selective
      transportability of these compounds during long-range transport to higher
      latitude remote areas. Concentrations of tributyltin (TBT) in the muscle of
      walleye pollock ranged from 1.1 to 5.5 ng/g on wet weight. Concentrations of TBT
      in deep-sea walleye pollock from Gulf of Alaska and Bering Sea were lower than
      those in Japan Sea.

PMID- 11833490
TI  - (Electron) microscopic observations on tissue integration of collagen-immobilized
      polyurethane.
AB  - The foreign body reactions to collagen-immobilized polyurethane (PU-CI) films
      during subcutaneous implantation in rats were characterized. The underlying
      concept is that collagen-immobilization will improve the tissue integration.
      Since the method of collagen-immobilization involves the covalent coupling of
      collagen to an acrylic acid (AA) based surface graft, both non-modified PU and PU
      AA were used as controls. Bare PU has a flat surface, whereas both PU-AA and PU
      CI displayed a slightly roughened surface. Implantation showed that PU-CI induced
      early after implantation a far more intense foreign body reaction than PU and PU
      AA. This reaction consisted of increased presence of fibrin, granulocytes and
      macrophages. Roughening of the surface as with PU-AA induced only a small
      increase in fibrin formation and cellular migration. At day 5 the reaction to PU
      CI had slowed down; giant cell formation now slowly started but was decreased
      compared to PU and PU-AA. At day 10 capsules around each type of material looked
      similar, but in contrast to PU. PU-CI films could no longer be dissected from
      their capsules. Only at week 3 this also occurred with PU, at which time point
      again similar capsules with the three materials were observed. At week 6, of the
      three materials PU-CI showed the thinnest capsule with most immediate adherence
      of connective tissue. These results show that collagen-immobilization of PU
      increased the early tissue reaction and therefore the tissue integration. The
      thin capsule observed at 6 weeks may be beneficial in e.g. infectious
      circumstances, when easy access for immune reactions is needed. This, and the
      long-term performance of PU-CI will be a matter of future investigations.

PMID- 11833491
TI  - Alginate as a chondrocyte-delivery substance in combination with a non-woven
      scaffold for cartilage tissue engineering.
AB  - For tissue engineering of cartilage, chondrocytes can be seeded in a scaffold and
      stimulated to produce a cartilage-like matrix. In the present study, we
      investigated the effect of alginate as a chondrocyte-delivery substance for the
      construction of cartilage grafts. E210 (a non-woven fleece of polyglactin) was
      used as a scaffold. When bare' E210 (without alginate and without chondrocytes)
      was implanted subcutaneously in nude mice for 8 weeks. the explanted tissue
      consisted of fat and fibrous tissue only. When E210 with alginate but without
      chondrocytes was implanted in nude mice, small areas of newly formed cartilage
      were found. Alginate seems to stimulate chondrogenesis of ingrowing cells. When
      chondrocytes were seeded in E210, large amounts of cartilage were found,
      independent of the use of alginate. This was expressed by a high concentration of
      glycosaminoglycans (30 microg/mg w.w.) and the presence of collagen type II (1.5
      microg/mg w.w.). Macroscopically the grafts of E210 without alginate were shrunk
      and warped, whereas the grafts with alginate had kept their original shape during
      the 8 weeks of implantation. The use of alginate did not lead to inflammatory
      reactions nor increased capsule formation. In conclusion, the use of alginate to
      seed chondrocytes in E210 does not influence the amount of cartilage matrix
      proteins produced per tissue wet weight. However, it provides retention of the
      graft shape.

PMID- 11833492
TI  - Control of vitamin B12 release from poly(ethylene glycol)/poly(butylene
      terephthalate) multiblock copolymers.
AB  - The release of vitamin B12 (1355 Da) from matrices based on multiblock copolymers
      was studied. The copolymers were composed of hydrophilic poly(ethylene glycol)
      terephthalate (PEGT) blocks and hydrophobic poly(butylene terephthalate) (PBT)
      blocks. Vitamin B12 loaded films were prepared by using a water-in-oil emulsion
      method. The copolymer properties, like permeability, could be varied by
      increasing the PEG-segment length from 300 up to 4,000 g/mol and by changing the
      wt% of PEGT. From permeation and release experiments. the diffusion coefficient
      of vitamin B12 through PEGT/PBT films of different compositions was determined.
      The diffusion coefficient of Vitamin B12 was strongly dependent on the
      composition of the copolymers. Although an increased wt% of PEGT (at a constant
      PEG-segment length) resulted in a higher diffusion coefficient, a major effect
      was observed at increasing PEG-segment length. By varying the copolymer
      composition, a complete release of vitamin B12 in 1 day up to a constant release
      for over 12 weeks was obtained. The release rate could be effectively tailored by
      blending copolymers with different PEG-segment lengths. The swelling and the
      crystallinity of the matrix could explain the effect of the matrix composition on
      the release behavior.

PMID- 11833493
TI  - Evaluation of the in-vitro digestion profiles of long and medium chain glycerides
      and the phase behaviour of their lipolytic products.
AB  - An evaluation of the in-vitro digestion profile and phase behaviour of the common
      formulation lipids Miglyol 812 (medium chain triglyceride, MCT), Capmul MCM
      (C8/C10 monoglyceride/ diglyceride mixture), soybean oil (long chain
      triglyceride, LCT) and Maisine 35-1 (C18 monoglyceride/diglyceride mixture), is
      described. Experiments were conducted using titrimetric, high-performance thin
      layer chromatographic (HPTLC) and ultracentrifugational techniques under model
      fasted and post-prandial intestinal conditions. The rate and extent of digestion
      of the medium chain lipids was greater than the corresponding long chain lipids,
      and independent of bile salt concentration, with complete conversion to
      monoglyceride and fatty acid occurring after 30 min digestion. The long chain
      lipid digests separated into an oily phase (containing undigested triglyceride
      and diglyceride), an aqueous phase (containing bile salt, fatty acid and
      monoglyceride) and a pellet phase (containing approximately 5 mm of fatty acid,
      presumably as an insoluble soap) after ultracentrifugation. Higher proportions of
      long chain fatty acid and monoglyceride were dispersed into the aqueous phase
      with increasing bile salt concentrations. In contrast, medium chain lipolytic
      products separated only into an aqueous phase and a pellet fraction in a bile
      salt-independent manner. The digestion of both the C8/C10 and C18
      monoglyceride/diglyceride lipid mixtures was more rapid than the corresponding
      triglyceride, especially at early time points. This investigation provides
      insight into the relative digestion kinetics of medium chain and long chain
      lipids and provides information regarding the phase behaviour of their lipolytic
      products under conditions modelled on those expected after oral administration.
      The data also provide a background for improved understanding of the potential
      utility of long chain and medium chain lipid-based formulations.

PMID- 11833494
TI  - Immunologic and biologic properties of the primary tumor during prolonged
      neoadjuvant chemoimmunotherapy.
AB  - Patients with locally advanced cancers have a poor prognosis when treated with
      radiotherapy and/or surgery alone. The appearance of distant metastases shortly
      after removal of the primary tumor indicates that micrometastases are already
      present at the time of diagnosis. We observed a favorable outcome in patients
      with locally advanced breast cancer treated with a prolonged regimen of
      neoadjuvant chemotherapy plus granulocyte-macrophage colony-stimulating factor
      (GM-CSF[Leukine]) compared with patients receiving fewer chemotherapy cycles
      prior to surgery and radiotherapy. These results can partly be explained by the
      dose-intensive regimen used, but biologic and immunologic processes inherent to
      the prolonged presence of the primary tumor and its draining lymph nodes might
      also contribute to the beneficial outcome. The effects of the prolonged presence
      of the primary tumor during chemotherapy and GM-CSF administration on the
      antitumor immune response, and more specifically the functional properties of
      dendritic cells and T cells, are currently being investigated in a multicenter
      randomized clinical trial comparing prolonged neoadjuvant chemotherapy plus
      cytokines with a conventional treatment schedule. Aside from investigations
      concerning the immune system, other biologic processes, such as tumor
      angiogenesis, are being investigated at the same time.

PMID- 11833495
TI  - Solid-pseudopapillary tumor of the pancreas: a surgical enigma?
AB  - BACKGROUND: Solid-pseudopapillary tumors (SPTs) of the pancreas have been
      reported as rare lesions with "low malignant potential" occurring mainly in young
      women. This study was designed to define the clinicopathological characteristics
      and the effect of surgical intervention. METHODS: A retrospective review from
      January 1985 to July 2000 was performed. Clinicopathological, operative, and
      survival data were obtained. The Kaplan-Meier method and chi2 analysis were
      performed. All cases were re-reviewed by a senior pathologist. RESULTS: During
      this time, 24 patients were diagnosed as having SPTs (0.9%). Twenty females and
      four males were identified, with a median age of 39 years (range, 12-79). The
      median size of the lesions was 8.0 cm (range, 1-20). Two patients' tumors were
      found to be unresectable at initial presentation because of vascular invasion;
      both patients have remained alive with disease, one for 13 years and the other 1
      year. At a median follow-up of 8 years, one recurrence occurred in 17 patients
      who underwent complete resection. Microscopic margin positive (P = .26), invasion
      of surrounding structures (P = .51), and size >5 cm (P = .20) were not
      significant predictors of survival. Four patients presented with synchronous
      liver metastasis and underwent resection of the primary tumor and the liver
      metastasis, with one patient dying of progression of metastatic disease at 8
      months, another alive with recurrence in the liver at 6 years, and the last two
      alive without evidence of disease at 1 month and 11 years. CONCLUSIONS: SPT
      occurs predominantly in women (82%), although it can occur in men; all age groups
      are affected. Complete resection is associated with long-term survival even in
      the presence of metastatic disease.

PMID- 11833496
TI  - The effect of surgery and radiotherapy on outcome of anaplastic thyroid
      carcinoma.
AB  - BACKGROUND: Anaplastic thyroid carcinoma (ATC) is an aggressive rare tumor. We
      analyzed our experience for prognosis and the effect of surgery and radiotherapy
      on patients with ATC. METHODS: We conducted a retrospective review of all
      patients (n = 67) with ATC treated at a tertiary care center from 1969 to 1999.
      Survivor median follow-up was 51 months. Tumor and patient characteristics and
      therapy were assessed for effect on survival by multivariate analysis. RESULTS:
      Patients presented with a neck mass (99%), change of voice (51%), dysphagia
      (33%), and dyspnea (28%). Surgery was performed in 44 of 67 patients, with 12
      complete resections. The 6-month and 1- and 3-year survival rates were 92%, 92%,
      and 83% after complete resection; 53%, 35%, and 0% after debulking; and 22%, 4%,
      and 0% after no resection, respectively (P < .0001). A radiation dose of >45 Gy
      improved survival as compared with a lower dose (P = .02). Multivariate analysis
      showed that age < or = 70 years, absence of dyspnea or dysphagia at presentation,
      a tumor size < or = 5 cm, and any surgical resection improved survival (P < .05).
      CONCLUSIONS: Candidates for surgery with curative intent for ATC are patients <
      or = 70 years, tumors < or = 5 cm, and no distant disease. Radiotherapy >45 Gy
      improves outcome.

PMID- 11833497
TI  - Cytokine profiles of sentinel lymph nodes draining the primary melanoma.
AB  - BACKGROUND: The sentinel lymph node (SLN) draining the primary melanoma is the
      first echelon node where micrometastasis is established. SLNs may be the initial
      sites of antigen presentation associated with immune responses. METHODS: A
      portion of each SLN from 68 melanoma patients undergoing selective SLN dissection
      was processed for enzyme-linked immunospot (ELISPOT) assay determination of
      interferon gamma (IFN-gamma), interleukin-2 (IL-2), granulocyte macrophage colony
      stimulating factor (GM-CSF), and interleukin-10 (IL-10) secretion. The control
      was the adjacent non-SLN. Lymphocytes were stimulated with staphylococcal
      enterotoxin A (SEA) prior to ELISPOT assay. RESULTS: No significant difference
      was noted in the production of IL-10 between the SLNs and non-SLNs. Significant
      production of IFN-gamma, IL-2, and GM-CSF was noted in the SLNs when compared to
      the non-SLNs in the overall group. Patients with no micrometastasis (n = 60) had
      elevated secretion of all cytokines in the SLNs. However, patients harboring
      lymph node micrometastasis (n = 8) showed no increase of cytokine secretion in
      the SLNs. CONCLUSIONS: Significant Th1 and Th2 response was induced in melanoma
      free SLNs. IMPLICATIONS: SLNs without micrometastasis may be activated by
      submicroscopic cells or soluble tumor antigens, while cytokine production may be
      down-regulated by micrometastasis. Future studies should be directed towards
      identifying the specific SLN T cells recognizing the tumor antigens.

PMID- 11833498
TI  - T-cell receptor gamma: a microsatellite marker for colorectal cancer.
AB  - BACKGROUND: T-cell receptor gamma (TCR-gamma) is involved in maintaining host
      cell integrity and homeostasis of the human immune system. We hypothesize that
      polymorphism of the TCR-gamma complex may be involved in the pathogenesis of
      colorectal cancer. METHODS: The microsatellite markers D7S1818 and D7S2206
      located within the TCR-gamma antigen locus on chromosome 7p were amplified by
      polymerase chain reaction, and genotypes were determined for 22 patients with
      early onset of colorectal cancer (<60 years old) and for 38 population-based
      control subjects. RESULTS: Genotype BC of D7S1818 (P = .049) and haplotype AC of
      D7S1818/D7S2206 (P < or = .003) were associated with colorectal cancer as
      compared with the control population (extended Fisher's exact test). CONCLUSIONS:
      This study identifies a novel genetic and clinical association between TCR-gamma
      and early-onset colorectal cancer. Many young patients do not fulfill the
      criteria for hereditary colorectal cancer syndromes and are therefore not
      identified by established screening programs. Markers such as D7S1818 and D7S2206
      may become useful in the identification of patients at risk of developing
      colorectal cancer and permit earlier therapeutic intervention.

PMID- 11833499
TI  - Where there's smoke...

PMID- 11833500
TI  - Osteoporosis screening by community pharmacists: use of National Osteoporosis
      Foundation resources.
AB  - OBJECTIVES: To assess the feasibility of establishing an osteoporosis screening
      program in rural community pharmacies based on information and resources provided
      by the National Osteoporosis Foundation (NOF), to survey primary care providers
      regarding the usefulness of this screening program, and to recommend strategies
      for pharmacists interested in working with patients at risk for osteoporosis.
      DESIGN AND PARTICIPANTS: Pharmacists and/or nurses enrolled women 65 years of age
      and older into the study, measured calcaneal bone density, administered a
      questionnaire to ascertain subjects' osteoporosis risk factors, and provided NOF
      literature to subjects. With their agreement, women's bone mass data and risk
      factor assessments were provided to primary care providers along with NOF's
      Physician's Guide to Prevention and Treatment of Osteoporosis. These providers
      were surveyed as to whether they found this information useful. SETTING: Five
      independent community pharmacies in rural Wisconsin. RESULTS: We enrolled and
      tested 133 women. Of these, 122 (92%) agreed to have information mailed to their
      primary health care providers. These 57 providers were surveyed and 24 (42%)
      responded; of these 24, 20 (83%) found the information they received useful.
      CONCLUSION: A community pharmacy-based osteoporosis screening program using NOF
      materials was well accepted by physicians. NOF resources and recommendations can
      provide a strong foundation for such programs.

PMID- 11833502
TI  - Amlodipine therapy in pediatric patients with hypertension.

PMID- 11833501
TI  - Alternatives to technetium 99m pentetate for radioaerosol inhalation lung
      imaging.

PMID- 11833503
TI  - Impact of a workplace health and wellness pharmaceutical care service on the
      weight and obesity classification of employees.

PMID- 11833504
TI  - The continuing evolution of American pharmacy practice, 1952-2002.

PMID- 11833505
TI  - Hormone replacement therapy: separating fact from fallacy.

PMID- 11833506
TI  - Seven new biologic agents approved in 2001.

PMID- 11833507
TI  - Institute for Safe Medication Practices: creating a safer health care
      environment.

PMID- 11833509
TI  - Who are your heroes?

PMID- 11833510
TI  - Stress in the pharmacy: changing the experience.

PMID- 11833511
TI  - Prescription technologies: keeping pace.

PMID- 11833512
TI  - Provision of pharmaceutical care services in North Carolina: a 1999 survey.
AB  - OBJECTIVE: To describe the extent of and factors associated with the provision of
      pharmaceutical care services (PCS) and value-added pharmaceutical services (PS)
      by pharmacists in North Carolina, the physical changes made in pharmacies to
      accommodate these services, the nature and extent of prior consent or
      collaborative practice arrangements between North Carolina pharmacists and
      prescribers, and the frequency of reimbursement for PCS. DESIGN: Descriptive
      study based on a mail survey. PARTICIPANTS: Pharmacist-managers at each of the
      2,048 licensed pharmacy sites in North Carolina; a list of licensed pharmacies
      provided by the North Carolina Board of Pharmacy was used as the sampling frame.
      MAIN OUTCOME MEASURES: Pharmacists' reports of PCS and pharmacy demographics.
      RESULTS: Response rate was 40%. More than 30% of respondents provided PCS at
      their site, although only 20% met our more stringent definition of PCS (i.e.,
      ensuring appropriate pharmacotherapy, ensuring patient understanding and
      adherence, and monitoring and reporting patient outcomes). Services were more
      frequently offered by university-affiliated (35%) or independent (32%)
      pharmacies. The median number of patients receiving PCS across all sites was 10
      per week. Diabetes was the most common health problem for which PCS were offered.
      Three variables-weekly prescription volume (positive correlation); number of
      staff pharmacists with advanced training, specifically fellowship training; and
      medical clinic/health maintenance organization setting-were significant
      predictors of the numbers of patients provided PCS. Independent community
      pharmacies were most likely to have private counseling areas and to bill for and
      receive payment for PCS. CONCLUSION: In North Carolina, a substantial number of
      pharmacists provided PCS in 1999 or planned to do so in the near future. However,
      the number of patients receiving PCS was relatively low. Practice setting,
      pharmacist education level, and prescription volume were weakly predictive of the
      number of patients receiving PCS. Pharmacists commonly used prior consent
      arrangements with physicians in their practices, but primarily to facilitate
      generic substitution. Relatively few pharmacists billed for PS or PCS.

PMID- 11833513
TI  - Effects of pharmacist monitoring on patient satisfaction with antidepressant
      medication therapy.
AB  - OBJECTIVE: To examine the effects of pharmacist monitoring on patient
      satisfaction with and adherence to antidepressant medication therapy. DESIGN: In
      this prospective field study, we interviewed patients starting an antidepressant
      after a new prescription was dispensed and again 2 months later. The first
      interview assessed patients' characteristics, antidepressant medication history,
      knowledge of antidepresant medications and their use, and beliefs about
      antidepressant medications. The second interview focused on pharmacist monitoring
      behavior and satisfaction with the antidepressant medication. SETTING AND
      PARTICIPANTS: From 23 community pharmacies, we enrolled 100 patients, 59 of whom
      were taking an antidepressant for the first time. MAIN OUTCOME MEASURES: Patient
      satisfaction with and reported adherence to their antidepressant medication
      regimen. RESULTS: Pharmacist monitoring of patients' antidepressant medication
      use varied. More than 70% of patients reported that pharmacists asked about
      medication concerns; 53% and 54% of patients, respectively, said pharmacists
      encouraged their questions and listened to their concerns; and 32% found
      pharmacists helpful in solving problems related to the antidepressant. Fifty
      seven percent of patients reported feeling better a lot of the time since taking
      the antidepressant, 40% said the antidepressant did not bother them, and 83%
      reported missing doses, adding doses, or stopping the antidepressant during the
      study period. Initial beliefs about antidepressants were a strong predictor of
      patient outcomes. Pharmacist monitoring was predictive of satisfaction and
      adherence for individuals taking an antidepressant for the first time.
      CONCLUSION: Pharmacists can play a critical role in monitoring medication
      concerns at the beginning of use, allowing for problem solving, reinforcement,
      and greater patient satisfaction with and adherence to medication therapy.
      Obstacles to effective pharmacist monitoring and follow-up need to be identified
      and addressed in future improvement efforts.

PMID- 11833514
TI  - Advancing to the next level: a look at PRNs 20 years later.

PMID- 11833515
TI  - Patient satisfaction with pharmaceutical care: update of a validated instrument.
AB  - OBJECTIVE: To develop a questionnaire for measuring patient satisfaction with
      pharmaceutical care and to establish its factorial composition. DESIGN: Single
      intervention, noncomparative, 20-item self-administered questionnaire. SETTING:
      Iowa. PARTICIPANTS: Seven hundred seventy-five prescription patrons of eight
      community pharmacies whose pharmacists had received training in pharmaceutical
      care but who had not yet implemented it. INTERVENTIONS: An instrument originally
      developed to measure patient satisfaction with traditional community pharmacy
      services was modified to focus on the elements of pharmaceutical care. This
      revised questionnaire was mailed to participants. MAIN OUTCOME MEASURES:
      Participant responses to items in the questionnaire. RESULTS: The survey response
      rate was 55%. Factor analysis and item analysis identified two dimensions of
      pharmaceutical care. We labeled the dimensions Friendly Explanation (including
      items related to friendliness of care, the setting of care, and medication
      counseling) and Managing Therapy (items dealing with the concept of
      pharmaceutical care-managing drug therapy and solving therapy problems).
      Respondents scored items on the Managing Therapy scale lower than they did items
      on the Friendly Explanation scale. The scales were highly correlated. Two other
      hypothesized dimensions of care-Consideration/Caring Relationships and Setting
      were subsumed in the final scale of Friendly Explanation. CONCLUSION: The
      instrument provides information on patients' satisfaction with two dimensions of
      pharmacy services. The instrument may be useful to practicing pharmacists, but it
      should be used cautiously until it is tested among patrons of pharmacies known to
      provide different levels of care.

PMID- 11833516
TI  - Collaboration between academics and practitioners: a view from both sides.

PMID- 11833517
TI  - Results of a smoking cessation clinic in community pharmacy practice.
AB  - OBJECTIVES: To describe and assess the effectiveness of a smoking cessation
      clinic. DESIGN: Single group, unblinded study. SETTING: Seven chain (mass
      merchandise) community pharmacies in Virginia. PARTICIPANTS: Forty-eight patients
      who were smokers when admitted to the study. INTERVENTIONS: Fifteen community
      chain pharmacists were trained using a smoking cessation training manual
      developed at the Virginia Commonwealth University School of Pharmacy. From April
      1, 1997, through December 31, 1999, interested patients met individually with a
      study pharmacist during scheduled clinic times in semiprivate counseling areas. A
      patient chart was maintained at the site and updated after each visit. The first
      30 patients completed a questionnaire after the third visit to the smoking
      cessation clinic to assess satisfaction with pharmacists and the overall program.
      MAIN OUTCOME MEASURE: Rate of long-term smoking cessation. RESULTS: Of the 48
      patients, 12 (25.0%) abstained from smoking cigarettes for 12 months or more
      beyond their predetermined quit dates. Abstinence rates for 1, 3, and 6 months
      were 43.8%, 31.3%, and 25.0%, respectively. Women were nearly five times more
      successful in attaining long-term abstinence than were men (33.3% versus 6.7%; P=
      .047). No significant differences were observed in cessation rates related to
      age, number of cigarettes smoked per day, level of nicotine dependence, number of
      previous quit attempts, or method of cessation. Increased appetite and weight
      gain were the most frequently reported withdrawal symptoms (16.7% of patients).
      Patients expressed satisfaction with the pharmacists and the smoking cessation
      program. CONCLUSION: Compared with other types of previously reported
      interventions, a community pharmacist-managed smoking cessation clinic achieved
      greater long-term smoking cessation rates.

PMID- 11833519
TI  - Success during these trying times.

PMID- 11833518
TI  - In-house preparation of technetium 99m-labeled human serum albumin for evaluation
      of protein-losing gastroenteropathy.
AB  - OBJECTIVE: To develop an in-house preparation method for technetium 99m-labeled
      human serum albumin (99mTc-HSA) to meet the clinical need for gastrointestinal
      (GI) protein loss evaluation in our institution. DESIGN/SETTING: Our in-house HSA
      was prepared by slowly adding 2 mL of 25% HSA to 50 mL nitrogen-purged,
      sterilized water. We then continued the nitrogen purging process for another 15
      minutes before adding 0.5 mL of stannous chloride (SnCl2) in concentrated
      hydrochloride (40 mg/mL) to the HSA solution. Next, we transferred 1 mL of the
      mixture to a 5 mL vial containing 0.5 mL of 30 mCi (1,110 MBq) 99mTc. Using a
      paper chromatography method during a 6-hour postpreparation time period, we
      evaluated the effects of filtration (0.2 microm membrane filter versus no
      filtration) and storage temperature (25 degrees C versus 37 degrees C) on the in
      vitro stability of 99mTc-HSA. PATIENTS OR OTHER PARTICIPANTS: In this study, we
      employed the in-house 99mTc-HSA preparation to study GI protein loss in two
      patients. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: We used a
      radiochemical purity (RCP) value of not less than 90% as the index for
      determining in vitro stability of the in-house 99mTc-HSA preparation. The nuclear
      medicine physician interpreted the image to determine the location and extent of
      protein loss in the GI tract. RESULTS: Our results demonstrate that the overall
      RCP of 99mTc-HSA was 95.0% +/- 2.2% (mean +/- SD). We found no statistically
      significant difference in RCP value between filtered and nonfiltered 99mTc-HSA
      preparations across the sampled time points. However, RCP values tended to
      increase with time for each of the temperature-controlled preparations (P < .01).
      Storage temperature had a significant effect (P < .01), with refrigerated samples
      having an estimated 2.2% lower RCP value across time. However, the difference
      between room temperature and refrigerated samples decreased over time (P < .02)
      to only 1.1% at the 6-hour sampling. We noted gradual accumulation of 99mTc-HSA
      within the first hour in one patient, and the imaging results indicate that both
      patients had protein-losing enteropathy. CONCLUSION: It is relatively easy to
      prepare 99mTc-HSA in-house, achieving a high RCP level as well as extended in
      vitro stability. The clinical data further indicate that our in-house preparation
      of 99mTc-HSA may be useful for the study of GI protein loss; however, further
      clinical evaluation is needed.

PMID- 11833520
TI  - Improving cardiovascular health in postmenopausal women by addressing medication
      adherence issues.
AB  - OBJECTIVE: To review medication adherence issues that relate to managing
      cardiovascular health in postmenopausal women and to explore strategies
      pharmacists can use to improve outcomes by identifying and resolving adherence
      problems. DATA SOURCES: Published articles identified through MEDLINE using the
      search terms adherence, compliance, cardiovascular, and menopause. Additional
      articles and data were identified from the bibliographies of the retrieved
      articles and from Web sites and reports from the National Council on Patient
      Information and Education, North American Menopause Society, American College of
      Obstetricians and Gynecologists, and American Heart Association. DATA SYNTHESIS:
      Cardiovascular disease is the leading killer of women, a fact many women do not
      recognize. Although effective pharmacologic treatments for managing risk factors
      for cardiovascular disease have been developed, these therapies are
      underprescribed, and patient adherence to them is often poor. Efforts to increase
      postmenopausal women's awareness of cardiovascular disease and the efficacy of
      therapeutic regimens can help improve such patients' adherence to these
      lifesaving treatments. CONCLUSION: As one of the most accessible health care
      professionals, pharmacists are well positioned to provide counseling about the
      importance of medication adherence, help measure and optimize outcomes from
      medication use, and help patients find objective and authoritative sources of
      information about their conditions. By working with postmenopausal women to
      enhance their adherence, pharmacists can help them improve their cardiovascular
      health.

PMID- 11833521
TI  - Meeting the therapeutic challenge of the patient with osteoarthritis.
AB  - OBJECTIVE: To discuss the diagnosis of osteoarthritis and the efficacy of
      available pharmacologic and nonpharmacologic treatment options. DATA SOURCES:
      Published reports on the diagnosis and treatment of osteoarthritis were
      identified through a MEDLINE search of English-language journal articles using a
      focused title search for the keywords acetaminophen, nonsteroidal anti
      inflammatory, COX-2 nonsteroidal, opioids, capsaicin, tramadol, glucosamine,
      hyaluronic acid, and osteoarthritis and by reviewing the bibliographies of
      selected reviews. The American College of Rheumatology (ACR) guidelines, as
      updated in September 2000, for the treatment of osteoarthritis of the hip and
      knee were analyzed with appropriate references to clinical and scientific
      studies, review articles, and other published guidelines. DATA SYNTHESIS: Each
      patient's medical history and level of pain should decide the most appropriate
      treatment. Nonpharmacologic therapies should always be included in the treatment
      regimen. If further pain management is required, the most appropriate
      pharmacologic treatments are acetaminophen or nonsteroidal anti-inflammatory
      drugs for mild-to-moderate pain, tramadol or opioid combinations for moderate-to
      moderately severe pain, and opioids for severe pain. Adjunctive treatments,
      intraarticular injections, and surgery are also viable options for some patients.
      CONCLUSION: If used properly, the ACR guidelines for the treatment of
      osteoarthritis are important tools in the care of the patient with this disease.

PMID- 11833522
TI  - Changes in JAPhA's peer review system.

PMID- 11833523
TI  - Development and implementation of a smoking cessation clinic in community
      pharmacy practice.
AB  - OBJECTIVE: To describe a pharmacist-operated program to help people stop smoking.
      SETTING: Community chain (mass-merchandise) pharmacy practice sites in Virginia.
      PARTICIPANTS: Faculty at the Virginia Commonwealth University School of Pharmacy
      (VCU) and 15 practicing pharmacists. PRACTICE DESCRIPTION: Smoking cessation
      clinics within the pharmacy departments of seven Target stores. PRACTICE
      INNOVATION: With input from the practicing pharmacists and using the most current
      strategies reported in the literature, faculty at VCU developed a training manual
      for smoking cessation counseling. This manual was used to facilitate a 4-hour
      training session and also served as a resource for pharmacists in the smoking
      cessation clinics. Pharmacists were taught about behavioral modifications, the
      Transtheoretical Model of Change as applied to smoking cessation, documentation,
      the Fagerstrom Test for Nicotine Dependence, smoking cessation therapies, patient
      counseling techniques, physical assessment skills, and how to develop an
      individualized action plan for smoking cessation. As pharmacists established
      smoking cessation clinics, issues such as workflow, continuous quality
      improvement, and marketing were addressed by the faculty members and
      practitioners. RESULTS: Using the process and tools described in this article,
      pharmacists successfully established and operated smoking cessation clinics.
      CONCLUSION: The process and materials developed for this demonstration project
      can serve as templates for other pharmacy faculty members and community
      pharmacists who wish to offer smoking cessation clinics.

PMID- 11833524
TI  - Combination therapy for non-Hodgkin's lymphoma: an opportunity for pharmaceutical
      care in a specialty practice.
AB  - OBJECTIVE: To describe the application of pharmaceutical care practices in the
      administration of new therapeutic radiopharmaceuticals used in the treatment of
      non-Hodgkin's lymphoma (NHL). PRACTICE DESCRIPTION: At the Antibody Labeling
      Facility at the University of Nebraska Medical Center, the nuclear pharmacist
      provides support in the formulation, preparation, and quality testing of
      radiopharmaceuticals. The nuclear pharmacist also provides direct patient care by
      assisting in the administration of radiopharmaceuticals, monitoring patients
      during their infusions, and counseling patients on radioimmunotherapy and
      radiation safety. PRACTICE INNOVATION: Expanding the role of the nuclear
      pharmacist in treating patients with NHL using radiolabeled monoclonal antibodies
      (MABs). INTERVENTIONS: The nuclear pharmacist provides specialized pharmaceutical
      care by being involved in planning patient care, administering diagnostic and
      therapeutic radiopharmaceuticals, performing individualized patient dose
      calculations, monitoring patients, and counseling patients. MAIN OUTCOME
      MEASURES: Number of patients treated with radiolabeled MABs. RESULTS: Since
      January 1996, 85 patients with NHL have been treated using 131I-tositumomab
      (Corixa, GlaxoSmithKline), an anti-B1 MAB, under various clinical research
      protocols requiring specialized pharmaceutical care. The nuclear pharmacist on
      the team provided direct patient care, assisting with the administration of
      diagnostic and therapeutic radiopharmaceuticals under a collaborative agreement
      with a nuclear medicine physician or a radiation oncologist. Other pharmaceutical
      care activities performed include calculating individual patient doses, obtaining
      medication histories, counseling patients on their therapy and on radiation
      safety after early release, and monitoring patients for adverse effects during
      medication infusion. Patients have responded favorably to nontraditional nuclear
      pharmacy activities. CONCLUSION: The nuclear pharmacist has become an important
      member of the health care team that provides a new and unique therapy for
      patients with NHL. To date, the nuclear pharmacist, in collaboration with the
      nuclear medicine physician or the radiation oncologist, has successfully
      administered the tositumomab and 131I-tositumomab combination therapy without
      significant incident.

PMID- 11833525
TI  - Primary bacterial enteritis caused by Providencia alcalifaciens in three dogs.

PMID- 11833526
TI  - Use of allometry in predicting anatomical and physiological parameters of
      mammals.
AB  - One challenge for veterinarians, animal facilities and research scientists is the
      making of physiological estimates appropriate to a variety of species for which
      data are often either completely lacking or are incomplete. Our intent in
      compiling the data in this paper is to provide the best possible database of
      normal physiological and anatomical values primarily (though not exclusively) for
      four common mammalian model species: mouse, rat, dog and man. In order to make
      those data as accessible and applicable as possible, we have presented the
      results of this study in the form of body-size dependent allometric equations in
      which some variable (Y) is expressed as a dependent function of body mass (M) in
      the power-law equation, Y = aM(b). By compiling these data, it is apparent that
      the resultant equations are quantitatively grouped (with similar slope or 'b'
      values). These emergent patterns provide insights into body-size dependent
      'principles of design' that seem to dictate several aspects of design and
      function across species among all mammals. In general, the weights of most
      individual organs scale as a constant fraction of body mass (i.e. the body mass
      exponent, b approximately equal to 1.0). Biological rates (e.g. heart rate,
      respiratory rate) scale as b approximately equal to -1/4. Finally, volume-rates
      (the product of volume and rate) such as cardiac output, ventilation and oxygen
      uptake vary as b approximately equal to 3/4.

PMID- 11833527
TI  - The impact of the introduction of the ethical review process for research using
      animals in the UK: implementation of policy.
AB  - Nearly all establishments in the UK regulated under the Animals (Scientific
      Procedures) Act 1986 had introduced an ethical review process (ERP) within 9
      months of its formal requirement, although quite a high proportion of more junior
      staff were not familiar with it. A significant proportion of those questioned
      believed that the ERP has improved the quality (particularly the ethical quality)
      of project licences. A smaller proportion of respondents believed that the ERP
      has had a beneficial impact on animal work and training. Nearly all the
      respondents viewed animal care and accommodation as good or excellent.

PMID- 11833528
TI  - The effects of prior growth as a biofilm on the virulence of Salmonella
      typhimurium for mice.
AB  - Relatively little is known about how growth as a biofilm affects the virulence of
      pathogenic bacteria. In this study, the virulence of Salmonella typhimurium grown
      as a biofilm, or as planktonic cells, was compared in mice. Increased numbers of
      colony forming units were recovered from the spleens of mice 5 days after i.p.
      injection with S. typhimurium grown as a biofilm, as compared with planktonic
      cells (P < 0.05). No significant difference in the CFU of S. typhimurium
      recovered from the liver was noted at the same time point, and no difference was
      noted in the CFU recovered from the spleen or liver at 5 days after i.v. or i.g.
      inoculation with 10(5) S. typhimurium. Nor were any differences noted at 7 days
      after i.p., i.v. or i.g. inoculation. Thus, any effect of growth as a biofilm has
      on the virulence of S. typhimurium seems to be limited to the first 5 days after
      i.p. inoculation.

PMID- 11833529
TI  - Microbial diversity of a mesophilic hydrogen-producing sludge.
AB  - A hydrogen-producing sludge degraded 99% of glucose at 36 degrees C and pH 5.5,
      producing a methane-free biogas (comprising 64% hydrogen) and an effluent
      comprising mostly butyrate, acetate, and ethanol. The yield was 0.26 l H2 g(-1)
      glucose and the production rate per gram of volatile suspended solids was 4.6 1
      H2 day(-1). A 16S rDNA library was constructed from the sludge for microbial
      species determination. A total of 96 clones were selected for plasmids recovery,
      screened by denaturing gradient gel electrophoresis, and sequenced for rDNA.
      Based on the phylogenetic analysis of the rDNA sequences, 64.6% of all the clones
      were affiliated with three Clostridium species (Clostridiaceae), 18.8% with
      Enterobacteriaceae, and 3.1% with Streptococcus bovis (Streptococcaceae). The
      remaining 13.5% belonged to eight operational taxonomic units, the affiliations
      of which were not identified.

PMID- 11833530
TI  - Vacuum-soaking of wood chip shiitake (Lentinula edodes) logs to reduce soak time
      and log weight variability and to stimulate mushroom yield.
AB  - Synthetic logs were vacuum-soaked or regular-soaked to determine the effects of
      soaking on yield and mushroom size, log weight variability and water distribution
      within the log. Yields (g/log) from substrates vacuum-soaked were higher by
      26.7%, 18.6% and 35.8% (mean = 27.2%) for crops I, II and III, respectively, when
      compared with regular-soaked. However, mushroom size averaged only 11.2 g for
      vacuum-soaked logs vs 17 g for regular-soaked logs (51.8% larger for regular
      soaked). The time required for vacuum-soaking logs was generally less than 3 min,
      compared with regular-soaking times ranging over 3-15 h. Water tended to
      accumulate more in the outside zone in the vacuum-soaked logs, compared with
      regular-soaked logs. Mean moisture contents for crops I and II for outside,
      middle and interior zones of vacuum-soaked logs were 66%, 47.5% and 42.2%,
      respectively, while regular-soaked logs for the same zones were 62.4%, 52.1% and
      50.9%, respectively. Vacuum-soaked log weights had lower standard deviations than
      weights for regular-soaked logs in four out of six soaks, indicating a more
      uniform soaking process.

PMID- 11833531
TI  - Production of teicoplanin by valine analogue-resistant mutant strains of
      Actinoplanes teichomyceticus.
AB  - Teicoplanin is a glycopeptide antibiotic produced by Actinoplanes
      teichomyceticus. A strain improvement to increase the productivity of the major
      component, teicoplanin A2-2, was carried out. As the fatty moiety of teicoplanin
      A2-2 is derived from L-valine, L-valine analogue (valine hydroxamate)-resistant
      mutants were derived. One of the mutants, 98-1-227, overproduced valine and
      produced a higher titer of total teicoplanin with higher A2-2 content. In a pilot
      fermentor (7 m3), the total productivity of teicoplanin was 1,800 units/ml and
      the A2-2 content was 58%.

PMID- 11833532
TI  - Dereplication for biotechnology screening: PyMS analysis and PCR-RFLP-SSCP (PRS)
      profiling of 16S rRNA genes of marine and terrestrial actinomycetes.
AB  - The search for exploitable biology is a major task for biotechnology-based
      industries. In this context, discrimination between previously tested or
      recovered micro-organisms (dereplication) is imperative, in order to reduce
      screening costs by sorting large collections of isolates, which are then
      subjected to further detailed evaluation. Pyrolysis mass spectrometry (PyMS) is a
      whole-cell fingerprinting technique that enables the rapid and reproducible
      sorting of micro-organisms, uses small samples and has the advantage of being
      fully automated. In this study, we compare chemometric fingerprinting with a
      ribotyping fingerprinting method, in order to investigate the extent to which
      pyrogroups formed by PyMS analysis relate to genetic diversity, using polymerase
      chain reaction-restriction fragment length polymorphism-single-strand
      conformational polymorphism (PRS). A mixture of environmental strains of mycolic
      acid containing actinomycetes was used to mimic the selection of colonies from
      primary isolation plates. The congruence found between the clusters defined by
      the chemometric and molecular fingerprinting techniques was very high and
      demonstrated the effectiveness of PyMS as a rapid sorting and dereplicating
      procedure for putatively novel strains, criteria that are critical for
      biotechnological screens. Moreover, PyMS analysis revealed significant variation
      within pyrogroups that contained strains with the same genotypic (PRS)
      characteristics, thus emphasising its discriminatory capacity at the infraspecies
      level.

PMID- 11833533
TI  - Effect of inclusion of defatted grape seed meal in the diet on digestion and
      performance of growing rabbits.
AB  - The digestion and nutritive value of defatted grape seed meal (DGSM) was
      investigated. A basal diet was formulated to meet requirements of growing
      rabbits. Another diet was formulated by substituting 15.2% of the basal diet with
      DGSM. Two hundred eight weaned 30-d-old rabbits were fed these diets, and
      fattening performance was recorded. Eighty animals were used to study the effect
      of DGSM inclusion on cecal fermentation traits and intestinal disaccharidase
      activity at two ages (5 and 35 d after weaning). Fecal apparent digestibility of
      nutrients was measured in 18 rabbits. A third diet was formulated to contain DGSM
      (61.3%) as the sole source of fiber and a supplement consisting of wheat flour,
      casein, lard, and a mixture of vitamins and minerals to avoid nutrient
      imbalances. This semipurified diet was used to determine cecal digestion traits,
      disaccharidase activity in the small intestine, fecal apparent digestibility of
      nutrients, and rate of passage in 70-d-old rabbits. Digestible energy and NDF and
      CP digestibilities of DGSM calculated by difference were 5.51 +/- 0.89 MJ/kg DM,
      24.5 +/- 5.76%, and 46.8 +/- 14.9%, respectively. Inclusion of 15% of DGSM in the
      basal diet increased ADFI in finishing rabbits (from 9 to 15%; P < 0.05), so that
      DE intake increased although dietary DE concentration decreased. As a
      consequence, ADG increased by 3.3% in the whole fattening period (P = 0.046). The
      increase in ADFI was parallel to an 8% decrease in the weight of cecal contents
      (P = 0.059), and it was in agreement with the relatively short cecal mean
      retention time of DGSM (7.61 h) in the semipurified diet. Inclusion of 15% of
      DGSM in the basal diet did not affect (P > or = 0.20) mortality (10.1%) or cecal
      concentrations of VFA, NH3 N, or cecal pH either at 5 d (71.9 mM, 17.7 mM, and
      5.75, respectively) or at 35 d after weaning (74.6 mM, 10.1 mM, and 5.66,
      respectively) but improved the sucrase activity in the ileum by 36% (P = 0.031).
      Digestibility of NDF of DGSM in the semipurified diet was 8.57%, which agrees
      with the low acidity and weight of cecal contents of animals fed this diet (6.26
      and 3.63% BW, respectively). From these results, we conclude that DGSM has a
      relatively high DE concentration and its inclusion at moderate levels (15%) in
      the diet exerts a positive effect on ADFI, DE intake, and ADG with no impairment
      of cecal fermentation and mortality.

PMID- 11833534
TI  - Growth performance, carcass characteristics, nutrient digestibility and fecal
      odorous compounds in growing-finishing pigs fed diets containing hydrolyzed
      feather meal.
AB  - This study was designed to determine the effects of hydrolyzed feather meal
      inclusion on growth performance, carcass characteristics, nutrient digestibility
      and fecal odorous compounds in modern lean growth genotype pigs. Two hundred
      forty pigs (BW = 23.2 +/- 1.3 kg) were allotted based on BW and sex to a 2 x 6
      factorial arrangement of treatments (four pens per treatment; five pigs per pen)
      in a randomized complete block design. Factors consisted of 1) sex (barrows or
      gilts) and 2) dietary treatment (0, 2, 4, 6, 8, or 10% hydrolyzed feather meal).
      Diets were formulated to contain 1.00, 0.90, 0.75, or 0.60% apparent ileal
      digestible lysine for phases 1 to 4, respectively, with other amino acids
      provided at an ideal ratio. Available P and ME were kept constant within each
      phase. No significant interactions between feather meal inclusion and sex were
      observed for growth performance (P > 0.15). Body weight gain was reduced (P <
      0.05) for pigs fed 10% feather meal compared to pigs fed 0, 4, or 8% feather
      meal. Feed intake of pigs fed 10% feather meal was reduced (P < 0.05) compared to
      pigs fed 0 or 4% feather meal. Ultrasound backfat measurements tended (P = 0.12)
      to increase with increasing levels of feather meal. Daily lean gain was less (P <
      0.05) in pigs fed 10% feather meal than in pigs fed either 0, 2, 4, or 8% feather
      meal. Digestibility of N measured on wk 9 decreased quadratically (P < 0.001)
      with increasing levels of feather meal. Phosphorus digestibility increased in a
      linear fashion (P < 0.02), however, the improvement in P digestibility with
      increasing levels of feather meal was more pronounced in barrows compared to
      gilts (interaction, P < 0.05). Fecal samples obtained from pigs fed 0, 4, or 8%
      feather meal were analyzed for odorous compounds. Concentrations of butanoic,
      pentanoic, and 3-methylbutanoic acid were greater (P < 0.05) and concentrations
      of 3-methylphenol, 4-methylphenol, indole, and decane were less (P < 0.05) in
      feces from pigs fed feather meal. These results suggest that feather meal can be
      included in diets for growing-finishing pigs at a rate of 8%. Excretion of N in
      feces increased but P excretion decreased with increasing levels of feather meal.
      Odorous compounds in feces can be affected by the inclusion of hydrolyzed feather
      meal, but the exact impact of these changes on odor perception remains to be
      elucidated.

PMID- 11833535
TI  - A dynamic model of N metabolism in the lactating dairy cow and an assessment of
      impact of N excretion on the environment.
AB  - Improving N utilization in dairy cows and especially reducing N output in excreta
      is desirable due to global concerns of agricultural contribution of N to
      environmental pollution, particularly as ammonia. Data from five N balance
      experiments were used to develop a dynamic model that was evaluated with
      independent data. Model predictions of feces, urine, and milk outputs were close
      to observed values. Statistical analysis showed that 96% of mean square
      prediction error for feces and urine N output predictions was due to random
      variation. However, the model tends to overpredict milk N output, especially at
      higher N intake levels. Evaluation of model predictions for independent
      experimental observations from Agricultural Development Advisory Service at
      Bridgets (U.K.) showed good agreement between predicted and observed urine N
      output (95% due to random variation). However, there was a slight underprediction
      for fecal N output (14% mean square prediction error due to bias) and
      overprediction of milk N output (22% of mean square prediction error due to
      bias). The model predictions of N outputs in excreta were sensitive to changes in
      energy concentration of the diet. Dietary protein degradability had only a small
      influence on predicted fecal N output. However, the model was sensitive in its
      predictions of urine N when protein degradability was varied. Application of the
      model to assess reduction in ammonia emissions from dairy cows showed that
      increasing the energy concentration could potentially reduce ammonia emissions by
      up to 25% per cow. Similarly, reducing CP concentration in the diet to about 16%
      could reduce ammonia production by 20% and lower degradability of CP to match
      microbial requirement by 19% per cow. The model is a first step toward a
      mechanistic approach of nutrient modeling, and it is a valuable method for
      predicting N excretions and estimating N emissions from dairy systems.

PMID- 11833536
TI  - Scaling to account for heterogeneous variances in a Bayesian analysis of broiler
      quantitative trait loci.
AB  - A Bayesian method for QTL analysis that is capable of accounting for
      heterogeneity of variance between sexes, is introduced. The Bayesian method uses
      a parsimonious model that includes scaling parameters for polygenic and QTL
      allelic effects per sex. Furthermore, the method employs a reduced animal model
      to increase computational efficiency. Markov Chain Monte Carlo techniques were
      applied to obtain estimates of genetic parameters. In comparison with previous
      regression analyses, the Bayesian method 1) estimates dispersion parameters and
      polygenic effects, 2) uses individual observations instead of offspring averages,
      and 3) estimates fixed effect levels and covariates and heterogeneity of variance
      between sexes simultaneously with other parameters, taking uncertainties fully
      into account. Broiler data collected in a feed efficiency and a carcass
      experiment were used to illustrate QTL analysis based on the Bayesian method. The
      experiments were conducted in a population consisting of 10 full-sib families of
      a cross between two broiler lines. Microsatellite genotypes were determined on
      generation 1 and 2 animals and phenotypes were collected on third-generation
      offspring from mating members from different families. Chromosomal regions that
      seemed to contain a QTL in previous regression analyses and showed heterogeneity
      of variance were chosen. Traits analyzed in the feed efficiency experiment were
      BW at 48 d and growth, feed intake, and feed intake corrected for BW between 23
      and 48 d. In the carcass experiment, carcass percentage was analyzed. The
      Bayesian method was successful in finding QTL in all regions previously detected.

PMID- 11833537
TI  - Evidence that comodulation detection differences depend on within-channel
      mechanisms.
AB  - The threshold for detecting a narrow-band noise signal in the presence of one or
      more masking noise bands is higher when the signal and masker bands have the same
      envelope (i.e., are comodulated) than when they have independent envelopes. This
      is called a comodulation detection difference (CDD). CDD might be caused by
      perceptual grouping of the signal and masker bands when they are comodulated.
      This hypothesis leads to the prediction that some masking should occur for
      comodulated bands, even when they are widely separated in frequency. An
      alternative hypothesis is that CDD occurs because, when the signal and masker
      bands are independent, the signal band can be detected in the dips of the masker
      envelope. This leads to the prediction that CDD should only occur when the masker
      produces significant excitation at the signal place. Experiment 1 tested these
      predictions in a paradigm similar to two-tone masking. The signal was a 20-Hz
      wide noise centered at 1500 Hz, and the masker consisted of two bands of noise on
      either side of the signal frequency, whose envelopes were either comodulated
      (condition C) or uncorrelated (condition U) with the envelope of the signal band.
      In a third condition (S), the signal band was replaced by a sinusoid. The
      frequency separation between the signal and masker bands, delta f, was varied
      from 100 to 1400 Hz. Thresholds were very similar for conditions U and S;
      thresholds declined progressively as delta f increased beyond 200 Hz, and reached
      the absolute threshold for delta f = 1400 Hz. For values of delta f from 200 to
      1000 Hz, thresholds were higher for condition C than for conditions U or S (i.e.,
      a CDD occurred), but for delta f = 1400 Hz thresholds for condition C also
      reached absolute threshold. In experiment 2, delta f was fixed at 600 Hz and
      conditions were included where only the upper or the lower masker band was
      correlated with the signal band. Also, the overall level of the masker was
      systematically varied. The results indicate that the magnitude of CDD is
      determined by the comodulation of the signal band with the masker band producing
      the most masking. Overall, the results support an explanation based on the spread
      of excitation and dip listening, rather than an explanation based on perceptual
      grouping.

PMID- 11833538
TI  - Detection of frequency modulation by hearing-impaired listeners: effects of
      carrier frequency, modulation rate, and added amplitude modulation.
AB  - It has been proposed that the detection of frequency modulation (FM) of
      sinusoidal carriers can be mediated by two mechanisms: a place mechanism based on
      FM-induced amplitude modulation (AM) in the excitation pattern, and a temporal
      mechanism based on phase-locking in the auditory nerve. The temporal mechanism
      appears to be "sluggish" and does not play a role for FM rates above about 10 Hz.
      It also does not play a role for high carrier frequencies (above about 5 kHz).
      This experiment examined FM detection in three young subjects with normal hearing
      and four elderly subjects with cochlear hearing loss. Carrier frequencies were
      0.25, 0.5, 1, 2, 4, and 6 kHz and modulation rates were 2, 5, 10, and 20 Hz. FM
      detection thresholds were measured both in the absence of AM, and with AM of a
      fixed depth (m = 0.33) added in both intervals of a forced-choice trial. The
      added AM was intended to disrupt cues based on FM-induced AM in the excitation
      pattern. Generally, the hearing-impaired subjects performed markedly more poorly
      than the normal-hearing subjects. For the normal-hearing subjects, the disruptive
      effect of the AM tended to increase with increasing modulation rate, for carrier
      frequencies below 6 kHz, as found previously by Moore and Sek [J. Acoust. Soc.
      Am. 100, 2320-2331 (1996)]. For the hearing-impaired subjects, the disruptive
      effective of the AM was generally larger than for the normal-hearing subjects,
      and the magnitude of the disruption did not consistently increase with increasing
      modulation rate. The results suggest that cochlear hearing impairment adversely
      affects both temporal and excitation pattern mechanisms of FM detection.

PMID- 11833539
TI  - Low-frequency reflection characteristics of the s0 lamb wave from a rectangular
      notch in a plate.
AB  - An analysis of the reflection of the fundamental Lamb mode s0 from surface
      breaking rectangular notches in isotropic plates is presented. The results are
      obtained from finite element time domain simulations together with experimental
      measurements. Very good agreement is found between the simulations and the
      measurements. Results are shown for a range of notch widths and depths, including
      the special case of a crack, defined as a zero-width notch. An interference
      phenomenon is identified which explains the periodic nature of the reflection
      coefficient when plotted as a function of notch width. Finally, an analysis using
      the S-parameter approach and both low and high frequency asymptotic analyses
      yields physical explanations of the nature of the reflection behavior from the
      cracks. It is found that the low frequency (quasistatic) approximation may be
      used accurately for cracks up to about a quarter of the plate thickness, provided
      that the quasistatic crack-opening function is chosen such that bending of the
      plate is omitted. At higher frequencies and depths the functions tend towards the
      high frequency (ray theory) predictions but these are never accurate models
      within the nondispersive frequency range of the s0 mode.

PMID- 11833540
TI  - Arthroscopic protocol for treatment of knee extension block after patellar ACL
      reconstruction.
AB  - This study presents a new protocol for arthroscopic approach based on the
      treatment of 36 patients with extension block of the knee as a result of intra
      articular reconstruction of the anterior cruciate ligament (ACL) using the
      patellar tendon. Arthroscopy not only allowed the identification of the active
      mechanical extension block of the knee, but also the passive mechanical block
      that can occur with a functional or loose ligament. This protocol can be useful
      in the treatment of postoperative extension block of the knee as a complication
      of ACL reconstruction.

PMID- 11833542
TI  - Experimental derivation of wall correction factors for ionization chambers used
      in high dose rate 192Ir source calibration.
AB  - At present there are no specific primary standards for 192Ir high dose rate
      sources used in brachytherapy. Traceability to primary standards is guaranteed
      through the method recommended by the AAPM that derives the air kerma calibration
      factor for the 192Ir gamma rays as the average of the air kerma calibration
      factors for x-rays and 137Cs gamma-rays or the Marechal et al. method that uses
      the energy-weighted air kerma calibration factors for 250 kV x rays and 60Co
      gamma rays as the air kerma calibration factor for the 192Ir gamma rays. In order
      to use these methods, it is necessary to use the same buildup cap for all
      energies and the appropriate wall correction factor for each chamber. This work
      describes experimental work used to derive the A(W) for four different ionization
      chambers and different buildup cap materials for the three energies involved in
      the Marechal et al. method. The A(W) for the two most common ionization chambers
      used in hospitals, the Farmer NE 2571 and PTW N30001 is 0.995 and 0.997,
      respectively, for 250 kV x rays, 0.982 and 0.985 for 192Ir gamma rays, and 0.979
      and 0.991 for 60Co gamma rays, all for a PMMA build-up cap of 0.550 gm cm(-2). A
      comparison between the experimental values and Monte Carlo calculations shows an
      agreement better than 0.9%. Availability of the A(W) correction factors for all
      commercial chambers allows users of the in-air calibration jig, provided by the
      manufacturer, to alternatively use the Marechal et al. method. Calibration
      laboratories may also used this method for calibration of a well-type ionization
      chamber with a comparable accuracy to the AAPM method.

PMID- 11833541
TI  - Conformational flexibility of three cytoplasmic segments of the angiotensin II
      AT1A receptor: a circular dichroism and fluorescence spectroscopy study.
AB  - The conformation of three synthetic peptides encompassing the proximal and distal
      half of the third intracellular loop (Ni3 and Ci3) and a portion of the
      cytoplasmic tail (fCT) of the angiotensin II AT1A receptor has been studied using
      circular dischroism and fluorescence spectroscopies. The results show that the
      conformation of the peptides is modulated in various ways by the environmental
      conditions (pH, ionic strength and dielectric constant). Indeed, Ni3 and fCT fold
      into helical structures that possess distinct stability and polarity due to the
      diverse forces involved: mainly polar interactions in the first case and a
      combination of polar and hydrophobic interactions in the second. The presence of
      these various features also produce distinct intermolecular interactions. Ci3,
      instead, exists as an ensemble of partially folded states in equilibrium. Since
      the corresponding regions of the angiotensin II AT1A receptor are known to play
      an important role in the receptor function, due to their ability to undergo
      conformational changes, these data provide some new clues about their different
      conformational plasticity.

PMID- 11833543
TI  - Evaluation of protective shielding thickness for diagnostic radiology rooms:
      theory and computer simulation.
AB  - This work presents the development and evaluation using modern techniques to
      calculate radiation protection barriers in clinical radiographic facilities. Our
      methodology uses realistic primary and scattered spectra. The primary spectra
      were computer simulated using a waveform generalization and a semiempirical model
      (the Tucker-Barnes-Chakraborty model). The scattered spectra were obtained from
      published data. An analytical function was used to produce attenuation curves
      from polychromatic radiation for specified kVp, waveform, and filtration. The
      results of this analytical function are given in ambient dose equivalent units.
      The attenuation curves were obtained by application of Archer's model to computer
      simulation data. The parameters for the best fit to the model using primary and
      secondary radiation data from different radiographic procedures were determined.
      They resulted in an optimized model for shielding calculation for any
      radiographic room. The shielding costs were about 50% lower than those calculated
      using the traditional method based on Report No. 49 of the National Council on
      Radiation Protection and Measurements.

PMID- 11833544
TI  - Hydrophobic interaction chromatography of homo-oligonucleotides on derivatized
      Sepharose CL-6B. Application of the solvophobic theory.
AB  - This work describes the hydrophobic interaction chromatography of homo
      deoxyoligonucleotides polyA, polyT and polyU with sizes up to 30 bases on a
      Sepharose gel derivatized with the 1,4-butanediol diglycidyl ether. The
      oligonucleotides interacted differently with the column according to the
      molecular mass, the hydrophobic character of the individual bases, the secondary
      structure of the molecule and the concentration of ammonium sulphate in the
      eluent. The retention factor, k', was determined from the chromatographic
      profiles at different concentrations of ammonium sulphate. A linear relationship
      between log k' and the concentration of ammonium sulphate in the eluent was found
      for all oligonucleotides at the higher concentrations (> 1.0 M) of ammonium
      sulphate. The slope of these plots, termed the hydrophobic interaction parameter,
      was found to be an increasing function of the number of nucleotides. The same
      plots reveal that polyA molecules with high molecular mass have lower retention
      factors when compared with polyT, an observation that was not expected since the
      hydrophobicity of adenine is higher than that of thymine. This behaviour was due
      to the existence of secondary structures in polyA, which decrease the exposed
      hydrophobic area of the molecule.

PMID- 11833545
TI  - Optimization of azeotropic protein separations in gradient and isocratic ion
      exchange simulated moving bed chromatography.
AB  - The separation of dilute binary mixtures of proteins by salt aided ion-exchange
      simulated moving bed (SMB) chromatography is optimized with respect to
      throughput, desorbent consumption and salt consumption. The optimal flow-rate
      ratios are analytically determined via an adopted "triangle theory". Azeotropic
      phenomena are included in this procedure. The salt concentrations in the feed and
      recycled liquid are subsequently determined by numerical optimization. The
      azeotropic separation of bovine serum albumin and a yeast protein is used to
      illustrate the procedure. Gradient operation of the SMB is generally preferred
      over isocratic operation. A feed of azeotropic salt concentration can only be
      separated in a gradient SMB. Desorbent and salt consumption are always lower in
      gradient than in isocratic SMB chromatography.

PMID- 11833547
TI  - Re: Stroke Therapy Academic Industry Roundtable II (STAIR-II).

PMID- 11833548
TI  - Major ongoing stroke trials.

PMID- 11833549
TI  - Pericarditis presenting and treated as an acute anteroseptal myocardial
      infarction.

PMID- 11833550
TI  - The safety and efficacy of formoterol (Oxis) turbuhaler plus budesonide
      (Pulmicort) turbuhaler in mild to moderate asthma: a comparison with budesonide
      Turbuhaler alone and current non-corticosteroid therapy in Russia.
AB  - Current therapy in Russia for long-term management of asthma is mainly non
      steroidal. This provided the opportunity to compare the efficacy and safety of
      formoterol (Oxis) Turbuhaler plus budesonide (Pulmicort) Turbuhaler with
      budesonide Turbuhaler alone in adults (n=338) with mild to moderate asthma who
      had little previous exposure to inhaled corticosteroids. The 12-week study
      followed a randomised, double-blind, parallel group design and included an open
      control group of patients who were treated with conventional non-corticosteroid
      therapy. Patients treated with formoterol plus budesonide benefited from a
      significantly greater improvement in their pulmonary function and asthma symptoms
      compared with budesonide alone (95% Cl of difference in mean morning peak
      expiratory flow [PEF] 8.7-36.3 l/min, p=0.0015). Non-corticosteroid treatment was
      significantly less effective than formoterol plus budesonide and budesonide alone
      (95% CIs of differences in mean morning PEF were 36.4-63.6 l/min and 14.1-41.1
      l/min, respectively, both p=0.0001). Although the incidence and frequency of
      adverse events was not significantly different between the groups, formoterol
      plus budesonide and budesonide alone were better tolerated than non
      corticosteroid treatment, and there were fewer incidences of asthma
      deterioration. Overall, formoterol Turbuhaler plus budesonide Turbuhaler was the
      safest and most effective treatment.

PMID- 11833551
TI  - Development of a nurse-led chronic pain clinic in UK primary care.
AB  - We describe the development of an innovative, nurse-led chronic pain clinic in
      primary care. Benefit of the structured intervention was seen in terms of overall
      patient pain (as measured by the short form McGill-Melzack pain scale) with no
      overall impact on drug costs. A significant proportion (54%) of patients taking
      non-steroidal anti-inflammatory drugs were deemed to be at risk of gastropathy
      and in need of gastroprotection as defined by the clinic protocol. Areas worthy
      of further study are discussed.

PMID- 11833552
TI  - Referral patterns to a district general hospital gastroenterology outpatient
      clinic: implications for the 'two-week target'.
AB  - We defined the pattern and appropriateness of GPs' new-patient referrals to a
      large district general hospital gastroenterology department, and assessed the
      implications for workload in the context of the recently introduced 'two-week
      target'. Prospective data were collected on all new referrals over a two-month
      period and 426 new appointments were included, from which data were available on
      390. Only six referrals were deemed inappropriate. Sixty-nine patients had a
      functional disorder, and GPs were less likely to diagnose this group at referral
      than the gastroenterologist was after the initial consultation. Nineteen per cent
      of all GP referrals were classified as urgent and 6% of these had a malignancy.
      Fifty per cent of patients with malignancy were not perceived as meriting an
      urgent referral by the GP Gastroenterology outpatient facilities are already
      overstretched and the implementation of the two-week target will add considerable
      strain to the current resources, with little gain in identifying malignancy.

PMID- 11833554
TI  - Seizure recurrence in temporal lobe epilepsy.
AB  - We report on a patient with clinical, electroencephalographic and radiological
      features of temporal lobe epilepsy, whose seizures were initially controlled with
      antiepileptic treatment. Five years after the onset of seizures, he developed
      more frequent and prolonged episodes of confusion, which were misinterpreted as
      secondary to temporal lobe epilepsy. Further investigation revealed the presence
      of hypoglycaemia and the eventual diagnosis of metastatic insulinoma.

PMID- 11833555
TI  - Regenerative medicine: tissue engineering standards come to ASTM.

PMID- 11833556
TI  - The year of the clone?

PMID- 11833553
TI  - A systematic review of the evidence for rapid access chest pain clinics.
AB  - To determine the impact of rapid access chest pain clinics (RACPC) on patient
      management, a systematic search (1966-2000) was performed of electronic
      databases, recent conference abstracts, citations of all identified studies, and
      by contact with other researchers. Studies of any design were included.
      Assessment of eligibility, methodological quality of studies and data abstraction
      was conducted independently by two reviewers. Outcome measures were sought in
      terms of admission rate of patients without acute coronary syndrome detection
      rate of acute coronary syndrome unrecognised by the GP, timing of specialist
      assessment of patients with stable angina and speed and accuracy of detection of
      those with non-cardiac chest pain. Nine relevant studies were found, but all had
      methodological flaws when considered as evaluative studies. All clinics described
      reviewed patients within 24 hours of referral. Only three studies made
      comparisons with control groups, none of which were randomised, and a further
      three provided follow-up data only. Limited data were found for all four outcome
      measures, indicating possible benefits of RACPCs. However, all findings could be
      explained by potential biases in the original studies. In conclusion, the
      evidence base for the introduction of rapid access chest pain clinics is poor.
      The introduction of these clinics should include a randomised prospective
      evaluation of their worth.

PMID- 11833558
TI  - Assisted suicide: the tip of the iceberg.

PMID- 11833559
TI  - Institutional review boards and financial conflict of interest.

PMID- 11833560
TI  - Veterans Affairs is first to require IRB accreditation.

PMID- 11833561
TI  - Task force ready on financial conflict of interest in research.

PMID- 11833562
TI  - Guidance on financial disclosure requirements.

PMID- 11833563
TI  - Subject's representative says at first that he will not sue researchers.

PMID- 11833564
TI  - Institutional review boards should not have primary conflict of interest duty.

PMID- 11833565
TI  - Institutional review boards and the new privacy rule.

PMID- 11833566
TI  - More protections when children are subjects.

PMID- 11833567
TI  - IRBs and Humanitarian Device Exemptions (HDEs).

PMID- 11833568
TI  - Federal agency says researcher misled colleagues and institutional
      administrators.

PMID- 11833569
TI  - One unified policy recommended for all human research studies.

PMID- 11833570
TI  - First human research accreditation in place.

PMID- 11833571
TI  - No waiver of parental consent for research.

PMID- 11833573
TI  - Fellow scientists begin to get suspicious about data.

PMID- 11833572
TI  - Financial disclosures by investigators.

PMID- 11833574
TI  - Proposed federal office includes ethics oversight for research with children.

PMID- 11833575
TI  - Global arguments for the safety of engineered organisms.

PMID- 11833576
TI  - Virtue ethics and psychology.

PMID- 11833577
TI  - The perception of ethical dilemmas in clinical practice.
AB  - The empirical diagnosis presented in this paper is based on interviews with nurse
      practitioners and physicians designed to elicit their perceptions on the nature
      and role of ethical dilemmas in clinical practice. Having selected five of these
      perceptions or views which were common and significant, the philosophical therapy
      offered consists in, first, a general discussion of ethical dilemmas and, second,
      a critical analysis of each of the five views with the aim of pointing out
      confusions and errors, the recognition of which can be of applied and practical
      help in the clinical setting.

PMID- 11833578
TI  - Exploitation, autonomy, and the case for organ sales.
AB  - A recent argument in favor of a free market in human organs claims that such a
      market enhances personal autonomy. I argue here that such a market would, on the
      contrary, actually compromise the autonomy of those most likely to sell their
      organs, namely, the least well off members of society. A Marxian-inspired notion
      of exploitation is deployed to show how, and in what sense, this is the case.

PMID- 11833579
TI  - Bioethics in a liberal society--political, not moral.
AB  - This paper argues for the importance of the political context of a society for
      bioethics. In particular, I argue that in a liberal constitutional society, such
      as the one we find ourselves in, no particular moral perspective is granted a
      privileged position. Rather, individuals are allowed to live their lives
      according to values they adopt for themselves, and the rights granted to protect
      this ability "trump" social consensus, and place boundaries on the social
      application of personal moral beliefs and values.

PMID- 11833580
TI  - Lying and deceiving--moral choice in public and private life.
AB  - Suppose that there are good or morally defensible reasons for not responding
      truthfully to a question or request for information. Is a lie or a deception
      better as a means to avoid telling the truth? There are many situations in public
      and private life in which the answer to this question would serve as a useful
      moral guide, for instance, clinical situations involving dying patients,
      educational situations, involving young children and personal situations
      involving close friends. Intuitively, we feel that there is a moral asymmetry in
      favor of deceiving over lying. However, doubts have been cast on such intuition.
      The aim of this paper is to bolster this intuition. It will be argued that the
      claim of moral asymmetry in favor of deception can be supported on a
      consideration of the different degrees of expectation involved in communicative
      ethics. Two other objections to the claim of asymmetry will also be considered.

PMID- 11833581
TI  - Ethical considerations and training recommendations for philosophical counseling.
AB  - Philosophical counseling is a diverse and burgeoning type of mental health
      service delivery. Despite competing approaches to theory and practice, the field
      has largely strayed from an ethical critique of its methodology and counselor
      training requirements. This article outlines several ethical considerations and
      training recommendations that are proposed to bolster the quality and
      effectiveness of philosophical practice. As philosophical counseling gains
      increasing recognition in North America, recently established national
      organizations in philosophical practice may profit from revisiting their interim
      codes for professional conduct. Proposed training suggestions for counselor
      preparation my further assist institutions and board-regulated agencies in
      establishing competent and acceptable standards of client care.

PMID- 11833582
TI  - Ethical androcentrism and maternal substance addiction.
AB  - In this paper, I argue that bioethics suffers from a masculinist approach--what I
      call "ethical androcentrism." Despite the genesis of other legitimate approaches
      to ethics (such as feminist, narrative, and communicative ethics), this
      masculinist tradition persists. The first part of my paper concerns the problem
      of ethical androcentrism, and how it is manifest in our typical ways of "doing"
      bioethics (as teachers, ethicists, policymakers, and medical practitioners).
      After arguing that bioethics suffers from a masculinist ethic, I consider the
      case of maternal substance addiction to show how this ethic negatively affects
      the treatment of pregnant addicts. I argue that by treatment maternal substance
      addiction from an androcentric approach, we fail to serve both pregnant addicts
      and their fetuses; furthermore, we misrepresent the intentional state of pregnant
      substance addicts and label them "prenatal abusers." If maternal substance
      addiction is to be ethically addressed--and if pregnant substance addicts are to
      be effectively treated--we cannot tacitly accept an androcentric ethic.

PMID- 11833583
TI  - Codes of medical ethics and the exportation of less-than-standard care.
AB  - Recently a number of AIDS/AZT research studies, carried out by U.S. universities,
      have come under intense ethical scrutiny. In these studies, control groups of HIV
      positive pregnant women were being given a placebo rather than AZT. Such research
      protocols would be illegal if practiced in the U.S. I examine a number of
      lamentable ethical lapses in the studies, and conclude that at least some of
      these ethical problems are traceable to a troubling contradiction between
      differing international codes of ethics. In a word, some international codes
      mandate that all research subjects (including control groups) receive the best
      standard of care available in the country sponsoring the research, while others
      suggest that providing only a "local" standard of care is ethically appropriate.
      I argue that these two ethical mandates cannot both be satisfied, and that host
      country populations will remain subject to exploitation unless this contradiction
      is resolved.

PMID- 11833584
TI  - Nietzsche and the dilemma of suffering.
AB  - In this paper, we attempt to view a long-held assumption in nursing as mistaken.
      That is, that patient suffering is something to be overcome. Utilizing
      Nietzsche's statements on Amor Fati, we carefully examine the cultural
      assumptions behind our denigration of suffering, look at specific nursing
      examples of this situation, and attempt the beginnings of a discourse on what it
      would take for nurses to overcome their own predetermined views of suffering in
      order to better help their patients "own" their own suffering.

PMID- 11833585
TI  - On human improvement.
AB  - The claim that human cognitive abilities can be markedly improved by near-future
      biophysical means is examined as to its clarity, desirability, and feasibility.
      Generally, this is a study of the "space of reasons" of such a claim. Comparison
      is offered to claims of the feasibility of significant moral improvement of
      individuals. While this study is more exploratory than conclusive, the result is
      drawn that the possibility of such improvement merits serious consideration,
      given such improvement's far-reaching implications.

PMID- 11833586
TI  - Paediatrics: the individuals and external influences involved in forming this
      special branch of medicine, from Hippocrates to the present day.

PMID- 11833587
TI  - The Russells of Edinburgh: a medical dynasty.

PMID- 11833588
TI  - The life, work and gender of Dr James Barry MD (1795-1865).

PMID- 11833589
TI  - Matthew Baillie Gairdner, The Royal Medical Society and the problem of the second
      heart sound.
AB  - In 1830, Matthew Baille Gairdner (1808-88) was the first to propose that the
      second heart sound was produced by the closure of the semilunar valves. He
      proposed this theory, while a student at Edinburgh University, in an oral
      presentation to the Royal Medical Society (RMS). Gairdner (Figure 1) has been
      largely ignored by both nineteenth and twentieth century historians of
      cardiology. This paper presents an account of his life, his discovery and the
      scientific controversy to which he contributed, and argues that an appreciation
      of his work and that of his student colleagues should cause us to re-evaluate the
      significance of the RMS as a research forum in the early nineteenth century.
      Suggestions are made as to why his contribution to our understanding of the heart
      sounds has been neglected.

PMID- 11833590
TI  - Oncology nurses, pharmacists, and oncologists sought to develop standards for
      chemotherapy gloves.

PMID- 11833591
TI  - ASTM lights the way for tissue engineered medical products standards: jump start
      for combination medical products that restore biological function of human
      tissues.
AB  - Everybody hopes for better health and restoration of impaired bodily function,
      and now that hope is illuminated by the promise of powerful biological tools that
      make human cells grow and replace human tissue. ASTM Committee F04 on Medical and
      Surgical Materials and Devices is taking the lead by defining some of those tools
      as standards that can be used for the development, production, testing, and
      regulatory approval of medical products.

PMID- 11833592
TI  - Medical devices, health care, and consensus standards.
AB  - ASTM Committee F04 on Medical and Surgical Materials and Devices has been
      creating standards for this field since 1962. Dr. Jack Lemons provides a quick
      overview of the past, present, and future of this committee.

PMID- 11833593
TI  - There's a fungus among us.

PMID- 11833594
TI  - Animal therapy over the ages: 6. botanical medicine in the twentieth century.

PMID- 11833595
TI  - Anecdotal history: a forgotten chapter in the history of veterinary medicine.

PMID- 11833596
TI  - Reading and writing veterinary history.

PMID- 11833597
TI  - Rinderpest: one virus's impact on veterinary history.

PMID- 11833598
TI  - Nineteenth-century veterinary medicine as an urban profession.

PMID- 11833600
TI  - Coming full circle: a history of the 168th medical detachment (VS).

PMID- 11833599
TI  - Zoonoses 1879-1983: an update of James Law's report on diseases of animals.

PMID- 11833601
TI  - Animal therapy over the ages: 4. early botanical medicine.

PMID- 11833602
TI  - Veterinarians in zoo medicine: the evolution of a career.

PMID- 11833603
TI  - Property, progeny, body part: assisted reproduction and the transfer of wealth.

PMID- 11833604
TI  - Rethinking a women's health care agenda.
AB  - The baby boom population has entered middle age. In addition many people,
      especially women, are living into old age. These are large population cohorts
      that are politically engaged. Also there is money to be made by commercial
      stakeholders in responding to the health risks of these women. The definition of
      women's health care needs has changed in the past decade. Traditionally the
      defining characteristics of women's health policy were reproduction, childbearing
      and a woman's role as a sexual partner. Today it also includes the way that
      different diseases affect women and the best way to reach women at risk for a
      wide range of conditions, e.g., heart disease, cancer and depression.

PMID- 11833605
TI  - Cytoarchitectural and axonal maturation in human auditory cortex.
AB  - This study followed the maturation of human auditory cortex from the beginning of
      the second trimester of gestation to young adulthood. Histological and
      immunohistochemical techniques were used to trace the development of a laminar
      cytoarchitecture and an adult pattern of axonal neurofilament expression. From
      the 16th fetal week to the 4th postnatal month, the cortex progresses from a
      marginal layer and an undifferentiated cortical plate to incipient lamination.
      Between the 22nd fetal week and the 4th postnatal month, a two-tiered band of
      neurofilament-immunoreactive axons develops in layer I, but subsequent to the 4th
      month, the number of immunopositive axons in this layer is greatly reduced.
      Between the middle of the first year of life and age 3 years, the laminar pattern
      of cytoarchitecture becomes fully mature and a network of immunostained axons
      develops in layers VI, V, IV, and IlIc. This axonal plexus in the deep cortical
      layers continues to increase in density until age 5. Beginning at 5 years of age,
      a network of neurofilament-positive axons develops in the superficial layers
      IIIb, IIIa, and II, and by 11-12 years of age, overall axonal density is
      equivalent to that seen in young adulthood. This extended time span of axonal
      maturation has implications for the emergence of auditory cortical function.

PMID- 11833606
TI  - Consequences of hypothyroidism on auditory system function in Tshr mutant (hyt)
      mice.
AB  - The otological consequences of hypothyroidism and the outcome of thyroxin (T4)
      administration during the developmental period preceding the onset of hearing
      were examined in mice that express a point mutation in the gene encoding the
      thyrotropin receptor (Tshr), the so-called hyt mouse. Progeny of sires homozygous
      for the trait and heterozygous dams were injected with T4 or saline placebo from
      birth through the tenth postnatal day and auditory-evoked brainstem responses
      (ABRs) to acoustic clicks and tone bursts were recorded from young adults. Mutant
      (hyt/hyt) mice exhibited a distinctive pattern of sensory pathology that was
      characterized by their insensitivity to sound, prolonged response latencies,
      reduced peak amplitudes, and steep latency-intensity curves relative to the
      phenotypically normal, euthyroid, +/hyt littermates. Following thyroxin
      treatment, hyt/hyt mice responded to acoustic stimuli more frequently, were more
      sensitive to tone bursts throughout their audiometric range, and exhibited
      decreased latencies and increased amplitudes when compared with placebo-treated
      homozygous mutants. Although thresholds to acoustic stimuli were improved
      relative to the untreated group, T4-treated homozygotes were less sensitive than
      normal, euthyroid individuals. In addition, energy consumption by auditory
      brainstem nuclei, measured by 2-deoxyglucose (2-DG) uptake, was significantly
      lower in hyt/hyt mice compared with heterozygotes, and T4 treatment increased the
      level of 2-DG utilization. Moreover, mean ages for eye-opening and pinna-raising
      were delayed in animals that were homozygous for the hyt allele. When T4 was
      administered to hyt/hyt animals, pinna-raising occurred earlier than in untreated
      animals. A subset of homozygotes exhibited circling behavior, indicative of
      vestibular and/or motor dysfunction, even though all individuals assumed a normal
      righting reflex. These findings, including recruitment-like behavior and the
      restoration of response magnitude at high levels but not low, suggest that the
      cochlear amplifier is the primary locus of an enduring otological defect
      associated with hypothyroidism in the Tshr mouse.

PMID- 11833607
TI  - Development of auditory brainstem responses (ABRs) in Tshr mutant mice derived
      from euthyroid and hypothyroid dams.
AB  - Developmental changes in auditory brainstem responses (ABRs) to clicks and tone
      bursts were studied in genetically hypothyroid Tshr mutant mice that were
      homozygous for the hypothyroid trait (hyt/hyt), as well as in euthyroid
      individuals that were heterozygous for the trait (+/hyt). The developmental role
      of maternal thyroid hormones was determined by comparing homozygotes that were
      offspring of euthyroid (hyt/hyt(c)) or hypothyroid (hyt/hyt(h)) dams; all
      heterozygotes were born to euthyroid dams (+/hyt(e)). Clear responses to high
      level stimuli were recorded from heterozygotes on postnatal day 12 (P12) for most
      stimulus conditions, and thresholds, response amplitudes, interpeak intervals,
      and latencies developed normally, achieving nearly adult properties by P21. Most
      hyt/hyt(h) animals were unresponsive to acoustic stimulation throughout the
      period of study. Grossly immature responses to high-level stimuli were observed
      in many hyt/hyt(e) pups on P15; however, clear, low-amplitude responses were not
      routinely observed until P21. Thresholds improved with age in +/hyt(e) and
      hyt/hyt(e) individuals, and latency-level curves were relatively steep in young
      animals and developed normally in +/hyt(e) mice with the most significant changes
      occurring between P15 and P21. In general, hyt/hyt(e) mice exhibited prolonged
      latencies, interpeak intervals, and central conduction times throughout the age
      range studied, and slopes of latency-level curves remained abnormally steep
      through P28. Response amplitudes were generally larger in heterozygotes than in
      hyt/hyt(e) mice, regardless of level. Replacement of thyroxin during the first 10
      postnatal days in hyt/hyt(h) pups had little to no effect on the development of
      auditory function, although more animals from this group were responsive at very
      high stimulation levels. We conclude that auditory function is impaired in
      hypothyroid Tshr animals throughout development and that impairment is profound
      when individuals are not exposed to maternal thyroid hormone, i.e., a clear
      thyroxin-dependent critical prenatal period exists in the Tshr mutant mouse.

PMID- 11833608
TI  - Prevention of auditory dysfunction in hypothyroid Tshr mutant mice by thyroxin
      treatment during development.
AB  - Based on previous work, it is clear that genetically hypothyroid Tshr(hyt) mutant
      mice are congenitally deaf [O'Malley et al. (1995) Hear. Res. 88: 181-189,
      Sprinkle et al. 2001b, J. Assoc. Res. Otolaryngol. DOI: 10.1007/s101620010077].
      However, the extent to which auditory development is dependent on the
      availability of thyroxin (T4) during specific developmental stages is unknown.
      The aim of this study was to determine the relative importance of prenatal and
      postnatal thyroxin on the ontogeny of hearing in the hyt mouse. Experimental
      hypothyroid subjects were offspring of hyt/hyt breeders implanted with T4 or
      placebo controlled-release pellets 14 days prior to mating. Pups received T4 or
      saline placebo injections from birth through postnatal day 14 (P14) or the time
      of testing on P28. In the absence of exogenous T4 replacement, very high stimulus
      levels (>80 dB SPL) were required to elicit responses. Remarkably, T4 treatment
      confined to the postnatal period failed to significantly improve auditory
      function relative to untreated animals, while response thresholds, latencies, and
      amplitudes of mice born to dams that received T4 during pregnancy were
      significantly improved relative to both of the untreated groups. Response
      thresholds were improved somewhat when maternal T4 replacement was followed by
      treatment during the first 14 days of life, and animals treated throughout
      prenatal and postnatal life were comparable to those of age-matched euthyroid
      individuals. Findings from this study show that treatment of hyt/hyt mice with
      exogenous T4 significantly attenuates hypothyroid-induced otopathology in a
      develop-mental-stage-dependent manner. In addition, we demonstrate that postnatal
      development is critically dependent on prenatal exposure to thyroxin and that the
      critical window of T4 dependence extends throughout development.

PMID- 11833609
TI  - Positional analysis of guinea pig inner hair cell membrane conductances:
      implications for regulation of the membrane filter.
AB  - In mammals, sound transduction by inner hair cells (IHC) generates a receptor
      potential whose amplitude and phase drive auditory nerve firing. The membrane
      filter properties that define the input-output function of IHC are derived from
      membrane conductance and capacitance. These elements of the membrane filter were
      quantified using whole-cell voltage clamp of IHC from the four turns of the
      guinea pig cochlea. IHC membrane properties were remarkably constant along the
      cochlea, in contrast with all other auditory hair cell systems, and suggests that
      extrinsic processes such as the active filter provided by the outer hair cells
      are matched to a constant transfer function of the IHC. Two outwardly rectifying
      K+ currents contribute to the IHC membrane conductance. These combined currents
      activate at approximately -55 mV. IHC mean input resistance was 140 M ohm and
      capacitance was 10.0 pF, generating a membrane time constant of 1.4 ms or a
      corner frequency of approximately 115 Hz, which is consistent with reported low
      frequency roll-off of the IHC AC receptor potential in vivo. Approximately 40% of
      the 313-1 nS total K+ conductance about 0 mV was attributed to charybdotoxin
      sensitive K(Ca) channels (also sensitive to cell dialysis with the Ca2+ chelator
      BAPTA or removal of extracellular Ca2+). The only known ligand-activated
      conductance in mature IHC, the P2X receptor conductance, averaged 31 nS
      (activated by 400 microM ATP; about -75 mV) irrespective of cell origin. Thus,
      regulation of intracellular Ca2+ and activation of P2X receptors by extracellular
      ATP provide capacity for local dynamic fine-tuning of the IHC membrane filter.

PMID- 11833610
TI  - Ras/MEK but not p38 signaling mediates NT-3-induced neurite extension from spiral
      ganglion neurons.
AB  - Neurotrophin (NT)-3 is expressed in the neuronal target tissue of the developing
      rat cochlea and has been shown to promote the survival and neurite outgrowth of
      spiral ganglion (SG) neurons, suggesting a role for this protein during the
      innervation of the organ of Corti. In other neurons, NT-3 can mediate
      neuritogenesis and survival via a number of intracellular signal pathways. To
      date, the intracellular transduction pathways involved in the mediation of NT-3
      effects have not been investigated in SG neurons. To determine whether the
      activities of NT-3 on SG neurons are dependent on the activation of mitogen
      activated protein kinase kinases (MEK)/extracellular-signal-regulated kinases
      (ERK), Ras, and/or p38, SG explants from postnatal-day 4 rats were cultured with
      NT-3 and increasing concentrations of the MEK inhibitor U0126, the Ras farnesyl
      transferase inhibitor (FTI)-277, and the p38 inhibitor SB203580. After fixation
      and immunocytochemical labeling, neurite growth was evaluated. A dose-dependent
      decrease of the effects of NT-3 on length and number of processes was observed in
      the U0126- and FTI-277-treated SG neurons. In contrast, SB203580 had no
      significant effect on NT-3-mediated stimulation of neurite growth, in terms of
      either number or length. The results suggest that NT-3 effects on SG neurons are
      mediated primarily by the Ras/MEK/ERK signaling pathway.

PMID- 11833611
TI  - Gap duration discrimination in listeners with cochlear hearing loss: effects of
      gap and marker duration, frequency separation, and mode of presentation.
AB  - This study examined the effects of cochlear hearing loss on gap duration
      discrimination (GDD), with particular interest in whether cochlear hearing loss
      results in increased difficulty for across-channel temporal judgments. The
      hypothesis being tested was that listeners with cochlear loss would perform as
      well as normal-hearing listeners for all within-channel conditions but would
      exhibit relatively greater performance deficits in the across-channel conditions.
      A subsidiary aim was to determine whether, in normal-hearing listeners, the
      across-channel effects previously observed for minimal-duration standard gaps
      also existed for relatively long standard gaps. Two experiments were undertaken,
      one dealing with monaural conditions and one dealing with dichotic conditions.
      The monaural results indicated that across-frequency GDD was poorer than
      isofrequency GDD, even for the longer gap durations of 35 and 250 ms examined
      here. However, the results showed no effect of hearing loss on GDD. Rather, GDD
      appeared to be sensitive to listener age, with younger listeners showing better
      performance in both within-channel and across-channel conditions. In addition,
      both within-channel and across-channel performance was sensitive to the duration
      of the leading gap marker. Finally, the pattern of dichotic "across-ear"
      performance was similar, but not equivalent, to that of monaural across-frequency
      performance.

PMID- 11833613
TI  - Psychophysical estimates of cochlear phase response: masking by harmonic
      complexes.
AB  - Harmonic complexes with identical component frequencies and amplitudes but
      different phase spectra may be differentially effective as maskers. Such harmonic
      waveforms, constructed with positive or negative Schroeder phases, have similar
      envelopes and identical long-term power spectra, but the positive Schroeder-phase
      waveform is typically a less effective masker than the negative Schroeder-phase
      waveform. These masking differences have been attributed to an interaction
      between the masker phase spectrum and the phase characteristic of the basilar
      membrane. To explore this relationship, the gradient of stimulus phase change
      across masker bandwidth was varied by systematically altering the Schroeder-phase
      algorithm. Observers detected a signal tone added in-phase to a single component
      of a masker whose frequencies ranged from 200 to 5000 Hz, with a fundamental
      frequency of 100 Hz. For signal frequencies of 1000-4000 Hz, differences in
      masking across the harmonic complexes could be as large as 5-10 dB for phase
      gradients changing by only 10%. The phase gradient that resulted in a minimum
      amount of masking varied with signal frequency, with low frequencies masked least
      effectively by stimuli with rapidly changing component phases and high
      frequencies masked by stimuli with more shallow phase gradients. A gammachirp
      filter was implemented to model these results, predicting the qualitative changes
      in curvature of the phase-byfrequency function estimated from the empirical data:
      In some cases, small modifications to the gammachirp filter produced better
      quantitative predictions of curvature changes across frequency, but this filter,
      as implemented here, was unable to accurately represent all the data.

PMID- 11833612
TI  - ATP and nitric oxide modulate intracellular calcium in isolated pillar cells of
      the guinea pig cochlea.
AB  - Supporting cells in the mammalian cochlea have recently received attention as
      potential targets of neurotransmitters, neuromodulators, and neurohumoral agents.
      Calcium homeostasis in Deiters' and Hensen's cells, for example, is regulated by
      ATP and nitric oxide. We studied the intracellular calcium concentration [Ca2+]i
      in isolated pillar cells of the guinea pig cochlea in response to extracellular
      ATP and nitric oxide using the fluorescent indicator fluo-3. [Ca2+]i increased
      rapidly and significantly throughout the pillar cell in response to a bolus of
      ATP or 2-methylthio ATP while alpha,beta-methylene ATP was ineffective. The
      response to ATP was inhibited by suramin and Cibacron Blue but not by pyridoxal
      phosphate 6-azophenyl-2',4'-disulfonic acid. This pharmacological profile is
      consistent with a [Ca2+]i increase largely mediated by P2Y receptors. In Ca2+
      free medium supplemented with EGTA, the response to extracellularATP was reduced
      by 33%, suggesting a contribution of calcium influx to the overall effect. The
      ATP-induced increase of [Ca2+] was attenuated by NO donors (sodium nitroprusside
      or diethylamine NONOate), and this attenuation was reversed by KT5823, an
      antagonist to protein kinase G. The results indicate the involvement of
      purinergic mechanisms and the nitric oxide/cyclic GMP/protein kinase G pathway in
      the regulation of [Ca2+]i in cochlear pillar cells.

PMID- 11833614
TI  - Flavonol glycosides from Elaeagnus lanceollata (Elaeagnaceae).
AB  - Two new flavonol glycosides were isolated together with two known glycosides and
      an ester from the leaves of E. lanceollata Warb. Their structures were
      characterized by spectroscopic methods.

PMID- 11833615
TI  - A new glycoside, 3-O-demethylcolchicine-3-O-alpha-d-glucopyranoside, from
      Gloriosa superba seeds.
AB  - A new colchicine glycoside, 3-O-demethylcolchicine-3-O-alpha-D-glucopyranoside,
      has been isolated from Gloriosa superba seeds. The assigned structure has been
      corroborated by spectroscopic data and enzymatic hydrolysis.

PMID- 11833616
TI  - Short synthesis of novel 9,11-secosterols.
AB  - Starting from ergosterol two novel 9,11-secosterols with modified side chains
      (1a) and (1c) were synthesized via eight main transformations.

PMID- 11833617
TI  - Enhanced podophyllotoxin production from Agrobacterium rhizogenes transformed
      cultures of Podophyllum hexandrum.
AB  - Podophyllotoxin, a potent chemotherapeutic agent is obtained from Podophyllum
      hexandrum Royle. Embryos of P. hexandrum were transformed using different strains
      of Agrobacterium rhizogenes viz. A4, 15834, K599. Transformed nature of the calli
      was ascertained and the cultures were further maintained as individual clones.
      HPLG analysis of transformed cultures depicted a three-fold increase in
      podophyllotoxin content in comparison to controls.

PMID- 11833618
TI  - N2,N2,7-trimethylguanine, a new trimethylated guanine natural product from the
      New Zealand ascidian, Lissoclinum notti.
AB  - From the New Zealand ascidian, Lissoclinum notti a new natural product, N2,N2,7
      trimethylguanine (1) has been isolated. The structure of 1 was elucidated by
      analysis of spectroscopic data.

PMID- 11833619
TI  - Cytotoxic hydroxyanthracenones from fruits of Karwinskia parvifolia.
AB  - Peroxisomicines A1 (1) and A2 (2) are cytotoxic hydroxyanthracenones isolated
      from the fruits of Karwinskia parvifolia. Peroxisomicine A1 exhibits selective
      cytotoxicity against several tumor cell lines. In the present investigation three
      minor constituents were obtained from the same fruit extracts: peroxisomicine A3
      (3) and isoperoxisomicines A1 (4) and A2 (5). Compounds 3 and 5 are novel and
      their structures were determined by spectroscopic methods and molecular modeling.
      Compounds 1-5 were significantly cytotoxic against hepatoma cell lines.

PMID- 11833620
TI  - Cycloartanes, protolimonoids, a pregnane and a new ergostane from Trichilia
      reticulata.
AB  - The new ergostane steroid ergosta-5,24(24')-diene-3beta,4beta,22R-triol (1), a
      pregnane, (E)-volkendusin, characterised as the diacetate (3), cycloartanes 4-6
      and protolimonoids 7-9 were obtained from the leaves and twigs of Trichilia
      reticulata.

PMID- 11833621
TI  - Bowdenol, a new 2,3-dihydrobenzofuran constituent from Bowdichia virgilioides.
AB  - From the stem bark of Bowdichia virgilioides, lupeol, lupeol acetate, sitosterol,
      stigmasterol and methyl-3-[2-(1-hydroxymethylvinyl)-2,3-dihydrobenzo[b]furan-5
      yl]-(E)-2-propenoate have been isolated. The latter is a new compound and it has
      been named as bowdenol. Their structures were elucidated with the aid of
      spectroscopic techniques, mostly 1 and 2D NMR. The biogenetic pathway for
      bowdenol has been suggested.

PMID- 11833622
TI  - First isolation of geranyl disaccharides from ginger and their relations to aroma
      formation.
AB  - Three geraniol glycosides were isolated from immature fresh ginger rhizomes
      (Zingiber officinale Roscoe). Their structures were identified as geranyl 6-O
      alpha-L-arabinopyranosyl-beta-D-glucopyranoside (1) geranyl 6-O-beta-D
      apiofuranosyl-beta-D-glucopyranoside (2) and geranyl 6-O-beta-D-xylopyranosyl
      beta-D-glucopyranoside (3) by spectrometric analyses. After incubating each
      glycoside with a crude enzyme solution prepared from ginger, geraniol was
      liberated in all of those fractions. This result indicates that the glycosides
      are related to the formation of geraniol-related compounds in ginger aroma.

PMID- 11833624
TI  - Characterization of a new decahydropyridoquinoline from Indigofera longeracemosa
      Boiv. ex Baill. (Fabaceae).
AB  - Repeated silica gel chromatography of the dichloromethane extract of air-dried
      stems of Indigofera longeracemosa followed by reverse-phase HPLC separation
      yielded a new decahydropyridoquinoline, rel-(3S, 5R, 6S, SR, 8aR, 12aR)-8-acetoxy
      6-butyl-3-isothiocyanatodecahydropyrido (2,1) quinoline.

PMID- 11833623
TI  - New antifeedant triterpene glycosides from the Caribbean sponge Erylus formosus.
AB  - Two groups of antifeedant triterpene glycosides were identified from the
      Caribbean sponge Erylus formosus. The structure of formoside B, a novel N-acetyl
      amino derivative of the known penasterol tetrasaccharide formoside, was
      elucidated using NMR and mass spectral data. Four triterpene hexasaccharides and
      two triterpene trisaccharides, characterized by a 31-carbon aglycone, proved
      difficult to isolate and therefore only the structure of their aglycone was
      determined. Gas chromatographic analysis of derivatized saccharides from these
      mixtures established the carbohydrate content of these compounds. All of the
      triterpene glycosides isolated contributed to the chemical defenses of this
      sponge, although with differing activities.

PMID- 11833625
TI  - Reliability of cough effort intensity assessment by nurses.
AB  - This study examines the dependability of naive nursing assessments of cough
      effort intensity (CEI) in unstable, but realistic, clinical situations. Sixty-two
      medical and surgical patients were recruited while on mechanical ventilation and
      studied on 3 consecutive days. Each day, three nurses measured two CEI ratings 3
      minutes apart. Using a generalizability theory approach, the researchers
      estimated multiple sources of error in the measurement of CEI. Patient and day of
      measurement represented systematic variance, planned to increase variability in
      CEI. Time of assessment and nurse rater represented random sources of error. The
      design accounted for all sources of measurement error in the model. Variability
      in CEI was accounted for by individual patient differences and raters nested
      within patient day. The dependability coefficient was .39. Thus, the
      investigators concluded that naive nurse assessments of CEI are undependable in
      clinical situations.

PMID- 11833627
TI  - Use of non-human biobehavioral models in critical care nursing research.
AB  - The complexity of critical care settings and diversity among vulnerable patient
      populations often make clinical research study outcomes difficult to evaluate.
      When interventions are tested, outcomes or improvements in condition often can be
      questioned on the basis of variations in the patient's constitutional, genetic,
      or disease state. Study of mechanisms underlying physiologic problems in the
      seriously ill also are complicated by effects of drugs, preexisting cellular
      damage, and behavioral influences. Animal models are used increasingly in nursing
      science to study clinical problems and care approaches when there is need to
      ensure experimental control and provide consistency across subjects. The
      competent clinical investigator who decides to choose this option is advised to
      seek training in animal care, work with skilled colleagues in the basic sciences,
      and use excellent consultants. Several considerations arise when choosing a non
      human alternative for biobehavioral research. First, there must be a compelling
      reason to choose this model, not simply for convenience or novelty. Second, the
      investigation should be humane, well planned, and well supported. Animal studies
      are not necessarily more economical than those involving humans, and they require
      serious ethical and scientific consideration to justify their use. When these
      conditions are met, the use of non-human models often can clarify a biobehavioral
      mechanism or biophysical response that will contribute significantly to nursing
      science.

PMID- 11833626
TI  - Desaturation events in neonates during mechanical ventilation.
AB  - This study examines the accuracy of oxygen saturation measured by Nellcor N200
      pulse oximetry (SpO2) compared with arterial oxygen saturation (SaO2) measured
      through a three-wavelength fiberoptic umbilical catheter in 10 neonates who
      needed mechanical ventilation. Real-time SaO2 was validated with a reference
      method every 4 hours. Oxygen saturation readings (SaO2 and SpO2), along with
      pulse rate and pulsation, were recorded continuously every second through a
      computer. Concurrent care events and neonatal responses were recorded. Data were
      completed on 10 neonates who had an umbilical arterial catheter. Desaturation
      events (<90%) as measured by both SaO2 and SpO2 were described and compared. A
      total of 959 desaturation events occurred during an average of 51 hours of
      monitoring per subject. Of these events, 63% were associated with frozen SPO2
      readings, and 18% of frozen readings occurred when SaO2 was <90%. Bias for SpO2
      compared with SaO2 was +5.03%, with 5.6% of the readings outside the range of two
      standard deviations. However, 67% of the readings exceeded the 4% difference
      criterion between measurements. Future studies need to examine the desaturation
      events in relation to oxygenation status as measured by different methods.

PMID- 11833628
TI  - Physiologic variability during transition to extrauterine life.
AB  - The first 24 hours of life can be the most precarious in a person's lifespan.
      Physical changes occur so quickly during the transformation from fetus to neonate
      that any deviations from the expected need to be identified and acted on
      immediately to assist the baby toward successful adaptation to extrauterine life.
      Newborns respond to physiologic stress by becoming less responsive, often giving
      few cues that a problem is arising. Transition and physiologic stability have
      traditionally been measured in the time domain. However, heart beat or
      respiratory rate per minute are gross measures that do not reliably alert the
      health care provider to subtle signs of stress. Physiologic variability is mainly
      due to the interaction of the sympathetic and parasympathetic nervous systems.
      Patterns in the variability may be used as indexing variables for the assessment
      of neurophysiologic status. Linear and non-linear analysis of the variability
      promises to provide a sensitive, noninvasive measure for the identification of
      neurophysiologic stress that can better inform the health care provider of the
      fetal and neonatal response to stress.

PMID- 11833629
TI  - Effect of head positioning on intracranial blood flow velocities in acute
      ischemic stroke: a pilot study.
AB  - Current nursing practice for the care of patients with ischemic stroke advocates
      routine elevation of the head of the bed (HOB) to 30 degrees. Evidence supporting
      this practice is lacking, and it may reflect inappropriate generalization of
      findings from studies conducted primarily on traumatic brain injury patients with
      associated increased intracranial pressure to the ischemic stroke population. We
      used a repeated measures design to conduct a pilot study of the effect of three
      HOB positions on middle cerebral artery mean flow velocities (MCA-MFV) in
      patients with acute ischemic stroke. Transcranial Doppler (TCD) sonography was
      used to measure MCA-MFV. Eleven patients were enrolled in the study; the mean age
      of the sample was 60 years, and the mean National Institutes of Health Stroke
      Scale score was 8.7. On average, a 9.2% increase in MCA-MFV was measured when the
      HOB was lowered to 15 degrees from the 30 degrees elevation standard (p = .02);
      MCA-MFV increased on average by 3.9% when the HOB was again lowered from the 15
      degrees position to the 0 degrees (flat) position (p = not significant). Mean
      arterial pressure, heart rate, and pulse pressure remained stable without
      significant change throughout the positioning intervention and measurement
      period. The overall increase in MCA-MFV achieved from lowering the HOB position
      from 30 degrees to a flat position was 13.1% (p = .054). Our findings from this
      small sample suggest that patients with acute ischemic stroke may benefit from
      lower HOB positions, in particular flat positioning, to promote an increase in
      flow to ischemic brain tissue that may ultimately reduce brain infarct volume.

PMID- 11833630
TI  - Special feature: exploring the benefits and myths of enteral feeding in the
      critically ill.
AB  - Patients in the intensive care unit setting have been nutritionally deprived for
      various reasons. Many patients who are critically ill cannot absorb nourishment
      by traditional routes. Enteral feeding should be considered for all patients who
      cannot meet caloric needs. There are many benefits to enteral feeding such as
      decreased infection, rapid wound healing, and decreased length of stay and
      mortality. Many critical care nurses subscribe to myths for not feeding their
      patients. The myths for not feeding critically ill patients involve gut motility,
      feeding residuals, and patient positioning. There is significant evidence both to
      support nutrition as integral to recovery from a critical illness and to suggest
      that enteral feeding is efficient and effective at providing nutrition.

PMID- 11833631
TI  - Special feature: an approach to cardiac care in rural settings.
AB  - Rural people with cardiovascular disease-and the nurses caring for them-face
      unique health care challenges. Obstacles facing patients living in small rural
      communities include lack of critical care specialists, inadequate technological
      support, and inconsistent or variable levels of 24-hour patient care services
      requiring patients to travel to distant tertiary centers for advanced cardiac
      care. Rural critical care nurses face reduced access to continuing education and
      inservice presentations, professional isolation, and lack of anonymity. This
      article introduces "Mr Smith," a rancher with cardiovascular disease living in a
      rural Western state. In so doing, it reviews the issues and challenges faced by
      rural patients and nurses. In addition, the article describes a continuing
      education course developed to enhance collaboration between nurses working in
      rural settings and a tertiary medical center.

PMID- 11833632
TI  - Rating and quantification of manic syndromes.

PMID- 11833633
TI  - Practice parameter for the use of stimulant medications in the treatment of
      children, adolescents, and adults.
AB  - This practice parameter describes treatment with stimulant medication. It uses an
      evidence-based medicine approach derived from a detailed literature review and
      expert consultation. Stimulant medications in clinical use include
      methylphenidate, dextroamphetamine, mixed-salts amphetamine, and pemoline. It
      carries FDA indications for treatment of attention-deficit/hyperactivity disorder
      and narcolepsy.

PMID- 11833634
TI  - Practice parameter for the prevention and management of aggressive behavior in
      child and adolescent psychiatric institutions, with special reference to
      seclusion and restraint.
AB  - This parameter reviews the current state of the prevention and management of
      child and adolescent aggressive behavior in psychiatric institutions, with
      particular reference to the indications and use of seclusion and restraint. It
      also presents guidelines that have been developed in response to professional,
      regulatory, and public concern about the use of restrictive interventions with
      aggressive patients with regard to personal safety and patient rights. The
      literature on the use of seclusion, physical restraint, mechanical restraint, and
      chemical restraint is reviewed, and procedures for carrying out each of these
      interventions are described. Clinical and regulatory agency perspectives on these
      interventions are presented. Effectiveness, indications, contraindications,
      complications, and adverse effects of seclusion and restraint procedures are
      addressed. Interventions are presented to provide more opportunities to promote
      patient independence and satisfaction with treatment while diminishing the
      necessity of using restrictive procedures.

PMID- 11833635
TI  - A comparison of the nutritional value, sensory qualities, and food safety of
      organically and conventionally produced foods.
AB  - Given the significant increase in consumer interest in organic food products,
      there is a need to determine to what extent there is a scientific basis for
      claims made for organic produce. Studies comparing foods derived from organic and
      conventional growing systems were assessed for three key areas: nutritional
      value, sensory quality, and food safety. It is evident from this assessment that
      there are few well-controlled studies that are capable of making a valid
      comparison. With the possible exception of nitrate content, there is no strong
      evidence that organic and conventional foods differ in concentrations of various
      nutrients. Considerations of the impact of organic growing systems on nutrient
      bioavailability and nonnutrient components have received little attention and are
      important directions for future research. While there are reports indicating that
      organic and conventional fruits and vegetables may differ on a variety of sensory
      qualities, the findings are inconsistent. In future studies, the possibility that
      typical organic distribution or harvesting systems may deliver products differing
      in freshness or maturity should be evaluated. There is no evidence that organic
      foods may be more susceptible to microbiological contamination than conventional
      foods. While it is likely that organically grown foods are lower in pesticide
      residues, there has been very little documentation of residue levels.

PMID- 11833636
TI  - Microbial risks in mild hot smoking of fish.
AB  - Hot smoked fish should fulfill the requirements set up for ready-to-eat foods.
      The total bacterial count on the raw material is 10(3) to 10(5) CFU per cm2 of
      skin and 10(2) to 10(9) CFU per gram of intestines. Contamination with pathogenic
      bacteria is very low, mainly with Clostridium botulinum, Listeria monocytogenes,
      Staphylococcus aureus, and Vibrio parahaemolyticus. In the premises of low
      hygiene, the contamination may increase due to unsanitary procedures, rotation of
      assigned duties of workers, and airborne microorganisms during packing of the
      product. Hot smoking in mild conditions at temperature in the fish not exceeding
      65 degrees C and low concentration of salt does not inactivate all pathogens or
      inhibit bacteria during storage. Thus the required safety can be obtained only by
      using very fresh fish handled in hygienic conditions, controlling the processing
      and the plant hygiene in critical control points, and chilling of the product to
      about 2 degrees C. Most critical are the hygienic conditions in handling of the
      product after smoking. The use of preservatives for extending the shelf life of
      smoked fish is being investigated. High-quality shelf life of mild hot smoked
      mackerel at about 2 degrees C is at least 3 weeks.

PMID- 11833637
TI  - Factors affecting the moisture permeability of lipid-based edible films: a
      review.
AB  - Moisture transfers inside food products could be controlled or limited by the use
      of edible films. These are usually based on hydrophobic substances such as lipids
      to improve barrier efficiency. Water permeability of films is affected by many
      factors, depending on both the nature of barrier components, the film structure
      (homogeneous, emulsion, multilayer, etc.), crystal type, shape, size and
      distribution of lipids, and thermodynamics such as temperature, vapor pressure,
      or the physical state of water in contact to the films. After a brief
      presentation of lipids and hydrophobic substances used as moisture barrier, cited
      in the scientific literature, this article reviews all of the parameters
      affecting barrier performances of edible films and coatings.

PMID- 11833638
TI  - Bioanalysis in microfluidic devices.
AB  - Microfabricated bioanalytical devices (also referred to as laboratory-on-a-chip
      or micro-TAS) offer highly efficient platforms for simultaneous analysis of a
      large number of biologically important molecules, possessing great potential for
      genome, proteome and metabolome studies. Development and implementation of
      microfluidic-based bioanalytical tools involves both established and evolving
      technologies, including microlithography, micromachining, micro-electromechanical
      systems technology and nanotechnology. This article provides an overview of the
      latest developments in the key device subject areas and the basic
      interdisciplinary technologies. Important aspects of DNA and protein analysis,
      interfacing issues and system integration are all thoroughly discussed, along
      with applications for this novel "synergized" technology in high-throughput
      separations of biologically important molecules. This review also gives a better
      understanding of how to utilize these technologies as well as to provide
      appropriate technical solutions to problems perceived as being more fundamental.

PMID- 11833639
TI  - Stochastic theory of size exclusion chromatography by the characteristic function
      approach.
AB  - A general stochastic theory of size exclusion chromatography (SEC) able to
      account for size dependence on both pore ingress and egress processes, moving
      zone dispersion and pore size distribution, was developed. The relationship
      between stochastic-chromatographic and batch equilibrium conditions are discussed
      and the fundamental role of the 'ergodic' hypothesis in establishing a link
      between them is emphasized. SEC models are solved by means of the characteristic
      function method and chromatographic parameters like plate height, peak skewness
      and excess are derived. The peak shapes are obtained by numerical inversion of
      the characteristic function under the most general conditions of the exploited
      models. Separate size effects on pore ingress and pore egress processes are
      investigated and their effects on both retention selectivity and efficiency are
      clearly shown. The peak splitting phenomenon and peak tailing due to incomplete
      sample sorption near to the exclusion limit is discussed. An SEC model for
      columns with two types of pores is discussed and several effects on retention
      selectivity and efficiency coming from pore size differences and their relative
      abundance are singled out. The relevance of moving zone dispersion on separation
      is investigated. The present approach proves to be general and able to account
      for more complex SEC conditions such as continuous pore size distributions and
      mixed retention mechanism.

PMID- 11833640
TI  - Urea-formaldehyde resin monolith as a new packing material for affinity
      chromatography.
AB  - A urea-formaldehyde resin (UF) continuous bed has been prepared through in-situ
      condensation polymerization in a confined tube. The monolith is an agglomerate of
      2-microm irregular particles. Nitrogen adsorption shows that the monolith has a
      bimodal pore size distribution. It has low resistance to flow. A dyed monolith is
      obtained through modification of the UF monolith with Cibacron blue F3GA.
      Although its dye concentration and dynamic capacity are low compared to Sepharose
      type affinity media, the dyed monolith can separate some proteins in the affinity
      mode of liquid chromatography.

PMID- 11833641
TI  - Preparative separation of lappaconitine, ranaconitine, N-deacetyllappaconitine
      and N-deacetylranaconitine from crude alkaloids of sample Aconitum sinomontanum
      Nakai by high-speed counter-current chromatography.
AB  - Analytical high-speed counter-current chromatography (HSCCC) was used for the
      systematic selection and optimization of the two-phase solvent system to separate
      alkaloids from Aconitum sinomontanum Nakai. The optimum solvent systems CHCl3
      MeOH-0.3 M/0.2 M HCl (4:1.5:2, v/v) thus obtained led to the successful
      separation of lappaconitine, ranaconitine, N-deacetyllappaconitine and N
      deacetylranaconitine from 60 to 500 mg of crude alkaloid sample by preparative
      HSCCC separation.

PMID- 11833642
TI  - High-performance liquid chromatography determination of Zn-bacitracin in animal
      feed by post-column derivatization and fluorescence detection.
AB  - A sensitive and selective method is presented for the determination of Zn
      Bacitracin in adulterated animal feed by reversed-phase ion-pair high-performance
      liquid chromatography and post-column derivatization with o-phthalaldehyde prior
      to fluorescence detection. The calibration function was estimated to be between
      8.0 and 65.0 mg l(-1) of Zn-BC. The detection and quantification limits of the
      chromatographic method were 2.5 and 7.5 mg 1(-1), respectively. Using the
      extraction procedure of Zn-Bacitracin from the feedstuff that we recently
      proposed and applying this new chromatographic method, it was possible to detect
      this antibiotic at levels below 5 mg kg(-1) in different kinds of feedstuffs with
      a standard deviation less than 6.0%.

PMID- 11833643
TI  - Preparative isolation and purification of salvianolic acid B from the Chinese
      medicinal plant Salvia miltiorrhiza by high-speed counter-current chromatography.
AB  - High-speed counter-current chromatography was applied to the isolation and
      purification of salvianolic acid B from the Chinese medicinal plant Salvia
      miltiorrhiza Bunge. The crude salvianolic acid B was obtained by extraction with
      ethanol-water from S. miltiorrhiza Bunge. Preparative high-speed counter-current
      chromatography with a two-phase solvent system composed of n-hexane-ethyl acetate
      ethanol-water (3:7:1:9, v/v) was successfully performed yielding 342 mg
      salvianolic acid B at 98% purity from 500 mg of the crude extract in a one-step
      separation.

PMID- 11833644
TI  - Characterization of alkyl polyglycosides by both reversed-phase and normal-phase
      modes of high-performance liquid chromatography.
AB  - Alkyl polyglycosides today represent the most important sugar surfactant.
      Nonionic sugar surfactants produced via different synthetic routes are mixtures
      of alkyl homologues, oligomers, anomers and isomers. Alkyl homologues and
      oligomers of alkyl mono- and diglucosides were separated by reversed-phase high
      performance liquid chromatography (HPLC) with methanol-water as the mobile phase
      using a gradient elution. The gradient was optimized in respect to a simultaneous
      separation of alkyl glycosides according to their alkyl chain length and alkyl
      polyoxyethylene glucosides with regard to their length of the polyoxyethylene
      spacer. The separation of alkyl glycosides into alpha- and beta-anomers was
      carried out by normal-phase HPLC with isooctane-ethyl acetate (60:40, v/v)-2
      propanol in the gradient mode. Light scattering detection was used. Matrix
      assisted laser desorption ionization time-of-flight mass spectra of alkyl
      glucosides and dodecyl glucosides with oxyethylene spacer groups are presented.

PMID- 11833645
TI  - Characterisation of core-shell latexes by flow field-flow fractionation with
      multi-angle light scattering detection.
AB  - Flat channel asymmetrical flow field-flow fractionation with multi-angle light
      scattering (MALS) detection was used to study the swelling behaviour of core
      shell particles with either carboxylated or hydroxylated shells as a function of
      pH and ionic strength. The equilibration time of the most heavily carboxylated
      core-shells appeared to be of the order of several hours. At low ionic strength
      (5 mM), the carboxylated core-shells showed a definite swelling response to a
      change in pH in the range from 5 to 10, ranging from a hydrodynamic radius
      increase of 24 to 118%, depending on the degree of carboxylation. A much milder
      response was found for the change of the root mean square (r.m.s.) radius as
      measured with MALS, indicating that the scattering plane is moving inwards during
      the swelling process due to a decreasing density of the shell. The hydroxylated
      core-shells appeared to be inert to a change in pH. Also the response of two
      expanded (pH 10) carboxylated core-shells on increasing ionic strength was
      studied. Comparison of the results of these ionic strength experiments with
      theoretical predictions based on Donnan equilibrium led us to the conclusion that
      a significant amount of counter-ion condensation may take place in the shells.

PMID- 11833646
TI  - Migration behavior of metal complexes in capillary zone electrophoresis.
      Interpretation in terms of quantitative structure-mobility relationships.
AB  - Significant advances in metal ion analysis by capillary zone electrophoresis
      (CZE) have occurred as a consequence of using metal complexes with various
      organic and inorganic ligands. Metal-ligand complexes that contribute to metal
      speciation in solution have also gained the attention of researchers. An
      understanding of the molecular properties that control the separation and further
      insight into the migration mechanism call for a systematic analysis of
      relationships between migration parameters and charge and size characteristics of
      metal complexes. To perform such an investigation, a number multiparametric
      migration models derived from a generally valid equation for electrophoretic
      mobility as a function of charge density were developed. The models operating
      with tabular or readily calculated structural descriptors (in particular, metal
      atom electronegativity or effective charge) as well as with the formal charge and
      ligand number were evaluated using numerous sets of experimental migration data
      for inorganic and organic ligand complexes. Consistent--in a great many instances
      -approximation results confirm the separation mechanism for metal complexes in
      CZE as governed basically by differences in charge-to-size parameters, present a
      valuable and convincing selection of such parameters, possessing a definite
      physical meaning, and owing to the general validity of the multivariate
      regression approach, open new possibilities in its application to more complex
      (i.e., electrokinetic chromatographic) systems.

PMID- 11833647
TI  - Evaluation of different nucleic acid stains for sensitive double-stranded DNA
      analysis with capillary electrophoretic separation.
AB  - This paper outlines the first use of SYTOX Orange, SYTO 82 and SYTO 25 nucleic
      acid stains for on-column staining of double-stranded DNA (dsDNA) fragments
      separated by capillary electrophoresis (CE). Low-viscosity, replaceable
      poly(vinylpyrrolidone) (PVP) polymer solution was used as the sieving matrix on
      an uncoated fused-silica capillary. The effects of PVP concentration, electric
      field strength, and incorporated nucleic acid stain concentrations on separation
      efficiency were examined for a wide range of DNA fragment sizes. Our study was
      focused on using nucleic acid stains efficiently excitable at a wavelength of 532
      nm. Among the five tested nucleic acid stains, SYTOX Orange stain was shown to
      have the best sensitivity for dsDNA detection by CE. About a 500-fold lower
      detection limit was obtained compared to commonly used ethidium bromide and
      propidium iodide. SYTOX Orange stain also provided a wide linear dynamic range
      for direct DNA quantitation with on-line CE detection. Use of SYTOX Orange stain
      can greatly improve the measurement of DNA fragments by CE, which will enable an
      expanded set of applications in genomics and diagnostics.

PMID- 11833648
TI  - Ultra-low-temperature non-aqueous capillary electrophoretic separation--77 K
      fluorescence spectroscopic detection for the on-line identification of photo
      converted analytes of trans-resveratrol.
AB  - We demonstrate here, for the first time, that non-aqueous capillary
      electrophoresis (NACE) can be interfaced with any ultra-low-temperature (ULT)
      separation method and 77 K fluorescence spectroscopy (FS). This novel ULT-NACE-FS
      system consists of a modular CE system, a dry ice bath, and instrumentation for
      77 K fluorescence detection. The ULT-NACE method serves to separate structurally
      similar molecules by a combination of a low electrophoresis current and a high
      voltage at approximately -70 degrees C. When the ULT-NACE-separated analytes move
      into the quartz Dewar flask and traverse into the capillary detection window,
      liquid nitrogen was added, thus freezing the separating analyte zones, allowing
      the collection of 77 K fluorescence spectra for on-line spectral fingerprint
      identification. The first application of the ULT-NACE-FS system is described for
      the analysis of photo-converted analytes of trans-resveratrol; prospects and
      future applications of ULT-NACE-FS are also briefly addressed.

PMID- 11833649
TI  - Centrifugal concentrator for the substitution of nitrogen blow-down micro
      concentration in dioxin/polychlorinated biphenyl sample preparation.
AB  - A centrifugal concentrator was applied for the substitution of nitrogen blow-down
      micro-concentration in dioxin/PCB sample preparation. Automation was achieved
      through this apparatus and resulted in significant improvements in sample
      preparation productivity, along with excellent reproducibility and recovery rate
      of dioxin/PCB. Mean recoveries of dioxin congeners were 90-106%, respectively.

PMID- 11833650
TI  - Isolation of the lignan secoisolariciresinol diglucoside from flaxseed (Linum
      usitatissimum L.) by high-speed counter-current chromatography.
AB  - High-speed counter-current chromatography was successfully used for the isolation
      and purification of secoisolariciresinol diglucoside, a bioactive lignan from
      flaxseed (Linum usitatissimum L.). The solvent system consisted of tert.
      butylmethyl ether-n-butanol-acetonitrile-water (1:3:1:5). The purity and identity
      of the isolated compound was checked by high-performance liquid chromatography
      analysis in combination with mass spectrometry and NMR measurements.

PMID- 11833651
TI  - Reversed-phase argentation high-performance liquid chromatography in
      phytochemical analysis of ginkgolic acids in leaves from Ginkgo biloba L.
AB  - A reversed-phase argentation high-performance liquid chromatographic method has
      been achieved for the determination of ginkgolic acids. Liquid chromatography
      coupled with electrospray ionization (ESI) mass spectrometry in the negative ion
      mode is applied to identify ginkgolic acids from ginkgo leaves. The leaves are
      extracted with ethanol and then cleaned-up by extraction of analytes with hexane
      after addition of an acidified saturated solution of sodium sulfate and siliceous
      earth to the matrix solution. Ginkgolic acids are determined within 30 min on a
      C18 column with methanol-5% aqueous acetic acid (90:10) containing 0.03 mol l(-1)
      silver nitrate as eluent and with ultraviolet detection at 310 nm. Addition of
      silver ions as complexation agent into the mobile phase decreases retention time
      of ginkgolic acids with an unsaturated side chain. Four ginkgolic acids are
      successfully separated from each other and from other interfering components by
      the high selectivity of reversed-phase argentation HPLC, which is confirmed by
      the spectra identification. The average recovery of the method is around 97%.
      Good reproducibility is obtained with relative standard deviations varying from 2
      to 5%.

PMID- 11833652
TI  - Optical anisotropy of a pig tendon under compression.
AB  - The proximal region of the superficial digital flexor tendon of pigs passes under
      the tibiotarsal joint, where it is subjected to compressional and tensional
      forces. This region was divided into a surface portion (sp), which is in direct
      contact with the bone and into a deep portion (dp), which is the layer opposite
      the articulating surface. The purpose of this work was to analyse the
      distribution and organisation of the collagen bundles and proteoglycans in the
      extracellular matrix in sp and dp. Toluidine-blue-stained sections were analysed
      under a polarising microscope. Strong basophilia and metachromasia were observed
      in sp, demonstrating accumulation of proteoglycan in a region bearing
      compression, but the intensity was reduced the further layers were from the bone.
      Linear dichroism confirmed that the glycosaminoglycan molecules were disposed
      predominantly parallel to the longest axis of the collagen fibrils. Birefringence
      analysis showed a higher molecular order and aggregation of the collagen bundles
      in areas where the tension was more prominent. The crimp pattern was more regular
      in dp than in sp, probably as a requirement for tendon stretching. The optical
      anisotropy exhibited by the collagen bundles also confirmed the helical
      organisation of the collagen bundles in the tendon. Hyaluronidase digestion
      caused a decrease in the basophilia, but this was not eliminated, supporting the
      idea that in the matrix, proteoglycans are not completely available to the enzyme
      action.

PMID- 11833653
TI  - Soft-tissue anatomy of the extant hominoids: a review and phylogenetic analysis.
AB  - This paper reports the results of a literature search for information about the
      soft-tissue anatomy of the extant non-human hominoid genera, Pan, Gorilla, Pongo
      and Hylobates, together with the results of a phylogenetic analysis of these data
      plus comparable data for Homo. Information on the four extant non-human hominoid
      genera was located for 240 out of the 1783 soft-tissue structures listed in the
      Nomina Anatomica. Numerically these data are biased so that information about
      some systems (e.g. muscles) and some regions (e.g. the forelimb) are over
      represented, whereas other systems and regions (e.g. the veins and the lymphatics
      of the vascular system, the head region) are either under-represented or not
      represented at all. Screening to ensure that the data were suitable for use in a
      phylogenetic analysis reduced the number of eligible soft-tissue structures to
      171. These data, together with comparable data for modern humans, were converted
      into discontinuous character states suitable for phylogenetic analysis and then
      used to construct a taxon-by-character matrix. This matrix was used in two tests
      of the hypothesis that soft-tissue characters can be relied upon to reconstruct
      hominoid phylogenetic relationships. In the first, parsimony analysis was used to
      identify cladograms requiring the smallest number of character state changes. In
      the second, the phylogenetic bootstrap was used to determine the confidence
      intervals of the most parsimonious clades. The parsimony analysis yielded a
      single most parsimonious cladogram that matched the molecular cladogram.
      Similarly the bootstrap analysis yielded clades that were compatible with the
      molecular cladogram; a (Homo, Pan) clade was supported by 95% of the replicates,
      and a (Gorilla, Pan, Homo) clade by 96%. These are the first hominoid
      morphological data to provide statistically significant support for the clades
      favoured by the molecular evidence.

PMID- 11833654
TI  - The transcription factor cSox2 and Neuropeptide Y define a novel subgroup of
      amacrine cells in the retina.
AB  - The retina has been extensively used as a model to study the mechanisms
      responsible for the production of different neural cell phenotypes. The
      importance of both extrinsic and intrinsic cues in these processes is now
      appreciated and numerous transcription factors have been identified which are
      required for both neuronal determination and cell differentiation. In this study
      we have analysed the expression of the transcription factor Sox2 during
      development of the chick retina. Expression was found in the proliferating cells
      of the retina during development and was down regulated by nearly all cell types
      as they started to differentiate and migrate to the different layers of the
      retina. In one cell type, however, Sox2 expression was retained after the cells
      have ceased division and migrated to their adult location. These cells formed two
      rows located on either side of the inner plexiform layer and were also positive
      for Neuropeptide Y, characteristics which indicate that they were a subpopulation
      of amacrine cells. The expression of Sox2 by only this population of post-mitotic
      neurones makes it possible to follow these cells as they migrate to their adult
      location and shows that they initially form a single row of cells which
      subsequently divides to form the double row seen in the adult tissue. We suggest
      that retained expression of Sox2 is involved in directing the differentiation of
      these cells and is an early marker of this cell type.

PMID- 11833656
TI  - Predominant neuronal B-cell loss in L5 DRG of p75 receptor-deficient mice.
AB  - The significance of the p75 low-affinity neurotrophin receptor, for the
      maintenance and survival of DRG cells, was studied in p75-deficient mice.
      Perikarya of the L5 DRG of 12-week-old p75 receptor-deficient mice and healthy
      Balb C mice were compared using stereological techniques. Following systematic
      sampling, the optical fractionator and the planar vertical rotator were used to
      estimate the number and mean volume of the cell bodies of the two neuronal
      subpopulations. The loss of B-cells was 57% (P < 0.00001), numbers being 7300 (CV
      = 0.12) in controls and 3100 in p75 receptor-deficient mice (CV = 0.18). Also, A
      cells showed a significant loss of 39% (P < 0.0001), numbers being 2600 (CV =
      0.12) in control mice and 1500 (CV = 0.16) in p75 receptor-deficient mice. The
      volume of A-cells was reduced by 30% (P<0.01), from 24.700 microm3 (CV=0.17)
      perikarya in p75 knock-out mice to 15.100 microm3 (CV=0.17) in controls. B-cell
      volume did not change significantly. It is concluded that the p75 receptor plays
      a major role in the survival of DRG cells. The predominant loss of small B-cells
      indicates that the effect of neurotrophins is dependent upon the presence of the
      p75 low-affinity receptor.

PMID- 11833657
TI  - Ultrastructural and immunohistochemical study of the basal apparatus of solitary
      cilia in the human oviduct epithelium.
AB  - The basal apparatus of the solitary cilium is composed of the basal body, an
      associated centriole and the basal body-associated structures. To see the
      connection between the basal body and the centriole, we studied the basal
      apparatus of solitary cilia in human oviductal secretory cells by electron
      microscopy and immunohistochemistry. A single centriole was present in the
      vicinity of the basal body of a solitary cilium. The basal body and the single
      centriole were interconnected by one or two bundles of thin filaments with a few
      periodic striations. We have called these bundles the striated connector. The
      periodicity of striations in the striated connector measured 55 +/- 6 nm, about
      15 nm shorter than that of striated rootlets. The striated connector was
      immunolabelled with R67 antibody specific to striated rootlets, indicating that
      they are composed of common molecule(s). Although the true function of the
      connector is unknown as yet, it could play an important role for stabilising the
      basal body in the apical cytoplasm.

PMID- 11833655
TI  - Fibroblast growth factor-2 induces astroglial and microglial reactivity in vivo.
AB  - A role for fibroblast growth factor-2 (FGF-2) has been proposed in mediating the
      glial response to injury in the central nervous system (CNS). We have tested this
      possibility in vivo, by injecting FGF-2 into the cerebrospinal fluid (CSF) of the
      brain ventricles of young rats and analysing glial cells in the anterior
      medullary velum (AMV), which partly roofs the IVth ventricle. FGF-2 was
      administered at two different doses, low FGF-2 (500 ng mL(-1) CSF) and high FGF-2
      (10 microg mL(-1) CSF), and saline vehicle was injected in controls. Injections
      were performed twice daily for three days, commencing at postnatal day (P) 6, and
      AMV were analysed at P9, using immunohistochemistry and Western blotting. Glial
      cells were unaffected by treatment with saline or low FGF-2, whereas high FGF-2
      induced reactive changes in glial cell types: (1) there was increased GFAP
      expression in astrocytes, demonstrated by Western blot and immunohistochemistry,
      and astrocytes appeared hypertrophic, with increased process thickness and
      number; (2) the number of ED1 labelled microglia/macrophages was doubled, from 47
      +/- 6 to 114 +/- 17 cells per field (0.75 mm2; values are mean +/- SEM), and
      microglia appeared activated, with a multipolar and granular appearance; (3) NG2
      positive glial cells appeared more fibrous and there was increased density of
      processes, although there was no significant increase in their number; (4)
      oligodendrocyte somata were enlarged and there was a loss of myelin sheaths. The
      results show that at high CSF titres of FGF-2 induce glial reactivity in vivo and
      support a role for FGF-2 in the pathology of CNS injury and EAE.

PMID- 11833658
TI  - Epithelial-myoepithelial carcinoma of the parotid gland with adenoid cystic
      carcinoma-like features: a case report with immunohistochemical study.
AB  - A 69-year-old japanese female with epithelial myoepithelial carcinoma (EMC) in
      the parotid gland is reported. The tumor, 3.5 x 4.0 x 1.5 cm in size, was located
      in the left parotid gland. Histopathological examination of the surgically
      removed tumor revealed that it was composed of double-layered, tubule-like
      structures formed by inner eosinophilic ductal cells and outer clear cells, as
      well as solid clear cell nests. The unique histological finding of this tumor was
      that it had a cribriform-like arrangement of myoepithelial cells resembling an
      adenoid cystic carcinoma. On the other hand, the typical ductal and myoepithelial
      components of EMC showed the usual biphasic pattern and the expected
      immunophenotypes, with expression of low molecular weight cytokeratins, CAM 5.2
      and EMA in the ductal part, and smooth muscle actin, S-100 protein, and vimentin
      in the myoepithelial component.

PMID- 11833659
TI  - Radioprotective effects of miso (fermented soy bean paste) against radiation in
      B6C3F1 mice: increased small intestinal crypt survival, crypt lengths and
      prolongation of average time to death.
AB  - The radioprotective effect of miso, a fermentation product from soy bean, was
      investigated with reference to the survival time, crypt survival and jejunum
      crypt length in male B6C3F1 mice. Miso at three different fermentation stages
      (early-, medium- and long-term fermented miso) was mixed in MF diet into biscuits
      at 10% and was administered from 1 week before irradiation. Animal survival in
      the long-term fermented miso group was significantly prolonged as compared with
      the short-term fermented miso and MF cases after 8 Gy of 60Co-gamma-ray
      irradiation at a dose rate of 2Gy min(-1). Delay in mortality was evident in all
      three miso groups, with significantly increased survival. At doses of 10 and 12
      Gy X-irradiation at a dose rate of 4 Gy min(-1), the treatment with long-term
      fermented miso significantly increased crypt survival. Also the protective
      influence against irradiation in terms of crypt lengths in the long-term
      fermented miso group was significantly greater than in the short-term or medium
      term fermented miso and MF diet groups. Thus, prolonged fermentation appears to
      be very important for protection against radiation effects.

PMID- 11833660
TI  - Repair of articular cartilage on the surface of heat-treated bone by
      transplantation of cultured chondrocytes.
AB  - The present study addresses clinical problems associated with the degeneration of
      articular cartilage, which occurs when heat-treated bone with articular cartilage
      is used for re-implantation after resection of malignant bone tumors adjacent to
      the joints. We therefore evaluated the effect of transplantation of chondrocytes
      embedded in collagen gel on the surface of heat-treated bone. A cylindrical
      complex of bone and articular cartilage 6 mm in diameter was resected from
      rabbits' patellar grooves and treated in saline at 60 degrees C for 30 min. In
      Group A, articular cartilage was resected from the complex and the remaining bone
      was returned to the patellar groove. Then, autologous chondrocytes cultured in
      collagen gel were transplanted and covered with periosteum. As controls, the
      original complex of heat-treated bone and articular cartilage (Group B) and heat
      treated bone directly covered with periosteum (Group C) was returned to the
      patellar groove. In Group A, histological study showed that round cells were
      mainly observed and the matrix was well stained with Safranin O in the repair
      tissue after 24 weeks. The repair tissue was as thick as the adjacent normal
      cartilage. Immunohistological study detected type-II collagen and chondroitin-6
      sulphate (3B3+) in the matrix of the repair tissue, but not type-I collagen. The
      repair tissue was consequently cartilaginous in Group A. The repair tissue was
      not cartilaginous or was degenerative in the control groups. We believe that this
      modality of heat-treated joints will contribute to limb salvage reconstruction
      after resection of malignant bone tumors adjacent to the joints.

PMID- 11833661
TI  - A formula based on body length for determining the size of an uncuffed
      endotracheal tube for pediatric cardiac anesthesia.
AB  - Three hundred and thirty-four pediatric patients less than 4 years old who
      underwent surgery for congenital heart disease were retrospectively studied to
      devise a practical formula for predicting the appropriate size for an uncuffed
      endotracheal tube for pediatric cardiac anesthesia. Furthermore, this formula was
      compared with that for non-cardiac anesthesia obtained from 409 patients without
      congenital heart disease. A simple regression equation between tube size and body
      length resulted in the simple predictive formula: "tube size = 0.04 x body length
      + 1.6" for pediatric cardiac anesthesia. This formula had the same slope and an
      approximately 0.3 mm larger intercept on the Y-axis compared with that for
      pediatric non-cardiac anesthesia. Therefore, a one-size larger endotracheal tube
      is more suitable for use in pediatric cardiac anesthesia than in pediatric non
      cardiac anesthesia for the same body length.

PMID- 11833662
TI  - A real-time classification system of thalassemic pathologies based on artificial
      neural networks.
AB  - Thalassemias are pathologies that derive from genetic defects of the globin
      genes. The most common defects among the population affect the genes that are
      involved in the synthesis of alpha and beta chains. The main aspects of these
      pathologies are well explained from a biochemical and genetic point of view. The
      diagnosis is fundamentally based on hematologic and genetic tests. A genetic
      analysis is particularly important to determine the carriers of alpha
      thalassemia, whose identification by means of the hematologic parameters is more
      difficult in comparison with heterozygotes for alpha-thalassemia. This work
      investigates the use of artificial neural networks (ANNs) for the classification
      of thalassemic pathologies using the hematologic parameters resulting from
      hemochromocytometric analysis only. Different combinations of ANNs are reported,
      which allow thalassemia carriers to be discriminated from normals with 94%
      classification accuracy, 92% sensitivity, and 95% specificity. On the basis of
      these results, an automated system that allows real-time support for diagnoses is
      proposed. The automated system interfaces a hemochromo analyzer to a simple PC.

PMID- 11833663
TI  - Comparison of health state utilities using community and patient preference
      weights derived from a survey of patients with HIV/AIDS.
AB  - OBJECTIVES: The authors compare health state utilities derived from a national
      survey of patients with HIV/AIDS to represent community-based preferences with
      utilities derived from the same survey representing patient preferences; explore
      the relationships between these utilities and the dimensions of the SF-6D health
      state classification; and examine the implications of differences in the source
      of utilities for a cost-effectiveness analysis of early treatment of patients
      with HIV/AIDS. METHODS: The authors derived community-based standard gamble (SG)
      utilities using an algorithm developed for the SF-6D health state classification
      system. The authors derived patient SG utilities from HIV/AIDS patient rating
      scale self-assessments using a power transformation. Data were from the HIV Cost
      and Services Utilization Study, a probability sample of 2864 HIV-infected adults
      receiving care in the United States in 1996. RESULTS: Patient SG utilities were
      higher than community SG utilities by 4% to 9% (0.979 vs. 0.937, 0.910 vs. 0.841,
      and 0.845 vs. 0.778; P < 0.001 for all comparisons). In regression analyses,
      patient SG utilities were less influenced by physical functioning, pain, and
      mental health dimensions of the SF-6D. The base case results of a cost
      effectiveness analysis comparing early antiretroviral therapy to deferred therapy
      were unaffected by the choice between community ($20,100 per quality-adjusted
      life year) and patient ($18,400 per quality-adjusted life year) perspectives. The
      impact of the choice of utilities remained small in sensitivity analyses that
      varied the influence of treatment side effects on utilities and the initial
      symptom status of patients. CONCLUSION: There are differences between community
      and patient utilities for HIV/AIDS health states, although even when treatment
      side effects are important, these differences may not affect cost-effectiveness
      ratios.

PMID- 11833664
TI  - Predicting elderly outpatients' life-sustaining treatment preferences over time:
      the majority rules.
AB  - BACKGROUND: This study describes longitudinal changes in the composition and
      accuracy of modal life-sustaining treatment preferences as predictors of
      patients' treatment preferences. METHOD: Healthy outpatients age 65 and older and
      their surrogate decision makers recorded preferences for 4 treatments in 9
      hypothetical illness scenarios 3 times over a period of 2 years. A statistical
      prediction model, based on patients' modal preferences, was created using initial
      responses and updated 2 years later. RESULTS: When reestimating the model at 2
      years, 4 of 27 items in the model created using baseline responses no longer
      reached the threshold for inclusion, but 5 new items did meet criteria. All modal
      preference changes reflected a trend toward refusing treatment. Both the original
      and updated models were more accurate in predicting patients' preferences than
      were surrogates making concurrent predictions. Adding covariates (e.g., gender,
      age, presence of plans for future medical care) did not alter the model's
      predictive superiority over surrogates. CONCLUSIONS: Models using modal
      preferences are useful to patients, surrogates, and physicians when trying to
      accurately discern end-of-life treatment choices, but the models must be updated
      periodically.

PMID- 11833665
TI  - A simulation model of policies directed at treating tobacco use and dependence.
AB  - OBJECTIVES: The authors develop a simulation model to predict the effects on quit
      rates and cost-effectiveness of different smoking treatment policies. METHODS: A
      decision theoretic model of quit behavior is first developed that incorporates
      the decision to quit and the choice of treatment. A policy model then examines
      the effect on quit attempts and quit rates of policies to cover the costs of
      different combinations of treatments and to require health care providers to
      conduct brief interventions. The model incorporates substitution between
      treatments and effects of policies on treatment effectiveness. The cost per quit
      is also calculated for each policy. RESULTS: The model of quit behavior predicts
      a 1-year quit rate of 4.5% for the population of smokers. The policy model
      predicts a 37% increase in quit rates from a policy that combines mandated brief
      interventions with coverage of all proven tobacco treatments. Smaller effects are
      predicted from policies that provide more restricted coverage of treatments,
      especially those limited to behavioral treatment. Payments for brief
      interventions alone increase quit rates by about 7%. Brief intervention and
      behavioral therapy policies had lower costs per quit but yield substantially
      fewer additional quits than policies that cover pharmacotherapy. There is,
      however, considerable variation around these estimates depending on assumptions
      about the effects of policy on treatment use, substitution between treatments,
      and treatment effectiveness. CONCLUSION: Tobacco treatment policies, especially
      those with broad and flexible coverage, have the potential to substantially
      increase smoking quit rates. However, further research is needed on the effect of
      payment policies on the use and effectiveness of tobacco treatments.

PMID- 11833667
TI  - Effects of baseline risk information on social and individual choices.
AB  - This article analyzes preferences for risk reductions in the context of
      individual and societal decision making. The effect of information on baseline
      risk is analyzed in both contexts. The results indicate that if individuals are
      to imagine that they suffer from 1 low-risk and 1 high-risk ailment, and are
      offered a specified identical absolute risk reduction, a majority will ceteris
      paribus opt for treatment of the low-risk ailment. A different preference
      structure is elicited when priority questions are framed as social choices. Here,
      a majority will prefer to treat the high-risk group of patients. The preference
      reversal demonstrates the extent to which baseline risk information can influence
      preferences in different choice settings. It is argued that presentation of
      baseline risk information may induce framing effects that lead to nonoptimal
      resource allocations. A solution to this problem may be to not present group
      specific baseline risk information when eliciting preferences.

PMID- 11833666
TI  - Physicians' attitudes toward health care rationing.
AB  - BACKGROUND: Optimal allocation of health care resources under a limited budget is
      controversial. Particularly important questions are whether rationing decisions
      should be based on efficiency considerations alone or in combination with equity
      considerations, and who should be in charge of such decisions. In this study, the
      authors sought to understand the position of Swiss physicians toward rationing
      using a previously developed rationing scenario. METHODS: The authors examined
      the acceptability of various scenarios implementing health care rationing in a
      mail survey of 1,184 physicians practicing in Geneva, Switzerland. Respondents
      were asked to choose between providing a suboptimal cancer screening test A to
      the whole population, which would save 1,000 lives, or selecting half of the
      population to receive a better but more expensive test B, which would save 1,100
      lives. Physicians were randomly assigned to 3 versions of the scenario:
      Beneficiaries of test B could be chosen by lottery, on a first-come-first-served
      basis, or by medical associations. RESULTS: Only 26% of physicians chose the more
      effective selective rationing option; this proportion was lowest when test
      beneficiaries were selected by lottery (14%), intermediate for the first-come
      first-served-scenario (26%), and highest when selection was left to medical
      associations (39%; P < 0.001). Hospital-based physicians and general
      practitioners were less likely to endorse selective rationing than community
      based physicians and specialists. CONCLUSION: Swiss physicians appear to be more
      concerned about equal allocation of health services than about maximizing health
      in society, and they prefer physicians to be in charge of rationing decisions.

PMID- 11833669
TI  - Law and ethics.

PMID- 11833668
TI  - Effect of framing as gain versus loss on understanding and hypothetical treatment
      choices: survival and mortality curves.
AB  - BACKGROUND: Presentation of information using survival or mortality (i.e.,
      incidence) curves offers a potentially powerful method of communication because
      such curves provide information about risk over time in a relatively simple
      graphic format. However, the effect of framing as survival versus mortality on
      understanding and treatment choice is not known. METHODS: In this study, 451
      individuals awaiting jury duty at the Philadelphia City Courthouse were
      randomized to receive 1 of 3 questionnaires: (1) survival curves, (2) mortality
      curves, or (3) both survival and mortality curves. Each questionnaire included a
      brief description of a hypothetical treatment decision, survival curve graphs
      and/or mortality curve graphs presenting the outcome of the treatment, and
      questions measuring understanding of the information contained in the graphs and
      preference for undergoing treatment. After completing a brief practice exercise,
      participants were asked to answer questions assessing their ability to interpret
      single points on a curve and the difference between curves, and then to decide
      whether they would choose to undergo preventive surgery for 3 different scenarios
      in which the benefit of surgery varied. RESULTS: Participants who received only
      survival curves or who received both survival and mortality curves were
      significantly more accurate in answering questions about the information than
      participants who received only mortality curves (P < 0.05). For 2 of the 3
      treatment presentations, participants who received only mortality curves were
      significantly less likely to prefer preventive surgery than participants who
      received survival curves only or both survival and mortality curves (P < 0.05).
      The effect of framing on understanding was greatest among participants with less
      than a college education and among non-Caucasian participants. CONCLUSION:
      Framing graphic risk information as chance of death over time results in lower
      levels of understanding and less interest in preventive surgery than framing as
      chance of survival over time.

PMID- 11833670
TI  - Pharmaceutical safety of red blood cells from whole blood donation in a military
      transfusion center.

PMID- 11833671
TI  - A new autoantibody in celiac disease.
AB  - A 74-year-old female patient with therapy-resistant sprue (celiac disease) and a
      new IgA autoantibody is presented. This autoantibody was demonstrated by
      immunofluorescence and differs from the conventional antibody against type 3
      connective tissue (so-called endomysium antibody). It reacts predominantly with
      the muscularis and less strongly with the muscularis mucosae of the monkey
      esophagus. The reaction is not retiform but punctiform; the typical reaction
      sites of the antibody against type 3 connective tissue are negative. Especially
      on esophageal sections the antibody can be mistaken for the characteristic
      antibody directed against tissue transglutaminase, in particular at low
      magnification. The antigen of the new antibody is as yet unknown.

PMID- 11833672
TI  - Rapid typing of the codon 129 polymorphism of the human prion protein gene by
      combined real-time PCR and melting curve analysis.
AB  - Homozygosity of methionine (m/m) at amino acid residue 129 (codon 129) of the
      human prion protein (PrP) has been reported for all so far analyzed cases of the
      new variant Creutzfeldt-Jakob disease (vCJD). This contrasts with its general
      distribution in the healthy Caucasian population of only about 43%. For this
      reason a predisposition for carriers of the corresponding genotype to develop
      vCJD after infection with the bovine spongiform encephalopathy (BSE) agent is
      assumed, and PCR based methods such as allele-specific oligonucleotide
      hybridization or restriction analysis and sequencing have been developed for
      codon 129 genotyping. These methods are cumbersome and time-consuming and the
      need for extensive post-amplification manipulations increases the risk of carry
      over contamination with amplified products. To overcome these shortcomings, the
      authors developed a real-time PCR assay on the LightCycler (LC) instrument
      combining PCR and temperature melting curve analysis (Tm) in a closed vessel
      format. Forty-six swabs and blood samples from healthy donors were tested. Of
      these 23 (50%) were heterozygous at codon 129, 4 (8.7%) homozygous for valine and
      19 (41.3%) homozygous for methionine. Accuracy of LC-genotyping was confirmed by
      automated sequencing of the amplified products. Taken together, genotyping of the
      codon 129 polymorphism by combined LC-PCR and melting-curve analysis with the LC
      instrument is a reliable and easy to perform method even in a screening context
      with numerous samples. Results can be obtained within 2 hours, including sample
      preparation.

PMID- 11833673
TI  - Validation of a new automated immunoassay for measurement of intact osteocalcin.
AB  - Bone turnover is assessed indirectly by measurement of biochemical markers of
      bone turnover. Osteocalcin, a 49-amino-acid protein is a major noncollagenous
      protein of bone matrix, synthesized by osteoblasts and odontoblasts. Various
      assays exist for assessment of osteocalcin and concentrations in the same serum
      or plasma sample may vary enormously. The used antibodies may recognize intact
      osteocalcin and/or circulating fragments of osteocalcin. We here describe and
      validate a new automated immunoassay system for measurement of intact osteocalcin
      (DPC IMMULITE assay) using monoclonal antibodies (mouse) against the C-terminus
      of osteocalcin (AA 44-49). For detection polyclonal antibodies (goat) directed
      against the N-terminus (AA 1-17) conjugated with alkaline phosphatase are used.
      While different laboratory assays show marked clinical discordance, we evaluated
      our results comparatively to an established IRMA method (Nichols). We observed a
      highly significant correlation between both assays (r = 0.9352, p < 0.0001, n =
      286) for healthy persons and also for patient samples (osteoporosis, diabetes
      type 1, rheumatoid arthritis). Very low inter- and intraassay covariance as well
      as highly significant linearity (analytical recovery near 100%) tested by serial
      dilutions were demonstrated for the DPC IMMULITE intact osteocalcin assay. We
      conclude that the IMMULITE assay is a useful method for assessment of intact
      osteocalcin giving valuable results in comparison to an established non-automated
      assay.

PMID- 11833674
TI  - Cytomegalovirus as a hepatotropic virus.
AB  - Hepatitis is a frequent complication of cytomegalovirus infection in the
      immunocompetent as well as the immunocompromised host. Current knowledge of liver
      involvement in different groups of subjects undergoing cytomegalovirus infection,
      such as congenitally infected newborns, immunocompetent adults, transplant
      recipients and AIDS patients, will be summarized in this chapter. Furthermore, a
      recently identified population at risk for cytomegalovirus infection,
      hepatopathic patients, will be described.

PMID- 11833675
TI  - Comparison of three dsDNA-ELISAs with regard to their efficiency in the diagnosis
      of systemic lupus erythematosus.
AB  - We compared the performance of three commercially available anti-double-stranded
      DNA antibody ELISA kits with respect to their precision, accuracy, linearity, and
      the detection limit. We tested six sets of patients (lupus erythematosus,
      scleroderma, rheumatoid arthritis, psoriatic arthritis, hepatitis C,
      malignancies) to assess specificity, sensitivity, and diagnostic efficiency of
      the three assays. The diagnostic efficiency of the Crithidia luciliae
      immunofluorescence test was analyzed as a reference. The sensitivity of the
      evaluated enzyme immunoassays ranged from 55.6 to 66.7%, the specificity from
      98.4 to 100%, and the diagnostic efficiency from 90.2-92.7%. All ELISAs were
      superior to the immunofluorescence test, both with respect to sensitivity,
      specificity, and diagnostic efficiency. The commercial kits tested were
      comparable with respect to their performance characteristics.

PMID- 11833676
TI  - Diagnosis of pheochromocytoma.
AB  - The purpose of this article is to give an overview on recent advances in the
      diagnosis, localization by imaging and treatment of pheochromocytoma.
      Pheochromocytoma is a mostly benign tumor (malignancy rate 10-15%) which arises
      from chromaffin cells with excessive catecholamine production and secretion. Most
      tumors are localized in the adrenals but 15-18% of the lesions are found
      extraadrenally (paragangliomas). Pheochromocytoma is a rare form of secondary
      hypertension; it can also be found as a feature of familial disease (e.g. von
      Hippel-Lindau disease, MEN type II) due to genetic mutations of several genes
      that have been identified recently. In familial pheochromocytoma molecular
      genetic analysis has improved the diagnostic modalities. In such patients the
      tumor can occur bilaterally and patients often remain normotensive until the
      tumor produces sufficient catecholamines to have hemodynamic effects. The extreme
      importance of recognizing this tumor is evident from the fact that it can be
      successfully removed in about 90% of the cases, whereas if unrecognized the tumor
      poses great risk of death or devastating complications. Diagnostic screening
      includes measurement of catecholamines and their metabolites (metanephrines) in
      plasma and/or urine. Furthermore, pharmacological testing (e.g. clonidine
      suppression test) may be indicated in patients with moderately elevated
      catecholamines or when the diagnosis is still uncertain. Several imaging
      techniques are applied to localize the tumor. Abdominal CT scan is still
      considered the "gold standard" since about 98% of the tumors lie
      infradiaphragmatically. Magnetic resonance imaging (MRI) and MIBG-scanning are
      other useful methods. Recently, positron emission tomography (PET) based
      techniques have also been developed. After the diagnosis is made tumor removal
      following pharmacological pretreatment is the decisive therapeutic measure.

PMID- 11833677
TI  - Molecular biology of partial D and weak D: implications for blood bank practice.
AB  - Two genes, RHD and RHCE, encode the antigens of the RH blood group system. The
      clinically most important antigen D is determined by the presence of a functional
      and grossly normal RHD gene. About 18% of Europeans do not express an antigen D,
      most often but not always caused by the RHD gene deletion. Rhesus negative
      phenotypes in Africans are caused by the RHD gene deletion, the RHD pseudogene
      RHD psi, and the Cde(s) allele. About 1% of Europeans carry RHD alleles with
      aberrant structures encoding for diminished D-immunoreactivity. In Africans the
      frequency of aberrant RHD alleles is much higher. Aberrant RHD alleles encode
      partial D, some of which were dubbed D categories, and weak D. Since we defined
      the molecular basis of the RHD deletion, a specific detection of heterozygous
      carriers became feasible.

PMID- 11833678
TI  - Simple, rapid and sensitive determination of epinephrine and norepinephrine in
      urine and plasma by non-competitive enzyme immunoassay, compared with HPLC
      method.
AB  - BACKGROUND: Measurement of the concentration of the free catecholamines
      epinephrine (adrenalin) and norepinephrine (noradrenalin) in humans is used for
      the diagnosis of pheochromocytoma and related diseases. METHODS: A non
      competitive enzyme-linked immunosorbent assay (CatCombi ELISA) kit for the
      measurement of epinephrine and norepinephrine concentrations in plasma and urine
      was developed and validated. The assay procedure consists of sample extraction,
      chemical and enzymatic derivatization and immunological reaction steps. A sample
      volume of 10 microL urine or 300 microL EDTA plasma is required for duplicate
      determinations of both catecholamines. For method comparison we used a reversed
      phase HPLC by Chromsystems after extraction by aluminium oxide with
      electrochemical detection for the determination of epinephrine and
      norepinephrine. RESULTS: The CatCombi ELISA is accurate, sensitive, specific, and
      precise. Linear regression analysis of epinephrine and norepinephrine
      concentrations measured with the ELISA and with HPLC yielded highly significant
      correlations. CONCLUSIONS: The CatCombi ELISA kit as an alternative to HPLC
      methods is very useful for clinical applications as well as for basic research
      where a simple, rapid, accurate and reproducible assay for epinephrine and
      norepinephrine determinations is required.

PMID- 11833679
TI  - A comparison of the antimicrobial efficacy of three calcium hydroxide
      formulations on human dentin infected with Enterococcus faecalis.
AB  - This study compared the antibacterial efficacy of three different formulations of
      calcium hydroxide by using human dentin specimens that were infected with
      Enterococcus faecalis. After exposure to three forms of calcium hydroxide
      (calcium hydroxide mixed with distilled water, calcium hydroxide mixed with 0.2%
      chlorhexidine, and calcium hydroxide mixed with camphorated paramonochlorophenol)
      for 7 days, dentin powder from the infected specimens was obtained and assessed
      for bacterial quantity by spectrophotometry. It was found that calcium hydroxide
      mixed with camphorated paramonochlorophenol killed all of the Enterococcus
      faecalis inside the dentinal tubules. This result was better than that obtained
      with calcium hydroxide mixed with distilled water or with 0.2% chlorhexidine (p <
      0.05). Calcium hydroxide mixed with distilled water and calcium hydroxide mixed
      with 0.2% chlorhexidine were ineffective against these bacteria.

PMID- 11833680
TI  - The deterioration of rotary nickel-titanium files under controlled conditions.
AB  - It has been shown that rotary nickel-titanium files cannot be used indefinitely.
      Researchers and clinicians have not been able to agree on how many times a file
      can be used before being discarded, except if a file has fractured or become
      visibly distorted. This study used ISO size 20 files of 0.04 taper in the curved
      canals of extracted mandibular molars. The canals had been previously
      instrumented to an ISO size 15 with stainless steel hand files. The irrigant used
      during rotary and hand instrumentation was Glyde. The rotary files were closely
      examined with scanning electron microscopy before use to detect any defects. They
      were then reexamined after each of five uses to document deterioration. An
      electric handpiece was configured to rotate at 150 rpm and secured to the testing
      device, which also held the extracted tooth. The testing device controlled the
      load at 8 N, the depth of penetration for each canal and the rate of penetration
      (12 mm/min). Used instruments demonstrated surface fatigue wear and cracking.
      Torsional moment at failure was determined on a torsiometer for used and new
      instruments. Data (n = 10) were analyzed by analysis of variance. The torsional
      moment for used and new instruments was not affected by use (p = 0.25).

PMID- 11833681
TI  - A comparison of pain levels during pulpectomy, extractions, and restorative
      procedures.
AB  - Most previous studies on pain in endodontics have focused on pain that occurs
      after root canal therapy. Very few studies have compared pain during the root
      canal procedure with pain occurring during other dental procedures. In the
      present study, 250 patients were queried following dental procedures regarding
      their pain levels prior to treatment and their pain levels during the treatment
      procedure. Of the total number of patients, 150 had a pulpectomy, 50 patients had
      a single extraction, and 50 patients had a single restoration. These patients
      reported significantly more pain during extractions than during root canal
      therapy. Ninety-two percent of patients undergoing root canal therapy reported
      that pain during the procedure was less than or much less than anticipated.
      Eighty-three percent of the patients undergoing root canal therapy experienced
      less pain during the treatment procedure than they experienced prior to the
      treatment.

PMID- 11833682
TI  - Comparison of two ultrasonic instruments for post removal.
AB  - The relative performance of two different ultrasonic units commonly used
      clinically for post removal was evaluated using tips designed specifically for
      post vibration. Twenty-four extracted maxillary and mandibular cuspids with
      crowns removed at the labial cementoenamel junction were treated endodontically.
      Post spaces were made 10 mm into the roots before cementing a 16 mm #5 (0.050
      inch) Para-Post with zinc phosphate cement. The teeth were divided into three
      similar groups of eight. Post retention was assessed in group 1. Ultrasonic
      vibration was applied to groups 2 and 3 until post removal. The average force
      required to dislodge the posts from the teeth in group 1 (control group, no
      ultrasound) was 40.5 kg (SD = 12.3 kg). The average time for post removal in
      group 2 (Spartan) was 4:52 min (SD = 2:26). The average time for post removal in
      group 3 (Enac) was 1:31 min (SD = 0:34). The difference between groups 2 and 3
      was statistically significant (p < 0.005). Use of ultrasonic tips designed for
      post vibration and maximization of audible sound level during ultrasonic
      treatment of posts seem to play an important role in the effectiveness and
      efficiency of post removal. The results obtained indicate that both the Enac
      ultrasonic unit with the ST-09 vibration tip and the Spartan ultrasonic unit with
      the Analytic VT-S tip were effective. Nevertheless, the Enac ultrasonic unit with
      the ST-09 vibration tip was clearly more efficient under these study conditions,
      resulting in typical post removal times of <2 min.

PMID- 11833683
TI  - The ability of root ZX apex locator to reduce the frequency of overestimated
      radiographic working length.
AB  - The aim of this in vitro study was to evaluate the ability of the Root ZX device
      to avoid instrumentation beyond the apical foramen in premolars after
      conventional working length radiography. Thirty extracted premolars with 43 root
      canals were subjected to radiographic and electronic working length
      determination. Radiographic working length determination resulted in
      overestimation in 51% of the root canals, although the measuring file tip was
      located to be 0 to 2 mm short of the radiographic apex. Electronic working length
      measurements with the Root ZX reduced the percentage of overestimation to 21%. In
      6 root canals (14%), both radiographic and electronic working length measurements
      led to overestimation. It is concluded that complementing radiographic working
      length determination with electronic apex locator measurements may help to avoid
      overestimation beyond the apical foramen in premolars.

PMID- 11833684
TI  - Short-term evaluation of intentional replantation of vertically fractured roots
      reconstructed with dentin-bonded resin.
AB  - The purpose of this study was to evaluate intentional replantation of vertically
      fractured roots reconstructed with dentin-bonded resin. Twenty vertically
      fractured teeth were extracted intentionally and reconstructed with 4-META/MMA
      TBB dentin-bonded resin. After reconstruction, the teeth were replanted into the
      original sockets. The replanted teeth were evaluated by clinical criteria and
      radiographic examination. The observation periods ranged between 4 and 45 months.
      Longevity was calculated by the Kaplan-Meier method, and factors that had
      significant influence on the longevity were analyzed with the Log rank test at a
      95% level of confidence. From this short-term observation, 14 of 20 cases were
      functioned in the oral environment. Of these 14 cases, 6 could be considered
      truly successful and 8 cases needed further observation. The other six cases were
      total failures and were extracted. The longevity was calculated as 83.3% at 12
      months and 36.3% at 24 months. Teeth with thin roots or with longitudinal
      fractures extending over 2/3 of the root from the cervical portion toward the
      apex showed significantly lower longevity. It was concluded that this method had
      the potential to preserve vertically fractured teeth.

PMID- 11833685
TI  - Measurement of the distance between the minor foramen and the anatomic apex by
      digital and conventional radiography.
AB  - The purpose of this study was to determine the distance between the minor foramen
      and the anatomic apex from digital and conventional radiographs. Thirty permanent
      single-canal teeth with mature root apex were used. After access preparation, a K
      file was inserted into the canal until the tip of the file was just seen at the
      minor foramen under a x40 stereomicroscope. The file was fixed in the canal by
      filling the access with composite resin. The teeth with files in the canals were
      radiographed using a Schick CDR digital system and conventional radiography with
      E-speed film. For digital radiographs, the distance between the file tip and the
      center of radiographic apex was directly measured from the computer screen by
      using Schick CDR measurement software. For conventional radiographs, the distance
      was measured under a stereomicroscope at a magnification of x10 with a calibrated
      millimeter ruler. The mean distance was 0.494 mm measured from conventional
      radiographs and 0.594 mm from digital radiographs. These results agree with the
      current conception that endodontic working length should terminate 1 mm from the
      radiographic apex. There was a significant difference between the measurements on
      digital radiographs and those on conventional radiographs (p < 0.05, paired t
      test). However, the 0.1-mm difference has no clinical significance, because
      clinically, the working length is generally measured to the nearest 0.5 mm.

PMID- 11833686
TI  - Zebra XXIII, Part 2. Odontogenic fibroma.

PMID- 11833687
TI  - Maintaining scope of practice ensures continued success.

PMID- 11833688
TI  - Ki-67 expression in dentigerous cysts, unicystic ameloblastomas, and
      ameloblastomas arising from dental cysts.
AB  - This study investigated whether or not an ameloblastoma developing in the wall of
      a dentigerous cyst is a distinct lesion from the unicystic ameloblastoma. An
      immunohistochemical evaluation of Ki-67 in dentigerous cysts, unicystic
      ameloblastomas, and ameloblastomas arising in dentigerous cysts was done. The
      values of Ki-67 positivity were 3.14 for the dentigerous cyst, between 5.32 and
      16.56 for unicystic ameloblastoma, and 11.77 for ameloblastoma arising in a
      dentigerous cyst. Statistically significant differences were found between the
      dentigerous cyst and the unicystic ameloblastoma and between the dentigerous cyst
      and the ameloblastoma arising from a dentigerous cyst. No statistically
      significant difference was present between unicystic ameloblastoma and
      ameloblastoma arising from dentigerous cyst. These immunohistochemical data
      confirm the hypothesis that an ameloblastoma arising from a dentigerous cyst has
      a similar biological behavior to the unicystic ameloblastoma and should be
      considered as merely a histologic variant.

PMID- 11833689
TI  - Coronal microleakage of five materials used to create an intracoronal seal in
      endodontically treated teeth.
AB  - The purpose of this study was to quantitatively compare the sealing effectiveness
      of five restorative materials that were used to create an intracoronal double
      seal. Fifty-two extracted mandibular molars were randomly divided into five
      groups of 10 teeth, and one positive and one negative control tooth. The crowns
      were removed and the pulpal floor and canal orifices were sealed with 3 mm of one
      of the following materials: Amalgabond, C&B Metabond, One-Step Dentin Adhesive
      with AEliteflo composite, One-Step with Palfique composite, or intermediate
      restorative material (IRM). Each tooth was affixed to a fluid filtration device
      and the seal was evaluated at 0, 1, 7, 30, and 90 days. The results showed a
      significant (p = 0.0001) difference in leakage between the materials. At 7 days,
      IRM, AEliteflo, and Palfique leaked significantly more than Amalgabond or C&B
      Metabond. Amalgabond consistently produced the best seal of all the materials
      throughout the duration of the study.

PMID- 11833690
TI  - Effectiveness of intracanal irrigants and medications against the yeast Candida
      albicans.
AB  - An in vitro study was conducted to determine the susceptibility of the yeast
      Candida albicans to various intracanal irrigants and medications. The minimum
      inhibitory concentration (MIC) of sodium hypochlorite, hydrogen peroxide,
      chlorhexidine digluconate, and aqueous calcium hydroxide that is required to kill
      a standardized inoculum of C. albicans was determined. Growth of the yeast was
      measured by optical density. Sodium hypochlorite, hydrogen peroxide, and
      chlorhexidine digluconate were effective anticandidal agents with MICs of <10
      microgram/ml, 234 microgram/ml, and <0.63 microgram/ml, respectively. Aqueous
      calcium hydroxide had no activity. A standardized inoculum of C. albicans cells
      was also placed in direct contact with either calcium hydroxide paste or
      camphorated para-monochlorophenol (CPMC), and candidal growth was assessed by
      colony counts on Sabouraud's dextrose agar. Calcium hydroxide paste and CPMC,
      when maintained in direct contact with C. albicans, were effective antifungal
      agents.

PMID- 11833691
TI  - Vascular response of current and potential dental etchants.
AB  - This study investigated the hemostatic properties of current and potential dentin
      conditioners by observing the contraction of blood vessels using the rat carotid
      artery model. Four different agents (3M Scotchbond etchant, NRC, RC-Prep, File
      Eze) were used. Dose-dependent contractions/relaxations of the test materials
      were first compared with epinephrine, followed by administration of papaverine,
      which was used to reverse epinephrine-induced contractions. In all sequences, the
      contraction or relaxation forces produced by the test and control materials were
      recorded using a force displacement transducer. RC-Prep was the only agent to
      produce epinephrine-like contractions (vasoconstriction) in the rat carotid
      artery. No contraction could be achieved with 3M etchant. Dose-dependent
      relaxations were observed with 3M etchant, which eventually led to collapse of
      the vessel wall; afterward, no response could be achieved with administration of
      adrenalin. File-Eze and NRC also did not cause vasoconstriction. Both materials
      caused dose-dependent relaxations in the smooth muscle. However, subsequent
      administration of adrenalin and papaverine caused dose-dependent contractions and
      relaxations, respectively, showing that these etchant effects did not lead to
      collapse of the vessel wall, as did 3M etchant.

PMID- 11833692
TI  - Root surface temperature increase during Er:YAG laser irradiation of root canals.
AB  - The authors measured the temperature of the root surface during root canal
      preparation using Er:YAG laser irradiation and evaluated the thermal effect on
      the periodontal region. Twenty extracted human teeth with single roots were
      divided into two groups of 10. These were irradiated using an Er: YAG laser at 2
      Hz and 136 to 184 or 170 to 230 mJ/pulse for 1 min with a water spray. The
      temperature of the root surface was monitored using thermocouples throughout the
      procedure. The teeth were longitudinally bisected and observed by stereoscopy and
      scanning electron microscopy. The temperature on the root surface increased by
      less than 6 degrees C at the apical area and by less than 3 degrees C at the
      central area. A morphological evaluation revealed no carbonization or melting.
      These results suggest that the thermal effect on periodontal tissues during root
      canal preparation using an Er: YAG laser at less than 230 mJ/pulse for 1 min is
      minimal.

PMID- 11833693
TI  - The effects of eugenol and epoxy-resin on the strength of a hybrid composite
      resin.
AB  - The compatibility of different dental materials (root canal sealer and composite
      core build-up restoratives) is an important factor for a successful restoration.
      The aim of this in vitro study was to determine the effects on compressive and
      diametral tensile strength of a classical chemical cure composite resin (Henry
      Schein Composite Anterior-Posterior dental restorative) when in contact with
      either eugenol or an epoxy-resin (EZ-Fill) in a variety of situations: (a)
      eugenol or epoxy-resin added during mixing of a composite resin before curing;
      (b) vapor exposure to cured samples; and (c) specimens placed directly in eugenol
      or epoxy-resin (after curing). Compressive strengths and diametral tensile
      strengths were tested for each group. Only the addition of eugenol during mixing
      with the composite resin (directly before curing) resulted in specimens that were
      unable to be tested, because they did not achieve a full cure or hardness. For
      all other groups, there were no significant differences with respect to either
      compressive strength (p = 0.17) or diametral tensile strength (p = 0.39). Group 1
      (mixed directly with eugenol) was found to be statistically different from groups
      2 through 7.

PMID- 11833694
TI  - Influence of the canal contents on the electrical assisted determination of the
      length of root canals.
AB  - The purpose of this study was to compare the influence of the root canal status
      on the determination of the root canal length by an electronic apex locator in
      vital and necrotic canals and canals with root canal filling retrieval. One
      hundred seven teeth with a total of 171 canals with various contents (105 vital
      pulp, 47 necrotic pulp, and 19 retrieval of root canal filling materials) were
      measured for root canal length in vivo with the AFA Apex Finder. The distance
      between the file tip and the radiographic apex was also determined on
      radiographs. In 86% of the evaluated roots, the file tip position as indicated by
      the Apex Finder was located within 0.5 mm of a point 1.0-mm short of the
      radiographic apex. The Apex Finder showed higher accuracy for determining the
      apical constriction in vital canals (93.9%) than in necrotic canals (76.6%), and
      this difference was statistically significant (p < or = 0.05). The Apex Finder
      indicated the point -1 mm +/- 0.5 mm in canals with retrieval of root canal
      filling materials in 68.4% of these cases, but because of the small number of
      retrieval cases, this is not comparable statistically with vital and necrotic
      cases. The authors concluded that the AFA Apex Finder is highly accurate in vital
      canals.

PMID- 11833695
TI  - Comparison of the effectiveness of bacterial culture, 16S rDNA directed
      polymerase chain reaction, and checkerboard DNA-dNA hybridization for detection
      of Fusobacterium nucleatum in endodontic infections.
AB  - Fusobacterium nucleatum is a Gram-negative, non-spore-forming, nonmotile,
      obligatory anaerobic rod that is normally isolated from the oral cavity.
      Epidemiological studies have shown that this species is one of the most prevalent
      in primary root canal infections. The purpose of this study was to compare the
      effectiveness of bacteriological culture, 16S rDNA directed polymerase chain
      reaction and checkerboard DNA-DNA hybridization for detection of F. nucleatum
      strains in infected teeth associated with periradicular lesions. Thirteen single
      root teeth from adult patients, all having carious lesions, necrotic pulps, and
      radiographic evidence of periradicular bone loss were included in this study.
      Combining all methods, the results indicated that F. nucleatum was present in
      approximately 31% (4 of 13) of the specimens. Incidence of F. nucleatum in root
      canal infections, as evaluated in this study by polymerase chain reaction,
      culture, and DNA-DNA hybridization, was 15.4%, 15.4%, and 10.0%, respectively.
      Our data demonstrated that no method used herein could be considered superior for
      detecting F. nucleatum directly from clinical samples. However, the small number
      of samples examined and the low prevalence that was observed should be
      considered.

PMID- 11833697
TI  - Effect of calcium hydroxide on bacterial endotoxin in vivo.
AB  - The aim of this study was the histopathological evaluation of apical and
      periapical tissues in dog teeth that were submitted to bacterial endotoxin,
      associated or not with calcium hydroxide. After removal of the pulp from 60
      premolars, the teeth were divided into four groups and were filled with bacterial
      endotoxin (group 1), bacterial endotoxin plus calcium hydroxide (group 2), saline
      solution (group 3), or had induced periapical lesions with no treatment (group
      4). After 30 days, animals were killed and the teeth processed histologically.
      The inflammatory infiltrate, the thickness of the periodontal ligament, and the
      presence of resorption areas were similar for groups 1 and 4. Groups 2 and 3 were
      similar to each other. It can be concluded that the bacterial endotoxin caused a
      periapical lesion and that calcium hydroxide detoxified the lipopolysaccharides
      in vivo.

PMID- 11833696
TI  - Stimulation of matrix metalloproteinases by black-pigmented Bacteroides in human
      pulp and periodontal ligament cell cultures.
AB  - Matrix metalloproteinases (MMPs) are a group of proteolytic enzymes capable of
      degrading most components of the extracellular matrix. Recently, evidence has
      shown that MMPs may play a role in tissue degradation in inflamed dental pulp. To
      date very little is known regarding the mechanism of extracellular matrix
      destruction at the site of bacterial infection. The purpose of this study was to
      determine the effects of the supernatants from Porphyromonas endodontalis and
      Porphyromonas gingivalis on the production and secretion of MMPs by primary human
      pulp and periodontal ligament (PDL) cell cultures in vitro. The results were
      evaluated by substrate gel zymography from long-term cultures. The main
      gelatinase secreted by human pulp and PDL cells migrated at 72 kDa and
      represented MMP-2. Minor gelatinolytic bands were also observed at 92 kDa regions
      that correspond to MMP-9. After an 8-day culture period, P. endodontalis and P.
      gingivalis were found to elevate MMP-2 production both in human pulp and PDL cell
      cultures. In addition, the stimulation was in a dose- and time-dependent manner.
      Both human pulp and PDL cells, however, treated with either P. endodontalis or P.
      gingivalis had no effect on the pattern of MMP-9 produced or secreted in either
      cell extracts or conditioned medium fractions. These results indicate that black
      pigmented Bacteroides species play an important role in tissue destruction and
      disintegration of extracellular matrix in pulpal and periapical diseases. Thus,
      activation of MMPs may be one of the distinct host degradative pathways in the
      pathogenesis of microbial-induced pulpal and periapical lesion. An understanding
      of the actions of these black-pigmented Bacteroides species on pulp and PDL cells
      may result in new therapies to augment current treatment of pulpal and periapical
      lesions.

PMID- 11833698
TI  - Influence of calcium hydroxide dressing on the obturation of simulated lateral
      canals.
AB  - The purpose of this in vitro study was to evaluate what influence an
      interappointment dressing with calcium hydroxide might have on the ability to
      subsequently obturate simulated lateral canals. Twenty extracted single-rooted
      human teeth were instrumented at the working length to a #35 file before creating
      three simulated lateral canals on the mesial and distal surfaces of the root, one
      in each third, using a #15 engine reamer. After enlarging the root canals to a
      #45 file, the teeth were randomly divided into two groups of 10. In both groups
      AH26 was used as the sealer. In group A, the obturation was performed immediately
      using Ultrafil. In group B, root canals were filled with calcium hydroxide and
      incubated for 7 days. The teeth were then reinstrumented, irrigated with 2.5%
      sodium hypochlorite solution, dried with paper points, and obturated as in group
      A. Teeth in group A showed a larger number of filled lateral canals compared with
      those in group B. Statistical significant differences were observed when
      comparing the same third in the two groups (apical third p < 0.05, middle third p
      < 0.01, and coronal third p < 0.01). No differences were found among the
      different thirds in the same group (p > 0.05).

PMID- 11833699
TI  - The Novacor left ventricular assist system: clinical experience from the Novacor
      registry.
AB  - The electrically powered Novacor left ventricular assist (LVAS) system was first
      used clinically as a bridge to transplant in 1984. The configuration has evolved
      to the current wearable model used clinically for the first time in 1993. In
      1998, the inflow conduit was modified, reducing embolic events by 50%. Over 1100
      implants have been performed worldwide with cumulative support greater than 300
      patient years, and only 0.7% requiring replacement. The Novacor is a safe and
      effective device for bridge to transplant, bridge to recovery, or potentially
      permanent implant with reliable long-term support for periods as long as 4 years.

PMID- 11833700
TI  - Bridge to transplant with the HeartMate device.
AB  - The incidence and prevalence of chronic heart failure continues to increase, with
      an estimated 400,000 new cases per year in the United States. Cardiac
      transplantation is an effective therapy but is severely limited to approximately
      2300 patients per year due to the donor shortage. With ever increasing waiting
      times, a significant number of patients become severely debilitated or expire
      prior to transplantation. A mechanical circulatory support device was first used
      as a "bridge to transplantation" in 1969. Since then, mechanical devices have
      increased tremendously in reliability and efficaciousness. The HeartMate left
      ventricular assist device (LVAD) has been utilized extensively in a bridge to
      transplant application with excellent results. Patients refractory to aggressive
      medical management can be sustained reliably until transplantation. In addition,
      bridging allows for the correction of physiologic and metabolic dearrangements
      often seen in these severely ill patients prior to transplantation. Nutritional,
      economic, and quality-of-life issues also favor earlier LVAD placement in
      refractory patients. This reportsummarizes the overall bridging experience with
      the HeartMate LVAD and focuses on our experience with this device at Rush
      Presbyterian-St. Luke's Medical Center.

PMID- 11833701
TI  - Costs and insurance coverage associated with permanent mechanical cardiac
      assist/replacement devices in the United States.
AB  - Each year over 50,000 persons in the United States could potentially benefit from
      some form of permanent cardiac replacement or assistance. Approximately 7000 of
      these persons get on the waiting list for a transplant, and 2300 are
      transplanted. About 2000 patients are reportedly exposed to a mechanical cardiac
      assist device, most often as a bridge to transplant. The majority of persons who
      might benefit from cardiac replacement are never referred for treatment and,
      thus, the number of deaths on the waiting list is a misleading indicator of
      access to transplantation and overall patient mortality. The total economic
      burden associated with coronary artery disease and congestive heart failure now
      exceeds $140 billion each year, with approximately $700 million directly spent on
      heart transplant procedures alone. If a viable total artificial heart is devised
      to replace a failed heart, or a ventricular assist system to permanently assist a
      failing heart, direct aggregate expenditures alone are likely to be somewhere
      between $5.4 and $24.0 billion annually. Based on individual patient care costs,
      as well as aggregate national expenditures, insurers will be reluctant to pay for
      the permanent use of such devices, even though cost is reportedly not a
      consideration in coverage decisions. Today, medical benefits and added value are
      concepts that will shape the coverage determination process, as will increasingly
      liberal policies regarding payment for treatment costs in relationship to
      clinical trials. Nonetheless, resource allocation and rationing decisions loom
      large as strange "characters at play" on an international economic "stage," while
      being "directed" by worldwide health care needs.

PMID- 11833702
TI  - Left ventricular assist device as a bridge to recovery: present status.
AB  - A new application for left ventricular assist devices (LVAD) is as a bridge to
      recovery. In the settings of myocarditis and dilated cardiomyopathy, LVAD support
      is accompanied by marked hemodynamic, neurohormonal, physiologic, cellular, and
      molecular changes indicative of recovery. Despite these changes, experience with
      clinical successes is limited. Further studies of topics such as the timing of
      LVAD implantation and explantation, adjunct medical and surgical therapy, and
      optimum LVAD weaning protocols might help improve the success of this promising
      technology.

PMID- 11833703
TI  - Off-pump Coronary Artery Bypass Grafting in patients on chronic hemodialysis.
AB  - BACKGROUND: Off-pump Coronary Artery Bypass Grafting(CABG) has gained much
      support but has been scarcely reported in patients on chronic hemodialysis (HD).
      The details of CABG for such patients on chronic HD are presented. METHODS:
      Between January 1998 and December 1999, off-pump CABG was performed in 5 patients
      on chronic HD. All patients presented with unstable angina pectoris. The
      indication for off-pump CABG was suitable coronary anatomy (N = 5) and expected
      high risks associated with cardiopulmonary bypass due to reoperation (N = 1) and
      impaired cerebral blood flow (N = 2). The approach was median sternotomy (N = 4)
      and left anterior short thoracotomy (N = 1). The mean graft number was 2.0 +/-
      1.0 (range, 1-3). In situ arterial grafts were mainly used: the in situ left
      internal thoracic artery was used in four patients, the in situ right
      gastroepiploic artery in two, the in situ right internal thoracic artery in two,
      and the saphenous vein in two patients. RESULTS: There were no deaths or
      complications. Nine of 10 grafts were confirmed fully patent by postoperative
      angiography before hospital discharge. In a mean follow-up of 17.2 months, no
      patients had developed recurrence of angina or any cardiac symptom. CONCLUSION:
      Off-pump CABG using in situ arterial grafts can be performed on patients on
      chronic hemodialysis subject to suitable anatomy of the target coronary arteries.

PMID- 11833704
TI  - Simple de-airing technique for aortic valve replacement with upper
      ministernotomy.
AB  - Upper ministernotomy for aortic valve replacement is intimidating for many
      surgeons, not only for limited surgical exposure but also for the inability to
      complete de-airing the apex of the heart. Conversion to full sternotomy had been
      reported for this inability to de-air the apex of the heart in a limited number
      of cases. We describe a simple de-airing method by introducing a 16 GA catheter
      into the apex of the left ventricle through the aorta and prosthetic valve.

PMID- 11833705
TI  - Use of plasma exchange and heparin during cardiopulmonary bypass for a patient
      with heparin induced thrombocytopenia: a case report.
AB  - Patients with documented history of heparin-induced thrombocytopenia (HIT) pose a
      difficult problem during surgery using cardiopulmonary bypass (CPB). Several
      alternatives to heparin exist, but these products either are not approved for use
      in the United States or have more side effects than heparin. We report on a
      patient with documented heparin-induced antibody and left main coronary artery
      disease who underwent uneventful coronary artery bypass surgery and recovery by
      using preoperative plasmaphresis and limited use of porcine intestinal heparin
      during CPB.

PMID- 11833707
TI  - Fast track recovery of the cardiac surgical patient.

PMID- 11833706
TI  - Safety and efficacy of fast track in patients undergoing coronary artery bypass
      surgery.
AB  - BACKGROUND: The incidence of coronary artery bypass surgery has been increasing
      annually with increasing pressure on the health care system. Fast track has been
      proposed as a means to increase efficiency and volume, without an increase in
      hospital resources. To date this approach has not been critically assessed in
      Canada. METHODS: We examined 617 consecutive patients undergoing isolated CABG
      surgery. The patients were divided into (1) fast track (FT) recovery (n = 219),
      without admission to an ICU, and (2) non-fast track (NFT) recovery (n = 398) with
      direct admission to the ICU. There were no differences in age, gender, timing of
      surgery, left main stenosis, preoperative myocardial infarction, renal failure,
      diabetes, peripheral vascular disease, or in the incidence of chronic obstructive
      pulmonary disease between the two groups. The NFT group had a higher proportion
      of patients with NYHA Class III/IV symptoms preoperatively (65.7% vs. 57.3%, p =
      0.048), in patients with an ejection fraction < 40% (42.5% vs. 30.6%, p = 0.004),
      or in the number of individuals with an IABP inserted before surgery (13 vs. 1, p
      < 0.001). RESULTS: In the FT group the average period of aortic occlusion (40.7
      +/- 15.2 min vs. 71.8 +/- 26.5 min, p < 0.001) and perfusion time (67.8 +/- 24.5
      min vs. 117.5 +/- 40.2 min, p < 0.001) were significantly less than in the NFT
      group. The number of grafts per patient was 3.3 +/- 1.0 vs. 3.2 +/- 1.0,
      respectively (p = 0.38). Operative mortality was 0.9% in the FT group and 1.3% in
      the NFT group (p = 1.0). Significant differences were seen in the proportion of
      patients that suffered from postoperative ventilatory failure (3.2% in FT vs.
      12.1% in NFT, p < 0.001), and the proportion of patients that suffered any
      postoperative complication was significantly higher in the NFT group (21.4%) than
      in the FT group (9.1%, p < 0.001). The differences in postoperative complications
      resulted in a shorter length of stay (LOS) in FT patients (5.6 +/- 4.1 days vs.
      9.7 +/- 9.4 days NFT, p < 0.001). Only 4.1% of patients that entered the FT group
      failed and required admission to the ICU. Multivariate stepwise logistic
      regression analysis identified non-fast track recovery as an independent
      predictor of morbidity in CABG surgery patients. CONCLUSIONS: The data indicate
      it is possible to perform isolated CABG surgery, in a large proportion of the
      population, without the need for admission to an ICU for postoperative care.

PMID- 11833708
TI  - Late results of isolated mitral annuloplasty for "functional" ischemic mitral
      insufficiency.
AB  - BACKGROUND: Repair of functional ischemic mitral regurgitation (MR) due to
      annular deformity and leaflet restriction remains a challenge for the surgeon and
      lacks well-documented outcomes. We investigated outcomes in the treatment of
      functional ischemic MR corrected by annuloplasty techniques alone. METHODS: From
      May 1980 to July 1999, 174 patients underwent repair for functional ischemic
      mitral insufficiency with annuloplasty alone (128 ring annuloplasty; 46 suture
      annuloplasty). Acute insufficiency was present in 25 (14.4%). Concomitant
      procedures included CABG (n = 152; 87.4%). Patients were studied longitudinally
      with annual follow-up and echocardiograms. RESULTS: Overall hospital mortality
      was 17.8% and was increased by NYHA Class 4 (23.8% vs. 8.7%; p = 0.011), diabetes
      (25.0% vs. 13.6%; p = 0.059), and chronic mitral insufficiency (16.4% vs. 8.0%; p
      = 0.070). Multivariate analysis revealed age (beta = 0.099; p = 0.049) and
      ejection fraction < 30% (beta = 1.260; p = 0.097) as significant predictors of
      hospital death. Mean postoperative mitral insufficiency was 0.84 +/- 0.86 (scale
      of 0-4). NYHA Class 4 (beta = 2.33; p = 0.034) and simple suture annuloplasty
      (beta = 2.08; p = 0.07) were associated with increased risk of late cardiac
      death. Cumulative incidence of mitral reoperation was 7.7% at 5 years. At follow
      up, 89.7% of patients were in NYHA Class 1 or 2 with 83.4% having none or only
      mild mitral insufficiency. CONCLUSIONS: Ring annuloplasty is associated with a
      survival benefit when compared to simple suture repair in ischemic patients who
      require annuloplasty alone to correct the MR. Mitral reconstruction with a ring
      annuloplasty offers durable results in this homogeneous subset of functional
      ischemic MR patients. Ischemic mitral insufficiency is associated with
      significant late mortality.

PMID- 11833709
TI  - "Single suture" for exposure of the heart in left ventricular assist device
      placement.
AB  - Using the "single suture" technique described for exposure of the heart during
      off-pump coronary surgery, all surfaces of the heart may be exposed with little
      hemodynamic compromise. Using this technique, the apex of the heart is easily
      elevated for left ventricular assist device (LVAD) insertion in patients with
      either ischemic or dilated cardiomyopathy. This technique may provide the
      groundwork for routine placement of LVADs without the use of cardiopulmonary
      bypass.

PMID- 11833710
TI  - Cardiac papillary fibroelastoma on the mitral valve.

PMID- 11833711
TI  - Mid-term results of the Ross procedure.
AB  - Although the Ross procedure has been performed for over three decades, its role
      in the management of patients with aortic valve disease is not well established.
      This study reviews our experience with this operation. From 1990 to 1999, 155
      patients underwent the Ross procedure. The mean age of 106 men and 49 women was
      35 years. Most patients (85%) had congenital aortic valve disease. The pulmonary
      autograft was implanted in the subcoronary position in 2 patients, as an aortic
      root inclusion in 78, and aortic root replacement in 75. The follow-up extended
      from 9 to 114 months, mean of 45 +/- 28 months, and it was complete. All patients
      have had Doppler echocardiographic studies. There was only one operative and one
      late death. The survival was 98% at 7 years. The freedom from 3+ or 4+ aortic
      insufficiency was 86% at 7 years and the freedom from reoperation on the
      pulmonary autograft was 95% at 7 years. Dilation of the aortic annulus and/or
      sinotubular junction was the most common cause of aortic insufficiency. One
      patient required three reoperations on the biological pulmonary valve. Most
      patients (96%) have no cardiac symptoms. The Ross procedure has provided
      excellent functional results in most patients, but progressive aortic
      insufficiency due to dilation of the aortic annulus and/or sinotubular junction
      is a potential problem in a number of patients.

PMID- 11833712
TI  - The administration of lipopolysaccharide, in vivo, induces alteration in L
      leucine intestinal absorption.
AB  - The objective of the present study was to determine the alterations in L-leucine
      intestinal uptake by intravenous administration of Lipopolysaccharide (LPS),
      which is a constituent of gram negative bacterial, causative agent of sepsis. The
      amino acid absorption in LPS treated rabbits was reduced compared to the control
      animals. The LPS effect on the amino acid uptake was due to an inhibition of the
      Na+-dependent system of transport, through both reduction of the apparent
      capacity transport (Vmax) and diminution of the Na+/K-ATPase activity. The
      results have also shown that the LPS decreases the mucosal to serosal
      transepithelial flux and the transport across brush border membrane vesicles of L
      leucine. The study of possible intracellular mechanisms implicated in the LPS
      effect, showed that the second messengers calcium, protein kinase C and c-AMP did
      not play any role in this effect. However, the absence of ion chloride in the
      incubation medium removes the LPS inhibition and the intracellular tissue water
      was affected by the LPS treatment. Therefore, the inhibition in the L-leucine
      intestinal absorption, by intravenous administration of LPS, could be mainly
      produced by the secretagogue action of this endotoxin on the gut.

PMID- 11833713
TI  - Structure-function relationships of human apolipoprotein D an immunochemical
      analysis.
AB  - Apolipoprotein D (apoD), a 169 amino acid member of the lipocalin family, is
      thought to be a transporter of small, hydrophobic ligands. A panel of 10 anti
      apoD monoclonal antibodies (mAbs) was prepared and characterized in order to
      define apoD structure-function relationships. An apoD epitope map was constructed
      based on reactivity of the mAbs with apoD fragments. Three mAbs react with
      epitopes between apoD residues 7-78, seven mAbs with epitopes between residues
      128-169, one mAb recognizes an epitope that straddles residues 99-102 and one mAb
      is specific for an epitope composed of non-contiguous apoD residues. Several
      pairs of mAbs whose respective epitopes are widely separated in apoD primary
      structure can compete for binding to immobilized apoD. This would be consistent
      with the compact beta-barrel tertiary structure that apoD is thought to adopt.
      None of the mAbs block the interaction of apoD with pregnenolone, a putative
      physiological ligand for apoD.

PMID- 11833714
TI  - Inhibition of type A monoamine oxidase by coptisine in mouse brain.
AB  - The inhibitory effects of coptisine, a protoberberine isoquinoline alkaloid, on
      type A and type B monoamine oxidase (MAO-A and MAO-B) activities in mouse brain
      were investigated. Coptisine showed an inhibitory effect on MAO-A activity in a
      concentration-dependent manner using a substrate kynuramine, but coptisine did
      not inhibit MAO-B activity. Coptisine exhibited 54.3% inhibition of MAO-A
      activity at 2 microM. The values of Km and Vmax of MAO-A were 151.9 +/- 0.6
      microM and 0.40 +/- 0.03 nmol/min/mg protein, respectively (n=5). Coptisine
      competitively inhibited MAO-A activity with kynuramine. The Ki value of coptisine
      was 3.3 microM. The inhibition of MAO-A by coptisine was found to be reversible
      by dialysis of the incubation mixture. These results suggest that coptisine is a
      potent reversible inhibitor of MAO-A, and that coptisine functions to regulate
      the catecholamine content.

PMID- 11833715
TI  - Brain receptor binding characteristics and pharmacokinetic-pharmacodynamic
      analysis of thyrotropin-releasing hormone analogues.
AB  - Thyrotropin-releasing hormone (TRH) receptor binding in the rat brain after
      intravenous (i.v.) injections of novel TRH analogues, taltirelin and montirelin,
      was examined and the data were analyzed in relation to their plasma
      concentrations which were simultaneously determined. Taltirelin and montirelin
      inhibited specific [3H]-Me-TRH binding in the rat brain and their Ki values were
      311 and 35.2 nM, respectively. The i.v. injection of taltirelin and montirelin
      (0.1-3 mg/kg) produced a significant reduction in [3H]-Me-TRH binding sites (Bmax
      values) in the rat brain. The reduction by both agents tended to reach a maximum
      after 60 min and lasted up to at least 120 min. On the other hand, the i.v.
      injection of both agents had little significant effect on the apparent
      dissociation constant (Kd) for [3H]-Me-TRH in the rat brain. Plasma
      concentrations of taltirelin and montirelin in rats peaked immediately after i.v.
      injection, and thereafter they decreased with t 1/2 of 23.0 and 14.1 min,
      respectively. Counter-clockwise hysteresis between the plasma concentration and
      receptor occupancy of these agents was observed after the i.v. injection of
      taltirelin and montirelin, and the temporal delay between plasma concentration
      and brain receptor occupancy was successfully minimized using the "effect
      compartment" model in combination with the "linear-effect" model. We concluded
      that taltirelin and montirelin exert a fairly potent effect following sustained
      occupation of brain TRH receptors under in vivo condition. Thus, both agents
      could be clinically useful for the treatment of CNS disorders.

PMID- 11833716
TI  - Localization of metallothionein I-II immunoreactivity in bovine pituitary gland.
AB  - Metallothioneins belong to a family of shock proteins characterized by an unusual
      high content of cystein, absence of aromatic amino acids and high metal content
      (Zinc and Copper). Metallothioneins are ubiquitously present in a large variety
      of prokaryotic and eukaryotic species as well as in all mammalian organs and
      tissues examined thus far. To the best of our knowledge this is the first report
      describing the presence of metallothioneins in the pituitary gland.
      Metallothioneins were identified immunohistochemically and chromatographically
      both in the neuro and adenohypophysis of the bovine pituitary gland.
      Metallothioneins are highly expressed in the neurohypophyseal glial cells, and in
      a subpopulation of folliculo-stellate cells located in the pars intermedia of the
      adenohypophysis. While the specific role of these proteins in the pituitary gland
      remains to be established, we hypothesize that, besides their protective action
      against free radicals, hypophyseal metallothioneins might be involved in the
      regulation of metal ion homeostasis with putative implication in release of
      hypothalamic peptide hormones in the neurohypophysis and synthesis/release of
      alpha-MSH by POMC-cells located in the pars intermedia of the adenohypophysis.

PMID- 11833717
TI  - The preventive effects of G115 on balloon injury-induced neointima formation in
      rats.
AB  - After percutaneous transluminal coronary angioplasty (PTCA), 30-50% of the
      patients may present with restenosis within 6 months. The aim of this study was
      to search for a preventive remedy against the balloon injury-induced neointima
      formation. Ginseng, with its wide indications on immune and cardiovascular
      functions, has prompted us to explore its role in neointima formation. In the
      present study, we aimed to explore if a standardized Panax Ginseng extract G115
      was able to inhibit neointimal formation. With BrdU luminencence assay, maximal
      proliferation of rat smooth muscle cells was reduced to 24% of control values by
      G115. Norepinephrine-induced vasocontraction was antagonized in 21% and 44% by
      1.44mg/ml and 2.88mg/ml of G115, respectively. Neointima-to-lumen area ratio of
      balloon-injured rat carotid arteries was reduced 77.3% by G115 as compared to the
      sham control. These results demonstrate the preventive effects of ginsenosides on
      angioplasty-mediated neointima formation.

PMID- 11833718
TI  - The contributions of plasma membrane Na+-Ca2+-exchange and the Ca2+-ATPase to the
      regulation of cytosolic calcium ([Ca2+]i) in a clonal pituitary cell line (AtT
      20) of mouse corticotropes.
AB  - Single cell calcium microfluorimetry was used to examine the regulation of
      [Ca2+]i homeostasis in a clonal cell line of corticotropes (AtT-20 cells). Single
      cells, loaded with fura-2/AM, were exposed briefly to elevated potassium chloride
      (KCI, 40 mM, 5 sec). The time constant of decay of the [Ca2+]i signal was used as
      an index of [Ca2+]i extrusion and/or sequestration. Substitution of extracellular
      sodium with lithium, N-methyl-D-glucamine (NMDG), or Tris, increased resting
      levels of [Ca2+]i and significantly increased the time constant of [Ca2+]i decay
      by 40% compared to control indicating the participation of Na+-Ca2+-exchange.
      Prior exposure of single cells to thapsigargin (1 microM) or BuBHQ (10 microM).
      inhibitors of the SERCA Ca2+-ATPases, and/or the mitochondrial uncoupler FCCP (1
      microM) did not significantly change the time constant of [Ca2+]i decay following
      KCl. Lanthanum ions (La3+), applied during the decay of the KCI-induced increase
      in [Ca2+]i, significantly increased the time constant of the return of [Ca2+]i to
      resting levels by 70% compared to control. Brief exposure of cells to sodium
      orthovanadate, an inhibitor of ATP-dependent pump activity, slowed and longer
      exposures prevented, the return of [Ca2+]i to resting levels. We conclude that
      neither intracellular SERCA pumps nor mitochondrial uptake contribute
      significantly to [Ca2+]i sequestration following a [Ca2+]i load and that the
      plasma membrane Ca2+-ATPase contributes to a greater extent than the Na+-Ca2+
      exchanger to the return of [Ca2+]i to resting levels following a [Ca2+]i load
      under these experimental conditions.

PMID- 11833719
TI  - Mechanisms involved in the relaxation of bovine aortic endothelial cells.
AB  - The importance of endothelial cell contraction in the regulation of vascular
      biology is being increasingly recognized. Our group has demonstrated that
      reactive oxygen species, particularly hydrogen peroxide, which are released in
      pathological conditions such as ischemia-reperfusion, are able to induce
      contraction in bovine aortic endothelial cells (BAEC). The cGMP-dependent
      relaxation of contractile cells depends on the ability of the cyclic nucleotide
      to interfere with intracellular calcium; however, this is not the only mechanism
      involved. The present experiments were designed to analyse the mechanism by which
      cGMP induces relaxation in BAEC. Sodium nitroprusside (SNP), an activator of
      soluble guanylate cyclase, as well as atrial natriuretic (ANP) and C-type
      natriuretic (CNP) peptides, activators of particulate guanylate cyclase, blunted
      the hydrogen peroxide-induced contraction of BAEC and myosin light chain
      phosphorylation. The inhibitory effect was more marked with SNP and CNP than with
      ANP, and the action of SNP and CNP were partially reversed by blocking soluble
      and particulate guanylate cyclases, respectively. Dibutyryl cGMP (db-cGMP), a
      cGMP analogue, mimicked the effect of SNP and CNP. Cyclic GMP-dependent protein
      kinase (cGK) protein levels and activity were measured. Hydrogen peroxide induced
      a significant reduction in cGK activity without any change in protein level. This
      effect was completely reversed by preincubation with db-cGMP. Calyculin A, a
      myosin light chain phosphatase inhibitor, prevented the cGMP-induced relaxation
      of BAEC. SNP, CNP and db-cGMP also partially prevented the hydrogen peroxide
      induced increase in intracellular calcium levels. Catalase completely blocked
      this effect. In summary, the present results support a role for those metabolites
      which activate guanylate cyclases in the relaxation of BAEC, and suggest that the
      cGMP-induced BAEC relaxation could be due, at least partially, to the stimulation
      of cGK and/or myosin light chain phosphatase activity, and to calcium blockade.

PMID- 11833720
TI  - Involvement of Ca2+ waves in excitation-contraction coupling of rat atrial
      cardiomyocytes.
AB  - Two-dimensional and line-scan analyses of the early phase Ca2+ transients in rat
      cardiomyocytes were performed with a rapid-scanning laser confocal microscope and
      fluo-3 to elucidate the mechanism of activation of Ca2+ release from the
      sarcoplasmic reticulum in atrial myocytes which lack a well developed T-tubular
      network. On electrical stimulation of ventricular myocytes, Ca2+ concentration
      began to rise earliest at the Z-line level and became uniform throughout the
      cytoplasm within about 10 msec. In contrast, on stimulation of atrial myocytes,
      the earliest rise in Ca2+ occurred at the cell periphery and then spread to the
      cell interior; cytoplasmic Ca2+ became uniform after more than 30msec. The
      velocity of the propagation of rise in Ca2+ was 112 +/- 5.1 microm/sec (n = 10),
      which was similar to that of spontaneous Ca2+ waves observed in atrial and
      ventricular myocytes. No difference in frequency, amplitude and kinetics of
      spontaneous Ca2+ sparks was observed between the subsarcolemmal and central
      regions of atrial myocytes. Ryanodine concentration-dependently decreased the
      contractile force of isolated rat atrial and ventricular tissue preparations; the
      sensitivity was higher in atrial myocytes. The present study visualized the
      involvement of a propagated Ca2+-induced-Ca+ release mechanism in atrial but not
      ventricular myocytes. This difference may underlie some of the atrioventricular
      difference in response to physiological and pharmacological stimuli.

PMID- 11833721
TI  - Pharmacokinetic studies of methionine in rats using deuterium-labeled methionine
      quantitative assessment of remethylation.
AB  - The pharmacokinetics of methionine has been studied in rats by means of stable
      isotope methodology. After the i.v. bolus injection of [2H7]methionine (5 mg/kg
      body wt.), the plasma concentrations of [2H7]methionine, demethylated
      [2H4]homocysteine and remethylated [2H4]methionine were determined simultaneously
      with endogenous methionine and homocysteine by gas chromatography-mass
      spectrometry. The half-life for [2H7]methionine were 35.0 +/- 6.9 min. The
      appearance of the metabolites, [2H4]homocysteine and [2H4]methionine, in the
      plasma was very rapid. The fraction of [2H7]methionine that remethylated to
      [2H4]methionine through [2H4]homocysteine were 0.185 +/- 0.028. The administered
      [2H7]methionine did not influence the plasma levels of endogenous methionine and
      homocysteine. The present stable isotope methodology has made it possible to
      evaluate the pharmacokinetics of methionine, including the estimation of
      remethylation.

PMID- 11833722
TI  - Feasibility of waste stabilization pond technology for small municipalities in
      Colombia.
AB  - The selection of any wastewater treatment technology should take into
      consideration both "software" and "hardware" aspects. There are contrasting
      opinions regarding the feasibility of waste stabilisation ponds (WSP): some
      emphasise their advantages while others are concerned with their high land area
      requirements. As with any technology, WSP are feasible under specific
      circumstances related to the context where they are to be implemented. In this
      study data were collected from three regions in Colombia (Narino, Tolima and
      Valle del Cauca) in order to assess the feasibility of WSP under real conditions
      in a tropical country. A feasibility matrix was developed in order to organise
      and synthesise the information gathered. The results obtained showed that WSP are
      highly feasible in Tolima and Valle del Cauca due to the fact that these regions
      have geographical, socio-economic and technical characteristics that enhance the
      advantages of WSP technology. Narino has a very mountainous topography along with
      other local limitations that hinder the application of WSP technology. The cost
      of land was not found to be a real limitation for the technology, whereas the
      availability of land is. Finally, the feasibility matrix may be a good planning
      tool at regional or national levels in order to help decision-making regarding
      cost-effective wastewater treatment alternatives on the basis of local
      conditions.

PMID- 11833723
TI  - The potential for water hyacinth to improve the quality of Bogota River water in
      the Muna Reservoir: comparison with the performance of waste stabilization ponds.
AB  - The potential application of Water Hyacinth (Eichhornia crassipes) in organic
      matter degradation, sedimentation, nutrient and heavy metal absorption and sulfur
      reduction in the Muna Reservoir has been tested in experimental lagoons. The
      lagoons were operated at hydraulic retention times (HRT) of 6, 9 and 15 days. One
      lagoon was covered with Water Hyacinth, which is naturally growing in the Muna
      Reservoir, while another lagoon was operated as a conventional oxidation pond.
      The Water Hyacinth lagoon had better removal efficiencies for almost all
      parameters measured: BOD5, total suspended solids, COD, nitrogen, phosphorus and
      heavy metals. The oxidation lagoon was facultative for HRT of 9 and 15 days, and
      anoxic when operated at 6 days HRT. At HRT of 15 days the water quality in the
      effluent of the covered lagoon corresponded to 12 mg/l of BOD, 6 mg/l of
      suspended solids and 0.8 mg/l of hydrogen sulfide. Hydrogen sulfide levels in the
      Muna reservoir can be substantially reduced at HRT higher than 15 days in both
      lagoons. The uncovered lagoon had better hydrogen sulfide removal during the day
      but presents high levels at night. If the hydraulic retention time in the Muna
      reservoir is increased, the water quality of the Bogota river can be
      substantially improved for all the HRTs tested in the pilot units. HRT seems to
      give a better prediction of overall effluent water quality than surface loading.
      More research is needed in order to define the optimum water hyacinth density in
      the Muna reservoir to determine its influence on the water quality of the
      effluent. The influence is expected to be negative due to an internal increase of
      BOD, solids, nutrients and metals loads due to plant decay.

PMID- 11833724
TI  - Comparison of conventional and macrophyte-based systems for the treatment of
      domestic wastewater.
AB  - Different wetland and stabilisation ponds, comprising of duckweed, reed and algal
      systems, were compared for the treatment of domestic sewage. Within the large
      performance variations observed within systems, the differences observed between
      systems can be considered to be insignificant.

PMID- 11833725
TI  - Low cost reclamation using the Advanced Integrated Wastewater Pond Systems
      Technology and reverse osmosis.
AB  - The sustainability of wastewater reclamation and reuse schemes is often limited
      by the increase in salt concentration that occurs with each water use. In this
      pilot study, we show that the cost of reclaiming wastewater and removing salt can
      be dramatically decreased by integrating recent advances in wastewater pond
      design, solids separation equipment, and membrane technology. Effluent from an
      AIWPS Facility was clarified in a Krofta Supracell Dissolved Air Flotation (DAF)
      unit and a Slow Sand Filter (SSF) prior to final treatment in an Expertise S.r.l.
      reverse osmosis (RO) unit. The ponds of the AIWPS Facility removed an average of
      82% of soluble BOD and 80% of soluble nitrogen. Following clarification,
      filtration, and RO treatment, the pollutant removals were > 99% for soluble BOD,
      > 99% for soluble nitrogen, and 98% for TDS. Based on membrane fouling rate data,
      the cleaning interval for the RO membranes in a full-scale AIWPS-RO Facility
      would be over 100 days. This interval is on par with that typically seen in full
      scale reclamation facilities treating secondary activated sludge effluent with
      microfiltration prior to reverse osmosis. A 4-MLD AIWPS-RO Facility is expected
      to produce permeate water at substantially lower cost and lower energy
      consumption (US $698 and 443 kWh per million liters treated) than a system of
      equal capacity using conventional activated sludge secondary treatment followed
      by microfiltration and reverse osmosis (US $1274 and 911 kWh per million litres
      treated). This cost and energy differential is attributable to the lower capital
      and operating expenses of the AIWPS Technology in comparison with activated
      sludge.

PMID- 11833726
TI  - Domestic wastewater treatment in waste stabilization ponds for irrigation in
      Mendoza, Argentina: policies and challenges.
AB  - Arid areas call for imaginative water management solutions to avoid the dangers
      of water shortages. Growing demands of water for domestic and industrial uses
      decrease the availability of water for agriculture. It therefore becomes
      necessary to set up a policy for the use of domestic effluents. For the province
      of Mendoza, Argentina, with 1,500,000 inhabitants, a master plan was designed as
      of 1991 for the treatment of domestic effluents and subsequent disposal for
      irrigation. The guidelines set up by WHO for the use of wastewater in
      agricultural applications were taken into consideration. At present, the Province
      of Mendoza has available projects which are either complete, in execution or in
      the bidding process, entailing secondary treatment capacity with reuse of 320,000
      cubic metres/day and an estimated possible irrigation area of 10,000 hectares.
      With this infrastructure, some strategic lines of action are recommended to
      establish a policy for the agricultural use of wastewater: (a) to program the use
      of treated wastewater to avoid discharges to irrigation flows; (b) to develop an
      institutional scheme for the efficient and safe use of these waters; and (c)
      develop scientific and technologic know-how to accompany the updated policies.

PMID- 11833727
TI  - Effects on crops of irrigation with treated municipal wastewaters.
AB  - The fertilizing potential of treated municipal wastewater (oxidation ditch) and
      crop sanitary acceptability for direct human consumption were evaluated in
      Mendoza, Argentina. Two experiments were performed on a pilot plot planted with
      garlic (1998) and onions (1999) using furrow irrigation with three types of water
      in 10 random blocks: treated effluent (2.5 x 10(3) MPN Escherichia coli/100 ml, 3
      helminth eggs/l, and Salmonella (positive); and well water (free of
      microorganisms), with and without fertilizer. Two responses were evaluated: (1)
      crop yield, and (2) crop microbiological quality for human consumption at
      different times after harvest. Crop yields were compared using Variance analysis.
      Crops' sanitary acceptability was assessed using a two-class sampling program for
      Salmonella (n=10; c=0), and a three-class program for E. coli (n=5, c=2, M=10(3)
      and m=10 MPN/g) as proposed by the International Commission on Microbiological
      Specifications for Foods (ICMSF) for fresh vegetables. Wastewater irrigation
      acted as well water with fertilizer, increasing garlic and onion yields by 10%
      and 15%, respectively, compared to irrigation with well water with no fertilizer.
      Wastewater-irrigated garlic reached sanitary acceptability 90 days after harvest,
      once attached roots and soil were removed. Onions, which were cleaned immediately
      after harvest, met this qualification earlier than garlic (55 days). Neither the
      wastewater-irrigated crops nor the control crops were microbiologically
      acceptable for consumption raw at harvest.

PMID- 11833728
TI  - Microbiological quality of a waste stabilization pond effluent used for
      restricted irrigation in Valle Del Cauca, Colombia.
AB  - This paper discusses the applicability of effluent reuse in agriculture after
      treatment in a series of anaerobic, facultative and maturation ponds. The WSP
      system is located in Ginebra municipality, a small town in southwest Colombia.
      The total HRT is 12 days. Several samples of the final effluent were taken over a
      55 day period and were analysed for E. coli, Streptococcus spp. and helminth
      eggs. Some additional grab samples were taken to determine the presence of
      pathogenic bacteria such as Salmonella spp. and Shigella spp. The results showed
      that the system was able to remove 4 log units of E. coli, 1 log unit of
      Streptococcus spp. and 100% of helminth eggs. Meanwhile, Salmonella spp. were
      detected in the effluent of the facultative pond whilst Shigella spp. were not
      detected in any sample. The main species of helminth eggs encountered were Taenia
      spp., Ascaris spp., Trichuris spp., Hymenolepis nana, H. diminuta and Enterobius
      vermicularis. Removal efficiencies were satisfactory despite the relatively short
      HRT. Nevertheless, WHO guidelines were slightly surpassed in the case of E. coli
      for unrestricted irrigation. The helminth egg value was always below the maximum
      WHO limit. Hence, this effluent can be safely used for restricted irrigation
      provided that field workers are protected from direct contact with wastewater
      given the presence of Salmonella spp. in the facultative pond effluent.

PMID- 11833729
TI  - Relationship between first-order decay coefficients in ponds, for plug flow, CSTR
      and dispersed flow regimes.
AB  - Adequate consideration of the hydraulic regime of a pond is essential in the
      analysis of BOD and coliform removal, and considerable divergence exists in the
      literature when reporting removal coefficients. This paper aims at integrating
      the existing approaches, by quantifying the relationship between the first-order
      removal coefficients K from the three main hydraulic regimes (CSTR, plug flow and
      dispersed flow) adopted in the design and performance evaluation of ponds. Based
      on theoretical considerations and statistical regression analyses, the
      relationship between the K values is investigated, quantified and modelled. Two
      tables are presented and two equations are proposed, which allow conversion of K
      values obtained for dispersed flow to (a) K for CSTR and (b) K for plug flow,
      based on the hydraulic detention time t and the dispersion number d. These
      coefficients, when applied in the CSTR or plug-flow equations, will give
      approximately the same prediction of the effluent concentration as that obtained
      when using the dispersed-flow model with its proper coefficient. With this
      approach designers can apply, and researchers can report, K values for the two
      idealised flow patterns (CSTR and plug flow).

PMID- 11833731
TI  - The influence of thermal stratification on the hydraulic behavior of waste
      stabilization ponds.
AB  - Thermal stratification, which is characterized by a high vertical thermal
      gradient, is usually observed in deep lakes. However, although waste
      stabilization ponds have small depths, their high turbidity provides favorable
      conditions for the occurrence of this phenomenon, mainly during summer. During
      that time of the year, the layers nearest to the surface concentrate a larger
      amount of thermal energy compared to the deeper layers, which results in a
      temperature difference between the surface and the bottom of the pond. As a
      consequence a density profile appears, with the less dense layers located at the
      surface of the pond and the densest ones close to the bottom. This stratification
      in the water column induces alterations in the flow pattern and a decrease of the
      useful volume of the pond. This paper presents a mathematical model developed to
      forecast the conditions of thermal stratification in waste stabilization ponds
      and the volume actually used for wastewater treatment. With these values it is
      possible to correct the average residence time of the liquid in the pond. The
      theoretical results were compared with experimental observations, and maximum
      differences of 15% between the calculated and observed temperature profiles were
      found.

PMID- 11833730
TI  - Compartmental model for organic matter digestion in facultative ponds.
AB  - A model has been developed for the digestion of organic matter in facultative
      ponds in tropical regions. Complete mixing has been assumed for the aerobic and
      anaerobic compartments. Settling, aerobic layer oxidation, and anaerobic layer
      methanogenesis are the main processes for organic matter removal in the water
      column. Exchange processes between layers are dispersive or soluble exchange,
      solubilization and transport of organic matter from sediments to water column are
      also taken into account. Degradation of organic matter in the sediments produces
      gaseous emissions to the water column. The exchange between bubbles ascending and
      the water column was measured. The model was calibrated with data obtained from a
      pilot facultative pond built in Muna Reservoir in Bogota. The pond was sampled
      during 4 months to compare data between its water hyacinth covered section and
      uncovered section. The results clearly show the relative importance of different
      BOD removal processes in facultative ponds and suggest modifications to further
      improve performance. The results from the model suggest that internal loadings to
      facultative ponds due to solubilization and return of organic matter from the
      sediments to the aerobic layer greatly influence the soluble BOD effluent
      concentration. Aerobic degradation activity in the facultative pond does not
      affect significantly the effluent concentration. Anaerobic degradation activity
      in the facultative pond can more easily achieve increases in the removal
      efficiencies of BOD.

PMID- 11833732
TI  - Removal of bacterial and viral faecal indicator organisms in a waste
      stabilization pond system in Choconta, Cundinamarca (Colombia).
AB  - A major objective for domestic wastewater treatment using waste stabilization
      pond systems is the removal of pathogenic microorganisms. Traditional evaluation
      parameters for faecal contamination are the total and faecal coliforms. However,
      epidemiological studies, environmental resistance and the behaviour in the
      treatment systems, show that viruses are an important disease agent and even more
      resistant to disinfection than bacteria. Therefore, it is important to introduce
      viruses as a faecal indicator and to compare them with the traditional bacterial
      indicators. A waste stabilization pond system was evaluated in the municipality
      of Choconta, Cundinamarca (Colombia), for the removal of faecal indicators (such
      as Escherichia coli, Streptococcus faecalis, Clostridium perfringens) and viruses
      like F+, somatic and Bacteroides fragilis phages. The system includes two
      facultative ponds in series with a flow of 1555 m3/day. Samples were collected at
      the entrance of the system, in the two ponds and from the final effluent. Results
      show a decrease between 0.3 and 4.7 logarithmic units in the bacterial indicators
      and between 1 and 4.6 logarithmic units with viral indicators.

PMID- 11833733
TI  - The effect of pH on enterococci removal in Pistia-, duckweed- and algae-based
      stabilization ponds for domestic wastewater treatment.
AB  - A batch scale experiment was conducted to determine the effect of pH on
      enterococci die-off. A continuous flow system was also established to determine
      the environmental conditions and their effects on enterococci removal. The batch
      experiment was conducted for pHs: 4, 5, 7, 9, and 11 under light and dark
      conditions. Enterococci and DO were measured every day and every other day
      respectively for nine days. Pathogen removal rates at pH 4, 5, 7, 9 and 11 in the
      light/dark were (expressed as d(-1)) -2.1/-2.1, -2.1/-1.5, -2.1/-1.5, -2.1/-1.4
      and -1.1/-1.0, respectively. DO levels were low, between 0.17 mg/L at pH 4
      (light) to 0.56 mg/L at pH 7 (light). The continuous flow system consisted of
      Pistia (water lettuce), duckweed and algal treatments in series of four ponds
      with a total retention period of 28 days after two days of anaerobic pre
      treatment. After two months of operation, temperature, pH, DO, TDS, and
      enterococci populations were monitored. A low pH of 4.4 was obtained in the
      Pistia ponds. Neutral conditions were observed in the duckweed system, while pH
      values >9 were observed in the algal system. Enterococci decreased from 7.8 x
      10(6) to <500/100 ml in all treatment systems after 28 days of treatment with no
      significant differences between treatments.

PMID- 11833734
TI  - Sludge accumulation in polishing ponds treating anaerobically digested
      wastewater.
AB  - When ponds are used for wastewater treatment, settleable solids will form a
      steadily growing bottom sludge layer, which reduces their effective volume.
      Eventually this sludge must be removed to ensure that the pond maintains the
      required retention time to keep performing properly. The settleable solids may
      either be present in the influent or they are formed during the treatment as a
      result of algal flocculation. An experimental investigation was carried out to
      evaluate bottom sludge accumulation in a polishing pond used for treatment of
      UASB effluent. The mass and composition of the bottom sludge formed in a
      polishing pond was evaluated after the pilot scale pond had been in operation for
      1 year and about 60 m3 of digested wastewater had been treated per m3 of pond.
      The bottom sludge mass represented a solids accumulation of 70 g per m3 of
      digested wastewater. About half of these solids were the result of settling of
      influent solids in the first part of the pond, while the other half was
      attributable to settling of algae, formed in the pond. It is concluded that the
      bottom sludge growth in a polishing pond is so low, that desludging during the
      useful life span of the pond will most likely not be necessary. This leads to the
      important conclusion that excess sludge discharge from UASB reactors (a major
      factor in operational costs) may be omitted, if a polishing pond is used for post
      treatment. The bottom sludge had a high volatile solids concentration (58%) and
      the macronutrient fractions were also high (3.9% N and 1.1% P of the TSS mass).
      The bottom sludge was stable and could be dried directly without problems. The
      hygienic quality of the bottom sludge was very poor: about half the influent
      helminth eggs during one year of operation were found in the bottom sludge and
      the faecal coliform concentration was very high.

PMID- 11833735
TI  - Effect of anaerobic pretreatment on environmental and physicochemical
      characteristics of duckweed based stabilization ponds.
AB  - Duckweed based stabilization ponds, an alternative for wastewater treatment, are
      attracting a growing interest from researchers because they are basically a low
      cost technology, easy to built and operate, and produce tertiary quality
      effluents. Besides, this technology offers the possibility of resource recovery
      by producing high quality duckweed protein, which can be of further use. Since
      the technology is rather new, there are many aspects to be studied before its
      full-scale implementation. It is necessary to gain sound knowledge of the basic
      principles of the complex processes occurring in the system, as well as of the
      practical aspects of design and operation. The presence of a layer of duckweed on
      the surface is expected to produce different environmental and physicochemical
      conditions in the water from those found in conventional stabilization ponds.
      These environmental and physicochemical conditions affect both plant growth and
      biological treatment processes in the system, therefore it is important to
      determine their behavior in a duckweed system and how they can be affected by an
      anaerobic pretreatment. Continuous flow pilot plants composed of seven ponds in
      series were operated with artificial substrate under two different conditions:
      with anaerobic pretreatment and without anaerobic pretreatment. The flow was kept
      constant during the operation. Conditions such as pH, temperature, dissolved
      oxygen, alkalinity, conductivity, chemical oxygen demand, biochemical oxygen
      demand, total and ammonium nitrogen, nitrites and nitrates, and phosphorus were
      evaluated in the system under steady state conditions. The main conclusions from
      the study include the following: pH, temperature and oxygen profiles are more
      stable in duckweed ponds than in conventional stabilization ponds; anaerobic
      pretreatment has a significant effect on the oxygen concentration in the system
      and on the organic matter removal but not on the nutrient removal.

PMID- 11833736
TI  - Cotreatment of sewage and septage in waste stabilization ponds.
AB  - A one year study was carried out in a waste stabilization ponds system where
      septage and sewage are cotreated. The system consists of two septage ponds which
      operate alternately followed by two ponds in series which receive the combined
      effluent. The septage ponds also act as evaporation ponds for the accumulated
      sludge. The monitoring program was divided in two phases. The results of the
      first phase indicate that the effluent of septage ponds has an adequate quality
      to be discharged into the waste stabilization ponds designed to treat sewage and
      that is possible to use the septage ponds to dry the accumulated sludge. Further
      investigation is needed to find suitable post-treatment of the sludge in order to
      use it in agriculture.

PMID- 11833737
TI  - Role for brain-derived neurotrophic factor in learning and memory.
AB  - In addition to its actions on neuronal survival and differentiation, brain
      derived neurotrophic factor (BDNF) has a role in the regulation of synaptic
      strength. Long-term potentiation, a form of synaptic plasticity, is markedly
      impaired in BDNF mutant mice, but the changes were restored by the re-expression
      of BDNF. BDNF also influences the development of patterned connections and the
      growth and complexity of dendrites in the cerebral cortex. These results suggest
      a role for BDNF in learning and memory processes, since memory acquisition is
      considered to involve both short-term changes in electrical properties and long
      term structural alterations in synapses. Memory acquisition is associated with an
      increase in BDNF mRNA and TrkB receptor activation in specific brain areas.
      Moreover, the pharmacologic and genetic deprivation of BDNF or its receptor TrkB
      results in severe impairment of learning and memory in mice, rats and chicks. The
      effect of BDNF on learning and memory may be linked to the modulation of NMDA and
      non-NMDA receptor functions as well as the expression of synaptic proteins
      required for exocytosis. Activation of the mitogen-associated protein kinase
      and/or phosphatidylinositol 3-kinase signaling pathways may be involved in BDNF
      dependent learning and memory formation. It is concluded that BDNF/TrkB signaling
      plays an important role in learning and memory.

PMID- 11833738
TI  - Low frequency noise enhances cortisol among noise sensitive subjects during work
      performance.
AB  - Salivary free cortisol concentration, rated stress and annoyance were determined
      in 32 subjects before, during and after carrying out a battery of performance
      tasks for 2 hours during exposure to ventilation noise, with dominant low
      frequencies (low frequency noise) or a flat frequency spectrum (reference noise).
      Both noises had a level of 40 dBA. All subjects were studied on two occasions and
      were exposed to both noises in strict rotation. Subjects were categorised as high
      or low-sensitive to noise in general and low frequency noise in particular on
      the basis of questionnaires. Cortisol concentrations during the task were not
      significantly modulated by the noises or related to noise sensitivity alone. The
      normal circadian decline in cortisol concentration was however significantly
      attenuated in subjects high-sensitive to noise in general, when they were exposed
      to the low frequency noise. This noise was rated as more annoying and more
      disruptive to working capacity than the reference noise. The study showed
      physiological evidence of increased stress related to noise sensitivity and noise
      exposure during work. This is the first study to demonstrate an effect of
      moderate levels of noise on neuroendocrine activity. The impact of long-term
      exposure to moderate noise levels, and particularly low frequency noise, in the
      workplace deserves further investigation.

PMID- 11833739
TI  - Lysophosphatidic acid stimulates nuclear and cytoplasmic maturation of golden
      hamster immature oocytes in vitro via cumulus cells.
AB  - Lysophosphatidic acid (LPA), a member of the phospholipid autacoid family, is
      induced in incubated human follicular fluid by lysophospholipase D. It is well
      known that LPA functions as a growth factor and the hypothesis that LPA in human
      follicular fluid takes a part in meiosis of oocytes is quite plausible. We
      studied the effects of LPA on the maturation of golden hamster immature oocytes
      in vitro. Hamster oocytes with a germinal vesicle were cultured in Tyrode's
      albumin lactate pyruvate (TALP) medium with 10(-5) M LPA, 10 ng/ml epidermal
      growth factor (EGF), 30 ng/ml insulin-like growth factor-1, 1 ng/ml tumor growth
      factor-alpha or 1 ng/ml basic fibroblast growth factor. The nuclear maturation
      rates in the LPA and EGF groups were significantly higher than in the control
      group and the other growth factors did not show any stimulatory effect (LPA
      group; 74.3% [75/101], EGF group; 82.4% [89/108] vs. control group; 60.2%
      [59/98], p < 0.05, p < 0.01, respectively). When the cells of cumulus were
      removed, EGF and LPA did not increase the nuclear maturation rates. Cotreatment
      EGF and LPA did not significantly enhance the stimulatory effect observed with
      LPA alone on maturation in vitro. The penetration rate determined by the zona
      free hamster oocyte test was significantly higher in the LPA group than in the
      control group (26.7% vs. 13.2%, p < 0.05) and was comparable with that of oocytes
      matured in vivo. In conclusion, LPA stimulates the nuclear and cytoplasmic
      maturation of hamster immature oocytes via cumulus cells.

PMID- 11833740
TI  - Simple and rapid physico-chemical methods to examine action of antimalarial drugs
      with hemin: its application to Artemisia annua constituents.
AB  - Malaria is a major health problem in many countries and according to an estimate
      of the WHO, more than 500 million infections occur per year. Artemisinin, a
      sesquiterpene from Artemisia annua L., has received considerable attention as a
      promising and potent antimalarial drug for its stage speciticity, its rather low
      toxicity, effectiveness against drug-resistant Plasmodium species and activity
      against cerebral malaria. From recent studies it seems that hemin is primarily
      involved in the antimalarial activity of the constituents of Artemisia annua L.
      Thus, the interaction of a compound with hemin may represent a crucial screening
      test to define its efficacy. In this study the interaction between artemisinin
      and hemin was investigated by UltraViolet/Visible (UV/Vis) spectrophotometry and
      High Performance Liquid Chromatography/Diode Array Detector/Mass Spectrometry
      (HPLC/DAD/MS). In addition, some flavonols isolated from Artemisia annua L. were
      also tested to investigate their possible role in the interaction between
      artemisinin and hemin. These two simple physico-chemical methods can be useful as
      rapid and widespread screening methods for the search of other alkylating
      antimalarial constituents from natural sources or for the evaluation of the
      activity of semisynthetic analogues of artemisinin.

PMID- 11833741
TI  - Characterization of mouse melanoma cell lines by their mortal malignancy using an
      experimental metastatic model.
AB  - We characterized the metastatic ability and mortality of four different mouse
      melanoma cell lines, B16-F0, -F1, -F10 and -BL6. B16-F0 is the parent cell line.
      B16-F1 was obtained by a one-time selective procedure and B16-F10 by a ten-time
      selective procedure using Fidler's method. B16-BL6 derived from B16-F10 has much
      more invasive activity than B16-F10. To investigate the difference in mortal
      malignancy among B16-F0, -F1, -F10 and -BL6, we examined the survival time of
      syngeneic C57BL/6Cr mice intravenously inoculated with these cells. As a control,
      we used the C57BL/6J-embryo mouse fibroblast-like semi-normal cell line. The
      ability to form lung metastatic nodules in mice gradually increased in the order:
      B16-F0, -F1, and -F10 (=-BL6). C57BL/6J-embryo cell (1 x 10(5)/mouse)-inoculated
      mice survived for over 46 days. B16-F0, -F1, -F10 and -BL6 (1 x 10(5)/mouse)
      inoculated mice survived 31.4+/-4.4 (7), 25.7+/-2.8 (7), 23.6+/-1.5 (7) and
      25.3+/-2.3 (7) days [mean+/-S.D. (number of mice)], respectively. According to
      the Mann-Whitney test, the B16-F0 inoculated group versus -F1 inoculated group
      (P<0.05), -F0 inoculated group versus -BL6 inoculated group (P<0.05), and -F0
      inoculated group versus -F10 inoculated group (P<0.01) were significantly
      different, but the B16-F1 group versus -F10 group, -F1 group versus -BL6 group,
      and -F10 group versus -BL6 group were not. These results suggest that mortal
      malignancy is not necessarily correlated with lung-colonizing potential and even
      only one-time selected B16-F0 mouse melanoma cells are useful as an experimental
      metastatic model in vivo.

PMID- 11833742
TI  - Comparison of gene expression patterns and migration capability at quiescent and
      proliferating vascular smooth muscle cells stimulated by cytokines.
AB  - The changes of the gene expression patterns and the migration capability of
      vascular smooth muscle cells (VSMC) at the quiescent and proliferating states
      were investigated after VSMC was stimulated by cytokines. VSMC migration was
      measured using a model of wounding injury of confluent cultured cells and a
      Boyden chamber assay. The migration distance of the quiescent VSMC induced by
      cytokines bFGF, IL-1beta and TNF-alpha was 5.8, 4.7, and 4.2 times as long as
      that of the control group, respectively. However, the migration distance of the
      proliferating VSMC was only one-fourth of the quiescent cells under the same
      effects. The results of Boyden chamber assay indicated that VSMC was capable of
      degrading collagen and traversed the pores of membrane barriers in response to
      bFGF as a chemoattractant, and VSMC number across the membrane was markedly
      increased as concentration gradient of bFGF ascended. Northern blot and nuclear
      run-off assay showed that bFGF not only stimulated the expression of migration
      related matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of
      metalloproteinase-2 (TIMP-2) but also enhanced the transcription of proliferation
      related osteopontin (OPN) and c-jun genes in the quiescent VSMC. bFGF could
      moderately increase the expression of OPN and c-jun, but had no significant
      effect on the expression of MMP-2 and TIMP-2 in the proliferating cells under the
      same conditions. These findings suggest that VSMC migration capability and the
      expression activity of migration- and proliferation-related genes were
      significantly distinct for the quiescent and proliferating VSMC. The cellular
      migration capability and the expression activity of migration-related genes in
      the quiescent VSMC were much higher than those in the proliferating cells in
      response to cytokines.

PMID- 11833743
TI  - Effect of epidermal growth factor on intestinal adaptation after allogeneic small
      bowel transplantation in rats.
AB  - We reported that epidermal growth factor (EGF) stimulated graft adaptation in a
      rat model of syngeneic small bowel transplantation. However, graft rejection is a
      severe problem with clinical small bowel transplantation, because small
      intestinal wall contains large amounts of lymphoid tissue. Studies were performed
      to investigate the effect of EGF on allogeneic graft adaptation after small bowel
      transplantation in rats treated with an immunosuppressant FK506. The transplanted
      animals received intraperitoneally EGF or saline (untreated) after surgery and
      were examined for analysis one week later. EGF-treated group markedly enhanced
      the water absorption and induction of sodium glucose cotransporter (SGLTI) as
      compared with EGF-untreated group. EGF-treated group also increased the mucosal
      crypt depth and its cell proliferating rate, although there was no significant
      difference in the mucosal villus height between the two groups. These results
      indicate that EGF accelerates intestinal allograft adaptation in part by the
      recovery of mucosal structure and function after small bowel transplantation in
      rats. EGF may have relevance to promote graft function in clinical small
      intestinal transplantation.

PMID- 11833744
TI  - Hydrogen peroxide induced chemokine production in the glia-rich cultured
      cerebellar granule cells under acidosis.
AB  - We have documented the time-dependent production of chemotactic cytokine, i.e.,
      IL-8, in the extracellular fluid of astrocyte-rich cultured rat cerebellar
      granule cells under acidified conditions. In this paper, the mechanism of this
      production was evaluated based on the production of hydrogen peroxide (H2O2).
      Significant and time-dependent increases of cytosolic H2O2 were detected under
      acidosis in astrocyte-rich cultured cell. Upon exposure to 10 microM H2O2,
      significant levels of IL-8 appeared in the extracellular fluid of astrocyte-rich
      cells, although an initial transient increase of IL-8 was also seen in the
      intracellular space. Concurrently, after H2O2 exposure cell injury and a delayed
      increase of cytosolic Ca2+ levels were detected in astrocyte-rich cells. However,
      in the absence of extracellular Ca2+, the cell injury and the increase of IL-8
      production were significantly attenuated. A synergistic effect of cyclosporine A
      (an inhibitor of the Ca2+/calmodulin-regulated protein phosphatase) and
      trifluoperazine (an inhibitor of phospholipase A2) on the suppression of H2O2
      induced IL-8 production was clearly evident. These results suggest that
      extracellular acidosis induced Ca2+-dependent H2O2 production, which in turn
      stimulated IL-8 expression. which is regulated by the cytosolic Ca2+ cascade.
      Thus, the production of IL-8 from glia cells may have a role in regulating in the
      process of cell injury.

PMID- 11833745
TI  - Amyloid-beta-protein (A beta) (25-35)-associated free radical generation is
      strongly influenced by the aggregational state of the peptides.
AB  - We investigated whether or not the Amyloid-beta-protein (A beta) itself
      spontaneously generates free radicals using electron spin resonance (ESR)
      spectroscopy while also monitoring the aggregational state of A beta and A beta
      induced cytotoxicity. The present results demonstrated a four-line spectrum in
      the presence of A beta25-35 with N-tert-butyl-alpha-phenylnitrone (PBN) but not
      in the presence of PBN alone in phosphate-buffered saline (PBS). The fact that
      the four-line spectrum obtained for the A beta25-35/PBN in PBS was completely
      abolished in the presence of the iron-chelating agent Desferal demonstrated the
      observed four-line spectrum to be iron-dependent. On the other hand, A beta25-35
      with PBN in phosphate buffer (PB) did not produce any definite four-line
      spectrum. the present results showed the amyloid fibril formation of A beta25-35
      in PBS to be much higher than that of A beta25-35 in PB. Moreover, A beta-induced
      cytotoxicity assays showed A beta incubated in PBS to be more cytotoxic than that
      incubated in PB. These results thus demonstrate that A beta(25-35)-associated
      free radical generation is strongly influenced by the aggregational state of the
      peptides.

PMID- 11833746
TI  - Requirements for providing optimal nutrition care: passion, evidence, and
      compassion--presidential address to the 24th Clinical Congress, January 24, 2000.

PMID- 11833747
TI  - Is gold always present in a "gold standard"?

PMID- 11833748
TI  - Accuracy of predictive methods to estimate resting energy expenditure of
      thermally-injured patients.
AB  - BACKGROUND: The purpose of this study was to evaluate the bias and precision of
      46 methods published from 1953 to 2000 for estimating resting energy expenditure
      (REE) of thermally injured patients. METHODS: Twenty-four adult patients with >
      or =20% body surface area burn admitted to a burn center who required specialized
      nutrition support and who had their REE measured via indirect calorimetry (IC)
      were evaluated. Patients with morbid obesity, human immunovirus, malignancy,
      pregnancy, hepatic or renal failure, neuromuscular paralysis, or those requiring
      a FiO2 >50% or positive end expiratory pressure (PEEP) > or =10 cm H2O were
      excluded. One steady-state measured REE measurement (MEE) was obtained per
      patient. The methods of Sheiner and Beal were used to assess bias and precision
      of these methods. The formulas were considered unbiased if the 95% confidence
      interval (CI) for the error (kilocalories per day) intersected 0 and were
      considered precise if the 95% CI for the absolute error (%) was within 15% of
      MEE. RESULTS: MEE was 2780+/-567 kcal/d or 158%+/-34% of the Harris Benedict
      equations. None of the methods was precise (< or =15% CI error). Over one-half
      (57%) of the 46 methods had a 95% confidence interval error >30% of the MEE.
      Forty-eight percent of the methods were unbiased, 33% were biased toward
      overpredicting MEE, and 19% consistently underpredicted MEE. The pre-1980s
      methods more frequently overpredicted MEE compared with the 1990 to 2000 (p <
      .01) and 1980 to 1989 (p < .05) published methods, respectively. The most precise
      unbiased methods for estimating MEE were those of Milner (1994) at a mean error
      of 16% (CI of 10% to 22%), Zawacki (1970) with a mean error of 16% (CI of 9% to
      23%), and Xie (1993) at a mean error of 18% (CI of 12% to 24%). The "conventional
      1.5 times the Harris Benedict equations" was also unbiased and had a mean error
      of 19% (CI of 9% to 29%). CONCLUSIONS: Thermally injured patients are variably
      hypermetabolic and energy expenditure cannot be precisely predicted. If IC is not
      available, the most precise, unbiased methods were those of Milner (1994),
      Zawacki (1970), and Xie (1993).

PMID- 11833749
TI  - Effects of 2 lipid emulsions (LCT versus MCT/LCT) on the fatty acid composition
      of plasma phospholipid: a double-blind randomized trial.
AB  - BACKGROUND: Fatty acids from the diet or from IV fat emulsions are incorporated
      into the plasma and cell membrane phospholipids and act as substrates in the
      synthesis of eicosanoids. This study reports the effect of 2 parenteral lipid
      emulsions in plasma phospholipids fatty acids. METHODS: A total of 83 patients
      aged 18 to 75 years were randomized to receive long-chain triglycerides (LCT) or
      50/50 mix of long- and medium-chain triglyceride emulsion (LCT/MCT). Blood
      samples were collected at baseline and at weekly intervals for 28 days. Plasma
      phospholipid fatty acids were measured by gas chromatography. RESULTS: Patients
      receiving LCT versus MCT/LCT emulsion have an increase in 18:2n6 and a decrease
      in 20:4n6 and 22:4n6 after 7, 14, and 21 days of treatment with parenteral
      nutrition. Phospholipid fatty acids at 15 days of treatment with parenteral
      nutrition with LCT versus MCT/LCT for 18:2n6 were 17.30% versus 22,90% (p < .05),
      for 20:4n6 10.44% versus 8.38% (p < .05), and for 22:4n6 0.51% versus 0.40% (p <
      .05). The 20:4n6 percentage inversely correlated with the percentage of 18:2n6 on
      days 7, 14, and 21: regression coefficients: -7.40 (p < .001), -7.39 (p < .001),
      and 5.70 (p < .001), respectively. CONCLUSIONS: Parenteral lipid emulsions modify
      fatty acid profiles in plasma phospholipids. MCT/LCT emulsions produce in
      phospholipids a fatty-acid profile that is closer to normality than that achieved
      with LCT emulsions. These changes in phospholipid fatty acids are suggestive of
      an inhibition of A-5-desaturase in patients who received LCT emulsions.

PMID- 11833750
TI  - Effects of cyclosporine A and prednisone treatment on mixed meal disposition in
      dogs with hepatic denervation.
AB  - BACKGROUND: Compared with untreated dogs, normal dogs treated for 7 days with
      cyclosporine A and prednisone exhibited a 25% reduction in the absorption of
      glucose from a mixed meal and a 4- to 5-fold increase in net hepatic glucose
      uptake, without reduction of postprandial glycemia. The hepatic nerves are also
      involved in directing postprandial glucose disposition. Therefore, we
      hypothesized that the combination of immunosuppressive therapy and hepatic
      denervation would create additional alterations in the disposition of glucose
      from a mixed meal. METHODS: Six 24-hour-fasted conscious dogs that had undergone
      surgical hepatic denervation (DN) and received cyclosporine A 15 mg/kg daily and
      prednisone 5 mg twice daily for 7 consecutive days before study (DN + CyP group)
      received an intragastric mixed-meal feeding over 30 minutes. The results were
      compared with those from a group of 8 normally innervated dogs receiving the same
      immunosuppressives (CyP group). RESULTS: Arterial blood glucose concentrations
      remained elevated over basal in both groups at the end of the 480 minutes
      postprandial period. The arterial plasma insulin response was no different in the
      2 groups (area under the curve 119+/-25 and 100+/-40 nmol/L in DN + CyP and CyP,
      respectively). In both groups, net gut glucose output was equivalent to
      approximately 45% of the glucose in the meal, and net hepatic glucose uptake
      accounted for approximately 54% to 66% of the absorbed glucose. Arterial blood
      lactate concentrations and net hepatic lactate output were not different between
      groups at any time. CONCLUSIONS: Immunosuppressive therapy is responsible for
      most of the alterations in postprandial carbohydrate metabolism observed in this
      model; the lack of hepatic nerves has little additional impact.

PMID- 11833751
TI  - Diet, length of gestation, and fecal short chain fatty acids in healthy premature
      neonates.
AB  - BACKGROUND: Excretion of fecal short-chain fatty acids (SCFAs) may indicate
      changes in colonic or colonocyte metabolism. The aim of this study was to detect
      the influence of gestational age and feeding practices on SCFA concentrations and
      profiles in healthy preterm infants. METHODS: A total of 198 fecal samples (28
      infants) were collected from 8 to 21 days of age from 3 groups of preterm infants
      born at 33 to 37 weeks of gestation and fed either breast milk (group I) or
      Nutramigen, a lactose-free formula (group II), and extremely preterm infants born
      before 33 weeks of gestation and fed breast milk (group III). Total SCFA
      concentrations and SCFA profiles were analyzed using a gas chromographic (GC)
      procedure. RESULTS: Total fecal SCFA excretion did not differ significantly
      between group I (mean, 24.0 micromol/g; range, 1.3 to 118.8 micromol/g) and group
      II (mean, 23.0 micromol/g; range, 3.0 to 73.3 micromol/g). Conversely,
      differences occurred between SCFA profiles and became significant after day 17.
      The main differences were a significant increase in the butyric acid
      concentration (12% versus 30%) with group II. Compared with group I, fecal SCFA
      concentrations were 3.2-fold lower (7.4 micromol/g; range, 0.3 to 37.4
      micromol/g) in group III with no significant changes in the profiles.
      CONCLUSIONS: Fecal SCFA excretion may vary in absence of any digestive disease.
      During this study, in terms of gestational age, total SCFA concentrations were
      significantly lower in extremely premature infants compared with infants born
      less premature, despite their known higher deficiency in intestinal lactase
      activity. In terms of diet, the absence of lactose did not lead to a decrease in
      colonic fermentation and induced changes in SCFA patterns. These new baseline
      data may offer clues to further development of milk formulas.

PMID- 11833752
TI  - Choline and vitamin B12 deficiencies are interrelated in folate-replete long-term
      total parenteral nutrition patients.
AB  - BACKGROUND: Choline has recently been recognized as an essential nutrient, in
      part based on deficiency data in long-term home total parenteral nutrition (TPN)
      patients. Choline, a methyl donor in the metabolism of homocysteine, is
      intricately related to folate status, but little is known about choline and
      vitamin B12 status. Long-term TPN patients are also subject to vitamin B12
      deficiency. OBJECTIVE: The objective of the study was to evaluate any interaction
      between choline, vitamin B12, and folate in patients with severe malabsorption
      syndromes, requiring long-term TPN. DESIGN: Plasma free choline, serum and red
      blood cell (RBC) folate, serum vitamin B12 methylmalonic acid, B6, and plasma
      total homocysteine concentrations were assayed by standard methods. Low choline
      was defined as values that fall 1 to < or =3 and marked low choline concentration
      as >3 SD below the control mean. RESULTS: Both low choline concentrations (52%
      were marked low, 33% low, 14% normal) and elevated methylmalonic acid
      concentrations (47%) were prevalent. Choline concentration was significantly
      lower and RBC folate higher in patients with elevated methylmalonic acid. Total
      homocysteine elevations were rare (3 of 21) and mild. CONCLUSIONS: These data
      suggest a strong interaction between vitamin B12 and choline deficiencies and
      folate status in this population, which may be due in part to variations in
      vitamin and choline delivery by TPN. Folate adequacy may increase B12 use for
      homocysteine metabolism, thus limiting B12 availability for methylmaIonic acid
      metabolism. Choline use may also increase, and choline deficiency may worsen if
      choline substitutes when the vitamin B12 side of the homocysteine metabolic
      pathway cannot be used.

PMID- 11833754
TI  - Cardiomyopathy in association with selenium deficiency: a case report.
AB  - A 46-year-old man developed "dilated cardiomyopathy" probably caused by selenium
      deficiency while on total parenteral nutrition (TPN). This development emphasizes
      the role of considering selenium deficiency as a reversible cause of unexplained
      cardiomyopathy in impaired nutritional state.

PMID- 11833753
TI  - Comparison of standard and immune-enhancing oral formulas in asymptomatic HIV
      infected persons: a multicenter randomized controlled clinical trial.
AB  - BACKGROUND: Both standard and immune-enhancing oral formulas are widely used to
      forestall HIV wasting and to promote immune function. However, there is little
      scientific evidence to support the differential effects of these formulas in
      asymptomatic HIV disease. The aim of this study was to compare the effects of an
      immune-enhancing oral formula and a standard oral formula on nutrition and immune
      measures in asymptomatic HIV-infected persons. A secondary aim was to evaluate
      the feasibility of maintaining a diverse sample of outpatients on a long-term
      oral formula protocol. METHODS: In this multicenter controlled nonblinded study,
      90 asymptomatic HIV-infected persons with CD4 cell counts between 275 and 550
      cells/mm3 were randomized to a control group; a standard oral formula group
      (Ensure Plus); or an immune-enhancing oral formula group (Advera). All groups
      received basic nutrition counseling. Participants were evaluated on nutrition,
      immune, and feasibility measures at 3-month intervals during the 12-month study
      period. Differences in nutrition and immune measures among the 3 groups were
      analyzed using the Kruskal-Wallis and Wilcoxon tests. Wilcoxon tests and
      correlation coefficients were used to analyze feasibility data. RESULTS: Sixty
      six outpatients completed the 12-month study protocol. Among the 3 groups, there
      were no significant differences with respect to body weight, bioelectrical
      impedance analysis (BIA)-derived body cell and fat mass, daily caloric intake,
      and serum albumin at any of the study visits. Moreover, absolute CD4+ T
      lymphocytes and percentages did not significantly differ at any time point among
      the 3 groups. Acceptability and tolerance of the formulas were high for both the
      standard and immune-enhancing oral formula groups. CONCLUSIONS: Within the
      context and limitations of this study, standard and immune-enhancing oral
      formulas consumed daily for 1 year had no differential effects on nutrition or
      immune parameters in asymptomatic HIV-infected persons.

PMID- 11833755
TI  - Immunonutrition in the critically ill.

PMID- 11833756
TI  - Be a good neighbor.

PMID- 11833757
TI  - Anaerobic co-digestion of aircraft deicing fluid and municipal wastewater sludge.
AB  - At many airports, aircraft deicing fluid and precipitation mix, becoming aircraft
      deicing runoff having a 5-day biochemical oxygen demand (BOD5) of 10(2) to 10(6)
      mg/L. Publicly owned treatment works can be used for aerobic biological
      treatment; however, it may be more economical to use anaerobic digesters to
      codigest a mixture of aircraft deicing fluid and sludge. The objectives of this
      investigation were to determine benefits and appropriate propylene glycol
      aircraft deicing fluid loadings to anaerobic codigesters. Results demonstrate
      aircraft deicing fluid can be successfully codigested to produce methane;
      supernatant BOD5 and Kjeldahl nitrogen concentration were not higher in
      codigesters compared to a conventional digester. Aircraft deicing fluid loadings
      as high as 1.6 g chemical oxygen demand (COD)/L x d were sustainable in
      codigesters, whereas system fed only aircraft deicing fluid with nutrients and
      alkalinity achieved a loading of 0.65 g COD/L x d. The sludge used increased
      digester alkalinity and provided nitrogen, iron, nickel, cobalt, and biomass
      required for methanogenesis. The deicer provides organics for increased methane
      production.

PMID- 11833758
TI  - Characterization and evaluation of a novel exalting round-plate photocatalytic
      reactor.
AB  - A novel reactor, the exalting round-plate photocatalytic reactor (ERPPR), was
      designed and evaluated. Residence time and light intensity distributions were
      determined by stimulus-response experimentation and an irradiation meter,
      respectively. The effects of hydraulic loading of the round plate and aeration on
      the photocatalytic degradation of azo dye were investigated during different
      conditions. Experimental results show that the ERPPR is intermediate between a
      completely stirred tank reactor and a plug-flow reactor. Mean hydraulic loadings
      at different rotational speeds were significantly influenced by the reaction rate
      for dye decolorization. Photodegradation of the dye, however, was not
      significantly influenced by the amount of oxygen gas aerated, except when
      aerating with pure oxygen. Results further indicate that the photoreaction
      atmosphere of the ERPPR depends on mass transfer between gas and liquid on the
      round plate. The primary role of aeration is to mix catalyst and solution.

PMID- 11833759
TI  - Oxygen fluxes and ammonia removal efficiencies in constructed treatment wetlands.
AB  - Ammonia-removal efficiency in constructed wetlands is often limited by the amount
      of oxygen available in the system. In this study, the oxygen-transfer rates to
      laboratory-scale, subsurface-flow and free-water-surface constructed wetlands
      were quantified for two input concentrations of ammonia, 10 and 50 mg nitrogen/L,
      both with and without Typha latifolia. Rates of oxygen diffusion into the
      subsurface-flow constructed wetlands were 6.01 to 7.92 g/m2 x d and were strongly
      correlated with ammonia concentration in the water. In contrast, low oxygen
      diffusion rates of 1.36 to 1.76 g/m2 x d were observed for the free-water-surface
      system. The presence of Typha latifolia had small but consistent effects on
      atmospheric oxygen-diffusion rates and ammonia-removal efficiencies in both the
      subsurface-flow and free-water-surface systems. The observed small effects were
      consistent with measurements of oxygen inputs from T. latifolia roots. Only
      approximately 0.023 g/m2 x d of oxygen was released from roots of T. latifolia,
      as measured using the titanium (III) citrate buffer method. The results for the
      ammonia-removal rates of the laboratory-scale constructed wetlands were further
      verified using pilot-scale constructed wetlands under greenhouse conditions.

PMID- 11833760
TI  - Microbial risks from wastewater irrigation of salad crops: a screening-level risk
      assessment.
AB  - The potential health risk from viruses, associated with the consumption of
      lettuce crops spray irrigated with secondary-treated municipal effluent, has been
      evaluated in the first level investigation of a tiered microbial risk assessment.
      The study assessed the impact of two factors on the estimated risk of infection:
      a suitable probability density function for the occurrence of human enteroviruses
      in irrigation water and appropriate die-off rates for viruses on lettuce crops. A
      Monte Carlo simulation using a log-normal and a nonparametric, kernel estimated
      probability density function indicated that slight changes in the upper tail of
      the probability density function had a relatively low effect on the estimated
      infection rates. Predicted infection rates were much more sensitive to the decay
      rate of viruses than occasional high virus numbers. The median and 99th
      percentile risks of infection from the overall model were 0.10 and 0.51/10000
      lettuce consumers, respectively, indicating possible human health concern, and
      the justification of a more detailed microbial risk assessment.

PMID- 11833761
TI  - Aerated biofiltration for simultaneous removal of iron and polycyclic aromatic
      hydrocarbons from groundwater.
AB  - Filters incorporating the principles of biological accumulation have been used in
      Europe to remove iron from drinking water for many years. The authors of this
      study hypothesized that a modified biological iron-removing filter could
      simultaneously degrade polycyclic aromatic hydrocarbons (PAHs) in groundwater
      impacted by former manufactured gas plant (MGP) operations. The MGP-impacted
      groundwater obtained for this study had an average total iron concentration of
      3.8 mg/L and an average total dissolved PAH concentration of 3.0 mg/L.
      Naphthalene was the primary PAH, with an average concentration of 2.8 mg/L. The
      groundwater was passed intermittently through duplicate gravel-media columns at
      15 to 30 cm/d for 2 months while filtered air was delivered countercurrently at 4
      mL/min. The columns remained partially saturated throughout the study. Flooding,
      which would have indicated plugging of the columns, was not observed, and the
      pressure needed to aerate the columns remained constant. Total iron in the
      effluent was below the detection limit of 0.1 mg/L (97% removal) for 40 days of
      operation. Removal of total PAHs, primarily two- and three-ring compounds,
      averaged 99%. This single-stage treatment process represents an economical
      alternative to biological treatment systems currently available for MGP-impacted
      groundwater that require pretreatment to remove iron.

PMID- 11833762
TI  - Measurement of microbial numbers and biomass contained in thermophilic anaerobic
      reactors.
AB  - This paper describes the determination of the microbial population in terms of
      the number, biomass, and composition of single- and two-phase, laboratory-scale
      thermophilic (55 degrees C) anaerobic reactors under steady-state conditions.
      Epifluorescence microscopy with 4',6-diamidine-2-phenylindole (DAPI) as
      fluorochrome was used to determine the total number of microorganisms in the
      reactors, and autofluorescence microscopy was used to determine the total
      methanogenic bacteria populations. The results obtained by the direct count
      methods were compared to the quantity of biomass contained in the system, which
      was determined by volatile suspended solids. The concentration of acidogenic
      bacteria was estimated by subtraction of the autofluorescence results from those
      of the DAPI epifluorescence microscopy. The viable bacterial population was
      determined by plating techniques using an anaerobic chamber. The total bacterial
      and methanogenic populations of single-stage digesters increase when the
      hydraulic retention time decreases; nevertheless, the percentages of the
      principal bacterial groups (acidogenic and methanogenic) remain constant at 87%
      and 13%, respectively. In the two-stage reactors, the percentages of the
      acidogenic and methanogenic groups are 99% and 26% of the total population in the
      acidogenic and methanogenic reactors, respectively. In the single-stage reactors,
      biomass determinations can be used to estimate microbial concentrations, and vice
      versa, as there is a high positive correlation between microorganism
      concentration and biomass. The syntrophic relationship between the bacteria
      involved in the anaerobic process is a possible explanation for the low values of
      viable population obtained in the reactors studied. Nevertheless, there is a high
      correlation between direct counts by epifluorescence microscopy and viable plate
      counts for the combined system studied.

PMID- 11833763
TI  - Responses of Onondaga Lake, New York, to early stages of rehabilitation:
      unanticipated ecosystem feedbacks.
AB  - Responses of polluted Onondaga Lake, New York, to early stages of a phased
      program to rehabilitate the lake from the effects of domestic waste inputs are
      documented. The analysis is based on more than 10 years of paired monitoring of
      the effluent (total ammonia and total phosphorus) of a wastewater treatment plant
      (WWTP) that discharges to the lake as well as the lake itself (including total
      ammonia, nitrite, total and dissolved forms of phosphorus, plankton biomass and
      composition, Secchi disc transparency, and zebra mussel density). Major
      reductions in total ammonia and total phosphorus loading relative to the
      preceding decade are reported for the WWTP for the November 1998 through October
      1999 interval. Dramatic and, in some cases, unanticipated changes in the lake's
      water quality and biota in response to the reductions in loading are documented
      for the April to October interval of 1999 including: (1) major decreases in total
      ammonia concentrations and improved status with respect to ammonia toxicity
      standards, (2) development of dense populations of zebra mussels, (3) decreases
      in fall concentrations of nitrite and improved status with respect to the related
      toxicity standard, (4) decreases in total phosphorus and total dissolved
      phosphorus concentrations, and (5) a severe Microcystis (phytoplankton) bloom
      that caused nuisance conditions and poor clarity. The zebra mussel invasion is
      attributed to the reductions in total ammonia concentrations to below toxic
      levels. The Microcystis bloom was probably related to the abrupt increase in the
      zebra mussel population. Additional reductions in phosphorus loading from the
      WWTP will be required to limit phytoplankton production and avoid the potential
      for continued nuisance conditions. Potential complications in resolving lake
      responses to future reductions in loading associated with the zebra mussel
      invasion are considered.

PMID- 11833764
TI  - Comparison of fatty acid composition and kinetics of phosphorus-accumulating
      organisms and glycogen-accumulating organisms.
AB  - It was demonstrated that glycogen-accumulating organisms (GAOs) were able to
      compete with phosphorus-accumulating organisms (PAOs) for acetate in a biological
      phosphorus removal (BPR) process, leading to a loss of BPR capability. Cellular
      fatty acid composition, which serves as a fingerprint for microbial
      identification, was used to determine microbial population change and to
      investigate the competition mechanisms of PAOs and GAOs. Analysis of cellular
      fatty acid composition indicated that PAOs grown with acetate and glucose were
      different species and that GAOs and PAOs grown with the same substrate were also
      different species. Glycogen-accumulating organisms seemed to coexist with PAOs
      even in a well-developed BPR process. The GAOs were able to accumulate more poly
      beta-hydroxybutyrate (PHB) and glycogen than PAOs during the anaerobic stage of
      the BPR process. The GAOs synthesized more in-cell glycogen than PAOs. The growth
      rate for PAOs was always greater than that for GAOs at various acetate or glucose
      concentrations, while GAOs had higher acetate uptake and PHB synthesis rates than
      PAOs. Therefore, GAOs are thought to compete with PAOs only at long solids
      retention times (> or = 20 days).

PMID- 11833765
TI  - Reduction of enteric microorganisms at the Upper Occoquan Sewage Authority Water
      Reclamation Plant.
AB  - The Upper Occoquan Sewage Authority (UOSA) Water Reclamation Plant, Centreville,
      Virginia, is a state-of-the-art wastewater treatment plant that was created to
      treat area wastewater and provide protection for the Occoquan Reservoir. This
      study investigated UOSA's unit processes as barriers to pathogenic as well as
      altemative and traditional-indicator microorganisms. Samples were collected once
      a month for 1 year from eight sites within UOSA's advanced wastewater reclamation
      plant. The eight sites were monitored for indicator bacteria total and fecal
      coliforms, enterococci, Clostridium, coliphage (the virus that infects
      Escherichia coli), human enteroviruses, and enteric protozoa. Overall, the plant
      was able to achieve a 5- to 7-log10 reduction of bacteria, 5-log10 reduction of
      enteroviruses, 4-log10 reduction for Clostridium, and 4.6-log10 reduction of
      protozoa. Total coliforms, enterococci, Clostridium, coliphage, Cryptosporidium,
      and Giardia were all detected in four or fewer samples of the final effluent. No
      enteroviruses or fecal coliforms were detected in the final effluent. The
      microbiological quality of reclaimed water and the reservoir water were compared.
      In every case, the treated wastewater was of a better quality than the ambient
      water in the reservoir, thus indicating that the reclaimed water will not
      adversely affect the water quality for downstream users.

PMID- 11833766
TI  - Effect of chlorine demand on the ammonia breakpoint curve: model development,
      validation with nitrite, and application to municipal wastewater.
AB  - Chlorine added during wastewater disinfection may be consumed through reactions
      with chlorine-demanding chemical species. In this study, a mechanistically based
      kinetic model for chlorine demand in the presence of ammonia was developed and
      validated with laboratory studies on ammonia-nitrite systems, and then applied to
      breakpoint curves obtained with wastewater samples. The model is a modification
      of kinetic models for chlorine-ammonia systems to include hypochlorous acid
      demand and monochloramine-demand reactions. The model accurately describes both
      laboratory-generated breakpoint curves with added nitrite and literature data. In
      a plant thought to be undergoing partial nitrification, breakpoint curves were
      consistent with high chlorine demand (i.e., small initial slopes and large doses
      to achieve the total chlorine maximum and breakpoint). A simplified kinetic model
      was also developed. Chlorine demand calculated from the simplified model was
      similar to chlorine demand from plant data. The simplified model was used to
      generate operating guidelines to calculate chlorine doses needed to overcome
      demand from nitrite or other sources.

PMID- 11833767
TI  - The human genome structure and organization.
AB  - Genetic information of human is encoded in two genomes: nuclear and
      mitochondrial. Both of them reflect molecular evolution of human starting from
      the beginning of life (about 4.5 billion years ago) until the origin of Homo
      sapiens species about 100,000 years ago. From this reason human genome contains
      some features that are common for different groups of organisms and some features
      that are unique for Homo sapiens. 3.2 x 10(9) base pairs of human nuclear genome
      are packed into 23 chromosomes of different size. The smallest chromosome - 21st
      contains 5 x 10(7) base pairs while the biggest one -1st contains 2.63 x 10(8)
      base pairs. Despite the fact that the nucleotide sequence of all chromosomes is
      established, the organisation of nuclear genome put still questions: for example:
      the exact number of genes encoded by the human genome is still unknown giving
      estimations from 30 to 150 thousand genes. Coding sequences represent a few
      percent of human nuclear genome. The majority of the genome is represented by
      repetitiVe sequences (about 50%) and noncoding unique sequences. This part of the
      genome is frequently wrongly called "junk DNA". The distribution of genes on
      chromosomes is irregular, DNA fragments containing low percentage of GC pairs
      code lower number of genes than the fragments of high percentage of GC pairs.

PMID- 11833768
TI  - Some aspects of the SOS response system--a critical survey.
AB  - The SOS system and SOS mutagenesis are frequently studied, or exploited to obtain
      an increase in mutagenicity of bacteria. Here a short survey is made of the
      phenomenon of SOS response with special attention to latest and less discussed
      data, especially the induction of the SOS system in response to cell starvation
      or mutation of certain genes and the role of inducible DNA polymerases.

PMID- 11833769
TI  - Detection of alkylation damage in human lymphocyte DNA with the comet assay.
AB  - The enzyme 3-methyladenine DNA glycosylase II (AlkA) is a bacterial repair enzyme
      that acts preferentially at 3-methyladenine residues in DNA, releasing the
      damaged base. The resulting baseless sugars are alkali-labile, and under the
      conditions of the alkaline comet assay (single cell gel electrophoresis) they
      appear as DNA strand breaks. AlkA is no t lesion-specific, but has a low activity
      even w ith undamagedbases. We have tested the enzyme at different concentrations
      to find conditions that maximise detection of alkylated bases with minimal attack
      on normal, undamaged DNA. AlkA detects damage in the DNA of cells treated with
      low concentrations of methyl methanesulphonate. We also find low background
      levels of alkylated bases in normal human lymphocytes.

PMID- 11833770
TI  - An introduction to DNA chips: principles, technology, applications and analysis.
AB  - This review describes the recently developed GeneChip technology that provides
      efficient access to genetic information using miniaturised, high-density arrays
      of DNA or oligonucleotide probes. Such microarrays are powerful tools to study
      the molecular basis of interactions on a scale that would be impossible using
      conventional analysis. The recent development of the microarray technology has
      greatly accelerated the investigation of gene regulation. Arrays are mostly used
      to identify which genes are turned on or off in a cell or tissue, and also to
      evaluate the extent of a gene's expression under various conditions. Indeed, this
      technology has been successfully applied to investigate simultaneous expression
      of many thousands of genes and to the detection of mutations or polymorphisms, as
      well as for their mapping and sequencing.

PMID- 11833771
TI  - Odyssey of agrobacterium T-DNA.
AB  - Agrobacterium tumefaciens, a plant pathogen, is characterized by the unique
      feature of interkingdom DNA transfer. This soil bacterium is able to transfer a
      fragment of its DNA, called T-DNA (transferred DNA), to the plant cell where T
      DNA is integrated into the plant genome leading to "genetic colonization" of the
      host. The fate of T-DNA, its processing, transfer and integration, resembles the
      journey of Odysseus, although our hero returns from its long trip in a slightly
      modified form.

PMID- 11833772
TI  - Effect of nuclear matrix attachment regions on transgene expression in tobacco
      plants.
AB  - Matrix attachment regions (MARs) are thought to participate in the organization
      and segregation of independent chromosomal loop domains. Although there are
      several reports on the action of natural MARs in the context of heterologous
      genes in transgenic plants, in our study we tested a synthetic MAR (sMAR) with
      the special property of unpairing when under superhelical strain, for its effect
      on reporter gene expression in tobacco plants. The synthetic MAR was a multimer
      of a short sequence from the MAR 3' end of the immunoglobulin heavy chain (IgH)
      enhancer. This sMAR sequence was used to flank the beta-glucuronidase (GUS)
      reporter gene within the T-DNA of the binary vector pBI121. Vectors with or
      without the sMARs were then used to transform tobacco plants by Agrobacterium
      tumefaciens. Transgenic plants containing the sMAR sequences flanking the GUS
      gene exhibited higher levels of transgene expression compared with transgenic
      plants which lacked the sMARs. This effect was observed independently of the
      position of the sMAR at the 5' side of the reporter gene. However, variation of
      the detected transgene expression was significant in all transformed plant
      populations, irrespective of the construct used.

PMID- 11833773
TI  - Modification of non-protein thiols contents in transgenic tobacco plants
      producing bacterial enzymes of cysteine biosynthesis pathway.
AB  - Conditions of achieving the maximal accumulation of sulfhydryl metabolites in the
      leaves of tobacco were explored. Simultaneous production of bacterial O
      acetylserine (thiol)-lyase and serine acetyltransferase resulted in the increased
      thiols contents as compared to single transformants and controls. However, leaf
      discs feeding experiments differently affected thiols concentration in different
      plant groups and suggested that the most promising strategy to obtain plants with
      a high level of non-protein thiol-containing compounds might be sulfate feeding
      to plants overproducing serine acetyltransferase.

PMID- 11833774
TI  - Electroporated intact BY-2 tobacco culture cells as a model of transient
      expression study.
AB  - Transfer of foreign genes into plant cells can be accomplished by several
      methods: agrobacterium-mediated, microinjection, biolistic particle bombardment
      and electroporation. The last one is frequently used for transfection of plant
      protoplasts for transient gene expression. Electroporation is a simple procedure
      and allows transfecting a large number of cells at one time. Square wave
      modulated porators are the most efficient for introducing expression cassettes
      into plant protoplasts. Based on a protocol developed by Wu & Feng (Plant Cell
      Reports, 1999, 18, 381-386), we optimized conditions for transfection of intact
      Nicotiana tabacum BY-2 cells using square wave-modulated electroporator. To
      simplify screening for transfected gene expression we used constructs with a GFP
      marker gene.

PMID- 11833775
TI  - Isoprenoid biosynthesis via 1-deoxy-D-xylulose 5-phosphate/2-C-methyl-D
      erythritol 4-phosphate (DOXP/MEP) pathway.
AB  - Higher plants, several algae, bacteria, some strains of Streptomyces and possibly
      malaria parasite Plasmodium falciparum contain the novel, plastidic DOXP/MEP
      pathway for isoprenoid biosynthesis. This pathway, alternative with respect to
      the classical mevalonate pathway, starts with condensation of pyruvate and
      glyceraldehyde-3-phosphate which yields 1-deoxy-D-xylulose 5-phosphate (DOXP);
      the latter product can be converted to isopentenyl diphosphate (IPP) and
      eventually to isoprenoids or thiamine and pyridoxal. Subsequent reactions of this
      pathway involve transformation of DOXP to 2-C-methyl-D-erythritol 4-phosphate
      (MEP) which after condensation with CTP forms 4-diphosphocytidyl-2-amethyl-D
      erythritol (CDP-ME). Then CDP-ME is phosphorylated to 4-diphosphocytidyl-2
      amethyl-D-erythritol 2-phosphate (CDP-ME2P) and to 2-C-methyl-D-erythritol-2,4
      cyclodiphosphate (ME-2,4cPP) which is the last known intermediate of the DOXP/MEP
      pathway. For- mation of IPP and dimethylallyl diphosphate (DMAPP) from ME-2,4cPP
      still requires clarification. This novel pathway appears to be involved in
      biosynthesis of carotenoids, phytol (side chain of chlorophylls), isoprene, mono
      , di-, tetraterpenes and plastoquinone whereas the mevalonate pathway is
      responsible for formation of sterols, sesquiterpenes and triterpenes. Several
      isoprenoids were found to be of mixed origin suggesting that some exchange and/or
      cooperation exists between these two pathways of different biosynthetic origin.
      Contradictory results described below could indicate that these two pathways are
      operating under different physiological conditions of the cell and are dependent
      on the developmental state of plastids.

PMID- 11833776
TI  - Effect of aluminium on plant growth and metabolism.
AB  - Aluminium toxicity is one of the major factors that limit plant growth and
      development in many acid soils. Root cells plasma membrane, particularly of the
      root apex, seems to be a major target of Al toxicity. However, strong interaction
      of Al3+, the main Al toxic form, with oxygen donor ligands (proteins, nucleic
      acids, polysaccharides) results in the inhibition of cell division, cell
      extension, and transport. Although the identification of Al tolerance genes is
      under way, the mechanism of their expression remains obscure.

PMID- 11833777
TI  - Antioxidative defense to lead stress in subcellular compartments of pea root
      cells.
AB  - Lead, similar to other heavy metals and abiotic factors, causes many unfavorable
      changes at the subcellular and molecular levels in plant cells. An increased
      level of superoxide anion in Pisum sativum root cells treated with 1 mM Pb(NO3)2
      evidenced oxidative stress conditions. We found increased activities of enzymatic
      components of the antioxidative system (catalase and superoxide dismutase) in the
      cytosol, mitochondrial and peroxisomal fractions isolated from root cells of
      Pisum sativum grown in modified Hoagland medium in the presence of lead ions (0.5
      or 1 mM). Two isoenzyme forms of superoxide dismutase (Cu,Zn-SOD and Mn-SOD)
      found in different subcellular compartments of pea roots were more active in Pb
      treated plants than in control. Increased amount of alternative oxidase
      accompanied by an increased activity of this enzyme was found in mitochondria
      isolated from lead-treated roots. These results show that plants storing
      excessive amounts of lead in roots defend themselves against the harmful
      oxidative stress caused by this heavy metal.

PMID- 11833778
TI  - Cloning and characterization of Arabidopsis thaliana AtNAP57--a homologue of
      yeast pseudouridine synthase Cbf5p.
AB  - Rat Nap57 and its yeast homologue Cbf5p are pseudouridine synthases involved in
      rRNA biogenesis, localized in the nucleolus. These proteins, together with H/ACA
      class of snoRNAs compose snoRNP particles, in which snoRNA guides the synthase to
      direct site-specific pseudouridylation of rRNA. In this paper we present an
      Arabidopsis thaliana protein that is highly homologous to Cbf5p (72% identity and
      85% homology) and NAP57 (67% identity and 81% homology). Moreover, the plant
      protein has conserved structural motifs that are characteristic features of
      pseudouridine synthases of the TruB class. We have named the cloned and
      characterized protein AtNAP57 (Arabidopsis thaliana homologue of NAP57). AtNAP57
      is a 565 amino-acid protein and its calculated molecular mass is 63 kDa. The
      protein is encoded by a single copy gene located on chromosome 3 of the A.
      thaliana genome. Interestingly, the AtNAP57 gene does not contain any introns.
      Mutations in the human DKC1 gene encoding dyskerin (human homologue of yeast
      Cbf5p and rat NAP57) cause dyskeratosis congenita a rare inherited bone marrow
      failure syndrome characterized by abnormal skin pigmentation, nail dystrophy and
      mucosal leukoplakia.

PMID- 11833779
TI  - Differences in editing of mitochondrial nad3 transcripts from CMS and fertile
      carrots.
AB  - A high level of the nucleotide sequence conservation was found for mitochondrial
      nad3 gene of carrot. Three silent nucleotide substitutions differentiate nad3
      open reading frames from cytoplasmic male sterile and male fertile carrots. All
      these differences are preserved on the RNA level. Partial and silent editing also
      distinguished both carrots. Three of the C to U conversions were specific to the
      fertile line. In the two examined carrot lines editing did not affect the mode of
      alteration of encoded amino acids.

PMID- 11833780
TI  - The influence of depletion of voltage dependent anion selective channel on
      protein import into the yeast Saccharomyces cerevisiae mitochondria.
AB  - The supply of substrates to the respiratory chain as well as of other metabolites
      (e.g. ATP) into inner compartments of mitochondria is crucial to preprotein
      import into these organelles. Transport of the compounds across the outer
      mitochondrial membrane is enabled by mitochondrial porin, also known as the
      voltage-dependent anion-selective channel (VDAC). Our previous studies led to the
      conclusion that the transport of metabolites through the outer membrane of the
      yeast Saccharomyces cerevisiae mitochondria missing VDAC (now termed YVDAC1) is
      considerably restricted. Therefore we expected that depletion of YVDAC1 should
      also hamper protein import into the mutant mitochondria. We report here that
      YVDAC1-depleted mitochondria are able to import a fusion protein termed pSu9-DHFR
      in the amount comparable to that of wild type mitochondria, although over a
      considerably longer time. The rate of import of the fusion protein into YVDAC1
      depleted mitochondria is dis- tinctly lower than into wild type mitochondria
      probably due to restricted ATP access to the intermembrane space and is
      additionally influenced by the way the supporting respiratory substrates are
      transported through the outer membrane. In the presence of ethanol, diffusing
      freely through lipid membranes, YVDAC1-depleted mitochondria are able to import
      the fusion protein at a higher rate than in the presence of external NADH which
      is, like ATP, transported through the outer membrane by facilitated diffusion. It
      has been shown that transport of external NADH across the outer membrane of
      YVDAC1-depleted mitochondria is supported by the protein import machinery, i.e.
      the TOM complex (Kmita & Budzinska, 2000, Biochim. Biophys. Acta 1509, 86-94.).
      Since the TOM complex might also contribute to the permeability of the membrane
      to ATP, it seems possible that external NADH and ATP as well as the imported
      preprotein could compete with one another for the passage through the outer
      membrane in YVDAC1-depleted mitochondria.

PMID- 11833781
TI  - Effect of growth at low temperature on the alternative pathway respiration in
      Acanthamoeba castellanii mitochondria.
AB  - Mitochondria of amoeba Acanthamoeba castellanii in addition to the conventional
      cytochrome pathway possess, like plant mitochondria, a cyanide-resistant
      alternative quinol oxidase. In mitochondria isolated from amoeba batch culture
      grown temporarily at low temperature (6 degrees C), higher respiration was
      accompanied by lower coupling parameters as compared to control culture (grown at
      28 degrees C). In the presence of benzohydroxamate, respiratory rates and
      coupling parameters were similar in both types of mitochondria indicating that
      growth in cold conditions did not disturb the cytochrome pathway. Increased
      contribution of alternative oxidase in total mitochondrial respiration in low
      temperature-grown amoeba cells was confirmed by calculation of its contribution
      using ADP/O measurements. Furthermore, in mitochondria from low-temperature-
      grown cells the content of the alternative oxidase was increased and correlated
      with the increase in the unstimulated and GMP-stimulated cyanide-resistant
      respiratory activity. A possible physiological role of higher activity of
      alternative oxidase as response to growth at a low temperature in unicellular
      organisms, such as amoeba, is discussed.

PMID- 11833782
TI  - Inhibition of the helicase activity of HCV NTPase/helicase by 1-beta-D
      ribofuranosyl-1,2,4-triazole-3-carboxamide-5 '-triphosphate (ribavirin-TP).
AB  - In the presented study the ribavirin-TP--an established inhibitor of the NTPase
      activity of the superfamily NTPase/helicases II--was investigated as an inhibitor
      of the unwinding activity of the hepatitis C virus (HCV) NTPase/helicase. The
      kinetics of the reaction revealed that ribavirin-TP reduces the turnover number
      of the helicase reaction by a mechanism that does not correspond to that of the
      inhibition of the NTPase activity. Our results suggest that derivatives of
      ribavirin-TP with enhanced stability towards hydrolytic attack may be effective
      inhibitors of the enzyme.

PMID- 11833783
TI  - Expression level of adenosine kinase in rat tissues. Lack of phosphate effect on
      the enzyme activity.
AB  - In this report we describe cloning and expression of rat adenosine kinase (AK) in
      Esccherichaia coli cells as a fusion protein with 6xHis. The recombinant protein
      was purified and polyclonal antibodies to AK were generated in rabbits.
      Immunoblot analysis of extracts obtained from various rat tissues revealed two
      protein bands reactive with anti-AK IgG. The apparent molecular mass of these
      bands was 48 and 38 kDa in rat kidney, liver, spleen, brain, and lung. In heart
      and muscle the proteins that react with AK antibodies have the molecular masses
      of 48 and 40.5 kDa. In order to assess the relative AK mRNA level in rat tissues
      we used the multiplex PCR technique with beta-actin mRNA as a reference. We found
      the highest level of AK mRNA in the liver, which decreased in the order kidney >
      spleen > lung > heart > brain > muscle. Measurement of AK activity in cytosolic
      fractions of rat tissues showed the highest activity in the liver (0.58 U/g),
      which decreased in the order kidney > spleen > lung > brain > heart > skeletal
      muscle. Kinetic studies on recombinant AK as well as on AK in the cytosolic
      fraction of various rat tissues showed that this enzyme is not affected by
      phosphate ions. The data presented indicate that in the rat tissues investigated
      at least two isoforms of adenosine kinase are expressed, and that the expression
      of the AK gene appears to have some degree of tissue specificity.

PMID- 11833784
TI  - Effect of tartaric acid on conformation and stability of human prostatic
      phosphatase: an infrared spectroscopic and calorimetric study.
AB  - The solution structure and thermal stability of human prostatic acid phosphatase
      (hPAP) in the absence and in the presence of tartaric acid were studied by
      Fourier transform infrared spectroscopy (FTIR) and differential scanning
      calorimetry (DSC). The temperature dependence of the infrared spectrum and DSC
      scans indicate that hPAP undergoes thermal unfolding at a temperature between
      49.5 and 52.5 degrees C. Binding of tartaric acid does not lead to major changes
      in the secondary structure of hPAP, however, hPAP with bound tartaric acid shows
      a significantly increased thermal stability. These results helped to better
      understand the mechanism of hPAP unfolding at the elevated temperature.

PMID- 11833785
TI  - Purification and characterization of alpha-amylases from the intestine and muscle
      of ascaris suum (Nematoda).
AB  - Alpha-Amylase (EC 3.2.1.1) was purified from the muscle and intestine of the
      parasitic helminth of pigs Ascaris suum. The enzymes from the two sources
      differed in their properties. Isoelectric focusing revealed one form of a-amylase
      from muscles with pl of 5.0, and two forms of amylase from intestine with pI of
      4.7 and 4.5. SDS/PAGE suggested a molecular mass of 83 kDa and 73 kDa for
      isoenzymes of a-amylases from intestine and 59 kDa for the muscle enzyme. Alpha
      Amylase from intestine showed maximum activity at pH 7.4, and the enzyme from
      muscle at pH 8.2. The muscle enzyme was more thermostabile than the intestinal
      alpha-amylase. Both the muscle and intestine amylase lost half of its activity
      after 15 min at 70 degrees C and 50 degrees C, respectively. The Km values were:
      for muscle amylase 0.22 microg/ml glycogen and 3.33 microg/ml starch, and for
      intestine amylase 1.77 microg/ml glycogen and 0.48 microg/ml starch. Both
      amylases were activated by Ca2+ and inhibited by EDTA, iodoacetic acid, p
      chloromercuribenzoate and the inhibitor of a-amylase from wheat. No significant
      differences were found between the properties of a-amylases from parasites and
      from their hosts.

PMID- 11833786
TI  - Cytochrome P4502C9 genotype in Southeast Anatolia and possible relation with some
      serum tumour markers and cytokines.
AB  - Substrates for CYP2C9 include fluoxetine, phenytoin, warfarin, losartam and
      numerous nonsteroidal anti-inflammatory drugs. Polymorphisms in the coding region
      of the CYP2C9 gene produce variants at amino-acid residues 144 Arg/Cys and 359
      Ile/Leu of the CYP2C9 protein. Individuals homozygous for Leu359 have markedly
      diminished metabolic capacities for most CYP2C9 substrates, the frequency of this
      allele is, however, rather low. Consistently with the modulation of enzyme
      activity by genetic and other factors, wide interindividual variability occurs in
      the elimination and/or dosage requirements of prototypic CYP2C9 substrates. The
      polymorphic enzyme CYP2C9 takes part in the metabolism of alkylating agents and
      polycyclic aromatic hydrocarbons like benzo(a)pyrene, a carcinogen present in
      tobacco smoke. Although the impact of impaired enzyme activity in metabolism of
      carcinogens and procarcinogens has not been fully defined, an association of
      CYP2C9 variant alleles to DNA adduct levels in lung tissues as well as to lung
      cancer risk have been reported. In this study 64 healthy subjects (44M/22F) were
      analysed for CYP2C9 genotype with PCR-RFLP and for serum carcinoembryonic antigen
      (CEA), alpha-fetoprotein (AFP), CA 19-9, CA 15-3, ferritin, IL-6, IL-8
      concentrations by chemiluminescence or electrochemiluminescence methods. CYP2C9*1
      was found to be the most prevalent allele and CYP2C9*1/CYP2C9*1 was the most
      frequent genotype represented in 64% of the population in southeastern Anatolia
      (Gaziantep). Although slight differences in serum tumour marker and cytokine
      concentrations were observed for CYP2C9 genotypes the differences were
      statistically insignificant (P > 0.05). This could be due to the complexity of
      the role of CYP2C9 in benzo(a)pyrene metabolism as well as from other
      contributing factors like interindividual variability of diverse enzymes
      participating in the same metabolic pathway, unequal expression of the variant
      alleles and differences in exposure to carcinogens. However, determination of
      CYP2C9 phenotypes in a larger group of subjects might clarify these slight
      differences.

PMID- 11833787
TI  - Comparative studies of nuclear DNA content in benign and malignant thyroid
      lesions.
AB  - Currently available data suggest that DNA aneuploidy is associated with
      aggressive behavior of and unfavorable prognosis in several malignant human
      tumors as compared with diploid malignancies. However, the diagnostic and
      prognostic importance of flow cytometric DNA measurements in the case of thyroid
      neoplasms remains controversial. Therefore, the aim of our study was to evaluate
      utility of DNA index (DI) and proliferative index (PI) in distinguishing benign
      from malignant thyroid lesions taking into account the possible influence of
      intra-tumor heterogeneity and tissue preparation mode on DNA flow-cytometry
      measurements. A retrospective study was performed on 71 paraffin-embedded
      specimens from 57 patients with benign and malignant thyroid pathologies: 13
      colloid goitres, 12 parenchymatous goitres, 19 adenomas and 13 carcinomas. In 14
      of 57 cases two separate specimens taken from different areas of the same lesion
      were analysed and DNA parameters were compared. Additionally, flow cytometry DNA
      analysis was parallelly performed on 3 adjacent but differently processed tissue
      sections (fresh, formalin-fixed and paraffin-embedded) taken from each of 26
      surgically excised thyroid lesions. DNA content was also analysed in both fresh
      and formalin-fixed twin specimens of normal pig thyroid glands (N = 6). We
      demonstrated that all tumors diagnosed as thyroid carcinomas were associated with
      abnormal nuclear DNA content although aneuploidy was not found specific to
      malignant thyroid tumors. Aneuploid samples of benign thyroid lesions exhibited
      higher proliferative activity, expressed as mean PI values, than diploid ones. In
      carcinomas the mean PI values were significantly higher than in benign lesions,
      independently whether they concerned aneuploid or diploid tissues. Considering
      intra-tumor heterogeneity, the flow cytometric DNA parameters can be assumed as
      reproducible despite differences in the mode of tissue fixation and preparation
      for analysis.

PMID- 11833788
TI  - Direct in vivo transfer of plasmid DNA into murine tumors: effects of endotoxin
      presence and transgene localization.
AB  - The purpose of this study was to investigate the effect of endotoxin presence in
      plasmid DNA preparations on the efficiency of transfection achieved in vivo with
      B16(F10) and Renca tumors and to determine transgene localization. Our data show
      that endotoxin markedly decreases the efficiency of transfection. Furthermore,
      the transgene transferred in vivo can be found in both neoplastic and normal
      (most likely myofibroblast) cells lying in proximity of the administration site.

PMID- 11833789
TI  - A new era for SETAC: the challenges of globalization. Society of Environmental
      Toxicology and Chemistry.

PMID- 11833790
TI  - Air-water exchange of polycyclic aromatic hydrocarbons in the New York-New
      Jersey, USA, Harbor Estuary.
AB  - Polycyclic aromatic hydrocarbons (PAHs, n = 36) were measured in the gas and
      particle phases in the atmosphere and the dissolved and particle phases in the
      waters of the New York-New Jersey Harbor Estuary, USA, during a weeklong
      intensive field campaign in July 1998. Mean total (gas + particulate)
      phenanthrene and pyrene concentrations were 3.3 and 0.33 ng/m3, respectively,
      over Raritan Bay, and 14 and 1.1 ng/ml, respectively, over New York Harbor.
      Similar PAH profiles (p values < 0.01) in the atmospheric gas phase and the
      dissolved phase in water demonstrate the close coupling of the air and water
      compartments. Air-water exchange fluxes of PAHs estimated using shore-based air
      data lead to erroneous flux estimates when compared to those derived using over
      water air samples. The gross absorptive air-water flux dominates atmospheric
      loadings (wet, dry particle, gas absorption) to the estuary for PAHs of molecular
      weight < 234 g/mol. Dry particle deposition is increasingly more important for
      the higher-molecular-weight, particle-bound PAH species. Gross volatilization
      dominates gross absorption for the majority of PAHs in the New York-New Jersey
      Harbor Estuary.

PMID- 11833791
TI  - Sources and distribution of polychlorinated dibenzo-p-dioxins and dibenzofurans
      in sediments from Masan Bay, Korea.
AB  - Polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDDs/DFs) were measured in
      sediments collected from Masan Bay, Korea. Almost all tetra- through
      octachlorinated PCDDs/DFs were identified, including the 17 2,3,7,8-substituted
      PCDDs/DFs. Total concentrations of PCDDs/DFs in sediments ranged from 102 to
      6,493 pg/g dry weight. Concentrations of 2,3,7,8-tetrachlorinated dibenzo-p
      dioxin (TeCDD) equivalents (TEQs) in sediments estimated based on I-TEFs were in
      the range of 1 to 76 pg/g dry weight. Total concentrations of PCDDs/DFs in Masan
      Bay sediments were comparable to those reported for the Rhine and Humber Rivers
      on the North Sea, the Housatonic River in the United States, and some rivers and
      lakes in Japan and the United Kingdom. A spatial gradient of total concentrations
      of PCDDs/DFs decreased toward the open sea. Two of the 11 sampling sites near the
      coastal zone contained relatively great concentrations, suggesting the presence
      of point sources. The homologue composition of PCDFs in sediments from two highly
      contaminated locations in Masan Bay was correlated with that of commercial
      polychlorinated biphenyl (PCB) preparations, such as Kanechlors 300, 400, or 500.
      The wide range of PCDD isomers and greater concentrations of PCDDs than of PCDFs
      at certain locations suggest that, in addition to technical PCB preparations such
      as Kanechlors, other sources, like solid waste incineration, uncontrolled trash
      burning, and pentachlorophenol, have contributed to the contamination.

PMID- 11833792
TI  - The effect of polycyclic aromatic hydrocarbons on the degradation of
      benzo[a]pyrene by Mycobacterium sp. strain RJGII-135.
AB  - Mycobacterium sp. strain RJGII-135 is capable of degrading a wide range of
      polycyclic aromatic hydrocarbons (PAHs), including benzo[a]pyrene (BaP). In this
      study, critical aspects of degradation were investigated, including compound
      uptake, relative rates of PAH degradation, and the effects of co-occurring PAH
      substrates on BaP degradation and mineralization to CO2. Mycobacterium sp. strain
      RJGII-135 was capable of degrading phenanthrene, anthracene, and pyrene at a 10-
      to 20-fold greater rate than benz[a]anthracene (BaA) and BaP. A significant
      amount of phenanthrene and pyrene, 30% and 10%, respectively, was completely
      mineralized, whereas less than 4% of anthracene, BaA, and BaP was mineralized.
      The PAH uptake assays demonstrated that high amounts of BaP and BaA, 81% and 75%
      of added compound, respectively, could be recovered from bacterial cell fractions
      after a 4-h incubation compared with pyrene (61%), anthracene (53%), and
      phenanthrene (47%). The half-saturation constant (Km) for pyrene was threefold
      lower for pyrene over BaP, suggesting that the degradation system in
      Mycobacterium sp. strain RJGII-135 has a higher affinity for pyrene, reaching
      maximal degradative activity at lower concentrations. No hybridization to
      dioxygenase gene probes nahAc, bphA1, or tolC1C2 was detected. Studies to
      investigate competition between different PAH substrates demonstrated that the
      rate of BaP metabolism was influenced by the presence of a second PAH substrate.
      The BaP metabolism was inhibited when coincubated with BaA, pyrene, and
      anthracene. Phenanthrene did not inhibit but enhanced BaP metabolism sixfold.
      These data suggest that induction effects of components of complex mixtures may
      be as important as competitive metabolism when assessing the ability of bacteria
      to effectively degrade high-molecular-weight PAHs in the environment.

PMID- 11833794
TI  - Phytoxicity of smelter-impacted soils in southwest Montana, USA.
AB  - A century of copper smelting in southwest Montana, USA, destroyed vegetation for
      many kilometers surrounding the Washoe Smelter. Once the vegetation was lost,
      exposed soils were subject to wind and water erosion, which removed topsoil and
      left soil surfaces paved with gravel. A greenhouse study was conducted using
      soils from smelter-impacted and non-smelter-impacted sites near Anaconda,
      Montana. Bluebunch wheatgrass, Agropyron spicatum (Pursh) Scribn., and western
      yarrow, Achillea lanulosa Nutt., were grown for 50 d in unamended, fertilized, or
      limed treatments to determine if soil fertility, pH, or trace elements were
      limiting plant growth on soil from the impacted site. The addition of fertilizer
      significantly increased plant biomass of both species in soils from impacted and
      nonimpacted sites when compared to unamended and limed soil. The addition of lime
      had no effect on plant growth. When plant growth in fertilized smelter-impacted
      soil was compared to unamended nonimpacted soil, significantly more plant biomass
      was observed in the fertilized smelter-impacted soil. Shoot and root
      concentrations of trace elements were higher in plants grown in impacted soil
      compared to nonimpacted soil. The only element that was found to occur in
      concentrations reported to be phytotoxic was arsenic (As). However, toxicity
      thresholds for As, reported in the literature, were generated in agricultural
      species and do not likely have application to the native perennials used in this
      study.

PMID- 11833793
TI  - Persistence and retention of active ingredients in four granular cholinesterase
      inhibiting insecticides in agricultural soils of the lower Fraser River valley,
      British Columbia, Canada, with implications for wildlife poisoning.
AB  - The persistence and retention of active ingredients in granules of Thimet 15G
      (phorate 15% by weight), Dyfonate 10G (fonofos 10% by weight), Counter 15G
      (terbufos 15% by weight), and Furadan 10G (carbofuran 10% by weight) were
      determined in silt loam and organic muck agricultural soils typical of the lower
      Fraser River valley (BC, Canada). In June 1995, treatment bags made of polyester
      cloth (7.5 x 7.5 cm) containing granules of a single insecticide, either alone or
      with soil, were placed during spring planting in the bottom of the furrow and
      retrieved periodically until April 1996. The parent component of each insecticide
      declined monotonically except for carbofuran (logistic decline). In the silt loam
      (organic muck) soil, the average June-to-October first-order rate constants and
      half-lives were 0.009 (0.010)/d and 80 (71) d for fonofos, 0.012 (0.009)/d and 58
      (82) d for phorate, and 0.032 (0.015)/d and 21 (47) d for terbufos; the half-life
      of carbofuran was 129 (97) d. By December, the average amounts of fonofos and
      phorate in silt loam (organic muck) were 26% (range: 17-40%; 14% [range: 3.4
      21%]) and 21% (range: 15-30%; 10% [range: 5.0-24%]) of the initial amounts of
      active ingredients measured at time zero, respectively. By April, the percentages
      dropped to 16% (range: 7.8-24%; 2.3% [range: 0-7.7%]) and 7.3% (range: 1.9-25%;
      0.6% [range: 0-1.9%]). During this period, about 95% of the active ingredients
      were granule bound, the rest remaining in the bag. Only low levels of terbufos
      and carbofuran persisted in both soils from December to April of the following
      year. Results indicate an enhanced probability for poisoning of waterfowl and
      raptors because of the high levels of active ingredients retained on granules of
      all four insecticides in both soils in the fall. The risk of acute poisoning by
      phorate and fonofos continued though the winter.

PMID- 11833795
TI  - Speciation of copper in sewage effluents and its toxicity to Daphnia magna.
AB  - Copper complexation capacity was determined in a range of sewage treatment works
      final effluents and receiving waters, upstream and downstream of the discharge
      point. Forty-eight-hour immobilization tests on Daphnia magna were used to assess
      the toxicity of copper in the effluent matrix. Complexation capacities in
      effluents were typically in the range 50 to 100 microg Cu/L, with higher values
      being found in the poorer-quality effluents with higher dissolved organic carbon
      (DOC) concentrations. The tolerance of Daphnia to dissolved copper concentrations
      was more than quadrupled in a 50% effluent matrix, with the increase in tolerance
      being related to complexation capacity. Ligand concentrations in effluents were
      found to correlate strongly with effluent DOC. No such relationship was observed
      in surface waters. On mixing with river water, sewage-derived ligands behaved
      conservatively and were relatively stable over time scales of up to 10 d.

PMID- 11833796
TI  - Cycling of weathered chlordane residues in the environment: compositional and
      chiral profiles in contiguous soil, vegetation, and air compartments.
AB  - Technical chlordane, a synthetic organic pesticide composed of 147 separate
      components, some of which exhibit optical activity, was used as an insecticide,
      herbicide, and termiticide prior to all uses being banned in the United States in
      1988. It has been shown that food crops grown in soil treated decades earlier
      with technical chlordane translocate the weathered chlordane residues from the
      soil into root and aerial plant tissues. A rigorous analytical method is
      presented for the simultaneous, quantitative determination of both achiral and
      chiral components of technical chlordane in soil, plant, and air compartments
      using chiral gas chromatography interfaced to ion trap mass spectrometry and
      internal standard calibration. Using this method, we have observed differences in
      both the absolute and the relative amounts of trans- and cis-chlordane
      enantiomers and achiral trans-nonachlor between the soil compartment and various
      plant tissue compartments for several field-grown food crops. Changes in the
      relative amounts of the (+) and (-) enantiomers of trans- and cis-chlordane
      indicate enantioselective processes are in effect in the contiguous compartments
      of soil, plant roots, and aerial plant tissues. The data for zucchini (Cucurbita
      pepo L.), in particular, show an approximate fivefold enhancement in absolute
      concentration for total trans-chlordane, an eightfold concentration enhancement
      for total cis-chlordane, and a 2.5-fold enhancement for trans-nonachlor in the
      root relative to the soil matrix, the largest enhancements of any crop studied.
      This is the first comprehensive report of enantioselective processes into and
      through plant tissues for a variety of field-grown food crops. The selectivity
      will be related to observed insect toxicities of the enantiomers.

PMID- 11833797
TI  - Optimizing interpretation of in situ effects of riverine pollutants: impact of
      upwelling and downwelling.
AB  - In situ toxicity and bioaccumulation tests with Ceriodaphnia dubia (48 h),
      Chironomus tentans (96 h), Hyalella azteca (96 h), and Lumbriculus variegatus (96
      h) were conducted at three stations on a river that was contaminated primarily
      with chlorobenzenes (CBs), and results were compared to a nearby reference site.
      Exposures were characterized by using minipiezometers for contaminant profiling
      and determination of hydraulic heads and vertical flow direction within the
      sediments and measuring contaminants in sediment, surface water, and exposure
      chamber water samples. Localized zones of upwelling and downwelling existed in
      the exposure areas at contaminated sites 5 and 18, while site 23 was downwelling
      at all measurement positions. Pore-water samples from minipiezometers contained
      CBs at the three contaminated sites that were highest at site 23. However,
      sediment and water samples from exposure chambers at site 23 contained the lowest
      levels of CBs among the contaminated sites. The CBs were not detected at the
      reference site, but other organic contaminants and metals were detected at all
      sites, with the highest concentrations occurring at sites 5 and 18. In water
      column exposures, no significant (p > 0.05) differences were observed in species
      survival between the contaminated sites and the reference. Mean percentage
      survival of H. azteca, C. dubia, and C. tentans exposed to surficial sediments
      (SS) at sites 5 and 18 was significantly (p < 0.05) reduced compared to the
      reference, whereas only C. tentans survival was significantly reduced at site 23.
      Body residues of total CB congeners in L. variegatus exposed to SS were highest
      at site 18 (618 micromol/kg lipid) and lowest at site 23 (21 micromol/kg lipid).
      The data suggest that downwelling reduced the bioavailability of CBs in surficial
      sediments, most likely by mobilizing the freely dissolved and colloid-bound
      fractions to deeper sediments. Overall, downwelling conditions reduced the in
      situ exposure of organisms in surficial sediments and hence the toxicity and
      bioaccumulation of CBs. Hydrologic and chemistry data from nested minipiezometers
      improved the interpretation of exposure-effects relationships.

PMID- 11833798
TI  - A pesticide surface water mobility index and its relationship with concentrations
      in agricultural drainage watersheds.
AB  - An index to benchmark pesticide mobility relevant to surface water runoff and
      soil erosion (surface water mobility index, or SWMI) was derived based on two key
      environmental fate parameters: degradation half-life and organic carbon
      normalized soil/water sorption coefficient (Koc). Values assigned with the index
      of each individual compound correlate well with the concentration trend of 13
      pesticides monitored in six Lake Erie, USA, tributaries from 1983 to 1991.
      Regression using a power function of SWMI fits concentration data well at various
      percentiles in the database for each tributary and all six tributaries combined,
      with r2 ranging from 0.71 to 0.94 for the concentrations at the 95th percentile.
      Good agreement was also obtained between SWMI and the time-weighted annual mean
      concentrations (r2 = 0.67-0.87). Although concentrations at or near peaks tend to
      be driven by rare hydrological events (intense precipitation immediately after
      application), SWMI explains the peak concentration data generally well (r2 = 0.53
      0.86). The SWMI-concentration relationship was further evaluated with two other
      pesticide monitoring databases: the U.S. Geological Survey National Water Quality
      Assessment Program White River Study Unit (1991-1996) at Hazelton, Indiana, USA,
      and the Syngenta (previously Novartis) Voluntary Monitoring Program with
      Community Water Systems at the Higginsville City Lake, Missouri, USA (1995-1997).
      The ability of the proposed SWMI to discriminate pesticide runoff mobility and
      its correlation with surface water monitoring data can be significant in the
      development of screening methodologies and data-based models for government
      agencies and/or practitioners in general facing increasing pressure to assess
      pesticide occurrence in aquatic environments.

PMID- 11833799
TI  - Mutagenicity and disinfection by-products in surface drinking water disinfected
      with peracetic acid.
AB  - The aims of this research were to study the influence of peracetic acid (PAA) on
      the formation of mutagens in surface waters used for human consumption and to
      assess its potential application for the disinfection of drinking water. The
      results obtained using PAA were compared to those found with sodium hypochlorite
      (NaClO) and chlorine dioxide (ClO2). The Ames test, root anaphase aberration
      assay, and root/micronuclei assay in Allium cepa and Tradescantia/micronuclei
      test were used to evaluate the mutagenicity of disinfected samples.
      Microbiological tests were also performed, and disinfection by-products (DBPs)
      were identified using gas chromatography/mass spectrometry (GC/MS). A slight
      bacterial mutagenicity was found in raw lake and river water, and similar
      activity was detected in disinfected samples. A plant test revealed genotoxicity
      in raw river water, and microbiological analysis showed that PAA has bactericidal
      activity but lower than that of the other disinfectants. The DBPs produced by PAA
      were mainly carboxylic acids, which are not recognized as mutagenic, whereas the
      waters treated with the other disinfectants showed the presence of
      mutagenic/carcinogenic halogenated DBPs. However, additional experiments should
      be performed with higher concentrations of PAA and using water with higher
      organic carbon content to better evaluate this disinfectant.

PMID- 11833800
TI  - Utility of a juvenile fathead minnow screening assay for detecting (anti
      )estrogenic substances.
AB  - The European Chemical Industry's aquatic research program for endocrine
      disrupters includes the development of an in vivo juvenile fathead minnow
      (Pimephales promelas) screening assay. Working within the Organization for
      Economic Cooperation and Development's (OECD, Paris, France) tiered approach to
      endocrine disrupter evaluation in fish, the juvenile fish screening protocol was
      adapted from the OECD test guideline 204. Six chemicals, with different (anti
      )estrogenic potencies, were used to develop the in vivo juvenile fish screening
      protocol: diethylstilbestrol, 17alpha-ethynylestradiol, genistein, methoxychlor,
      4-tert-pentylphenol, and ZM189,154 (a novel pharmaceutical antiestrogen). Mixed
      sex juvenile fathead minnows were exposed to individual chemicals (with chemical
      analyzes) and sampled after 4, 7, 14, and 21 d of exposure. Wet weight, total
      length, condition factor, and whole-body homogenate concentrations of
      vitellogenin (VTG) were determined. Estrogens and antiestrogens were detected in
      this screen by virtue of the VTG response (an elevation or suppression,
      respectively) after 14 d. The study showed that the use of VTG concentrations in
      mixed-sex juvenile fish provides a sensitive and robust assay for the detection
      of both estrogenic and antiestrogenic chemicals, with widely divergent potencies.

PMID- 11833801
TI  - Relationship between feeding-induced ventilatory activity and bioaccumulation of
      dissolved and algal-bound cadmium in the Asiatic clam Corbicula fluminea.
AB  - The influence of feeding-induced ventilatory adaptation on cadmium accumulation
      patterns was analyzed in quiescent Asiatic clam Corbicula fluminea studied in
      steady-state conditions at 15 degrees C and 25 degrees C and in air-equilibrated
      water. Ventilatory activity, algae inflow rate, amounts of inspired dissolved and
      algae-bound Cd, and whole-body and tissue-specific metal concentrations were
      studied during a 15-d exposure period at a low dissolved cadmium concentration of
      2 microg/L and various algal concentrations of Scenedesmus subspicatus. Great
      care was taken not to externally stimulate animals. Four main results were
      obtained as regard to regulation of ventilatory activity and metal accumulation
      rate. First, at 25 degrees C, feeding purposes strongly stimulated ventilatory
      activity, while at 15 degrees C, it was independent of it except at 1 to 2 x
      10(5) algae/ml. Second, Cd accumulation rate increased at higher temperature.
      Third, accumulation rate exhibited a positive correlation with the ventilatory
      flow rate. Fourth, no correlation was observed with the quantity of ventilated
      algae-bound Cd but, rather, with the quantity of ventilated dissolved Cd. It is
      concluded that the physiology of the animals can be fundamental in affecting
      metal accumulation process.

PMID- 11833803
TI  - Does status of attachment influence survival time of zebra mussel, Dreissena
      polymorpha, exposed to chlorination?
AB  - Mussels colonize cooling water circuits of power stations by attaching themselves
      to the pipe or conduit walls using byssus threads. Once manually detached, they
      quickly try to reattach by producing new byssus threads. In many published
      reports on antifouling bioassays, the test specimens are exposed to the biocide
      in an unattached state. These mussels, while trying to reattach, are likely to
      expose themselves more frequently to the toxic compound when compared to firmly
      attached mussels. The results of the assay, therefore, could vary, depending on
      the status of the mussels used. In this paper, we test the hypothesis that the
      status of attachment could influence the toxicity response of mussels and show
      that byssally attached zebra mussel, Dreissena polymorpha (Pallas), is more
      resistant to chlorine than unattached ones. An average increase of 27% in the
      survival time was observed for attached mussels over unattached ones in the
      chlorine concentration range of 0.25 to 3 mg/L. It is conclusively shown that the
      increase in sensitivity of the unattached mussels was related to an increase in
      the byssal activity, quantified presently as the byssogenesis index. The results
      indicate that future laboratory toxicity experiments involving mussels should be
      carried out using byssally attached ones.

PMID- 11833802
TI  - Preferential biomagnification of aryl hydrocarbon hydroxylase-inducing
      polychlorinated biphenyl congeners in the Lake Michigan, USA, lower food web.
AB  - Preferential biomagnification of 14 dioxin-like polychlorinated biphenyls (PCBs)
      was determined in lower-trophic-level organisms of the Lake Michigan, USA, food
      web. Bioaccumulation of these coplanar, aryl hydrocarbon hydroxylase (AHH)
      inducing PCB congeners and total PCBs in phytoplankton, zooplankton, Mysis
      relicta, and Diporeia sp. were studied for two locations in Lake Michigan over
      time. The results indicate that both total PCB and AHH-inducing PCBs biomagnify
      with increasing food web trophic level, with biomagnification of the AHH-inducing
      PCBs occurring to a greater degree. The biomagnification factors (BMFs) of the
      AHH-inducing PCBs suggest that they are highly conserved relative to other PCB
      congeners. The concentrations expressed as dioxin toxic equivalencies (TEQ
      concentrations) indicate that the biomagnification of AHH PCBs causes greater
      concentrations, and thus greater toxicity risk, with increasing trophic level.

PMID- 11833804
TI  - The effect of calcium and magnesium ratios on the toxicity of copper to five
      aquatic species in freshwater.
AB  - While it is generally accepted that water hardness affects copper toxicity, the
      major ions that contribute to water hardness (calcium [Ca] and magnesium [Mg])
      may affect copper toxicity differently. This is important because the Ca:Mg ratio
      in standard laboratory-reconstituted waters often differs from the ratio in
      natural surface waters. Copper toxicity was assessed for five different aquatic
      species: rainbow trout (RBT), fathead minnow (FHM), Ceriodaphnia dubia, Daphnia
      magna, and an amphipod (Gammarus sp.) under different Ca:Mg ratios (4:0, 3:1,
      1:1, 1:3, and 1:4 mass basis) at a common hardness (180 mg/L as CaCO3) and
      alkalinity (120 mg/L as CaCO3). Copper toxicity increased at lower Ca:Mg ratios
      for RBT but increased at higher Ca:Mg ratios for D. magna. Fathead minnows (<24 h
      old) were more sensitive to copper in 1:1 Ca:Mg waters compared to 3:1 Ca:Mg
      waters. The toxicity of copper did not vary under different Ca:Mg ratios for
      Gammarus sp., C. dubia, and 28-d-old FHM. The effect of Ca:Mg ratios on copper
      toxicity changed for D. magna in softer water (90 mg/L as CaCO3) compared with
      hard water studies.

PMID- 11833805
TI  - Effects of agricultural runoff on native amphibians in the Lower Fraser River
      Valley, British Columbia, Canada.
AB  - Hatching success, deformity rates, and survivorship of northern red-legged frogs
      (Rana aurora) and northwestern salamanders (Ambystoma gracile) were assessed at
      three agricultural and three reference sites in the Sumas Prairie, British
      Columbia, Canada. In 1997 and 1998, eggs of both species and eggs of R. aurora,
      respectively, were placed in Nytex mesh cages (Irwindale, CA, USA) in roadside
      ditches at each site. Concurrently in 1997, eggs of R. aurora were reared in the
      laboratory but were exposed to water samples from each of the study sites.
      Hatching success was significantly lower at all agricultural sites compared to
      the reference sites for both species. However, no differences were observed in
      hatching success among sites for eggs of R. aurora reared in the laboratory.
      Water chemistry differed among all sites, but the largest differences were
      between reference and agricultural sites. Ammonia (maximum of 1.27 mg/L), total
      phosphate (maximum of 8.14 mg/L), and biological oxygen demand (maximum of 79.00
      mg/L) were high at some of the agricultural sites during the development period.
      Results suggest that agricultural runoff may contribute to lower reproductive
      success and ultimately to reduced population viability of amphibian populations
      in the Lower Fraser Valley (BC, Canada).

PMID- 11833806
TI  - Evaluation of the Gammarus pulex in situ feeding assay as a biomonitor of water
      quality: robustness, responsiveness, and relevance.
AB  - Biomonitoring using benthic macroinvertebrates has been used to assess water
      quality in Europe since the early 20th century. Most methods use community-level
      measurements, and the use of single-species responses has been limited, despite
      their potential benefits as sensitive, early warning indicators. Here we evaluate
      a single-species in situ assay in which the response is feeding inhibition of the
      freshwater amphipod Gammarus pulex. The assay was deployed in uncontaminated
      reference sites to quantify background variability in feeding rates and to
      elucidate sources of this variation. The ability of the assay to detect impacts
      of point-source discharges was assessed and the ecological relevance of the assay
      determined by comparing assay responses to aspects of community structure and
      functioning. Water temperature accounted for 76% of the variation in the feeding
      rate of animals deployed at uncontaminated sites, and summer deployments had a
      >90% power to detect a 30% inhibition in feeding. Inhibition of the situ feeding
      rate of G. pulex deployed downstream of a variety of point-source discharges
      ranged from 27 to 99.6%. Gammarus pulex is an important detritivore in stream
      communities, and a strong positive correlation existed between in situ feeding
      rate measured over 6 d and leaf decomposition measured over 28 d. A positive
      correlation also existed between in situ feeding and macroinvertebrate diversity
      and a biotic index. The G. pulex in situ feeding assay is a short-term sublethal
      biomonitor of water quality that is indicative of community- and ecosystem-level
      responses occurring over longer time periods. It is robust, responsive, and
      relevant.

PMID- 11833807
TI  - Physiological responses to acute silver exposure in the freshwater crayfish
      (Cambarus diogenes diogenes)--a model invertebrate?
AB  - Adult crayfish (Cambarus diogenes diogenes) exposed to 8.41 +/- 0.17 microg
      silver/L (19.4% as Ag+) in moderately hard freshwater under flow-through
      conditions for 96 h exhibited ionoregulatory disturbance, elevated metabolic
      ammonia (T(amm)) production and substantial silver accumulation in the gills,
      hemolymph, and hepatopancreas. The ionoregulatory disturbance included both a
      generally reduced unidirectional Na+ influx and an increased unidirectional Na+
      efflux, leading to a substantial net loss of Na+ from the silver-exposed
      crayfish. The Na+ uptake in silver-exposed crayfish differed overall from
      controls, while the increased Na+ efflux recovered to control values 48 h into
      the 96 h of exposure. The general inhibition of Na+ uptake could be explained by
      a reduced sodium/potassium-adenosine triphosphatase (Na/K-ATPase) activity in
      terminally obtained gill samples from the silver-exposed crayfish. The silver
      induced effect on Na+ uptake and loss translated to reduced hemolymph Na+
      concentrations but not significantly reduced hemolymph Cl- concentrations.
      Hemolymph T(anim) and T(amm) efflux both increased in silver-exposed crayfish,
      indicating an increased metabolic T(amm) production. The present study
      demonstrates that the toxic mechanism of waterborne silver exposure in freshwater
      crayfish resembles that of freshwater teleost fish. The crayfish might therefore
      be a useful model system for extending current environmental regulatory
      strategies, currently based on teleost fish, to invertebrates.

PMID- 11833808
TI  - Developmental disorders in embryos of the frog Xenopus laevis induced by
      chloroacetanilide herbicides and their degradation products.
AB  - Pesticides are known to transform in the environment, but so far the study of
      their effects in the environment has concentrated on the parent compounds,
      thereby neglecting the effects of the degradation products. The embryotoxic,
      developmental, and teratogenic effects of chloroacetanilide herbicides and their
      environmentally stable aniline degradation products were investigated in this
      study in view of the massive application of alachlor and metolachlor. Embryos at
      midblastula to early gastrula stages of a locally abundant African clawed frog
      Xenopus laevis were used as test organisms. The embryos were exposed to the test
      chemicals for 96 h in each experiment. Alachlor is more embryotoxic (the
      concentration causing 50% embryo lethality, 96-h LC50 = 23 microM [6.1 mg/L]) and
      teratogenic (teratogenic index [TI] = 1.7) than metolachlor (96-h LC50 = 48
      microM [13.6 mg/L], TI = 0.2). The degradation products of alachlor and
      metolachlor, respectively, 2,6-diethylaniline (96-h LC50 = 13 microM [19.4 mg/L],
      TI = 2.1) and 2-ethyl-6-methyaniline (96-h LC50 = 509 microM [68.8 mg/L], TI =
      2.7), are less embryotoxic but more teratogenic than their parent compounds. The
      most common teratogenic effects observed were edema for alachlor as opposed to
      axial flexures and eye abnormalities for 2,6-diethylaniline and 2-ethyl-6
      methylaniline. Metolachlor is found to be an example of a nonteratogenic
      herbicide that upon degradation loses toxicity but gains teratogenicity, and both
      the herbicides, metolachlor and alachlor, are potential sources of teratogenic
      transformation products.

PMID- 11833809
TI  - A temperate reef fish, Tautogolabrus adspersus, (Walbaum) as a potential model
      species for laboratory studies evaluating reproductive effects of chemical
      exposure.
AB  - In ecotoxicological testing, there are few studies that report on reproductive
      output (egg production) of marine or estuarine fish. Cunner (Tautogolabrus
      adspersus) were studied as a potential model species to evaluate the impact of
      pollutants with estrogenic activity on reproduction in estuarine fish
      populations. Cunner inhabit marine and estuarine areas where contaminant
      discharges are likely. Baseline values for cunner gonadosomatic index (GSI),
      hepatosomatic index (HSI), and plasma vitellogenin (VTG) were determined in a
      field reference site (April 1999-December 1999). Male and female GSI indicated
      that cunner spawning is synchronized. Female HSI and VTG increased prior to GSI.
      From our laboratory observations, cunner are suitable for conducting experiments
      with reproductive endpoints indicative of both exposure (vitellogenin levels) and
      effects (egg production). However, cunner are not sexually dimorphic and
      stripping ripe fish is the only method to distinguish sex. In preparation for
      laboratory exposure studies with cunner, we designed a laboratory experimental
      holding system to accommodate cunner's reproductive behavior, a vertical spawning
      run to the water surface. Cunner were successfully acclimated from overwintering
      torpor to spawning condition in the laboratory by gradually changing the
      environmental conditions of fish held at winter conditions (4 degrees C and 9:15
      h light:dark photoperiod) to spawning condition (18 degrees C and 15:9-h
      light:dark photoperiod). Our results show that cunner successfully spawned daily
      in the laboratory. They produced fertile eggs in our experimental system designed
      to accommodate cunner's vertical spawning runs, demonstrating that male and
      female reproductive behavior was synchronized in the laboratory. Our observations
      indicate that cunner would be a useful model species for evaluating reproductive
      effects of environmental contaminants in laboratory studies.

PMID- 11833810
TI  - Analysis of hepatic vitamins A1, A2, their fatty acyl esters, and vitamin E for
      biomonitoring mammals feeding on freshwater fish.
AB  - In tissues of freshwater fish-feeding mammals, 3,4-didehydroretinol (A2) is a
      major form of vitamin A. In mink liver, with organochlorine exposure, this analog
      has been found to decrease more than retinol (A1) and thus has potential as a
      sensitive freshwater biomarker. The presence of the analogs A1 and A2 as alcohol
      and different fatty acyl esters, which react to polychlorinated biphenyls
      differently, necessitates detailed analyses achieved by using direct extraction
      of tissue homogenate. In direct hexane extraction, compared to total levels of
      the vitamins obtained in the saponification procedure, a large proportion of the
      vitamins was released only after repeated and long-time vortex mixing with the
      extraction solvent. Thus, in tissue extraction, the use of internal
      standardization alone can lead to a rough underestimation of the levels of these
      fat-soluble vitamins. For analyses of vitamins A1 and A2 in liver, we applied the
      argentation high-performance liquid chromatography, which provided good
      separation of individual A1 and A2 fatty acyl esters. We report retention times
      for numerous esters of A1 and A2 and, to aid identification, the change in their
      retention properties after adding AgNO3 to the mobile phase. The argentation did
      not affect the recoveries of any forms of the retinoids studied but destroyed
      half the vitamin E. Despite selective acylation of fatty acids into the vitamin A
      esters, the fatty acids of the esters were the same as those found to be the
      major fatty acids in the gas-liquid chromatography of total lipids. The goal of
      this work was to create a methodology that is suitable for biomonitoring
      alcoholic and esterified vitamins A1 and A2 in tissues of freshwater fish-feeding
      mammals.

PMID- 11833811
TI  - Vitamins A1 and A2 in hepatic tissue and subcellular fractions in mink feeding on
      fish-based diets and exposed to Aroclor 1242.
AB  - Two-month-old female mink were fed diets based on either Baltic herring (Clupea
      harengus membras) or freshwater smelt (Osmerus eperlanus) for 21 weeks. A portion
      of the smelt-fed mink were exposed orally to polychlorinated biphenyls (PCBs),
      Aroclor 1242 (1 mg/d). Retinol (vitamin A1), 3,4-didehydroretinol (vitamin A2),
      and their different fatty acyl esters were studied in hepatic tissue, microsomes,
      and cytosol by argentated reversed-phase high-performance liquid chromatography.
      As a result of Aroclor exposure, concentrations of the fatty acyl esters of
      vitamins A1 and A2 were about one-tenth and those of unesterified A2 one-fourth
      those of the control levels. In the fatty acyl esters, percentages of stearates
      (A1--18:0 and A2--18:0) increased at the expense of the other fatty acyl esters.
      The Aroclor exposure decreased concentrations of alcoholic and esterified forms
      of the A2 analog more than those of the corresponding A1 analog. In microsomes.
      Aroclor decreased the alcoholic and esterified vitamin analogs to the same extent
      (to 9-17%). In the cytosol compared to the control, the concentrations of the
      vitamin esters fell below 10%, but the alcoholic analogs remained at 30 to 40%.
      Despite equal dietary supply, in mink fed on Baltic herring, the hepatic levels
      of vitamin A, were only about one-third of the values found in the smelt-fed
      mink. The organochlorines also altered hepatic lipid composition and impaired
      breeding and kit growth. In the kits of the females fed on Baltic herring, blood
      hemoglobin was decreased.

PMID- 11833812
TI  - Environmentally relevant concentrations of ammonium perchlorate inhibit
      development and metamorphosis in Xenopus laevis.
AB  - We determined whether environmentally relevant concentrations of ammonium
      perchlorate alter development and metamorphosis in Xenopus laevis. Eggs and
      larvae were exposed to varying concentrations of ammonium perchlorate or control
      medium for 70 d. Most treatment-related mortality was observed within 5 d after
      exposure and was due in large part to reduced hatching success. The 5- and 70-d
      median lethal concentrations (LC50s) were 510 +/- 36 mg ammonium perchlorate/L
      and 223 +/- 13 mg ammonium perchlorate/L, respectively. Ammonium perchlorate did
      not cause any concentration-related developmental abnormalities at concentrations
      below the 70-d LC50. Ammonium perchlorate inhibited metamorphosis in a
      concentration-dependent manner as evident from effects on forelimb emergence,
      tail resorption, and hindlimb growth. These effects were observed after exposure
      to ammonium perchlorate concentrations in the parts-per-billion range, at or
      below concentrations reported in surface waters contaminated with ammonium
      perchlorate. Ammonium perchlorate significantly inhibited tail resorption after a
      14-d exposure in the U.S. Environmental Protection Agency (U.S. EPA) Endocrine
      Disruptor Screening and Testing Committee (EDSTAC) Tier I frog metamorphosis
      assay for thyroid disruption in amphibians. We believe that ammonium perchlorate
      may pose a threat to normal development and growth in natural amphibian
      populations.

PMID- 11833813
TI  - Comparing the acute response to cadmium toxicity of nauplii from different
      populations of Artemia.
AB  - The lethal responses to cadmium of instar II nauplii from eight populations of
      Artemia belonging to the species Artemia franciscana, Artemia salina, Artemia
      persimilis, and Artemia parthenogenetica have been compared. Generalized linear
      models were used to fit mortality. The model indicates that there is a
      relationship between species, type of population, and mortality rate. The two
      populations of A. franciscana were the most sensitive to cadmium toxicity (median
      lethal concentration, LC50, of 93.3-142 mg/L), while the population of A.
      persimilis was the most resistant (LC50 of 284 mg/L). Differences in the
      phenotypic variability in each population were assessed through the slope of the
      mortality curve, with A. persimilis exhibiting the highest diversity. This study
      suggests that habitat peculiarities and historical origin of the populations may
      have a significant influence on their response to cadmium toxicity.

PMID- 11833814
TI  - Population responses of the freshwater amphipod Gammarus pulex (L.) to an
      environmental estrogen, 17alpha-ethinylestradiol.
AB  - The effects of the environmental estrogen 17alpha-ethinylestradiol (EE) on mixed
      populations of 90 individual Gammarus pulex were examined following a 100-d
      exposure in a flow-through system. Counts of total animal numbers revealed that,
      in all treatment groups, population size dramatically increased due to
      recruitment, with neonate and juvenile gammarids the most abundant. At
      concentrations of 1 and 10 microg/L EE, the recorded mean population sizes of 385
      and 411, respectively, were significantly greater (p = 0.018) than the control
      (169). Mean population sizes in the solvent control (257) and 100 ng/L EE
      treatment (267) were not significantly different (p > 0.05) from the control. In
      addition to total counts, detailed image analysis of each individual animal
      allowed the assessment of length-frequency distributions, adult sex ratio, number
      of precopula pairs/ovigerous females, and measurement of secondary antenna and
      gnathopod length (secondary sex characteristics). The sex ratio of adults at 100
      ng, 1 microg, and 10 microg/L EE was greater than 2:1 (female:male), and
      significantly more females (p = 0.008) were recorded at these concentrations
      compared with the control. The number of male adults, precopula guarding pairs,
      and ovigerous females did not differ between treatments (p > 0.05). Secondary
      antennal and gnathopod length in males was consistently greater than in females
      (p < or = 0.001), but comparison between groups revealed no difference in these
      parameters.

PMID- 11833815
TI  - A cautionary note on the use of species presence and absence data in deriving
      sediment criteria.
AB  - In recent years, a variety of approaches to deriving sediment quality guidelines
      have been developed. One approach relies on establishing an empirical
      relationship between the concentration of a contaminant in sediment and the
      condition of some biological indicator, for example, combining measured sediment
      concentrations of contaminants combined with data on colocated benthic species to
      measure in situ community effects of contamination. Biological threshold
      concentrations derived in this manner are being considered or have already been
      adopted by some regulatory agencies as a means for deriving sediment guidelines
      (e.g., Canada's Provincial Sediment Quality Guidelines). In order to test the
      validity of this method, we constructed several Monte Carlo simulations to
      illustrate that the methodology used to develop these guidelines is flawed by the
      effects of sampling and statistical artifacts that emerge from undersampling a
      lognormal density function. As a case study, this paper will present the
      screening level concentration method used by the Ontario Ministry of the
      Environment (Toronto, ON, Canada) and provide the results of several
      probabilistic exercises highlighting these issues. We present a word of caution
      on the applicability of methods that rely exclusively on statistical and
      mathematical relationships between invertebrate data and sediment concentrations
      to derive sediment quality guidelines.

PMID- 11833816
TI  - Cutaneous lymphosarcoma.

PMID- 11833817
TI  - Mask induction of anaesthesia with isoflurane or sevoflurane in premedicated
      cats.
AB  - A comparison was made of the time to and quality of induction of anaesthesia when
      sevoflurane (n=14) or isoflurane (n=14) was delivered by mask in premedicated
      healthy adult cats presented for elective surgery. Times to induction and
      intubation were significantly shorter with sevoflurane (210 +/- 57 seconds and
      236 +/- 60 seconds, respectively) than with isoflurane (264 +/- 75 seconds and
      292 +/- 73 seconds). The quality of induction was similar for both agents. Two
      cats in each group developed opisthotonus of less than 45 seconds' duration. Both
      sevoflurane and isoflurane produced mask induction of anaesthesia of a similar
      quality in this species. Sevoflurane provided more rapid induction of anaesthesia
      and establishment of a controlled airway than isoflurane.

PMID- 11833818
TI  - Partial atrioventricular canal defect in a dog.
AB  - A case of a partial atrial canal defect is described in a nine-month-old female
      English setter. The patient had a large ostium primum atrial septal defect and a
      concurrent malformation of the mitral valve. Electrocardiographic and
      radiographic findings were suggestive of marked enlargement of the right heart
      and pulmonary overcirculation. Definitive diagnosis and assessment of the
      haemodynamic consequences were made using echocardiography. The magnitude of the
      left-to-right intracardiac shunt was estimated by measuring the pulmonary to
      systemic flow ratio (Qp/Qs) from Doppler-derived pulmonary and aortic blood flow.
      The results of this report suggest that dogs with a partial atrioventricular
      canal defect and concurrent mild mitral regurgitation may exhibit no clinical
      signs during the first years of life, even in cases with a Qp/Qs ratio of greater
      than 2.

PMID- 11833819
TI  - Morphometric assessment of the canine hip joint using the dorsal acetabular rim
      view and the centre-edge angle.
AB  - The dorsal acetabular rim (DAR) view of the hip joint can be used to assess the
      weightbearing portion of the acetabulum and the acetabular coverage, providing an
      adjunct to the conventional ventrodorsal (VD) view in the radiographic evaluation
      of hip dysplasia in the dog. A quantitative index of acetabular coverage in the
      DAR view, the acetabular slope (AS) angle, was originally proposed in 1990. The
      aim of the present study was to make a prospective, comparative assessment of a
      new parameter, the centre-edge (CE) angle, with the AS angle, for the evaluation
      of the acetabular coverage of the femoral head in the DAR view. The reliability
      and repeatability of the two parameters was assessed using the r(I) value of
      intraclass correlation coefficient (ICC) in a prospective study of 208 hip joints
      in large and giant breed dogs. An estimation of the added value of using the DAR
      view, compared with that of the VD standard view alone, was also assessed. The CE
      angle showed a higher r(I) value compared with the AS angle; in 26 per cent of
      hips of FCI classes A, B and C, the DAR view provided additional diagnostic
      information compared with the VD view, with respect to lateralisation and/or
      initial changes to the dorsal rim. It is concluded that the CE angle is more
      reliable than the AS angle in the evaluation of acetabular coverage, and that the
      DAR view provides valuable data compared with the VD view alone in the early
      stages of canine hip dysplasia.

PMID- 11833820
TI  - Canine dysautonomia: two clinical cases.
AB  - Two clinical cases of canine dysautonomia are described. Two young female
      neutered dogs were presented with clinical signs including vomiting, diarrhoea,
      faecal tenesmus, dysphagia and urinary retention. Decreased tear production, dry
      mucous membranes, bilateral Horner's syndrome, decreased anal sphincter tone and
      gastrointestinal hypomotility were also observed. Presumptive diagnoses of
      dysautonomia were made based on the clinical presentation and investigations.
      Postmortem histopathological examination in one of the cases demonstrated marked
      depletion of neuronal cell bodies in the intestinal myenteric plexuses and
      parasympathetic ganglia, confirming the diagnosis in this case. Criteria for
      aiding the antemortem diagnosis of this rare condition based on clinical
      observations and diagnostic testing are proposed.

PMID- 11833821
TI  - Development of hypertrophic osteodystrophy and antibody response in a litter of
      vaccinated Weimaraner puppies.
AB  - Two different vaccination protocols were compared with regard to the development
      of hypertrophic osteodystrophy (HOD) (also termed metaphyseal osteopathy) and
      effectiveness of immunisation in a litter of 10 Weimaraner puppies. Five puppies
      (group 1) were vaccinated with a modified live canine parvovirus vaccine (CPV)
      and then two weeks later with a trivalent vaccine containing modified live canine
      distemper virus and adenovirus type 2 combined with a Leptospira bacterin (DHL).
      The CPV and DHL vaccine protocols were administered a further two times, at two
      week intervals. Group 2 was vaccinated with three consecutive multivalent
      vaccines containing modified live canine distemper virus, canine parvovirus,
      parainfluenza and adenovirus type 2 combined with a Leptospira bacterin, at four
      week intervals. All puppies were first vaccinated at the age of eight weeks.
      Three dogs in group 1 developed HOD, while all five dogs in group 2 developed HOD
      during the study period. Dogs in group 2 had more episodes of HOD than those in
      group 1. Dogs in group 1 developed higher antibody titres to canine distemper
      virus and parvovirus compared with those in group 2. Only two out of the 10 dogs
      developed protective antibody titres to parvovirus. The results of this study
      suggest that the two different vaccination protocols affected the pattern of
      appearance of HOD and immunisation in this litter of Weimaraner puppies. The
      results obtained and the previously reported data suggest that a larger
      controlled study is needed to further elucidate the effect of different
      vaccination protocols on HOD and immunisation in Weimaraner puppies.

PMID- 11833822
TI  - Haematology and gastroenterology for the practitioner.

PMID- 11833823
TI  - A simplified technique for diagnostic and surgical arthroscopy of the shoulder
      joint in the dog.
AB  - A modified technique is presented for surgical and diagnostic arthroscopy of the
      shoulder joint in the dog. The technique involves access to the joint through two
      points only; one was created in place of the drainage needle-cannula, which was
      replaced with a portal, while the second was located more caudally compared with
      previous techniques. Using a changing guide rod system the two portals are
      completely interchangeable in order to perform easier arthroscopic surgery either
      in the cranial or caudal aspect of the joint. The presence of only one portal
      caudal to the lateral collateral ligament allows more freedom of movement and
      avoids interference between the arthroscope and the instruments. The modified
      procedure was performed on 33 joints affected by osteochondritis dissecans or
      tenoligament diseases and facilitated straightforward diagnostic examinations,
      and simple and rapid surgical procedures.

PMID- 11833824
TI  - A meta-analysis of the dose-response relationship of inhaled corticosteroids in
      adolescents and adults with mild to moderate persistent asthma.
AB  - BACKGROUND: Although inhaled corticosteroids (ICS) are commonly used in the
      treatment of persistent asthma, the relationship between dose and clinical
      response remains unclear. OBJECTIVE: This study investigated whether ICS exhibit
      a dose-response relationship in the treatment of mild to moderate persistent
      asthma. METHODS: This was a meta-analysis of published randomized clinical trials
      concerning the relationship between ICS dose and response in asthma. Relevant
      studies were identified through a search of PubMed and MEDLINE for articles on
      asthma and ICS published between January 1996 and January 2001. The search was
      limited to publications classified as clinical trials that included the text
      words asthma and corticosteroids, glucocorticoids, beclomethasone, budesonide,
      fluticasone, flunisolide, mometasone, or triamcinolone acetonide. Five clinical
      measures were considered: morning peak expiratory flow rate (AM PEFR), evening
      PEFR (PM PEFR), forced expiratory volume in 1 second (FEV(1)), beta-agonist use,
      and asthma symptom score (severity of symptoms on a given day, as evaluated by
      patients). RESULTS: Forty-three studies were identified, of which 16 met the
      criteria for inclusion in the meta-analysis. These studies involved 4 agents:
      fluticasone propionate, triamcinolone acetonide, budesonide, and mometasone
      furoate. A statistically significant dose response in AM PEFR was observed with
      fluticasone propionate, triamcinolone acetonide, and budesonide (respective 95%
      CIs, 4.9 to 11.5, 4.7 to 18.0, and 5.8 to 24.9). A statistically significant dose
      response to fluticasone propionate and triamcinolone acetonide was also observed
      in PM PEFR (95% CIs, 2.0 to 8.7 and 2.4 to 13.7) and asthma symptom score (95%
      CI, -0.069 to -0.002 and -0.60 to -0.10). In terms of FEV(1), the dose response
      was statistically significant only with budesonide (95% CI, 0.025 to 0.17). Dose
      response relationships were not disproportionately driven by the highest doses,
      and the greatest effects on response were seen at doses below or at the low end
      of the recommended range, suggesting that use of high doses of ICS may contribute
      only marginally to efficacy. CONCLUSIONS: Dose-response relationships were not
      uniformly observed with all drugs or for all measures of response. Use of higher
      doses of ICS in patients with mild to moderate persistent asthma does not appear
      to increase the efficacy of these drugs.

PMID- 11833825
TI  - An open-label comparison of the immunogenicity and tolerability of intranasal and
      intramuscular formulations of virosomal influenza vaccine in healthy adults.
AB  - BACKGROUND: Many intramuscular inactivated influenza vaccines achieve suboptimal
      results in the prevention of respiratory disease and influenza complications.
      This has led to the current interest in developing effective oral or intranasal
      preparations. OBJECTIVE: This study compared the immunogenicity and tolerability
      of intranasal and intramuscular formulations of virosomal subunit influenza
      vaccine in healthy adults. It also assessed the immunogenicity and tolerability
      of 3 different production lots of the intranasal vaccine containing Escherichia
      coli heat-labile toxin adjuvant. METHODS: This was a multicenter, Phase I,
      randomized, open-label pilot study in which the primary end point was
      immunogenicity (hemagglutination-inhibition [HI] antibody assay on days 1 and
      29). The secondary end point was the frequency of adverse events (AEs). Subjects
      were assigned to 4 vaccination groups: groups AI, AII, and AIII received
      intranasal influenza vaccine from batches that differed in the hemagglutinin and
      neuraminidase strains used, and group B received intramuscular virosomal subunit
      vaccine. Assessments of health status, hematology, biochemistry, body
      temperature, heart rate, blood pressure, and incidence of AEs were made on days
      1, 8, and 29, and serology was assessed on days 1 and 29. RESULTS: The study
      enrolled 88 subjects. All 3 production lots of intranasal vaccine induced an
      immune response to most of the viral strains administered (A/Singapore, A/Texas,
      A/Wuhan, B/Beijing), with no notable immunogenic differences between lots. After
      intranasal vaccination, geometric mean titers (GMT) increased 2.7-fold against
      A/Singapore (group AI); 1.8- and 3.1-fold against A/Texas (groups AII and AIII,
      respectively); 1.9- to 2.4-fold against A/Wuhan; and 1.5- to 1.7-fold against
      B/Beijing. After intramuscular vaccination. GMT increased 11.3-, 6.3-, and 2.7
      fold against A/Texas, A/Wuhan, and B/Beijing, respectively. Seroprotection (HI
      antibody titers > or = 1:40 in > 70% of those vaccinated) was achieved against
      all strains in the group that received intramuscular vaccination, against A/Wuhan
      in all groups that received intranasal vaccination, and against A/Texas in group
      AII. Both vaccine formulations were well tolerated. Intranasal vaccination was
      associated with a low incidence ( < 20%) of nasal AEs. CONCLUSIONS: Both the
      intranasal and intramuscular vaccinations elicited a systemic immune response and
      were well tolerated. The different batches of intranasal vaccine showed a similar
      immunogenic profile. Intranasal administration may be preferred to intramuscular
      administration by some patients.

PMID- 11833826
TI  - A multiple-dose pharmacodynamic, safety, and pharmacokinetic comparison of
      extended- and immediate-release formulations of lovastatin.
AB  - BACKGROUND: Because lovastatin is efficiently extracted by the liver and because
      its administration in divided doses is associated with increased efficacy, an
      extended-release (ER) formulation may have the potential for a dose-sparing
      advantage relative to the immediate-release (IR) formulation in the treatment of
      hypercholesterolemia. OBJECTIVE: This study compared the short-term
      pharmacodynamics, safety, and pharmacokinetics of multiple doses of lovastatin ER
      with those of lovastatin IR in patients with fasting low-density lipoprotein
      cholesterol (LDL-C) levels between 130 and 250 mg/dL and fasting triglyceride
      levels < 350 mg/dL. METHODS: The study had a randomized, single-blind, positive
      controlled, 2-way crossover design, with a 4-week diet/placebo run-in period and
      two 4-week active-treatment periods. During period 1, patients received either
      lovastatin ER or lovastatin IR (both 40 mg OD). After 4 weeks of the initial
      study treatment and a 2-week washout period, patients were switched to the
      alternate treatment (period 2). Pharmacodynamic parameters (LDL-C, high-density
      lipoprotein cholesterol, total cholesterol, and triglyceride levels) were
      evaluated by combining data from weeks 3 and 4 of treatment. In a pharmacokinetic
      substudy, maximum plasma concentrations (C(max)) and area under the plasma
      concentration-time curve from zero to 24 hours (AUC(024)) were determined for
      lovastatin, lovastatin acid, and total and active inhibitors of 3-hydroxy-3
      methylglutaryl coenzyme A (HMG-CoA) reductase on days 1 and 28 of active
      treatment. The geometric mean ratio of AUC(0-24) (lovastatin ER/lovastatin IR)
      was also calculated for each of these substances. RESULTS: Of 76 patients who
      entered the run-in period, 26 (12 men, 14 women; mean age, 56.2 years) were
      randomized to receive active treatment and 24 were included in the efficacy
      analysis; 13 patients were included in the pharmacokinetic substudy, 12 of whom
      had complete pharmacokinetic data. Compared with lovastatin IR, lovastatin ER
      produced a 3.9% greater reduction in LDL-C (P = 0.044). Changes in other lipid
      parameters were not statistically significant. In the pharmacokinetic substudy,
      C(max) values for lovastatin, lovastatin acid, and in hibitors of HMG-CoA
      reductase were lower at day 28 with lovastatin ER than with lovastatin IR. The
      AUC(0-24) ratio for lovastatin was 1.91 (90% CI, 1.77 - 3.35), reflecting higher
      bioavailability of the prodrug with lovastatin ER; in contrast, the ratios for
      lovastatin acid and active and total inhibitors of HMG-CoA reductase were < 1.
      CONCLUSIONS: In this short-term study in a small number of patients, lovastatin
      ER 40 mg produced significantly greater LDL-C lowering than did an equal dose of
      lovastatin IR, with a relatively low C(max) and comparable systemic exposure to
      lovastatin acid and active and total inhibitors of HMG-CoA reductase. Lovastatin
      ER was well tolerated, with no discontinuations due to adverse events.

PMID- 11833828
TI  - Our love affair with antibiotics: how will it end?

PMID- 11833827
TI  - A multicenter, randomized, double-blind comparison of the efficacy and safety of
      irbesartan and enalapril in adults with mild to moderate essential hypertension,
      as assessed by ambulatory blood pressure monitoring: the MAPAVEL Study
      (Monitorizacion Ambulatoria Presion Arterial APROVEL).
AB  - BACKGROUND: When blood pressure (BP)-lowering efficacy is assessed by
      measurements taken in a clinic setting, angiotensin II-receptor antagonists show
      similar efficacy to angiotensin-converting enzyme inhibitors and better
      tolerability. A search of MEDLINE to date, however, reveals no randomized, double
      blind studies using ambulatory BP monitoring (ABPM) to compare the BP-lowering
      efficacy of irbesartan and enalapril in a large number of patients ( > 200) with
      essential hypertension. OBJECTIVE: This study compared 24-hour BP reduction and
      BP control, as assessed by ABPM, in patients with mild to moderate essential
      hypertension treated with irbesartan or enalapril. The relative tolerability of
      the 2 treatments was also evaluated. METHODS: This was a multicenter, randomized,
      double-blind study in patients with mild to moderate essential hypertension
      (office diastolic BP [DBP] 90-109 mm Hg or systolic BP [SBP] 140-179 mm Hg).
      After a 3-week, single-blind placebo washout phase, patients with a mean daytime
      DBP > or = 85 mm Hg, as measured by ABPM between 10 AM and 8 PM, were randomized
      to 12 weeks of active treatment with irbesartan or enalapril. Starting doses were
      150 and 10 mg/d, respectively, with titration to 300 or 20 mg/d if clinic DBP was
      > or = 90 mm Hg at week 4 or 8. Based on clinic measurements, BP control was
      defined as a BP reading < 140/90 mm Hg after 12 weeks of treatment; patients
      achieving a reduction in DBP of > or = 10 mm Hg at 12 weeks were considered
      responders. The ABPM criterion for BP control, independent of clinic values, was
      achievement of a daytime BP < 130/85 mm Hg after 12 weeks of treatment; patients
      achieving a reduction in 24-hour DBP > or = 5 mm Hg at 12 weeks were considered
      responders, in dependent of clinic values. RESULTS: A total of 238 patients were
      randomized to treatment, 115 to irbesartan and 123 to enalapril. The study
      population was approximately 52.0% female and 48.0% male, with a mean ( +/- SD)
      age of 52.7 +/- 10.6 years. The study was completed by 111 patients in the
      irbesartan group (dose titrated to 300 mg/d in 72.0% of patients) and 115
      patients in the enalapril group (dose titrated to 20 mg/d in 76.5% of patients).
      BP reductions were similar in the 2 groups, both as measured in the clinic (DBP,
      12.7 +/- 8.8 mm Hg irbesartan vs 12.4 +/- 7.4 mm Hg enalapril; SBP, 19.0 +/- 14.1
      mm Hg vs 17.5 +/- 14.0 mm Hg) and by 24-hour ABPM (DBP, 9.4 +/- 8.5 mm Hg vs 8.8
      +/- 8.5 mm Hg: SBP, 14.7 +/- 14.7 mm Hg vs 12.6 +/- 13.1 mm Hg). As assessed by
      ABPM, rates of BP control were 40.5% (45/111) for irbesartan and 33.9% (39/115)
      for enalapril, and the response rates were a respective 71.2% (79/111) and 71.3%
      (82/115). The overall incidence of adverse events (40.0% irbesartan, 51.2%
      enalapril) was not statistically different between groups, although the incidence
      of adverse events considered probably related to antihypertensive treatment was
      significantly higher with enalapril than with irbesartan (24.6% vs 9.2%,
      respectively; P = 0.026), essentially because of the higher incidence of cough
      (8.1% vs 0.9%). CONCLUSIONS: As assessed by ABPM, irbesartan 150 to 300 mg/d was
      as effective in lowering BP and achieving BP control as enalapril 10 to 20 mg/d.
      Based on the number of treatment-related adverse events, irbesartan was better
      tolerated than enalapril.

PMID- 11833829
TI  - Health-related quality of life in patients treated for hypertension: a review of
      the literature from 1990 to 2000.
AB  - BACKGROUND: The goals of antihypertensive therapy are to achieve and maintain
      blood pressure control by the least intrusive means possible to prevent future
      cardiovascular and renal events. To achieve these goals, pharmacologic agents
      must be chosen so as to minimize drug-related adverse events, increase patient
      adherence to treatment regimens, and minimize the negative impact on health
      related quality of life (HRQL). Although the effects of antihypertensive therapy
      on HRQL have been extensively investigated, there is little synthesis of the
      research findings. OBJECTIVE: This review was undertaken to provide a synthesis
      of the available data on the impact of antihypertensive therapy on HRQL and to
      provide recommendations for future research. METHODS: A MEDLINE literature search
      was conducted to identify English-language articles published from 1990 to 2000
      that included random assignment to antihypertensive treatment and HRQL as an
      outcome. In addition, reference lists of published reviews and other trials were
      reviewed to identify other studies of HRQL and antihypertensive therapy. RESULTS:
      A total of 48 articles were included in the review. Results among studies were
      frequently inconsistent, which is likely due to the wide variety of dimensions
      studied and instruments used as well as a number of methodological weaknesses,
      including small sample sizes, short-term assessments, and failure to account for
      missing data. CONCLUSION: A standardized approach to the assessment of HRQL in
      hypertensive patients is needed so that research in this area can be of value to
      clinical practice and to hypertensive patients and their families.

PMID- 11833830
TI  - Antibiotic prescribing in ambulatory care settings for adults with colds, upper
      respiratory tract infections, and bronchitis.
AB  - BACKGROUND: Imprudent prescribing of antibiotics for patients with colds, upper
      respiratory tract infections (URIs), and bronchitis may contribute to antibiotic
      resistance and waste economic resources. OBJECTIVE: The purpose of this study was
      to determine the antibiotic prescribing rate for adults diagnosed with colds,
      URIs, and bronchitis in 1996 and to compare these rates with those reported for
      1992. METHODS: This was a retrospective, cross-sectional analysis of a US
      government data base of ambulatory physician practices. The number of adults ( >
      or = 18 years of age) with a diagnosis of cold, URI, or bronchitis and the
      percentage receiving antibiotics were determined from the 1996 National
      Ambulatory Medical Care Survey (NAMCS). The antibiotic prescribing rate was the
      main outcome measure. RESULTS: In 1996, approximately 13.9 million office visits
      resulted in a primary diagnosis of cold, URI, or acute bronchitis; of these
      visits, 46%, 47%, and 60%, respectively, resulted in the prescribing of an
      antibiotic. The respective rates in 1992 were 51%, 52%, and 66%. The rates of
      antibiotic prescribing were 12% to 16% higher when all drugs, not just the first
      drug listed in the NAMCS database, were analyzed. In 1996, antibiotic prescribing
      rates for persons 45 to 64 years of age and persons > 64 years of age were
      significantly lower than for those aged 18 to 44 years. CONCLUSIONS: The rates of
      potentially inappropriate antibiotic prescribing decreased modestly from 1992 to
      1996; however, previous rates may have been underestimated. The antibiotic
      prescribing rates for colds, URIs, and acute bronchitis may be as high as 61%,
      63%, and 72%, respectively, when all drug information is analyzed. Antibiotics
      are over-prescribed, which may increase antibiotic resistance and waste health
      care resources.

PMID- 11833831
TI  - A retrospective analysis of costs and patterns of treatment for external genital
      warts in The Netherlands.
AB  - BACKGROUND: External genital warts (EGWs) are one of the most common sexually
      transmitted infections, but little is known about the treatment patterns or
      resources used in the management of this condition. OBJECTIVE: The purpose of
      this retrospective analysis is to examine the patterns of treatment, resource
      utilization, and costs for EGWs in 3 dermatology clinics in the Netherlands.
      METHODS: A total of 530 completed episodes of care for EGWs were analyzed to
      identify patterns of treatment and resources used. Costs of care were calculated
      based on 4 cost components for each visit: labor costs, material costs, indirect
      costs, and extra costs. RESULTS: Across the 3 sites, men required an average of
      5.78 clinic visits to achieve a completed episode of care; women required an
      average of 6.52 visits. The distribution of visits is highly skewed, however,
      with a median of 4.56 visits for men and 5.55 for women. More than 80% of
      patients were initially treated with monotherapy. Podophyllin and cryotherapy
      were the principal choices for initial therapy. The mean cost, in euros, of
      completing an episode of care was 221.34 euro for men and 292.29 euro for women.
      The cost per completed or successful episode of care was 395.92 euro for men and
      485.05 euro for women. The distribution of costs was also skewed, with a
      relatively small group of patients accounting for a considerable proportion of
      overall costs. Although only 31.4% of male patients recorded > or = 6 visits for
      a completed episode of care, this group accounted for 57.3% of the total costs of
      treatment for male patients. Among female patients, 43.4% had > or = 6 visits,
      which accounted for 73.9% of the total costs of care for female patients. Costs
      also varied markedly by therapy sequence chosen. Patients who remained on their
      initial monotherapy or combination therapy had the lowest costs; the extent to
      which patients switched therapies substantially affected overall costs. For those
      patients initially treated with podophyllin, the mean total costs of treatment,
      taking into account the proportion who required a change in therapy, were 204.84
      euro for men and 386.38 euro for women. For those initially treated with
      cryotherapy, the mean cost of treatment was 193.60 euro for men and 169.23 euro
      for women. CONCLUSION: Current treatment options for EGWs do not appear to
      minimize resource utilization or help achieve complete episodes of care at the
      lowest possile cost.

PMID- 11833832
TI  - Injudicious antibiotic use: an unforeseen consequence of the emphasis on patient
      satisfaction?
AB  - BACKGROUND: Antibiotic resistance is an increasingly serious problem in the
      United States and many other parts of the world. One of the causes is the
      injudicious prescribing of antibiotics for self-limited viral infections.
      Physicians often cite parent and patient pressure as factors in their decisions
      to prescribe antibiotics for viral upper respiratory tract infections. OBJECTIVE:
      This article draws from the literature to determine the extent of patient and
      physician knowledge of appropriate antibiotic prescribing and to seek evidence
      for a link between antibiotic prescribing and patient satisfaction. Physician
      perception of patients' expectations regarding antibiotic use is also discussed.
      CONCLUSIONS: Both patients and physicians demonstrate poor knowledge regarding
      appropriate antibiotic prescribing for respiratory infections. Physicians are
      unable to judge patients' expectations accurately. Educational efforts aimed at
      both physicians and patients hold the most promise in decreasing unnecessary
      antibiotic use. These efforts include informing physicians that patient
      satisfaction is generally linked much more to communication than to the writing
      of a prescription.

PMID- 11833833
TI  - Effect of early telephone and postal reminders on medication compliance with
      pravastatin therapy.

PMID- 11833834
TI  - Ziprasidone: an atypical antipsychotic drug for the treatment of schizophrenia.
AB  - BACKGROUND: Over the past decade, use of the atypical antipsychotic drugs
      clozapine, risperidone, olanzapine, and quetiapine has significantly changed the
      treatment of schizophrenia in the United States. The ability to make optimal drug
      choices will depend on determining whether there are clinically important
      differences between these drugs. OBJECTIVE: This review describes ziprasidone,
      the most recently introduced antipsychotic drug. Its mechanism of action,
      pharmacokinetics, and adverse-effect profile are discussed, and the results of
      clinical efficacy trials are summarized. METHODS: This review of ziprasidone is
      based on data from premarketing clinical efficacy and safety trials, a briefing
      document from the US Food and Drug Administration Psychopharmacological Drugs
      Advisory Committee, published studies, and abstracts presented at national and
      international meetings. International Pharmaceutical Abstracts and MEDLINE were
      searched for relevant citations, with no limitation on year. RESULTS: Ziprasidone
      has been reported to be an effective antipsychotic drug for both positive and
      negative symptoms of schizophrenia, and long-term use has been effective in
      preventing relapse. Its 5-hydroxytryptamine (HT)1D-antagonist and 5-HT(1A)
      agonist activity are consistent with a potential for antidepressant and
      anxiolytic activity beyond its antipsychotic effects. Ziprasidone has been
      associated with a low incidence of sedative effects, a low likelihood of
      extrapyramidal symptoms and postural hypotension, and no anticholinergic effect,
      although it may cause transient hyperprolactinemia. Unlike most atypical
      antipsychotic drugs, ziprasidone is not associated with weight gain,
      hyperlipidemia, or elevated plasma glucose levels. It is, however, more likely
      than other atypical antipsychotic drugs to increase the QTc interval (QT interval
      corrected for heart rate). For acute psychotic symptoms in patients with
      schizophrenia, schizoaffective disorder, or acute mania, ziprasidone is
      administered twice daily at a usual daily dose of 80 to 160 mg, whereas 40 mg/d
      may be an effective maintenance dose. CONCLUSIONS: Differences in efficacy and
      tolerability between existing atypical antipsychotic drugs allow
      individualization of drug therapy for patients with schizophrenia or
      schizoaffective disorder. Ziprasidone differs from other atypical antipsychotic
      drugs in several clinically important ways, although further experience is
      necessary to clarify the significance of these differences.

PMID- 11833835
TI  - Bivalirudin: a direct thrombin inhibitor.
AB  - BACKGROUND: Studies of the anticoagulant effects of hirudin, which is derived
      from the saliva of the leech Hirudo medicinalis, led to the development of
      compounds that can directly inhibit thrombin activity without the need for
      additional cofactors. One of these is the direct thrombin inhibitor bivalirudin,
      which has recently been approved by the US Food and Drug Administration for use
      as an anticoagulant in patients with unstable angina undergoing percutaneous
      transluminal coronary angioplasty. OBJECTIVE: This is a review of the
      pharmacologic properties, efficacy, tolerability, and potential cost
      effectiveness of bivalirudin in the treatment of ischemic coronary syndromes.
      METHODS: Articles were identified by searches of MEDLINE (1966-September 2001),
      International Pharmaceutical Abstracts (1970-September 2001), and the Iowa Drug
      Information Service (1966-September 2001) using the terms bivalirudin and
      Hirulog. The reference lists of retrieved articles were also reviewed for
      relevant articles. RESULTS: Bivalirudin is a synthetic polypeptide that directly
      inhibits thrombin by binding simultaneously to its active catalytic site and its
      substrate recognition site. After intravenous administration, peak plasma
      concentrations occur in 2 minutes. In patients given a 1.0-mg/kg bolus followed
      by a 2.5-mg/kg per hour infusion, a median activated clotting time of 346 seconds
      is achieved with little interpatient or intrapatient variability. Clearance of
      bivalirudin occurs through a combination of renal elimination and proteolytic
      cleavage, and doses may need to be decreased in the presence of renal
      dysfunction. In patients undergoing percutaneous coronary interventions,
      bivalirudin has been associated with equivalent efficacy but lower bleeding rates
      (P < 0.001) than unfractionated heparin (UFH). Data from the Hirulog Early
      Reperfusion/Occlusion-2 study suggest no reduction in mortality with bivalirudin
      compared with heparin when either is added to aspirin and streptokinase in
      patients with acute myocardial infarction, despite a lower reinfarction rate (P <
      0.001). Experience with bivalirudin in patients with unstable angina and heparin
      induced thrombocytopenia (HIT), as well as in patients receiving glycoprotein
      IIb/IIIla inhibitors, is limited. The differences in bleeding rates between
      bivalirudin and heparin in published clinical trials probably reflect differences
      in levels of anticoagulation achieved in comparator groups. CONCLUSIONS: Given
      its high cost, bivalirudin should be reserved for use as an alternative to UFH,
      primarily in patients with HIT, until clinical trials have more clearly
      demonstrated its benefits in terms of efficacy or safety.

PMID- 11833836
TI  - Clinafloxacin versus piperacillin/tazobactam in the treatment of severe skin and
      soft-tissue infections in adults at a Veterans Affairs medical center.
AB  - BACKGROUND: Severe skin and soft-tissue infections (SSTIs), particularly diabetic
      foot infections, are a source of considerable morbidity and mortality.
      Inappropriate antimicrobial therapy may contribute to the increasing emergence of
      bacterial resistance, as well as to increased health care costs. Thus, there is a
      continuing search for reasonably safe, well-tolerated, and effective
      antimicrobial agents that are less susceptible to the development of resistance
      than older agents. OBJECTIVE: The Department of Veterans Affairs (VA) Medical
      Center in Nashville, Tennessee, was I site in a multicenter, Phase III,
      randomized, investigator-blinded clinical trial comparing the safety and efficacy
      of clinafloxacin with those of piperacillin/tazobactam in the treatment of adult
      patients with SSTI. METHODS: Over an 18-month period, patients aged > or = 18
      years with physical findings of acute bacterial SSTI requiring hospitalization
      and intravenous antimicrobial therapy were randomized in a 1:1 ratio to receive
      either clinafloxacin 200 mg IV every 12 hours or piperacillin/tazobactam 3.375 g
      IV every 6 hours. After a minimum of 3 days of intravenous therapy, a switch to
      oral therapy with clinafloxacin 200 mg PO every 12 hours or
      amoxicillin/clavulanate 500 mg PO every 8 hours could be made in the respective
      treatment groups. RESULTS: The center enrolled 84 patients (42 in each group),
      all but I of whom were male, reflecting the typical VA medical center population.
      The mean age was 60 years (range, 36-80 years) in the clinafloxacin group and 65
      years (range, 35-87) in the piperacillin/tazobactam group; the latter group was
      significantly older (P = 0.0482), which could have affected recovery rates. Sixty
      six patients were white and 18 were black. The mean ( +/- SD) duration of
      treatment was 10.69 +/- 5.34 days in the clinafloxacin group and 12.07 +/- 5.06
      days in the piperacillin/tazobactam group; the mean length of stay was 10.83 +/-
      10.28 days and 14.95 +/- 19.20 days, respectively. Fifty-three (63%) patients
      were switched to oral therapy (21 in the clinafloxacin group, 32 in the
      piperacillin/tazobactam group). The most commonly isolated pathogens were
      Staphylococcus aureus, Enterococcus faecalis, Pseudomonas aeruginosa, and
      Enterobacter cloacae. Clinical cure rates and microbiologic eradication rates
      were similar between the 2 treatments. The piperacillin/ tazobactam arm
      experienced more all-cause adverse events than the clinafloxacin arm, although
      the difference was not statistically significant. The clinafloxacin arm
      experienced significantly more adverse events (eg, photosensitivity) that were
      judged by the investigator to be drug related (P = 0.034). CONCLUSIONS: In this
      study population of hospitalized adults, clinafloxacin was as effective as
      piperacillin/tazobactam in the treatment of complicated SSTIs. Appropriate
      precautions must be taken against exposure to sunlight and ultraviolet light in
      patients receiving clinafloxacin, and adequate monitoring is necessary. Further
      investigation is necessary into how the phototoxic effects of the flu
      oroquinolones can be limited.

PMID- 11833837
TI  - Comparative efficacy of preprandial or postprandial Humalog Mix75/25 versus
      glyburide in patients 60 to 80 years of age with type 2 diabetes mellitus.
AB  - BACKGROUND: Humalog Mix75/25 (Mix75/25) is a novel premixed insulin containing
      75% neutral protamine lispro (an intermediate-acting insulin) and 25% insulin
      lispro. OBJECTIVE: The purpose of this study was to compare glycemic control and
      hypoglycemia rates with Mix75/25 versus glyburide, and with preprandial versus
      postprandial Mix75/25, in patients aged 60 to 80 years with type 2 diabetes
      mellitus and persistent hyperglycemia on sulfonylurea therapy. METHODS: In this
      open-label, 16-week, parallel-group study, patients were randomized to 1 of 2
      treatments: glyburide 15 mg/d (or up to the maximum daily dose) or Mix75/25. The
      Mix75/25 group was randomly subdivided into preprandial (immediately before
      breakfast and dinner) and postprandial (within 15 minutes after the start of
      breakfast and dinner) injection subgroups. The primary outcomes were glycemic
      control and rate of hypoglycemia. RESULTS: A total of 143 patients were
      randomized; 127 completed the study. The change in glycosylated hemoglobin
      (HbA(1c)) from baseline to end point was significantly greater with Mix75/25 than
      with glyburide (mean +/- SEM, -1.14% +/- 0.18% vs -0.36% +/- 0.15%, P = 0.001).
      HbA(1c) changes with preprandial and postprandial Mix75/25 were not significantly
      different (-1.20% +/- 0.26% vs -1.08% +/- 0.26%, P = 0.748). Fasting blood
      glucose (BG), 2-hour postprandial BG, and mean daily BG reductions were greater
      with Mix75/25 than with glyburide (P < 0.001); preprandial and postprandial
      Mix75/25 administration did not differ significantly with respect to any of these
      BG variables. The hypoglycemia rate increased with Mix75/25 by 0.17 +/- 0.02
      episodes per patient per 30 days, but there was no change with glyburide (P =
      0.077). Body weight increased by 1.02 +/- 0.35 kg with Mix75/25 and decreased by
      0.85 +/- 0.18 kg with glyburide (P < 0.001). CONCLUSIONS: Compared with
      glyburide, Mix75/25 significantly improved glycemic control in older patients
      with type 2 diabetes mellitus, could be administered after meals without
      compromising glycemic control, and was well tolerated.

PMID- 11833838
TI  - Combination hydrocodone and ibuprofen versus combination oxycodone and
      acetaminophen in the treatment of moderate or severe acute low back pain.
AB  - BACKGROUND: Introduced in 1997, the combination of hydrocodone and ibuprofen is
      the only fixed-dose combination analgesic containing an opioid and ibuprofen that
      has been approved by the US Food and Drug Administration. OBJECTIVE: This study
      compared the efficacy and tolerability of combination hydrocodone 7.5 mg and
      ibuprofen 200 mg (HC/IB) with those of combination oxycodone 5 mg and
      acetaminophen 325 mg (OX/AC) in the treatment of moderate or severe acute low
      back pain. METHODS: This was a multicenter, randomized, double-blind, parallel
      group, repeat-dose study lasting up to 8 days. The recommended dosing of the
      study medications was 1 tablet every 4 to 6 hours, not to exceed 5 tablets per
      day. If adequate pain relief was not obtained, patients were permitted to take up
      to 4 doses per day of supplemental analgesic medication-the nonopioid component
      of the assigned study medication (ibuprofen 200 mg or acetaminophen 325 mg).
      Measures of efficacy included mean daily pain relief scores (0 = no relief, 1 =
      slight relief, 2 = moderate relief, 3 = good relief, and 4 = complete relief),
      mean daily number of tablets and doses of study medication, mean daily number of
      tablets and doses of supplemental analgesic medication, global evaluation (poor,
      fair, good, very good, or excellent), and results on the modified 36-item Short
      Form Health Survey (SF-36). All efficacy measures were analyzed on an intent-to
      treat basis. Tolerability was evaluated based on adverse events reported
      spontaneously or elicited by the in vestigators using nonsuggestive questioning,
      as well as on the number of patients discontinuing treatment because of adverse
      events. RESULTS: The study enrolled 147 patients (75 HC/IB, 72 OX/AC). The most
      common cause of low back pain was muscular/ligamentous injury (97/147; 66.0%),
      followed by degenerative disk disease (27/147; 18.4%). At baseline, 80 patients
      (54.4%) reported experiencing moderate pain, and 67 patients (45.6%) reported
      experiencing severe pain. There were no significant differences between HC/IB and
      OX/AC with regard to mean ( +/- SD) daily pain relief scores (2.40 +/- 1.06 vs
      2.50 +/- 1.01, respectively), mean daily number of tablets of study medication
      (1.80 +/- 1.70 vs 2.20 +/- 1.60), mean daily number of doses of study medication
      (1.80 +/- 1.65 vs 2.10 +/- 1.58), mean daily number of tablets of supplemental
      analgesic medication (0.60 +/- 1.13 vs 0.50 +/- 0.99), mean daily number of doses
      of supplemental analgesic medication (0.60 +/- 1.07 vs 0.50 +/- 0.90), global
      evaluations, or mean scores on the modified SF-36. In addition, there were no
      significant differences in the proportion of patients experiencing adverse events
      with HC/IB (47; 62.7%) and OX/AC (45; 62.5%). Adverse events were consistent with
      those generally associated with the component analgesics and predominantly
      involved the central nervous system and gastrointestinal system. CONCLUSIONS: The
      results of this study suggest that HC/IB and OX/AC are similarly effective and
      tolerable in relieving moderate or severe acute low back pain. Additional
      controlled longitudinal trials are necessary to evaluate the clinical utility of
      HC/IB in treating acute low back pain.

PMID- 11833839
TI  - Serum lipoprotein(a) level in relation to severity of coronary artery disease and
      coronary artery patency in acute myocardial infarction.
AB  - Lipoprotein(a) (Lp(a)) is a low-density lipoprotein (LDL)-like particle that may
      accelerate atherogenesis and promote thrombosis. In the present study,
      relationships between serum Lp(a) levels and the severity of coronary artery
      disease and infarct artery patency were studied in 14 patients with acute
      myocardial infarction. Lp(a) was measured by enzyme-linked immunosorbent assay
      and the timing of reperfusion was evaluated using the creatine kinase myosin
      brain fraction and myoglobin release curves. Thrombolysis in Myocardial
      Infarction (TIMI) flow grade and severity of coronary artery disease were
      assessed using a scoring system based on coronary angiography performed during
      hospitalization and 6 months thereafter. The median Lp(a) level on admission was
      127 (range 11-2,513) mg/l. The overall coronary score was higher in patients with
      Lp(a) levels greater than 127mg/l than in those with Lp(a) less than 127mg/l (P <
      0.01). Lp(a) level correlated with the coronary score measured during
      hospitalization (r = 0.80, P < 0.01) and 6 months later (r = 0.79, P < 0.01). The
      timing of reperfusion and infarct artery patency were not depen dent on the serum
      Lp(a) level. The results show that the serum Lp(a) level is associated with the
      angiographic severity of coronary artery disease postmyocardial infarction bu
      does not determine the patency of the infarct-related artery.

PMID- 11833840
TI  - Measurement of aortic diameters and detection of asymptomatic aortic aneurysms in
      a mass screening program using a mobile helical computed tomography unit.
AB  - In a mass chest computed tomography (CT) screening using a mobile helical CT
      unit, we measured the aortic diameter at three segments to confirm standard
      values and also attempted to detect any asymptomatic aortic aneurysms. The
      population screened in the present study consisted of 6971 subjects (3847 men and
      3124 women, mean age 60.3 +/- 12.1 years). They underwent a plain chest CT to
      screen for lung cancer and tuberculosis. The diameters of the ascending and
      descending aorta were measured at the level of the pulmonary artery bifurcation.
      The abdominal aorta was measured at the level of the celiac bifurcation, and the
      mean values for each measurement were calculated. In addition, we attempted to
      determine whether any correlation exists among aortic diameter, age, and indices
      of body size and investigated the frequency of asymptomatic aortic aneurysms
      among the general population. The mean aortic diameter of all three segments was
      significantly larger in men than in women and increased with age. It also
      correlated significantly with indices of body size (P < 0.01). A total of 11
      subjects (0.16%) had asymptomatic aortic aneurysms (3 ascending, 4 descending,
      and 4 thoracoabdominal). The aortic diameter in each individual case was greater
      than the mean aortic diameter +3 standard deviations in each age group. Chest CT
      screening for lung cancer can thus detect asymptomatic aneurysms through
      simultaneous aortic measurement.

PMID- 11833841
TI  - Effect of homocysteine on the L-arginine/nitric oxide synthase/nitric oxide
      pathway in human platelets.
AB  - Recent evidence indicates that chronic hyperhomocysteinemia is an independent
      risk factor for the development of atherosclerosis, thrombosis, and other
      cardiovascular diseases. This may be secondary to impaired fibrinolysis, or
      increased platelet reactivity. L-Arginine/ nitric oxide synthase/nitric oxide
      (NO) plays an important role in the regulation of platelet function. The present
      study was undertaken to determine the effect of homocysteine (HCY) on the L
      arginine/NO pathway of human platelets. Washed human platelets were incubated in
      the presence or absence of HCY for 2h at 37 degrees C followed by a measurement
      of indices of the L-arginine/NO pathway. HCY caused a concentration-dependent
      reduction in the platelet uptake of L-[3H]arginine. HCY also caused a
      concentration-dependent decrease in nitrite production concurrent with a decrease
      in cyclic guanosine monophosphate, whereas NO synthase activity of the platelets,
      measured as conversion of L-[3H]arginine to L-[3H]citrulline, remained unchanged
      on incubation with HCY. These observations indicate that the L-arginine/NO
      pathway is involved in the mechanism responsible for the effects of HCY on
      platelets by diminishing NO production through decreased uptake of L-arginin

PMID- 11833842
TI  - Effects of long-term renal sympathetic denervation on heart failure after
      myocardial infarction in rats.
AB  - The purpose of the present study was to investigate the effects of long-term
      renal denervation (RD) on heart failure due to myocardial infarction (MI). Wistar
      rats were anesthetized and the bilateral renal nerves were surgically denervated
      2 days before MI was induced by coronary artery ligation. Four weeks later, left
      ventricular (LV) function and sodium excretion were determined. In MI rats, RD
      improved the reduced sodium excretion. MI + RD rats revealed lower LV end
      diastolic pressure and greater maximum dP/dt as compared with those of MI+
      innervation (INN) rats. LV end-diastolic and end-systolic dimensions were
      significantly smaller and LV fractional shortening was greater in MI + RD rats
      than in MI + INN rats (20.9% +/- 3.2% vs 14.9% +/- 3.0%). In rats without MI, RD
      did not affect either sodium excretion or LV function and dimensions. The present
      results suggest that the long-term RD reduces LV filling pressure and improves LV
      function after MI, probably due to a restoration of impaired natriuresis.
      Increased renal sympathetic nerve activity might contribute to the progression of
      heart failure after MI.

PMID- 11833843
TI  - Coronary and femoral arterial contraction with high glucose, insulin, and glucose
      insulin-potassium solution: effects of hypoxia.
AB  - We studied whether the contractile responses to potassium chloride (KCI) of rat
      coronary and femoral arteries differ when perfused with solutions containing
      varying concentrations of metabolic substrates (glucose, oxygen, insulin) and
      whether these differences might explain some of the beneficial effects of glucose
      insulin-potassium (GIK or polarizing) solution. We also studied the mediation of
      the endothelium on these effects. Contraction of femoral arteries decreased with
      low and high glucose while in coronary arteries it increased as the glucose
      concentrations rose. Endothelin receptor antagonists blocked this increase. The
      tension increase induced by insulin in both vessels was smaller in the coronary
      arteries. The ETA receptor antagonist PD51242 blocked most of the insulin effect
      in the coronary arteries, whereas in the femoral arteries this was blocked by the
      ET(B) receptor antagonist BQ788. Hypoxia blocked the constrictive responses to
      glucose and insulin of the coronary but not of the femoral arteries. GIK
      increased contractile force in hypoxic femoral arteries but reduced that in
      coronary arteries. The contractile response decreased by GIK in hypoxic coronary
      arteries was restored by N(G)-nitro-L-arginine methyl ester, suggesting mediation
      by nitric oxide. We conclude that in the presence of high glucose and/or insulin
      levels, coronary arteries respond to KCl differently from femoral arteries, their
      behavior during hypoxia might explain some of the beneficial effects of GIK.

PMID- 11833844
TI  - Effect of chronic hypoxia on contents of urotensin II and its functional
      receptors in rat myocardium.
AB  - The cyclic peptide urotensin II (UII) has recently been cloned in mammals and
      reported to constrict rat pulmonary arteries potently. An enhanced maximal
      response was shown in rats exposed to chronic hypoxia. The aim of this study was
      to investigate changes in plasma and myocardial UII levels and its receptor sites
      in crude sarcolemma of ventricles from chronic hypoxic rats. We observed that
      rats exposed to chronic hypoxia for 4 weeks developed pulmonary hypertension and
      right ventricular hypertrophy. Compared with controls, the UII content in hypoxic
      rats was increased by 97.5% (45.24 +/- 7.1 vs. 22.9 +/- 3.24pg/mg protein, P <
      0.01) in the right ventricle and 33.2% (24.89 +/- 0.99 vs. 18.68 +/- 2.04pg/mg
      protein, P < 0.01) in the left ventricle, respectively. However, there was no
      significant difference in plasma (27.44 +/- 3.11 vs. 27.82 +/- 5.57pg/ml, P >
      0.05) and lung tissue levels (34.03 +/- 4.63 vs. 33.74 +/- 4.06 pg/ mg protein, P
      > 0.05) between the control and hypoxic groups. The time course of the binding of
      [125I]UII to crude ventricular sarcolemma was specific and time dependent.
      Scatchard plot analysis of the data demonstrated that the maximal number of
      specific binding sites (Bmax) in both the right and left ventricles was
      upregulated in the hypoxic group. Moreover, Bmax in the right ventricular
      specimens was upregulated to a greater extent than in the left ventricle
      (increased by 114% and 25% in the right and left ventricles, respectively,
      compared with control group, P < 0.01). In contrast, the UII binding affinity in
      right and left ventricular membranes from hypoxic rats was decreased (the
      dissociation constant Kd) increased by 20% and 33%, respectively compared with
      controls, P < 0.01). These results indicate that UII may act as an autocrine
      and/or paracrine hormone rather than as a circulating hormone, playing important
      roles in the development of ventricular hypertrophy induced by chronic hypoxia,
      and that the pathophysiological significance of UII in pulmonary and
      cardiovascular alteration induced by chronic hypoxia deserves further
      investigation.

PMID- 11833845
TI  - Effects of milrinone for right ventricular failure after left ventricular assist
      device implantation.
AB  - Right ventricular failure after left ventricular assist device implantation
      sometimes requires additional mechanical right ventricular support. The
      effectiveness of nitrates, prostaglandin, or nitric oxide inhalation in such
      cases has already been reported. However, there are few reports on the
      administration of phosphodiesterase inhibitor for right ventricular failure after
      left ventricular assist device implantation. We report two patients with right
      ventricular failure after left ventricular assist device implantation
      successfully treated with milrinone. Both had residual pulmonary hypertension due
      to high pulmonary vascular resistance after left ventricular assist device
      implantation. However, intravenous milrinone caused a significant reduction in
      pulmonary vascular resistance and an increase in left ventricular assist device
      flow. Milrinone acts as both an inotropic agent and a direct vasodilator, and
      thus may avoid the need for mechanical support for right ventricular failure due
      to residual pulmonary hypertension after left ventricular assist device
      implantation.

PMID- 11833846
TI  - Subepicardial aneurysm after anticoagulant therapy for a mural thrombus following
      anterior myocardial infarction.
AB  - A subepicardial aneurysm became evident in a male patient after anticoagulant
      therapy. On admission, it appeared to be an old anterior infarction accompanied
      by a mural thrombus. After warfarin administration, the thrombus disappeared and
      an echo-free space emerged outside the apical myocardial wall. The echo-free
      space communicated with the left ventricular cavity through the apical myocardial
      wall. Emergency surgery was undertaken and the patient survived. The aneurysm was
      covered with epicardium and there was an endomyocardial rupture of the muscle in
      the apical wall, which was the entrance of the aneurysm. This case suggests that
      cautious follow-up with echocardiography is necessary when anticoagulant therapy
      is selected for thrombi following myocardial infarction.

PMID- 11833847
TI  - True aneurysm originating from the costocervical trunk: surgical excision for
      recurrence after successful proximal coil embolization.
AB  - A rare, true aneurysm of a branch of the right subclavian artery is described.
      Transcatheter coil embolization of the feeder artery was successful in
      obliterating blood flow into the aneurysm and the mass reduced in size. However,
      the aneurysm reenlarged over the next week of follow-up due to development and
      enlargement of the collateral vascular network. Extirpation of the aneurysm was
      performed. Histopathological examination revealed a true aneurysm.

PMID- 11833848
TI  - Failure of primary breast cancer neoangiogenesis to predict pattern of distant
      metastasis.
AB  - In the present study, the primary tumor neoangiogenesis characteristics of 81
      stage IV previously untreated breast cancers with synchronous metastasis to
      different distant sites (10 patients with soft tissue metastases, 31 with bone
      metastases, and 40 with visceral metastases) were analyzed. The primary
      intratumor microvessel density was assessed by immunohistochemical assay on
      paraffin-embedded primary tumor samples, using a monoclonal anti-CD34 antibody.
      The mean primary intratumor microvessel density (at 400x fields) was 78 +/- 39
      (SD) microvessels per field. The microvessel density was not significantly
      related to the main clinical/pathological features of the tumor (age,
      cytohistological grade, DNA ploidy, diameter, and receptor status). The
      percentage of tumor cases with high primary intratumor microvessel density (cut
      off median value of the series 73 +/- 39 microvessels/field) did not
      significantly differ in patients with bone, soft tissue, or visceral metastatic
      disease. Analysis of clinical outcome showed a significantly shorter time to
      progression and overall survival for patients with visceral metastases (P<0.001
      and P<0.0002 by log-rank, respectively). Presence of visceral metastases was
      confirmed to be the only independent prognostic factor related to a worse TTP
      (hazard risk 2.15, 95% confidence interval 1.14-4.03, P<0.02) and overall
      survival (hazard risk 1.81, 95% confidence interval 0.98-3.35, P<0.06) by
      multivariate analysis. In conclusion, the assessment of neoangiogenesis of
      primary breast cancer by CD34 expression does not provide information predictive
      of different distant sites of metastasis.

PMID- 11833849
TI  - Effect of anticonvulsant drugs on interleukins-1, -2 and -6 and monocyte
      chemoattractant protein-1.
AB  - In order to evaluate whether treatment with valproic acid or carbamazepine can
      modify interleukins and monocyte chemoattractant protein-1, we studied 40
      epileptic children and adolescents. We evaluated the patients before and after 1
      year of therapy. At the end of follow-up, the patients showed a significant
      increase of the production of interleukin-1alpha, interleukin-1beta, interleukin
      6, and monocyte chemoattractant protein-1; interleukin-2 production was
      significantly higher only in patients receiving carbamazepine. In conclusion,
      antiepileptic drugs can influence the immune system by modifying interleukin and
      chemokine concentrations; these changes seem to be independent of the serum
      concentrations of these drugs.

PMID- 11833850
TI  - Nitric oxide production by Leishmania-infected macrophages and modulation by
      prostaglandin E2.
AB  - Nitric oxide (NO), produced by the nitric oxide synthase (iNOS) enzyme, is the
      most-important molecule responsible for the killing of Leishmania parasites by
      macrophages. In previous work we have demonstrated that, after activation with
      recombinant human interferon-gamma and/or bacterial lipopolysaccharide, human
      macrophages infected with Leishmania infantum are able to produce nitric oxide
      and to express nitric oxide synthase. The arachidonate derivative prostaglandin
      E2 has been shown to modulate various macrophage activities, and in particular
      nitric oxide production, sometimes with opposite effects, related to experimental
      conditions. In this work we have evaluated nitric oxide release and parasite
      killing by peripheral blood-derived L. infantum-infected human macrophages in
      vitro stimulated with lipopolysaccharide and simultaneously treated with
      prostaglandin E2. Experiments were also performed in the presence of the nitric
      oxide synthase inhibitor L-NGmonomethylarginine (L-NMMA) and of the
      cyclooxygenase inhibitor indomethacin. Nitric oxide release in supernatants of
      macrophage cultures was measured by the Griess reaction for nitrites. Parasite
      killing was microscopically evaluated by fluorescent dyes. Results demonstrated
      that macrophages stimulated with lipopolysaccharide and treated with
      prostaglandin E2 exhibited increased nitric oxide production and parasite
      killing, which were significantly reduced by either L-NMMA or indomethacin. In
      indomethacin-treated macrophages, nitric oxide production and leishmanicidal
      ability were partially restored by the addition of exogenous prostaglandin E2.
      Taken together, these results indicate that prostaglandin E2 may be involved in
      nitric oxide production, and possibly in the host-protective immune response
      against Leishmania. Moreover, the demonstration of a stimulatory role of
      prostaglandin E2 on nitric oxide production induced by intracellular pathogens in
      humans is interesting in the light of a possible pharmacological regulation of
      nitric oxide by modulation of prostaglandin E2 synthesis.

PMID- 11833851
TI  - Relationship between lipoprotein(a) levels, oxidative stress, and blood pressure
      levels in patients with essential hypertension.
AB  - High plasma levels of lipoprotein(a) [Lp(a)] are considered a risk factor for the
      development of coronary artery disease. In vitro experiments have shown that
      oxidized Lp(a) is able to impair the arterial endothelium-dependent dilation,
      thus suggesting a possible role of Lp(a) in the genesis of essential
      hypertension. The aim of our work was to investigate the correlation of blood
      pressure levels with plasma Lp(a) concentration, apo(a) isoform size, and
      peroxidative stress in patients with essential hypertension. The study was
      performed in 54 untreated hypertensive patients whose blood pressure was
      monitored for 24 h by ambulatory blood pressure monitoring. Lp(a) concentration
      was measured by a double monoclonal antibody-based enzyme immunoassay
      demonstrated to be insensitive to apo(a) size heterogeneity. Apo(a) isoforms were
      determined by a high-resolution SDS-agarose gel electrophoresis followed by
      immunoblotting. A significant correlation was found between Lp(a) levels and the
      night-time systolic and diastolic pressures (r=0.32, P<0.05 and r=0.30, P<0.05,
      respectively), as well as with the mean night-time fall in systolic and diastolic
      blood pressures (r=-0.28, P<0.05 and r=-0.29, P<0.05, respectively). These
      relationships were further potentiated when peroxidative stress data were taken
      into consideration (r=0.37 and r=0.40, P<0.01 for the night-time systolic and
      diastolic pressures, respectively and r=-0.34 and r=-0.38, P<0.01 for the night
      time fall in systolic and diastolic blood pressures, respectively). Apo(a)
      isoform size did not affect these relationships. Our data suggest that Lp(a) and
      peroxidative stress may be involved as cofactors in essential hypertension, with
      a mechanism that remains to be elucidated.

PMID- 11833852
TI  - Italian familial defective apolipoprotein B patients share a unique haplotype
      with other Caucasian patients.
AB  - Familial defective apolipoprotein (apo) B-100 together with familial
      hypercholesterolemia are the two common genetic conditions that cause
      hypercholesterolemia. Familial defective apolipoprotein B-100 is due to mutations
      around codon 3500 of the apo B gene. The most-characterized mutation is a G>A
      transition at nucleotide 10,708 that results in the substitution of arginine by
      glutamine at codon 3500 (Apo B Arg3500Gln). Two other mutations are caused by a
      C>T transition, one at nucleotide 10,800 (Apo B Arg3531Cys) and the other at
      nucleotide 10,707 (apo B Arg3500Trp). In the present study we describe three new
      Italian cases of familial defective apolipoprotein B-100 (Apo B Arg3500Gln), one
      from the Liguria region and two from Sicily, and the haplotype of the apo B gene
      co-segregating with the mutation. By screening two groups of probands, clinically
      diagnosed as having Familial Hypercholesterolemia (700 from mainland Italy and
      305 from Sicily), the prevalence of familial defective apolipoprotein B-100 due
      to Arg3500Gln was found to be very low (0.28% and 0.65%, respectively). The
      Arg3531Cys mutation was not detected in any proband. In the three new families
      with Arg3500Gln mutation in the present study and in one previously described in
      Italy, the mutation was associated with a unique apo B haplotype, which is
      consistent with data previously reported for Caucasian patients [XbaI-, MspI+,
      EcoRI-, presence of the 5' signal peptide insertion (Ins) allele, and the 49
      repeat allele of the 3'-VNTR].

PMID- 11833853
TI  - Variable severity of beta-thalassemia patients of eastern India: effect of alpha
      thalassemia and xmnI polymorphism.
AB  - Sixty-four thalassemia and E-beta thalassemia patients were studied for factors
      that modulate the severity of the disease; i.e., mutation of beta-globin gene,
      presence of alpha-deletion, and presence of an XmnI site at the -158 position of
      the Gy gene. Presence of alpha-deletion and/or homozygosity for the XmnI site was
      in general associated with less-severe disease. About 12% of the patients
      harbored single alpha-gene deletion, and the gene frequency of the XmnI
      polymophism in these patients is 0.48.

PMID- 11833854
TI  - Variation of plasma D-dimer following surgery: implications for prediction of
      postoperative venous thromboembolism.
AB  - The prognosis of venous thromboembolism is considerably influenced by an accurate
      and fast diagnosis. Although the role of D-dimer testing in the diagnosis of
      suspected venous thromboembolism is well established for outpatients, there is
      controversial evidence on the clinical usefulness of its measurement in surgical
      patients. In order to recognize patterns of variation of D-dimer following
      surgery and identify potential pitfalls in prediction of venous thromboembolic
      complications, plasma D-dimer was assayed in 30 patients undergoing major
      elective hip surgery and 20 patients undergoing laparoscopic cholecystectomy for
      acute cholecystitis. The postoperative variation of plasma D-dimer differed
      widely between the two subgroups. Patients undergoing laparoscopic
      cholecystectomy showed D-dimer concentrations persistently increased from the
      baseline to the 15th postoperative day, whereas patients undergoing hip surgery
      were characterized by a double peak, on the 1st and 7th postoperative days. Mean
      inter-individual daily coefficient of variations of plasma D-dimer throughout the
      postoperative period were 49% (range 39%-61%) for laparoscopic cholecystectomy
      and 101% (range 72%-156%) for orthopedic surgery. The markedly heterogeneous
      fluctuation of plasma D-dimer suggests that the postoperative activation of the
      hemostatic system depends on the type and time since surgery, thus limiting the
      clinical usefulness of D-dimer testing in the diagnostic approach to
      postoperative venous thromboembolism.

PMID- 11833855
TI  - Phylogenetic significance of mole rat sleep.

PMID- 11833856
TI  - Sleep deprivation in the rat: an update of the 1989 paper.

PMID- 11833857
TI  - Sleep deprivation in the rat: X. Integration and discussion of the findings.
      1989.
AB  - The results of a series of studies on total and selective sleep deprivation in
      the rat are integrated and discussed. These studies showed that total sleep
      deprivation, paradoxical sleep deprivation, and disruption and/or deprivation of
      non-rapid eye movement (NREM) sleep produced a reliable syndrome that included
      death, debilitated appearance, skin lesions, increased food intake, weight loss,
      increased energy expenditure, decreased body temperature during the late stages
      of deprivation, increased plasma norepinephrine, and decreased plasma thyroxine.
      The significance of this syndrome for the function of sleep is not entirely
      clear, but several changes suggested that sleep may be necessary for effective
      thermoregulation.

PMID- 11833858
TI  - Clinical aspects of narcolepsy-cataplexy across ethnic groups.
AB  - STUDY OBJECTIVES: The objectives of this study were to compare severity and
      clinical presentation for narcolepsy-cataplexy across various ethnic groups. A
      large sample of narcoleptic patients was also used to further describe
      symptomatology and natural history for this sleep disorder. DESIGN: Retrospective
      review of clinical data ascertained from the Stanford Sleep Inventory,
      polysomnography and MSLT data, as well as clinical notes. Ethnicity was narrowly
      defined as African (Black) Americans, Caucasians, Asians, and Latinos when both
      parents and the subject identified with a given ethnic group. SETTING: N/A.
      PARTICIPANTS: We compared the severity and clinical presentation of narcolepsy in
      64 African Americans, 353 Caucasians, 32 Asians, 26 Latinos, and 9 subjects of
      mixed ethnicity. Subjects were recruited through the Stanford center for
      narcolepsy research. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: A striking
      similarity in symptomatology, age of onset, and disease severity was found across
      ethnic groups. Mean age of onset for sleepiness, hypnagogic hallucinations, sleep
      paralysis and cataplexy were 19.20, 19.50, 20.11 and 23.02 years old. We also
      found that narcoleptic patients have slightly but significantly elevated body
      mass index relative to normative data (106.6% of matched controls, p<0.005) and
      are born slightly more frequently during the month of March. A tight correlation
      between our previously validated cataplexy scale and DQB1*0602 positivity was
      observed. Two thirds of patients reported having cataplexy with laughing, 92% of
      those being DQB1*0602 positive independent of ethnicity. CONCLUSIONS: These
      results confirm the similarities in clinical presentation and natural history of
      narcolepsy-cataplexy in a large number of patients of various ethnic groups and
      cultural backgrounds.

PMID- 11833859
TI  - Diagnoses received by narcolepsy patients in the year prior to diagnosis by a
      sleep specialist.
AB  - STUDY OBJECTIVES: Narcolepsy is a neurological disorder whose clinical features
      include excessive daytime sleepiness, hypnagogic hallucinations, cataplexy, sleep
      paralysis, and disrupted nocturnal sleep. It has been shown that there may be
      quite a long interval between the onset of symptoms, and the correct diagnosis.
      We tested the hypothesis that given their severe symptomatology, these patients
      would have been diagnosed more often with a variety of psychiatric and neurologic
      conditions than controls in the year prior to confirmation of their narcolepsy
      diagnosis. DESIGN: Using the Province of Manitoba Health database, we compared
      the diagnoses made in the year prior to initial sleep disorder center evaluation
      of 77 patients with narcolepsy (33 males, 44 females) and 1,155 matched control
      subjects from the general population. SETTING: Sleep disorders center in
      University-based teaching hospital PARTICIPANTS: N/A. INTERVENTIONS: N/A.
      MEASUREMENTS AND RESULTS: Patients were much more likely than controls to be
      diagnosed with mental disorders (Odds ratio (OR) = 4.0645; 95% confidence limit
      (CL) = 2.4671-6.6962; p<0.0001) and nervous system disorders (OR= 5.0495; CL =
      3.0606 -8.3309; p<0.0001) and there was a trend towards more injuries in these
      patients (OR =1.6316; CL = 0.9857-2.7007; p=0.0514). We found that cases were
      statistically much more likely than controls to have received a diagnosis for
      neurotic disorders (17% of cases), depression (16%), personality disorders (3%)
      and adjustment reaction (4%). Although the cases had twice as many doctor visits
      as the controls (9.3 +/- 0.97 (sem) vs. 4.8 +/- 0.17 p<0.0001), only 38% of them
      had received a diagnosis of narcolepsy in the year prior to sleep specialist
      evaluation. Neurologists had the highest "success rate" for correct diagnosis:
      neurologists diagnosed narcolepsy in 55% of the cases they had seen. The other
      medical practitioners diagnosed narcolepsy in a much smaller percentage of the
      cases they had seen: 23.5% for internists (excluding neurologists), 21.9% for
      general practitioners, 11.1% for psychiatrists, and 0% for pediatricians.
      CONCLUSIONS: In the year prior to documentation of narcolepsy in a sleep
      disorders center, patients with narcolepsy were diagnosed with a wide variety of
      mental and neurologic disorders. Our findings are supportive of either the
      coexistence of these disorders in narcolepsy patients or a high frequency of
      missed diagnosis by their clinicians. The latter may help explain the very long
      interval between onset of symptoms and correct diagnosis.

PMID- 11833860
TI  - A randomized, double blind, placebo-controlled multicenter trial comparing the
      effects of three doses of orally administered sodium oxybate with placebo for the
      treatment of narcolepsy.
AB  - STUDY OBJECTIVES: To evaluate and compare the efficacy and safety of three doses
      of sodium oxybate and placebo for the treatment of narcolepsy symptoms. DESIGN: A
      multicenter, double blind, placebo-controlled trial. SETTING: N/A. PARTICIPANTS:
      Study subjects were 136 narcolepsy patients with 3 to 249 (median 21) cataplexy
      attacks weekly. INTERVENTIONS: Prior to baseline measures, subjects discontinued
      anticataplectic medications. Stable doses of stimulants were permitted. Subjects
      were randomized in blinded fashion to receive 3, 6, or 9 g doses of sodium
      oxybate or placebo taken in equally divided doses upon retiring to bed and 2.5-4
      hours later for 4 weeks. MEASUREMENTS AND RESULTS: Disease symptoms and adverse
      events were recorded in daily diaries. The primary measure of efficacy was the
      change from baseline in weekly cataplexy attacks. Secondary measures included
      daytime sleepiness using the Epworth Sleepiness Scale (ESS), inadvertent daytime
      naps/sleep attacks and nighttime awakenings. Investigators assessed changes in
      disease severity using Clinical Global Impression of Change (CGI-c). Compared to
      placebo, weekly cataplexy attacks were decreased by sodium oxybate at the 6 g
      dose (p=0.0529) and significantly at the 9 g dose (p=0.0008). The ESS was reduced
      at all doses, becoming significant at the 9 g dose (p=0.0001). The CGI-c
      demonstrated a dose-related improvement, significant at the 9 g dose (p=0.0002).
      The frequency of inadvertent naps/sleep attacks and the nighttime awakenings
      showed similar dose-response trends, becoming significant at the 9 g dose
      (p=0.0122 and p=0.0035, respectively). Sodium oxybate was generally well
      tolerated at all three doses. Nausea, headache, dizziness and enuresis were the
      most commonly reported adverse events. CONCLUSIONS: Sodium oxybate significantly
      improved symptoms in patients with narcolepsy and was well tolerated.

PMID- 11833861
TI  - Severity of narcolepsy among French of different ethnic origins (south of France
      and Martinique).
AB  - STUDY OBJECTIVES: The aim of the study was to describe the clinical and
      polygraphical characteristics of narcoleptics, with and without cataplexy and to
      assess HLA predisposition across two different ethnic populations. DESIGN AND
      SETTING: Patients were 126 men and 58 women referred to the Montpellier Sleep
      Disorders Center (Mtp) and 12 men and 8 women referred to the Fort-de-France
      Sleep Disorders Center (FdF) (Martinique, a French West Indy island) with
      symptoms of narcolepsy. PARTICIPANTS: Narcoleptics were included if they had both
      excessive daytime sleepiness and clear-cut cataplexy (for the group with
      cataplexy), a mean sleep latency of less than 8 minutes and at least two sleep
      onset REM periods. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Narcolepsy
      without clear-cut cataplexy was rare (12/172) in the Mtp population whereas it
      was as frequent as full-blown narcolepsy (10/10) in the FdF population.
      Comparison between narcoleptics with cataplexy from the Mtp and FdF populations
      revealed a younger age of onset, a trend towards more severe sleepiness and lower
      frequency of cataplexy in Martinicans. Comparison between narcoleptics without
      cataplexy from the Mtp and FdF population revealed a higher frequency of
      hypnagogic hallucinations and sleep paralysis and a trend towards more severe
      sleepiness in Martinicans. 4.2% of the Mtp and 15% of the FdF patients were
      negative for HLA DR2. However all of them were positive for HLA DQ1. Moreover, a
      tight association with HLA DRB1*1503 was observed in Martinicans in contrast with
      DRB1*1501 in the Mtp population. Association with HLA DQB1*0602 was observed in
      99.4% of narcoleptics with cataplexy and in 89.5% of those without cataplexy.
      CONCLUSIONS: Narcolepsy is a heterogeneous clinical syndrome, the more so as
      ethnic origins are considered. A modulating effect of HLA and non-HLA genes on
      symptoms disease may explain these differences.

PMID- 11833862
TI  - Circulating vascular endothelial growth factor levels in patients with
      obstructive sleep apnea.
AB  - STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is associated with intermittent
      hypoxia during sleep. Vascular endothelial growth factor (VEGF) has detectable
      levels in the circulation and its expression is highly regulated by oxygen
      tension. We therefore hypothesized that serum VEGF levels will be elevated in
      patients with OSA. DESIGN: Blood samples were collected at random times during
      the day from 68 adults and 41 children who were clinically suspected for the
      presence of OSA, and who underwent overnight polysomnography. SETTING: University
      hospital sleep laboratory. PARTICIPANTS: N/A. INTERVENTIONS: N/A. MEASUREMENTS
      AND RESULTS: For both children and adults, serum VEGF levels were significantly
      higher in polysomnographically confirmed OSA (AHI>15 and AI>5 in adults and
      children respectively) when compared to those with mild or no disease (p<0.0001).
      Furthermore, significant correlations were found between VEGF concentrations and
      respiratory disturbance index and sleep time spent at SpO2 <90%. In addition,
      VEGF levels in children were higher for any given duration of hypoxia during
      sleep (p<0.0001). No differences in VEGF emerged between evening and morning
      samples. However, temporal delays in blood sample processing were associated with
      spuriously increased VEGF concentrations. Exploratory analysis of the data
      revealed that serum VEGF concentrations of >150 pg/ml in adults and >100 pg/ml in
      children were predictive of OSA, when an apnea-hypopnea index >30 and an apnea
      index >5 were used as disease criteria in adults and children, respectively.
      CONCLUSIONS: We conclude that circulating VEGF levels are frequently elevated in
      OSA patients, and may play a role in the regulation of tissue oxygen delivery.

PMID- 11833863
TI  - Body position and obstructive sleep apnea in children.
AB  - STUDY OBJECTIVES: In adults, sleep apnea is worse when the patient is in the
      supine position. However, the relationship between sleep position and obstructive
      apnea in children is unknown. The objective of this study was to evaluate the
      relationship between obstructive apnea and body position during sleep in
      children. DESIGN: Retrospective analysis of the relationship between body
      position and obstructive apnea in obese and non-obese children. SETTING: Tertiary
      care pediatric sleep center. PATIENTS: Otherwise healthy children, aged 1-10
      years, undergoing polysomnography for suspected obstructive sleep apnea syndrome.
      Obese and non-obese children were evaluated separately. INTERVENTIONS:
      Retrospective review of the relationship between sleep position and obstructive
      apnea during polysomnography. MEASUREMENTS AND RESULTS: Eighty polysomnograms
      from 56 non-obese and 24 obese children were analyzed. Body position was
      determined by a sensor during polysomnography, and confirmed by review of
      videotapes. Children had a lower obstructive apnea hypopnea index when supine vs.
      prone, and shorter apneas when supine then when on their side. There was no
      difference in apnea duration between the supine and prone positions. Obese and
      non-obese children showed similar positional changes. CONCLUSIONS: Children with
      obstructive sleep apnea, in contrast to adults, breathe best when in the supine
      position.

PMID- 11833864
TI  - Larger phase angle between sleep propensity and melatonin rhythms in sighted
      humans with non-24-hour sleep-wake syndrome.
AB  - STUDY OBJECTIVES: This study was aimed to clarify phase angle between sleep
      propensity and the circadian pacemaker in patients with non-24-hour sleep-wake
      syndrome (Non-24). DESIGN AND SETTING: A case-control study was underaken.
      PARTICIPANTS: Sighted patient with Non-24 (4 males and 1 female, aged 16 to 39
      y), and sex- and age-matched healthy controls (12 males and 3 females, aged 19 to
      35 y) participated the study. MEASUREMENT AND INTERVENTION: Following an
      actigraphic assessment of the sleep-wake cycle in their homes, the participants
      entered an ultra-short sleep-wake schedule together with simultaneous measurement
      of dim light melatonin rhythm after 24-hour sleep deprivation. RESULTS: The
      period of the sleep-wake cycle observed at home was longer in the Non-24 patients
      (25.12 hours) than in the controls (24.02 hours, p<0.0001). The interval from
      sleep propensity (SP) onset to the melatonin midpoint (MLmid) was significantly
      shorter in the Non-24 patients than in the controls. The interval from the MLmid
      to the SP offset was significantly longer in the Non-24 patients than in the
      controls. CONCLUSIONS: It was postulated that Non-24 sufferers' delayed SP onset
      relative to the circadian pacemaker may accelerate the light-induced phase-delay,
      leading to sleep-wake cycle that is longer than 24 hours.

PMID- 11833865
TI  - Factors related to the occurrence of isolated sleep paralysis elicited during a
      multi-phasic sleep-wake schedule.
AB  - STUDY OBJECTIVES: To further investigate mechanisms of isolated sleep paralysis
      (ISP) in normal individuals, we experimentally elicited ISPs by facilitating
      sleep onset REM periods (SOREMP), a prerequisite of ISPs, and examined behavioral
      and psychological measurements relating to ISP appearances. DESIGN: The multi
      phasic sleep/wake schedule (MPS) began at approximately midnight and ended when
      net sleep reached 7.5 hours. Participants were awakened after every 5 min of REM
      sleep to obtain a maximum number of SOREMPs. Upon each awakening, mentation
      reports and subjective measurements were collected. Performance tests were then
      assigned. SETTING: Sleep lab, Tokyo Metropolitan Institute for Neurosciences,
      Japan. PARTICIPANTS: Thirteen healthy Japanese students (10 males) with high self
      reported frequencies of ISPs but no other narcolepsy-related symptoms.
      INTERVENTIONS:  MEASUREMENTS AND RESULTS: From 184 sleep interruptions, 8 ISP
      episodes were obtained. In within participant comparisons between episodes with
      and without ISPs, the vigilance task (VT) reaction times were elevated before
      SOREMPs with ISPs. In between analyses (ISP vs non-ISP), the ISP group showed
      poorer performance, more complaints of physical, mental, and neurotic symptoms,
      increased subjective fatigue and increased stage 1 throughout the entire
      schedule. VT hit rates remained constant in the non-ISP group, but dropped in the
      later part of schedule in the ISP group. Subjective sleepiness dropped over time
      in the non-ISP group while it slightly increased in the ISP group. CONCLUSIONS:
      ISP is likely to appear as a phenotype of REM dissociation during SOREMP when
      participants with low tolerance for disrupted sleep-wake rhythms are placed in
      this type of schedule.

PMID- 11833866
TI  - Role of uterine artery Doppler flow in fibroid embolization.
AB  - OBJECTIVE: To determine whether Doppler flow measurements are useful in
      predicting variables associated with uterine fibroid embolization, including
      shrinkage of the uterus and myomas, adenomyosis, and uterine fibroid embolization
      failure. METHODS: A group of 227 patients with menorrhagia or postmenopausal
      bleeding secondary to uterine myomas were evaluated with uterine artery Doppler
      flow sonography before uterine fibroid embolization. Doppler flow measurements
      were repeated 6 months after uterine fibroid embolization for 188 of the
      patients. Data were analyzed for correlations between peak systolic velocity and
      uterine fibroid embolization patient data, including size and shrinkage of the
      uterus and myomas, embolization particle size, adenomyosis, and uterine fibroid
      embolization failure. RESULTS: Initial peak systolic velocity was positively
      correlated with the size and shrinkage of myomas and uterine volume. Peak
      systolic velocity was positively correlated with the size and load of
      embolization particles and was significantly lower (mean, 33.2 cm/s) in patients
      with adenomyosis than those without adenomyosis (mean, 39.3 cm/s). High peak
      systolic velocity (>64 cm/s) was a significant predictor of failure.
      Postembolization peak systolic velocity (mean, 21.85 cm/s) was significantly
      lower than preembolization peak systolic velocity (mean, 40.33 cm/s) and was not
      correlated with uterine fibroid embolization variables. CONCLUSIONS: Doppler flow
      measurements can aid in predicting adenomyosis and uterine fibroid embolization
      failure. Postembolization peak systolic velocity did not show value.

PMID- 11833867
TI  - Predicting atypia inside endometrial polyps.
AB  - OBJECTIVE: To evaluate the efficacy of color Doppler exploration for assessing
      atypia inside endometrial polyps. METHODS: A prospective study was conducted in a
      tertiary university hospital. Eight hundred six patients with endometrial polyps
      were studied with color Doppler sonography, and the resistive index inside the
      polyp stalk was obtained. The patients were then referred for hysteroscopic
      resection, and pathologic analysis was performed. RESULTS: Thirty-five polyps
      with sonographic indications of atypia were pathologically confirmed. Sonographic
      indications of atypia inside 16 polyps were not confirmed. Three nonquestionable
      endometrial polyps had atypia inside them. CONCLUSIONS: Low Doppler resistance is
      highly predictive of atypia inside endometrial polyps.

PMID- 11833868
TI  - Three-dimensional color Doppler sonography and uterine artery arteriography of
      fibroids: assessment of changes in vascularity before and after embolization.
AB  - OBJECTIVE: To assess the accuracy of three-dimensional color Doppler sonography
      and uterine artery arteriography in depicting changes in fibroid vascularity
      before and after embolization. METHODS: Preembolization and postembolization
      three-dimensional color Doppler sonography and selective uterine artery
      arteriography were retrospectively compared in 15 patients who underwent uterine
      artery embolization for treatment of symptomatic fibroids. Three-dimensional
      color Doppler sonography was performed by using a scanner with color power
      angiographic imaging capability. Vascularity was quantified by using an
      estimation of power-weighted pixel density as described by our group in
      previously published studies. Uterine artery arteriography was performed by using
      a standard selective microcatheter embolization technique. For purposes of
      comparison, fibroids were classified as either hypervascular or hypovascular
      relative to myometrial vascularity before and minutes to several hours after
      uterine artery embolization. Changes in fibroid vascularity (i.e., from
      hypervascular to hypovascular) as depicted by three-dimensional color Doppler
      sonography were compared with those shown on uterine artery arteriography and
      classified as being in agreement or disagreement. RESULTS: In 13 (87%) of 15
      patients there was agreement; in 2 (13%) of 15 there was disagreement. In both
      cases of disagreement, three-dimensional color Doppler sonography showed
      collateral flow not depicted by uterine artery arteriography The mean reduction
      in quantitated vascularity after uterine artery embolization was 44% (range, 19%
      78%). CONCLUSIONS: Three-dimensional color Doppler sonography accurately depicts
      fibroid vascularity and in some cases can reveal collateral flow not depicted by
      uterine artery arteriography.

PMID- 11833869
TI  - Impact of added biopsy areas on prostate cancer detection: preliminary analysis.
AB  - OBJECTIVE: To evaluate variations in prostate cancer detection relevant to the
      number and areas of biopsy cores. METHODS: Ninety patients with elevated prostate
      specific antigen levels, abnormal physical examination findings, or both had
      ultrasound examinations plus biopsies. Forty-nine patients had 11 biopsies, and
      41 patients had 6 biopsies. The numbers of cancers detected were compared on a
      patient-by-patient basis and by all biopsy sites grouped together. An analysis of
      the relationship between a positive gray scale sonographic finding and the
      presence of adenocarcinoma was done. RESULTS: On a patient-by-patient basis, 43%
      of patients who had 11 biopsies had adenocarcinoma. In patients who had 6
      biopsies, 32% had adenocarcinoma. Thirty-eight percent of the additional cancers
      found in the 11-biopsy group were in 5 additional areas not sampled in the 6
      biopsy group. Of the total of 539 biopsy specimens obtained in the 11-biopsy
      group, 56 (10%) had adenocarcinoma; 43% of these 56 were positive in the 5
      additional areas not sampled in the 6-biopsy group. No statistical differences (P
      > .05) were found for mean age, mean prostate-specific antigen level, and mean
      volume in the groups with 11 and 6 biopsies. This indicated that the observed
      difference was not related to any of these factors. Similar pathologic data were
      found for patients with prostatic intraepithelial neoplasia. CONCLUSIONS: Our
      data indicate the added value of additional biopsy sites over the usual 6
      biopsies to increase the yield of adenocarcinoma and prostatic intraepithelial
      neoplasia detected. The added biopsy sites of the central and midperipheral
      glands were areas where additional specimens positive for adenocarcinoma and
      prostatic intraepithelial neoplasia were obtained.

PMID- 11833870
TI  - Enhancement of hepatic hemangiomas with levovist on coded harmonic angiographic
      ultrasonography.
AB  - OBJECTIVE: To evaluate the pattern of contrast enhancement with Levovist on coded
      harmonic angiographic ultrasonography of hepatic hemangiomas. METHODS: Twenty
      hemangiomas were evaluated with coded harmonic angiographic ultrasonography and a
      microbubble contrast agent. Verification of the diagnosis of a hemangioma was
      made by means of dynamic computed tomography (n = 8), dynamic magnetic resonance
      imaging (n = 1), radionuclide scanning (n = 6), or follow-up ultrasonography (n =
      5). Ultrasonographic images were obtained before contrast agent administration
      and with a bolus injection of 2.5 g of a microbubble contrast agent (300 mg/mL
      Levovist; Schering AG, Berlin, Germany) every 10 to 15 seconds for 5 minutes. The
      contrast enhancement patterns of the 20 hemangiomas were assessed. RESULTS: The
      tumor diameters as measured on ultrasonography were 7 to 97 mm (mean, 26.7 mm).
      Of the 20 hemangiomas, peripheral globular enhancement with progressive
      centripetal fill-in was shown in 15 (75%), rimlike enhancement with progressive
      centripetal fill-in was shown in 2 (10%), and homogeneous enhancement was shown
      in 1 (5%). In the remaining 2 lesions (10%), the enhancement patterns could not
      be seen, because they were not found on coded harmonic angiographic
      ultrasonography. CONCLUSIONS: Coded harmonic angiographic ultrasonography with a
      microbubble contrast agent can depict the typical enhancement pattern in most
      hepatic hemangiomas.

PMID- 11833871
TI  - Contrast-enhanced power Doppler sonography of the intestinal wall in the
      differentiation of hypervascularized and hypovascularized intestinal obstructions
      in patients with Crohn's disease.
AB  - OBJECTIVE: To use power Doppler sonography to quantify the vascularization in the
      area of stenosed bowel segments in patients with Crohn's disease and to draw
      conclusions from these findings with regard to the development of these stenoses.
      METHODS: The study collective included 11 patients with confirmed Crohn's disease
      and sonographically visualized stenoses of the small bowel together with
      intermittent abdominal cramping as a clinical correlate. Power mode examination
      was repeated after application of a sonographic signal-enhancing agent.
      Semiquantitative evaluation based on the sonographically indicated degree of
      vascularization led to the presumptive diagnosis of either inflammatory or
      cicatricial intestinal obstruction. Sonographic diagnoses were compared with the
      findings of surgery and subsequent histologic examination or with patients'
      clinical responses to conservative therapy. RESULTS: Nine of 11 patients
      underwent surgery within 1 year of examination. All 3 cases in which sonography
      had facilitated the diagnosis of cicatricial stenosis were confirmed at
      postoperative histologic examination; similarly, the surgical and histologic
      findings in the other 6 patients confirmed the sonographic diagnosis of
      inflammatory stenosis. CONCLUSIONS: Power Doppler sonography in combination with
      the use of a signal-enhancing agent appears to be effective in the recognition of
      predominantly cicatricial stenoses in patients with Crohn's disease.

PMID- 11833872
TI  - Contrast-enhanced two- and three-dimensional sonography for evaluation of intra
      abdominal hemorrhage.
AB  - OBJECTIVE: To determine whether a contrast agent enhances sonographic detection
      of bleeding sites in the abdomen and whether contrast-enhanced three-dimensional
      sonography provides additional information compared with contrast-enhanced two
      dimensional sonography. METHODS: Bleeding sites were created within the livers (n
      = 3), spleens (n = 5), and kidneys (n = 3) of 3 dogs. A sonographic contrast
      agent with vascular and parenchymal enhancement capabilities was administered
      intravenously at a dose of 0.02 mL/kg. Before and after each contrast agent
      injection, the bleeding sites were imaged with two- and three-dimensional
      sonography in gray scale harmonic imaging and color flow modes. Sonographic
      findings were compared with gross pathologic findings. RESULTS: Noncontrast
      enhanced sonography was not able to show the specific location of the active
      bleeding in any of the organs evaluated. The contrast agent enhanced the
      sonographic detection of blood flow in normal vessels and extravasated blood from
      damaged vessels or organs in all cases. Intrasplenic and intrahepatic hematomas
      were better identified on delayed imaging sequences because there was marked
      enhancement of the normal parenchyma, whereas the hematomas remained unenhanced.
      Reconstructed three-dimensional sonography showed spatial relationships of the
      bleeding sites and surrounding structures. Gross pathologic findings were
      consistent with the contrast-enhanced sonographic results. CONCLUSIONS: Contrast
      enhanced sonography improves the detection and evaluation of abdominal bleeding
      sites. Contrast-enhanced three-dimensional sonography appears to provide
      additional information when compared with two-dimensional sonography.

PMID- 11833873
TI  - Ultrasonography of the scrotum: technique, anatomy, and pathologic entities.
AB  - OBJECTIVE: To review the ultrasonographic technique, anatomy, and pathologic
      entities found in the scrotum during evaluation of scrotal masses, acute scrotal
      pain, and male infertility. METHOD: A pictorial review of cases with diagrams of
      pertinent anatomic features and findings is presented. RESULTS: Ultrasonography
      in conjunction with color and pulsed Doppler imaging has supplanted other imaging
      modalities in the evaluation of scrotal diseases and disorders. Ultrasonography
      is valuable in the evaluation of the acutely painful scrotum in addition to
      scrotal masses and male infertility. Advances in ultrasonographic spatial and low
      contrast resolution have improved our ability to more clearly define diagnoses
      for the referring urologist and have led to new observations that are currently
      being investigated and have yet to be fully understood. Microlithiasis and the
      mottled appearance of seminiferous tubule sclerosis and atrophy are 2 such
      entities. This article reviews the pertinent normal scrotal anatomy and the use
      of ultrasonography in the evaluation and classification of acute scrotal pain,
      scrotal masses, male infertility, and trauma. This review article also discusses
      pitfalls of color Doppler imaging in assessment of the scrotum and how to avoid
      them. CONCLUSION: The use of ultrasonography in the evaluation of the scrotum
      benefits from an understanding of scrotal anatomy and familiarity with potential
      pitfalls of color Doppler and pulsed Doppler evaluation.

PMID- 11833874
TI  - Nontumorous vascular malformations in the liver: color Doppler ultrasonographic
      findings.
AB  - OBJECTIVE: To investigate color Doppler and spectral wave characteristics of
      nontumorous vascular malformations in the liver. METHODS: From September 1995 to
      January 2001, 32 cases of vascular malformations were identified by means of
      color Doppler ultrasonography and spectral wave analysis. Computed tomography,
      angiography, or both were performed in all cases. RESULTS: Five arterioportal and
      14 portovenous malformations, 1 arteriovenous malformation, and 4 portoportal and
      8 venovenous shunts were detected. Associations with Rendu-Osler-Weber syndrome
      in 6 cases and with cirrhotic liver in 12 cases were found Fourteen patients were
      liver disease free. In 3 cases, interventional procedures were necessary to
      reduce portal hypertension or cardiac dysfunction. The incidence of finding
      vascular malformations in 12,000 patients was 0.1%. CONCLUSIONS: Nontumorous
      vascular malformations are rare disorders in the liver. They may appear in
      patients with healthy livers and in patients with portal hypertension. Color
      Doppler ultrasonography and spectral wave analysis are capable of showing and
      differentiating different types of hepatic vascular malformations.

PMID- 11833875
TI  - Maxillofacial cysticercosis: uncommon appearance of a common disease.
AB  - OBJECTIVE: To highlight the sonographic appearances of cysticercosis involving
      uncommon muscular sites. METHODS: Two patients with nodular swelling involving
      the tongue and maxillary region were examined with high-resolution sonography.
      RESULTS: Sonographic examination revealed an anechoic area with a small calcified
      scolex suggesting cysticercus infection. CONCLUSIONS: High-resolution sonography
      is a noninvasive and nonionizing imaging modality that plays an important role in
      establishing the diagnosis of cysticercosis.

PMID- 11833876
TI  - Renal lymphangioma manifested as a solid mass on ultrasonography and computed
      tomography.

PMID- 11833877
TI  - Ultrasonographic diagnosis of pelvic echinococcosis: case report and review of
      the literature.

PMID- 11833878
TI  - Various appearances of multiple angiomyolipomas in the same kidney in a patient
      without tuberous sclerosis.

PMID- 11833879
TI  - Constrictive penile band injury: color Doppler sonographic assessment.

PMID- 11833880
TI  - Right ovarian vein aneurysm.

PMID- 11833881
TI  - Time allocation and reimbursement for routine obstetric ultrasonography.

PMID- 11833882
TI  - Optimization of broadband uniform beam profile interdigital transducers weighted
      by assignment of electrode polarities.
AB  - This paper considers techniques for optimizing surface acoustic wave (SAW)
      interdigital transducers (IDTs) with uniform electrode length (no apodization).
      Unlike other optimization techniques developed for this type of IDT, the
      algorithms proposed here choose the best electrode structure on the basis of how
      well it meets the specifications, not in the time domain, but in the frequency
      domain directly. In the first step of the optimization, a periodic transducer is
      synthesized. The weighting technique for providing a desired frequency response
      involves assigning polarities to the individual electrodes. The next step of the
      IDT selectivity improvement is the optimization of the electrode positions. In
      addition, the second algorithm can synthesize specified nonsymmetric frequency
      responses. A set of IDTs and SAW filters with bandwidths of 1 to 14% has been
      designed using this algorithm.

PMID- 11833883
TI  - Interpreting anomalously low voltage noise in two-channel measurement systems.
AB  - In this work we 1) analyze and give a theoretical explanation for the anomalously
      low cross-spectral density of voltage fluctuations that is observed when two
      thermal noise sources with matched intensities are coupled to the inputs of two
      channel phase modulation (PM) or amplitude modulation (AM) noise measurement
      systems (NMS), 2) empirically evaluate spectral resolutions of different types of
      measurement systems, and 3) discuss noise measurement techniques involving cross
      correlation signal processing. Our work shows that the statistical uncertainty,
      which sets the ultimate spectral resolution in the thermal noise limited regime,
      is approximately the same for both systems. However, in practical terms, the non
      stationary nature of the noise, the temporal separation of calibration and
      measurement, and the difficulty of reproducing the calibrations for two
      measurements make it extremely difficult to resolve noise that is more than 10 dB
      below the noise floor in a single channel NMS. In a two-channel NMS, however, the
      calibrations of the two channels are carried out simultaneously, and one can take
      full advantage of a large number of averages and make reproducible noise
      measurements with resolution 10 dB below the noise floor of a single channel NMS.

PMID- 11833885
TI  - Accurate measurements of the acoustical physical constants of synthetic alpha
      quartz for SAW devices.
AB  - Accurate measurements of the acoustical physical constants (elastic constants,
      piezoelectric constants, dielectric constants, and density) of commercially
      available and widely used surface acoustic wave (SAW)-grade synthetic a-quartz
      are reported. The propagation directions and modes of bulk waves optimal for
      accurately determining the constants were selected through numerical
      calculations, and three principal X-, Y-, and Z-cut specimens and several rotated
      Y-cut specimens were prepared from a single crystal ingot to determine the
      constants and to confirm their accuracy. All of the constants were determined
      through highly accurate measurements of the longitudinal velocities, shear
      velocities, dielectric constants, and density. The velocity values measured for
      the specimens that were not used to determine the constants agreed well with
      those calculated from the determined constants, within a difference of +/- 0.20
      m/s (+/- 0.004%).

PMID- 11833886
TI  - Evaluation of a novel surface acoustic wave gyroscope.
AB  - A novel type of gyroscope sensor using metal dot arrays on the surface of a
      surface acoustic wave (SAW) device has recently been independently proposed. In
      this paper, we report experimental trials of several devices fabricated to
      evaluate the effects described and also an order-of-magnitude estimate of the
      sensitivity to be expected. The conclusions are that this device is extremely
      insensitive as currently proposed.

PMID- 11833884
TI  - Real-time rectilinear volumetric imaging.
AB  - Current real-time volumetric scanners use a 2-D array to scan a pyramidal volume
      consisting of many sector scans stacked in the elevation direction. This scan
      format is primarily useful for cardiac imaging to avoid interference from the
      ribs. However, a real-time rectilinear volumetric scan with a wider field of view
      close to the transducer could prove more useful for abdominal, breast, or
      vascular imaging. In previous work, computer simulations of very sparse array
      transducer designs in a rectilinear volumetric scanner demonstrated that a Mills
      cross array showed the best overall performance given current system constraints.
      Consequently, a 94 x 94 Mills cross array including 372 active channels operating
      at 5 MHz has been developed on a flexible circuit interconnect. In addition, the
      beam former delay software and scan converter display software of the Duke
      volumetric scanner were modified to achieve real-time rectilinear volumetric
      scanning consisting of a 30-mm x 8-mm x 60-mm scan at a rate of 47 volumes/s.
      Real-time rectilinear volumetric images were obtained of tissue-mimicking
      phantoms, showing a spatial resolution of 1 to 2 mm. Images of carotid arteries
      in normal subjects demonstrated tissue penetration to 6 cm.

PMID- 11833887
TI  - Exact analysis of dispersive SAW devices on ZnO/diamond/si-layered structures.
AB  - In this paper, a formulation for calculating the effective permittivity of a
      piezoelectric layered SAW structure is given, and the exact frequency response of
      ZnO/diamond/Si-layered SAW is calculated. The effective permittivity and phase
      velocity dispersion of a ZnO/diamond/Si-layered half space are calculated and
      discussed. The frequency response of an unapodized SAW transducer is calculated,
      and the center frequency shift caused by the velocity dispersion is explained. In
      addition, the electromechanical coupling coefficients of the ZnO/diamond/Si 
      layered half space based on two different formulas are calculated and discussed.
      Finally, based on the results of the study, we propose an exact analysis for
      modeling the layered SAW device. The advantage of using the effective
      permittivity method is that, not only the null frequency bandwidth, but also the
      center frequency shift and insertion loss can be evaluated.

PMID- 11833888
TI  - Design of ultrasonic array elements for acoustic power considerations.
AB  - In sound-transmitting applications such as therapeutic ultrasound, the acoustic
      power at a particular operating frequency is a critical figure of merit for
      transducer/array design. A design methodology for enhancing the acoustic power
      radiated from fluid-loaded piezoelectric array elements at a fixed frequency is
      developed in this paper. A gradient-based optimization algorithm is integrated
      within the finite element framework to guide the determination of the two design
      variables, the piezoelectric element thickness and the matching layer thickness,
      to optimize the acoustic power output. A method for avoiding explicit remeshing
      in the optimization iteration is presented. Optimized designs are determined
      numerically, and the effectiveness of the design method is confirmed by
      experimental measurements. The validated numerical analysis also shows that
      conventional design strategies using one-dimensional transducer analysis and rule
      of-thumb matching layer or protection layer sizing rules may not give the best
      design for array elements in acoustic power applications.

PMID- 11833889
TI  - Improvements in the ultrasonic contrast of targeted perfluorocarbon nanoparticles
      using an acoustic transmission line model.
AB  - Targeted acoustic contrast agents offer the potential for sensitive ultrasonic
      detection of pathologic tissues. We have previously reported the development of a
      ligand-targeted, lipid-encapsulated, liquid perfluorodichlorooctane ultrasonic
      contrast system with a small nominal particle size (approximately 250-nm
      diameter). Perfluorocarbon nanoparticles substantially increase reflectivity when
      bound to targeted surfaces, and we propose that this system can be approximated
      physically as a simple, thin layer, acoustic transmission line. In this study, we
      evaluate this model and compare the ultrasonic reflectivity of different
      perfluorocarbon formulations with widely varying acoustic impedances targeted to
      either nitrocellulose membranes or plasma thrombi in vitro. Five perfluorocarbons
      were investigated: perfluorohexane (PFH), perfluorooctane (PFO), perfluorooctyl
      bromide (PFOB), perfluorodichlorooctane (PFDCO), and perfluorodecalin (PFD).
      Ultrasonic reflection was measured by acoustic microscopy (17 to 35 MHz).
      Acoustic reflectivity was increased (P < 0.05) by all targeted perfluorocarbon
      formulations, and the magnitude of the contrast effect was inversely correlated
      with the perfluorocarbon acoustic impedance. PFH nanoparticles exhibited the
      greatest enhancement, and PFD nanoparticles showed the least. The acoustic
      transmission line model predicted well the relative differences in acoustic
      reflectivity and frequency dependence among the perfluorocarbon formulations. For
      future clinical applications, PFO nanoparticles may provide the best combination
      of acoustic enhancement, in vivo physical stability, and safety.

PMID- 11833890
TI  - Strain compounding: a new approach for speckle reduction.
AB  - A new compounding technique for reducing speckle brightness variations is
      proposed. This method exploits the decorrelation between signals under different
      strain states. The different strain states can be created using externally
      applied forces such as the ones used in sonoelastography. Such forces produce
      three-dimensional tissue motion. By correcting only the in-plane (i.e., axial and
      lateral) motion, the images under different strain states have similar
      characteristics except for speckle appearance caused by the uncorrected out-of
      plane (i.e., elevational) motion. Additional speckle decorrelation is also
      introduced through tissue motion correction caused by the change of effective in
      plane sample volume geometry. Therefore, these images can be combined for speckle
      reduction with less degradation in in-plane spatial resolution than conventional
      approaches. In this paper, three-dimensional tissue motion under various strain
      conditions were simulated. It was found that significant speckle decorrelation
      existed at strains achievable in some clinical situations. Experiments were also
      conducted to test efficacy of this approach. Pulse-echo data from a gelatin-based
      phantom were acquired using a 5-MHz, single crystal transducer, and both
      conventional and compound B-mode images were formed. Results indicated that
      speckle brightness variations were reduced, and detectability of low contrast
      objects was enhanced. Performance limitations and fundamental differences between
      the proposed technique and existing techniques are discussed.

PMID- 11833891
TI  - Simulation of short LSAW transducers including electrode mass loading and finite
      finger resistance.
AB  - The theory for the 2-D numerical analysis of acoustic wave generation from finite
      length leaky surface acoustic wave (LSAW) transducer structures is presented. The
      mass loading of the electrodes is incorporated through the use of the finite
      element method (FEM). The substrate is modeled using both analytical and
      numerical means. The advantages of this simulation are twofold. First, it is
      capable of extracting the individual bulk wave conductances from the overall
      conductance of a given device. At large distances from the transducer, the
      angular distribution of power radiated relative to the substrate surface can then
      be calculated for each of the three possible bulk wave polarizations. The second
      advantage of the simulation is that the effect of finite electrode resistance is
      included through the use of a series equivalent resistance for each electrode in
      the structure. Once the resistance for each electrode in the structure has been
      determined, the overall effect on the device admittance is modeled by applying a
      constrained minimization process to the electrical boundary conditions of the
      transducer. To conclude the paper, the simulation will be compared against the
      experimental admittance of a 37-finger uniform transducer with a metalization
      ratio of 0.5 on 42 degrees LiTaO3. The agreement between theory and experiment is
      excellent.

PMID- 11833892
TI  - The influences of ambiguity phase aberration profiles on focusing quality in the
      very near field--part I: single range focusing on transmission.
AB  - Most phase aberration measurement algorithms have an ambiguity for constant and
      tilted phase aberration profiles. Based on the Fresnel (near field) approximation
      with single range focusing and the Fraunhofer (far field) approximation, constant
      and tilted phase aberration profiles change the position of the focal point only
      and do not influence the image focusing quality. Therefore, ambiguity phase
      aberration profiles are generally considered to be harmless and ignored in those
      algorithms and related theoretical analyses. However, Fresnel and Fraunhofer
      approximations may become invalid under many medical ultrasound imaging
      situations, e.g., when the imaging field is in the very near field (f-number
      approximately 1). In the very near field, although it is known that constant and
      tilted phase aberration profiles may degrade the focusing quality, it seems that
      there is a lack of quantitative analysis results in the literature about their
      influences, and this is the purpose of the current paper. In this paper, a
      quantitative analysis with a very near field approximation is performed for
      single range focusing on transmission, which is a commonly used transmission
      focusing method in medical ultrasound imaging. The tolerable levels of constant
      and tilted phase aberration profiles are derived as a function of the imaging
      system's f-number and wavelength. Because some phase aberration measurement
      algorithms may also have an ambiguity for quadratic phase aberration profiles,
      they are also included in the analysis. The theoretical results are compared with
      numerical and simulation results. These results have shown that the influences of
      tilted and quadratic phase-aberration profiles can be ignored only under certain
      conditions in the very near field.

PMID- 11833893
TI  - The influences of ambiguity phase aberration profiles on focusing quality in the
      very near field part II: dynamic range focusing on reception.
AB  - In Part I of this work, the influences of ambiguity phase aberration profiles,
      including constant, tilted, and quadratic profiles, on focusing quality have been
      quantitatively analyzed with the very near field approximation for single range
      focusing on transmission. In this paper, their influences are analyzed in a very
      different situation: dynamic range focusing on reception, which is commonly used
      in medical ultrasound imaging for beam formation on reception. It is shown that
      the results for dynamic range focusing on reception are dramatically different
      from those for single range focusing on transmission. For example, constant phase
      aberration profiles are harmless to focusing quality for single range focusing on
      transmission but become harmful for dynamic range focusing on reception. The
      analysis also shows that, compared with single range focusing on transmission,
      dynamic range focusing on reception is much more sensitive to ambiguity phase
      aberration profiles, which have adverse effects on focusing quality even in the
      near field and far field. These significant differences are caused by the
      fundamental differences between single range focusing and dynamic range focusing
      as well as between transmission and reception. Numerical and simulation results
      are also derived to test the correctness and accuracy of the theoretical results.

PMID- 11833894
TI  - Modeling of CW annular arrays using limited diffraction Bessel beams.
AB  - We present a method for characterizing the linear field of any flat, continuous
      wave annular array in terms of a set of known limited-diffraction Bessel beams.
      The technique uses Fourier-Bessel series to model the surface pressure of the
      transducer surface, with each term in the series giving rise to a Bessel beam
      with known propagation parameters. The analysis is applied numerically to two
      different transducers discussed previously in the literature. In both cases, a
      deeper understanding of the field emitted than was previously available is
      gained. Brief outlines for extending the technique to pulsed wave and non-annular
      arrays are also given.

PMID- 11833895
TI  - Acoustoelastic effect in stressed heterostructures.
AB  - Mechanical stresses influence the phase velocity of acoustic waves, known as the
      AE (acoustoelastic) effect. In order to calculate the AE effect of biaxially
      stressed layered systems, we extended the transfer matrix method for acoustic
      wave propagation by considering the change of the density, the influence of
      residual stress, and the modification of the elastic stiffness tensor by residual
      strain and by third-order constants. The generalized method is applied to the
      calculation of the angular dispersion of the AE effect for transverse bulk modes
      and surface acoustic waves on Ge(001). Our calculations reveal that the AE effect
      significantly depends on the propagation direction and can even change sign. The
      maximal velocity change occurs for transversally polarized waves propagating
      parallel to the [110] direction. For the layered Ge/Si(001) system, the AE effect
      is investigated for Love modes propagating in the [100] and [110] directions. The
      AE effect increases rapidly with increasing layer thickness and almost reaches
      its maximal value when the wave still penetrates into the unstressed substrate.

PMID- 11833896
TI  - Development of the line-focus-beam ultrasonic material characterization system.
AB  - A line-focus-beam ultrasonic material characterization (LFB-UMC) system has been
      developed to evaluate large diameter crystals and wafers currently used in
      electronic devices. The system enables highly accurate detection of slight
      changes in the physical and chemical properties in and among specimens. Material
      characterization proceeds by measuring the propagation characteristics, viz.,
      phase velocity and attenuation, of Rayleigh-type leaky surface acoustic waves
      (LSAWs) excited on the water-loaded specimen surface. The measurement accuracy
      depends mainly upon the translation accuracy of the mechanical stages used in the
      system and the stability of the temperature environment. New precision mechanical
      translation stages have been developed, and the mechanical system, including the
      ultrasonic device and the specimen, has been installed in a temperature
      controlled chamber to reduce thermal convection and conduction at the specimen. A
      method for precisely measuring temperature and longitudinal velocity in the water
      couplant has been developed, and a measurement procedure for precisely measuring
      the LSAW velocities has been completed, achieving greater relative accuracy to
      better than +/- 0.002% at any single chosen point and +/- 0.004% for two
      dimensional measurements over a scanning area of a 200-mm diameter silicon single
      crystal substrate. The system was developed to address various problems arising
      in science and industry associated with the development of materials and device
      fabrication processes.

PMID- 11833897
TI  - A carbon balance method for paper and wood products.
AB  - The approach used to track the flow of carbon sequestered in the forest through
      harvest, processing into products, and final disposition of products is
      described. The methodology is broadly flexible and applicable to forest-based
      carbon balance assessments. A carbon balance is computed across all forestland
      ownerships for the production facility of interest. The balance considers forest
      uptake, harvest, combustion of fuels, emissions from process steps and losses
      from product use, disposition and recycling. The method also allows for
      sensitivity and marginal assessments of a variety of real and hypothetical
      situations using variable assumptions. Example results for a vertically
      integrated pulp and paper mill are presented. Results suggest that integrated
      forest products facilities drawing their raw material from sustainably managed
      forests can achieve a net positive carbon balance over the product cycle. The
      amount of net carbon sequestration attributable to such facilities depends upon a
      number of factors. The most critical of these include net forest growth, the
      method for allocating the growth in forest carbon among all of those harvesting
      from the drain area of a given facility, and the use and disposal patterns for
      the paper or wood products manufactured.

PMID- 11833898
TI  - Soil carbon pools and fluxes in urban ecosystems.
AB  - The transformation of landscapes from non-urban to urban land use has the
      potential to greatly modify soil carbon (C) pools and fluxes. For urban
      ecosystems, very little data exists to assess whether urbanization leads to an
      increase or decrease in soil C pools. We analyzed three data sets to assess the
      potential for urbanization to affect soil organic C. These included surface (0-10
      cm) soil C data from unmanaged forests along an urban-rural gradient, data from
      "made" soils (1 m depth) from five different cities, and surface (0-15 cm) soil
      data of several land-use types in the city of Baltimore. Along the urban-rural
      land-use gradient, we found that soil organic matter concentration in the surface
      10 cm varied significantly (P=0.001). In an analysis of variance, the urban
      forest stands had significantly (P=0.02) higher organic C densities (kg m(-2) to
      1 m depth) than the suburban and rural stands. Our analysis of pedon data from
      five cities showed that the highest soil organic C densities occurred in loamy
      fill (28.5 kg m(-2)) with the lowest occurring in clean fill and old dredge
      materials (1.4 and 6.9 kg m(-2), respectively). Soil organic C densities for
      residential areas (15.5 +/- 1.2 kg m(-2)) were consistent across cities. A
      comparison of land-use types showed that low density residential and
      institutional land-uses had 44 and 38% higher organic C densities than the
      commercial land-use type, respectively. Our analysis shows that as adjacent land
      use becomes more urbanized, forest soil C pools can be affected even in stands
      not directly disturbed by urban land development. Data from several "made" soils
      suggests that physical disturbances and inputs of various materials by humans can
      greatly alter the amount C stored in these soils.

PMID- 11833899
TI  - Shade trees reduce building energy use and CO2 emissions from power plants.
AB  - Urban shade trees offer significant benefits in reducing building air
      conditioning demand and improving urban air quality by reducing smog. The savings
      associated with these benefits vary by climate region and can be up to $200 per
      tree. The cost of planting trees and maintaining them can vary from $10 to $500
      per tree. Tree-planting programs can be designed to have lower costs so that they
      offer potential savings to communities that plant trees. Our calculations suggest
      that urban trees play a major role in sequestering CO2 and thereby delay global
      warming. We estimate that a tree planted in Los Angeles avoids the combustion of
      18 kg of carbon annually, even though it sequesters only 4.5-11 kg (as it would
      if growing in a forest). In this sense, one shade tree in Los Angeles is
      equivalent to three to five forest trees. In a recent analysis for Baton Rouge,
      Sacramento, and Salt Lake City, we estimated that planting an average of four
      shade trees per house (each with a top view cross section of 50 m2) would lead to
      an annual reduction in carbon emissions from power plants of 16,000, 41,000, and
      9000 t, respectively (the per-tree reduction in carbon emissions is about 10-11
      kg per year). These reductions only account for the direct reduction in the net
      cooling- and heating-energy use of buildings. Once the impact of the community
      cooling is included, these savings are increased by at least 25%.

PMID- 11833900
TI  - Spatial variability of soil organic carbon in grasslands: implications for
      detecting change at different scales.
AB  - Extensive data used to quantify broad soil C changes (without information about
      causation), coupled with intensive data used for attribution of changes to
      specific management practices, could form the basis of an efficient national
      grassland soil C monitoring network. Based on variability of extensive (USDA/NRCS
      pedon database) and intensive field-level soil C data, we evaluated the efficacy
      of future sample collection to detect changes in soil C in grasslands. Potential
      soil C changes at a range of spatial scales related to changes in grassland
      management can be verified (alpha=0.1) after 5 years with collection of 34, 224,
      501 samples at the county, state, or national scales, respectively. Farm-level
      analysis indicates that equivalent numbers of cores and distinct groups of cores
      (microplots) results in lowest soil C coefficients of variation for a variety of
      ecosystems. Our results suggest that grassland soil C changes can be precisely
      quantified using current technology at scales ranging from farms to the entire
      nation.

PMID- 11833901
TI  - Effect of soil compaction on organic carbon amounts and distribution, South
      Central Iowa.
AB  - Soils on the Mormon Trail have been compacted for over 150 years. Bulk density,
      carbon, and nitrogen samples were taken in 5-cm increments to 20 cm. Bulk density
      was determined using rings of known volume; total carbon and nitrogen with a LECO
      CHN-600. Total above ground biomass (AGB) samples were collected by clipping
      vegetation within a 0.25 m2 frame and were analyzed for carbon. Statistical
      comparisons were made using a t-test (alpha = 0.05). Bulk density was higher in
      the on-trail soils from 5 to 20 cm; soil carbon and C/N ratios were higher in the
      off-trail soils from 10 to 20 cm. AGB and AGB carbon is significantly less on the
      trail. Results indicate the compacted layer on the trail alters the soil carbon
      pool by limiting additions of fresh organic matter to the soil, limiting
      vegetative production, and by "pooling" carbon additions in the upper 10 cm of
      the soil.

PMID- 11833902
TI  - Gaseous carbon dioxide and methane, as well as dissolved organic carbon losses
      from a small temperate wetland under a changing climate.
AB  - Temperate forests can contain large numbers of wetlands located in areas of low
      relief and poor drainage. These wetlands can make a large contribution to the
      dissolved organic carbon (DOC) load of streams and rivers draining the forests,
      as well as the exchange of methane (CH4) and carbon dioxide (CO2) with the
      atmosphere. We studied the carbon budget of a small wetland, located in
      Kejimkujik National Park, Nova Scotia, Canada. The study wetland was the Pine
      Marten Brook site, a poor fen draining a mixed hardwood-softwood forest. We
      studied the loss of DOC from the wetland via the outlet stream from 1990 to 1999
      and related this to climatic and hydrologic variables. We added the DOC export
      information to information from a previously published model describing CH4 and
      CO2 fluxes from the wetland as a function of precipitation and temperature, and
      generated a new synthesis of the major C losses from the wetland. We show that
      current annual C losses from this wetland amount to 0.6% of its total C mass. We
      then predicted that under climate changes caused by a doubling of atmospheric CO2
      expected between 2040 and 2050, total C loss from the wetland will almost double
      to 1.1% of total biomass. This may convert this wetland from what we assume is
      currently a passive C storage area to an active source of greenhouse gases.

PMID- 11833903
TI  - Aspect differences in above- and belowground carbon allocation: a Montana case
      study.
AB  - Aboveground net primary production (ANPP) and belowground gross primary
      production (BGPP) of all vegetation were measured in eight young, paired plots on
      a north and south aspect in western Montana. Stands of high and low overstory
      tree leaf area index (LAI) were compared. BGPP increased with ANPP, though they
      were not directly proportional. ANPP ranged from 1550 to 4400 kg C ha(-1) year(
      1) and BGPP ranged from 1360 to 3500 kg C ha(-1) year(-1). ANPP and BGPP were
      both significantly related to LAI and aspect, where both were greater on the
      north aspect at any given LAI. Litterfall represented the largest share of ANPP;
      increases in overstory biomass represented the next largest share. Soil CO2 flux
      was higher on the north aspect. We conclude that growth differences were not
      simply a matter of re-allocating carbon between root production and ANPP. Rather,
      both production and allocation were different among the sites.

PMID- 11833904
TI  - Carbon storage in northeast China as estimated from vegetation and soil
      inventories.
AB  - We have estimated the stocks of carbon in vegetation and soil in northeast China
      based on data for 122 plots from the fourth national forest inventory, and for
      388 soil profiles from the second national soil survey. The techniques of
      Geographic Information System (GIS) have been used to extrapolate site-specific
      estimates of vegetation and soil organic carbon to the entire area of northeast
      China. Our estimate indicates that the amount of carbon in vegetation and soil
      for the region are 2.81 PgC (10(15) g C) and 26.43 PgC, respectively, and that
      the area weighted average density of vegetation and soil organic carbon are 22.7
      MgC/ha and 212.7 MgC/ha, respectively. The eastern and northern parts of the
      region show much higher carbon storage than the rest of the region. Substantial
      spatial variations in vegetation and soil organic carbon across northeast China
      suggest that regional estimates on carbon stocks and fluxes should take into
      account these spatial variations. We suggest that the methodology developed can
      be used for the entire nation of China as well as other regions of the world.

PMID- 11833905
TI  - Hurricane impacts on US forest carbon sequestration.
AB  - Recent focus has been given to US forests as a sink for increases in atmospheric
      carbon dioxide. Current estimates of US forest carbon sequestration average
      approximately 20 Tg (i.e. 10(12) g) year. However, predictions of forest carbon
      sequestration often do not include the influence of hurricanes on forest carbon
      storage. Intense hurricanes occur two out of three years across the eastern US. A
      single storm can convert the equivalent of 10% of the total annual carbon
      sequestrated by US forests into dead and downed biomass. Given that forests
      require at least 15 years to recover from a severe storm, a large amount of
      forest carbon is lost either directly (through biomass destruction) or indirectly
      (through lost carbon sequestration capacity) due to hurricanes. Only 15% of the
      total carbon in destroyed timber is salvaged following a major hurricane. The
      remainder of the carbon is left to decompose and eventually return to the
      atmosphere. Short-term increases in forest productivity due to increased nutrient
      inputs from detritus are not fully compensated by reduced stem stocking, and the
      recovery time needed to recover leaf area. Therefore, hurricanes are a
      significant factor in reducing short-term carbon storage in US forests.

PMID- 11833906
TI  - Carbon accounting model for forests in Australia.
AB  - CAMFor (Carbon Accounting Model for Forests) is a sophisticated spreadsheet model
      developed to assist in carbon accounting and projection. This model can integrate
      information from a range of alternate sources including user input, default
      parameters and third party model outputs to calculate the carbon flows associated
      with a stand of trees and the wood products derived from harvests of that stand.
      Carbon is tracked in the following pools: * Biomass (stemwood, branches, bark,
      fine and coarse roots, leaves and twigs) * Soil (organic matter and inert
      charcoal) * Debris (coarse and fine litter, slash, below ground dead material) *
      Products (waste wood, sawn timber, paper, biofuel, reconstituted wood products).
      These pools can be tracked following thinning, fires and over multiple rotations.
      A sensitivity module has been developed to assist examination of the important
      assumptions and inputs. This paper reviews the functionality of CAMFor and
      reports on its use in a case study to explore the precision of estimates of
      carbon sequestration in a eucalypt plantation. Information on variability in
      unbiased models, measurement accuracy and other sources of error are combined in
      a sensitivity analysis to estimate the overall precision of sequestration
      estimates.

PMID- 11833907
TI  - Pollution mitigation and carbon sequestration by an urban forest.
AB  - At the beginning of the 1900s, the Canberra plain was largely treeless. Graziers
      had carried out extensive clearing of the original trees since the 1820s leaving
      only scattered remnants and some plantings near homesteads. With the selection of
      Canberra as the site for the new capital of Australia, extensive tree plantings
      began in 1911. These trees have delivered a number of benefits, including
      aesthetic values and the amelioration of climatic extremes. Recently, however, it
      was considered that the benefits might extend to pollution mitigation and the
      sequestration of carbon. This paper outlines a case study of the value of the
      Canberra urban forest with particular reference to pollution mitigation. This
      study uses a tree inventory, modelling and decision support system developed to
      collect and use data about trees for tree asset management. The decision support
      system (DISMUT) was developed to assist in the management of about 400,000 trees
      planted in Canberra. The size of trees during the 5-year Kyoto Commitment Period
      was estimated using DISMUT and multiplied by estimates of value per square meter
      of canopy derived from available literature. The planted trees are estimated to
      have a combined energy reduction, pollution mitigation and carbon sequestration
      value of US$20-67 million during the period 2008-2012.

PMID- 11833908
TI  - Development of a protocol for monitoring status and trends in forest soil carbon
      at a national level.
AB  - The national Forest Health Monitoring (FHM) program requires protocols for
      monitoring soil carbon contents. In a pilot study, 30 FHM plots loblolly
      shortleaf (Pinus taeda L./Pinus echinata Mill.) pine forests across Georgia were
      sampled by horizon and by depth increments. For total soil carbon, approximately
      40% of the variance was between plots, 40% between subplots and 20% within
      subplots. Results by depth differed from those obtained by horizon primarily due
      to the rapid changes in carbon content from the top to the bottom of the A
      horizon. Published soil survey information overestimated bulk densities for these
      forest sites. The measurement of forest floor depths as a substitute to sampling
      did not provide reliable estimates of forest floor carbon. Precision of replicate
      samples was approximately 10-30% for field duplicates and 5-10% for laboratory
      duplicates. Based on national indicator evaluation criteria, sampling by depth
      using bulk density core samplers has been recommended for national
      implementation. Additional procedures are needed when sampling organic soils or
      soils with a high percentage of large rock fragments.

PMID- 11833909
TI  - Using forest health monitoring data to integrate above and below ground carbon
      information.
AB  - The national Forest Health Monitoring (FHM) program conducted a remeasurement
      study in 1999 to evaluate the usefulness and feasibility of collecting data
      needed for investigating carbon budgets in forests. This study indicated that FHM
      data are adequate for detecting a 20% change over 10 years (2% change per year)
      in percent total carbon and carbon content (MgC/ha) when sampling by horizon,
      with greater than 80% probability that a change in carbon content will be
      determined when a change has truly occurred (P < or = 0.33). The data were also
      useful in producing estimates of forest floor and soil carbon stocks by depth
      that were somewhat lower than literature values used for comparison. The scale at
      which the data were collected lends itself to producing standing stock estimates
      needed for carbon budget development and carbon cycle modeling. The availability
      of site-specific forest mensuration data enables the exploration of above ground
      and below ground linkages.

PMID- 11833910
TI  - Forest inventory and analysis: a national inventory and monitoring program.
AB  - Forests provide significant commodity and noncommodity values to the citizens of
      the United States. An important and substantial role in ensuring the continued
      health, productivity, and sustainability of these resources is a reliable and
      credible inventory and monitoring program. The Forest Inventory and Analysis
      (FIA) program of the US Forest Service has been monitoring and reporting on
      status, condition, and trends in the nation's forests for over 70 years and the
      Forest Health Monitoring (FHM) program for the last 11 years. Recent legislation
      included in the 1998 Farm Bill, along with efforts to integrate inventory and
      monitoring networks to deliver Criteria and Indicators of Sustainable Forests,
      are redefining the role and operation of the recently integrated FIA and FHM
      programs. This paper provides a brief history and a look at new directions for
      the enhanced FIA Program.

PMID- 11833911
TI  - Estimating down deadwood from FIA forest inventory variables in Maine.
AB  - Down deadwood (DDW) is a carbon component important in the function and structure
      of forest ecosystems, but estimating DDW is problematic because these data are
      not widely available in forest inventory databases. However, DDW data were
      collected on USDA Forest Service Forest Inventory and Analysis (FIA) plots during
      Maine's 1995 inventory. This study examines ways to predict DDW biomass from
      other FIA variables so that DDW could be estimated without tedious measurement.
      Our results include a regression model that predicts DDW as a function of stand
      size class, basal area of dead and cut trees, and dummy variables for forest type
      and forest industry ownership. We also found DDW similar to FIA's standing-tree
      mortality at a statewide scale.

PMID- 11833912
TI  - Use of pyrolysis molecular beam mass spectrometry (py-MBMS) to characterize
      forest soil carbon: method and preliminary results.
AB  - The components of soil organic matter (SOM) and their degradation dynamics in
      forest soils are difficult to study and thus poorly understood, due to time
      consuming sample collection, preparation, and difficulty of analyzing and
      identifying major components. As a result, changes in soil organic matter
      chemical composition as a function of age, forest type, or disturbance have not
      been examined. We applied pyrolysis molecular beam mass spectrometry (py-MBMS),
      which provides rapid characterization of SOM of whole soil samples. to the
      Tionesta soil samples described by Hoover, C.M., Magrini, K.A., Evans, R.J.,
      2002. Soil carbon content and character in an old growth forest in northwestern
      Pennsylvania: a case study introducing molecular beam mass spectrometry (PY
      MBMS). Environmental Pollution 116 (Supp. 1), S269-S278. Our goals in this work
      were to: (1) develop and demonstrate an advanced, rapid analytical method for
      characterizing SOM components in whole soils, and (2) provide data-based models
      to predict soil carbon content and residence time from py-MBMS analysis. Using py
      MBMS and pattern recognition techniques we were able to statistically distinguish
      among four Tionesta sites and show an increase in pyrolysis products of more
      highly decomposed plant materials at increasing sample depth. For example, all
      four sites showed increasing amounts of older carbon (phenolic and aromatic
      species) at deeper depths and higher amounts of more recent carbon (carbohydrates
      and lignin products) at shallower depths. These results indicate that this type
      of analysis could be used to rapidly characterize SOM for the purpose of
      developing a model, which could be used in monitoring the effect of forest
      management practices on carbon uptake and storage.

PMID- 11833913
TI  - Soil carbon content and character in an old-growth forest in northwestern
      Pennsylvania: a case study introducing pyrolysis molecular beam mass spectrometry
      (py-MBMS).
AB  - This study was conducted to: (1) test the utility of a new and rapid analytical
      method, pyrolysis molecular beam mass spectrometry (py-MBMS), for the measurement
      and characterization of carbon in forest soils, and (2) examine the effects of
      natural disturbance on soil carbon dynamics. An additional objective was to test
      the ability of py-MBMS to distinguish recent from more stable humic substances,
      and to relate this information to the ecology and history of the sites. To test
      the utility of the py-MBMS technique, we investigated soil carbon stocks in a
      chronosequence of stands arising from natural disturbance in the Tionesta Scenic
      and Research Natural Areas. Soil carbon increased with increasing time since
      disturbance; although the exact shape of the carbon accumulation curve is not
      known, it appears that the rate of carbon accretion is initially rapid and then
      levels off, with a possible maximum of 86 metric tons/ha to a depth of 30 cm.
      This study also demonstrates that py-MBMS is a valid method for characterizing
      soil carbon and can be used with little sample preparation. In addition,
      multivariate analysis of the mass spectra from Tionesta soils can distinguish
      both sites and depths on the basis of their pyrolysis products; both long-lived
      and short-lived carbon forms were identified.

PMID- 11833914
TI  - The potential of diffuse reflectance spectroscopy for the determination of carbon
      inventories in soils.
AB  - Investigations have shown that near- and mid-infrared reflectance spectroscopy
      can accurately determine organic-C in soil. Efforts have also demonstrated that
      both can differentiate between organic and inorganic-C in soils, but the mid
      infrared produces more accurate calibrations. Nevertheless, the greatest benefit
      would come with in situ determinations where factors such as particle size,
      sample heterogeneity and moisture can be important. While the variations in large
      (> 20 mesh) particle size can adversely effect calibration accuracy, efforts have
      demonstrated that the scanning of larger amounts of sample can overcome this, but
      the effects of moisture have not been fully explored. While under in situ
      conditions C distribution and sample heterogeneity are a problem for any
      analytical method, the rapid analysis possible with spectroscopic techniques will
      allow many more samples to be analyzed. In conclusion, near- and mid-infrared
      spectroscopy have great potential for providing the C values needed for C
      sequestration studies.

PMID- 11833915
TI  - Productivity responses of Acer rubrum and Taxodium distichum seedlings to
      elevated CO2 and flooding.
AB  - Elevated levels of atmospheric CO2 are expected to increase photosynthetic rates
      of C3 tree species, but it is uncertain whether this will result in an increase
      in wetland seedling productivity. Separate short-term experiments (12 and 17
      weeks) were performed on two wetland tree species, Taxodium distichum and Acer
      rubrum, to determine if elevated CO2 would influence the biomass responses of
      seedlings to flooding. T. distichum were grown in replicate glasshouses (n = 2)
      at CO2 concentrations of 350 or 700 ppm. and A. rubrum were grown in growth
      chambers at CO2 concentrations of 422 or 722 ppm. Both species were grown from
      seed. The elevated CO2 treatment was crossed with two water table treatments,
      flooded and non-flooded. Elevated CO2 increased leaf-level photosynthesis, whole
      plant photosynthesis, and trunk diameter of T. distichum in both flooding
      treatments, but did not increase biomass of T. distichum or A. rubrum. Flooding
      severely reduced biomass, height, and leaf area of both T. distichum and A.
      rubrum. Our results suggest that the absence of a CO2-induced increase in growth
      may have been due to an O2 limitation on root production even though there was a
      relatively deep (approximately 10 cm) aerobic soil surface in the non-flooded
      treatment.

PMID- 11833916
TI  - Modeling above-canopy CO2 flux and evapotranspiration in wheat.
AB  - Simulations of above-canopy water vapor and CO2 fluxes were calculated by the
      USGF linked model of canopy gas exchange and subsurface processes for the 1996
      1997 winter wheat season at the AmeriFlux Wheat Site, Oklahoma. Soil surface CO2
      flux plus canopy gas exchange and transpiration plus soil evaporation modeled the
      CO2 and water vapor fluxes, respectively. Parameter values for net
      photosynthesis, respiration and transpiration were obtained from published
      sources, generated from Wheat Site data, or estimated by minimizing standard
      deviation between model and data. The mean measured downward flux of CO2 during
      rapid growth and maturity of the crop was -0.45 mg m(-2) s(-1) compared to
      simulated flux of -0.47. Simulated downward CO2 flux exceeded measured values
      during rapid growth of the crop but underestimated the flux during maturity. For
      the entire 285-day period, the mean measured upward CO2 flux at night was 0.06
      and simulated flux was 0.05.

PMID- 11833917
TI  - Anthropogenic and natural CO2 emission sources in an arid urban environment.
AB  - Recent research has shown the Phoenix, AZ metropolitan region to be characterized
      by a CO2 dome that peaks near the urban center. The CO2 levels, 50% greater than
      the surrounding non-urban areas, have been attributed to anthropogenic sources
      and the physical geography of the area. We quantified sources of CO2 emissions
      across the metropolitan region. Anthropogenic CO2 emission data were obtained
      from a variety of government and NGO sources. Soil CO2 efflux from the dominant
      land-use types was measured over the year. Humans and automobile activity
      produced more than 80% input of CO2 into the urban environment. Soil CO2 efflux
      from the natural desert ecosystems showed minimal emissions during hot and dry
      periods, but responded rapidly to moisture. Conversely, human maintained
      vegetation types (e.g. golf courses, lawns, irrigated agriculture) have greater
      efflux and are both temperature and soil moisture dependent. Landfills exhibited
      the most consistent rates, but were temperature and moisture independent. We
      estimate the annual CO2 released from the predominant land-use types in the
      Phoenix region and present a graphical portrayal of soil CO2 emissions and the
      total natural and anthropogenic CO2 emissions in the metropolitan region using a
      GIS-based approach. The results presented here do not mimic the spatial pattern
      shown in previous studies. Only, with sophisticated mixing models will we be able
      to address the total effect of urbanization on CO2 levels and the contribution to
      regional patterns.

PMID- 11833918
TI  - Particulate and non-particulate fractions of soil organic carbon under pastures
      in the Southern Piedmont USA.
AB  - Pasture management can be effective at sequestering soil organic C. We determined
      the depth distribution of particulate organic C (POC), non-particulate organic C
      (NPOC), particulate-to-total organic C (POC-to-TOC) ratio, and particulate
      organic C-to-N (POC-to-N) ratio under pastures near Watkinsville, GA, USA. POC
      was highly related with total organic C (TOC), but became an increasingly larger
      portion of TOC near the soil surface, where both pools were greatest. POC and
      NPOC were (i) greater under pasture than under conservation-tillage cropland,
      (ii) greater when pasture was grazed than when hayed, (iii) marginally greater
      with higher fertilization of pasture, (iv) greater with higher frequency of
      endophyte infection of tall fescue, and (v) greater under increasing stand age of
      grass. Soil under pasture comparisons that had greater TOC content had (i) larger
      improvements in POC than in NPOC and (ii) lower POC-to-N ratios, suggesting
      improvement in biochemical soil quality, as well as soil C sequestration.

PMID- 11833919
TI  - Soil carbon protection in podocarp/hardwood forest, and effects of conversion to
      pasture and exotic pine forest.
AB  - A combination of paired site, time series, and survey approaches were used to
      estimate the effect of land use change on mineral soil carbon (C), and to
      identify factors associated with variation. Land-uses compared included
      podocarp/hardwood forest, improved pasture, and pine plantation. Soil C was
      significantly related to soil pH that ranged between 3.9-5.9 (0-0.05 m), 3.6-6.0
      (0.05-0.10 m), and 4.5-6.1 (0.10-0.50 m) in indigenous forest. Time series data
      obtained by periodically re-sampling soil (0-0.10 m) in permanent plots in a pine
      forest previously under pasture showed that mineral soil C decrease by
      approximately 4 Mg ha(-1) by the end of the first rotation. The time series data
      compared closely with mean results obtained at paired-site throughout New
      Zealand. Soil C concentration was highly variable in all land-uses, and the
      evidence suggests that chemical stabilisation of C occurred under acid conditions
      in native forest, through complexation with Al, and that effects persisted long
      after conversion of the native forest to other land-uses. The implications of
      these findings for the design of sampling protocols for soil C are discussed.

PMID- 11833920
TI  - Regional estimation of current and future forest biomass.
AB  - The 90,674 wildland fires that burned 2.9 million ha at an estimated suppression
      cost of $1.6 billion in the United States during the 2000 fire season
      demonstrated that forest fuel loading has become a hazard to life, property, and
      ecosystem health as a result of past fire exclusion policies and practices. The
      fire regime at any given location in these regions is a result of complex
      interactions between forest biomass, topography, ignitions, and weather. Forest
      structure and biomass are important aspects in determining current and future
      fire regimes. Efforts to quantify live and dead forest biomass at the local to
      regional scale has been hindered by the uncertainty surrounding the measurement
      and modeling of forest ecosystem processes and fluxes. The interaction of
      elevated CO2 with climate, soil nutrients, and other forest management factors
      that affect forest growth and fuel loading will play a major role in determining
      future forest stand growth and the distribution of species across the southern
      United States. The use of satellite image analysis has been tested for timely and
      accurate measurement of spatially explicit land use change and is well suited for
      use in inventory and monitoring of forest carbon. The incorporation of Landsat
      Thematic Mapper data coupled with a physiologically based productivity model
      (PnET), soil water holding capacity, and historic and projected climatic data
      provides an opportunity to enhance field plot based forest inventory and
      monitoring methodologies. We use periodic forest inventory data from the USDA
      Forest Service's Forest Inventory and Analysis (FIA) project to obtain estimates
      of forest area and type to generate estimates of carbon storage for evergreen,
      deciduous, and mixed forest classes for use in an assessment of remotely sensed
      forest cover at the regional scale for the southern United States. The displays
      of net primary productivity (NPP) generated from the PnET model show areas of
      high and low forest carbon storage potential and their spatial relationship to
      other landscape features for the southern United States. At the regional scale,
      predicted annual NPP in 1992 ranged from 836 to 2181 g/m2/year for evergreen
      forests and 769-2634 g/m2/year for deciduous forests with a regional mean for all
      forest land of 1448 g/m2/year. Prediction of annual NPP in 2050 ranged from 913
      to 2076 g/m2/year for evergreen forest types to 1214-2376 g/m2/year for deciduous
      forest types with a regional mean for all forest land of 1659 g/m2/year. The
      changes in forest productivity from 1992 to 2050 are shown to display potential
      areas of increased or decreased forest biomass. This methodology addresses the
      need for spatially quantifying forest carbon in the terrestrial biosphere to
      assess forest productivity and wildland fire fuels.

PMID- 11833921
TI  - Simulated effects of dryland cropping intensification on soil organic matter and
      greenhouse gas exchanges using the DAYCENT ecosystem model.
AB  - We present evidence to show that DAYCENT can reliably simulate soil C levels,
      crop yields, and annual trace gas fluxes for various soils. DAYCENT was applied
      to compare the net greenhouse gas fluxes for soils under different land uses. To
      calculate net greenhouse gas flux we accounted for changes in soil organic C, the
      C equivalents of N2O emissions and CH4 uptake, and the CO2 costs of N fertilizer
      production. Model results and data show that dryland soils that are depleted of C
      due to conventional till winter wheat fallow cropping can store C upon conversion
      to no till, by reducing the fallow period, or by reversion to native vegetation.
      However, model results suggest that dryland agricultural soils will still be net
      sources of greenhouse gases although the magnitude of the source can be
      significantly reduced and yields can be increased upon conversion to no till
      annual cropping.

PMID- 11833922
TI  - Influence of seedling roots, environmental factors and soil characteristics on
      soil CO2 efflux rates in a 2-year-old loblolly pine (Pinus taeda L.) plantation
      in the Virginia Piedmont.
AB  - To understand the role of managed forests in carbon sequestration an
      understanding of factors controlling soil CO2 efflux will be necessary. This
      study examined the influence of seedling roots, environmental factors, nutrient
      availability, and soil characteristics on soil CO2 efflux patterns in a 2-year
      old pine plantation in the Virginia Piedmont. Efflux rates were measured both
      near the base of seedlings and midway between rows in plots that had received
      fertilization and mulch treatments in a factorial combination. Soil CO2 efflux
      rates were consistently higher near the base of seedlings, fertilization
      increased seedling growth with no significant effect on rates. and mulching
      increased winter efflux rates. In a regression analysis of seasonal soil CO2
      efflux, soil temperature explained 42.2% of the variance followed by the
      interaction of soil temperature and moisture and of soil temperature and plot
      position, which together explained an additional 9.8% of the observed variance in
      seasonal rates. During March 2000 measurements, the spatial pattern of soil CO2
      efflux between plots was most influenced by differences in soil nitrogen and pine
      root biomass. Furthermore, spatial differences observed in mean annual efflux
      rates were found to be highly influenced by the amount of soil coarse fragments
      in the upper soil profile.

PMID- 11833923
TI  - Changes in soil quality and below-ground carbon storage with conversion of
      traditional agricultural crop lands to bioenergy crop production.
AB  - Berm-isolated (0.5 ha) plots have been used since 1995 to quantify changes in
      soil and water quality with conversion from agricultural to bioenergy crops. Soil
      quality improvements, including increases in soil carbon storage, have occurred
      on sites planted to woody or herbaceous species, and no-till corn compared with
      tilled corn or cotton. Initial increases in soil carbon occurred within the upper
      10 cm of the soil profile. Soil carbon on plantings of switchgrass, no-till corn,
      and sweetgum with a cover crop between the rows increased over the first 3 years.
      Soil carbon decreased by 6% on the sweetgum plantings without a cover crop and
      remained lower through the fifth growing season. Overall, the greatest increases
      in below ground carbon storage have occurred primarily within the upper 40 cm.
      Former land use, growth characteristics, management practices, and soil
      characteristics appear to be the primary factors determining the timing, depth.
      and extent of changes in soil carbon storage for bioenergy and no-till crops.

PMID- 11833924
TI  - Building capacity for prevention's next generation.

PMID- 11833925
TI  - Parent training in head start: a comparison of program response among African
      American, Asian American, Caucasian, and Hispanic mothers.
AB  - The effectiveness of the Incredible Years Parenting Program was evaluated in a
      low-income sample of Caucasian, African American, Hispanic, and Asian mothers
      whose children were enrolled in Head Start. Data from two prior intervention
      studies [Webster-Stratton (1998) Journal of Consulting and Clinical Psychology,
      66(5), 715-730; Webster-Stratton et al. (in press) Journal of Clinical Child
      Psychology] were combined, yielding a sample of 634 families (370 Caucasian, 120
      African American, 73 Asian, 71 Hispanic) across 23 Head Start centers. Centers
      were matched and assigned randomly to either an experimental condition (8-12
      weeks of weekly 2-hr parenting classes), or a control condition (the regular Head
      Start Program without parenting groups). Families in both conditions were
      assessed using home observations of parent-child interactions and parent reports
      of parenting style and discipline strategies and child behavior problems in the
      fall (baseline) and spring (postintervention) of the children's Head Start year.
      Families were reassessed 1 year later. Following treatment, intervention mothers
      were observed to be more positive, less critical, more consistent, and more
      competent in their parenting than were control mothers. Additionally, children of
      intervention parents were observed to exhibit fewer behavior problems than were
      control children. Differences in treatment response across ethnic groups were
      few, and did not exceed the number expected by chance. Parents from all groups
      reported high satisfaction levels following the parenting program. Results
      indicate that the Incredible Years Program is accepted by and effective with
      diverse populations.

PMID- 11833926
TI  - Tai Chi, self-efficacy, and physical function in the elderly.
AB  - Using Tai Chi as an exercise mode, this study examined the association between
      self-efficacy and physical function. Ninety-four healthy, physically inactive
      older adults (M age = 72.8 years, SD = 5.1) were randomly assigned to either a 6
      month, twice a week, Tai Chi condition or a wait-list control condition. Outcome
      variables included self-reports of movement efficacy and physical function
      assessed at baseline, middle, and termination of the study. Multisample latent
      curve analyses revealed a significant rate of change attributable to the Tai Chi
      intervention in both self-efficacy and physical function, with participants
      experiencing significant improvements over the course of the intervention.
      Analyses also showed a positive association between self-efficacy and physical
      function, indicating that improvements in older adults' self-efficacy of movement
      as a function of Tai Chi were related to increased levels of perceived physical
      capability. This study uncovered the need for further exploration of the
      relationship between exercise self-efficacy and physical function for enhancing
      health-related quality of life in older adults.

PMID- 11833927
TI  - Impact of parental substance use disorder and child neglect severity on substance
      use involvement in male offspring.
AB  - Two child self-report scales were developed to measure parental neglect
      (emotional distance and parental involvement) in a sample of 344 boys between 10
      and 12 years of age. Psychometric analyses of the parental emotional distance and
      involvement scales demonstrated their unidimensionality; construct, concurrent,
      and predictive validity; and reliability. Cross-sectional analyses indicated that
      neglect was more severe among boys who had a parent with a DSM-III-R lifetime
      substance use disorder (SUD) compared to youth whose parents had no Axis I
      psychiatric disorder. In addition, children reported more severe neglect by the
      mother than the father. Longitudinal analyses of a subsample (n = 99) revealed
      that child neglect at ages 10-12 predicted significant variance on a composite
      measure of substance use involvement and severity of substance use as well as
      increased the risk for SUD at age 19.

PMID- 11833928
TI  - A meta-analytic inquiry into the relationship between selected risk factors and
      problem behavior.
AB  - Identifying the predictors of problem behavior is essential both for
      understanding the causes of such behavior and for preventing it. Although a great
      deal of research has sought to identify the factors predictive of problem
      behavior, much of the research to date has been correlational and tells us little
      about causality. This study attempts to improve on the correlational research by
      applying meta-analytic techniques to existing experimental and quasi-experimental
      studies of school-based prevention. The following 3 risk factors were examined:
      academic performance, bonding to school, and social competency skills. The most
      convincing evidence of a relationship between risk and problem behavior was found
      for bonding to school. Positive changes in attachment and commitment to school
      resulting from the preventive interventions were consistently accompanied by
      positive changes in problem behavior. Preventive interventions that produced
      improvements in academic performance produced moderate improvements in problem
      behavior. With regard to social competence, the association depended in large
      part on the type of measure used to assess social competency skills. Changes in
      self-report measures of social competency were unrelated to changes in problem
      behavior, whereas a strong positive correlation was observed between changes in
      ratings and observations of social competency by others and improvements in
      problem behavior.

PMID- 11833929
TI  - Modelling reproduction in farm animals: a review.
AB  - During the last few decades, our knowledge of the biology of the reproductive
      system has improved significantly and also become more quantitative. In parallel,
      there has been an increase in the development of mathematical models, as both
      research tools and management tools, that can integrate our knowledge of
      reproductive events and then attempt to predict reproductive efficiency. This
      review considers these modelling approaches according to the level of
      organization that they address, from representation of the dynamic functions of
      the reproductive axis to the prediction of reproductive performance of a flock or
      herd. We emphasize the contribution of modelling to the exploration and
      understanding of a complex system-a system that responds to a host of internal
      regulatory mechanisms as well as to an array of external factors such as
      nutrition, photoperiod and sociosexual signals. To date, models have proven
      useful for depicting the kinetics of some of the endocrine signals that are
      implicated in perturbations of the reproductive axis and they have also been
      successful in the exploration of ovarian dynamics during the oestrous cycle.
      However, two areas are still largely unexplored by biomathematical models: the
      dynamic links between the different stages of the reproductive life of an animal,
      and mechanistic influences of environmental factors on the reproductive axis.

PMID- 11833930
TI  - Effect of commercially available PMSG on maturation, fertilization and embryo
      development of buffalo oocytes in vitro.
AB  - In vitro fertilization (IVF) technology provides an opportunity to produce
      embryos for genetic manipulation, embryo transfer and basic research in
      developmental physiology, and can be exploited for emerging biotechnologies such
      as transgenesis and cloning. In the present study, the effects of different
      concentrations of commercially available pregnant mare serum gonadotrophin (PMSG)
      (Folligon; Intervet, International B.V, Boxmeer, Holland) in oocyte culture
      media, on maturation, fertilization and embryonic development of buffalo oocytes
      in vitro were investigated. Oocytes aspirated from abattoir-derived ovaries were
      cultured in media containing TCM-199 + PMSG at 0, 2.5, 20, 30, 40 and 50 IU mL(
      1) in presence or absence of steer serum (10%) for 24 h in a CO2 incubator. The
      maturation rate was assessed on the basis of degree of expansion of cumulus
      cells. The matured oocytes were inseminated with 9-10 x 10(6) spermatozoa mL(-1)
      in Brackett and Oliphant medium and the cleavage rate was recorded 40-42 h after
      insemination. Uncleaved oocytes were stained with aceto-orcein for evaluation of
      fertilization rates. The cleaved embryos were further cultured in TCM-199 + 10%
      steer serum on buffalo oviducal cell monolayer for 7 days. Maturation,
      fertilization, cleavage and embryonic development were significantly higher (P <
      0.05) in oocytes cultured in TCM-199 + 10% steer serum supplemented with 40 and
      50 IU PMSG mL(-1). It is concluded that commercially available PMSG can
      effectively be used in place of pure follicle-stimulating hormone for in vitro
      maturation of buffalo oocytes, making it cost effective for IVF studies.

PMID- 11833931
TI  - Influence of glucose on the sex ratio of bovine IVM/IVF embryos cultured in
      vitro.
AB  - The effect of glucose in the medium used during in vitro culture on the sex ratio
      of bovine blastocysts derived from in-vitro-matured and in-vitro-fertilized
      oocytes was evaluated. Oocytes were matured and inseminated with mixed sperm from
      three bulls and were cultured in vitro in modified synthetic oviducal fluid
      medium with 10% fetal calf serum, with or without glucose supplementation. The
      overall rate of cleaved embryos that developed to expanded blastocyst in the
      medium without glucose (27.0%) was significantly greater (P < 0.05) than the
      percentage observed when embryos were cultured in medium with glucose (17.5%).
      Analysis of variance was performed to analyse the effect of glucose on the
      proportion of male embryos reaching the blastocyst stage (or arrested at the
      morula stage) during Days 7 to 10. Regardless of the presence or absence of
      glucose in the medium, significantly (P < 0.05) more male than female embryos
      were harvested as expanded blastocysts on Day 7 and on Day 8 of culture. On Days
      9 plus 10 of culture, a sex ratio imbalance only occurred in the absence of
      glucose in the culture medium (P < 0.05). Glucose did not produce any significant
      effect on the sex ratio of the overall number of expanded blastocysts harvested
      by Day 10 of in vitro culture. However a significantly greater proportion of
      females (P < 0.01) were found among those embryos that developed only to the
      morulae stage after 10 days in vitro. These results show that glucose
      supplementation of culture media produces a preferential loss of female embryos
      during culture to the blastocyst stage.

PMID- 11833933
TI  - Ovulation in the tree shrew (Tupaia belangeri) induced by gonadotrophins.
AB  - The induction of ovulation by exogenous gonadotrophins is an important approach
      for recovering oocytes used for studies on the reproductive biology of some
      mammals. In the present study, pregnant mare serum gonadotrophin (PMSG) and human
      chorionic gonadotrophin (hCG) were used to induce ovulation in the tree shrew
      (Tupaia belangeri) using the following regimens. Groups A1-A3, multiple
      injections of PMSG (30-60 IU) followed by a single dose of hCG (30-60 IU); B1,
      combination of a single injection of PMSG (60 IU) with a single dose of hCG (60
      IU); E1, combination of a single injection of PMSG (60 IU) with a single dose of
      hCG (30 IU) plus PMSG (30 IU); and administration of either PMSG (C1 and C2) or
      hCG (D1). The ovulation rate of animals producing oocytes with either first polar
      body or distinct perivitelline space, and the mean number of oocytes per animal
      were considered the most important criteria in each regimen. The most effective
      induction of ovulation was achieved in groups B1 and E1, with ovulation rates of
      4/4 and 4/4, respectively, and mean numbers of ovulated oocytes per animal of
      3.25 +/- 0.48 and 4.00 +/- 0.71 respectively. No ovulation was observed in the
      control group or in group D1. Therefore, regimes B1 and E1 were considered as the
      simplest and most effective for the induction of ovulation in the tree shrew.

PMID- 11833932
TI  - Identification and regulation of the platelet-activating factor acetylhydrolase
      activity in the mouse uterus in early pregnancy.
AB  - Platelet-activating factor (PAF) is a product of the embryo and the endometrium
      in early pregnancy. The actions of PAF may be regulated by its degradation and
      this is largely achieved by the enzyme PAF acetylhydrolase (PAF:ah; EC 3.1.1.47).
      The present study characterized the PAF:ah in the endometrium and uterine fluid
      of mice during early pregnancy. The enzyme activity from uterine endometrium and
      luminal fluids had the same biochemical characteristics as the plasma form of the
      enzyme. The three sources of enzyme activity (i) had an apparent native molecular
      mass greater than 10(6) Da, but this was reduced after detergent treatment and
      purification to 60-65 kDa; (ii) bound to cholesterol hemisuccinate agarose
      matrix; and (iii) were found in the high density lipoprotein-enriched fraction
      after density gradient ultracentrifugation. In castrate females, oestradiol
      17beta (E2) caused a dose-dependent increase in the activity of the enzyme in
      endometrium and luminal fluid. Progesterone (P4) inhibited the E2-induced
      increase in PAF:ah in uterine tissue. Treatment with E2 alone caused an increase
      in endometrial PAF:ah activity within 24 h, which declined within 48 h. In
      luminal fluid, the same treatment caused increased activity within 24 h, peaking
      after 48 h of treatment and then declining. In E2-treated castrate females, mRNA
      for an intracellular (but not plasma) form of PAF:ah was detected, yet the
      intracellular form was not detected biochemically. The results suggest that most
      of the enzyme activity was not produced locally, but probably resulted from the
      influx of the plasma form of the enzyme.

PMID- 11833934
TI  - Effect of centrifugation on early embryonic development and parthenogenetic
      activation of bovine oocytes matured in vitro.
AB  - This study examined the fertilization, early developmental competence and
      capacity for parthenogenetic activation of bovine oocytes matured in vitro after
      centrifugation. Immature oocytes were cultured in tissue culture medium 199
      supplemented with 10% fetal bovine serum and 75 mIU mL(-1) FSH + LH at 5% CO2 to
      facilitate maturation. After culture for 24 or 30 h, the metaphase-II stage
      oocytes were centrifuged at 3000, 5000, 7000 or 10000g for 5 min before in vitro
      fertilization or parthenogenetic activation. Frozen-thawed bull semen was used
      for in vitro fertilization. For parthenogenetic activation, the oocytes were
      exposed to 20 microM calcium ionophore A23187 for 5 min at room temperature.
      Fertilization rates were not different between control and treatment groups
      (87.7% v. 74.6%, 73.4%, 75.9% and 76.4% respectively). Also, there were no
      differences in early embryonic development between control and treatment groups
      (rates of blastocyst formation were 21.1% v 20.2%, 28.8%, 31.2% and 24.1%
      respectively). When the oocytes were centrifuged at various speeds alone, the
      activation rate of oocytes was significantly higher (P < 0.05) in the 10000g
      treatment group compared with control (10.8% v 0.0%). There were no differences
      in the activation rates of oocytes between control and treatment groups at speeds
      up to 7000g (70.9% v. 71.9%, 78.3% and 77.2% respectively) after centrifugation
      and stimulation with Ca(2+)-ionophore. However, the activation rate of oocytes
      was significantly higher (P < 0.05) in the 10000g treatment group compared with
      control (70.9% v. 83.1%). In addition, the percentage of activated oocytes with
      diploid formation was significantly higher in the oocytes after centrifugation at
      10000g and stimulation with calcium ionophore A23187 than in the control (18.4% v
      7.1%). These results indicate that centrifugation of oocytes matured in vitro has
      no detrimental effect on fertilization and subsequent early embryonic
      development. They also indicate that the oocytes might be parthenogenetically
      activated after centrifugation and that high-speed centrifugation may induce
      activation of some oocytes. The results suggest that the optimal speed for
      centrifugation of bovine oocytes might be < or = 7000g to enhance the visibility
      of nuclear elements for further micromanipulation.

PMID- 11833935
TI  - Comparison of the effects of in vitro and in situ storage on the viability of
      mouse ovarian tissue collected after death.
AB  - Ovarian tissues, collected or salvaged from endangered species at the time of
      gonadectomy or following their death, are being transported to genebanks for
      storage with the assumption that they will (subsequently) yield sufficient
      numbers of germ cells to help preserve the species. The present study aimed to
      quantify the impact of delays in collecting and/or processing ovarian tissue on
      the number of follicles in this tissue that remained normal after grafting. The
      study compared the viability of ovarian tissue stored in vitro (in phosphate
      buffered saline) versus in situ (in the body) either on ice or at room
      temperature for 0 (non-stored fresh grafts), 3, 6, 12, 24 or 48 h. The conditions
      of storage had significant effects on the total number of morphologically normal
      follicles, with significantly more follicles in grafts developing from in vitro
      stored tissue than in situ-stored tissue. Storage temperature and duration of
      storage, but not the storage temperature alone, influenced follicle survival.
      Tissue that was grafted immediately after collection (0 h) was best, but normal
      follicles were recovered in grafts stored in vitro (on ice or at room
      temperature) or in situ (on ice only) for up to 48 h before grafting. The rate of
      follicle loss over time was very rapid, with approximately 50% fewer follicles in
      grafts derived from tissue stored for only 3 h compared with non-stored fresh
      grafts (0 h). The results show that viable ovarian tissue can be salvaged from
      animals up to 48 h after death; however, in order to best protect the follicle
      population, the ovaries should be removed from the animal's body as soon as
      possible.

PMID- 11833936
TI  - Inhibitors of caspase homologues suppress an apoptotic phenotype in cultured
      rabbit corpora lutea.
AB  - Apoptosis is a morphologically defined type of cell death initiated by various
      stimuli that results in the activation of caspases (cysteine-containing aspartate
      specific proteases). In the present study, it was determined that caspases are
      present during, and play a role in, corpus luteum (CL) apoptosis in vitro.
      Pseudopregnancy was induced in rabbits with 100 IU human chorionic gonadotrophin.
      On Day 11 of pseudopregnancy, CL were isolated and cultured for 0, 2, 4, 6, and 8
      h in the absence of trophic support to induce spontaneous apoptosis. Total RNA
      was extracted and analysed for caspase-I expression by Northern blot analysis.
      The results demonstrated caspase-I expression from 4 h. In the second part of the
      study, CL were incubated without trophic support for 4 h with increasing
      concentrations of three general caspase inhibitors, sodium aurothiomalate (SAM),
      iodoacetic acid (IAA) and N-tosyl-L-phenylalanylchloromethylketone (TPCK), and
      two specific caspase inhibitors, N-acetyl (Ac)-Tyr-Val-Ala-Asp (YVAD)
      chloromethylketone (CMK) (Ac-YVAD-CMK) and Ac-Asp-Glu-Val-Asp (DEVD)-aldehyde
      (CHO) (Ac-DEVD-CHO). At completion, DNA was isolated and integrity assessed.
      Treatment of CL with SAM, IAA or Ac-DEVD-CHO effectively suppressed apoptotic DNA
      fragmentation. The final component of the study was to examine caspase-3 protein
      expression. Western blot analysis revealed a significant increase in caspase-3
      expression over the experimental time-course. The results of the present study
      clearly demonstrate a time-dependent link between the caspases, specifically
      caspase-3 and spontaneous apoptosis in the rabbit CL.

PMID- 11833937
TI  - The future fertility of mankind: effects on world population growth and
      migration.
AB  - The world's population, currently just over 6 billion, is projected to increase
      to 9-10 billion by the year 2050. Most of this growth will occur in the
      developing countries of Asia, where there is an enormous unmet demand for
      contraception, while an increasing number of developed countries will have
      declining populations. The human immunodeficiency virus (HIV) pandemic will
      target developing countries, with India destined to become its new epicenter. By
      2050, there may be 1 billion HIV-infected people in the world. The significant
      protective effect of male circumcision may spare Islamic countries, such as
      Pakistan, Bangladesh, Iran and Indonesia, from the worst effects of the pandemic.
      Australia will be increasingly threatened by the high rates of population growth
      of her Asian neighbours. This, coupled with political instability and sea-level
      rises as a consequence of global warming, will turn the present trickle of
      refugees from a variety of Asian countries seeking safe haven on our sparsely
      populated northern coastline into a veritable flood. There will come a time when
      we have neither the manpower, nor the means, nor even the moral right to
      intercept, detain or repatriate the thousands who will come in peace, in search
      of a better life. However, if Australia is to stabilize its future population at
      around 23 million, which seems highly desirable on ecological grounds, then the
      net immigration rate must be limited to approximately 50000 people per year.
      Because the final point of departure for all these refugees is Indonesia, it is
      essential that Australia maintains good relations with Indonesia, so that
      together we can attempt to manage the refugee problem. However, Indonesia's own
      population is destined to increase by 100 million in the next 50 years, which
      will only exacerbate the situation. Australia would be well advised to make a
      major increase in its paltry financial assistance to Indonesia's excellent family
      planning programmes, which are currently starved of funds. Helping Indonesia to
      contain its population growth is Australia's best long-term investment for its
      own future.

PMID- 11833938
TI  - Regulation of metalloproteinases by nitric oxide in human trophoblast cells in
      culture.
AB  - The process of embryo implantation requires extensive remodelling of the
      endometrial extracellular matrix, a function largely performed by matrix
      degrading metalloproteinases (MMPs). In the present study, we used trophoblast
      cells isolated from human term placentas to study the regulation of MMPs by
      nitric oxide (NO). Using a combination of zymography, Western blot and indirect
      immunofluorescence, we showed that MMP-2 and MMP-9 are increased during the
      conversion from low-motile cytotrophoblast cells to the highly motile and
      differentiated syncytiotrophoblast multinucleated cells. We also observed an
      increase in NO production and NO synthase (NOS) expression during this cellular
      differentiation process. In addition, we demonstrated a positive regulatory role
      of NO on the activity and protein expression of MMP-2 and MMP-9, because NO
      donors (NOC-18 and spermine-NONOate) or the NOS substrate (L-arginine) stimulate,
      whereas NOS inhibitors (N(G)-nitro-L-arginine methyl ester and N(G)-monomethyl-L
      arginine) reduce the expression and gelatinolytic activity of MMP-2 and MMP-9 in
      isolated trophoblast cells. Taken together, these results suggest that, in
      differentiating trophoblasts, NO regulates the induction of matrix-degrading
      proteases required for invasion during embryo implantation.

PMID- 11833939
TI  - Immunolocalization of retinol-binding protein, cellular retinoic acid-binding
      protein I and retinoid X receptor beta in the porcine reproductive tract during
      the oestrous cycle.
AB  - Retinoid-binding proteins and nuclear receptors are expressed in the reproductive
      tissues of different species and their expression is hormonally regulated. In the
      present study, we demonstrated immunocytochemically the temporal and spatial
      localization of retinol-binding protein (RBP), cellular retinoic acid-binding
      protein I (CRABPI) and retinoid X receptor beta (RXRbeta) in porcine ovary,
      oviduct and uterus during the oestrous cycle. RBP and CRABPI were localized in
      the cytoplasm, whereas RXRbeta occurred in the nucleus. RBP was not detected in
      either the ovary or the oviduct at any stage of the oestrous cycle. CRABPI was
      present in luteal cells of the ovary only during dioestrus and in glandular and
      ciliated cells of the oviduct during oestrus. In the ovary, RXRbeta was always
      present in granulosa cells and germinal epithelium, with highest levels observed
      during oestrus. In the uterus, RXRbeta was present throughout the cycle in both
      the endometrium and the myometrium. However, changes in RXRbeta were observed in
      the endometrium, with highest levels observed during dioestrus. RBP and CRABPI
      could be observed in the endometrium only during dioestrus. The results show that
      the occurrence of retinoid-binding proteins and nuclear receptors in individual
      tissues of the reproductive tract are strongly dependent on the stage of the
      oestrous cycle. In the oviduct, the expression of CRABPI seems to be dependent on
      oestrogen, whereas in the uterus the expression of RBP and CRABPI is influenced
      by progesterone. The association of expression in different sections of the
      reproductive tissues investigated shows that the presence of specific proteins
      involved in retinoid metabolism was dependent on events associated with
      ovulation, the migration of the oocyte through the oviduct and the possible
      implantation of the blastocyst into the uterus.

PMID- 11833940
TI  - Serum-soluble human leucocyte antigen class I and class II concentrations as an
      alternative diagnostic test for determining immune indices required for normal
      pregnancies.
AB  - The levels of maternal immunostimulation (required throughout the gestation
      period) and immunosuppression (needed from the 8th week to labour), as assessed
      by the mixed lymphocyte reaction (MLR), have been successfully correlated with
      the outcome of pregnancy. Our laboratory has recently reported that serum-soluble
      human leucocyte antigen (HLA) class I and II concentrations can be predictive for
      successful pregnancy outcome. In fact, there is a direct correlation between
      soluble class II concentrations and maternal immunostimulation because, as
      expected, these serum HLA concentrations are augmented in the first and second
      trimester of pregnancy and remain stable thereafter. By the same token, serum HLA
      class I concentrations are low during the first trimester, correlating with the
      required absence of immunosuppression, whereas they increase in subsequent
      trimesters as suppression becomes desirable for counteracting the maternal
      stimulation, which may otherwise become dangerous to the fetus. In this study, we
      present biological and statistical evidence that both states of maternal
      immunostimulation and immunosuppression, reflected by serum soluble HLA class II
      and class I antigens, do correlate with results obtained by standard MLR and can
      be predictive of pregnancy failure. The establishment of statistically
      significant correlations renders the measurement of soluble HLA a reliable test
      for determining the immunological status of the gestating woman. The unambiguous
      advantage of such an approach is that soluble HLA testing will no longer require
      the 1 week delay necessary to obtain MLR results, a period occasionally crucial
      for applying treatment to women whose immunological indices call for immediate
      therapeutic intervention.

PMID- 11833941
TI  - Effects of caffeine and its reactive metabolites theophylline and theobromine on
      the differentiating testis.
AB  - A previous study in the rat (Pollard et al. 1990) established that caffeine, when
      administered during pregnancy, significantly inhibited the differentiation of the
      seminiferous cords and subsequent Leydig cell development in the interstitium.
      However, that study could not distinguish between the direct effects of caffeine
      and/or the intermediary secondary toxic effects of metabolites such as
      theophylline and theobromine. Because the fetus lacks the appropriate enzyme
      systems, clearance of toxic substances takes place via the placenta and maternal
      liver. Thus, a suitable in vitro system can effectively differentiate between
      primary and secondary drug effects. In the present study, 13-day-old fetal
      testis, at the stage of incipient differentiation, were cultured for 4 days in
      vitro in the presence of graded doses of caffeine, theophylline or theobromine.
      It was found that explants exposed to caffeine or theobromine differentiated
      normally, developing seminiferous cords made up of Sertoli and germ cells, soon
      followed by the differentiation of functionally active Leydig cells appearing in
      the newly formed interstitium. However, explants exposed to theophylline failed
      to develop seminiferous cords and, as a consequence, Leydig cells. In conclusion,
      insights obtained from different experimental methods, such as organ culture or
      whole organism studies, are not always identical. It may be prudent, therefore,
      to take into account that certain experimental techniques, despite providing
      valuable information, may require confirmation by other test methods in order to
      obtain an in-depth understanding of mechanisms of action involved.

PMID- 11833942
TI  - Alteration of goat sperm ecto-phosphoprotein phosphatase activity and its
      distribution on the sperm surface during epididymal maturation.
AB  - Phosphoprotein phosphatase (ecto-PPase) of goat epididymal sperm outer surface
      showed a significant increase in its activity at the initial stage of epididymal
      sperm maturation (up to the proximal corpus region) followed by a sharp fall
      towards the terminal phase of the maturation event. PPase activity showed nearly
      the same profile when estimated in intact cells as well as in isolated sperm
      plasma membrane. The ecto-PPase was purified to apparent homogeneity by using
      various biochemical fractionation procedures, such as solubilization with Triton
      X-100, sephadex gel filtration chromatography, concanavalin A-sepharose affinity
      chromatography and diethylaminoethyl-cellulose ion-exchange chromatography. The
      isolated PPase has a molecular mass of approximately 36 kDa and an isoelectric
      point of 5.95. Sperm surface topography of the enzyme was investigated using
      fluorescein isothiocyanate-conjugated antibody of the purified PPase. The
      immunofluorescent studies have demonstrated that the isolated PPase is localized
      on the external surface of viable sperm. Immunocytochemical studies also revealed
      a marked topographical alteration of ecto-PPase during epididymal transit of the
      male gametes. Immunoreactivity was observed all over the surface of caput sperm,
      but was restricted primarily to the anterior tip of the head in the corpus sperm
      and to the posterior part of the head in cauda sperm cells. The maturation
      dependent decrease in PPase activity was also confirmed by immunofluorescent
      studies. This remarkable maturation-dependent modification of ecto-PPase
      activity, as well as its distribution on sperm surface, suggest that the ecto
      enzyme may play an important role in sperm function by regulating the
      phosphorylation states of the membrane-associated and reproductive fluid
      phosphoprotein substrates.

PMID- 11833943
TI  - Improvements in the recognition and treatment of depression and decreasing
      suicide rates.

PMID- 11833944
TI  - Changing drugs--only when necessary.

PMID- 11833945
TI  - Career and life experiences of New Zealand women medical graduates.
AB  - AIMS: To investigate the career and life experiences of a cohort of women
      graduating from a New Zealand medical school. METHODS: A questionnaire was mailed
      to 415 women who had graduated from the University of Auckland between 1973 and
      1997. RESULTS: The response rate was 74%. Compared with a study undertaken in
      1986, more women are entering clinical specialties and significantly fewer
      entering general practice. 60% had children (mean 2.3 children per participant).
      The majority of women had managed to work part-time in their careers. Income per
      hour was lower for those who chose specialties to fit in with family commitments.
      Job satisfaction was moderately high, but varied between specialties. Over half
      were undecided about their specialty at graduation. CONCLUSIONS: A higher
      proportion of women is moving into specialties other than general practice. As
      about half of all medical graduates are women, most of whom will want to have
      children, training agencies and employers should continue to develop their
      programmes and jobs to facilitate the combination of work and family life.

PMID- 11833946
TI  - A survey of job satisfaction, sources of stress and psychological symptoms among
      New Zealand health professionals.
AB  - AIM: To assess job satisfaction, job-related stress and psychological morbidity
      among New Zealand physicians, surgeons and community pharmacists and provide a
      comparison with New Zealand general practitioners (GPs). METHODS: 411 physicians,
      330 surgeons and 400 randomly sampled community pharmacists, were surveyed.
      Psychological morbidity was assessed by the General Health Questionnaire (GHQ-12)
      and job satisfaction by the Warr Cook Wall scale. RESULTS: Response rates were
      70.5% for physicians, 69% for surgeons and 76% for community pharmacists. Job
      satisfaction scores for surgeons were similar to scores for GPs. Pharmacist and
      physicians scores were lower. Job satisfaction varied according to gender, the
      relative amount of time spent in public practice and the perceived ill effects of
      work on health. Pharmacists had the highest number of cases with significant
      scores on the GHQ-12 scale, with physicians and surgeons scoring similar to GPs.
      In each of these health professional groups approximately 10% described a level
      of symptoms that is associated with more severe psychological disturbance.
      CONCLUSIONS: All three groups were generally satisfied with their jobs.
      Pharmacists were significantly less so. Physicians and surgeons reported similar
      levels of psychological morbidity to GPs, which have been previously reported as
      a cause for concern.

PMID- 11833947
TI  - Persistence and perceived consequences of cannabis use and dependence among young
      adults: implications for policy.
AB  - AIMS: To document patterns of cannabis use and dependence from late-adolescence
      through to the mid-twenties; to describe perceived consequences of cannabis use
      among young people; and to consider policy implications of these findings.
      METHODS: This was a longitudinal study of the Dunedin Multidisciplinary Health
      and Development Study birth cohort with repeated measures of cannabis use at ages
      18, 21 and 26 years. RESULTS: Twelve month prevalence rates of cannabis use (just
      over 50%) and dependence (just under 10%) remained stable between age 21 and 26
      years, contrary to an expected decline. Cannabis dependence, as distinct from
      occasional use, was associated with high rates of harder drug use, selling of
      drugs and drug conviction. Cumulatively, almost 3/4 of our cohort had tried
      cannabis by age 26. Young people thought the risk of getting caught using
      cannabis was trivial, and that using cannabis had few negative social
      consequences. CONCLUSIONS: The persistent high rates of cannabis use and
      dependence among young New Zealand adults raises important issues for policy
      makers. Current laws are not particularly effective in deterring use. Whereas
      occasional use does not appear to present a serious problem, cannabis dependence
      among users is a serious public health issue that warrants immediate action.

PMID- 11833948
TI  - Does a delay in transfer to a rehabilitation unit for older people affect outcome
      after fracture of the proximal femur?
AB  - AIMS: To detemine the relationship between delay in transfer to rehabilitation
      wards and outcome for patients aged over 75 years with fracture of the proximal
      femur. METHODS: An observational study in a district general hospital of all
      patients admitted to hospital aged over 75 years with fracture of the proximal
      femur over 3 1/2 years. Outcome data collected included the number of patients
      discharged back to their usual residence and total hospital length of stay
      related to age, gender, usual residence and delay in transfer to a rehabilitation
      ward. RESULTS: 58% of 455 patients were transferred to a rehabilitation ward. For
      those patients who were transferred to a rehabilitation ward only age predicted
      discharge to a more dependent residence. The relative risk for discharge to a
      more dependent residence for people aged over 85 years compared to younger people
      was 1.47 (95% CI 1.15-1.88). Delay in transfer to rehabilitation was associated
      with a longer total hospital length of stay of 0.64 (95% CI 0.23-1.05) days per
      day of delay in transfer. CONCLUSIONS: Delay in transfer to a rehabilitation ward
      was associated with a disproportionate increase in total hospital length of stay
      for patients aged over 75 with fracture of the proximal femur.

PMID- 11833949
TI  - A survey of attitudes to parent-doctor conflicts over treatment for children.
AB  - AIMS: To investigate professional and public attitudes to the intervention of the
      law when parents and doctors disagree about the medical treatment of children.
      METHODS: A cross-sectional survey of academic staff at the University of Otago.
      Random samples of academic medical practitioners and non-Health Sciences academic
      staff completed written questionnaires, including open and closed questions.
      Questions focussed on the Liam Williams-Holloway (W-H) and Tovia Laufau (TL)
      cases. RESULTS: The response rate was 107/164 (65%) of eligible staff. Support
      for doctors seeking treatment orders was strong (77% in the W-H case, and in the
      TL case, 70% believed an order should have been sought). Women were less likely
      than men to support a treatment order, significantly in the W-H case. There were
      no significant differences between medical and non-medical respondents. Court
      processes were viewed as confrontational and a last resort only after mediation
      failed. Scientific evidence was rated as the most important consideration in
      treatment decisions, followed by likely outcome, establishment of trust between
      parents and doctors, and the age of the child. CONCLUSIONS: Among this highly
      educated group there was strong support for seeking treatment orders in the
      child's best interests. But various mediation options were preferred and should
      be explored further. More evidence is needed on the success of treatment orders
      and on the attitudes of a more representative sample of the population.

PMID- 11833950
TI  - Change from propylthiouracil to carbimazole proves fatal.

PMID- 11833951
TI  - Undergraduate medical education.

PMID- 11833952
TI  - Diabetes in New Zealand: too many, too late!

PMID- 11833953
TI  - Meningococcal vaccine.

PMID- 11833954
TI  - Liability of health professionals for a breach of the abortion law of New
      Zealand.

PMID- 11833955
TI  - Sponsorship, authorship and accountability.

PMID- 11833956
TI  - Sponsorship, authorship and accountability.

PMID- 11833957
TI  - Sponsorship, authorship and accountability.

PMID- 11833958
TI  - Sponsorship, authorship and accountability.

PMID- 11833959
TI  - Sponsorship, authorship and accountability.

PMID- 11833960
TI  - Sponsorship, authorship and accountability.

PMID- 11833961
TI  - Sponsorship, authorship and accountability.

PMID- 11833962
TI  - Mistakes, errors and wrongdoing.

PMID- 11833963
TI  - Slipped capital femoral epiphysis: more New Zealand cases likely as obesity rises
      in children and adolescents?

PMID- 11833964
TI  - Health of farmers in Southland.

PMID- 11833965
TI  - Early diagnosis?

PMID- 11833966
TI  - New Zealand's first pacemaker.

PMID- 11833967
TI  - Perinatal database.

PMID- 11833968
TI  - Antimicrobial susceptibility of Campylobacter species.

PMID- 11833969
TI  - Diffusion reconsidered: variation and transformation in biomedical practice, a
      case study from Mexico.
AB  - This paper focuses on biomedical transformations in an economically developing
      nation and poses the question, what are the variant and invariant aspects of
      biomedical practice, using empirical data from Mexico? I propose that when
      infectious disease predominated, biomedicine may have been uniformly practiced
      the world over, but with the ascent of chronic disease of unknown etiology,
      certain aspects of biomedical practice, especially diagnoses and causality,
      become reinterpreted culturally and idiosyncratically. The findings of the case
      study also illuminate current theories of globalization and earlier
      anthropological theories of diffusion as well as issues concerning the social
      constructivist perspective.

PMID- 11833970
TI  - Mixed blessings: cervical cancer screening in Recife, Brazil.
AB  - This study examines the effects of a large-scale cervical cancer prevention
      campaign in Recife, Brazil between 1994 and 1995. It suggests that while this
      program effectively motivated women to get pap smears, it reinforced local
      understandings of the pap smear that ultimately had unintended negative
      consequences for women's health. It argues that because the campaign connected
      female sexual activity directly with cervical cancer, the program's message was
      interpreted by many women to mean that cervical cancer was a sexually transmitted
      disease and that it would behave like one. Women who were no longer sexually
      active believed that they did not need to be screened. In addition, women who
      were sexually active believed that they could use pap smears to diagnose and cure
      sexually transmitted diseases.

PMID- 11833971
TI  - Cultural meanings of tuberculosis in Aceh Province, Sumatra.
AB  - This paper shows how disease transmission and particularly what biomedicine calls
      tuberculosis are interpreted in the non-Western context of Aceh Province,
      Sumatra, Indonesia. It tries also to focus on factors influencing perceptions and
      health-seeking behaviors. Results show that what biomedicine calls TB is
      represented by a semantic network of illnesses. Parts of this network are clearly
      identified as transmissible while others are related to specific phenomena
      affecting the individual, such as terbuk (poisoning) or trouk (fatigue produced
      by hard work), and are not considered contagious. Forms of transmission are
      interpreted mostly through empirical and analogic categories. TB is attributed to
      four different aspects: (a) biomedical categories such as germ theory; (b) socio
      economic conditions; (c) transgression of social rules; and (d) poisoning and the
      influences of supernatural powers. Health-seeking behaviors are related to the
      perceived causes of the disease, economic factors, and the accessibility of
      health services.

PMID- 11833972
TI  - From childbearers to culture-bearers: transition to postchildbearing among Tuareg
      women.
AB  - This essay presents an analysis of women's lived experience of the transition
      from childbearing to postchildbearing among a division of the Tuareg in Niger,
      West Africa. The analysis suggests that biological realities associated with the
      end of fertility are interwined with local notions of qualities of ritual and
      social elderhood among women. It shows how changes in ritual and social roles,
      associated with increasing devotion to Islam and becoming a mother-in-law, are
      salient criteria for assuming the role and status of post-menopausal woman. The
      implication of this is very significant for biocultural reasons: menstruation and
      its cessation are not always literally the most important markers in female
      aging, in cross-cultural perspective.

PMID- 11833973
TI  - Inhalation toxicology of urban ambient particulate matter: acute cardiovascular
      effects in rats.
AB  - Wistar rats were exposed for 4 hours by nose-only inhalation to clean air,
      resuspended Ottawa ambient particles (EHC-93*, 48 mg/m3), the water-leached
      particles (EHC-93L, 49 mg/m3), diesel soot (5 mg/m3), or carbon black (5 mg/m3).
      Continuous data for physiologic endpoints (heart rate, blood pressure, body
      temperature, animal's activity) were captured by telemetry before and after
      exposure. Blood was sampled from jugular cannulas 1 to 3 days before exposure and
      at 2 and 24 hours after exposure, and by heart puncture on termination at 32
      hours (histology group) or 48 hours (telemetry group) after exposure. Lung injury
      was assessed by 3H-thymidine autoradiography after the rats were killed. We
      measured endothelins (plasma ET-1, big ET-1, ET-2, ET-3) to assess the
      vasopressor components; nitric oxide (NO)-related metabolites (blood nitrate,
      nitrite, nitrosyl compounds, and plasma 3-nitrotyrosine) to assess the
      vasodilator components; and catecholamines (epinephrine, norepinephrine, L-DOPA,
      dopamine) and oxidative stressors (m- and o-tyrosine) for additional insight into
      possible stress components. Lung cell labeling was uniformly low in all treatment
      groups, which indicates an absence of acute lung injury. Inhalation of EHC-93
      caused statistically significant elevations (P < 0.05) of blood pressure on day 2
      after exposure, plasma ET-1 at 32 hours after exposure, and ET-3 at 2, 32, and 48
      hours after exposure. In contrast, the modified EHC-93L particles, from which
      soluble components had been extracted, did not affect blood pressure. The EHC-93L
      particles caused early elevation (P < 0.05) of the plasma levels of ET-1, ET-2,
      and ET-3 at 2 hours after exposure, but the endothelins returned to basal levels
      32 hours after exposure. Exposure to diesel soot, but not carbon black, caused an
      elevation (P < 0.05) of plasma ET-3 at 36 hours after exposure; blood pressure
      was not affected by diesel soot. Our results indicate that inhalation of the
      urban particles EHC-93 can affect blood levels of ET-1 and ET-3 and cause a
      vasopressor response in Wistar rats without causing acute lung injury.
      Furthermore, the potency of the particles to influence hemodynamic changes
      appears to be modified by removing polar organic compounds and soluble elements.
      Because the pathophysiologic significance of elevated endothelins has been
      clinically established in humans, our observations suggest a novel mechanism by
      which inhaled particles may cause cardiovascular effects. These findings in rats
      contribute to the weight of evidence in favor of a biologically plausible
      epidemiologic association between ambient particulate matter and cardiovascular
      morbidity and mortality in human populations.

PMID- 11833974
TI  - Social support networks of lesbian, gay, and bisexual adults 60 years of age and
      older.
AB  - The social support networks of 416 lesbian, gay, and bisexual adults aged 60 to
      91 years were examined. Participants averaged 6 people in their support networks,
      most of whom were close friends. The gender composition of support networks was
      greatly influenced by the gender of the respondent. Most support network members
      knew about respondents' sexual orientation. The most common type of support
      provided by close friends and social acquaintances was socializing support, and
      the most common support provided by partners, siblings, and other relatives was
      emotional support. The sexual orientation, gender, and age of network members did
      not influence respondents' satisfaction with the support received. Participants
      were more satisfied with support from those who knew of their sexual orientation.
      The more satisfied respondents felt with the support they received, the less
      lonely they felt. Those living with domestic partners were less lonely and rated
      their physical and mental health more positively than those who lived alone.

PMID- 11833975
TI  - Age-related differences in the use of contextual information in recognition
      memory: a global matching approach.
AB  - Age differences in the processing of contextual information were investigated
      using the Item, associated Context, and Ensemble (ICE) model (K. Murnane, M. P.
      Phelps, & K. Malmberg, 1999), a general global matching model of recognition
      memory. In two experiments, young and older adults studied words in environmental
      contexts and were tested in both the same and different contexts. Patterns of
      context effects for hit rate, false alarm rate, and d' suggest that older adults
      process associated context, but have difficulties integrating items and context
      into an ensemble. Thus, older adults appear to have a specific, rather than a
      general, deficit in processing contextual information. A deficiency in ensemble
      processing may be responsible for the prevalent finding that older adults show
      poorer recognition memory performance than young adults.

PMID- 11833976
TI  - A sociocultural stress and coping model for mental health outcomes among African
      American caregivers in Southern California.
AB  - A sociocultural stress and coping model to explain emotional distress among
      caregivers of family members who have dementia across ethnic and cultural groups
      is presented and explored in a sample of 41 African American and 128 non-African
      American caregivers. In this sample, African American caregivers reported lower
      levels of burden but equal levels of depression and anxiety. In the structural
      equation model, previous reports that African Americans' lower appraisal of
      caregiving as burdensome resulted in lower levels of emotional distress were
      confirmed. However, in this model, this pathway was counterbalanced by a tendency
      of African American caregivers to use emotion-focused coping and, therefore,
      increase emotional distress. African American caregivers were also younger and in
      poorer health, factors which tend to increase both burden and emotional distress
      outcomes. As suggested by the sociocultural stress and coping model, the
      influences of ethnic group variables on stress and coping processes are complex
      and multidirectional.

PMID- 11833977
TI  - The effect of aging on adaptive eye-hand coordination.
AB  - Perceptual-motor adaptability of older adults (65 and older) was assessed.
      Participants in two groups (younger, 20-36 years, and older, 67-87 years) pointed
      100 times at a straight-ahead visual target while looking through laterally
      displacing prisms, with the hand visible early in the pointing movement.
      Aftereffect tests were administered after adaptation. Each group was then split
      into decay and readaptation subgroups in which respective treatments were given
      twice. After each treatment, aftereffect tests were readministered. Eye-hand
      total shift was significantly smaller for older participants, proprioceptive
      shift was not statistically smaller for older participants, and visual shift did
      not appear. Readaptation produced greater reduction in aftereffects than did
      decay; this effect was the same for both groups. The main conclusion is that
      perceptual-motor adaptability declines with advancing age.

PMID- 11833978
TI  - Lay person-based screening for early detection of Alzheimer's disease:
      development and validation of an instrument.
AB  - Symptoms of cognitive impairment reported to telephone interviewers by caregivers
      of 272 patients were analyzed with respect to research diagnoses of dementia. All
      patients received neuropsychological evaluation for establishing the research
      diagnoses. A data mining program that used machine learning algorithms produced
      an optimized binary decision tree for differentiating patient groups according to
      all available information. The results of this analysis were used to help four
      dementia experts create a dementia screening instrument amenable to application
      and scoring by nonclinical personnel. The validity of the resulting instrument
      was then evaluated in an independent sample of 103 patients administered
      neuropsychological testing within the previous 60 days. The psychometric
      properties of the empirically derived scale and its performance for
      discriminating control from probable or possible Alzheimer's patients indicate
      strong potential for use as a dementia screener for the general population.

PMID- 11833979
TI  - Agitated behavior in elderly nursing home residents with dementia in Japan.
AB  - This study is the first investigation of the frequency of agitated behaviors in
      elderly dementia patients in Japanese nursing homes using the Cohen-Mansfield
      Agitation Inventory (J. Cohen-Mansfield, 1991). Despite major differences between
      Japanese and American cultures, findings were highly consistent with those of
      previous U.S. studies. Physically aggressive behavior, although evidenced by only
      10-20% of the sample, comprised the strongest factor. A separate factor for
      verbal agitation also emerged. The behaviors declined during the evening and
      night shifts. In both the Japanese and U.S. samples, wandering, general
      restlessness, verbal agitation such as repetitious questioning, cursing, and
      complaining occurred most frequently. Another 4-point scale was used to code the
      degree to which agitated behavior occurred during eating, dressing, bathing, and
      toileting for each resident. The majority of aggressive behavior occurred in
      relation to personal caregiving, especially in regard to bathing. Despite major
      cultural differences, Japanese findings paralleled previous U.S. results.

PMID- 11833980
TI  - Does age change the distribution of visual attention? A comment on McCalley,
      Bouwhuis, and Juola (1995).
AB  - A paper by McCalley, Bouwhuis, and Juola (1995) suggested differences between
      younger and older adults in the use of visual cues. Furthermore, they reported
      these differences could largely be attributed to diminished (peripheral) visual
      processing capacities of elderly adults. Here, we reanalyze the data of McCalley
      and colleagues emphasizing relative rather than absolute differences. We find
      that when doing so, the data do not reveal differences in the way older and
      younger adults transiently allocate attention during visual search. Contrary to
      the conclusions of McCalley and colleagues, the similarity between the younger
      and older observers is therefore independent of the characteristics of the visual
      information. Furthermore, in our view the data suggest that older adults have
      foveal rather than peripheral visual processing difficulties. The results
      reemphasize the importance of the analytical approach taken in aging research. We
      discuss the difficulties and relevance of controlling and separating visual and
      attentional factors in age-related studies.

PMID- 11833981
TI  - Health effects of involuntary job loss among older workers: findings from the
      health and retirement survey.
AB  - OBJECTIVES: To estimate the health consequences of involuntary job loss among
      older workers in the United States. METHODS: Using longitudinal data from the
      1992 and 1994 waves of the Health and Retirement Survey, multivariate regression
      models were estimated to assess the impact of involuntary job loss on both
      physical functioning and mental health. Our analysis sample included 209 workers
      who experienced involuntary job loss between survey dates and a comparison group
      of 2,907 continuously employed workers. RESULTS: The effects of late-life
      involuntary job loss on both follow-up physical functioning and mental health
      were negative and statistically significant (p < .05), even after baseline health
      status and sociodemographic factors were controlled for. Among displaced workers,
      reemployment was positively associated with both follow-up physical functioning
      and mental health, whereas the duration of joblessness was not significantly
      associated with either outcome. DISCUSSION: The findings provide evidence of a
      causal relationship between job loss and morbidity among older workers. This
      relationship is reflected in both poorer physical functioning and mental health
      for workers who experience involuntary job loss. In addition to the economic
      consequences of worker displacement, there may be important health consequences
      of job loss, especially among older workers.

PMID- 11833982
TI  - Older men and older women in the arms of criminal law: offending patterns and
      sentencing outcomes.
AB  - OBJECTIVES: This study examines whether older defendants receive more lenient
      sentences compared with their younger counterparts and whether the effects of
      aging on sentencing outcomes manifests itself similarly across male and female
      offenders. METHODS: Using statewide data from Pennsylvania for 1990-94, logit
      models were used to assess the effects of aging on the in/out or incarcerative
      decision, and, ordinary least squares models were used to assess the effects on
      the length-of-term decision. RESULTS: Results show that older offenders of both
      genders were sentenced less harshly-they are less likely to be imprisoned than
      their younger counterparts and, if imprisoned, elderly defendants receive shorter
      prison terms. However, the elderly advantage was diminished in the case of drug
      offending, and the within-gender elderly advantage was found to be greater for
      males than for women. DISCUSSION: While these age differences in sentence
      outcomes appear to thwart norms of judicial impartiality, they also might reflect
      legitimate sentencing concerns of judges (in areas such as crime propensity,
      blameworthiness, and even the extra costs needed tojail older defendants).
      Therefore, an overall pattern of less severe punishment of older defendants
      (and/or female defendants) may still be warranted.

PMID- 11833983
TI  - The transition from home to nursing home mortality among people with dementia.
AB  - OBJECTIVES: This article examines the impact of nursing home admission on
      mortality among persons with dementia, comparing social selection and social
      causation explanations of excess deaths occurring immediately after relocation.
      METHODS: Data from a multiwave panel survey of caregivers to persons with
      Alzheimer's Disease (N = 555) are analyzed with proportional hazard models of
      time from illness onset to death of the care recipient and, for those admitted to
      a nursing home (N = 272), time from admission until death (N = 272). RESULTS:
      Relocation is associated with a two-fold increase in mortality risk net of health
      status. Social selection effects were found for poor health, advanced age, being
      male, and being White. Patients admitted for reasons other than poor health also
      experienced elevated mortality immediately following admission, which is
      inconsistent with a social selection interpretation. However, none of the
      specific indicators of stressful admission or unsatisfactory nursing home
      conditions are significantly related to mortality. DISCUSSION: These data
      demonstrate selection processes for postadmission mortality, but indicate that
      the admission of patients in poor health may not fully account for the elevation
      in mortality that occurs immediately following admission.

PMID- 11833985
TI  - Measuring morbidity: disease counts, binary variables, and statistical power.
AB  - OBJECTIVES: This study compares the use of the binary disease variables with
      counts of the same conditions in models of self-rated health to better understand
      the advantages and disadvantages of each approach. In particular, the analysis
      seeks to determine if statistical power is adequate for the binary variable
      approach. METHODS: Morbidity measures from adults in 2 large national surveys
      were used in both cross-sectional and longitudinal analyses. RESULTS: Although
      differences across the approaches are modest, the binary variable approach offers
      greater explanatory power and slightly higher R2 values. Despite these
      advantages, statistical power is insufficient in some cases, especially for
      conditions that are relatively rare and/or that manifest modest differences on
      the outcome variable. DISCUSSION: Statistical power estimates are advisable when
      using the binary variable approach, especially if the list of diseases and health
      conditions is extensive. Although a simple count of diseases may be useful in
      some research applications, separate counts for serious and nonserious conditions
      should be more useful in many research projects while avoiding the risk of
      inadequate statistical power.

PMID- 11833984
TI  - Social support for spouse caregivers of persons with dementia.
AB  - OBJECTIVES: This study analyzes the value of simultaneously taking helper and
      caregiver characteristics into account when examining social support received by
      spouse caregivers of persons with dementia. This study questions whether sources
      and types of received support vary by the gender and relationship of the helper
      and/or by the caregiver's race and gender. METHODS: Drawing on a sample of 210
      spouse caregivers of persons with dementia, the Generalized Estimating Equation
      (GEE) method was used to estimate a population-average logistic regression model
      to address cross-level helper and caregiver interactions. RESULTS: Results
      indicate that helper and caregiver characteristics interact in complex ways.
      White male caregivers are more likely to receive emotional support from adult
      children and to receive practical assistance from formal sources compared with
      other types of support and to other race-gender caregiver groups. DISCUSSION:
      Description of social status characteristics of caregivers as determinants of
      their social network may be less fruitful in understanding the benefits of social
      support than a focus on which helpers assist with what kinds of task for which
      groups of caregivers.

PMID- 11833986
TI  - Functional status and hearing impairments in women at midlife.
AB  - OBJECTIVES: The aim of this study was to address the prevalence of clinically
      assessed high-frequency hearing impairment (HFHI) and self-reported hearing
      impairment (SRHI) and examine the association of these hearing assessments with
      physical and mental functioning in African American and Caucasian women at
      midlife. METHODS: The sample included 467 women who participated in the Michigan
      Functioning Substudy of the Study of Women's Health Across the Nation. Outcomes
      examined were physical and mental functioning from the Medical Outcomes Trust SF
      12 Health Survey. HFHI was defined as threshold averages of 25 dB or greater over
      4000, 6000, and 8000 Hertz. RESULTS: Prevalence of unilateral HFHI was 26.6% (n =
      68), and prevalence of bilateral HFHI was 12.0% (n = 56). Prevalence of SRHI was
      16.7% (n = 78), with minimal overlap between HFHI and SRHI (n = 36). In multiple
      variable logistic regression analyses, HFHI in one ear only was not associated
      with physical or mental functioning and bilateral HFHI was associated with
      limited mental functioning only. SRHI was associated with limited physical and
      mental functioning. DISCUSSION: Poor correlation of HFHI and SRHI in this
      population, combined with the significant association of SRHI with both measures
      of functioning, indicates that the two methods may be measuring different aspects
      of impairment. SRHI may facilitate early identification of individuals with
      hearing-related functional limitations.

PMID- 11833987
TI  - Jitter produces rollover.

PMID- 11833988
TI  - Asymmetry in event-related potentials to simulated auditory motion in children,
      young adults, and seniors.
AB  - We studied auditory evoked responses to the apparent movement of a burst of noise
      in the horizontal plane. Event-related potentials (ERPs) were measured in three
      groups of participants: children in the age range from 9 to 12 years, young
      adults in the age range from 18 to 34 years, and seniors in the age range from 65
      to 80 years. The topographic distribution of grand-averaged ERP activity was
      substantially greater over the right hemisphere in children and seniors but
      slightly greater over the left hemisphere in young adults. This finding may be
      related to age-related differences in the extent to which judgments of sound
      movement are based on displacement versus velocity information.

PMID- 11833989
TI  - Benefits of syllabic input compression for users of cochlear implants.
AB  - Ten users of multielectrode cochlear implants participated in an evaluation of
      the perceptual effects of input-signal compression. A syllabic compressor was
      introduced into the microphone circuit of Spectra-22 or SPrint sound processors.
      The post-compression gain was adjusted to provide similar loudness for speech at
      an average level of 65 dBA with compression either enabled or disabled. Sentence
      recognition was measured at three levels. Averaged across all listeners,
      statistically significant score increases were obtained at each level with
      compression enabled (45 dBA: 19.6 percentage points, p < .0001; 55 dBA: 16.6
      percentage points, p < .0001; 70 dBA: 3.1 percentage points, p = .031). A test of
      speech intelligibility in noise showed no significant effect of compression.
      Generally, participants in the trial reported improved perception of low-level
      sounds with compression, although a few disliked the increased loudness of some
      background noises. Some participants suggested that the ability to enable or
      disable compression with a manual switch would be helpful. Overall, the results
      show that input compression can improve the performance of these sound processors
      for users of cochlear implants, especially when listening to speech at low
      levels.

PMID- 11833990
TI  - Observations on the relations among occlusion effect, compliance, and vent size.
AB  - In a clinical experiment, it was found that there is a high correlation between
      the compliance measured by tympanometry and the minimum size of the earmold vent,
      which just solves the client's occlusion problem related to his/her own voice
      when using a hearing aid. For ears with sensorineural hearing losses, compliance
      explained 59 percent of the variation in vent size, whereas the average low
      frequency hearing loss explained as little as 0.3 percent. In a laboratory
      experiment, the objective occlusion effect measured with the participants' own
      voices showed a similar relationship with compliance. Whereas the former
      relationship between compliance and vent size may be explained by a simple model,
      the latter relationship turns out to be the opposite of what a first-order model
      predicts. Hence, compliance must be indicative of another aspect of the occlusion
      mechanism, which has a more profound influence on the observed occlusion effect
      than compliance itself.

PMID- 11833991
TI  - A test to measure subjective and objective speech intelligibility.
AB  - Measurement of hearing aid outcome is particularly difficult because there are
      numerous dimensions to consider (e.g., performance, satisfaction, benefit). Often
      there are discrepancies between scores in these dimensions. It is difficult to
      reconcile these discrepancies because the materials and formats used to measure
      each dimension are so very different. We report data obtained with an outcome
      measure that examines both objective and subjective dimensions with the same test
      format and materials and gives results in the same unit of measurement (signal-to
      noise ratio). Two variables are measured: a "performance" speech reception
      threshold and a "perceptual" speech reception threshold. The signal-to-noise
      ratio difference between these is computed to determine the perceptual
      performance discrepancy (PPDIS). The results showed that, on average, 48 percent
      of the variance in subjective ratings of a hearing aid could be explained by a
      combination of the performance speech reception threshold and the PPDIS. These
      findings suggest that the measure is potentially a valuable clinical tool.

PMID- 11833992
TI  - Temporally jittered speech produces performance intensity, phonetically balanced
      rollover in young normal-hearing listeners.
AB  - This study investigates whether temporally jittered stimuli will produce
      performance-intensity, phonetically balanced (PI-PB) rollover in young adults
      with normal hearing. Although not yet explicitly stated in the literature, there
      is clinical and theoretical evidence to suggest that PI-PB rollover, such as that
      found in cases of acoustic neuroma, is caused by neural dyssynchrony in the
      auditory system. Sixteen participants were tested with intact and temporally
      jittered word lists in quiet at 40, 55, 65, and uncomfortable listening level -5
      dB HL. The results show significant rollover in the jittered but not the intact
      conditions. The results are consistent with the existing evidence that suggests
      that neural PI-PB rollover is caused by decreased neural synchrony and support
      the claim that temporal jitter simulates neural dyssynchrony. Furthermore, these
      results are consistent with the hypothesis that synchrony coding plays an
      important role in the perception of high-level speech.

PMID- 11833993
TI  - Arrhythmia after modified total cavopulmonary connection without use of
      prosthetic material.
AB  - BACKGROUND: Although total cavopulmonary connection without use of prosthetic
      material appeared to be a promising surgical procedure that would retain
      potential growth of the intraatrial tunnel, midterm incidence of arrhythmia
      remains unknown. METHODS: Twelve patients underwent modified total cavopulmonary
      connection. A prosthetic material was not used in 5 patients (group F) and was
      used in 7 patients (group P). A retrospective review of the perioperative
      electrocardiogram and ambulatory monitoring were performed. RESULTS: All patients
      revealed regular sinus rhythm before the operation. In the early postoperative
      period, the incidence of sinus node dysfunction was higher in group F than in
      group P (80% versus 28.6%). This difference no longer existed by hospital
      discharge (group F, 20%; group P, 14.3%). In the midterm follow-up period, sinus
      node dysfunction was detected in 4 patients of group F (80%) and 1 patient of
      group P (14.3%). Transient tachyarrhythmia was detected in 1 patient of group F
      and 3 patients of group P. CONCLUSIONS: Modified total cavopulmonary connection
      without use of prosthetic material affected unfavorably the sinus node in the
      early and midterm postoperative period.

PMID- 11833994
TI  - Atrial size and transport function after the Maze III procedure for paroxysmal
      atrial fibrillation.
AB  - BACKGROUND: The Maze procedure is a curative surgical therapy for atrial
      fibrillation, restoring sinus rhythm and improving quality of life. Because the
      procedure results in tissue scarring, the atrial transport function is most
      likely affected. METHODS: Seventeen patients with paroxysmal atrial fibrillation
      underwent the Maze III procedure without any concomitant valve operation. Atrial
      size and transport function were measured before and at 2, 6, and 24 months after
      operations with two-dimensional echocardiography and pulsed-wave Doppler.
      RESULTS: Fifteen patients (88%) had signs of left atrial contractions as shown by
      the presence of a transmitral atrial filling wave on Doppler echocardiography at
      6 months follow-up. The transmitral early filling wave and atrial filling wave
      were measured to calculate the early filling/atrial filling wave ratio, which
      increased from 1.2 before to 1.9 at 2 months after the Maze procedure
      (nonsignificant), and further to 2.8 at 24 months (p = 0.02). A decrease in the
      right and left atrial size was seen at 2 months after an operation, but no
      further decrease occurred. CONCLUSIONS: In patients with paroxysmal atrial
      fibrillation, there is a progressive increase in the transmitral early
      filling/atrial filling wave ratio after the Maze procedure, consistent with a
      gradual decrease in the left atrial transport function.

PMID- 11833995
TI  - A passion to heal.

PMID- 11833997
TI  - Injury of the common peroneal nerve after cardiothoracic operations.
AB  - BACKGROUND: To assess incidence, etiology, and clinical relevance of common
      peroneal nerve injury (CPNI) in patients after cardiothoracic surgery. METHODS:
      In an 11-year period, CPNI was detected in 39 out of 20,718 patients (0.19%): 38
      times after cardiopulmonary bypass (CPB) (38 of 12,726; 0.30%) and in 1 patient
      after a non-CPB procedure (1 of 7,992; 0.013%). These patients underwent
      intensive physiotherapeutic treatment. As the majority of CPNI occurred after CPB
      (97.4%), data of these patients were compared with a 1-year set of 1,032 patients
      who underwent CPB procedures. RESULTS: Patients with CPNI were older, had a
      higher percentage of subnormal body weight, and had considerable comorbidity such
      as peripheral arteriosclerotic disease, diabetes mellitus, and arrhythmias.
      Follow-up was complete (mean: 5.2 years; 0.4 to 10.7 years). Twenty-eight
      patients were free of symptoms; 10 patients complained of moderate symptoms, but
      were not limited in their everyday life; 1 patient still suffers from severe
      sensorimotor symptoms. CONCLUSIONS: CPNI after cardiothoracic surgery is rare.
      Duration of the operative procedure, an increased comorbidity, and a subnormal
      body weight are assumed to have an etiologic impact. Prognosis is mostly good,
      but early physiotherapeutic treatment is crucial for prognosis.

PMID- 11833996
TI  - Magnesium-supplemented warm blood cardioplegia in patients undergoing coronary
      artery revascularization.
AB  - BACKGROUND: Although there is growing evidence to suggest that the administration
      of magnesium (Mg2+) to patients undergoing coronary artery bypass grafting (CABG)
      and to patients after myocardial infarction is beneficial, the addition of Mg2+
      to cardioplegic solutions remains controversial. The aim of this study was to
      compare the effects of intermittent warm blood cardioplegia with and without Mg2+
      supplementation on the early postoperative clinical outcomes in patients
      undergoing both elective or urgent CABG. METHODS: Four hundred patients
      undergoing CABG were prospectively randomized to receive either blood
      cardioplegia without Mg2+ (BC, n = 200) or supplemented with Mg2+ (BC-Mg2+, n =
      200). Serial plasma Mg2+ concentrations were recorded at base line and
      postoperatively from days 1 to 4. RESULTS: Patient characteristics were similar
      and no significant differences were found in early mortality and morbidity in the
      two groups. Analysis of 178 patients undergoing urgent CABG for unstable symptoms
      (BC = 95, BC-Mg2+ = 83) demonstrated a significantly lower requirement for
      internal defibrillation and temporary epicardial pacing in the BC-Mg2+ group.
      Furthermore, there was a nearly twofold lower incidence of new postoperative
      atrial fibrillation in the BC-Mg2+ group compared with the BC group (19% versus
      34%, p = 0.03). Postoperative plasma Mg2+ levels were consistently lower in those
      patients who developed new postoperative atrial fibrillation compared with those
      who did not (p = 0.05). CONCLUSIONS: The addition of Mg2+ to warm blood
      cardioplegia resulted in a lower incidence of intraoperative and postoperative
      arrhythmias in patients undergoing urgent CABG for unstable angina.

PMID- 11833998
TI  - Inhibition of neutrophil apoptosis after coronary bypass operation with
      cardiopulmonary bypass.
AB  - BACKGROUND: Granulocyte apoptosis is a key control process in the clearance of
      neutrophils from inflammatory sites, and its rate is modulated both in vitro and
      in vivo by a number of inflammatory mediators. In this study, we investigated the
      influence of cardiopulmonary bypass (CPB) on neutrophil apoptosis. METHODS:
      Twenty patients undergoing coronary operation with CPB were studied. Patients
      undergoing off-pump (OP) coronary bypass and healthy subjects served respectively
      as stressed and normal groups. Interleukin-6 (IL-6), IL-8, and tumor necrosis
      factor-alpha were assessed on plasma collected preoperatively, at the end of CPB,
      and after intervals of 4, 8, 12, and 24 hours. Neutrophil apoptosis was detected
      by light microscopy as well as by the annexin-V assay on postoperative samples.
      The polymorphonuclear leukocyte (PMN) apoptotic receptors, Fas and FasL, were
      studied together with the activity of caspase 3 in postoperative neutrophils.
      RESULTS: Spontaneous apoptosis was significantly delayed in PMNs from CPB
      patients when compared with either the stressed or control patients. Neutrophils
      were activated, as indicated by increased surface expression of CD11b. Western
      blot analysis showed a normal expression of the apoptotic receptors Fas and FasL.
      Caspase 3 activity was found to be significantly reduced in neutrophils from CPB
      patients after 18 and 24 hours of culture. When control neutrophils were cultured
      in the presence of postoperative plasma from OP and CPB patients, apoptosis was
      significantly delayed. Depleting surgical plasma of IL-6 and IL-8 completely
      abolished this antiapoptotic effect. CONCLUSIONS: Inflammatory mediators during
      CPB prolong the functional lifespan of neutrophils through modulation of
      apoptosis, and potentiate the inflammatory response observed after coronary
      bypass operation.

PMID- 11833999
TI  - Flow dynamics in internal thoracic artery grafts 10 years after coronary artery
      bypass grafting.
AB  - BACKGROUND: Flow dynamics in internal thoracic artery grafts 10 years after
      surgery are not known. METHODS: Doppler examination was performed in native
      internal thoracic arteries as a control (n = 8) and in internal thoracic artery
      grafts to the left anterior descending coronary artery 6 months postoperatively
      (group A, n = 25), at 5 years (group B, n = 14), and at 10 years (group C, n =
      11). RESULTS: Each graft group showed a diastolic to systolic peak velocity ratio
      of less than 1.0 at the proximal end, and more than 1.0 at the distal end, but
      the control group showed a ratio of less than 1.0 throughout the length of the
      artery. The diastolic peak velocity of the graft groups was significantly faster
      than that of the control group at the distal end (versus group A, p < 0.01;
      versus group B, p < 0.005; and versus group C, p < 0.05). The systolic peak
      velocity of the graft groups was significantly lower than that of the control at
      the proximal end (versus group A, p < 0.0001; versus group B, p < 0.005; and
      versus group C, p < 0.0005). There were no significant differences of flow
      velocities among the graft groups and graft diameter among the four groups.
      CONCLUSIONS: Although the internal thoracic artery is systolic predominant, when
      native artery is used as graft, it changes its hemodynamics to diastolic
      predominance, especially at the distal end. Even after 10 years, graft flow
      dynamics are unchanged. This hemodynamic character may be one of the factors
      related to the superior long-term patency.

PMID- 11834000
TI  - Association of bacterial infection and red blood cell transfusion after coronary
      artery bypass surgery.
AB  - BACKGROUND: Previous studies have shown an association between red blood cell
      transfusions (RBC) and bacterial infections following coronary artery bypass
      graft (CABG) surgery. We sought to assess whether there is an independent effect
      of RBC on the incidence of bacterial infections. METHODS: This was a prospective
      cohort study of 533 CABG patients over a 7-month period. Subjects were followed
      from time of CABG until 30 days postoperatively. Data were collected on patient
      and treatment characteristics, surgical management, and transfusion incidence.
      RESULTS: Seventy-five (14.1%) of 533 patients developed a bacterial infection.
      After controlling for patient and disease characteristics, invasive treatments,
      surgical time, and the transfusion of other substances, the adjusted rates of
      bacterial infection were 4.8% for no RBC transfusion, 15.2% with one to two
      units, 22.1% with three to five units, and 29.0% with greater than or equal to
      six units, (p(trend) < 0.001). Diabetes was the only patient or disease factor
      significantly associated with bacterial infection (p < 0.001). CONCLUSIONS: RBC
      transfusions were independently associated with a higher incidence of post-CABG
      bacterial infections. The risk of infection increased in proportion to the number
      of units of RBC transfused.

PMID- 11834001
TI  - The radial artery in coronary surgery: a 5-year experience--clinical and
      angiographic results.
AB  - BACKGROUND: The radial artery (RA) has been used extensively by us as a way of
      reducing the use of the saphenous vein. It has been hoped that the RA will
      maintain greater late patency than the saphenous vein. We evaluated our initial 5
      year experience with the RA in coronary surgery. METHODS: We studied 6,646
      consecutive patients who had a single RA (4,872), or bilateral RA (1,774), as
      coronary grafts, from June 1995 to June 2000. Angiograms were performed mostly in
      symptomatic patients, or as part of a research project in asymptomatic patients.
      RESULTS: The patients' mean age was 65.1 years; 23% had diabetes, 14% had
      unstable angina, and 42% had prior myocardial infarction. An average of 3.3
      grafts per patient were performed, 87% from arterial conduit. Conduits used were
      RA (8,420), left internal thoracic artery (6,296), and right internal thoracic
      artery (1,076). Operative mortality occurred in 58 (0.9%) patients, stroke in 92
      (1.4%), deep sternal infection in 97 (1.4%), reoperation for hemorrhage in 56
      (0.9%), and myocardial infarction in 52 (0.8%). Peak mean postoperative creatine
      kinase MB (CKMB) was 16.5 IU/L. Two patients developed fingertip ischemia.
      Postoperative angiographic RA patency was 90.2% (333 of 369 distal anastomoses).
      CONCLUSIONS: Good early clinical and angiographic results can be achieved by
      using the RA in coronary surgery.

PMID- 11834002
TI  - Left pleural effusion after coronary artery bypass decreases with a supplemental
      pleural drain.
AB  - BACKGROUND: This prospective study was undertaken to determine the incidence of
      symptomatic left pleural effusion after coronary artery bypass grafting, and to
      determine if routine drainage of the pleural cavity with a supplemental flexible
      drain reduces this incidence. METHODS: The clinical course of study patients was
      prospectively recorded during the initial hospitalization and at 6-weeks after
      surgery. All patients had a mediastinal and a left pleural tube, which were
      removed on the 1st postoperative day. The supplemental drain system was implanted
      in a subset of patients and remained in place for 3 to 5 days. A symptomatic
      effusion was defined as one that required thoracentesis, tube thoracostomy, or
      readmission for treatment. RESULTS: A total of 460 patients were studied, of whom
      115 had a supplemental drain. The two groups (supplemental drain versus control)
      were equivalent with respect to age, gender distribution, and comorbid diseases.
      The incidence of symptomatic left pleural effusion for the entire group was 9.8%
      (45 of 460). Symptomatic left pleural effusion occurred in 11.9% (41 of 345)
      patients when only chest tubes were used, and in 3.5% (4 of 115) when a
      supplemental drain was placed. This difference was significant (F ratio 7.583, p
      < 0.005). There were no complications from the supplemental drain. CONCLUSIONS:
      The incidence of symptomatic left pleural effusion can be greatly reduced with
      the use of a supplemental pleural drain that remains in place for several days
      after surgery.

PMID- 11834003
TI  - Writing in a borrowed tongue.

PMID- 11834004
TI  - Evaluating routine diuretics after coronary surgery: a prospective randomized
      controlled trial.
AB  - BACKGROUND: Routine diuretic administration after cardiopulmonary bypass is
      common despite the lack of evidence for its benefit. We performed a prospective
      study to evaluate if diuretics assist in weight loss or alter clinical outcome.
      METHODS: Seventy-nine patients undergoing primary elective coronary bypass
      surgery were randomized to either diuretic (fusemide and amiloride) or placebo
      (lactose) postoperatively until preoperative weight was achieved or for 5 days in
      total. Proportions were compared with chi2 or Fisher's exact test. RESULTS: Forty
      patients were randomized to diuretics and 39 to placebo. By day 5, 97% of
      patients (37 of 38) still in the diuretic arm, and 74% of patients (29 of 39) in
      the placebo arm, achieved preoperative weight (p = 0.02). There were no
      differences in clinical outcomes. CONCLUSIONS: Routine diuretics promote an
      earlier diuresis but no clinical benefits are apparent in low risk patients with
      normal renal function. Clinicians should reconsider routine diuretic prescription
      in this setting.

PMID- 11834005
TI  - Myocardial immediate early gene activation after cardiopulmonary bypass with
      cardiac ischemia-reperfusion.
AB  - BACKGROUND: The inflammatory process after cardiopulmonary bypass is accompanied
      by alterations in gene expression for various inflammatory mediators. METHODS: To
      analyze differential gene expression after myocardial ischemia-reperfusion,
      subtraction hybridization was used to discover induction of TIS7/PC4, an
      immediate early gene heretofore not observed in the heart. This prompted
      characterization of the related immediate early genes c-fos and c-jun, by
      Northern analysis and in situ hybridization in human and lamb myocardium
      subjected to cardiopulmonary bypass with myocardial ischemia. For comparison, we
      analyzed expression of inducible nitric oxide synthase (iNOS), which requires
      cytokine-activation, resulting in a "delayed" response. RESULTS: In ischemic
      reperfused myocardium at endcardiopulmonary bypass, c-fos, c-jun, and TIS7/PC4
      were induced, whereas iNOS transcripts were undetectable. Expression patterns of
      c-fos and c-jun by in situ hybridization were markedly different; myocardial c
      fos expression was diffuse and homogeneous, whereas c-jun expression was patchy
      with areas of intense focal localization. CONCLUSIONS: Cardiopulmonary bypass
      with myocardial ischemia rapidly induces the immediate early genes TIS7/PC4
      (discovered by subtraction hybridization), and c-fos and c-jun (precursors to the
      transcriptional regulator AP-1). Immediate early genes presumably contribute to
      activation of inflammatory mediators after cardiopulmonary bypass and differences
      in their tissue expression patterns, as observed for c-fos and c-jun, presumably
      modulate their effect upon downstream gene activation.

PMID- 11834006
TI  - Lamotrigine plus leukocyte filtration as a neuroprotective strategy in
      experimental hypothermic circulatory arrest.
AB  - BACKGROUND: Lamotrigine and leukocyte filtration seem to improve cerebral
      protection during experimental hypothermic circulatory arrest (HCA). This study
      was performed to evaluate whether their combined use may further improve cerebral
      protection. METHODS: Twenty-four pigs undergoing 75-minute period of HCA at 20
      degrees C were randomly assigned to receive saline; lamotrigine (20 mg/kg) before
      HCA (L); or lamotrigine (20 mg/kg) before HCA plus leukocyte filtration before
      and after HCA (L + LF). RESULTS: Seven animals (87%) in the L + LF group, 4 (50%)
      in the L group, and 3 (37%) in the control group were alive on the seventh
      postoperative day. The median electroencephalogram burst recovery was 94% in the
      L + LF group (p = 0.024 versus control group), 81% in the L group, and 64% in the
      control group. Among the surviving animals, the median behavioral scores were 9,
      9, and 6 at the seventh day, respectively (p = 0.005 between the L + LF group and
      the control group). The median histopathologic score was 14 in the L + LF group
      (p = 0.046 versus control group), 14.5 in the L group (p = 0.062 versus control
      group), and 21 in the control group. CONCLUSIONS: Lamotrigine has neuroprotective
      effect during HCA. The combined use of lamotrigine and LF may further improve the
      survival outcome.

PMID- 11834007
TI  - Yearly rupture or dissection rates for thoracic aortic aneurysms: simple
      prediction based on size.
AB  - BACKGROUND: Prior work has clarified the cumulative, lifetime risk of rupture or
      dissection based on the size of thoracic aneurysms. Ability to estimate simply
      the yearly rate of rupture or dissection would greatly enhance clinical decision
      making for specific patients. Calculation of such a rate requires robust data.
      METHODS: Data on 721 patients (446 male, 275 female; median age, 65.8 years;
      range, 8 to 95 years) with thoracic aortic disease was prospectively entered into
      a computerized database over 9 years. Three thousand one hundred fifteen imaging
      studies were available on these patients. Five hundred seventy met inclusion
      criteria in terms of length of follow-up and form the basis for the survival
      analysis. Three hundred four patients were dissection-free at presentation; their
      natural history was followed for rupture, dissection, and death. Patients were
      excluded from analysis once operation occurred. RESULTS: Five-year survival in
      patients not operated on was 54% at 5 years. Ninety-two hard end points were
      realized in serial follow-up, including 55 deaths, 13 ruptures, and 24
      dissections. Aortic size was a very strong predictor of rupture, dissection, and
      mortality. For aneurysms greater than 6 cm in diameter, rupture occurred at 3.7%
      per year, rupture or dissection at 6.9% per year, death at 11.8%, and death,
      rupture, or dissection at 15.6% per year. At size greater than 6.0 cm, the odds
      ratio for rupture was increased 27-fold (p = 0.0023). The aorta grew at a mean of
      0.10 cm per year. Elective, preemptive surgical repair restored life expectancy
      to normal. CONCLUSIONS: This study indicates that (1) thoracic aneurysm is a
      lethal disease; (2) aneurysm size has a profound impact on rupture, dissection,
      and death; (3) for counseling purposes, the patient with an aneurysm exceeding 6
      cm can expect a yearly rate of rupture or dissection of at least 6.9% and a death
      rate of 11.8%; and (4) elective surgical repair restores survival to near normal.
      This analysis strongly supports careful radiologic follow-up and elective,
      preemptive surgical intervention for the otherwise lethal condition of large
      thoracic aortic aneurysm.

PMID- 11834008
TI  - Long-term treatment with nipradilol, a nitric oxide-releasing beta-adrenergic
      blocker, enhances postischemic recovery and limits infarct size.
AB  - BACKGROUND: This study examines whether the chronic administration of nipradilol,
      a nitric oxide-releasing beta-adrenergic blocker, decreases ischemia-reperfusion
      injury. METHODS: Rats were treated with nipradilol (10 mg/kg per day orally) or a
      vehicle alone for 4 weeks. Isolated rat hearts were assigned to one of five
      groups (each n = 6): global ischemia groups treated with the vehicle or with
      nipradilol were subjected to 20 minutes of ischemia; ischemic preconditioning
      groups treated with the vehicle or with nipradilol were subjected to 3 minutes of
      ischemic preconditioning; and the L-arginine group treated with the vehicle
      received 1 mmol/L of L-arginine before global ischemia. Hemodynamic variables and
      coronary flow were recorded continuously. Nitrites and nitrates levels were
      measured 60 minutes after reperfusion, and the infarct size was determined. In
      another series (each n = 6), lipid peroxidation was investigated. RESULTS: In the
      nipradilol group, significant preservation of the left ventricular pressure and
      coronary flow, as well as the level of nitrates and nitrites, was observed,
      compared with the global ischemia group. The infarct size was also significantly
      reduced in the ischemic preconditioning (23.5%+/-5.47%), L-arginine (25.6%+/
      5.59%), and especially the nipradilol (10.7%+/-1.65%) groups. However, in the
      nipradilol plus ischemic preconditioning group, the protective effects were
      eliminated. Lipid peroxidation after nipradilol treatment was significantly
      reduced before and after global ischemia, compared with the global ischemia
      group. CONCLUSIONS: The chronic administration of nipradilol improves
      postischemic functional recovery and infarct size, partly by preventing the
      formation of lipid peroxides. These cardioprotective effects were, however,
      abolished by ischemic preconditioning.

PMID- 11834010
TI  - Profound reduction in brain embolization using an endoaortic baffle during bypass
      in swine.
AB  - BACKGROUND: Cerebral embolization during cardiopulmonary bypass is an important
      cause of neurologic injury. This study determined whether an endoaortic baffle
      catheter (Cardeon Cobra Catheter; Cardeon Corporation, Cupertino, CA) could
      substantially reduce cerebral embolization in a swine cardiopulmonary bypass
      model. METHODS: Sixteen 60 kg pigs underwent cardiopulmonary bypass; 8 animals
      with the Cobra baffle (Cardeon Corporation, Cupertino, CA) deployed, and 8 with
      the same cannula without baffle deployment. The animals were embolized with
      72,000 fluorescent microspheres (97 to 100 microm) at normothermia. At the end of
      the experiment, the brains were removed and microspheres were isolated from eight
      regions. RESULTS: During embolization, the two groups were equivalent with regard
      to pump flow, mean arterial pressure, temperature, Hgb and PaCO2. Deployment of
      the Cobra baffle reduced embolization to every brain region. Deployment of the
      baffle reduced total brain embolization by 89%. There was a mean of 61+/-60
      emboli per gram in the control animals and 7+/-24 emboli per gram in those
      animals in which the baffle was deployed. CONCLUSIONS: Cerebral embolization is
      profoundly reduced by use of the Cobra baffle aortic cannula. The application of
      this device may reduce postcardiac surgical neurologic injury.

PMID- 11834009
TI  - Effect of hypothermia on cerebral blood flow and metabolism in the pig.
AB  - BACKGROUND: The pig has become an increasingly popular model for the study of
      cerebral protection during cardiothoracic surgery in recent years, but little
      information is available concerning hypothermic porcine physiology. Because the
      efficacy of cerebral protection depends largely upon metabolic suppression, we
      studied cerebral oxygen metabolism at various temperatures using two different
      methods to assess cerebral blood flow (CBF). MATERIAL AND METHODS: Twelve pigs (7
      to 13 kg) underwent cooling on cardiopulmonary bypass to 8 degrees C as recorded
      by an electrode placed deep in the parenchyma of the brain. CBF was measured in 6
      animals using radioactive microspheres and in the other 6 using fluorescent
      microspheres. CBF, cerebral oxygen consumption, and cerebral vascular resistance
      were determined at 37 degrees C, 28 degrees C, 18 degrees C, and 8 degrees C.
      RESULTS: Both methods produced very similar data. CBF fell steadily with decrease
      in temperature to 18 degrees C but failed to drop further with more profound
      hypothermia. With both groups combined, mean cerebral oxygen metabolism was 2.63
      mL/100 g per minute at 37 degrees C. Metabolic activity was 50% of base line
      values at 28 degrees C, 19% at 18 degrees C, and 11% at 8 degrees C. The Q10
      value in the pig--the degree of metabolic suppression achieved by a 10 degrees C
      drop in temperature--is 2.46 (95% confidence interval 2.1 to 2.9); this value is
      consistent with similar studies in humans. CONCLUSIONS: The presence of
      significant residual metabolic activity at 18 degrees C suggests that this degree
      of hypothermia may provide incomplete cerebral protection during prolonged
      interruption of CBF. This study demonstrates that cooling to temperatures below
      18 degrees C in the pig can achieve greater metabolic suppression although it may
      be associated with loss of cerebral autoregulation.

PMID- 11834011
TI  - Comparing dual-stream and standard cardiopulmonary bypass in pigs.
AB  - BACKGROUND: Dual-stream (DS) and standard cardiopulmonary bypass (CPB) were
      compared. METHODS: A DS catheter inserted into the distal ascending aorta across
      the arch pumps blood through an upper lumen (maximum 2.25 L/min) directed by a
      bloodstreaming baffle toward the arch vessels. A separate lower lumen pumps blood
      (maximum 3.75 L/min) into the aorta caudad to the inflated baffle. The baffle is
      flat and horizontal along the catheter. When the baffle is collapsed the heart or
      both lumens may perfuse all organs. For 30 minutes 8 randomized CPB pigs had
      corporeal cooling to 32 degrees C and for 30 minutes had rewarming to 36 degrees
      C. Eight randomized DS pigs had 25 degrees C upper lumen cooling for 60 minutes.
      Lower lumen blood flow was streamed at 32 degrees C for 30 minutes, then rewarmed
      to 36 degrees C for 30 minutes. RESULTS: The change in relative lower lumen to
      brain blood flow as determined by brain-counted microspheres (15 micron) injected
      into the ascending aorta was less for DS brains than controls during full flow
      (DS 63.4+/-129.5 versus CPB 2,585.4+/-250.8, p < 0.001), and when injected into
      the ejecting-heart left atrium just after weaning off only lower lumen blood flow
      (DS 250.8+/-297.3 versus CPB 1,159.1+/-782.3, p < 0.001). DS brain temperatures
      were lower at an equal pump-off core temperature of 36 degrees C+/-0.5 degrees C
      (DS 31.6 degrees C+/-3.2 degrees C versus CPB 36.5 degrees C+/-1.7 degrees C, p <
      0.025). Jugular O2 saturations were not different. CONCLUSIONS: DS-CPB
      prioritizes pump-filtered separate cold blood flow to the brain over a blood
      streaming baffle to wash away potentially surgery related air and particulate
      matter arising from the heart or ascending aorta.

PMID- 11834012
TI  - Lung transplantation for pulmonary vascular disease.
AB  - BACKGROUND: Pulmonary hypertension (PHT) is a lethal condition resulting in
      markedly diminished life expectancy. Continuous prostaglandin I2 infusion has
      made an important contribution to symptom management, but it is not a panacea.
      Lung or heart-lung transplantation remains an important treatment option for end
      stage PHT patients unresponsive to prostaglandin I2. This study reviews the
      outcomes after transplantation for PHT in our program. METHODS: A retrospective
      chart review was performed for 100 consecutive patients with either primary PHT
      (48%) or secondary PHT (52%) transplants since 1989. Living recipients were
      contacted to confirm health and functional status. RESULTS: Fifty-five adult and
      45 pediatric patients underwent 51 bilateral lung transplants, 39 single lung
      transplants, and 10 heart-lung transplants. Mean age was 23.7 years (range, 1.2
      months to 54.8 years) and mean pre-transplant New York Heart Association class
      was 3.2. Pre-transplant hemodynamics revealed a mean right atrial pressure of
      9.6+/-5.4 mm Hg and mean pulmonary artery pressure of 64+/-14.4 mm Hg. Hospital
      mortality was 17% with early death predominantly because of graft failure and
      infection. With an average follow-up of 5.0 years, 1- and 5-year actuarial
      survival was 75% and 57%, respectively. Mean pulmonary artery pressure on follow
      up catheterization was 22+/-6.0 mm Hg, and mean follow-up New York Heart
      Association class was 1.3 (p < 0.001 for both compared with pre-transplant).
      Diagnosis and type of transplant did not confer a significant difference in
      survival between groups. CONCLUSIONS: Whereas lung or heart-lung transplant for
      PHT is associated with higher early mortality than other pulmonary disease
      entities, it provides similar long-term outcomes with dramatic improvement in
      both quality of life and physiologic aspects.

PMID- 11834013
TI  - Melatonin attenuates posttransplant lung ischemia-reperfusion injury.
AB  - BACKGROUND: Melatonin, a pineal hormone, is a free radical scavenger and an
      antioxidant. The purpose of this study was to assess the protective effect of
      melatonin on posttransplant lung ischemia-reperfusion injury. METHODS: Rat single
      lung transplantation was performed in two (n = 10) experimental groups after 18
      hours of cold (4 degrees C) ischemia. Group I animals consisted of the ischemic
      control group. In group II, donor and recipient animals were treated with
      intraperitoneal injection of 10 mg/kg melatonin 10 minutes before harvest and
      reperfusion, respectively. After 2 hours of reperfusion, oxygenation, plasma, and
      bronchoalveolar lavage nitrite levels were measured. Lung tissue was assessed for
      thiobarbituric acid reactive substances and myeloperoxidase activity. Peak airway
      pressure was recorded throughout the reperfusion period. RESULTS: The melatonin
      treated group showed significantly better oxygenation (321.8+/-33.8 mm Hg versus
      86.1+/-17.4 mm Hg; p < 0.001), reduced lipid peroxidation (0.65+/-0.3 nmol/g
      versus 1.63+/-0.8 nmol/g; p = 0.032), and reduced myeloperoxidase activity
      (0.56+/-0.1 deltaOD x mg(-1) x min(-1) versus 1.01+/-0.2 deltaOD x mg(-1) x min(
      1); p = 0.032). Bronchoalveolar lavage nitrite levels in the transplanted lungs
      were significantly lower in group II than in group I (0.34+/-0.06 micromol/L
      versus 1.65+/-0.6 micromol/L; p = 0.016). In group II significant reduction in
      peak airway pressure was noted compared with group I (p = 0.002). CONCLUSIONS: In
      this model, exogenously administered melatonin effectively protected lungs from
      reperfusion injury after prolonged ischemia.

PMID- 11834014
TI  - Pulmonary blood flow is inhomogeneously reduced after Euro Collins-preservation
      and lung transplantation.
AB  - BACKGROUND: Vasoconstriction after lung transplantation is a well-known
      phenomenon, but only limited information is available on blood flow distribution
      after ischemia and reperfusion. The aim of our study was to determine the
      regional flow characteristics in transplanted and native dog lungs after 24 hours
      of cold storage and preservation with Euro Collins-solution. METHODS: Six pairs
      of weight-matched Foxhounds (25 to 30 kg) were used. In donors and recipients,
      aortic and pulmonary artery catheters were inserted percutaneously and a
      reference withdrawal catheter was placed into the main pulmonary artery. For
      preservation, the lungs were perfused with modified Euro Collins-solution and
      stored at 4 degrees C. After 24 hours, the left lung was transplanted. Regional
      pulmonary blood flow was assessed by injection of colored microspheres into the
      right atrium using the reference withdrawal technique. Measurements of regional
      pulmonary blood flow were conducted twice in donors and recipients (baseline and
      3 hours after reperfusion). Tissue samples from five distinct regions (apical,
      medial, dorsal, ventral, and lateral) were taken to assess regional pulmonary
      blood flow and wet-dry ratios. RESULTS: The relative (per thousand Confidence
      Intervals/100 mg dry weight) regional pulmonary blood flow was significantly
      reduced in the transplanted lung but not in the native organ. This reduction was
      most pronounced in apical regions and smallest in regions close to the hilum.
      Edema formation occurred in both lungs, as judged from wet-to-dry ratios of lung
      tissue specimen. CONCLUSIONS: Two separate processes can be observed after single
      lung transplantation: (1) reduced regional pulmonary blood flow, which is a
      regional phenomenon restricted to the transplanted organ, and (2) extensive edema
      affecting both the transplanted and the native lung.

PMID- 11834015
TI  - C1-esterase inhibitor reduces reperfusion injury after lung transplantation.
AB  - BACKGROUND: Activation of the complement system and polymorphonuclear
      neutrophilic leukocytes plays a major role in mediating reperfusion injury after
      lung transplantation. We hypothesized that early interference with complement
      activation would reduce lung reperfusion injury after transplantation. METHODS:
      Unilateral left lung autotransplantation was performed in 6 sheep. After hilar
      stripping the left lung was flushed with Euro-Collins solution and preserved for
      2 hours in situ at 15 degrees C. After reperfusion the right main bronchus and
      pulmonary artery were occluded, leaving the animal dependent on the reperfused
      lung (reperfused group). C1-esterase inhibitor group animals (n = 6) received 200
      U/kg body weight of C1-esterase inhibitor as a short infusion, half 10 minutes
      before, the other half 10 minutes after reperfusion. Controls (n = 6) underwent
      hilar preparation only. Pulmonary function was assessed by alveolar-arterial
      oxygen difference and pulmonary vascular resistance. The release of beta-N
      acetylglucosaminidase served as indicator of polymorphonuclear neutrophilic
      leukocyte activation. Extravascular lung water was an indicator for pulmonary
      edema formation. Biopsy specimens were taken from all groups 3 hours after
      reperfusion for light and electron microscopy. RESULTS: In the reperfused group,
      alveolar-arterial oxygen difference and pulmonary vascular resistance were
      significantly elevated after reperfusion. All animals developed frank alveolar
      edema. The biochemical marker beta-N-acetylglucosaminidase showed significant
      leukocyte activation. In the C1-esterase inhibitor group, alveolar-arterial
      oxygen difference, pulmonary vascular resistance, and the level of
      polymorphonuclear neutrophilic leukocyte activation were significantly lower.
      CONCLUSIONS: Treatment with C1-esterase inhibitor reduces reperfusion injury and
      improves pulmonary function in this experimental model.

PMID- 11834016
TI  - Full thoracoscopic approach for surgical management of invasive pulmonary
      aspergillosis.
AB  - BACKGROUND: Invasive pulmonary aspergillosis (IPA) is a frequent and serious
      infection occurring in patients with hematologic malignancies and allogenic stem
      cell transplant (SCT) recipients, causing a high mortality rate. We report the
      use of full thoracoscopic management in 19 patients. METHODS: Nineteen patients
      (mean age 27 years) with diagnosed or probable IPA were operated on. Seventeen
      had an hematologic malignancy and 2 had a refractory aplastic anemia. Nine
      patients had undergone an allogenic SCT that was complicated by a graft-versus
      host disease in 5 patients. In 3 patients, SCT was pending. All patients had
      preoperative systemic antifungal therapy for at least 2 weeks. Fifteen patients
      had only one lesion, whereas 4 had two lesions. Eight patients had an absolute
      neutrophil count less than 3,000 and 2 less than 1,000, and 9 were thrombopenic
      (platelet count <60,000) at the day of surgery. Wedge resections were performed
      in 7 patients and lobectomies were performed for the other 12. For the latter, an
      open approach via posterolateral thoracotomy was decided upon in only 1 patient.
      For the other 11 lobectomies, a mini-thoracotomy was needed in 3 cases for
      intraoperative difficulties. Conversion to conventional thoracotomy was necessary
      for 2 of these patients. In total, out of the 19 patients, 15 had a total
      endoscopic approach, 3 had a thoracotomy, and 1 had a video-assisted approach.
      RESULTS: There was no intraoperative mortality. In the group of wedge resections,
      no intraoperative or postoperative complication occurred. In the lobectomy group,
      three hemorrhages occurred during dissection of the pulmonary artery in the
      fissure, leading to conversion to a mini-thoracotomy in 2 patients and to a
      classic posterolateral thoracotomy in 1 patient. There were two minor
      complications: one pneumothorax and one mild pleural effusion. CONCLUSIONS: In
      these debilitated and immunocompromised patients, a full thoracoscopic resection
      of fungal infection is feasible, even for lobectomies. It allows a simpler
      postoperative course and minimizes sequelae.

PMID- 11834017
TI  - Inter-observer variability in systematic nodal dissection: comparison of European
      and Japanese nodal designation.
AB  - BACKGROUND: Systematic nodal dissection is accepted as an important component of
      the intrathoracic staging of patients undergoing thoracotomy for lung cancer.
      Several lymph node maps have been proposed in an attempt to ensure uniformity in
      designating lymph node stations. The Japan Lung Cancer Society has published
      detailed definitions for each nodal station adopting the Naruke map. However,
      since these definitions had not been interpreted into other languages, they have
      not been universally accepted. The objective of this study was to assess the
      inter-observer variability in the interpretation of lymph node stations. METHODS:
      A total of 424 lymph node stations were removed from 41 patients undergoing
      thoracotomy for non-small cell lung cancer. All nodal stations were labeled using
      the Naruke map. As each station was excised, it was designated in a blind fashion
      by one of two surgeons trained in the UK and one surgeon trained in Japan. The
      designation accorded to each nodal station was analyzed. RESULTS: The total
      concordance was 68.5% (right side 67.0%, left side 69.9%). The concordance rate
      for individual nodal stations varied from 0% to 100%. Considerable discordance
      existed between the Japanese and European surgeons in the designation of nodal
      stations 2, 4, 8 and N1 station 12. In 14 (34.1%) patients, discordance in the
      labeling of lymph nodes led to disease being categorized as N1 by one observer,
      whereas the other considered the same nodes to be N2. CONCLUSIONS: Considerable
      discordance in the designation of nodal station has been demonstrated. We would
      expect similar inter-observer variability elsewhere between surgeons,
      institutions, or countries. More detailed nodal charts and precise, easily
      understood definitions of nodal stations are needed for intrathoracic staging.
      The first English version of the Japan Lung Cancer Society staging manual goes
      some way to address this.

PMID- 11834018
TI  - Extended cervical mediastinoscopy in the diagnosis of anterior mediastinal
      masses.
AB  - BACKGROUND: Although transthoracic needle biopsy (TNB) has been the preferred
      method for the diagnosis of anterior mediastinal masses, it has inherent
      limitations in accuracy. In particular, lymphoma and thymoma are diagnosed less
      reliably using needle biopsy. Videothoracoscopy has been advocated as an
      alternative method for diagnosis. Our goal was to assess the usefulness of
      extended cervical mediastinoscopy (ECM) in the diagnosis of anterior mediastinal
      masses. METHODS: The ECM technique was performed in 9 patients in whom TNB and
      Tru-cut biopsies had been inefficient for histologic diagnosis. All lesions were
      in the anterior mediastinum. Extended cervical mediastinoscopy was carried out
      using the same incision as in a standard cervical mediastinoscopy and dissection
      was performed behind the sternum as previously published. Mean operative time was
      50 minutes (range 40 to 70 minutes) and mean hospital stay was 8 hours (range 5
      to 36 hours). RESULTS: Diagnosis of lymphoma in 4 cases, thymoma in 3 cases, and
      thymic hyperplasia in 2 cases were obtained by ECM. In 1 of 2 patients with
      suspected thymoma who underwent resectional surgical procedures, final histologic
      diagnosis was non-small cell lung carcinoma. There was no surgical mortality or
      intraoperative complication. One patient had minimal pneumothorax requiring no
      intervention. CONCLUSIONS: We conclude that ECM in the diagnosis of anterior
      mediastinal masses is technically feasible and provides an alternative to the
      conventional approaches in patients with paraaortic or aortopulmonary masses.

PMID- 11834019
TI  - Characteristics and prognosis of resected T3 non-small cell lung cancer.
AB  - BACKGROUND: T3 tumors can be divided into several subgroups depending on the type
      of anatomical structure invaded: chest wall, mediastinal pleura, or main
      bronchus. The aim of this study was to analyze the characteristics and prognosis
      of each subgroup of T3 tumors. METHODS: The results of surgical treatment were
      retrospectively analyzed for 261 patients with T3 non-small cell lung cancer
      invading either the mediastinal pleura or parietal pericardium by direct
      extension (mediastinal pT3, n = 68), or main bronchus (bronchial pT3, n = 68), or
      chest wall (chest wall pT3, n = 125) that were operated on between 1984 and 1996.
      Complete resection including radical mediastinal lymph node dissection was
      intended in all patients. One patient had segmentectomy, 91 had lobectomy
      (34.9%), and 169 had pneumonectomy (64.8%). One hundred and fifty-eight patients
      received adjuvant radiation therapy and 7 patients received both adjuvant
      chemotherapy and radiation therapy. Actuarial survival curves were drawn using
      the Kaplan-Meier method and risk factors for late death were identified. RESULTS:
      In-hospital mortality was 6.1%. Follow-up was 98% complete. Global 5-year
      survival was 28%, with survival being not significantly different among the three
      subgroups: 34.9%, 30.6%, and 22.5% (p = 0.19) in the bronchial pT3, mediastinal
      pT3, and chest wall pT3 subgroups, respectively. Resection margins were
      microscopically invaded in 33 patients (12.6%). Seventy-four patients had N1
      involvement (28.4%) and 78 patients had N2 involvement (29.8%). N0 involvement
      was more prevalent in the chest wall pT3 subgroup, whereas N1 involvement was
      more prevalent in the bronchial pT3 subgroup and N2 involvement was more
      prevalent among patients with mediastinal invasion. Pathologic factors
      influencing the 5-year survival were tumor size (p = 0.03) and N involvement (p =
      0.003). Histology, type of surgical resection (lobectomy versus pneumonectomy),
      and use of adjuvant therapy did not influence survival significantly.
      CONCLUSIONS: Five-year survival was not significantly different among the three
      subgroups of pT3 non-small cell lung cancer, although bronchial pT3 tumors tended
      to have a better prognosis and chest wall pT3 tumors tended to have a worse
      prognosis. The pathologic characteristics of each pT3 subgroup seems different.
      Further research is warranted to explore the pathologic and biological factors
      influencing prognosis for each pT3 subgroup.

PMID- 11834020
TI  - An initial experience with FDG-PET in the imaging of residual disease after
      induction therapy for lung cancer.
AB  - BACKGROUND: The 2-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET)
      imaging is an advance over computed tomography alone in the staging of untreated
      nonsmall cell lung cancer (NSCLC). Aside from one 9-patient study, there are no
      data comparing FDG-PET imaging with surgical staging of NSCLC after induction
      therapy. METHODS: We reviewed our institutional experience with FDG-PET imaging
      followed by surgical staging of nonsmall cell lung cancer after induction
      therapy. A nuclear physician blinded to surgical findings reviewed the FDG-PET
      scans and assigned a clinical TNM stage. A thoracic surgeon assigned a pathologic
      TNM stage. Then the clinical TNM stage and the pathologic TNM stage were
      compared. RESULTS: Fifty-six patients (30 males and 26 females; median, age 60)
      with nonsmall cell lung cancer underwent chemotherapy (40 patients),
      chemoradiation (11 patients), or radiation alone (5 patients) followed by PET and
      operations. PET had a positive predictive value of 98% for detecting residual
      viable disease in the primary tumor. PET over-staged nodal status in 33% of
      patients, under staged nodal status in 15%, and was correct in 52%. PET correctly
      classified all patients with M1 disease. CONCLUSIONS: Positron emission
      tomography after induction therapy accurately detects residual viable primary
      tumor, but not the involvement of mediastinal lymph nodes.

PMID- 11834021
TI  - Esophageal atresia: historical evolution of management and results in 371
      patients.
AB  - BACKGROUND: It has been more than 50 years since the first successful surgical
      reconstruction of esophageal atresia was performed in The Netherlands. We
      reviewed the historical changes in management and treatment results of patients
      born with esophageal atresia. METHODS: We developed and analyzed a database of
      371 consecutive patients treated for esophageal atresia in our center between
      1947 and 2000. RESULTS: The mean birthweight decreased from 2,723 g (1947 to
      1968) to 2,494 g (1994 to 2000), the mean gestational age decreased from 39 weeks
      (1947 to 1968) to 37 weeks (1994 to 2000). The number of patients with associated
      congenital malformations increased from 34% (1947 to 1968) to 66% (1994 to 2000).
      Most patients underwent primary repair of their atresia. Clinically significant
      tracheomalacia was present in 34 of 269 patients (13%). Gastroesophageal reflux
      was present in 90 of 277 patients (33%). Mortality decreased from 61% (1947 to
      1968) to 11% (1994 to 2000). CONCLUSIONS: The patients who are treated nowadays
      for esophageal atresia in a pediatric surgical center are born earlier, weigh
      less, and have more associated anomalies than those treated 50 years ago. Still,
      the mortality rate is much lower thanks to earlier diagnosis, better supportive
      care and improved surgical techniques. Therefore, further significant reduction
      will be difficult to achieve.

PMID- 11834022
TI  - Pulmonary venous obstruction after total cavopulmonary connection in heterotaxy.
AB  - Pulmonary venous obstruction is a rare complication after total cavopulmonary
      connection by intraatrial grafting. We experienced this complication in two
      patients. In one of them, a large prosthesis produced inflow obstruction of the
      dominant ventricle and was successfully replaced with a smaller tube. In the
      other patient, the intraatrial tube had become severely adherent to the common
      pulmonary venous orifice and was removed entirely. Conversion to an extracardiac
      Fontan circulation was later successfully established.

PMID- 11834024
TI  - Antero-axillary access for hypoplastic aortic arch repair.
AB  - A 16-year-old adolescent presented with systemic hypertension due to a hypoplasia
      of the aortic arch resulting in a significant stenosis. In childhood, he
      underwent surgery for aortic coarctation through a left posterolateral
      thoracotomy. We present the successful repair of the complete aortic arch that
      could be achieved applying a patch plasty of bovine pericardium through an
      anteroaxillary thoracotomy.

PMID- 11834023
TI  - Congenital mitral-aortic discontinuity.
AB  - Mitral-aortic (M-A) discontinuity is an uncommonly observed congenital
      malformation. From the embryologic point of view, it is a failure of the superior
      endocardial cushion of the A-V canal reach and insert into the aortic root (the
      mitral-aortic fibrous trigone). It should be differentiated from aorto-left
      ventricular discontinuity, a complication of endocarditis with excavating
      abscesses without boundaries. In congenital mitral-aortic discontinuity, the
      anterior leaflet of the mitral valve fails to insert into the aortic root. We
      report our experience with 2 patients. In patient 1, the severe left ventricular
      outflow obstruction was mainly caused by the mobile anterior leaflet of the
      mitral valve.

PMID- 11834025
TI  - Multidose cardioplegia in a complex arterial switch procedure.
AB  - Integrated cardioplegia techniques have gained wide acceptance by surgeons
      performing adult cardiac surgery, because patients being referred are likely to
      have poor ventricular function and energy-depleted hearts. In addition, the
      increasing complexity of available procedures has led to an increased threat of
      reperfusion injury and calcium contracture ("stone heart") after prolonged
      ischemia. In this report, we describe the case of a newborn with transposition of
      the great arteries that survived almost 6 hours of ischemic time and has normal
      ventricular function postoperatively. We attribute this outcome to the myocardial
      protection employed throughout the procedure which allowed successful correction
      of a technical problem.

PMID- 11834026
TI  - Absent pulmonary valve syndrome with aortic regurgitation in a 50-year-old man.
AB  - A 50-year-old man was diagnosed as having absent pulmonary valve syndrome with
      aneurysmal dilatation of the pulmonary arteries. He also had a large subaortic
      ventricular septal defect and severe aortic regurgitation. He underwent
      successful intracardiac repair and aortic valve replacement. This case is
      presented in view of its rarity and controversies in the surgical management.

PMID- 11834027
TI  - Aortoscopy: a less invasive intraoperative method to assess the aortic valve.
AB  - Surgical management of mild aortic stenosis coexisting with severe coronary
      artery disease remains controversial. Direct examination of the aortic root under
      these circumstances may be decisive. At present, intraoperative assessment of the
      aortic valve requires an aortic incision which, in itself, may increase the risk
      of intraoperative complications, particularly when this portion of the aorta is
      needed to construct proximal graft anastomoses. We present a simple aortoscopic
      method for direct intraoperative assessment of the aortic valve while performing
      coronary bypass grafting that obviates the need for aortic incisions.

PMID- 11834028
TI  - Huge left atrial thrombus with mitral stenosis in congenital factor XII
      deficiency.
AB  - Factor XII deficiency has been reported to be a risk factor for thromboembolism
      as a result of inactivation of fibrinolysis. We describe a case of a huge left
      atrial thrombus with mitral stenosis, which was successfully removed surgically
      in a Factor XII deficient patient.

PMID- 11834029
TI  - Endovascular stent grafting of the descending thoracic aorta after arch repair in
      acute type A dissection.
AB  - An endovascular stent graft was successfully deployed to the primary entry site
      in the proximal descending thoracic aorta after total aortic arch replacement
      using the "elephant trunk" technique in acute type A aortic dissection. The
      residual false lumen of the descending aorta was thrombosed completely after
      stent grafting. The elephant trunk was feasible for a proximal landing zone for
      stent grafting of the descending aorta. Stent grafting in combination with aortic
      arch replacement was a safe and effective procedure, and may be an alternative
      choice in carefully selected patients with type A aortic dissection.

PMID- 11834030
TI  - Aortic valve reimplantation in ascending aortic aneurysm: risk factors for early
      valve failure.
AB  - BACKGROUND: Aortic root reconstruction by reimplantation of the native valve
      represents a new therapeutic option for ascending aortic aneurysms. Information
      about long-term follow-up is limited, and possible predictors for failure of
      reconstruction have not been evaluated so far. METHODS: After aortic valve
      reimplantation 101 patients were followed in a prospective observational study.
      From this cohort the first 75 consecutive patients with a complete 1-year follow
      up were chosen for further analysis. Clinical and echocardiographic data were
      obtained preoperatively, intraoperatively, and early postoperatively, as well as
      after 1 year of follow-up. RESULTS: No mortality was observed within the first 30
      days. There were 52 male patients, mean age was 49.1+/-20.6 years, observation
      period was 35.6+/-20.6 months, and Marfan's syndrome was present in 22 patients.
      Although in 67 patients a stable valve function could be demonstrated, 5 patients
      presented with mild aortic insufficiency or had to be operated on again for
      secondary valve failure (n = 3). Analyzing possible demographic, disease-related,
      and procedure-related risk factors in a multivariable approach, only level of
      coaptation within the graft (as assessed by echocardiography) could be identified
      as being related to the subsequent development of aortic insufficiency.
      Coaptation level within the tube graft (type A) resulted in a mean aortic
      regurgitation grade of 0.3+/-0.5 as compared with a mean grade of 2.5+/-0.6 for a
      coaptation type C (below the prosthesis; p < 0.001). CONCLUSIONS: Aortic valve
      reimplantation is a promising alternative to alloprosthetic composite
      replacement. A level of coaptation within the tube graft is essential to achieve
      valve competence.

PMID- 11834031
TI  - Aortic arch replacement for recurrent cerebral embolization.
AB  - Replacement of the aortic arch for atheroma with cerebral embolization is in its
      infancy. The appropriateness of such intervention is controversial. Over a 10
      month period, a 58-year-old woman suffered multiple debilitating cerebral
      vascular accidents manifested by motor, sensory, and memory deficits and
      documented by computed tomographic scanning and magnetic resonance imaging.
      Carotid and vertebral arteries were free of arteriosclerotic disease.
      Transesophageal echocardiography demonstrated two large atheromas with friable,
      pedunculated forms, one in the aortic arch and one in the very proximal
      descending thoracic aorta. Transcranial ultrasound revealed recurrent cerebral
      microembolic events. Cerebrovascular events continued, and the atheromas
      increased in size, despite treatment with Coumadin and aspirin. Under deep
      hypothermic arrest, the segment of the aortic arch harboring the atheroma was
      excised and replaced with a Dacron graft. Repeat transcranial ultrasound revealed
      cessation of embolic signals. All cerebrovascular events ceased. No further
      anticoagulation therapy was required. The patient has made substantial recovery
      from the preoperative deficits and continues to do well 1 year after aortic arch
      replacement. Resection of mobile aortic arch atheromas is likely to become
      increasingly important in the future as transesophageal echocardiography leads to
      their more common identification as a cause of cerebral ischemic events.

PMID- 11834032
TI  - Delayed surgical management of a traumatic aortic arch injury.
AB  - We report successful management of a blunt traumatic injury to the aortic arch
      with intentionally delayed surgical repair. The aorta was repaired after the
      stabilization of other, potentially fatal, traumatic injuries.

PMID- 11834034
TI  - Coronary artery spasm and ventricular fibrillation after off-pump coronary
      surgery.
AB  - Native coronary artery or bypass graft spasm is a rare cause of acute myocardial
      infarction after coronary artery bypass grafting. This report presents
      angiographic documentation of native coronary artery spasm following successful
      multivessel off-pump coronary revascularization, which caused myocardial ischemia
      leading to inferior wall myocardial infarction and ventricular fibrillatory
      arrest.

PMID- 11834033
TI  - Carbon dioxide embolism during minimally invasive vein harvesting.
AB  - Gas embolism is a known complication of minimal access procedures in which carbon
      dioxide insufflation is used. We report a case of significant venous and right
      heart gas embolization, which occurred during performance of routine minimally
      invasive vein harvesting. This was manifest by hemodynamic deterioration
      secondary to transmission by a patent foramen ovale into the left heart and
      coronary circulation. Techniques to predict, diagnose, and prevent this rare but
      potentially fatal complication of minimally invasive vein harvesting are
      suggested.

PMID- 11834035
TI  - Ptosis postcardiac surgery: a case of pituitary apoplexy.
AB  - We present a patient in whom ptosis and third cranial nerve palsy developed
      postcoronary artery bypass grafting, and discuss the management of pituitary
      apoplexy postcardiac surgery.

PMID- 11834036
TI  - Perforating Barrett's ulcer resulting in a life-threatening esophagobronchial
      fistula.
AB  - Perforating benign ulcer is a very rare complication of Barrett's esophagus. This
      report presents the management of a patient with a Barrett's ulcer that
      penetrated into the left mainstem bronchus resulting in a life-threatening
      bronchial esophageal fistula. This rare complication was successfully managed by
      using a staged surgical approach, which combined the principles used for treating
      benign esophagorespiratory fistulas and perforating Barrett's ulcers.

PMID- 11834037
TI  - Necrotizing soft tissue infection of the chest wall.
AB  - Necrotizing soft tissue infection of the chest wall is a relatively rare but
      highly lethal surgical condition that has received little attention in the
      literature. The case of a 21-year-old female patient affected by this rare
      infection is reported. Our recent experience and literature data suggest that
      chest wall necrotizing soft tissue infection spreads rapidly and is highly
      lethal. High index of suspicion, early diagnosis, and aggressive approach are
      essential to its successful treatment.

PMID- 11834038
TI  - Donor transfer of pulmonary coccidioidomycosis in lung transplantation.
AB  - Transplant recipients living in endemic areas are at high risk of aerosol
      transmitted fungal infections because of environmental exposure while on
      immunosuppressive drugs, as well as reactivation of latent infection from either
      the patient's or the donor's organs. The latter may account for early development
      of coccidioidomycosis after transplantation. We describe a case of pulmonary
      coccidioidomycosis in a lung transplant recipient who acquired the infection from
      the donor lung and presented with fulminant pneumonia in the immediate
      postoperative period.

PMID- 11834039
TI  - Bilateral lung transplantation using a donor with a tracheal right upper lobe
      bronchus.
AB  - We report on a case of successful bilateral sequential lung transplantation using
      a donor with the right upper lobe bronchus arising from the trachea. After en
      bloc donor lung retrieval, the right bronchial stump was fashioned to create one
      lumen including the bronchus intermedius and the aberrant right upper lobe
      bronchus. A carinoplasty was performed in the recipient with resection of a
      portion of the lateral wall of trachea. The anastomosis was completed using a
      telescoping technique without any complication. This case demonstrates the
      possibility of successfully using donor lungs with such anatomic abnormality for
      transplantation.

PMID- 11834040
TI  - Tracheobronchoplasty for resection of lung cancer arising from a tracheal
      bronchus.
AB  - Tracheal bronchus is a rare anomoly wherein a bronchus arises directly from the
      trachea and supplies the right upper lobe. We had a case of lung cancer arising
      from a tracheal bronchus with invasion into the trachea. Tracheobronchoplasty was
      needed for complete resection of the tumor. Because of the anatomical
      characteristics of the tracheal bronchus, special surgical techniques for
      resection of the neoplasm were needed.

PMID- 11834041
TI  - Dyspnea lusoria: compression of the pulmonary artery by a Kommerell's
      diverticulum.
AB  - We report a rare case of Kommerell's diverticulum presenting as dyspnea on
      exertion. After careful physical examination, selective imaging tests
      demonstrated a significant flow abnormality in the left pulmonary artery caused
      by an aneurysm of the descending aorta in the area of the ligamentum arteriosum.

PMID- 11834042
TI  - Complete resorption of a thoracic aortic aneurysm after stent-graft placement.

PMID- 11834043
TI  - Left internal mammary artery to pulmonary artery fistula after minimally invasive
      coronary bypass.

PMID- 11834044
TI  - Aortic valve exposure through a combined right atrial-ascending aortic approach
      in redo cases.
AB  - The expanded use of tissue valves in the aortic position lead to an increased
      number of reoperations in cases o valve failure. The approach to an aortic
      prosthesis can be difficult because of heavy adhesions, especially if biological
      glue was used in the first procedure and the interval between the first and
      second operation is short.

PMID- 11834045
TI  - Epicardial ablation of atrial fibrillation on the beating heart without
      cardiopulmonary bypass.
AB  - The Cox-Maze procedure is the gold standard in surgical treatment of atrial
      fibrillation. Alternative techniques using cryoablation, radiofrequency, or
      microwaves have been proven to be equally effective. However, up to now, all
      techniques require the opening of the atria and, hence, the use of extracorporeal
      circulation. We describe a technique to perform epicardial ablation of atrial
      fibrillation on the beating heart without the use of cardiopulmonary bypass.

PMID- 11834046
TI  - Biologic glue-molded "bio-mini-paddle" electrode used for atrial and ventricular
      pacing and defibrillation.
AB  - Atrial and ventricular dysrhythmias developing after cardiac operation further
      reduce cardiac output, posing a serious problem for postoperative management. We
      have developed a "bio-mini-paddle" electrode designed to be attached directly to
      the myocardium for atrial or ventricular defibrillation and pacing for
      intraoperative and postoperative cardiac management. We use fibrin glue for the
      paddle, which is biodegradable. The characteristics of this unique paddle were
      examined using mongrel dogs.

PMID- 11834048
TI  - First-stage palliation for hypoplastic left heart syndrome in the twenty-first
      century.
AB  - Improved understanding of the postoperative physiology and experience with the
      surgical techniques and perioperative care of patients with hypoplastic left
      heart syndrome have resulted in improved outcomes. Over the past few years,
      numerous modifications to the intraoperative and postoperative management of
      these patients have been described. It is likely that in combination, these
      modifications and better understanding of the unique physiology after the Norwood
      procedure are responsible for decreasing early mortality. This review describes
      and discusses the current surgical and medical management of patients undergoing
      first-stage palliation for hypoplastic left heart syndrome and its variants.

PMID- 11834047
TI  - Intravenous milrinone in cardiac surgery.
AB  - Phosphodiesterase inhibitors including milrinone produce positive inotropic
      effects by slowing the hydrolysis of cyclic adenosine monophosphate in the
      myocardium. With a loading dose of 50 microg/kg followed by an infusion of 0.5
      microg x kg(-1) x min(-1), milrinone increases stroke volume index and left
      ventricular velocity of circumferential fiber shortening after weaning from
      cardiopulmonary bypass. Milrinone has potential for the treatment and prevention
      of internal mammary artery spasm because of its vasodilative effect, which is
      similar to that of papaverine, and is a potent pulmonary vasodilator for patients
      with right ventricular dysfunction and pulmonary vasoconstriction. Low-dose
      milrinone may have antiinflammatory properties and potentially can improve
      splanchnic perfusion.

PMID- 11834049
TI  - Mitral stenosis after mitral valve repair for non-rheumatic mitral regurgitation.
AB  - BACKGROUND: Mitral stenosis after mitral valve repair for non-rheumatic mitral
      regurgitation is rare. METHODS: From 1990 to 1999, 478 patients had mitral valve
      repair for myxomatous and 40 patients had mitral valve repair for ischemic mitral
      regurgitation. The Carpentier annuloplasty ring (Edwards Lifesciences, Irvine,
      CA) was used in 72 patients, the Duran ring (Medtronic, Minneapolis, MN) in 152,
      a posterior band in 221 and no ring or band in 73 patients. RESULTS: Four
      patients developed mitral stenosis late after mitral valve repair: 2 for
      myxomatous disease and 2 for ischemic mitral regurgitation. All 4 patients had
      Duran annuloplasty rings (sizes 25 to 31). The diagnosis of mitral stenosis was
      made by Doppler echocardiography. The mitral valve area in these 4 patients
      decreased from 2.7 cm2 (range, 2.3 to 3.2 cm2) early postoperatively to 0.85 cm2
      (0.4 to 1.2 cm2) after a mean follow-up of 66 months (range, 38 to 110 months).
      Three patients had mitral valve replacement and the etiology of the mitral
      stenosis was the same in all patients (ie, pannus overgrowth on the annuloplasty
      ring with extension onto both leaflets rendering them stiff and immobile). The
      fourth patient had a mitral valve area of 1.2 cm2, which was mildly symptomatic
      with normal pulmonary artery pressure, and this patient has not had reoperation.
      CONCLUSIONS: Mitral stenosis may develop after mitral valve repair for myxomatous
      disease or ischemic mitral regurgitation when a Duran ring is used for
      annuloplasty. The stenosis is caused by pannus on the annuloplasty ring with
      extension onto the leaflets.

PMID- 11834050
TI  - "Hearts for all": a humanitarian association for the promotion of cardiology and
      cardiac surgery in developing countries.

PMID- 11834051
TI  - Induced ventricular fibrillation in the management of aortic arch trauma.

PMID- 11834052
TI  - Cellular myoplasty: what are we really trying to achieve?

PMID- 11834053
TI  - Right ventricle to pulmonary artery connection after the Ross procedure: is it
      really a concern?

PMID- 11834054
TI  - Risk of coronary artery occlusion with snares during OPCAB.

PMID- 11834055
TI  - LIMA use in the STS database: a correction.

PMID- 11834056
TI  - Assessing the radial artery for a coronary bypass conduit.

PMID- 11834057
TI  - Dynamic cardiomyoplasty: "the truth that dare not speak its name".

PMID- 11834058
TI  - Time to remember P. K. Sen's legacy.

PMID- 11834059
TI  - Durability of the intercostal muscle pedicle.

PMID- 11834060
TI  - Is "steal" present in hemodialysis patients with ipsilateral internal mammary
      graft?

PMID- 11834061
TI  - Clinical outcome in patients with 19-mm and 21-mm St. Jude aortic prostheses:
      comparison at long-term follow-up.
AB  - BACKGROUND: Small-sized prostheses for aortic valve replacement may result in
      residual left ventricular outflow tract obstruction. Aim of the study was to
      verify whether implantation of 19-mm versus 21-mm St. Jude Medical standard
      prostheses (St. Jude Medical, Inc, St. Paul, MN) influences long-term clinical
      outcome. METHODS: Two hundred twenty-nine patients who underwent aortic valve
      replacement with 19 mm (group 1, 53 patients) or 21-mm St. Jude Medical standard
      prostheses (group 2, 176 patients) were included in the study. Mean follow-up of
      current survivors was 10+/-4 years. RESULTS: Operative mortality was 7.5% in
      group 1 and 8.5% in group 2. At discharge, an important patient-prosthesis
      mismatch (effective orifice area index < or = 0.60 cm2/m2) was present in 18% of
      group 1 versus 5% in group 2 (p = 0.004). Among patients with body surface area
      less than 1.70 m2, such mismatch was present in 15% of group 1 versus 2% of group
      2 (p = 0.008). At last follow-up New York Heart Association (NYHA) functional
      class (p < 0.001), left ventricular mass reduction (p = 0.02), mean (p = 0.002)
      and peak transprosthetic gradients (p < 0.001), and effective orifice area index
      (p = 0.005) were significantly better in group 2. Freedom from sudden death
      (92%+/-5% vs 99%+/-1%, p = 0.01), valve-related death (84%+/-6% vs 90%+/-5%, p =
      0.02), and cardiac events (56%+/-13% vs 86%+/-4%, p = 0.008), were significantly
      lower in group 1. Effective orifice area index was an independent predictor of
      late cardiac events. CONCLUSIONS: Although long-term results after aortic valve
      replacement with small-sized St. Jude Medical standard prostheses are
      satisfactory, 19-mm valve recipients show a high prevalence of important patient
      prosthesis mismatch with less evident functional improvement and higher rate of
      cardiac events, suggesting a very cautious use of this prosthesis.

PMID- 11834062
TI  - Long-term results with triple valve surgery.
AB  - BACKGROUND: Whether to use biological or mechanical prostheses and whether to
      repair or replace the tricuspid valve during primary and reoperative triple valve
      surgery remains controversial. The objective of the present study was to review
      our experience with primary and reoperative triple valve surgery using
      CarboMedics (CM) and Carpentier-Edwards (C-E) heart valves. METHODS: All 73
      patients undergoing triple valve surgery since 1982 were prospectively followed
      at the Montreal Heart Institute valve clinic. Aortic valve replacement was
      performed with CM prostheses (57 patients) and with C-E prostheses (16 patients).
      Mitral valve replacement was performed with mechanical prostheses (56 patients)
      and with biological valves (14 patients). Mitral valve repair was done in 3
      patients. Tricuspid valve annuloplasty or commissurotomy or both were performed
      in 66 patients and the tricuspid valve was replaced in 7 patients. Patient
      survival, complications, and the type of valve procedures were analyzed. RESULTS:
      Thirty patients averaging 62+/-10 years of age underwent primary triple valve
      surgery and 43 patients averaging 60+/-10 years of age underwent reoperative
      triple valve surgery (p = 0.5). Tricuspid repair consisted of annuloplasty with
      the Bex linear reducer (n = 47), the C-E ring (n = 13), or the De Vega technique
      (n = 5). Tricuspid valve replacement was done using the C-E pericardial
      prostheses. The 30-day mortality was 17% and 12% in patients with primary and
      reoperative surgery, respectively (p = 0.5) and patient survival averaged 80%+/
      7%, 75%+/-8%, and 41%+/-15%, and 70%+/-7%, 57%+/-9%, and 50%+/-10%, respectively
      1, 5, and 10 years following surgery (p = 0.5). The freedom rate from
      thromboembolism and from bleeding complications were 87%+/-6% and 95%+/-3% in
      primary and reoperative patients, respectively, 5 years following surgery.
      CONCLUSIONS: Triple valve surgery, either as a primary or a reoperative
      procedure, results in acceptable long-term survival with both mechanical and
      biological prostheses.

PMID- 11834063
TI  - Apical ventricular septal defects: follow-up concerning anatomic and surgical
      considerations.
AB  - BACKGROUND: Apical ventricular septal defects (VSDs) are difficult to visualize
      and close transatrially. We described their distinctive anatomic features, which
      have seldom been documented angiocardiographically and pathologically, in order
      to develop an effective approach for their surgical management. METHODS: Fourteen
      postmortem cases, two explanted hearts, 9 successfully operated patients, and 1
      unoperated living patient were included in this report. Angiocardiographic
      documentation of the apical VSD was available in 14 of 16 (87.5%) of the
      postmortem and transplanted cases, and in 6 of 10 (60%) of the living patients.
      Echocardiograms were available in 23 of all 26 cases (88%). RESULTS: Severe
      associated malformations were present in 14 of 16 (87%) of the pathologically
      documented cases. Large VSDs allowed extensive communication between the left
      ventricular and the right ventricular sinuses in 4 patients. In 12 of the
      pathologically documented cases and in the 10 living patients, the left
      ventricular apex communicated with the right ventricular apical infundibular
      recess. CONCLUSIONS: Extremely large apical VSDs with severe biventricular
      dysplasia and dysfunction may require cardiac transplantation. Large apical VSDs
      can be successfully closed through a small apical infundibulotomy. This approach,
      applicable even in small infants, can avoid pulmonary artery banding or left
      ventriculotomy.

PMID- 11834064
TI  - Fontan's operation: is aspirin enough? Is coumadin too much?
AB  - BACKGROUND: Thromboembolism after Fontan's operation is attributed to low flow
      states, stasis in venous pathways, right to left shunts, blind cul-de-sacs,
      prosthetic materials, atrial arrhythmias, and hypercoagulable states. We assessed
      the efficacy of a strategy to reduce thromboembolic events including aspirin
      anticoagulation. METHODS: From January 1996 through December 2000, 72 patients
      underwent Fontan procedures. Management included (1) avoidance of direct caval
      cannulation and central venous lines, (2) inotropic support for 48 to 72 hours to
      optimize cardiac output, (3) aortopulmonary anastomosis or suture closure of
      patent pulmonary valves, and (4) administration of aspirin (81 mg per day)
      beginning on postoperative day one. No other anticoagulation strategies were
      used. Surveillance included intraoperative and postoperative transesophageal
      echo, transthoracic echo at discharge, at first reevaluation, and at 6 month
      intervals, and catheterization 1 year after surgery. RESULTS: There were no early
      or late deaths. Follow-up was completed with 2,882 patient-months and a mean of
      40 months. There were no documented thromboembolic events; however, all
      suspicious occurrences were investigated by echo and brain imaging. There were no
      hemorrhagic events or aspirin-related complications. CONCLUSIONS: Low dose
      aspirin can be used safely in young patients with Fontan connections. At
      intermediate follow-up, the strategies described appear effective in preventing
      thromboembolic complications. Routine use of more aggressive anticoagulation
      regimens seems unwarranted.

PMID- 11834065
TI  - Surgical results of double-orifice left atrioventricular valve associated with
      atrioventricular septal defects.
AB  - BACKGROUND: Double-orifice left atrioventricular valve (LAVV) is a rare but
      surgically important anomaly, which is regarded as a risk factor for surgical
      correction of atrioventricular septal defects (AVSDs). METHODS: Of 209
      consecutive patients with AVSDs, double-orifice LAVV was identified in 19
      patients (9.1%, including 7 infants). Preoperative LAVV function, surgical
      procedures and results, incidence of postoperative LAVV dysfunction and
      reoperations were reviewed and compared between patients with this valve
      malformation (group I, n = 19) and those without it (group II, n = 190). RESULTS:
      There were no operative or late deaths in group I. Preoperative LAVV function was
      similar in both groups. The cleft was totally closed in 77.2% of group II and
      47.1% of group I (p < 0.01). In partial AVSDs, freedom from postoperative LAVV
      insufficiency was 77.0% in group II versus 30.5% in group I at 5 years (p =
      0.009) and freedom from reoperation was 89.9% in group II versus 58.3% in group I
      at 5 years (p = 0.012); however, there was no difference in complete AVSDs. None
      of the infants in group I underwent total cleft closure and 4 of them showed more
      than moderate LAVV insufficiency postoperatively. CONCLUSIONS: Double-orifice
      LAVV is a significant predictor for postoperative LAVV incompetence and
      reoperation in partial AVSDs, but not in complete AVSDs. Surgical procedures for
      the cleft should be individualized with careful intraoperative evaluation of the
      structure and function of this abnormal valve, especially in partial AVSDs and
      infants.

PMID- 11834067
TI  - Apico-aortic conduits in children with severe left ventricular outflow tract
      obstruction.
AB  - BACKGROUND: Infrequently, congenital heart defects are complicated by left
      ventricular outflow tract obstruction (LVOTO) not amenable to conventional
      reconstruction. Apico-aortic conduits provide a means of palliating such patients
      until definitive repair is possible. The purpose of this study was to review a
      single institution's current experience with apico-aortic conduits. METHODS: The
      medical records of pediatric patients receiving apico-aortic conduits were
      reviewed. Demographics, operative techniques, preoperative and postoperative
      physiologic variables, morbidity, mortality, and functional class were recorded.
      Off-pump and on-pump procedures were categorized for comparison. RESULTS: Ten
      cases of apico-aortic conduits for left ventricular outflow tract obstruction
      were identified. Indications included congenital aortic stenosis, aortic atresia,
      and subaortic stenosis. Six procedures were performed off-pump and four required
      median sternotomy with cardiopulmonary bypass as necessitated by concomitant
      procedures. There was one operative death. The remaining patients demonstrated
      hemodynamic improvements and are all alive to date. One patient required conduit
      valve replacement. All patients are in New York Heart Association classification
      I or II at the time of last follow-up. CONCLUSIONS: Apico-aortic conduits provide
      a safe and effective treatment alternative for select cases of left ventricular
      outflow tract obstruction. Off-pump techniques are feasible in the majority of
      cases. This valuable adjunct should be considered whenever conventional repair of
      left ventricular outflow tract obstruction is considered prohibitive.

PMID- 11834066
TI  - Total cavopulmonary connection with an extracardiac conduit: experience with 100
      patients.
AB  - BACKGROUND: In the Fontan procedures total cavopulmonary connection with an
      extracardiac conduit is a concern. The potential benefits of an extracardiac
      conduit may be the avoidance of postoperative supraventricular arrhythmias over
      the long-term, hemodynamic benefits due to laminar flow, possibility of
      completion without anoxic arrest, and applicability to anomalous systemic or
      pulmonary venous return, or both anomalous systemic and pulmonary venous return.
      We demonstrate early to midterm results of total cavopulmonary connection with an
      extracardiac conduit. METHODS: Between March 1994 and February 2000, a total of
      100 patients underwent total cavopulmonary connection with an extracardiac
      conduit. In 27 patients, who underwent a single stage total cavopulmonary
      connection operation, 7 were done without palliation. Seventy-three patients had
      undergone a bidirectional Glenn shunt before completion of the total
      cavopulmonary connection. We used an expanded polytetrafluoroethylene tube graft
      as the extracardiac conduit. RESULTS: Cardiopulmonary bypass time was 133.2+/
      55.2 minutes. Myocardial ischemic time was 38.5+/-23.2 minutes in 40 patients who
      needed cardioplegic cardiac arrest for intracardiac procedures. Intraoperative
      fenestration was done in only 1 patient. There were no operative deaths. During
      follow-up of 37.3 months, there were 5 late deaths. When compared with the
      patients treated by the lateral tunnel technique in our institute, there was no
      significant difference in actuarial survival rate, but the event free rate of the
      extracardiac conduit group was significantly superior to the lateral tunnel
      group. CONCLUSIONS: Total cavopulmonary connection with the extracardiac conduit
      produced good results in short to midterm follow-up.

PMID- 11834068
TI  - Successful late reintervention after the arterial switch procedure.
AB  - BACKGROUND: The arterial switch operation is the therapy of choice for
      transposition of the great arteries. METHODS: A retrospective analysis of all
      children undergoing the arterial switch operation between November 1985 and
      October 2000 was conducted, highlighting the frequency and nature of late
      invasive reintervention. RESULTS: One hundred forty-four children were operated
      on. Operative survival was 89% (128 of 144). Late reintervention was required in
      23% (29 of 128) of survivors. Neopulmonary stenosis (PS) was the most common
      complication requiring treatment, occurring in 16% (21 of 128) of patients.
      Eleven of 21 patients with PS required reoperation, whereas 10 were managed with
      percutaneous techniques. Other indications for reintervention included aortic
      arch obstruction (3 patients), ventricular septal defect (with PS in 2 patients),
      bronchial stenosis (2 patients), coronary stenosis (2 patients), aortic stenosis
      (with PS in 1 patient), and residual atrial septal defect (1 patient). There has
      been no mortality or major morbidity in those children who have undergone
      reintervention. CONCLUSIONS: Invasive reintervention after the arterial switch
      operation is occasionally required. The most common indication is PS.
      Reintervention is well tolerated by those children who require it. Continued
      follow-up for late complications is required in this patient population.

PMID- 11834069
TI  - How to diminish reoperation rates after initial repair of tetralogy of Fallot?
AB  - BACKGROUND: Complete correction of tetralogy of Fallot has good long-term
      results. Right ventricular outflow tract obstruction and pulmonary insufficiency
      occur which require reintervention. The present study evaluated the efficacy of
      reoperation following complete correction of tetralogy of Fallot, the sites of
      recurrences and impact of techniques used at first operation. METHODS: Between
      1980 and 1999, 501 patients underwent complete correction of tetralogy of Fallot.
      Reoperation rate was 7.4%. Residual or recurrent right ventricular outflow tract
      stenosis was seen in 25 patients (68%), and 7 patients (19%) had severe pulmonary
      insufficiency. Age at redo was 9.1+/-6.4 years. Restenosis was most frequently
      observed (75%) at the bifurcation of the pulmonary artery. Extended 1-patch
      enlargement was used until 1989 and thereafter changed to a 2-patch technique.
      RESULTS: Valvar-supravalvar 1-patch technique had a redo rate of 33.3%, compared
      with 4.3% for the 2-patch technique, p = 0.0264, with excellent freedom from
      reoperation rate. At reoperation right ventricular-pulmonary artery (RV-PA)
      conduits managed 29 patients and 3 had supravalvar patch enlargement. Hospital
      mortality was 5.4% (2 of 37). Twenty-five patients (68%) were in New York Heart
      Association functional class I to II at end of the follow-up, and none required
      further interventions. CONCLUSIONS: Redo rate following complete correction of
      tetralogy of Fallot was 7.4%. Right ventricular outflow tract pathology was the
      dominant reason for reoperations (86%). At reoperation, RV-PA conduits was the
      most frequently used technique. Reoperation was efficient in reducing the RV-PA
      gradient, had low hospital and late mortality. A 2-patch valvar-supravalvar
      enlargement at first operation reduced the risk for redo in long-term follow-up.

PMID- 11834070
TI  - Conference on Cardiac and Vascular Surgery: Neurobehavioral Assessment,
      Physiological Monitoring and Cerebral Protective Strategies. 2001 Outcomes, the
      Key West Meeting. May 23-27, 2001. Key West, Florida, USA. Proceedings and
      abstracts.

PMID- 11834072
TI  - Magnetic resonance imaging registration and quantitation of the brain before and
      after coronary artery bypass graft surgery.

PMID- 11834071
TI  - Assessing the learning curve in off-pump coronary artery surgery via CUSUM
      failure analysis.

PMID- 11834073
TI  - Method development and analysis of retail foods for annatto food colouring
      material.
AB  - Analytical methods for the determination of the permitted food colouring annatto
      (E160b) have been developed or refined to encompass the wide range of food
      commodity types permitted to contain it. Specific solvent extraction regimens
      have been used depending upon the food commodity analysed and HPLC analysis
      techniques coupled with spectral confirmation have been used for the
      determination of the major colouring components. Qualitative and quantitative
      data on the annatto content of 165 composite and two single retail food samples
      covering a wide range of foods at levels above the limit of quantification (0.1
      mg kg(-1)) is reported. Quantitative results are given for the major colour
      principals 9'-cis-bixin, 9'-cis-norbixin and trans-bixin. Semi-quantitative
      results are given for the minor bixin and norbixin isomers monocis- (not 9'-), di
      cis- and trans-norbixin, for which authentic reference standards were not
      available. Repeat analyses (n = 4-9) of 12 different types of food commodity
      (covering the permitted range) spiked with annatto at levels between 1.7 and 27.7
      mg kg(-1) gave mean recoveries between 61 and 96%. The corresponding relative SDs
      (RSD) were between 2.1 and 7.9%.

PMID- 11834074
TI  - Determination of residues of oxolinic acid and flumequine in freeze-dried salmon
      muscle and skin by HPLC with fluorescence detection.
AB  - A procedure for the determination of residues of oxolinic acid (OA) and
      flumequine (FLU) in freeze-dried salmon muscle with attached skin, using reversed
      phase high-performance liquid chromatography, is described. OA and FLU were
      extracted by a solid-liquid extraction procedure: after addition of hydrochloric
      acid, extraction used successively ethyl acetate, sodium hydroxide and
      chloroform. Liquid chromatography was performed on a 5 microm PuroSpher RP-18E
      cartridge using acetonitrile and 0.02 M aqueous orthophosphoric acid solution as
      mobile phase, with fluorescence detection. The performance of the method was
      established by spiking tissues with OA and FLU before the freeze-drying step. The
      method was linear over the concentration range 50-2000 ng/g freeze-dried tissue.
      Limits of detection and quantitation were 3.2 and 16 ng/g wet weight tissue
      respectively both for OA and FLU. Mean extraction recoveries of OA and FLU from
      freeze-dried tissue were 85.5 and 85.2% respectively. The method is suitable as a
      regulatory one for determination of residues of OA and FLU in freeze-dried salmon
      tissue.

PMID- 11834075
TI  - Analysis of erythromycin and oleandomycin residues in food by high-performance
      liquid chromatography with fluorometric detection.
AB  - A reliable and sensitive procedure is presented for the analysis of erythromycin
      (ERY) and oleandomycin (OLE) in food of animal origin, such as meat, liver,
      kidney, raw milk and egg. The method is based on a solid-phase extraction clean
      up with a cation exchange cartridge, a 9-fluoromethylchloroformate (FMOC)
      precolumn derivatization and a separation by HPLC with fluorometric detection.
      The selectivity is satisfactory enough to control ERY and OLE residues as not
      many interfering peaks are observed for various food matrices. The macrolides
      recoveries of the total procedure were low, although >50%. However, addition of
      an internal standard (roxithromycin) corrected for recovery to give satisfactory
      quantitative results for repeatability, linearity, detection and quantification
      limits and mainly accuracy.

PMID- 11834076
TI  - Lead content in Spanish market infant formulas and toxicological contribution.
AB  - Lead content was investigated in infant formulas by using graphite furnace atomic
      absorption spectroscopy (GFAAS). Formulas were distinguished as 'beginner',
      'continuation' and 'special infant formula', the latter being classified as
      subtypes 'hypoallergenic', 'without lactose', 'vegetable base' and 'others'. The
      mean concentrations of lead were 25.7+/-8.4, 36.9+/-6.4 and 43.5+/-16.3 microg
      kg(-1) for beginner, continuation and special infant formula, respectively. Two
      factor (types and subtypes) variance analyses were made and Tukey's mean
      homogeneity test (p < 0.05) was also performed for the formation of homogeneous
      groups. Significant differences (p < 0.001) were observed between types and two
      homogeneous groups were formed by the special infant formula type, with the
      highest lead content; the other group was constituted by the beginner type; and
      included in both groups were the continuation type infant formula. Their
      contribution to the provisional weekly intake (PTWI) was calculated from the mean
      concentrations in each type of infant formula, showing them to be food with a low
      toxicological risk (< 30% PTWI).

PMID- 11834077
TI  - Comparison of extraction and clean-up procedures for analysis of zearalenone in
      corn, rice and wheat grains by high-performance liquid chromatography with
      photodiode array and fluorescence detection.
AB  - The aim of this work was the optimization of some procedures usually used in the
      analysis of zearalenone (ZEA) in corn and other cereals by high-performance
      liquid chromatography (HPLC) with photodiode array and/or fluorescence detection.
      The comparison of five extraction solvents is presented. Three solid-phase
      extraction cartridges (C-18, silica, Florisil) and immuno-affinity columns were
      also compared to obtain the best recovery of the mycotoxin with the minimal
      presence of co-extractives in the chromatograms. Mixtures of methanol-1% aqueous
      NaCl (80.20 or 60:40 v/v) were the best extraction solvents. Florisil provided
      higher recovery of ZEA than C-18, and silica proved unsuitable. The immuno
      affinity column was very efficient in cleaning the extracts, but its sample
      capacity was lower than that of SPE columns due to saturation. The mobile phase
      (methanol-water 80:20 v/v) gave a low retention time for ZEA (approximately 5
      min), high sensitivity and acceptable separation between this mycotoxin and alpha
      zearalenol. The optimized protocol is straightforward, provides high ZEA
      recoveries in spiked corn (mean 102.4%), has an acceptable sensitivity and has a
      lack of interference with fluorescence detection (detection limit 4 ng ZEA g(-1)
      corn). The photodiode array detector was useful, except at very low ZEA levels,
      to confirm the identity of the mycotoxin. The method was applied to search for
      ZEA accumulation in corn, wheat and rice grains inoculated with selected strains
      of Fusarium graminearum, F. oxysporum and method was applied to search for ZEA
      accumulation in corn, wheat and rice grains inoculated with selected strains of
      Fusarium graminearum, F. oxysporum and F. culmorum.

PMID- 11834078
TI  - Balkan endemic nephropathy and associated urinary tract tumours: a review on
      aetiological causes and the potential role of mycotoxins.
AB  - A series of publications in the 1950s described a kidney disease in Bulgaria, the
      former Yugoslavia and Romania that became known as Balkan endemic nephropathy
      (BEN). The disease was qualified by World Health Organisation (WHO) experts as
      'progressive and very gradually developing renal failure with insidious onset....
      The last stage shows marked fibrosis...'. BEN is characterized by tubular
      degeneration, interstitial fibrosis and hyalinization of glomeruli accompanied by
      enzymuria and impaired renal function without nephrotic syndrome. Later, an
      association between BEN and tumours of the kidney pelvis and ureter was
      recognized, so that the problem of BEN became not only nephrological, but also
      oncological. There may also be an association with increased urinary bladder
      cancer incidence, although many confounding factors may interfere in the analysis
      of data for this organ. In view of the very intimate association between BEN and
      the urinary tract tumours (UTT), the term 'endemic uropathy' has been proposed.
      Several hypothesis concerning the aetiology of these diseases has been
      investigated, which include: predisposing genes factors, environmental factors
      (heavy metals, minerals, bacteria, leptospira, viruses, fungal toxins and, most
      recently, pliocene lignites). This paper reviews the different hypotheses about
      the aetiology of endemic uropathy and pays particular attention to the role of
      fungal toxins.

PMID- 11834079
TI  - Shelf life extension of pre-baked buns by an ACTIVE PACKAGING ethanol emitter.
AB  - The paper reports the influence of an ethanol emitter (Ethicap) on the
      microbiological condition and the shelf life extension of a bakery product. Pre
      baked buns, with a water activity of 0.95, were packaged with different amounts
      of Ethicap and stored at room temperature. Yeasts and moulds remained largely
      absent from the core of the pre-baked bun (< 10(2) cfu g(-1)) during storage,
      independent of the presence of ethanol. The total mesophilic count was low at the
      beginning of the storage experiment (< 10(2) cfu g(-1)), but increased without
      ethanol within 1 week to an unacceptable level. In the presence of ethanol, the
      total mesophilic count stabilizes at a consumable level of 10(5)-10(6) cfu g(-1).
      The increase of total mesophilic count was caused by growth of a Bacillus spp.,
      probably B. subtilis. Mould growth on the outer surface is limiting for shelf
      life extension. On the pre-baked buns, the following moulds were present:
      Penicillium solitum, P. commune, P. corylophilum, Cladosporium sphaerospermum and
      C. herbarum. These started to grow within 4-6 days. Mould growth can be delayed
      for 13 days by adding Ethicap. The ethanol probably has to be absorbed by the pre
      baked bun to be effective in growth suppression of the Bacillus spp. the moulds.
      The pre-baked buns absorb most of the ethanol from the package headspace, and the
      ethanol content of the products is approximately 0.8 weight% after 21 days. This
      largely exceeds the overall migration limit of 60 mg kg(-1) food (0.006 weight%).

PMID- 11834081
TI  - Plasma kinetics of a cholesterol-rich emulsion in young, middle-aged, and elderly
      subjects.
AB  - Low density lipoprotein (LDL) plasma concentration is increased in the elderly.
      In this group, the incidence of coronary artery disease (CAD) is greater and LDL
      remains an important risk factor for CAD development. In this study, the plasma
      kinetics of a cholesterol-rich emulsion that binds to LDL receptors was studied
      in 10-subject groups of the elderly (70 +/- 4 yr), middle-aged (42 +/- 5 yr) and
      young (23 +/- 2 yr). All were normolipidemic, nonobese, nondiabetic subjects who
      did not have CAD. The emulsion was labeled with 14C-cholesteryl oleate and
      injected intravenously into the subjects. Blood samples were drawn at regular
      intervals over 24 h to determine the plasma decay curve of the emulsion
      radioactive label and to estimate its plasma fractional clearance rate (FCR, in
      h(-1)). FCR of the emulsion label was smaller in elderly compared to young
      subjects (0.032 +/- 0.035 and 0.071 +/- 0.049 h(-1), respectively; mean +/- SD,
      P< 0.05). FCR of the middle-aged subjects (0.050 +/- 0.071 h(-1)) was
      intermediate between the values of the elderly and young subjects, although not
      statistically different from them. A negative correlation was found betweeen the
      emulsion FCR and subjects' age (r = -0.47, P = 0.008). We conclude that aging is
      accompanied by progressively diminished clearance of the emulsion cholesterol
      esters and, by analogy, of the native LDL.

PMID- 11834082
TI  - Incorporation of alpha-tocopherol in marine lipid-based liposomes: in vitro and
      in vivo studies.
AB  - Liposomes made from a natural marine lipid extract and containing a high
      polyunsaturated n-3 fatty lipid ratio were envisaged as oral route vectors and a
      potential alpha-tocopherol supplement. The behavior of vesicles obtained by
      simple filtration and of giant vesicles prepared by electroformation was
      investigated in gastrointestinal-like conditions. The influence of alpha
      tocopherol incorporation into liposomes was studied on both physical and chemical
      membrane stability. Propanal, as an oxidation product of n-3 polyunsaturated
      fatty acids, was quantified by static headspace gas chromatography when alpha
      tocopherol incorporation into liposome ratios ranged from 0.01 to 12 mol%. Best
      oxidative stability was obtained for liposomes that contained 5 mol% alpha
      tocopherol. Compared to the other formulas, propanal formation was reduced, and
      time of the oxidation induction phase was longer. Moreover, alpha-tocopherol
      induced both liposome structural modifications, evidenced by turbidity, and
      phospholipid chemical hydrolysis, quantified as the amount of lysophospholipids.
      This physicochemical liposome instability was even more pronounced in acid
      storage conditions, i.e., alpha-tocopherol incorporation into liposome membranes
      accelerated the structural rearrangements and increased the rate of phospholipid
      hydrolysis. In particular, giant vesicles incubated at pH 1.5 underwent complex
      irreversible shape transformations including invaginations. In parallel, the
      absorption rate of alpha-tocopherol was measured in lymph-cannulated rats when
      alpha-tocopherol was administrated, as liposome suspension or added to sardine
      oil, through a gastrostomy tube. Alpha-tocopherol recovery in lymph was increased
      by almost threefold, following liposome administration. This may be related to
      phospholipids that should favor alpha-tocopherol solubilization and to liposome
      instability in the case of a high amount of alpha-tocopherol in the membranes. A
      need to correlate results obtained from in vitro liposome behavior with in vivo
      lipid absorption was demonstrated by this study.

PMID- 11834083
TI  - Novel vitamin E derivative with 4-substituted resorcinol moiety has both
      antioxidant and tyrosinase inhibitory properties.
AB  - A novel vitamin E derivative, (6"-hydroxy-2",5",7",8"-tetramethylchroman-2"
      yl)methyl 3-(2',4'-dihydroxyphenyl)propionate (TM4R), which has a chromanoxyl
      ring and 4-substituted resorcinol moieties, was synthesized; and its inhibitory
      effects on tyrosinase, antioxidant ability, and lightening effect of ultraviolet
      B (UVB)-induced hyperpigmentation were estimated. TM4R showed potent inhibitory
      activity on tyrosinase, which is the rate-limiting enzyme in melanogenesis. The
      scavenging activities of TM4R on 1,1-diphenyl-2-picrylhydrazyl and hydroxyl
      radicals were found to be nearly the same as those of alpha-tocopherol.
      Furthermore, an efficient lightening effect was observed following topical
      application of TM4R to UVB-stimulated hyperpigmented dorsal skin of brownish
      guinea pigs. These results suggest that TM4R may be a candidate for an efficient
      whitening agent, possibly by inhibiting tyrosinase activity and biological
      reactions caused by reactive oxygen species.

PMID- 11834080
TI  - Factors affecting the storage and excretion of toxic lipophilic xenobiotics.
AB  - Lipophilic toxins have been introduced into the environment both as functional
      compounds, such as pesticides, and as industrial waste from incineration or the
      manufacture of electrical transformer components. Among these substances are
      compounds that are carcinogenic and that affect the endocrine system. Accidental
      high exposures of humans to some lipophilic toxins have produced overt disease
      symptoms including chloracne and altered liver function. These toxic materials
      have been the recent focus of international effort to reduce or eliminate classes
      of halogenated hydrocarbons from the environment. Evidence of the widespread
      distribution of lipophilic toxins in the biosphere has been obtained by analyses
      of human tissues and human milk. The principal route of entry of lipophilic
      toxins into humans is through the food chain, and most of them are stored in
      adipose tissue. A common route of excretion is in bile, but there is also
      evidence of nonbiliary excretion into the intestine. Enterohepatic circulation of
      many of these compounds slows their removal from the body. Substances that
      interrupt the enterohepatic circulation of compounds that enter the intestine by
      the biliary and nonbiliary routes increase the rate of their removal from the
      body and reduce their storage half-lives. Reduction in body fat, along with these
      dietary substances that interrupt enterohepatic circulation, further enhances the
      excretion rate. Areas for further research include optimizing regimens for body
      burden reductions, understanding the nature of nonbiliary excretion, and
      following the effects of tissue redistribution during loss of body fat.

PMID- 11834084
TI  - Beta-oxidation of conjugated linoleic acid isomers and linoleic acid in rats.
AB  - To assess the oxidative metabolism of conjugated linoleic acid (CLA) isomers,
      rats were force-fed 1.5-2.6 MBq of [1-14C]-linoleic acid (9c,12c-18:2), -rumenic
      acid (9c,11t-18:2), or-10trans,12cis-18:2 (10t,12c-18:2), and 14CO2 production
      was monitored for 24 h. The animals were then necropsied and the radioactivity
      determined in different tissues. Both CLA isomers were oxidized significantly
      more than linoleic acid. Moreover, less radioactivity was recovered in most
      tissues after CLA intake than after linoleic acid intake. The substantial
      oxidation of CLA isomers must be considered when assessing the putative health
      benefits of CLA supplements.

PMID- 11834085
TI  - Dietary alpha-linolenic acid lowers postprandial lipid levels with increase of
      eicosapentaenoic and docosahexaenoic acid contents in rat hepatic membrane.
AB  - This study was designed to examine the effects of dietary n-3 and n-6
      polyunsaturated fatty acids (PUFA) on postprandial lipid levels and fatty acid
      composition of hepatic membranes. Male Sprague-Dawley rats were trained for a 3-h
      feeding protocol and fed one of five semipurified diets: one fat-free diet or one
      of four diets supplemented with 10% (by weight) each of corn oil, beef tallow,
      perilla oil, and fish oil. Two separate experiments were performed, 4-wk long
      term and 4-d short-term feeding models, to compare the effects of feeding
      periods. Postprandial plasma lipid was affected by dietary fats. Triacylglycerol
      (TG) and total cholesterol levels were decreased in rats fed perilla oil and fish
      oil diets compared with corn oil and beef tallow diets. Hepatic TG and total
      cholesterol levels were also reduced by fish oil and perilla oil diets. Fatty
      acid composition of hepatic microsomal fraction reflected dietary fatty acids and
      their metabolic conversion. The major fatty acids of rats fed the beef tallow
      diet were palmitic, stearic, and oleic. Similarly, linoleic acid (LA) and
      arachidonic acid in the corn oil group, alpha-linolenic acid (ALA) and
      eicosapentaenoic acid (EPA) in the perilla oil group, and palmitic acid and
      docosahexaenoic acid (DHA) in the fish oil group were detected in high
      proportions. Both long- and short-term feeding experiments showed similar
      results. In addition, microsomal DHA content was negatively correlated with
      plasma lipid levels. Hepatic lipid levels were also negatively correlated with
      EPA and DHA contents. These results suggest that n-3 ALA has more of a
      hypolipidemic effect than n-6 LA and that the hypolipidemic effect of n-3 PUFA
      may be partly related to the increase of EPA and DHA in hepatic membrane.

PMID- 11834087
TI  - Analysis of molecular species of peroxide adducts of triacylglycerols following
      treatment of corn oil with tert-butyl hydroperoxide.
AB  - We recently demonstrated that exposure of synthetic mono- and diunsaturated
      triacylglycerols to tert-butylhydroperoxide (TBHP) leads to formation of stable
      adducts of the oxidizing agent and the unsaturated esters (Sjovall, O., Kuksis,
      A., and Kallio, H., Reversed Phase High-Performance Liquid Chromatographic
      Separation of tert-Butyl Hydroperoxide Oxidation Products of Unsaturated
      Triacylglycerols, J. Chromatogr. A 905, 119-132, 2001). In the present study we
      isolated and identified the TBHP adducts of corn oil triacylglycerols. The much
      wider range of molecular species available in the corn oil permitted us to
      demonstrate that the yield of the adducts varies with the degree of unsaturation
      of the triacylglycerol. The highest yields were obtained for the linoleate (20%,
      of linoleoyl-containing residual triacylglycerols) and the lowest ones for the
      oleate (5% of oleoyl-containing residual triacylglycerols) triacylglycerols,
      whereas the saturated triacylglycerols did not give TBHP adducts in readily
      detectable amounts. Normal-phase thin-layer chromatography along with reversed
      phase high-performance liquid chromatography/mass spectrometry (LC/MS) with
      electrospray ionization was used to isolate and separate the major molecular
      species of polyunsaturated triacylglycerols and corresponding TBHP adducts. As an
      extreme example, the dilinoleoylmonooleoylglycerol was identified as the mono-,
      di-, tri-, tetra-, and penta-TBHP adduct. LC/MS with electrospray ionization at
      elevated capillary exit voltage (pseudo tandem mass spectrometry) was used to
      confirm structures of the [M-RCOOH]+ ions and the absence of TBHP adducts of [M
      RCOOH]+. It is concluded that stable adduct formation is an unavoidable
      complication of preparation of oxotriacylglycerols by oxidation with concentrated
      TBHP solutions and care must be taken to resolve the adducts from the desired
      oxidation product.

PMID- 11834086
TI  - Effect of dexamethasone on the fatty acid composition of total liver microsomal
      lipids and phosphatidylcholine molecular species.
AB  - Dexamethasone depresses delta6 and delta5 and increases delta9 desaturase and
      synthase activities. Therefore, we investigated the effect on the fatty acid
      composition of microsomal liver lipids and phosphatidylcholine (PtdCho) molecular
      species. After 15 d of treatment we found a notable decrease in arachidonic acid,
      a small decrease in stearic acid, and increases of linoleic, oleic, palmitoleic,
      and palmitic acids in liver microsomal total lipids and PtdCho. The study of the
      distribution of the PtdCho molecular species indicated that 18:0/20:4n-6,
      16:0/20:4n-6, and 16:0/18:2n-6 predominated in the control animals.
      Dexamethasone, as expected because of its depressing effect on arachidonic acid
      synthesis and activation of oleic and palmitic acid synthesis, evoked a very
      significant decrease in 18:0/20:4n-6 PtdCho (P<0.001) and an important increase
      in 16:0/18:2n-6. The invariability of 16:0/20:4n-6 PtdCho could be related to the
      antagonistic effect of arachidonic and palmitic acid synthesis. PtdCho species
      containing oleic acid were not significant. The bulk fluidity and dynamic
      properties of the microsomal lipid bilayer measured by fluorometry using the
      probes 1,6-diphenyl-1,3,5-hexatriene and 4-trimethylammonium-phenyl-6-phenyl
      1,3,5-hexatriene showed no significant modification, probably owing to a
      compensatory effect of the different molecular species, but changes of particular
      domains not detected by this technique are possible. However, the extremely
      sensitive Laurdan detected increased lipid packing in the less-fluid domains of
      the polar-nonpolar interphase of the bilayer, possibly evoked by the change of
      molecular species and cholesterol/phospholipid ratio. The most important effect
      found is the decrease of arachidonic acid pools in liver phospholipids as one of
      the corresponding causes of dexamethasone-dependent pharmacological effects.

PMID- 11834088
TI  - Sterol biosynthesis by the arbuscular mycorrhizal fungus Glomus intraradices.
AB  - Ri-T-DNA-transformed carrot roots were used for investigating sterol metabolism
      by the arbuscular mycorrhizal (AM) fungus Glomus intraradices under three
      distinct experimental conditions: (i) a symbiotic stage (fungus still attached to
      the host roots); (ii) a detached stage (fungus physically separated from the
      roots); and (iii) a germinating stage (germinating spores). In all three stages,
      G. intraradices was found to contain a mixture of 24-alkylated sterols, with 24
      methyl and 24-ethyl cholesterol as the main compounds, but no ergosterol, the
      predominant sterol in most fungi. Feeding experiments with [1-14C]sodium acetate
      were performed to check the ability of the fungus to synthesize sterols. Whatever
      the experimental conditions, G. intraradices was able to actively take up
      exogenous acetate and to incorporate it into sterols and their precursors. Our
      data provide first evidence for de novo sterol synthesis by an AM fungus.

PMID- 11834089
TI  - A new trihydroxy fatty acid from the ascomycete, Chinese truffle Tuber indicum.
AB  - From the chloroform/methanol extract of the fruiting bodies of the ascomycete
      Chinese truffle Tuber indicum Cooke et Massee, a new trihydroxylated
      monounsaturated fatty acid (1) has been isolated. The structure of this new
      linoleic acid-derived metabolite was established as 9,10,11-trihydroxy-(12Z)-12
      octadecenoic acid by means of spectroscopic and chemical methods. The fatty acid
      composition of the chloroform-soluble fraction of this fungus was analyzed by gas
      chromatography-mass spectrometry. The content of the predominant unsaturated
      fatty acids (oleic and linoleic acids) is as high as 68%. The use of dimethyl
      disulfide adduct was effective in the determination of the position of the double
      bond, and the glycol oxidation fission reaction with sodium metaperiodate
      supported on silica gel was helpful in establishing the location of the
      trihydroxylic groups in the new fatty acid.

PMID- 11834090
TI  - Identification of novel nonmethylene-interrupted fatty acids, 7E,13E-20:2,
      7E,13E,17Z-20:3, 9E,15E,19Z-22:3, and 4Z,9E,15E,19Z-22:4, in Ophiuroidea (brittle
      star) lipids.
AB  - Fatty acids of Ophiuroidea (brittle star) Ophiura sarsi have been investigated by
      gas-liquid chromatography (GLC). About 2-13% of four unidentified fatty acids
      were found in total fatty acids from a sample caught at a depth of 1,100 m.
      Structural analyses were undertaken after partial hydrogenation of their
      concentrates with hydrazine hydrate and subsequent isolation of the monoenoate
      products by argentation thin-layer chromatography. The structures of the
      unidentified fatty acids were determined as 7E,13E-eicosadienoic (20:2),
      7E,13E,17Z-eicosatrienoic (20:3), 9E,15E,19Z-docosatrienoic (22:3), and
      4Z,9E,15E,19Z-docosatetraenoic (22:4) acids by gas chromatography-mass
      spectrometry of dimethyl disulfide adducts and GLC of the monoenoates on a polar
      column. These fatty acids belong to a family of nonmethylene-interrupted (NMI)
      polyunsaturated fatty acids frequently observed in marine invertebrates and
      conifer seeds. As far as the authors know, however, these NMI fatty acid types
      with mixed geometry of ethylenic bonds have not been reported previously.

PMID- 11834091
TI  - Regioisomers of octanoic acid-containing structured triacylglycerols analyzed by
      tandem mass spectrometry using ammonia negative ion chemical ionization.
AB  - Tandem mass spectrometry based on ammonia negative ion chemical ionization and
      sample introduction via direct exposure probe was applied to analysis of
      regioisomeric structures of octanoic acid containing structured triacylglycerols
      (TAG) of type MML, MLM, MLL, and LML (M, medium-chain fatty acid; L, long-chain
      fatty acid). Collision-induced dissociation of deprotonated parent TAG with argon
      was used to produce daughter ion spectra with appropriate fragmentation patterns
      for structure determination. Fatty acids constituting the TAG molecule were
      identified according to [RCO2]- ions in the daughter ion spectra. With the
      standard curve for ratios of [M-H-RCO2H-100]- ions corresponding to each [RCO2]-
      ion, determined with known mixtures of sn-1/3 and sn-2 regioisomers of structured
      TAG, it was possible to determine the proportions of different regioisomers in
      unknown samples. The method enabled quantification of MML- and MLM-type
      structured TAG. In the case of MLL- and LML-type TAG, it was possible to
      determine the most abundant regioisomer in the unknown mixture and estimate the
      proportions of regioisomers when there were more than 50% MLL-type isomers in the
      mixture.

PMID- 11834092
TI  - Dehydroepiandrosterone alters phospholipid profiles in Zucker rat muscle tissue.
AB  - Insulin-resistant muscle tissue contains low proportions of arachidonic acid
      (AA), and increased proportions of muscle AA correlate with improved insulin
      sensitivity. Dehydroepiandrosterone (DHEA) and AA, like the thiazolidinedione
      drugs that decrease insulin resistance (IR), are peroxisome proliferators. Long
      chain fatty acids (FA) have been named the "one true" endogenous ligand for
      activating the peroxisome proliferator-activator receptor (PPAR), and DHEA has
      been named a "good candidate" as a naturally occurring indirect activator of
      PPAR. This study was conducted to determine DHEA's effects on lipid profiles of
      skeletal and cardiac muscle in lean and obese Zucker rats (ZR), a model of IR,
      type 2 diabetes mellitus, and obesity. We hypothesize that DHEA may alter long
      chain FA profiles in muscle tissue of obese rats such that they more closely
      resemble that of the lean. In our experiments, we employed a DHEA and a pair-fed
      (PF) group (n = 6) for 12 lean and 12 obese ZR. For 30 d, the diet of the two
      DHEA groups was supplemented with 0.6% DHEA; PF groups were given the average
      daily calories consumed by their corresponding treatment group. Hearts and
      gastrocnemius muscles were assayed for phospholipid (PL), free FA, and
      triglyceride (TG) FA profiles. The proportion of PL AA was significantly greater
      in both muscle types of lean compared to obese rats. Hearts from both DHEA groups
      had greater PL proportions of AA and less oleic (18:1) acid than their PF
      controls. Likewise, 18:1 proportions were significantly lower in the
      gastrocnemius; however, AA proportions were not significantly different. Similar
      phenotypic profile differences were observed in the TG fraction of both muscle
      types. There were no DHEA-related TG FA profile alterations.

PMID- 11834093
TI  - Chromatographic methods for ceramide identification.

PMID- 11834094
TI  - Factors associated with the temporomandibular disorder, pain dysfunction syndrome
      (PDS): Manchester case-control study.
AB  - OBJECTIVES: To determine the individual and combined effects of potential risk
      factors in relation to the temporomandibular disorder, Pain Dysfunction Syndrome
      (PDS). DESIGN: Case-control study. MATERIAL AND METHODS: Cases were new referrals
      to the temporomandibular disorder clinic of the University Dental Hospital of
      Manchester, diagnosed with PDS. Controls were randomly selected from 24 dental
      practices. Using a postal questionnaire information was collected on socio
      demographic, local mechanical, psychological factors, co-morbidities and illness
      behaviour. The adjusted participation rate was similar in cases and controls
      (64%), and 131 cases and 196 controls finally participated in the study. RESULTS:
      Compared with the controls, the cases were more likely to report that their teeth
      felt as though they did not fit together properly [odds ratio (OR) 8, 95%
      Confidence Interval (CI) 6-13] and report history of facial trauma (OR 3, 95% CI
      2-6). Both diurnal and nocturnal grinding were significantly associated with PDS,
      and individuals who reported grinding their teeth both during the day and at
      night had a risk of 6; 95% CI 3-13 for PDS compared with those who did not. A
      history of orthodontic treatment, having any dentures, having missing teeth, use
      of chewing gum or biting the fingernails did not show any relationship with PDS.
      People who took medication for the bowels had a higher risk of PDS (OR 2, 95% CI
      1-4). Participants with frequent headaches had a threefold increase in risk of
      having PDS (OR 3, 95% CI 2-5) while having pain in parts of the body other than
      the head was associated with an OR of 3 (95% CI 2-5). An increased propensity to
      have PDS was seen in those individuals with higher levels of psychological
      distress (OR 3; 95% CI 1-4 in the highest category, test for trend P < 0.001) and
      sleep disturbance (OR 5; 95% CI 2-94 in the highest category, test for trend P <
      0.001). Aspects of illness behaviour, such as disease conviction (OR 4; 95% CI 2
      9 in the highest category) and perception of illness (0.3; 95% CI 0.2-0.5) were
      associated with PDS. The result for the denial scale became statistically
      significant after adjustment for age and gender (2; 95% CI 1-3). CONCLUSIONS: The
      current case-control study provides complementary epidemiological information on
      oro-facial pain (OFP) and supports a multifactorial aetiology of PDS, with
      factors from many domains, including local mechanical factors, psychological and
      co-morbidities. People with PDS were characterized by frequent headaches, history
      of facial trauma, teeth grinding, sleep problems, pain elsewhere in the body and
      high levels of psychological distress. From the results of current study and
      available evidence it seems inappropriate to consider PDS in isolation and future
      research should adopt a multidisciplinary approach to OFP.

PMID- 11834095
TI  - A novel point mutation (C571T) in the tissue-non-specific alkaline phosphatase
      gene in a case of adult-type hypophosphatasia.
AB  - OBJECTIVE: Hypophosphatasia (HOPS) is an inheritable disorder characterized by
      defective skeletal mineralization, deficiency of tissue-non-specific alkaline
      phosphatase (TNSALP) activity and premature loss of deciduous teeth. The gene for
      TNSALP is located on chromosome 1p34-36.1 and consists of 12 exons and 11
      introns. In this study we analysed the genomic TNSALP gene from a patient with
      HOPS, her family, and unrelated normal controls. MATERIALS AND METHODS: The
      proband was a 52-year-old Japanese woman with adult onset HOPS. The patient
      showed deficiency in alkaline phosphatase (ALP) activity, increased urinary
      excretion of phosphoethanolamine and severe periodontal disease. Genomic DNA was
      extracted from the peripheral leukocytes of the subjects. Based on published
      sequence data in the TNSALP gene, 11 pairs of polymerase chain reaction (PCR)
      primers were used to amplify the coding exons. The PCR amplified samples were
      subjected to PCR-single strand conformation polymorphism (SSCP) analysis and PCR
      allele specific oligonucleotide (ASO) analysis. RESULTS: By PCR-SSCP analysis of
      the patient's genomic DNA, fragments containing exon 5 revealed abnormal
      mobility. This abnormal mobility (exon 5) was also found in the genomic DNA in
      her mother's sister, but were not detected in her father, brothers or sisters,
      and unrelated normal controls. Sequencing analysis of the abnormal band extracted
      from the SSCP gel revealed a C to T transition at nucleotide position 571 (C571T)
      in exon 5. This mutation resulted in a substitution of Ala-115 with a Val in the
      mature TNSALP polypeptide. PCR-ASO analysis also confirmed this missense point
      mutation. The result of this study showed that the pro-band has inherited the
      C571T mutation in exon 5 from her mother alone and the disease in this family was
      inherited as an autosomal dominant trait from the pedigree. CONCLUSIONS: The
      C571T mutation is a new missense point mutation and appears to cause significant
      changes in the structure and function of TNSALP because Ala-115 is highly
      conserved in rat TNSALP and human tissue-non-specific, intestinal and placental
      ALPs.

PMID- 11834096
TI  - Immunohistochemical analysis of CD1a-labeled Langerhans cells in human dental
      periapical inflammatory lesions--correlation with inflammatory cells and
      epithelial cells.
AB  - OBJECTIVE: Distribution and density of CD1a-labeled Langerhans cells (LCs) were
      examined in human dental periapical inflammatory lesions, and compared with
      inflammatory cell infiltration or epithelial cell proliferation. MATERIALS AND
      METHODS: Eighty three periapical lesions (26 apical granulomas (AGs), 8
      epitheliated granulomas (EGs), 34 radicular cysts (RCs), 15 residual radicular
      cysts (RRCs)) were collected. As control, specimens of periodontal ligaments
      including Malassez epithelial rests were curetted from 21 teeth. LC densities
      were measured and various degrees of inflammatory cell infiltration were examined
      immunohistochemically. Labeling indices for the cellular proliferation markers Ki
      67 antigen and DNA topoisomerase II alpha were calculated in the epithelial
      components. RESULTS: LCs were found in all periapical lesions but not in Malassez
      epithelial rests. LCs were more abundant in epithelial components than in
      subepithelial layers. Intraepithelial LCs were more frequent in RCs than in RRCs,
      whereas subepithelial LCs were less frequent in RRCs than in AGs and EGs. T
      lymphocytes consistently outnumbered macrophages, plasma cells and B lymphocytes.
      The range of the CD4/CD8-positive cell ratio differed according to the lesions.
      Increased LC density was associated with the severity of CD3-positive cell
      infiltration. Ki-67- and Topo II-LI showed various degrees of epithelial
      immunoreactivity. There was a significant correlation between LC density and
      proliferative potential of the epithelium in periapical lesions. CONCLUSION:
      These findings suggested that LCs appeared to be associated with T lymphocyte
      infiltration and proliferative potential of the epithelial tissue in periapical
      lesions.

PMID- 11834097
TI  - Identification of the AgNORs, PCNA and ck16 proteins in oral lichen planus
      lesions.
AB  - The expression of proliferating cell nuclear antigen (PCNA), cytokeratin 16
      (ck16) and Ag nucleolar organizer regions (AgNORs) were assessed in 20 cases of
      lichen planus, 20 cases of keratosis and 20 cases of normal oral mucosa in order
      to evaluate the rate of keratinocyte proliferation in these tissues. Three
      hundred cells were counted in each sample: 100 basal cells, 100 suprabasal cells
      and 100 squamous cells. The mean number of AgNORs and the percentage of PCNA
      positive cells were calculated. Except from similar staining of suprabasal cells
      of lichen planus and keratosis, PCNA and AgNORs values were higher in all layers
      of lichen planus than in both keratosis and normal oral mucosa. The three groups
      showed similar ck16 immunostaining: all of the cells were positive, except those
      of the basal layer. The results suggest that the keratinocyte proliferation index
      is higher in lichen planus than in keratosis and normal mucosa. Besides, ck16
      should not be used to differentiate the entities studied.

PMID- 11834098
TI  - Short-term exposure to alcohol increases the permeability of human oral mucosa.
AB  - OBJECTIVES: The aim of this study was to evaluate the effect of short-term
      exposure to ethanol on the permeability barrier properties of human oral mucosa.
      MATERIALS AND METHODS: Permeability constants (Kp x 10(-4) cm min(-1)) to
      tritiated water were determined, for untreated human ventral tongue, and
      following treatment with phosphate-buffered saline (PBS), 5, 15 or 40% ethanol
      using an in vitro perfusion chamber system. Some samples were also exposed to
      fluorescent-labelled albumin and examined by fluorescence microscopy.
      Permeability barrier lipid composition was assessed in treated and untreated
      mucosa by heat separation, solvent extraction and thin layer chromatography.
      RESULTS: Fifteen per cent ethanol significantly increased mucosal permeability
      (5.8 +/- 0.44; P < 0.05) compared with untreated, PBS and 5% ethanol treated
      mucosa (4.69 +/- 0.26, 4.48 +/- 0.3 and 4.13 +/- 0.27, respectively). Albumin was
      restricted to the epithelial surface in control tissue, but extended further
      through the epithelium and, in some cases, into the connective tissue after
      treatment with ethanol. Biochemical analysis revealed no significant difference
      in the epithelial lipid composition of treated and untreated mucosa. CONCLUSIONS:
      These results suggest that short-term exposure to ethanol may act as a
      permeability enhancer, possibly by causing molecular rearrangement of the
      permeability barrier, not as a result of lipid extraction.

PMID- 11834099
TI  - Herbert A. deVries: 60 years of exercise and science.

PMID- 11834100
TI  - Effects of increased eccentric loading on bench press 1RM.
AB  - The purpose of this study was to measure the effects of additional eccentric
      loading on subsequent concentric strength. Eight subjects with some experience in
      weight training volunteered to perform maximal attempts in the barbell bench
      press using detaching hooks that allowed them to lower 105% of their concentric 1
      repetition maximum (RM) and raise 100%. The detaching hooks allowed attachment of
      extra weight to the bar and would release from the bar at the bottom of the lift,
      reducing the weight lifted during the concentric phase of the lift. After
      determining their 1RM for the bench press, the subjects attempted to increase
      their performance by using a heavier eccentric load with the detaching hooks. All
      8 subjects who completed the study increased their 1RMs by 5 to 15 pounds. The
      use of additional eccentric loading significantly (p = 0.008) increased the
      weight that could be lifted on the subsequent concentric phase and therefore 1RM
      performance. This phenomenon was a result of the enhancement of stretch
      shortening cycle performance by the increased eccentric load. Athletes who are
      interested in developing 1RM strength in the bench press may benefit from the use
      of additional eccentric loading.

PMID- 11834101
TI  - Effects of resistance training on the sit-and-reach test in elderly women.
AB  - The study showed the effects of a 10-week resistance training program on
      flexibility of elderly women (n = 11) between 62 and 78 years of age. The control
      group was composed of 8 women (62 to 73 years old) who were physically inactive.
      Flexibility was evaluated through the sit-and-reach test, performed both before
      and after the training program. After an initial evaluation, individuals started
      a training program, which consisted of 8 exercises for the entire body, without
      the performance of any flexibility exercise. The training program resulted in
      significant increase (p < 0.001) of flexibility in elderly women (approximately
      equal 13%). No significant differences were found in the control group. We
      conclude that weight training without performance stretching exercises does
      increase flexibility in elderly women.

PMID- 11834102
TI  - Importance of health science education for personal fitness trainers.
AB  - Using a questionnaire developed for the current study, the Fitness Instructors
      Knowledge Assessment (FIKA(Copyright )), we examined relations between commonly
      used indicators of knowledge (training and experience) and actual knowledge in
      the five areas of (a) nutrition, (b) health screening, (c) testing protocols, (d)
      exercise prescription, and (e) general training knowledge regarding special
      populations. FIKA provided reliable measures of knowledge in these areas, which
      are of critical importance in developing an optimal fitness program for the
      client and for avoiding unnecessary injuries. A survey of 115 health fitness
      professionals revealed that a bachelor's degree in the field of exercise science
      and possession of American College of Sports Medicine or the National Strength
      and Conditioning Association certifications as opposed to other certifications
      were strong predictors of a personal trainer's knowledge, whereas years of
      experience was not related to knowledge. These findings suggest that personal
      fitness trainers should have licensing requirements, such as a bachelor's degree
      in exercise science and certification by an organization whose criteria are
      extensive and widely accepted, before being allowed to practice their craft.

PMID- 11834103
TI  - The effects of accentuated eccentric loading on strength, muscle hypertrophy, and
      neural adaptations in trained individuals.
AB  - The purpose of this study was to compare the strength and neuromuscular
      adaptations for dynamic constant external resistance (DCER) training and dynamic
      accentuated external resistance (DAER) training (resistance training employing an
      accentuated load during eccentric actions). Male subjects active in resistance
      training were assigned to either a DCER training group (n = 10) or a DAER
      training group (n = 8) for 9 weeks. Subjects in the DCER group performed 4 sets
      of 10 repetitions with a load of 75% concentric 1 repetition maximum (RM).
      Subjects in the DAER group performed 3 sets of 10 repetitions with a concentric
      load of 75% of 1RM and an eccentric load of approximately 120% of concentric 1RM.
      Three measures reflecting adaptation of elbow flexors and extensors were recorded
      pretraining and posttraining: concentric 1RM, muscle cross-sectional area (CSA),
      and specific tension. Strength was assessed at midtraining periods. No
      significant changes in muscle CSA were observed in either group. Both training
      groups experienced significant increases in concentric 1RM and specific tension
      of both the elbow flexors and extensors, but compared with DCER training, DAER
      training produced significantly greater increases in concentric 1RM of the elbow
      extensors. These results suggest that, for some exercises, DAER training may be
      more effective than DCER training in developing strength within a 9-week training
      phase. However, for trained subjects, neither protocol is effective in eliciting
      muscle hypertrophy.

PMID- 11834104
TI  - The effect of flexible magnets on hand muscle strength: a randomized, double
      blind study.
AB  - The purpose of this study was to determine the effect of a flexible magnet on
      hand grip and thumb-forefinger pinch strength. Flexible magnet use has become
      popular in sports medicine and rehabilitation for a number of reasons, including
      augmenting muscle force output. Thirty-five university students (18 men and 17
      women) volunteered for this study. Each subject was tested for grip strength
      (grip dynamometer) and thumb-forefinger pinch strength (pinch gauge) under 3
      different treatment conditions: baseline (no magnet), sham magnet (placebo), and
      flexible magnet (700-G intensity). The order of treatments was randomly assigned,
      and all data collection followed a double-blind format. For grip strength
      measurements, magnet placement was over the bellies of the flexor digitorum
      profundus and flexor digitorum superficialis, and for pinch strength
      measurements, it was over the bellies of the flexor pollicis brevis and opponens
      pollicis. Three trials for each strength measurement for each of the 3 conditions
      were performed. Magnets (700 G or sham) were placed on the appropriate areas of
      the skin 3 minutes before the first test trial, with each subsequent test trial
      separated by 1 minute. Comparison among the 3 treatment conditions was analyzed
      using a 1-way analysis of variance (ANOVA) with repeated measures. ANOVA revealed
      no statistically significant (p > 0.05) mean differences for strength among any
      of the 3 treatments (baseline, 700-G magnet, or sham magnet) for either hand grip
      or thumb-forefinger pinch within each sex subgroup or for the combined group. The
      findings indicate that flexible magnets with a field strength of 700 G do not
      increase muscle strength.

PMID- 11834105
TI  - Hypohydration adversely affects lactate threshold in endurance athletes.
AB  - The purpose of this investigation was to observe the effect of hypohydration (-4%
      body mass) on lactate threshold (LAT) in 14 collegiate athletes (8 men and 6
      women; age, 20.9 +/- 0.5 years; height, 171.1 +/- 2.4 cm; weight, 64.8 +/- 2.3
      kg; V(O)2 max, 62.8 +/- 1.9 ml x kg(-1) x min(-1); percentage of fat, 11.4 +/-
      1.5%). Subjects performed 2 randomized, discontinuous treadmill bouts at a dry
      bulb temperature (T(db)) of 22 degrees C to volitional exhaustion in 2 states of
      hydration, euhydrated and hypohydrated. The hypohydrated condition was achieved
      in a thermally neutral environment (T(db), 22 degrees C; humidity, 45%), with
      exercise conducted at a moderate intensity as defined by rating of perceived
      exertion (RPE, approximately 12) 12-16 hours before testing. On average, subjects
      decreased 3.9% of their body mass before the hypohydration test. Blood lactate,
      hematocrit, V(O)2, minute ventilation (VE), R value, heart rate (HR), and RPE
      were measured during each 4-minute stage of testing. In the hypohydrated
      condition, LAT occurred significantly earlier during exercise and at a lower
      absolute V(O)2, VE, respiratory exchange ratio, RPE, and blood lactate
      concentration. Also, the blood lactate concentration was significantly lower in
      the hypohydrated condition (6.7 +/- 0.8 mmol) compared with the euhydrated
      condition (10.2 +/- 0.9 mmol) at peak exercise. There were no differences in HR
      or percentage of maximum HR at LAT nor did plots of V(CO2):V(O)2 reveal
      differences in bicarbonate buffering during exercise between the 2 conditions.
      From these results, we speculate that hypohydration did not significantly alter
      cardiovascular function or buffering capacity but did cause LAT to occur at a
      lower absolute exercise intensity.

PMID- 11834106
TI  - The effects of training history, player position, and body composition on
      exercise performance in collegiate football players.
AB  - Performance data for 261 NCAA Division 1A collegiate football players were
      analyzed to determine if player position, body weight, body fat, and training
      time were correlated with changes in performance in the following events: power
      clean (PC), bench press (BP), squat (SQ), vertical jump (VJ), 40-yd dash (40yd),
      and 20-yd shuttle (20yd). Individual positions were combined into the following
      groups: (A) wide receivers, defensive backs, and running backs, (B) linebackers,
      kickers, tight ends, quarterbacks, and specialists, and (C) linemen. Increases in
      body weight were positively correlated with increases in BP and PC performance
      for all groups. Increases in body fat were negatively correlated with performance
      in the PC and VJ for all groups. For group C, increases in body fat were also
      negatively correlated with performance in the 40yd and 20yd. Group and training
      time exhibited no linear relationship with performance in any of the tested
      events. No linear relationships were observed between the independent variables
      and performance in the SQ. When individual training data were analyzed
      longitudinally, a nonlinear increase in performance in the PC, BP, and SQ was
      observed as training time increased, with the greatest rate of change occurring
      between the first and second semesters of training.

PMID- 11834108
TI  - Standardization and validation of the body weight adjustment regression equations
      in Olympic weightlifting.
AB  - The problems in comparing the performances of Olympic weightlifters arise from
      the fact that the relationship between body weight and weightlifting results is
      not linear. In the present study, this relationship was examined by using a
      nonparametric curve fitting technique of robust locally weighted regression
      (LOWESS) on relatively large data sets of the weightlifting results made in top
      international competitions. Power function formulas were derived from the fitted
      LOWESS values to represent the relationship between the 2 variables in a way that
      directly compares the snatch, clean-and-jerk, and total weightlifting results of
      a given athlete with those of the world-class weightlifters (golden standards). A
      residual analysis of several other parametric models derived from the initial
      results showed that they all experience inconsistencies, yielding either
      underestimation or overestimation of certain body weights. In addition, the
      existing handicapping formulas commonly used in normalizing the performances of
      Olympic weightlifters did not yield satisfactory results when applied to the
      present data. It was concluded that the devised formulas may provide objective
      means for the evaluation of the performances of male weightlifters, regardless of
      their body weights, ages, or performance levels.

PMID- 11834107
TI  - The acute 1-week effects of the Zone diet on body composition, blood lipid
      levels, and performance in recreational endurance athletes.
AB  - The aim of this study was to examine the effects of a 7-day Zone diet compared
      with a normal diet on maximal oxygen uptake (V(O)2 max), running time to
      exhaustion during endurance performance, and body composition. Eight men, with
      the following physical characteristics (mean +/- SE), participated in this study:
      age, 26.1 +/- 1.9 years; height, 178 +/- 1.7 cm; mass, 70.7 +/- 2.1 kg; and V(O)2
      max, 54.6 +/- 3.1 ml x kg(-1) x min(-1). All subjects undertook pretesting for
      V(O)2 max, time to exhaustion (80% V(O)2 max), and body composition (Biostat
      1500) before following either the normal diet or the Zone diet for 7 days. These
      performance trials were performed before and after the dietary period. There was
      a significant (p < 0.05) decrease in total energy consumption from a mean of
      2,314 +/- 334 kcal on a pretest diet to 1,994 +/- 438 kcal on the Zone diet.
      Subjects showed a significant reduction (p < 0.02) in body mass from 70.7 +/- 2.1
      kg to 69.8 +/- 2.1 kg. In the 80% V(O)2 max time to exhaustion trial, there was a
      significant reduction (p < 0.05) in time to exhaustion from 37.68 +/- 8.6 minutes
      for the pretest diet to 34.11 +/- 7.01 minutes for the Zone diet. In conclusion,
      the claim of the authors of the Zone diet that performance time and V(O)2 max can
      be improved was not shown in this 1-week research trial. We would suggest that
      this is not a nutritional strategy that athletes should use until further work
      has been conducted.

PMID- 11834110
TI  - Explosive strength deficit as a predictor of vertical jumping performance.
AB  - Currently, variables predictive of vertical jumping performance can account for
      only part of its total variability. A potential additional source of variation
      called explosive strength deficit (ESD) was described in 1995 by Zatsiorsky
      (Science and Practice of Strength Training. Champaign, IL: Human Kinetics, 1995.
      pp. 34-35.). ESD is determined by measuring the maximum force generated under
      ideal circumstances (F(mm)) and under task-relevant conditions (F(m)). It is
      calculated as 100(F(mm) - F(m))/F(m). For this study, the following operational
      definitions were used: F(mm) = squatting peak force at 0.51 m x s(-1); F(m) =
      squatting peak force at 1.43 m x s(-1). Data were analyzed using forward stepwise
      multiple regression. Mean ESD for men was 29.7% (SD = 11.7) and for women was
      49.3% (SD = 11.2). For men and women, respectively, zero-order correlations for
      ESD with restricted vertical jumping (RVJ) distance were -0.35 and -0.60, and
      between ESD and drop vertical jumping (DVJ) distance were -0.20 and -0.63.
      However, when the previously identified predictors were taken into account, ESD
      was not a significant predictor (p > 0.05) of either type of jump. Therefore, it
      was concluded that ESD on the basis of velocity-regulated squats does not augment
      the explained variance previously established for vertical jumping performance.

PMID- 11834109
TI  - The effect of heavy- vs. light-load jump squats on the development of strength,
      power, and speed.
AB  - The purpose of this investigation was to examine the effect of an 8-week training
      program with heavy- vs. light-load jump squats on various physical performance
      measures and electromyography (EMG). Twenty-six athletic men with varying levels
      of resistance training experience performed sessions of jump squats with either
      30% (JS30, n = 9) or 80% (JS80, n = 10) of their one repetition maximum in the
      squat (1RM) or served as a control (C, n = 7). An agility test, 20-m sprint, and
      jump squats with 30% (30J), 55% (55J), and 80% (80J) of their 1RM were performed
      before and after training. Peak force, peak velocity (PV), peak power (PP), jump
      height, and average EMG (concentric phase) were calculated for the jumps. There
      were significant increases in PP and PV in the 30J, 55J, and 80J for the JS30
      group (p <or= 0.05). The JS30 group also significantly increased in the 1RM with
      a trend towards improved 20-m sprint times. In contrast, the JS80 group
      significantly increased both PF and PP in the 55J and 80J and significantly
      increased in the 1RM but ran significantly slower in the 20-m sprint. In the 30J
      the JS30 group's percentage increase in EMG activity was significantly different
      from the C group. In the 80J the JS80 group's percentage increase in EMG activity
      was significantly different from the C group. This investigation indicates that
      training with light-load jump squats results in increased movement velocity
      capabilities and that velocity-specific changes in muscle activity may play a key
      role in this adaptation.

PMID- 11834111
TI  - Ratings of perceived exertion in active muscle during high-intensity and low
      intensity resistance exercise.
AB  - This investigation compared ratings of perceived exertion specific to the active
      muscles used during resistance exercise (RPE-AM) using the 15-category Borg scale
      during high-intensity (HIP) and low-intensity (LIP) weight lifting. Ten men (23.2
      +/- 3.6 years) and 10 women (21.8 +/- 2.7 years) performed 2 trials consisting of
      seven exercises: bench press (BP), leg press, latissimus dorsi pull down, triceps
      press, biceps curl, shoulder press, and calf raise. The HIP and LIP protocols
      were completed in counterbalanced order. During HIP, subjects completed 5
      repetitions using 90% of 1 repetition maximum (1RM). RPE-AM was measured after
      every repetition. During LIP, subjects completed 15 repetitions using 30% of 1RM.
      RPE-AM was measured after every third repetition. RPE-AMs were greater (p <or=
      0.001) for HIP than for LIP for each exercise. For example, the mean initial BP
      RPE was 14.11 +/- 2.08 for the HIP and 8.34 +/- 1.35 for the LIP. Performing few
      repetitions using heavier weight is perceived to be more difficult than lifting
      comparatively lighter weight with more repetitions when external work is held
      constant.

PMID- 11834112
TI  - Effects of a 4-month season on glenohumeral joint rotational strength and range
      of motion in female collegiate tennis players.
AB  - The purpose of this study was to examine the effects of a 4-month season of
      collegiate tennis on glenohumeral joint internal and external rotation strength
      and range of motion in female collegiate tennis players. Eleven female collegiate
      tennis players were isokinetically tested to assess glenohumeral joint internal
      and external rotation strength with 90 degrees of abduction on a Cybex 6000
      isokinetic dynamometer. Subjects were also measured for internal and external
      rotation range of motion using a universal goniometer with 90 degrees of
      abduction. Measurements were taken before and immediately after a 4-month season
      of competitive collegiate tennis play. A repeated-measures analysis of variance
      showed no significant difference in internal or external rotation strength or
      range of motion between pre- and postseason measures. Results from this study
      show that, despite 4 months of competitive tennis play, changes in rotational
      strength and range of motion did not occur. These data have implications for
      clinicians as well as strength and conditioning professionals designing
      rehabilitation and preventative conditioning programs for athletes in this
      population.

PMID- 11834113
TI  - Blood lactate and stroke parameters during front crawl in elite swimmers with
      disability.
AB  - The purpose of this investigation was to compare the blood lactate concentration
      ([La]), stroke distance (D(s)), and swim index (SI) during an incremental swim
      test (IST) in elite swimmers who had a loss in mobility (LM) (n = 6) or who had
      full mobility (FM) (n = 5) of the lower limbs. The IST consisted of 5 repeats of
      either 100 or 200 m front crawl depending upon the ability level of the swimmer.
      The [La] and heart rate measured during the IST showed no significant differences
      (p > 0.05). However, velocity (V(s)) and D(s) were all significantly lower (p <
      0.01) during the IST. SI was significantly (p < 0.01) lower during repeats 1 to 3
      and 5, but not repeat 4. These data indicate that the [La] response to
      incremental exercise is similar during incremental front crawl activity in
      swimmers suffering from loss of lower limb mobility. However, a critical V(s) is
      reached in LM swimmers where swimming efficiency is optimal compared with FM
      swimmers.

PMID- 11834114
TI  - Use of diagnostic ultrasound for assessing muscle size.
AB  - The typical "gold standard" for assessing muscle size has been magnetic resonance
      imaging (MRI) and computerized tomography; however, these processes are very
      expensive and generally require a medical facility. The advent of B-mode
      diagnostic ultrasound (US) can perhaps offer a quick, cost-effective method to
      measure muscle size. The purpose of this study was to document the reliability of
      B-mode US for assessing muscle size in a variety of populations. Thirty-eight
      postmenopausal women (avg. age = 58.9 +/- 0.7 years) had both their right rectus
      femoris and biceps brachii imaged, 85 older men and women (avg. age = 65.0 +/-
      0.4 yrs) had their right rectus femoris imaged, and 10 young men and women (avg.
      age = 26.1 +/- 2.4 yrs) had their right rectus femoris imaged by both US and MRI.
      The location used for imaging on the right rectus femoris was a point 15 cm above
      to the superior border of the patella following the midline of the anterior
      surface of the thigh, whereas the biceps brachii was measured at maximal girth
      following the midline of the anterior surface of the upper arm. All trials
      utilizing US (Fukuda Denshi, model 4500) and a 5 Mz transducer (FUT-L104) were
      obtained in duplicate on 2 separate days. The young subjects that also had their
      rectus femoris measured by MRI were imaged with a Picker 1.5 Tesla (The Edge),
      which used a fast spin sequence and 192 x 256 resolution to obtain 2 5-mm-thick
      slices separated by a 1-mm-thick space. All intraclass correlation coefficients
      for the various groups and muscles measured by US ranged from r = 0.72-0.99,
      whereas coefficients of variation (CVs) ranged between 3.5% and 6.7%. The
      intraclass correlation for the MRI images was r = 0.90 and the CV was 5.2%. In
      conclusion, it appears that diagnostic US can provide a reliable and cost
      effective alternative method for assessing muscle.

PMID- 11834115
TI  - Effect of recovery interval on multiple-bout sprint cycling performance after
      acute creatine supplementation.
AB  - The purpose of this study was to examine the effect of varying recovery intervals
      on multiple-bout, short-duration, high-intensity cycling efforts of adult men
      supplemented with creatine (Cr) or a placebo (Pl). Thirty subjects underwent 3
      trials of a maximal cycling protocol (T(0), T(1), T(2)). T(0) included V(O)2 max
      testing and familiarization with the sprint cycling protocol. T(1) consisted of 8
      15-second bouts of sprint cycling exercise. Subjects were randomly assigned to
      recovery interval groups (1 minute, 3 minutes, 6 minutes), and Cr or Pl groups
      (0.3 g x kg(-1) x d(-1)). Posttesting (T(2)) took place 7 days after T(1) and
      consisted of an identical protocol as during T(1). Changes in mean power (MP),
      peak power (PP), and fatigue index (FI) were compared between trials. MP was
      significantly increased in Cr 1-minute, Cr 3-minute, and Pl 6-minute groups (p <
      0.05). Significant PP increases were demonstrated in Cr 1-minute and Pl 6-minute
      groups (p < 0.05), and FI significantly increased in Pl 1-minute group (p <
      0.05). Results indicate that Cr supplementation is effective in improving
      recovery from repeated sprint cycling performances when the recovery interval is
      of a short (<6 minutes) duration.

PMID- 11834116
TI  - Repeated eccentric exercise bouts do not exacerbate muscle damage and repair.
AB  - This study examined whether performing repeated bouts of eccentric exercise 2 and
      4 days after an initial damaging bout would exacerbate muscle damage. One arm
      performed 3 sets of 10 eccentric actions of the elbow flexors (ECC1) using a
      dumbbell set at 50% of the maximal isometric force at 90 degrees (SINGLE). Two
      weeks later the same exercise was performed by the opposite arm with the
      exception that subsequent bouts were performed 2 (ECC2) and 4 (ECC3) days after
      ECC1 (REPEATED). In the REPEATED condition, maximal isometric force (MIF)
      decreased to the same level immediately after ECC1-3, and the decreases in range
      of motion (ROM) and increases in upper arm circumference immediately postexercise
      were similar among the bouts. However, no significant differences in changes in
      MIF, ROM, muscle soreness, and plasma creatine kinase activity were evident
      between the SINGLE and REPEATED conditions when excluding the changes immediately
      after ECC2 and ECC3. These results suggest that ECC2 and ECC3 did not exacerbate
      muscle damage or affect the recovery process.

PMID- 11834117
TI  - Effects of low-intensity resistance exercise with short interset rest period on
      muscular function in middle-aged women.
AB  - We investigated the effect of low-intensity resistance exercise training on
      muscular size and strength where the interset rest period was shortened so as to
      reduce the metabolite clearance. Female subjects (aged 45.4 +/- 9.5 years, n =
      10) performed bilateral knee extension exercises in a seated position on an
      isotonic leg extension machine. The exercise sessions consisted of 3 sets of
      exercise at a mean intensity of approximately 50% 1RM with an interset rest
      period of 30 seconds and was performed twice a week for a period of 12 weeks. The
      strength and the cross-sectional area (CSA) of the knee extensors and flexors
      were examined with an isokinetic dynamometer and magnetic resonance imaging
      (MRI), respectively. The CSAs of the knee extensors and flexors increased by 7.1
      +/- 1.6% (p < 0.01, Wilcoxon signed rank test) and 2.5 +/- 1.4% (not
      significant), respectively. Isometric and isokinetic strengths increased
      significantly (p < 0.01) at all velocities examined, whereas no significant
      change was observed in those of knee flexors. These results indicate that a low
      intensity resistance exercise with a short interset rest period is substantially
      effective in inducing muscular hypertrophy and concomitant increase in strength.

PMID- 11834118
TI  - Electromyographic comparison of standard and modified closed-chain isometric knee
      extension exercises.
AB  - The purpose of this study was to compare electromyographic (EMG) activity during
      open kinetic chain (OKC) and a modified closed kinetic chain (MCKC) knee
      extension exercises. Both OKC and closed kinetic chain (CKC) exercises provide
      benefits when devising conditioning programs; however, there are no exercises
      that combine the benefits of both exercises. Subjects performed maximum isometric
      knee extensions for both traditional OKC and MCKC knee extension exercises.
      Surface electrodes were placed on 8 lower-extremity muscles. One second of
      integrated EMG activity followed 95% maximal knee extension force. The following
      muscles demonstrated greater EMG activity during the MCKC vs. the OKC knee
      extension exercises: vastus medialis, medial hamstring, lateral hamstrings, and
      gluteus maximus. There was no difference between force output between the 2
      conditions. This study demonstrates that modifications to traditional OKC
      exercises demonstrate some characteristics of CKC exercises, and therefore
      provide another avenue of rehabilitation or strengthening.

PMID- 11834119
TI  - A kinematic comparison of four abdominal training devices and a traditional
      abdominal crunch.
AB  - Abdominal exercises are often performed on roller or rocker mechanisms, which
      have been aggressively promoted through the television and print media. However,
      justifications are lacking as to why these devices are superior to traditional
      abdominal exercises such as crunches. This study sought to describe and compare
      the range of motion (ROM) of several joints during crunches performed on 4
      different abdominal conditioning devices (2 roller and 2 pivot types) and a
      traditional crunch exercise. Ten men (29 +/- 5.87 years, 177.5 +/- 6.46 cm, 80.96
      +/- 11.72 kg) and 10 women (33.4 +/- 10.16 years, 162.23 +/- 3.83 cm, 56.99 +/-
      7.36 kg) subjects agreed to participate in the study. Subjects were videotaped in
      the sagittal plane (60 Hz) using standard kinematic methods. Reflective markers
      were placed on the right temple, auditory meatus, shoulder, hip, knee, ankle,
      heel, toe, and 2 sternum markers placed on a foam piece strapped to the subject's
      chest. The videotaped movements were automatically digitized (PEAK5 2-D) and the
      data smoothed using a Butterworth filter. Relative angular ROMs of the head
      (temple, auditory meatus, shoulder); neck (auditory meatus, shoulder, hip); trunk
      (near sternum, shoulder, hip); hip (shoulder, hip, knee); sternum/head (sternum
      near and sternum far with temple and auditory meatus); sternum/trunk (sternum
      near and sternum far with shoulder and hip); and a sum of 4 angles (head, neck,
      trunk, hip) were calculated. Sex by equipment repeated measures analyses of
      variance (ANOVAs) were calculated on the angles of the 5 exercises. When no main
      effect for sex was found, the data were collapsed across sex and a one-way ANOVA
      with repeated measures was calculated on the resulting data. Post hoc analyses of
      pairwise differences were calculated using Tukey's honestly significant
      difference statistic. Results showed that crunches performed with the abdominal
      devices resulted in less ROM in all angles measured when compared with a
      traditional crunch. The traditional crunch exercise was most closely simulated by
      the pivot-type devices. The results indicated that prescription of abdominal
      conditioning exercises via these devices results in training through smaller ROMs
      compared with a traditional crunch. The specific angle changes may require
      careful judgment as to appropriate application for exercisers with specific back
      and neck motion limitations.

PMID- 11834120
TI  - Evaluation of a new anaerobic power testing system.
AB  - The purpose of this study was to evaluate the reliability of a new anaerobic
      athletic performance system. This system is proposed to assess vertical jump
      height, anaerobic power through repetitive jumping, and reaction to both an
      auditory and visual stimulus. One hundred twenty-three subjects (92 men and 31
      women; mean +/- SD: age, 20.5 +/- 2.1 years; body weight, 83.1 +/- 20.4 kg;
      height, 176.0 +/- 9.2 cm) volunteered to participate. To assess reliability of
      the new testing device, subjects were tested on 3 separate occasions (T1, T2, and
      T3). At least 72 hours but not more than 1 week separated each laboratory visit.
      During each testing session subjects performed a countermovement jump (CMJ), a 30
      consecutive jumps anaerobic power test (30JT), and reaction to both an auditory
      and visual stimulus. Results showed no differences between T1, T2, and T3 in
      either CMJ height or 30JT assessments. However, reaction to an audible or visual
      stimulus significantly improved during each testing session. Intraclass
      reliability of the CMJ and the 30JT was greater than 0.96 across the 3 trials.
      Pearson correlation coefficients of r > 0.90 were seen for the CMJ and 30JT,
      indicating a high test-retest reliability. The test-retest reliability for the
      reaction tests were lower (r ranging from 0.72 to 0.83). A Bland-Altman plot
      showed limited agreement between methods of vertical jump height assessment.
      Results indicate that this new testing device shows high reliability to assess
      both CMJ height and anaerobic power. In addition, anaerobic power assessment in a
      jump test provides a specific measure of anaerobic power for many sports
      incorporating similar performance patterns.

PMID- 11834121
TI  - Reliability of an exercise protocol designed to evaluate resistance exercise
      performance.
AB  - The purpose of the present investigation was to evaluate the reliability a
      protocol used to assess short-term resistance exercise performance. Six men
      participated in this investigation after giving their consent. Subjects (N = 6)
      performed 6 sets of leg extensions at 80% of 10 repetition maximum (RM). Ten
      repetitions were performed during the first 3 sets; during the last 3 sets
      subjects exercised to fatigue. Ninety seconds of seated passive recovery
      separated each set. Subsequently, 2 experimental trials were conducted in which
      the exercise protocol was identical to the familiarization trial. There was a
      significant decline in performance from set 4 (13.5 +/- 0.9 reps) to set 5 (11.9
      +/- 0.8 reps) and set 4 to set 6 (10.8 +/- 1.0 reps), suggesting that the
      protocol did induce fatigue. The intraclass correlations were 0.992, 0.992, and
      0.993 for the fourth, fifth, and sixth sets, respectively. The average
      coefficients of variation for the fourth, fifth, and sixth sets were 6.7, 2.7,
      and 7.1%, respectively. These data suggest that the resistance training protocol
      used in this investigation is reliable and may be useful in evaluating
      interventions designed to improve fatigue resistance.

PMID- 11834122
TI  - Effects of a sports nutrition bar on endurance running performance.
AB  - The Access bar claims to contain adenosine antagonists and a precise mixture of
      macronutrients that are purported to improve aerobic performance by increasing
      fat metabolism and providing sustained exogenous energy. The purpose of this
      research was to examine the effect of the Access bar on endurance running
      performance. Twelve active, healthy runners completed 5 sessions: a V(O)2 max
      test, a 30-minute familiarization session, and 3 experimental sessions. During
      each experimental session subjects ran a self-paced, simulated race on a
      treadmill (approximately 55 minutes) until they had completed a set energy
      expenditure target (0.8368 kJ x 60 minutes x body mass). Fifteen minutes before
      exercise subjects received either the Access bar and water, Uncle Tobys Peanut
      Butter Muesli Bar and water, or Crystal Light, using a randomized, double-blind
      design. Heart rate, oxygen consumption, respiratory exchange ratio, and running
      speed were measured every minute during testing. Blood lactate and rating of
      perceived exertion were assessed at selected intervals; time to finish was also
      recorded. Analysis of variance showed no significant difference between the 3
      treatments in any of the measures. These results do not support the use of the
      Access Sports Nutrition Bar to enhance endurance running performance of
      approximately one hour.

PMID- 11834123
TI  - The effects of high-dose glutamine ingestion on weightlifting performance.
AB  - The purpose of this study was to determine if high-dose glutamine ingestion
      affected weightlifting performance. In a double-blind, placebo-controlled,
      crossover study, 6 resistance-trained men (mean +/- SE: age, 21.5 +/- 0.3 years;
      weight, 76.5 +/- 2.8 kg(-1)) performed weightlifting exercises after the
      ingestion of glutamine or glycine (0.3 g x kg(-1)) mixed with calorie-free fruit
      juice or placebo (calorie-free fruit juice only). Each subject underwent each of
      the 3 treatments in a randomized order. One hour after ingestion, subjects
      performed 4 total sets of exercise to momentary muscular failure (2 sets of leg
      presses at 200% of body weight, 2 sets of bench presses at 100% of body weight).
      There were no differences in the average number of maximal repetitions performed
      in the leg press or bench press exercises among the 3 groups. These data indicate
      that the short-term ingestion of glutamine does not enhance weightlifting
      performance in resistance-trained men.

PMID- 11834124
TI  - A peroxidase isoenzyme secreted by turnip (Brassica napus) hairy-root cultures:
      inactivation by hydrogen peroxide and application in diagnostic kits.
AB  - We have purified various peroxidase isoenzymes from roots and hairy-root cultures
      of turnip (Brassica napus) which could potentially be used for commercial
      applications such as an enzyme immunoassays, diagnostic test kits, wastewater
      treatment and soil remediation. One of them, a basic peroxidase called HR2, was
      secreted into the medium of turnip hairy-root cultures. HR2 had a pI of 9.6, a
      molecular mass of 39.3 kDa and showed great thermostability. The inactivation of
      HR2 by H2O2 in the absence of reductant substrates was studied. Under these
      conditions H2O2 acted as a suicide substrate. The kinetic constants calculated
      have been compared with those of a basic isoperoxidase from horseradish
      (Armoracia sp.) roots (HRP-C), which is commonly used in commercial kits. The
      results for HR2 indicated that it was more resistant to inactivation because it
      presented a lower inactivation efficiency and a higher value for the partition
      ratio (r=1250) than those described for HRP-C. These results make turnip
      peroxidase HR2 suitable for use in systems in which high H2O2 concentrations are
      found. Such an application is demonstrated, namely an enzymic diagnostic kit for
      determination of uric acid in which HR2 was found to be as efficient as the
      enzyme originally included in standard kits.

PMID- 11834125
TI  - Resolving the DDT target protein in insects as a subunit of the ATP synthase.
AB  - 1,1-bis-(p-Chlorophenyl)-2,2,2-trichloroethane (DDT) inhibited the ATP hydrolytic
      activity of the ATP synthase from a DDT-susceptible insect (Apis mellifera) as
      well as a DDT-tolerant insect (Spodoptera littoralis), and from rat liver and
      bovine heart in a parallel way to its insecticidal properties and selectivity of
      action. Inhibition of the ATPase activity of these preparations by DDT was
      parallel to the poisoning of the source organism with DDT. Furthermore, both the
      inhibition and poisoning of insects were affected similarly by temperature.
      Inhibition of the insect enzyme activity by DDT was specific and differed from
      that by oligomycin or N,N-dicyclohexylcarbodi-imide (DCCD). PAGE analysis of the
      various preparations of the enzyme showed that the inhibition of the enzyme
      activity by DDT was associated with the presence of a selective protein band with
      an apparent molecular mass of 23 kDa. This protein band exists in the
      preparations from the DDT-susceptible insects but was absent from the
      preparations of the enzyme from the DDT-insensitive sources. Removal of this
      protein band from the enzyme rendered its activity insensitive to inhibition by
      DDT. The protein was purified directly from mitochondria and the DDT sensitivity
      was reconstituted upon its addition to the DDT-insensitive F1-ATPase. We conclude
      that this identified protein of the ATP synthase is the DDT target protein in
      insects.

PMID- 11834126
TI  - High-level expression of human thyroid-stimulating hormone in Chinese hamster
      ovary cells by co-transfection of dicistronic expression vectors followed by a
      dual-marker amplification strategy.
AB  - The utilization of dicistronic mRNA expression vectors, containing the gene of
      interest upstream of an amplifiable marker gene, has shown success in rapidly,
      efficiently and reproducibly obtaining stable cell lines that express high levels
      of the protein of interest. For this reason, human thyroid-stimulating hormone
      (hTSH), a heterodimeric glycoprotein composed of non-covalently linked alpha- and
      beta-subunits, was expressed in Chinese hamster ovary (CHO) cells using a system
      based on dicistronic expression vectors. These contained the genes of interest
      and the amplifiable gene markers dihydrofolate reductase (DHFR) and adenosine
      deaminase (ADA), separated by an internal ribosome entry site isolated from the
      encephalomyocarditis virus. After the cells (CHO-DHFR-) had been co-transfected
      with the expression vectors and submitted to gene amplification in culture medium
      containing stepwise increments of methotrexate, it was possible to isolate clones
      that presented a secretion level of up to 7.2+/-1.3 microg/10(6) cells per day,
      the highest ever reported for the expression of this glycoprotein hormone. A
      second treatment, involving the utilization of deoxycoformycin, directed to
      amplify the ADA marker gene, provided a clone with an additional 2-3-fold
      increase in hTSH secretion, reaching a secretion level of 17.8+/-7.6 microg/10(6)
      cells per day. Cell culture and hTSH production in a hollow-fibre bioreactor were
      set up in order to carry out a preliminary physico-chemical, immunological and
      biological characterization of this hormone in comparison with pituitary
      extracted hTSH (from the National Institute of Diabetes and Digestive and Kidney
      Diseases) and the only recombinant hTSH now available (Thyrogen). The
      availability of recombinant hTSH is very important in the diagnosis and therapy
      of thyroid carcinoma, via stimulation of radioiodine uptake.

PMID- 11834127
TI  - Catalytic activities of intracellular dimeric neopullulanase on cyclodextrin,
      acarbose and maltose.
AB  - Multi-substrate specificity of neopullulanase towards cyclodextrin, acarbose and
      maltose was investigated using a clone originating from Bacillus
      stearothermophilus IMA6503. The enzyme purified from Escherichia coli harbouring
      the corresponding nplA gene hydrolysed beta-cyclodextrin (beta-CD) to maltose and
      glucose. It exhibited substrate preference for beta-CD, starch and pullulan in
      the proportions of 10.4:1.2:1. The enzyme not only hydrolysed acarbose, an alpha
      amylase inhibitor, to a pseudotrisaccharide (PTS) and glucose, but also
      transferred PTS to glucose, forming isoacarbose. Moreover, it hydrolysed maltose
      to glucose and transferred the glucose to another maltose molecule to form panose
      when maltose was present at a low concentration (0.5%) in the reaction solution.
      The enzyme catalysed condensation between two maltose molecules and subsequent
      hydrolysis of the resulting 6(2)-O-alpha-maltosyl-maltose to glucose and panose,
      when maltose concentration was increased to 20%. Neopullulanase was likely to be
      present in monomer-dimer equilibrium with a molar ratio of 1:9 in 50 mM sodium
      acetate buffer (pH 6.0). The association-dissociation equilibrium of
      neopullulanase was shifted to monomerization by KCl. When the content of monomer
      increased in the reaction mixture, the specific activity towards soluble starch
      increased to 150%, while that towards beta-CD decreased to 80%. Therefore, multi
      substrate specificity of neopullulanase was likely to be modulated by the shift
      of monomer-dimer association equilibrium.

PMID- 11834128
TI  - Oligo-1,6-glucosidase from a thermophile, Bacillus thermoglucosidasius KP1006,
      was efficiently produced by combinatorial expression of GroEL in Escherichia
      coli.
AB  - To improve the production of oligo-1,6-glucosidase from the obligately
      thermophilic Bacillus thermoglucosidasius KP1006 in Escherichia coli, the
      combined expression of oligo-1,6-glucosidase with various chaperone proteins of
      Hsp (heat-shock protein) 60 team proteins (GroES and GroEL) or Hsp70 team
      proteins (GrpE, DnaK and DnaJ) from the same thermophile was examined. This
      attempt was based on the facts that, (i) among glycosyl hydrolases of Family 13,
      bacillary oligo-1,6-glucosidases share highest homology with yeast alpha
      glucosidase, and (ii) this yeast enzyme interacts with GroEL. In B.
      thermoglucosidasius Hsp60 team proteins, in particular, GroEL brought about a
      remarkable rise in expression of B. thermoglucosidasius oligo-1,6-glucosidase,
      while Hsp70 team proteins had no significant effect. The effect of B.
      thermoglucosidasius GroEL on oligo-1,6-glucosidase expression was supported by
      the finding that thermally inactivated B. thermoglucosidasius oligo-1,6
      glucosidase was revived by B. thermoglucosidasius GroEL. Although the molecular
      mass of B. thermoglucosidasius oligo-1,6-glucosidase (66 kDa) exceeds the major
      range of substrates for GroEL proteins, the GroEL molecules probably recognized
      the alpha/beta motifs contained in the N-terminal domain and the subdomain of the
      oligo-1,6-glucosidase. Here we show that (i) the production of B.
      thermoglucosidasius oligo-1,6-glucosidase in E. coli was improved 3.8-fold by
      Hsp60 team proteins, (ii) the system can function for the expression of other
      glycosyl hydrolases of Family 13 that have defects in expression and (iii) the
      combinatorial expression of thermostable proteins with GroEL from the same
      thermophile in E. coli can increase the production of thermostable enzymes,
      preventing problems derived from differences in protein biogenesis.

PMID- 11834129
TI  - Cashew-tree (Anacardium occidentale L.) exudate gum: a novel bioligand tool.
AB  - The potential of bioaffinity as a tool for the study of biological-recognition
      mechanisms is gaining increasing value. The search continues for alternative
      products that can be obtained from renewable sources, such as the bark exudate
      gum from the cashew tree (Anacardium occidentale L.), which grows wild in many
      tropical and subtropical countries. Its potential use as a chromatographic matrix
      and/or for bioaffinity ligand for proteins (lectins) has been investigated. The
      crude gum was cross-linked in order to obtain a kind of chromatographic matrix
      (gel). To evaluate the gum's ability to retain glycoproteins (lectins), affinity
      chromatography was performed and, in addition, the reological behaviour of the
      gum was characterized.

PMID- 11834130
TI  - Sephadex-based cell-affinity adsorbents: preparation and performance.
AB  - Sephadex was derivatized consecutively with Staphylococcus Protein A (SpA) and
      cell-specific antibodies, and the binding of cells to the resulting material was
      examined. For comparison, cell binding to commercially obtained SpA-Sepharose was
      determined. Sephadex G-10, carboxylated by reaction with glycine and activated
      subsequently with 1-ethyl-3-(3-dimethylaminopropyl)carbodi-imide/N
      hydroxysuccinimide (NHS), was allowed to react with SpA. Coupling of SpA to NHS
      activated glycine-Sephadex appeared to be complete (immobilization capacity,
      approximately 300 microg of protein/ml of packed gel) when incubation was carried
      out at pH 4.0, in buffer of low ionic strength. However, incubation at higher pH
      values (> or = 6.5) led to poor coupling yields. After incubation with rabbit
      anti-(human red cell) antiserum, and upon mixing with human red blood cells, SpA
      glycine-Sephadex G-10 could bind up to 5 x 10(8) red cells/ml of gel. Cell
      binding increased when the amount of antiserum, added to SpA-glycine-Sephadex G
      10 for preparing the affinity gel, was increased from 0.5 to 5 microl/ml of gel.
      Compared with this, SpA-Sepharose CL 4B had to be incubated with much larger
      amounts of antiserum (100-700 microl/ml of gel) in order to obtain cell-affinity
      adsorbent. One obvious advantage of the approach described here is that
      relatively small amounts of SpA and antisera are needed for preparing cell
      affinity media.

PMID- 11834131
TI  - Enhancement of enzyme activity and enantioselectivity via cultivation in nitrile
      metabolism by Rhodococcus sp. CGMCC 0497.
AB  - Racemic 2-phenylpropionitrile was resolved enantioselectively by nitrile
      converting enzymes in cells of Rhodococcus sp. CGMCC 0497 to S-(+)-2
      phenylpropionic acid and R-(-)-2-phenylpropionamide. By optimization of the
      culture conditions, great enhancement of enzyme activity and enantioselectivity
      was achieved. Furthermore, the relationship between cell-growth periodicity and
      enzyme accumulation was studied; the addition of inducer was delayed by 1 day and
      the reaction was further improved. This unusual strategy has almost never been
      reported with other nitrile-converting strains. The resulting culture broth,
      containing methacrylamide as the inducer, beef extract as the nitrogen source and
      glucose as the carbon source, with methacrylamide added 24 h later, seemed to be
      most suitable. S-(+)-2-Phenylpropionic acid and R-(-)-2-phenylpropionamide were
      produced with yields of 48% (enantiomeric excess, 96%) and 42% (enantiomeric
      excess, 97%) respectively with no nitrile left after 3 h, or with yields of 52%
      and 39% (enantiomeric excess, 93% and 99%) respectively after 6 h.

PMID- 11834132
TI  - Quantification of right-to-left shunt with (99m)Tc-labelled albumin
      macroaggregates and 100% oxygen in patients with hereditary haemorrhagic
      telangiectasia.
AB  - Pulmonary arteriovenous malformations (PAVMs) are often associated with
      hereditary haemorrhagic telangiectasia (HHT). The quantification of right-to-left
      shunts in patients with PAVMs is important in diagnosis and follow up.
      Traditionally, this shunt is measured by the 100% oxygen method, in which the
      value for the arteriovenous difference in oxygen content, Cao(2)-CVO(2) (where
      Cao(2) is the oxygen content of arterial blood and CVO(2) is the oxygen content
      of mixed venous blood) is estimated. Alternative methods consist of measurement
      of the systemic or renal uptake of (99m)Tc-labelled macroaggregates of albumin
      (MAA), which are trapped in pulmonary capillaries, but pass through PAVMs. We
      first measured Cao(2)-CVO(2) in 12 HHT patients before and after embolization of
      PAVMs. We obtained a mean value of 4.4 ml/100 ml, instead of the usual 5 ml/100
      ml. Subsequently, we measured right-to-left shunt in 21 HHT patients using the
      100% oxygen method and with two different methods involving (99m)Tc. We used the
      kidney-lung method (K/L method), in which it is assumed that the right kidney
      receives 10% of the cardiac output, and we also used a method with two tracers
      (HSA/MAA method): (1) (99m)Tc-labelled human serum albumin (HSA) (which passes
      through pulmonary capillaries) to measure the fraction of the cardiac output
      perfusing the kidneys, and (2) MAA to measure the shunt fraction. In 35 shunt
      measurements we evaluated this new technique and the K/L method, by comparing the
      results with those from the 100% oxygen method. There was poor agreement between
      the 100% oxygen method and the K/L method, with 95% limits of agreement for the
      shunt fraction of -15.2% to +15.2%. There was moderate agreement between the 100%
      oxygen method and the HSA/MAA method, with limits of agreement of -8.3% to +7.7%.
      We conclude that the different methods cannot replace each other, because the
      limits of agreement are too wide for clinical use.

PMID- 11834133
TI  - Tibolone does not affect muscle power and functional ability in healthy
      postmenopausal women.
AB  - Maintenance of neuromuscular function into old age is critical to maintain normal
      daily activity and functional independence. Maximal muscle strength declines with
      age, and the age-related loss in power might be even greater. An accelerated loss
      of muscle strength and power has been observed in women around the time of the
      menopause. The aim of the present study was to examine the effects of tibolone, a
      synthetic steroid with oestrogenic, progestogenic and androgenic activities, on
      muscle power, endurance and functional ability. A total of 85 healthy women,
      between 1 and 15 years postmenopausal, were recruited from local paper
      advertisements. Participants were randomly assigned to 2.5 mg of tibolone or to
      placebo pills of identical appearance; pills were taken daily for 12 months,
      orally in the morning. Muscle power was assessed as explosive leg extensor power.
      Endurance was measured on a 2 min walk test and a 3.5 m walk. Functional ability
      was determined with the timed Get Up and Go test and a Postural/Locomotor/Manual
      test. No significant between-group differences were observed for any of the
      parameters. Possible explanations for this lack of effect are either the absence
      of an effect of tibolone on muscle power and functional ability, or that our
      participants were too far above their strength-related functional limits to
      derive benefit from intervention. Further research is required to resolve this
      issue.

PMID- 11834134
TI  - Changes in the pattern of bile acids in the nuclei of rat liver cells during
      hepatocarcinogenesis.
AB  - Bile acids reach the nuclei of hepatocytes, where they may play an important role
      in controlling gene expression by binding to nuclear receptors. In previous
      studies, changes in the amounts of the different molecular species of bile acids
      in the hepatocyte nucleus during rat liver regeneration have been reported. The
      aim of the present work was to investigate whether this also occurs during rat
      hepatocarcinogenesis. Liver cell nuclei were isolated after homogenization of
      livers from healthy adult rats (controls) and from rats at different time points
      during chemically induced hepatocarcinogenesis, corresponding to the stages of
      foci (12 weeks), hepatoma (20 weeks) and carcinoma (32 weeks). Bile samples from
      the cannulated common bile duct were collected for 1h from different sets of
      animals undergoing hepatocarcinogenesis. Bile acids in bile, liver homogenates
      and isolated nuclei were measured by GC-MS. Because the yield of nuclei isolated
      changed during the course of hepatocarcinogenesis (control, 20.1%; 12 weeks,
      23.6%; 20 weeks, 7.8%; 32 weeks, 5.1%), amounts of bile acids in nuclei were
      corrected for the amount of DNA in each preparation. During hepatocarcinogenesis,
      bile acid concentrations in liver homogenates were reduced to approximately half
      the values obtained in control livers, while the levels of bile acids in both
      isolated nuclei and bile were not decreased. Hepatocarcinogenesis induced changes
      in the composition of bile acid pools. These were manifest as an increase in the
      proportion of cholic acid and a decrease in that of ursodeoxycholic acid in both
      bile and liver. These modifications differed from the changes seen in the nuclear
      bile acid pool, where a decrease in the proportion of cholic acid together with
      an increase in that of ursodeoxycholic acid were the major changes observed
      during hepatocarcinogenesis. With regard to the 'flat' bile acids (allo-cholic
      acid plus Delta(5)- or Delta(4)-unsaturated bile acids), a marked
      hepatocarcinogenesis-induced increase in the output of these species in bile was
      found. However, these bile acids were only found in liver homogenates at the
      hepatoma stage, whereas they were not detected in isolated nuclei at any stage of
      hepatocarcinogenesis. In summary, these results support the existence of a bile
      acid pool in hepatocyte nuclei whose composition differs from that of the
      extranuclear bile acid pool. Moreover, they indicate that, during
      hepatocarcinogenesis, the composition of the nuclear pool undergoes important
      alterations.

PMID- 11834135
TI  - Sex steroids and insulin resistance.
AB  - There is extensive experimental evidence that sex steroids and insulin interact
      in their actions on tissues. At physiological levels, testosterone and oestradiol
      are thought to be involved in maintaining normal insulin sensitivity. However,
      outside this 'physiological window' these steroids may promote insulin
      resistance. Considerable research has been carried out on polycystic ovarian
      syndrome, a common disorder associated with excessive androgen production and
      insulin resistance. Hyperinsulinaemia in patients with this condition is believed
      to stimulate ovarian androgen production, and there is also evidence that
      androgens act directly on peripheral tissues to promote insulin resistance. There
      is the potential for a vicious circle to develop with increasing androgen
      production and insulin resistance. The molecular basis of this insulin resistance
      has been reported to involve reduced insulin receptor autophosphorylation,
      reduced expression and translocation of insulin-responsive glucose transporters
      and defects of the insulin signalling pathway distal to the insulin receptor.
      These defects await full characterization. Insulin-sensitizing agents can reverse
      many of the effects of insulin resistance and may have a future place in the
      treatment of polycystic ovarian syndrome and other conditions associated with
      steroid-induced insulin resistance. Recognition and treatment of sex steroid
      associated insulin resistance at an early stage in patients may reduce their risk
      of developing Type II (non-insulin-dependent) diabetes mellitus, hypertension and
      dyslipidaemia, and so may improve fertility and reduce cardiovascular risk. Here
      we review the interplay between sex steroids and insulin resistance, and consider
      the implications this has for clinical conditions.

PMID- 11834136
TI  - Adenosine inhibits thrombin-induced expression of tissue factor on endothelial
      cells by a nitric oxide-mediated mechanism.
AB  - Enhanced expression of tissue factor (TF) is associated with the occurrence of
      coronary disease, strokes and arterial thrombosis. We demonstrated previously
      that adenosine inhibits TF expression in human umbilical vein endothelial cells
      (HUVECs) stimulated with inflammatory mediators. In the present study, we
      evaluated the mechanism of adenosine-induced inhibition of TF expression in
      HUVECs. The adenosine inhibitory activity on thrombin-induced TF expression in
      HUVECs was potentiated by the NO precursor, l-arginine, but it was significantly
      suppressed by the NO scavenger, 2(4-carboxyphenyl)-4,4,5,5-tetramethyl
      imidazoline-1-oxyl-3-oxide, and by endothelial NO synthase inhibitors, N(G)
      monomethyl-l-arginine and N(G)-nitro-l-arginine methyl ester, in a dose-dependent
      manner. The concentrations of nitrites, cGMP and cAMP in the culture medium of
      HUVECs treated with a mixture of thrombin and adenosine were significantly higher
      compared with the culture medium of HUVECs treated with thrombin alone. Northern
      blotting showed that thrombin decreases and adenosine increases the eNOS mRNA
      expression in HUVECs. A cAMP-dependent protein kinase inhibitor suppressed NO
      mediated TF inhibition in a dose-dependent manner. Overall, these results suggest
      that adenosine inhibits thrombin-induced TF expression in endothelial cells by a
      NO-mediated mechanism, and that increased intracellular formation of cAMP is
      implicated in this inhibitory activity of NO.

PMID- 11834137
TI  - Determinants of brachial artery mean 24 h pulse pressure in individuals with Type
      II diabetes mellitus and untreated mild hypertension.
AB  - Brachial artery pulse pressure is a predictor of (cardiovascular) morbidity, but
      its determinants in individuals with Type II diabetes and untreated mild
      hypertension have not been elucidated. We therefore cross-sectionally
      investigated determinants of brachial artery mean 24 h pulse pressure in 60
      individuals (40 males; age, mean +/- S.D., 57.8 +/- 7.5 years) with Type II
      diabetes [median diabetes duration (interquartile range), 6.3 (3.6-10.1) years]
      and untreated mild hypertension [sitting blood pressure >140/90 mmHg and <190/120
      mmHg (mean of two consecutive auscultatory office measurements after 5 min of
      rest)]. We measured (1) three potential determinants reflecting different aspects
      of central artery stiffness [the overall systemic arterial compliance, the aortic
      augmentation index and 1/(regional carotido-femoral transit time)], (2)
      structural and functional changes of the circulatory system often observed in
      Type II diabetes, and (3) diabetes-associated metabolic variables. After
      adjustment for age, gender and mean arterial pressure, brachial artery pulse
      pressure was associated with autonomic function [standardized regression
      coefficient (beta), -0.27 (P=0.01)], blood pressure decline during sleep
      [standardized beta, -0.32 (P=0.002)], fasting glucose concentration [standardized
      beta, 0.26 (P=0.01)], HbA(1c) concentration [standardized beta, 0.27 (P=0.003)]
      and diabetes duration [standardized beta, 0.28 (P=0.002)] in linear regression
      analyses. In a combined multivariate model, brachial artery pulse pressure was
      independently determined by gender [1=male, 2=female; standardized beta, 0.24
      (P=0.01)], diabetes duration [standardized beta, 0.18 (P=0.03)], mean arterial
      pressure [standardized beta, 0.32 (P=0.002)], systemic arterial compliance
      [standardized beta, -0.23 (P=0.02)] and fasting glucose concentration
      [standardized beta, 0.20 (P=0.02)]. Aortic augmentation index and 1/(carotido
      femoral transit time) were not independently associated with pulse pressure. In
      conclusion, in individuals with Type II diabetes and untreated mild hypertension,
      brachial artery pulse pressure is determined mainly by proximal aortic stiffness
      in a way which is not strongly influenced by peripheral pulse wave reflection.
      Approx. 60% of the variance in brachial artery pulse pressure could be explained
      by potentially modifiable determinants.

PMID- 11834138
TI  - Vascular endothelial growth factor and its receptor, Flt-1, in the plasma of
      patients with coronary or peripheral atherosclerosis, or Type II diabetes.
AB  - Since atherosclerosis is characterized by endothelial damage, re-growth seems
      likely to be occurring in order to repair or replace injured cells. Angiogenic
      vascular endothelial growth factor (VEGF), a likely mediator of these events,
      acts on the endothelium via a specific receptor, Flt-1. We hypothesized that
      patients with different manifestations of atherosclerosis, and others with
      diabetes, would have altered plasma levels of VEGF and Flt-1 compared with
      healthy individuals. Accordingly, 70 patients with peripheral artery disease
      (PAD), 70 patients with coronary artery disease (CAD), and 70 age- and sex
      matched healthy controls were recruited. We also recruited 14 patients with
      diabetes asymptomatic for atherosclerosis, 14 patients with diabetes and
      atherosclerosis, and 14 age- and sex-matched controls. VEGF and soluble Flt-1
      (sFlt-1) were measured by ELISA. In the main study of PAD and CAD, VEGF was
      raised in both patient groups (P<0.05) compared with the controls, but was not
      different between the patient groups. sFlt-1 was lower in patients with PAD
      (P<0.05), but not in those with CAD, compared with the controls. VEGF was raised
      in the patients with diabetes plus atherosclerosis (P<0.05), but not in the group
      with diabetes alone; levels of sFlt-1 were unaltered in both diabetes groups. Our
      data point to changes in plasma levels of VEGF and its receptor sFlt-1 in
      diabetes and atherosclerosis that may have relevance for therapy and angiogenesis
      in these conditions.

PMID- 11834139
TI  - Regular ingestion of black tea improves brachial artery vasodilator function.
AB  - A higher intake of black tea has been associated with lower cardiovascular
      disease risk. The antioxidant effects of tea polyphenols may enhance endothelial
      function and thereby reduce the risk of coronary events. The objective of the
      present study was to determine whether regular ingestion of black tea can improve
      brachial artery vasodilator function. The effects of regular ingestion of 5 cups
      per day of black tea for 4 weeks were compared with control conditions (hot water
      ingestion) in 21 subjects with mild elevations in serum cholesterol or
      triacylglycerol (triglyceride) concentrations in a parallel designed study.
      Endothelial function of the brachial artery was assessed ultrasonographically by
      measurement of post-ischaemic (endothelium-dependent) dilatation of the brachial
      artery. Endothelium-independent dilatation of the brachial artery was measured
      following administration of 400 microg of sublingual glyceryl trinitrate. Regular
      ingestion of black tea resulted in a significant and consistent increase in
      endothelium-dependent dilatation (2.3%; P=0.008) and in a significant increase in
      endothelium-independent dilatation (4.2%; P=0.03), compared with ingestion of hot
      water. These differences remained after adjustment for age, sex and body mass
      index. These results suggest that one mechanism by which black tea may reduce
      cardiovascular risk is via improved vasodilator function of conduit arteries.

PMID- 11834140
TI  - Effect of glycyrrhetinic acid on 11 beta-hydroxysteroid dehydrogenase activity in
      normotensive and hypertensive subjects.
AB  - The 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) isoenzymes catalyse the
      interconversion of cortisol and cortisone. Type 1 11 beta-HSD mainly converts
      cortisone into active cortisol. Type 2 11 beta-HSD inactivates cortisol in
      mineralocorticoid target tissues, and its activity can be inhibited by
      glycyrrhetinic acid (GA). Inactivation of cortisol to cortisone is impaired in a
      subgroup of patients with primary hypertension. To study where this defect is
      located, we measured cortisol and cortisone concentrations in arterial plasma, in
      saliva and across the forearm at baseline and after administration of GA in
      normotensive and hypertensive subjects. GA (500 mg) or placebo was administered
      orally to 20 normotensive subjects in a placebo-controlled double-blind fashion.
      Further, we compared the effect of GA in 20 patients with primary hypertension
      with that in 20 normotensive subjects. Cortisol and cortisone were measured in
      plasma from the brachial artery and vein and in saliva. Samples were obtained at
      0, 90 and 150 min. Forearm blood flow (FBF) was measured simultaneously. Forearm
      production of corticosteroid hormones was assessed by multiplying the
      arteriovenous difference in corticosteroid concentration by FBF. The
      cortisol/cortisone ratio in arterial plasma remained at baseline levels after
      placebo (4.9 +/- 1.2; mean +/- S.D.), while after GA the ratio increased
      similarly in normotensive subjects (12.3 +/- 3.4) and in hypertensive patients
      (12.2 +/- 3.7). A similar effect of GA on the salivary cortisol/cortisone ratio
      was found. In both normotensive subjects and hypertensive patients no forearm
      production of cortisol or cortisone could be demonstrated, either at baseline or
      after administration of GA. Thus, both before and after GA administration, we did
      not find any difference in systemic and salivary 11 beta-HSD type 2 activity
      between subjects with primary hypertension and normotensive controls. Further,
      both at baseline and after GA administration we were not able to demonstrate net
      inactivation or re-activation of cortisol and cortisone by the 11 beta-HSD
      isoenzymes in the forearm in either normotensive or primary hypertensive
      subjects.

PMID- 11834141
TI  - Nitric oxide and renal and cardiac dysfunction in cirrhosis.
AB  - Nitric oxide (NO) has diverse physiological and pathophysiological effects. The
      roles of NO in the renal and cardiac dysfunction found in cirrhosis are reviewed.
      In the kidneys of experimental animals with cirrhosis, several lines of evidence
      speak in favour of an enhanced production of NO, through the activation of both
      endothelial constitutive and inducible isoforms of NO synthase. In contrast with
      the situation in normal animals, inhibition of NO synthesis in rats with
      cirrhosis improves sodium and water excretion via blood pressure-dependent and 
      independent mechanisms, which indicates that the renal sodium and water retention
      of cirrhosis is related to an excess of NO production. The deleterious effect of
      excessive NO on the kidney may be mediated by peroxynitrite, a potent oxidant
      that is readily formed whenever superoxide anions and the *NO radical are
      produced together. The peroxidation of arachidonic acid by peroxynitrite leads to
      the formation of F(2a)-isoprostanes, which are powerful renal vasoconstrictors.
      F(2a)-isoprostane levels are correlated with the severity of liver injury during
      cirrhosis. However, whether peroxynitrite or F(2a)-isoprostanes are the elusive
      mediator of the NO-induced renal alterations in cirrhosis remains to be firmly
      established. NO is also involved in cardiac contractility, probably in the normal
      heart as well as in disease conditions such as non-cirrhotic and cirrhotic
      cardiomyopathy. In the latter state, evidence suggests that inducible NO synthase
      attenuates ventricular contractility, mediated by cGMP. Another gas that
      transduces its signal through cGMP, carbon monoxide, is also likely to play a
      role in cirrhotic cardiomyopathy, but the nature of the interaction between NO
      and carbon monoxide in this syndrome remains unclear.

PMID- 11834142
TI  - Are the reductions in triacylglycerol and insulin levels after exercise related?
AB  - Moderate exercise improves insulin sensitivity and reduces triacylglycerol
      (triglyceride; TG) concentrations. We hypothesized that changes in insulin
      sensitivity are an important determinant of exercise-induced changes in
      postprandial TG concentrations. Altogether, 38 men and 43 women, all of whom were
      normotriglyceridaemic and normoglycaemic, each underwent two oral fat tolerance
      tests with different pre-conditions: control (no exercise) and prior exercise (90
      min of exercise at 60% of maximal O(2) uptake the day before). Venous blood
      samples were obtained in the fasting state and for 6 h after a high-fat mixed
      meal. In the control trial there were significant correlations between log
      fasting TG concentration and log fasting insulin concentration (r=0.42, P<0.0005)
      and between log postprandial TG response (area under the curve) and log
      postprandial insulin response (r=0.48, P<0.0005). Prior exercise reduced the
      fasting TG concentration by 18.2 +/- 2.2% (mean +/- S.E.M.) (P<0.0005), the
      postprandial TG response by 21.5 +/-1.9% (P<0.0005), the fasting insulin
      concentration by 3.8 +/- 3.1% (P<0.01) and the postprandial insulin response by
      11.9 +/- 2.5% (P<0.0005). However, there was no relationship between the exercise
      induced changes in log fasting TG and log fasting insulin (r=0.08, P=0.50), nor
      between the exercise-induced changes in log postprandial TG response and log
      postprandial insulin response (r=0.04, P=0.70). These data suggest that the
      reductions in fasting and postprandial TG levels elicited by a session of
      moderate-intensity exercise are not mediated by an increase in insulin
      sensitivity.

PMID- 11834143
TI  - Holmium as a faecal marker for copper absorption studies in adults.
AB  - The objective of the present study was to investigate the validity of using
      holmium as a faecal marker in a copper absorption study using a highly enriched
      (65)Cu stable isotope label. Ten volunteers (nine female, one male) aged 24-55
      years were recruited from the Norwich area to take part in a free-living study.
      The study was conducted in the Human Nutrition Unit at the Institute of Food
      Research, Norwich, U.K., and involved feeding breakfast test meals containing
      foods labelled intrinsically or extrinsically with a highly enriched (65)Cu
      stable isotope label. A 1 mg oral dose of the rare earth element holmium was
      administered to volunteers simultaneously with an oral dose of highly enriched
      (65)Cu stable isotope as a label in the breakfast test meal. Complete faecal
      collections were made for 10 days after dosing, and the mean percentage holmium
      recovery (+/- S.D.) was 105 +/- 15%. After correcting for re-excreted copper
      label, the labelled copper and holmium had similar excretory profiles. It was
      concluded that holmium is a valid faecal marker in adult human copper absorption
      studies using stable isotopes.

PMID- 11834144
TI  - Insulin-mediated vasodilatation, but not glucose uptake or endothelium-mediated
      vasodilatation, is enhanced in young females compared with males.
AB  - In order to evaluate possible differences between men and women with regard to
      the ability of insulin to induce vasodilatation, promote glucose uptake and
      enhance endothelium-dependent vasodilatation, 12 young (22-28 years), non-obese
      women and 15 corresponding males were subjected to 2 h of euglycaemic
      hyperinsulinaemia (insulin infusion rate of 56 m-units x min(-1) x m(-2)).
      Forearm blood flow was measured by venous occlusion plethysmography. Endothelium
      dependent vasodilatation was evaluated by the local intra-arterial infusion of
      methacholine into the brachial artery (2-4 microg/min). The cardiac index was
      measured by thoracic bioimpedance. A 2 h period of hyperinsulinaemia increased
      the plasma insulin concentration to a similar degree in both sexes (females, 84
      +/- 8.8 m-units/l; males, 87 +/- 7.5 m-units/l), but induced a more marked
      increase in forearm blood flow in females than in males (+104 +/- 67% and +52 +/-
      30% respectively; P<0.01; 95% confidence interval for difference 11-94%).
      Furthermore, a significant decrease in total peripheral resistance (-20 +/- 6.9%;
      P<0.01) and an increase in cardiac index (+23 +/- 13%; P<0.01) were seen in women
      only (P<0.05 compared with men). Blood pressure and heart rate were not altered
      in either sex. Whole-body insulin-mediated glucose uptake and forearm glucose
      uptake did not differ between the sexes, and the ability of insulin to enhance
      endothelium-dependent vasodilatation (+19%; P<0.01) was similar in men and women.
      In conclusion, the present study shows that the ability of insulin to cause
      vasodilatation was greater in non-obese young women compared with men. However,
      no differences between the sexes were seen with regard to insulin-mediated
      glucose uptake and the ability of insulin to enhance endothelium-dependent
      vasodilatation.

PMID- 11834145
TI  - Non-invasive measurement of cardiac output in heart failure patients using a new
      foreign gas rebreathing technique.
AB  - Values of effective pulmonary blood flow (Q(EP)) and cardiac output, determined
      by a non-invasive foreign gas rebreathing method (CO(RB)) using a new infrared
      photoacoustic gas analysing system, were compared with measurements of cardiac
      output obtained by the direct Fick (CO(FICK)) and thermodilution (CO(TD)) methods
      in patients with heart failure or pulmonary hypertension. In 11 patients, of
      which three had shunt flow through areas without significant gas exchange, the
      mean difference (bias) and limits of agreement (+/- 2 S.D.) were 0.6 +/- 1.2
      litre x min(-1) when comparing CO(FICK) and Q(EP), and -0.8 +/- 1.3 litre x min(
      1) when comparing CO(FICK) and CO(TD). When correction for intrapulmonary shunt
      flow was applied (i.e. calculation of CO(RB)) in all 11 patients, the bias
      between CO(FICK) and CO(RB) was 0.1 +/- 0.9 litre x min(-1), primarily because
      agreement improved in the three patients with significant shunt flow. In the
      eight patients without significant shunt flow, the agreement between Q(EP) and
      CO(FICK) was 0.3 +/- 0.9 litre x min(-1). In conclusion, a foreign gas
      rebreathing method with a new infrared photoacoustic gas analyser provided at
      least as reliable a measure of cardiac output as did thermodilution. In the
      absence of significant shunt flow, measurement of Q(EP) itself provides a
      reliable estimate of cardiac output in heart failure patients. The infrared
      photoacoustic gas analyser markedly facilitates clinical use of the rebreathing
      method in general, which makes the method available to a larger group of
      clinicians working with patients with cardiovascular diseases.

PMID- 11834146
TI  - Peri-operative treatment of most severely head-injured patients.
AB  - OBJECTIVE: To summarize the peri-operative experience from 53 patients with
      traumatic head injuries with GCS score 3-5. METHODS: Fifty-three most severely
      head-injured patients with GCS score 3-5 were admitted to our department and
      treated operatively from Oct. 1994 to Jun. 1998 and the data were analyzed
      retrospectively. RESULTS: Thirty-seven cases (69.8%) survived, among them 28
      (52.8%) had a good recovery or moderate disability, and 9 (17%) had severe
      deficits. The other 16 (30.2%) died after therapy. CONCLUSIONS: The prognosis of
      most severely head-injured patients could be improved by peri-operative treatment
      including premedical care, early evacuation of intracranial hematoma with large
      decompressive craniectomies, intracranial hypertension monitoring, moderate
      hypothermia therapy, effective prevention and treatment of cerebral vasospasm and
      complications.

PMID- 11834147
TI  - Ocular histopathological changes after eyeball enucleation induced by corneal
      trauma.
AB  - OBJECTIVE: To observe the ocular histopathological changes after eyeball
      enucleation induced by corneal trauma. METHODS: Light microscopic examination was
      done on 117 eyeball specimens enucleated after corneal trauma (18 with corneal
      fissure and 99 with corneal perforating trauma). RESULTS: Acute, subacute or
      chronic inflammatory changes, and fibrous membrane formation were observed in
      well-closed corneal wounds, whereas inflammation, atrophy and scar were observed
      in the focal tissues. But at the late period, secondary glaucoma, retinal
      detachment, endophthalmitis and eyeball atrophy resulted in blindness. Corneal
      fistula was observed in those with inadequate cure of wounds caused by ingrowth
      of corneal epithelium, embedment of iris and vitreous body, and large area of
      centrally located tissue deficiency of the corneal. A high incidence of
      endophthalmitis was noted due to the presence of corneal fistula. Severe
      inflammation was observed in the anterior segmental tissues with fibrous
      infiltration in the anterior chamber, which might result in rapid destruction of
      the eyeballs. CONCLUSIONS: Ocular pathology varies with the difference of the
      position, form, size and closing conditions of the corneal laceration after
      trauma.

PMID- 11834148
TI  - Regulative effect of P38MAPK on release of TNFalpha and NO from alveolar
      macrophages under endotoxin stimulation.
AB  - OBJECTIVE: To evaluate activation of P38 mitogen-activated protein kinase
      (P38MAPK) in alveolar macrophage (AM), release of TNFalpha and NO from cells, and
      their relationship following lipopolysaccharide (LPS) stimulation. METHODS: AM
      was isolated from branch alveolar lavage fluid (BALF). The activation of P38MAPK
      was assayed by Western blot. SB203580, a specific inhibitor of P38MAPK, was used
      with gradient concentration to evaluate the regulative effect of P38MAPK on the
      release of TNFalpha and NO from AM. RESULTS: P38MAPK was activated by LPS (100
      ng/ml) with peak activation at 30 minutes. The activation of P38MAPK was
      inhibited by SB203580. The secretion of TNFalpha and NO stimulated with LPS
      increased (P<0.01) and was inhibited by SB203580 significantly. CONCLUSIONS: The
      results indicate that P38MAPK is involved in the secreting process of TNFalpha
      and NO following LPS stimulation. P38MAPK may be an important site for
      controlling the secretion of both inflammatory mediators during lung inflammatory
      disorders.

PMID- 11834149
TI  - The role of radiocarpal injection arthrography and magnetic resonance imaging in
      the diagnosis of triangular fibrocartilage complex injuries.
AB  - OBJECTIVE: To investigate the radiocarpal joint injection arthrography and
      magnetic resonance imaging for diagnosis of the triangular fibrocartilage complex
      (TFCC) injuries. METHODS: Thirteen cases whose main complaints were ulnar wrist
      pain were given radiocarpal joint arthrography and eight of them were also given
      magnetic resonance imaging for evaluating the integrity of the triangular
      fibrocartilage complex. RESULTS: Ten of thirteen cases presented the leakage of
      contrast medium to distal radioulnar joint from the radiocarpal joint, in whom, 8
      were demonstrated triangular fibrocartilage tear on magnetic resonance imaging,
      and 3 located at radial side, 2 at central, 3 at ulnar side. One of three cases
      which were demonstrated without the leakage of contrast medium in arthrography
      were displayed with marked TFCC tear on magnetic resonance imaging. CONCLUSIONS:
      The wrist arthrography can provide a definite diagnosis for triangular
      fibrocartilage disruption with higher sensitivity. magnetic resonance imaging not
      only demonstrates the site of triangular fibrocartilage disruption as the same
      value as wrist arthrography, but also displays the other related bony and soft
      tissues changes.

PMID- 11834150
TI  - Clinical application of tentorium cerebelli hiatus incision in treatment of
      severe and most severe brain injuries.
AB  - OBJECTIVE: To explore the role of tentorium cerebelli hiatus incision in treating
      severe and most severe brain injuries complicated by tentorial herniation.
      METHODS: From July 1994 to July 1999 tentorium cerebelli hiatus incision was done
      based on intracranial hematoma evacuation and bone flap craniectomy decompression
      in 70 cases of severe and most severe brain injuries complicated by tentorial
      herniation. RESULTS: Of the 70 cases, GCS 3-5 was in 23 and GCS 6-8 in 47;
      satisfactory recovery in 39 cases (55.7%), moderate disability in 12 (17.1%),
      severe deficit in 6 (8.6%), vegetative survival in 4 (5.7%) and 8 (11.4%) died.
      CONCLUSIONS: Tentoriun cerebelli incision is helpful in alleviating secondary
      brain stem injury from tentorial herniation and in reducing the disability and
      death rate of the patients.

PMID- 11834151
TI  - Signal transduction pathway of nitric oxide inducing PC12 cell death.
AB  - OBJECTIVE: To study signal transduction pathway of nitric oxide inducing death of
      PC12 cells. METHODS: Cell survival rate was measured with MTT assay, and caspase
      3 activity with caspase-3 assay kits after PC12 cells were incubated with sodium
      nitroprusside (SNP), caspase-3 inhibitor II plus SNP or p38 inhibitor-SB203580
      plus SNP. RESULTS: SNP induced death of PC12 cells in dose- and time-dependent
      manner and enhanced caspase-3 activity gradually. Both caspase-3 inhibitor II and
      SB203580 reduced cell death, but SB203580 reduced caspase-3 activity
      significantly. CONCLUSIONS: NO may induce death of PC12 cells through activation
      of p38 and caspase-3.

PMID- 11834152
TI  - Changes of blood circulation of the extremity after external fixation for tibia
      shaft defect: an experimental study.
AB  - OBJECTIVE: To assess and compare two approaches, end to end compression with
      lengthening (EECL) and segmental bone transport by lengthening (STBL), for long
      tubular bone defect and nonunion. METHODS: Ten goats were used to establish the
      bone defect model of the mid-tibia. The bone defect ends were shortened step by
      step with a sulcated half-ring external fixator. Changes of the blood flow of the
      distal extremity were measured with pulse-Doppler monitor and angiography.
      RESULTS: The blood flow in the distal extremity was not affected when bone defect
      was less than 15% of the original length. Blood circulatory disorder would appear
      in the distal extremity when bone defect ranged 15%-20% of the original length.
      The necrosis would appear in the extremity because of the blood circulatory
      obstacle when bone defect was more than 20% of the original length. CONCLUSIONS:
      EECL is an appropriate alternative of treatments if bone defect is less than 15%;
      while SBTL may be feasible if bone defect is over 20% of the original length.
      When bone defect ranges between 15% and 20%, EECL should be applied with great
      care on condition of keeping watch on the extremity circulation with pulse
      Doppler monitor.

PMID- 11834153
TI  - Prospective survey on neurosurgical intensive care for patients with severe head
      injury.
AB  - OBJECTIVE: To prospectively compare the clinical outcome of intensive care
      therapy (ICT) with that of conventional care therapy (CCT) in severe head injured
      patients. METHODS: Patients with severe head injury were assigned randomly into
      Group ICT and Group CCT, 100 patients in each group. Patients in Group ICT
      accepted intensive care therapy in neurosurgical intensive care (NIC) unit for
      the first 2 weeks after admission, while patients in Group CCT accepted
      conventional care therapy in ordinary ward. The outcomes were evaluated 3 months
      after injury. RESULTS: There was a significant increase in good recovery (54%)
      (chi(2)=4.43, P<0.05) and significant decrease of death (25%) (chi(2)=4.50,
      P<0.05) in Group ICT compared to 39% and 39% in Group CCT respectively. The
      differences were also confirmed statistically in the following aspects: the
      patients under 50 years with good recovery pronounced a number increase
      (chi(2)=7.54, P<0.01), while the mortality in the same range of age was decreased
      in Group ICT (chi(2)=5.28, P<0.05). The mortality was reduced significantly in
      patients with GCS for 6-8 on admission (chi(2)=8.47, P<0.01) and in patients with
      the level of brain stem injured below mesencephalon (chi(2)=4.15, P<0.05). ICT
      would improve the outcome in patients undergoing conservative therapy only
      (chi(2)=13.13, P<0.01). CONCLUSIONS: NIC plays an important role in assessing the
      neurological state, guiding management, evaluating curative effect and estimating
      the outcome.

PMID- 11834154
TI  - Observation of wounding characteristics in dogs wounded by super velocity
      projectile.
AB  - OBJECTIVE: To understand wounding characteristics in dogs wounded by super
      velocity projectile with a purpose of providing a basis for prevention and
      treatment of such wounds. METHODS: A specially-made explosive gun was used to
      shoot aluminium bullet weighing 3.0 g and 1.4 g to injure both legs of dogs at
      velocities of 2330 m/s, 3200 m/s and 4250 m/s, respectively, and the soap
      specially made was also shot. At the same time, steel ball of 1.03 g was shot
      with a Type 53 smooth chamber gun at a speed of 1280 m/s. Within 30 min after
      wounding, debridement and pathological anatomy were performed and specimens were
      taken for light microscope observation. RESULTS: When the dogs were wounded by
      the 3 g bullet at speed of 2330 m/s, the entrance of the left leg was penetrated
      explosively with a defect area of 225 cm(2), and the femur trunk was also injured
      and the residual femur had comminution fracture. The exit of the right leg was
      blindly wounded with a defect area of 63 cm(2), but only the skin was not
      penetrated. Both testes and part pelvis were injured too. Under light microscope,
      degenerative myofibers and bleeding of the spatium between the myofibers could be
      found at the place 4 cm away from the wounding track. Furthermore, serious
      bleeding of the bladder and blood vessels of the brain could be observed. The
      lungs showed changes of blast injury. Vacuolar change was presented in the
      cytoplasm of hepatocytes. Injuries of the animals in other two experimental
      groups were similar to those described above, but the defect area of the wounded
      track was 124 cm(2) in the group of 4250 m/s. Injuries caused by the steel ball
      were milder than caused by the explosive gun. The volume of the residual cavity
      in the soap was 5000 ml. CONCLUSIONS: The super-velocity projectile causes
      destructive damage to the local tissues and multi-organ injuries. Therefore, the
      practical medical care needs not only amputation but also management of multi
      organ injuries.

PMID- 11834155
TI  - Effects of recombinant human growth hormone (r-hGH) on experimental osteoporotic
      fracture healing.
AB  - OBJECTIVE: To observe the effect of recombinant human growth hormone (r-hGH) on
      osteoporotic fracture healing in rats, and to provide an effective therapy for
      osteoporotic fracture. METHODS: Thirty-six female 8-month-old SD rats were
      randomized into two groups: therapy group and control group. After the
      experimental model of osteoporotic fracture was established, the therapy group
      was treated with r-hGH of 2.7 mg/kg body weigh/day (1 mg=3 IU) for 10 days
      continuously by daily subcutaneous injection; whereas the control group was
      treated with equivalent saline. Plasma insulin-like growth factor I concentration
      was detected and bone mineral density (BMD) as well as biomechanical strength of
      callus were measured at 2, 4, 8 weeks. RESULTS: Plasma insulin-like growth factor
      I concentration in the therapy group was higher than that in the control group
      (P<0.005) at 2nd week and began to decline at 4th week. At 8th week, there was no
      significant difference between the two groups. At 4th week, callus area and BMD
      in therapy group were higher than those in the control group, but at 8th week,
      they were lower and BMD had a significant difference between the two groups
      (P<0.001). Biomechanical testing of callus showed that torsional strength of the
      therapy group was higher than that of the control group at 4th or 8th week,
      meanwhile maximum torsional angle had a significant difference between the two
      groups (P<0.005). CONCLUSIONS: The results show that exogenous r-hGH can
      stimulate osteoporotic fracture healing in rats.

PMID- 11834156
TI  - Temporal bone fracture and its complications.
AB  - OBJECTIVE: To explore the characteristics and treatment of temporal bone
      fractures and injuries in the medial-inner ear. METHODS: The clinical data of 48
      cases of temporal bone fractures admitted to our hospital from January 1989 to
      November 1999 were retrospectively analyzed. RESULTS: Forty-eight patients with
      temporal bone fractures accounted for 17.00% of the homochronous craniofacial
      fractures. Of the 48 cases, temporal bone fractures induced by traffic accidents
      accounted for 66.67%, capillary fractures for 93.75%, medial  inner ear injuries
      or craniocerebral injuries for 77.08% and hearing loss or tinnitus for 48.00%.
      The cerebrospinal fluid (CSF) otorrhea and facioplegia accounted for 36.70% and
      3.00%, respectively, in the longitudinal fractures, while they were 25.00% and
      37.50%, respectively, in the transversal fractures. Primary emergent operations
      were performed on 46 cases and neurosurgery accounted for 46.00%. Secondary
      procedures accounted for 16.70%. As a result, 43 cases survived (89.58%) and 5
      died (10.41%). CONCLUSIONS: Traffic injury is the first high-dangerous factor for
      temporal bone fractures, which are often complicated with medial-inner ear or
      craniocerebral injury. The CSF otorrhea is common in the longitudinal fractures
      and facioplegia is common in the transversal fractures. The key step is to rescue
      the life, keep the airway unobstructed and maintain the circulation in the
      primary emergency treatment.

PMID- 11834157
TI  - Effects of recombinant human basic fibroblast growth factor on cell proliferation
      during mandibular fracture healing in rabbits.
AB  - OBJECTIVE: To investigate the effects of recombinant human basic fibroblast
      growth factor (rhbFGF) on the cell proliferation during mandibular fracture
      healing in rabbits. METHODS: The complex of rhbFGF and bovine type I collagen was
      implanted into the mandibular fracture site under periosteum of the animal. The
      whole mandible was harvested at 7, 14, 28, 56 and 84 days respectively after
      operation. The expression of proliferating cell nuclear antigen (PCNA) in callus
      was examined with immunohistochemical staining. RESULTS: PCNA-positive cells in
      callus in the rhbFGF-treated group on days 7 and 14 were more than that in the
      control group (P<0.01). CONCLUSIONS: It indicates that rhbFGF can stimulate cell
      proliferation during mandibular fracture healing in rabbits.

PMID- 11834158
TI  - Retinochoroidal changes after severe brain impact injury in rabbits.
AB  - OBJECTIVE: To investigate retinochoroidal changes and establish eye damage model
      after brain impact injury. METHODS: An eye damage model after brain impact injury
      was established by striking the frontoparietal zone in rabbits with BIM-II
      bioimpact machine. Seventeen rabbits were killed at 4 different intervals after
      injury. The pathological characteristics of the retinal and choroid damages were
      observed. RESULTS: All the rabbits had severe brain injury with subarachnoid
      hemorrhage and brain contusion. The eye damage occurred in all of the 17 rabbits.
      Hemorrhage in optic nerve sheaths was observed and retinal edema and bleeding was
      discovered with ophthalmoscope. Histopathologic study displayed subarachnoid
      hemorrhage in the retrobulbar portion of the retinal nerve, general choroid blood
      vessel dilatation, retinal nerve fibre swelling within 6 hours after injury, and
      flat retinal detachment with subretinal proteinoid exudation, and degeneration
      and disappearance of the outer segment of the optic cell over 6 hours after
      injury. CONCLUSIONS: The pathological characteristic of the eye damage at early
      stage following brain impact injury is local circulation disturbance. At late
      stage, it features in retinal detachment, and optic cellular degeneration and
      necrosis.

PMID- 11834159
TI  - Clinical and experimental study on facial paralysis in temporal bone fracture.
AB  - OBJECTIVE: To study the main prognostic factors and significance of facial nerve
      decompression for facial paralysis in temporal bone fracture. METHODS: The main
      relative prognostic factors of 64 patients with facial paralysis were analyzed.
      An experimental model of facial paralysis was made. The expansion rates of facial
      nerve in the facial canal opening group and the facial canal non-opening group
      were measured and observed under electron microscope. RESULTS: The main factors
      affecting the prognosis were facial nerve decompression and selection of surgery
      time. The expansion rate of facial nerve in the facial canal opening group was
      significantly higher than that of the facial canal non-opening group (t=7.53,
      P<0.01). The injury degree of the nerve fiber in the facial canal non-opening
      group was severe. CONCLUSIONS: Early facial nerve decompression is beneficial to
      restoration of the facial nerve function.

PMID- 11834160
TI  - Analysis of 133 patients with severe blunt liver injury.
AB  - OBJECTIVE: To investigate the treatment and causes of death about severe blunt
      liver injury. METHODS: The data of 133 patients with severe blunt liver injury
      (Grade III to Grade V) were analyzed retrospectively. All the patients except 2
      underwent operations. Different types of surgical procedures were adopted
      according to the severity of liver injury. RESULTS: Operations were the major
      method to treat hepatic injury. The total mortality rate was 21.0% in this study.
      The mortality rates of Grade III, Grade IV and Grade V of liver injuries were
      11.3%, 24.4% and 69.2%, respectively. CONCLUSIONS: Packing treatment plays an
      important role in the treatment of hepatic injury. The mortality rate is related
      closely to the severity of hepatic injury, multiple trauma, shock and disturbance
      of blood coagulation.

PMID- 11834161
TI  - Protective effect of ischemic preconditioning on liver.
AB  - OBJECTIVE: To study the protective effect of ischemic preconditioning (IPC) on
      the hepatic ischemia reperfusion injury. METHODS: The model of rat liver
      subjected to ischemia/reperfusion (I/R) injury was made. All 24 mice were divided
      randomly into 3 groups and anesthetized by 2% sodium pentobarbital (30-40 mg/kg).
      The enzyme activity of AST, ALT, LDH, SOD and the content of LPO were assayed
      respectively. Specimens were observed under transmission electron microscope.
      RESULTS: IPC prevented the increase of ALT, AST and LDH in the blood and that of
      LPO in the tissues (P<0.05), and maintained high level of SOD in the tissues
      (P<0.05). CONCLUSIONS: IPC has protective effect on the liver function.

PMID- 11834162
TI  - Application of inferior major bone flap craniotomy decompression in brain injury.
AB  - OBJECTIVE: To summarize the application of inferior major bone flap craniotomy
      decompression in brain injury operation. METHODS: A retrospective analysis was
      done in 218 cases with brain injuries who were admitted to our department from
      January 1995 to December 1999 and treated with the inferior major bone flap
      craniotomy decompression. RESULTS: Of 218 cases, 121 cases (55.50%) were cured
      according to GOS, 39 (18.30%) were with good recovery or moderate disability, 13
      (5.60) with severe deformity, 3 (1.40%) vegetative life, the rest 42 (19.20%)
      died after operation; no encephalocele or incarceration were found. CONCLUSIONS:
      The inferior major bone flap craniotomy decompression can remove hematoma timely
      and completely, is better than general craniotomy decompression and has a
      positive effect on brain injuries especially when bone flap is small.

PMID- 11834163
TI  - [Age changes in CT values of human major salivary glands].
AB  - OBJECTIVE: To investigate CT values ranges of normal major salivary gland in
      different age groups and regularity of age changes. METHODS: CT values of normal
      parotid and submandibular glands, comparing with those of masseter and
      sterocleidomastoid muscles, were measured and analyzed in 100 cases with 4
      different age groups. RESULTS: CT values of parotid and submandibular gland
      decreased with aging, whereas no significant age change in CT values occurred in
      the masseter and sterocleidomastoid muscles. The CT values of parotid and
      submandibular gland showed big differences in different age groups. This
      difference, however, became smaller after the case were divided in 4 groups
      reference to age. CONCLUSION: CT value ranges of normal major salivary gland
      should be determined according to the age. It is possible to take the
      contralateral gland as the control gland for CT diagnosis.

PMID- 11834164
TI  - [The study of automatic cephalometric analysis system].
AB  - OBJECTIVE: To develop a system of automatic cephalometric analysis and compare
      the reliability of the computer software systems (ACAS and OSPES). METHODS: The
      establishment of the ACAS computer software system by image processing technique
      was introduced. 15 cephalograms were used for comparing the reliability of
      cephalometry between ACAS and OSPES. RESULTS: The results shown that the ACAS is
      more reliable for soft tissue profile measurement than OSPES. CONCLUSION: The
      application of ACAS would supply a valuable measurement tool for orthodontics and
      orthognathic surgery.

PMID- 11834165
TI  - [Functional reconstruction of mandible by using vascularized fibular free flap
      and one-stage rehabilitation of the implant].
AB  - OBJECTIVE: To study the characteristics of the vascularized fibular free flap and
      the possibility of the insertion of implant at the same time. METHODS: The
      microvascular surgical procedure and implant technique were used in the treatment
      of two cases suffered from mandibular ameloblastoma. After tumor resection by
      partial mandiblectomy, graft of vascularized fibular free flap was performed with
      simultaneous insertion of 5 implant. RESULTS: One year later, the grafted bone
      was survival, the osseointegration was proceeded between the implant and grafted
      bone. The functional reconstruction of the mandible was excellent after
      prosthetic denture. CONCLUSION: This is a good approach to rehabilitate bone
      function by using vascularized fibular free flap and one-stage implant placement.

PMID- 11834166
TI  - [Evaluation of normal submandibular gland function by sialo-scintigraphy].
AB  - OBJECTIVE: To study the normal glandular function of the submandibular gland as a
      background for evaluation of changes in submandibular gland diseases. METHODS:
      The backgrounds of both submandibular area and temporal area were analyzed
      comparatively with Emission Computerized Tomography in eleven pairs of normal
      submandibular gland. RESULTS: About 2.18 times of the temporal background equals
      to submandibular area background; the Concentrate Index of normal submandibular
      gland was 1.42 +/- 0.89; the Secretory Index was (109.4 +/- 39.8)%, the Secretory
      Index Ratio and the Concentrate Index Ratio were (77.2 +/- 17.2)% and 71.0 +/-
      15.2% respectively; and the Function Index was (89.9 +/- 7.4)%. CONCLUSION: The
      use of submandibular area background and functional index to represent
      submandibular gland function is more accurate and more sensitive. Normal
      functional index can provide the basis for researching submandibular gland
      disease.

PMID- 11834167
TI  - [Analysis of the condyle in the state on the mandibular protraction by means of
      the three-dimensional finite element method].
AB  - OBJECTIVE: Studies on the stress distribution and the displacement of the
      condylar cartilage will be conducive to expound the mechanisms of mandibular
      orthodontic therapy. METHODS: The model was constructed from young man.
      Transverse sections of mandible, included TMJ, were scanned by means of CT. An
      articular disk and condylar cartilage were constructed according to their normal
      shape and elastic modulus as the same age as to current results of studies.
      Stimulate the stomotologic muscles' and ligaments' function by means of cable
      element. The model is consisting of 1364 x 2 bricks and 1954 x 2 nodes. RESULTS:
      Stimulate the mandibular protraction (advancement) was revealed: (1) Compressive
      stress widely distributed in the anterior area of condylar cartilage (-2425
      g/cm(2) - -7399 g/cm(2)). (2) Tensile stress distributed in the posterior-upper
      area (10,000 g/cm(2)). CONCLUSION: The results indicate that the mandibular
      protraction can increase the growth of mandible to treat the skeletal Class II
      malocclusion.

PMID- 11834168
TI  - [Experimental study on three-dimensional adjustable condyle prosthesis for
      reconstruction of temporomandibular joint].
AB  - OBJECTIVE: To study the possibility of reconstructing TMJ with a modified three
      dimensional adjustable condylar prosthesis (TDACP). METHODS: The modified TDACP
      was placed immediately after resection of the mandibular ramus and condyle in 3
      adult rhesus monkeys. The results were evaluated by radiography, histological and
      anatomical examinations, as well as chewing function at 3, 6, and 14 months after
      surgery. RESULTS: Through adjustment the condyle prosthesis could fit exactly,
      the functions were good, every part of the prosthesis was firm, the screws were
      osteointegrated, there was no adverse soft tissue reactions and no pathological
      changes in the TMJ of non-operated opposite condyle. Problems were: the
      distribution of fixation stress of screws was somewhat unreasonable, the downward
      sliding of the condyle was limited, there was erosion of the posterior slope of
      the glenoid fossa, and the articular disc could not keep its in situ place and
      function. CONCLUSION: The results suggests that the prosthesis needs further
      improvement.

PMID- 11834169
TI  - [Pathological changes following retrograde infusion of methyl violet in the
      parotid gland of the miniature pig].
AB  - OBJECTIVE: To investigate the pathologic changes induced by infusion of 1% methyl
      violet in the parotid gland of the miniature pig (minipig). METHODS: Methyl
      violet (either 0.6 ml, 1.0 ml, or 4.0 ml) was injected into parotid glands of
      fifteen minipigs. The parotid glands were harvested for gross and histopathologic
      study after 1 week, 2 weeks, 1 month, 3 months and 6 months. RESULTS: The
      pathological changes induced by retrograde injection of methyl violet included
      necrosis or atrophy of acinar cells and fibrosis of the gland. The ductal system
      underwent atrophic changes, and thrombotic obliteration of main duct. CONCLUSION:
      Retrograde infusion of 1% methyl violet results in complete atrophy and fibrosis
      of the parotid gland in the minipig.

PMID- 11834170
TI  - [Experimental study of osseointegrated dental implants placed into fresh
      extraction sockets in dogs].
AB  - OBJECTIVE: To investigate the better way in treating bone defects around
      implants. METHODS: 12 mongrel dogs, pure titanium implants were immediately
      inserted in the mesial roots of the second, third and fourth mandibular premolar
      sockets. The defects around implants were separately filled with demineralized
      freeze-dried bone allograft (DFDBA), demineralized freeze-dried allocancellous in
      combination with bBMP (bBMP compound bone) and nothing. RESULTS: Histologic
      observation showed that bone defects around implants were substituted by new bone
      in DFDBA group at 12 weeks and in bBMP compound bone group at 8 weeks, and also
      the osseointegration were obtained between implants and bone, but bone defects
      were only filled about 3/5 in no graft group at 12 weeks. CONCLUSION: Immediate
      implants could obtain good osseointegration if the defects around implants were
      treated properly and the right technique was used, and also the use of bBMP
      compound bone could promote obviously bone formation in defects around implants.

PMID- 11834171
TI  - [A longitudinal research on palate growth in the normal mixed dentition by three
      dimensional image analysis].
AB  - OBJECTIVE: To investigate the trait of the palate growth and to provide a method
      of three-dimensional image analysis on revealing the entire variation of palate.
      METHODS: A longitudinal study on the palate growth of 30 subjects (male 8, female
      22) with normal occlusion during mixed dentition was carried out by three
      dimensional image analysis. The observation period was from 7 to 10 years of age.
      RESULTS: During growth, the palate vaults in 16 cases (53%) descend for 1-5 mm,
      whereas, the palate vaults in 14 cases (47%) ascend for 2.6 mm at most.
      CONCLUSION: The variations of palate growth can be investigated by three
      dimensional image analysis. During growth, the palate vault may descend or
      ascend, which shows the individual differences of oronasal function.

PMID- 11834172
TI  - [Significance of expression of epidermal growth factor receptor, transforming
      growth factor beta, c-erbB-2 oncogene in myoepithelioma of salivary gland].
AB  - OBJECTIVE: To explore the effect of expression of epidermal growth factor
      receptor (EGFR), transforming growth factor beta (TGF beta), c-erbB-2 oncogene in
      myoepithelioma and malignant myoepithelioma. METHODS: 20 cases of myoepithelioma
      and 20 cases of malignant myoepithelioma were examined by immunohistochemical
      methods. RESULTS: All cases showed overexpression of EGFR and TGF beta, the
      intensity of expression didn't associate with the benignity and malignity of
      tumors. The overexpression of c-erbB-2 oncoprotein was seen in 5 cases of
      myoepithelioma and 13 cases of malignant myoepithelioma, and the cases of
      malignant myoepithelioma were stained more intense than that of myoepithelioma.
      CONCLUSION: The synergy of EGFR and TGFR beta had significant relation to the
      proliferative and differentiation processes of myoepithelial tumor. The activated
      c-erbB-2 oncogene, that is similar with EGFR in structure, plays an important
      promoting role in unrestricted progression of malignant myoepithelioma cells.

PMID- 11834173
TI  - [Effects of human BMP2 gene transfection on NIH3T3 cells in vitro].
AB  - OBJECTIVE: To elucidate the mechanism of bone morphogenetic protein (BMP) on cell
      differentiation and to provide basis for BMP gene therapy. METHODS: A phagemid
      expression vector for human BMP2 (pBK-B2) was constructed and transfected into
      the NIH3T3 cells by using Lipofect AMINE. Positive cell clones were selected with
      G-418. The stable transfection, expression and secretion of hBMP2 were determined
      by in situ hybridization, immunohistochemistry and sandwich-in ELISA methods. The
      proliferativity of the transfected cells were assayed by methabenzthiazuron (MTT)
      method. Alkaline phosphatase (ALP) and osteocalcin (OC) production were also
      measured in the transfected cells. RESULTS: The results showed that cell
      proliferation was inhibited after the transfection with hBMP2 gene. But the
      transfected cells showed increased ALP activity and OC production. CONCLUSION:
      These results indicate that BMP2 is expressed stably and efficiently in the
      NIH3T3 cells and is involved in inducing differentiation of NIH3T3 cells into
      osteoblast-like cells.

PMID- 11834174
TI  - [Expression of ICAM-1/LFA-1 in the pocket area of adult periodontitis].
AB  - OBJECTIVE: To study the expression of ICAM-1/LFA-1 in the pocket area of adult
      periodontitis. METHODS: Expressions of ICAM-1/LFA-1 in adult gingival of
      periodontitis and healthy subjects were studied by alkaline phosphorylase
      antialkaline phosphorylase technique. RESULTS: Junctional epithelium and apical
      part of sulcus epithelium expressed ICAM-1 in both adult periodontitis and
      healthy gingiva, showing an ICAM-1 gradient change with maximal staining at tooth
      aspect and weaker staining in the basal layer of keratinocytes. Significantly
      more LFA-1 positive leukocytes were observed in connective tissues and within
      pocket epithelium in adult periodontitis than those in healthy gingiva.
      CONCLUSION: ICAM-1/LFA-1 may provide important adhesion pathway for leukocytes
      migration into gingiva sulcus in adult periodontitis lesions.

PMID- 11834175
TI  - [Effect of monoclonal antibody on the colonization of Streptococcus sobrinus and
      the development of dental caries in rats].
AB  - OBJECTIVE: To investigate the effect of local application of monoclonal antibody
      (McAb) raised against the major cell surface protein antigen of streptococcus
      sobrinus (PAg) on the colonization of rats' teeth by Streptococcus sobrinus (S.
      sobrinus) and the development of dental caries. METHODS: 30 wistar rats were
      divided into three groups: group I received McAb against PAg; group II received
      unrelated mice ascites; group III received PBS. They were applied on six
      occasions. After three times of application, streptomycin resistant S. sobrinus
      6715 were inoculated onto the teeth and the rats were fed with caries-inducing
      diet 2000#. The number of colonized S. sobrinus were counted and the presence of
      caries was examined by the procedure of Keyes'. RESULTS: There was a significant
      lower level of colonization by S. sobrinus and lower mean caries scores treated
      with McAb compared with the control groups. CONCLUSION: Local passive
      immunization with McAb against PAg may be an effective way to prevent the
      colonization by implanted S. sobrinus and the development of dental caries.

PMID- 11834176
TI  - [The isolation and characterization of dentin phosphoprotein from human dentine].
AB  - OBJECTIVE: To establish the method of isolation and characterization of dentin
      phosphoprotein (DPP) from human dentine. METHODS: Dentin powder was placed in
      dialysis tube after demineralized to completion with 0.6 mol/L HCl, then isolated
      DPP through DEAE-Sepharose CL6B anion exchange chromatography. Its protein
      composition, organic phosphorus content, molecular weight and amino acid were
      analyzed. RESULTS: DPP contained high organic phosphorus, 23.8% of aspartic
      residue and 19.1% serine residue; their molecular weight were 141, 000, 124, 000,
      108, 000 respectively. CONCLUSION: DPP can be extracted from human dentine with
      0.6 mol/L HCl demineralization. and DEAE-Sepharose CL6B anion exchange
      chromatography. It is a group of proteins which have a high content of organic
      phosphorus and is found to be rich in serine and aspartic acid residues.

PMID- 11834177
TI  - [Study on relationship of different thickness and opaquing capacity of various
      opaques].
AB  - OBJECTIVE: To evaluate the relation between different opaque thickness and color
      difference. METHODS: Model made of the thin plastic paper was used to control the
      ceramic thickness. The data of chromaticity was measured by TC-PIIG auto color
      difference meter and its results were processed by computer. RESULTS: There are
      two thickness values which can be considered as ideal range of opaque thickness
      for color opaquing: one is the values of ceramic thickness which is based on the
      color difference values of the infinite chromaticity thickness (ICT) and the
      other is the values of ceramic thickness which is depended on the color
      difference values which is 1.5 compared with ICT. The ideal range for VITA is
      (0.207-0.152) mm, SHOFO is (0.190-0.160) mm, CARAT is (0.140-0.074) mm and
      EXCELCO is (0.169-0.144) mm. CONCLUSION: There is a relationship of non linear
      direct ratio between opaque thickness and its shadow capacity. However, no more
      increase of color difference values in respect to the thickness was found when
      the ceramic thickness reach a certain value. Different ceramic porcelain needs
      different ideal range of thickness.

PMID- 11834178
TI  - [The study on mechanical properties of laser welds of titanium in dentistry].
AB  - OBJECTIVE: To explore the mechanical properties of laser welds of titanium under
      different conditions. METHODS: Home-made Nd: YAG laser welding apparatus was used
      to weld TA2 and Ti-6Al-4V under different laser energy. Instron universal testing
      machine was adopted to measure the tensile load, 0.2% yield load and absolute
      elongation. The fractured surface was observed under SEM, Vickers microhardness
      values at welding area were measured and the mechanical properties after
      immersion in artificial saliva were detected. RESULTS: The mechanical strength of
      laser welds were related with material, voltage and the combination of them. At
      700V-750V, there was no significant difference between tensile load of TA2 laser
      welds and that of the original material. For Ti-6Al-4V, At 750V. The mechanical
      strength of laser welds before and after immersion in artificial saliva made no
      statistic difference. CONCLUSION: It is suggested that the heat-affected zone of
      laser welding might be small and the corrosion resistance in artificial saliva
      might be high. The mechanical strength of titanium laser weld might meet the
      clinical demands at 19-20J/P.

PMID- 11834179
TI  - [Two years clinical observation of a kind of castable ceramic--IPS Empress].
AB  - We used this material in clinic since 1995. OBJECTIVE: Discussion on the
      prosthetic effects of the above-mentioned material to spreat it clinically.
      METHODS: Through half to two years clinical observations to evaluate the effect
      of IPS Empress crowns in anterior teeth and inlays in posteriors. RESULTS: and
      CONCLUSION: Prosthesis made of this kind of material IPS Empress is one kind of
      excellent all-ceramic prosthetic material. IPS Empress also could be used in post
      crowns and the clinical effect was satisfactory.

PMID- 11834180
TI  - Asthma treatment: improving efficacy. Reducing costs.

PMID- 11834181
TI  - Inhibition of enteropathogenic Escherichia coli (EPEC) adherence to HEp-2 cells
      by bovine colostrum and milk.
AB  - BACKGROUND: enteropathogenic Escherichia coli (EPEC) is the main etiological
      agent of infantile diarrhea in Brazil and other developing countries. Human milk
      IgA protects newborn intestinal mucosa by inhibiting bacterial adhesion to
      epithelial cells and this effect is shown by in vitro assays of EPEC adhesion to
      HEp-2 cultured cells. Bovine milk, if effective in promoting this protection,
      could be an useful tool in the absence of the natural breastfeeding, in high-risk
      nurseries or in hospital infections. METHODS: the effect of colostrum, milk, and
      serum from dairy cows on the adherence to EPEC to HEp-2 cells was investigated.
      Colostrum from immunized and control animals and industrialized milk formulas
      were fractionated through a membrane device with a molecular weight cut off 10
      kDa. The high molecular weight fraction (HMWF) of bovine colostrum was depleted
      of IgG through an affinity column and absorbed with an EPEC adherent strain.
      Antibodies were searched by ELISA and immunoblotting (IB). RESULTS: colostrum and
      milk from EPEC-immunized animals showed and inhibitory activity on adherence
      similar to that of control non-immunized animals. The inhibitory effect on
      adhesion was related to the HMWF. IgG-depleted colostrum partially retained the
      inhibitory effect, whereas IgG-rich eluate lost this property. The EPEC-absorbed
      fraction retained the inhibitory property. Industrialized milk formulas and
      respective HMWF also inhibited bacterial adherence. In IB assays, colostrum and
      milk samples from immunized animals recognized proteins of 30-40 kDa and 94 kDa,
      a molecular weight consistent with the adhesin intimin, in EPEC extracts.
      CONCLUSIONS: the inhibitory effect of EPEC adherence may be mediated by HMWF
      components, and IgG was not the only component responsible for this phenomenon.

PMID- 11834182
TI  - Efficacy of sublingual specific immunotherapy in Cupressaceae allergy using an
      extract of Cupressus arizonica. A double blind study.
AB  - BACKGROUND: non-injective routes of immunotherapy in respiratory allergy have
      being proposed as an alternative to conventional immunotherapy. We carried out a
      study to evaluate the clinical efficacy and effects sublingual immunotherapy
      (SLIT) in patient with Cupressaceae pollen respiratory allergy. METHODS: twenty
      patients with Cupressaceae pollen (C. sempervirens) rhinoconjunctivitis, mild
      asthma or both were randomly chosen for sublingual immunotherapy (10 patients) or
      placebo treatment (10 patients) using a double blind placebo controlled
      technique. We have used an extract of Cupressus arizonica because of its better
      stability in solution and its crossreactivity with Cupressus sempervirens. The
      patients underwent treatment for 12 months (from april 1999 to april 2000).
      Symptoms and drug scores as well as nasal provocation tests were recorded. The
      pollen counts were carried out, during all the same period. RESULTS: we found
      significantly lower symptom scores (p < 0.05) and drug consumption scores (p <
      0.05) in the immunotherapy group than in the placebo group, during the pollen
      season, after the first year of therapy. Besides threshold of allergen reactivity
      in nasal provocation tests was increased in the active group (p < 0.01). No
      untoward reactions have been observed. CONCLUSIONS: SLIT with Cupressus arizonica
      (pollen extracts) produced, after one year treatment, a significant improvement
      of allergic symptoms and a decrease of drug consumption scores and allergen
      specific nasal reactivity. SLIT with Cupressus arizonica appeared to be effective
      and safe in the treatment of Cupressaceae pollen respiratory allergy.

PMID- 11834184
TI  - Specific and non-specific nasal provocation tests in children with perennial
      allergic rhinitis.
AB  - BACKGROUND: nasal provocation tests (NPT) have been extensively used in clinical
      practice to evaluate chronic rhinopathies, mainly allergic rhinitis (AR).
      METHODS: we submitted 10 perennial AR children (aged from six to 15 years) to
      histamine (H), Dermatophagoides pteronyssinus (Dp) and Blomia tropicalis (Bt)
      NPT. All children were sensitized (positive skin prick test, mean wheal > 3 mm)
      to both mites. Dp and Bt specific NPT were realized in two occasions, apart one
      week, always preceeded 24 hours by H challenge. Increased concentrations were
      applied to the nasal mucosa during each NPT: H (0,03 to 16 mg/ml), Dp (1/100,000
      to 1 /2.5) and Bt (1/125,000 to 1/10). NPT were evaluated by clinical and
      rhinomanometric parameters (total score, TS), and by lung function tests. NPT was
      considered positive, when total nasal resistance (TNR) doubled in relation to
      basal value. RESULTS: H NPT was positive twice in 8/10 patients. Concordance
      between H concentration that induces a positive NPT measured by TNR or TS was
      observed. Regarding to specific NPT, 90 % of patients were positive to Dp and 60
      % to Bt. There was no concordance between the allergen concentration that induces
      a positive SPT and a positive NPT, considering the different concentrations.
      There were no modification in lung function tests during both specific and non
      specific provocation tests. CONCLUSIONS: NPT with H is an objective and
      reproducible method which allow evaluate nasal reactivity. Specific NPT have
      restricted indications, mainly when there where doubts about AR's etiology.

PMID- 11834185
TI  - Asthma and allergy in Turkish university students: Two cross-sectional surveys 5
      years apart.
AB  - BACKGROUND: prevalence of asthma and allergic diseases is increasing worldwide.
      We investigated the first-year university students to a) determine prevalence of
      asthma, and allergic diseases, b) compare prevalence with a similar study
      conducted in 1994, and c) investigate determinants of asthma, current wheeze and
      seasonal rhinitis. METHODS: an ECRHS based questionnaire was distributed to 5,406
      students and completed by 4,639 (response: 85.3 %) in september 1999. Information
      from the students residing in Turkey was used in the analyses (1,800 boys, 2,712
      girls). RESULTS: prevalence % of asthma (symptom and/or medicine), current wheeze
      and seasonal rhinitis were 2.1, 6.9 and 12.7 in boys, and 2.5, 7.2 and 14.5 in
      girls. Current smoking, pet ownership and family atopy was reported more
      frecuently in 1999 than 1994. Cough and seasonal rhinitis increased almost
      twofold. Asthma diagnosis and attack rate was similar in 1999 and 1994. Family
      atopy, pet in childhood, smoking and passive smoking in childhood increased the
      risk of asthma, and current wheeze. Family atopy, passive smoking and current pet
      ownership increased the risk of seasonal rhinitis. CONCLUSION: increased rate of
      smoking and pet ownership could contribute to the increased prevalence of asthma
      and allergic diseases in the last 5 years.

PMID- 11834183
TI  - Standardisation of glutaraldehyde-modified tyrosine-adsorbed tree pollen vaccines
      containing the Th1-inducing adjuvant, monophosphoryl lipid A (MPL).
AB  - BACKGROUND: a new range of allergy vaccines has been developed by the
      introduction of a relatively new Th1-inducing adjuvant known as 3-deacylated
      monophosphoryl lipid A (MPL). MPL adjuvant is of natural origin, derived from the
      lipopolysaccharide of Salmonella minnesota R595. This adjuvant is incorporated in
      a glutaraldehyde-modified pollen extract adsorbed to L-tyrosine (Pollinex
      Quattro). A major potential benefit provided by MPL adjuvant is the promotion of
      a Th1 response which enhances the efficacy of allergy vaccination and can
      consequently allow a reduction in the number of injections required for
      treatment. The standardisation of Pollinex Quattro tree pollen allergy vaccine is
      described and we include details of some innovative analytical procedures.
      METHODS AND RESULTS: an essential feature of the analytical strategy is the assay
      of the MPL adjuvant using a recently developed HPLC technique. The adjuvant has a
      complex chemical structure and the analysis is illustrated in detail. We give a
      full picture of the vaccine standardisation by describing biochemical and
      immunological characterisation of the allergen extract, together with some brief
      manufacturing details. CONCLUSIONS: a high overall level of standardisation is
      illustrated by a number of different tests applied to all stages of vaccine
      manufacture. Tree pollen allergen potency is measured following the pollen
      extraction, chemical modification and formulation as a tyrosine adsorbate. Good
      batch-to-batch reproducibility is shown. The HPLC assay for MPL adjuvant showed
      high quality resolution which did not vary when measuring raw material or when
      incorporated in the vaccine and the technically complex assay is shown to be
      reliable.

PMID- 11834186
TI  - Anaphylactic shock caused by impurities in orgotein preparations.
AB  - Previously reported allergic reactions to orgotein (superoxide dismutase)
      injections has assigned responsibility to this molecule, which is obtained from
      bovine liver. We report an anaphylactic shock probably caused by impurities
      contained in an orgotein preparation. Prick test to Peroxinorm (orgotein), BSA,
      and cow liver extract were positive but resulted negative with chymotrypsin,
      milk, meat and cow epithelium extracts. Tryptase levels determined 3, 24 hours
      and 15 days after the shock measured 6.32, 0.81 and 0.84 U/L respectively.
      Detection of specific IgE to Peroxinorm, BSA and chymotrypsin by ELISA was
      negative and positive to cow liver. Specific IgE to milk and cow epithelium by
      Pharmacia CAP system was negative. Immunoblotting with Peroxinorm revealed IgE
      specific bands at an apparent M.W of 67, 51, 56 and 16 kDa; immunoblotting with
      cow liver revealed bands at 72, 56, 50 and 36 kDa; immunoblotting with BSA and
      chymotypsin were negative. This case emphasises the role that 20 % of impurities
      of the pharmaceutical preparation may have in immediate hypersensitivity
      reactions.

PMID- 11834187
TI  - Erythema multiforme: As a complication of allergen-specific immunotherapy.
AB  - Here we present a 25-year-old female patient admitted with a complaint of
      blistering lesions on her face, neck, chest and extremities appearing after the
      first dosis of specific immunotherapy and diagnosed as erythema multiforme. To
      our knowledge, there are no papers in the literature reporting erythema
      multiforme due to specific immunotherapy.

PMID- 11834188
TI  - Dermatitis to captopril.
AB  - BACKGROUND: reports on delated cutaneous reactions to captopril have been seldom
      reported. Captopril is an angiotensin-converting enzyme (ACE) inhibitor and their
      cutaneous side-effects are documented, but little has been published concerning
      the usefulness of patch test when they occur. We presented the case of a patient
      who developed a cutaneous reaction induced by captopril with positive patch test.
      METHODS AND RESULTS: patch testing was performed with captopril, other ACE
      (enalapril, lisinopril ramipril), and European standard series. Following, we
      performed a double-blind oral challenge test with drugs who results was negative.
      Positive reaction were obtained to captopril at 4 days and the others test being
      negative. The same test were negative in five control patients. The patient
      tolerated enalapril, and lisinopril without problems. CONCLUSION: the
      allergological studies confirmed sensitisation to captopril and tolerance to
      lisinopril, and enalapril. When patch test are performed with several drugs of
      the same family, results seem to indicate an absence of cross-sensitivity, but in
      several patients, oral provocation test were needed because patch test gave no
      conclusive information.

PMID- 11834189
TI  - Serum histamine-releasing activity in a patient with idiopathic pulmonary
      haemosiderosis.
AB  - BACKGROUND: idiopathic pulmonary haemosiderosis (IPH) is a rare disorder
      characterized by intermittent, diffuse alveolar bleeding. The pathogenesis of the
      diseases is unclear, although an association with milk or gluten hypersensitivity
      has been described, and an immune-mediated damage of alveolar capillaries has
      been suggested. A previous report showed the release of histamine after cow's
      milk intake in a newborn with cow's milk intolerance and IPH. METHODS AND
      RESULTS: here, we report the detection of serum histamine-releasing activity
      (HRA) in a 30-year-old woman with IPH. The serum taken during an active phase of
      the disease induced histamine release from basophils of two normal donors;
      conversely, when the patient was receiving prednisone and azathioprine, and the
      disease was in remission, the serum HRA was reduced. Serum fractions with a MW
      lower than 100 kDa displayed an enhanced HRA; in contrast, serum fractions with
      MW above 100 kDa were not able to induce histamine release, suggesting that the
      activity was due to a cytokine and not to an immunoglobulin. CONCLUSIONS: the
      detection of serum HRA provides further evidence that the immune system is
      activated in the course of IPH and supports an immunologic basis for the alveolar
      capillary damage, which is responsible for alveolar bleeding.

PMID- 11834191
TI  - [Surgical treatment of Parkinson disease: turning the tide?].

PMID- 11834192
TI  - [Usefulness of olanzapine in the levodopa-induced psychosis in patients with
      Parkinson's disease].
AB  - BACKGROUND: To evaluate the antipsychotic efficacy of olanzapine (OLZ) in
      patients with Parkinson's disease (PD) and drug-induced psychosis (DIP) and its
      repercussion on the motor function. METHODS: Ten patients (5 women and 5 men)
      diagnosed of PD and DIP, aged 67 years (range: 50-81), with PD duration of 11.1
      years (range: 6-23), treated chronically with levodopa per day, received a dose
      of 2.5 or 5.0 mg OLZ daily. Data concerning improvement of psychosis and
      worsening of motor function was based on Positive And Negative Symptoms Scale
      (PANSS) and Unified Parkinsons Disease Rating Scale (UPDRS) motor. RESULTS:
      Psychotic symptoms were improved in all patients. In most of them the improvement
      was almost total. Seven patients increased levodopa dose on OLZ, but significant
      worsening of motor function was reported just in one patient. None of the
      patients had agranulocytosis in the blood monitoring. Two patients presented
      weight gain. Seven patients improved their cognitive status. CONCLUSIONS: We
      conclude that OLZ at the doses studied may have efficacy for DIP which appears in
      PD and does not induce worsening of motor function in most of the patients.

PMID- 11834193
TI  - [Language abnormalities in patients with multiple sclerosis].
AB  - BACKGROUND: Patients suffering from multiple sclerosis (MS) have a high frequency
      of cognitive deficits. Research has demonstrated impairments in memory,
      attention, information-processing speed, and executive functions. Although it has
      been traditionally held that language function is commonly preserved in MS, some
      studies have demonstrated language impairment in these patients, particularly in
      tasks of naming and word-generation. OBJECTIVES: The aim of the study was to
      examine language functioning in MS, with particular interest in naming ability
      and verbal fluency. MATERIAL AND METHODS: Thirty patients with MS, and 30
      neurologically intact normal controls, matched for age and educational level were
      evaluated. As part of a wider neuropsychological evaluation, all subjects were
      administered the Boston Naming Tests. To compare performances, a comprehensive
      classification of error types was devised. RESULTS: MS patients showed
      significantly lower performance on both linguistic measures than the control
      subjects. On the Boston Naming Test, MS patients obtained significant lower
      scores than controls, with a high rate of semantic errors. Additionally, they
      tended to show an also high number of visuoperceptual errors. Low scores on
      naming task correlated with low performance on verbal fluency. CONCLUSIONS: This
      study reveals that language function can be impaired in MS, and that naming
      difficulties are a frequent finding. This naming deficit seems to have a double
      origin, stemming from disruption at the levels of the perceptual and/or the
      semantic systems.

PMID- 11834194
TI  - [Proposal of criteria for clinical diagnosis of mild cognitive impairment,
      dementia and Alzheimer's disease].
AB  - The most widely accepted criteria for Alzheimer's disease (AD) diagnosis (NINCDS
      ADRDA and DSM-IV) do not allow to differentiate accurately between AD and other
      degenerative dementias which have recently formulated criteria for its clinical
      diagnosis. Therefore, it is necessary to bring AD diagnostic criteria up to date
      in order to optimise their specificity, by assessing its most specific clinical
      manifestations, its most representative markers and those features typical of
      other diseases which are usually taken into account for a differential diagnosis.
      According to the latest reports on the subject, the disturbances suffered by
      memory, behaviour and the rest of cognitive and executive functions must be
      equally considered when establishing the syndromic diagnosis of dementia; this
      will always require the coexistence of an evident functional impairment. Due to
      this, the concepts of "dementia" and "mild cognitive impairment" should be
      clearly distinguished. For the time being, AD can only be diagnosed when dementia
      has been proved and this shows a series of cognitive, behavioural and
      neurological features which are representative of it. Nevertheless, some
      diagnostic markers appear to be precocious and specific enough to try to identify
      those patients who suffer from mild cognitive impairment due to an incipient
      stage of AD. We are suggesting some criteria for the clinical diagnosis of
      dementia, mild cognitive impairment and AD that seem to be more detail

PMID- 11834195
TI  - [Lluis Barraquer Roviralta (1855-1928), founder of Spanish clinical neurology.
      The origin of the first school of neurology in Spain].
AB  - Lluis Barraquer Roviralta (1855-1928) was the founder, when he was 27 years old,
      of the first nucleus of clinical Neurology and electro therapy in Spain, in 1882.
      This nucleus was located in the Hospital de la Sta. Creu i Sant Pau (of the Holy
      Cross and Sant Paul), dated from 1401. His work was marked and founded upon a
      great and deep knowledge of the anatomy of the central and peripheral nervous
      system, and of the fine semiology approach of its pathological derangement, and
      also of the electrodiagnostic techniques. In this way he could make several
      princeps descriptions: of the generalisated muscular dystonia (1897), of the
      cephalothoraric lypodystrophy (1906), of the grasp reflex of the foot (1921) and
      of the diffused hemilateral atrophy of dystrophic-sympathetic pathogenesis
      (1925). He makes also a very minocious analysis of the idiomuscular reaction. He
      promoted the firts steps of neurosurgery in Barcelona. Another aspect of its
      activity was the study of the degeneration and regeneration of the peripheral
      nervous system in rabbits. He described the neural semiology of the lepra. He
      performed personaly a great activity in collecting images of the semiology of
      nervous disease and of macroscopic pathological anatomy, leaving about 2,000
      images.

PMID- 11834196
TI  - [Hereditary ataxias and paraplegias: a clinicogenetic review].
AB  - Hereditary ataxias encompass a series of syndromes basically characterised by
      progressive cerebellar ataxia of slow clinical course (occasionally, periodic
      ataxia or spastic paraparesis) and primary spinocerebellar degeneration. The
      prevalence ratio of these syndromes in Spain is 20 cases per 100,000 inhabitants.
      Initially the ataxias were classified on the basis of clinicopathological
      criteria. Starting from the seminal papers by Harding published 20 years ago, a
      clinicogenetic classification was introduced that has given way to the present
      molecular classification. There have been localised about forty loci. In dominant
      ataxias the most frequent molecular defect is a dynamic CAG expansion responsible
      for abnormal polyglutamine tract transcription. The identification of such
      molecular defect has made it possible detection of gene carriers in clinical
      practice, this involving both presymptomatic and prenatal diagnosis; moreover,
      such molecular discoveries have contributed to develop a new pathogenetic era. A
      homozygous and intronic GAA expansion is the molecular basis of Friedreich's
      ataxia. This finding has also made it possible a molecular diagnosis in clinical
      practice. Molecular studies have demonstrated that hereditary spastic paraplegia
      is another heterogeneous genetic disorder.

PMID- 11834197
TI  - [Bilateral temporal leukoencephathy in neurosyphilis].

PMID- 11834198
TI  - [Usefulness of functional magnetic resonance imaging and spectroscopy in the
      diagnosis of frontotemporal dementia].
AB  - Early diagnosis of frontotemporal dementia is difficult, especially at its early
      stages, being mainly misdiagnosed as a psychiatric condition. The main source of
      uncertainty comes from the primacy of behavioral disturbances, for which
      sufficiently validated detection tools are not available. The increasing
      development of magnetic resonance (MR) techniques permits a triple approach that
      combines morphology, biochemistry and perfusion in the study of dementing
      neurodegenerative conditions. A 64-year-old male patient is described with
      prominent behavioral disturbances and a frontotemporal pattern of cognitive
      impairment. He met criteria for frontotemporal dementia. Conventional MR imaging
      showed minimal frontotemporal atrophy. A moderate hypoperfusion of the frontal
      lobes was observed in the MR perfusion study. The spectroscopy showed a decrease
      of the n-acetyl-aspartate peak in the medial frontal region with normal values in
      the medial parietal region. The whole MR imaging study aided to distinguish
      frontotemporal dementia from other conditions, such as brain structural processes
      and depression, offering relevant information for prognostic and therapeutic
      purposes. The usefulness of the new MR imaging techniques in the early diagnosis
      of dementing neurodegenerative conditions must be confirmed by larger studies
      accompanied by pathological material.

PMID- 11834199
TI  - [Antithrombotic treatment of fusiform aneurysms of the basilar artery].
AB  - Fusiform aneurysms are unusual, and they are most found in the vertebrobasilar
      system. Although the presence of such aneurysms has been related to atheromatous
      degeneration of the arterial wall, in many cases the cause of their formation is
      unknown. The clinical manifestations of fusiform aneurysms of the vertebrobasilar
      system are generally due to mass effect with compression of adjacent structures
      or to ischemic events; exceptionally they are due to subarachnoidal haemorrhage.
      We present the case of a patient with symptoms suggestive of brainstem ischemic
      damage, in which neuroimaging showed a fusiform aneurysm of the basilar artery
      with an intraaneurysmatic thrombus. Antiaggregation did not prevent new ischemic
      events, so anticoagulation therapy was initiated. The patient remained
      asymptomatic at 8 months of follow-up. The treatment of fusiform aneurysms is
      controversial; however, there are some evidences in the literature supporting
      that patients with ischemic events may be treated with long term anticoagulation,
      especially in cases of non-giant aneurysms of the vertebrobasilar system not
      accompanied by aneurysms in other sites.

PMID- 11834200
TI  - [Raeder's paratrigeminal syndrome as manifestation of the Chiari malformation].

PMID- 11834202
TI  - Sexual dimorphism in age-related changes in UCP2 and leptin gene expression in
      subcutaneous adipose tissue in humans.
AB  - The influence of age and gender on uncoupling protein 2 (UCP2) expression and its
      relationship with leptin expression in subcutaneous adipose tissue has been
      studied in humans. Samples of subcutaneous adipose tissue were obtained from 41
      adult subjects (20 women and 21 men), with an age range of 28 to 84 years, and
      body mass index (BMI) of 19 to 36 Kgm(minus sign2). UCP2 and leptin mRNA
      expression was determined by northern blot. In women, both leptin and UCP2
      expression in the subcutaneous adipose tissue increased significantly with age (r
      = 0.490 p < 0.05 and r = 0.475 p < 0.05, respectively). In men, in contrast, a
      negative correlation was found between leptin expression and age (r = minus
      sign0.678 p < 0.001), while no significant correlation was apparent between UCP2
      expression and age (r = minus sign0.077). In addition, there was a positive
      correlation between UCP2 and leptin expression in women (r = 0.656 p < 0.01).
      These data show important gender dependent differences in the age-related changes
      in leptin and UCP2 expression in subcutaneous adipose tissue in humans.

PMID- 11834201
TI  - [Does ambulatory neurology care have the quality necessary for progress in
      neurology?].

PMID- 11834203
TI  - Non-essential amino acids play an important role in adaptation of the rat
      exocrine pancreas to high nitrogen feeding.
AB  - We have previously demonstrated that feeding a diet with a high amino acid (60%
      AA diet) content, as a mixture simulating casein, induced pancreatic growth and
      pancreatic protease production in rats. In the present study, we examined the
      effects of an increasing dietary content of essential amino acids (EAA, x1 - x3
      in exp. 1 and x1 - x3.3 in exp. 2) and non-essential amino acids (NEAA, x1 - x3
      in exp. 1 and x1 - x5.2 in exp. 2) on pancreatic growth, amylase and protease
      adaptation using casein-type amino acid mixtures (exp. 1, basal diet; 20% AA
      diet) and egg white-type amino acid mixtures (exp. 2, basal diet; 12% AA diet).
      Pancreatic growth and trypsin activity were induced as the dietary content of
      NEAA was increased in experiments 1 and 2. Amylase activity in the pancreas was
      also induced as the dietary content of NEAA was increased, even with the decrease
      in dietary carbohydrate in experiment 2. The values of all pancreatic variables
      decreased with the increase in dietary EAA (x2 and x3) without an increase in
      NEAA. The changes in the pancreas were coincident with increases in plasma
      arginine and lysine concentrations and a decrease in the plasma alanine
      concentration. In rats fed a 60% AA diet (EAA and NEAA x3), in the case of which
      the EAA content was balanced with the NEAA content, pancreatic growth and
      protease production increased and reached maximum levels as the plasma amino acid
      concentrations decreased, except for alanine. These results show that NEAA, not
      EAA, are associated with induction of pancreatic growth and protease production
      upon feeding a diet with a high AA content, and that some metabolites may be
      involved in the induction process. The suppression of pancreatic growth and
      protease production in rats fed the high EAA diets without balanced NEAA may be
      associated with impairment of amino acid metabolism rather than the increments in
      the concentration of one or more essential amino acids. Our results also suggest
      that there is an unknown mechanism or unknown factors involved in regulating
      pancreatic amylase.

PMID- 11834204
TI  - Diet and diabetic state modify glycogen synthase activity and expression in rat
      hepatocytes.
AB  - Glycogen synthase (GS), a key regulatory enzyme in glycogen synthesis, is
      controlled by multisite phosphorylation and allosteric regulation and is
      activated by insulin. This study investigated changes in GS activity and
      expression in hepatocytes isolated from rats under altered nutritional and
      diabetic conditions. Experiments were carried out in healthy rats fed a chow
      diet, rats on high simple sugar (60% of energy from fructose and sucrose) or high
      fat (46% of energy from fat) diet, and in rats with streptozotocin induced
      diabetes. In the presence of insulin, activated GS activity (GS(I) form) was
      increased by 89% in hepatocytes isolated from healthy rats. The stimulatory
      effect of insulin on GS activity and expression was blunted by cycloheximide and
      actinomycin treatment. In rats fed a high simple sugar or high fat diet, insulin
      stimulation of GS(I) in isolated hepatocytes was impaired and GS expression was
      significantly lower in rats fed the high fat diet in comparison to controls. GLUT
      2 protein expression was significantly lowered by both the high fat and high
      simple sugar diets. In hepatocytes isolated from diabetic rats, total GS activity
      (GS(T)) was lower than in hepatocytes from healthy animals. Insulin added to the
      incubation medium did not stimulate GS activity, demonstrating impaired
      sensitivity to insulin in diabetic rats. However, insulin administration
      significantly increased GS expression indicating that a defect in synthase
      phosphorylation may be responsible for impaired GS activity in the diabetic
      state. The results presented in this study further confirm that GS activity is
      affected by both dietary and hormonal factors which can be measured in a rat
      hepatocyte model.

PMID- 11834205
TI  - Proliferation of peripheral blood mononuclear cells causes increased expression
      of the sodium-dependent multivitamin transporter gene and increased uptake of
      pantothenic acidopen star
AB  - Antigenic or mitogenic stimulation of peripheral blood mononuclear cells (PBMC)
      causes rapid cell proliferation. PBMC proliferation is associated with increased
      activities of pantothenic acid-dependent metabolic pathways, suggesting increased
      demand for pantothenic acid. We sought to determine whether PBMC respond to
      proliferation by increased cellular uptake of pantothenic acid and, if so, by
      what mechanism(s) the increased uptake is mediated. Uptake of pantothenic acid
      into PBMC was mediated by the sodium-dependent multivitamin transporter, SMVT, as
      judged by sodium dependency of uptake, substrate affinity and specificity, and RT
      PCR of PBMC RNA. Proliferating PBMC accumulated two times more [3H]pantothenic
      acid than quiescent PBMC. Rates of [3H]pantothenic acid uptake paralleled rates
      of PBMC proliferation, as judged by uptake of [3H]thymidine. The increased uptake
      of [3H]pantothenic acid into proliferating PBMC was mediated by increased
      expression of SMVT (as judged by RT-PCR using total RNA from PBMC), leading to an
      increased number of transporters on the cell surface (as judged by maximal
      transport rates for pantothenic acid). We conclude that proliferating PBMC
      increase expression of the gene encoding SMVT to increase uptake of pantothenic
      acid.

PMID- 11834206
TI  - Effect of dietary oils enriched with n-3 fatty acids on survival of mice.
AB  - Female mice were fed a conventional diet, shifted at 119 days of age to a diet
      supplemented with 10 wt % lard (Lar), high-linoleic (n-6) safflower oil (Saf),
      rapeseed oil (low-erucic, Rap), high-alpha-linolenic (n-3) perilla oil (Per) or a
      mixture (1:9) of ethyl docosahexaenoate (n-3) and soybean oil (DHA/Soy). Weight
      gain was less in the Per group than in the other groups at 497 days of age. In
      the Rap group, proteinuria was more severe than in the Saf, Per and DHA/Soy
      group, and hepatic triacylglycerol accumulation was greater than in the other
      groups. The mean survival time of the DHA/Soy group (753 days) was significantly
      longer than in the Lar group (672 days) and Saf group (689 days); the differences
      among other groups (e.g., 701 days in the Per group and 712 days in the Rap
      group) were not statistically significant. Although DHA is more susceptible to
      auto-oxidation than other major fatty acids in the air, an oil containing DHA was
      found to increase the survival of mice. Rapeseed oil that decreases the survival
      time of SHRSP rats was found to be safe in the mouse strain used in this study
      when survival was an end point.

PMID- 11834207
TI  - Phospholipid hydroperoxide glutathione peroxidase activity and vitamin E level in
      the liver microsomal membrane: effects of age and dietary alpha-linolenic acid
      deficiency.
AB  - Age and diet-induced variations of phospholipid hydroperoxide glutathione
      peroxidase (PHGPx) activity and alpha-tocopherol concentration in the liver
      microsomal membrane were studied in male Wistar rats fed a semipurified diet
      either balanced in n-6 and n-3 polyunsaturated fatty acids (PUFA) (Control) or
      deprived of alpha-linolenic acid, i.e. n-3 PUFA (Deficient) over two generations.
      The animals were studied at the age of 6 months (adult) or 24 months (old). Both
      PHGPx activity and vitamin E level were significantly higher in 24-month old rats
      as compared to 6-month old rats. By contrast, the thiobarbituric acid reactive
      substances (TBARS) following stimulated in vitro peroxidation of membrane lipids
      were markedly lower (P < 0.01) with aging. The fatty acid composition of
      microsomal membrane phospholipids (PL) was also considerably modified by age. In
      particular, the levels of arachidonic acid and total n-6 PUFA were lower (P <
      0.001) whereas n-3 PUFA levels were higher (P < 0.001) in most PL main classes.
      The alpha-linolenic acid deficiency markedly influenced these age-related
      changes. The higher PHGPx activity in the old rats as compared to the adult rats
      was only significant in those fed the control diet. In the 6-month old rats (but
      not in the 24-month old rats), the deficient diet led to a higher membrane
      vitamin E level and to lower TBARS production than the control diet. The results
      suggest that the nature of dietary PUFA may influence the age-related variations
      in this pair of membrane antioxidants and also in the fatty acid composition of
      microsomes.

PMID- 11834208
TI  - The effect of a Tropaeolum speciosum oil supplement on the nervonic acid content
      of sphingomyelin in rat tissues.
AB  - The lipids of Tropaeolum speciosum (T. speciosum) are a rich source of naturally
      occurring nervonic acid (24:1n-9). We report that adding a T. speciosum oil
      supplement to a semi-purified diet significantly increased the amount of 24:1n-9
      in liver and heart, but not brain, sphingomyelin (SM) of young rats. The
      bioavailability of 24:1n-9 from the lipids of T. speciosum was similar to that of
      24:1n-9 ethyl ester in this rat bioassay.

PMID- 11834209
TI  - Protective effect of vitamin E in dimethoate and malathion induced oxidative
      stress in rat erythrocytes.
AB  - Organophosphate (OP) pesticides such as dimethoate and malathion intoxication has
      been shown to produce oxidative stress due to the generation of free radicals and
      alter the antioxidant defense system in erythrocytes. It is possible that vitamin
      E being present at the cell membrane site may prevent OP-induced oxidative
      damage. In the present study, rats were pretreated orally with vitamin E (250
      mg/kg body wt, twice a week for 6 weeks) prior to oral administration of a single
      low dose of dimethoate and/or malathion (0.01% LD(50)). The result showed that
      treatment with OP increased lipid peroxidation (LPO) in erythrocytes, however,
      vitamin E pretreated rats administered OP's showed decreased LPO in erythrocytes.
      The increase in the activities of superoxide dismutase (SOD) and catalase (CAT)
      and total-SH content in erythrocytes from dimethoate and/or malathion treated
      rats as compared to control appears to be a response towards increased oxidative
      stress. Vitamin E pretreated animals administered OP's showed a lowering in these
      parameters as compared to OP treated rats which indicates that vitamin E provide
      protection against OP-induced oxidative stress. The glutathione-S-transferase
      (GST) activity in erythrocytes was inhibited in OP intoxicated rats which
      partially recovered in vitamin E pretreated animals administered OP's. Inhibition
      in erythrocyte and serum acetylcholinesterase (AChE) activity was not relieved in
      vitamin E pretreated rats administered OP's probably due to the competitive
      nature of enzyme inhibition by OP's. The results show that vitamin E may
      amelierate OP-induced oxidative stress by decreasing LPO and altering antioxidant
      defense system in erthrocytes.

PMID- 11834210
TI  - Antioxidant effect of red wine anthocyanins in normal and catalase-inactive human
      erythrocytes.
AB  - Previous studies reported that aged red wine, but not novel red wine or white
      wine protects human red blood cells from oxidative damage induced in vitro by
      H(2)O(2.) Here, we demonstrate that the beneficial properties of aged red wine
      are due, at least in part, to the presence of anthocyanins. We firstly measured
      the "antioxidant power" of an Italian red wine (Taurasi, Avellino) and that of
      its anthocyanin fractions by using Ferric Reducing Antioxidant Power Assay.
      Subsequently, we demonstrate that fractions containing anthocyanins lower ROS
      (reactive oxygen species) and methemoglobin production in human erythrocytes
      treated with H(2)O(2.) Finally, we reported that the protective effects of
      anthocyanins were also confirmed in an experimental model in which RBCs were
      deprived of catalase activity by treatment with 4 mM sodium azide. The results
      obtained clearly demonstrate that red wine anthocyanins protect human RBCs from
      oxidative stress.

PMID- 11834211
TI  - Nutritional value of the marine invertebrates Anemonia viridis and Haliothis
      tuberculata and effects on serum cholesterol concentration in ratsopen star
AB  - The purpose of this study was to determine the nutritional value of diets with
      protein from two marine species (Haliotis tuberculata and Anemonia viridis) as
      compared to a high-quality protein reference based on casein or casein
      supplemented with olive oil. We also investigated the effects of these diets on
      serum lipid levels. Male rats were fed these diets for 23 days. Protein quality
      indicators (true digestibility, net protein utilization, biological value) were
      similar to those obtained for casein-based feeds except for lower true
      digestibility and net protein utilization values for the Anemonia viridis feed.
      HDL-cholesterol level was significantly higher (p < 0.05) in the groups fed
      marine species or casein supplemented with olive oil than in the casein group.
      Total-cholesterol level was higher in the group fed Haliotis tuberculata fed than
      in the other groups. These results suggest that these marine species are a good
      protein source, and that they may have positive effects on serum cholesterol
      level.

PMID- 11834212
TI  - Cytosolic enzymes from rat tissues that activate the cooked meat mutagen
      metabolite N-Hydroxyamino-1-methyl-6- phenylimidazo[4,5-b]pyridine (N-OH-PhIP).
AB  - Heterocyclic amines are formed during the cooking of foods rich in protein and
      can be metabolically converted into cytotoxic and mutagenic compounds. These
      "cooked-food mutagens" constitute a potential health hazard because DNA damage
      arising from dietary exposure to heterocyclic amines can modify cell genomes and
      thereby affect future organ function. To determine enzymes responsible for
      heterocyclic amine processing in mammalian tissues, we performed studies to
      measure genotoxic activation of the N-hydroxy form of 2-amino-1-methyl-6
      phenylimidazo[4,5-b]pyridine (PhIP) --a common dietary mutagen. O
      Acetyltransferase, sulfotransferase, kinase, and amino-acyl synthetase activities
      were assayed using substrate-specific reactions and cytosolic enzymes from
      newborn and adult rat heart, liver, spleen, kidney, brain, lung, and skeletal
      muscle. The resultant enzyme-specific DNA adduct formation was quantified via
      (32)P-postlabeling techniques. In biochemical assays with rat tissue cytosolic
      proteins, O-acetyltransferases were the enzymes most responsible for N-hydroxy
      PhIP (N-OH-PhIP) activation. Compared to O-acetyltransferase activation, there
      was significantly less kinase activity and even lesser amounts of
      sulfotransferase activity. Proyl-tRNA synthetase activation of N-OH-PhIP was not
      detected. Comparing newborn rat tissues, the highest level of O-acetyltransferase
      mutagen activation was observed for neonatal heart tissue with activities ranked
      in the order of heart > kidney > lung > liver > skeletal muscle > brain > spleen.
      Enzymes from cultured neonatal myocytes displayed high O-acetyltransferase
      activities, similar to that observed for whole newborn heart. This tissue
      specificity suggests that neonatal cardiac myocytes might be at greater risk for
      damage from dietary heterocyclic amine mutagens than some other cell types.
      However, cytosolic enzymes from adult rat tissues exhibited a different O
      acetyltransferase activation profile, such that liver > muscle > spleen > kidney
      > lung > brain > heart. These results demonstrated that enzymes involved in
      catalyzing PhIP-DNA adduct formation varied substantially in activity between
      tissues and in some tissues, changed significantly during development and aging.
      The results further suggest that O-acetyltransferases are the primary activators
      of N-OH-PhIP in rat tissues.

PMID- 11834213
TI  - Effects of dietary fats on red blood cell membrane insulin receptor in normo- and
      hypercholesterolemic miniature swine.
AB  - It has been demonstrated that the type of dietary fat affects insulin receptors
      in various tissues in normal humans and animals by altering membrane fluidity.
      This study compares the effects of n-3 fatty acids from fish oil and n-6 fatty
      acids from corn oil on red blood cell membrane insulin receptors in normal and
      hypercholesterolemic minipigs. A group of minipigs were made hypercholesterolemic
      by feeding cholesterol and lard for 2 months; the other group served as controls
      and was fed stock diet. Both groups were then fed experimental diets containing
      either corn oil or menhaden oil or a mixture of the two for 23 additional weeks.
      Blood was collected at 0, 2, 12 and 23 weeks after the start of the experimental
      diets and membranes were prepared from the red blood cells. Insulin binding to
      red blood cell membranes was measured by radioreceptor assay. Plasma insulin was
      measured by radioimmunoassay. Insulin binding to red blood cell membrane was
      compared with the fluidity of the membrane measured and reported earlier. There
      was no significant effect of cholesterol feeding on plasma insulin
      concentrations. After 23 weeks on experimental diet plasma insulin was
      significantly higher in minipigs fed menhaden oil compared to those fed corn oil.
      No such effect was observed in hypercholesterolemic minipigs. No significant
      effect of either hypercholesterolemia or fish oil was observed on red blood cell
      insulin binding. A significant negative relationship was observed between insulin
      binding and anisotropy at 4 degrees C for all probes but at 37 degrees C
      significant negative relationship was observed only with polar probes. The data
      suggest that n-3 fatty acids from fish oil significantly increases plasma insulin
      in minipigs compared to n-6 fatty acids from corn oil. However, the unsaturation
      has no significant effect on insulin receptors on erythrocytes. Similarly, prior
      hypercholesterolemic state also has no effect on plasma insulin levels or the
      insulin binding to red blood cell membranes.

PMID- 11834214
TI  - Dietary polyunsaturated n-6 lipids effects on the growth and fatty acid
      composition of rat mammary tumors.
AB  - The aim of this study was to analyze the effects of a polyunsaturated n-6 high
      fat diet on rat DMBA-induced breast cancer at different stages of the
      carcinogenesis and to investigate if changes in the tumor fatty acid composition
      are one of the mechanisms by which dietary lipids could exert their effects. 14
      fatty acids were evaluated in 6 lipid fractions. The results firstly showed that
      this high-fat diet stimulated the malignant mammary tumor growth, mainly all in
      the promotion group. The tumor lipid analysis indicated: 1) that each lipid
      fraction presented distinct major fatty acids (>5%) which were not the most
      abundant in the diet, except in the case of the triacylglicerides, suggesting the
      different resistance to dietary fatty acid modification of the tumor lipid
      fractions; 2) a higher arachidonic acid content in the fractions with less
      linoleic acid, above all in phospholipids, particularly in the
      phosphatidylethanolamine, indicating a different efficiency of conversion; 3) the
      three most abundant fatty acids in the dietary lipid (18:2n-6, 18:1n-9 and 16:0)
      were those which essentially displayed the differences between groups; thus, the
      high-fat diet changed the tumor lipid profile, increasing the 18:2n-6 relative
      content and decreasing that of the 18:1n-9; differences were significant in
      phosphatidylcholine, free fatty acids and triacylglycerides. Any change was
      obtained in the phosphatidylinositol. The greatest number of differences was
      found in the promotion group. Taken as a whole, our results suggest the different
      roles of lipid fractions in breast cancer cells and an association between cancer
      malignancy and the content of linoleic and oleic acids.

PMID- 11834215
TI  - Does lack of tocopherols and tocotrienols put women at increased risk of breast
      cancer?
AB  - Breast cancer is the leading site of new cancers in women and the second leading
      cause (after lung cancer) of cancer mortality in women. Observational studies
      that have collected data for dietary exposure to alpha-tocopherol with or without
      the other related tocopherols and tocotrienols have suggested that vitamin E from
      dietary sources may provide women with modest protection from breast cancer.
      However, there is no evidence that vitamin E supplements confer any protection
      whatever against breast cancer. Observational studies that have assessed exposure
      to vitamin E by plasma or adipose tissue concentrations of alpha-tocopherol have
      failed to provide consistent support for the idea that alpha-tocopherol provides
      any protection against breast cancer. In addition, evidence from studies in
      experimental animals suggest that alpha-tocopherol supplementation alone has
      little effect on mammary tumors. In contrast, studies in breast cancer cells
      indicate that alpha- gamma-, and delta-tocotrienol, and to a lesser extent delta
      tocopherol, have potent antiproliferative and proapoptotic effects that would be
      expected to reduce risk of breast cancer. Many vegetable sources of alpha
      tocopherol also contain other tocopherols or tocotrienols. Thus, it seems
      plausible that the modest protection from breast cancer associated with dietary
      vitamin E may be due to the effects of the other tocopherols and the tocotrienols
      in the diet. Additional studies will be required to determine whether this may be
      the case, and to identify the most active tocopherol/tocotrienol.

PMID- 11834216
TI  - Effect of sodium molybdate on carbohydrate metabolizing enzymes in alloxan
      induced diabetic rats.
AB  - We evaluated the effect of sodium molybdate on carbohydrate metabolizing enzymes
      and mitochondrial enzymes in diabetic rats. Diabetic rats showed a significant
      reduction in the activities of glucose metabolising enzymes like hexokinase,
      glucose-6-phosphate dehydrogenase, glycogen synthase and in the level of
      glycogen. An elevation in the activities of aldolase, glucose-6-phosphatase,
      fructose 1,6- bisphosphatase, glycogen phosphorylase and in the level of blood
      glucose were also observed in diabetic rats when compared to control rats. The
      activities of mitochondrial enzymes isocitrate dehydrogenase, alpha-ketoglutarate
      dehydrogenase, succinate dehydrogenase, malate dehydrogenase, NADH-dehydrogenase
      and cytochrome-C-oxidase were also significantly lowered in diabetic rats.
      Molybdate administration to diabetic rats reversed the above changes in a
      significant manner. From our observations, we conclude that administration of
      sodium molybdate regulated the blood sugar levels in alloxan-induced diabetic
      rats. Sodium molybdate therapy not only maintained the blood glucose homeostasis
      but also altered the activities of carbohydrate metabolising enzymes. Molybdate
      therapy also considerably improved the activities of mitochondrial enzymes,
      thereby suggesting its role in mitochondrial energy production.

PMID- 11834217
TI  - N-3 and n-6 fatty acids stimulate restitution by independent mechanisms in the
      IEC-6 model of intestinal wound healing.
AB  - We have shown that intestinal epithelial restitution is stimulated by n-3 and n-6
      fatty acids. The current studies were undertaken to elucidate the mechanistic
      pathway(s) involved in this fatty acid modulation of restitution. Inhibition of
      phospholipase A(2) and eicosanoid synthesis and its effect on fatty acid
      stimulation of cellular migration in confluent, wounded IEC-6 monolayers was
      examined. The production of prostaglandin E(2) and transforming growth factor
      beta(1) were also measured in fatty acid supplemented cultures. Inhibition of
      phospholipase A(2) attenuated the effect of fatty acid stimulation of restitution
      in both n-3 and n-6 supplemented cultures. The lipoxygenase inhibitor,
      nordihydorguaretic acid (2 &mgr;mol/L), had no effect on stimulation of migration
      by fatty acids. The cyclooxygenase inhibitor piroxicam (5 &mgr;mol/L) and
      cyclooxygenase-2 specific inhibitors dexamethasone (2 &mgr;mol/L) and NS-398 (10
      &mgr;mol/L) all attenuated the fatty acid stimulation of migration by n-6 fatty
      acids but had no effect on n-3 stimulated restitution. Prostaglandin E(2)
      production in n-6 supplemented cultures was significantly greater than in control
      and n-3 supplemented cultures and was partially inhibited by dexamethasone and NS
      398. Latent transforming growth factor beta(1) production in n-3 supplemented
      cultures was significantly higher than baseline and n-6 supplemented cultures.
      Docosapentaenoic acid supplementation significantly enhanced the restitution
      process and NS-398 treatment had no effect on this stimulation of cellular
      migration. The liberation of fatty acid from the sn-2 position of phospholipid
      appears to be necessary for both n-3 and n-6 fatty acid stimulation of
      restitution. N-6 fatty acid modulation of restitution appears to be mediated
      through the production of eicosanoid products, however, prostaglandin E(2) does
      not appear to be the sole prostanoid involved. N-3 supplementation elevates the
      production of latent transforming growth factor beta(1) and may be responsible
      for n-3 mediated stimulation of restitution. These results further emphasize that
      n-3 and n-6 fatty acids convey their effects through unique pathways.

PMID- 11834218
TI  - Reversibility of the changes induced by n-3 fatty acids in mouse plasma, liver
      and blood cell lipids.
AB  - The changes induced by dietary n-3 fatty acids (FA) in the lipids and FA of
      plasma, liver and blood cells, and their reversibility, was studied in mice given
      a diet containing 9% fish oil (FO) for 2 weeks and then returned to, and kept for
      another 2 weeks on, the usual standard lab chow diet. In plasma, the
      concentrations of phospholipids (PL), mostly phosphatidylcholine (PC),
      triacylglycerols (TG), cholesterol and cholesterol esters (CE) decreased rapidly
      after starting the FO diet, and remained low from day 3 onwards. This decrease
      was concomitant with a remarkable reduction in the n-6 FA, especially 18:2n-6,
      not compensated for by the relative enrichment in n-3 FA induced by FO. In liver,
      TG and CE decreased and PL slightly increased, all of them showing reduced n-6/n
      3 ratios. Sphingomyelin, which lacks polyunsaturated FA other than small amounts
      of 18:2 and 24:2n-6, showed altered ratios between its very long chain monoenes
      and saturates. In the washout phase, the most rapid event was an immediate
      increase in 18:2n-6 and after a few days in 20:4n-6 in plasma and liver, where
      most of the lipid and FA changes were reversed completely in about 10 days. In
      the case of blood cells even 2 weeks were insufficient for a reversal to the
      initial n-6/n-3 ratios. The lipid class responsible for this lack of
      reversibility was phosphatidylethanolamine, PC having returned to the initial
      fatty acid composition during the stated period.

PMID- 11834219
TI  - Effect of different durations of exercise on transferrin-bound iron uptake by rat
      erythroblast.
AB  - This study evaluated effects of different durations of exercise on transferrin
      receptor (TfR) expression on the membrane of rat erythroblasts. Female rats were
      assigned to six groups: 3, 6 and 12 months of strenuous exercise (swimming 2
      h/day, 5 days/wk) groups and their corresponding controls. At the end of
      experiments, the erythroblasts were isolated for Tf binding assay and transferrin
      bound iron (Tf-Fe) uptake. Tissue non-heme iron and hematological iron indices
      were also measured. The TfR number on the cells was about 603,189 plus minus
      107,562, 890,150 plus minus 164,849 and 384,695 plus minus 46,295 molecules/cell
      in three control groups (3, 6, 12 months) respectively. Exercise groups had
      significantly higher levels of TfR than those of the control groups, being
      1,374,137 plus minus 243,677, 2,175,360 plus minus 462,737 and 1,012,759 plus
      minus 249,423 molecules/cell in 3, 6 and 12 months of exercise groups
      respectively (p < 0.05). After 30 min of incubation, cellular Tf approached to
      levels of 8.28 plus minus 1.94, 10.73 plus minus 3.30 and 6.60 plus minus 0.93
      fmole/10(6) cells in 3, 6 and 12 months of exercise groups, while the
      corresponding control values were 3.09 plus minus 0.36, 5.03 plus minus 1.01 and
      2.51 plus minus 0.88 fmole/10(6) cells respectively (all P < 0.05). The rates of
      cellular iron accumulation were 7.07 (3), 8.79 (6) and 5.96 (12 month)
      fmole/10(6) cells/min in the exercised rats and 2.91, 3.85, and 2.03 fmole/10(6)
      cells/min in their corresponding controls (all p < 0.05). However, no significant
      difference was observed in the ratios (Exercise/Corresponding control) of the
      increased TfR expression, Tf-Fe uptake and Tf endocytosis as well as of the
      decreased plasma iron and tissue non-heme iron levels induced by different
      periods of exercise. Furthermore, the increase in the length of exercise (6 or 12
      month) did not induce a remarkable decrease in plasma hemoglobin and hematocrit.
      These results indicate that a true iron deficiency or 'sport anemia' can not
      develop even if under longer periods (6 or 12 month) of strenuous exercise.

PMID- 11834220
TI  - Polyunsaturated fatty acids downregulate the low density lipoprotein receptor of
      human HepG2 cells.
AB  - The aim of the study was to investigate the effect of different fatty acids on
      the low density lipoprotein (LDL) receptor of cultured human liver HepG2 cells.
      Previous studies investigating the effect of fatty acids on LDL expression have
      reported conflicting findings and are limited to measurements of LDL receptor
      binding activity. Therefore, this study is unique in that the relative effects of
      different fatty acids on the LDL receptor were investigated at three different
      stages of expression: 1) functional cellular LDL binding activity, 2) amount of
      LDL receptor protein and 3) LDL receptor mRNA level. The HepG2 cells were
      incubated for 24 hr with either 100 &mgr;M palmitic, oleic, linoleic or
      eicosapentaenoic acid (EPA). The measurement of LDL receptor binding activity was
      with colloidal gold-LDL conjugates, cellular LDL receptor protein was by western
      blotting and LDL receptor mRNA by Southern blotting of reverse-transcribed,
      polymerase chain reaction-amplified cDNA. The LDL receptor binding activity,
      protein and mRNA levels decreased as the degree of unsaturation of the fatty
      acids increased (palmitic acid greater-than-or-equal oleic acid > linoleic acid >
      EPA) and the inverse relationship held whether or not cholesterol was included in
      the culture media. The relative differences were very similar for the three
      stages of expression indicating that modulation of the LDL receptor by the fatty
      acids occurred at the level of gene transcription. The increased susceptibility
      to oxidation of the polyunsaturated fatty acids was unlikely to be a factor in
      the effect because EPA and linoleic acid (250 &mgr;M) still downregulated the LDL
      receptor in the presence of the antioxidant vitamin E (50 &mgr;M). In conclusion,
      the polyunsaturates, linoleic acid and EPA, effectively downregulated the LDL
      receptor of HepG2 cells compared to palmitic acid. The effects of these fatty
      acids were observed at the level of LDL receptor binding activity, protein and
      mRNA, strongly suggesting that the fatty acid effects were at the level of gene
      transcription.

PMID- 11834221
TI  - Exogenous myristic acid acylates proteins in cultured rat hepatocytes.
AB  - Fatty acid acylation is a functionally important modification of proteins. In the
      liver, however, acylated proteins remain largely unknown. This work was aimed at
      investigating fatty acid acylation of proteins in cultured rat hepatocytes.
      Incubation of these cells with [9,10-3H] myristic acid followed by two
      dimensional electrophoresis separation of the delipidated cellular proteins and
      autoradiography evidenced the reproducible and selective incorporation of
      radioactivity from the precursor into 18 well-resolved proteins in the 10--120
      kDa range and the 4--7 pH range. Radiolabeling of these proteins resulted from
      covalent linkage to the precursor [9,10-3H] myristic acid or to its elongation
      product, palmitic acid. The majority of the covalent linkages between the
      proteins and the fatty acids were broken by base hydrolysis, which indicated that
      the linkage was of thioester or ester-type. Only one of the studied proteins was
      attached to myristic acid via an amide linkage which resisted the basic treatment
      but was broken by acid hydrolysis. After incubation with [9,10-3H] palmitic acid,
      only two proteins previously detected with myristic acid were radiolabeled.
      Finally, the identified acylated proteins may be grouped into two classes:
      proteins involved in signal transduction (the alpha subunit of a heterotrimeric G
      protein and several small G proteins) and cytoskeletal proteins (cytokeratins,
      actin).

PMID- 11834222
TI  - Elevated plasma total homocysteine levels in hyperinsulinemic obese subjects.
AB  - Homocysteine has been associated with the oxidative stress in the pathogenesis of
      atherosclerosis. Oxidative stress caused by triglycerides and free fatty acids is
      known to cause insulin resistance and hyperinsulinemia. On the other hand,
      insulin resistance may increase homocysteine levels. Since obesity is associated
      with insulin resistance and hyperinsulinemia, we aimed to study the possible
      association of homocysteine with hyperinsulinemia in obese subjects. 20 obese
      male subjects (body mass index >29), aged 33--55 (mean 45 years old) were
      studied. A fasting blood sample was obtained for the study and the subjects
      undertook an oral glucose tolerance test with samples taken at 1 and 2 h after
      glucose. Subjects were divided in two groups according to the fasting insulin
      levels, < 9 &mgr;U/ml or normoinsulinemic (group 1) and >9 &mgr;U/ml or
      hyperinsulinemic (group 2). Glucose, insulin, homocysteine, folate, B(12,) total
      cholesterol, HDL-cholesterol and triglycerides levels were determined in fasting
      blood samples. In oral glucose tolerance test, glucose, insulin and homocysteine
      levels were measured. Hyperinsulinemic obese subjects (group 2) had higher levels
      of insulin and glucose at 1 h and 2 h postglucose, compared with group 1. Fasting
      total homocysteine and triglyceride levels were also increased in this group,
      whereas folate and B(12) levels were similar in both groups. Fasting homocysteine
      significantly correlated with fasting insulin (r = 0.6, p <0.01). Homocysteine
      levels slightly but significantly decreased after glucose loading in
      normoinsulinemic but not in hyperinsulinemic obese subjects. These results show
      that higher homocysteine levels are observed in the hyperinsulinemic obese
      subjects and suggest that homocysteine could play a role in the higher risk of
      cardiovascular disease in obesity.

PMID- 11834223
TI  - Gastrointestinal enzyme production of bioactive peptides from royal jelly protein
      and their antihypertensive ability in SHR.
AB  - In order to clarify the potential physiological function of royal jelly (RJ), we
      report here the gastrointestinal enzyme production of antihypertensive peptides
      from RJ. Intact RJ and its protein fraction did not retard the action of
      angiotensin I-converting enzyme (ACE) activity at all. However, development of
      ACE inhibition power of RJ was newly observed by pepsin hydrolysis (IC(50)=0.358
      mg protein/mL), and the subsequent trypsin and chymotrypsin hydrolyses
      (IC(50)=0.099 mg protein/mL). Single oral administration of this gastrointestinal
      RJ hydrolysate (1 g/kg dose) in 10-week spontaneously hypertensive rat resulted
      in a significant reduction of systolic blood pressure of 22.7 plus minus 3.6 mmHg
      at 2 hr (P<0.05 vs. 0 hr by one-way ANOVA, n=7). Then, the RJ hydrolysate was
      fractionated with gel permeation chromatography to obtain the di- and tri
      peptides (DTP) fraction. As a result of isolation from the DTP fraction by
      reversed phase-high performance liquid chromatography, eleven ACE inhibitory
      peptides were isolated from the DTP-RJ hydrolysate. Some of the ACE inhibitors
      were derived from the RJ-glycoprotein; eight peptides with the IC(50) value of
      <10 &mgr;M were identified from natural resources for the first time.
      Consequently, RJ protein was thought to be a good resource of ACE inhibitory
      peptides produced by the gastrointestinal enzyme hydrolyses.

PMID- 11834224
TI  - Modulation of carbon tetrachloride-induced oxidative stress by dietary fat in
      rats(open star).
AB  - Oxidative stress is believed to be involved in the pathophysiology of a number of
      chronic diseases including atherosclerosis, diabetes, and cataracts and to
      accelerate the aging process. The aim of this study was to elucidate the role of
      various dietary fats in the in vivo modulation of CCl(4) induced oxidative stress
      using rat as a model. Rats were raised on diets enriched with saturated (Beef
      Tallow), n-9 (Sunola oil), n-6 (Safflower oil) or n-3 (Flaxseed oil) fatty acids
      and exposed to elevated oxidative stress by administration of CCl(4.) Plasma
      concentration of 8-iso-PGF(2alpha), antioxidant micronutrients and antioxidant
      enzymes were measured to examine changes to oxidative stress subsequent to the
      administration of CCl(4). The fatty acid profiles of plasma and RBC membranes
      reflected the fats fed in the different diets. CCl(4) administration had no
      significant effect on fatty acid composition of plasma or RBC lipids. Plasma 8
      iso-PGF(2alpha) concentrations were elevated by CCl(4) administration regardless
      of the dietary fat fed. Within the induced oxidative groups the 8-iso-PGF(2alpha)
      concentrations were highest in Safflower oil followed by Sunola oil, Tallow and
      finally Flaxseed oil. Induction of oxidative stress by CCl(4) administration was
      associated with a significant reduction in Vitamin A content reaching a
      significantly lower concentration (P <0.05) in the Tallow and Flaxseed oil
      groups. Vitamin E concentrations were significantly lower (p = 0.01) in the
      Safflower oil and the Flaxseed oil than in the Tallow diet group following CCl(4)
      administration. Superoxide Dismutase (SOD) and Glutathione Peroxidase (GSHPx)
      activities were not affected by dietary fat manipulation. The results of this
      study indicate that dietary fat can modulate lipid peroxidation and antioxidant
      defenses when exposed to a pro-oxidant challenge.

PMID- 11834225
TI  - Green tea flavonoids inhibit the LDL oxidation in osteogenic disordered rats fed
      a marginal ascorbic acid in diet.
AB  - Osteogenic Disorder Shionogi (ODS) rats can not synthesize ascorbic acid (AA). We
      have examined the capacity of green tea flavonoids (GTF) to modify low-density
      lipoprotein (LDL) oxidation in ODS rats with dietary AA restriction. In the first
      experiment, ODS rats were fed diets containing 300 (AA300 diet) or 0 (AA0 diet)
      mg AA/kg diets for 20 d. In comparison with the AA300 diet, the AA0 diet
      significantly decreased the concentrations of plasma AA and alpha-tocopherol in
      LDL and significantly shortened the lag time of LDL oxidation in vitro. In the
      second experiment, ODS rats were fed one of the following three diets: the AA300
      diet, the diet containing 25 mg AA (AA25, marginal AA)/kg diet (AA25 diet), or
      the diet containing 25 mg AA + 8 g GTF/kg diet (AA25 + GTF diet) for 20 d. Plasma
      AA concentration were significantly lower in rats fed AA25 compared with AA300
      but not in those fed AA25 + GTF. LDL oxidation lag time was significantly longer
      in rats fed AA25 + GTF compared with the other two groups. Lag time for LDL
      oxidation was significantly and positively correlated with LDL alpha-tocopherol
      (r = 0.6885, P = 0.0191). These results suggest that dietary flavonoids suppress
      the LDL oxidation through the sparing effect on LDL alpha-tocopherol and/or
      plasma AA when AA intake is marginal in the ODS rats.

PMID- 11834226
TI  - Green tea protection of hypoxia/reoxygenation injury in cultured cardiac cells.
AB  - Antioxidant-rich diets exert a protective effect in diseases involving oxidative
      damage. Among dietary components, green tea is an excellent source of
      antioxidants. In this study, cultured neonatal rat cardiomyocytes were used to
      clarify the protective effect of a green tea extract on cell damage and lipid
      peroxidation induced by different periods of hypoxia followed by reoxigenation.
      Cultures of neonatal rat cardiomyocytes were exposed to 2--8 hr hypoxia,
      eventually followed by reoxygenation, in the absence or presence of alpha
      tocopherol or green tea. LDH release and the production of conjugated diene
      lipids were measured, and appeared linearly related to the duration of hypoxia.
      During hypoxia, both LDH release and conjugated diene production were reduced by
      alpha-tocopherol and, in a dose dependent manner, by green tea, the 50 &mgr;g/ml
      being the most effective dose. Reoxygenation caused no further increase in LDH
      leakage, while it caused a significant increase in conjugate dienes, which
      absolute value was lower in antioxidant supplemented cells. Anyway, the ratio
      between conjugated diene production after hypoxia and after reoxygenation was
      similar in all groups, indicating that the severity of free radical-induced
      reoxygenation injury is proportional to the severity of previous hypoxic injury.
      Since hypoxic damage is reduced by alpha-tocopherol and green tea, our data
      suggest that any nutritional intervention to attenuate reoxygenation injury must
      be directed toward the attenuation of the hypoxic injury. Therefore,
      recommendations about a high dietary intake of antioxidants may be useful not
      only in the prevention, but also in the reduction of cardiac injury following
      ischemia.

PMID- 11834227
TI  - Nutritionally induced adipose hypertrophy in young pigs is transient and
      independent of changes in the expression of the obese and peroxisome proliferator
      activated receptor genes.
AB  - Previous studies have shown that piglets weaned to a liquid milk replacer (MR),
      rather than a typical dry diet (DD) regimen, have improved growth rates and
      deposit more energy as body fat. In the present study, we used this model to
      determine whether changes in the expression of genes linked to the regulation of
      adiposity were related to the accelerated fat accretion. We also determined
      whether the increase in body fat was sustained throughout a substantial
      proportion of the growth curve. At weaning (19 plus minus 2 days of age), 96
      piglets were placed in 12 replicate pens per diet (4 pigs per pen, 2 barrows and
      2 gilts), and fed a liquid MR or conventional DD regimen for 5 weeks. Thereafter,
      6 barrows and 6 gilts pigs from each diet were killed for determination of whole
      body chemical composition (less gastrointestinal contents). The remaining pigs
      were assigned randomly to weight target groups (60, 85, and 110 kg), placed in
      individual pens, and fed a conventional dietary regimen until killed at their
      respective weight targets for tissue sampling and determination of whole body
      chemical composition. Over the 5-week period in which the MR was fed, the growth
      rate of the pigs consuming the MR exceeded that of the pigs fed the DD by 36% (P
      <.05). Fat gain in these pigs was increased to 1.8 times that of the pigs fed the
      DD, and percentage body fat was 45% greater (P <.05). Acetyl Co-A carboxylase
      (ACC) activity (per mg of adipose extract protein) was not different between the
      two diet groups at the conclusion of the 5-week period, or at 110 kg body weight.
      During the MR period, actual protein gain was increased (P <.05) 22% in the pigs
      fed the MR as well. By 110 kg of body weight, body fat was reduced (P <.05) by
      7.7% (total fat mass) and 8.3% (percentage of body weight basis) in the pigs fed
      MR vs. the DD group. The expression of the peroxisome proliferator activated
      receptors (PPAR) alpha and gamma was not influenced by diet or by body weight.
      Expression of the obese gene was independent of diet, but was greater (P <.09) in
      pigs at 110 kg body weight than at 60 kg. These data provide additional evidence
      that piglets weaned to liquid diets have greater rates of growth and deposit more
      body fat, but that this difference subsides quickly when a typical dry dietary
      regimen is imposed. Furthermore, the biochemical changes responsible for the
      increased adiposity are independent of changes in the expression of the obese or
      PPAR genes, at least at the mRNA level.

PMID- 11834228
TI  - Rapid suppression of protein degradation in skeletal muscle after oral feeding of
      leucine in rats.
AB  - A diet containing adequate amounts of protein rapidly suppresses myofibrillar
      protein degradation in rats and mice. This study determined whether dietary amino
      acids inhibit postprandial protein degradation in rat skeletal muscle. When rats
      fed on a 20% casein diet for 1 h after 18 h starvation, the rate of myofibrillar
      protein degradation measured by N(tau)-methylhistidine release from the isolated
      extensor digitorum longus muscle was significantly (p < 0.05) decreased at 4 h
      after refeeding. A diet containing an amino acid mixture which is the same
      composition as casein also reduced myofibrillar protein degradation at 4 h after
      refeeding (p < 0.05). An essential amino acid mixture (15.1%, corresponding to
      casein composition) and a leucine (2.9%) diets reduced the rate of myofibrillar
      protein degradation after refeeding (p < 0.05), whereas a protein free diet did
      not. Administration of leucine alone (0.135 g/100 g body weight) by a feeding
      tube induced a decrease in the rate of myofibrillar protein degradation at 2 h
      after administration (p < 0.05), whereas the serum insulin concentration was
      constant after leucine administration. These results suggested that leucine is
      one of regulating factors of myofibrillar protein degradation after refeeding of
      a protein diet.

PMID- 11834230
TI  - Emergency contraception in South Africa: knowledge, attitudes, and use among
      public sector primary healthcare clients.
AB  - To determine knowledge of, attitudes toward, and use of emergency contraception
      (EC), interviews were held with 1068 clients of 89 public sector primary
      healthcare facilities in two urban and two rural areas of South Africa. Only
      22.8% of the clients had heard of EC. Awareness was significantly lower in the
      most rural area and among older, less educated women. Knowledge of EC was
      superficial, with 47.1% unsure of the appropriate interval between unprotected
      intercourse and starting EC and 56.6% not knowing whether it was available at the
      clinic. Few (9.1%) of those who knew of EC had used it. After explaining EC,
      attitudes toward its use were found to be positive, with 90.3% indicating that
      they would use it if needed. Awareness was lower than in developed countries, but
      higher than in other developing countries. Findings indicate that if women know
      of EC, where to get it, and how soon to take it, they would use it if needed.

PMID- 11834229
TI  - The pharmacokinetics of 750 microg levonorgestrel following administration of one
      single dose or two doses at 12- or 24-h interval.
AB  - The administration of two tablets of 750 microg levonorgestrel at a 12- to 24-h
      interval has been shown to be a safe and effective means of emergency
      contraception, and Norlevo/Vikela (N/V) is a dedicated product for this
      indication. The aim of this study was to characterize the plasma pharmacokinetics
      of levonorgestrel following a single N/V tablet administration and following a
      second administration, 12 or 24 h after the first one in young, healthy, female
      volunteers under the same conditions as during clinical use. This was an open,
      observer-blind, randomized study with three parallel groups and three treatments
      performed in 24 white female volunteers randomized into three groups of eight
      participants, each receiving one of the following treatments: Group A, one tablet
      of 750 microg levonorgestrel at time -12 h and one tablet at time 0; Group B, one
      tablet of 750 microg levonorgestrel at time 0; Group C, one tablet of 750 microg
      levonorgestrel at time -24 h and one tablet at time 0. All treatments started
      between Day 2 and Day 6 of the menstrual cycle. Plasma levonorgestrel levels were
      measured at regular intervals from time 0 up to 36 h with a validated
      radioimmunoassay. The results of this study show that after either one single or
      two administrations of a tablet containing 750 microg levonorgestrel,
      levonorgestrel is rapidly absorbed. The absorption, distribution, and elimination
      profiles of levonorgestrel following the three different treatments were similar.
      It also indicates that 12 or 24 h after administration there remains a
      significant level of plasma levonorgestrel. In conclusion, this study reinforces
      clinical guidelines recommending that N/V tablets for emergency contraception be
      administered 12 to 24 h apart because levonorgestrel is present in plasma between
      the two administrations.

PMID- 11834231
TI  - Mifepristone abortion in minors.
AB  - Approximately one-third of pregnant teenagers in the U.S. choose abortion. This
      prospective study evaluated whether medical abortion with mifepristone and
      misoprostol is physically and emotionally acceptable in adolescents. Adolescents
      14- to 17-years-old, with pregnancies < or =56 days gestation, and seeking
      abortion services with parental consent from at least one parent were enrolled.
      Mifepristone (200 mg) was administered, followed 2 days later by 800 microg of
      misoprostol administered vaginally. Follow-up visit occurred on Day 4-8 to
      confirm abortion completion. Questionnaires regarding acceptability of the
      procedure as well as emotional coping were administered at the initial visit, at
      the follow-up visit, and by phone at 4 weeks postabortion. All 28 adolescents had
      complete medical abortions without complications or surgical intervention, and
      five minors did not require misoprostol. At the Day 4-8 follow-up visit, 75% of
      teens found the procedure acceptable, and that increased to 96% by the 4-week
      visit. Although 57% reported stress and 43% reported fear initially, by 4 weeks
      postabortion only 21% of the teens reported stress, and 8% were still
      experiencing fear. In addition, the minors' satisfaction with their abortion
      decision increased from 43% to 79% by 4 weeks postabortion. Medical abortion with
      mifepristone and misoprostol was highly effective and well tolerated, physically
      and emotionally, by adolescents in our sample. A larger clinical trial is needed
      to generalize these findings to other adolescent populations seeking medical
      abortion services.

PMID- 11834232
TI  - First trimester surgical abortion practices: a survey of National Abortion
      Federation members.
AB  - The objective of this study was to survey first trimester surgical abortion
      practices of North American providers. A survey was mailed to the 310 active
      member clinics of the National Abortion Federation, the professional organization
      of abortion providers in North America. The 236 respondents (76%) comprising the
      study group provided approximately 30% and 33% of all first trimester abortions
      in the US and Canada, respectively. Of the 529 practitioners who perform most
      abortions at the clinics, 68% are obstetrician-gynecologists, and 18% are family
      physicians; 51% are at least 50 years old. The majority of respondents (156 of
      236, 66%) confirm gestational age with ultrasonography. Of the 202 clinics that
      favor one method of anesthesia, 58% use local cervical block with or without oral
      pre-medication, 32% combine local anesthesia with intravenous sedation, and 10%
      use general anesthesia. Most clinics open the cervix with tapered dilators (207
      of 233, 89%), evacuate the uterus by using curved rigid plastic cannulas (157 of
      229, 69%) and an electric vacuum source (191 of 233, 82%), and explore the uterus
      with a metal curette following aspiration (133 of 232, 57%). A large majority of
      respondents examine the uterine aspirate on-site (91%), prescribe antibiotics
      (91%), and offer oral contraceptives (95%) when requested. Although variations
      exist, surgical techniques and postoperative practices are quite uniform among
      clinics. Local anesthesia is presently the most frequent method of pain control.
      Ultrasonographic dating before abortion is common practice. The "graying" of
      skilled practitioners raises concerns about the future availability of abortion.

PMID- 11834233
TI  - Third-generation progestogen type influences hemostatic changes caused by oral
      contraceptives in Brazilian women.
AB  - We compared the effects of two third-generation progestogens, desogestrel (DSG)
      and gestodene (GSD), on coagulation and fibrinolysis in Brazilian users of oral
      contraceptives (OCs). Forty-six women were evaluated before treatment and after
      six cycles of treatment. The coagulation, anticoagulant, and fibrinolytic systems
      were investigated. During the use of the DSG-containing OC, the activity of
      factors VII, VIII, IX, X, and XII increased significantly whereas the GSD
      containing OC caused no changes in coagulation parameters. Concerning the
      anticoagulant pathways, the DSG-containing OC increased protein C levels and
      decreased total protein S levels, and the GSD-containing OC only decreased total
      protein S. Both OCs increased plasminogen activity, although the DSG-containing
      OC increased fibrin degradation products levels and decreased the tissue
      plasminogen activator antigen. In conclusion, we have found that in Brazilian
      women the effects of DSG and GSD on hemostatic parameters are different and,
      therefore, third-generation progestogens may not contribute equally to the
      thrombotic risk.

PMID- 11834234
TI  - Effect of two oral contraceptives with different ethinyl estradiol and
      levonorgestrel concentrations on the urinary excretion of biochemical vasoactive
      markers.
AB  - In the present study the effect on the urinary excretion of vasoactive markers of
      two oral contraceptives (OCs), i.e., Leios, containing 0.02 mg ethinyl estradiol
      and 0.1 mg levonorgestrel, and Stediril 30, containing 0.03 mg ethinyl estradiol
      and 0.15 mg levonorgestrel, was investigated. cGMP, prostacyclin and its
      antagonist thromboxane, serotonin, and urodilatin, a natriuretic and diuretic
      peptide formed in the kidney, were measured as markers. In a comparative, double
      blind, randomized, parallel group study, 34 women received Leios and 33 women
      Stediril 30. Nocturnal urine was collected before treatment and during cyclic
      treatment after 3 and 12 cycles. Both contraceptives significantly enhanced cGMP
      excretion after 12 cycles. The prostacyclin metabolite remained unchanged for
      both formulations, but the excretion of the thromboxane metabolite was
      significantly decreased after 12 cycles. Thus, the ratio of prostacyclin to
      thromboxane, crucial for the resulting effect on vascular tone, increased
      significantly. For the serotonin metabolite, no changes were observed for both
      contraceptives. The excretion of urodilatin significantly increased for both
      preparations after 12 cycles compared to the pretreatment values. These results
      indicate that the low-dose OCs Leios and Stediril 30 may stimulate the production
      of some vasoactive markers, at least after 12 cycles of treatment. The positive
      influence of these contraceptives on the various markers investigated may improve
      vascular tone, impede development of atherosclerosis and arterial thrombosis, and
      improve water and electrolyte homeostasis. These effects most likely can be
      attributed to the estrogenic component. Levonorgestrel may elicit no impact on
      these estrogen-induced changes that, however, seem only to be manifested after a
      longer treatment period.

PMID- 11834236
TI  - Contraceptive efficacy and clinical performance of Nestorone implants in
      postpartum women.
AB  - The objective of this study was to evaluate the contraceptive efficacy and
      clinical performance of a Nestorone subdermal implant (NES) in the postpartum
      period. NES (n = 100) and Copper T intrauterine device (T-Cu; n = 100) acceptors
      initiated contraception at 8 weeks postpartum and were followed at monthly
      intervals during the first year and at 3-month intervals thereafter. Pregnancy
      rates, breastfeeding performance, infant growth, bleeding pattern, and side
      effects were assessed. Blood and milk NES concentration were measured. No
      pregnancy occurred in 2195 and 2145 woman-months of NES implant and T-Cu use,
      respectively. No effect of NES on lactation and infant growth and no serious
      adverse events were observed. Lactational amenorrhea was significantly longer in
      NES users (353 +/- 20 days) than in T-Cu users (201 +/- 11 days). More NES users
      (55.8%) experienced prolonged bleedings than did T-Cu users (36.2%).
      Concentrations of NES in breast milk ranged between 54-135 pmol/liter. The
      Nestorone implant is a highly effective contraceptive, safe for breastfed infants
      because the steroid is inactive by the oral route.

PMID- 11834235
TI  - Delayed first injection of the once-a-month injectable contraceptive containing
      25 mg medroxyprogesterone acetate and 5 mg estradiol-cypionate: effects on
      cervical mucus.
AB  - The objectives of this study were to assess whether women who were administered
      the first injection of the once-a-month contraceptive containing estradiol
      cypionate and 25 mg depot-medroxyprogesterone acetate (MPA+E(2)C) on Day 7 of
      their menstrual cycle (delayed injection) exhibit the same degree of cervical
      mucus changes as women who receive it on Day 5 of their menstrual cycle. This was
      a multicenter, randomized, controlled clinical trial. A total of 158 women, aged
      between 18 and 38 years (inclusive), who, were willing to use MPA+E(2)C as their
      contraceptive method participated in the trial. Participants received a MPA+E(2)C
      injection on Day 5 (control group, n = 41) or Day 7 (delayed-injection group, n =
      117) of their menstrual cycle. Participants who received MPA+E(2)C on Day 5 of
      their menstrual cycle (control group) exhibited fair or poor mucus quality and
      poor sperm penetration. Of those women who received MPA+E(2)C on Day 7 of their
      menstrual cycle (delayed-injection group), 3 (3%) showed good mucus or good sperm
      penetration at some time point during follow-up. It is possible to conclude that
      the first injection of MPA+E(2)C given on Day 7 of a menstrual cycle does not
      provide the same degree of inhibition of mucus quality and sperm penetration as
      that observed if it is administered on Day 5. However, the theoretical risk of
      pregnancy after receiving MPA+E(2)C on Day 7 would be expected to be low.

PMID- 11834237
TI  - Cellulose sulfate: tolerance and acceptability of penile application.
AB  - Sodium cellulose sulfate (CS) is under development as a vaginal microbicide and
      spermicide. This was a Phase I, randomized, double-blind study of men to assess
      acceptability, safety, and degree of penile irritation of seven consecutive daily
      doses of CS compared to an active control containing nonoxynol-9 (Conceptrol).
      The data suggest that CS gel is not more irritating to the male genitalia than
      Conceptrol. This, along with the minimal irritation seen in a Phase I safety
      study in women following 6 consecutive days of vaginal administration, suggests
      that CS could be used in future studies, without undue risk, where couples engage
      in vaginal intercourse. Male volunteers in future studies should be informed that
      1 out of 24 participants in the CS group in this study experienced tingling and
      slight stinging for a brief time after exposure compared with 3 out of 12 in the
      Conceptrol group who reported similar symptoms.

PMID- 11834238
TI  - Single and multiple exposure tolerance study of cellulose sulfate gel: a Phase I
      safety and colposcopy study.
AB  - Vaginally applied gels offer a promising approach for preventing unwanted
      pregnancies and sexually transmitted infections. Cellulose sulfate (CS) is a non
      cytotoxic antifertility agent that also exhibits in vitro antimicrobial activity
      against sexually transmitted pathogens, including HIV. This was a randomized,
      double-blinded, Phase I study of 2.5 mL and 5.0 mL doses of 6% CS gel. A single
      vaginal application of the gel followed by five consecutive daily doses was
      assessed for genital irritation, safety, vaginal leakage, and product
      acceptability compared to two controls, Conceptrol, which is a marketed
      contraceptive gel containing nonoxynol-9, and K-Y jelly. The results suggest that
      the safety of 6% CS was comparable to that of Conceptrol and K-Y jelly, and it
      may be associated with less genital irritation. The 2.5 mL dose of CS may be
      preferable according to the participants' reports of leakage. All the products
      had similar acceptability profiles.

PMID- 11834239
TI  - Comparison of the rheological properties of Advantage-S and Replens.
AB  - The rheological properties of Advantage-S and Replens were measured at body (37
      degrees C) and room temperature (25 degrees C) over a range of physiologically
      relevant shear rates. The viscosity of Replens was found to differ from that of
      Advantage-S, particularly at room temperature. In addition, the two materials
      differed in their miscibility with a vaginal fluid simulant.

PMID- 11834240
TI  - Possible involvement of oxidative stress in hypoxia-induced adrenomedullin
      secretion in cultured rat cardiomyocytes.
AB  - Although hypoxia induces adrenomedullin gene expression in cultured rat cardiac
      myocytes, it is still unknown whether oxidative stress is involved in the hypoxia
      induced adrenomedullin production. We investigated whether oxidative stress might
      participate in hypoxia-induced adrenomedullin secretion and whether
      adrenomedullin might have a protective effect on damaged myocytes. Hypoxia
      increased adrenomedullin secretion and its gene expression in cardiac myocytes,
      but not in nonmyocytes. Furthermore, oxidative stress (hydrogen peroxide) also
      increased adrenomedullin secretion from myocytes. N-acetyl-L-cysteine, a free
      radical scavenger, completely inhibited the stimulation of adrenomedullin
      secretion by hydrogen peroxide, and this agent reduced the stimulation of
      adrenomedullin secretion by hypoxia. Lactate dehydrogenase leakage, a marker of
      cell injury, was significantly increased with the exposure to hydrogen peroxide
      and adrenomedullin significantly reduced this leakage. These findings suggest
      that an oxidative stress may be involved, in part, in the increased
      adrenomedullin secretion from cardiac myocytes under hypoxic condition.
      Adrenomedullin secreted from myocytes may play a cell protective role in an
      autocrine manner.

PMID- 11834241
TI  - Troglitazone suppresses cell growth of KU812 cells independently of PPARgamma.
AB  - We examined the effects of troglitazone, one of thiazolidinedione derivatives on
      human basophilic leukemia cell line KU812. Troglitazone caused the suppression of
      cell growth, which was suggested to result from the decrease in cyclin E and the
      hyperphosphorylated form of retinoblastoma tumor suppressor gene product (pRb).
      In addition, troglitazone caused a decrease in histamine secretion due to the
      reduced expression of histidine decarboxylase mRNA. Peroxisome proliferator
      activated receptor (PPAR)-gamma mRNA was undetectable by reverse transcription
      polymerase chain reaction (RT-PCR) in KU812 cells. These findings suggested that
      troglitazone suppressed cell growth and histamine synthesis independently of
      PPARgamma.

PMID- 11834242
TI  - Involvement of Rho and tyrosine kinase in angiotensin II-induced actin
      reorganization in mesothelial cells.
AB  - We investigated the role of angiotensin II type 1 (AT(1)) receptors in
      angiotensin II-induced actin reorganization and the signaling pathways of the
      response in pleural mesothelial cells. The effects of angiotensin II on actin
      reorganization in pleural mesothelial cells were evaluated by dual fluorescence
      labeling of filamentous (F) and monomeric (G) actin with fluorescein
      isothiocyanate (FITC)-labeled phalloidin and Texas Red-labeled DNase I,
      respectively. Angiotensin II (10 microM) induced actin reorganization in the
      presence and the absence of extracellular Ca(2+). An angiotensin AT(1) receptor
      antagonist ([Sar(1),Ile(8)]angiotensin II) inhibited angiotensin II-induced actin
      reorganization. Pretreatment with C3 exoenzyme or tyrosine kinase inhibitors
      significantly reduced angiotensin II-induced actin reorganization. However,
      pertussis toxin, phosphatidylinositol-3-kinase and protein kinase C inhibitors
      had no effect on these responses. These results suggest that angiotensin II
      induced actin reorganization in pleural mesothelial cells is extremely dependent
      on the angiotensin AT(1) receptor coupled with pertussis toxin-insensitive
      heterotrimeric G proteins, Rho GTPases and tyrosine phosphorylation pathways.

PMID- 11834243
TI  - Molecular cloning and expression of the porcine trigeminal ganglion cDNA encoding
      a 5-ht(1F) receptor.
AB  - Using a combination of reverse transcription polymerase chain reaction (RT-PCR)
      and inverse-PCR techniques, we amplified, cloned and sequenced a full-length
      porcine 5-hydroxytryptamine 1F (5-ht(1F)) receptor complementary DNA (cDNA)
      derived from porcine trigeminal ganglion. Sequence analysis revealed 1101 base
      pairs (bp) encoding an open reading frame of 366 amino acids showing a high
      similarity (>90%) with the 5-ht(1F) receptor sequences from other species,
      including human. The recombinant porcine 5-ht(1F) receptor was expressed in
      African green monkey kidney cell lines (COS-7 cells) and its ligand binding
      profile was determined using [3H]5-HT. The affinities of several agonists
      (LY334370 (5-(4-fluorobenzoyl)amino-3-(1-methylpiperidin-4-yl)-1H-indole
      fumarate)>CP122638 (N-methyl-3 [pyrrolidin 2(R)-yl methyl]-1H-indol-5-ylmethyl
      sulphonamide)=naratriptan =5HT>eletriptan>sumatriptan>frovatriptan
      =avitriptan>dihydroergotamine>zolmitriptan>5
      carboxamidotryptamine>rizatriptan>alniditan=donitriptan>L694247 (2-[5-[3-(4
      methylsulphonylamino)benzyl-1,2,4-oxadiazol-5-yl]-1H-indole-3-yl] ethylamine) and
      putative antagonists (methiothepin>GR127935 (N-[4-methoxy-3-(4-methyl-1
      piperazinyl) phenyl]-2'-methyl 4'-(5-methyl-1,2,4-oxadiazol-3-yl) [1,1-biphenyl]
      4-carboxamide hydrochloride)>ritanserin>SB224289 (2,3,6,7-tetrahydro-1'-methyl-5
      [2'-methyl-4'(5-methyl-1,2,4-oxadiazol-3-yl) biphenyl-4-carbonyl] furo [2,3-f]
      indole-3-spiro-4'-piperidine hydrochloride)>BRL155572 ([1-(3-chlorophenyl)-4-[3,3
      diphenyl (2-(S,R) hydroxypropanyl)piperazine] hydrochloride)>ketanserin=pindolol)
      correlated highly with those described for the recombinant human 5-ht(1F)
      receptor (Spearman correlation coefficient; r(s)=0.942). Nevertheless, as
      compared to the human homologue, some triptans (i.e. sumatriptan, zolmitriptan
      and rizatriptan) displayed a 10- to 15-fold lower affinity for the porcine 5
      ht(1F) receptor. Using RT-PCR technique, the expression of porcine 5-ht(1F)
      receptor mRNA was observed in cerebral cortex, trigeminal ganglion and several
      blood vessels, but not in skeletal muscles. In conclusion, we have cloned and
      established the amino acid sequence and ligand binding profile of the porcine 5
      ht(1F) receptor as well as the distribution of its mRNA. This information may be
      helpful in exploring the role of 5-ht(1F) receptor in physiological processes and
      diseases, such as migraine.

PMID- 11834244
TI  - Binding of sigma receptor ligands and their effects on muscarine-induced Ca(2+)
      changes in SH-SY5Y cells.
AB  - In human neuroblastoma SH-SY5Y cell preparations, sigma(1) receptor agonists (+)
      pentazocine and 1S,2R-(-)-cis-N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(1
      pyrrolidinyl)cyclohexylamine (BD737) competed for [3H]haloperidol binding with
      K(i) values of 67+/-10 and 14+/-10 nM, respectively. (+)-Pentazocine or BD737 up
      to 10 microM did not affect basal levels of intracellular Ca(2+) concentration
      ([Ca(2+)](i)) in these cells, but they significantly reduced muscarine-induced
      [Ca(2+)](i) changes in a dose-related manner. However, the reduction by (+)
      pentazocine was not reversed by the sigma(1) receptor antagonist haloperidol.
      Further studies showed (+)-pentazocine, BD737 and haloperidol could compete for
      [3H]quinuclidinyl benzilate binding in SH-SY5Y cells with K(i) values of 0.51+/
      0.06, 0.32+/-0.07 and 4.4+/-2.3 microM, respectively. Thus, the inhibitory
      effects on muscarine-induced [Ca(2+)](i) changes by (+)-pentazocine and BD737 in
      SH-SY5Y cells were likely due to blockade of muscarinic receptors, not due to
      sigma(1) receptor activation by these ligands.

PMID- 11834245
TI  - Ambroxol inhibits platelet-derived growth factor production in human monocytic
      cells.
AB  - Several growth factors, including platelet-derived growth factor (PDGF), have
      been implicated in the mechanism of lung and airway remodeling. We investigated
      the effect of ambroxol, trans-4-[(2-amino-3,5-dibromobenzyl) amino] cyclohexanol
      hydrochloride, on the lipopolysaccharide-induced PDGF production in human
      monocytic cells, THP-1. Ambroxol inhibited the lipopolysaccharide-induced PDGF-AB
      production via PDGF-A mRNA expression. Lipopolysaccharide activated p44/42
      extracellular signal-regulated kinase (ERK), and ambroxol attenuated the
      lipopolysaccharide-induced p44/42 ERK activation. Furthermore, mitogen-activated
      protein kinase kinase (MEK)-1-specific inhibitor, 2-(2-amino-3-methoxyphenyl)-4H
      1-benzopyran-4-one (PD 98059), blocked the lipopolysaccharide-induced p44/42 ERK
      activation and PDGF production. These findings indicate that ambroxol inhibits
      the lipopolysaccharide-induced PDGF production due to the suppression of p44/42
      ERK activity.

PMID- 11834246
TI  - Microglial derived nitric oxide decreases serotonin content in rat basophilic
      leukemia (RBL-2H3) cells.
AB  - Nitric oxide (NO) and serotonin (5-hydroxytryptamine; 5-HT) are important
      neuromodulators that are involved in a myriad of biochemical reactions. In this
      work, we describe a novel model co-culture system to study the interactions
      between NO and 5-HT. NO derived from cytokine stimulated Bv2 microglial cells
      depleted 5-HT from RBL-2H3 cells. Reduction of 5-HT content by NO derived from
      the NO donor S-nitroso-N-acetylpenicillamine (SNAP) was concentration-dependent,
      independent of intracellular Ca(2+) and inhibited by reduced glutathione (GSH).
      Collectively, these data indicate that this cell co-culture system is a viable
      model to study the mechanisms of interaction between nitrergic and serotonergic
      pathways.

PMID- 11834247
TI  - Effects of chronically administered venlafaxine on 5-HT receptor activity in rat
      hippocampus and hypothalamus.
AB  - The effects of chronic administration of the mixed serotonin [5-hydroxytryptamine
      (5-HT)]/norepinephrine re-uptake inhibitor venlafaxine (5 mg/kg daily by osmotic
      minipump for 28 days) on the sensitivity of somatodendritic 5-HT(1A)
      autoreceptors on serotonergic neurons innervating the hypothalamus, and on 5
      HT(1B) autoreceptors in both hypothalamus and hippocampus, were determined using
      in vivo microdialysis in freely moving rats. Venlafaxine induced a reduction in
      sensitivity of 5-HT(1B) autoreceptors in hypothalamus, but did not affect the
      sensitivity of 5-HT(1A) autoreceptors, or of 5-HT(1B) autoreceptors in
      hippocampus. The corticosterone and oxytocin responses to the 5-HT(1A) receptor
      agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT, 0.05 or 0.2 mg/kg), a
      measure of postsynaptic 5-HT(1A) receptor activity in the hypothalamus, were
      reduced in animals administered 5 or 10 mg/kg venlafaxine daily by
      intraperitoneal injection for 21 days. This desensitization of post-synaptic 5-
      HT(1A) receptors in the hypothalamus may be a consequence of increased 5-HT
      levels induced by desensitization of the presynaptic 5-HT(1B) receptors. These
      results taken together with those of previous studies suggest that the
      hypothalamus might be an important site of drug action, and that venlafaxine has
      an overall mechanism similar to that of selective serotonin re-uptake inhibitors.

PMID- 11834248
TI  - Methiothepin attenuates gastric secretion and motility effects of vagal
      stimulants at the dorsal vagal complex.
AB  - Methiothepin, a nonselective 5-HT receptor antagonist was utilized to explore the
      5-HT modulation of dorsal vagal complex-TRH (thyrotropin releasing hormone)
      analogue stimulated gastric functional parameters. Intracisternal methiothepin
      pretreatment (200, 0.1 nmol) produced significant inhibition (70%, 44%,
      respectively) of the TRH analogue [p-Glu-His-(3,3'-dimethyl)-Pro NH2; RX 77368
      (12 pmol)]-induced gastric acid output compared to vehicle pretreatment.
      Intracisternal pretreatment with methysergide (nonspecific 5-HT receptor
      antagonist) or combined cyanopindolol (5-HT(1A and 1B) receptor
      antagonist)+ritanserin (receptor antagonist of the 5-HT(2) family) did not alter
      the dorsal vagal complex-RX 77368 response. Unilateral dorsal vagal complex
      pretreatment with methiothepin (50 nmol/50 nl) attenuated ipsilateral dorsal
      vagal complex-TRH analog (12 pmol) induced gastric secretory response by 57%. The
      gastric secretagogue response to stimulation of the raphe obscurus (mediated by
      TRH release into the dorsal vagal complex) was inhibited 50% by pretreatment with
      intracisternal dorsal medullary methiothepin (0.1 nmol/10 microl). Intracisternal
      methiothepin (200 nmol/20 microl) also attenuated (a) dorsal vagal complex
      glutamate (60 nmol/30 nl) stimulated gastric acid secretion and (b) gastric
      motility stimulated by dorsal vagal complex-RX 77368 (12 pmol/30 nl). The data
      suggest that other properties of methiothepin, alone or in addition to its 5-HT
      receptor antagonist effect, mediate its inhibitory actions at the dorsal vagal
      complex.

PMID- 11834249
TI  - Differential involvement of 5-HT(2A) receptors in the discriminative-stimulus
      effects of cocaine and methamphetamine.
AB  - Involvement of 5-HT(2A) receptors in the discriminative-stimulus effects of
      cocaine versus methamphetamine was studied in Sprague Dawley rats (n=10) trained
      to discriminate 10 mg/kg cocaine, i.p., from saline under a fixed-ratio 10 (FR10)
      schedule of food presentation. The ability of (+/-)-1-(2,5-dimethoxy-4
      iodophenyl)-2-aminopropane (DOI), a 5-HT(2A) receptor agonist, and ketanserin, a
      5-HT(2A) receptor antagonist, to either substitute for or block the
      discriminative-stimulus effects of cocaine, or to shift the cocaine dose-response
      curve, was evaluated. DOI (0.18-1.0 mg/kg) partially substituted for the training
      dose of 10 mg/kg cocaine, but only at doses that decreased rates of responding.
      At the highest dose of DOI tested (1.0 mg/kg), there was about 65% cocaine
      appropriate responding. Substitution of DOI for cocaine and DOI-induced decreases
      in rates of responding were completely reversed by ketanserin (3.0 mg/kg).
      Ketanserin (3.0 mg/kg) also produced a significant shift to the right of the
      cocaine dose-response curve and antagonized increases in rates of responding
      produced by lower doses of cocaine. Ketanserin (1.0-10.0 mg/kg), however, did not
      block the discriminative-stimulus effects of the training dose of cocaine. When
      DOI (0.3 mg/kg) was co-administered with different doses of cocaine, there was a
      slight leftward shift in the cocaine dose-response curve, which was not
      significant and appeared to reflect simple additive effects of DOI and cocaine.
      In contrast, the same dose of DOI (0.3 mg/kg) produced a marked and highly
      significant shift to the left of the methamphetamine (0.18-1.0 mg/kg) dose
      response curve in the same subjects and the effects of DOI and methamphetamine
      were clearly more than additive. The present findings provide new evidence that
      there is some serotonergic modulation of cocaine's discriminative-stimulus
      actions, which appears to involve stimulation of 5-HT(2A) receptors. However,
      involvement of 5-HT(2A) receptor activity in the discriminative-stimulus actions
      of cocaine appears to be less pronounced than in similar actions of
      methamphetamine.

PMID- 11834250
TI  - cGMP, but not cAMP, in rat hippocampus is involved in early stages of object
      memory consolidation.
AB  - The present study investigates the role of cGMP and cAMP on the memory
      performance in the object recognition task in rats. The analogue 8-Br-GMP or 8-Br
      cAMP was administered bilaterally into the hippocampus (0, 1, 3 and 10 microg in
      0.5 microl saline/site) immediately after the exposure to two identical objects.
      After 24 h, saline-treated animals spent equal times exploring a new and the
      familiar object demonstrating that they did not recognize the familiar one.
      However, a dose-dependent improvement in object recognition was found after
      injection of 8-Br-cGMP. In contrast, 8-Br-cAMP did not improve the memory
      performance at the doses tested. These results indicate that hippocampal cGMP but
      not cAMP is involved in early stages of consolidation of object memory.

PMID- 11834251
TI  - Involvement of alpha-calcitonin gene-related peptide in monophosphoryl lipid A
      induced delayed preconditioning in rat hearts.
AB  - Recent study has shown that monophosphoryl lipid A-induced delayed
      preconditioning enhanced preservation with cardioplegia and that the protective
      effects of monophosphoryl lipid A were related to stimulation of calcitonin gene
      related peptide (CGRP) release. The purpose of the present study was to explore
      whether the elevated release of CGRP induced by monophosphoryl lipid A is
      secondary to stimulation of CGRP synthesis via the nitric oxide (NO) pathway and
      to characterize the isoform of CGRP. Sprague-Dawley rats were pretreated with
      monophosphoryl lipid A 24 h before the experiment, and then the left main
      coronary artery of rat hearts was subjected to 1 h occlusion followed by 3 h
      reperfusion. Infarct size, plasma creatine kinase activity, the plasma level of
      CGRP, and the expression of CGRP isoforms (alpha- and beta-CGRP) mRNA in lumbar
      dorsal root ganglia were measured. Pretreatment with monophosphoryl lipid A (500
      microg/kg, i.p.) significantly reduced infarct size and creatine kinase release.
      Monophosphoryl lipid A caused a significant increase in the expression of alpha
      CGRP mRNA, but not of beta-CGRP mRNA, concomitantly with an increase in plasma
      concentrations of CGRP, and the increased level of CGRP expression happened
      before stimulation of CGRP release. The effect of monophosphoryl lipid A was
      completely abolished by pretreatment with L-nitroarginine methyl ester (L-NAME,
      10 mg/kg, i.p.), an inhibitor of NO synthase or capsaicin (50 mg/kg, s.c.), which
      selectively depletes transmitters in capsaicin-sensitive sensory nerves. The
      results suggest that the delayed cardioprotection afforded by monophosphoryl
      lipid A involves the synthesis and release of CGRP via the NO pathway, and that
      the protection is mainly mediated by the alpha-CGRP isoform.

PMID- 11834252
TI  - Fluvastatin reduces modification of low-density lipoprotein in hyperlipidemic
      rabbit loaded with oxidative stress.
AB  - The in vivo antioxidant effect of fluvastain, a 3-hydroxy-3-methylglutaryl
      coenzyme A (HMG-CoA) reductase inhibitor, was investigated using Watanabe
      heritable hyperlipidemic (WHHL) rabbits subjected to nicotine-free cigarette
      smoke extracts as oxidative stress. Fluvastatin was given orally at doses of 10
      and 30 mg/kg per day for 5 months. The cigarette smoke extracts were prepared by
      bubbling the gas phase of smoke into phosphate-buffered saline and was injected
      daily into the rabbit ear vein. The rabbits chronically treated with the
      cigarette smoke extracts showed an increase in plasma lipid peroxide levels,
      estimated as thiobarbituric acid-reactive substances. Oxidative modification of
      plasma low-density lipoprotein (LDL) was assessed by anion-exchange high
      performance liquid chromatographic analysis, LDL susceptibility to oxidation, LDL
      incorporation into macrophages and thiobarbituric acid-reactive substances levels
      in LDL. Treatment with fluvastatin significantly reduced these effects induced by
      the cigarette smoke extracts in a dose-related manner and exerted a cholesterol
      lowering effect. At the end of the experiment, the cigarette smoke extracts
      caused accumulation of cholesteryl ester in the thoracic aorta, while fluvastatin
      significantly prevented this accumulation. These results indicate that
      fluvastatin can exert an antioxidant effect in vivo, with a strong effect on
      oxidative stress such as smoking, a major risk factor of atherosclerosis.

PMID- 11834253
TI  - Venodilator action of an organotransition-metal nitrosyl complex.
AB  - Nitrovasodilators, such as nitroglycerin, cause endothelium-independent
      dilatation of arterial and capacitance vessels via the release of nitric oxide
      (NO). This study examined the venodilator effect of CpCr(NO)(2)Cl
      (organotransition-metal nitrosyl complex) relative to that of nitroglycerin in
      conscious, unrestrained rats. Organotransition-metal nitrosyl complexes have
      releasable NO directly attached to metal centres. The dose-response effects of
      CpCr(NO)(2)Cl and nitroglycerin on the mean arterial pressure and the mean
      circulatory filling pressure (index of the body venous tone) were obtained in
      rats continuously infused with either normal saline or noradrenaline. The results
      show that both CpCr(NO)(2)Cl and nitroglycerin reduced the mean arterial pressure
      in rats with normal or elevated vasomotor tone. However, maximum depressor
      response of CpCr(NO)(2)Cl was greater than that of nitroglycerin. In vehicle
      treated rats, both compounds increased the mean circulatory filling pressure. In
      rats with elevated vasomotor tone through the infusion of noradrenaline, both
      agents reduced the mean circulatory filling pressure. These results show that
      CpCr(NO)(2)Cl is an efficacious depressor and venodilator agent.

PMID- 11834254
TI  - Effects of the superoxide dismutase-mimetic compound tempol on endothelial
      dysfunction in streptozotocin-induced diabetic rats.
AB  - Evidence exists to support the beneficial effects of superoxide dismutase on
      endothelial dysfunction induced by hyperglycemia in vitro. In vivo, however,
      studies of the effects of native superoxide dismutase preparations on the
      vascular complications accompanying diabetes are limited, and their therapeutic
      application potential has so far been disappointing. The objective of this study
      was to evaluate, for the first time in vivo, the effects of long-term
      administration of tempol, a stable superoxide dismutase-mimic compound, on
      diabetes-induced endothelial dysfunction in rats. Diabetes was induced by
      streptozotocin and rats were monitored for 8 weeks with or without treatment with
      tempol (100 mg/kg, s.c., b.i.d). Diabetic rats showed increased vascular levels
      of superoxide, which was accompanied by increased levels of the oxidative stress
      markers malondialdehyde and 8-epi-prostaglandin F(2alpha). In addition, the
      vasorelaxant as well as the cGMP-producing effects of acetylcholine and glyceryl
      trinitrate were reduced in diabetic rats. Treatment with tempol abolished not
      only the differences in the vascular content of superoxide, malondialdehyde and 8
      epi-prostaglandin F(2alpha), but also the differences in the relaxation and cGMP
      responses of aortic rings to both acetylcholine and glyceryl trinitrate between
      control and diabetic rats. These results support the involvement of reactive
      oxygen species in mediation of hyperglycemia-induced endothelial dysfunction in
      vivo, and provide the rationale for potential utilization of stable superoxide
      dismutase-mimic nitroxides for the prevention of the vascular complications
      accompanying diabetes.

PMID- 11834256
TI  - Mechanisms of wood smoke-induced increases in nasal airway resistance and
      reactivity in rats.
AB  - We investigated the mechanisms of wood smoke-induced increases in nasal airway
      resistance (RNA) and airway reactivity in anesthetized rats. Delivery of wood
      smoke into a functionally isolated nasal airway produced an increase in RNA,
      which was attenuated by CP-96,345 [a tachykinin NK(1) receptor antagonist;
      (2S,3S)-cis-2-(diphenylmethyl)-N-((2-methoxyphenyl)-methyl)-1-azabicyclo(2.2.2.)
      octan-3-amine] or atropine. Additionally, smoke pre-exposure animals displayed a
      greater amplitude and a longer duration of RNA responses to capsaicin or
      histamine provocation, as compared to air controls. This enhanced airway
      reactivity to capsaicin or histamine was largely alleviated by CP-96,345 or
      atropine. The nasal secretory responses to capsaicin or histamine in smoke pre
      exposure animals were similar to those in air controls. We concluded that (1)
      reflex cholinergic and tachykininergic mechanisms play important roles in wood
      smoke-induced increases in nasal airway resistance and airway reactivity, and (2)
      this nasal airway hyperreactivity might not be due to an exaggerated secretory
      response, but is presumably due to augmented nasal swelling.

PMID- 11834255
TI  - Receptor preferences of cysteinyl-leukotrienes in the guinea pig lung parenchyma.
AB  - Two cysteinyl-leukotriene receptors, CysLT(1) and CysLT(2) receptors, have been
      cloned, but the contractions to cysteinyl-leukotrienes in the guinea pig lung
      parenchyma have been reported to be resistant to CysLT(2) receptor antagonism and
      to be only partially inhibited by CysLT(1) receptor antagonism. The receptor
      preferences of the individual cysteinyl-leukotrienes (leukotriene C(4), D(4) and
      E(4)) in the guinea pig lung parenchyma were studied in organ baths. CysLT(1)
      receptor antagonists competitively inhibited the contraction to leukotriene E(4),
      but exhibited only weak antagonism of contractions to leukotriene C(4) and D(4).
      In the presence of the cyclooxygenese inhibitor indomethacin and the nitric oxide
      synthase inhibitor N(omega)-nitro-L-arginine (L-NOARG), the CysLT(1) receptor
      antagonists did not further inhibit the leukotriene D(4)-induced contraction.
      These results suggest that leukotriene E(4) solely activates a CysLT(1) receptor,
      and that the CysLT(1) receptor antagonist-resistant contraction to leukotriene
      D(4) and C(4) is mediated via another CysLT receptor.

PMID- 11834257
TI  - Nucleotide-evoked relaxation of rat vas deferens: possible mechanisms.
AB  - ATP causes relaxation of the K(+)-contracted rat vas deferens. Possible sites of
      action were investigated. ATP and adenosine relaxed the vas deferens
      precontracted with 80 mM K(+); EC(50) values and maximal relaxations averaged,
      respectively, 760 microM and 56% for ATP and 74 microM and 30% for adenosine. The
      adenosine P1 receptor antagonist 8-(para-sulfophenyl)theophylline (8-SPT) reduced
      relaxations caused by adenosine and low concentrations of ATP, as did the Rp
      diastereomer of adenosine 3',5'-cyclic phosphorothioate (Rp-cAMPS), an inhibitor
      of protein kinase A. The phosphodiesterase inhibitor 4-(3-butoxy-4-methoxybenzyl)
      2-imidazolidinone (Ro 20-1724) augmented responses to adenosine and low
      concentrations of ATP. alpha,beta-Methylene ADP, an inhibitor of 5'-nucleotidase,
      reduced relaxations caused by ATP to a similar extent as did 8-SPT. In the
      presence of an almost saturating concentration of adenosine, ATP caused further
      relaxation. Conversely, in the presence of ATP, adenosine had little effect. Like
      ATP, UTP and other nucleoside triphosphates relaxed the vas deferens. The P2
      receptor antagonists reactive blue 2, acid blue 25 and 4,4'
      diisothiocyanotostilbene-2,2'-disulphonate (DIDS) attenuated the relaxation
      caused by ATP; suramin, pyridoxalphosphate-6-azophenyl-2',4'-disulphonate
      (PPADS), Evans blue, trypan blue, reactive red 2 and brilliant blue G had no
      effect. Three non-selective inhibitors of protein kinases, 1-(5
      isoquinolinesulfonyl)-2-methylpiperazine (H-7), staurosporine and (8R*,9S*,11S*)
      (-)-9-hydroxy-9-carboxy-8-methyl-2,3,9,10-tetrahydro-8,11-epoxy-1H,8H,11H
      2,7b,11a-triazadibenzo[a,g]cycloocta[cde]trinden-1-one (K-252b), markedly reduced
      the relaxation caused by ATP. The results indicate that adenosine, derived from
      enzymatic dephosphorylation, contributes to the relaxant effect of ATP,
      presumably by activation of a smooth muscle adenosine receptor linked to the
      accumulation of cAMP and activation of protein kinase A. Yet, the main part of
      the response to ATP is mediated by a site distinct from the adenosine receptor.
      The pharmacological properties of this site differ from known P2 receptor
      subtypes. Possibly, the nucleotide-evoked relaxation is due to a phosphoryl
      transfer catalyzed by an ecto-protein kinase.

PMID- 11834258
TI  - Inhibition of the renin-angiotensin system ameliorates genetically determined
      hyperinsulinemia.
AB  - This study was performed in order to assess the potentially different effects of
      the angiotensin-converting enzyme inhibitor captopril and of the angiotensin II
      receptor antagonist irbesartan on the metabolic syndrome in an animal model. Male
      NZO/BL6 F1 mice were treated with captopril, irbesartan, or placebo for 10
      months: Control animals treated with placebo developed a metabolic syndrome with
      obesity (55.5+/-6.3 g), hypertension (146+/-10 mm Hg), hyperinsulinemia (7.2+/
      5.7 ng/ml), hypercholesterolemia (5.1+/-0.7 mmol/l), cardiac hypertrophy (269+/
      44 mg) and atherosclerotic plaques in the ascending aorta (3.6+/-1.5 microm(2)).
      Treatment with angiotensin-converting enzyme inhibitor or angiotensin II receptor
      antagonist significantly (p<0.001) reduces hypertension (73+/-5 and 78+/-11 mm
      Hg), cardiac hypertrophy (203+/-26 and 202+/-18 mg) and atherosclerosis (2.2+/
      0.9 and 1.8+/-0.8 microm(2)). In addition, they prevented the development of
      obesity (42.2+/-3.5 and 38.3+/-2.8 g) and hyperinsulinemia (3.6+/-1.5 and 1.8+/
      0.4 ng/ml). In conclusion, long-term treatment with an angiotensin-converting
      enzyme inhibitor or an angiotensin II receptor antagonist can ameliorate obesity
      and hyperinsulinemia in a genetically determined mouse model.

PMID- 11834260
TI  - Clinical and radiological results of lumbar microdiskectomy technique with
      preserving of ligamentum flavum comparing to the standard microdiskectomy
      technique.
AB  - BACKGROUND: The ligamentum flavum is the anatomic plane between the epidural and
      laminar-extralaminar spaces, which should be meticulously preserved for a
      possible reoperation. Preservation of the ligamentum flavum together with other
      epidural anatomic structures, such as epidural fat tissue and venous plexuses,
      and limited removal of the lamina are important components in preventing epidural
      fibrosis that may be the cause of failed back surgery syndrome. METHODS: One
      thousand five hundred patients underwent microdiskectomy with preservation of the
      ligamentum flavum over an 8-year period. This technique was performed with a
      small incision using an 18 mm-width mini Taylor retractor. The ligamentum flavum
      was released and preserved as a 3-sided flap. The disk content was totally
      removed and a pediculated fat graft was used to cover the root at the end. Four
      hundred patients operated on with the ligamentum flavum preserving technique were
      randomly selected for this study (Group 1). Their results were compared with
      those of 200 patients who were operated on with the standard microdiskectomy
      (Group 2). Standard microdiskectomy technique was performed with fenestration and
      foraminotomy and the ligamentum flavum was partially or totally excised. Early
      clinical outcome was classified as excellent, good, fair, poor, or failure. The
      clinical mean follow-up period in Group 1 was 36.8 months and in Group 2 it was
      32.4 months. One hundred patients from each group had computed tomographic scans
      with contrast administration performed at least one year after the operation to
      examine late epidural fibrosis. A questionnaire was given to all patients at
      least 3 times during the late follow-up period. The questionnaire required
      patients to describe their relief of pain, job performance, and abstinence from
      narcotic analgesic use. RESULTS: Early clinical outcome (fourth postoperative
      week) in Group 1 was satisfactory in 96.75% of the patients, whereas it was
      satisfactory in only 81.5% in Group 2 (p < 0.001). The radiological examinations
      revealed fibrosis in 18% of the patients in Group 1 and 37% in Group 2 (p <
      0.001). None of the patients in Group 1 were readmitted because of fibrosis
      related symptoms. The reoperation rate in Group 1 was 4.5%. The recurrence rate
      was 1.75% and disc at another level was 2.5%. One patient was reoperated because
      of a suture granuloma. In Group 2, the reoperation rate was 9% (p < 0.05). The
      recurrence rate was 4.5%, disc at another level was 3.5% and extensive epidural
      fibrosis was 1%. Two patients who underwent surgery for epidural fibrosis in this
      group had disappointing outcomes. Overall success rate based on the questionnaire
      was 91% in Group 1 and 76% in Group 2 (p < 0.001). CONCLUSIONS: The ligamentum
      flavum preserving technique is useful in achieving a favorable long-term outcome,
      and reoperation, if necessary, is easier and safer.

PMID- 11834263
TI  - Emergency diagnosis with spiral CT angiography in case of suspected ventral
      perforation following lumbar disc surgery.
AB  - BACKGROUND: Ventral perforation and vascular lesions are rare but life
      threatening complications in lumbar disc surgery. In some cases, however, it
      remains unclear from the clinical situation whether a laparotomy is necessary to
      save the patient. The goal of this study is to demonstrate the value of spiral CT
      (computed tomography) angiography for emergency vascular diagnosis in two cases.
      METHODS: Spiral CT angiography with an intravenous bolus contrast medium
      injection and reconstruction with images in sagittal, coronal, and oblique planes
      was performed. RESULTS: Spiral CT angiography confirms or excludes a vascular
      lesion, as demonstrated in two case reports. CONCLUSION: In unclear cases when
      ventral perforation in lumbar disc surgery is suspected, the need for emergency
      laparotomy can be confirmed quickly by noninvasive spiral CT angiography.

PMID- 11834266
TI  - Herpes simplex encephalitis: the role of surgical decompression.
AB  - BACKGROUND: The role of acyclovir for the treatment of herpes simplex
      encephalitis has been well documented, but the role of surgical decompression for
      herpes simplex encephalitis has only rarely been mentioned. The authors report
      two cases of herpes simplex encephalitis that involved surgical decompression.
      CASE DESCRIPTION: In the first case, a therapeutic regimen of acyclovir was begun
      on the 11(th) day of the clinical course, and surgical decompression was
      performed because of impending uncal herniation on the 13(th) day. In the second
      case, a therapeutic regimen of acyclovir was begun on the third day of the
      disease's clinical course, and surgical decompression was performed because of
      impending uncal herniation on the 11(th) day. Both patients had good neurological
      outcomes and were seizure-free 12 months after their surgical procedures.
      CONCLUSION: We conclude that, for patients with herpes simplex encephalitis, it
      is important for the clinician to detect deterioration of consciousness because
      of the mass effect caused by the disease-associated inflammatory process as early
      as is possible. Surgical decompression is indicated for impending uncal
      herniation or intolerable increased intracranial pressure. Such surgery can
      contribute to an improved outcome for patients with herpes simplex encephalitis.

PMID- 11834269
TI  - Growth patterns of craniopharyngioma in children: role of the diaphragm sellae
      and its surgical implication.
AB  - BACKGROUND: Most craniopharyngiomas can be classified as either "prechiasmatic"
      or "retrochiasmatic" according to their growth patterns. The purpose of our study
      was to investigate the factors determining these growth patterns. METHODS: The
      radiological, operative, and pathological findings of 25 consecutive cases were
      reviewed. RESULTS: In cases with prechiasmatic growth (n = 14), most tumors were
      easily separated from the undersurface of the third ventricular floor with the
      exception of a small area at the top of the tumor where tumor-glial interfaces
      occurred. Pathological examination of the tough tumor surface demonstrated well
      organized collagen tissue, which is compatible with diaphragm sellae. All tumors
      of this type had intrasellar components, suggesting a subdiaphragmatic origin for
      this tumor type. On the other hand, tumors with retrochiasmatic growth (n = 11)
      demonstrated a prefixed chiasm, and most of the surface excluding areas exposed
      to ventricular cerebrospinal fluid showed tumor-glial interfaces. With the
      exception of three, all tumors of this type lacked intrasellar components, and
      the diaphragm sellae was depressed and free of tumor, suggestive of a
      supradiaphragmatic infundibular origin of the tumor. CONCLUSION: Growth pattern
      is closely correlated to the origin of the tumor, whether it is above or below
      the diaphragm sellae. In craniopharyngiomas with prechiasmatic growth, the major
      portion of the tumor could be resected by traction. These tumors are candidates
      for the transsphenoidal approach if the sphenoid sinus is pneumatized. Tumors
      with retrochiasmatic growth, which are not covered by diaphragm sellae and
      contact brain tissue directly, are easily torn by traction and the tumor-glial
      interface should be carefully dissected under direct vision.

PMID- 11834272
TI  - Late recurrence of pineal germinoma.
AB  - BACKGROUND: Cerebral germinomas and their occasional recurrences can usually be
      cured by irradiation, chemotherapy, or a combination of the two treatment
      modalities. Late recurrences, as in our case, are distinctly rare. CASE
      DESCRIPTION: This patient presented at age 24 with a calcified tumor in the
      pineal area. The radiological diagnosis was germinoma. No tissue diagnosis was
      obtained. Radiation therapy was given, and there was a complete response. The
      patient's symptoms reappeared 13 years later. Imaging studies revealed a lesion
      in the anterior corpus callosum. A germinoma was diagnosed by stereotactic
      biopsy. Because of complications attributed to the initial course of radiation
      therapy, no further radiation was given. Five courses of chemotherapy resulted in
      a partial remission lasting six months. The patient later died because of massive
      tumor progression with intracerebral, intraventricular, cerebellar, and meningeal
      dissemination. CONCLUSIONS: As this case illustrates, exceptional recurrences of
      cerebral germinomas may appear even many years after adequate initial treatment
      with radiation and chemotherapy.

PMID- 11834275
TI  - Primary CNS lymphoma as a cause of Korsakoff syndrome.
AB  - BACKGROUND: Korsakoff syndrome presents with memory dysfunction with retrograde
      amnesia, anterograde amnesia, limited insight into dysfunction, and
      confabulation. The most common etiology of Korsakoff syndrome is thiamine
      deficiency secondary to alcoholism. There are limited case reports of structural
      lesions causing Korsakoff syndrome. CASE DESCRIPTION: A 46-year-old male with a
      long history of alcoholism presented with a history of confusion, amnesia, and
      confabulation with no localizing features on neurological examination. The
      patient showed no clinical change with intravenous thiamine. Computed tomography
      of the brain revealed a heterogenous, enhancing mass lesion centered within the
      third ventricle, with other lesions found throughout cortical and subcortical
      regions. The patient was given dexamethasone i.v. without noticeable clinical
      improvement but with marked radiological improvement with mass reduction.
      Stereotactic biopsy revealed a diagnosis of primary central nervous system (CNS)
      lymphoma. CONCLUSIONS: Most patients presenting with Korsakoff syndrome have
      thiamine deficiency; however, mass lesions can produce an identical clinical
      picture. This is the first case report of a patient with primary CNS lymphoma
      presenting as Korsakoff syndrome.

PMID- 11834277
TI  - Fatal hemorrhage after radiochemotherapy for leptomeningeal dissemination of
      glioma: report of two cases.
AB  - BACKGROUND: Dissemination of malignant gliomas is often observed, but the
      treatment of choice for leptomeningeal dissemination has not been established.
      CASE DESCRIPTIONS: A 55-year-old man suffered fatal hemorrhage 1 day after whole
      brain irradiation (2 Gy) along with intravenous administration of 150 mg of
      nitrosourea (ACNU) for leptomeningeal dissemination of glioblastoma. A 14-year
      old boy suffered hemorrhage after intrathecal administration of 10 mg of
      methotrexate for recurrence of leptomeningeal dissemination of anaplastic
      astrocytoma 4 months after local brain irradiation and ACNU administration, and
      died 19 days later. CONCLUSION: Massive fatal hemorrhage is an unusual but
      possible acute complication after radiochemotherapy for leptomeningeal
      dissemination of gliomas.

PMID- 11834278
TI  - Lymphocytic infundibulo- neurohypophysitis with hypothalamic and optic pathway
      involvement: report of a case and review of the literature.
AB  - BACKGROUND: Lymphocytic adenohypohysitis and lymphocytic infundibulo
      neurohypophysitis are rare auto-immune mediated diseases of the anterior and
      posterior pituitary, respectively. The former usually manifests as insufficiency
      of anterior pituitary hormone secretion, associated in many patients with
      disturbances of vision. The latter presents as diabetes insipidus of central
      origin. They present most commonly in pregnant or postpartum females. There have
      been infrequent reports in females with no association with pregnancy, and in
      males. CASE DESCRIPTION: We present a nulliparous female with central diabetes
      insipidus, pan-hypopituitarism, and severely impaired vision. Magnetic resonance
      imaging demonstrated a large mass involving the hypothalamus, infundibulum, optic
      nerves, chiasm, and tracts. At operation, the optic pathways were found to be
      grossly involved in the inflammatory mass. Histological examination of a biopsy
      demonstrated a nonspecific, mixed inflammatory infiltrate, composed predominantly
      of lymphocytes and plasma cells. She responded dramatically to treatment with
      dexamethasone, with disappearance of the mass on serial imaging studies and
      improvement in vision. In addition, she received hormone replacement therapy.
      CONCLUSION: We present a case of lymphocytic infundibulo-neurohypophysitis unique
      in the degree of optic pathway inflammatory involvement, with a documented
      response to steroids.

PMID- 11834281
TI  - Moyamoya disease in a Hispanic child: a case report.
AB  - BACKGROUND: Moyamoya disease was initially described by Suzuki and Takaku in 1963
      as a radiographic phenomenon relating to the tiny collateral vessels
      characteristic of the disease that resemble a cloud or puff of smoke. The disease
      is rare and initially it was believed that the disease was confined to the
      Japanese population. It consists of occlusive vascular disease at the Circle of
      Willis with a tendency toward multiple ischemic neurological events and small
      strokes. In older populations it can often be associated with further vascular
      degeneration and intracerebral hemorrhage. This paper discusses the diagnosis,
      treatment, and management of moyamoya disease in a Hispanic child. CASE
      DESCRIPTION: The case of a Hispanic child who presented with transient ischemic
      attacks over a period of 1 year is reported. Magnetic resonance imaging (MRI)
      revealed occlusive vascular disease in the posterior Circle of Willis. Digital
      subtraction cerebral angiography showed vascular occlusion at the base of the
      skull with collateral leptomeningeal and posterior circulation contribution in a
      pattern typical of moyamoya disease. Technetium was injected for a SPECT study
      demonstrating less uptake in the left frontal and left parieto-occipital regions.
      The patient underwent a left superficial temporal-to-middle cerebral artery
      anastamosis followed by a right-sided anastamosis in a second operation. The
      patient tolerated the cerebral revascularization and was symptom-free at 6-month
      follow-up. Cerebral angiography demonstrated improved perfusion in both cerebral
      hemispheres postoperatively. CONCLUSION: This article reports the occurrence of
      moyamoya in a Hispanic child. It illustrates the improved perfusion
      postoperatively as seen on digital subtraction cerebral angiography. Direct
      revascularization is felt to be difficult in children and alternatives such as
      encephaloduroarteriosynangiosis have been advocated. Direct revascularization was
      effective in treating moyamoya disease in this instance. Most of the discussion
      of moyamoya disease has been focused on the Japanese and Far East population.
      This report confirms the entity as occurring in a Hispanic individual in the
      United States with no known Japanese ancestry.

PMID- 11834286
TI  - Reduce your risk for a documentation audit.

PMID- 11834287
TI  - How to build a practice.

PMID- 11834291
TI  - Expression of subunits for the cAMP-sensitive 'olfactory' cyclic nucleotide-gated
      ion channel in the cochlea: implications for signal transduction.
AB  - Cyclic nucleotide-gated (CNG) ion channels have been implicated as functioning in
      sensory transduction and in second-messenger modulation of synaptic
      neurotransmitter release. The olfactory, cAMP-sensitive CNG ion channel in vivo
      is considered to comprise the pore-forming CNG2 subunit together with CNG5 and
      CNG4.3 modulatory subunits. The expression of these 'olfactory' CNG subunit
      transcripts in microdissected subfractions of the rat cochlea and hair cell
      libraries has been investigated with RT-PCR. Unmodified transcripts of CNG2 were
      detected in the organ of Corti, lateral wall and spiral ganglion subfractions.
      CNG5 message was found in both the sensory organ of Corti and the non-sensory
      lateral wall subfractions but not in the spiral ganglion subfraction. The CNG5
      sequence obtained for the organ of Corti fraction encompassed 78% of the
      olfactory CNG5 cDNA sequence. CNG5 message has also been detected in an inner
      hair cell cDNA library. In the lateral wall, unmodified CNG5 sequence was
      observed as well as truncated versions of CNG5 transcripts, one of which was also
      found in the rat brain. The truncated versions were characterized by deletions
      that resulted in a shift in reading frame and the premature appearance of a stop
      codon. The 'olfactory' CNG4.3 cDNA was amplified from all three subfractions.
      Within the cochlea, CNG2 immunoreactivity was selectively distributed in a
      pattern similar to that of adenylyl cyclase type I. Immunoreactivity to CNG2 has
      been localized to stereocilia of inner hair cells. CNG5 immunoreactivity was
      associated with stereocilia and lateral plasma membranes of outer hair cells. We
      conclude that transcripts necessary for a functional cAMP-sensitive CNG ion
      channel are present in the cochlea resulting from combinations of CNG2 with CNG5
      and CNG4.3. Further, the localization of CNG2 and CNG5 immunoreactivity to hair
      cell stereocilia suggests a role for cAMP-sensitive CNG channels in hair cell
      signal transduction.

PMID- 11834292
TI  - A dominant negative mutation of neuronal connexin 36 that blocks intercellular
      permeability.
AB  - Rat connexin 36 (Cx36) was mutated by substituting serine for cysteine at residue
      231 (C231S) and the mutant's effect on the subcellular localization of wild-type
      Cx36 and the intercellular permeability that it confers was determined in human
      HeLa and rat PC12 cells. Cells transfected with the mutant or wild-type Cx36 cDNA
      expressed the expected 36 kDa protein and Cx36 immunoreactivity. Co
      immunoprecipitation experiments with monkey COS-7 cells transiently transfected
      with both mutant and wild-type Cx36 cDNAs demonstrated that the mutant protein
      bound to the wild-type. Double immunofluorescence microscopy of stably
      transfected HeLa cells demonstrated that mutant Cx36 blocked the transport of the
      wild-type Cx36 to the cell membrane, primarily by trapping it in the endoplasmic
      reticulum around the nucleus. Coexpression of the mutant Cx36 with the wild-type
      protein abolished the ability of the latter to permit dye transfer in both HeLa
      and PC12 cells. The findings are the first demonstration of a mutation of Cx36
      that inhibits wild-type Cx36 function in mammalian cells.

PMID- 11834293
TI  - Absence of alpha7-containing neuronal nicotinic acetylcholine receptors does not
      prevent nicotine-induced seizures.
AB  - Nicotine is the primary addictive component in tobacco, and at relatively low
      doses it affects cardiovascular responses, locomotor activity, thermoregulation,
      learning, memory, and attention. At higher doses nicotine produces seizures. The
      mechanisms underlying the convulsive effects of nicotine are not known, but
      studies conducted on a number of inbred strains of mice have indicated a positive
      correlation between the number of alpha-bungarotoxin (alpha-BTX) binding sites in
      the hippocampus and the sensitivity to nicotine-induced seizures. Because alpha7
      containing neuronal nicotinic acetylcholine receptors (nAChRs) represent the
      major binding site for alpha-BTX, mice lacking the alpha7 nAChR subunit were
      predicted to be less sensitive to the convulsive effects of nicotine. To test
      this hypothesis, we injected nicotine intraperitoneally in alpha7 mutant mice and
      found that the dose-response curve for nicotine-induced seizures was similar in
      the alpha7 +/+, alpha7 +/- and alpha7 -/- mice. The retained sensitivity to the
      convulsant effects of nicotine could not be explained by the presence of
      cholinergic compensatory mechanisms such as increases in mRNA levels for other
      nAChR subunits, or changes in binding levels or affinity for nicotinic ligands
      such as epibatidine and nicotine. These findings indicate that alpha7 may not be
      necessary for the mechanisms underlying nicotine-induced seizures.

PMID- 11834294
TI  - Localization of mRNAs for subfamily of guanine nucleotide-exchange proteins (GEP)
      for ARFs (ADP-ribosylation factors) in the brain of developing and mature rats
      under normal and postaxotomy conditions.
AB  - ADP-ribosylation factors (ARFs) play important roles in vesicular trafficking and
      cytoskeletal regulation and its activation depends on guanine nucleotide-exchange
      proteins (GEPs). By way of in situ hybridization histochemistry, the localization
      of mRNAs for subfamily members of low-molecular-weight ARF-GEPs in the rat brain
      was studied at embryonic and postnatal stages. In the embryonic brain, the gene
      expression for msec7-1 was distinct in the ventricular zone while that for msec7
      1, -3 and EFA6 in the mantle zone. In early postnatal brain, the expression for
      msec7-1, -2, -3 and EFA6 was seen widely in various loci of the gray matter with
      different intensity, and the expression of msec7-1 and -2 mRNAs was evident in
      the cerebellar external granule cell layer. In the adult brain, the gene
      expression for the four ARF-GEPs decreased more or less in most gray matter and
      the distinct expression was maintained mainly in the hippocampal and dentate
      neuronal layers and cerebellar cortex. The expression of EFA6 mRNA was also
      evident in the molecular layer of the hippocampus and dentate gyrus. No obvious
      gene expression for cytohesin-4 and ARF-GEP100 was detected in the brain at any
      stages of development. The present findings suggest that ARF-GEPs are
      differentially involved in some processes essential to neuronal differentiation
      and maturation in association with ARFs.

PMID- 11834295
TI  - Pharmacological characterization of vanilloid receptor located in the brain.
AB  - Specific [3H]resiniferatoxin (RTX) binding detects the vanilloid receptor type I
      (VR1). In the present study we demonstrate specific, high-affinity, saturable
      [3H]RTX binding in various areas of monkey brain not known to be innervated by
      primary afferent neurons as well as in spinal cord and dorsal root ganglion
      neurons of the same origin. Detailed pharmacological characterization and
      comparison revealed no major difference in binding affinities between the
      peripheral and the central sites as measured by K(d)/K(i) values. In general,
      lower receptor density was measured in selected brain areas than in the
      periphery. Areas with higher receptor density were detected in the locus
      ceruleus, preoptic area, and medial basal hypothalamus of the brain. Both
      capsaicin and the competitive antagonist capsazepine inhibited the specific
      binding of [3H]RTX to membrane preparations of the dorsal horn of the spinal cord
      and dorsal root ganglia with K(i) values of 4.3+/-0.32 microM and 2.7+/-0.33
      microM, respectively. Inhibition was observed in the central areas (hypothalamus)
      with K(i) values of 0.95+/-0.1 microM for capsaicin and 0.86+/-0.11 microM for
      capsazepine. Previous biological and pharmacological evidence suggested that
      vanilloid receptors were present in the brain. Our results demonstrate that the
      pharmacological properties of both the peripheral and central receptor sites
      display appropriate pharmacological similarity to represent the same receptor
      class. The modest differences in ligand affinities for the vanilloid receptor
      expressed in the brain nuclei and the dorsal root ganglion neurons may correspond
      to differences in sequence, modification or associated proteins.

PMID- 11834296
TI  - Dehydroepiandrosterone (DHEA) and its sulfated derivative (DHEAS) regulate
      apoptosis during neurogenesis by triggering the Akt signaling pathway in opposing
      ways.
AB  - Dehydroepiandrosterone (DHEA) can function to protect neural precursors and their
      progeny targeted with toxic insults; however, the molecular mechanisms underlying
      the neuroprotective effects of DHEA are not understood. We cultured neural
      precursors from the embryonic forebrain of rats and examined the effects of DHEA
      and its sulfated derivative (DHEAS) on the activation of the serine-threonine
      protein kinase Akt, which is widely implicated in cell survival signaling. We
      found that DHEA activated Akt in neural precursor culture, in association with a
      decrease in apoptosis. In contrast, DHEAS decreased activated Akt levels and
      increased apoptosis. The effects of DHEA on neural cell survival and activation
      of Akt were not blocked by the steroid hormone antagonists flutamide and
      tamoxifen, but both were blocked by a PI3-K inhibitor, LY294002. These findings
      suggest that during neurogenesis in the developing cortex, DHEA and DHEAS
      regulate the survival of neural precursors and progeny through the Akt signaling
      pathway.

PMID- 11834297
TI  - Single-cell RT-PCR detects shifts in mRNA expression profiles of basal forebrain
      neurons during aging.
AB  - The medial septum and nucleus of the diagonal band (MS/nDB) contain cholinergic
      and GABAergic neuronal populations that have been identified based on
      immunohistochemical staining and/or electrophysiological properties. We explored
      the molecular diversity of MS/nDB neurons using single-cell reverse transcription
      polymerase chain reaction (scRT-PCR) to assess gene expression profiles during
      aging in individual neurons acutely isolated from young (2-4 months) and aged (26
      27 months) F344 rats. Neuronal gene expression profiles were characterized by
      detection of mRNAs for choline acetyltransferase (ChAT, cholinergic) and
      glutamate decarboxylase (GAD67, GABAergic), as well as mRNAs for calcium binding
      proteins (CaBPs) calbindin-D28k, calretinin and parvalbumin. Four major neuronal
      populations were identified: ChAT-positive (ChAT+) cells, GAD-positive (GAD+)
      cells, ChAT+/GAD+ cells and ChAT negative/GAD negative (ChAT-/GAD-) cells. With
      age, the percentage of cells expressing ChAT mRNA decreased from 53% in young to
      40%, and the expression of GAD67 mRNA was reduced from 56 to 35% of the cells
      tested. The percentage of cells with detectable levels of both ChAT and GAD67
      mRNA was reduced from 24% in young to 9% in aged. Concomitantly, the percentage
      of ChAT-/GAD- cells increased from 15 to 34% with age. Of the CaBPs, calretinin
      expression was observed most frequently in this study, and its detection
      decreased from 33 to 22% of the cells with age. Observations concerning the CaBPs
      were confirmed using in situ hybridization. These results suggest a shift in the
      mRNA expression profiles of MS/nDB neuronal populations during aging and
      exemplify the molecular diversity of cholinergic and GABAergic cells.

PMID- 11834298
TI  - Characterization of mouse homolog of brain acyl-CoA hydrolase: molecular cloning
      and neuronal localization.
AB  - Acyl-CoA hydrolase could provide a mechanism via its potency to modulate cellular
      concentrations of acyl-CoAs for the regulation of various cellular events
      including fatty acid metabolism and gene expression. However, only limited
      evidence of this is available. To better understand the physiological role of
      this enzyme, we characterized a mouse brain acyl-CoA hydrolase, mBACH. The cloned
      cDNA for mBACH encoded a 338-amino-acid polypeptide with >95% identity to the
      human and rat homologs, indicating that the BACH gene is highly conserved among
      species. This was supported by the similarity in genomic organization of the BACH
      gene between humans and mice. Bacterially expressed mBACH was highly active
      against long-chain acyl-CoAs with a relatively broad specificity for chain
      length. While palmitoyl-CoA hydrolase activity was widely distributed in mouse
      tissues, it was marked in the brain, consistent with mBACH being almost
      exclusively distributed in this tissue, where >80% of the enzyme activity was
      explained by mBACH present in the cytosol. Immunohistochemistry demonstrated a
      neuronal localization of mBACH in both the central and peripheral nervous
      systems. In neurons, mBACH was distributed throughout the cell body and neurites.
      Although four isoforms except mBACH itself, that may be generated by the
      alternative use of exons of a single mBACH gene, were cloned, their mRNA levels
      in the brain were estimated to be negligible. However, a 50-kDa polypeptide
      besides the major one of 43-kDa seemed to be translated from the mBACH mRNA with
      differential in-frame ATG triplets used as the initiation codon. These findings
      will contribute to the functional analysis of the BACH gene using mice including
      genetic studies.

PMID- 11834300
TI  - Light-potentiation of acoustic startle response (ASR) and monoamine efflux
      related to fearfulness in Fyn-deficient mice.
AB  - Fyn tyrosine kinase deficient mice are known to show increased fearfulness. We
      investigated the fear response of these mice using the light-potentiation of the
      acoustic startle response (ASR) and examined its neurochemical correlates using
      in vivo microdialysis. Female homozygous Fyn-deficient mice showed an enhancement
      of the startle amplitude under a bright light while heterozygotes and wild-types
      did not show such a change. Along with these behavioral findings, the homozygous
      Fyn-deficient mice showed an increase in extracellular serotonin (5-HT) and
      dopamine (DA) in the prefrontal cortex and 5-HT in the hippocampus when they were
      exposed to bright light, while heterozygous and wild-type mice did not show such
      changes. These results suggest that the increased fearfulness of Fyn-deficient
      mice is related to enhanced serotonergic and dopaminergic activity in the
      prefrontal cortex and limbic system.

PMID- 11834299
TI  - Plasticity-driven gene expression in the rat retina.
AB  - Animals exposed to an enriched environment display features of neural plasticity
      such as an increased brain volume, enhanced number of dendritic spines, as well
      as enlarged synapses. Here we report the first description of molecular
      plasticity in the mammalian retina, as revealed by gene expression. A marked
      upregulation of both NGFI-A and Arc, two candidate-plasticity genes, was observed
      in adult rats that had been exposed to an enriched environment for 3 weeks. This
      increase was paralleled by an increase in the expression of the late genes GAP-43
      and Synapsin I, which also indicated changes in retinal connectivity. Our results
      suggest that both NGFI-A and Arc may regulate mechanisms of plasticity that had
      been invoked by heightened complexity of the visual environment.

PMID- 11834301
TI  - Intrathecal high-dose morphine induces spinally-mediated behavioral responses
      through NMDA receptors.
AB  - Previous research has demonstrated that intrathecal i.t. morphine in a dose of
      60.0 nmol into the spinal subarachnoid space of mice can evoke nociceptive
      behavioral responses consisting of a severe hindlimb scratching directed toward
      the flank followed by biting/licking of the hindpaw. The present study was
      undertaken to examine the involvement of spinal N-methyl-D-aspartate (NMDA) and
      opioid receptors on the behavioral responses evoked by high-dose i.t. morphine.
      Pretreatment with naloxone, an opioid receptor antagonist (1.0 and 4.0 mg/kg,
      s.c.), failed to reverse the morphine-evoked behavioral response, suggesting that
      the morphine effect is not mediated through the opioid receptors in the spinal
      cord. The morphine-induced behavior was dose-dependently inhibited by i.t. co
      administration of the competitive NMDA receptor antagonists, D(-)-2-amino-5
      phosphonovaleric acid (D-APV) (6.25-50.0 pmol) and 3-((+)-2-carboxypiperazin-4
      yl)-propyl-1-phosphonic acid (CPP) (3.125-25.0 pmol). The characteristic behavior
      was also reduced by co-administration of (5R,10S)-(+)-5-methyl-10,11-dihydro-5H
      dibenzo[a,d]cycloheptene-5,10-imine maleate (MK-801) (74.1-250 pmol), an NMDA ion
      channel blocker. Ifenprodil, a competitive antagonist of the polyamine
      recognition site of NMDA receptor ion channel complex, produced a dose-related
      inhibitory effect on the behavioral response to i.t. morphine with less potency
      than the competitive and non-competitive antagonists examined. High doses of (+)
      HA-966, a glycine/NMDA antagonist, induced a dose-dependent inhibition of
      morphine-induced response. The effective dose of i.t. 6-cyano-7-nitroquinoxaline
      2,3-dione (CNQX), a non-NMDA receptor antagonist, needed to reduce the morphine
      induced response, was approximately 10-fold greater than that of D-APV. These
      results suggest that spinal NMDA receptors, but not non-NMDA receptors, may be
      largely involved in elicitation of the behavioral episode following i.t.
      injection of morphine in mice.

PMID- 11834302
TI  - Restricted expression of protocadherin 2A in the developing mouse brain.
AB  - Protocadherins are cell-cell adhesion molecules that are thought to be involved
      in neural development. Here, we report the expression pattern of protocadherin 2A
      (Pc2A) in the developing mouse brain as determined by the in situ hybridization
      technique. In the postnatal day 2 brain, various regions expressed Pc2A including
      the cerebellar cortex, ventral posterior thalamic nucleus, dorsal lateral
      geniculate nucleus, hippocampus and cerebellum (Purkinje cells). In particular,
      some ependymal cells that form the lining of the lateral ventricle and the third
      ventricle and floor plate cells lining the fourth ventricle showed prominent
      expression. In the adult brain, strong expression was restricted to the Purkinje
      cells. Expression in other areas of the adult brain was down-regulated to a faint
      level, and only a weak signal was detected in regions such as the retina,
      olfactory bulb, dentate gyrus of the hippocampus, and in some parts of the medial
      eminence. These observations suggest that Pc2A is expressed in various regions of
      the brain in a developmentally regulated manner.

PMID- 11834303
TI  - Acute administration of antipsychotics modulates Homer striatal gene expression
      differentially.
AB  - Typical and atypical antipsychotics, the mainstay of schizophrenia
      pharmacotherapy, have been demonstrated to affect differently neuronal gene
      expression in several preclinical paradigms. Here we report the differential gene
      expression of the glutamatergic post-synaptic density proteins Homer and PSD-95
      in rat forebrain following acute haloperidol or olanzapine treatment. Moreover,
      considering the extensive interactions between dopaminergic and opioidergic
      systems we also measured striatal preproenkephalin mRNA. Male Sprague-Dawley rats
      were treated with haloperidol 1 mg/kg or olanzapine 0.5 mg/kg or vehicle, i.p.
      and sacrificed 3 h after the injection. Homer gene expression was significantly
      increased in caudate putamen and nucleus accumbens of rats treated with
      haloperidol and in the core of accumbens of rats treated with olanzapine. No
      changes were detected for Homer in prefrontal and parietal cortex in any of the
      experimental groups. PSD-95 gene expression was not modulated in our paradigm by
      administration of either typical or atypical antipsychotics. These results (1)
      suggest a differential modulation of Homer by typical and atypical
      antipsychotics; (2) confirm that Homer can be induced as an early gene with
      putative direct effect on neuronal plasticity and (3) demonstrate different
      response to antipsychotics by different classes of postsynaptic density proteins
      at glutamatergic synapses.

PMID- 11834305
TI  - Preliminary analysis of the mouse cerebellum proteome.
AB  - This paper reports on the initial analysis of protein expression in the mouse
      cerebellum with the proteomics approach. Proteins from cerebellar tissue
      homogenates were separated by two-dimensional gel electrophoresis, and the
      proteins were stained with colloidal Coomassie Blue to produce a high-resolution
      map of the cerebellum proteome. Selected proteins from this map were digested
      with trypsin, and the resulting tryptic peptides were analyzed by matrix-assisted
      laser desorption/ionization mass spectrometry and liquid chromatography
      electrospray quadrupole ion trap mass spectrometry. The mass spectrometric data
      were used to identify the proteins through searches of the SWISSPROT protein
      sequence database. To date, 30 prominent proteins with various functional
      characteristics were identified. These data will be used for future studies of
      differential protein expression in mouse models of neurological disorders.

PMID- 11834304
TI  - The aniracetam metabolite 2-pyrrolidinone induces a long-term enhancement in AMPA
      receptor responses via a CaMKII pathway.
AB  - The present study was conducted to assess the effect of aniracetam and its
      metabolites, such as 2-pyrrolidinone, p-anisic acid, and anisamide butyrate, on
      the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors,
      heteromerically formed of GluR1,2 (GluR1 and GluR2), GluR1,3 (GluR1 and GluR3),
      and GluR1,2,3 (GluR1, GluR2, and GluR3), expressed in Xenopus oocytes. 2
      Pyrrolidinone potentiated kainate-evoked currents through GluR1,2,3 channels in a
      bell-shaped dose-dependent manner at concentrations ranged from 1 nM to 300
      microM, with a maximal effect at 100 microM. The potentiation was long-lasting,
      reaching approximately 180% of basal levels 60 min after 5-min treatment with 2
      pyrrolidinone at 100 microM. 2-Pyrrolidinone (100 microM) potentiated GluR1,3
      channel currents as observed in GluR1,2,3, but instead it depressed GluR1,2
      currents. Aniracetam and p-anisic acid potentiated GluR1,2,3 channel currents,
      but to a lesser extent, each about 130 and 103% of basal levels 60 min after
      treatment at 100 microM. In contrast, anisamide butyrate had no potentiating
      effect on the currents. Potentiation of GluR1,2,3 channel currents obtained with
      2-pyrrolidinone was inhibited by KN-93, a selective inhibitor of
      calcium/calmodulin-dependent protein kinase (CaMKII), while it was not affected
      by GF109203X, a selective inhibitor of protein kinase C or H-89, a selective
      inhibitor of cAMP-dependent protein kinase. The results of the present study
      suggest that 2-pyrrolidinone persistently enhances activity of the Ca2+-permeable
      AMPA receptors, GluR1,3 and GluR1,2,3, by interacting with CaMKII.

PMID- 11834306
TI  - De novo expression of calretinin in trimethyltin-induced degeneration of
      developing rat hippocampus.
AB  - In the model of trimethyltin (TMT)-induced neurodegeneration in developing rat
      hippocampus, calretinin (CR)-immunoreactive neurons are selectively spared and
      even more numerous than in controls. We investigated the possibility of an
      additional synthesis of CR using RT-PCR. The amount of CR mRNA increased
      significantly after TMT treatment. CR mRNA production after TMT treatment could
      hypothetically be regarded as a compensatory phenomenon in developing rats.

PMID- 11834307
TI  - EB1 identifies sites of microtubule polymerisation during neurite development.
AB  - EB1 is a microtubule associated protein which interacts with the APC tumour
      suppressor protein and components of the cytoplasmic dynein/dynactin complex. EB1
      is also a specific marker of growing microtubule tips. Here we demonstrate that
      EB1 protein levels are increased during axon but not dendrite formation in
      differentiated N2A neuroblastoma cells, and that EB1 localises to microtubule
      tips throughout extending neurites in these cells. In N2A axons, analysis of the
      ratio of EB1/beta-tubulin fluorescence demonstrated that the distal tip region
      contained the highest proportion of polymerising microtubules. Time-lapse
      confocal imaging of an EB1-GFP fusion protein in transfected N2A cells directly
      revealed the dynamics of microtubule extension in neurites, and demonstrated the
      existence of unusual, discrete knots of microtubule polymerisation at the
      periphery of non-process bearing cells which may represent an early event in
      neurite outgrowth. We conclude that EB1 localisation can be used to identify and
      analyse sites of microtubule polymerisation at a high resolution during neurite
      development, a process to which it may contribute.

PMID- 11834308
TI  - Localization of the tandem pore domain K+ channel KCNK5 (TASK-2) in the rat
      central nervous system.
AB  - Tandem pore domain K+ channels (2P K+ channels) are responsible for background K+
      currents. 2P K+ channels are the most numerous encoded K+ channels in the
      Caenorhabditis elegans and Drosophila melanogaster genomes and to date 14 human
      2P K+ channels have been identified. The 2P K+ channel TASK-2 (also named KCNK5)
      is sensitive to changes in extracellular pH, inhibited by local anesthetics and
      activated by volatile anesthetics. While TASK-1 has been shown to be involved in
      controlling neuronal cell excitability, much less is known about the cellular
      expression and function of TASK-2, originally cloned from human kidney. Previous
      studies demonstrated TASK-2 mRNA expression in high abundance in human kidney,
      liver, and pancreas, but only low expression in mouse brain or even absent
      expression in human brain was reported. In this study we have used
      immunohistochemical methods to localize TASK-2 at the cellular level in the rat
      central nervous system. TASK-2 immunoreactivity is prominently found in the rat
      hippocampal formation with the strongest staining observed in the pyramidal cell
      layer and in the dentate gyrus, and the Purkinje and granule cells of cerebellum.
      Additional immunofluorescence studies in cultured cerebellar granule cells
      demonstrate TASK-2 localization to the neuronal soma and to the proximal regions
      of neurites of cerebellar granule cells. The superficial layers of spinal cord
      and small-diameter neurons of dorsal root ganglia also showed strong TASK-2
      immunoreactivity. These results suggest a possible involvement of TASK-2 in
      central mechanisms for controlling cell excitability and in peripheral signal
      transduction.

PMID- 11834309
TI  - Foreperiod duration and motor preparation during childhood.
AB  - The purpose of this experiment was to examine the development of motor
      preparation across three groups of children aged 6, 8 and 10 years old. The
      foreperiod duration (500, 1000, 2000 and 4000 ms) and the motor preparation
      conditions were manipulated using a priming procedure. Two type of primes were
      provided: (1), a prime carrying no advanced information (neutral condition); and
      (2), a prime giving advanced information on the nature of the motor response to
      execute, allowing the participant to prepare for it (selective condition).
      Reaction time and response errors were analyzed. Results showed that under both
      conditions, the optimal motor preparation was reached within the same time frame
      which decreased as age increased. As to the optimal alertness level (neutral
      preparation), it is maintained longer as age increases, whereas the optimal motor
      programming level (selective preparation) is reached only for specific foreperiod
      duration.

PMID- 11834311
TI  - Association of attention deficit hyperactivity disorder-related psychopathology
      and personality traits with the serotonin transporter promoter region
      polymorphism.
AB  - The role of the genetic polymorphism within the promoter region of the serotonin
      transporter (5-HTT) gene is under discussion as a modulator for personality
      traits and a risk factor for several mental disorders including attention deficit
      hyperactivity disorder (ADHD). Here we report a significant association of this
      polymorphism with scores on the Wender Utah Rating Scale, which was used for the
      assessment of a history of ADHD-associated symptoms, indicating a higher
      frequency of the long variant allele in individuals with high scores. We found no
      association between the 5-HTT polymorphism and personality traits according to
      the Eysenck Impulsivity Questionnaire and the Freiburg Personality Inventory,
      respectively, except a significant association with social orientation. Thus, our
      study supports the recently reported finding of an association of the 5-HTT
      polymorphism with ADHD. However, since a dimensional assessment of ADHD-related
      symptomatology was used in our study instead of a diagnostic approach, we are now
      on the way in performing further studies regarding diagnostic discrimination and
      comorbidity.

PMID- 11834310
TI  - Constitutive and inducible nitric oxide synthase activities after spinal cord
      contusion in rats.
AB  - Nitric oxide (NO) plays a role in the secondary damage after spinal cord (SC)
      injury. NO is produced by the activity of two classes of enzymes: calcium
      dependent constitutive nitric oxide synthase (NOS) and calcium-independent
      inducible NOS. To determine the time course of both NOS activities after SC
      injury, 50 Wistar rats were submitted to severe SC contusion. NOS activities were
      assayed at the site of SC injury at several times after lesion. Results showed a
      significant increase of 138 and 96% in the constitutive NOS activity at 4 and 8 h
      after the lesion, respectively, as compared to sham-operated rats. iNOS activity
      was increased 72 h after lesion by 103% (P<0.05). In conclusion, both isoforms of
      NOS increase their activity at different time periods after SC injury.

PMID- 11834312
TI  - Increases in the concentration of brain derived neurotrophic factor in the lumbar
      spinal dorsal horn are associated with pain behavior following chronic
      constriction injury in rats.
AB  - Animals exhibiting thermal hyperalgesia as a sign of neuropathic pain 7 days
      after loose ligation of the sciatic nerve exhibited a significant increase in the
      concentration of brain derived neurotrophic factor (BDNF) in their lumbar spinal
      dorsal horn. In contrast, following the disappearance of thermal hyperalgesia 28
      days after loose ligation of the sciatic nerve, there were no differences in BDNF
      levels between control animals and those with sciatic ligations. These data
      suggest a close association in the timeline of the development and disappearance
      of behavioral signs of neuropathic pain with changes in BDNF levels in the lumbar
      spinal dorsal horn, and lend further support to the notion that plasticity in the
      processing of sensory information in the spinal dorsal horn may contribute to the
      development of persistent pain.

PMID- 11834313
TI  - Decrease of the electroacupuncture-induced analgesic effects in nuclear factor
      kappa B1 knockout mice.
AB  - To investigate the involvement of nuclear factor kappa B1 (NF-kappaB1; p50/p105)
      in electroacupuncture (EA)-induced analgesia, 2 and 100 Hz EA stimulations were
      applied at acupoint ST36 (Zusanli) in NF-kappaB1 knockout mice. EA was performed
      for 30 min and tail-flick latencies (TFLs) were evaluated every 15 min for 1 h.
      Wild-type mice displayed a 63.3% increase in TFLs compared to baseline after 2 Hz
      EA, whereas NF-kappaB1+/- mice exhibited a 41.8% increase and NF-kappaB1-/- mice
      showed only a 3.9% increase of TFLs. The TFLs of 100 Hz EA showed similar trends:
      a 72.6% increase of TFLs in wild-type, a 38.6% increase in NF-kappaB1+/- and a
      9.3% increase in NF-kappaB1-/- mice. The present findings suggest that NF-kappaB1
      may play a crucial role in both low and high frequency EA-induced analgesic
      effects.

PMID- 11834314
TI  - Status epilepticus leads to the degradation of the endogenous inhibitor of
      caspase-activated DNase in rats.
AB  - Specific biochemical hallmarks of apoptosis, namely internucleosomal DNA
      fragmentation and caspase-3 activation, appear in the aftermath of status
      epilepticus (SE). This led us to hypothesize that caspase-activated DNase (CAD)
      is involved in DNA fragmentation and apoptotic neuronal cell death following SE.
      The present study aimed to determine whether SE is associated with an activation
      of CAD, as reflected in the degradation of the CAD inhibitor, ICAD. SE was
      induced in adult male Sprague-Dawley rats by kainic acid (12 mg/kg i.p.) and
      seizures were terminated with diazepam after 2 h. At 24, 48, or 72 h after SE
      termination, protein levels of CAD and ICAD were measured by Western blotting
      (after sodium dodecyl sulfate-polyacrylamide gel electrophoresis) using specific
      antibodies. At 48 and 72 h after SE termination, ICAD protein levels
      significantly decreased (by more than 60%) in rhinal cortex and hippocampus as
      compared with those in the same tissue from animals not experiencing SE. No
      changes were detected in total CAD protein levels at any time point, resulting in
      an increase in the ratio of CAD to its inhibitor. The loss of ICAD following SE
      is indicative of a disinhibition of CAD, leading to DNA fragmentation. Consistent
      with this, we observed that the decrease in ICAD between 24 and 48 h was
      accompanied by a marked increase in DNA fragmentation. Our results support the
      proposal that CAD participates in caspase-3-mediated internucleosomal DNA
      fragmentation in the aftermath of SE.

PMID- 11834316
TI  - Acupuncture enhances cell proliferation in dentate gyrus of maternally-separated
      rats.
AB  - Maternal separation in early life can increase vulnerability to neuropsychiatric
      disorders over the lifespan. To investigate the effect of acupuncture on cell
      proliferation in the dentate gyrus (DG), 5-bromo-2'-deoxyuridine (BrdU)
      immunohistochemistry was performed in maternally-separated rat pups. Maternal
      separation, for 7 days from postnatal day 14, induced a significant decrease of
      BrdU-immunoreactive cells in DG, while acupuncture treatment at acupoint Shenmen
      (HT7), at the end of the transverse crease of the ulnar wrist, resulted in the
      significant increase in the number of BrdU-positive cells in DG. However,
      acupuncture at acupoint ST36, near the knee joint, produced no increase in the
      number of BrdU-positive cells. These findings indicate that acupuncture at
      acupoint HT7 appears to stimulate cell proliferation, and we suggested that
      acupuncture may be useful in the treatment of diseases related to maternal
      separation.

PMID- 11834315
TI  - Characterization of histamine H(2)-like receptors in duck cerebral cortical
      membranes by [(3)H]tiotidine binding.
AB  - A selective (according to mammalian criteria) histamine (HA) H(2)-receptor
      radioligand [(3)H]tiotidine ([(3)H]TIOT) was used to characterize HA receptors in
      duck cerebral cortex by an in vitro binding technique. The specific binding of
      [(3)H]TIOT to duck cerebral cortical membranes was found to be rapid, stable,
      saturable, reversible, and of high affinity. Saturation analysis resulted in a
      linear Scatchard plot suggesting binding to a single class of receptor binding
      sites with high affinity (K(d)=19.5 nM) and high capacity (B(max)=356 fmol/mg
      protein). Competition studies showed the following relative rank order of potency
      of various HA receptor ligands to inhibit the [(3)H]TIOT binding: antagonists,
      tiotidine>>ranitidine=zolantidine>or=cimetidine>>mepyramine>thioperamide;
      agonists, HA>or=4-methylHA>2-methylHA>dimaprit>>R(alpha)-methylHA. The biphasic
      nature of the displacement curve for HA and the effect of 5'
      guanylimidodiphosphate indicate the coupling of the studied receptor to G
      protein. It is suggested that HA receptors in the duck cerebral cortex labelled
      with [(3)H]TIOT represent either avian-specific H(2)-like HA receptors or a novel
      subtype of HA receptors, coupled to a signalling pathway other than the adenylyl
      cyclase/cyclic adenosine monophosphate one.

PMID- 11834318
TI  - Influence of affective and cognitive judgments on autonomic parameters during
      inhalation of pleasant and unpleasant odors in humans.
AB  - Hedonic tone is so salient in odor perception that several authors have used
      odors to induce affective states. Various studies have shown that the
      electrophysiological and psychophysiological response patterns induced by
      olfactory stimuli are different for pleasant and unpleasant odors, and that these
      types of odor activate brain structures differentially. These results suggest
      that odors are first categorized according to pleasantness. The objective of the
      present work was to study the possible existence of an involuntary affective
      categorization in olfaction. Given that certain variations in the autonomic
      system, such as skin conductance amplitude and heart rate, are not under the
      voluntary control of human subjects, we used such psychophysiological methods for
      this investigation. Our results indicate that unpleasant odors provoke heart-rate
      acceleration during both a smelling task (control condition: a task in which
      subjects had only to inhale odors) and a pleasantness judgment, but not during a
      familiarity judgment. These results suggest that subjects involuntarily
      categorize odors by their pleasantness.

PMID- 11834317
TI  - Ovarian hormone effects on 5-hydroxytryptamine(2A) and 5-hydroxytryptamine(2C)
      receptor mRNA expression in the ventral hippocampus and frontal cortex of female
      rats.
AB  - Alterations in female gonadal hormones are associated with anxiety and mood
      changes. The aim of the present study was to determine influences of chronic
      gonadal hormone supplementation on 5-HT(2A) and 5-HT(2C) receptor mRNA levels in
      the ventral hippocampus and the frontal cerebral cortex. Ovariectomized adult
      female Sprague-Dawley rats (n=37) received implantation of subcutaneous pellets
      containing different dosages of 17beta-estradiol alone or in combination with
      progesterone, or placebo pellets, for 2 weeks. Serotonin receptor mRNA levels
      were analyzed by in situ hybridization in the ventral hippocampus and 5-HT(2A)
      receptor mRNA also in the frontal cortex. Estradiol treatment in combination with
      low-dose progesterone increased 5-HT(2A) receptor mRNA by 43% in the CA2 region
      of the ventral hippocampus, while estradiol combined with high-dose progesterone
      increased the expression of this gene by 84% in ventral CA1. 5-HT(2A) mRNA
      expression in the frontal cortex was not influenced by hormone manipulation. 5
      HT(2C) receptor gene expression was in the ventral hippocampus decreased in the
      CA2, ventral CA1 and the subiculum subregions by high-dose estradiol treatment (8
      20% decreases). Effects on mood by gonadal hormones can be mediated, at least
      partly, through influences on 5-HT(2A) and 5-HT(2C) receptor expression.

PMID- 11834319
TI  - Anatomical and electrophysiological analysis of the trigeminal nerve in a teleost
      fish, Oncorhynchus mykiss.
AB  - The trigeminal nerve in the rainbow trout, Oncorhynchus mykiss, was examined for
      the presence of A-delta and C fibres. Sections of the three branches of the
      trigeminal nerve were found to comprise a range of fibre types including A-delta
      and C fibres. The size range of the cell bodies of the trigeminal ganglion
      reflected the fibre range since they correlated with the size range of axons in
      the nerve branches. Electrophysiological recordings of evoked activity from the
      ganglion confirmed the presence of these fibre types and the proportion of these
      mirrored the proportion of fibre types in the anatomical analyses. A-beta fibres
      were most common followed by A-delta fibres, then A-alpha fibres with C fibres
      being the fewest fibre type found. In higher vertebrates, A-delta and C fibres in
      the trigeminal nerve convey both somatosensory and nociceptive information to the
      brain. The evolutionary significance of these results is discussed as well as the
      potential for nociceptive capability in a lower vertebrate.

PMID- 11834320
TI  - Absence of center of mass control for leg abduction in long-term weightlessness
      in humans.
AB  - The present investigation describes for the first time leg lateral abduction
      performance during long-term microgravity exposure. Two astronauts took part in
      the experiments, starting 2 weeks into the mission and lasting for 5 months.
      Results on joint angles kinematics confirm previous investigations on parabolic
      flights, showing good task fulfillment for both subjects. Special interest was
      focused on whole body center of mass (CM) positioning. As in short-term
      microgravity, no initial CM lateral shift toward the 'supporting' leg was
      observed. In contrast with short-term microgravity and ground-based experiments,
      no stabilization of the CM medio-lateral position was found but a significant
      shift of CM toward the moving leg was observed. This suggests that the adaptation
      to sustained weightlessness might have led to a microgravity-specific motor
      strategy for leg abduction, which was not focused on CM strategy.

PMID- 11834321
TI  - Age- and gender-related changes in the cochlear sympathetic system of the rat.
AB  - The sympathetic innervation projecting to the cochlea plays an important role in
      the auditory function, there is, however, no information about whether it is
      altered with advancing age. High performance liquid chromatography coupled to
      electrochemical detection was used to quantify both basal and noise-induced
      concentrations of norepinephrine (NE) in the rat cochlea. The cochlear
      concentration of NE was found to be independent of age in adult (3-12 months old)
      and aged (19 and 24 months old) males and the adult females. However, the
      concentrations of NE increased in aged females with respect to the younger ones,
      which suggests an increase in NE synthesis and a reduced NE release. Thus, a
      prominent gender effect emerged from this study, since the NE cochlear
      concentration was lower in adult females than in males, but tended to be the same
      level in aged animals. These modifications could be related to dramatic hormonal
      changes occurring in females with advancing age.

PMID- 11834322
TI  - The times they are a'changin.

PMID- 11834323
TI  - Microvascular changes in large flame burn wound in sheep.
AB  - Advances in local wound management with early excisional therapy have decreased
      morbidity and mortality of massive third-degree burn patients. Although blood
      redistribution within burned tissue is of clinical interest, few studies have
      longitudinally determined the regional blood flow of various layers of the burn
      wound. We used a conscious ovine model in which animals were subjected to 40%
      third degree burn. Burned tissue was divided into the four layers (i.e. skin,
      panniculus carnosus, adipose tissue, and skeletal muscle), and regional blood
      flow was determined separately, with fluorescent microspheres, while measuring
      systemic hemodynamics and total burned tissue microvascular fluid flux. The
      subburn adipose tissue exhibited a remarkable biphasic alteration in regional
      blood flow, whereas the skin layer showed only decreased blood flow during the
      whole experimental period. The increase in blood flow to the adipose tissue seems
      to be related to a sustained fluid filtrate in the postresuscitation period,
      resulting in edema formation mainly located in the adipose tissue at the
      endpoint.

PMID- 11834324
TI  - Laser Doppler imaging prediction of burn wound outcome in children.
AB  - The ability of laser Doppler imaging (LDI) to evaluate burn depth in children was
      investigated. Fifty-seven patients were prospectively studied over a 10-month
      period. Each patient was clinically assessed, photographed and independently
      scanned between 36 and 72 h of the burn. Patients were reviewed until wound
      healing had occurred within 12 days or skin grafting had been performed. The
      median age was 1 year and 10 months (range 5 months to 15 years and 8 months).
      The median body surface area burnt was 7.0% (range 0.5-30%). In 30 patients, the
      burn did not heal within 12 days, 17 of which were grafted. Clinical examination
      correctly determined 66% of deep partial or full thickness burns between 36 and
      72 h of injury compared to 90% using LDI. The LDI was also more specific;
      correctly diagnosing 96% of superficial partial thickness burns as opposed to 71%
      on clinical examination. Moderate degrees of movement did not appear to limit the
      accuracy of the scan.

PMID- 11834325
TI  - The treatment of Lewisite burns with laser debridement---'lasablation'.
AB  - Lewisite (dichloro (2-chlorovinyl) arsine) was first synthesised in 1918 and its
      potential for use in military confrontations as a vesicant agent has been widely
      recognised. These agents cause blistering skin reactions with resultant full
      thickness burns. Effective treatments to date have been delayed by the lack of
      suitable animal models. Porcine skin has recently been used successfully to model
      the development and natural history of these burn injuries. A large white pig
      model (n=6) was employed to investigate the effectiveness of CO(2) and Erbium-YAG
      lasers (EYL) in laser dermabrasion of established Lewisite burns. Burns underwent
      treatment at 4 days post-exposure and were assessed at 1, 2 and 3 weeks,
      thereafter, for the rate of epithelial healing. The re-epithelialisation rates in
      the laser dermabraded groups were accelerated by a factor of four compared to
      untreated controls by the first week (analysis of vartiance, ANOVA, P=0.006 for
      pulsed CO(2) and P=0.011 for Erbium-YAG). Ablation of the burn eschar was thought
      to accelerate the rate of healing by causing partial debridement. This method has
      been termed 'lasablation' and represents a significant advance in the clinical
      management of this type of injury.

PMID- 11834326
TI  - Comparison of one- and two-dimensional programmes for predicting the state of
      skin burns.
AB  - To understand and accurately predict tissue damage following a burn, bioheat
      transfer based mathematical models of the skin were developed. First,
      mathematical equations with multiple factors to represent the different
      properties of the various layers of the skin were formulated. These equations
      were then numerically solved using finite-difference (1-D) and finite-element (2
      D) analysis. By application of a standard Arrhenius model for damage rate, the
      extent of burn injury was computed from the transient temperature solution. The
      study of the thermal efficacy of cooling treatment was done. Numerical results
      calculated by current 1-D and 2-D models were compared and discussed. Temperature
      contours were found to be consistent in both one- and two-dimensions. The current
      finite element code provided some additional precision to previously published
      models as a mesh independent grid was used to enable more accurate numerical
      prediction of thermal and injury patterns as they developed during the injury
      process. The study of thermal efficacy of postburn therapy showed that postburn
      water-cooling could not effectively reduce the extent of burn. However, low
      temperatures may inhibit the action of inflammatory mediators, and/or, low
      temperatures may depress metabolism or microvascular flow thereby reducing long
      term injury. Therefore numerical data obtained in the current study suggest that
      non-thermal factors must be considered in the calculation of the efficacy of
      postburn cooling therapy. It is equally important to realize that when dealing
      with living tissue, any numerical model can provide only an approximate to
      conditions in actual life.

PMID- 11834327
TI  - Ruthenium red attenuated cardiomyocyte and mitochondrial damage during the early
      stage after severe burn.
AB  - OBJECTIVE: To investigate the effects of ruthenium red on cardiomyocyte and
      mitochondrial damage during the early stage after severe burn. METHODS: Adult
      Wistar rats were randomized into normal control group (control), burn group
      (burns) and ruthenium red-treated group (RR) (n=8). Rats in the burn and RR
      groups were scalded to 30% TBSA III degree, and 30 min later, resuscitated with
      Ringer's solution. Ruthenium red was injected into rats of RR group at a dose of
      2mg kg(-1), and again 3h later. Rats were sacrificed at the 6th hour post-scald,
      myocardial mitochondrial respiratory function and Ca(2+) concentration
      ([Ca(2+)](m)), serum creatine kinase (CK) and lactate dehydrogenase (LDH),
      myocardial ATP, ADP, AMP and lactate contents were determined. RESULTS:
      [Ca(2+)](m) in the RR group was significantly lower than that of the burn group.
      Mitochondrial respiratory control rate (RCR) and ST(3) were higher than those of
      burns, but ST(4) was high compared to the control group. Serum CK and LDH of the
      RR group decreased significantly, and were 65.0 and 45.5% of the burn group,
      myocardial ATP content in the ruthenium red-treated group increased by 100.4% and
      lactate level was decreased by 53.5% compared to the burn group. CONCLUSIONS:
      Ruthenium red attenuated myocyte and mitochondrial damage during the early stage
      after severe burns.

PMID- 11834328
TI  - A prospective study of infections in burn patients.
AB  - In a 3-year prospective study, all infections presenting in the burns unit of a
      university hospital were registered in a specially designed database. Two-hundred
      and thirty adult patients were included. Eighty-three patients had in all 176
      infections, giving an infection rate of 48 per 1000 patient days including both
      nosocomial and community-acquired infections. Thirty-five blood-stream infections
      (BSI) occurred in 22 patients; most common micro-organisms were coagulase
      negative staphylococci and methicillin-sensitive Staphylococcus aureus. The
      device-specific BSI rate was 6 per 1000 central venous catheter days, which is
      low compared to other burn units. The pneumonia rate was 41 per 1000 ventilator
      days. Seventy-two patients had 107 burn wound infections. Antibiotics were given
      to only 50% of the burn patients, including 96% of the patients with infection
      and 26% of those without infection. Most frequently used antimicrobials were
      cloxacillin, penicillin and gentamicin. The antibiotic resistance rates were low,
      and multi-resistant bacteria or fungi were rare. The database can be used to
      evaluate the effects of changes in burn treatment, staffing and design of burn
      units, and antimicrobial resistance development in relation to antibiotic usage.

PMID- 11834329
TI  - Body image of patients with burns sequellae: evaluation through the critical
      incident technique.
AB  - The present investigation is a descriptive study, with a retrospective, ex-post
      facto, design. The objectives of this study were to characterize the body image
      changes in patients with burn sequellae, through the critical incident technique
      and to identify and categorize critical incidents, comparing them to the
      characteristics defined by the Taxonomy of the North American Nursing Diagnoses
      Association (NANDA) for the body image disturbance nursing diagnosis. Thirty-five
      patients were interviewed. Two types of critical incidents were identified:
      'facing the mirror'--the moment the patient looks at himself/herself and notices
      the changes in his/her body, and 'facing other people'--the moment the patient
      becomes aware that he/she calls the attention of others. Associated with the
      perceptions of changes in their bodies, the patients reported feelings of fear
      (19), rebellion (18) and shame (12). They also presented coping mechanisms of
      denial (12), rationalization (7), minimization (7) and repression (2). NANDA's
      body image disturbance diagnosis was identified in all patients.

PMID- 11834330
TI  - Direct quantification of autologous serum albumin leakage after burn injury in
      mice.
AB  - The current technique determining the extent of capillary leakage after injury is
      to measure the leakage of dye-labeled foreign albumin. A recent report, however,
      demonstrated that albumin leakage is dependent upon the type of fluorescent dye
      used for labeling. We chose to develop and test a technique for determining the
      extent of vascular albumin leakage after burn injury without the use of dyes.
      Skin and blood samples were harvested at 3h and 7 days after burn injury in mice.
      Total skin lysates and extracts as well as sera were analyzed for albumin
      leakage. Coomassie staining and Western blot analyses of skin preparations
      followed by the densitometric measurement revealed increased levels of albumin,
      suggesting that the leakage of serum albumin started within 3h after burn injury.
      Instead of employing dye-labeled foreign albumin, the use of SDS-polyacrylamide
      gel electrophoresis of tissue extracts followed by Coomassie staining will allow
      for a simple and direct quantification of autologous albumin leakage due to burn
      as well as other types of injury.

PMID- 11834331
TI  - Sauna-related burns: a review of 154 cases treated in Kuopio University Hospital
      Burn Center 1994-2000.
AB  - Bathing in sauna has been customary for Finnish people for centuries. However,
      there are no actual reviews on sauna-related burns in the literature. This 7-year
      retrospective analyses of 598 burn patients treated in Kuopio University Hospital
      Burn Unit revealed that every fourth burn in our unit was sauna-related, giving a
      total of 154 cases. Most of these burns were minor but 54% required operative
      treatment. A total of 71% of patients were male and 40% of all patients were
      under the influence of alcohol. The incidence of sauna-related burns in Finland
      according to our material is 7/100,000, giving a total of 357 patients annually.
      Hence, there is one sauna-related burn per day requiring hospitalization in
      Finland.

PMID- 11834332
TI  - Impact of duodenal feeding on the oxygen balance of the splanchnic region during
      different phases of severe burn injury.
AB  - Enteral nutrition is recommended in burned patients. Depending on the amount
      administered, enteral feeding causes an increase of intestinal oxygen-demand.
      Since intestinal perfusion is decreased after major burns the aim of this study
      was to evaluate, whether duodenal feeding might be a cofactor for the development
      of a splanchnic O(2)-imbalance. In 15 severely burned patients during duodenal
      feeding starting within 6 h after injury the assessment of the CO(2)-gap between
      arterial and gastric CO(2), as a parameter for the measurement of intestinal O(2)
      balance was performed. Beginning prior to enteral nutrition CO(2)-gap
      measurements were carried out to show when the CO(2)-gap increased above 30 mmHg
      during the whole critical illness phase of the patients. When the CO(2)-gap
      increased above 30 mmHg enteral nutrition was reduced by 50% and the CO(2)-gap
      was measured 1 h later. In none of the patients the CO(2)-gap increased during
      increase of enteral nutrition. In seven patients, the CO(2)-gap increased between
      the 6th and 13th day above 30 mmHg and fell significantly 1 h after reduction of
      enteral nutrition. Contrary to the early postburn phase, enteral feeding might
      have adverse effects on the oxygen balance of the intestine in the later stages
      of the critical illness phase.

PMID- 11834333
TI  - The management of burns in a developing country: an experience from the republic
      of Yemen.
AB  - BACKGROUND: Burns management and mortality rates have improved in even developing
      countries including some Arab states. This paper describes an experience with
      burn victims in the Yemen to draw attention to the victims' plight, the challenge
      posed to bodies, such as the International Society of Burn Injury (ISBI), and,
      the basic required corrective measures. PATIENTS AND METHODS: Between 1996 and
      1999, sponsored surgical teams paid four visits to four Yemen cities. The
      patients presented here are a consecutive series of the plastic surgery
      operations that the teams performed. No literature on burn care in the Yemen
      could be traced. RESULTS: The cities visited were Mokalla, Sayown, Taiz and Aden.
      Of 406 plastic procedures, 139 were for post-burn contracture release and are the
      focus of this paper. The victims were mostly children and the hand (49; 35%) was
      the most common site. Types of operation performed were release and split skin
      grafi, excision and full thickness skin grafi, release and local flap, and,
      multiple Z-plasty. CONCLUSIONS: This experience confirms the believe that, given
      initiative and efficient organization of available resources, developing
      countries such as the Yemen can also achieve better burn management. Solutions
      suggested are determining local health needs; onsite conferences, symposia and
      training programs; local personnel to visit burn centers overseas; burn research
      and prevention activities; and epidemiologic studies.

PMID- 11834334
TI  - Helicopter transportation of burn patients.
AB  - Analysis of 437 consecutive acute burn patients transported to our burn center
      revealed 339 transported by ground and 98 by helicopter. There were 18 air
      transport patients from within a 25-mile-radius, and 80 flown further than 25
      miles. Mean age was the same in all groups (P>0.05). Percent total body surface
      area (TBSA) burned was 8.26% in ground transport patients, significantly less
      than the 20.35% (within 25 miles) and 21.40% (greater than 25 miles) seen in
      helicopter transports (P<0.0001). Three percent of ground transport patients and
      28% of helicopter patients had inhalation injury (P<0.0001). There was no
      difference in incidence of inhalation injury among helicopter groups (28 vs. 29%,
      P=0.8). In patients with coexistent inhalation injury, the mean TBSA burned was
      significantly larger when compared with the TBSA of burns without inhalation
      injury (P<0.001). Air transported groups contained patients whose status was not
      critical based upon lack of inhalation injury and small burn size, and who could
      have been transported by ground. Non clinical factors such as insurance status,
      desire to keep ground ambulances in their community, and competing helicopter
      services reluctant to refuse to transport a patient appears to be factors in
      choosing air ambulance transportation. Regional single helicopter services and
      regional cooperative ground ambulance services should reduce use of helicopter
      transport of burn patients when it is not clinically indicated.

PMID- 11834336
TI  - Treatment of bilateral severe eyelid burns with skin grafts: an odyssey.
AB  - Eyelid burns occur in about 10% of thermal injuries and pose a considerable
      challenge for the reconstructive surgeon. A consensus on a treatment regime has
      not been reached and plastic surgeons are divided on the subject. A case of
      severe bilateral eyelid burns was treated with full- and split-thickness skin
      grafts. The patient was first operated at 2 years post-injury, and a total of 5
      operations in 5 years were necessary to address recurrent ectropion of both upper
      and lower eyelids.

PMID- 11834335
TI  - Characteristics of burn patients transported by ambulance to treatment facilities
      in Akita Prefecture, Japan.
AB  - This study analyzes patient demographics and injury data of 342 patients
      transported by ambulance to emergency facilities in Akita Prefecture, Japan,
      between 1996 and 2000. Significant findings include the following. Fire was the
      most frequent cause of burn injury, and winter was the season with the highest
      incidence (40.6%) of cases. The suicide rate in Akita Prefecture is high, the
      percentage of burn patients due to suicide attempts was 7.9%. The mean time from
      burn injury to hospital arrival was significantly longer for patients who later
      died (44.6 +/- 35.3 min) than for those survived (33.0 +/- 22.5 min). Severely
      burned patients were not always transported directly to a core emergency facility
      and an unacceptable number (5.8%) of patients died at tertiary hospitals. This
      relatively high death rate is attributable to the limited facilities for treating
      burns in the tertiary hospitals and the long distance to core facilities, which
      sometimes precludes transport system for the prefecture will reduce transport
      time to the regional trauma center and thus enable more patients to undergo
      specialized treatment at an earlier injury stage. Additionally, tertiary
      facilities should improve their level of burn care (e.g., creating a burn unit
      and skin bank).

PMID- 11834337
TI  - Occult brain tumour presenting with burns.
AB  - An elderly male patient sustained mixed depth burns of 5% total body surface
      area. The incident was associated with inappropriate behaviour and subsequent
      clinical examination confirmed the presence of confusion and a hemiparesis. A CT
      scan revealed an intracranial tumour. Despite early suspicions that tumour
      excision would be delayed, wound healing was achieved quickly following
      tangential burn wound excision and skin grafting, and prompt transfer to a
      neurosurgical unit was expedited. Cases of burns and concomitant intracranial
      tumours with deteriorating neurological signs may present clinicians with a
      dilemma in deciding whether or not to await burn wound healing before carrying
      out tumour excision.

PMID- 11834338
TI  - Abuse of silver-nitrate solution for planing periorbital folds.
AB  - When using a Hollensteinstift to treat periorbital folds a 28-year-old female
      patient perceived a chemical burn of the lower lids and the periorbital regions.
      The initial treatment was frequent washing with soap solution and topical
      panthenol ointment. This unusual case is demonstrated to show the risks of
      improper use of silver-nitrate solution and to discuss therapeutic options.

PMID- 11834339
TI  - Injuries to children caused by burning rice husk.
AB  - A case study of injury to the feet of children from Sri Lanka due to burning husk
      is discussed. The hot husk causes deep burns on the dorsum of the feet and spares
      the plantar surface. The contractures caused by the burns lead to severe
      deformity, and are very resistant to treatment. These burn injuries need to be
      treated early, in specialized centers, to avoid long term complications. Health
      education of the public plays an important role in the prevention of these
      injuries.

PMID- 11834340
TI  - Wood ash: an unusual cause of a chemical burn.
AB  - The case illustrates the dangers of wood ash even though it appears harmless.
      People believe that this folklore medicine remedy provides relief of pain, but it
      is obviously an inappropriate preparation and a risky procedure.

PMID- 11834342
TI  - Acellular allograft dermal matrix: immediate or delayed epidermal coverage?

PMID- 11834343
TI  - Dynamic analysis of beat-to-beat fetal heart rate variability recorded by SQUID
      magnetometer: quantification of sympatho-vagal balance.
AB  - BACKGROUND: Quantitative analysis of fetal heart rate variability (HRV) can be
      used to investigate the neural control mechanisms of fetal cardiac activity.
      However, conventional power spectrum methods do not reveal the full complexity of
      the time-varying sympatho-vagal balance in the fetus. AIM: This study was carried
      out to explore alternative digital signal processing methods of analysing fetal
      HRV in time domain (rather than frequency domain), in line with most types of
      physiological monitoring. METHODS: The beat-to-beat fetal heart rate was obtained
      by Superconducting Quantum Interference Device (SQUID) magnetocardiographic
      recording. These data were filtered within appropriately selected frequency
      bands: high frequency (HF) f>0.2 Hz, low frequency (LF) 0.05<f<0.2 Hz and very
      low frequency (VLF) f<0.05 Hz. To quantify the dynamics of sympathetic
      parasympathetic interaction, the integrated amplitude of the HF curve (within a
      moving 4-s time window) was compared with the LF component. Also, the interaction
      of the VLF component with both HF and LF components was analysed. RESULTS: A high
      degree of correlation was observed between these components for extended periods
      of time, although the presence of a strong correlation was found to depend on the
      fetal behavioural state. It was further observed that the low-frequency
      oscillations lag high-frequency activity by 1-3 s. CONCLUSIONS: We propose a
      numerical parameter, based on the ratio of the LF to HF components of the fetal
      HRV as a quantitative measure of the relative gain of the parasympathetic system.
      Our results show this parameter to decrease with gestational age of the fetus.

PMID- 11834344
TI  - Lung function, arterial pressure and growth in sheep during early postnatal life
      following single and repeated prenatal corticosteroid treatments.
AB  - BACKGROUND: Antenatal corticosteroid therapy is of great benefit to preterm
      infants, owing largely to effects on lung maturation. In sheep, repeated
      betamethasone injections given to the ewe improve lung function following preterm
      birth but also cause intrauterine growth restriction (IUGR). In humans and in
      animal models, IUGR is associated with impaired postnatal lung function. The
      effects on lung function of repeated prenatal betamethasone treatments and
      associated IUGR following term delivery are unknown. AIM AND STUDY DESIGN: To
      determine the effects of antenatal betamethasone treatments on postnatal arterial
      pressure, blood gases, ventilation, pulmonary gas volumes and compliance in
      serial studies of four groups of lambs until 4 weeks of age. SUBJECTS: Treatment
      groups were (1) maternal injections of saline at 104, 111 and 118 days of
      gestation, (2) a single maternal injection of betamethasone (0.5 mg/kg) at 104
      days followed by saline at 111 and 118 days, (3) repeated betamethasone
      injections at 104, 111 and 118 days, or (4) no intervention (term is
      approximately 150 days). RESULTS: Repeated maternal betamethasone injections
      reduced birthweight and resulted in reduced postnatal body weights and arterial
      pressure throughout the first postnatal month. Lung function was not
      deleteriously affected by single or repeated maternal betamethasone treatments:
      blood gases, minute ventilation, lung volumes and compliance were not different
      between groups of lambs. CONCLUSIONS: The absence of alterations in postnatal
      blood gases contrasts with other models of IUGR in sheep and suggests that
      changes in lung structure caused by betamethasone may benefit IUGR neonates born
      at term.

PMID- 11834345
TI  - Rapid-eye-movement sleep in jittery infants.
AB  - BACKGROUND: The pathogenesis of neonatal jitteriness (JT) remains unknown.
      Neonatal JT could be one of the symptoms associated with drug withdrawal syndrome
      due to maternal medication. To study the influence of chemicals and environment
      on brain development in the fetal period, Swaab and Mirmiran proposed "behavioral
      teratology". JT could be one of the targets for this concept. Swaab and Mirmiran
      postulated that rapid-eye-movement sleep (REM sleep) is useful for studying
      behavioral teratology. AIM: We aimed to determine the neurophysiological
      alterations in infants with JT by investigating REM sleep. STUDY DESIGN: Sleep
      records were obtained three times for each of six jittery infants. The mothers of
      three infants had been on medication (either alpha-methyl dopa, reserpine or
      haloperidol) during pregnancy, whereas the mothers of the other three infants
      took no medication during pregnancy. REM sleep parameters (the amount of REM
      sleep against the total sleep time, newly designated indices-tonic inhibition
      index (TII) and phasic inhibition index--, and the incidences of gross movements,
      phasic chin muscle activity (PCMA), and bursts of rapid eye movements) in the six
      jittery infants were compared with those in age-matched controls. RESULTS:
      Regardless of maternal medication, TIIs, which represent the shortening of PCMA
      during REM sleep, were higher in the jittery infants than in the controls. No
      other REM sleep parameters showed constant differences between the patients and
      controls. CONCLUSION: Release of the blockade of dopamine D2 receptors in the
      fetal brain is considered to be critical for the occurrence of neonatal JT with
      elevation of TII. Since the abnormal elevation of TII continued after 6 months of
      age when our patients did not show JT anymore, we have to keep monitoring jittery
      infants from the standpoint of "behavioral teratology".

PMID- 11834346
TI  - Rehospitalization of extremely-low-birth-weight infants in first 2 years of life.
AB  - AIMS: To determine whether (1) chronic lung disease (CLD) is the prime reason for
      extremely-low-birth-weight (ELBW) infant readmission during the first 2 years of
      life, (2) surfactant and other advanced therapies have reduced ELBW infant
      readmissions, (3) home oxygen therapy (HOT) is efficacious for this group. STUDY
      DESIGN: The hospital records of these ELBW infants were reviewed retrospectively.
      Data on age, diagnosis, treatment, and duration of each hospitalization were
      compiled and analyzed for their association to CLD and to readmission for CLD and
      other reasons. SUBJECTS: All 60 surviving infants with a birth body weight of
      less than 1001 g (ELBW) born from January 1993 to February 1998 were followed up
      to 2 years (mean 20.4 +/- 7.4 months) to evaluate their respiratory outcome.
      RESULTS: Forty-two percent of these infants developed CLD. Upon discharge from
      the hospital, 28% (7/25) of the patients were given HOT for a median period of 60
      days. Of the 47 ELBW infants who were studied the entire 2-year period, 72% were
      readmitted. Infants with CLD were readmitted more frequently (p=0.045) and had
      longer hospital stays during the first 2 years of life (p=0.034) than those
      without CLD. Respiratory illness was the main reason for readmission (55%) of
      these ELBW infants. The incidence of readmission due to respiratory tract
      infection was not significantly different in infants with CLD (61%) and infants
      without respiratory complications (44%) (p=0.159). CONCLUSIONS: Infants with CLD
      (whether receiving HOT or not) showed no higher readmission rate due to
      respiratory infection, but the HOT group did have higher morbidity. The premature
      lung itself rather than the presence of CLD, as we would expect, makes ELBW
      infants more prone to readmission for respiratory illness.

PMID- 11834347
TI  - ACC/AHA guidelines for the evaluation and management of chronic heart failure in
      the adult: executive summary.

PMID- 11834348
TI  - Safety and efficacy of atorvastatin in heart transplant recipients.
AB  - BACKGROUND: Pravastatin and simvastatin prolong survival and reduce transplant
      related coronary vasculopathy, although low-density lipoprotein (LDL) lowering
      with these agents is only modest. The objective of this study was to assess the
      safety of moderate dose atorvastatin and its efficacy when prior treatment with
      another statin had failed to lower LDL to < 100 mg/dl. METHODS: Data from 185
      patients were retrospectively evaluated for adverse events, duration of exposure
      (person-days), and the mean atorvastatin dose exposure. Changes in lipid
      parameters, and prednisone and cyclosporine doses were determined. RESULTS: 
      SAFETY: 48 patients received atorvastatin for 24,240 person-days at a mean dose
      exposure of 21 +/- 10 mg. Rhabdomyolysis, myositis, myalgias, and hepatotoxicity
      occurred in 0, 2, 2, and 0 patients, respectively. All events occurred at the 10
      mg dose, within the first 3 months, and were rapidly reversible with atorvastatin
      discontinuation. EFFICACY: Thirty-four patients evaluable for efficacy analyses
      had a pre-atorvastatin LDL of 145 +/- 38 mg/dl on the following statins:
      pravastatin (n = 30, 40 +/- 0mg), fluvastatin (n = 3, 33 +/- 12 mg), simvastatin
      (n = 1, 40 mg). After atorvastatin (21 +/- 9 mg/day) for 133 +/- 67 days, LDL was
      reduced to 97 +/- 24 mg/dl (relative reduction 31 +/- 20%, p < 0.0001). At the
      end of the observation period (418 +/- 229 days, atorvastatin final dose 24 +/-
      14 mg/day), LDL was further decreased to 88 +/- 23 mg (relative reduction 37 +/-
      17%, p < 0.0001). CONCLUSION: Atorvastatin, when used at moderate doses and with
      close biochemical and clinical monitoring, appears to be safe and is effective in
      aggressively lowering LDL in heart transplant recipients when treatment with
      other statins has failed to achieve LDL goals.

PMID- 11834349
TI  - Temporal changes in myocardial endothelial nitric oxide synthase expression
      following human heart transplantation.
AB  - BACKGROUND: The incidence of cardiac allograft vasculopathy increases with time
      after heart transplantation. Allograft vasculopathy is associated with
      endothelial dysfunction and reduced endothelium-dependent nitric oxide-mediated
      vascular effects. In this study, temporal changes in endothelial nitric oxide
      synthase (NOS3) expression in human myocardial biopsies were investigated during
      the first 3 years after heart transplantation. METHODS: In each patient (n = 7),
      the immunohistochemical presence of NOS3 and inducible nitric oxide synthase were
      examined in serial biopsies taken at 1, 4, and 26 weeks and at 1, 2, and 3 years
      after transplantation. RESULTS: Endothelial nitric oxide synthase was present in
      vascular endothelial cells in all biopsies at the time of transplantation. A
      rapid fall within the first months in the number of NOS3-positive biopsies was
      observed, with a possible difference in the rate of disappearance among the
      capillaries, the arterial endothelium, and the venous endothelium. After 2 years,
      very little NOS3 could be detected. Inducible nitric oxide synthase was present
      in vascular smooth muscle cells throughout the study period and did not change.
      CONCLUSION: Endothelial nitric oxide synthase immunoreactivity is gradually lost
      after heart transplantation. These changes may be responsible for the coronary
      endothelial dysfunction often seen after human cardiac transplantation.

PMID- 11834350
TI  - Association of lung perfusion disparity and mortality in patients with cystic
      fibrosis awaiting lung transplantation.
AB  - BACKGROUND: The risk of death for patients with end-stage cystic fibrosis
      awaiting lung transplantation remains high and most patients succumb to
      respiratory failure. This study was conducted to evaluate the usefulness of
      ventilation-perfusion scintillation scans, obtained during the pre-transplant
      period, to identify patterns that predict prognosis while on the waiting list.
      These patterns were compared with other pulmonary physiologic markers of
      ventilation and perfusion obtained from pulmonary function and cardiopulmonary
      exercise tests. METHODS: From November 1990 to January 1999, 46 patients with
      cystic fibrosis were listed for bilateral lung transplantation. Fourteen (30.4%)
      died while waiting for a transplant (Group 1), whereas 32 were transplanted
      successfully or remain alive and waiting (Group 2). Mean arterial blood gas
      values, Brasfield radiograph scores, cardiopulmonary exercise data and the degree
      of scintillation scan abnormalities between lungs were compared for each group.
      RESULTS: Mean survival for Group 1 was 10.2 +/- 1.7 months, and for Group 2 was
      23.5 +/- 3.0 months (p < 0.001). The right upper lung zone was the most severely
      affected segment. The Cox proportional hazards model revealed an increased
      perfusion disparity and resting hypercapnia as the main predictors of death while
      on the transplant list. The Kaplan-Meier analysis indicated greater survival for
      the groups with <30% disparity between lungs on the pre-transplant scintillation
      scans. CONCLUSIONS: The results suggest that severe, unilateral perfusion
      abnormalities seen on scintillation scans in patients with cystic fibrosis are
      associated with an increased risk of dying while on the lung transplant waiting
      list and may be helpful in identifying patients who should be considered for
      early or living-donor transplantation.

PMID- 11834351
TI  - Assessment of survival benefit after lung transplantation by patient diagnosis.
AB  - BACKGROUND: Lung transplantation has become an established procedure for treating
      patients with endstage lung disease, resulting in broadening criteria for
      recipient selection. The survival benefit for some patient groups has yet to be
      established. METHODS: We reviewed 653 patients accepted for lung transplantation
      at our center. Patients were categorized into 6 diagnosis groups: cystic fibrosis
      (174), obstructive lung disease (163), pulmonary fibrosis (100), Eisenmenger's
      syndrome (76), pulmonary hypertension (68), bronchiectasis (51), and other (21).
      Using Cox regression, we estimated the time at which early operative risk of
      death fell below pre-operative risk levels (crossover point) and the point at
      which early high post-operative risk was offset by later low risk (equity point).
      The relative benefits of single lung vs double lung/heart-lung transplantation
      were assessed for patients with obstructive lung disease and pulmonary fibrosis.
      RESULTS: Post-operative risk of death fell below pre-operative risk levels for
      all diagnosis groups, indicating a survival advantage. The equity point was
      achieved for all distinct diagnosis groups (except Eisenmenger's); this survival
      benefit was significant for patients with obstructive lung disease, cystic
      fibrosis, and pulmonary hypertension. Single lung vs double lung/ heart-lung
      comparisons showed no significant difference in survival benefit. CONCLUSION: All
      survival benefit patient groups achieve after lung transplantation, with the
      exception of patients with Eisenmenger's syndrome, who may have prolonged
      survival while listed. Differences in survival benefit between single lung and
      double or heart-lung transplantation are not significant for patients with
      obstructive lung disease or pulmonary fibrosis.

PMID- 11834352
TI  - A novel small animal model of left ventricular tissue engineering.
AB  - BACKGROUND: Complex congenital cardiac anomalies involving ventricular hypoplasia
      require either staged palliative reconstruction, converting the circulatory
      system to a single ventricle based pump, or allogeneic transplantation. Tissue
      engineering offers the potential for complete reconstruction of these defects,
      but is limited by the inability to model myocardial tissue engineering in a small
      animal. Our goal was to develop a small animal model for ventricular tissue
      engineering using rat heterotopic heart transplantation. METHODS: Donor hearts
      were explanted after cardioplegic arrest and the left ventricular volume was
      augmented by the implantation of a biodegradable engineered construct. The heart
      was then transplanted heterotopically into syngeneic recipients creating either a
      volume loaded, functioning left ventricle, or a non-functioning left ventricle.
      Some of the engineered constructs were seeded with multipotent bone marrow
      derived mesenchymal progenitor cells before implantation. Animals were evaluated
      by echocardiography, morphology, histology, and immunohistochemistry after 1
      month. RESULTS: A scaffolding constructed from polytetrafluoroethylene,
      polylactide mesh, and type I and IV collagen hydrogel resulted in minimal
      intracardiac inflammation without aneurysmal dilatation. Successful
      transplantation and differentiation of mesenchymal progenitor cells was
      accomplished using this scaffolding. No ventricular arrhythmias resulted from
      this surgical manipulation and echocardiography revealed both end systolic and
      diastolic volume augmentation with ventricular expansion. CONCLUSION: We have
      developed an in vivo model of ventricular tissue engineering using heterotopic
      heart transplantation. Future work will focus on construction of ventricular
      tissue around pre-fabricated vascular networks in order increase cellular
      engraftment for ventricular reconstruction.

PMID- 11834353
TI  - Up-regulation of Bcl-2 through hyperbaric pressure transfection of TGF-beta1
      ameliorates ischemia-reperfusion injury in rat cardiac allografts.
AB  - BACKGROUND: Oxidative stress after ischemia-reperfusion of cardiac allografts
      leads to activation of cardiomyocytes and production of cytokines. Bcl-2, an
      inhibitor of the apoptotic pathway, also has strong antioxidant properties.
      Ischemia-reperfusion injury after transplantation leads to decreased bcl-2 and
      increased tumor necrosis factor (TNF)-alpha levels. Transforming growth factor
      (TGF)-beta1 is known to attenuate ischemia-reperfusion injury and inhibits
      apoptosis of myofibroblasts. We hypothesize that TGF-beta1, prevents bcl-2
      cleavage and increased TNF-alpha production. METHODS: Rat PVG donor hearts were
      heterotopically transplanted into ACI recipients. Donor hearts were procured and
      assigned to groups: (1) intracoronary TGF-beta1 (200 ng/ml) perfusion and
      pressure at 78 psi for 45 minutes (n = 4); (2) intracoronary TGF-beta1 perfusion
      and incubation for 45 minutes without pressure (n = 4), (3) saline perfusion and
      incubation for 45 minutes without pressure (n = 4). Hearts were procured 4 hours
      after transplantation and analyzed by reverse transcriptase-polymerase chain
      reaction for bcl-2 mRNA expression, ELISA for TNF-alpha, and for myeloperoxidase
      activity (MPO). RESULTS: Bcl-2 decreased in untreated animals (bcl-2:G3PDH ratio
      = 0.85 +/- 0.73 vs 1.16 +/- 0.11, not significant [NS]), whereas TNF-alpha
      increased to 669.99 +/- 127.09 vs 276.84 +/- 73.65 pg/mg total protein in
      controls (p < 0.003). In TGF-beta(1) pressure-treated hearts, bcl-2 was up
      regulated (2.49 +/- 0.6 vs 1.16 +/- 0.11, controls, p < 0.005), whereas TNF-alpha
      was unchanged (396.1 +/- 100.38 vs 276.84 +/- 73.65 pg/mg, NS). Hearts treated
      with TGF-beta1 and pressure showed significant up-regulation of bcl-2 compared
      with hearts treated with TGF-beta1 without pressure (2.49 +/- 0.6 vs 1.17 +/-
      0.6, p < 0.02). MPO showed no differences. CONCLUSIONS: Bcl-2 is down-regulated
      and TNF-alpha up-regulated in this model of ischemia-reperfusion injury.
      Furthermore, TGF-beta1 is linked to this process and ameliorates reperfusion
      injury by up-regulating bcl-2 and inhibiting TNF-alpha. Therapeutic
      overexpression of myocardial TGF-beta1 may be clinically useful to control
      ischemia-reperfusion injury associated with cardiac transplantation.

PMID- 11834354
TI  - Protective effects of inhaled nitric oxide and gabexate mesilate in lung
      reperfusion injury after transplantation from non-heart-beat donors.
AB  - BACKGROUND: The use of lung grafts from non-heart-beat donors (NHBDs) is one way
      of solving the critical donor organ shortage. Inhaled nitric oxide (NO) and
      gabexate mesilate (FOY), a protease inhibitor, can attenuate some types of
      neutrophil-mediated tissue injury. Using an isolated lung ventilation and
      perfusion model, we studied the effects of these agents on reperfusion injury
      following lung transplantation from NHBDs. METHODS: Five groups of minipigs were
      studied. In group 1(n = 6), the lungs were flushed and harvested after cardiac
      arrest, and were reperfused for 2 hours after 2 hours of cold ischemia. In group
      2 (n = 6), the lungs were harvested after 2 hours of in situ warm ischemia,
      followed by 2 hours of cold ischemia and 2 hours of reperfusion. In groups 3 (n =
      7), 4 (n = 7), and 5 (n = 6), the procedure was the same as in group 2, except in
      group 3, NO was inhaled before and after ischemia, in group 4, FOY was given
      intravenously, and in group 5, a combination of inhaled NO and intravenous FOY
      were administered. RESULTS: Compared with group 1, group 2 had higher mean
      pulmonary arterial pressure, vascular resistance, and lower arterial blood oxygen
      tension. Furthermore, these negative effects of warm ischemia were also reflected
      in the contents of bronchoalveolar lavage fluid, tissue myeloperoxidase (MPO)
      activity, histology, and permeability change. Either FOY or NO administration
      (groups 3 or 4) ameliorated the associated injury. A combination of FOY and NO
      use (group5) decreased the parameters of lung reperfusion injury measurement to a
      larger degree than either agent individually. CONCLUSIONS: The inhaled NO and FOY
      can protect NHBD lung grafts at an early reperfusion period. Their use in
      combination has an additive protective effect that might be applied to the
      protection of NHBD grafts from preservation and reperfusion injury.

PMID- 11834355
TI  - An optimal experimental design for the development of preservative heart
      solutions.
AB  - BACKGROUND: The aim of this study was to determine the optimal composition of a
      new medium for long-term hypothermic heart preservation. METHODS: The independent
      effects of 19 compounds were evaluated using an in vitro porcine model. Tissue
      viability was assessed by measuring the reduction of methyltetrazolium salt,
      oxygen consumption and energetic compound levels on myocardial biopsies after 24
      , 48- or 72-hour incubation periods. Screening of several compounds at two
      concentrations was performed to greatly reduce the number of experiments.
      RESULTS: Pyruvate, aspartic acid, chlorpromazine and polyethylene glycol
      displayed protective properties, whereas calcium (2 mmol/liter), nifedipine,
      mannitol, magnesium (16 mmol/liter) and reduced glutathione showed deleterious
      effects. On the basis of these data, the composition of a new preservation
      solution (Group 1, n = 6) was compared with St Thomas solution (Group II, n = 6)
      in an isolated, 24-hour pig heart preservation model. During reperfusion, left
      ventricular developed pressure and coronary blood flow were significantly higher
      (p <.01) in Group I, suggesting better preservation. CONCLUSIONS: Our technique
      allows for rapid and efficient screening of many compounds currently used in the
      composition of preservation solutions for cardiac surgery.

PMID- 11834356
TI  - Risk factors for bronchiolitis obliterans: a systematic review of recent
      publications.
AB  - BACKGROUND: Obliterative bronchiolitis remains the major limitation to long-term
      survival after lung transplantation. A thorough understanding of the factors that
      confer high risk of developing obliterative bronchiolitis or its physiologic
      surrogate bronchiolitis obliterans syndrome is important to help define
      therapeutic strategies. METHODS: We performed a systematic review of studies
      published since the beginning of 1990. The review excluded non-human studies,
      publications before 1990, small (less than 25 patients) studies that were
      predominantly concerned with investigating the pathogenesis of obliterative
      bronchiolitis, studies solely concerned with diagnosis or treatment of
      obliterative bronchiolitis, and overlapping studies from the same center. Onset
      of bronchiolitis obliterans syndrome or obliterative bronchiolitis was the
      outcome of interest. RESULTS: Acute rejection plays an important role in
      obliterative bronchiolitis and bronchiolitis obliterans syndrome onset, and late
      rejection is a significant risk factor. Lymphocytic bronchitis/bronchiolitis is
      also a risk factor, with some evidence that late onset is associated with greater
      risk. The effects of cytomegalovirus, other infectious organisms, and human
      leukocyte antigen matching are less clear and require further confirmation. There
      is little evidence that recipient and donor characteristics play a major role.
      CONCLUSIONS: This systematic review supports the view that obliterative
      bronchiolitis arises from alloimmunologic injury marked by clinically apparent
      acute rejection episodes and that inflammatory conditions, including viral
      infections or ischemic injury, may also play a role. Implications for therapy are
      discussed.

PMID- 11834357
TI  - Mycophenolate mofetil decreases antibody production after cardiac
      transplantation.
AB  - New immunosuppressive drugs are extensively being investigated for their effect
      on T-cell immunity, with far less being known about their effect on the humoral
      immune response. In view of the experimental and clinical evidence that humoral
      immunity contributes to acute and chronic rejection, we investigated post
      transplant production of anti-vimentin and anti-HLA antibodies in 86 patients who
      were part of a worldwide clinical trial for mycophenolate mofetil in cardiac
      transplantation. The results demonstrate that patients taking MMF instead of
      azathioprine generated significantly fewer de novo anti-vimentin antibodies.

PMID- 11834358
TI  - A simplified model for en bloc double lung xenotransplantation from hamster to
      rat.
AB  - We present a simplified model of lung xenotransplantation from hamster to rat
      with a total non-suture technique using 14G cuffs for the main pulmonary artery,
      the trachea and the left atrium. This technique provides a technically easier and
      more reliable model to study xenotransplantation of the lung.

PMID- 11834359
TI  - Successful explantation of a ventricular assist device following fulminant
      influenza type A-associated myocarditis.
AB  - We report a case of fulminant myocarditis associated with refractory ventricular
      fibrillation following influenza A infection. Histologic examination was
      consistent with myocarditis and serology confirmed the viral etiology. The
      patient was supported with biventricular assist devices for 20 days during which
      her refractory ventricular fibrillation resolved spontaneously. This is the first
      documented case of resolution of prolonged ventricular fibrillation while on a
      ventricular assist device. This case suggests those patients with fulminant viral
      myocarditis and refractory ventricular arrhythmias may be supported successfully
      with ventricular assist devices until myocardial recovery takes place.

PMID- 11834360
TI  - Use of a donor heart that had undergone previous cardiac surgery for ASD closure.
AB  - We report the use of a heart from a 19-year-old female donor who had undergone
      open heart surgery for closure of an atrial septal defect at the age of 12. The
      explantation procedure was modified to prevent hemodynamic instability. The
      recipient, a 59-year-old male with increased pulmonary vascular resistance had an
      uneventful recovery after transplantation.

PMID- 11834364
TI  - Functional and comparative genomics of pathogenic bacteria.
AB  - Microarray expression profiling and the development of data-mining tools and new
      statistical instruments affords an unprecedented opportunity for the genome-scale
      study of bacterial pathogenicity. Expression profiles obtained from bacteria
      grown in media simulating host microenvironments yield a portrait of interacting
      metabolic pathways and multistage developmental programs and disclose regulatory
      networks. The analysis of closely related strains and species by microarray-based
      comparative genomics provides a measure of genetic variability within natural
      populations and identifies crucial differences between pathogen and commensal. In
      the near future, the combined use of bacterial and host microarrays to study the
      same infected tissue will reveal the host-pathogen dialogue in a gene-by-gene and
      site- and time-specific manner. This review discusses the use of microarray-based
      expression profiling to identify genes of pathogenic bacteria that are
      differentially regulated in response to host-specific signals. Additionally, the
      review describes the application of microarray methods to disclose differences in
      gene content between taxonomically related strains that vary with respect to
      pathogenic phenotype.

PMID- 11834365
TI  - Genomic analyses of microbial virulence.
AB  - Genomic sequencing of bacterial pathogens is providing an increasing wealth of
      new data. It is, however, still unclear how this information can be used to
      develop new experimental approaches. Here, we describe recent efforts to
      complement existing bacterial genetics with genomic methods for the study of
      pathogenesis.

PMID- 11834366
TI  - Use of signature-tagged mutagenesis in pathogenesis studies.
AB  - From 2000-2001, over 10 studies have been completed, using signature-tagged
      mutagenesis, on a variety of bacterial pathogens. Investigators are examining the
      attenuated strains in additional in vivo, cell culture or in vitro assays to
      further characterize and catalog the mutants. Notable advances included screening
      of the attenuated mutants en masse in other assays, verification that mutant
      strains are defective for growth in specific host tissues, and identification of
      potential live-attenuated vaccine candidates. In addition, researchers are using
      signature-tagged strains to characterize the infection process, which is
      providing snapshots of bottlenecks and quantitative measurements of bacterial
      spread from tissue to tissue. This review focuses on themes emerging from
      signature-tagged mutagenesis studies completed on bacterial pathogens since mid
      2000.

PMID- 11834367
TI  - Function of the Yersinia effector YopJ.
AB  - The Yersinia virulence factor YopJ inhibits the host immune response and induces
      apoptosis by blocking multiple signaling pathways, including the MAPK and
      NFkappaB pathways in the infected cell. YopJ is a cysteine protease that cleaves
      a reversible post-translational modification in the form of ubiquitin or a
      ubiquitin-like protein. Homologues of YopJ are expressed in animal and plant
      pathogens, as well as a plant symbiont, suggesting a universal mechanism of
      regulating or modulating a variety of signaling pathways. The ability of YopJ to
      block the innate immune response, its activity as a ubiquitin-like protein
      protease and its activity with respect to mammalian signalling pathways are
      discussed in this review.

PMID- 11834368
TI  - Plant disease resistance triggered by pathogen-derived molecules: refined models
      of specific recognition.
AB  - Plant disease resistance is often determined by complementary pairs of resistance
      genes (from the plant) and avirulence genes (from the invading pathogen). This
      gene-for-gene interaction has generally been interpreted as a receptor-ligand
      model in which the avirulence protein binds to the corresponding resistance
      protein, which in turn initiates plant defense. Recent studies indicate that co
      localization of avirulence and resistance proteins is essential for their
      function. However, there is also accumulating evidence that resistance proteins
      are not the primary receptor for the avirulence protein. We review advances in
      our understanding of gene-for-gene resistance and examine validity of the
      receptor-ligand model and other proposed models in the context of the most recent
      findings.

PMID- 11834369
TI  - Acid tolerance of gastrointestinal pathogens.
AB  - The ability of pathogenic bacteria to survive in the face of host defense systems
      is intimately linked to virulence. This is exemplified by gastrointestinal
      pathogens that must survive exposure to extreme acid conditions within the
      stomach and organic acid conditions within the small intestine. These organisms
      have evolved complex systems to respond to acid stress, and recent work has
      revealed new genetic components involved in survival and virulence. Here, we
      review recent work on four gastrointestinal pathogens, focusing on studies that
      reveal both acid-inducible resistance systems and inherent (basal state) acid
      resistance systems.

PMID- 11834370
TI  - A phagosome of one's own: a microbial guide to life in the macrophage.
AB  - Macrophages protect their host by engulfing foreign bodies within phagosomes that
      rapidly develop into microbicidal organelles. Numerous pathogens, such as species
      of Toxoplasma, Leishmania, Mycobacterium, Salmonella and Legionella, thrive in
      human macrophages, sometimes with disastrous effects. Defining the survival
      tactics of intracellular parasites is one approach to understanding macrophage
      function. Here, we briefly review phagosome maturation, then discuss how
      particular microbes may target particular host factors to short-circuit membrane
      traffic in macrophages. Recent studies support a new paradigm in which pathogens
      evade lysosomal degradation by entering macrophages within specialized lipid
      microdomains of the plasma membrane.

PMID- 11834371
TI  - Interactions between bacterial CpG-DNA and TLR9 bridge innate and adaptive
      immunity.
AB  - The astounding adjuvanticity and Th1-polarizing immunobiology of bacterial CpG
      DNA and mimicking CpG-oligonucleotides continue to mirror promising therapeutic
      potential. The past year has witnessed some particularly impressive progress in
      knowledge of its molecular mode of action. Accordingly, CpG-DNA acts as a
      "pathogen-associated" molecular pattern that is recognized by TLR9 expressed, in
      particular, by dendritic cells. Interactions between CpG-DNA and TLR9 rapidly
      activate antigen-presenting dendritic cells through the ancient Toll/IL-1
      receptor signaling pathway to upregulate co-stimulatory molecules and to produce
      Th1-polarizing cytokines, such as interleukin-12 and interleukin-18. Thus,
      interactions between CpG-DNA and TLR9 effectively bridge innate and acquired
      immunity.

PMID- 11834372
TI  - Toll-like receptors: mammalian "taste receptors" for a smorgasbord of microbial
      invaders.
AB  - In Drosophila, the Toll family of proteins is responsible for the recognition of
      bacteria and fungi. In mammals, Toll-like receptors (TLRs) are able to recognize
      and respond to microbial pathogens. Recent findings have defined the relationship
      between many TLRs and their microbial ligands, as well as the effect of TLR
      ligation on host defense. These findings have also provided a framework for
      determining how TLRs may by used to therapeutically modulate immune responses to
      infection.

PMID- 11834373
TI  - Nods: a family of cytosolic proteins that regulate the host response to
      pathogens.
AB  - Genetic variation in Nod2 is associated with susceptibility to Crohn's disease.
      Nod2 and its homologue, Nod1, are members of a growing family of cytosolic
      factors related to the apoptosis regulator Apaf-1 and a class of plant disease
      resistance proteins. Nod1 and Nod2 confer responsiveness to lipopolysaccharides
      and interact with RICK, a mediator of NF-kappaB activation. Nod1 and Nod2 and
      related Nods appear to regulate the host response to pathogens, a process that
      may be faulty in certain inflammatory diseases. Recent studies that suggest that
      Nods may be involved in the recognition of pathogen components in the cytosol of
      mammalian cells are reviewed.

PMID- 11834374
TI  - CFTR mutations and host susceptibility to Pseudomonas aeruginosa lung infection.
AB  - The susceptibility of cystic fibrosis patients to bacterial pathogens is
      associated with deficient airway antimicrobial peptide activity, and airway
      surface-liquid dehydration with decreased transport velocity and hypersecretion
      of mucus. Susceptibility to Pseudomonas aeruginosa infection has been linked to
      the role of the cystic fibrosis transmembrane conductance regulator protein as a
      receptor for P. aeruginosa. Binding of P. aeruginosa coordinates lung clearance
      as part of innate immunity. The function of CFTR in innate immunity to P.
      aeruginosa infection is multifactorial, with one key component being a specific
      ligand-receptor interaction between the protein and the microbe.

PMID- 11834375
TI  - T cell responses to Chlamydia trachomatis.
AB  - Chlamydia trachomatis is the most common cause of bacterial sexually transmitted
      disease in the United States, as well as the leading cause of preventable
      blindness worldwide. Immunity to C. trachomatis requires a variety of cell types,
      each employing an array of effector functions. Recent work has demonstrated that
      both CD4+ and CD8+ T lymphocytes play a major role in protective immunity to C.
      trachomatis, predominantly through their secretion of interferon-gamma. This
      review describes the generation of acquired immunity to C. trachomatis and
      focuses on how T cells contribute to both protection and immunopathology.

PMID- 11834376
TI  - Role of T cells in abscess formation.
AB  - A series of recent studies have shed new light on the strategy used by certain
      bacterial pathogens to induce a classic infectious process: abscess formation.
      This work describes how zwitterionic polysaccharides on the surface of these
      organisms interact with the host immune system in general, and with T cells in
      particular, to coordinate this pathobiologic response.

PMID- 11834377
TI  - Caenorhabditis elegans as a host for the study of host-pathogen interactions.
AB  - Recently, pathogenicity models that involve the killing of the genetically
      tractable nematode Caenorhabditis elegans by human pathogens have been developed.
      From the perspective of the pathogen, the advantage of these models is that
      thousands of mutagenized bacterial clones can be individually screened for
      avirulent mutants on separate petri plates seeded with C. elegans. The advantages
      of using C. elegans to study host responses to pathogen attack are the extensive
      genetic and genomic resources available and the relative ease of identifying C.
      elegans mutants that exhibit altered susceptibility to pathogen attack. The use
      of Caenorhabditis elegans as the host for a variety of human pathogens is
      discussed.

PMID- 11834380
TI  - Treatment of clinical stage I germ cell tumors.

PMID- 11834379
TI  - Immunity to intracellular pathogens as a complex genetic trait.
AB  - Although the role of host heredity in susceptibility to infectious diseases is
      significant, the genetic control of immunity to infection remains poorly
      understood. Advances in experimental and epidemiological analyses of complex
      genetic traits have led to the discoveries of novel genetic determinants of host
      resistance. New loci that control susceptibility to a number of intracellular
      pathogens have been identified using mouse models of infectious diseases. The
      contributions of individual loci, however, vary in quantitative and qualitative
      manner, depending on mechanisms of pathogen virulence and genetic background of
      the host. In this review, we discuss how genetic analysis of host resistance
      contributes to further understanding of host immunity and pathogenesis of
      intracellular infections.

PMID- 11834378
TI  - How Drosophila combats microbial infection: a model to study innate immunity and
      host-pathogen interactions.
AB  - During the past year, dramatic progress has been achieved in our understanding of
      Drosophila immune reactions. The completion of the Drosophila genome sequencing
      project, microarray analysis and the use of genetic screens have led to the
      identification of several new genes required to combat microbial infection,
      filling in some important gaps in the understanding of innate immunity. At the
      same time, this insect was used as a model for the study of host-pathogen
      interactions. The recent major advances on the mechanisms by which this insect
      defends itself against intrusion of pathogens are discussed in this review.

PMID- 11834381
TI  - Classic bladder exstrophy in a nonhuman primate: a comparative analysis.
AB  - OBJECTIVES: To describe the pelvic floor musculature and bony pelvic anatomy in a
      case of naturally occurring classic bladder exstrophy in a rhesus monkey, the
      first reported case in the animal population since 1832, and compare the results
      to exstrophy seen in human newborns. METHODS: A 7-day-old male rhesus monkey with
      classic bladder exstrophy was examined by a pediatric urologist and primate
      veterinarian before being killed. A multidetector row computed tomography study
      with three-dimensional reconstruction was obtained, and a comparison computed
      tomography study of a 17-day-old male human with exstrophy was also reconstructed
      three dimensionally. The bony pelvis and pelvic floor muscular anatomy of both
      subjects were then examined and compared. RESULTS: On gross examination, a
      similar appearance of classic bladder exstrophy in the rhesus monkey and human
      newborn were noted, including an open exposed bladder, associated penile
      epispadias, and widely separated pubic bones. The evaluation of the three
      dimensional models showed a similar orientation of the bony pelvis in both the
      rhesus and the human newborn. The iliac wings were significantly rotated outward,
      and the sacroiliac joint was 10 degrees wider than that seen in normal children.
      The exstrophy pelvic floor in both the rhesus and the newborn was markedly
      flattened, with approximately 33% of the muscle located anterior to the rectum to
      support the pelvic structures (normal children have 50% of their levator ani
      anterior to the rectum). CONCLUSIONS: By using advancements in imaging
      modalities, this study illustrated that naturally occurring classic bladder
      exstrophy in the human newborn and rhesus monkey were identical in both external
      appearance and internal anatomy.

PMID- 11834382
TI  - Bilateral laparoscopic adrenalectomy: retroperitoneal and transperitoneal
      approaches.
AB  - OBJECTIVES: To report our experience with bilateral laparoscopic adrenalectomy
      using either the retroperitoneal or the transperitoneal approach. METHODS:
      Between June 1998 and October 2000, 6 consecutive patients with bilateral adrenal
      disease (Cushing syndrome in 4, pheochromocytoma in 1, and solitary adrenal
      metastases in 1) underwent bilateral laparoscopic adrenalectomy by way of the
      retroperitoneal or transperitoneal approach. Bilateral adrenalectomy was
      performed either synchronously (4 patients) or in a staged manner (2 patients).
      RESULTS: All laparoscopic procedures were performed successfully. For the
      bilateral synchronous cases (n = 4) and metachronous cases (n = 4), the median
      surgical time was 278 and 195 minutes, blood loss was 175 and 125 mL, resumption
      of oral intake and ambulation required less than 1 day for both groups, and
      postoperative narcotic requirement comprised 14 and 10 mg morphine sulfate
      equivalent, respectively. For the synchronous and metachronous cases, the
      hospital stay was 1.5 and less than 1 day and convalescence was 3 and 2.5 weeks,
      respectively. An intraoperative surgical complication (adrenal vein bleeding)
      occurred in 1 case, but did not require open conversion. No postoperative
      complications or rehospitalization occurred. The retroperitoneal approach was
      used in 3 of the 4 bilateral synchronous and 3 of the 4 bilateral metachronous
      cases. In both synchronous and metachronous cases, the actual surgical time,
      blood loss, time to oral intake and ambulation, postoperative analgesia use,
      hospital stay, and convalescence of the transperitoneal approach were well within
      the range of those of the retroperitoneal approach. CONCLUSIONS: Retroperitoneal
      and transperitoneal bilateral laparoscopic adrenalectomy is feasible, safe, and
      results in minimal postoperative morbidity.

PMID- 11834383
TI  - Early repeated exploration after laparoscopic urologic surgery: comparison of
      clinical, radiologic, and surgical findings.
AB  - OBJECTIVES: To correlate the clinical scenarios and radiographic findings with
      the operative findings in patients who underwent repeated exploration to define a
      management strategy. Postoperative complications after laparoscopy may cause
      diagnostic challenges because of atypical presentation. METHODS: We
      retrospectively reviewed the records from 1226 urologic laparoscopic procedures
      between July 1993 and July 2000. We compared the clinical, radiologic, and
      surgical findings of patients who underwent repeated exploration within the first
      month after laparoscopy. RESULTS: During the study period, 9 patients (0.7%) were
      taken back to the operating room for repeated exploration. The median time for
      the appearance of symptoms was the second postoperative day. Eight patients were
      evaluated by computed tomography (CT) and one by both renal Doppler
      ultrasonography and MAG-3 renal perfusion scan. Repeated operations were
      laparoscopic in 4 and open in 5 patients. In all the patients evaluated by CT
      scan, the radiologic findings were consistent with the surgical findings. In the
      patients who underwent diagnostic laparoscopy because of the severity of clinical
      findings, despite negative CT findings, no abnormality was discovered at
      exploration. In 1 patient who was not evaluated by CT, duodenal perforation was
      detected at exploration. CONCLUSIONS: Clinical findings may not be sufficient for
      the decision of repeated operation for patients acutely ill after laparoscopy. CT
      findings correlated well with the findings at exploration. In cases in which no
      abnormality is detected by CT, it appears reasonable to withhold surgical
      exploration unless the clinical situation deteriorates.

PMID- 11834384
TI  - Schistosomal myelopathy: urologic manifestations and urodynamic findings.
AB  - OBJECTIVES: To describe the clinical and urodynamic features of patients with
      voiding dysfunction secondary to schistosomal myelopathy. Schistosomiasis mansoni
      is an endemic fluke infection in South America, the Caribbean, and Africa. In the
      United States and Europe, people may be infected mainly through travel to endemic
      areas and immigration of infected individuals. Clinical involvement of the spinal
      cord is a well-recognized complication of the disease. The typical manifestations
      are those of an acute transverse myelitis, with sudden onset of lower extremity
      neuropathy associated with bladder and bowel dysfunction. METHODS: We reviewed
      the records and urodynamic studies of 14 consecutive patients (10 men and 4
      women, age range 23 to 49 years) with schistosomal myelopathy confirmed by
      cerebrospinal fluid serology for S. mansoni, who were referred for evaluation of
      voiding dysfunction during a 2-year period. At the time of the urologic
      evaluation, 9 patients had chronic neurologic and urinary symptoms and 5 had
      recent onset of acute symptoms. The voiding function history, urologic
      complications, and outcomes after therapy for schistosomiasis were reviewed.
      RESULTS: Of the patients with acute disease (5 patients), the urologic symptoms
      included urinary retention (3 patients) and incontinence (2 patients). Three of
      them had concurrent lower back pain and lower limb neurologic deficits.
      Urodynamic studies were performed in 3 patients and revealed bladder areflexia in
      2 patients and detrusor hyperreflexia with external sphincter dyssynergia in 1
      patient. The patients were started on clean intermittent catheterization and
      received praziquantel and corticosteroids. Three patients had complete resolution
      of their symptoms, one recovered normal voiding function but the neurologic
      deficits persisted, and one had no clinical improvement. All patients with
      chronic schistosomal myelopathy presented with lower limb neurologic deficits of
      varying degrees and urinary symptoms, including difficulty emptying the bladder
      (7 patients), urinary incontinence (6 patients), and urgency and frequency (2
      patients). Laboratory and radiographic evaluation of patients with chronic
      disease revealed urinary tract infection in 5 patients, hydronephrosis in 2
      patients, and bladder calculi in 2 patients. Urologic management consisted of
      antibiotics, clean intermittent catheterization, anticholinergic medication, and
      stone removal, as appropriate. In 1 patient, conservative treatment failed and
      that patient required ileocystoplasty. CONCLUSIONS: Schistosomal myelopathy is a
      potential cause of severe voiding dysfunction secondary to spinal cord disease. A
      high index of suspicion is paramount because early medical intervention can abort
      the progression of neurologic deterioration.

PMID- 11834385
TI  - Value of testis biopsy in the diagnosis of systemic amyloidosis.
AB  - OBJECTIVES: To evaluate testis biopsy as a diagnostic tool in systemic
      amyloidosis, to assess how amyloidosis affects testicular tissue, and to examine
      the relationship between testicular amyloidosis and infertility. METHODS:
      Testicular biopsies from 72 patients with confirmed systemic amyloidosis were
      examined for amyloid deposition after Congo red and crystal violet staining. A
      rectal biopsy was also done in each case, and the results were compared with the
      testicular biopsy findings. RESULTS: Testicular amyloid deposition was detected
      in 62 (86.1%) of 72 patients. Fifty-one (85%) of 60 patients with secondary
      amyloidosis, 11 (91.7%) of 12 patients with primary amyloidosis, and 28 (87.5%)
      of 32 patients with familial Mediterranean fever showed amyloid deposition in the
      testis. Rectal biopsies were positive in 40 cases (55.6%). Only 4 of the 62
      patients with testicular amyloid showed normal spermatogenesis. The remaining 58
      exhibited abnormal spermatogenesis, and 77.7% of patients had seconder
      infertility. Of 62 patients with positive testis biopsies, 30 had serum
      creatinine levels less than 1.5 mg/dL, and 29 patients with testicular amyloid
      manifested nephrotic syndrome. CONCLUSIONS: The testis biopsy is a valuable and
      more sensitive method than rectal biopsy for diagnosing systemic amyloidosis. The
      results also showed that testicular amyloidosis causes infertility at a higher
      rate than expected.

PMID- 11834386
TI  - Utility of oral dissolution therapy in the management of referred patients with
      secondarily treated uric acid stones.
AB  - OBJECTIVES: Uric acid stones are best managed by chemolysis. Some patients with
      acutely symptomatic stones opt for endourologic therapies. The radiolucent nature
      of these stones makes secondary interventions difficult to plan. Computed
      tomography becomes the modality of choice to identify stone locations and size in
      these patients. We analyzed patients with uric acid stones referred to our stone
      center after primary treatment had failed to establish the efficacy of oral
      alkalinization therapy. METHODS: Eleven patients presented after one or more
      failed attempts to intervene for uric acid stones. Charts were reviewed for age,
      sex, time with stone before referral, medical therapies undertaken, number of
      antecedent urologic interventions, number of radiographic studies performed,
      subsequent procedures performed, and outcomes with a minimal follow-up of 6
      months. RESULTS: Eight patients were men and four presented with bilateral stone
      disease (overall, 15 involved upper tracts). Sixty-seven percent of patients had
      right-sided solitary calculi. All patients at presentation filled out urinary pH
      diaries. Of the 11 patients, 4 stated they had been prescribed oral alkaline
      therapy but were found to be noncompliant, 4 were never prescribed this therapy,
      and 3 took the medication sporadically. All patients were counseled on self
      dosing to maintain their urinary pH between 6.0 and 6.5 and to continue the
      diaries. Computed tomography scans were done in 9 patients, and intravenous
      urography and ultrasonography in the other 2 patients confirmed the stone burden.
      Only 3 patients (27%) required subsequent interventions (ureteroscopic laser
      lithotripsy). CONCLUSIONS: Secondarily referred patients with uric acid stones
      are best treated with medical therapy. These findings suggest that the initial
      medical regimens had failed because of noncompliance or lack of effective follow
      up by the primary urologist. Seventy-three percent of these patients had
      dissolution of the stones, requiring no further endourologic intervention.

PMID- 11834387
TI  - Comparison of costs and complications of radical and partial nephrectomy for
      treatment of localized renal cell carcinoma.
AB  - OBJECTIVES: To compare the complications and costs of radical and partial
      nephrectomy (PN) and to investigate the impact of increasing experience on costs
      and complications during a 7-year period. Nephron-sparing surgery has found
      increasing applications in the past decade. PN has achieved similar long-term
      results in localized renal cell carcinoma with respect to cancer control compared
      with radical nephrectomy (RN). However, data are limited on the direct comparison
      of complications and hospital costs between these two modalities. METHODS: A
      retrospective case-matched study was performed comparing 60 RNs and 60 PNs during
      a 7-year period with respect to complications and hospital costs. A longitudinal
      comparison was also performed between the various periods to assess the impact of
      surgical experience on these parameters. RESULTS: The mean length of stay was 6.4
      +/- 3 days in the RN group and 6.4 +/- 3.3 days in the PN group. The hospital
      costs were comparable between the two procedures during the observed interval.
      The mean operative time was 176.6 +/- 51.6 minutes for RN and 220.1 +/- 59.6
      minutes for PN (P = 0.0001). This difference was accentuated during the observed
      period. No differences were found in the blood loss and transfusion rates between
      the groups. The complication rate was 3.3% and 10% for RN and PN, respectively (P
      = 0.2). CONCLUSIONS: Our data suggest that RN and PN can be performed with a
      similar rate of complications and comparable hospital costs. This is of practical
      importance when comparing these modalities as treatment options for localized
      renal cell carcinoma.

PMID- 11834388
TI  - New aspect of photodynamic diagnosis of bladder tumors: fluorescence cytology.
AB  - OBJECTIVES: To establish a new diagnostic method for the detection and follow-up
      of bladder cancer that combines the principles of photodynamic diagnosis and
      urinary cytology. METHODS: We investigated 46 patients scheduled for
      transurethral resection of a bladder tumor immediately before the resection was
      carried out. After intravesical instillation of either 5-aminolevulinic acid
      (ALA) or hypericin, urinary cytology specimens were obtained. Induced
      fluorescence of urothelial cells was detected by fluorescence microscopy. The
      results were compared with the conventional cytologic and histologic findings.
      RESULTS: In the 46 patients, 42 cases of urothelial carcinoma and 4 cases of
      nonspecific inflammation were diagnosed. Of the 42 patients with cancer, 19 had
      Stage Ta, 9 had T1, 3 had carcinoma in situ, and 11 had invasive bladder cancer.
      The grading was G1 in 17 patients, G2 in 6 patients, and G3 in 19 patients. In 38
      cases we instilled ALA and in 8 hypericin. All 4 patients diagnosed with
      nonspecific inflammation had received ALA. We detected ALA-induced fluorescence
      in 34 of 38 cases. One of the four histologically negative cases had a false
      positive finding and 1 case of urothelial carcinoma did not show fluorescence.
      After instillation of hypericin we could detect induced fluorescence in all
      cases. CONCLUSIONS: Our first results suggest that fluorescence cytology is more
      sensitive than other noninvasive tests. After additional investigation, it may
      become a valuable diagnostic method and may reduce the number of cystoscopies in
      the follow-up of bladder tumors.

PMID- 11834389
TI  - Is repeated transurethral resection justified in patients with newly diagnosed
      superficial bladder cancer?
AB  - OBJECTIVES: To assess the value of repeated transurethral resection (TUR) in
      patients with newly diagnosed superficial bladder cancer. METHODS: A second TUR
      was performed in 110 consecutive patients (24 women and 86 men) with newly
      diagnosed superficial bladder cancer. The mean age was 66 years (range 30 to 85).
      A second TUR was performed within 4 to 6 weeks after the initial TUR. After the
      first TUR, the pathologic stage was pTa in 31 patients (28%), pT1 in 76 (70%),
      and carcinoma in situ in 3 (2%). The pathologic records of the second TUR were
      reviewed and compared with the findings of the first operation. RESULTS:
      Cystoscopy before the second TUR was negative in 79 patients. Of these cases, 14
      (17.7%) had cancer histologically. The second TUR was negative in 70 patients
      (63.6%). Twenty-two (20%) had residual cancer of the same stage, 9 (8.2%) had a
      lower stage, and 9 (8.2%) had a higher stage. Of 31 patients with Stage pTa and
      76 patients with Stage pT1 at the first TUR, 19 (61.3%) and 51 (67.1%) had a
      negative second TUR, respectively. CONCLUSIONS: We recommend a second TUR for
      patients with superficial bladder cancer for several reasons. A negative second
      TUR provides important prognostic information. In addition, removal of residual
      cancer is achieved early. Finally, patients with pT1 G3 tumors are at high risk
      of residual, or even invasive, cancer and should be offered definitive therapy as
      early as possible.

PMID- 11834390
TI  - Routine bladder biopsy after bacille Calmette-Guerin treatment: is it necessary?
AB  - OBJECTIVES: To evaluate the need for routine biopsy at first follow-up after
      intravesical bacille Calmette-Guerin (BCG) therapy for superficial transitional
      cell cancer of the bladder (TCCB). We examined the potential role of voided urine
      cytology and cystoscopy as screening tools to determine which patients should
      undergo biopsy. METHODS: The records of 71 patients with TCCB who received a
      total of 95 courses of BCG were reviewed. The pathology findings before BCG and
      the cystoscopic, voided cytologic, and biopsy results after BCG were recorded.
      RESULTS: In 54 cases, the cystoscopic and/or cytologic findings were abnormal. In
      19 (35%) of these 54 cases, TCCB was found on biopsy after BCG. In 41 cases, both
      cystoscopy and cytology were normal. In 1 of these 41 cases, a small superficial
      low-grade TCCB was found on biopsy. An abnormality on voided cytology or
      cystoscopy was more likely to occur after treatment for carcinoma in situ.
      CONCLUSIONS: Patients with papillary TCCB who have negative cystoscopic and
      negative urine cytologic results can safely be spared routine transurethral
      bladder biopsy with its associated cost and morbidity. However, patients with
      carcinoma in situ are very likely to have persistent abnormal cytologic or
      abnormal cystoscopic findings warranting investigation with biopsy and may
      benefit from routine scheduled biopsy.

PMID- 11834391
TI  - Long-term follow-up of G3T1 transitional cell carcinoma of the bladder treated
      with intravesical bacille Calmette-Guerin: 18-year experience.
AB  - OBJECTIVES: Immunotherapy with bacille Calmette-Guerin (BCG) has been proposed in
      the past decade as first-line treatment for high-grade superficial bladder cancer
      (G3T1). We report our 18-year experience in the treatment of patients with G3T1
      bladder cancer. METHODS: From January 1989 to July 1997, 670 patients underwent
      transurethral resection for superficial bladder cancer. Eighty-one patients (12%)
      had G3T1 tumors. All of these patients were treated with an innovative schedule
      of Pasteur strain BCG followed by maintenance BCG therapy. Treatment consisted of
      four cycles of 6 instillations per cycle of BCG. The first cycle was administered
      weekly x 6, the second was given every 2 weeks x 6, the third cycle was given
      monthly x 6, and the fourth was given every 3 months x 6 instillations. RESULTS:
      Sixty-nine patients (84%) completed at least the first two cycles. At a median
      follow-up of 76 months (range 30 to 197), the overall recurrence rate was 33% (27
      of 81). The median time to recurrence was 20 months (range 5 to 128). Of these
      patients, 12 (15%) had progression at a median follow-up of 16 months (range 8 to
      58). Cystectomy was required in 7 patients (8%). Death from disease occurred in 5
      (6%) of 81 patients. One patient died of adenocarcinoma at the
      ureterosigmoidostomy site. Sixty patients (74%) were alive at a median follow-up
      of 79+ months (range 15 to 182). Of these, 56 (69%) were alive with a functioning
      bladder. CONCLUSIONS: Conservative treatment with BCG is a reasonable approach
      for patients with primary G3T1 transitional cell carcinoma of the bladder. The
      long-term results of BCG therapy are good. Cystectomy may not be justified as the
      therapy of choice in first-line treatment of high-grade superficial carcinoma of
      the bladder.

PMID- 11834392
TI  - Prognostic-factors-based risk-stratification model for invasive urothelial
      carcinoma of the urinary bladder in Taiwan.
AB  - Objectives. To develop a prognostic-factors-based predictive model for invasive
      urothelial carcinoma of the urinary bladder derived from statistical comparison
      of clinical characteristics.Methods. The medical records for patients with
      invasive urinary bladder urothelial carcinoma were reviewed. Clinical data for
      age, sex, serum lactate dehydrogenase, creatinine, albumin, alkaline phosphatase,
      alanine aminotransferase, total bilirubin and hemoglobin levels, white blood cell
      and platelet counts, positive urine cytology, Eastern Cooperative Oncology Group
      performance status score, tumor size, histologic grading, T stage, presence of
      lymph node metastases, squamous differentiation, hydronephrosis, prostatic
      involvement, Charlson comorbidity index, surgical procedures, and adjuvant
      chemotherapy status were recorded. Univariate and multivariate analyses were
      performed to test independent factors for prediction of survival and disease
      recurrence.Results. After univariate and multivariate analyses, six independent
      prognostic factors were found: T stage, grading, prostatic involvement, Eastern
      Cooperative Oncology Group performance status score, and pretreatment serum
      creatinine and albumin levels. A scoring system was developed on the basis the
      relative risk associated with the proposed prognostic factors and patients were
      stratified into three groups according to their scores, with statistically
      significant prognostic differences revealed for each of the between-group
      comparisons. Independent factors affecting recurrence-free survival and best
      predicted disease recurrence were pretreatment serum creatinine, T stage, and
      surgical procedure.Conclusions. This prognostic-factors-based risk-stratification
      model for invasive urothelial carcinoma of the urinary bladder may help
      clinicians predict outcome and select the most appropriate therapeutic
      modalities. The incidence of recurrent disease is significantly higher for
      patients with poor renal function before treatment or advanced T stage and those
      undergoing transurethral tumor resection instead of radical cystectomy.

PMID- 11834395
TI  - Transitional cell carcinoma in patients with spinal cord injury: a high risk
      malignancy?
AB  - OBJECTIVES: To study bladder cancer incidence in patients with spinal cord injury
      (SCI) in Germany, Switzerland, and Austria. SCI is associated with neurogenic
      bladder dysfunction. These patients are at an increased risk of developing
      bladder malignancies. METHODS: A questionnaire was mailed to all SCI centers in
      these countries. The number of patients with SCI treated between 1995 and 1999,
      and the data of all patients with SCI with bladder cancer were recorded. RESULTS:
      The charts of 43,561 patients were reviewed. Of these, 48 patients (0.11%)
      developed bladder cancer. The data of 8 female and 29 male patients were fully
      available. The mean age was 53.3 years. Bladder management was reflex voiding in
      18 patients, intermittent catheterization in 12 patients, and an indwelling
      catheter in 7 patients. Twelve patients were smokers. The mean time between SCI
      and the first bladder cancer diagnosis was 22.6 years. Thirty-two percent had
      superficial cancers, 8% had carcinoma in situ, and 60% presented with muscle
      infiltrating tumors; 81% had urothelial cancer and 19% squamous cell cancer.
      Thirteen patients rarely had urinary tract infections (UTIs), 9 had more than 10
      UTIs annually, and 15 had chronic UTIs. CONCLUSIONS: The bladder cancer incidence
      in patients with SCI and in the general population is comparable. More than 60%
      of the patients with SCI, however, initially presented with muscle-infiltrating
      bladder cancer. Indwelling catheters and chronic UTIs were common in patients
      with bladder cancer. Immunologic pathologic mechanisms and a prolonged exposure
      to carcinogens may be involved in bladder cancer carcinogenesis in patients with
      SCI.

PMID- 11834396
TI  - Quality-of-life impact of lower urinary tract symptom severity: results from the
      Health Professionals Follow-up Study.
AB  - OBJECTIVES: To estimate the magnitude of the quality-of-life impact of lower
      urinary tract symptom (LUTS) severity using a large (n = 8406) sample of U.S. men
      participating in the Health Professionals Follow-up Study. METHODS: Multiple
      regression modeling was used to estimate the relative quality-of-life burden of
      different levels of LUTS severity (defined using the American Urological
      Association Symptom Index as none-mild symptoms, 0 to 7; low moderate, 8 to 14;
      high moderate, 15 to 19; and severe, 20 to 35) and to compare these with age
      matched U.S. male norms. A standardized and validated measure of both LUTS
      severity (the American Urological Association Symptom Index) and a widely used,
      standardized, multidimensional measure of quality of life (Short Form 36) were
      used. In addition, the relative impact of severe LUTS on the quality of life was
      compared with that experienced for other chronic illness conditions (diabetes,
      angina, hypertension, gout). RESULTS: The results showed that high-moderate LUTS
      was associated with small to moderate deficits in anxious and depressed mood and
      poorer role functioning related to emotional problems arising from illness.
      Severe LUTS was associated with additional quality-of-life deficits related to
      vitality and the ability to work and carry out daily tasks as a result of
      illness. Comparisons of the severe LUTS patient group with four other chronic
      illness groups showed vitality/energy, in particular, but also role functioning
      and depressed and anxious feelings, to be poorer in the severe LUTS group.
      CONCLUSIONS: Men with high-moderate and severe LUTS identified in a large U.S.
      cohort have a poorer health status in several important quality-of-life
      dimensions. The detection and effective treatment of LUTS may substantially
      improve the health status for these men in these dimensions.

PMID- 11834397
TI  - Prostate-specific antigen testing in black and white men: an analysis of medicare
      claims from 1991-1998.
AB  - OBJECTIVES: To describe the trends in prostate-specific antigen (PSA) use and
      associated cancer detection among black and white Medicare beneficiaries older
      than 65 years during the calendar period from January 1991 through December 1998.
      METHODS: Medicare claims data were linked with cancer registry data from the
      Surveillance, Epidemiology and End Results program of the National Cancer
      Institute. Data from a 5% random sample of men without a diagnosis of prostate
      cancer were combined with data from prostate cancer cases diagnosed during the
      calendar period from 1991 to 1998. PSA tests conducted after a diagnosis of
      prostate cancer were excluded. RESULTS: PSA use has stabilized among white men,
      reaching an annual rate of 38% by 1995 and remaining at this level through 1998.
      The annual rate of use among black men reached 31% by 1998, but was still
      increasing at that time. By 1996, at least 80% of tests in both blacks and whites
      were second or later tests. By the end of 1996, 35% of white men and 25% of black
      men were undergoing testing at least biannually or more frequently. In 1996, 83%
      of diagnoses in whites and 77% in blacks were preceded by a PSA test.
      CONCLUSIONS: Older black men lag slightly behind older white men in their use of
      the PSA test; however, annual testing rates in blacks have yet to stabilize. In
      both race groups, an overwhelming majority of diagnoses are associated with a PSA
      test, whether for screening or diagnostic purposes. Regular screening rates in
      blacks are substantially lower than in whites, but the regular screening rates
      are relatively low in both race groups. Should PSA screening prove efficacious,
      efforts to promote regular use among both black and white men will likely be
      needed.

PMID- 11834398
TI  - Free/total PSA ratio does not improve prediction of pathologic stage and
      biochemical recurrence after radical prostatectomy.
AB  - OBJECTIVES: Despite several publications, the ability of the free/total (F/T)
      prostate-specific antigen (PSA) ratio to predict the pathologic extension of
      prostate cancer is still a matter of controversy. In addition, its ability to
      predict biochemical recurrence after radical prostatectomy has not yet been
      reported. METHODS: Since January 6, 1996, the F/T PSA ratio was prospectively
      measured preoperatively in 343 patients undergoing radical prostatectomy as the
      first treatment for localized prostate cancer. RESULTS: The ability to predict
      organ-confined disease was measured by receiver operating characteristic
      analysis. The areas under the curve were 0.66 for PSA density, 0.61 for total
      PSA, 0.60 for Gleason score, and 0.587 for the F/T PSA ratio. In multiple
      logistic regression analyses, the F/T PSA ratio was not a relevant predictor of
      organ-confined disease (Wald statistic 0.345 for P = 0.55). Similar results were
      obtained in the subgroup of patients with a PSA level between 2.5 and 10 ng/mL.
      The biochemical survival for the 270 patients who did not receive adjuvant
      therapy was 86% at 61 months. Statistically significant univariate predictors (P
      <0.05) of PSA recurrence were pT stage (log-rank 18.2) and Gleason grade (log
      rank 8.8). The F/T PSA ratio was not a significant predictor of recurrence in the
      univariate analysis (log-rank 3.6 for P = 0.314) and in multivariate analysis
      (Wald statistic 0.2 for P = 0.97). CONCLUSIONS: These results suggest that the
      F/T PSA ratio is not helpful for the prediction of organ-confined disease and PSA
      recurrence after radical prostatectomy.

PMID- 11834399
TI  - Comparative evaluation of total PSA, free/total PSA, and complexed PSA in
      prostate cancer detection.
AB  - OBJECTIVES: To compare the performance of prostate-specific antigen (PSA), the
      free/total PSA (F/T PSA) ratio, and complexed PSA (cPSA) in prostate cancer
      detection. METHODS: Five hundred thirty-five patients evaluated at the UROMED
      prostate cancer detection clinic had total PSA, free PSA, and cPSA measured
      before undergoing transrectal ultrasonography and sextant prostate biopsies. A
      direct comparison was performed between the different PSA assays to evaluate
      their ability to detect prostate cancer. RESULTS: Of the 535 patients evaluated,
      38.1% had prostate cancer detected. The mean age of the entire population was
      63.6 years (range 35 to 86). Abnormal digital rectal examination findings were
      present in 33.4% of the patients. The mean and median values of PSA and cPSA were
      significantly higher and the F/T PSA ratio was lower in patients with prostate
      cancer. The F/T PSA ratio performed better than either cPSA or total PSA. A
      higher specificity was observed with the F/T PSA ratio than with cPSA using
      either the entire patient population or subsets of patients with PSA levels
      between 4.0 and 10 ng/mL or 4.0 to 6.0 ng/mL. CONCLUSIONS: The use of the F/T PSA
      ratio offers improved prostate cancer detection compared with either cPSA or
      total PSA.

PMID- 11834400
TI  - Practice trends in the management of prostate disease by family practice
      physicians and general internists: an internet-based survey.
AB  - OBJECTIVES: To assess, using an Internet-based survey, the practice patterns of
      primary care physicians in the management of prostate disease and to assess the
      differences between family physicians and general internists. Prostate cancer and
      benign prostatic hyperplasia are common in the elderly population. The optimal
      management of these diseases is debated. METHODS: An 18-item survey was designed
      and administered on an Internet website. Members of the Society of General
      Internal Medicine and members of the Illinois, North Carolina, and New York
      chapters of the Academy of Family Physicians were surveyed. RESULTS: A total of
      354 responses were obtained from 381 primary care physicians who viewed the
      survey web page. For patients 50 years old and older, 75% of physicians (87% of
      family physicians and 69% of general internists; P <0.001) recommended annual
      prostate cancer screening with digital rectal examination and 49% (67% of family
      physicians and 40% of general internists; P <0.001) recommended annual prostate
      cancer screening with prostate-specific antigen measurement. For patients
      diagnosed with prostate cancer, 76% of the primary care physicians estimated that
      less than one half of their patients are seen by a radiation oncologist. For the
      treatment and/or prevention of prostate cancer, 62% of physicians surveyed (76%
      of family physicians and 55% of general internists; P <0.001) believe there is a
      potential role for alternative herbal and nutritional therapies. CONCLUSIONS:
      Compared with general internists, family physicians are more likely to screen for
      prostate cancer and are more likely to believe there is a role for alternative
      therapies for prostate cancer.

PMID- 11834401
TI  - Rates of unconventional medical therapy use in patients with prostate cancer:
      standard history versus directed questions.
AB  - OBJECTIVES: The use of unconventional medical therapies (UMTs) in the general
      population has increased dramatically in the past decade. Studies have estimated
      that 9% to 64% of patients with cancer use UMTs, and many do not disclose this
      information to their physicians. This study was designed to evaluate the rates of
      UMT use by patients with prostate cancer revealed by standard versus directed
      questioning and to identify demographic markers that may predict use. METHODS: A
      prospective study of 287 consecutive patients with cancer presenting to the
      Department of Radiation Oncology was performed. The prostate cancer population
      was 29% (84 of 287) of the total cancer patient population. Each patient
      underwent the standard history interview, including questions regarding
      prescription and over-the-counter medication. At the completion of the standard
      history interview, patients were then asked a set of directed questions regarding
      the use of UMTs. RESULTS: Of the 84 patients with prostate cancer, 31 (37%) used
      unconventional therapies. The standard history revealed that 6 (19%) of 31 used
      UMTs, and directed questioning revealed an additional 25 patients (81%) used UMTs
      in the study population (P <0.001). Of those using UMTs, 65% used megavitamins,
      49% used herbal remedies, 13% used meditation or guided imagery, and 20% used
      nonherbal natural supplements. CONCLUSIONS: UMT use is prevalent among patients
      with prostate cancer. Some of these treatments may have a potential biologic
      impact on tumor behavior, therapeutic endpoints, and measured prostate-specific
      antigen values. The use of directed questioning during the patient evaluation
      significantly increases the physician's ability to identify patients with
      prostate cancer using UMTs.

PMID- 11834402
TI  - Increase of bone alkaline phosphatase after androgen deprivation therapy in
      patients with prostate cancer.
AB  - OBJECTIVES: To evaluate the behavior of bone alkaline phosphatase (BAP) after
      androgen deprivation therapy in patients with prostate cancer. METHODS: BAP was
      determined in the serum of 35 patients with nonmetastatic prostate cancer before
      maximal androgen blockade. During 5 years of follow-up, BAP was determined
      annually. A subset of 36 patients who underwent radical prostatectomy as the only
      treatment for prostate cancer was selected as a control group. RESULTS: The mean
      pretreatment BAP serum concentration was similar in both groups (10.8 and 10.4
      ng/mL, P >0.05). However, after 5 years, the mean BAP serum concentration
      increased 64.8% in the study group (from 10.8 to 17.6 ng/mL, P < 0.001); it
      remained stable in the control group (from 10.4 to 10.4 ng/mL). The increase of
      serum BAP in patients receiving androgen deprivation was 32.4% during the first
      year (from 10.8 to 14.3 ng/ml), 16.7% during the second (from 14.3 to 16.1
      ng/mL), 7.4% during the third (from 16.1 to 16.9 ng/mL), 5.5% during the fourth
      (from 16.9 to 17.3 ng/mL), and 2.8% during the fifth year (from 17.3 to 17.6
      ng/mL). CONCLUSIONS: Androgen deprivation produces an increase in the BAP serum
      concentration. A major increase seems to be produced during the first year of
      follow-up and thereafter this increase is reduced around 50% annually.

PMID- 11834403
TI  - Cavernous and systemic plasma levels of norepinephrine and epinephrine during
      different penile conditions in healthy men and patients with erectile
      dysfunction.
AB  - OBJECTIVES: To examine and compare the courses of norepinephrine (NE) and
      epinephrine (E) plasma levels in the systemic and cavernous blood taken during
      different penile conditions from healthy men and a group of patients with
      erectile dysfunction (ED). Knowledge concerning the neurophysiology of penile
      erection has improved tremendously during the past two decades. However, only few
      in vivo studies on human peripheral neurotransmission have been carried out to
      date. METHODS: Fifty-three healthy adult male subjects and 47 patients with ED of
      different etiologies were exposed to erotic stimuli to elicit penile tumescence
      and, in the group of healthy subjects, rigidity. Whole blood was simultaneously
      aspirated from the corpus cavernosum and the cubital vein during different penile
      conditions. Plasma levels of NE and E were determined by means of a
      radioimmunoassay. RESULTS: In the healthy subjects, a significant reduction of NE
      in cavernous plasma was detected from flaccidity (362 +/- 173 pg/mL) to rigidity
      (248 +/- 122 pg/mL), followed by an increase in the detumescence phase (336 +/-
      199 pg/mL). Changes in NE levels in the peripheral plasma were less pronounced.
      Cavernous E levels significantly increased from flaccidity (47 +/- 41 pg/mL) to
      tumescence (130 +/- 106 pg/mL) and dropped from rigidity (113 +/- 67 pg/mL) to
      detumescence (76 +/- 57 pg/mL). The course of systemic E plasma levels was
      similar to that in the cavernous blood. In contrast, median NE levels in the
      systemic and cavernous blood of the ED group slightly increased from flaccidity
      to tumescence (from 199 +/- 88 pg/mL to 210 +/- 99 pg/mL and from 273 +/- 140
      pg/mL to 278 +/- 118 pg/mL, respectively). CONCLUSIONS: In healthy men, penile
      erection is accompanied by a reduction of NE in the cavernous blood and a rise in
      E levels in the peripheral and cavernous blood. That NE levels in the cavernous
      and systemic blood increase during sexual arousal in patients with ED might be an
      indication of a somatic dysregulation in sympathetic transmission or alterations
      of NE reuptake mechanisms as a cause of impaired erectile function.

PMID- 11834404
TI  - Presence of the eggshell sign in obstructive uropathy.
AB  - OBJECTIVES: To analyze the relationship between hydronephrosis due to urinary
      tract obstruction and the presence of the sonographic eggshell sign, which is a
      recently described crescent of increased echogenicity at the caliceal/parenchymal
      interface and possibly an indicator of raised intrarenal pressure. METHODS: All
      patients presenting between 1996 and 1999 for surgical management of
      pelviureteral junction obstruction or congenital posterior urethral obstruction
      had films reviewed for the presence of the eggshell sign. RESULTS: Of 94
      patients, 40 presented postnatally and 54 had hydronephrosis detected on the
      antenatal ultrasound scan. Of the postnatal group, 16 (40%) had urethral
      obstruction, of whom 4 (25%) displayed the eggshell sign; in the 24 with
      pelviureteral junction obstruction, the echogenic pericaliceal crescent was seen
      in 5 (20.8%). Of the 54 in the prenatal group, 8 (15.4%) were found to have
      urethral obstruction, 5 (62.5%) of whom demonstrated the eggshell sign. Of the 46
      prenatally diagnosed patients with pelviureteral junction obstruction, 31 (70.5%)
      displayed the eggshell sign before birth; we were unable to satisfactorily review
      2 patients' ultrasound scans. CONCLUSIONS: Antenatally diagnosed hydronephrosis
      due to significant urinary tract obstruction seems to be related to the
      appearance of the eggshell sign on ultrasonography, particularly in those
      patients with pelviureteral junction obstruction. Those patients without
      significant caliceal distension and those with renal dysplasia or severe
      hydronephrosis with low-pressure kidneys were less likely to display the eggshell
      sign. Although the association with other causes of hydronephrosis is unknown, we
      believe these figures support the need for further investigation of the eggshell
      sign as a marker of raised intrarenal pressure to possibly provide another data
      point in the sonographic evaluation of congenital hydronephrosis.

PMID- 11834405
TI  - Versatility of reconfigured-colon-segment technique for urinary reconstruction
      requiring use of tubular structures.
AB  - INTRODUCTION: When a colon segment is used for urinary reconstruction and a
      tubular structure is necessary, the option for the tubular structures is limited.
      We prepared a short colon segment in advance for creating a reconfigured tube.
      TECHNICAL CONSIDERATIONS: Short colon segments are separated beforehand from the
      edges of the main colon segment for a continent urinary reservoir or augmentation
      cystoplasty. The short segments are either reconfigured, if necessary, into
      tubular structures to produce a continent valve or to replace a ureteral defect
      or discarded if they prove not to be needed. The number of short segments can be
      predicted on the basis of the clinical situation before and during the operation.
      CONCLUSION: Preparation of short colon segments is useful for urinary
      reconstruction using a colon segment that might require a number of tubular
      structures. The technique provides versatility and flexibility in difficult
      clinical conditions.

PMID- 11834406
TI  - Adult testicular sarcoma: presentation, evaluation, and treatment.

PMID- 11834415
TI  - Intraluminal pressure changes in vivo in the middle and distal pig ureter during
      propagation of a peristaltic wave.
AB  - OBJECTIVES: To establish the characteristics of mechanical activity during
      ureteral peristalsis and unidirectional bolus transport, pressure changes in the
      middle and distal (juxtavesical and ureterovesical junction) porcine ureter were
      quantified in vivo. METHODS: Five female New Yorkshire pigs (50 to 60 kg) were
      studied under halothane anesthesia. The endoscopic approach was used to position
      an 8-channel 6 F perfusion catheter under direct vision into the distal ureter by
      way of the orifice. Ureteral activity was studied in two separate sessions at 1
      week intervals. The pressure, propagation velocity, and length of the peristaltic
      waves were analyzed. RESULTS: The average maximal pressure in a not previously
      instrumented ureter amounted to 35.7 +/- 1.2 cm H(2)O in the mid-ureter, and
      decreased to 19.4 +/- 1.3 cm H(2)O in the juxtavesical ureter (P < 0.001) and
      further to 7.2 +/- 1.0 cm H(2)O (P < 0.001) in the submucosal segment. The
      propagation velocity of the peristaltic wave through the ureter was 2.1 +/- 1.3
      cm/s. The length of the pressure peak was 5.9 +/- 1.6 cm. CONCLUSIONS: A ureteral
      peristaltic contraction wave travels at approximately 2 cm/s and is approximately
      6 cm long. It is responsible for the unidirectional transport of a urinary bolus
      and itself acts as an "active" antireflux mechanism. The maximal pressure in the
      lumen of the ureter decreased from proximally to distally, but remains
      sufficiently high at the ureterovesical junction to prevent retrograde urine
      leakage when the ureter empties its urinary bolus into the bladder and the
      orifice is open.

PMID- 11834416
TI  - Efficacy of antimicrobial-impregnated silicone sections from penile implants in
      preventing device colonization in an animal model.
AB  - OBJECTIVES: To assess, in an animal study, the efficacy of minocycline/rifampin
      impregnated silicone sections of pump bulbs from penile implants in preventing
      device colonization by Staphylococcus aureus. Infection constitutes a very
      serious complication of penile implants. METHODS: Minocycline/rifampin
      impregnated and control silicone pump bulb sections from penile implants were
      each inoculated with about 10(3) to 10(4) colony-forming units of S. aureus.
      After 8 hours of incubation with bacteria at room temperature, the test devices
      were allowed to dry for 30 minutes, and then subcutaneously implanted in the
      backs of rabbits. Eleven rabbits each received a total of six devices. The wounds
      were sutured, and the rabbits were monitored daily, then killed at 2 days after
      surgery. In vitro zones of inhibition against S. aureus by the
      minocycline/rifampin-impregnated and control devices were also determined.
      RESULTS: All of the six tested antimicrobial-impregnated devices but none of the
      control devices produced zones of inhibition in vitro against S. aureus (mean
      zone of inhibition by antimicrobial-impregnated devices of 23 mm). The
      antimicrobial-impregnated devices retrieved from rabbits were sixfold less likely
      than were the control devices to be colonized with S. aureus (2 [6%] of 33 versus
      11 [33%] of 33, respectively; P = 0.011). CONCLUSIONS: The results of this animal
      study indicate that minocycline/rifampin-impregnated pump bulb sections from
      penile implants provide antimicrobial activity in vitro against S. aureus and
      protect against staphylococcal colonization of devices implanted for 2 days in
      animals.

PMID- 11834417
TI  - Cathepsins B, H, and L activities in urine of patients with transitional cell
      carcinoma of the bladder.
AB  - OBJECTIVES: Cathepsin B, H, and L (CB, CH, CL) are lysosomal proteolytic enzymes
      that belong to the group of cysteine proteinases. The imbalance between
      proteinases and their inhibitors is believed to correlate with tumor progression
      and shortened patient survival. In transitional cell carcinoma (TCC) only limited
      data have been published. METHODS: Using spectrofluorometric assays, catalytic
      activities of CB, CH, and CL in urine were measured to evaluate the potential
      diagnostic and prognostic value for patients with TCC of the bladder. Second
      morning urine was collected and used for measurements. CB, CH, and CL activities
      were determined for groups of patients with superficial disease (Ta-1, n = 43)
      and muscle-invasive tumors (T2, n = 18; or greater than T2, n = 9), as well as
      for different tumor grades (G1, n = 12; G2, n = 26; and G3, n = 31). For
      comparison, 14 urine samples from patients with bladder inflammation and 43
      samples from a control group were also included. RESULTS: Compared with the
      control group, patients with superficial Stage Ta-T1 disease and muscle-invasive
      Stage T2 or greater disease, as well as patients with G3 tumors, revealed
      significantly higher urinary CL activity. CB and CH did not show any tumor
      related activity increase. CB was significantly lower in patients with
      nonrecurrent tumors. CONCLUSIONS: These results suggest that elevated levels of
      CL in urine might be indicative of a cellular proteolytic imbalance in TCC of the
      bladder and may have a prognostic and/or diagnostic value.

PMID- 11834421
TI  - Pancreas duodenum homeobox-1 regulates pancreas development during embryogenesis
      and islet cell function in adulthood.
AB  - Pancreas duodenum homeobox-1 (PDX-1) (also known as insulin promoter factor-1,
      islet/duodenum homeobox-1, somatostatin transactivating factor-1, insulin
      upstream factor-1 and glucose-sensitive factor) is a transcription factor encoded
      by a Hox-like homeodomain gene. In humans and other animal species, the embryonic
      development of the pancreas requires PDX-1, as demonstrated by the identification
      of an individual with pancreatic agenesis resulting from a mutation that impaired
      the transcription of a functionally active PDX-1 protein. In adult subjects, PDX
      1 is essential for normal pancreatic islet function as suggested by its
      regulatory action on the expression of a number of pancreatic genes, including
      insulin, somatostatin, islet amyloid polypeptide, the glucose transporter type 2
      and glucokinase. Furthermore, heterozygous mutations of PDX-1 have been linked to
      a type of autosomal dominant form of diabetes mellitus known as maturity onset
      diabetes of the young type 4. The dual action of PDX-1, as a differentiation
      factor during embryogenesis and as a regulator of islet cell physiology in mature
      islet cells, underscores the unique role of PDX-1 in health and disease of the
      human endocrine pancreas.

PMID- 11834422
TI  - Angiogenesis of endocrine gland tumours--new molecular targets in diagnostics and
      therapy.
AB  - Angiogenesis is one of the key stages in the development of neoplastic tumours,
      in which a small group of mutated cells transforms into a large malignant tumour
      metastasising to the neighbouring tissues and organs. The studies on the
      significance of neoangiogenesis in the progression of endocrine gland neoplasms
      have recently become one of the most rapidly evolving branches of molecular
      endocrinology. The induction of angiogenesis has been demonstrated to result from
      the imbalance between positive and negative factors which control this process.
      Our paper presents the results of current studies on the role of factors such as
      molecular markers of angiogenesis (e.g. vascular endothelial growth factor and
      basic fibroblast growth factor), metalloproteinases (which regulate the
      decomposition of the extracellular matrix) and their inhibitors, and adhesive
      molecules (e.g. soluble vascular cellular adhesion molecule-1 and soluble
      intracellular adhesion molecule-1) in the pathogenesis and diagnostics of
      endocrine gland tumours in humans. Also, we discuss new therapeutic strategies
      for inhibiting the growth of neoplasms by blocking the formation of blood vessels
      using angiogenesis antagonists, which inhibit various stages of angiogenesis.
      More and more data are being accumulated suggesting that these preparations
      could, in the near future, be used in the pharmacotherapy of some endocrine gland
      neoplasms.

PMID- 11834423
TI  - Smoking and thyroid disorders--a meta-analysis.
AB  - BACKGROUND: Smoking has been associated with Graves' disease, but it remains
      unclear if the association is present in other thyroid disorders. OUTCOME
      VARIABLES: Graves' disease, Graves' ophthalmopathy, toxic nodular goitre, non
      toxic goitre, post-partum thyroid disease, Hashimoto's thyroiditis, or
      hypothyroidism. MATERIAL AND METHODS: A search of MEDLINE identified 25 studies
      on the association between smoking and thyroid diseases. RESULTS: In Graves'
      disease eight studies were available showing an odds ratio (OR) of 3.30 (95%
      confidence interval (CI): 2.09-5.22) in current smokers compared with never
      smokers. In ex-smokers there was no significant excess risk of Graves' disease
      (OR=1.41, 95% CI: 0.77-2.58). The OR associated with ever smoking in Graves'
      ophthalmopathy (4.40, 95% CI: 2.88-6.73, six studies) was significantly higher
      than in Graves' disease (1.90, 95% CI: 1.42-2.55, two-sided P-value <0.01). Ever
      smoking was not associated with toxic nodular goitre (OR=1.27, 95% CI: 0.69-2.33,
      three studies), while there was an increased risk of non-toxic goitre in smokers
      if men were excluded (OR=1.29, 95% CI: 1.01-1.65, eight studies). The risk
      associated with smoking was significantly lower in men than in women for both
      Graves' disease and non-toxic goitre. Hashimoto's thyroiditis and post-partum
      thyroid dysfunction were also associated with smoking while the association with
      hypothyroidism did not reach statistical significance. CONCLUSIONS: Cessation of
      smoking seems associated with a lower risk of Graves' disease than current
      smoking. Smoking increases the risk of Graves' ophthalmopathy beyond the risk
      associated with Graves' disease alone. Smoking cessation may lead to a decrease
      in morbidity from Graves' disease, especially in women.

PMID- 11834424
TI  - Demonstration of reduced in vivo surface expression of activating mutant
      thyrotrophin receptors in thyroid sections.
AB  - OBJECTIVE: Thyroid function and growth are controlled by TSH. Hyperthyroidism can
      be due to Graves' Disease (GD), in which thyroid-stimulating antibodies mimic
      TSH, or gain-of-function mutations in the TSH receptor (TSHR). These activating
      mutations have poor surface expression when assessed in non-thyroidal cells in
      vitro but nothing is known of their in vivo behaviour. Several TSHR antibodies
      have been produced but none has been applied to thyroid paraffin sections. This
      study aimed to develop a technique suitable for use on paraffin sections and
      apply it to investigate TSHR expression in thyroids harbouring activating TSHR
      germline mutations compared with normal and GD thyroids. DESIGN AND METHODS:
      Immunocytochemistry coupled with antigen retrieval, using a spectrum of
      antibodies to the TSHR, was applied to paraffin sections of GD thyroid tissue.
      Subsequently, TSHR immunoreactivity was examined in three normal thyroids, three
      patients with GD and three patients with familial hyperthyroidism, due to
      different gain-of-function TSHR germline mutations, using the optimised protocol.
      RESULTS: Two antibodies, A10 and T3-495, to the extracellular domain (ECD) and
      membrane spanning region (MSR) of the TSHR respectively, produced specific
      basolateral staining of thyroid follicular cells. In normal and GD thyroids,
      basolateral staining with T3-495 was generally more intense than with A10,
      suggesting a possible surfeit of MSR over ECD. Graves' Disease thyroids have more
      abundant TSHR than normal glands. In contrast, thyroids harbouring gain-of
      function mutations have the lowest expression in vivo, mirroring in vitro
      findings. CONCLUSIONS: The development of an immunocytochemical method applicable
      to paraffin sections has demonstrated that different molecular mechanisms causing
      hyperthyroidism result in the lowest (mutation) and highest (autoimmunity) levels
      of receptor at the thyrocyte surface.

PMID- 11834425
TI  - Use of the 2nd generation TRAK human assay did not improve prediction of relapse
      after antithyroid medical therapy of Graves' disease.
AB  - OBJECTIVE: Antithyroid drug treatment (ATD) is used world-wide in the treatment
      of thyrotoxicosis in patients with Graves' disease (GD). The main problem is a
      relapse rate of 30 to 50% within 2 years after the treatment has stopped. The
      measurement of thyrotropin receptor antibodies (TRAb) in serum has been used to
      confirm the diagnosis of GD in selected patients with a diagnostic specificity of
      70 to 90%. However, in predicting the recurrence of thyrotoxicosis after
      discontinuing ATD it has been of little value. The aim of this study was to
      evaluate the ability of TRAb measured by the more sensitive recombinant human TSH
      receptor method to predict risk of recurrence of GD after discontinuing ATD.
      MATERIALS, PATIENTS AND METHODS: One hundred and twenty nine patients with newly
      diagnosed GD were included. Of these, 58 had relapse of hyperthyroidism in a
      follow-up of at least 11 months (median 18 months, range 11-49) after
      discontinuing ATD. In 122 Graves' patients TRAb were measured at the time of
      diagnosis and in all patients when discontinuing ATD by a competitive
      radioreceptor assay using recombinant human TSH receptors (TRAK human assay).
      RESULTS: We found an increased diagnostic specificity (99%) compared with the old
      TRAK porcine assay. The predictive values of a positive and negative test in
      relation to the prediction of a relapse of GD were found to be only 55% and 62%
      respectively when using a cut-off level of 1.5 IU/l, and the predictive value of
      a positive test decreased to 49% and of a negative test to 60% at a lower cut-off
      limit (1 IU/l). CONCLUSION: Our study confirms that the new TRAK human assay had
      a superior diagnostic sensitivity in comparison with the old TRAK porcine assay.
      Despite the higher diagnostic sensitivity of the TRAK human method, we could not
      find any improvement of predictive values for relapse of hyperthyroidism in the
      measurement of TRAb at the end of ATD.

PMID- 11834426
TI  - MRI protocol technique in the optimal therapeutic strategy of non-functioning
      pituitary adenomas.
AB  - OBJECTIVES AND DESIGN: We performed a prospective study using magnetic resonance
      imaging (MRI) at regular post-operative intervals in non-irradiated patients with
      non-functioning pituitary adenomas (NFAs) to assess the frequency of tumoral
      regrowth and recurrences, in order to define the indications of post-operative
      radiotherapy. PATIENTS AND METHODS: Fifty-one patients aged 25--80 years (mean,
      55.6plus minus12.3 years) were included. Post-operative MRIs were performed 3--12
      months (mean, 5.2plus minus1.7 months) after surgery, 6 months later and then,
      every 12--18 months for at least 2 years. The mean post-operative follow-up was
      67.7plus minus31.8 months (range, 24--144 months). RESULTS: In 17 patients (33%,
      group I) no tumoral residue was observed on post-operative MRIs and no tumoral
      recurrence was diagnosed. Tumour regrowth was detected in 13 of the 34 patients
      (38.2%) with post-operative tumoral residue (group II), 7--66 months (mean,
      27.3plus minus17.3 months) after surgery. In this group, Kaplan--Meier analysis
      showed 78.8% recurrence free survival at 2 years and 60.9% at 5 years. Patients
      with tumoral regrowth had higher mean residual tumoral volume than patients
      without any tumoral regrowth in the group II (258plus minus165 vs 163plus
      minus165 mm(3), P=0.05). CONCLUSIONS: We suggest a MRI protocol that includes, a
      4- to 6-, 12- and 24-month post-operative MRI for every patient. When no tumoral
      residue is seen, pituitary radiotherapy is useless. MRI must be repeated 3, 5 and
      10 years after surgery to eliminate late recurrence. The observed frequency of
      tumoral regrowth in patients with tumoral residue does not justify systematic
      post-operative radiotherapy. It should be performed only when tumoral regrowth is
      proved by a yearly MRI survey.

PMID- 11834427
TI  - Bone mineral content and bone metabolism during physiological GH treatment in GH
      deficient adults--an 18-month randomised, placebo-controlled, double blinded
      trial.
AB  - OBJECTIVE: To evaluate the effect of physiological adult growth hormone (GH)
      replacement on bones. DESIGN: Thirty-six prospective severely growth hormone
      deficient (GHD) adults (22 females and 14 males) were randomised to either 18
      months of GH (0.03 mU/kg/day) or placebo treatment. METHODS: Bone mineral density
      and content (BMD, BMC) and body composition were evaluated by dual energy X-ray
      absorptiometry at baseline and after 6, 12 and 18 months. Serum concentrations of
      insulin-like growth factor-I (IGF-I), IGF binding protein 3, osteocalcin,
      carboxyterminal propeptide of type I collagen, carboxyterminal crosslink
      telopeptide of type I collagen, amino-terminal propeptide of type III procollagen
      and urine pyridinolin and deoxypyridinolin were determined. RESULTS: IGF-I levels
      increased from 63.2 microg/l (+/-10.1) to 193.6 (+/- 25.8) microg/l (mean (+/
      s.e.)) (P<0.001 compared with placebo). Markers of bone turnover increased
      significantly from 142% to 227% of baseline values (all P<0.001 compared with
      placebo). Body composition changes were an increase of lean body mass and a
      decrease of fat mass resulting in a reduction of percentage body fat of +/- 1.8
      (+/- 3.8) in the GH-treated group vs an increase of 1.0 (+/-2.9)) in the placebo
      treated group (P=0.002). CONCLUSIONS: No significant difference in BMD or BMC
      between the GH and placebo groups was found after 18 months. At several sites the
      variances of changes from baseline were significantly greater in the GH than in
      the placebo group, indicating an impact of the treatment. From baseline to 6
      months an insignificant reduction of total BMD was seen while an increase of BMD
      was found from 6 to 18 months in the GH group compared with the placebo group.
      This placebo-controlled trial confirmed the longer term open studies on the
      effect on bones in patients with GHD, with an initial overrepresentation of bone
      resorption followed by an increase in BMD which at 18 months had reached baseline
      level.

PMID- 11834428
TI  - The role of endogenous GHRH in arginine-, insulin-, clonidine- and l-dopa-induced
      GH release in normal subjects.
AB  - OBJECTIVE: The role of endogenous GHRH in arginine-, insulin-, clonidine- and l
      dopa-induced GH secretion was studied in man using a GHRH antagonist (GHRH-Ant).
      DESIGN: Ten healthy adult males were studied for serum GH responses to arginine
      or insulin singly, or sequentially 120 min after GHRH injection with or without
      combined administration of GHRH-Ant. Further, GHRH, clonidine or l-dopa were
      sequentially administered to these subjects 120 min after the GHRH injection.
      RESULTS: The combined administration of GHRH-Ant distinctly inhibited the
      arginine- and insulin-induced GH release. When these four agents were
      sequentially administered 120 min after GHRH injection, the GH responses to
      clonidine and l-dopa disappeared completely while clear responses were observed
      to arginine and insulin administration. These responses to arginine and insulin
      were also completely inhibited by the combined administration of GHRH-Ant.
      CONCLUSIONS: These results indicate that clonidine and l-dopa stimulate GH
      secretion mainly through the release of hypothalamic GHRH, and that arginine- and
      insulin-induced hypoglycaemia stimulate GH secretion mainly through the
      inhibition of hypothalamic somatostatin release. However, the presence of
      endogenous hypothalamic GHRH seems to be essential for the maximal stimulation of
      GH release induced by arginine and insulin.

PMID- 11834429
TI  - Ghrelin drives GH secretion during fasting in man.
AB  - OBJECTIVES: In humans, fasting leads to elevated serum GH concentrations.
      Traditionally, changes in hypothalamic GH-releasing hormone and somatostatin
      release are considered as the main mechanisms that induce this elevated GH
      secretion during fasting. Ghrelin is an endogenous ligand of the GH secretagogue
      receptor and is synthesized in the stomach. As ghrelin administration in man
      stimulates GH release, while serum ghrelin concentrations are elevated during
      fasting in man, this increase in ghrelin levels might be another mechanism
      whereby fasting results in stimulation of GH release. DESIGN AND SUBJECTS: In ten
      healthy non-obese males we performed a double-blind placebo-controlled crossover
      study comparing fasting with and fasting without GH receptor blockade. GH,
      ghrelin, insulin, glucose and free fatty acids were assessed. RESULTS: While
      ghrelin levels do not vary considerably in the fed state, fasting rapidly induced
      a diurnal rhythm in ghrelin concentrations. These changes in serum ghrelin
      concentrations during fasting were followed by similar, profound changes in serum
      GH levels. The rapid development of a diurnal ghrelin rhythm could not be
      explained by changes in insulin, glucose, or free fatty acid levels. Compared
      with fasting without pegvisomant, fasting with pegvisomant did not change the
      ghrelin rhythm. CONCLUSIONS: These data indicate that ghrelin is the main driving
      force behind the enhanced GH secretion during fasting.

PMID- 11834430
TI  - Chromosomal imbalances identified by comparative genomic hybridization in
      sporadic parathyroid adenomas.
AB  - OBJECTIVE: To identify chromosomal gains and losses in sporadic parathyroid
      adenomas (PAs). METHODS: Fourteen sporadic PAs were studied by comparative
      genomic hybridization (CGH). RESULTS: The fourteen studied PAs showed chromosomal
      imbalances. All cases except one exhibited two or more abnormalities. Chromosomal
      gains were found in all cases, and three cases (21%) also presented chromosomal
      losses. Genomic amplification was not observed. Chromosome 9 was involved in ten
      cases. Recurrent genetic gain was found on 9p22-24 and on 9q34, each in 6 of 14
      cases (43%). Other recurrent gains included Xq26 in 6 PAs (43%) and 4q21-28 and
      8p22-23, each in 4 of 14 cases (29%). Regions of recurrent genetic loss involved
      whole chromosome 11 and 20q12-13, each in 2 of 14 cases (14%). CONCLUSIONS: Our
      findings show chromosomal imbalances in all sporadic PAs studied by CGH, partly
      confirming previous reports, with the exception that we observed more chromosomal
      gains than losses. Several regions (9p22-24, 9q34, Xq26, 4q21-28, and 8p22-23)
      probably deserve further investigation in order to discard the presence of genes
      involved in parathyroid tumorigenesis.

PMID- 11834432
TI  - Expression and enzymatic activity of the P450c17 gene in human adipose tissue.
AB  - OBJECTIVE: P450 aromatase activity increases with age in adipose tissue.
      Increased oestrogen production has also been observed in obese elderly women, and
      has been related to the pathogenesis of endometrial cancer. Since peripheral
      oestrogen production requires the presence of androgenic metabolites, and a
      recent report from our laboratory showed very low expression levels of P450c17
      mRNA in most postmenopausal ovaries analysed, we hypothesised on the existence of
      an alternative source of androgens. Since steroidogenic enzymes, such as 3beta
      hydroxysteroid dehydrogenase (3beta-HSD) and 17beta-HSD have been described in
      adipose tissue of primates and humans respectively, we aimed to analyse the
      possible expression of the P450c17 gene in adipose tissue, and its enzymatic
      capability. DESIGN: A prospective non-randomised clinical research study.
      METHODS: Subcutaneous abdominal adipose tissue and random pieces of whole normal
      ovaries were collected at surgery from nineteen women undergoing bilateral
      oophorectomy for non-ovarian gynaecological disease. P450c17 mRNA expression
      levels were measured by RT-PCR/Southern blot analysis, and 17alpha-hydroxylase
      enzymatic activity in dispersed cell homogenates was performed by thin-layer
      chromatography, using (14)C-progesterone as a substrate. RESULTS: The study
      provides the first description of 17alpha-hydroxylase activity in adipose tissue
      and the detection of a new form of the P450c17 cDNA containing a 156 bp in-frame
      deletion in the first exon. CONCLUSIONS: The description of 17alpha-hydroxylase
      activity in adipose tissue, together with previously reported enzymatic
      activities such as 3beta-HSD and17beta-HSD, might suggest a local production of
      androgens in this tissue.

PMID- 11834431
TI  - Well-being, mood and calcium homeostasis in patients with hypoparathyroidism
      receiving standard treatment with calcium and vitamin D.
AB  - OBJECTIVE: Standard treatment in hypoparathyroidism consists of calcium and
      vitamin D (or vitamin D analogs) but does not employ replacement of the actual
      missing hormone. Only few studies have evaluated the efficacy of calcium/vitamin
      D treatment in hypoparathyroidism; the impact of chronic hypoparathyroid disease
      on well-being has not been investigated previously. DESIGN: Cross-sectional,
      controlled study in 25 unselected women with postsurgical hypoparathyroidism
      since 6.4plus minus8.0 years (s.d.) on stable treatment with calcium and vitamin
      D (or analogs) and in 25 controls with a history of thyroid surgery but intact
      parathyroid function, who were matched for sex, age and time since surgery.
      METHODS: Assessment of well-being and mood using validated questionnaires (the
      revised version Symptom Checklist 90 (SCL-90-R); the Giessen Complaint List (GBB
      24); and the von Zerssen Symptom List (B-L Zerssen)), serum and urinary
      calcium/phosphorus homeostasis, and in the hypoparathyroid patients also
      screening for secondary disease by kidney ultrasound, ophthalmological split lamp
      examination, and measurement of bone mineral density. RESULTS: Serum calcium was
      in the accepted therapeutic range in the majority of hypoparathyroid patients.
      However, calcium/phosphorus homeostasis as a whole was clearly non-physiological.
      Nephrolithiasis was detected in 2 and cataracts in 11 of 25 hypoparathyroid
      patients. As compared with controls, hypoparathyroid patients had significantly
      higher global complaint scores in GBB-24 (P=0.036), B-L Zerssen (P=0.002) and SCL
      90-R (P=0.020) with predominant increases in the subscale scores for anxiety,
      phobic anxiety and their physical equivalents. CONCLUSIONS: Current standard
      treatment in hypoparathyroidism is not only associated with an altered
      calcium/phosphorus homeostasis but also fails to restore well-being in these
      patients. Future studies need to address the impact of more physiological
      treatment options like parathyroid hormone(1-34) or parathyroid transplantation
      on well-being and mood in these patients.

PMID- 11834433
TI  - Cortisol-binding globulin is important in the interpretation of dynamic tests of
      the hypothalamic--pituitary--adrenal axis.
AB  - OBJECTIVE: Assessment of the hypothalamic--pituitary--adrenal (HPA) axis relies
      on the interpretation of serum (total) cortisol in response to dynamic tests of
      the HPA axis. Most cortisol is bound to cortisol-binding globulin (CBG) and serum
      total cortisol levels are significantly affected by variation in CBG. We
      hypothesised that CBG variation significantly affects interpretation of dynamic
      tests of the HPA axis. DESIGN: We investigated the effect of CBG variation on the
      outcome of the 250 microg short Synacthen test (SST) in 30 healthy adults.
      METHODS: Blood was sampled at time -30, 0 (at which point Synacthen was given)
      and +30 min. CBG and total cortisol were measured at each time-point. Integrity
      of the HPA axis was confirmed by measurement of urine cortisol. RESULTS: We found
      that CBG varied significantly within individuals, falling from 51+/-3.4 to 43 +/
      3.2 microg/ml (P<0.0001) on changing from standing to lying. Total cortisol
      levels strongly correlated with CBG (r=0.88, P<0.0001). Thirteen subjects had a
      +30 min total cortisol <550 nmol/l. In these subjects, the CBG levels at each
      time-point were significantly lower compared with subjects who had a +30 min
      total cortisol of >550 nmol/l (P<0.05). To correct for variation in CBG we
      calculated the total cortisol:CBG ratio and found no significant difference in
      the +30 min ratio between these two groups. CONCLUSION: CBG varies significantly
      within and between individuals. This is accompanied by changes in serum total
      cortisol large enough to affect the outcome of an SST and, by implication, other
      tests of the HPA axis.

PMID- 11834434
TI  - Is unilateral adrenalectomy an alternative treatment for ACTH-independent
      macronodular adrenal hyperplasia?: Long-term follow-up of four cases.
AB  - OBJECTIVE: ACTH-independent macronodular adrenal hyperplasia is a rare cause of
      Cushing's syndrome. Bilateral adrenalectomy is considered the treatment of
      choice, but the patient is obliged to receive lifetime steroid replacement
      therapy and is susceptible to adrenal insufficiency crisis. New therapeutic
      alternatives are being proposed as new etiopathological features of the disease
      are known. Unilateral adrenalectomy of the largest gland can be a safe and
      effective alternative, but only short-term follow-up is reported in the
      literature. We present four consecutive patients with ACTH-independent
      macronodular hyperplasia and long-term remission of Cushing's syndrome after
      unilateral adrenalectomy. SUBJECTS: Four consecutive patients (two males and two
      females, mean age 50.3 years) with Cushing's syndrome due to ACTH-independent
      macronodular adrenal hyperplasia underwent unilateral adrenalectomy of the
      largest gland. RESULTS: The weight of the resected glands ranged from 26.8 to 210
      g. Two patients suffered transient post-surgical adrenal insufficiency and had
      steroid replacement therapy for 60 and 14 months respectively. After a mean
      follow-up of 78.8 months (range 30-137 months) all the patients persist without
      any evidence of Cushing's syndrome. Urinary free cortisol and serum cortisol,
      after the adrenal insufficiency stage, have always stayed within their normal
      ranges, but cortisol circadian rhythm and suppressibility after dexamethasone
      have never normalized. No further enlargement of the contralateral gland has been
      documented 62 to 126 months after surgery in three of the four patients.
      CONCLUSIONS: Unilateral adrenalectomy can be an effective and safe alternative
      treatment for ACTH-independent macronodular adrenal hyperplasia, and can achieve
      long-term remission of Cushing's syndrome.

PMID- 11834435
TI  - Inhibitory effect of ghrelin on insulin and pancreatic somatostatin secretion.
AB  - OBJECTIVE: Ghrelin is a 28 amino acid residue peptide identified in both human
      and rat stomach and which acts as an endogenous ligand for the GH secretagogue
      receptor (GHS-R) and stimulates GH release. GHS-Rs are expressed in a number of
      tissues, including the pancreas, and ghrelin-like immunoreactivity is present in
      peripheral plasma, where its levels increase during fasting and decrease after
      food intake. The relationship between nutritional status and circulating ghrelin
      concentrations prompted us to investigate the effect of this peptide on
      pancreatic hormone secretion. METHODS: The study was performed in the isolated
      rat pancreas perfused in situ. Insulin, glucagon and somatostatin were measured
      by radioimmunoassay. RESULTS: Addition of 10 nM ghrelin to the perfusate
      significantly reduced the insulin response to the secretagogues glucose, arginine
      and carbachol, which act on the B-cell via different mechanisms, as well as the
      somatostatin response to arginine. Ghrelin was without effect on the glucagon
      output induced by this amino acid. At a lower concentration (2 nM) ghrelin was
      also found to inhibit glucose-induced insulin release. CONCLUSION: These findings
      support the proposal that the inhibitory effect of ghrelin on insulin release
      constitutes a tonic regulation of the B-cell, contributing to restrain its
      secretory activity in the state of food deprivation. On the other hand, the
      inhibition of pancreatic somatostatin release by ghrelin suggests a blocking
      effect of this hormone on the widely distributed D-cell population.

PMID- 11834436
TI  - Effects of pair-feeding and growth hormone treatment on obese transgenic rats.
AB  - BACKGROUND: It has been shown that GH-deficient subjects tend to have fat
      accumulation. We have produced human GH (hGH) transgenic rats that exhibit low
      circulating hGH levels and hyperphagia. These rats are also characterized by
      severe obesity, hyperinsulinemia and hyperlipidemia. OBJECTIVE: The present study
      was conducted in order to elucidate how excess caloric intake and impaired GH
      secretion account for fat accumulation and metabolic abnormalities in the
      transgenic rats. DESIGN AND METHODS: The transgenic rats were subjected to either
      pair-feeding with non-transgenic controls or hGH treatment from 4 to 12 weeks of
      age, and the effects on fat accumulation and some metabolic parameters were
      assessed. RESULTS: At the age of 12 weeks, body weight and food intake were
      greater in transgenic than in control rats by 10% and 27% respectively. The ratio
      of epididymal white adipose tissue weight to body weight (WAT/BW) was more than
      three times greater in transgenic than in control rats. Although pair-feeding for
      8 weeks decreased body weight, it did not affect the WAT/BW ratio. Treatment with
      hGH affected neither body weight nor food intake, while it reduced the WAT/BW
      ratio by 30%. Serum concentrations of triglyceride, free fatty acid, insulin and
      leptin were all significantly higher in the transgenic than in the control rats.
      Pair-feeding decreased serum triglyceride, insulin and leptin levels, but not
      serum free fatty acid levels. On the other hand, hGH treatment decreased only
      serum leptin concentrations. CONCLUSIONS: These results suggest that severe fat
      accumulation in the transgenic rats mainly resulted from the decreased lipolytic
      action of GH, while metabolic abnormalities mainly resulted from excess caloric
      intake.

PMID- 11834437
TI  - Postnatal endotoxin exposure results in increased insulin sensitivity and altered
      activity of neuroendocrine axes in adult female rats.
AB  - OBJECTIVES: Severe postnatal infection leads to a systemic inflammatory response
      with release of cytokines and glucocorticoids, representing a stressful event for
      the newborn child. The purpose of this study was to mimic this situation and to
      study the effects of early postnatal endotoxin exposure of female rat pups on
      metabolic, endocrine and anthropometric variables in adulthood. DESIGN: Female
      pups were given subcutaneous injections of lipopolysaccharides (LPS; Salmonella
      enteriditis, 0.05 mg/kg) or vehicle 3 and 5 days after birth. RESULTS: Six hours
      after injection, LPS-treated rats had higher corticosterone levels than controls.
      As adults, LPS-exposed female rats showed increased insulin sensitivity (P<0.05),
      measured with the hyperinsulinemic euglycemic clamp (5 mU/kg per min). They
      exhibited a higher locomotor activity (P<0.05) and increased skeletal muscle mass
      in comparison with controls (P<0.05). Basal ACTH and corticosterone levels in LPS
      treated rats were elevated (P<0.05), as were corticosterone levels after exposure
      to a novel environment stress (P<0.05). The adrenals were morphologically changed
      and enlarged (P<0.05) in LPS-exposed rats at 11 weeks of age, and a higher
      density of hypothalamic but not hippocampal glucocorticoid receptor protein was
      found in the LPS-treated rats (P<0.05). Furthermore, circulating progesterone
      levels were lower (P<0.05) and testosterone tended to be higher. CONCLUSION: The
      results indicate that postnatal exposure to LPS leads to increased insulin
      sensitivity in the adult female rat. In addition, LPS-treated rats showed changes
      in the regulation of hypothalamic-pituitary-adrenal and hypothalamic-pituitary
      gonadal axes. This study suggests that postnatal exposure to an endotoxin such as
      LPS can induce specific programming of neuroendocrine regulation, with long-term
      consequences in adult life.

PMID- 11834438
TI  - Effects of leptin on gonadotropin secretion in juvenile female rat pituitary
      cells.
AB  - OBJECTIVE: Leptin is an adipocyte-derived hormone, which is the product of the
      obese gene and it is thought to play important roles in pubertal development and
      maintenance of reproductive function in the female. In a study using adult male
      or female rats, it was found that leptin stimulated the secretion of gonadotropin
      directly from the pituitary in a dose-related manner. However, there is no study
      in juvenile female rats before puberty. METHODS: In this study, we cultured
      pituitary cells from 4-, 6- and 8-week-old female Wistar rats with leptin (0-10(
      7)mol/l) and gonadotropin-releasing hormone (GnRH) (0 or 10(-8) mol/l). Basal or
      GnRH-stimulated secretion of luteinizing hormone (LH) and follicle-stimulating
      hormone (FSH), and their synthesis within cells were determined by
      radioimmunoassay (RIA). RESULTS: Leptin induced bell-shaped dose--response curves
      of basal LH and FSH secretion from cultured cells of every age-group of rats
      studied. The most effective concentration of leptin on the basal secretion of LH
      and FSH from 6- and 8-week-old cultured pituitary cells was 10(-10) mol/l. This
      leptin concentration was consistent with circulating physiological serum leptin
      levels at each age. As for juvenile 4-week-old pituitary cells, the most
      effective concentration was 10(-11) mol/l which was lower than that of 6- and 8
      week-old rats. It was consistent with the circulating serum leptin levels of 4
      week-old rats. Also, the synthesis and the GnRH-stimulated secretion of LH and
      FSH were effectively controlled by leptin at concentrations similar to the serum
      leptin levels of given ages. CONCLUSIONS: Leptin induced pituitary cells to
      synthesize and secrete both LH and FSH regardless of the presence or absence of
      GnRH. The concentration of leptin that induced the greatest synthesis and
      secretion of gonadotropins from pituitary cells changed around the pubertal
      period. The most effective leptin concentrations in each experiment were similar
      to the physiological serum leptin level at each animal age. These results
      indicate that leptin stimulates gonadotrophs not only in the pubertal and the
      mature period but also in the juvenile period before puberty. It is also
      conceivable that leptin may modulate the sensitivity of gonadotrophs until the
      appearance of GnRH stimulation, and may be the factor that brings about puberty
      onset.

PMID- 11834439
TI  - Interactive effects of growth hormone and oestrogen on vascular responses in
      hypophysectomised female rats.
AB  - OBJECTIVE: Growth hormone (GH) and oestrogen (E(2)) are associated with
      beneficial effects on the cardiovascular system and it is therefore of great
      interest to study their interactive effects on haemodynamics and vascular
      function. DESIGN AND METHODS: Female hypophysectomised (Hx) rats were treated for
      seven days with GH, E(2) or a combination of the hormones. Systolic blood
      pressure (SBP), heart rate (HR) and plasma insulin-like growth factor-I (IGF-I)
      were measured. Contractile properties and endothelial function were studied in
      isolated resistance arteries using the wire-myograph technique. RESULTS:
      Hypophysectomy, per se, caused a fall in SBP and HR, while vascular adrenergic
      reactivity (sensitivity to applied noradrenaline) was enhanced. Impaired
      acetylcholine-induced relaxation and basal release of nitric oxide, suggests
      endothelial dysfunction after Hx. After supplementation with GH, SBP remained low
      while HR increased towards the control level. GH increased plasma IGF-I, but had
      no effect on vascular contractility or endothelial responses. E(2) replacement
      resulted in blunted plasma IGF-I, while the vascular adrenergic and serotonergic
      responses were reinforced. Endothelial function was not improved after E(2)
      treatment. When GH and E(2) were given in combination, the GH-induced increase in
      body weight, plasma IGF-I levels and HR were counteracted by E(2). Moreover, the
      anticipated reinforcement of the vascular serotonergic response by E(2) was
      reduced. Neither E(2) nor GH+E(2) affected SBP. CONCLUSIONS: The results suggest
      that GH and E(2) might have interactive effects on haemodynamic and metabolic
      parameters, but not on the contractility or endothelial function of resistance
      arteries, in Hx female rats.

PMID- 11834440
TI  - Growth factor expression and function in the human and mouse preimplantation
      embryo.
AB  - There is increasing evidence that even before implantation, human development is
      regulated by embryonically and maternally derived growth factors. Studies in
      other mammalian species have shown that growth factors and their receptors are
      expressed by the preimplantation embryo and the reproductive tract. Furthermore,
      a number of growth factors have been shown to affect rate of embryo development,
      the proportion of embryos developing to the blastocyst stage, blastocyst cell
      number, metabolism and apoptosis. Growth factor ligands and receptors are also
      expressed in human embryos and the maternal reproductive tract, and
      supplementation of culture medium with exogenous growth factors affects cell
      fate, development and metabolism of human embryos in vitro. Autocrine, paracrine
      and endocrine pathways that may operate within the embryo and between the embryo
      and the reproductive tract before implantation are proposed.

PMID- 11834441
TI  - The influence of maternal size on placental, fetal and postnatal growth in the
      horse. II. Endocrinology of pregnancy.
AB  - Within-breed artificial insemination and between-breed embryo transfer were
      carried out in small pony (P) and large Thoroughbred (Tb) mares to create 4 types
      of horse pregnancy in which the fetus experienced spatial and nutritional
      deprivation (Tb-in-P; n=8), luxury (P-in-Tb; n=7) or normality (Tb-in-Tb; n=7 and
      P-in-P; n=7) in utero. Measurement of equine chorionic gonadotrophin (eCG), total
      conjugated oestrogens and progestagen concentrations in serial peripheral serum
      samples recovered from all the mares throughout gestation showed that the amount
      of eCG produced during the first half of gestation was dependent upon the breed
      of the mare rather than the breed of the fetus being carried. In contrast, the
      mean total amounts of oestrogens produced, as measured by area under the curve,
      were significantly greater (P=0.003) in the two types of pregnancy in which a
      Thoroughbred fetus was being carried (Tb-in-Tb and Tb-in-P) than those in which a
      pony fetus was gestated (P-in-P and P-in-Tb); the evidence suggests that the Tb
      fetus may have larger gonads than the P fetus and thereby secrete more C-19
      precursor steroids for aromatisation to oestrogens by the placenta. In the final
      weeks of pregnancy mean plasma progestagen concentrations rose much earlier, and
      to significantly higher levels (P<0.001), in the Tb-in-P than in the P-in-Tb
      pregnancies, thereby reflecting the increased fetal stress in the former causing
      premature maturation of the fetal adrenal gland. This, in turn, resulted in
      increased secretion of pregnenolone by the adrenal cortex for conversion to
      progestagens by the placenta.

PMID- 11834442
TI  - Potential role of activin A in follicular development during the second half of
      pregnancy in the golden hamster: utero-placental source of activin A.
AB  - Numerous antral follicles develop during the second half of pregnancy in the
      golden hamster. However, mechanisms regulating follicular development during this
      period are unknown. Because inhibin and activin are related to follicular
      development, these hormones were studied to gain insight into any potential roles
      in follicular development. Plasma inhibin A and B suddenly increased from day 8
      of pregnancy, reached peak levels on day 10 and gradually declined to term.
      Plasma activin A gradually increased from day 8 to day 15 of pregnancy, and this
      was followed by an abrupt decrease at day one of lactation. Ovariectomy on day 12
      of pregnancy rapidly reduced plasma inhibin A and B, but not activin A levels.
      Hysterectomy or placentectomy on day 12 of pregnancy caused an abrupt decrease in
      the levels of plasma activin A and FSH, but not inhibin A and B at 6 h after
      surgery. Hysterectomy also induced atresia of large antral follicles at 24 h
      after surgery. These results indicate that antral follicles are the main source
      of circulating inhibin A and B, whereas uteri and placentae are the main source
      of circulating activin A. These results suggest that increased levels of activin
      A may be involved in folliculogenesis in the ovary during the second half of
      pregnancy in the golden hamster.

PMID- 11834443
TI  - Regulation by endogenous opioids of suckling-induced prolactin secretion in
      pregnant and lactating rats: role of ovarian steroids.
AB  - Evidence suggests that endogenous opioid peptides are implicated in the suckling
      induced prolactin rise. We explored the role of the opioid system and the
      participation of ovarian hormones in the regulation of prolactin induced by the
      suckling stimulus at the end of pregnancy in rats with developed maternal
      behavior, and during lactation. Suckling for 24 h induced a significant increase
      in serum prolactin on day 19 of pregnancy, which was increased more than three
      times when naloxone (2 mg/kg s.c.) or mifepristone (2 mg/kg) was administered.
      The combination of naloxone and mifepristone did not increase serum prolactin
      more than either compound alone. Administration of tamoxifen (500 microg/kg
      orally) on days 14 and 15 of pregnancy completely abolished the effect of
      naloxone, indicating a role for estrogens in establishing this inhibitory role of
      opioids. To examine the participation of the opioid system during lactation, we
      used groups of rats on days 1, 3, 5, 12 and 19 postpartum either (i) isolated
      from the pups for 4 h, or (ii) isolated from the pups for 3.5 h and reunited with
      them and suckled for 30 min. Naloxone, given just before replacing the pups,
      prevented the increase in serum prolactin levels observed in the suckled group of
      rats but had no effect on the basal levels of the isolated rats. To examine
      whether the participation of the opioid system in the release of prolactin is
      dependent on the variation of progesterone levels, rats on day 20 of pregnancy
      were implanted with two cannulae containing progesterone (that blocked postpartum
      ovulation) or cholesterol, and cesarean surgery was performed on day 21. To
      maintain lactation, pups (1-3 days old) were replaced every 24 h, and 4 days
      after the cesarean eight pups were placed in the cage at 1800 h to maintain a
      strong suckling stimulus during the following 24 h. Naloxone administration
      significantly reduced serum prolactin levels in control (cholesterol) rats but
      progesterone implants prevented the inhibitory effect of naloxone and this effect
      was not modified by treatment with estrogen. These results indicate that the
      opioid system modulates suckling-induced prolactin secretion, passing from an
      inhibitory action before delivery to a stimulatory action during lactation. This
      regulatory shift seems to be dependent on the fall in progesterone concentration
      at the end of pregnancy and the subsequent increase after the postpartum
      ovulation and luteal phase.

PMID- 11834444
TI  - An investigation of the effect of the prostaglandin EP2 receptor agonist,
      butaprost, on the human isolated myometrium from pregnant and non-pregnant women.
AB  - The aim of this study was to compare the effect of two known spasmogens, oxytocin
      and the stable thromboxane receptor mimetic, U46619, on human myometrium treated
      with the prostaglandin E receptor (EP2) agonist, butaprost (selective for the EP2
      receptor). Strips of myometrium from pregnant and non-pregnant donors were set up
      in a superfusion apparatus. Butaprost was administered as a bolus dose and via
      infusion. During the infusion of 10(-6) M butaprost, spasmogens were administered
      as bolus doses. Butaprost caused dose-related inhibition of myometrial activity
      when administered as a bolus dose (3-100 nmol) and concentration-dependent
      inhibition during infusion studies (10(-8)-10(-5 )M). Butaprost (10(-6 )M)
      attenuated the response to U46619 (0.l-10 nmol) in pregnant myometrium, but this
      difference was not statistically significant. Responses of pregnant myometrium to
      oxytocin (0.01-0.1 nmol) were significantly attenuated (P<0.05) in the presence
      of butaprost (10(-6)M). Butaprost physiologically antagonised the oxytocin
      response, possibly by increasing intracellular cAMP levels. This antagonism was
      much more marked than that seen with butaprost and U46619. It is unclear why
      these two types of antagonism differ and this effect is currently being
      investigated further using other prostanoid and non-prostanoid agents.

PMID- 11834446
TI  - Urocortin increases the expression of heat shock protein 90 in rat cardiac
      myocytes in a MEK1/2-dependent manner.
AB  - We have previously demonstrated that urocortin protects cultured cardiac myocytes
      from ischaemic and reoxygenation injury and decreases the infarct size in the rat
      heart exposed to regional ischaemia and reperfusion. Urocortin-mediated
      cardioprotection is via activation of the mitogen-activated protein kinase (MAP
      kinase, MEK1/2) pathway. In addition, it is well documented that heat shock
      protein (hsp) 70 and hsp90 are cardioprotective against lethal stress. In this
      study we show, for the first time, that urocortin induces the expression of hsp90
      but not hsp70 in primary cultures of rat neonatal cardiac myocytes. Levels of
      hsp90 protein increase by 1.5-fold over untreated cells within 10 min of
      urocortin treatment and are sustained for 24 h with a maximal increase of 2.5
      fold at 60 min (P<0.05 at all time points). The increase in hsp90 expression by
      urocortin was not inhibited by actinomycin D, and urocortin failed to increase
      hsp90 promoter activity. Urocortin induction of hsp90 was inhibited by the MEK1/2
      inhibitor PD98059 (P<0.001) and by cycloheximide, and both inhibitors abrogate
      urocortin-mediated cardioprotection (P<0.05 for cycloheximide, P<0.001 for
      PD98059). Hence, MEK1/2 and protein synthesis are involved in the
      cardioprotective effect of urocortin against hypoxic-mediated cell death,
      possibly due to an increase in expression of hsp90 protein. This is the first
      report of heat shock protein induction by urocortin or any other member of the
      corticotrophin-releasing hormone family.

PMID- 11834445
TI  - Mechanism of prostaglandin E2-stimulated heat shock protein 27 induction in
      osteoblast-like MC3T3-E1 cells.
AB  - We investigated the effect of prostaglandin E2 (PGE2) on the induction of heat
      shock protein 27 (HSP27) and HSP70, and the mechanism behind the induction in
      osteoblast-like MC3T3-E1 cells. PGE2 time-dependently increased the level of
      HSP27 without affecting the level of HSP70. PGE2 stimulated the accumulation of
      HSP27 dose-dependently in the range between 10 nM and 10 microM. PGE2 stimulated
      the increase in the level of the mRNA for HSP27. Staurosporine and calphostin C,
      inhibitors of protein kinase C (PKC), suppressed the PGE2-induced HSP27
      accumulation. The effect of PGE2 on HSP27 accumulation was reduced in the PKC
      down-regulated cells. BAPTA/AM, a chelator of intracellular Ca2+, or TMB-8, an
      inhibitor of intracellular Ca2+ mobilization, reduced the accumulation of HSP27
      induced by PGE2. Dibutyryl cAMP had little effect on the basal level of HSP27.
      PGE2 induced the phosphorylation of both p44/p42 mitogen-activated protein (MAP)
      kinase and p38 MAP kinase. PD98059 and U-0126, inhibitors of the upstream kinase
      of p44/p42 MAP kinase, reduced the accumulation of HSP27 induced by PGE2.
      SB203580, a specific inhibitor of p38 MAP kinase, suppressed the HSP27
      accumulation induced by PGE2. U-73122, an inhibitor of phospholipase C, and
      calphostin C reduced the PGE2-induced phosphorylation of both p44/p42 MAP kinase
      and p38 MAP kinase. These results indicate that PGE2 stimulates the induction of
      HSP27 through PKC-dependent activations of both p44/p42 MAP kinase and p38 MAP
      kinase in osteoblasts.

PMID- 11834447
TI  - Failure of steroid regulation of the MMTV promoter in a small cell lung cancer
      cell line is caused by a DNA sequence flanking the glucocorticoid response
      element.
AB  - We have previously described a panel of human small cell lung carcinoma (SCLC)
      cell lines that have profound glucocorticoid resistance, resulting from various
      molecular defects in glucocorticoid signalling. However, in one SCLC cell line,
      CORL103, the cause of the resistance is unknown. These cells are refractory to
      dexamethasone stimulation of MMTV even when exogenous wild-type glucocorticoid
      receptor (GR) is co-transfected. This is in contrast to cell lines DMS79 and
      CORL24 where resistance is overcome by transfection of the wild-type receptor.
      Sequencing of the GR from CORL103 cells revealed two point mutations, but neither
      of these induced dominant negative activity. Steroid hormone resistance extended
      to mineralocorticoid and progesterone receptor (MR, PR) activation of MMTV-luc,
      whereas oestrogen and thyroid hormone receptor transactivation were normal. A
      simpler reporter, TAT3-luc, containing three copies of the tyrosine
      aminotransferase glucocorticoid response element (GRE), was responsive when
      transfected into CORL103 cells with GR, MR and PR expression vectors and
      activated with their respective ligands. Similarly, pHH-luc and pAH-luc
      (truncated MMTV variants containing the GRE region, both derived from a different
      strain of MMTV), were effectively transactivated with dexamethasone. This
      suggests that the minor changes in the flanking sequence of the MMTV promoter are
      critically important in determining steroid responsiveness in CORL103 cells. We
      propose that minor differences in MMTV may determine recruitment of co-factors,
      which destabilise GR binding to the MMTV GREs. These findings represent a new,
      selective, model of glucocorticoid resistance that may explain specific cell and
      target gene differences in glucocorticoid sensitivity.

PMID- 11834448
TI  - Effects of glucagon-like peptide-1(7-36) amide on neurohypophysial and
      cardiovascular functions under hypo- or normotensive hypovolaemia in the rat.
AB  - To date, glucagon-like peptide 1(7-36) amide (tGLP-1) has been found to affect
      the neurohypophysial and cardiovascular functions in normotensive and
      normovolaemic rats. The aim of the present study was to investigate possible
      effects of tGLP-1 on the mean arterial blood pressure and the release of
      vasopressin and oxytocin under conditions of blood volume depletion in the rat.
      In the first series of experiments, the animals were injected i.p. with either
      0.15 M saline or 30% polyethylene glycol (PEG). PEG caused an 18% reduction of
      blood volume 1 h after injection. No significant changes in the mean arterial
      blood pressure were found in either normo- or hypovolaemic rats during the
      experiment. tGLP-1 injected i.c.v. at a dose of 1 microg/5 microl 1 h after the
      i.p. injection increased similarly the arterial blood pressure in normo- and
      hypovolaemic rats. The plasma vasopressin/oxytocin concentrations were markedly
      elevated in hypovolaemic animals and tGLP-1 further augmented the release of both
      hormones. In the second study, hypovolaemia was induced by double blood
      withdrawal. The haemorrhage resulted in a marked decrease of the mean arterial
      blood pressure and in the elevated plasma vasopressin/oxytocin concentrations.
      tGLP-1 injected immediately after the second blood withdrawal increased the
      arterial blood pressure. In parallel, tGLP-1 enhanced significantly vasopressin
      and oxytocin secretion when compared with haemorrhaged, saline-injected rats. The
      results of this study indicate that tGLP-1 may affect the arterial blood pressure
      and the secretion of neurohypophysial hormones under pathological conditions
      brought about by blood volume depletion.

PMID- 11834449
TI  - A detailed study of the L2beta long-loop region of human chorionic gonadotrophin
      suggests it to be spatially close to, but not part of, the receptor-binding site.
AB  - An in-depth study of the L2beta long-loop region of human chorionic gonadotrophin
      (hCG), earlier identified to be a conformational bioneutralization epitope and
      receptor-binding site of the hormone, was carried out. The linear 38-57 hCGbeta
      peptide and the corresponding cyclic disulphide peptide were synthesized and
      antipeptide antibodies developed. Binding studies with antibodies to the linear
      peptide, and with hCGbeta, hCG and human LH suggest that part of the region is
      buried at the alpha/beta interface and part exposed in hCG. Observation of the
      surface exposure of residues 47-53 from the crystal structure of hCG was
      confirmed by epitope mapping studies of the region. The region is not unique to
      hCG as a majority of the antibodies to both the linear and cyclic peptides did
      not exhibit the required specificity. Competitive inhibition studies with the
      linear and cyclic peptides failed to show inhibition of radiolabelled hCG binding
      to its receptors. However, both the antipeptide antibodies were able to
      bioneutralize the hormone in an in vivo assay. Taken together, these results seem
      to indicate that the L2beta long-loop region is not a receptor-binding site of
      hCG but spatially close to it.

PMID- 11834450
TI  - Structurally distinct membrane-associated and soluble forms of GH-binding protein
      in the mouse.
AB  - It has previously been shown that the large increase in GH-binding capacity of
      mouse liver microsomes during pregnancy is due largely to an increase in the
      amount of GH-binding protein (GHBP), with a more modest increase in GH receptor
      (GHR). Here we show that mouse liver GHBP is predominantly present as a membrane
      associated protein structurally distinct from the soluble form of GHBP present in
      serum. Liver GHBP is associated with both intracellular membranes and the plasma
      membrane. Membrane-associated GHBP and soluble GHBP appear to be identical
      polypeptides distinguished by the addition of different N-glycans to asparagine
      residues. The pattern of release of GHBP from membranes by various treatments
      indicates that GHBP associates with membranes through noncovalent interactions
      with one or more membrane protein, but not with GHR. Covalent crosslinking
      provides evidence for several GHBP-associated membrane polypeptides, with
      molecular masses ranging from 58 kDa to over 200 kDa. These studies in the mouse
      and similar studies in the rat suggest that GHBP is an important cell-surface
      receptor for GH in the liver of these species. We postulate that an arginine
      glycine-aspartic acid sequence found on rat and mouse GHBP but absent in other
      species is responsible for the association of GHBP with the plasma membrane by
      binding to one or more integrins on the surface of liver cells.

PMID- 11834451
TI  - Hyperglycemia induces insulin resistance on angiotensinogen gene expression in
      diabetic rat kidney proximal tubular cells.
AB  - Clinical and animal studies have shown that treatment with angiotensin-converting
      enzyme (ACE) inhibitors or angiotensin II (Ang II) receptor antagonists slows the
      progression of nephropathy in diabetes, indicating that Ang II plays an important
      role in its development. We have reported previously that insulin inhibits the
      stimulatory effect of high glucose levels on angiotensinogen (ANG) gene
      expression in rat immortalized renal proximal tubular cells (IRPTCs) via the
      mitogen-activated protein kinase (p44/42 MAPK) signal transduction pathway. We
      hypothesize that the suppressive action of insulin on ANG gene expression might
      be attenuated in renal proximal tubular cells (RPTCs) of rats with established
      diabetes. Two groups of male adult Wistar rats were studied: controls and
      streptozotocin (STZ)-induced diabetic rats at 2, 4, 8 and 12 weeks post-STZ
      administration. Kidney proximal tubules were isolated and cultured in either
      normal glucose (i.e. 5 mM) or high glucose (i.e. 25 mM) medium to determine the
      inhibitory effect of insulin on ANG gene expression. Immunoreactive rat ANG (IR
      rANG) in culture media and cellular ANG mRNA were measured by a specific
      radioimmunoassay and reverse transcription-polymerase chain reaction assay
      respectively. Activation of the p44/42 MAPK signal transduction pathway in rat
      RPTCs was evaluated by p44/42 MAPK phosphorylation employing a PhosphoPlus p44/42
      MAPK antibody kit. Insulin (10(-7) M) inhibited the stimulatory effect of high
      glucose levels on IR-rANG secretion and ANG gene expression and increased p44/42
      MAPK phosphorylation in normal rat RPTCs. In contrast, it failed to affect these
      parameters in diabetic rat RPTCs. In conclusion, our studies demonstrate that
      hyperglycaemia induces insulin resistance on ANG gene expression in diabetic rat
      RPTCs by altering the MAPK signal transduction pathway.

PMID- 11834452
TI  - Time-dependent potentiation of the beta-cell is a Ca2+-independent phenomenon.
AB  - When isolated rat pancreatic islets are treated with 16.7 mM glucose, a time
      dependent potentiation (TDP) of insulin release occurs that can be detected by
      subsequent treatment with 50 mM KCl. It has been thought that TDP by glucose is a
      Ca2+-dependent phenomenon and only occurs when exposure to glucose is carried out
      in the presence of Ca2+. In contrast to this, we now demonstrate TDP under
      stringent Ca2+-free conditions (Ca2+-free buffer containing 1 mM EGTA). In fact,
      under these Ca2+-free conditions glucose caused an even stronger TDP than in the
      presence of Ca2+. TDP induced by glucose in the absence of extracellular Ca2+ was
      unaffected by inhibitors of protein kinase C (PKC). However, cerulenin or
      tunicamycin, two inhibitors of protein acylation, eradicated TDP without
      affecting glucose metabolism. The TDP by glucose was not associated with an
      increase in the cytosolic free Ca2+ concentration ([Ca2+]i) during subsequent
      treatment with high K+. Exposure of islets to forskolin under Ca(2+)-free
      conditions did not cause TDP despite a large increase in the cellular cAMP
      levels. In conclusion, glucose alone induces TDP under stringent Ca2+-free
      conditions when [Ca2+]i was significantly lowered. Protein acylation is
      implicated in the underlying mechanism of TDP.

PMID- 11834453
TI  - Preservation of active incretin hormones by inhibition of dipeptidyl peptidase IV
      suppresses meal-induced incretin secretion in dogs.
AB  - The incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent
      insulinotropic polypeptide (GIP) are degraded by dipeptidyl peptidase IV (DPP
      IV), thereby losing insulinotropic activity. DPP IV inhibition reduces exogenous
      GLP-1 degradation, but the extent of endogenous incretin protection has not been
      fully assessed, largely because suitable assays which distinguish between intact
      and degraded peptides have been unavailable. Using newly developed assays for
      intact GLP-1 and GIP, the effect of DPP IV inhibition on incretin hormone
      metabolism was examined. Conscious dogs were given NVP-DPP728, a specific DPP IV
      inhibitor, at a dose that inhibited over 90% of plasma DPP IV for the first 90
      min following treatment. Total and intact incretin concentrations increased
      (P<0.0001) following a mixed meal, but on control days (vehicle infusion), intact
      peptide concentrations were lower (P<0.01) than total peptide concentrations
      (22.6 +/- 1.2% intact GIP; 10.1 +/- 0.4% intact GLP-1). Following inhibitor
      treatment, the proportion of intact peptide increased (92.5 +/- 4.3% intact GIP,
      P<0.0001; 99.0 +/- 22.6% intact GLP-1, P<0.02). Active (intact) incretins
      increased after NVP-DPP728 (from 4797 +/- 364 to 10 649 +/- 106 pM x min for GIP,
      P<0.03; from 646 +/- 134 to 2822 +/- 528 pM x m in for GLP-1, P<0.05). In
      contrast, total incretins fell (from 21 632 +/- 654 to 12 084 +/- 1723 pM x min
      for GIP, P<0.002; from 5145 +/- 677 to 3060 +/- 601 pM x min for GLP-1, P<0.05).
      Plasma glucose, insulin and glucagon concentrations were unaltered by the
      inhibitor. We have concluded that DPP IV inhibition with NVP-DPP728 prevents N
      terminal degradation of endogenous incretins in vivo, resulting in increased
      plasma concentrations of intact, biologically active GIP and GLP-1. Total
      incretin secretion was reduced by DPP IV inhibition, suggesting the possibility
      of a feedback mechanism.

PMID- 11834454
TI  - Influence of hypothyroidism on circulating concentrations and liver expression of
      IGF-binding proteins mRNA from neonatal and adult rats.
AB  - The aim of this work was to study the influence of the endocrine balance between
      thyroid hormones, insulin and growth hormone (GH) on the regulation of insulin
      like growth factor binding proteins (IGFBPs), complementing a study previously
      reported for insulin-like growth factors (IGFs) in similar populations. Serum
      concentrations of IGFBPs-1 to -3 were assayed by Western ligand blot and their
      mRNA expression in the liver assayed by RNase protection assay in the hypothyroid
      populations: thyroidectomized and mercapto-1-methylimidazole (MMI)-treated
      neonates, and thyroidectomized adult rats at different periods after
      thyroidectomy. Serum concentrations of insulin, GH and IGF-I were increased in
      thyroidectomized neonates and decreased in the other populations. IGFBPs-1 and -2
      increased 79% and 50% respectively in thyroidectomized neonatal rats compared
      with control at 15 days after thyroidectomy, whereas only IGFBP-2 increased (87%)
      in MMI-treated neonates, which had low serum insulin and GH compared with control
      on the same days. In thyroidectomized adult rats, IGFBPs-1 and -2 decreased 60%
      compared with controls on all days studied. Furthermore, when streptozotocin was
      administered to thyroidectomized neonates and insulin was given to
      thyroidectomized adult rats to restore insulin to control values in both groups,
      a differential regulation was found for IGFBPs-1 and -2. The transcriptionally
      induced decrease in IGFBP-3 (20-25% compared with control in neonates and 50% in
      adult rats), however, seemed to be regulated by GH and IGF-I. The similarity of
      changes in IGFBPs found in hypothyroid, undernourished and streptozotocin-induced
      diabetic neonatal rats suggests that the regulatory effect of insulin or GH on
      the IGFBPs requires the reduced biologically active thyroid hormone that is found
      in these three populations.

PMID- 11834455
TI  - Cell necrosis and apoptosis are differentially regulated during goitre
      development and iodine-induced involution.
AB  - Necrosis and apoptosis coexist in the thyroid during goitre development and
      involution, but little is known about their respective causes. To test the
      possible role of free radicals, we analysed separately necrosis and apoptosis in
      male Wistar rats with depressed or normal antioxidant protection. Vitamin E
      deficient and -sufficient rats were made goitrous with perchlorate in drinking
      water; involution was induced by repeated injection of NaI, without or with
      methimazole. Increase of thyroid malondialdehyde concentration and decrease of
      glutathione peroxidase activity confirmed the depressed antioxidant protection in
      vitamin E-deficient rats. Plasma thyroxine and TSH levels were not modified.
      Necrosis (swollen cells) and apoptosis (pyknotic cells) were quantified on
      histological sections. In vitamin E-sufficient rats, dead cells were very rare in
      control thyroids, increased 3-fold in goitre and still further during involution.
      Necrotic epithelial cells predominated in the goitre and their number declined
      after iodide supplementation, without or with methimazole. In contrast, the
      number of apoptotic cells and the caspase-3 activity were increased in goitre and
      further increased after involution, with two-thirds of pyknotic cells being
      observed in the interstitium. Apoptosis was prevented by methimazole. Vitamin E
      deficiency significantly increased total cell death and epithelial cell necrosis
      and induced the occurrence of much cell debris in the follicular lumen during
      involution, with no modification of the apoptotic reaction. These results show
      that the type of cell death is differentially regulated during goitre development
      and involution: necrosis is related to the oxidative status of the cells, while
      apoptosis comes with iodine-induced involution.

PMID- 11834456
TI  - Effects of oestrogen deprivation on interleukin-6 production by peripheral blood
      mononuclear cells of postmenopausal women.
AB  - Various hormones can influence the expression of interleukin-6 (IL-6) and
      oestrogens are the most extensively studied. There is, however, controversy about
      the nature of the IL-6 secreted by human cells and its regulation by 17beta
      oestradiol. The aim of this work was to clarify whether oestrogen deprivation
      after menopause may contribute to an enhanced IL-6 production by peripheral blood
      mononuclear cells (PBMC) in postmenopausal women. Twenty-two healthy
      postmenopausal women, age range 45-63 years, with clinical symptoms of oestrogen
      deficiency were enrolled in the study. The control group consisted of 16 healthy
      young women, age range 22-31 years, with regular menses and who were not taking
      oral contraceptives. Levels of IL-6 in the sera and PBMC culture supernatants
      were measured by the biological B9 cell-proliferation assay and expression of the
      IL-6 gene in non-stimulated PBMC was detected by RT-PCR. The effect of 17beta
      oestradiol on spontaneous IL-6 production by the PBMC of postmenopausal women was
      also studied in vitro and in vivo. Seventeen out of the twenty-two postmenopausal
      women were given hormonal replacement therapy of 50 microg 17beta-oestradiol/day
      transdermally and the spontaneous production of IL-6 by the PBMC was analysed
      after 6 and 12 months of treatment. The postmenopausal women had significantly
      higher serum levels of IL-6 than the young controls. The spontaneous production
      of IL-6 by non-stimulated PBMC into the culture supernatants was also
      significantly higher in the postmenopausal women compared with the young. We also
      found that IL-6 gene expression was present in the non-stimulated PBMC isolated
      directly from the venous blood of the majority of the postmenopausal women. Women
      with IL-6 gene expression in the non-stimulated PBMC had significantly lower
      serum levels of 17beta-oestradiol compared with those where the IL-6 gene was not
      expressed in the PBMC. Our in vitro experiments showed that 17beta-oestradiol at
      concentrations of 10(-9) M and 10(-10) M decreased spontaneous IL-6 production by
      the PBMC of postmenopausal women. In vivo treatment with 17beta-oestradiol
      transdermally also significantly decreased spontaneous IL-6 production by the
      PBMC of postmenopausal women after 12 months of the therapy. Our results indicate
      that oestrogen deprivation after menopause may enhance IL-6 production by the
      PBMC of postmenopausal women. We suspect that the late complications of oestrogen
      deficiency, such as osteoporosis, coronary heart disease and Alzheimer's disease,
      may be mediated by an exaggerated production of IL-6 - a cytokine which seems to
      play a pivotal role in the pathogenesis of these age-related diseases.

PMID- 11834457
TI  - Genetic variability in melatonin secretion originates in the number of
      pinealocytes in sheep.
AB  - Genetic variability in plasma melatonin concentrations in ewes results from
      variations in pineal weight. This study investigated whether it is due to a
      difference in the number of pinealocytes, or in their size. Two groups of lambs
      were assigned before birth to being extremes (18 High and 21 Low) by calculating
      their genetic value on the basis of the melatonin concentrations of their
      parents. Lambs were bled from 1 week of age until 14 weeks of age. Pineal gland,
      brain and pituitary weights, length and width of the brain, and length of the
      hypothalamus were recorded. A significant effect (ANOVA) of genetic group
      (P<0.05) and age (P<0.05) was detected on mean nocturnal plasma melatonin
      concentrations, as soon as the first week after birth (mean +/- s.e.m.; High:
      51.7 +/- 10.7 vs Low: 31.9 +/- 3.2 pg/ml). There was no difference between the
      two genetic groups in any of the brain parameters measured, but the pineal glands
      of the High group were heavier and contained significantly more pinealocytes
      (High: 27.8 +/- 2.4 vs Low: 21.0 +/- 2.4 x 10(6); P<0.05) than those in the Low
      group. The mean size of pinealocytes did not differ between the two genetic
      groups. Thus, the genetic variability in nocturnal plasma melatonin
      concentrations in sheep is expressed by 1 week of age and higher levels of
      secretion are the consequence of larger pineal glands containing a greater number
      of pinealocytes.

PMID- 11834459
TI  - Proteomic approaches to characterize protein modifications: new tools to study
      the effects of environmental exposures.
AB  - Proteomics is the study of proteomes, which are the collections of proteins
      expressed in cells. Whereas genomes are essentially invariant in different cells
      in an organism, proteomes vary from cell to cell, with time and as a function of
      environmental stimuli and stress. The integration of new mass spectrometry (MS)
      methods, data analysis algorithms, and information from databases of protein and
      gene sequences has enabled the characterization of proteomes. Many environmental
      agents directly or indirectly generate reactive electrophiles that covalently
      modify proteins. Although considerable evidence supports a key role for protein
      adducts in adverse effects of chemicals, limitations in analytical technology
      have slowed progress in this area. New applications of liquid chromatography
      tandem mass spectrometry (LC-MS-MS) now offer the potential to identify protein
      targets of reactive electrophiles and to map adducts at the level of amino acid
      sequence. Use of the data-analysis tools Sequest and SALSA (Scoring Algorithm for
      Spectral Analysis) together with LC-MS-MS analyses of protein digests enables the
      identification of modified forms of proteins in a sample. These approaches can
      map adducts to specific amino acids in protein targets and are being adapted to
      searches for protein adducts in complex proteomes. These tools will facilitate
      the identification of new biomarkers of chemical exposure and studies of
      mechanisms by which protein modifications contribute to the adverse effects of
      environmental exposures.

PMID- 11834460
TI  - The three modern faces of mercury.
AB  - The three modern "faces" of mercury are our perceptions of risk from the exposure
      of billions of people to methyl mercury in fish, mercury vapor from amalgam tooth
      fillings, and ethyl mercury in the form of thimerosal added as an antiseptic to
      widely used vaccines. In this article I review human exposure to and the
      toxicology of each of these three species of mercury. Mechanisms of action are
      discussed where possible. Key gaps in our current knowledge are identified from
      the points of view both of risk assessment and of mechanisms of action.

PMID- 11834462
TI  - U.S. drinking water challenges in the twenty-first century.
AB  - The access of almost all 270 million U.S. residents to reliable, safe drinking
      water distinguishes the United States in the twentieth century from that of the
      nineteenth century. The United States is a relatively water-abundant country with
      moderate population growth; nonetheless, current trends are sufficient to strain
      water resources over time, especially on a regional basis. We have examined the
      areas of public water infrastructure, global climate effects, waterborne disease
      (including emerging and resurging pathogens), land use, groundwater, surface
      water, and the U.S. regulatory history and its horizon. These issues are
      integrally interrelated and cross all levels of public and private jurisdictions.
      We conclude that U.S. public drinking water supplies will face challenges in
      these areas in the next century and that solutions to at least some of them will
      require institutional changes.

PMID- 11834463
TI  - Assessing exposure in epidemiologic studies to disinfection by-products in
      drinking water: report from an international workshop.
AB  - The inability to accurately assess exposure has been one of the major
      shortcomings of epidemiologic studies of disinfection by-products (DBPs) in
      drinking water. A number of contributing factors include a) limited information
      on the identity, occurrence, toxicity, and pharmacokinetics of the many DBPs that
      can be formed from chlorine, chloramine, ozone, and chlorine dioxide
      disinfection; b) the complex chemical interrelationships between DBPs and other
      parameters within a municipal water distribution system; and c) difficulties
      obtaining accurate and reliable information on personal activity and water
      consumption patterns. In May 2000, an international workshop was held to bring
      together various disciplines to develop better approaches for measuring DBP
      exposure for epidemiologic studies. The workshop reached consensus about the
      clear need to involve relevant disciplines (e.g., chemists, engineers,
      toxicologists, biostatisticians and epidemiologists) as partners in developing
      epidemiologic studies of DBPs in drinking water. The workshop concluded that
      greater collaboration of epidemiologists with water utilities and regulators
      should be encouraged in order to make regulatory monitoring data more useful for
      epidemiologic studies. Similarly, exposure classification categories in
      epidemiologic studies should be chosen to make results useful for regulatory or
      policy decision making.

PMID- 11834464
TI  - Drinking water contaminants and adverse pregnancy outcomes: a review.
AB  - Concern for exposures to drinking water contaminants and their effects on adverse
      birth outcomes has prompted several studies evaluating chlorination disinfection
      by-products and chlorinated solvents. Some of these contaminants are found to be
      teratogenic in animal studies. This review evaluates 14 studies on chlorination
      disinfection by-products such as trihalomethanes (THMs) and five studies on
      chlorinated solvents such as trichloroethylene (TCE). The adverse birth outcomes
      discussed in this review include small for gestational age (SGA), low birth
      weight, preterm birth, birth defects, spontaneous abortions, and fetal deaths.
      Because of heterogeneities across the studies in the characterization of birth
      outcomes, the assessment and categorization of exposures, and the levels and
      mixtures of contaminants, a qualitative review was conducted. Generally, the
      chief bias in these studies was exposure misclassification that most likely
      underestimated the risk, as well as distorted exposure-response relationships.
      The general lack of confounding bias by risk factors resulted from these factors
      not being associated with drinking water exposures. The studies of THMs and
      adverse birth outcomes provide moderate evidence for associations with SGA,
      neural tube defects (NTDs), and spontaneous abortions. Because fewer studies have
      been conducted for the chlorinated solvents than for THMs, the evidence for
      associations is less clear. Nevertheless, the findings of excess NTDs, oral
      clefts, cardiac defects, and choanal atresia in studies that evaluated TCE
      contaminated drinking water deserve follow-up.

PMID- 11834465
TI  - Use of mechanism-based structure-activity relationships analysis in carcinogenic
      potential ranking for drinking water disinfection by-products.
AB  - Disinfection by-products (DBPs) are formed when disinfectants such as chlorine,
      chloramine, and ozone react with organic and inorganic matter in water. The
      observations that some DBPs such as trihalomethanes (THMs), di-/trichloroacetic
      acids, and 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) are
      carcinogenic in animal studies have raised public concern over the possible
      adverse health effects of DBPs. To date, several hundred DBPs have been
      identified. To prioritize research efforts, an in-depth, mechanism-based
      structure-activity relationship analysis, supplemented by extensive literature
      search for genotoxicity and other data, was conducted for ranking the
      carcinogenic potential of DBPs that met the following criteria: a) detected in
      actual drinking water samples, b) have insufficient cancer bioassay data for risk
      assessment, and c) have structural features/alerts or short-term predictive
      assays indicative of carcinogenic potential. A semiquantitative concern rating
      scale of low, marginal, low-moderate, moderate, high-moderate, and high was used
      along with delineation of scientific rationale. Of the 209 DBPs analyzed, 20 were
      of priority concern with a moderate or high-moderate rating. Of these, four were
      structural analogs of MX and five were haloalkanes that presumably will be
      controlled by existing and future THM regulations. The other eleven DBPs, which
      included halonitriles (6), haloketones (2), haloaldehyde (1), halonitroalkane
      (1), and dialdehyde (1), are suitable priority candidates for future
      carcinogenicity testing and/or mechanistic studies.

PMID- 11834461
TI  - Understanding the human health effects of chemical mixtures.
AB  - Most research on the effects of chemicals on biologic systems is conducted on one
      chemical at a time. However, in the real world people are exposed to mixtures,
      not single chemicals. Although various substances may have totally independent
      actions, in many cases two substances may act at the same site in ways that can
      be either additive or nonadditive. Many even more complex interactions may occur
      if two chemicals act at different but related targets. In the extreme case there
      may be synergistic effects, in which case the effects of two substances together
      are greater than the sum of either effect alone. In reality, most persons are
      exposed to many chemicals, not just one or two, and therefore the effects of a
      chemical mixture are extremely complex and may differ for each mixture depending
      on the chemical composition. This complexity is a major reason why mixtures have
      not been well studied. In this review we attempt to illustrate some of the
      principles and approaches that can be used to study effects of mixtures. By the
      nature of the state of the science, this discussion is more a presentation of
      what we do not know than of what we do know about mixtures. We approach the study
      of mixtures at three levels, using specific examples. First, we discuss several
      human diseases in relation to a variety of environmental agents believed to
      influence the development and progression of the disease. We present results of
      selected cellular and animal studies in which simple mixtures have been
      investigated. Finally, we discuss some of the effects of mixtures at a molecular
      level.

PMID- 11834466
TI  - Biologic effects of oil fly ash.
AB  - Epidemiologic studies have demonstrated increased human morbidity and mortality
      with elevations in the concentration of ambient air particulate matter (PM).
      Fugitive fly ash from the combustion of oil and residual fuel oil significantly
      contributes to the ambient air particle burden. Residual oil fly ash (ROFA) is
      remarkable in the capacity to provoke injury in experimental systems. The unique
      composition of this emission source particle makes it particularly useful as a
      surrogate for ambient air PM in studies of biologic effects testing the
      hypothesis that metals mediate the biologic effects of air pollution particles. A
      majority of the in vitro and animal model investigations support the postulate
      that transition metals present in ROFA (especially vanadium) participate in
      Fenton-like chemical reactions to produce reactive oxygen species. This is
      associated with tyrosine phosphorylation, nuclear factor kappa B and other
      transcription factor activation, induction of inflammatory mediator expression,
      and inflammatory lung injury. It is also evident that vanadium accounts for a
      significant portion of the biologic activity of ROFA. The extrapolation of this
      body of investigation on ROFA to the field of ambient air PM is difficult, as
      particles in numerous environments have such small amounts of vanadium.

PMID- 11834469
TI  - Environmental medicine in Germany--a review.
AB  - In this review I describe the development of environmental medicine as a
      specialized field of clinical medicine in Germany. New scientific societies were
      founded, based on traditions of public hygiene and occupational medicine, as a
      reaction to environmental issues concerning human health. Environmental medicine
      issues were also addressed by independent "critical" physicians. The first
      institutions to accept patients were centers for environmental medicine
      affiliated with research institutions and/or with the public health service.
      Medical professional organizations, particularly the German General Medical
      Council, described the need for and formulated conditions for additional
      qualification for doctors in environmental medicine, including a 200-hr course.
      This course and a qualifying exam were passed by about 3,000 doctors, mainly from
      the public health service and from occupational medicine. Unfortunately, few
      general physicians in primary outpatient care were similarly trained. To date, no
      representative study has been conducted on environmental patients, but I include
      in this review a typical list of patients' complaints. I also summarize research
      activities typical for environmental medicine in Germany. Present problems
      concern accounting systems and, for example, diagnosis and treatment of patients
      with multiple chemical sensitivities (MCS). A coordinated research program on MCS
      has been started.

PMID- 11834468
TI  - Diesel exhaust and asthma: hypotheses and molecular mechanisms of action.
AB  - Several components of air pollution have been linked to asthma. In addition to
      the well-studied critera air pollutants, such as nitrogen dioxide, sulfur
      dioxide, and ozone, diesel exhaust and diesel exhaust particles (DEPs) also
      appear to play a role in respiratory and allergic diseases. Diesel exhaust is
      composed of vapors, gases, and fine particles emitted by diesel-fueled
      compression-ignition engines. DEPs can act as nonspecific airway irritants at
      relatively high levels. At lower levels, DEPs promote release of specific
      cytokines, chemokines, immunoglobulins, and oxidants in the upper and lower
      airway. Release of these mediators of the allergic and inflammatory response
      initiates a cascade that can culminate in airway inflammation, mucus secretion,
      serum leakage into the airways, and bronchial smooth muscle contraction. DEPs
      also may promote expression of the T(subscript)H(/subscript)2 immunologic
      response phenotype that has been associated with asthma and allergic disease.
      DEPs appear to have greater immunologic effects in the presence of environmental
      allergens than they do alone. This immunologic evidence may help explain the
      epidemiologic studies indicating that children living along major trucking
      thoroughfares are at increased risk for asthmatic and allergic symptoms and are
      more likely to have objective evidence of respiratory dysfunction.

PMID- 11834471
TI  - Antioxidant therapy for atherosclerotic vascular disease: the promise and the
      pitfalls.

PMID- 11834467
TI  - Use of an index to reflect the aggregate burden of long-term exposure to criteria
      air pollutants in the United States.
AB  - Air pollution control in the United States for five common pollutants-
      particulate matter, ground-level ozone, sulfur dioxide, nitrogen dioxide, and
      carbon monoxide--is based partly on the attainment of ambient air quality
      standards that represent a level of air pollution regarded as safe. Regulatory
      and health agencies often focus on whether standards for short periods are
      attained; the number of days that standards are exceeded is used to track
      progress. Efforts to explain air pollution to the public often incorporate an air
      quality index that represents daily concentrations of pollutants. While effects
      of short-term exposures have been emphasized, research shows that long-term
      exposures to lower concentrations of air pollutants can also result in adverse
      health effects. We developed an aggregate index that represents long-term
      exposure to these pollutants, using 1995 monitoring data for metropolitan areas
      obtained from the U.S. Environmental Protection Agency's Aerometric Information
      Retrieval System. We compared the ranking of metropolitan areas under the
      proposed aggregate index with the ranking of areas by the number of days that
      short-term standards were exceeded. The geographic areas with the highest burden
      of long-term exposures are not, in all cases, the same as those with the most
      days that exceeded a short-term standard. We believe that an aggregate index of
      long-term air pollution offers an informative addition to the principal
      approaches currently used to describe air pollution exposures; further work on an
      aggregate index representing long-term exposure to air pollutants is warranted.

PMID- 11834472
TI  - The promise of translational physiology.

PMID- 11834473
TI  - L-arginine protects human heart cells from low-volume anoxia and reoxygenation.
AB  - Protective effects of L-arginine were evaluated in a human ventricular heart cell
      model of low-volume anoxia and reoxygenation independent of alternate cell types.
      Cell cultures were subjected to 90 min of low-volume anoxia and 30 min of
      reoxygenation. L-Arginine (0-5.0 mM) was administered during the preanoxic period
      or the reoxygenation phase. Nitric oxide (NO) production, NO synthase (NOS)
      activity, cGMP levels, and cellular injury were assessed. To evaluate the effects
      of the L-arginine on cell signaling, the effects of the NOS antagonist N(G)-nitro
      L-arginine methyl ester, NO donor S-nitroso-N-acetyl-penicillamine, guanylate
      cyclase inhibitor methylene blue, cGMP analog 8-bromo-cGMP, and ATP-sensitive K+
      channel antagonist glibenclamide were examined. Our data indicate that low-volume
      anoxia and reoxygenation increased NOS activity and facilitated the conversion of
      L-arginine to NO, which provided protection against cellular injury in a dose
      dependent fashion. In addition, L-arginine cardioprotection was achieved by the
      activation of guanylate cyclase, leading to increased cGMP levels in human heart
      cells. This action involves a glibenclamide-sensitive, NO-cGMP-dependent pathway.

PMID- 11834474
TI  - Augmented adrenergic vasoconstriction in hypertensive diabetic obese Zucker rats.
AB  - This study examined skeletal muscle microvessel reactivity to constrictor stimuli
      in obese (OZR) versus lean Zucker rats (LZR). Gracilis arteries from both rat
      groups were isolated, cannulated with glass micropipettes, and viewed via
      television microscopy. Changes in vessel diameter were measured with a video
      micrometer. Arterial constriction to norepinephrine was elevated in OZR versus
      LZR, although vasoconstrictor reactivity to endothelin and angiotensin II was
      unaltered. Differences in reactivity between vessels of LZR and OZR were not
      explained by the loss of either endothelial nitric oxide synthase or beta
      adrenergic receptor function. Reactivity of in situ cremasteric arterioles of OZR
      to norepinephrine was elevated versus LZR. Treatment with prazosin increased the
      diameter of in vivo gracilis arteries of OZR to levels determined in LZR and also
      normalized blood pressure in OZR. These results suggest that the constrictor
      reactivity of skeletal muscle microvessels in OZR is heightened in response to
      alpha-adrenergic stimuli and that development of diabetes in OZR may be
      associated with impaired skeletal muscle perfusion and hypertension due to
      microvessel hyperreactivity in response to sympathetic stimulation.

PMID- 11834470
TI  - Perspectives on the chemical etiology of breast cancer.
AB  - Multiple factors, known and unknown, contribute to human breast cancer.
      Hereditary, hormonal, and reproductive factors are associated with risk of breast
      cancer. Environmental agents, including chemical carcinogens, are modifiable risk
      factors to which over 70% of breast cancers have been attributed. Polymorphisms
      of drug-metabolizing enzymes may influence risk of breast cancer from
      environmental chemicals, dietary agents, and endogenous steroids. The
      environmental factors discussed in this review include pollutants, occupational
      exposures, tobacco smoke, alcohol, and diet. Aromatic amines are discussed as
      potential mammary carcinogens, with a focus on heterocyclic amine food pyrolysis
      products. These compounds are excreted into the urine after consumption of meals
      containing cooked meats and have recently been detected in the breast milk of
      lactating women.

PMID- 11834475
TI  - Alteration of mitochondrial function in a model of chronic ischemia in vivo in
      rat heart.
AB  - The aim of this study was to investigate mitochondrial alterations in an animal
      model of chronic myocardial ischemia in rats obtained by surgical constriction of
      the left coronary artery. Resting coronary blood flow was measured using the
      fluorescent microsphere technique. Contractile function, defined by rate-pressure
      product, and myocardial oxygen consumption were measured in a Langendorff
      preparation. The mitochondrial function was evaluated on permeabilized skinned
      fibers. Three weeks after surgery, ischemic hearts showed a significant decrease
      in coronary blood flow compared with sham. Hemodynamic measurements showed a
      significant systolic and diastolic dysfunction. Alterations in mitochondrial
      function in ischemic hearts were mainly characterized by a significant decrease
      in the maximal velocity and apparent half-saturation constant for ADP, loss of
      the stimulatory effect of creatine, and a stimulatory effect of exogenous
      cytochrome c. These functional alterations were supported by structural
      alterations characterized by mitochondrial clustering and swelling associated
      with membrane rupture. We conclude that the alterations in systolic function
      after chronic ischemia are supported by severe modifications of mitochondrial
      structure and function.

PMID- 11834476
TI  - Regional cerebral blood flow in cats with cross-linked hemoglobin transfusion
      during focal cerebral ischemia.
AB  - The beneficial effect of hemodilution on cerebral blood flow (CBF) during focal
      cerebral ischemia is mitigated by reduced arterial oxygen content (CaO2). In
      anesthetized cats subjected to permanent middle cerebral artery occlusion, the
      time course of regional CBF was evaluated after isovolemic exchange transfusion
      with either albumin or a tetrameric hemoglobin-based oxygen carrier. The
      transfusion started 30 min after arterial occlusion. We tested the hypothesis
      that bulk oxygen transport (CBF x CaO2) to ischemic tissue is increased by
      hemoglobin transfusion at a hematocrit of 18% compared with albumin-transfused
      cats at a hematocrit of 18% or control cats at a hematocrit of 30% and equivalent
      arterial pressure. In the nonischemic hemisphere, CBF increased selectively after
      albumin transfusion, and oxygen transport was similar among groups. In the
      ischemic cortex, albumin transfusion increased CBF, but oxygen transport was not
      increased above that of the control group. Hemoglobin transfusion increased both
      CBF and oxygen transport in the ischemic cortex above values in the control
      group, but the increase was delayed until 4 h of ischemia. Consequently, acute
      injury volume measured at 6 h of ischemia was not significantly attenuated. In
      contrast to the cortex, CBF in the ischemic caudate nucleus was not substantially
      increased by either albumin or hemoglobin transfusion. Therefore, in a large
      animal model of permanent focal ischemia in which transfusion starts 30 min after
      ischemia, tetrameric cross-linked hemoglobin transfusion can augment oxygen
      transport to the ischemic cortex, but the increase can be delayed and not
      necessarily provide protection. Moreover, an end-artery region such as the
      caudate nucleus is less likely to benefit from hemodilution.

PMID- 11834477
TI  - A possible role for atrial fibroblasts in postinfarction bradycardia.
AB  - Atrial fibroblasts are considered to modulate the contractile activity of the
      heart in response to mechanical stretch. In this study we examined whether atrial
      fibroblasts are possibly involved in bradyarrhythmia, which is a severe
      complication after myocardial infarction. For this purpose, transmembrane
      electrical potentials were recorded in cardiac fibroblasts near the sinoatrial
      node from sham-operated rats and from rats with myocardial infarction. Twenty
      days after infarction due to coronary artery ligation, the right atrial tissue
      weights and the sensitivity of the fibroblast membrane potential to mechanical
      stretch correlated positively with the infarct size. Cardiac growth was enhanced,
      but the stretch sensitivity and the resting membrane potential of the atrial
      fibroblasts declined between 8 and 30 days after infarction. The frequency of
      spontaneous atrial contractions was significantly reduced 8 days after myocardial
      infarction and recovered in parallel with the membrane potential of the
      fibroblasts. These findings suggest that changes in the susceptibility of atrial
      fibroblasts to mechanical stretch may contribute to bradyarrhythmia during
      postinfarct remodeling of the heart.

PMID- 11834478
TI  - Absorption of amniotic fluid by amniochorion in sheep.
AB  - Swallowing of amniotic fluid and lung fluid inflow were eliminated in 10
      chronically instrumented fetuses. The urachus was ligated, and fetal was urine
      drained to the outside. At the beginning and the end of 21 experiments of 66 +/-
      5 (SE) h duration, all amniotic fluid was temporarily drained to the outside for
      volume measurement and sampling. Amniotic fluid osmolalities and oncotic
      pressures were experimentally controlled. Amniochorionic absorption of amniotic
      fluid depended strongly on the osmolality difference between amniotic fluid and
      fetal plasma (P < 0.001), but at zero osmolality difference there still was a
      mean absorption rate of 23.8 +/- 4.7 (SE) ml/h (P < 0.001). Absorption was
      unaffected by the protein concentration difference between amniotic fluid and
      fetal plasma, but infused bovine albumin in the amniotic fluid was absorbed at a
      rate of 1.8 8 +/- 0.4 g/h (P < 0.001), corresponding to a volume flow of fluid of
      33.8 8 +/- 6.1 ml/h (P < 0.001). Fluid absorption in the amniochorion is driven
      in part by crystalloid osmotic pressure, but about 25 ml/h is absorbed by a path
      that is permeable to protein. That path has the physiological characteristics of
      lymphatic drainage, although no anatomic basis is known to exist for a lymphatic
      system in the amniochorion.

PMID- 11834479
TI  - Transmural recording of monophasic action potentials.
AB  - To investigate the possibility of transmural recording of repolarization through
      the ventricular wall, KCl monophasic action potential (MAP) electrodes positioned
      along plunge needles were developed and tested. The MAP electrode consists of a
      silver wire surrounded by agarose gel containing KCl, which slowly eluted into
      the adjacent tissue to depolarize it. In six dogs, a plunge needle containing
      three KCl MAP electrodes was inserted into the left ventricle to simultaneously
      record from the subepicardium, midwall, and subendocardium. In six pigs, eight
      plunge needles containing three KCl MAP electrodes and two plunge needles
      containing similar electrodes except for the absence of KCl were inserted into
      the ventricles. In three guinea pig papillary muscles, a KCl electrode was used
      to record MAPs along with two microelectrodes for recording transmembrane
      potentials. Transmural MAP recordings could be made for >1 h in dogs and >2 h in
      pigs with a significant decrease in MAP amplitude over time but without a
      significant change in MAP duration. With the electrodes without KCl in pigs, the
      injury potentials subsided in <30 min. When the pacing rate was changed to alter
      the action potential duration and refractory period in dogs, the MAP duration
      correlated with the local effective refractory period (r = 0.94). The time course
      of the MAP duration recorded with a KCl MAP electrode in guinea pig papillary
      muscles corresponded well with that of the transmembrane potential recorded with
      an adjacent microelectrode. It is possible to record transmural repolarization of
      the ventricles with KCl MAP electrodes on plunge needles. The MAP is caused by
      the KCl rather than being a nonspecific injury potential.

PMID- 11834480
TI  - Nitric oxide-endothelin-1 interactions after acute ductal constriction in fetal
      lambs.
AB  - Acute partial compression of the fetal ductus arteriosus (DA) results in an
      initial increase in pulmonary blood flow (PBF) that is followed by acute
      vasoconstriction. The objective of the present study was to determine the role of
      nitric oxide (NO)-endothelin-1 (ET-1) interactions in the acute changes in
      pulmonary vascular tone after in utero partial constriction of the DA. Twelve
      late-gestation fetal lambs (132-140 days) were instrumented to measure vascular
      pressures and left PBF. After a 24-h recovery period, acute constriction of the
      DA was performed by partially inflating a vascular occluder, and the hemodynamic
      variables were observed for 4 h. In control lambs (n = 7), acute ductal
      constriction initially increased PBF by 627% (P < 0.05). However, this was
      followed by active vasoconstriction, such that PBF was restored to
      preconstriction values by 4 h. This was associated with a 43% decrease in total
      NO synthase (NOS) activity (P < 0.05) and a 106% increase in plasma ET-1 levels
      (P < 0.05). Western blot analysis demonstrated no changes in lung tissue
      endothelial NOS, preproET-1, endothelin-converting enzyme-1, or ET(B) receptor
      protein levels. The infusion of PD-156707 (an ET(A) receptor antagonist, n = 5)
      completely blocked the vasoconstriction and preserved NOS activity. These data
      suggest that the fetal pulmonary vasoconstriction after acute constriction of the
      DA is mediated by NO-ET-1 interactions. These include an increase in ET(A)
      receptor-mediated vasoconstriction and an ET(A) receptor-mediated decrease in NOS
      activity. The mechanisms of these NO-ET-1 interactions, and their role in
      mediating acute changes in PBF, warrant further studies.

PMID- 11834482
TI  - Effects of sustained beta-adrenergic stimulation on ionic currents of cultured
      adult guinea pig cardiomyocytes.
AB  - Short-term stimulation of beta-receptors is known to affect cardiac ion channels;
      however, the impact of longer-term stimulation on intrinsic channel function is
      poorly understood. To evaluate this, cultured guinea pig ventricular myocytes
      were exposed to isoproterenol (10 nM), vehicle, or isoproterenol plus propranolol
      (1 microM) for 48 h. Sustained exposure to isoproterenol decreased the density of
      the inward rectifier (I(K1)), slow delayed rectifier (I(Ks)), and L-type Ca2+
      (I(Ca L)) currents, effects that were fully prevented by propranolol. Changes in
      K+ currents were prevented by the beta1-selective antagonist CGP-20712A,
      unaffected by the beta2-antagonist ICI-118,551, and mimicked by the membrane
      permeable cAMP analog 8-bromo-cAMP. Isoproterenol did not alter the current
      voltage relationship of the K+ currents but increased the density of T-type Ca2+
      current (I(Ca T)) and thereby increased the proportion of the total Ca2+ current
      at more negative potentials. We conclude that sustained exposure to isoproterenol
      reduces I(K1), I(Ks), and I(Ca L) density and increases the density of I(Ca T).
      The direct ionic current remodeling effects of sustained beta-adrenoceptor
      stimulation resemble changes reported with heart failure and may be important in
      arrhythmogenic ionic remodeling.

PMID- 11834481
TI  - Endotoxin stress-response in cardiomyocytes: NF-kappaB activation and tumor
      necrosis factor-alpha expression.
AB  - Although tumor necrosis factor (TNF)-alpha is implicated in numerous cardiac
      pathologies, the intracellular events leading to its production by heart cells
      are largely unknown. The goal of the present study was to identify the role of
      the transcription factor nuclear factor (NF)-kappaB in this process. Among the
      many inducers of TNF-alpha expression in myeloid cells, only lipopolysaccharide
      (LPS) led to its induction in cultured neonatal myocytes. LPS also activated the
      NF-kappaB pathway, as evidenced by the degradation of the inhibitory protein
      IkappaB and the appearance of NF-kappaB-binding complexes in nuclear extracts.
      Furthermore, inhibitors of NF-kappaB activation, such as lactacystin, MG132, and
      pyrrolidine dithiocarbamate, were found to completely block the production of TNF
      alpha in response to LPS stimulation, indicating a requirement of NF-kappaB for
      TNF-alpha expression. However, interleukin-1beta and phorbol 12-myristate 13
      acetate also activated NF-kappaB but did not evoke TNF-alpha expression,
      revealing that this factor is not sufficient for cytokine production. Detailed
      examination of the NF-kappaB cascade revealed that cardiac cells displayed a
      unique pattern of IkappaB degradation in response to LPS, with IkappaBbeta but
      not IkappaBalpha being degraded upon stimulation. Additionally, two specific p65
      containing DNA-binding complexes were observed in the nuclear extracts of
      neonatal cardiomyocytes: an inducible complex that is necessary for TNF-alpha
      expression and a constitutive species. Taken together, these results reveal that
      NF-kappaB is not only involved in cytokine production but also may be linked to
      other pathways that subserve a constitutive, protective mechanism for the heart
      cell.

PMID- 11834483
TI  - Forebrain renin-angiotensin system has a tonic excitatory influence on renal
      sympathetic nerve activity.
AB  - All elements of the renin-angiotensin system (RAS) are present in the forebrain,
      particularly in circumventricular organs surrounding the third cerebral
      ventricle. We tested the hypothesis that forebrain angiotensin-converting enzyme
      (ACE) has a tonic excitatory influence on sympathetic drive. Neurally intact and
      sinoaortic-denervated pentobarbital-anesthetized rats were treated with forebrain
      directed intracarotid artery (ICA) versus intravenous injections of angiotensin I
      (ANG I) and of the ACE inhibitor captopril. In intact rats, ICA ANG I elicited a
      rise in arterial pressure and a concomitant reduction in renal sympathetic nerve
      activity (RSNA; ICA captopril elicited the opposite responses). In barodenervated
      rats, ICA ANG I increased and ICA captopril decreased arterial pressure and RSNA
      in parallel; intravenous ANG I had no effect on RSNA. The findings suggest that
      the intrinsic forebrain RAS has a tonic excitatory influence on sympathetic drive
      that is overshadowed in normal rats by baroreflex mechanisms, but may assume a
      more prominent role in pathophysiological states (e.g., heart failure) in which
      baroreflex mechanisms are impaired and RAS activity is augmented.

PMID- 11834484
TI  - Increased expression of cardiotrophin-1 during ventricular remodeling in
      hypertensive rats.
AB  - Cardiotrophin-1 (CT-1) stimulates longitudinal myocardial cell hypertrophy. We
      examined the expression of CT-1, leukemia inhibitory factor (LIF), and gp130 by
      competitive RT-PCR and Western blotting in Dahl salt-sensitive (DS) rats with a
      high-salt diet, which showed a distinct transition from left ventricular
      hypertrophy (LVH) to congestive heart failure (CHF). The expression levels of CT
      1 mRNA and protein were significantly increased at the CHF stage compared with
      the LVH stage and age-matched Dahl salt-resistant (DR) rats (n = 6 for each
      group). mRNA expression of LIF was not changed in the left ventricle at any stage
      by RT-PCR. gp130 mRNA and protein levels of DS rats at 11 and 17 wk were
      significantly increased compared with age-matched DR rats. The isolated myocyte
      length of DS rats at 17 wk was the longest among the four groups of rats. The LV
      end-diastolic dimension (LVDd) of DS rats, determined by echocardiography, was
      significantly increased at the CHF stage. There was a significant correlation
      between the CT-1 protein level and LVDd. CT-1 may play a role in ventricular
      remodeling during transition from LVH to CHF in the rat hypertensive model.

PMID- 11834485
TI  - Pial arteriole dilation during somatosensory stimulation is not mediated by an
      increase in CSF metabolites.
AB  - Pial arterioles supplying the hindlimb somatosensory cortex dilate in response to
      contralateral sciatic nerve stimulation. The mechanism of this pial vasodilation
      is not well understood. One possibility is that vasoactive metabolites released
      during brain activation may diffuse to subarachnoid cerebrospinal fluid (CSF) to
      dilate pial vessels. To test this hypothesis, we implanted closed cranial windows
      in rats and measured pial arteriolar dilation to sciatic nerve stimulation during
      constant rate superfusion of the pial surface with artificial CSF. We reason that
      flushing the pial surface with CSF should quickly dissipate vasoactive substances
      and prevent these substances from dilating pial arterioles. CSF flow (1 and 1.5
      ml/min) significantly reduced pial arteriole dilation induced by 5% CO2
      inhalation, but the same flow rates did not affect dilator responses to sciatic
      nerve stimulation. We conclude that brain-to-CSF diffusion of vasoactive
      metabolites does not play a significant role in the dilation of pial arterioles
      during somatosensory activity.

PMID- 11834486
TI  - Potassium (BK(Ca)) currents are reduced in microvascular smooth muscle cells from
      insulin-resistant rats.
AB  - Insulin resistance (IR) syndrome is associated with impaired vascular relaxation;
      however, the underlying pathophysiology is unknown. Potassium channel activation
      causes vascular smooth muscle hyperpolarization and relaxation. The present study
      determined whether a reduction in large conductance calcium- and voltage
      activated potassium (BK(Ca)) channel activity contributes to impaired vascular
      relaxation in IR rats. BK(Ca) channels were characterized in mesenteric
      microvessels from IR and control rats. Macroscopic current density was reduced in
      myocytes from IR animals compared with controls. In addition, inhibition of
      BK(Ca) channels with tetraethylammonium (1 mM) or iberiotoxin (100 nM) was
      greater in myocytes from control (70%) compared with IR animals (approximately
      20%). Furthermore, activation of BK(Ca) channels with NS-1619 was three times
      more effective at increasing outward current in cells from control versus IR
      animals. Single channel and Western blot analysis of BK(Ca) channels revealed
      similar conductance, amplitude, voltage sensitivity, Ca2+ sensitivity, and
      expression density between the two groups. These data provide the first direct
      evidence that microvascular potassium currents are reduced in IR and suggest a
      molecular mechanism that could account for impaired vascular relaxation in IR.

PMID- 11834487
TI  - Maternal cardiovascular changes during pregnancy and postpartum in mice.
AB  - Genetically altered mice may provide useful models for exploring cardiovascular
      regulation during pregnancy and postpartum if changes in mice mimic humans. We
      found in awake ICR (CD-1) mice at 17.5 days gestation that hematocrit was reduced
      18%, and the pressor response to intravenous angiotensin II was reduced ~33%.
      Arterial pressure in awake mice was 12% lower in early pregnancy (3.5 days) than
      late pregnancy (17.5 days) and postpartum (3 and 17 days after delivery), whereas
      heart rate was 10-20% higher in the peripartum period (17.5 days gestation and 3
      days postpartum). In late pregnancy, cardiac output under isoflurane anesthesia
      was 64% higher than in nonpregnant mice, due to a 37% increase in stroke volume
      and a 17% increase in heart rate. All changes P < 0.05. We conclude that, as in
      humans, mice exhibit hypotension in early pregnancy, and a blunted pressor
      response to angiotensin II, a decrease in hematocrit, and a marked increase in
      cardiac output in late pregnancy.

PMID- 11834488
TI  - Differential expression of TNF-alpha, IL-6, and IGF-1 by graded mechanical stress
      in normal rat myocardium.
AB  - An isovolumic normal rat heart Langendorff model was used to examine the effects
      of moderate (15 mmHg) and severe (35 mmHg) mechanical stretch on the time course
      (from 0 to 60 min) of myocardial expression of tumor necrosis factor (TNF)-alpha,
      interleukin (IL)-6, and insulin-like growth factor (IGF)-1 and their cognate
      receptors. After 10 min of moderate stretch, TNF-alpha was de novo expressed,
      whereas constitutive IL-6 and IGF-1 levels were slightly upregulated; no further
      changes occurred up to 60 min. In comparison, severe stretch resulted in a higher
      and progressive increase in TNF-alpha, IL-6, and IGF-1 expression up to 20 min.
      After 20 min, whereas TNF-alpha expression further increased, IL-6 and IGF-1
      levels progressively reduced to values lower than those observed under moderate
      stretch and in unstretched (5 mmHg) control myocardium (IL-6). Mechanical stretch
      did not significantly alter the expression of the cognate receptors. Indeed, the
      TNF-alpha receptor (p55) tended to be progressively upregulated under severe
      stretch over time. The current data provide the first demonstration that TNF
      alpha, IL-6, and IGF-1 ligand-receptor systems are differentially expressed
      within the normal rat myocardium in response to graded mechanical stretch. Such
      findings may have potential implications with regard to compensatory hypertrophy
      and failure.

PMID- 11834489
TI  - Increased expression of HSP27 protects canine myocytes from simulated ischemia
      reperfusion injury.
AB  - Previous studies have shown that adult rat myocytes can be protected from
      simulated ischemia-reperfusion (I/R) injury by small heat shock proteins (sHSPs).
      However, to date the cardioprotective effect of sHSPs has not been confirmed in
      adult myocytes from a large animal species. Left ventricular myocytes from adult
      dogs were cultured and infected with a replication-deficient adenovirus designed
      to increase expression of the human form of HSP27. The response to simulated I/R
      injury was compared using morphologic criteria. Virus-infected myocytes expressed
      two- to threefold more HSP27 and sustained less injury in response to simulated
      I/R than control cells (P < 0.001; paired t-test). Canine myocytes can be
      isolated, cultured, and induced to increase the expression of a foreign protein
      without significant effects on differentiation and/or viability. Increased
      expression of HSP27 provides significant protection from simulated I/R injury in
      adult canine myocytes. Determining the mechanism by which sHSPs protect from
      lethal cell injury will provide important new insights into the mechanism of
      irreversible cell injury in adult myocardium.

PMID- 11834490
TI  - Wine polyphenols improve cardiovascular remodeling and vascular function in NO
      deficient hypertension.
AB  - The effects of the red wine polyphenolic compounds (Provinol) on hypertension,
      left ventricular hypertrophy, myocardial fibrosis, and vascular remodeling were
      investigated after chronic inhibition of nitric oxide (NO) synthase by
      administration of N(G)-nitro-L-arginine methyl ester (L-NAME) to rats. Rats were
      divided into four groups: a control group, a group treated for 4 wk with L-NAME
      (40 mg x kg(-1) x day(-1)), and two groups treated with L-NAME followed by 3 wk
      of either spontaneous recovery or recovery with Provinol treatment (40 mg x kg(
      1) x day(-1)). Administration of Provinol produced a greater readiness of the
      decrease in blood pressure than that in the spontaneous recovery group. Provinol
      significantly depressed myocardial fibrosis and expedited the decrease in aortic
      cross-sectional area, the increase in endothelium-dependent relaxation, and the
      decrease in contraction of the aorta. These effects of Provinol were associated
      with a greater increase of NO synthase activity in the left ventricle and the
      aorta. The present study provides evidence that Provinol accelerates the
      regression of blood pressure and improves structural and functional
      cardiovascular changes produced by chronic inhibition of NO synthesis.

PMID- 11834491
TI  - Cardiac overexpression of A1-adenosine receptor protects intact mice against
      myocardial infarction.
AB  - Previous studies have shown that high-level (300-fold normal) cardiac
      overexpression of A1-adenosine receptors (A1-ARs) in transgenic (TG) mice
      protects isolated hearts against ischemia-reperfusion injury. However, this high
      level of overexpression is associated with bradycardia and increased incidence of
      arrhythmia during ischemia in intact mice, which interfered with studies to
      determine whether this line of TG mice might also be protected against myocardial
      infarction (MI) in vivo. For these studies, we therefore selected a line of TG
      mice that overexpresses the A1-AR at more moderate levels (30-fold normal), which
      affords cardioprotection in the isolated heart while minimizing bradycardia and
      arrhythmia during ischemia in intact mice. Wild-type (WT; n = 10) and moderate
      level A1-AR TG (n = 10) mice underwent 45 min of left anterior descending
      coronary artery occlusion, followed by 24-h reperfusion. Infarct size and region
      at risk were determined by triphenyltetrazolium chloride and phthalo blue
      staining, respectively. Infarct size (% region at risk) in WT mice was 52 +/- 3%,
      whereas overexpression of A1-ARs in the TG mice markedly reduced infarct size to
      31 +/- 3% (P < 0.05). Furthermore, contractile function (left ventricular
      ejection fraction) as determined by cardiac magnetic resonance imaging 24 h after
      MI was better preserved in TG vs. WT mice. Cardiac overexpression of A1-ARs
      reduces infarct size by 40% and preserves cardiac function in intact mice after
      MI.

PMID- 11834492
TI  - Cocaine enhances myocarditis induced by encephalomyocarditis virus in murine
      model.
AB  - This study was designed to investigate whether cocaine can exacerbate viral
      myocarditis and increase its incidence. Recent clinical evidence suggests that
      cocaine abuse increases the incidence of myocarditis. However, it has not been
      directly demonstrated that cocaine exposure enhances murine myocarditis. BALB/c
      mice were divided into eight groups: saline control, encephalomyocarditis virus
      (EMCV), 10 mg/kg cocaine (Coc-10), 30 mg/kg cocaine (Coc-30), 50 mg/kg cocaine
      (Coc-50), EMCV+Coc-10, EMCV+Coc-30, EMCV+Coc-50. After inoculation with EMCV, the
      mice were treated daily with either cocaine or saline for 90 days. Mice were
      euthanized at different days after EMCV inoculation. Mortality was recorded and
      myocarditis severity was evaluated. The mortality of the myocarditis mice treated
      with cocaine increased significantly, from 22% (EMCV) to 25.7% (Coc-10+EMCV),
      41.4% (Coc-30+EMCV), and 51.4% (Coc-50+EMCV) (P < 0.05), respectively. The
      incidence and severity of inflammatory cell infiltration and myocardial lesions
      was higher in infected mice exposed to cocaine. Cocaine administered only before
      infection did not exacerbate myocarditis. Norepinephrine (NE) assay showed that
      cocaine exposure significantly increased myocardial NE concentration but this
      increase was partially inhibited in infected animals. Adrenalectomy abolished the
      effect of cocaine on mortality. Furthermore, propranolol, a beta-blocker,
      significantly decreased the enhancing effects of cocaine on myocarditis mice. In
      conclusion, cocaine increases the severity and mortality of viral myocarditis in
      mice. Increased catecholamines may be a major factor responsible for this effect.

PMID- 11834493
TI  - Increased baroreceptor response in mice deficient in monoamine oxidase A and B.
AB  - The recent development of mice doubly deficient for monoamine oxidase A and B
      (MAO-A/B, respectively) has raised questions about the impact of these mutations
      on cardiovascular function, in so far as these animals demonstrate increased
      tissue levels of the vasoactive amines serotonin, norepinephrine, dopamine, and
      phenylethylamine. We recorded femoral arterial pressures and electrocardiograms
      in adult MAO-A/B-deficient mice during halothane-nitrous oxide anesthesia as well
      as 30 min postoperatively. During both anesthesia and recovery, systolic,
      diastolic, and mean arterial pressures were 10-15 mmHg lower in MAO-A/B-deficient
      mice compared with normal controls (P < 0.01). Mutants also showed a greater
      baroreceptor-mediated reduction in heart rate in response to hypertension after
      intravenous pulses of phenylephrine or angiotensin II. Tachycardia elicited in
      response to hypotension after nitroprusside was greater in mutants than in
      controls. Heart rate responsiveness to changes in arterial pressure was abolished
      after administration of glycopyrrolate, with no differences in this phenomenon
      noted between genotypes. These data suggest that prevention of hypertension may
      occur in chronic states of catecholaminergic/indoleaminergic excess by increased
      gain of the baroreflex.

PMID- 11834494
TI  - Direct effect of Pa(CO2) on respiratory sinus arrhythmia in conscious humans.
AB  - Respiratory sinus arrhythmia (RSA) may improve the efficiency of pulmonary gas
      exchange by matching the pulmonary blood flow to lung volume during each
      respiratory cycle. If so, an increased demand for pulmonary gas exchange may
      enhance RSA magnitude. We therefore tested the hypothesis that CO2 directly
      affects RSA in conscious humans even when changes in tidal volume (V(T)) and
      breathing frequency (F(B)), which indirectly affect RSA, are prevented. In seven
      healthy subjects, we adjusted end-tidal PCO2 (PET(CO2)) to 30, 40, or 50 mmHg in
      random order at constant V(T) and F(B). The mean amplitude of the high-frequency
      component of R-R interval variation was used as a quantitative assessment of RSA
      magnitude. RSA magnitude increased progressively with PET(CO2) (P < 0.001). Mean
      R-R interval did not differ at PET(CO2) of 40 and 50 mmHg but was less at 30 mmHg
      (P < 0.05). Because V(T) and F(B) were constant, these results support our
      hypothesis that increased CO2 directly increases RSA magnitude, probably via a
      direct effect on medullary mechanisms generating RSA.

PMID- 11834495
TI  - Acute exercise enhances vasorelaxation by modulating endothelial calcium
      signaling in rat aortas.
AB  - The role of endothelial calcium signaling in exercise-enhanced ACh-induced
      vasorelaxation was examined using male Wistar rats (8~10 wk old) that were
      divided into control and exercise groups. The exercised animals ran on a
      treadmill with progressive increments of speed until exhaustion. After
      decapitation, aortic rings were dissected and loaded with fura 2-AM. After being
      mounted on a tissue flow chamber, vessels were precontracted with phenylephrine,
      and ACh-induced endothelial calcium elevation and vasorelaxation were determined
      simultaneously under an epifluorescence microscope equipped with ratio imaging
      capability. Our results showed that 1) there was logarithmic correlation between
      endothelial calcium elevation and vasorelaxation; 2) acute exercise enhanced ACh
      induced endothelial calcium elevation and vasorelaxation without altering their
      relationship; 3) pretreatment with N(omega)-nitro-L-arginine markedly reduced ACh
      induced vasorelaxation in both groups but suppressed the calcium response only in
      the exercise group; and 4) the exercise effect on endothelial calcium elevation
      was abolished by Ca2+-free buffer or gadolinium. In conclusion, acute exercise
      increases ACh-induced vasorelaxation by increasing the endothelial calcium influx
      and the calcium-dependent nitric oxide release.

PMID- 11834496
TI  - MMP inhibition modulates TNF-alpha transgenic mouse phenotype early in the
      development of heart failure.
AB  - Myocardial extracellular matrix remodeling regulated by matrix metalloproteinases
      (MMPs) is implicated in the progression of heart failure. We hypothesized that
      MMP inhibition may modulate extracellular matrix remodeling and prevent the
      progression of heart failure. The effects of the MMP inhibitor BB-94 (also known
      as batimastat) on MMP expression, collagen expression, collagen deposition,
      collagen denaturation, and left ventricular structure and function in transgenic
      mice with cardiac-restricted overexpression of tumor necrosis factor-alpha (TNF
      alpha) (TNF1.6) were assessed. The results showed that BB-94 reduced the
      expression of collagens, increased insoluble collagen and the ratio of
      undenatured to total soluble collagen, and prevented myocardial hypertrophy and
      diastolic dysfunction in young TNF1.6 mice. Furthermore, the treatment
      significantly improved cumulative survival of TNF1.6 mice. However, MMP
      inhibition did not have salutary effects on ventricular size and function in old
      mice with established heart failure. The results suggest that MMP activation may
      play a critical role in changes of myocardial function through the remodeling of
      extracellular matrix, and MMP inhibition may serve as a potential therapeutic
      strategy for heart failure, albeit within a narrow window during the development
      of heart failure.

PMID- 11834497
TI  - RhoA/Rho kinase and nitric oxide modulate the agonist-induced pulmonary artery
      diameter response time.
AB  - We studied the amplitude and response time (RT; time to 50% of maximal response)
      of pulmonary vasoreactivity and investigated whether the characteristics of
      pulmonary vasoreactivity could be modulated by endothelium removal, nitric oxide
      (NO) synthase inhibition [N(G)-nitro-L-arginine (L-NNA)], RhoA activation
      [lysophosphatidic acid (LPA)] and Rho kinase inhibition (Y-27632). Slow
      acetylcholine-induced pulmonary vasodilation (262 +/- 5 s) was not due to the RT
      of endothelial NO release (45-55 s) and was always longer than RT in renal
      arteries (15 +/- 4 s). The rate-determining step is located in the smooth muscle
      cells. This was confirmed by the existing differences between the RT of the NO
      solution and KCl-induced renal and pulmonary vasoreactivity in endothelium
      denuded arteries. We found that the pulmonary contractile amplitude increases and
      the RT decreases by L-NNA or LPA. In contrast, Y-27632 reduced the contractile
      amplitude and increased the RT in pulmonary arteries. These phenomena were
      dependent on the contractile stimulus (phenylephrine or KCl). In conclusion, slow
      pulmonary vasoreactivity is a smooth muscle cell characteristic that can be
      enhanced by RhoA and NO or endothelium removal. These effects were counteracted
      by Rho kinase inhibition. We show a role for RhoA/Rho kinase and NO in the
      modulation of pulmonary vascular reactivity.

PMID- 11834498
TI  - Baicalein attenuates oxidant stress in cardiomyocytes.
AB  - Flavonoids within Scutellaria baicalensis may be potent antioxidants on the basis
      of our studies of S. baicalensis extract. To further this work, we studied the
      antioxidative effects of baicalein, a flavonoid component of S. baicalensis, in a
      chick cardiomyocyte model of reactive oxygen species (ROS) generation during
      hypoxia, simulated ischemia-reperfusion, or mitochondrial complex III inhibition
      with antimycin A. Oxidant stress was measured by oxidation of the intracellular
      probes 2',7'-dichlorofluorescin diacetate and dihydroethidium. Viability was
      assessed by propidium iodide uptake. Baicalein attenuated oxidant stress during
      all conditions studied and acted within minutes of treatment. For example,
      baicalein given only at reperfusion dose dependently attenuated the ROS burst at
      5 min after 1 h of simulated ischemia. It also decreased subsequent cell death at
      3 h of reperfusion from 52.3 +/- 2.5% in untreated cells to 29.4 +/- 3.0% (with
      return of contractions; P < 0.001). In vitro studies using electron paramagnetic
      resonance spectroscopy with the spin trap 5-methoxycarbonyl-5-methyl-1-pyrroline
      N-oxide revealed that baicalein scavenges superoxide but does not mimic the
      effects of superoxide dismutase. We conclude that baicalein can scavenge ROS
      generation in cardiomyocytes and that it protects against cell death in an
      ischemia-reperfusion model when given only at reperfusion.

PMID- 11834499
TI  - Mouse heart Na+ channels: primary structure and function of two isoforms and
      alternatively spliced variants.
AB  - We isolated two full-length cDNA clones from the adult murine heart that encode
      two different voltage-gated Na+ channels: mH1 and mH2. Sequence comparisons
      indicated that mH1 is highly homologous to rat SCN5A, whereas mH2 is highly
      homologous to SCN4A, expressed in rat skeletal muscle. Electrophysiological
      properties of mH1 channels strongly resembled the tetrodotoxin (TTX)-resistant
      Na+ current of mouse ventricular cells, whereas mH2 channels activated at more
      positive potentials and were highly sensitive to TTX [50% inhibitory constant
      (IC50) = 11 nM]. We found that mH2 is not expressed in cardiac cells of neonatal
      mice, but appears to be upregulated during the development. Besides these Na+
      channel isoforms, we also detected two alternatively spliced mH1 variants that
      were characterized by deletions within the sequence coding for the intracellular
      loop between domains II and III. One of the shortened channels, mH1-2, developed
      Na+ currents indistinguishable from those of mH1. The other splice variant (mH1
      3) did not form functional channels. Quantitative reverse transcriptase
      polymerase chain reaction indicated that RNA preparations of the adult mouse
      heart contain 54% mH1, 25% mH1-2, 16% mH2, and 5% mH1-3. Conclusively, mH1
      generates the main portion of the mouse cardiac TTX-resistant Na+ current and mH2
      is a candidate for TTX-sensitive currents previously described in adult
      cardiomyocytes. Furthermore, the presence of mH1-2 and mH1-3 transcripts
      indicates that alternative splicing plays a role in the regulation of functional
      Na+ channels in cardiomyocytes.

PMID- 11834500
TI  - Theoretical analysis of rest and exercise hemodynamics in patients with total
      cavopulmonary connection.
AB  - The objective of this study was to determine the impact of a total cavopulmonary
      connection on the main hemodynamic quantities, both at rest and during exercise,
      when compared with normal biventricular circulation. The analysis was performed
      by means of a mathematical model of the cardiovascular system. The model
      incorporates the main parameters of systemic and pulmonary circulation, the
      pulsating heart, and the action of arterial and cardiopulmonary baroreflex
      mechanisms. Furthermore, the effect of changes in intrathoracic pressure on
      venous return is also incorporated. Finally, the response to moderate dynamic
      exercise is simulated, including the effect of a central command, local metabolic
      vasodilation, and the "muscle pump" mechanism. Simulations of resting conditions
      indicate that the action of baroreflex regulatory mechanisms alone can only
      partially compensate for the absence of the right heart. Cardiac output and mean
      systemic arterial pressure at rest show a large decrease compared with the normal
      subject. More acceptable hemodynamic quantity values are obtained by combining
      the action of regulatory mechanisms with a chronic change in parameters affecting
      mean filling pressure. With such changes assumed, simulations of the response to
      moderate exercise show that univentricular circulation exhibits a poor capacity
      to increase cardiac output and to sustain aerobic metabolism, especially when the
      oxygen consumption rate is increased above 1.2-1.3 l/min. The model ascribes the
      poor response to exercise in these patients to the incapacity to sustain venous
      return caused by the high resistance to venous return and/or to exhaustion of
      volume compensation reserve.

PMID- 11834501
TI  - Cardiac myocyte adenosine A2a receptor activation fails to alter cAMP or
      contractility: role of receptor localization.
AB  - Adenosine A2a receptors are found in coronary vascular tissue although, their
      presence in myocardium is subject to investigation. Although there have been
      numerous studies on adenosine A2a receptor agonist effects on contractility and
      cAMP levels in ventricular myocytes, these have yielded conflicting results.
      Negative pharmacological studies have even led to the conclusion that A2a
      receptors are not present in cardiac myocytes. The purpose of this study was to
      determine whether A2a receptors are expressed in rat ventricular myocytes and
      what physiological effects are mediated via activation of these receptors.
      Western blot analysis with a polyclonal antibody raised against a peptide
      sequence specific to the carboxy terminus of the A2a receptor revealed the
      presence of a band at approximately 45 kDa. However, the immunoreactivity was
      located in the nonmembrane fraction of the cell lysate. The membrane fraction
      only exhibited an immunoreactive band > or = 50 kDa. Treatment of isolated
      myocytes with the adenosine A2a agonist 2-[4-[(2-carboxyethyl)-phenyl]ethylamino]
      5'-N-ethylcarboxamidoadenosine (CGS-21680) exerted no effects on cAMP levels or
      myocyte twitch amplitude. These results indicate that although rat ventricular
      myocytes appear to express adenosine A2a receptors, stimulation with an A2a
      agonist exerts no functional effects, possibly because of the subcellular
      localization of the A2a receptor.

PMID- 11834502
TI  - Relation of effective arterial elastance to arterial system properties.
AB  - Effective arterial elastance (E(a)), defined as the ratio of left ventricular
      (LV) end-systolic pressure and stroke volume, lumps the steady and pulsatile
      components of the arterial load in a concise way. Combined with E(max), the slope
      of the LV end-systolic pressure-volume relation, E(a)/E(max) has been used to
      assess heart-arterial coupling. A mathematical heart-arterial interaction model
      was used to study the effects of changes in peripheral resistance (R; 0.6-1.8
      mmHg x ml(-1) x s) and total arterial compliance (C; 0.5-2.0 ml/mmHg) covering
      the human pathophysiological range. E(a), E(a)/E(max,) LV stroke work, and
      hydraulic power were calculated for all conditions. Multiple-linear regression
      analysis revealed a linear relation between E(a), R/T (where T is cycle length),
      and 1/C: E(a) = -0.13 + 1.02R/T + 0.31/C, indicating that R/T contributes about
      three times more to E(a) than arterial stiffness (1/C). It is demonstrated that
      different pathophysiological combinations of R and C may lead to the same E(a)
      and E(a)/E(max) but can result in differences of 10% in stroke work and 50% in
      maximal power.

PMID- 11834503
TI  - Modulation of action potential by [Ca2+]i in modeled rat atrial and guinea pig
      ventricular myocytes.
AB  - We simulated mechanisms that increase Ca2+ transients with two models: the Luo
      Rudy II model for guinea pig (GP) ventricle (GP model) representing long action
      potential (AP) myocytes and the rat atrial (RA) model exemplifying myocytes with
      short APs. The interventions were activation of stretch-gated cationic channels,
      increase of intracellular Na+ concentration ([Na+]i), simulated bet-adrenoceptor
      stimulation, and Ca2+ accumulation into the sarcoplasmic reticulum (SR). In the
      RA model, interventions caused an increase of AP duration. In the GP model, AP
      duration decreased except in the simulated beta-stimulation where it lengthened
      APs as in the RA model. We conclude that the changes in the APs are significantly
      contributed by the increase of the Ca2+ transient itself. The AP duration is
      controlled differently in cardiac myocytes with short and long AP durations. With
      short APs, an increase of the Ca2+ transient promotes an inward current via
      Na+/Ca2+-exchanger lengthening the AP. This effect is similar regardless of the
      mechanism causing the increase of the Ca2+ transient. With long APs the Ca2+
      transient increase decreases the AP duration via inactivation of the L-type Ca2+
      current. However, L-type current increase (as with beta-stimulation) increases
      the AP duration despite the simultaneous Ca2+ transient augmentation. The results
      explain the dispersion of AP changes in myocytes with short and long APs during
      interventions increasing the Ca2+ transients.

PMID- 11834504
TI  - Cooperative activation in cardiac muscle: impact of sarcomere length.
AB  - This study was undertaken to determine the impact of sarcomere length (SL) on the
      level of cooperative activation of the cardiac myofilament at physiological
      [Mg2+]. Active force development was measured in skinned rat cardiac trabeculae
      as a function of free [Ca2+] at five SLs (1.85-2.25 microm; 1 mM free [Mg2+]; 15
      degrees C). Only muscle preparations with minimal force rundown during the entire
      protocol were included in the analysis (average 7.2 +/- 1.7%). Median SL was
      measured by on-line computer video micrometry and controlled within 0.01 microm.
      Care was taken to ensure a sufficient number of data points in the steep portion
      of the [Ca2+]-force relationship at every SL to allow for accurate fit of the
      data to a modified Hill equation. Multiple linear regression analysis of the fit
      parameters revealed that both maximum, Ca2+-saturated force and Ca2+ sensitivity
      were a significant function of SL (P < 0.001), whereas the level of cooperativity
      did not depend on SL (P = 0.2). Further analysis of the [Ca2+]-force
      relationships revealed a marked asymmetry that, also, was not affected by SL (P =
      0.2-0.6). Finally, we found that the level of cooperativity in isolated skinned
      myocardium was comparable to that reported for intact, nonskinned myocardium. Our
      results suggest that an increase in SL induces an increase in the Ca2+
      responsiveness of the cardiac sarcomere without affecting the level of
      cooperativity.

PMID- 11834505
TI  - Effects of amiodarone on wave front dynamics during ventricular fibrillation in
      isolated swine right ventricle.
AB  - The effects of acute amiodarone infusion on dynamics of ventricular fibrillation
      (VF) are unclear. Six isolated swine right ventricles (RVs) were studied in
      vitro. Activation patterns during VF were mapped optically, whereas action
      potentials were recorded with a glass microelectrode. At baseline, VF was
      associated with frequent spontaneous wave breaks. Amiodarone (2.5 microg/ml)
      reduced spontaneous wave breaks and increased the cycle length (CL) of VF from
      83.3 +/- 17.8 ms at baseline to 118.4 +/- 25.8 ms during infusion (P < 0.05).
      Amiodarone increased the reentrant wave front CL (114.4 +/- 15.5 vs. 78.2 +/-
      19.0 ms, P < 0.05) and central core area (4.1 +/- 3.8 vs. 0.9 +/- 0.3 mm2, P <
      0.05). Within 30 min of infusion, VF terminated (n = 1), converted to ventricular
      tachycardia (VT) (n = 1) or continued at a slower rate (n = 4). Amiodarone
      flattened the APD restitution curves. We conclude that amiodarone reduced
      spontaneous wave breaks. It might terminate VF or convert VF to VT. These effects
      were associated with the flattening of APD restitution slope and increased core
      size of reentrant wave fronts.

PMID- 11834506
TI  - Acute protection of ischemic heart by FGF-2: involvement of FGF-2 receptors and
      protein kinase C.
AB  - We examined the effect of fibroblast growth factor (FGF)-2 on myocardial
      resistance to injury when administered after the onset of ischemia, in vivo and
      ex vivo, and the role of FGF-2 receptors and protein kinase C (PKC). FGF-2 was
      injected into the left ventricle of rats undergoing permanent surgical coronary
      occlusion leading to myocardial infarction (MI). After 24 h, FGF-2-treated hearts
      displayed significantly reduced injury, determined by histological staining and
      troponin T release, and improved developed pressure compared with untreated
      controls. An FGF-2 mutant with diminished affinity for the tyrosine kinase FGF-2
      receptor 1 (FGFR1) was not cardioprotective. FGF-2-treated hearts retained
      improved function and decreased damage at 6 wk after MI. In the ex vivo heart,
      FGF-2 administration during reperfusion after 30-min ischemia improved functional
      recovery and increased relative levels of PKC subtypes alpha, epsilon, and zeta
      in the particulate fraction, in a chelerythrine-preventable mode; it also
      decreased loss of energy metabolites. We conclude that intramyocardial FGF-2
      administration shortly after the onset of ischemia confers protection from acute
      and chronic cardiac dysfunction and damage; FGF-2 delivered during reperfusion
      protects from ischemia-reperfusion injury; and protection by FGF-2 requires
      intact binding to FGFR1 and is likely mediated by PKC.

PMID- 11834507
TI  - Load dependence of ventricular performance explained by model of calcium
      myofilament interactions.
AB  - Although a simple concept of load-independent behavior of the intact heart
      evolved from early studies of isolated, intact blood-perfused hearts, more recent
      studies showed that, as in isolated muscle, the mode of contraction (isovolumic
      vs. ejection) impacts on end-systolic elastance. The purpose of the present study
      was to test whether a four-state model of myofilament interactions with length
      dependent rate constants could explain the complex contractile behavior of the
      intact, ejecting heart. Studies were performed in isolated, blood-perfused canine
      hearts with intracellular calcium transients measured by macroinjected aequorin.
      Measured calcium transients were used as the driving function for the model, and
      length-dependent rate constants yielding the highest concordance between measured
      and model-predicted midwall stress at different isovolumic volumes were
      determined. These length-dependent rate constants successfully predicted
      contractile behavior on ejecting contractions. This, along with additional model
      analysis, suggests that length-dependent changes in calcium binding affinity may
      not be an important factor contributing to load-dependent contractile performance
      in the intact heart under physiological conditions.

PMID- 11834508
TI  - Temperature-sensitive intracellular Mg2+ block of L-type Ca2+ channels in cardiac
      myocytes.
AB  - We examined the concentration-dependent blocking effects of intracellular Mg2+ on
      L-type Ca2+ channels in cardiac myocytes using the whole cell patch-clamp
      technique. The increase of L-type Ca2+ channel current (I(Ca)) (due to relief of
      Mg2+ block) occurred in two temporal phases. The rapid phase (runup) transiently
      appeared early (<5 min) in dialysis of the low-Mg2+ solution; the slow phase
      began later in dialysis (>10 min). Runup was not blocked by intracellular GTP
      (GTP(i)). The late phase of the I(Ca) increase (late I(Ca)) was suppressed by
      GTP(i) (0.4 mM) and was observed in myocytes of the guinea pig or frog at higher
      (32 or 24 degrees C, respectively) rather than lower temperatures (24 or 17.5
      degrees C, respectively). At pMg = 6.0, raising the temperature from 24 to 32
      degrees C evoked late I(Ca) with a Q10 of 14.5. Restoring the temperature to 24
      degrees C decreased I(Ca) with a Q10 of only 2.4. The marked difference in the
      Q10 values indicated that late I(Ca) (pMg = 5-6) is an irreversible phenomenon.
      Phosphorylation suppressed the intracellular [Mg2+] dependency of late I(Ca).
      This effect of phosphorylation together with the inhibitory action of GTP(i) on
      Mg2+-dependent blocking of I(Ca) are common properties of mammalian and amphibian
      cardiomyocytes.

PMID- 11834509
TI  - Optimal ventricular rate slowing during atrial fibrillation by feedback AV nodal
      selective vagal stimulation.
AB  - Although the beneficial effects of ventricular rate (VR) slowing during atrial
      fibrillation (AF) are axiomatic, the precise relationship between VR and
      hemodynamics has not been determined. We hypothesized that selective
      atrioventricular node (AVN) vagal stimulation (AVN-VS) by varying the nerve
      stimulation intensity could achieve precise graded slowing and permit evaluation
      of an optimal VR during AF. The aims of the present study were the following: 1)
      to develop a method for computerized vagally controlled VR slowing during AF, 2)
      to determine the hemodynamic changes at each level of VR slowing, and 3) to
      establish the optimal anterograde VR during AF. AVN-VS was delivered to the
      epicardial fat pad that projects parasympathetic nerve fibers to the AVN in 14
      dogs. Four target average VR levels, corresponding to 75%, 100%, 125%, and 150%
      of the sinus cycle length (SCL), were achieved by computer feedback algorithm. VR
      slowing resulted in improved hemodynamics and polynomial fit analysis found an
      optimum for the cardiac output at VR slowing of 87% SCL. We conclude that this
      novel method can be used to maintain slow anterograde conduction with best
      hemodynamics during AF.

PMID- 11834510
TI  - Nitric oxide modulates endotoxin-induced platelet-endothelial cell adhesion in
      intestinal venules.
AB  - Although platelets have been implicated in the pathogenesis of vascular diseases,
      little is known about factors that regulate interactions between platelets and
      the vessel wall under physiological conditions. The objectives of this study were
      to 1) define the contribution of nitric oxide (NO) to endotoxin
      (lipopolysaccharide, LPS)-induced platelet-endothelial cell (P/E) adhesion in
      murine intestinal venules and 2) determine whether the antiadhesive action of NO
      is mediated by soluble guanylate cyclase (sGC). Adhesive interactions between
      platelets and endothelial cells were monitored by intravital microscopy. LPS
      administration into control wild-type mice (WT) resulted in a >15-fold increase
      in P/E adhesion. Similar responses were observed using endothelial NO synthase
      (eNOS)-deficient platelets. However, treatment with the NO donor
      diethylenetriamine-nitric oxide (DETA-NO) attenuated the P/E adhesion response to
      LPS, whereas the NO synthase inhibitor N(G)-nitro-L-arginine methyl ester or eNOS
      deficiency resulted in an exacerbation. P/E adhesion response did not differ
      between LPS-treated WT and inducible NOS-deficient mice. Inhibition of sGC
      abolished the attenuating effects of DETA-NO, whereas the sGC activator 3-(5'
      hydroxymethyl-2'-furyl)-1-benzyl indazole (YC-1) reduced LPS-induced P/E
      adhesion. These findings indicate that 1) eNOS-derived NO attenuates endotoxin
      induced P/E adhesion and 2) sGC is responsible for the antiadhesive action of NO.

PMID- 11834511
TI  - Activation of cardiac ryanodine receptors by cardiac glycosides.
AB  - This study investigated the effects of cardiac glycosides on single-channel
      activity of the cardiac sarcoplasmic reticulum (SR) Ca2+ release channels or
      ryanodine receptor (RyR2) channels and how this action might contribute to their
      inotropic and/or toxic actions. Heavy SR vesicles isolated from canine left
      ventricle were fused with artificial planar lipid bilayers to measure single RyR2
      channel activity. Digoxin and actodigin increased single-channel activity at low
      concentrations normally associated with therapeutic plasma levels, yielding a 50%
      of maximal effect of approximately 0.2 nM for each agent. Channel activation by
      glycosides did not require MgATP and occurred only when digoxin was applied to
      the cytoplasmic side of the channel. Similar results were obtained in human RyR2
      channels; however, neither the crude skeletal nor the purified cardiac channel
      was activated by glycosides. Channel activation was dependent on [Ca2+] on the
      luminal side of the bilayer with maximal stimulation occurring between 0.3 and 10
      mM. Rat RyR2 channels were activated by digoxin only at 1 microM, consistent with
      the lower sensitivity to glycosides in rat heart. These results suggest a model
      in which RyR2 channel activation by digoxin occurs only when luminal [Ca2+] was
      increased above 300 microM (in the physiological range). Consequently, increasing
      SR load (by Na+ pump inhibition) serves to amplify SR release by promoting direct
      RyR2 channel activation via a luminal Ca2+-sensitive mechanism. This high
      affinity effect of glycosides could contribute to increased SR Ca2+ release and
      might play a role in the inotropic and/or toxic actions of glycosides in vivo.

PMID- 11834512
TI  - Natriuretic peptide gene expression in DOCA-salt hypertension after blockade of
      type B endothelin receptor.
AB  - We investigated the effect of long-term in vivo blockade of the ET-1 receptor
      subtype B (ET(B)) with A-192621, a selective ET(B) antagonist, on atrial and
      ventricular natriuretic peptide (NP) gene expression in deoxycorticosterone
      acetate (DOCA)-salt hypertension. In this model, stimulation of the cardiac
      natriuretic peptide (NP) and the endothelin system and suppression of the renin
      angiotensin system is observed. DOCA-salt induced significant hypertension,
      cardiac hypertrophy and increased NP plasma and left atrial and right and left
      ventricular NP gene expression. ET(B) blockade per se produced hypertension and
      left ventricular hypertrophy but induced little change on the levels of
      ventricular NP and only increased left atrial natriuretic factor (ANF) mRNA
      levels. Combined ET(B) blockade/DOCA-salt treatment worsened hypertension,
      increased left ventricular hypertrophy and induced right ventricular hypertrophy.
      All animals so treated had increased ventricular NP gene expression. Collagen III
      and beta-myosin heavy chain gene expression were enhanced in both the right and
      the left ventricle of DOCA-salt hypertensive rats. The results of this study
      suggest that the ET(B) receptor does not participate directly in the modulation
      of atrial or ventricular NP gene expression and that this receptor mediates a
      protective cardiovascular function. ET(B) blockade can induce significant
      ventricular hypertrophy without an increase in ANF or brain NP gene expression.

PMID- 11834513
TI  - Aortic leucine-to-glutamate pathway: metabolic route and regulation of
      contractile responses.
AB  - Rat aortic endothelium is differentiated regionally for three signal pathways
      capable of regulating the cGMP content of the underlying smooth muscle. Formation
      of nitric oxide (NO) from L-arginine and of glutamate from L-leucine increase
      cGMP; however, formation of prostaglandin H2 (PGH2) decreases cGMP. All three
      have peak activity in the windkessel area just distal to the aortic arch and
      decrease peripherally. We report evidence that the biochemical route of the
      leucine-to-glutamate (Leu-->Glu) pathway is via metabolism of leucine to acetyl
      CoA, that the controlling reaction of the pathway is mediated by the branched
      chain alpha-ketoacid dehydrogenase complex (BCDC), and that glutamate formation
      via the Leu-->Glu pathway is a major source of aortic segment free glutamate in
      vitro. Interruption of the pathway by treatment of precontracted rat aortic rings
      in vitro with each of three classes of inhibitors (leucine analogs, competitors
      for the BCDC reaction, or inhibitors of L-glutamate transport) enhances
      contractile responses. The enhancement requires an intact endothelium and is not
      owing to reductions in NO formation. The results support the hypothesis that the
      Leu-->Glu pathway functions in the regulation of aortic contractility and
      compliance.

PMID- 11834514
TI  - High-cut characteristics of the baroreflex neural arc preserve baroreflex gain
      against pulsatile pressure.
AB  - A transfer function from baroreceptor pressure input to sympathetic nerve
      activity (SNA) shows derivative characteristics in the frequency range below 0.8
      Hz in rabbits. These derivative characteristics contribute to a quick and stable
      arterial pressure (AP) regulation. However, if the derivative characteristics
      hold up to heart rate frequency, the pulsatile pressure input will yield a
      markedly augmented SNA signal. Such a signal would saturate the baroreflex signal
      transduction, thereby disabling the baroreflex regulation of AP. We hypothesized
      that the transfer gain at heart rate frequency would be much smaller than that
      predicted from extrapolating the derivative characteristics. In anesthetized
      rabbits (n = 6), we estimated the neural arc transfer function in the frequency
      range up to 10 Hz. The transfer gain was lost at a rate of -20 dB/decade when the
      input frequency exceeded 0.8 Hz. A numerical simulation indicated that the high
      cut characteristics above 0.8 Hz were effective to attenuate the pulsatile signal
      and preserve the open-loop gain when the baroreflex dynamic range was finite.

PMID- 11834515
TI  - Staphylococcal alpha-toxin provokes neutrophil-dependent cardiac dysfunction:
      role of ICAM-1 and cys-leukotrienes.
AB  - The role of polymorphonuclear neutrophils (PMN) in septic myocardial dysfunction
      is presently unknown. Staphylococcus aureus infections are frequently associated
      with septic sequelae. Therefore, we perfused isolated rat hearts with low doses
      of alpha-toxin, the major staphylococcal exotoxin, followed by application of
      human PMN, N-formyl-methionyl-leucyl-phenylalanine, and arachidonic acid. In
      contrast to sham-perfused hearts (no alpha-toxin), a rise in coronary perfusion
      pressure (CPP) and a reduction of contractile function were noted, and cardiac
      expression of intercellular adhesion molecule (ICAM)-1 was detected by
      immunohistochemical methods and real-time PCR. Histological analysis and
      myeloperoxidase activity indicated cardiac PMN accumulation in alpha-toxin
      challenged hearts. Major quantities of cysteinyl (cys)-leukotrienes (LT), LTB4,
      and 5-hydroxyeicosatetraenoic acid (5-HETE) were found in the perfusate of alpha
      toxin-exposed hearts. With an anti-ICAM-1 antibody, neutrophil accumulation,
      leukotriene (LT) synthesis, coronary vasoconstriction, and the accompanying
      cardiodepression were suppressed. Similarly, the lipoxygenase inhibitor MK-886
      blocked LT synthesis and maintained cardiac function. We conclude that low-dose
      alpha-toxin provokes coronary endothelial ICAM-1 expression and neutrophil
      accumulation, with subsequent synthesis of cys-LTs, LTB4, and 5-HETE under
      conditions of appropriate stimulation. This response is linked with coronary
      vasoconstriction and contractile dysfunction, with cys-LT synthesis and
      maldistribution of perfusion offered as likely underlying mechanisms.

PMID- 11834516
TI  - Molecular conformation dictates signaling module formation: example of PKCepsilon
      and Src tyrosine kinase.
AB  - Our laboratory has conducted multiple functional proteomic analyses to
      characterize the components of protein kinase C (PKC)epsilon cardioprotective
      signaling complexes and found that activation of PKCepsilon induces dynamic
      modulation of these complexes. In addition, it is known that signal transduction
      within a complex involves the formation of modules, one of which has been shown
      to include PKCepsilon and Src tyrosine kinase in the rabbit heart. However, the
      cellular mechanisms that define the assembly of PKCepsilon modules remain largely
      unknown. To address this issue, the interactions between PKCepsilon and Src were
      studied. We used recombinant proteins of wild-type PKCepsilon (PKCepsilon-WT) and
      open conformation mutants of the kinase (PKCepsilon-AE5 and PKCepsilon-AN59), the
      regulatory and catalytic domains of PKCepsilon, along with glutathione-S
      transferase (GST) fusion proteins of Src (GST-Src) and two domains of Src (GST
      SH2 and GST-SH3). GST pulldown assays demonstrated that Src and PKCepsilon are
      binding partners and that the interaction between PKCepsilon and Src appears to
      involve multiple sites. This finding was supported for endogenous PKCepsilon and
      Src in the murine heart using immunofluorescence-based confocal microscopy and
      coimmunoprecipitation. Furthermore, PKCepsilon-WT and GST-Src interactions were
      significantly enhanced in the presence of phosphatidyl-L-serine, an activator of
      PKC, indicating that Src favors interaction with activated PKCepsilon. This
      finding was confirmed when the PKCepsilon-WT was replaced with PKCepsilon-AE5 or
      PKCepsilon-AN59, demonstrating that the conformation of PKCepsilon is a critical
      determinant of its interactions with Src. Together, these results illustrate that
      formation of a signaling module between PKCepsilon and Src involves specific
      domains within the two molecules and is governed by the molecular conformation of
      PKCepsilon.

PMID- 11834517
TI  - Female hormones and thrombosis.
AB  - Exogenous hormones are used by more than a hundred million women worldwide as
      oral contraceptives or for postmenopausal hormone replacement. Oral
      contraceptives increase the risk of venous thrombosis, of myocardial infarction,
      and of stroke. The risk is highest during the first year of use. The venous
      thrombotic risk of oral contraceptives is high among women with coagulation
      abnormalities and with so-called third-generation contraceptives (containing
      desogestrel or gestodene). The risk of myocardial infarction does not appear to
      depend on coagulation abnormalities or the type of oral contraceptive. Hormone
      replacement therapy increases the risk of venous thrombosis. This risk is also
      highest in the first year of use and among women with coagulation abnormalities.
      The risk becomes very high in women with a previous venous thrombosis. Randomized
      trials have not confirmed a beneficial effect of postmenopausal hormones on the
      occurrence of myocardial infarction.

PMID- 11834518
TI  - Lipoprotein lipase in the arterial wall: linking LDL to the arterial
      extracellular matrix and much more.
AB  - For low density lipoprotein (LDL) particles to be atherogenic, increasing
      evidence indicates that their residence time in the arterial intima must be
      sufficient to allow their modification into forms capable of triggering
      extracellular and intracellular lipid accumulation. Recent reports have confirmed
      the longstanding hypothesis that the major determinant(s) of initial LDL
      retention in the preatherosclerotic arterial intima is the proteoglycans.
      However, once the initial atherosclerotic lesions have formed, a shift to
      retention facilitated by macrophage-derived lipoprotein lipase (LPL) appears,
      leading to the progression of the lesions. Here, we review recent findings on the
      mechanisms enabling LPL to promote LDL retention and extracellular lipid
      accumulation in the arterial intima, and we describe the structures in the
      extracellular matrix that are held to be important in this process. Finally, the
      potentially harmful consequences of LDL linking by LPL and of other LPL actions
      in the arterial intima are briefly reviewed.

PMID- 11834519
TI  - Expression and localization of tissue factor pathway inhibitor-2 in normal and
      atherosclerotic human vessels.
AB  - Tissue factor pathway inhibitor-2 (TFPI-2) is a Kunitz-type, serine protease
      inhibitor with inhibitory activity toward activated factor XI, plasma kallikrein,
      plasmin, certain matrix metalloproteinases, and the tissue factor:activated
      factor VII complex. In this study, we investigated TFPI-2 expression and
      localization in normal and atherosclerotic human arteries by using in situ
      hybridization and immunohistochemical techniques. In healthy human blood vessels,
      TFPI-2 was detected in the vascular endothelium alone. In human atherosclerotic
      tissues, TFPI-2 expression was assigned to macrophages, T cells, endothelial
      cells, and smooth muscle cells. Western blot analysis for TFPI-2 confirmed its
      production by cultured human aortic smooth muscle cells, U937 cells (monocytes),
      and Jurkat (T cell) cell lines. Reverse transcription-polymerase chain reaction
      revealed similar TFPI-2 expression levels in both monocytes and macrophages in
      culture. Electron microscopic study with immunogold labeling revealed the
      association of TFPI-2 antigen with both the extracellular matrix and plasma
      membranes. TFPI-2 antigen was detected in some areas of atheroma that also
      stained positively for both tissue factor and factor VII. Moreover, detection of
      TFPI-2 in close spatial proximity to plasmin/plasminogen on macrophages, on
      endothelial cells, and in matrix-rich areas highlighted its possible functional
      significance in the regulation of plasmin activity and downstream proteolytic
      mechanisms that occur in the atherosclerotic lesion.

PMID- 11834520
TI  - Altered pattern of vascular connexin expression in atherosclerotic plaques.
AB  - Paracrine cell-to-cell interactions are crucial events during atherogenesis.
      However, little is known about the role of direct intercellular communication via
      gap junctions during this process. We have investigated the expression pattern of
      3 vascular gap junction proteins (connexins) in mouse and human atherosclerotic
      plaques. Low density lipoprotein receptor-deficient mice were fed a high-fat diet
      for 0, 6, 10, or 14 weeks to induce different stages of atherosclerosis.
      Connexin37 (Cx37) and Cx40 were detected in the endothelium, and Cx43 was
      detected in the media of nondiseased aortas. In early atheromas, endothelial and
      medial connexin expression remained unchanged, and "islets" of Cx43 in smooth
      muscle cells and Cx37 in macrophages were observed in the neointima. In advanced
      atheromas, Cx37 was detected in medial smooth muscle cells and in macrophages in
      the lipid core but not in the endothelium covering the plaques. Cx40 could also
      no longer be detected in the endothelium covering the plaques. Cx43, on the other
      hand, was detected in the endothelium covering the shoulder of the plaques and
      also sparsely in neointimal smooth muscle cells. Similar results were obtained
      for human carotid arteries. In conclusion, vascular connexins are differentially
      expressed by atheroma-associated cells within lesions. These observations suggest
      a role for gap junctional intercellular communication during atherogenesis.

PMID- 11834521
TI  - Identification of a zinc finger homoeodomain enhancer protein after AT(2)
      receptor stimulation by differential mRNA display.
AB  - Using differential mRNA display, we isolated differentially expressed genes after
      stimulation of angiotensin II (Ang II) type 2 (AT(2)) receptors in PC12w cells.
      Among the polymerase chain reaction products isolated, we identified Zfhep, a
      zinc finger homoeodomain enhancer-binding protein and the angiotensin AT(2)
      receptor itself, both implicated in developmental processes. In the presence of
      epidermal growth factor (EGF) a concordant expression pattern of Zfhep and AT(2)
      mRNA was observed with marked downregulation 6 hours after stimulation with
      EGF+Ang II. In quiescent PC12w cells, Zfhep mRNA was time-dependently induced by
      Ang II (10(-7) mol/L) up to 3 hours, an effect that was blocked by the selective
      AT(2) antagonist PD123177 (10(-6) mol/L). We extended our studies on Zfhep mRNA
      expression to cells of vascular origin (coronary endothelial cells [CECs]), that
      express AT(1) and AT(2) receptors, and that respond differently to Ang II
      dependent on which receptor subtype is stimulated. In CECs, Zfhep mRNA expression
      was induced up to 3 hours after AT(2) stimulation. Interestingly, this Zfhep
      induction was observed only when the AT(1) receptor was blocked by using the
      selective AT(1) receptor antagonist, losartan (10(-5) mol/L), suggesting a
      negative-regulatory influence of AT(1) receptors on AT(2)-induced Zfhep mRNA
      induction. In conclusion, Zfhep not only represents a suitable marker for AT(2)
      receptor activation, but it may also link AT(2) signaling and downstream events
      involved in the proposed function of the AT(2) receptor in development and
      regeneration.

PMID- 11834522
TI  - Tumor necrosis factor-alpha inhibits growth factor-mediated cell proliferation
      through SHP-1 activation in endothelial cells.
AB  - Src homology 2-containing protein-tyrosine phosphatase 1 (SHP-1) is known to
      regulate signal transduction through the dephosphorylation of tyrosine kinases.
      In this study, we addressed the role of SHP-1 under tumor necrosis factor-alpha
      (TNF-alpha) stimulation in endothelial cells. The addition of recombinant
      vascular endothelial growth factor (50 ng/mL) or epidermal growth factor (50
      ng/mL) significantly increased thymidine incorporation and c-fos promoter
      activity, whereas TNF-alpha (5 ng/mL) attenuated these effects in human or bovine
      aortic endothelial cells. In bovine aortic endothelial cells, we confirmed
      endogenous SHP-1 expression and that TNF-alpha activated SHP-1. Importantly,
      overexpression of dominant-negative SHP-1 attenuated the effect of TNF-alpha on
      thymidine incorporation and c-fos promoter activity. In addition, TNF-alpha
      attenuated vascular endothelial growth factor- and epidermal growth factor
      induced extracellular signal-regulated kinase phosphorylation, whereas
      overexpression of dominant-negative SHP-1 prevented this inhibitory effect of TNF
      alpha. Taken together, our results suggested that TNF-alpha inhibited growth
      factor-mediated cell proliferation through SHP-1 activation.

PMID- 11834523
TI  - Involvement of rho-kinase in agonists-induced contractions of arteriosclerotic
      human arteries.
AB  - Coronary artery spasm plays an important role in the pathogenesis of a wide
      variety of ischemic heart diseases. We have recently demonstrated that Rho-kinase
      plays a key role in the spasm in our porcine model. However, it remains to be
      elucidated whether Rho-kinase-mediated pathway also contributes to
      vasoconstriction of human arteries. From 15 patients who underwent coronary
      artery bypass operation, segments of isolated left internal thoracic arteries
      were obtained, and the endothelium was gently removed. Serotonin and histamine
      caused contractions, which were markedly inhibited by a specific Rho-kinase
      inhibitor, hydroxyfasudil. Western blot analysis showed that, during the
      serotonin-induced contractions, the extent of phosphorylation of myosin-binding
      subunit of myosin phosphatase (MBS, one of the major substrates of Rho-kinase)
      was significantly increased in the specimens. Hydroxyfasudil again significantly
      suppressed the serotonin-induced increase in MBS phosphorylation. There was a
      significant positive correlation between the extent of MBS phosphorylation and
      that of the serotonin-induced contractions and between hydroxyfasudil-sensitive
      components of the contractions and the extent of arteriosclerosis. These results
      indicate that Rho-kinase plays an important role in vascular smooth muscle
      contractions of arteriosclerotic human arteries, suggesting that Rho-kinase could
      be regarded as an important target for the treatment of arteriosclerotic vascular
      diseases in humans.

PMID- 11834524
TI  - Gene transfer of endothelial NO synthase and manganese superoxide dismutase on
      arterial vascular cell adhesion molecule-1 expression and superoxide production
      in deoxycorticosterone acetate-salt hypertension.
AB  - Enhanced vascular cell adhesion molecule-1 (VCAM-1) expression directly
      contributes to vascular dysfunction in hypertension. Decreased NO and/or
      increased superoxide are causative factors for such an event in the vessel wall.
      The present study was undertaken to determine whether gene transfer of
      endothelial NO synthase (eNOS) or manganese superoxide dismutase (MnSOD) affects
      VCAM-1 levels in arteries from hypertensive rats. Isolated carotid and femoral
      arteries from deoxycorticosterone acetate (DOCA)-salt hypertensive rats were
      transduced for 4 hours with adenoviral vectors encoding eNOS, MnSOD, or beta
      galactosidase reporter genes. Recombinant eNOS or MnSOD expression was evident
      morphologically and quantitatively 24 hours after gene transfer.
      Immunohistochemistry, ELISA, and Western blot techniques were used to determine
      VCAM-1 expression and levels. In addition, endogenous eNOS and MnSOD and in situ
      superoxide levels were analyzed by immunoblotting and fluorescence confocal
      microscopy, respectively. Arterial VCAM-1 expression was significantly higher in
      DOCA-salt hypertensive rats than in sham-operated rats; this expression was
      accompanied by decreased MnSOD but unaltered endogenous eNOS levels. VCAM-1
      expression was significantly lower in MnSOD- and eNOS-transduced hypertensive
      arteries, with a concomitant reduction of superoxide level. These results suggest
      that gene transfer of MnSOD or eNOS suppresses arterial VCAM-1 expression in DOCA
      salt hypertension by reducing the superoxide level.

PMID- 11834525
TI  - Prostacyclin synthase gene transfer modulates cyclooxygenase-2-derived prostanoid
      synthesis and inhibits neointimal formation in rat balloon-injured arteries.
AB  - Previous studies have shown that prostacyclin (PGI(2)) synthase (PCS) gene
      transfer inhibits neointimal formation in balloon-injured arteries. However, the
      role of each cyclooxygenase (COX) isoform in this healing mechanism remains
      unknown. We hypothesized that overexpression of PCS may modulate COX-2-mediated
      prostaglandin (PG) metabolism. That is to say, excessive PGH(2) derived from COX
      2 after balloon injury may be converted into PGI(2) rather than PGE(2) or
      thromboxane (TX) A(2) by overexpressed PCS. We examined the expression of COX
      isoforms and evaluated the role of COX-2 with regard to the effects of PCS gene
      transfer by using 4-(4-cyclohexyl-2-methyloxazol-5-yl)-2-fluorobenzenesulfonamide
      (JTE-522), a selective COX-2 inhibitor. Rats were divided into 4 groups in
      conjunction with PCS gene transfer and JTE-522 treatment. The PCS gene (30
      microg) was transfected into rat balloon-injured arteries by a lipotransfection
      method. JTE-522 (30 mg/kg per day) was administered for 14 days after balloon
      injury. Immunohistochemical analysis demonstrated marked COX-2 expression on the
      neointima. PCS gene transfer markedly inhibited neointimal formation, but JTE-522
      reversed this beneficial effect. PCS gene transfer augmented PGI(2) production
      and decreased PGE(2) production without affecting TXA(2) production, but JTE-522
      inhibited this increase in PGI(2) production. In conclusion, PCS gene transfer
      modulated COX-2-mediated prostanoid synthesis and inhibited neointimal formation
      after balloon injury.

PMID- 11834526
TI  - Beneficial effects of NO-releasing derivative of flurbiprofen (HCT-1026) in rat
      model of vascular injury and restenosis.
AB  - One of the major problems related to the percutaneous transluminal coronary
      angioplasty technique is the renarrowing of the vessel, a phenomenon known as
      restenosis. NO and nonsteroidal anti-inflammatory drugs have been shown to play a
      role in this pathology. The main problem with the use of conventional NO donors
      is that they affect blood pressure and flow, and for these reasons, they cannot
      be used safely in clinical practice. The aim of this study was to evaluate, with
      the use of a rat model of balloon angioplasty, whether a structural derivative of
      flurbiprofen, containing an added NO-releasing moiety (HCT-1026), is able to
      reduce or prevent neointimal formation. Rats were treated for 14 days with
      equimolar doses of flurbiprofen (2, 7, and 21 mg/kg) or HCT-1026 (3, 10, and 30
      mg/kg). After this 14-day treatment, HCT-1026 but not flurbiprofen significantly
      modified the neointima/media ratio. The reduction in the neointimal proliferation
      obtained with HCT-1026 was well correlated with an increase in nitrite/nitrate
      plasma levels and a reduced cell proliferation. Neither HCT-1026 nor flurbiprofen
      affected inducible NO synthase induction in injured vessels. In conclusion, HCT
      1026 caused a significant reduction in restenosis that appears to be directly
      related to NO release. HCT-1026 may prove to be beneficial in preventing or
      delaying restenosis in humans.

PMID- 11834527
TI  - Activated mast cells increase the level of endothelin-1 mRNA in cocultured
      endothelial cells and degrade the secreted Peptide.
AB  - Subendothelial mast cells have been implicated in the pathogenesis of allergic
      inflammation, in atherosclerosis, and in the regulation of vascular tone. Because
      endothelin-1 (ET-1) is an important regulator of vascular tone and has also been
      implicated in the pathogenesis of atherosclerosis, we studied the role of mast
      cells in the metabolism of endothelial cell-derived ET-1. In mast cell
      endothelial cell cocultures, activation of the mast cells with ensuing
      degranulation was accompanied by the increased expression of ET-1 mRNA in the
      endothelial cells, yet the immunoreactive ET-1 protein in the coculture medium
      disappeared almost completely during the 24-hour coculture. Activation of the
      mast cells with the ensuing degranulation resulted in proteolytic degradation of
      ET-1 by the 2 neutral proteases, chymase and carboxypeptidase A, of the
      exocytosed mast cell granules. With synthetic ET-1 and purified mast cell granule
      enzymes, efficient degradation of ET-1 by chymase and carboxypeptidase A was
      verified. These in vitro results imply a novel role for mast cell-derived neutral
      proteases in ET-1 metabolism and suggest that activated subendothelial mast cells
      are important local regulators of ET-1 metabolism.

PMID- 11834528
TI  - Diagnosis of familial combined hyperlipidemia based on lipid phenotype expression
      in 32 families: results of a 5-year follow-up study.
AB  - Familial combined hyperlipidemia (FCH) is characterized by a variable expression
      of hypercholesterolemia and/or hypertriglyceridemia. We evaluated the variability
      in lipid phenotype expression over a 5-year period and studied factors affecting
      the lipid phenotype expression. A total of 32 families (299 subjects) were
      studied in 1994 and in 1999. Subjects were classified as having FCH when total
      cholesterol and/or triglyceride levels exceeded the 90th percentile adjusted for
      age and sex. In 1994, 93 (31%) of the 299 subjects were affected, whereas 206
      (69%) of the subjects were unaffected relatives. In 1999, a diagnosis of FCH was
      consistent in 69 (74%) of the 93 subjects. So, 26% of the FCH subjects in 1994
      showed a sporadic normolipidemic pattern (ie, total cholesterol and/or
      triglycerides <90th percentile) in 1999. Among the 206 unaffected relatives in
      1994, 178 (86%) remained unaffected in 1999, and 28 (14%) developed an FCH lipid
      phenotype. Multiple regression analysis showed that sex (odds ratio 2.03, 95% CI
      1.09 to 3.87; P=0.03) and body mass index (odds ratio 1.14, 95% CI 1.05 to 1.24;
      P<0.01) significantly contributed to the variability in lipid phenotype
      expression. Thus, a diagnosis of FCH, based on plasma total cholesterol and/or
      triglyceride levels, is consistent in only 74% of the subjects over a 5-year
      period. Two other major characteristics of our FCH group, compared with the
      unaffected relatives, included elevated apolipoprotein B (apoB) levels and the
      presence of small dense low density lipoprotein (LDL), as reflected by a low
      value of the parameter K (apoB 1461 +/- 305 versus 997 +/- 249 mg/L, respectively
      [P < 0.001]; K value -0.22 +/- 0.19 versus -0.02 +/- 0.19, respectively [P <
      0.001]). We now report that the apoB concentration and the K value show less
      variability in time and are more consistently associated with FCH, inasmuch as
      affected FCH subjects, compared with the unaffected relatives, persistently show
      a higher apoB level and a lower value of parameter K, reflecting small dense LDL,
      even when they present a sporadic normolipidemic pattern. In conclusion, our
      results emphasize the need for reevaluation of the diagnostic criteria for FCH.
      We demonstrate that apoB and small dense LDL are attractive new candidates for
      defining FCH. Further studies are indicated to evaluate the role of apoB and
      small dense LDL as diagnostic criteria for FCH.

PMID- 11834529
TI  - Increased intima-media thickness in familial combined hyperlipidemia associated
      with apolipoprotein B.
AB  - The aim of the present study was to quantify intima-media thickness (IMT) in
      familial combined hyperlipidemia (FCHL) and to evaluate the relationship of IMT
      in FCHL-affected subjects with lipids and apolipoproteins, blood pressure values,
      and surrogate markers of insulin resistance. IMT was measured by ultrasound at
      the left and right common carotid arteries in 46 FCHL-affected subjects who were
      free of clinical manifestations of atherosclerosis and in 55 age- and sex-matched
      healthy control subjects. FCHL-affected subjects had significantly increased IMT
      compared with healthy control subjects, with a difference of 57 microm (age- and
      sex-corrected P<0.01). In the FCHL group, significantly positive age- and sex
      corrected univariate correlations were observed between IMT and total
      cholesterol, non-high density lipoprotein cholesterol, and apolipoprotein B.
      Multivariate regression analyses revealed that age, sex, and apolipoprotein B
      were significant and independent predictors of IMT, whereas body mass index was
      of borderline significance. Combined, these factors explained almost 50% of the
      observed IMT variation (P<0.001). The increased IMT observed in FCHL corresponds
      with approximately 7 years of physiological IMT increase in excess of the average
      IMT in age- and sex-matched control subjects. These novel findings show the
      important relationship between lipoprotein particles, marked by increased
      apolipoprotein B concentrations, and an increased IMT in FCHL. The increased IMT
      in FCHL-affected subjects is in agreement with the known high risk of
      cardiovascular disease in FCHL.

PMID- 11834530
TI  - Postprandial plasma ApoB-48 levels are influenced by a polymorphism in the
      promoter of the microsomal triglyceride transfer protein gene.
AB  - The microsomal triglyceride transfer protein (MTP) plays a key role in the
      secretion of apolipoprotein B (apoB)-containing lipoproteins. The rare variant of
      a functional polymorphism in the promoter region of the MTP gene has been
      associated with elevated transcriptional activity of the gene in vitro (MTP
      493G/T). With use of a "recruit-by-genotype" approach, we investigated one of the
      potentially complex phenotypes of this polymorphism, the appearance in plasma of
      apoB-48 after a meal intake. A total of 12 homozygous carriers of the rare MTP
      493T variant were identified from a population-based screening of 50-year-old
      healthy white men. All subjects were of the apoE3/3 genotype. Along with 48
      baseline well-matched heterozygotes (n=24) plus homozygotes (n=24) for the common
      variant, they were given a standardized oral fat meal. Postprandial plasma
      concentrations of apoB-48 were determined by the combination of density gradient
      ultracentrifugation and analytical SDS-PAGE. The postprandial plasma
      concentrations of triglycerides did not differ between the groups, but homozygous
      carriers of the rare MTP-493T variant showed a >100% greater increase in apoB-48
      in the smallest (Svedberg flotation rate constant 20 to 60) triglyceride-rich
      lipoprotein fraction (P=0.005). These data support the notion that elevated
      transcriptional activity of MTP leads to an increased generation of the smallest
      triglyceride-rich lipoprotein from the intestine.

PMID- 11834531
TI  - Expression of type III hyperlipoproteinemia in apolipoprotein E2 (Arg158 --> Cys)
      homozygotes is associated with hyperinsulinemia.
AB  - Type III hyperlipoproteinemia (HLP) is mainly found in homozygous carriers of
      apolipoprotein E2 (apoE2, Arg158-->Cys). Only a small percentage (< 5%) of these
      apoE2 homozygotes develops hyperlipidemia, indicating that additional
      environmental and genetic factors contribute to the expression of type III HLP.
      In the present study, first, the prevalence of type III HLP among apoE2
      homozygotes was estimated in a Dutch population sample of 8888 participants.
      Second, 68 normocholesterolemic and 162 hypercholesterolemic apoE2 homozygotes
      (type III HLP patients) were collected to investigate additional factors
      influencing type III HLP expression. In the Dutch population sample, apoE2
      homozygosity occurred with a frequency of 0.6% (57 of 8888 individuals). Among
      the 57 E2/2 subjects, 10 type III HLP patients were identified (prevalence 18%).
      Comparison of normocholesterolemic E2/2 subjects and type III HLP patients showed
      that the latter had a significantly increased body mass index (25.6 +/- 4.0
      versus 26.9 +/- 3.8 kg/m(2), respectively; P=0.03) and prevalence of
      hyperinsulinemia (26% versus 63%, respectively; P<0.001). Multiple linear
      regression analysis demonstrated that most of the variability in type III HLP
      expression can be explained by fasting insulin levels (partial correlation
      coefficient approximately 0.50, P<0.001). In contrast to men, apoE2 homozygous
      women aged > or = 50 years had significantly higher plasma lipid levels than
      their counterparts aged < 50 years. These data demonstrate that the expression of
      type III HLP in E2/2 subjects is elicited to a large extent by hyperinsulinemia.
      In addition, in female apoE2 homozygotes, the expression increases with age; this
      increase is most likely due to the loss of estrogen production.

PMID- 11834532
TI  - Cellular antioxidant effects of atorvastatin in vitro and in vivo.
AB  - 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) may exert
      direct effects on vascular cells and beneficially influence endothelial
      dysfunction. Because reactive oxygen species (ROS) may lead to vascular damage
      and dysfunction, we investigated the effect of atorvastatin on ROS production and
      the underlying mechanisms in vitro and in vivo. Cultured rat aortic vascular
      smooth muscle cells were incubated with 10 micromol/L atorvastatin. Angiotensin
      II-induced and epidermal growth factor-induced ROS production were significantly
      reduced by atorvastatin (dichlorofluorescein fluorescence laser microscopy).
      Atorvastatin downregulated mRNA expression of the NAD(P)H oxidase subunit nox1,
      whereas p22phox mRNA expression was not significantly altered (reverse
      transcription-polymerase chain reaction, Northern analysis). Membrane
      translocation of rac1 GTPase, which is required for the activation of NAD(P)H
      oxidase, was inhibited by atorvastatin (Western blot). mRNA expression of
      superoxide dismutase isoforms and glutathione peroxidase was not modified by
      atorvastatin, whereas catalase expression was upregulated at mRNA and protein
      levels, resulting in an increased enzymatic activity. Effects of atorvastatin on
      ROS production and nox1, rac1, and catalase expression were inhibited by L
      mevalonate but not by 25-hydroxycholesterol. In addition, spontaneously
      hypertensive rats were treated with atorvastatin for 30 days. ROS production in
      aortic segments was significantly reduced in statin-treated rats (lucigenin
      chemiluminescence). Treatment with atorvastatin reduced vascular mRNA expression
      of p22phox and nox1 and increased aortic catalase expression. mRNA expression of
      superoxide dismutases, glutathione peroxidase, and NAD(P)H oxidase subunits
      gp91phox, p40phox, p47phox, and p67phox remained unchanged. Translocation of rac1
      from the cytosol to the cell membrane was also reduced in vivo. Thus,
      atorvastatin exerts cellular antioxidant effects in cultured rat vascular smooth
      muscle cells and in the vasculature of spontaneously hypertensive rats mediated
      by decreased expression of essential NAD(P)H oxidase subunits and by upregulation
      of catalase expression. These effects of atorvastatin may contribute to the
      vasoprotective effects of statins.

PMID- 11834534
TI  - Alcohol-extracted, but not intact, dietary soy protein lowers lipoprotein(a)
      markedly.
AB  - We previously found that dietary soy protein produces higher lipoprotein(a)
      [Lp(a)] plasma concentrations than does casein. This study tested the hypothesis
      that soy protein contains Lp(a)-raising alcohol-removable components. Twelve
      normolipidemic women and men consumed, in a crossover design, liquid-formula
      diets containing casein, soy protein, or alcohol-extracted soy protein. Dietary
      periods of 32 days were separated by washout periods on self-selected diets.
      Fasting lipid and Lp(a) levels were measured throughout. Median Lp(a)
      concentration was >2-fold greater after 28 to 32 days on a soy protein diet than
      after an extracted soy protein diet (P<0.001). Lp(a) concentrations after casein
      and extracted soy protein diets were virtually identical. Women and men responded
      similarly. When the switch was made from a self-selected to a soy protein diet,
      median Lp(a) concentration increased 16% after 1 week (P<0.01) and subsequently
      decreased toward baseline; extracted soy protein and casein diets never exhibited
      increased median Lp(a) levels, and after 28 to 32 days, these levels were
      decreased >60% below baseline (P<0.001 and P<0.01, respectively). Low density
      lipoprotein cholesterol concentrations were not different after the 3
      experimental diets. The data indicate that (1) dietary soy protein can increase
      Lp(a) concentrations, (2) this effect is eliminated after alcohol extraction, and
      (3) high Lp(a) concentrations may be markedly reduced by diet.

PMID- 11834533
TI  - Atorvastatin preferentially reduces LDL-associated platelet-activating factor
      acetylhydrolase activity in dyslipidemias of type IIA and type IIB.
AB  - Human plasma platelet-activating factor acetylhydrolase (PAF-AH) is a
      phospholipase A(2) that is primarily associated with low density lipoprotein
      (LDL). PAF-AH activity has also been found in high density lipoprotein (HDL),
      although it has recently been indicated that there is no PAF-AH protein in HDL.
      Plasma paraoxonase 1 (PON1) is an HDL-associated esterase, which also exhibits
      PAF-AH-like activity. The effect of atorvastatin (20 mg per day for 4 months) on
      PAF-AH and PON1 activities in patients with dyslipidemia of type IIA (n=55) or
      type IIB (n=21) was studied. In both patient groups, atorvastatin significantly
      reduced plasma PAF-AH activity because of the decrease in LDL plasma levels and
      the preferential decrease in PAF-AH activity on dense LDL subfractions (LDL-4 and
      LDL-5). Drug therapy did not affect HDL-associated PAF-AH activity or serum PON1
      activities toward paraoxon and phenylacetate in either patient group. However,
      because of the reduction in LDL cholesterol levels, the ratios of HDL-associated
      PAF-AH and serum PON1 activities to LDL cholesterol levels were significantly
      increased after drug administration. The reduction of the LDL-associated PAF-AH
      activity and the elevation in the ratios of HDL-associated PAF-AH and PON1
      activities to LDL plasma levels may represent a new dimension in the
      antiatherogenic effect of atorvastatin.

PMID- 11834535
TI  - Increased carotid artery intima-media thickness in subjects with primary
      hypoalphalipoproteinemia.
AB  - The plasma concentration of high-density lipoprotein cholesterol (HDL-C) is
      inversely correlated with the incidence of atherosclerotic vascular events. In
      the present study, we evaluated pre-intrusive atherosclerosis in subjects with
      plasma HDL-C at the extremities of normal distribution. Fifty-five subjects with
      primary hypoalphalipoproteinemia (HypoALP) or hyperalphalipoproteinemia
      (HyperALP) were compared with fifty-five control subjects with average HDL-C
      levels, matched for sex, age, and plasma cholesterol. The average and maximal
      intima-media thicknesses (Avg-IMT and Max-IMT) of 48 carotid segments for each
      subject were approximately 40% greater in HypoALP than in control subjects (0.94
      +/- 0.06 versus 0.69 +/- 0.04 mm, P=0.004, and 1.86 +/- 0.16 versus 1.35 +/- 0.10
      mm, P=0.025, respectively). The IMT values in HyperALP subjects (Avg-IMT, 0.71 +/
      0.04 and Max-IMT, 1.38 +/- 0.14 mm) were the same as in controls. In a large
      cohort of hyperlipidemic subjects (n=559), significantly greater Avg-IMT and Max
      IMT were found in subjects belonging to the first HDL-C quintile (<42 mg/dL) than
      in all the others. The measurement of carotid IMT in cases with HypoALP and
      HyperALP, and in a large series of hyperlipidemic patients, thus indicates that a
      low HDL-C is associated with significant pre-intrusive atherosclerosis, whereas a
      HDL-C level above average values does not lead to a further reduction of arterial
      wall thickening.

PMID- 11834536
TI  - Inhibition of platelet glycoprotein Ib, glycoprotein IIb/IIIa, or both by
      monoclonal antibodies prevents arterial thrombosis in baboons.
AB  - The antithrombotic efficacy of the monoclonal antibodies 6B4-Fab and MA-16N7C2
      against platelet glycoprotein (GP) Ib and GP IIb/IIIa, respectively, on acute
      platelet-mediated thrombosis was evaluated in a baboon model of femoral artery
      stenosis, which is a modification of the original Folts model: platelet thrombi
      form on the injured stenosed artery, producing cyclic flow reductions (CFRs). A
      dose of 0.6 mg/kg 6B4-Fab significantly reduced the CFRs by 59 +/- 15%, whereas 2
      mg/kg 6B4-Fab completely abolished the CFRs without prolongation of the bleeding
      time. MA-16N7C2 inhibited CFRs by 43 +/- 8% at a dose of 0.1 mg/kg and abolished
      the CFRs at a dose of 0.3 mg/kg but with a significant prolongation of the
      bleeding time. Finally, the combination of 0.6 mg/kg 6B4-Fab and 0.1 mg/kg MA
      16N7C2 fully prevented the CFRs without prolongation of the bleeding time. The
      present study demonstrates that the inhibition of platelet GP Ib function by 6B4
      Fab is a powerful intervention to prevent platelet thrombus formation in injured
      arteries without prolongation of the bleeding time; the latter is in contrast to
      the result after the inhibition of GP IIb/IIIa. Moreover, we demonstrate that
      combining a GP Ib blocker with a GP IIb/IIIa blocker can achieve a strong
      antithrombotic effect without increasing the bleeding time. This provides new
      information that will be beneficial in designing clinical therapeutic approaches.

PMID- 11834537
TI  - Platelet shape changes and adhesion under high shear flow.
AB  - Recent studies have revealed that the platelet adhesive process under flow is
      tightly regulated by multiple ligand-receptor interactions. However, platelet
      morphological changes during this process, particularly its physiological
      relevance, remain unknown under blood flow conditions. Using epifluorescence and
      scanning electron microscopy, we evaluated the real-time changes in platelet
      morphology during a platelet adhesive process on a von Willebrand factor-coated
      surface under physiological high shear flow in a perfusion chamber. Here, we show
      that dynamic platelet shape changes occurring during distinct phases of the
      adhesive process are precisely regulated by "inside-out" and "outside-in"
      integrin signals and are also a key regulatory element in successful platelet
      thrombogenesis opposing rapid blood flow in vivo.

PMID- 11834538
TI  - Amount of H antigen expressed on circulating von Willebrand factor is modified by
      ABO blood group genotype and is a major determinant of plasma von Willebrand
      factor antigen levels.
AB  - To investigate whether the effect of ABO blood group on plasma von Willebrand
      factor (vWF) levels is mediated by the ABH antigenic determinants carried on N
      linked glycans of vWF, we studied 158 group A and group O healthy volunteers. vWF
      antigen (vWF:Ag) and factor VIII antigen (FVIII:Ag) levels were highest in
      A(1)A(1) individuals and higher in A(1)O(1) than in A(2)O(1) or O(1)O(1)
      individuals. Plasma A transferase activity and the amount of A antigen expressed
      per unit vWF (AvWF) were significantly higher in A(1)A(1) than in A(1)O(1)
      individuals and higher in A(1)O(1) than in A(2)O(1) individuals. AvWF was
      correlated strongly with plasma levels of A transferase activity. Thus, we have
      clearly demonstrated a direct relationship between ABO genotype, A transferase
      expression, and the amount of A antigen expressed on circulating vWF. H antigen
      expression per unit vWF (HvWF) was highest in group O individuals. Among group A
      individuals, the pattern of HvWF expression was A(2)O(1)>A(1)O(1)>A(1)A(1). In
      group O and group A(2)O(1) individuals, HvWF was inversely correlated with plasma
      vWF levels. In contrast, among group A(1)A(1) and A(1)O(1) individuals, there was
      no relationship between AvWF and plasma vWF levels. These findings suggest that
      it is H antigen expression that mediates the ABO effect on plasma vWF
      concentration.

PMID- 11834539
TI  - Influence of anatomical location on arterial thrombosis.
AB  - Atherosclerosis manifests as a systemic disease with near global involvement of
      the named segments of the arterial tree. Acute thrombotic arterial occlusion,
      however, is not equally distributed. To evaluate intra-individual regional
      differences in arterial thrombogenicity, we compared (111)In-platelet deposition
      in porcine carotid and femoral arteries after a standardized crush injury. Within
      the unidirectional flow conditions of elastic carotid arteries, platelet
      deposition was more than 3-fold higher compared with predominantly muscular
      femoral arteries with triphasic arterial flow. To determine the influence of
      rheology on platelet deposition after crush injury, carotid arteries were
      transplanted into the femoral position and compared with the paired native
      carotid and femoral arteries. Similarly, femoral arteries transposed to the
      carotid position were compared with the paired native carotid artery. In each of
      these experiments, arterial transposition to a new anatomic location imparts a
      predilection for platelet deposition indigenous to the new location. In the
      controlled environment of two high-shear thrombin-independent and -dependent flow
      chambers, porcine carotid and femoral arterial substrates were indistinguishable
      from one another with respect to platelet deposition. Regional differences in
      arterial hemodynamics may account for substantial differences in thrombosis
      arising from deep arterial injury.

PMID- 11834540
TI  - Factor XIIIA Val34Leu polymorphism does not predict risk of coronary heart
      disease: The Atherosclerosis Risk in Communities (ARIC) Study.
AB  - Factor XIII catalyzes the cross-linking of fibrin. Cross-sectional studies have
      suggested that a common polymorphism site at residue 34 of the A subunit of
      factor XIII (FXIIIA) with a substitution of Leu for Val (FXIIIA Val34Leu) was
      associated with reduced coronary heart disease (CHD). This association has not
      been examined in prospective studies. Healthy subjects (n=15 792) were recruited
      from 4 US communities into the Atherosclerosis Risk in Communities (ARIC) study
      from 1987 to 1989. They were followed, and incident CHD events were identified
      and verified. For the present study, we included 423 patients with CHD as cases
      and 479 noncases. FXIIIA Val34Leu polymorphism was determined by the single
      strand conformational polymorphism method. There were no significant differences
      in the genotype frequencies between cases and noncases. The genotypes showed
      little association with known CHD risk factors. A weighted proportional hazards
      regression analysis adjusting for other risk factors confirmed no association of
      the genotypes with risk of CHD. This prospective study did not provide evidence
      of a reduced CHD risk for the FXIIIA 34Leu allele.

PMID- 11834541
TI  - Hemostatic factors as predictors of coronary events and total mortality: The
      FINRISK '92 Hemostasis Study.
AB  - The role of hemostatic factors as predictors of coronary heart disease (CHD) and
      total mortality is poorly understood. Therefore, we carried out a prospective
      cohort study in Finland. In 1992, a random population sample of 2378 men and
      women aged 45 to 64 years was investigated and then followed up until December
      31, 1998. During the follow-up, 133 CHD events were observed; 73 were among
      participants free of CHD at baseline. The total number of deaths was 124. After
      adjustment for traditional risk factors and prevalent CHD at baseline and
      correction for regression dilution bias, a 1-SD increase in plasminogen was
      associated with a 1.41-fold (95% CI 1.09 to 1.81) increase in CHD risk. The
      predictive power of plasminogen depended significantly on the level of total
      cholesterol being stronger for persons with high cholesterol. A 1-SD increase in
      fibrinogen was associated with a 1.23-fold (95% CI 1.05 to 1.44) increase in all
      cause mortality, but its association with CHD events did not reach statistical
      significance. Factor VII antigen or coagulant activity or lipoprotein(a) were not
      independent predictors of CHD risk. These findings support the role of
      plasminogen as a risk factor for CHD events.

PMID- 11834542
TI  - Medicine in the age of global interdependence.

PMID- 11834543
TI  - Complex political emergencies.

PMID- 11834545
TI  - Quality of economic evaluations in health care.

PMID- 11834544
TI  - Treating rheumatoid arthritis with tumour necrosis factor alpha blockade.

PMID- 11834547
TI  - Conditions at Afghan prison violate human rights, report says.

PMID- 11834548
TI  - New research on autism and measles "proves nothing".

PMID- 11834550
TI  - NHS to fund treatment for 10000 patients with MS.

PMID- 11834551
TI  - Human rights group uncovers evidence of torture in Zimbabwe.

PMID- 11834552
TI  - Afghanistan needs security to rebuild its health services.

PMID- 11834554
TI  - Separating humanitarian aid from politics.

PMID- 11834553
TI  - Getting the doctors to return.

PMID- 11834556
TI  - Congo health officials draw up measures for war conditions.

PMID- 11834555
TI  - Palestinian territories face huge burden of disability.

PMID- 11834557
TI  - Post-combat syndromes from the Boer war to the Gulf war: a cluster analysis of
      their nature and attribution.
AB  - OBJECTIVES: To discover whether post-combat syndromes have existed after modern
      wars and what relation they bear to each other. DESIGN: Review of medical and
      military records of servicemen and cluster analysis of symptoms. DATA SOURCES:
      Records for 1856 veterans randomly selected from war pension files awarded from
      1872 and from the Medical Assessment Programme for Gulf war veterans. MAIN
      OUTCOME MEASURES: Characteristic patterns of symptom clusters and their relation
      to dependent variables including war, diagnosis, predisposing physical illness,
      and exposure to combat; and servicemen's changing attributions for post-combat
      disorders. RESULTS: Three varieties of post-combat disorder were identified-a
      debility syndrome (associated with the 19th and early 20th centuries), somatic
      syndrome (related primarily to the first world war), and a neuropsychiatric
      syndrome (associated with the second world war and the Gulf conflict). The era in
      which the war occurred was overwhelmingly the best predictor of cluster
      membership. CONCLUSIONS: All modern wars have been associated with a syndrome
      characterised by unexplained medical symptoms. The form that these assume, the
      terms used to describe them, and the explanations offered by servicemen and
      doctors seem to be influenced by advances in medical science, changes in the
      nature of warfare, and underlying cultural forces.

PMID- 11834558
TI  - Discrepancies in autobiographical memories--implications for the assessment of
      asylum seekers: repeated interviews study.
AB  - OBJECTIVE: To investigate the consistency of autobiographical memory of people
      seeking asylum, in light of the assumption that discrepancies in asylum seekers'
      accounts of persecution mean that they are fabricating their stories. DESIGN:
      Repeated interviews. SETTING: England, 1999 and 2000. PARTICIPANTS: Community
      sample of 27 Kosovan and 12 Bosnian refugees. MAIN OUTCOME MEASURES:
      Discrepancies in repeated descriptions of one traumatic and one non-traumatic
      event, including specific details, rated as central or peripheral to the event.
      Self report measures of post-traumatic stress disorder and depression. RESULTS:
      Discrepancies between an individual's accounts were common. For participants with
      high levels of post-traumatic stress, the number of discrepancies increased with
      length of time between interviews. More discrepancies occurred in details
      peripheral to the account than in details that were central to the account.
      CONCLUSION: The assumption that inconsistency of recall means that accounts have
      poor credibility is questionable. Discrepancies are likely to occur in repeated
      interviews. For refugees showing symptoms of high levels of post-traumatic
      stress, the length of the application process may also affect the number of
      discrepancies. Recall of details rated by the interviewee as peripheral to the
      account is more likely to be inconsistent than recall of details that are central
      to the account. Thus, such inconsistencies should not be relied on as indicating
      a lack of credibility.

PMID- 11834559
TI  - Influenza vaccination rates and informed consent in Dutch nursing homes: survey
      of nursing home physicians.

PMID- 11834560
TI  - Systematic review of randomised controlled trials of over the counter cough
      medicines for acute cough in adults.
AB  - OBJECTIVES: To determine whether over the counter cough medicines are effective
      for acute cough in adults. DESIGN: Systematic review of randomised controlled
      trials. DATA SOURCES: Search of the Cochrane Acute Respiratory Infections Group
      specialised register, Cochrane Controlled Trials Register, Medline, Embase, and
      the UK Department of Health National Research Register in all languages. INCLUDED
      STUDIES: All randomised controlled trials that compared oral over the counter
      cough preparations with placebo in adults with acute cough due to upper
      respiratory tract infection in ambulatory settings and that had cough symptoms as
      an outcome. RESULTS: 15 trials involving 2166 participants met all the inclusion
      criteria. Antihistamines seemed to be no better than placebo. There was
      conflicting evidence on the effectiveness of antitussives, expectorants,
      antihistamine-decongestant combinations, and other drug combinations compared
      with placebo. CONCLUSION: Over the counter cough medicines for acute cough cannot
      be recommended because there is no good evidence for their effectiveness. Even
      when trials had significant results, the effect sizes were small and of doubtful
      clinical relevance. Because of the small number of trials in each category, the
      results have to be interpreted cautiously.

PMID- 11834561
TI  - Chemical weapons.

PMID- 11834562
TI  - Biological warfare and bioterrorism.

PMID- 11834563
TI  - Lesson of the week: Post-traumatic stress disorder following military combat or
      peace keeping.

PMID- 11834564
TI  - Root causes of violent conflict in developing countries.

PMID- 11834565
TI  - Armed conflict as a public health problem.

PMID- 11834567
TI  - Was the Afghan conflict a just war?

PMID- 11834566
TI  - Children of war: the real casualties of the Afghan conflict.

PMID- 11834569
TI  - Nuclear terrorism.

PMID- 11834570
TI  - Letter from Afghanistan.

PMID- 11834571
TI  - Israeli-Palestinian conflict. Need for medical services for Palestinians injured
      in West Bank is urgent.

PMID- 11834572
TI  - Conflict in Sri Lanka. Sri Lanka's health service is a casualty of 20 years of
      war.

PMID- 11834573
TI  - To combat terrorism, United Nations must be in charge.

PMID- 11834575
TI  - Good governance must be introduced globally.

PMID- 11834576
TI  - "Functional" should not be shorthand for "I don't know" in dyspepsia.

PMID- 11834577
TI  - Double standards seem to prevail for generic drugs.

PMID- 11834578
TI  - Patient safety is more important than efficiency.

PMID- 11834579
TI  - Parents are the best judges of school attendance.

PMID- 11834580
TI  - Use of digitalisize and digitalize.

PMID- 11834587
TI  - Obtaining olfactory ensheathing cells from extra-cranial sources a step closer to
      clinical transplant-mediated repair of the CNS?

PMID- 11834588
TI  - Brain function in Duchenne muscular dystrophy.
AB  - Duchenne muscular dystrophy (DMD) is the second most commonly occurring
      genetically inherited disease in humans. It is an X-linked condition that affects
      approximately one in 3300 live male births. It is caused by the absence or
      disruption of the protein dystrophin, which is found in a variety of tissues,
      most notably skeletal muscle and neurones in particular regions of the CNS.
      Clinically DMD is characterized by a severe pathology of the skeletal musculature
      that results in the premature death of the individual. An important aspect of DMD
      that has received less attention is the role played by the absence or disruption
      of dystrophin on CNS function. In this review we concentrate on insights into
      this role gained from investigation of boys with DMD and the genetically most
      relevant animal model of DMD, the dystrophin-deficient mdx mouse. Behavioural
      studies have shown that DMD boys have a cognitive impairment and a lower IQ
      (average 85), whilst the mdx mice display an impairment in passive avoidance
      reflex and in short-term memory. In DMD boys, there is evidence of disordered CNS
      architecture, abnormalities in dendrites and loss of neurones, all associated
      with neurones that normally express dystrophin. In the mdx mouse, there have been
      reports of a 50% decrease in neurone number and neural shrinkage in regions of
      the cerebral cortex and brainstem. Histological evidence shows that the density
      of GABA(A) channel clusters is reduced in mdx Purkinje cells and hippocampal CA1
      neurones. At the biochemical level, in DMD boys the bioenergetics of the CNS is
      abnormal and there is an increase in the levels of choline-containing compounds,
      indicative of CNS pathology. The mdx mice also display abnormal bioenergetics,
      with an increased level of inorganic phosphate and increased levels of choline
      containing compounds. Functionally, DMD boys have EEG abnormalities and there is
      some preliminary evidence that synaptic function is affected adversely by the
      absence of dystrophin. Electrophysiological studies of mdx mice have shown that
      hippocampal neurones have an increased susceptibility to hypoxia. These recent
      findings on the role of dystrophin in the CNS have implications for the clinical
      management of boys with DMD.

PMID- 11834589
TI  - Olfactory ensheathing cells promote locomotor recovery after delayed
      transplantation into transected spinal cord.
AB  - We demonstrated recently that transplantation of olfactory ensheathing cells from
      the nasal olfactory mucosa can promote axonal regeneration after complete
      transection of the spinal cord in adult rat. Ten weeks after transection and
      transplantation there was significant recovery of locomotor behaviour and
      restoration of descending inhibition of spinal cord reflexes, accompanied by
      growth of axons across the transection site, including serotonergic axons arising
      from the brainstem raphe nuclei. The present experiment was undertaken to
      determine whether olfactory ensheathing cells from the olfactory mucosa are
      capable of promoting regeneration when transplanted into the spinal cord 4 weeks
      after transection. Under general anaesthesia, thoracic spinal cord at the T10
      level was transected completely in adult rats. Four weeks later, the scar tissue
      and cavities at the transection site were removed to create a 3-4 mm gap. Into
      this gap, between the cut surfaces of the spinal cord, pieces of olfactory lamina
      propria were placed. Ten weeks later, the locomotor activity of these animals was
      significantly improved compared with control animals, which received implants of
      either pieces of nasal respiratory lamina propria or collagen (Basso, Beattie,
      Bresnahan Locomotor Rating Scale scores 4.3 + 0.8, n = 6 versus 1.0 + 0.2, n =
      10, respectively; P < 0.001). Ten weeks after transplantation the behavioural
      recovery was still improving. Regrowth of brainstem raphe axons across the
      transplant site was shown by the presence of serotonergic axons in the spinal
      cord caudal to the transection site, and by retrograde labelling of cells in the
      nucleus raphe magnus after injections of fluorogold into the caudal spinal cord.
      Neither serotonergic axons nor labelled brainstem cells were observed in the
      control animals. These results indicate that olfactory ensheathing cells from the
      nasal olfactory lamina propria have the ability to promote spinal cord
      regeneration when transplanted 4 weeks after complete transection. Olfactory
      ensheathing cells are accessible and available in the human nose; the present
      study further supports clinical use of these cells in repairing the human spinal
      cord via autologous transplantation.

PMID- 11834590
TI  - Drug resistance in epilepsy: expression of drug resistance proteins in common
      causes of refractory epilepsy.
AB  - Epilepsy is resistant to drug treatment in about one-third of cases, but the
      mechanisms underlying this drug resistance are not understood. In cancer, drug
      resistance has been studied extensively. Amongst the various resistance
      mechanisms, overexpression of drug resistance proteins, such as multi-drug
      resistance gene-1 P-glycoprotein (MDR1) and multidrug resistance-associated
      protein 1 (MRP1), has been shown to correlate with cellular resistance to
      anticancer drugs. Previous studies in human epilepsy have shown that MDR1 and
      MRP1 may also be overexpressed in brain tissue from patients with refractory
      epilepsy; expression has been shown in glia and neurones, which do not normally
      express these proteins. We examined expression of MDR1 and MRP1 in refractory
      epilepsy from three common causes, dysembryoplastic neuroepithelial tumours
      (DNTs; eight cases), focal cortical dysplasia (FCD; 14 cases) and hippocampal
      sclerosis (HS; eight cases). Expression was studied immunohistochemically in
      lesional tissue from therapeutic resections and compared with expression in
      histologically normal adjacent tissue. With the most sensitive antibodies, in all
      eight DNT cases, reactive astrocytes within tumour nodules expressed MDR1 and
      MRP1. In five of eight HS cases, reactive astrocytes within the gliotic
      hippocampus expressed MDR1 and MRP1. Of 14 cases of FCD, MDR1 and MRP1 expression
      was noted in reactive astrocytes in all cases. In five FCD cases, MRP1 expression
      was also noted in dysplastic neurones. In FCD and DNTs, accentuation of
      reactivity was noted around lesional vessels. Immunoreactivity was always more
      frequent and intense in lesional reactive astrocytes than in glial fibrillary
      acidic protein-positive reactive astrocytes in adjacent histologically normal
      tissue. MDR1 is able to transport some antiepileptic drugs (AEDs), and MRP1 may
      also do so. The overexpression of these drug resistance proteins in tissue from
      patients with refractory epilepsy suggests one possible mechanism for drug
      resistance in patients with these pathologies. We propose that overexpressed
      resistance proteins lower the interstitial concentration of AEDs in the vicinity
      of the epileptogenic pathology and thereby render the epilepsy caused by these
      pathologies resistant to treatment with AEDs.

PMID- 11834591
TI  - Distribution of glutamate transporters in the hippocampus of patients with
      pharmaco-resistant temporal lobe epilepsy.
AB  - In patients suffering from temporal lobe epilepsy (TLE), increased extracellular
      glutamate levels in the epileptogenic hippocampus both during and after clinical
      seizures have been reported. These increased glutamate levels could be the result
      of malfunctioning and/or downregulation of glutamate transporters (also known as
      EAATs; excitatory amino acid transporters). In this study, the distribution of
      protein and mRNA of EAAT subtypes was examined in the hippocampus of TLE patients
      with hippocampal sclerosis (HS group) and without hippocampal sclerosis (non-HS
      group), and in autopsy controls without neurological disorders. EAAT protein
      localization was studied by immunohistochemistry on paraffin sections using
      specific poly- and monoclonal antibodies against the glial glutamate transporters
      EAAT1 and EAAT2 and the neuronal glutamate transporter EAAT3. Antibody
      specificity was shown by immunoblotting. In the HS group, a small decrease in
      EAAT1-immunoreactivity (IR) was observed in CA4 and in the polymorphic and
      supragranular layer of the dentate gyrus, compared with the control group. The
      strongest changes were found for EAAT2 levels. In the non-HS group, increased
      EAAT2-IR was detected in the CA1 and CA2 field, compared with non-epileptic
      controls. EAAT2-IR was decreased in the HS compared with the non-HS group. Fewer
      EAAT3-positive cells were found in the HS group than in the non-HS and control
      group. In both TLE groups, increased EAAT3 levels were observed in individual
      neurones. In the HS group, the percentage of EAAT3-IR neurones was increased in
      CA2 and in the granule cell layer of the dentate gyrus. Radioactive in situ
      hybridization for EAAT1-3 confirmed our immunohistochemical results. Non
      radioactive in situ hybridization showed that not only astrocytes, but also
      neurones express EAAT2 mRNA. Taken together, differences in both mRNA and protein
      levels of glutamate transporter subtypes were found in specific regions in the
      TLE hippocampus, with most severe changes found for EAAT2 and EAAT3 levels. The
      results indicate an upregulation of EAAT2 protein expression in CA1 and CA2 in
      neurones in the non-HS group. This is in line with decreased EAAT2 protein levels
      in the HS group, since these hippocampi are characterized by severe neuronal cell
      loss. The functional consequences (glutamate transport capacity) of the reported
      changes in EAAT2 and EAAT3 remain to be determined.

PMID- 11834592
TI  - Two large British kindreds with familial Parkinson's disease: a clinico
      pathological and genetic study.
AB  - We present the findings of a study of two large unrelated kindreds with autosomal
      dominant Parkinson's disease. The affected members were assessed clinically and
      with [(18)F]6-fluorodopa-PET and were indistinguishable from patients with the
      sporadic form of Parkinson's disease. In one kindred, an affected member was
      examined subsequently at autopsy and Lewy bodies were present in a distribution
      typical of sporadic Parkinson's disease. These kindreds are distinct from other
      Parkinsonian kindreds with identified genetic loci (PARK1-4) and provide further
      evidence for genetic heterogeneity in familial Parkinson's disease.

PMID- 11834593
TI  - Seeing, since childhood, without ventral stream: a behavioural study.
AB  - We report the case of a 30-year-old man (S.B.) who developed visual agnosia
      following a meningoencephalitis at the age of 3 years. MRI disclosed extensive
      bilateral lesions of the occipital temporal visual pathway (ventral stream) and
      lesions in the right dorsal pathway, sparing primary visual cortices. S.B. showed
      a severe visual recognition deficit (texture, colour, objects, faces and words),
      although movement and space perception were largely preserved. His remaining
      visual capacities illustrate the competence of an isolated dorsal system which
      essentially functions on the sole basis of magnocellular afferents (low spatial
      resolution, high sensitivity to low contrast and moving stimuli). Patient S.B.
      also shows remarkable visuomotor competences, despite his perceptual limitations.
      It is suggested that his perceptual capacities correspond to the visual
      processing limitations of the dorsal visual stream, which in this patient have
      become accessible to perceptual awareness.

PMID- 11834594
TI  - BDNF and gp145trkB in multiple sclerosis brain lesions: neuroprotective
      interactions between immune and neuronal cells?
AB  - Recent immunohistological and imaging studies emphasize the crucial role of
      axonal injury in determining the extent of permanent neurological deficits in
      patients with multiple sclerosis. We have recently shown that human immune cells
      are capable of producing the neurotrophin brain-derived neurotrophic factor
      (BDNF), which can prevent axonal and neuronal damage after various pathological
      insults. BDNF imported into the CNS by immune cells would thus be an attractive
      candidate for mediating neuroprotective effects in multiple sclerosis. The aim of
      the present study was to perform a detailed immunohistochemical analysis of the
      expression of BDNF and its receptor truncated trkB tyrosine kinase receptor
      (gp145trkB) in a series of multiple sclerosis brain lesions. Our data show that
      various types of neurones throughout the brain are BDNF immunopositive in
      multiple sclerosis patients as well as in controls. Furthermore, in multiple
      sclerosis lesions, BDNF is primarily present in immune cells (T cells,
      macrophages/microglia) and reactive astrocytes. The number of BDNF immunopositive
      cells correlates with lesional demyelinating activity. The BDNF receptor
      gp145trkB is found in neurones in the immediate vicinity of multiple sclerosis
      plaques as well as in reactive astrocytes within the lesion, but not in immune
      cells. Our results demonstrate that both BDNF and gp145trkB are expressed in
      multiple sclerosis lesions. This suggests that BDNF and gp145trkB are involved in
      immune-mediated neuroprotective interactions in multiple sclerosis, and supports
      the concept that immune cells produce both damaging and protective factors in
      multiple sclerosis lesions.

PMID- 11834595
TI  - Olfactory learning: convergent findings from lesion and brain imaging studies in
      humans.
AB  - The role of temporal lobe structures in olfactory memory was investigated by (i)
      the examination of odour learning and memory in patients who had undergone
      resection from a temporal lobe (including primary olfactory regions) for the
      treatment of intractable epilepsy; and (ii) the examination of brain function
      during odour memory tasks as assessed via PET imaging of healthy individuals. In
      order to study different stages of odour memory, recognition of a 'list' of
      odours was tested after a first exposure, again after four exposures and once
      more after a 24 h delay interval. Patients with resection from a temporal lobe
      performed significantly less well than control subjects on all trials, and no
      significant differences were noted as a function of side of resection, indicating
      that there is not a strong hemispheric superiority for this task. The PET data
      yielded different levels of activity in piriform cortex (primary olfactory
      cortex), in relation to the 'no-odour' baseline scan, depending on the type of
      processing: no increase in activity noted during odour encoding, a small increase
      bilaterally during short-term recognition and a larger increase bilaterally
      during long-term recognition. These findings, together with findings in animal
      studies, suggest that piriform cortex may have an active role in odour memory
      processing, not simply in odour perception. Taken together, the findings from the
      lesion study and functional brain imaging of healthy subjects suggest that
      olfactory memory requires input from left and right temporal lobe regions for
      optimal odour recognition, and that, unlike with verbal or non-verbal visual
      material, there is not a strong functional lateralization for olfactory memory.

PMID- 11834597
TI  - Restoration of sensory function and lack of long-term chronic pain syndromes
      after brachial plexus injury in human neonates.
AB  - Obstetric complications are a common cause of brachial plexus injuries in
      neonates. Failure to restore sensation leads to trophic injuries and poor limb
      function. It is not known whether the infant suffers chronic neuropathic or
      spinal cord root avulsion pain; in adults, chronic pain is usual after spinal
      root avulsion injuries, and this is often intractable. The plexus is repaired
      surgically in severe neonatal injures; if no spontaneous recovery has occurred by
      3 months, and if neurophysiological investigations point to poor prognosis, then
      nerve trunk injures are grafted, while spinal cord root avulsion injuries are
      treated by transferring an intact neighbouring nerve (e.g. intercostal) to the
      distal stump of the damaged nerve, in an attempt to restore sensorimotor
      function. Using a range of non-invasive quantitative measures validated in
      adults, including mechanical, thermal and vibration perception thresholds, we
      have assessed for the first time sensory and cholinergic sympathetic function in
      24 patients aged between 3 and 23 years, who had suffered severe brachial plexus
      injury at birth. While recovery of function after spinal root avulsion was
      related demonstrably to surgery, there were remarkable differences from adults,
      including excellent restoration of sensory function (to normal limits in all
      dermatomes for at least one modality in 16 out of 20 operated cases), and
      evidence of exquisite CNS plasticity, i.e. perfect localization of restored
      sensation in avulsed spinal root dermatomes, now presumably routed via nerves
      that had been transferred from a distant spinal region. Sensory recovery exceeded
      motor or cholinergic sympathetic recovery. There was no evidence of chronic pain
      behaviour or neuropathic syndromes, although pain was reported normally to
      external stimuli in unaffected regions. We propose that differences in neonates
      are related to later maturation of injured fibres, and that CNS plasticity may
      account for their lack of long-term chronic pain after spinal root avulsion
      injury.

PMID- 11834596
TI  - Endothelin-1 potently induces Leao's cortical spreading depression in vivo in the
      rat: a model for an endothelial trigger of migrainous aura?
AB  - According to the 'neuronal' theory, cortical spreading depression (CSD) is the
      pathophysiological correlate of migrainous aura. However, the 'vascular' theory
      has implicated altered vascular function in the induction of aura symptoms. The
      possibility of a vascular origin of aura symptoms is supported, e.g. by the
      clinical observation that cerebral angiography frequently provokes migrainous
      aura. This suggests that endothelial irritation may somehow initiate one of the
      pathways resulting in migrainous aura. Up to now, an endothelium-derived factor
      has never been shown to trigger CSD. Here, for the first time, we demonstrate and
      characterize the ability of the vasoconstrictor and astroglial/neuronal modulator
      endothelin-1 to trigger Leao's 'spreading depression of activity' in vivo in
      rats. At a concentration range between 10 nM and 1 microM, endothelin-1 induced
      changes characteristic of CSD with regard to the rate of propagation, steady
      (direct current) potential and extracellular K(+)-concentration. A spreading
      hyperaemia followed by oligaemia was observed similar to those in K(+)-induced
      CSD. Endothelin-1 did not provoke changes characteristic of a terminal
      depolarization. The mechanism by which endothelin-1 generated CSD involved the N
      methyl-D-asparate receptor. Cerebral blood flow decreased slightly, but
      significantly, before endothelin-1 generated CSD. A vasodilator (NO*-donor)
      shifted the threshold for CSD induction to higher concentrations of endothelin-1.
      Endothelin-1, in contrast to K(+), did not induce CSD in rat brain slices
      suggesting indirectly that endothelin-1 may require intact perfusion to exert its
      effects. In conclusion, endothelin-1 was found in the experiment to be the most
      potent inducer of CSD currently known. We propose endothelin-1 as a possible
      candidate for the yet enigmatic link between endothelial irritation and
      migrainous aura.

PMID- 11834598
TI  - The effect of spatial and temporal information on saccades and neural activity in
      oculomotor structures.
AB  - It has been argued that saccade generation is supported by two systems, a'where'
      system that decides the direction and extent of an impending saccade, and a
      'when' system that is involved in the timing of the release of fixation. We
      evaluated the contributions of these systems to saccade latencies, and used
      functional MRI to identify the neural substrates of these systems. We found that
      advance knowledge of the direction and the timing of an impending target movement
      had both overlapping and discrete effects on saccade latencies and on neural
      activation. Knowledge of either factor decreased regular saccade latencies.
      However, knowledge of target direction increased the number of predictive and
      express saccades while knowledge of target timing did not. The brain activation
      data showed that advance knowledge of the direction or the timing of the target
      movement activated primarily overlapping structures. The precentral gyrus, in the
      region of the frontal eye fields, was more active in conditions in which some
      aspect of the target movement was predictable than in saccade control and
      fixation conditions. In the basal ganglia, activation discriminated between
      advance knowledge of target timing and target direction. The lenticular nuclei
      were more active when only target timing was known in advance, while the caudate
      was more active when only target direction was known in advance. These data
      suggest that the neural structures supporting the 'where' and 'when' systems are
      highly overlapping, although there is some dissociation sub-cortically. Knowledge
      of target timing and target direction converge in precentral gyrus, a region
      where there is strong evidence of context-dependent modulation of neural
      activity.

PMID- 11834599
TI  - Amygdala pathology in psychosis of epilepsy: A magnetic resonance imaging study
      in patients with temporal lobe epilepsy.
AB  - Psychosis of epilepsy (POE) has been recognized as a severe complication of
      chronic intractable epilepsy for more than a century. Most of the clinical
      symptoms of POE are reminiscent of schizophrenia. Nevertheless, there is general
      agreement that the phenomenology of POE differs from classical schizophrenia. The
      temporal lobe hypothesis of schizophrenia put forward in the 1960s notes that
      episodes with paranoid psychoses are more prevalent in temporal lobe epilepsy
      (TLE). However, the aetiology and pathogenesis of POE are poorly understood. One
      of the strongest biological findings in schizophrenia is volume loss of temporal
      lobe structures and the hippocampus in particular. In order to test the
      hypothesis that atrophy of the hippocampus and the amygdala is found in patients
      with TLE and POE, we performed a retrospective study of all patients with TLE who
      were admitted to the assessment unit of the Chalfont Centre for Epilepsy from
      1995 until 1999. Twenty-six (2.6%) of these 1008 patients fulfilled inclusion
      criteria and were compared with 24 patients with TLE without psychopathology and
      20 healthy volunteers. All patients underwent extensive MRI investigations,
      including volumetric data sets and quantitative T(2 )relaxometry. We found that
      patients with TLE and POE differed from patients with TLE alone and healthy
      volunteers in that the total brain volumes were significantly smaller. While
      there were no differences in hippocampal volumes between the three study groups,
      there was a significant 16-18% enlargement of the amygdala on both sides in
      patients with POE. Our findings support the notion that POE is a distinct
      nosologic entity differing from schizophrenia not only in clinical details but
      also in neurobiological aspects. The finding of amygdala enlargement agrees with
      the observation of an association between dysphoric disorders of epilepsy and POE
      described nearly 100 years ago.

PMID- 11834600
TI  - Genetic basis for clinical expression in multiple sclerosis.
AB  - Multiple sclerosis is a clinically heterogeneous demyelinating disease and an
      important cause of acquired neurological disability. An underlying complex
      genetic susceptibility plays an important role in multiple sclerosis aetiology;
      however, the role of genetic factors in determining clinical features of multiple
      sclerosis is unknown. We studied 184 stringently ascertained Caucasian multiple
      sclerosis families with multiple affected cases. A detailed evaluation of patient
      histories identified clinical variables including age of onset, initial clinical
      manifestations and disease severity. The concordance within families for
      continuous and categorical clinical variables was investigated using an
      intraclass correlation or Cohen's kappa coefficient, respectively. Genetic
      analyses included model-dependent, model-independent and association methodology.
      Linear and logistic regression models were used to evaluate the effect of human
      leucocyte antigen (HLA)-DR2 (DRB1*1501, DQB1*0602) on clinical outcome, taking
      account of correlation within families. Significant concordance for early
      clinical manifestations within families was observed for individuals with
      exclusive optic neuritis and/or spinal cord involvement as first and second
      multiple sclerosis attacks (P < 10(-6)). Linkage (LOD = 3.80, theta = 0.20) and
      association (P = 0.0002) to HLA-DR were present in the dataset; however, linkage
      was restricted to families in which the DR2 haplotype was present in at least one
      nuclear member. No evidence for linkage to HLA-DR in DR2-negative families was
      observed. When families were stratified by concordance of early clinical
      manifestations, a significant DR2 association was present in all subgroups.
      Concordance for early manifestations of multiple sclerosis was present in this
      familial dataset, but was not associated with HLA-DR2. The association of DR2 in
      families with different clinical presentations suggests that a common basis
      exists for susceptibility in multiple sclerosis. However, non-HLA genes or other
      epigenetic factors must modulate disease expression. Locus heterogeneity at the
      HLA region suggests a distinct immunopathogenesis in DR2 negative patients.

PMID- 11834601
TI  - Epstein-Barr virus myeloradiculitis and encephalomyeloradiculitis.
AB  - We provide a comprehensive clinical, radiological and virological analysis of
      four patients with Epstein-Barr virus (EBV) infection of the nervous system. One
      patient developed acute myeloradiculitis, one had acute
      encephalomyeloradiculitis, one had acute meningoencephalomyeloradiculitis and one
      had a subacute meningomyeloradiculitis. The ability of EBV to affect multiple
      parts of the entire neuraxis from meninges and brain to the spinal cord and
      peripheral nerves was evidenced by combinations of stiff neck and mental status
      changes, as well as patterns of weakness and sensory loss due to transverse
      myelitis or peripheral nerve disease. The CSF of all four patients contained a
      pleocytosis, predominantly mononuclear with elevated levels of protein, but a
      normal glucose level. In the two patients with acute myeloradiculitis and
      subacute meningomyeloradiculitis, the MRI revealed an increased signal in the
      spinal cord and lumbosacral roots, but in the two patients with acute
      encephalomyeloradiculitis and acute meningoencephalomyeloradiculitis, the brain
      and spinal cord MRIs were normal. In all four patients, EBV DNA, but not
      cytomegalovirus (CMV), herpes simplex virus (HSV) or varicella-zoster virus (VZV)
      DNA, was found in the CSF. The antibody pattern in serum was consistent with
      recent infection, and both EBV immunoglobulin (Ig) M and IgG antibodies, but not
      antibodies to HSV, VZV or CMV, were found in the CSF. Finally, there were reduced
      serum/CSF ratios of antibody to EBV, but not to total IgG or albumin, consistent
      with intrathecal antibody synthesis. None of the four patients died and none had
      brain swelling or focal changes according to brain MRI. Residual neurological
      deficits were evident. The two patients with acute myeloradiculitis and acute
      meningomyeloradiculitis had residual lower extremity weakness, and one of these
      patients later developed optic neuritis. The patient with acute
      encephalomyeloradiculitis had a moderate flaccid paraparesis, and the patient
      with subacute meningomyeloradiculitis was left with sensory loss in the feet.
      Compared with neurological disease caused by other herpes viruses, the clinical
      features of acute EBV myeloradiculitis, encephalomyeloradiculitis,
      encephalomyeloradiculitis and subacute meningomyeloradiculitis are distinctive.
      Of the eight human herpesviruses, EBV and VZV produce the most protean
      neurological syndromes. The mechanism by which EBV produces neurological disease
      is unknown. More correlative pathological, virological and immunological studies
      are needed in EBV-associated neurological disease.

PMID- 11834602
TI  - Paraneoplastic peripheral neuropathy associated with anti-Hu antibodies. A
      clinical and electrophysiological study of 20 patients.
AB  - Although paraneoplastic subacute sensory neuronopathy is the most frequent
      presentation of peripheral neuropathy in patients with anti-Hu antibodies, other
      neuropathies have been reported. In order to investigate the clinical and
      electrophysiological manifestations of neuropathies associated with anti-Hu
      antibodies, we conducted a retrospective study of 20 patients. For the
      electrophysiological study, each nerve was classified as normal, demyelinating,
      axonal/neuronal or axonal/demyelinating. Peripheral neuropathy was the presenting
      symptom in 95% of patients. CNS and autonomic neuropathy were present in 40% and
      30% of patients, respectively. The course of the neuropathy was acute, mimicking
      Guillain-Barre syndrome in one patient (5%), and subacute (55%) or progressive
      (40%) in the others. Clinically, the neuropathy was sensory (70%), sensorimotor
      (25%) or motor (5%). At onset, symptoms were symmetrical (65%), asymmetrical
      (25%) or multifocal (10%). Pain was a predominant manifestation (80%).
      Amyotrophia and fasciculations were rare. The median Rankin's score was 2, three
      patients having an indolent form. Electrophysiology showed the axonal/neuronal
      pattern to be the most frequent (46.9% of studied nerves); an
      axonal/demyelinating or demyelinating pattern being seen in 18.3% and 4.9% of
      nerves, respectively. The axonal/neuronal pattern was more frequent in sensory
      nerves and the mixed axonal/demyelinating pattern more frequent in motor nerves
      (P < 0.01). A higher proportion of abnormal nerves correlated with a progressive
      course (P < 0.05) or a Rankin's score between 3 and 5 (P < 0.01). In patients
      with sensory neuropathy, 88.5% of sensory nerves were abnormal, mostly with an
      axonal/neuronal pattern. In addition, 47% of motor nerves were abnormal so that
      only four out of 14 patients with a clinically pure sensory neuropathy (28.6%)
      had an electrophysiological pattern typical of sensory neuronopathy. In patients
      with a sensorimotor neuropathy, 96.6% of sensory and 71% of motor nerves were
      abnormal. The only statistical difference between sensory and sensorimotor
      neuropathies was that patients with sensorimotor neuropathy had more frequent
      motor nerve involvement (P < 0.05) without differences concerning the
      distribution of the abnormal patterns. Needle neuromyography showed only limited
      evidence of motor neurone degeneration in both sensory and sensorimotor
      neuropathy. The present work shows that the typical clinical and
      electrophysiological pattern of subacute sensory neuronopathy is rarely
      encountered in patients with anti-Hu antibody and that motor nerve involvement is
      frequently seen, even in the absence of a motor deficit. In addition to their
      potential pathophysiological involvement in the mechanism of the paraneoplastic
      neuropathy, these findings have practical consequences for the diagnosis of the
      disorder.

PMID- 11834603
TI  - Localization of arm representation in the corona radiata and internal capsule in
      the non-human primate.
AB  - Localization of the corticofugal projection in the corona radiata (CR) and
      internal capsule (IC) can assist in evaluating a patient's residual motor
      capacity following subtotal brain damage and predicting their potential for
      functional restitution. To advance our understanding of the organization of the
      corticofugal projection in this critical brain region, we studied the
      trajectories of the projection arising from six different cortical arm
      representations in rhesus monkeys. They included the arm representation of the
      primary (M1), ventral lateral pre- (LPMCv), dorsolateral pre- (LPMCd),
      supplementary (M2), rostral cingulate (M3) and caudal cingulate (M4) motor
      cortices. In the CR, each pathway was segregated as medial motor area fibres
      arched over the caudate and lateral motor area fibres arched over the putamen. In
      the IC, the individual corticofugal pathways were found to be widespread,
      topographically organized and partially overlapping. At superior levels of the
      IC, the corticofugal projection from the arm representation of M3 coursed through
      the middle and posterior portion of the anterior limb (ICa). The projection from
      M2 passed through the posterior portion of the ICa and the genu (ICg). The
      projection from LPMCv travelled through the genu and anterior portion of the
      posterior limb (ICp). The projection from LPMCd occupied the anterior portion of
      the ICp. The projection from M4 descended through the mid-portion of the ICp.
      Fibres from M1 also travelled in the ICp, positioned immediately posterior to the
      M4 projection. As each fibre system progressed inferiorly within the IC, all
      fibres shifted posteriorly to occupy the ICp. Within the ICp, the projections
      from M3, M2, LPMCv, LPMCd, M4 and M1 maintained their anterior to posterior
      orientation, respectively. M2, LPMCd and LPMCv fibres overlapped extensively, as
      did fibres from M4 and M1. Our data suggest that CR and superior capsular lesions
      may correlate with more favourable levels of functional recovery due to the
      widespread nature of arm representation. In contrast, the extensive overlap and
      comparatively condensed organization of arm representation at inferior capsular
      levels suggest that lesions seated inferiorly are likely to correlate with poorer
      levels of recovery of upper limb movement. Based on the relative density of
      corticospinal neurones associated with the motor areas studied, our findings also
      suggest that motor deficit severity is likely to increase as a lesion occupies
      progressively more posterior regions of the IC.

PMID- 11834604
TI  - Intraoperative mapping of the subcortical language pathways using direct
      stimulations. An anatomo-functional study.
AB  - Functional neuroimaging has improved pre-planning of surgery in eloquent cortical
      areas, but remains unable to map white matter. Thus, tumour resection in
      functional subcortical regions still presents a high risk of sequelae. The
      authors successfully used intraoperative electrical stimulations to perform
      subcortical language pathway mapping in order to avoid postoperative definitive
      deficit, and correlated these functional findings with the anatomical location of
      the eloquent bundles detected using postoperative MRI. At the same time, this
      also improved knowledge of fibre connectivity. Thirty patients harbouring a
      cortico-subcortical low-grade glioma in the left dominant hemisphere were
      operated on whilst awake using intraoperative electrical functional mapping
      during surgical resection. Language cortical sites and subcortical pathways were
      clearly identified and preserved in the 30 cases. The anatomo-functional
      correlations between data obtained using intraoperative subcortical mapping and
      postoperative MRI revealed the existence in all patients of common pathways which
      seem essential to language. This was shown by inducing reproducible speech
      disturbances during stimulations as follows: the subcallosal fasciculus
      (initiation disorders), the periventricular white matter (dysarthria), the
      arcuate fasciculus and the insular connections (anomia). Clinically, all patients
      except three presented a transient postoperative dysphasia, which resolved within
      3 months. On control MRI, 14 resections were total and 16 subtotal due to
      infiltration of functional bundles described above. It is recommended that the
      combination of the techniques as described could prove ideal for future non
      invasive reliable subcortical mapping both in healthy volunteers and in patients
      harbouring a (cortico)subcortical lesion in order to optimize surgical pre
      planning.

PMID- 11834605
TI  - Intracellular distribution of peroxynitrite during doxorubicin cardiomyopathy:
      evidence for selective impairment of myofibrillar creatine kinase.
AB  - Cardiac peroxynitrite and protein nitration are increased during doxorubicin
      cardiotoxicity, but the intracellular targets and functional consequences have
      not been defined. We investigated the intracellular distribution of protein
      nitration during doxorubicin cardiotoxicity in mice. Following in vivo cardiac
      function assessments by echocardiography, cardiac tissues were prepared for
      immunohistochemistry and electron microscopy 5 days after doxorubicin (20 mg kg(
      1)) or vehicle control. Increased cardiac 3-nitrotyrosine was observed using
      light microscopy in doxorubicin treated animals. Immunogold electron microscopy
      (55,000x) revealed increased myofibrillar and mitochondrial 3-nitrotyrosine
      levels following doxorubicin, but cellular 3-nitrotyrosine density was 2 fold
      higher in myofibrils. We therefore investigated the actions of peroxynitrite on
      intact cardiac contractile apparatus. Skinned ventricular trabeculae were exposed
      to physiologically relevant peroxynitrite concentrations (50 or 300 nM) for 1 h,
      then Ca(2+) induced contractile responses were measured in the presence of ATP (4
      mM) or phosphocreatine (12 mM) as high energy phosphate supplier. ATP maximal
      force generation was unaltered after 50 nM peroxynitrite, but phosphocreatine/ATP
      response was reduced (0.99+/-0.63 vs 1.59+/-0.11), suggesting selective
      inactivation of myofibrillar creatine kinase (MM-CK). Reduction of ATP maximal
      force was observed at 300 nM peroxynitrite and phosphocreatine/ATP response was
      further reduced (0.64+/-0.30). Western blotting showed concentration dependent
      nitration of MM-CK in treated trabeculae. Similarly, cardiac tissues from
      doxorubicin treated mice demonstrated increased nitration and inactivation of MM
      CK compared to controls. These results demonstrate that peroxynitrite-related
      protein nitration are mechanistic events in doxorubicin cardiomyopathy and that
      the cardiac myofibril is an important oxidative target in this setting.
      Furthermore, MM-CK may be a uniquely vulnerable target to peroxynitrite in vivo.

PMID- 11834606
TI  - A NO-releasing derivative of acetaminophen spares the liver by acting at several
      checkpoints in the Fas pathway.
AB  - NCX-701 is a nitric oxide (NO)-releasing acetaminophen (APAP) derivative. In the
      present study we demonstrated that NCX-701 is as effective as APAP in controlling
      body temperature in a rat model of endotoxin-induced fever. Liver toxicity is a
      major complication of APAP overdosing. To investigate whether NCX-701 is
      hepatotoxic, BALB/C mice were injected with 100 - 500 mg kg(-1) APAP or NCX-701
      alone or in combination (i.e. 500 mg kg(-1) of both compounds). Our results
      demonstrated that although APAP caused a dose-dependent liver injury, NCX-701 was
      completely devoid of liver toxicity. At the dose of 500 mg kg(-1) APAP caused an
      approximately 40 fold increase of AST plasma levels and extensive centrilobular
      necrosis. APAP and NCX-701 share the same metabolic pathway as demonstrated by
      the time-course of APAP-glucuronide concentrations in plasma and liver. NCX-701
      was safe in mice with pre-existing chronic liver disease. Indeed, while C57BL6
      transgenic mice expressing the hepatitis B virus (HBV) at the age of 8 months
      were significantly more susceptible to liver damage induced by APAP (500 mg kg(
      1)) than their congenic littermates, treating HBV-transgenic mice with NCX-701,
      500 mg kg(-1), caused no damage. Co-administration of NCX-701 at the dose 500 mg
      kg(-1) to mice treated with APAP, 500 mg kg(-1), completely protected against
      liver damage induced by APAP. APAP, but not NCX-701, upregulated liver Fas and
      Fas Ligand mRNA expression in vivo. Incubating mouse hepatocytes with APAP, but
      not with NCX-701, increased cell surface Fas expression and sensitized
      hepatocytes to death induced by challenge with a Fas-agonistic antibody.
      Collectively, these observations suggest that APAP toxicity is Fas mediated and
      that NCX-701 spares the liver by acting at several checkpoints in the Fas
      pathway.

PMID- 11834607
TI  - Distribution of alpha-1 adrenoceptor subtypes in RNA and protein in rabbit eyes.
AB  - We investigated subtypes of alpha-1 adrenoceptor (AR) in rabbit ocular tissues
      using reverse transcription-polymerase chain reaction (RT - PCR), in situ
      hybridization (ISH) and binding studies. Competitive RT - PCR assays specific for
      the subtypes of alpha-1 AR revealed that the mRNA expression of alpha-1a AR was
      dominant, and that of each alpha-1b and alpha-1d was less than 10% and 0.5% of
      total alpha-1 ARs mRNA, respectively, in the iris, ciliary body, choroid and
      retina. In alpha-1a AR splice isoform-specific RT - PCR assays, we found a
      distinct proportion of each isoform mRNA in the iris, ciliary body and choroid.
      The results of the ISH assays for alpha-1a AR subtype showed that hybridization
      signals were clearly observed in the iris dilator muscle and in the epithelium of
      the ciliary processes. In binding studies, alpha-1A AR was a dominant subtype in
      the iris, choroid and retina in contrast to the ciliary body that had more alpha
      1B than alpha-1A AR subtype at protein level.

PMID- 11834608
TI  - Phosphodiesterase isoenzyme families in human osteoarthritis chondrocytes-
      functional importance of phosphodiesterase 4.
AB  - We studied whether selective inhibitors of cyclic nucleotide hydrolysing
      phosphodiesterase (PDE) isoenzymes influence IL-1beta-induced nitric oxide (NO)
      release from human articular chondrocytes. In addition, the pattern of PDE
      isoenzymes contributing to cyclic nucleotide hydrolysis in human chondrocytes was
      characterized. Chondrocytes were isolated from human osteoarthritic cartilage and
      cultured in alginate beads. IL-1beta-induced chondrocyte products (nitric oxide
      and prostaglandin E(2)) were measured in culture supernatants after 48 h
      incubation time. PDE activities were assessed in chondrocyte lysates. Inducible
      nitric oxide synthase (iNOS) and PDE4A-D proteins were detected by
      immunoblotting. The selective PDE4 inhibitors Piclamilast and Roflumilast
      partially attenuated IL-1beta-induced NO production whereas selective inhibitors
      of PDE2 (EHNA), PDE3 (Motapizone) or PDE5 (Sildenafil) were inactive.
      Indomethacin reversed the reduction of IL-1beta-induced NO by PDE4 inhibitors. It
      was shown that autocrine prostaglandin E(2) (PGE(2)) enabled PDE4 inhibitors to
      reduce IL-1beta-induced NO in this experimental setting. Major PDE4 and PDE1
      activities were identified in chondrocyte lysates whereas only minor activities
      of PDE2, 3 and 5 were found. IL-1beta and cyclic AMP-mimetics upregulated PDE4
      activity and this was associated with an augmentation of PDE4B2 protein. Based on
      the view that nitric oxide contributes to cartilage degradation in osteoarthritis
      our study suggests that PDE4 inhibitors may have chondroprotective effects.

PMID- 11834609
TI  - Inducing the cell cycle arrest and apoptosis of oral KB carcinoma cells by
      hydroxychavicol: roles of glutathione and reactive oxygen species.
AB  - Hydroxychavicol (HC; 10 - 50 microM), a betel leaf component, was found to
      suppress the 2% H(2)O(2)-induced lucigenin chemiluminescence for 53 - 75%. HC
      (0.02 - 2 microM) was also able to trap superoxide radicals generated by a
      xanthine/xanthine oxidase system with 38 - 94% of inhibition. Hydroxyl radicals
      induced PUC18 plasmid DNA breaks was prevented by HC (1.6 - 16 microM). A 24-h
      exposure of KB cells to HC (0.5, 1 mM) resulted in 54 - 74% cell death as
      analysed by a 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl-tetrazolium bromide
      (MTT) assay. HC (10, 50 microM) further suppressed the growth of KB cells (15 and
      76%, respectively). Long-term colony formation of KB cells was inhibited by 51%
      with 10 microM HC. Pretreatment of KB cells with 100 microM HC inhibited the
      attachment of KB cells to type I collagen and fibronectin by 59 and 29%,
      respectively. Exposure of KB cells to 0.1 mM HC for 24 h resulted in cell cycle
      arrest at late S and G2/M phase. Increasing the HC concentration to 0.25 and 0.5
      mM led to apoptosis as revealed by detection of sub-G(0)/G(1) peaks with a
      concomitant decrease in the number of cells residing in late S and G(2)/M phase.
      Inducing the apoptosis of KB cells by HC was accompanied by marked depletion in
      reduced form of GSH (>0.2 mM) and the increasing of reactive oxygen species
      production (>0.1 mM) as analysed by CMF- and DCF-single cell fluorescence flow
      cytometry. These results indicate that HC exerts antioxidant property at low
      concentration. HC also inhibits the growth, adhesion and cell cycle progression
      of KB cells, whereas its induction of KB cell apoptosis (HC>0.1 mM) was
      accompanied by cellular redox changes.

PMID- 11834611
TI  - Spontaneous phasic activity of the pig urinary bladder smooth muscle:
      characteristics and sensitivity to potassium channel modulators.
AB  - A hallmark for unstable bladder contractions is hyperexcitability and changes in
      the nature of spontaneous phasic activity of the bladder smooth muscle. In this
      study, we have characterized the spontaneous activity of the urinary bladder
      smooth muscle from the pig, a widely used model for studying human bladder
      function. Our studies demonstrate that phasic activity of the pig detrusor is
      myogenic and is influenced by the presence of urothelium. Denuded strips exhibit
      robust spontaneous activity measured as mean area under the contraction curve
      (AUC=188.9+/-15.63 mNs) compared to intact strips (AUC=7.3+/-1.94 mNs).
      Spontaneous phasic activity, particularly the amplitude, is dependent on both
      calcium entry through voltage-dependent calcium channels and release from
      ryanodine receptors as shown by inhibition of spontaneous activity by nifedipine
      and ryanodine respectively. Inhibition of BK(Ca) channels by iberiotoxin (100 nM)
      resulted in an increase in contraction amplitude (89.1+/-20.4%) and frequency
      (92.5+/-31.0%). The SK(Ca) channel blocker apamin (100 nM) also increased
      contraction amplitude (69.1+/-24.3%) and frequency (53.5+/-13.6%) demonstrating
      that these mechanisms are critical to the regulation of phasic spontaneous
      activity. Inhibition of K(ATP) channels by glyburide (10 microM) did not
      significantly alter myogenic contractions (AUC=18.5+/-12.3%). However, K(ATP)
      channel openers (KCOs) showed an exquisite sensitivity for suppression of
      spontaneous myogenic activity. KCOs were generally 15 fold more potent in
      suppressing spontaneous activity compared to contractions evoked by electrical
      field-stimulation. These studies suggest that potassium channel modulation,
      particularly K(ATP) channels, may offer a unique mechanism for controlling
      spontaneous myogenic activity especially those associated with the
      hyperexcitability occurring in unstable bladders.

PMID- 11834610
TI  - Contribution of cytochrome P450 metabolites to bradykinin-induced vasodilation in
      endothelial NO synthase deficient mouse hearts.
AB  - We have characterized the contribution of endothelial nitric oxide synthase
      (eNOS), cyclo-oxygenase (COX) and cytochrome P450 (CYP450) to the bradykinin (BK)
      induced vasodilation in isolated hearts from wildtype (WT) and eNOS deficient
      mice (eNOS-/-). The endothelium-dependent vasodilation by bradykinin (BK, 1
      microM) was significantly lower in eNOS-/- hearts than that in WT hearts (+247%
      and +325% of basal flow, respectively), while there was no difference in the
      endothelium-independent vasodilation by adenosine. In WT hearts, the BK-induced
      vasodilation was markedly attenuated following inhibition of NOS with ETU (10
      microM) but not after COX inhibition with diclofenac (3 microM) (P<0.01). In line
      with this finding, Bk did not increase the cardiac prostacyclin release as
      measured by ELISA for 6-keto-PGF1alpha in the coronary venous effluent. In eNOS-/
      hearts, the flow response to BK was insensitive to both NOS and COX inhibition.
      The NOS/COX-independent vasodilatory factor which remained under L-NMMA+DF
      application was almost completely eliminated by either clotrimazole (3 microM),
      miconazole (0.5 microM) or 17-ODYA (1 microM), suggesting that it was a
      metabolite of CPY450 enzymes. Sulfaphenazole (10 microM), a CYP450 2C inhibitor,
      exerted only a minimal inhibitory effect. In eNOS-/- hearts the effect of CYP450
      inhibitors on the BK response was significantly more pronounced than in WT
      hearts, indicating an enhanced contribution of CYP450 enzymes. These findings
      suggest that in isolated mouse hearts the BK-induced vasodilation is mediated by
      NO and CYP450 metabolites but not by prostaglandins. The CYP450 dependent
      vasodilator was was functionally up-regulated in eNOS-/- hearts and thus likely
      to compensate for the loss of eNOS in the coronary circulation.

PMID- 11834612
TI  - The effect of 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') and its
      metabolites on neurohypophysial hormone release from the isolated rat
      hypothalamus.
AB  - Methylenedioxymethamphetamine (MDMA, 'ecstasy'), widely used as a recreational
      drug, can produce hyponatraemia. The possibility that this could result from
      stimulation of vasopressin by MDMA or one of its metabolites has been
      investigated in vitro. Release of both oxytocin and vasopressin from isolated
      hypothalami obtained from male Wistar rats was determined under basal conditions
      and following potassium (40 mM) stimulation. The results were compared with those
      obtained for basal and stimulated release in the presence of MDMA or metabolites
      in the dose range 1 microM to 100 pM (n=5 - 8) using Student's t-test with
      Dunnett's correction for multiple comparisons. All compounds tested affected
      neurohypophysial hormone release, HMMA (4-hydroxy-3-methoxymethamphetamine) and
      DHA (3,4-dihydroxyamphetamine) being more active than MDMA, and DHMA (3,4
      dihydroxymethamphetamine) being the least active. The effect on vasopressin
      release was greater than that on oxytocin. In the presence of HMMA the ratio
      test:control for basal release increased for vasopressin from 1.1+/-0.16 to 2.7+/
      0.44 (s.e.m., P<0.05) at 10 nM and for oxytocin from 1.0+/-0.05 to 1.6+/-0.12 in
      the same hypothalami. For MDMA the ratio increased to 1.5+/-0.27 for vasopressin
      and to 1.28+/-0.04 for oxytocin for 10 nM. MDMA and its metabolites can stimulate
      both oxytocin and vasopressin release in vitro, the response being dose dependent
      for each drug with HMMA being the most potent.

PMID- 11834613
TI  - Effects of cardioselective KATP channel antagonism on basal, stimulated, and
      ischaemic myocardial function in in vivo failing canine heart.
AB  - Inhibition of cardiomyocyte-specific ATP-sensitive potassium (K(ATP)) channels
      prolongs the action potential during intense ischaemia with attendant
      antiarrhythmic effects. However, this is accompanied by contractile depression in
      some models. These changes may be particularly troublesome in dilated
      cardiomyopathic hearts that display basal systolic dysfunction, limited energy
      reserve, and prolonged repolarization favouring arrhythmia. Mechanical effects of
      selective myocyte K(ATP) channel blockade on basal, beta-adrenergic stimulated,
      and ischemic responses were therefore tested in dogs with cardiac failure induced
      by tachypacing. Cardiovascular function was assessed by pressure - dimension
      relationships in 10 conscious, chronically instrumented dogs
      (sonomicrometry/micromanometry), with or without cardiac failure. Cardiomyocyte
      K(ATP) channels were inhibited by HMR 1098, and data obtained under basal
      conditions, during epinephrine infusion to raise metabolic demand, during
      regional ischaemia, and with combined ischaemia+epinephrine. HMR 1098 had no
      effect on baseline cardiac function nor did it induce arrhythmia in normal or
      failing hearts. Epinephrine raised cardiac work 65% and oxygen consumption 55%,
      yet HMR 1098 had no functional effect in either heart condition. Regional
      ischaemia with or without epinephrine co-stimulation depressed regional and
      global function, yet both were also unaffected by HMR 1098. There was minimal
      arrhythmia without HMR 1098, and drug infusion did not alter this. Thus, myocyte
      K(ATP) channels play a negligible role modulating intact in vivo cardiac
      contraction or arrhythmia in normal and failing heart with and without increased
      metabolic demand and/or regional ischaemia. This supports the feasibility of
      administering such agents to depressed hearts, despite underlying contractile and
      electrophysiologic abnormalities.

PMID- 11834614
TI  - Agmatine, an endogenous ligand at imidazoline binding sites, does not antagonize
      the clonidine-mediated blood pressure reaction.
AB  - Since agmatine has been identified as a clonidine displacing substance (CDS), the
      aim of this study was to investigate whether agmatine can mimic CDS-induced
      cardiovascular reactions in organ bath experiments, pithed spontaneously
      hypertensive rats (SHR) and anaesthetized SHR. Intravenously-administered
      agmatine significantly reduced the blood pressure and heart rate of anaesthetized
      SHR at doses higher than 1 and 3 mg kg(-1), respectively. These effects are
      probably mediated via central mechanisms, since there was an approximate 8 fold
      rightward shift of the dose-response curve in the pithed SHR (indicating a
      weakened cardiovascular effect). Moreover, in organ bath experiments, agmatine
      failed to alter the contractility of intact or endothelium-denuded aortal rings.
      When agmatine was administered i.c.v. to anaesthetized SHR, blood pressure was
      increased without any alteration of heart rate, whereas blood pressure was
      unchanged and heart rate was increased after injection into the 4th brain
      ventricle. This suggests that haemodynamic reaction patterns after central
      application are related to distinct influences on central cardiovascular
      mechanisms. Agmatine reduces noradrenaline release in pithed SHR while alpha(2)
      adrenoceptors are irreversibly blocked with phenoxybenzamine, but not while I(1)
      binding sites are selectively blocked with AGN192403. This suggests that agmatine
      may modulate noradrenaline release in the same way that clonidine does, i.e. via
      imidazoline binding sites; this involves a reduction in sympathetic tone which in
      turn reduces blood pressure and heart rate. Finally, CDS-like cardiovascular
      activity appears not to be due to agmatine, since (i) blood pressure in
      anaesthetized SHR is decreased by agmatine and clonidine, and (ii) agmatine did
      not antagonize the blood pressure reaction to clonidine in pithed or
      anaesthetized SHR.

PMID- 11834616
TI  - Evidence for an atypical receptor mediating the augmented bronchoconstrictor
      response to adenosine induced by allergen challenge in actively sensitized Brown
      Norway rats.
AB  - The bronchoconstrictor response to adenosine is markedly and selectively
      increased following ovalbumin (OA) challenge in actively sensitized, Brown Norway
      rats. We present a pharmacological analysis of the receptor mediating this
      response. Like adenosine, the broad-spectrum adenosine receptor agonist, NECA,
      induced dose-related bronchoconstriction in actively sensitized, OA-challenged
      animals. In contrast, CPA, CGS 21680 and 2-Cl-IB-MECA, agonists selective for
      A(1) A(2A) and A(3) receptors, respectively, induced no, or minimal,
      bronchoconstriction. Neither the selective A(1) receptor antagonist, DPCPX, nor
      the selective A(2A) receptor antagonist, ZM 241385, blocked the
      bronchoconstrictor response to adenosine. MRS 1754, which has similar affinity
      for rat A(2B) and A(1) receptors, failed to block the bronchoconstrictor response
      to adenosine despite blockade of the A(1) receptor-mediated bradycardia induced
      by NECA. 8-SPT and CGS 15943, antagonists at A(1), A(2A), and A(2B) but not A(3)
      receptors, inhibited the bronchoconstrictor response to adenosine. However, the
      degree of blockade (approximately 3 fold) did not reflect the plasma
      concentrations, which were 139 and 21 times greater than the K(B) value at the
      rat A(2B) receptor, respectively. Adenosine and NECA, but not CPA, CGS 21680 or 2
      Cl-IB-MECA, induced contraction of parenchymal strip preparations from actively
      sensitized OA-challenged animals. Responses to adenosine could not be antagonized
      by 8-SPT or MRS 1754 at concentrations >50 times their affinities at the rat
      A(2B) receptor. The receptor mediating the bronchoconstrictor response to
      adenosine augmented following allergen challenge in actively sensitized BN rats
      cannot be categorized as one of the four recognized adenosine receptor subtypes.

PMID- 11834615
TI  - Inhibition of adenylyl cyclase by neuronal P2Y receptors.
AB  - P2Y receptors inhibiting adenylyl cyclase have been found in blood platelets,
      glioma cells, and endothelial cells. In platelets and glioma cells, these
      receptors were identified as P2Y(12). Here, we have used PC12 cells to search for
      adenylyl cyclase inhibiting P2Y receptors in a neuronal cellular environment. ADP
      and ATP (0.1 - 100 microM) left basal cyclic AMP accumulation unaltered, but
      reduced cyclic AMP synthesis stimulated by activation of endogenous A(2A) or
      recombinant beta(2) receptors. Forskolin-dependent cyclic AMP production was
      reduced by <or=1 microM and enhanced by 10 - 100 microM ADP; this latter effect
      was turned into an inhibition when A(2A) receptors were blocked. The nucleotide
      inhibition of cyclic AMP synthesis was not altered when P2X receptors were
      blocked, but abolished by pertussis toxin. The rank order of agonist potencies
      for the reduction of cyclic AMP was (IC(50) values): 2-methylthio-ADP (0.12 nM)=2
      methylthio-ATP (0.13 nM)>ADPbetaS (71 nM)>ATP (164 nM)=ADP (244 nM). The
      inhibition by ADP was not antagonized by suramin, pyridoxal-phosphate-6-azophenyl
      2',4'-disulphonic acid, or adenosine-3'-phosphate-5'-phosphate, but attenuated by
      reactive blue 2, ATP(alpha)S, and 2-methylthio-AMP. RT - PCR demonstrated the
      expression of P2Y(2), P2Y(4), P2Y(6), and P2Y(12), but not P2Y(1), receptors in
      PC12 cells. In Northern blots, only P2Y(2) and P2Y(12) were detectable.
      Differentiation with NGF did not alter these hybridization signals and left the
      nucleotide inhibition of adenylyl cyclase unchanged. We conclude that P2Y(12)
      receptors are expressed in neuronal cells and inhibit adenylyl cyclase activity.

PMID- 11834617
TI  - Alpha 2-adrenoceptors in the enteric nervous system: a study in alpha 2A
      adrenoceptor-deficient mice.
AB  - Mammals possess three types of alpha(2)-adrenoceptor, alpha(2A), alpha(2B) and
      alpha(2C). Our aim was to determine the type of alpha(2)-adrenoceptor involved in
      the control of gastrointestinal motility. In transmitter overflow experiments,
      myenteric plexus longitudinal muscle (MPLM) preparations of the ileum were
      preincubated with [(3)H]-choline and then superfused. The alpha(2)-adrenoceptor
      agonist medetomidine reduced the electrically evoked overflow of tritium from
      preparations taken from wild type but not alpha(2A)-adrenoceptor-knockout mice.
      In a second series of overflow experiments, MPLM preparations were preincubated
      with [(3)H]-noradrenaline and then superfused. Again medetomidine reduced the
      electrically evoked overflow of tritium from wild type but not alpha(2A)-knockout
      preparations. In organ bath experiments, medetomidine reduced electrically evoked
      contractions of segments of the ileum from wild type but not alpha(2A)-knockout
      mice. In each of these three series, phentolamine antagonized the effect of
      medetomidine in wild-type preparations with greater potency than rauwolscine. In
      conscious mice, gastrointestinal transit was assessed by means of an intragastric
      charcoal bolus. In alpha(2A)-knockout mice, the speed of gastrointestinal transit
      was doubled compared to wild-type. Medetomidine, injected intraperitoneally,
      slowed gastrointestinal transit in wild type but not alpha(2A)-knockout mice. We
      conclude that the cholinergic motor neurons of the enteric nervous system of mice
      possess alpha(2)-heteroreceptors which mediate inhibition of acetylcholine
      release, of neurogenic contractions and of gastrointestinal transit. The
      noradrenergic axons innervating the intestine possess alpha(2)-autoreceptors.
      Both hetero- and autoreceptors are exclusively alpha(2A). It is the alpha(2A)
      adrenoceptor which in vivo mediates the inhibition of intestinal motility by the
      sympathetic nervous system.

PMID- 11834618
TI  - Pharmacological characterization of a non-inactivating outward current observed
      in mouse cerebellar Purkinje neurones.
AB  - Whole-cell patch clamp recordings were used to investigate the properties of a
      non-inactivating outward current observed in mouse cerebellar Purkinje neurones
      at a holding potential of -20 mV. Increasing the external potassium (K(+))
      concentration from 3 mM to 20 mM produced a rightward shift in the observed
      reversal potential of approximately 30 mV or approximately 40 mV for a K(+)-or a
      caesium (Cs(+))-based intracellular solution respectively, indicating the outward
      current was a K(+) current. The outward current was partially inhibited by the
      K(+) channel blocker, tetraethylammonium (TEA; IC(50)=0.15 mM). Subsequently, the
      background or TEA-insensitive current was measured in the presence of 1 mM TEA.
      The background current was reversibly inhibited by barium (Ba(2+); 300 microM,
      50%) and potentiated by the application of arachidonic acid (AA; 1 mM, 62%). The
      volatile anaesthetic, halothane (1 mM), and the neuroprotectant, riluzole (500
      microM), both reversibly inhibited the background current by 54% and 36%
      respectively. The background current was insensitive to changes in both
      intracellular and extracellular acidification. The GABA(B) and mu-opioid receptor
      agonists, baclofen and [D-Ala(2), N-MePhe(4)-Gly-ol(5)] enkephalin (DAMGO) both
      reversibly potentiated the outward current by 42% and 26% respectively. In
      contrast, the metabotropic glutamate receptor and acetylcholine receptor
      agonists, (S)-3,5-dihydroxyphenylglycine (DHPG) and muscarine both reversibly
      inhibited the outward current by 48% and 42% respectively. These data suggest
      that cerebellar Purkinje neurones possess a background current which shares
      several properties with recently cloned two-pore K(+) channels, particularly THIK
      1.

PMID- 11834619
TI  - Pirlindole and dehydropirlindole protect rat cultured neuronal cells against
      oxidative stress-induced cell death through a mechanism unrelated to MAO-A
      inhibition.
AB  - It has been shown that the MAO (monoamine oxidase)-B inhibitor deprenyl (DPR,
      selegiline) protects some cell types against oxidative stress. By decreasing
      H(2)O(2) production, MAO-A inhibitors could also reduce oxidative stress. This
      study reports the effect of the MAO-A inhibitors, pirlindole (PIR),
      dehydropirlindole (DHP), brofaromine (BRO) and moclobemide (MCL) on primary
      cultured brain cells exposed to iron-mediated toxicity. A comparison with trolox
      (TRO), a hydrosoluble vitamin-E analogue that protects against such an induced
      stress, was performed. Rat hippocampal or cortical cultured cells were exposed
      either to 2 microM FeSO(4) alone or in the presence of PIR, DHP, BRO, DPR, MCL or
      TRO. Cell survival (lactate-dehydrogenase measurements, 16 h incubation),
      intracellular peroxide production (DCF-fluorescence, 1 h incubation),
      lipoperoxidation (TBARS-fluorescence, 6 h incubation) and mitochondrial function
      (MTT-test, 16 h incubation) were assessed. PIR, DHP and TRO significantly
      protected cultures (P<0.05) against Fe(2+)-induced toxicity in a concentration
      dependent manner. The EC(50s) of these compounds were 6, 12 and 19 microM,
      respectively, in hippocampal cells. For cortical cell cultures incubated in the
      presence of iron and PIR or DHP, EC(50s) were 5 and 6 microM respectively. All
      Hill coefficients were close to unity. BRO, MCL and DPR were not protective in
      any type of culture. The IC(50s) for the inhibition of MAO-A were 2, 2 and 0.2
      microM for PIR, DHP and BRO, respectively. PIR, DHP and TRO, but not DPR, induced
      a significant decrease in both intracellular peroxide production and
      lipoperoxidation. They also improved mitochondrial function. These experiments
      show that PIR and DHP can protect hippocampal and cortical neurons against
      oxidative stress at pharmacologically relevant concentrations. This protective
      effect seems unrelated to inhibition of MAO-A, but possibly involves free radical
      scavenging.

PMID- 11834620
TI  - Caffeine-induced immobilization of gating charges in isolated guinea-pig
      ventricular heart cells.
AB  - The effects of 10 mM caffeine (CAF) on intramembrane charge movements (ICM) were
      studied in isolated guinea-pig ventricular heart cells with the whole-cell patch
      clamp technique. In the presence of CAF, the properties (voltage dependence,
      maximum Q(ON) [Q(max)], availability with voltage) of Q(ON) charge activated from
      -110 mV were barely affected. Following a 100 ms prepulse to -50 mV to decrease
      the participation of charges originating from Na channels, the voltage dependence
      of Q(ON) was shifted by 5 mV (negative component) and by 10 mV (positive
      component) towards negative potentials, and Q(max) was depressed by 16.5%. CAF
      drastically reduced in a time- and voltage-dependent manner Q(OFF) on
      repolarization to -50 mV, the effects being greater at positive potentials. CAF
      induced Q(OFF) immobilization could be almost entirely removed by repolarization
      to voltages as negative as -170 mV. In these conditions, the voltage-dependence
      of Q(OFF) (repolarization to +30 to -170 mV) was shifted by 17 mV (negative
      component) and 30 mV (positive component) towards negative potentials, suggesting
      an interconversion into charge 2. Most of CAF effects were suppressed when the
      sarcoplasmic reticulum (SR) was not functional or when the cells were loaded with
      BAPTA-AM. We conclude that CAF effects on ICM are likely due to Ca(2+) ions
      released from the SR, and which accumulate in the subsarcolemmal fuzzy spaces in
      the vicinity of the Ca channels. Because CAF effects were more pronounced on
      Q(OFF) than on Q(ON) the channels have likely to open before Ca(2+) ions could
      affect their gating properties. It is speculated that such an effect on gating
      charges might contribute to the Ca-induced inactivation of the Ca current.

PMID- 11834621
TI  - Testosterone-induced vasorelaxation in the rat mesenteric arterial bed is
      mediated predominantly via potassium channels.
AB  - We have investigated the involvement of nitric oxide and K(+) channels in the
      vasorelaxant responses to physiologically-relevant concentrations of testosterone
      in the rat isolated mesenteric arterial bed. Testosterone (100 pM - 10 microM)
      elicited concentration-dependent relaxations in the isolated mesenteric arterial
      bed (pEC(50)=9.47 (9.22 - 9.73, 95% CI), maximal relaxation, R(max)=62.8+/-2.0%,
      n=6). A nitric oxide synthase (NOS) inhibitor, N(G)-nitro-L-arginine methyl ester
      (L-NAME, 300 microM) or removal of the endothelium significantly inhibited
      maximal relaxations to testosterone (L-NAME: R(max)=51.4+/-1.1%, P<0.01, n=6;
      endothelium-denuded: R(max)=46.9+/-2.8%, P<0.001, n=5). Raising the extracellular
      K(+) concentration to 30 and 60 mM, or pre-treatment with 300 microM
      tetrabutylammonium chloride (TBA), a calcium-activated K(+) channel inhibitor,
      abolished vasorelaxations induced by testosterone. A selective inhibitor of ATP
      sensitive K(+) (K(ATP)) channels, glibenclamide (10 microM) and an inhibitor of
      voltage-sensitive K(+) (K(V)) channels, 4-aminopyridine (4-AP, 1 mM) did not
      affect testosterone-induced responses. Vasorelaxation to 1 microM testosterone
      was significantly (P<0.05) inhibited by 100 nM charybdotoxin (ChTx), an inhibitor
      of large conductance calcium-activated K(+) (BK(Ca)) channels (control: 63.3+/
      9.9%, n=6; ChTx: 11.9+/-12.7%, n=3). Neither the testosterone receptor
      antagonist, flutamide (10 microM) nor an aromatase inhibitor, aminoglutethimide
      (10 microM) inhibited testosterone-induced responses. In conclusion, the present
      findings demonstrate, in the rat isolated mesenteric arterial bed, that
      testosterone causes acute vasorelaxations at physiologically relevant
      concentrations which are, in part, mediated via NO- and endothelium-dependent
      pathways. However, the activation of BK(Ca) channels plays a substantial role in
      testosterone-induced vasorelaxation.

PMID- 11834622
TI  - Involvement of mu- and kappa-, but not delta-, opioid receptors in the
      peristaltic motor depression caused by endogenous and exogenous opioids in the
      guinea-pig intestine.
AB  - Opiates inhibit gastrointestinal propulsion, but it is not clear which opioid
      receptor types are involved in this action. For this reason, the effect of opioid
      receptor - selective agonists and antagonists on intestinal peristalsis was
      studied. Peristalsis in isolated segments of the guinea-pig small intestine was
      triggered by a rise of the intraluminal pressure and recorded via the
      intraluminal pressure changes associated with the peristaltic waves. Mu-opioid
      receptor agonists (DAMGO, morphine), kappa-opioid receptor agonists (ICI-204,448
      and BRL-52,537) and a delta-opioid receptor agonist (SNC-80) inhibited
      peristalsis in a concentration-related manner as deduced from a rise of the
      peristaltic pressure threshold (PPT) and a diminution of peristaltic
      effectiveness. Experiments with the delta-opioid receptor antagonists naltrindole
      (30 nM) and HS-378 (1 microM), the kappa-opioid receptor antagonist nor
      binaltorphimine (30 nM) and the mu-opioid receptor antagonist cyprodime (10
      microM) revealed that the antiperistaltic effect of ICI-204,448 and BRL-52,537
      was mediated by kappa-opioid receptors and that of morphine and DAMGO by mu
      opioid receptors. In contrast, the peristaltic motor inhibition caused by SNC-80
      was unrelated to delta-opioid receptor activation. Cyprodime and nor
      binaltorphimine, but not naltrindole and HS-378, were per se able to stimulate
      intestinal peristalsis as deduced from a decrease in PPT. The results show that
      the neural circuits controlling peristalsis in the guinea-pig small intestine are
      inhibited by endogenous and exogenous opioids acting via mu- and kappa-, but not
      delta-, opioid receptors.

PMID- 11834623
TI  - Inhibition of cardiac Na+ current by primaquine.
AB  - The electrophysiological effects of the anti-malarial drug primaquine on cardiac
      Na(+) channels were examined in isolated rat ventricular muscle and myocytes. In
      isolated ventricular muscle, primaquine produced a dose-dependent and reversible
      depression of dV/dt during the upstroke of the action potential. In ventricular
      myocytes, primaquine blocked I(Na)(+) in a dose-dependent manner, with a K(d) of
      8.2 microM. Primaquine (i) increased the time to peak current, (ii) depressed the
      slow time constant of I(Na)(+) inactivation, and (iii) slowed the fast component
      for recovery of I(Na)(+) from inactivation. Primaquine had no effect on: (i) the
      shape of the I - V curve, (ii) the reversal potential for Na(+), (iii) the steady
      state inactivation and g(Na)(+) curves, (iv) the fast time constant of
      inactivation of I(Na)(+), and (v) the slow component of recovery from
      inactivation. Block of I(Na)(+) by primaquine was use-dependent. Data obtained
      using a post-rest stimulation protocol suggested that there was no closed channel
      block of Na(+) channels by primaquine. These results suggest that primaquine
      blocks cardiac Na(+) channels by binding to open channels and unbinding either
      when channels move between inactivated states or from an inactivated state to a
      closed state. Cardiotoxicity observed in patients undergoing malaria therapy with
      aminoquinolines may therefore be due to block of Na(+) channels, with subsequent
      disturbances of impulse conductance and contractility.

PMID- 11834624
TI  - Nociceptin/orphanin FQ inhibits capsaicin-induced guinea-pig airway contraction
      through an inward-rectifier potassium channel.
AB  - Nociceptin/orphanin FQ (N/OFQ), an endogenous opioid-like orphan receptor (NOP
      receptor, previously termed ORL1 receptor) agonist, has been found to inhibit
      capsaicin-induced bronchoconstriction in isolated guinea-pig lungs and in vivo.
      The underlying mechanisms are not clear. In the present studies, we tested the
      effect of N/OFQ on VR1 channel function in isolated guinea-pig nodose ganglia
      cells. Capsaicin increased intracellular Ca(2+) concentration in these cells
      through activation of vanilloid receptors. Capsaicin-induced Ca(2+) responses
      were attenuated by pretreatment of nodose neurons with N/OFQ (1 microM). N/OFQ
      inhibitory effect on the Ca(2+) response in nodose ganglia cells was antagonized
      by tertiapin (0.5 microM), an inhibitor of inward-rectifier K(+) channels, but
      not by verapamil, a voltage gated Ca(2+) channel blocker, indicating that an
      inward-rectifier K(+) channel is involved in N/OFQ inhibitory effect. In isolated
      guinea-pig bronchus, N/OFQ (1 microM) inhibited capsaicin-induced airway
      contraction. Tertiapin (0.5 microM) abolished the N/OFQ inhibition of capsaicin
      induced bronchial contraction. Capsaicin (10 microg) increased pulmonary
      inflation pressure in the isolated perfused guinea-pig lungs. This response was
      significantly attenuated by pretreatment with N/OFQ (1 microM). Tertiapin also
      abolished the N/OFQ inhibitory effect on capsaicin-induced bronchoconstriction in
      perfused lungs. Capsaicin increased the release of substance P and neurokinin A
      from isolated lungs. N/OFQ (1 microM) blocked the capsaicin-induced tachykinin
      release. These results indicate that N/OFQ-induced hyperpolarization of
      tachykinin containing airway sensory nerves, through an inward-rectifier K(+)
      channel activation, accounts for the inhibition of capsaicin-evoked
      broncoconstriction.

PMID- 11834625
TI  - Alterations in phenylephrine-induced contractions and the vascular expression of
      Na+,K+-ATPase in ouabain-induced hypertension.
AB  - Hypertension development, phenylephrine-induced contraction and Na(+),K(+)-ATPase
      functional activity and protein expression in aorta (AO), tail (TA) and superior
      mesenteric (SMA) arteries from ouabain- (25 microg day(-1), s.c., 5 weeks) and
      vehicle-treated rats were evaluated. Ouabain treatment increased systolic blood
      pressure (127+/-1 vs 160+/-2 mmHg, n=24, 35; P<0.001) while the maximum response
      to phenylephrine was reduced (P<0.01) in AO (102.8+/-3.9 vs 67.1+/-10.1% of KCl
      response, n=12, 9) and SMA (82.5+/-7.5 vs 52.2+/-5.8%, n=12, 9). Endothelium
      removal potentiated the phenylephrine response to a greater extent in segments
      from ouabain-treated rats. Thus, differences of area under the concentration
      response curves (dAUC) in endothelium-denuded and intact segments for control and
      ouabain-treated rats were, respectively: AO, 56.6+/-9.6 vs 198.3+/-18.3 (n=9, 7);
      SMA, 85.5+/-15.4 vs 165.4+/-24.8 (n=6, 6); TA, 13.0+/-6.1 vs 39.5+/-10.4% of the
      corresponding control AUC (n=6, 6); P<0.05. The relaxation to KCl (1 - 10 mM) was
      similar in segments from both groups. Compared to controls, the inhibition of 0.1
      mM ouabain on KCl relaxation was greater in AO (dAUC: 64.8+/-4.6 vs 84.0+/-5.1%,
      n=11, 14; P<0.05), similar in SMA (dAUC: 39.1+/-3.9 vs 43.3+/-7.8%, n=6, 7;
      P>0.05) and smaller in TA (dAUC: 62.1+/-5.5 vs 41.4+/-8.2%, n=12, 13; P<0.05) in
      ouabain-treated rats. Protein expression of both alpha(1) and alpha(2) isoforms
      of Na(+),K(+)-ATPase was augmented in AO, unmodified in SMA and reduced in TA
      from ouabain-treated rats. These results suggest that chronic administration of
      ouabain induces hypertension and regional vascular alterations, the latter
      possibly as a consequence of the hypertension.

PMID- 11834626
TI  - Differential effect of FR122047, a selective cyclo-oxygenase-1 inhibitor, in rat
      chronic models of arthritis.
AB  - We investigated the effects of FR122047 (1-[(4,5-bis(4-methoxyphenyl)-2
      thiazoyl)carbonyl]-4-methylpiperazine hydrochloride), a selective cyclo-oxygenase
      (COX)-1 inhibitor, in rat type II collagen-induced arthritis (CIA) and adjuvant
      induced arthritis (AIA). Using an ex vivo rat whole blood assay, FR122047 (0.032 
      3.2 mg kg(-1)) inhibited COX-1-derived thromboxane (TX) B(2) production with
      ED(50) value of 0.059 mg kg(-1), indicating that it was orally active, but did
      not inhibit lipopolysaccharide-induced prostaglandin (PG) E(2) production derived
      by COX-2. Oral administration of FR122047 showed a dose-dependent anti
      inflammatory effect in rat CIA with ED(50) value of 0.56 mg kg(-1). This drug
      also dose dependently suppressed the levels of PGE(2) and TXB(2) in CIA rat paws
      with ED(50) values of 0.24 and 0.13 mg kg(-1), respectively. FR122047 had no
      effect in rat AIA model. In contrast, indomethacin, a non-selective COX
      inhibitor, was anti-inflammatory and reduced the formation of PGs in AIA rat
      paws. Unlike indomethacin, chronic treatment of FR122047 did not damage the
      stomach mucosa in CIA rats. These results demonstrate that COX-1 contributes to
      the oedema and the formation of PGE(2) and TXB(2) in rat CIA model, but not in
      rat AIA model. We conclude that FR122047 has an orally active and anti
      inflammatory effect mediated by inhibition of PGE(2) and TXB(2) produced by COX-1
      at a site of inflammation induced by type II collagen and it may be a useful tool
      for studying the involvement of COX-1 in various in vivo models of inflammation.

PMID- 11834627
TI  - Lysophosphatidylcholine potentiates vascular contractile responses in rat aorta
      via activation of tyrosine kinase.
AB  - We previously reported that while lysophosphatidylcholine (LPC) does not itself
      produce contraction, it significantly potentiates the contractile responses
      induced by high-K(+), UK14,304 (a selective alpha(2)-adrenoceptor agonist) and
      phorbol ester in the endothelium-denuded rat aorta. To further investigate this
      phenomenon, we examined the effects of genistein and tyrphostin B42 (both
      tyrosine kinase inhibitors) on the LPC-induced potentiation of the contractile
      responses to high-K(+) and UK14,304 in the endothelium-denuded rat aorta.
      Although genistein (3 x 10(-6) M, 10(-5) M) did not affect the high-K(+)-induced
      contractile response, it selectively inhibited the potentiating effect of LPC on
      the contraction and it strongly inhibited the LPC-induced augmentation of the
      associated increases in [Ca(2+)](i). Genistein also attenuated the LPC-induced
      augmentation effects on both the increase in [Ca(2+)](i) and contractile response
      induced by the UK14,304. In contrast, daidzein (10(-5) M) did not inhibit the
      potentiating effect of LPC. Tyrphostin B42 (3 x 10(-5) M) attenuated the
      potentiating effect of LPC on high K(+)-induced contractions. Western blot
      analysis showed that LPC increased the tyrosine phosphorylation of a number of
      proteins, including 42 and 44 kDa proteins and 53 - 64 kDa proteins. These
      protein phosphorylations were inhibited by genistein. Sodium orthovanadate (10(
      4) M), a tyrosine phosphatase inhibitor, also markedly enhanced the high-K(+)
      induced contractile responses. This enhancing effect was attenuated by genistein.
      These results suggest that the LPC-induced augmentation of contractile responses
      in the rat aorta is due to activation of tyrosine kinase, which in turn regulates
      Ca(2+) influx.

PMID- 11834628
TI  - Comparison of the ORL1 receptor-mediated inhibition of noradrenaline release in
      human and rat neocortical slices.
AB  - The effects of nociceptin/orphanin (N/OFQ) and the selective ORL1 antagonist J
      113397 (1-[(3R,4R)-1-cyclo-octylmethyl-3-hydroxymethyl-4-piperidyl]-3-ethyl-1,3
      dihydro-2H-benzimidazol-2-one) were studied on electrically-evoked release of
      [(3)H]-noradrenaline ([(3)H]-NA) from human and rat neocortical slices. Specimens
      of human tissue were obtained during neurosurgery. Slices were preincubated with
      0.1 microM [(3)H]-NA, superfused in the presence of desipramine, idazoxan, and
      naloxone (1 microM each), and stimulated electrically up to three times under
      conditions (4 pulses, 100 Hz, 2 ms, 60 mA) that prevent inhibition of evoked
      [(3)H]-NA release by endogenous modulators accumulating during ongoing
      stimulation. N/OFQ decreased electrically-evoked [(3)H]-NA release in both human
      and rat neocortical slices in a concentration-dependent manner. The respective
      pEC(50) values were 7.74 [CI(95): 7.47, 8.04] and 7.64 [CI(95): 7.48, 7.77], and
      the maximal inhibitions were 36.9% [CI(95): 32.4%, 41.8%] and 66.4% [CI(95):
      61.7%, 72.7%]. N/OFQ (1 microM) inhibited K(+) (15 mM)-evoked [(3)H]-NA release
      from neocortical slices of both species by a similar magnitude, either in the
      presence or absence of tetrodotoxin. The nonpeptide ORL1 antagonist J-113397
      competitively attenuated, with similar potency, the inhibition of electrically
      evoked [(3)H]-NA release by N/OFQ in both species (pA(2) values: human, 8.16
      [CI(95): 7.64, 8.64]; rat, 8.47 [CI(95): 8.27, 8.67]). J-113397 (0.1 microM) by
      itself did not alter either the evoked or spontaneous [(3)H]-NA release,
      suggesting that presynaptic ORL1 receptors are not activated by endogenous N/OFQ
      under the stimulation conditions employed. This study provides the first evidence
      that N/OFQ modulates [(3)H]-NA release in human neocortex via specific ORL1
      receptors most likely located on noradrenergic axon terminals.

PMID- 11834629
TI  - Independent contribution of catecholamines to arrhythmogenesis during evolving
      infarction in the isolated rat heart.
AB  - Ventricular fibrillation (VF) in conscious rats with coronary artery ligation
      occurs in two phases, before (phase 1) and after (phase 2) 90 min of ischaemia
      respectively. The mechanisms of phase 2 VF are not established. Interestingly,
      phase 2 VF is absent in isolated (denervated) buffer-perfused rat hearts. We
      investigated whether catecholamine supplementation (to mimic sympathetic drive)
      was sufficient to restore phase 2 VF in such hearts. Isolated rat hearts (n=10
      per group) underwent coronary ligation for 240 min. At 90 min, during a period of
      relative electrical stability, the perfusion solution was switched from standard
      (Krebs) to identical solution or Krebs containing catecholamines (313 nM
      noradrenaline and 75 nM adrenaline) with or without 10 microM trimazosin (an
      alpha(1)-adrenoceptor antagonist) or 10 microM atenolol (a beta(1)-adrenoceptor
      antagonist). Although in all groups the incidence of phase 1 VF was high (80 -
      100%), the temporal distribution of VF was monophasic, i.e. only one heart in one
      group developed phase 2 VF (P=NS). Other ventricular arrhythmias (e.g.,
      tachycardia; VT) exhibited a similar temporal distribution. Nevertheless,
      haemodynamic changes confirmed sympathomimetic effects of catecholamines, e.g.,
      heart rate was increased from 278+/-7 beats min(-1) in controls to 335+/-8 beats
      min(-1) (P<0.05) by catecholamines, an effect that could be blocked by atenolol
      (285+/-7 beats min(-1)) but not by trimazosin (342+/-12 beats min(-1)). Coronary
      flow was correspondingly increased from 7.7+/-0.7 ml min(-1) g(-1) to 16.5+/-1.3
      ml min(-1) g(-1) (P<0.05); this effect could be blocked by atenolol (8.1+/-0.6 ml
      min(-1) g(-1)) and was enhanced by trimazosin (20.7+/-2.4 ml min(-1) g(-1)). In
      conclusion, despite evidence of adequate alpha- and beta-adrenoceptor activation,
      catecholamine supplementation to isolated buffer-perfused rat hearts was
      insufficient to restore phase 2 VF. It therefore appears unlikely that
      catecholamines alone mediate phase 2 VF.

PMID- 11834630
TI  - Aconitine facilitates spontaneous transmitter release at rat ventromedial
      hypothalamic neurons.
AB  - The effects of aconitine, an Aconitum alkaloid, on spontaneous inhibitory and
      excitatory postsynaptic currents (IPSCs and EPSCs respectively) were investigated
      in the mechanically dissociated rat ventromedial hypothalamic (VMH) neurons in
      which native presynaptic nerve terminals remained intact. Under current-clamp
      conditions, aconitine (3 x 10(-6) M) depolarized the neuron with generating the
      action potentials. The aconitine-induced depolarization was markedly suppressed
      in the presence of CNQX but it was facilitated in the presence of bicuculline,
      suggesting that release of excitatory and inhibitory neurotransmitters may be
      involved in the aconitine action in addition to its direct action on postsynaptic
      membrane. Under the voltage-clamp conditions, aconitine reversibly increased the
      frequency of spontaneous IPSC and EPSC frequency, but it did not alter their
      amplitude distribution. Tetrodotoxin (TTX, 3 x 10(-7) M) completely abolished the
      aconitine action on spontaneous IPSC frequency. Likewise removal of extracellular
      Na(+) completely suppressed the aconitine action. Both Ca(2+)-free external
      solution or addition of 10(-4) M Cd(2+) to normal solutions eliminated the
      facilitatory effect of aconitine on the IPSC frequency. Overall these results
      suggest that aconitine depolarizes the presynaptic membrane by activating voltage
      dependent Na(+) channels. Increase of intraterminal Ca(2+) concentration via an
      activation of voltage-dependent Ca(2+) channels in turn enhances the spontaneous
      transmitter release from presynaptic nerve terminals. The presynaptic action of
      aconitine may play a crucial role for membrane excitability of rat VMH neurons.

PMID- 11834632
TI  - Pink puffers vs blue bloaters in asthma too?

PMID- 11834633
TI  - Oropharyngeal dysfunction in COPD patients: the need for clinical research.

PMID- 11834631
TI  - A single subcutaneous bolus of erythropoietin normalizes cerebral blood flow
      autoregulation after subarachnoid haemorrhage in rats.
AB  - Systemic administration of recombinant erythropoietin (EPO) has been demonstrated
      to mediate neuroprotection. This effect of EPO may in part rely on a beneficial
      effect on cerebrovascular dysfunction leading to ischaemic neuronal damage. We
      investigated the in vivo effects of subcutaneously administered recombinant EPO
      on impaired cerebral blood flow (CBF) autoregulation after experimental
      subarachnoid haemorrhage (SAH). Four groups of male Sprague-Dawley rats were
      studied: group A, sham operation plus vehicle; group B, sham operation plus EPO;
      group C, SAH plus vehicle; group D, SAH plus EPO. SAH was induced by injection of
      0.07 ml of autologous blood into the cisterna magna. EPO (400 iu kg(-1) s.c.) or
      vehicle was given immediately after the subarachnoid injection of blood or
      saline. Forty-eight hours after the induction of SAH, CBF autoregulatory function
      was evaluated using the intracarotid (133)Xe method. CBF autoregulation was
      preserved in both sham-operated groups (lower limits of mean arterial blood
      pressure: 91+/-3 and 98+/-3 mmHg in groups A and B, respectively). In the vehicle
      treated SAH-group, autoregulation was abolished and the relationship between CBF
      and blood pressure was best described by a single linear regression line. A
      subcutaneous injection of EPO given immediately after the induction of SAH
      normalized autoregulation of CBF (lower limit in group D: 93+/-4 mmHg, NS
      compared with groups A and B). Early activation of endothelial EPO receptors may
      represent a potential therapeutic strategy in the treatment of cerebrovascular
      perturbations after SAH.

PMID- 11834634
TI  - Waiting to make the weight for lung transplantation.

PMID- 11834635
TI  - Determinants of daytime hypercapnia in obstructive sleep apnea: is obesity the
      only one to blame?

PMID- 11834636
TI  - Noninvasive mechanical ventilation at home: building upon the tradition.

PMID- 11834637
TI  - Monitoring lung mechanics: new applications for established tools.

PMID- 11834638
TI  - Benchmarking in critical care: the road ahead.

PMID- 11834639
TI  - The risk of hospitalization and near-fatal and fatal asthma in relation to the
      perception of dyspnea.
AB  - BACKGROUND: A life-threatening asthma attack is still of major concern. One of
      the main goals in treating patients with asthma is identification of the patients
      at risk of having these attacks. It has been shown that patients who have a near
      fatal asthma attack have a blunted perception of dyspnea (POD). The purpose of
      this study is to measure the POD in patients with asthma, and to relate POD to
      life-threatening attacks within a 24-month follow-up period. METHODS: The POD was
      scored using the Borg scale during breathing against a progressive load at 1-min
      intervals, in order to achieve mouth pressure up to 30 cm H(2)O, in 113
      consecutive asthmatic patients with stable asthma attending an outpatient clinic.
      All patients were invited to regular follow-up every 3 months for up to 24
      months, and all hospitalizations and near-fatal and fatal asthma attacks were
      recorded. The prebronchodilator morning peak expiratory flow rate (PEFR), daily
      regular treatment, and beta(2)-agonist consumption were recorded in a diary card
      for the first 4 weeks. RESULTS: Seventeen patients (15%) had high POD compared to
      the normal subjects, 67 patients (59%) had POD within the normal range, and 29
      patients (26%) had lower-than-normal POD. In the patients with low POD, there was
      a tendency for higher age, higher female/male ratio, and a longer duration of
      disease. The rate of severe asthma was higher in the low-POD group than in the
      normal-POD group, but did not differ from the rate in the high-POD group. The
      mean daily beta(2)-agonist consumption in the patients with low POD was
      significantly lower (p < 0.01) than in the patients with high POD, although the
      mean PEFR was lower in the low-POD group. During the 2 years of follow-up, the
      patients in the low-POD group had statistically significantly more emergency
      department (ED) visits, hospitalizations, near-fatal asthma attacks, and deaths
      compared to the normal-POD and high-POD groups. CONCLUSIONS: Approximately 26% of
      the referral subjects with asthma had low POD when compared to healthy matched
      subjects. Patients with low POD had statistically significantly more ED visits,
      hospitalizations, near-fatal asthma attacks, and deaths during the follow-up
      period. Reduced POD may predispose patients to a life-threatening attack.

PMID- 11834640
TI  - Marginal utility of montelukast for persistent asthma.
AB  - BACKGROUND: The efficacy of a new pharmacologic agent for asthma, in this
      instance the leukotriene receptor antagonist montelukast, is determined in
      controlled trials in research subjects. The utility of a new drug is determined
      by multiple uncontrollable factors in individual patients. OBJECTIVE: To assess
      the utility of montelukast in the management of persistent asthma. DESIGN:
      Observational, retrospective. SETTING: Suburban multispecialty medical clinic.
      METHODS: From April 1998, montelukast was prescribed for 110 patients with
      persistent but controlled asthma, primarily for the corticosteroid-sparing
      effect. Outcomes after 1 year were determined from audits of medical records and
      responses to questionnaires. RESULTS: At least 56% of patients continued
      receiving montelukast for the entire year. However, compared to those patients
      who had discontinued montelukast therapy, those who continued receiving it had no
      difference in the use of inhaled or systemic corticosteroid or inhaled beta(2)
      agonist therapy. CONCLUSION: Montelukast had marginal utility in the management
      of these adult patients with controlled persistent asthma.

PMID- 11834641
TI  - The relationships among hydrogen peroxide in expired breath condensate, airway
      inflammation, and asthma severity.
AB  - STUDY OBJECTIVE: To investigate which cells are the main source of hydrogen
      peroxide (H(2)O(2)) production in stable patients with asthma and the
      associations among H(2)O(2) levels, airway inflammation, and disease severity.
      SETTING: Inpatient respiratory unit and outpatient clinic in tertiary-care
      hospital. PATIENTS: Fifty stable asthmatic patients with disease severity ranging
      from mild to moderate. METHODS: H(2)O(2) was measured in expired breath
      condensate and was correlated with variables expressing both asthma severity (ie,
      FEV(1) percent predicted, peak expiratory flow rate [PEFR] variability, symptom
      score, and histamine airways responsiveness) and airway inflammation (ie,
      differential cell counts from induced sputum and levels of eosinophil cationic
      protein [ECP]). RESULTS: The mean (95% confidence interval [CI]) concentration of
      H(2)O(2) was significantly elevated in patients with asthma compared to that in
      control subjects (mean, 0.67 microM [95% CI, 0.56 to 0.77 microM] vs 0.2 microM
      [95% CI, 0.16 to 0.24 microM]; p < 0.0001). The difference was primarily due to
      the elevation of H(2)O(2) in patients with moderate asthma whose expired breath
      H(2)O(2) level of 0.95 microM (95% CI, 0.76 to 1.12 microM) was significantly
      higher from that of patients with mild-persistent and mild-intermittent asthma
      (mean, 0.59 microM [95% CI, 0.47 to 0.7 microM] and 0.27 [95% CI, 0.23 to 0.32
      microM], respectively; p < 0.0001). H(2)O(2) concentration was positively related
      to sputum eosinophilia as well as to ECP concentration. A similar correlation was
      found between H(2)O(2) and neutrophils in patients with moderate asthma. A
      positive correlation was observed between H(2)O(2) level, symptom score, and PEFR
      variability. H(2)O(2) level was negatively related to FEV(1) percent predicted.
      Further analysis showed that only patients with moderate asthma who were not
      receiving inhaled steroids were found to have a strong relationship with the
      variables tested. CONCLUSIONS: Eosinophils are the predominate cells that
      generate H(2)O(2) in all forms of the disease, while neutrophils might be
      responsible for the highest levels that are observed in the more severe forms of
      the disease. The role of H(2)O(2) concentration in predicting the severity of the
      disease as well as in the inflammatory process is limited and depends on the use
      of inhaled steroid therapy and the classification of the severity of the disease.

PMID- 11834642
TI  - Levels of house dust mite-specific IgE and cockroach-specific IgE and their
      association with lower pulmonary function in Taiwanese children.
AB  - OBJECTIVE: Sensitization to an aeroallergen is known to diminish pulmonary
      function in young children and adults; however, it remains unclear whether it
      produces similar effects in adolescents. This study, therefore, examined the
      relationship between serum allergen-specific IgE levels and pulmonary function in
      adolescents. DESIGN: Middle-school children were invited for a physician's
      evaluation and pulmonary function test when not experiencing an asthma attack and
      for the determination of serum levels of specific IgE to common allergens.
      SETTING: National Cheng Kung University Hospital, Taiwan. SUBJECTS: Middle-school
      children in southern Taiwan, who had completed both a nationally administered
      Chinese version of the International Study of Asthma and Allergies in Childhood
      questionnaire and a pulmonary function test in October 1996. RESULTS: Forty-two
      then currently asthmatic children, 38 children with asthma in remission (no
      reported attack for > 12 months), and 69 children without asthma completed the
      study. Children with asthma had a significantly lower adjusted forced expiratory
      flow between 25% and 75% of FVC (FEF(25-75%)) and FEV(1)/FVC than children
      without asthma. A greater percentage of children with asthma were more sensitized
      to Dermatophagoides pteronyssinus (Der p), Dermatophagoides farinae (Der f), and
      German cockroach but not cat dander or dog dander. Children with asthma with Der
      f-specific IgE > 100 IU/mL, or cockroach-specific IgE > 0.7 IU/mL showed lower
      pulmonary function. No such association was found in children without asthma.
      CONCLUSION: Our findings suggest that sensitization to Der f and German cockroach
      was a critical factor for the lower pulmonary function observed in middle-school
      children with asthma.

PMID- 11834643
TI  - Up-regulation of L-selectin and E-selectin in hypersensitivity pneumonitis.
AB  - BACKGROUND: Selectins are adhesion molecules that contribute to leukocyte
      recruitment into the tissue after an injury. Hypersensitivity pneumonitis (HP) is
      a lymphocytic alveolitis, and we hypothesized that the overexpression of
      selectins could play a role in this process. PATIENTS AND MEASUREMENTS: We
      studied 16 patients with HP and 7 healthy control subjects (HCs). Sera and BAL
      selectins and tumor necrosis factor-alpha were determined by enzyme-linked
      immunosorbent assay, and cellular lung localization was determined by
      immunohistochemistry. Additionally, BAL L-selectin, and L-selectin-bearing T
      lymphocytes analyzed by flow cytometry were evaluated in HP patients and in
      exposed but asymptomatic subjects (EAS). SETTING: Tertiary referral center and
      immunohistochemistry laboratory. RESULTS: Raised levels of E-selectin (mean [+/-
      SD], 178.9 +/- 30.5 vs 59.4 +/- 4.7 ng/mL, respectively; p < 0.001) and P
      selectin (mean, 232.6 +/- 29.9 vs 67.6 +/- 14.2 ng/mL, respectively; p < 0.001)
      were detected in HP patient sera compared to control subjects, while L-selectin
      levels showed no differences between groups. Conversely, HP patients displayed a
      significant increase in levels of L-selectin found in BAL fluid compared with
      both HCs and EAS (11.0 +/- 1.7 vs 6.9 +/- 0.43 and 3.1 +/- 0.5 ng/mL,
      respectively; p < 0.05). The levels of E-selectin found in BAL fluid were similar
      in patients from both groups, and P-selectin was not detected. Percentage of
      CD3+CD62 L+ lymphocytes was lower in HP patients compared with EAS (2.33 +/- 0.8
      vs 4.31 +/- 2.4, respectively; p = 0.05). By immunohistochemistry, L-selectin was
      detected in interstitial macrophages and polymorphonuclear cells, and E-selectin
      was detected in endothelial cells. CONCLUSION: These findings demonstrate that L
      selectin and E-selectin are up-regulated during the development of HP, suggesting
      that they may contribute to the increased traffic of lung inflammatory cells.

PMID- 11834644
TI  - Oropharyngeal deglutition in stable COPD.
AB  - STUDY OBJECTIVES: The aim of this study was to examine deglutition in stable
      patients with COPD and lung hyperinflation. DESIGN: Twenty consecutive, eligible
      COPD patients with an FEV(1) < or = 65% of predicted and a total lung capacity >
      or = 120% of predicted were enrolled prospectively. INTERVENTION: Patients
      received a detailed videofluoroscopic evaluation of oropharyngeal swallowing and
      were compared to 20 age-matched and sex-matched historical control subjects.
      SETTING: An outpatient pulmonary clinic at a Veterans Affairs Medical Center.
      MEASUREMENTS AND RESULTS: The mean total lung capacity, functional residual
      capacity, and residual volume for the patients were 128% of predicted, 168% of
      predicted, and 218% of predicted, respectively. The mean FEV(1) was 39% of
      predicted. There was no evidence of tracheal aspiration in either group. The
      laryngeal position at rest measured relative to the cervical vertebrae was not
      different between groups. The maximal laryngeal elevation during swallowing was
      significantly lower in patients with COPD (p < 0.001). Patients with COPD
      exhibited more frequent use of spontaneous protective swallowing maneuvers such
      as longer duration of airway closure and earlier laryngeal closure relative to
      the cricopharyngeal opening than did control subjects (p < 0.05). CONCLUSIONS: We
      conclude that hyperinflated patients with COPD have an altered swallowing
      physiology. We suspect that the protective alterations in swallowing physiology
      (swallow maneuvers) may reduce the risk of aspiration. However, these swallowing
      maneuvers may not be useful during an exacerbation and may require further
      research.

PMID- 11834645
TI  - Body mass index and the risk of COPD.
AB  - BACKGROUND: Previous studies have documented the prognostic value of low body
      weight in patients with COPD and also in general populations. However, it is not
      clear whether low body weight is a risk factor for COPD or a consequence of
      established disease. STUDY OBJECTIVE: To determine whether asymptomatic subjects
      with low initial body mass were at a greater risk of having COPD develop during
      subsequent follow-up. DESIGN AND SUBJECTS: Observational retrospective study of
      458 male and 192 female participants (age range, 40 to 73 years) in the Baltimore
      Longitudinal Study of Aging. At baseline, the participants did not have COPD.
      After mean follow-up periods of 10.2 years for the men and 6.4 years for the
      women, 40 men and 7 women received a diagnosis of COPD. METHODS: Cox proportional
      hazards regression models were used to assess the relationship between COPD
      diagnosis and baseline body mass index (BMI) in men. RESULTS: The risk of COPD
      developing in men varied inversely with baseline BMI, even after adjusting for
      other risk factors, including cigarette smoking, age, FEV(1) percent predicted,
      abdominal obesity, and educational status. In men, the relative risk of COPD
      developing for the lowest BMI tertile relative to the highest tertile was 2.76
      (95% confidence interval, 1.15 to 6.59). The small number of women who had COPD
      did not allow us to draw conclusions regarding BMI as a risk factor for COPD.
      CONCLUSION: After controlling for confounding variables, men with low BMI are at
      increased risk for getting COPD.

PMID- 11834646
TI  - Discontinuation of furosemide decreases PaCO(2) in patients with COPD.
AB  - STUDY OBJECTIVE: To evaluate whether the discontinuation of furosemide treatment
      resulted in a decrease in PaCO(2) and an increase in daytime and nocturnal
      oxygenation. BACKGROUND: Furosemide is widely prescribed in patients with COPD
      for the treatment of peripheral edema. It is known that furosemide causes a
      metabolic alkalosis. A diminished chemoreceptor stimulation may cause a decreased
      alveolar ventilation. DESIGN: Randomized, double-blind, placebo-controlled,
      crossover trial. SETTING: Department of Pulmonology, Rijnstate Hospital Arnhem,
      the Netherlands. PATIENTS: Twenty patients with stable COPD (10 men; median age,
      70 years [range, 58 to 81 years]; FEV(1) 35% predicted [range, 19 to 70%
      predicted]). Subjects were included if they had received furosemide, 40 mg/d, for
      the treatment of peripheral edema for at least a month and if they had a mean
      nocturnal arterial oxygen saturation (SaO(2)) < 92%. Patients with cardiac left
      and/or right ventricular dysfunction, sleep apneas, and patients receiving other
      diuretics, angiotensin-converting enzyme inhibitors, potassium or chloride
      replacement therapy, or long-term oxygen treatment were excluded. INTERVENTION:
      Furosemide was discontinued for 1 week and replaced by placebo treatment in the
      first or the second week. MEASUREMENTS AND RESULTS: Ventilation, daytime arterial
      blood gas levels, and nocturnal SaO(2) were measured at baseline, after 1, and
      after 2 weeks. Sixteen subjects completed the study. Ventilation increased from
      10.4 L/min (range, 6.7 to 15.4 L/min) at baseline to 11.6 L/min (range, 8.7 to
      14.0 L/min) after discontinuation of furosemide (p < 0.05). PaCO(2) decreased
      from 45 mm Hg (range, 35 to 64 mm Hg) to 41 mm Hg (range, 32 to 61 mm Hg; p <
      0.01). Daytime and nocturnal oxygenation did not improve. CONCLUSIONS: Although
      it does not improve oxygenation, the discontinuation of furosemide decreases
      PaCO(2) in patients with COPD.

PMID- 11834647
TI  - Effects of acetazolamide and furosemide on ventilation and cerebral blood volume
      in normocapnic and hypercapnic patients with COPD.
AB  - STUDY OBJECTIVES: Effects of chronic metabolic alkalosis and acidosis and their
      relation to central chemoregulation may differ between normocapnic and chronic
      hypercapnic patients with COPD. The relationship between responses of inspired
      ventilation (VI), mouth occlusion pressure (P(0.1)), and cerebral blood volume
      (CBV), to short-term changes in arterial PCO(2) was measured. PATIENTS AND
      METHODS: Seventeen patients with chronic hypercapnia and COPD (PaCO(2) > 6.0 kPa)
      and 16 normocapnic patients with COPD (PaCO(2) < or = 6.0 kPa) [FEV(1) 27%
      predicted] were studied under baseline metabolic conditions and after 1 week of
      treatment with oral furosemide, 40 mg/d, or acetazolamide, 500 mg/d. Hypercapnia
      (change in end-tidal carbon dioxide > 1 kPa) was induced by administering
      adequate amounts of carbon dioxide in the inspired air. CBV was measured using
      near-infrared spectroscopy. RESULTS: Compared with baseline metabolic condition,
      chronic metabolic acidosis and alkalosis did not change ventilatory (Delta
      VI/Delta PaCO(2)) and cerebrovascular (Delta CBV/Delta PaCO(2)) reactivity. Base
      excess (BE) decreased by 6.8 +/- 1.1 mEq/L and 6.9 +/- 1.6 mEq/L, respectively,
      in the normocapnic and chronic hypercapnic COPD groups during metabolic acidosis,
      resulting in a not-quite-significant leftward shift of both the ventilatory and
      cerebrovascular carbon dioxide response curve. BE increased by 2.3 +/- 1.2 mEq/L
      and 1.2 +/- 1.3 mEq/L, respectively, during chronic metabolic alkalosis in both
      COPD groups, without concomitant shift. Poor correlations between ventilatory and
      cerebrovascular carbon dioxide responsiveness (Delta CBV/Delta PaCO(2) and Delta
      VI/Delta PaCO(2), Delta CBV/Delta PaCO(2) and Delta P(0.1)/Delta PaCO(2),
      respectively) were found irrespective of baseline, respiratory condition, and
      induced metabolic state. CONCLUSIONS: Normocapnic and chronic hypercapnic COPD
      patients have the same ventilatory and cerebrovascular carbon dioxide
      responsiveness irrespective of induced metabolic state.

PMID- 11834648
TI  - Effect of hyperoxia on gas exchange and lactate kinetics following exercise onset
      in nonhypoxemic COPD patients.
AB  - STUDY OBJECTIVES: The slow oxygen uptake (VO(2)) kinetics observed in COPD
      patients is a manifestation of skeletal muscle dysfunction of multifactorial
      origin. We determined whether oxygen supplementation during exercise makes the
      dynamic VO(2) response faster and reduces transient lactate increase. DESIGN: Ten
      patients with severe COPD (ie, mean [+/- SD] FEV(1), 31 +/- 10% predicted) and 7
      healthy subjects of similar age performed four repetitions of the transition
      between rest and 10 min of moderate-intensity, constant-work rate exercise while
      breathing air or 40% oxygen in random order. Minute ventilation (VE), gas
      exchange, and heart rate (HR) were recorded breath-by-breath, and arterialized
      venous pH, PCO(2), and lactate levels were measured serially. RESULTS: Compared
      to healthy subjects, the time constants (tau) for VO(2), HR, carbon dioxide
      output (VCO(2)), and VE kinetic responses were significantly slower in COPD
      patients than in healthy subjects (70 +/- 8 vs 44 +/- 3 s, 98 +/- 14 vs 44 +/- 8
      s, 86 +/- 8 vs 61 +/- 4 s, and 81 +/- 7 vs 62 +/- 4 s, respectively; p < 0.05).
      Hyperoxia decreased end-exercise E in the COPD group but not the healthy group.
      Hyperoxia did not increase the speed of VO(2) kinetics but significantly slowed
      VCO(2) and E response dynamics in both groups. Only small increases in lactate
      occurred with exercise, and this increase did not correlate with the tau for
      VO(2). CONCLUSION: In nonhypoxemic COPD patients performing moderate exercise,
      the lower ventilatory requirement induced by oxygen supplementation is not
      related to improved muscle function but likely stems from direct chemoreceptor
      inhibition.

PMID- 11834649
TI  - Impact of body weight on long-term survival after lung transplantation.
AB  - STUDY OBJECTIVES: The purpose of this study was to determine the impact of a
      pretransplantation determination of body mass index (BMI) on survival after lung
      transplantation. DESIGN AND PATIENTS: Univariate and multivariate survival
      analyses of a single institution database consisting of 85 patients who had
      undergone lung transplantations between March 1994 and October 1998. SETTING:
      University of Florida Health Science Center. RESULTS: Kaplan-Meier survival
      curves showed that patients who were obese (ie, BMI, > or = 30) at a
      pretransplantation assessment had a marked decrease in posttransplantation
      survival time (log rank, p < 0.05; Wilcoxon, p < 0.05). The final Cox regression
      model revealed that the most powerful predictors of mortality after lung
      transplantation were higher pretransplantation BMI and the development of
      obliterative bronchiolitis. CONCLUSIONS: Our results suggest that the
      posttransplantation risk for mortality is possibly three times greater for obese
      patients than for nonobese patients. Additional study is needed to identify the
      mechanisms for such higher risk in obese patients. Our data also suggest that
      transplantation centers should not routinely reject underweight patients (ie,
      BMI, < 18.5) or overweight patients (ie, BMI, 25 to 29.9) for lung
      transplantation listing solely on the basis of weight, as their outcomes may not
      be significantly different than patients with normal BMIs.

PMID- 11834650
TI  - Prevention of cytomegalovirus infection and disease after lung transplantation:
      results using a unique regimen employing delayed ganciclovir.
AB  - BACKGROUND: Many lung transplant programs employ lengthy regimens of IV
      ganciclovir therapy to prevent disease due to cytomegalovirus (CMV). In 1994, we
      introduced a regimen of delayed ganciclovir prophylaxis for CMV infection. This
      consisted of 2 weeks of IV ganciclovir therapy, initiated 3 to 4 weeks after
      transplantation, with subsequent viral monitoring and preemptive therapy as
      needed. When not receiving ganciclovir, patients received oral acyclovir, 800 mg
      tid, for 6 months. CMV-seronegative patients with seropositive donors also
      received four doses of CMV hyperimmune globulin. This study analyzes the CMV
      outcomes of 54 patients who received the delayed regimen compared to 33
      historical control subjects who received only acyclovir prophylaxis (n = 28) or
      oral acyclovir and 2 to 4 weeks of ganciclovir early after transplantation (n =
      5). METHODS: CMV detection was by shell vial culture or IgG seroconversion; after
      1996, CMV detection was by blood antigenemia. The diagnosis of CMV disease also
      required a typical clinical syndrome or pathologic evidence of CMV. The main
      outcome was the actuarial incidence of CMV infection and disease. In order to
      account for the effect of other important risk factors for CMV infection, the
      time to CMV infection and disease was also studied as dependeant variables in a
      Cox proportional-hazard analysis, with the delayed regimen and other important
      risk factors as independent variables. RESULTS: The delayed regimen reduced the
      actuarial incidence of CMV infection from 80 to 48% (p < 0.001) and CMV disease
      from 31 to 10% (p < 0.01). No seropositive patient receiving the delayed regimen
      developed CMV disease. Twelve of the 54 patients in the study group required
      additional IV antiviral treatment, but the total use of ganciclovir averaged only
      18 days per patient. In a Cox proportional-hazards model, the use of delayed
      ganciclovir was the only factor that showed a significant association with
      freedom from CMV infection (hazard ratio [HR], 0.43; 95% confidence interval
      [CI], 0.24 to 0.75; p = 0.003) and CMV disease (HR, 0.29; 95% CI, 0.10 to 0.86; p
      = 0.03). CONCLUSION: A regimen of CMV prophylaxis employing 2 weeks of IV
      ganciclovir initiated 3 to 4 weeks after lung transplantation followed by
      virologic monitoring and preemptive therapy as needed provides good protection
      against CMV disease.

PMID- 11834651
TI  - Determinants of chronic hypercapnia in Japanese men with obstructive sleep apnea
      syndrome.
AB  - STUDY OBJECTIVE: To identify the determinants of chronic hypercapnia (ie,
      PaCO(2), > or = 45 mm Hg) in men with obstructive sleep apnea syndrome (OSAS)
      without airflow obstruction. DESIGN: An analysis was conducted of 143 male
      patients with OSAS, which had been diagnosed by polysomnography (PSG), who had
      been referred to a university hospital. Patients were classified as hypercapnic
      (ie, PaCO(2), > or = 45 mm Hg) and normocapnic (ie, PaCO(2), < 45 mm Hg), and
      obese (ie, body mass index [BMI], > or = 30 kg/m(2)) or nonobese (ie, BMI, < 30
      kg/m(2)). Patients with airflow obstruction (ie, FEV(1)/FVC ratio, < 70%) were
      excluded from the study. Baseline clinical characteristics, pulmonary function,
      PSG data, and blood gas data were compared between hypercapnic and normocapnic
      patients. Correlations between PaCO(2) and several anthropometric, respiratory,
      and polysomnographic variables were determined by stepwise multiple regression
      analysis. RESULTS: Fifty-five patients (38%) were hypercapnic. Hypercapnic
      patients were younger and heavier, and had more abnormalities on pulmonary and
      PSG testing. Stepwise multiple regression analysis revealed that the PaCO(2)
      level was influenced significantly by the mean level of arterial oxygen
      saturation (SaO(2)) during sleep and by the percent of vital capacity (%VC) (R(2)
      = 0.430; p < 0.0001), indicating that 43% of the total variance in the PaCO(2)
      could be explained by the mean SaO(2) and %VC in hypercapnic patients. In
      contrast, only 13% of the total variance in the PaCO(2) was accounted for by the
      mean SaO(2) and BMI in normocapnic patients (R(2) = 0.134; p = 0.0034). The mean
      SaO(2), %VC, and PaO(2) were selected as independent variables for predicting the
      PaCO(2) in obese patients. These variables explained 41% of the total variance in
      the PaCO(2) (R(2) = 0.407; p < 0.0001), whereas the mean SaO(2) only accounted
      for 13% of the total variance in PaCO(2) levels in nonobese patients (R(2) =
      0.134; p = 0.0064). CONCLUSION: Nocturnal desaturation and restrictive pulmonary
      impairment play major roles in determining the PaCO(2) in hypercapnic and obese
      OSAS patients without airflow obstruction.

PMID- 11834652
TI  - Severe obstructive sleep apnea is associated with left ventricular diastolic
      dysfunction.
AB  - INTRODUCTION: Hypertension is common in patients with obstructive sleep apnea
      (OSA). However, the effect of OSA on ventricular function, especially diastolic
      function, is not clear. Therefore, we have assessed the prevalence of diastolic
      dysfunction in patients with OSA and the relationship between diastolic
      parameters and severity of OSA. METHODS: Sixty-eight consecutive patients with
      OSA confirmed by polysomnography underwent echocardiography. Diastolic function
      of the left ventricle was determined by transmitral valve pulse-wave Doppler
      echocardiography. Various baseline characteristics, severity of OSA, and
      echocardiographic parameters were compared between patients with and without
      diastolic dysfunction. RESULTS: There were 61 male and 7 female patients with a
      mean age of 48.1 +/- 11.1 years, body mass index of 28.5 +/- 4.3 kg/m(2), and
      apnea/hypopnea index (AHI) of 44.3 +/- 23.2/h (mean +/- SD). An abnormal
      relaxation pattern (ARP) in diastole was noted in 25 patients (36.8%). Older age
      (52.7 +/- 8.9 years vs 45.1 +/- 11.3 years, p = 0.005), hypertension (56% vs 20%,
      p = 0.002), and a lower minimum pulse oximetric saturation (SpO(2)) during sleep
      (70.5 +/- 17.9% vs 78.8 +/- 12.9%, respectively; p = 0.049) were more common in
      patients with ARP. By multivariate analysis, minimum SpO(2) < 70% was an
      independent predictor of ARP (odds ratio, 4.34; 95% confidence interval, 1.23 to
      15.25; p = 0.02) irrespective of age and hypertension. Patients with AHI > or =
      40/h had significantly longer isovolumic relaxation times than those with AHI <
      40/h (106 +/- 19 ms vs 93 +/- 17 ms, respectively; p = 0.005). CONCLUSION:
      Diastolic dysfunction with ARP was common in patients with OSA. More severe sleep
      apnea was associated with a higher degree of left ventricular diastolic
      dysfunction in this study.

PMID- 11834653
TI  - Long-term compliance rates to continuous positive airway pressure in obstructive
      sleep apnea: a population-based study.
AB  - STUDY OBJECTIVES: To determine long-term compliance rates to continuous positive
      airway pressure (CPAP) therapy in patients with obstructive sleep apnea enrolled
      in a comprehensive CPAP program in the community. DESIGN: Prospective cohort
      longitudinal study. SETTING: University sleep disorders center. PATIENTS: Two
      hundred ninety-six patients with an apnea-hypopnea index (AHI) > or = 20/h on
      polysomnography. INTERVENTIONS: A CPAP device equipped with a monitoring chip was
      supplied. Within the first week, daily telephone contacts were made. Patients
      were seen at 2 weeks, 4 weeks, 3 months, and 6 months. RESULTS: Of the 296
      subjects enrolled, 81.1% were males. Mean +/- SD AHI was 64.4 +/- 34.2/h of
      sleep; age, 51 +/- 11.7 years; and body mass index, 35.2 +/- 7.9 kg/m(2). The
      mean duration of CPAP use was 5.7 h/d at 2 weeks, 5.7 h/d at 4 weeks, 5.9 h/d at
      3 months, and 5.8 h/d at 6 months. The percentage of patients using CPAP > or =
      3.5 h/d was 89.0% at 2 weeks, 86.6% at 4 weeks, 88.6% at 3 months, and 88.5% at 6
      months. There was a decrease in the Epworth Sleepiness Scale (ESS) score of 44%
      by 2 weeks of therapy. The patients continue to improve over the follow-up
      period, with the lowest mean ESS score observed at 6 months. With multiple
      regression analysis, three variables were found to be significantly correlated
      with increased CPAP use: female gender, increasing age, and reduction in ESS
      score. CONCLUSION: A population-based CPAP program consisting of consistent
      follow-up, "troubleshooting," and regular feedback to both patients and
      physicians can achieve CPAP compliance rates of > 85% over 6 months.

PMID- 11834654
TI  - Spirometry in the supine position improves the detection of diaphragmatic
      weakness in patients with amyotrophic lateral sclerosis.
AB  - STUDY OBJECTIVES: To determine which respiratory function tests best predicted
      diaphragmatic strength in patients with amyotrophic lateral sclerosis. PATIENTS
      AND METHODS: Patients referred for pulmonary evaluation were included (n = 25) if
      they underwent measurement of transdiaphragmatic pressure (Pdi) and one or more
      of the following on the same day: upright FVC, supine FVC, upright FEV(1), supine
      FEV(1), maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP),
      and PaCO(2). Abdominal paradox and use of accessory muscles were also assessed.
      Bivariate analyses were performed using simple linear regression. Sensitivity and
      specificity of the potential predictors to detect an abnormal Pdi (< 70 cm H(2)O)
      were calculated. SETTING: Pulmonary function laboratory of an academic medical
      center. RESULTS: Upright FVC, FEV(1), and MEP were all significantly correlated
      with Pdi, while MIP and PaCO(2) were not. Supine FVC was the most highly
      correlated predictor of Pdi (R(2) = 0.76). A cutoff of supine FVC that was < 75%
      predicted was 100% sensitive and specific for predicting an abnormally low Pdi.
      Accessory muscle use and abdominal paradox were both significantly associated
      with Pdi, and the presence of accessory muscle use had a sensitivity of 84% and a
      specificity of 100% for detecting a low Pdi. CONCLUSIONS: Our findings suggest
      that supine FVC is an excellent and simple test of diaphragmatic weakness.

PMID- 11834655
TI  - Neuroadrenergic denervation of the lung in type I diabetes mellitus complicated
      by autonomic neuropathy.
AB  - STUDY OBJECTIVE: To verify whether autonomic neuropathy (AN) complicating type I,
      insulin-dependent diabetes mellitus affected neuroadrenergic bronchopulmonary
      innervation. PATIENTS: Twenty nonsmoking diabetic patients without respiratory
      diseases were studied: 11 patients with AN (group AN) and 9 patients without AN
      (control; group C) diagnosed by standardized criteria. DESIGN: Patients underwent
      respiratory function tests and ventilatory scintigraphies with (123)I
      metaiodobenzylguanidine (MIBG) and with (99m)Tc-diethylenetriaminepenta-acetic
      acid (DTPA) to assess both bronchopulmonary neuroadrenergic innervation and also
      permeability of the alveolar-capillary barrier to water-soluble tracers. Rates of
      pulmonary clearance of the two tracers were computed, and correlates were
      identified by nonparametric statistics. SETTING: University hospital. RESULTS:
      The AN and C groups had normal respiratory function test results and comparable
      duration of diabetes and quality of metabolic control. (99m)Tc-DTPA clearance did
      not distinguish the groups. (123)I-MIBG clearance was faster in the AN group than
      in the C group (mean +/- SD half-time of the radiotracer time-activity curve
      [T(1/2)], 116.1 +/- 22.8 min in the AN group vs 139.5 +/- 18.3 min in the C
      group, p = 0.022), which is consistent with neuroadrenergic denervation in the AN
      group. (123)I-MIBG clearance was independent from (99m)Tc-DTPA clearance. Faster
      (123)I-MIBG clearance was significantly associated with worse performance in
      three of the four autonomic tests. CONCLUSIONS: Neuroadrenergic bronchopulmonary
      denervation may occur in diabetic patients with AN despite normal clinical and
      respiratory function findings. Further research is needed to identify clinical
      and prognostic implications of these findings.

PMID- 11834656
TI  - Bilateral anterolateral magnetic stimulation of the phrenic nerves can detect
      diaphragmatic fatigue.
AB  - BACKGROUND AND STUDY OBJECTIVES: Measurement of twitch transdiaphragmatic
      pressure (TwPdi) during bilateral phrenic nerve stimulation is presently the best
      method to detect diaphragmatic fatigue in humans. The stimulation methods that
      are currently employed (ie, transcutaneous electrical stimulation [TES] and
      cervical magnetic stimulation [CMS]) have limitations. Bilateral anterolateral
      magnetic stimulation of the phrenic nerves (BAMPS) was recently described. The
      purpose of this study was to determine whether BAMPS can reliably detect
      diaphragmatic fatigue, and to compare the results with BAMPS with those obtained
      with the other stimulation techniques. SUBJECTS: Twelve healthy subjects
      participated in the study. METHODS: TwPdi was measured during TES, CMS, and BAMPS
      before and 10, 30, and 60 min after a potentially fatiguing task. Voluntary
      hyperpnea to task failure was used as the fatiguing task because this task has
      previously been shown to reliably produce contractile fatigue of the diaphragm.
      To determine the reproducibility of BAMPS, TwPdi was measured before and after a
      nonfatiguing task in 10 of the subjects. RESULTS: TwPdi fell significantly after
      the hyperpneic task with all three stimulation techniques, and the amount by
      which TwPdi fell after hyperpnea was not significantly different for the
      different stimulation techniques. The percentage fall in TwPdi after hyperpnea
      was significantly correlated between stimulation techniques (CMS vs BAMPS, r =
      0.72; TES vs BAMPS, r = 0.84; and TES vs CMS, r = 0.67). The mean (+/- SE) within
      subject, between-trial coefficient of variation for TwPdi during BAMPS was 5.1 +/
      0.1%. CONCLUSION: BAMPS is highly reproducible and at least as good at detecting
      diaphragmatic fatigue as the other stimulation techniques.

PMID- 11834657
TI  - Domiciliary-assisted ventilation in patients with myotonic dystrophy.
AB  - STUDY OBJECTIVES: Respiratory failure is found in many neuromuscular diseases,
      even when the lungs may be healthy, because of an inadequacy of the ventilatory
      pump. Long-term domiciliary ventilation is a well-established treatment in
      conditions such as postpoliomyelitis; however, its use in patients with
      respiratory failure secondary to myotonic dystrophy has not been well described.
      The purpose of this study was to review the use of domiciliary-assisted
      ventilation in these patients and to assess their response to treatment. DESIGN:
      Descriptive analysis of retrospective and prospective clinical data. SETTING:
      Inpatient, noninvasive respiratory-care unit in a tertiary referral center.
      PATIENTS: Sixteen patients with myotonic dystrophy, 13 of whom required
      ventilatory support. INTERVENTIONS AND MEASUREMENTS: A retrospective study of all
      patients with myotonic dystrophy referred for assessment for assisted ventilation
      was performed, including results of arterial blood gas analysis, pulmonary
      function tests, and overnight oxygen saturation and transcutaneous carbon dioxide
      levels. A prospective reassessment of all patients established on domiciliary
      ventilation was performed, including measurements of quality of life. RESULTS:
      Results of arterial blood gas analysis showed a fall in mean PaCO(2) from 64.3 to
      53.8 mm Hg (p < 0.05) on discharge after starting ventilation and a rise in mean
      PaO(2) from 53.0 to 65.3 mm Hg (p < 0.05). There were three deaths, at 5 months,
      32 months, and 57 months, respectively. The survivors received assisted
      ventilation for a mean period of 27 months (range, 2 to 76 months). At
      reassessment, improvements in arterial blood gas levels were maintained, with
      mean PaCO(2) of 52.4 mm Hg and PaO(2) of 59.0 mm Hg. Mean overnight mean arterial
      oxygen saturation rose from 80.5 to 90.3% after the start of treatment (p <
      0.001) and was maintained at 90.4% at reassessment. Mean transcutaneous PCO(2)
      during sleep fell from 59.3 to 41.4 mm Hg (p < 0.05), and to 43.7 mm Hg at
      reassessment. There were no significant changes in spirometry or maximum mouth
      pressures. Compliance with treatment for our test group was lower than compliance
      in a group of age- and sex-matched postpoliomyelitis patients. CONCLUSION: Use of
      domiciliary-assisted ventilation in patients with myotonic dystrophy is
      associated with prolonged survival and a sustained improvement in arterial blood
      gas tensions.

PMID- 11834658
TI  - Biochemical and cytologic characteristics of pleural effusions secondary to
      pulmonary embolism.
AB  - STUDY OBJECTIVES: To characterize the biochemical and cytologic constituents of
      pleural effusions secondary to pulmonary embolism. DESIGN: A descriptive clinical
      study. SETTING: A community teaching hospital with 750 beds, which acts as a
      tertiary referral center for several subspecialties. PATIENTS AND INTERVENTIONS:
      Patients with pleural effusions secondary to pulmonary embolism who underwent
      diagnostic thoracentesis during the last 7 years were retrospectively studied.
      Pleural fluid mesothelial hyperplasia was revised and compared with that found in
      patients with pleural effusions of different origin. RESULTS: Pleural effusions
      from all 60 patients with pulmonary embolism were exudates, and in 40 patients
      (67%) contained erythrocyte counts > 10,000/microL. A bloody appearance was not
      related to the use of anticoagulant therapy before thoracentesis.
      Polymorphonuclear leukocytes were predominant in 36 patients (60%); in 11
      patients (18%), a proportion of eosinophils > 10% was found. Mesothelial
      hyperplasia was significantly higher in patients with pulmonary embolism than in
      patients in the control group (p < 0.01). CONCLUSIONS: In the absence of trauma,
      a bloody or eosinophilic effusion with a marked mesothelial hyperplasia should
      prompt a workup to rule out embolism. The finding of transudative pleural fluid
      chemistries in these patients should not be assumed to be secondary to embolism
      before ruling out other causes of transudative effusion.

PMID- 11834659
TI  - Amylase levels in pleural effusions: a consecutive unselected series of 841
      patients.
AB  - STUDY OBJECTIVES: To describe the causes and relative frequency of amylase-rich
      pleural effusion (ARPE), and to study the origin and histologic type of the
      tumors with ARPE, the strength of the association between ARPE and the result of
      pleural cytology, and whether pleural amylase (PA) is a prognostic factor in the
      survival of patients with a malignant pleural effusion. SETTING: Tertiary-care,
      university-affiliated hospital. PATIENTS: Eight hundred forty-one consecutive
      patients with pleural effusion prospectively assessed from 1991 to 1999. RESULTS:
      There were 66 ARPEs: 40 neoplastic, and 26 benign with tuberculosis,
      pancreatitis, and liver cirrhosis as the most frequent causes. Thirty-six percent
      of patients in our series and 61% of patients with ARPE had a neoplastic disease
      (odds ratio [OR], 3; p < 0.001); this association got much stronger for cases
      with PA levels > or = 600 IU/L (95th percentile); [OR, 10; p < 0.001]. The most
      frequent tumor origin was lung cancer (13 cases). Adenocarcinoma was the most
      frequent histologic type (18 cases). Two mesothelioma effusions were ARPEs. There
      was a positive association between ARPE and the finding of tumor cells in pleural
      fluid (OR, 2.79; p < 0.01). In the malignant group, PA levels > or = 600 IU/L
      identified a group of patients with quite a short median survival (p = 0.016).
      CONCLUSIONS: The most common cause of ARPE was neoplasm. There was a positive
      association between ARPE and malignancy, stronger with the highest levels (95th
      percentile). Lung cancer and adenocarcinoma were the most common tumor and
      histologic type associated with ARPE. Mesothelioma may also produce ARPE. There
      was an association between ARPE and the finding of tumor cells in the pleural
      fluid. The highest PA levels identified a group of patients with a median shorter
      survival.

PMID- 11834660
TI  - Effect of continuous positive airway pressure on the rapid shallow breathing
      index in patients following cardiac surgery.
AB  - OBJECTIVES: To compare the rapid shallow breathing index (RSBI) under different
      ventilatory support settings prior to extubation trials. DESIGN: Prospective
      study. SETTING: Cardiac surgery unit at a university hospital. PATIENTS: A total
      of 33 coronary artery bypass grafting patients ready for extubation.
      INTERVENTIONS: Enrolled patients received a continuous positive airway pressure
      (CPAP) trial of 5 cm H(2)O and fraction of inspired oxygen (FIO(2)) of 40%
      (condition 1), a CPAP trial of 5 cmH(2)O and FIO(2) of 21% (condition 2), and a 1
      min spontaneously breathing room air trial without ventilatory support (condition
      3). These trials were applied in random order. MEASUREMENTS AND MAIN RESULTS:
      Average values of respiratory frequency and tidal volume were measured under the
      three experimental conditions in all patients immediately prior to extubation.
      The RSBIs were determined for each patient under each condition; the average
      RSBIs under conditions 1, 2, and 3 were compared for significance. The average
      RSBIs (+/- SD) were significantly smaller under condition 1 (34 +/- 13) and
      condition 2 (36 +/- 14) compared to condition 3 (71 +/- 24). There was no
      significant difference in RSBI between conditions 1 and 2. CONCLUSIONS: The
      administration of 5 cm H(2)O of CPAP can influence the determination of the RSBI.
      In contrast, changes in FIO(2) have no effect on RSBI determination. We speculate
      that using the RSBI during CPAP may mislead the clinician into premature
      discontinuation of mechanical ventilation. Consequently, different threshold
      values for the RSBI should be derived for different ventilatory support levels.

PMID- 11834661
TI  - Cytoreductive surgery and intraoperative hyperthermic intrathoracic chemotherapy
      in patients with malignant pleural mesothelioma or pleural metastases of thymoma.
AB  - STUDY OBJECTIVES: No established curative treatment is available for pleural
      thymoma metastases and malignant pleural mesothelioma (MPM). Recently, peritoneal
      malignancies have been treated by cytoreductive surgery and intraoperative
      hyperthermic intracavitary perfusion chemotherapy (HIPEC). We investigated the
      feasibility and safety of this multimodality treatment in the thoracic cavity.
      DESIGN: Patients with pleural thymoma metastases or early-stage MPM were enrolled
      in a feasibility study. Morbidity, recurrence, and survival rates were recorded.
      SETTING: The Netherlands Cancer Institute. PATIENTS: Three patients with pleural
      thymoma metastases and 11 patients with pleural mesothelioma were treated.
      INTERVENTIONS: Cytoreductive surgery and intraoperative hyperthermic
      intrathoracic perfusion chemotherapy (HITHOC) with cisplatin and adriamycin were
      performed. The mesothelioma patients received adjuvant radiotherapy on the
      thoracotomy wound and drainage tracts. MEASUREMENTS AND RESULTS: Morbidity and
      mortality rates were 47% and 0%, respectively. Reoperation was necessary in four
      cases. Severe chemotherapy-related complications were not observed. A solitary
      mediastinal and a contralateral pleural thymoma recurrence were successfully
      treated by radiotherapy and a contralateral HITHOC procedure. All thymoma
      patients were alive and free of disease after a mean follow-up period of 18
      months. After a mean follow-up period of 7.4 months, nine mesothelioma patients
      are alive. Two mesothelioma patients died of contralateral pleural and peritoneal
      recurrent disease, while one patient is alive with locoregional recurrence.
      CONCLUSIONS: Cytoreductive surgery and HITHOC with cisplatin and adriamycin is
      feasible in patients with pleural thymoma metastases and early-stage MPM, and is
      associated with acceptable morbidity rates. Early data on locoregional disease
      control are encouraging, and a phase II study will be conducted.

PMID- 11834662
TI  - Discharge criteria from perioperative physical therapy.
AB  - OBJECTIVES: To develop valid and reliable hospital discharge criteria and a
      scoring system that would be used to assess when a patient should be discharged
      from perioperative physical therapy (PT) care. DESIGN: We developed the
      postoperative physiotherapy discharge scoring tool (POP-DST), a tool composed of
      objective criteria and a scoring system that would be used to determine when a
      patient should be discharged from perioperative PT. It is a composite score of
      the following five subcategories: mobility; breath sounds; secretion clearance;
      oxygen saturation; and respiratory rate. The score for the POP-DST ranges from 6
      to 15, with a score of > 13 indicating readiness for discharge. We examined the
      content validity of the the POP-DST using focus groups and a mailed survey. To
      determine interrater reliability, two therapists, who were blinded to each
      other's scores, assessed postsurgical patients. Validity was examined by
      comparing the decision to discharge based on the score on the POP-DST to the
      decision to discharge according to the therapist's judgment. In addition,
      subjects who were discharged from PT were followed-up 7 to 10 days later to
      determine whether they had developed any subsequent respiratory problems.
      PATIENTS: One hundred four surgical patients were assessed to determine the
      reliability and validity of the POP-DST. For the ability of the test to detect
      postoperative complications following discharge from PT, 204 surgical patients
      were followed-up after discharge from PT. RESULTS: Interrater reliability was
      moderately high (intraclass correlation coefficient = 0.76; r = 0.77). There was
      strong agreement between the decision to discharge the patient from PT based on
      the tool criteria compared to the therapist's judgment (kappa range, 0.91 to
      0.96). The ability of the POP-DST to predict those patients who would not develop
      complications postoperatively was 94%. CONCLUSION: The results indicate that the
      POP-DST would facilitate clinical decision making related to PT discharge
      planning in postsurgical populations. The instrument demonstrated strong content
      validity and predictive validity, as well as high levels of interobserver
      agreement. This tool should be considered as a work in progress until it is more
      fully validated.

PMID- 11834663
TI  - Role of biochemical tests in the diagnosis of large pericardial effusions.
AB  - STUDY OBJECTIVES: To determine the biochemical characteristics of large
      pericardial effusions in various disease states, and to assess their utility as
      diagnostic tools. SETTING: An academic university hospital in the Western Cape,
      South Africa. DESIGN: Consecutive, prospective case series. PATIENTS: One hundred
      ten hospital patients > 12 years old, who presented to the echocardiography
      department with large pericardial effusions, and 12 control subjects who
      underwent open-heart surgery (coronary artery bypass graft or aortic valve
      replacement). MEASUREMENTS: Fluid was sent for examination of biochemistry,
      adenosine deaminase, microbiology, hematology, and cytology. The etiology of each
      pericardial fluid sample was established using predetermined criteria. RESULTS:
      The biochemistry of pericardial exudates differed significantly from pericardial
      transudates. Light' s criteria (whereby an exudate is defined as having one or
      more of the following: pleural fluid/serum protein ratio > 0.5; pleural
      fluid/serum lactate dehydrogenase [LDH] ratio > 0.6; and/or pleural fluid LDH
      level > 200 U/L) were applied to pericardial fluids and demonstrated to be the
      most reliable diagnostic tool for identifying pericardial exudates. The
      corresponding sensitivity was 98%. CONCLUSION: Although laboratory tests are a
      useful guideline when assessing the etiology and pathophysiology of pericardial
      effusions, the majority of large, clinically significant pericardial effusions
      result from exudative causes.

PMID- 11834664
TI  - Aortic spontaneous echocardiographic contrast and hemostatic markers in patients
      with nonrheumatic atrial fibrillation.
AB  - OBJECTIVES: To determine the relationship between spontaneous echocardiographic
      contrast (SEC) in the descending thoracic aorta and plasma levels of hemostatic
      markers in patients with nonrheumatic atrial fibrillation (AF). DESIGN AND
      SETTINGS: A cross-sectional study at a university hospital. PATIENTS AND
      MEASUREMENTS: In 91 consecutive patients (mean +/- SE age, 70 +/- 1 years; 68
      men) with nonrheumatic AF who underwent transesophageal echocardiography, plasma
      levels of markers for platelet activity (platelet factor 4 [PF4] and beta
      thromboglobulin [beta-TG]), thrombotic status (thrombin-antithrombin III complex
      [TAT]), and fibrinolytic status (D-dimer and plasmin-alpha(2)-plasmin inhibitor
      complex [PIC]) were determined. RESULTS: Forty-three patients who had aortic SEC
      (AoSEC) were older (72 years vs 68 years; p < 0.05) and had a higher prevalence
      of chronic AF (88% vs 52%; p < 0.05) than 48 patients without AoSEC. TAT, PIC,
      and D-dimer levels were significantly higher in patients with AoSEC than in those
      without AoSEC, whereas PF4 and beta-TG levels were not different between the two
      groups. Although the prevalence of cerebral embolism did not differ between the
      two groups (23% vs 29%), the prevalence of peripheral embolism was higher in
      patients with AoSEC than in those without AoSEC (10% vs 0%; p < 0.05).
      Multivariate analysis revealed mitral regurgitation (odds ratio, 7.53; p < 0.02),
      SEC in the left atrium (odds ratio, 2.14; p < 0.02), and aortic atherosclerosis
      (odds ratio, 1.87; p < 0.04) emerged as independent predictors of AoSEC.
      CONCLUSIONS: Patients with nonrheumatic AF who have AoSEC appear to have enhanced
      coagulation activity but not platelet activity. Intensive anticoagulation
      treatment might be required for these patients.

PMID- 11834665
TI  - Left ventricular remodeling, systolic function, and diastolic function in young
      adults with beta-thalassemia intermedia: a Doppler echocardiography study.
AB  - BACKGROUND: The aim of this study was to investigate the left ventricular (LV)
      remodeling and function in 24 asymptomatic young adults affected by beta
      thalassemia intermedia (TI), in order to compare the obtained data with that of
      80 patients affected by beta-thalassemia major (TM) and 65 healthy subjects.
      METHODS: LV volumes and shapes, mass index, mass/volume ratio, systolic and
      diastolic function, stroke volume, and cardiac index were determined by two
      dimensional and M-mode echocardiography. RESULTS: In the TM and TI groups, LV
      volumes, diastolic and systolic shapes were significantly different from the
      control subjects, but the ejection fraction was slightly reduced only in the TM
      group. The TI group had larger LV volumes than did the TM group (mean [+/- SD]
      end-diastolic volume index, 99.4 +/- 21.9 vs 82.7 +/- 21.5 mL/m(2), respectively
      [p < 0.005]; mean end-systolic volume index, 42.8 +/- 12.2 vs 36.1 +/- 12.9
      mL/m(2), respectively [p < 0.05]). Both groups showed an increase of the LV mass
      index, but the mass/volume ratio did not differ from the control subjects. The
      systolic volume index and the cardiac index were increased in both groups, but
      the increase was more pronounced in the TI group. Fractional shortening (FS) and
      the mean velocity of circumferential shortening (mVCFc) were decreased in the TM
      group (FS, 33.6 +/- 5.5% vs 36.9 +/- 4.1, respectively [p < 0.001]; mVCFc, 1.06
      +/- 0.18 vs 1.17 +/- 0.12 circumference per second, respectively [p < 0.0001]).
      The LV contractile state was depressed only in the TM group, and the preload
      index was normal in both. LV filling showed an increase in the total flow
      velocity integral due to increases in the peak E wave (E) and peak A wave (A)
      velocities and integrals, with an increase of the E/A ratio in the TM group and a
      slight decrease in the TI group. The isovolumic relaxation time was prolonged in
      both groups. There was no major derangement in the pulmonary venous flow.
      CONCLUSIONS: Asymptomatic young adults with TI show significant increases in LV
      volumes, LV mass, and cardiac index that are more pronounced than those in TM
      patients. LV systolic function is preserved in the TI group but is slightly
      depressed in the TM group due to the increase of afterload and to reduced
      contractility. The hemodynamic and hematologic factors involved in the
      etiopathogenesis of these findings are discussed, such as the treatment strategy.

PMID- 11834666
TI  - The prognostic role of the ECG in primary pulmonary hypertension.
AB  - BACKGROUND/RATIONALE: Doppler echocardiography and invasive hemodynamic
      parameters reflective of right ventricular failure are associated with a poor
      prognosis in patients with primary pulmonary hypertension (PPH). The aims of the
      present study were to examine whether ECG features in patients with PPH are
      associated with a decrease in survival, and to determine the value of the ECG in
      risk stratification. METHODS/RESULTS: We analyzed the ECG, New York Heart
      Association (NYHA) class, and hemodynamic parameters in 51 untreated patients
      with PPH (88% women; mean age, 41.7 years; 79% NYHA classes III and IV) evaluated
      between 1992 and 1998. Subsequent treatment included epoprostenol in 37 patients,
      calcium channel blockers in 10 patients, epoprostenol and atrial septostomy in 2
      patients, and lung transplant in 3 patients. As of 1999, 16 patients had died.
      Based on Kaplan-Meier estimates, median survival was > 6.5 years and estimated
      survival at 1 year, 3 years, and 5 years was 86%, 71%, and 57%, respectively.
      Significant predictors of decreased survival by Cox regression analysis include
      pulmonary vascular resistance (PVR; hazard ratio [HR], 1.11 per Wood unit),
      cardiac index (HR, 0.22 per L/min/m(2)), p wave amplitude in lead II (HR, 3.06
      per mm), p > or = 0.25 mV in lead II (HR, 2.77), qR in V(1) (HR, 3.55), and World
      Health Organization criteria for right ventricular hypertrophy (HR, 4.26). After
      controlling for PVR, the HRs attributable to the ECG criteria were only slightly
      diminished. NYHA class and pulmonary artery pressures did not correlate with a
      decrease in survival. CONCLUSIONS: ECG parameters reflective of physiologic and
      anatomic abnormalities in the right ventricle are associated with decreased
      survival in patients with PPH, and may be useful for deciding therapeutic choices
      including the timing for lung transplantation listing.

PMID- 11834668
TI  - Role of fine-needle aspirates of focal lung lesions in patients with hematologic
      malignancies.
AB  - OBJECTIVES: To evaluate the yield and safety of transthoracic fine-needle
      aspiration (FNA) in the diagnosis of pulmonary disease in patients with
      hematologic malignancy. DESIGN: Retrospective chart review. SETTING: Tertiary
      care medical center. PATIENTS: Sixty-seven patients with a hematologic malignancy
      or after bone marrow transplantation (BMT) for a hematologic malignancy who
      underwent a total of 71 FNAs for diagnosis of an unexplained parenchymal lung
      lesion from January 1, 1991, to June 30, 1999. RESULTS: The underlying malignancy
      was lymphoma in 42 patients (63%), leukemia in 8 patients (12%), after allogeneic
      BMT in 12 patients (18%), after autologous BMT in 3 patients (4%), and other
      diseases in 2 patients. Radiographs showed focal abnormalities in all cases, and
      were nodules in 37%, masses in 37%, focal infiltrates in 21%, and cavitary
      lesions in 5%. The yield of FNA for a finding specific infection or cancer was
      56% (40 of 71 FNAs). The FNA with inflammatory changes was clinically sufficient
      in another 11 patients for a total yield of 72% (51 of 71 FNAs). The yield for
      lung cancer was 90% (9 of 10 FNAs), for pulmonary lymphoma was 68% (21 of 31
      FNAs), and for infection was 67% (10 of 15 FNAs). Complications occurred in 18 of
      71 FNAs (25%), with pneumothorax in 14 patients (20%) and chest tube placement
      required in 4 patients (6%). Bleeding occurred in six patients (8%), including
      one death in a patient with abnormal hematologic parameters. CONCLUSION:
      Transthoracic FNA in patients with hematologic malignancy and focal lung lesions
      has an excellent yield for detecting cancer and a yield comparable to
      bronchoscopy for the diagnosis of infections. It should be considered a useful
      diagnostic tool in this setting.

PMID- 11834667
TI  - Elevated levels of alpha-defensins in plasma and BAL fluid of patients with
      active pulmonary tuberculosis.
AB  - STUDY OBJECTIVES: To investigate the role of neutrophil peptides named alpha
      defensins in patients with pulmonary tuberculosis (TB). PATIENTS: Thirty-seven
      patients with TB and 25 healthy subjects. MEASUREMENTS AND RESULTS:
      Concentrations of alpha-defensins (human neutrophil peptide [HNP]-1, HNP-2, and
      HNP-3) were measured by radioimmunoassay in plasma and BAL fluid (BALF).
      Concentrations of alpha-defensins were significantly higher in plasma and BALF of
      patients with TB than in healthy subjects. In BALF of patients with TB, the
      concentration of alpha-defensins correlated positively with the levels of
      interleukin 8, and higher concentrations of alpha-defensins in BALF were also
      detected in patients with cavitary lesions. There was an inverse relationship
      between plasma alpha-defensins and FEV(1)/FVC ratio before treatment, and between
      plasma concentrations of alpha-defensins before treatment and the improvement in
      percentage of vital capacity after treatment. Plasma alpha-defensin
      concentrations returned to the normal range after treatment. CONCLUSION: Our data
      suggest that alpha-defensins released from neutrophils may play an important role
      in the pathogenesis of TB, and that plasma alpha-defensin concentration may be a
      useful marker of disease severity and deterioration of pulmonary function.

PMID- 11834669
TI  - Central venous and bladder pressure reflect transdiaphragmatic pressure during
      pressure support ventilation.
AB  - STUDY OBJECTIVES: To determine whether the change in bladder pressure (Pblad) and
      central venous pressure (Pcvp) may reflect the changes in esophageal pressure
      (Pes) and gastric pressure (Pgas) when inspiratory pressure support (IPS) is
      altered. DESIGN: Prospective clinical study. SETTING: The ICUs of a teaching
      hospital. PATIENTS: Ten patients currently receiving IPS ventilation via a
      tracheostomy or an endotracheal tube who already had bladder and central venous
      catheters in situ. MEASUREMENTS AND RESULTS: Airway pressure, Pes, Pgas, Pcvp,
      Pblad, and flow were measured at the original IPS setting. IPS then was reduced
      by 5-cm H(2)O increments until IPS was zero or was at the minimum pressure that
      could be tolerated by each patient. At each level of IPS, pressures and flow were
      measured at steady-state breathing. The maximum pressure difference for each
      pressure during inspiration was calculated. We found that the Delta Pblad
      correlated closely with the Delta Pgas (r = 0.904) and that the Delta Pes
      correlated with the Delta Pcvp (r = 0.951). When the Delta Pcvp - Delta Pblad was
      compared with the transdiaphragmatic pressure for each patient as the IPS was
      altered, the correlation coefficients varied from 0.952 to 0.999. CONCLUSION:
      Although absolute values for the Delta Pcvp during mechanical ventilation do not
      always reflect the Delta Pes, useful information can be obtained from this route.
      In individual patients, the two sites of measurement followed each other when IPS
      was changed, enabling a bedside assessment of the response to reducing
      respiratory support.

PMID- 11834670
TI  - A cross-cultural comparison of critical care delivery: Japan and the United
      States.
AB  - OBJECTIVE: To compare the utilization and outcomes of critical care services in a
      cohort of hospitals in the United States and Japan. DESIGN: Prospective data
      collection on 5,107 patients and detailed organizational characteristics from
      each of the participating Japanese study hospitals between 1993 and 1995, with
      comparisons made to prospectively collected data on the 17,440 patients included
      in the US APACHE (acute physiology and chronic health evaluation) III database.
      SETTING: Twenty-two Japanese and 40 US hospitals. PATIENTS: Consecutive,
      unselected patients from medical, surgical, and mixed medical/surgical ICUs.
      MEASUREMENTS: Severity of illness, predicted risk of in-hospital death, and ICU
      and hospital length of stay (LOS) were assessed using APACHE III. Japanese ICU
      directors completed a detailed survey describing their units. MAIN RESULTS: US
      and Japanese ICUs have a similar array of modalities available for care. Only
      1.0% (range, 0.56 to 2.7%) of beds in Japanese hospitals were designated as ICUs.
      The organization of the Japanese and US ICUs varied by hospital, but Japanese
      ICUs were more likely to be organized to care for heterogeneous diagnostic
      populations. Sample case-mix differences reflect different disease prevalence.
      ICU utilization for women is significantly lower (35.5% vs 44.8% of patients) and
      there were relatively fewer patients > or = 85 years old in the Japanese ICU
      cohort (1.2% vs 4.6%), despite a higher per capita rate of individuals > or = 85
      years old in Japan. The utilization of ICUs for patients at low risk of death
      significantly less in Japan (10.2%) than in the United States (12.9%). The APACHE
      III score stratified patient risk. Overall mortality was similar in both national
      samples after accounting for differences in hospital LOS, utilizing a model that
      was highly discriminating (receiver operating characteristic, 0.87) when applied
      to the Japanese sample. The application of a US-based mortality model to a
      Japanese sample overestimated mortality across all but the highest (> 90%)
      deciles of risk. Significant variation in expected performance was noted between
      hospitals. Risk-adjusted ICU LOS was not significantly longer in Japan; however,
      total hospital stay was nearly twice that found in the US hospitals, reflecting
      differences in hospital utilization philosophies. CONCLUSIONS: Similar high
      technology critical care is available in both countries. Variations in ICU
      utilization reflect differences in case-mix and bed availability. Japanese ICU
      utilization by gender reflects differences in disease prevalence, whereas
      differences in utilization by age may reflect differences in cultural norms
      regarding the limits of care. Such differences provide context from which to
      assess the delivery of care across international borders. Miscalibration of
      predictive models applied to international data samples highlight the impact that
      differences in resource use and local practice cultures have on outcomes. Models
      may require modification in order to account for these differences. Nevertheless,
      with large databases, it is possible to assess critical care delivery systems
      between countries accounting for differences in case-mix, severity of illness,
      and cultural normative standards facilitating the design and management such
      systems.

PMID- 11834671
TI  - 2-month mortality and functional status of critically ill adult patients
      receiving prolonged mechanical ventilation.
AB  - STUDY OBJECTIVES: To describe the 2-month mortality and functional status of
      adult patients receiving prolonged (at least 48 h) mechanical ventilation (MV),
      and to identify patient characteristics that are associated with 2-month
      mortality. DESIGN: Prospective cohort study. SETTING: Four ICUs at a tertiary
      care institution. PATIENTS: Eight hundred seventeen patients who received
      prolonged MV. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Median age, sex
      distribution, and median Charlson comorbidity score of the 817 patients were 65
      years, 45.8% women, and 1, respectively. The median scores on Katz Activities of
      Daily Living, Instrumental Activities of Daily Living Deficits, and Medical
      Outcomes Study Short-Form 36 surveys before hospitalization were 0, 1, and 50,
      respectively. Median APACHE (acute physiology and chronic health evaluation) III
      score and probability of hospital death for the cohort were 64 and 0.31,
      respectively. Median duration of MV was 9 days. Two-month mortality was 43%.
      Independent predictors of mortality at 2 months were age, comorbidities, and
      prehospital functional status. The adjusted odds of dying within 2 months
      increased 34% for each decade increase in age. Functional status deteriorated at
      2 months compared to functional status prior to hospitalization, and 35% of the
      survivors were at risk for clinical depression. Among the 2-month survivors for
      whom the need for a caregiver was assessed, 78% had a caregiver. CONCLUSIONS:
      Older age, in addition to functional status and comorbidities, was associated
      with increased mortality at 2 months. Functional status of survivors declined at
      2 months.

PMID- 11834672
TI  - Comparison of cardiac output and circulatory blood volumes by transpulmonary
      thermo-dye dilution and transcutaneous indocyanine green measurement in
      critically ill patients.
AB  - OBJECTIVE: We prospectively studied the agreement between transpulmonary aortic
      fiberoptic-based and pulse dye densitometry (PDD) measurements of cardiac output
      and circulatory blood volumes. DESIGN: Prospective clinical study. SETTING:
      Operative ICU of a university hospital. PATIENTS: Sixteen critically ill, deeply
      sedated patients receiving mechanical ventilation with ARDS (n = 8),
      sepsis/septic shock (n = 6), subarachnoid hemorrhage (n = 1), and severe head
      injury (n = 1). MEASUREMENTS AND RESULTS: Each patient received a 4F aortic
      catheter with an integrated fiberoptic and thermistor that was connected to a
      computer system for automatic calculation of the transpulmonary indicator
      dilution (TPID) technique for the measurement of cardiac output (COTPID),
      intrathoracic blood volume (ITBV), and total blood volume measured by TPID
      technique (TBVTPID). In each patient, an indocyanine green sensor was attached to
      one nasal wing and connected to an analyzer for the PDD measurement of cardiac
      output (COPDD), central blood volume (CBV), and TBV measured by PDD (TBVPDD). For
      all first measurements, linear regression analysis between COTPID and COPDD
      revealed that COPDD = 0.63 x COTPID + 3.69 (L/min) [r = 0.64, p = 0.008]. Mean
      bias between both techniques was - 0.8 L/min (SD, 1.7 L/min). Correlations
      between ITBV/CBV (r = 0.52) and TBVTPID/TBVPDD were only moderate: TBVPDD = 0.74
      x TBVTPID + 2,362 (mL) [r = 0.60, p = 0.015; mean bias, - 999 mL; SD, 1,353 mL].
      Over all 55 measurements, TPID measurements were on average 11.5% (cardiac
      output) and 17.6% (TBV) higher than PDD measurements. The differences between
      both measurements ranged from - 58 to 81% (cardiac output) and from - 47 to 82%
      (TBV; 95% reference ranges). The main source of variation were the
      intraindividual differences, resulting in different peaks and trends in the
      patients time courses depending on which measurement method was used. CONCLUSION:
      PDD measurement of cardiac output and circulatory blood volumes agrees moderately
      with transpulmonary thermo-dye dilution technique in critically ill patients.

PMID- 11834673
TI  - Effects of partial liquid ventilation on unilateral lung injury in dogs.
AB  - STUDY OBJECTIVE: The overall physiologic effect of partial liquid ventilation
      (PLV) in the setting of unilateral lung injury remains unclear. Therefore, we
      evaluated the effect of PLV on gas exchange in unilateral lung injury. DESIGN AND
      METHODS: Left unilateral lung injury was induced in 14 adult dogs by oleic acid
      instillation into a left pulmonary artery. The animals were divided into two
      groups: gas ventilation (GV) and PLV. During both GV and PLV, systemic blood gas
      levels were analyzed. Oxygen consumption (O(2)), carbon dioxide production
      (CO(2)) and pulmonary blood flow (Q) of both the right lung (uninjured lung) and
      left lung (injured lung) were measured. RESULTS: During PLV, O(2) of the injured
      left lung (o(2)-injured), CO(2) of the injured left lung (CO(2)-injured), and Q
      of the injured left lung (Q-injured) were greater than those in GV (O(2)-injured,
      41.6 mL/min vs 23.4 mL/min, p = 0.006; CO(2)-injured, 34.4 mL/min vs 25.5 mL/min,
      p = 0.026; and Q-injured, 0.47 L/min vs 0.22 L/min, p = 0.002, respectively).
      However, overall PaO(2) during PLV was less than that during GV, likely due to
      either a redistribution of Q toward the injured lung (PLV Q-injured, 0.47 L/min
      vs GV Q-injured, 0.22 L/min; p = 0.002) or reduced gas exchange efficiency in the
      healthy lung. CONCLUSIONS: We conclude that in our model, PLV increases O(2) and
      VCO(2) in the injured lung. However, over all gas exchange efficiency is reduced.

PMID- 11834674
TI  - Tissue lipid peroxidation and reduced glutathione depletion in hypochlorite
      induced lung injury.
AB  - STUDY OBJECTIVE: Neutrophils are involved in acute lung injury during ARDS via
      several mechanisms. This study focuses on neutrophil-derived oxidative stress.
      Hypochlorite is a major neutrophil-derived oxidant. This study characterizes
      hypochlorite-induced acute changes in pulmonary circulation and the involvement
      of tissue lipid peroxidation (LPO) and reduced glutathione (rGSH) depletion.
      METHODS: Hypochlorite (500, 1,000, and 2,000 nmol/min) or buffer (control) were
      infused into isolated rabbit lungs. Pulmonary artery pressure (PAP), capillary
      filtration coefficient (Kf,c) [10(4)/mL/s/cm H(2)O/g], and lung weight were
      measured. Experiments were terminated after 105 min or when fluid retention was >
      50 g. Lung tissue was frozen immediately after termination of the experiments and
      analyzed for LPO products and rGSH (nanomoles per milligram of protein). RESULTS:
      Baseline PAP and Kf,c values averaged from 6.1 to 6.5 mm Hg and from 0.97 to
      1.23, respectively, in all groups. Hypochlorite infusion of 500, 1,000, and 2,000
      nmol/min (n = 5 to 7 per group) evoked an increase (mean +/- SEM) in maximum PAP
      (PAPmax) [12.9 +/- 2.1, 14.3 +/- 1.7, and 13.3 +/- 2.2 mm Hg], in maximum Kf,c
      (Kf,cmax) [1.9 +/- 1.2, 6.34 +/- 1.2, and >10.0], and in tissue LPO products (1.7
      +/- 0.06, 2.1 +/- 0.06, and 2.3 +/- 0.11 vs 1.4 +/- 0.04 in controls), and a
      decrease in tissue rGSH (73.4 +/- 8.7, 43.0 +/- 9.6, and 50.4 +/- 7.2 vs 139 +/-
      12.6 in controls). Parameters of lung injury (PAPmax and Kf,cmax) of each single
      experiment were closely correlated with tissue rGSH but did not correlate with
      tissue LPO products. All changes are significant (p < 0.05) vs control.
      CONCLUSION: The neutrophil-specific oxidant hypochlorite induces acute lung
      injury, rGSH depletion, and LPO in isolated rabbit lungs. The lung injury
      correlates with rGSH depletion, suggesting an important mechanistic role in
      hypochlorite-induced acute lung injury.

PMID- 11834675
TI  - Inhibition of human neutrophil elastase-induced acute lung injury in hamsters by
      recombinant human pre-elafin (trappin-2).
AB  - STUDY OBJECTIVES: Pre-elafin, also known as trappin-2, is an elastase-specific
      inhibitor that could be an ideal candidate for the treatment of neutrophil
      elastase-driven lung diseases. The inhibitory activity of pre-elafin resides in
      the COOH-terminal region that can be released as mature elafin. The NH(2)
      terminal moiety of pre-elafin is characterized by the presence of a specific
      repeating sequence, termed cementoin, believed to immobilize the inhibitor to
      lung protein components and restrict its diffusion from the desired sites of
      action. This property should confer an advantage to pre-elafin compared to elafin
      in the treatment of neutrophil elastase-driven lung diseases. MEASUREMENTS: The
      inhibitory effect of recombinant human pre-elafin was assessed in a human
      neutrophil elastase-induced acute lung injury model in Golden Syrian hamsters.
      BAL fluid hemoglobin content was used as a marker of lung injury. RESULTS:
      Recombinant human pre-elafin administered intratracheally 1 h prior to neutrophil
      elastase dose-dependently inhibited the lung hemorrhage with a calculated half
      effective dose of 8.1 microg/kg (0.7 nmol/kg). Pre-elafin was equally efficient
      when administered 3 h before neutrophil elastase. In contrast to pre-elafin,
      commercial synthetic elafin was ineffective in inhibiting neutrophil elastase
      induced lung hemorrhage even at a dose of 4.45 nmol/kg. CONCLUSIONS: Our results
      suggest that pre-elafin may be eventually used in the treatment of neutrophil
      elastase-driven lung diseases.

PMID- 11834676
TI  - Changes in (Na + K)-adenosine triphosphatase activity and ultrastructure of lung
      and kidney associated with oxidative stress induced by acute ethanol
      intoxication.
AB  - STUDY AND OBJECTIVES: (Na + K)-adenosine triphosphatase (ATPase) activity,
      oxidative stress parameters, and morphologic characteristics of the lung and
      kidney of rats under acute ethanol intoxication were assessed to investigate the
      pathogenic mechanism of tissue damage. DESIGN AND INTERVENTIONS: Adult rats were
      given ethanol (5.5 g/kg) 3 h before performing the biochemical and morphologic
      studies. Oxidative stress was assessed by measuring the levels of reduced
      glutathione (GSH) and glutathione disulfide (GSSG), the activities of key
      antioxidant enzymes (ie, catalase [CAT], superoxide dismutase [SOD], and
      glutathione peroxidase [GSH-Px]) and malondialdehyde production. (Na + K)-ATPase,
      a membrane-bound enzyme, also was assayed. RESULTS: In the lung, ethanol
      increased MDA production by 60%, decreased GSH levels by 33%, decreased SOD and
      GSH-Px activity by 10%, and decreased (Na + K)-ATPase activity by 55%, whereas
      CAT activity was unaltered. Impaired surfactant secretion and cell adhesion of
      lung epithelial cells were found. In the kidney, ethanol did not influence the
      activity of (Na + K)-ATPase or lipid peroxidation, despite the reduction of both
      GSH and the GSH/GSSG ratio. Focally thickened glomerular basement membrane,
      apoptosis of foot processes, and tubulointerstitial fibrosis were found.
      CONCLUSIONS: These data suggest that oxidative stress plays a role in mediating
      the ethanol-induced down-regulation of lung (Na + K)-ATPase. GSH depletion seems
      to be a major determinant of this effect. Independent mechanisms seem to account
      for the morphologic alterations of these organs.

PMID- 11834677
TI  - A systematic review of the effects of bronchodilators on exercise capacity in
      patients with COPD.
AB  - One of the major goals of bronchodilator therapy in patients with COPD is to
      decrease airflow limitation in the airways and, as a consequence, improve dyspnea
      and exercise tolerance. The focus of this systematic review is to assess the
      effects of treatment with beta-agonists, anticholinergics, and theophyllines on
      dyspnea, and steady-state and incremental exercise capacity. Thirty-three, double
      blind, randomized, placebo-controlled studies written in English were selected.
      This review shows that approximately half of the studies showed a significant
      effect of bronchodilator therapy on exercise capacity. Anticholinergic agents
      have significant beneficial effects in the majority of studies, especially when
      measured by steady-state exercise protocols. There is a trend toward a better
      effect of high-dose compared to low-dose anticholinergics. Short-acting beta(2)
      mimetics have favorable effects on exercise capacity in more than two thirds of
      the studies; surprisingly, the situation is less clear for long-acting beta(2)
      agents. The majority of the results of the published reports on theophyllines and
      their effects on exercise are negative. Direct comparisons of different classes
      of bronchodilators have not been made in a sufficient number of studies for a
      rational preference. The addition of a second bronchodilator has no proven
      advantage for improving exercise test results, but this has not been studied
      extensively and not in sufficiently large studies. The majority of studies
      reporting a measure of dyspnea found improvements, even in the absence of
      improvement in exercise capacity.

PMID- 11834678
TI  - COPD and osteoporosis.
AB  - Osteoporosis, with resulting fractures, is a significant problem in patients with
      advanced COPD. The etiology for the bone loss is diverse but includes smoking,
      vitamin D deficiency, low body mass index, hypogonadism, sedentary lifestyle, and
      use of glucocorticoids. Effective strategies to prevent bone loss and/or to treat
      osteoporosis include calcium and vitamin D, hormone replacement when indicated,
      calcitonin, and bisphosphonate administration. However, many patients remain
      undiagnosed until their first fracture because of the lack of recognition of the
      disease. With an increased awareness by pulmonologists and the increased use of
      preventive strategies, the impact of osteoporosis on those patients with COPD
      should decrease.

PMID- 11834679
TI  - Airway hyperresponsiveness and calcium handling by smooth muscle: a "deeper
      look".
AB  - We propose that abnormal calcium handling by the airway smooth muscle may be an
      important determinant of airway hyperresponsiveness. The amplitude, frequency, or
      localization of Ca(2+) oscillations in the smooth muscle may determine the degree
      of airway sensitivity and reactivity, which are characteristic features of
      asthma.

PMID- 11834680
TI  - Oral corticosteroids increase esophageal acid contact times in patients with
      stable asthma.
AB  - STUDY OBJECTIVES: The prevalence of gastroesophageal reflux disease (GERD) is
      higher in people with asthma than in control populations. Predisposing factors
      for GERD development may include asthma medications such as prednisone. The
      objective of this study was to determine whether prednisone alters GERD
      parameters in people with asthma. DESIGN: Prospective, single-blinded, placebo
      controlled, crossover study. SETTING: University medical center clinic.
      PARTICIPANTS: Twenty adults with stable, moderate persistent asthma with minimal
      esophageal reflux symptoms (less than three times a week) who were not receiving
      antireflux therapy. INTERVENTION: Prednisone, 60 mg/d, for 7 days. MEASUREMENTS
      AND RESULTS: Asthma, esophageal reflux symptoms, and spirometry were measured
      during baseline, placebo, and prednisone phases, each 7 days in duration. Dual
      probe esophageal pH monitoring, esophageal and respiratory manometrics (20
      subjects), and basal and stimulated gastric acid secretion (4 subjects) were
      measured after placebo and prednisone phases. There were significant increases in
      esophageal acid contact times at the distal and proximal pH probes during the
      prednisone phase. Total percentage of time that pH was < 4.0 at the distal probe
      was 2.5 +/- 0.4% for placebo compared with 5.9 +/- 0.9% for prednisone (p <
      0.002). Total percentage of time that pH was < 4.0 at the proximal probe was 0.3
      +/- 0.1% for placebo and 0.8 +/- 0.2% for prednisone (p < 0.0007). There were no
      significant changes in subject weight, spirometry, asthma or esophageal reflux
      symptoms, manometrics, or basal or stimulated gastric acid secretion. CONCLUSION:
      Prednisone, 60 mg/d for 7 days, increased esophageal acid contact times in this
      small population of people with stable asthma; however, the mechanism for this
      finding is unclear.

PMID- 11834681
TI  - Video-assisted sleeve lobectomy for mucoepidermoid carcinoma of the left lower
      lobar bronchus: a case report.
AB  - We report what we believe to be the first case of video-assisted sleeve lobectomy
      in an adolescent girl who had experienced recurrent episodes of lobar pneumonia
      and received a diagnosis of low-grade mucoepidermoid carcinoma of the left lower
      lobar bronchus.

PMID- 11834682
TI  - Clinical conference on management dilemmas: bronchiectasis and endobronchial
      polyps.

PMID- 11834683
TI  - Repeated infections in a 68-year-old man.

PMID- 11834684
TI  - Simple construction of a subcutaneous catheter for treatment of severe
      subcutaneous emphysema.
AB  - Subcutaneous emphysema often presents a management dilemma. Rarely, subcutaneous
      emphysema has pathophysiologic consequences. More often, it is extremely
      uncomfortable for the patient, and is often disfiguring and alarming for patients
      and family. When subcutaneous emphysema is severe, physicians may feel compelled
      to treat it, but the currently described techniques are often invasive or
      ineffective. We describe the use of an easily constructed, minimally invasive,
      fenestrated catheter that relieves the symptoms of subcutaneous emphysema.

PMID- 11834685
TI  - Autopsy findings of heart and lungs in a patient with primary pulmonary
      hypertension associated with use of fenfluramine and phentermine.
AB  - A 36-year-old woman (height, 157 cm; weight, 117 kg; body mass index, 47.5)
      received fenfluramine and phentermine (fen-phen) for 7 months, and pulmonary
      hypertension subsequently developed. Her pulmonary arterial pressure was 56 mm
      Hg, and echocardiography showed right ventricular dilatation and hypokinesia.
      Cardiopulmonary arrest developed during right-heart catheterization, and she died
      3 days later. At autopsy, right ventricular dilatation with fibroproliferative
      tricuspid valve was identified. The pulmonary arteries, including the main
      arteries and elastic arteries to the arterioles, revealed fibroproliferative
      plaque; the latter was more severe and more prominent in the upper lobes than in
      the lower lobes. Combined cardiac valvular disease and pulmonary hypertension
      appear to occur frequently in patients receiving fen-phen, and more autopsy cases
      of patients with a history of fen-phen usage are warranted to document the
      frequency of combined cardiac valvular disease and pulmonary hypertension in the
      United States.

PMID- 11834686
TI  - Septic pulmonary embolism associated with periodontal disease: reports of two
      cases and review of the literature.
AB  - We report two cases of septic pulmonary embolism associated with periodontitis.
      Chest CT revealed multiple nodular shadows with features characteristic of septic
      pulmonary embolism in both patients. Both patients had toothache, fever, and
      chest pain, and showed findings of periodontitis at initial presentation.
      Antimicrobial agents combined with dental surgery were successful in treatment.
      While septic pulmonary embolism from the lesions of periodontitis appears to be
      rare, periodontitis remains important in the differential diagnosis of septic
      pulmonary embolism.

PMID- 11834687
TI  - Choriocarcinoma in the pulmonary artery treated with emergency pulmonary
      embolectomy.
AB  - A 42-year-old woman with choriocarcinoma required emergency pulmonary embolectomy
      under cardiopulmonary bypass. After diagnosis of choriocarcinoma was confirmed by
      examination of tumor emboli specimens, the patient was treated and had complete
      remission by chemotherapy over a 6-month period. Although rare, choriocarcinoma
      should be considered in the differential diagnosis of fertile women presenting
      with pulmonary embolism.

PMID- 11834688
TI  - Pulmonary edema caused by inhaled nitric oxide therapy in two patients with
      pulmonary hypertension associated with the CREST syndrome.
AB  - Pulmonary arterial hypertension (PAH) is commonly associated with the CREST
      (calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly,
      telangiectasia) syndrome. Inhaled nitric oxide (iNO) is often used to assess
      acute vasoresponsiveness in patients with PAH, and reports of adverse reactions
      have been infrequent. We describe two of nine patients with PAH and CREST
      syndrome who had pulmonary edema develop during acute iNO testing. This
      complication was not encountered in the 46 patients with other forms of PAH
      tested with iNO. We suggest that iNO should be used with caution, if at all, to
      test acute vasoreactivity in patients with CREST syndrome.

PMID- 11834689
TI  - Diffuse panbronchiolitis: a treatable sinobronchial disease in need of
      recognition in the United States.
AB  - Diffuse panbronchiolitis (DPB) is a progressive inflammatory disease, well
      recognized in Japan, characterized by sinusitis and obstructive small airway
      disease; if left untreated, it progresses to bronchiectasis, respiratory failure,
      and death. Treatment using low-dose erythromycin has proven to be highly
      efficacious. Lack of familiarity with DPB in the United States may result in the
      failure to correctly diagnose and treat this disorder. We describe a Cambodian
      man in whom the characteristic imaging and histologic features of DPB were
      elicited but not recognized in spite of evaluation at a referral center. When DPB
      was diagnosed 6 years later, he was in respiratory failure, but made an excellent
      recovery once erythromycin therapy was instituted. We report this case to
      increase physician awareness of DPB as a cause of sinobronchial disease and
      discuss its diagnostic features so that the disease is recognized and treated
      without delay.

PMID- 11834690
TI  - Defining dyspnea.

PMID- 11834691
TI  - Supplemental oxygen during flexible bronchoscopy.

PMID- 11834692
TI  - Endobronchial spread of parenchymal metastases.

PMID- 11834693
TI  - Pectus and hypoventilation.

PMID- 11834694
TI  - Enoxaparin treatment in unstable coronary artery disease: international cost
      savings.

PMID- 11834695
TI  - Status asthmaticus in children: evidence-based recommendations.

PMID- 11834696
TI  - Pneumothorax--guidelines of action.

PMID- 11834700
TI  - Na(+)-Ca(2+) exchange: three new tools.

PMID- 11834701
TI  - Can tissue engineering mend broken hearts?

PMID- 11834702
TI  - Out phoxing the endothelium: what's left without p47?

PMID- 11834703
TI  - C/EBP-beta mediates iNOS induction by hypoxia in rat pulmonary microvascular
      smooth muscle cells.
AB  - Exposure of rats to 10% O(2) for 4 days caused pulmonary hypertension and induced
      expression of both inducible nitric oxide synthase (iNOS) and CCAAT box enhancer
      binding protein-beta (C/EBP-beta) in rat lung. Electrophoretic mobility shift
      assays (EMSAs) showed that exposure to 1% O(2) increased the C/EBP-beta binding
      in rat pulmonary microvascular smooth muscle cells (rPSMs). To test the
      hypothesis that C/EBP-beta participates in hypoxia-induced iNOS expression in
      rPSMs, a C/EBP motif at -910 bp of rat iNOS promoter was mutated. rPSMs
      transfected with the rat iNOS promoter and exposed to 1% O(2) for 24 hours had
      significantly increased wild-type iNOS promoter activity. The hypoxia-induced
      promoter activity was abolished by the C/EBP motif mutation. Thus, C/EBP-beta
      mediates, at least in part, hypoxia-induced iNOS expression in rPSMs.

PMID- 11834704
TI  - Cardiotrophin-1 stimulation of cardiac fibroblast growth: roles for glycoprotein
      130/leukemia inhibitory factor receptor and the endothelin type A receptor.
AB  - Cardiotrophin-1 (CT-1), a member of the interleukin-6 superfamily, and endothelin
      1 (ET-1) are potent hypertrophic factors in cardiomyocytes. Although CT-1 and ET
      1 gene expression in the heart is upregulated in experimental heart failure,
      their role in the activation of the cardiac fibroblast is unknown. This study was
      designed to identify the presence and action of CT-1 and its receptor complex,
      glycoprotein130 (gp130) and leukemia inhibitory factor (LIF) receptor, on cardiac
      fibroblast growth in cultured adult canine cardiac fibroblasts. In addition, we
      investigated the interaction between CT-1/gp130/LIF receptor and ET-1/endothelin
      type A (ET(A)) receptor axis. Immunohistochemistry was performed using the
      indirect immunoperoxidase method, while we assessed the cell cycle of cardiac
      fibroblasts by flow cytometry, DNA synthesis by [(3)H]thymidine incorporation,
      and collagen synthesis by [(3)H]proline incorporation, respectively. CT-1 and
      gp130/LIF receptor were widely present in the cytoplasm of the cardiac
      fibroblasts. Exogenous CT-1 markedly stimulated [(3)H]thymidine and [(3)H]proline
      incorporations (P<0.01), with accumulation of cells in the S phase. Blockade of
      gp130 or LIF receptor inhibited basal growth as well as CT-1- or ET-1-stimulated
      cardiac fibroblast growth. The specific ET(A) receptor antagonist, BQ123,
      significantly inhibited CT-1-stimulated DNA synthesis. This study demonstrates
      that CT-1 and its receptors are present in cardiac fibroblasts. In addition,
      growth of these cells stimulated by endogenous and exogenous CT-1 requires
      gp130/LIF receptor as well as ET(A) receptor activation. We conclude that
      gp130/LIF receptor and ET(A) receptor activation are essential for cardiac
      fibroblast growth by CT-1 and that there is synergism with ET-1/ET(A) receptor
      axis.

PMID- 11834705
TI  - Adenoviral-directed expression of the type 1A angiotensin receptor promotes
      cardiomyocyte hypertrophy via transactivation of the epidermal growth factor
      receptor.
AB  - Angiotensin II (Ang II) may cause cardiac hypertrophy via type 1 Ang II receptors
      (AT(1)) on cardiomyocytes and through growth factors released from cardiac
      fibroblasts. Whereas cardiomyocyte-specific AT(1) receptor expression produces
      cardiac hypertrophy and remodeling in vivo, delineation of the signals that
      mediate growth to Ang II is challenging because the prevailing in vitro model
      (cultured neonatal cardiomyocytes) expresses low levels of AT(1) receptor and
      responds inconsistently to Ang II. In this study, when AT(1A) receptors were
      expressed using adenovirus in cultured neonatal cardiomyocytes, Ang II stimulated
      a robust hypertrophy that was not secondary to the release of cardiac fibroblast
      derived factors, specifically endothelin-1. Hypertrophy was accompanied by the
      induction of the immediate-early response genes, c-fos and c-jun, and
      reexpression of atrial natriuretic peptide (ANP). Ang II-induced activation of an
      ANP promoter-reporter was inhibited by the dominant/negative mutants, GalphaqI
      and N17Ras, indicating that hypertrophic signaling by the AT(1A) receptor is via
      heterotrimeric G protein coupling and downstream Ras pathways. AT(1A)-mediated
      cardiomyocyte hypertrophy and mitogen-activated protein kinase (MAPK) activation
      were inhibited by the MAPK kinase inhibitor, PD98059, and the epidermal growth
      factor (EGF) receptor kinase antagonist, AG1478, but not by PKC inhibitor,
      bisindolylmaleimide-1. Moreover, Ang II-induced MAPK activation was prevented by
      treatment with a matrix metalloproteinase inhibitor, consistent with the tyrosine
      phosphorylation of the EGF receptor in response to AT(1A) receptor activation.
      These data unequivocally demonstrate that Ang II can directly promote cardiac
      myocyte growth via AT(1A) receptors expressed on these cells and reveal for the
      first time the important contribution of EGF receptor-transactivated MAPK
      signaling to this process.

PMID- 11834706
TI  - Essential role of the NADPH oxidase subunit p47(phox) in endothelial cell
      superoxide production in response to phorbol ester and tumor necrosis factor
      alpha.
AB  - A phagocyte-type NADPH oxidase complex is a major source of endothelial reactive
      oxygen species (ROS) production, but its biochemical function and regulation
      remain unclear. In neutrophils, the p47(phox) subunit is centrally involved in
      oxidase activation in response to agonists such as phorbol-12-myristate-13
      acetate (PMA). We investigated the role of p47(phox) in endothelial cell ROS
      production in response to PMA or tumor necrosis factor-alpha (TNFalpha)
      stimulation. To specifically address the role of p47(phox), we studied coronary
      microvascular endothelial cells (CMECs) isolated from p47(phox-/-) mice and wild
      type controls. p47(phox) was absent in hearts of knockout mice whereas the
      essential oxidase subunit, p22(phox), was expressed in both groups. In the
      absence of agonist stimulation, the lack of p47(phox) did not result in a
      reduction in NADPH-dependent ROS production in p47(phox-/-) CMECs compared with
      wild-type CMECs. Prestimulation with PMA (100 ng/mL) or TNFalpha (100 U/mL) for
      10 minutes significantly increased NADPH-dependent O(2)(-) production in wild
      type CMECs, assessed either by lucigenin (5 micromol/L) chemiluminescence or
      dichlorohydrofluorescein (DCF) fluorescence. This response was completely lost in
      p47(phox-/-) cells. Transfection of the full-length p47(phox) cDNA into p47(phox
      /-) CMECs caused expression of p47(phox) protein and restoration of the O(2)(-)
      response to PMA and TNFalpha. In wild-type CMECs, transfection of antisense
      p47(phox) cDNA substantially reduced p47(phox) expression and caused loss of the
      O(2)(-) response to PMA and TNFalpha. These data show that endothelial cell
      p47(phox) is critical in the upregulation of NADPH oxidase activity by PMA and
      TNFalpha.

PMID- 11834707
TI  - Cyclic nucleotide phosphodiesterase 1C promotes human arterial smooth muscle cell
      proliferation.
AB  - Proliferation of arterial smooth muscle cells (SMCs) is a key event in the
      formation of advanced atherosclerotic lesions and restenosis after angioplasty.
      Cyclic nucleotides (cAMP and cGMP) inhibit arterial SMC proliferation, and
      elevation of cyclic nucleotides reduces neointimal formation after angioplasty in
      animal models. Degradation of cAMP and cGMP is catalyzed by cyclic nucleotide
      phosphodiesterases (PDEs). One of these, PDE1C, hydrolyzes cAMP and cGMP and is
      expressed in proliferating human SMCs but is absent in quiescent human aorta.
      Thus, PDE1C expression is low in cultured human SMCs made quiescent by attaching
      to fibrillar collagen type I. After release from the fibrillar collagen, PDE1C
      expression is induced and associated with traverse through S-phase of the cell
      cycle. Further, PDE1C is expressed in vivo in human fetal aorta containing
      proliferating SMCs, but not in newborn aorta in which SMC proliferation has
      ceased. Inhibition of PDE1C in SMCs isolated from normal aorta or from lesions of
      atherosclerosis using antisense oligonucleotides or a PDE1 inhibitor results in
      suppression of SMC proliferation. In conclusion, PDE1C expression is a marker of
      human SMC proliferation ex vivo and in vivo. Inhibition of PDE1C leads to
      inhibition of human SMC proliferation. Because PDE1C is absent in quiescent SMCs,
      PDE1C inhibitors may target proliferating SMCs in lesions of atherosclerosis or
      restenosis.

PMID- 11834708
TI  - Cardiac-specific expression and hypertrophic upregulation of the feline Na(+)
      Ca(2+) exchanger gene H1-promoter in a transgenic mouse model.
AB  - The NCX1 gene contains three promoters (H1, K1, and Br1), and as a result of
      alternative promoter usage and alternative splicing, there are multiple tissue
      specific variants of the Na(+)-Ca(2+) exchanger. We have proposed that for NCX1,
      the H1 promoter regulates expression in the heart, the K1 promoter regulates
      expression in the kidney, and the Br1 promoter regulates expression in the brain
      as well as low-level ubiquitous expression. Here, using a transgenic mouse model,
      we test the role of the DNA region including -1831 to 67 bp of intron 1,
      encompassing exon H1 of the feline NCX1 gene (NCX1H1). The NCX1H1 promoter was
      sufficient for driving the normal spatiotemporal pattern of NCX1 expression in
      cardiac development. The luciferase reporter gene was expressed in a heart
      restricted pattern both in early embryos (embryonic days 8 to 14) and in later
      embryos (after embryonic day 14), when NCX1 is also expressed in other tissues.
      In the adult, no luciferase activity was detected in the kidney, liver, spleen,
      uterus, or skeletal muscle; minimal activity was detected in the brain; and very
      high levels of luciferase expression were detected in the heart. Transverse
      aortic constriction-operated mice showed significantly increased left ventricular
      mass after 7 days. In addition, there was a 2-fold upregulation of NCX1H1
      promoter activity in the left ventricle in animals after 7 days of pressure
      overload compared with both control and sham-operated animals. This work
      demonstrates that the NCX1H1 promoter directs cardiac-specific expression of the
      exchanger in both the embryo and adult and is also sufficient for the
      upregulation of NCX1 in response to pressure overload.

PMID- 11834709
TI  - Modulation of Ca(2+) release in cardiac myocytes by changes in repolarization
      rate: role of phase-1 action potential repolarization in excitation-contraction
      coupling.
AB  - The early rate of action potential (AP) repolarization varies in the mammalian
      heart regionally, during development, and in disease. We used confocal microscopy
      to assess the effects of changes in repolarization rate on spatially resolved
      sarcoplasmic reticulum (SR) Ca(2+) release. The kinetics and peak amplitude of
      Ca(2+) transients were reduced, and the amplitude, frequency, and temporal
      synchronization of Ca(2+) spikes decreased as the rate of repolarization was
      slowed. The first latencies and temporal dispersion of Ca(2+) spikes tracked
      closely with the time to peak and the width of the L-type Ca(2+) current
      (I(Ca,L)), suggesting that the effects of repolarization on excitation
      contraction coupling occur primarily via changes in I(Ca,L). Next, we examined
      the effect of changes in the rapid early repolarization rate (phase 1) of a model
      human AP on SR Ca(2+) release by varying the amount of transient outward K(+)
      current. Slowing of phase-1 repolarization also caused a loss of temporal
      synchrony and recruitment of Ca(2+)-release events, associated with a reduced
      amplitude and lengthened time to peak of I(Ca,L). Isoproterenol application
      enhanced and largely resynchronized SR Ca(2+) release, while it increased the
      magnitude and shortened the time to peak of I(Ca,L). Our data demonstrate that
      membrane repolarization modulates the recruitment and synchronization of SR
      Ca(2+) release via I(Ca,L) and illustrate a physiological role for the phase-1
      notch of the AP in optimizing temporal summation and recruitment of Ca(2+)
      release events. The effects of slowing phase-1 repolarization can be overcome by
      beta-adrenergic stimulation.

PMID- 11834710
TI  - Ca(2+) signaling in cardiac myocytes overexpressing the alpha(1) subunit of L
      type Ca(2+) channel.
AB  - Voltage-gated L-type Ca(2+) channels (LCCs) provide Ca(2+) ingress into cardiac
      myocytes and play a key role in intracellular Ca(2+) homeostasis and excitation
      contraction coupling. We investigated the effects of a constitutive increase of
      LCC density on Ca(2+) signaling in ventricular myocytes from 4-month-old
      transgenic (Tg) mice overexpressing the alpha(1) subunit of LCC in the heart. At
      this age, cells were somewhat hypertrophic as reflected by a 20% increase in cell
      capacitance relative to those from nontransgenic (Ntg) littermates. Whole cell
      I(Ca) density in Tg myocytes was elevated by 48% at 0 mV compared with the Ntg
      group. Single-channel analysis detected an increase in LCC density with similar
      conductance and gating properties. Although the overexpressed LCCs triggered an
      augmented SR Ca(2+) release, the "gain" function of EC coupling was
      uncompromised, and SR Ca(2+) content, diastolic cytosolic Ca(2+), and unitary
      properties of Ca(2+) sparks were unchanged. Importantly, the enhanced I(Ca) entry
      and SR Ca(2+) release were associated with an upregulation of the Na(+)-Ca(2+)
      exchange activity (indexed by the half decay time of caffeine-elicited Ca(2+)
      transient) by 27% and SR Ca(2+) recycling by approximately 35%. Western analysis
      detected a 53% increase in the Na(+)-Ca(2+) exchanger expression but no change in
      the abundance of ryanodine receptor (RyR), SERCA2, and phospholamban. Analysis of
      I(Ca) kinetics suggested that SR Ca(2+) release-dependent inactivation of LCCs
      remains intact in Tg cells. Thus, in spite of the modest cardiac hypertrophy, the
      overexpressed LCCs form functional coupling with RyRs, preserving both orthograde
      and retrograde Ca(2+) signaling between LCCs and RyRs. These results also suggest
      that a modest but sustained increase in Ca(2+) influx triggers a coordinated
      remodeling of Ca(2+) handling to maintain Ca(2+) homeostasis.

PMID- 11834711
TI  - Na(+)-Ca(2+) exchange current and submembrane [Ca(2+)] during the cardiac action
      potential.
AB  - Na(+)-Ca(2+) exchange (NCX) is crucial in the regulation of [Ca(2+)](i) and
      cardiac contractility, but key details of its dynamic function during the
      heartbeat are not known. In the present study, we assess how NCX current (I(NCX))
      varies during a rabbit ventricular action potential (AP). First, we measured the
      steady-state voltage and [Ca(2+)](i) dependence of I(NCX) under conditions when
      [Ca(2+)](i) was heavily buffered. We then used this relationship to infer the
      submembrane [Ca(2+)](i) ([Ca(2+)](sm)) sensed by NCX during a normal AP and
      [Ca(2+)](i) transient (when the AP was interrupted to produce an I(NCX) tail
      current). The [Ca(2+)](i) dependence of I(NCX) at -90 mV allowed us to convert
      the peak inward I(NCX) tail currents to [Ca(2+)](sm). Peak [Ca(2+)](sm) measured
      via this technique was >3.2 micromol/L within < 32 ms of the AP upstroke (versus
      peak [Ca(2+)](i) of 1.1 micromol/L at 81 ms measured with the global Ca(2+)
      indicator indo-1). The voltage and [Ca(2+)](sm) dependence of I(NCX) allowed us
      to infer I(NCX) during the normal AP and Ca(2+) transient. The early rise in
      [Ca(2+)](sm) causes I(NCX) to be inward for the majority of the AP. Thus, little
      Ca(2+) influx via NCX is expected under physiological conditions, but this can
      differ among species and in pathophysiological conditions.

PMID- 11834713
TI  - Loss of p53 accelerates neointimal lesions of vein bypass grafts in mice.
AB  - The transcription factor p53 is essentially involved in regulation of cell death
      and proliferation. Recently, we have established a mouse model for vein graft
      arteriosclerosis by grafting autologous jugular veins or vena cava to carotid
      arteries. Using this model, we studied the role of p53 in the development of vein
      graft arteriosclerosis in p53(-/-) mice. Four weeks after grafting, neointimal
      hyperplasia of vein grafts in p53(-/-) mice was increased 2-fold compared with
      that of wild-type controls. Cell component analysis revealed that neointimal
      lesions in p53(-/-) mice consisted mainly of alpha-actin positive smooth muscle
      cells (SMCs), whereas the majority of cells in wild-type mice were MAC-1
      (CD11b/18)-positive at 4 weeks. Importantly, SMC apoptosis as determined by TUNEL
      assay was significantly reduced in p53(-/-) vein grafts. TUNEL positive cells in
      wild-type vein grafts markedly increased from 0.5% to 6.4% of total cells 4 weeks
      postoperatively, but remained virtually unchanged in p53(-/-) grafts (0.8%).
      Immunofluorescence analysis revealed that increased p53 expression in neointimal
      SMCs of wild-type, but not p53(-/-), mice coincided with oxidative DNA damage in
      vein grafts. Interestingly, SMCs of p53(-/-) mice showed increased apoptosis in
      response to TNFalpha and decreased apoptosis in response to sodium nitroprusside.
      Additionally, p53-deficient SMCs showed a higher rate of proliferation and
      migration and expressed higher levels of matrix metalloproteinases. Thus, p53
      deficiency accelerates neointima formation by facilitating SMC proliferation as
      well as abrogating cell apoptosis.

PMID- 11834712
TI  - p38 Mitogen-activated protein kinase mediates a negative inotropic effect in
      cardiac myocytes.
AB  - p38 Mitogen-activated protein kinase (MAPK) is one of the most ancient signaling
      molecules and is involved in multiple cellular processes, including cell
      proliferation, cell growth, and cell death. In the heart, enhanced activation of
      p38 MAPK is associated with ischemia/reperfusion injury and the onset of heart
      failure. In the present study, we investigated the function of p38 MAPK in
      regulating cardiac contractility and its underlying mechanisms. In cultured adult
      rat cardiomyocytes, activation of p38 MAPK by adenoviral gene transfer of an
      activated mutant of its upstream kinase, MKK3bE, led to a significant reduction
      in baseline contractility, compared with uninfected cells or those infected with
      a control adenoviral vector (Adv-beta-galactosidase). The inhibitory effect of
      MKK3bE on contractility was largely prevented by coexpressing a dominant-negative
      mutant of p38 MAPK or treating cells with a p38 MAPK inhibitor, SB203580.
      Conversely, inhibition of endogenous p38 MAPK activity by SB203580 rapidly and
      reversibly enhanced cell contractility in a dose-dependent manner, without
      altering L-type Ca(2+) currents or Ca(2+)(i) transients. MKK3bE-induced p38
      activation had no significant effect on pH(i), whereas SB203580 had a minor
      effect to elevate pH(i). Furthermore, activation of p38 MAPK was unable to
      increase troponin I phosphorylation. Thus, we conclude that the negative
      inotropic effect of p38 MAPK is mediated by decreasing myofilament response to
      Ca(2+), rather than by altering Ca(2+)(i) homeostasis and that the reduced
      myofilament Ca(2+) sensitivity is unlikely attributable to troponin I
      phosphorylation or alterations in pH(i). These findings reveal a novel function
      of p38 MAPK and shed a new light on our understanding of the coincidence of p38
      MAPK activation and the onset of heart failure.

PMID- 11834714
TI  - Early loss of thrombomodulin expression impairs vein graft thromboresistance:
      implications for vein graft failure.
AB  - Thrombosis is the major cause of early vein graft failure. Our aim was to
      determine whether alterations in the expression of the anticoagulant proteins,
      thrombomodulin (TM) and the endothelial cell protein C receptor (EPCR), impair
      endothelial thromboresistance that may contribute to vein graft failure.
      Immunohistochemical staining of autologous rabbit vein graft sections revealed
      that the expression of TM, but not EPCR, was reduced significantly early after
      graft implantation. Western blot analysis revealed that TM expression was reduced
      by >95% during the first 2 weeks after implantation, with gradual but incomplete
      recovery by 42 days. This resulted in up to a 95% reduction in the capacity of
      the grafts to activate protein C and was associated with an increase in bound
      thrombin activity, which peaked on day 7 at 28.7 +/- 3.8 mU/cm(2) and remained
      elevated for more than 14 days. Restoration of TM expression using adenovirus
      vector-mediated gene transfer significantly enhanced the capacity of grafts to
      activate protein C and reduced bound thrombin activity on day 7 to levels
      comparable to that of normal veins (5.7 +/- 0.4 versus 5.2 +/- 1.1 mU/cm(2),
      respectively, P=0.74). Surprisingly, neointima formation was not affected by this
      inhibition of local thrombin activity. These data suggest that the early loss of
      TM expression significantly impairs vein graft thromboresistance and results in
      enhanced local thrombin generation. Although enhanced local thrombin generation
      may predispose to early vein graft failure due to thrombosis, it does not seem to
      contribute significantly to late vein graft failure due to neointimal
      hyperplasia.

PMID- 11834715
TI  - Frequency analysis of ventricular fibrillation in Swine ventricles.
AB  - It has been suggested from frequency analysis that cardiac fibrillation is driven
      by stable intramural reentry, with wavebreak occurring due to failure of 1:1
      propagation. We tested this hypothesis with a combined experimental and
      theoretical approach. Optical mapping was performed on epicardial, endocardial,
      and transmural cut surfaces of fibrillating swine ventricles. Wavelets were
      characterized, the frequency content of optical signals analyzed, and space-time
      plots (STPs) constructed to detect Wenckebach-like conduction. The findings were
      compared with simulations in 2D and 3D cardiac tissue using the Luo-Rudy action
      potential model. The incidence of reentry in the cut transmural surface (11.8% in
      right ventricle, 14.3% in left ventricle) was similar to that on the endocardial
      surface (13.1%, P=NS) but greater than on the epicardial surface (7.7%, P<0.01).
      Frequency spectra of optically recorded membrane voltage were organized into
      spatial domains with the same dominant frequency, but these domains were
      nonstationary. In STPs, pseudo-2:1 conduction block was caused by double
      potentials arising when reentry occurred on the recording site rather than true
      Wenckebach conduction. The latter was observed in 11 of 166 STPs but did not
      occur at borders of high-to-low frequency domains. In simulations, similar
      findings were obtained when action potential duration (APD) restitution slope was
      steep. Stationary dominant frequency domains with Wenckebach conduction patterns
      were observed only in the presence of shallow APD restitution slope and marked
      nonuniform tissue heterogeneity. In conclusion, stable intramural reentry as the
      engine of fibrillation was not observed. Our findings support the idea that
      dynamic wavebreak plays a fundamental role in the generation and maintenance of
      ventricular fibrillation.

PMID- 11834716
TI  - Tissue engineering of a differentiated cardiac muscle construct.
AB  - Cardiac tissue engineering is an emerging field. The suitability of engineered
      heart tissue (EHT) for both in vitro and in vivo applications will depend on the
      degree of syncytoid tissue formation and cardiac myocyte differentiation in
      vitro, contractile function, and electrophysiological properties. Here, we
      demonstrate that cardiac myocytes from neonatal rats, when mixed with collagen I
      and matrix factors, cast in circular molds, and subjected to phasic mechanical
      stretch, reconstitute ring-shaped EHTs that display important hallmarks of
      differentiated myocardium. Comparative histological analysis of EHTs with native
      heart tissue from newborn, 6-day-old, and adult rats revealed that cardiac cells
      in EHTs reconstitute intensively interconnected, longitudinally oriented, cardiac
      muscle bundles with morphological features resembling adult rather than immature
      native tissue. Confocal and electron microscopy demonstrated characteristic
      features of native differentiated myocardium; some of these features are absent
      in myocytes from newborn rats: (1) highly organized sarcomeres in registry; (2)
      adherens junctions, gap junctions, and desmosomes; (3) a well-developed T-tubular
      system and dyad formation with the sarcoplasmic reticulum; and (4) a basement
      membrane surrounding cardiac myocytes. Accordingly, EHTs displayed contractile
      characteristics of native myocardium with a high ratio of twitch (0.4 to 0.8 mN)
      to resting tension (0.1 to 0.3 mN) and a strong beta-adrenergic inotropic
      response. Action potential recordings demonstrated stable resting membrane
      potentials of -66 to -78 mV, fast upstroke kinetics, and a prominent plateau
      phase. The data indicate that EHTs represent highly differentiated cardiac tissue
      constructs, making EHTs a promising material for in vitro studies of cardiac
      function and tissue replacement therapy.

PMID- 11834717
TI  - Effect of ATP-sensitive potassium channel inhibition on resting coronary vascular
      responses in humans.
AB  - Experimental data suggest that vascular ATP-sensitive potassium (K(ATP)) channels
      regulate coronary blood flow (CBF), but their role in regulating human CBF is
      unclear. We sought to determine the contribution of K(ATP) channels to resting
      conduit vessel and microvascular function in the human coronary circulation.
      Twenty-five patients (19 male/6 female, aged 56 +/- 12 years) were recruited.
      Systemic and coronary hemodynamics were assessed in 20 patients before and after
      K(ATP) channel inhibition with graded intracoronary glibenclamide infusions (4,
      16, and 40 microg/min), in an angiographically smooth or mildly stenosed coronary
      artery following successful elective percutaneous coronary intervention to
      another vessel. Coronary blood velocity was measured with a Doppler guidewire and
      CBF calculated. Adenosine-induced hyperemia was determined following bolus
      intracoronary adenosine injection (24 microg). Time control studies were
      undertaken in 5 patients. Compared with vehicle infusion (0.9% saline),
      glibenclamide reduced resting conduit vessel diameter from 2.5 +/- 0.1 to 2.3 +/-
      0.1 mm (P<0.01), resting CBF by 17% (P=0.05), and resting CBF corrected for rate
      pressure-product by 18% (P=0.01) in a dose-dependent manner. A corresponding 24%
      increase in coronary vascular resistance was noted at the highest dose (P<0.01).
      No alteration to resting CBF was noted in the time control studies. Glibenclamide
      reduced peak adenosine-induced hyperemia (P=0.01) but did not alter coronary flow
      reserve. Plasma insulin increased from 5.6 +/- 1.2 to 7.6 +/- 1.3 mU/L (P=0.02);
      however, plasma glucose was unchanged. Vascular K(ATP) channels are involved in
      the maintenance of basal coronary tone but may not be essential to adenosine
      induced coronary hyperemia in humans.

PMID- 11834719
TI  - Carbon monoxide-releasing molecules: characterization of biochemical and vascular
      activities.
AB  - Carbon monoxide (CO) is generated in living organisms during the degradation of
      heme by the enzyme heme oxygenase, which exists in constitutive (HO-2 and HO-3)
      and inducible (HO-1) isoforms. Carbon monoxide gas is known to dilate blood
      vessels in a manner similar to nitric oxide and has been recently shown to
      possess antiinflammatory and antiapoptotic properties. We report that a series of
      transition metal carbonyls, termed here carbon monoxide-releasing molecules (CO
      RMs), liberate CO to elicit direct biological activities. Specifically,
      spectrophotometric and NMR analysis revealed that dimanganese decacarbonyl and
      tricarbonyldichlororuthenium (II) dimer release CO in a concentration-dependent
      manner. Moreover, CO-RMs caused sustained vasodilation in precontracted rat
      aortic rings, attenuated coronary vasoconstriction in hearts ex vivo, and
      significantly reduced acute hypertension in vivo. These vascular effects were
      mimicked by induction of HO-1 after treatment of animals with hemin, which
      increases endogenously generated CO. Thus, we have identified a novel class of
      compounds that are useful as prototypes for studying the bioactivity of CO. In
      the long term, transition metal carbonyls could be utilized for the therapeutic
      delivery of CO to alleviate vascular- and immuno-related dysfunctions. The full
      text of this article is available at http://www.circresaha.org.

PMID- 11834720
TI  - Early expression of myocardial HIF-1alpha in response to mechanical stresses:
      regulation by stretch-activated channels and the phosphatidylinositol 3-kinase
      signaling pathway.
AB  - Vascular endothelial growth factor (VEGF) expression is upregulated by hypoxia
      inducible factor-1 (HIF-1) in ischemic tissues and growing tumors. Normally, HIF
      1 activity depends on the amount of HIF-1alpha subunit, which is tightly
      regulated by the oxygen tension. In the myocardium, VEGF expression has been
      shown to be induced under nonhypoxic conditions by mechanical stresses. However,
      the cellular mechanism of stress-mediated VEGF induction remains unclear.
      Therefore, we examined the possible involvement of HIF-1 in stress-mediated VEGF
      induction in rat hearts. In this study, we increased the left ventricular wall
      tension using 3 different methods, namely by inducing regional ischemia, by
      expanding an intraventricular balloon, and by producing hemodynamic overload
      using an aortocaval shunt. In all cases, HIF-1alpha accumulated in the nuclei of
      cardiac myocytes in the early phase, and this was followed by VEGF induction.
      Phosphatidylinositol 3-kinase (PI3K)-dependent Akt phosphorylation was found to
      be activated by mechanical stress and completely blocked by wortmannin (a PI3K
      inhibitor). Moreover, the stress-mediated induction of HIF-1alpha and VEGF was
      suppressed by gadolinium (a stretch-activated channel inhibitor), wortmannin, and
      rapamycin (a FRAP inhibitor). Our results suggest that HIF-1alpha plays an
      important role in the induction of VEGF in nonischemic and mechanically stressed
      myocardium, and that this is regulated by stretch-activated channels and the
      PI3K/Akt/FRAP pathway. Moreover, this signaling pathway, which induces HIF
      1alpha, seems to play an important role in the adaptation of the myocardium to
      stresses. The full text of this article is available at
      http://www.circresaha.org.

PMID- 11834721
TI  - Interleukin-18 enhances atherosclerosis in apolipoprotein E(-/-) mice through
      release of interferon-gamma.
AB  - We have previously shown that interferon-gamma (IFN-gamma) is a potent enhancer
      of atherogenesis. Interleukin-18 (IL-18) promotes inflammatory responses through
      release of IFN-gamma, although it can also exert direct actions on other
      inflammatory mediators. In this present study, we determined the effects of IL-18
      on atherogenesis and the role of IFN-gamma in this response. Male apolipoprotein
      E(-/-) mice (apoE(-/-); aged 16 weeks, n=10/group) were fed a normal diet and
      injected intraperitoneally for 30 days with either recombinant IL-18 (30
      ng/g/day) or saline. Atherosclerotic lesion size was quantified in 2 vascular
      beds: the ascending aorta and the aortic arch. IL-18 administration did not
      affect serum cholesterol concentrations or lipoprotein-cholesterol distribution;
      however, exogenous IL-18 administration increased lesion size 2-fold in both the
      ascending aorta (50 642 +/- 12 515 versus 112 399 +/- 13 227 microm(2) P=0.004;
      saline versus IL-18 groups, respectively) and the aortic arch (3.1 +/- 0.3%
      versus 6.2 +/- 0.9% area, P=0.006). Exogenous IL-18 promoted a 4-fold increase in
      the number of lesion-associated T lymphocytes (11 +/- 3 versus 50 +/- 5 cells;
      P<0.0001) and cells expressing major histocompatability complex class II (9 +/- 3
      versus 40 +/- 6 cells; P=0.0002). To determine the role of IFN-gamma production
      in this response, exogenous IL-18 was administered to apoE(-/-) mice that were
      IFN-gamma deficient. These studies demonstrated that lack of endogenous IFN-gamma
      ablated the effects of IL-18 on atherosclerosis. Therefore, these data strongly
      implicates IL-18 in the atherogenic process and suggests that IL-18 increases
      lesion development through enhancement of an inflammatory response involving an
      IFN-gamma-dependent mechanism. The full text of this article is available at
      http://www.circresaha.org.

PMID- 11834722
TI  - Unusual alternative splicing within the human kallikrein genes KLK2 and KLK3
      gives rise to novel prostate-specific proteins.
AB  - Prostate-specific antigen (PSA) and human kallikrein 2 are closely related
      products of the human kallikrein genes KLK3 and KLK2, respectively. Both PSA and
      human kallikrein 2 are produced and secreted in the prostate and have important
      applications in the diagnosis of prostate cancer. We report here the
      identification of unusual mRNA splice variants of the KLK2 and KLK3 genes that
      result from inclusion of intronic sequences adjacent to the first exon. The novel
      proteins encoded by these transcripts, named PSA-linked molecule (PSA-LM) and hK2
      linked molecule (K-LM), share only the signal peptide with the original protein
      product of the respective gene. The mature proteins are entirely different and
      bear no similarity to the kallikrein family or to other proteins in the
      databases. As is the case with PSA, PSA-LM is expressed in the secretory
      epithelial cells of the prostate and is up-regulated in response to androgenic
      stimulation. A similar pattern of expression is suggested for K-LM.

PMID- 11834723
TI  - Analysis of gene expression profile induced by hepatocyte nuclear factor 4alpha
      in hepatoma cells using an oligonucleotide microarray.
AB  - Hepatocyte nuclear factor 4alpha (HNF-4alpha), a liver-specific transcription
      factor, plays a significant role in many liver-specific functions, including
      lipid, glucose, drug, and ammonia metabolism, and also in embryonal liver
      development. However, its functions and regulation are not yet clearly
      understood. In this study, we constructed an adenovirus vector carrying rat HNF
      4alpha cDNA and transfected the adenovirus to human hepatoma cells, HuH-7, to
      enforce expression of the exogenous HNF-4alpha gene. We analyzed HNF-4alpha
      induced genes using cDNA microarray technology, which included over 9000 genes.
      As a result, 62 genes showed a greater than 2.0-fold change in expression level
      after the viral transfection. Fifty-six genes were consistently induced by HNF
      4alpha overexpression, and six genes were repressed. To assess HNF-4alpha
      function, we attempted to classify the genes, which had been classified by their
      encoding protein functions in a previous report. We could classify 45 genes. The
      rest of the HNF-4alpha-sensitive genes were unclassified (4 genes) or not
      identified (13 genes). Among the classified genes, almost half of the induced
      genes (26 of 40) were related to metabolism genes and particularly to lipid
      metabolism-related genes. This cDNA microarray analysis showed that HNF-4alpha is
      one of the central liver metabolism regulators.

PMID- 11834724
TI  - Homologous pairing and ring and filament structure formation activities of the
      human Xrcc2*Rad51D complex.
AB  - The Xrcc2 and Rad51D/Rad51L3 proteins, which belong to the Rad51 paralogs, are
      required for homologous recombinational repair (HRR) in vertebrates. The Xrcc2
      and Rad51D/Rad51L3 genes, whose products interact with each other, have essential
      roles in ensuring normal embryonic development. In the present study, we
      coexpressed the human Xrcc2 and Rad51D/Rad51L3 proteins (Xrcc2 and Rad51D,
      respectively) in Escherichia coli, and purified the Xrcc2*Rad51D complex to
      homogeneity. The Xrcc2 small middle dotRad51D complex catalyzed homologous
      pairing between single-stranded and double-stranded DNA, similar to the function
      of the Xrcc3*Rad51C complex, which is another complex of the Rad51 paralogs. An
      electron microscopic analysis showed that Xrcc2*Rad51D formed a multimeric ring
      structure in the absence of DNA. In the presence of ssDNA, Xrcc2*Rad51D formed a
      filamentous structure, which is commonly observed among the human homologous
      pairing proteins, Rad51, Rad52, and Xrcc3*Rad51C.

PMID- 11834725
TI  - Brn-4 transcription factor expression targeted to the early developing mouse
      pancreas induces ectopic glucagon gene expression in insulin-producing beta
      cells.
AB  - The endocrine pancreas is comprised of beta and alpha cells producing the
      glucostatic hormones insulin and glucagon, respectively, and arises during
      development by the differentiation of stem/progenitor cells in the foregut
      programmed by the beta cell lineage-specific homeodomain protein Idx-1. Brain-4
      (Brn-4) is expressed in the pancreatic anlaga of the mouse foregut at e10 in the
      alpha cells and transactivates glucagon gene expression. We expressed Brn-4 in
      pancreatic precursors or beta cell lineage in transgenic mice by placing it under
      either Idx-1 or insulin promoter (rat insulin II promoter) control, respectively.
      Idx-1 expression occurs at developmental day e8.5, and insulin expression occurs
      at e9.5, respectively. Misexpression of Brn-4 by the Idx-1 promoter results in
      ectopic expression of the proglucagon gene in insulin-expressing pancreatic beta
      cells, whereas misexpression by rat insulin II promoter did not. The early
      developmental expression of Brn-4 appears to be a dominant regulator of the
      glucagon expressing alpha cell lineage, even in the context of the beta cell
      lineage.

PMID- 11834726
TI  - Heme redox properties of S-nitrosated hemoglobin A0 and hemoglobin S:
      implications for interactions of nitric oxide with normal and sickle red blood
      cells.
AB  - S-Nitrosated hemoglobin is remarkably stable and can be cycled between deoxy,
      oxygenated, or oxidized forms without significant loss of NO. Here we show that S
      nitrosation of adult human hemoglobin (Hb A(0)) or sickle cell Hb (Hb S) results
      in an increased ease of anaerobic heme oxidation, while anions cause redox shifts
      in the opposite direction. The negatively charged groups of the cytoplasmic
      domain of Band 3 protein also produce an allosteric effect on S-nitrosated Hb.
      Formation and deoxygenation of a SNO-Hb/Band 3 protein assembly does not in
      itself cause NO release, even in the presence of glutathione; however, this
      assembly may play a role in the migration of NO from the red blood cells to other
      targets and may be linked to Heinz body formation. Studies of the anaerobic
      oxidation of Hb S revealed an altered redox potential relative to Hb A(0) that
      favors met-Hb formation and may therefore underlie the increased rate of
      autoxidation of Hb S under aerobic conditions, the increased formation of Heinz
      bodies in sickle cells, and the decreased lifetime of red cells containing Hb S.
      A model for the interrelationships between the deoxy, oxy, and met forms of Hb
      A(0) and Hb S, and their S-nitrosated counterparts, is presented.

PMID- 11834727
TI  - Increases in free, unbound insulin-like growth factor I enhance insulin
      responsiveness in human hepatoma G2 cells in culture.
AB  - Insulin-like growth factor-binding protein (IGFBP)-1 binds to insulin-like growth
      factor (IGF)-I and -II with high affinity and has been shown to modulate IGF-I
      actions in vivo and in vitro. The synthesis of IGFBP-1 is suppressed by insulin,
      and administration of IGFBP-1 to rats results in impaired glucose metabolism. A
      synthetic peptide (bp1-01) has been shown to have a high affinity and specificity
      for human IGFBP-1 and to inhibit IGF-I binding. The current studies were
      undertaken to determine if, after incubation of bp1-01 with IGF-I.IGFBP-1
      complexes, anabolic and insulin-like effects of IGF-I could be detected in human
      hepatoma (HepG2) cell cultures and to determine the receptor subtype(s) through
      which these effects were mediated. Incubation of HepG2 cells with bp1-01 (200 nm)
      increased IGF-I-stimulated protein synthesis by 44% and glycogen synthesis by
      170% compared with stimulation by IGF-I alone. Incubation with bp1-01 also
      enhanced IGF-I-stimulated tyrosine phosphorylation of the IGF-I/insulin hybrid
      receptor and insulin receptor substrate 1. Exposure of the cells to bp1-01 alone
      enhanced glycogen synthesis and phosphorylation of IGF-I/insulin hybrid
      receptors. This was not a direct effect of bp1-01 because it did not bind to the
      receptor and did not activate tyrosine kinase activity in the presence of an anti
      IGF-I receptor antibody. The addition of bp1-01 (200 nm) plus insulin to HepG2
      cell culture medium resulted in increased tyrosine phosphorylation of the hybrid
      receptor, insulin receptor substrate 1, and the glycogen synthesis response
      compared with the effects of insulin alone. This enhancement of hybrid receptor
      phosphorylation and glycogen synthesis by bp1-01 peptide was diminished by
      preincubation with an inhibitory antibody for the alpha subunit of IGF-I receptor
      (alphaIR3). bp1-01 stimulated the hybrid receptor phosphorylation response to IGF
      I, and this effect was inhibited by prior incubation of the cells with alphaIR3.
      In conclusion, bp1-01 competes with IGF-I for binding to IGFBP-1, which leads to
      release of free IGF-I from IGF-I.IGFBP-1 complexes. This released IGF-I
      stimulates biologic actions that are mediated predominantly through the IGF
      I/insulin hybrid receptor.

PMID- 11834728
TI  - Regulation of an ERG K+ current by Src tyrosine kinase.
AB  - The human "ether-a-go-go"-related gene (HERG) K(+) channel, and its homologues
      are present in heart, neuronal tissue, some cancer cells, and the MLS-9 rat
      microglia cell line (Zhou, W., Cayabyab, F. S., Pennefather, P. S., Schlichter,
      L. C., and DeCoursey, T. E. (1998) J. Gen. Physiol. 111, 781-794). Despite its
      importance, there are few studies of ERG modulation. In this first report of
      regulation by tyrosine phosphorylation we show that MLS-9 cells express
      transcripts for r-erg1 (rat homologue of HERG) and r-erg2, and an immunoreactive
      doublet was identified using an anti-HERG antibody. The constitutive tyrosine
      phosphorylation of the ERG1 protein, detected by co-immunoprecipitation, was
      reduced by the protein-tyrosine kinase inhibitors, lavendustin A, herbimycin A,
      or genistein (but not daidzein). The whole cell ERG current was reduced by
      protein-tyrosine kinase inhibitors or the Src-selective inhibitory peptide, src40
      58, but not by a scrambled peptide. Conversely, the current was increased by the
      Src-activating peptide, srcpY, but not by an inactive analogue. Activating
      endogenous Src or transfecting constitutively active v-Src altered the voltage
      dependence and deactivation kinetics to produce more current at negative
      potentials. Co-immunoprecipitation identified an association between the channel
      protein and Src. Thus, r-ERG1 and Src tyrosine kinase appear to exist in a
      signaling complex that is well positioned to modulate this K(+) channel and
      affect its contribution to cellular functions.

PMID- 11834729
TI  - Purification and molecular characterization of cGMP-dependent protein kinase from
      Apicomplexan parasites. A novel chemotherapeutic target.
AB  - The trisubstituted pyrrole 4-[2-(4-fluorophenyl)-5-(1-methylpiperidine-4-yl)-1H
      pyrrol-3-yl]pyridine (Compound 1) inhibits the growth of Eimeria spp. both in
      vitro and in vivo. The molecular target of Compound 1 was identified as cGMP
      dependent protein kinase (PKG) using a tritiated analogue to purify a
      approximately 120-kDa protein from lysates of Eimeria tenella. This represents
      the first example of a protozoal PKG. Cloning of PKG from several Apicomplexan
      parasites has identified a parasite signature sequence of nearly 300 amino acids
      that is not found in mammalian or Drosophila PKG and which contains an
      additional, third cGMP-binding site. Nucleotide cofactor regulation of parasite
      PKG is remarkably different from mammalian enzymes. The activity of both native
      and recombinant E. tenella PKG is stimulated 1000-fold by cGMP, with significant
      cooperativity. Two isoforms of the parasite enzyme are expressed from a single
      copy gene. NH(2)-terminal sequence of the soluble isoform of PKG is consistent
      with alternative translation initiation within the open reading frame of the
      enzyme. A larger, membrane-associated isoform corresponds to the deduced full
      length protein sequence. Compound 1 is a potent inhibitor of both soluble and
      membrane-associated isoforms of native PKG, as well as recombinant enzyme, with
      an IC(50) of <1 nm.

PMID- 11834730
TI  - Insulin promotes the cell surface recruitment of the SAT2/ATA2 system A amino
      acid transporter from an endosomal compartment in skeletal muscle cells.
AB  - SAT1-3 comprise members of the recently cloned family of System A transporters
      that mediate the sodium-coupled uptake of short chain neutral amino acids, and
      their activity is regulated extensively by stimuli such as insulin, growth
      factors, and amino acid availability. In skeletal muscle, insulin stimulates
      System A activity rapidly by a presently ill-defined mechanism. Here we
      demonstrate that insulin induces an increase in the plasma membrane abundance of
      SAT2 in a phosphatidylinositol 3-kinase-dependent manner and that this increase
      is derived from an endosomal compartment that is required for the hormonal
      activation of System A. Chloroquine, an acidotropic weak base that impairs
      endosomal recycling of membrane proteins, induced a complete inhibition in the
      insulin-mediated stimulation of System A, which was associated with a loss in
      SAT2 recruitment to the plasma membrane. The failure to stimulate System A and
      recruit SAT2 to the cell surface could not be attributed to a block in insulin
      signaling, as chloroquine had no effect on the insulin-mediated phosphorylation
      of protein kinase B or glycogen synthase kinase 3 or upon insulin-stimulated
      GLUT4 translocation and glucose transport. Our data indicate strongly that
      insulin increases System A transport in L6 cells by stimulating the exocytosis of
      SAT2 carriers from a chloroquine-sensitive endosomal compartment.

PMID- 11834731
TI  - A 40-bp RNA element that mediates stabilization of vascular endothelial growth
      factor mRNA by HuR.
AB  - VEGF is a critical mediator of hypoxia-induced angiogenesis in numerous
      physiological and pathophysiological conditions. The hypoxic induction of VEGF is
      due in large part to an increase in the stability of its mRNA. We recently
      demonstrated that the stabilization of VEGF mRNA by hypoxia is dependent upon the
      RNA-binding protein HuR. This report describes the identification of a 40-bp
      functional HuR binding site in the VEGF mRNA 3'-untranslated region. This element
      can confer HuR-mediated stabilization of a heterologous gene in vitro and in
      vivo. Furthermore, the element is sufficient to confer an increase in the hypoxic
      induction of a heterologous gene. Deletion of the HuR binding site within this 40
      bp element as mapped by RNase T1 and lead footprinting uncouples a stabilizing
      sequence from a destabilizing sequence, thus providing a novel RNA-protein
      regulatory model that might be exploited to manipulate VEGF expression and
      hypoxia-induced angiogenesis.

PMID- 11834732
TI  - A remote upstream element regulates tissue-specific expression of the rat
      aggrecan gene.
AB  - The regulation of chondrogenesis and of the genes expressed as markers of
      chondrocyte differentiation is poorly understood. The hyaluronan-binding
      proteoglycan aggrecan is an essential and specific component of cartilage, but
      the aggrecan proximal promoter is expressed in an unregulated fashion in vitro.
      DNA comprising the rat aggrecan gene (83 kb including the 30-kb first intron) was
      surveyed for active elements, which would impart selective expression to the
      aggrecan promoter in transfection assays in vitro. A 4.7-kb DNA fragment (P3)
      with cell-specific enhancer activity was discovered approximately 12 kb upstream
      of the transcription start site; this active DNA fragment is position- and
      orientation-independent, and strongly stimulates aggrecan promoter expression in
      chondrocytes, while weakly suppressing transcription in fibroblasts. Most of this
      activity has been localized to P3-7, a 2.3-kb internal fragment of P3. Another
      enhancer element (A23), which is not tissue-specific, was discovered about 70 kb
      downstream of the transcription start site. Several lines of transgenic mice were
      created using combinations of these DNA elements to drive the lacZ reporter gene.
      Neither a short (900 bp) nor a long (3.7 kb) promoter alone showed detectable
      expression in 14.5-day embryos, whereas placing the P3 tissue-specific enhancer
      together with P0 gave strong expression restricted to embryonic cartilage of
      transgenic mice. The A23 downstream enhancer in conjunction with P0 did not
      confer expression. This is the first report of a gene control region which
      confers authentic tissue-specific regulation of aggrecan in vitro or in vivo and
      should greatly facilitate understanding the coordinate regulation of chondrocytic
      genes.

PMID- 11834733
TI  - Formation of inactive cAMP-saturated holoenzyme of cAMP-dependent protein kinase
      under physiological conditions.
AB  - The complex of the subunits (RIalpha, Calpha) of cAMP-dependent protein kinase I
      (cA-PKI) was much more stable (K(d) = 0.25 microm) in the presence of excess cAMP
      than previously thought. The ternary complex of C subunit with cAMP-saturated
      RIalpha or RIIalpha was devoid of catalytic activity against either peptide or
      physiological protein substrates. The ternary complex was destabilized by protein
      kinase substrate. Extrapolation from the in vitro data suggested about one-fourth
      of the C subunit to be in ternary complex in maximally cAMP-stimulated cells.
      Cells overexpressing either RIalpha or RIIalpha showed decreased CRE-dependent
      gene induction in response to maximal cAMP stimulation. This could be explained
      by enhanced ternary complex formation. Modulation of ternary complex formation by
      the level of R subunit may represent a novel way of regulating the cAMP kinase
      activity in maximally cAMP-stimulated cells.

PMID- 11834734
TI  - Concerted regulation of inhibitory activity of alpha 1-antitrypsin by the native
      strain distributed throughout the molecule.
AB  - The native forms of common globular proteins are in their most stable state but
      the native forms of plasma serpins (serine protease inhibitors) show high energy
      state interactions. The high energy state strain of alpha(1)-antitrypsin, a
      prototype serpin, is distributed throughout the whole molecule, but the strain
      that regulates the function directly appears to be localized in the region where
      the reactive site loop is inserted during complex formation with a target
      protease. To examine the functional role of the strain at other regions of
      alpha(1)-antitrypsin, we increased the stability of the molecule greatly via
      combining various stabilizing single amino acid substitutions that did not affect
      the activity individually. The results showed that a substantial increase of
      stability, over 13 kcal mol(-1), affected the inhibitory activity with a
      correlation of 11% activity loss per kcal mol(-1). Addition of an activity
      affecting single residue substitution in the loop insertion region to these very
      stable substitutions caused a further activity decrease. The results suggest that
      the native strain of alpha(1)-antitrypsin distributed throughout the molecule
      regulates the inhibitory function in a concerted manner.

PMID- 11834735
TI  - Drosophila extracellular signal-regulated kinase involves the insulin-mediated
      proliferation of Schneider cells.
AB  - The Drosophila insulin pathway is involved in the control of the proliferation
      and size of the cell. The stimulation of Schneider cells with human insulin has
      been observed to activate Drosophila extracellular signal regulated kinase
      (DERK). However, the role of DERK in the regulation of proliferation is unknown.
      In this study, we have identified a role of DERK in the proliferation of
      Drosophila Schneider cells. The inhibition of DERK activity by the overexpression
      of DMKP-3, an ERK-specific mitogen-activated protein kinase (MAPK) phosphatase,
      inhibited G(1) to S phase cell cycle progression as well as bromodeoxyuridine
      (BrdU) incorporation, which were previously increased by human insulin. However,
      DMKP-3 overexpression did not significantly reduce cell size that was also
      enlarged by insulin treatment, which suggests the specificity of the ERK pathway
      in proliferation but not for cell size. G1 to S phase cell cycle progression and
      BrdU incorporation were also reduced by catalytically inactive DMKP-3 mutant, and
      they may be acquired by the trapping of DERK into cytosol. The depletion of DERK
      or DMKP-3 by inhibitory double-stranded RNA decreased and increased BrdU
      incorporation, respectively. Thus, we propose that DERK is involved in the
      proliferation of Schneider cells via the insulin pathway.

PMID- 11834736
TI  - Flavonoid inhibition of sodium-dependent vitamin C transporter 1 (SVCT1) and
      glucose transporter isoform 2 (GLUT2), intestinal transporters for vitamin C and
      Glucose.
AB  - Vitamin C and flavonoids, polyphenols with uncertain function, are abundant in
      fruits and vegetables. We postulated that flavonoids have a novel regulatory
      action of delaying or inhibiting absorption of vitamin C and glucose, which are
      structurally similar. From six structural classes of flavonoids, at least 12
      compounds were chosen for studies. We investigated the effects of selected
      flavonoids on the intestinal vitamin C transporter SVCT1(h) by transfecting and
      overexpressing SVCT1(h) in Chinese hamster ovary cells. Flavonoids reversibly
      inhibited vitamin C transport in transfected cells with IC(50) values of 10-50
      microm, concentrations expected to have physiologic consequences. The most potent
      inhibitor class was flavonols, of which quercetin is most abundant in foods.
      Because Chinese hamster ovary cells have endogenous vitamin C transport, we
      expressed SVCT1(h) in Xenopus laevis oocytes to study the mechanism of transport
      inhibition. Quercetin was a reversible and non-competitive inhibitor of ascorbate
      transport; K(i) 17.8 microm. Quercetin was a potent non-competitive inhibitor of
      GLUT2 expressed in Xenopus oocytes; K(i) 22.8 microm. When diabetic rats were
      administered glucose with quercetin, hyperglycemia was significantly decreased
      compared with administration of glucose alone. Quercetin also significantly
      decreased ascorbate absorption in normal rats given ascorbate plus quercetin
      compared with rats given ascorbate alone. Quercetin was a specific transport
      inhibitor, because it did not inhibit intestinal sugar transporters GLUT5 and
      SGLT1 that were injected and expressed in Xenopus oocytes. Quercetin inhibited
      but was not transported by SVCT1(h). Considered together, these data show that
      flavonoids modulate vitamin C and glucose transport by their respective
      intestinal transporters and suggest a new function for flavonoids.

PMID- 11834737
TI  - A central dinucleotide within vitamin D response elements modulates DNA binding
      and transactivation by the vitamin D receptor in cellular response to natural and
      synthetic ligands.
AB  - There is considerable divergence in the sequences of steroid receptor response
      elements, including the vitamin D response elements (VDREs). Two major VDRE
      containing and thus 1,25-dihydroxyvitamin D(3) (1,25-(OH)(2)D(3))-regulated genes
      are the two non-collagenous, osteoblast-derived bone matrix proteins osteocalcin
      and osteopontin. We observed a stronger induction of osteopontin than osteocalcin
      mRNA expression by 1,25-(OH)(2)D(3). Subsequently, we have shown that vitamin D
      receptor/retinoid X receptor alpha (VDR/RXRalpha) heterodimers bind more tightly
      to the osteopontin VDRE than to the osteocalcin VDRE. Studies using point mutants
      revealed that the internal dinucleotide at positions 3 and 4 of the proximal
      steroid half-element are most important for modulating the strength of receptor
      binding. In addition, studies with VDRE-driven luciferase reporter gene
      constructs revealed that the central dinucleotide influences the transactivation
      potential of VDR/RXRalpha with the same order of magnitude as that observed in
      the DNA binding studies. The synthetic vitamin D analog KH1060 is a more potent
      stimulator of transcription and inducer of VDRE binding of VDR/RXR in the
      presence of nuclear factors isolated from ROS 17/2.8 osteoblast-like cells than
      the natural ligand 1,25-(OH)(2)D(3). Interestingly, however, KH1060 is comparable
      or even less potent than 1,25-(OH)(2)D(3) in stimulating VDRE binding of in vitro
      synthesized VDR/RXRalpha. Thus, the extent of 1,25-(OH)(2)D(3)- and KH1060
      dependent binding of VDR/RXRalpha is specified by a central dinucleotide in the
      VDRE, and the ligand-induced effects on DNA binding are in part controlled by the
      cellular context of nuclear proteins.

PMID- 11834738
TI  - Reductive cleavage of S-adenosylmethionine by biotin synthase from Escherichia
      coli.
AB  - Biotin synthase (BioB) catalyzes the insertion of a sulfur atom between the C6
      and C9 carbons of dethiobiotin. Reconstituted BioB from Escherichia coli contains
      a [4Fe-4S](2+/1+) cluster thought to be involved in the reduction and cleavage of
      S-adenosylmethionine (AdoMet), generating methionine and the reactive 5'
      deoxyadenosyl radical responsible for dethiobiotin H-abstraction. Using EPR and
      Mossbauer spectroscopy as well as methionine quantitation we demonstrate that the
      reduced S = 1/2 [4Fe-4S](1+) cluster is indeed capable of injecting one electron
      into AdoMet, generating one equivalent of both methionine and S = 0 [4Fe-4S](2+)
      cluster. Dethiobiotin is not required for the reaction. Using site-directed
      mutagenesis we show also that, among the eight cysteines of BioB, only three (Cys
      53, Cys-57, Cys-60) are essential for AdoMet reductive cleavage, suggesting that
      these cysteines are involved in chelation of the [4Fe-4S](2+/1+) cluster.

PMID- 11834739
TI  - Separate functions for the two modules of the membrane-proximal cytokine binding
      domain of glycoprotein 190, the leukemia inhibitory factor low affinity receptor,
      in ligand binding and receptor activation.
AB  - The receptor for the cytokine leukemia inhibitory factor (LIF) associates the low
      affinity binding component gp190 and the high affinity converter gp130. Both are
      members of the hematopoietic receptors family characterized by the cytokine
      receptor homology (CRH) domain, which consists of two barrel-like modules of
      around 100 amino acids each. The gp190 is among the very few members of this
      large family to contain two CRH domains. The membrane-distal one (herein called
      D1) is followed by an immunoglobulin-like domain, a membrane-proximal CRH domain
      called D2, and three type III fibronectin-like repeats. A minimal D1IgD2 fragment
      is required for binding LIF. By using transmembrane forms of deletion mutants in
      gp190 ectodomain, we demonstrated that removal of D1 led to spontaneous
      activation of the receptor and that this property was devoted to a peptidic
      sequence localized within the last 42 amino acids of the carboxyl-terminal module
      of D2. By using soluble forms of deletion mutants made by progressive truncations
      from the end of the D1IgD2 fragment, we demonstrated that the carboxyl-terminal
      module of D2 was dispensable for LIF binding and that the correct conformation of
      the D1Ig fragment required a full amino-terminal module of D2. Therefore, the two
      constitutive modules of the membrane-proximal CRH domain D2 of gp190 fulfill two
      distinct roles in gp190 function, i.e. in stabilizing the conformation of gp190
      allowing LIF binding and in activating the receptor.

PMID- 11834740
TI  - Wnt signaling controls the phosphorylation status of beta-catenin.
AB  - At the heart of the canonical Wnt signaling cascade, adenomatous polyposis coli
      (APC), axin, and GSK3 constitute the so-called destruction complex, which
      controls the stability of beta-catenin. It is generally believed that four
      conserved Ser/Thr residues in the N terminus of beta-catenin are the pivotal
      targets for the constitutively active serine kinase GSK3. In cells that do not
      receive Wnt signals, glycogen synthase kinase (GSK) is presumed to phosphorylate
      beta-catenin, thus marking the latter for proteasomal degradation. Wnt signaling
      inhibits GSK3 activity. As a consequence, beta-catenin would no longer be
      phosphorylated and accumulate to form nuclear complexes with TCF/LEF factors.
      Although mutations in or near the N-terminal Ser/Thr residues stabilize beta
      catenin in several types of cancer, the hypothesis that Wnt signaling controls
      phosphorylation of these residues remains unproven. We have generated a
      monoclonal antibody that recognizes an epitope containing two of the four
      residues when both are not phosphorylated. The epitope is generated upon Wnt
      signaling as well as upon pharmacological inhibition of GSK3 by lithium,
      providing formal proof for the regulated phosphorylation of the Ser/Thr residues
      of beta-catenin by Wnt signaling. Immunohistochemical analysis of mouse embryos
      utilizing the antibody visualizes sites that transduce Wnt signals through the
      canonical Wnt cascade.

PMID- 11834741
TI  - Recognition by tryptophanyl-tRNA synthetases of discriminator base on tRNATrp
      from three biological domains.
AB  - To study the recognition by tryptophanyl-tRNA synthetase (TrpRS) of tRNA(Trp)
      discriminator base, mutations were introduced into the discriminator base of
      Bacillus subtilis, Archeoglobus fulgidus, and bovine tRNA(Trp), representing the
      three biological domains. When B. subtilis, A. fulgidus, and human TrpRS were
      used to acylate these tRNA(Trp), two distinct preference profiles regarding the
      discriminator base of different tRNA(Trp) substrates were found: G>A>U>C for B.
      subtilis TrpRS, and A>C>U>G for A. fulgidus and human TrpRS. The preference for
      G73 in tRNA(Trp) by bacterial TrpRS is much stronger than the modest preferences
      for A73 by the archaeal and eukaryotic TrpRS. Cross-species reactivities between
      TrpRS and tRNA(Trp) from the three domains were in accordance with the view that
      the evolutionary position of archaea is intermediate between those of eukarya and
      bacteria. NMR spectroscopy revealed that mutation of A73 to G73 in bovine
      tRNA(Trp) elicited a conformational alteration in the G1-C72 base pair. Mutation
      of G1-C72 to A1-U72 or disruption of the G1-C72 base pair also caused reduction
      of Trp-tRNA(Trp) formation. These observations identify a tRNA(Trp) structural
      region near the end of acceptor stem comprising A73 and G1-C72 as a crucial
      domain required for effective recognition by human TrpRS.

PMID- 11834742
TI  - Functional characterization of three novel tissue-specific anion exchangers
      SLC26A7, -A8, and -A9.
AB  - A second distinct family of anion exchangers, SLC26, in addition to the classical
      SLC4 (or anion exchanger) family, has recently been delineated. Particular
      interest in this gene family is stimulated by the fact that the SLC26A2, SLC26A3,
      and SLC26A4 genes have been recognized as the disease genes mutated in
      diastrophic dysplasia, congenital chloride diarrhea, and Pendred syndrome,
      respectively. We report the expansion of the SLC26 gene family by characterizing
      three novel tissue-specific members, named SLC26A7, SLC26A8, and SLC26A9, on
      chromosomes 8, 6, and 1, respectively. The SLC26A7-A9 proteins are structurally
      very similar at the amino acid level to the previous family members and show
      tissue-specific expression in kidney, testis, and lung, respectively. More
      detailed characterization by immunohistochemistry and/or in situ hybridization
      localized SLC26A7 to distal segments of nephrons, SLC26A8 to developing
      spermatocytes, and SLC26A9 to the lumenal side of the bronchiolar and alveolar
      epithelium of lung. Expression of SLC26A7-A9 proteins in Xenopus oocytes
      demonstrated chloride, sulfate, and oxalate transport activity, suggesting that
      they encode functional anion exchangers. The functional characterization of the
      novel tissue-specific members may provide new insights to anion transport
      physiology in different parts of body.

PMID- 11834743
TI  - Dissociation time from DNA determines transcriptional function in a STAT1 linker
      mutant.
AB  - The STAT1 transcription factor is organized into several highly conserved
      domains, each of which has been assigned a function with the exception of the
      linker domain. We previously characterized a mutant in the linker domain of STAT1
      that gave normal DNA binding using a standard probe in an electrophoretic
      mobility assay but failed to activate transcription in response to interferon
      gamma. We now report the mechanistic basis for the inactivity of this
      STAT1(K544A/E545A) mutant. Rather than failing to attract transcriptional
      coactivators, the STAT1(K544A/E545A) mutant has a subtle biophysical defect,
      which prevents accumulation of the activated protein on chromatin in vivo: the
      mutant has comparable K(d) with greatly increased k(off) for DNA binding. The
      increase in both on-rate and off-rate of DNA binding results in a substantially
      reduced residence time of STAT1(K544A/E545A) on STAT binding sites. We find a
      similar correlation between off-rate and transcriptional potency for
      STAT1(N460A), which bears a mutation in the DNA binding domain. These results
      yield insight into the rate of complex assembly involving STAT1 that leads to
      transcriptional stimulation.

PMID- 11834744
TI  - Charcot-Leyden crystal protein (galectin-10) is not a dual function galectin with
      lysophospholipase activity but binds a lysophospholipase inhibitor in a novel
      structural fashion.
AB  - Charcot-Leyden crystal (CLC) protein, initially reported to possess weak
      lysophospholipase activity, is still considered to be the eosinophil's
      lysophospholipase, but it shows no sequence similarities to any known
      lysophospholipases. In contrast, CLC protein has moderate sequence similarity,
      conserved genomic organization, and near structural identity to members of the
      galectin superfamily, and it has been designated galectin-10. To definitively
      determine whether or not CLC protein is a lysophospholipase, we reassessed its
      enzymatic activity in peripheral blood eosinophils and an eosinophil myelocyte
      cell line (AML14.3D10). Antibody affinity chromatography was used to fully
      deplete CLC protein from eosinophil lysates. The CLC-depleted lysates retained
      their full lysophospholipase activity, and this activity could be blocked by
      sulfhydryl group-reactive inhibitors, N-ethylmaleimide and p
      chloromercuribenzenesulfonate, previously reported to inhibit the eosinophil
      enzyme. In contrast, the affinity-purified CLC protein lacked significant
      lysophospholipase activity. X-ray crystallographic structures of CLC protein in
      complex with the inhibitors showed that p-chloromercuribenzenesulfonate bound CLC
      protein via disulfide bonds with Cys(29) and with Cys(57) near the carbohydrate
      recognition domain (CRD), whereas N-ethylmaleimide bound to the galectin-10 CRD
      via ring stacking interactions with Trp(72), in a manner highly analogous to
      mannose binding to this CRD. Antibodies to rat pancreatic lysophospholipase
      identified a protein in eosinophil and AML14.3D10 cell lysates, comparable in
      size with human pancreatic lysophospholipase, which co-purifies in small
      quantities with CLC protein. Ligand blotting of human and murine eosinophil
      lysates with CLC protein as probe showed that it binds proteins also recognized
      by antibodies to pancreatic lysophospholipase. Our results definitively show that
      CLC protein is not one of the eosinophil's lysophospholipases but that it does
      interact with eosinophil lysophospholipases and known inhibitors of this
      lipolytic activity.

PMID- 11834745
TI  - Peroxynitrite-induced nitration of tyrosine hydroxylase: identification of
      tyrosines 423, 428, and 432 as sites of modification by matrix-assisted laser
      desorption ionization time-of-flight mass spectrometry and tyrosine-scanning
      mutagenesis.
AB  - Tyrosine hydroxylase (TH), the initial and rate-limiting enzyme in the
      biosynthesis of the neurotransmitter dopamine, is inactivated by peroxynitrite.
      The sites of peroxynitrite-induced tyrosine nitration in TH have been identified
      by matrix-assisted laser desorption time-of-flight mass spectrometry and tyrosine
      scanning mutagenesis. V8 proteolytic fragments of nitrated TH were analyzed by
      matrix-assisted laser desorption time-of-flight mass spectrometry. A peptide of
      3135.4 daltons, corresponding to residues V410-E436 of TH, showed peroxynitrite
      induced mass shifts of +45, +90, and +135 daltons, reflecting nitration of one,
      two, or three tyrosines, respectively. These modifications were not evident in
      untreated TH. The tyrosine residues (positions 423, 428, and 432) within this
      peptide were mutated to phenylalanine to confirm the site(s) of nitration and
      assess the effects of mutation on TH activity. Single mutants expressed wild-type
      levels of TH catalytic activity and were inactivated by peroxynitrite while
      showing reduced (30-60%) levels of nitration. The double mutants Y423F,Y428F,
      Y423F,Y432F, and Y428F,Y432F showed trace amounts of tyrosine nitration (7-30% of
      control) after exposure to peroxynitrite, and the triple mutant Y423F,Y428F,Y432F
      was not a substrate for nitration, yet peroxynitrite significantly reduced the
      activity of each. When all tyrosine mutants were probed with PEO-maleimide
      activated biotin, a thiol-reactive reagent that specifically labels reduced
      cysteine residues in proteins, it was evident that peroxynitrite resulted in
      cysteine oxidation. These studies identify residues Tyr(423), Tyr(428), and
      Tyr(432) as the sites of peroxynitrite-induced nitration in TH. No single
      tyrosine residue appears to be critical for TH catalytic function, and tyrosine
      nitration is neither necessary nor sufficient for peroxynitrite-induced
      inactivation. The loss of TH catalytic activity caused by peroxynitrite is
      associated instead with oxidation of cysteine residues.

PMID- 11834746
TI  - Redox effector factor-1 regulates the activity of thyroid transcription factor 1
      by controlling the redox state of the N transcriptional activation domain.
AB  - Thyroid transcription factor 1 (TTF-1) is a homeodomain-containing
      transcriptional regulator responsible for the activation of thyroid- and lung
      specific genes. It has been demonstrated that its DNA binding activity is redox
      regulated in vitro through the formation of dimers and oligomeric species. In
      this paper, we demonstrate that the redox regulation mainly involves a Cys
      residue (Cys(87)), which resides out of the DNA binding domain, belonging to the
      N-transactivation domain. In fact, the oxidized form of a truncated TTF-1
      (containing the N-transactivation domain and the DNA-binding domain, here called
      TTF-1N-HD) looses specific DNA binding activity. Since most of the oxidized TTF
      1N-HD is in a monomeric form, these data indicate that the redox state of Cys(87)
      may control the DNA-binding function of the homeodomain, suggesting that Cys(87)
      could play an important role in determining the correct folding of the
      homeodomain. By using gel retardation and transient transfection assays, we
      demonstrate that the redox effector factor-1 (Ref-1) mediates the redox effects
      on TTF-1N-HD binding and that it is able to modulate the TTF-1 transcriptional
      activity. Glutathione S-transferase pull-down experiments demonstrate the
      occurrence of interaction between Ref-1 and TTF-1N-HD. Having previously
      demonstrated that Ref-1 is able to modulate the transcriptional activity of
      another thyroid-specific transcription factor (Pax-8), our data suggest that Ref
      1 plays a central role in the regulation of thyroid cells.

PMID- 11834747
TI  - Two deaths and two lessons: is it time to review the structure and function of
      research ethics committees?

PMID- 11834748
TI  - The hexamethonium asthma study and the death of a normal volunteer in research.

PMID- 11834749
TI  - White coat ceremonies: a second opinion.
AB  - A "white coat" ceremony functions as a rite of passage for students entering
      medical school. This comment provides a second option in response to the earlier,
      more enthusiastic, discussion of the ceremony by Raanan Gillon. While these
      ceremonies may serve important sociological functions, they raise three serious
      problems: whether the professional oath or "affirmation of professional
      commitment" taken in this setting has any legitimacy, how a sponsor of such a
      ceremony would know which oath or affirmation to administer, and what the moral
      implications of this "bonding process" are. I argue that the initiation oath is
      morally meaningless if students are not aware of its content in advance, that
      different students ought to commit to different oaths, and that bonding of
      students to the medical profession necessarily separates them from identification
      with lay people who will be their patients.

PMID- 11834752
TI  - Prophylactic interventions on children: balancing human rights with public
      health.
AB  - Bioethics committees have issued guidelines that medical interventions should be
      permissible only in cases of clinically verifiable disease, deformity, or injury.
      Furthermore, once the existence of one or more of these requirements has been
      proven, the proposed therapeutic procedure must reasonably be expected to result
      in a net benefit to the patient. As an exception to this rule, some prophylactic
      interventions might be performed on individuals "in their best interests" or with
      the aim of averting an urgent and potentially calamitous public health danger. In
      order to invoke these exceptions, a stringent set of criteria must first be
      satisfied. Additionally, where the proposed prophylactic intervention is intended
      for children, who are unlikely to be able to provide a meaningfully informed
      consent, a heightened scrutiny of any such measures is required. We argue that
      children should not be subjected to prophylactic interventions "in their best
      interests" or for public health reasons when there exist effective and
      conservative alternative interventions, such as behavioural modification, that
      individuals could employ as competent adolescents or adults to avoid adverse
      health outcomes. Applying these criteria, we consider the specific examples of
      prophylactic mastectomy, immunisations, cosmetic ear surgery, and circumcision.

PMID- 11834753
TI  - On the theory of individual health.
AB  - On top of elaborate methods and approaches in research, diagnostics, and therapy,
      medicine is in need of a theory of its own thought and action; without
      theoretical reflection and referentiality, action becomes blind (and thus costly)
      and thought takes on a monotonous and circular character. Take the concept of
      health. The field of medicine, more and more taking its cues from evidence-based
      medicine (EBM), is onesidedly oriented to concepts of health which are based on
      notions of standard values for large populations or-in the shadow of the genome
      project-see health as the outcome of an intact genome, often turning a blind eye
      to the individual aspects of health. With an eye in particular to Friedrich
      Nietzsche's philosophy, the present paper looks into some continental European
      theories of individual health, seeking to determine to what extent they can
      contribute to reducing medicine's theory deficit and what consequences this may
      have for research, diagnostics, and therapy.

PMID- 11834754
TI  - Rationing, randomizing, and researching in health care provision.
AB  - In this paper the need for valid evidence of the cost-effectiveness of treatments
      that have not been properly evaluated, yet are already available, albeit in short
      supply, are examined. Such treatments cannot be withdrawn, pending proper
      evaluation, nor can they be made more widely available until they have been shown
      to be cost-effective. As a solution to this impasse the argument put forward
      recently by Toroyan et al is discussed. They say that randomised controlled
      trials of such resources could be done but only if resources are randomly
      allocated independently of a research context. Relevant outcome data could then
      be collected for research, given this opportunity. (There are already a few
      investigators who have turned limited resources, mostly health service provision,
      to their advantage in this way.) We agree. We disagree with Toroyan et al on a
      number of points. First, they claim that no ethical issue relating to equipoise
      arises. We disagree and this disagreement depends on our showing that equipoise
      should be maintained in a relationship that they do not consider. Secondly, they
      say that consent to data collection is always needed. Again we disagree. Thirdly,
      they claim that the previous two issues are the only possible ethical issues that
      could arise. We argue, instead, that there is a further conflict of interests
      that has ethical import.

PMID- 11834755
TI  - Who is my brother's keeper?
AB  - Clinical and research practices designed by developed countries are often
      implemented in host nations of the Third World. In recent years, a number of
      papers have presented a diversity of arguments to justify these practices which
      include the defence of research with placebos even though best proven treatments
      exist; the distribution of drugs unapproved in their country of origin;
      withholding of existing therapy in order to observe the natural course of
      infection and disease; redefinition of equipoise to a more bland version, and
      denial of post-trial benefits to research subjects. These practices have all been
      prohibited in developed, sponsoring countries, even though they invariably have
      pockets of poverty where conditions comparable to the Third World prevail.
      Furthermore, the latest update of the Declaration of Helsinki clearly decries
      double ethical standards in research protocols. Under these circumstances, it
      does not seem appropriate that First World scholars should propose and defend
      research and clinical practices with less stringent ethical standards than those
      mandatory in their own countries. Recent years have witnessed frequent reports of
      less stringent ethical standards being applied to both clinical and research
      medical practices, for the most part in the field of drug trials and drug
      marketing, initiated by developed countries in poorer nations. Still more
      unsettling, a number of articles have endorsed the policy of employing ethical
      norms in these host countries, which would be unacceptable to both the
      legislations and the moral standards of the sponsor nations. Also, these
      reformulations often contravene the Declaration of Helsinki or one of its
      updates. This paper is not so much concerned with the actual practices, which
      have been subjected to frequent scrutiny and publicly decried when gross
      misconduct occurred. Rather, my concern relates to the approval and support such
      practices have found in the literature on bioethics from authors who might be
      expected to use their energy and scholarship to explore and endorse the
      universalisability of ethics rather than to develop ad hoc arguments that would
      allow exceptions and variations from accepted moral standards. To this purpose,
      issue will be taken with arguments in three fields: medical and pharmaceutical
      practices, research strategies, and local application of research results.

PMID- 11834756
TI  - Arguments at cross-purposes: moral epistemology and medical ethics.
AB  - Different beliefs about the nature and justification of bioethics may reflect
      different assumptions in moral epistemology. Two alternative views (put forward
      by David Seedhouse and Michael H Kottow) are analysed and some speculative
      conclusions formed. The foundational questions raised here are by no means
      settled and deserve further attention.

PMID- 11834757
TI  - Ethical considerations for services offering one-to-one guidance for primary care
      practitioners interested in research.
AB  - Initiatives which offer support to primary care practitioners interested in
      research have become widespread in the UK. There has been little debate, however,
      about the ethical issues involved in such interactions with practitioners.
      Established codes of practice and analyses of the institutional and strategic
      contexts have been used to inform this discussion. The paper concludes with a
      recommendation that more explicit quasi-contractual relationships should be
      negotiated between those offering and those seeking help.

PMID- 11834758
TI  - Is there an advocate in the house? The role of health care professionals in
      patient advocacy.
AB  - It remains unclear what patient advocacy actually entails and what values it
      ought to embody. It will be useful to ascertain whether advocacy means supporting
      any decision the patient makes, or if the advocate can claim to represent the
      patient by asserting well-intentioned paternalistic claims on the patient's
      behalf. This is especially significant because the position of advocate brings
      with it certain privileges on the basis of of presumed insight into patient
      perceived interests, namely, entitlement to take part in clinical decision making
      and increased professional standing. Three issues related to patient advocacy
      will be explored: are patient advocates necessary; what does advocacy entail, and
      who ought to represent patients in this way-arguments for and against prospective
      candidates will also be covered. The paper considers whether advocates are
      necessary since not only can they be dangerously paternalistic, but the salutary
      values advocacy embodies are already part of good professional health care.

PMID- 11834759
TI  - It doesn't cost anything just to ask, does it? The ethics of questionnaire-based
      research.
AB  - Patient-based outcome measures are increasingly important in health care
      evaluations, often through the use of paper-based questionnaires. The likely
      impact of questionnaires upon patients is not often considered and therefore, the
      balance of benefit and harm not fully explored. Harms that might accrue for
      research staff are even less frequently considered. This paper describes the use
      of postal questionnaires within a study of breast disease management in primary
      care. Questionnaire responses are used to describe the nature of discomfort or
      harms that may occur in such studies. Ethical issues raised by the harms are
      discussed in relation to the benefits of the study. Practical suggestions for
      reducing harm to patients are proposed. A secondary consideration, discomfort to
      the researcher, is also identified and suggestions made to reduce its effect.
      Finally, the role of research questionnaires as a study intervention is
      discussed.

PMID- 11834760
TI  - Patients' perceptions of information provided in clinical trials.
AB  - BACKGROUND: According to the Declaration of Helsinki, patients who take part in a
      clinical trial must be adequately informed about the trial's aims, methods,
      expected benefits, and potential risks. The declaration does not, however,
      elaborate on what "adequately informed" might amount to, in practice. Medical
      researchers and Local Research Ethics Committees attempt to ensure that the
      information which potential participants are given is pitched at an appropriate
      level, but few studies have considered whether the patients who take part in such
      trials feel they have been given adequate information, or whether they feel able
      to understand that information. OBJECTIVES: To explore trial participants' views
      (i) on the amount of information provided, and (ii) of their own understanding of
      that information. DESIGN: Structured interviews of patients participating in
      clinical trials for the treatment of chronic medical condition. FINDINGS:
      Patients generally felt they were given an appropriate amount of information, and
      that they were able to understand all or most of it. They felt they were given
      adequate time to ask questions before agreeing to take part. In comparison with
      treatment given out with the research setting, patients generally felt they
      received more information when participating in a clinical trial. CONCLUSIONS:
      Researchers sometimes complain that patients are given too much information
      during clinical trials, and have limited understanding of that information. The
      present study shows that this perception is not necessarily shared by patients.
      More research is needed in this area, particularly to gauge whether patient
      understanding is indeed accurate.

PMID- 11834761
TI  - Operation Lifeline Sudan.
AB  - The provision of aid in war zones can be fraught with political difficulties and
      may itself foster inequalities, as it is rare to be allowed access to civilians
      on both sides of a conflict. Over the past decade, a United Nations (UN) brokered
      agreement has allowed Operation Lifeline Sudan (OLS), a UN "umbrella"
      organisation, to provide the diplomatic cover and operational support to allow
      long term humanitarian and emergency food aid to both the government and the
      rebel sides in the long-running south Sudanese civil war. Over the years, the
      destruction of infrastructure in the country has meant that the provision of
      basic health care has been seriously hampered. Operation Lifeline Sudan has
      coordinated the work of most of the non-governmental organisations (NGOs),
      working in this part of Africa. Each NGO has had responsibility for a particular
      area of the country and has worked closely with the local Sudanese authorities on
      either side of the conflict, conforming to strict codes of conduct or "ground
      rules", based on neutrality. Operation Lifeline Sudan has provided an air-bridge
      for emergency relief supplies in regions where road access is impossible, either
      because of landmines, or simply because the roads do not exist. The war
      continues, however, and the underlying causes of war-economic exploitation,
      marginalisation of communities, lack of political representation, and systematic
      violence and abuse remain unsolved. The warring factions have brought some OLS
      operations in south Sudan to a standstill recently, for certain political reasons
      that could have compromised the neutrality of the OLS-coordinated humanitarian
      aid schemes. It would appear that the only resolution to the country's problems
      are external political pressure to get the respective combatants to negotiate
      and, less probably, an undertaking by countries of the developed world not to
      continue to supply arms. Nevertheless, OLS may serve as a model for how medical
      aid can be delivered in an even-handed way to the populations of countries where
      there is civil war, irrespective of where they may live.

PMID- 11834762
TI  - Attitudes to physician and family assisted suicide: results from a study of
      public attitudes in Britain.

PMID- 11834763
TI  - Ethics briefings.

PMID- 11834767
TI  - Osteopontin--a molecule for all seasons.

PMID- 11834768
TI  - Size at birth, adult intestinal calcium absorption and 1,25(OH)(2) vitamin D.
AB  - BACKGROUND: Adult bone mineral status is modified by early environmental
      influences, but the mechanism of this phenomenon is unknown. Intestinal calcium
      absorption and vitamin D metabolism are integrally involved in bone metabolism
      and may be programmed during early life. AIM: To examine the early-life
      influences on calcium absorption and its control in 322 post-menopausal female
      twins. METHODS: Intestinal calcium absorption was assessed by the stable
      strontium (Sr) method. Serum PTH, 25(OH) and 1,25(OH)(2) vitamin D were measured
      and recalled birth weight recorded. RESULTS: Fractional intestinal Sr absorption
      (alpha Sr) was correlated with serum 1,25(OH)(2) vitamin D (p<0.001), but not
      with 25(OH) vitamin D. Birth weight was inversely associated with serum
      1,25(OH)(2) vitamin D (p=0.04), the association being independent of serum
      calcium, phosphate, creatinine and PTH. Birth weight was inversely correlated
      with alpha Sr (p=0.03), this association being independent of age, season,
      customary calcium intake and serum 25(OH) vitamin D; however, when serum
      1,25(OH)(2) vitamin D was added into the model, the association became non
      significant, suggesting that the association was partially mediated via serum
      1,25(OH)(2) vitamin D. DISCUSSION: We found a significant inverse association
      between birth weight and intestinal calcium absorption that is partially
      explained by an association between serum 1,25(OH)(2) vitamin D and birth weight.
      This suggests a mechanism whereby the intra-uterine environment might affect
      adult skeletal status.

PMID- 11834769
TI  - Costs of aspirin and statins in general practice.
AB  - BACKGROUND: Aspirin and statins are the two drugs most commonly indicated for
      secondary prevention of atherosclerotic disease in the UK. Statin treatment,
      which is more expensive, is under-prescribed. AIM: To assess the expenditure in
      Greater Manchester general practices on aspirin and statins. DESIGN: Survey of
      general practice records. METHODS: Practice registers were searched for patients
      receiving regular prescriptions for aspirin. For each patient, the next patient
      of the same sex, aged within +/- 5 years, not on aspirin, acted as a control.
      Details of all medications were recorded. In a sub-study, records of 100 patients
      on aspirin were studied to determine indications for aspirin prescription.
      RESULTS: There were 1003 (511 men, 492 women) in each group; mean age was 70
      years in both groups. In the sub-study, 79% of patients received aspirin for
      established vascular disease, 9% for hypertension, 5% for diabetes mellitus, 5%
      for unknown reasons and 2% for arthritis. Of the patients on aspirin, 67%
      received dispersible aspirin 75 mg/day. The rest were on higher doses (10%) or on
      more expensive preparations (22%), costing up to 22.4 p/day. The mean daily cost
      of aspirin was 1.7p. Dyspepsia treatment was received by 266 patients and 194
      controls (p<0.001). There was a wide range of dyspepsia medications (10
      306p/day), averaging in the groups as a whole 15.5p/day in patients and 12.5p/day
      in controls. Of the patients on aspirin, 28% received statins, compared to 4% of
      controls. Mean daily expenditure on statins in patients was 23.4p. CONCLUSION:
      Assuming the difference in the use of medication for dyspepsia between patients
      and controls was due to aspirin, the full cost of aspirin treatment was 4.7p/day.
      Statins were probably under-prescribed in aspirin-takers, many of whom would have
      been at high CHD risk.

PMID- 11834770
TI  - The effect of folic acid supplementation on plasma homocysteine in an elderly
      population.
AB  - BACKGROUND: Increased plasma homocysteine is associated with coronary artery
      disease, peripheral vascular disease and venous thrombosis. Folic acid is the
      most effective therapy for reducing homocysteine levels. The lowest effective
      supplement of folic acid is not known, particularly for the elderly who have the
      highest prevalence of these conditions. AIM: To explore the effects of daily
      supplements of 0, 50, 100, 200, 400 and 600 microg folic acid on plasma
      homocysteine in an elderly population. DESIGN: Randomized double-blind placebo
      controlled trial. METHODS: Participants (n=368) aged 65-75 years were randomly
      allocated to receive one of the treatments for 6 weeks. Plasma homocysteine was
      recorded after 3 weeks and 6 weeks of supplementation. RESULTS: Only the 400
      microg and 600 microg groups had significantly lower homocysteine levels compared
      to placebo (p=0.038 and p<0.001, respectively). Using multiple linear regression
      and each individual's total folic acid intake (diet plus supplement), a total
      daily folic acid intake of 926 microg per day would be required to ensure that
      95% of the elderly population would be without cardiovascular risk from folate
      deficiency. DISCUSSION: A daily folic acid intake of 926 microg is unlikely to be
      achieved by diet alone. Individual supplementation or fortification of food with
      folic acid will be required to reach this target.

PMID- 11834771
TI  - Acute renal failure and metabolic disturbances in the short bowel syndrome.
AB  - BACKGROUND: Short bowel syndrome (SBS) describes a malabsorptive state caused by
      extensive loss of small intestinal length. AIM: To improve understanding of the
      metabolic complications of SBS. DESIGN: Observational study of five patients with
      SBS who presented with acute renal failure. RESULTS: Acute renal failure in our
      patients was predominantly due to salt and fluid depletion, and sepsis.
      Electrolyte imbalance was a major cause of morbidity. Metabolic acidosis was seen
      in three patients, and may arise from excessive gastrointestinal bicarbonate
      loss, compounded by impaired renal homeostasis. Our patients also manifested
      disturbances of calcium and magnesium homeostasis. DISCUSSION: Patients with SBS
      are at high risk of renal failure. Prevention of this complication requires close
      monitoring and the maintenance of sodium homeostasis through increased intake and
      measures to reduce loss (e.g. anti-motility agents and large bowel re
      anastomosis), and calcium, magnesium and vitamin D supplementation.

PMID- 11834772
TI  - Diabetic nephropathy: how effective is treatment in clinical practice?
AB  - BACKGROUND: Diabetic nephropathy is the most common cause of end-stage renal
      failure in patients starting dialysis in the developed world. In clinical trials,
      interventions, particularly blood pressure control, have achieved major
      reductions in the rate of decline in renal function. AIM: To investigate whether
      results from clinical trials can be achieved in routine clinical practice.
      DESIGN: Observational study of 170 consecutive patients referred to a combined
      diabetic-renal clinic over a 10 year period. METHODS: We collected demographic
      and laboratory data from the electronic patient record. RESULTS: Median serum
      creatinine at referral was 170 micromol/l and was >350 micromol/l in 26% of
      patients. Mean blood pressure (BP) was 159/85. The publication of guidelines by
      the Scottish Intercollegiate Guidelines Network in 1997, recommending more active
      intervention and earlier referral, had no impact on referral BP and creatinine.
      In the 125 patients with at least 1 year follow-up, significant improvements in
      BP, albuminuria, HbA(1c) and serum cholesterol were seen. In the 63 patients
      followed up for 3 years (median creatinine 120 micromol/l), the median rate of
      decline in renal function slowed from 0.52 ml/min/month (first year) to 0.27
      ml/min/month (third year) (p=0.003), nearly doubling the time to end-stage renal
      failure. DISCUSSION: Patients referred early to a combined diabetic-renal clinic
      benefited by slowing in the rate of decline of renal function. A challenging but
      achievable standard for audit would be to reduce the rate of progression to <0.25
      ml/min/month in 70% of patients with diabetic nephropathy presenting with a serum
      creatinine <150 micromol/l.

PMID- 11834773
TI  - The bridge trembles.

PMID- 11834774
TI  - Can beta blockers be safely initiated at home in patients with heart failure?

PMID- 11834775
TI  - The right patient in the right place at the right time.

PMID- 11834776
TI  - Weight gain and treatment for thyrotoxicosis.

PMID- 11834777
TI  - Acute myocardial infarction following bupropion (Zyban).

PMID- 11834778
TI  - An unexpected light.

PMID- 11834779
TI  - The condition of music.

PMID- 11834780
TI  - Protein nanoarrays generated by dip-pen nanolithography.
AB  - Dip-pen nanolithography was used to construct arrays of proteins with 100- to 350
      nanometer features. These nanoarrays exhibit almost no detectable nonspecific
      binding of proteins to their passivated portions even in complex mixtures of
      proteins, and therefore provide the opportunity to study a variety of surface
      mediated biological recognition processes. For example, reactions involving the
      protein features and antigens in complex solutions can be screened easily by
      atomic force microscopy. As further proof-of-concept, these arrays were used to
      study cellular adhesion at the submicrometer scale.

PMID- 11834781
TI  - Placebo and opioid analgesia-- imaging a shared neuronal network.
AB  - It has been suggested that placebo analgesia involves both higher order cognitive
      networks and endogenous opioid systems. The rostral anterior cingulate cortex
      (rACC) and the brainstem are implicated in opioid analgesia, suggesting a similar
      role for these structures in placebo analgesia. Using positron emission
      tomography, we confirmed that both opioid and placebo analgesia are associated
      with increased activity in the rACC. We also observed a covariation between the
      activity in the rACC and the brainstem during both opioid and placebo analgesia,
      but not during the pain-only condition. These findings indicate a related neural
      mechanism in placebo and opioid analgesia.

PMID- 11834783
TI  - Is the Dongwanzi complex an Archean ophiolite?

PMID- 11834782
TI  - Systemic RNAi in C. elegans requires the putative transmembrane protein SID-1.
AB  - Double-stranded RNA-mediated gene interference (RNAi) in Caenorhabditis elegans
      systemically inhibits gene expression throughout the organism. To investigate how
      gene-specific silencing information is transmitted between cells, we constructed
      a strain that permits visualization of systemic RNAi. We used this strain to
      identify systemic RNA interference-deficient (sid) loci required to spread gene
      silencing information between tissues but not to initiate or maintain an RNAi
      response. One of these loci, sid-1, encodes a conserved protein with predicted
      transmembrane domains. SID-1 is expressed in cells sensitive to RNAi, is
      localized to the cell periphery, and is required cell-autonomously for systemic
      RNAi.

PMID- 11834784
TI  - Advancing science, serving society.

PMID- 11834785
TI  - High-energy physics. Troubled by glitches, Tevatron scrambles to retain its edge.

PMID- 11834786
TI  - Stem cells. German researchers get green light just.

PMID- 11834787
TI  - Cancer research. Leukemia protein spurs gene silencing.

PMID- 11834788
TI  - Genetics. DNA mutations linked to Soviet bomb tests.

PMID- 11834789
TI  - Nanotechnology. Nanowire fabricators earn their stripes.

PMID- 11834791
TI  - Mexico. Cuts add to turmoil over research spending.

PMID- 11834790
TI  - Neuroscience. Drugs and placebos look alike in the brain.

PMID- 11834792
TI  - Clinical research. Cancer study lawsuit dismissed in Oklahoma.

PMID- 11834793
TI  - France. CNRS under fire from government auditors.

PMID- 11834794
TI  - Genetics. Germany's elite tie knot with big pharma.

PMID- 11834795
TI  - Molecular computing. DNA-based computer takes aim at genes.

PMID- 11834796
TI  - 2003 budget. War effort shapes U.S. budget, with some program casualties.

PMID- 11834797
TI  - 2003 budget. NSF shines brightest in new good-government scorecard.

PMID- 11834798
TI  - 2003 budget. White House wants to shuffle, but will Congress dance?

PMID- 11834799
TI  - Circadian clock. How the brain's clock gets daily enlightenment.

PMID- 11834800
TI  - Primatology. Homeland defense in the wild.

PMID- 11834801
TI  - Vera Rubin profile. The bright face behind the dark sides of galaxies.

PMID- 11834802
TI  - Biotechnology. Some history should be repeated.

PMID- 11834803
TI  - Paleontology. Polar dinosaurs.

PMID- 11834804
TI  - Ecology. Incredible journeys.

PMID- 11834805
TI  - Biomedicine. Under pressure.

PMID- 11834806
TI  - Transcription. Mediator meets morpheus.

PMID- 11834807
TI  - Astronomy. Demotion looms for gamma-ray bursts.

PMID- 11834809
TI  - Mechanical circulatory support--a long and winding road.
AB  - The highly public reintroduction of the total artificial heart last year has
      prompted renewed interest in mechanical circulatory support systems for the
      treatment of end-stage heart disease.

PMID- 11834810
TI  - A space age vision advances in the clinic.

PMID- 11834811
TI  - Artificial blood.
AB  - Blood substitutes are under development for transfusion in place of donor blood
      during emergencies and lengthy surgeries. The first generation of blood
      substitutes is currently in clinical trials.

PMID- 11834812
TI  - Not blood simple.

PMID- 11834813
TI  - A bioartificial liver--state of the art.
AB  - End-stage liver disease is treated by liver transplantation, but donor organ
      shortages remain a serious problem. This has prompted the design of bioartificial
      liver devices to "bridge" patients until they either recover or receive a liver
      transplant. In these devices, patient plasma is circulated extracorporeally
      through a bioreactor that houses liver cells (hepatocytes) sandwiched between
      artificial plates or capillaries.

PMID- 11834814
TI  - Wanted: pig transplants that work.

PMID- 11834815
TI  - Tissue engineering--current challenges and expanding opportunities.
AB  - Tissue engineering can be used to restore, maintain, or enhance tissues and
      organs. The potential impact of this field, however, is far broader-in the
      future, engineered tissues could reduce the need for organ replacement, and could
      greatly accelerate the development of new drugs that may cure patients,
      eliminating the need for organ transplants altogether.

PMID- 11834816
TI  - Tending tender tendons.

PMID- 11834817
TI  - Third-generation biomedical materials.
AB  - Whereas second-generation biomaterials were designed to be either resorbable or
      bioactive, the next generation of biomaterials is combining these two properties,
      with the aim of developing materials that, once implanted, will help the body
      heal itself.

PMID- 11834818
TI  - New prospects for putting organs on ice.

PMID- 11834819
TI  - The bionic man: restoring mobility.
AB  - Bionics engineers are making increasingly bold and successful use of their tools
      to restore mobility to persons with missing or nonfunctional limbs. These tools
      include the latest materials, minielectronics and megacomputers, advanced robotic
      mechanisms, and algorithms. With crucial help from their pioneering users, they
      are learning how and where the residual sensorimotor system can be tapped in
      order to transmit its intents to replacement or reactivated body parts.

PMID- 11834820
TI  - Part man, part computer: researcher tests the limits.

PMID- 11834821
TI  - Will retinal implants restore vision?
AB  - A number of research groups are developing electrical implants that can be
      attached directly to the retina in an attempt to restore vision to patients
      suffering from retinal degeneration. However, despite promising results in animal
      experiments, there are still several major obstacles to overcome before retinal
      prostheses can be used clinically.

PMID- 11834822
TI  - Sending sound to the brain.
AB  - The cochlear implant, a microelectrode array that directly stimulates the
      auditory nerve, has greatly benefited many individuals with profound deafness.
      Deaf patients without an intact auditory nerve may be helped by the next
      generation of auditory prostheses: surface or penetrating auditory brainstem
      implants that bypass the auditory nerve and directly stimulate auditory
      processing centers in the brainstem.

PMID- 11834823
TI  - The confusing mix of hype and hope.

PMID- 11834824
TI  - Repairing the injured spinal cord.
AB  - Certain cell, molecular, and bioengineering strategies for repairing the injured
      spinal cord are showing encouraging results (either alone or in combination) in
      animal models, with limited recovery of mobility being reported in some cases.

PMID- 11834825
TI  - The quest to reverse time's toll.

PMID- 11834826
TI  - Cracking the secrets of aging.

PMID- 11834827
TI  - Nuclear weapons tests and human germline mutation rate.

PMID- 11834828
TI  - X-ray microdiffraction images of antiferromagnetic domain evolution in chromium.
AB  - Magnetic x-ray diffraction combined with x-ray focusing optics was used to image
      individual antiferromagnetic spin density wave domains in a chromium single
      crystal at the micron scale. The cross section for nonresonant magnetic x-ray
      scattering depends on the antiferromagnetic modulation vector and spin
      polarization direction and allows these quantities to be extracted independently.
      The technique was used to show that the broadening of the nominally first-order
      "spin-flip" transition at 123 kelvin, at which the spins rotate by 90 degrees C,
      originates at the walls between domains with orthogonal modulation vectors.
      During cooling, the transition begins at these walls and progresses inward. The
      modulation vector domains are themselves unchanged.

PMID- 11834829
TI  - Rutherford backscattering to study the near-surface region of volatile liquids
      and solids.
AB  - Here we describe the use of Rutherford backscattering spectrometry (RBS) to
      measure quantitative in situ elemental profiles with high depth resolution,
      online and nondestructively, in volatile substances (liquid and frozen acids,
      ice). Samples for analysis are held in a chamber with controlled temperature and
      partial pressures designed to match conditions for aerosols in Earth's
      atmosphere. This technique is demonstrated in studies of water solubility in
      sulfuric acid, hydrochloric acid (HCl) on ice surfaces, the formation of a HCl
      hexahydrate surface layer on evaporating HCl-doped ice, and the diffusion of
      water through this layer.

PMID- 11834830
TI  - Existence of an 16O-rich gaseous reservoir in the solar nebula.
AB  - Carbonaceous chondrite condensate olivine grains from two distinct petrographic
      settings, calcium-aluminum-rich inclusion (CAI) accretionary rims and amoeboid
      olivine aggregates (AOAs), are oxygen-16 (16O) enriched at the level previously
      observed inside CAIs. This requires that the gas in the nebular region where
      these grains condensed was 16O-rich. This contrasts with an 16O-poor gas present
      during the formation of chondrules, suggesting that CAIs and AOAs formed in a
      spatially restricted region of the solar nebula containing 16O-rich gas. The 16O
      rich gas composition may have resulted either from mass-independent isotopic
      chemistry or from evaporation of regions with enhanced dust/gas ratios, possibly
      in an X-wind environment near the young Sun.

PMID- 11834831
TI  - The mantle flow field beneath western North America.
AB  - Although motions at the surface of tectonic plates are well determined, the
      accompanying horizontal mantle flow is not. We have combined observations of
      surface deformation and upper mantle seismic anisotropy to estimate this flow
      field for western North America. We find that the mantle velocity is 5.5 +/- 1.5
      centimeters per year due east in a hot spot reference frame, nearly opposite to
      the direction of North American plate motion (west-southwest). The flow is only
      weakly coupled to the motion of the surface plate, producing a small drag force.
      This flow field is probably due to heterogeneity in mantle density associated
      with the former Farallon oceanic plate beneath North America.

PMID- 11834832
TI  - Structure, function, and activator-induced conformations of the CRSP coactivator.
AB  - The human cofactor complexes ARC (activator-recruited cofactor) and CRSP
      (cofactor required for Sp1 activation) mediate activator-dependent transcription
      in vitro. Although these complexes share several common subunits, their
      structural and functional relationships remain unknown. Here, we report that
      affinity-purified ARC consists of two distinct multisubunit complexes: a larger
      complex, denoted ARC-L, and a smaller coactivator, CRSP. Reconstituted in vitro
      transcription with biochemically separated ARC-L and CRSP reveals differential
      cofactor functions. The ARC-L complex is transcriptionally inactive, whereas the
      CRSP complex is highly active. Structural determination by electron microscopy
      (EM) and three-dimensional reconstruction indicate substantial differences in
      size and shape between ARC-L and CRSP. Moreover, EM analysis of independently
      derived CRSP complexes reveals distinct conformations induced by different
      activators. These results suggest that CRSP may potentiate transcription via
      specific activator-induced conformational changes.

PMID- 11834833
TI  - Linking breeding and wintering ranges of a migratory songbird using stable
      isotopes.
AB  - We used the natural abundance of stable isotopes (carbon and hydrogen) in the
      feathers of a neotropical migrant songbird to determine where birds from
      particular breeding areas spend the winter and the extent to which breeding
      populations mix in winter quarters. We show that most birds wintering on western
      Caribbean islands come from the northern portion of the species' North American
      breeding range, whereas those on more easterly islands are primarily from
      southern breeding areas. Although segregated by breeding latitude, birds within
      local wintering areas derive from a wide range of breeding longitudes, indicating
      considerable population mixing with respect to breeding longitude. These results
      are useful for assessing the effects of wintering habitat loss on breeding
      population abundances and for predicting whether the demographic consequences
      will be concentrated or diffuse.

PMID- 11834834
TI  - Melanopsin-containing retinal ganglion cells: architecture, projections, and
      intrinsic photosensitivity.
AB  - The primary circadian pacemaker, in the suprachiasmatic nucleus (SCN) of the
      mammalian brain, is photoentrained by light signals from the eyes through the
      retinohypothalamic tract. Retinal rod and cone cells are not required for
      photoentrainment. Recent evidence suggests that the entraining photoreceptors are
      retinal ganglion cells (RGCs) that project to the SCN. The visual pigment for
      this photoreceptor may be melanopsin, an opsin-like protein whose coding
      messenger RNA is found in a subset of mammalian RGCs. By cloning rat melanopsin
      and generating specific antibodies, we show that melanopsin is present in cell
      bodies, dendrites, and proximal axonal segments of a subset of rat RGCs. In mice
      heterozygous for tau-lacZ targeted to the melanopsin gene locus, beta
      galactosidase-positive RGC axons projected to the SCN and other brain nuclei
      involved in circadian photoentrainment or the pupillary light reflex. Rat RGCs
      that exhibited intrinsic photosensitivity invariably expressed melanopsin. Hence,
      melanopsin is most likely the visual pigment of phototransducing RGCs that set
      the circadian clock and initiate other non-image-forming visual functions.

PMID- 11834835
TI  - Phototransduction by retinal ganglion cells that set the circadian clock.
AB  - Light synchronizes mammalian circadian rhythms with environmental time by
      modulating retinal input to the circadian pacemaker-the suprachiasmatic nucleus
      (SCN) of the hypothalamus. Such photic entrainment requires neither rods nor
      cones, the only known retinal photoreceptors. Here, we show that retinal ganglion
      cells innervating the SCN are intrinsically photosensitive. Unlike other ganglion
      cells, they depolarized in response to light even when all synaptic input from
      rods and cones was blocked. The sensitivity, spectral tuning, and slow kinetics
      of this light response matched those of the photic entrainment mechanism,
      suggesting that these ganglion cells may be the primary photoreceptors for this
      system.

PMID- 11834836
TI  - Adult-onset primary open-angle glaucoma caused by mutations in optineurin.
AB  - Primary open-angle glaucoma (POAG) affects 33 million individuals worldwide and
      is a leading cause of blindness. In a study of 54 families with autosomal
      dominantly inherited adult-onset POAG, we identified the causative gene on
      chromosome 10p14 and designated it OPTN (for "optineurin"). Sequence alterations
      in OPTN were found in 16.7% of families with hereditary POAG, including
      individuals with normal intraocular pressure. The OPTN gene codes for a conserved
      66-kilodalton protein of unknown function that has been implicated in the tumor
      necrosis factor-alpha signaling pathway and that interacts with diverse proteins
      including Huntingtin, Ras-associated protein RAB8, and transcription factor IIIA.
      Optineurin is expressed in trabecular meshwork, nonpigmented ciliary epithelium,
      retina, and brain, and we speculate that it plays a neuroprotective role.

PMID- 11834837
TI  - Methyltransferase recruitment and DNA hypermethylation of target promoters by an
      oncogenic transcription factor.
AB  - DNA methylation of tumor suppressor genes is a frequent mechanism of
      transcriptional silencing in cancer. The molecular mechanisms underlying the
      specificity of methylation are unknown. We report here that the leukemia
      promoting PML-RAR fusion protein induces gene hypermethylation and silencing by
      recruiting DNA methyltransferases to target promoters and that hypermethylation
      contributes to its leukemogenic potential. Retinoic acid treatment induces
      promoter demethylation, gene reexpression, and reversion of the transformed
      phenotype. These results establish a mechanistic link between genetic and
      epigenetic changes during transformation and suggest that hypermethylation
      contributes to the early steps of carcinogenesis.

PMID- 11834838
TI  - Single-molecule speckle analysis of actin filament turnover in lamellipodia.
AB  - Lamellipodia are thin, veil-like extensions at the edge of cells that contain a
      dynamic array of actin filaments. We describe an approach for analyzing spatial
      regulation of actin polymerization and depolymerization in vivo in which we
      tracked single molecules of actin fused to the green fluorescent protein.
      Polymerization and the lifetime of actin filaments in lamellipodia were measured
      with high spatial precision. Basal polymerization and depolymerization occurred
      throughout lamellipodia with largely constant kinetics, and polymerization was
      promoted within one micron of the lamellipodium tip. Most of the actin filaments
      in the lamellipodium were generated by polymerization away from the tip.

PMID- 11834839
TI  - Generation of an LFA-1 antagonist by the transfer of the ICAM-1 immunoregulatory
      epitope to a small molecule.
AB  - The protein-protein interaction between leukocyte functional antigen-1 (LFA-1)
      and intercellular adhesion molecule-1 (ICAM-1) is critical to lymphocyte and
      immune system function. Here, we report on the transfer of the contiguous,
      nonlinear epitope of ICAM-1, responsible for its association with LFA-1, to a
      small-molecule framework. These LFA-1 antagonists bound LFA-1, blocked binding of
      ICAM-1, and inhibited a mixed lymphocyte reaction (MLR) with potency
      significantly greater than that of cyclosporine A. Furthermore, in comparison to
      an antibody to LFA-1, they exhibited significant anti-inflammatory effects in
      vivo. These results demonstrate the utility of small-molecule mimics of nonlinear
      protein epitopes and the protein epitopes themselves as leads in the
      identification of novel pharmaceutical agents.

PMID- 11834840
TI  - Evidence-based dermatology: a need to reset the agenda.
AB  - Evidence-based medicine (EBM) emphasises the role of clinical research in guiding
      clinical decisions. The aim is to integrate medical research into clinical
      practice in the most efficient way. In spite of EBM pointing to basic
      requirements for optimal patient care, the formalisation of an EBM approach is
      still at a developing stage in many areas of medicine, including dermatology. EBM
      should avoid becoming a specialised separate discipline with its own jargon and
      peculiar literature, i.e. secondary publications and systematic reviews. Ideally,
      the emphasis should be moved from so-called secondary to primary research, and an
      agreement on what constitutes research priorities should be reached on an
      international level with large-scale independent clinical studies being mounted
      by the dermatological community on unaddressed issues.

PMID- 11834841
TI  - Transposable elements and the lines of Blaschko: a new perspective.
AB  - BACKGROUND: Transposable elements or retrotransposons are particles of retroviral
      origin that are interspersed in large numbers in the genome of plants and
      animals. They may affect the activity of adjacent genes by methylation or
      demethylation, resulting in silencing or activation of gene expression. In
      animals such as mice or dogs, retrotransposons may give rise to phenotypic
      variation in the form of variegated coat patterns reminiscent of the lines of
      Blaschko as observed in human skin. OBJECTIVE AND METHODS: Because the human
      genome does likewise contain large amounts of retrotransposons, it is conceivable
      that these elements may cause similar skin lesions in human skin. The group of
      genodermatoses following the lines of Blaschko was therefore screened for
      phenotypes suggesting such an epigenetic origin. RESULTS: As possible examples,
      the inflammatory linear verrucous epidermal nevus as well as cases of pigmentary
      mosaicism arranged in hypermelanotic or hypomelanotic streaks following the lines
      of Blaschko may be taken into consideration. Such phenotypes usually occur
      sporadically but may affect, by way of exception, several members of a family.
      CONCLUSION: These linear skin disorders would possibly visualize the action of a
      transposable element that is partly expressed and partly silenced at an early
      developmental stage.

PMID- 11834842
TI  - Aquagenic syringeal acrokeratoderma (transient reactive papulotranslucent
      acrokeratoderma).
AB  - In 1996, English and McCollough described an unusual entity in 2 sisters
      characterized by a transient and recurrent keratoderma exclusively on the palms
      after water exposure. The condition developed 3-5 min after exposure to water and
      resolved within a short time after drying. This finding was associated with a
      tightening sensation. Yan et al. coined the term 'aquagenic palmoplantar
      keratoderma', and the designation 'aquagenic syringeal acrokeratoderma' was
      suggested by MacCormack et al. Until now, a total of 8 cases have been reported.
      We documented 2 new cases with acquired aquagenic syringeal acrokeratoderma. A 25
      year-old female had observed within the last 3 months a burning sensation on the
      palms after some minutes of water contact. Physical examination revealed a
      perfectly normal skin on the palms. Three minutes after water immersion of 20
      degrees C, a whitish discoloration appeared on the palms and a thickening of the
      palmar skin was visible. In addition, the eccrine pores were much more prominent.
      Few minutes after drying the skin, the situation returned to a normal state. The
      second patient, a 33-year-old female noticed a painful whitish discoloration of
      the skin on the palms after a short period of water immersion. Sometimes the
      white skin could be peeled off. In the last year, hyperhidrosis developed, and a
      more reddish aspect of the palms appeared. In our office after rinsing the hands
      with water at room temperature, a whitish discoloration in the center of the
      palms appeared which was associated with a painful sensation. After drying, the
      whitish lesions disappeared almost completely within 30 min. Aquagenic palmar
      keratoderma describes an acquired and transient condition which occurs after
      brief exposure to water and disappears after drying within minutes to an hour.
      Only rarely may a slight hyperkeratosis remain for a longer time. The possible
      pathophysiology and treatment options are discussed.

PMID- 11834843
TI  - Familial lymphocytic infiltration of the skin: histochemical and molecular
      analysis in three brothers.
AB  - BACKGROUND: Lymphocytic infiltration of the skin (Jessner and Kanof) is a T cell
      pseudolymphoma characterized by the occurrence of recurrent asymptomatic papules
      and plaques and by a coat-sleeve-like perivascular lymphoid infiltrate. Rarely,
      familial cases have been reported. OBJECTIVES: Our study was performed to address
      the question of a genetic predisposition in a case of familial lymphocytic
      infiltration by histochemical and molecular analysis. RESULTS: We report on 3
      brothers with typical clinical and histological features of Jessner's lymphocytic
      infiltration of the skin. Immunohistochemical analysis revealed a mixed
      lymphocytic infiltrate with a predominance of CD8+ T cells in all 3 patients.
      Molecular determination of T cell clonality by PCR-based GeneScan analysis of the
      T cell receptor (TCR)-gamma-chain showed oligoclonal, pseudomonoclonal or
      polyclonal TCR-gamma rearrangement patterns in lesional skin and in peripheral
      blood of all 3 brothers, while no common TCR idiotype was detected. CONCLUSION:
      Inherited deviations in TCR usage seem unlikely as a special cause of familial
      Jessner's lymphocytic infiltration of the skin; lack of clonality furthermore
      supports the notion that this variant of the disease is as true a pseudo-T-cell
      lymphoma as are the spontaneous cases.

PMID- 11834844
TI  - Postmenopausal aging of the sebaceous follicle: a comparison between women
      receiving hormone replacement therapy or not.
AB  - BACKGROUND: The endocrine control of sebaceous follicles is complex in women.
      During aging, a decline in sebum output is often experienced. However, some women
      report increased seborrhea after the menopause. OBJECTIVE: In this study, the
      follicular reservoir function was studied during the first decade following the
      menopause. METHODS: Four evaluations were made at 3-week intervals in two
      parallel age-matched groups of 50 postmenopausal women receiving hormone
      replacement therapy (HRT) or not. The Sebumeter served to measure the casual
      sebum level and the sebum excretion rate on the forehead. In addition, a
      Visioscan equipped with an ultraviolet-recording camera was used with and without
      lipid-sensitive tapes interposed between the camera and the skin surface.
      Follicular openings and sebum pore patterns were studied by image analysis.
      RESULTS: There was enormous diversity among individual values of sebum output at
      the skin surface. In untreated women, a significant decline in sebum excretion
      rate accompanied by an increase in both the sebum replacement time and the mean
      pore size were evidenced during the first decade after the menopause. The sebum
      excretion rate and casual level showed a wide range of interindividual
      differences early after the menopause. These physiological changes were less
      prominent in women receiving HRT. CONCLUSION: Postmenopausal aging affects the
      sebum production, but HRT does not significantly control the complex process of
      seborrhea. However, HRT mitigates the progressive enlargement of the openings of
      the sebum follicular reservoir.

PMID- 11834845
TI  - Sun exposure is an aggravating factor responsible for the recalcitrant facial
      erythema in adult patients with atopic dermatitis.
AB  - BACKGROUND: In Japan, a considerable number of adult patients with atopic
      dermatitis suffer from recalcitrant facial erythema that resists common treatment
      with topical corticosteroids and antihistamines. OBJECTIVE: Our purpose was to
      investigate the potential role of sun exposure in the aggravation of these facial
      lesions. METHODS: The history of photoaggravation was taken from 74 adult
      patients with atopic dermatitis who suffered from recalcitrant facial erythema.
      Repeated UVB and UVA phototests were performed in 36 patients. Surface markers of
      infiltrating cells in UVB-provoked lesions were characterized
      immunohistochemically. RESULTS: Forty-one of 74 patients experienced an
      exacerbation of the facial lesions after sun exposure. UVB testing revealed an
      abnormal, papular response in 14 of 36 patients. All of the 14 patients
      complained of clinical aggravation after sun exposure. No abnormal reactions were
      observed at UVA testing. In UVB-provoked lesions, CD4+ cells were predominant to
      CD8+ cells. CONCLUSION: Exposure to UVB radiation may be responsible for the
      recalcitrant facial erythema in at least some of the patients with atopic
      dermatitis.

PMID- 11834846
TI  - Scleroderma subsets are best detected by the simultaneous analysis of the
      autoantibody profile using commercial ELISA.
AB  - OBJECTIVE: Antinuclear antibodies are often present in patients with systemic
      sclerosis but do not provide useful prognostic information if studied
      individually. Although an autoantibody profile should be studied, this has never
      been done in a large series of patients. METHODS: Anticentromere, anti
      topoisomerase-I, anti-extractable-nuclear-antigen, antihistone and
      anticardiolipin antibodies were studied by means of enzyme immunosorbent assay in
      90 systemic sclerosis patients. RESULTS: We confirmed that anticentromere
      antibodies characterize limited forms of the disease with less frequent visceral
      involvement while anti-topoisomerase-I antibodies characterize diffuse forms with
      severe gastrointestinal, heart and lung involvement. Antihistone antibodies alone
      or associated with anticentromere antibodies characterize a disease subset with
      more frequent visceral involvement and a probably poor outcome. Patients with
      anticardiolipin antibodies, instead, did not display severer heart or vascular
      involvement. CONCLUSIONS: Systemic sclerosis patients are often found to have
      antinuclear antibodies. In addition to the well-known disease subsets identified
      by anti-topoisomerase-I and anticentromere antibodies, another one can be
      established, characterized by antihistone antibodies often associated with
      anticentromere antibodies. Patients displaying this profile have high prevalence
      of lung, kidney and heart involvement.

PMID- 11834847
TI  - Perception of baldness and hair density.
AB  - BACKGROUND: Androgenetic alopecia needs to be scored precisely. OBJECTIVE: A
      possible measure is the ratio between the hair density in the parietal area and
      that in the occipital area which, being not affected by baldness, supposedly has
      a 'normal' density. METHODS: On the vertex and just below the occipital
      protuberance of 109 men, two 1-cm(2) areas were identified. In both areas, hairs
      were clipped short and photographed by a videomicroscope. Hairs were then counted
      within a 30-mm(2)-wide central square section. RESULTS: In the occipital area,
      the average count was 127/cm(2), without differences among the Hamilton/Norwood
      classes. In the parietal area, the average density significantly diminished from
      138 to 47/cm(2). A main difference was found between classes 1-3 vertex and
      classes 4-6. CONCLUSIONS: The parietal/occipital ratio decreased significantly
      only when baldness was clinically manifest. The parietal/occipital ratio cannot
      be a better measure of baldness severity than the rough Hamilton/Norwood scale.
      The perception of early baldness does not depend on the diminished hair density,
      but also on the progressive thinning of the hair shafts.

PMID- 11834848
TI  - Dermatitis herpetiformis in Japan: an update.
AB  - BACKGROUND: Although dermatitis herpetiformis (DH) is a relatively common disease
      in Caucasian populations, it is rare in Asian populations including the Japanese.
      We encountered a Japanese case of DH which showed granular IgA and C3 deposits in
      the papillary dermis and which was associated with gluten-sensitive enteropathy
      but no HLA-B8/DR3/DQ2. OBJECTIVE: The purpose of this study is to describe the
      characteristics of Japanese DH cases, since most of them have been reported in
      Japanese language and dermatologists outside Japan are not familiar with the
      characteristics of Japanese DH. METHODS: We have reviewed all 34 Japanese DH
      cases reported previously. RESULTS: We found several features of Japanese DH
      compared with Caucasian DH, such as a high frequency of the fibrillar pattern,
      rarity of gluten-sensitive enteropathy and an absence of the HLA-B8/DR3/DQ2
      haplotype. CONCLUSION: There might be significant differences in pathophysiology
      between Caucasian and Japanese DH cases.

PMID- 11834849
TI  - Further evidence of the validity and reliability of the Skindex-29: an Italian
      study on 2,242 dermatological outpatients.
AB  - BACKGROUND: Quality of life is increasingly recognized as an important measure in
      dermatology. The Skindex-29 is a self-administered questionnaire recently
      developed to measure comprehensively the complex effects of skin diseases on
      patients' quality of life. OBJECTIVE: We aimed to provide further evidence of the
      reliability and validity of the Skindex-29 in a large sample of patients affected
      by a wide variety of skin diseases. METHODS: An Italian version of the Skindex-29
      was produced following accepted guidelines for the cross-cultural adaptation of
      questionnaires. All adult outpatients attending a dermatological hospital on
      predetermined days were given the Skindex-29 and the 12-item General Health
      Questionnaire (GHQ-12). RESULTS: A total of 2,242 complete questionnaires were
      analyzed. The internal consistency and test-retest reliability of each scale were
      high. The factor structure of the Skindex-29 was strikingly similar to the one
      originally observed in American patients. The pattern of correlation with the GHQ
      12 provided evidence of convergent validity of the Skindex-29. CONCLUSION: The
      instrument seems to measure three fundamental dimensions of skin health-related
      quality of life.

PMID- 11834850
TI  - Treatment of refractory atopic dermatitis using 'wet-wrap' dressings and diluted
      corticosteroids: results of standardized treatment in both children and adults.
AB  - BACKGROUND: 'Wet-wrap' dressings with diluted corticosteroids form an alternative
      treatment in patients with refractory atopic dermatitis (AD). OBJECTIVE: To
      evaluate a standardized treatment, using wet-wrap dressings with diluted
      corticosteroids, in patients with refractory AD. METHODS: Results of treatment,
      complications and possible side effects were retrospectively evaluated in 14
      children and 12 adults. RESULTS: Skin lesions improved dramatically during 1 week
      of inpatient treatment. A significant decrease in early-morning serum cortisol
      levels was measured. Levels below the normal range were only observed after 1
      week in 2 adults and on day 4 in 3 children. Suppression of the hypothalamus
      pituitary-adrenal-cortex axis in 1 adult and a new exacerbation of AD in 2
      children and 3 adults complicated long-term treatment at home. Additional
      complications included folliculitis, a Pseudomonas aeruginosa infection, a
      secondary bacterial infection and refractory skin lesions between bandages.
      CONCLUSION: Wet-wrap dressings and diluted corticosteroids form an effective
      treatment in patients with refractory AD.

PMID- 11834851
TI  - Topical steroids under wet-wrap dressings in atopic dermatitis--a vehicle
      controlled trial.
AB  - BACKGROUND: The wet-wrap dressing technique has proved to be beneficial in cases
      of exacerbated atopic dermatitis (AD) skin lesions. OBJECTIVE: The effect of wet
      wrap dressings was investigated in a controlled trial comparing a steroid
      (mometasone furoate 0.1%)-containing and a steroid-free (vehicle) preparation in
      an in-patient comparison study. METHODS: 20 children aged 2-17 years with
      exacerbated AD were treated twice daily with wet-wrap dressings over a 5-day
      period. RESULTS: AD in treated areas significantly improved in both study arms;
      however, the effect was significantly better in the mometasone-treated group (p <
      0.01). Transepidermal water loss improved in both arms without any significant
      differences. Staphylococcus aureus colonization decreased during the first 3 days
      of active treatment independently of the therapeutic modalities chosen. At day 5,
      colony counts further dropped on the steroid-treated lesions. CONCLUSION:
      Application of the wet-wrap dressing technique for exacerbated AD lesions is
      effective, combination with a topical steroid being superior to a steroid-free
      application without bearing the risk of a bacterial superinfection.

PMID- 11834852
TI  - Prevention and treatment of keloids with intralesional verapamil.
AB  - BACKGROUND: The current treatment of keloids is based on surgery, medical therapy
      and physical treatment. The optimal treatment remains undefined. OBJECTIVE: This
      clinical study determines the effectiveness of verapamil hydrochloride on the
      prevention and treatment of keloids. METHODS: Two groups of patients with keloids
      were divided according to lesion site and age. The first group was treated by
      perilesional surgical excision of keloids and topical silicone, combined with
      adjuvant treatment of intralesional 2.5 mg/ml verapamil hydrochloride injections
      administered at timed intervals. The second group served as control, receiving
      the same treatment except the verapamil hydrochloride. RESULTS: A periodical
      examination to check specific clinical parameters and an 18-month follow-up
      determined that keloids were cured in 54% of the cases in the first group,
      compared to 18% in the second group. Moreover, in the remaining 36% of patients
      in the first group in whom keloids recurred, there was an improvement in size and
      above all in consistence. CONCLUSION: These findings suggest that verapamil
      hydrochloride is an effective tool for the prevention and therapy of keloids.

PMID- 11834853
TI  - Low systemic exposure after repeated topical application of Pimecrolimus
      (Elidel), SD Z ASM 981) in patients with atopic dermatitis.
AB  - BACKGROUND: Pimecrolimus is a cell-selective inhibitor of inflammatory cytokine
      release developed specifically for the treatment of inflammatory skin diseases.
      AIM: The objective of this study was to evaluate blood concentrations and
      tolerability of pimecrolimus during topical treatment. METHODS: Twelve adult
      patients with extensive atopic dermatitis were enrolled in an open-label,
      noncontrolled, pharmacokinetic study. The patients were treated twice daily for 3
      weeks with pimecrolimus cream 1% on all lesions. Pimecrolimus blood
      concentrations were measured at regular time points, and the safety and
      tolerability were monitored throughout the study. RESULTS: In 78% of the 444
      blood samples evaluated, pimecrolimus concentrations remained below the limit of
      quantitation (0.5 ng/ml). The highest concentration measured was 1.4 ng/ml. There
      was no indication of drug accumulation. Pimecrolimus was well tolerated locally
      and systemically. CONCLUSION: The 3-week twice daily treatment with pimecrolimus
      cream 1% results in consistently low pimecrolimus blood concentrations with no
      accumulation. Pimecrolimus cream appears suitable for the long-term management of
      atopic dermatitis.

PMID- 11834854
TI  - Decreased oxidative state in non-lesional skin of atopic dermatitis.
AB  - BACKGROUND: The stratum corneum (SC), as the skin layer most exposed to various
      environmental factors, is particularly susceptible to oxidative stress. Due to
      the high lipid content of the SC, lipophilic antioxidants such as alpha
      tocopherol are expected to play a major role in scavenging reactive oxidant
      intermediates produced during oxidative stress. OBJECTIVES: Since the skin of
      atopic dermatitis patients has an impaired barrier function, we wondered if they
      were more susceptible to environmental oxidative stress than healthy subjects.
      METHODS: SC was collected by scraping the forearm of 14 healthy volunteers and 14
      patients with atopic dermatitis; then, alpha-tocopherol and lipid peroxide
      concentrations were assessed by high-performance liquid chromatography and
      ferrous oxidation, respectively. RESULTS: The SC from atopic patients showed a
      higher concentration of alpha-tocopherol (16.1 +/- 2.2 nmol/g) as compared to
      healthy controls (7.7 +/- 0.9 nmol/g; p < 0.01), as well as a slightly but
      significantly lower concentration of lipid peroxides (1,353 +/- 128 and 1,818 +/-
      154 nmol/g for atopic dermatitis patients and healthy controls, respectively; p <
      0.05). CONCLUSIONS: These results show that the SC of atopic dermatitis patients
      exhibits a significantly less pronounced oxidative state. This may be the
      consequence of an increase in cutaneous antioxidant defences due to chronic
      inflammation.

PMID- 11834855
TI  - Localized lymphomatoid papulosis.
AB  - A 50-year-old Japanese male visited our clinic in April 1999 with a 2-year
      history of self-healing, reddish papules on his right palm. On examination, there
      were grouped erythematous papules, 2-4 mm in size, which formed a relatively well
      circumscribed erythematous plaque. A biopsy specimen showed a wedge-shaped, dense
      dermal infiltrate consisting of variously sized mononuclear lymphoid cells mixed
      with few large CD30-positive cells and inflammatory cells, suggesting the
      diagnosis of regional lymphomatoid papulosis (LyP). Analysis of the T cell
      receptor gene revealed a polyclonal pattern on lesional skin. Only 5 cases of LyP
      presenting in a regional distribution have been reported previously. Although the
      etiology of localized LyP remains unknown, considering that 2 of 5 reported
      patients developed widespread lesions regional LyP may be the initial
      presentation of typical LyP.

PMID- 11834856
TI  - Combined vaccination by measles and hepatitis B vaccines: a new cause of Gianotti
      Crosti syndrome.
AB  - An 11-month-old boy presented with Gianotti-Crosti syndrome. He had received
      measles and a third dose of hepatitis B vaccines 2 weeks before the onset of the
      eruption. There were no clinical symptoms of any viral infection at the
      presentation. Serological tests for common viral infections were negative. The
      combination of measles and hepatitis B vaccines was likely the relevant factor in
      the etiology.

PMID- 11834857
TI  - The coexistence of photosensitive psoriasis with chronic actinic dermatitis.
AB  - A 57-year-old-male who had been a known case of psoriasis vulgaris for 30 years
      had a history of summer exacerbation of the disease. Subsequently in the course
      of the disease process, he developed lesions of chronic actinic dermatitis (CAD)
      on the face and dorsum of both hands. The association of CAD with photosensitive
      psoriasis is very rare. Only one case report is known till now. It may suggest
      that there is a relationship between the two diseases.

PMID- 11834858
TI  - Multinodular pilomatrixoma.
AB  - A hard deep nodule, 6 x 3 mm in size, was excised from the cheek of a 12-year-old
      girl. The histological sections showed a multinodular cyst-like proliferation,
      each nodule showing the typical structure and cytology of pilomatrixoma. A
      comparison is made between this case and the budding phenomenon that has been
      described in isthmus-catagen (tricholemmal) cyst.

PMID- 11834859
TI  - Multiple pilomatricoma in trisomy 9.

PMID- 11834860
TI  - Sweet's syndrome induced by oral contraceptive.

PMID- 11834861
TI  - Proceedings of the Fourth Conference on Endometriosis. April 28, 2001. Kanagawa,
      Japan.

PMID- 11834862
TI  - Endometriosis and infertility: is there a cause and effect relationship?
AB  - An association between endometriosis and infertility has long been noted.
      Endometriosis affects approximately 5% of the general population. In infertile
      women, the prevalence may be as high as 30%. Multiple studies, the majority of
      which are retrospective, indicate that the monthly fecundity of patients with
      endometriosis may be decreased by half compared to women without the disease. The
      precise cause-effect relationship between endometriosis and infertility remains
      controversial. In advanced cases of endometriosis, with distorted pelvic anatomy,
      the mechanism of infertility is more easily explained. Recent evidence suggests
      that treatment of early-stage endometriosis may increase pregnancy rates. Many
      etiologies of infertility in early-stage endometriosis have been proposed. These
      include endocrine dysfunctions such as luteal phase defect and luteinized
      unruptured follicle syndrome. In the last 15 years, alterations in the local
      pelvic immune environment have been the subject of multiple basic science
      investigations. Unfortunately, there is no satisfactory hypothesis that
      unequivocally explains the association of early stages of endometriosis with
      infertility.

PMID- 11834863
TI  - Complete removal of endometriosis improves fecundity.
AB  - Endometriosis is one of the causative factors of impaired fecundity. Whatever the
      mechanisms are of this impairment, surgical removal of endometriosis appears to
      increase postoperative fecundity. Our strategy in laparoscopic surgery for
      symptomatic endometriosis is to completely remove endometriosis. However, despite
      this strategy, laparoscopic surgery nonetheless creates two categories of
      patients; complete and incomplete surgery groups. We found by comparing the two
      groups that both were comparable in terms of fecundity during the early
      postoperative phase, whereas unlike the complete surgery group, fecundity in the
      incomplete surgery group stayed low during the late postoperative phase. Deep
      rectal endometriosis and deeply invading pelvic endometriosis are conditions
      wherein complete removal of endometriosis is difficult. We have developed
      laparoscopic surgeries for these conditions: laparoscopic anterior rectum slicing
      (LARS) and laparoscopic pelvic wall slicing (LPWS) operations, respectively. Both
      operations are effective in alleviating disease-related symptoms with minimal
      surgical invasiveness.

PMID- 11834864
TI  - Role of cytokines in endometriosis-associated infertility.
AB  - Endometriosis, which is common in women of reproductive age, may affect
      fertility. It is also clear that mechanical disruption of the pelvic anatomy may
      cause infertility. However, our understanding of the association between the
      early stage of endometriosis and infertility remains incomplete. Bloody
      peritoneal fluid (PF) is frequently observed in the cul-de-sac of endometriosis
      patients and contains various biologically active factors. We found that the
      concentrations of tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL
      6) in PF from patients with endometriosis were significantly higher than that of
      patients with endometriosis. There were significantly positive correlations
      between the levels of TNF-alpha and IL-6. We compared the levels of these
      cytokines with regard to the R-AFS stages and scores, but no differences were
      observed. In contrast, these cytokines correlate with the number and extent of
      red color peritoneal endometriosis. TNF-alpha increased the expression of IL-6
      messenger RNA and protein in endometriotic stromal cells derived from chocolate
      cyst in a dose-dependent manner. The addition of IL-6 inhibited the development
      of mouse preimplantation embryo and impaired sperm function. We concluded that
      increased levels of IL-6 in peritoneal fluid of patients with active red
      endometriosis might be related to endometriosis-associated fertility.

PMID- 11834865
TI  - Prediction of pregnancy in infertile women with endometriosis.
AB  - To estimate the probability of pregnancy in infertile women with endometriosis,
      two series of multivariate analyses were performed in Tohoku University Hospital.
      In the first series, from 1993 to 1997, 103 patients participated. The Cox
      proportional hazard regression model revealed a hazard ratio of 2.43 in patients
      with high ovarian adhesion scores. Bilateral ovarian adhesion was an important
      variable in anatomical factors, probably second only to bilateral tubal adhesion.
      In the next series, from 1998 to 1999, 23 patients were included, and the
      preoperative serum concentrations of cytokines, interleukin (IL)-6, IL-8, and
      tumor necrosis factor (TNF)-alpha were analyzed. Only TNF-alpha was selected with
      a forward stepwise analysis after forcing age and infertile duration. In the
      logistic regression model, the serum TNF-alpha level had a significant and
      negative impact on the likelihood of pregnancy.

PMID- 11834866
TI  - Role of laparoscopy in the treatment of endometriosis-associated infertility.
AB  - Endometriosis is assumed to be one of the causative factors of infertility,
      although the mechanism remains to be elucidated. Mechanical factors distorting
      the pelvic anatomy and/or changes in the biochemical and cellular environment in
      the peritoneal cavity are possible contributing factors impairing fertility.
      Laparoscopy is a widely used diagnostic and therapeutic means of treating
      endometriosis-associated infertility. However, pregnancy outcome after
      laparoscopy varies depending on preexisting tubal adhesions and endometriosis.
      Without tubal adhesions, the pregnancy rate is essentially the same irrespective
      of the presence or stages of endoemetriosis. Minimal/mild endometriosis benefited
      the most from laparoscopic manipulation when tubal adhesions were present. On the
      other hand, IVF-ET outcome of patients who previously underwent laparoscopy was
      not influenced by preexisiting tubal adhesions and endometriosis.

PMID- 11834867
TI  - Influence of pelvic endometriosis and ovarian endometrioma on fertility.
AB  - We investigated the influence of pelvic endometriosis and ovarian endometrioma on
      pregnancy outcome in women associated with infertility. A total of 237 women with
      endometriosis were reviewed, and their fertility rate was assessed by both r-AFS
      staging and TOP classification as previously proposed by our group. There was no
      significant difference in pregnancy rate among r-AFS stages. However, the
      pregnancy rate was mostly affected by the tubal condition according to the TOP
      classification as follows: no adhesive lesion (T0), 53% (69/129); unilateral
      lesion (T1), 46% (18/39); bilateral lesion with at least one tube patent, (T2),
      37% (10/27); bilateral tubal occlusion (T3), 0% (0/8) (p < 0.05, Mantel-Extension
      test). The absence (O0-O1) or co-existence (O2-O3) of ovarian endometrioma and
      different gradings of cul-de-sac obliteration (P2-P3) showed no significant
      differences in pregnancy rate. The resulting conception rate was also not
      affected by the size or location of ovarian endometrioma. In addition, the higher
      adhesion score of ovarian endometrioma involving the fallopian tube and as
      described in r-AFS classification had a significant detrimental effect on
      fertility. These observations suggest that our TOP classification describing
      individual tubal condition has a clinically predictive value in assessing the
      reproductive outcome of women with endometriosis.

PMID- 11834868
TI  - Endometriosis and oocyte quality.
AB  - Endometriosis is associated with marked subfertility and various causes for this
      subfertility have been previously studied. The poor quality of oocytes has been
      suggested as one possible cause. In this study, we evaluated the quality of
      oocytes by examining the status of granulosa cells surrounding the oocyte. For
      this purpose, we analysed the incidence of apoptosis, changes in cell cycle, and
      oxidative stress in the granulosa cells. Endometriosis patients had a higher
      apoptotic incidence, more alterations of the cell cycle, and a higher incidence
      of oxidative stress than patients with any of the other infertility causes (tube,
      male, and idiopathic factors). These changes might affect oocyte quality, and
      thus fertility in endometriosis patients.

PMID- 11834869
TI  - Pathogenesis of endometriosis.
AB  - Various theories have been promulgated to explain the pathogenesis of
      endometriosis. Interest in the genesis of the endometriotic lesion has been a
      focus since the earliest investigations. More recently, investigators have
      addressed aspects of the immune system and local peritoneal factors that may be
      involved with both the histogenesis of endometriosis as well as its sequelae.
      This review will consider evidence for different theories of histogenesis and
      will discuss our current understanding of the contribution of the immune system
      to the etiology of endometriosis. Data will be presented regarding recently
      described models of the early endometriotic lesion. The interaction of
      endometrial cells with the peritoneal mesothelium seems critical to our
      understanding the formation of the early endometriotic lesion. Evidence of rapid
      transmesothelial migration and invasion of the peritoneum will be considered. As
      well, candidate adhesion molecules that may facilitate the initial binding of
      endometrium to the peritoneum will be discussed.

PMID- 11834870
TI  - Effects of pravastatin on superoxide and fibronectin production of mesangial
      cells induced by low-density lipoprotein.
AB  - Pravastatin is a potent inhibitor of HMG-CoA reductase and is effective in
      lowering serum lipid levels. Recent studies have shown that pravastatin also
      reduces the oxidative modification of low-density lipoprotein (LDL). To determine
      whether pravastatin has a direct effect on glomerular mesangial cells, we have
      measured the effects of pravastatin on the production of superoxide and
      fibronectin of glomerular mesangial cells stimulated by LDL. Our results
      demonstrated that the superoxide production of mesangial cells increased after
      LDL stimulation (100 microg/ml for 4 h) and that the superoxide production was
      significantly suppressed by either superoxide dismutase (SOD; 500 U/ml for 36 h;
      p < 0.01) or pravastatin (80 microM for 36 h; p < 0.05). The production of
      fibronectin was also increased after LDL stimulation which was also significantly
      suppressed by either SOD (p < 0.01) or pravastatin (p < 0.01). SOD or pravastatin
      alone had no effect on the unstimulated cells. Our results indicate that
      pravastatin may have a direct effect as an antioxidant and suppresses the
      fibronectin synthesis of glomerular mesangial cells independent of its
      hypolipidemic effect.

PMID- 11834871
TI  - Glycosyl-phosphatidylinositol (GPI)-anchored renal dipeptidase is released by a
      phospholipase C in vivo.
AB  - The release mechanism of the glycosyl-phosphatidylinositol (GPI)-anchored renal
      dipeptidase (EC 3.4.13.19) in vivo has been investigated. Triton X-114 phase
      separation indicated that the dipeptidase is exclusively present as a hydrophilic
      form in urine from porcine, rat, rabbit and human. Western blot analysis of human
      and porcine purified dipeptidase and the urine concentrates with anti-(cross
      reacting determinant) serum demonstrated the presence of inositol 1,2-cyclic
      monophosphate indicating that the renal dipeptidase had been released from the
      membrane by the action of a phospholipase C. This is the first direct evidence
      for cleavage of a human GPI-anchored protein by a responsible phospholipase C in
      vivo.

PMID- 11834872
TI  - Tubular cell apoptosis and proliferation in the early phase of renal damage in
      uninephrectomized SHR.
AB  - In the present study, we measured tubular cell apoptosis and proliferation and
      Bcl-2 expression during the early phase (3 months) of the process of renal
      fibrosis in the experimental model of uninephrectomized spontaneously
      hypertensive rats (SHR). Tubulointerstitial fibrosis was evaluated by automated
      quantitative morphometry using selective staining of the extracellular matrix
      with sirius red. Apoptosis was quantified by both in situ dUTP biotin nick end
      labeling method (TUNEL) and by propidium iodide staining. Proliferation rate was
      measured by counting cells expressing the proliferating cell nuclear antigen. Bcl
      2 expression was assessed by immunohistochemistry. Tubulointerstitial fibrosis
      increased progressively during the 3 months of follow-up. Proliferation and
      apoptosis rates in tubular cells increased from the first to the second month
      after UNX. In the third month after UNX, the proliferating tubular cell number
      continued to increase, whereas the apoptotic cell number was maintained,
      coinciding with an increase in the expression of Bcl-2. Our observations
      demonstrate a different profile of tubular cell proliferation and apoptosis
      during the genesis of early tubulointerstitial damage in UNX-SHR.

PMID- 11834873
TI  - Nephron endowment and renal filtration surface area in young spontaneously
      hypertensive rats.
AB  - BACKGROUND/AIMS: A reduction in nephron endowment leading to reduced renal
      filtration surface area has been implicated in the development of hypertension.
      The aim of this study was to compare glomerular (and thereby nephron) number and
      renal filtration surface area in young Wistar-Kyoto rats (WKY) with young
      spontaneously hypertensive rats (SHR), prior to the development of hypertension
      in this model. METHODS: Using unbiased stereological methods the number and size
      of glomeruli, as well as total renal filtration surface area were determined in
      perfusion-fixed kidneys of 4-week-old WKY and SHR. RESULTS: At 4 weeks of age, in
      weight-matched animals, there was no significant difference in the number of
      glomeruli in the kidneys of SHR compared to WKY (28,620 +/- 1,643 and 25,670 +/-
      1,263 glomeruli/kidney, respectively). Similarly, there was no difference in mean
      glomerular volume (SHR: 4.70 +/- 0.31 x 10(-4) mm(3); WKY: 4.28 +/- 0.20 x 10(-4)
      mm(3)). Surprisingly, total renal filtration surface area was significantly
      greater in SHR than WKY (3,867 +/- 116 and 3,176 +/- 83 mm(2), respectively).
      CONCLUSION: The renal abnormality underlying the development of hypertension in
      the SHR is not due to inborn deficits in nephron endowment and/or filtration
      surface area.

PMID- 11834874
TI  - Renal effects of essential fatty acid deficiency in hydropenic and volume
      expanded rats.
AB  - The aim of this paper was to study the effects of essential fatty acid (EFA) on
      fractional sodium excretion (FE(Na(+))) and renal hemodynamics in rats during
      hydropenia (H) and acute volume expansion (VE), successively. Mean arterial
      pressure (MAP) and renal blood flow (RBF) were measured using a blood pressure
      transducer and a flow probe, respectively, both connected to a flowmeter.
      Glomerular filtration rate (GFR) was estimated by inulin clearance. The rats
      receiving coconut oil as only source of dietary lipids (the EFA-deficient group)
      presented lower levels of linoleic acid in cortex and medulla and lower body
      weight than the rats receiving soy oil in place of coconut oil (the control non
      EFA-deficient group). During H, the EFA-deficient rats exhibited a lower level of
      renal vascular resistance resulting in a higher level of RBF and a higher urinary
      flow (V') and FE(Na(+)), although GFR was lower than in the control group. During
      VE, the rats of the control group responded with increased MAP, RBF, V' and
      FE(Na(+)), which were not found in the EFA-deficient group, suggesting an
      impaired hemodynamic adjustment in EFA deficiency. In conclusion, both
      experimental conditions revealed that EFA deficiency affects the renal
      hemodynamics.

PMID- 11834875
TI  - Cardiovascular effects of beta-blockers with and without intrinsic
      sympathomimetic activity. A comparison between celiprolol and metoprolol.
AB  - BACKGROUND: Celiprolol, a newer beta-blocking agent, has been reported to have
      vasodilatory capacity which may be due to partial beta-2-receptor agonistic
      activity or to alpha-receptor antagonistic or central sympathoinhibitory effects.
      METHODS: To more critically assess the physiologic effects of celiprolol, we
      measured sympathetic nerve activity to muscle (MSNA), forearm blood flow (FBF),
      blood pressure (BP), central venous pressure, and heart rate (HR) in 10 normal
      volunteers at rest, during unloading of cardiopulmonary baroreceptors with lower
      body negative pressure (LBNP), and during a cold pressor test (CPT). Responses
      were compared with those seen with metoprolol and with placebo, i.e. each subject
      was studied three times. RESULTS: Celiprolol did not alter resting levels of
      hemodynamics, FBF, and MSNA nor did it alter responses to LBNP or the CPT. In
      contrast, metoprolol produced significant decreases of FBF and HR, and increases
      of forearm vascular resistance and BP, but had also no effect on responses to the
      applied stress tests. CONCLUSIONS: The lack of peripheral vasoconstriction seen
      after acute administration of celiprolol is most likely due to its partial beta-2
      receptor agonistic effect and does not seem to be due to a central or reflex
      action or to an alpha-blocking effect. Both beta-blockers do not impair
      fundamental neural mechanisms involved in circulatory homeostasis.

PMID- 11834876
TI  - Changes in renal and systemic hemodynamics after NO-synthase inhibition in males
      with family history of hypertension.
AB  - BACKGROUND: Nitric oxide (NO) plays an important role in the regulation of blood
      pressure and renal hemodynamics. METHODS: To further investigate the role of NO
      in human hypertension, we studied the effect of systemic injection of N(G)
      monomethyl-L-arginine (L-NMMA) on renal hemodynamics, urinary sodium excretion
      (FE(Na)), systemic hemodynamics and several vasoactive hormones in 5 healthy male
      subjects with (group H) and without (group N) family history of hypertension. An
      intravenous infusion of L-NMMA (3 mg/kg over 10 min) or placebo was given in a
      randomized, double-blinded manner. GFR and ERPF were measured by inulin- and PAH
      clearances. Norepinephrine infusion (0.1 microg/kg/min over 60 min) served as
      vasoconstrictive control infusion. RESULTS: L-NMMA induced a significant decrease
      in ERPF (-135 +/- 49 vs. 7 +/- 31 ml/min/1.73 m(2) with placebo, p < 0.05), a
      decrease in FE(Na) (-1.2 +/- 0.6% with L-NMMA vs. 0.0 +/- 0.1% with placebo), and
      a significant increase in diastolic blood pressure (+7 +/- 1 vs. -2 +/- 1 mm Hg
      with placebo) in group N, only. A sustained drop in plasma renin activity (-0.1
      +/- 0.1 vs. 0.3 +/- 0.1 ng/ml/h with placebo) could also be seen in this group,
      only. Subjects with family history of hypertension showed minor or even no
      response (changes in diastolic blood pressure: L-NMMA: 5 +/- 3 mm Hg, placebo: 0
      +/- 2 mm Hg; changes in ERPF: L-NMMA: -89 +/- 57 ml/min/1.73 m(2), placebo: -34
      +/- 28 ml/min/1.73 m(2); changes in plasma renin activity: L-NMMA: -0.0 +/- 0.3
      ng/ml/h, placebo: -0.1 +/- 0.2 ng/ml/h). The vasoconstrictive effect of
      norepinephrine infusion did not differ between both groups. CONCLUSION: Our data
      indicate that systemic NO synthetase inhibition by L-NMMA results in a blunted
      effect on systemic blood pressure and the renal hemodynamic system in subjects
      with family history of hypertension.

PMID- 11834877
TI  - Effect of dilazep dihydrochloride on serum cardiac troponin T levels in
      hemodialysis patients.
AB  - BACKGROUND/AIM: Cardiac troponin T is a highly sensitive marker for the detection
      of myocardial injury. We studied whether dilazep dihydrochloride affects cardiac
      troponin T levels in hemodialysis patients. METHODS: Our study included 60
      hemodialysis patients without symptoms of acute myocardial ischemia. We measured
      serum cardiac troponin T levels by the Elecsys troponin T assay and randomized 40
      hemodialysis patients with left ventricular hypertrophy (LVH) into two treatment
      groups: a dilazep dihydrochloride group (300 mg/day, n = 20) and a placebo group
      (n = 20). Treatment was continued for 12 months. RESULTS: There were no
      significant differences between pre- and postdialysis cardiac troponin T levels
      before treatment. LVH was noted in 40 patients out of 60 hemodialysis patients
      (67%). Cardiac troponin T levels were significantly higher in these patients
      (0.23 +/- 0.08 microg/l) than in hemodialysis patients without LVH (0.09 +/- 0.03
      microg/l). Cardiac troponin T levels were reduced from 0.24 +/- 0.08 to 0.12 +/-
      0.06 microg/l (p < 0.01) in patients treated with dilazep dihydrochloride. There
      were no change in cardiac troponin T levels in patients receiving placebo (from
      0.21 +/- 0.08 at baseline to 0.20 +/- 0.07 microg/l). CONCLUSION: Dilazep
      dihydrochloride may be effective in ameliorating myocardial damage in
      hemodialysis patients.

PMID- 11834878
TI  - Influence of the alpha-1-adrenergic receptor blocker doxazosin on exercise
      induced hyperkalemia in hemodialysis patients.
AB  - BACKGROUND/AIM: Hyperkalemic responses to both physical exercise and alpha
      adrenergic stimulation are enhanced in patients with terminal renal failure.
      Alpha-adrenergic blockade was found to protect against hyperkalemia during
      vigorous exercise in healthy men. The aim of the study was to examine the effects
      of the alpha-adrenergic blocker doxazosin on exercise-induced hyperkalemia in
      hemodialysis patients. METHODS: In a randomized, placebo-controlled, crossover
      design study, 15 anuric, chronic hemodialysis patients were included. Doxazosin
      or placebo was given in a random order for 4 days before exercise. At the end of
      each phase of the study, a 30-min treadmill exercise test with a constant
      workload of 2 metabolic equivalents was performed followed by a 30-min recovery
      period. RESULTS: The patients achieved 64 +/- 3 and 62 +/- 3% of maximal heart
      rate during the exercise test on doxazosin and placebo, respectively. The
      baseline plasma concentration of potassium was similar both on active treatment
      and on placebo (5.1 +/- 0.2 mmol/l on doxazosin and 4.9 +/- 0.1 mmol/l on
      placebo). The serum potassium concentration increased significantly and to a
      similar extent during the tests. The mean rates of potassium increment during
      exercise were 8.4 +/- 1.5 micromol/l/min on doxazosin and 6.9 +/- 1.3
      micromol/l/min on placebo. During the recovery period, the serum potassium
      concentration significantly decreased in both arms of the study. There were no
      significant changes in plasma sodium, calcium, and phosphate levels during the
      tests. Hydrogen ion concentration in blood, serum insulin and glucose, and plasma
      aldosterone and renin activity were similar before the exercise tests.
      CONCLUSION: Alpha-adrenergic blockade does not modulate the hyperkalemic response
      to moderate physical exercise in patients with terminal renal failure.

PMID- 11834879
TI  - Comparison of ondansetron with metoclopramide in the symptomatic relief of uremia
      induced nausea and vomiting.
AB  - BACKGROUND: Nausea and vomiting are well-known gastrointestinal complications in
      chronic renal failure and are frequent indications for the commencement of
      dialysis. Although the administration of antiemetic drugs (metoclopramide and,
      recently, ondansetron) is usually mentioned, there are scanty data on their
      effects. METHODS: A double-blind crossover study was done in 10 uremic patients.
      All the patients were uremic and suffered from nausea and vomiting. The drugs
      were randomly administered intravenously (either metoclopramide 10 mg or
      ondansetron 8 mg) 2 h after blood drawing for laboratory tests either on the 1st
      or on the 3rd study day at the same time. The outcomes were scored after 24 h of
      follow-up by (1) one of us (D.P.; 1-3 points: 1 = no effect; 2 = moderate effect 
      decreased frequency of vomiting, and 3 = good effect - no vomiting), and (2) by
      the patients (1-5 points). RESULTS: The results obtained showed that ondansetron
      was more effective in controlling nausea and vomiting than metoclopramide, either
      objectively (2.80 +/- 0.422 vs. 1.40 +/- 0.699, p < 0.005) or subjectively (4.10
      +/- 0.738 vs. 2.10 +/- 0.994, p < 0.005). CONCLUSIONS: We conclude that at the
      dosage level studied ondansetron is about twice as effective as metoclopramide in
      the symptomatic relief of uremia-induced nausea and vomiting.

PMID- 11834880
TI  - Development of posterior capsule opacification in the rabbit.
AB  - PURPOSE: The aim of the present study was to characterize the development of
      after-cataract in the rabbit by measuring its wet weight, protein, DNA and
      glycosaminoglycan (GAG) contents and using Scheimpflug and slitlamp analysis.
      Further, aqueous humor (AqH) leukocytes, protein and lens epithelial cell
      proliferation activity were determined. METHODS: AqH was collected and capsular
      bags including after-cataract were dissected free on days 0, 1, 7, 14, 28 and 56
      after cataract surgery. The wet weights were determined and the contents of DNA,
      protein and GAG in the capsular bags including after-cataract were analyzed. AqH
      was analyzed for leukocytes, protein and proliferative activity. In another set
      of experiments, rabbit eyes were analyzed by the Scheimpflug technique and
      slitlamp examination on days 0, 1, 7, 14, 28 and 56 after cataract surgery. The
      wet weight of the capsular bag with the after-cataract was also determined.
      RESULTS: An increase was found in the wet weight (480%) and the contents of
      protein (221%), DNA (945%) and GAG (336%) of the capsular bags including after
      cataract during the experimental period. In the AqH, all 3 variables measured,
      leukocytes, protein and proliferative activity, reached their highest levels on
      day 1 after surgery. In the second set of experiments, the wet weight of the
      capsular bag including after-cataract increased by 391% during the 56-day
      experimental period. Posterior capsule opacification (PCO), as measured by
      Scheimpflug analysis, increased from 0.8 to 81.7% and the scores of Elschnig's
      pearls as well as fibrosis, analyzed by slitlamp, increased from 0.0 to 2.8 and
      3.0, respectively. CONCLUSIONS: This study shows that the same components that
      are reported to be important in human PCO are also components of PCO in the
      rabbit. Thus, the rabbit model seems to accurately reflect human PCO development,
      and because PCO develops much faster in rabbits that would make the rabbit model
      suitable for studies to elucidate human PCO development.

PMID- 11834881
TI  - Pyruvate inhibits galactosemic changes in cultured cat lens epithelial cells.
AB  - An attempt was made to maintain cat lens epithelial cells (CLEC) in culture and
      study the morphology, growth and survival of these cells in vitro. The influence
      of incorporation of galactose (30 mM) into the culture medium on the morphology
      and biochemistry of CLEC in the primary culture was then investigated. To
      establish the effect of galactose on CLEC, various biochemical parameters
      associated with galactosemic cataract such as aldose reductase (AR), Na+K+ATPase,
      glutathione, polyol and soluble/insoluble proteins were estimated after 24 h of
      incubation. The effect of pyruvate (5 mM), a 'physiological antioxidant', on the
      changes induced by galactose in CLEC was studied. CLEC in culture showed regular
      hexagonal cells with prominent nuclei. The CLEC culture attained confluency in 11
      days during primary culture and semiconfluency in 14 days in two subsequent
      passages. Vacuolization and significantly raised AR activity, polyol levels and
      insoluble protein contents were observed; they had no effect on Na+K+ATPase and
      soluble protein after 24 h of incubation in the culture medium with galactose.
      Supplementation of pyruvate (5 mM) resulted in a lesser number of vacuoles
      together with a positive modulation of these parameters.

PMID- 11834882
TI  - Inhibition of lens epithelial cell migration by an acrylic intraocular lens in
      vitro.
AB  - We developed a new in vitro system to evaluate the effect of intraocular lenses
      (IOLs) on the migration of lens epithelial cells (LECs) and determined how
      acrylic and other IOLs influence LEC migration using this model. In an in vitro
      system, porcine LECs were cultured in a cell culture chamber insert, containing a
      collagen membrane, for 10 days with no IOL or with various types of IOLs.
      Migration of LECs beneath each IOL optic was observed with an inverted-phase
      microscope. The cell-free areas under the IOL optic, where the LECs had not
      migrated, were measured. Without IOL, LECs completely covered the collagen
      membrane within 5 days after plating (5.0 +/- 0.0 days). Complete coverage was
      slowed by a silicone IOL (6.7 +/- 1.2 days, p = 0.0305). LECs cultured with
      acrylic or with round- or sharp-edged polymethylmethacrylate (PMMA) IOLs did not
      completely cover the area. Ten days after initiating cultures, the cell-free
      areas under IOLs with sharp edges (acrylic, 41.1 +/- 8.0%; sharp-edged PMMA, 60.9
      +/- 39.0%) were significantly larger than under IOLs with round edges (silicone,
      0.0 +/- 0.0%; round-edged PMMA, 1.5 +/- 1.2%). A sharp edge may act as a barrier
      to LEC migration. Moreover, LEC migration under the acrylic IOL slowed after the
      LECs had crossed the barrier of the optic edge, perhaps due to acrylic adhesive
      properties. Only a few LECs reached the collagen membrane beneath the central 3
      mm of the acrylic IOL. This new in vitro model was useful in evaluating the
      effect of various IOLs on LEC migration. Acrylic IOLs inhibited LEC migration by
      not only a sharp edge but also other factors, such as adhesive properties.

PMID- 11834883
TI  - Gene expression of neurotrophins and their high-affinity Trk receptors in
      cultured human Muller cells.
AB  - PURPOSE: To investigate the gene expression of nerve growth factor (NGF), brain
      derived neurotrophic factor (BDNF), neurotrophin 3 (NT-3) and their high-affinity
      receptors (TrkA, TrkB and TrkC) in cultured human Muller cells. METHODS: The
      polymerase chain reaction was performed using specific primers for NGF, BDNF, NT
      3, TrkA, TrkB and TrkC with complementary DNAs as the template, which were
      generated from poly-A+ RNA of cultured human Muller cells. RESULTS: We detected
      the precursor mRNA transcripts for NGF, BDNF, NT-3, TrkB and TrkC, but not TrkA.
      CONCLUSION: Human Muller cells can direct mRNA expressions of a number of
      neurotrophins which may have a neurotrophic function in the retina. An autocrine
      mode of action is suggested, since Muller cells not only synthesize neurotrophic
      factors, but also express their specific receptors.

PMID- 11834884
TI  - Non-paralleled increase of hepatocyte growth factor and vascular endothelial
      growth factor in the eyes with angiogenic and nonangiogenic fibroproliferation.
AB  - Vascular endothelial growth factor (VEGF) has been known as principal angiogenic
      factor in vasculogenesis, tumor angiogenesis and ocular angiogenesis. Currently,
      hepatocyte growth factor (HGF) has been reported to play a major role in ocular
      angiogenesis. We studied distribution of both growth factors in angiogenic and
      non-angiogenic fibroproliferation to determine the correlation of VEGF and HGF in
      retinal angiogenesis. Concentrations of VEGF and HGF molecules in vitreous
      samples from 27 eyes with angiogenic proliferative diabetic retinopathy (PDR) and
      9 eyes with non-angiogenic proliferative vitreoretinopathy (PVR) were measured by
      enzyme-linked immunosorbent assay (ELISA). Vitreous samples with idiopathic
      macular role (IMH) served as a control. Concentrations of VEGF in the angiogenic
      PDR were 4.3 +/- 5.8 ng/ml (mean +/- SD), and were significantly higher than in
      non-angiogenic PVR (0.5 +/- 0.1 ng/ml). No significant differences were observed
      on VEGF concentrations between PVR to control. On the contrary, HGF
      concentrations were significantly higher in PVR (22.5 +/- 21.8 ng/ml) than in
      control (6.9 +/- 5.2 ng/ml), those of PDR (24.0 +/- 16.3 ng/ml) were also
      significantly higher than control. Among PDR samples, VEGF concentration was
      significantly higher than in the subgroup with higher angiogenic activity
      represented by iris neovascularization, although there were no significant
      differences on HGF concentration between the subgroups. Focal increases in HGF on
      fibroproliferation in the eye regardless of the involvement of angiogenesis were
      not in remarkable relation with angiogenic activity, unlike VEGF. These data
      suggested a more extensive role of HGF than VEGF strictly related to
      angiogenesis.

PMID- 11834885
TI  - Effect of topical betaxolol on the acute rise of aqueous flare induced by highly
      selective agonists for prostaglandin E2 receptor subtypes in pigmented rabbits.
AB  - PURPOSE: To evaluate the role of topical betaxolol on experimental ocular
      inflammation in rabbits. METHOD: Transcorneal diffusion of highly selective
      agonists for prostaglandin E2 receptor subtypes (EP), 25 microg/ml, with the use
      of a glass cylinder, was performed to produce aqueous flare elevation in
      pigmented rabbits. Betaxolol was topically administered before EP agonist
      application. Aqueous flare was measured with a laser flare cell meter. RESULTS:
      Performing topical instillation of 0.5% betaxolol 4 times inhibited 52 +/- 9% of
      EP2-agonist (ONO-AE1-259-01)-induced aqueous flare elevation. The inhibition of
      flare elevation was dependent on the number of betaxolol instillations. Betaxolol
      did not suppress the elevation induced by an EP4 agonist (ONO-AE1-392).
      CONCLUSION: Betaxolol inhibited EP2-agonist-induced aqueous flare elevation in
      pigmented rabbits.

PMID- 11834886
TI  - Voluntary self-administration of both morphine and cocaine by rats.
AB  - Voluntary self-administration of cocaine and/or morphine was studied in rats.
      Male rats were offered water bottles or bottles containing either cocaine or
      morphine, both cocaine and morphine (combination) or cocaine and morphine as a
      mixture. Alternating the three drug-containing bottles had no effect on drug
      choice. When offered alone, rats consumed about 12 +/- 8 mg/kg/day of cocaine or
      0.3 +/- 0.3 mg/kg/day of morphine. When both drugs were offered in combination,
      they consumed a higher amount of cocaine (22 +/- 7), but the same amount of
      morphine (0.4 +/- 0.3). Availability of cocaine/morphine mixture kept morphine
      consumption constant (0.3 +/- 0.1), but markedly decreased cocaine intake (0.3 +/
      0.2). Addition of saccharin to the drug solutions only slightly increased
      consumption of both drugs, whereas saccharin added as a competitor or distracter
      to the drug solution reduced cocaine but not morphine self-administration.
      Animals showed wide interindividual variations but surprisingly small
      intraindividual variations in self-administration of cocaine or morphine under
      all conditions. No correlation between cocaine and morphine intake was apparent
      in the combination situation. Forcing animals first with cocaine had no effect on
      subsequent intake of cocaine or morphine presented in combination. However,
      forcing animals first with morphine subsequently increased morphine and reduced
      cocaine intake. In conclusion, morphine intake was the same if offered alone, in
      combination or as a mixture, whereas cocaine intake increased during a
      combination but decreased in the mixture situation. Cocaine pre-exposure had no
      effect on subsequent voluntary morphine or cocaine choice, whereas morphine pre
      exposure increased subsequent voluntary morphine but decreased cocaine intake.
      These results suggest the possibility of two reward centers, one for each drug,
      the morphine center exerting a dominant influence over the cocaine center.

PMID- 11834887
TI  - Nefiracetam improves the impairment of local cerebral blood flow and glucose
      utilization after chronic focal cerebral ischemia in rats.
AB  - In this study we investigated the effects of nefiracetam (DM-9384) on local
      cerebral blood flow (LCBF) and local cerebral glucose utilization (LCMR(glc)) in
      the chronic phase after middle cerebral artery (MCA) occlusion in rats.
      Nefiracetam (10 mg/kg) was administered orally once a day for 2 weeks from day 15
      after MCA occlusion. On day 28 after MCA occlusion, LCBF and LCMR(glc) were
      measured by an autoradiographic image-processing method. In MCA-occluded rats,
      LCBF and LCMR(glc) in the ischemic side of seven regions including the frontal
      cortex were significant decreased compared with those of the nonischemic side.
      Nefiracetam significantly improved the impairment of LCBF in the frontal cortex,
      parietal cortex, caudate putamen, ventral thalamus, amygdaloid nucleus and
      hippocampus. It also improved the decrease of LCMR(glc) in the frontal cortex,
      ventral thalamus and hippocampus. These results suggested that nefiracetam has
      ameliorating effects on chronic disorders of LCBF and LCMR(glc) induced by MCA
      occlusion.

PMID- 11834888
TI  - Comparison of furosemide and vinblastine secretion from cell lines overexpressing
      multidrug resistance protein (P-glycoprotein) and multidrug resistance-associated
      proteins (MRP1 and MRP2).
AB  - Recent studies in our laboratory have shown that the loop diuretic, furosemide,
      is actively secreted by Caco-2 cells and rat jejunal tissue. This active
      secretion could be the result of efflux transporters such as P-gp, MRP1 or MRP2
      (cMOAT). To determine if any of these transporters is responsible for the
      secretion of furosemide, we compared directional permeability in the wild-type
      cell lines, MDCK strains I and II, and LLC-PK1, vs. cell lines that overexpress a
      single transporter, in both the presence and absence of various inhibitors, for
      furosemide as compared to vinblastine. Sulfinpyrazone significantly inhibited the
      transport of vinblastine in MRP2 expressing cells, but not the wild-type
      controls. Vinblastine could not be confirmed as a substrate of MRP1. We were also
      unable to demonstrate that any particular transporter affected furosemide in
      excess of the background effects of endogenous transporters in the parental cell
      lines. Furosemide secretion from these kidney-derived cell lines is probably not
      the primary result of any of the well characterized efflux transporters (P-gp,
      MRP1 or MRP2), although they may still play a role in the observed Caco-2
      secretion. This equivocal result acknowledges the difficulty in trying to
      determine the effect of a single protein in a complicated expression system.

PMID- 11834889
TI  - Nitric oxide stimulates adrenomedullin secretion and gene expression in
      endothelial cells.
AB  - Adrenomedullin, a peptide with vasorelaxant activity, stimulates nitric oxide
      (NO) synthesis. We tested whether or not NO regulates the function of the
      adrenomedullin system. Human umbilical vein endothelial cells (HUVEC) were
      incubated with the NO donors sodium nitroprusside (SNP), morpholinosydnonimine
      (SIN-1) and the phospodiesterase V inhibitor zaprinast. In HUVEC, adrenomedullin
      concentration in the supernatant was measured by radioimmunoassay and mRNA
      expression was studied by Northern blot and competitive quantitative PCR. SNP,
      SIN-1, and zaprinast (100 micromol/l each) significantly increased adrenomedullin
      concentration in the supernatant of HUVEC twofold. The same concentrations
      increased adrenomedullin mRNA expression four- to tenfold. Similar results were
      obtained by both quantitative PCR and Northern blot. Thus, NO donor exposure in
      vitro increases both adrenomedullin secretion and mRNA expression in a dose
      dependent manner.

PMID- 11834890
TI  - Relationship between prostatic alpha(1)-adrenoceptor binding and reduction in
      intraurethral pressure following continuous infusion of KMD-3213 in rats.
AB  - The relationship between alpha(1)-adrenoceptor binding in rat tissues and
      pharmacodynamic effects of continuous infusion of KMD-3213 was examined. In vivo
      specific binding of [(3)H]KMD-3213 after continuous intravenous infusion of the
      ligand (100 pmol/kg/min for 10 min, followed by 30 pmol/kg/min for 60 or 90 min)
      differed largely among the tissues examined. Specific binding of [(3)H]KMD-3213
      in aorta, heart, lung, and kidney was not different in terms of infusion time in
      the case of continuous infusion for 10, 70 and 100 min, whereas the binding in
      prostate, vas deferens, and submaxillary gland by 70- and/or 100-min infusion was
      significantly greater than that by the 10-min infusion. A similar extent of
      specific binding in the prostate was observed by the infusion (100 min) of a
      three-fold higher dose of [(3)H]KMD- 3213. Continuous intravenous infusion of KMD
      3213 (100 pmol/kg/min for 10 min, followed by 30 pmol/kg/min) for 70 or 100 min
      significantly reduced the phenylephrine-induced increase in the mean blood
      pressure and that in the intraurethral pressure of anesthetized rats. Extent and
      time course of the KMD-3213 effect reduction in the phenylephrine-induced
      increase in intraurethral pressure were closely associated with those in
      prostatic [(3)H]KMD-3213 binding after continuous infusion of the corresponding
      dosage of the radioligand. The reduction in the phenylephrine-induced increase by
      the infusion of a three-fold higher dose of KMD-3213 was significantly greater in
      the case of the intraurethral pressure than in that of the mean blood pressure,
      thereby suggesting a greater selectivity for the alpha(1)-adrenoceptor in the
      lower urinary tract than for that in the vascular tissue. In conclusion, the
      present study has shown that specific binding of [(3)H]KMD-3213 in the rat
      prostate after the continuous intravenous infusion of the radioligand may be
      closely associated with the pharmacological effect of this drug on the lower
      urinary tract.

PMID- 11834891
TI  - Alteration of M(3) subtype muscarinic receptors in the diabetic rat urinary
      bladder.
AB  - The M(3) receptor (M(3)-mAChR) is the major muscarinic subtype in the animal
      bladder responsible for detrusor contraction. The alterations in its protein
      quantity and biosynthesis during diabetic cystopathy were investigated. 3-month
      old male Wistar rats were divided into two groups: (1) 2-week diabetic rats and
      (2) normoglycemic control rats. Diabetes was induced by a single intravenous
      injection of 60 mg/kg streptozotocin. The amount of M(3) receptor protein in the
      rat bladder body tissue was measured by Western immunoblotting using monoclonal
      antibodies. For determination of M(3) muscarinic receptor mRNA in the bladder
      tissue, the method of Northern blotting was employed. The results of the Western
      immunoblotting showed that the amount of M(3)-mAChR protein in the diabetic
      bladder was significantly increased by about 70.2 +/- 8.5% when compared to the
      control bladder (p < 0.05, n = 8). Northern blotting demonstrated a 54.7 +/- 6.0%
      increase of M(3)-mAChR mRNA in the diabetic bladder (p < 0.05, n = 8). The
      findings of the present study demonstrated an upregulation of M(3)-mAChR
      biosynthesis in the diabetic urinary bladder. This phenomenon offers an
      explanation of the increased contractility after muscarinic stimulation of the
      detrusor muscle of diabetic animals.

PMID- 11834892
TI  - Binding of the active metabolite of chloral hydrate, 2,2,2-trichloroethanol, to
      serum albumin demonstrated using tryptophan fluorescence quenching.
AB  - Chloral hydrate, a sedative/hypnotic agent widely used in the pediatric
      population, is converted to the active metabolite 2,2,2-trichloroethanol (TCE) in
      the liver. Tryptophan fluorescence quenching has been used previously to show
      that halothane and chloroform bind saturably to serum albumin, and a similar
      approach is used here to demonstrate that TCE also binds to albumin. TCE quenches
      the steady-state tryptophan fluorescence of bovine serum albumin (BSA) in a
      concentration-dependent, saturable manner with a K(D) = 3.3 +/- 0.3 mmol/l.
      Unlike halothane and chloroform, however, TCE also elicits a concentration
      dependent blue-shift in the fluorescence emission spectrum of BSA and human serum
      albumin. This indicates that TCE induces a conformational change in the protein,
      causing the tryptophan to experience a change in its chemical environment, thus
      shifting the peak of the emission spectrum. Circular dichroism spectroscopy
      revealed a decrease in the alpha-helical content of BSA from 65.8 +/- 0.4 to 62.9
      +/- 0.6% when TCE was present at a concentration of 30 mmol/l, providing further
      evidence for a conformational change. There is evidence that TCE potentiates the
      action of ligand-gated ion channels such as the GABA(A) and 5-HT(3) receptors,
      and the present results suggest that anesthetic alcohols may act by binding to
      these proteins and inducing structural changes that may in turn alter protein
      function.

PMID- 11834893
TI  - Opposite biological effects of arsenic trioxide and arsacetin involve a different
      regulation of signaling in human gastric cancer MGC-803 cells.
AB  - Opposite biological effects of arsenic trioxide (As(2)O(3)) and arsacetin on the
      growth of human gastric cancer MGC-803 cells have been observed. Results show
      that As(2)O(3) inhibited the growth of MGC-803 cells by triggering apoptosis,
      whereas arsacetin promoted the cell proliferation and seemed to stimulate the
      secretion of some growth factors at the same micromolar concentrations. Further
      studies showed that As(2)O(3) could regulate protein tyrosine kinase activity,
      protein tyrosine phosphorylation, and Bcl-2 protein and upregulate p53 protein.
      The ability of arsacetin to promote cell proliferation is linked with causing the
      opposite effects on these factors. These results indicate that the opposite
      biological effects of As(2)O(3) and arsacetin involve different regulations of
      molecular mechanisms in MGC-803 cells and that arsacetin may be a potential tumor
      promoter.

PMID- 11834894
TI  - Nutrition and risk of prostate cancer.

PMID- 11834895
TI  - Hypospadias: incidence and effects on psychosexual development as evaluated with
      the Minnesota Multiphasic Personality Inventory test in a sample of 11,649 young
      Italian men.
AB  - PURPOSE: We evaluated the incidence of hypospadias and its effects on
      psychosexual development in a sample of 11,649 young Italian males. Over the last
      30 years only about 30 major publications have addressed these issues and the
      results of many studies have been contrasting. Some defects in methodology, such
      as low response rates, heterogeneity of age ranges and the choice of controls,
      have been the main limitations. Our study was designed to take these problems
      into account. MATERIALS AND METHODS: Forty-two hypospadic subjects and a random
      sample of 500 nonaffected males selected from the large sample of 11,649 young
      men (>90% of the 18-year-old males living in the Italian region of Tuscany) were
      screened by the Minnesota Multiphasic Personality Inventory (MMPI) test,
      psychological interview and clinical evaluation. RESULTS: The incidence of
      hypospadias in this representative group of Italian men is 3.6/1,000. No
      difference was noted in the percentage with altered MMPI compared with the
      control group. The age at surgical corrections and the number of operations are
      not related to an abnormal global psychological adjustment. Severity of disease
      influences a more negative genital appraisal and the number of operations is
      correlated only with more difficulty in initiating contact with the opposite sex.
      CONCLUSIONS: Surgery for hypospadias has to be strongly pursued in as many cases
      as possible. In addition, we strongly recommend following up all hypospadics,
      independently of the severity of their genital malformations, through adolescence
      to early adulthood, to ensure early detection of subjects with impaired
      psychological profiles.

PMID- 11834896
TI  - Percutaneous testicular sperm aspiration and intracytoplasmic sperm injection in
      obstructive and non-obstructive azoospermia: an easy alternative to TESE and
      MESA.
AB  - OBJECTIVE: To evaluate the recovery rate of sperm from the testis using
      percutaneous testicular aspiration with a 22-gauge hypodermic needle followed by
      evaluation of the fertilization rate and pregnancy rate after intracytoplasmic
      sperm injection. MATERIALS AND METHODS: This is a prospective observational study
      performed in a private in vitro fertilization setting in Kuwait. Fifteen patients
      with obstructive and non-obstructive azoospermia were included in the study.
      Thirteen of them had previous microepididymal sperm aspiration, percutaneous
      epididymal sperm aspiration or testicular sperm extraction. The sperm were
      retrieved using percutaneous testicular aspiration under local analgesia. This
      was followed by intracytoplasmic sperm injection. A total of 146 eggs were
      collected and 112 were injected. RESULTS: Normal fertilization occurred in 91
      oocytes (87.5%) and the total number of embryos cleaved was 83 (91%). Embryo
      transfer was performed in 13 with pregnancy rate of 33.3 per treatment cycle and
      38.5 per embryo transfer. Failure to retrieve sperm was encountered in 2 cases
      both in the hypospermatogenesis group. CONCLUSIONS: Percutaneous testicular sperm
      aspiration using hypodermic needles under local analgesic is an easy and cheap
      method with high patient acceptability, minimal complications and no need of
      special training. In this small group, it seems to have an acceptable success
      rate in terms of sperm retrieval and pregnancy in the obstructive type as well as
      hypospermatogenesis, but to lesser extent.

PMID- 11834897
TI  - Peyronie's disease: corporoplasty using saphenous vein patch graft.
AB  - OBJECTIVE: To establish who the best candidates for corporoplasty are. The
      standard guidelines include patients with partial erections, and/or recurvature
      preventing normal and satisfying intercourse. In our unit we prefer to implant
      prostheses even in patients with slight erectile dysfunction, therefore patients
      with full erections routinely undergo corporoplasty. MATERIALS AND METHODS: We
      report our experience with corporoplasty using a vein patch graft after plaque
      incision or excision in 12 patients affected by Peyronie's disease. RESULTS: The
      operation is easy to perform. Recovery of normal spontaneous erectile activity
      was observed in 10/12 (83%) patients at a mean of 1 month postoperatively. The
      results of checkups with Rigiscan and EchocolorDoppler have confirmed the
      stability of the graft and recovery of potency. DISCUSSION: Autologous material
      is easy to harvest and it is elastic enough to support traction during erection.
      The patch can be modelled to fashion patches in any shape required. The risk of
      scar shrinkage, with the consequent onset of recurvature, is lower than with
      other materials such as Gore-tex or Derma. Corporoplasty ensured rapid
      rehabilitation of sexual functions in all patients. We do not usually perform the
      Nesbit procedure as shortening of the penis (which is characteristic of
      Peyronie's disease) would, in most patients, be accentuated by albuginea
      plication.

PMID- 11834898
TI  - Observational multicentric trial performed with doxazosin: evaluation of sexual
      effects on patients with diagnosed benign prostatic hyperplasia.
AB  - INTRODUCTION: The aim of our study is to verify the effects of doxazosin on
      sexual function in patients with benign prostatic hyperplasia (BPH). MATERIALS
      AND METHODS: We enrolled 102 patients with BPH, selected by nine Italian Urology
      Departments. Patients were evaluated with the International Prostatic Symptom
      Score (I-PSS) and divided into two groups: those with intact sexual activity and
      those with erectile dysfunction. According to the International Index of Erectile
      Function (IIEF), the second cohort was divided into three subgroups on the basis
      of the degree of erectile dysfunction degree (severe, moderate or mild). All
      patients underwent 3 months of therapy with doxazosin. The effects of doxazosin
      on sexual activity and on voiding symptoms were monitored at 1, 2 and 3 months
      with IIEF and I-PSS scales. RESULTS: Eighty-six of the 102 initial patients (84%)
      were monitored until follow-up was completed. The follow-up at 1 month showed a
      significant decrease in the I-PSS (p < 0.0001) from 20.2 +/- 2.01 (base visit) to
      13.1 +/- 2.21. The mean IIEF was 19.24 +/- 6.59 at baseline and 1 month later the
      score reached 21.44 +/- 5.40, thus showing a statistically significant increase
      (p = 0.0177). This is more evident in the group presenting with severe to
      moderate erectile dysfunction. I-PSS and IIEF do not significantly change at the
      2- and 3-month follow-ups. CONCLUSIONS: The use of doxazosin improved sexual
      function in patients with BPH.

PMID- 11834899
TI  - Analysis of the pathophysiology of lower urinary tract symptoms in patients after
      prostatectomy.
AB  - OBJECTIVES: To analyze the pathophysiology of persistent lower urinary tract
      symptoms (LUTS) in patients after transurethral prostatectomy (TURP). METHODS: A
      total of 185 patients who had persistent LUTS after TURP were enrolled into this
      study. All of these patients underwent multichannel videourodynamic studies and
      were classified into 6 groups according to the urodynamic results. Preoperative
      prostate volume, resected adenoma weight, and preoperative Q(max) were determined
      in each of the groups and the symptomatology and urodynamic findings were
      compared. RESULTS: A normal videourodynamic tracing was found in 17 patients
      (9.1%), pure detrusor instability in 18 (9.6%), low detrusor contractility in 35
      (18.7%), detrusor instability and inadequate detrusor contractility (DHIC) in 27
      (14.4%), poor relaxation of the urethral sphincter in 36 (19.3%), and bladder
      outlet obstruction (BOO) in 52 (27.8%). Incontinence was noted in 74 patients
      (40%), and 18 of them had BOO (24.3%). In urodynamic findings, Q(max) and
      residual urine showed no significant difference among patients with low
      contractility, poor relaxation of sphincter, DHIC and BOO. Concerning the
      preoperative prostatic volume, patients with low contractility, poor relaxation
      of urethral sphincter, and DHIC had a nonsignificantly smaller prostate volume
      and resected prostate weight than other groups. Preoperative Q(max) showed no
      significant difference among all groups. CONCLUSIONS: Symptoms alone are
      unreliable in predicting urodynamic findings with respect to obstruction and
      detrusor instability after TURP. Over half of the patients with persistent LUTS
      had a small prostate volume and small resected adenoma weight, indicating that
      some of these patients may not have had BOO. Videourodynamic study is helpful in
      making an accurate diagnosis for refractory LUTS after TURP.

PMID- 11834900
TI  - Early catheter removal following transurethral prostatectomy: overnight
      catheterization.
AB  - OBJECTIVE: Our aim was to determine the safety and feasibility of catheter
      removal on the first morning after transurethral prostatectomy. METHODS: Fifty
      four patients who underwent transurethral prostatectomy were included in a
      prospective study. The decision to remove the catheters on the first morning
      after surgery was based on the color of the catheter effluent, absence of clots,
      normal vital signs and adequate urine output. Patients who voided successfully
      were discharged on the same day as catheter removal. RESULTS: Catheters were
      removed in 43 (79.6%) patients on postoperative day 1. Of these patients 40 (93%)
      voided successfully, however 3 of them required recatheterization due to bleeding
      or urinary retention. The criteria for catheter removal were not met in 11
      patients and their catheters were removed on postoperative day 2 in 2 and on
      postoperative day 3 in 9. The mean length of hospital stay after surgery was 1.74
      days for the entire group and 1.41 days for those in whom the catheter was
      removed on postoperative day 1. CONCLUSION: Overnight catheterization after
      transurethral prostatectomy seems to be a feasible approach without leading to
      significant morbidity in selected patients.

PMID- 11834901
TI  - Improved continence after radical retropubic prostatectomy using two pubo
      urethral suspension stitches.
AB  - OBJECTIVES: To determine if placement of urethral suspension stitches during
      radical retropubic prostatectomy improves postoperative urinary continence.
      METHODS: Between January 1997 and January 1998 we performed radical retropubic
      prostatectomy on 50 men. The first 25 consecutive men had their surgery without
      urethral suspension stitches while the next 25 received placement of two
      anastomotic urethral suspension stitches anchored to the lower portion of the
      pubic bone. Patients were interviewed six months postoperatively and each
      underwent valsalva leak-point pressure measurement. Patients were categorized as
      either completely continent (requiring no pads and having no measurable valsalva
      leak point), socially continent (zero or one pad per day), or incontinent (two or
      more pads per day). RESULTS: In the urethral suspension group, 8/25 (32%)
      patients were completely continent and did not have a measurable valsalva leak
      point pressure while 3/25 (12%) without urethral suspension were completely
      continent. Of the remaining patients in the urethral suspension group, 13/17
      (76%) patients were socially continent while 4/17 (24%) were incontinent. The
      mean valsalva leak-point pressure in the 17 patients with suspension stitches was
      89.6 +/- 21.6 cm H2O. In the patients without urethral suspension, there were 22
      patients who had some degree of incontinence. Among non-stitch patients, 13/22
      (59%) were socially continent while 9/22 (41%) were incontinent. The average
      valsalva leak-point pressure in these patients was 74.0 +/- 16.7 cm H2O, which
      was significantly lower than those with the suspension (p = 0.015). CONCLUSIONS:
      Placement of anastomotic urethral suspension stitches during radical retropubic
      prostatectomy may increase the likelihood of complete postoperative urinary
      continence. The urethral suspension stitches also increase valsalva leak-point
      pressure, which may improve the percentage of patients with socially acceptable
      incontinence.

PMID- 11834903
TI  - Influence of cations and total protein of urine on the solubility and probability
      of urate stone formation in kidneys.
AB  - The solubility of uric acid kidney stones has been studied in water solutions
      containing ammonium ions, alkaline ions and alkaline earth metals. It was shown
      that the solubility of uric acid stones depends on the concentration of these
      cations. The shape of the dependence curve of uric acid stone solubility in
      solutions containing cations of ammonium, sodium, potassium, calcium and
      magnesium has an extreme character. It was shown that a maximal balanced
      solubility of stones occurs in solutions in which the concentrations and ratios
      of the cations concentrations are equal to their 'normal' value in the urine of
      healthy persons. The solubility dependence of stones on ammonium ions does not
      show any extreme and is well approximated with the exponent. Correlation analysis
      of the above-mentioned cations and also of total protein in urine was carried out
      in healthy people and patients with uric acid stones. The relationship was
      determined between the concentrations of cations and total protein in urine, and
      the formation of uric acid stones in human kidneys.

PMID- 11834902
TI  - Biopsies of the transitional zone of the prostate. Should it be done on a routine
      basis, when and why?
AB  - PURPOSE: In this prospective study we try to evaluate the necessity of performing
      additional transitional zone biopsies as part of the standard sextant biopsies
      procedure in order to detect prostate cancer. MATERIALS AND METHODS: During a 12
      month period we performed biopsies in 420 patients. All patients had two
      additional biopsies of the transitional zone biopsies. 289 of them were biopsies
      for the first time because they had an elevated PSA and/or a suspicious DRE. One
      hundred and thirty-one had a repeat biopsy because of the remaining elevated PSA
      after the previous negative one. RESULTS: Of the 420 patients 143 (34%) had
      cancer, with 11 (7%) having cancer in the transitional zone only. Patients
      initially evaluated because of high PSA and or a positive DRE had only 2 (2.1%)
      cancers exclusively in the transitional zone. We found that this percentage rises
      (18.7%) when the patients had already at least one previous negative biopsy of
      the peripheral zone, and during the repeat biopsy the transitional zone is
      samples. CONCLUSIONS: The low yield of transitional zone biopsies (2.1%) during
      first time sampling of the prostate does not warrant their systematic use for the
      early detection of prostate cancer. Instead the effectiveness of biopsies in that
      area is higher when the biopsy is repeated after an initial previous negative
      biopsy of the peripheral zone.

PMID- 11834904
TI  - Thymidine phosphorylase and dihydropyrimidine dehydrogenase in bladder cancer.
AB  - Thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) levels in
      transitional cell carcinoma of the bladder resected from 38 patients were
      examined by ELISA. TP levels in high-grade and invasive cancer were significantly
      higher than those in low-grade and superficial cancer, respectively. No
      significant differences in the DPD levels were observed among grades and stages,
      but the DPD/TP ratio was significantly lower in grade 3 tumor than in grade 1.
      These results demonstrated that 5'-deoxy-5-fluorouridine seemed to be useful for
      managing patients with grade 3 cancer. The present study also suggested that we
      might be able to exclude cases of bladder cancer in which 5-fluorouracil group
      medicines would be inappropriate candidates in treatment options by measuring
      both TP and DPD levels in the tumor.

PMID- 11834905
TI  - Scrotal cystic hygroma in a 13-year-old boy.
AB  - We describe a patient with cystic hygroma, in a rare location (scrotum). The
      hygroma was diagnosed incidentally after injury to the scrotum in a 13-year-old
      boy. The diagnostic methods used, the characteristics of this type of tumor, its
      treatment and its clinical course are described. We suggest that cystic hygroma
      be taken into account in the differential diagnosis of other more frequent causes
      of scrotal masses.

PMID- 11834906
TI  - Stone granuloma--not to be forgotten as a delayed complication of ureteroscopy.
AB  - Endoscopic management of urolithiasis is one of the commonest urological
      procedures today. Its safety and efficacy in the management of ureteral calculi
      have been proven. A stone granuloma is a rare cause of recurrent ureteral
      obstruction subsequent to ureteroscopic stone removal. After its initial
      description by Dretler and Young [J Urol 1993;150:1800-1802] there have been
      sporadic reports of stone granuloma and paraureteral calculi secondary to
      iatrogenic perforations of the ureter and subsequent ureteric strictures as the
      cause of recurrent ureteral obstruction. We report two cases of delayed stone
      granuloma following pneumatic lithotripsy during ureteroscopy.

PMID- 11834907
TI  - Renal metastasis from squamous cell carcinoma of the hypopharynx.
AB  - We present a rare case of metastatic renal tumor originating from squamous cell
      carcinoma of the hypopharynx. A 67-year-old man treated with irradiation for
      hypopharyngeal carcinoma was referred to our hospital with gross hematuria and a
      left renal mass, which was delineated as a heterogeneously enhanced mass by CT
      scan. Left nephrectomy was performed, and the non-encapsulated mass was gray in
      color macroscopically. Histological examination of the specimen revealed alveolar
      proliferation of small cancer cells, which was consistent with the original tumor
      of the hypopharynx. The left renal tumor was diagnosed as poorly differentiated
      squamous cell carcinoma metastasized from the hypopharynx. The patient remains
      alive, with no evidence of disease, 8 months following left nephrectomy. This
      case was thought to be the first report of a renal metastasis from a
      hypopharyngeal carcinoma that was diagnosed clinically and treated with
      nephrectomy.

PMID- 11834908
TI  - Elevated serum pancreatic enzyme activities in kidney transplant recipients and
      azathioprine drug therapy: is thiopurine methyltransferase polymorphism one
      missing link?

PMID- 11834909
TI  - Women and compliance: the forgotten issues in heart disease prevention.

PMID- 11834910
TI  - Behavioral medicine strategies for heart disease prevention: the example of
      smoking cessation.
AB  - Health related behavior change is one of the most important challenges in the
      prevention of cardiovascular disease. Lifestyle patterns, such as high fat diet,
      lack of exercise, persistent smoking, and poor compliance with prescribed
      medications present the core of this challenge. Conventional wisdom and
      considerable scientific evidence establish that the barriers to health related
      behavior change are many and varied. However, much is also known about methods of
      improving behavioral outcomes. Behavioral medicine strategies incorporate
      fundamental principles of behavior change together with biomedical and
      interpersonal approaches to facilitate successful cardiac risk factor
      modification. Physicians have the most potent opportunity to assist patients with
      health behavior change. Unfortunately, physicians are least familiar with
      behavior change technology and the contemporary physician-patient relationship
      lacks the partnership needed to succeed in these difficult areas. The good news
      is that medical education has begun to incorporate training in behavior change
      and interpersonal effectiveness. A description of the behavioral medicine
      approach to smoking cessation provides an excellent model for a thoughtful and
      practical approach to heart disease prevention in every day practice. (c) 2000 by
      CHF, Inc.

PMID- 11834911
TI  - Lipid lowering strategies in women.
AB  - Hyperlipidemia is one of the major modifiable risk factors for coronary heart
      disease in men and women. There is substantial epidemiological data showing the
      relationship between elevations in total and low-density lipoprotein cholesterol,
      triglycerides and low high-density lipoprotein cholesterol, and coronary heart
      disease in women. Yet hyperlipidemia is undertreated in women. This may be due to
      limited data to support intervention for the primary prevention of coronary heart
      disease, confusion in national guidelines, and inadequate counseling on diet and
      exercise in clinical practice. Lipid levels should be evaluated in women with
      established coronary heart disease, cerebrovascular disease, peripheral vascular
      disease, and diabetes. These women should be targeted for aggressive lipid
      lowering with diet, exercise, and medication. Women with multiple risk factors
      and early family history of coronary heart disease should also be evaluated.
      Asymptomatic young women with elevated or borderline lipids should be counseled
      with regard to lifestyle and behavioral interventions such as diet and exercise.
      (c) 2000 by CHF, Inc.

PMID- 11834912
TI  - Hormone replacement therapy (estrogen and progesterone): is it necessary for
      heart disease prevention? 
AB  - This is a brief review of the rationale for estrogen replacement as prevention of
      coronary artery disease. Epidemiological data suggest that Premarin (0.625 mg)
      together with medroxyprogesterone acetate (2.5 mg) can prevent or delay the onset
      of coronary artery disease in postmenopausal women. The major effects of
      estrogens are: improving the lipid profile by lowering low-density lipoprotein
      and raising high-density lipoprotein; acting on vessel walls to reduce intimal
      damage and plaque formation; dilating vessels by both an endothelial dependent
      and an independent pathway; and acting as an antioxidant, thereby reducing the
      oxidation of low density lipoprotein and increasing the production of nitric
      oxide locally in the blood vessel. Oral estrogens and transdermal estrogens may
      act differently on coagulation factors and lipids. The role of specific estrogen
      receptor modulators as possible treatment for postmenopausal women in part will
      depend on the effect of these drugs in preventing coronary artery disease. The
      specific estrogen receptor modulators decrease low-density lipoprotein and
      prevent triglyceride increases but it is unknown if they have estrogenic effects
      on blood vessel walls. Better compliance with estrogen replacement therapy will
      depend on educating women about their risk of getting coronary artery disease,
      and assisting them in decision making, as well as reducing side effects. The
      Heart and Estrogen/Progestin Replacement Study provides evidence that Prempro
      (Premarin/ medroxyprogesterone acetate) should not be given to someone who
      already has heart disease without careful monitoring. (c) 2000 by CHF, Inc.

PMID- 11834913
TI  - Herbs and dietary supplements in the prevention and treatment of cardiovascular
      disease.
AB  - Herbs and dietary supplements can have significant physiological effects. Garlic
      (Allium sativum) has shown beneficial lipid effects in a majority of trials;
      dried garlic preparations are superior to oil preparations. There is preliminary
      evidence that indicates that hawthorn (Crataegus species) may provide benefits in
      congestive heart failure. Coenzyme Q also may be of benefit in congestive heart
      failure. Although observational studies indicate a protective effect of dietary
      or supplemental vitamin E, controlled trails have not shown a beneficial effect
      on angina and have been mixed on whether supplementation decreases major cardiac
      events. Although several observational studies have noted that fish intake
      protects against cardiovascular disease, prospective studies are less impressive.
      Fish oil supplementation may have a mild beneficial effect on hypertension, but
      there is no effect on total cholesterol levels. Trials are inconsistent on
      whether fish oil reduces restenosis rates following coronary angioplasty.
      Carnitine appears to have beneficial effects on congestive heart failure and
      angina; there is also preliminary evidence that arginine may benefit patients
      with congestive heart failure or angina. Herbs and supplements have been
      associated with adverse effects and interactions; for example, garlic inhibits
      platelet aggregation and can cause significant anticoagulation, and the Chinese
      herb danshen (Salvia miltiorrhiza) appears to potentiate warfarin. Several herbs
      and supplements hold promise as adjuncts in the prevention and treatment of
      cardiovascular disease. There is a need for definitive research on the potential
      risks and benefits of these compounds, including appropriate dosages and
      formulations, and delineation of adverse events and interactions. (c)2000 by CHF,
      Inc.

PMID- 11834914
TI  - High-density lipoprotein and coronary heart disease: lessons from recent
      intervention trials.
AB  - Epidemiologic studies have consistently implicated low plasma high-density
      lipoprotein cholesterol as an important, independent risk factor for the
      development of coronary heart disease. However, clinical trials specifically
      designed to evaluate the role of lipid therapy in patients with low high-density
      lipoprotein cholesterol have only been recently reported. They include two trials
      with angiographic end points, the Lopid Coronary Angiography Trial and the
      Bezafibrate Coronary Atherosclerosis Intervention Trial, and three clinical end
      points trials, the Air Force/Texas Coronary Atherosclerosis Prevention study, the
      Department of Veterans Affairs High-Density Lipoprotein Intervention Trial, and
      the Bezafibrate Infarction Prevention study. These and other trials clearly
      indicate that persons with coronary heart disease and high low-density
      lipoprotein cholesterol (>130 mg/dL [3.36 mmol/L]), with or without low high
      density lipoprotein cholesterol, benefit from statin therapy. The Air Force/Texas
      Coronary Atherosclerosis Prevention study showed that persons at high risk of
      coronary heart disease but without known disease, who have moderate levels of low
      density lipoprotein cholesterol as well as low levels of high-density lipoprotein
      cholesterol, also appear to benefit from statin therapy although the cost
      effectiveness of this approach is unclear. The results from the Department of
      Veterans Affairs High Density Lipoprotein Intervention Trial provide convincing
      evidence that patients without high low-density lipoprotein cholesterol and with
      established coronary heart disease and low high-density lipoprotein cholesterol
      benefit from gemfibrozil. This drug may be particularly beneficial for patients
      who, in addition to low high-density lipoprotein cholesterol, present with other
      features of the metabolic syndrome, such as obesity, glucose intolerance, and
      high triglycerides. Whether other fibrates, niacin, or statins lower coronary
      heart disease risk in persons with low high-density lipoprotein cholesterol in
      the absence of high or moderately high low-density lipoprotein cholesterol is
      unknown. (c)2000 by CHF, Inc.

PMID- 11834915
TI  - Perspectives: Preventive cardiology in the new millennium: a virtual specialty?

PMID- 11834916
TI  - Did you know? AHA Prevention V: broadening the concept of primary prevention.

PMID- 11834917
TI  - HDL cholesterol and triglycerides: emerging, emerging.emerged!

PMID- 11834918
TI  - Symposium introduction. Cardiac exercise and wellness: approaches for the new
      millennium.

PMID- 11834919
TI  - Cardiovascular exercise and wellness. Exercise training for cardiac
      rehabilitation patients: meeting the challenges of the millennium.
AB  - Exercise training for cardiac rehabilitation has evolved over the past decades in
      response to a growing knowledge base in exercise physiology, an expanding
      understanding to the knowledge base of coronary disease, and a change in the
      patients presenting for cardiac rehabilitation. The patient population has
      changed from a post myocardial infarction patient group, to patients who have had
      coronary artery revascularization (coronary artery bypass surgery or percutaneous
      transluminal coronary angioplasty) with the implantation of intraarterial stents.
      Program goals have evolved from enhancing endurance fitness in deconditioned
      patients to initiating the long-term adoption of an active exercising lifestyle
      with the use of strength training to complement endurance training. An increased
      understanding of behavioral issues in the adoption of an active lifestyle will
      influence the evolution of cardiac rehabilitation exercise training. During the
      next several years, it is anticipated that the patient population will change to
      include patients with significant left ventricular systolic dysfunction and
      congestive heart failure. The exercise training programs will then further evolve
      to reflect the successful exercise training formats utilized in the multicenter
      trials of exercise training for patients with congestive heart failure. (c) 2000
      by CHF, Inc.

PMID- 11834920
TI  - How much exercise is enough for the coronary patient?
AB  - Prescribing exercise for cardiac patients is comparable in many ways to
      prescribing medications; that is, one recommends an optimal dosage according to
      individual needs and limitations. For in-patients, simple exposure to orthostatic
      or gravitational stress can obviate much of the deterioration in exercise
      tolerance that normally follows a cardiovascular event or intervention. On the
      other hand, the continuum of exercise therapy for outpatients may range from
      brisk walking to marathon running. Upper body and resistance training also have
      been shown to be safe and effective for clinically stable patients. Moderate
      intensity exercise training can produce beneficial changes in functional
      capacity, cardiac function, coronary risk factors, psychosocial well being, and
      possibly improve survival in patients with coronary artery disease. These
      findings may be especially relevant for the previously sedentary patient, in whom
      the subjective discomfort of vigorous exercise may serve as a deterrent to long
      term compliance with physical training. (c) 2000 by CHF, Inc.

PMID- 11834921
TI  - Safety and efficacy of resistive training in patients with coronary heart
      disease.
AB  - In the past 10 to 15 years, there have been several studies on the acute and
      chronic responses to resistive training in patients with cardiovascular disease.
      As a result, the safety and efficacy of resistive exercise has become more
      evident. Resistive training appears to be safe and effective for promoting
      fitness and improving risk factors in patients with coronary heart disease. This
      review addresses the health and fitness benefits in these patients, the
      established guidelines regarding inclusion and exclusion into programs,
      guidelines for resistive training exercise prescriptions, and how these
      guidelines have evolved in recent years. (c) 2000 by CHF, Inc.

PMID- 11834922
TI  - The role of exercise in type II diabetes mellitus.
AB  - A number of studies have demonstrated a beneficial effect of regular physical
      activity on levels of HgbA(1)C in patients with type II diabetes mellitus,
      largely due to an increase in insulin sensitivity. Benefits are related to short
      term improvements in insulin sensitivity following individual exercise bouts.
      Regular exercise can prevent or delay the onset of type II diabetes in high-risk
      populations. The insulin resistant state is associated with a cluster of
      cardiovascular risk factors all of which improve with regular physical activity.
      Because of the high incidence of occult coronary disease, patients need a
      cardiovascular evaluation when initiating an exercise program. High intensity
      exercise may result in retinal hemorrhage and transient worsening of diabetic
      proteinuria. The most common complication is hypoglycemia. A combination of
      aerobic and light resistance exercise is appropriate. Patients should exercise a
      minimum of three times a week for 30-60 minutes at 50% to 75% of their VO(2max).
      (c) 2000 by CHF, Inc.

PMID- 11834923
TI  - Current concepts in optimum nutrition for cardiovascular disease.
AB  - For the past decade, nutritionists have focused on consensus guidelines (National
      Cholesterol Education Program) to reduce dietary saturated fatty acids,
      cholesterol, and excess body weight. However, researchers are looking at other
      ways that diet may influence the progression of cardiovascular disease, including
      lipoprotein oxidation, thrombosis progression, cardiac arrhythmia, and medication
      interaction. Some areas of investigation include the role of various fatty acids
      and supplements-in the form of vitamins, minerals, herbs, and functional foods-as
      well as traditional foods and diets from other parts of the world. This review
      outlines some of the new and relevant nutritional approaches including: specific
      fatty acids (omega 3, monounsaturated and trans fatty acids), dietary supplements
      (herbs, antioxidants, vitamins C and E, Coenzyme Q10, B vitamins and
      homocysteine, L-arginine, Chinese red yeast rice, garlic, soy, flax seed, and
      dietary fiber), food and drink (tea, nuts, plant-sterol and stanol-ester
      containing spreads, alcohol, and grapefruit juice), and the Mediterranean diet.
      (c) 2000 by CHF, Inc.

PMID- 11834924
TI  - Association between plasma homocysteine and vascular atherosclerotic disease in
      older persons.
AB  - Plasma homocysteine is a risk factor for coronary artery disease, stroke,
      extracranial carotid arterial disease, peripheral arterial disease, and aortic
      atherosclerosis in older persons. Randomized trials are in progress investigating
      whether multivitamin therapy to decrease plasma homocysteine levels will reduce
      the risk for cardiovascular disease. (c) 2000 by CHF, Inc.

PMID- 11834925
TI  - Perspectives: Evaluating the need and potential benefits of testing for plasma
      homocyst(e)ine, an independent risk factor for atherosclerotic disease.

PMID- 11834926
TI  - Calcium, coronary artery disease, and EBCT.

PMID- 11834927
TI  - Premenopausal black women are uniquely at risk for coronary heart disease
      compared to white women.
AB  - Premenopausal black women have a two to threefold greater rate of coronary heart
      disease than premenopausal white women. This study was designed to provide
      greater insight into the reasons for this difference which is currently unclear.
      Coronary heart disease risk factors were compared in 100 black and 100 white,
      healthy premenopausal women, ages 18-45 years, and of relatively advantaged
      socioeconomic status. Compared to white women, black women had a higher body mass
      index (32.0+/-9.2 vs. 29.0+/-9.4 kg/m2, p=0.021), and higher systolic (124+/-17
      vs. 115+/-14 mm Hg, p<0.0001) and diastolic (79+/-14 vs. 75+/-11 mm Hg, p=0.048)
      blood pressures. The mean plasma lipoprotein(a) concentration was markedly higher
      in the black women (40.2+/-31.3 mg/dL) than in the white women (19.2+/-23.7
      mg/dL, p<0.0001). The plasma total homocysteine level was also higher in the
      black women (8.80+/-3.38 vs. 7.81+/-2.58 mmol/L, p=0.013). The black women,
      however, had lower plasma triglyceride levels (0.91+/-0.46 vs. 1.22+/-0.60
      mmol/L, p<0.0001) and a trend toward higher high-density lipoprotein cholesterol
      levels (1.37+/-0.34 vs. 1.29+/-0.31 mmol/L, p=0.064) than the white women. Plasma
      total and low-density lipoprotein cholesterol levels were similar. Black women
      consumed more saturated fat and cholesterol. Rates of cigarette smoking and
      alcohol intake were low and similar between the races. In summary, compared to
      white women, black women had a higher mean body mass index, higher blood
      pressures, higher lipoprotein(a) and plasma total homocysteine levels, and
      greater consumption of saturated fat and cholesterol. The differences in coronary
      risk factors between these two premenopausal groups may explain the higher
      incidence of coronary heart disease in black women. (c) 2000 by CHF, Inc.

PMID- 11834928
TI  - Risk factors for ischemic stroke in older persons in an academic hospital based
      geriatrics practice.
AB  - We performed a retrospective analysis of charts investigating risk factors for
      ischemic stroke in 467 men (mean age 80+/-8 years) and 1444 women (mean age 81+/
      8 years) seen in an academic geriatrics practice. Ischemic stroke was present in
      126 of 467 men (27%) and in 296 of 1444 women (20%) (p=0.003). Stepwise logistic
      regression analysis showed that significant independent risk factors for ischemic
      stroke were age (p=0.005 in men and 0.010 in women, odds ratio=1.04 in men and
      1.03 in women); cigarette smoking (p=0.006, odds ratio=1.7 in women);
      hypertension (p<0.001 in men and women, odds ratio=4.6 in men and 3.9 in women);
      diabetes mellitus (p=0.018 in men and <0.001 in women, odds ratio=1.9 in men and
      2.0 in women); serum low-density lipoprotein cholesterol (p<0.001 in men and
      women, odds ratio=1.02 in men and 1.01 in women); and serum high-density
      lipoprotein cholesterol (p<0.001, odds ratio=0.97 in women). Significant
      independent risk factors for ischemic stroke in both sexes were: age,
      hypertension, diabetes mellitus, and serum low-density cholesterol; and in older
      women: cigarette smoking and serum high-density lipoprotein cholesterol (inverse
      association). (c) 2000 by CHF, Inc.

PMID- 11834929
TI  - Plant stanol ester: review of cholesterol-lowering efficacy and implications for
      coronary heart disease risk reduction.
AB  - Plant stanol ester has been shown in over 20 studies to be an effective and safe
      cholesterol-lowering substance. Randomized, placebo-controlled studies indicate
      that 2-3 g/day of plant stanol ester significantly reduces low-density
      lipoprotein cholesterol levels by about 10%-20%. These results have been
      consistently found in various groups, including young adult and elderly men, pre-
      and postmenopausal women, children with and without familial
      hypercholesterolemia, type II diabetics, and patients with coronary heart
      disease. Plant stanol ester has also been shown to significantly augment the
      cholesterol-lowering effect of statins. No clinically significant adverse effects
      have been detected in studies or in general use in Finland, where foods fortified
      with plant stanol ester have been available since 1995. Results of studies with
      plant stanol ester have important implications for both the clinical and public
      health approaches to coronary heart disease risk reduction. (c) 2000 by CHF, Inc.

PMID- 11834930
TI  - The antilipidemic effects of plain and extended-release niacin.
AB  - The extensive antihyperlipidemic effects of niacin are well known. Cardiac doses
      of niacin are effective in lowering low density lipoprotein, triglyceride, and
      lipoprotein(a) levels and in elevating high density lipoprotein levels. Adverse
      reactions to niacin range from annoying cutaneous flushing to hepatic toxicity. A
      new extended-release form of niacin (Niaspan) has been found to have relatively
      mild hepatic effects. Nighttime dosing of Niaspan appears to attenuate cutaneous
      flushing. Regardless of the form of drug prescribed, patients advised to use
      niacin should be carefully screened and monitored. Adverse effects of niacin are
      emphasized because of their particular importance in the provision of primary
      care. The dosing schedules for both plain niacin and extended-release niacin are
      discussed. (c) 2000 by CHF, Inc.

PMID- 11834931
TI  - Perspectives: Benefits of reducing low-density lipoprotein cholesterol
      concentrations to <100 mg/dL.

PMID- 11834932
TI  - Did you know? Functional foods to lower cholesterol.

PMID- 11834933
TI  - Clinical evaluation of stress: an opinion.

PMID- 11834934
TI  - Lipid risk factor correlates of ischemic heart disease as diagnosed by myocardial
      perfusion scintigraphy.
AB  - Patients with known coronary artery disease frequently change their lifestyles
      (e.g., diet, exercise, and smoking habit) after the diagnosis is made. Such
      changes can alter lipid risk factor levels and obscure etiologic risk factor
      associations with the presence of coronary artery disease. It is therefore
      preferable to determine the contribution of potential risk factors before the
      diagnosis of coronary artery disease has been established. In this trial, we used
      stress nuclear myocardial perfusion imaging to diagnose coronary artery disease
      in patients presenting for evaluation of chest pain. Two groups of age- and sex
      matched patients were identified: a normal group (patients with no evidence of
      coronary artery disease), and an abnormal group (patients whose scans indicated
      the presence of significant coronary artery disease due to either fixed or
      reversible perfusion defects). Blood samples were drawn before scanning and
      analyzed for lipid risk factors. Compared to the normal group, the abnormal group
      had higher levels of triglycerides (189+/-91 vs. 135+/-51 mg/dL, p=0.003), lower
      levels of high-density lipoprotein cholesterol (39+/-9 vs. 45+/-14 mg/dL,
      p=0.037), and higher levels of small, dense low-density lipoprotein (LDL(3))
      (42+/-18 vs. 32+/-13 mg/dL, p=0.007). Total cholesterol, low-density lipoprotein,
      and lipoprotein(a) levels were similar between groups. These findings suggest
      that ischemic heart disease, as assessed by myocardial perfusion scintigraphy, is
      more closely associated with the low high-density lipoprotein/high triglyceride
      syndrome than with increased low-density lipoprotein or total cholesterol levels.
      (c) 2000 by CHF, Inc.

PMID- 11834935
TI  - Prevalence of coronary artery disease, ischemic stroke, and symptomatic
      peripheral arterial disease and of associated risk factors in older men and women
      with and without diabetes mellitus.
AB  - The authors performed a retrospective analysis of the prevalence of coronary
      artery disease, ischemic stroke, and symptomatic peripheral arterial disease and
      of associated risk factors in 99 men (mean age 79+/-8 years) with diabetes
      mellitus vs. 368 men (mean age 81+/-8 years) without diabetes mellitus, and in
      260 women (mean age 80+/-8 years) with diabetes mellitus vs. 1184 women (mean age
      81+/-8 years) without diabetes mellitus. All patients were seen in an academic
      outpatient geriatrics practice. Diabetic men had a higher prevalence of coronary
      artery disease, ischemic stroke, and symptomatic peripheral arterial disease
      (p<0.0001); a higher prevalence of smoking (p=0.023), hypertension (p<0.0001),
      and obesity (p=0.0007); higher levels of serum total and low density lipoprotein
      cholesterol (p<0.0001) and triglycerides (p=0.003); and lower levels of serum
      high density lipoprotein cholesterol (p=0.0001) than men without diabetes
      mellitus. Diabetic women had a higher prevalence of coronary artery disease,
      ischemic stroke, and symptomatic peripheral arterial disease (p<0.0001); a higher
      prevalence of hypertension and obesity (p<0.0001); higher levels of serum total
      and low density lipoprotein cholesterol (p=0.0001) and triglycerides (p=0.005);
      and lower levels of serum high density lipoprotein cholesterol (p=0.0001) than
      women without diabetes mellitus. (c) 2000 by CHF, Inc.

PMID- 11834936
TI  - Accuracy of low load exercise-induced T wave normalization in predicting the
      presence of contractile reserve after an anterior myocardial infarction.
AB  - BACKGROUND AND METHODS. Exercise-induced T wave normalization occurring at a low
      (less-than-or-equal50 watt) workload in infarct-related electrocardiographic
      leads was studied in 30 consecutive patients with a recent transmural anterior
      acute myocardial infarction. Patients underwent both ergometric stress testing
      (within 30 days after the infarction) and low dose dobutamine echocardiography.
      The T wave normalization was considered significant when it occurred in at least
      two infarct-related leads. A significant contractile reserve was considered
      present in an infarcted region when 50% or more of the dyskinetic segments
      functionally improved on exercise during dobutamine infusion. RESULTS. Eighteen
      patients showed exercise-induced T wave normalization (group 1), and 12 patients
      did not (group 2). Myocardial contractile reserve in the infarct area was
      detected in 16 patients of group 1 (88%) and in 3 patients (25%) of group 2
      (p=0.004). The overall sensitivity, specificity, and diagnostic accuracy of T
      wave normalization, as it reflects contractile reserve in the infarct area, were
      84%, 82%, and 83%, respectively. CONCLUSION. Low load exercise-induced T wave
      normalization in infarct-related leads appears to be an accurate marker of
      residual contractile reserve in the infarct area in patients with recent
      transmural acute anterior myocardial infarction. (c) 2000 by CHF, Inc.

PMID- 11834937
TI  - The gap between knowledge and practice in the treatment and prevention of
      cardiovascular disease.
AB  - There is a gap between the current knowledge of the treatment of cardiac
      conditions derived from evidence-based medicine and the widespread application of
      this knowledge. The use of ACE inhibitors for patients with congestive heart
      failure, beta blockers in postmyocardial infarction patients, anticoagulation in
      patients with chronic atrial fibrillation, cholesterol medications for either
      primary or secondary prevention of coronary artery disease, and antihypertensive
      treatment, are of proven benefit, yet all are underutilized by cardiologists, as
      well as other medical practitioners. There is evidence that there are methods to
      improve the prescribing of medication, but further studies are required to
      identify the best ways of doing this. A challenge for the future will be to
      identify and apply the best educational programs to improve the quality and
      efficiency of medical care. (c) 2000 by CHF, Inc.

PMID- 11834938
TI  - Maintaining the endothelium: preventive strategies for vessel integrity.
AB  - The endothelium is a diaphanous membrane, only one cell layer thick, that lines
      all of our blood vessels. Despite its apparent fragility, it exerts profound
      control over vascular tone, structure, and interaction with circulating blood
      elements. One of the factors that the endothelium synthesizes is nitric oxide,
      which is the most potent endogenous vasodilator known. In addition to its blood
      flow regulating effects, nitric oxide also inhibits key processes in
      atherosclerosis, including monocyte adherence, platelet aggregation, and
      proliferation of vascular smooth muscle cells. Nitric oxide synthesis is
      impaired, and its degradation is accelerated, in many of the conditions
      associated with atherosclerosis, including hypercholesterolemia. Restoration of
      nitric oxide synthesis and activity in these disorders can improve blood flow,
      relieve symptoms, and perhaps reduce the progression of atherosclerosis (part 1
      of 2 parts). (c) 2000 by CHF, Inc.

PMID- 11834939
TI  - Perspectives: Oral anticoagulant therapy: current issues.

PMID- 11834940
TI  - Did you know? Clinical implications of exercise-induced ventricular arrhythmias.

PMID- 11834941
TI  - VPAC1 is a cellular neuroendocrine receptor expressed on T cells that actively
      facilitates productive HIV-1 infection.
AB  - OBJECTIVE: A lack of productive HIV-1 infection of Kit225 compared to Jurkat T
      cells, despite similar levels of CD4 and HIV-1 chemokine co-receptors, was found
      to correlate with the expression of vasoactive intestinal peptide/pituitary
      adenylate cyclase activating polypeptide receptor-1 (VPAC1). We therefore
      examined a role for this seven-transmembrane G protein-coupled neuroendocrine
      receptor in modulating HIV-1 infection. METHODS: Reverse transcription-PCR was
      used to show the level of VPAC1 expression in different T-cell lines. A signal
      blocking antibody to VPAC1 was used to examine its inhibiting effect on HIV-1
      infection. Transfection of VPAC1 cDNA in both sense and anti-sense orientation
      was used to assess the role of VPAC1 in HIV-1 infection. HIV-1 infection was
      monitored by gag p24 ELISA using HIV-1IIIB or by luciferase activity using pseudo
      envelope-typed HXB2-NL4-3-luciferase. Analysis of HIV-1 gag DNA and 2-LTR circles
      was utilized to examine a possible mechanism for the effect of VPAC1. RESULTS:
      Using VPAC1 signal blocking antibody, we showed that up to 80% of productive
      infection with HIV-1IIIB was inhibited. We also demonstrated that HIV-1 gp120 has
      sequence similarity to the natural ligand for VPAC1 and postulate that it can
      activate this receptor directly. Transfection of VPAC1 cDNA in the anti-sense
      orientation resulted in a significant loss, up to 50% of productive infection. In
      contrast, transfection of cells with VPAC1 in the sense orientation increased the
      productive infection by more than 15-fold and caused a profound increase in
      syncytium formation. Furthermore, stimulation of VPAC1 on primary cells
      facilitated in vitro infection with HIV-1 HXB2-NL4-3. Analysis of HIV-1 gag DNA
      indicated that VPAC1 does not affect viral entry; however, cells that show
      negligible expression of VPAC1 may not be productively infected as indicated by a
      lack of 2-LTR circle formation. CONCLUSION: We have discovered a cellular
      receptor, VPAC1, that is a novel and potent facilitator of HIV-1 infection and
      thus, is a potentially important new target for therapeutic intervention.

PMID- 11834942
TI  - Important contribution of p15 Gag-specific responses to the total Gag-specific
      CTL responses.
AB  - OBJECTIVES: HIV-1 p15 Gag and its protease cleavage products, NCp7 and p6, are
      believed to play a major role in viral infectivity and assembly during the early
      and late stages of the retroviral life cycle. However, the extent to which p15
      Gag is targeted by the host immune system in natural infection as well as precise
      cytotoxic T lymphocyte (CTL) epitopes within this protein remains to be defined.
      METHODS: In this study, 57 HIV-1 infected individuals and 10 HIV-1 negative
      controls were screened for CD8 and CD4 T-cell responses using overlapping
      peptides spanning the entire p15 Gag protein as well as the p17 Gag and p24 Gag
      proteins. Peptide-specific interferon-gamma production was measured by Elispot
      assay and flow-based intracellular cytokine quantification, and cytotoxic
      activity was confirmed after isolation of peptide-specific CD8 T-cell lines.
      RESULTS: CD8 T lymphocytes specific to p15 Gag were found in 46% (26/57) of HIV-1
      infected individuals studied and contributed on average 17% (range, 0-100%) to
      the total Gag-specific T-cell responses. Responses were clustered within three
      immunodominant regions of p15 Gag, mapping to important functional sites. These
      studies also include the description of the first three optimally defined CTL
      epitopes within p15 Gag. CONCLUSIONS: These results indicate that p15 Gag is
      frequently recognized by HIV-1-specific CD8 T cells in HIV-1 infection and will
      be important in the comprehensive assessments of CTL responses in infected
      persons, as well as the design and testing of future HIV-1 vaccines and
      immunotherapeutic interventions.

PMID- 11834943
TI  - Lack of control of T cell apoptosis under HAART. Influence of therapy regimen in
      vivo and in vitro.
AB  - BACKGROUND: Increased and premature T cell apoptosis is recognized as a feature
      of HIV infection, and its normalization during highly active antiretroviral
      therapy (HAART) is thought to contribute to quantitative CD4 T cell restoration.
      DESIGN: Cross-sectional study of spontaneous, CD3- and CD95-mediated apoptosis in
      lymphocytes from 53 HIV-infected individuals taking HAART. METHODS: Overnight
      stimulation of peripheral blood mononuclear cells (PBMC) with coated anti-CD3 or
      anti-CD95 monoclonal antibodies or incubation overnight in medium. Apoptosis in
      CD4 and CD8 T cells was measured by flow cytometry. For in vitro assay of
      antiretroviral drugs, normal PBMC were prestimulated with anti-CD3 monoclonal
      antibodies and apoptosis was induced by ligation of CD95. The expression of
      active caspase-8 and caspase-3 was examined by flow cytometry. RESULTS: We report
      for the first time that important levels of T cell apoptosis may persist under
      HAART, in spite of a rise in CD4 T cells from baseline and a sustained
      suppression of plasmatic viral load. Spontaneous CD3- or CD95-induced apoptosis
      levels were inversely correlated with the in vivo number of CD4 T cells and the
      CD4/CD8 ratio, but not with the viral load or duration of antiretroviral therapy.
      Regimens including lamivudine are associated with persistent T cell apoptosis,
      particularly following CD95 ligation. Lamivudine was also found to stimulate in
      vitro CD95-induced apoptosis and caspase activation in pre-activated T
      lymphocytes from healthy donors. CONCLUSION: The immunomodulatory effect of
      lamivudine may be one of the contributing factor to increased levels of T cell
      apoptosis under HAART. The data suggest that there is a requirement for
      physiological apoptosis during HAART.

PMID- 11834944
TI  - Effect of target cell availability on HIV-1 production in vitro.
AB  - OBJECTIVE: The recovery of CD4 target cells following antiretroviral therapy may
      facilitate virus production and escape from antiretroviral suppression. To
      address this hypothesis, we directly examined whether the CD4 target cell number
      increases viral production in the presence of suboptimal therapy. DESIGN: The
      effect of the CD4 T cell number on HIV-1 replication with a suboptimal dose of
      zidovudine was studied in vitro. METHODS: Varying numbers of CD4 T cells were
      infected with HIV-1 and treated with 1 nM zidovudine. Virus production was
      measured by p24 antigen capture enzyme-linked immunosorbent assay. Partial
      sequencing of HIV-1 pol was performed to assess zidovudine-resistant mutations.
      RESULTS: Wild type virus production was found to increase eightfold in cultures
      with 100 x 10(4) cells compared with cultures with 10 x 10(4) cells. The IC90 of
      zidovudine was 4 logs higher in cultures with 16 x 10(4) cells compared with
      cultures with 1 x 10(4) cells. No zidovudine-resistant mutations were found.
      CONCLUSION: Target cell availability may play a direct role in wild type HIV-1
      resurgence following therapy.

PMID- 11834945
TI  - Monocytes and T lymphocytes in HIV-1-positive patients express HLA-G molecule.
AB  - OBJECTIVE: To study the expression of HLA-G on peripheral blood mononuclear cells
      (PBMC) from HIV-1-infected individuals in order to determine whether this
      molecule is induced as a consequence of HIV-1 infection. DESIGN: A total of 23
      HIV-positive individuals in different stages of the disease were studied.
      METHODS: Flow cytometric analysis and Western blot were used to measure HLA-G
      expression on PBMC obtained from HIV-positive and control individuals. RESULTS:
      Most of the monocytes obtained from HIV-1-infected individuals express HLA-G,
      whereas only a very low proportion of monocytes from healthy individuals express
      this molecule. When T lymphocytes from HIV-1 infections were studied, it was
      found that 30% of them express HLA-G, whereas only 1% were HLA-G-positive in
      healthy individuals. HLA-G expression was also confirmed by Western blot using
      specific anti-HLA-G monoclonal antibodies. CONCLUSION: The synthesis of HLA-G is
      increased in monocytes and certain T lymphocytes from HIV-1-infected individuals.

PMID- 11834946
TI  - CD36 deficiency induced by antiretroviral therapy.
AB  - BACKGROUND: The molecular basis of lipodystrophy, a syndrome associated with HIV
      antiretroviral (ARV) therapy, remains unknown. OBJECTIVES: To examine whether ARV
      therapy might inhibit the expression of CD36, which is known to play an important
      role in fatty acid and glucose metabolism, and if this might contribute to the
      metabolic alterations associated with lipodystrophy. DESIGN: The effects of ARV
      therapy on CD36 levels was examined in vivo in a prospective cohort of
      individuals treated with ARV therapy and in vitro in assays of human cell lines
      exposed to ARV drugs. METHODS: Monocyte CD36 levels were assessed by flow
      cytometry at baseline and after 7 days of therapy in five healthy volunteers and
      10 treatment-naive HIV-1-infected individuals. ARV therapy included protease
      inhibitors (ritonavir, nelfinavir or lopinavir/ritonavir). In addition, human
      cell lines (THP-1 and C32) were assessed for CD36 levels pre and post-ritonavir
      treatment. RESULTS: Three of four healthy controls (one withdrew because of
      adverse effects) and 6 of 10 HIV-1-infected individuals had a 50 to > 90%
      decrease in monocyte CD36 levels after 7 days of therapy. One of ten HIV-infected
      subjects had a 30% decrease, and the remaining individuals had no change or an
      increase in CD36 levels. CD36 levels decreased significantly in human cell lines
      treated with ritonavir but not in those treated with zidovudine. CONCLUSIONS: ARV
      therapy resulted in a marked decrease in CD36 in approximately 70% of our
      participants. Sustained ARV therapy-induced CD36 deficiency may contribute to
      insulin resistance and other metabolic complications of lipodystrophy.

PMID- 11834947
TI  - The extent of HIV-1-related immunodeficiency and age predict the long-term CD4 T
      lymphocyte response to potent antiretroviral therapy.
AB  - OBJECTIVE: To study the long-term immunological recovery in HIV-1-infected
      individuals receiving potent antiretroviral therapy (ART). DESIGN: Prospective,
      observational study. METHODS: Plasma HIV-1 RNA, CD4 and CD8 T lymphocyte counts
      were determined at 3-6 monthly intervals in 95 HIV-1-infected subjects receiving
      ART who suppressed plasma HIV-1 RNA to levels below 400 copies/ml during a median
      observation period of 45 months. RESULTS: The median CD4 cell count rose from 325
      to 624 cells/microl at 48 months, increasing by 22.6 cells/microl per month in
      the first 3 months, 8.1 cells/microl per month from months 3 to 12, 6.8
      cells/microl per month in the second year, 3.3 cells/microl per month in the
      third, and 1.7 cells/microl per month in the fourth year. At 48 months, 98% of
      subjects reached CD4 cell counts > 200 cells/microl, 86% > 350 cells/microl, and
      74% > 500 cells/microl. A higher nadir CD4 cell count and younger age were
      independently associated with greater increases in CD4 cell counts, and higher
      absolute CD4 cell counts at 48 months. Poor immunological responders who did not
      reach 500 CD4 lymphocytes/microl at 48 months showed lower nadir and baseline CD4
      cell counts than good responders (99 versus 300 cells/microl and 160 versus 373
      cells/microl, respectively). CONCLUSION: The recovery of CD4 T lymphocytes occurs
      mainly in the first 2 years after the initiation of ART, and is associated with
      age and the pre-existing degree of HIV-1-related immunodeficiency, suggesting
      that the long-term exposure to HIV-1 infection has caused damage to the immune
      system that is difficult to correct.

PMID- 11834948
TI  - Usefulness of monitoring HIV drug resistance and adherence in individuals failing
      highly active antiretroviral therapy: a randomized study (ARGENTA).
AB  - OBJECTIVE: To establish the influence of genotypic resistance-guided treatment
      decisions and patient-reported adherence on the virological and immunological
      responses in patients failing a potent antiretroviral regimen in a randomized,
      controlled trial in a tertiary care infectious diseases department. PATIENTS: A
      total of 174 patients with virological failure were randomly assigned to receive
      standard of care (SOC) or additional genotypic resistance information (G).
      Adherence was measured by a self-administered questionnaire. MAIN OUTCOMES
      MEASURES: Primary endpoints were the proportion with HIV-RNA < 500 copies/ml at 3
      and 6 months by intention-to-treat analysis. Secondary endpoints were changes
      from baseline HIV-RNA levels and CD4 cell counts. RESULTS: At entry, 25% had
      failed three or more highly active antiretroviral therapy (HAART) regimens and
      41% three drug classes; there were more resistance mutations in G. In 127
      evaluable questionnaires, 43% reported last missed dose during the previous week.
      At 3 months, 11 of 89 patients (12%) in SOC and 23 of 85 (27%) in G had HIV-RNA <
      500 copies/ml (OR 2.63, 95% CI 1.12-6.26); the relative proportions were 17 and
      21% at 6 months. CD4 cell changes did not differ between arms. Six month CD4 cell
      changes were +62 in adherent and -13 cells/microl in non-adherent patients (P <
      0.01). Being assigned to G, good adherence, previous history of virological
      success, fewer experienced HAART regimens and lower baseline viral load were
      independently predictive of 3 month virological success. CONCLUSION: The
      virological benefit of genotype-guided treatment decisions in heavily pre-exposed
      patients was short term. Patients adherence and residual treatment options
      influenced outcomes.

PMID- 11834949
TI  - Switching from protease inhibitors to efavirenz: differences in efficacy and
      tolerance among risk groups: a case-control study from the Swiss HIV Cohort.
AB  - OBJECTIVES: Many patients have simplified their therapy by replacing protease
      inhibitors (PI) with efavirenz. In a large cohort study representative of
      clinical practice, we compared outcomes in patients who replaced PI with
      efavirenz (switchers), with patients who continued on PI (non-switchers). We
      investigated the likelihood of virological failure in switchers and non
      switchers, and the tolerance of efavirenz-containing regimens in different
      transmission risk groups. DESIGN, SETTING, AND METHODS: Using the database of the
      Swiss HIV Cohort Study, we identified patients who switched from PI-containing to
      efavirenz-containing highly active antiretroviral therapy for reasons of
      tolerance, toxicity, or convenience. Switchers were matched to non-switchers on
      the basis of calendar time, CD4 cell count, and viral load. RESULTS: The
      probability of virological failure was less in patients who switched to efavirenz
      values after one year: 9.4% [95% confidence interval (CI) 5.5-15.9] versus 27.2%
      (95% CI 21.5-34.1), odds ratio (OR) for failure 0.34. The effect was more
      pronounced when injection drug users (IDU) were omitted from the analysis (OR
      0.19, 95% CI 0.09-0.43); it was absent in IDU (OR 0.95, 95% CI 0.44-2.04). IDU
      stopped efavirenz more frequently during the first 2 months of treatment than non
      IDU [22.6% (95% CI 11.5-41.6) versus 6.6% (95% CI 3.6-11.8) at 2 months]. No
      difference between IDU and non-IDU was evident when the frequency of stopping
      indinavir or nelfinavir was measured. CONCLUSION: Switchers had less virological
      failure and less chance of further treatment changes than non-switchers. However,
      efavirenz was less successful in IDU than in other transmission categories.

PMID- 11834951
TI  - Post-exposure prophylaxis after non-occupational HIV exposure: impact of
      recommendations on physicians' experiences and attitudes.
AB  - OBJECTIVE(S): To evaluate the impact of official recommendations for non
      occupational HIV post-exposure prophylaxis (PEP), issued in France in 1998, on
      physicians' prescriptions and attitudes and the occurrence of severe PEP side
      effects. DESIGN: Two surveys were carried out among hospital physicians involved
      in HIV care, before (1997) and after (1999) the publication of recommendations.
      METHODS: Questionnaires explored, for the last 12 months, description of PEP
      requests and prescriptions, detailed description of the latest treated exposure,
      prescription attitudes towards five exposure scenarios and types of severe side
      effects of antiretroviral drugs (in 1999 only). RESULTS: Nationally, from 1997 to
      1999, PEP requests and prescriptions increased sevenfold and ninefold,
      respectively. Most requests followed sexual exposure (71% in 1997 and 86% in
      1999; P = 10(-6)). The proportion of prescriptions for exposure to a known HIV
      infected person decreased from 78% in 1997 to 41% in 1999 (P = 10(-6)). Three
      drug combination therapies increased from 46% in 1997 to 83% in 1999 (P = 10(
      6)). In 1999, 13 (0.9%; 95% confidence interval, 0.5-1.5%) severe reversible
      adverse events occurred among patients on a three-drug regimen. Prescription
      attitudes based mainly on risk assessment in 1997 (64% versus 33% in 1999) were
      based mainly on the request of the patient in 1999 (41% versus 11% in 1997).
      CONCLUSION: Recommendations were followed by an increase of PEP, particularly
      after less risky exposures, and a substantial risk of severe side-effects. PEP
      should be restricted to well-documented exposures for which the risk of
      transmission outweighs the risk of severe side-effects. Drug regimens should be
      revised.

PMID- 11834950
TI  - HIV-1 genotype and phenotype correlate with virological response to abacavir,
      amprenavir and efavirenz in treatment-experienced patients.
AB  - OBJECTIVE: To assess the safety and efficacy of three new drugs in patients with
      antiretroviral failure and to correlate retrospectively baseline factors with
      virological response. DESIGN AND SETTING: Open-label, 48-week, single-arm, multi
      center phase II trial conducted at nine US university or government clinics and
      private practices. PATIENTS AND INTERVENTIONS: Patients with HIV-1 RNA > or =500
      copies/ml despite > or =20 weeks of treatment with at least one protease
      inhibitor received abacavir 300 mg twice a day, amprenavir 1200 mg twice a day
      and efavirenz 600 mg once a day. Other antiretrovirals were prohibited until week
      16 except for substitutions for possible abacavir hypersensitivity. MAIN OUTCOME
      MEASURES: HIV RNA at weeks 16 and 48. RESULTS: A total of 101 highly treatment
      experienced patients enrolled; 60 were naive to non-nucleoside analog reverse
      transcriptase inhibitors (NNRTI). HIV RNA < 400 copies/ml was attained in 25 out
      of 101 (25%) patients at 16 weeks (35% of NNRTI-naive and 10% of -experienced
      patients) and 23 (23%) patients at 48 weeks (33% of naive and 7% of experienced
      patients). CD4 cells increased by a median of 15 x 10(6) and 43 x 10(6) cells/l
      at weeks 16 and 48, respectively. Drug-related rash occurred in 50 out of 99
      (51%) of patients, and 17 out of 99 (17%) permanently discontinued one or more
      drugs as a result. Lower baseline viral load, fewer NNRTI-related mutations,
      absence of decreased abacavir (> or =4-fold) and efavirenz (> or =10-fold)
      susceptibility, and greater number of drugs to which virus was susceptible were
      associated with virological response at week 16. CONCLUSIONS: Abacavir,
      amprenavir and efavirenz durably reduced HIV RNA and increased CD4 cell counts in
      a subset of treatment-experienced adults. Baseline viral load and some genotypic
      and phenotypic markers of resistance correlated with HIV RNA response.

PMID- 11834952
TI  - Severity of HIV-associated neuropathy is associated with plasma HIV-1 RNA levels.
AB  - OBJECTIVE: To determine if there is an association between plasma HIV-1 RNA
      levels and severity of HIV-associated distal symmetrical polyneuropathy (DSP).
      DESIGN: Substudy of AIDS Clinical Trials Group Protocol 291, a double-blind,
      placebo-controlled study of recombinant human nerve growth factor for the
      treatment of painful DSP. METHODS: Two-hundred and thirty-six subjects had plasma
      HIV-1 RNA load assayed at baseline. Mean and maximum neuropathic pain was
      assessed once daily by the Gracely Pain Scale. Other measures included subjects'
      global pain assessment and quantitative sensory tests (QST). These values were
      correlated with baseline HIV-1 RNA levels. RESULTS: Among 168 subjects with
      detectable plasma HIV-1 RNA, there was a significant correlation between plasma
      HIV-1 RNA and the severity of maximum and global pain, and toe cooling
      thresholds. Maximum and global pain assessment correlated with plasma HIV-1 RNA
      in individuals with detectable viral load (r, 0.162 and 0.194; P = 0.04 and 0.01,
      respectively). CONCLUSIONS: There is an association between plasma HIV-1 RNA
      levels and the severity of pain and QST results in HIV-associated DSP. Further
      studies are needed to determine if aggressive use of antiretroviral drugs,
      including the use of dideoxynucleosides, may be of benefit to prevent or improve
      peripheral neuropathy.

PMID- 11834953
TI  - Granulocyte-macrophage colony-stimulating factor enhances viral load in human
      brain tissue: amelioration with stavudine.
AB  - BACKGROUND: Granulocyte-macrophage colony-stimulating factor (GM-CSF) is elevated
      in cerebrospinal fluid in HIV- associated dementia; in addition, therapeutic GM
      CSF elevates plasma viral load. OBJECTIVE: To assess the effect of GM-CSF on
      viral replication and the potential ameliorative effect of antiretroviral
      therapy. DESIGN: A primary human brain aggregate system is used as a model of the
      in vivo situation. METHOD: Cultured aggregates were infected with the macrophage
      tropic strain HIV-1SF162 and then exposed to varying GM-CSF concentrations and
      0.3 micromol/l stavudine. Viral replication was assessed by p24 expression in the
      supernatant and aggregates. Immunohistochemistry identified neurons, astrocytes,
      microglia and oligodendrocytes. RESULTS: A GM-CSF concentration of 1 ng/ml
      resulted in a fivefold increase in microglial cells, the main HIV cellular
      reservoir (P = 0.0001). Prior GM-CSF exposure before infection of the aggregates
      resulted in sixfold increase in p24 levels compared with non-GM-CSF-exposed
      infected aggregates. Infected aggregates with or without GM-CSF had significant
      neuronal loss of 50% and 45%, respectively, and astrocytosis. Addition of
      stavudine to the infected aggregates, even in the presence of GM-CSF, reduced p24
      levels to zero and prevented neuronal loss and astrocytosis. CONCLUSIONS: This
      study demonstrates that GM-CSF enhances viral replication while addition of
      stavudine prevents this potentially detrimental process.

PMID- 11834955
TI  - Assessing the utility of five domains in SF-12 Health Status Questionnaire in an
      AIDS clinical trial.
AB  - OBJECTIVE: To assess a shortened quality-of-life (QoL) measurement tool in a
      population with advanced HIV infection. DESIGN: Five domains (seven items) in a
      12-item questionnaire (SF-12) were compared with those same domains in a 39-item
      questionnaire (SF-39). Data were collected using SF-39 in a randomized clinical
      trial for the prevention of cytomegalovirus disease. METHODS: The performance of
      SF-12 relative to SF-39 was evaluated within each domain by comparing QoL scores
      at baseline and over time, assessing the reliability and validity for both
      instruments, assessing item consistency and discrimination within instruments,
      and implementing event-time analyses that quantified dependence of the hazard for
      death and progression of disease (POD) on baseline values. RESULTS: Baseline
      measures are similar for both instruments, with high correlation within each
      domain. The slopes over time for the SF-12 and SF-39 domains are also similar.
      Both the SF-12 and SF-39 domains have satisfactory reliabilities and perfect
      discrimination. The hazard ratios for death and POD are similar for both
      instruments within a domain. All SF-12 and most SF-39 domains are highly
      predictive for death but are not highly predictive for POD. CONCLUSIONS: For the
      domains considered, SF-12 is a reasonable and effective replacement for SF-39 in
      studies of patients with advanced HIV disease. SF-12 reduces item redundancy and
      the burden of data requirements for both investigators and patients;
      consequently, it may improve compliance with form completion.

PMID- 11834954
TI  - Antitumor activity of oral 9-cis-retinoic acid in HIV-associated Kaposi's
      sarcoma.
AB  - OBJECTIVE: To assess the efficacy, safety and tolerance of oral 9-cis-retinoic
      acid in HIV-infected patients with Kaposi's sarcoma. METHODS: Sixty-six patients
      with AIDS-related Kaposi's sarcoma were enrolled at 14 centers; 60 received the
      study medication and were analyzed and, of these, 45 (75%) had received prior
      therapy for Kaposi's sarcoma. Once daily oral 9-cis-retinoic acid (alitretinoin,
      Panretin) was administered at doses up to 140 mg/m2. Most patients (72%) received
      a maximum dose of 100 mg/m2. Response was assessed using AIDS Clinical Trials
      Group (ACTG) criteria. RESULTS: The median age was 38 years and the median
      absolute CD4 cell count was 194 x 10(6) cells/l (range 6-784 x 10(6)). Despite
      the use of three- and four-drug antiviral regimens (83%), the median HIV RNA at
      baseline was 8701 copies/ml [range < 500 (lower limit of detection) to 4.24 x
      10(6)]. The tumor response rate was 37% (95% confidence interval 25-49). Tumor
      response was associated with improved quality-of-life measures. There was a
      significant increase in interleukin 6 (IL-6) levels from baseline to week 4.
      Responders had significantly lower baseline soluble IL-6 receptor levels (P =
      0.029) than non-responders. The median time to response was 9 weeks (mean, 13
      weeks; range, 4-36). HIV RNA levels did not change significantly during therapy
      nor did they correlate with tumor responses. Study drug was discontinued by 28
      patients for adverse events, which included headache (13) and skin toxicity (10).
      CONCLUSION: Oral 9-cis-retinoic acid is an active antitumor drug for AIDS-related
      Kaposi's sarcoma. Treatment is associated with skin and constitutional toxicity
      and further studies are needed to improve its long-term tolerance.

PMID- 11834956
TI  - HIV coinfection does not compromise liver histological response to interferon
      therapy in patients with chronic hepatitis C.
AB  - OBJECTIVE: Although discrepancies between histological and virological responses
      to anti-hepatitis C virus (HCV) therapy are well-established in HIV-negative
      patients, the liver histological outcome has never been assessed in HIV-HCV co
      infected patients receiving anti-HCV therapy. We compared histological responses
      to interferon (IFN) alpha therapy between HIV-positive and HIV-negative injecting
      drug users (IDU) and determined factors associated with histological response.
      DESIGN: Retrospective cohort study. SETTING: Hepatology unit of a tertiary
      referral hospital. PATIENTS/INTERVENTIONS: Seventy-nine HCV-infected IDU (32 HIV
      positive) receiving a 6-month course of IFN-alpha2b therapy, 3 x 106 U three
      times a week. PRIMARY OUTCOME MEASURE: Histological response, defined by a > or
      =2 point decrease in total Knodell score measured on paired liver biopsies over a
      2-year follow-up period. RESULTS: The sustained response rate to IFN therapy was
      lower in HIV-positive patients than in HIV-negative patients (6.2% versus 29.8%;P
      = 0.012). Conversely, the rates of histological response (40.6% versus 36.2%)
      were not different between HIV-positive and HIV-negative patients. Independent
      factors associated with histological response were first total Knodell score (P =
      0.0007) and sustained response to IFN therapy (odds ratio, 12.34; P = 0.005).
      Histological response was observed in 25% of IFN non-responders whatever their
      HIV status. In HIV-positive patients, the CD4 cell count did not influence the
      histological response. CONCLUSIONS: in HIV-HCV co-infected patients treated with
      IFN, liver histological improvement is frequently observed, similarly to that
      observed in HIV-negative patients. Such beneficial effect of interferon therapy
      supports early treatment of chronic hepatitis C in HIV-infected patients.

PMID- 11834957
TI  - Combined surgery and cidofovir is an effective treatment for genital warts in HIV
      infected patients.
AB  - OBJECTIVE: To evaluate the efficacy of surgical-cidofovir (SCT), surgical (ST)
      and cidofovir (CT) treatment of genital warts in HIV-infected patients. DESIGN:
      Open randomized prospective pilot study. SETTING: Outpatients attending the
      sexually transmitted disease service of the II Dept of Infectious Diseases, L
      Sacco Hospital, Milan-Italy. PATIENTS: Consenting HIV-positive patients with anal
      genital warts recruited from January 2000 to March 2001. INTERVENTIONS: Three
      treatment arms: surgical excision by electrocautery, topical 1% cidofovir-gel (5
      days per week, maximum 6 weeks) and electrocautery-cidofovir treatment with 1%
      cidofovir-gel applied within 1 month of surgical treatment (5 days per week for 2
      weeks). MAIN OUTCOME MEASURES: Rate of wart clearance and time and rate of
      relapses within a 6-month follow-up period. RESULTS: Complete response was
      achieved in 93.1% of 29 patients treated by ST, 76.2% of 26 treated by CT and in
      100% of 19 patients treated by SCT (P = 0.0033). The relapse rate in 49 patients
      followed-up was 73.68% in ST, 35.29% in CT and 27.27% in SCT patients (P =
      0.018). Median time to relapses in ST patients was 66 days (Kaplan-Meyer, P =
      0.0012). Human papillomavirus DNA was cleared in 52.63% of 19 patients evaluated.
      The rate of clearance of high risk and low risk genotypes was 0% and 57.14% 25%
      and 50% 100% and 71.42% in ST, CT and SCT patients, respectively. CONCLUSIONS: A
      combination of surgical and medical treatment was most effective in clearing
      lesions completely and in reducing the relapse rate. Human papillomavirus DNA
      clearance can be attributed to the antiviral effect of cidofovir and could
      explain the low relapse rate observed. Larger studies are required to determine
      the most appropriate medical treatment for viral eradication after surgery.

PMID- 11834958
TI  - Herpes simplex virus type 2 infection increases HIV incidence: a prospective
      study in rural Tanzania.
AB  - OBJECTIVES: To quantify the association between prevalent or incident Herpes
      simplex virus type-2 (HSV2) infection and the incidence of HIV seroconversion
      among adults in the general population in rural Tanzania. STUDY POPULATION:
      Adults aged 15-54 years sampled randomly from 12 rural communities in Mwanza
      Region, Tanzania and recruited to a randomized trial of improved treatment of
      sexually transmitted diseases. STUDY DESIGN: Unmatched case-control study nested
      within trial cohort. METHODS: Participants included 127 cases who seroconverted
      to HIV during the 2-year follow-up period and 636 randomly selected controls who
      remained HIV negative. Subjects were tested for HSV2 serology at baseline and
      follow-up, and associations between HIV and HSV2 were analysed with adjustment
      for socio-demographic and behavioural factors. RESULTS: After adjusting for
      confounding factors, a strong association between HSV2 infection and HIV
      seroconversion was observed in men (test for trend: P < 0.001), with adjusted
      odds ratios (OR) of 6.12 [95% confidence interval (CI), 2.52-14.9] in those HSV2
      positive at baseline, and 16.8 (95% CI, 6.06-46.3) in those acquiring HSV2
      infection during follow-up. A weaker association was observed in women (tests for
      trend: P = 0.14), with adjusted OR of 1.32 (95% CI, 0.62-2.78) and 2.36 (95% CI,
      0.81-6.84), respectively. Population attributable fractions of incident HIV
      infection due to HSV2 were estimated as 74% in men and 22% in women. CONCLUSIONS:
      The results suggest that HSV2 plays an important role in the transmission of HIV
      infection in this population. There is an urgent need to identify effective HSV2
      control measures in order to reduce HIV incidence in Africa.

PMID- 11834959
TI  - Decline in the prevalence of HIV and sexually transmitted diseases among female
      sex workers in Cotonou, Benin, 1993-1999.
AB  - BACKGROUND: Within an ongoing HIV/STD prevention project aimed at female sex
      workers (FSW) in Cotonou, Benin, we evaluated time trends in HIV and STD
      prevalences from 1993 to 1999. DESIGN: Three serial cross-sectional surveys were
      conducted in 1993 (n = 374), 1995-1996 (n = 365), and 1998-1999 (n = 591). A
      questionnaire was administered to the FSW and they were screened for HIV,
      syphilis, Neisseria gonorrhoeae, and Chlamydia trachomatis. RESULTS: The mean
      percentage of condom use with clients in the week preceding the interview
      increased from 62.2% in 1993 to 80.7% in 1998-1999 (P = 0.0001). The prevalence
      of all infections decreased significantly (all P < 0.02; chi-square for trend)
      over time: HIV from 53.3% in 1993 to 40.6% in 1998-1999; syphilis from 8.9 to
      1.5%; gonorrhoea from 43.2 to 20.5%; and chlamydia from 9.4 to 5.1%. However, the
      mean age of FSW decreased from 31.0 to 28.4 years between 1993 and 1998-1999.
      Moreover, the country of origin of these women changed dramatically over time:
      the proportion of Ghanaian women decreased from 66.3% in 1993 to 21.6% in 1998
      1999 when the predominant group became Nigerian (38.0%). When controlling for age
      and country of origin, HIV prevalence was stable over time (P = 0.71), whereas
      the downward trend remained significant for syphilis and gonorrhoea (both P <
      0.001), and was present but not significant for chlamydia (P = 0.13). CONCLUSION:
      These data suggest that the time trends in HIV and STD prevalences are partly due
      to the changing sex work milieu, but that the intervention also had an impact.
      Prevention programmes aimed at FSW should be highly prioritized.

PMID- 11834960
TI  - Pregnancy and birth rates among HIV-infected women in the United States: the
      confounding effects of illicit drug use.
AB  - OBJECTIVE: To determine the effect of HIV infection on pregnancy and birth rates
      and assess the potentially confounding effect of illicit drug use. DESIGN: A
      retrospective record review of matched cohorts examining pregnancy outcomes for
      HIV-positive women and two HIV-negative comparison groups (one matched by drug
      use). METHODS: Ninety HIV-positive women who gave birth in a US city between 1989
      and 1993 were matched to HIV-negative women by race, age, parity and date of
      index birth (group 1, N = 180) and also by the type of illicit drug used (group
      2, N = 90). Data were abstracted on tubal ligations and pregnancies occurring
      before April 1996. RESULTS: A total of 63% of HIV-positive women used cocaine
      during the index pregnancy and 26% also used opiates. HIV-positive women had
      fewer tubal ligations than group 1 (38.9% versus 51.1%, P = 0.058), but there was
      no difference when matching included drug use (38.9% in group 2). HIV infection
      was associated with a decrease in the number of pregnancies; this decrease was
      most marked when matching included drug use (18.0 versus 32.1 pregnancies per 100
      woman-years,P < 0.01). There were no significant differences in spontaneous or
      therapeutic terminations. Poisson regression analysis demonstrated that HIV
      infection and older age were associated with fewer pregnancies, and cocaine use
      with an increased pregnancy rate. CONCLUSION: This study confirms that HIV
      infection is associated with a decrease in the number of pregnancies, but also
      illustrates the confounding effects of illicit drug use among women in the United
      States.

PMID- 11834961
TI  - Avascular necrosis of the bone in HIV-infected patients: incidence and associated
      factors.

PMID- 11834962
TI  - Immunological recovery after 3 years' antiretroviral therapy in HIV-1-infected
      children.

PMID- 11834963
TI  - Decrease in HIV-1 seminal shedding in men receiving highly active antiretroviral
      therapy: an 18 month longitudinal study (ANRS EP012).

PMID- 11834964
TI  - Primary HIV-1 drug resistance in Abidjan (Cote d'Ivoire): a genotypic and
      phenotypic study.

PMID- 11834965
TI  - HIV incidence and associated risk factors among young injection drug users.

PMID- 11834966
TI  - Virological characteristics of hepatitis C virus infection in HIV-infected
      individuals with chronic hepatitis C: implications for treatment.

PMID- 11834967
TI  - Acceptance by Belgian physicians of in-vitro fertilization treatment in women
      with HIV infection.

PMID- 11834968
TI  - Exclusive breast-feeding and HIV transmission.

PMID- 11834969
TI  - Modelling HIV incidence in gay men: increased treatment, unsafe sex and sexually
      transmissible infections.

PMID- 11834970
TI  - Cross-neutralizing antibodies against primary isolates in African women infected
      with HIV-1.

PMID- 11834971
TI  - Reduction of HIV-1 viral load in saliva by indinavir-containing antiretroviral
      regimen.

PMID- 11834972
TI  - Probable interaction between efavirenz and cyclosporine.

PMID- 11834974
TI  - Transmission of HIV-1 variants resistant to the three classes of antiretroviral
      agents: implications for HIV therapy in primary infection.

PMID- 11834973
TI  - Gynaecomastia without lipodystrophy in HIV-1-seropositive patients on efavirenz:
      an alternative hypothesis.

PMID- 11834975
TI  - Rhodococcus equi pneumonia: highly active antiretroviral therapy helps but does
      not cure lung infection.

PMID- 11834976
TI  - Fracture locations influence the likelihood of rectal and lower urinary tract
      injuries in patients sustaining pelvic fractures.
AB  - BACKGROUND: Rectal and lower urinary tract injuries in pelvic fractures can lead
      to significant complications. We sought to determine whether fracture locations
      could serve as markers for injury. METHODS: In our retrospective review of
      patients with blunt pelvic fractures, the association of fracture locations with
      injury to the rectum, bladder, and urethra was explored with Fisher's exact test
      and subsequently analyzed with multiple logistic regression. RESULTS: Of the 362
      patients reviewed, 8 had rectal injury and 24 had lower urinary tract injury. The
      following locations were found to be significant. Rectum: symphysis pubis
      (relative risk [RR] = 3.3, p < 0.001) and sacroiliac (SI) joint (RR = 2.1, p =
      0.014). Bladder: symphysis pubis (RR = 2.1, p < 0.001), SI joint (RR = 2.0, p <
      0.001), and sacrum (RR = 1.6, p = 0.002). Urethra: symphysis pubis (RR = 2.9, p =
      0.003), SI joint (RR = 1.8, p = 0.04), and inferior ramus (RR = 4.6, p = 0.008).
      After multivariate analysis, the primary and independent predictors for each of
      the injuries were as follows: rectal injury, widened symphysis; bladder injury,
      widened symphysis and SI joint; and urethral injury, widened symphysis and
      fracture of the inferior pubic ramus. Although these associations were
      significant, the overall prevalence of associated rectal and urologic injuries
      was low. Consequently, the predictive values of these radiologic findings were
      also low, ranging from 5% to 9% for urethral and rectal injuries to 20% for
      bladder injuries. CONCLUSION: Certain fracture locations are associated with
      increased risk for rectal, bladder, or urethral injury. Fractures involving these
      locations should prompt further work-up for assessment.

PMID- 11834977
TI  - A thoracostomy tube guideline improves management efficiency in trauma patients.
AB  - BACKGROUND: Thoracostomy tube (TT) placement constitutes primary treatment for
      traumatic hemopneumothorax. Practice patterns vary widely, and criteria for
      management and removal remain poorly defined. In this cohort study, we examined
      the impact of implementation of a practice guideline (PG) on improving management
      efficiency of thoracostomy tube. METHODS: We developed a PG aimed at
      standardizing the management of TTs in critically ill patients admitted to a
      Level I trauma center. During the 9-month period before (Pre-PG) and 3 months
      after (Post-PG) implementation, practice parameters including prophylactic
      antibiotics, duration of TT therapy, preremoval chest radiographs with associated
      charges, and complications were evaluated. Differences between groups were
      assessed by Mann-Whitney rank sum and chi(2) with Yates correction. RESULTS:
      There were 61 patients, 14 in the Pre-PG group and 47 in the Post-PG group. The
      groups were matched in age and Injury Severity Scores. The Post-PG cohort
      averaged 3 fewer days of TT therapy. After implementation of the PG, 21 patients
      did not have preremoval chest radiography, representing a $3000 reduction in
      radiology fees. Complication rates (retained pneumothorax, hemothorax, and
      empyema) were not different between the two groups. CONCLUSION: Implementation of
      a thoracostomy tube practice guideline was associated with improved management
      efficiency in trauma patients.

PMID- 11834978
TI  - Aggressive driving: a preliminary analysis of a serious threat to motorists in a
      large metropolitan area.
AB  - OBJECTIVE: Aggressive driving is consistently rated as the leading concern of
      motorists in our metropolitan area, ahead of even "drunken driving." Few
      objective data exist on the incidence of aggressive driving. The purpose of this
      study was to determine the incidence of selected aggressive driving behaviors and
      to establish a baseline for future interventions and research. METHODS: Speeding,
      traffic signal violations ("red-light running"), and stop-sign violations were
      studied. Speeding data were recorded by inductance loops embedded in major
      roadways (n = 10). Data were collected from red-light cameras (n = 73 cameras, 82
      sites) and by trained observers at intersections with traffic signals (n = 15) or
      stop signs (n = 15). Data included total traffic volume, numbers of violations,
      and each violator's speed. RESULTS: The majority of motorists on major roadways
      drive at speeds exceeding the speed limit and between 40% and 80% of vehicles
      were traveling at 10 mph or more over the speed limit. Red-light running occurred
      at equivalent rates both by camera (1.5 violations/1,000 vehicles) and by
      observer (1.3 violations/1,000 vehicles). The absolute numbers of red-light
      violations were extremely high (approximately 30,000 per month), and 16% violated
      the signal at > 10 mph above the speed limit. The incidence of "at-speed" (i.e.,
      without slowing) stop-sign violations was dramatic (17.5 violations/1,000
      vehicles). These were confirmed by video review and represent high risk for
      crashes. CONCLUSION: Aggressive driving behaviors are frequent and often include
      very dangerous actions. Currently available deterrents appear to have limited
      impact in our congested area. Inadequate resources for enforcement and limited
      public awareness may be partially responsible. We have adopted a
      multidisciplinary approach to this serious problem including public education,
      stepped-up enforcement, and psychological treatments.

PMID- 11834979
TI  - Motor vehicle restraints: primary versus secondary enforcement and ethnicity.
AB  - BACKGROUND: Efforts to increase motor vehicle restraint use have been broadly
      based rather than focused on specific populations. Identifying specific issues,
      including populations with low restraint use, can help target educational
      campaigns. Previous studies have reported differences in restraint use by
      ethnicity. This study was performed to determine whether differences exist in
      motor vehicle restraint use by ethnicity and whether these differences are
      altered by the presence of primary versus secondary restraint laws. METHODS: Data
      were collected on motor vehicle crash victims admitted to two Level I trauma
      centers from October 1, 1997, through March 31, 1998; one in a state with primary
      restraint enforcement (motorist can be stopped for the restraint violation), the
      other with a secondary restraint law (restraint violation may be enforced if the
      motorist is stopped for another violation). Data were obtained concurrently with
      hospitalization and entered into computerized trauma registry databases. RESULTS:
      Restraint use in all motor vehicle crash victims was significantly different
      between the primary and secondary enforcement states (58% vs. 37%, p < 0.001).
      Additionally, restraint use varied markedly by ethnicity in the secondary
      enforcement state (Caucasian, 42%; vs. African-American, 21%, and Hispanic, 26%,
      p < 0.02, chi(2)). Comparison of restraint use in primary versus secondary
      enforcement states demonstrated significantly increased restraint use in all
      ethnic groups (p < 0.01). CONCLUSION: In a state with secondary enforcement laws,
      restraint use varied significantly with ethnicity. Restraint use was markedly
      increased in all ethnic groups by the presence of a primary enforcement law.
      Implementation and enforcement of primary restraint laws is essential to
      improving motor vehicle restraint use. Educational campaigns to increase
      restraint use need to target specific populations.

PMID- 11834980
TI  - TRISS unexpected survivors: an outdated standard?
AB  - BACKGROUND: Performance improvement is an essential component of the trauma
      center. TRISS methodology has been applied as a national standard against which
      trauma centers can compare their outcomes. Earlier reviews of TRISS unexpected
      survivors sustained the classification of unexpected survivor in the vast
      majority of cases. Our hypothesis was that the level of care that is currently
      expected has made the TRISS unexpected survivors a statistical phenomenon only.
      METHODS: Two hundred seventy TRISS unexpected survivors at a Level I trauma
      center from 1991 to 1995 were reviewed. Each case was reviewed as a blinded
      abstract by six reviewers (three of whom are directors at other facilities) and
      classified as clinically unexpected survivor (confirmed TRISS classification) or
      clinically expected survivor (did not sustain TRISS classification as unexpected
      survivor). Data are expressed as mean +/- SD. Statistical significance was
      achieved at p < 0.05. RESULTS: Among the 270 patients categorized by TRISS as
      unexpected survivors, only 10.7% were corroborated as clinically unexpected
      survivors by this peer review process and 89.3% were reclassified as clinically
      expected survivors. Confirmed clinically unexpected survivors were more likely to
      go directly from the emergency department to the operating room (82 vs. 46%; p <
      0.05). Age (32 +/- 12 years vs. 40 +/- 19 years; p < 0.05), Injury Severity Score
      (46 +/- 20 vs. 32 +/- 14; p < 0.05), Revised Trauma Score (2.46 +/- 1.89 vs. 3.11
      +/- 1.21; p < 0.05), probability of survival (0.13 +/- 0.13 vs. 0.24 +/- 0.15; p
      < 0.05), systolic blood pressure in the emergency department (60 +/- 51 mm Hg vs.
      109 +/- 33 mm Hg; p < 0.05), hospital length of stay (39.6 +/- 30.3 days vs. 24.0
      +/- 23.0 days; p < 0.05), and intensive care unit length of stay (19.5 +/- 20.6
      days vs. 9.6 +/- 10.1 days; p < 0.05) were significantly different comparing
      confirmed versus unsustained classification as unexpected survivors. CONCLUSION:
      Only 10.7% of survivors classified as unexpected by TRISS were corroborated as
      unexpected by a blinded, peer-review process. TRISS needs to be updated for
      meaningful interpretation; modifications need to be made and coefficients need to
      be revised.

PMID- 11834981
TI  - A new method for estimating probability of survival in pediatric patients using
      revised TRISS methodology based on age-adjusted weights.
AB  - BACKGROUND: TRISS methodology estimates probability of survival (P(s)) based on
      coefficients derived largely from adult data. We developed a novel pediatric age
      specific method to estimate P(s). METHODS: The Pennsylvania Trauma Outcome Study
      database was queried for pediatric patients injured between 1993 and 1996 (n =
      9730). P(s) derived from the Pediatric Age-Adjusted TRISS (PAAT) methodology was
      generated using our Age-Specific Pediatric Trauma Score and Injury Severity Score
      with corresponding weights. A test data set of 7138 pediatric patients entered in
      the Pennsylvania Trauma Outcome Study from 1997 to 1999 was used to compute an
      expected number of survivors for PAAT, TRISS, and ASCOT (A Severity
      Characteristic of Trauma). Observed and expected survival were compared for blunt
      injured patients, for head injured patients, and by age category. RESULTS: PAAT
      showed no significant difference between observed and expected survival. TRISS
      and ASCOT significantly underestimated overall survival: across age groups, for
      blunt injuries, for head injuries, and for patients whose P(s) was less than 91%.
      CONCLUSION: PAAT offers a more reliable methodology than TRISS and ASCOT for
      comparing pediatric trauma outcomes.

PMID- 11834982
TI  - When is an elder old? Effect of preexisting conditions on mortality in geriatric
      trauma.
AB  - BACKGROUND: As the U.S. population ages, the number of geriatric trauma victims
      will continue to grow. Outcomes are known to be worse for these patients, in
      large part because of preexisting conditions (PECs). The specific impact of
      various PECs on outcome in geriatric trauma has not been well studied because of
      heterogeneous data sets and sample sizes. METHODS: We sought to define the impact
      of clinical variables and PECs on mortality in geriatric trauma by analyzing a
      large statewide trauma database. We defined geriatric trauma patients as those
      age > or = 65. Isolated hip fractures were excluded. We used multiple logistic
      regression to determine the effect of 21 different PECs on 30-day in-hospital
      mortality. RESULTS: Data were abstracted from 33,781 patient records. Overall
      mortality was 7.6%. For each 1-year increase in age beyond age 65, odds of dying
      after geriatric trauma increased by 6.8% (95% confidence interval, 6.1-7.5%).
      When presenting vital signs, Glasgow Coma Scale score, and ISS were controlled,
      PECs with the strongest effect on mortality were hepatic disease (odds ratio
      [OR], 5.1), renal disease (OR, 3.1), and cancer (OR, 1.8). Chronic steroid use
      increased the odds of death after geriatric trauma (OR, 1.6), whereas Coumadin
      therapy did not. CONCLUSION: Considered independently, these data are
      insufficient to allow withdrawal of care, but this information may be a useful
      component to help in guiding families faced with difficult decisions after
      geriatric trauma.

PMID- 11834983
TI  - Confirmation of the safety and accuracy of physical examination in the evaluation
      of knee dislocation for injury of the popliteal artery: a prospective study.
AB  - BACKGROUND: Knee dislocation, which poses a significant risk for injury of the
      popliteal artery, prompts many surgeons to evaluate these patients with
      arteriography routinely. Our hypothesis was that physical examination alone
      (without arteriography) accurately confirms or excludes surgically significant
      vascular injuries associated with knee dislocation. METHODS: All patients
      diagnosed with a knee dislocation by an attending orthopedic surgeon between
      January 1990 and January 2000 were prospectively managed by protocol at our Level
      I trauma center according to their physical examination. Those with hard signs
      (active hemorrhage, expanding hematoma, absent pulse, distal ischemia,
      bruit/thrill) underwent arteriography followed immediately by surgical repair if
      indicated. Patients with no hard signs (negative physical examination) were
      admitted for 23 hours, underwent serial physical examination, and then followed
      as outpatients. RESULTS: There were 35 knee dislocations in 35 patients during
      this 10-year period. The average age was 31 years; 18 dislocations were on the
      right knee and 17 were on the left. Two patients died from closed head injuries
      and multisystem trauma. Eight patients were found to have hard signs (positive
      physical examination) either at presentation (six patients) or during their
      hospitalization after reduction of their dislocation (two patients). All eight
      patients demonstrated a loss of pulses only. Six of these patients showed
      occlusion of the popliteal artery on arteriography and underwent surgical repair
      without complication (five vein grafts, one primary repair), one demonstrated
      spasm of the popliteal artery, and one showed a normal artery that required no
      treatment. None of the 27 patients with negative physical examination during
      their hospitalization ever developed limb ischemia, needed an operation for
      vascular injury, or experienced limb loss. Sixteen patients were available for
      follow-up (46%). Twelve patients with negative physical examination (44%) were
      contacted (mean, 13 months; range, 2-35 months), and four of the eight patients
      with positive physical examination (50%) and surgical repair were contacted
      (mean, 19 months; range, 6-49 months). None of the patients in either group
      developed any vascular-related symptoms or suffered from a vascular repair
      complication over the follow-up interval. CONCLUSION: This limited series
      suggests that the presence or absence of an injury of the popliteal artery after
      knee dislocation can be safely and reliably predicted, with a 94.3% positive
      predictive value and 100% negative predictive value. Arteriography appears to be
      unnecessary when physical examination is negative but may avert negative vascular
      exploration when physical examination is positive. This approach substantially
      reduces cost and resource use without adverse impact on the patient.

PMID- 11834984
TI  - Continuous fluid resuscitation and splenectomy for treatment of uncontrolled
      hemorrhagic shock after massive splenic injury.
AB  - BACKGROUND: Using a standardized massive splenic injury (MSI) model of
      uncontrolled hemorrhagic shock, we studied the effect of continuous fluid
      resuscitation and splenectomy on the hemodynamic response and survival in rats.
      METHODS: The animals were randomized into seven groups: group 1 (n = 8), sham
      operated; group 2 (n = 8), MSI untreated; group 3 (n = 8), MSI treated with 7.5
      mL/kg/h of 7.5% NaCl (hypertonic saline [HTS]) for 1 hour; group 4 (n = 8), MSI
      treated with 7.5 mL/kg/h hydroxyethyl starch (HES-7.5) for 1 hour; group 5 (n =
      8) MSI treated with 35 mL/kg/h Ringer's lactate (RL) solution (RL-35) for 1 hour;
      group 6 (n = 8) MSI treated with 70 mL/kg/h RL for 1 hour (RL-70); and group 7 (n
      = 8), MSI treated with 105 mL/kg/h RL for 1 hour (RL-105). In all MSI groups,
      splenectomy was performed 45 minutes after injury. RESULTS: MSI in untreated
      group 2 resulted in a fall of mean arterial pressure from 105.9 +/- 10.7 mm Hg to
      27.0 +/- 6.7 mm Hg (p < 0.001) in 60 minutes. Mean survival time after
      splenectomy in this group was 160.7 +/- 29.7 minutes, and total blood loss was
      34.8 +/- 4.7% of blood volume. Continuous HTS infusion with splenectomy in group
      3 was followed by a total blood loss of 38.7 +/- 4.4% and mean survival time was
      176.5 +/- 23.2 minutes. HES-7.5 infusion and splenectomy was followed by a total
      blood loss of 39.6 +/- 2.5% and survival time was 171.6 +/- 19.5 minutes.
      Continuous infusion of increasing volumes of RL in groups 5, 6, and 7 was
      followed by increase in blood loss to 29.0 +/- 4.1%, 50.2 +/- 3.1% (p < 0.001),
      and 62.7 +/- 7.1% (p < 0.002) of total blood volume, respectively. Mean survival
      time in groups 5, 6, and 7 was 233.5 +/- 6.5 minutes (p < 0.04), 207.6 +/- 17.0
      minutes (p < 0.05), and 158 +/- 26 minutes, respectively. CONCLUSION: Continuous
      infusion of large-volume RL and splenectomy after massive splenic injury resulted
      in a significant increase in intra-abdominal bleeding and shortened survival time
      compared with small-volume RL infusion.

PMID- 11834985
TI  - Postinjury malaria: a study of trauma victims in cambodia.
AB  - BACKGROUND: The pattern of host defense against plasmodium is comparable to the
      immune response to bacterial infection. Posttraumatic immunosuppression may
      therefore cause relapses of malaria secondary to trauma and trauma surgery in
      asymptomatic carriers of the parasites in endemic areas. To our knowledge this
      has not been validated in epidemiologic studies. METHODS: Postinjury malaria was
      registered retrospectively in 342 land mine and war victims from malaria-endemic
      areas in Cambodia. The incidence rate was analyzed in terms of age, gender,
      preinjury endemicity, evacuation times, anatomic injury severity, systolic blood
      pressure at admission, blood transfusion, and duration of the first surgical
      intervention as independent variables. RESULTS: The rate of postinjury malaria in
      the study patients was 33.3% (95% CI, 28.3-38.3%). Injury Severity Score (ISS)
      and surgical operation time were risk factors (area under the curve in receiver
      operating characteristic plots were 0.73 and 0.79, respectively). The impact of
      the other risk factors was nonsignificant. CONCLUSION: Despite difficulties in
      diagnosing postoperative malaria in endemic areas, the study demonstrates that
      the rate of postinjury malaria is high. The results legitimate controlled trials
      of immediate postinjury chemoprophylaxis to severely injured in endemic areas.
      The authors recommend staged surgical operations with brief primary interventions
      in victims with severe injuries.

PMID- 11834986
TI  - Firearm availability and unintentional firearm deaths, suicide, and homicide
      among 5-14 year olds.
AB  - BACKGROUND: In the United States, only motor vehicle crashes and cancer claim
      more lives among children than do firearms. This national study attempts to
      determine whether firearm prevalence is related to rates of unintentional firearm
      deaths, suicides, and homicides among children. METHODS: Pooled cross-sectional
      time-series data (1988-1997) were used to estimate the association between the
      rate of violent death among 5-14 year olds and four proxies of firearm
      availability, across states and regions. RESULTS: A statistically significant
      association exists between gun availability and the rates of unintentional
      firearm deaths, homicides, and suicides. The elevated rates of suicide and
      homicide among children living in states with more guns is not entirely explained
      by a state's poverty, education, or urbanization and is driven by lethal firearm
      violence, not by lethal non-firearm violence. CONCLUSION: A disproportionately
      high number of 5-14 year olds died from suicide, homicide, and unintentional
      firearm deaths in states and regions where guns were more prevalent.

PMID- 11834987
TI  - All patients with truncal gunshot wounds deserve trauma team activation.
AB  - BACKGROUND: Traditional criteria for trauma team activation (TTA) include
      hypotension, tachycardia, tachypnea, and unresponsiveness. In a recent revision
      of the Resources for Optimal Care of the Trauma Patient, gunshot wound to the
      trunk (GSWT) was recommended as an independent criterion for major resuscitation
      and TTA. To validate this suggestion, we reviewed records of patients with GSWT
      to see if patients not meeting standard TTA criteria had serious injuries that
      would benefit from TTA. METHODS: This study was a retrospective trauma registry
      study at a large Level I trauma center. Records of all patients over an 8.5-year
      period with GSW to chest, back, or abdomen/pelvis were included in the study.
      Patients who died in hospital, required ICU admission within 24 hours, had non
      orthopedic operation within 24 hours, or had ISS > 15 were considered severely
      injured, and were assumed to benefit from TTA. RESULTS: Between January 1993 and
      June 2000, 4,198 patients were admitted with GSWT, 94% of whom met traditional
      TTA criteria. Sixty-one percent of patients meeting traditional TTA criteria had
      severe injury, compared with 45.7% for those without TTA criteria. Of the 234
      patients who did not meet traditional TTA criteria, 9.4% required early ICU
      admission, 29.5% required non-orthopedic operation within 24 hours, and 1.3%
      died. CONCLUSION: Patients with GSWT often require high-level care, even when
      physiologic TTA criteria are absent on admission. Gunshot wound to the trunk
      should be an independent criterion for TTA.

PMID- 11834988
TI  - Transthoracic echocardiography is not cost-effective in critically ill surgical
      patients.
AB  - BACKGROUND: Echocardiography has been shown to be valuable in critically ill
      surgical patients. Transthoracic echocardiography (TTE) often fails to provide
      adequate imaging in critically ill patients, necessitating subsequent
      transesophageal echocardiography (TEE). The objective of this study was to
      determine and quantify factors associated with failure of transthoracic
      echocardiography (TTE) in critically ill surgical patients, and to define a cost
      effective strategy for echocardiography in these patients. METHODS: Demographic
      and clinical data were collected retrospectively and evaluated to determine which
      factors were associated with failure of TTE to provide adequate imaging. In
      addition, models were developed to estimate costs for echocardiography in
      critically ill surgical patients. RESULTS: TTE has a high failure rate in
      critically ill surgical patients. This failure rate increases significantly in
      patients who gain > 10% body weight from admission weight, who are supported with
      > or = 15 cm H(2)O positive end-expiratory pressure, and in those with chest
      tubes. As a result, the use of TTE in critically ill surgical patients is not
      cost-effective. TEE, however, is highly effective in this group of patients, and
      is more cost-effective than TTE in evaluating those critically ill surgical
      patients requiring echocardiography. CONCLUSION: The routine use of TTE to
      initially evaluate all critically ill surgical patients who require
      echocardiography should be abandoned because it is not cost-effective. TEE
      appears to be the most cost-effective echocardiographic modality in the surgical
      intensive care unit.

PMID- 11834990
TI  - Effect of medium tonicity and dextran on neutrophil function in vitro.
AB  - BACKGROUND: Multiple investigations have demonstrated that hypertonic saline (HS)
      diminishes the response of polymorphonuclear leukocytes (PMNs) to stimulation.
      Recent meta-analysis suggests that hypertonic saline in dextran (HSD) is
      clinically superior to HS. No work to date has examined the effect of added
      dextran on this immunomodulatory property. METHODS: Human PMNs were exposed to
      media of varying osmolarity (220-360 mOsm/L) and stimulated with f-met-leu-phe
      with or without dextran present in the medium. Cell volume, respiratory burst,
      PMN aggregation, and beta(2)-integrin (CD18) expression were measured. RESULTS:
      Stimulation with f-met-leu-phe increased cell volume, respiratory burst,
      aggregation, and CD18 expression. The increases in cell volume, respiratory
      burst, and aggregation were significantly attenuated by exposure to hypertonic
      medium. The addition of dextran to the media did not change the results.
      CONCLUSION: The alterations in PMN function associated with HS are not changed or
      attenuated by the addition of dextran, suggesting that the clinically superior
      HSD may have effects similar to HS in mitigating the tissue damage associated
      with activated PMNs.

PMID- 11834991
TI  - The Gotfried PerCutaneous Compression Plate versus the Dynamic Hip Screw in the
      treatment of pertrochanteric hip fractures: minimal invasive treatment reduces
      operative time and postoperative pain.
AB  - BACKGROUND: The PerCutaneous Compression Plate (PCCP) was developed by Gotfried
      (Israel, Haifa) for minimal-approach osteosynthesis of pertrochanteric fractures.
      METHODS: One hundred fifteen patients, aged 60 or more, with intertrochanteric
      fractures (AO type 31A1 or 31A2) were selected randomly for fixation with either
      the PCCP (53 patients) or the Dynamic Hip Screw (62 patients). All surviving
      patients were scheduled for a 1-year follow-up. RESULTS: Less invasive surgical
      stabilization of pertrochanteric fractures with the PCCP resulted in shorter
      theater and surgical time and reduced postoperative pain. The PCCP treatment
      showed a tendency toward a lower transfusion need and a reduction of fracture
      impaction; however, results were not statistically significant. There was a trend
      toward a higher mechanical complication rate with the PCCP: anatomic closed
      reduction without posterior sagging of the fracture and fluoroscopic control of
      the placement of the first neck screw in two directions are essential to avoid
      technical complications. CONCLUSION: Minimal invasive treatment of
      pertrochanteric fractures with the PCCP reduces operation time and postoperative
      pain.

PMID- 11834992
TI  - Timing of femur fracture fixation: effect on outcome in patients with thoracic
      and head injuries.
AB  - BACKGROUND: Optimal timing of femur fracture fixation remains controversial. This
      study examines the association between the timing of femur fracture fixation and
      outcome in patients with concomitant chest and head injuries. METHODS: A
      retrospective review of registry data from a Level I trauma center identified
      1362 patients with a femoral shaft fracture over a 12-year period. Patients were
      categorized into five groups by timing of femur fracture fixation: Group 1,
      within 24 hours; Group 2, 24 to 48 hours; Group 3, 48 to 120 hours; Group 4, >
      120 hours; and Group 5, patients with no operative fixation. Primary outcome
      measures included morbidity (specifically, pulmonary complications) and
      mortality. Secondary outcome measures were hospital length of stay, intensive
      care unit length of stay, and discharge Glasgow Coma Scale score. Subsets of
      patients were examined including all patients with multiple injuries (Injury
      Severity Score > 15), chest trauma (Chest Abbreviated Injury Scale score > or =
      2), and head trauma (Head Abbreviated Injury Scale score > or = 2). RESULTS:
      Acute respiratory distress syndrome, pneumonia, hospital length of stay, and
      intensive care unit length of stay were lowest in the group fixed within 24
      hours, even in patients with concomitant head or chest trauma. Fixation between 2
      and 5 days was associated with a significantly increased incidence of acute
      respiratory distress syndrome, pneumonia, and fat embolization syndrome in
      patients with concurrent chest trauma (p < 0.0001). In head-injured patients,
      discharge Glasgow Coma Scale score was highest in the group fixed within 24
      hours. Timing of operative fixation did not affect mortality. CONCLUSION: Our
      data show that early femur fracture fixation (< 24 hours) is associated with an
      improved outcome, even in patients with coexistent head and/or chest trauma.
      Fixation of femur fractures at 2 to 5 days was associated with a significant
      increase in pulmonary complications, particularly with concomitant head or chest
      trauma, and length of stay. Chest and head trauma are not contraindications to
      early fixation with reamed intramedullary nailing.

PMID- 11834994
TI  - Similar central hemodynamics and oxygenation in reamed and unreamed
      intramedullary nailing of tibial fractures.
AB  - BACKGROUND: Reamed intramedullary nailing of a long bone fracture is considered
      to be of crucial importance in the genesis of pulmonary disturbances. Use of
      unreamed nailing technique has been encouraged to avoid temporary deterioration
      in lung functions. METHODS: Central hemodynamic changes were recorded in 20
      healthy adults with a unilateral simple tibial fracture undergoing reamed or
      unreamed intramedullary nailing. The patients were cannulated with a pulmonary
      artery catheter. Intramedullary nailing was performed during general anesthesia.
      Pre- and immediate postoperative hemodynamic variables were compared. RESULTS:
      Unchanged cardiac performance but pathologically altered pulmonary vascular tone
      were unrelated to the type of nailing technique. Increased oxygen consumption was
      observed as well. CONCLUSION: Changes in cardiac and pulmonary hemodynamics are
      already present after the trauma and before the intramedullary nailing procedure.

PMID- 11834995
TI  - The pathomechanism of posttraumatic edema of lower limbs: I. The effect of
      extravasated blood, bone marrow cells, and bacterial colonization on tissues,
      lymphatics, and lymph nodes.
AB  - BACKGROUND: The mechanical injury of soft tissues and bones of lower extremities
      is frequently followed by long-lasting edema at the site of trauma and distally.
      The pathomechanism of this complication remains unclear. Venous thrombosis and
      interruption of lymphatics are considered to be the main etiologic factors. We
      propose a concept that protracted healing of injured tissues and bones with
      involvement of the regional lymphatic system (lymphatics and nodes) is
      responsible for persistence of edema. The events affecting the first (scavenging)
      phase of healing of traumatized tissues, such as hematoma, translocation of bone
      marrow cells to soft tissues, and colonization by microorganisms, and in
      particular their effects on lymphatics and lymph nodes, were studied. METHODS:
      Mongrel dogs weighing 15-20 kg were used. Fresh blood or bone marrow cell (BMC)
      suspension was injected subcutaneously or intralymphatically into the paw.
      Strains of saprophyte bacteria residing on the skin surface were cultured and
      injected intradermally. Oil-contrast lymphography was performed before and after
      injections to evaluate the changes in lymphatics and nodes. Biopsy samples of paw
      skin, subcutaneous tissue, and regional lymph nodes (LN) were taken. The
      responsiveness of LN lymphocytes was studied in autologous mixed cultures with
      peripheral blood lymphocytes (PBL), BMC, and cultured bacteria. RESULTS: The PBL
      from subcutaneously injected blood were evacuated by the lymphatic route at a
      rate of 1-3%/6 hr. There was no thrombosis of lymphatic vessels or obstruction of
      LN sinusoids. The BMC evoked major inflammatory changes in both the skin and the
      LN. Bacteria caused local inflammation, dilatation of lymphatics, and destruction
      of node parenchyma. Autologous BMC and PBL stimulated LN lymphocytes in a 6-day
      culture. The responsiveness of lymph node lymphocytes to previously
      subcutaneously injected bacterial antigens was increased. CONCLUSION: The
      extravasated blood did not produce changes in skin, subcutaneous tissue, and
      lymphatics; however, it stimulated LN lymphocytes. The BMC and saprophyte
      bacteria caused major local and lymph node inflammatory response. All these
      factors may contribute to the local edema in the initial phases of healing of
      traumatized tissues.

PMID- 11834996
TI  - Immediate spinal cord decompression for cervical spinal cord injury: feasibility
      and outcome.
AB  - BACKGROUND: The effect of immediate surgical spinal cord decompression on
      neurologic outcome after spinal cord injury is controversial. Experimental models
      strongly suggest a beneficial effect of early decompression but there is little
      supportive clinical evidence. This study is designed to evaluate the feasibility
      and outcome of an immediate spinal cord decompression treatment protocol for
      cervical spinal cord injury in a tertiary treatment center. METHODS: To address
      this issue, 91 consecutive patients with acute, traumatic cervical spinal cord
      injury (1990-1997) were prospectively studied. Sixty-six patients (protocol
      group) underwent emergency magnetic resonance imaging (MRI) to determine the
      presence of persistent spinal cord compression followed, if indicated, by
      immediate operative decompression and stabilization. Twenty-five patients were
      managed outside the treatment protocol because of contraindication to magnetic
      resonance imaging, need for other emergency surgical procedures, or admitting
      surgeon preference (reference group). The protocol and reference groups had
      similar sex and age distributions, admitting Frankel grades, levels of neurologic
      injury, and Injury Severity Scores. RESULTS: Twenty-seven percent of patients
      seen were not enrolled in the treatment protocol because of the need for other
      emergent surgical treatment, contraindication to MRI, and specific surgeon bias
      regarding the "futility" of emergent treatment. The neurologic outcome for the
      patients in the reference group were similar to that in the previously reported
      literature. Fifty percent of protocol patients, compared with only 24% of
      reference patients, improved from their admitting Frankel grade. Eight protocol
      patients (12%), but no reference patients, improved from complete motor
      quadriplegia (Frankel grade A or B) to independent ambulation (Frankel grade D or
      E). Protocol patients required shorter intensive care unit stays, and shorter
      total hospital stays than reference patients. In the treatment protocol group,
      spinal cord decompression, confirmed by MRI, was achieved with immediate spinal
      column alignment and skeletal traction in 32 patients (46%). Thirty-four patients
      (54%) required emergent operative spinal cord decompression because of MRI
      documented persistent spinal cord compression. CONCLUSION: We conclude that
      immediate spinal column stabilization and spinal cord decompression, based on
      magnetic resonance imaging, may significantly improve neurologic outcome. The
      feasibility of such a treatment protocol in a tertiary treatment center is well
      demonstrated. Additional multicenter trials are necessary to achieve definitive
      conclusions regarding clinical efficacy.

PMID- 11834997
TI  - The effect of hyperbaric oxygen therapy on spinal fusion: using the model of
      posterolateral intertransverse fusion in rabbits.
AB  - BACKGROUND: The purpose of this study is to evaluate the facilitating effect of
      hyperbaric oxygen (HBO) on posterolateral intertransverse fusion using a
      validated rabbit model. METHODS: Twenty-four male New Zealand rabbits underwent
      posterolateral intertransverse fusion at L5-L6 with autogenous iliac bone graft.
      They were evenly divided into two groups: the HBO group and the normal room air
      (RA) group. Each group had six rabbits killed at 4 weeks and 8 weeks,
      respectively. The rabbits in the HBO groups were treated with 100% oxygen at 2.5
      atm for 2 hours a day. After being killed, all rabbits were subjected to
      radiographic examination, manual testing, and torsional loading to evaluate the
      results of spinal fusion. RESULT: Radiographic union of intertransverse fusion
      areas at 4-week RA, 4-week HBO, 8-week RA, and 8-week HBO were 2 of 12, 7 of 12,
      7 of 12, and 10 of 12, respectively. Solid union proven by manual palpation was
      found to be zero of six, three of six, four of six, and five of six of the cases,
      respectively. The average peak torsional momentums were 2120.2, 2576.5, 2661.6,
      and 3079.8 N-mm, respectively. Spinal fusion was significantly improved in the
      HBO groups at both 4 weeks and 8 weeks. CONCLUSION: The results of this study
      suggest that intermittent hyperbaric oxygen therapy will hasten the bone healing
      process and improve the fusion rate as compared with the non-HBO group.

PMID- 11834998
TI  - Early IL-6 plasma concentrations correlate with severity of brain injury and
      pneumonia in brain-injured patients.
AB  - BACKGROUND: Brain injury as well as early inflammatory and endocrine responses
      were found to be indicators for infectious complications in patients with
      multiple injuries. In this context, brain-derived inflammatory response as well
      as centrally triggered neuroendocrine activation and systemic immunodepression
      seem to be of major importance. Therefore, we hypothesize that a circulating
      index of inflammatory or endocrine function measured soon after brain injury (in
      patients with admission Glasgow Coma Scale [GCS] score of 4-7) would discriminate
      severe from moderate injury as indexed by GCS status on postinjury day 7.
      METHODS: In a retrospective study, 25 patients with either acute traumatic brain
      injury or cerebral hemorrhage and an initial GCS score of 4 to 7 were examined.
      Blood samples were obtained at different time points, and different immune
      variables and neuroendocrine hormones were determined. According to the GCS score
      on day 7, patients were divided into two groups (GCS score > or = 8, moderate
      brain injury; and GCS score < 8, severe brain injury or patients who died within
      the first week) for comparison of variables. Concluding from the results of this
      retrospective analysis, in a prospective study patients (n = 26) were divided
      into two groups according to their interleukin (IL)-6 plasma concentrations on
      day 1 (IL-6 > or = 100 pg/mL and IL 6 < 100 pg/mL). After 7 days, the GCS score,
      the infection rate, and the mortality were compared between these two groups.
      RESULTS: In the retrospective study, we could show that severe brain injury (as
      assessed by GCS score and mortality on day 7) was associated with high plasma
      levels of pro- and anti-inflammatory cytokines, acute phase proteins, and
      neuroendocrine hormones within 2 to 6 hours after the acute event. Among the
      investigated variables, elevated IL-6 plasma concentrations were stable up to 1
      day after the acute event with a high predictive value with regard to the short
      term prognosis and incidence of infectious complications within the first week.
      Because of this stability during the first 24 hours, we selected IL-6 for further
      studies. In the prospective study with a calculated cut-off IL-6 plasma
      concentration of 100 pg/mL on day 1, the predictive value of this parameter
      regarding the severity of the brain injury was fully confirmed (positive
      predictive value, 0.94; this value represents the observed pretest probability of
      0.62). All patients who died (n = 5) or developed infectious complications within
      the first week (n = 8) showed plasma IL-6 levels > or = 100 pg/mL on day 1.
      CONCLUSION: The IL-6 plasma level 1 day after the acute event with a cut-off of
      100 pg/mL (Immulite) seems to be a predictor for short-term prognosis and
      infectious complications in brain-injured patients.

PMID- 11834999
TI  - Vitamin D depletion following burn injury in children: a possible factor in post
      burn osteopenia.
AB  - BACKGROUND: Children burned > 40% total body surface area (TBSA) have chronically
      low bone mineral density (BMD) and increased risk for fractures and adult-onset
      osteoporosis. Because they are advised to avoid sunlight to prevent burn scar
      hyperpigmentation, we hypothesized that they develop vitamin D depletion, which
      could contribute to post-burn osteopenia. METHODS: We studied 24 children, ages 5
      20 years, burned > or = 40% TBSA 7.1 +/- 3.8 (SD) years, range 1.9-13.3 years,
      previously (n = 12) and 2.0 +/- 0.2, range 1.4-2.1 years, previously (n = 12), of
      which half received recombinant human growth hormone during the first post-burn
      year. We measured lumbar spine BMD, serum 25-hydroxyvitamin D (25(OH)D), 1,25
      dihydroxyvitamin D (1,25(OH)2D), intact PTH (iPTH), and osteocalcin. RESULTS:
      Serum 25(OH)D was low in 10/11 patients and 1,25(OH)2D was low in 5/11 at 7 years
      post-burn. Serum 25(OH)D was low in 10/12, while 1,25(OH)2D was low in 0/12 at 2
      years; osteocalcin was low in 9/12 in the 7-year group; iPTH levels were in the
      lowest quartile in 5/12 patients at 7 years and 10/12 patients at 2 years. Serum
      25(OH)D levels correlated with BMD z-scores, r = 0.53, p < 0.05, and inversely
      with iPTH levels, r = -0.66, p < 0.05, in the 7-year group. CONCLUSION: Burned
      children have low circulating levels of 25(OH)D which correlated with BMD z
      scores, suggesting that post-burn vitamin D depletion may play a role in the
      chronically low bone density observed in these children.

PMID- 11835000
TI  - Effects of burns on inhalation injury in sheep: a 5-day study.
AB  - BACKGROUND: We have previously reported that infliction of thermal injury
      immediately after smoke exposure did not accentuate pulmonary dysfunction during
      the subsequent 48 h. The purpose of this study was to determine whether thermal
      injury would aggravate pulmonary dysfunction during a longer postinjury period of
      5 days. METHODS: Six sheep (G1) received 12 units of smoke inhalation injury
      (SII) alone; seven sheep (G2) received a 40% full-thickness scald burn
      immediately after SII. All sheep were resuscitated with lactated Ringer's
      solution for the first 48 h. After 48 h, animals were fed food and water ad
      libitum. Cardiopulmonary variables and blood gases were measured serially. At the
      end of the 5-day experimental period, VA/Q distribution was analyzed using the
      multiple inert gas elimination technique (MIGET). Lung wet to dry (W/D) weight
      ratios and malondialdehyde (MDA) concentrations were determined. RESULTS: Cardiac
      index in G2 significantly increased and remained higher compared with G1. There
      was no difference in A-aDO(2) between the two groups. There was also no
      difference between the two groups by MIGET study, or in terms of lung MDA and W/D
      weight ratios. None of the animals manifested symptoms of infection. CONCLUSION:
      Despite the difference in the hemodynamic changes induced by the addition of a
      40% burn to smoke inhalation injury, pulmonary dysfunction was not accentuated
      during the 5-day study period in the absence of infection.

PMID- 11835002
TI  - Knee arthrodesis and limb lengthening in the treatment of infected total knee
      arthroplasty: case report.

PMID- 11835003
TI  - Use of antibiotic-impregnated bone cement nail to treat septic nonunion after
      open tibial fracture.

PMID- 11835004
TI  - Primary hyperparathyroidism and simultaneous bilateral fracture of the femoral
      neck during pregnancy.

PMID- 11835005
TI  - Neurologic injury caused by fracture of the iliac wing (Duverney's fracture):
      case report.

PMID- 11835006
TI  - Aortic and mitral valve disruption following nonpenetrating chest trauma.

PMID- 11835007
TI  - Stanford type a aortic dissection after blunt chest trauma: case report with a
      reflection on the mechanism of injury.

PMID- 11835008
TI  - Two-year follow-up after multiple injuries treated with endovascular stent
      grafting of aorta and transcatheter arterial embolization of spleen: minimal
      invasive surgery for an elderly patient.

PMID- 11835009
TI  - Endovascular management of acute traumatic thoracic aneurysm.

PMID- 11835011
TI  - Unusual thoracic outlet syndrome secondary to fractured clavicle.

PMID- 11835010
TI  - Thoracoscopic resection of painful multiple rib fractures: case report.

PMID- 11835012
TI  - Successful use of recombinant activated factor VII for trauma-associated
      hemorrhage in a patient without preexisting coagulopathy.

PMID- 11835014
TI  - Diaphragmatic rupture after a high speed car crash.

PMID- 11835013
TI  - Delayed presentations of aortic valve endocarditis in patients with thermal
      injury.

PMID- 11835015
TI  - Rupture of the right hemidiaphragm with liver herniation.

PMID- 11835016
TI  - Uncontrolled resuscitation and "sepsis".

PMID- 11835017
TI  - Publication policy, informed consent, and the randomized clinical trial.

PMID- 11835018
TI  - Improved efficacy and less bleeding: further evidence of a unique uncoupling of
      benefit and risk with bivalirudin.

PMID- 11835019
TI  - Stored iron and myocardial perfusion deficits.

PMID- 11835020
TI  - Adhesion molecules, platelet activation, and cardiovascular risk.

PMID- 11835021
TI  - The Low Energy Safety Study (LESS): rationale, design, patient characteristics,
      and device utilization.
AB  - BACKGROUND: A 10-J energy safety margin has traditionally been used in
      programming implantable cardioverter defibrillators (ICDs). The Low Energy Safety
      Study (LESS) tests the hypothesis that programming shocks to lower energy margins
      is safe and effective. METHODS: Patients with standard ICD indications undergo
      defibrillation threshold testing (DFT) at the time of ICD implant, with
      reconfirmation of lowest successful energy twice (DFT++). Patients are randomized
      to 2 groups: the first has the initial 2 shocks for ventricular fibrillation
      conversion programmed at 2 energy steps above DFT++ (typically 4-6 J, maximum 10
      J) with subsequent shocks at maximum energy, and the second has all shocks
      programmed at maximum energy. Patients are followed up every 3 months for 2 years
      to assess shock conversion efficacy of spontaneous arrhythmias. In a subgroup of
      patients, there is a second randomization to energy levels of 0, 1, 2, 3, or 4
      steps above implant DFT++ for conversion testing of 3 induced ventricular
      fibrillation episodes at prehospital discharge, 3 months, and 12 months after
      implant. RESULTS: Enrollment is complete (702 patients), but follow-up results
      are pending. There were no significant variations in implant indications and
      baseline antiarrhythmic drug use over the 3-year enrollment period, although an
      increase in the percentage of dual-chamber ICDs implanted occurred, with the
      majority (65%) of implanted ICDs being dual-chamber devices by the end of the
      enrollment period. CONCLUSION: The results of LESS should facilitate the
      development of algorithms for programming ICD energy safety margins.

PMID- 11835022
TI  - Persistence of the prothrombotic state after acute coronary syndromes:
      implications for treatment.
AB  - BACKGROUND AND RESULTS: Acute coronary syndromes (unstable angina and acute
      myocardial infarction) are generally caused by thrombosis over a disrupted
      atherosclerotic plaque. During the acute phase, antithrombotic therapy (including
      aspirin and heparin) has been shown to reduce the risk of death or myocardial
      infarction (MI). The purpose of this review is to examine the high-risk period
      for clinical thrombotic events that extends for several weeks after presentation
      and to review the treatments aimed at reducing these events. RESULTS: More than
      half of clinical events reported during the first month occur after the first 3
      to 5 days that comprise the standard in-hospital treatment period. Several
      different antithrombotic approaches have been tested, including longer duration
      of antiplatelet therapy, anticoagulant treatment, and oral glycoprotein (GP)
      IIb/IIIa inhibitors. Aspirin is effective at reducing risk, and clopidogrel
      provides additional benefit, as does dalteparin for at least the first month.
      Warfarin in addition to aspirin, while generally disappointing, has not been
      adequately tested at higher doses. Oral GP IIb/IIIa inhibitors cause a paradoxic
      increased risk of death for unclear reasons. CONCLUSION: Further reduction of
      risk during the weeks after presentation with acute coronary syndromes remains an
      important therapeutic goal.

PMID- 11835023
TI  - Highlights from the American Heart Association annual scientific sessions 2001:
      November 11 to 14, 2001.

PMID- 11835024
TI  - Bivalirudin as a replacement for unfractionated heparin in unstable angina/non-ST
      elevation myocardial infarction: observations from the TIMI 8 trial. The
      Thrombolysis in Myocardial Infarction.
AB  - BACKGROUND: The Thrombolysis in Myocardial Infarction (TIMI) 8 trial was
      undertaken to compare the efficacy and safety of bivalirudin versus
      unfractionated heparin in a double-blind phase III trial of patients with
      unstable angina/non-ST-elevation myocardial infarction (MI). METHODS: All
      patients received aspirin and were randomized either to unfractionated heparin
      (bolus of 70 U/kg followed by an infusion of 15 U/kg/h) or bivalirudin (bolus of
      0.1 mg/kg followed by an infusion of 0.25 mg/kg/h) for a minimum of 72 hours. The
      primary efficacy end point was a composite of all cause mortality or nonfatal
      recurrent MI. RESULTS: A total of 133 of the planned 5320 patients were enrolled,
      at which point the study was terminated by the sponsor because of a decision at
      the time to suspend further development of bivalirudin. Through 14 days, the
      incidence of death or nonfatal MI was 9.2% in the 65 patients in the
      unfractionated heparin group and was 2.9% in the 68 patients in the bivalirudin
      group, odds ratio (95% CI) 0.30 (0.06-1.53). Major hemorrhage occurred in 3
      patients in the unfractionated heparin group (4.6%) but in none of the patients
      in the bivalirudin group (P =.11). CONCLUSIONS: The trend toward a lower rate of
      death or nonfatal MI in the bivalirudin group is consistent with a therapeutic
      effect of the drug and is consistent with other trials of bivalirudin in patients
      with acute coronary syndromes. The potential for clinically meaningful
      antithrombotic activity without an increased risk of bleeding and availablility
      of an alternative anticoagulation strategy in patients who cannot tolerate
      unfractionated heparin are particularly attractive and underscore the need for
      further evaluation of bivalirudin.

PMID- 11835025
TI  - Elevated soluble P-selectin levels are associated with an increased risk of early
      adverse events in patients with presumed myocardial ischemia.
AB  - BACKGROUND: Cell adhesion molecules (CAMs) play a pivotal role in the
      interactions between leukocytes, platelets, and vascular endothelium. Soluble
      CAMs (sCAMs) are shed from cell surfaces and reflect cellular activation.
      Elevated levels of sCAMs have been reported in the acute coronary syndromes. We
      hypothesized, therefore, that sCAMs might prove of prognostic value in patients
      with acute chest pain presumed to be the result of myocardial ischemia. METHODS:
      One hundred twenty-six consecutive patients with chest pain, thought clinically
      to represent myocardial ischemia, were studied prospectively. Soluble
      intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1
      (sVCAM-1), E-selectin (sE-selectin) and P-selectin (sP-selectin) levels were
      assayed at presentation, as were cardiac troponin I (cTnI) and creatine kinase
      MB(mass) (CK-MB(mass)). The primary study end point was the occurrence of a
      serious cardiac event (SCE) during the index admission or the subsequent 3
      months. RESULTS: sP-selectin and cTnI levels were significantly higher among
      patients who had an early SCE (P =.006 and P <.001, respectively). Both remained
      independently predictive (P <.001) in a multivariate regression equation. The
      other independent predictor was a history of vascular disease (P <.05). No other
      markers were significant predictors of early outcome. CONCLUSION: Elevated sP
      selectin levels, but not those of other sCAMs, are predictors of early adverse
      events in patients with chest pain presumed caused by myocardial ischemia. Their
      utility in predicting the outcome of individual patients is, however, limited.

PMID- 11835026
TI  - Misreporting of myocardial infarction end points: results of adjudication by a
      central clinical events committee in the PARAGON-B trial. Second Platelet
      IIb/IIIa Antagonist for the Reduction of Acute Coronary Syndrome Events in a
      Global Organization Network Trial.
AB  - BACKGROUND: Myocardial (re)infarction (MI), a common trial end point, can be
      difficult to identify because of inconclusive signs and symptoms. We examined
      disagreement between investigator and clinical events committee (CEC) reporting
      of MIs in an international, randomized trial. METHODS: The primary end point of
      the PARAGON-B trial was a 30-day composite of death, MI (CEC adjudicated), or
      ischemia-driven intervention. If CEC and investigator determinations of MI
      differed, we sent investigators event summaries and rationales for CEC decisions
      and asked whether they now agreed with the CEC assessment. If they still
      disagreed, they were to provide a rationale and supporting data. Such cases were
      reviewed, and a final decision was made. RESULTS: Overall, 1736 of 5225 (33%)
      patients had suspected MIs; the CEC adjudicated 483 of 1736 (28%) as MIs. In 404
      patients (23%), investigator and CEC assessments of MI differed; 270 MIs were
      identified by the CEC but not investigators, and 134 were identified by
      investigators but not the CEC. Most disagreements concerned periprocedural MIs,
      but some reflected clinical ischemia and enzyme elevations. Letters for 382
      disagreements were sent and returned by investigators, and investigators came to
      agree with CEC assessments in 307 cases (80%). For the other 75 cases (20%),
      after review the investigators' assessments were confirmed in 10 cases, and the
      original CEC decisions were supported in the other 65 cases. CONCLUSIONS:
      Investigators misreport MI end points, but most later agree with CEC assessments.
      These data support standard, independent adjudication of suspected MIs for
      accurate reporting, which may affect evaluations of therapies, sample-size
      calculations, and event-rate comparisons across trials.

PMID- 11835027
TI  - Effect of intravenous testosterone on myocardial ischemia in men with coronary
      artery disease.
AB  - BACKGROUND: Studies on the effect of estrogen on atherosclerotic coronary artery
      disease (CAD) risk in women have produced conflicting results. Similar confusion,
      but fewer data, exists on the effect of testosterone on CAD risk in men. METHODS:
      We used 99mTc sestamibi single-photon emission computed tomography (SPECT)
      myocardial perfusion imaging to examine the acute effect of intravenous
      testosterone in 32 men (mean age, 69.1 +/- 6.4 years) with provocable myocardial
      ischemia on standard medical therapy. Patients performed 3 exercise (n = 18) or
      adenosine (n = 16) stress tests during the infusion of placebo or 2 doses of
      testosterone designed to increase testosterone 2 or 6 times baseline. RESULTS:
      Serum testosterone increased 137 +/- 58% and 488 +/- 113%, and estradiol levels
      increased 27 +/- 46% and 76 +/- 57%, (P <.001 for all) during the 2 testosterone
      infusions. There were no differences among the placebo or testosterone groups in
      peak heart rate, systolic blood pressure, maximal rate pressure product,
      perfusion imaging scores, or the onset of ST-segment depression. CONCLUSIONS:
      Acute testosterone infusion has neither a beneficial nor a deleterious effect on
      the onset and magnitude of stress-induced myocardial ischemia in men with stable
      CAD.

PMID- 11835028
TI  - Impact of body iron status on myocardial perfusion, left ventricular function,
      and angiographic morphologic features in patients with hypercholesterolemia.
AB  - BACKGROUND: Previous studies have shown that the effects of iron stores on
      atherogenesis through promotion of free radical formation and low-density
      lipoprotein (LDL) oxidation largely depend on the state of hypercholesterolemia
      (HCL) in animal models. A synergistic association of serum ferritin and LDL
      cholesterol with the risk of myocardial infarction has also been observed in
      humans. METHODS: We sought to assess the relationship of serum iron parameters to
      myocardial perfusion and wall motion abnormalities and to the extent of
      angiographic coronary artery disease (CAD) in patients with HCL. Sixty-eight male
      patients (mean age 58 +/- 9 years) with hypercholesterolemia (LDL cholesterol
      >130 mg/dL) who had never been treated and 52 normocholesterolemic male subjects
      of similar age underwent coronary angiography and exercise technetium-99m
      sestamibi gated single-photon emission computed tomography imaging within 10
      days. RESULTS: Serum ferritin had a significant correlation with the perfusion
      index (r = 0.70, P <.001), the reversibility index (r = 0.68, P <.01), and the
      wall motion index (r = 0.54, P <.05), whereas a relatively weak correlation was
      observed between total iron binding capacity and perfusion index (inversely) (r =
      -0.59, P <.01) in patients with HCL. Iron parameters were not associated with
      either perfusion or wall motion indices in the normocholesterolemic group.
      Stepwise multiple regression analysis confirmed these results. Ferritin was a
      strong determinant of perfusion in patients with HCL only (beta =.55, P =.002).
      Iron parameters were not related to the angiographic extent of CAD as defined by
      angiographic vessel or extent score in either group. CONCLUSIONS: Our data
      suggest that increased iron stores are closely associated with a greater extent
      and severity of perfusion and functional abnormalities but not with the
      angiographic extent of CAD in patients with HCL. Enhanced iron-mediated oxidative
      stress and LDL peroxidation may contribute to the hypercholesterolemia-related
      endothelial dysfunction and cause further impairment of myocardial perfusion and
      wall motion.

PMID- 11835029
TI  - Early ST-segment recovery, infarct artery blood flow, and long-term outcome after
      acute myocardial infarction.
AB  - BACKGROUND: Early resolution of ST-segment deviation (ST recovery) on the
      postthrombolytic electrocardiograms and restoration of "normal" blood flow in the
      infarct-related artery are associated with improved outcomes after myocardial
      infarction (MI). METHODS AND RESULTS: To evaluate the relationships between ST
      recovery, infarct-related artery flow, and late survival we studied 766 patients
      with electrocardiograms recorded at a median of 167 minutes after thrombolytic
      therapy. Angiography was performed at 3 weeks, and follow-up was done at a median
      of 6.3 years (interquartile range [IQR] 5.0-8.4). At 10 years, the survival rates
      were 55% (95% CI 43-70) in patients with <30% ST recovery in the single lead with
      maximum ST elevation, 71% (95% CI 64-79) in those with 30% to 70% ST recovery,
      and 74% (95% CI 68-82) in those with >70% ST recovery (P =.0005), whereas ST
      recovery measured as the sum of voltage changes of either ST deviation (elevation
      or depression) or ST elevation was not associated with 10-year survival (log-rank
      test, P =.06 and P =.34, respectively). In patients with Thrombolysis In
      Myocardial Infarction (TIMI) grade 3 flow, ST recovery of >70% (vs <30% and 30%
      to 70%) in the lead with maximum ST elevation was associated with increased late
      survival (P =.04). On multivariate analysis, the predictors, at admission, of 5
      year survival were age (P <.001), ST recovery (measured as a continuous variable,
      P =.001), diabetes (P =.003) and female gender (P =.02). When the ejection
      fraction (P =.003) and TIMI flow grade (P =.02) at 3 weeks were included in the
      analysis, the P value for ST recovery was.08. CONCLUSIONS: ST recovery measured
      in the single lead with maximum ST elevation was a predictor of late survival,
      even in patients with TIMI grade 3 flow but ST recovery measured as the sum of
      voltage changes in all leads with ST deviation was not. This simple
      electrocardiographic parameter can identify patients with a reduced chance of
      survival who might benefit from additional therapies.

PMID- 11835030
TI  - Hepatocyte growth factor as a potential predictor of the presence of
      atherosclerotic aorto-iliac artery disease.
AB  - BACKGROUND: Hepatocyte growth factor (HGF), a member of the endothelial-specific
      growth factors with the greatest mitogenic activity, may play a role in the
      protection and/or repair of vascular endothelial cells injured by
      atherosclerosis. As a result, plasma HGF concentration may increase in response
      to endothelial cell damage. To test this hypothesis, we measured plasma
      concentrations of HGF in patients with or without aorto-iliac artery
      atherosclerotic disease. METHODS: One hundred ten consecutive patients who
      underwent coronary angiography were enrolled in this study. Abdominal aortography
      was performed after coronary arteriography to determine whether aorto-iliac
      artery atherosclerotic disease was present. Peripheral venous blood samples were
      obtained to measure the plasma HGF concentration. RESULTS: Aortography revealed
      aorto-iliac atherosclerotic disease in 35 patients (32%). The plasma HGF
      concentration was significantly higher in patients with arteriosclerotic lesions
      (0.35 +/- 0.11 ng/mL) than in patients without atherosclerotic lesions (0.27 +/-
      0.09 ng/mL, P =.0002). On the basis of multiple logistic regression analysis of
      the relationships between coronary risk factors, age, sex, severity of coronary
      artery disease, plasma HGF concentration, and the presence of arteriosclerotic
      lesions, plasma HGF concentration (P =.0005) and age (P =.035) were found to
      predict independently the presence of aorto-iliac arteriosclerosis. CONCLUSION:
      Plasma HGF concentration can be used to predict the presence of arteriosclerotic
      lesions in the region from the abdominal aorta to the femoral arteries.

PMID- 11835031
TI  - Fibrinogen: associations with cardiovascular events in an outpatient clinic.
AB  - BACKGROUND: Fibrinogen, known to influence the coagulation process, is an
      independent risk factor for coronary artery disease (CAD). However, its
      association with myocardial infarction (MI) and its predictive potential for
      short-term mortality, in an ongoing clinical practice, has not been
      characterized. OBJECTIVES: In a high-risk outpatient practice we sought to
      demonstrate whether baseline fibrinogen levels related to MI rather than CAD
      alone, and whether baseline serum fibrinogen levels predicted mortality over a
      short-term follow-up. METHODS AND RESULTS: From a total of 2126 patients with
      baseline fibrinogen measurements (mean age, 56 +/- 12 years, 35% female), 1187
      patients with CAD (n = 606 with MI) and 939 patients without CAD were evaluated
      in an active preventive cardiology unit of a large city hospital. Logistic
      regression models were used to determine the association of fibrinogen with
      differing CAD presentations. Fibrinogen quartile showed a significant correlation
      with CAD both univariately and after adjustment for Framingham risk score (odds
      ratio [OR] = 1.22, P <.001). Fibrinogen levels were significantly associated with
      the presence of CAD and history of MI (adjusted OR = 1.25, P =.001). Fibrinogen
      did not show a significant association to CAD when MI was not considered in the
      analysis (OR = 1.01, P =.82). In this same clinical cohort, after a mean follow
      up of 24 +/- 13 months, 41 patients had died. Consistent with the observed
      association with MI, fibrinogen quartile showed a graded independent relation to
      mortality in a cohort of both men and women (hazard ratio = 1.81, P <.001).
      CONCLUSIONS: In the clinical setting of an outpatient clinic, fibrinogen was
      directly associated with the presence of MI and was revealed to be an independent
      short-term predictor of mortality.

PMID- 11835032
TI  - Typical symptoms are predictive of acute coronary syndromes in women.
AB  - BACKGROUND: Previous research suggests that the presentation of acute coronary
      syndromes (ACS) may differ in women and men. No study has prospectively evaluated
      the role of a comprehensive set of typical and atypical symptoms and whether
      different symptoms on presentation predict ACS diagnosis in women and men.
      METHODS AND RESULTS: We directly observed 246 women and 276 men seen in the
      emergency department with symptoms suggestive of ACS and documented their
      symptoms verbatim. ACS was eventually diagnosed in 89 (36%) women and 124 (45%)
      men on the basis of standard electrocardiogram and cardiac enzyme criteria.
      Presence of typical symptoms (chest pain or discomfort, dyspnea, diaphoresis, and
      arm or shoulder pain) was significantly associated with a diagnosis of ACS in
      women but not in men. On the other hand, atypical symptoms were not related to
      ACS diagnosis in women, whereas in men some atypical symptoms (dizziness or
      faintness) were inversely associated with ACS (P =.007). In multivariate
      analysis, the only symptoms that showed significant or borderline associations
      with ACS in women were diaphoresis (P =.019) and chest pain or discomfort (P
      =.069). Chest pain or discomfort and other typical symptoms were not
      significantly associated with ACS in men. Adjusted relative risks for ACS
      associated with the presence of typical symptoms in women compared with men were
      close to 1.0, indicating no sex differences. CONCLUSIONS: Typical symptoms are
      the strongest symptom predictors of ACS in women, and they are as important in
      women as in men. Clinicians need to take very seriously any woman who has typical
      symptoms and pursue a full cardiac work-up.

PMID- 11835033
TI  - Chronologic electrocardiographic changes in patients with hypertrophic
      cardiomyopathy associated with cardiac troponin 1 mutation.
AB  - BACKGROUND: Deletion of lysine 183 (K183del) in the cardiac troponin I (cTnI)
      gene is one of the mutations that causes hypertrophic cardiomyopathy (HCM).
      However, the phenotypic expression of this mutation has not been well
      established. METHODS AND RESULTS: We analyzed 10 probands with HCM associated
      with a K183del in the cTnI gene, as well as their family members. Forty-seven of
      these 80 subjects were found to be carriers and 33 were noncarriers. In the
      carrier subjects, electrocardiogram (ECG) abnormalities were initially noted
      during the early teenage years preceding echocardiographic abnormalities.
      Abnormal Q waves were found first and most frequently compared with other ECG
      abnormalities. Abnormal Q waves were frequently observed in leads II, III, aVF,
      V5, and V6 in teenage patients, whereas they were observed in many leads in
      patients >20 years old. The youngest of the 11 patients who had sudden cardiac
      death among studied pedigrees was a 14-year-old boy. CONCLUSIONS: These results
      suggest that the first phenotypic manifestation in patients with HCM associated
      with a K183del mutation in the cTnI gene is abnormal Q waves in leads II, III,
      aVF, V5, and V6 during the early teenage years. To prevent sudden death in family
      members of patients with this mutation, it may be necessary to genetically
      diagnose it before age 10 years and to pay careful attention to any development
      of abnormal Q waves.

PMID- 11835034
TI  - Antibiotics against Chlamydia pneumoniae and prognosis after acute myocardial
      infarction.
AB  - BACKGROUND: There is mounting pathologic and immunologic evidence that Chlamydia
      pneumoniae plays a role in the atherogenic pathway. However, very few clinical
      studies have supported these findings. METHODS: Using the administrative data of
      all patients > or =65 years of age who had an acute myocardial infarction (AMI)
      in Quebec between 1991 and 1995 (n = 26,195), we studied the relationship between
      the intake of antichlamydial antibiotics and post-AMI prognosis. Three groups
      were compared: patients exposed to (1) antichlamydial antibiotics, (2) sulfa
      derivative antibiotics, to which C pneumoniae is not sensitive, and (3) neither
      of the above classes of antibiotics. Two periods of antibiotic exposure were
      explored: (1) during the first 3 months after AMI and (2) during the 6 months
      before AMI. RESULTS: Patients in the 3 exposure groups were similar except for a
      slightly lower proportion of men in the sulfa-derivative antibiotics group. Among
      all patients who were exposed during the 3 months after AMI and who survived at
      least 3 months, the 1-year mortality rate was similar across the 3 groups (10.1%,
      11.1%, and 10.4% for the antichlamydial, sulfa-derivative, and nonexposed group,
      respectively) but favored the antichlamydial group at 2 years (15.9%, 23.0%, and
      20.0%). In adjusted survival analysis, patients in the sulfa-derivative and
      nonexposed groups were slightly more likely to die than patients in the
      antichlamydial group (relative risk [RR], 1.38; 95% confidence interval [CI],
      1.04 to 1.82 and 1.29; 95% CI, 1.05 to 1.59, respectively). Among individuals
      treated during the 6 months before AMI, the adjusted risk of dying was similar in
      the sulfa-derivative and nonexposed groups compared with the antichlamydial group
      (RR 1.03, 95% CI 0.90 to 1.18 and 1.08, 95% CI 0.99 to 1.19, respectively).
      CONCLUSIONS: Exposure to antichlamydial antibiotics during the 3 months after AMI
      is associated with a small survival benefit, whereas exposure during the 6 months
      before AMI does not affect survival.

PMID- 11835035
TI  - Bisoprolol for the treatment of chronic heart failure: a meta-analysis on
      individual data of two placebo-controlled studies--CIBIS and CIBIS II. Cardiac
      Insufficiency Bisoprolol Study.
AB  - BACKGROUND: Despite the available evidence from randomized clinical trials, beta
      blockers are often not used optimally in patients with congestive heart failure
      (CHF). This meta-analysis aims at providing a precise and quantitative estimate
      of the benefit and risks of long-term bisoprolol on major clinical events in
      patients with CHF, both overall and in selected subgroups. This may help
      clinicians in their decisions as to whether to prescribe bisoprolol for their
      individual patients. METHODS: Meta-analysis was performed of results from the 2
      randomized, controlled clinical studies in which bisoprolol was compared with
      placebo (Cardiac Insufficiency Bisoprolol Study [CIBIS and CIBIS II]), which
      included 3288 patients with proven CHF. The main outcomes were total death,
      cardiovascular death, sudden death, hospitalization for heart failure, and
      myocardial infarction. RESULTS: A highly significant 29.3% relative reduction of
      death (17%, 40%; P =.00003) was observed, as well as significant risk reduction
      in cardiovascular death and sudden death in favor of bisoprolol. Also, a highly
      significant relative reduction of 18.4% (25%, 11%; P =.00001) in hospital
      admission or death was observed. A similar relative reduction of death was
      consistently observed in selected subgroups of patients. CONCLUSIONS: Bisoprolol
      prevents major cardiovascular events in patients with CHF with a high benefit-to
      risk ratio and can be recommended for these patients.

PMID- 11835036
TI  - Prognostic impact of workload in patients with congestive heart failure.
AB  - AIMS: Recent data underline the prognostic value of cardiopulmonary exercise
      parameters (eg, peak oxygen consumption [PVO2]), percentage of predicted oxygen
      consumption [ppVO2], ventilation, and workload) in patients with congestive heart
      failure. These parameters were not yet compared in a multivariate analysis.
      METHODS AND RESULTS: To detect the superiority of one of these parameters, in a
      prospective 1-year follow-up study we investigated 226 patients with heart
      failure. The end point of the study was combined death and prioritization for
      urgent cardiac transplantation within 1 year. Cardiopulmonary exercise testing
      was performed with evaluation of peak oxygen consumption, percentage of predicted
      peak oxygen consumption, peak carbon dioxide production, ventilation, workload,
      anaerobic threshold, and ventilation/carbon dioxide production ratio. All
      variables were univariate predictors of 1-year mortality and urgent
      transplantation. Multivariate analysis demonstrated that only workload and
      ventilation were independently related to 1-year mortality and urgent cardiac
      transplantation, whereas peak oxygen consumption or percentage of predicted peak
      oxygen consumption did not reach statistical significance in this model.
      CONCLUSION: Workload on bicycle stress test correlates to 1-year mortality. More
      important, workload is a more powerful predictor of 1-year survival compared with
      established markers such as pVO2 or ppVO2.

PMID- 11835037
TI  - Acute blood pressure response to trandolapril and captopril in patients with left
      ventricular dysfunction after acute myocardial infarction.
AB  - OBJECTIVE: Our purpose was to compare the blood pressure response to short-term
      treatment with captopril or trandolapril in patients with left ventricular (LV)
      dysfunction after acute myocardial infarction (AMI). METHODS: A multicenter,
      randomized, double-blind, double-dummy, parallel group study was performed.
      Treatment was initiated 3 to 10 days after the onset of symptoms. On day 1,
      patients received a single dose of captopril 6.25 mg, trandolapril 0.5 mg, or
      placebo in the morning. Treatment was then titrated upward over the next 5 days.
      Blood pressure was monitored with an automated device for the first 12 hours
      after dosing on day 1. Conventional blood pressure measurements were performed
      throughout the study. RESULTS: Of 205 patients treated in the study, 193 patients
      were evaluated for first-dose effects. In the captopril group, the maximum
      decrease in blood pressure occurred after 2 hours, and the magnitude of this
      decrease was significantly greater than in the other 2 groups: 8.8 +/- 12/6.3 +/-
      8 mm Hg (captopril) versus 5.4 +/- 10/3.1 +/- 8 mm Hg (trandolapril) versus 2.4
      +/- 9/1.4 +/- 7 mm Hg (placebo) (P <.01). In the trandolapril group, the maximum
      decrease occurred after 7 hours and the magnitude of this effect was similar in
      all 3 groups: 5.9 +/- 11/3.6 +/- 8 mm Hg (trandolapril) versus 4.3 +/- 10/3.5 +/-
      8 mm Hg (captopril) versus 3.1 +/- 11/2.8 +/- 8 mm Hg (placebo) (not
      significant). Although there was a higher incidence of hypotension on day 1 in
      the captopril group, the overall incidence of hypotension during the study period
      was similar in both active treatment groups. CONCLUSION: Because of differences
      in initial blood pressure response profiles, short-term treatment with
      trandolapril tended to be better tolerated than captopril in post-AMI patients
      with LV dysfunction.

PMID- 11835038
TI  - Urine albumin/creatinine ratio and echocardiographic left ventricular structure
      and function in hypertensive patients with electrocardiographic left ventricular
      hypertrophy: the LIFE study. Losartan Intervention for Endpoint Reduction.
AB  - BACKGROUND: Albuminuria, reflecting systemic microvascular damage, and left
      ventricular (LV) geometric abnormalities have both been shown to predict
      increased cardiovascular morbidity and mortality. However, the relationship
      between these markers of cardiovascular damage has not been evaluated in a large
      hypertensive population. METHODS: The urine albumin/creatinine ratio (UACR) and
      echocardiographic measures of LV structure and function were obtained in 833
      patients with stage I to III hypertension and LV hypertrophy determined by
      electrocardiogram (ECG) (Cornell voltage-duration or Sokolow-Lyon voltage
      criteria) after 14 days of placebo treatment. RESULTS: Patients' mean ages were
      66 years, 42% were women, 23% had microalbuminuria, and 5% had macroalbuminuria.
      Patients with eccentric or concentric LV hypertrophy had higher prevalences of
      microalbuminuria (average 26%-30% vs 9%, P <.001) and macroalbuminuria (6%-7% vs
      <1%, P <.001). Furthermore, patients with microalbuminuria and macroalbuminuria
      had a significantly higher LV mass and lower endocardial and midwall fractional
      shortening. Patients with abnormal diastolic LV filling parameters had a
      significantly increased prevalence of microalbuminuria. In univariate analyses,
      UACR correlated positively to LV mass, systolic blood pressure, age (all P <.001)
      and pulse pressure/stroke volume and negatively to relative wall thickness (both
      P <.01) and endocardial (P <.05) and midwall shortening (P <.001) but not to
      diastolic filling parameters. In multiple regression analysis higher UACR was
      associated with higher LV mass (beta=.169, P <.001) independently of older age
      (beta =.095, P <.01), higher systolic pressure (beta=.163), black race
      (beta=.186), and diabetes (beta=.241, all P <.001). CONCLUSIONS: In hypertensive
      patients with ECG LV hypertrophy, abnormal LV geometry and high LV mass are
      associated with high UACR independent of age, systolic blood pressure, diabetes,
      and race, suggesting parallel cardiac and microvascular damage.

PMID- 11835039
TI  - Impact of geographic miss on adjacent coronary artery segments in diffuse in
      stent restenosis with beta-radiation therapy: angiographic and intravascular
      ultrasound analysis.
AB  - BACKGROUND: The impacts of geographic miss on edge restenosis have not been
      sufficiently evaluated. METHODS: Beta-radiation therapy with rhenium 188-filled
      balloon after rotational atherectomy for diffuse in-stent restenosis was
      performed in 50 patients. We evaluated the impacts of geographic miss on adjacent
      coronary artery segments beyond the stent by angiographic (QCA) and intravascular
      ultrasound (IVUS) analysis in 50 irradiated lesions and 100 edges. Serial IVUS
      and QCA comparisons between postradiation and 6 months' follow-up were available
      in 44 and 47 of 50 patients, respectively. QCA measurements of minimal lumen
      diameter (MLD) and IVUS analysis were performed in the reference and radiation
      segments. Edges that were touched by the angioplasty balloon but were not
      adequately covered by radiation constituted the geographic miss edges. RESULTS:
      Geographic miss was observed in 55.6% and 52.6% in QCA and IVUS analysis,
      respectively. Edge restenosis after radiation therapy in 3 patients was
      associated with geographic miss. In contrast to uninjured edges (postradiation
      2.9 +/- 0.6 mm to follow-up 2.8 +/- 0.6 mm, P =.292), MLD in the radiation
      segment by QCA analysis significantly decreased from 2.7 +/- 0.4 mm to 2.4 +/-
      0.6 mm in geographic miss edges (P =.002). IVUS analysis showed that significant
      positive remodeling in the radiation segment occurred in uninjured edges (vessel
      area from 15.4 +/- 4.4 mm2 to 15.8 +/- 4.4 mm2, P =.001) but not in geographic
      miss edges (vessel area from 12.8 +/- 3.6 mm2 to 13.0 +/- 3.6 mm2, P =.119).
      CONCLUSION: The geographic miss might be one of the predictors, which resulted in
      decreased MLD at follow-up in beta-radiation therapy. Sufficient lesion coverage
      with radiation might be associated with positive remodeling in the radiation
      segment.

PMID- 11835040
TI  - Abciximab improves 6-month clinical outcome after rescue coronary angioplasty.
AB  - BACKGROUND: Few data are available concerning the effects on clinical outcome and
      left ventricular function of abciximab administration in patients undergoing
      rescue percutaneous transluminal coronary angioplasty (PTCA) after failed
      thrombolysis for acute myocardial infarction. The aim of the study was to
      investigate such effects. METHODS: Eighty-nine consecutive patients referred to
      our laboratory from other hospitals for rescue PTCA within 24 hours from the
      onset of chest pain were prospectively randomized before the procedure to
      abciximab treatment (44 patients) or placebo (45 patients). No significant
      differences in baseline characteristics were observed between the 2 groups. Study
      end points were the occurrence of major adverse cardiac events (MACE) such as
      death, reinfarction, congestive heart failure, target lesion revascularization,
      or recurrent ischemia at 30-day and 6-month follow-up and the occurrence of
      periprocedural bleeding. RESULTS: Mean time from symptom onset to reperfusion was
      8.5 +/-5.4 hours; rescue PTCA was successful in 96% of patients. The incidence of
      major, moderate, and minor bleeding was similar in the 2 groups. At 30-day follow
      up, the echocardiographic left ventricular wall motion score index showed a
      significantly higher improvement in the abciximab group versus the placebo group
      (P <.001). At 6-month follow-up, the incidence of MACE was 11% in the abciximab
      group versus 38% in the placebo group (P =.004). Abciximab administration (P
      =.003) and cardiogenic shock (P =.005) were the only independent predictors of
      the occurrence of MACE at multivariable analysis. CONCLUSION: Treatment with
      abciximab during rescue PTCA positively affects clinical outcome at 6-month
      follow-up without increasing periprocedural bleeding.

PMID- 11835041
TI  - Centered versus noncentered source for intracoronary artery radiation therapy: a
      model based on the Scripps Trial.
AB  - BACKGROUND: The Scripps Trial was a randomized study of intracoronary artery
      radiation therapy with iridium 192 used to treat restenotic vessels. We used the
      intravascular ultrasound data from the Scripps Trial to investigate whether a
      lumen-centered gamma or beta radiation source would reduce radiation dose
      heterogeneity compared with the noncentered source position used. METHODS:
      Analysis included 28 patients with stent placement in 20 native vessels and 8
      saphenous vein grafts enrolled in this trial. Radiation dosimetry for gamma
      radiation was calculated to deliver 800 cGy to the far field target, provided the
      maximum dose to the near field target did not exceed 3000 cGy. Prescribed
      dosimetry for beta radiation by use of yttrium 90 was 1600 cGy at 2 mm distance
      from the source. RESULTS: The calculated average minimum source to target
      distance by use of a lumen-centered source increased by 0.18 mm from 1.70 +/-
      0.25 to 1.88 +/- 0.36 mm, whereas the maximum distance decreased by 0.17 mm from
      3.64 +/- 0.60 to 3.47 +/- 0.43 mm (P <.05). On the basis of these distances, the
      maximum radiation dose, as well as radiation dose heterogeneity (ratio of maximum
      to minimum), would have been reduced in 22 of 28 patients by use of a lumen
      centered gamma or beta source (P <.005). The reduction in dose heterogeneity was
      substantially greater with a beta source compared with a gamma source (48% vs 16%
      reduction). CONCLUSIONS: Centering of the intracoronary artery radiation therapy
      delivery catheter within the vessel lumen can significantly reduce radiation dose
      heterogeneity when compared with a noncentered source position. This dose
      reduction is substantially greater for a beta compared with a gamma source.

PMID- 11835042
TI  - Improvements in blood rheology after cardiac rehabilitation and exercise training
      in patients with coronary heart disease.
AB  - OBJECTIVES: Our purpose was to examine the effect of cardiac rehabilitation and
      exercise training on blood rheology in patients with coronary heart disease
      (CHD). Although increased blood and plasma viscosity have been associated with an
      increased risk of CHD, the effects of cardiac rehabilitation and exercise
      training on blood rheology in patients with CHD are uncertain. METHODS: We
      assessed whole blood effective viscosity (mu), hematocrit standardized blood
      viscosity (mu45)), red blood cell transport efficiency (tau(rbc)), and plasma
      viscosity (PV) in 23 nonsmoking patients with CHD before and after a phase II
      cardiac rehabilitation and exercise training program. In addition, we compared
      the group data with the data of a healthy reference group of 10 subjects.
      RESULTS: Patients with CHD had significantly elevated mu (3.35 +/- 0.35 cp vs
      3.06 +/- 0.19 cp, P <.05) and mu45 (3.51 +/- 0.29 cp vs 3.12 +/- 0.06 cp, P
      <.001) and reduced tau(rbc) (12.7% +/- 1.0% x cp(-1) vs 14.2% +/- 0.7% x cp(-1),
      P <.001) compared with healthy subjects. After rehabilitation, patients with CHD
      had reductions in PV (1.85 +/- 0.18 cp vs 1.77 +/- 0.11 cp, P <.01) and mu45
      (3.58 +/- 0.22 cp vs 3.39 +/- 0.22 cp, P <.0001) and an increase in tau(rbc)
      (12.4% +/- 0.8% x cp(-1) vs 13.2% +/- 0.9% x cp(-1), P <.0001). CONCLUSIONS:
      Cardiac rehabilitation improves blood rheology in patients with CHD by reducing
      mu45 and PV and elevating tau(rbc). These improvements may contribute to the
      increased functional capacity and reduced morbidity and mortality that is
      associated with participation in cardiac rehabilitation and exercise programs.

PMID- 11835043
TI  - Policosanol: clinical pharmacology and therapeutic significance of a new lipid
      lowering agent.
AB  - BACKGROUND: Policosanol is a mixture of higher primary aliphatic alcohols
      isolated from sugar cane wax, whose main component is octacosanol. The mixture
      has been shown to lower cholesterol in animal models, healthy volunteers, and
      patients with type II hypercholesterolemia. METHODS: We reviewed the literature
      on placebo-controlled lipid-lowering studies using policosanol published in peer
      reviewed journals as well as studies investigating its mechanism of action and
      its clinical pharmacology. RESULTS: At doses of 10 to 20 mg per day, policosanol
      lowers total cholesterol by 17% to 21% and low-density lipoprotein (LDL)
      cholesterol by 21% to 29% and raises high-density lipoprotein cholesterol by 8%
      to 15%. Because higher doses have not been tested up to now, it cannot be
      excluded that effectiveness may be even greater. Daily doses of 10 mg of
      policosanol have been shown to be equally effective in lowering total or LDL
      cholesterol as the same dose of simvastatin or pravastatin. Triglyceride levels
      are not influenced by policosanol. At dosages of up to 20 mg per day, policosanol
      is safe and well tolerated, as studies of >3 years of therapy indicate. There is
      evidence from in vitro studies that policosanol may inhibit hepatic cholesterol
      synthesis at a step before mevalonate generation, but direct inhibition of the
      hydroxy-methylglutaryl-coenzyme A reductase is unlikely. Animal studies suggest
      that LDL catabolism may be enhanced, possibly through receptor-mediated
      mechanisms, but the precise mechanism of action is not understood yet.
      Policosanol has additional beneficial properties such as effects on smooth muscle
      cell proliferation, platelet aggregation, and LDL peroxidation. Data on efficacy
      determined by clinical end points such as rates of cardiac events or cardiac
      mortality are lacking. CONCLUSIONS: Policosanol seems to be a very promising
      phytochemical alternative to classic lipid-lowering agents such as the statins
      and deserves further evaluation.

PMID- 11835044
TI  - Use of an implantable loop recorder in the evaluation of children with congenital
      heart disease.
AB  - BACKGROUND: A recently developed implantable loop recorder (ILR) has been used in
      adult patients whose syncope remains unexplained in spite of extensive
      investigations. Syncope in the patient with congenital heart disease presents a
      diagnostic challenge. We applied this technology to a cohort of pediatric
      patients. METHODS: We reviewed our experience with an ILR in patients with
      congenital heart disease with syncope or palpitations after conventional
      investigations failed to identify a cause for the symptoms. RESULTS: ILRs were
      implanted in 4 patients with congenital heart disease at 2 centers for
      investigation of syncope (n = 2), near-syncope (n = 1), and palpitations (n = 1).
      Implantations were performed at a mean age of 5.9 +/- 0.9 years (4.2 to 7.6
      years) and a mean weight of 26.7 +/- 6.6 kg (15.7 to 42.5 kg) with patients under
      general anesthesia, with no complications. All patients experienced typical
      symptoms and activated the device appropriately at a median of 86 days (46 to
      102) after implantation. Each patient had good-quality data that allowed
      interpretation of the rhythm. In 2 of 4 cases, a likely cause for the symptoms
      was identified, with exclusion of more malignant arrhythmic diagnoses in all
      patients. Escalation of therapy was avoidable in all patients on the basis of the
      data recorded by the ILR. CONCLUSIONS: Recently developed loop recorder
      technology can be implanted in the young child without difficulty. The ILR proved
      to be very useful for excluding malignant arrhythmias as a cause of symptoms in
      these patients at high risk.

PMID- 11835048
TI  - Localizing the EGF receptor.

PMID- 11835050
TI  - Limits to lifespan.
AB  - It has long-been accepted that normal somatic cells have intrinsic mechanisms
      that limit their proliferative lifespan. Recent work has now challenged this view
      by demonstrating that extrinsic factors might be determining proliferative
      potential.

PMID- 11835051
TI  - Formin' actin filament bundles.

PMID- 11835052
TI  - Hip, hip, hippi!

PMID- 11835053
TI  - Ignition of a cellular machine.

PMID- 11835054
TI  - 'Rab'ing up endosomal membrane transport.

PMID- 11835055
TI  - Proteomics of the nucleolus.

PMID- 11835058
TI  - Establishing cell polarity in development.
AB  - Polarity is a common feature of many different cell types, including the
      Caenorhabditis elegans zygote, the Drosophila oocyte and mammalian epithelial
      cells. The initial establishment of cell polarity depends on asymmetric cues that
      lead to reorganization of the cytoskeleton and polarized localization of several
      cortical proteins that act downstream of the polarization cues. The past year
      revealed that homologs of the C. elegans par (partitioning defective) genes are
      also essential for establishing polarity in Drosophila and vertebrate cells.
      There is growing evidence that the proteins encoded by these genes interact with
      key regulators of both the actin and the microtubule cytoskeletons.

PMID- 11835059
TI  - To Begin Again.

PMID- 11835060
TI  - The Interaction of Hydrochlorothiazide with Spirapril: A Novel Ace Inhibitor.
AB  - In an open-label, randomized trial using a 3 x 3 Latin square design, single
      doses of 24 mg of the ACE inhibitor spirapril, or 50 mg hydrochlorothiazide, or
      their combination were given to 18 healthy male volunteers. No alteration in the
      area under plasma drug concentration curve (AUC), peak plasma level, time to peak
      level, or elimination half-life was detected for hydrochlorothiazide, spirapril,
      or its active metabolite, spiraprilat, during combination therapy. It was
      concluded that there was no significant effect of spirapril on single-dose
      kinetics of hydrochlorothiazide, nor of hydrochlorothiazide on single-dose
      kinetics of spirapril. Significant reductions in systolic blood pressure were
      noted 2--6 h after either spirapril or combination treatment, but no evidence of
      any synergistic effect of single-dose effects on blood pressure was seen during
      combination therapy.

PMID- 11835061
TI  - The Effect of Cromakalim on the Hindlimb Vascular Bed of the Male Rat: Do
      Glybenclamide and/or Nitric Oxide Modulate the Vasodilation?
AB  - Cromakalim, a benzopyran derivative, is a member of a novel class of
      antihypertensive agents that increase membrane K(+) conductance through ATP
      sensitive K(+) channels. The effects of glybenclamide and N(omega)-L-arginine
      methyl ester (L-NAME), a specific inhibitor of nitric oxide synthesis from L
      arginine were investigated on the vasodilator response to cromakalim in the
      hindlimb vascular bed in the male rat, as well as the combination glybenclamide
      and L-NAME. Thirty male Sprague--Dawley rats (350--450 g) were studied.
      Cromakalim in three doses (10, 30, 100 &mgr;g) injected into the hindlimb through
      a catheter induced a significant dose-dependent decrease in both mean arterial
      pressure (MAP) and hindlimb perfusion pressure (HPP). These responses were
      significantly modified by either glybenclamide or L-NAME. The role of a
      combination of glybenclamide and L-NAME on the vasodilator responses to
      cromakalim, acetylcholine, and nitroglycerin were also investigated. Three doses
      of either acetylcholine, nitroglycerin, or cromakalim caused dose-dependent
      reduction in HPP of the rats. The responses to acetylcholine were significantly
      blocked by L-NAME, but the responses to nitroglycerin were not. The vasodilation
      induced by cromakalim was not only partly blocked by glybenclamide but also by L
      NAME. This blockade was significantly augmented when both glybenclamide and L
      NAME were infused. These results suggest that nitric oxide may play an important
      role in regulating hindlimb vascular tone under physiologic conditions. The data
      also suggest that nitric oxide may be an additional mediator for cromakalim
      vasodilation as well as K(APT)(+) channel activation in the hindlimb vascular bed
      of the male rat.

PMID- 11835062
TI  - Application of a Stable Isotope Technique for the Bioequivalency Study of Two
      Transdermal Nitroglycerin Systems.
AB  - A bioequivalency study of an experimental transdermal nitroglycerin system
      relative to the commercial Transderm-Nitro 0.4 mg/h system was performed on eight
      healthy volunteers by using an innovative stable isotope technique. Plasma
      clearance changes for nitroglycerin (NTG) during patch application were corrected
      with simultaneously administered intravenous infusion of (15)N-labeled
      nitroglycerin ((15)N-NTG) solution. The total amount of NTG transdermally
      absorbed (AUC x CL) during a 22-h application for the experimental system was not
      statistically different from that for the commercial system (9.7 plus minus 3.3
      versus 8.1 plus minus 2.6 mg; p = 0.41). The analysis of residual drug content in
      the used system revealed that the difference in amounts of NTG delivered from the
      experimental and commercial systems were not significant (12.2 plus minus 3.1
      versus 10.8 plus minus 3.1 mg; p = 0.29). With the isotope-labeled method, the
      absorption rate was evaluated at each time interval during the system
      application. The peak concentration values were 0.52 plus minus 0.21 mg h(minus
      sign1) at 1 h for the experimental system and 0.41 plus minus 0.15 mg h(minus
      sign1) at 2 h for commercial systems. After the peak concentrations, the
      absorption rates remained constant for both systems over the 16-h period. There
      was no statistical difference in absorption between the two systems at any
      sampling time. In this study, substantial fluctuations in the plasma
      concentrations of both NTG and (15)N-NTG were observed within and between
      subjects. In addition, the variability in plasma concentrations of NTG correlated
      well with that of (15)N-NTG for all participating subjects. The momentary changes
      of clearance, estimated from (15)N-NTG plasma data, were found to be responsible
      for the fluctuation of NTG in plasma.

PMID- 11835063
TI  - Food Enhances Bioavailability of the New Antiarrhythmic Agent Tiracizine by
      Affecting its Hepatic First-Pass Metabolism: Evidence by Serum and Urine
      Metabolite Kinetics.
AB  - The serum and urine kinetics of tiracizine, a new class I antiarrhythmic agent,
      and three of its metabolites were assessed in eight healthy extensive
      metabolizers after a single oral administration of 100 mg tiracizine in fasted
      state and after a standard breakfast. Additionally, ECG changes caused by
      tiracizine were compared between the two states. With food, the mean A(0minus
      signinfty infinity) value of the parent compound was significantly increased
      (560.7 versus 419.0 ng h ml(minus sign1)). The amount excreted unchanged in urine
      (percentage of the dose) rose significantly (2.43% versus 1.78%). However, mean
      AUC(0--32 h) and C(max) as well as urinary excretion of the 3-amino-5-methylamino
      acetyliminodibenzyl metabolite were decreased (1152.8 versus 1328.0 ng h ml(minus
      sign1), 43.6 versus 56.1 ng ml(minus sign1), and 8.59 versus 11.95%,
      respectively). Total urine recovery (sum of individual tiracizine and metabolite
      excretion) tended to decrease (31.1% versus 36.1%). Serum and urine metabolite
      kinetics indicate that food-induced enhancement of tiracizine bioavailability is
      caused by an alteration in hepatic first-pass metabolism. Reduced N-demethylation
      is considered to be the limiting step. Tiracizine-induced PQ and QRS
      prolongations in the ECG tended to be more pronounced with food. Due to the serum
      concentration dependence of these ECG alterations, food intake might alter the
      antiarrhythmic efficacy of tiracizine at higher doses. Therefore, patients should
      be advised to take tiracizine in a constant relationship to food to assure
      consistent bioavailability.

PMID- 11835064
TI  - Utilization of Cardiovascular Drugs in the Aged in a Long-Term-Care Institution
      for the Aged over a 5-Year Period 1987--1992.
AB  - A comparative study was made of the utilization of cardiovascular drugs in a long
      term-care facility for the aged for 1987 and 1992 during which the age and sex
      distributions and incidence of usage were similar. There were statistically
      significant declines in the usage of diuretics and potassium supplementation,
      digoxin, antihypertensives, antiarrhythmics, and beta blockers and a rise in the
      use of calcium-channel blockers. There was a slight fall in the use of
      antianginal drugs. The ACE inhibitors introduced after 1987 were taken by 6.1%.
      The dosages of digoxin and diuretics decreased as management was adequate and
      toxicity avoided and usage of digoxin reduced in accordance with the concept that
      digoxin is useful in failure only when left ventricular output is impaired.

PMID- 11835065
TI  - Propranolol Action in Chronically Unstable Generalized Epilepsy.
AB  - Chronically unstable generalized epilepsy (CUGE) is a disabling disease usually
      treated by ineffective association of drugs. Authors have devoted attention to
      calcium-dependent mechanisms of seizures. Calcium channel blockers have been used
      with success in the control of both experimental and clinical epilepsy. beta
      Adrenergic blockers, such as propranolol hydrochloride (PR), had been described
      to be experimentally effective in the control of epilepsy in rats and chicks, due
      to its receptor-dependent calcium channel blocking and membrane-stabilizing
      actions. We used PR in this crossover, placebo-controlled, randomized trial.
      Twelve patients with CUGE were enrolled and treated for 15 days with treatment A
      (20--40 mg PR bid) and treatment B (20--40 mg placebo); the difference in the
      total number of seizures in the two periods of treatment was compared. Patients
      treated with PR showed a 32.9% reduction (p < 0.05) in epileptic manifestations.
      The authors concluded that PR may be an effective adjunct therapy in CUGE and
      other forms of generalized epilepsy.

PMID- 11835066
TI  - Multiple-Dose Pharmacokinetics of Ceftibuten in Healthy Adults and Geriatric
      Volunteers.
AB  - The steady-state pharmacokinetics of ceftibuten, an orally active cephalosporin
      were investigated in 12 healthy male volunteers (19--38 years) and in 12
      geriatric volunteers (65--76 years). Each received one 200-mg ceftibuten capsule
      every 12 h on days 1--3 and one capsule in the morning on day 4. Plasma and urine
      samples were collected at various times on days 1--4 and assayed by high-pressure
      liquid chromatographic method for ceftibuten and ceftibuten-trans, a conversion
      product. The T(max) for ceftibuten and ceftibuten-trans occurred at about 2 and 3
      h, respectively, in both populations. The C(max) and AUC((0--12 h)) ranged from
      10.8 to 12.4 &mgr;g ml(minus sign1) and from 47.5 to 55.1 &mgr;g h ml(minus
      sign1), respectively, for normal volunteers compared to 12.9--17.5 &mgr;g
      ml(minus sign1) and 62.3--87.1 &mgr;g h ml(minus sign1), respectively, for
      geriatric volunteers. The respective values for ceftibuten-trans in normal and
      geriatric volunteers were 1.3 and 1.3 &mgr;g ml(minus sign1), respectively, and
      6.9--8.2 and 5.9--9.8 &mgr;g h ml(minus sign1). At steady state, the C(max) and
      AUC((0--12 h)) of ceftibuten-trans were about 10--11% and 13--16% those of
      ceftibuten in normal volunteers and about 8--9% and 9--11% those of ceftibuten,
      respectively, in geriatric volunteers. The accumulation factor of ceftibuten in
      normal volunteers was 1.1 as compared to 1.3 in geriatric volunteers. The
      terminal phase half-life was 2.5 h in healthy volunteers and 3.2 h in geriatric
      volunteers. Urinary excretion appeared to be the major route of elimination in
      both populations accounting for more than 90% of the dose recovered in the urine
      during the dosing interval. The results of this study demonstrate that
      ceftibuten, 200 mg given twice a day, is safe and well tolerated, is well
      absorbed, and that steady-state is achieved on days 3 and 4. There is some
      accumulation in the elderly, but dosage regimen based on age is not warranted.

PMID- 11835067
TI  - The Pharmacokinetics and Pharmacodynamics of Methylprednisolone in Chronic Renal
      Failure.
AB  - Methylprednisolone (MP) pharmacokinetics and its directly suppressive effects on
      cortisol secretion, circulating T-cells, and basophils in blood were compared in
      six chronic renal failure (CRF) subjects and six healthy controls after an IV
      administration of MP 0.6 mg kg(minus sign1) as the sodium succinate ester. The
      CRF subjects were studied between hemodialysis treatments. The total clearance of
      methylprednisolone sodium succinate (the prodrug) was reduced by 40% in CRF;
      however, the pharmacokinetics of methylprednisolone remained unchanged.
      Methylprednisolone clearance was approximately 280 ml h(minus sign1) kg(minus
      sign1) and volume of distribution was about 1.1 L kg(minus sign1). Physiological
      pharmacodynamic models were applied for the immediate effects of MP, based on the
      premise that receptor binding is followed by rapid suppression of the secretion
      of cortisol and recirculation of basophils, T-helper cells, and T-suppressor
      cells, which persist until inhibitory concentrations (IC(50)) of
      methylprednisolone disappear. The difference in IC(50) for each pharmacodynamic
      parameter was not statistically significant, suggesting no difference in the
      responsiveness of these factors to methylprednisolone in CRF. As the
      pharmacokinetics of other corticosteroids are altered in CRF, the lack of
      pharmacokinetic and pharmacodynamic changes of methylprednisolone may engender a
      therapeutic advantage for this corticosteroid in CRF.

PMID- 11835068
TI  - Clinical Efficacy and Safety of Lower-Dose Indapamide Therapy in the Treatment of
      Patients with Mild to Moderate Hypertension.
AB  - Previous clinical studies with indapamide, an indoline antihypertensive drug with
      diuretic and vasodilating activities, have shown a dose relationship associated
      with potassium loss. Two placebo-controlled, randomized, double-blind, parallel
      clinical studies were, therefore, done to evaluate the safety and efficacy of a
      low dose (1.25 mg) of indapamide and to determine if an improved safety profile
      could be produced while maintaining efficacy with a 1.25-mg dose in patients with
      mild to moderate essential hypertension. Four hundred seventeen (417) adult
      patients with mild to moderate essential hypertension (sitting diastolic blood
      pressure greater-than-or-equal 95 mmHg and less-than-or-equal 110 mmHg) were
      enrolled in two clinical studies; 209 patients were randomized to indapamide 1.25
      mg and 208 patients to placebo. Patients received single-blind placebo for a 4
      week washout period followed by an 8-week double-blind treatment period during
      which patients received either indapamide 1.25 mg or placebo. The primary
      efficacy endpoint was the mean change from baseline to week 8 in sitting
      diastolic blood pressure. Secondary efficacy variables were the proportion of
      patients whose sitting diastolic blood pressure had decreased greater-than-or
      equal 10 mmHg and/or had a sitting diastolic blood pressure of less-than-or-equal
      90 mmHg (treatment success) at all visits and at endpoint, mean changes from
      baseline in sitting diastolic blood pressure at designated timepoints and at
      endpoint, and mean changes from baseline in standing diastolic blood pressure and
      in sitting and standing systolic blood pressure at all visits and at endpoint.
      Results of these trials were pooled in order to have a larger patient population
      in an attempt to detect trends not readily apparent with a smaller sample size.
      In the primary analysis, indapamide produced statistically significantly (p =
      0.0001) greater reductions in sitting diastolic blood pressure than placebo after
      8 weeks of therapy. In the secondary analysis, the percentage of indapamide
      treated patients who achieved treatment success after 8 weeks of therapy was
      statistically significantly (p < 0.0001) higher compared to placebo-treated
      patients. In addition, indapamide produced a statistically significantly (p =
      0.0001) superior reduction compared to placebo in sitting systolic and standing
      systolic and diastolic blood pressure after 8 weeks of therapy. The incidence of
      drug-related adverse events between patients in the indapamide and placebo groups
      was similar. There were no clinically meaningful differences in laboratory
      values, including serum potassium, between the patients in the indapamide and
      placebo groups. Low-dose (1.25 mg) indapamide proved to be safe and effective in
      the treatment of mild to moderate hypertension.

PMID- 11835069
TI  - Equal Efficacy and Improved Tolerability with 50 mg Controlled-Release Metoprolol
      Compared with 100 mg Conventional Metoprolol in Hypertensive Patients.
AB  - The clinical efficacy and tolerability of 50 mg of a new controlled-release
      formulation of metoprolol (metoprolol CR) was compared with that of a double dose
      (100 mg) of conventional immediate-release metoprolol tablets in 64 hypertensives
      in a randomized, double-blind, crossover study. At the end of a 6-week placebo
      run-in period and after each of two 8-week active treatment periods, 3-min
      bicycle exercise tests were performed at 25, 1.3, and 5 h after dose intake.
      Twenty-five hours after dose the mean supine SBP/DBP on metoprolol CR 50 mg was
      147/95 mm Hg and on conventional metoprolol 100 mg 148/94 mm Hg, respectively.
      The percentage of responders (DBP less-than-or-equal 90 mm Hg or reduction in DBP
      greater-than-or-equal 10 mm Hg) was 45% on both regimens. At 25 h after dose,
      exercise heart rate was lower on 50 mg metoprolol CR (136 versus 140 beats
      min(minus sign1); p < 0.001) than on 100 mg conventional metoprolol, whereas the
      opposite was found at 1.3 h (131 versus 107 beats min(minus sign1); p < 0.001)
      and at 5 h (131 versus 113 beats min(minus sign1); p < 0.001). In agreement with
      the more even plasma metoprolol concentration and exercise heart rate, the
      patients perceived less fatigue during exercise on 50 mg metoprolol CR at 1.3 h
      after dose, the approximate time of maximum plasma concentration for 100 mg
      conventional metoprolol. The total number of adverse events recorded on
      metoprolol CR 50 mg and conventional metoprolol 100 mg were 62 and 103,
      respectively (p < 0.01). Thus, this study has demonstrated that the new
      controlled-release formulation of metoprolol has made it possible to halve the
      dose of metoprolol and yet achieve the same blood pressure control as well as
      greater beta(1)-blockade at the end of 24-h dosing intervals. Corresponding to
      lower peak plasma metoprolol concentrations, perceived fatigue and overall
      tolerability was improved on metoprolol CR 50 mg compared to conventional
      metoprolol 100 mg.

PMID- 11835070
TI  - A Double-Blind Crossover Comparison of Nebivolol and Lisinopril in the Treatment
      of Ambulatory Hypertension.
AB  - Twenty-four-hour ambulatory blood pressure (ABP) monitoring was used as a measure
      of drug efficacy and criterion for inclusion of 29 patients with primary
      hypertension in a double-blind crossover comparison of the novel cardioselective
      beta-blocker nebivolol (2.5--10 mg) with lisinopril (10--40 mg) once daily. After
      8 weeks of therapy, both regimens reduced clinic BP to a similar and significant
      extent. Similar and significant reductions in systolic and diastolic ABP in every
      one of the 24-h periods were observed with both treatments. Moreover, the
      percentages of "BP loads" were lowered similarly from 64% to 31% and 30% with
      nebivolol and lisinopril, respectively. Furthermore, a comparable trough:peak
      ratio of 70% was obtained with both therapies. These data demonstrate that both
      once daily nebivolol and lisinopril given as monotherapies in patients with
      ambulatory hypertension provide adequate and similar clinic and ambulatory BP
      control. In addition, our findings indicate that ABP monitoring may improve the
      clinical evaluation of new antihypertensive agents.

PMID- 11835071
TI  - Effect of Bisoprolol and Atenolol on Left Ventricular Mass in Patients with
      Essential Hypertension.
AB  - A new beta-blocker, bisoprolol, was compared to atenolol for antihypertensive
      efficacy and ability to cause regression of left ventricular mass. Twenty-eight
      patients were randomized into this 8-week, double-blind, dose-escalating trial.
      Echocardiography was performed in 18 of these patients at baseline and after 8
      weeks of therapy to determine left ventricular (LV) mass indices. Both drugs
      caused a reduction in blood pressure, although bisoprolol caused a significantly
      greater reduction than did atenolol in diastolic pressure (p < 0.05) and a trend
      toward a greater reduction in systolic pressure (p < 0.096) as measured by cuff.
      Comparisons showed a significantly greater reduction in mean LV mass indices with
      bisoprolol than with atenolol (p < 0.05). A new beta-blocker, bisoprolol, was
      compared to atenolol for antihypertensive efficacy and ability to cause
      regression of left ventricular mass. Twenty-eight patients were randomized into
      this 8-week, double-blind, dose-escalating trial. Echocardiography was performed
      in 18 of these patients (bisoprolol treated = 8, atenolol treated = 10) at
      baseline and after 8 weeks of therapy to determine left ventricular (LV) mass
      indices. Both drugs caused a reduction in blood pressure, although bisoprolol
      caused a significantly greater reduction than did atenolol in diastolic pressure
      (p < 0.05) and a trend toward a greater reduction in systolic pressure (p <
      0.096) as measured by cuff (bisoprolol means: 152.6 plus minus 9.7/102.8 plus
      minus 2.8 to 134.0 plus minus 10.0/84.4 plus minus 5.6 mm Hg; atenolol means:
      158.4 plus minus 13.8/101.4 plus minus 3.5 to 148.0 plus minus 21.4/91.4 plus
      minus 5.9 mm Hg). Ambulatory blood pressure monitoring results suggested
      bisoprolol had longer effectiveness at lowering systolic pressure than did
      atenol. Comparisons showed a significantly greater reduction in mean LV mass
      indices with bisoprolol (from 110.0 plus minus 212.3 to 101.8 plus minus 22.0 g
      m(minus sign2)) than with atenolol (116.9 plus minus 25.5 to 121.7 plus minus
      22.2 g m(minus sign2)) (p < 0.05). Bisoprolol was safe and efficacious in blood
      pressure control and significantly better than atenolol in reducing LV mass.

PMID- 11835072
TI  - Current Status of Isosorbide-5-Mononitrate Therapy in Chronic Stable Angina
      Pectoris.
AB  - A review was made of all known published data on the use of isosorbide-5
      mononitrate (5-ISMN) in chronic stable angina pectoris, and efficacy in terms of
      exercise testing (bicycle or treadmill) was assessed. Adequate documentation for
      effectiveness for 12 h with steady-state treatment (2 weeks) of 5-ISMN in
      immediate-release tablets is available only with a dosage of 20 mg twice daily,
      taken 7 h apart. For other dosage regimens, efficacy has been documented for 2 or
      at most 4 h duration after dose intake. Immediate-release tablets of 40 mg are
      effective only for 2 h in steady-state treatment. These data suggest that
      tolerance develops to some immediate-release tablet regimens. A satisfactory
      explanation for this is still lacking. The possibility that a rapid plasma level
      rise is conducive to tolerance development needs to be tested. Extended-release
      tablets in strengths from 30 to 100 mg are effective for 12 h after the first
      dose. In steady-state treatment of 3--6 weeks' duration, 12-h efficacy has been
      shown only for one brand of extended-release 5-ISMN (Imdur((R))) in doses ranging
      from 60 to 240 mg taken once daily in the morning. Currently, the best
      explanation to the maintained efficacy with long-term extended-release 5-ISMN is
      that the plasma level profile allows for a sufficiently low organic nitrate level
      for a sufficiently long uninterrupted fraction of the dosage interval, occurring
      during the night when tablet intake is once daily in the morning. Twice daily
      dosage every 12 h of extended-release 5-ISMN tablets causes tolerance
      development. Tolerability is similar for both types of tablets, and overall it is
      excellent. Headache is a common symptom at initiation of treatment but wanes
      quickly. No rebound effect in the nitrate-low period has been noted with either
      regimen. Few well-controlled studies have addressed quality of life efficacy,
      that is, the influence of symptoms and signs of daily life. Many trials of those
      reviewed were of suboptimal design, and conclusions were often overstated.

PMID- 11835073
TI  - Pharmacoeconomics: These Changing Times.

PMID- 11835074
TI  - A Review of the New Cytokines: IL-4, IL-6, IL-11, and IL-12.
AB  - The interleukins function as intercellular hormones, possessing the ability to
      alter the activity of a target cell population. Interleukin-4, secreted by
      activated T-cells, has shown antitumor activity in vitro against multiple
      myelomas, lymphoma, chronic myelomonocytic leukemia, and some solid tumors. Early
      promising clinical studies have shown the efficacy of IL-4 in decreasing the
      malignant lymphocyte count and in normalizing hematologic parameters in patients
      with CLL and in inducing transient clinical responses in patients with non
      Hodgkin's lymphoma. Interleukin-6 possesses immunomodulating properties including
      enhancement of NK cell activity and induction of cytotoxic T-cell activity. IL-6
      has shown antitumor activity in mice injected with weakly immunogenic syngeneic
      tumors and has been shown to inhibit in vitro human breast carcinoma and
      leukemia/lymphoma proliferation through a direct tumor inhibitory effect.
      Clinical studies investigating the antitumor activity of IL-6 are currently in
      phase II clinical trials. IL-6 and IL-11 have demonstrated thrombopoietic
      enhancing activity in primate models and early clinical trials. These agents have
      a potential application in ameliorating the thrombocytopenia associated with
      myeloablative chemotherapy. Yet to enter clinical trials, IL-12 has been shown to
      enhance the lytic activity of nonspecific NK/LAK cells and appears to be more
      efficient than IL-2 or IFN's in enhancing NK cytotoxicity. IL-12 has also been
      shown to enhance specific allogeneic human CTL responses and to induce the
      secretion of IFN-gamma from both resting and activated T and NK cells. In
      summary, these interleukins are now promising agents under investigation as
      effective treatment strategies in the oncologic setting.

PMID- 11835075
TI  - Concentration/Effect Analysis of Antihypertensive Drugs.
AB  - Studies on the concentration/effect relationship of different antihypertensive
      agents (mainly calcium antagonists and alpha(1)-blockers) in patients confirm a
      close relation between plasma concentrations and the corresponding fall in blood
      pressure, but the heterogenity in study objectives and methodology impedes the
      compiling and differentiation of results. Concentration/effect analysis was
      established using either the linear or the E(max) model. The studies reviewed
      here do not speak unequivocally in favor of either one of the methodological
      approaches (linear or E(max) model, PK/PD modeling, placebo correction) or a
      certain mode of blood pressure measurement. The responsiveness parameters
      obtained exhibited a wide intersubject variability; thus, threshold levels
      derived for any of the investigated compounds can only be used to a limited
      extent. For drug development, a more integrated protocol should be strived for to
      design studies on concentration/effect relationship for antihypertensives.
      Although individualized dose adjustment based on concentration/effect analysis
      after single-dose application was applied successfully, this approach seems to be
      an inadequate strategy for conventional treatment of hypertension.

PMID- 11835076
TI  - Perindopril/Hydrochlorothiazide Combination in Hypertensive Patients Unresponsive
      to Hydrochlorothiazide Alone: A Double-Blind, Multicenter Study.
AB  - This study evaluated the efficacy and tolerability of perindopril erbumine, a
      long-acting ACE inhibitor, added to continuing hydrochlorothiazide (HCTZ) therapy
      in hypertensive patients (DBP of 95 to 114 mmHg) whose blood pressure did not
      normalize (supine DBP <90 mmHg) with HCTZ therapy alone. In this multicenter
      study, 252 patients received HCTZ 25 mg/day for 4 weeks; the 208 whose blood
      pressure did not normalize entered a 12-week, double-blind segment. These
      patients continued to receive HCTZ and were randomly assigned to perindopril (2,
      4, or 8 mg) or placebo once daily. Mean supine SBP/DBP reductions from baseline
      for all HCTZ plus perindopril groups were significantly (p less-than-or-equal
      0.05) greater than for HCTZ plus placebo. At the start of double-blind treatment,
      mean supine SBP/DBP readings were 146.1/97.0, 145.4/98.2 and 146.4/98.2 mmHg for
      the HCTZ plus perindopril 2-, 4-, and 8-mg groups, respectively, and 143.9/96.9
      mmHg for HCTZ plus placebo group. At the final visit, mean reductions in supine
      SBP/DBP were 10.3/6.7, 9.6/8.0, and 9.3/6.3 mmHg for HCTZ plus perindopril 2, 4,
      and 8 mg, respectively, and 1.6/2.0 mmHg for HCTZ plus placebo. Significantly (p
      less-than-or-equal 0.05) more HCTZ plus perindopril patients (53.2%) than HCTZ
      plus placebo patients (24.5%) achieved an adequate response to therapy (supine
      DBP <90 mmHg or decrease by >10 mmHg). Incidences of adverse experiences were
      similar among treatment groups. There were no reports of first-dose hypotension.
      In patients unresponsive to HCTZ alone, the addition of perindopril at doses of 2
      -8 mg once daily provided safe and effective blood pressure reduction with no
      added side-effect liability.

PMID- 11835077
TI  - The Pharmacokinetics of Once-Daily Diltiazem SR (Sustained-Release) in Young
      Versus Elderly Hypertensive Patients.
AB  - The objective of this open-label, outpatient, parallel-group investigation was to
      compare the single-dose and steady-state pharmacokinetic profiles of young (n =
      12; x = 41 +/- 6 years) and elderly (n = 12; X = 69 +/- 4 years) hypertensive
      patients following administration of a once-daily formulation of diltiazem. The
      study was comprised of two phases. The first phase was a lead-in phase used to
      establish hypertensive status. In the second phase, patients were administered a
      single- and multiple-daily dose regimen of 240 mg of diltiazem SR. Plasma samples
      were obtained at selected times and analyzed for diltiazem using a specific and
      sensitive HPLC assay. Biopharmaceutic parameter estimates were determined and
      analyzed for statistical differences. Qualitatively similar concentration-time
      profiles were observed between groups, suggesting similar release characteristics
      of the sustained-release formulation. However, significantly higher overall
      concentrations of diltiazem were observed following single-dose administration in
      the elderly, possibly as a result of an age-related decrease in the apparent oral
      clearance of diltiazem. A further reduction in the apparent oral clearance of
      diltiazem with multiple-dose administration was observed in the elderly resulting
      in even higher than projected concentrations of diltiazem. Thus, greater oral
      systemic availability of diltiazem in the elderly hypertensive patients may
      warrant closer clinical monitoring and possibly a reduction in dosage.

PMID- 11835078
TI  - Electrophysiologic Changes in the Human Heart Produced by Enalaprilat
      (Angiotensin-Converting Enzyme Inhibitor).
AB  - Several trials have showed that angiotensin-converting enzyme inhibitors possess
      some extent of antiarrhythmic properties. To evaluate the effects of Enalaprilat
      on His bundle recording, patients undergoing diagnostic coronary angiogram due to
      angina pectoris and a positive thallium exercise test subsequently underwent His
      bundle electrogram. A double-blind crossover protocol was used with conduction
      velocity measurements at baseline and after saline (placebo) and Enalaprilat 2.5
      mg intravenously. There were no significant changes in heart rate (64 plus minus
      9 versus 65 plus minus 11 versus 65 plus minus to beats min(minus sign1)) at
      baseline, after saline and enalaprilat infusion, respectively, mean blood
      pressure (97 plus minus 11 versus 94 plus minus 10 versus 94 plus minus 7 mm Hg,
      respectively), atrioventricular conduction time (100 plus minus 20 versus 100
      plus minus versus 100 plus minus 20 versus 100 plus minus ms), and His--Purkinje
      (HV) conduction time (40 plus minus 12 versus 40 plus minus 13 versus 40 plus
      minus 12 ms). Ventricular activity duration was 110 plus minus 11 ms at baseline,
      110 plus minus 10 ms after saline infusion (p = NS), and 88 plus minus 13 ms
      after Enalaprilat administration (p < 0.001). Angiotensin-converting enzyme
      inhibition appears to produce significant reduction in ventricular activity
      duration (increase in intraventricular conduction velocity).

PMID- 11835079
TI  - Population Pharmacokinetics of Digoxin in Duchenne Muscular Dystrophy (DMD)
      Patients.
AB  - Routine clinical pharmacokinetic data collected from Duchenne muscular dystrophy
      (DMD) patients receiving digoxin have been analyzed to evaluate the role of
      patients' characteristics for estimating dosing regimens. The data were analyzed
      using NONMEM, a computer program designed for population pharmacokinetic analysis
      that allows pooling of data. The pharmacokinetic model of digoxin was described
      using a one-compartment steady-state model. The effect of factors on digoxin
      clearance was investigated. NONMEM estimates indicate that digoxin clearance was
      influenced by the variables of body weight and combination with diuretics. The
      interindividual variability in digoxin clearance was modeled with proportional
      error with an estimated coefficient of variation of 25%, and the intraindividual
      variability in digoxin concentration was modeled with equal error with an
      estimated standard deviation of 0.0828 ng ml(minus sign1). In order to determine
      whether the population parameters obtained in this study were accurate, we
      administered digoxin according to individual dosage regimens in four DMD
      patients, using these values obtained by the Bayesian method. As a result, we
      found that mean prediction error, which indicates the deviation of prediction
      accuracy for digoxin concentration in plasma, was small, as were mean absolute
      prediction error and root mean squared error, showing the accuracy of this
      prediction method. The dosing method based on clearance values obtained by NONMEM
      analysis allowed the prediction of the steady-state concentration as a function
      of maintenance dose with acceptable error for therapeutic drug monitoring.

PMID- 11835080
TI  - Dose-Related Hepatic Blood Flow Effects Differentiate Nicorandil, Hydralazine,
      and Isosorbide Dinitrate in Healthy Subjects.
AB  - Dose response on hepatic blood flow of nicorandil (2.5, 5, and 10 mg), isosorbide
      dinitrate (5, 15, and 40 mg), and hydralazine (10, 25, and 50 mg) was assessed in
      18 healthy subjects (6 per drug) using a three-period crossover design.
      Indocyanine green clearance was used to estimate hepatic blood flow before and at
      two timepoints after dosing. Greater hepatic blood flow changes occurred 90 (than
      30) min after nicorandil and isosorbide dinitrate, and 60 (than 150) min after
      hydralazine. Nicorandil (mixed vasodilator) decreased hepatic blood flow by minus
      sign13 plus minus 4% (p < 0.05), minus sign15 plus minus 7%, and minus sign21
      plus minus 6% (p < 0.05) (mean plus minus standard error of the mean) after 2.5,
      5, and 10 mg, respectively; blood pressure was not reduced and heart rate was
      unchanged. Individual changes correlated poorly with plasma nicorandil
      concentrations. Isosorbide dinitrate (predominant venodilator) decreased hepatic
      blood flow by minus sign23 plus minus 9%, minus sign27 plus minus 5% (p < 0.05),
      and minus sign26 plus minus 7% (p < 0.05) after 5, 15, and 40 mg, respectively;
      blood pressure decreased (8--12 mm Hg) and heart rate increased (8 beats
      min(minus sign1)). Hydralazine (arterial dilator) increased hepatic blood flow by
      29 plus minus 16%, 32 plus minus 11% (p < 0.05), and 33 plus minus 26% after 10,
      25, and 50 mg, respectively; blood pressure was unchanged and heart rate
      increased (16 beats min(minus sign1)). Hepatic vascular resistance increased
      after nicorandil and isosorbide dinitrate but decreased after hydralazine. As
      assessed by hepatic blood flow response, nicorandil behaves more like a
      predominant venodilator than a direct arterial dilator. Dose and time variables
      were important to understanding the overall hemodynamic profile of each drug.

PMID- 11835081
TI  - Augmented Digoxin Concentrations with Carvedilol Dosing in Mild-Moderate Heart
      Failure.
AB  - Carvedilol is a partially selective beta-adrenergic blocking agent. Recent
      clinical studies have suggested that carvedilol may improve left ventricular
      function and symptoms in patients with heart failure. The effects of carvedilol
      on serum digoxin levels in subjects with heart failure is unknown. Therefore, 22
      New York Heart Association functional class II--III patients with idiopathic
      dilated cardiomyopathy were studied in a prospective, double-blind, placebo
      controlled trial. The patients were selected from a clinical trial evaluating the
      efficacy and hemodynamic effects of chronic carvedilol treatment in heart
      failure. Carvedilol administration was associated with a 26% increase in steady
      state serum digoxin concentrations versus placebo (p = NS). No patients required
      digoxin dosage adjustments and there were no clinically significant adverse
      events directly attributable to an increase of serum digoxin concentration. Thus,
      clinical significant changes in serum digoxin concentrations are not observed in
      most patients who receive carvedilol. However, the small increase in serum
      digoxin concentrations warrants caution be exercised in patients with elevated
      digoxin concentrations during coadministration of carvedilol.

PMID- 11835082
TI  - Disposition of Misoprostol and Its Active Metabolite in Impaired Hepatic
      Function.
AB  - The pharmacokinetics of misoprostol and its active metabolite, misoprostol acid,
      was assessed in 17 healthy subjects and 17 subjects with various degrees of
      hepatic impairment. Before misoprostol administration, subjects underwent
      antipyrine and indocyanine green clearance studies to assess hepatic functional
      capacity. Subjects were administered 400 mcg of oral misoprostol in an open-label
      design. There was a lower antipyrine clearance in the group with hepatic disease
      as compared to normal volunteers (0.56 versus 0.80 ml min(minus sign1) kg(minus
      sign1), respectively, p = 0.022). There was no difference in indocyanine green
      clearance values between groups. The C(max), t(1/2)&bgr, and &lsqb;Formula: see
      text] tended to be larger in the hepatic group; however, there was no statistical
      difference. Adverse events, mostly gastrointestinal in nature, occurred more
      often in the subjects with hepatic disease. These data suggest the
      pharmacokinetics of misoprostol may be altered in the presence of hepatic
      disease. However, because of significant interpatient variability, definitive
      dosing recommendations cannot be made. Further study in this area is needed.

PMID- 11835083
TI  - Editorial: Therapeutics, Clinical Phamacology, Molecular Pharmacology: Have We
      Lost Our Academic Way?

PMID- 11835084
TI  - Will the Nineties Be the Decade We Lost the Battle Against Drug-Resistant
      Microbes?
AB  - Antimicrobial resistance is reaching epidemic proportions. Bacteria have
      developed an impressive array of defenses to protect themselves against potent
      compounds. The widespread emergence of resistance has complicated the treatment
      of infections due to Staphylococcus, Streptococcus, Enterococcus, Neisseria,
      Haemophilus, gram-negative enteric bacilli, and Pseudomonas. Multidrug-resistant
      tuberculosis poses a grave public health problem, particularly among the homeless
      and those infected with HIV. HIV resistance to nucleoside analogs such as
      zidovudine is increasingly common and seriously threatens their clinical
      usefulness. It is apparent that simply producing new drugs is not a viable
      solution to the resistance crisis. Rational use of existing antimicrobial agents
      is vital, and combination regimens must be intelligently deployed. State-of-the
      art molecular epidemiology will aid in the detection, analysis, and termination
      of resistance epidemics. Control of drug-resistant Mycobacterium tuberculosis
      will require appropriate initial treatment regimens, proper therapeutic
      modification using the latest susceptibility testing methods, and strong emphasis
      on measures ensuring compliance. HIV resistance is a challenging problem, and
      novel strategies will be necessary to combat it. Recognition that drug resistance
      among bacteria and viruses is a rapidly growing threat worldwide is an important
      first step toward finding effective long-term solutions.

PMID- 11835085
TI  - A Primary Care Clinician's and Consultant's Guide to Medicating for Pain and
      Anxiety Associated with Outpatient Procedures.
AB  - This article offers clinical suggestions for the design of a patient-specific
      outpatient treatment plan for managing and reducing short-term pain associated
      with outpatient procedures. These procedures may actually produce pain, or they
      may be perceived as causing pain and anxiety. The article will also focus on the
      design of a patient-specific outpatient treatment plan for managing and reducing
      short-term procedural-induced anxiety, as perceived pain and anxiety or pain and
      anxiety themselves may be a reason for which patients are noncompliant with their
      office visits. The treatment plan will focus on pre-procedure, peri-procedure,
      and post-procedure interventions using nonsteroidal anti-inflammatory drugs and
      anxiolytics (benzodiazepines, opiate agonists, and sedative hypnotics). The plan
      also includes adjuvant therapy to decrease the patient's perception of pain,
      anxiety, fear of procedure, and fear of outcomes in order to facilitate a higher
      degree of compliance with office procedures. This article also accounts for the
      patient's physiology, pathophysiology, pathology, and iatrogenic effects from
      drug treatment plans.

PMID- 11835086
TI  - Ramipril Enhances Autonomic Control in Essential Hypertension: A Study Employing
      Spectral Analysis of Heart Rate Variation.
AB  - We estimated the effect of an angiotensin-converting enzyme inhibitor, ramipril,
      on the sympathetic and parasympathetic input to the sinoatrial node of
      hypertensive patients using spectral and time domain analysis of heart rate
      variation (HRV). The heart rate of patients with essential hypertension was
      recorded during spontaneous breathing at rest and during controlled deep
      breathing. The periodic HRV was quantified at low-frequency (0.025--0.075 Hz),
      mid-frequency (0.075--0.125 Hz) and high-frequency (0.15--0.40 Hz) bands.
      Ramipril changed the balance of autonomic nervous system assessed by spectra: the
      parasympathetic tone increased (p < 0.05) and the sympathetic tone decreased (p <
      0.01). There was an inverse correlation between the decrease in diastolic blood
      pressure and increase in the mid-frequency HRV, which is connoted with resetting
      of the baroreceptor reflex by ramipril. Thus, ramipril treatment was associated
      with improved autonomic control of the circulatory system.

PMID- 11835087
TI  - Effects of the Calcium Antagonist Felodipine on Resting and Stress Testing Blood
      Pressure in Essential Hypertension.
AB  - The current study analyzed the effects of different doses of the calcium channel
      blocker felodipine on cardiovascular response to a set of standardized laboratory
      tasks. We randomly allocated 21 essential hypertensive patients to receive
      extended release felodipine 5 mg, felodipine 10 mg and placebo, each given once
      daily for 2 weeks, according to a double-blind 3-period design. At the end of
      each treatment period, patients were examined at resting baseline and while
      performing a mental arithmetic test, a handgrip test and a cycle ergometry test.
      Compared to placebo, the average fall in resting blood pressure (BP) was of 7.9
      +/- 5.6/6.1 +/- 4.5 mm Hg with felodipine 5 mg (p < 0.01) and of 15.1 +/-
      5.8/13.9 +/- 4.5 mm Hg with felodipine 10 mg (p < 0.001). During mental
      arithmetic, BP decrease was 11.6 +/- 8.1/9 +/- 5 mm Hg with felodipine 5 mg (p <
      0.01) and 20.4 +/- 8.1/15.3 +/- 5 mm Hg with felodipine 10 mg (p < 0.001). During
      handgrip test, BP was significantly reduced after both felodipine doses by 11.7
      +/- 9.3/9.5 +/- 6.5 mm Hg (p < 0.05) and 22.1 +/- 9.3/22.4 +/- 6.5 mm Hg (p <
      0.001), respectively. During cycle ergometry, systolic BP was significantly
      reduced after felodipine 10 mg by 20.1 +/- 9.4 mm Hg (p < 0.001), whereas the
      fall induced by felodipine 5 mg (7.7 +/- 9.4 mm Hg) was not statistically
      significant (p > 0.05); diastolic BP was significantly reduced by both felodipine
      doses [average fall of 6.6 +/- 5.8 mm Hg (p < 0.05) after felodipine 5 mg and of
      12.7 +/- 5.8 mm Hg (p < 0.001) after felodipine 10 mg]. There was no treatment
      effect on the magnitude of systolic BP reactivity from baseline during either
      mental arithmetic, handgrip test or cycle ergometry (all, p > 0.05). Heart rate
      values were significantly higher after both felodipine doses than after placebo,
      either at rest or during stress testing (all, p < 0.05). These data suggest that
      felodipine, especially at higher doses, may be effective in lowering BP not only
      at rest but also during exposure to commonly recurring stressful situations.

PMID- 11835088
TI  - The Dose--Plasma Concentration Relationship of Tranexamic Acid during Surgery.
AB  - Plasma specimens from 59 patients undergoing cardiac operations utilizing
      extracorporeal circulation underwent determination of tranexamic acid
      concentration to explore the effect of dose administered to plasma concentration.
      Each patient received one of five doses of tranexamic acid in double-blinded,
      randomized fashion, ranging from 2.5 to 40 mg kg(minus sign1) for the loading
      dose and from 0.25 to 4.0 mg kg(minus sign1) h(minus sign1) for a subsequent
      infusion. Plasma collections occurred after completion of the loading dose,
      during extracorporeal circulation, before protamine infusion, after protamine
      infusion, and following arrival in the intensive care unit. The samples were
      analyzed using high-performance liquid chromatography. The logarithm of plasma
      concentration varied linearly with the logarithm of dose administered at each
      sampling time (r(2) values 0.82, 0.95, 0.89, 0.74 and 0.93 for the respective
      collection times). Plasma concentrations did not decrease during extracorporeal
      circulation despite absence of tranexamic acid in the pump prime. However,
      concentrations varied inexplicably following protamine administration and
      decreased in the intensive care unit.

PMID- 11835089
TI  - Dose-Related Hemodynamic Effects of Enalaprilat in Patients with Ischemic Heart
      Disease.
AB  - To investigate the dose-related hemodynamic effects of angiotensin-converting
      enzyme inhibition (ACEI) in patients with angina pectoris (AP), five patients
      underwent right and left heart catheterization, and left ventriculogram before
      and 10 min after administration of 1.25 mg enalaprilat intravenously (Group 1).
      The results were compared with those of five patients with similar
      characteristics who received 2.5 enalaprilat (Group 2). There were no baseline
      differences between groups. After enalaprilat administration, there was
      significant differences between Groups 1 and 2, as follows: systolic blood
      pressure was 138 plus minus 16 versus 127 plus minus 14 mmHg (p = 0.05), left
      ventricular end-diastolic pressure was 15 plus minus 6 versus 7 plus minus 4 mmHg
      (p = 0.04), systemic vascular resistance was 1341 plus minus 290 versus 965 plus
      minus 271 dyne/sec/cm(minus sign5) (p = 0.05), pulmonary vascular resistance was
      174 plus minus 39 versus 156 plus minus 15 dyne/sec/cm(minus sign5) (p = 0.05),
      end-diastolic volume was 87 plus minus 34 versus 107 plus minus 17 ml (p = 0.03),
      cardiac index was 3.0 versus 4.5 L min(minus sign1) m(minus sign2) (p = 0.01),
      left ventricle end-systolic wall stress was 31 plus minus 10 versus 22 plus minus
      9 k dyne cm(minus sign5) (p = 0.01), ejection fraction was 69 plus minus 12
      versus 81 plus minus 8% (p = 0.01), and wall motion index was 1.14 plus minus 0.1
      versus 1.02 plus minus 0.1 (p = 0.001). These results indicate that enalaprilat
      has dose-related effects improving hemodynamics and ventricular function in
      patient with AP.

PMID- 11835090
TI  - Pharmacokinetics of a New Anticonvulsant (CGP 33101) in Epileptic Male Patients
      and Healthy Male Subjects after Single Ascending Oral Doses of 400--1200 mg.
AB  - Information on the pharmacokinetic behavior of a new anticonvulsant agent (CGP
      33101) was obtained after oral administration of ascending doses to male
      epileptic patients maintained on existing antiepileptic drug (AED) therapy, as
      well as to healthy male subjects. Single doses of 400, 800 and 1200 mg were
      administered to 12 of the 16 epileptic patients participating in the clinical
      trial and all 3 healthy subjects; the remaining patients received placebo doses
      on each dosing occasion. The study's primary objectives were to obtain single
      dose add-on tolerability information, as well as preliminary pharmacokinetic data
      for the drug candidate. Either placebo or 400, 800 and 1200 mg of the compound,
      administered as 200-mg tablets, were coadministered with enzyme-inducing
      antiepileptic medications to the patients participating in the trial. These AEDs
      dilantin, tegretol, depakote, mysoline and tranxene) were administered
      individually or as combination therapy of two or three, with each patient being
      on the existing therapy for a minimum of 3 weeks prior to receiving the drug
      candidate (CGP 33101) as an add-on. Three healthy male subjects were included in
      the study to provide concurrent pharmacokinetic data at equivalent doses, as well
      as additional safety data in the absence of concomitant medication. Plasma
      concentrations of the new drug candidate were determined in samples obtained
      predose through 120-h postdose, with a 5-day washout period between doses.
      Preliminary pharmacokinetic parameters, such as peak plasma concentrations
      (C(max), times to peak levels (T(max)), areas under the plasma concentration-time
      curve (AUC) and terminal half-lives (T(1/2)), were determined in both epileptic
      patients and healthy subjects following all three doses. The mean T(max) values
      were similar for all three dose levels in both patients and subjects, indicating
      that the rate of absorption was comparable. Mean C(max) values increased in a
      dose-related manner with increasing dose in epileptic patients. The corresponding
      values showed a dose-proportional relationship in healthy subjects. The
      relationship between C(max) values and the administered dose did not change in
      patients or subjects when the data was corrected for dose and/or body weight.
      After the peak, plasma levels declined, but were still quantifiable in most
      patients and subjects at 36 h following all three doses. The mean AUC values
      increased in a dose-proportional manner with increasing dose in healthy subjects.
      The corresponding mean patient data appeared to increase in a dose-related
      manner. The relationship between AUC values and size of the administered dose did
      not change in either patients or subjects when the data was corrected for dose
      and/or body weight. The terminal elimination half-lives (T(1/2)) were apparently
      shorter in patients compared to the healthy subjects and were independent of the
      close administered.

PMID- 11835091
TI  - A Single-Dose Bioavailability Study of Pamidronate Disodium after Oral
      Administration as Encapsulated Enteric-Coated Pellets, Enteric-Coated Tablets,
      and a Solution to Patients with Postmenopausal Osteoporosis.
AB  - This was a pilot, single-center, single-dose, open-label, randomized three-way
      crossover study comparing the relative bioavailability of pamidronate disodium
      after oral doses of the drug administered as four capsules, each containing 75 mg
      enteric-coated pellets, two 150-mg enteric-coated tablets and 300 mg in solution
      (reference standard) in patients with postmenopausal osteoporosis. Results from
      seven patients are reported; five subjects completed all three phases of the
      study---one received solution and pellets, and another one received pellets and
      tablets. The onset of urinary excretion (an indicator of relative onset of oral
      absorption) of pamidronate disodium occurred in the first 2 h in all (except one)
      patients for solution and pellets, whereas the onset of urinary excretion for the
      tablets was prolonged and more variable. The extent of absorption was estimated
      in terms of percent of administered dose excreted in urine up to 72 h after
      dosing. The extend of absorption was highest after the pellets (mean plus minus
      S.D., 0.37 plus minus 0.27%), followed by the solution (0.20 plus minus 0.16%).
      The extent of absorption after the tablets (0.09 plus minus 0.10%) was the lowest
      and most variable. The poorer and more variable bioavailability of the tablets
      may be explained by the longer and more variable residence time of the tablets in
      the stomach.

PMID- 11835092
TI  - Pharmacokinetics of Pamidronate Disodium in Cancer Patients after a Single
      Intravenous Infusion of 30-, 60- or 90-mg Dose over 4 or 24 Hours.
AB  - The objective of this study was to determine the pharmacokinetics of pamidronate
      disodium in plasma and urine after a single intravenous infusion of the drug to
      cancer patients at risk for developing bone metastases. Thirty-six patients were
      randomized into six treatment groups to receive 30-, 60- or 90-mg doses of the
      drug by 4- or 24-h intravenous infusions. Plasma and urine samples were collected
      at intervals for up to 144 h after drug administration and were assayed for
      pamidronate disodium using validated reversed-phase HPLC methods. The percentage
      of the administered dose excreted in urine following a 4- or 24-h infusion of 30
      , 60- or 90-mg pamidronate disodium ranged from 30% to 60% except for one
      individual who excreted 96% by this route of elimination. There was a linear
      relationship between amount of drug excreted in urine and dose. Curve fitting of
      ARE (amount of drug to be excreted in urine) data indicated that the disposition
      kinetics of the drug was consistent with a biexponential process with overall
      mean plus minus S.D. half-life values of 2.1 plus minus 1.8 and 26.9 plus minus
      8.7 h for the alpha and beta phases, respectively. The results of this study
      showed that the drug exhibited dose proportionality in its pharmacokinetic
      behavior over the 30--90-mg range regardless of whether it was infused over a 4-
      or 24-h interval.

PMID- 11835094
TI  - Clinical Therapeutic Conference: Vancomycin Nephrotoxicity.

PMID- 11835093
TI  - Androgenic Activity of Antiandrogens Predicted by Fit into DNA.
AB  - Computer modeling including graphics and energy calculations were employed for
      the first time to examine the stereochemical fit of antiandrogens into double
      stranded DNA. In this study, we assessed the relative fit of antiandrogens in the
      cavity between base pairs known to accommodate androgens. When compared to
      testosterone which was given a normalized value of 100%, the antiandrogens
      manifested the following order of fit: RU23908 (88%) > hydroxyflutamide (71%) >
      cyproterone acetate (41%). A correlation was observed between the relative fit of
      the antiandrogens and reported agonistic properties as assessed by the ability to
      increase nuclear androgen receptor levels in the rat ventral prostate. These
      findings may be useful in the design and development of androgen antagonists
      without agonistic activity.

PMID- 11835095
TI  - Editorial: The Basis of Pharmaceutical Approval.

PMID- 11835096
TI  - Antipyrine Metabolism during Chemotherapy with 5-Fluorouracil Plus Folinic Acid
      in Patients with Liver Metastases from Primary Colorectal Cancer.
AB  - Current evidence suggests that the drug-metabolizing capacity of the liver can be
      altered by neoplastic lesions and by the chemotherapeutic agents used to treat
      them. Antipyrine metabolism is a widely used dynamic test for assessing mixed
      hepatic oxidase system activity in humans. This study was conducted to determine
      the effects of 5-fluorouracil-folinic acid chemotherapy on hepatic drug
      metabolization in patients with diffuse liver metastases from colorectal tumors
      using antipyrine metabolism as an index. Twenty-three patients, all with diffuse
      liver metastases from primary colorectal tumors and normal liver function tests,
      were treated with 5-day cycles of 5-fluorouracil (5-FU) (370 mg m(minus sign2)
      day(minus sign1) I.V.) and folinic acid (200 mg m(minus sign2) day(minus sign1)
      I.V.) administered every 28 days. Antipyrine metabolism was assessed before
      initiation of therapy and after each 5-day cycle to determine the effects of this
      chemotherapeutic protocol on the mixed-hepatic oxidase system. Response to
      treatment was assessed after 4 months. None of the patients displayed any change
      in antipyrine metabolism following treatment. There was no correlation between
      the ability to metabolize antipyrine and the response to chemotherapy. 5FU has
      been found to decrease antipyrine metabolism in rats with no liver disease. The
      absence of such an effect in our patients is thought to be due to inductive
      effects exerted by the metastases on the mixed hepatic oxidase system and
      modification of 5-FU metabolism by folinic acid. The liver appears to have an
      enormous functional reserve, even when there is massive tumor involvement.

PMID- 11835097
TI  - A Study Design for Comparing the Effects of Missing Daily Doses of
      Antihypertensive Drugs.
AB  - In this double-blind, 6-week study comparing once-daily oral betaxolol and
      atenolol, the study design allowed the effects of simulated drug noncompliance to
      be examined. Overall similar blood pressure and heart rate responses were seen in
      114 patients with mild-to-moderate hypertension. Similarly, there was no
      statistically significant difference in percentage of patients achieving goal
      diastolic blood pressure reductions at the end of 6 weeks of active therapy
      (betaxolol, 87%, 46/53; atenolol, 82%, 44/54), and safety results overall were
      similar. However, when patients randomly received placebo for two consecutive
      treatment days in either the fifth or sixth week of the study to simulate the
      effect of missing doses, magnitude and duration of effect on systolic blood
      pressure (p = 0.006), diastolic blood pressure (p = 0.02) and heart rate (p =
      0.001) were significantly greater for betaxolol than atenolol as calculated from
      28-h ambulatory blood pressure monitoring data. Although betaxolol and atenolol
      monotherapy are equally effective in controlling blood pressure when taken
      consistently, the blood pressure and heart rate response with betaxolol is
      significantly superior for at least 24 h after missing a dose, an important
      consideration related to patient noncompliance. These results are compatible with
      the different elimination half-lives of each drug.

PMID- 11835098
TI  - Is the Degree of Arrhythmia Suppression a Predictor of Survival?
AB  - The effectiveness of an antiarrhythmic drug is judged by the degree of
      ventricular arrhythmia suppressed by the drug. It has been suggested that a
      certain degree of ventricular arrhythmia suppression should be targeted to prove
      efficacy. Targets used to define the effectiveness of an antiarrhythmic agent
      included an 80% reduction in the ventricular premature complexes (VPCs) and 90%
      suppression of nonsustained ventricular tachycardia (NVT) episodes or complete
      abolition of runs of sustained VT (SVT) [1]. Other dose-adjusted antiarrhythmic
      trials have attempted to achieve either isolated control of the PVCs of greater
      than-or-equal70% [2--5] with the suppression of the high grades of arrhythmia
      such as couplets and NVT of >90% and 100%, respectively [2, 3]. Such targets of
      arrhythmia suppression were recommended to avoid errors encountered with the
      occurrence of the spontaneous variability of ventricular arrhythmia and to be
      confident that antiarrhythmic therapy has produced a true drug effect [6].
      Presently, there is no evidence that suppression of these arrhythmias with type I
      antiarrhythmic drugs is likely to reduce sudden death [4, 6]. The survival of
      patients with frequent VPCs and high-grade forms (couplets [C], NVT) and organic
      heart disease is not dependent on the degree of arrhythmia suppression. The
      survival of patients with low LVEF of <40% and runs of NVT is improved and is
      similar to that of patients with good LVEF of greater-than-or-equal40%. Such a
      lack of correlation between arrhythmia suppression and survival might be a unique
      feature of the antifibrillatory drugs and might not be applied to the antiectopic
      drugs. If a high degree of arrhythmia suppression is not needed, lower targets of
      suppression may be necessary. Lower drug dosages may improve the risk--benefit
      ratio of antiarrhythmic treatment.

PMID- 11835099
TI  - Effect of Calcium Entry Blocking Agents (Nifedipine and Verapamil) on Myocardial
      Recovery during Reperfusion.
AB  - A comparative study on isolated guinea pig hearts was carried out to determine
      the effect of calcium entry blocking agents: nifedipine- and verapamil-added
      reperfusion solutions on myocardial recovery after global ischemia. After 20 min
      of normothermic ischemia, three groups of solutions were used for reperfusion (10
      animals each): (1) Nifedipine-added (10--8 mmol L(minus sign1)) Krebs--Henseleit
      solution; (2) verapamil-added (10--8 mmol L(minus sign)) Krebs-Henseleit
      solution; (3) Krebs--Henseleit solution. Postischemic myocardial functions
      (ventricular contractile force and heart work) and enzyme activities were
      compared with their preischemic values. The addition of calcium entry blocking
      agents does not have any significant advantage over control solutions in
      myocardial recovery.

PMID- 11835100
TI  - Efficacy and Safety of Bepridil in Chronic Stable Angina Pectoris Refractory to
      Nifedipine.
AB  - The efficacy and safety of bepridil in chronic stable angina pectoris refractory
      to an extended-release preparation of nifedipine were evaluated in this open
      label prospective study. Patients whose angina had not responded adequately to
      maximum tolerated doses of nifedipine received bepridil for 8 weeks after a 2
      week baseline period at their established dose of nifedipine. Twenty-five
      patients entered the bepridil treatment period. Total exercise time (mean plus
      minus SD) was significantly increased at the end of bepridil therapy (9.3 plus
      minus 2.3 min) compared with the end of nifedipine baseline period (8.40 plus
      minus 2.3 min, p = 0.02). Time to the onset of angina increased from 6.1 plus
      minus 2.7 min to 8.1 plus minus 2.3 min, p < 0.01. Time to 1-mm ST depression
      increased from 7.0 plus minus 2.7 min to 8.4 plus minus 2.3 min, p < 0.01.
      Nitroglycerin consumption decreased from 3.01 plus minus 5.6 to 0.56 plus minus
      1.3 tablets week(minus sign1), p < 0.05. The mean weekly angina attack rate
      decreased from 4.34 plus minus 5.3 to 1.33 plus minus 2.2, p < 0.01. Therapy with
      bepridil resulted in few adverse experiences. The mean QT(c) interval was
      significantly prolonged from 0.40 + 0.03 s at baseline to 0.45 + 0.045 s at the
      end of bepridil therapy (p < 0.001). There were no serious adverse events. The
      results of this study indicated that bepridil provides effective and safe
      treatment of stable angina pectoris in patients whose angina is not adequately
      controlled by nifedipine.

PMID- 11835101
TI  - Continuous Infusion Ranitidine in Postoperative Pediatric Liver Transplant
      Patients: Effects on Intragastric pH, Gastrointestinal Bleeding and Metabolic
      Alkalosis.
AB  - The effects of ranitidine, an H(2)-receptor antagonist, on gastric pH, incidence
      of upper gastrointestinal hemorrhage and postoperative metabolic alkalosis were
      evaluated in 23 pediatric liver transplant recipients. Intragastric pH probes
      were inserted postoperatively and pH was monitored for 48 h. Ranitidine was
      infused for 48 h at 0.2 mg kg(minus sign1) h(minus sign1) (0.15 with renal
      impairment) and increased once by 0.05 mg kg(minus sign1) if the pH was less than
      4.0 for 4 h. The pretreatment gastric pH was 2.1 plus minus 0.7; ranitidine
      infusion raised the pH to 6.8 plus minus 0.6 (p greater-than-or-equal 0.05). An
      intragastric pH > 4 was achieved in 64 plus minus 36 min, with a median ED(50)
      (50% of maximum response) of 0.24 mg kg(minus sign1). The pH was < 4 for 5.3 plus
      minus 4.8% of the time after the initial response. Loss of pH control occurred in
      three patients, two of whom had bacterial sepsis. The incidence of upper
      gastrointestinal bleeding and metabolic alkalosis was evaluated by comparing the
      study patients to age- and weight-matched historic controls from our center.
      Bleeding occurred in 1 of 23 (4%) study patients compared to 7 of 23 (30%)
      controls (p greater-than-or-equal 0.05). Metabolic alkalosis did not develop in
      the study patients at 24 or 48 h postoperatively (p greater-than-or-equal 0.05
      versus controls). Whole blood cyclosporine levels and hepatocellular enzymes were
      similar in the two groups. We conclude that continuous intravenous infusion of
      ranitidine in the postoperative pediatric liver transplant recipient raises
      intragastric pH, decreases the incidence of upper gastrointestinal hemorrhage and
      prevents the development of metabolic alkalosis.

PMID- 11835102
TI  - Erythromycin in the Treatment of Diabetic Gastroparesis.
AB  - The macrolide antibiotic erythromycin has been known to be associated with
      increased gastrointestinal motility since its introduction more than 35 years
      ago. Investigators have, thus, sought to take advantage of this side effect in
      patients with gastric stasis secondary to long-standing insulin-dependent
      diabetes mellitus (IDDM). The hormone motilin induces phase 3 contractions of the
      migrating motor complex (MMC) to induce peristalsis and facilitate gastric
      emptying in normal subjects. Patients with diabetic gastroparesis lack adequate
      phase 3 activity to effectively empty gastric contents. Exogenous motilin
      administered to animals and patients with diabetic gastroparesis has proven
      useful for promoting gastric emptying. However, motilin is expensive to produce
      and must be given intravenously. Erythromycin has been shown to induce premature
      phase 3 activity via stimulation of motilin receptors, so investigators evaluated
      its efficacy for the treatment of diabetic gastroparesis. Early studies in
      animals with experimental gastroparesis indicated that erythromycin may be a
      useful prokinetic agent. Human studies of both intravenous erythromycin and
      chronic oral erythromycin in patients with diabetic gastroparesis resistant to
      other prokinetic agents showed that gastric retention was indeed reduced and
      symptomatic improvement achieved. Even though erythromycin lost some of its
      prokinetic activity with chronic oral dosing, gastric retention was still
      significantly reduced compared to placebo or baseline. Although prokinetic agents
      like metoclopramide, domperidone and cisapride are effective for the treatment of
      patients with diabetic gastroparesis, tachyphylaxis and adverse effects are
      obstacles to their use. Erythromycin appears to be both effective and well
      tolerated in clinical studies. At this time it should be reserved for the
      treatment of patients with diabetic gastroparesis who are resistant to or
      intolerant of other prokinetic agents. Future research on erythromycin's long
      term safety and comparative efficacy will further define its role.

PMID- 11835103
TI  - Human Pharmacokinetics of the Neuroprotective Agent NBQX.
AB  - We studied the pharmacokinetics of the glutamate antagonist NBQX (6-nitro-7
      sulphamoylbenzo[f]quinoxaline-2,3-dione) in 16 normal male volunteers aged 18--37
      years in a double-blind, placebo-controlled design. Intravenous infusions of
      0.0075 and 0.03 mg kg(minus sign1) over 30 min were given to six subjects at each
      dose level (parallel groups). Two subjects at each dose level received placebo.
      The drug was well tolerated and no clinically significant alterations of
      cardivascular or renal function or in biochemical and hematological parameters
      were observed. Mean values of C(max) were 41 and 177 ng ml(minus sign1) at the
      two-dose levels. Compartmental pharmacokinetic analysis yielded a plasma half
      life of 0.75 h, a total plasma clearance of 0.222 L h(minus sign1) kg(minus
      sign1) and a volume of distribution at steady state of 0.153 L kg(minus sign1).
      The renal clearance was 0.130 L h(minus sign1) kg(minus sign1) implying tubular
      secretion of the drug.

PMID- 11835104
TI  - Effect of Single Dose Fluoxetine on Theophylline Serum Concentrations.
AB  - Fluoxetine has been previously reported to elevate plasma concentrations of
      several hepatically metabolized medications. Eight healthy male volunteers
      received intravenous aminophylline (approximately 6 mg kg(minus sign1)) on two
      occasions separated by 2 weeks. A 40-mg dose of oral fluoxetine was administered
      8 h prior to the second administration of fluoxetine. Blood samples were
      collected and assayed for theophylline. Fluoxetine administration was not
      associated with any significant differences with respect to peak theophylline
      serum concentration, total body clearance, or half-life. Possible explanations
      include the fact that only a single dose of fluoxetine was administered and low
      fluoxetine serum concentrations were present at the time of aminophylline
      administration. The most likely explanation, however, is the fact that fluoxetine
      inhibits cytochrome P450 2D6 activity, whereas theophylline is predominately
      metabolized by cytochrome P450 1A2. In summary, a single 40-mg dose of fluoxetine
      failed to alter the plasma concentrations of theophylline when administered
      intravenously as aminophylline.

PMID- 11835106
TI  - Noncardiac Chest Pain: A Focus on Psychogenic Causes.
AB  - Patients presenting with noncardiac chest pain of psychogenic origin are one of
      the more challenging clinical dilemmas to primary care medicine. Key aspects to
      recognition of these patients are predominance of autonomic complaints, multiple
      presentations, clustering of physical complaints and a repeated history of
      negative cardiac pathology, a clinical profile of anxiety or panic disorder.
      Therapy can be achieved by the use of benzodiazepines. Psychiatric consultation
      is to be sought following successful symptom abatement from a parenteral
      benzodiazepine challenge in the emergency department on successive occasions.

PMID- 11835105
TI  - Evaluation and Management of Sickle Cell Disease in the Emergency Department (An
      18-year Experience): 1974--1992.
AB  - Painful episodes are the most frequent complaints of patients with sickle cell
      disease. The Emergency Department (ED) has provided management for acute events
      using the usual triage format for emergencies. A prospective study evaluated the
      role of the ED in the care of adults with sickle cell disease (SCD). The
      protocol, thus, addressed issues of acute events related to SCD and provided
      better care for patients with SCD in the ED. Approximately 37% of ED visits were
      for painful events. An inciting cause was identified in 35% of painful events and
      75% of these required admission to the hospital. A 15-year follow-up
      prospectively showed similar results and that uncomplicated pain crisis can be
      treated with ED protocols. Outpatient clinics and urgent centers could reduce
      these visits. Absolute indications for admission include sepsis, fever >102
      degreeF, white cell counts >20 000, worsening anemia, hypoxemia, acute chest
      syndrome and new CNS events. Patient database in the ED must be revised annually
      to avoid extensive workup in the ED and a complete history/physical examination,
      and a CBC could be sufficient for triage in an uncomplicated pain crisis. An
      acceptable protocol for care should be available at all EDs and a registry and
      information system for SCD will discourage overutilization of investigational
      tests and visits to multiple EDs.

PMID- 11835107
TI  - Fundamental Issues of Choosing the Right Type of Trial.
AB  - BACKGROUND: Relevant advantages and disadvantages of crossover/self-controlled
      and parallel group studies are discussed. RESULTS: For ethicists crossovers are
      frequently less of a problem. Also, they may be less costly, and, in addition,
      statistically more powerful. If the treatments in a trial are curative, however,
      or if the variables are subjective, a parallel group design is the right type of
      trial. In case of unstable disease, or a negative correlation in a treatment
      comparison, this is so. CONCLUSIONS: Routinely including a set of rules prevents
      procedural biases and wrong study designs. The present paper is a preliminary
      effort for the very purpose of that.

PMID- 11835108
TI  - Clinical Therapeutic Conference.

PMID- 11835109
TI  - When and how to assess quality of life in chronic lung disease.
AB  - Since the early 1980s there has been increasing awareness of the importance of
      quantifying health-related quality of life (HRQL) in patients with chronic
      respiratory disorders included in clinical trials. HRQL scores are clearly
      complementary to functional assessments, and have been shown to be better
      predictors of use of health resources (hospital readmissions, GP consultations
      exacerbations) than pulmonary function tests alone. Two types of HRQL score are
      available: "generic scores" cover a wide array of items and allow comparison of
      patients suffering from various medical conditions; they may however lack
      responsiveness and therefore underestimate changes in HRQL induced by a
      pharmacological or non-pharmacological management; "disease-specific scores" are
      more responsive and sensitive to changes, and thus more suitable for assessing
      the impact of management on HRQL. The choice of a HRQL instrument must take into
      account its validity, reliability, and responsiveness in the population studied;
      it must also be adapted to the severity of respiratory impairment, to ensure
      optimal discriminant potency. In clinical trials, the use of a "generic" score
      combined with a "disease-specific" score is recommended for optimum assessment.
      This is however too time-consuming for clinical practice: the use of short-time
      HRQL tools quantifying specific items such as resting and exertional dyspnoea,
      activities of daily life and emotional status appears more appropriate in this
      setting; furthermore, these items correlate better with HRQL scores than
      pulmonary function tests.

PMID- 11835110
TI  - Evidence for age-based rationing in a Swiss university hospital.
AB  - AIM: To test the hypothesis that rationing of medical management mainly based on
      age exists in our health care system today. METHODS: We studied 303 consecutive
      patients hospitalised for acute coronary syndrome (ACS) and 163 consecutive
      patients hospitalised with congestive heart failure (CHF). They were divided into
      two age groups; patients aged less than 75 years and those equal to or older than
      75 years. RESULTS: Our main findings were a significant underuse of stress tests
      (p < 0.001) and coronary angiography (p < 0.0001) in elderly patients with ACS
      and a significant underuse of echocardiography (p < 0.0001) in patients with CHF
      of the same age group. In patients with ACS, there was also a trend towards
      underuse of statins in elderly patients with hypercholesterolaemia. In addition,
      we noted that the use of beta-blockers in ACS and of ACE inhibitors in CHF was
      better than in previous published studies but that many patients were still not
      treated according to evidence based medicine. CONCLUSION: The lower rates of
      diagnostic tests performed and the lower statin use observed in elderly patients
      suggest "hidden" rationing of health care in elderly patients.

PMID- 11835111
TI  - Sodium balance-neutral sodium profiling does not improve dialysis tolerance.
AB  - BACKGROUND: Modern haemodialysis monitors offer computerised ultrafiltration and
      sodium concentration profiles which promise better dialysis tolerance. This
      presumption was tested in chronic haemodialysis patients. METHODS: Using
      Fresenius MC 4008S monitors a group of nine patients were dialysed with a given
      ultrafiltration profile comparing sessions with decreasing sodium concentration
      (145 to 133 mmol/L) to sessions with constant sodium concentration (138 mmol/L)
      in random order. The built-in blood volume monitor recorded changes in
      haematocrit and blood volume during each dialysis. The analyses included dialytic
      weight loss, interdialytic weight gain and adverse symptoms (hypotensive episodes
      and muscle cramps). RESULTS: 321 dialysis sessions, 160 with and 161 without
      sodium profile, were available for analysis. No significant differences could be
      detected regarding changes in haematocrit, blood volume and weight in relation to
      sodium profiling. No significant difference in the incidence of hypotension or
      muscle cramping was observed with 55 symptomatic dialyses of 160 with sodium
      profile, compared to 52 symptomatic dialyses of 161 without sodium profile.
      Interdialytic weight gain and consequent weight loss during dialysis was higher
      in symptomatic dialyses both with sodium profile or without sodium profile. The
      same was true of increase in haematocrit and decrease in blood volume, which were
      greater for symptomatic versus symptom-free dialyses irrespective of sodium
      profiling. CONCLUSIONS: Sodium balance-neutral sodium profiling failed to improve
      dialysis tolerance in a group of stable chronic haemodialysis patients. This may
      be explained by the fact that vascular refilling as deduced from changes in
      haematocrit was uninfluenced by sodium profiling.

PMID- 11835112
TI  - Successful diffusible brachytherapy (dBT) of a progressive low-grade astrocytoma
      using the locally injected peptidic vector and somatostatin analogue [90Y]-DOTA0
      D-Phe1-Tyr3-octreotide (DOTATOC).
AB  - We present the therapeutic effect of diffusible brachytherapy (dBT), an
      innovative approach for the management of symptomatic low grade gliomas [1]. This
      protocol uses a radiolabelled small diffusible peptidic vector which is a
      somatostatin analogue to target somatostatin type 2 (sst-2) receptors. The stable
      radioconjugate [90Y]-DOTA0-D-Phe1-Tyr3-octreotide (DOTATOC) is repeatedly
      injected via catheters placed into the resection cavity or into tumour nodules.
      We report on the four year follow-up after initiation of dBT to treat progressive
      disease in a patient with a complex eleven year history of fibrillary low-grade
      astrocytoma. The radiopharmakon was not only locally injected into the resection
      cavity following debulking surgery, but also administered by slow infusion
      technique to target recurrent and infiltrative tumour zones in the subventricular
      region around the inferior and posterior horns. In conclusion, peptidic vector
      based dBT was found to be safe, of mild and transitory toxicity, and effective in
      long-term tumour control.

PMID- 11835113
TI  - The "metal transcription factor" MTF-1: biological facts and medical
      implications.
AB  - Metallothioneins (MTs) are a class of small, cysteine-rich proteins that have an
      important function in heavy metal metabolism and detoxification and in the
      management of various forms of cell stress. Several lines of evidence suggest a
      role for metallothioneins in therapy resistance of malignant tumours, regulation
      of blood pressure and protection against some neurological diseases. Basal and
      heavy metal-induced expression of the stress-inducible metallothionein-I and -II
      genes and some other stress-regulated genes depends on the zinc-finger
      transcription factor MTF-1. MTF-1 acts as a cellular stress-sensor protein and,
      besides its crucial role in metallothionein expression, is essential for liver
      development since mice null mutant for MTF-1 die in utero due to hepatocyte
      degeneration. Under pathological conditions, MTF-1 seems to be involved in
      clinically important processes such as tumour angiogenesis and drug resistance.
      It thus seems generally advisable to monitor MTF-1 activity in stress-related
      processes including aging and carcinogenesis.

PMID- 11835114
TI  - Critical appraisal of the diagnostics of 270 consecutive cases of suspected
      venous thromboembolism and established consequences at a non-university center.
AB  - QUESTIONS UNDER STUDY: Diagnostic strategies in venous thromboembolism (VTE) are
      subject to controversy and rapid change and are dependent on the availability of
      the specific tests. The aim was to critically analyse the diagnostic procedures
      in patients with VTE at an intermediate size, non-university hospital. METHODS:
      The diagnostic work up of 270 consecutive patients with suspected VTE disorders
      was analysed prospectively and the therapeutic decisions were monitored and
      compared with the actually implemented new standard evaluation which consists of
      a sequential application of the diagnostic tools (clinical probability, D-dimer
      compression ultrasound V/Q lung scan or CT). The patients were followed
      clinically for at least three months. RESULTS: 50% of the 55 patients with
      suspected deep vein thrombosis (DVT) and 35% of the 215 patients with suspected
      pulmonary embolism (PE) were found positive and were anticoagulated. The overall
      number of patients being anticoagulated was not significantly changed by the new
      procedure but approximately 30% of the additional examinations inclusive V/Q
      scans, spiral CT and compression ultrasound or phlebography could be saved. Our
      study and the follow up after the therapeutic decision indicate that 92% of the
      patients can be clearly and safely allocated, while the remainders are managed
      according to an essentially clinical decision. CONCLUSIONS: The vast majority
      (>90%) of the patients can be clearly diagnosed as positive or negative with the
      strategy presently used. A minority still requires an "overall decision". Our
      modified approach results in considerable cost savings.

PMID- 11835115
TI  - Compression stockings prophylaxis of emergent varicose veins in pregnancy: a
      prospective randomised controlled study.
AB  - QUESTIONS UNDER STUDY: To determine the efficacy of compression stockings in
      preventing emergent varicose veins in pregnancy. METHODS: A prospective
      randomised controlled study in the outpatient department of the University
      Hospital of Zurich, Switzerland, including women with uncomplicated pregnancies
      <12 weeks at outset of study. A no-stockings control group (n = 15) was compared
      with two treatment groups: group 1 (n = 12) wore compression class I stockings
      (18-21 mm Hg) on the left leg and class II stockings (25-32 mm Hg) on the right;
      in group 2 (n = 15), the compression classes were reversed. Stockings were worn
      from study entry to term. Endpoints were emergence and worsening of superficial
      varicose veins, long saphenous vein reflux at the sapheno-femoral junction, and
      leg symptoms (pain, discomfort, cramps) during pregnancy. RESULTS: Both classes
      of compression stockings failed to prevent the emergence of superficial varicose
      veins. However, long saphenous vein reflux at the sapheno-femoral junction was
      observed in the third trimester in only 1/27 treated women vs. 4/15 controls (p =
      0.047); in addition, more treated women reported improved leg symptoms (7/27 vs.
      0/15 controls; p = 0.045). Emergent varicose changes, however, did not differ
      significantly (7/14 controls vs. 5/12 in group 1 and 8/14 in group 2; 3x3 table,
      Fisher's exact = 0.94). CONCLUSIONS: Although compression stockings do not
      prevent the emergence of gestational varicose veins, they significantly decrease
      the incidence of long saphenous vein reflux at the sapheno-femoral junction and
      improve leg symptoms. Our results also suggest that superficial varices and deep
      venous insufficiency may have a different aetiology.

PMID- 11835117
TI  - Gene nutrient interactions in type 2 diabetes--a clinical perspective.

PMID- 11835116
TI  - Regression of HIV-associated pulmonary arterial hypertension and long-term
      survival during antiretroviral therapy.
AB  - In a 37-year-old patient HIV infection was diagnosed in June 1986. Eight years
      later the patient complained of increasing shortness of breath and occasional
      syncopes on exertion. He developed peripheral oedema and ascites.
      Echocardiography revealed severe pulmonary hypertension. Right ventricular
      systolic pressure (RVSP) was 77 mm Hg. There was no evidence of left ventricular
      dysfunction, valvular heart disease, thromboembolic disease or obstructive or
      restrictive lung disease, nor were there other known causes or risk factors of
      pulmonary hypertension. HIV-associated pulmonary arterial hypertension was
      diagnosed. Oral anticoagulation and zidovudine were begun, but RVSP rose to 96 mm
      Hg. After the introduction of lamivudine, and later stavudine and nelfinavir, HIV
      RNA copies decreased from 133 400 to below 50 copies per mL. Six years after the
      diagnosis of HIV-associated pulmonary arterial hypertension RVSP had continually
      fallen to 49 mm Hg and the grossly enlarged right heart dimensions had nearly
      normalised without vasodilator treatment. The patient remains in excellent health
      and his sole complaint is of mild dyspnoea on exertion.

PMID- 11835118
TI  - Insulin Lispro in pregnancy--retrospective analysis of 33 cases and matched
      controls.
AB  - AIMS/HYPOTHESIS: To evaluate if the application of Lispro insulin in pregnancy
      increases the risk for malformations or unusual pregnancy courses. METHODS:
      Diabetes specialists were contacted in Germany and Austria and asked to report
      women with diabetes who had been treated with Lispro during pregnancy.
      Furthermore they were asked to report another pregnant diabetic woman treated
      with regular insulin with similar HbA1c and age for each Lispro case. Following
      data were requested: age, first HbA1c in pregnancy and time of analysis, start
      and duration of Lispro treatment, ultrasound examination, chorionic villi biopsy,
      amniocentesis, unusual pregnancy courses, standard examination of the new-born
      for any malformation. Two-sided 95% confidence limits (95%-CI) for risk
      differences of proportions of malformations or unusual pregnancy courses were
      calculated. RESULTS: 33 pregnant diabetic women with Lispro and 27 with regular
      insulin treatment were analysed (mean age 28.3 years (17-41)and 30.1 (19-40);
      mean HbA1c 6.9% (4.5-10.7) and 6.8% (4.7-9.8), respectively). There were four
      malformations or unusual pregnancy course (spontaneous abortion; elective
      interruption because of multiple malformations; heart malformations and hyaline
      membrane syndrom; premature birth) in the Lispro and one malformation (dyplastic
      hip) in the regular insulin group. Risk differences in proportions of
      malformation or unusual pregnancy courses were 8% (95%-CI: - 5% to 21%).
      CONCLUSIONS/INTERPRETATION: Risk differences for malformations or unusual
      pregnancy courses were not higher in the insulin Lispro group compared to the
      controls. However, we observed four malformations or unusual pregnancy courses in
      the Lispro group. A case-control study is suggested to get a precise risk
      estimate.

PMID- 11835119
TI  - Complications, co-morbidity, and blood glucose control in type 2 diabetes
      mellitus patients in Germany--results from the CODE-2 study.
AB  - In this study, prevalence and incidence of complications as well as co-morbidity
      in type 2 diabetes patients in Germany were evaluated as part of a cost-of
      illness study (CODE-2(TM), Costs of Diabetes in Europe - Type 2)In a pre-study,
      197 general practitioners and diabetes specialists all over Germany provided data
      on the complication status of 2701 randomly selected patients with type 2
      diabetes. The patients were grouped into five mutually exclusive strata. This pre
      study was performed to generate a general overview on complication status to
      select proper patients for the main study. The main study was performed on
      stratified samples derived from the pre-study. Irrespective of the real
      prevalence of the five strata, an equal number of 160 were randomly selected from
      each stratum. Thus, rare complications were also covered in the study. Data from
      809 patients were collected retrospectively on the basis of medical files during
      interviews with the physician. To achieve representative estimates of absolute
      prevalence and incidence of diabetes-related complications in Germany, results
      were weighted using frequencies of the strata. Severe complications were
      diagnosed in 50% of these patients. Prevalences were: 10.56% myocardial
      infarction, 6.66% stroke, 3.97% foot ulcer, 2.30% amputations and 1.34%
      blindness. Overall incidences in the diabetes population were estimated at 0.78%
      myocardial infarction, 1.28% stroke and 0.80% amputations. 23% of the diabetes
      patients suffered from 2 or more complications. The complication status became
      considerably worse with increasing time since the diagnosis of diabetes. The mean
      HbA1c level was 7.51% (i.e. 122% of the upper limit of the respective normal
      ranges). The presence of complications and co-morbidity in type 2 diabetes
      patients was a frequent finding. This underlines the importance of complications
      in diabetes patients and the necessity to increase any means of prevention in
      order to relieve the personal and economic burden of type 2 diabetes.

PMID- 11835120
TI  - Technosphere/Insulin--proof of concept study with a new insulin formulation for
      pulmonary delivery.
AB  - Summary.Technosphere/Insulin (TI) is a formulation of regular human insulin and
      Technosphere, a new drug delivery system for pulmonary administration. The
      formulation is designed for efficient transport of insulin across the intact
      respiratory epithelium into the systemic circulation. We have investigated the
      pharmacodynamic and pharmacokinetic properties of Technosphere/Insulin in five
      healthy, non-smoking volunteers. In an open, randomized, three-way crossover
      study, subjects received 5 IU regular human insulin (HI) intravenously, 10 IU HI
      subcutaneously; and 100 IU TI via inhalation using a small commercially available
      asthma inhaler. The time action profiles of all three insulin formulations were
      assessed by the euglycemic glucose clamp technique on three different study days.
      Glucose infusion rates were monitored from 2 h before until 6 h after insulin
      administration. Other study measures were serum insulin, serum C-peptide
      concentrations, and safety parameters. The inhalation of TI was well tolerated.
      The time to peak action was significantly shorter with both i.v. injection and
      inhalation, as compared to s.c. (14 +/- 6 min and 39 +/- 36 min vs. 163 +/- 25
      min; p < 0.0002 and p < 0.007 (mean +/- SD)). The metabolic effect during the
      first 3 h after insulin administration was higher with inhaled TI than with HI
      s.c. (AUC0-180 for glucose infusion rate: 1.94 +/- 0.77 mg/kg * min vs. 1.15 +/-
      0.50 mg/kg * min; p < 0.04). Relative and absolute bioavailability for the first
      3 h were 26 +/- 12% and 15 +/- 5% respectively (6 h: 16 +/- 8 and 16 +/- 6%). We
      conclude that inhalation of TI leads to a rapid onset of metabolic action
      resembling the effect observed with i.v. administration of regular HI. Despite
      the use of a common asthma inhaler, bioavailability over the three hour prandial
      period was substantially greater than with other reported pulmonary systems.
      Therefore, inhalation of Technosphere/Insulin may become a suitable and
      attractive alternative for prandial insulin delivery, especially for patients
      with type 2 diabetes mellitus.

PMID- 11835121
TI  - Pathogenesis of diabetic neuropathy--do hyperglycemia and aldose reductase
      inhibitors affect neuroactive steroid formation in the rat sciatic nerves?
AB  - The activation of the polyol pathway through aldose reductase (AR) might be
      involved in diabetic neuropathy. A considerable structural similarity exists
      between AR and 3alpha-hydroxysteroid dehydrogenase (3alpha-HSD) (both belonging
      to aldo-keto reductase superfamily); 3alpha-HSD forms 5alpha-reduced-3alpha
      hydroxylated steroids, possibly possessing neurotrophic functions. Aim of these
      experiments was to test "in vitro" in rat sciatic nerves, whether glucose
      concentrations in the diabetic range might affect the capacity of 3alpha-HSD to
      transform dihydroprogesterone (DHP) into tetrahydroprogesterone (THP), a steroid
      proved to possess neurotrophic effects. The capability of AR inhibitors, drugs
      used to avoid diabetic complications, to decrease THP formation was also
      assessed. 3alpha-HSD activity was evaluated by the conversion of labelled DHP
      into THP (in a single case dihydrotestosterone was used as substrate, and the
      corresponding 3alpha-hydroxylated metabolite was evaluated). Freshly prepared rat
      sciatic nerve homogenates were used as source of the enzyme. Whole brain, liver
      and prostate served as "control" tissues. The results show that glucose added up
      to a concentration of 400 mg/dL (well above the euglycemic upper level) does not
      affect the 3alpha-HSD activity in the sciatic nerve and in the other tissues
      considered. Similarly, when the enzyme was challenged by two AR inhibitors,
      tolrestat and sorbinil, added in a concentration about 10 times higher than their
      IC50 for AR, no significant changes were observed. Analogous results were
      achieved when DHT was used in presence of glucose (400 mg/dL) and sorbinil. We
      conclude that hyperglycemia or the administration of the AR inhibitors do not
      affect 3alpha-HSD activity in peripheral nerves and therefore do not reduce the
      formation of steroid metabolites possibly endowed with neurotrophic action.

PMID- 11835122
TI  - Differences in tumor cell proliferation, HLA DR expression and lymphocytic
      infiltration in various types of thyroid carcinoma.
AB  - The proliferative activity of various thyroid carcinoma forms (papillary,
      follicular, medullary, anaplastic) was investigated using two second generation
      antibodies against Ki-67 that can be used on paraffin-embedded sections. Poorly
      differentiated carcinomas had a higher proliferation than well-differentiated
      forms. Papillary carcinoma stained significantly more often with either antibody
      than follicular carcinoma. A solid growth pattern correlated with high Ki-67
      expression while an increase in follicular elements and a high amount of psammoma
      bodies coincided with lower proliferation.HLA class II expression and
      infiltrating lymphocytes are prerequisites for an immune defense against cancer.
      In this study, HLA DR was increased in poorly-differentiated carcinomas,
      especially in the anaplastic type. The increase in HLA DR was correlated with Ki
      67 positivity. On tumor-infiltrating lymphocytes, HLA DR was well expressed in
      papillary carcinoma and relatively poorly expressed in follicular carcinoma, but
      there was no significant correlation with carcinoma type or morphological
      parameters. CD 45 R0, which might recognize memory cells, was found mostly in
      anaplastic and papillary carcinomas, and correlated well with HLA DR expression.
      These findings imply that an active but variable immune response is present in
      thyroid carcinoma.

PMID- 11835123
TI  - Differential diagnosis of hyperthyroidism: Doppler sonographic quantification of
      thyroid blood flow distinguishes between Graves' disease and diffuse toxic
      goiter.
AB  - The aim of our study was to evaluate the usefulness of color duplex sonography to
      distinguish Graves' disease from diffuse toxic goiter. 24 patients with Graves'
      disease and 13 patients with diffuse toxic goiter underwent B-mode- and color
      duplex sonography of the thyroid gland. All patients had hyperthyroidism and
      elevated (99m)Tc-uptake. Spectral Doppler recordings were obtained at all thyroid
      arteries. Representative color flow maps of the thyroid gland were analyzed,
      calculating the percentage area of the thyroid gland, occupied by color pixels
      (color pixel density). The B-mode ultrasound pattern was subjectively assessed on
      a 4-point rating scale. In patients with Graves' disease the mean peak systolic
      velocity (PSV) (SD) was 110 (+/- 49) cm/s, the mean volume flow rate (VFR) was
      123 ( +/- 67) ml/min and the mean color pixel density (CPD) was 33 (+/- 12) %.
      For patients with diffuse toxic goiter mean PSV (SD) was 43 ( +/- 9) cm/s (p <
      0.001), mean VFR was 23 (+/- 10) ml/min (p < 0.001) and mean CPD was 9 (+/- 6) %
      (p = 0.007). CPD and spectral duplex recordings were positively correlated
      (CPD/PSV: rs = 0.77, CPD/VFR: rs = 0.75; p < 0.0001). No significant differences
      were observed concerning RI values. Sensitivity was 87% and specificity 92% for
      CPD and VFR and 87% and 100% for PSV. We conclude, that color duplex sonography
      can reliably distinguish diffuse toxic goiter from Graves' disease and therefore
      contributes significantly to the differential diagnosis of hyperthyroidism in
      diffuse thyroid disease.

PMID- 11835124
TI  - Sex steroids regulate TSH-induced thyroid growth during sexual maturation in
      Wistar rats.
AB  - Sex steroids have been reported to influence thyroid pathogenesis in human and
      experimental animals. However, there is no much report on the effect of sex
      steroids in the growth of normal thyroid. The present study is an attempt to know
      TSH-induced thyroid growth during sexual maturation in Wistar rats. Wistar rats
      of day 1 to day 150 postpartum (pp) were used in the present study. Thyroid
      growth indices such as absolute and relative thyroid weights, concentration of
      DNA in the thyroid, mitotic index and numerical density of thyrocytes, hormonal
      profiles in the serum and thyroid tissue such as thyrotropin (TSH), thyroid
      hormones, testosterone and estradiol, and receptors for TSH, androgen and
      estrogen in the thyroid were estimated. A gender-specific shift in the pattern of
      serum TSH and TSH-R was observed during 30-45 days of postnatal life, the period
      at which steroidogenesis by testes or ovaries of rats are reactivated.
      Testosterone in males and estradiol in females modulate thyroid growth through
      TSH. It is concluded from the present study that changes in the sex steroid
      status between male and female rats have a definite influence on the pattern of
      thyroid growth and TSH.

PMID- 11835125
TI  - Renin producing neuroendocrine pancreatic carcinoma--a case report and review of
      the literature.
AB  - A 44 year old male patient presented with severe hypertension. The diagnostic
      work-up revealed elevated levels of plasma renin activity (about 10 times the
      upper limit of normal) in the presence of normal plasma aldosterone levels and
      serum potassium concentrations. Renovascular disease was excluded by angiography.
      Selective renal vein sampling did not show any renin gradient. CT-scans of the
      abdomen demonstrated normal morphology of the kidneys and adrenals but revealed a
      big mass in the pancreatic corpus and tail with infiltration of the splenic vein
      and the presence of enlarged local lymph nodes. The endocrine nature of the
      pancreatic mass was further supported by a positive octreotide scintigraphy scan.
      Surgical removal of the tumor by left sided pancreatectomy combined with
      splenectomy resulted in rapid normalization of elevated renin concentrations as
      well as blood pressure. Histological examination of the tumor tissue revealed the
      presence of a neuroendocrine pancreatic carcinoma. Highly (x 70) elevated renin
      levels were detected by radioimmunoassay in the tumor tissue. To our knowledge
      this is the first renin-producing neuroendocrine pancreatic carcinoma described
      in the literature. The present paper describes the case in detail and reviews the
      available literature on clinical symptomatology, diagnosis and treatment of renin
      producing tumors.

PMID- 11835133
TI  - Electrochemical monitoring of cell behaviour in vitro: a new technology.
AB  - This article describes a novel electrochemical technique for the real-time
      monitoring of changes in the behaviour of adherent human cells in vitro: i.e., a
      biosensor that combines a biological recognition mechanism with a physical
      transduction technique, described collectively as Oncoprobe. Confluent viable
      cells adherent to gold electrodes (sensors) modify the extracellular
      microenvironment at the cell:sensor interface to produce a change in the
      electrochemical potential compared to that measured in the absence of cells. The
      potential was measured as an open circuit potential (OCP) with respect to a
      saturated calomel reference in the bulk culture medium. Typical OCP values for
      confluent cultures of human breast carcinoma cells, 8701-BC, approximated -100 mV
      compared with cell-free values of approximately -15 mV. The OCP for 8701-BC cells
      was modified in response to temperature changes over the range 32 to 40 degrees C
      and also to treatments with phytohemagglutinin (PHA, 25 microg/mL), cycloheximide
      (30 microM) and interleukin-1 beta (IL-1, 0.5 ng/mL) over 24 h. Cultures of
      synovial fibroblasts also responded to the same treatments with similar
      responses, producing negative shifts in the OCP signal with PHA and IL-I, but a
      positive shift in OCP signal with cycloheximide, all relative to the untreated
      control cultures. From experimental data and theoretical considerations it is
      proposed that the cell-derived signals are mixed electrode potentials reflecting
      a "conditioned," more reducing environment at the cell:sensor interface. Only
      viable cells caused a negative shift in the OCP signal, this being lost when
      cells were rendered nonviable by formalin exposure. This technology appears
      unique in its ability to passively "listen in" on cell surface activities,
      suggesting numerous applications in the fields of drug discovery, chemotherapy,
      and cell behaviour.

PMID- 11835134
TI  - Calculability analysis in underdetermined metabolic networks illustrated by a
      model of the central metabolism in purple nonsulfur bacteria.
AB  - Metabolite balancing has turned out to be a powerful computational tool in
      metabolic engineering. However, the linear equation systems occurring in this
      analysis are often underdetermined. If it is difficult or impossible to find the
      missing constraints, it is nevertheless feasible in some cases to determine the
      values of a subset of the unknown rates. Here, a procedure for finding out which
      reaction rates can be uniquely calculated in underdetermined metabolic networks
      and computing these rates is given. The method is based on the null space to the
      stoichiometry matrix corresponding to the reactions with unknown rates. It is
      shown that this method is considerably easier to handle than an algorithm given
      previously (Van der Heijden et al., 1994a). Furthermore, a useful elementary
      representation of the null space is presented which is closely related with the
      elementary flux modes. This unique representation is central to a more general
      approach to observability/calculability analysis. In particular, it allows one to
      find, in an easy way, those sets of measurable rates that enable a calculation of
      a certain unknown rate. Besides, rates which are never calculable by metabolite
      balancing may be easily detected by this method. The applicability of these
      methods is illustrated by a model of the central metabolism in purple nonsulfur
      bacteria. The photoheterotrophic growth of these representatives of anoxygenic
      photosynthetic bacteria is stoichiometrically analyzed. Interesting metabolic
      constraints caused by the necessary balancing of NADPH can be detected in a
      highly underdetermined system. This is, to our knowledge, the first application
      of stoichiometric analysis to the metabolic network in this bacteria group using
      metabolite balancing techniques. A new software tool, the FluxAnalyzer, is
      introduced. It allows quantitative and structural analysis of metabolic networks
      in a graphical user interface.

PMID- 11835135
TI  - Screening of various glycosidases for the synthesis of octyl glucoside.
AB  - Thirteen glycosidases of microbial origin and almond beta-glycosidase were
      assayed in octanol/DMF (80:20, v/v), using a combination of hydrolysis,
      transglycosylation, and condensation reactions, in order to assess their
      potential for the production of alkyl glucosides. The two mesophile enzymes were
      highly impaired by the organic media. Three of the 11 thermophile enzymes gave
      interesting results in the hydrolysis and transglycosylation reactions, but they
      were highly inhibited by glucose. This made their use in a condensation reaction
      less interesting than the use of almond beta-glucosidase, which has a lower
      activity but shows less inhibition by the glucose.

PMID- 11835136
TI  - Miniaturized amperometric flow immunoassay system using a glass fiber membrane
      modified with anion.
AB  - This paper describes a miniaturized amperometric flow immunoassay system using a
      glass fiber membrane modified with anion. The glass fiber membrane was
      functionally modified with gamma-glycidoxypropyltrimethoxysilane and sodium
      thiosulfate and was used for separation of protein. Anti-human chorionic
      gonadotrophin (HCG) immunoglobulin G (IgG) antibody conjugated with
      ferrocenemonocarboxylic acid (Fc), namely, Fc-conjugated IgG (Fc-IgG), was used
      as a novel analytical reagent. HCG and Fc-IgG complexes were separated from free
      Fc-IgG based on differences in isoelectric point (pI) using the glass fiber
      membrane modified with a thiosulfonyl acid functional group. The assay yields a
      linear relationship between current and HCG concentration in the range of 0-2000
      mIU/mL. This simple technique enables the assay of HCG within 2 min. The modified
      glass fiber membrane was regenerated by occasional elution with malonate buffer
      (pH 6.0) containing 0.5 M NaCl, to remove free Fc-IgG. Free Fc-IgG recovered in
      this manner could be reused up to eight times without significant decreases in
      sensitivity. This miniaturized amperometric flow immunoassay requires only minute
      quantities of serum and generates highly reproducible results.

PMID- 11835137
TI  - Modeling of the biotransformation of crotonobetaine into L-(-)-carnitine by
      Escherichia coli strains.
AB  - A simple unstructured model, which includes carbon source as the limiting and
      essential substrate and oxygen as an enhancing substrate for cell growth, has
      been implemented to depict cell population evolution of two Escherichia coli
      strains and the expression of their trimethylammonium metabolism in batch and
      continuous reactors. Although the model is applied to represent the trans
      crotonobetaine to L-(-)-carnitine biotransformation, it is also useful for
      understanding the complete metabolic flow of trimethylammonium compounds in E.
      coli. Cell growth and biotransformation were studied in both anaerobic and
      aerobic conditions. For this reason we derived equations to modify the specific
      growth rate, mu, and the cell yield on the carbon source (glycerol), Y(xg), as
      oxygen increased the rate of growth. Inhibition functions representing an excess
      of the glycerol and oxygen were included to depict cell evolution during extreme
      conditions. As a result, the model fitted experimental data for various growth
      conditions, including different carbon source concentrations, initial oxygen
      levels, and the existence of a certain degree of cell death. Moreover, the
      production of enzymes involved within the E. coli trimethylammonium metabolism
      and related to trans-crotonobetaine biotransformation was also modeled as a
      function of both the cell and oxygen concentrations within the system. The model
      describes all the activities of the different enzymes within the transformed and
      wild strains, able to produce L-(-)-carnitine from trans-crotonobetaine under
      both anaerobic and aerobic conditions. Crotonobetaine reductase inhibition by
      either oxygen or the addition of fumarate as well as its non-reversible catalytic
      action was taken into consideration. The proposed model was useful for describing
      the whole set of variables under both growing and resting conditions. Both E.
      coli strains within membrane high-density reactors were well represented by the
      model as results matched the experimental data.

PMID- 11835138
TI  - Direct recovery of glutathione S-transferase by expanded bed adsorption: anion
      exchange as an alternative to metal affinity fusions.
AB  - The use of expanded beds of ion-exchange adsorbents for the direct recovery of a
      recombinant intracellular protein, glutathione S-transferase (GST), from
      unclarified Escherichia coli homogenates is described. The results form the basis
      for a comparison between this approach for purifying GST and a chelating fusion
      strategy and highlight the need to consider the additional costs entailed by
      these more-complicated approaches. The separation performance was investigated
      with respect to choice of anion or cation exchanger, adsorption pH, load volume,
      sample preparation, and stepwise elution protocol. Anion exchange was found to be
      more appropriate than cation exchange, as the low pHs involved in the latter
      caused a loss of activity. The optimal pH for adsorption was found to be 9 with a
      dynamic capacity from clarified homogenate in packed mode of 112 U mL(-1) (11.2
      mg GST mL(-1)). As increasing volumes of unclarified homogenate were applied to
      the expanded bed, the yield of GST in the eluate decreased, and the purification
      factor was found to increase and then decrease. This was due to the displacement
      of weakly bound proteins by GST and then its displacement by even more strongly
      binding proteins. The dynamic capacity of the anion exchanger, STREAMLINE DEAE,
      from unclarified homogenate in expanded mode decreased slightly to 85 U mL(-1)
      (8.5 mg GST mL(-1)). The elution protocol for GST from the anion exchanger was
      then adjusted to try to maximize the degree of purification. Anion exchange
      expanded bed adsorption of GST from unclarified E. coli homogenate gave an eluted
      yield of 95.7% and 1.64-fold purification. Interestingly, a decrease in the
      expression level of GST in the feedstream from 23 down to 13% caused a decrease
      in the dynamic capacity from 85 to 14.5 U mL(-1) whereas the degree of
      purification remained similar.

PMID- 11835139
TI  - Ethylene oxide and propylene oxide random copolymer/sodium chloride aqueous two
      phase systems: wetting and adsorption on dodecyl-agarose and polystyrene.
AB  - Liquid/liquid partition chromatography is a mild yet powerful separation method
      for a variety of biological materials. This work demonstrates that it should be
      feasible to immobilize an ethylene oxide-propylene oxide (EO/PO) random copolymer
      solution and to use a solution of NaCl equilibrated against the polymer solution
      as the mobile-phase (poly (EO-PO) [P(EO-PO)] and NaCl form two aqueous phases
      known as aqueous two-phase systems). Three random copolymers with different
      molecular weights and EO/PO ratios were used. Dodecyl-agarose and polystyrene
      were tested as possible supports. The wetting energies of the aqueous two-phase
      systems on these two kinds of surfaces were calculated as well as contact angles
      for each phase on the same surfaces. Finally, the thickness of P(EO-PO)
      adsorption layers on polystyrene lattices were measured by dynamic light
      scattering. Contact angle measurements indicate that indeed some EO/PO copolymers
      preferentially wet hydrophobic substrates, forming thin films.

PMID- 11835140
TI  - A mass balance study to assess the extent of contaminant removal achieved in the
      operations for the primary recovery of plasmid DNA from Escherichia coli cells.
AB  - Mass balances were performed on an alkaline lysis operation for the primary
      recovery of supercoiled plasmid DNA as part of a process for plasmid gene
      preparation. Escherichia coli DH5alpha/pSVbeta was cultured in defined medium by
      fed-batch fermentation and harvested at the end of the exponential phase.
      Alkaline lysis of the recombinant cells was performed at fixed shear rates
      ranging between 46 and 461 s(-1), with neutralization 100 and 300 s after the
      initiation of the lysis. Mass balance calculations were used to optimize the
      operating conditions for carrying out the alkaline lysis operation. The results
      indicated that a plasmid yield of 75% and purity with respect to total DNA of 60%
      were achievable during the primary recovery operation. The influences of key
      contaminants, including the soluble proteins and the suspended solids, as they
      bear on the subsequent purification operations, were evaluated and discussed.

PMID- 11835141
TI  - Application of neural network for simulation of upflow anaerobic sludge blanket
      (UASB) reactor performance.
AB  - Up-flow anaerobic sludge blanket (UASB) reactors are being used with increasing
      regularity all over the world, especially in India, for a variety of wastewater
      treatment operations. Consequently, there is a need to develop methodologies
      enabling one to determine UASB reactor performance, not only for designing more
      efficient UASB reactors but also for predicting the performance of existing
      reactors under various conditions of influent wastewater flows and
      characteristics. This work explores the feasibility of application of an
      artificial neural network-based model for simulating the performance of an
      existing UASB reactor. Accordingly, a neural network model was designed and
      trained to predict the steady-state performance of a UASB reactor treating high
      strength (unrefined sugar based) wastewater. The model inputs were organic
      loading rate, hydraulic retention time, and influent bicarbonate alkalinity. The
      output variables were one or more of the following, effluent substrate
      concentration (Se), reactor bicarbonate alkalinity, reactor pH, reactor volatile
      fatty acid concentration, average gas production rate, and percent methane
      content of the gas. Training of the neural network model was achieved using a
      large amount of experimentally obtained reactor performance data from the reactor
      mentioned above as the training set. Training was followed by validation using
      independent sets of performance data obtained from the same UASB reactor.
      Subsequently, simulations were performed using the validated neural network model
      to determine the impact of changes in parameters like influent chemical oxygen
      demand (COD) concentration and hydraulic retention time on the reactor
      performance. Simulation results thus obtained were carefully analyzed based on
      qualitative understanding of UASB process and were found to provide important
      insights into key variables that were responsible for influencing the working of
      the UASB reactor under varying input conditions.

PMID- 11835142
TI  - Dependence of morphology on agitation intensity in fed-batch cultures of
      Aspergillus oryzae and its implications for recombinant protein production.
AB  - We previously reported that, although agitation conditions strongly affected
      mycelial morphology, such changes did not lead to different levels of recombinant
      protein production in chemostat cultures of Aspergillus oryzae (Amanullah et al.,
      1999). To extend this finding to another set of operating conditions, fed-batch
      fermentations of A. oryzae were conducted at biomass concentrations up to 34 g
      dry cell weight/L and three agitation speeds (525, 675, and 825 rpm) to give
      specific power inputs between 1 and 5 kWm(-3). Gas blending was used to control
      the dissolved oxygen level at 50% of air saturation except at the lowest speed
      where it fell below 40% after 60-65 h. The effects of agitation intensity on
      growth, mycelial morphology, hyphal tip activity, and recombinant protein
      (amyloglucosidase) production in fed-batch cultures were investigated. In the
      batch phase of the fermentations, biomass concentration, and AMG secretion
      increased with increasing agitation intensity. If in a run, dissolved oxygen fell
      below approximately 40% because of inadequate oxygen transfer associated with
      enhanced viscosity, AMG production ceased. As with the chemostat cultures, even
      though mycelial morphology was significantly affected by changes in agitation
      intensity, enzyme titers (AGU/L) under conditions of substrate limited growth and
      controlled dissolved oxygen of >50% did not follow these changes. Although the
      measurement of active tips within mycelial clumps was not considered, a
      dependency of the specific AMG productivity (AGU/g biomass/h) on the percentage
      of extending tips was found, suggesting that protein secretion may be a bottle
      neck in this strain during fed-batch fermentations.

PMID- 11835144
TI  - Substrate inhibition mode of omega-transaminase from Vibrio fluvialis JS17 is
      dependent on the chirality of substrate.
AB  - Substrate inhibition is a common phenomenon in enzyme chemistry, which is
      observed only with a fast-reacting substrate enantiomer. We report here for the
      first time substrate inhibition of an enantioselective enzyme by both substrate
      enantiomers. The enantioselective substrate inhibition, i.e., different mode of
      inhibition by each substrate enantiomer, of (S)-specific omega-transaminase was
      found with various chiral amines. A kinetic model based on ping-pong bi-bi
      mechanism has been developed and kinetic parameters were measured. The kinetic
      model reveals that the inhibition by (R)-amine results from formation of
      Michaelis complex with enzyme-pyridoxal 5'-phosphate, whereas the inhibition by
      (S)-amine results from the formation of the complex with enzyme-pyridoxamine 5'
      phosphate. Substrate inhibition constants (K(SI)) of each (S)-enantiomer of four
      chiral amines showed a linear correlation with those of cognate (R)-amines. Such
      a correlation was also found between the K(SI) values and Michaelis constants of
      (S)-amines. These correlations indicate that recognition mechanisms and active
      site structures of both enzyme-pyridoxal 5'-phosphate, enzyme-pyridoxamine 5'
      phosphate are similar. Taken together with the results, high propensity for non
      productive substrate binding strongly suggests that binding pockets of the omega
      transaminase is loosely defined, which accounts for the enantioselective
      substrate inhibition.

PMID- 11835143
TI  - Yeast-mediated preparation of l-PAC in an organic solvent.
AB  - The yeast-mediated acyloin condensation of benzaldehyde and pyruvic acid to form
      l-PAC occurs in a petroleum spirit solvent system at room temperature with
      moderate conversion (30%) and high enantioselectivity (86%ee) after 24 h. The
      addition of a small amount of ethanol (0.5% mL) to the reaction mixture inhibits
      the formation of the side product benzyl alcohol and increases the conversion to
      l-PAC. Conducting the reaction using 13C labeled pyruvate indicated that the
      pyruvate was incorporated into the l-PAC and that the excess pyruvate was
      converted into ethanol. Conducting the reaction at 5 degrees C results in similar
      conversion but higher enantioselectivity.

PMID- 11835145
TI  - Monitoring of temperature effects on animal cell metabolism in a packed bed
      process.
AB  - Animal cell (Chinese Hamster Ovary) concentration was determined on-line in a
      packed bed process using dielectric spectroscopy. This enabled the evaluation of
      the effect of temperature on specific metabolic rates during 3 months of
      continuous culture. The effect of low cultivation temperature on cell growth and
      metabolism was monitored, and the data were used for process development. At 37
      degrees C cells grew exponentially with a specific growth rate of 0.038 d-1 and
      specific glucose uptake and lactate production rates increased continually.
      Reduction of the temperature to 33.5 degrees C resulted in a lowering of these
      metabolic rates while having no effect on cell proliferation. Subsequent
      reduction of the temperature to 32 degrees C resulted in stabilization of the
      cell concentration at a high density (3.6 x 10(7) cell per mL of packed bed). In
      addition, the specific production rate of the protein of interest increased by a
      factor of 6 compared to the value at 37 degrees C. During the stationary phase at
      32 degrees C, all other specific metabolic rates could be controlled to low and
      constant levels.

PMID- 11835146
TI  - Evidence of a right-shift factor affecting infant hand-use preferences from 7 to
      11 months of age as revealed by latent class analysis.
AB  - Infant hand-use preferences for apprehending objects were assessed three times at
      7, 9, and 11 months of age for 154 infants (79 males) using a reliable and valid
      procedure. Two classification procedures (differing in Type I classification
      error rates) were used to identify an infant's preference (right, left, no
      preference) at each age, and these data were examined using two- and three-group
      latent class analysis models. These analyses revealed the importance of using a
      handedness classification procedure with low Type I error rates and evidence of a
      right-shift factor similar to that expressed in child and adult handedness. Thus,
      infant hand-use preferences for apprehending objects are likely a developmental
      precursor of adult handedness. The relation of the right-shift factor to
      increased susceptibility to social influences during development and the
      evolution of human abilities also is discussed.

PMID- 11835147
TI  - The sleep of co-sleeping infants when they are not co-sleeping: evidence that co
      sleeping is stressful.
AB  - Co-sleeping proponents consider the practice to be "natural" and a potential
      protection against sudden infant death syndrome (SIDS); others consider the
      practice of an infant sleeping in the parents' bed for prolonged periods at night
      to place an infant at risk for harm or death. For this study, co-sleeping was
      investigated from a different perspective, that is, as a significant early
      experience to investigate as it may have implications for the infant's
      development. The sleep of 101 normal, full-term infants was recorded
      nonintrusively in the home for 24 hr periods when they were 5 weeks and 6 months
      old. Infants were assigned to three groups: short-term co-sleepers, long-term co
      sleepers, and non-co-sleepers. Their sleep states and wakefulness were compared
      at the two ages and over age. At 5 weeks and 6 months, the long-term co-sleeping
      infants differed significantly from the non-co-sleepers on a number of measures:
      At 5 weeks, they showed more quiet sleep and longer bouts of quiet sleep; and at
      6 months, they also showed less active sleep, fewer arousals in active sleep, and
      less wakefulness. Each of these differences indicates a markedly lower arousal
      level in the long-term co-sleeping infants. This sleep pattern has been
      repeatedly found to be an indicator of stress. We infer that a major source of
      stress for these infants is the experience of sleep disturbance documented for
      infants when they were co-sleeping. Based on extensive evidence for long-term
      effects of early stress, we conclude that co-sleeping should have significant
      implications for infants' neurobehavioral development.

PMID- 11835148
TI  - Minimum duration of reactivation at 3 months of age.
AB  - Briefly exposing subjects to an isolated component of an event after they have
      forgotten can reactivate their memory of it, leading to renewed retention on an
      ensuing test. In two experiments with forty-eight 3-month-old infants, we asked
      what minimum duration of a reactivation treatment could recover their forgotten
      memory of an operant mobile task and whether the minimum duration was affected by
      how long the memory was forgotten. In Experiment 1, the minimum duration for
      reactivating the memory 1 week after forgetting was 120 s-substantially longer
      than the minimum duration required for reactivation at 6 months after the same
      relative delay. In Experiment 2, the minimum effective duration for reactivation
      increased linearly with the time since forgetting, from 7.5 s after 1 day to 180
      s after 3 weeks. This study reveals that the duration of an effective memory
      prime is directly related to age and to memory accessibility.

PMID- 11835149
TI  - Rising cortisol at childcare: relations with nap, rest, and temperament.
AB  - An unexpected rise in cortisol across the day in full-day, center-based childcare
      has been recently observed. Most of the children in these studies exhibited the
      rise across the day at childcare, but the expected drop at home. Possible
      explanations include more or less napping at childcare than at home. This study
      measured cortisol during childcare at 10:30 a.m., pre-rest, post-rest, and 3:30
      p.m. for 35 children, and at 10:30 a.m. and 3:30 p.m. at home for 8 children.
      Duration and quality of rest were coded during nap periods. For 91% of children,
      cortisol rose at childcare and for 75% dropped at home. None of the napping
      variables were related to the rise at childcare nor were differences found
      between home and childcare rest. Factors other than daytime rest periods seem
      likely to account for the rise in cortisol across the childcare day, possibly
      factors involving the interactional demands of group settings during this
      developmental period.

PMID- 11835150
TI  - The anterior attention network: associations with temperament and neuroendocrine
      activity in 6-year-old children.
AB  - The capacity to effortfully control or regulate behavior is of central importance
      in social development. Individual differences in effortful control have been
      hypothesized to reflect biologically based, temperamental variation among
      children. Posner and Rothbart (1994, 1998) have argued that the anterior
      attention system, which includes areas of the midprefrontal cortex, underlies
      effortful control capabilities. Furthermore, components of the anterior
      attentional system are believed to be involved in the regulation of reactive,
      emotion-related system, such as the hypothalamic-pituitary-adrenocortical system.
      We assessed 58 six-year-old children's performance on neuropsychological tasks
      that have been found in functional imaging studies to involve the anterior brain
      regions which Posner (1995) describes as comprising the anterior attentional
      system. We then related performance on these tasks to delay of gratification
      tasks and parent report of temperament and behavior problems as well as home and
      laboratory cortisol levels. Results provide some support for Posner and
      Rothbart's model and suggest a relationship between the anterior attentional
      system and cortisol regulation. However, these data also illustrate the
      multifaceted nature of effortful control and the need for care when attempting to
      understand the neural systems involved in the effortful regulation of behavior.

PMID- 11835151
TI  - Fetal responsiveness to maternal passive swinging in low heart rate variability
      state: effects of stimulation direction and duration.
AB  - Pregnant women, carrying end of gestation fetuses (38-41 weeks gestational age)
      were either gently rocked in an anterior posterior plane in a rocking chair or
      gently swayed laterally in a garden glider. Stimulation lasted for either 5 or 26
      s (R5 & R26, SW5 & SW26). Fetal heart rate (HR) (bpm) and ultrasonically detected
      fetal movements were recorded 26 s before and during stimulation. Heart rate data
      were processed two ways: (a) ANOVAs performed on average values for each group
      and (b) comparisons of the proportion of subjects in each group showing HR
      accelerative change (AC), HR decelerative change (DC), or no change (NC) using
      chi2 statistics. HR direction and amplitude of changes were determined with the
      help of a conservative procedure previously developed and fitted to
      multidirectional HR responses (Lecanuet, Granier-Deferre, Jacquet, & Busnel,
      1992). Results of ANOVAs indicated that a 26-s rocking stimulation induced a
      significant average HR acceleration (4.53 bpm) compared to a nonstimulated
      (control) group. Five seconds of rocking had a weaker, but still significant,
      effect on HR acceleration, but the two swaying conditions did not reliably affect
      either the HR or behavioral measures. Processing data nonparametrically confirmed
      that R26 stimulation evoked mostly AC (72%) and identified a gradual decrement of
      AC and DC percentage responses from Group R5, SW26 to Group SW5 while NC
      percentages raised. Hypotheses concerning the target sense activated by this
      stimulation were considered in relation to responses to auditory stimuli.

PMID- 11835152
TI  - Long-term retention of spatial navigation by preweanling rats.
AB  - The present study was designed to examine retention of spatial information in the
      immature, Fischer-344N rat using a savings paradigm. Following training to locate
      a hidden platform using extramaze cues, preweanling animals (17 days of age) were
      immediately probed by testing in the tank with the platform removed. One week
      later, pups (26 days of age) were given an additional four training trials
      immediately followed by a second probe test to examine the animals' memory for
      the location of the platform. Animals that received initial training at 17 days
      of age demonstrated significant savings of information when tested after the
      retention interval. These data replicate our recent report of spatial navigation
      capabilities in the preweanling rat, and extend those findings by demonstrating
      that preweanling spatial navigation performance permits more rapid and accurate
      navigation following a 7-day retention interval after a "reinstatement"
      insufficient to produce accurate navigation in maturation controls.

PMID- 11835153
TI  - Hydroxyapatite deposition by electrophoresis on titanium sheets with different
      surface finishing.
AB  - Hydroxyapatite coatings are commonly applied to metallic biomedical implants to
      accelerate osseointegration. These coatings, usually produced by plasma spray
      techniques, can be obtained by alternative processes, like biomimetic process,
      electrolytic deposition, or electrophoretic process as well. Electrophoretic
      deposition of hydroxyapatite exhibits several advantages like simplicity and low
      cost. In this article, titanium sheets with three different surface finishing
      were coated with hydroxyapatite by using electrophoresis. Surface treatments
      include: (1) abrading with SiC paper; (2) abrading with SiC paper plus
      electrolytic etch with H3PO4 solution; and (3) blasting with alumina powder
      followed by etch with a solution containing H2O2 and HF. Stoichiometric
      hydroxyapatite was used to coat titanium sheets. Blasted samples were also coated
      using a calcium-deficient hydroxyapatite. SEM, XRD, and FTIR were employed to
      characterize titanium substrates and coatings produced. Results show that
      electrophoretic process can produce a uniform thin layer, satisfactorily adhered,
      of hydroxyapatite on treated titanium samples. Furthermore, sintering at 800
      degrees C do not promote the decomposition of calcium-deficient hydroxyapatite.

PMID- 11835154
TI  - Alteration of leukocyte motility on plasma-conditioned prosthetic biomaterial,
      ePTFE, via a flow-responsive cell adhesion molecule, CD43.
AB  - The physiologic determinants of leukocyte migration on vascular prosthetic
      biomaterials remain poorly understood, despite their relevance to the control of
      periprosthetic infection. Using hemodynamic exposure of human polymorphonuclear
      leukocytes adherent to expanded polytetrafluoroethylene (ePTFE) in vitro, we
      investigated the role of fluid shear in regulating leukocyte migratory behavior
      on plasma-adsorbed, prosthetic vascular biomaterial. The presence of flow at a
      wall shear stress of 25 dyn/cm(2) increased the degree of leukocyte displacement
      along the flow direction without altering the degree of overall cell attachment.
      Moreover, plasma-ePTFE elicited a lower overall degree of displacement under flow
      in comparison with untreated ePTFE. We further probed the molecular level
      regulation of leukocyte migratory responses under flow through the
      immunocytochemical quantification of specific leukocyte adhesion molecules and
      determined that CD43, a cell adhesion molecule, was upregulated via flow exposure
      for leukocytes adherent to plasma-ePTFE, whereas basal levels of CD43 expression
      were not significantly altered on untreated ePTFE. When flow-exposed, adherent
      leukocytes were incubated in the presence of substrate immobilized anti-CD43
      immunoglobulin, the degree of cell displacement along flow was found to be
      significantly enhanced on plasma-ePTFE. Quantification of the cell population
      redistribution under flow using a modified random motility model, indicated that
      the incorporation of anti-CD43 on plasma-ePTFE led to a significant increase (243
      +/- 60%) in the cell dispersion coefficient, mu(D), whereas only a minimal
      increase (61 +/- 30%) was detected on non-adsorbed ePTFE. Overall, our results
      suggest that flow exposure can induce the migration of leukocytes adherent to
      prosthetic materials in a substrate-dependent manner. An important implication of
      our study is that, although biomaterials exposed to plasma intrinsically
      passivate leukocyte migration even under hemodynamic conditions, it may be
      possible to promote cell motility by targeting a specific, flow-responsive,
      adhesion molecule.

PMID- 11835155
TI  - Co-extrusion of biocompatible polymers for scaffolds with co-continuous
      morphology.
AB  - A methodology for the preparation of porous scaffolds for tissue engineering
      using co-extrusion is presented. Poly(epsilon-caprolactone) is blended with
      poly(ethylene oxide) in a twinscrew extruder to form a two-phase material with
      micron-sized domains. Selective dissolution of the poly(ethylene oxide) with
      water results in a porous material. A range of blend volume fractions results in
      co-continuous networks of polymer and void spaces. Annealing studies demonstrate
      that the characteristic pore size may be increased to larger than 100 microm. The
      mechanical properties of the scaffolds are characterized by a compressive modulus
      on the order of 1 MPa at low strains but displaying a marked strain-dependence.
      The results of osteoblast seeding suggest it is possible to use co-extrusion to
      prepare polymer scaffolds without the introduction of toxic contaminants. Polymer
      co-extrusion is amenable to both laboratory- and industrial-scale production of
      scaffolds for tissue engineering and only requires rheological characterization
      of the blend components. This method leads to scaffolds that have continuous void
      space and controlled characteristic length scales without the use of potentially
      toxic organic solvents.

PMID- 11835156
TI  - Effects of DMAEMA and 4-methoxyphenol on gingival fibroblast growth, metabolism,
      and response to interleukin-1.
AB  - Some components of resins used in restorative dentistry have been shown to alter
      metabolism in cultured oral epithelial cells. Here we have extended such studies
      to the underlying supportive tissue, composed of gingival fibroblasts (GF).
      Primary cultures of human GF were transferred to serum-free, defined medium and
      exposed to either 2-(dimethylamino)ethyl methacrylate (DMAEMA) or 4-methoxyphenol
      (MEHQ) for 24-72 h. At a DMAEMA concentration of 6.4 mM, which was well tolerated
      by epithelial cells, GF numbers, as estimated by crystal violet, and metabolic
      activity, as indicated by MTT, were reduced at least 60% within 24 h of exposure.
      Between 1.6 and 6.4 mM, there were dose-related reductions in cell numbers;
      however, at lower doses (0.32-0.64 mM), proliferation was stimulated. MEHQ,
      between 8 and 16 microM, did not stimulate cellular protein production. To
      examine the capacity of GF to respond to an inflammatory stimulus, interleukin-6
      (IL-6) production by confluent cells was estimated without or with these
      compounds. DMAEMA (1.6- 6.4 mM) virtually eliminated the acute IL-6 response of
      these cells to an interleukin-1beta challenge; only at 0.32 mM DMAEMA was the
      response restored. MEHQ (1.6-16 microM) reduced the IL-6 response by >50%. In
      summary, both growth and the innate immune responsivity of GF were affected by
      DMAEMA and MEHQ in vitro; thus, these compounds deserve careful evaluation for
      biocompatibility.

PMID- 11835157
TI  - Control of in vivo microvessel ingrowth by modulation of biomaterial local
      architecture and chemistry.
AB  - We developed a method for controlling local architecture and chemistry
      simultaneously in biomaterial implants to control microvessel ingrowth in vivo.
      Porous polypropylene disks (5 mm in diameter and 40 microm thick) were plasma
      coated with a fluoropolymer and then laser-drilled with 50-microm-diameter holes
      through their thickness. We then oxidized the disks to create hydroxyl
      functionality on the exposed polypropylene (inside the holes). Acrylamide was
      grafted to the hydroxyl groups through polymerization in the presence of
      activating ceric ions. Staining with toluidine blue O demonstrated that grafting
      occurred only inside the holes. We used the Hoffman degradation reaction to
      convert the amide groups of acrylamide to amine groups, and then we used ethylene
      glycol diglycidyl ether to attach biomolecules of interest inside the holes:
      secreted protein acidic and rich in cysteine (SPARC) peptide Lys-Gly-His-Lys
      (KGHK; angiogenic), thrombospondin-2 (TSP; antiangiogenic), or albumin (rat;
      neutral). In vivo testing in a rat subcutaneous dorsum model for a 3-week
      interval demonstrated a greater vessel surface area (p = 0.032) and a greater
      number of vessels (p = 0.043) in tissue local to the holes with KGHK-immobilized
      disks than with TSP-immobilized disks. However, differences between KGHK
      immobilized and albumin-immobilized disks were less significant (p = 0.120 and p
      = 0.289 for the vessel surface area and number of vessels, respectively). The
      developed methods have potential applications in biomaterial design applications
      for which selective neovascularization is desired.

PMID- 11835158
TI  - MMA/MPEOMA/VSA copolymer as a novel blood-compatible material: effect of PEO and
      negatively charged side chains on protein adsorption and platelet adhesion.
AB  - This study was designed to evaluate the effect of polyethylene oxide (PEO) and
      negatively charged side chains on blood compatibility. For this, novel copolymers
      (MMA/MPEOMA/VSA copolymers) with both PEO and negatively chargeable side chains
      were synthesized by random copolymerization of methyl methacrylate (MMA), methoxy
      PEO monomethacrylate (MPEOMA; PEO mol wt 1000), and vinyl sulfonic acid sodium
      salt (VSA) monomers of different compositions. MMA/MPEOMA copolymer (with PEO
      side chains) and MMA/VSA copolymer (with negatively chargeable side groups) also
      were synthesized for purposes of comparison. The synthesized copolymers were
      characterized by 1H-nuclear magnetic resonance spectroscopy and gel permeation
      chromatography. They were coated onto polyurethane (PU) or polymethyl
      methacrylate (PMMA) films by spin coating. The surface properties of
      MMA/MPEOMA/VSA copolymers were compared by water contact angle and zeta potential
      with those of MMA/MPEOMA and MMA/VSA copolymers of similar MPEOMA or VSA
      composition. Using electron spectroscopy for chemical analysis and scanning
      electron microscopy, respectively, the behaviors of the adsorption of blood
      proteins (albumin, gamma-globulin, fibrinogen, and plasma proteins) and the
      adhesion of platelets on the copolymer-coated surfaces also were compared. Among
      the copolymers, the MMA/MPEOMA/VSA copolymer with a monomer molar ratio 8:1:1 was
      observed to be particularly effective in preventing both protein adsorption and
      platelet adhesion on the surfaces, probably owing to the combined effects of
      highly mobile, hydrophilic PEO side chains and negatively charged side groups in
      aqueous solution.

PMID- 11835159
TI  - Biocompatibility of fluorinated polyimide.
AB  - Contact between blood and biomaterial triggers a complex series of events
      including protein adsorption, leukocyte adhesion and activation, and complement
      activation. In this article, a series of fluorinated polyimides cured at a
      different temperatures was prepared, and the biocompatibility of the membranes
      was evaluated using in vitro protein adsorption, neutrophil adhesion, and
      complement activation experiments under static conditions. We found that protein
      adsorption, neutrophil adhesion, and complement activation for the polyimides
      significantly depends on the curing temperature and decreases with an increase in
      the temperature and that the polyimide has a good biocompatibility compared with
      poly(styrene) and polydimethylsiloxane. We concluded that the rearrangement of
      molecules such as CF(3), sulfone, and ketone at the outermost surface occurs
      because of curing, which induces an increase in the hydrophobicity and that the
      cured polyimide suppresses protein adsorption, neutrophil adhesion, and
      complement activation because of its high hydrophobicity and low surface free
      energy.

PMID- 11835160
TI  - Recombinant human bone morphogenetic protein-2 promotes osteogenesis within
      atelopeptide type I collagen solution by combination with rat cultured marrow
      cells.
AB  - We evaluated the combination effect of recombinant human bone morphogenetic
      protein-2 (rhBMP-2) and cultured rat bone marrow mesenchymal stem cells (MSCs) in
      atelopeptide type I collagen (AC) solution on osteogenesis in a diffusion chamber
      (DC) to develop a bone substitute having consistent osteogenic capability for
      clinical applications. The cultured MSCs were obtained by 10-day primary culture
      of fresh bone marrow cells of Fischer rats. We prepared three groups of DCs: AC
      solution with rhBMP-2, AC solution with cultured MSCs, and AC solution with rhBMP
      2 and cultured MSCs. The prepared combined solutions were injected into DCs,
      which were subcutaneously implanted into the backs of syngeneic rats. DCs were
      harvested after 2, 4, or 8 weeks and analyzed for bone-forming capability by
      determining histological and osteoblastic biochemical markers. De novo bone
      formation was observed both inside and outside of the membrane filter of DCs in
      the group of AC solution with rhBMP-2 and cultured MSCs. The alkaline phosphatase
      activity and osteocalcin content in the group of AC solution with rhBMP-2 and
      cultured MSCs were significantly higher than those in the group of AC solution
      with cultured MSCs at any time. These findings indicate that AC aqueous solution
      is a useful material not only as a carrier of rhBMP-2 but also as a cell
      anchorage for differentiation and proliferation of MSCs. Therefore, this study
      suggests that clinical repairs of bone defects are feasible using injectable AC
      solution with rhBMP-2 and cultured MSCs as a bone substitute.

PMID- 11835161
TI  - Effect of calcium phosphate coating crystallinity and implant surface roughness
      on differentiation of rat bone marrow cells.
AB  - In this study, we examined the effect of calcium phosphate (Ca-P) coating
      crystallinity and of surface roughness on growth and differentiation of
      osteogenic cells. Grit-blasted titanium substrates were provided with Ca-P
      coatings of different crystallinities. Rat bone marrow (RBM) cells were cultured
      on these substrates and on noncoated rough and smooth titanium substrates. After
      specific culture times, expression of osteogenic markers by the cells was
      studied. Cells cultured on crystalline coatings and on titanium substrates
      proliferate, express alkaline phosphatase, osteocalcin (OC), and show
      mineralization of the extracellular matrix. Rough titanium substrates only
      express low OC levels. Significantly higher OC levels were expressed on smooth
      titanium, and even higher levels on the crystalline Ca-P coating. No difference
      was found in calcification between smooth and rough titanium. The crystalline
      coating showed more calcification than the titanium substrates. When substrates
      without cells were incubated in medium, precipitation of calcium was found. On
      the titanium substrates, this precipitate disappeared after prolonged incubation.
      The precipitate on the crystalline coating was stable and increased with longer
      incubation times. On the amorphous coatings, no proliferation and differentiation
      of RBM cells were found. After longer culture periods, substrates showed
      extensive dissolution. Cells on the amorphous coatings did express high levels of
      prostaglandin E2. In contrast, prostaglandin E2 expression was low for the other
      substrates. We conclude that crystalline Ca-P coatings stimulate differentiation
      of RBM cells, to a higher extent than titanium substrates. Surface roughness only
      has a limited effect on phenotype expression of the cells. In contrast, thin
      amorphous coatings show negative effects on the growth and differentiation of
      cultured RBM cells.

PMID- 11835162
TI  - Interaction of bioactive glasses with peritoneal macrophages and monocytes in
      vitro.
AB  - Macrophage activation was analyzed following exposure to pure, crystalline alpha
      quartz powders, two bioactive gel-glass powders of different compositions, and a
      melt-derived glass, 45S5 Bioglass. The release of reactive oxygen metabolites
      (chemiluminescence test), modifications of cell morphology, the amount of tumor
      necrosis factor alpha (TNFalpha) secreted, and the amount of TNFalpha mRNA
      expression were evaluated. The 45S5 Bioglass powders elicited the highest
      chemiluminescence response while the two solgel glasses had a lower response with
      less of an oxidative burst difference between them. Particulate bioactive glasses
      are actively ingested by mouse peritoneal macrophages, and only the 58S solgel
      glass had a moderate toxic effect on the macrophages. Macrophage cell morphology
      showed increased size and cell spreading, consistent with the high level of
      cytokine secretion induced by 45S5 Bioglass. The 45S5 Bioglass powders led to an
      increased release of TNFalpha and expression of TNFalpha mRNA relative to
      unstimulated and control treated monocytes. Bioactive glasses (and particularly
      45S5 Bioglass) that in vivo induce rapid bone growth appear to activate an
      autocrine-like process in which the response evoked by the material (for example
      monocyte and macrophage activation with cytokine production) enhances subsequent
      interactions with cells in contact with the material.

PMID- 11835163
TI  - Cell adhesion peptides alter smooth muscle cell adhesion, proliferation,
      migration, and matrix protein synthesis on modified surfaces and in polymer
      scaffolds.
AB  - The effects of cell adhesion peptides (RGDS, KQAGDV, VAPG) on vascular smooth
      muscle cells grown on modified surfaces and in tissue-engineering scaffolds were
      examined. Cells were more strongly adhered to surfaces modified with adhesive
      ligands than to control surfaces (no ligand or a nonadhesive ligand). Cell
      migration was higher on surfaces with 0.2 nmol/cm(2) of adhesive ligand than on
      control surfaces, but it was lower on surfaces with 2.0 nmol/cm(2) of adhesive
      ligand than it was on control surfaces. Further, cell proliferation was lower on
      adhesive surfaces than it was on control surfaces, and it decreased as the ligand
      density increased. Similarly, in the peptide-grafted hydrogel scaffolds, cell
      proliferation was lower in scaffolds containing the adhesive peptides than it was
      in control scaffolds. After 7 days of culture, more collagen per cell was
      produced in control scaffolds than in scaffolds containing adhesive peptides. In
      addition, collagen production decreased in the scaffolds as the ligand
      concentration increased. While modification of a surface or scaffold material
      with adhesive ligands initially increases cell attachment, it may be necessary to
      optimize cell adhesion simultaneously with proliferation, migration, and matrix
      production.

PMID- 11835164
TI  - Heparin and non-heparin-like dextrans differentially modulate endothelial cell
      proliferation: in vitro evaluation with soluble and crosslinked polysaccharide
      matrices.
AB  - Proliferation of endothelial cells (ECs) is a cellular step of particular
      importance for implanted cardiovascular biomaterials. Heparin and some synthetic
      water-soluble non-anticoagulant polysaccharides derived from dextran and bearing
      anionic carboxymethyl and hydrophobic benzylamine groups were first investigated
      for their effects on EC proliferation in vitro. The results assessed by cell
      counting, 3H-thymidine uptake, and flow cytometry analysis, showed that the
      derivatized dextran-bearing hydrophobic groups stimulated the EC growth in the
      presence of serum, whereas native dextran or dextran-bearing anionic
      carboxymethyl groups were inactive and heparin was slightly inhibitory. Then, we
      showed that the derivatized dextran enhanced EC proliferation by potentiation of
      the mitogenic activities of vascular endothelial growth factor (VEGF) and basic
      fibroblast growth factor (FGF-2), two potent EC growth factors. In the presence
      of 2 nM of derivatized dextran, a 3-fold and 13-fold increase of 3H-thymidine
      uptake was obtained with VEGF and FGF-2, respectively. Finally, proliferation of
      ECs was investigated on crosslinked gels made of polysaccharides. It is of
      interest that EC proliferation was higher on gels containing the derivatized
      dextran than on plain hydrogels, and heparinized gels inhibited cell
      proliferation. From the obtained results, we propose that the synthetic non
      heparin-like dextran may be of interest as a coating for the endothelialization
      of cardiovascular biomaterials.

PMID- 11835165
TI  - Influence of bioresorbable, unsintered hydroxyapatite/poly-L-lactide composite
      films on spinal cord, nerve roots, and epidural space.
AB  - The effect of forged unsintered hydroxyapatite/poly-L-lactide (u-HA/PLLA)
      composite films on spinal cord and nerve roots and its degradation behavior and
      osteoconductivity in epidural space were compared with those of calcined HA (c
      HA)/PLLA and unfilled PLLA films. Partial laminectomy was performed on 20
      rabbits, and u-HA/PLLA and PLLA films were implanted in the intervertebral space.
      Total laminectomy was performed on 30 rabbits to implant u-HA/PLLA, c-HA/PLLA,
      and PLLA films in both epidural and subcutaneous spaces. For up to 50 weeks,
      there were no histological changes in the spinal cord or nerve root, and no
      inflammatory cell infiltration into the epidural space around the films. The rate
      of decrease in viscosity average molecular weight of both composite films was
      initially higher than that of PLLA but eventually became lower, although there
      was no difference in the degradation behavior of the three films in either the
      epidural or subcutaneous spaces after 50 weeks. Scanning electron microscopic and
      energy-dispersive X-ray analysis indicated calcium phosphate deposits on the
      surface of composite films with new bone formation from 4 weeks. The u-HA/PLLA
      composite film therefore has good biocompatibility, osteoconductivity, and fast
      primary degradation rate, which may prove compatible with application to spinal
      surgery.

PMID- 11835166
TI  - Electrically communicating three-dimensional cardiac tissue mimic fabricated by
      layered cultured cardiomyocyte sheets.
AB  - Recent progress in stem cell biology is likely to provide implantable sources of
      human cardiomyocytes in the near future. This possibility has encouraged cardiac
      tissue engineering. To construct heart-like tissue, we have exploited the
      capabilities of novel cell culture surfaces grafted with a temperature-responsive
      polymer, poly(N-isopropylacrylamide) (PIPAAm), to produce intact viable monolayer
      cell sheets simply by reducing culture temperature. Cultured chick embryonic
      cardiomyocyte sheets detached from PIPAAm-grafted surfaces were layered into
      tissue-like laminate stacks using hydrophilic support and transfer membranes. The
      layered cell sheets rapidly adhered to each other, establishing cell-to-cell
      connections characteristic of heart tissue, including desmosomes and intercalated
      disks. Bilayer cell sheets pulsed spontaneously and synchronously, altering their
      characteristic pulsing frequency with applied electric stimulation transmitted
      across the sheets. These results demonstrate that electrically communicative
      three-dimensional cardiac constructs can be achieved by stacking monolayer
      cardiomyocyte sheets. Cardiac tissue engineering based on this technology will
      facilitate new in vitro heart models and may prove useful for in vivo
      cardiovascular tissue repair.

PMID- 11835167
TI  - Transverse process fusion with bovine anorganic bone.
AB  - A biodegradable collagen membrane and bovine anorganic bone were studied in a
      rabbit spine fusion model. The bovine, anorganic bone is a nonantigenic,
      acellular clinical product used as a bone substitute for dento-alveolar
      applications. We reasoned this product with a collagen membrane could be useful
      for spine fusions. Our hypothesis was that bovine, anorganic bone, and a collagen
      membrane would promote spine fusion equivalent to an autogenous bone graft. To
      test the hypothesis, the transverse processes of the fourth and fifth lumbar
      vertebrae were decorticated in 30 rabbits divided equally among five groups. In
      one group, following decortication, no treatment was administered, whereas in the
      remaining four groups, treatments consisted of either autograft, collagen
      membrane, anorganic bone, or anorganic bone plus collagen membrane. Rabbits were
      euthanized 6 weeks after surgery, and the lumbar vertebrae were removed,
      radiographed, and processed for histology. The radiographs and histological
      sections were subjected to quantitative morphometric analyses and post hoc
      statistical testing (p < or = 0.05). We determined anorganic bone without a
      collagen membrane migrated into the soft tissues contiguous to the transverse
      processes. However, with a collagen membrane, the anorganic bone remained at the
      implant site, causing an osseous fusion of the transverse processes. Although the
      autograft promoted the greatest amount of new bone formation, significant
      transverse process fusion was accomplished with the anorganic bone and collagen
      membrane. Additional longer term studies are contemplated to validate feasibility
      of this clinical option, including a biomechanical component.

PMID- 11835168
TI  - Engineering protein and cell adhesivity using PEO-terminated triblock polymers.
AB  - Previous studies on customizing cell culture environments have utilized a variety
      of microfabrication-based tools to control the spatial localization of adhesive
      proteins and subsequently mammalian cells. Others have used various methods to
      immobilize nonadhesive PEO-based polymers on surfaces to inhibit protein
      absorption and cell adhesion. In this study, we report the application of a well
      characterized, commercially available, PEO-terminated triblock polymer (Pluronic
      F108) to create micropatterned nonadhesive domains on a variety of biomaterials
      that deter cell adhesion for up to 4 weeks in culture. The Pluronic can be
      applied using microfluidic tools or photolithographic techniques, and can be
      adsorbed to a variety of common surfaces including tissue culture polystyrene,
      methylated glass, silicone, and polylactic-co-glycolic acid. The effectiveness of
      the Pluronic in inhibiting cell adhesion in the presence of collagen I is also
      quantified. Finally, these patterning techniques are generalized to control
      tissue organization on a variety of common biomaterials. This simple method for
      micropatterning PEO and, therefore, proteins and cells should prove useful as a
      tool for biomolecular surface engineering.

PMID- 11835169
TI  - Fluorinated surface-modifying macromolecules: modulating adhesive protein and
      platelet interactions on a polyether-urethane.
AB  - Polyether-urethanes (PEUs) have been the materials of choice for the manufacture
      of conventional blood-contacting devices. Nevertheless, biostability and blood
      compatibility are still among the principal limitations in their long-term
      application. Studies investigating the development of protective coatings for
      PEUs have shown that degradation can be reduced with the use of fluorinated
      surface-modifying macromolecules (SMMs). It has also been hypothesized that SMM
      modified PEU surfaces may exhibit improved blood compatibility because other
      studies have shown a modulation in fibrinogen adsorption onto these surfaces. To
      determine the blood compatibility of a PEU-containing fluorinated SMMs, a series
      of in vitro experiments were designed to study the pattern of protein adsorption
      from plasma and then to assess the nature of platelet adhesion and activation on
      each substrate. Western blot analysis as well as single protein studies revealed
      that the dominant "adhesive proteins" [fibrinogen (Fg), fibronectin (Fnc), and
      vitronectin (Vnc)] were adsorbed on two of the SMM-containing PEUs in lower
      amounts relative to unmodified base. Platelet adhesion and activation data
      further highlighted the differences among the various substrates. It was shown
      that the unmodified base had a higher number of adhered platelets relative to the
      SMM-modified surfaces, and that of the SMM-containing substrates, which showed
      the lowest levels of adhesive proteins also, exhibited significantly lower
      platelet densities. Close morphological examination further revealed that
      platelets residing on these latter substrates were not appreciably activated.
      Based on the current evidence, it is believed that the fluorinated SMMs
      demonstrate good potential for the development of surfaces with minimal
      thrombogenic character in in vivo applications.

PMID- 11835170
TI  - Shear stress and material surface effects on adherent human monocyte apoptosis.
AB  - Monocytes play a critical role as both phagocytes and mediators of inflammatory
      responses in the prevention of cardiovascular device-related infections. However,
      persistent infection of these devices still occurs and may be attributed to
      deleterious cellular alterations resulting from monocyte interactions with a
      foreign material in an environment of dynamic flow. Thus, the effects of both
      shear stress and adhesion to material surfaces on human monocyte apoptosis were
      investigated. A rotating disk system generated physiologically relevant shear
      stress levels (0-14 dyn/cm(2)), and shear-related apoptosis occurring in adherent
      monocytes was characterized. Using annexin V analysis, apoptosis of polyurethane
      adherent monocytes under shear for 4 h increased to levels >70% with increasing
      shear in a near-linear fashion (r2 = 0.713). It was qualitatively confirmed using
      confocal microscopy that filamentous (F)-actin distribution was altered, that DNA
      fragmentation occurred, and that activated caspases were involved in shear
      induced apoptosis. Static studies determined that spontaneous apoptosis was
      material-dependent over 72 h by demonstrating marked differences between
      apoptosis of monocytes adherent to a polyurethane compared to an alkyl-modified
      glass. Treatment with TNF-alpha augmented this material dependency in a dose
      dependent fashion over time. F-actin content of TNF-alpha-treated cells decreased
      to <62% of untreated cells. We conclude that concomitant effects from both
      material surfaces and dynamic flow mediate human monocyte apoptosis and may have
      serious implications in the context of implanted cardiovascular device infection.

PMID- 11835171
TI  - Hydroxyapatite ceramic bodies with tailored mechanical properties for different
      applications.
AB  - A perfect control on the final ceramic features will enable the research/clinical
      community to spread the use of calcium phosphate ceramic bodies to a large number
      of applications and/or requirements. The mechanical properties of hydroxyapatite
      ceramic bodies manufactured by different techniques and with different porosities
      is presented. The flexural strength, hardness, fracture toughness, surface
      roughness, and their evolution after immersion in SBF are studied. An increase of
      the mechanical properties with density is observed. The factors governing these
      results are analyzed. The increase of the porosity percentage of the bodies
      results in an increase on the surface roughness. The degradation studies show
      that the HA ceramics keep their integrity and mechanical properties under
      physiological conditions during the soaking time studied. The OHAp ceramic bodies
      with controlled porosity could be appropriated for hard tissue substitution or as
      a carriers for controlled delivery of drugs or as scaffolds for tissue
      engineering.

PMID- 11835172
TI  - Shear force modulates osteoblast response to surface roughness.
AB  - Previous studies have shown that osteoblasts are sensitive to surface roughness.
      When cultured on Ti, MG63 osteoblast-like cells exhibit decreased proliferation
      and increased differentiation with increasing surface roughness. In vivo,
      osteoblasts also are subjected to shear force during osseointegration. To examine
      how shear force modulates osteoblast response to surface roughness, MG63 cells
      were cultured on glass disks or Ti disks with three different R(a) values and
      topographies (PT: R(a) = 0.60 microm; SLA: R(a) = 3.97 microm; TPS: R(a) = 5.21
      microm) in a continuous flow device, resulting in shear forces of 0, 1, 5, 14,
      and 30 dynes/cm(2). Confluent cultures were exposed to fluid flow for 1 h. After
      an additional 23 h, cell number, alkaline-phosphatase-specific activity, and
      levels of osteocalcin, TGF-beta1, and PGE2 in the conditioned media were
      determined. Cell numbers on smooth surfaces (glass and PT) were unaffected by
      shear force. In contrast, shear force caused a dose-dependent reversal of the
      decrease in cell numbers seen on rough SLA and TPS surfaces. Alkaline-phosphatase
      specific activity was unaffected on glass or PT, but shear force caused a
      biphasic reduction in the roughness-dependent increase on SLA and TPS that was
      maximal at 14 dynes/cm(2). There was a similar effect seen with TGF-beta1 levels.
      Osteocalcin was unaffected on smooth surfaces; shear force caused a dose
      dependent reduction in the roughness-stimulated increase seen on SLA and TPS.
      PGE2 production was increased by shear force on all surfaces. There was a twofold
      increase in PGE2 levels in the media of MG63 cells cultured on glass and PT in
      response to 14 dynes/cm(2), but on SLA and TPS, 14 dynes/cm(2) shear force caused
      a 9-10-fold increase. These results show that osteoblastic response to shear
      force is modulated by surface topography. The shear-force-mediated decrease in
      osteoblast differentiation seen in cultures on rough surfaces may be due to
      increased production of PGE2.

PMID- 11835173
TI  - Comparitive study of the formation of hydroxyapatite in simulated body fluid
      under static and flowing systems.
AB  - alpha-CaSiO3 ceramics of nominal composition CaO 46.0, SiO2 54.0, and Na2O 0.4
      mass% were soaked in simulated body fluid (SBF). The soaking systems were
      maintained under both static and flowing conditions to study their effect on the
      formation of hydroxyapatite (HAp). Two different flowing systems were designed
      for soaking, namely, a closed system using a fast flow rate of about 2.8 mL/s
      (circulating system) and an open system using a slow flow rate of about 40 mL/day
      (slow flowing system). The HAp layer in all samples initially formed as a rough
      layer of ball-like particles. Under a fast flow of SBF solution, silica gel
      particles peeled from silica-rich interlayer during the first soaking period. The
      silica gel particles then reattached to the product HAp layer and induced the
      formation of new HAp particles of smaller size. In the slow flowing system, the
      rough HAp layer initially formed on the ceramic surfaces became gradually
      smoother after prolonged soaking. The formation rate and thickness of the HAp
      layer decreased with increasing flow rate of the SBF solution. These results
      indicate that flowing SBF solution gives rise to differences in the formation
      rates, formation behavior, and microstructure of the HAp layer.

PMID- 11835174
TI  - Anticoagulant activity of sulfonated polyrotaxanes as blood-compatible materials.
AB  - Polyrotaxanes, in which alpha-cyclodextrins (alpha-CDs) are threaded onto
      poly(ethylene glycol)-b-poly(propylene glycol)-b-poly(ethylene glycol) triblock
      copolymers (Pluronic) capped with benzyloxycarbonyl(Z)-L-phenylalanine (Z-L-Phe),
      were prepared, and sulfopropyl groups were introduced to hydroxyl groups of alpha
      CDs in the polyrotaxanes. The supramolecular structure and the chemical
      composition of the polyrotaxanes after the sulfonation were confirmed by 1H-NMR,
      13C-NMR, and elemental analysis. Anticoagulant activity of the polyrotaxanes and
      sulfonated polyrotaxanes was measured by activated partial thromboplastin time
      (APTT). It was found that the polyrotaxanes and the sulfonated polyrotaxanes
      showed greater anticoagulant activity than Pluronic itself, suggesting that both
      the supramolecular structure of the polyrotaxanes and the sulfonated groups
      contribute to the inhibition of intrinsic coagulation factors. Finally, our
      designed polyrotaxanes are suggested to be a promising candidate when fabricating
      blood-compatible medical devices by blending with or coating on clinically used
      polymers.

PMID- 11835175
TI  - Compliant design of artificial graft: compliance determination by new digital X
      ray imaging system-based method.
AB  - The development of an artificial graft requires formulation of biomechanical
      design criteria. The compliance of artifical grafts, based on the intraluminal
      pressure-internal diameter (Pi-Di) relationship, was measured by a novel method
      using a digital X-ray imaging system coupled with an edge detection algorithm and
      a pressure transducer. The Pi-Di values were obtained from digital angiographic
      images under continuous inflation of a canine femoral artery anastomosed with an
      expanded poly(tetrafluoroethylene) (ePTFE) vascular graft as a model vessel with
      a pressurized contrast medium. The Di at Pi using an NIH Image software specially
      programmed for the entropy filter method, which enables the detection of the edge
      of the vessel phantoms of the images, was determined. The Pi-Di relationships
      showed a "J-shape" curve for the artery, a steeper line with a very low pressure
      dependent distensibility for the ePTFE graft, and an intermediate curve for the
      anastomosis protion. The two indices for the vessel compliance, the stiffness
      parameter (beta value) and the diameter compliance (Cd), both of which were
      calculated from the Pi-Di relationships, were 10.6 and 6.8%/mmHg x 10(-2) for the
      artery, 164 and 0.51%/mmHg x 10(-2) for the ePTFE, and 14.4 and 5.5%/mmHg x 10(
      2) for the anastomosis portion, respectively. This method can measure compliance
      at any portions of the sampling vessel in a single experiment on a real-time
      basis with very high accuracy, compared with conventional methods, and even in
      cases of intimal thickening and/or connective tissues-adhered vessels, and may
      serve to provide information on compliant design criteria of artificial and
      tissue-engineered graft.

PMID- 11835176
TI  - Smooth muscle cell adhesion on crosslinked hyaluronan gels.
AB  - Hyaluronic acid (HA)-based polymers (hylans) are highly biocompatible and can be
      structurally modified to obtain desired mechanical properties. This study
      evaluated divinyl sulfone-crosslinked solid and particulate hylans as cellular
      scaffolds. These two hylan types differ in surface characteristics, mode of
      preparation, HA content, and extent of crosslinking. Neonatal rat aortic smooth
      muscle cells were cultured on hylan gels coated with matrix factors including
      collagen I, ECM gel, laminin, and fibronectin and on uncoated controls for < or
      =4 weeks. Cell attachment was sparse on uncoated controls but significantly
      enhanced on coated gels. Cell morphology was influenced by the identity of the
      matrix factors coated and the surface topography of the hylan gels. Cells
      attached to coated particulate gels appeared either highly spread (collagen,
      fibronectin) or irregularly shaped (ECM gel, laminin). Cells on laminin and
      fibronectin-coated solid gels were rounded and nonproliferative. Cells
      proliferated most rapidly on ECM gel-coated gels. The uneven surface of
      particulate gels induced more protein deposition and the subsequent attachment
      and active proliferation of cells. This study shows that surface texturizing and
      subsequent surface treatment with matrix factors enhances cell attachment and
      proliferation of hylans. These results are useful toward developing bioengineered
      materials based on cell-hylan composites.

PMID- 11835178
TI  - Enkephalinergic control of the secretory activity of neurons producing
      stereoisomers of crustacean hyperglycemic hormone in the eyestalk of the crayfish
      Orconectes limosus.
AB  - A subgroup of neurons in the classical X organ sinus gland neuroendocrine system
      of the crayfish (Orconectes limosus) eyestalk produces two chiral forms of the
      crustacean hyperglycemic hormone (CHH) in two different types of neurons: CHH in
      22 cells and D Phe(3) CHH in eight cells. Previous reports have demonstrated that
      release of CHH from the sinus gland is inhibited by enkephalins. Here, we have
      addressed the questions of 1) whether this inhibition affects one or both types
      of CHH neurons, 2) where the site of enkephalinergic control of CHH and/or D
      Phe(3) CHH is, and 3) whether the inhibitory effect is due to direct or indirect
      interactions of enkephalinergic neurons with CHH cells. In vitro incubations of
      neurosecretory complexes followed by immunoassays of CHH isoforms indicated that
      both methionine and leucine enkephalins inhibit release of the two CHH isoforms
      from crayfish eyestalks, by a receptor mediated process. Whole mount double or
      triple immunofluorescence labelings combined with confocal microscopy revealed
      enkephalin immunostaining in all neuropils of the eyestalk, except in the sinus
      gland. Virtual thin confocal sections showed many close appositions between
      terminals of enkephalinergic neurons and dendritic arborizations of specific CHH
      immunoreactive cells in the medulla terminalis neuropil. This provides the first
      evidence for direct inputs from enkephalinergic neurons into dendrites of both
      CHH cell types, which suggests that enkephalins inhibit release of both CHH
      isoforms via synaptic contacts.

PMID- 11835177
TI  - Prophylactic treatment of gram-positive and gram-negative abdominal implant
      infections using locally delivered polyclonal antibodies.
AB  - The increasing clinical incidence and host risk of biomaterial-centered
      infections, as well as the reduced effectiveness of clinically relevant
      antibiotics to treat such infections, provide compelling reasons to develop new
      approaches for treating implanted biomaterials in a surgical context. We describe
      the direct local delivery of polyclonal human antibodies to abdominal surgical
      implant sites to reduce infection severity and mortality in a lethal murine model
      of surgical implant-centered peritoneal infection. Surgical implant-centered
      peritonitis was produced in 180 female CF-1 mice by the direct inoculation of
      surgical-grade polypropylene mesh disks placed in the peritoneal cavity with
      lethal doses of either methicillin-resistant Staphylococcus aureus (MRSA) or
      Pseudomonas aeruginosa. Mice randomly received a resorbable antibody delivery
      vehicle at the implant site: either a blank carboxymethylcellulose (CMC) aqueous
      gel or the same CMC gel containing 10 mg of pooled polyclonal human
      immunoglobulin G locally on the implant after infection, either alone or in
      combination with systemic doses of cefazolin or vancomycin antibiotics. Human
      antibodies were rapidly released (first-order kinetics) from the gel carrier to
      both peritoneal fluids and serum in both infection scenarios. Inocula required
      for lethal infection were substantially reduced by surgery and the presence of
      the implant versus a closed lethal peritonitis model. Survival to 10 days with
      two different gram-negative P. aeruginosa strains was significantly enhanced (p <
      0.01) by the direct application of CMC gel containing antibodies alone to the
      surgical implant site. Human-equivalent doses of systemic vancomycin provided a
      significantly improved benefit (p < 0.01) against lethal, implant-centered, gram
      positive MRSA infection. However, locally delivered polyclonal human antibodies
      in combination with a range of systemic vancomycin doses against MRSA failed to
      improve host survival. Successful antibody therapy against gram-negative, implant
      centered infections complements the clinically routine use of systemic
      antibiotics, providing a mechanism of protection independent of antibiotic
      resistance.

PMID- 11835179
TI  - Visceral region in the rat primary somatosensory cortex identified by vagal
      evoked potential.
AB  - Recent noninvasive human studies have reconfirmed the presence of a viscerally
      responsive region in the most lateral part of the primary somatosensory cortex
      (S1). The present electrophysiological study identified the corresponding area in
      rats as a vagal afferent projection region and examined the cytoarchitecture.
      Electrical stimulation of the cervical vagus nerve elicited a field potential
      comparable in waveform, latency, and amplitude to the simultaneously evoked
      potential in the insular visceral sensory cortex. The potential field adjoined
      the S1 trigeminal region without overlap, and was rostroventral to the lip
      representation barrel field, which was identified histochemically, and
      rostrodorsal to the tongue representation region, which was identified
      electrophysiologically. The vagal potential underwent a phase reversal in the
      middle layers; thus, the current sink site was cytoarchitectonically identified
      as the most rostral part of the parietal granular cortex or the S1, where no
      somatosensory input has previously been demonstrated. The rat S1 contains a
      region representing general visceral information, topographically located as if
      the visceral organs protruded from the mouth.

PMID- 11835180
TI  - Neuronal development in larval chiton Ischnochiton hakodadensis (Mollusca:
      Polyplacophora).
AB  - Chitons are the most primitive molluscs and, thus, a matter of considerable
      interest for understanding both basic principles of molluscan neurogenesis and
      phylogeny. The development of the nervous system in trochophores of the chiton
      Ischnochiton hakodadensis from hatching to metamorphosis is described in detail
      by using confocal laser scanning microscopy and antibodies raised against
      serotonin, FMRFamide, and acetylated alpha tubulin. The earliest nervous elements
      detected were peripheral neurons located in the frontal hemisphere of
      posthatching trochophores and projecting into the apical organ. Among them, two
      pairs of unique large lateral cells appear to pioneer the pathways of developing
      adult nervous system. Chitons possess an apical organ that contains the largest
      number of neurons among all molluscan larvae investigated so far. Besides, many
      pretrochal neurons are situated outside the apical organ. The prototroch is not
      innervated by larval neurons. The first neurons of the developing adult central
      nervous system (CNS) appear later in the cerebral ganglion and pedal cords. None
      of the neurons of the larval nervous system are retained in the adult CNS. They
      cease to express their transmitter content and disintegrate after settlement.
      Although the adult CNS of chitons resembles that of polychaetes, their general
      scenario of neuronal development resembles that of advanced molluscs and differs
      from annelids. Thus, our data demonstrate the conservative pattern of molluscan
      neurogenesis and suggest independent origin of molluscan and annelid
      trochophores.

PMID- 11835181
TI  - Immunohistochemical localization of candidates for vesicular glutamate
      transporters in the rat brain.
AB  - Vesicular glutamate transporter 1 (VGluT1) is one of the best markers for
      glutamatergic neurons, because it accumulates transmitter glutamate into synaptic
      vesicles. Differentiation-associated Na(+)-dependent inorganic phosphate
      cotransporter (DNPI) shows 82% amino acid identity to VGluT1, and is another
      candidate for vesicular glutamate transporters. Here, we report the
      immunocytochemical localization of DNPI and compare it with that of VGluT1 in the
      adult rat brain. Both DNPI and VGluT1 immunoreactivities were found mostly in
      neuropil, presumably in axon terminals, throughout the brain. In the
      telencephalic regions, intense DNPI immunoreactivity was observed in the
      glomeruli of the olfactory bulb, layer IV of the neocortex, granular layer of the
      dentate gyrus, presubiculum, and postsubiculum. In contrast, VGluT1
      immunoreactivity was intense in the olfactory tubercle, layers I-III of the
      neocortex, piriform cortex, entorhinal cortex, hippocampus, dentate gyrus, and
      subiculum. In the thalamic nuclei, DNPI-immunoreactive terminal-like profiles
      were much larger than VGluT1-immunoreactive ones, suggesting that DNPI
      immunoreactivity was subcortical in origin. DNPI immunoreactivity was much more
      intense than VGluT1 immunoreactivity in many brainstem and spinal cord regions,
      except the pontine nuclei, interpeduncular nucleus, cochlear nuclei, and external
      cuneate nucleus. In the molecular layer of the cerebellar cortex, climbing-like
      fibers showed intense DNPI immunoreactivity, whereas neuropil contained dense
      VGluT1-immnoreactive deposits. Both DNPI and VGluT1 immunoreactivities were
      observed as mossy fiber terminal-like profiles in the cerebellar granular layer.
      DNPI and VGluT1 immunoreactivities appeared associated with synaptic vesicles in
      the axon terminals forming asymmetric synapses in several regions examined
      electron microscopically. The present results indicate that DNPI and VGluT1 are
      used by different neural components in most, if not all, brain regions,
      suggesting the complementary functions of DNPI and VGluT1.

PMID- 11835182
TI  - Seasonal changes in the densities of alpha(2) noradrenergic receptors are
      inversely related to changes in testosterone and the volumes of song control
      nuclei in male European starlings.
AB  - The functions of song and the contextual cues that elicit song change seasonally
      in parallel with testosterone (T) concentrations in male European starlings. T is
      high in spring when at least one function of male song is that of immediate mate
      attraction, and low outside the context of breeding, when starlings primarily use
      song for dominance or flock maintenance. Several brain nuclei that control song
      contain high densities of alpha(2)adrenergic receptors. T can regulate the
      density of alpha(2)adrenergic receptors in the avian brain, indicating that the
      density of alpha(2) adrenergic receptors within the song system might change
      seasonally. Although the function of seasonal brain variation is not entirely
      clear, in many songbirds the volumes of song nuclei are largest when T is high
      and males sing most. Male starlings, however, sing both when T is high and when T
      is low. Therefore, exploring seasonal changes in T and the volumes of song nuclei
      could provide insight into the function of these changes. The present study was
      performed to explore the relationships among T, the volumes of song nuclei, and
      the densities of alpha(2) adrenergic receptors within the song system of male
      starlings. Song nuclei (the high vocal center [HVc], robust nucleus of the
      archistriatum [RA], and Area X) were largest, T was highest, and the density of
      alpha(2) adrenergic receptors (within HVc and RA) was lowest during the breeding
      season. The reverse pattern was observed outside of the breeding season. These
      results suggest that changes in T, volumes of song nuclei, and alpha(2) receptor
      densities might regulate seasonal changes in song behavior or the context that
      will elicit song in male starlings.

PMID- 11835183
TI  - Projections of the posterodorsal preoptic nucleus and the lateral part of the
      posterodorsal medial amygdala in male gerbils, with emphasis on cells activated
      with ejaculation.
AB  - The posterodorsal preoptic nucleus (PdPN) and the lateral part of the
      posterodorsal medial amygdala (MeApd) express Fos with ejaculation in male
      gerbils. Ejaculation-activated cells participate in the PdPN and MeApd
      projections to each other and to the sexually dimorphic preoptic area (SDA), but
      those projections involve less than 20% of the activated PdPN cells and less than
      50% of the activated MeApd cells. To identify other potential targets of
      ejaculation-activated cells, we traced PdPN and lateral MeApd outputs using
      biotinylated dextran amine. The principal part of the bed nucleus of the stria
      terminalis (BSTpr) and the anteroventral periventricular nucleus (AVPv) were
      labeled from both sites and were injected with Fluoro-Gold to determine whether
      PdPN and lateral MeApd cells that express Fos with ejaculation would be
      retrogradely labeled. Fluoro-Gold was also applied to the dorsomedial
      hypothalamus (DMH) and retrorubral field (RRF) because such injections label PdPN
      cells in rats. The PdPN-DMH projection is minimal in gerbils, involving few, if
      any, ejaculation-related cells. Ejaculation-activated PdPN cells project to the
      AVPv (43%), dorsal BSTpr (30%), and RRF (12%). Those in the lateral MeApd project
      to the dorsal BSTpr (43%) and AVPv (18%). When these percentages are combined
      with those for ejaculation-activated cells involved in the PdPN and lateral MeApd
      projections to each other and to the medial SDA, the totals reach 100%. Thus,
      every PdPN and MeApd cell activated with ejaculation may participate in one of
      these projections. Similar projections may contribute to the similar behavioral
      effects of the PdPN and MeApd.

PMID- 11835184
TI  - Metathoracic neurons integrating intersegmental sensory information in the
      locust.
AB  - This paper describes the morphology and physiology of five types of local
      interneurons and three types of ascending intersegmental interneurons in the
      locust metathoracic ganglion that are points of convergence of sensory
      information from the wings. Four types of spiking local interneurons are members
      of a population with somata at the ventral midline. They are depolarised by
      stimulation of a metathoracic wing nerve, suggesting that they encode a sensory
      representation of this appendage. Some are also depolarised with short latencies
      following stimulation of a mesothoracic wing nerve, indicating that they collate
      intersegmental as well as local information. All the local interneurons have
      branches in the anterior ventral association centre or around the roots of the
      nerve that carries wing sensory neurons. This distinguishes them from other
      interneurons in the population. A fifth type of local interneuron that has
      unusual bilateral branching and is not a member of this population is described
      for the first time. The ascending interneurons are members of three populations.
      Neurons of each population have a characteristic pattern of responses to
      stimulation of the mesothoracic or metathoracic wing nerves, and some respond to
      tactile stimulation or movements of a hind leg. These latter interneurons thus
      collate information from both wings and legs. All three types of intersegmental
      interneurons have branches in the anterior ventral association centre or around
      the roots of the wing nerve. The responses of the interneurons described here
      shed new light on both local and intersegmental network function in this model
      system.

PMID- 11835185
TI  - Ascending and descending projections of the lateral vestibular nucleus in the
      frog Rana esculenta.
AB  - The lectin Phaseolus vulgaris leucoagglutinin was injected into the frog lateral
      vestibular nucleus (LVN) to study its antero- and retrograde projections. The
      following new observations were made. 1) In the diencephalon, vestibular
      efferents innervate the thalamus in a manner similar to that of mammalian
      species. The projections show a preference for the anterior, central, and
      ventromedial thalamic nuclei. 2) In the mesencephalon, vestibular fibers
      terminate in the tegmental nuclei and the nucleus of medial longitudinal
      fascicle. 3) In the rhombencephalon, commissural and internuclear projections
      interconnect the vestibular nuclei. Some of the termination areas in the
      reticular formation can be homologized with the mammalian inferior olive and the
      nucleus prepositus hypoglossi. Another part of the vestibuloreticular projection
      may transmit vestibular impulses toward the vegetative centers of the brainstem.
      A relatively weak projection is detected in the spinal nucleus of the trigeminal
      nerve, dorsal column nuclei, and nucleus of the solitary tract. 4) In the spinal
      cord, vestibular terminals are most numerous in the ipsilateral ventral horn and
      in the triangular area of the dorsal horn. 5) The coincidence of retrogradely
      labeled cells with vestibular receptive areas suggests reciprocal
      interconnections between these structures and the LVN. 6) In seven places, the
      LVN projections overlap the receptive areas of proprioceptive fibers, suggesting
      a convergence of sensory modalities involved in the sense of balance.

PMID- 11835186
TI  - Several subpopulations of neuropeptide Y-containing neurons exist in the
      infundibular nucleus of sheep: an immunohistochemical study of animals on
      different diets.
AB  - Conversely to rodents, the involvement of hypothalamic neuropeptide Y (NPY)
      neurons in the control of nutrition is poorly understood in ruminants such as
      sheep. Therefore, the aim of this work was to describe the NPY neurons of the
      diencephalon in ewes submitted to different diets. In colchicine-treated animals,
      large populations of NPY-immunoreactive (-ir) neurons were observed in a ventral
      and a lateral subpopulation of the infundibular nucleus (IN), in the median
      eminence, the pituitary stalk, and the dorsomedian and dorsocaudal nuclei. No
      labeled perikaryon was observed in the magnocellular neurons of the hypothalamus,
      although numerous labeled fibers were noted in the neural part of the pituitary.
      The pattern of distribution of NPY-ir neurons in the sheep hypothalamus is
      similar in many ways to those of rodents, but it presents also many specific
      characteristics that have not been previously described. In ewes that were fasted
      for 24 hours, or fed ad libitum, the number of NPY-ir neurons was the same
      whatever the hypothalamic structures. In underfed ewes (40% of maintenance for 24
      weeks), the lateral subpopulation of the IN presented a higher number of NPY-ir
      neurons than observed in the 100% fed ewes. Conversely, in the ventral
      subpopulation, the animals refed ad libitum (at least 150% of maintenance for 4
      days) presented a lower number of NPY-ir neurons than the other groups. The other
      NPY neuronal populations of the hypothalamus were not significantly modified by
      the dietary treatments. For the first time, we demonstrated the presence of two
      functionally distinct subpopulations of NPY neurons in the sheep IN. The
      variations of labeled neurons were correlated with plasma nonesterified fatty
      acid levels but not with leptinemia.

PMID- 11835187
TI  - Cortical projections to the nucleus of the optic tract and dorsal terminal
      nucleus and to the dorsolateral pontine nucleus in macaques: a dual retrograde
      tracing study.
AB  - The nucleus of the optic tract and dorsal terminal nucleus of the accessory optic
      system (NOT-DTN) along with the dorsolateral pontine nucleus (DLPN) have been
      shown to play a role in controlling slow eye movements and in maintaining stable
      vision during head movements. Both nuclei are known to receive cortical input
      from striate and extrastriate cortex. To determine to what degree this cortical
      input arises from the same areas and potentially from the same individual
      neurons, we placed different retrograde tracers into the NOT-DTN and the DLPN. In
      the ipsilateral cortical hemisphere the two projections mainly overlapped in the
      posterior part of the superior temporal sulcus (STS) comprising the middle
      temporal area (MT), the middle superior temporal area (MST), and the visual area
      in the fundus of the STS (FST) and the surrounding cortex. In these areas,
      neurons projecting to the NOT-DTN or the DLPN were closely intermingled.
      Nevertheless, only 3-11% of the labeled neurons in MT and MST were double-labeled
      in our various cases. These results indicate that the cortical input to the NOT
      DTN and DLPN arises from largely separate neuronal subpopulations in the motion
      sensitive areas in the posterior STS. Only a small percentage of the projection
      neurons bifurcate to supply both targets. These findings are discussed in
      relation to the optokinetic and the smooth pursuit system.

PMID- 11835188
TI  - Compartmentation of the rabbit cerebellar cortex.
AB  - The cytoarchitecture of the adult rabbit cerebellum is revealed by using zebrin
      II/aldolase c immunocytochemistry in both wholemount and sectioned material.
      Zebrin II is expressed by approximately half of the Purkinje cells of the
      cerebellar cortex. In most regions these form a symmetrical array of zebrin II
      positive and negative parasagittal bands. Four transverse expression domains are
      identified in the vermis: (1) an anterior zone, comprising four narrow bands, one
      at the midline and three laterally to either side, extending throughout the
      anterior lobe to the primary fissure; (2) a central zone with broad
      immunoreactive bands separated by narrow zebrin II negative bands that disappear
      caudally to leave no apparent compartmentation; (3) a posterior zone with
      prominent alternating zebrin II positive and negative bands; and (4) a nodular
      zone in which all Purkinje cells express zebrin II. In the hemispheres a striped
      topography is found in lobules HVI, HVII, and crus I, and all Purkinje cells are
      zebrin II+ in the flocculus and paraflocculus. Because of its importance for the
      classical conditioning of the eyeblink response, we made a detailed analysis of
      lobule HVI of the hemisphere. The immunocytochemical data show a complex
      substructure within HVI with three prominent zebrin II positive bands (probably
      homologous with P4a+, P4b+, and P5+ of rodents) separated by two zebrin II
      negative regions (P4- and P4b-). Thus, the organization of the rabbit cerebellum
      is consistent with the patterns described previously for rat, mouse, and opossum
      and suggests that there may be a common ground plan for the mammalian cerebellum.

PMID- 11835189
TI  - Metallothionein 1+2 protect the CNS during neuroglial degeneration induced by 6
      aminonicotinamide.
AB  - 6-Aminonicotinamide (6-AN) is a niacin antagonist, which leads to degeneration of
      gray matter astrocytes. Metallothionein 1+2 (MT-1+2) are neuroprotective factors
      in the central nervous system (CNS), and to determine the roles for MT after 6
      AN, we have examined transgenic mice overexpressing MT-1 (TgMTI* mice) after an
      i.p. injection with 6-AN. In control mice injected with 6-AN, astrocytes in
      specific gray matter areas of the brainstem showed degeneration. Reactive
      astrocytes surrounded the degenerated areas, which were heavily infiltrated by
      macrophages and T lymphocytes. MT-1+2 expression was significantly decreased in
      the damaged brainstem areas, but it increased in reactive astrocytes surrounding
      these areas and also in infiltrating macrophages. The levels of oxidative stress,
      as determined by immunoreactivity for inducible nitric-oxide synthase (iNOS),
      malondialdehyde (MDA), and nitrotyrosine (NITT), and the number of terminal
      deoxynucleotidyl transferase [TdT]-mediated deoxyuridine triphosphate [dUTP]
      digoxigenin nick end labeling-positive (TUNEL+), caspase-3+ apoptotic cells were
      significantly increased in the brainstem of normal mice after 6-AN. In the TgMTI*
      mice, the 6-AN-induced tissue damage was decreased in comparison to control mice,
      and they showed significantly reduced numbers of recruited macrophages and T
      lymphocytes, and a drastic reduction of oxidative stress and apoptotic cell
      death. In addition, the accompanying reactive astrogliosis was increased in the
      transgenic mice. To further study the potential protective role of MT, we
      administered intraperitoneally Zn-MT-2 to 6-AN-injected normal mice and found
      essentially the same results as those obtained in TgMTI* mice. Thus, we hereby
      report that endogenous MT-1 overexpression and exogenous MT-2 treatment have
      significant neuroprotective roles during CNS pathological conditions.

PMID- 11835190
TI  - Stereoselective disposition of talinolol in man.
AB  - The disposition of the beta-blocking drug talinolol is controlled by P
      glycoprotein in man. Because talinolol is marketed as a racemate, we reevaluated
      the serum-concentration time profiles of talinolol of a previously published
      study with single intravenous (30 mg) and repeated oral talinolol (100 mg for 14
      days) before and after comedication of rifampicin (600 mg per day for 9 days) in
      eight male healthy volunteers (age 22-26 years, body weight 67-84 kg) with
      respect to differences in the kinetic profiles of the two enantiomers S(-)
      talinolol and R(+) talinolol. Additionally, the metabolism of talinolol in human
      liver microsomes was examined. After oral administration, S(-) talinolol was
      slightly less absorbed and faster eliminated than R(+) talinolol. The absolute
      bioavailabilty of the R(+) enantiomer of talinolol was slightly but significantly
      higher than of its S(-) enantiomer. Coadministration of rifampicin further
      intensified this difference in the disposition of R(+) and S(-) talinolol (p <
      0.05). Formation of 4-trans hydroxytalinolol was the major metabolic pathway in
      human liver microsomes. All Cl(int) values of S(-) were higher than of R(+)
      talinolol; 0.1 microM ketoconazole inhibited the formation of all metabolites. In
      conclusion, the stereoselectivity of talinolol disposition is of minor
      importance, and most likely caused by presystemic biotransformation via CYP3A4.
      The less active R(+) talinolol might be suitable for phenotyping P-glycoprotein
      expression in man.

PMID- 11835191
TI  - Investigation of nail permeation enhancement by chemical modification using water
      as a probe.
AB  - Our objective was to screen molecules that could interact with keratin in the
      human nail and thereby improve the topical penetration of actives into and
      through the nail plate. We used specialized Franz-type diffusion cells for our
      permeation experiments and water as a marker molecule. Aqueous/hydroalcoholic
      gels containing the enhancers were spiked with tritiated water and compared with
      a control (without enhancer). We computed the normalized water flux (defined as a
      product of flux and nail thickness) for each gel. We defined an enhancement
      factor for water as the ratio of the normalized water flux from a gel containing
      enhancer to that of the control. Our results indicate that the chemical structure
      of the modifier is most important in determining its ability to enhance
      penetration. The best enhancement effect was obtained using N-(2
      mercaptopropionyl) glycine, a mercaptan derivative of an amino acid, in
      combination with urea. The concentration of each chemical modifier was linearly
      related to normalized water flux and mercaptan levels were more important that
      urea levels in penetration enhancement. Barrier integrity of nails was
      compromised after treatment with effective chemical modifiers. Thus, we have
      developed a suitable technique to screen nail penetration enhancers using water
      as a probe.

PMID- 11835192
TI  - Photodegradation study of a new activator of the cystic fibrosis chloride
      channel, the 6-hydroxy-10-chlorobenzo[c]quinolizinium chloride (MPB-07).
AB  - The photodegradation of 6-hydroxy-10-chlorobenzo[c]quinolizinium chloride (MPB
      07), a new activator of the transmembrane conductance regulator chloride channel,
      was studied in aqueous solutions exposed to artificial daylight (2300 Lux
      intensity). Various conditions of pH, concentration, and temperature were used.
      MPB-07 concentration was determined at regular time intervals by reversed-phase
      HPLC. MPB-07 stability was also studied at pH 7.4 in the dark. Results showed
      that in all the conditions tested MPB-07 underwent rapid photodegradation,
      apparently following first-order kinetics. Rate constants were dependent on the
      initial MPB-07 concentration, temperature, and pH. At pH 7.4, and for
      concentrations from 1 to 125 microM, half-lives ranged from 0.681 +/- 0.047 to
      4.54 +/- 0.28 h. The Arrhenius plot was linear and activation energy was
      calculated to be 20.7 kJ x mol(-1). Analysis by chemical ionization-mass
      spectrometry showed that the chlorine atom of the MPB-07 molecule might be
      replaced by an OH group during the photodegradation process. In the dark, MPB-07
      in solutions at pH 7.4 was found to be stable over a 6-week period. In
      conclusion, MPB-07 is a highly photolabile molecule that should be carefully
      protected from light when used.

PMID- 11835193
TI  - Mixed-effects modeling of the interspecies pharmacokinetic scaling of
      oxytetracycline.
AB  - Differences in the disposition of certain drugs across mammalian species often
      arise because of their diverse physiology and anatomical characteristics. Factors
      such as body mass, brain weight, and maximum lifespan are related to the way that
      different species of mammals handle drugs. Drug disposition data can be scaled
      across species when chronological time is substituted by the appropriate measure
      of pharmacokinetic time. In this study, we developed allometric scaling models
      for oxytetracycline, using serum disposition data obtained from the Food Animal
      Residue Avoidance Databank. The data were modeled using the mixed-effects
      modeling approach. The models obtained were validated using disposition data on
      swine. Oxytetracycline scaled across species based on body weight and the best
      interspecies model adequately predicted the value of the pharmacokinetic
      parameters across species. The population approach allows one to estimate the
      allometric coefficients and exponents of the pharmacokinetic parameters to obtain
      a model that best fits the multi-species pooled concentration-time data.
      Furthermore, this approach allows decisions to be made based on the statistical
      significance of the parameter estimates and the adequacy of the models that are
      not possible with traditional approaches.

PMID- 11835194
TI  - Characterization of the thermal properties of microcrystalline cellulose by
      modulated temperature differential scanning calorimetry.
AB  - The purpose of this study was to characterize the thermal properties of
      microcrystalline cellulose (MCC) and to investigate the influence of water on
      these properties. Differential scanning calorimetry (DSC), modulated temperature
      differential scanning calorimetry (MTDSC), thermomechanical analysis (TMA), and
      scanning electron microscopy (SEM) were used to characterize MCC. Three
      reproducible step transitions were detected in the dry material at 132, 159, and
      184 degrees C; for these transitions the magnitude of the heat capacity change
      varied by a factor of two. Exposure of MCC to water lowers the transition
      temperature in a manner comparable to a glass transition. The effect of water was
      different for samples equilibrated to different atmospheric humidities versus
      water added by granulation. A change in the physical properties of MCC after
      granulation with high amounts of water was observed. In conclusion, it appears
      that MCC has glass transitions, which come in reproducible triplets, and these
      transitions are affected by the presence of water. Also, for the materials
      studied, the transition temperatures are not affected by particle size and pulp
      source.

PMID- 11835195
TI  - Prevention of bone loss in ovariectomized rats by pulsatile transdermal
      iontophoretic administration of human PTH(1-34).
AB  - Serum human parathyroid hormone (1-34)[hPTH(1-34)] levels and the anabolic effect
      of hPTH(1-34) were compared after administration using multiple pulses of
      iontophoresis or subcutaneous (sc) intermittent injections to ovariectomized
      (OVX) Sprague Dawley rats. Triple-pulse iontophoretic administration of hPTH(1
      34) (doses: 40-400 microg/patch), achieved by repeated 30-min applications of a
      0.1 mA/cm(2) current separated by 45-min rest intervals, produced three sharp
      peaks in the serum hPTH(1-34) level in response to application of the current.
      Each peak appeared at the end of the 30-min current application period and was
      proportional to the hPTH(1-34) dose. Compared with once-daily sc injections (7
      pulses/week), triple-pulses iontophoretic administered 3 times/week (9
      pulses/week) for 4 weeks produced dose-related increases in the bone mineral
      density (BMD) of the distal 1/3 femur. For the sc administration, the relative
      BMD values using the vehicle injection as a reference standard for 1, 5, and 25
      microg/kg/day were 104, 114, and 121%, respectively. For iontophoretic
      administration, the relative BMD values using the placebo patch as a reference
      standard for 40, 120, and 400 microg/patch were 104, 110, and 116%, respectively.
      The increase in the BMD plotted against the area under the hPTH(1-34) serum level
      time curve (AUC) over 1 week resulted in similar straight lines in the 9
      pulses/week iontophoretic administration and the 7 pulses/week sc administration
      groups. The estimated iontophoretic dose giving an equivalent BMD to once-daily
      sc administration at 5 microg/kg/day was 120 microg/patch. These findings
      strongly suggest that three iontophoretic pulses administered on alternate days
      will exert an anabolic effect equivalent to that of daily sc administration at
      doses giving the same weekly AUC. Furthermore, this method of administering
      hPTH(1-34) might enable self-medication, a useful advance in the treatment of
      osteoporosis.

PMID- 11835196
TI  - Improvement of solubility and oral bioavailability of a poorly water-soluble
      drug, TAS-301, by its melt-adsorption on a porous calcium silicate.
AB  - The aim of the present study was to improve the solubility and oral
      bioavailability of a poorly water-soluble drug, 3-bis(4-methoxyphenyl) methylene
      2-indolinone (TAS-301), by its melt-adsorption on a porous calcium silicate,
      Florite RE (FLR), without any solvents. The melt-adsorbed products were prepared
      by two methods: the small-scale batch method and the twin screw extruder method.
      The drug was melted and adsorbed on FLR (i.e., "melt-adsorption"), above its
      melting point. Crystallinity of the drug in the melt-adsorbed product was
      estimated by differential scanning calorimetry (DSC) and powder X-ray diffraction
      analysis. The dissolution test was conducted by the JP XIII paddle method. Oral
      absorption of the melt-adsorbed product was studied in fasted and fed dogs. The
      melt-adsorbed products prepared by the two methods were in powder forms. The drug
      existed in an amorphous state in the product and hardly recrystallized even after
      storing at a stressed condition (60 degrees C/80% RH for 3 days). The TAS-301
      dissolution rate from the melt-adsorbed product was markedly enhanced compared
      with drug crystals. The area under the plasma concentration-time curve (AUC) and
      peak concentration (C(max)) values of the drug after dosing the melt-adsorbed
      product were significantly greater than those after dosing the drug crystals. The
      solubility and bioavailability of TAS-301 were improved by its melt-adsorption on
      FLR. The present findings suggest melt-adsorption is a useful technique for
      improving solubility and bioavailability of poorly water-soluble drugs.

PMID- 11835198
TI  - Protein spray freeze drying. 2. Effect of formulation variables on particle size
      and stability.
AB  - Spray freeze drying produces protein particles suitable for microencapsulation
      into polymeric microspheres intended for sustained release. Accessibility of
      encapsulated protein particles to the microsphere surface increases as the
      protein particle size is increased. Thus, it is desirable that the encapsulated
      protein particle size be minimized to limit initial release. We have investigated
      the effect of formulation on spray freeze-dried bovine serum albumin (BSA) as a
      model protein. Atomization conditions were fixed such that in the absence of
      excipient, the particle size of the sonicated powder was submicron, and there was
      substantial protein degradation (loss of monomer). Addition of low concentrations
      of surfactants (up to the CMC) or mannitol (up to the point where it tended to
      crystallize upon dehydration) resulted in partial stabilization without impacting
      particle size. Trehalose was successful in stabilizing the protein; however,
      there was a marked increase in particle size at the highest levels tested.
      Ammonium sulfate provided partial stabilization, but also tended to form crystals
      and increase particle size. FTIR measurements showed a loss of native secondary
      structure upon spray freeze drying that was ameliorated by addition of trehalose.
      Other excipients did not prevent structural perturbations. In general,
      stabilization of spray freeze-dried BSA was related to lowering of the specific
      surface area in the powder. A balance must be achieved when spray freeze drying
      proteins intended for encapsulation in sustained-release systems.

PMID- 11835197
TI  - Long-acting forms of Sonic hedgehog with improved pharmacokinetic and
      pharmacodynamic properties are efficacious in a nerve injury model.
AB  - The therapeutic effects of the Sonic hedgehog (Shh) have been difficult to
      evaluate because of its relatively short serum half-life. To address this issue
      polyethylene glycol modification (PEGylation) was investigated as an approach to
      improve systemic exposure. Shh was PEGylated by a targeted approach using
      cysteines that were engineered into the protein by site-directed mutagenesis as
      the sites of attachment. Sixteen different versions of the protein containing
      one, two, three, or four sites of attachment were characterized. Two forms were
      selected for extensive testing in animals, Shh A192C, which provided a single
      site for PEGylation, and Shh A192C/N91C, which provided two sites. The PEGylated
      proteins were evaluated for reaction specificity by SDS-PAGE and peptide mapping,
      in vitro potency, pharmacokinetic and pharmacodynamic properties, and efficacy in
      a sciatic nerve injury model. Targeted PEGylation was highly selective for the
      engineered cysteines and had no deleterious effect on Shh function in vitro.
      Systemic clearance values in rats decreased from 117.4 mL/h/kg for unmodified Shh
      to 29.4 mL/h/kg for mono-PEGylated Shh A192C that was modified with 20 kDa PEG
      maleimide and to 2.5 mL/h/kg for di-PEGylated Shh A192C/N91C modified with 2, 20
      kDa PEG vinylsulfone adducts. Serum half-life increased from 1 h for unmodified
      Shh to 7.0 and 12.6 h for the mono- and di-PEGylated products. These changes in
      clearance and half-life resulted in higher serum levels of Shh in the PEG-Shh
      treated animals. In Ptc-LacZ knock-in mice expressing lacZ under regulation of
      the Shh receptor Patched, about a 10-fold lower dose of PEG-Shh was needed to
      induce beta-galactosidase than for the unmodified protein. Therapeutic treatment
      of mice with PEG-Shh enhanced the regeneration of injured sciatic nerves. These
      studies demonstrate that targeted PEGylation greatly alters the pharmacokinetic
      and pharmacodynamic properties of Shh, resulting in a form with improved
      pharmaceutical properties.

PMID- 11835199
TI  - Targeting of liposomes to melanoma cells with high levels of ICAM-1 expression
      through adhesive peptides from immunoglobulin domains.
AB  - The P(0) protein is an immunoglobulin [Ig] superfamily cell adhesion molecule
      from peripheral nerve myelin. Synthetic peptides derived from the P(0) protein
      and leukocyte function-associated antigen-1 (LFA-1) were investigated as
      potential ligands for targeting liposomes to intercellular adhesion molecule-1
      (ICAM-1) expressing melanoma cells. Three synthetic P(0) peptides and one LFA-1
      peptide were selected for linkage to liposome surfaces. P(0)-peptide-1, from the
      extracellular Ig-like domain, increased liposome binding to M21 (6.36-fold) and A
      375 (1.85-fold) cells compared to control blank liposomes, but did not increase
      liposome binding to MeM 50-10 cells. P(0)-peptide-3, from the basic intracellular
      domain, increased binding of liposomes to all three melanoma cell lines
      nonspecifically due to its high content of positively charged amino acids. LFA-1-
      and negative control arg-gly-asp (RGD)-peptides did not affect liposome binding
      to M21 cells. The extent of P(0)-peptide-1-liposome binding to human melanoma
      cell lines correlated with the level of cellular ICAM-1 expression (r(2) =
      0.868). P(0)-peptide-1-mediated targeting of liposomes might, therefore, prove
      useful in the development of drug delivery systems for treatment of ICAM-1
      expressing malignant melanomas.

PMID- 11835200
TI  - Simultaneous determination of unlabeled and carbon-13-labeled etoricoxib, a new
      cyclooxygenase-2 inhibitor, in human plasma using HPLC-MS/MS.
AB  - A method for the simultaneous determination of etoricoxib and its carbon-13
      analog ((13)C(6)-etoricoxib) from human plasma has been developed and used to
      support bioavailability studies. Plasma samples (0.5 mL) were extracted by using
      a 3M Empore 96-well plate (C(8)) and the resulting extracts were analyzed by
      using a PE-Sciex API-3000 HPLC-MS/MS with a heated nebulizer interface (500
      degrees C). The method was validated with two different calibration curve ranges,
      one for etoricoxib (5 to 2500 ng/mL) determined in the presence of lower
      concentrations of (13)C(6)-etoricoxib (0.5 to 250 ng/mL), and a second curve for
      the quantitation of similar concentrations of both etoricoxib and (13)C(6)
      etoricoxib (0.5 to 250 ng/mL). Extraction recoveries of etoricoxib, (13)C(6)
      etoricoxib, and a methylated internal standard were >70% over the range of
      concentrations included in both calibration curves. Intraday precision and
      accuracy for the quantitation of etoricoxib were 7.8% relative standard deviation
      (RSD) or less and within 3.4% respectively over the range of 5 to 2500 ng/mL, and
      10.8% RSD or less and within 4 % respectively over the range of 0.5 to 250 ng/mL.
      Within-batch precision and accuracy for the quantitation of (13)C(6)-etoricoxib
      over the range of 0.5 to 250 ng/mL were 8.3% RSD or less and within 2.3%,
      respectively. The validated assay was used in support of human clinical trials.

PMID- 11835201
TI  - Assessment of amorphous content by microcalorimetry.
AB  - The amorphous content of model drugs was evaluated by isotherm microcalorimetry.
      Two model drugs were employed; lactose as a hydrophilic one and erythromycin as a
      hydrophobic one. When amorphous lactose was loaded in a sample cell with a water
      vial, a sharp exothermic peak due to the crystallization was observed. When a
      mixture of the amorphous and the crystalline forms was loaded, the peak area of
      the exothermic heat flow was proportional to the amorphous content.
      Quantification could be done with much higher accuracy than by the X-ray powder
      diffraction method reported in earlier literature. When erythromycin was used as
      a model drug, the crystallization was not completed by water but by organic
      solvents, which can dissolve erythromycin. The most adequate solvent for
      erythromycin was acetonitrile, of which the suitability was elucidated in terms
      of solubility and vapor pressure. This is the first report in which the role of
      the vapor pressure on crystallization behavior is discussed. The time needed to
      obtain the crystallization peak was controlled by mixing acetonitrile with water.
      The strategy to obtain the crystallization peak by microcalorimetry, which
      enables quantification of the amorphous content with high accuracy, is discussed.

PMID- 11835202
TI  - Single-dose study to compare the pharmacokinetics of HFA flunisolide and CFC
      flunisolide.
AB  - The hydrofluoroalkane (HFA) formulation of the inhaled corticosteroid flunisolide
      is a modification of the original chlorofluorocarbon (CFC) formulation. HFA
      flunisolide replaces CFC with an HFA propellant and uses a built-in spacer in its
      pressurized metered-dose inhaler. The average HFA flunisolide particle size is
      1.2 microm compared with 3.8 microm for the CFC formulation. The smaller particle
      size improves lung targeting, allowing a reduction in the HFA flunisolide dose
      relative to CFC flunisolide while maintaining comparable efficacy. In a study of
      12 healthy men, pharmacokinetic parameters were determined after single doses of
      1000 microg CFC flunisolide delivered without a spacer, 340 microg HFA
      flunisolide delivered through a spacer, and 516 microg HFA flunisolide delivered
      without a spacer. A standard noncompartmental analysis of the concentration data
      was performed and mean (+/- S.D.) pharmacokinetic values were reported. Peak
      plasma concentrations (observed C(max)) were similar for the three treatments.
      Area under the curve up to the time corresponding to the last measurable
      concentration (AUC(0)(-)(tlast)) was similar for the CFC and HFA flunisolide,
      plus spacer groups (4.4 +/- 1.6 ng x h/mL and 5.0+/- 4.2 ng x h/mL,
      respectively); however, AUC(0)(-)(tlast) for the HFA flunisolide without spacer
      group was comparatively lower than for the CFC group (3.5 +/- 1.6 ng x h/mL).
      Observed C(max) and AUC(0)(-)(tlast) for 6 beta-OH flunisolide, the first-pass
      metabolite of flunisolide and an indicator of oropharyngeal deposition, were
      significantly higher in the CFC flunisolide group than in either HFA flunisolide
      group.

PMID- 11835203
TI  - Freeze-drying using vacuum-induced surface freezing.
AB  - A method of freezing during freeze-drying, which avoids undercooling of a
      solution and allows growth of large, dendritic ice crystals, was investigated.
      Aqueous solutions of mannitol, sucrose, or glycine were placed under a chamber
      vacuum of approximately 1 mbar at a shelf temperature of +10 degrees C. Under
      these conditions, the solutions exhibit surface freezing to form an ice layer of
      approximately 1-3 mm thickness. On releasing the vacuum and lowering the shelf
      temperature to below the freezing point of the ice in the solution, crystal
      growth occurs to yield large, chimney-like ice crystals. The duration of primary
      drying of a frozen cake--as measured by using inverse comparative pressure
      measurement--was up to 20% shorter than when using a "moderate" freezing
      procedure (2 K shelf temperature per min). With mannitol, however, the residual
      moisture content of the final dried product was higher than with moderate
      freezing, and with sucrose and glycine there was no difference. These findings
      are related to the structures of the dried cakes formed during freezing, as
      examined by light microscopy and wide-angle X-ray diffraction. The introduction
      of an annealing step (4 h at a shelf temperature slightly above the onset melting
      point of the ice in the frozen cake) combined with the vacuum-induced surface
      freezing procedure maintains the rapid primary drying and produces a low residual
      moisture (0.2%) for the freeze-dried mannitol solution.

PMID- 11835204
TI  - Investigations of the role of cavitation in low-frequency sonophoresis using
      acoustic spectroscopy.
AB  - Application of low-frequency ultrasound significantly enhances skin permeability.
      The enhancement of skin permeability is mediated by cavitation, oscillation, and
      collapse of gaseous cavities. In this article, we report detailed investigations
      of the occurrence of cavitation during low-frequency sonophoresis. Cavitation was
      monitored by recording pressure amplitudes of subharmonic emission and broadband
      noise at four different ultrasound frequencies in the range of 20-100 kHz and at
      various intensities in the range of 0-2.6 W/cm(2). Enhancement of skin
      conductivity, in the presence of sodium lauryl sulfate (SLS), was also measured
      under the same ultrasound conditions. Enhancement of skin conductivity correlated
      well with the amplitude of broadband noise, which suggests the role of transient
      cavitation in low-frequency sonophoresis. No correlation was found between the
      subharmonic pressure amplitude and conductivity enhancement.

PMID- 11835205
TI  - Differential scanning calorimetric studies of the thermal stability of plasmid
      DNA complexed with cationic lipids and polymers.
AB  - The thermal stabilities of supercoiled (SC) and linear/open circular (LIN/OC)
      forms of plasmid DNA when complexed with cationic lipids or cationic polymers
      used for cellular transfection were assessed using differential scanning
      calorimetry. Differences in the stability of SC DNA produced by the cationic
      lipids DOTAP (1,2-dioleoyltrimethyl ammoniumpropane chloride), DSTAP (1,2
      distearyltrimethyl ammoniumpropane chloride), and DDAB
      (dimethyldioctadecylammonium bromide) upon complexation suggest possible effects
      of headgroup structure on the stability of SC DNA and minimal effects of lipid
      acyl chain saturation/unsaturation. Complexation of DNA with the cationic
      polymers polyethylenimine (PEI) or poly-L-lysine (PLL) (but not poly-L-arginine)
      resulted in a decreased stability of SC DNA when the DNA was in charge excess,
      although all polymers stabilized SC DNA when the polymer was in charge excess.
      The effects of these cationic polymers on the stability of SC DNA can be
      explained by changes produced in the tertiary structure of SC DNA upon binding
      and may reflect the importance of the topological constraint of supercoiling upon
      the stability of the resulting complexes.

PMID- 11835206
TI  - Structural relationships, thermal properties, and physicochemical
      characterization of anhydrous and solvated crystalline forms of tetroxoprim.
AB  - Six distinct phases of the antibacterial tetroxoprim (TXP) have been isolated by
      recrystallization from various solvents. These comprise two polymorphs, forms I
      and II, and four solvates with the following solvents and TXP solvent
      stoichiometric ratios: chloroform (3:2), water (3:2), methanol (2:1), and ethanol
      (2:1). Thermal and infrared spectral data showed that forms I and II are
      enantiotropically related with form II being stable below the transition
      temperature of 118 degrees C and form I melting at 159 degrees C. The crystal
      structure of form I contains three crystallographically independent TXP molecules
      arranged in layers formed by extensive base pairing between the 2,4
      diaminopyrimidine rings. This species invariably results upon heating the
      solvates of TXP. Thermogravimetry and differential scanning calorimetry
      respectively showed one-step mass losses and progressively increasing desolvation
      temperatures for the solvates with chloroform, water, ethanol, and methanol. X
      ray diffraction studies revealed that the latter three solvates are
      isostructural, belonging to the class of "isolated site" solvates. Extensive base
      pairing maintains the common TXP crystalline framework. Thermal data for the
      desolvation of these phases are reconciled with the observed crystal packing
      features. Experimental and computed powder X-ray patterns for form I and the
      solvates with water, methanol, and ethanol are presented.

PMID- 11835207
TI  - A novel approach to the pulmonary delivery of liposomes in dry powder form to
      eliminate the deleterious effects of milling.
AB  - The effect of lyophilization and jet-milling on liposome integrity was
      investigated as a function of their ability to retain the encapsulated model drug
      on reconstitution of the dry products. The encapsulation efficiencies of the
      lyophilized and jet-milled formulations were determined at various concentrations
      of lactose. Lyophilization resulted in considerable leakage of the model drug at
      lower concentrations of lactose, and jet-milling further augmented the leakage
      for all the lyophilized formulations, with optimum retention obtained for
      formulations containing at least 10:1 molar ratio of lactose/lipid. In an attempt
      to overcome the deleterious effects of lyophilization and jet-milling, the
      feasibility of formulating phospholipid-based powders that result in spontaneous
      formation of liposomes in an aqueous environment has been investigated.
      Partitioning of three model drugs (viz., ciprofloxacin, CM3 peptide, and
      salbutamol sulfate) between the aqueous phase and spontaneously formed liposomes
      was determined in terms of encapsulation efficiency. The effects of several
      parameters, including lactose concentration, lipid composition, and lipid
      concentration on the encapsulation efficiency of these model drugs were
      investigated. The spontaneous formation of liposomes on dispersion of
      phospholipid-based powder formulations was further evidenced by freeze-fracture
      scanning electron microscopy. This novel approach for the delivery of liposomes
      in dry powder form appears promising because lyophilization is not involved and
      jet-milling of these powder formulations did not impact encapsulation efficiency.
      Jet-milled phospholipid-based powder formulations showed high encapsulation
      efficiencies of 96.2 +/- 1.4% for ciprofloxacin, 100% for CM3 peptide, and 45.3
      +/- 3.1% for salbutamol sulfate compared with a high amount of leakage (> 50%)
      observed due to jet-milling of lyophilized liposome formulations encapsulating
      ciprofloxacin.

PMID- 11835208
TI  - Cryogenic grinding of indomethacin polymorphs and solvates: assessment of
      amorphous phase formation and amorphous phase physical stability.
AB  - The effect of cryogenic grinding on five crystal forms of indomethacin (IMC) was
      investigated with particular interest in the formation of amorphous phase. Powder
      X-ray diffraction (PXRD) and differential scanning calorimetry (DSC) demonstrated
      that amorphous phase formation took place for all three polymorphs (gamma, alpha,
      and delta) and one solvate (IMC methanolate). In the latter case, a postgrinding
      drying stage was needed to remove desolvated methanol from the ground amorphous
      product because methanol destabilized amorphous IMC presumably via a plasticizing
      effect. The crystal structure of another solvate, IMC t-butanolate, was
      unaffected by grinding, indicating that amorphous phase formation on grinding
      does not occur in all cases. Ground amorphous materials possessed similar glass
      transition temperatures but significant differences in physical stability as
      assessed by both isothermal and nonisothermal crystallization. It is argued that
      physical factors, namely residual crystal phase and specific surface area,
      determine the isothermal and nonisothermal crystallization behavior of ground
      amorphous samples as opposed to intrinsic differences in the structure of the
      amorphous phase.

PMID- 11835209
TI  - Pharmacokinetic and pharmacodynamic evaluation of intermittent versus continuous
      alendronate administration in rats.
AB  - We studied the differences in pharmacokinetics and pharmacodynamics of the same
      dose of alendronate administered subcutaneously as intermittent bolus injection
      or continuous infusion in rats. Two rat models of bone disease were applied. Bone
      cancer was produced by intratibial inoculation of Walker carcinosarcoma cells,
      and a model of augmented bone resorption was produced by vitamin D(3) treatment
      of rats that had undergone thyroidparathyroidectomy. Higher amounts of
      alendronate were found in bones and in internal organs after bolus drug
      administration as compared with continuous infusion. Drug effects on plasma
      calcium levels and on urine calcium excretion were similar in both modes of
      alendronate administration. Results of the study indicate that the
      pharmacokinetics (disposition) of alendronate is administration-dependent. The
      total amount found in bone does not directly represent the amount of alendronate
      that is pharmacologically active at the site of action in the bone and that
      affects bone remodeling. The findings suggest that there is no pharmacodynamic
      advantage for continuous infusion of alendronate. It is concluded that the
      preferred mode of administration should be selected according to secondary
      clinical criteria (like incidence of adverse effects and convenience of
      administration).

PMID- 11835210
TI  - Prediction of the aqueous solubility: comparison of the general solubility
      equation and the method using an amended solvation energy relationship.
AB  - An Amended Solvation Energy Relationship (ASER) was recently reported to
      successfully predict the aqueous solubilities of a set of 664 organic compounds.
      The average absolute error and root mean square error are 0.43 and 0.62 log
      units, respectively. When the General Solubility Equation (GSE) is applied to the
      same set of compounds, it gives an average absolute error of 0.45 log units and a
      root mean square error of 0.62 log units. These results are similar to those of
      the ASER method. The advantages and disadvantages of each method are discussed.
      It is shown that when the two methods agree with each other, they also agree with
      the experimentally determined values.

PMID- 11835211
TI  - General solution for diffusion-controlled dissolution of spherical particles. 2.
      Evaluation of experimental data.
AB  - Our general particle dissolution model unified three traditional particle
      dissolution models and predicted that dissolution rates depend on surface
      curvature. Spherical benzocaine particles were prepared with a hot-melt
      dispersion method and physicochemically characterized. Their dissolution behavior
      was studied to evaluate the general dissolution model. A flow-through dissolution
      test system was used which employed an HPLC pump, an HPLC UV detector, a
      cylindrical-shaped dissolution cell, and a data collection system. Single
      benzocaine particle dissolution profiles were determined at ambient temperature
      (22-23 degrees C) in water at a constant flow rate. Dissolution rate normalized
      by surface area was found to be particle radius-dependent and fitted well by the
      general particle dissolution model with a diffusion layer thickness of 110 microm
      and benzocaine diffusion coefficient of 1.4 x 10(-5) cm(2)/s. Analysis of
      literature particle dissolution data also supported this general model. Our
      general model accounts for literature reports of apparent diffusion layer
      thicknesses being smaller for small particles compared with large particles. This
      study supports the applicability of the general particle dissolution model for a
      flow-through dissolution test system.

PMID- 11835212
TI  - A new mechanism for decreasing aggregation of recombinant human interferon-gamma
      by a surfactant: slowed dissolution of lyophilized formulations in a solution
      containing 0.03% polysorbate 20.
AB  - To study the mechanisms by which Tween 20 (polysorbate 20) used in a
      reconstitution solution affects the aggregation of lyophilized recombinant human
      interferon-gamma (rhIFN-gamma), we used four types of buffered formulations
      containing 0.4-5 mg/mL rhIFN-gamma in either 10 mM potassium phosphate or
      phosphate buffered saline: (1) without excipients, (2) with 5% sucrose, (3) with
      0.03% polysorbate 20, or (4) with the combination of 5% sucrose and 0.03%
      polysorbate 20. After lyophilization, infrared spectroscopy was used to analyze
      the secondary structure of the protein in the freeze-dried solid. Each solid
      showed structural perturbation of the protein. Each formulation was reconstituted
      with water or a 0.03% polysorbate 20 solution. Aggregation of rhIFN-gamma after
      reconstitution was measured by optical density at A(350), and recovery of soluble
      protein was determined by high-performance liquid chromatography and ultraviolet
      spectroscopy. After reconstitution with a 0.03% polysorbate 20 solution,
      aggregation levels in all formulations were either reduced or similar to those
      found after reconstitution with water. These results revealed the potential for
      recovery of native protein using the appropriate reconstitution conditions, even
      though the protein is non-native in the lyophilized state. Urea-induced unfolding
      with and without polysorbate 20 as measured by second-derivative ultraviolet
      spectroscopy indicated that a concentration of 0.03% polysorbate 20 lowered the
      free energy of unfolding for rhIFN-gamma (destabilizing). Polysorbate 20 also
      retarded refolding from urea solutions and increased aggregation. At a level of
      0.03%, polysorbate 20 did not protect the protein against surface-induced
      aggregation during agitation. Dissolution times in water versus a 0.03%
      polysorbate 20 solution were measured using a rotating disk electrode for
      lyophilized formulations containing an electrochemically reactive species. The
      presence of 0.03% polysorbate 20 in the reconstitution solution nearly doubled
      the time required for dissolution of the phosphate buffered saline formulation,
      and the sucrose formulations dissolved 33-57% more slowly. Slowing the
      dissolution rates of lyophilized powders allows more time for the protein to
      refold while it decreases the maximum concentration of the protein at the
      dissolution interface, thus reducing the total amount of aggregation.

PMID- 11835213
TI  - The effect of surface charge and partition coefficient on the chemical stability
      of solutes in O/W emulsions.
AB  - Methylparaben (MP) was the model solute used to study the effect of surface
      charge on the rate of degradation in oil-in-water emulsions. The surface charge
      was varied by adding small amounts of phosphatidylglycerol (anionic) or
      stearylamine (cationic) to a standard intravenous lipid emulsion stabilized by
      egg phospholipid. The rates of hydrolysis at pH 8.0 in the water phase, oil
      phase, interface, and aqueous micellar phase were determined by application of a
      four-phase kinetic model. The rate of hydrolysis in the aqueous phase was
      dependent on the zeta potential. This was attributed to the effect of surface
      charge on the pH of the microenvironment of the oil drops through the phenomena
      known as surface acidity. MP in the aqueous phase hydrolyzed at a rate associated
      with the pH of the microenvironment, not the pH of the bulk. The effect of the
      partition coefficient of the solute was studied by substituting ethylparaben
      (EP), propylparaben (PP), and butylparaben (BP) for MP in the emulsions used to
      study the effect of surface charge. The rate of hydrolysis was inversely related
      to the partition coefficient. The effect of surface charge on the rate of
      hydrolysis was evident in the emulsions containing MP and EP. Partitioning had
      the greatest effect on the emulsions containing PP and BP. In general, the effect
      of surface charge predominated when the partition coefficient was small. The
      partition coefficient had a greater effect than surface charge when the partition
      coefficient was large.

PMID- 11835214
TI  - Analysis of the surface energy of pharmaceutical powders by inverse gas
      chromatography.
AB  - The behavior of pharmaceutical solids, during either processing or use, can be
      noticeably affected by the surface energetics of the constituent particles.
      Several techniques exist to measure the surface energy, for example, sessile
      drop, and dynamic contact angle measurements. Inverse gas chromatography (IGC) is
      an alternative technique where the powder surface is characterized by the
      retention behavior of minute quantities of well-characterized vapors that are
      injected into a column containing the material of interest. Recently published
      articles using IGC on pharmaceutical powders have ranged from linking surface
      energetic data with triboelectric charging to studying the effect of surface
      moisture on surface energetics. Molecular modelling has also recently been used
      to explore the links between IGC data and the structural and chemical factors
      that influence surface properties, thereby achieving predictive knowledge
      regarding powder behavior during processing. In this minireview, the reported
      applications of IGC in the analysis of pharmaceutical powders are summarized and
      the major findings highlighted.

PMID- 11835215
TI  - The effect of disorder on the chemical reactivity of an organic solid,
      tetraglycine methyl ester: change of the reaction mechanism.
AB  - Many drugs undergo chemical changes in the solid state, and understanding
      chemical reactivity of organic crystals is a critical factor in the drug
      development process. In this report, the impact of milling on the thermal
      chemical reactivity of an organic solid, tetraglycine methyl ester, was studied
      using DSC, isothermal calorimetry, chemical analysis (HPLC and insoluble residue
      determination), and powder X-ray diffraction. Significant changes in both X-ray
      diffraction patterns and DSC curves were detected after very brief milling (5 s).
      The changes were interpreted as the formation of a disordered phase. The
      disordered phase was tentatively identified as a crystal mesophase that combines
      properties of both crystalline (i.e., long-range order) and amorphous (i.e.,
      glass transition) states. In the disordered material, the reaction mechanism
      changed from the methyl transfer reaction, which was observed in the intact
      crystal, to a polycondensation reaction when the reaction was performed at 165
      degrees C. Such changes in the reaction mechanism occurred in materials milled
      for > 30 s.

PMID- 11835216
TI  - Solute disposition in the rat lung in vivo and in vitro: determining regional
      absorption kinetics in the presence of mucociliary escalator.
AB  - Solute absorption from the airways was compared and modeled in vivo and in vitro
      isolated perfused rat lung (IPRL), and its regional kinetic descriptors in the
      presence of competing mucociliary escalator were estimated. 7.4 kDa fluorophore
      labeled polyhydroxyethylaspartamide (F-PHEA), FITC-labeled dextran 40 (FD-4) and
      sodium fluorescein (F-Na) were used as model solutes. They were reproducibly
      administered into the airways in a range of doses in vivo and in vitro IPRL, and
      their initial deposition and subsequent absorption profiles compared. Each of the
      absorption data was fitted across doses to a kinetic model in which rate
      constants for Michaelis-Menten-type active (V(max,P) and K(m,P)) and/or first
      order passive (k(a,P)) absorption and mucociliary escalator (k(E)) were estimated
      simultaneously. Statistically indistinguishable initial solute distribution was
      ensured in vivo and in vitro. The absorption profiles for F-PHEA were kinetically
      identical in vivo and in vitro, and their modeling analysis revealed the presence
      of competing, solute-independent pulmonary-to-bronchial mucociliary escalator
      with a half-life of 28.9 min. F-PHEA's active absorption was found to be 77 times
      faster than its passive absorption, yet this was present only in the pulmonary
      region. Passive solute absorption was inversely related to solute molecular
      weight [F-PHEA < FD-4 < F-Na]. Bronchial absorption was shown for F-Na in vivo
      and its rate indistinguishable from that from the pulmonary region. Thus, a
      single kinetic model was developed, enabling regional absorption kinetic analysis
      both in vivo and in vitro, in the presence of competing, solute-independent
      mucociliary escalator.

PMID- 11835219
TI  - When ecology and sociology meet: the contributions of Edward A. Ross.
AB  - Edward A. Ross, a key figure in the early history of American sociology,
      developed a conceptualization of natural and social changes of the material
      environment that is virtually forgotten today. In this paper, these topics are
      discussed and located vis-a-vis Ross's intellectual contemporaries and their
      general take on the nature/society relationship. It is argued that ecological and
      sociological ideas in the early twentieth century influenced one another and, in
      the case of Ross, produced a perspective of social change that tried to include
      the dynamics of nature.

PMID- 11835218
TI  - (Physio)logical circuits: the intellectual origins of the McCulloch-Pitts neural
      networks.
AB  - This article examines the intellectual and institutional factors that contributed
      to the collaboration of neuropsychiatrist Warren McCulloch and mathematician
      Walter Pitts on the logic of neural networks, which culminated in their 1943
      publication, "A Logical Calculus of the Ideas Immanent in Nervous Activity."
      Historians and scientists alike often refer to the McCulloch-Pitts paper as a
      landmark event in the history of cybernetics, and fundamental to the development
      of cognitive science and artificial intelligence. This article seeks to bring
      some historical context to the McCulloch-Pitts collaboration itself, namely,
      their intellectual and scientific orientations and backgrounds, the key concepts
      that contributed to their paper, and the institutional context in which their
      collaboration was made. Although they were almost a generation apart and had
      dissimilar scientific backgrounds, McCulloch and Pitts had similar intellectual
      concerns, simultaneously motivated by issues in philosophy, neurology, and
      mathematics. This article demonstrates how these issues converged and found
      resonance in their model of neural networks. By examining the intellectual
      backgrounds of McCulloch and Pitts as individuals, it will be shown that besides
      being an important event in the history of cybernetics proper, the McCulloch
      Pitts collaboration was an important result of early twentieth-century efforts to
      apply mathematics to neurological phenomena.

PMID- 11835220
TI  - The senile mind: psychology and old age in the 1930s and 1940s.
AB  - In the 1930s, some psychologists began to study and discuss the normal and
      pathological mental abilities of old age. This paper explores this research and
      its implications for an emerging definition of old age in the 1930s and 1940s.
      The argument is that these psychologists explained old age in terms of tests they
      had performed on children and young adults. In addition, these professionals
      projected their culturally bound assumptions onto their study of old age. In the
      process, psychologists helped to define old age as a problem that required a
      professional solution.

PMID- 11835221
TI  - The Brown University Psychology Department, spring 1941: an historic photograph.

PMID- 11835225
TI  - Origin and meaning of 'Teratology'.

PMID- 11835224
TI  - A record of fish anomalies from Benghazi area, Libya.

PMID- 11835226
TI  - Pregnancy outcome post renal transplantation.
AB  - BACKGROUND: The success in performing organ transplantations and prevention of
      rejection has resulted not only in a substantial increase in life expectancy, but
      also improvement in the patients' quality of life. Thus, women who underwent
      organ transplantation are now reaching puberty and the age of reproduction. This
      has presented new challenges regarding the teratogenicity and the long-term
      effect of immunosuppressive medications used by these patients. Previous studies
      have shown that pregnancies after renal transplantation are associated with an
      increased risk for both the mother and the fetus. There is, however, very little
      information available on neonatal and long-term pediatric follow-up of babies
      born to mothers who have undergone renal transplantation and have been exposed to
      immunosuppressive medications, compared to controls. We report the experience of
      our center, the largest in Canada, regarding the prenatal and long-term postnatal
      outcome of pregnancies after renal transplantation. METHODS: This is a
      retrospective case series reporting the outcome of 44 consecutive pregnancies
      followed by the Toronto Renal Transplant Program. Follow-up data were gathered on
      the 32 live born children by either a return visit to the clinic or by telephone
      interview. Medical, as well as developmental information, was gathered on all
      children and the study group was compared to controls, matched for maternal age
      (+/-2 years) and smoking status, obtained through the Motherisk Program. RESULTS:
      Of the 44 pregnancies followed by us, there were 32 live-born children delivered
      by 26 mothers and 12 stillborn/abortuses. Twenty-six pregnancies were treated
      with cyclosporine, azathioprine and prednisone, 13 with azathioprine and
      prednisone and five with cyclosporine and prednisone. The mean gestational age at
      delivery in the study group was 36.5 +/- 2.7 weeks compared to 40.2 +/- 1.6 weeks
      in the control group (P < 0.001). The mean birthweight in the study group was
      2.54 +/- 0.67 kg, compared to 3.59 +/- 0.53 kg in the control group (P < 0.0001).
      In the study group there was one child with multiple anomalies and four
      stillbirths compared to zero in the control group. There were also six
      spontaneous abortions and two therapeutic abortions in the study group. On follow
      up (from 3 months to 11 years of age) there was one child with insulin-dependent
      diabetes mellitus, two children with asthma and one child with recurrent otitis
      media. Developmental follow-up revealed one child with moderate to severe
      sensorineural hearing loss, one child with a learning disability and one child
      with pervasive developmental disorder. In none of these cases were there signs of
      perinatal asphyxia. CONCLUSION: There are significantly more stillbirths, preterm
      deliveries and increased incidence of low birth weight in the transplant group.
      Most pregnancies in the study group went well, however, and their offspring had
      normal postnatal growth and development. Further studies with long-term pediatric
      follow-up are needed to delineate their outcome and rule out possible long term
      effects of the immunosuppressive medication on their growth, development,
      reproduction and general health.

PMID- 11835227
TI  - Characterization of the aryl hydrocarbon receptor repressor gene and association
      of its Pro185Ala polymorphism with micropenis.
AB  - BACKGROUND: Genetic background of a fetus contributes to the abnormal development
      after teratogen exposure. In rodents, in utero exposure to dioxins affects male
      external genital development. The effects of dioxins are mediated via the aryl
      hydrocarbon receptor (AHR) and its binding protein, aryl hydrocarbon receptor
      nuclear translocator (ARNT). In mice, aryl hydrocarbon receptor repressor (AHRR),
      which binds to ARNT in competition with AHR, plays a critical negative regulatory
      role in AHR signaling. We attempt to characterize the human AHRR gene and
      investigate the relationship between AHRR polymorphisms and the incidence of
      micropenis, a phenotype of undermasculinization. METHODS: We identified and
      characterized the human homolog of mouse AHRR, taking advantage of the publicly
      available draft version of the human genome sequence. After detecting an AHRR
      protein polymorphism by the direct sequencing of pooled human genomic DNA, we
      evaluated the association between the polymorphism and the presence or absence of
      micropenis (< -2.5 SD) in patients with micropenis and control subjects. RESULTS:
      The deduced sequence for human AHRR (715 residues) and the mouse AHRR protein
      exhibited 81% sequence homology to each other. The Pro185Ala polymorphism was
      identified between the PAS-A region and the highly conserved arginine/cysteine
      rich RCFRCRL/VRC region. Forty-six percent (27/59) of patients with micropenis
      and 27% (22/80) of the controls were homozygous for 185Pro; this difference in
      frequencies was significant (P = 0.03). CONCLUSIONS: Homozygosity for the 185Pro
      allele of AHRR may increase the susceptibility of a fetus to the
      undermasculinizing effects of dioxin exposure in utero, presumably through the
      diminished inhibition of AHR-mediated signaling.

PMID- 11835228
TI  - Tolbutamide alters glucose transport and metabolism in the embryonic mouse heart.
AB  - BACKGROUND: Tolbutamide is a sulfonylurea oral hypoglycemic agent widely used for
      the treatment of non insulin-dependent diabetes mellitus. Tolbutamide produces
      dysmorphogenesis in rodent embryos and becomes concentrated in the embryonic
      heart after maternal oral dosing. Tolbutamide increases glucose metabolism in
      extra-pancreatic adult tissues, but this has not previously been examined in
      embryonic heart. METHODS: CD-1 mouse embryos were exposed on GD 9.5 to
      tolbutamide (0, 100, 250, or 500 microg/ml) for 6, 12, or 24 hr in whole-embryo
      culture. Isolated hearts were evaluated for (3)H-2DG uptake and conversion of
      (14)C-glucose to (14)C-lactate. Glut-1, HKI, and GRP78 protein levels were
      determined by Western analysis, and Glut-1 mRNA was measured by RT-PCR. RESULTS:
      Cardiac (3)H-2DG uptake increased after exposure to 500 microg/ml tolbutamide for
      6 hr, and 100, 250, or 500 microg/ml tolbutamide for 24 hr, compared to controls.
      Glycolysis increased after exposure to 500 microg/ml tolbutamide for 6 or 24 hr
      compared to controls. Glut-1 protein levels increased in hearts exposed to 500
      microg/ml tolbutamide for 12 or 24 hr, and Glut-1 mRNA increased in hearts
      exposed to 500 microg/ml tolbutamide for 24 hr compared to controls. HKI protein
      levels increased in hearts exposed to 500 microg/ml tolbutamide for 6 hr, but not
      12 or 24 hr. There was no effect on GRP78 protein levels in hearts exposed to
      tolbutamide for 6, 12, or 24 hr. CONCLUSIONS: Tolbutamide stimulates glucose
      uptake and metabolism in the embryonic heart, as occurs in adult extra-pancreatic
      tissues. Glut-1 and HKI, but not GRP78, are likely involved in tolbutamide
      induced cardiac dysmorphogenesis.

PMID- 11835229
TI  - Effects of VLA-4 antagonists in rat whole embryo culture.
AB  - BACKGROUND: Pharmacological antagonism of VLA-4 (Very Late Antigen 4,
      alpha(4)beta(1) integrin) has become an attractive target for the treatment of
      predominantly eosinophil mediated disease states such as asthma, allergic
      rhinitis, multiple sclerosis, rheumatoid arthritis, diabetes, and inflammatory
      bowel disease. Gene knockouts of the alpha(4)-integrin subunit of VLA-4 or its
      cell surface ligand, VCAM-1, however, have been shown to result in embryo
      lethality in homozygous null mice due to defects in chorio-allantoic or epi
      myocardial fusion. Although gene knockout phenotypes are not always manifested by
      pharmacological antagonism, those studies suggested that VLA-4 antagonists might
      cause embryo-lethality or drug-induced malformations. METHODS: To test these
      concepts, early neurulating rat embryos were cultured by the methods of New ('78)
      after intra-coelomic microinjection of a VLA-4 blocking antibody or in the
      presence of small molecule VLA-4 antagonists. RESULTS: Defects in chorio
      allantoic fusion were induced after microinjection of VLA4 blocking antibody and
      after continuous exposure to small molecule antagonists. In a minority of
      affected embryos chorio-allantoic fusion was completely blocked whereas the
      majority of affected embryos had only superficial chorio-allantoic fusion and the
      allantois was enlarged and edematous. Although the allantoic mesoderm covered the
      trophoblasts of the chorionic plate and contained blood vessels there was only
      minimal invasion of the trophoblasts by the allantoic mesoderm. The lowest
      observed effect level generally correlated with the IC(approximately 95), as
      determined in 90% plasma. DISCUSSION: Based on these data, VLA-4 antagonism might
      represent a significant risk to the developing embryo/fetus. In vitro exposure,
      however, is "constant" and does not take into account the elimination phase of
      these xenobiotics in vivo. Given the high concentrations required to elicit an
      effect, therapeutic blood levels in vivo may be several fold lower than those
      that affect the conceptus, depending on the tissue penetration of the compound
      and the route of administration. VLA-4 also exists in a range of conformations
      and activation states in vivo and the gene KOs and present studies do not define
      whether these developmental processes are dependent upon a particular activation
      state of VLA-4. Therefore, state-selective antagonists may have an improved
      embryonic safety profile. Additional studies will be required to determine
      potential effects of VLA-4 antagonists on embryo/fetal development in vivo.

PMID- 11835230
TI  - Teratogen update: antithyroid drugs-methimazole, carbimazole, and
      propylthiouracil.

PMID- 11835231
TI  - Cancer in older adolescents and young adults: epidemiology, diagnosis, treatment,
      survival, and importance of clinical trials.
AB  - Cancer in adolescents and young adults has unique features in addition to the
      special medical, physical, psychological, and social needs of patients in this
      age group. The spectrum of malignant diseases is different from that in any other
      period in life, and it is strikingly different from the pattern in older persons.
      More people 15-25 years of age are diagnosed to have cancer than during the first
      15 years of life. During the last 25 years, the incidence of cancer in this age
      range has increased faster while the increase in their cancer survival rates has
      been significantly lower than in younger or older patients, especially in
      comparison to results of the national pediatric cooperative cancer groups. Thus
      the 5-year outcome in 15-19 year olds with leukemias and sarcomas is not only
      worse than in younger patients, but also lower in this population at large than
      in patients of the same age treated at Children's Cancer Group institutions. In
      the United States, only approximately 5% of 15-25 year olds with cancer are
      entered onto clinical trials, in contrast to 60-65% of younger patients. Thus,
      cancer during adolescence and early adult life is an underestimated challenge
      that merits specific resources, solutions, and an international focus.

PMID- 11835232
TI  - Cytogenetic abnormalities and clinical outcome in Wilms tumor: a study by the
      U.K. cancer cytogenetics group and the U.K. Children's Cancer Study Group.
AB  - BACKGROUND: Tumor genetic features reported to correlate with adverse outcome in
      Wilms tumor include karyotype complexity, losses of material from the short arm
      of chromosome 1 and from the long arms of chromosomes 11, 16 and 22 and gain of
      material from the long arm of chromosome 1. This study sought to test these
      associations in a large series of tumors studied by cytogenetic analysis.
      Identification of markers associated with elevated risk of relapse and fatal
      outcome could allow more effective treatment stratification at presentation.
      PROCEDURE: Thirteen member laboratories of the U.K. Cancer Cytogenetics Group
      provided results from a 12-year period. Karyotype abnormalities were correlated
      with clinical data (age, tumor stage, and histology) and outcome data provided by
      the central register of the U.K. Children's Cancer Study Group. RESULTS: Of 127
      abnormal karyotypes, 78 included a reputedly "poor prognosis" feature. Univariate
      survival analysis showed no significant adverse effect for karyotype complexity,
      1p loss or 11q loss. The poor outcome of cases with 16q loss was of borderline
      significance, but this effect was restricted to those tumors with unbalanced
      translocation der(16)t(1q;16q). The association between relapse risk and gain of
      1q material was not significant. Only monosomy 22 was a significant marker of
      poor outcome in univariate analysis (13 cases showing 50% relapse free survival
      at 5 years compared to 79% survival for the remaining 114 cases, P = 0.02). In
      multivariate analysis, significant independent predictors of poor outcome were 1q
      gain (Hazard Ratio 3.4), stage IV disease (HR 5.0), and monosomy 22 (HR 5.9).
      CONCLUSIONS: Loss of chromosome 22 identifies high risk Wilms tumors. The
      prognostic significance of 1q gain, 16q loss and unbalanced translocation
      der(16)t(1q;16q) is unresolved and warrants further investigation.

PMID- 11835233
TI  - Treatment of children and adolescents with localized parameningeal sarcoma:
      experience of the Intergroup Rhabdomyosarcoma Study Group protocols IRS-II
      through -IV, 1978-1997.
AB  - BACKGROUND: We reviewed 611 patients with parameningeal sarcoma entered on
      Intergroup Rhabdomyosarcoma Study Group (IRSG) Protocols-II through IV (1978
      1997), to delineate treatment results and evaluate prognostic factors. PROCEDURE:
      Primary sites were the middle ear/mastoid (N = 138), nasopharynx/nasal cavity (N
      = 235), paranasal sinuses (N = 132), parapharyngeal region (N = 29), and the
      pterygopalatine/infratemporal fossa (N = 77). Treatment was initial biopsy or
      surgery followed by multiagent chemotherapy and radiation therapy (XRT).
      Beginning in 1977, patients with cranial nerve palsy, cranial base bony erosion,
      and/or intracranial extension at diagnosis were considered as having meningeal
      involvement. They received triple intrathecal medications, whole brain XRT, and
      then spinal XRT. These treatments were successively eliminated from 1980 to 1991.
      RESULTS: The 611 patients' overall survival rate at 5 years was 73% (95%
      confidence interval, 70-77%). Favorable prognostic factors were: age 1-9 years at
      diagnosis; primary tumor in the nasopharynx/nasal cavity, middle ear/mastoid, or
      parapharyngeal areas; no meningeal involvement; and non-invasive tumors (T1).
      Thirty-five of 526 patients (6.7%) with information about presence/absence of
      meningeal involvement at diagnosis developed central nervous system (CNS)
      extension at 5-164 weeks (median, 46 weeks) after starting therapy. The estimated
      5-year cumulative incidence rate of CNS extension during the study period was 5
      7% (P = 0.88). CONCLUSIONS: Biopsy, XRT to the target volume, and systemic
      chemotherapy are successful treatments for the large majority of patients with
      localized parameningeal sarcoma. Carefully defining and irradiating the initial
      volume should reduce the risk of CNS failure. Aggressive initial surgical
      management of these patients is unnecessary.

PMID- 11835234
TI  - Fine needle aspiration cytology in the diagnosis and management of children and
      adolescents with Ewing sarcoma and peripheral primitive neuroectodermal tumor.
AB  - PURPOSE: The utility of fine needle aspiration cytology (FNAC) in conjunction
      with immunocytochemistry in the diagnosis of Ewing sarcoma and peripheral
      primitive neuroectodermal tumor, the Ewing family of tumors (EFT), is
      retrospectively described. PATIENTS AND METHODS: During a 10-year period 24
      children and adolescents were diagnosed at Karolinska Hospital to have EFT of
      bone or soft tissue using FNAC. Criteria for diagnosis was based on
      cytomorphology combined with immunocytochemistry. The median age was 14.1 years
      (range 0.7-20.2). FNAC was performed within a median time of 1 day after
      referral. RESULTS: Forty aspiration procedures were performed, 24 at primary work
      up in 23 patients and 16 at suspected relapses in 10 patients. A primary
      cytologic diagnosis of EFT was obtained in 22 of 23 cases. In nine cases with
      primary disease there was no histologic confirmation. Two tumors were on FNAC
      diagnosed as neuroblastoma versus EFT, and EFT, respectively. Histopathology on
      resected tumor tissue from these patients showed EFT and small cell osteosarcoma,
      respectively. Suspected relapse was found to be positive at five and negative at
      11 occasions. Immunocytochemistry was positive for CD45 (LCA) in 0/12, for desmin
      in 2/21, for MIC2 in 15/15, for NB84 in 1/3, for NFP in 7/7, for NSE in 12/18,
      for S-100 in 4/11 and for vimentin in 18/19. CONCLUSIONS: The results show that
      FNAC together with immunocytochemistry is a rapid, physically atraumatic and
      accurate method in diagnosing both primary EFT of bone and soft tissue as well as
      relapses.

PMID- 11835235
TI  - Thyroidal uptake and radiation dose after repetitive I-131-MIBG treatments:
      influence of potassium iodide for thyroid blocking.
AB  - BACKGROUND: In I-131-MIBG therapy, I-131-iodide can be released from the I-131
      MIBG molecule. Hypothyroidism might result from the undesirable irradiation of
      the thyroid gland. To prevent this, stable iodide such as potassium iodide (KI)
      is given to oversaturate the thyroid before I-131-MIBG is administered.
      PROCEDURE: In the present study, the incidence of hypothyroidism (elevated TSH)
      was correlated with the thyroidal uptake of I-131 and dose (MIRD dosimetry) after
      35 individual treatments in ten patients. Iodine-131-MIBG therapy was performed
      using a modified dosage of 1.9-11.1 GBq (50-300 mCi) IV. Premedication with KI
      was done as recommended with a dose of 100 mg KI orally from 2 days before until
      4 weeks after I-131-MIBG. RESULTS: The absorbed thyroidal dose amounted to a very
      variable range of 0.2 (patient # 1) up to 30.0 (patient 3) Gy with 7.1 +/- 7.9 Gy
      per treatment and 24.1+/- 19.2 Gy per patient (mean+/- SD), despite the same and
      compliantly taken KI premedication protocol. Up to now, 4/10 or 40% of patients
      have developed hypothyroidism after a mean follow-up period of 11 months and a
      mean total administered dose of 18.7 GBq (505 mCi). A trend towards higher
      thyroidal doses was seen in the hypothyroid patients. CONCLUSIONS: This study
      observes a general high inter- and intra-individual variability in radio-iodide
      uptake in the thyroid after I-131-MIBG therapy despite KI premedication, as well
      as possible occurrence of hypothyroidism. A dose-response relationship needs
      confirmation on a larger cohort of patients to reach statistical value. An
      alternative thyroid cytoprotection strategy for possible long-term survivors may
      be considered.

PMID- 11835237
TI  - Symposium on new drugs in cancer therapy, November 7-10, 2000.

PMID- 11835236
TI  - Preliminary results of dose intensive pre-irradiation chemotherapy in patients
      older than 10 years of age with high risk medulloblastoma and supratentorial
      primitive neuroectodermal tumors.

PMID- 11835238
TI  - Acute megakaryoblastic leukemia in an infant mimicking polycystic kidney disease.

PMID- 11835239
TI  - Comparison of manual and computer-generated customized blocks for whole brain
      fields used in the treatment of medulloblastoma.
AB  - BACKGROUND: By using CT simulation and three-dimensional planning, we have
      developed a simple but accurate method of producing customized blocks for the
      cranial fields in the treatment of medulloblastoma. We compare here the margins
      and the volume of normal tissues included in the treatment volume with those
      obtained using blocks generated manually. PROCEDURE: Customized blocks for the
      whole brain field are generated using CT planning and autoblock function. The
      clinical target volume (CTV) is defined as the whole cerebrospinal fluid pathway,
      and the whole brain and spinal cord are contoured. A margin of 1.1 cm is
      generated using the autoblock function to account for set-up errors (3-5 mm) and
      penumbra (approximately 7 mm). A separate set of blocks was generated manually
      without the knowledge of the ones generated by the CT-simulator. These 2 sets of
      blocks were compared for a cohort of 7 consecutive patients. RESULTS: Overall,
      the manual blocks and the computer-generated blocks were quite similar. Those
      generated manually had more variations; they were always tighter (median of 6 mm
      tighter; range: 3-7 mm) at the level of the cribriform plate and in 5/7 patients
      were more generous (median of 6 mm more generous, range: 0-6 mm) at the temporal
      lobes. Dosimetric analysis showed that both methods provide adequate coverage of
      the CTV, with 100% of the CTV receiving > 95% of the prescribed dose for both.
      CONCLUSIONS: The customized block method for whole brain fields is simple to use
      and ensures adequate coverage of the target volume.

PMID- 11835240
TI  - Whole body positron emission tomography detected occult infectious foci in a
      child with acute myeloid leukaemia.

PMID- 11835241
TI  - Successful umbilical cord blood transplantation in an infant with ALL failing
      initial autologous peripheral blood stem cell transplantation.

PMID- 11835242
TI  - Clinical and pathologic study of two siblings with osteosarcoma.

PMID- 11835243
TI  - Appendiceal carcinoid tumors in children: does size matter?

PMID- 11835244
TI  - Myeloprotective effect of short term prechemotherapy recombinant granulocyte
      macrophage colony stimulating factor.

PMID- 11835245
TI  - Oxidative stress, p53 expression, and the cytogenetic abnormalities in Langerhans
      cell histiocytosis.

PMID- 11835246
TI  - Congenital acute lymphoblastic leukemia presenting as obstructive jaundice.

PMID- 11835247
TI  - Recurrent mercaptopurine-induced acute pancreatitis: a rare complication of
      chemotherapy for acute lymphoblastic leukemia in children.

PMID- 11835248
TI  - Eosinophilic pneumonia in an infant.

PMID- 11835250
TI  - Use of affinity capillary electrophoresis for characterizing pharmaceutical
      colloidal vehicle systems thermodynamically.
AB  - This review offers a detailed discussion of the interaction between
      pharmaceutical compounds and vehicles using the affinity capillary
      electrophoresis and the microemulsion electrokinetic chromatography. Partition
      coefficients of drugs were calculated between a micelle and an aqueous phases
      from the measurement of the migration time, provided the critical micelle
      concentration and the phase ratio are known. Thermodynamic quantities such as
      enthalpy and entropy changes of micellar solubilization were calculated from the
      temperature dependence of the partition coefficients. Partial specific volumes
      were measured using dynamic light scattering. The logarithm of the partition
      coefficients and the capacity factor in the micellar system were correlated with
      the logarithm of the n-octanol/water partition coefficients.

PMID- 11835251
TI  - Biomedical applications of capillary electrophoresis with laser-induced
      fluorescence detection.
AB  - Capillary electrophoresis (CE) is a high-efficiency analytical technique that has
      had a great impact as a tool in biomedical research, clinical and forensic
      practice in the last ten years. Only in one of the applications, the DNA
      analysis, it has had an explosive exponential growth in the last few years. This
      impact is expressed in an enormous amount of CE articles and many reviews. The CE
      advantages with respect to other analytical techniques: the required very small
      sample volume, rapid analysis, great resolution power and low costs, have made
      this technique ideal for the analysis of a numerous endogenous and exogenous
      substances present in biological fluids. The different modes of CE have been
      coupled to different detection techniques such as UV-absorbance, electrochemical,
      mass spectrometry and laser-induced fluorescence detection (LIFD) to detect
      different nature and molecular size separated analytes. This review focuses
      mostly on the applications of CE-LIFD, to measure drugs and endogenous
      neuroactive substances such as amino acids and monoamines, especially in
      microdialysis samples from experimental animals and humans. CE-LIFD trends are
      discussed: automated faster analysis with capillary array systems, resolution
      power improvement, higher detection sensitivity, and CE systems miniaturization
      for extremely small sample volume, in order to make CE easier and affordable to
      the lab bench or the clinical bed.

PMID- 11835252
TI  - Chiral separation by chromatographic and electromigration techniques. A review.
AB  - This review gives a survey of different chiral separation principles and their
      use in high-performance liquid chromatography (HPLC), gas chromatography (GC),
      supercritical fluid chromatography (SFC), thin-layer chromatography (TLC),
      capillary electrophoresis (CE) and capillary electrochromatography (CEC)
      highlighting new developments and innovative techniques. The mechanisms of the
      different separation principles are briefly discussed and some selected
      applications are shown.

PMID- 11835253
TI  - Capillary electrophoretic analysis of proteins and peptides of biomedical and
      pharmacological interest.
AB  - Capillary electrophoresis (CE) is an automated approach to electrokinetic
      separations that has had a deep impact in all fields of life sciences, including
      biomedical and biotechnological research and clinical and forensic practice. The
      present review highlights aspects of peptides and proteins separations, with
      particular emphasis on macromolecular analytes of biomedical interest. Among the
      various CE techniques available, a novel methodology is here illustrated
      consisting in separations in acidic, isoelectric buffers, which have the
      advantage of protonating the silica wall, thus minimizing interactions of
      proteinaceous material with the siliceous surface, while allowing delivery of
      high voltage gradients, due to their low conductivities. The review ends with
      applications of CE to the analysis of folding/unfolding/refolding/misfolding of
      proteins, a field which has deep implications in the biomedical arena, since it
      is connected to a host of disorders, such as prion protein diseases.

PMID- 11835254
TI  - Analysis and screening of combinatorial libraries using mass spectrometry.
AB  - Mass spectrometry is a highly selective and high throughput analytical technique
      that is ideally suited for the identification and purity determination of large
      numbers of compounds prepared using combinatorial chemistry or for the
      dereplication of natural products. Compounds may be characterized based on
      molecular weight, elemental composition and structural features based on
      fragmentation patterns. When coupled to a separation technique such as high
      performance liquid chromatography (HPLC) or capillary electrophoresis, mass
      spectrometric applications may be expanded to include analysis of complex
      mixtures. However, the slower speed of the separation step reduces the throughput
      of the analysis. This review concerns the application of mass spectrometry to the
      characterization of combinatorial libraries and the screening of library and
      natural product mixtures. Strategies to enhance the throughput of LC-MS are
      discussed including fast HPLC and parallel LC-MS. Also, mass spectrometry-based
      screening methods are described including frontal affinity chromatography-mass
      spectrometry, gel permeation chromatography LC-MS, direct electrospray mass
      spectrometry of receptor-ligand complexes, affinity chromatography-mass
      spectrometry, and pulsed ultrafiltration mass spectrometry.

PMID- 11835255
TI  - Elliptically polarized magnetic fields do not alter immediate early response
      genes expression levels in human glioblastoma cells.
AB  - Expression of immediate early response genes such as c-fos, c-jun, and c-myc in
      response to 1-500 microT resultant (r) 60 Hz elliptically polarized (EP) magnetic
      fields (MFs), typical of environmental MFs polarization under overhead power
      lines, was analyzed in both at transcriptional and translational levels using
      human glioblastoma (T98G) cells. Pseudo synchronized T98G cells at G1 phase were
      exposed to EP-MFs (1, 20, 100, and 500 microTr) for up to 3 h, but produced no
      statistical difference (P>0.05) in the levels of expression ratio at both the
      transcriptional and translational levels at 30 min for c-fos and c-jun and at 180
      min for c-myc after serum stimulation. In addition, exposure of T98G cells to
      linearly (vertical and horizontal) and/or circularly polarized MFs (500 microTr)
      produced no significant change (P>0.05) in the expression ratio at both
      transcriptional and post-transcriptional levels. Thus, there was no evidence that
      linearly or rotating polarized MFs enhanced early response gene expression in
      these studies. These results suggest that environmental MFs at 1-500 microT flux
      density are unlikely to induce carcinogenesis through a mechanism involving
      altered expression of the immediate early response genes.

PMID- 11835256
TI  - Effect of intermittent and continuous exposure to electromagnetic fields on
      cultured hippocampal cells.
AB  - This study was designed to assess the effect of 50 Hz electromagnetic fields
      (EMFs) on hippocampal cell cultures in the presence or absence of either sodium
      nitroprusside (SNP, a NO donor) or Fe2+ induced oxidative stress. One week old
      cultured rat hippocampal cells were exposed to either intermittent EMFs (IEMFs,
      50 Hz, 0-5 mT, 1 min ON/OFF cycles, repeated 10 times every 2 h, 6 times/day
      during 48 h) or continuous EMFs (CEMFs, 50 Hz, 0-5 mT for 48 h). In a second set
      of experiments, the effect on such EMFs applied in combination with oxidative
      stress induced by 0.5 microM Fe2+ or SNP was estimated. At the end of both sets
      of experiments, cell mortality was assessed by lactate dehydrogenase measurements
      (LDH). Neither type of exposure to EMFs was observed to modify the basal rate of
      cell mortality. The exposure to CEMFs in presence of either NO or Fe2+ did not
      induce any significant increase in cell death. However, when cells were exposed
      to EMFs in the presence of NO, we observed a significant increase in cell death
      of 11 and 23% (P<0.001) at 2.5 and 5 mT, respectively. This effect had some
      specificity because IEMFs did not modify the effect of Fe2+ on cell mortality.
      Although the effects of IEMFs reported in this study were only observed at very
      high intensities, our model may prove valuable in trying to identify one cellular
      target of EMFs.

PMID- 11835257
TI  - Decreased DNA repair rates and protection from heat induced apoptosis mediated by
      electromagnetic field exposure.
AB  - In this study, we demonstrate that electromagnetic field (EMF) exposure results
      in protection from heat induced apoptosis in human cancer cell lines in a time
      dependent manner. Apoptosis protection was determined by growing HL-60, HL-60R,
      and Raji cell lines in a 0.15 mT 60 Hz sinusoidal EMF for time periods between 4
      and 24 h. After induction of apoptosis, cells were analyzed by the neutral comet
      assay to determine the percentage of apoptotic cells. To discover the duration of
      this protection, cells were grown in the EMF for 24 h and then removed for 24 to
      48 h before heat shock and neutral comet assays were performed. Our results
      demonstrate that EMF exposure offers significant protection from apoptosis
      (P<.0001 for HL-60 and HL-60R, P<.005 for Raji) after 12 h of exposure and that
      protection can last up to 48 h after removal from the EMF. In this study we
      further demonstrate the effect of the EMF on DNA repair rates. DNA repair data
      were gathered by exposing the same cell lines to the EMF for 24 h before damaging
      the exposed cells and non-exposed cells with H2O2. Cells were allowed to repair
      for time periods between 0 and 15 min before analysis using the alkaline comet
      assay. Results showed that EMF exposure significantly decreased DNA repair rates
      in HL-60 and HL-60R cell lines (P<.001 and P<.01 respectively), but not in the
      Raji cell line. Importantly, our apoptosis results show that a minimal time
      exposure to an EMF is needed before observed effects. This may explain previous
      studies showing no change in apoptosis susceptibility and repair rates when
      treatments and EMF exposure were administered concurrently. More research is
      necessary, however, before data from this in vitro study can be applied to in
      vivo systems.

PMID- 11835259
TI  - Space efficient system for small animal, whole body microwave exposure at 1.6
      GHz.
AB  - A space efficient, whole body microwave exposure system for unrestrained
      laboratory animals utilizing a flared parallel plate waveguide is described. The
      system comprises an Iridium wireless signal source, signal generator, power
      supply and amplifier (400 W), a coax to waveguide transition, an open ended,
      flared parallel plate waveguide, and animal exposure area with a dipole field
      sensing antenna. Across the waveguide aperture the system provides uniform
      exposure (+/-3 dB incident RF power density) for small animals (rats, mice or
      hamsters) in up to 18 standard cages for housing groups of animals. Overall
      system dimensions are 3.6 m (d)x2.4 m (w)x1.6 m (h). Operating at 1.62 GHz, the
      system provided average power density of 3.7 W/m(2) in the cage area, resulting
      in a calculated whole body dose of 0.07 W/kg and a calculated average brain dose
      of 0.19 W/kg.

PMID- 11835258
TI  - Genotoxicity of radiofrequency signals. I. Investigation of DNA damage and
      micronuclei induction in cultured human blood cells.
AB  - As part of a comprehensive investigation of the potential genotoxicity of
      radiofrequency (RF) signals emitted by cellular telephones, in vitro studies
      evaluated the induction of DNA and chromosomal damage in human blood leukocytes
      and lymphocytes, respectively. The signals were voice modulated 837 MHz produced
      by an analog signal generator or by a time division multiple access (TDMA)
      cellular telephone, 837 MHz generated by a code division multiple access (CDMA)
      cellular telephone (not voice modulated), and voice modulated 1909.8 MHz
      generated by a global system of mobile communication (GSM)-type personal
      communication systems (PCS) cellular telephone. DNA damage (strand breaks/alkali
      labile sites) was assessed in leukocytes using the alkaline (pH>13) single cell
      gel electrophoresis (SCG) assay. Chromosomal damage was evaluated in lymphocytes
      mitogenically stimulated to divide postexposure using the cytochalasin B
      binucleate cell micronucleus assay. Cells were exposed at 37+/-1 degrees C, for 3
      or 24 h at average specific absorption rates (SARs) of 1.0-10.0 W/kg. Exposure
      for either 3 or 24 h did not induce a significant increase in DNA damage in
      leukocytes, nor did exposure for 3 h induce a significant increase in
      micronucleated cells among lymphocytes. However, exposure to each of the four RF
      signal technologies for 24 h at an average SAR of 5.0 or 10.0 W/kg resulted in a
      significant and reproducible increase in the frequency of micronucleated
      lymphocytes. The magnitude of the response (approximately four fold) was
      independent of the technology, the presence or absence of voice modulation, and
      the frequency (837 vs. 1909.8 MHz). This research demonstrates that, under
      extended exposure conditions, RF signals at an average SAR of at least 5.0 W/kg
      are capable of inducing chromosomal damage in human lymphocytes.

PMID- 11835260
TI  - Effect of electrical stimulation on musculoskeletal systems; a meta-analysis of
      controlled clinical trials.
AB  - This study was a meta-analysis to examine whether electrical stimulation has
      specific effects in the healing of musculoskeletal repair process and in the
      diminution of symptoms with bone and joint disorders. Using MEDLINE (1966-1999)
      and EMBASE (1985-1999) a search for articles was carried out with four medical
      subject headings. Data were extracted from all the accessed articles and
      additionally collected from appropriate journal lists. A total of 20 randomized
      controlled trials on bones was identified which assessed healing of fractures,
      bone graft, and other conditions; and 29 randomized controlled trials on soft
      tissues and joints were also found, dealing with healing of skin wounds or dermal
      ulcers, soft tissue injury, and other conditions. Using criteria through which
      the quality of studies was assessed, the content of the articles was reorganized
      into a tabular form. The majority of the identified articles reported positive
      findings, but all the trials showed methodological flaws to some extent. Because
      of heterogeneity of the studies and the various outcome measurements, pooling of
      only part of the data was performed. The combined results of 12 trials on bones
      and 16 trials on soft tissues, the cases in which major endpoints were mainly
      union or healing rate, revealed statistically significant effects. The studies in
      this review had some methodological limitations, and the selected pooled trials
      do not constitute acceptable proof that electrical stimulation has specific
      effects on health. However, one cannot ignore the statistically significant
      positive findings reported in the trials, from which extracted data were able to
      be combined.

PMID- 11835261
TI  - Human electrophysiological and cognitive effects of exposure to ELF magnetic and
      ELF modulated RF and microwave fields: a review of recent studies.
AB  - The investigation of weak (<500 microT), extremely low frequency (ELF, 0-300 Hz)
      magnetic field (MF) exposure upon human cognition and electrophysiology has
      yielded incomplete and contradictory evidence that MFs interact with human
      biology. This may be due to the small number of studies undertaken examining ELF
      MF effects upon the human electroencephalogram (EEG), and the associated analysis
      of evoked related potentials (ERPs). Relatively few studies have examined how MF
      exposure may affect cognitive and perceptual processing in human subjects. The
      introduction of this review considers some of the recent studies of ELF MF
      exposure upon the EEG, ERPs and cognitive and perceptual tasks. We also consider
      some of the confounding factors within current human MF studies and suggest some
      new strategies for further experimentation.

PMID- 11835262
TI  - Comparison of dose dependences for bioeffects of continuous-wave and high-peak
      power microwave emissions using gel-suspended cell cultures.
AB  - The study compared bioeffects of continuous wave (CW) microwaves and short,
      extremely high power pulses (EHPP) at the same carrier frequency (9.3 GHz) and
      average power (1.25 W). The peak transmitted power for EHPP was 250 kW (0.5-micro
      s pulse width, 10 p.p.s.), producing the E field of 1.57 MV/m in the waveguide. A
      biological endpoint was the density of yeast cells, achieved after a 6 h growth
      period in a solid nutrient medium (agarose gel) during EHPP or CW exposure. Owing
      to power losses in the medium, the specific absorption rate (SAR) ranged from 3.2
      kW/kg at the exposed surface of the sample to 0.6 mW/kg at 24 mm depth.
      Absorption and penetration of EHPP was identical to CW, producing peak SAR values
      200 000 times higher than the average SAR, as high as 650 MW/kg at the surface.
      CW and EHPP exposures produced highly nonuniform but identical heating patterns
      in exposed samples. Following the exposure, the samples were sliced in a plane
      perpendicular to the wave propagation, in order to separate cell masses exposed
      at different SAR levels. Cell density in the slices was determined by
      nephelometry and compared to unexposed parallel control samples. Cell density was
      strongly affected by irradiation, and the changes correlated well with the local
      temperature rise. However, the data revealed no statistically significant
      difference between CW and EHPP samples across the entire studied range of SAR
      levels (over six orders of magnitude). A trend (P<0.1) for such a difference was
      observed in slices that were exposed at a time average SAR of 100 W/kg and
      higher, which corresponded to peak SAR above 20 MW/kg for the EHPP condition.
      These numbers could be indicative of a threshold for a specific (not merely
      thermal) exposure effect if the trend is confirmed by future studies.

PMID- 11835263
TI  - Long-term exposure of male and female mice to 50 Hz magnetic field: effects on
      fertility.
AB  - The effect of an extremely low frequency (ELF) magnetic field on the fertility of
      adult male and female Swiss mice was investigated. Adult male and female mice
      were exposed to a 50 Hz sinusoidal magnetic field at approximately 25 microT
      (rms) for 90 days before they were mated with unexposed counterparts. There were
      no exposure related effects on the fertility of male or female mice. The number
      of implantation sites, viable fetuses, and the total number of resorptions were
      not significantly affected in females impregnated by males exposed to the 50 Hz
      magnetic field as compared with the control group. The number of implantation
      sites, viable fetuses and the total number of resorptions in exposed females were
      also not statistically different from the control group. There were no
      significant effects on the weights of the testes, seminal vesicles, preputial
      gland or body weights of males exposed to 50 Hz magnetic field. Furthermore, body
      and uterine weights were not affected in females exposed to 50 Hz field; however,
      ovarian weight was significantly increased in females exposed to the same field.
      These results suggest that exposure of male and female mice to low frequency
      magnetic field had no adverse effects on fertility and reproduction in mice.

PMID- 11835264
TI  - Use of spot measurements for assessing residential ELF magnetic field exposure: a
      validity study.
AB  - The purpose of this study was to evaluate residential short term "spot"
      measurements as surrogates for long term personal magnetic field (MF) exposure.
      In an epidemiological study on birth weight and pregnancy delay, MF exposure was
      assessed by taking five spot measurements in each room. For a subsample of 30
      subjects 24 h personal MF measurements were made, and the following exposure
      metrics were calculated: 24 h arithmetic mean, 24 h median, percentage of time
      above 0.15 microT, and percentage of time above 0.29 microT. The 24 h exposure
      metrics were used as gold standards, when evaluating the validity of various
      summary measures calculated from spot measurements for assessing personal
      exposure. Based on Spearman correlation coefficient (r), specificity and
      sensitivity, the average of the spot measurements of a residence resulted in
      least exposure measurement error (misclassification). Also the above bed spot
      value correlated better with the 24 h metrics than any room average. Spot
      measurements performed about equally well in predicting different types of
      exposure metrics.

PMID- 11835265
TI  - The effect of Echis carinatus crude venom and purified protein fractions on
      carbohydrate metabolism in rats.
AB  - Echis carinatus crude venom was fractionated into 11 protein fractions by
      preparative native polyacrylamide gel electrophoresis (PAGE). All fractions
      except fractions 5 and 10 appeared as a single band on analytical native PAGE.
      Purified venom fractions 1, 4, 8, 10 and 11 appeared as single bands on SDS-PAGE
      whereas fractions 2, 3 and 7 contained two bands and fraction 6 contained three
      bands. Fractions 1 and 3 exhibited basic pI (7.3 and 7.6) respectively, while
      fractions 2, 4, 6, 8, 10 and 11 showed an acidic pI. Amino acid analysis also
      showed that crude venom is rich in acidic amino acids. A significant
      hyperglycaemia was produced by i.p. injection of E. carinatus crude venom, after
      15 min of envenomation which persisted even after 24 h. Along with hyperglycaemia
      there was a significant decrease of liver glycogen at 15 min and 1, 12 and 24 h.
      A significant decrease of plasma [pyr + lac] levels was found from 15 min to 24
      h. The liver [pyr + lac] levels increased significantly after 24 h. Skeletal
      muscle [pyr + lac] level was significantly decreased after 24 h of envenomation.
      Fractions 2 and 6 produced the highest increase in plasma glucose after 12 h and
      fraction 7 after 24 h. The plasma insulin level was significantly decreased by
      these three fractions (2, 6 and 7). So it can be hypothesized that the
      hyperglycaemia may result from a direct effect of a venom component on plasma
      insulin. Fractions 7, 8 and 11 caused the highest decrease in plasma [pyr + lac]
      while fractions 1, 2, 3, 4 and 8 produced the most significant decrease in liver
      [pyr + lac]. The most significant increase in lactate dehydrogenase level was
      also produced by fractions 1, 2, 3, 4 and 8.

PMID- 11835266
TI  - Drug metabolic activity of cultured hepatocytes can synchronize with bile acid
      concentration in the medium.
AB  - The regulation of drug metabolic activity of cultured hepatocytes can be applied
      to the evaluation of pharmacokinetics, analysis of drug delivery and the
      bioartificial liver system. It is very difficult to maintain the drug metabolic
      activity mediated by cytochrome P-450 (CYP) 3A. Recently we found that the CYP3A
      aminopyrine N-demethylase (AMND) activity of hepatocytes cultured on collagen
      surface oscillated with culture time. This phenomenon was related to the
      concentration of bile acid in the culture medium. CYP3A, multidrug resistant gene
      2 (MDR2) and heat shock protein 84 (HSP84) mRNA appeared in a manner
      corresponding to this oscillation. When a large quantity of bile acid was taken
      up into hepatocytes from the medium, low AMND activity was observed, and these
      proteins did not appear. When bile acid was secreted and the bile acid
      concentration inside the hepatocytes was low, high AMND activity was obtained,
      and these proteins appeared. In order to clarify the mechanism of oscillation
      between AMND activity and bile acid, 8 microM glycocholic acid was added to the
      culture medium 15 h before the measurement. No oscillation in AMND activity was
      observed in the presence of 8 microM glycocholic acid. Bile acid controls the
      AMND activity in the transcription of hepatocytes.

PMID- 11835267
TI  - Effects of citrinin on iron-redox cycle.
AB  - The ability of the mycotoxin citrinin to act as an inhibitor of iron-induced
      lipoperoxidation of biological membranes prompted us to determine whether it
      could act as an iron chelating agent, interfering with iron redox reactions or
      acting as a free radical scavenger. The addition of Fe3+ to citrinin rapidly
      produced a chromogen, indicating the formation of citrinin-Fe3+ complexes. An EPR
      study confirms that citrinin acts as a ligand of Fe3+, the complexation depending
      on the [Fe3+]:[citrinin] ratios. Effects of citrinin on the iron redox cycle were
      evaluated by oxygen consumption or the o-phenanthroline test. No effect on EDTA
      Fe2+-->EDTA-Fe3+ oxidation was observed in the presence of citrinin, but the
      mycotoxin inhibited, in a dose-dependent manner, the oxidation of Fe2+ to Fe3+ by
      hydrogen peroxide. Reducing agents such as ascorbic acid and DTT reduced the Fe3+
      citrinin complex, but DTT did not cause reduction of Fe3+-EDTA, indicating that
      the redox potentials of Fe3+-citrinin and Fe3+-EDTA are not the same. The Fe2+
      formed from the reduction of Fe3+-citrinin by reducing agents was not rapidly
      reoxidized to Fe3+ by atmospheric oxygen. Citrinin has no radical scavenger
      ability as demonstrated by the absence of DPPH reduction. However, a reaction
      between citrinin and hydrogen peroxide was observed by UV spectrum changes of
      citrinin after incubation with hydrogen peroxide. It was also observed that
      citrinin did not induce direct or reductive mobilization of iron from ferritin.
      These results indicate that the protective effect on iron-induced lipid
      peroxidation by citrinin occurs due to the formation of a redox inactive Fe3+
      citrinin complex, as well as from the reaction of citrinin and hydrogen peroxide.

PMID- 11835268
TI  - Interference of MI-D, a new mesoionic compound, on artificial and native
      membranes.
AB  - MI-D (4-phenyl-5-(4-nitrocinnamoyl)-1,3,4-thiadiazolium-2-phenylamine chloride),
      a new mesoionic compound, decreased the rate of swelling induced by valinomycin
      K+, as well as induced swelling in the presence of nigericin-K+. Shrinkage was
      also affected, suggesting interference with the inner mitochondrial membrane,
      which would affect both fluidity and elasticity. Fluorescence polarization of DPH
      and DPH-PA, probing the core and outer regions respectively, of the DMPC and
      native membranes, indicated that MI-D shifts the midpoint of phase transition to
      higher values and orders of the fluid phase. These alterations in membrane
      fluidity are thus related to MI-D effects on the energy-linked functions of
      mitochondria.

PMID- 11835269
TI  - Autocrine production of basic fibroblast growth factor translated from novel
      synthesized mRNA mediates thrombin-induced mitogenesis in smooth muscle cells.
AB  - Thrombin is known to stimulate smooth muscle cell (SMC) growth in culture but the
      mechanisms underlying growth stimulation remain unclear. Previous works have
      observed a significant increase in platelet-derived growth factor AA and basic
      fibroblast growth factor (bFGF) release by bovine aortic SMC after addition of
      thrombin. The aim of this study was to clarify the link between thrombin, bFGF
      and SMC proliferation by examining the kinetics of autocrine production of bFGF
      by thrombin-stimulated SMC and its contribution to thrombin-induced mitogenesis.
      Experiments were performed to assess the dynamics of thrombin-induced bFGF mRNA
      transcription and to distinguish, following thrombin stimulus, between the
      activation of 'old' bFGF protein and/or bFGF mRNA, or novel mRNA synthesis and
      subsequent translation. Bovine aortic SMCs were stimulated with thrombin in serum
      free culture. bFGF mRNA expression was determined by RT-PCR. Mitogenic activity
      of thrombin was determined by 3H-thymidine uptake. Our results demonstrate that
      the peak of bFGF mRNA expression occurred 24 h after thrombin stimulation.
      Experiments performed with cycloheximide, a translation inhibitor, revealed a
      translation peak later than 24 h after thrombin stimulation. Thrombin-induced
      mitogenic activity in SMCs was partially inhibited by the addition of anti-bFGF
      antibody (p<0.001) and of hirudin (p<0.001). When hirudin was added 24 h after
      stimulation, thrombin-induced mitogenic activity was not inhibited. In
      conclusion, thrombin-induced mitogenesis was partially mediated by the autocrine
      production of bFGF, mainly due to protein synthesis by novel mRNA with a
      transcription peak at 24 h and a later translation peak.

PMID- 11835270
TI  - Differential inhibitory effects of carbon tetrachloride on the hepatic plasma
      membrane, mitochondrial and endoplasmic reticular calcium transport systems:
      implications to hepatotoxicity.
AB  - Mitochondrial, endoplasmic reticular and plasma membrane fractions were isolated
      by a new method from control male Fischer 344 rats and rats given CCl4 by gavage.
      After 1 h of CCl4 treatment, rats were in glucose and pancreatic hormone balance
      but plasma levels of T3 and T4 were decreased 29 and 22%, respectively. After 24
      hours of CCl4 treatment, rats were: hypoglycaemic and insulin and glucagon levels
      were increased 33- and 35-fold, respectively; total T4 levels were decreased 62%;
      while total T3 levels were normalized. In liver fractions from CCl4-treated rats,
      1 h after CCl4 administration: (i) calcium binding was decreased 65% in the
      mitochondrial fraction, 66% in the endoplasmic reticular fraction and 46% in the
      plasma membrane fraction; (ii) calcium uptake was decreased 59% in the
      mitochondrial fraction, 46% in the endoplasmic reticular fraction and 37% in the
      plasma membrane fraction. After 24 h of CCl4 administration: (i) calcium binding
      was decreased 57% in the mitochondrial fraction, 50% in the endoplasmic reticular
      fraction and 71% in the plasma membrane fraction; (ii). calcium uptake was
      decreased 55% in the mitochondrial fraction, 17% in the endoplasmic reticular
      fraction and 53% in the plasma membrane fraction. In vitro studies indicated the
      plasma membrane calcium transport system to be rapidly (within a minute) and
      strongly (>90%) inhibited by CCl4. We conclude that CCl4 produces a differential
      inhibitory effect on the hepatocyte calcium pumps that are implicated with
      hepatocellular damage.

PMID- 11835271
TI  - Age-related changes in the glutathione redox system.
AB  - The effect of aging on the glutathione redox system was evaluated in this study.
      For this purpose, we determined reduced glutathione (GSH) and oxidized
      glutathione (GSSG) in whole blood, glutathione peroxidase (GPx) and glutathione
      reductase (GSSGR) in erythrocytes and selenium (Se) in plasma in 176 healthy
      individuals. We also calculated GSH/GSSG molar ratios. These subjects were
      divided into five groups: group 1 (n=25; 0.2-1 years old); group 2 (n=28; 2-11
      years old); group 3 (n=23; 12-24 years old); group 4 (n=40; 25-40 years old);
      group 5 (n=60; 41-69 years old). GSH levels in groups 1 and 5 were significantly
      lower than the other groups (p<0.001). Conversely, GSSG levels were significantly
      high in these periods (p<0.001). The GSH/GSSG molar ratio was found to be low
      both in the first year of life and in the oldest group (p<0.001, respectively).
      GPx activity in group 5 was increased as compared to the other groups (p<0.001).
      GSSGR activity was significantly lower in the oldest groups than in the other
      groups (p<0.001). Se levels were found to be low in the oldest group (p<0.001).
      Selenium levels of women in group 5 were significantly high as compared to the
      men (p<0.01). We found negative correlations between age and GSH levels (r=0.402;
      p<0.001), selenium levels (r=0.454; p<0.001), GSH/GSSG molar ratio (r=0.557;
      p<0.001) and GSSGR activity (r=0.556; p<0.001). There were positive correlations
      between age and GPx (r=0.538; p<0.001) and GSSG level (r=0.551; p<0.001). In
      conclusion, our findings show that the glutathione redox system is affected by
      age. Oxidative stress increases during the aging process. There is no effect of
      aging on the glutathione redox system according to sex except for the Se level.

PMID- 11835272
TI  - Influence of vitamin E on the levels of fatty acids and MDA in some tissues of
      diabetic rats.
AB  - This study was performed to determine whether vitamin E supplementation in
      streptozotocin-induced diabetic rats treated with insulin could affect the levels
      of fatty acid composition and malondialdehyde (MDA) of brain, liver and muscle
      tissues. Thirty Wistar albino rats were used during the experiments. They were
      randomly divided into three groups, each consisting of six individuals. The first
      group was diabetic, the second was control, and the third was diabetic but fed
      vitamin E. The level of stearic acid in brain tissues decreased (p<0.05) in the
      second and the third groups as compared to the first group. The percentage of
      arachidonic and polyunsaturated fatty acids slightly decreased (p<0.05) in the
      diabetic group in comparison to the second and third groups. The proportion of
      docosahexaenoic acid significantly increased (p<0.01) in the second and third
      groups in contrast to the first group. The level of docosatrienoic was slightly
      higher (p<0.05) in the third group than in other groups. In the liver tissues,
      the proportion of stearic, oleic and total monounsaturated fatty acids was
      slightly higher (p<0.05) in the first group than in the other groups. The level
      of arachidonic, docosahexaenoic, unsaturated and total polyunsaturated fatty acid
      slightly increased (p<0.05) in the second and third groups as compared to the
      first group. The level of myristic and stearic acids in muscle tissue slightly
      increased (p<0.05) in the first group as compared to the second and third groups.
      The proportion of arachidonic, docosahexaenoic and unsaturated fatty acids
      slightly increased (p<0.05) in the second and third groups relative to the first
      group. The amount of MDA was slightly higher in the diabetic group than in the
      other groups in all tissues. The results indicate that vitamin E supplementation,
      in experimental diabetes could play a role in controlling the oxidative status
      and altered fatty acid metabolism in tissues, thereby maintaining favourable
      fatty acid distribution in the tissues affected by diabetic complications.

PMID- 11835273
TI  - Scale-free networks in biology: new insights into the fundamentals of evolution?
AB  - Scale-free network models describe many natural and social phenomena. In
      particular, networks of interacting components of a living cell were shown to
      possess scale-free properties. A recent study((1)) compares the system-level
      properties of metabolic and information networks in 43 archaeal, bacterial and
      eukaryal species and claims that the scale-free organization of these networks is
      more conserved during evolution than their content.

PMID- 11835274
TI  - Branch-specific migration cues in the Drosophila tracheal system.
AB  - The Drosophila tracheal system forms by highly stereotyped migration of the
      tracheal cells, generating an elaborate network of interconnected tubes supplying
      oxygen to all tissues. A major guiding system in the migration process of all
      branches is the dynamic and localized expression of Branchless (Bnl), an FGF-like
      molecule. Bnl triggers the activation of the FGF receptor Breathless (Btl)
      locally in all tracheal cells. Is this the only guiding cue, or do additional
      local signals provide distinct inputs to each branch? Several recent papers
      identify such local signals, relying on contacts with specific cell types and
      with the matrix encountered by the migrating tracheal branches. In particular,
      the paper by Boube et al(1) demonstrates a role for PS integrins in promoting
      migration of a specific tracheal branch.

PMID- 11835275
TI  - Haploid all the way: a new style of asexuality revealed in animals.
AB  - Weeks et al(1) recently reported that they had found a species of mites where the
      parthenogenetic females are haploid. They show that this is caused by
      intracellular bacteria that turn genetic haploid males into haploid females. I
      discuss these findings and attempt to place these observations in evolutionary
      context.

PMID- 11835276
TI  - Control of developmental timing by small temporal RNAs: a paradigm for RNA
      mediated regulation of gene expression.
AB  - Heterochronic genes control the timing of developmental programs. In C. elegans,
      two key genes in the heterochronic pathway, lin-4 and let-7, encode small
      temporally expressed RNAs (stRNAs) that are not translated into protein. These
      stRNAs exert negative post-transcriptional regulation by binding to complementary
      sequences in the 3' untranslated regions of their target genes. stRNAs are
      transcribed as longer precursor RNAs that are processed by the RNase Dicer/DCR-1
      and members of the RDE-1/AGO1 family of proteins, which are better known for
      their roles in RNA interference (RNAi). However, stRNA function appears unrelated
      to RNAi. Both sequence and temporal regulation of let-7 stRNA is conserved in
      other animal species suggesting that this is an evolutionarily ancient gene.
      Indeed, C. elegans, Drosophila and humans encode at least 86 other RNAs with
      similar structural features to lin-4 and let-7. We postulate that other small non
      coding RNAs may function as stRNAs to control temporal identity during
      development in C. elegans and other organisms.

PMID- 11835277
TI  - Enteric glial cells. An upstream target for induction of necrotizing
      enterocolitis and Crohn's disease?
AB  - As a direct consequence of the sophisticated arrangement of its intrinsic
      neurons, the gastrointestinal tract is unique among peripheral organs, in its
      ability to mediate its own reflexes. Neurons of the enteric nervous system are
      intimately associated with enteric glial cells. These supporting cells do not
      resemble Schwann cells, the glial cell found in all other parts of the peripheral
      nervous system, but share many similarities with astrocytes of the central
      nervous system. Ablation of enteric glial cells in adult transgenic mice has
      demonstrated that these cells are essential to maintain the integrity of the
      small intestine. Acute loss of enteric glial cells induces massive pathological
      changes with similarities to necrotizing enterocolitis (NEC) and early Crohn's
      disease. These human conditions share some mechanistic similarities.
      Identification of enteric glial cell dysfunction/loss as sufficient to induce
      necrotic/inflammatory bowel disease may be important to understand the
      pathogenesis of both NEC and Crohn's disease.

PMID- 11835278
TI  - The "tale" of UmuD and its role in SOS mutagenesis.
AB  - Recently, the Escherichia coli umuD and umuC genes have been shown to encode E.
      coli's fifth DNA polymerase, pol V (consisting of a heterotrimer of UmuD'(2)C).
      The main function of pol V appears to be the bypass of DNA lesions that would
      otherwise block replication by pols I-IV. This process is error-prone and leads
      to a striking increase in mutations at sites of DNA damage. While the enzymatic
      properties of pol V are now only beginning to be fully appreciated, a great deal
      is known about how E. coli regulates the intracellular levels of the Umu proteins
      so that the lesion-bypassing activity of pol V is available to help cells survive
      the deleterious consequences of DNA damage, yet keeps any unwarranted activity on
      undamaged templates to a minimum. Our review summarizes the multiple restrictions
      imposed upon pol V, so as to limit its activity in vivo and, in particular,
      highlights the pivotal role that the N-terminal tail of UmuD plays in regulating
      SOS mutagenesis.

PMID- 11835279
TI  - Invasion of mammalian host cells by Plasmodium sporozoites.
AB  - Malaria is transmitted through the bite of an infected mosquito, which introduces
      Plasmodium sporozoites into the mammalian host. Sporozoites rapidly reach the
      liver of the host where they are sequestered, a process probably mediated by
      circumsporozoite (CS) protein. Once in the liver, sporozoites migrate through
      several hepatocytes by breaching their plasma membranes before infecting a final
      hepatocyte with formation of a vacuole around the sporozoite, where development
      occurs into blood stage parasites. We propose that migration through several host
      cells activates sporozoites for ultimate productive invasion. This migration
      triggers sporozoite exocytosis, which is necessary for hepatocyte invasion,
      probably because it provides molecules, such as thrombospondin-related anonymous
      protein (TRAP), likely required for sporozoite invasion with the formation of a
      vacuole. How sporozoites migrate from the skin to the liver and invade
      hepatocytes remains unclear. Understanding this initial stage of malaria is
      crucial for the development of new approaches against the disease.

PMID- 11835281
TI  - Histone ubiquitination: a tagging tail unfolds?
AB  - Despite the fact that histone H2A ubiquitination affects about 10-15% of this
      histone in most eukaryotic cells, histone ubiquitination is among one of the less
      well-characterized post-translational histone modifications. Nevertheless, some
      important observations have been made in recent years. Whilst several enzymes had
      been known to ubiquitinate histones in vitro, recent studies in yeast have led to
      the unequivocal identification of the enzyme responsible for this post
      translational modification in this organism. A strong functional co-relation to
      meiosis and spermiogenesis has also now been well documented, although its
      participation in other functional aspects of chromatin metabolism, such as
      transcription or DNA repair, still remains rather speculative and controversial.
      Because of its nature, histone ubiquitination represents the most bulky
      structural change to histones and as such it would be expected to exert an
      important effect on chromatin structure. Past and recent structural studies,
      however, indicate a surprising lack of effect of (H2A/H2B) ubiquitination on
      nucleosome architecture and of uH2A on chromatin folding. These results suggest
      that this modification may serve as a signal for recognition by functionally
      relevant trans-acting factors and/or operate synergistically in conjunction with
      other post-translational modifications such as for instance acetylation.

PMID- 11835280
TI  - Sonic Hedgehog as a mediator of long-range signaling.
AB  - The ability of Hedgehog (Hh) proteins to exert their biological effects is
      regulated by a series of post-translational processes. These processes include an
      intramolecular cleavage, covalent addition of cholesterol and/or palmitate, and
      conversion into a multimeric freely diffusible form. The processing of Hh
      proteins affects their trafficking, potency, and ability to signal over many cell
      diameters. Accordingly, the loss of gene products required for these processes
      abrogates the Hh proteins' abilities to exert their effects, which can be long
      range, short range, or both. We review here recent evidence demonstrating that Hh
      proteins are directly responsible for their long-range biological effects.
      Additionally, we integrate both genetic and biochemical data to delineate a model
      illustrating how the unusual biochemistry of Hh family members may allow them to
      act as morphogens, signaling over both short and long distances.

PMID- 11835282
TI  - Exploring the etiology of haploinsufficiency.
AB  - The focus of this essay is the phenomenon of haploinsufficiency (HI), a
      manifestation of genetic dominance that arises when only one allele of a normally
      diploid locus is present. Specifically, I examine the nature of HI for
      transcription factor genes. Although the concept of HI applies to many such
      genes, there is a potentially large variety of mechanisms that underlie it. Even
      when the phenomenon is linked in all cases to reduced absolute gene expression
      levels, there are several well-documented cases where the explanation is not
      reduced expression per se but altered stoichiometry. I will discuss the notion of
      haploimbalance in general and evaluate the property of transcriptional synergy
      within the context of HI. This kind of non-linear behaviour can probably explain
      a large proportion of the cases of HI, as well as the variability in most HI
      phenotypes and the fact that several factors in the same pathway may be dosage
      sensitive. For the sake of generality, a theoretical analysis of simple non
      linear HI systems is also attempted. This article is certainly another
      preliminary exploration of the complex matters of HI, which remain an
      intellectual challenge from many points of view.

PMID- 11835283
TI  - The radial-symmetric hydra and the evolution of the bilateral body plan: an old
      body became a young brain.
AB  - The radial symmetric cnidarians are regarded as being close to the common
      metazoan ancestor before bilaterality evolved. It is proposed that a large
      fraction of the body of this gastrula-like organism gave rise to the head of more
      evolved organisms. The trunk was added later in evolution from an unfolding of a
      narrow zone between the tentacles and the blastoporus. This implies that, counter
      intuitively, the foot of the hydra corresponds to the most anterior part
      (forebrain and heart) while the opening of the gastric column gave rise to the
      anus. Two fundamentally different modes of midline formation evolved. In
      vertebrates, the organiser attracts cells from the both sides of the marginal
      zone. These leave the organiser as a unified band. The midline is formed
      sequentially from anterior to posterior. In insects, the midline forms opposite a
      dorsal repelling center, i.e., on the ventral side. This can occur more or less
      simultaneously over the whole anteroposterior extension.

PMID- 11835284
TI  - Paradigm shifts in malaria parasite biochemistry and anti-malarial chemotherapy.
AB  - A fatty acid synthesis (FAS) pathway was recently discovered and established in
      the obligate human parasite Plasmodium falciparum. Its inhibition by triclosan
      (2,4,4'-trichloro-2'-hydroxydiphenyl ether) leads to its classification as a type
      II FAS. Humans, the vertebrate host for the malarial parasite utilize type I FAS,
      which is not inhibited by triclosan. This discovery thus paves the way for novel
      approaches to the treatment of malaria. In direct contrast to the delayed-death
      phenotype associated with poisoning of the apicoplast using certain other drugs,
      the rapid and striking action of triclosan suggests the possibility of developing
      new drug(s) for the treatment of malaria.

PMID- 11835285
TI  - Poly (ADP-ribosylation)--a common control process?

PMID- 11835286
TI  - Effect of disulfiram on the genotoxic potential of acetaldehyde in mouse
      spermatogonial cells.
AB  - The initial purpose of the study was to determine the potential of acetaldehyde
      (Ace) to increase the rate of sister-chromatid exchanges (SCEs) in mouse
      spermatogonia. We tested four doses of Ace (from 0.4 to 400.0 mg/kg), including a
      negative and a positive control group (distilled water and cyclophosphamide,
      respectively). The results showed that all tested doses were SCE inducers. The
      highest tested dose increased the control level more than three times. Also, the
      cumulative frequencies of SCEs per cell were higher in the Ace-treated animals
      than in the control cells. Ace is transformed into acetate through the enzyme
      aldehyde dehydrogenase, a process that may be blocked by disulfiram (Dis)
      generating the accumulation of Ace. The second purpose of the study was to
      determine if the administration of Dis (150 mg/kg) could increase the SCE rate
      produced by non-genotoxic doses of Ace. (0.004 and 0.04 mg/kg). The animals
      treated with the two doses of Ace alone showed no increase in the frequency of
      SCEs; also, Dis by itself was not an SCE inducer. However, the groups of animals
      previously treated with Dis showed an increase of 31 and 60% with respect to the
      values obtained with the two doses of Ace alone. Furthermore, the cumulative
      frequencies of SCEs per cell were higher in the animals administered with both
      compounds together than in those treated with them separately. These results
      suggest the need to extend this type of study to other models.

PMID- 11835287
TI  - Lipid peroxidation, DNA damage, and cellular morphology of R1 Rhabdomyosarcoma
      cell line irradiated in vitro by gamma-rays with different dose rates.
AB  - The study examines the relationship between lipid peroxidation, DNA damage, and
      cell morphology after the exposure of R1 Rhabdomyosarcoma cells to two different
      dose-rates of gamma rays. Exponential cultures of R1 cells were irradiated with
      single dose of 5 Gy at high dose rate (0.833 Gy/min) and low dose rate (0.0707
      Gy/min). The concentration of two aldehydes, malondialdehyde (MDA) and 4
      hydroxynonenal (4-HNE), were determined. DNA damage induction and repair were
      measured by using the alkaline version of the comet assay. Cellular alteration
      was also estimated microscopically as was the frequency of cells with micronuclei
      and proportion of apoptosis and necrosis. These parameters were evaluated
      immediately (time 0) and after different times up to 48 h of incubation in 37
      degrees C, after irradiation. Results indicate that a low dose rate in comparison
      to high dose rate caused a significantly higher increase of aldehydes
      concentration observed at 12 h, followed by obviously higher DNA damage at 48 h
      and altered cellular morphology. The inverse dose-rate effect estimated for the
      gamma rays Co-60 source was found to be related to the measured biochemical and
      morphological parameters.

PMID- 11835288
TI  - Mushroom-derived preparations in the prevention of H2O2-induced oxidative damage
      to cellular DNA.
AB  - Aqueous extracts of the sporophores of eight mushroom species were assessed for
      their ability to prevent H2O2-induced oxidative damage to cellular DNA using the
      single-cell gel electrophoresis ("Comet") assay. The highest genoprotective
      effects were obtained with cold (20 degrees C) and hot (100 degrees C) water
      extracts of Agaricus bisporus and Ganoderma lucidum fruit bodies, respectively.
      No protective effects were observed with Mushroom Derived Preparations (MDPs)
      from Flammulina velutipes, Auricularia auricula, Hypsizygus marmoreus, Lentinula
      edodes, Pleurotus sajor-caju, and Volvariella volvacea. These findings indicate
      that some edible mushrooms represent a valuable source of biologically active
      compounds with potential for protecting cellular DNA from oxidative damage.

PMID- 11835289
TI  - Analysis of the cytotoxicity and mutagenicity of drinking water disinfection by
      products in Salmonella typhimurium.
AB  - We analyzed the cytotoxicity and mutagenicity of the drinking water disinfection
      by-products (DBPs) bromoform (BF), bromoacetic acid (BA), dibromoacetic acid
      (DBA), tribromoacetic acid (TCA), chloroform (CF), chloroacetic acid (CA),
      dichloroacetic acid (DCA), trichloroacetic acid (TCA), 3-chloro-4
      (dichloromethyl)-5-hydroxy-2[5H]-furanone (MX), and potassium bromate (KBrO3) in
      Salmonella typhimurium strains TA98, TA100, and RSJ100 +/- S9. Solvent controls
      of DMSO and ethanol and a positive control of ethylmethanesulfonate (EMS) were
      also analyzed. We developed a rapid microplate-based method to determine the
      cytotoxicity of the DBPs and we determined their mutagenic potencies. The
      distributions of the rank order for the cytotoxicity and mutagenicity of these
      DBPs were compared and the structure-function relationships were identified.
      TA100 -S9 was the most sensitive strain for these DBPs. The rank order of the
      mutagenic potency adjusted with a cytoxicity factor was MX > BA > EMS > DBA > DCA
      > CA with TBA, TCA, BF, and CF not mutagenic. From a structure-function
      perspective, the brominated acetic acids were more cytotoxic and mutagenic than
      their chlorinated analogs. BA was 150x more mutagenic than CA. The mutagenic
      potency of the haloacetic acids was inversely related to the number of halogen
      atoms of the molecule. BA was 36x more mutagenic than DBA. The differential
      cytotoxicity expressed by the DBPs indicated that a cytotoxicity analysis
      enhanced the sensitivity of the mutagenicity data, which resulted in an enhanced
      precision for comparing their relative mutagenic strengths. This information is
      critical when conducting quantitative structure-function analysis of these
      hazardous agents.

PMID- 11835290
TI  - Effects of fasting and intermittent fasting on rat hepatocarcinogenesis induced
      by diethylnitrosamine.
AB  - The influences of fasting on DEN-initiation and of intermittent fasting (IF) on
      the rat liver chemical carcinogenesis process were evaluated in a 52-week long
      assay. Three groups of adult male Wistar rats were used: Groups 1 to 3 were
      treated with a single i.p. injection of 200 mg/kg of diethylnitrosamine (DEN).
      Group 2 was submitted to 48 h fasting prior to DEN treatment. After the 4th week,
      Group 3 was submitted to IF, established as 48 h weekly fasting during 48 weeks,
      while Groups 1 and 2 were fed ad libitum until the 52nd week. All animals were
      submitted to 70% partial hepatectomy and sacrificed at the 3rd and 52nd weeks,
      respectively. Fasting prior to DEN-initiation did not influence the development
      of altered foci of hepatocytes (AFHs) and of hepatic nodules (Group 2 vs. Group
      G1). IF inhibited the development of preneoplastic lesions, since this dietary
      regimen decreased the number and the size of glutathione S-transferase (GST-P)
      positive foci and the number and size of liver nodules (Group G3 vs. Group G1).
      The inhibitory effect of IF was also reflected in the development of clear and
      basophilic cell foci. These results indicate that long-term IF regimen exerts an
      anti-promoting effect on rat hepatocarcinogenesis induced by DEN.

PMID- 11835291
TI  - Alcohol induction of liver nuclear ethanol and N-nitrosodimethylamine metabolism
      to reactive metabolites.
AB  - In previous studies from our laboratory we reported the presence in highly
      purified liver nuclei, free of contamination with other organelles, of an ethanol
      metabolizing system (NEMS) able to lead to acetaldehyde and 1-hydroxyethyl free
      radicals (1HEt). In the present study we tested whether this NEMS is inducible by
      chronic alcohol administration to rats and whether these nuclei also have
      increased ability to bioactivate N-nitrosodimethylamine (NDMA). Sprague Dawley
      male rats (125-150g) were fed with a nutritionally adequate liquid diet
      containing alcohol to provide 36% of total energy (standard Lieber-De Carli rat
      diet), for 28 days. Controls received an isocaloric diet without alcohol. Animals
      were sacrificed, livers were excised and microsomes and purified nuclear
      fractions were prepared. Both microsomes and nuclei from treated animals had
      significantly increased ability compared to controls, to biotransform ethanol to
      acetaldehyde using NADPH as cofactor under an air atmosphere. Both organelles
      also exhibited significantly increased capacity compared to controls, to
      bioactivate NDMA to formaldehyde and to reactive metabolites that bind covalently
      to proteins. Nuclear preparations from control animals were also able to
      metabolize NDMA to formaldehyde and reactive metabolites. Results indicate that
      liver nuclei may have a CYP2E1 able to bioactivate both NDMA and EtOH and that
      these processes are being induced by chronic alcohol drinking. The bioactivation
      of these xenobiotics to reactive metabolites in the neighborhood of nuclear
      proteins and DNA might have significant toxicological implications.

PMID- 11835292
TI  - Susceptibility to DNA damage induced by antibiotics in lymphocytes from
      malnourished children.
AB  - Infectious disease and malnutrition in children are public health problems in
      developing countries. Malnutrition is associated with higher levels of DNA
      damage, and this increased damage could be due to different factors, including
      the possibility that cells from malnourished children could be more susceptible
      to environmental damage. The aim of the present study was to evaluate the
      susceptibility of lymphocytes from malnourished children to DNA damage induced by
      antibiotics by using the comet assay. The same group of malnourished infected
      children were studied before and after a treatment period, and compared to a
      group of well-nourished infected children. Results showed that before and after
      drug treatment, tail length migration was two times greater in malnourished than
      in well-nourished children. The proportion of cells with high damage was also
      increased in malnourished children. Additionally in well-nourished and
      malnourished children, a cell subpopulation (non-damaged cells) more resistant to
      DNA damage induced by antibiotics was observed; this was more prevalent in the
      well-nourished children. Meanwhile, in malnourished children, a cell population
      seems to be more susceptible and reaches higher levels of DNA damage. This might
      help explain the impaired immune response observed in malnourished children. The
      increased DNA migration and the increased proportion of cells with higher levels
      of damage seem to indicate that malnourished children are more susceptible to DNA
      damage induced by drugs.

PMID- 11835293
TI  - The effect of experimental presentation of thin media images on body
      satisfaction: a meta-analytic review.
AB  - OBJECTIVE: The effect of experimental manipulations of the thin beauty ideal, as
      portrayed in the mass media, on female body image was evaluated using meta
      analysis. METHOD: Data from 25 studies (43 effect sizes) were used to examine the
      main effect of mass media images of the slender ideal, as well as the moderating
      effects of pre-existing body image problems, the age of the participants, the
      number of stimulus presentations, and the type of research design. RESULTS: Body
      image was significantly more negative after viewing thin media images than after
      viewing images of either average size models, plus size models, or inanimate
      objects. This effect was stronger for between-subjects designs, participants less
      than 19 years of age, and for participants who are vulnerable to activation of a
      thinness schema. CONCLUSION: Results support the sociocultural perspective that
      mass media promulgate a slender ideal that elicits body dissatisfaction.
      Implications for prevention and research on social comparison processes are
      considered.

PMID- 11835294
TI  - The cognitive-behavioral model of bulimia nervosa: a direct evaluation.
AB  - OBJECTIVE: This study represented the first attempt to directly evaluate Fairburn
      et al's (1986) cognitive-behavioral model of bulimia nervosa--the model on which
      the most widely used treatment for bulimia nervosa is based. METHOD: The major
      predictions of the model were tested using structural equation modeling. Data
      were collected from the responses of 526 subjects to a number of self-report
      measures. RESULTS: The factors of self-esteem, overconcern with weight and shape,
      and dietary restraint accounted for a large proportion of the variance in binge
      eating and purging. The key pathway in the model was the link between overconcern
      with weight and shape and the adoption of purgative behaviors, which then fed
      into a vicious cycle of binge eating and purging. Contrary to Fairburn's
      hypothesis, high levels of dietary restraint did not predict increased binge
      eating. DISCUSSION: The results suggest that the components of Fairburn's model
      may operate to maintain the bulimic cycle in a slightly different way to that
      originally proposed.

PMID- 11835295
TI  - A longitudinal study of the development of dieting among 7-17-year-old Swedish
      girls.
AB  - OBJECTIVE: To examine the extent to which the prevalence of self-reported dieting
      and the wish to be thinner changed in 7-15-year-old girls over a 3-year period,
      and to explore potential differences between cohorts recruited in 1995 and 1999.
      In addition, changes in eating attitudes (Children's Eating Attitudes Test
      [ChEAT]) were compared between 1995 and 1999. METHOD: A three-wave longitudinal
      study including girls (n = 1,076-1,279) in five age groups (7, 9, 11, 13, 15, the
      Main Cohort) and an age-matched cross-sectional sample consisting of 1,759 girls
      (the Societal Cohort). RESULTS: A marked increase of the wish to be thinner was
      evident in the 10-14-year-old age range and significant increases in dieting
      attempts occurred mainly among 9-13-year-old girls. ChEAT scores were
      significantly higher among 11-year-olds in 1999 than in 1995. However, more 7
      year-olds scored above the ChEAT cutoff (</=15) in 1995 compared with 1999.
      DISCUSSION: There was an increasing trend in the wish to be thinner and in
      dieting attempts among 9-14-year-olds. Attitudes and behaviors associated with
      disturbed eating had increased between 1995 and 1999 only among the 11-year-
      olds.

PMID- 11835296
TI  - Rejection of life in anorexic and bulimic patients.
AB  - OBJECTIVES: To investigate eating- disordered (ED) patients' attraction to life
      and death. METHOD: Thirty-two anorexic and 37 bulimic patients were matched by
      age, sex, and socioeconomic status to 37 matched normal controls. Participants
      were administered the Eating Attitudes Test (EAT-26), the Beck Depression
      Inventory (BDI), the Multiattitude Suicidal Tendency Scale (MASS), and the
      Selflessness Scale. RESULTS: ED patients scored significantly higher on the
      Selflessness Scale than normal controls. They are less attracted to and more
      repulsed by life than normal controls. In death variables, attraction to or
      repulsion by, no significant differences were found. These results were not
      influenced by depression. The higher the tendency of ED patients to ignore their
      needs and serve other's needs (high Selflessness scores), the higher their
      tendency to be attracted to death and to be less attracted to life. DISCUSSION:
      ED patients, rather than dwelling on death, reject life. Theoretically, the
      findings support differentiation of death preoccupation to several components.
      Clinically, the findings might direct clinicians to help patients reduce their
      "self-guilt," that is, guilt of promoting their own interests.

PMID- 11835297
TI  - Effect of a very low calorie diet on the diagnostic category of individuals with
      binge eating disorder.
AB  - OBJECTIVE: This study examined the factors associated with the diagnostic outcome
      of obese individuals with and without binge eating disorder (BED) 1 year after
      completing a very low calorie diet (VLCD) program. METHOD: Participants included
      63 individuals with BED, 36 individuals with subthreshold BED, and 29 individuals
      with no binge eating symptoms. Diagnoses before and after VLCD were obtained
      using the Structured Clinical Interview for DSM-IV (SCID) interviews. The
      severity of psychiatric symptoms were assessed using various rating scales.
      RESULTS: Fifty-six percent (n = 36) of the participants who met criteria for BED
      at baseline did not meet diagnostic criteria 1 year later. None of the baseline
      factors were statistically associated with outcome. DISCUSSION: Although the main
      hypothesis was not supported, absence of a BED diagnosis at 12-month follow-up
      after a VLCD diet appears to be associated with less weight gain at 1-year follow
      up regardless of baseline diagnosis.

PMID- 11835298
TI  - Emotional expression and body dissatisfaction.
AB  - OBJECTIVE: The purpose of this study was to examine the relation between
      emotional expression and body dissatisfaction in a sample of young women. METHOD:
      Participants were 141 female undergraduates. They were assessed for emotional
      expression, body dissatisfaction, nonassertiveness, and depressive symptoms. The
      unique relation between emotional expression and body dissatisfaction was
      analyzed using hierarchical multiple regression. RESULTS: Emotional expression
      was related inversely to body dissatisfaction. This association was significant
      after controlling for body mass index, nonassertiveness, and depressive symptoms.
      DISCUSSION: This is the first study to examine the link between emotional
      expression and body dissatisfaction. Findings are discussed in terms of possible
      strategies for modifying shape- and weight-related concerns in women.

PMID- 11835299
TI  - Gender differences in patients with binge eating disorder.
AB  - OBJECTIVE: This study examined gender differences in patients with binge eating
      disorder (BED). METHOD: Participants were 182 adults (35 male, 147 female) who
      were consecutively evaluated for outpatient clinical trials and met criteria for
      BED as outlined in the 4th ed. of the Diagnostic and Statistical Manual of Mental
      Disorders. They were administered a battery of measures to examine developmental,
      eating and weight-related disturbances, and psychological features associated
      with BED. RESULTS: Men and women did not differ significantly on several
      developmental variables (age at first overweight, age at first diet, age at onset
      of regular binge eating, or number of weight cycles). Men had significantly
      higher current body mass index (BMI), highest adult BMI, and were significantly
      more likely to be classified as obese. Men and women did not differ significantly
      on measures of current eating disorder features (binge eating, eating concerns,
      weight or shape concerns) but women reported significantly greater body image
      dissatisfaction and drive for thinness. Men and women did not differ
      significantly on current depression or self-esteem but men reported a greater
      frequency of past drug abuse problems. DISCUSSION: Although men and women who
      present for treatment for BED show many similarities in current eating disorder
      features, we observed a number of gender differences on important developmental
      and physical variables as well as associated psychological features.

PMID- 11835300
TI  - Psychological stress, coping, and symptoms of disordered eating in a community
      sample of young Australian women.
AB  - OBJECTIVE: To investigate the relationships among stress, coping, and symptoms of
      disordered eating in a community sample of young Australian women. METHOD: A
      longitudinal study design was employed. Two mail-out surveys, assessing perceived
      psychological stress, coping strategies, body weight dissatisfaction, dieting,
      and disordered eating behaviors, were completed 6 months apart by 415 young women
      selected from a cohort of the Women's Health Australia Study. RESULTS: Strong
      cross-sectional relationships among the study variables were found. Results of
      longitudinal analyses, however, demonstrated only tenuous relationships among
      stress, coping, and later symptoms of disordered eating. DISCUSSION: These
      results did not support the hypothesis that stress and coping strategies would
      predict disordered eating over time. Some evidence was found for a modest reverse
      relationship between stress and disordered eating. Although contrary to generally
      accepted theoretical models of disordered eating, these findings are consistent
      with those of the few previous longitudinal studies reported. Theoretical
      implications are discussed.

PMID- 11835301
TI  - On the relation of flexible and rigid control of eating to body mass index and
      overeating in patients with binge eating disorder.
AB  - OBJECTIVE: To examine the relationship of flexible and rigid dimensions of
      restrained eating to body mass index (BMI) and overeating in outpatients with
      binge eating disorder (BED). METHOD: Participants were 148 consecutive
      outpatients who met criteria for BED. The Three-Factor Eating Questionnaire
      (TFEQ) was administered to assess Cognitive Restraint, Hunger, and Disinhibition.
      The TFEQ also contains two Cognitive Restraint subscales--Flexible Control and
      Rigid Control. The Eating Disorder Examination-Questionnaire version (EDE-Q) was
      administered to assess frequency of different forms of overeating during the past
      28 days and the attitudinal features of eating disorders. RESULTS: Flexible
      Control and Rigid Control were significantly correlated with each other. They
      were both negatively correlated with BMI, but neither was significantly
      correlated with the frequency of binge eating or other forms of overeating. In
      addition, Flexible Control and Rigid Control predicted almost the same amount of
      variance in BMI. DISCUSSION: BED patients exhibit flexible and rigid control of
      eating that is related to BMI, but not to the frequency of binge eating or other
      forms of overeating. Results of the present study provide preliminary evidence
      that flexible and rigid control of eating may not be a useful distinction in BED
      patients. However, increased restraint, regardless of type, may prove to be of
      benefit with regard to weight control and may not have adverse effects on binge
      eating in obese BED patients.

PMID- 11835302
TI  - Eating attitudes in English secondary school students: influences of ethnicity,
      gender, mood, and social class.
AB  - OBJECTIVE: To examine the effects of ethnicity, gender, socioeconomic position,
      self-esteem, and emotion on eating attitudes in adolescents. METHOD:
      Questionnaire survey of 722 students in two English schools, using Eating
      Attitude Test-26 (EAT), Rosenberg Self-Esteem Scale, and Angold vMood and Feeling
      instruments. RESULTS: EAT scores were significantly higher for Asians and Muslims
      and for mixed-race subjects than for White or African Caribbean subjects (p
      =.003). Adjusted odds ratios for having a very high EAT score (>20) were 2.4 (95%
      confidence interval [CI] 1.0-6.0) in Asians and Muslims and 2.9 (95% CI 1.3-18.6)
      in mixed-race subjects, compared with White subjects. Having only one parent
      employed was also independently associated with a very high EAT score, compared
      with having both parents employed. Similar associations were found for a
      moderately high EAT score (>10) and for a combination of low self-esteem and high
      EAT score. Low self-esteem and depressed mood were independently associated with
      a high EAT score. DISCUSSION: Ethnicity, socioeconomic position, self-esteem, and
      depression, but not gender, were independently associated with eating attitudes.
      Effects of cultural and socioeconomic stresses on eating disorders may be
      mediated through depressed mood and low self-esteem.

PMID- 11835303
TI  - Gastric surgery and restraint from food as triggering factors of eating disorders
      in morbid obesity.
AB  - Obese patients may share some clinical features with anorexia nervosa patients
      because they risk developing an eating disorder when they diet. Methods and
      Results Some common etiological, psychological, and social factors have been
      proposed for both disorders. We present two cases of patients suffering from
      morbid obesity who, after weight loss, presented an intense fear of regaining
      weight and developed anorexic-like symptoms. In the first case, the symptoms
      appeared after gastric reduction surgery. In the second case, a strict diet was
      the triggering factor. DISCUSSION: This paper stresses the need for psychiatric
      evaluation of all patients with morbid obesity who seek treatment in clinical
      settings, in order to identify the factors that may lead to psychiatric
      complications.

PMID- 11835305
TI  - MALDI-TOF mass spectrometry of bacteria.
AB  - The development of MALDI-TOF mass spectrometry methods for the characterization
      of bacteria is reviewed and discussed. The general use of MALDI for the
      characterization of large biomolecules led directly to obvious applications
      involving the analysis of isolated bacterial proteins. More surprising was the
      observation that MALDI-TOF mass spectrometry could be applied directly to crude
      cellular fractions or cellular suspensions and that the resulting data from such
      complex mixtures could provide evidence for chemotaxonomic classification.
      Versatility and the rapidity of analysis led to the rapid development of a number
      of MALDI-TOF methods involving bacteria. Examples of some of the applications
      covered in this review are the analysis of bacterial RNA and DNA, the detection
      of recombinant proteins, the characterization of targeted or unknown proteins,
      bacterial proteomics, the detection of virulence markers, and the very rapid
      characterization of bacteria at the genus, species, and strain level. The
      demonstrated capability of taxonomic classification at the strain level, using
      unprocessed cells, opens the possibility that MALDI-TOF and similar mass
      spectrometry approaches may contribute significantly to fulfilling emerging needs
      for the development of near real-time methods for the characterization of
      bacteria.

PMID- 11835304
TI  - Characterization of intact microorganisms by MALDI mass spectrometry.
AB  - The application of MALDI mass spectrometry to desorb protein biomarkers from
      intact viruses, bacteria, fungus, and spores is the focus of this review.
      Instrumentation, sample collection, sample preparation, and algorithms for data
      analysis are summarized. Optimally these analyses should be carried out in less
      than five minutes. Successful applications are discussed from biotechnology, cell
      biology, and the pharmaceutical industry.

PMID- 11835306
TI  - Computational chemistry: a useful (sometimes mandatory) tool in mass spectrometry
      studies.
AB  - In this review, we present a brief summary of the theoretical methods most
      frequently used in gas-phase ion chemistry. In subsequent sections, the
      performance of these methods is analyzed, paying attention to the reliability of
      geometries, vibrational frequencies, energies, and entropies. The possible
      pathologies of the different methods, in the form of instabilities of the wave
      function or spin contamination problems, are discussed. Several examples are
      presented to illustrate the usefulness of ab initio or density functional theory
      (DFT) methods to predict the existence of elusive molecules and/or to
      characterize non-conventional structures, and to rationalize the charge
      redistributions normally associated with ion-molecule interactions and which
      result in bond-weakening or bond-reinforcement effects. Finally, the role of non
      classical structures in ion-molecule interactions is also illustrated with
      different examples.

PMID- 11835308
TI  - Cytokine signaling in the brain: putting a SOCS in it?
AB  - A new family of cytokine-inducible proteins, termed "suppressors of cytokine
      signaling" (SOCS), was discovered recently; these proteins function as negative
      regulators of signaling pathways involved in the cellular actions of many
      cytokines, growth factors, and hormones. Gene manipulation studies in mice point
      to the central importance of individual SOCS proteins in maintaining homeostasis
      by limiting cellular responses to specific cytokines or growth factors in a
      variety of different physiological systems. Cytokines modulate a wide variety of
      biological responses in the CNS, so members of the SOCS family might play crucial
      roles in regulating intracellular signaling by these effectors in both normal and
      disease states. Although to date studies of the neurobiology of the SOCS family
      have been limited, we know that many SOCS genes are constitutively expressed in
      the developing and adult brain, whereas the expression of others, particularly
      the SOCS1 and SOCS3 genes, can be highly regulated. Furthermore, roles for the
      SOCS are now evident in the modulation of neuroimmunoendocrine functions affected
      by a variety of cytokines, including leptin and members of the growth hormone and
      the interleukin-6/gp130 superfamilies. Overall, these findings point to the SOCS
      as likely crucial negative modulators in the temporal and spatial regulation and
      intensity of cytokine signaling and therefore actions in the CNS.

PMID- 11835309
TI  - Varied actions of proinflammatory cytokines on excitotoxic cell death in the rat
      central nervous system.
AB  - Interleukin (IL)-1beta mediates diverse forms of neurodegeneration and
      exacerbates cell death induced by striatal injection of the excitotoxin alpha
      amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) in the rat brain. The
      objective of this study was to determine whether this effect was specific to IL
      1beta. Injection of IL-1alpha and AMPA in the striatum had effects identical to
      those of IL-1beta, whereas coinjection of IL-6 or tumor necrosis factor (TNF)
      alpha with AMPA failed to induce significant cortical cell death. In contrast to
      IL-1alpha, IL-1beta, and IL-6, TNFalpha significantly reduced (by 38%) the local
      striatal damage. These findings suggest that the effect of IL-1 on AMPA receptor
      mediated cell death in the rat striatum is not mimicked by other proinflammatory
      cytokines. Furthermore, TNFalpha shows neuroprotective effects against acute
      excitotoxic injury.

PMID- 11835311
TI  - Proliferation of Schwann cells and regulation of cyclin D1 expression in an
      animal model of Charcot-Marie-Tooth disease type 1A.
AB  - Overexpression of PMP22 is responsible for the most common form of inherited
      neuropathy, Charcot-Marie-Tooth disease (CMT) type 1A. The PMP22-transgenic rat
      (CMT rat) is an animal model of CMT1A, and its peripheral nerves show the
      characteristic features of ongoing demyelination and remyelination that is also
      seen in CMT1A patients. Since Schwann cell proliferation is a prominent feature
      of peripheral nerves in inherited peripheral neuropathies, we examined
      proliferation and the expression of cyclin D1 in CMT rats. D-type cyclins are
      required for the initial steps in cell division and nuclear import is crucial for
      the function of cyclin D1 in promoting cell proliferation. Like normal
      myelinating Schwann cells in wild-type rats, remyelinating Schwann cells in CMT
      rats show perinuclear cyclin D1 expression. Schwann cells with nuclear cyclin D1
      expression, as well as proliferating Schwann cells, were both associated with
      demyelinated axonal segments. Supernumerary onion bulb Schwann cells, however, do
      not express cyclin D1 and were not proliferating. Thus, cyclin D1 expression and
      its subcellular localization correlate directly with distinct physiological
      states of Schwann cells in this animal model of CMT1A.

PMID- 11835310
TI  - Nerve growth factor-mediated increases in protein methylation occur predominantly
      at type I arginine methylation sites and involve protein arginine
      methyltransferase 1.
AB  - Nerve growth factor (NGF)-specific signal transduction leads to changes in
      protein methylation during neuronal differentiation of PC12 cells (Cimato et al.
      [1997] J. Cell Biol. 138:1089-1103). In the present work, we demonstrate that,
      among NGF-regulated proteins, arginine methylation is more prevalent than
      carboxylmethylation. Type I protein arginine methyltransferase (PRMT) activity
      produces asymmetric dimethylation of the terminal guanidinonitrogen of arginines
      in substrate proteins, particularly glycine and arginine-rich (GAR) segments of
      proteins. Several GAR peptides were used to assay for methyltransferase activity
      and to compete with endogenous cellular proteins for the PRMT activity in PC12
      cell extracts. Peptides derived from fibrillarin and nucleolin, as well as a
      synthetic GAR peptide containing a repetitive GRG motif, are each extremely
      effective at blocking in vitro methylation of the NGF-regulated PC12 cell
      methylated proteins. Myelin basic protein, a substrate for type II PRMT,
      selectively inhibits a 45 kDa protein but is a much less effective inhibitor of
      total methylation at an equimolar concentration. In addition, the fibrillarin-
      and nucleolin-derived peptides were used to detect elevated PRMT activity in
      homogenates of NGF-treated PC12 cells. Finally, immunoprecipitation of PRMT1 from
      PC12 cells provides the first demonstration of an NGF-activated methyltransferase
      and implicates PRMT1 in NGF signal transduction.

PMID- 11835312
TI  - Nitric oxide-induced programmed cell death in human neuroblastoma cells is
      accompanied by the synthesis of Egr-1, a zinc finger transcription factor.
AB  - Nitric oxide (NO) is cytotoxic for human SH-SY5Y neuroblastoma cells. While
      nuclear condensation was visible in cells treated with nitric oxide donors, we
      observed that the plasma membrane remained intact, indicating that NO induced
      apoptotic cell death. We analyzed the NO-induced apoptotic signaling cascade in
      SH-SY5Y cells and observed a striking increase in early growth response (Egr)-1
      promoter activity as a result of NO-induced cell death. Likewise, we detected an
      activation of the transcriptional activation potential of the ternary complex
      factor Elk1, a key transcriptional regulator of serum response element-driven
      gene transcription. Egr-1 is a zinc finger transcription factor that couples
      extracellular signals to long-term responses by altering expression of Egr-1
      target genes. The Egr-1 5'-flanking region contains five serum response elements
      (SRE) that function as genetic elements for stimulus-transcription coupling.
      Moreover, these SREs are binding sites for Elk1, suggesting that NO activated Egr
      1 gene transcription via activation of Elk1. The NO-induced biosynthesis of Egr-1
      was confirmed by Western blot analysis and an NO-dependent increase in the
      transcriptional activation potential of Egr-1 was observed. The fact that NO
      induced neuronal cell death is accompanied by the biosynthesis of Egr-1 suggests
      that Egr-1 may be an integral part of the NO triggered apoptotic signaling
      cascade.

PMID- 11835313
TI  - Suppressive effects of ansamycins on inducible nitric oxide synthase expression
      and the development of experimental autoimmune encephalomyelitis.
AB  - The production of nitric oxide by the inflammatory isoform of nitric oxide
      synthase (NOS2) in brain glial cells is thought to contribute to the causes and
      development of neurological diseases and trauma. We previously demonstrated that
      activation of a heat shock response (HSR) by hyperthermia reduced NOS2 expression
      in vitro, and in vivo attenuated the clinical and histological symptoms of the
      demyelinating disease experimental autoimmune encephalomyelitis (EAE; Heneka et
      al. [2001] J. Neurochem. 77:568-579). Benzoquinoid ansamycins are fungal-derived
      antibiotics with tyrosine kinase inhibitory properties, and which also induce a
      HSR by allowing activation of HS transcription factor HSF1. We now show that two
      members of this class of drugs (geldanamycin and 17-allylamino-17
      demethoxygeldanamycin) also induce a HSR in primary rat astrocytes and rat C6
      glioma cells. Both drugs dose-dependently reduced nitrite accumulation, NOS2
      steady-state mRNA levels, and the cytokine-dependent activation of a rat 2.2-kB
      NOS2 promoter construct stably expressed in C6 cells. These inhibitory effects
      were partially reversed by quercetin, a bioflavonoid which prevents HSF1 binding
      to DNA and thus attenuates the HSR. Ansamycins increased mRNA levels of the
      inhibitory IkappaBalpha protein, suggesting that inhibition of NFkappaB
      activation could contribute to their suppressive effects. Finally, in C57BL/6
      mice actively immunized to develop EAE, a single injection of geldanamycin at 3
      days after immunization reduced disease onset by over 50%. These results indicate
      that ansamycins can exert potent anti-inflammatory effects on brain glial cells
      which may provide therapeutic benefit in neuroinflammatory diseases.

PMID- 11835314
TI  - Contact with astroglial membranes induces axonal and dendritic growth of human
      CNS model neurons and affects the distribution of the growth-associated proteins
      MAP1B and GAP43.
AB  - The development of morphological complexity of CNS neurons is thought to be
      regulated by extracellular factors and cellular contact. To analyze the role of
      contact with astroglia in this process and to determine the intraneuronal
      mechanisms involved, an in vitro system was developed where terminally
      differentiated and polar human CNS model neurons (NT2-N neurons) were cultured on
      a layer of mouse astrocytes or isolated membrane fractions in chemically defined
      medium. Morphometric analysis revealed that physical contact with living
      astrocytes increased the lengths of axonal and dendritic processes and lead to an
      increased number of branch points. Contact with astrocytes also resulted in a
      redistribution of the growth-associated proteins MAP1b and GAP-43 toward the
      growth cones of NT2-N neurons. Astrocyte-contact did not lead to a maturation of
      the neurons as would be detected by an increased expression of tau isoforms
      containing the adult-specific exons 2 and 3. Culture on immobilized membrane
      fractions prepared from astrocytes also increased the morphological complexity of
      the neurons in a qualitatively similar manner. The results indicate that physical
      contact with astrocyte membranes increases the morphological complexity of CNS
      model neurons through a mechanism that involves a redistribution of growth
      associated proteins to neuronal growth cones. NT2-N neurons may provide a useful
      cellular model to analyze cytoskeletal mechanisms during the development of
      terminally differentiated and polar human neurons.

PMID- 11835315
TI  - Development of excitatory synapses in cultured neurons dissociated from the
      cortices of rat embryos and rat pups at birth.
AB  - We studied the development of excitatory synapses in cultured neurons dissociated
      from the cortices of rat embryos at the 18th day of gestation (E18) and rat pups
      at birth (P0). Between 7 and 14 days in vitro (DIV), large increases in the
      amplitudes and frequencies of the spontaneous excitatory postsynaptic currents
      (EPSCs) of both cultured E18 and P0 neurons were observed. The EPSCs of E18
      neurons were mediated primarily by alpha-amino-3-hydroxy-5-methyl-4-iso-xazole
      propionic acid (AMPA) receptors at 7 DIV and by both N-methyl-D-aspartate (NMDA)
      and AMPA receptors at 14 DIV. Consistently, immunostaining indicated significant
      increases in the proportion of the clusters of NR1, an NMDA receptor subunit,
      which were associated with the accumulation of synaptophysin, a presynaptic
      marker, in cultured E18 neurons between 7 and 14 DIV. The proportion of NR1
      clusters residing in synaptic regions and the proportion of synapses that
      colocalized with NR1 clusters in 7-day-old P0 neurons were not different
      statistically from those found in 7-day-old E18 neurons. However, cultured P0
      neurons at 7 DIV displayed clear EPSCs mediated by NMDA receptors. Our results
      suggest that the targeting of NMDA receptors to synaptic regions lag behind the
      synaptic clustering of AMPA receptors during the in vitro development of cultured
      rat E18 cortical neurons. The results further suggest that the cortical neurons
      at P0 differ from those at E19 in certain cellular properties; as a result, the
      currents mediated by the synaptic NMDA receptors in 7-day-old P0 neurons are
      larger than those mediated by the synaptic NMDA receptors in 7-day-old E18
      neurons.

PMID- 11835316
TI  - Inhibition by R(+) or S(-) pramipexole of caspase activation and cell death
      induced by methylpyridinium ion or beta amyloid peptide in SH-SY5Y neuroblastoma.
AB  - Cell models of neurodegenerative diseases (NDD) can involve expression of mutant
      nuclear genes associated with Mendelian forms of the diseases or effects of
      toxins believed to replicate essential disease features. Death produced by
      exposing neural cells to methylpyridinium ion (MPP(+)) or neurotoxic beta amyloid
      (BA) peptides is frequently used to study features of the sporadic, most
      prevalent forms of Parkinson's disease (PD) and Alzheimer's disease (AD),
      respectively. We examined in replicating SH-SY5Y human neuroblastoma cells the
      release of cytochrome C into cytoplasm, activation of caspases 9 and 3, and loss
      of calcein retention as markers of the "mitochondrial" pathway of cell death.
      Exposure to 5 mM MPP(+), which induces apoptotic cell death within 18-24 hr,
      released cytochrome C within 4 hr, activated caspases 9 and 3, and reduced
      calcein accumulation. BA 25-35 peptide produced more rapid and greater elevations
      of caspase 3 activity; no effects were observed with the nontoxic BA 35-25
      reverse sequence. The dependence on mitochondrial transition pore (MTP) activity
      of MPP(+)-induced caspase activations was demonstrated by preincubation with
      bongkreckic acid, which blocked elevations of caspases 9 and 3. Stereoisomers of
      pramipexole (PPX), a free radical scavenger and inhibitor of MTP opening,
      inhibited caspase activation (MPP(+) and BA) and restored calcein accumulation
      (MPP(+)). Our results demonstrate that MPP(+) and BA can induce cell death
      through MTP-dependent activation of caspase cascades. PPX stereoisomers interfere
      with activation of these cell death pathways and may be useful clinically as
      neuroprotectants in PD and AD and related diseases.

PMID- 11835317
TI  - Overexpression of S100beta in transgenic mice does not protect from serotonergic
      denervation induced by 5,7-dihydroxytryptamine.
AB  - Transgenic mice overexpressing S100beta were used to examine whether the chronic
      elevation of this protein alters the response to selective partial serotonergic
      lesions produced by bilateral intracerebroventricular injections of 5,7
      dihydroxytryptamine (5,7-DHT). Basal levels of S100beta mRNA examined by in situ
      hybridization were two- to threefold higher throughout the brain in transgenic
      than in control mice, whereas 5-HT levels in forebrain were similar in both.
      After the 5,7-DHT-induced lesions, no differences were found in the S100beta mRNA
      levels in either normal or transgenic mice. At 5 and 60 days after the lesion,
      forebrain 5-HT levels were reduced by 56% and 35%, respectively, in control mice
      and by 51% and 35%, respectively, in the transgenic mice. Analysis of the 5-HT
      immunostaining showed a marked decrease of the immunoreactivity in various brain
      regions, which was comparable at the two intervals postlesion. One exception was
      the medial hypothalamus, where an almost complete disappearance of 5-HT
      immunoreactivity was observed in the medial region at 5 days after lesion,
      followed by a marked reinnervation 60 days later. These hypothalamic changes were
      seen in both controls and S100beta-overexpressing transgenic mice. Quantitative
      analysis of the density of 5-HT transporter sites using [(3)H]citalopram binding,
      a marker of serotonergic terminals, showed a marked decrease in different brain
      regions at both 5 and 60 days after 5,7-DHT injections. No difference in basal
      and postlesion levels of [(3)H]citalopram binding was seen between transgenic and
      control mice. In conclusion, this study demonstrates that constitutive
      overexpression of S100beta in transgenic mice does not modify serotonin levels
      during development, nor does it protect the serotonergic neurons from selective
      neurotoxicity or modify the serotonergic sprouting induced by partial lesion.

PMID- 11835318
TI  - Alpha1-antichymotrypsin/Alzheimer's peptide Abeta(1-42) complex perturbs lipid
      metabolism and activates transcription factors PPARgamma and NFkappaB in human
      neuroblastoma (Kelly) cells.
AB  - Amyloid-beta peptide (Abeta) and the serpin proteinase inhibitor alpha1
      antichymotrypsin (ACT) are components of the amyloid plaques associated with
      Alzheimer's disease (AD). Abeta exists in soluble monomeric and oligomeric forms
      and in an insoluble polymerised fibrillar form, but it is not clear which of
      these plays the most important role in the etiology of AD. In vitro, Abeta(1-42)
      interacts with ACT, and as a result of this, ACT loses its proteinase inhibitor
      activity and polymerisation of Abeta(1-42) is promoted. Here we provide evidence
      that new molecular forms resulting from incubation of ACT with Abeta(1-42) have
      multiple cellular level effects on neuronal cells. The mixture of soluble Abeta
      and an ACT/Abeta complex formed by 2 hr incubation at a 10:1 molar ratio of
      Abeta:ACT strongly induce cellular proliferation and expression of transcription
      factors peroxisome proliferator-activated receptor-gamma (PPARgamma) and
      NFkappaB, and also increase uptake and depress degradation of native and oxidised
      low-density lipoprotein (LDL) by cells. Similar but less pronounced effects are
      seen when cells are exposed to the Abeta peptide alone preincubated for 2 hr.
      Abeta(1-42) and to a lesser extent ACT/Abeta(1-42) complex mixture prepared by 2
      hr incubation both inhibit association of native LDL with cells. Neither ACT
      alone nor the Abeta(1-42) and ACT/Abeta(1-42) forms prepared by 24-hr incubation
      show any significant effects in these assays. We propose that specific molecular
      forms of Abeta(1-42) and ACT/Abeta(1-42) complex mixture, both dependent on the
      abundances of Abeta(1-42) and ACT/Abeta(1-42) in vivo and on their time of
      exposure to each other, have cellular effects which are important for the
      initiation and progression of the pathologies associated with AD.

PMID- 11835319
TI  - Potentiation of nuclear activator protein-1 DNA binding following brief exposure
      to N-methyl-D-aspartate in immature cultured rat hippocampal neurons.
AB  - Similar potentiation was seen with the nuclear transcription factor activator
      protein-1 (AP1) binding in rat hippocampal neurons cultured for 3 and 9 DIV, when
      determined immediately after exposure to 500 microM N-methyl-D-aspartate (NMDA)
      for 60-120 min. Growth-associated protein-43 was markedly expressed in
      hippocampal neurons cultured for 3-5 DIV, with a decline up to 9 DIV. In immature
      neurons cultured for 3 DIV, NMDA was effective in significantly potentiating AP1
      binding even in the presence of Mg(2+) with less potency than in the absence of
      Mg(2+) when determined immediately after sustained exposure for 120 min. When
      determined 120 min after brief exposure for 5 min, by contrast, NMDA
      significantly potentiated AP1 binding at a range of 100-500 microM only in the
      absence of Mg(2+) in immature neurons cultured for 3 DIV. At least 60 min was
      required for significant potentiation of AP1 binding as an interval between brief
      exposure and subsequent cell harvest. Dizocilpine abolished the potentiation
      determined 120 min after brief exposure to 500 microM NMDA, and both dantrolene
      and nifedipine were similarly effective in significantly preventing the
      potentiation at 10-50 microM. These results suggest that NMDA may potentiate AP1
      binding following a sustained increase in intracellular free Ca(2+)
      concentrations through influxes across NMDA-operated and L-type voltage-sensitive
      Ca(2+) channels, in addition to release from intracellular Ca(2+) stores, in
      immature cultured rat hippocampal neurons.

PMID- 11835320
TI  - Plasma melatonin, pinealocyte morphology, and surface receptors/antigen
      expression on macrophages/microglia in the pineal gland following a high-altitude
      exposure.
AB  - The present study examined the effects of high-altitude exposure on the pineal
      gland, the main source of production of melatonin. It was surmised that hypoxia
      experienced at high altitude, caused by decreased oxygen tension in the ambient
      air, might lead to some structural alterations in the pineal gland and, hence,
      affect its melatonin production. Adult Wistar rats were exposed to an altitude of
      8,000 m for 2 hr in an altitude chamber and then sacrificed at various time
      intervals after the exposure. Normal rats kept at ground level were used as
      controls. Blood samples were collected at various time intervals for measurement
      of plasma melatonin level, and the pineal glands from both groups were processed
      for electron microscopy and immunohistochemistry. The plasma melatonin level
      showed a steady increase following altitude exposure peaking at 7 days and
      returned to control levels thereafter. Between 1 and 4 days after altitude
      exposure, the mitochondrial number and lipid droplets in the pinealocytes
      appeared to be reduced compared with those in control rats. At 7 days, however,
      the mitochondrial numbers and lipid droplets were noticeably increased. At the
      same time interval, the expression of complement type 3 receptors and major
      histocompatibility class II antigens as detected with the antibodies OX-42 and OX
      6, respectively, in macrophages/microglia was up-regulated compared with that in
      the control rats and those killed at earlier times. This was attributed to the
      increased serum melatonin after the altitude exposure. By 14 and 21 days, the
      ultrastructure of pinealocytes and immunoreactivity of macrophages/microglia were
      comparable with those in the control rats. We conclude from this study that an
      altitude exposure in rats leads to an increase in melatonin production, which
      returned to control levels with passage of time.

PMID- 11835321
TI  - Differential effects of glucocorticoids and gonadal steroids on glutathione
      levels in neuronal and glial cell systems.
AB  - The aim of the present study was to investigate the short- and long-term effects
      of glucocorticoids [corticosterone (CORT), dexamethasone (DEX), 6
      methylprednisolone (6-MP)] and gonadal steroids [17beta-estradiol (E(2)),
      progesterone (PROG), testosterone (TEST)] on the levels of the antioxidant
      glutathione (GSH) in different cell systems of the CNS (neuronal hippocampal HT22
      cells, primary hippocampal and neocortical brain cells, and C(6) glioma cells).
      In HT22 cells, steroids exerted mainly long-term effects. Significant increases
      of GSH levels were detectable after a 24 hr treatment with 10(-7) M of DEX (122%
      +/- 5%), 6-MP (208% +/- 32%), E(2) (134% +/- 10%), and TEST (155% +/- 17%). A
      significant decrease occurred after incubation with PROG for 24 hr (79% +/- 9%).
      In primary hippocampal cultures, a 24 hr treatment with DEX (140% +/- 8%), E(2)
      (123% +/- 6%), and PROG (118% +/- 5%) led to significant increases of the GSH
      levels, whereas, in neocortical primary cultures, only an incubation with E(2)
      increased GSH (149% +/- 8%). In C(6) cells, hormone treatment led to both
      significant short-term (1 hr: CORT 114% +/- 5%, DEX 90% +/- 3%, E(2) 88% +/- 3%;
      3 hr: DEX 115% +/- 5%, E(2) 122% +/- 6%, TEST 78% +/- 4%) and significant long
      term (24 hr: CORT 74% +/- 4%, 6-MP 84% +/- 5%, E(2) 115% +/- 6%, PROG 91% +/- 4%,
      TEST 116% +/- 5%) effects. In summary, we were able to demonstrate differential
      effects of steroids on GSH levels in different cellular CNS models, showing an
      important influence of steroids and especially E(2) on antioxidative cellular
      functions in neuronal and glial cells.

PMID- 11835322
TI  - Detection of prolactin receptor mRNA in the corpus striatum and substantia nigra
      of the rat.
AB  - The observation of prolactin modulation of the nigrostriatal dopaminergic system
      suggests the expression of prolactin receptor in the corpus striatum or
      substantia nigra. The present study investigated expression of prolactin receptor
      mRNA in tissues microdissected from the corpus striatum and substantia nigra of
      the rat. By using reverse transcription PCR combined with Southern hybridization,
      the long form of prolactin receptor mRNA was detected in the substantia nigra,
      caudate putamen, globus pallidus, and ventral pallidum in ovariectomized rats,
      whereas the short form was not detectable in any of these areas. Estrogen had no
      effect on expression of the long-form mRNA in the substantia nigra and corpus
      striatum. By using the RNase protection assay, the expression of both short and
      long forms of prolactin receptor mRNA was observed in the corpus striatum in
      ovariectomized rats. Again, levels of expression were not significantly altered
      by estrogen treatment. Both forms of prolactin receptor mRNA were clearly
      expressed in the choroid plexus and were up-regulated by estrogen treatment. The
      expression of both forms of prolactin receptor mRNA in nigrostriatal areas may
      help to support the hypothesis that prolactin has direct actions on these brain
      regions.

PMID- 11835323
TI  - Serum transferrin receptor in the evaluation of the iron status in elderly
      hospitalized patients with anemia.
AB  - The aim of the present study is to evaluate in an elderly hospitalized population
      the diagnostic value of the serum transferrin receptor (sTfR) in distinguishing
      IDA (iron deficiency anemia) from ACD (anemia of chronic disease) as compared to
      conventional laboratory tests of iron metabolism, especially serum ferritin. In a
      prospective study, 34 patients with IDA and 38 patients with ACD (a chronic
      disorder in 23 and an acute infection in 15) were evaluated using iron status
      tests including serum transferrin receptor assay. The iron stores were assessed
      by bone marrow examination. sTfR levels were elevated (>28.1 nmol/L) in 68% of
      the IDA patients but also in 43% of the patients with ACD-chronic inflammation
      and 33% with ACD-acute infection. Serum ferritin was the best test to
      differentiate IDA from ACD patients. We conclude that serum ferritin is a more
      sensitive and specific parameter than the sTfR assay to predict the bone marrow
      iron status in an elderly anemic population.

PMID- 11835324
TI  - Kinetics of hemopoietic recovery after peripheral blood stem cell
      transplantation: impact of stem cell purification and G-CSF.
AB  - We investigated the role of stem cell purification and G-CSF (early vs. delayed
      vs. no G-CSF) administration on hemopoietic recovery and supportive care
      requirements after stem cell transplantation. Thirty-two patients submitted to
      autologous CD34(+) peripheral blood stem cell transplantation (PBSCT) were
      studied, and data were compared to patients undergoing unfractionated peripheral
      blood stem cell transplantation (uPBSCT) matched for age, disease, and
      conditioning regimen. Except for PMN, hemopoietic recovery was significantly
      slower and supportive care requirements were significantly higher after CD34(+)
      PBSCT. Median time to PMN >0.5 x 10(9)/l was 13 days (range 9-27) and 13 d (range
      9-23); reticulocytes (Ret) >1% was 14.5 d (range 12-34) and 12 d (range 10-27);
      high-fluorescence reticulocytes (HFR) >5% was 12 d (range 9-26) and 9 d (range 7
      11); platelets >50 x 10(9)/l and >100 x 10(9)/l was 20 d (range 10-240), 12 d
      (range 9-60) and 33 d (range 15-720), 15 d (range 11-210). When the analysis was
      performed on subgroups of patients (early/delayed/no G-CSF), early G-CSF
      significantly promoted PMN recovery (>0.5 x 10(9)/l and >1.0 x 10(9)/l) compared
      to no G-CSF, without affecting RBCs or platelet recovery. Delayed G-CSF did not
      improve PMN recovery compared to patients not receiving G-CSF, did not result in
      a significant reduction of drug requirements, and had a negative impact on
      erythroid and platelet recovery. In conclusion, these preliminary data suggest
      that G-CSF is useful if given early after CD34(+) PBSCT. CD34(+) PBSCT may
      overall require a significant increase of resource utilization that should be
      outweighed by proven clinical benefit.

PMID- 11835325
TI  - Supplemental peripheral blood stem cells to decrease marrow rejection in adult
      patients with severe aplastic anemia.
AB  - Twenty-two multi-transfused patients with a long duration of severe aplastic
      anemia (SAA) received a transplant from an HLA-matched donor after
      cyclophosphamide (CY) plus antithymocyte globulin plus procarbazine using CD34(+)
      enriched blood stem cells + fresh marrow. Peripheral blood stem cells (PBSC) were
      collected on days 5 and 6 of G-CSF (10 microg/kg/day), and T cells were depleted
      using an immunoadsorption column (n = 15) or magnetic cell sorting (n = 7).
      Marrow harvesting was performed 48 hr after the last leukapheresis. Two patients
      (9.1%) that developed graft failure had a successful engraftment again using
      unpurged PBSC. Median time to neutrophils > or = 0.5 x 10(9)/l and platelets > or
      = 20 x 10(9)/l without platelet transfusions were 12 days and 17 days,
      respectively. Acute graft-versus-host disease (GVHD) grade II occurred in four of
      22 patients. No patient developed grade III or IV acute GVHD. Four of the
      evaluable 21 patients had chronic GVHD. One patient developed extensive disease.
      Three patients (13.6%) died from CY-induced heart failure, extensive-type chronic
      GVHD, and sepsis of unknown cause. The Kaplan-Meier estimate of survival was
      83.9% (95% CI, 70.1-95.2%) with a median follow-up duration of 33.5 (6-44)
      months. CD34(+)-enriched PBSC in combination with unmanipulated marrow seem to
      play a role in overcoming the sensitization to histocompatibility antigens
      without an apparent increase in GVHD. The stem cell component therapy may be
      feasible for the high-risk SAA adult patients.

PMID- 11835326
TI  - Temporal sequence of splenic dysfunction in sickle cell disease.
AB  - Sickle cell patients develop splenic dysfunction early in the course of their
      disease as shown by failure to visualize the organ on technetium-99m colloid
      scintigraphy. However, preliminary studies from our center have shown that, when
      the spleen is not demonstrable on colloid uptake, it may be visualized on
      technetium-99m heat-denatured RBC scintigraphy. With time, however, the spleen
      can no longer be visualized with both tests in many patients. We have studied 46
      patients aged 2 to 16 years, which included 36 SS, 7 Sbeta(0) thal, and 3 SD.
      Eighteen (39.1%) had normal splenic colloid uptake (Group 1), 15 (32.6%) had
      partial uptake (Group 2), and 13 (28.3%) had absent uptake (Group 3). When the
      patients in Group 1 were compared to those in the two other groups, there was no
      significant difference in the mean age and Hb F values. However, the mean Hb of
      10.2 g/dl in Group 1 was significantly higher than the value of 9.0 g/dl in the
      other two groups. In addition, 60% of the SS patients with normal uptake and 40%
      of those with partial or absent uptake had co-existing alpha-thal trait; the
      difference in this proportion is significant (chi(2) = 85, P < 0.0001). Heat
      denatured RBC scintigraphy was carried out on five patients in Group 2, and the
      spleen was visible in all, while of 12 children in Group 3, the spleen was
      visible only in 4 patients. This study demonstrates that the phagocytic function
      of the spleen, which is tested by colloid uptake, is the first to be lost while
      the filtration function, tested by denatured RBC uptake, persists for much
      longer. This finding may have significant implications for the clinical
      symptomatology and therapeutic strategies of sickle cell disease.

PMID- 11835327
TI  - CD56 expression in myeloperoxidase-negative FAB M5 acute myeloid leukemia.
AB  - CD56 is a natural killer (NK) cell marker that has been identified in
      approximately 15-20% of acute myeloid leukemia (AML) cases, where it has been
      associated with monocytic morphology and chromosomal abnormalities such as
      trisomy 8, t(8;21), t(15;17), and 11q23 rearrangements. The clinical
      presentation, chromosomal abnormalities as detected by fluorescent in-situ
      hybridization (FISH), and clinical outcomes of 7 patients with AML are presented.
      These cases were characterized by French-American-British (FAB) M5 morphology,
      myeloperoxidase (MPO) negativity, and co-expression of myelomonocytic and NK cell
      associated antigens (CD11c(+), CD13(+), CD15(+), CD33(+), HLA-DR(+), and
      CD56(+)). All patients presented lymph node, hepatic, or splenic involvement at
      diagnosis. Despite the homogeneous morphologic and immunophenotypic
      characteristics the outcomes varied considerably. Two patients died during
      induction therapy, but the other five patients attained complete remission (CR).
      Of these five patients, 4 have received a bone marrow transplantation (autologous
      or allogeneic) and 3 of them are in CR (median follow-up: 45 months). The three
      patients with 11q23 rearrangements had a poor outcome and died of their disease
      within 1 year of diagnosis. Further studies with a larger group of patients would
      help establish the actual prognostic value of these morphologic, immunophenotypic
      and cytogenetic features.

PMID- 11835328
TI  - Importance of RDW value in differential diagnosis of hypochrome anemias.
AB  - Red cell distribution width (RDW) was studied in adults carrying delta-beta
      thalassemia traits (deltabeta-TT) who were 20-40 years of age (n = 29), beta
      thalassemia traits (beta-TT) with an age range of 18-60 years (n = 49), iron
      deficiency anemia (IDA) in individuals aged 1-18 years (n = 27), and in controls
      with an age range of 20-40 years (n = 20). Although red blood cell count, MCV,
      and MCH values showed no statistically significant differences between deltabeta
      TT and beta-TT, the mean RDW value was significantly higher in deltabeta-TT
      (20.14 +/- 1.21) compared to beta-TT (14.88 +/- 1.77) (P < 0.001). No difference
      was observed between the means of RDW in deltabeta-TT and IDA (18.00 +/- 1.94) (P
      > 0.05). A significant rise in RDW in IDA 5-7 days after initiation of iron
      therapy (P = 0.00) which was continued to rise up to the 4(th) week of therapy
      was suggested as an important tool in differentiation of IDA from deltabeta-TT.
      These observations could be kept in mind in the differential diagnosis of
      deltabeta-TT from beta-TT and IDA by determining the red blood cell count, red
      cell indices, and RDW only.

PMID- 11835329
TI  - Rh genotyping: avoiding false-negative and false-positive results among
      individuals of African ancestry.
AB  - High homology, variant alleles, and silent alleles have made the development of
      completely reliable genotyping assays for the RHD and RHC alleles difficult. An
      RHD pseudogene (RHDPsi) possessing a 37-bp insertion within exon 4 is common
      among serologically RhD-negative individuals of African descent and generates
      false-positive results in previously reported RhD genotyping assays. Genotyping
      RhC is problematic due to exon 2 homology between RHD and RHC; however, an RHC
      specific 109-bp insertion within intron 2 has been reported useful for
      genotyping. Primers flanking the exon 4 insertion point were used for detection
      of RHD and RHDPsi among a total of 231 serotyped individuals: 134 African
      American, 85 Caucasian, and 12 RhD serotype-negative/genotype-positive, D
      sensitized women. Primers flanking the RHC-specific intron 2 insertion were used
      to genotype 282 serotyped individuals (128 African American, 154 Caucasian) and
      were compared to RHC genotyping using the exon 1 RhC-specific nt48 cytosine
      polymorphism. Complete correlation was observed between genotyping with the
      RHDPsi primer pair and serotyping among 219 individuals and 10/12 previous RHD
      false-positive genotyping results were resolved. RHDPsi was detected in 19% (n =
      4/21) of RhD seronegative African Americans and 4.4% (n = 5/113) of RhD
      seropositive African Americans. When using the 109-bp intron 2 insertion for
      genotyping of RHC, a 23.9% (n = 11/46) false-negative rate was observed among
      African American RhCc serotyped heterozygotes. Utilization of the exon 1 nt48
      cytosine for indirect genotyping of RHC yielded a 7.2% (n = 4/55) and 56.3% (n =
      45/80) false-positive rate among Rhcc Caucasians and African Americans,
      respectively. We conclude that these additional reactions, though not sufficient
      alone, can be useful supplements to existing Rh genotyping assays.

PMID- 11835330
TI  - Detection of relapse in non-Hodgkin's lymphoma: role of routine follow-up
      studies.
AB  - Complete remission can be achieved in 60-80% of adults with diffuse aggressive
      non-Hodgkin's lymphoma. However, 20-40% of them will subsequently relapse.
      Nevertheless, formal follow-up guidelines for recurrence detection have never
      been advocated. We analyzed the pattern of relapse in 30 patients with
      intermediate- and high-grade non-Hodgkin's lymphoma and the value of intensive
      protocol for relapse detection. This protocol includes frequent follow-up visits,
      complete blood count, and serum LDH tests along with annual chest, abdominal, and
      pelvic CT scans. The median duration of complete remission was 12 months. Twenty
      five relapses (83%) were suspected after an interim history and/or physical
      examination, whereas only 5 relapses (17%) were detected by routine radiographic
      or laboratory follow-up studies. The majority of relapses (19/30) were detected
      in sites that included the sites of prior disease. For the first 12 months of
      complete remission, the estimated cumulative save in charge for a follow-up
      strategy, based on regular visits in the hematology clinic and performing
      laboratory and radiologic studies as clinically indicated, is 44% of the cost of
      a routine intensive evaluation. A reliable and cost-effective follow-up method
      for non-Hodgkin's lymphoma patients in complete remission should include frequent
      history and physical examination. Complementary studies should be performed
      according to clinical indications.

PMID- 11835331
TI  - Hypothermia-induced platelet aggregation in heparinized flowing human blood:
      identification of a high responder subpopulation.
AB  - Cold-induced platelet aggregation (CIPA) in PRP has previously been documented in
      connection with platelet preservation (4-15 degrees C). This report describes
      hypothermia-induced platelet aggregation (HIPA) in whole blood and at
      temperatures used in open-heart surgery (24-32 degrees C). HIPA (specifically,
      the formation of occlusive aggregates) was studied in human whole blood. Fresh
      heparinized (1.5 U/ml) human blood was cooled and maintained at target
      temperatures (15, 20, 24, 28, 32, or 37 degrees C) as it flowed (1 ml/min)
      through 75-cm long 1/32 inches internal diameter polymer conduit. The formation
      of aggregates in the tubing was verified using optical video microscopy and was
      quantified by a light-scattering method and a constant-pressure filtration
      method. Donors were tested at least twice at each target temperature and were
      classified into three separate response regimes (Low, Medium, and High) on the
      basis of the number of aggregates and the duration of their appearance. The
      screening of 121 donors (average age 22.3 +/- 4.3 years) for HIPA at 24 degrees C
      (the temperature of maximum response) indicated 14% High Responders, 18% Medium
      Responders, and 68% Low Responders. HIPA was inhibited by EDTA, citrate, PGE1,
      and Tirofiban, but not by aspirin, and it was enhanced by elevated heparin
      levels. HIPA was consistently noted in the blood of a subpopulation of donors,
      and the associated platelet aggregates in the blood of High Responders were rigid
      and occlusive. It is postulated that such aggregates may contribute to cognitive
      dysfunction noted in patients undergoing hypothermic open-heart surgery, and that
      postulus is being investigated.

PMID- 11835333
TI  - Clonal evolution of blasts in an elderly patient with CD56(+) relapsed acute
      promyelocytic leukemia.
AB  - We describe an elderly patient with acute promyelocytic leukemia (APL), whose
      leukemic cells expressed CD56 antigen at relapse but not at diagnosis. Chromosome
      analysis revealed that blasts with t(8;15;17)(q24.1;q22;q11.2) increased from 4
      of 20 cells (20%) at first relapse to 10 of 14 cells (71.4%) at second relapse.
      In addition, the positivity for CD56 expression on blasts judged by flow
      cytometric analysis using CD45 blast gating was also increased from 14.2% at
      first relapse to 75% at second relapse. Although conventional chemotherapy was
      performed for the initial disease and the first relapse, relapse developed again.
      Therefore, three courses of intensive postremission chemotherapy including
      concurrent administration of recombinant human granulocyte colony-stimulating
      factor (rhG-CSF) with cytarabine were performed after achievement of complete
      remission (CR) by the treatment with all-trans-retinoic acid (ATRA). Although PML
      RARalpha mRNA was not detectable by reverse transcription polymerase chain
      reaction (RT-PCR), a third relapse occurred. This case demonstrated clonal
      evolution from a CD56(-) to a CD56(+) blast population and provided further
      support for the suggestion that CD56 expression might be an unfavorable
      prognostic factor in t(15;17) APL.

PMID- 11835332
TI  - Early onset of acute immune-mediated lung injury in a child undergoing allogeneic
      peripheral blood transplantation.
AB  - Animal models have recently clarified the lung injury after allogeneic
      hematopoietic transplantation. These works have confirmed the role of donor T
      lymphocytes in immune-mediated inflammatory reactions in the lung. We report here
      a fatal case of a 3-year-old child who developed acute respiratory failure
      coinciding with the onset of hyper-acute graft versus host disease (aGVHD) after
      allogeneic peripheral stem cell transplantation. aGVHD was refractory to
      treatment and the patient died on day +28. Lung necropsy showed interstitial
      pneumonia and peribronchial and perivascular infiltration by mononuclear cells,
      with no viral inclusions. These findings are not specific but have been found by
      some authors in animal models with acute immune-mediated lung injury related with
      donor T lymphocytes. Immune-mediated lung injury, as defined by animal models,
      should be considered in patients with severe signs of systemic aGVHD while
      excluding other known etiologies of pulmonary disease.

PMID- 11835334
TI  - Autologous peripheral stem cell transplantation for aggressive hemophagocytic
      syndrome associated with T-cell lymphoma: case study and review.
AB  - Hemophagocytic syndrome (HPS) is a rare clinical presentation infrequently
      associated with lymphoproliferative disorders. We describe a 29-year-old male
      with aggressive HPS and T-cell lymphoma managed successfully with high-dose
      chemotherapy and autologous peripheral stem cell transplantation (APSCT), in
      remission at 41 months of follow-up. In reviewing the literature, this case
      illustrates the 2nd longest surviving individual post stem cell transplant for
      aggressive HPS.

PMID- 11835335
TI  - Treatment of sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman
      disease): report of a case and literature review.
AB  - Sinus histiocytosis with massive lymphadenopathy (SHML) is a rare disorder of
      unknown etiology, usually associated with lymph node enlargement in various
      superficial or deep sites. It usually shows a prolonged clinical course with
      occasional exacerbation and remission phases. We describe the long-term follow-up
      of a case of SHML that showed typical clinical features and in which various
      therapeutic strategies were attempted. Chemotherapy and alpha-interferon (IFN)
      were ineffective; surgery was ultimately required with satisfactory results. From
      an extensive literature review we found different treatment strategies in SHML in
      the 80 cases published between 1969 and 2000. Spontaneous resolution of
      adenopathies is frequently observed: 32 out of 40 cases which did not receive
      chemotherapy, radiotherapy, or surgery were healthy at the time of publication.
      Radiotherapy alone showed conflicting results: 3 complete remissions (CR) were
      obtained in the 9 patients treated. Surgical debulking when required was
      effective--8/9 CR--while chemotherapy showed generally negative results. IFN has
      been previously employed in only one case. In conclusion, clinical observation
      without treatment is advisable when possible. In the presence of vital organ
      compression and/or extranodal localization with important clinical signs,
      surgical debulking may be necessary. Radiotherapy has shown limited efficacy,
      while chemotherapy is in general ineffective. More experience is needed to
      evaluate the role of IFN.

PMID- 11835336
TI  - Frequency of anti-heparin-platelet factor 4 antibodies in hemodialysis patients
      and correlation with recurrent vascular access thrombosis.
AB  - Heparin-induced thrombocytopenia (HIT), characterized by the formation of
      antibodies to a complex of platelet factor 4 (PF4) and heparin, is a well
      recognized risk factor for thromboembolic complications. The frequency of
      antibody development varies among patient populations. Hemodialysis patients have
      repeated heparin exposure and should be at risk of developing HIT. This might,
      contribute to the development of vascular access thrombosis. We prospectively
      evaluated 88 hemodialysis patients for the presence of anti-PF4/heparin
      antibodies. Eighteen patients (20%) had a prior history of 1 or more prior access
      thrombosis. One patient (1.14%), without a history of graft thrombosis, tested
      positive for anti-PF4/heparin antibodies. In our study, the presence of anti
      PF4/heparin antibodies was rare and was not increased in patients with a history
      of vascular access thrombosis.

PMID- 11835337
TI  - Mutation of bcl-x gene in non-Hodgkin's lymphoma.
AB  - The bcl-x gene product has two forms, bcl-xl and bcl-xs. The bcl-xl form, similar
      to bcl-2, inhibits apoptosis. Reverse transcriptase-polymerase chain
      reaction/single-stranded conformation polymorphism (RT-PCR-SSCP) gel analysis was
      used to screen for mutations of the bcl-xl transcript of 50 non-Hodgkin's
      lymphoma (NHL) cases. One missense mutation in a patient with diffuse large B
      cell lymphoma was found. Sequence analysis of this case showed that AGC (Ser) was
      mutated to GGC (Gly) in codon 154. An examination of mutation and/or polymorphism
      in born marrow samples of this case and 50 normal controls by the RT-PCR-SSCP
      method could not detect bandshifts. Mutation of the bcl-x gene in NHL has not
      been reported previously. There is a possibility that mutation of the bcl-x gene
      play a role in the tumorigenesis of NHL.

PMID- 11835338
TI  - Study of the single nucleotide polymorphism (SNP) at the palindromic sequence of
      hypersensitive site (HS)4 of the human beta-globin locus control region (LCR) in
      Indian population.
AB  - LCR, a genetic regulatory element, was examined in beta-thalassemia patients who
      do not show any mutation in the beta-globin genes. We sequenced LCR-HS2, HS3, and
      HS4 in samples from 16 such patients from the Indian population and found only
      one SNP A-G in the inverted repeat in HS4. A significant association was observed
      between the G allele and occurrence of beta-thalassemia by Fisher's exact test.
      The AG and GG genotypes showed higher relative risk as compared to the AA
      genotype. We also observed linkage disequilibrium between the A/G polymorphism
      and the AT-rich motif of the LCR HS2 region, suggesting that the G allele could
      be an evolutionarily new mutation in the study population.

PMID- 11835339
TI  - Expression of the TEL/EVI1 fusion transcript in a patient with chronic
      myelogenous leukemia with t(3;12)(q26;p13).
AB  - The t(3;12)(q26;p13) translocation is a recurrent chromosomal aberration observed
      in myeloid malignancies. It has been shown that the translocation results in the
      fusion of the TEL (ETV6) gene at 12p13 and the EV11 gene at 3q26. We report the
      first case with Philadelphia (Ph)-positive chronic myelogenous leukemia (CML)
      expressing the TEL/EVI1 fusion transcript. A 26-year-old man was initially
      diagnosed as having the chronic phase of Ph-positive CML. The t(3;12)(q26;p13)
      emerged 16 months prior to the myeloid blastic crisis. Reverse transcriptase
      polymerase chain reaction detected the TEL/EVI1 transcript without the
      intervening 5' non-coding exon of EVI1, suggesting that inappropriate expression
      of the EVI1 protein driven by the TEL promotor could play a critical role in
      progression to the blast crisis of CML.

PMID- 11835341
TI  - Elevated platelet-associated IgG in immune thrombocytopenic purpura associated
      with Waldenstrom's macroglobulinemia.

PMID- 11835340
TI  - Platelet glycoprotein Ia 807C/T (Phe224) and 873G/A (Thr246) dimorphisms in
      Turkey.
AB  - At sites of vascular injury, the platelet collagen receptor Glycoprotein Ia/IIa
      (GPIa/IIa) acts as an important mediator of platelet adhesion to fibrillar
      collagens. Two silent polymorphisms (807C/T and 873G/A) within the glycoprotein
      Ia gene have been implicated in increased risk of developing thrombosis and
      myocardial infarction in affected individuals. To provide basis for future
      studies, we examined the frequency of these GPIa polymorphisms for people in
      Turkey. We analyzed 118 unrelated individuals for their genotypes of the GPIa
      gene using a multiplexed allele specific-PCR based method. The allelic
      frequencies were found to be 34% for 807T/873A and 66% for 807C/873G; the
      genotypic frequencies were 13% for 807TT/873AA, 44% for 807CT/873GA, and 43% for
      807CC/873GG.

PMID- 11835342
TI  - Co-inheritance of Gilbert's syndrome and sickle cell anemia.

PMID- 11835343
TI  - Coagulation changes in individuals with sickle cell trait.
AB  - Sickle cell disorders, such as Hb SS and Hb SC, are associated with a
      hypercoagulable state that may contribute to the vaso-occlusive episodes observed
      in the disorders. To what extent increased coagulation activity occurs in
      individuals with sickle cell trait has had limited study. Because such
      information may help clarify clinical and pathologic findings that may occur in
      these individuals and may be useful in clarifying the hypercoagulable state in
      sickle cell disease, we have examined individuals with Hb AS to determine the
      extent that increased coagulation activity does occur. We measured d-dimers,
      thrombin-antithrombin (TAT) complexes, prothrombin fragment 1.2 (F1.2), absolute
      blood monocyte levels, proteins C and S, and isotypes of antiphospholipid
      antibodies in individuals with Hb AS and in matched controls (Hb AA). Results
      showed that d-dimers, TAT, and F1.2 were increased significantly above normal
      levels. Absolute blood monocyte levels were increased. The d-dimers, TAT, F1.2,
      and monocyte counts showed significant increasing trends through groups of
      increasing severity (Hb AA, Hb AS, Hb SC, and Hb SS). Our study shows that
      individuals with Hb AS have increased coagulation activity, with d-dimers, TAT,
      and F1.2 being consistent indicators. The measures of coagulation activity in Hb
      AS are lower than in patients with Hb SC and Hb SS disease. These results extend
      our previous observation that the degree of coagulation activation parallels the
      degree of disease severity among sickle cell genotypes. The findings suggest that
      monocytosis, with the possible expression of monocyte-derived tissue factor, and
      the associated hypercoagulable state are driven by disease severity.

PMID- 11835344
TI  - Fetal hemoglobin elevation in Hb Lepore heterozygotes and its correlation with
      beta globin cluster linked determinants.
AB  - We have analysed, at the hematological and molecular level, 51 Hb lepore
      heterozygotes and three compound heterozygotes for Hb Lepore and HbS (HbLep/HbS)
      in 26 unselected Portuguese families. The Lepore Boston variant was present in
      one family, in association with classical haplotype V. All of the other Lepore
      alleles present haplotype III in association with XmnI (+)5' of (G)gamma gene, in
      tight linkage disequilibrium to the major mutation found in the Portuguese
      population, the Lepore Baltimore variant ( delta(68Leu)-beta(84Thr)). The three
      compound heterozygotes are the first HbLep/HbS individuals reported in the
      literature, with the Lepore Baltimore mutation linked to haplotype III. In
      agreement with other studies, these Lepore Baltimore heterozygotes have higher
      HbF (1.4-14.1% of total hemoglobin) than published cases of Lepore Boston (0.8
      5.4%), which is associated with XmnI(-). Among the Lepore Baltimore
      heterozygotes, the (AT)xTy repeat region at -540 bp of the beta globin gene in
      trans to the Lepore chromosome, can account for much of the variability in HbF
      level. The allele (AT)7T7 is associated with lower HbF, and (AT)9T5 is associated
      with higher HbF. As we previously reported for beta thalassemic carriers, we
      observe in Lepore Baltimore carriers an effector in trans, linked to the (AT)xTy
      sequence, acting as an HPFH (Hereditary Persistence of Fetal Hemoglobin)
      determinant.

PMID- 11835345
TI  - Central venous catheter complications in sickle cell disease.
AB  - A review of patients with sickle cell disease (SCD) and central venous catheters
      (CVCs) was performed to evaluate the frequency of catheter complications
      (infections, thrombotic events, and premature CVC removal. Fifteen evaluable
      patients were identified during our review of a 7.5-year period. The median age
      was 18 years (range, 1.5-30 years); 14 were African American, and 1 was Latino; 5
      were male, and 10 were female. Forty-one CVCs were placed (36 Mediport and 5
      Broviac catheters) for a total of 12,120 CVC days. We observed a median of 2 CVCs
      per patient (range, 1-8 CVCs per patient) with 67 discrete episodes of CVC
      associated infection (range, 0-18 per patient) involving 10 patients. The rate of
      CVC-associated infection for patients with SCD at our institution was 5.5
      infections per 1,000 CVC days; this rate was significantly higher than the rate
      of CVC-associated infection in our patients with cancer (P < 0.001). We also
      determined that the rate of CVC-associated thrombosis was 0.99 events per 1,000
      CVC days and involved 33% of the patients with SCD; the rate of premature CVC
      removal was 3.15 per 1,000 CVC days, and 78% of CVCs were removed prematurely. We
      conclude that patients with SCD are at high risk for CVC-related complications,
      and improved care and close monitoring of CVCs should be encouraged to decrease
      morbidity in these chronically ill patients.

PMID- 11835346
TI  - Patterns of low-affinity immunoglobulin receptor polymorphisms in stroke and
      homozygous sickle cell disease.
AB  - Symptomatic stroke is a major complication of homozygous sickle cell (SS)
      disease, with a prevalence of approximately 10%. An elevated peripheral leukocyte
      count has been identified as a risk factor for hemorrhagic stroke in adults with
      SS disease. It has been observed that sickle cells coated with immunoglobulin
      have increased adherence to endothelial cells or phagocytes, possibly via binding
      to the low-affinity Fcgamma receptors. Common polymorphisms have been described
      in three low-affinity receptors: FCGR2A, FCGR3A, and FCGR3B; each has been shown
      to alter biological function, and each has also been associated with disease
      susceptibility. On the basis of this information, we evaluated common genetic
      variants of the low-affinity Fcgamma receptors for an association with
      symptomatic stroke in SS disease in a pilot case-control study of 51 Jamaican
      adult SS disease stroke cases and 51 SS disease-matched controls. Comparison of
      allelic distributions between cases and controls at 3 loci, FCGR2A (P = 0.39),
      FCGR3A (P = 0.67), FCGR3B (P = 0.35), failed to demonstrate a significant
      association. In a separate analysis, the FCGR2A/FCGR3A two-locus combination does
      not appear to segregate randomly (P(COR) = 0.0053), suggesting that these two
      loci could be linked in this population. We conclude that polymorphisms of the
      low-affinity Fcgamma receptors are not associated with stroke in SS disease.

PMID- 11835347
TI  - Normal outcome of pregnancy in chronic myeloid leukemia treated with interferon
      alpha in 1st trimester: report of 3 cases and review of the literature.
AB  - Three patients with chronic myeloid leukemia (CML) in chronic phase received
      interferon-alpha during pregnancy, starting from the 1st trimester. No maternal
      complications were reported. The 3 patients delivered normal looking babies apart
      from one baby who was found to have transient mild thrombocytopenia. Subsequently
      these children were followed for 30, 12, and 4 months and all had normal growth
      and development.

PMID- 11835349
TI  - Radiation therapy and combination of cladribine, cyclophosphamide, and prednisone
      as treatment of Bing-Neel syndrome: Case report and review of the literature.
AB  - Waldenstrom's macroglobulinemia is a low-grade lymphoma that produces monoclonal
      IgM. Central nervous system symptoms are frequent in Waldenstrom's
      macroglobulinemia, mostly associated with blood hyperviscosity. Nevertheless,
      central nervous system infiltration by malignant cells (Bing-Neel syndrome) has
      rarely been reported. We describe the case of a 72-year-old man with
      Waldenstrom's macroglobulinemia and central nervous system infiltration by
      malignant cells with tumor formation. All similar cases reported in the
      literature are reviewed and the different therapeutic approaches discussed.

PMID- 11835348
TI  - Castleman's disease and lymphoma: report of eight cases in HIV-negative patients
      and literature review.
AB  - Castleman's disease (CD) is a rare atypical lymphoproliferative disorder
      associated with a risk of developing malignant lymphoma. We have recorded 8 HIV
      negative patients presenting this association, 6 with non-Hodgkin's lymphoma
      (NHL) and 2 with Hodgkin's disease (HD). After literature review, we analyzed all
      reported cases of association CD-NHL (n = 23) and CD-HD (n = 27). NHL is more
      often associated with multicentric CD, its diagnosis being concurrent with CD
      diagnosis or occurring within 2 years. B-NHL is predominant (71%), and mantle
      cell lymphoma represents 40% of these B-NHL cases. NHL displays an aggressive
      course and is liable for death, especially in multicentric CD. HD occurs in
      localized CD of plasma cell type, usually in the same areas, is more often of
      interfollicular subtype, and its clinical course seems better than NHL. The
      association of CD and lymphoma seems to be more than coincidental, and its
      pathogenesis is discussed.

PMID- 11835350
TI  - T-gamma large granular lymphocyte leukemia associated with amegakaryocytic
      thrombocytopenic purpura, Sjogren's syndrome, and polyglandular autoimmune
      syndrome type II, with subsequent development of pure red cell aplasia.
AB  - We present a female patient with T-gamma LGL leukemia, who was followed for the
      last 20 years. Over these years she developed several autoimmune disorders,
      including Sjogren's syndrome, Hashimoto's thyroiditis, premature ovarian failure
      (compatible with type II autoimmune polyglandular syndrome), amegakaryocytic
      thrombocytopenic purpura, and finally pure red cell aplasia. PCR analysis
      confirmed rearrangement for TCR gamma. This case emphasizes the complex
      association of LGL leukemia with autoimmune disorders.

PMID- 11835351
TI  - Inverse relationship between plasma von Willebrand factor and soluble P selectin
      in patients with type 1 but not type 2 von Willebrand disease.
AB  - P selectin is a component of endothelial Wiebel-Palade body membrane and platelet
      alpha granule membrane. Patients with von Willebrand disease (VWD) have low
      plasma von Willebrand factor (VWF). To examine the relationship between plasma P
      selectin and VWF, both were measured by ELISA in 38 patients with VWD and 40
      controls. The patient had lower VWF (P < 0.001) but similar P selectin levels (P
      = 0.458). In 24 type 1 VWD patients, VWF and P selectin correlated inversely (P =
      0.005) but in 14 type 2 VWD patients there was no correlation (P = 0.997). These
      data imply major differences in VWF/P-selectin regulation between types 1 and 2
      VWD.

PMID- 11835352
TI  - Granulocyte-colony stimulating factor enhances the expression of transforming
      growth factor-beta mRNA in CD4-positive peripheral blood lymphocytes in the
      donors for allogeneic peripheral blood stem cell transplantation.
AB  - The degree of acute graft-versus-host disease (GVHD) after allogeneic peripheral
      blood stem cell transplantation (allo-PBSCT) has been observed to be,
      unexpectedly, of an equal level to that after bone marrow transplantation. To
      explain this phenomenon, we hypothesized that granulocyte-colony stimulating
      factor (G-CSF) administration may induce transforming growth factor (TGF)-beta
      producing T cells in the donors. Five donors received 10 microg/kg G-CSF
      subcutaneously for 4 days. The TGFbeta mRNA expression in CD4(+) cells as
      measured by real time reverse transcription-polymerase chain reaction increased
      after G-CSF administration. This elevation is considered to be one additive
      mechanism of repression of acute GVHD after allo-PBSCT.

PMID- 11835353
TI  - Expression and sequence analyses of p33(ING1) gene in myeloid leukemia.
AB  - p33(ING1) is a novel candidate tumor suppressor gene which is involved in the
      regulation of apoptosis. p33(ING1) interacts with p53 signaling pathway and
      regulates cellular growth. It has reported that the expression of p33(ING1) mRNA
      was decreased in lymphoid malignancies. We thus investigated the potential
      involvement of p33(ING1) abnormalities in myeloid leukemias. However, the levels
      of p33(ING1) transcript were almost equal in 3 AML cell lines and 10 fresh AML
      samples. In addition, neither point mutations nor deletions in p33(ING1) gene
      were found in myeloid leukemias. These results suggest that p33(ING1) may not be
      a major candidate tumor suppressor gene in myeloid leukemias.

PMID- 11835354
TI  - Reduced vitamin E antioxidant capacity in sickle cell disease is related to
      transfusion status but not to sickle crisis.
AB  - In homozygous sickle cell disease (SCD), decreased serum Vitamin E is present.
      Excessive transfusions may lead to iron overload. We hypothesised a relationship
      between the two and found that Vitamin E type antioxidant capacity was
      significantly lower in 30 SCD patients than in 30 age- and sex-matched controls
      (P < 0.001). Antioxidant capacity was lower in 10 transfused patients compared
      with 20 non-transfused patients (P < 0.001). Transfusional iron overload in SCD
      may increase the potential for oxidative damage, and low antioxidant capacity may
      compound this effect.

PMID- 11835355
TI  - CD5-negative phenotype of monoclonal B-lymphocytosis of undetermined significance
      (MLUS).
AB  - Monoclonal B lymphocytosis of undetermined significance (MLUS) is a benign
      condition of clonal lymphocytosis. Because of its clonal small lymphocytes and
      indolent clinical course, MLUS resembles and may be indistinguishable from an
      early stage of chronic lymphocytic leukemia (CLL). In this study we characterized
      the immunophenotype of MLUS. The clonal B lymphocytes from three patients of
      typical MLUS were shown to be CD5(-) and CD23(-) phenotype. Their
      immunophenotypic features remained unchanged during the clinical course. The
      results indicate a distinct immunophenotype of MLUS that can be useful for its
      diagnosis and differentiation from CLL.

PMID- 11835356
TI  - Systemic anaplastic large cell lymphoma in a child presenting with bone marrow
      involvement and clinical features of acute leukaemia.

PMID- 11835357
TI  - Lamivudine therapy for acute hepatitis B infection following peripheral blood
      stem cell transplantation.

PMID- 11835358
TI  - Unusual case of coronary artery disease in a patient with severe hemophilia B.

PMID- 11835359
TI  - Transient demyelinating neurologic lesions in a patient with idiopathic
      hypereosinophilic syndrome.

PMID- 11835361
TI  - Ontogenetic and phylogenetic transformations of the ear ossicles in marsupial
      mammals.
AB  - This study is based on the examination of histological sections of specimens of
      different ages and of adult ossicles from macerated skulls representing a wide
      range of taxa and aims at addressing several issues concerning the evolution of
      the ear ossicles in marsupials. Three-dimensional reconstructions of the ear
      ossicles based on histological series were done for one or more stages of
      Monodelphis domestica, Caluromys philander, Sminthopsis virginiae, Trichosurus
      vulpecula, and Macropus rufogriseus. Several common trends were found. Portions
      of the ossicles that are phylogenetically older develop earlier than portions
      representing more recent evolutionary inventions (manubrium of the malleus, crus
      longum of the incus). The onset of endochondral ossification in the taxa in which
      this was examined followed the sequence; first malleus, then incus, and finally
      stapes. In M. domestica and C. philander at birth the yet precartilaginous
      ossicles form a supportive strut between the lower jaw and the braincase. The
      cartilage of Paauw develops relatively late in comparison with the ear ossicles
      and in close association to the tendon of the stapedial muscle. A feeble artery
      traverses the stapedial foramen of the stapes in the youngest stages of M.
      domestica, C. philander, and Sminthopsis virginiae examined. Presence of a large
      stapedial foramen is reconstructed in the groundplan of the Didelphidae and of
      Marsupialia. The stapedial foramen is absent in all adult caenolestids,
      dasyurids, Myrmecobius, Notoryctes, peramelids, vombatids, and phascolarctids.
      Pouch young of Perameles sp. and Dasyurus viverrinus show a bicrurate stapes with
      a sizeable stapedial foramen. Some didelphids examined to date show a double
      insertion of the Tensor tympani muscle. Some differences exist between M.
      domestica and C. philander in adult ossicle form, including the relative length
      of the incudal crus breve and of the stapes. Several differences exist between
      the malleus of didelphids and that of some phalangeriforms, the latter showing a
      short neck, absence of the lamina, and a ventrally directed manubrium. Hearing
      starts in M. domestica at an age in which the external auditory meatus has not
      yet fully developed, the ossicles are not fully ossified, and the middle ear
      space is partially filled with loose mesenchyme. The ontogenetic changes in
      hearing abilities in M. domestica between postnatal days 30 and 40 may be at
      least partially related to changes in middle ear structures.

PMID- 11835362
TI  - The sensory epithelium of the tentacles and the rhinophore of Nautilus pompilius
      L. (cephalopoda, nautiloidea).
AB  - Nine intraepithelial ciliated cell types that are presumed to be sensory cells
      were identified in the epithelium of the pre- and postocular tentacles, the
      digital tentacles, and the rhinophore of the juvenile tetrabranchiate cephalopod
      Nautilus pompilius L. The morphological diversity and specialization in
      distribution of the different ciliated cell types analyzed by SEM methods suggest
      that these cells include receptors of several sensory functions. Ciliated cell
      types in different organs that show similar surface features were combined in
      named groups. The most striking cell, type I, is characterized by a tuft of long
      and numerous cilia. The highest density of this cell type occurs in ciliary
      fields in the epithelium of the lamellae of the pre- and postocular tentacles, in
      the olfactory pits of the rhinophores, and in the lamellae of four pairs of
      lateral digital tentacles, but not in the epithelium of the medial digital
      tentacles. The similar morphological data, together with behavioral observations
      on feeding habits, suggest that this cell type may serve in long-distance
      chemosensory function. The other ciliated cell types are solitary cells with
      specific spatial distributions in the various organs. Cell types with tufts of
      relatively short, stiff cilia (types III, IV, VIII), which are distributed in the
      lateral and aboral areas of the tentacles and at the base of the tentacle-like
      process of the rhinophore, are considered to be employed in mechanosensory
      transduction, while the solitary cells with bristle-like cilia at the margin of
      the ciliary fields (type II) and at the base of the rhinophore (type IX) may be
      involved in chemoreception. Histological investigation of the epithelium and the
      nerve structures of the different organs shows the proportion and distribution of
      the sensory pathways. Two different types of digital tentacles can be
      distinguished according to their putative functions: lateral slender digital
      tentacles in four pairs, of which the lowermost are the so-called long digital
      tentacles, participate in distance chemoreception, and the medial digital
      tentacles, whose terminal axial nerve cord may represent a specialized
      neuromechanosensory structure, appear to have contact chemoreceptive abilities.

PMID- 11835363
TI  - Muscular anatomy of the millipede Phyllogonostreptus nigrolabiatus (Diplopoda:
      Spirostreptida) and its bearing on the millipede "thorax".
AB  - The muscular anatomy of the millipede Phyllogonostreptus nigrolabiatus (Newport,
      1844) (Diplopoda; Spirostreptida; Harpagophoridae) is comprehensively surveyed.
      The musculature of the first three postcollum pleurotergites, the "thorax," and
      their associated appendages was found to be more complex than that of the
      postthoracic rings. It is hypothesized that the musculature of the postthoracic
      segments is derived relative to that of the thoracic segments, which retain
      primitively free sternites and are not diplosegments. This hypothesis is
      discussed relative to previous hypotheses positing that the anteriormost three
      leg-bearing rings in millipedes are diplosegments. The musculature of
      spirostreptid gonopods is described in detail for the first time. Comparison of
      the cephalic musculature is made with previously described musculature in Julida
      showing that, while many aspects of the musculature are conserved, there exist
      interordinal differences, documenting the potential utility of comparative
      anatomical studies for resolving millipede phylogeny.

PMID- 11835364
TI  - Gut-associated cells of Derocheilocaris remanei (Crustacea, Mystacocarida).
AB  - The gut-associated cells (GA-cells) of the mystacocarid Derocheilocaris remanei
      were investigated by transmission electron microscopy. These cells are
      characterized by a dense cytoplasm, the presence of clear vesicles adjacent to
      the gut epithelium, glycogen, and lipid droplets. GA-cells envelop the midgut and
      hindgut and send blunt cytoplasmic extensions to the gut epithelium through its
      basal lamina. The GA-cells also extend dorsolateral projections to the body wall
      by means of intermediate cells. In addition to a mechanical function of
      suspending and stabilizing the gut, these cells may affect the flow of the
      hemocoelic fluid and may be implicated in the processes of transport,
      assimilation, and storage of nutrients.

PMID- 11835365
TI  - Avian furcula morphology may indicate relationships of flight requirements among
      birds.
AB  - This study examined furcula (wishbone) shape relative to flight requirements. The
      furculae from 53 museum specimens in eight orders were measured: 1) three
      dimensional shape (SR) as indicated by the ratio of the direct distance between
      the synostosis interclavicularis and the ligamentous attachment of one of its
      clavicles to the actual length of the clavicle between those same two points, and
      2) curvature within the primary plane (LR) as indicated by the ratio of the
      length of the clavicle to the sum of the orthogonal distances between the same
      points using a projected image. Canonical discriminant analysis of these ratios
      placed the individuals into a) one of four general flight categories and b) one
      of eight taxonomic orders. The four flight categories were defined as: i) soaring
      with no flapping, ii) flapping with no soaring, iii) subaqueous (i.e., all
      wingbeats taking place under water), and iv) partial subaqueous (i.e., wingbeats
      used for both aerial and submerged flapping). The error rate for placement of the
      specimens in flight categories was only 26.4%, about half of the error rate for
      placement in taxonomic orders (51.3%). Subaqueous fliers (penguins, great auks)
      have furculae that are the most V-shaped. Partial subaqueous fliers (alcids,
      storm petrels) have furculae that are more U-shaped than the subaqueous fliers
      but more V-shaped than the aerial flapping fliers. The partial subaqueous fliers
      have furculae that are also the most anteriorly curved, possibly increasing
      protraction capability by changing the angle of applied force and increasing
      attachment area for the origin of the sternobrachialis pectoralis. The increased
      protraction capability can counteract profile drag, which is greater in water
      than in air due to the greater density of water. Soaring birds have furculae that
      are more U-shaped or circular than those of flapping birds and have the smallest
      range of variation. These results indicate that the shape of the furcula is
      functionally related to general differences in flight requirements and may be
      used to infer relationships of these requirements among birds.

PMID- 11835366
TI  - Keratinization and lipogenesis in epidermal derivatives of the zebrafinch,
      Taeniopygia guttata castanotis (Aves, Passeriformes, Ploecidae) during embryonic
      development.
AB  - Little is known of the lipid content of beta-keratin-producing cells such as
      those of feathers, scutate scales, and beak. The sequence of epidermal layers in
      some apteria and in interfollicular epidermis in the zebrafinch embryo
      (Taeniopygia guttata castanotis) was studied. Also, the production of beta
      keratin in natal down feathers and beak was ultrastructurally analyzed in embryos
      from 3-4 to 17-18 days postdeposition, before hatching. Two layers of periderm
      initially cover the embryo, but there are eventually 6-8 over the epidermis of
      the beak. In the beak and sheath cells of feathers, peridermal granules are
      numerous at 12-14 days postdeposition but they are less frequent in apteria.
      These granules swell and disappear during sheath or peridermal degeneration at 15
      17 days postdeposition. A thin beta-keratin layer forms under the periderm among
      feather germs of pterylous areas but is discontinuous or disappears in apteria.
      In differentiating cells of barbs, barbules, and calamus cells of natal down,
      electron-dense beta-keratin filaments form bundles oriented along the main axis
      of these cells. Cells of the pulp epidermis and collar, at the base of the
      follicle, contain lipids and bundles of alpha-keratin filaments. Degenerating
      pulp cells show vacuolization and nuclear pycnosis. During beta-keratin packing,
      keratin bundles turn electron-pale, perhaps due to the addition of lipids to
      produce the final, homogenous beta-keratin matrix. In contrast to the situation
      in feathers, in the cells of beak beta-keratin packets are irregularly oriented.
      In both feather and beak epidermal cells the Golgi apparatus and smooth
      endoplasmic reticulum produce vesicles containing lipid-like material which is
      also found among forming beta-keratin. The contribution of lipids or lipoprotein
      to the initial aggregation of beta-keratin molecules is discussed.

PMID- 11835367
TI  - Comparison of isometric contractile properties in hindlimb extensor muscles of
      the frogs Rana pipiens and Bufo marinus: functional correlations with differences
      in hopping performance.
AB  - The leopard frog (Rana pipiens) is an excellent jumper that can reach high take
      off velocities and accelerations. It is diurnal, using long, explosive jumps to
      capture prey and escape predators. The marine toad (Bufo marinus) is a cryptic,
      nocturnal toad, typically using short, slow hops, or sometimes walking, to patrol
      its feeding area. Typical of frogs with these different locomotor styles, Rana
      has relatively long hindlimbs and large (by mass) hindlimb extensor muscles
      compared to Bufo. We studied the isometric contractile properties of their
      extensor muscles and found differences that correlate with their different
      hopping performances. At the hip (semimembranosus, SM), knee (peroneus, Per) and
      ankle (plantaris longus, PL), we found that Rana's muscles tended to produce
      greater maximum isometric force relative to body mass, although the difference
      was significant only for PL. This suggests that differences in force capability
      at the ankle may be more important than at other joints to produce divergent
      hopping performances. Maximum isometric force scaled with body mass so that the
      smaller Rana has relatively larger muscles and force differences between species
      may reflect size differences only. In addition, Rana's muscles exhibited greater
      passive resistance to elongation, implying more elastic tissue is present, which
      may amplify force at take-off due to elastic recoil. Rana's muscles also achieved
      a higher percentage of maximum force at lower stimulus inputs (frequencies and
      durations) than in Bufo, perhaps amplifying the differences in force available
      for limb extension during natural stimulation. Twitch contraction and relaxation
      times tended to be faster in Rana, although variation was great, so that
      differences were significant only for Per. Fatigability also tended to be greater
      in Rana muscles, although, again, values reached significance in only one muscle
      (PL). Thus, in addition to biomechanical effects, differences in hopping
      performance may also be determined by diverse physiological properties of the
      muscles.

PMID- 11835368
TI  - Morphometry of Macaca mulatta forelimb. II. Fiber-type composition in shoulder
      and elbow muscles.
AB  - The present study examined the fiber-type proportions of 22 muscles spanning the
      shoulder and/or elbow joints of three Macaca mulatta. Fibers were classified as
      one of three types: fast-glycolytic (FG), fast-oxidative-glycolytic (FOG), or
      slow-oxidative (SO). In most muscles, the FG fibers predominated, but proportions
      ranged from 25-67% in different muscles. SO fibers were less abundant except in a
      few deep, small muscles where they comprised as much as 56% of the fibers. Cross
      sectional area (CSA) of the three fiber types was measured in six different
      muscles. FG fibers tended to be the largest, whereas SO fibers were the smallest.
      While fiber-type size was not always consistent between muscles, the relative
      size of FG fibers was generally larger than FOG and SO fibers within the same
      muscle. When fiber CSA was taken into consideration, FG fibers were found to
      comprise over 50% of the muscle's CSA in almost all muscles.

PMID- 11835369
TI  - Challenging assumptions about Alzheimer's disease: mild cognitive impairment and
      the cholinergic hypothesis.

PMID- 11835370
TI  - Upregulation of choline acetyltransferase activity in hippocampus and frontal
      cortex of elderly subjects with mild cognitive impairment.
AB  - In Alzheimer's disease (AD), loss of cortical and hippocampal choline
      acetyltransferase (ChAT) activity has been correlated with dementia severity and
      disease duration, and it forms the basis for current therapies. However, the
      extent to which reductions in ChAT activity are associated with early cognitive
      decline has not been well established. We quantified ChAT activity in the
      hippocampus and four cortical regions (superior frontal, inferior parietal,
      superior temporal, and anterior cingulate) of 58 individuals diagnosed with no
      cognitive impairment (NCI; n = 26; mean age 81.4 +/- 7.3 years), mild cognitive
      impairment (MCI; n = 18; mean age 84.5 +/- 5.7), or mild AD (n =14; mean age 86.3
      +/- 6.6). Inferior parietal cortex ChAT activity was also assessed in 12 subjects
      with end-stage AD (mean age 81.4 +/- 4.3 years) and compared to inferior parietal
      cortex ChAT levels of the other three groups. Only the end-stage AD group had
      ChAT levels reduced below normal. In individuals with MCI and mild AD, ChAT
      activity was unchanged in the inferior parietal, superior temporal, and anterior
      cingulate cortices compared to NCI. In contrast, ChAT activity in the superior
      frontal cortex was significantly elevated above normal controls in MCI subjects,
      whereas the mild AD group was not different from NCI or MCI. Hippocampal ChAT
      activity was significantly higher in MCI subjects than in either NCI or AD. Our
      results suggest that cognitive deficits in MCI and early AD are not associated
      with the loss of ChAT and occur despite regionally specific upregulation. Thus,
      the earliest cognitive deficits in AD involve brain changes other than simply
      cholinergic system loss. Of importance, the cholinergic system is capable of
      compensatory responses during the early stage of dementia. The upregulation in
      frontal cortex and hippocampal ChAT activity could be an important factor in
      preventing the transition of MCI subjects to AD.

PMID- 11835371
TI  - Dopaminergic modulation of cortical function in patients with Parkinson's
      disease.
AB  - Patients with idiopathic Parkinson's disease suffer not only from classic motor
      symptoms, but from deficits in cognitive function, primarily those subserved by
      the prefrontal cortex as well. The aim of the current study was to investigate
      the modulatory effects of dopaminergic therapy on neural systems subserving
      working memory and motor function in patients with Parkinson's disease. Ten
      patients with stage I and II Parkinson's disease were studied with functional
      magnetic resonance imaging, during a relatively hypodopaminergic state (ie, 12
      hours after a last dose of dopamimetic treatment), and again during a dopamine
      replete state. Functional magnetic resonance imaging was performed under three
      conditions: a working memory task, a cued sensorimotor task and rest. Consistent
      with prior data, the cortical motor regions activated during the motor task
      showed greater activation during the dopamine-replete state; however, the
      cortical regions subserving working memory displayed greater activation during
      the hypodopaminergic state. Interestingly, the increase in cortical activation
      during the working memory task in the hypodopaminergic state positively
      correlated with errors in task performance, and the increased activation in the
      cortical motor regions during the dopamine-replete state was positively
      correlated with improvement in motor function. These results support evidence
      from basic research that dopamine modulates cortical networks subserving working
      memory and motor function via two distinct mechanisms: nigrostriatal projections
      facilitate motor function indirectly via thalamic projections to motor cortices,
      whereas the mesocortical dopaminergic system facilitates working memory function
      via direct inputs to prefrontal cortex. The results are also consistent with
      evidence that the hypodopaminergic state is associated with decreased efficiency
      of prefrontal cortical information processing and that dopaminergic therapy
      improves the physiological efficiency of this region.

PMID- 11835372
TI  - Interferon-beta therapy for multiple sclerosis induces reciprocal changes in
      interleukin-12 and interleukin-10 production.
AB  - Interleukin-12 is critical to the pathogenesis of experimental autoimmune
      encephalomyelitis in multiple species. Interleukin-10, a dominant endogenous
      inhibitor of interleukin-12, is largely protective in these experimental
      surrogates for multiple sclerosis. Such data have suggested that an interleukin
      12/interleukin-10 immunoregulatory circuit is a key determinant of disease
      expression in experimental autoimmune encephalomyelitis. For multiple sclerosis
      itself, compatible cytokine data have been reported. The mechanisms underlying
      the beneficial effects of interferon-beta in multiple sclerosis remain unclear,
      hampering the search for more effective therapies. Of note, interferon-beta has
      reciprocal effects on these cytokines in vitro, suppressing interleukin-12 and
      augmenting interleukin-10 production. To examine the effects of interferon-beta
      on the interleukin-12/interleukin-10 axis in multiple sclerosis, we characterized
      the production of these cytokines by peripheral blood mononuclear cells from
      patients beginning therapy with interferon-beta. Before therapy, multiple
      sclerosis patients exhibited increased stimulatable interleukin-12 production
      compared with controls. Interferon-beta therapy leads to inhibition of
      interleukin-12 and augmentation of interleukin-10 production, significantly
      elevating the ratio of secreted interleukin-10 to interleukin-12. These effects,
      observed equally in patients with relapsing-remitting and progressive disease,
      indicate that interferon-beta affects the interleukin-12/interleukin-10 axis in
      ways thought to be beneficial to multiple sclerosis patients. More specific
      therapeutic targeting of these pathways may be warranted.

PMID- 11835373
TI  - Phenobarbital and MK-801, but not phenytoin, improve the long-term outcome of
      status epilepticus.
AB  - To examine the effect of therapy on status epilepticus (SE) acutely and on long
      term outcome, we compared three drugs with three different mechanisms.
      Phenobarbital, MK-801, and phenytoin were administered at 1, 2, and 4 hours after
      initiation of limbic status epilepticus by "continuous" hippocampal stimulation
      in rats. We evaluated the effects of these drugs on the course of SE and the
      subsequent development of chronic epilepsy. Phenobarbital and MK-801 were
      superior to phenytoin in suppressing SE and in preventing chronic epilepsy. There
      was no benefit if treatment was given 2 hours after the initiation of SE.
      Phenobarbital was most effective in suppressing electrographic seizure activity,
      but MK-801 had a slightly wider window for the prevention of chronic epilepsy.
      Early treatment, rather than electrographic suppression of SE, correlated with
      prevention of chronic epilepsy. This study shows that the drugs administered,
      which have different mechanisms of action, have clear differences in altering the
      outcomes. The findings suggest that studies of SE treatment should examine the
      effect of therapy on SE itself, as well as the long-term benefits of each
      treatment. The use of N-methyl-D-aspartate receptor antagonists should be
      considered early in the treatment of SE.

PMID- 11835374
TI  - Parahippocampal tau pathology in healthy aging, mild cognitive impairment, and
      early Alzheimer's disease.
AB  - Abnormally phosphorylated tau accumulates as neurofibrillary tangles and neuropil
      threads in older persons with and without Alzheimer's disease. The relationship
      between neurofibrillary tangles and neuropil threads and how they relate to
      cognitive function is unknown. This study investigated the relationship between
      phosphorylated tau lesions and cognitive function in 31 persons participating in
      the Religious Orders Study, a prospective, longitudinal clinicopathological study
      of aging and Alzheimer's disease. All subjects underwent detailed
      neuropsychological performance testing within a year of death and evidenced a
      spectrum of cognitive performance ranging from normal abilities to mild dementia.
      Measures of neurofibrillary tangle density and phosphorylated tau immunoreactive
      structures (predominantly neuropil threads) in the entorhinal and perirhinal
      cortices by quantitative image analysis were significantly correlated (r = 0.5).
      In multiple linear regression analyses controlling for age, sex, and education,
      parahippocampal neurofibrillary tangles and neuropil threads were significantly
      lower in persons without cognitive impairment compared to those with mild
      cognitive impairment and/or Alzheimer's disease. Further, neurofibrillary tangles
      were significantly correlated to measures of episodic memory but not other
      cognitive abilities; neuropil tangles were not significantly related to memory or
      other cognitive functions. These data indicate that phosphorylated tau pathology
      in the ventromedial temporal lobe develop prior to the onset of clinical dementia
      and their presence is associated with cognitive impairment, particularly
      impairment of episodic memory.

PMID- 11835376
TI  - Insular cortex involvement in mesiotemporal lobe epilepsy: a positron emission
      tomography study.
AB  - Somesthetic and emotional symptoms that are common in patients with mesial
      temporal lobe epilepsy are usually related to hippocampo-amygdalar complex
      involvement. Recent stereo-electroencephalographic studies have shown a
      relationship between such symptoms and epileptic insular discharges. To further
      investigate this problem, we carried out a positron emission tomography study
      using fluorodeoxyglucose (18F-FDG) and flumazenil (11C-FMZ) in mesial temporal
      lobe epilepsy patients. The aim of our study was to assess the existence of a
      cortical insular involvement in order to examine its clinical correlates and the
      relationship between the postoperative outcome and the insular involvement.
      Fluorodeoxyglucose and flumazenil-positron emission tomography studies were
      carried out in 18 patients with mesial temporal lobe epilepsy patients. A
      statistical parametric mapping (SPM96) was performed to analyze the data in
      comparison to 18 healthy volunteers. For each set of fluorodeoxyglucose and
      flumazenil images a group and an individual analysis were performed. In addition,
      a region of interest analysis was performed to validate the results. Focusing on
      the metabolic abnormalities, we also investigated the role of insular cortex in
      the symptoms experienced by the patients and the prognostic value of insular
      metabolic abnormalities. Highly significant hypometabolism and BZR binding
      decreases were detected in the insular cortex. Results were similar using the
      region of interest approach. Insular involvement (mainly ipsilateral to the
      seizure focus) was present in 60% of the patients. Emotional symptoms correlated
      with hypometabolism in the anterior part of the ipsilateral insular cortex,
      whereas somesthetic symptoms correlated with hypometabolism in the posterior
      part. No relationship between postoperative outcome and ipsilateral insular
      hypometabolism was found. Unilateral mesial temporal lobe epilepsy is associated
      with insular hypometabolism and benzodiazepine receptor loss. Our results also
      suggest that the anterior part of the insular cortex is involved in the emotional
      symptoms and the posterior insular cortex is involved in the somesthetic
      symptoms. Hypometabolism located in the insula did not influence postoperative
      outcome after anterior lobectomy.

PMID- 11835375
TI  - Charcot-Marie-Tooth disease and related neuropathies: mutation distribution and
      genotype-phenotype correlation.
AB  - Charcot-Marie-Tooth disease (CMT) is a genetically heterogeneous disorder that
      has been associated with alterations of several proteins: peripheral myelin
      protein 22, myelin protein zero, connexin 32, early growth response factor 2,
      periaxin, myotubularin related protein 2, N-myc downstream regulated gene 1
      product, neurofilament light chain, and kinesin 1B. To determine the frequency of
      mutations in these genes among patients with CMT or a related peripheral
      neuropathy, we identified 153 unrelated patients who enrolled prior to the
      availability of clinical testing, 79 had a 17p12 duplication (CMT1A duplication),
      11 a connexin 32 mutation, 5 a myelin protein zero mutation, 5 a peripheral
      myelin protein 22 mutation, 1 an early growth response factor 2 mutation, 1 a
      periaxin mutation, 0 a myotubularin related protein 2 mutation, 1 a neurofilament
      light chain mutation, and 50 had no identifiable mutation; the N-myc downstream
      regulated gene 1 and the kinesin 1B gene were not screened for mutations. In the
      process of screening the above cohort of patients as well as other patients for
      CMT-causative mutations, we identified several previously unreported mutant
      alleles: two for connexin 32, three for myelin protein zero, and two for
      peripheral myelin protein 22. The peripheral myelin protein 22 mutation W28R was
      associated with CMT1 and profound deafness. One patient with a CMT2 clinical
      phenotype had three myelin protein zero mutations (I89N+V92M+I162M). Because one
      third of the mutations we report arose de novo and thereby caused chronic
      sporadic neuropathy, we conclude that molecular diagnosis is a necessary adjunct
      for clinical diagnosis and management of inherited and sporadic neuropathy.

PMID- 11835377
TI  - Accelerated hippocampal atrophy in Alzheimer's disease with apolipoprotein E
      epsilon4 allele.
AB  - Although apolipoprotein E epsilon4 is an established risk factor for Alzheimer's
      disease, its effect on the rate of progression of Alzheimer's disease remains
      unknown. The purpose of this longitudinal study was to elucidate whether the rate
      of hippocampal atrophy is a function of the apolipoprotein E genotypes and
      severity of disease. Fifty-five patients with probable Alzheimer's disease were
      the subjects. The annual rate of hippocampal atrophy was determined by using
      magnetic resonance imaging repeated at a 1-year interval. On a two-way analysis
      of variance, the effect of the apolipoprotein E epsilon4 allele on hippocampal
      atrophy was significant, but neither the effect of severity nor the interaction
      term was significant. In further analysis with one-way analysis of variance, the
      mean annual rate of hippocampal atrophy was significantly different between the
      groups of patients with (9.76 +/- 4.27%) and without the apolipoprotein E
      epsilon4 allele (6.99 +/- 4.24%). Apolipoprotein E epsilon4 dose was
      significantly correlated with the rate of hippocampal atrophy (rs = 0.277,
      Spearman rank correlation coefficient), suggesting a gene dose effect. The
      involvement of the apolipoprotein E epsilon4 allele in the progression of
      hippocampal atrophy has implications for therapeutic approaches in Alzheimer's
      disease and should be taken into consideration in longitudinal studies including
      clinical drug trials.

PMID- 11835378
TI  - Inhibition of autoimmune encephalomyelitis by a tetracycline.
AB  - We have explored the use of minocycline, a tetracycline with antiinflammatory
      properties, to treat chronic relapsing-remitting experimental allergic
      encephalomyelitis, an animal model of multiple sclerosis. Therapeutic treatment
      with minocycline dramatically suppresses ongoing disease activity and limits
      disease progression. Disease suppression is associated with immune deviation in
      the periphery and with suppression of the inflammatory cascade in the central
      nervous system. This association is demonstrated by inhibition of microglial
      activation and metalloproteinase-2 expression, which results in a concomitant
      decrease in inflammation and demyelination. As an established antiinflammatory
      drug with neuroprotective properties, minocycline may provide a novel therapeutic
      agent for relapsing-remitting multiple sclerosis.

PMID- 11835379
TI  - Familial cardioneuromyopathy with hyaline masses and nemaline rods: a novel
      phenotype.
AB  - Two siblings (patients 1 and 2) had adult-onset muscle weakness that was greater
      distally than proximally, as well as respiratory insufficiency, cardiomyopathy,
      and cervical spine anomalies. Electromyography studies indicated myopathy and
      findings consistent with neuropathy in both. In the deltoid muscle of patient 1
      and the anterior tibial muscle of patient 2, myriad type 1 fibers harbored large,
      irregularly polygonal, and mostly central hyaline masses, small vacuoles, and
      nemaline rods flanking the hyaline masses or congregated under the sarcolemma.
      The hyaline masses are intensely congophilic; react strongly for desmin, alphaB
      crystallin, alpha1-antichymotrypsin, and ubiquitin and variably for gelsolin and
      dystrophin; and are devoid of alpha-actinin, nebulin, titin, and slow myosin. The
      presence of ubiquitin, gelsolin, and fragmented filaments, and the absence of
      nebulin, titin, alpha-actinin, and slow myosin in the hyaline masses, signal
      nonlysosomal protein degradation. Ultrastructurally, the hyaline masses are
      composed of intermediate-density amorphous material intermingled with fragmented
      filaments and irregularly branching, pleomorphic, highly electron-dense material,
      resembling the hyaline structures of myofibrillar myopathy. We conclude that the
      pathological process in this syndrome is one that induces destruction of
      myofibrillar components, resulting in aggregation of the degraded residues in
      hyaline masses, and causes replication of Z disks, resulting in formation of
      nemaline rods.

PMID- 11835380
TI  - Environmental enrichment slows disease progression in R6/2 Huntington's disease
      mice.
AB  - Huntington's disease is a genetic disorder that causes motor dysfunction,
      personality changes, dementia, and premature death. There is currently no
      effective therapy. Several transgenic models of Huntington's disease are
      available, the most widely used of which is the R6/2 mouse, because of its rapid
      disease progression. Environmental enrichment alters gene expression in the
      normal mouse brain, and modulates the course of several neurological disorders.
      Environmentally enriched mice may actually mimic human disease more accurately.
      We found that even limited environmental enrichment slows decline in RotaRod
      performance in R6/2 mice, despite rapid disease progression, whereas in normal
      littermates, maximal enrichment was required to induce a marked improvement in
      behavioral tests. Enrichment also delayed the loss of peristriatal cerebral
      volume in R6/2 brains. These results could provide the basis for a rational
      approach to ameliorate the effects of Huntington's disease.

PMID- 11835381
TI  - Abnormal SMN1 gene copy number is a susceptibility factor for amyotrophic lateral
      sclerosis.
AB  - The etiology of amyotrophic lateral sclerosis remains unknown in the majority of
      cases. Homozygous SMN1 (survival motor neuron) gene deletion causes spinal
      muscular atrophy, and SMN2 gene deletions are possible risk factors in lower
      motor neuron disease. We studied SMN1 and SMN2 genes copy numbers in 167
      amyotrophic lateral sclerosis patients and in 167 matched controls. We noted that
      16% of amyotrophic lateral sclerosis patients had an abnormal copy number of the
      SMN1 gene (1 or 3 copies), compared with 4% of controls. An abnormal SMN1 gene
      locus may be a susceptibility factor for amyotrophic lateral sclerosis.

PMID- 11835382
TI  - German Cancer Society Neuro-Oncology Working Group NOA-03 multicenter trial of
      single-agent high-dose methotrexate for primary central nervous system lymphoma.
AB  - The prospective multicenter NOA-03 trial, conducted by the Neuro-Oncology Working
      Group (NOA) of the German Cancer Society, was initiated to define the feasibility
      and efficacy of single-agent high-dose methotrexate therapy without concomitant
      radiotherapy in immunocompetent patients with primary central nervous system
      lymphoma. Thirty-seven patients (median age, 60 years) received 179 biweekly
      courses of 8 g/m2 methotrexate. Response was assessed after 3 and 6 courses. We
      had planned to enter 105 patients into the trial. Since fewer than the projected
      18 of 37 patients achieved a complete response after an intermediate analysis,
      the trial was closed. In intention-to-treat analysis, 11 of 37 patients (29.7%)
      achieved complete response, whereas 14 of 37 patients (37.8%) were found to have
      progressive disease. The median relapse-free survival among complete response
      patients was 13.7 months. Multivariate logistic regression analysis revealed that
      corticosteroid application during the first methotrexate course was associated
      with complete response. The regimen was well tolerated, but, unlike previously
      reported results, the activity of high-dose methotrexate was only moderate.

PMID- 11835383
TI  - Localization of autosomal recessive early-onset parkinsonism to chromosome 1p36
      (PARK7) in an independent dataset.
AB  - Two new loci, PARK6 and PARK7, for autosomal recessive early-onset parkinsonism
      have recently been identified on chromosome 1p, in single large pedigrees. Among
      4 autosomal recessive early-onset families analyzed here, 2 supported linkage to
      PARK7, 1 with conclusive evidence. These data confirm localization of autosomal
      recessive early-onset parkinsonism to PARK7, suggesting it to be a frequent
      locus. Assignment of families to either PARK6 or PARK7 might be difficult because
      of the proximity of the two loci on chromosome 1p.

PMID- 11835384
TI  - Childhood cerebellar hemangioblastoma does not predict germline or somatic
      mutations in the von Hippel-Lindau tumor suppressor gene.
AB  - Tumor suppressor gene "knockout" models would predict that children who present
      with hemangioblastoma are likely to harbor germline mutation of the von Hippel
      Lindau gene. We screened 6 pediatric patients with cerebellar hemangioblastoma
      for germline or somatic mutations of the von Hippel-Lindau gene. Two had prior
      clinical manifestations of von Hippel-Lindau disease and, as expected, had
      germline von Hippel-Lindau gene mutations. Four children with solitary
      hemangioblastoma did not have a detectable germline deletion, rearrangement, or
      point mutation in their von Hippel-Lindau gene, and tumor specimens in 3 of these
      4 showed no somatic von Hippel-Lindau allelic loss. Solitary cerebellar
      hemangioblastoma in children does not predict a germline or somatic mutation in
      the von Hippel-Lindau tumor suppressor gene. The tumorigenesis of
      hemangioblastoma in younger patients may differ from that in adults, and may
      involve a molecular process unrelated to the von Hippel-Lindau tumor suppressor
      pathway.

PMID- 11835385
TI  - A functional polymorphism in the prodynorphin gene promotor is associated with
      temporal lobe epilepsy.
AB  - The prodynorphin gene (PDYN) encoding the anticonvulsant peptide dynorphin is a
      strong candidate for a seizure suppressor gene and thus a possible modulator of
      susceptibility to temporal lobe epilepsy. We performed a case control association
      study in 155 patients with nonlesional temporal lobe epilepsy and 202 controls
      and found that PDYN promotor low-expression L-alleles confer an increased risk
      for temporal lobe epilepsy in patients with a family history for seizures.
      Irrespective of the familial background, L-homozygotes display a higher risk for
      secondarily generalized seizures and status epilepticus.

PMID- 11835386
TI  - Mutations in each of the five subunits of translation initiation factor eIF2B can
      cause leukoencephalopathy with vanishing white matter.
AB  - Leukoencephalopathy with vanishing white matter is a recently defined autosomal
      recessive disorder. The course is chronic progressive with additional episodes of
      rapid deterioration, provoked by fever and minor head trauma. A previous study
      showed that mutations in the genes encoding the epsilon- or the beta-subunit of
      the eukaryotic translation initiation factor eIF2B, a complex consisting of five
      subunits, cause the disease in most patients. Seven unsolved patients remained.
      The unsolved patients were investigated by mutation analysis of the genes
      encoding the alpha-, gamma-, and delta-subunit of eIF2B and the gene encoding the
      alpha-subunit of eIF2, because phosphorylation of this latter subunit regulates
      eIF2B activity. Mutations were found in the genes encoding the alpha- (1
      patient), gamma- (2 patients), and delta-subunits (2 patients) of eIF2B, but no
      mutations were found in the gene encoding the alpha-subunit of eIF2. In 2, both
      less typical patients, no mutations were found. Mutations in all five genes eIF2B
      subunit genes can cause VWM. eIF2B is essential for the initiation of translation
      of RNA into protein and is involved in regulation of the process, especially
      under circumstances of stress, such as fever. A defect in eIF2B may explain the
      sensitivity to stress factors in vanishing white matter patients.

PMID- 11835387
TI  - Polymerase chain reaction amplification of expanded ATTCT repeat in
      spinocerebellar ataxia type 10.

PMID- 11835388
TI  - Near-infrared spectroscopy in chronic progressive external ophthalmoplegia:
      adipose tissue thickness confounds decreased muscle oxygen consumption.

PMID- 11835389
TI  - Cranial nerve palsies: herpes simplex virus type 1 and varizella-zoster virus
      latency.

PMID- 11835391
TI  - Modulation of HeLa cells spreading by the non-receptor tyrosine kinase ACK-2.
AB  - The CDC42 regulated non-receptor tyrosine kinase ACK-2 has been associated with
      integrin signaling. In this report, the effect of ACK-2 on the modulation of cell
      spreading and motility was examined. HeLa cells expressing epitope-tagged wild
      type ACK-2 showed a slower rate of spreading on fibronectin when compared with
      untransfected cells. An ACK-2 protein lacking its SH3 domain was still capable of
      modulating HeLa cell spreading suggesting that its tyrosine kinase activity is
      sufficient to induce the observed phenotype. The ACK-2 effect on the rate of cell
      spreading did not involve inhibition of integrin-mediated activation of PI-3K
      signaling, since it did not alter membrane translocation of a GFP-PH-AKT domain
      (AKT pleckstrin homology domain) used as a reporter for PI-3K products induced by
      cell adhesion. The ACK-2 effect appears to be upstream from the adapter protein
      CrkII, since co-expression of CrkII and ACK-2 results in a neutralization of ACK
      2 mediated effects on HeLa cell spreading. Similarly, co-expression of p130Cas,
      which interacts with the adapter protein CrkII, with ACK-2, also results in a
      partial reversion of the ACK-2 effects on cell spreading. CrkII mediated reversal
      of the ACK-2 induced phenotype requires the activity of the small GTPase, Rap1.
      Co-expression of ACK-2 and CrkII with a dominant negative form of Rap1 reverses
      the neutralization by CrkII suggesting that CrkII mediated activation of Rap1 is
      required. However, an active form of Rap1 is not sufficient to reverse the ACK-2
      phenotype by itself. A role for Rac1 in ACK-2 effects was also established. An
      activated Rac1 protein neutralized the ACK-2 mediated inhibition of cell
      spreading. A direct measurement of cell motility by either a modified Boyden
      chamber or wounding assay demonstrates that ACK-2 overexpression increases the
      motility of the cells. These results suggest that ACK-2 modulates HeLa cells
      spreading upstream of pathways regulated by CrkII and that ACK-2 may regulate
      cell motility by controlling the activation of small GTPases such as Rap1 and
      Rac1.

PMID- 11835392
TI  - BRCA1 modulates ionizing radiation-induced nuclear focus formation by the
      replication protein A p34 subunit.
AB  - Mutations in BRCA1 account for a significant proportion of familial breast and
      ovarian cancers. BRCA1 has been implicated in DNA damage responses including
      double-strand break (DSB) repair. However, its exact role in DSB repair and its
      functional relationship with other known repair proteins remain to be elucidated.
      In this study, we carried out a cytological analysis of the effect of BRCA1 on
      damage-induced nuclear focus formation mediated by the replication protein A
      (RPA). RPA is a multi-functional protein that participates in both DNA
      replication and various types of DNA repair including DSB repair. Following
      ionizing radiation (IR), RPA and BRCA1 formed punctate nuclear staining patterns
      that co-localized with each other, consistent with the implicated roles of both
      proteins in the same repair process. The number of damage-induced RPA foci in
      BRCA1-deficient cells, however, was significantly greater than that in BRCA1
      positive cells. Moreover, the effect of BRCA1 on the RPA staining pattern
      appeared to be specific for IR but not ultraviolet (UV) irradiation. These data
      suggest that BRCA1 plays an important role in processing the RPA-associated
      intermediates during DSB repair.

PMID- 11835394
TI  - Arsenite stabilizes IkappaBalpha and prevents NF-kappaB activation in IL-1 beta
      stimulated Caco-2 cells independent of the heat shock response.
AB  - Recent studies suggest that sodium arsenite downregulates NF-kappaB activity by
      inhibiting phosphorylation and subsequent degradation of IkappaBalpha. Many
      effects of sodium arsenite are secondary to induction of heat shock proteins. The
      role of the heat shock response in arsenite-induced inhibition of NF-kappaB,
      however, is not known. We examined the involvement of the heat shock response in
      arsenite-induced inhibition of NF-kappaB activity in IL-1beta-stimulated Caco-2
      cells, a human colorectal adenocarcinoma cell line with enterocytic properties.
      Treatment of the cells with IL-1beta resulted in increased IkappaB kinase
      activity, reduced levels of IkappaBalpha and increased NF-kappaB DNA binding
      activity. Sodium arsenite blocked all of these responses to IL-1beta without
      inducing changes in heat shock factor activity or heat shock protein levels.
      Results from additional experiments showed that the protective effect of sodium
      arsenite on IkappaBalpha was not influenced by the oxygen radical scavenger
      catalase or by inhibitors of the MAP-kinase signaling pathway. The present
      results suggest that sodium arsenite stabilizes IkappaBalpha and prevents NF
      kappaB activation in IL-1beta-stimulated Caco-2 cells independent of the heat
      shock response. In addition, stabilization of IkappaBalpha by sodium arsenite
      does not require oxygen radical formation or activation of the MAP kinase
      signaling pathway.

PMID- 11835393
TI  - Association between alphavbeta6 integrin expression, elevated p42/44 kDa MAPK,
      and plasminogen-dependent matrix degradation in ovarian cancer.
AB  - Altered expression of alphav integrins plays a critical role in tumor growth,
      invasion, and metastasis. In this study, we show that normal human epithelial
      ovarian cell line, HOSE, and ovarian cancer cell lines, OVCA 429, OVCA 433, and
      OVHS-1, expressed alphav integrin and associated beta1, beta3, and beta5
      subunits, but only ovarian cancer cell lines OVCA 429 and OVCA 433 expressed
      alphavbeta6 integrin. The expression of alphavbeta6 in OVCA 429 and OVCA 433 was
      far higher than alphavbeta3 and alphavbeta5 integrin and correlated with high
      p42/p44 mitogen activated protein kinase (MAPK) activity and high secretion of
      high molecular weight urokinase plasminogen activator (HMW-uPA), pro
      metalloproteinase 2 and 9 (pro-MMP-9 and pro-MMP-2). In contrast to HOSE and OVHS
      1, OVCA 433 and OVCA 429 exhibited approximately 2-fold more plasminogen
      dependent [3H]-collagen type IV degradation. Plasminogen-dependent [3H]-collagen
      IV degradation was inhibited by inhibitor of uPA (amiloride) and MMP
      (phenanthroline) and by antibodies against uPA or MMP-9 or alphavbeta6 integrin,
      indicating the involvement of alphavbeta6 integrin, uPA and MMP-9 in the process.
      The alphavbeta6 correlated increase in HMW-uPA and pro-MMP secretion could be
      inhibited by tyrosine kinase inhibitor genistein or the MEK 1 inhibitor U0126,
      consistent with a role of active p42/44 MAPK in the elevation of uPA, MMP-9, and
      MMP-2 secretion. Under similar conditions, genistein and U0126 inhibited
      plasminogen-dependent [3H]-collagen type IV degradation. These data suggest that
      sustained elevation of p42/44 MAPK activity may be required for the co-expression
      of alphavbeta6 integrin, which in turn may regulate the malignant potential of
      ovarian cancer cells via proteolytic mechanisms.

PMID- 11835395
TI  - CDP and AP-2 mediated repression mechanism of the replication-dependent hamster
      histone H3.2 promoter.
AB  - The replication-dependent hamster histone H3.2 promoter contains two tandem CCAAT
      repeats located upstream of the TATA element. It has been shown that the NF-Y/CBF
      complex binds to a single CCAAT motif with high affinity, whereas the CCAAT
      displacement protein (CDP) binds to at least two CCAAT motifs in close proximity.
      Here, we report that the two CCAAT motifs within the H3.2 promoter confer
      transcriptional repression of the promoter during the cell cycle. While we cannot
      detect direct association of CDP with Rb in vitro, we discover that CDP can bind
      AP-2, a ubiquitous factor that interacts with Rb. The interaction domains between
      CDP and AP-2 are mapped to the highly conserved cut repeats of CDP as well as the
      basic and dimerization region of AP-2. Further, in transfection assays, CDP and
      AP-2 act synergistically to suppress the H3.2 promoter. Together, these data
      support a repression mechanism mediated by CDP and AP-2 that regulates H3.2 gene
      expression during the mammalian cell cycle.

PMID- 11835396
TI  - Insulin-like growth factor-1 protects peroxynitrite-induced cell death by
      preventing cytochrome c-induced caspase-3 activation.
AB  - We investigated the effect of IGF-1 on cell death induced by peroxynitrite in
      human neuroblastoma SH-SY5Y cells. Exposure of the cells to 3
      morpholinosydnonimine (SIN-1), a peroxynitrite donor, caused cytochrome c release
      from the mitochondria, caspase-3-like activation, and cell death. Pre-incubation
      of the cells with the caspase-3 inhibitor partially prevented SIN-1-induced cell
      death. Simultaneous addition of IGF-1 reduced SIN-1-induced caspase-3-like
      activation and cell death, whereas IGF-1 failed to reduce the release of
      cytochrome c. IGF-1 increased Akt phosphorylation, and Akt phosphorylation was
      inhibited by wortmannin, an inhibitor of phosphatidylinositol 3-kinase. In
      addition, wortmannin prevented IGF-1-evoked inhibition of cell death and caspase
      3-like activation. In a cell-free system, addition of cytochrome c to cytosolic
      fraction resulted in caspase-3-like activation. The activation was reduced when
      the cytosolic fraction prepared from IGF-1-treated cells was used. These results
      suggest that IGF-1 protects peroxynitrite-induced cell death downstream of
      cytochrome c release through the inhibition of caspase-3-like activation.

PMID- 11835397
TI  - Role of N-cadherin- and integrin-based costameres in the development of rat
      cardiomyocytes.
AB  - Costameres, vinculin-containing structures found in skeletal and cardiac muscle,
      are thought to anchor the Z-discs of the peripheral myofibrils to the sarcolemma.
      Several lines of evidence indicate that two different sets of costameres,
      integrin- and N-cadherin-based, are present in cardiac muscles. In this study,
      immunoblot analysis was used to study the expression of N-cadherin, alpha
      catenin, beta-catenin, vinculin, talin, and laminin in rat cardiac muscles at
      embryonic days 15 and 19, the day of birth (postnatal day 0), postnatal weeks 1,
      2, 3, and 4, and in the adult. Double immunofluorescence microscopy was performed
      to study the spatial and temporal distribution of these two sets of costameres in
      rat cardiomyocytes. Costameric staining for N-cadherin, codistributed with beta
      catenin, was strong from embryonic day 15 up to postnatal week 2, gradually
      decreased after postnatal week 3, and was undetectable at postnatal week 4 and in
      the adult. Confocal microscopy showed that N-cadherin colocalized with alpha
      actinin at cortical myofibrils. Double-labeling of beta-catenin and talin
      indicated the coexistence of N-cadherin/catenin- and integrin/talin-based
      costameres in rat cardiac muscle. Although beta-catenin and vinculin were co
      localized at the costamere of cardiomyocytes from embryonic day 15 to postnatal
      week 3, staining for beta-catenin or talin was mutually exclusive at all stages
      examined. These results demonstrate the simultaneous, but mutually exclusive,
      existence of N-cadherin/catenin- and integrin/talin-based costameres in rat
      cardiomyocytes between late embryonic stages and postnatal week 3, while only
      integrin/talin-based costameres were found in adult rats. The N-cadherin/catenin
      based costameres in rat cardiac muscles may play a role in myofibrillogenesis
      similar to that of their counterparts in cultured cardiomyocytes.

PMID- 11835398
TI  - Phytoestrogen genistein stimulates the production of osteoprotegerin by human
      trabecular osteoblasts.
AB  - The anti-resorptive effects of estrogen on bone metabolism are thought to be
      mediated through modulation of paracrine factors produced by osteoblastic lineage
      cells that act on osteoclastic lineage cells. Receptor activator of nuclear
      factor-kappaB ligand (RANKL) is the essential factor for osteoclast formation and
      activation and enhances bone resorption. By contrast, osteoprotegerin (OPG),
      which is produced by osteoblastic lineage cells acts as a decoy receptor that
      neutralizes RANKL and prevents bone loss. Recently, 17 beta-estradiol was found
      to stimulate OPG mRNA levels and protein secretion in a human osteoblastic cell
      line through activation of the estrogen receptor (ER)-alpha. In this study, we
      assessed the effects of the phytoestrogen genistein on OPG mRNA steady state
      levels (by semiquantitative RT-PCR and Northern analysis) and protein production
      (by ELISA) in primary human trabecular osteoblasts (hOB) obtained from healthy
      donors. Genistein increased OPG mRNA levels and protein secretion by hOB cells by
      up to two- to six-fold in a dose- (P<0.0001) and time-dependent (P<0.0001)
      fashion with a maximum effect at 10(-7) M. Co-treatment with the pure ER
      antagonist ICI 182,780 completely abrogated the stimulatory effects of genistein
      on OPG protein secretion, indicating that these effects were specific and
      directly mediated through the ER. Pre-treatment with genistein partially
      prevented the inhibitory effects of the glucocorticoid dexamethasone on OPG mRNA
      and protein production. The stimulation of OPG mRNA levels by genistein was not
      affected by the protein synthesis inhibitor, cycloheximide and was shown to be
      due to enhancement of OPG gene transcription. In conclusion, our data suggest
      that the phytoestrogen genistein is capable of upregulating the production of OPG
      by human osteoblasts. Thus, dietary sources of phytoestrogens may help to prevent
      bone resorption and bone loss by enhanced osteoblastic production of OPG.

PMID- 11835399
TI  - Functional receptor for platelet-derived growth factor in rat embryonic heart
      derived myocytes: role of sequestered Ca2+ stores in receptor signaling and
      antagonism by arginine vasopressin.
AB  - Platelet-derived growth factor (PDGF) is established to function importantly in
      the growth, development, and function of most cardiovascular tissues. However,
      evidence that the factor participates directly in the growth and development of
      the mammalian myocardium is lacking. H9c2 rat embryonic ventricular myocytes were
      found to respond to PDGF-BB with a rapid mobilization of cell-associated Ca2+ and
      increased rates of protein synthesis, followed by markedly increased rates of DNA
      synthesis. PDGF acted as a full mitogen for these myocytes. Evidence is provided
      that documents the expression of classical PDGF-beta, but not PDGF-alpha,
      receptors in H9c2 cells. Scatchard analysis revealed the presence of 44,000 beta
      receptors per myocyte. Cell shortening and clustering of plasmalemmal beta
      receptors occurred within 30 min of exposure to PDGF-BB. Treatment was also
      associated with a transient increase in the rate of synthesis of GRP78/BiP,
      consistent with a transitory release of Ca2+ from the sarcoplasmic/endoplasmic
      reticulum [S(E)R]. Increased rates of protein synthesis at early times of PDGF
      treatment were additive with those occurring in response to arginine vasopressin,
      indicating different mechanisms of translational upregulation by these agents.
      The mitogenic effects of PDGF were delayed by vasopressin, which causes H9c2
      myocytes to undergo hypertrophy while promoting the persistent depletion of S(E)R
      Ca2+ stores. In the presence of PDGF, vasopressin did not induce hypertrophy. As
      compared to untreated myocytes, DNA synthesis in PDGF-treated myocytes was
      optimized at lower extracellular Ca2+ concentrations and was significantly less
      sensitive to inhibition by ionomycin. H9c2 cells appear to provide a useful
      embryonic cardiomyocyte model in which to examine both PDGF-activated
      proliferative and vasopressin-activated hypertrophic events and the importance of
      transient vs. sustained Ca2+ release in these events.

PMID- 11835400
TI  - Arsenite stimulates cyclooxygenase-2 expression through activating IkappaB kinase
      and nuclear factor kappaB in primary and ECV304 endothelial cells.
AB  - Epidemiological studies have shown that chronic exposure to arsenic can result in
      liver injury, peripheral neuropathy, arteriosclerosis, and an increased incidence
      of cancer of the lung, skin, bladder, and liver. The overexpression of inducible
      cyclooxygenase-2 (Cox-2) has been associated with vascular inflammation and
      cellular proliferation. However, the effect of arsenite on Cox-2 gene expression
      in endothelial cells was left to be investigated. Western Blot analysis of HUVECs
      revealed a two-fold induction of Cox-2 protein by arsenite. This induction was
      associated with a two-fold increase of prostaglandin E2 in the media.
      Furthermore, the level of Cox-2 mRNA was correspondingly elevated as demonstrated
      by both Northern blot and reverse transcriptase-polymerase chain reaction (RT
      PCR) analyses. Transfection of an immortalized human endothelium cell line
      (ECV304) with Cox-2 reporter gene constructs demonstrated that the transcription
      of Cox-2 gene was enhanced by arsenite. This induction was attenuated by
      pyrrolidine dithiocarbamate (PDTC), an inhibitor of NFkappaB. In addition,
      electrophoretic mobility shift assays indicated that NFkappaB activity was
      induced by arsenite. The kinase activity assay also indicated that IkappaB kinase
      (IKK) activity was induced by arsenite. These findings indicated that the
      induction of Cox-2 gene transcription by arsenite was through the stimulation of
      NFkappaB activity. Arsenite could induce IKK activity, which leads to the
      phosphorylation and degradation of IkappaB in ECV304 cells. Therefore, it appears
      that IKK signaling pathway is involved in arsenite-mediated Cox-2 expression.

PMID- 11835401
TI  - Inhibition of PDGF-stimulated and matrix-mediated proliferation of human vascular
      smooth muscle cells by SPARC is independent of changes in cell shape or cyclin
      dependent kinase inhibitors.
AB  - Interactions among growth factors, cells, and extracellular matrix regulate
      proliferation during normal development and in pathologies such as
      atherosclerosis. SPARC (secreted protein, acidic, and rich in cysteine) is a
      matrix-associated glycoprotein that modulates the adhesion and proliferation of
      vascular cells. In this study, we demonstrate that SPARC inhibits human arterial
      smooth muscle cell proliferation stimulated by platelet-derived growth factor or
      by adhesion to monomeric type I collagen. Binding studies with SPARC and SPARC
      peptides indicate specific and saturable interaction with smooth muscle cells
      that involves the C-terminal Ca2+-binding region of the protein. We also report
      that SPARC arrests monomeric collagen-supported smooth muscle cell proliferation
      in the late G1-phase of the cell cycle in the absence of an effect on cell shape
      or on levels of cyclin-dependent kinase inhibitors. Cyclin-dependent kinase-2
      activity, p107 and cyclin A levels, and retinoblastoma protein phosphorylation
      are markedly reduced in response to the addition of exogenous SPARC and/or
      peptides derived from specific domains of SPARC. Thus, SPARC, previously
      characterized as an inhibitor of platelet-derived growth factor binding to its
      receptor, also antagonizes smooth muscle cell proliferation mediated by monomeric
      collagen at the level of cyclin-dependent kinase-2 activity.

PMID- 11835402
TI  - PU.1 regulates the expression of the vav proto-oncogene.
AB  - Vav is a guanine nucleotide exchange factor for the rho/rac GTPases that is
      upregulated in the embryo during the transition from primitive to definitive
      hematopoiesis. It is one of several genetic markers that correlates with the
      differentiation of the intraembryonic definitive hematopoietic stem cell.
      Subsequently, in the adult, vav is expressed predominantly in cells of the
      hematopoietic system. A heat-resistant protein complex that bound to a 23-bp
      segment, which is essential for vav promoter activity, was found to be present in
      myeloid cells but not T-cells. The complex was absent in non-hematopoietic cells
      which normally do not express vav. Using a saturation mutagenesis method, Mutex,
      a "footprint" of the protein binding site (AGAGGAAGT) was obtained that was
      consistent with the consensus binding site for PU.1. A specific antibody to PU.1
      supershifted the complex and identified the presence of PU.1 within the complex.
      A GST fusion protein of the human PU.1 bound to the same consensus sequence as
      the heat-resistant complex from myeloid lineages. Specific mutation of the GGAA
      PU.1 core binding site silenced vav promoter activity and a dominant negative
      PU.1 inhibited the transactivation of PU.1 at the vav promoter as measured by the
      expression of the EGFP reporter gene. In addition, PCR analysis of
      immunoprecipitated chromatin using specific antibodies for PU.1 detected the co
      immunoprecipitation of DNA containing the vav promoter. These results suggest
      that PU.1 is essential for transcriptional activity of the vav promoter in
      myeloid cells.

PMID- 11835403
TI  - Signalling pathways involved in the direct effects of IGFBP-5 on breast
      epithelial cell attachment and survival.
AB  - We have demonstrated previously that IGFBP-5 can confer survival against
      apoptosis induced by ceramide, C2, or a small synthetic arginine-glycine-aspartic
      acid (RGD)-containing peptide in a direct manner. The endogenous ceramide-induced
      pathway is normally counter-balanced by survival signals mediated by sphingosine
      kinase (SK) and protein kinase C (PKC). In order to investigate whether these
      pathways are involved in the IGFBP-5 survival effect, we have used inhibitors of
      SK (N, N-di-methyl sphingosine, DMS) and PKC (chelerythrine chloride, CC). The
      effect of pre-incubating Hs578T breast cancer cells with IGFBP-5 on cell adhesion
      or on subsequent cell death induced by C2 or RGD was investigated with and
      without the presence of DMS or CC. Cell death was determined by trypan blue cell
      counts and apoptosis confirmed by morphological assessment and flow cytometry.
      Cell attachment was determined by a cell adhesion assay. The presence of IGFBP-5
      significantly inhibited cell death induced by C2 or RGD, compared to the triggers
      of apoptosis alone (P<0.01 in both cases). In the presence of either IGFBP-5, CC
      or DMS, there was no significant effect on cell death compared to the control.
      IGFBP-5 in the presence of either inhibitor resulted in a significant increase in
      cell death; IGFBP-5 also lost its ability to confer survival on C2 and RGD
      induced apoptosis and in contrast significantly increased cell death. In the cell
      adhesion assay, IGFBP-5 significantly increased cell attachment over basal
      levels. In the presence of either inhibitor the IGFBP-5 effect on cell adhesion
      was reversed and cell attachment was reduced to below basal levels. These data
      suggest that IGFBP-5 promotes the attachment and survival of Hs578T cells by
      modulating the balance between ceramide and opposing survival signals.

PMID- 11835404
TI  - Identification of transcription factor in the promoter region of rat regucalcin
      gene: binding of nuclear factor I-A1 to TTGGC motif.
AB  - Hepatic nuclear protein has been reported to bind specifically to the TTGGC
      sequence of the rat regucalcin gene promoter region in stimulating the promoter
      activity (Misawa and Yamaguchi [2000] Biochem. Biophys. Res. Commun. 279: 275
      281). The present study was undertaken to identify transcription factor, which
      binds to TTGGC motif in the rat regucalcin gene promoter, using the yeast one
      hybrid system. The sequence between -525 and -504, which has been defined as a
      functional promoter element II-b, was used as bait to screen a rat liver cDNA
      library. Two cDNA clones were identified as a nuclear factor I-A1 (NF1-A1). The
      results of gel mobility shift assay and mutation analysis using recombinant NF1
      A1 protein showed that this protein could specifically bind to TTGGC motif of the
      II-b oligonucleotide in promoter region. The expression of NF1-A1 mRNA was found
      in the liver, kidney, heart, spleen, and brain of rats. This study demonstrates
      that NF1-A1 is a transcription factor in stimulating the rat regucalcin gene
      promoter activity.

PMID- 11835405
TI  - Lack of requirement of STAT1 for activation of nuclear factor-kappaB, c-Jun NH2
      terminal protein kinase, and apoptosis by tumor necrosis factor-alpha.
AB  - Tumor necrosis factor (TNF) is one of the most potent activators of nuclear
      transcription factor NF-kappaB, c-Jun N-terminal protein kinase (JNK), and
      apoptosis in a wide variety of cells. The biological effects of TNF are mediated
      through sequential interactions of various cytoplasmic proteins with
      intracellular domains of TNF receptors. Whether signal transducer and activator
      of transcription-1 (STAT1), which mediates interferon (IFN) signaling, also plays
      any role in the TNF-mediated activation of NF-kappaB, JNK, and apoptosis has not
      been established. Here, we report our investigation of the role of STAT1 in TNF
      signaling using STAT1-deficient U3A and STAT1-stably transfected U3A-PSG91 cells.
      IFNalpha inhibited the proliferation of STAT1-expressing U3A-PSG91 cells but had
      no effect on STAT1-negative U3A cells. TNF alone, even up to 10 nM, had no effect
      on the proliferation of either U3A-PSG91 or U3A cells. Irrespective of STAT1
      status, TNF induced cytotoxic effects in the presence of cycloheximide (CHX) in
      both cell types. Additionally, TNF-induced caspase-3 and caspase-8 activation and
      TNF-induced PARP cleavage were unaffected by the presence or absence of STAT1.
      TNF activated NF-kappaB, consisting of p50 and p65, in both U3A and U3A-pSG91
      cells in a dose- and time-dependent manner, but the degree and rate of activation
      were slightly lower in U3A cells, as were IkappaBalpha degradation and NF-kappaB
      dependent reporter gene expression. STAT1 was, however, required for IFNalpha
      mediated downregulation of TNF-induced NF-kappaB activation. TNF activated JNK in
      both cell types, but dose and time of exposure required for optimum activation
      differed slightly. Thus, overall our results indicate that STAT1 plays a minimal
      role in TNF-mediated cellular responses.

PMID- 11835406
TI  - Wnt signaling during BMP-2 stimulation of mesenchymal chondrogenesis.
AB  - Members of both the Wnt and bone morphogenetic protein (BMP) families of
      signaling molecules have been implicated in the regulation of cartilage
      development. A key component of the Wnt signaling pathway is the cytosolic
      protein, beta-catenin. We have recently shown that the chondrogenic activity of
      BMP-2 in vitro involves the action of the cell-cell adhesion protein, N-cadherin,
      which functionally complexes with beta-catenin. The aim of this study is to test
      the hypothesis that Wnts may be involved in BMP-2 induced chondrogenesis, using
      an in vitro model of high-density micromass cultures of the murine multipotent
      mesenchymal cell line, C3H10T1/2. Expression of a number of Wnt members was
      detected in these cultures, including Wnt-3A and Wnt-7A, whose levels were up-
      and downregulated, respectively, by BMP-2. To assess the functional involvement
      of Wnt signaling in BMP-2 induced chondrogenesis, cultures were treated with
      lithium chloride, a Wnt-7A mimetic that acts by inhibiting the serine/threonine
      phosphorylation activity of glycogen synthase kinase-3beta (GSK-3beta). Lithium
      treatment significantly inhibited BMP-2 stimulation of chondrogenesis as well as
      GSK-3beta enzymatic activity, and decreased the levels of N-cadherin protein and
      mRNA. Furthermore, lithium decreased BMP-2 upregulation of total and nuclear
      levels of LEF-1 and beta-catenin as well as their interaction during later
      chondrogenesis; similarly, the interaction of beta-catenin with N-cadherin was
      also decreased. Interestingly, lithium treatment did not affect the ability of
      BMP-2 to decrease ubiquitination of beta-catenin, although it did reduce the
      interaction of beta-catenin with GSK-3beta during late chondrogenesis (days 9
      13). We suggest that the chondro-inhibitory effect of lithium on BMP-2 induced
      chondrogenesis indicates antagonism between lithium-like Wnts and BMP-2 during
      mesenchymal condensation.

PMID- 11835407
TI  - Differences in the nuclear chromatin among various stages of the life cycle of
      Trypanosoma cruzi.
AB  - Trypanosoma cruzi is the etiological agent of Chagas. Although the nuclear
      chromatin of this parasite is organized in the form of nucleosome filaments, its
      chromatin is physically and enzymatically fragile, and no condensation into
      chromosomes occurs during mitosis. All previous investigations have been carried
      out with epimastigote form in its proliferate stage. It is not known whether
      these differences in chromatin structure are also found in the non-proliferate
      stationary epimastigote forms and in tissue derived trypomastigotes. Our results
      confirm that chromatin of logarithmic epimastigotes presents limited compaction
      when increasing salt concentrations from 1 to 100 mM NaCl, and no 30-nm fibers
      were formed. Contrary to these results, non-proliferative forms of the parasites
      showed a pattern of compactation similar to that observed in rat liver chromatin,
      where solenoids of 30-nm fibers are formed at 100-mM NaCl. In accordance with
      these results, digestion of the nuclear chromatin with DNase I revealed that the
      chromatin of logarithmic phase epimastigotes was more accessible to the enzyme.
      We conclude from these results that structural differences in the chromatin exist
      not only between T. cruzi and higher eukaryotes but also among various forms of
      the parasite. The functional significance of these differences are currently
      under investigation.

PMID- 11835408
TI  - Substrate specificity of protein tyrosine phosphatase: differential behavior of
      SHP-1 and SHP-2 towards signal regulation protein SIRPalpha1.
AB  - The substrate specificity of catalytic domains and the activation of full length
      protein tyrosine phosphatases, SHP-1 and SHP-2 have been investigated using
      synthetic phosphotyrosyl peptides derived from SIPRalpha1. We found that the
      catalytic domains of SHP-1 and SHP-2 exhibit different substrate specificity
      towards a longer trideca-peptide pY(469+3) ((-7)RPEDTLTpYADLDM(+5)) and not to
      the shorter decapeptide pY(469) ((-5)EDTLTpYADLD(+4)), the former being the
      substrate of SHP-2 only. Furthermore, the activation of full-length SHP-1 and not
      the SHP-2 by the deca/trideca-peptides suggested SIRPalpha 1 to be possibly
      acting as both an upstream activator and a substrate for SHP-1, and merely as the
      downstream substrate for SHP-2 in signaling events.

PMID- 11835411
TI  - Collection efficiencies of MNC subpopulations during autologous CD34+ peripheral
      blood progenitor cell (PBPC) harvests in small children and adolescents.
AB  - There is increasing demand for mononuclear cell (MNC) harvests not only for PBPC
      but also for immune therapies using dendritic cells and donor lymphocytes. We
      determined the collection efficiencies (CE) of various MNC subpopulations during
      CD34+ cell harvests using a Fenwal CS 3000 Plus Omnix system in small children
      and adolescents. The cell content of 140 leukapheresis products (LP) was
      prospectively evaluated in 45 pretreated patients with solid tumors and
      hematological malignancies. The median age was 12 years (range 0.8-22), and the
      median body weight (BW) 43 kg (range 9-92). Depending upon the BW of the
      patients, the media used for priming were saline (SP) in 86, human albumin (HA,
      HAP) in 10, and packed red blood cells (BP) in 44 apheresis procedures. The major
      nucleated cell (NC) fractions collected were monocytes (52% of NC) and CD3+ T
      cells (26%). The median cell yield for monocytes was 174 * 10(6)/kg (range 24
      613) representing a CE of 55%. The median number of CD3(+) T cells was 84 *
      10(6)/kg (range 5.6-380; CE = 74%). CD34+ cells represented a very small cell
      fraction of the LP (1.3% of NC), with a median yield of 4.2 * 10(6)/kg (range 0.2
      87) and a CE of 63%. The cell yield of various MNCs was significantly correlated
      with the cell count in the peripheral blood (PB) and with the blood volume
      processed (ANOVA, P < 0.0001). No influence on the CE was observed for the
      priming procedure, the patients' age or sex, or the other adaptations used in the
      harvesting protocol. In conclusion, the Fenwal CS 3000 Plus OMNIX system with the
      CD34+ cell program and the described adaptations, is also predictably useful for
      harvest of monocytes or lymphocytes in pediatric patients. We present regression
      equations that predict the cell yield of various MNC subpopulations in apheresis
      products.

PMID- 11835413
TI  - Apheresis treatment of recurrent focal segmental glomerulosclerosis after kidney
      transplantation: re-analysis of published case-reports and case-series.
AB  - A systematic re-analysis of published cases was performed to better define the
      role of plasmapheresis in the treatment recurrent focal segmental
      glomerulosclerosis after renal transplantation. Forty-four cases were identified,
      of which 32 responded to apheresis. The median number of treatments to response
      was 9. There was no difference between responders and nonresponders in the total
      number of treatments performed. The presence of sclerosis on biopsy predicted
      treatment failure. Relapse after first successful treatment was reported in 10
      cases. The median number of treatments received was less and the time from
      diagnosis to first treatment was greater for patients who relapsed than for
      patients in whom relapse was not reported, but the differences were not
      statistically significant. On the basis of this analysis, we recommend early
      treatment after diagnosis with a regimen of three daily plasmapheresis treatments
      followed by 6 treatments on an every other day basis.

PMID- 11835412
TI  - Questionable efficacy of plasma exchange for thrombotic thrombocytopenic purpura
      after bone marrow transplantation.
AB  - Thrombotic thrombocytopenic purpura (TTP) after bone marrow transplantation (BMT)
      is an uncommon complication presumably associated with extensive endothelial cell
      damage due to Cyclosporine, total body irradiation, or other drugs. While the
      majority of patients with primary TTP, which is considered to be an autoimmune
      process, respond to plasma exchange, TTP after BMT has a very poor prognosis. A
      total of 7 patients out of 307 patients who underwent BMT were diagnosed with TTP
      during 1989-1999. The diagnosis of TTP was made based on thrombocytopenia and
      microhemangiopathic hemolytic anemia characterized by an elevated LDH and the
      presence of schistocytes on the peripheral blood smear. Five patients were
      treated with plasma exchange (PE) using fresh frozen plasma and/or
      cryoprecipitate poor plasma as replacement fluid. One patient was treated using a
      protein A column. One patient did not receive plasma exchange because the 125
      patient was clinically stable and was discharged. It was hard to assess the
      efficacy of PE due to the multiplicity of the patients' clinical condition and
      laboratory data. At least 4 patients did not respond to PE and 2 patients were
      not able to be evaluated due to multi organ failure. However, all patients died.
      It is not clear at this moment if PE for patients with TTP after BMT is truly
      beneficial.

PMID- 11835414
TI  - Four patients with both thrombotic thrombocytopenic purpura and autoimmune
      thrombocytopenic purpura: the concept of a mixed immune thrombocytopenia syndrome
      and indications for plasma exchange.
AB  - Autoimmune thrombocytopenic purpura (ATP) and thrombotic thrombocytopenic purpura
      (TTP) are each well recognized clinical syndromes which may appear as single
      episodes or may have chronic relapsing courses. We present four patients negative
      for human immunodeficiency virus (HIV) infection who appear to have both
      diagnoses with either concomitant or intermingled episodes, and we review seven
      additional patients reported in the literature with similar features. All four of
      our patients are female, two have underlying connective tissue disorders, and
      their ATP processes came to our attention because of incomplete response of the
      platelet count to plasma exchange therapy (PEX) during a TTP phase (Cases 1 and
      2) or development of thrombocytopenia in the absence of microangiopathy on the
      background of prior typical TTP episodes (Cases 3 and 4). Recognition of the ATP
      diagnosis in each case resulted in discontinuation of PEX (Cases 1 and 2) or not
      instituting PEX (Cases 3 and 4). In each instance, a satisfactory rise in
      platelet count followed treatment for ATP. Based upon this experience, we
      conclude that some individuals may have a mixed immune thrombocytopenia syndrome;
      careful analysis of the mechanism of thrombocytopenia, especially in recurrent
      episodes and in patients who respond incompletely to PEX for TTP, is important
      when deciding whether to initiate or continue PEX, or to consider therapies
      appropriate for other mechanisms of thrombocytopenia.

PMID- 11835415
TI  - A new continuous-flow cell separation method based on cell density: principle,
      apparatus, and preliminary application to separation of human buffy coat.
AB  - With the recent progress in transfusion medicine, separation and isolation of
      cells in a large quantity is becoming increasingly important. At present, the
      continuous cell separation method in a preparative scale is limited to apheresis
      and elutriation: the former is mainly used for collection of platelet and buffy
      coat from the whole blood, while the latter separates cells virtually according
      to their size. Here we introduce a continuous flow method that separates cells
      entirely based on cell density. The method is gentle and capable of processing a
      large number of cells. The potential capability of the method was demonstrated on
      separation of lymphocytes and granulocytes from human buffy coat. Lymphocytes
      were enriched to 90% in the fraction at density = 1.065 and granulocytes are
      isolated in fractions at density = 1.075-1.080 while red cells were completely
      retained at the periphery of the channel. CD34 cells were distributed around
      1.065 and coeluted with lymphocytes, suggesting that further enrichment requires
      focusing the density gradient around 1.070. The method could process 10(9)
      nucleated cells in 2 hours. Our preliminary results suggest that the present
      method is an effective and efficient means to separate blood cells.

PMID- 11835417
TI  - Evaluation of women with clinically suspected thrombotic thrombocytopenic purpura
      hemolytic uremic syndrome during pregnancy.
AB  - Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS) is more
      common in women, and commonly occurs during pregnancy and the immediate
      postpartum period. An important clinical issue is the distinction of TTP-HUS from
      the more common obstetric complications, preeclampsia and HELLP syndrome
      (hemolysis, elevated liver function tests, low platelets). Clinical suspicion of
      TTP-HUS requires urgent intervention with plasma exchange treatment, a procedure
      with substantial risk, while preeclampsia and HELLP syndrome typically resolve
      spontaneously following delivery. Since clinical features of these syndromes can
      be similar, especially if preeclampsia becomes severe or if seizures (defining
      eclampsia) occur, the differential diagnosis may be arbitrary. This review
      addresses the evaluation and management of these syndromes and describes a
      clinical approach for determining when plasma exchange is appropriate.

PMID- 11835416
TI  - Bacterial contamination of blood products: factors, options, and insights.
AB  - Transfusion of bacterially contaminated blood products remains an overlooked
      problem. However, the risk of receiving a bacterially contaminated unit is
      greater than the combined risk of HIV-1/2, HCV, HBV, and HTLV I/II [American
      Association of Blood Banks Bulletin, no. 294, 1996]. Topics covered in this
      article include: the current incidence, clinical presentation and outcome,
      effective methods of detection, and ways to reduce bacterial contamination of
      blood products. There is no one existing strategy that can completely eliminate
      the risk of bacterial contamination. It is inevitable that partial solutions or
      combinations of methods will be implemented in the near future.

PMID- 11835418
TI  - Hypocalcemic toxicity and atypical reactions in therapeutic plasma exchange.
AB  - Hypocalcemic toxicity accounts for the most common adverse effects of therapeutic
      plasma exchange. The symptoms can be related to a fall in plasma ionized calcium.
      Citrate-based anticoagulants, notably sodium citrate and ACD formula A, have been
      indicated as the major cause of hypocalcemic toxicity, but colloid replacement
      fluids containing human serum albumin are also at fault. Recognition of the signs
      and symptoms of hypocalcemic toxicity is important because several clinical
      measures are available to deal with them and to ensure patient comfort. A typical
      reactions, characterized by flushing and hypotension during plasma exchange, have
      been attributed to the effects of angiotensin converting enzyme inhibitors. Both
      exchange and adsorption apheresis procedures can result in atypical reactions in
      patients who have been taking this class of drugs within 48 to 72 hours of an
      apheresis procedure. These reactions are less common than hypocalcemic toxicity,
      but can be prevented by paying attention to detail.

PMID- 11835420
TI  - The risk of lower urinary tract symptoms five years after the first delivery.
AB  - AIM OF THE STUDY: To estimate the prevalence and 5-year incidence of lower
      urinary tract symptoms (LUTS) after the first delivery and to evaluate the impact
      of pregnancy per se and delivery per se on long-lasting symptoms. MATERIALS AND
      METHODS: A longitudinal cohort study of 305 primiparae questioned a few days, 3
      months, and 5 years after their delivery. The questionnaire used was tested and
      validated, and the questions were formulated according to the definitions of the
      International Continence Society (ICS). Maternal, obstetric, and neonatal data
      concerning every delivery and objective data concerning surgeries during the
      observation period were obtained from the records. From the sample of 278 women
      (91%) who responded 5 years after their first delivery, three subpopulations were
      defined: 1) women without initial LUTS before or during the first pregnancy or
      during the puerperal period, 2) women with onset of LUTS during the first
      pregnancy, and 3) women with onset of LUTS during the first puerperium. The risk
      of LUTS 5 years after the first delivery was examined using bivariate analyses.
      The obstetric variables in the bivariate tests with a significant association
      with long-lasting urinary incontinence were entered into a multivariate logistic
      regression. RESULTS: The prevalence of stress and urge incontinence 5 years after
      first delivery was 30% and 15%, respectively, whereas the 5-year incidence was
      19% and 11%, respectively. The prevalence of urgency, diurnal frequency, and
      nocturia 5 years after the first delivery was 18%, 24%, and 2%, respectively,
      whereas the 5-year incidence was 15%, 20%, and 0.5%, respectively. The prevalence
      of all LUTS except nocturia increased significantly during the 5 years of
      observation. The risk of long-lasting stress and urge incontinence was related to
      the onset and duration of the symptom after the first pregnancy and delivery in a
      dose-response-like manner. Vacuum extraction at the first delivery was used
      significantly more often in the group of women with onset of stress incontinence
      during the first puerperium, whereas an episiotomy at the first delivery was
      performed significantly more often in the group of women with onset of stress
      incontinence in the 5 years of observation. The prevalence of urgency and diurnal
      frequency 5 years after the first delivery was not increased in women with
      symptom onset during the first pregnancy or puerperium compared with those
      without such symptoms. The frequency of nocturia 5 years after the first delivery
      was too low for statistical analysis. CONCLUSION: The first pregnancy and
      delivery may result in stress and urge incontinence 5 years later. Women with
      stress and urge incontinence 3 months after the first delivery have a very high
      risk of long-lasting symptoms. An episiotomy or a vacuum extraction at the first
      delivery seems to increase the risk. Subsequent childbearing or surgery seems
      without significant contribution. Long-lasting urgency, diurnal frequency, or
      nocturia cannot be predicted from onset during the first pregnancy or puerperium.

PMID- 11835421
TI  - Urinary incontinence symptom scores and urodynamic diagnoses.
AB  - The aim of this study was to determine whether scores on two validated urinary
      incontinence symptom scales predicted eventual urodynamic diagnoses. Two hundred
      ninety-three patients undergoing multi-channel urodynamic testing rated their
      symptoms of urinary incontinence and/or pelvic organ prolapse (POP), using the
      Incontinence Impact Questionnaire, the Urogenital Distress Inventory, and an
      obstructive symptom subscale from the long form of the Incontinence Impact
      Questionnaire. Among the 202 (69%) patients without advance-stage POP, increasing
      scores on scale items related to stress and urge incontinence predicted
      increasing frequency of the diagnoses of genuine stress incontinence (GSI) and
      detrusor instability, respectively. Among the 91 (31%) patients with advance
      stage POP, there was no association. Among all patients with GSI, the presence of
      intrinsic sphincter deficiency could not be predicted by responses to the symptom
      scales. Scores on the symptom scales were inadequate predictors of eventual
      urodynamic diagnoses, especially among women with advance-stage POP.

PMID- 11835422
TI  - Bother arising from urinary frequency in women.
AB  - Patients commonly express bother with the symptom of frequent urination. The
      relationship between actual voiding frequency and this symptom is undocumented.
      We reviewed records of 200 women who had completed 24-hour frequency-volume
      charts, and had indicated their degree of bother with urinary frequency utilizing
      the short form of the Urogenital Distress Inventory. The degree of bother was
      correlated with daytime and nighttime voiding frequency, maximum functional
      capacity, mean voided volume, and demographic variables. Among 200 women, 180
      (90%) indicated at least a minor degree of bother with urinary frequency. A
      voiding frequency of eight or more times in 24 hours was reported by 166 (83%) of
      women. Among the 34 women voiding fewer than eight times/24 hours, 26 (76%)
      reported bother with urinary frequency. There was large variation in the degree
      of bother reported at a given voiding frequency. Postmenopausal women without
      hormone replacement therapy (HRT) recorded more nighttime voids than those on
      HRT. Among postmenopausal women without HRT, mean voided volume and maximum
      functional capacity were inversely related to patient age. Our study suggests
      that the currently utilized cutoff value of eight daily voids to define urinary
      frequency, may not be helpful in the management of women in this country. A
      racially diverse study of the voiding habits of asymptomatic North American women
      is mandated.

PMID- 11835423
TI  - Reliability of pelvic floor muscle strength measurement in elderly incontinent
      women.
AB  - Pelvic floor muscles (PFM) play an important role in maintaining urinary
      continence with increasing age. Therefore, their contractile properties need to
      be evaluated. The aim of the study was to examine the reliability and correlation
      of simple techniques to measure PFM strength in elderly women with urinary
      incontinence. An interview was used to evaluate the ability to stop the urinary
      stream during micturition and to calculate the incontinence index. A pad test was
      applied to objectively evaluate the severity of the disease. Functional testing
      included a digital examination to measure the force and duration of one
      contraction, a perineometer measurement (Peritron) to assess maximal contraction
      force and contraction force of 5 s, and a cone-retention test (Femcon) while
      walking for 1 min and during Valsalva's manoeuvre. This procedure was performed
      on three separate occasions within one week. The 37 participating women with a
      mean age of 62+/-8 (mean+/-SD) years had a severity index of 4.4+/-2.6 and a
      urine loss of 9.5+/-13.6 mg during the pad test. Sixteen women were able to
      completely stop the urinary stream during micturition. The digital examination
      showed no intratester variability. The perineometer measurement showed that the
      absolute difference in maximal contraction force and mean contraction force
      within 5 s was less than 5.3 mm Hg and 4.5 mm Hg, respectively, with a
      probability of 0.95. While walking and during Valsalva's manoeuvre, 19 and 20
      women, respectively, held the same cone in place on all three occasions. The
      maximal contraction force and mean force during the 5-s contraction correlated
      well with the ability to stop the urinary stream and the digital examination but
      only weakly with the cone-retention tests. The reliability of PFM strength
      measurement is highest in the digital examination, followed by perineometer
      measurements, and then by vaginal cone tests. As PFM function is easy to assess,
      it should be routinely done in the assessment of urinary incontinence in elderly
      women.

PMID- 11835424
TI  - Development of a low-cost flow meter to grade the maximum flow rate.
AB  - We developed an inexpensive flow meter to grade the maximum flow rate of
      individuals at locations other than the clinical setting. This flow meter
      consists of a funnel connected to a collecting tube with several exit ports.
      Urine directed into this tube flows through one or more ports and is collected in
      a measuring cup to measure the voided volume. The number of ports emitting the
      liquid is a measure for the flow rate. We made four experimental models to test
      and compare some of the physical properties. One of these models was selected as
      a prototype and was tested in five healthy volunteers. All volunteers voided
      repeatedly in a standard rotating disk flow meter and in this prototype to test
      its accuracy. The response time of the experimental models depended on the outlet
      resistance of the exit ports and the volume of the collecting tube. In two
      models, this time was comparable with that of currently used volume-based
      electronic flow meters (approximately 2 seconds). In healthy volunteers, the
      maximum flow rates graded with the selected prototype and those measured with the
      rotating disk flow meter showed good agreement (difference=0.4+/-2.6 mL/s; mean+/
      SD). The low-cost flow meter may be used repeatedly to grade the maximum flow
      rate at private and familiar locations (for example, at home), which may increase
      the accuracy of evaluating the urinary stream in patients with lower urinary
      tract symptoms.

PMID- 11835425
TI  - Selective suppression of sphincter activation during sacral anterior nerve root
      stimulation.
AB  - The purpose of this work was to electrically activate small-diameter motor fibers
      in the sacral anterior roots innervating the urinary bladder, without activating
      the large-diameter fibers to the sphincter. Quasitrapezoidal current pulses were
      applied through tripolar spiral nerve electrodes on selected anterior sacral
      roots during acute experiments on eight dogs, maintained under pentobarbital
      anesthesia. Pressures were recorded from the bladder and sphincter with catheter
      mounted gauges. Stimulation with biphasic quasitrapezoidal pulses showed decrease
      in sphincter recruitment with increasing pulse amplitudes. The minimum current
      amplitude that resulted in maximum sphincter suppression was used to stimulate
      the roots with trains of 20 Hz pulses, with 60 mL of saline filling the bladder.
      Pressures were also recorded when 100 micros rectangular pulse trains at 20 Hz,
      both continuous and intermittent, were applied. Trains of stimuli were applied
      before and after dorsal root rhizotomy. Suppression of sphincter activation was
      defined to be a percentage, [(Maximum pressure -Minimum pressure)/Maximum
      pressure x100. The results from 22 roots in eight animals show that with single
      pulses, the average percentage suppression of sphincter activation was 76.3% (+/
      14.0). The minimum current for maximum sphincter suppression was 1.29 mA (+/
      0.62). The average bladder pressure evoked was 50 cm of water during pulse train
      stimulation, with no significant difference due to pulse type. With pulse trains,
      the sphincter pressures were significantly higher when the bladder was filled.
      Evacuation of fluid occurred in three animals with average flow rates of 1.0
      mL/s.

PMID- 11835426
TI  - Neurological signs are common in patients with urodynamically verified
      "idiopathic" bladder overactivity.
AB  - Overactive bladder dysfunction is an expression of defective neuromuscular
      control of the lower urinary tract. The causes and the way to classify this
      problem are currently under debate. In some patients the overactive bladder is
      one sign of a neurological disorder, in so called "idiopathic detrusor
      instability" the cause is less obvious. That an overactive bladder has a
      neurogenic cause is a reasonable hypothesis. We made a detailed neurological
      investigation in 45 patients with idiopathic overactive bladder. Cerebrospinal
      fluid (CSF) was examined and blood tests for vitamin B(12)and folic acid
      deficiency were checked, too. In 37 of the 45 patients (82%) pathological signs
      were observed in the neurological tests. The most common finding was central or
      peripheral paresis of the legs appearing in 24 patients (53%). Of the 45
      patients, eight received a neurological diagnosis, definite or possible MS or
      dorsal column sensation neuropathy. The results of this study give an indication
      of the importance of the neurological examination and suggest that neuropathy
      might not be uncommon in patients with so-called idiopathic detrusor instability.
      This also invites to reconsideration of the current classification. It is
      possible that a new classification based on a functional view could provide a
      better fundament in the search of etiologic and pathogenetic factors and also
      guide in the selection of the treatment most optimal for the individual patient.

PMID- 11835427
TI  - A new enzymic method for the isolation and culture of human bladder body smooth
      muscle cells.
AB  - Cultured cells of the human urinary bladder smooth muscle are useful for
      investigating bladder function, but methods for culturing them are not well
      developed. We have now established a novel enzymic technique. The smooth muscle
      layer was separated out and incubated with 0.2% trypsin for 30 min at 37 degrees
      C. The samples were then minced and incubated with 0.1% collagenase for 30 min
      and centrifuged at 900 g. The pellets were resuspended in RPMI-1640 medium
      containing 10% fetal calf serum (FCS) and centrifuged at 250 g. The smooth muscle
      cells from the supernatant were cultured in RPMI-1640 containing 10% FCS. The
      cells grew to confluence after 7-10 days, forming the "hills and valleys" growth
      pattern characteristic of smooth muscle cells. Immunostaining with anti-alpha
      actin, anti-myosin, and anti-caldesmon antibodies demonstrated that 99% of the
      cells were smooth muscle cells. To investigate the pharmacological properties of
      the cultured cells, we determined the inhibitory effect of muscarinic receptor
      antagonists on the binding of [3H]N-methylscopolamine to membranes from cultured
      cells. The pKi values obtained for six antagonists agreed with the corresponding
      values for transfected cells expressing the human muscarinic M2 subtype.
      Furthermore, carbachol produced an increase in the concentration of cytoplasmic
      free Ca2+ an action that was blocked by 4-diphenylacetoxy-N-methylpiperidine
      methiodide, an M3 selective antagonist. This result suggests that these cells
      express functional M3 muscarinic receptors, in addition to M2 receptors. The
      subcultured cells therefore appear to be unaffected by our new isolation method.

PMID- 11835428
TI  - Physiologic bladder evacuation with selective sacral root stimulation: sinusoidal
      signal and organ-specific frequency.
AB  - In patients with spinal cord injury above S2, who characteristically have both
      detrusor hyperflexia and sphincteric spasm, sacral anterior root stimulation can
      evacuate the bladder, but sacral deafferentation is needed to eliminate the
      hyperreflexia for normal bladder filling. The common stimulation parameters for
      these patients activate the detrusor and the external urethral sphincter
      simultaneously (detrusor-sphincter dyssynergia), and the resultant post-stimulus
      voiding is not physiologic. We sought to determine organ-specific stimulation
      parameters. In 20 male dogs, the rectangular pulse and sinusoidal signal forms
      were evaluated with a variety of parameters for stimulation of S2 and S3 anterior
      roots extra- and intradurally (i.e., stimulation frequency and voltage, uni-
      versus bilateral electrode placement, and degree of bladder filling). New torpedo
      shaped bipolar electrodes were used, adjusted to neural diameter. The best
      results were recorded with intradural bilateral sinusoidal signal. Sphincteric
      fatigue was produced by pre-stimulating S2 with 104+/-17 Hz and 0.8+/-0.1 V for
      10 to 15 seconds before S3 stimulation. S3 stimulation with 16+/- 2.1 Hz and
      0.4+/-0.1 V evoked a detrusor pressure of 28.7+/-3.0 cm H2O above the sphincteric
      pressure. Selective anterior root stimulation with organ-specific stimulation
      parameters can effect initial sphincteric fatigue to achieve physiologic voiding.

PMID- 11835429
TI  - Actions of the new antimuscarinic compound Lu 25-109 on isolated human and pig
      detrusor.
AB  - The aim of this study was to evaluate the effects of a novel antimuscarinic
      agent, Lu 25-109, a partial M1 receptor agonist, and M2/M3 receptor antagonist in
      human and pig detrusor to establish its affinity for muscarinic receptors in
      human detrusor and parotid gland and to compare the results with those obtained
      with oxybutynin. Effects on the detrusor were determined as regards the ability
      to inhibit carbachol-induced contractions and contractions induced by electrical
      field stimulation (EFS). Radioligand binding studies were performed to assess the
      ability to displace quinuclidinyl benzilate (3H-QNB) from muscarinic receptors in
      the detrusor and parotid gland. Lu 25-109 produced a concentration-dependent
      rightward shift of the concentration-response curves for carbachol in both human
      and pig detrusor, the pK(b) values being 6.2+/-0.1 (n=6) and 5.8+/-0.3 (n=6).
      Corresponding values for oxybutynin were 7.9+/-0.1 (n=7) and 7.8+/-0.1 (n=6).
      Contractions induced by EFS in human detrusor were almost completely inhibited by
      100 micromol/L Lu 25-109 (84+/-4%; n=4). In contrast, EFS-induced contractions in
      pig detrusor were less sensitive to Lu 25-109, resulting in a final inhibition of
      32+/-6% (n=9) with the highest concentration used (100 micromol/L). This
      difference in effect between human and pig detrusor was not observed with
      oxybutynin. Radioligand binding experiments demonstrated a small difference in
      affinity for Lu 25-109 in the parotid gland compared with the bladder, the pKi
      values being 6.2+/-0.1 versus 6.5+/-0.1 (n=4). Corresponding values for
      oxybutynin were 8.5+/-0.1 versus 8.2+/-0.1 (n=4). The results show that Lu 25-109
      competitively and effectively antagonizes carbachol-induced contractions and
      contractions induced by EFS in human detrusor muscle. Even if Lu 25-109 were less
      potent than oxybutynin, it has an effect profile that makes it of interest to
      test its ability to counteract bladder overactivity in humans.

PMID- 11835431
TI  - Reporting clinical trials: full access to all the data.

PMID- 11835432
TI  - Methylphenidate to treat ADHD is not contraindicated in children with tics.

PMID- 11835433
TI  - Epidemiology of primary blepharospasm.
AB  - We review epidemiological data on primary blepharospasm (BSP). There is a large
      variation in the stated prevalence of BSP, with crude estimates ranging from 16
      to 133 per million in different studies. A large proportion of this variability
      may be the result of differences in physician education on BSP. Age and female
      gender may increase the risk of developing BSP. The few case-control studies
      focusing on adult dystonias including BSP showed an increased risk in association
      with family history of dystonia and/or postural tremor, prior head and face
      trauma, and prior eye disease (e.g., blepharitis and keratoconjunctivitis), and a
      decreased risk associated with cigarette smoking. No association was found with
      age-related medical conditions such as hypertension and diabetes, family history
      of parkinsonism, and a history of anxiety or depression. Broocks et al. [Am J
      Psychiatry, 1998;155:555-557] found a significantly higher frequency of obsessive
      compulsive symptoms in BSP than hemifacial spasm despite the clinical similarity.
      Among putative risk factors for BSP, age at onset, female gender, and prior head
      or face trauma may affect spread of dystonia to adjacent body regions. While
      limited, the body of epidemiological data support the idea that environmental and
      familial, possibly genetic, factors may both be important in the etiology of BSP.

PMID- 11835434
TI  - Neuroprotective effect of riluzole in a primate model of Parkinson's disease:
      behavioral and histological evidence.
AB  - Our study aimed to determine whether riluzole, which has shown efficacy as a
      disease-modifying agent in amyotrophic lateral sclerosis (ALS), is
      neuroprotective in a marmoset model of Parkinson's disease (PD). Reduction of
      energy demand by riluzole could be a rational neuroprotective strategy with good
      tolerability. The efficacy of riluzole was evaluated in marmosets by testing its
      ability to reduce MPTP-induced behavioral deficits and loss of dopaminergic
      nigral neurons. Marmosets were divided into two groups of four animals each:
      animals in Group 1 were injected twice with MPTP (2 mg/kg subcutaneous) and
      treated with riluzole (10 mg/kg per os b.i.d.), animals in Group 2 (controls)
      were injected with MPTP and with the vehicle of riluzole. A third group of
      marmosets which did not receive MPTP or riluzole drug was introduced for
      neurohistopathological studies (normal animals). Marmosets treated with riluzole
      preserved a better motor function and neurological performance through the 26
      days of assessment when compared with the controls. Histologically, there was
      sparing of TH- and Nissl-stained nigral neurons and of TH-stained terminals in
      the striatum and the putamen in the group treated with riluzole compared to the
      controls. We conclude that riluzole protects dopaminergic neurons and reduces
      behavioral deficits in a marmoset model of PD.

PMID- 11835435
TI  - Bimanual coordination in Parkinson's disease: deficits in movement frequency,
      amplitude, and pattern switching.
AB  - Six patients with idiopathic Parkinson's disease (PD) and six age-matched
      controls participated in a variety of rhythmic bimanual coordination tasks. The
      main goal of the task was to perform inphase or antiphase patterns of pronation
      and supination of the forearms at a specified tempo, and to switch from one
      pattern to the other upon presentation of a visual cue. The availability of
      advance information was varied to examine whether deficits would emerge under
      choice versus pre-cue constraints. In pre-cue conditions, the subjects knew in
      advance which hand would be cued to initiate pattern change. In choice
      conditions, the cued hand was not known until the imperative stimulus was
      presented. Overall, the PD patients made movements with significantly lower
      frequencies and smaller amplitudes relative to controls. Patients exhibited
      spontaneous pattern switching from antiphase to inphase at significantly lower
      movement frequencies than controls. During intentional switching trials, the
      control group was significantly faster at initiating pattern change. PD and
      control groups differed in the time to initiate pattern switching to a greater
      extent under choice conditions, suggesting that patients used advance information
      to increase the speed of their response. The control group exhibited a preference
      for spontaneous switching and intentional switching through the subdominant hand.
      Patients exhibited a switching preference using the impaired limb (whether or not
      it was subdominant). The control group made more correct responses when the
      subdominant side was either pre-cued or presented in choice conditions. The
      patients maintained the subdominant/impaired side advantage under pre-cue
      conditions but not choice. In the maintenance of rhythmic movement, individuals
      with PD were able to use advance information in terms of both speed and accuracy.

PMID- 11835436
TI  - Bimanual coordination deficits with Parkinson's disease: the influence of
      movement speed and external cueing.
AB  - Continuous coordinated movement of the upper limbs performed at different
      movement frequencies, and with different external timing conditions, was examined
      in individuals with Parkinson's disease (PD) and healthy, age- and gender-matched
      controls. Participants performed symmetric in-phase movements toward and away
      from the midline of the body, and isodirectional anti-phase movements at one of
      three metronome speeds (0.75, 1.25, and 1.75 Hz), and in two different auditory
      cueing conditions (cue present, cue absent). Measures of relative phase accuracy
      (absolute mean error) and stability (standard deviation) revealed that
      individuals with PD performed in-phase movements as well as the controls, while
      anti-phase movements were performed with greater mean error and variability. The
      adverse effects of PD on the anti-phase task were also reflected by freezing
      (8.1% of anti-phase trials) and hypometric deficits (5.1% of anti-phase trials)
      during movement. None of these PD-related impairments occurred during in-phase
      trials. The overall accuracy or stability of movement coordination was not
      improved with the presence of external pacing cues, suggesting that although
      execution impairments of individuals with PD may be dramatically influenced by
      attention, external cueing does not necessarily improve movement performance.

PMID- 11835437
TI  - Interaction of levodopa and cues on voluntary reaching in Parkinson's disease.
AB  - The bradykinesia associated with Parkinson's disease (PD) can be improved by both
      levodopa and the use of external cues. We examined the combined effect of
      levodopa and external cueing on the voluntary reaching movements of individuals
      with PD. Nine subjects with PD and nine matched controls were studied reaching to
      a ball target. Subjects with PD were studied after being off levodopa overnight
      and again on their morning dose. Kinematic data were collected as all subjects
      made both accurate and fast reaches under two different cue conditions: noncued
      (self-initiated) and cued (triggered by a light). Subjects with PD reached more
      slowly than controls under all conditions. PD subjects increased their reach
      velocity and decreased movement time after taking levodopa and also when moving
      to a cue. However, the effects of levodopa and cueing were not additive. Instead,
      levodopa improved reach velocity to a greater extent in the noncued vs. cued
      condition. We also found that levodopa improved accurate (self-paced) reaches
      more than fast reaches. These data suggest that levodopa may preferentially
      improve voluntary reaches that are more internally generated.

PMID- 11835438
TI  - Progression of dopaminergic degeneration in Parkinson's disease and atypical
      parkinsonism: a longitudinal beta-CIT SPECT study.
AB  - Atypical parkinsonian syndromes (APS) such as multiple system atrophy,
      progressive supranuclear palsy, and corticobasal degeneration are characterized
      by poor response to antiparkinsonian medication and rapid clinical deterioration.
      We used SPECT and [123I]beta-CIT as a label of dopamine transporters to study the
      progression of presynaptic dopaminergic degeneration in Parkinson's disease (PD)
      and APS. Twenty-four PD patients with short disease duration (2.4 +/- 1.5 years),
      12 PD patients with long disease duration (9.2 +/- 2.6 years), 10 patients with
      APS (disease duration 2.1 +/- 1.5 years), and nine patients with essential tremor
      (ET) underwent sequential [123I]beta-CIT SPECT imaging with an interval of 25.5
      +/- 10.3 (13-63) months. The age-related decline of striatal beta-CIT binding was
      studied cross-sectionally in 30 healthy subjects. The ratio of
      striatum/cerebellum -1 at 20 hours after tracer injection, reflecting specific-to
      nondisplaceable binding, was used as the primary SPECT outcome measure. At scan
      1, striatal beta-CIT binding was reduced in PD patients with short disease
      duration (-42% compared with age-corrected normal values) and long disease
      duration (-51%), and APS (-36%), but normal in ET. During the observation period
      striatal beta-CIT binding significantly declined in patients with APS (14.9% per
      year) and short duration PD (7.1% per year), whereas PD patients with long
      disease duration and patients with ET showed no significant change of striatal
      beta-CIT binding between scans 1 and 2. The relative annual reduction from age
      corrected normal values at the time of scan 1 was significantly higher in
      patients with APS than in PD patients with short disease duration (9.6 vs. 4.3%,
      P = 0.004). These results demonstrate a rapid decline of striatal beta-CIT
      binding in patients with atypical parkinsonian syndromes, exceeding the reduction
      in PD. The dopaminergic degeneration in PD appears to slow down during the course
      of the disease. SPECT with [123I]beta-CIT is a sensitive marker of disease
      progression in parkinsonian disorders.

PMID- 11835439
TI  - beta-Adrenergics enhance brain extraction of levodopa.
AB  - We sought to determine whether beta-adrenergic agonists enhance the brain
      extraction of L-dopa and L-leucine. Systemic administration of beta-adrenergic
      agonists increase brain concentrations of L-dopa and other large neutral amino
      acids (LNAA) in rats and monkeys and may improve symptoms and reduce daily L-dopa
      requirement in patients with Parkinson's disease. Cerebral blood flow (CBF) using
      [3H]nicotine and the extraction fraction of 14C-labeled L-dopa or L-leucine were
      measured simultaneously in various brain regions of conscious rats using the dual
      isotope indicator fractionation technique after intraperitoneal administration of
      isoproterenol (a peripheral nonselective beta-adrenergic agonist), or clenbuterol
      (a beta2-adrenergic agonist that crosses the blood-brain barrier), or beta
      adrenergic agonist preceded by nadolol (a peripheral nonselective beta-adrenergic
      antagonist), or saline vehicle. Both beta-adrenergic agonists increased regional
      brain extraction fraction of L-dopa and L-leucine tracers by 35-45%, without
      altering regional CBF. These changes were accompanied by about a 30% decrease in
      plasma branched chain LNAA concentrations. Nadolol blocked all these effects.
      beta-Adrenergic agonists increase the brain extraction of L-dopa and leucine,
      mainly by peripheral mechanisms that reduce the levels of other competing plasma
      LNAAs for transport. Thus, beta-adrenergic agonists might be useful in the
      treatment of patients with Parkinson's disease by enhancing delivery of L-dopa to
      the brain.

PMID- 11835440
TI  - Factors impacting on quality of life in Parkinson's disease: results from an
      international survey.
AB  - Current management guidelines for the treatment of patients with Parkinson's
      disease (PD) are limited due to the lack of knowledge of factors that influence
      health-related quality of life (HRQL). To assess the HRQL of people with PD, and
      to systematically identify and evaluate those factors (other than disease
      severity and medication, which could have an impact), we undertook a cross
      sectional, randomized selection, multicenter international survey of patients
      with PD, caregivers, and clinicians. Face-to-face interviews were conducted with
      subjects in six countries. Disease severity, medication, and other factors
      hypothesized to influence HRQL were assessed using a combination of specially
      developed questionnaires and validated instruments including the Parkinson's
      Disease Questionnaire-39 (HRQL), Hoehn and Yahr Stage (disease severity), and
      Beck's Depression Inventory (BDI; depression). Multiple linear regression models
      were used to demonstrate whether the factors investigated contribute
      significantly to HRQL. The results obtained indicated that Hoehn and Yahr stage
      and medication explained only 17.3% of the variability in HRQL of patients with
      PD, although both were significant (R(2) = 0.173, P < 0.05). Other factors
      increased the explanatory power to adjusted R(2) = 0.597, with BDI being the most
      significant predictor of variability in HRQL (adjusted R(2) = 0.582; P < 0.001),
      followed by "Satisfaction with the explanation of the condition at diagnosis" and
      "Current feelings of optimism" (both P < 0.05). These factors, in addition to
      disease severity and medication, explain 59.7% of the variability in HRQL across
      the population. In conclusion, depression (as measured by the BDI) in PD,
      "satisfaction with the explanation of the condition at diagnosis" and "current
      feelings of optimism" have a significant impact on HRQL. The completion of this
      initial analysis is the first step towards developing management guidelines that
      truly influence the HRQL of patients with PD.

PMID- 11835441
TI  - Quality of life outcomes following surgical treatment of Parkinson's disease.
AB  - We assessed the impact of surgical treatment of Parkinson's disease on quality of
      life using generic quality of life instruments and utility scores. The Medical
      Outcomes Study short form health survey SF-36 and Parkinson's Disease
      Questionnaire PDQ-39 were used before and 3-6 months after surgery to assess
      quality of life, and the results were converted into utility valuations. Ninety
      seven patients were studied; 33 underwent unilateral thalamotomy, 33 unilateral
      pallidotomy, 20 bilateral pallidotomy, six subthalamic nucleus (STN) lesions,
      four mixed lesions, and in one case bilateral STN stimulation. All dimensions of
      the SF-36 except role mental and mental health showed statistically significant
      improvement following surgery. The PDQ-39 recorded significant improvements in
      the mobility, stigma, and bodily discomfort dimensions. The rating scale and time
      trade-off scales showed statistically significant gains in utility of 8% and 3%,
      respectively. Gains were particularly marked in the bilateral pallidotomy group.
      Differences in patient characteristics and selection made direct comparisons
      between procedures unreliable. Quality of life in patients with advanced
      Parkinson's disease is amenable to measurement; such measurement provides
      tentative evidence of significant gains in quality of life following some
      neurosurgical procedures.

PMID- 11835442
TI  - Influence of pallidal stimulation and levodopa on gait and preparatory postural
      adjustments in Parkinson's disease.
AB  - In order to assess the influence of the bilateral internal globus pallidus (GPi)
      stimulation on gait and postural instability in Parkinson's disease (PD), we
      compared gait kinematic parameters and preparatory postural adjustments before
      and 3 months after stimulation in off- and on-drug conditions for seven patients.
      Gait kinematic parameters and displacements of centre of pressure (CP) and
      shoulder computed before a lateral raising task of the leg, were recorded using
      optoelectric Vicon system. Levodopa (L-dopa) induced a clear benefit for gait
      velocity (related to an increase of stride length) and also an increase of swing
      phase duration. GPi stimulation had a limited effect, since the increase of gait
      velocity was induced by a concomitant increase of stride length and cadence
      corresponding to a compensatory mechanism. The benefit on swing phase duration
      was also moderate. Displacements of CP were improved mainly by L-dopa. GPi
      stimulation and L-dopa had the same beneficial effect on the speed at which the
      CP was transferred back towards the support side, the ankle velocity, the onset
      time for ankle displacement, and the decrease of shoulder amplitude towards the
      support side, which reflects a better postural adjustment phase. This study,
      based on an objective method, revealed that chronic bilateral GPi stimulation may
      improve gait and preparatory postural adjustments in severe PD patients with a
      more limited effect than L-dopa.

PMID- 11835443
TI  - Toxicity of Annonaceae for dopaminergic neurons: potential role in atypical
      parkinsonism in Guadeloupe.
AB  - In the French West Indies there is an abnormally high frequency of levodopa
      resistant parkinsonism, suggested to be caused by consumption of fruit and
      infusions of tropical plants, especially Annona muricata (corossol, soursop). To
      determine whether toxic substances from this plant can cause the neuronal
      degeneration or dysfunction underlying the syndrome, we exposed mesencephalic
      dopaminergic neurons in culture to the total extract (totum) of alkaloids from
      Annona muricata root bark and to two of the most abundant subfractions,
      coreximine and reticuline. After 24 hours, 50% of dopaminergic neurons
      degenerated with 18 microg/ml totum, 4.3 microg/ml (13 microM) coreximine, or 100
      microg/ml (304 microM) reticuline. The effects of the alkaloid totum were not
      restricted to the population of dopaminergic cells since GABAergic neurons were
      also affected by the treatment. Nuclei in dying neurons showed DNA condensation
      or fragmentation, suggesting that neuronal death occurred by apoptosis. Cell
      death was not excitotoxic and did not require toxin uptake by the dopamine
      transporter. Neurodegeneration was attenuated by increasing the concentration of
      glucose in the culture medium, which also reduced the effect of the dopaminergic
      neurotoxin MPP+, a mitochondrial respiratory chain inhibitor. Toxin withdrawal
      after short-term exposure arrested cell death. Acute treatment with totum,
      coreximine, or reticuline reversibly inhibited dopamine uptake by a mechanism
      that was distinct from that causing neuronal death. GABA uptake was not reduced
      under the same conditions. This study suggests that alkaloids from A. muricata
      can modulate the function and the survival of dopaminergic nerve cells in vitro.
      It is therefore conceivable that repeated consumption could cause the neuronal
      dysfunction and degeneration underlying the West Indian parkinsonian syndrome.

PMID- 11835444
TI  - Vascular parkinsonism: clinical correlates predicting motor improvement after
      lumbar puncture.
AB  - Vascular parkinsonism (VP) is a poorly defined entity which has clinical, and
      perhaps pathological, overlap with other diagnoses. Although classical VP
      involves lesions of the basal ganglia, the majority of cases actually show
      diffuse subcortical white matter changes (SCWMC) on imaging. The exact
      pathologies of these white matter changes are debated and likely heterogeneous,
      but are generally thought to represent areas of chronic or recurrent partial
      ischemia. Cerebrospinal fluid (CSF) drainage is the treatment for NPH and has
      been reported to improve symptoms in some patients with idiopathic NPH and
      associated SCWMC. To determine whether historical, clinical, or radiographic
      factors predict improvement in VP patients after CSF drainage, we removed 35-40
      ml of CSF via lumbar punctures (LP) from 40 patients and compared responders with
      nonresponders for a variety of demographics, clinical features, and blindly
      interpreted magnetic resonance images (MRI). Fifteen patients (37.5%) reported
      "significant and irrefutable" gait improvement after LP. Twelve (30.0%) reported
      no effect and 13 (32.5%) reported mild or very transient improvement. Timed gait
      in a subset of patients improved (P < 0.05) immediately after LP. Clinically,
      improvement after CSF removal was predicted by any positive response to levodopa
      (P < 0.001), the lack of vertical gaze palsies (P < 0.05), the lack of a pure
      freezing gait (P < 0.05), and the lack of hypotensive episodes (P < 0.05).
      Blinded MRI interpretation did not find features which clearly predicted
      response. Some patients diagnosed with VP improved after LP. Clinically, these
      patients tended to resemble idiopathic PD, whereas nonresponders more closely
      resembled progressive supranuclear palsy (PSP). These results warrant further
      investigation and also raise the possibility of testing CSF drainage in patients
      with idiopathic PD complicated by SCWMC.

PMID- 11835445
TI  - Co-occurrence of infantile epileptic seizures and childhood paroxysmal
      choreoathetosis in one family: clinical, EEG, and SPECT characterization of
      episodic events.
AB  - The co-occurrence of infantile convulsions and childhood paroxysmal
      choreoathetosis (ICCA syndrome) has recently been reported in several families.
      The pattern of familial clustering observed is consistent with a single locus
      mutation which has been mapped onto the pericentromeric region of chromosome 16.
      We studied the main clinical, electroencephalogram (EEG), and single photon
      emission computed tomography (SPECT) characteristics of episodic events in a new
      family presenting clinical features similar to that described in the ICCA
      syndrome. In the first year of life, a mother and her two daughters suffered from
      rare afebrile seizures lasting from 30 seconds to 15 minutes. Ictal EEG recording
      in one daughter at 7 months of age showed bilateral polyspikes with a posterior
      predominance. In the three patients, epileptic seizures regressed within a few
      weeks, and never reoccurred. At the age of 7 and 12 years, respectively, the two
      daughters presented daily brief (20 seconds to 1 minute) involuntary
      choreoathetotic episodes. In 10 of these attacks, EEG did not show any
      epileptiform abnormalities. In both sisters, an ictal SPECT was performed during
      a choreoathetotic episode. Subtracting the ictal SPECT from the interictal SPECT
      coregistered to magnetic resonance imaging (MRI) revealed significant
      modifications in the local cerebral perfusion in the sensorimotor cortex, the
      supplementary motor areas, and pallidum. Carbamazepine completely suppressed
      paroxysmal dyskinesias. These observations, together with literature data,
      suggest that in this syndrome, depending on brain maturation, the same genetic
      abnormality may result in different paroxysmal neurological symptoms.

PMID- 11835446
TI  - Nonlinear sensory cortex response to simultaneous tactile stimuli in writer's
      cramp.
AB  - Writer's cramp is a task-specific dystonia that leads to involuntary hand
      postures during writing. Abnormalities of sensory processing may play a
      pathophysiological role in this disorder. Electrophysiology studies in a monkey
      model of focal dystonia have revealed de-differentiation of sensory maps and the
      existence of single cells in hand regions of area 3b with enlarged receptive
      fields that extend to the surfaces of more than one digit. These changes may lead
      to abnormal processing of simultaneous sensory inputs. To study abnormal
      processing of simultaneous sensory information in adult humans with writer's
      cramp, we used functional magnetic resonance imaging to compare the response in
      primary sensory cortex with simultaneous tactile stimulation of the index and
      middle finger, with the response to stimulation of each finger alone. We tested
      five patients with writer's cramp and seven unaffected (normal) subjects. In the
      normal subjects, a linear combination of the activation patterns for individual
      finger stimulation predicts the pattern of activity for combined stimulation with
      12% error. In writer's cramp patients, the linear combination predicted the
      combined stimulation pattern with 30% error. Results indicate a nonlinear
      interaction between the sensory cortical response to individual finger
      stimulation in writer's cramp. This altered interaction may contribute to the
      motor abnormalities.

PMID- 11835447
TI  - Effects of immobility on sensory and motor symptoms of restless legs syndrome.
AB  - Restless legs syndrome (RLS) is defined by an irresistible need to move
      associated with leg paresthesia. Two additional features are essential for
      diagnosis: (1) worsening of symptoms at rest with temporary relief by activity,
      and (2) worsening of symptoms during the evening and/or during the night. The
      suggested immobilization test (SIT) has been developed to evaluate the presence
      of these criteria. This test quantifies leg movements and leg discomfort during a
      1-hour period of immobility prior to bedtime. We used the SIT to evaluate the
      effects of immobility on leg discomfort and leg movements experienced by 19
      patients with RLS and 19 control subjects. Results show that immobility
      significantly worsens both leg discomfort and periodic leg movements (PLM) in
      patients with RLS but not in controls. Patients with RLS showed a higher leg
      discomfort score (32.6 +/- 15.1 mm vs. 5.7 +/- 7.9 mm; P < 0.00001), a greater
      maximum leg discomfort value (63.4 +/- 27.4 mm vs. 13.7 +/- 23.0 mm; P < 0.00001)
      and a greater PLM index (88.4 +/- 62.6 vs. 10.4 +/- 20.6; P < 0.00004) than
      control subjects. These results further validate the use of the SIT as a
      diagnostic and research tool for RLS and confirm the contention of the
      International RLS study group that RLS symptoms worsen at rest.

PMID- 11835448
TI  - In utero bacterial endotoxin exposure causes loss of tyrosine hydroxylase neurons
      in the postnatal rat midbrain.
AB  - We investigated whether in utero exposure to the Gram(-) bacteriotoxin
      lipopolysaccharide (LPS) induces dopamine (DA) neuron loss in rats. The
      proinflammatory cytokine tumor necrosis factor alpha (TNF-alpha) kills DA neurons
      and is elevated in the brains of patients with Parkinson's disease (PD). LPS is a
      potent inducer of TNF-alpha, and both are increased in the chorioamniotic
      environment of women who have bacterial vaginosis (BV) during pregnancy,
      suggesting that BV might interfere with the normal development of fetal DA
      neurons. Gravid female rats were injected intraperitoneally with either LPS or
      normal saline at embryonic day 10.5 and their pups were killed at postnatal day
      21. The brains of the pups were assessed for DA and TNF-alpha levels and DA cell
      counts in the mesencephalon using tyrosine hydroxylase immunoreactive (THir)
      cells as a DA neuron marker. Prenatal LPS exposure significantly reduced striatal
      DA (29%) and increased DA activity (72%) as well as TNF-alpha (101%).
      Stereological cell counts in the mesencephalon were also significantly reduced
      (27%) by prenatal LPS exposure. Prenatal exposure to LPS, as might occur in
      humans with BV, produces a significant loss of THir cells in rats that is still
      present 33 days following a single injection of LPS. Since this cell loss is well
      past the normal phase of DA neuron apoptosis that occurs in early postnatal life,
      rats so exposed may have a permanent loss of DA neurons, suggesting that prenatal
      infections may represent risk factors for PD.

PMID- 11835449
TI  - Bilateral subthalamic stimulation monotherapy in advanced Parkinson's disease:
      long-term follow-up of patients.
AB  - Bilateral subthalamic nucleus stimulation (STN-DBS) is used to improve
      parkinsonian symptoms and attenuate levodopa-induced motor complications. In some
      patients, such clinical improvement allows antiparkinsonian medication (ApMed)
      withdrawal. We show the clinical outcome at the long-term follow-up of patients
      with advanced Parkinson's disease (PD) in which STN-DBS was used in monotherapy,
      and compare the clinical results of patients without medication with those
      obtained in parkinsonian patients in which ApMed were reduced but could not be
      totally displaced after surgery. We analyzed clinical outcome of ten patients
      with PD in which all ApMed was withdrawn after bilateral subthalamic stimulation
      and 16 parkinsonian patients still taking antiparkinsonian medication after
      surgery. After 1.5 years, STN-DBS monotherapy produced UPDRS motor scores similar
      to those observed in the on-drug condition before surgery without the
      inconvenience of motor fluctuations and dyskinesias. No significant differences
      were seen in most of clinical outcome measures when comparing patients still
      taking ApMed with patients in STN-DBS monotherapy but a few patients still taking
      ApMed presented mild dyskinesias and motor fluctuations and patients with STN-DBS
      monotherapy did not. STN-DBS is useful in the treatment of advanced PD and in
      some patients it is possible to maintain this therapy alone in the long term. The
      therapeutic effect of STN-DBS on motor signs can be equipotent to that of
      levodopa with the additional benefit of avoiding motor fluctuations and
      dyskinesias.

PMID- 11835450
TI  - Postmortem analysis of bilateral subthalamic electrode implants in Parkinson's
      disease.
AB  - This is the second neuropathological report detailing bilateral electrodes
      targeting the subthalamic nucleus (STN) in idiopathic Parkinson's disease (PD).
      The patient presented with unilateral tremor-dominant parkinsonism. Bilateral STN
      stimulation was carried out 7 years later due to significant disease progression
      and severe motor fluctuations. The patient exhibited bilateral improvements in
      rigidity and bradykinesia both intraoperatively and postoperatively. The patient
      died 2 months later from aspiration pneumonia. Neuropathological examination
      confirmed both the diagnosis of PD and the electrode placements. The tip of the
      left electrode was located medially and posteriorly in the left STN and the tip
      of the right electrode entered the base of the thalamus/zona incerta immediately
      above the right STN. Tissue changes associated with the subthalamic electrode
      tracts included mild cell loss, astrogliosis, and some tissue vacuolation. Our
      postmortem analysis indicates little tissue damage associated with STN
      stimulation for PD.

PMID- 11835451
TI  - Chronic high-frequency globus pallidus internus stimulation in different types of
      dystonia: a clinical, video, and MRI report of six patients presenting with
      segmental, cervical, and generalized dystonia.
AB  - The results of deep brain stimulation (DBS) of the globus pallidus internus (Gpi)
      in six patients with generalized, focal, and segmental dystonia are presented.
      Pre- and postoperative assessments are given for one patient with generalized
      inherited dystonia and for five patients with idiopathic segmental or cervical
      dystonia. Clinical symptoms were evaluated before and 3-12 months after surgery
      using the Burke-Fahn-Marsden (BFM) dystonia rating scale for primary torsion
      dystonia and the Tsui scale for cervical dystonia. The Short-Form Health Survey
      (SF-36) was completed by each patient to document preoperative and postoperative
      health status. Also, neurological status was documented by video before and
      during chronic stimulation. Magnetic resonance imaging studies were performed to
      show the anatomical localization of the electrode leads. Five patients showed a
      progressive improvement within 7 days. One patient with cervical dystonia and
      Meige's syndrome showed no improvement for 3 months, but beneficial effects were
      observed after 12 months. On average, the BFM movement scale scores decreased by
      72.5% and Tsui scale scores by 63%. SF-36 showed an improvement in health status
      by an average of 36% according to eight different health categories. We conclude
      that chronic high-frequency Gpi stimulation in different types of dystonia is a
      very effective and safe treatment.

PMID- 11835452
TI  - Randomised, double-blind, placebo-controlled trial to assess the potential of
      cannabinoid receptor stimulation in the treatment of dystonia.
AB  - Cannabis may have medicinal uses in a variety of diseases. The neural mechanisms
      underlying dystonia involve abnormalities within the basal ganglia-in particular,
      overactivity of the lateral globus pallidus (GPl). Cannabinoid receptors are
      located presynaptically on GABA terminals within the GPi, where their activation
      reduces GABA reuptake. Cannabinoid receptor stimulation may thus reduce
      overactivity of the GPl and thereby reduce dystonia. A double-blind, randomised,
      placebo-controlled, crossover study using the synthetic cannabinoid receptor
      agonist nabilone in patients with generalised and segmental primary dystonia
      showed no significant reduction in dystonia following treatment with nabilone.

PMID- 11835453
TI  - Dystonia in spinocerebellar ataxia type 6.
AB  - Spinocerebellar ataxias are heterogeneous disorders with overlapping clinical
      features. Spinocerebellar ataxia-6 is a dominantly inherited condition
      characterized by relatively pure ataxia with a paucity of other manifestations
      including extrapyramidal findings. We report on two patients with genetically
      proven SCA-6 who had dystonia. One patient presented initially with dystonia,
      which remained the most disabling problem. Dystonia may occur in SCA-6 and can be
      disabling.

PMID- 11835454
TI  - Physiological assessment of paroxysmal dystonia secondary to subacute sclerosing
      panencephalitis.
AB  - We report on a 26-year-old woman with subacute sclerosing panencephalitis (SSPE)
      who presented with frequent paroxysmal dystonic posturing. Electroencephalogram
      demonstrated generalized 5 to 10-second episodes of high-amplitude (150-300
      microV) delta activity alternating with 10 to 20-second periods of theta activity
      (40-50 microV). The patient experienced episodes of dystonic posturing coinciding
      with the periods of delta activity. Ictal Tc-99m Ceretec SPECT demonstrated
      marked increased activity in the bilateral caudate (R>L). The frequency and
      amplitude of the episodes initially markedly improved after the addition of
      carbamazepine. We suggest that the movements seen in this case of SSPE may
      represent basal ganglia ictal activity.

PMID- 11835455
TI  - Secondary nonresponsiveness to botulinum toxin type A in patients with
      oromandibular dystonia.
AB  - Intramuscular injection of botulinum toxin type A is the treatment of choice for
      most cases of oromandibular dystonia. We report on five patients with
      oromandibular dystonia that developed secondary nonresponsiveness to botulinum
      toxin type A following multiple injections over a 6-year period.

PMID- 11835456
TI  - Botulinum toxin and short-term electrical stimulation in the treatment of equinus
      in cerebral palsy.
AB  - Intramuscular botulinum toxin type A (BT-A) has been shown to reduce spasticity
      and to improve gait in children with cerebral palsy. To determine whether the
      efficacy of BT-A may be enhanced by electrical stimulation, as suggested in focal
      dystonia or in adult spastic patients, 12 children with dynamic foot equinus
      deformity were randomly assigned to two groups in a blinded, clinically
      controlled trial. Intramuscular BT-A into calf muscles was followed by adjuvant
      electrical stimulation in Group A (n = 6) but not in Group B (n = 6). Clinical
      assessment and instrumented gait analysis were performed before and 1, 3, and 6
      months after treatment. The combined treatment of BT-A and electrical stimulation
      was not superior to BT-A alone. For all patients, improvement of the clinical and
      gait variables occurred at 1 and 3 months after BT-A injection.

PMID- 11835457
TI  - Botulinum toxin antibody type A titres after cessation of botulinum toxin
      therapy.
AB  - In some patients, therapy with botulinum toxin type A (BT-A) becomes ineffective
      due to formation of antibodies (BT-A-AB). The time course of BT-A-AB titres after
      cessation of BT-A therapy was quantitatively studied to determine whether and
      when they might drop. Thirteen patients (eight women, five men) with various
      dystonic syndromes and complete secondary therapy failure (CSTF) were included in
      this study (age at initiation of BT-A therapy, 48.2 +/- 11.3 years; number of
      injection series, 7.7 +/- 2.9; treatment time, 678.8 +/- 385.6 days; mean
      interinjection interval, 90.4 +/- 35.5 days; mean single dose, 546.7 +/- 336.9
      EMU; cumulative dose, 4185.1 +/- 3375.7 EMU [1 EMU = 1 botox MU = 3 dysport MU]).
      During a monitoring period of at least 750 days after occurrence of CSTF, two or
      more BT-A-AB tests using the quantitative mouse diaphragm assay were performed.
      Eight of 13 BT-A-AB titres decreased. The onset of decrease could be detected
      after between approximately 500 and 1,750 days. After 1,250 to 2,250 days they
      had dropped below a level of 0.002 U/ml, where CSTF is unlikely. Five of 13 BT-A
      AB titres did not decrease. For three of these five, the monitoring period was
      less than 1,500 days; a chance to drop remained. The other two were monitored for
      up to 2,400 days. Patients with decreasing and nondecreasing BT-A-AB titres did
      not exhibit statistically significant differences in either clinical
      characteristics or treatment parameters. When BT-A therapy was stopped the
      majority of BT-A-AB titres eventually decreased, allowing reinitiation of BT-A
      therapy. Application of new BT-A preparations with low antigenic potency might
      then become an interesting treatment option.

PMID- 11835458
TI  - Sixty-six-year-old woman with unexplained falls followed five years later by
      severe generalized myoclonus.

PMID- 11835459
TI  - Jules Bernard Luys and the subthalamic nucleus.
AB  - Jules Bernard Luys, a highly energetic French investigator who made important
      contributions to anatomopathology, clinical neurology, and psychiatry, discovered
      the subthalamic nucleus in 1865. Unfortunately, Luys' description of the nucleus
      that still bears his name, as well as his highly original insights on the role of
      this important motor structure, are rarely taken into account in the current
      thinking about the basal ganglia organization. Thus, we thought it of interest to
      review Luys' contribution to our knowledge of the subthalamic nucleus and also
      briefly examine the other remarkable achievements of this singular figure of 19th
      century neurology.

PMID- 11835460
TI  - Levodopa-induced ocular dyskinesias in Parkinson's disease.
AB  - Levodopa-induced ocular dyskinesias are very uncommon. Usually they occur
      simultaneously with limb peak-dose choreatic dyskinesias. We report on a patient
      with leftward and upward deviations of gaze during the peak effect of levodopa,
      and hypothesize that a severe dopaminergic denervation in the caudate nucleus is
      needed for the appearance of these levodopa-induce ocular dyskinesias.

PMID- 11835461
TI  - Levodopa-induced dyskinesias and continuous subcutaneous infusions of
      apomorphine: results of a two-year, prospective follow-up.
AB  - Twelve patients with levodopa-induced dyskinesias were treated with continuous
      subcutaneous apomorphine. A markedly significant reduction in peak dose
      dyskinesias occurred over a two-year follow-up.

PMID- 11835462
TI  - Postural asymmetries following unilateral subthalomotomy for advanced Parkinson's
      disease.
AB  - Two cases of postural asymmetries following unilateral stereotaxic subthalamotomy
      were observed with head and body tilting to the side contralateral to the STN
      lesion, which corrected itself completely or partially with levodopa treatment.
      After subsequent contralateral STN surgery, the postural asymmetry disappeared in
      both patients. Possible mechanism is discussed.

PMID- 11835463
TI  - Life-threatening parkinsonism induced by kava-kava.
AB  - We present a 45-year-old female with severe parkinsonism induced by kava-kava.
      The patient, who had a family history of essential tremor, developed severe and
      persistent parkinsonism after days of treatment with kava extract for anxiety.
      The symptoms improved with anticholinergics. Kava derivatives could produce
      severe parkinsonism in individuals with genetic susceptibility.

PMID- 11835464
TI  - Late-onset axial jerky dystonia due to the DYT1 deletion.
AB  - We describe a 71-year-old woman who presented to the neurology department late in
      life with a jerky axial dystonia due to the DYT1 GAG deletion. She recalled that
      her symptoms began 62 years prior to study and remained unchanged for 40 years,
      illustrating the broad phenotype of DYT1 idiopathic torsion dystonia.

PMID- 11835465
TI  - Riluzole therapy in cervical dystonia.
AB  - We conducted a 6-week open-label pilot study with blinded video rating of
      riluzole (50 mg twice a day) in six patients with cervical dystonia (CD)
      refractory to botulinum toxin A and oral pharmacological treatment. The Tsui
      rating scale served as primary efficacy measure and improved significantly under
      riluzole (P = 0.002). In three of six patients, the Tsui score improved by more
      than 30% with a greater 50% reduction in the head tremor/jerk subscore of the
      Tsui scale. These data suggest that riluzole may be helpful in a subgroup of
      patients with disabling CD refractory to other therapies.

PMID- 11835466
TI  - X-linked dystonia ("Lubag") presenting predominantly with parkinsonism: a more
      benign phenotype?
AB  - "Lubag," or Filipino X-linked dystonia, typically presents with either pure
      dystonia (that inexorably becomes generalized) or combined dystonia-parkinsonism.
      We report on three cases of Lubag presenting with isolated parkinsonism without
      dystonia or late-onset dystonia and a slower course.

PMID- 11835467
TI  - Encephalomyelitis with rigidity complicating human immunodeficiency virus
      infection.
AB  - A 34-year-old man with human immunodeficiency virus type 1 (HIV-1) presented with
      axial rigidity, painful spasms, and delayed hemiparesis and dementia.
      Cerebrospinal fluid analysis showed no antiglutamic acid dehydrogenase antibodies
      but viral genome from Epstein-Barr virus was detected by polymerase chain
      reaction. Clinical features and possible viral aetiology of progressive
      encephalomyelitis with rigidity are briefly discussed.

PMID- 11835468
TI  - Improvement of severe trunk spasms by bilateral high-frequency stimulation of the
      motor thalamus in a patient with chorea-acanthocytosis.
AB  - We report on a patient with a severe form of chorea-acanthocytosis, intractable
      to medical treatment, who benefited from bilateral high-frequency stimulation
      (HFS) of the posterior ventral oral nucleus of the thalamus. The frequency of
      trunk spasms dramatically decreased after surgery and the clinical benefit
      remained stable 1 year later. However, no clear effect was observed on dysarthria
      nor on hypotonia, which always impaired gait. We propose that HFS of the motor
      thalamus is a potential treatment for choreic or truncal dystonic symptoms
      whenever hypotonia is not the main feature of the syndrome.

PMID- 11835470
TI  - Focal pathological startle following pontine infarction.
AB  - A 36-year-old male developed an acute right-sided weakness due to left-sided
      pontine infarction. Two months later, he first noticed sudden right elbow flexion
      in response to a loud unexpected noise. Detailed electrophysiological assessment
      was performed. A large, short-latency (median 39 msec), synchronous
      electromyographic discharge occurred in the right biceps brachii electrodes
      following a 50-msec, 120-dB 1-kHz tone burst, with habituation only with very
      short (30-second) interstimulus intervals. Less synchronous activity at longer
      latencies was present both in a number of right-sided arm muscles at rest and on
      the clinically unaffected side during a tonic voluntary contraction. We discuss
      possible underlying mechanisms and our reasons for considering this a focally
      enhanced startle response. Our report broadens the range of expression of
      acquired startle disorders.

PMID- 11835469
TI  - Intracortical inhibition is reduced in a patient with a lesion in the
      posterolateral thalamus.
AB  - We describe a patient who developed a complex movement disorder following an
      ischemic lesion in the right posterolateral thalamus. Transcranial magnetic
      stimulation showed a shortening of the cortical silent period and deficient
      cortico-cortical inhibition using paired magnetic pulses on the affected side,
      indicating reduced effectiveness of intracortical inhibitory mechanisms.

PMID- 11835472
TI  - Risperidone and Parkinson's disease.

PMID- 11835471
TI  - Objective tinnitus associated with essential laryngeal myoclonus: report of two
      cases.
AB  - We report on two patients with an objective tinnitus. In the first one, the
      objective tinnitus was unique as it was due to bilateral rhythmic contractions of
      the vocal cords. In the second, the objective tinnitus arose from Eustachian tube
      contractions and was associated with up and down movements of the larynx. In both
      patients, the abnormal laryngeal movement shared most of the characteristics of
      palatal or palatolaryngeal myoclonus and was thought to be laryngeal myoclonus.
      Its origin remained essential as all the investigations were negative.

PMID- 11835473
TI  - The straight dope on addiction to dopamimetic drugs.

PMID- 11835474
TI  - Cervical dystonia.

PMID- 11835476
TI  - Critical assessment of methods of protein structure prediction (CASP): round IV.

PMID- 11835477
TI  - Prediction targets of CASP4.

PMID- 11835478
TI  - Processing and evaluation of predictions in CASP4.
AB  - The Livermore Prediction Center conducted the target collection and prediction
      submission processes for Critical Assessment of Protein Structure Prediction
      (CASP4) and Critical Assessment of Fully Automated Structure Prediction Methods
      (CAFASP2). We have also evaluated all the submitted predictions using criteria
      and methods developed during the course of three previous CASP experiments and
      preparation for CASP4. We present an overview of the implemented system.
      Particular attention is paid to newly developed evaluation techniques and data
      presentation schemes. With the rapid increase in CASP participation and in the
      number of submitted predictions, special emphasis is placed on methods allowing
      reliable pre-classification of submissions and on techniques useful in automated
      evaluation of predictions. We also present an overview of our website, including
      target structures, predictions, and their evaluations (
      http://predictioncenter.llnl.gov).

PMID- 11835479
TI  - Analysis and assessment of comparative modeling predictions in CASP4.
AB  - We describe here the results of our analysis of the comparative modeling
      predictions submitted to the fourth round of Critical Assessment of Structure
      Prediction (CASP4). On the basis of a numerical evaluation of the models, we
      assessed their ability to predict the overall fold correctly, the relative
      orientation of domains in multidomain proteins, the conformation of the side
      chains, the loop regions, and the biologically important residues of the targets.
      We also discuss the performance of automatic prediction servers and compare the
      results of CASP4 with those obtained in CASP3.

PMID- 11835480
TI  - Enhancement of protein modeling by human intervention in applying the automatic
      programs 3D-JIGSAW and 3D-PSSM.
AB  - Fourteen models were constructed and analyzed for the comparative modeling
      section of Critical Assessment of Techniques for Protein Structure Prediction
      (CASP4). Sequence identity between each target and the best possible parent(s)
      ranged between 55 and 13%, and the root-mean-square deviation between model and
      target was from 0.8 to 17.9 A. In the fold recognition section, 10 of the 11
      remote homologues were recognized. The modeling protocols are a combination of
      automated computer algorithms, 3D-JIGSAW (for comparative modeling) and 3D-PSSM
      (for fold recognition), with human intervention at certain critical stages. In
      particular, intervention is required to check superfamily assignment, best
      possible parents from which to model, sequence alignments to those parents and
      take-off regions for modeling variable regions. There now is a convergence of
      algorithms for comparative modeling and fold recognition, particularly in the
      region of remote homology.

PMID- 11835481
TI  - Comparative modeling of CASP4 target proteins: combining results of sequence
      search with three-dimensional structure assessment.
AB  - Comparative modeling aims at constructing molecular models for proteins of
      unknown structure, by using known structures of related proteins as templates. To
      test the comparative modeling approach reported here, predictions for 13 target
      proteins were submitted during the fourth round of "blind" protein structure
      prediction experiment (CASP4; http://PredictionCenter.llnl.gov/casp4). Sequence
      identity between these target proteins and the closest known structures ranged
      from 13 to 58%, indicating a broad spectrum of prediction difficulty. Although
      this broad difficulty range required addressing a variety of issues, the most
      important proved to be sequence-structure alignment for distant homology targets.
      The alignment step was based on structure-based evaluation of alignment variants
      produced mainly with PSI-BLAST intermediate sequence search procedure (PSI-BLAST
      ISS). Although a fraction of correctly aligned residues in resulting models was
      markedly better than the average in all cases, for distant homology targets it
      was still considerably below the estimated achievable level. Results with CASP4
      targets show that, along with the correctness of sequence-structure alignments,
      effective use of multiple template structures may significantly increase accuracy
      of the model structure. Improvement in this area should also result in more
      accurate loop modeling and side-chain prediction.

PMID- 11835482
TI  - Assessment of the CASP4 fold recognition category.
AB  - We present the assessment of the CASP4 fold recognition category. The tasks we
      had to execute include the splitting of multidomain targets into single domains,
      the classification of target domains in terms of prediction categories, the
      numerical evaluation of predictions, the mapping of numerical scores to quality
      indices, the ranking of predictors, the selection of top-performing groups, and
      the analysis and critical discussion of the state of the art in this field. The
      125 fold recognition groups were assessed by a total score that summarizes their
      performance over all targets and a quality score reflecting the average quality
      of the submitted models. Most of the top-performing groups achieved respectable
      results on both scores simultaneously. Several groups submitted models that were
      much closer to the respective target structures than any of the known folds in
      the Protein Data Bank. The CASP4 assessment included the automated servers of the
      parallel CAFASP experiment. For the total score, the highest rank achieved by a
      fully automated server is 12. Two thirds of the predictors have rather low
      scores.

PMID- 11835483
TI  - Fold recognition from sequence comparisons.
AB  - We applied a new protocol based on PSI-Blast to predict the structures of fold
      recognition targets during CASP4. The protocol used a back-validation step to
      infer biologically significant connections between sequences with PSI-Blast E
      values up to 10. If connections were found to proteins of known structure,
      alignments were generated by using HMMer. The protocol was implemented in a fully
      automated version (SBauto) and in a version that allowed manual intervention
      (SBfold). We found that the automated version made 17 predictions for target
      domains, of which 8 identified the correct fold with an average alignment
      accuracy of 24% for alignable residues and 43% for equivalent secondary structure
      elements. The manual version improved predictions somewhat, with 10 of 15
      predictions identifying the correct fold with alignment accuracies of 33% for
      alignable residues and 64% for equivalent secondary structure elements. We
      describe successes and failures of our approach and discuss future developments
      of fold recognition.

PMID- 11835484
TI  - CASP2 knowledge-based approach to distant homology recognition and fold
      prediction in CASP4.
AB  - In 1996, in CASP2, we presented a semimanual approach to the prediction of
      protein structure that was aimed at the recognition of probable distant homology,
      where it existed, between a given target protein and a protein of known structure
      (Murzin and Bateman, Proteins 1997; Suppl 1:105-112). Central to our method was
      the knowledge of all known structural and probable evolutionary relationships
      among proteins of known structure classified in the SCOP database (Murzin et al.,
      J Mol Biol 1995;247:536-540). It was demonstrated that a knowledge-based approach
      could compete successfully with the best computational methods of the time in the
      correct recognition of the target protein fold. Four years later, in CASP4, we
      have applied essentially the same knowledge-based approach to distant homology
      recognition, concentrating our effort on the improvement of the completeness and
      alignment accuracy of our models. The manifold increase of available sequence and
      structure data was to our advantage, as well as was the experience and expertise
      obtained through the classification of these data. In particular, we were able to
      model most of our predictions from several distantly related structures rather
      than from a single parent structure, and we could use more superfamily
      characteristic features for the refinement of our alignments. Our predictions for
      each of the attempted distant homology recognition targets ranked among the few
      top predictions for each of these targets, with the predictions for the
      hypothetical protein HI0065 (T0104) and the C-terminal domain of the ABC
      transporter MalK (T0121C) being particularly successful. We also have attempted
      the prediction of protein folds of some of the targets tentatively assigned to
      new superfamilies. The average quality of our fold predictions was far less than
      the quality of our distant homology recognition models, but for the two targets,
      chorismate lyase (T0086) and Appr>p cyclic phosphodiesterase (T0094), our
      predictions achieved the top ranking.

PMID- 11835485
TI  - What is the value added by human intervention in protein structure prediction?
AB  - This article presents results of blind predictions submitted to the CASP4 protein
      structure prediction experiment. We made two sets of predictions: one using the
      fully automated SAM-T99 server and one using the improved SAM-T2K method with
      human intervention. Both methods use iterative hidden Markov model-based methods
      for constructing protein family profiles, using only sequence information.
      Although the SAM-T99 method is purely sequence based, the SAM-T2K method uses the
      predicted secondary structure of the target sequence and the known secondary
      structure of the templates to improve fold recognition and alignment. In this
      article, we try to determine what aspects of the SAM-T2K method were responsible
      for its significantly better performance in the CASP4 experiment in the hopes of
      producing a better automatic prediction server. The use of secondary structure
      prediction seems to be the most valuable single improvement, though the combined
      total of various human interventions is probably at least as important.

PMID- 11835486
TI  - Sequence-structure homology recognition by iterative alignment refinement and
      comparative modeling.
AB  - Our approach to fold recognition for the fourth critical assessment of techniques
      for protein structure prediction (CASP4) experiment involved the use of the FUGUE
      sequence-structure homology recognition program (http://www
      cryst.bioc.cam.ac.uk/fugue), followed by model building. We treat models as
      hypotheses and examine these to determine whether they explain the available
      data. Our method depends heavily on environment-specific substitution tables
      derived from our database of structural alignments of homologous proteins
      (HOMSTRAD, http://www-cryst.bioc.cam.ac.uk/homstrad/). FUGUE uses these tables to
      incorporate structural information into profiles created from HOMSTRAD alignments
      that are matched against a profile created for the target from multiple sequence
      alignment. In addition, environment-specific substitution tables are used
      throughout the modeling procedure and as part of the model evaluation. Annotation
      of sequence alignments with JOY, to reflect local structural features, proved
      valuable, both for modifying hypotheses, and for rejecting predictions when the
      expected pattern of conservation is not observed. Our stringency in rejecting
      incorrect predictions led us to submit a relatively small number of models,
      including only a low number of false positives, resulting in a high average
      score.

PMID- 11835487
TI  - Assessment of novel fold targets in CASP4: predictions of three-dimensional
      structures, secondary structures, and interresidue contacts.
AB  - In the Novel Fold category, three types of predictions were assessed: three
      dimensional structures, secondary structures, and residue-residue contacts. For
      predictions of three-dimensional models, CASP4 targets included 5 domains or
      structures with novel folds, and 13 on the borderline between Novel Fold and Fold
      Recognition categories. These elicited 1863 predictions of these and other
      targets by methods more general than comparative modeling or fold recognition
      techniques. The group of Bonneau, Tsai, Ruczinski, and Baker stood out as
      performing well with the greatest consistency. In many cases, several groups were
      able to predict fragments of the target correctly-often at a level somewhat
      larger than standard supersecondary structures-but were not able to assemble
      fragments into a correct global topology. The methods of Bonneau, Tsai,
      Ruczinski, and Baker have been successful in addressing the fragment assembly
      problem for many but not all the target structures.

PMID- 11835488
TI  - Rosetta in CASP4: progress in ab initio protein structure prediction.
AB  - Rosetta ab initio protein structure predictions in CASP4 were considerably more
      consistent and more accurate than previous ab initio structure predictions. Large
      segments were correctly predicted (>50 residues superimposed within an RMSD of
      6.5 A) for 16 of the 21 domains under 300 residues for which models were
      submitted. Models with the global fold largely correct were produced for several
      targets with new folds, and for several difficult fold recognition targets, the
      Rosetta models were more accurate than those produced with traditional fold
      recognition models. These promising results suggest that Rosetta may soon be able
      to contribute to the interpretation of genome sequence information.

PMID- 11835489
TI  - Predicting novel protein folds by using FRAGFOLD.
AB  - The results of applying a fragment-based protein tertiary structure prediction
      method to the prediction of 8 CASP4 targets are described. The method is based on
      the assembly of supersecondary structural fragments taken from highly resolved
      protein structures using a simulated annealing algorithm. Despite the significant
      degree of success in this case, there is clearly much more developmental work
      required before predictions with the accuracy of a good homology model, or even a
      good fold recognition model, can be made with use of this kind of approach.

PMID- 11835490
TI  - Protein structure prediction using a combination of sequence-based alignment,
      constrained energy minimization, and structural alignment.
AB  - We present a novel approach to protein structure prediction in which fold
      recognition techniques are combined with ab initio folding methods. Based on the
      predicted secondary structure, one of two different protocols is followed. For
      mostly alpha proteins, global optimization and sampling of a statistical energy
      function is used to generate many low-energy structures; these structures are
      then screened against a fold library. Any structural matches are then selected
      for further refinement. For proteins predicted to have significant beta-content,
      sequence and secondary structure-based alignment is used to identify candidate
      templates; spatial constraints are then extracted from these templates and used,
      along with the statistical energy function, in the global sampling and
      optimization program. Successes and failures of both protocols are discussed.

PMID- 11835491
TI  - Application of PROSPECT in CASP4: characterizing protein structures with new
      folds.
AB  - In the Fourth Community Wide Experiment on the Critical Assessment of Techniques
      for Protein Structure Prediction (CASP4), we predicted all 43 targets using our
      threading application PROSPECT. PROSPECT guarantees to find an optimal alignment
      between a protein sequence and a structural fold for a general energy function
      with pairwise contact potential. For each prediction, it gives a reliability
      assessment based on a neural network approach. In addition, PROSPECT has been
      added to the Genomic Integrated Supercomputing Toolkit (GIST) and is deployed on
      terascale computing resources. Structural predictions in CASP4 included three
      categories, that is comparative modeling, fold recognition, and prediction for
      structures with new folds. In the fold recognition category, PROSPECT correctly
      identified 8 of a total of 22 and finished the sixth in the total scores among
      127 assessed groups. In the "new fold" category, it found important structural
      features for most targets, and its overall performance is among the best of all
      prediction methods. Our CASP4 performance demonstrates that PROSPECT is a
      powerful tool to quickly characterize structures with new folds, and it may
      provide useful structural restraints for ab initio prediction methods.

PMID- 11835492
TI  - Ab initio protein structure prediction via a combination of threading, lattice
      folding, clustering, and structure refinement.
AB  - A combination of sequence comparison, threading, lattice, and off-lattice Monte
      Carlo (MC) simulations and clustering of MC trajectories was used to predict the
      structure of all (but one) targets of the CASP4 experiment on protein structure
      prediction. Although this method is automated and is operationally the same
      regardless of the level of uniqueness of the query proteins, here we focus on the
      more difficult targets at the border of the fold recognition and new fold
      categories. For a few targets (T0110 is probably the best example), the ab initio
      method produced more accurate models than models obtained by the fold recognition
      techniques. For the most difficult targets from the new fold categories,
      substantial fragments of structures have been correctly predicted. Possible
      improvements of the method are briefly discussed.

PMID- 11835493
TI  - Progress in predicting inter-residue contacts of proteins with neural networks
      and correlated mutations.
AB  - This article presents recent progress in predicting inter-residue contacts of
      proteins with a neural network-based method. Improvement over the results
      obtained at the previous CASP3 competition is attained by using as input to the
      network a complex code, which includes evolutionary information, sequence
      conservation, correlated mutations, and predicted secondary structures. The
      predictor was trained and cross-validated on a data set comprising the contact
      maps of 173 non-homologous proteins as computed from their well-resolved three
      dimensional structures. The method could assign protein contacts with an average
      accuracy of 0.21 and with an improvement over a random predictor of a factor
      greater than 6, which is higher than that previously obtained with methods only
      based either on neural networks or on correlated mutations. Although far from
      being ideal, these scores are the highest reported so far for predicting protein
      contact maps. On 29 targets automatically predicted by the server (CORNET) the
      average accuracy is 0.14. The predictor is poorly performing on all alpha
      proteins, not represented in the training set. On all beta and mixed proteins (22
      targets) the average accuracy is 0.16. This set comprises proteins of different
      complexity and different chain length, suggesting that the predictor is capable
      of generalization over a broad number of features.

PMID- 11835494
TI  - Comparison of performance in successive CASP experiments.
AB  - As the number of completed CASP (Critical Assessment of Protein Structure
      Prediction) experiments grows, so does the need for stable, standard methods for
      comparing performance in successive experiments. It is critical to develop
      methods for determining the areas in which there is progress and in which areas
      are static. We have added an analysis of the CASP4 results to that previously
      published for CASPs 1, 2, and 3. We again use a unified difficulty scale to
      permit comparison of performance as a function of target difficulty in the
      different CASPs. The scale is used to compare performance in aligning target
      sequences to a structural template. There was a clear improvement in alignment
      quality between CASP1 (1994) and CASP2 (1996). No change is apparent between
      CASP2 and CASP3 (1998). There is a small barely detectable improvement between
      CASP3 and the latest experiment (CASP4, 2000). Alignment remains the major source
      of error in all models based on less than about 30% sequence identity. Comparison
      of performance in the new fold modeling regime is complicated by issues in
      devising an objective target difficulty scale. We have found limited numerical
      support for significant progress between CASP3 and CASP4 in this area. More
      subjectively, most observers are convinced that there has been substantial
      progress. Progress is dominated by a single group.

PMID- 11835495
TI  - CAFASP2: the second critical assessment of fully automated structure prediction
      methods.
AB  - The results of the second Critical Assessment of Fully Automated Structure
      Prediction (CAFASP2) are presented. The goals of CAFASP are to (i) assess the
      performance of fully automatic web servers for structure prediction, by using the
      same blind prediction targets as those used at CASP4, (ii) inform the community
      of users about the capabilities of the servers, (iii) allow human groups
      participating in CASP to use and analyze the results of the servers while
      preparing their nonautomated predictions for CASP, and (iv) compare the
      performance of the automated servers to that of the human-expert groups of CASP.
      More than 30 servers from around the world participated in CAFASP2, covering all
      categories of structure prediction. The category with the largest participation
      was fold recognition, where 24 CAFASP servers filed predictions along with 103
      other CASP human groups. The CAFASP evaluation indicated that it is difficult to
      establish an exact ranking of the servers because the number of prediction
      targets was relatively small and the differences among many servers were also
      small. However, roughly a group of five "best" fold recognition servers could be
      identified. The CASP evaluation identified the same group of top servers albeit
      with a slightly different relative order. Both evaluations ranked a semiautomated
      method named CAFASP-CONSENSUS, that filed predictions using the CAFASP results of
      the servers, above any of the individual servers. Although the predictions of the
      CAFASP servers were available to human CASP predictors before the CASP submission
      deadline, the CASP assessment identified only 11 human groups that performed
      better than the best server. Furthermore, about one fourth of the top 30
      performing groups corresponded to automated servers. At least half of the top 11
      groups corresponded to human groups that also had a server in CAFASP or to human
      groups that used the CAFASP results to prepare their predictions. In particular,
      the CAFASP-CONSENSUS group was ranked 7. This shows that the automated
      predictions of the servers can be very helpful to human predictors. We conclude
      that as servers continue to improve, they will become increasingly important in
      any prediction process, especially when dealing with genome-scale prediction
      tasks. We expect that in the near future, the performance difference between
      humans and machines will continue to narrow and that fully automated structure
      prediction will become an effective companion and complement to experimental
      structural genomics.

PMID- 11835496
TI  - LiveBench-2: large-scale automated evaluation of protein structure prediction
      servers.
AB  - The aim of LiveBench is to provide a continuous evaluation of structure
      prediction servers to inform developers and users about the current state-of-the
      art structure prediction tools. LiveBench differs from other evaluation
      experiments because it is a large-scale and a fully automated procedure. Since
      LiveBench-1, which finished in April 2000, and related but independent CASP3 and
      CAFASP1 experiments, significant progress in the field has occurred. Some of the
      new developments have already been assessed at the recent CASP4 and CAFASP2
      experiments (both independently of LiveBench), but others have not been observed
      yet because they entail developments carried out only recently. These include the
      availability of new servers (Pcons, FUGUE, and Coblath) and the enhancement of
      previously existing tools (mGenThreader, Sam-T, and 3D-PSSM), which illustrate
      the fast rate at which the field is advancing. Consequently, to keep in pace with
      the development, we present the results of the second large-scale evaluation of
      protein structure prediction servers. Of the 11 fold recognition servers
      evaluated, two servers appear to be most sensitive. One of these is 3D-PSSM, a
      server significantly improved after LiveBench-1. The other top performer is the
      new consensus server Pcons, which significantly outperformed other servers in the
      specificity of predictions. LiveBench-2 shows that the top performing servers are
      able to accurately recognize a fold for about one third of the "difficult"
      targets, a clear improvement over LiveBench-1 results. Given that automated
      structure prediction is increasingly becoming a biologists companion, the
      guidelines drawn from the LiveBench experiments are likely to provide users with
      valuable and timely information for their prediction needs.

PMID- 11835498
TI  - Review of the sixth Annual Johns Hopkins Folding Meeting.

PMID- 11835497
TI  - EVA: large-scale analysis of secondary structure prediction.
AB  - EVA is a web-based server that evaluates automatic structure prediction servers
      continuously and objectively. Since June 2000, EVA collected more than 20,000
      secondary structure predictions. The EVA sets sufficed to conclude that the field
      of secondary structure prediction has advanced again. Accuracy increased
      substantially in the 1990s through using evolutionary information taken from the
      divergence of proteins in the same structural family. Recently, the evolutionary
      information resulting from improved searches and larger databases has again
      boosted prediction accuracy by more than 4% to its current height around 76% of
      all residues predicted correctly in one of the three states: helix, strand, or
      other. The best current methods solved most of the problems raised at earlier
      CASP meetings: All good methods now get segments right and perform well on
      strands. Is the recent increase in accuracy significant enough to make
      predictions even more useful? We believe the answer is affirmative. What is the
      limit of prediction accuracy? We shall see. All data are available through the
      EVA web site at [cubic.bioc.columbia.edu/eva/]. The raw data for the results
      presented are available at [eva]/sec/bup_common/2001_02_22/.

PMID- 11835499
TI  - Predicting the disulfide bonding state of cysteines using protein descriptors.
AB  - Knowledge of the disulfide bonding state of the cysteines of proteins is of major
      interest in designing numerous molecular biology experiments, or in predicting
      their three-dimensional structure. Previous methods using the information gained
      from aligned sets of sequences have reached up to 82% of success in predicting
      the oxidation state of cysteines. In the present study, we assess the relative
      efficiency of different descriptors in predicting the cysteine disulfide bonding
      states. Our results suggest that the information on the residues flanking the
      cysteines is less informative about the disulfide bonding state than about the
      amino acid content of the whole protein. Using a combination of logistic
      functions learned with subsets of proteins homogeneous in terms of their amino
      acid content, we propose a simple prediction approach, starting from a single
      sequence, that reaches success rates close to 84%. This score can be improved by
      avoiding predictions regarding cysteines for which the decision is not well
      marked. For example, we obtain a score close to 87% correct prediction when we
      exclude predicting 10% of the cysteines.

PMID- 11835500
TI  - Essential domain motions in barnase revealed by MD simulations.
AB  - The wealth of data accumulated on the bacterial ribonuclease barnase is
      complemented by molecular dynamics trajectories starting from four different
      experimental structures and covering a total of >10 ns. Using principal component
      analysis, the simulations are interpreted in view of dynamic domains and hinges
      promoting relative motions of these domains. Two domains with residues 7-22 and
      52-108 for the first domain and residues 25-51 for the second domain were
      consistently observed. Hinge regions consist primarily of Tyr24, Ser50, Ile51,
      and Gly52. Earlier mutation studies have demonstrated that the residues of the
      hinge regions play essential roles for the stability and activity of barnase. The
      domain motions are correlated to inter-domain interactions involving functionally
      important active site residues, such as Lys27 and Glu73. A model is presented
      that combines the observation of dynamic domains and their motions with the
      extensive mutation data from the literature. Enthalpic energy contributions
      originating from specific inter-domain interactions as well as entropic energy
      contributions due to the domain motions are discussed in the frame of this model
      and compared with destabilization energies measured for corresponding mutants.

PMID- 11835501
TI  - Stability and conformational dynamics of metallothioneins from the antarctic fish
      Notothenia coriiceps and mouse.
AB  - The structural properties and the conformational dynamics of antarctic fish
      Notothenia coriiceps and mouse metallothioneins were studied by Fourier-transform
      infrared and fluorescence spectroscopy. Infrared data revealed that the secondary
      structure of the two metallothioneins is similar to that of other
      metallothioneins, most of which lack periodical secondary structure elements such
      as alpha-helices and beta-sheets. However, the infrared spectra of the N.
      coriiceps metallothionein indicated the presence of a band, which for its typical
      position in the spectrum and for its sensitivity to temperature was assigned to
      alpha-helices whose content resulted in 5% of the total secondary structure of
      the protein. The short alpha-helix found in N. coriiceps metallothionein showed
      an onset of denaturation at 30 degrees C and a T(m) at 48 degrees C. The data
      suggest that in N. coriiceps metallothionein a particular cysteine is involved in
      the alpha-helix and in the metal-thiolate complex. Moreover, infrared spectra
      revealed that both proteins investigated possess a structure largely accessible
      to the solvent. The time-resolved fluorescence data show that N. coriiceps
      metallothionein possesses a more flexible structure than mouse metallothionein.
      The spectroscopic data are discussed in terms of the biological function of the
      metallothioneins.

PMID- 11835502
TI  - The leghemoglobin proximal heme pocket directs oxygen dissociation and stabilizes
      bound heme.
AB  - Sperm whale myoglobin (Mb) and soybean leghemoglobin (Lba) are two small,
      monomeric hemoglobins that share a common globin fold but differ widely in many
      other aspects. Lba has a much higher affinity for most ligands, and the two
      proteins use different distal and proximal heme pocket regulatory mechanisms to
      control ligand binding. Removal of the constraint provided by covalent attachment
      of the proximal histidine to the F-helices of these proteins decreases oxygen
      affinity in Lba and increases oxygen affinity in Mb, mainly because of changes in
      oxygen dissociation rate constants. Hence, Mb and Lba use covalent constraints in
      opposite ways to regulate ligand binding. Swapping the F-helices of the two
      proteins brings about similar effects, highlighting the importance of this helix
      in proximal heme pocket regulation of ligand binding. The F7 residue in Mb is
      capable of weaving a hydrogen-bonding network that holds the proximal histidine
      in a fixed orientation. On the contrary, the F7 residue in Lba lacks this
      property and allows the proximal histidine to assume a conformation favorable for
      higher ligand binding affinity. Geminate recombination studies indicate that heme
      iron reactivity on picosecond timescales is not the dominant cause for the
      effects observed in each mutation. Results also indicate that in Lba the proximal
      and distal pocket mutations probably influence ligand binding independently.
      These results are discussed in the context of current hypotheses for proximal
      heme pocket structure and function.

PMID- 11835503
TI  - 3',5' Cyclic nucleotide phosphodiesterases class III: members, structure, and
      catalytic mechanism.
AB  - 3',5' Cyclic nucleotide phosphodiesterases (PDEs) comprise a superfamily of
      enzymes that were previously divided by their primary structure into two major
      classes: PDE class I and II. The 3',5' cyclic AMP phosphodiesterase from
      Escherichia coli encoded by the cpdA gene does not show any homology to either
      PDE class I or class II enzymes and, therefore, represents a new, third class of
      PDEs. Previously, information about essential structural elements, substrate and
      cofactor binding sites, and the mechanism of catalysis was unknown for this
      enzyme. The present study shows by computational analysis that the enzyme encoded
      by the E. coli cpdA gene belongs to a family of phosphodiesterases that closely
      resembles the catalytic machinery known from purple acid phosphatases and several
      other dimetallophosphoesterases. They share both the conserved sequence motif, D
      (X)(n) GD-(X)(n)-GNH[E/D]-(X)(n)-H-(X)(n)-GHXH, which contains the invariant
      residues forming the active site of purple acid phosphatases, a binuclear Fe(3+)
      Me(2+)-containing center, as well as a beta(alpha)beta(alpha)beta motif as a
      typical secondary structure signature. Furthermore, the known biochemical
      properties of the bacterial phosphodiesterase encoded by the cpdA gene, such as
      the requirement of iron ions and a reductant for maintaining its catalytic
      activity, support this hypothesis developed by computational analysis. In
      addition, the availability of atomic coordinates for several purple acid
      phosphatases and related proteins allowed the generation of a three-dimensional
      model for class III cyclic nucleotide phosphodiesterases.

PMID- 11835504
TI  - Molecular dynamics study of a hyperthermophilic and a mesophilic rubredoxin.
AB  - In recent years, increased interest in the origin of protein thermal stability
      has gained attention both for its possible role in understanding the forces
      governing the folding of a protein and for the design of new highly stable
      engineered biocatalysts. To study the origin of thermostability, we have
      performed molecular dynamics simulations of two rubredoxins, from the mesophile
      Clostridium pasteurianum and from the hyperthermophile Pyrococcus furiosus. The
      simulations were carried out at two temperatures, 300 and 373 K, for each
      molecule. The length of the simulations was within the range of 6-7.2 ns. The
      rubredoxin from the hyperthermophilic organism was more flexible than its
      mesophilic counterpart at both temperatures; however, the overall flexibility of
      both molecules at their optimal growth temperature was the same, despite 59%
      sequence homology. The conformational space sampled by both molecules was larger
      at 300 K than at 373 K. The essential dynamics analysis showed that the principal
      overall motions of the two molecules are significantly different. On the
      contrary, each molecule showed similar directions of motion at both temperatures.

PMID- 11835505
TI  - Docking multiple conformations of a flexible ligand into a protein binding site
      using NMR restraints.
AB  - A method is described for docking a large, flexible ligand using intra-ligand
      conformational restraints from exchange-transferred NOE (etNOE) data. Numerous
      conformations of the ligand are generated in isolation, and a subset of
      representative conformations is selected. A crude model of the protein-ligand
      complex is used as a template for overlaying the selected ligand structures, and
      each complex is conformationally relaxed by molecular mechanics to optimize the
      interaction. Finally, the complexes were assessed for structural quality.
      Alternative approaches are described for the three steps of the method:
      generation of the initial docking template; selection of a subset of ligand
      conformations; and conformational sampling of the complex. The template is
      generated either by manual docking using interactive graphics or by a
      computational grid-based search of the binding site. A subset of conformations
      from the total number of peptides calculated in isolation is selected based on
      either low energy and satisfaction of the etNOE restraints, or a cluster analysis
      of the full set. To optimize the interactions in the complex, either a restrained
      Monte Carlo-energy minimization (MCM) protocol or a restrained simulated
      annealing (SA) protocol were used. This work produced 53 initial complexes of
      which 8 were assessed in detail. With the etNOE conformational restraints, all of
      the approaches provide reasonable models. The grid-based approach to generate an
      initial docking template allows a large volume to be sampled, and as a result,
      two distinct binding modes were identified for a fifteen-residue peptide binding
      to an enzyme active site.

PMID- 11835506
TI  - Thermal unfolding molecular dynamics simulation of Escherichia coli dihydrofolate
      reductase: thermal stability of protein domains and unfolding pathway.
AB  - Temperature induced unfolding of Escherichia coli dihydrofolate reductase was
      carried out by using molecular dynamic simulations. The simulations show that the
      unfolding generally involves an initial end-to-end collapse of the adenine
      binding domain into partially extended loops, followed by a gradual breakdown of
      the remaining beta sheet core structure. The core, which consists of beta strands
      5-7, was observed to be the most resistant to thermal unfolding. This region,
      which is made up of part of the N terminus domain and part of the large domain of
      the E. coli dihydrofolate reductase, may constitute the nucleation site for
      protein folding and may be important for the eventual formation of both domains.
      The unfolding of different domains at different stages of the unfolding process
      suggests that protein domains vary in stability and that the rate at which they
      unfold can affect the overall outcome of the unfolding pathway. This observation
      is compared with the recently proposed hierarchical folding model. Finally, the
      results of the simulation were found to be consistent with a previous
      experimental study (Frieden, Proc Natl Acad Sci USA 1990;87:4413-4416) which
      showed that the folding process of E. coli dihydrofolate reductase involves
      sequential formation of the substrate binding sites.

PMID- 11835507
TI  - Structure and cooperativity of a T-state mutant of histidine decarboxylase from
      Lactobacillus 30a.
AB  - Histidine decarboxylase (HDC) from Lactobacillus 30a converts histidine to
      histamine, a process that enables the bacteria to maintain the optimum pH range
      for cell growth. HDC is regulated by pH; it is active at low pH and inactive at
      neutral to alkaline pH. The X-ray structure of HDC at pH 8 revealed that a helix
      was disordered, resulting in the disruption of the substrate-binding site. The
      HDC trimer has also been shown to exhibit cooperative kinetics at neutral pH,
      that is, histidine can trigger a T-state to R-state transition. The D53,54N
      mutant of HDC has an elevated Km, even at low pH, indicating that the enzyme
      assumes the low activity T-state. We have solved the structures of the D53,54N
      mutant at low pH, with and without the substrate analog histidine methyl ester
      (HME) bound. Structural analysis shows that the apo-D53,54N mutant is in the
      inactive or T-state and that binding of the substrate analog induces the enzyme
      to adopt the active or R-state. A mechanism for the cooperative transition is
      proposed.

PMID- 11835508
TI  - A study on protein sequence alignment quality.
AB  - One of the most central methods in bioinformatics is the alignment of two protein
      or DNA sequences. However, so far large-scale benchmarks examining the quality of
      these alignments are scarce. On the other hand, recently several large-scale
      studies of the capacity of different methods to identify related sequences has
      led to new insights about the performance of fold recognition methods. To
      increase our understanding about fold recognition methods, we present a large
      scale benchmark of alignment quality. We compare alignments from several
      different alignment methods, including sequence alignments, hidden Markov models,
      PSI-BLAST, CLUSTALW, and threading methods. For most methods, the alignment
      quality increases significantly at about 20% sequence identity. The difference in
      alignment quality between different methods is quite small, and the main
      difference can be seen at the exact positioning of the sharp rise in alignment
      quality, that is, around 15-20% sequence identity. The alignments are improved by
      using structural information. In general, the best alignments are obtained by
      methods that use predicted secondary structure information and sequence profiles
      obtained from PSI-BLAST. One interesting observation is that for different pairs
      many different methods create the best alignments. This finding implies that if a
      method that could select the best alignment method for each pair existed, a
      significant improvement of the alignment quality could be gained.

PMID- 11835509
TI  - Crystal structure of human nucleoside diphosphate kinase A, a metastasis
      suppressor.

PMID- 11835510
TI  - Why protein R-factors are so large: a self-consistent analysis.
AB  - The R-factor and R-free are commonly used to measure the quality of protein
      models obtained in X-ray crystallography. Well-refined protein structures usually
      have R-factors in the range of 20-25%, whereas intrinsic errors in the
      experimental data are usually around 5%. We use molecular dynamics simulations to
      perform a self-consistent analysis by which we determine the major factors
      contributing to large values of protein R-factors. The analysis shows that
      significant R-factor values can arise from the use of isotropic B-factors to
      model anisotropic protein motions and from coordinate errors. Even in the absence
      of coordinate errors, the use of isotropic B-factors can cause the R-factors to
      be around 10%; for coordinate errors smaller than 0.2 A, the two errors types
      make similar contributions. The inaccuracy of the energy function used and
      multistate protein dynamics are unlikely to make significant contributions to the
      large R-factors.

PMID- 11835511
TI  - Classification of the caspase-hemoglobinase fold: detection of new families and
      implications for the origin of the eukaryotic separins.
AB  - A comprehensive sequence and structural comparative analysis of the caspase
      hemoglobinase protein fold resulted in the delineation of the minimal structural
      core of the protease domain and the identification of numerous, previously
      undetected members, including a new protease family typified by the HetF protein
      from the cyanobacterium Nostoc. The first bacterial homologs of legumains and
      hemoglobinases were also identified. Most proteins containing this fold are known
      or predicted to be active proteases, but multiple, independent inactivations were
      noticed in nearly all lineages. Together with the tendency of caspase-related
      proteases to form intramolecular or intermolecular dimers, this suggests a
      widespread regulatory role for the inactive forms. A classification of the
      caspase-hemoglobinase fold was developed to reflect the inferred evolutionary
      relationships between the constituent protein families. Proteins containing this
      domain were so far detected almost exclusively in bacteria and eukaryotes. This
      analysis indicates that caspase-hemoglobinase-fold proteases and their
      inactivated derivatives are widespread in diverse bacteria, particularly those
      with a complex development, such as Streptomyces, Anabaena, Mesorhizobium, and
      Myxococcus. The eukaryotic separin family was shown to be most closely related to
      the mainly prokaryotic HetF family. The phyletic patterns and evolutionary
      relationships between these proteins suggest that they probably were acquired by
      eukaryotes from bacteria during the primary, promitochondrial endosymbiosis. A
      similar scenario, supported by phylogenetic analysis, seems to apply to
      metacaspases and paracaspases, with the latter, perhaps, being acquired in an
      independent horizontal transfer to the eukaryotes. The acquisition of the caspase
      hemoglobinase-fold domains by eukaryotes might have been critical in the
      evolution of important eukaryotic processes, such as mitosis and programmed cell
      death.

PMID- 11835512
TI  - Toward minimalist models of larger proteins: a ubiquitin-like protein.
AB  - Our recently developed off-lattice bead model capable of simulating protein
      structures with mixed alpha/beta content has been extended to model the folding
      of a ubiquitin-like protein and provides a means for examining the more complex
      kinetics involved in the folding of larger proteins. Using trajectories generated
      from constant-temperature Langevin dynamics simulations and sampling with the
      multiple multi-histogram method over five-order parameters, we are able to
      characterize the free energy landscape for folding and find evidence for folding
      through compact intermediates. Our model reproduces the observation that the C
      terminus loop structure in ubiquitin is the last to fold in the folding process
      and most likely plays a spectator role in the folding kinetics. The possibility
      of a productive metastable intermediate along the folding pathway consisting of
      collapsed states with no secondary structure, and of intermediates or transition
      structures involving secondary structural elements occurring early in the
      sequence, is also supported by our model. The kinetics of folding remain multi
      exponential below the folding temperature, with glass-like kinetics appearing at
      T/T(f) approximately 0.86. This new physicochemical model, designed to be
      predictive, helps validate the value of modeling protein folding at this level of
      detail for genomic-scale studies, and motivates further studies of other protein
      topologies and the impact of more complex energy functions, such as the addition
      of solvation forces.

PMID- 11835513
TI  - Folding and stability of the three-stranded beta-sheet peptide Betanova: insights
      from molecular dynamics simulations.
AB  - The dynamics of the three-stranded beta-sheet peptide Betanova has been studied
      at four different temperatures (280, 300, 350, and 450 K by molecular dynamics
      simulation techniques, in explicit water. Two 20-ns simulations at 280 K indicate
      that the peptide remains very flexible under "folding" conditions sampling a
      range of conformations that together satisfy the nuclear magnetic resonance (NMR)
      derived experimental constraints. Two simulations at 300 K (above the
      experimental folding temperature) of 20 ns each show partial formation of
      "native"-like structure, which also satisfies most of the NOE constraints at 280
      K. At higher temperature, the presence of compact states, in which a series of
      hydrophobic contacts remain present, are observed. This is consistent with
      experimental observations regarding the role of hydrophobic contacts in
      determining the peptide's stability and in initiating the formation of turns and
      loops. A set of different structures is shown to satisfy NMR-derived distance
      restraints and a possible mechanism for the folding of the peptide into the NMR
      determined structure is proposed.

PMID- 11835515
TI  - Automated assignment of SCOP and CATH protein structure classifications from FSSP
      scores.
AB  - We present an automated procedure to assign CATH and SCOP classifications to
      proteins whose FSSP score is available. CATH classification is assigned down to
      the topology level, and SCOP classification is assigned to the fold level.
      Because the FSSP database is updated weekly, this method makes it possible to
      update also CATH and SCOP with the same frequency. Our predictions have a nearly
      perfect success rate when ambiguous cases are discarded. These ambiguous cases
      are intrinsic in any protein structure classification that relies on structural
      information alone. Hence, we introduce the "twilight zone for structure
      classification." We further suggest that to resolve these ambiguous cases, other
      criteria of classification, based also on information about sequence and
      function, must be used.

PMID- 11835514
TI  - From structure to function: YrbI from Haemophilus influenzae (HI1679) is a
      phosphatase.
AB  - The crystal structure of the YrbI protein from Haemophilus influenzae (HI1679)
      was determined at a 1.67-A resolution. The function of the protein had not been
      assigned previously, and it is annotated as hypothetical in sequence databases.
      The protein exhibits the alpha/beta-hydrolase fold (also termed the Rossmann
      fold) and resembles most closely the fold of the L-2-haloacid dehalogenase (HAD)
      superfamily. Following this observation, a detailed sequence analysis revealed
      remote homology to two members of the HAD superfamily, the P-domain of Ca(2+)
      ATPase and phosphoserine phosphatase. The 19-kDa chains of HI1679 form a tetramer
      both in solution and in the crystalline form. The four monomers are arranged in a
      ring such that four beta-hairpin loops, each inserted after the first beta-strand
      of the core alpha/beta-fold, form an eight-stranded barrel at the center of the
      assembly. Four active sites are located at the subunit interfaces. Each active
      site is occupied by a cobalt ion, a metal used for crystallization. The cobalt is
      octahedrally coordinated to two aspartate side-chains, a backbone oxygen, and
      three solvent molecules, indicating that the physiological metal may be
      magnesium. HI1679 hydrolyzes a number of phosphates, including 6-phosphogluconate
      and phosphotyrosine, suggesting that it functions as a phosphatase in vivo. The
      physiological substrate is yet to be identified; however the location of the gene
      on the yrb operon suggests involvement in sugar metabolism.

PMID- 11835516
TI  - Accumbens activity during a multiple schedule for water and sucrose reinforcement
      in rats.
AB  - Electrophysiological recording procedures were used to examine nucleus accumbens
      (Acb) cell firing during operant responding for water reinforcement vs. a highly
      palatable sweet solution (0.6 M sucrose). Rats (n = 8) were trained on a multiple
      schedule to press one lever for water (fixed ratio 1, FR1; 15 min) followed by a
      20-sec timeout period (chamber dark, levers retracted), and extension of a second
      spatially distinct lever that the animals pressed for sucrose reinforcement (FR1;
      15 min). Of 84 cells, 55 neurons (65%) displayed one of three types of patterned
      discharges (increases or decreases in firing rate) immediately before or
      following the sucrose- or water-reinforced response. The major finding of this
      report was that the majority of these neurons (36/55 cells; 65%) showed similar
      types of neuronal firing patterns across the two reinforcer conditions. The
      remaining cells (19/55; 35%) exhibited patterned activity specific to responding
      for one reinforcer only (water or sucrose). These findings are discussed with
      respect to how Acb neurons encode goal-directed behaviors for "natural"
      reinforcers including food, water, and a palatable sweet solution.

PMID- 11835517
TI  - Excitatory and inhibitory responses of dopamine neurons in the ventral tegmental
      area to nicotine.
AB  - In the present electrophysiological study the mechanisms by which nicotine
      activates dopamine neurons in the ventral tegmental area in anesthetized Sprague
      Dawley rats were analyzed. Intravenous administration of nicotine caused a dose
      dependent increase in firing rate and percentage of spikes fired in bursts of
      ventral tegmental area dopamine neurons. However, this activation was preceded by
      an instantaneous but short-lasting inhibition of the firing rate. The excitation
      of dopamine neurons by nicotine (1.5-400 microg/kg i.v.) was antagonized and even
      reversed into an inhibitory response by elevated levels (four-fold) of the
      endogenous glutamate receptor antagonist kynurenic acid, as induced by a potent
      inhibitor of kynurenine 3-hydroxylase (PNU 156561A, 40 mg/kg, i.v., 5-9 h). The
      antagonistic action induced by PNU 156561A pretreatment was prevented by
      administration of D-cycloserine (128 mg/kg, i.v., 5 min). Administration of the
      GABA(B)-receptor antagonist CGP 35348 (200 mg/kg, i.v., 3 min) facilitated the
      nicotine-induced increase in burst firing activity of dopamine neurons and
      antagonized the short-lasting decrease in firing rate by nicotine. The results of
      the present study show that nicotine produces both inhibition and excitation of
      ventral tegmental area dopamine neurons, actions that appear to be related to the
      release of GABA and glutamate, respectively. Whereas the excitatory action of
      nicotine may be associated with motivational processes underlying learning and
      cognitive behavior, the inhibitory action of the drug may play a more prominent
      role in the situation of a profound dysregulation of the mesocorticolimbic
      dopamine system and may help to explain the high prevalence of tobacco-smoking in
      schizophrenics.

PMID- 11835518
TI  - Evidence for activation of histamine H3 autoreceptors during handling stress in
      the prefrontal cortex of the rat.
AB  - On-line microdialysis of histamine in 10-min samples of the prefrontal cortex of
      the conscious rat is described. The HPLC-fluorescent assay for histamine in
      dialysates has been significantly simplified by using only one postcolumn reagent
      line instead of the three reagent lines described in earlier methods. The method
      is selective, sensitive (detection limit: 2-3 fmol on column), and linear over a
      large concentration range. Basal values of histamine decreased to about 50% of
      basal levels during infusion of tetrodotoxin (5 x 10(-6) M). Handling rats for 15
      min increased histamine in dialysates to about 300% of basal levels. When
      tetrodotoxin (10(-6) M) was applied during handling the increase in histamine
      release was strongly (about 80%) suppressed. The handling-induced increase in
      histamine was used as a paradigm to investigate the functional activity of
      histamine H3 autoreceptors during mild stress or arousal. An H3 receptor specific
      agonist (alpha-methylhistamine; 10(-5) M) and antagonist (thioperamide; 10(-5) M)
      were infused into the frontal cortex via the microdialysis probe. The effect of
      handling on histamine release was potentiated during infusion of thioperamide and
      fully suppressed during infusion of alpha-methylhistamine. These results clearly
      illustrate the efficacy of the H3 autoreceptor in modulating stimulated histamine
      release during natural stimulatory conditions.

PMID- 11835520
TI  - Neuronal differentiation and synapse formation occur in space and time with
      fractal dimension.
AB  - The analysis of a set of experimental data obtained by an independent team of
      researchers confirms that neuronal differentiation or synapse formation do occur
      in time and space with fractal dimension. The interacting cells create first a
      dynamic system with its own attractor, (i.e., a fragment of time and space where
      the dynamic processes occur and where no further evolution of the system is
      possible at all owing to the action of the intrasystemic forces unless some
      extrasystemic forces act upon it). This attractor is then modified in the active
      manner by the differentiating cells until the system attains a degenerated
      stationary state and differentiation ends. The fractal structure of the system is
      also lost in the course of tumor progression. Our data indicate that the cellular
      system can attain the degenerated stationary state, leaving the attractor with a
      fractal dimension directly or undergoing diversification into many attractors and
      going through the areas of deterministic chaos. Since evolution of the cellular
      system is driven by the cooperative dynamic processes, as reflected by the
      changes of the mean fractal dimension between the intervals of the Gompertzian
      curve, it is likely that cells differentiate into neurons and create synapses
      with a conjugated probability and non-Gaussian distribution rather than with the
      classical probability and the Gaussian distribution. These findings can help to
      optimize features of artificial neural networks. They also define a simple in
      vitro biological model for biophysical and biochemical studies on natural neural
      networks.

PMID- 11835519
TI  - Kainate-induced currents in rat cortical neurons in culture are modulated by
      riluzole.
AB  - The action of the neuroprotective and anticonvulsant agent riluzole on kainate
      induced currents was studied in rat cortical neurons in primary culture by using
      the whole-cell configuration of the patch-clamp technique. Kainate elicited
      macroscopic, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)-sensitive inward
      currents in all the patched cells and the amplitude of the current was
      concentration-dependent (EC50= 106 microM). Riluzole decreased the inward
      currents induced by 100 microM kainate at all holding potentials and the
      reduction was dose-dependent (IC50= 101 microM). The maximal response to kainate
      decreased in the presence of 50 microM riluzole, without changing its EC50,
      indicating a noncompetitive mechanism of inhibition. The amplitude of the
      responses induced by kainate under control conditions and during riluzole was a
      linear function of the membrane potential and the reversal potential of the
      currents was not significantly different in the two experimental conditions.
      Instead, the total conductance of the cell membrane for the currents induced by
      100 microM kainate was significantly reduced in the presence of 50 microM
      riluzole (P < 0.05). The analysis of the kainate membrane current noise performed
      under control conditions and during perfusion of 100 microM riluzole revealed
      that riluzole reduced the probability of kainate-activated ionic channels to be
      in the open state. Conversely, the unitary conductance of channels, as well as
      their characteristic time constant, seemed to be unchanged. These results reveal
      an additional mechanism by which riluzole can interact with glutamatergic
      neurotransmission and provides further support for the idea that riluzole may
      prove beneficial in the treatment of central nervous system injuries involving
      the excitotoxic actions of glutamate.

PMID- 11835521
TI  - Synthesis and evaluation of [18F]fluoroethyl SA4503 as a PET ligand for the sigma
      receptor.
AB  - The sigma receptor might be involved in several diseases in the central nervous
      system. It occurs in the endocrine, immune, and other peripheral organ systems
      and is expressed in a variety of human tumors. The [18F]fluoroethyl analog of the
      sigma1-selective ligand SA4503 ([18F]FE-SA4503) was prepared and evaluated in
      animals to investigate its suitability for in vivo measurement of sigma receptors
      with positron emission tomography (PET). [18F]FE-SA4503 was synthesized by
      [18F]fluoroethylation of the corresponding O-demethyl precursor in an overall
      radiochemical yield of 4-7% (EOB) with a specific activity of >100 TBq/mmol. The
      radioligand had higher in vitro affinity for the sigma receptor than SA4503
      (IC(50) sigma1 6.48 nM, IC50 sigma2 2.11 nM). [18F]FE-SA4503 was injected into
      mice. Uptake could be blocked by co-injection of the sigma receptor ligands
      haloperidol, pentazocine, and cold SA4503, but not with other receptor ligands.
      Ex vivo autoradiography studies in rats showed regional distribution in the brain
      similar to [11C]SA4503. Hippocampus, thalamus, and cortical areas were clearly
      delineated by [18F]FE-SA4503. The uptake was blocked by SA4503 treatment. In the
      rat brain, only a small portion of metabolites (6.6% of brain radioactivity) was
      detected at 30 min postinjection, whereas in plasma the fraction of metabolites
      amounted to 51.3% of plasma radioactivity. The kinetics of [18F]FE-SA4503 was
      measured with PET in the conscious monkey brain. High uptake values were found in
      the cortex, thalamus, cerebellum, and striatum, reaching a plateau value at 30
      min postinjection. It is concluded that [18F]FE-SA4503 showed specific binding to
      sigma receptors in three animal species.

PMID- 11835523
TI  - Urinary levels of monocyte chemoattractant protein-1 (MCP-1) and interleukin-8
      (IL-8), and renal injuries in patients with type 2 diabetic nephropathy.
AB  - We examined the correlation among the levels of urinary monocyte chemoattractant
      protein-1 (MCP-1) and interleukin-8 (IL-8), hyperglycemia, and renal injuries in
      patients with type 2 diabetic nephropathy. The levels of urinary MCP-1, IL-8,
      protein excretion, blood urea nitrogen (BUN), serum creatinine (s-Cr),
      glycohemoglobin A1c (HbA1c), and fasting plasma glucose (FPG) were measured in 24
      patients with type 2 diabetic nephropathy and 14 healthy adults as controls.
      Diabetic nephropathy was classified into three stages: stage 1 =
      normoalbuminuric, stage 2 = microalbuminuric, and stage 3 = macroalbuminuric. All
      of the patients showed normal ranges in renal function tests. Levels of urinary
      MCP-1 in all patients with diabetic nephropathy were significantly higher than
      those in healthy adults (P < 0.05). The levels of urinary MCP-1 in patients with
      diabetic nephropathy increased gradually according to the clinical stage of this
      disease. In contrast, the levels of urinary IL-8 in patients with diabetic
      nephropathy increased in stages 2 and 3. There was a significant correlation
      between the levels of urinary IL-8 and those of HbA1c. High glucose may stimulate
      MCP-1 and/or IL-8 production and their excretion into the urine independently of
      the phases or pathological lesions of this disease. It appears that IL-8
      increased in the early stage of diabetic nephropathy, and MCP-1 increased in the
      advanced stage of this disease. It was concluded that measurement of urinary MCP
      1 and IL-8 may be useful for evaluating the degree of renal injuries in patients
      with type 2 diabetic nephropathy.

PMID- 11835522
TI  - Studies of the biogenic amine transporters. VIII: identification of a novel
      partial inhibitor of dopamine uptake and dopamine transporter binding.
AB  - Using [125I]RTI-55 to label the dopamine transporter (DAT), our laboratory has
      consistently detected one binding site as well as one component of [3H]DA uptake.
      We report here the identification of a novel partial inhibitor of [3H]DA uptake
      and DAT binding (SoRI-9804). [125I]RTI-55 binding to the DAT (mouse caudate, rat
      caudate, HEK cells expressing the cloned DAT), the 5-HT transporter (rat brain),
      and [3H]DA uptake (rat caudate synaptosomes) were conducted using published
      procedures. 4-[(Diphenylmethyl)amino]-2-phenylquinazoline (SoRI-9804) was
      essentially inactive at SERT binding and resolved two DAT binding components in
      all three tissues, having high affinity (mean Ki of 465 nM) for about 40% of the
      binding sites and an essentially immeasurable Ki (> 100 microM) for the remaining
      60% of the binding sites. The [3H]DA uptake experiments indicated that about 50%
      of uptake was SoRI-9804-sensitive. Saturation binding experiments showed that
      SoRI-9804 competitively inhibited [125I]RTI-55 binding to the SoRI-9804-sensitive
      binding component. To determine if the two binding sites discriminated by SoRI
      9804 were regulated by the MAP kinase pathway, rat caudate synaptosomes were
      incubated in the absence or presence of 10 microM of PD98059, which inhibits
      activation of the MAP kinase pathway. The results indicated that inhibition of
      MAPK/ERK kinase decreased the total B(max) of the DAT by 90%. Treatment with
      PD98059 increased the proportion of the SoRI-9804-sensitive binding component
      from 68-80% of the total B(max). The PD98059 experiments suggest that inhibition
      of MAP kinase cannot explain the differential interaction of SoRI-9804 with the
      DAT. Viewed collectively, the present results indicate that SoRI-9804
      discriminates two components of the DA transporter. Further studies will be
      needed to determine the underlying mechanism of this effect and if partial
      inhibition of DA uptake results in any unique behavioral effects.

PMID- 11835524
TI  - NIST physical standards for DNA-based medical testing.
AB  - As DNA and RNA become major targets for clinical laboratory analysis, benchmark
      reagents will play an increasingly important role in standardization. Reliable
      national and international nucleic acid standards promote automation and third
      party reimbursement for clinical testing. Furthermore, nucleic acid standards
      provide materials for quality assurance and quality control (QA/QC), and
      proficiency testing. Standard methods and training initially evolved from
      consensus guidelines endorsed by professional societies and governmental
      agencies. The National Institute of Standards and Technology (NIST), a
      nonregulatory agency of the U.S. Department of Commerce, develops and certifies
      physical and chemical standards in support of national commerce, manufacturing,
      and science. In its role supporting U.S. science and industry, the NIST responds
      to specific standards needs, most recently for medically and biologically
      important analytes. Broad-based consensus developed through interdisciplinary
      NIST workshops initiated development of NIST-certified DNA standards. Such
      materials serve the diagnostic community and help manufacturers benchmark a
      variety of DNA diagnostic testing platforms. Here we summarize the NIST
      experience and programs for development of national standards for DNA-based
      medical diagnostic testing.

PMID- 11835526
TI  - Rapid screening assay of congenital adrenal hyperplasia by measuring 17 alpha
      hydroxyprogesterone with high-performance liquid chromatography/electrospray
      ionization tandem mass spectrometry from dried blood spots.
AB  - A rapid, simple, and specific method was developed for the diagnosis of
      congenital adrenal hyperplasia (CAH) from dried blood spots on newborn screening
      cards based on high-performance liquid chromatography/electrospray ionization
      tandem mass spectrometry (HPLC/ESI-MS/MS). The usefulness of 17 alpha
      hydroxyprogesterone (17 OH-P) determination on dried filter-paper blood samples
      from patients with CAH caused by 21-hydroxylase deficiency was evaluated. The
      LC/MS/MS detection of 17 OH-P was rapid, <4 min. The intra- and interday accuracy
      and precision of the method were <7%. Our procedure maintained good linearities
      (R(2) > 0.992) and recovery rate (>83%). We used this new method to directly
      determine the 17 OH-P levels in dried blood specimens from abnormal children of
      various ages, with a detection limit of 20 ng/ml (approximately 240 pg), to avoid
      the time-consuming derivatization steps required by the gas-chromatography/mass
      spectrometry (GC/MS) method. Four dried filter-paper blood samples of CAH
      patients (three girls and one boy, 1-14 years old) were all quantified in an
      LC/MS/MS study and revealed high 17 OH-P levels (>90 ng/ml). After treatment, all
      of the elevated 17 OH-P levels either decreased or disappeared. Compared with CAH
      patients, 17 OH-P was nearly undetectable (<20 ng/ml) in the normal infants by
      LC/MS/MS. This LC/MS/MS assay is not only useful for both diagnosis and
      monitoring of treatment of CAH in all other age groups, it also can be used as a
      screening test for CAH infants. In this study, we provided the first data on 17
      OH-P in dried blood specimens affected with CAH using HPLC/ESI-MS/MS.

PMID- 11835525
TI  - Increased sialylation of polymeric lambda-IgA1 in patients with IgA nephropathy.
AB  - The mechanism of mesangial IgA deposition is poorly understood in IgA nephropathy
      (IgAN). Abnormal glycosylation of carbohydrate moieties in the hinge region of
      the IgA molecule has recently attracted much attention. In this report, we
      studied galactosylation and sialylation profiles in kappa- and lambda-IgA1 from
      patients with IgAN. Total serum IgA1 was isolated from patients with IgAN or
      healthy controls by jacalin-affinity chromatography. Six fractions of molecular
      weight (MW) 50-1,000 kDa were separated by fast protein liquid chromatography
      (FPLC). Four lectin-binding assays were used to study the sialylation and the
      presence of terminal galactose or N-acetylgalactosamine (GalNAc) in the O-linked
      carbohydrate moieties of kappa- or lambda-IgA1. Maackia amurensis agglutinin
      (MAA) and Sambucus nigra agglutinin (SNA) lectin recognize alpha(2,3)- and
      alpha(2,6)-linked sialic acid, respectively. Peanut agglutinin (PNA) and Helix
      aspersa (HA) lectin recognize terminal galactose and GalNAc, respectively.
      Reduced HA was demonstrated in macromolecular kappa or lambda-IgA1 (300-825 kDa)
      isolated from patients with IgAN (P < 0.05 compared with healthy controls).
      Lambda- but not kappa-IgA1 from patients with IgAN bound less to PNA (P < 0.05).
      The alpha(2,3)-linked sialic acid content in lambda- but not kappa-IgA1 of MW 150
      610 kDa from patients was higher than that of controls (P < 0.005). The
      alpha(2,6)-linked sialic acid content in lambda-IgA1 (300-825 kDa) and kappa-IgA1
      (150-610 kDa) from patients was also higher than that of controls. This unusual
      glycosylation and sialylation pattern of the lambda-IgA1 may have important
      implications for the pathogenesis of IgAN, as both the masking effect of sialic
      acid on galactose and the reduced galactosylation will hinder the clearance of
      macromolecular lambda-IgA1 by asialoglycoprotein receptor of hepatocytes. The
      negative charge from sialic acid may also favor mesangial deposition of
      macromolecular lambda-IgA1 in IgAN.

PMID- 11835527
TI  - Reference value of presenile human hematocrit and geographical factors.
AB  - The aim of this study was to provide a scientific basis for a unified standard of
      the reference value of healthy presenile human hematocrit in China. We studied
      the relationship between the reference values of healthy presenile human
      hematocrit, tested according to Wintrobe's laws, and five geographical factors.
      It was found that altitude is the most important factor affecting the reference
      value of the hematocrit. As the altitude gradually increases, the reference value
      of the hematocrit also increases. The relationship is quite significant. By using
      the method of stepwise regression analysis, two multivariate regression equations
      were deduced: Y1 = 39.7 + 0.00328X1 + 0.00169X2 + 0.00117X5 +/- 2.3, Y2 = 38.8 +
      0.00275X1 + 0.000578X2 -0.00298X4 +/- 2.2 In these equations, Y1 is the reference
      value of presenile men's hematocrit (%); Y2 is the reference value of presenile
      women's hematocrit (%); X1 is altitude (m); X2 is the average annual hours of
      sunshine (h); X4 is the average annual temperature (degrees C), and X5 is the
      average annual precipitation (mm). If the geographical index values in a
      particular area in China are known, the reference value of presenile human
      hematocrit in this area can be calculated approximately by means of the
      regression equations.

PMID- 11835528
TI  - Quantification of antigen-reactive T cells by a modified ELISPOT assay based on
      freshly isolated blood dendritic cells.
AB  - The enzyme-linked immunospot (ELISPOT) assay has become a widely employed method
      for quantification of antigen-reactive T lymphocytes. In recent years, various
      types of antigen-presenting cells (APCs) have been tested as stimulator cells in
      ELISPOT protocols to achieve a highly sensitive and rapid assay which is not
      impaired by a marked nonspecific cytokine release. However, the currently
      available APCs still have disadvantages, such as significant background
      reactivities, limited sensitivity, and time-consuming preparation procedures.
      Recently, we succeeded in defining a novel subpopulation of circulating dendritic
      cells (DCs) that can easily be prepared from human blood. These M-DC8+ DCs proved
      to be very effective in the induction of antigen-specific T cell responses. In
      the present study we provide evidence that M-DC8+ DCs are particularly well
      suited as APCs for the detection of antigen-specific CD8+ T cells after challenge
      with viral or tumor peptides in ELISPOT assays. In addition, protein-loaded M
      DC8+ DCs proved to be quite efficient in the presentation of MHC class II-bound
      peptides, thus allowing the determination of frequencies of antigen-reactive CD4+
      T cells. The use of M-DC8+ DCs as stimulator cells can improve the ELISPOT assay
      by combining high sensitivity, rapidity, and low background reactivity.

PMID- 11835529
TI  - Biological variability of thyroid autoantibodies (anti-TPO and anti-Tg) in
      clinically and biochemically stable patients with autoimmune thyroid disease.
AB  - The biological variation of anti-TPO and anti-Tg autoantibodies was studied in 17
      clinically and biochemically stable female patients with autoimmune thyroid
      disease (AITD), at regular monthly intervals over a period of 6 consecutive
      months. The mean and standard deviation (SD), within-subject coefficient of
      variation (CV), between-subject CV, index of individuality, reliability
      coefficient, and critical differences were as follows: for anti-TPO 238 (197)
      U/ml, 9.2%, 81.4%, 0.11, 0.96, and 27.6%; and for anti-Tg 1,785 (3,170) U/ml,
      6.9%, 174%, 0.04, 0.99, and 22.3%. The data indicate a low within-subject CV, and
      a high between-subject CV that is particularly pronounced for anti-Tg. The high
      individuality of both autoantibodies indicates that an isolated result compared
      to conventional population-based reference intervals is of very little value for
      diagnosis. Furthermore, the near to 1 reliability coefficient for both
      autoantibodies correctly classifies the patient with respect to his or her
      homeostatic mean antibody concentration in a 6-month period of clinical and
      biochemical stability of thyroid disease. Imprecision goals for anti-TPO and anti
      Tg antibodies are attainable with current methodology.

PMID- 11835530
TI  - Cytokine serum levels in patients with chronic HCV infection.
AB  - The pathogenic role of immune-mediated mechanisms in chronic hepatitis C virus
      (HCV) infection has not yet been elucidated. In this study, we report different
      cytokine expression profiles from hemodialysis (HD) and non-HD HCV (+) patients.
      IL-1beta, IL-2, IL-4, IL-6, TNF-alpha, and TGF-beta1 serum levels, and liver
      biochemical parameters were determined in 85 individuals (41 HD patients and 44
      non-HD patients). Screening for HCV RNA and anti-HCV antibodies was performed
      using qualitative and quantitative reverse transcription polymerase chain
      reaction (RT-PCR), and standardized enzyme-linked immunosorbent assay (ELISA) and
      recombinant immunoblot assay (RIBA) methods, respectively. IL-4 and IL-1beta
      demonstrated decreased serum levels in non-HD HCV carriers compared with healthy
      controls. Both T helper (Th) 1 and Th2 lymphocytes were highly associated with
      chronic HCV infection, as indicated by the increased IL-2, IL-4, and IL-6
      cytokine circulating levels in all chronic active hepatitis (CAH) patients
      examined. An enhanced Th2 response (IL-4 and IL-6) coupled with increased TNF
      alpha and IL-1beta serum levels was reported in HD HCV (-) patients. In
      conclusion, our data show that a virus-induced Th2 and IL-1beta immunosuppression
      is an early event in HCV-related chronicity. Long-term HD specifically exerts a
      chronic effect on IL-6, IL-1beta, and TNF-alpha serum circulating levels.
      Irrespective of the HD status, HCV viremia, and liver biochemistry parameters,
      both Th1 and Th2 responses are highly associated with chronic HCV infection.

PMID- 11835531
TI  - Multiplex polymerase chain reaction: a practical approach.
AB  - Considerable time and effort can be saved by simultaneously amplifying multiple
      sequences in a single reaction, a process referred to as multiplex polymerase
      chain reaction (PCR). Multiplex PCR requires that primers lead to amplification
      of unique regions of DNA, both in individual pairs and in combinations of many
      primers, under a single set of reaction conditions. In addition, methods must be
      available for the analysis of each individual amplification product from the
      mixture of all the products. Multiplex PCR is becoming a rapid and convenient
      screening assay in both the clinical and the research laboratory. The development
      of an efficient multiplex PCR usually requires strategic planning and multiple
      attempts to optimize reaction conditions. For a successful multiplex PCR assay,
      the relative concentration of the primers, concentration of the PCR buffer,
      balance between the magnesium chloride and deoxynucleotide concentrations,
      cycling temperatures, and amount of template DNA and Taq DNA polymerase are
      important. An optimal combination of annealing temperature and buffer
      concentration is essential in multiplex PCR to obtain highly specific
      amplification products. Magnesium chloride concentration needs only to be
      proportional to the amount of dNTP, while adjusting primer concentration for each
      target sequence is also essential. The list of various factors that can influence
      the reaction is by no means complete. Optimization of the parameters discussed in
      the present review should provide a practical approach toward resolving the
      common problems encountered in multiplex PCR (such as spurious amplification
      products, uneven or no amplification of some target sequences, and difficulties
      in reproducing some results). Thorough evaluation and validation of new multiplex
      PCR procedures is essential. The sensitivity and specificity must be thoroughly
      evaluated using standardized purified nucleic acids. Where available, full use
      should be made of external and internal quality controls, which must be
      rigorously applied. As the number of microbial agents detectable by PCR
      increases, it will become highly desirable for practical purposes to achieve
      simultaneous detection of multiple agents that cause similar or identical
      clinical syndromes and/or share similar epidemiological features.

PMID- 11835532
TI  - Comparison of non-diglyceride- and diglyceride-based assays for pancreatic lipase
      activity.
AB  - Pancreatic lipase is produced and stored in pancreatic acinar cells, and is
      normally secreted into the duct system. In disorders that cause pancreatic
      damage, pancreatic lipase enters the circulation, and serum lipase activity
      becomes useful in the diagnosis and evaluation of pancreatitis. During the last
      decade, many lipase assays have used the Imamura method, in which a series of
      enzymatic reactions utilizing a diglyceride substrate leads to the formation of a
      colorimetrically detected product. Historically, this method has been prone to
      significant interference from various substances, including glycerol itself. In
      the light of these limitations, we evaluated an automated enzymatic rate assay
      that uses a non-diglyceride-based, pancreatic lipase-specific substrate.
      Precision, linearity, and potential interference were assessed, and when compared
      to the Imamura method, the non-diglyceride-based assay exhibited a slope of
      0.475, y-intercept of 15.89, r-value of 0.9516, and S(y,x) of 12.96. Similar
      results were also observed when the two assays were compared using samples with
      markedly elevated creatinine levels. Between-day coefficients of variance (CVs)
      ranged from 5.0% to 5.5%, which compared well with the diglyceride-based method,
      and linearity spanned a range of 3-156 U/L. Evaluation of over 2,000 patient
      results collected during a 6-month period suggested that the manufacturer's upper
      reference limit of 51 U/L may be too conservative. No significant interference
      was identified with bilirubin, triglyceride, or glycerol itself, and significant
      interference from hemoglobin was observed only at concentrations of 116 mg/dL or
      greater. As a result, the non-diglyceride-based method provides an acceptable
      alternative for the routine laboratory measurement of lipase activity.

PMID- 11835533
TI  - Simple genotype analysis of the Asp299Gly polymorphism of the Toll-like receptor
      4 gene that is associated with lipopolysaccharide hyporesponsiveness.
AB  - A nonsynonymous single nucleotide polymorphism (Asp299Gly) in the Toll-like
      receptor-4 (TLR-4) gene affects the responsiveness to lipopolysaccharide in
      humans. To analyze this important polymorphism more efficiently, we developed a
      simple polymerase chain reaction (PCR) restriction length fragment polymorphism
      (RFLP) assay and examined the Asp299Gly allele frequency in a Japanese
      population. The PCR primer was designed with 1- or 2-bp mismatches, creating the
      recognition sequence for restriction enzyme BsaBI or BstXI, allowing RFLP
      analysis of the digested products. Genotyping was carried out with this assay for
      275 DNA specimens from 107 healthy volunteers and 168 patients with various
      diseases, including ulcerative colitis (n = 86). The Asp299Gly allele of the TLR
      4 gene was not detected in any of the specimens, suggesting that it is very rare
      in Japanese.

PMID- 11835535
TI  - The accessory nerve clarified.

PMID- 11835534
TI  - Variability in molecular typing of Coxsackie A viruses by RFLP analysis and
      sequencing.
AB  - The aim of the present study was to develop an assay capable of classifying the
      Coxsackie A virus (CAV) prototype strains on the basis of restriction fragment
      length polymorphism (RFLP) analysis of 5'-UTR-derived reverse transcription
      polymerase chain reaction (RT-PCR) amplicons, and to determine how these data
      could be used for typing wild-type CAV isolates. Moreover, sequencing of the
      amplified genomic fragments of the clinical isolates, and comparison with all the
      published sequences of the respective genomic region of enterovirus reference and
      wild-type strains were attempted for typing of the isolates. Twenty-four
      prototype CAV strains from the 23 currently recognized serotypes were studied;
      most of them were successfully differentiated with the aid of four restriction
      endonucleases: HaeIII, HpaII, DdeI, and StyI. It was not possible to
      differentiate between CAV5, 7, and 16, or between CAV15 and 18 in this way, but
      the members of each of these two groups were satisfactorily differentiated with
      the aid of single-strand conformational polymorphism (SSCP) analysis of their RT
      PCR amplicons. Fifteen clinical isolates, 13 of them of known CAV serotype, were
      also studied with the same four endonucleases and the results were compared with
      the data obtained from the RFLP analysis of the reference strains. The
      experimental results showed that only two clinical samples of previously known
      identity had an identical restriction pattern with the respective prototype
      strains. The sequences of the amplicons of the clinical isolates had the greatest
      percentage of alignment with enterovirus strains of a different serotype,
      indicating variability in the 5'-UTR and the inability to use the whole sequence
      of the amplicons for typing CAVs. The significance of the findings in relation to
      the possible usefulness of the RFLP-based method is discussed.

PMID- 11835536
TI  - Thomas Willis 1621-1675.

PMID- 11835537
TI  - Anatomical evidence for the absence of a morphologically distinct cranial root of
      the accessory nerve in man.
AB  - The accessory nerve is conventionally described as having a cranial and spinal
      root. According to standard descriptions the cranial root (or part) is formed by
      rootlets that emerge from the medulla between the olive and the inferior
      cerebellar peduncle. These rootlets are considered to join the spinal root,
      travel with it briefly, then separate within the jugular foramen to become part
      of the vagus nerve. In 15 fresh specimens we exposed the posterior cranial fossa
      with a coronal cut through the foramen magnum and explored the course of each
      posterior medullary rootlet (PMR) arising from within the retro-olivary groove.
      We chose the caudal end of the olive as the landmark for the caudal end of the
      medulla. In all specimens every PMR that did not contribute to the
      glossopharyngeal nerve joined the vagus nerve at the jugular foramen. The
      distance between the caudal limit of the olive and the origin of the most caudal
      PMR that contributed to the vagus nerve ranged from 1-21 mm (mean = 8.8 mm). All
      rootlets that joined the accessory nerve arose caudal to the olive. The distance
      from the caudal limit of the olive and the most rostral accessory rootlet ranged
      from 1-15 mm (mean = 5.4 mm). We were unable to demonstrate any connection
      between the accessory and vagus nerves within the jugular foramen. Our findings
      indicate that the accessory nerve has no cranial root; it consists only of the
      structure hitherto referred to as its spinal root.

PMID- 11835538
TI  - Patterns of connections between the musculocutaneous and median nerves in the
      axilla and arm.
AB  - Variations in connections between the musculocutaneous and median nerves in the
      arm are not as uncommon as was once thought. This opinion led us to perform a
      study in 138 cadavers (66 male, 72 female). These variations were seen in 64
      cadavers (46.4%), 9 bilaterally and 55 unilaterally (26 right and 29 left); in
      total, therefore, variations were observed in 73 out of 276 arms (26.4%), 42 male
      and 31 female. No statistically significant differences by gender and side were
      observed. We classify the variations in three main patterns: Pattern 1, fusion of
      both nerves (14 arms, 19.2%); Pattern 2, presence of one supplementary branch
      between both nerves (53 arms, 72.6%); and Pattern 3, two branches (5 arms, 6.8%).
      Pattern 2 was further subdivided into a sub-group 2a when a single root from the
      musculocutaneous nerve contributed to the connection (51 arms, 69.9%), and 2b
      when there were two roots from the musculocutaneous nerve (2 arms, 2.7%). A
      combination of Patterns 1 and 2a was observed in one case (1.4%). Further
      variations are described, published classification systems are reviewed and a
      meta-analysis of previous results is presented. An overall incidence of 33% of
      variant arms was observed. Of these variant arms, Pattern 1 represented 13.1%,
      Pattern 2 represented 75.4%, and Pattern 3, 8.5%, similar to our figures.

PMID- 11835539
TI  - Quantitative morphology of full thickness rotator cuff tears.
AB  - The occurrence of full thickness rotator cuff tears (RCTs) at time of death, the
      size and distribution of those tears among the tendons of the rotator cuff, and
      the anterior to posterior and medial to lateral dimensions of the RCTs were
      determined. A subset of 57 shoulders from a group of 414 were found to have full
      thickness rotator cuff tears. The three-dimensional coordinates of specific bony
      landmarks and points defining the circumference of the RCT were digitized using a
      Flock of Birds DC electromagnetic tracking device. Bony landmarks were used to
      determine the separation between adjacent tendons of the rotator cuff. Points
      describing the circumference of the RCT were used to calculate the area of the
      tear. The majority of tears occurred in the supraspinatus tendon alone (25), or
      in both the supraspinatus and infraspinatus tendons (22). The areas of the RCTs
      ranged from 0.07 cm(2) to 19.17 cm(2) with an average of 4.43 cm(2). The mean
      anterior to posterior length was 1.95 cm. The mean medial to lateral length was
      1.98 cm.

PMID- 11835540
TI  - Identification of unilateral elbow-joint position is impaired by Parkinson's
      disease.
AB  - We have compared the ability of patients with idiopathic Parkinson's disease (PD)
      with that of control subjects to identify unilateral elbow-joint position, in the
      absence of direct vision of the arm, by visual reference to a graduated angular
      scale, placed beside the elbow, across a range of test angles of 90-108 degrees.
      The positioning of the subject's elbow was achieved under either passive (subject
      relaxed, Experiment 1) or active (subject contracting, Experiment 2) conditions.
      PD patients' performance (while on L-dopa medication) with the elbows on the
      sides of "worse" and "better" motor signs was compared with that of controls
      with, respectively, the left and right elbows. In both experiments, (a) both the
      individual, overall mean unsigned (with respect to direction) error averaged
      across all test angles (accuracy), and the SD about this mean (precision), were
      significantly larger on each side among PD patients than among controls, and (b)
      the subjective ranges of values employed by PD patients were substantially
      compressed, on average, by comparison with those of controls. Within-group
      analyses revealed that (a) among control subjects, but not among PD subjects,
      individual, overall mean unsigned errors, on each side, averaged across test
      angles, were significantly smaller under active than under passive conditions,
      and (b) the subjective ranges employed by PD patients, but not by controls, under
      active conditions significantly exceeded those under passive conditions. We
      conclude that these results are generally consistent with the notion that PD
      impairs unilateral elbow-joint position sense.

PMID- 11835541
TI  - Abnormal digastric muscle with unilateral quadrification of the anterior belly.
AB  - During dissection of the submental region we observed that the anterior belly of
      the left digastric muscle had four separate insertions. These muscle bands united
      in a common tendon as they continued with the posterior belly. This is an
      anatomical variation in the mylohyoid digastric muscle group in the floor of the
      mouth. When an asymmetry in the floor of the mouth is detected during diagnostic
      procedures, such as radiologic studies, anomalies of the anterior belly of the
      digastric muscle should be considered besides other reasons of asymmetry.
      Additionally, possible occurrence of such anomalies should be remembered during
      surgical procedures involving the submental region. This unique variation has not
      been reported in the literature.

PMID- 11835542
TI  - The nerve supply of the human auricle.
AB  - Knowledge of the innervation of the outer ear is crucial for surgery in this
      region. The aim of this study was to describe the system of the auricular nerve
      supply. On 14 ears of seven cadavers the complete course of the nerve supply was
      exposed and categorized. A heterogeneous distribution of two cranial branchial
      nerves and two somatic cervical nerves was found. At the lateral as well as the
      medial surface the great auricular nerve prevails. No region with triple
      innervation was found.

PMID- 11835543
TI  - Importance of dissection in learning anatomy: personal dissection versus peer
      teaching.
AB  - Two studies or approaches to time savings in teaching gross anatomy were
      implemented and tested. Personal dissection vs. peer teaching of the upper and
      lower extremities revealed subtle effects of dissection on examination
      performance. Although peer teaching was generally successful, students preferred
      to dissect for themselves, lacking confidence in being taught by other students.
      ANOVA and multiple range tests carried out on the examination means indicated no
      difference between each student's scores on upper and lower extremity questions.
      However, subtle effects were reflected in significant differences (P < 0.05) in
      both ratio (upper%/lower%) and difference (upper%-lower%) between each student's
      percent scores on upper extremity and lower extremity questions, indicating
      enhanced performance on the extremity dissected. Students dissecting both
      extremities were intermediate in both ratio and difference, and not significantly
      different from either the "upper" or "lower" extremity groups. A questionnaire
      indicated that students who dissected only one extremity would have preferred to
      have dissected both extremities, and, contrary to overall examination
      performance, disagreed that they had learned both extremities at a satisfactory
      level. Although documenting adequate learning with time savings, the results are
      consistent with the contention that hands-on dissection enhances learning and
      confidence in the subject matter, because examination performance as well as
      personal satisfaction was enhanced on the extremity that was dissected.

PMID- 11835544
TI  - Clinical anatomy as the basis for clinical examination: development and
      evaluation of an Introduction to Clinical Examination in a problem-oriented
      medical curriculum.
AB  - Clinical anatomy is usually defined as anatomy applied to patient care. The
      question is asked whether students of a new horizontally and vertically
      integrated medical curriculum recognize the subject as the basis for clinical
      examination. A clinical anatomy practicum was developed in the special activity,
      "Introduction to Clinical Medicine," held in the second year of the Pretoria
      medical curriculum. The practicum was conducted on a station basis to
      anatomically prepare the student for the inspection, palpation, percussion, and
      auscultation of the cardiovascular, respiratory, abdominal, and urogenital
      systems. A total of 23 stations consisting of eight cardiovascular, seven
      respiratory, and eight abdominal/urogenital stations were designed. Standardized
      patients, cadavers, skeletons, prosected specimens, x-rays, computed tomography
      (CT) scans, magnetic resonance imaging (MRI), multimedia programs, and clinical
      case studies were used as resources. A Likert-type questionnaire was used for
      student evaluation of the practicum. Most students realized the importance of
      surface anatomy for a family physician. More than two-thirds thought the
      practicum improved their understanding of the anatomical basis for clinical
      examination. The minority of students were stimulated to do further reading on
      clinical examination. The students' response to their ability to integrate the
      clinical examination with the radiological anatomy was average. Most students
      were continuously aware of the appropriateness of the practicum for their future
      career. We conclude that medical students recognize the importance of anatomy as
      the basis for clinical examination when exposed to an appropriate integrated
      presentation format.

PMID- 11835545
TI  - Evaluation of practical sessions in clinical anatomy: a strategy for educational
      improvement.
AB  - We have evaluated the students' response to the practical teaching sessions in
      Clinical Anatomy in our Medical School using an action-research method. The aim
      was to identify problems and to introduce changes that might improve both the
      program and the performance of the teaching staff. At the end of each section of
      the program, each student completed a "target type" questionnaire with eight
      different components. As each one quarter of the whole class had its own teacher,
      we used an analysis of variance to evaluate the target questions in the various
      sections of the program, and the performance of the four teachers. This research
      method gave us feedback on the students' responses while the program was in
      progress. The results emphasize the importance of action-research in assessing
      and improving a developing program in a basic discipline of the medical
      curriculum.

PMID- 11835546
TI  - Evaluation of the Clinical Anatomy Program in the Medical School of Porto by two
      cohorts of students.
AB  - The discipline of Clinical Anatomy, as introduced in the Medical School of Porto
      in academic year 1995/96, involved major changes in the way we teach anatomy to
      medical students, by adopting a clinically oriented approach. A questionnaire was
      designed to evaluate the opinion of second-year medical students enrolled in the
      program concerning main aspects of the discipline in two consecutive years; 84%
      of the students returned the questionnaire in 1996/97, and 70% in 1997/98.
      Students were asked about the level of their approval of the organization of the
      discipline, the role of the teaching staff, lectures, practical sessions,
      educational media, and continuous and summative assessments. For items replicated
      in both academic years, the means of the sum of scores in each year were compared
      (Student's t-distribution). Whenever a significant difference was found, changes
      in individual items were tested (chi-square distribution). The evaluation of the
      discipline in each of the two years was highly favorable for most of the
      parameters analyzed.

PMID- 11835547
TI  - Anomalous relationship of the spinal accessory nerve to the internal jugular
      vein.
AB  - A patient with an early cancer of the tongue and undergoing a staging neck
      dissection was noted to have an anomalous relationship of the internal jugular
      vein and spinal accessory nerve. At the upper end of the dissection (level II,
      Memorial Sloan-Kettering classification), the internal jugular vein was observed
      to divide above and reconstitute below the spinal accessory nerve. Although
      apparently not previously described in the literature, this finding may be
      encountered by other surgeons who operate in this area, and it is important that
      these anatomical variations are borne in mind to prevent inadvertent injury.

PMID- 11835548
TI  - An additional renal vein.
AB  - A routine cadaveric dissection in an adult male revealed the emergence of two
      renal veins at the hilum of the right kidney that presented two separate openings
      in the inferior vena cava (IVC), one above the other. At the hilum the segmental
      branches of the right renal artery were sandwiched between the two veins. An
      additional venous tributary was present posterior to the right renal pelvis. A
      single renal vein emerged at the hilum of the left kidney. The various
      tributaries observed on the right and left sides were measured. The possible
      developmental basis for this variation suggests the persistence of the embryonic
      pattern observed in the 22 mm embryo.

PMID- 11835549
TI  - The sternalis muscle.

PMID- 11835552
TI  - Ernest L. Eliel: a life of purpose, determination, and integrity.
AB  - A concise biography of Ernest L. Eliel is presented. The highlights of Eliel's
      scientific achievements are described, beginning with his Ph.D. thesis research
      performed under the supervision of Professor Harold Snyder (University of
      Illinois) and continuing as a faculty member at Notre Dame (synthesis of
      nonracemic C(6)H(5)CHDCH(3); kinetic method of conformational analysis;
      equilibrium and NMR methods of conformational analysis); and at the University of
      North Carolina (conformational analysis of heterocyclic compounds;
      enantioselective synthesis). Eliel's professional career as a teacher, textbook
      author, and major figure in the American Chemical Society are discussed. His
      philosophies of life, science, and chemistry are described by a series of
      poignant quotations.

PMID- 11835553
TI  - Role of the heteroatom on stereoselectivity in the complex metal hydride
      reduction of six-membered cyclic ketones.
AB  - The role of the heteroatom on the stereochemistry and the relative rate for the
      complex metal hydride reduction of heteracyclohexanones and methoxy substituted
      cyclohexanones is explained by the difference in the nonbonding two electron
      stabilization between the incipient sigma* bond and the anti periplanar allylic
      sigma(i) bonds which were perturbed by the through space and/or through bond
      interaction with the remote heteroatom. A significant directive effect of the 2
      axial hydroxyl group appears in the reduction of cyclohexanone with
      representative complex metal hydrides, while the 3 axial hydroxyl group exhibits
      a steric hindrance. The distance between the carbonyl carbon and the hydroxyl
      group which interacts with the hydride reagent is mainly responsible for such a
      difference. The key point of the extremely high directive effect appeared in the
      Na[B(OAc)(3)H] reduction for both 2 and 3 axial hydroxycyclohexanone is the
      formation of Na[B(OAc)(2)(OR)H], which is far more reactive than the parent
      hydride, by exchanging the acetate ion with the alkoxide.

PMID- 11835554
TI  - Structure, conformation, and mechanism in the membrane transport of alkali metal
      ions by ionophoric antibiotics.
AB  - Recent progress in studies of the mechanism of transport of alkali metal ions by
      ionophoric antibiotics and the structures of alkali metal salts of the ionophores
      monensin and narasin is reviewed. The structures obtained from 2D NMR experiments
      in solution provide considerable insights into the mechanisms of transport.

PMID- 11835555
TI  - Stereochemical terminology and its discontents.
AB  - Scrutiny of the purported misuse of some current stereochemical terms shows that
      obsolescence and faulty syntax may be less of a problem than previously assumed.
      Furthermore, changes in stereochemical terminology over time are not always due
      to obsolescence or to novel developments in chemical technology; for example,
      technical developments played no role whatsoever in the semantic transmutations
      over time of the terms "diastereomer" and "pseudoasymmetry." Finally, definitions
      of many stereochemical terms acquire meaning only within a given context and
      therefore cannot always be easily formulated. A prime example is the definition
      of "chirality," the concept at the heart of stereochemistry and, not
      coincidentally, the name of the journal in which this essay appears in print.

PMID- 11835556
TI  - Asymmetric induction under confinement.
AB  - Confinement may efficiently condition the stereochemical outcome of a reaction
      through space constriction and molecular close contact. This article briefly
      reviews recent approaches of supramolecular chemistry to achieve chiral
      confinement. Crystallization is not always possible and the use of chiral
      crystals or clathrates lacks generality. The construction of solid supramolecular
      assemblies circumvents some of the problems of the crystal chemistry. In this
      regard, molecular imprinting of polymeric matrices with orifices mimicking the
      transition state of an enantioselective process is a very young, promising
      technique. Zeolites provide porous, rigid environments to host molecules without
      the need of lucky crystallizations, yet zeolites are not chiral per se and must
      be chirally modified. Besides, the limited dimension of their pores restricts the
      size of the guest molecules. Despite these problems, useful asymmetric
      photochemical reactions have been performed on zeolites. Finally, the formation
      of pillared lamellar structures, from inorganic salts of tetravalent transition
      metals covalently grafted with organic chains, is considered. The adequate
      selection of functionality and chirality of the organic pillars would afford
      custom-made, highly porous, 3D hybrid organo-inorganic scaffolds. However, the
      production of asymmetric processes within these layered materials still remains
      to be seen.

PMID- 11835557
TI  - Preparation of (R) and (S) alpha methyldopa from a chiral hydantoin containing
      the alpha phenylethyl group.
AB  - Chiral hydantoin (S)-1 was prepared in good yield from phenyl isocyanate and N
      [(S)-alpha-phenylethyl]glycinate, (S)-3. Enolate (S)-1-Li was methylated in high
      yield and good diastereoselectivity. In contrast, a second alkylation reaction of
      methylated enolate (S)-4-Li proceeded with essentially no diastereoselectivity.
      Nevertheless, dialkylated hydantoins, (S,S)-7 and (S,R)-7, could be readily
      separated by flash chromatography and subsequent hydrolysis of either derivative
      afforded the desired (S)-L-alpha-methyldopa or (R)-D-alpha-methyldopa in good
      yield.

PMID- 11835558
TI  - Electronic effects on the regio- and enantioselectivity of the asymmetric
      aminohydroxylation of O-substituted 4-hydroxy-2-butenoates.
AB  - Regio- and enantioselectivity in the asymmetric aminohydroxylation (AA) reaction
      of O-substituted 4-hydroxy-2-butenoates as well as the mechanism of the reaction
      were studied. When the electronic properties of the phenyl group in a substrate
      were altered by using different substituents, two conflicting trends were
      observed: The O-benzoyl substrates showed greater regio- and enantioselectivity
      when an electron-donating substituent was attached at the C-4 position of the
      phenyl group, while the O-benzyl substrates exhibited better regio- and
      enantioselectivity with an electron-withdrawing substituent at the C-4 position
      of the phenyl moiety. Thus, these results have disclosed hitherto unknown
      remarkable electronic effects in the AA reaction. Detailed analysis of possible
      electronic interactions in the chiral catalyst-substrate complex has revealed the
      importance of dipolar aromatic-aromatic interactions between the aromatic
      substituent of the substrate and the nitrogen heteroaromatic moiety of the chiral
      ligand for effective regiocontrol as well as enantioface selection in the AA
      reaction. A plausible model of the key intermediate in the AA reaction of O
      substituted 4-hydroxy-2-butenoates is proposed.

PMID- 11835559
TI  - Regioselective and stereoselective cleavage of cis-4-methyl-2-vinyl-l,3-dioxane
      by alkyllithiums.
AB  - The reaction of alkyllithiums with cis-4-methyl-2-vinyl-1,3-dioxane proceeds in
      virtually quantitative yield via a formal S(N)2' ring opening that proceeds in a
      regioselective manner to give preferential cleavage of the C(2)-O(l) bond remote
      from the 4-methyl substituent, affording the E-enol ether as the major
      stereoisomer. A two-step mechanism, involving addition of the alkyllithium
      followed by syn-elimination of lithium alkoxide, is suggested to account for the
      stereochemical outcome.

PMID- 11835560
TI  - Highly enantioselective asymmetric autocatalysis of 2-alkenyl- and 2-vinyl-5
      pyrimidyl alkanols with significant amplification of enantiomeric excess.
AB  - 2-Alkenyl- and 2-vinyl-5-pyrimidyl alkanols are highly enantioselective
      asymmetric autocatalysts with significant amplification of enantiomeric excess in
      the enantioselective addition of diisopropylzinc to 2-alkenyl- and 2
      vinylpyrimidine-5-carbaldehydes. Consecutive asymmetric autocatalysis starting
      from 7% ee increases the ee of pyrimidyl alkanol up to 99% without the need for
      any other chiral auxillary.

PMID- 11835561
TI  - Enantioselective carbon-hydrogen insertion is an effective and efficient
      methodology for the synthesis of (R)-(-)-baclofen.
AB  - A highly enantioselective methodology for the synthesis of the GABA(B) receptor
      agonist (R)-(-)-baclofen is described. This synthesis begins with p
      chlorophenethyl alcohol and involves a catalytic carbon-hydrogen insertion
      reaction of a chiral dirhodium(II) carboxamidate with the corresponding
      diazoacetate (81% yield, 95% ee). Subsequent steps convert the intermediate gamma
      lactone to (R)- (-)-baclofen in a 60% overall yield. The amount of catalyst
      required for the C-H insertion transformation is only 0.5 mol%.

PMID- 11835562
TI  - Computational and experimental studies of di- and tetrasubstituted
      calix[4]arenes.
AB  - Calixarenes are molecular bowls or baskets that have been demonstrated to serve
      as hosts for cations, anions, and neutral molecules. The central cavity and
      scaffolding of various functionalities on the upper and lower rims establishes
      this class of compounds as extremely important in supramolecular chemistry
      studies. In earlier studies, calixsugars (molecules that have sugar molecules
      appended to the upper rim of the calix) were prepared. Among the potential
      advantages of these molecules are increased water solubility and enhanced
      possibilities that these chiral attachments can promote enantiomeric selection.
      Computational studies, however, have indicated that the chosen calixsugars had
      significantly encumbered upper rims, suggesting that host-guest associations
      would be limited. In an attempt to understand those factors responsible for the
      favored conformations of calixsugars, a number of 5,17-disubstituted and
      tetrasubstituted calix[4]arenes were prepared and studied experimentally as well
      as by molecular mechanics conformational searching techniques.

PMID- 11835563
TI  - Diene chirality and cotton effects of nonhomoannular cisoid conjugated dienes:
      circular dichroism and crystal structure of a steroidal 19-nor-1(10),9(11)-diene
      derived from Westphalen's diol diacetate.
AB  - Nonhomoannular cisoid conjugated dienes exhibit negative lowest energy pi-->pi*
      Cotton effects when they have P diene chirality and positive CEs when they have M
      diene chirality. We investigated this relationship further with a variety of such
      dienes by MM2 conformational energy-minimization calculations and by an X-ray
      crystal structure of a steroidal 19 nor 1(10),9(11) diene. CEs are stronger when
      each double bond of the diene is endocyclic in a different ring and weaker when
      only one of the double bonds is endocyclic or when neither double bond is
      endocyclic. They are also stronger when axial allylic and homoallylic
      substituents with CH/pi interactions are present that exert consignate chirality
      contributions.

PMID- 11835564
TI  - 1H, (13)C, and (15)N NMR stereochemical study of cis-fused 7a(8a)-methyl and 6
      phenyl octa(hexa)hydrocyclopenta[d][1,3]oxazines and [3,1]benzoxazines.
AB  - Four 7a-methyl octa(or hexa)hydrocyclopenta[d][1,3]oxazines, five 8a-methyl
      octa(or hexa)hydro[3,1]benzoxazines, two 6-phenyl hexahydro[3,1]benzoxazinones,
      and 8a-methyl hexahydro[1,3]benzoxazinone, all cis-fused, were prepared and their
      stereostructures studied by various one- and two-dimensional (1)H, (13)C, and
      (15)N NMR spectroscopic methods. In solution, the cyclopentane-fused 2-oxo
      derivatives and the 1,3-benzoxazinone were found to attain exclusively the N-in/O
      in conformation, whereas the 6-phenyl 2-oxo/thioxo derivatives were found to be
      present predominantly in the N-out conformation. The C-2 unsubstituted and the 2
      oxo/thioxo 7a/8a-methyl derivatives were all present in solution as a rapidly
      interconverting equilibrium of the N-in and N-out conformations. The C-2 methyl
      derivatives were each found to be interconvertable mixtures of epimers (at C-2)
      with the N-in conformer predominating for one epimer and the N-out conformer
      predominating for the other, with both predominating conformers having the C-2
      methyl group equatorially orientated. The substituent on the nitrogen (H or Me)
      was found to be always predominantly equatorial with respect to the heteroring,
      except for the epimeric 2-methyl derivatives with N-out conformations where
      steric constraints and the generalized anomeric effect resulted in the axial
      orientation of the C-2 methyl being favored.

PMID- 11835565
TI  - Alkylating agents from sugars: synthesis of chlorambucil derivatives carried by
      chiral glycosyl glycerols derived from D-glucosamine.
AB  - Chlorambucilamide derivatives involving chiral glycosyl glycerols derived from D
      glucosamine were synthesized in good yield by coupling the chlorambucil moiety to
      the amino group of omega-amino-(omega-1)-hydroxyalkyl 2-acylamino-4,6-O
      benzylidene-2-deoxy-beta-D-glucopyranosides, and subsequent hydrolysis of the
      benzylidene group. The starting material was easily available from 2-acetamido-2
      deoxy-D-glucose. The bonding of 2,3,4,6-tetra-O-pivaloyl-beta-D
      galactopyranosylamine to chlorambucil by formation of an amide function is also
      described.

PMID- 11835566
TI  - An NMR investigation of the conformational equilibria of 2-(2'
      pyridyl)ethylphosphonic acid in several solvents.
AB  - Vicinal proton-proton NMR couplings have been used to investigate whether the
      position of conformational equilibria is determined by intramolecular N-H
      hydrogen bonding for 2-(2'-pyridyl)ethylphosphonic acid 1 in its various possible
      ionization states in water, methanol, ethanol, and dimethyl sulfoxide (DMSO).
      With 1 in the form of its monoanion and dianion, the trans is favored, with the
      dianion being more trans than the monoanion for a given solvent, probably as the
      result of steric effects, possibly enhanced by repulsive electrostatic effects
      between the negatively charged phosphonic group and the lone pair on the pyridine
      nitrogen. For 1 and its conjugate acid, the gauche amounts, respectively, to 43%
      and 45% in water, 66% and 51% in methanol, 66% and 64% in ethanol, and 29% and
      49% in DMSO. For these latter two species, electrostatic, steric, and hydrogen
      bonding-effects are all likely to play a role in determining the conformational
      equilibria.

PMID- 11835567
TI  - Atropisomerism as a probe of restrictions to motion above and below the glass
      transition temperature of Polymers.
AB  - This short review and interpretation of work conducted in the authors' laboratory
      concerns the use of atropisomeric 1,1'-binaphthyl derivatives to gain information
      about the glassy properties of polymers. Bridged binaphthyls appended with
      oligophenyl paddles are found to yield a series of probes whose racemization
      kinetics reveal new kinds of information concerning the basis of the time scale
      and length scale for the restrictions to motion and the heterogeneity of the
      polymeric glassy state. Because the time scale of the racemization is slower than
      all other glass probes used previously, new kinds of information were gained for
      the first time below the glass transition temperature.

PMID- 11835568
TI  - Determination of the absolute configuration of a key tricyclic component of a
      novel vasopressin receptor antagonist by use of vibrational circular dichroism.
AB  - We present the results of a study using vibrational circular dichroism (VCD) for
      (+)-1, which furnished an unambiguous determination of its absolute configuration
      as S. The most abundant conformation of (+)-1 in CDCl(3) solution was also
      established.

PMID- 11835569
TI  - Molecular mechanics (MM4) force field development for phosphine and its alkyl
      derivatives.
AB  - Based on the experimental structures and vibrational spectra of eight
      alkylphosphines, as well as ten ab initio calculated (MP2/6-31+g*) structures and
      five potential energy profiles, the MM4 force field has been extended to include
      this important functional group. The results are comparable to experimental
      values for phosphorus-containing compounds. The addition of various cross-terms
      significantly improved the MM4 calculated structures relative to its predecessor,
      MM3. The overall root mean square error in moments of inertia have been reduced
      from 1.65% in MM3 to 0.26% in MM4. MM4 was also successful in reducing the
      previously impressive root mean square error in vibrational frequencies from 35
      cm(-1) to 31 cm(-1) for the eight compounds studied.

PMID- 11835570
TI  - Four conformers characterized in allyl nitrite.
AB  - Allyl nitrite, O=NOCH(2)CH=CH(2), can exist in conformations which include syn
      (S) and anti (A) configurations of O=N-O-C, anti or gauche (G) configurations of
      N-O-C-C, and syn or skew (Sk) configurations of O-C-C=C. Four of them have been
      observed and characterized by their microwave spectra and quantum chemical
      calculations to have AGSk' (0.0 kcal/mol), AGSk (0.2(2) kcal/mol), SASk (0.2(2)
      kcal/mol), and SAS (0.9(2) kcal/mol) configurations about the three successive
      dihedral angles. All four are observed in microwave studies of the vapor at 300
      and 200 K and the first three are seen in pulsed-jet beams. The SAS form
      apparently relaxes to the SASk conformer during expansion in the pulsed-jet.
      Quantum chemical calculations reveal that the two possible conformers with anti
      anti configurations of the O=N-O-C-C fragment, AAS and AASk, are transition
      states, unstable configurations, or of marginal stability, consistent with
      structures observed in this and other previously studied alkyl nitrites. The
      remaining four possible conformers are predicted to have relative energies within
      1 kcal/mol of the observed conformers but were not observed experimentally.

PMID- 11835571
TI  - Stereospecific cleavage of carbon-phosphorus bonds: stereochemical course of the
      phosphinoyl curtius (Harger) reaction.
AB  - The homochiral phosphinic azides (R,R)-1 and (S,S)-1 were prepared in
      enantiomerically pure form by resolution of diastereomeric phosphinamides derived
      from (S)-l-phenylethylamine and (R)-phenylglycine. Irradiation of the azides in
      methanol induced a photo-Curtius rearrangement to phosphonamidates in which the
      stereogenic carbon unit migrated to a nitrogen atom. Hydrolysis of the
      phosphonamidates produced 1-phenylethylamine, which was 99.0% e.e. and of the
      same configuration as the carbon unit in the starting azide (99.0% retention).

PMID- 11835572
TI  - Hydrobenzoin-based rigid chiral polymer.
AB  - We prepared a rigid, chiral polymer (1) from optically active hydrobenzoin-based
      subunits. Nonracemic monomer units 6 and 8 were prepared by asymmetric
      dihydroxylation (AD) methodology and polymerization was carried out under
      Sonagashira coupling conditions. Polymer 1 was obtained in good yield with a
      molecular weight M(n) = 5,100 (PDI = 2.3). Modeling suggests that polymer 1 could
      form a stable helical mainchain conformation in solution or the solid state. The
      chiroptical data of the polymer and a low-molecular weight model compound (9) are
      compared.

PMID- 11835574
TI  - Golgi matrix protein gene, Golga3/Mea2, rearranged and re-expressed in pachytene
      spermatocytes restores spermatogenesis in the mouse.
AB  - In a transgenic mouse, Golga3/Mea2 gene (human homolog: GOLGA3/golgin-160) was
      disrupted by a translocation at the site of the transgene integration. Exons 8-24
      of the disrupted gene remained intact and formed a fusion gene (DeltaMea2) with
      the antisense strand of E. coli-derived transgene by means of a cryptic splice
      signal in there. The protein product of DeltaMea2, virtually a form truncated to
      2/3 of the normal size, localized to Golgi apparatus of pachytene spermatocytes
      and round spermatids. DeltaMea2 expression was specific to the testis, but varied
      among separate seminiferous tubules. It also showed variation among homozygous
      individuals from 0.5 to 4.3% of the wild type (wt) level. At the lowest levels,
      neither spermatids nor spermatozoa were present in the homozygous testes, but
      when the expression of DeltaMea2 increased to 4.3% of the wt level, high sperm
      production was restored and a sporadic (1/22) fertile homozygous male was
      obtained. The earliest apoptotic degeneration of pachytene spermatocytes
      evidenced at 17 dpp in homozygous testes in some discrete seminiferous tubules
      was preceded by DeltaMea2 expression in a variegated fashion at 16 dpp. These
      results consistently indicated that in homozygous testes, the pachytene
      spermatocytes which failed to express DeltaMea2 may undergo apoptotic
      degeneration. Golga3/Mea2, and DeltaMea2 in homozygotes, in a certain excessive
      amount may be important for survival of pachytene spermatocytes in the mouse.

PMID- 11835573
TI  - Trophectoderm-specific expression of the X-linked Bex1/Rex3 gene in
      preimplantation stage mouse embryos.
AB  - The Bex1/Rex3 gene was recently identified as an X-linked gene that is
      differentially expressed between parthenogenetic and normal fertilized,
      preimplantation stage mouse embryos. The Bex1/Rex3 gene appears to be expressed
      preferentially from the maternal X chromosome in blastocysts, but from either X
      chromosome in later stage embryonic tissues and adult tissues. To investigate
      whether differential expression of the Bex1/Rex3 gene between normal and
      parthenogenetic blastocyst stage embryos reflects genomic imprinting at the
      Bex1/Rex3 locus itself, or instead is the result of preferential inactivation of
      the paternal X chromosome or differences in timing of cellular differentiation,
      we examined in detail the expression pattern of the Bex1/Rex3 mRNA in normal
      preimplantation stage embryos, and compared its expression between androgenetic,
      gynogenetic, and normal fertilized embryos. Expression data reveal that the
      Bex1/Rex3 gene is initially transcribed at the 2-cell stage, transiently induced
      at the 8-cell stage, and then increases in expression again at the blastocyst
      stage. Very little expression is observed in isolated inner cell masses,
      indicating selective expression in the trophectoderm. Comparisons of Bex1/Rex3
      mRNA expression between male and female androgenetic and control embryos and
      gynogenetic embros failed to reveal any significant difference in expression
      between the different classes of embryos at the 8-cell stage, or the expanding
      blastocyst stage (121 hr post-hCG). At the late blastocyst stage (141 hr post
      hCG), expression was significantly lower in XY control embryos as compared with
      XX controls. Bex1/Rex3 mRNA expression did not differ between XX and XY
      androgenones at the blastocyst stage or between gynogenones and XX control
      embryos. Thus, the Bex1/Rex3 gene does not appear to be regulated directly by
      genomic imprinting during the preimplantation period, just as it is not regulated
      by imprinting at later stages. Apparent differences in gene expression may arise
      through the effects of trophectoderm-specific expression coupled with differences
      in timing of trophectoderm differentiation between the different classes of
      embryos and effects of preferential paternal X chromosome inactivation (XCI).

PMID- 11835575
TI  - Transgenic pigs expressing human decay-accelerating factor regulated by porcine
      MCP gene promoter.
AB  - Porcine membrane cofactor protein (pMCP) is abundantly expressed throughout the
      body with particularly strong expression on the vascular endothelia. Previous
      studies demonstrated that the promoter of the pMCP gene induced efficient
      expression of a human complement regulatory protein, decay-accelerating factor
      (DAF; CD55), in transgenic mice. In the present study, we tried to produce
      transgenic pigs with two hybrid genes, 0.9/hDAF and 5.4/hDAF, which were composed
      of human DAF (hDAF) gene regulated under pMCP promoters of different lengths (0.9
      and 5.4 kb). Five live founder transgenic pigs were obtained only with the
      0.9/hDAF construct. Although, four founder pigs transmitted the transgene to the
      second generation, the transmission rates varied among founders. We examined the
      expression of hDAF in tissues of descendants of two lines (Dm1 and Dm4). Human
      DAF specific RNAs were confirmed by an RT-PCR analysis in all organs examined.
      Levels of hDAF protein in the organs from the descendants of Dm1 line were higher
      than those in the corresponding human organs as determined by enzyme-linked
      immunosorbent assay. Immunohistochemical studies showed that the tissue
      distribution of hDAF in the descendants of both lines was similar to that of
      endogenous pMCP. The expression level of hDAF on the vascular endothelial cells
      in Dm1 line was twice that on the corresponding human cells. We tested whether
      proinflammatory cytokines upregulate an efficiency of pMCP promoter on hDAF
      expression in transgenic pigs. Although the expression of hDAF on the human
      endothelial cells increased with a combination of cytokines, tumor necrosis
      factor alpha and interferon-gamma, no cytokine-induced upregulation was seen in
      the cells of transgenic pigs. The endothelial cells from transgenic pigs
      exhibited high resistance to the human serum-mediated cytolysis.

PMID- 11835576
TI  - Hyaluronan is an abundant constituent of the extracellular matrix of Xenopus
      embryos.
AB  - The spatiotemporal distribution of hyaluronan (HA), a major constituent of the
      vertebrate extracellular matrix, was analyzed during early embryonic development
      of Xenopus laevis. This polysaccharide is abundantly present in ventricular
      structures such as the blastocoel, the archenteron as well as later on in the
      hepatic cavity, the brain ventricles and the developing heart. At the blastula
      stage, HA was detected in the extracellular matrix of the ecto- and mesodermal
      primordia. Shortly before gastrulation, it becomes enriched at the basal site of
      the superficial cell layer of the ectoderm. During gastrulation, enhanced
      synthesis of HA takes place in the involuting marginal zone, shortly before
      invagination starts, hence, resulting in a torus-like deposition in the deep
      layer of the equatorial mesodermal primordium. After gastrulation, HA appears to
      accumulate within the extracellular matrix demarcating the primary germ layers.
      During tailbud stages, it is found highly enriched in many mesodermal
      derivatives, e.g., in mesenchyme, the heart, precordal cartilage and the lung
      primordia. Furthermore, extracellular matrix of the ventral mesodermal cell layer
      in the trunk region and the immediate proximity of blood vessels contain high
      amounts of HA.

PMID- 11835577
TI  - Effects of follicular size of cytoplast donor on the efficiency of cloning in
      cattle.
AB  - In cattle, oocytes obtained from follicles smaller than 3 mm in diameter can
      undergo maturation in vitro, progressing to MII and undergoing fertilization, but
      are developmentally incompetent. Cytoplasts were prepared from in vitro matured
      oocytes aspirated from small (1-3 mm) or large (6-12 mm) follicles and fused to
      serum starved mural granulosa cells. Following activation, reconstructed embryos
      were cultured for 7 days and classified G1 to G4, before being processed for
      nuclei counting or transferred to synchronized recipients. Oocytes from small
      follicles had lower rates of polar body extrusion (59.6 vs. 69%; 731/1230 vs.
      608/857) and fusion (71.4 vs. 78.8%; 360/497 vs. 364/465; P < 0.06). There were
      no differences in total rate of blastocysts development (60 vs. 59.8%; small vs.
      large), or any grade classification. A significant interaction was detected
      between follicle size and embryo grade with G3 embryos from small follicles
      having a greater cell number. Developmental competence of G1 and G2 embryos did
      not differ at day 27 (48 vs. 46%; 16/33 vs. 17/37; small vs. large). Although
      there were no differences in fetal size between the two groups, differences in
      allantois length (53 vs. 86 mm; small vs. large; P < 0.002) and allantois width
      (9.5 vs. 13 mm; small vs. large; P < 0.06) were seen. No differences in survival
      to term (2/13 in each group) were observed. These results indicate that
      cytoplasts from follicles of 1-3 and 6-12 mm in diameter are equally
      developmentally competent when used in a nuclear transfer procedure.

PMID- 11835578
TI  - Essential role of ZP molecules in tubal transport of embryos in mice.
AB  - Our understandings of the molecular and cellular mechanisms underlying tubal
      transport of embryos are poor. This study describes the essential role of the
      molecules on the zona pellucida (ZP) in the tubal transport of mouse embryos. The
      bovine and porcine embryos that were interspecifically transferred to the mouse
      oviduct were selectively retained in the oviduct and rarely transported to the
      uterus. Antiserum ZP3-9 against synthetic peptides that are specific for mouse
      ZP3, significantly interfered with tubal transport of the treated embryos. The
      treatment of mouse embryos with antiserum ZP2-20 against the synthetic peptides,
      deduced from the sequences that are conserved in the structure of ZP2 from mouse
      and human, also inhibited their tubal transport. Among various proteolytic and
      glycosidic enzymes, treatments with trypsin and beta-glucosidase prior to
      transfer to the oviduct, significantly interfered with the tubal transport of the
      enzyme-treated mouse embryos. We hypothesize that species-specific epitopes on
      the ZP may be recognized by the oviductal cilia and/or the epithelial cells of
      ducts for tubal transport.

PMID- 11835579
TI  - DNA topoisomerase II distribution in mouse preimplantation embryos.
AB  - DNA topoisomerase II (topo II) is an essential enzyme that mediates a variety of
      chromosome activities including DNA replication, transcription, recombination,
      and chromosome condensation and segregation. Isoform-specific anti-topo II
      antibodies were used to determine the distribution of topo II alpha and beta in
      mouse gametes and embryos. Immunoblot analysis with two anti-topo IIalpha
      antibodies revealed that a 170 kDa topo IIalpha band was present in ovary and
      testis. Mature sperm exhibited an 89 kDa band only, which may be a degradation
      product of topo IIalpha. Immunoblots probed with a monoclonal antibody that
      recognizes both isoforms, showed bands at 170 and 180 kDa, which correspond to
      topo IIalpha and beta, respectively. An additional 100 kDa band was also present
      in ovary and testis. Mature sperm did not exhibit staining with this antibody. We
      also localized topo II in mouse gametes and embryos up to the blastocyst stage
      using immunofluorescence microscopy. While both isoforms were found in nuclei and
      nucleoli of germinal vesicle oocytes, topo IIalpha localized to metaphase
      chromosomes during meiosis, and only to nucleoli during embryonic interphase.
      Topo IIbeta was absent from chromosomes of metaphase II oocytes, but localized to
      embryonic interphase nuclei. Both full-length isoforms were absent from sperm,
      indicating topo II is stored maternally. These results identify topo II as an
      important component of mouse oocyte and embryonic chromatin, and suggest its
      involvement in oocyte maturation and preimplantation embryonic development. The
      different immunofluorescent staining patterns indicate topo IIalpha and beta may
      serve different roles during the embryonic cell cycle.

PMID- 11835580
TI  - DNA topoisomerase II is essential for preimplantation mouse development.
AB  - Topoisomerase II (topo II) is an essential enzyme that alters DNA topology. This
      activity is important for a variety of chromosome functions including DNA
      replication, transcription, recombination, and chromosome condensation and
      segregation. Previously we localized topo II in mouse gametes and preimplantation
      embryos using isoform-specific antibodies demonstrating the presence of the
      enzyme in oocytes and embryos, but not sperm. To probe functions of topo II
      during preimplantation development, we treated mouse zygotes with 100 nM
      teniposide, and assessed embryo morphology and DNA replication. Teniposide
      blocked cleavage in 69% embryos; the remainder cleaved once but had abnormal
      nuclei. Teniposide-treated embryos were devoid of topo II immunofluorescence.
      Teniposide also prevented DNA replication, implicating topo II in this process.
      Embryos treated with a 2 hr pulse of teniposide recovered and developed to the
      blastocyst stage, indicating 100 nM teniposide did not induce apoptosis. To more
      specifically analyze topo IIalpha function, we treated zygotes with topo IIalpha
      targeted antisense oligodeoxynucleotides. Most zygotes arrested at the 2-cell
      stage while controls developed into blastocysts indicating topo IIalpha is
      essential for preimplantation development. The absence of topo IIalpha, but not
      beta immunofluorescence in antisense-treated embryos confirms the specificity and
      impact of the treatment. In addition, topo IIalpha is newly synthesized at the 2
      cell stage. These results establish an essential function for topo II in mouse
      preimplantation embryonic development.

PMID- 11835581
TI  - Role of cholesterol in germ-line development of Caenorhabditis elegans.
AB  - We investigated the effects of cholesterol starvation on Caenorhabditis elegans
      development at both embryonic and post-embryonic stages by examining brood size,
      embryonic lethality, growth rate, and worm size. The brood sizes of worms grown
      without cholesterol were substantially reduced in subsequent generations as
      compared to the control group with cholesterol: 13, 33, and 39% at the first, the
      second, and the third generation, respectively. The growth rate was also reduced
      by 20%-26%. Worms became adults after 120-130 hr incubation at 20 degrees C.
      Embryonic lethality was detected in the range of 1.6%-2.9% as compared to 0.8% of
      the control group. The percent development from an embryo to an adult was lowered
      by an average of 10%. Further analyses of germ line development to understand the
      reduction of brood size revealed that both germ line proliferation and
      differentiation were affected, and the most striking effect was seen in
      oogenesis. Defective oogenesis resulted in endomitotic oocytes (Emo, 22% at F1,
      26% at F2, and 30% at F3). Thus, cholesterol appears to be required for all
      developmental stages of C. elegans.

PMID- 11835582
TI  - A estradiol-17beta receptor in the reproductive system of the female of Octopus
      vulgaris: characterization and immunolocalization.
AB  - In this study, for the first time we have identified an estradiol-17beta receptor
      (ER) in the reproductive system of the female of Octopus vulgaris. Scatchard
      analysis revealed that one binding component with high affinity and low capacity
      for the ligand was present in the cytosol, but not in the nuclear extract of the
      ovary and the oviduct. A steroid specificity competition assay showed that 3H
      estradiol-17beta binding activity showed a preference for estradiol-17beta. DNA
      cellulose chromatography confirmed the presence of one 3H-estradiol-17beta
      binding component. By using antibodies anti ER (578-595), we have localized by
      Western blotting one band of about 70 kDa. ER immunoreactivity has been localized
      in the nuclei of the follicle cells of the ovary, in the nuclei of the epithelium
      lining the proximal portion of the oviduct and in the nuclei, and in the
      cytoplasm of the inner region of the oviducal gland and in the cytoplasm of the
      outer region of the oviducal gland. These data, taken together, provide evidence
      that in Octopus vulgaris the ER has biochemical and immunohistochemical
      characteristics resembling those of ER in vertebrates.

PMID- 11835583
TI  - Quantitative analysis of flagellar movement in hyperactivated and acrosome
      reacted golden hamster spermatozoa.
AB  - Caudal epididymal spermatozoa of golden hamsters were incubated in capacitation
      medium. Their movement patterns changed as they became hyperactivated and
      underwent the acrosome reaction. To understand the basic mechanism by which
      changes in movement pattern are brought about, digital image analysis was carried
      out on the flagellar movements recorded with a video system. The degree of
      flagellar bending increased with incubation time, especially in the proximal
      midpiece. The hyperactivated spermatozoa had remarkably asymmetrical flagellar
      waves of large amplitude because either the bends in the same direction as the
      hook of the head (referred as the "pro-hook bend") or the bends in the opposite
      direction to the hook of the head (referred as the "anti-hook bend") extremely
      increased their curvature; whereas, the acrosome-reacted spermatozoa had
      relatively symmetrical flagellar waves of large amplitude because both the pro-
      and anti-hook bends remarkably increased their curvature. Beat frequency
      significantly decreased while wavelength of flagellar waves increased after
      hyperactivation and further after the acrosome reaction. These results suggest
      that both extreme pro- and anti-hook bends are essential in the acrosome-reacted
      spermatozoa even though beat frequency decreased markedly.

PMID- 11835584
TI  - Oral antioxidants counteract the negative effects of female aging on oocyte
      quantity and quality in the mouse.
AB  - This study aims to compare the effect of early and late onset administration of
      oral antioxidants on number and quality of oocytes retrieved from aged mice after
      exogenous ovarian stimulation. Control hybrid females were fed a standard diet
      supplemented or not supplemented with pharmacological doses of vitamins C and E
      either from the first day of weaning or from the age of 32 weeks until they were
      autopsied at the age 40-42, 50-52, or 57-62 weeks after exogenous ovarian
      stimulation. Analysis of chromosomal distribution, DNA organization and cellular
      morphology was performed in ovulated cumulus-enclosed and -free oocytes, ovarian
      non-germinal vesicle oocytes enclosed by or free of mucous cumulus cells and in
      vitro-matured ovarian germinal-vesicle oocytes. Both early and late onset
      administration of oral antioxidants counteracted the negative effects of female
      aging on number of ovarian oocytes and total percentage of oocytes retrieved from
      oviducts and ovaries exhibiting a normal distribution of chromosomes in the
      metaphase-II plate and/or morphological traits of apoptosis. Although both early
      and late onset administration of oral antioxidants can counteract the negative
      effects of female aging on number and quality of oocytes, transference of these
      results to human beings should be made with caution because of the potential side
      effects of high doses of vitamins on reproductive function as well as many other
      undesirable systemic disorders.

PMID- 11835585
TI  - Stage of the estrous cycle at the time of pregnant mare's serum gonadotropin
      injection affects the quality of ovulated oocytes in the mouse.
AB  - The present study aims to analyze the effect of the stage of the estrous cycle at
      the time of pregnant mare's serum gonadotropin (PMSG) injection on number and
      quality of mouse oocytes retrieved from oviducts after exogenous ovarian
      stimulation. Cellular and morphological traits of ovulated oocytes from hybrid
      (C57Bl/6JIco female X CBA/JIco male) female mice of 12, 40-42, 50-52 or 57-62
      weeks of age were analyzed. Superovulation was induced by a priming injection of
      PMSG at different stages of the estrous cycle followed after a 48-hr interval by
      human chrorionic gonadotropin. Injection of PMSG at diestrus-1 was associated
      with: (1) increased percentage of cumulus-free oocytes; (2) raised total
      percentage of oocytes without polar body; (3) increased total percentage of
      oocytes with intracytoplasmic mitochondrial aggregates; (4) decreased percentage
      of oocytes with a normal distribution of chromosomes in the metaphase II plate;
      and (5) raised percentage of oocytes with chromosome scattering when compared to
      injection at estrus, diestrus-2, and proestrus stage. On the contrary, estrus
      females displayed the highest percentage of oocytes with a normal distribution of
      chromosomes in the metaphase II plate and the lowest percentage of oocytes
      denuded of cumulus cells, without polar body, with intracytoplasmic mitochondrial
      aggregates and/or with chromosome scattering. These data suggest that
      administration of gonadotropins in mice should be synchronized with the innate
      estrous cycle of females to optimize the quality of oocytes collected from
      oviducts.

PMID- 11835587
TI  - Minireview: Functions of the cumulus oophorus during oocyte maturation,
      ovulation, and fertilization.

PMID- 11835586
TI  - Ubiquitin-dependent sperm quality control mechanism recognizes spermatozoa with
      DNA defects as revealed by dual ubiquitin-TUNEL assay.
AB  - Defective mammalian spermatozoa become ubiquitinated during epididymal passage, a
      mechanism that may mark the abnormal spermatozoa for proteolytic destruction
      (Sutovsky et al., 2001a: J Cell Sci 114:1665-1675). It is not known how such
      spermatozoa are recognized by the epididymal ubiquitination pathway and whether
      there is a selection against certain types of sperm defects. We examined the
      relationship between sperm ubiqutination, lifelong sperm morphology and sperm DNA
      defects using a single chanel, ubiquitin-activated flow cytometric assay, and a
      dual, ubiquitin-TUNEL assay. Semen samples from nine service sires of good-to
      average fertility were screened. A positive correlation was found between sperm
      ubiquitination and the average frequency of morphological semen abnormalities
      from field evaluations performed throughout the reproductive life of individual
      sires. Sample correlation coefficients were r=0.65 for primary (head and tail)
      and r=0.60 for total semen abnormalities in the single channel assay. In a dual
      assay, we found a high, positive correlation (r=0.93) between the ubiquitin
      positive sperm and the TUNEL positive sperm. Substantial correlations (r=0.47
      0.64) were observed when the measurements from these two respective assays were
      compared for individual sires. While anti-ubiquitin antibodies recognized most of
      the TUNEL-positive sperm cells, the TUNEL-positive spermatozoa represented only a
      subset (approximately 20-40%) of all ubiquitin-positive cells. It appears that
      the ubiquitin-dependent sperm quality control, residing in the epididymal
      epithelium, has the ability to detect spermatozoa with apoptotic or necrotic DNA,
      while spermatozoa with defects other than DNA fragmentation are also recognized
      and ubiquitinated.

PMID- 11835588
TI  - Daily assessment of coping in patients with gastrointestinal cancer.
AB  - Ninety-five patients with gastrointestinal (GI) cancer participated in a study
      concerning stressful events, coping and emotional well-being. Participants were
      either potentially cured (n=62) after radical surgery or non-cured (n=33). For a
      period of 1 week, close to being informed about their diagnosis, they performed
      daily recordings of stressful events, the distress occasioned by these events and
      their perception of control over them, coping, worry and happiness/sadness.
      Anxiety and depression were assessed by a single retrospective assessment at the
      end of the week (Hospital Anxiety and Depression (HAD) scale). The most commonly
      recorded stressful events were 'Somatic aspects' and 'Everyday concerns'.
      'Somatic aspects', 'Social aspects' and 'Other consequences of the disease' were
      rated as most bothersome. Patients perceived that they had the highest degree of
      control over 'Returning home after hospital stay', whereas 'Contact with the
      medical services' was assigned low control. The most commonly used coping
      strategies were 'Acceptance' and 'Relaxation', and the least used was 'Religion'.
      Significant positive correlations between the occurrence of stressful events and
      the use of coping strategies were demonstrated between 'Somatic Aspects' and
      'Acceptance'/'Direct Action', and between 'Social Aspects' and 'Seeking Social
      Support'. Daily assessment of stress-coping relationships represents a promising
      approach to the understanding of adaptation among cancer patients.

PMID- 11835589
TI  - Predictors of depressive symptomatology of geriatric patients with lung cancer-a
      longitudinal analysis.
AB  - BACKGROUND: Lung cancer is a major health problem throughout the world. It is the
      leading cause of cancer-related death in men and women in the USA, with a 5-year
      survival rate of only 14%. It has been hypothesized that variables such as
      physical and social functioning, cancer-related symptomatology, comorbid
      conditions, cell type, and treatment are valid predictors of the psychological
      response to a diagnosis of lung cancer. METHODS: As part of a larger longitudinal
      study, 211 patients, 65 years of age or older, with an incident diagnosis of lung
      cancer, were recruited from 23 sites within a midwestern state. Repeated measures
      analysis of variance techniques were used to analyse how age, gender, comorbid
      conditions, stage of disease, cell type, as well as the time-dependent variables
      symptoms, physical functioning, social functioning, and treatment predict
      depressive symptomatology at four assessments over the first year following
      diagnosis. RESULTS: Social functioning (p<0.0001), symptoms severity (p<0.0001)
      and radiation treatment (p=0.017) were significant predictors of depressive
      symptomatology, with more symptoms and more restricted social functioning
      generally corresponding to higher levels of depressive symptomatology. Patients
      who had not received radiation treatment were more depressed than those who had
      received treatment at least 40 days prior to the interview. CONCLUSIONS: At a
      clinical level of patient care, these findings mandate early identification of
      psychosocial difficulties experienced, an individualized symptom management plan
      and the application of other interventions, such as information giving,
      reassurance and referral to other resources.

PMID- 11835590
TI  - Sensory and affective dimensions of advanced cancer pain.
AB  - The present study was designed to explore the extent to which advanced cancer
      pain is explicable in terms of both physical pain intensity and affect. Most
      notably, it expanded on previous findings by more clearly elucidating the
      relationship between several discrete emotional states and the total experience
      of cancer pain. One hundred and eleven patients with cancer pain attending a Pain
      and Symptom Control Clinic were studied. Visual Analogue Scales (VASs) were used
      to quantify overall pain intensity and the accompanying affect. Then,
      correlations were calculated to evaluate the relationships both between and
      within these two variables. Overall, the participants rated both the pain
      intensity and the negative affect associated with that pain as high. Of the
      examined affective components of pain, frustration and exhaustion were found to
      be the most significant. In addition, some gender differences were identified in
      terms of frustration, anger, fear, exhaustion, helplessness, and hopelessness.

PMID- 11835591
TI  - Communication in the cancer 'bad news' consultation: patient perceptions and
      psychological adjustment.
AB  - The purpose of this study was to explore relationships between breast cancer
      survivors' experiences during the diagnostic consultation and their subsequent
      long-term psychological adjustment. Sixty women (M age=53 years) who had been
      diagnosed with local or regional breast cancer (Stage 0-IIIA) an average of 28
      months prior were interviewed by telephone. Measures included: Cancer Diagnostic
      Interview Scale, Anxiety subscale of the Hospital Anxiety and Depression Scale,
      Posttraumatic Stress Disorder Checklist - Civilian Version, Center for
      Epidemiologic Studies Depression Scale, and ad hoc items regarding memory for,
      and satisfaction with, the diagnostic consultation. After controlling for
      demographic and clinical variables, the three CDIS subscales accounted for 12% of
      the variance in women's PCL-C scores (F change=3.46, p<0.05). The CDIS-Caring
      subscale was a significant predictor in the 'best-fit' regression model for each
      of the three indices of long-term distress (all B's>-0.23, p<0.05). In contrast,
      the CDIS-Competence subscale was not a significant predictor in any of the 'best
      fit' models. Additionally, women's satisfaction with physician behavior during
      the diagnostic consultation was unrelated to all adjustment measures (r's<0.10,
      p's>0.50). Findings suggest that women's perceptions of physicians' interpersonal
      skills during the diagnostic consultation are associated with later psychological
      adjustment.

PMID- 11835592
TI  - Oncologists' reactions to cancer patients' verbal cues.
AB  - The diagnosis and treatment of cancer cause considerable psychological distress
      and morbidity. Consequently, cancer patients have high needs for informational
      and emotional support and doctors vary in their ability to recognise and address
      these needs. This study investigated patients' attempts to gain informational and
      emotional support through the use of verbal cues. The sample consisted of 298
      patients with heterogeneous cancers, seeing one of five medical and four
      radiation oncologists for the first time. Sociodemographic variables and patient
      anxiety and satisfaction ratings were obtained. Transcripts of the audiotaped
      consultations were analysed and question-asking, use of indirect cues, cue type
      (informational or emotional), content categories in which questions and cues
      occurred and doctor response (responded to or not responded to), were recorded.
      Patients asked a median of 11 questions and gave two cues per consultation,
      usually during treatment discussions. Patients gave, and doctors responded to,
      more informational than emotional cues. Patients gave significantly more
      informational cues during longer consultations. Younger and female patients gave
      more cues for emotional support and asked questions. No demographic variables
      were associated with the doctors' response to emotional and informational cues;
      however, consultations in which more informational cues were responded to were
      shorter, even when controlling for the number of cues given. Satisfaction with
      the consultation and patient anxiety were unaffected by doctors' responses to
      cues. Overall, results showed that doctors effectively identify and respond to
      the majority of informational cues; however, they are less observant of and able
      to address cues for emotional support. Cues can be addressed without lengthening
      the consultation or increasing patient anxiety.

PMID- 11835593
TI  - Multiple endocrine neoplasia type 2a (MEN2a): a call for psycho-social research.
AB  - This paper summarizes what is known about the diagnosis, treatment, and follow
      care of people with the inherited disorder multiple endocrine neoplasia type 2a
      (MEN2a). Several databases were searched throughout the year 2000, including
      MEDLINE, CINAHL, CancerLit, PsychINFO, and Dissertation Abstracts International.
      MEN2a is a complex disease involving cancer care and control by surgery, health
      maintenance, and life-long observation of gene mutation carriers. Genetic testing
      is the standard of care, prophylactic surgery is recommended during directive
      counseling, and life-long surveillance is encouraged for people with MEN2a. A
      substantial body of scientific literature describes morbidity and mortality
      outcomes of disease treatment, and the monitoring of multiple organ systems.
      Research is scant concerning the psychological consequences and social impact of
      the MEN2a diagnosis, treatment, and follow-up. Nearly all that is known from a
      psycho-social perspective comes from data in The Netherlands. Little is known of
      the psychological responses to and social consequences of genetic predisposition
      testing, prophylactic and curative surgery, and life-long surveillance. Psycho
      social research is essential to provide comprehensive care for patients and
      family members with this disorder and it is necessary to guide the development of
      risk management strategies for patients with this inherited cancer syndrome.
      Since MEN2a has been labeled a prototype for medical genetics, information on
      MEN2a patient experiences may be relevant to the care of individuals with other
      inherited cancer syndromes.

PMID- 11835594
TI  - Psychological adjustment of 'surgery-only' pediatric neuro-oncology patients: a
      retrospective analysis.
AB  - A recent increase in diagnoses of pediatric neuro-oncology tumors combined with
      recent advancements in medical treatment of such tumors has resulted in a growing
      cohort of pediatric brain tumor survivors. These survivors are at risk for short
      and long-term psychological adjustment problems. Most studies regarding these
      survivors have focused on children who have received combinations of surgery,
      radiation, and chemotherapy as medical treatment. The sub-group of pediatric
      neuro-oncology patients who receive surgery as the only form of medical treatment
      has not been closely followed for adjustment problems. In this study, data were
      retrospectively collected from semi-structured clinical interviews with 34
      'surgery-only' pediatric neuro-oncology patients who were 2 weeks to 5 years off
      medical treatment for their tumor. These data suggest that these survivors may be
      experiencing significant short and long-term mood, behavioral, and academic
      adjustment problems in comparison to national averages for children regarding
      these issues. Additional research examining the psychological adjustment process
      for surgery-only pediatric neuro-oncology patients is needed to validate these
      preliminary findings and facilitate the development of targeted interventions to
      address the identified adjustment problems.

PMID- 11835599
TI  - Shape-selective stereo processing in human object-related visual areas.
AB  - Object related areas in the human ventral stream were previously shown to be
      activated, in a shape-selective manner, by luminance, motion, and texture cues.
      We report on the preferential activation of these areas by stereo cues defining
      shape. To assess the relationship of this activation to object recognition, we
      employed a perceptual stereo effect, which profoundly affects object recognition.
      The stimuli consisted of stereo-defined line drawings of objects that either
      protruded in front of a flat background ("front"), or were sunk into the
      background ("back"). Despite the similarity in the local feature structure of the
      two conditions, object recognition was superior in the "front" compared to the
      "back" configuration. We measured both recognition rates and fMRI signal from the
      human visual cortex while subjects viewed these stimuli. The results reveal shape
      selective activation from images of objects defined purely by stereoscopic cues
      in the human ventral stream. Furthermore, they show a significant correlation
      between recognition and fMRI signal in the object-related occipito-temporal
      cortex (lateral occipital complex).

PMID- 11835600
TI  - Neural basis for sentence comprehension: grammatical and short-term memory
      components.
AB  - We monitored regional cerebral activity with BOLD fMRI while subjects were
      presented written sentences differing in their grammatical structure (subject
      relative or object-relative center-embedded clauses) and their short-term memory
      demands (short or long antecedent-gap linkages). A core region of left posterior
      superior temporal cortex was recruited during all sentence conditions in
      comparison to a pseudofont baseline, suggesting that this area plays a central
      role in sustaining comprehension that is common to all sentences. Right posterior
      superior temporal cortex was recruited during sentences with long compared to
      short antecedent-gap linkages regardless of grammatical structure, suggesting
      that this brain region supports passive short-term memory during sentence
      comprehension. Recruitment of left inferior frontal cortex was most clearly
      associated with sentences that featured both an object-relative clause and a long
      antecedent-gap linkage, suggesting that this region supports the cognitive
      resources required to maintain long-distance syntactic dependencies during the
      comprehension of grammatically complex sentences.

PMID- 11835601
TI  - Cortical sources of the early components of the visual evoked potential.
AB  - This study aimed to characterize the neural generators of the early components of
      the visual evoked potential (VEP) to isoluminant checkerboard stimuli.
      Multichannel scalp recordings, retinotopic mapping and dipole modeling techniques
      were used to estimate the locations of the cortical sources giving rise to the
      early C1, P1, and N1 components. Dipole locations were matched to anatomical
      brain regions visualized in structural magnetic resonance imaging (MRI) and to
      functional MRI (fMRI) activations elicited by the same stimuli. These converging
      methods confirmed previous reports that the C1 component (onset latency 55 msec;
      peak latency 90-92 msec) was generated in the primary visual area (striate
      cortex; area 17). The early phase of the P1 component (onset latency 72-80 msec;
      peak latency 98-110 msec) was localized to sources in dorsal extrastriate cortex
      of the middle occipital gyrus, while the late phase of the P1 component (onset
      latency 110-120 msec; peak latency 136-146 msec) was localized to ventral
      extrastriate cortex of the fusiform gyrus. Among the N1 subcomponents, the
      posterior N150 could be accounted for by the same dipolar source as the early P1,
      while the anterior N155 was localized to a deep source in the parietal lobe.
      These findings clarify the anatomical origin of these VEP components, which have
      been studied extensively in relation to visual-perceptual processes.

PMID- 11835602
TI  - Human brain oscillatory activity phase-locked to painful electrical stimulations:
      a multi-channel EEG study.
AB  - The main aims of this study were 1) a fine spatial analysis of
      electroencephalographic (EEG) oscillations after galvanic painful stimulation
      (nonpainful stimulation as a reference) and 2) a comparative evaluation of phase-
      and nonphase-locked component of these EEG oscillations. Preliminary surface
      Laplacian transformation of EEG data (31 channels) reduced head volume conductor
      effects. EEG phase values were computed by FFT analysis and the statistical
      evaluation of these values was performed by Rayleigh test (P < 0.05). About 50%
      of the EEG single trials presented statistically the same FFT phase value of the
      evoked EEG oscillations (phase-locked single trials), indicating a preponderant
      phase-locked compared to nonphase-locked component. The remaining single trials
      showed random FFT phase values (nonphase-locked single trials), indicating a
      preponderant nonphase-locked compared to phase-locked component. Compared to
      nonpainful stimulation, painful stimulation increased phase-locked theta to gamma
      band responses in the contralateral hemisphere and decreased the phase-locked
      beta band response in the ipsilateral hemisphere. Furthermore, nonphase-locked
      alpha band response decreased in the ipsilateral fronto-central area. In
      conclusion, both decreased and increased EEG oscillatory responses to galvanic
      painful stimulation would occur in parallel in different cortical regions and in
      the phase- and nonphase-locked EEG data sets. This enriches the actual debate on
      the mapping of event-related oscillatory activity of human brain.

PMID- 11835603
TI  - Neural representation of verb meaning: an fMRI study.
AB  - The neural basis for verb comprehension has proven elusive, in part because of
      the limited range of verb categories that have been assessed. In the present
      study, 16 healthy young adults were probed for the meaning associated with verbs
      of MOTION and verbs of COGNITION. We observed distinct patterns of activation for
      each verb subcategory: MOTION verbs are associated with recruitment of left
      ventral temporal-occipital cortex, bilateral prefrontal cortex and caudate,
      whereas COGNITION verbs are associated with left posterolateral temporal
      activation. These findings are consistent with the claim that the neural
      representations of verb subcategories are distinct. Although the "sensory-motor"
      hypothesis may play a role in explaining activation associated with MOTION verbs,
      the left posterolateral temporal distribution of cortical activation associated
      with COGNITION verbs cannot be easily explained by the "sensory-motor"
      hypothesis. We suggest that left posterolateral temporal activation supports
      aspects of lexical semantic processing concerned with the neural representation
      of propositional knowledge contributing to COGNITION verbs.

PMID- 11835604
TI  - Cluster analysis of activity-time series in motor learning.
AB  - Neuroimaging studies of learning focus on brain areas where the activity changes
      as a function of time. To circumvent the difficult problem of model selection, we
      used a data-driven analytic tool, cluster analysis, which extracts representative
      temporal and spatial patterns from the voxel-time series. The optimal number of
      clusters was chosen using a cross-validated likelihood method, which highlights
      the clustering pattern that generalizes best over the subjects. Data were
      acquired with PET at different time points during practice of a visuomotor task.
      The results from cluster analysis show practice-related activity in a fronto
      parieto-cerebellar network, in agreement with previous studies of motor learning.
      These voxels were separated from a group of voxels showing an unspecific time
      effect and another group of voxels, whose activation was an artifact from
      smoothing.

PMID- 11835605
TI  - Modeling of activation data in the BrainMap database: detection of outliers.
AB  - We describe a system for meta-analytical modeling of activation foci from
      functional neuroimaging studies. Our main vehicle is a set of density models in
      Talairach space capturing the distribution of activation foci in sets of
      experiments labeled by lobar anatomy. One important use of such density models is
      identification of novelty, i.e., low probability database events. We rank the
      novelty of the outliers and investigate the cause for 21 of the most novel,
      finding several outliers that are entry and transcription errors or infrequent or
      non-conforming terminology. We briefly discuss the use of atlases for outlier
      detection.

PMID- 11835606
TI  - Lie detection by functional magnetic resonance imaging.
AB  - The accurate detection of deception or lying is a challenge to experts in many
      scientific disciplines. To investigate if specific cerebral activation
      characterized feigned memory impairment, six healthy male volunteers underwent
      functional magnetic resonance imaging with a block-design paradigm while they
      performed forced-choice memory tasks involving both simulated malingering and
      under normal control conditions. Malingering that demonstrated the existence and
      involvement of a prefrontal-parietal-sub-cortical circuit with feigned memory
      impairment produced distinct patterns of neural activation. Because astute liars
      feign memory impairment successfully in testing once they understand the design
      of the measure being employed, our study represents an extremely significant
      preliminary step towards the development of valid and sensitive methods for the
      detection of deception.

PMID- 11835607
TI  - Implementation and application of a brain template for multiple volumes of
      interest.
AB  - We present a region template and a protocol for transforming that template to
      define anatomical volumes of interest (VOIs) in the human brain without operator
      intervention, based on software contained in the SPM99 package (Statistical
      Parametric Mapping, Wellcome Department of Cognitive Neurology, London, UK). We
      used an MRI of a reference brain to create an anatomical template of 41 VOIs,
      covering the entire brain, that can be spatially transformed to fit individual
      brain scans. Modified software allows for the reslicing and adaptation of the
      transformed template to any type of coregistered functional data. Individually
      defined VOIs can be added. We present an assessment of the necessary spatial
      transformations and compare results obtained for scans acquired in two different
      orientations. To evaluate the spatial transformations, 11 landmarks distributed
      throughout the brain were chosen. Euclidean distances between repeat samples at
      each landmark were averaged across all landmarks to give a mean difference of 1.3
      plus minus 1.0 mm. Average Euclidean distances between landmarks (MRI:transformed
      template) were 8.1 plus minus 3.7 mm in anterior-posterior commissure (ACPC) and
      7.6 plus minus 3.7 mm in temporal lobe (TL) orientation. In this study, we use
      [(11)C]-flumazenil-(FMZ-)PET as an example for the application of the region
      template. Thirty-four healthy volunteers were scanned, 21 in standard ACPC
      orientation, 13 in TL orientation. All had high resolution MRI and FMZ-PET. The
      average coefficient of variation (CV) of FMZ binding for cortical regions was
      0.15, comparable with CVs from manually defined VOIs. FMZ binding was
      significantly different in 6/19 anatomical areas in the control groups obtained
      in the different orientations, probably due to anisotropic voxel dimensions. This
      new template allows for the reliable and fast definition of multiple VOIs. It can
      be used for different imaging modalities and in different orientations. It is
      necessary that imaging data for groups compared are acquired in the same
      orientation.

PMID- 11835608
TI  - Nonlinear phase desynchronization in human electroencephalographic data.
AB  - Ensembles of coupled nonlinear systems represent natural candidates for the
      modeling of brain dynamics. The objective of this study is to examine the complex
      signal produced by coupled chaotic attractors, to discuss their potential
      relevance to distributed processes in the brain, and to illustrate a method of
      detecting their contribution to human EEG morphology. Two measures of quantifying
      the behavior of coupled nonlinear systems are presented: a measure of phase
      synchrony and a novel measure of intermittent phase desynchronization. These are
      used to quantify the behavior of numerical examples of coupled chaotic
      attractors. Experimental evidence of their contribution to the morphology of the
      human alpha rhythm is then illustrated in a study of EEG recordings from 40
      healthy human subjects. Amplitude-adjusted phase-randomized surrogate data is
      used to test the null hypothesis that the observed patterns of phase coherence
      can be described by purely linear methods. Statistical analysis reveals that this
      null hypothesis can be robustly rejected in a small number (approximately 4%) of
      EEG epochs. These findings are discussed with reference to the adaptive function
      and complex dynamics of the brain.

PMID- 11835609
TI  - Application of an MEG eigenspace beamformer to reconstructing spatio-temporal
      activities of neural sources.
AB  - We have applied the eigenspace-based beamformer to reconstruct spatio-temporal
      activities of neural sources from MEG data. The weight vector of the eigenspace
      based beamformer is obtained by projecting the weight vector of the minimum
      variance beamformer onto the signal subspace of a measurement covariance matrix.
      This projection removes the residual noise-subspace component that considerably
      degrades the signal-to-noise ratio (SNR) of the beamformer output when errors in
      estimating the sensor lead field exist. Therefore, the eigenspace-based
      beamformer produces a SNR considerably higher than that of the minimum-variance
      beamformer in practical situations. The effectiveness of the eigenspace-based
      beamformer was validated in our numerical experiments and experiments using
      auditory responses. We further extended the eigenspace-based beamformer so that
      it incorporates the information regarding the noise covariance matrix. Such a
      prewhitened eigenspace beamformer was experimentally demonstrated to be useful
      when large background activity exists.

PMID- 11835610
TI  - Isotropic resolution diffusion tensor imaging with whole brain acquisition in a
      clinically acceptable time.
AB  - Our objective was to develop a diffusion tensor MR imaging pulse sequence that
      allows whole brain coverage with isotropic resolution within a clinically
      acceptable time. A single-shot, cardiac-gated MR pulse sequence, optimized for
      measuring the diffusion tensor in human brain, was developed to provide whole
      brain coverage with isotropic (2.5 x 2.5 x 2.5 mm) spatial resolution, within a
      total imaging time of approximately 15 min. The diffusion tensor was computed for
      each voxel in the whole volume and the data processed for visualization in three
      orthogonal planes. Anisotropy data were further visualized using a maximum
      intensity projection algorithm. Finally, reconstruction of fiber-tract
      trajectories i.e., "tractography" was performed. Images obtained with this pulse
      sequence provide clear delineation of individual white matter tracts, from the
      most superior cortical regions down to the cerebellum and brain stem. Because the
      data are acquired with isotropic resolution, they can be reformatted in any plane
      and the sequence can therefore be used, in general, for macroscopic neurological
      or psychiatric neuroimaging investigations. The 3D visualization afforded by
      maximum intensity projection imaging and tractography provided easy visualization
      of individual white matter fasciculi, which may be important sites of
      neuropathological degeneration or abnormal brain development. This study has
      shown that it is possible to obtain robust, high quality diffusion tensor MR data
      at 1.5 Tesla with isotropic resolution (2.5 x 2.5 x 2.5 mm) from the whole brain
      within a sufficiently short imaging time that it may be incorporated into
      clinical imaging protocols.

PMID- 11835611
TI  - Timing and connectivity in the human somatosensory cortex from single trial mass
      electrical activity.
AB  - Parallel-distributed processing is ubiquitous in the brain but often ignored by
      experimental designs and methods of analysis, which presuppose sequential and
      stereotypical brain activations. We introduce here a methodology that can
      effectively deal with sequential and distributed activity. Regional brain
      activations elicited by electrical median nerve stimulation are identified in
      tomographic estimates extracted from single trial magnetoencephalographic
      signals. Habituation is identified in both primary somatosensory cortex (SI) and
      secondary somatosensory cortex (SII), often interrupted by resurgence of strong
      activations. Pattern analysis is used to identify single trials with homogeneous
      regional brain activations. Common activity patterns with well-defined
      connectivity are identified within each homogeneous group of single trials across
      the subjects studied. On the contralateral side one encounters distinct sets of
      single trials following identical stimuli. We observe in one set of trials
      sequential activation from SI to SII and insula with onset of SII at 60 msec,
      whereas in the other set simultaneous early co-activations of the same two areas.

PMID- 11835613
TI  - Volumetric model determination of the tibia based on 2D radiographs using a 2D/3D
      database.
AB  - We present a new concept with mathematical background for the construction of a
      three-dimensional (3D) volumetric model of the human tibia based on two
      conventional orthogonal two-dimensional (2D) radiographic images. This approach
      is supported by a computer database containing a collection of 80 2D/3D image
      data sets of individual cadaveric tibiae. For each of these tibiae, the database
      contains digitized 2D orthogonal radiographic images in both anterior and lateral
      views, and the corresponding 3D CT data obtained by computerized tomography. To
      obtain a 3D model of a tibia for a given patient, shape matching is performed.
      The computer finds the most similar tibia to the patient's tibia among the 2D
      radiographic images in the database by applying a matching process. To improve
      accuracy, a 2D image warping procedure can be applied on the slices of the
      selected bone prior to 3D reconstruction. The warping process is controlled by
      the contour data of the two orthogonal views. We found that the 3D model thus
      achieved was useful for virtual preoperative planning and for simulation of the
      internal fixation of long bones.

PMID- 11835612
TI  - Detection of functional connectivity using temporal correlations in MR images.
AB  - Functional connectivity among brain regions has been investigated via an analysis
      of correlations between regional signal fluctuations recorded in magnetic
      resonance (MR) images obtained in a steady state. In comparison with studies of
      functional connectivity that utilize task manipulations, the analysis of
      correlations in steady state data is less susceptible to confounds arising when
      functionally unrelated brain regions respond in similar ways to changes in task.
      A new approach to identifying interregional correlations in steady state data
      makes use of two independent data sets. Regions of interest (ROIs) are defined
      and hypotheses regarding their connectivity are generated in one data set. The
      connectivity hypotheses are then evaluated in the remaining (independent) data
      set by analyzing low frequency temporal correlations between regions. The roles
      of the two data sets are then reversed and the process repeated, perhaps multiple
      times. This method was illustrated by application to the language system. The
      existence of a functional connection between Broca's area and Wernicke's area was
      confirmed in healthy subjects at rest. An increase in this functional connection
      when the language system was actively engaged (when subjects were continuously
      listening to narrative text) was also confirmed. In a second iteration of
      analyses, a correlation between Broca's area and a region in left premotor cortex
      was found to be significant at rest and to increase during continuous listening.
      These findings suggest that the proposed methodology can reveal the presence and
      strength of functional connections in high-level cognitive systems.

PMID- 11835614
TI  - Accuracy evaluation of surface-based registration methods in a computer
      navigation system for hip surgery performed through a posterolateral approach.
AB  - OBJECTIVE: Many computer navigation systems have recently been developed for
      brain surgery, and the use of such systems in orthopedic surgery is increasing.
      Intraoperative registration of preoperative images is one of the most important
      steps in controlling the overall accuracy of computer navigation systems. Various
      parameters, such as CT-scan slice thickness, reconstruction pitch, intraoperative
      data sampling area, and data sampling volume, may affect the accuracy of
      registration. The purpose of this study was to evaluate the effect of the
      aforementioned parameters on the accuracy of registration for hip surgery
      performed through a posterolateral approach, and to find a clinically suitable
      trade-off between accuracy and surgical invasiveness. MATERIALS AND METHODS: One
      cadaveric pelvis and one cadaveric femur were used for this study. Four alumina
      ceramic balls with a diameter of 28 mm and within 1 micrometer of sphericity were
      attached to the pelvis, and three similar balls attached to the femur, to
      determine relative position. CT-scan images of the pelvis and femur were obtained
      with a helical scanner. Three sets of slice thickness and slice pitch were chosen
      for data acquisition, and two additional sets of reconstructed data were made.
      Bone contours were extracted by cutting out the surrounding substrate at a given
      CT number threshold, and surface models of the bone were made from the resultant
      data. The positions of the pelvis and femur were tracked by LED markers attached
      to the bone using an optical three-dimensional position sensor (OPTOTRAK).
      Registration of the computer models to the real objects was performed by
      measuring the position of a certain number of surface points on each object with
      an OPTOTRAK pen-probe. RESULTS AND CONCLUSION: Slice thickness and reconstruction
      pitch affected the accuracy of registration. As the sampling area was expanded
      from the periarticular area to the distant peripheral area, accuracy increased
      slightly. Accuracy did not increase when the whole area was used, but in fact
      decreased, especially in the femur. The positive effect of increasing the number
      of sampling points was saturated at 30 points when the surface of the
      periarticular area was sampled. The following trade-off between accuracy and
      invasiveness, in terms of various parameters of preoperative and intraoperative
      data, is proposed as clinically optimal: perform the CT scan with 3-mm slice
      thickness and 1-mm reconstruction pitch, and sample the periarticular area with
      30 sampling points. With these parameters, the accuracy of registration was 1.2
      mm and 0.9 degrees of bias with 0.7 mm and 0.3 degrees of RMS in the pelvis, and
      1.4 mm and 0.6 degrees of bias with 1.3 mm and 0.3 degrees of RMS in the femur.

PMID- 11835615
TI  - Clinical results of percutaneous pelvic surgery. Computer assisted surgery using
      ultrasound compared to standard fluoroscopy.
AB  - This study presents early results of clinical experience with the application of
      Computer Assisted Surgery (CAS) to percutaneous iliosacral screwing, with
      comparison to a historical series of patients treated using percutaneous
      fluoroscopy. Four patients were instrumented using a CAS system, with 10 screws
      being inserted. Thirty patients were treated by percutaneous fluoroscopic
      screwing, with 51 screws being inserted. The follow-up assessment included the
      following criteria; operative time, parameters of radiation exposure,
      neurological examination, screw placement evaluation on CT-scan, antalgic drug
      consumption, pain, Majeed grading, and loosening of implants. In the CAS group,
      the average radiation time was 0.35 min per patient and 0.14 min per screw. No
      trajectories outside the bone and no postoperative neurological deficits were
      found. In the fluoroscopic group, the average radiation time was 1.03 min per
      patient and 0.6 min per screw. Twelve screws had outside-bone trajectories, and
      iatrogenic neurological deficits were found in seven patients. The average
      operative time was 50 min in the CAS group and 35 min in the fluoroscopic group.
      The present CAS technique shows better placement of iliosacral screws, with no
      outside-bone trajectories and lower radiation exposure.

PMID- 11835616
TI  - Computer-assisted percutaneous transiliac approach to tumorous malformation of
      the sacrum.
AB  - The object of this article is to present a new, minimally invasive, percutaneous
      image-guided technique for surgery of tumorous malformation of the sacrum. Using
      one of the available CAS systems, we developed a navigable working tube through
      which various surgical tools may be very precisely introduced into the tumorous
      malformation. The tube allows us to obtain histological samples and also perform
      tumor resections. For sacral procedures, the working tube was introduced
      percutaneously into the affected area of the sacrum through the sacroiliac joint
      with computer assistance. For successful matching, small titanium screws were
      inserted into the sacrum and pelvis percutaneously before CT examination to give
      precise landmark points. We have used the method in 12 cases. The aim of the
      surgery in biopsy cases was to obtain samples for histological diagnoses of
      unknown tumors. In the cases of tumor resection (all were metastatic), the
      indication was to obtain neurological decompression and decreased local pain. The
      pain response was very effective in all cases. The transiliac percutaneous
      approach to the sacrum has proven to be a safe and well-designed procedure. It
      can even be performed under local anesthesia, and is thus a very effective
      minimally invasive tool for obtaining pain relief in cases of sacral metastasis
      involving the first, second, and third segments.

PMID- 11835617
TI  - Computer-assisted implantation of total knee prostheses: a case-control
      comparative study with classical instrumentation.
AB  - A navigation system should improve the quality of a total knee prosthesis
      implantation in comparison to that obtained with the classical, surgeon
      controlled operative technique. The authors implanted 30 total knee prostheses
      with an infrared navigation system (Orthopilot, Aesculap, Tuttlingen, Germany).
      The quality of implantation was studied on postoperative long-leg coronal and
      lateral X-rays, and compared to a control group of 30 matched-paired total knee
      prostheses of the same type (Search prosthesis, Aesculap, Tuttlingen, Germany)
      implanted with a classical, surgeon-controlled technique. An optimal mechanical
      femorotibial angle (177 to 183 degrees) was obtained in 25 cases in the study
      group and 21 cases in the control group (p > 0.05). Similar differences were seen
      for the coronal and sagittal orientations of both tibial and femoral components.
      Globally, 23 cases in the study group and 8 cases in the control group were
      implanted in an optimal manner for all studied criteria (p < 0.001). The
      navigation system used allows a significant improvement in the quality of
      implantation of a total knee prosthesis in comparison to that obtained with a
      classical, surgeon-controlled instrumentation, and long-term outcome could
      consequently be improved.

PMID- 11835618
TI  - Intraoperative accuracy evaluation of virtual fluoroscopy--a method for
      application in computer-assisted distal locking.
AB  - Virtual fluoroscopy integrates intraoperative C-arm fluoroscopy as an imaging
      modality for surgical navigation. In the operating room, the conditions for
      application of virtual fluoroscopy may be impaired. In such situations, the
      surgeon is interested in an intraoperative check to decide whether the accuracy
      available is sufficient to perform the scheduled procedure. The test principle is
      to include an artificial landmark within the fluoroscopic images acquired for
      virtual fluoroscopy. As this landmark is fixed outside the patient, it can be
      touched with the referenced tool prior to performing the procedure. A mismatch
      between the actual tool position at the landmark and the virtual tool position as
      visualized on the computer screen allows estimation of the system's accuracy. The
      principle described was designed for detection of inaccuracies resulting from
      input of nonoptimal data to the navigation system. The method was successfully
      applied during computer-assisted distal locking of intramedullary implants, and
      the test principle might be adapted for other applications of virtual
      fluoroscopy.

PMID- 11835619
TI  - Tube angulation improves angiographic targeting of arteriovenous malformations
      during stereotactic radiosurgery.
AB  - Stereotactic radiosurgery using the 201 Cobalt-60 source Gamma Knife has been an
      effective method for obliterating selected cerebral arteriovenous malformations
      (AVMs). For more than 20,000 patients worldwide, angiography under stereotactic
      conditions has been the main imaging modality for defining and targeting the AVM
      nidus. The role of angulation of the X-ray tube for angiographic localization of
      the AVM during stereotactic Gamma Knife radiosurgery was studied with a phantom.
      Using current dose-planning software, tube angulation facilitated target
      visualization, improved three-dimensional dose planning, and has been consistent
      with the increased probability of complete nidus obliteration.

PMID- 11835620
TI  - Discovery in toxicology: mediation by gene expression array technology.
AB  - Toxicogenomics is a term that represents the merging of toxicology with novel
      genomics techniques. Data generated in the new-age era of toxicology is
      relatively complex, requires new bioinformatics tools for adequate
      interpretation, and allows for the rapid generation of testable hypotheses.
      Hazard identification and risk assessment processes will advance from the use of
      genomics techniques, which will lead to greater understanding of mechanism(s) of
      action of toxicants, development of novel biomarkers of exposure and effect, and
      better identification of sensitive subpopulations.

PMID- 11835621
TI  - Cloning, sequencing, and characterization of CYP1A1 cDNA from leaping mullet
      (Liza Saliens) liver and implications for the potential functions of its
      conserved amino acids.
AB  - A 2,037 bp CYP1A1 cDNA (GenBank AF072899) was cloned through screening of a
      lambdaZipLox cDNA library constructed from the liver of a leaping mullet (Liza
      saliens) fish captured from Izmir Bay on the Aegean coast of Turkey using rainbow
      trout CYP1A1 cDNA as a probe. This clone has a 130 bp 5'-flanking region, a 1,563
      bp open reading frame (ORF) encoding a 521-amino acid protein (58,972 Da), and a
      344 bp 3'-untranslated region without a poly (A) tail. Alignment of the deduced
      amino acids of CYP1A1 cDNAs showed 58% and 69-96% identities with human and 12
      other fish species, respectively. Southern blot analysis suggested that this
      CYP1A1 cDNA was from a single-copy gene. Based on the comparison with CYP1A1
      genes reported for fish and mammals, the leaping mullet CYP1A1 gene is probably
      split into 7 exons. The intron insertion sites were predicted. Alignment of the
      CYP1A1 cDNA encoded amino acids from 13 fish and 7 mammalian species disclosed
      differences in highly conserved amino acids between aquatic and land vertebrates.
      The possible associated secondary structure; conserved motifs and substrate
      binding sites were discussed. The phylogenetic relationships of CYP1A1s among 13
      fish species were analyzed by a distance method.

PMID- 11835622
TI  - Role of astrocytes in trimethyltin neurotoxicity.
AB  - Although the neurotoxicity of trimethyltin (TMT) is well known, mechanisms are
      still not clear. Glia have been proposed to mediate the toxic action of TMT on
      nerve cells. Accordingly, the effects of TMT were tested in primary neuronal
      cultures from rat cerebellum and compared to effects in astrocytes and mixed
      cultures. Neuronal damage observed following TMT exposure was less in the
      presence of astrocytes and astrocytes alone were resistant to TMT. Thus,
      astrocytes have a protective effect against TMT-induced neurotoxicity. TMT caused
      an oxidative stress in granule cell cultures involving a variety of oxidative
      species (O2)*-, H2O2, NO), but astrocytes were less sensitive to TMT-induced
      oxidative species generation. Antioxidants, glutathione and 7-nitroindazole
      attenuated neuronal cell death induced by TMT. It appears that oxidative stress
      mediates a large part of the destructive action of TMT in neuronal cultures. The
      presence of astrocytes appears to modulate TMT-induced oxidative stress so that
      TMT causes only a small increase in lipid peroxidation in mouse brain after
      systemic administration. Thus, TMT induces a pronounced oxidative stress in
      cultured neurons, but when astrocytes are present, oxidative species play a
      lesser role in the neurotoxic action of TMT.

PMID- 11835623
TI  - Inhibition of forskolin-stimulated cAMP formation in vitro by paraoxon and
      chlorpyrifos oxon in cortical slices from neonatal, juvenile, and adult rats.
AB  - Parathion (PS) and chlorpyrifos (CPF) are organophosphorus insecticides, which
      elicit toxicity following biotransformation to the potent acetylcholinesterase
      inhibitors, paraoxon (PO) and chlorpyrifos oxon (CPO). Both oxons have also been
      shown to interact directly with muscarinic receptors coupled to inhibition of
      adenylyl cyclase. Immature animals are more sensitive than adults to the acute
      toxicity of PS and CPF but little is known regarding possible age-related
      differences in interactions between these toxicants and muscarinic receptors. We
      compared the inhibition of forskolin-stimulated cAMP formation by PO and CPO (1
      nM-1 mM) in vitro in brain slices from 7-, 21-, and 90-day-old rats to the
      effects of well-known muscarinic agonists, carbachol and oxotremorine (100
      microM). Both agonists inhibited cAMP formation in tissues from all age groups
      and both were more effective in adult and juvenile (20-26% inhibition) than in
      neonatal (12-13% inhibition) tissues. Atropine (10 microM) completely blocked
      agonist-induced inhibition in all cases. PO maximally inhibited (37-46%) cAMP
      formation similarly in tissues from all age groups, but atropine blocked those
      effects only partially and only in tissues from 7-day-old rats. CPO similarly
      inhibited cAMP formation across age groups (27-38%), but ATR was partially
      effective in tissues from all three age groups. Both oxons were markedly more
      potent in tissues from younger animals. We conclude that PO and CPO can directly
      inhibit cAMP formation through muscarinic receptor-dependent and independent
      mechanisms and that the developing nervous system may be more sensitive to these
      noncholinesterase actions.

PMID- 11835624
TI  - Di-tert-butylhydroxylated flavonoids protect endothelial cells against oxidized
      LDL-induced cytotoxicity.
AB  - The protective effect of di-tert-butylhydroxylated flavonoids (chalcones and
      arylidenes) against minimally oxidized LDL (mO-LDL)-induced cytotoxicity was
      studied in cultured bovine aortic endothelial cells. Most of the tested compounds
      decreased aldehydes formation in medium containing mO-LDL, but their capacity to
      inhibit LDL oxidation in the cellular medium was not sufficient to totally reduce
      the cellular toxicity of mO-LDL. Most of the tested flavonoids improved the
      integrity of cells exposed to mO-LDL, whereas butylated hydroxytoluene was
      ineffective and quercetin worsened the toxicity of mO-LDL. Moreover these
      flavonoids induced an increase in GSH cellular levels and their protective
      effects might be because of their inability to reduce metal ion. Arylidene 6
      substituted at position 7 by a hydroxyl group was the most potent compound.

PMID- 11835625
TI  - Hepatotoxicity and cholestasis in rats induced by the sesquiterpene, 9-oxo-10,11
      dehydroageraphorone, isolated from Eupatorium adenophorum.
AB  - Eupatorium adenophorum leaves cause hepatotoxicity and cholestasis in rats. The
      hepatotoxicant has been characterized as 9-oxo-10,11-dehydroageraphorone (ODA), a
      cadinene sesquiterpene. Oral administration of ODA, mixed in feed to rats, caused
      jaundice in 24 h. The liver of the intoxicated animals had focal areas of
      hepatocellular necrosis, proliferation, and dilation of bile ducts with
      degenerative changes in the lining epithelium. There was marked increase in the
      conjugated form of plasma bilirubin and in the activities of the enzymes
      glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, alkaline
      phosphatase, lactate dehydrogenase, gamma-glutamyltranspeptidase, glutamate
      dehydrogenase, and 5'-nucleotidase. The histopathological lesions in liver and
      biochemical profile of marker enzymes show that ODA induced hepatotoxicity and
      cholestasis in rats. This is the first report on the toxicity of a cadinene
      sesquiterpene in rats.

PMID- 11835626
TI  - Accelerated development of uroporphyria in mice heterozygous for a deletion at
      the uroporphyrinogen decarboxylase locus.
AB  - Three weeks after a single dose of iron-dextran and Aroclor 1254, mice maintained
      continuously on delta-aminolevulinic acid supplemented drinking water showed
      significantly elevated levels of hepatic uroporphyrin and depressed (25% of
      normal) uroporphyrinogen decarboxylase (URO-D) activity. Depressed URO-D activity
      was paralleled by the ability of heat denatured cytosol to inhibit rhURO-D
      activity. Mice heterozygous for a targeted disruption at the URO-D locus (URO-D+/
      ) exhibited half the URO-D activity of homozygous controls prior to treatment.
      After treatment, these animals showed URO-D activity and rhURO-D inhibitory
      activity comparable to similarly treated wild type (URO-D +/+) mice but with
      significantly greater uroporphyrin accumulation. With only 10 days of treatment,
      URO-D +/- but not URO-D +/+ mice showed changes similar in magnitude to those
      seen after 21 days. Prior to treatment, URO-D genotype did not influence overall
      hepatic P450 concentration in either sex and there was no significant difference
      between sexes. The treatment regimen significantly elevated P450 in animals of
      either URO-D genotype and in both sexes, although the induction response at the
      10-day point was attenuated in URO-D +/- mice. From differences in the CO
      absorbance maximum, and by P450 activity analysis, this attenuated induction
      response resulted from an attenuation of the CYP2B not the CYP1A induction.

PMID- 11835628
TI  - In vitro human phase I metabolism of xenobiotics I: pesticides and related
      chemicals used in agriculture and public health, September 2001.
AB  - Human phase I enzymes and their isoforms that metabolize pesticides are listed in
      a database that will be updated periodically. This initial version includes
      enzymes and isoforms that metabolize organophosphorus insecticides,
      chloroacetamide herbicides and triazine herbicides.

PMID- 11835629
TI  - Sequencing, expression, and characterization of cDNA expressed flavin-containing
      monooxygenase 2 from mouse.
AB  - The cDNA clone of mouse flavin-containing monooxygenase 2 (FMO2) was obtained as
      an expressed sequence tag (EST) isolated from a female mouse kidney cDNA library
      from the I.M.A.G.E. consortium (I.M.A.G.E. CloneID 1432164). Complete sequencing
      of the EST derived a nucleotide sequence for mouse FMO2, which contains 112 bases
      of 5' flanking region, 1607 bases of coding region, and 309 bases of 3' flanking
      region. This FMO2 sequence encodes a protein of 535 amino acids including two
      putative pyrophosphate binding sequences (GxGxxG/A) beginning at positions 9 and
      191. Additionally, this mouse FMO protein sequence shows 87 and 86% homology to
      rabbit and human FMO2 respectively. The mouse FMO2 sequence was subcloned into
      the expression vector pJL-2, a derivative of pKK233-2 and used to transform XL1
      Blue Escherichia coli. FMO activity in particulate fractions isolated from
      isopropyl-beta-D-thiogalactopyanoside (IPTG) induced cells was heat stable (45
      degrees C for 5 min) and demonstrated optimal activity at a relatively high pH of
      10.5. The expressed FMO2 enzyme showed catalytic activity towards the FMO
      substrate methimazole and further analysis of E. coli fractions utilizing NADPH
      oxidation demonstrated that the mouse FMO2 enzyme also exhibits catalytic
      activity towards thiourea, trimethylamine, and the insecticide phorate.

PMID- 11835630
TI  - Extensive protein carbonylation precedes acrolein-mediated cell death in mouse
      hepatocytes.
AB  - Allyl alcohol hepatotoxicity is mediated by an alcohol dehydrogenase-derived
      biotranformation product, acrolein. This highly reactive alpha,beta-unsaturated
      aldehyde readily alkylates model proteins in vitro, forming, among other
      products, Michael addition adducts that possess a free carbonyl group. Whether
      such damage accompanies acrolein-mediated toxicity in cells is unknown. In this
      work we established that allyl alcohol toxicity in mouse hepatocytes involves
      extensive carbonylation of a wide range of proteins, and that the severity of
      such damage to a subset of 18-50 kDa proteins closely correlated with the degree
      of cell death. In addition to abolishing cytotoxicity and glutathione depletion,
      the alcohol dehydrogenase inhibitor 4-methyl pyrazole strongly attenuated protein
      carbonylation. Conversely, cyanamide, an aldehyde dehydrogenase inhibitor,
      enhanced cytotoxicity and protein carbonylation. Since protein carbonylation
      clearly preceded the loss of membrane integrity, it may be associated with the
      toxic process leading to cell death.

PMID- 11835631
TI  - Beneficial effect of nitric oxide synthase inhibitor on hepatotoxicity induced by
      allyl alcohol.
AB  - The effect of aminoguanidine (a selective inhibitor of inducible nitric oxide
      synthase) on allyl alcohol-induced liver injury was assessed by the measurement
      of serum ALT and AST activities and histopathological examination. When
      aminoguanidine (50-300 mg/kg, i.p.) was administered to mice 30 min before a
      toxic dose of allyl alcohol (75 microL/kg, i.p.), significant changes related to
      liver injury were observed. In the presence of aminoguanidine the level of ALT
      and AST enzymes were significantly decreased. All symptoms of liver necrosis
      produced by allyl alcohol toxicity almost completely disappeared when animals
      were pretreated with aminoguanidine at 300 mg/kg. Depletion of hepatic
      glutathione as a consequence of allyl alcohol metabolism was minimal in mice
      pretreated with aminoguanidine at 300 mg/kg. It was found that the inhibition of
      toxicity was not due to alteration in allyl alcohol metabolism since
      aminoguanidine did not effect alcohol dehydrogenase activity both in vivo and in
      vitro.

PMID- 11835632
TI  - Differential sensitivities of plant and animal mitochondria to the herbicide
      paraquat.
AB  - Paraquat herbicide is toxic to animals, including humans, via putative toxicity
      mechanisms associated to microsomal and mitochondrial redox systems. It is also
      believed to act in plants by generating highly reactive oxygen free radicals from
      electrons of photosystem I on exposure to light. Paraquat also acts on non
      chlorophyllous plant tissues, where mitochondria are candidate targets, as in
      animal tissues. Therefore, we compared the interaction of paraquat with the
      mitochondrial bioenergetics of potato tuber, using rat liver mitochondria as a
      reference. Paraquat depressed succinate-dependent mitochondrial Delta(psi), with
      simultaneous stimulation of state 4 O2 consumption. It also induced a slow time
      dependent effect for respiration of succinate, exogenous NADH, and N,N,N',N'
      tetramethyl-p-phenylenediamine (TMPD)/ascorbate, which was more pronounced in rat
      than in potato mitochondria. However, with potato tuber mitochondria, the
      Delta(psi) promoted by complex-I-dependent respiration is insensitive to this
      effect, indicating a protection against paraquat radical afforded by complex I
      redox activity, which was just the reverse of to the findings for rat liver
      mitochondria. The experimental set up with the tetraphenyl phosphonium (TPP+)
      electrode also indicated production of the paraquat radical in mitochondria, also
      suggesting its accessibility to the outside space. The different activities of
      protective antioxidant agents can contribute to explain the different
      sensitivities of both kinds of mitochondria. Values of SOD activity and alpha
      tocopherol detected in potato mitochondria were significantly higher than in rat
      mitochondria, which, in turn, revealed higher values of lipid peroxidation
      induced by paraquat.

PMID- 11835634
TI  - Angiographic outcome after intracoronary X-Sizer helical atherectomy and
      thrombectomy: first use in humans.
AB  - The objective of this study was to evaluate the early angiographic outcome in the
      first human subjects who underwent intracoronary atherectomy and thrombectomy
      using the X-Sizer helical cutting and aspiration system. Percutaneous coronary
      interventions in patients with thrombo-occlusive disease or friable degenerative
      saphenous vein grafts are associated with considerable periprocedural morbidity
      and mortality, predominantly related to microscopic distal embolization. X-Sizer
      catheter system is a novel atherectomy and thrombectomy device that consists of a
      helix cutter connected to a handheld motor drive unit and a vacuum collection
      chamber for aspiration of excised atheroma, thrombus, and debris. Quantitative
      coronary angiography was obtained in 14 patients before and after X-Sizer
      extraction atherectomy with adjunctive balloon angioplasty and stenting. Thirteen
      native coronary arteries and one saphenous vein graft were treated. Mean
      preprocedural reference vessel diameter was 3.06 +/- 0.66 mm. There were 71.4%
      AHA/ACC type B2 and C lesions. Preprocedural thrombus was present in nine
      patients and total occlusion in 64% of cases. Minimal luminal diameter was
      increased from 0.29 +/- 0.47 mm to 1.32 +/- 0.64 mm, a gain of 1.04 +/- 0.69 mm
      after atherectomy. Final total gain was 1.47 +/- 0.61 mm. Mean diameter stenosis
      was reduced from 89.3% to a final residual stenosis of 14.4%. Postatherectomy
      distal embolization occurred in one patient who had heavy preprocedural thrombus
      burden. No episodes of perforation, distal coronary spasm, abrupt closure, or
      slow/no-reflow occurred. The angiographic analysis of the first cohort of human
      subjects suggests that X-Sizer helical atherectomy is a feasible method of
      removing occlusive tissue or thrombus in coronary artery disease with a low
      angiographic complication rate. A large-scale randomized phase II clinical trial
      is underway to determine the ultimate safety and efficacy of this device in
      thrombo-occlusive native coronary arteries and saphenous vein grafts.

PMID- 11835635
TI  - Thrombo-atherectomy: hope for pesky thrombus-containing lesions?

PMID- 11835636
TI  - Late coronary stent thrombosis: early vs. late stent thrombosis in the stent era.
AB  - The incidence of coronary stent thrombosis is < 1%-2% in recent studies, with the
      highest-risk period considered to be the first 30 days following stent
      implantation. Recently, stent thrombosis after 30 days has been reported in
      patients undergoing brachytherapy with stenting. We reviewed the incidence of
      stent thrombosis causing myocardial infarction in nonbrachytherapy patients at
      our institution between 1 January 1996 and 30 November 1999. A case control
      methodology was employed with a 1:3 ratio of stent thrombosis to control
      patients. Of 1,191 patients undergoing coronary stenting, acute (< 24 hr) plus
      subacute (1-30 days) stent thrombosis occurred in 0.92% (11 of 1,191 patients). A
      further 0.76% (9 of 1,191 patients) developed late stent thrombosis after 30
      days. There were no clinical or angiographic features at the time of the initial
      procedure that were associated with stent thrombosis as an entire group compared
      with control group, but early (acute and subacute) stent thrombosis patients had
      a smaller final stent minimal lumen diameter and longer stent length compared
      with patients who had late stent thrombosis or controls. Late stent thrombosis
      occurs in nonbrachytherapy patients and is almost as frequent as early stent
      thrombosis. Further studies are required to determine whether longer-term
      poststent pharmacological treatment may decrease or prevent this complication.

PMID- 11835637
TI  - Stent thrombosis: it's never too late!

PMID- 11835638
TI  - Aspirin alone antiplatelet regimen after intracoronary placement of the
      Carbostent: the ANTARES study.
AB  - The effect of stent coatings in preventing early thrombotic occlusion remains to
      be proved. The purpose of this study was to evaluate the safety and efficacy of
      the Carbostent, a new coronary stent with a nonthrombogenic coating (Carbofilm),
      in 110 consecutive patients (73.6% men, mean age 61 +/- 9 years) who met
      prespecified clinical and angiographic inclusion criteria and were treated with
      aspirin monotherapy after stenting. Stable angina (75.5%), unstable angina
      (18.2%), and silent ischemia (6.3%) were clinical indications for coronary
      revascularization. Patients received 10,000 U of heparin and no IIb/IIIa
      inhibitors or postprocedural heparin. Complex lesion characteristics (B2, C) were
      present in 39 out of 129 (30.2%) lesions. Mean lesion length was 15.6 +/- 7.4 mm,
      and 32% of the lesions were >15 mm (range 16-52 mm). Small coronary vessels (<3.0
      mm) were treated in 28% of the cases. A total of 165 Carbostent were used in 129
      coronary lesions of the 110 patients. Single-vessel stenting was performed in 97
      (88%) patients and multivessel stent placement in 13 (12%) patients. The mean
      length of the stented segment was 21 +/- 13 mm (range 9-95 mm). Procedural and
      clinical success was achieved in all patients. At 1-month follow-up, there were
      no stent thrombosis or other major adverse cardiac events. We observed 2 (1.8%)
      non-Q-wave myocardial infarctions and 2 (1.8%) vascular complications. This study
      indicates that the Carbostent may prevent stent thrombosis in selected patients
      treated with aspirin only. A randomized study comparing aspirin alone versus
      combined ticlopidine and aspirin after Carbostent implantation will be needed to
      confirm these results.

PMID- 11835640
TI  - Intra-aortic balloon pump placement following aorto-iliac angioplasty and stent
      placement.
AB  - Approximately 20% of patients are unable to receive an intra-aortic balloon pump
      (IABP) due to aorto-iliac atherosclerotic disease. Aorto-iliac stenoses can be
      managed with angioplasty or stent placement; however, there are limited data
      about this strategy to facilitate IABP placement. Thirty-seven IABPs were placed
      in 35 patients. A total of 45 revascularization procedures were performed. With
      revascularization, the minimal lumen diameter increased from 2.78 +/- 1.46 to
      6.75 +/- 2.36 mm (P < 0.0001). Limb ischemia occurred following 2/37 (5%) IABP
      insertions. Limb ischemia was managed with IABP removal and angioplasty. The
      mortality rate was 32%. Mortality was more common with chronic renal
      insufficiency (8/11, 73%; P = 0.0014), dialysis-dependent renal failure (3/3,
      100%; P = 0.028), and presentation with acute myocardial infarction (8/15
      patients, 53%; P = 0.036). Although no patients required vascular surgery for
      limb ischemia, one patient required surgery for bleeding. Angioplasty or stenting
      to facilitate IABP placement in patients with peripheral vascular disease is safe
      and effective.

PMID- 11835639
TI  - Patterns of in-stent restenosis after placement of NIR gold-coated stents in
      unselected patients.
AB  - The aim of this study was to assess the incidence and angiographic patterns of in
      stent restenosis 6 months after the implantation of NIR gold-coated stents in an
      unselected patient population. One hundred and sixteen consecutive patients were
      treated with the implantation of 149 NIR gold-coated stents. The majority of the
      patients (52%) had unstable angina or acute myocardial infarction. The baseline
      lesion morphology was complex in 78% of cases; the mean lesion length was 18 +/-
      5 mm. The procedural success rate was 97%. Subacute stent thrombosis occurred in
      three patients (2.6%). During the 6-month follow-up, there were 2 deaths and 22
      subjects (19.5%) underwent target vessel revascularization. The 6-month event
      free survival was 60%. The angiographic restenosis rate was 32%. In 83% of the
      cases, the morphology of the restenosis was proliferative; in the remaining 17%,
      it presented as total occlusion. In conclusion, the restenosis rate after NIR
      gold-coated stent implantation in high-risk patients is similar to that reported
      using other stent designs. However, restenosis was always diffuse, involving the
      overall stent length and extending beyond the margins, thus indicating a greater
      proliferative neointimal response to this device.

PMID- 11835641
TI  - A protocol for prevention of radiographic contrast nephropathy during
      percutaneous coronary intervention: effect of selective dopamine receptor agonist
      fenoldopam.
AB  - Radiographic contrast nephropathy (RCN), acute worsening of renal function due to
      contrast agents, can occur in 15%-40% of patients with baseline renal dysfunction
      undergoing percutaneous coronary intervention (PCI) and is associated with
      increased morbidity and in-hospital mortality. The purpose of this study was to
      evaluate whether the selective dopamine-1 (DA-1) receptor agonist fenoldopam
      would be beneficial in patients with chronic renal insufficiency (CRI) undergoing
      PCI and also to design a protocol for prevention of RCN. We analyzed 150
      consecutive patients with CRI [baseline serum creatinine (BSCr) +/- 1.5% mg] who
      underwent PCI and received fenoldopam during and after the procedure, in addition
      to saline hydration. RCN, defined as > 25% increase of BSCr 48-72 hr after PCI,
      occurred in 4.7% (n = 7) of 150 PCI patients receiving fenoldopam and 3.5% in
      diabetics (n = 85) vs. 6.1% in nondiabetics (n = 65; P = NS). No patients
      required dialysis. The observed 4.7% incidence of RCN with fenoldopam was
      significantly lower than 18.8% incidence in the historical control group (P <
      0.001). Our data suggest that fenoldopam is a useful adjunct in the prevention of
      RCN during PCI, especially in diabetics.

PMID- 11835642
TI  - Prognostic value of cardiac troponin I elevation after percutaneous coronary
      intervention in patients with chronic renal insufficiency: a 12-month outcome
      analysis.
AB  - Serum cardiac troponin I (cTnI) is a highly specific marker for myocardial damage
      in patients with chronic renal insufficiency (CRI), unlike creatine kinase
      myocardial band fraction (CK-MB), which may be elevated in the absence of
      myocardial injury in patients with CRI. We studied 116 consecutive CRI patients
      (serum creatinine +/- 1.8 mg/dL, not on dialysis) with normal baseline cTnI
      levels who underwent successful percutaneous coronary intervention (PCI).
      Patients were divided into two groups: group 1, elevated postprocedural cTnI (n =
      50), and group 2, normal cTnI (n = 66). Patients with elevated cTnI were older
      and had a higher incidence of postinfarction angina and lower creatinine
      clearance compared to patients who did not have cTnI elevation. Atheroablative
      devices (rotational and directional atherectomy and excimer laser coronary
      angioplasty) were more frequently used in group 1 patients (27.1% vs. 18.5%; P =
      0.04). In-hospital mortality, cardiac mortality, and Q-wave myocardial infarction
      rates did not differ between the two groups. At 12-month follow-up, total
      mortality rates were significantly higher in group 1 (28.0% vs. 9.9%; P = 0.002).
      Multivariate analysis showed that cTnI was an independent predictor of late
      mortality (OR = 2.26; CI = 1.07-4.77; P = 0.03). Thus, in patients with CRI,
      elevated cTnI levels after successful PCI is an important predictor of poor long
      term outcome. Our data suggest that patients with cTnI elevation > 3 times above
      normal values are particularly at higher risk.

PMID- 11835643
TI  - Biomarkers, biometrics, and biology.

PMID- 11835644
TI  - Multicenter Palmaz stent renal artery stenosis revascularization registry report:
      four-year follow-up of 1,058 successful patients.
AB  - Palmaz-Schatz stent revascularization of renal artery stenosis was successfully
      performed on 1,058 patients who were entered into a voluntary, multicenter
      registry. The revascularization procedures were performed because of poorly
      controlled hypertension, preservation of renal function, and congestive heart
      failure. All 1,058 patients were eligible for > or =6-month clinical follow-up,
      which focused on subsequent renal function, blood pressure, number of
      antihypertensive medications, and survival. At 4-year follow-up, systolic and
      diastolic blood pressures had significantly decreased (168 +/- 27 mm Hg to 147 +/
      21 mm Hg, and 84 +/- 15 to 78 +/- 12 mm Hg; P < 0.05) and the blood pressure
      appeared to be more facilely controlled as indicated by the concomitant decrease
      in number of antihypertensive medications (2.4 +/- 1.1 to 2.0 +/- 1.0; P < 0.05).
      Serum creatinine had also significantly decreased (1.7 +/- 1.1 to 1.3 +/- 0.8
      mg/dl; P < 0.05). The cumulative probability of survival was 74% +/- 3% at 4
      years. Survival was good for patients with normal (85% +/- 3%) baseline renal
      function, fair (78% +/- 5%) with mildly impaired renal function, and poor (49% +/
      5%) with severely impaired renal function (baseline creatinine > or =2.0 mg/dl).
      The combination of impaired renal function and bilateral disease adversely
      effected survival (unilateral 55% +/- 6% vs. bilateral 36% +/- 11%; P < 0.05).
      Renal artery stent revascularization, in the presence of normal or mildly
      impaired renal function, had a beneficial effect on blood pressure control and on
      renal function (through stabilization or improvement). Survival was adversely
      effected by renal dysfunction despite adequate revascularization. Perhaps early
      diagnosis of renal artery stenosis and adequate revascularization prior to the
      onset of renal dysfunction could beneficially impact blood pressure control,
      preserve or prevent deterioration of renal function, and improve patient
      survival.

PMID- 11835645
TI  - Transcatheter closure of patent foramen ovale in patients with paradoxical
      embolism: intermediate-term risk of recurrent neurological events.
AB  - Closure of patent foramen ovale (PFO) has been proposed as an alternative to
      anticoagulation in patients with presumed paradoxical emboli. We report our
      preliminary intermediate results of patients who underwent transcatheter PFO
      closure for paradoxical embolism using DAS-Angel Wings occluder or Amplatzer
      devices. Eighteen patients (8 male/10 female) underwent catheter closure of their
      PFOs at a median age of 42 years. The complete closure rate was 67% immediately
      after the procedure and 100% at a mean follow-up interval of 2.2 +/- 1.8 years.
      The mean fluoroscopy time and procedure time in the Amplatzer group were 8.5 +/-
      3.2 min and 65 +/- 21 min, respectively, which were significantly shorter than
      those of DAS-Angel Wings group (18.9 +/- 4.7 min and 137 +/- 28 min,
      respectively). There were no recurrent embolic neurological events following
      device placement in this subset of patients. No complications were encountered
      either during or after the closure procedure. In conclusion, transcatheter
      closure of PFO seems to be an effective alternative therapy in the prevention of
      presumed paradoxical emboli. Further study is needed to identify patients most
      likely to benefit from this intervention.

PMID- 11835646
TI  - The case for closing PFOs.

PMID- 11835647
TI  - Noncoronary transradial angioplasty with coronary equipment: a less invasive
      technique.
AB  - As the safety and feasibility of the transradial approach for percutaneous
      coronary interventions have already been established by many series, we evaluate
      the safety and feasibility of this approach in noncoronary interventions such as
      renal, celiac, mesenteric, and subclavian angioplasty procedures. We present here
      our preliminary experience of noncoronary interventions via the transradial
      approach using coronary equipment with 100% technical and clinical success. Nine
      noncoronary interventions were performed in seven patients (five renal, two
      celiac, one mesenteric and subclavian angioplasty each). The advantage of this
      approach is that it limits arterial wall damage as well as potential distal
      embolization by the use of small guiding catheters and 0.014" guidewires. The
      only limitation of this approach for noncoronary interventions is the guiding
      catheter length in tall patients and the unavailability of large coronary
      balloons for subclavian, celiac, and renal interventions. With the
      miniaturization of equipment and improvements in technique, this approach will
      also become an excellent alternative for noncoronary interventions.

PMID- 11835648
TI  - Transradial approach for coronary angioplasty in the setting of acute myocardial
      infarction: a dual-center registry.
AB  - Although transradial angioplasty has been shown to have no major entry site
      related complications, its clinical applicability for balloon angioplasty and
      stenting in acute myocardial infarction (AMI) is unclear. In order to assess the
      feasibility, safety, and clinical outcome of transradial access for coronary
      angioplasty (PTCA) and stenting during AMI, transradial angioplasty for AMI was
      registered on a prospective database at two European sites (A and B) with
      experience in the radial approach (RA); 6 Fr catheters with an inner lumen of at
      least 0.064" and low-profile rapid-exchange balloons were used. Primary success
      rates and procedural complications of 6 Fr RA were determined and compared to 6
      Fr femoral approach (FA) procedures. A total of 1,224 AMI patients entered the
      registry. Study site A enrolled 185 RA patients (13.6% AMI) and study site B 92
      RA patients (63.4%). Patient baseline demographics were similar in both study
      centers and showed no differences between RA and FA patients, except a more
      frequent use of abciximab in study site B compared to A. PTCA was successful in >
      95% of both RA and FA patients. Total procedural time did not differ between RA
      and FA patients. Severe access site-related bleeding complications, however, were
      observed in FA patients only: study site A used closure devices routinely and
      found 2% severe bleedings; study site B used no closure device for FA patients
      and observed 7% severe bleedings. In selected patients and in experienced hands,
      transradial PTCA in AMI has a high success rate, is clinically safe, and could
      become an attractive alternative access site for patients being at high or even
      low risk for bleeding complications.

PMID- 11835649
TI  - Transcatheter treatment of muscular ventricular septal defect and pulmonary
      valvar stenosis in an infant.
AB  - An 11-month-old, 8 kg girl with muscular ventricular septal defect and pulmonary
      valvar stenosis had successful transcatheter treatment of both anomalies. The
      stenotic pulmonary valve was dilated first by balloon catheter, then the VSD was
      approached and closed using a 6 mm Amplatzer VSD occluder device. Due to
      technological improvements, transcatheter techniques are more and more the
      procedure of choice in a larger number of congenital heart diseases in younger
      and younger patients.

PMID- 11835650
TI  - Infective endocarditis resulting from CardioSEAL closure of a patent foramen
      ovale.
AB  - Patent foramen ovale and atrial septal aneurysm are associated with an increased
      risk of cryptogenic stroke and recurrent thromboembolic events. Percutaneous
      closure is a therapeutic option to medical therapy and surgical closure. We
      present the first case of endocarditis associated with a CardioSEAL device
      closing a patent foramen ovale.

PMID- 11835652
TI  - New stent design for autologous venous graft-covered stent preparation: first
      human application for sealing of a coronary aneurysm.
AB  - In this case report, we present the first clinical application of a new stent
      design for autologous venous graft-covered stent preparation. This stent consists
      of a main body, resembling the configuration of conventional stents, and two
      connecting arms at the edges of the stent for the stabilization of the venous
      graft on the external surface of the stent. This new stent design was applied in
      a patient with an aneurysm in a stented segment in the right coronary artery. The
      immediate and long-term angiographic evaluation after the covered stent
      implantation showed complete sealing of the aneurysm without restenosis.

PMID- 11835653
TI  - Extraction of large intracoronary thrombus in acute myocardial infarction by
      percutaneous Fogarty maneuver: intentional abuse of a novel interventional
      device.
AB  - Intracoronary thrombus in the infarct-related artery remains a challenge for
      interventional catheter-based techniques in acute myocardial infarction and may
      result in severe complications due to distal embolization. We describe a patient
      with acute myocardial infarction in whom a large intracoronary thrombus of the
      left anterior descending coronary artery was successfully removed by percutaneous
      Fogarty maneuver using an expanded filter protection device.

PMID- 11835654
TI  - Repeated intracoronary beta radiation for recurrent in-stent restenosis.
AB  - More than 70% of percutaneous coronary interventions are followed by a stent
      implantation. In-stent restenosis still occurs in 20-30% of patients and remains
      a therapeutic challenge. At present only vascular brachytherapy has been shown to
      be an effective treatment option. We report here one case of recurrent in-stent
      restenosis after vascular brachytherapy that was successfully treated by a second
      beta radiation treatment.

PMID- 11835655
TI  - Intracoronary radiation: are the frequent flyers still around?

PMID- 11835656
TI  - A case of acute myocardial infarction treated with a new thrombectomy system.
AB  - Thrombotic occlusion in the culprit lesion of acute myocardial infarction was
      successfully recanalized using a 4.5 Fr thrombectomy catheter (RESCUE), which was
      also used to normalize the coronary blood flow. The retrieved specimens were
      white thrombi containing red thrombi and cholesterol crystals, indicating plaque
      rupture.

PMID- 11835657
TI  - Mechanical thrombectomy to the RESCUE.

PMID- 11835658
TI  - Severe intravascular hemolysis after transcatheter closure of a large patent
      ductus arteriosus using the Amplatzer duct occluder: successful resolution by
      intradevice coil deployment.
AB  - A 21-year-old female developed severe unremitting intravascular hemolysis
      following closure of a large patent ductus arteriosus using an Amplatzer duct
      occluder. Percutaneous deployment of fibered platinum coils within the nitinol
      wire cage of the Amplatzer duct occluder abolished the residual shunt through the
      device and resulted in cessation of intravascular hemolysis and reversal of its
      adverse sequelae.

PMID- 11835659
TI  - Prevention of distal embolization following the treatment of late stent
      occlusion.
AB  - We report the use of the AngioGard system in the treatment of acute, late in
      stent occlusion of the circumflex coronary artery. This case shows that late
      stent occlusion can in part be due to in-stent thrombosis and the use of an
      embolization protection device should be considered in this context.

PMID- 11835660
TI  - Management of intracoronary thrombus in 2002.

PMID- 11835662
TI  - Flow wire fouls pressure wire: red card for both.

PMID- 11835661
TI  - Simultaneous intracoronary pressure and Doppler guidewires to assess coronary
      stenosis: if one is enough, are two too much?
AB  - We report a potential source of erroneous estimation of stenosis severity by
      pressure guidewire assessment. Simultaneous introduction of pressure and Doppler
      guidewires can lead to an overestimation of stenosis pressure gradient in the
      evaluation of intermediate stenosis.

PMID- 11835663
TI  - Intracoronary retrieval of the dehisced radiopaque ring of a guiding catheter: an
      unusual complication of coronary angioplasty.
AB  - The guiding catheter used in coronary intervention may be damaged or some parts
      could be dehisced during the procedure, producing adverse effects in the vascular
      tree. So much so that immediate surgery is usually indicated. We report a case
      with a dehisced radiopaque ring of the catheter during the procedure. It was
      retrieved percutaneously without thoracotomy.

PMID- 11835664
TI  - Coronary restenosis: a review of current insights and therapies.

PMID- 11835665
TI  - Is it just the money?

PMID- 11835668
TI  - Successful targeting of mouse Y chromosome genes using a site-directed insertion
      vector.
AB  - Gene targeting via homologous recombination in mouse ES cells is now a routine
      method for addressing gene function in vivo. Several hundred genes mapping to all
      autosomes and the X chromosome have been mutated and analyzed in this way. In
      contrast, despite repeated attempts in several laboratories, including our own,
      there have been no reports of successful targeting of mouse Y chromosome genes.
      We show here that this problem can be overcome through the use of insertional
      targeting, rather than the usual replacement strategy. Using this method we have
      successfully targeted the mouse Y located Dby (dead box Y) and Eif2s3y
      (elongation initiation factor) genes. In addition, as Y chromosome genes are
      transcribed in ES cells, successful targeting and disruption of gene expression
      can be easily confirmed by RTPCR analysis of selected clones.

PMID- 11835669
TI  - A Cre recombinase transgene with mosaic, widespread tamoxifen-inducible action.
AB  - Cre-mediated site-specific recombination allows conditional transgene expression
      or gene knockouts in mice. Inducible Cre recombination systems have been
      developed to bypass initial embryonic lethal phenotypes and provide access to
      later embryonic or adult phenotypes. We have produced Cre transgenic mice in
      which excision is tamoxifen inducible and occurs in a widespread mosaic pattern.
      We utilized our Cre excision reporter system combined with an embryonic stem (ES)
      cell screen to identify ES cell clones with undetectable background Cre activity
      in the absence of tamoxifen but efficient excision upon addition of tamoxifen.
      The CreER transgenic mouse lines derived from the ES cells were tested using the
      Z/AP and Z/EG Cre reporter lines. Reporter gene expression indicated Cre excision
      was maximal in midgestation embryos by 2 days after tamoxifen administration,
      with an overall efficiency of 5-10% of cells with Cre excision. At 3 days after
      tamoxifen treatment most reporter gene expression marked groups of cells,
      suggesting an expansion of cells with Cre excision, and the proportion of cells
      with Cre excision was maintained. In adults, Cre excision was also observed with
      varying efficiencies in all tissues after tamoxifen treatment.

PMID- 11835670
TI  - Codon-improved Cre recombinase (iCre) expression in the mouse.
AB  - By applying the mammalian codon usage to Cre recombinase, we improved Cre
      expression, as determined by immunoblot and functional analysis, in three
      different mammalian cell lines. The improved Cre (iCre) gene was also designed to
      reduce the high CpG content of the prokaryotic coding sequence, thereby reducing
      the chances of epigenetic silencing in mammals. Transgenic iCre expressing mice
      were obtained with good frequency, and in these mice loxP-mediated DNA
      recombination was observed in all cells expressing iCre. Moreover, iCre fused to
      two estrogen receptor hormone binding domains for temporal control of Cre
      activity could also be expressed in transgenic mice. However, Cre induction after
      administration of tamoxifen yielded only low Cre activity. Thus, whereas
      efficient activation of Cre fusion proteins in the brain needs further
      improvements, our studies indicate that iCre should facilitate genetic
      experiments in the mouse.

PMID- 11835671
TI  - High-efficiency gene transfer into adult fish: a new tool to study fin
      regeneration.
AB  - Zebrafish represents an excellent model to study the function of vertebrate genes
      (e.g., well-developed genetics, large number of mutants, and genomic sequencing
      in progress), inasmuch as we have tools to manipulate gene expression. Recent use
      of injected morpholinos in eggs provides a good method to " knockdown " gene
      expression in early development (Nasevicius and Ekker, 2000), and the "caged" RNA
      injected in eggs allows to overexpress a gene in a specific set of cells (Ando et
      al., 2001). However, a method to specifically modify gene expression in the
      juvenile or in the adult is still missing. Such a method would be a very powerful
      tool to understand gene function in differentiated tissues. We describe here an
      electroporation-based approach, which allows gene transfer in adult tissues. Its
      efficiency was assessed using a GFP (green fluorescent protein) dependent assay.
      We then used this method to disrupt the Fgf signalling pathway during the process
      of regeneration.

PMID- 11835672
TI  - The cerebellar deficient folia (cdf) gene acts intrinsically in Purkinje cell
      migrations.
AB  - Cerebellar deficient folia (cdf) is a recently identified mouse mutation causing
      ataxia and cerebellar abnormalities including lobulation defects and abnormal
      placement of a specific subset of Purkinje cells. To understand the etiology of
      the cerebellar defects in cdf mutant mice, we examined postnatal development of
      the cdf/cdf cerebellum. Our results demonstrate that Purkinje cell ectopia and
      foliation defects are apparent at birth, suggesting the cdf mutation disrupts the
      positioning of many, but not all, Purkinje cells during development. In addition
      to cerebellar abnormalities, we observed lamination defects in the hippocampus of
      cdf mutant mice, although neocortical defects were not seen. Furthermore, ectopic
      Purkinje cells in cdf/cdf mice express an increased level of Dab1 protein, as
      previously observed in mice with mutations in genes in the reelin signaling
      pathway. Lastly, analysis of cdf <-->ROSA26 chimeric mice demonstrated that the
      cdf mutation is intrinsic to Purkinje cells. We suggest that the cdf gene product
      is required in a subset of Purkinje cells, possibly to respond to Reelin signals.

PMID- 11835673
TI  - What's buzzing? Mosquito genomics and transgenic mosquitoes.
AB  - Genome projects and associated technologies are now being established for
      mosquito species that are vectors of human disease. The recent announcement of an
      award by the National Institute of Allergy and Infectious Diseases (NIAID) to
      Celera Genomics to sequence the Anopheles gambiae genome will further accelerate
      the completion of the sequencing of this genome. Completion of the An. gambiae
      sequence will mean that the genomes of all three organisms involved in the
      transmission of falciparum malaria--the mosquito, the parasite, and the human-
      will have been sequenced. This will greatly facilitate the identification of
      genes and pathways involved in the transmission of malaria. The recent genetic
      transformation of An. gambiae with the piggyBac transposable element and the
      transformation of another important malarial vector, Anopheles stephensi using
      the Minos element, now provide researchers with powerful tools with which to
      genetically manipulate these medically important vector species. Here we review
      the recent progress made in the extension of contemporary tools of modern
      genetics and genomics into these medically important insects.

PMID- 11835674
TI  - EPR dosimetric properties of 2-methylalanine: EPR, ENDOR and FT-EPR
      investigations.
AB  - To find an EPR dosimeter material that is sensitive enough for clinical use, the
      substance 2-methylalanine (2MA) with the chemical structure
      (CH(3))(2)C(NH(3)(+))COO(-) was tested for its sensitivity to ionizing radiation,
      dose response, and radical stability over time. At equal and moderate settings of
      microwave power and modulation amplitude, 2MA was found to be 70% more sensitive
      than L-alpha-alanine, which is the most common EPR dosimeter material today. The
      dose response is linear, at least in the dose range of interest (0.5-00 Gy), and
      the time-dependent variations in signal intensity are very small and may be
      corrected for easily. The energy dependence of the stopping power and energy
      absorption was calculated and was found to be similar to that of alanine. The
      dependence of the signal intensity on microwave power and modulation amplitude
      was investigated, and the optimal settings were found to be 25 mW (Bruker ER
      4102ST) and 12 gauss, respectively. Single crystals of 2MA were analyzed using
      ENDOR and ENDOR-induced EPR to identify the radiation-induced radicals that
      formed. Only one radical, in which the amino group is detached from the original
      molecule, was identified. This radical is obviously dominating and is apparently
      the only one relevant for dosimetry purposes. The complete set of coupling
      parameters for three hyperfine couplings is reported. The power saturation
      properties and spectral line width are ruled by the relaxation times T(1) and
      T(2). To determine the relaxation times of 2MA, pulsed EPR experiments were
      performed on single crystals. Two different values of T(1) were obtained, one in
      the range 1-3 micros, shown to be of importance for the dosimetry properties, and
      another that is strongly anisotropic with a value between 10 and 35 micros that
      does not seem to affect the saturation behavior. T(2) was estimated to be of the
      order of 200-300 ns.

PMID- 11835675
TI  - The kinetics of radiation damage to the protein luciferase and recovery of enzyme
      activity after irradiation.
AB  - Experimental observations are reported which follow the bioluminescence intensity
      of luciferase during irradiation by a 5 MeV proton beam. Bioluminescence is a
      measure of the protein enzyme activity and provides an assay of the enzyme rate
      of reaction in real time. Transient responses after a pulse of protons show
      recovery of the reaction rate with two time constants of 0.3 s(-1) and 0.01 s(
      1). Changes in the reaction rate are due to radiation damage to the active form
      of the protein luciferase. Quantitative analysis of the radiation damage and
      recovery of the protein shows that products of the radiolysis of water play major
      part in the process of enzyme damage at room temperature. A few minutes after the
      pulse of protons, most of the enzyme activity has recovered. We attribute the
      fast recovery to the removal of charged ions, while the slow recovery involves
      refolding of denatured protein.

PMID- 11835676
TI  - Cell inactivation and double-strand breaks: the role of core ionizations, as
      probed by ultrasoft X rays.
AB  - The large RBE (approximately 7) measured for the killing of Chinese hamster V79
      cells by 340 eV ultrasoft X rays, which preferentially ionize the K shell of
      carbon atoms (Herve du Penhoat et al., Radiat. Res. 151, 649-658, 1999), was used
      to investigate the location of sensitive sites for cell inactivation and the
      physical modes of action of radiation. The enhancement of the RBE above the
      carbon K-shell edge either may indicate a high intrinsic efficiency of carbon K
      shell ionizations (due, for example, to a specific physical or chemical effect)
      or may be related to the preferential localization of these ionizations on the
      DNA. The second interpretation would indicate a strong local (within 3 nm) action
      of K-shell ionizations and consequently the importance of a direct mechanism for
      radiation lethality (without excluding an action in conjunction with an indirect
      component). To distinguish between these two hypotheses, the efficiencies of core
      ionizations in DNA atoms (phosphorus L-shell, carbon K-shell, and oxygen K-shell
      ionizations) to induce damages were investigated by measuring their capacities to
      produce DNA double-strand breaks (DSBs). The effect of photoionizations in
      isolated DNA was studied using pBS plasmids in a partially hydrated state. No
      enhancement of the efficiency of DSB induction by carbon K-shell ionizations
      compared to oxygen K-shell ionizations was found, supporting the hypothesis that
      it is the localization of these carbon K-shell events on DNA which gives to the
      340 eV photons their high killing efficiency. In agreement with this
      interpretation, cell inactivation and DSB induction, which do not appear to be
      correlated when expressed in terms of yields per unit dose in the sample, exhibit
      a rather good correlation when expressed in terms of efficiencies per core event
      in the DNA. These results suggest that core ionizations in DNA, through core-hole
      relaxation in conjunction with localized effects of spatially correlated
      secondary and Auger electrons, may be the major critical events for cell
      inactivation, and that the resulting DSBs (or a constant fraction of these DSBs)
      may be a major class of unrepairable lesions.

PMID- 11835677
TI  - Heavy ion-induced DNA double-strand breaks in yeast.
AB  - Induction of DSBs in the diploid yeast, Saccharomyces cerevisiae, was measured by
      pulsed-field gel electrophoresis (PFGE) after the cells had been exposed on
      membrane filters to a variety of energetic heavy ions with values of linear
      energy transfer (LET) ranging from about 2 to 11,500 keV/microm, (241)Am alpha
      particles, and 80 keV X rays. After irradiation, the cells were lysed, and the
      chromosomes were separated by PFGE. The gels were stained with ethidium bromide,
      placed on a UV transilluminator, and analyzed using a computer-coupled camera.
      The fluorescence intensities of the larger bands were found to decrease
      exponentially with dose or particle fluence. The slope of this line corresponds
      to the cross section for at least one double-strand break (DSB), but closely
      spaced multiple breaks cannot be discriminated. Based on the known size of the
      native DNA molecules, breakage cross sections per base pair were calculated. They
      increased with LET until they reached a transient plateau value of about 6 x 10(
      7) microm(2) at about 300-2000 keV/microm; they then rose for the higher LETs,
      probably reflecting the influence of delta electrons. The relative biological
      effectiveness for DNA breakage displays a maximum of about 2.5 around 100-200
      keV/microm and falls below unity for LET values above 10(3) keV/microm. For these
      yeast cells, comparison of the derived breakage cross sections with the
      corresponding cross section for inactivation derived from the terminal slope of
      the survival curves shows a strong linear relationship between these cross
      sections, extending over several orders of magnitude.

PMID- 11835678
TI  - Potentiation of cell killing by low-dose-rate radiation by camptothecin is
      related to an increase in the level of DNA double-strand breaks.
AB  - We investigated the ability of camptothecin to potentiate cell killing by low
      dose-rate irradiation and whether this potentiation was associated with an
      increase in the level of residual DNA double-strand breaks (DSBs). Human melanoma
      (Sk-Mel-3) cells, grown to the confluent phase, were treated with low-dose-rate
      radiation (0.88 cGy/min) alone, camptothecin alone, or concurrent camptothecin
      and low-dose-rate radiation. Cell survival was determined using a clonogenic
      assay. The interactions between camptothecin and low-dose-rate radiation were
      analyzed further using isobolograms. DNA DSBs were determined using the neutral
      comet assay. We found that 10 and 25 microM camptothecin, but not 1 microM,
      camptothecin potentiated cell killing significantly relative to that seen with
      low-dose-rate radiation alone. Unexpectedly, the potentiation of the effects of
      low-dose-rate radiation by camptothecin was accompanied by large increases in the
      alpha parameter of the linear-quadratic fit rather than in the beta parameter.
      This suggests a modification of intrinsic radiosensitivity rather than of repair
      of sublethal damage. From isobologram analysis, low-dose-rate radiation
      interacted either additively or supra-additively with 25 or 10 microM
      camptothecin. Conversely, the interaction of low-dose-rate radiation with 1
      microM camptothecin was subadditive. Finally, there were strong correlations
      (correlation coefficients >0.9) between surviving fraction and either comet tail
      length or comet tail moment after concurrent treatment with 25 microM
      camptothecin and low-dose-rate radiation. This suggests that the level of
      residual DNA DSBs was a good indicator of cell killing after treatment with low
      dose-rate radiation plus 25 microM camptothecin.

PMID- 11835679
TI  - Delayed chromosome changes in gamma-irradiated normal and Li-Fraumeni
      fibroblasts.
AB  - Knockout mice with only one Trp53 allele (+/- genotype) are highly susceptible to
      radiation-induced cancers, possibly through numerical chromosome changes.
      Patients with the Li-Fraumeni syndrome, having heterozygous TP53 germline
      mutations (+/mut genotype), are also susceptible to spontaneous and radiogenic
      cancers. We have investigated the susceptibility of six Li-Fraumeni syndrome
      +/mut and six normal fibroblast strains to induced numerical and unstable
      structural aberrations at six population doublings after exposure to 3 or 6 Gy
      gamma rays. Four of the irradiated Li-Fraumeni syndrome strains showed small
      increases in both aberration types, similar to those seen in the normal strains.
      In two irradiated Li-Fraumeni syndrome strains, there were high levels of induced
      structural changes, and one of these showed a modest increase in hyperploidy. We
      suggest that enhanced sensitivity to delayed radiation-induced chromosome changes
      in Li-Fraumeni syndrome cells requires other genetic alterations in addition to
      TP53 heterozygosity, apparently in contrast to the situation in Trp53
      heterozygous null mice. If such additional alterations occur in vivo in Li
      Fraumeni syndrome patients, they may predispose them to radiogenic cancers,
      mainly through enhanced structural rather than numerical chromosome changes. Our
      findings raise questions about the validity of quantitative extrapolation of
      cytogenetic data from Trp53-defective mice to radiogenic cancer risk in humans.

PMID- 11835680
TI  - Caffeine induces TP53-independent G(1)-phase arrest and apoptosis in human lung
      tumor cells in a dose-dependent manner.
AB  - Caffeine is a model radiosensitizing agent that is thought to work by abrogating
      the radiation-induced G(2)-phase checkpoint. In this study, we examined the
      effect that various concentrations of caffeine had on cell cycle checkpoints and
      apoptosis in cells of a human lung carcinoma cell line and found that a
      concentration of 0.5 mM caffeine could abrogate the G(2)-phase arrest normally
      seen after exposure to ionizing radiation. Surprisingly, at a concentration of 5
      mM, caffeine not only induced apoptosis by itself and acted synergistically to
      enhance radiation-induced apoptosis, but also induced a TP53-independent G(1)
      phase arrest. Examination of the molecular mechanisms by which caffeine produced
      these effects revealed that caffeine had opposing effects on different cyclin
      dependent kinases. CDK2 activity was suppressed by caffeine, whereas activity of
      CDC2 was enhanced by suppressing phosphorylation on Tyr15 and by interfering with
      14-3-3 binding to CDC25C. These data indicate that the effect of caffeine on cell
      cycle checkpoints and apoptosis is dependent on dose and that caffeine acts
      through differential regulation of cyclin-dependent kinase activity.

PMID- 11835681
TI  - Tissue Raman spectroscopy for the study of radiation damage: brain irradiation of
      mice.
AB  - Radiotherapy is routinely employed in the treatment of head and neck cancers.
      Acute cell death, radiation-activated chemical cascades, and the induction of
      genes coding for protective factors like cytokines are considered to be the major
      processes involved in radiation damage and repair. It should be possible to
      follow these processes by monitoring the biochemical interactions initiated by
      radiation. We have carried out Raman spectroscopy studies on tissue from mice
      subjected to brain irradiation to identify the biochemical changes occurring in
      tissue and brain as a result of radiation injury. These studies show that brain
      irradiation produces drastic spectral changes even in tissue far removed from the
      irradiation site. The changes are very similar to those produced by the stress of
      inoculation and restraint and the administration of an anesthetic drug. While the
      changes produced by stress or anesthetics last for only a short time (a few hours
      to 1 or 2 days), radiation-induced changes persist even after 1 week. The
      spectral changes can be interpreted in terms of the observation of new spectra
      that are dominated by bands due to proteins. The results thus support the
      hypothesis that various protective factors are released throughout the body when
      the central nervous system (CNS) is exposed to radiation.

PMID- 11835682
TI  - Chronic exposure to a GSM-like signal (mobile phone) does not stimulate the
      development of DMBA-induced mammary tumors in rats: results of three consecutive
      studies.
AB  - Certain epidemiological and experimental studies raised concerns about the safety
      of radiofrequency (RF) electromagnetic fields because of a possible increased
      risk of leukemia and lymphoma. In this study, an RF field used in mobile
      telecommunication was tested using 7,12-dimethylbenz[a]anthracene (DMBA)-induced
      mammary tumors in female Sprague-Dawley rats as a model for human breast cancer.
      Three experiments were carried out under strictly standardized conditions and
      were started on the same day of three consecutive years. The field consisted of a
      GSM-like signal (900 MHz pulsed at 217 Hz, pulse width 577 micros) of relatively
      low power flux density (100 microW/cm(2) +/- 3 dB) and was applied continuously
      throughout each experiment to freely moving animals. The specific absorption
      rates averaged over the whole body were 17.5-70 mW/kg. The highest values in
      young animals were at or around the exposure limit permissible for the general
      public (i.e. 80 mW/kg). The animals were palpated weekly for the presence of
      mammary tumors and were killed humanely when tumors reached a diameter of 1-2 cm
      to allow a reliable histopathological classification and a distinction between
      malignant and benign subtypes. The overall results of the three studies are that
      there was no statistically significant effect of RF-field exposure on tumor
      latency and that the cumulative tumor incidence at the end of the experiment was
      unaffected as well. The risk ratios were 1.08 (95% CI: 0.91-1.29) and 0.96 (95%
      CI: 0.85-1.07) for benign and malignant tumors, respectively. These observations
      are in agreement with other published findings. In the first experiment, however,
      the median latency for the development of the first malignant tumor in each
      animal was statistically significantly extended for RF-field-exposed animals
      compared to controls (278 days compared to 145 days, P = 0.009). No such
      differences were detected in the two subsequent experiments. These results show
      that low-level RF radiation does not appear to possess carcinogenic or cancer
      promoting effects on DMBA-induced mammary tumors. To explain the mechanisms
      underlying the different results obtained in the three experiments, a hypothesis
      is presented which is based upon the neuroendocrine control mechanisms involved
      in the promotion of DMBA-induced mammary tumors. Despite the apparent absence of
      stimulatory effects of low-level RF-field exposure on the development and growth
      of solid tumors, it will be necessary to verify these results for leukemias and
      lymphomas, which may have completely different biological control mechanisms.

PMID- 11835683
TI  - Role of CD13/aminopeptidase N in rat lymphocytic alveolitis caused by thoracic
      irradiation.
AB  - CD13/aminopeptidase N is a cell surface glycoprotein that is widely distributed
      in a variety of mammalian cells. It was recently shown to have chemotactic
      activity for T lymphocytes. This study examined the role of CD13/aminopeptidase N
      in lymphocytic alveolitis in radiation-induced lung injury caused by a single
      dose thoracic irradiation (15 Gy) in rats. Significantly increased aminopeptidase
      activity was detected in bronchoalveolar lavage fluid obtained from irradiated
      rats at 4 weeks after irradiation compared to the activity in unirradiated rats.
      Significantly higher aminopeptidase activity was detected on alveolar macrophages
      from irradiated rats at 2 and 4 weeks than on those from unirradiated rats.
      Western blot analysis showed an increased expression of CD13/aminopeptidase N
      protein in alveolar macrophages from irradiated rats at 4 weeks. Chemotactic
      activity for normal rat lymphocytes was detected in bronchoalveolar lavage fluid
      from irradiated rats at 4 weeks, and approximately 60% of the activity was
      inhibited by pretreatment of bronchoalveolar lavage fluid with bestatin, a
      specific aminopeptidase inhibitor. This study suggests that CD13/aminopeptidase N
      may play an important role as a lymphocyte chemoattractant in lymphocyte-mediated
      alveolitis in experimental radiation-induced lung injury.

PMID- 11835684
TI  - Retinoic acid exacerbates experimental radiation nephropathy.
AB  - Studies have shown that angiotensin-converting enzyme inhibitors and an
      angiotensin II receptor blocker can delay, but cannot reverse, the progression of
      experimentally induced radiation nephropathy. In an effort to find a method for
      reversing injury, three agents were tested in a rat model of radiation
      nephropathy. Pirfenidone (a phenyl-pyridone antifibrotic) and thiaproline (an
      inhibitor of collagen deposition) were not capable of retarding the development
      of radiation nephropathy. However, all-trans retinoic acid (an anti-inflammatory
      agent) exacerbated radiation nephropathy. We speculated that the detrimental
      effects of retinoic acid might be the result of stimulation of renal cell
      proliferation. However, retinoic acid had no effect on tubular or glomerular cell
      proliferation in normal animals and did not enhance radiation-induced
      proliferation. A recent report that retinoic acids inhibit nitric oxide
      production suggested an alternative mechanism, since inhibition of production of
      nitric oxide is known to exacerbate radiation nephropathy. Experiments
      demonstrated that retinoic acid exacerbated the radiation-induced drop in renal
      production of nitric oxide, suggesting that the detrimental effect of all-trans
      retinoic acid might be explained by inhibition of renal nitric oxide activity.
      Particularly in view of the recent clinical report of enhancement of radiation
      nephropathy by retinoic acid in patients receiving bone marrow transplantation,
      the combination of retinoic acid and renal irradiation should be carried out with
      great caution.

PMID- 11835685
TI  - Modifying normal tissue damage postirradiation. Report of a workshop sponsored by
      the Radiation Research Program, National Cancer Institute, Bethesda, Maryland,
      September 6-8, 2000.
AB  - Late effects that develop in normal tissues adjacent to the tumor site in the
      months to years after radiotherapy can reduce the quality of life of cancer
      survivors. They can be dose-limiting and debilitating or life-threatening. There
      is now evidence that some late effects may be preventable or partially
      reversible. A workshop, "Modifying Normal Tissue Damage Postirradiation", was
      sponsored by the Radiation Research Program of the National Cancer Institute to
      identify the current status of and research needs and opportunities in this area.
      Mechanistic, genetic and physiological studies of the development of late effects
      are needed and will provide a rational basis for development of treatments.
      Interdisciplinary teams will be needed to carry out this research, including
      pathologists, physiologists, geneticists, molecular biologists, experts in
      functional imaging, wound healing, burn injury, molecular biology, and medical
      oncology, in addition to radiation biologists, physicists and oncologists. The
      participants emphasized the need for developing and choosing appropriate models,
      and for radiation dose-response studies to determine whether interventions remain
      effective at the radiation doses used clinically. Both preclinical and clinical
      studies require long-term follow-up, and easier-to-use, more objective clinical
      scoring systems must be developed and standardized. New developments in
      biomedical imaging should provide useful tools in all these endeavors. The
      ultimate goals are to improve the quality of life and efficacy of treatment for
      cancer patients treated with radiotherapy.

PMID- 11835687
TI  - Match-only integral distribution (MOID) algorithm for high-density
      oligonucleotide array analysis.
AB  - BACKGROUND: High-density oligonucleotide arrays have become a valuable tool for
      high-throughput gene expression profiling. Increasing the array information
      density and improving the analysis algorithms are two important computational
      research topics. RESULTS: A new algorithm, Match-Only Integral Distribution
      (MOID), was developed to analyze high-density oligonucleotide arrays. Using known
      data from both spiking experiments and no-change experiments performed with
      Affymetrix GeneChip arrays, MOID and the Affymetrix algorithm implemented in
      Microarray Suite 4.0 (MAS4) were compared. While MOID gave similar performance to
      MAS4 in the spiking experiments, better performance was observed in the no-change
      experiments.MOID also provides a set of alternative statistical analysis tools to
      MAS4. There are two main features that distinguish MOID from MAS4. First, MOID
      uses continuous P values for the likelihood of gene presence, while MAS4 resorts
      to discrete absolute calls. Secondly, MOID uses heuristic confidence intervals
      for both gene expression levels and fold change values, while MAS4 categorizes
      the significance of gene expression level changes into discrete fold change
      calls. CONCLUSIONS: The results show that by using MOID, Affymetrix GeneChip
      arrays may need as little as ten probes per gene without compromising analysis
      accuracy.

PMID- 11835688
TI  - Evidence for an evolutionarily conserved interaction between cell wall
      biosynthesis and flowering in maize and sorghum.
AB  - BACKGROUND: Factors that affect flowering vary among different plant species, and
      in the grasses in particular the exact mechanism behind this transition is not
      fully understood. The brown midrib (bm) mutants of maize (Zea mays L.), which
      have altered cell wall composition, have different flowering dynamics compared to
      their wild-type counterparts. This is indicative of a link between cell wall
      biogenesis and flowering. In order to test whether this relationship also exists
      in other grasses, the flowering dynamics in sorghum (Sorghum bicolor (L.) Moench)
      were investigated. Sorghum is evolutionarily closely related to maize, and a set
      of brown midrib (bmr) mutants similar to the maize bm mutants is available,
      making sorghum a suitable choice for study in this context. RESULTS: We compared
      the flowering time (time to half-bloom) of several different bmr sorghum lines
      and their wild-type counterparts. This revealed that the relationship between
      cell wall composition and flowering was conserved in sorghum. Specifically, the
      mutant bmr7 flowered significantly earlier than the corresponding wild-type
      control, whereas the mutants bmr2, bmr4, bmr6, bmr12, and bmr19 flowered later
      than their wild-type controls. CONCLUSION: The change in flowering dynamics in
      several of the brown midrib sorghum lines provides evidence for an evolutionarily
      conserved mechanism that links cell wall biosynthesis to flowering dynamics. The
      availability of the sorghum bmr mutants expands the germplasm available to
      investigate this relationship in further detail.

PMID- 11835689
TI  - Phorbol esters and cAMP differentially regulate the expression of CD4 and CD8 in
      human thymocytes.
AB  - BACKGROUND: Intrathymic development and selection of the T lymphocyte repertoire
      is restricted by the interactions of the T cell antigen receptor and CD4 or CD8
      co-receptors with self major histocompatibility complex molecules. Positive or
      negative selection depends on a tight regulatory control of CD4 and CD8
      expression. Determining the intracellular signals that differentially regulate
      the expression of CD4 and CD8 is important to understand the mechanisms that are
      implicated in selection of single positive CD4+CD8- or CD4-CD8+. RESULTS: The
      present study shows that stimulation of human thymocytes by phorbol esters or
      cAMP result in a differential regulation of CD4 and CD8 expression, both at the
      mRNA and cell surface glycoprotein level. CONCLUSIONS: The differential
      regulation of CD4 and CD8 gene expression suggests that the selective activation
      of protein kinase C (PKC) and cAMP-dependent protein kinases (PKA) may be
      required for the selection of single positive CD4+CD8- and CD4-CD8+ cells during
      Intrathymic differentiation.

PMID- 11835690
TI  - Pharmacokinetics of artesunate after single oral administration to rats.
AB  - BACKGROUND: Artesunate is a commonly used antimalarial drug derived from
      artemisinin. It is rapidly converted to dihydroartemisinin. Little is known on
      this conversion in the GI tract and blood, and how this influences absorption. In
      order to study the absorption phase of the kinetics of artesunate following oral
      administration in rats, samples were collected at baseline, and then 0.5, 2, 5,
      10, 15, 30, 45, 60 and 120 minutes after a single dose of 150 mg. RESULTS: Peak
      concentration of parent artesunate and dihydroartemisinin was achieved within 5
      and 37.5 +/- 8.7 min, respectively of start of administration through gavage. The
      half lives of absorption were 2.73 +/- 0.85 and 12.49 +/- 2.49 min, respectively.
      CONCLUSIONS: These times were considerably shorter for artesunate than those
      found in studies which start sampling later. The profiles of parent compound and
      metabolite result from a complex equation dictated by the pH-dependent rates of
      hydroxylation of artesunate to dihydroartemisinin, the different rates at which
      either compounds are absorbed, and the catalytic hydroxylation by esterases. The
      rate of chemical oxidation of artesunate is pH dependent; this explains its rapid
      conversion to dihydroartemisinin in the stomach, as compared to its greater
      stability in other compartments at higher pH and in plasma. We propose that
      variable proportions of absorption take place in the stomach, and conclude that
      parent artesunate reaches an early peak within minutes of dosing, and that the
      early dihydroartemisinin levels result primarily from the absorption of the
      metabolite as such.

PMID- 11835691
TI  - Angiotensin II induced inflammation in the kidney and in the heart of double
      transgenic rats.
AB  - BACKGROUND: We are investigating a double transgenic rat (dTGR) model, in which
      rats transgenic for the human angiotensinogen and renin genes are crossed. These
      rats develop moderately severe hypertension but die of end-organ cardiac and
      renal damage by week 7. The heart shows necrosis and fibrosis, whereas the
      kidneys resemble the hemolytic-uremic syndrome vasculopathy. Surface adhesion
      molecules (ICAM-1 and VCAM-1) are expressed early on the endothelium, while the
      corresponding ligands are found on circulating leukocytes. Leukocyte infiltration
      in the vascular wall accompanies PAI-1, MCP-1, iNOS and Tissue Factor expression.
      Furthermore we show evidence that Ang II causes the upregulation of NF-kB in our
      model. METHODS: We started PDTC-treatment on four weeks old dTGR (200 mg/kg sc)
      and age-matched SD rats. Blood-pressure- and albuminuria- measurements were
      monitored during the treatment period (four weeks). The seven weeks old animals
      were killed, hearts and kidneys were isolated and used for immunohistochemical
      and electromobility shift assay analysis. RESULTS: Chronic treatment with the
      antioxidant PDTC decreased blood pressure (162 plus minus 8 vs. 190 plus minus 7
      mm Hg, p = 0.02). Cardiac hypertrophy index was significantly reduced (4.90 plus
      minus 0.1 vs. 5.77 plus minus 0.1 mg/g, p < 0.001) compared to dTGR. PDTC reduced
      24 h albuminuria by 85 % (2.7 plus minus 0.5 vs. 18.0 plus minus 3.4 mg/d, p <
      0.001) and prevented death significantly. Vascular injury was ameliorated in
      small renal and cardiac vessels. PDTC inhibited NF-kappaB binding activity in
      heart and kidney. Immunohistochemical analysis shows increased expression of the
      p65 NF-kappaB subunit in the endothelium, smooth muscles cells of damaged small
      vessels, infiltrated cells, glomeruli, tubuli and collecting ducts of dTGR. PDTC
      markedly reduced the immunoreactivity of p65. CONCLUSION: Our data show that
      inhibition of NF-kappaB by PDTC markedly reduces inflammation, iNOS expression in
      the dTGR most likely leading to decreased cytotoxicity, and cell proliferation.
      Thus, NF-kappaB activation plays an important role in ANG II-induced end-organ
      damage.

PMID- 11835692
TI  - Design and performance of a multi-centre randomised controlled trial and economic
      evaluation of joint tele-consultations [ISRCTN54264250].
AB  - BACKGROUND: Appropriate information flow is crucial to the care of patients,
      particularly at the interface between primary and secondary care. Communication
      problems can result from inadequate organisation and training, There is a major
      expectation that information and communication technologies may offer solutions,
      but little reliable evidence. This paper reports the design and performance of a
      multi-centre randomised controlled trial (RCT), unparalleled in telemedicine
      research in either scale or range of outcomes. The study investigated the
      effectiveness and cost implications in rural and inner-city settings of using
      videoconferencing to perform joint tele-consultations as an alternative to
      general practitioner referral to the hospital specialist in the outpatient
      clinic. METHODS: Joint tele-consultation services were established in both the
      Royal Free Hampstead NHS Trust in inner London, and the Royal Shrewsbury
      Hospitals Trust, in Shropshire. All the patients who gave consent to participate
      were randomised either to joint tele-consultation or to a routine outpatients
      appointment. The principal outcome measures included the frequency of decision by
      the specialist to offer a follow-up outpatient appointment, patient satisfaction
      (Ware Specific Questionnaire), wellbeing (SF12) and enablement (PEI), numbers of
      tests, investigations, procedures and treatments. RESULTS: A total of 134 general
      practitioners operating from 29 practices participated in the trial, referring a
      total of 3170 patients to 20 specialists in ENT medicine, general medicine
      (including endocrinology, and rheumatology), gastroenterology, orthopaedics,
      neurology and urology. Of these, 2094 patients consented to participate in the
      study and were correctly randomised. There was a 91% response rate to the initial
      assessment questionnaires, and analysis showed equivalence for all key
      characteristics between the treatment and control groups. CONCLUSION: We have
      designed and performed a major multi-centre trial of teleconsultations in two
      contrasting centres. Many problems were overcome to enable the trial to be
      carried out, with a considerable development and learning phase. A lengthier
      development phase might have enabled us to improve the patient selection
      criteria, but there is a window of opportunity for these developments, and we
      believe that our approach was appropriate, allowing the evaluation of the
      technology before its widespread implementation.

PMID- 11835693
TI  - Utility of the Mayo End-Stage Liver Disease (MELD) score in assessing prognosis
      of patients with alcoholic hepatitis.
AB  - BACKGROUND: Alcoholic hepatitis is characterized by acute, or acute-on-chronic
      hepatic failure and associated with a high mortality. Specific therapies should
      be considered for those at high risk of mortality. The Mayo End-Stage Liver
      Disease (MELD) score is a marker of disease severity and mortality in persons
      with chronic alcoholic liver disease. Our aims were to assess the utility of the
      MELD score as a predictor of short-term mortality in persons with alcoholic
      hepatitis. METHODS: We assessed the utility of the MELD score and compared it
      with the Discriminant Function (DF) as a predictor of mortality in 34 patients
      hospitalized with alcoholic hepatitis. RESULTS: The area under the curve of a
      receiver operating characteristic curve for the MELD score was 0.82 (confidence
      intervals 0.65-0.98), and for the DF was 0.86 (confidence intervals 0.70-1.00).
      However, the sensitivity and specificity in predicting 30-day mortality for a
      MELD score of greater than 11 was 86% and 81%, but for a DF greater than 32 was
      86% and 48% respectively. The presence of ascites and bilirubin greater than 8
      mg/dL were also highly predictive of mortality with a sensitivity of 71% and a
      specificity of 96%. CONCLUSIONS: Alcoholic hepatitis remains associated with a
      high mortality in hospitalized patients. The MELD score performs as well as the
      DF in predicting mortality at 30 days. A MELD score of greater than 11, or the
      presence of both ascites and an elevated bilirubin greater than 8 mg/dL should
      prompt consideration of specific therapeutic interventions to reduce mortality.

PMID- 11835694
TI  - Prevalence and risk factors for vaginal Candida colonization in women with type 1
      and type 2 diabetes.
AB  - BACKGROUND: Diabetes mellitus increases the rate of vaginal colonization and
      infection with Candida species METHODS: We surveyed women with diabetes receiving
      care at either an urban or suburban diabetes clinic to examine the relationship
      between vaginal Candida colonization, diabetes type and duration, and HbA1c
      level. 101 participants completed the self-administered questionnaire and self
      collected a vaginal swab for Candida culture. Candida colonization was similar by
      age and race. RESULTS: Type 1 diabetics were three times as likely as type 2
      diabetics to be colonized with any Candida species (OR = 3.4; 95% CI: 1.03,
      11.41; p = 0.04); even after adjusting for abnormal HbA1c, which had an
      independent effect (OR = 1.4; 95% CI: 1.04, 1.76; p = 0.02). Recent antibiotic
      use (OR = 4.5; 95% CI: 1.18, 16.79; p = 0.03), lifetime history of chlamydia (OR
      = 5.8; 95% CI: 1.09, 30.54; p = 0.04), and performing oral sex during the past 2
      weeks (OR = 4.9; 95% CI:0.84, 28.27; p = 0.08) were also associated with Candida
      carriage after adjusting for diabetic type and abnormal HbA1c. C. albicans was
      isolated from the majority of colonized type 1 participants (56%), while C.
      glabrata was the most common isolate among colonized type 2 participants (54%).
      CONCLUSIONS: Improving glucose control and possibly modifying sexual behavior may
      reduce risk of Candida colonization, and potentially symptomatic infection, among
      women with diabetes.

PMID- 11835695
TI  - Subjective response to antipsychotic treatment and compliance in schizophrenia. A
      naturalistic study comparing olanzapine, risperidone and haloperidol (EFESO
      Study).
AB  - BACKGROUND: In order to compare the effectiveness of different antipsychotic
      drugs in the treatment of schizophrenia it is very important to evaluate
      subjective response and compliance in patient cohorts treated according to
      routine clinical practice. METHOD: Outpatients with schizophrenia entered this
      prospective, naturalistic study when they received a new prescription for an
      antipsychotic drug. Treatment assignment was based on purely clinical criteria,
      as the study did not include any experimental intervention. Patients treated with
      olanzapine, risperidone or haloperidol were included in the analysis. Subjective
      response was measured using the 10-item version of the Drug Attitude Inventory
      (DAI-10), and treatment compliance was measured using a physician-rated 4 point
      categorical scale. RESULTS: A total of 2128 patients initiated treatment (as
      monotherapy) with olanzapine, 417 with risperidone, and 112 with haloperidol.
      Olanzapine-treated patients had significantly higher DAI-10 scores and
      significantly better treatment compliance compared to both risperidone- and
      haloperidol-treated patients. Risperidone-treated patients had a significantly
      higher DAI-10 score compared to haloperidol-treated patients. CONCLUSION:
      Subjective response and compliance were superior in olanzapine-treated patients,
      compared to patients treated with risperidone and haloperidol, in routine
      clinical practice. Differences in subjective response were explained largely, but
      not completely, by differences in incidence of EPS.

PMID- 11835696
TI  - Characterization of a protease produced by a Trichoderma harzianum isolate which
      controls cocoa plant witches' broom disease.
AB  - BACKGROUND: Several Trichoderma strains have been reported to be effective in
      controlling plant diseases, and the action of fungal hydrolytic enzymes has been
      considered as the main mechanism involved in the antagonistic process. However,
      although Trichoderma strains were found to impair development of Crinipellis
      perniciosa, the causal agent of cocoa plant witches' broom disease, no fungal
      strain is available for effective control of this disease. We have then
      undertaken a program of construction of hydrolytic enzyme-overproducing
      Trichoderma strains aiming improvement of the fungal antagonistic capacity. The
      protease of an indian Trichoderma isolate showing antagonistic activity against
      C. perniciosa was purified to homogeneity and characterized for its kinetic
      properties and action on the phytopathogen cell wall. RESULTS: A protease
      produced by the Trichoderma harzianum isolate 1051 was purified to homogeneity by
      precipitation with ammonium sulfate followed by hydrophobic chromatography. The
      molecular mass of this protease as determined by SDS-polyacrylamide gel
      electrophoresis was about 18.8 kDa. Its N-terminal amino acid sequence shares no
      homology with any other protease. The purified enzyme substantially affected the
      cell wall of the phytopathogen C. perniciosa. Western-blotting analysis showed
      that the enzyme was present in the culture supernatant 24 h after the Trichoderma
      started to grow in casein-containing liquid medium. CONCLUSIONS: The capacity of
      the Trichoderma harzianum protease to hydrolyze the cell wall of C. perniciosa
      indicates that this enzyme may be actually involved in the antagonistic process
      between the two fungi. This fact strongly suggest that hydrolytic enzyme over
      producing transgenic fungi may show superior biocontrol capacity.

PMID- 11835697
TI  - LDL-cholesterol lowering effect of a generic product of simvastatin compared to
      simvastatin (Zocor) in Thai hypercholesterolemic subjects -- a randomized
      crossover study, the first report from Thailand.
AB  - BACKGROUND: It is commonly agreed that people with a high blood LDL-cholesterol
      will have a higher risk of coronary artery disease (CAD) than people with low
      blood LDL-cholesterol. Due to the increasingly high costs of medication in
      Thailand, the government has set up several measures to combat the problem. One
      of such strategies is to promote the utilization of locally manufactured drug
      products, especially those contained in the National Drug List. Simvastatin, an
      HMG-CoA reductase inhibitor, is listed as an essential drug for the treatment of
      hypercholesterolemia. Here, we reported the study on the LDL-cholesterol-lowering
      effect of a generic simvastatin product in comparison with the Zocor, in 43
      healthy thai volunteers. METHOD: The generic product tested was Eucor, locally
      manufactured by Greater Pharma Ltd., Part, Thailand, and the reference product
      was Zocor (Merck Sharp & Dohme, USA). The two products were administered as 10-mg
      single oral doses in a two-period crossover design. After drug administration,
      serial blood samples were collected every 4 weeks for 16 weeks. The major
      parameter monitored in this study was blood LDL-cholesterol. RESULT: After taking
      the drugs for the first 8 weeks, no statistically significant difference was
      detected in blood LDL-cholesterol between the first (Zocor-treated) and the
      second (Eucor-treated) groups. After crossover and taking drugs for further 8
      weeks, a similar result was obtained, i.e., no significant difference in blood
      LDL-cholesterol between the first (Eucor-treated) and the second (Zocor-treated)
      groups was observed. Upon completion of the 16-week study, there was also no
      statistically significant difference in the changes of all tested blood
      parameters between the two products (randomized block ANOVA, N = 37). Only minor
      side effects, mainly dizziness and nausea, were observed in both products.
      CONCLUSION: Our study demonstrated no significant differences in the therapeutic
      effect and safety between the generic and original simvastatin products.

PMID- 11835699
TI  - Thinking on trauma research.

PMID- 11835700
TI  - Mild to moderate hypothermia: the hope for improving outcome of severe head
      injured patients.

PMID- 11835698
TI  - Deconstructing patient centred communication and uncovering shared decision
      making: an observational study.
AB  - BACKGROUND: Patient centred communication (PCC) has been described as a method
      for doctor-patient communication. The principles of shared decision making (SDM)
      have been proposed more recently. AIMS: This study aimed to examine PCC and SDM
      empirically with respect to their mutual association, the variation in
      practitioners' working styles, and the associations with patient characteristics.
      METHODS: Sixty general practitioners recruited 596 adult patients who gave
      written consent to have their consultations videotaped. The tapes were assessed
      by two researchers, using a standardised instrument for global communication. For
      the purpose of this exploratory study, scales for PCC and SDM were based on
      subsamples of items in the MAAS. RESULTS: The scales for PCC and SDM were weakly
      associated (Pearson correlation: 0.25). Physicians varied more on SDM than on
      PCC. The intracluster correlation of the PCC and SDM scales were, respectively,
      0.34 and 0.19. However, hypotheses regarding associations with patient
      characteristics were not confirmed. Neither PCC nor SDM scores were related to
      patient gender, education, age, functional health status or existence of chronic
      conditions. CONCLUSION: The study provides evidence that PCC and SDM can be
      differentiated and comprise approaches to communication between clinicians and
      patients which may be more clearly distinguished by further focused research and
      training developments.

PMID- 11835701
TI  - Changes of evoked potentials and evaluation of mild hypothermia for treatment of
      severe brain injury.
AB  - OBJECTIVE: To observe the changes of evoked potentials after severe brain injury
      and the effect of mild hypothermia on acute severe brain injury. METHODS: A total
      of 44 patients with severe closed head injury (GCS 3-8, admitted within 10 hours
      from injury) admitted from May 1998 to March 1999 were selected for this study.
      All patients were admitted into the intensive care unit and divided into 2
      groups, Group A (GCS 3-5) and Group B (GCS 6-8). Patients were also randomly
      assigned to either normothermia or hypothermia subgroups. Patients in the
      hypothermia group were cooled to 32-34 degrees C. Median nerve short-latency
      somatosensory evoked potentials (SLSEP) and brain stem auditory evoked potentials
      (BAEP) were recorded before cooling and 4, 24, 48, 72, 96 and 120 hours,
      respectively after cooling and temperature resuming. SLSEP and BAEP were measured
      at the same time in the normothermia group (control group). The changes of evoked
      potentials (EP) were analyzed by statistical methods. RESULTS: In the Group B,
      N(20) amplitudes in SLSEP and I/V amplitudes in BAEP after mild hypothermia
      treatment in the hypothermia group differed significantly from those in the
      control group (P<0.05). However, in the Group A, no significant difference in all
      parameters was found. CONCLUSIONS: These results demonstrate that mild
      hypothermia treatment (32-34 degrees C) in the Group B has a significant
      neuroelectrophysiological effect on severe brain injury. Nevertheless, the effect
      of mild hypothermia in the Group A is not apparent and needs further studying.

PMID- 11835702
TI  - Inhibiting effect of moderate hypothermia on cell apoptosis after diffuse brain
      injury in rats.
AB  - OBJECTIVE: To explore the variant processes of cell apoptosis and the inhibiting
      effect of moderate hypothermia on cell apoptosis after diffuse brain injury.
      METHODS: Models of diffuse brain injury were induced by the trauma device
      reported by Marmarou. A total of 128 Wistar rats were divided into 4 groups: the
      uninjured group (Group A, n=8), the severely injured group (Group B, n=60), the
      mildly injured group (Group C, n=30) and the mild hypothermia group (Group D,
      n=30). In Group D, the severely injured rats were treated with moderate
      hypothermia to keep the rectal temperature at 32 degrees C (standard deviation
      for 0.1 degree C) for 6 hours. Then the morphology, the characteristics and the
      quantity of apoptotic cells in the cerebral cortex and in the hippocampus regions
      after different severities of craniocerebral injuries were observed and compared
      under an electronic microscope, with terminal deoxynucleotidyl nick end labeling
      (TUNEL) in DNA fragmentation and with agarose gel electrophoresis. RESULTS: TUNEL
      showed apoptotic cells increased according to the injury severity, and they
      peaked at 48 hours after injury and then declined. In Group C, apoptosis was
      located in the CA(2) and CA(3) areas of the hippocampus. And in Group B,
      apoptosis increased evidently, and located in the whole hippocampus and in the
      frontal and parietal cortex regions. The hypothermia-treated rats had some
      apoptotic cells, too. However, even at 24, 48 and 72 hours after injury there
      were significantly fewer apoptotic cells in the cortex and in the hippocampus in
      Group D than that in the non-treated groups. Electron microscopy showed that the
      apoptotic cells were round and shrunken in morphology and the nuclei were round
      and condensed at 24 and 48 hours after injury. And the apoptosis at 48 hours was
      more severe than that at 24 hours. The hypothermia-treated rats had no apoptotic
      cells. Gel electrophoresis showed that characteristic DNA "ladders" were observed
      in the cortex and in the hippocampus at 48 hours after severe injury. But there
      was no DNA "ladder" at other time points in the severely injured group, in the
      mildly injured group and in the hypothermia-treated group. CONCLUSIONS: It
      suggests that apoptosis occurs after diffuse brain injury and apoptotic cells
      increase with the injury severity. Moderate hypothermia has a specific inhibiting
      effect on cell apoptosis after diffuse brain injury in rats.

PMID- 11835703
TI  - Early monitoring of P(ti)O(2), P(ti)CO(2), pH and brain temperature in patients
      with brain injuries and the clinical significance.
AB  - OBJECTIVE: To explore the regulation of early brain tissue metabolic changing
      after brain injuries and the clinical significance. METHODS: There were 17
      patients with brain injuries. Early dire ct monitoring of P(ti)O(2), P(ti)CO(2),
      pH and brain temperature, dynamic observation of the relation between various
      parameters and clinics after brain injuries were performed. RESULTS: Early
      changes of P(ti)O(2), P(ti)CO(2) and pH were closely correlated with outcome. The
      death rate obviously increased when P(ti)O(2) was continuously lower than 9 mmHg
      within 24 hours after injuries. Secondary brain injury prolonged and aggravated
      brain tissue metabolic disturbance. When intracerebral pressure was over 30 mmHg
      P(ti)O(2) began to decrease. The brain temperature in brain death patients was
      evidently lower than axillary temperature. CONCLUSIONS: The direct monitoring of
      P(ti)O(2), P(ti)CO(2), pH and brain temperature is safe and accurate and can find
      early anoxia da mage to brain tissue and provide reliable basis for clinical
      therapy. It ha s an instructive significance in selecting and studying a new
      treatment method in brain injuries. And it can be taken as a criterion in
      clinical judging brain deaths.

PMID- 11835704
TI  - Retrospective study of mechanical ventilation in treating multiple trauma
      accompanied with craniocerebral injury.
AB  - OBJECTIVE: To explore the importance of mechanic al ventilation (MV) in treating
      multiple trauma mainly accompanied with cerebral injury and improve the treatment
      level. METHODS: All 116 patients who suffered from multiple trauma accompanied
      with mainly cerebral injury were analyzed. Rank correlation and Chi-square test
      were made between MV with GCS, ISS, and whether shock or not. RESULTS: The MV was
      correlated with GCS, ISS scores, and whether shock or not markedly. Furthermore,
      when GCS <or=8, the ratio of MV was about 70%. When ISS >or=35, the ratio of MV
      was about 85%. CONCLUSIONS: During the treatment of multiple trauma accompanied
      with cerebral injury, the principle of "early MV, early withdraw" and
      "individualism" should be insisted on. For patients accompanied with shock, the
      optimum PEEP is very important. Proper and active MV is of great importance and
      can improve the treatment level markedly.

PMID- 11835705
TI  - Clinical analysis on 149 old patients with craniocerebral injury.
AB  - OBJECTIVE: To study the clinical features of craniocerebral injury (CI) in the
      aged. METHODS: The data of 149 old patients with CI hospitalized in t he
      department from July 1991 to May 2000 were studied retrospectively in this study.
      The causes of injury, traumatic pathology, clinical manifestation and cause s of
      death were analyzed, too. RESULTS: Automobiles were the main victim-makers, and
      falls we re the second. And there was no significant difference between the first
      two kin ds of victim-makers. The patients suffered mainly from cerebral
      contusion, intracerebral hematomas and subdural hematomas, and relatively fewer
      from epidural hematomas. The scores of Glasgow Coma Scale (GCS) were related
      closely to the prognosis when hospitalized or before surgical treatment. The
      total mortality rate was 37.5% in this study. The main cause of death was brain
      injury. CONCLUSIONS: The old patients with CI have a high mortality rat e. And
      the causes of injury, traumatic pathology and clinical manifestation are peculiar
      in the aged.

PMID- 11835706
TI  - Dynamic changes of interleukin-1, interleukin-6 and tumor necrosis factor in
      intermingled skin graft in burned rats.
AB  - OBJECTIVE: To compare the dynamic changes of interleukin-1 (IL-1), interleukin-6
      (IL-6), and tumor necrosis factor (TNF) in intermingled skin graft with those in
      other types of skin grafts in rats. METHODS: A 10%-15% third-degree burn was
      created in 180 Sprague-Dawley (SD) rats. After removing the scar, skin grafts
      were performed on the open wounds immediately with autoskin (aus, n=54), alloskin
      (als, n=54) and intermingled skin (n=36). That is to say, in the intermingled
      skin graft, a big piece of alloskin (mals) was grafted first, and 3 days later,
      small pieces of autoskin (maus) wer e embedded in the alloskin. The rest 36 rats
      were taken as the controls. And the biological activities of IL-1, IL-6 and TNF
      in graft sheets in each group were detected after skin graft. RESULTS: The levels
      of IL-1, IL-6 and TNF in the aus group decreased steadily after their initial
      elevations, whereas in the als group they increased significantly and kept on the
      peak level in the later phases. In the in termingled group, there appeared a
      lowest IL-1 level in the mals and a highest one in the maus simultaneously at 7
      (4) days (The number out of parenthesis is t he days after transplanting with
      alloskin sheets, and the number in parenthesis is the days after embedding
      autoskin sheets in the intermingled skin graft. Similarly hereinafter.) after
      skin graft (P<0.01), and the high level in the maus abruptly decreased at 14 (11)
      days after skin graft. At exactly the same phase on day 7 (4), a prominent peaked
      IL-6 in the mals occurred. In the later phases, the levels of TNF remained
      relatively low both in the m als and in the maus. From day 7 (4) on, each
      cytokine fluctuation in the mals synchronized with that in the maus. The longer
      the post transplantation period lasted, the more the positive cytokine correlated
      between the mals and the maus. CONCLUSIONS: The low levels of IL-1 and TNF may be
      important f actors to lighten the intensity of local rejection in the
      intermingled skin graft. The temporarily peaked IL-6 is both an inducer which
      induces the production of local IL-1 receptor antagonists and soluble TNF
      receptors and a signal which indicates a local enhancement of Th(2) cells. The
      mild rejection process and th e synchronized cytokine level during the later
      phases suggest a possible chimerism between the mals and the maus.

PMID- 11835707
TI  - Animal study on lung injury caused by simulant segmented shock waves.
AB  - OBJECTIVE: To study the lung injury caused by segmented shock waves. METHODS: A
      total of 60 rabbits and 20 rats were used in this study. The process of
      transmission of shock waves was divided into three phases, i.e., the
      recompression phase (RP), the decompression phase (DP) and the underpressure
      phase (UP). And the recompression wave (RW), the decompression wave (DW) a nd the
      underpressure wave (UW) simulated the three phases, respectively, generated by
      the equipment designed by us. The RW test, DW test and UW test were respectively
      applied to the animals. And lung injuries caused by segmented shock waves were
      discussed. RESULTS: Under the experimental conditions, the RW did not cause
      obvious lung injury, but the DW could cause different severities of lung
      injuries. The greater the decompression ranged and the shorter the decompression
      duration was adopted, the more severe the lung injury was observed. The UW, to
      some extent, could cause obvious lung injury. CONCLUSIONS: It suggests that lung
      injury under shock waves probably occurs during the DP primarily. It probably
      does not cause direct obvious lung injury during the RP, but significantly
      influences the capability of causing lung injury during the DP.

PMID- 11835708
TI  - Remote therapeutic effect of early nerve transposition in treatment of
      obstetrical brachial plexus palsy.
AB  - OBJECTIVE: To report a method and remote therapeutic effect of early nerve
      transposition in treatment of obstetrical brachial plexus palsy. METHODS: From
      May 1995 to August 1996, 12 patients who had no recovery of biceps 3 months after
      birth were treated with nerve transposition. Eight had neuroma at the upper trunk
      and 4 had rupture or avulsion of the upper trunk. Mallet test was used to
      evaluate the results. RESULTS: The follow-up of 40-52 months showed that
      excellent and good recovery in functions was found in 75% of the patients and the
      excellent rate of phrenic nerve and accessory nerve transposition was 83.3% and 6
      6.7% respectively. A complete recovery in shoulder and elbow joint function was
      in 3 patients and Mallet IV was in 6 patients. CONCLUSIONS: Satisfactory outcome
      can be obtained by using early nerve transposition in treating obstetrical
      brachial plexus.

PMID- 11835709
TI  - Self-designed conical point contact plate and clinical application.
AB  - OBJECTIVE: To design a new kind of conical point contact plate (CPCP) in
      treatment of diaphyseal fracture to avoid further dam age to the blood supply of
      the cortex. METHODS: There were 4 pairs of conicles with a diameter of 1. 5-4 mm
      beneath the plate symmetrically. The nibs of the conicles were embedded about 1
      1.5 mm in the cortex by the axial force of screws. The conicle provided a gap
      about 2 mm between the plate and the bone so as not to compress the periosteum
      and cortex. And the periostem did not need to be stripped off during operation
      and there was no need of postoperative external fixation. RESULTS: Forty-two
      cases with diaphyseal fracture were stabilized by using CPCP. The patients could
      do joint exercise without loading after operation. Partial weight bearing could
      be performed in 4-6 weeks postoperatively. There was no obvious external callus
      in these cases. The average time of bone healing was 3 months in the tibia and
      forearm fracture and 4 months in the femur. Complications such as infection, non
      union or malunion etc. were not found. The implant was removed 6-10 months after
      operation. CONCLUSIONS: CPCP has the advantages of drastic reduction of the
      implant-to-bone interface virtually, elimination of the impairment of the
      periosteal blood supply, increase of the rate of healing and good stability which
      meets the need of early functional exercise.

PMID- 11835710
TI  - Traumatic extradural hematoma in the middle cranial fossa base: clinical analysis
      of 14 cases.
AB  - OBJECTIVE: To explore clinical characteristics, CT manifestation and operative
      indications of traumatic extradural hematoma in the middle cranial fossa base
      (EHMCFB). METHODS: A total of 14 cases with traumatic EHMCFB from January 1997 to
      May 2000 were retrospectively analyzed. RESULTS: Of 14 cases, 12 cases (85.7%)
      maintained form chan ge of cisterna ambiens for being pressed; 11 cases who
      received operations were all cured; 3 received conservative therapy, of whom 2
      became better and 1 died. CONCLUSIONS: In traumatic EHMCFB, the form change of
      cisterna ambiens occurs easily. Therefore, if there appears progressively
      aggravated form change of cisterna ambiens after the cisterna ambiens being
      pressed, an early a nd active operation is necessary and crucial.

PMID- 11835711
TI  - Treatment of recurrent traumatic carotid cavernous fistula via endovascular
      embolism technique.

PMID- 11835712
TI  - Misdiagnosis of eosinophilic ulcer of oral mucosa as squamous cell carcinoma in
      old patients.

PMID- 11835713
TI  - Hydraulic spinal cord and cauda equina nerve injuries.

PMID- 11835714
TI  - Review of papers published in the Chinese Journal of Traumatology (English
      Edition) in 2000.

PMID- 11835715
TI  - Clinical retrospective and comparative study on diaphragm injuries in 46 cases.
AB  - OBJECTIVE: To explore a way of guiding diagnosis and treatment of blunt and
      penetrating diaphragm injuries. METHODS: According to injury violence, 46 chest
      trauma patients with diaphragm rupture were divided into two groups: a blunt
      injury group and a penetrating injury group. The injury condition and trauma
      scores between the two groups were compared and analyzed. RESULTS: The incidence
      of blunt diaphragm injuries was lower than that of penetrating injuries (1.78% vs
      8.53%, P <0.05). In the blunt injury group most patients had multiple injuries.
      Penetrating injuries developed more quickly than blunt injuries, and resulted in
      hemorrhagic shock in the early period. Trauma scores showed that there was no
      significant difference in the Revised Trauma Score (RTS), the Injury Severity
      Score (ISS) and thoracic Abbreviated Injury Scale (AIS) between the two groups
      (P<0.05), but the blunt injury group had lower Glasgow Coma Scale (GCS) and
      abdominal AIS than the penetrating group (P<0.0 5). CONCLUSIONS: Blunt and
      penetrating diaphragm injuries have different clinical characteristics. So they
      should be dealt with differently to reduce the incidence of complication and
      improve prognosis.

PMID- 11835716
TI  - Relationship between changes of N-methyl-D-aspartate receptor activity and brain
      edema after brain injury in rats.
AB  - OBJECTIVE: To investigate the relationship between the changes of N-methyl-D
      aspartate (NMDA) receptor activity and brain edema after injury in rats. METHODS:
      The brain injury models were made by using a free-falling body. The treatment
      model was induced by means of injecting AP5 into lateral ventricle before brain
      injury; water contents in brain cortex were measured with dry-wet method; and
      NMDA receptor activity was detected with a radio ligand binding assay. RESULTS:
      The water contents began to increase at 30 minutes and reached the peak at 6
      hours after brain injury. The maximal binding (B(max)) of NMDA receptor increased
      significantly at 15 minutes and reached the peak at 30 minutes, then decreased
      gradually and had the lowest value 6 hours after brain injury. Followed the
      treatment with AP5, NMDA receptor activity in the injured brain showed a normal
      value; and the water contents were lower than that of AP5-free injury group 24
      hours after brain injury. CONCLUSIONS: It suggests that excessive activation of
      NMDA receptor may be one of the most important factors to induce the secondary
      cerebral impairments, and AP5 may protect the brain from edema after brain
      injury.

PMID- 11835717
TI  - The regulatory effect of ERK1/2 signal pathway on production of TNFalpha induced
      by LPS in mice Kupffer cells.
AB  - OBJECTIVE: To study the rule of ERK1/2 activity and regulative effect of ERK1/2
      pathway on the production of pro-inflammatory cytokine TNFalpha in mice Kupffer
      cells (mKC) induced by LPS, and to exploring novel methods to prevent and treat
      clinical patients of endotoxemia. METHODS: Immunoprecipitate kinase assay and
      Western blotting analysis were used to detect the phosphorylated ERK1/2 kinase
      activity in mKC stimulated by LPS, and ELISA was used to study the effect of
      ERK1/2 signaling cascade on LPS-induced TNFalpha production in mKC. RESULTS: In
      mKC, LPS treatment resulted in transient and rapid increase of kinase activity of
      ERK1/2 that phosphorylated their specific substrate ELK-1, with maximal value at
      30 minutes and a return near to baseline within 2 hours, and LPS-induced ERK1/2
      activity from LPS concentration of 10 pg/ml to the top activity at 100 ng/ml. No
      activity was observed in unstimulated mKC. Inhibition of the ERK1/2 pathway using
      the specific ERK1/2 signal pathway inhibitor PD98059 caused a marked and
      concentration-dependent reduction of TNFalpha production. CONCLUSIONS: The
      results show that LPS can markedly activate ERK1/2 pathway in mKC. PD98059 causes
      a significant and concentration-dependent reduction of TNFalpha production.
      ERK1/2 may be a novel target to treat clinical patient of endotoxemia.

PMID- 11835718
TI  - Retrograde interlocking intramedullary nailing under arthroscopy for
      supracondylar femoral fracture.
AB  - OBJECTIVE: To evaluate the therapeutic effects of retrograde interlocking
      intramedullary nailing under arthroscopy on supracondylar femoral fractures.
      METHODS: From June 1999 to December 2000, 17 patients with supracondylar femoral
      fracture were treated with arthroscopically assisted implantation of retrograde
      interlocking intramedullary nail and close reduction. RESULTS: More than 6-month
      follow-up study after operation in 11 patients revealed that the average healing
      time was 3 months. Average range of the knee motion for all the patients was more
      than 90 degrees. There was no implant breakage and infection. CONCLUSIONS: This
      new method, combining the advantage of arthroscope and retrograde interlocking
      intramedullary nail, can provide a stable and reliable fixation, and meanwhile is
      less invasive to the soft tissue and knee, less operative time and blood loss,
      minimal disruption of the blood supply in fracture site. It is conducive to the
      fracture healing and the functional recovery of the knee joint and worthwhile to
      be recommended.

PMID- 11835719
TI  - Effect of fetal spinal cord graft with different methods on axonal pathology
      after spinal cord contusion.
AB  - OBJECTIVE: To investigate the effect of fetal spinal cord (FSC) graft with
      different methods on axonal pathology and neurological function recovery after
      spinal cord injury (SCI). METHODS: Forty Wistar rats were divided into 4 groups.
      In Group A, the spinal cord was injured and hemisected. In Group B, fetal spinal
      cord (FSC) was transferred into the injured site. In Group C, after having done
      as Group B, the upper and lower spinal nerve roots were anastomosed. And in Group
      D, after having done as Group B, the pedicled omentum was transferred into the
      hemisection cavity. At 6 weeks after operation, light and electronic microscopes
      were used to examine the axonal pathology. The neurological function was assessed
      with inclined plane tests in the open field. The number of axons was quantitated
      by a computer image analysis system. RESULTS: A greater loss of axons was
      observed in Group A than that of other groups at 6 weeks. The sequence of the
      reduced rate of the axons was as following, Group A>Group B>Group C>Group D
      (P<0.05). The remaining axons were paralleled with the significant improvement in
      neurological function recovery of the rats. CONCLUSIONS: It indicates that FSC
      and pedicled omentum grafts after SCI can protect the axons and promote the
      neurological function recovery of the rats.

PMID- 11835720
TI  - Outcome of 2,284 cases with acute traumatic brain injury.
AB  - OBJECTIVE: To analyze the prognosis of 2284 cases with acute traumatic brain
      injury and discuss possible methods to improve the outcome of head injuries.
      METHODS: The relationship between trauma cause, trauma severity and management
      and patient's outcome was retrospectively analyzed. RESULTS: Good recovery was
      achieved in 60.20%, moderate disability was 13.22%, severe disability 15.24%,
      vegetative status 0.31% and mortality 11.03%. The mortality was 1.07% in cases
      with GCS 15-13, 2.47% in cases with GCS 12-9, 13.29% in cases with GCS 8-6, and
      57.4% in cases with GCS 5-3. CONCLUSIONS: To prevent hypoxia, remove intracranial
      hematoma as soon as possible, use standard large traumatic craniotomy and apply
      mild hypothermia may be useful means for improving the outcome of severely head
      injured patients.

PMID- 11835721
TI  - Outcome prediction in severe traumatic brain injury with transcranial Doppler
      ultrasonography.
AB  - OBJECTIVE: To investigate the value of transcranial Doppler (TCD) ultrasonography
      in evaluating the outcome of severe traumatic brain injury and to correlate the
      TCD values with intracranial pressure (ICP) and cerebral perfusion pressure (CPP)
      monitoring. METHODS: A prospective study was conducted to evaluate the
      contribution of TCD ultrasonography to neurological outcome in a series of 96
      severe traumatic brain injury patients. The quantitative variables of TCD
      ultrasonography included the mean blood flow velocity of the middle cerebral
      artery (MCA) and pulsatility index within the first 24 hours of admission. The
      ICP and CPP values were a lso recorded. Outcome in 6 months postinjury was
      evaluated using the Glasgow Outcome Scale (GOS 4-5 was considered as "good" and
      GOS 1-3 as "poor"). RESULTS: The mean blood flow velocity of the MCA was larger
      than 40 cm/s in 30 (51%) patients with good outcome whereas it was less than 40
      cm/s in 27 (73%) patients with poor outcome (P<0.025). The mean PI in cases of
      good outcome (34 patients, 57%) was lower than 1.5 whereas in poor outcome (30
      patients, 83%) was higher than 1.5 (P<0.001). The correlations of ICP and CPP to
      pulsatility index were statistically significant (P<0.01). CONCLUSIONS: TCD
      ultrasonography is valid in predicting the patient's outcome of 6 months and
      correlates significantly with ICP and CPP values when it is performed in the
      first 24 hours of severe traumatic brain injury.

PMID- 11835722
TI  - Early changes of arginine vasopressin and angiotensin II in patients with acute
      cerebral injury.
AB  - OBJECTIVE: To study the changes and clinical significance of arginine vasopressin
      (AVP) and angiotensin II (AT-II) in patients with acute moderate and severe
      cerebral injury. METHODS: The early plasma concentration was checked by
      radioimmunoassay in 47 cases of acute moderate and severe cerebral injury, 30
      cases of non-cerebral injury and 30 healthy volunteers. RESULTS: The early plasma
      concentrations of AVP (50.23 ng/L +/- 15.31 ng/L) and AT-II (248.18 ng/L +/-
      82.47 ng/L) in cerebral injury group were higher than those in non-cerebral
      injury group (AVP for 30.91 ng/L +/- 11.48 ng/L and AT-II for 120.67 ng/L +/-
      42.49 ng/L, P<0.01). The early plasma concentrations of AVP and AT-II in cerebral
      injury group were also obviously higher than those of the volunteers (AVP for
      5.16 ng/L +/- 4.23 ng/L and AT-II for 43.11 ng/L +/- 16.39 ng /L, P<0.001). At
      the same time, the early plasma level of AVP (58.90 ng/L +/- 18.12 ng/L) and AT
      II (292.13 ng/L +/- 101.17 ng/ L) was higher in severe cerebral injured patients
      than moderate cerebral injured ones (AVP for 36.68 ng/L +/- 12.16 ng/L and AT-II
      for 201.42 ng/L +/- 66.10 ng/L, P<0.01). The early level of AVP and AT-II was
      negatively related to the GCS scales in acute cerebral injury. The early plasma
      concentrations of AVP (45.98 ng/L +/- 13.48 ng/L) and AT-II (263. 28 ng/L +/-
      80.23 ng/L) were lower in epidural hematoma group than those of subdural hematoma
      and cerebral injury group (AVP for 64.12 ng/L +/- 15.56 ng /L and AT-II for
      319.82 ng/L +/- 108.11 ng/L, P<0. 01). CONCLUSIONS: AVP and AT-II may play an
      important role in pathophysiologic process in the secondary cerebral injury. The
      more severe the cerebral injury is, the higher the early level of AVP and AT-II
      will be. The early plasma level of AVP and AT-II may be one of the severity
      indexes of cerebral injury.

PMID- 11835723
TI  - Moderate hypothermia therapy for patients with severe head injury.
AB  - OBJECTIVE: To evaluate the effect and safety of early moderate hypothermia
      therapy (MHT) on patients with head injury by using parallel-control test.
      METHODS: Thirty patients with severe head injury within 6 hours after accidents
      were treated by MHT generally for 4-10 days. The other 30 patients with similar
      head injury treated routinely were enrolled for a parallel-control test. The
      mortality, morbidity and changes of some neuro-functional indexes as Glasgow Coma
      Scores, and Glasgow Outcome Scale, levels of endothelin and some other factors of
      neurobiochemistry in blood plasma were observed. Meanwhile, the dynamic
      monitoring by transcranial Doppler ultrasonography was conducted in these
      patients. RESULTS: The mortality in MHT group was significantly lower than that
      in control group. MHT not only reduced endothelin but also increased the brain
      biochemical factors, which were helpful to the protection of neurons in the early
      brain ischemia after head injury. CONCLUSIONS: Early MHT can help reduce
      mortality and morbidity in patients with acute head injury.

PMID- 11835724
TI  - Diagnosis and treatment of spinal fractures combined with paraplegia and
      diaphragm injury.
AB  - OBJECTIVE: To study the mechanism and treatment principle of spinal fractures
      combined with paraplegia and diaphragm injury. METHODS: A total of 16 patients
      (14 males and 2 females, aged from 18 to 50 years) with spinal fractures combined
      with paraplegia and diaphragm injury, receiving emergency treatment and admitted
      to our hospital in the past 20 years, were retrospectively analyzed in this
      study. RESULTS: The injuries were caused by direct or indirect violence. Six
      cases were of fractures of cervical spine combined with paraplegia and diaphragm
      injury, 2 of fractures of thoracic vertebra combined with paraplegia and
      diaphragm injury, and 8 of thoracolumbar fractures combined with paraplegia and
      diaphragm injury. Six cases received non-operative treatment, but died finally.
      Ten cases received spine surgical treatment, of which 4 died and 6 were improved.
      The total mortality rate was 62.5%. CONCLUSIONS: Spinal fractures combined with
      paraplegia and diaphragm injury are one of the most severe traumas in departments
      of orthopaedics. Paraplegia can be found easily, but diaphragm injury is often
      neglected and missed. When a patient suffers from both of them, he is in danger
      of death. What measures should be taken to rescue the patient's life depends on
      the severity of the wounds.

PMID- 11835725
TI  - Effects of nimodipine on changes of endothelin after head injury in rabbits.
AB  - OBJECTIVE: To investigate the effects of nimodipine on changes of endothelin
      after head injury. METHODS: Sixty-five adult rabbits were randomized into an
      injury group (IG, n=30), a nimodipine-treatment group (NTG, n=30) and a control
      group (CG, n=5). With their heads unfixed, the animals in IG and NTG were injured
      in the frontal-parietal zone with BIM-II bioimpact. Blood samples and brain
      tissue were collected before and after injury. The endothelin level was measured
      with RIA. RESULTS: The endothelin level in plasma and brain tissue was
      significantly increased 24 hours after injury. At the 8th or/and 24th hours
      postinjury, the endothelin level was significantly lower in NTG than that in IG.
      CONCLUSIONS: Nimodipine can prevent endothelin from elevation and act as a
      practical endothelin antagonist after head injury clinically.

PMID- 11835726
TI  - Pressure changes in spinal canal and evaluation of spinal cord injuries in spinal
      section subjected to impact.
AB  - OBJECTIVE: To observe pressure changes in the spinal canal of the vertebrarium
      subjected to impact. From the point of view of impact, pressure changes and
      spinal cord injuries, the relationship between the type of spinal fracture and
      the severity of spinal cord injuries were analyzed and some experimental data
      were provided for early evaluation of severity of spinal cord injuries. METHODS:
      An experimental model of spinal burst fracture was made with Type BIM-I bio
      impact machine and techniques of high velocity vertical loading in static pattern
      and stress shielding were adopted. Vertebral sections T10-L4 taken from fresh
      cadavers were impacted and pressure changes in the spinal canal were observed.
      The types and severity of spinal fracture were studied with gross and radiography
      examination. RESULTS: Great positive pressure wave (wave A) in the spinal canal
      of the 4 vertebral specimens with burst fracture was recorded. The peak value of
      pressure was correlated with the severity of posterior column injuries.
      Generally, the peak value of pressure was low in the samples with posterior
      column injuries, but high in the samples without injuries. The predominant
      features of fractures were burst fractures of vertebral body and severe
      destruction of the skeletal and fiber structure of the spinal canal. Positive and
      negative pressure waves (wave B) were recorded in 2 vertebral samples in which no
      significant abnormal changes were found by radiography examination, however, a
      little liquid effusion in the vertebral body was found by gross examination.
      CONCLUSIONS: The type of pressure wave in the spinal canal is related to the
      deformation or the destruction of the spinal canal structure. The peak value of
      the pressure is non-linearly related to the obstruction in the spinal canal, but
      related to posterior column injuries.

PMID- 11835727
TI  - Treatment of distal femoral nonunion and delayed union by using a retrograde
      intramedullary interlocking nail.
AB  - OBJECTIVE: To analyze the causes of distal femoral nonunion and delayed union and
      assess the outcome of the corresponding treatment, retrograde intramedullary
      interlocking nail (RIIN). METHODS: From June 1995 to December 1998, 15 patients
      (9 males and 6 females) with distal femoral nonunion and delayed union were
      treated with RIIN. The average age of the patients was 34.5 years (23-46 years).
      Bone grafting was performed in 10 patients, closed reaming was done in the other
      5 patients. Correction osteotomy was performed in 2 patients, and intra-articular
      release of knee adhesion in 11 patients. X-ray examination and knee society
      clinical rating system (KSS) were used to evaluate the results. RESULTS: All
      fractures were followed up for at least 9 months with average follow-up duration
      of 14.5 months (9-33 months). Solid union was documented in all patients at 6.4
      months on average. There were no infections or malunions in this series. Based on
      the final follow-up data, acceptable functional range of motion (ROM) of over 90
      degrees was achieved in most patients. The average ROM was 93.5 degrees with
      significant improvement of 28 degrees (42.7%, P<0.05) compared with the
      preoperative ROM. The average knee score was 96. Excellent ROM emerged in 13
      patients. The knee function score was 90.5 on average. CONCLUSIONS: The main
      causes of distal femoral nonunion and delayed union are improper indications and
      improper use of the implants. RIIN is an effective alternative for treatment of
      distal femoral nonunion and delayed union because it can provide a stable and
      reliable fixation which is beneficial for early functional exercise of knee. Bone
      grafting, closed reaming and intra-articular release of knee adhesion should be
      considered in order to enhance the bone healing and improve ROM and the knee
      function.

PMID- 11835728
TI  - Cranial penetration injury caused by a reinforcing steel bar.
AB  - One case of cranial penetration injury was reported caused by a reinforcing steel
      bar. The patient was well cured and discharged. After six years of follow-up, the
      patient had good functional recovery.

PMID- 11835729
TI  - Early treatment of wounds polluted by sea water.
AB  - During construction or training at sea, wounds are commonly seen and irresistibly
      polluted by sea water. An early and proper treatment of wounds polluted by sea
      water is very important for wound healing and function recovery of extremities.
      Some wounds even result in vegetation. In this study, we have reported the
      treatment results of 132 cases of wounds polluted by sea water admitted from 1985
      to 1999.

PMID- 11835730
TI  - Relationship between hyperventilation and intracranial pressure in patients with
      severe head injury.
AB  - With high fatality rate and disability rate, the pathophysiologic changes of
      severe head injury are complicated. But the method of lowering intracranial
      pressure (ICP) through artificial hyperventilation is called in question
      recently. To understand the related changes of the partial pressure of carbon
      dioxide in artery (PaCO(2)) and the ICP at the acute period of severe head
      injury, a total of 64 patients with severe head injury were monitored and
      analyzed on the 3rd day after injury.

PMID- 11835731
TI  - Anatomic basis of vascularized ulnar nerve graft by the pedicle of the superior
      collateral ulnar artery.
AB  - OBJECTIVE: To investigate the anatomic basis of vascularized ulnar nerve graft by
      the pedicle of the superior collateral ulnar artery (SCUA). METHODS: Twenty-two
      fresh cadaver upper extremities injected i ntra-arterially with latex were
      dissected to study the extrinsic blood supply of the ulnar nerve. Other 6 fresh
      upper extremities were used to analyze the blood supply range of SCUA inside the
      ulnar nerve by microangiographic and histological methods. RESULTS: The ulnar
      nerve was supplied by a branch of the lateral thoracic artery or directly by the
      axillary artery in the axillary section, by b ranches of SCUA in the upper arm,
      and by branches from the anastomosis of the collateral arteries and the posterior
      branch of the recurrent ulnar artery in the elbow. SCUA could supply the whole
      ulnar nerve from the axilla to the wrist. CONCLUSIONS: The ulnar nerve can be
      used as a vascularized nerve graft by the pedicle of SCUA in treatment of
      brachial plexus roots avulsion by C7 transfer from healthy side.

PMID- 11835732
TI  - Alpha 1-antitrypsin and alpha 1-acid glycoprotein reduce the sensitivity of human
      dermal fibroblast to endotoxin.
AB  - OBJECTIVE: To test the hypothesis that acute phase reactants, such as alpha 1
      antitrypsin and alpha 1-acid glycoprotein, could protect mammalian cells from
      further damage. METHODS: Human dermal fibroblasts (5 x 10(4)) were cultured with
      DMEM plus 10% FBS at 37 degrees C in a 5% CO(2) incubator. Different doses of LPS
      (lipo polysaccharide) and/or acute phase reactants were added. After 24 hours,
      the cultured supernatant was aspirated, the cells were washed, fixed and stained
      by methylene blue. The unbound stain was washed off. The stained cells were
      solubilize d in 0.1 ml of 1% Triton X-100. The absorbance of each well was
      measured us ing an ELISA spectrophotometer. The concentration of LPS which
      decreased the absorbance to 70% of the control (LPS-free) cultures was defined as
      LD(30). RESULTS: In order to achieve LD(30) in the presence of acute phase
      proteins, it was necessary to alter the LPS concentrations. The LD(3 0) of LPS
      treated with 0, 0.5, 2, 10 mg/ml antitrypsin and 0, 0.5, 2, 10 mg/ml glycoprotein
      was 5.4, 6.5, 7.6, 14.2 mg/ml and 5.2, 5.9, 6.9, 10.5 mg/ml, respectively.
      Statistically, with the treatment of more than 2 mg/ml antitrypsin or
      glycoprotein, LD(30) increased significantly. CONCLUSIONS: Our data show that
      fibroblasts are susceptible to the direct toxicity of LPS. Alpha 1-antitrypsin
      and alpha 1-acid glycoprotein can reduce the toxicity and/or increase the
      tolerance of mammalian cells to LP S.

PMID- 11835733
TI  - Clinical features of diffuse axonal injury.
AB  - OBJECTIVE: To analyze the mechanism of diffuse axonal injury (DAI) and study the
      relationship between DAI and brain concussion, brain contusion, and primary brain
      stem injury. METHODS: The clinical data and iconographic characteristics of 56
      patients with DAI were analyzed retrospectively. RESULTS: Traffic accidents were
      the main cause of DAI. Among t he 56 cases, 34 were injured for at least twice,
      and 71.43% of the patients were complicated with contusion. CONCLUSIONS: It is
      considered that DAI is a common pattern of primary brain injury, which is often
      underestimated. And DAI includes cerebral concussion and primary brain injury,
      and is often complicated by cerebral cortex contusion. Therefore, it is very
      simple and practical to divide primary brain injuries into local and diffuse
      injuries.

PMID- 11835734
TI  - Vascularized peripheral nerve trunk autografted in the spinal cord: a new
      experimental model in adult rats.
AB  - OBJECTIVE: To investigate the effect of vascularized peripheral nerve trunk
      autografted in spinal cord. METHODS: With modern microsurgical technique,
      vascularized peripheral median and ulnar nerve trunk autografted in the upper
      thoracic region of the spinal cord were established in 20 female adult rats. The
      origin and the termination of axons in the graft were studied by retrograde
      neuronal labeling with horseradish peroxidase (HRP). Cord, nerve grafts and some
      normal median an d ul nar nerves in the right upper limb were removed and
      sectioned for Bielschowsky's silver stain and haematoxylin and eosin (H&E) stain.
      Light and electron microscopic examination and electrophysiological examination
      were applied. RESULTS: The grafts were innervated by many new fibers. Studies
      with HRP indicated that new axons in graft were originated from intrinsic cent
      ral nervous system (CNS) neurons with their cell bodies from brain stem to s
      acral segments of spinal cord. Other axons arose from dorsal root ganglia at the
      level of graft and at least 19 distal segments to them. Together with electron
      microscopy, electrophysiological examination, silver and H&E stain, the results
      demonstrated that vascularized peripheral nerve trunk grafted in spinal cord
      attracted many neurons to grow into the nerve grafts. CONCLUSIONS: The findings
      implicate that CNS is able to regenerate much better in vascularized nerve
      autografted in spinal cord.

PMID- 11835735
TI  - Impairment of non-specific immunity in patients under persistent vegetative state
      resulting from trauma.
AB  - OBJECTIVE: To investigate the immune response in patients under persistent
      vegetative state (PVS) resulting from trauma. METHODS: Peripheral blood monocytes
      were obtained from 12 PVS patients (Group PVS)and individuals in normal control
      group by density gradient centrifugation; the enzyme linked immunosorbent assay
      kit was then used to measure monocyte HLA-DR antigen expression on the surface of
      peripheral blood monocytes before and after monocyte activation with either IFN
      gamma or LPS. RESULTS: Compared with normal control group, the peripheral blood
      monocyte HLA-DR antigen expression in the Group PVC fell significantly in PV S
      patients (P<0.001); the level of HLA-DR antigen express ion on the monocyte
      surface rose notably after stimulation with either IFN-gamma or LPS (P<0.01). As
      for PVS patients, it was still difficult to restore to normal (P<0.05).
      CONCLUSIONS: The level of HLA-DR antigen expression on the sur face of peripheral
      blood monocytes in PVS patients decreases obviously. Therefore, the function of
      non-specific immunity in PVS patients is suppressed.

PMID- 11835736
TI  - Association of HIF-1alpha expression and cell apoptosis after traumatic brain
      injury in the rat.
AB  - OBJECTIVE: To explore the expression of hypoxia inducible factor-1alpha (HIF
      1alpha) and the correlation between HIF-1alpha and apoptosis after traumatic
      brain injury. METHODS: Using experimental traumatic brain injury in the rats, the
      expression of HIF-1alpha was studied by immunohistochemistry in cerebral tissue,
      apoptotic cell death was evaluated with TUNEL (transferase-mediated X-dUTP nick
      end labeling), and double-labeled immunohistochemistry and TUNEL methods were
      used to investigate the relationship between HIF-1alpha and apoptosis. RESULTS:
      There was remarkable difference in the expression of H IF-1alpha between the
      experimental groups and the control groups (P<0.01), in the experimental groups,
      the expression of HIF-1alpha at 48 hours was highest; the evidence of apoptotic
      cell death after experimental traumatic brain injury was found by TUNEL; the
      apoptotic percentage increased or decreased according to the changes of the
      positive expression of HIF-1alpha (r=0.99). CONCLUSIONS: The results suggest that
      secondary brain ischemia plays a crucial role in apoptotic cell death after
      traumatic brain injury; HIF-1alpha can prompt apoptotic cell death after
      experimental traumatic brain injury.

PMID- 11835737
TI  - Imaging diagnosis of cervical spine and spinal cord injuries in children.
AB  - OBJECTIVE: To provide the experience in imaging diagnosis of cervical spine and
      spinal cord injuries in children. METHODS: Imaging data of cervical spine and
      spinal cord injuries in 62 children were retrospectively reviewed. The routine
      radiography including the lateral, anteroposterior and open-mouth odontoid views
      were performed in all the patients. Tomography was available for 25 patients, and
      flexion-extension lateral views for 28 patients, CT scanning for 21 patients, MRI
      for 26 patients. RESULTS: Of these patients, 46 patients were identified with in
      juries of upper cervical spine (9 with atlantal arch fracture, seven with axial
      fracture, 21 with odontoid fracture, 1 with atlantal arch fracture combining with
      odontoid fracture, and 1 with atlantal transverse ligament disruption); 7
      patients sustained injuries of lower cervical spine (3 fractures of vertebral
      body, 2 dislocations and 6 fracture-dislocations); 2 patients had multiple
      noncontiguous cervical injuries; and 3 had cervical spinal cord injury without
      radiographic abnormalities (SCIWORA). CONCLUSIONS: Imaging assessment is of great
      importance in the diagnosis of cervical spine and spinal cord injuries in
      children. Whenever cervical spine and spinal cord injuries are suspected for
      children patients, and the three-views should be routinely indicated. MRI should
      be routinely performed in all children with cervical SCIWORA.

PMID- 11835738
TI  - Comparative observation with MRI and pathology of brain edema at the early stage
      of severe burn.
AB  - OBJECTIVE: To investigate the correlation between MRI features and pathology in
      brain edema at the early stage of severe burn (5 0% TBSA III degree) in dogs.
      METHODS: Fifty-two dogs were randomized into control, simple b urn (SB), burn
      plus sodium lactate (BSL), and burn plus glucose solution groups (BGS). The
      manifestation of the brain of control group was compared with that of burn groups
      at 6, 12, 18 and 24 hours postburn with MRI and pathological examination (gross
      appearance, electron microscopy and light microscopy). RESULTS: The earliest
      findings of brain edema were seen at 12 h ours after burn in BGS group, in which
      brain swelling was the main feature of MR I. The decrease of SIR on T(1)WI was
      not observed until it was exceeded 10%. Sig nal of T(2)WI increased by 8.29% at
      24 hours after burn. It was difficult to distinguish the gray matter from the
      white matter at the boundary line, which became blurred later. Histological
      changes of brain edema were observed as early as 6 hours after burn, being
      accompanied by swelling of endothelial cells and peri-vescular astrocytes, and
      vacuolation took place in neurons at 12 hours after burn, with different degrees
      of necrosis of capillary endothelium, neurons, and axons. These changes became
      more marked with elapse of time. The BGS group showed the most obvious changes
      mentioned above at 24 hours after burn. CONCLUSIONS: The model of the brain edema
      after severe burn has the feature of both vasogenic edema and cytotoxic edema on
      the MRI and pathology. Positive MRI findings lagged behind that of the
      pathomorphological changes.

PMID- 11835739
TI  - Gene expression of inducible nitric oxide synthase in injured spinal cord tissue.
AB  - OBJECTIVE: To investigate gene expression of inducible nitric oxide synthase
      (iNOS) in injured spinal cord tissue of rats. METHODS: Thirty-six adult Sprague
      Dawley rats were divided randomly into six groups: a normal group and five injury
      groups, six animals in ea ch group. Animals in the injury groups were killed at
      2, 6, 12, 24, 48 hours after injury, respectively. A compression injury model of
      spinal cord was established according to Nystrom B et al, and gene expression of
      iNOS in spinal cord tissue was examined by means of reverse transcription
      polymerase chain reaction (RT-PCR). RESULTS: Gene expression of iNOS was not
      detectable in normal spinal cord tissue but was seen in the injury groups. The
      expression was gradually up -regulated, reaching the maximum at 24 hours. The
      expression at 48 hours began to decrease but was still significantly higher than
      that at 2 hours. CONCLUSIONS: iNOS is not involved in the normal physiological
      activities of spinal cord. Expression of iNOS is up-regulated in spinal cord
      tissue in response to injury and the up-regulation exists mainly in the late
      stage after injury. Over-expression of iNOS may contribute to the l ate injury of
      spinal cord.

PMID- 11835740
TI  - Trauma-related xanthogranulomatous interstitial nephritis: a clinicopathological
      analysis.
AB  - OBJECTIVE: To investigate the pathogenesis, exact nature, histologic feature of
      xanthogranulomatous interstitial nephritis (XGIN) as well as its significance in
      clinical medicine. METHODS: The medical histories concerned were collected with
      diagnostic images including CT scanning, ultrasonography, intravenous urography
      (IVU) and laboratory data being synthesized by comparison with what was discover
      ed during operations and pathologic examinations. RESULTS: All patients were ever
      struck on their loins or backs by blunt violence over 4-12 years. The diseases
      were clinically diagnosed as "renal cancer" before, during and after operations,
      and treated with ra dic al nephrectomy. Located at cortical parts, the tumor
      focus had penetrated the renal capsules and invaded other organs. However,
      immunohistochemistry demonstrated that the lesions were xanthogranulomas, not
      tumors, in which there were stacks of foam cells and lymphocytes with vast
      extends of fibrotic tissues obliterating the cortical interstitial structures.
      Urinary tracts yielded no bacterium, obstruction or calculus. CONCLUSIONS: XGIN
      is likely to be one kind of immunologic mediated granuloma following blunt renal
      trauma. It is imperative to clarify pathogenesis and character of this lesion so
      as to find out any approach to diagnosis and cure of such an unusual nephropathy.

PMID- 11835741
TI  - Glasgow Coma Scale, brain electric activity mapping and Glasgow Outcome Scale
      after hyperbaric oxygen treatment of severe brain injury.
AB  - OBJECTIVE: To study the effect of hyperbaric oxy gen (HBO) treatment of severe
      brain injury. METHODS: Fifty-five patients were divided into a treatment group
      (n=35 receiving HBO therapy) and a control group (n=20 receiving dehydrating,
      cortical steroid and antibiotic therapy) to observe the alteration of clinic GCS
      (Glasgow Coma Scale), brain electric activity mapping (BEAM), prognosis and GOS
      (Glasgow Outcome Scale) before a nd after hyperbaric oxygen treatment. RESULTS:
      In the treatment group GCS, BEAM and GOS were improved obviously after 3 courses
      of treatment, GCS increased from 5.1 to 14.6 (P<0.01-0.001),the BEAM abnormal
      rate reduced from 94.3% to 38% (P<0.01-0.001), the GOS good-mild disability rate
      was 83.7%, and the middle-severe disability rate was 26.3% compared with the
      control group. There was a statistic significant difference between the two
      groups (P<0.01-0.001). CONCLUSIONS: Hyperbaric oxygen treatment could improve
      obviously GCS, BEAM and GOS of severe brain injury patients, and effectively
      reduce the mortality and morbidity. It is an effective method to treat severe
      brain injury.

PMID- 11835743
TI  - Experiences and lessons about soft-tissue flaps covering of severe open tibial
      fracture.
AB  - OBJECTIVE: To sum up experiences and lessons ab out management of soft-tissue
      reconstruction in open tibial fracture over a 6-year period. METHODS: Twenty-two
      flap reconstructions were performed to tre at soft-tissue defect of 22 patients
      with open tibial fracture Type IIIB (Gustilo) from 1993 to 1998. The cases were
      analyzed and discussed retrospectively aft er follow up of 12-61 months. RESULTS:
      The size of the flap ranged from 6.6 cm(2) to 28.18 cm(2) and the rate of flap
      failure was 13.6%. Besides, 3 partial necrosis and 2 postoperative infections
      occurred in this series. CONCLUSIONS: For soft tissue defect of delayed open
      tibial fracture Type IIIB, flap reconstruction is still an optimal option. The
      experiences we obtained are 1) to design a triangular skin extension or a small Z
      plasty over the pedicle to reduce the flap tension; 2) to select a unilateral
      external fixation to provide convenience for any secondary manipulation; and 3)
      to use serial debridement to diminish flap failure.

PMID- 11835742
TI  - Allogeneic bone nail for articular fractures.
AB  - OBJECTIVE: To investigate the effect of allogeneic bone nail on articular
      fractures. METHODS: Ninety-one patients with cancellous bone fracture involved in
      various joints were fixed with the bone nail or the bone screw. No
      immunosuppressive agent was used in this series. The average period of follow-up
      wa s 18 months. RESULTS: All patients except one healed without displacement an d
      the healing time was within 1-3 months. Joint function was partially limited in 6
      patients and others were functioning well. CONCLUSIONS: Allogeneic bone nail
      possesses a good biological compatibility and intensity, thus provides a rigid
      fixation. Being completely absorbed and ossificated, thus obviating the need for
      secondary operation, is a suitable internal fixation material for the treatment
      of articular fractures.

PMID- 11835744
TI  - Decalcificated human dentin matrix in autogenous repair of skull defects.

PMID- 11835745
TI  - Pedicale screw system plus ACPC perfusion to treat fractures of thoracolumbar
      vertebrae.

PMID- 11835746
TI  - Surgical treatment for acute traumatic multiple intracranial hematomas.

PMID- 11835747
TI  - Gene expression of two kinds of constitutive nitric oxide synthase in injured
      spinal cord tissue.
AB  - OBJECTIVE: To investigate the gene expression of two kinds of constitutive nitric
      oxide synthase (cNOS): neuronal NOS (nNOS) and endothelial NOS (eNOS) in injured
      spinal cord tissue. METHODS: Thirty-six adult Sprague-Dawley rats were divided
      randomly into six groups: the normal group and the injury groups (2, 6, 12, 24,
      48 h after injury, respectively). A compression injury model of the spinal cord
      wa s ma de and gene expression of nNOS and eNOS were examined by reverse
      transcription polymerase chain reaction (RT-PCR). RESULTS: The gene expression of
      nNOS and eNOS was detected in the normal group and they were up-regulated quickly
      after injury, reaching the maximum at 6 h. There was no difference between gene
      expression of nNOS and eNO S in the normal group, but in each injury group the
      gene expression of eNOS was much higher than that of nNOS. CONCLUSIONS:
      Expression of constitutive NOS (cNOS) in spinal co rd tissue was up-regulated
      after injury mainly in the early stage. cNOS as a wh ole offers protection in
      spinal cord injury, but different cNOS may play different roles.

PMID- 11835748
TI  - Effect of nonoperative treatment on the outcome of patients with posttraumatic
      hydrocephalus.
AB  - OBJECTIVE: To compare the outcome of non-operative treatment with the outcome of
      surgical intraventricular drainage for patients with posttraumatic hydrocephalus
      including complications, mortality and favorable outcome. METHODS: Thirty-nine
      patients were assigned to a nonoperative treatment group and 38 patents to a
      surgical intraventricular drainage group. Each patient's outcome was evaluated 3
      years after treatment by using Glasgow Outcome Scale. RESULTS: In the
      nonoperative treatment group the rate of favor able outcome (good recovery or
      mild disability) was 89.74% (35 of 39 patients) and the mortality was 2.56% (1 of
      39 patients). In the surgical intraventricular drainage group the rate of
      favorable outcome was 71.05% (27 of 38 patients) and the mortality was 13.16% (5
      of 38 patients; P<0.05). Mortality was not significantly different between the
      two groups. CONCLUSIONS: Nonoperative treatment may be better than surgical
      intraventricular drainage for patients with posttraumatic hydrocephalus.

PMID- 11835749
TI  - Effect of anti-sense oligodeoxynucleotides homeobox B2 on the proliferation and
      expression of primary human umbilical vein endothelial cells.
AB  - OBJECTIVE: To explore the effect of homeobox B2 (HOXB2) anti sense
      oligodeoxynucleotides (asodn) on the proliferation and expression of primary
      human umbilical vein endothelial cells (HUVECs). METHODS: Various concentrations
      of HOXB2 asodn modified by thiophosphate transfected the induction of liposome
      into HUVECs. MTT a nd RT-PCR methods were employed to determine the effect of
      different conc ent rations of asodn on the endothelial proliferation and the
      expression level of HOXB2 mRNA. RESULTS: After the transfection of HOXB2 asodn,
      the endothelial proliferation was inhibited in a dose-dependent fashion.
      Simultaneously, the expression of HOXB2 mRNA decreased significantly.
      CONCLUSIONS: HOXB2 plays an important role in the proliferation of endothelia.

PMID- 11835750
TI  - Study of L-arginine-nitric oxide pathway in ischemia-reperfusion injured limbs in
      rats.
AB  - OBJECTIVE: To observe the change of nitric oxide (NO) levels in the blood and the
      morphological change of the muscles in the limbs of rats during the (IR) injury
      and after being intervened by L-arginine (L-Arg) and L-nitroarginine (L-NNA).
      METHODS: Sixty-six male Sprague-Dawley (SD) rats were used an d grouped into the
      normal controls, the sham injury controls, the IR injury group and the
      intervention groups (L-Arg group and L-NNA group). After 6 hours of ischemia,
      followed by reperfusion for 3, 12 or 24 hours, the samples in the IR injury group
      were obtained. The rats in the intervention groups were given L-Ar g (100 mmol/L)
      and L-NNA (10 mmol/L), respectively, through the abdominal cavity. Then the
      anterior tibial muscle in the right limb was obtained for histological
      examination, the anterior tibial muscle in the left limb for ultrastructure
      observation and the blood for assay of NO in all the rats. NO was assayed by
      indirect measurement of NO(2)(-)/NO(3)(-) with Griess method. RESULTS: There was
      no significant difference of NO between the normal controls and the sham injury
      controls (P>0.05). But NO significantly decreased in the IR injury group
      (P<0.01), and further decreased with reperfusion (P<0.01) and reached the lowest
      point at 12 hours after reperfusion. The level of NO in the L-Arg group was
      significantly higher than that in the IR injury group ( P<0.01), but was not
      significantly different from that in the controls (P>0.05). In the L-NNA group,
      NO decreased to the undetectable level (P<0.01). Histological examination and
      ultrastructure observation showed the muscles were normal in the control groups.
      After 6 hours of ischemia, the skeletal muscles displayed injuries, and they were
      most severely injure d after 12 hours of reperfusion. In the L-Arg group, the
      skeletal muscles were less injured, while in the L-NNA group, the injury was
      similar to that in the I R injury group. CONCLUSIONS: When the limbs of the rats
      sustain IR, NO in the blood decreases. Meanwhile, the muscles in the limbs are
      injured. When L-Arg is given, NO in the blood is restored and the muscles are
      protected. When L-NNA completely inhibits NO, no protection of the muscles is
      shown.

PMID- 11835751
TI  - Diagnosis and treatment of renal trauma in 298 patients.
AB  - OBJECTIVE: To investigate the diagnosis and treatment of renal trauma. METHODS:
      Retrospective analysis of 298 patients with renal trauma was carried out. Among
      them, 272 (91.3%) had blunt renal injuries and 26 (8.7%) had penetrating
      injuries; 123 (41.3%) had multiple complicated intraabdominal injuries and 56
      (18.8%) had concomitant shock. Normal-dose-IVU examination was used in 39
      patients and double-dose-IVU in 44 patients, ultrasonography in 109 patients, and
      CT in 45 patients. Conservative and supportive therapy was done in 193 patients
      (64.8%) and operation in 105 patients (35.2%). RESULTS: The positive rate was
      48.7% by the normal-dose-I VU examination and 90.9% by double-dose-IVU, 78.8% by
      ultrasonography, and 95.6% by CT. One hundred and eighty-three patients were
      cured by conservative therapy and 101 by operation. Fourteen patients died.
      CONCLUSIONS: B-ultrasound can be conveniently used for primary assessment of
      renal injuries, while CT shows rapid, accurate and proper condition of a renal
      trauma patient. The treatment depends on the severity of the injury. The
      conservative therapy is employed in most cases which present slight or moderate
      injury and no evident massive bleeding. Severe injury requires surgical
      exploration. The operative approach is by using a transabdominal incision, which
      makes it relatively easy to explore intraabdominal organs and control the injured
      kidney. It is also very important to control shock and prevent other severe
      complications in the early stage of the treatment.

PMID- 11835752
TI  - Spatial and temporal profile of apoptosis following lateral fluid percussion
      brain injury.
AB  - OBJECTIVE: To investigate the spatial and temporal profile of neural cell
      apoptosis following traumatic brain injury (TBI). METHODS: In addition to
      morphological evidence of apoptosis, TUNEL histochemistry assay was used to
      identify DNA fragmentation in situ at both light and electron microscopic levels,
      whereas characteristic internucleosomal DNA fragmentation of apoptosis was
      demonstrated by DNA gel electrophoresis. RESULTS: Using TUNEL method, we detected
      massive cells with extensive DNA fragmentation in different regions of the brains
      of rats subjected to experimental traumatic brain injury. Compared with the sham
      controls, in the injured cortex, the apoptotic cells were detectable for up to 24
      h and reached a peak at 1 week after injury. The number of apoptotic cells in the
      white matter h ad a significant increase as early as 12 h after injury and peaked
      at 1 wee k. The number of apoptotic cells increased in the hippocampus at 72 h,
      whereas i n the thalamus, the peak of apoptotic cells was at 2 weeks after
      injury. The number of apoptotic cells in most regions returned to sham values 2
      months after in jury. Gel electrophoresis of DNA extracted from affected areas of
      the injured br ain revealed only internucleosomal fragmentation at 185-bp
      intervals, a feature originally described in apoptotic cell death. And no DNA
      ladder was detectable in the cortex and hippocampus contralateral to the injured
      hemisphere. CONCLUSIONS: These data suggest that in addition to the well
      described necrotic cell death, a temporal course of apoptotic cell death is
      initiated after brain trauma in selected brain regions.

PMID- 11835753
TI  - Prosthetic replacement in treatment of subcapital femoral neck fractures in the
      elderly.
AB  - OBJECTIVE: To compare the results of femoral head replacement (FHR) and total hip
      replacement (THR) in treatment of subcapital femoral neck fractures (SFNF).
      METHODS: Between May 1987 and July 1998, 56 elderly patients (6 5-90 years;
      average 73.5 years) with SFNF were treated with prosthetic replacement. Six cases
      were treated with unipolar FHR, 18 cases with Bateman bipolar FHR, and 32 cases
      with Bateman bipolar THR. All domestic prostheses were installed with cement.
      RESULTS: There was no significant difference between the 2 groups in operating
      time and blood transfusion. Forty-nine patients were followed-up for an average
      of 5 years and 10 months. No wound infection or death was related to surgery.
      Complications in Group FHR were significantly higher than that i n Group THR.
      CONCLUSIONS: Since FHR is difficult to fit the bony acetabulum, it is only
      indicated for senile cases with poor conditions. However, the bi polar THR
      installed with cement is indicated for most elderly patients. Since th e femoral
      head and acetabulum can fit each other completely, it is more stable for taking
      weight-bearing earlier with less complications.

PMID- 11835754
TI  - Experimental study on the apoptosis of the astrocytes and the oligodendrocytes
      induced by Ca(2+) reperfusion.
AB  - OBJECTIVE: To investigate the apoptosis rules of the astrocytes and
      oligodendrocytes induced by Ca(2+) reperfusion. METHODS: The apoptosis of
      purified cultured astrocytes and oligodendrocytes induced by Ca(2+) reperfusion
      and the relationship between the development of the cell apoptosis and post
      reperfusion time was observed. RESULTS: Both the astrocytes and oligodendrocytes
      were obviously in a time-dependent fashion, and the apoptosis ratios of the
      oligodendrocytes (39.73%+/-4.16%) were higher than the astrocytes (19.64%+/
      4.67%) 24 hours after Ca(2+) reperfusion. The TUNEL positive cells were 13.6+/
      1.82 and 21.4+/-1.95 at every visual field of astrocytes and oligodendrocytes
      respectively 24 hours after Ca(2+) reperfusion. CONCLUSIONS: The astrocytes and
      oligodendrocytes are similar wi th the development rules on apoptosis and have
      different susceptiveness to the situation.

PMID- 11835755
TI  - Study on cognition disorder and morphologic change of neurons in hippocampus area
      following traumatic brain injury in rats.
AB  - OBJECTIVE: To explore the correlation between cognition disorder and morphologic
      change of hippocampal neurons after traumatic brain injury (TBI). METHODS: Wistar
      rat models with severe TBI were made by Marmarou's method. The histopathological
      change of the neurons in the hippocampus area were studied with hematoxylin-eosin
      (HE) staining and terminal deoxynucleotidyl transferase-mediated X-dUPT nick end
      labeling (TUNEL), respectively. The cognitive function was evaluated with the
      Morris water maze test. RESULTS: The comprehensive neuronal degeneration and
      necrosis could be observed in CA2-3 regions of hippocampus at 3 days after
      injury. Apoptotic positive neurons in CA2-4 regions of hippocampus and dentate
      gyrus increased in the injured group at 24 hours following TBI. They peaked at 7
      days and then declined. Significant impairment of spatial learning and memory was
      observed after injury in the rats. CONCLUSIONS: The rats have obvious disorders
      in spatial learning and memory after severe TBI. Meanwhile, delayed neuronal
      necrosis and apoptosis can be observed in the neurons in the hippocampus area. It
      suggests that delay ed hippocampal cell death may contribute to the functional
      deficit.

PMID- 11835756
TI  - Changes of intracellular calcium and the correlation with functional damage of
      the spinal cord after spinal cord injury.
AB  - OBJECTIVE: To observe dynamic changes of intracellular calcium ([Ca(2+)]i) after
      spinal cord injury, and to study the relationship between the changes of
      [Ca(2+)]i and the functional damage of the spinal cord. METHODS: The rats were
      subjected to a spinal cord contusion by using a modified Allen's method. The
      [Ca(2+)]i in the injured segment of the spinal cord was measured by the technique
      of La(3+) blockage and atomic absorption spectroscopy at 1, 4, 8, 24, 72, and 168
      hours after injury. The motor function on the inclined plane was measured at the
      same time. RESULTS: The spinal cord [Ca(2+)]i increased significantly (P<0.05 or
      P<0.01) aft er spinal cord injury. There was a significant correlation (P<0.05)
      between the changes of [Ca(2+)]i and the motor function. CONCLUSIONS: [Ca(2+)]i
      overload may play an important role in the pathogenesis of spinal cord injury.

PMID- 11835757
TI  - Effect of mild hypothermia on partial pressure of oxygen in brain tissue and
      brain temperature in patients with severe head injury.
AB  - OBJECTIVE: To study the changes of partial pressure of oxygen in brain tissue
      (P(bt)O(2)) and brain temperature (BT) in patient s in acute phase of severe head
      injury, and to study the effect of mild hypothermia on P(bt)O(2) and BT. METHODS:
      The P(bt)O(2) and the BT of 18 patients with severe head injury were monitored,
      and the patients were treated with mild hypothermia within 20 hours after injury.
      The rectal temperature (RT) of the patients was kept on 31.5-34.9 degrees C for 1
      7 days (57.7 hours+/-28.4 hours averagely), simultaneously, the indexes of
      P(bt)O(2) and BT were monitored for 1-5 days (with an average of 54.8 hours+/
      27.0 hours). According to Glasgow Outcome Scale (GOS), the prognosis of the
      patients was evaluated at 6 months after injury. RESULTS: Within 24 hours after
      severe head injury, the P(bt)O(2) was significantly lower (9.6 mm Hg+/-6.8 mm Hg,
      1 mm Hg=0.133 kPa) than the normal value (16-40 mm Hg). After treatment of mild
      hypothermia, the mean P(bt)O(2) increased to 28.7 mm Hg+/-8.8 mm Hg during the
      first 24 hours, and the P(bt)O(2) was still maintained within the range of normal
      value at 3 days after injury. The BT was higher than the RT in the patients in
      acute phase of severe head injury, and the difference between the BT and the RT
      significantly increased after treatment of mild hypothermia. Hyperventilation
      (the partial pressure of carbon dioxide in artery (P(a)CO(2)) approximately 25 mm
      Hg) decreased the high intracranial pressure (ICP) and significantly decreased
      the P(bt)O(2). CONCLUSIONS: This study demonstrates that P(pt)O(2) and BT
      monitoring is a safe, reliable and sensitive diagnostic method to follow cerebral
      oxygenation. It might become an important tool in our treatment regime for
      patients in the acute phase of severe head injury requiring hypothermia and
      hyperventilation.

PMID- 11835758
TI  - Mechanism of macrophage injury following traumatic hemorrhagic shock: through PTX
      sensitive G-protein-mediated signal transduction pathway.
AB  - OBJECTIVE: To study the mechanism of macrophage injury after trauma-hemorrhagic
      shock. METHODS: Wistar male rats underwent trauma (closed bone fracture) and
      hemorrhage (mean arterial blood pressure of 35 mm Hg+/-5 mm Hg for 60 minutes,
      following fluid resuscitation). Rats without trauma, hemorrhage or fluid
      resuscitation served as controls. Peritoneal macrophages were harvested at 6
      hours and 1, 2, 3, 7 days after traumatic hemorrhagic shock to determine the
      effects of pertussis toxin (PTX, as a specific inhibitor to Gi(alpha) and cholera
      toxin (CTX, as a stimulant to Gs(alpha) on macrophage-Ia expression and TNF-alpha
      production and levels of Gi(alpha) and Gs(alpha). RESULTS: The macrophages from
      the injured rats revealed a significant decrease of Ia positive number and TNF
      alpha release in response to LPS. Wi th pretreatment with PTX 10-100 ng/ml Ia
      positive cells and LPS-induced TNFalpha production in both control and impaired
      macrophages populations were dos e dependently increased. Both macrophages
      populations were not responding to CTX treatment (10-100 ng/ml). Western blot
      analyses showed that the levels of Gi(alpha) protein expression increased as much
      as 116.5%-148.8% of the control level fro m 6 hours through 7 days after
      traumatic hemorrhage. The levels of Gs protein expression were reduced at 6 hours
      and decreased to the lowest degree; 36% o f the control at day 1, began to return
      at day 2 and returned to the normal level at day 7, following traumatic
      hemorrhagic shock. CONCLUSIONS: PTX-sensitive G-protein may participate in th e
      modulation of macrophage-Ia expression and TNF-alpha release following traumatic
      hemorrhagic shock. Analyses of the alteration of Gi(alpha) and Gs protein express
      ions further supports the concept that G-protein is involved in trauma-induced
      macrophage signal transduction pathways.

PMID- 11835759
TI  - Study on characteristics of fractures from road traffic accidents in 306 cases.
AB  - OBJECTIVE: To investigate the characteristics of bone fractures from road traffic
      accidents and analyze their injury mechanisms so as to provide reference for the
      research and medical care of traffic trauma. METHODS: Three hundred and six
      patients with fractures from road traffic accidents were included into this
      study. A total of 507 fractures were identified and the injury mechanism,
      location distribution and frequency were analyzed. RESULTS: The most common
      location of fractures was the lower extremities, followed by the upper
      extremities, skull and maxillofacial region, and the rarest was the spine. A
      total of 56% of the patients suffered from multiple fractures. The fractures of
      the patella, femur and pelvis and the fractures of the olecranon, humerus and
      shoulder often happened simultaneously. CONCLUSIONS: The injury mechanisms can be
      classified into four types: impact, incoordinate movement, stretch injury and
      crush and extrusion. The fractures from traffic accidents have the following
      characteristics: centrifugal distribution of the injuries, multiple fractures,
      force transmission and ipsilateral occurrence.

PMID- 11835760
TI  - Toll-like receptor 4, a novel signal transducer for lipopolysaccharide.

PMID- 11835761
TI  - Anterior internal fixation to treat vertical unstable pelvic fracture.

PMID- 11835762
TI  - First aid treatment of critically acute epidural hematoma complicated by cerebra
      l hernia using cranial trepanation and drainage decompression: a report of 16
      cases.

PMID- 11835763
TI  - [Clinical diagnosis of fungal keratitis by confocal microscopy].
AB  - OBJECTIVE: To illustrate the value of confocal microscope in the diagnosis of
      fungal keratitis. METHODS: In vivo confocal microscopy was performed on 43
      patients of suspected fungal keratitis. The results were compared to that of
      smears and biopsies. RESULTS: Fungal filaments were imaged in 31 of 43 patients'
      corneas. Fungal keratitis was diagnosed in 32 patients based on clinical signs
      and all the methods of examinations. The positive rate of confocal microscopy is
      96.9%. CONCLUSION: Confocal microscopy can be a rapid, effective and noninvasive
      imaging technique, and it is helpful in the diagnosis, treatment and study of
      fungal keratitis.

PMID- 11835764
TI  - [Clinical and immunological studies on transplantation of total cornea with
      circular lamellar sclera].
AB  - OBJECTIVE: To observe the clinical results of total cornea with circular lamellar
      sclera transplantation (CST) and study its immunological mechanisms by animal
      experiments. METHODS: 109 patients with corneal transplantation were
      retrospectively analyzed, and according to the methods of operation they were
      divided into groups to compare their rate of rejection and the time of occurrence
      of corneal neovascularization. The methods of grouping and operation in animal
      experiments were similar to that in the clinical practice. RESULTS: The time of
      occurrence of neovascularization and rejection of CST were later than that in the
      total corneal transplantation (TCT), and the postoperative rate of rejection at 3
      to 6 months was obviously increased in comparison with that in the partial
      penetrating keratoplasty (PKP). CONCLUSION: CST is an important method for
      rebuilding ocular anterior segment, and the donor limbus is active in the
      immunological of rejection.

PMID- 11835765
TI  - [Expression of nuclear transcription factor NF-kappaB in human corneal
      fibroblasts].
AB  - OBJECTIVE: To explore the constitutive expression and activation of nuclear
      transcription factor NF-kappaB in corneal fibroblasts. METHODS: 2 or 3 passage
      corneal fibroblasts cultured in vitro were divided into two groups after
      synchronization. One group was cultured in DEME free of serum; the other in DEME
      with 10 microg/ml lipopolysaccharides for 6 hours. NF-kappaB was studied by flow
      cytometry (FCM) technique using immunofluorescent staining, and by gel shift
      assay (EMSA) using gamma-(32)P labeled NF-kappaB oligonucleotide probe. RESULTS:
      According to FCM results, there were constitutively 9.4% NF-kappaB positive
      corneal fibroblasts, and 2.2 folds more (30.0%) after stimulated with
      lipopolysaccharides. Using EMSA method, we demonstrated the existence of NF
      kappaB with DNA binding activity in the stimulated nuclei. CONCLUSION: There is
      nuclear transcription factor NF-kappaB in human corneal fibroblasts. When
      activated, cells express more transcription factor which can enter nuclei, bind
      itself to the related DNAs and play a regulatory role of gene transcription.

PMID- 11835766
TI  - [Cytokine assays for pterygium].
AB  - OBJECTIVE: To study the roles of tumor necrosis factor (TNF-alpha) and platelet
      derived growth factor (PDGF) in pathogenesis of pterygium. METHODS:
      Radioimmunoassay and bioactivity assay were used to measure the levels of TNF
      alpha and PDGF in tissue culture supernatant of pterygium specimens obtained from
      30 patients. RESULTS: The levels of TNF-alpha and PDGF in tissue culture
      supernatant of pterygium were significantly higher than that of normal
      conjunctival specimens (t = 2.827, P < 0.01; t = 3.011, P < 0.01), and there was
      a significant difference between progressive and quiescent cases (t = 2.374, P <
      0.05; t = 2.712, P < 0.05). CONCLUSIONS: The abnormal secretion of TNF-alpha and
      PDGF may be related to the pathogenesis of pterygium.

PMID- 11835767
TI  - [A study on proliferation and differentiation of limbal stem cells].
AB  - OBJECTIVE: To study the proliferation and differentiation of limbal stem cells
      (LCs) in vitro and examine the effects of epithelial growth factor (EGF) on cell
      proliferation. METHODS: The cells were cultured in DMEM/F12 medium. The
      proliferation and differentiation of cultured cells were studied by colony
      forming efficiency (CFE), immunohistochemistry staining and Western blot
      examination. RESULTS: LCs could be passaged 5 times in this culture condition.
      The CFE of stem cells was (5.07 +/- 2.35)%, while that of the central epithelial
      cells (CCs) was (1.12 +/- 0.86)%. The rates of freezing and recovery were (0.43
      +/- 0.22)% in LCs and (0.16 +/- 0.07)% in CCs. Limbal stem cells could be
      stimulated to proliferate better by EGF at the concentration of 5 and 20 ng/ml.
      The staining of keratin 3 (K3) to stem cells in the primary culture was negative,
      but positive in the second and third passages. However, the expression of K3 by
      Western blot examination was positive in the primary and second passages but
      negative in the fourth one. CONCLUSION: It is better for limbal stem cells to be
      used for transplantation and drug screening in the primary culture.

PMID- 11835768
TI  - [An experimental study of anti-angiogenesis with a cartilage-derived inhibitor].
AB  - OBJECTIVE: To evaluate the efficacy of a cartilage-derived inhibitor for the
      treatment of corneal neovascularization in vivo. METHODS: A cartilage-derived
      inhibitor (CDI) from bovine scapula was purified to homogeneity. By rabbit
      corneal neovascularization (CNV) model, the effect of inhibition of CDI under
      various conditions was determined in corneal micropocket analysis. RESULTS: The
      purified CDI could inhibit strongly the growing speed and area of rabbit CNV
      compared to control (P < 0.001). CONCLUSION: It is demonstrated that CDI is a
      potent dose-dependent inhibitor of angiogenesis.

PMID- 11835769
TI  - [Experimental studies on the effect of the immunosuppressant FK-506 on
      penetrating keratoplasty rejection model in rats].
AB  - OBJECTIVE: To study the immunosuppressive effects of FK-506 on allogeneic
      transplantation in a rat model. METHODS: Inbred strain Lou rats were used as
      recipients, and F344 rats were used as donors. Subconjunctival injection of FK
      506 0.1 mg/kg and cyclosporine A (CsA) 3 mg/kg were administered respectively for
      2 weeks, and the grafts were inspected by clinical evaluation. RESULTS: The group
      receiving FK-506 had a significant delay in allograft rejection with mean
      survival time (22.1 +/- 5.17) days vs. (18.4 +/- 1.4) days for the CsA group and
      (12.1 +/- 2.13) days for the control group (P < 0.01). CONCLUSION: It is
      indicated that FK-506 would be a useful drug to suppress corneal graft rejection.

PMID- 11835770
TI  - [The apoptosis and proliferation after photorefractive keratectomy].
AB  - OBJECTIVE: To search the correlation between the apoptosis and proliferation of
      keratocytes and investigate the influence of phototherapeutic keratectomy (PTK)
      and mechanical epithelial scrape (MES) on keratocyte apoptosis and proliferation.
      METHODS: Rabbit corneas received photorefractive keratectomy (PRK, -9.9 diopters,
      6 mm diameter). Animals were evaluated subsequently up to 6 months after surgery
      by in vivo confocal microscopy. Corneas were prepared for H.E. staining, corneal
      cell apoptosis was evaluated by terminal deoxyribonucleotidyl transferase
      mediated dUTP nick end labeling (TUNEL) to detect DNA fragmentation. RESULTS:
      Loss of keratocytes and keratocyte death were found anteriorly in the remaining
      stroma at 4h after PRK. Activated keratocytes observed by confocal microscopy
      repopulated within 1 month. A significant elevation of apoptosis was detected in
      keratocytes and epithelium at 4h, 3d, 1m after PRK. The level of keratocyte
      apoptosis was parallel to the loss of keratocytes at the early stage and was
      correlated with keratocyte proliferation in the later stage, PTK-PRK was
      associated with lower levels of central corneal apoptosis and activated
      keratocytes than MES-PRK. CONCLUSION: It is suggested that the loss of
      keratocytes and keratocyte apoptosis be correlated with keratocyte activation and
      proliferation, which may result in haze and regression after PRK, and PTK-PRK
      induce lower level of early keratocyte apoptosis and late keratocyte activation
      than MES-PRK.

PMID- 11835771
TI  - [Application of perfluorocarbon liquids in vitrectomy].
AB  - OBJECTIVE: To popularize the use of perfluorocarbon liquids in vitrectomy and
      increase the cure rate of complicated retinal detachment. METHODS: The clinical
      application of perfluorocarbon liquids during vitrectomy for complicated retinal
      detachment of 76 eyes has been summarized. The postoperative retinal detachment
      rate and visual acuity of 54 eyes with retinal detachment complicated with severe
      proliferative vitreoretinopathy and 11 eyes with giant retinal tears were
      analyzed statistically. RESULTS: The retina was reattached in 71 of 76 eyes
      (93.4%), in 50 of 54 eyes with severe PVR (92.6%) and in 9 of 11 eyes with giant
      retinal tears (81.8%). The postoperative visual acuity was above 0.02 in 69 eyes
      (90.8%) and > 0.1 in 29 eyes (38.2%) of 76 eyes, respectively in 50 (92.6%) and
      18 (33.3%) of 54 eyes with severe PVR and 9 (81.8%) and 4 (36.4%) of 11 eyes with
      giant retinal tears. During surgery, perfluorocarbon entered through tears into
      subretinal space and was removed immediately in 6 of 76 eyes. Postoperatively, a
      small portion of residual perfluorocarbon liquid was observed in the anterior
      chamber of 17 of 76 eyes and in the vitreous cavity of 2 phakic eyes of 76 eyes,
      no complication was observed except one case with mild corneal opacification.
      CONCLUSION: Perfluorocarbon liquids are the useful adjunct to the hydrokinetic
      manipulation in vitreous surgery.

PMID- 11835772
TI  - [A study on expressions of P53 protein and proliferating cell nuclear antigen in
      malignant eyelid tumors].
AB  - OBJECTIVE: To observe the relationship between P53 gene mutation and malignant
      eyelid tumor. METHODS: The expressions of P53 protein and proliferating cell
      nuclear antigen (PCNA) in 102 cases with malignant eyelid tumors were examined by
      labelled streptravidin biotin (LSAB) immunohistochemical technique. RESULTS:
      Although overexpression of P53 protein was not detected in normal eyelid
      cutaneous epithelium, meibomian gland and mild epithelial dysplasia, the positive
      rate of P53 increased in degree in moderate and severe dysplasia, carcinoma in
      situ and invasive tumors, and PCNA labeling index (PI) progressively increased
      too. Overexpression of P53 protein was detected in 30/53 cases of basal cell
      carcinoma (BCC), 16/32 cases of squamous cell carcinoma (SCC), 10/17 cases of
      meibomian gland carcinoma, and the intensity of P53 protein immunostaining
      increased with the lowering in the degree of histological differentiation. The
      mean PCNA labeling index was 38.1 +/- 31.1, 38.3 +/- 30.1, 42.6 +/- 32.0
      respectively in BCC, SCC and meibomian gland carcinoma. The PI value in tumor
      tissue with positive P53 protein expression was higher than that in tissues with
      its negative expression (P < 0.05). CONCLUSIONS: The gene mutation of P53 protein
      might play an important role in the pathogenesis of malignant eyelid tumors, it
      may be one of the factors that can lead to abnormal hyperactivity of cell
      proliferation and it possibly can be a malignant sign in the progression of a
      tumor.

PMID- 11835773
TI  - [Measurement and research of posterior chamber intraocular lens tilt and
      decentration in vivo].
AB  - OBJECTIVE: To observe the situation of implanted lenses in vivid eyes and
      postoperative visual acuity affected by the lens tilt and decentration. METHODS:
      64 eyes underwent extracapsular cataract extraction with posterior chamber lens
      implantation. Postoperatively, the lens tilt was measured by means of the 3(rd)
      and 4(th) Purkinje images, and the decentration of lenses was measured on the
      anterior segment photographs taken with a fundus camera. RESULTS: The mean tilt
      was (6.95 +/- 2.46) degree, and the mean decentration, (0.66 +/- 0.28) mm. There
      were a significant differences in the tilt and decentration between the
      symmetrical bag/bag and asymmetrical bag/sulcus group (P < 0.001). Bag/bag group
      without tear had less average decentration 0.32 mm. When tilt was more than 9.65
      degrees and decentration was more than 1.02 mm, the symptom such as glare or
      monocular diplopia was obvious. CONCLUSIONS: These results indicate that in the
      bag without tear, the lenses have a perfect stability and consistent centration,
      and the tilt and decentration of the implanted lens affect postoperative visual
      quality in varying degrees.

PMID- 11835774
TI  - [Evaluating retinal nerve fiber layer by scanning laser ophthalmoscopy].
AB  - OBJECTIVE: To evaluate the efficiency of scanning laser ophthalmoscopy (SLO) on
      detecting retinal nerve fiber layer defects (RNFLD). METHODS: 95 eyes with
      primary open angle glaucoma, 37 ocular hypertension, 83 glaucomatous suspect and
      34 normal eyes were investigated by SLO to evaluate the retinal nerve fiber layer
      (RNFL). Recording tapes of 68 eyes were re-investigated by two investigators for
      estimating the intra- and inter-observer agreement. RESULTS: The intra- and inter
      observer agreement of the presence and types of RNFLD was fairly good (Kappa
      values were 0.66 - 0.76 and 0.59 - 0.65 respectively). The sensitivity and
      specificity in detecting RNFLD by SLO were 80.0% and 94.1% respectively.
      CONCLUSION: The evaluation of RNFL by SLO is a quick, accurate and safe method.
      It may be clinically useful in the diagnosis of glaucoma.

PMID- 11835775
TI  - [The extracellular matrix of optic nerve head in normal human adult].
AB  - OBJECTIVE: To demonstrate the macromolecular components of extracellular matrix
      of lamina cribrosa from young human donors. METHODS: Immunoperoxidase (ABC)
      staining method was used to investigate the distribution of collagen type IV,
      laminin and fibronectin in the lamina cribrosa of 7 pairs of normal human eyes.
      RESULTS: There was a large amount of collagen type IV and laminin in the cribrosa
      plates, but no positive staining of fibronectin in them. The positive staining of
      fibronectin only existed at the blood vessel region. CONCLUSION: The lamina
      cribrosa contains a specialized extracellular matrix of the central nerve system
      made up of plates of material resembling basement membrane.

PMID- 11835776
TI  - [The study of ultrastructure of retinal pigment epithelium of transplantation].
AB  - OBJECTIVE: To investigate the ultrastructure of retinal pigment epithelium (RPE)
      for the base of clinical application. METHODS: Pigmented rabbit RPE was
      transplanted to the subretinal space of 10 unpigmented rabbits by internal route.
      The ultrastructure of transplanted RPE cells were observed by electron
      microscopy. RESULTS: The transplantation of RPE was successful. It was shown that
      the transplanted cells had polarity and attached to Bruch's membrane to form
      basal infoldings, and the relationships between transplanted cells and the host
      photoreceptors were also seen. CONCLUSIONS: The internal approach is a practical
      and useful method for transplantation of RPE. The transplanted RPE can vitalize,
      perform metabolism and form some normal ultrastructure.

PMID- 11835777
TI  - [A study of interferon alpha-2b as an accessory drug after glaucoma filtration
      surgery].
AB  - OBJECTIVE: To elucidate the inhibitory action of interferon alpha-2b (IFN alpha
      2b) on the cicatrization under conjunctiva and the best way to use it after
      glaucoma filtration surgery. METHODS: Immunohistochemical PAP method and image
      biological system 2000 (IBAS 2000) were utilized to quantitatively analyze the
      inhibitory effect of IFN alpha-2b on the expression of epidermal growth factor
      receptor (EGFR) of cultured calf fibroblasts; the effects of IFN alpha-2b on
      collagen contents in suture-caused cicatrization under conjunctiva and changes of
      aqueous humor protein after trabeculectomy performed on rabbits have also been
      observed. RESULTS: IFN alpha-2b reduced the expression of EGFR of cultured bovine
      fibroblasts at a dose-dependent manner. The relationship between the EGFR and the
      dosage of IFN alpha-2b is Y = 2953.8 - 554.5 lgx (r = -0.98, P < 0.01). With 4.67
      x 10(-5) micromol/L IFN alpha-2b not only reduced about 50% of the collagen in
      suture-caused cicatrization, but also significantly decreased the protein
      concentration of aqueous humour 3 and 72 hours after trabeculectomy. CONCLUSION:
      It is promising that IFN alpha-2b can be used after glaucoma filtration surgery
      to reduce excessive cicatrization with many advantages compared with
      antimetabolites.

PMID- 11835778
TI  - [An experimental study on effect of methazolamide on decreasing intraocular
      pressure in rabbits].
AB  - OBJECTIVE: To study the therapeutic effect of methazolamide on glaucoma. METHODS:
      Various doses of methazolamide were orally administered in rabbits, their effects
      on high intraocular pressures and on recovery of low intraocular pressures were
      observed. RESULTS: The high intraocular pressures were significantly decreased
      and the maintenance of low intraocular pressure was significantly prolonged by
      the oral administration of 40, 20, 10 mg/kg of methazolamide. A dose-effect
      relationship that is the reduction of intraocular pressure increases with the
      increase of the dosage administration of methazolamide could be observed.
      CONCLUSION: This study indicates that methazolamide might play an effective
      therapeutic role in glaucoma.

PMID- 11835779
TI  - [The application of chopping method for phacoemulsification of hard nucleus
      cataract].
AB  - OBJECTIVE: The study was designed to investigate the application of chopping
      method for phacoemulsification of hard nucleus cataract. METHODS: Modified stop
      and chop technique was used to emulsify the hard nucleus cataract. The degree of
      nuclear hardness in 80 eyes was grade IV. RESULTS: Postoperatively, the visual
      acuity with correction was >or= 0.9 in 76.25% at 3 months. There were mild
      corneal edema in 8 cases, moderate corneal edema in 2 cases and posterior
      capsular rupture in 1 case. CONCLUSION: The modified stop and chop technique
      enables the tenacious nuclear plate to rupture easily, thus the stress on the
      zonules and capsule can be decreased, and in the mean time the technique needs
      less phaco energy and time.

PMID- 11835780
TI  - [Phacoemulsification through a small pupil].
AB  - OBJECTIVE: To discuss the surgical techniques and attention points in
      phacoemulsification through a small pupil. METHOD: Eighty three cataracts of 77
      patients were emulsified by using non-cut pupil dilation, cystotome or diathermic
      high-frequency capsulorrhexis. RESULTS: The 66 cataracts of 83 eyes were
      emulsified by means of the above method. After the surgery, all the pupils were
      recovered to normal size (2 to 3 mm), and none of them were damaged. In 17 eyes,
      the procedure was performed after separation of synechia and excision of the
      organized membranes; after the surgery, a round pupil was obtained in 15 cases
      and an irregular pupil in 2 cases. The visual acuity at postoperative 1 month was
      >or= 0.5 in 46 eyes (55.4%) and corrected >or= 0.5 in 71 eyes (85.5%).
      CONCLUSION: After phacoemulsification through a small pupil by non-cut pupil
      dilation method, the pupil can be recovered to normal and no unfavorable reaction
      is seen.

PMID- 11835781
TI  - [Phacoemulsification with foldable intraocular lens implantation through a limbus
      tunnel incision].
AB  - OBJECTIVE: To advance and evaluate the technique and therapeutic effects of
      phacoemulsification with foldable intraocular lens implantation through a limbus
      tunnel incision. METHODS: The surgery was performed through a 3.2 limbus tunnel
      incision on 110 eyes of 103 patients with senile, complicated, congenital and
      traumatic cataracts. RESULTS: Postoperatively, the visual acuities with spherical
      correction or without correction were 0.5 or better in 90.0% of the eyes at one
      day, and 1.0 or better in 42.5%, 63.7% and 68.0% at one week, one month and three
      months respectively. The mean postoperative astigmatism was (1.00 +/- 0.68) D at
      one week and only 0.07D more than the mean preoperative one (P > 0.05). There was
      also no statistical difference between the mean preoperative astigmatism and
      postoperative astigmatism at one and three months, which were respectively (0.91
      +/- 0.55) D and (0.83 +/- 0.57) D. The mean postoperative astigmatism was almost
      the same as compared between the scleral tunnel incision and clear corneal
      incision groups. CONCLUSION: The phacoemulsification with foldable intraocular
      lens implantation through a limbus tunnel incision can reduce postoperative
      astigmatism and shorten the period of visual rehabilitation as the operation
      through a scleral tunnel or a clear corneal incision, and in the mean time the
      former method can overcome the shortages of the latter two methods.

PMID- 11835782
TI  - [Phacoemulsification and posterior chamber intraocular lens implantation in high
      myopia].
AB  - OBJECTIVE: To evaluate the therapeutic effect of phacoemulsification and
      posterior chamber intraocular lens (IOL) implantation in high myopia. METHODS:
      Phacoemulsification with implantation of a foldable IOL or a PMMA rigid IOL was
      performed on 28 eyes of 21 patients with senile, complicated or congenital
      cataracts through a 3.2 mm small scleral tunnel incision or through a 5.5 mm
      incision respectively. The average age of the patients was 51.32 years (21 - 70
      years). The mean axial length was (27.56 +/- 1.21) mm (26.00 - 33.41 mm). The
      mean keratometry was (43.38 +/- 1.36) D (42.00 - 46.54 D). The mean diopter of
      IOL was (+ 9.59 +/- 3.65) D (+ 4.00 - + 15.00 D). RESULTS: Postoperatively, the
      uncorrected or corrected visual acuity 0.5 or better at 1 day, 1 week, 1 month
      and 3 months was in 63.6%, 86.4%, 95.5% and 95.2% patients respectively; the
      patients having achieved the best visual acuity of 1.0 or better were accounted
      for 9.1%, 31.8%, 50.0% and 57.1% respectively. CONCLUSIONS: Phacoemulsification
      and the posterior chamber IOL implantation offers the advantages of rapid and
      better rehabilitation of visual acuity and more stabilization of postoperative
      astigmatism in patients with high myopia; whereas for eyes with the axial lengths
      over 30 mm, the recovery of the visual acuity was less satisfactory.

PMID- 11835783
TI  - [Vitreous surgery for intraocular lens dislocated into vitreous cavity].
AB  - OBJECTIVE: To study the way to manage intraocular lenses (IOLs) dislocated into
      vitreous cavity. METHODS: Three methods of vitreoretinal surgery were applied for
      15 cases with severe dislocation of IOL into vitreous cavity: vitreoretinal
      surgery combined with simple IOL removal in 7 cases (simple group), vitreoretinal
      surgery combined with liquid perfluorocarbon (PFCL) applied for IOL removal in 3
      cases and vitreoretinal surgery combined with IOL removal and fixation of IOL at
      ciliary sulcus in 5 cases. RESULTS: The dislocated IOLs were removed successfully
      in all cases. The preoperative visual acuities were light perception to hand
      movement. Postoperatively, the patients were followed for 3 months to 3 years. In
      the cases with ciliary sulcus fixation of IOL, all their visual acuities were
      above 20/100 and the best visual acuity was 20/25. In the 10 cases without
      fixation of IOL, the corrected visual acuities were 20/1000 to 20/50. The
      complications were retinal detachment in 1 case, slight vitreous hemorrhage in 2
      cases and temporary uveitis in 3 cases. CONCLUSION: Vitreous surgery is the best
      way for the treatment of a case with IOL severely dislocated into the vitreous
      cavity, and such an IOL should be removed. Visual acuity can be improved
      significantly by the fixation of IOL at ciliary sulcus.

PMID- 11835785
TI  - [An experimental investigation of inhibition of interferon on lens epithelial
      cell growth in vitro].
AB  - OBJECTIVE: To investigate the inhibition of alpha-interferon (alpha-IFN) and
      gamma-interferon (gamma-IFN) on rabbit lens epithelial cell (RLEC) proliferation
      in vitro and their effective concentrations. METHODS: The second and third
      passage of RLEC were used for assay. Various concentrations of alpha-IFN or gamma
      IFN were added into the culture medium and RLECs were exposed to these drugs.
      After 24 and 72 hours, the inhibition of RLECs was determined by counting the
      RLEC numbers on a counting plate and MTT colorimetric assay. RESULTS: Alpha-IFN
      and gamma-IFN may reduce the proliferation of RLECs at the concentration of 10(3)
      - 10(4) IU/ml. The inhibition of gamma-IFN was a little stronger than that of
      alpha-IFN. CONCLUSION: The experiment provides a scientific basis for selection
      of drugs to prevent after cataract.

PMID- 11835784
TI  - [Relationship between GSTM1 genotype and susceptibility to senile cataract].
AB  - OBJECTIVE: To study the relationship between the glutathione s-transferase gene
      deletion and cataract formation. METHODS: Blood cells of total of 77 cases with
      senile cataract and 76 controls were detected for GSTM1 gene, and the subcapsular
      epithelial cells of 22 cataract lenses were also detected for GSTM1 gene.
      RESULTS: The GSTM1 gene deletion rate in cataract group was 53.25% and that in
      the control group was 46.05%, they being not significantly different
      statistically (chi(2) = 0.750, P > 0.05, OR = 0.75). GSTM1 gene deletion rate in
      the subcapsular epithelial cells of 20 cases was basically consistent with that
      in blood cells. CONCLUSION: GSTM1 gene deletion is not related to senile cataract
      formation.

PMID- 11835786
TI  - [The effect of extracting lens on damage of corneal endothelium in vitreous
      surgery].
AB  - OBJECTIVE: To observe the effect of extracting lens on the damage of corneal
      endothelium in vitreous and retinal surgery. METHODS: The corneal endothelial
      cell densities of 179 eyes were observed preoperatively and at postoperative 2,
      4, 8 weeks and 3 and 6 months. RESULTS: Postoperatively, there was no significant
      change of the corneal endothelial cell densities compared with that of the
      preoperative ones in phakic eyes among different operations. There was also no
      significant change of the cell densities, but an tendency of cell loss in the
      aphakic and pseudophakic eyes after vitreous and retinal surgery. The corneal
      endothelial cell densities decreased significantly after vitrectomy with
      lensectomy. CONCLUSIONS: It is the vitrectomy with lensectomy that makes the
      corneal endothelial damage. Vitreous and retinal surgery poses a risk to corneal
      endothelium in the aphakic and pseudophakic eyes.

PMID- 11835787
TI  - [Vitrectomy for vitreous hemorrhage caused by retinal vein occlusion].
AB  - OBJECTIVE: To evaluate the efficacy and complications of vitrectomy for vitreous
      hemorrhage after retinal vein occlusion. METHODS: We retrospectively studied 47
      patients (47 eyes) having undergone vitrectomy during the period from April, 1992
      to December, 1996. Follow-up was made on 30 patients. RESULTS: (1) Visual acuity
      was improved postoperatively in 80% of the eyes. The patients with branch vein
      occlusion achieved more favorable final vision than those with central retinal
      vein occlusion (P < 0.05). (2) The most common complications were lens opacity,
      recurrent vitreous hemorrhage, iatrogenic rhegmatogenous retinal detachment and
      glaucoma. (3) Patients treated with endophotocoagulation had a lower rate of
      recurrent vitreous hemorrhage (P < 0.05). CONCLUSIONS: (1) More than half of the
      patients can achieve ambulant vision after vitrectomy for vitrous hemorrhage
      induced by retinal vein occlusion. (2) Recurrent vitreous hemorrhage can be
      effectively prevented by endophotocoagulation during the operation.

PMID- 11835788
TI  - [Timing of vitrectomy for proliferative diabetic retinopathy in cases with type
      II diabetes mellitus].
AB  - OBJECTIVE: To determine the timing of vitrectomy for proliferative diabetic
      retinopathy with severe vitreous hemorrhage, retinal traction and even tractional
      detachment resulted from fibrovascular membranes in type II diabetes mellitus.
      METHODS: According to the preoperative duration of vitreous hemorrhage and
      severity of diabetic retinopathy, 78 eyes of 64 cases having undergone vitrectomy
      were divided into 2 groups for the comparison of postoperative visual acuity.
      RESULTS: After 9 months of follow-up, in the group with preoperative vitreous
      hemorrhage of <or= 6 months' duration 42.1% of cases had visual acuity of >or=
      0.3, while in the group with preoperative vitreous hemorrhage of > 6 months'
      duration 5.3% of cases reached such a level (P < 0.01). After one year, in the
      group with preoperative vitreous hemorrhage of <or= 6 months 35.7% of cases had
      visual acuity of >or= 0.5, while in the group with preoperative vitreous
      hemorrhages of > 6 months' duration, 7.1% (P < 0.05). In the group of vitreous
      hemorrhage with or without local tractional retinal detachment, 35.7% had visual
      acuity of >or= 0.5, while in the group with large area of tractional retinal
      detachment, 16.7% (P < 0.05). CONCLUSION: Earlier vitrectomy is preferable for
      type II diabetes mellitus with vitreous hemorrhage, and the operative treatment
      should not be abandoned for the patients with vitreous hemorrhage of longer
      duration and severe tractional retinal detachment.

PMID- 11835789
TI  - [Extra-trabeculotomy and trabeculectomy in treatment of primary infantile
      glaucoma].
AB  - OBJECTIVE: To compare the effectiveness and complication of extra-trabeculotomy
      and trabeculectomy in the treatment of primary infantile glaucoma. METHOD:
      Patients with primary infantile glaucoma and having undergone either of the two
      procedures from Jan, 1992 - June, 1996 were selected. Among them, group one (30
      patients, 51 eyes) underwent extra-trabeculotomy, while group two (26 patients,
      46 eyes) underwent trabeculectomy. RESULTS: The success rates in group one were
      92.2% at the time of discharge and 87.5% during follow-up (mean 26.3 months); the
      rates in group two were 73.9% and 62.9% (mean 28.1 months) respectively, the
      differences being significant (P < 0.05). In group one, there was no severe
      complication, while in group two, two cases had vitreous prolapse. CONCLUSION:
      Extra-trabeculotomy is more efficacious and safer than trabeculectomy in the
      treatment of primary infantile glaucoma. It should be the first choice in the
      treatment of primary infantile glaucoma.

PMID- 11835790
TI  - [Observation of the anterior ischemic optic neuropathy by color Doppler flow
      imaging].
AB  - OBJECTIVE: To study the characteristics of color Doppler flow imaging (CDFI) in
      anterior optic neuropathy (AION). METHODS: Forty eyes of 25 patients clinically
      diagnosed to have progressive AION were studied by using CDFI. The peak systolic
      velocity (PSV), end-diastolic velocity (EDV), time averaged maximum velocity
      (TAMV) and resistance index (RI) of the central retinal artery (CRA), nasal and
      temporal posterior ciliary arteries (PCAs) and ophthalmic artery (OA) were
      detected. The diameter of retrobulbar optic nerve (ON) was detected at the same
      time. Thirty-four volunteers were served as the control group. RESULTS: In the
      comparison with the control group, there were significantly reduced PSV, EDV and
      TAMV in PCAs (P < 0.001) and CRA (P < 0.001) and markedly increased RI in PCAs,
      CRA and OA in AION group. The retrobulbar optic nerve edema was found in 32/40
      eyes. CONCLUSIONS: The characteristics of reduced velocity and increased
      resistance index in retrobulbar arteries of the AION are demonstrated. CDFI is
      helpful to the diagnosis of AION.

PMID- 11835791
TI  - [A clinical analysis of Mooren's corneal ulcer].
AB  - OBJECTIVE: To investigate the clinical characteristics and to compare the effects
      of several therapies of Mooren's corneal ulcer. METHODS: 550 consecutive in
      patients with Mooren's corneal ulcer were clinically analyzed, including the age,
      sex, laterality of the eye, ulcer location, rate of perforation, cure rate of
      surgeries, recurrent rate, and the effects of conjunctiva excision, lamellar
      keratoplasty (LKP), LKP plus cyclosporin A eye drops. RESULTS: The average age of
      onset of the ulcer was 48.4 years old, the ratio of male to female was 1:0.74,
      bilateral disease occurred in 165 cases (30.0%) of whom 52 cases (31.5%) were in
      the younger group and 113 (68.5%) in the older group. There were 501 eyes (70.1%)
      with the ulcer located at the limbus of palpebral fissure, and 95 out of 715 eyes
      with the disease had corneal perforation, the rate of perforation being 13.3%, 41
      cases (43.2%) in the younger group and 54 cases (56.8%) in the older group. The
      postoperative recurrent rate was 25.6%. The cure rate of once LKP plus
      cyclosporin A eye drops was 73.7%, the final cure rate was 95.6%, and the
      preservative rate of the corneal anatomical structure of the surgeries was 99.7%.
      CONCLUSION: LKP plus cyclosporin A eye drops is an effective treatment of
      Mooren's corneal ulcer.

PMID- 11835792
TI  - [Clinical analysis of orbital cysticercus cellulosae].
AB  - OBJECTIVE: To investigate the clinical features, laboratory tests, medical
      imaging manifestations, diagnosis and treatment of orbital cysticercus
      cellulosae. METHODS: 23 cases of orbital cysticercus cellulosae were analyzed
      from 1973 to 1997. RESULTS: Most cases had features of exophthalmos, lid
      swelling, limitation of ocular movement. Some of them with visual loss, optic
      papilledema and orbital mass. B-scan ultrasonography revealed a cystic tumor and
      a strong echo spot with spontaneous movement. On CT scanning, found was a well
      defined hyperdensity mass in which there was a low density area. On MRI, the
      signal intensity of T(1)WI of cystic fluid was low or moderate and of T(2)WI was
      high, while the signal intensity of T(1)WI and T(2)WI of surrounding scar tissue
      was still low. CONCLUSION: We can make diagnosis by imaging tests and treat them
      with surgical operations.

PMID- 11835793
TI  - [Clinical practice of spherical allogeneic biological membranous implant in the
      eye socket].
AB  - OBJECTIVE: To investigate the effect of implantation of spherical allogeneic
      biological material implant after eyeball enucleation. METHODS: A spherical
      allogeneic biological material implant was implanted in the eye socket after
      eyeball enucleation in 50 cases including stage I in 48 cases and stage II in 2
      cases. RESULTS: After operation, the motility of installed artificial eyes was
      good in 49 cases, the orbit and eyelids were full in all the cases. In the follow
      up of 4 - 24 months (mean, 8 months), the conjunctival wound and muscular tissue
      were adherent firmly to the biological material, and there were no postoperative
      infection, no dislocation and shift of the implant. CONCLUSION: The spherical
      allogeneic biological membranous implant is an ideal material for the
      implantation in the eye socket after enucleation.

PMID- 11835794
TI  - [Effects of epidermal growth factor, basic fibroblast growth factor and 5
      fluorouracil on human retinal pigment epithelial wound closure in vitro].
AB  - OBJECTIVE: To study the effects of epidermal growth factor (EGF), basic
      fibroblast growth factor (bFGF) and 5-fluorouracil (5-Fu) on the cell migration
      and proliferation. METHODS: Phase-contrast microscopy, cell proliferation assay
      and wound -closure were used to study the process of cell proliferation and wound
      healing in a model of human retinal pigment epithelial (RPE) cell damage.
      RESULTS: It was found that EGF mainly stimulated proliferation and the migration
      of individual RPE cells from the wound edge, and induced cellular elongation,
      while bFGF mainly promoted proliferation and spread of the confluent monolayer
      into the wound defect, and induced enlargement and flattening of cells. But the
      effects of EGF, bFGF on wound closure were not very significant; 5-Fu inhibited
      the spread and proliferation of RPE cells, but had no effects on cell migration.
      CONCLUSIONS: EGF and bFGF have no significant effects on wound-healing, perhaps
      their effects on cell morphology are very important in cell transformation in
      proliferative vitreoretinopathy (PVR), and 5-Fu can only be a subsidiary drug to
      prevent PVR.

PMID- 11835795
TI  - [Rat retinal ganglion cells in culture].
AB  - OBJECTIVE: To establish a culture system for retinal ganglion cells (RGCs) in
      order to lay a foundation for the experimental research in vitro. METHODS: The
      retinae of 16 postnatal 2 - 3 day Sprague-Dawley rats were dissected into cell
      suspension with trypsin digestion. The cell suspension was implanted in 24 well
      culture plates with a cover slide 1 cm(2) in size and covered with murine tail
      collagen preplaced in each well (4 x 10(5) cells/well) and cultured under 37
      degree C in an incubator with 5% CO(2). The cells were identified by
      immunocytochemical method with anti-rat Thy -1.1 monoclonal antibody after
      culture for 1, 3, 5 days, respectively, and the number of RGCs and its axon
      growth percentage were counted in each 10-field high power (HP, 200 x) view under
      light microscope. RESULTS: The RGCs cultured in murine tail collagen tissue grew
      very well. Some cells possessed axons and some axons connected in networks. The
      RGC number and its axon-growth percentage were (401 +/- 9) cells/10 HP and (25.34
      +/- 0.72)% in 1-day-culture, (351 +/- 6) cells/10 HP and (35.16 +/- 2.22)% in 3
      day-culture, (109 +/- 8) cells/10 HP and (69.84 +/- 0.97)% in 5-day-culture,
      respectively. CONCLUSION: RGCs can be cultured successfully and the murine tail
      collagen tissue is a good substratum for RGC survival in vitro.

PMID- 11835796
TI  - [TNF-alpha, IL-8 and IL-6 in the early inflammatory stage of experimental PVR
      model induced by macrophages].
AB  - OBJECTIVE: To observe the levels of cytokines, tumor necrosis factor-alpha (TNF
      alpha), interleukin-8 (IL-8) and IL-6 in the early inflammatory stages of a
      rabbit proliferative vitreoretinopathy (PVR) model induced by macrophages.
      METHODS: The vitreous and venous blood of rabbit eyes of the PVR model were
      obtained and tested with ELISA kits of TNF-alpha, IL-8 and IL-6 and analyzed
      statistically. RESULTS: The TNF-alpha level increased at the 7th day after
      macrophage injection and reached its peak (309 pg/ml) on day 21. IL-8 and IL-6
      maintained their higher levels during 7 to 21 days after macrophage injection and
      the peak levels were 1 325 pg/ml and 998 pg/ml on day 14 respectively. Those
      showed significant differences compared to control (P <or= 0.05). CONCLUSION: The
      3 cytokines, TNF-alpha, IL-8 and IL-6, present high levels in the early stage and
      proliferative phase of the PVR model and decrease to normal level in the
      regeneration (scarring) phase, indicating that these cytokines may play an
      important role in initiating and modulating the cellular proliferation.

PMID- 11835797
TI  - [Relationship between retinal and glomerular microvascular lesions in
      experimental diabetes in rat].
AB  - OBJECTIVE: To evaluate the relationship between diabetic retinopathy (DR) and
      diabetic nephropathy (DN). METHODS: The thickness of retinal capillary basement
      membrane (RBM) and glomerular basement membrane (GBM) and their anionic sites
      were quantitatively analyzed by electron microscopy and immunohistochemical
      methods. RESULTS: RBM and GBM became gradually thickened with the development of
      diabetes. The thickened basement membrane was accompanied with decrease of
      anionic sites in number. CONCLUSION: DR and DN share partly the pathological
      process, and there are also some incoordinate phenomena in the microvascular
      lesion.

PMID- 11835798
TI  - [Studies of the mechanism of lowering intraocular pressure on Erycibele
      alkaloid].
AB  - OBJECTIVE: To investigate the molecular pharmacological mechanism of lowering
      intraocular pressure of Erycibele alkaloid. METHODS: Rabbit pupil diameter was
      measured by a pupillary ruler in constant illumination and the intraocular
      pressure (IOP) was measured by pneumatonometer. Iris contracting force was
      measured in an experiment of isolated rabbit iris. Radioimmune method was used to
      determine the content of cyclonucleotide. RESULTS: The pD(2) value (the affinity
      to M-receptors of agonist) of Erycibele alkaloid's miosis is 3.60 +/- 0.15 and
      its IOP lowering action is 3.49 +/- 0.07. In the isolated iris contracting
      experiment, its pD(2) value is 6.38 +/- 0.12. M(3) receptor antagonist is the
      strongest antagonist in inhibiting the miosis, IOP lowering action and isolated
      iris pupillary contracting action of Erycibele alkaloid. 0.01% Erycibele alkaloid
      can cause the decrease of cAMP and the increase of cGMP in the aqueous humor.
      CONCLUSIONS: The effects of miosis and IOP lowering of Erycibele alkaloid are all
      mediated by M(3) receptor subtype and its signal transductive mechanism is
      connected with cyclic nucleotide system.

PMID- 11835799
TI  - [Comparison of results of chamber angle examination by ultrasound biomicroscopy
      and gonioscopy].
AB  - OBJECTIVE: To compare the consistency of the chamber angles examined by
      ultrasound biomicroscope (UBM) and gonioscope and provide gonioscopic examination
      with new methods and technology. METHODS: 10 patients (20 eyes) were selected for
      the research. The same eyes were examined by UBM and gonioscope in turns. The
      results from the two methods were compared and the data were analyzed with
      Spearman correlation test. RESULTS: The results of two methods of chamber angle
      examination were well consistent when the angle was wide, but the consistency was
      not good when it was narrow. The angle examined by a gonioscope was wider than
      that by UBM. When the iris root insertion was evaluated in a narrow angle, the
      consistency was also not good, and when the peripheral iris morphology was
      evaluated, there were almost inconsistent results in one-fourth of the patients.
      CONCLUSIONS: The results of chamber angle examined by a gonioscope show a little
      wider than its natural status. Especially, it is difficult to distinguish the
      functional closure from the adhesive closure. Under the influence of light, the
      determination of iris root insertion by a gonioscope has a sense of conjecture.
      When peripheral iris morphology is evaluated, the influence of irregular iris
      might result in a wrong conclusion. Therefore, the technique of gonioscopic
      examination should be improved.

PMID- 11835800
TI  - [The clinical analysis of corticosteroid ocular hypertension and corticosteroid
      glaucoma after photorefractive keratectomy].
AB  - OBJECTIVE: To inquire into the incidence, clinical characteristics and
      therapeutic effects of corticosteroid hypertension and corticosteroid glaucoma
      after photorefractive keratectomy (PRK). METHODS: The authors completed a follow
      up study on 1 590 eyes on which this procedure was performed and corticosteroid
      (0.1% fluoromethalone, FML) eye drops were applied 4 to 6 months post-operatively
      to observe intraocular pressure at 1, 3, 6, 12 and 24 months, and treated the
      eyes with increase of intraocular pressure. RESULTS: Corticosteroid ocular
      hypertension or corticosteroid glaucoma occurred in 2.70% of 1 590 eyes. The
      intraocular pressure of the eyes was recovered to normal in all patients after
      treatments of stopping FML eye drops, using topical 0.5% timolol (or 0.5%
      levobunolol hydrochloride), taking diamox orally or receiving trabeculectomy.
      CONCLUSIONS: Topical application of corticosteroid may cause corticosteroid
      hypertension and corticosteroid glaucoma after PRK, and visual function damage
      may occur in a few eyes. Under this situation, the corticosteroid eye drops
      should be stopped and glaucomatous treatment should be given.

PMID- 11835801
TI  - [Secondary glaucoma after anterior chamber intraocular lens implantation].
AB  - OBJECTIVE: To investigate the intraocular pressure level, the change of anterior
      chamber angle and the occurrence of secondary glaucoma after anterior chamber
      intraocular lens (AC-IOL) implantation. METHODS: Sixty-two AC-IOL implanted eyes
      were followed up postoperatively for 3 months to 7 years (mean 31 months). The
      examination of anterior chamber angle was emphasized. The type of cataract mainly
      included senile and traumatic. The operation performed were lensectomy with
      anterior vitrectomy or extracapsular cataract extraction (ECCE) combined with
      primary or secondary AC-IOL implantation. RESULTS: The incidence of postoperative
      peripheral anterior synechia (PAS) of iris was 87.1% and that of the secondary
      glaucoma (mainly the angle-closure) was 11.3%. The incidence of the glaucoma
      after ECCE with primary or secondary implantation was 17.4%, while that after
      ECCE combined with anterior vitrectomy was 0%. CONCLUSION: The main causes of the
      secondary glaucoma are possibly the rupture of posterior capsule and vitreous
      loss during the surgery leading to postoperative severe uveitis and pupillary
      block. To prevent its occurrence, it is important to combine ECCE with anterior
      vitrectomy.

PMID- 11835802
TI  - [Influence of transforming growth factor-beta1 on actin in cultured human
      trabecular cells].
AB  - OBJECTIVE: To understand transforming growth factor-beta(1) (TFG-beta(1))
      influencing microfilament actins in cultured human trabecular cells (HTCs) and
      approach to the effect of resistance of aqueous outflow in the pathogenesis and
      mechanism of primary open angle glaucoma (POAG). METHODS: Trabecular meshwork was
      collected from 68 eyeballs of 34 human donors under 6 years old within 24 hours
      after death. HTCs were primarily cultured and subcultured. Cultured cells were
      observed by light and electron microscopes. Laminin (LN) and IVcollagen (IVC) in
      extracellular matrix (ECM) were immunohistochemically stained by S-P method.
      Various doses (0, 1, 5 ng/ml) of TFG-beta(1) and 30 microg/ml neutralizing
      antibody of TFG-beta(1) were respectively added to the third passage cells before
      confluence and acted for 6, 12, 24 hours. Stress fibers stained with fluorescein
      isocyanate (FITC)-phalloidin were observed under light and electron microscopes.
      Various doses (0, 0.5, 1, 5 ng/ml) of TFG-beta(1) and 30 microg/ml neutralizing
      antibody of TFG-beta(1) were respectively added to the third passage cells after
      confluence for one week and acted for 6, 12, 24, 48 hours. The positive numbers
      of labeled F-actins were quantitatively evaluated by flow cytometry. Various
      doses (0, 0.5, 1, 5 ng/ml) of TFG-beta(1) and 30 microg/ml neutralizing antibody
      of TFG-beta(1) were respectively added to the third passage cells after
      confluence for one week and acted for 6, 12, 24, 36, 48 hours. The amount of beta
      actin mRNA expression was semi-quantitatively evaluated by densitometry with
      reverse transcription-polymerase chain reaction (RT-PCR) using specific
      oligonucleotide primers for beta-actin and glyceraldehyde-3-phosphate
      dehydrogenase (G3PDH) as an internal standard. RESULTS: According to the growing
      characteristics and morphological features of the cultured cells, they were
      identified as HTCs. In comparison with the control group, TGF-beta(1) could
      increase the stress fibrous bundle, the contents of F-actins and the expression
      of beta-actin mRNA; the effects of TFG-beta(1) appeared time dependent and were
      antagonized by neutralizing antibody of TFG-beta(1). When TFG-beta(1) was at
      higher concentration and longer acting time, cell proliferation was inhibited,
      cell membrane ruptured and cells peeled off in cultured HTCs before confluence.
      CONCLUSIONS: Application of reverse transcription-semiquantitative PCR can
      promote the pathogenic research of POAG at genetic level, in a certain extent,
      TFG-beta(1) can obviously upregulate microfilament actins in the confluent HTCs,
      enhance the contractility of trabecular cells and decrease the resistance of
      aqueous outflow in trabecular meshwork.

PMID- 11835804
TI  - [Diagnosis and analysis of cyclodialysis by ultrasound biomicroscopy].
AB  - OBJECTIVE: To determine the morphologic changes and their clinical significance
      of cyclodialysis. METHODS: 173 eyes of 173 patients with cyclodialysis were
      examined by ultrasound biomicroscopy (UBM) for the morphologic changes, and the
      measurements of relative parameters were analyzed statistically. RESULTS: The
      cyclodialysis in all the cases was 360 degree. The characteristic manifestations
      of cyclodialysis found by UBM were as follows: no echoes between sclera and
      ciliary body, anterior displacement and rotation of ciliary process and
      displacement of pars plana toward the centre of eyeball. Superciliary effusion
      could be observed in some cases. In some patients, the ciliary body may be
      completely disintegrated from the scleral spur, but the disintegration may be
      quadrantal instead of 360 degree, resulting in a fistula between anterior chamber
      and superciliary cavity. The anterior chamber depth of the affected eye (2,115 +/
      589) microm was markedly shallower than that of the normal eye (2,736 +/- 441)
      microm (t = 4.49, P < 0.001). The shallowing of anterior chamber was caused by
      the anterior displacement and rotation of ciliary processes and the resulting
      anterior bulging of the iris root. CONCLUSIONS: UBM can be used to make a correct
      diagnosis of cyclodialysis irrespective of optic media condition, and can provide
      evidences for treatment.

PMID- 11835803
TI  - [The experimental research of purification and character of cultured retinal
      ganglion cell].
AB  - OBJECTIVE: To establish a cell line and purification model of retinal ganglion
      cells (RGCs) in vitro. METHOD: RGCs from Sprague Dawley neonatal rats (postnatal
      1 - 3 days) were cultured in basal medium eagle (BME) basal medium. The growth
      regularity of RGCs in vitro was observed under phase-contrast microscope. RGCs
      were purified by Thy 1.1 with FITC antibody and detected under fluorescent
      microscope and phase-contrast microscope. RESULTS: Higher density of retinal
      cells and tectal extract facilitate cultured RGCs to survive. The purification
      rate of retinal ganglion cells in the experiment arrived at 95 percent.
      CONCLUSION: Cytokine and trophic factors from other cells in the retina and
      tectal extract can promote RGCs to survive, and they can be purified by Thy 1.1
      antibody.

PMID- 11835805
TI  - [Digital subtraction angiography of cerebrum for diagnosis of cavernous sinus
      fistula and its intravascular treatment].
AB  - OBJECTIVE: To evaluate the diagnosis of digital subtraction angiography (DSA) of
      cerebral arteries and the intravascular treatment for carotid artery-cavernous
      sinus fistula (CCF) mainly manifesting as pulsating exophthalmos. METHODS:
      Digital subtraction angiography (DSA) of cerebral arteries was carried out for 15
      patients with pulsating exophthalmos. Of them, detectable balloon and tungsten
      filament microcoil were used for intravascular embolism treatment in 12 cases,
      and the 3 cases with CCF of the branch of external carotid artery were not
      treated. RESULTS: Of the 15 cases, 12 were fallen in the CCF of high flow type of
      unilateral internal carotid artery, and 3 in the CCF of low flow type of
      unilateral external carotid artery. The symptoms and signs of intravascular
      embolism disappeared after treatment in 11 cases. CONCLUSION: Cerebral artery DSA
      and intravascular therapy are the ideal methods for the diagnosis and treatment
      of CCF mainly manifesting as pulsating exophthalmos.

PMID- 11835806
TI  - [Analysis of MRI and CT manifestations of paranasal sinuses and orbitocranial
      disorders with secondary exophthalmos].
AB  - OBJECTIVE: To study the MRI and CT manifestations of paranasal sinuses and
      orbitocranial disorders with secondary exophthalmos. METHODS: MRI and CT scans of
      51 patients were examined. RESULTS: MRI offers more information for evaluation of
      soft tissue lesions; the cavernous hemangioma and dermoid cyst were found to
      present rather characteristic images. Whereas in evaluation of lesions involving
      bony structures and calcifications, CT was superior to MRI. CONCLUSION: CT and
      MRI may evaluate the tumor location, extension into adjacent areas and are
      valuable in differential diagnosis of paranasal sinuses and orbitocranial
      disorder with secondary exophthalmos.

PMID- 11835807
TI  - [Retreatment after excimer laser photorefractive keratectomy].
AB  - OBJECTIVE: To evaluate the efficacy and safety of reoperation of residual myopia
      because of regression, undercorrection with or without coexisting severe corneal
      haze after excimer laser photorefractive keratectomy (PRK). METHODS: A VISK 20/20
      excimer laser was used to treat myopia of -1.00 to -16.50 diopters (spherical
      equivalent) at corneal plane. 35 patients (51 eyes) who had residual myopia
      because of regression, undercorrection with or without coexisting severe corneal
      haze after initial PRK were retreated by using PRK and phototherapeutic
      keratectomy. RESULTS: At 12 months after retreatment, the rates of uncorrected
      visual acuity more than or equal to 10/20 or 20/20 were 82.6% and 39.1%
      respectively, 100.0% and 50.0% in myopia up to -6.00 D, 73.3% and 33.3% in myopia
      of -6.25 to -16.50 D respectively. 86.3% of eyes were within +/- 1.00 diopters of
      desired emmetropia. Corneal haze after retreatment was not greater than that
      observed after initial procedures. CONCLUSIONS: The residual myopia because of
      regression, undercorrection with or without severe corneal haze after initial PRK
      can be successfully retreated. Although the therapeutic result of retreatment of
      PRK is less successful than that of the initial procedure, retreatment appears to
      enhance it.

PMID- 11835808
TI  - [Heterophoria and effect of plus lens on it in juvenile myopes].
AB  - OBJECTIVE: To study the heterophoria and effect of plus lens on it in juvenile
      myopes. METHODS: The amount of heterophoria on near (33 cm) fixation was
      respectively determined without and with correcting spectacles, and with
      correcting spectacles combined with an additional + 1.50 D lens in 151 students
      with different refractive state. RESULTS: It was liable to have exophoria in the
      myopic group without correcting lens. The amount of exophoria declined with
      correcting lens, and it increased again when a + 1.50 D lens was added to the
      correction. CONCLUSIONS: From the viewpoint of the coordination between
      accommodation and convergence, it is indicated that juvenile myopes generally
      should wear correcting spectacles, and be careful to use plus lens.

PMID- 11835809
TI  - [Association of HLA-DQA1 and DQB1 alleles with Vogt-Koyanagi-Harada syndrome in
      Han Chinese population].
AB  - OBJECTIVE: To access the association of HLA-DQA1 and -DQB1 alleles with Vogt
      Koyanagi-Harada syndrome (VKH). METHODS: The alleles in DQA1 and DQB1 loci of
      patients with VKH matched with 50 healthy controls were subtyped by polymerase
      chain reaction-sequence specific primer (PCR-SSP) and PCR-restriction fragment
      length polymorphism (PCR-RFLP). RESULTS: DQA1 * 0301 and DQB1 * 0401 alleles were
      in close association with VKH syndrome, as compared to the controls (Pc < 10(
      7)), with the relative risk (RR) 16.47 and 88.00, respectively. The frequency of
      DQA1 * 0301-DQB1 * 0401 haplotype in patients with VKH was also significantly
      higher than that in healthy controls (78.6%, 4.0%, Pc < 10(-7), RR = 88.00).
      Among the 15 patients who were negative for the haplotype of DQA1 * 0301-DQB1 *
      0401, 7 of them were found to be positive for DRB1 * 15-DQA1 * 0102-DQB1 * 0602/3
      haplotype, with the frequency significantly higher than that in the controls
      (46.7%, 12.5%, Pc = 0.01, RR = 6.13). However, DQA1 * 0103-DQB1 * 0601 was the
      only one of the DQA1-DQB1 haplotypes with a significantly lower frequency in
      patients with VKH in comparison with that in the controls (2.9%, 24%, Pc = 0.001,
      RR = 0.09). The susceptible haplotype was not related to the clinical features.
      CONCLUSIONS: The results suggest that DQA1 * 0301-DQB1 * 0401 and DRB1 * 15-DQA1
      * 0102-DQB1 * 0602/3 be associated with the susceptibility in VKH. On the other
      hand, DQA1 * 0103-DQB1 * 0601 may play a role in resisting against VKH syndrome.

PMID- 11835810
TI  - [Protect intercellular communication of pigment epithelium after laser
      photocoagulation].
AB  - OBJECTIVE: To observe the protective effect on the intercellular communication of
      retinal pigment epithelial (RPE) cells of dexamethasone (Dex) and verapamil (Ver)
      at different concentrations after laser photocoagulation. METHOD: Ten pig eyes
      were used to culture pig pigment epithelium cells. Use different concentrations
      of Dex and Ver to incubate cultured RPE cells 2 hours before laser coagulation,
      and then measure the intercellular communication function of confluent cells
      surrounding the coagulation spots after photocoagulation. RESULT: 125 mg/L Dex
      and 20 mg/L Ver could protect the intercellular communication of RPE cells under
      laser photocoagulation. The high concentration of drugs had better result.
      CONCLUSION: Both Dex and Ver can preserve the intercellular communication in
      vitro. The protective capacity is related to the concentration of drug.

PMID- 11835811
TI  - [A study of p53 gene mutations in squamous cell carcinoma in eyes].
AB  - OBJECTIVE: To inquire into the molecular biological mechanisms of the occurrence
      of squamous cell carcinoma in eyes. METHODS: Using polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) method, we detected 63
      samples taken from 63 cases (including 36 invasive squamous carcinoma, 7
      carcinoma in situ, 20 papillomas) for 248 point mutations in p53 gene. RESULTS:
      22.2% (8/36) squamous cell carcinomas, 14.3% (1/7) carcinomas in situ were shown
      to contain the point mutation in codon 248 of p53 gene exon 7 and no point
      mutation was found in papillomas, the difference being significant (P = 0.021).
      No point mutation was in patients over 70, while in patients younger than 70, the
      mutation rate was 33.3%, the difference being significant (P = 0.24). No
      significant correlation was found between p53 gene mutations and clinical
      pathological manifestations (P > 0.05). CONCLUSIONS: p53 gene mutations play
      roles in the early stage of the development of squamous cell carcinomas, and
      there is no correlation between p53 gene mutations and clinical manifestations.
      The mutation in p53 gene is not the main cause of neoplasms in the elder persons
      after the seventh decade of life.

PMID- 11835812
TI  - [Plasminogen activator inhibitor-1 mRNA expression by the iris and lens
      epithelial cells of rabbit eye with intraocular lens implantation].
AB  - OBJECTIVE: To investigate the change of plasminogen activator inhibitor-1 (PAI-1)
      synthesized by the iris and the lens epithelial cells (LECs) after extracapsular
      cataract extraction (ECCE) with intraocular lens (IOL) implantation and the role
      of PAI-1 in the occurrence of fibrin reaction and the formation of posterior
      capsular opacification. METHODS: Eight adult rabbits were studied. In each
      rabbit, one eye underwent ECCE with IOL implantation and the other eye was normal
      without any surgical intervention. The iris tissue and the lens capsule of each
      two normal eyes and each two surgical eyes were excised on the postoperative 1,
      7, 15 and 30 days respectively. The amount of PAI-1 mRNA expression in the
      specimens was detected by using reverse transcription-polymerase chain reaction
      (RT-PCR). The data were analyzed statistically. RESULTS: The amount of PAI-1 mRNA
      expresson in the iris tissue and the LECs of the surgical eyes displayed a
      significant increase on the first day after operation. The high expression of PAI
      1 mRNA by the iris might last 15 days (P < 0.001), but it declined to the normal
      range on the postoperative 30 days (P = 0.87). The high level of PAI-1 mRNA
      expresson by the LECs in the surgical eyes had significant difference when
      compared with that of the normal eyes at 1, 7, 15 and 30 days postoperatively (P
      < 0.001). CONCLUSION: It is indicated that PAI-1 enzyme is a major cause for
      fibrin reaction after ECCE with IOL implantation, and may play critical roles in
      the development of posterior capsular opacification.

PMID- 11835813
TI  - [The status of p53 gene in the primary retinoblastoma].
AB  - OBJECTIVE: This study was designed to investigate whether development or
      progression of retinoblastoma is related with p53 gene mutation. METHODS: A total
      of 52 cases with primary retinoblastoma were investigated for p53 gene point
      mutations. To do this, entire coding sequence, including exon 2 - 11, and their
      vicinity intron sequence were examined by polymerase chain reaction-single strand
      conformation polymorphism (PCR-SSCP) analysis followed by direct genomic DNA
      sequencing. RESULTS: Only did the polymorphisms, silent mutations and variants in
      intron have been shown in p53 gene, no real p53 gene mutation was found in
      retinoblastoma no matter the tumor carried Rb gene mutation or not. CONCLUSION:
      The evidence provided here indicates that the development or progression of
      retinoblastoma is not associated with p53 gene mutation.

PMID- 11835814
TI  - [A study of expression of p53, c-myc and PCNA in retinoblastoma].
AB  - OBJECTIVE: To investigate the expressions of p53, c-myc (oncogene) and
      proliferating cell nuclear antigen (PCNA) in retinoblastoma (Rb) and the
      relationships of the expression to the degree of differentiation and optic nerve
      infiltration. METHOD: The expressions of p53, c-myc and PCNA in Rb tissues of 31
      cases were analyzed by using LSAB immunohistochemical method. RESULTS: The
      positive rates of p53, c-myc and PCNA in Rb were respectively 51.6%, 45.2% and
      67.7% and all the expressions were significantly related to the differentiation
      degree of Rb (all P < 0.05). The expression of PCNA was significantly related to
      the optic nerve infiltration of Rb (P < 0.05). Both the expressions of p53 and c
      myc in Rb were markedly correlated with the expression of PCNA (all P < 0.05).
      CONCLUSIONS: The occurrence of Rb is the result of multiple gene mutations. The
      determinations of p53, c-myc and PCNA are of significance for evaluating the
      histologic characteristics and biological behavior of Rb.

PMID- 11835815
TI  - [A clinicopathological study of 297 cases of retinoblastoma].
AB  - OBJECTIVE: To find a morphological criterion of classification for choroidal
      invasion of retinoblastoma in order to further study clinical pathology of
      retinoblastoma (Rb) under an integrate rule. METHODS: The changes of retinal
      pigment epithelium, Bruch's membrane and choroid on histopathological sections of
      primarily enucleated eyes with Rb in 297 cases were observed under a light
      microscope. RESULTS: The globe wall invasion could be morphologically divided
      into four stages (briefly pigment epithelium-choroid classification). Stage I:
      Only retinal pigment epithelium was infiltrated, the Bruch's membrane was intact.
      Stage 2.: The Bruch's membrane was destructed, but the choriocapillaries were not
      invaded. Stage 3: The invasion reached middle choroidal blood vessels close to
      the choriocapillaris in a limited scope. Stage 4: Massive choroidal infiltration
      of all choroidal layers existed and the sclera could be simultaneously involved.
      The mortality for stage 4 was 11.5% and for stage 1 to 3 was 0.4%. CONCLUSION:
      The pigment epithelium-choroid stage (PEC-stage) classification in our study can
      be used as an integrate rule to compare the invasion degree of retinoblastoma in
      different individuals and studies.

PMID- 11835816
TI  - [Histopathology studies on 8,673 cases of ocular adnexal hyperplastic lesions and
      tumors].
AB  - OBJECTIVE: To study the histopathologic classification of ocular adnexal
      hyperplastic lesions and tumors according to the histogenesis and the anatomic
      sites. METHOD: To analyze retrospectively the pathologic specimens of 8,673 cases
      of ocular adnexal hyperplastic lesions and tumors between 1961 - 1997. RESULTS:
      There were 7,265 benign cases (83.77%), and 1,408 malignant cases (16.23%).
      Classification by anatomic sites: eye lid 5,313 cases (61.26%), orbit 1,484 cases
      (17.11%) and epibulbar 1,876 cases (21.63%). Classification by histogenesis: (1)
      Primary tumor 6,679 cases: epitheliogenic 2,481 cases (37.15%), mesenchymal 753
      cases (11.27%), lympho-hematopoietic 102 cases (1.53%), neurogenic 1,542 cases
      (23.09%), congenital abnormal embryogenetic 1,767 cases (26.46%), uncertain
      resource tumor 34 cases (0.50%). (2) Secondary tumor 13 cases; (3) Metastatic
      tumor 9 cases; (4) Non-tumor lesion 1,972 cases. CONCLUSION: The classification
      is helpful to the histopathologic diagnosis and the study about the detailed
      distribution of common ocular adnexal hyperplastic lesions and rare tumors, and
      it also increases the pathologic diagnostic data in North China.

PMID- 11835817
TI  - [Kaposi's sarcoma of eyelid and conjunctiva].
AB  - OBJECTIVE: To investigate the clinical and histopathological features of ocular
      adnexal Kaposi's sarcoma. METHODS: 12 consecutive cases of ocular adnexal
      Kaposi's sarcoma confirmed histopathologically were retrospectively analyzed from
      Ndola Central Hospital of Zambia in January, 1995-May, 1996. Histopathologic
      sections of 6 cases were reviewed. RESULTS: Among the 12 patients who were all
      young African males, the serum samples of 4 patients showed positive for human
      immunodeficiency virus (HIV) test. Most patients had acquired immunodeficiency
      virus syndrome (AIDS) related symptoms. CONCLUSIONS: Ocular adnexal Kaposi's
      sarcoma is a common ocular manifestation in AIDS and may be the first sign. It is
      classified into three stages clinically and histopathologically, that is a
      continuous process.

PMID- 11835818
TI  - [Transplantation of neural retina after photic injury of retina in mice].
AB  - OBJECTIVE: To examine the possibility of retinal photoreceptors rescued after
      photic injury by allogeneic neural retinal transplantation. METHODS: The retinal
      photic injury model was established by a light-damage trunk designed by
      ourselves. After photo-illumination, 60 mice were divided into two groups: Group
      I (n = 20) was the photic injury group and group II (n = 40), the retinal
      transplantation group; then group II was subdivided into II(A) (n = 20) and II(B)
      (n = 20) subgroups. External approach for neural retinal transplantation was
      performed at 24hr (group II(A)) and day 7 (group II(B)) after photic injury
      respectively. The recipients were sacrificed at day 6, day 12, day 18 and day 30
      post-operatively to examine whether the graft could rescue the injured retinal
      photoreceptors. RESULTS: In group I, the inner and outer segment showed edema,
      disorganization and vesiculation, the outer nuclear layer became very thin and
      disorganized, and the cell nuclear chromatin showed pyknosis and margination. In
      group II, the graft survival rate in group II(A) was 50% (10/20) and in group
      II(B) was 80% (16/20), the difference being significant (chi(2) = 3.956, P <
      0.05). Among the graft survival samples, we compared the rescue rate of
      photoreceptors between group II(A) 40% (4/10) and group II(B) 50% (8/16), the
      difference being not significant (P = 0.702). CONCLUSION: The retinal photic
      injury may result in photoreceptor degeneration that can be rescued by retinal
      transplantation, and the successful rate of the transplantation performed at day
      7 is higher than that at 24-hr after injury.

PMID- 11835819
TI  - [Observation of special stain and ultrastructure of lattice, granular and macular
      corneal dystrophy].
AB  - OBJECTIVE: To investigate the histopathological changes of lattice, granular and
      macular corneal dystrophy. METHODS: Corneal buttons were obtained from
      penetrating keratoplasty due to severe corneal dystrophy, and their sections and
      ultrathin sections with several special stains were observed under a light
      microscope (LM) and electron microscope (EM). RESULTS: In cases with lattice
      dystrophy, the stromal fusiform deposits seen under LM were confirmed to be
      amorphous materiel with filaments by EM and stained positively for Masson
      trichrome, PAS and Congo red. In cases with granular dystrophy, the granular or
      bread debris deposits found between laminae under LM were extracellular material
      observed by EM and they were stained positively for Masson trichrome and alcian
      blue. In cases with macular dystrophy, the stromal spheroid or macular deposits
      were seen under LM, and there were numerous vacuoles containing fibrils and
      granules in the cytoplasm of keratocytes and accumulative amorphous material in
      the stroma under EM; the deposits were positive for colloidal iron and alcian
      blue stain. CONCLUSION: In corneal lattice dystrophy, there are amyloid deposits;
      in granular dystrophy, there are extracellular material deposits; and in macular
      dystrophy, there is mucopolysaccharide accumulation.

PMID- 11835820
TI  - [A study on pathology and immunoglobulin of orbital tissues from cases with
      Grave's ophthalmopathy].
AB  - OBJECTIVE: To investigate pathological changes and the expression, localization
      of immunoglobulins (IgA & IgE) in orbital tissues from patients with Grave's
      ophthalmopathy. METHODS: Orbital tissues were obtained at surgery from 19
      patients with Grave's ophthalmopathy and 17 control subjects. Immunohistochemical
      studies were carried out by using anti-IgA, anti-IgE antibody and a streptavidin
      biotin-peroxidase detection system. In addition, hematoxylin-eosin, alcian blue
      and Masson trichrome stains were employed to demonstrate the pathologic changes
      in the tissues. RESULTS: 12 of 17 samples from patients exhibited IgA positive
      staining for the connective tissue associated with the extraocular muscles and
      orbicularis oculi, however only 2 control muscles reacted minimally. IgE positive
      material was found in association with the majority of leukocytes and with muscle
      fibers in 13 patients, but only 4 control subjects displayed mild reactions.
      Significant expression of IgE was more often demonstrated in patients with eye
      disease of short course than in those of longer course. CONCLUSION: These results
      support the notion that the eye muscle fiber and fibroblast are important targets
      of the orbital autoimmune reaction in Graves' ophthalmopathy in which IgA and IgE
      both play important roles.

PMID- 11835821
TI  - [The immunohistochemical changes of TGF-beta, type I and III collagen in corneal
      healing after photorefractive keratectomy].
AB  - OBJECTIVE: To observe the immunohistochemical expression of transforming growth
      factor-beta (TGF-beta), type I and III collagen in monkey corneal healing after
      photorefractive keratectomy (PRK) and find whether TGF-beta is involved in the
      process of corneal healing and correlated with the syntheses of type I and III
      collagen. METHODS: Three rhesus monkeys (6 eyes) were operated for myopic
      ablation of 10.0 diopters. The depth of ablation was 103 microm. Microscopy,
      transmission electron microscopy and immunohistochemistry were performed at 1, 3
      and 6 months after PRK. RESULTS: TGF-beta staining was positive in the epithelium
      and a few fibroblasts under the epithelium at one month after the operation. The
      staining was negative at 6 months and in the control specimens. Postoperatively,
      type I and III collagen stainings were evident at 1, 3 and 6 months. Type I
      collagen staining was positive and type III was negative in the controls.
      CONCLUSION: TGF-beta is involved in the corneal healing after PRK, and perhaps
      correlated with the syntheses of type I and III collagen.

PMID- 11835822
TI  - [Excimer laser photorefractive keratectomy for lower to moderate myopia: 5 year
      follow-up].
AB  - OBJECTIVE: To evaluate the long-term effectiveness and safety of photorefractive
      keratectomy (PRK) for patient with lower to moderate myopia. METHODS: 148 myopic
      eyes (-1.5 to -6.00 D) after PRK follow-up of more than 5 years were analyzed.
      RESULTS: Uncorrected visual acuity was >or= 1.0 in 136 eyes (91.9%), >or= 0.8 in
      4 eyes (2.7%) and >or= 0.6 in 8 eyes (5.4%). The mean spherical equivalent change
      was from (-4.43 +/- 0.97) D to (-0.12 +/- 0.22) D, and the keratometric power (K
      value) was reduced from (43.81 +/- 1.10) D to (41.36 +/- 1.30) D in the 5 years
      of follow-up (P < 0.01). CONCLUSION: The long-term effectiveness of PRK for
      myopia (-1.5 to -6.00 D) is satisfactory.

PMID- 11835823
TI  - [Clinical features of 201 cases with Duane's retraction syndrome].
AB  - OBJECTIVE: To summarize the clinical features of 201 cases with Duane's
      retraction syndrome (DRS) and discuss its differential diagnosis. METHODS: The
      201 cases in 1979 similar 1996 were retrospectively summarized. The clinical
      features including chief complaints, sex distribution, age at first visit,
      laterality, type of presentation, ocular deviation in the primary position,
      refractive errors, amblyopia, globe retraction, change of the palpebral fissure,
      upshoot and downshoot in adduction, binocular single vision, and its associated
      ocular and non-ocular anomalies were analyzed. RESULTS: There were 99 males and
      102 females with a female-to-male ratio of 1:1.65.88% of DRS cases had left eye
      involvement with two-to-one predilection for the left eye. The most common form
      of the syndrome was type 1 (184 patients, 91.54%). Exotropia was the most common
      deviation in the primary gaze (72 patients, 35.82%). Among 118 patients, most had
      abduction deficits, globe retraction in adduction, and face-turn for maintaining
      single binocular vision. Crocodile tears (26 patients, 12.93%) were the most
      frequently encountered ocular abnormality. CONCLUSIONS: Diagnosis of DRS in a
      typical case is not difficult, however, children with bilateral abduction
      deficits which may mimic DRS must be differentiated from the following four
      motility disorders, namely, abducens nerve palsy, Moebius' syndrome, congenital
      oculomotor apraxia, and congenital or infantile esotropia.

PMID- 11835824
TI  - [Effect of epidermal growth factor on proliferation of lens epithelial cells].
AB  - OBJECTIVE: To study the effect of epidermal growth factor (EGF) on lens
      epithelial cells (LECs). METHODS: Bovine LECs (bLECS) and human LECs (hLECs) in
      culture were treated with EGF. Then, MTT assay was used to examine the
      proliferation of the cells and the effect of anti-EGF receptor (EGFR) antibody.
      RESULTS: BLECs showed marked proliferation depending on the concentration of EGF
      from 10(-1) - 10(2) microg/L, and EGF at a concentration of 10 microg/L on day 3
      induced the highest increase of proliferation; EGF promoted proliferation of
      hLECs at the concentration of 1 - 10(2) microg/L and EGF of 10(2) microg/L showed
      the highest promotive effect on proliferation. The anti-EGFR antibody blocked the
      promotive effect of EGF on proliferation of hLECs when the concentration of this
      antibody was as low as 0.5 mg/L, and the blocking rate was 81% at the
      concentration of 3 mg/L. CONCLUSIONS: EGF has a promotive effect on proliferation
      of LECs. It is suggested that there are specific EGFRs on the surface of hLECs.
      EGFs bound to their receptors stimulate proliferation of LECs and play an
      important role in occurrence and development of posterior capsular opacification
      after cataract surgery.

PMID- 11835825
TI  - [Influence of cell growth factors on transferrin gene expression of human lens
      epithelial cells in culture].
AB  - OBJECTIVE: To assess the influence of transforming growth factor-beta(1) (TGF
      beta(1)) and basic fibroblast growth factor (bFGF) on the transferrin mRNA levels
      of cultured human lens epithelial cells. METHODS: Lens anterior capsules were
      collected from 40 eyeballs of 20 human donors under 3 years of age within 24
      hours after death. Lens epithelial cells were primarily cultured and subcultured.
      TGF-beta(1) (1 microg/L) and bFGF (250 microg/L) were added to the 3rd passage
      cells when they became confluent after their growth for 2 weeks. The total
      cellular RNA was extracted from cultured cells by guanidine isothiocyanate, etc.
      after the growth factors acting for 3 days. Transferrin mRNA levels were
      determined by a Northern blot analysis with a probe. RESULTS: In comparison with
      the control group, the expressions of transferrin in the growth factor treatment
      groups were obviously increased. In comparison with bFGF group, transferrin mRNA
      level in TGF-beta(1) group was obviously increased. CONCLUSIONS: TGF-beta(1) and
      bFGF upregulate transferrin gene expression of cultured lens epithelial cells
      remarkably, can reduce lenticular oxidative damaging process in which transferrin
      participates and play an important role in the pathological mechanism of cataract
      formation after extracapsular cataract extraction.

PMID- 11835826
TI  - [Surgical treatment of traumatic retinal detachment with incarceration].
AB  - OBJECTIVE: To investigate the method and effect of vitreoretinal surgery for the
      traumatic retinal detachment with retinal incarceration. METHODS: 13 eyes of
      traumatic retinal detachment with incarceration were treated by vitrectomy,
      membrane peeling, relaxed retinotomy, endophotocoagulation, intraocular
      tamponade, and in some cases scleral buckling procedure. RESULTS: The retinae
      were attached in all the cases after operation. During the follow-up period of
      three months to three years, ten eyes kept the retina attached and three cases
      suffered from recurrent retinal detachment. One of them had had a second surgical
      procedure and obtained retinal re-attachment. The anatomic result was 11/13. The
      visual acuities were improved in all the patients. CONCLUSIONS: Traumatic retinal
      detachment with incarceration is often accompanied with severe proliferative
      vitreoretinopathy. Combination of vitreoretinal surgery is an effective method
      for the lesion. Relaxed retinotomy for the incarceration is the key procedure to
      obtain the operative success.

PMID- 11835827
TI  - [Surgical management of acute retinal necrosis].
AB  - OBJECTIVE: To investigate the effects of vitreoretinal surgery in the management
      of acute retinal necrosis (ARN). METHODS: 17 cases (20 eyes) of ARN had
      undertaken the surgery, including vitreoretinal surgery for 18 eyes and scleral
      surgery for 2 eyes. 14 cases (21 eyes) of ARN patients hospitalized at the same
      period without surgery were used as controls. RESULTS: The follow-up was 5 months
      to 5 years. 15 eyes in the control group (71.4%) became phthisis bulbi. Useful
      vision remained in 17 eyes in the surgical group. CONCLUSIONS: Retinal detachment
      is still a severe complication of ARN, and proper vitreoretinal surgery can
      improve its prognosis.

PMID- 11835828
TI  - [Determination of cortisol in plasma and 24-hour urine of patients with central
      serous chorioretinopathy].
AB  - OBJECTIVE: To study the cortisol levels in patients with central serous
      chorioretinopathy (CSCR). METHODS: Endogenous cortisol levels in plasma and urine
      were determined in 44 patients with CSCR by radioimmunoassay and chromatography,
      and their results were compared with that of 41 controls. RESULTS: In acute CSCR,
      the mean values of the plasma cortisol (296.53 +/- 77.03) ng/ml and 24-hour urine
      17-hydroxysteroids (the major metabolite of cortisol metabolism) (12.08 +/- 4.82)
      mg/24 h revealed significantly higher values in the patient group (P < 0.05).
      CONCLUSIONS: Increased levels of endogenous cortisol play a role in the
      development of CSCR.

PMID- 11835829
TI  - [A study of anterior segment structures in primary infantile glaucoma eyes by
      ultrasound biomicroscopy].
AB  - OBJECTIVE: To investigate anterior segment structures in primary infantile
      glaucoma (PIG) eyes by ultrasound biomicroscopy (UBM) in vivo. METHODS: UBM high
      frequency transducer (50 mHz) was used to measure and observe the anterior
      segment of 38 PIG cases (58 eyes). RESULTS: No matter the severity of the disease
      or the age at onset, the most significant characteristics of the diseased eyes
      are relative positional changes between scleral spur and angle apex. In three
      forth of the eyes, the scleral spur lay in the lateral or posterior-lateral site
      of the angle apex and in one forth of the eyes the site of the tip of scleral
      spur was parallel with the iris root insertion. The thickness and length of
      ciliary processes in the eyes of PIG were greater than that of the normal
      infantile eyes. The ciliary processes were anteriorly displaced, pulled towards
      the lens, and part of them got into contact with the iris. CONCLUSIONS: The
      relative positional changes between scleral spur and angle apex in diseased eyes
      indicate that the poor development of scleral spur and the iris anterior
      insertion are the basic pathogenesis in PIG.

PMID- 11835830
TI  - [The significance of pattern electroretinogram in detecting retinal function in
      primary open angle glaucoma].
AB  - OBJECTIVE: To evaluate the clinical significance of pattern electroretinogram
      (PERG) in primary open angle glaucoma (POAG). METHOD: Thirty-six patients (59
      eyes) with POAG and 32 persons (59 eyes) as age-matched normal controls were
      tested by PERG. RESULTS: The changes of PERG in POAG included reduction of
      amplitudes of P(1), N(2), P(1) + N(2) and N(2)/P(1). Using the criteria of AN(2)
      + AP(1) < 2.7 and AN(2)/AP(1) < 0.7 (A = amplitude), the positive rate was 90% in
      59 eyes with POAG, and no eye from the normal control group was considered as
      abnormal. The amplitudes of PERG had already been abnormal before the early
      visual field loss occurred in POAG eyes. The amplitudes of P(1) and N(2) waves
      decreased with the enlargement of visual field defect, were positively correlated
      to the patient's visual acuity and negatively correlated to the cup/disc ratio of
      optic nerve papilla, and linear regression equations between them were
      respectively established. CONCLUSION: PERG is an useful method in detecting the
      retinal functions in POAG.

PMID- 11835831
TI  - [A study on ocular anterior segment structure after scleral buckling surgery for
      retinal detachment].
AB  - OBJECTIVE: To study the changes of the ocular anterior segment structure and the
      mechanism of angle-closure glaucoma after scleral buckling surgery. METHOD: 30
      patients (33 eyes) who suffered from rhegmatogenous retinal detachment had been
      observed before and 3 - 7 days after the surgery. The quantitative measurement of
      the ocular anterior segment structure in vivo had been done by ultrasound
      biomicroscopy (UBM). The results were statistically analyzed. RESULTS: There was
      one eye with split-like ciliary body detachment before the surgery, there were 11
      eyes with ciliary body detachment (33.3%) and the ciliary body was thickened and
      edematous after surgery. Before the surgery the thickness of the ciliary body was
      (821.32 +/- 64.21) microm and after the surgery it was (945.27 +/- 104.16)
      microm, the difference being statistically significant, P < 0.05. Parameters
      reflecting the changes of the anterior chamber angle before and after surgery
      were as follows: the anterior chamber angle became narrower, the angle open
      distance 500 decreased, the trabecular-iris angle decreased in degree, the angle
      of the scleral lateral side and iris long axis decreased, and all these
      differences were statistically significant, P < 0.05, but the depth of the
      central anterior chamber had no obvious change, and the difference was not
      statistically significant, P > 0.05. CONCLUSIONS: Ciliary body detachment and
      edema are often found after scleral buckling surgery, and post-operatively the
      central anterior chamber depth has no obvious change; ciliary body detachment and
      edema perhaps are related to the angle-closure glaucoma after the surgery.

PMID- 11835832
TI  - [Measurement of retinal nerve fiber layer thickness of normal eyes with nerve
      fiber analyzer].
AB  - OBJECTIVE: To study the retinal nerve fiber layer thickness (RNFLT) of normal eye
      and the correlation with age. METHODS: RNFLT of 198 cases of normal eyes were
      examined by using nerve fiber analyzer (NFA). RESULTS: There were significant
      inverse linear correlation between the RNFLT and age (r = -0.46, P < 0.01). In
      the analysis by the quadrant, the RNFLT was correlated with age in the superior
      and inferior quadrant. The mean ratio of superior and inferior quadrant thickness
      (S/I) was 1.041. CONCLUSION: NFA seems to be an useful tool to measure the RNFLT
      quantitatively. The RNFLT of normal eye is found to be decreased with age.

PMID- 11835833
TI  - [Data analysis on epidemiologic survey of cataract in China].
AB  - OBJECTIVE: To approach the prevalence of age-related cataract and its
      relationships with the condition of examination, diagnostic criteria and
      geographical environment in various areas. METHODS: According to the WHO's
      criteria of blindness and low vision, a statistical analysis of a national sample
      survey of blindness and low vision was carried out over the country. RESULTS: The
      number of patients with age-related cataract and visual acuity < 0.3 in both eyes
      calculated in the whole population was more than 5 million, the prevalence being
      0.46%. The prevalence of blindness and that of low vision were 0.43% and 0.58%
      respectively. Among the blind, 41.06% was caused by cataract, and the low vision
      caused by cataract was 49.38%. Among elderly of >or= 60 years, the proportion of
      the blind and low vision caused by cataract was 73.13%. When the cataract
      standard was defined as lens opacity with visual acuity < 0.7, the prevalence of
      cataract was 5.99% in Beijing sample survey at the suburb area. The incidence of
      age-related cataract in females was significantly higher than that in males. In a
      survey of Beijing suburb in 1997, the prevalence of cataract among 5,084 elderly
      people of >or= 50 years with bilateral corrected visual acuity < 0.1 was 2.22%.
      In the southern part of China, the area of low latitude, especially in the
      plateau, such as in Guangdong Province (0.69%) and in Tibet (1.04%), the
      prevalence of cataract is much higher than that in northern part, high latitude
      areas, such as Heilongjiang Province (0.26%). A comparative study of the cataract
      prevalence of elderly >or= 40 years in the areas of different levels above the
      sea and sunshine times, it shows that the higher level above the sea and longer
      sunshine time the higher cataract prevalence. CONCLUSIONS: A longer sunshine time
      and a larger amount of ultraviolet irradiation are considered as the risk factors
      of cataract. Age-related cataract is the leading cause of blindness and the low
      vision in China.

PMID- 11835834
TI  - [Prevalence of blindness among adults aged 50 years or above in Shunyi county of
      Beijing].
AB  - OBJECTIVE: To estimate the prevalence of blindness among older adults aged >or=
      50 years in Shunyi county of Beijing, China. METHODS: Cluster sampling was used
      in randomly selecting individuals aged >or= 50 years in 28 villages in Shunyi
      county in fall, 1996. The survey was preceded by a pilot study where operational
      methods were refined and quality assurance evaluation was carried out. RESULTS:
      5,555 individuals were enumerated. The response rate was 91.5%. In this
      population, the prevalence of blindness was 1.7% defined as pinhole visual acuity
      < 0.05 in both eyes; or 2.8% were blind, defined as presenting visual acuity <
      6/60 in both eyes. Blindness was associated with older age and female gender. The
      principal cause of blindness in eyes was cataract. CONCLUSIONS: The prevalence of
      blindness was decreased 35.8% after ten year active eye-care program in the
      survey area. However, cataract blindness continues as a significant problem among
      elderly, especially females, in this population sample of rural area.

PMID- 11835835
TI  - [The vision distribution and causes of blindness in elderly population in Doumen
      county].
AB  - OBJECTIVE: To investigate the vision distribution and the leading cause of
      blindness in farmer aged >or= 50 years in Doumen county. METHODS: Cluster
      sampling size was estimated within an error bound of 0.35% with 95% confidence
      limit, 1.25 design effect and 85% response rate. Presenting visual acuity was
      measured by ETDRS (early treatment diabetic retinopathy study) tumbling chart.
      Eye examinations of external eye, anterior chamber, lens, fundus and intraocular
      pressure were carried out by ophthalmologists. A diagnosis of the principal cause
      for all the eyes with presenting visual acuity less than 0.3 was made as well.
      The field survey was conducted by two teams after pilot agreement testing.
      RESULT: 5,342 individuals were examined in 36 sampling units. The prevalence of
      blindness was five-fold in the group aged >or= 70 years than in the group 50 - 59
      years. The rate of blindness in the group with less education was higher than the
      group with 5 years schooling. The leading causes of blindness were cataract
      (44.90%), cornea opacity (16.36%), globe disorders (10.76%), refractive error
      (7.08%) and glaucoma (5.88%). CONCLUSIONS: The prevalence of blindness and low
      vision was 2.67% and 19.91%, respectively in farmers aged >or= 50 years. The
      leading cause of blindness was cataract.

PMID- 11835836
TI  - [An epidemiological survey and treatment of blindness in Zhangqiu city of
      Shandong province].
AB  - OBJECTIVE: An epidemiological survey of blindness was carried out in Zhangqiu
      city of Shandong province. METHODS: According to stratified random sampling rule,
      11,884 persons were chosen as the sample (the sampling fraction is 1.27%) in the
      city. The WHO grading system for blindness was followed in the survey. RESULTS:
      The prevalence of blindness was found to be 0.31%, resulting chiefly from
      cataract (45.95%), glaucoma (24.32%) and vitreous retinal disease (13.51%). 1 016
      cases of blindness caused by cataract were operated for restoration of vision,
      that were accounted for 73.89% of all cataract blindness estimated from the
      result of the survey. The rate of intraocular lens implantation in the
      restorative operations was 84.15% (855/1,016). After operation, the corrected
      vision in 64.47% of the blindness was >or= 1.0, in 21.26% between 0.6 - 0.9, in
      10.24% between 0.3 - 0.5, and in 4.03% between 0.05 - 0.2. CONCLUSION: The
      epidemiological results show that the main cause of blindness is cataract. So it
      is the key objective for surgical restoration of vision in the prevention of the
      blindness in later days.

PMID- 11835837
TI  - [A study on visual function and quality of life in elderly population].
AB  - OBJECTIVE: To evaluate the visual impairment by visual function and quality of
      life assessment in elderly population. METHOD: All subjects aged >or= 50 years
      were identified by randomly clustering sampling. Visual Function and Quality of
      Life Questionnaire (VF/QOL) was administered by 5 interviewers for all subjects
      with presenting visual acuity less than 0.1 in at least one eye (as visual
      impairment group) and part of the subjects with presenting visual acuity better
      than 0.3 in both eyes (as control group). RESULTS: Five hundred and thirty-five
      eligible visual impairment subjects (90.8%) and 119 control subjects were
      successfully interviewed. In a 0 - 100 scores' scale, the subjective VF and QOL
      mean scores were 51.0 and 65.9 respectively. The mean score was correlated with
      age, sex and education. Mean VF and QOL scores decreased from 84.4 and 93.4 to
      14.6 and 31.2 along with the visual status worsening from normal to severe
      blindness respectively. In stepwise linear regression model, the VF and QOL
      scores were significantly correlated with age and education instead of sex.
      CONCLUSIONS: In elderly population with visual impairment, subjective visual
      function and quality of lift status are deteriorated substantially. Their scores
      are significantly correlated with age and education.

PMID- 11835838
TI  - [Analysis of intraocular pressure and corneal thickness after laser in situ
      keratomileusis].
AB  - OBJECTIVE: To analyze the changes and relationship of the intraocular pressure
      (IOP) and the corneal thickness (CT) after laser in situ keratomileusis (LASIK).
      METHODS: This prospective study comprised two groups: noncontact tonometer group
      221 eyes (156 patients) 1 month after LASIK and 72 eyes (50 patients) 3 months
      after LASIK; Goldmann applanation tonometer group 60 eyes (36 patients) 1 month
      after LASIK. The spherical equivalent, the corneal thickness and the IOP readings
      were measured pre- and post-LASIK. RESULTS: The CT was thicker than the predicted
      value and it was much more prominent in the higher myopic group with more
      regression degree of refraction. The CT at postoperative 3 month was thicker than
      that at 1 month. There was a statistical decrease in mean tonometer readings,
      both with non-contact tonometer and Goldmann applanation tonometer; and there was
      statistically significant correlation between the changes of central corneal
      thickness and the changes of non-contact tonometer readings (r = 0.2, P < 0.002).
      The IOP decrease with Goldmann applanation tonometer was less than that with
      noncontact tonometer. CONCLUSIONS: The actual ablation depth of cornea is lower
      than the predicted. The IOP readings of the patients after LASIK are lower than
      the real IOP values. Further efforts should be made to improve the accuracy.
      Goldmann applanation tonometer is a better choice measuring IOP after excimer
      photoablative corneal refractive surgery.

PMID- 11835839
TI  - [The complications of excimer laser in-situ keratomileusis for myopia].
AB  - OBJECTIVE: To analyze the complications of excimer laser in-situ keratomileusis
      (LASIK) for myopia, investigate the causes and discuss the prevention of these
      complications. METHODS: The SCMD microkeratome and Schwind Keratom F excimer
      laser were used to correct myopia on 1,265 eyes in 662 cases. The eyes were
      divided into 3 groups: A: <or= -6.00 D in 726 eyes; B: -6.25 to -10.00 D, 287
      eyes; C: > -10.00 D, 252 eyes. All of them were followed up for a period of 12
      months. RESULTS: Intraoperative corneal disk completely detached: 6 eyes (0.5%);
      corneal disk incomplete sectioned: 3 eyes (0.2%); corneal epithelial disk: 2 eyes
      (0.2%); corneal interface minute foreign metal bodies: 11 eyes (0.9%);
      postoperative steroid intraocular hypertension: 21 eyes (1.7%); macular
      hemorrhage: 2 eyes (0.2%). At postoperative 3 months, there was refractive
      regression > 1.00 D in 0.0%, 3.1% and 7.9% respectively in the 3 groups; the
      increase in astigmatism > 1.00 D, 0.4%, 2.8% and 4.4% respectively. CONCLUSION:
      LASIK is a safe effective method for correcting myopia. Yet attention should be
      paid on the complications during and after operation. With the improvement in
      operative technique and better designed procedure, these complications can be
      decreased and the preoperative correctness in estimation of the postoperative
      results and the postoperative accuracy in the correction of myopia can be
      elevated.

PMID- 11835840
TI  - [A clinical observation of krypton yellow laser photocoagulation for cystoid
      macular edema in nonproliferative diabetic retinopathy].
AB  - OBJECTIVE: To evaluate the clinical effects of krypton yellow laser
      photocoagulation for cystoid macular edema (CME) in nonproliferative diabetic
      retinopathy (NPDR). METHODS: 52 eyes (37 cases) with CME in NPDR were treated
      with local or grid macular krypton yellow photocoagulation, and according to the
      course they were divided into two groups: group I (<or= 6 months) and group II
      (>or= 7 months). The follow-up was 1 year. The visual acuity and the degree of
      macular edema in various period were analyzed and compared. RESULTS: The mean
      visual acuity was 0.27 +/- 0.21 before treatment and 0.53 +/- 0.26 after
      treatment (P < 0.01), 90.4% was increased, 5.8% was stable and 3.8% was
      decreased. CME disappeared completely in 55.8% of the patients, disappeared
      partially in 42.3% and stable in 1.9%. In group I the visual acuity was improved
      in 81.5% of the patients at post-treatment 1 month; at post-treatment 6 months,
      the visual acuity was increased in 100% of the cases, CME disappeared completely
      in 70.4% and disappeared partially in 29.6%. In group II, the visual acuity was
      improved in 20% of the patients at post-treatment 1 month, and at post-treatment
      6 months in 88%, CME disappeared completely in 40% and disappeared partially in
      56%. The differences in the rate of visual recovery and therapeutic effects
      between the two groups were statistically significant (P < 0.01). CONCLUSIONS:
      Krypton yellow laser is prominently effective and selective for CME in NPDR. The
      effects are related to the course of the disease, and the therapeutic results are
      better in cases receiving early treatment.

PMID- 11835841
TI  - [Long-term effect of extra-trabeculectomy in treatment of congenital glaucoma].
AB  - OBJECTIVE: To assess the long-term effect of extra-trabeculectomy in treatment of
      congenital glaucoma. METHODS: 29 patients (47 eyes) with congenital glaucoma
      having undergone extra-trabeculectomy were followed up for over 5 years. RESULTS:
      Success rates after single surgery were 70.2% at 6 months, 63.8% at 12 months,
      57.5% at 18 months and 55.3% at 24 months. Re-elevation of intraocular pressure
      (IOP) all happened within 2 years after surgery. 14 eyes underwent second
      trabeculectomy, and 7 eyes (50.0%) were successful the total success rate was
      70.2%. The naked visual acuity of 12 eyes (36.0%) among successful eyes was >or=
      0.5. All the diseased eyes were myopic (-0.50 to -25.00 D). CONCLUSION: Follow-up
      of trabeculectomy should be emphasized within 2 years after surgery. Ametropic
      and anisometropic amblyopia should be corrected promptly after surgery.

PMID- 11835842
TI  - [Clinical significance of preoperative B-ultrasonography for traumatic cataract].
AB  - OBJECTIVE: To approach the clinical significance of B-ultrasonography in
      detection of the break of posterior lens capsule in traumatic cataract. METHODS:
      30 patients (30 eyes) of traumatic cataract underwent preoperative B
      ultrasonography and intraoperative microscopic examination to evaluate the status
      of posterior lens capsule. RESULTS: 14 eyes showed posterior lens capsule
      unbroken in B-ultrasonography. Of them, 12 eyes were confirmed by surgery. 16
      eyes showed rupture of the posterior lens capsule in B-ultrasonography. Among
      them 14 eyes were confirmed by surgery and in 2 eyes there was no break at the
      posterior lens capsule. CONCLUSIONS: B-ultrasonography for preoperative traumatic
      cataract is harmless, painless, simple in operative procedure and accurate, thus
      it can be used as a routine examination to show the status of posterior lens
      capsule in traumatic cataract.

PMID- 11835843
TI  - [Confocal scanning laser Doppler retinal flowmetry in normal eyes].
AB  - OBJECTIVE: To introduce a new noninvasive equipment to measure the blood flow of
      optic nerve head and retina. METHODS: The scanning laser Doppler retinal
      flowmeter (Heidelberg Engineering, Heidelberg, Germany) was used to measure the
      blood flow of optic nerve head and retina of 82 eyes of 48 normal individuals.
      RESULTS: The average blood flow volume, blood flow velocity and the erythrocyte
      flow velocity of the vessel in optic nerve head were 203.14 +/- 74.77, 6, 272.43
      +/- 2,260.07, 13.14 +/- 2.58 respectively; they were 26.36 +/- 14.74, 467.99 +/-
      270.15, 1.93 +/- 1.07 in lamina cribrosa; 22.90 +/- 11.32, 514.53 +/- 370.21,
      1.69 +/- 1.12 in the temporal rim of papilla; 21.77 +/- 9.83, 493.21 +/- 290.29,
      1.65 +/- 0.90 in nasal rim of papilla; 32.55 +/- 13.00, 558.63 +/- 293.45, 1.78
      +/- 0.83 in the temporal juxtapapillary retina; 20.61 +/- 8.92, 358.64 +/-
      212.66, 1.20 +/- 0.66 in the nasal juxtapapillary retina; 28.89 +/- 11.52, 497.97
      +/- 278.70, 1.64 +/- 0.83 in the avascular area of temporal retina; 25.00 +/-
      8.04, 455.87 +/- 203.65, 1.55 +/- 0.64 in the avascular area of nasal retina.
      CONCLUSIONS: Confocal laser scanning Doppler retinal flowmetry, which is based on
      confocal laser scanning technology and Doppler flowmetry, is an effective
      clinical method to determine the blood flow in optic nerve head and retina.

PMID- 11835844
TI  - [Expression and significance of human leukocyte antigen DR and intercellular
      adhesion molecule-1 in normal and pathological corneas].
AB  - OBJECTIVE: To study the expression of human leukocyte antigen DR (HLA-DR) and
      intercellular adhesion molecule-1 (ICAM-1) in normal and pathological corneas and
      their significance in corneal inflammation and rejection after keratoplasty.
      METHODS: The expression of HLA-DR and ICAM-1 were detected in 10 normal corneas
      and 48 pathological corneas by using immunohistochemical techniques. RESULTS: HLA
      DR and ICAM-1 were not expressed or only slightly expressed in normal corneas and
      markedly expressed in pathological corneas, especially in inflammatory corneas.
      In general, HLA-DR and ICAM-1 were co-expressed in similar regions. The
      expression rates of HLA-DR and ICAM-1 in the 7 cases of keratoplasty rejection
      were higher than that in the 21 cases of non-rejection. CONCLUSION: The
      overexpression of HLA-DR and ICAM-1 is related to corneal inflammation and can
      promote the occurrence of keratoplasty rejection.

PMID- 11835845
TI  - [The PCNA immunohistochemical study of pterygium].
AB  - OBJECTIVE: To study the proliferating status of pterygium and the drug's
      influence on it. METHOD: Fifty four patients with pterygium were randomly
      assigned into three groups: Before the surgical excision of the pterygium, group
      1 (18 cases) had received no drug, group 2 (16 cases) received local
      dexamethasone treatment, and group 3 (20 cases), local homoharringtonine and
      dexamethasone treatment. The immunohistochemical study on proliferating cell
      nuclear antigen (PCNA) was performed on the surgical specimens of the pterygium.
      RESULT: The PCNA positive rate was (11.53 +/- 3.62)% in the untreated group,
      (10.28 +/- 4.18)% in the dexamethasone group (P > 0.05), and (5.59 +/- 3.82)% in
      the homoharringtonine and dexamethasone group (P < 0.01). The PCNA positive rate
      was higher in the younger patients (< 60 years) with progressive type of the
      disease than that in the elder patients (>or= 60 years) with quiet type.
      CONCLUSIONS: There are cell proliferation and PCNA expression in pterygium. The
      homoharringtonine and dexamethasone local injection before the excision of
      pterygium can effectively decrease the PCNA expression and recurrence rate of
      pterygium. Local injection of dexamethasone before surgical excision has no
      influence on the PCNA expression of pterygium.

PMID- 11835846
TI  - [Transforming growth factor-beta1 induced cultured human trabecular cells to
      produce elastin].
AB  - OBJECTIVE: To understand transforming growth factor-beta(1) (TGF-beta(1))
      inducing cultured human trabecular cells (HTCs) to produce elastin and to
      approach the effect of resistance of aqueous outflow in the pathogenesis and
      mechanism of primary open angle glaucoma (POAG). METHODS: Trabecular meshwork's
      specimens were collected from twelve normal eyeballs of six human donors under
      six years of age within 24 hours after death. HTCs were primarily cultured and
      subcultured. Cultured cells were observed under light and electron microscopes.
      Laminin (LN) and IV collagen (IV C) in extracellular matrix (ECM) were
      immunohistochemically stained by S-P method. The third passage confluent cells
      after two weeks were divided into three groups: control group, TGF-beta(1) group
      and neutralizing antibody of TGF-beta(1) group. Concentration of neutralizing
      antibody of TGF-beta(1) was 30 microg/ml. After culturing for two weeks, elastin
      in the media of three groups was respectively determined by western blotting from
      sodium dodecylsulfate-polyacrylamide gel electrophoresis using anti-human aortic
      alpha-elastin rabbit serum, biotin conjugated goat anti-rabbit IgG and anti
      biotin conjugated horse radish peroxidase. RESULTS: Cultured HTCs were identified
      from cultured cell's growing characteristics, morphological features under light
      and electron microscopes, and stained peculiarities of LN and IV C in ECM. With
      western blotting, elastin in the control group was not detected, elastin in TGF
      beta(1) group was detected, and elastin in neutralizing antibody of TGF-beta(1)
      group was not detected. CONCLUSION: TGF-beta(1) induces cultured HTCs to produce
      elastin, which the neutralizing antibody of elastin can antagonize; the increase
      of the amount of elastin may aggravate its stacking in ECM and increase the
      resistance of aqueous outflow in trabecular meshwork, leading to the occurrence
      of glaucoma.

PMID- 11835847
TI  - [Relationship between the prognosis of retinal detachment in emmetropic eyes and
      vitreous changes].
AB  - OBJECTIVE: To study the relationship between surgical prognosis of retinal
      detachment (RD) in emmetropic or myopic eyes and vitreous changes. METHODS:
      Postoperatively, 1,294 eyes of 1,262 patients with rhegmatogenous RD including
      243 emmetropic and 1,031 myopic eyes were retrospectively studied. The affects of
      proliferative vitreoretinopathy (PVR), posterior vitreous detachment (PVD),
      vitreous liquefaction and concentration on the surgical prognosis were evaluated.
      RESULTS: The cure rate in emmetropic group (88.5%) was lower than that in myopic
      group (93.8%, P < 0.01). Also, the cure rate by initial surgery in emmetropic
      group (65.4%) was lower than that in myopic group (76.4%, P < 0.01). In addition,
      the occurrences of PVD (39.6%) and liquefaction (76.1%) in emmetropic group were
      lower than that in myopic group (51.7%, and 81.8% respectively, P < 0.05).
      However, focal vitreous concentration in emmetropic group (56.8%) was much higher
      than that in myopic group (19.6%, P < 0.01). CONCLUSIONS: The surgical prognosis
      of RD especially by initial operation is worse in emmetropic group than that in
      myopic group. The lower occurrences of PVD and liquefaction but higher occurrence
      of focal vitreous concentration in emmetropic eyes may have impact on the
      prognosis. It is possible that the vitreous characteristics in emmetropic eyes
      with RD have relationship to the occurrence and development of PVR that has the
      influence on the prognosis to some extent.

PMID- 11835848
TI  - [Wavelength selection in management of central serous chorioretinopathy].
AB  - OBJECTIVE: To compare the effects of three kinds of laser wavelength in
      management of central serous chorioretinopathy (CSCR). METHOD: 89 patients with
      CSCR were randomly divided into three groups according to different wavelengths
      used. Visual acuity, fundus, fundus fluorescein angiography (FFA), light
      sensitivity, central visual field were performed before and after laser therapy.
      RESULT: Compared with red and green wavelength groups, in yellow group the visual
      acuity, light sensitivity were improved more significantly (P < 0.05), and the
      disease course was shortened, the effects in recurrence rate were similar in the
      three wavelength groups. CONCLUSION: In the three kinds of waves, yellow and red
      have similar and positive effects in the treatment of CSCR.

PMID- 11835849
TI  - [A study of vitrectomy for retinal redetachment with silicone oil retained].
AB  - OBJECTIVE: To evaluate the outcome of vitrectomy for retinal redetachment in eyes
      with silicone oil tamponade and investigate the indications and surgical
      techniques of this surgery. METHODS: A total of 17 eyes (17 cases), in which
      retinal redetachment developed after the management of silicone oil tamponade,
      underwent pars plana vitrectomy with silicone oil retained. Directed by
      endoilluminator, membrane peeling, membrane inside-cut, full thickness retinal
      incision, internal drainage, endolaser, removal of subretinal perfluorocarbon
      liquids and injection of additional silicone oil, etc. were performed to make
      retinal reattachment. RESULTS: 14 eyes achieved retinal reattachment in total 17
      eyes (82.4%). During operation, silicone oil migrated into anterior chamber in 1
      eye and into suprachoroidal space in 1 eye. There was 1 eye with vitreous
      hemorrhage and ocular hypertension postoperatively. Retinal reattachment was not
      achieved in 3 eyes. CONCLUSIONS: Vitrectomy with silicone oil retained is an
      effective management for retinal redetachment of eyes with silicone oil
      tamponade. The advantages of this method are economical and time-saving. But the
      surgeon should be well trained and competent with vitrectomy.

PMID- 11835850
TI  - [Optical coherence tomography of macular holes].
AB  - OBJECTIVE: To study the characteristics and clinical application value of the
      optical coherence tomography (OCT) of macular holes. METHOD: A total of 35
      patients with the clinical diagnosis of macular hole were examined with OCT
      between September and December 1998. OCT imaging was conducted through a dilated
      pupil, and the OCT images were analyzed and measured. RESULTS: Of the 35 patients
      examined with OCT, there were pseudohole and epimacular membrane in one eye,
      vitreofoveal traction in one eye, macular holes in 36 eyes, and 3 patients had
      macular hole in bilateral eyes. In 4 eyes, there were partial-thickness macular
      holes, and the defect of partial thickness of neural epithelium in the fovea
      without halo of retinal detachment was shown in the OCT image. In 32 eyes, there
      were full-thickness holes; the OCT displayed complete losing of the whole
      thickness of the neural epithelium in the fovea, sharp edge of the hole and the
      halo of retinal detachment around the hole. Sometimes nonreflective cavities
      could be seen within the retina, and the retinal thickness around the hole was
      increased. According to Gass stage classification of macular hole, there were 2
      eyes with impending hole, 3 eyes in stage 2, 15 eyes in stage 3 and 6 eyes in
      stage 4. 4 eyes underwent vitrectomy. The OCT imaging after the surgery
      demonstrated the closure of hole and the disappearance of halo surrounding the
      hole. Through quantitative measurement, the diameter of the hole was (565.88 +/-
      40.35) microm, the diameter of the halo was (1,338.76 +/- 147.57) microm, and the
      retinal thickness surrounding the hole was (391.87 +/- 18.97) microm. The sizes
      of the hole and the halo and the retinal thickness around the hole were
      correlated with the vision. CONCLUSION: OCT is a novel noninvasive, noncontact
      imaging technique. It is helpful in the diagnosis and differential diagnosis of
      the macular hole; the progress of the hole can be quantitatively estimated, and
      it is also helpful in selection of operation and assessment of operative
      therapeutic effects.

PMID- 11835851
TI  - [Magnetic resonance imaging in 40 cases of optic neuritis].
AB  - OBJECTIVE: To explore the clinical value of magnetic resonance imaging (MRI) in
      optic neuritis. METHODS: Forty patients with optic neuritis were examined with
      the spectral presaturation inversion recovery and fluid attenuated inversion
      recovery. RESULTS: The lesion was frequently seen in orbital portion (86.7%) and
      intracanalicular portion (29.3%), and primarily in the axial part (49.3%) and
      transverse section (38.7%) of the optic nerve. The longitudinal extent of lesion
      was from 2 to 35 mm (mean, 12.6 mm), the visual acuity of patients with optic
      neuritis was related to the site of the lesion, and negatively correlated with
      the longitudinal extent of lesion of logarithm curve. A poor visual acuity (<
      0.01) was significantly associated with lesion of greater extent > 10 mm and the
      transverse or axial lesion, but the good visual acuity (>or= 0.3), with the
      lesion of smaller extent < 10 mm and the axial or peripheral lesion. In addition,
      paramagnetic contrast-medium, Gd-DTPA, enhancement scanning was carried out in 11
      cases of optic neuritis, of them the visual acuity was increased in 10 cases
      after administration of corticosteroid, and in one case, visual improvement was
      not seen. CONCLUSION: MRI is a new and useful equipment which is helpful in the
      diagnosis and treatment of optic neuritis.

PMID- 11835852
TI  - [Computer-aided 3-D reconstruction and measurement of optic canal and
      intracanalicular structures].
AB  - OBJECTIVE: To reconstruct the human optic canal and its inner structures, and to
      provide knowledge of this region in detail for optic nerve decompression and
      further understanding on the pathologic mechanisms of indirect optic nerve
      injury. METHODS: 6 optic canals and its inner structures were reconstructed by
      using a computer-aided 3-dimensional (3-D) reconstruction system. Quantitative
      measurement for the canal wall thickness, bony canal transverse area, optic nerve
      transverse area, dual sheath transverse area, subarachnoid space transverse area,
      and subarachnoid space volume were done by means of the computer morphometric
      analysis system. The detailed spatial relations among intracanalicular structures
      were also carefully identified on the 3-D models. RESULTS: The thinnest portion
      of the canal was the middle part of the medial wall (0.45 +/- 0.35)mm, and the
      narrowest space was in the middle part of the optic canal [the transverse area
      was (18.21 +/- 2.50) mm(2)]. The volume of subarachnoid space which can be
      considered the compensatory space for distention incurred by the hemorrhage,
      optic nerve edema, or hematoma was (21.16 +/- 4.31) mm(3). At the cranial
      opening, the middle part and orbital opening, its transverse area was (4.45 +/-
      1.12) mm(2), (2.68 +/- 1.32) mm(2), (1.23 +/- 0.83) mm(2), respectively.
      CONCLUSIONS: In the middle part, the restraining of the bony canal on injured
      nerve may be the most powerful. Since the compensatory space was limited, even a
      tiny amount of blood or swelling of the nerve may cause optic compression.
      Because the compensatory space for distention gradually decreases from cranial
      end to orbital end, the middle part and the anterior part of the optic canal and
      dural sheath are critical in optic nerve decompression.

PMID- 11835853
TI  - [The characteristics of luminance of color visual evoked potential in macular
      diseases].
AB  - OBJECTIVE: To objectively evaluate the luminance channel damage of macular
      diseases by color pattern reversal visual evoked potential (CPR-VEP). METHODS:
      CPR-VEP was performed in 38 eyes with age-related macular degeneration (ARMD) dry
      type, 24 eyes with ARMD wet type, 20 eyes with Stargardt's disease and 54 normal
      eyes. Color pattern stimuli were obtained with color monitor controlled by
      computer program. Color pattern reversal rate was 2 Hz and its spatial frequency
      was 0.53 cycle/degree. The color graphic system could present white/black (W/B),
      red/black (R/B), green/black (G/B), blue/black (B/B), yellow/black (Y/B).
      RESULTS: In normal eyes, CPR-VEP P(1) latency was negatively correlated with
      luminance, whereas P(1) amplitude positively correlated with luminance; there
      were linear regressions between the mean luminance and P(1) latency and between
      the mean luminance and P(1) amplitude. Also in ARMD dry type, the CPR-VEP showed
      that the characteristics of the luminance channel were similar to that in the
      normal eyes. However, these phenomena did not exist in ARMD wet type and
      Stargardt's disease. CONCLUSION: In ARMD dry type, there is no damage of
      luminance channel, but in ARMD wet type and Stargardt's disease, there is severe
      damage of luminance channel and the patients can not discriminate luminance
      difference.

PMID- 11835854
TI  - [Treatment of age-related macular degeneration by surgical removal of subfoveal
      neovascular membrane with vitrectomy].
AB  - OBJECTIVE: To investigate the therapeutic effect of surgical removal of subfoveal
      neovascular membrane with vitrectomy in treatment of age-related macular
      degeneration. METHODS: 30 patients (30 eyes) with the macular degeneration were
      selected. The duration of the disease was limited less than 2 years and the size
      of the neovascular membrane was limited to <or= 3 disc diameters. The neovascular
      membrane was removed through the retinotomy superiotemporal to the macula after
      closed vitrectomy. The vitreous cavity was replaced by 30% SF(6) after gas/fluid
      exchange and the patients took prone position postoperatively. RESULTS: The
      visual acuity was improved in 17 (56.7%, the best one 20/60), unchanged in 8
      (26.7%) and decreased in 5 (16.7%) of the 30 eyes after operation. The post
      operative complications were as follows: retinal detachment in 1 eye, centripetal
      retinal pucker to the retinotomy in 3 eyes and recurrence of neovascular membrane
      in 3 eyes. Transmission electron microscopy showed that the specimens were mainly
      composed of neo-capillary vessels. CONCLUSIONS: Certain therapeutic effects can
      be seen after the operation. However, the improvement of visual acuity in most of
      the cases is not very significant.

PMID- 11835855
TI  - [A pathological study on indirect optic nerve injury in rabbit eyes].
AB  - OBJECTIVE: To study the pathological changes after indirect optic nerve injury.
      METHODS: Animal models (72 rabbits, 144 eyes) for intracanalicular optic nerve
      injury was developed by keeping the optic canal intact. The pathological changes
      of optic nerve were observed under light microscope and transmission electron
      microscope and the number of myelinated axons was enumerated by computer-aided
      image analyzer. The data were analyzed by using variance of SAS software.
      RESULTS: The model contributed much valuable information regarding nerve edema,
      loss of myelin, myelin regeneration and changes of axons. The edematous area in
      the optic nerve injury was reduced (P < 0.01) by treating with prednisone. The
      counted number of myelinated fibers showed more in the group treated by
      prednisone than that in the group without treatment. CONCLUSIONS: Significant
      changes of optic nerve after indirect injury are edema, demyelination and the
      change of axon amount. The effects of prednisone on reducing these pathological
      changes are demonstrated in this study.

PMID- 11835856
TI  - [Ultrastructural characteristics of epiretinal membranes].
AB  - OBJECTIVE: To investigate ultrastructural features and the correlation between
      the cell activation and extracellular matrix (ECM) expression of epiretinal
      membranes. METHODS: Immuno-electron-microscopy was done on the epiretinal
      membranes removed by vitrectomy from 16 patients with rhegmatogenous retinal
      detachment associated with proliferative vitreoretinopathy (PVR). The specimens
      were stained with antibodies to ECM proteins, including type I collagen, type III
      collagen and fibronectin (FN). RESULTS: A type of cells with a number of
      lamellipodia was found in membrane sections of 9 patients. The lamellipodia
      appeared to be either coiled or branched and were surrounded by abundant collagen
      fibers of type I and III. The cells with lamellipodia varied in their phenotypes
      and with or without pigment. There were dense gold particles of FN in contact
      regions of lamellipodia and collagen. CONCLUSIONS: Our observations support that
      the contraction of epiretinal membranes is the result of an interaction between
      cells and collagen, and the cells extending lamellipodia may initiate contractile
      events. FN is responsible for this contractile action.

PMID- 11835857
TI  - [A study on transplantation of rat photoreceptor cell layer].
AB  - OBJECTIVE: To study the relationship between photoreceptors and other layers of
      the retina in the aspects of anatomical structure, physiology, pathology, etc.
      METHODS: RCS rats were used as host animals, and the pure cone and rod layer of
      the donor retina was prepared from Wistar rat and was transplanted under the host
      retina where the cones and rods were degenerated. RESULTS: After 2 weeks of
      transplantation, the retinas of the host rats were reattached, and the
      transplanted cells were survival. The transplanted cells were in the subretinal
      space between the retinal pigment epithelium (RPE) and the inner unclear layer,
      and they had the staining characteristics similar to that of the normal control
      photoreceptors. CONCLUSION: In the animal model of photoreceptor cell layer
      transplantation, the transplanted cells possess normal anatomical location and
      are connected with RPE and inner nuclear layer. The results provide a new route
      to investigate the re-establishment of anatomical association with the optic
      nerve and the physiological activity of the nerve.

PMID- 11835858
TI  - [Ocular pharmacokinetics of pilocarpine micron emulsion in rabbits].
AB  - OBJECTIVE: To compare the pharmacokinetics of pilocarpine micron emulsion with
      generic pilocarpine solution in the aqueous humor. METHODS: 60 albino rabbits
      were used and were divided into 20 groups, each consisting of 3 animals. 10
      groups received 2% generic pilocarpine 50 microl as controls; 10 groups received
      50 microl of 2% pilocarpine micron emulsion in the conjunctival sac. The aqueous
      humor was withdrawn at 5, 10, 30, 40, 60, 90, 120, 180, 240 and 360 min. after
      instillation. The drug was extracted from aqueous humor with dichloromethane. The
      drug was analyzed by reversed phase high pressure liquid chromatography (HPLC).
      RESULTS: Pilocarpine micron emulsion therapy gave higher aqueous humor
      concentration of the drug than drops at all time periods tested except 5 min.
      time point (P = 0.0003 - 0.042). The area under curve of micron emulsion was 3
      times as much as that of drops. There was a two-fold increase in ocular
      bioavailability of pilocarpine due to the therapy with micron emulsion.
      Measurable amounts of drug following 2% micron emulsion were still observed at
      360 min. while drug levels at 180 min. following 2% drop therapy were nil.
      CONCLUSION: Our study results demonstrated significantly increase in ocular
      bioavailability of pilocarpine due to the therapy with micron emulsion. Our
      finding indicates that a novel topical preparation of pilocarpine incorporated in
      micron emulsion might serve as a long acting antiglaucoma agent, and less
      frequent applications are necessary with it than with conventional drops.

PMID- 11835859
TI  - [Investigation of the diplopia after intraocular lens implantation].
AB  - OBJECTIVE: To investigate the pathogenesis, mechanism and prognosis of diplopia
      after cataract extraction with intraocular lens implantation (IOL). METHODS:
      Besides routine ocular examinations, refraction, ocular position, ocular
      movement, fusional function and image of diplopia were examined on all the
      patients. Forced duction was examined on partial patients. RESULTS: Among 24
      cases with diplopia after IOL implantation, there were 19 cases of binocular
      diplopia and 5 cases of monocular diplopia. Of the binocular diplopia, there were
      17 cases of strabismic diplopia and 2 cases of diplopia due to central fusional
      impairment. Of the cases with monocular diplopia, there were 4 cases resulted
      from operative complication and one case with congenital iridocoloboma.
      CONCLUSIONS: The pathogenesis of strabismic diplopia resulted from dysfunction of
      ocular movement is unknown. Most of the patients can obtain binocular vision by
      early active treatment. Monocular diplopia is partly resulted from operative
      complication.

PMID- 11835860
TI  - [In vitro adherence of bacteria to intraocular lenses of different materials].
AB  - OBJECTIVE: To compare the in vitro adherence of different bacteria onto the
      surface of various intraocular lenses (IOLs). METHOD: Electron microscopic and
      bacterial culture quantitative methods were used to study the adherence of
      Staphylococcus (S) epidermidis, Staphylococcus aureus and Pseudomonas (P)
      aeruginosa onto the surface of PMMA and other three foldable IOL materials (HEMA,
      ACRY, SI). RESULTS: S. Epidermidis: HEMA < ACRY < SI < PMMA; S. aureus: HEMA was
      the least and PMMA was the most, no significant difference between ACRY and SI
      IOLs; P. aeruginosa: HEMA was the least while no significant difference among
      PMMA, SI and ACRY IOLs (P > 0.05). CONCLUSION: The foldable IOLs have the potent
      ability to reduce the infectious endophthalmitis after surgery of extraction of
      cataract with IOL implantation.

PMID- 11835861
TI  - [LASIK for high and moderate hyperopia].
AB  - OBJECTIVE: To evaluate safety and efficacy of excimer laser in situ
      keratomileusis (LASIK) for high and moderate hyperopia. METHODS: LASIK was
      performed on 17 eyes of 9 patients using the SCHWIND KERATOM-F excimer laser. The
      range of preoperative spherical equivalent was + 5.50 to + 9.00 D, and its mean
      value, (+ 7.18 +/- 1.00) D. All the cases were followed up for 12 months or
      longer. RESULTS: There was no serious complication during the operation. No eye
      lost more than 1 line of the best corrected visual acuity after surgery. At 12
      months, the mean postoperative spherical equivalent was (+ 1.77 +/- 1.56) D.
      52.9% of eyes reached 0 to + 1.00 diopter. 88.2% of eyes achieved an uncorrected
      far vision of >or= 0.5. 100.0% and 76.5% eyes got uncorrected near visual
      acuities of >or= 0.5 and >or= 1.0 respectively. CONCLUSION: It is demonstrated
      the LASIK is a safe and effective technique for the treatment of high and
      moderate hyperopia. Further algorithm calibration must be made to avoid
      undercorrection.

PMID- 11835862
TI  - [Use of visual aids for vision of disabled children].
AB  - OBJECTIVE: To discuss the effect of using distance and near optical low vision
      devices for children in low vision clinic. METHOD: 139 subjects from age 6 to 14
      years were provided with 2.5 X telescopes and + 8.00D to + 40.00D glasses for
      improving far and near sight respectively. RESULT: 22.3% subjects' distance
      visual acuity was >or= 0.5 and 53.2% subjects' near visual acuity was >or= 0.5
      after using distance and near low vision aids. CONCLUSIONS: Low vision aid is
      essential and effective in low vision clinic. It not only improves the visual
      acuity of visual disabled children, but also helps the development of special
      education through visual rehabilitation.

PMID- 11835863
TI  - [Effect of bFGF, IGF-I and their synergy on the mitogenesis of bovine lens
      epithelial cells].
AB  - OBJECTIVE: To assess the effect of basic fibroblast growth factor (bFGF), insulin
      like growth factor-I (IGF-I) and their synergy on the mitosis of bovine lens
      epithelial cells (BLECs). METHODS: BLECs were cultured in vitro. The fourth
      passage cells were inoculated into 24 well tissue culture plates, treated with
      different concentrations of bFGF, IGF-I, and bFGF + 20 microg/L IGF-I for 20
      hours, (3)H-thymidine was added for 16 hours, then the radioactivity was
      determined by liquid scintillation counting. RESULTS: Either bFGF (1 - 100
      microg/L) or IGF-I (20 - 100 microg/L) increases mitosis of BLEC significantly,
      and 20 microg/L IGF-I may increase bFGF induced mitogenesis. CONCLUSION: Growth
      factor and their synergic effect may play an important role in lens epithelial
      cell proliferation.

PMID- 11835864
TI  - [The prevalence of cataract in Doumen County, Guangdong Province].
AB  - OBJECTIVE: To investigate the prevalence of cataract, cataract blindness and the
      cataract burden in population aged >or= 50 years in Doumen County. METHOD: 5,759
      individuals aged >or= 50 were identified from sampling units. The definition of
      cataract was the vision < 0.7 caused by lens opacity in either eye, among them
      the person whose vision in both eyes was < 0.1 was cataract burden and whose
      vision in both eyes was < 0.05 was cataract blindness. RESULT: The response rate
      was 92.76%. The prevalence of cataract, cataract blindness and cataract burden
      was 20.93%, 1.67% and 3.86%, respectively. CONCLUSION: The huge community
      necessary for cataract surgery still remains as a great challenge in China.

PMID- 11835865
TI  - [Echoendoscopy: past, present and future].

PMID- 11835866
TI  - [Gastrointestinal echoendoscopy: technical aspects and tools].

PMID- 11835867
TI  - [Echoendoscopy in the diagnosis and extension of digestive neoplasias].

PMID- 11835869
TI  - [Role of echoendoscopy in the study of gastric diseases with fold thickening and
      in gastric lymphomas].

PMID- 11835868
TI  - [Utility of echoendoscopy in the evaluation of submucosal tumors and extrinsic
      compressions of the digestive tract].

PMID- 11835870
TI  - [Echoendoscopy of the pancreas].

PMID- 11835871
TI  - [Echoendoscopy and biliary disease].

PMID- 11835873
TI  - [Diagnostic and therapeutic interventional echoendoscopy].

PMID- 11835872
TI  - [Echoendoscopy in portal hypertension and benign digestive tract disease].

PMID- 11835874
TI  - [Cytological diagnosis in digestive system echoendoscopy].

PMID- 11835875
TI  - [Role of echoendoscopy in diagnostic and therapeutic strategies in
      gastrointestinal oncology].

PMID- 11835876
TI  - [Hormonal oral contraceptives, coagulation and thrombosis].

PMID- 11835877
TI  - [Hospital discharge reports may be an inadequate source of information to
      evaluate care quality].
AB  - OBJECTIVES: To examine whether there is adequate available information in
      hospital discharge records (HDR) to retrospectively evaluate the adequacy of
      medical care to patients suffering from ischemic heart disease (IHD) and to
      relate care quality to physicians' decisions. MATERIAL AND METHODS: Cross
      sectional study in which a total of 690 HDRs of patients admitted to three
      university teaching hospitals in Seville, Spain, on account of ischemic heart
      disease. The fulfillment of 15 parameters representing an adaptation to the CMBD
      regulation to IHD. The criterion of adequate information was set at 80% of data.
      RESULTS: Only 2.8% of HDRs contains adequate information. According to the
      analysed data, relevant fulfillment variability was observed. There were
      significant differences in fulfillment depending upon hospital and type of
      patient, with more information among younger patients and comorbidity.
      CONCLUSIONS: HDRs contain inadequate information to evaluate medical care.

PMID- 11835878
TI  - [The transition from acute to chronic ischemic heart disease in Spain, 1980
      1994].
AB  - BACKGROUND AND OBJECTIVES: The remarkable increase in hospital admissions from
      heart failure in Spain in the last few years may result paradoxical because it
      coincides with a decrease in ischemic heart disease mortality, the leading cause
      of heart failure. A plausible explanation is the increase in ischemic heart
      disease survival, derived from the recent therapeutic advances, which will
      translate into an increase in the chronic forms of disease. Thus, an analysis was
      made of mortality and hospital admission trends due to acute and chronic ischemic
      heart diseases in the 1980-1994 period in Spain. METHODS: Population-based study
      of temporal trends with data of primary diagnosis of acute (CIE-9: 410-411) and
      chronic (CIE-9: 412-414) ischemic heart disease obtained from the National Vital
      Statistics and the National Survey of Hospital Morbidity. RESULTS: The number of
      deaths due to acute ischemic heart disease has increased by 8.3%, from 18,559 in
      1980 to 20,101 in 1994. Deaths due to chronic ischemic heart disease increased by
      49.3%, from 4,703 in 1980 to 7,020 in 1994. As a result, chronic forms accounted
      for 20.2% of all deaths attributable to ischemic heart disease in 1980 and 25.8%
      in 1994. The age-adjusted acute ischemic heart disease mortality rates decreased
      by 20.1%, whereas those due to chronic increased by 14.6%. The number and rate of
      age-adjusted hospital admissions increased remarkably for both acute and chronic
      ischemic heart disease. Nevertheless, the increase observed with chronic form was
      higher, from 39.4% of all hospital admissions due to ischemic heart disease in
      1980 to 58.4% in 1994. This classification of ischemic heart disease was more
      notorious among males and younger patients. CONCLUSION: Currently, we are
      witnessing a transition from acute to chronic ischemic heart disease. That partly
      explains the increase in hospital care for heart diseases, particularly ischemic
      heart disease and heart failure.

PMID- 11835880
TI  - [Evolution of antithrombin activity and plasma fibrinogen levels and of
      hematologic values among women in child-bearing age on treatment with the new
      hormonal oral contraceptives].
AB  - OBJECTIVE: To study the evolution of antithrombin (AT) and plasma fibrinogen
      levels and of hematologic values among women in child-bearing age on treatment
      with the new hormonal oral contraceptives (HOC): in microdose, ultramicrodose and
      Diane-35. METHOD: Retrospective review of 100 randomized cases out of a total
      registry of 1,245 clinical records. RESULTS: The mean age in our series was 23.4
      years (range: 18-39 years). The mean study time was 3.3 years (range: 1-5 years).
      During the study period, there was not a single woman with an AT lower than 70%.
      There were no significant changes at the end of the study period regarding AT,
      plasma fibrinogen, hematocrit, hemoglobin, prothrombin activity and activated
      partial thromboplastin time. A significant decrease was observed for platelet
      count (246,113 5,842 vs. 215,636 4,383 platelets/mm3; p = 0.003). There was not a
      single case of thrombocytopenia registered. No relevant differences were observed
      between the treatment groups with microdosaged, ultramicrodosaged and Diane-35.
      CONCLUSIONS: At mid-term (3.3 years), the new HOC (in microdose, ultramicrodose
      and Diane-35), do not cause significant changes in AT, plasma fibrinogen,
      hematocrit, hemoglobin, prothrombin activity and activated partial thromboplastin
      time. In our series, a moderate but significant decrease in the platelet count
      was observed but there were no cases of thrombocytopenia. The effect of the
      different new HOC on the studied parameters was similar.

PMID- 11835879
TI  - [Etiology of hemoptysis: Prospective analysis of 752 cases].
AB  - OBJECTIVES: To know the etiology of hemoptysis and its distribution in our area
      compared with other current and historic series. METHODS: Prospective,
      descriptive study of 752 cases of hemoptysis. The etiology of these cases was
      determined by evaluating the clinical record, chest X-ray, functional respiratory
      tests and sputum smear for acid-fast bacilli, together with other examinations
      such as bronchoscopy and computerized tomography (CT) according to previously
      established criteria. RESULTS: The mean age of patients was 60 years (SD: 15
      years), 79% were males and 75% smokers. Diagnoses included neoplasms (28%),
      chronic bronchitis (19.8%), bronchiectasis (14.5%), pneumonia or lung abscess
      (11.5%), idiopathic forms (8%), and miscellaneous causes with lower percentages
      such as tuberculosis (1.7%) and its sequelae (4%), cardiac diseases (1.5%) and
      pulmonary embolism (2.3%). Bronchoscopy was performed in 694 (92.2%) and detected
      the bleeding site or provided a specific diagnosis in 39% (81% if only neoplasms
      are considered) and non-specific but abnormal in 57%. The amount of bleeding was
      small in most cases and kept no relationship with causes. CONCLUSIONS: Neoplasms,
      chronic bronchitis and bronchiectasis are the most common causes of hemoptisis in
      our area. Bronchiectasis and tuberculosis have decreased compared with previous
      series used as reference. In contrast, there has been an increase in the number
      of neoplasms and chronic bronchitis and a plateau in those attributed to cardiac
      diseases, pneumonia or lung abscess and cryptogenetic forms. To obtain the
      origin, bronchoscopy complemented by CT remains essential.

PMID- 11835881
TI  - [Clinical suspicion and diagnosis of aortitis].

PMID- 11835882
TI  - [Therapeutic management of acute ischemic heart disease without ST increase].

PMID- 11835883
TI  - [Subclinical hyperthyroidism].

PMID- 11835884
TI  - [Clinical and therapeutic significance of hepatitis B virus heterogeneity].

PMID- 11835885
TI  - [False negative and false positive results of tumor markers: their limitation in
      clinical practice. Clinical applications of CA-125].

PMID- 11835886
TI  - [Physicians and the legal system (V): the professional secret].

PMID- 11835887
TI  - [Sudden dysphagia in a 60-year old male. Achalasia].

PMID- 11835888
TI  - [Diarrhea in a 49-year old female with overlap syndrome. Celiac disease].

PMID- 11835889
TI  - [Pregnant woman with left hemiparesis and yellowish papules. Pseudoxanthoma
      elasticum].

PMID- 11835890
TI  - [Cystic lesion in chest wall in a patient with epidermoid carcinoma of the base
      of the tongue].

PMID- 11835891
TI  - [Inappropiate use of presurgical chest X-ray in a public hospital network].

PMID- 11835892
TI  - [Rhabdomyolysis associated with combined treatment of cerivastatin and
      gemfibrozil].

PMID- 11835893
TI  - [Influenza vaccine in patients infected with the human immunodeficiency virus,
      should it be administered to all patients?].

PMID- 11835895
TI  - The effects of drug-sensitive and drug-resistant Trypanosoma congolense
      infections on the pharmacokinetics of homidium in Boran cattle.
AB  - Two groups of five Boran (Bos indicus) cattle were infected with one of two
      populations of Trypanosoma congolense; one drug-sensitive (IL1180), and one drug
      resistant (IL3330). The animals were then treated intramuscularly with homidium
      bromide at a dose rate of 1.0 mg kg(-1) bodyweight 7 days after trypanosomes were
      detected in the peripheral blood of all the five animals in each group. Following
      treatment of cattle infected with drug-sensitive trypanosomes, parasites could no
      longer be detected in the bloodstream of four out of five cattle after 24 h, and
      after 48 h for the fifth animal. The animals remained aparasitaemic up to the end
      of the observation period of 90 days and serum drug concentrations determined by
      enzyme-linked immunosorbent assay (ELISA) remained above the detection limit of
      0.1 ng ml(-1) for the entire period. Following treatment of cattle infected with
      drug-resistant trypanosomes, parasites did not disappear from the bloodstream in
      any of the five animals. The rate of drug elimination was greater in cattle
      infected with drug-resistant trypanosomes and the drug was no longer detectable
      approximately 3 weeks after treatment. Non-compartmental pharmacokinetic analysis
      showed that the values for t(12)beta of 75.5 +/- 16.9 h, the area under the curve
      (AUC(0-infinity)) of 1.33 +/- 0.156 microg h ml(-1) and the MRT(0-infinity) of
      32.8 +/- 4.45 h obtained in cattle infected with the drug-resistant trypanosome
      population were significantly lower than the values of 424 +/- 146 h for
      t(12)beta, 1.67 +/- 0.233 microg h ml(-1) for AUC(0-infinity) and 297 +/- 159 h
      for MRT(0-infinity) obtained in cattle infected with the drug-sensitive
      population. The persistence of drug-resistant infections in cattle following
      homidium treatment was associated with more rapid drug elimination than in those
      in which infections with drug-sensitive parasites were cleared by the drug.

PMID- 11835896
TI  - Usefulness of sampling with cotton swab for PCR-diagnosis of cutaneous
      leishmaniasis in the New World.
AB  - In this study, we tested the polymerase chain reaction (PCR)-method to diagnose
      cutaneous leishmaniasis (CL) by taking exudate materials from lesions with cotton
      swabs, using our previously tested (PCR) panel comprised of Leishmania (Viannia)
      panamensis, L. (V.) braziliensis, L. (V.) guyanensis, L. (Leishmania) mexicana
      and L. (L.) amazonensis. The objectives of the present study were to improve the
      sampling method convenient for the patients and to test the usefulness of samples
      taken with cotton swabs. Sixteen patients were clinically diagnosed to have CL
      including one case of diffuse cutaneous leishmaniasis (DCL) in Ecuador and the
      causative Leishmania parasites were identified by PCR. All the 12 samples from CL
      patients of La Mana, positive for Leishmania DNA, were identified as L. (V.)
      panamensis, while two from CL of Huigra and one from DCL of San Ignacio were L.
      (L.) mexicana. In the field condition, taking biopsy material is not only painful
      but sometimes causes iatrogenic bacterial infections. Considering the sensitivity
      of the test, and convenient sampling procedure, it may be suggested that
      collection of exudates using cotton swabs may be a better alternative to biopsy
      sample for PCR-diagnosis of CL.

PMID- 11835897
TI  - Experimental Trypanosoma evansi infection in South American coati (Nasua nasua):
      hematological, biochemical and histopathological changes.
AB  - The course of an experimental Trypanosoma evansi infection in coatis (Nasua
      nasua, carnivora, Procyonidae) was followed for 262 days. Hematological analysis
      of the infected coatis revealed a marked decline in hemoglobin, packed-cell
      volume, and total erythrocyte count. An intense anemia followed the first wave of
      parasitemia and persisted until the end of the experimental period. Biochemical
      analysis showed increased serum levels of alanine aminotransferase and aspartate
      aminotransferase and decreased albumin. The main histopathological features
      consisted of myocarditis with the presence of degenerate cardiac fibers and
      meningoencephalitis. This study has shown that coatis infected with T. evansi
      develop a chronic disease.

PMID- 11835898
TI  - Laboratory and field comparisons of pyriproxyfen, polystyrene beads and other
      larvicidal methods against malaria vectors in Sri Lanka.
AB  - Hand-dug gem pits are important breeding sites for larvae of malaria vectors in
      Sri Lanka. Therefore, studies were carried out to help to select an effective,
      economic and convenient method that could be used to control malaria vector
      mosquito breeding in gem pits in a mining area. The effectiveness of four types
      of floating layers of polystyrene was compared in the laboratory and it was found
      that 2 mm expanded beads were the most effective for suffocating Anopheles larvae
      and pupae. The insect growth regulator, pyriproxyfen at dosages of 0.01 and 0.1
      mg/l were tested in the laboratory and complete inhibition of emergence was found
      at both concentrations. A small-scale field trial was carried out for over a year
      to assess the efficacy of two concentrations of pyriproxyfen, 2 mm diameter
      expanded polystyrene beads, temephos, used engine oil and filling pits with soil.
      Pyriproxyfen only required re-application twice a year, whereas temephos or oil
      require 12 applications per year. Due to re-excavation by gem miners, polystyrene
      beads and filling of pits were not as permanent solutions as was expected.
      Calculations based on all available data showed that two annual treatments with
      pyriproxyfen at 0.01 mg/l would be the most cost-effective method with oil only
      slightly more expensive. However, the reduced required frequency for visiting
      every pit made the pyriproxyfen method the one of choice. The same low
      concentration of pyriproxyfen also effectively inhibited emergence of adults from
      river-bed pools.

PMID- 11835899
TI  - Characterization of Trypanosoma brucei s.l. subspecies by isoenzymes in domestic
      pigs from the Fontem sleeping sickness focus of Cameroon.
AB  - Though it has been established that domestic animals (especially the pig) are
      potential reservoir hosts for Trypanosoma brucei gambiense in West Africa, there
      is little data to this effect concerning Central Africa. Instead, some previous
      authors report the absence of Trypanozoon type trypanosomes in domestic animals
      in Cameroon. Thirty-two domestic pigs were sampled by KIVI (kit for in vitro
      isolation) of trypanosomes in the northern region (Bechati) of the Fontem
      sleeping sickness focus of Cameroon. Twenty-one of these were found positive,
      from 15 of which 17 isolates were successfully obtained. Isoenzyme
      characterization revealed that isolates from 4 of the 15 pigs belonged to
      zymodemes associated with T. brucei gambiense group 1. The prevalence of this
      disease in the local human population is, however, very low. It is evident from
      this study that the domestic pig may be a potential reservoir host for T. brucei
      gambiense in the Fontem focus. There is, however, need for an extensive study on
      domestic animals in Cameroon and other neighbouring countries for a better
      comprehension of the epidemiology of sleeping sickness within the Central African
      region.

PMID- 11835900
TI  - Presence of hemagglutination inhibition and neutralization antibodies to Japanese
      encephalitis virus in wild pigs on an offshore island in Singapore.
AB  - A study was conducted to determine the presence of hemagglutination inhibition
      (HI) and neutralization antibodies against Japanese encephalitis virus (JEV) in
      wild pigs on an offshore island in Singapore. Blood samples were collected from
      28 wild pigs on the island. All the sera tested with HI assay and plaque
      reduction neutralization tests were found to be positive for antibodies against
      JEV. Our results indicate that the wild pigs have been infected with JEV on the
      offshore island and there is JEV transmission.

PMID- 11835901
TI  - Charles Wilberforce Daniels, FRCP (1862-1927): underrated pioneer of tropical
      medicine.
AB  - Charles Wilberforce Daniels was a major pioneer in the early days of the newly
      formed medical specialism--tropical medicine. At the London School of Tropical
      Medicine (LSTM) of which he was a leading stalwart, he took an active part in
      research, teaching and administration. But like others in the new discipline he
      spent a great deal of time at various tropical locations: Fiji, British Guiana-
      where he made important observations on various forms of filariasis-- east
      Africa, and Malaya. However, his most important research contribution was
      arguably confirmation of Ronald Ross' 1898 discovery of the complete life-cycle
      of avian malaria, in Calcutta.

PMID- 11835903
TI  - The role of the renin-angiotensin system in the development of cardiovascular
      disease.
AB  - A direct, continuous, and independent relation between blood pressure and the
      incidence of various cardiovascular events, such as stroke and myocardial
      infarction, is now well accepted. The increase in risk can be attributed to
      structural and functional changes in target organs. Central to many of these
      pathophysiologic processes is the renin-angiotensin system (RAS), specifically,
      angiotensin II. Binding of angiotensin II to angiotensin II type-1 (AT(1))
      receptors produces acute vasoconstriction, leading to an increase in blood
      pressure. AT(1) receptor activation also contributes independently to chronic
      disease pathology by promoting vascular growth and proliferation, and endothelial
      dysfunction. These negative consequences of angiotensin II are partly
      counteracted by angiotensin II type-2 (AT(2)) receptor stimulation, which has
      favorable effects on tissue growth and repair processes. Thus, the use of
      selective AT(1) receptor antagonists in the treatment of hypertension has a 2
      fold rationale: (1) selective AT(1) receptor blockade targets the final common
      pathway for all major detrimental cardiovascular actions of angiotensin II, and
      (2) circulating angiotensin II levels (which increase during AT(1) receptor
      antagonist treatment) will be free to act only at unopposed AT(2) receptors,
      potentially providing additional end-organ protection. Angiotensin-converting
      enzyme (ACE) inhibitors interrupt the RAS by preventing the conversion of
      angiotensin I to angiotensin II. They also increase plasma levels of bradykinin,
      which possesses vasodilatory and tissue-protective properties. The combination of
      an AT(1) receptor antagonist with an ACE inhibitor represents an appealing
      therapeutic strategy, because it should produce more complete blockade of the
      RAS, while preserving the beneficial effects mediated by AT(2) receptor
      stimulation and increased bradykinin levels.

PMID- 11835905
TI  - Angiotensin II and trials of cardiovascular outcomes.
AB  - Proven cardiovascular benefit from angiotensin-converting enzyme (ACE) inhibition
      is a cornerstone of evidence-based medicine. The first study to show dramatic
      benefits from ACE inhibition was the Cooperative North Scandinavian Enalapril
      Survival Study (CONSENSUS-I), in which a 31% decrease in the rate of death was
      observed in patients with severe heart failure at the end of 1 year of enalapril
      treatment (p = 0.001). This result led to large long-term studies-including
      Survival and Ventricular Enlargement (SAVE), Acute Infarction Ramipril Efficacy
      (AIRE), Trandolapril Cardiac Evaluation (TRACE), and Study of Left Ventricular
      Dysfunction (SOLVD)-which verified that ACE inhibition decreases heart failure,
      myocardial infarction (MI), and mortality, and that striking benefit could be
      observed within 30 days. Short-term studies of patients in the acute phase of a
      heart attack verified that ACE inhibition provided rapid benefits. A meta
      analysis of short-term (up to 8 weeks) studies of ACE inhibition (including
      CONSENSUS-II, Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto
      Miocardico [GISSI]-3, International Study of Infarct Survival [ISIS]-4, and the
      Chinese Captopril Study [CCS]-1) demonstrated that post-MI risk was reduced by
      10% within the first day of treatment. The immediacy of the benefit suggested
      that ACE inhibition not only improved cardiovascular function in failing hearts
      but also affected important mechanisms in patients without overt heart failure.
      Effects on more general mechanisms of heart disease suggested that patients with
      problems other than hypertension or heart failure might benefit from ACE
      inhibitors. The Heart Outcomes Prevention Evaluation (HOPE) study investigated
      the hypothesis that ACE inhibition would confer benefits to patients who were at
      high risk for cardiovascular events, but who were without left ventricular
      dysfunction or heart failure. Long-term reductions in MI, stroke, cardiac arrest,
      and heart failure, as well as improvements in mortality, were observed in this
      population after treatment with ACE inhibitors. Substudies of the HOPE study
      revealed that ACE inhibition reduced progression of atherosclerosis and improved
      myocardial remodeling. Taken together, these studies provide evidence that
      supports treatment of a broad population of patients at risk for cardiovascular
      events with ACE inhibitors. The next step is to combine ACE inhibition with other
      treatments to maximize patient benefit. The Ongoing Telmisartan Alone and in
      combination with Ramipril Global Endpoint Trial (ONTARGET) will compare the
      efficacy of an ACE inhibitor (ramipril) with an angiotensin receptor blocker
      (telmisartan), and determine whether these treatments in combination will further
      reduce morbidity and mortality from cardiovascular disease.

PMID- 11835907
TI  - From the HOPE to the ONTARGET and the TRANSCEND studies: challenges in improving
      prognosis.
AB  - The Heart Outcomes Prevention Evaluation (HOPE) study conclusively demonstrated
      that ramipril, an angiotensin-converting enzyme (ACE) inhibitor, reduces the risk
      of cardiovascular death, myocardial infarction (MI), and death in patients at
      risk for cardiovascular events but without heart failure. The Study to Evaluate
      Carotid Ultrasound Changes in Patients Treated with Ramipril and Vitamin E
      (SECURE) substudy demonstrated that ramipril also reduced atherosclerosis. These
      results suggest that the renin-angiotensin system (RAS) has a more important role
      in the development and progression of atherosclerosis than previously believed,
      and they indicate the need for further clinical studies to define the range of
      benefits available from modifying the RAS. Achieving maximum benefit may require
      treatment with both an ACE inhibitor and an angiotensin II type-1 receptor
      blocker (ARB). The Randomized Evaluation of Strategies for Left Ventricular
      Dysfunction (RESOLVD) study indicated that combining an ACE inhibitor with an ARB
      decreased blood pressure and improved the ejection fraction more than treatment
      with either drug alone in patients with congestive heart failure. The Valsartan
      in Heart Failure Trial (Val-HeFT) showed that the combination of an ACE inhibitor
      and an ARB reduced hospitalization for heart failure in patients with congestive
      heart failure by 27.5%, although no decrease in all-cause mortality was observed.
      The Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint
      Trial (ONTARGET) is a large, long-term study (23,400 patients, 5.5 years). It
      will compare the benefits of ACE inhibitor treatment, ARB treatment, and
      treatment with an ACE inhibitor and ARB together, in a study population with
      established coronary artery disease, stroke, peripheral vascular disease, or
      diabetes with end-organ damage. Patients with congestive heart failure will be
      excluded. In a parallel study, patients unable to tolerate an ACE inhibitor will
      be randomized to receive telmisartan or placebo (the Telmisartan Randomized
      Assessment Study in ACE-I Intolerant Patients with Cardiovascular Disease
      [TRANSCEND]). The primary endpoint for both trials is a composite of
      cardiovascular death, MI, stroke, and hospitalization for heart failure.
      Secondary endpoints will investigate reductions in the development of diabetes
      mellitus, nephropathy, dementia, and atrial fibrillation. These 2 trials are
      expected to provide new insights into the optimal treatment of patients at high
      risk of complications from atherosclerosis.

PMID- 11835909
TI  - The 24-hour blood pressure pattern: does it have implications for morbidity and
      mortality?
AB  - The onset of adverse cardiovascular events demonstrates a circadian pattern that
      reaches a peak in the morning shortly after awakening and arising. A parallel, 24
      hour cyclical pattern has also been observed in the activities of various
      physiologic measurements, including blood pressure, heart rate, sympathetic
      nervous system activity, and platelet adhesiveness. Although a direct link has
      not yet been established, it can be postulated that the early morning surge in
      blood pressure may be a factor in precipitating acute cardiovascular episodes.
      Similar to the early morning blood pressure surge, blood pressure variability
      throughout the day appears to be a further independent risk factor for
      hypertensive target organ damage. Thus, it is reasonable to select an
      antihypertensive agent that offers smooth and well-sustained blood pressure
      control for the full 24-hour dosing interval, including the vulnerable early
      morning period. The results of clinical trials using ambulatory blood pressure
      monitoring have shown that telmisartan, an angiotensin II receptor antagonist,
      possesses such properties. Whether or not these attributes of telmisartan might
      translate into improvements in cardiovascular morbidity and mortality will be
      explored in the Ongoing Telmisartan Alone and in Combination with Ramipril Global
      Endpoint Trial (ONTARGET). This study will compare the effects of telmisartan 80
      mg monotherapy, ramipril 10-mg monotherapy, or a combination of telmisartan 80 mg
      plus ramipril 10 mg, on cardiovascular endpoints in patients at high risk of
      cardiovascular events, several of whom are likely to be hypertensive at baseline.
      Inclusion of the telmisartan plus ramipril treatment arm will allow investigation
      of the potential advantages presented by combining an angiotensin-converting
      enzyme inhibitor with an angiotensin II receptor antagonist.

PMID- 11835911
TI  - Effect of local delivery of L-arginine on in-stent restenosis in humans.
AB  - To determine whether intramural administration of L-arginine reduces intimal
      thickening after optimal Palmaz-Schatz stent deployment in humans, 50 patients
      with native coronary artery disease who received a single Palmaz-Schatz stent
      were enrolled in this pilot study. Patients were randomized into 2 treatment
      groups: an L-arginine group (n = 25) and a saline group (n = 25). After stent
      deployment, L-arginine (600 mg/6 ml) or saline (6 ml) was locally delivered via
      the Dispatch catheter (Scimed) over 15 minutes. Serial angiography and
      intravascular ultrasound examinations (motorized pull-back at 0.5 mm/s) were
      performed before and after the procedure, and at 6-month follow-up. Measurements
      of stent area, lumen area, and neointimal area were computed within the stents at
      1-mm intervals, by technicians who were blinded to the treatment assignment.
      Using Simpson's rule, stent, plaque, and lumen volumes, neointimal volume within
      the stent, and percent neointimal volume were measured before and after the
      procedure, and at 6-month follow-up. The 6-month volume data in quantitative
      coronary ultrasound showed that neointimal volume in the L-arginine group was
      significantly less than in the saline group (25 vs 39 mm(3); p = 0.049).
      Similarly, percent neointimal volume was significantly less in the L-arginine
      group at 6-month follow-up (17 +/- 13% vs 27 +/- 21%; p = 0.048). Thus, these
      results showed that local delivery of L-arginine reduces in-stent neointimal
      hyperplasia in humans, indicating that this approach may be a novel strategy to
      prevent in-stent restenosis.

PMID- 11835912
TI  - Relation between residual plaque burden after stenting and six-month angiographic
      restenosis.
AB  - The degree of residual plaque burden outside of a stent might be correlated with
      the degree of intimal hyperplasia. However, the relation between residual plaque
      burden and angiographic restenosis are still unknown in a large number of
      patients. Therefore, we evaluated the effect of residual plaque burden after
      stenting on 6-month angiographic restenosis. Intravascular ultrasound (IVUS)
      guided coronary stenting was successfully performed in 723 patients with 785
      native coronary lesions. Six-month follow-up angiograms and evaluation of
      residual plaque burden by IVUS were available in 566 patients (78.3%) with 622
      lesions (79.2%). Results were evaluated using conventional methods. The overall
      angiographic restenosis rate was 23.0% (143 of 622 lesions). There was no
      significant difference in residual plaque burden between the lesions with and
      without restenosis (52% vs 51%, respectively, p = 0.148). The angiographic
      restenosis rate was 20.8% (11 of 53 lesions), 21.6% (51 of 236 lesions), 22.0%
      (55 of 250 lesions), and 31.3% (26 of 83 lesions) in the lesions with residual
      plaque burden < 40%, between 40% and 50%, between 50% and 60%, and > 60%,
      respectively (p = 0.284). Using multivariate logistic regression analysis, the
      only independent predictor of angiographic restenosis was the IVUS stent area
      (odds ratio 0.807, 95% confidence intervals 0.69 to 0.95, p = 0.011).
      Furthermore, even in the lesions with residual plaque burden > 60%, the
      restenosis rate was 37.3% (23 of 61 lesions) versus 13.6% (3 of 22 lesions ) in
      IVUS stent areas of < 7 and > or =7 mm(2), respectively (p = 0.031). In
      conclusion, residual plaque burden outside the stent might not predict
      angiographic restenosis. IVUS stent area was the only independent predictor of
      angiographic restenosis.

PMID- 11835913
TI  - Prognostic value of interleukin-1 receptor antagonist in patients undergoing
      percutaneous coronary intervention.
AB  - Elevated plasma levels of inflammatory markers, such as C-reactive protein (CRP),
      have been associated with adverse outcome in selected patients with coronary
      artery disease (CAD) treated with coronary angioplasty or stenting. The aim of
      this study was to evaluate the predictive value of preprocedural interleukin-1
      receptor antagonist (IL-1Ra) plasma levels for long-term major adverse cardiac
      events (MACE) in a series of unselected patients with symptomatic CAD treated
      with percutaneous coronary intervention (PCI). Seventy-three consecutive patients
      (62 men, aged 62 +/- 9 years) undergoing PCI were enrolled in a prospective
      follow-up study. IL-1Ra and CRP plasma levels were measured before the procedure;
      36 patients (49%) had unstable angina pectoris on admission, 37 (51%) had chronic
      stable angina pectoris, and 30 (41%) had multivessel CAD, 15 of whom underwent
      multivessel PCI. Success was achieved in all 73 patients, with coronary stenting
      performed in 63 (86%). Follow-up clinical assessment included occurrence of MACE
      at 3, 6, 12, and 18 months. Logistic regression analysis, performed to determine
      independent predictors of MACE, identified IL-1Ra levels in the upper quartile as
      the only independent predictive factor of MACE at 18 months (19% in the fourth
      quartile vs 0% in the first quartile; p = 0.032). Patients with high
      preprocedural CRP levels (fourth quartile) had a nonsignificant increased risk of
      MACE (p = 0.09). Thus, preprocedural IL-1Ra plasma levels appear to be a valuable
      independent predictive factor of MACE in unselected patients undergoing PCI.

PMID- 11835914
TI  - Usefulness of fractional flow reserve for risk stratification of patients with
      multivessel coronary artery disease and an intermediate stenosis.
AB  - Intracoronary-derived, pressure-based fractional flow reserve (FFR) is important
      for clinical decision-making in patients with 1-vessel coronary artery disease
      (CAD). In the present study, we investigated the prognostic value of FFR in
      patients with intermediate stenoses and multivessel CAD. Therefore, we analyzed
      107 patients with stable angina pectoris who underwent myocardial perfusion
      scintigraphy and showed no perfusion defects in the region of the intermediate
      lesion. At angiography, FFR was determined distal to the intermediate lesion. FFR
      was abnormal (i.e., <0.75) in 15 of 107 stenoses (14%). Angioplasty of the
      intermediate stenosis was deferred based on the absence of a perfusion defect.
      Patients were followed for 1 year to document major cardiac events related to the
      intermediate lesion. At 1-year follow-up, a total of 12 (11%: no deaths, 3
      myocardial infarctions, 2 coronary bypass operations, 7 coronary angioplasties)
      events occurred in the entire group that were related to the intermediate lesion.
      The event rate was significantly higher when angioplasty was deferred despite FFR
      <0.75 compared with the group with FFR > or = 0.75 (4 of 15 [27%] vs 8 of 92
      [9%]; p <0.041). The relative risk of FFR for predicting cardiac events (mainly
      revascularization procedures) was 3.1 (95% confidence interval 1.1 to 8.9; p
      <0.05). In conclusion, deferral of angioplasty of intermediate coronary
      narrowings is safe based on FFR > or = 0.75 in this patient cohort; this
      coincides with previous reports in patients with 1-vessel CAD. Furthermore, these
      results suggest that FFR is more useful than single-photon emission computed
      tomography for clinical decision-making and risk stratification in patients with
      multivessel CAD.

PMID- 11835915
TI  - Timing of aspirin administration as a determinant of survival of patients with
      acute myocardial infarction treated with thrombolysis.
AB  - Unlike thrombolytic agents, there are conflicting data regarding the time
      dependent effect of aspirin treatment on outcome in acute myocardial infarction
      (AMI). We sought to evaluate the impact of timing of aspirin administration
      (before vs after thrombolysis) on mortality of patients with AMI. Our study
      included 1,200 patients with ST elevation AMI treated with thrombolysis. Early (n
      = 364) versus late (n = 836) users were defined as those receiving emergency
      aspirin before versus after initiation of thrombolysis, respectively. Time
      (median) from symptom onset to initiation of aspirin treatment was significantly
      shorter in early versus late users (1.6 vs 3.5 hours; p <0.001). There were no
      significant differences between the 2 groups with respect to baseline clinical
      characteristics. Early aspirin users were more likely to develop reischemia, to
      be treated with beta blockers, to be referred to coronary angiography,
      percutaneous transluminal coronary angioplasty, or coronary artery bypass graft
      surgery. Early users experienced lower mortality at 7 days (2.5% vs 6.0%, p =
      0.01), 30 days (3.3% vs 7.3%, p = 0.008), and 1 year (5.0% vs 10.6%, p = 0.002)
      than late users. This survival benefit persisted for patients with and without
      previous aspirin therapy or revascularization and after adjustment for baseline
      characteristics and therapies at 7 days (odds ratio 0.36, 95% confidence interval
      0.15 to 0.79), at 30 days (odds ratio 0.39, 95% confidence interval 0.17 to
      0.82), and at 1 year (odds ratio 0.41, 95% confidence interval 0.21 to 0.74). Our
      study proposes a time-dependent benefit from aspirin in patients with AMI treated
      with thrombolysis.

PMID- 11835916
TI  - Effects of atorvastatin on oxidized low-density lipoprotein, low-density
      lipoprotein subfraction distribution, and remnant lipoprotein in patients with
      mixed hyperlipoproteinemia.
AB  - Atorvastatin (10 to 20 mg/day) was administered for 3 months to 15 outpatients
      (average age 58 +/- 4 years) with hypercholesterolemia accompanied by
      hypertriglyceridemia without hypolipemic treatment. Changes in lipid profile,
      particularly oxidized low-density lipoprotein (LDL) (malondialdehyde LDL),
      subfractions of LDL, and remnant lipoprotein (RLP) cholesterol, were examined
      before and after administration. In addition, the influence of atorvastatin on
      lipoprotein(a) (known to be an independent risk factor for atherosclerosis),
      asymmetric dimethylarginine (known to be an endogenous inhibitor of nitric oxide
      synthase), and homocysteine (methionine metabolite) was also investigated.
      Administration of atorvastatin significantly decreased serum total cholesterol,
      LDL cholesterol, and triglycerides. Conversely, a significant increase in high
      density lipoprotein cholesterol was shown. In LDL subfractions, large, buoyant
      LDL fractions were not influenced by treatment with atorvastatin (before
      administration, 99 +/- 14 mg/dl; after administration, 91 +/- 6 mg/dl, shown as a
      cholesterol content in each subfraction), but a marked decrease in small, dense
      LDL fractions (p <0.001) (before administration, 119 +/- 17 mg/dl; after
      administration, 43 +/- 10 mg/dl) was shown. Moreover, oxidized LDL was
      significantly decreased (p < 0.01) (before administration, 169 +/- 13 U/L; after
      administration, 119 +/- 10 U/L) and RLP cholesterol also was significantly
      decreased (p <0.01) (before administration, 11.9 +/- 2.0 mg/dl; after
      administration, 6.0 +/- 0.9 mg/dl) with atorvastatin treatment. No significant
      change was observed in fasting plasma glucose, hemoglobin A1c, lipoprotein(a),
      asymmetric dimethylarginine, homocysteine, and so on. These data suggest that
      administration of relatively low doses of atorvastatin to patients with
      hypercholesterolemia accompanied with hypertriglyceridemia results in a decrease
      not only in LDL cholesterol and triglycerides, but also in oxidized LDL and RLP
      cholesterol, with an increase in high-density lipoprotein cholesterol.
      Furthermore, small, dense LDL decreased with a shift in LDL subfractions to
      large, buoyant fractions, and these changes are considered to be involved in the
      inhibition of the onset and progression of atherosclerosis.

PMID- 11835917
TI  - Tolerability of statin-fibrate and statin-niacin combination therapy in
      dyslipidemic patients at high risk for cardiovascular events.
AB  - Achieving recommended cholesterol and triglyceride targets for the prevention of
      cardiovascular events is difficult and frequently requires the use of >1 lipid
      lowering medication. This study evaluated the tolerability and effectiveness of
      combination regimens in high-risk dyslipidemic patients resistant to monotherapy.
      A retrospective chart review of all patients referred to a cardiovascular risk
      reduction clinic over a 7.5-year period identified 136 patients who received
      combination therapy with a 3-hydroxy-3-methylglutaryl coenzyme A reductase
      inhibitor (statin) plus fibrate (n = 106) or a statin plus niacin (n = 30)
      regimen. During follow-up (mean 18.5 months), 28 patients (20.6%) discontinued
      combination therapy: 11 (8.1%) experienced myalgia with or without elevated
      creatine kinase, 3 had gastrointestinal upset, and 1 had asymptomatic creatine
      kinase elevation. No patient had combination therapy discontinued due to elevated
      liver enzymes. Medications were stopped in 8 patients for reasons other than
      reported adverse effects or biochemical abnormalities, and 5 patients were
      switched to alternate monotherapy. Mean percent change from baseline to treatment
      with combination therapy for total cholesterol (-35%), low-density lipoprotein
      cholesterol (-37%), high-density lipoprotein cholesterol (+23%), triglycerides (
      62%), and total cholesterol/high-density lipoprotein cholesterol ratio (-41%)
      were all statistically significant (p <0.01). These results demonstrate that
      combination statin-fibrate and statin-niacin regimens are safe and effective in
      managing dyslipidemias in most patients at risk for cardiovascular events who are
      inadequately treated with one of these agents alone.

PMID- 11835918
TI  - Effect of age and overweight on the QT interval and the prevalence of long QT
      syndrome in children.
AB  - The change in QT interval with age during childhood of normal children and
      children with long QT syndrome (LQTS) and the effects of body mass index on the
      QT interval have not been studied in detail. The prevalence of LQTS in children
      is not well known. We measured 3 consecutive QT and RR intervals in 4,655
      children. Their electrocardiograms along with their height and weight were
      recorded when they were in the first grade in 1994 and again when they were in
      the seventh grade in 2000. The QT interval was corrected by Bazett's formula. The
      longer corrected QT intervals in female subjects than male subjects start at
      elementary school age, earlier than previously reported. Overweight did not have
      an impact on the uncorrected or corrected QT interval. None of the 4 children
      diagnosed with LQTS in the seventh grade had characteristic electrocardiographic
      findings of LQTS in the first grade. All 4 are nonfamilial cases. The prevalence
      of LQTS in children was found to be 1 of 1,164. These data suggest that abnormal
      electrocardiographic phenotypes in children with nonfamilial LQTS may appear
      during the elementary school year. The longer QT intervals in female subjects
      than male subjects start at the same period. No correlation was found between
      obesity and length of the QT interval. Finally, the prevalence of LQTS in
      children is greater than previously suspected.

PMID- 11835919
TI  - Correlates of pulse pressure reduction during antihypertensive treatment
      (losartan or atenolol) in hypertensive patients with electrocardiographic left
      ventricular hypertrophy (the LIFE study).
AB  - In hypertensive patients, pulse pressure has been related to hypertension-induced
      target organ damage and risk of cardiovascular events. However, correlates of
      pulse pressure reduction during antihypertensive treatment have been less
      extensively investigated. We related pulse pressure changes to clinical and
      echocardiographic findings before and after 2 years of antihypertensive treatment
      in 767 patients aged 55 to 80 years (mean 66) in the Losartan Intervention For
      End point reduction in hypertension study. Over 2 years, blood pressure and pulse
      pressure were reduced from 173/98 to 147/84 mm Hg and from 75 to 63 mm Hg,
      respectively, both p <0.001. In linear multivariate analysis controlling for
      initial pulse pressure, 2-year reduction in pulse pressure correlated negatively
      with age and concomitant diabetes mellitus, and positively with body height and 2
      year reduction in mean blood pressure (multiple R(2) = 0.42, p <0.01). When
      dividing the study population into 2 groups using a prognostically validated
      partition for pulse pressure, patients with pulse pressure > or =63 mm Hg after 2
      years of antihypertensive treatment (n = 349) were older and shorter, included
      more women and patients with isolated systolic hypertension, diabetes mellitus,
      albuminuria, and echocardiographic left ventricular hypertrophy at baseline, and
      also had a smaller decrease in mean blood pressure and the urinary
      albumin/creatinine ratio over 2 years (all p <0.05). Thus, in hypertensive
      patients with electrocardiographic left ventricular hypertrophy, older age, less
      reduction in mean blood pressure, concomitant diabetes mellitus, and shorter
      stature are associated with attenuated pulse pressure reduction during
      antihypertensive treatment.

PMID- 11835920
TI  - Relation of aldosterone "escape" despite angiotensin-converting enzyme inhibitor
      administration to impaired exercise capacity in chronic congestive heart failure
      secondary to ischemic or idiopathic dilated cardiomyopathy.
AB  - In patients with chronic congestive heart failure (CHF), aldosterone production
      may occur despite the administration of angiotensin-converting enzyme (ACE)
      inhibitors. This phenomenon has been termed aldosterone "escape"; its relation to
      the severity of the disease is unknown. We sought to assess whether aldosterone
      escape might be related to disease severity or functional impairment in patients
      with CHF. One hundred forty-one consecutive patients with CHF who received ACE
      inhibitors (> 6 months) underwent an evaluation of neurohormonal activation and
      body composition, an echo-Doppler examination, and a cardiopulmonary exercise
      test. Aldosterone escape was defined as plasma levels of aldosterone above the
      normal range in our laboratory (> 0.42 nmol/L). Fourteen patients (10%) had
      aldosterone escape. There were no differences between patients with and without
      aldosterone escape with regard to age, New York Heart Association class,
      neurohormonal activation, ACE inhibitor dose, hemodynamics, or skeletal muscle
      bulk. In contrast, mean peak oxygen consumption (14.2 +/- 3.5 vs 17.3 +/- 4.9
      ml/min/kg, p < 0.05) and the slope of the relation between ventilation and carbon
      dioxide production (41 +/- 7 vs 36 +/- 6, p <0.05) were significantly worse in
      patients with aldosterone escape compared with those without it. Thus,
      aldosterone escape is associated with reduced exercise capacity in patients with
      CHF. This factor does not seem to be linked with hemodynamic mechanisms or with a
      reduced skeletal muscle bulk.

PMID- 11835921
TI  - Regression of left ventricular mass one year after aortic valve replacement for
      pure severe aortic stenosis.
AB  - The aim of the study was to quantify a 1-year change in left ventricular (LV)
      mass index (MI) and systolic LV function in 30 patients with pure severe aortic
      stenosis by means of serial 3-dimensional (3-D) echocardiography. To assess the
      completeness of LVMI regression after 1 year, we compared the postoperative mass
      of patients with mass values of 30 normotensive control subjects without a
      history of cardiac disease. Ejection fraction increased from 64 +/- 14% before
      surgery to 69 +/- 8% at follow-up (p = 0.067), and functional class improved from
      2.9 +/- 0.5 to 1.4 +/- 0.5 (p <0.05), with improvement in each patient. During
      the same period, LVMI regressed by 23.4% (p <0.001). Postoperative LVMI was
      related to preoperative LVMI (r = 0.82; p <0.001) and baseline ejection fraction
      (r = -0.5; p = 0.009). LVMI regressed into the normal range in 64% of patients at
      follow-up. Patients achieving normal mass values did not differ with respect to
      patient gender, valve type, or valve size. Patients with reduced preoperative LV
      function had larger volumes (p <0.01), larger mass values (p <0.01), and a trend
      toward more mass regression (p = 0.062) than patients with normal preoperative
      function. Although ejection fraction improved after 1 year in all of these
      patients (p <0.03), they were less likely to achieve normal mass values at follow
      up (p = 0.01). Regression of LVMI in patients with pure aortic stenosis is a
      positive event that occurs in each patient and that is associated with
      improvement in functional status. LVMI regressed into the normal range in most
      patients with normal preoperative function. Preoperative LV function, but not
      patient gender, valve type, or size, was related to normalization of LVMI at
      follow-up in this selected study population.

PMID- 11835922
TI  - Power-law behavior of heart rate variability in Chagas' disease.
AB  - Beta slope is a nonlinear index derived from the power-law analysis of 24-hour
      heart rate variability (HRV); in healthy subjects, the beta index is typically
      near -1, suggesting a fractal behavior of HRV. There is scarce data on HRV in
      Chagas' disease. This transversal study intends to describe power-law and linear
      HRV patterns in different forms of Chagas' disease. Patients and healthy controls
      (n = 26) without other diseases were submitted to a standardized protocol,
      including electrocardiography, echocardiography, and 24-hour Holter monitoring.
      Patients with Chagas' disease were divided into groups according to their left
      ventricular (LV) systolic function: normal (group 1, n = 85), segmental
      abnormalities (group 2, n = 49), and reduced ejection fraction (group 3, n = 26).
      The temporal series were carefully processed to obtain the HRV indexes and beta
      slope. Despite the differences in the LV systolic function, the 3 groups were
      comparable in terms of long-term HRV index values. After adjustment for
      covariates, short-term HRV index values were consistently reduced in the Chagas'
      disease groups. The beta-index values were also diminished in Chagas' disease
      groups (group 1: -1.09 +/- 0.03, group 2: -1.11 +/- 0.06; group 3: -1.14 +/-
      0.03; and controls: 0.95 +/- 0.03, p <0.001). This breakdown of fractal long
      range correlation of RR interval dynamics, a strong predictor of mortality in
      other cardiomyopathies, may reflect cardiac dysautonomia that may have gone
      undetected in long-term time-domain analysis. This abnormality may explain the
      increased risk for arrhythmic sudden death found in Chagas' disease even in the
      absence of signs of LV dysfunction.

PMID- 11835923
TI  - Inflammation and coagulation factors in persons > 65 years of age with symptoms
      of depression but without evidence of myocardial ischemia.
AB  - Depression is associated with increased cardiovascular disease, but the
      underlying mechanisms are not well understood. This study examines associations
      of depressive symptoms with inflammation and coagulation factors in persons aged
      > 65 years. Blood samples were obtained from 4,268 subjects free of
      cardiovascular disease (age 72.4 +/- 5.5 years, 2,623 women). Inflammation
      markers were C-reactive protein (CRP), white blood cell (WBC) count, total
      platelet count, and albumin; coagulation factors included factors VIIc and VIIIc
      and fibrinogen. Depression was assessed with the Center for Epidemiologic Studies
      Depression scale, and states of energy depletion with a validated exhaustion
      index. Statistical adjustments were made for risk factors (age, sex, race,
      systolic blood pressure, smoking status, diabetes mellitus) and physical measures
      of frailty (isometric handgrip, timed 15-feet walk test, activity level).
      Depression was associated with elevated CRP (3.31 +/- 0.10 vs 3.51 +/- 0.21
      mg/L), WBC (6.14 +/- 0.03 vs 6.43 +/- 0.11 10(6)/L), fibrinogen (319 +/- 1 vs 326
      +/- 3 mg/dl), and factor VIIc (124.6 +/- 0.6% vs 127.2 +/- 1.3%; all p <0.05).
      Exhaustion also was related to elevated inflammation and coagulation markers (p <
      0.05). Exhausted men had markedly elevated CRP levels (6.82 +/- 2.10 mg/L) versus
      nonexhausted men (3.05 +/- 0.16: p = 0.007). After adjustment for control
      variables, exhaustion remained associated with albumin (p = 0.033), fibrinogen (p
      = 0.017), CRP (p = 0.066), and WBC (p = 0.060), whereas associations of
      depressive symptoms with biochemistry measures lost statistical significance.
      Thus, depression and exhaustion are associated with low-grade inflammation and
      elevated coagulation factors in persons aged > 65 years.

PMID- 11835924
TI  - Comparison of thromboembolic events in patients treated with celecoxib, a
      cyclooxygenase-2 specific inhibitor, versus ibuprofen or diclofenac.
AB  - It has been hypothesized that cyclooxygenase 2 specific inhibitors may increase
      the risk of cardiovascular (CV) thromboembolic events because of their inhibition
      of vascular prostacyclin synthesis and lack of an effect on platelet thromboxane
      A(2) production and aggregation. Thus, we analyzed the data for celecoxib and
      nonsteroidal anti-inflammatory drugs (NSAIDs) from the Celecoxib Long-term
      Arthritis Safety Study to determine the incidences of serious CV thromboembolic
      events. This trial included 3,987 persons randomized to celecoxib 400 mg twice
      daily (2,320 person-years of exposure) and 3,981 persons randomized to either
      ibuprofen 800 mg 3 times daily or diclofenac 75 mg twice daily (2,203 person
      years). Because acetylsalicylic acid (ASA) use for CV risk prophylaxis (< or =325
      mg/day) was permitted, separate analyses were performed for all patients and
      those not taking ASA. The incidences of serious CV thromboembolic events
      (myocardial infarction, stroke, CV deaths, and peripheral events) were similar,
      and not significantly different, between celecoxib and NSAID comparators
      (combined or individually) for all patients as well as the subgroup of patients
      not taking ASA. This observation was true both for all serious CV thromboembolic
      events, as well as for individual events. No increase in myocardial infarction
      was apparent, even in patients not taking ASA who were candidates for secondary
      prophylaxis for myocardial infarction. The relative risks for celecoxib versus
      NSAIDs for serious CV thromboembolic events were 1.1 for all patients and 1.1 for
      the subgroup of patients not taking ASA (95% confidence interval 0.7 to 1.6 and
      0.6 to 1.9, respectively). In addition, the incidences of adverse CV events such
      as hypertension, edema, and congestive heart failure were similar to, or
      significantly lower than, NSAID comparators regardless of the use of ASA. Thus,
      these analyses demonstrate no increased risk of serious CV thromboembolic events
      associated with celecoxib compared with conventional NSAIDs and therefore do not
      support the hypothesis of a class adverse effect of cyclooxygenase 2 specific
      inhibitors on the CV system.

PMID- 11835925
TI  - Effect of insulin therapy on endothelium-dependent dilation in type 2 diabetes
      mellitus.
AB  - Endothelial dysfunction is an early marker of atherosclerosis occurring in
      patients with type 2 diabetes mellitus. Endothelium-dependent dilation (EDD) has
      been shown to improve by combined therapy of insulin and metformin. Studies on
      endothelium-independent vasodilatory capacity, however, have had controversial
      results. We sought to investigate the vascular reactivity--EDD and endothelium
      independent dilation--and their changes induced by the addition of insulin
      therapy to patients with type 2 diabetes mellitus pretreated with diet and oral
      hypoglycemic drugs. We therefore performed vascular studies in 21 poorly
      controlled type 2 diabetic patients and 11 nondiabetic control subjects by using
      high resolution ultrasound of the brachial artery. After 3 months of additional
      insulin therapy, vascular and laboratory measurements including C-reactive
      protein and parameters of glucose and lipoprotein metabolism were repeated. At
      baseline, EDD was significantly impaired in diabetic patients compared with
      controls (2.7 +/- 2.2% vs 7.0 +/- 1.8%, p <0.001), whereas endothelium
      independent dilation was normal in both groups. After insulin therapy, EDD
      increased from 2.7 +/- 2.2% to 5.0 +/- 2.8% (p <0.001) in diabetic patients. All
      other vascular parameters did not change over the treatment period. The absolute
      change in EDD showed a significant negative correlation with the change in
      hemoglobin A(1c) (r = -0.67, p <0.001) and with fasting blood glucose (r = -0.84,
      p <0.001) levels. In contrast, there was no correlation between EDD and the
      observed changes in lipid and C-reactive protein levels. Our findings demonstrate
      that insulin therapy has beneficial effects on vascular function, resulting in
      enhanced EDD, most probably due to an improved glycemic control as the underlying
      mechanism.

PMID- 11835926
TI  - Watkins Proctor Harvey, MD: a conversation with the editor.

PMID- 11835927
TI  - Comparison of efficacy and complication rates after percutaneous coronary
      interventions in patients with and without renal insufficiency treated with
      abciximab.

PMID- 11835928
TI  - Resolution of ST-segment elevation following intravenous administration of
      nitroglycerin and verapamil.

PMID- 11835929
TI  - Different circumstances, timing, and symptom presentation at onset of Q-wave
      versus non-Q-wave acute myocardial infarction.

PMID- 11835930
TI  - Changes in plasma lipids and low-density lipoprotein peak particle size during
      and after acute myocardial infarction.

PMID- 11835931
TI  - Prognostic value of N-terminal pro-atrial and pro-brain natriuretic peptide in
      patients with acute coronary syndromes.

PMID- 11835932
TI  - Intravascular ultrasound assessment of spontaneous coronary artery dissection.

PMID- 11835933
TI  - Effects of simvastatin (40 and 80 mg) on highly sensitive C-reactive protein in
      patients with combined hyperlipidemia.

PMID- 11835934
TI  - Analysis of age of onset of accessory pathway-mediated tachycardia in men and
      women.

PMID- 11835935
TI  - Clinical outcomes of children with normal cardiac anatomy having radiofrequency
      catheter ablation > or =10 years earlier.

PMID- 11835936
TI  - Association of diverticular disease of the colon and vagal atrial fibrillation.

PMID- 11835937
TI  - Prevalence of cytomegalovirus in nonrheumatic stenotic aortic valves.

PMID- 11835938
TI  - Continuous-wave Doppler echocardiographic evaluation of the changes in pulmonary
      arterial pressure during the first seven days of life.

PMID- 11835939
TI  - Cervical origin of the subclavian artery as a specific marker for monosomy 22q11.

PMID- 11835940
TI  - Effect of the "Race Across The Alps" in elite cyclists on plasma cardiac
      troponins I and T.

PMID- 11835942
TI  - Persistent myocardial sinusoids of the left ventricle.

PMID- 11835941
TI  - A novel deletion mutation in the cardiac myosin-binding protein C gene as a cause
      of Maron's type IV hypertrophic cardiomyopathy.

PMID- 11835944
TI  - Effect of red versus white wine on the heart.

PMID- 11835945
TI  - Deletion allele of the angiotensin-converting enzyme gene as a risk factor for
      pneumonia in elderly patients.
AB  - PURPOSE: Aspiration due to an age-related reduction in cough is a major cause of
      pneumonia in elderly persons. Because the insertion/deletion (I/D) polymorphism
      of the angiotensin-converting enzyme (ACE) gene (ACE) has been associated with
      the cough reflex, we studied whether this genetic polymorphism was also
      associated with the risk of pneumonia. SUBJECTS AND METHODS: We studied 1011
      elderly inpatients (221 men and 790 women, mean [+/- SD] age of 82 +/- 7 years)
      in a long-term care hospital. The association between the ACE I/D polymorphism
      and the incidence of pneumonia (defined using specific criteria that included
      radiographic abnormalities) was assessed during an 8-month period that excluded
      the winter. Data were analyzed using proportional hazards models, with adjustment
      for age, sex, and other potential confounders. RESULTS: During follow-up, 87
      cases (9%) of pneumonia occurred, 38 of which were fatal. The ACE DD allele (vs.
      ID + II) was associated with an increased risk of pneumonia (relative risk [RR] =
      2.9; 95% confidence interval [CI]: 1.7 to 4.8, P < 0.001) and fatal pneumonia [RR
      = 4.4; 95% CI: 2.1 to 9.0; P < 0.0001). CONCLUSIONS: The ACE D allele is an
      independent risk factor for pneumonia in elderly persons.

PMID- 11835946
TI  - Triage of patients with chest pain in the emergency department: a comparative
      study of physicians' decisions.
AB  - PURPOSE: Little is known about physicians' triage decisions for patients with
      chest pain in the emergency department. We sought to understand better the
      variability and accuracy of physicians' triage decisions. SUBJECTS AND METHODS:
      We used 20 simulated cases to compare triage decisions by 147 physicians (46
      emergency medicine, 87 internal medicine, and 14 cardiology physicians) with
      triage decisions recommended by a previously validated prediction rule. We
      calculated triage sensitivity and specificity using the prediction rule to
      estimate the likelihood that each of the simulated patients would suffer a major
      complication. Triage sensitivity was defined as the proportion of all patients
      expected to have major complications who were triaged to the coronary care or
      inpatient telemetry unit. RESULTS: Triage specificity was defined as the
      proportion of all patients without complications who were triaged to sites other
      than the coronary care or inpatient telemetry unit.Physicians' triage decisions
      were less sensitive (85% vs. 96%, P <0.001) and less specific (38% vs. 41%, P =
      0.02) than decisions recommended by the prediction rule. Physicians overestimated
      patients' risk of complications and triaged more patients to inpatient monitored
      beds. Despite their preference for inpatient monitored beds, physicians'
      decisions would have resulted in four times as many major complications in
      patients who were not triaged to inpatient monitored beds, compared with
      decisions recommended by the prediction rule (2.4% vs. 0.6%, P <0.001). Although
      physicians' decisions were best explained by their provisional diagnoses,
      interphysician agreement about triage decisions (kappa = 0.34) and diagnosis
      (kappa = 0.31) was only fair. CONCLUSIONS: In simulated cases, physicians' triage
      decisions varied widely and their predictions of patient outcomes differed
      markedly from that of the validated prediction rule, suggesting that use of the
      prediction rule in the emergency department could improve physicians' decisions
      and patients' outcomes.

PMID- 11835947
TI  - Trends in the incidence of coronary heart disease and stroke and the prevalence
      of cardiovascular risk factors among Japanese men from 1963 to 1994.
AB  - PURPOSE: To determine trends in the incidence of cardiovascular disease in Japan,
      we examined observational data on coronary heart disease, stroke, and
      cardiovascular risk factors among urban Japanese working men. SUBJECTS AND
      METHODS: The surveyed population included all male employees aged 40 to 59 years
      who worked for eight industrial companies in Osaka, the second largest
      metropolitan city in Japan. Surveillance for cardiovascular disease and risk
      factors was conducted from 1963 to 1994. RESULTS: The age-adjusted incidence of
      coronary heart disease increased from 0.4 per 1000 person-years during 1963 to
      1970, to 1.5 per 1000 person-years during 1979 to 1986, and then plateaued until
      1987 to 1994 (P for trend = 0.002), whereas the incidence of stroke declined from
      1.2 per 1,000 person-years during 1971 to 1978, to 0.6 per 1,000 person-years in
      1987 to 1994 (P for trend = 0.02). The age-adjusted mean (+/- SD) total
      cholesterol level, which was 4.87 +/- 2.88 mmol/L during 1963 to 1966, increased
      to 5.11 +/- 0.62 mmol/L during 1982 to 1983 (P <0.001), and 5.09 +/- 0.75 mmol/L
      during 1990 to 1991. Both mean systolic and diastolic blood pressures increased
      by 1 mm Hg between the periods of 1966 to 1967 and 1982 to 1983, and declined
      below the 1966 to 1967 levels during 1990 to 1991. The prevalence of smoking
      declined from 72% during 1975 to 1976, to 58% during 1990 to 1991 (P for trend
      <0.001). CONCLUSION: Although these findings were limited to urban middle-aged
      men, the increase in serum cholesterol is likely to attenuate the reduction in
      future rates of coronary heart disease in Japan that would have been expected to
      result from the declining prevalence of smoking.

PMID- 11835948
TI  - Renin-angiotensin system blockade and the risk of hyperkalemia in chronic
      hemodialysis patients.
AB  - BACKGROUND: Blockade of the renin-angiotensin system by angiotensin-converting
      enzyme (ACE) inhibitors or angiotensin receptor blockers can cause hyperkalemia
      in patients with chronic renal insufficiency who are not on dialysis, but the
      risk of hyperkalemia in hemodialysis patients is unknown. SUBJECTS AND METHODS:
      We conducted a prospective study of 251 adult hemodialysis patients to determine
      if renin-angiotensin system blockade was associated with hyperkalemia, defined as
      a predialysis serum potassium concentration of 5.5 mmol/L or higher. Medication
      use was determined by chart review and patient interview. Predialysis serum
      potassium concentration was measured monthly. RESULTS: There were 367 episodes of
      hyperkalemia during 1877 person-months of follow-up. After adjustment for
      potential confounding variables and for clustering of episodes by patient, use of
      an ACE inhibitor or an angiotensin receptor blocker was associated with a
      significantly higher risk of hyperkalemia (odds ratio [OR] = 2.2; 95% confidence
      interval [CI]: 1.4 to 3.4). The increased risk of hyperkalemia with renin
      angiotensin system blockade was seen in anuric dialysis patients (OR = 2.3; 95%
      CI: 1.3 to 4.2), as well as those with residual renal function (OR = 2.1; 95% CI:
      1.0 to 4.1). CONCLUSION: The use of ACE inhibitors or angiotensin receptor
      blockers is independently associated with an increased risk of developing
      hyperkalemia in chronic hemodialysis patients. The serum potassium concentration
      should be closely monitored when these medications are prescribed for
      hemodialysis patients.

PMID- 11835949
TI  - Prognosis of patients who develop acute renal failure during the first 24 hours
      of cardiogenic shock after myocardial infarction.
AB  - PURPOSE: Acute renal failure has important prognostic implications in critically
      ill patients, but the effects of acute renal failure on in-hospital mortality in
      the subset of patients with cardiogenic shock are not known. SUBJECTS AND
      METHODS: All consecutive patients who presented with acute coronary syndrome at
      our cardiovascular intensive care unit from 1993 to 2000 and who were in
      cardiogenic shock were enrolled. Acute renal failure was defined as a urine
      volume < 20 mL/h associated with an increase in serum creatinine level > or = 0.5
      mg/dL or > 50% above the baseline value. RESULTS: There were 118 patients (83 men
      [70%]; mean [+/- SD] age, 66 +/- 10 years), 39 (33%) of whom developed acute
      renal failure within 24 hours after the onset of shock. In-hospital mortality was
      87% (34/39) in patients with acute renal failure and 53% (42/79) in patients
      without acute renal failure (odds ratio [OR] = 6.0; 95% confidence interval [CI]:
      2.1 to 17; P < 0.001). Other significant univariate predictors of mortality
      included the peak serum lactate level, epinephrine dose, and the maximum serum
      creatinine level. Multivariate logistic regression analysis identified acute
      renal failure as the only independent predictor of mortality. CONCLUSION: Acute
      renal failure was common in patients with cardiogenic shock and strongly
      associated with in-hospital mortality.

PMID- 11835950
TI  - The impact of follow-up physician visits on emergency readmissions for patients
      with asthma and chronic obstructive pulmonary disease: a population-based study.
AB  - PURPOSE: To examine the relation between follow-up office visits after emergency
      discharge and the risk of emergency readmissions in patients with asthma or
      chronic obstructive pulmonary disease (COPD). SUBJECTS AND METHODS: We used
      population-based data to identify all patients in Alberta, Canada, who had at
      least one emergency visit for asthma or COPD between April 1, 1996, and March 31,
      1997 (N = 25 256). A Cox proportional hazards model was used to estimate the
      adjusted relative risk (RR) of a repeat visit to an emergency department within
      90 days of an initial emergency visit in patients who did or did not have an
      office follow-up within the first 30 days. RESULTS: There were 7829 patients
      (31%) who had an office visit during the 30 days after their initial emergency
      encounter. Follow-up visits were associated with a significant reduction in the
      90-day risk of an emergency readmission (RR = 0.79; 95% confidence interval [CI]:
      0.73 to 0.86). Sensitivity analyses showed that a follow-up visit was inversely
      associated with a repeat emergency visit after adjusting for age, sex, area of
      residence, and income. CONCLUSION: Although these data should be interpreted with
      caution because of missing information on factors such as quality of care, they
      suggest that follow-up office visits are effective in reducing early relapses in
      patients who have been recently treated in emergency departments for asthma or
      COPD.

PMID- 11835951
TI  - Potential indications for angiotensin-converting enzyme inhibitors in
      atherosclerotic vascular disease.
AB  - Angiotensin-converting enzyme (ACE) inhibitors are well established as first-line
      therapy for patients with left ventricular dysfunction, diabetic patients with
      hypertension or renal disease, and patients recovering from myocardial
      infarction. Angiotensin II and bradykinin regulate cellular proliferation,
      inflammation, and endothelial function, thus playing an important role in the
      pathogenesis of atherosclerosis. A large body of experimental evidence reporting
      that ACE inhibitors limit these effects has formed the rationale for major
      clinical trials of these drugs in the management of atherosclerotic vascular
      disease. The first trial to be completed demonstrated that ACE inhibition
      improves the prognosis of patients who have, or are at risk of, atherosclerotic
      vascular disease, independent of its effects on left ventricular function and
      hypertension. Expanding the indications for ACE inhibitors is now evidence
      driven, although the choice of agent for these new indications remains to be
      determined by further research.

PMID- 11835952
TI  - The safety of triptans in the treatment of patients with migraine.
AB  - The introduction of the triptans (5-hydroxytryptophan [5-HT] (1B/1D) agonists) in
      the past decade has brought migraine-specific pain relief to those suffering from
      migraine. These drugs activate the serotonin receptors 5-HT(1B) and 5-HT(1D) on
      cerebral vessels. Concerns about their safety, particularly in patients with
      vascular risk factors, have been raised because triptans also activate the 5
      HT(1B) receptors on coronary arteries. Although triptans are contraindicated in
      patients with cardiac or cerebrovascular disease, they are safer than many other
      medications used to treat patients with migraine, including the nonspecific
      serotonin-agonist ergot preparations.

PMID- 11835953
TI  - Effect of genotypic differences in interleukin-1 beta on gastric acid secretion
      in Japanese patients infected with Helicobacter pylori.

PMID- 11835954
TI  - Open heart surgery in the elderly: results from a consecutive series of 100
      patients aged 85 years or older.

PMID- 11835955
TI  - Does mefloquine prophylaxis affect electroencephalographic patterns?

PMID- 11835956
TI  - Manipulating the renin-angiotensin system: more than we bargained for?

PMID- 11835957
TI  - Navigating the scylla and charybdis of chest pain management in the emergency
      department. Is a computer the answer?

PMID- 11835959
TI  - Limitations of a meta-analysis investigating the association between cancer and
      statin use.

PMID- 11835960
TI  - Body weight and response to vitamin K administration.

PMID- 11835962
TI  - Clinics for adults with hereditary metabolic diseases.

PMID- 11835963
TI  - Hypocalcemic tetany as an early sign of DiGeorge syndrome in an adult woman.

PMID- 11835964
TI  - Whiplash--review of a commonly misunderstood injury.

PMID- 11835965
TI  - Hashimoto's disease presenting as encephalitis in a young woman.

PMID- 11835966
TI  - Improving the quality of health care in America: what medical schools, leading
      medical journals, and federal funding agencies can do.

PMID- 11835968
TI  - The evolution of monogenean diversity.
AB  - The Monogenea are an ideal group for investigations of the processes behind their
      past diversification and their present diversity for at least three reasons: they
      are diverse both in terms of morphology and numbers, they are generally host
      specific, and their phylogeny is well resolved, at least to the family level. The
      present investigation takes a broad look at monogenean diversity in order to try
      to determine whether the diversification of monogeneans is driven by some
      ecological features of the parasites themselves, or by extrinsic factors
      associated with their hosts. First, our current knowledge of monogenean diversity
      appears good enough to warrant investigation into its evolution. The body size of
      new species correlates negatively with their year of description both generally
      and within given families, i.e. it decreases over time in a way that suggests
      that only some of the smallest species are left to be discovered. Second, the
      occurrence of congeneric monogenean species on the same host species is not
      associated with host body size, once phylogenetic influences are controlled. This
      analysis suggests that host size is not one of the factors promoting local
      diversification of monogenean taxa. Third, the species richness of the different
      monogenean families does not correlate with the average body size of their
      members. Thus, this basic parasite life-history trait is not a determinant of
      diversification rates. Combined, the results of these separate analyses provide
      preliminary answers to some of the big questions concerning the diversification
      of monogeneans, but leave many other questions unanswered. The phylogenetic
      analytical framework adopted here should allow these questions to be tackled once
      the necessary data become available.

PMID- 11835967
TI  - Phylogenetics of the Monogenea--evidence from a medley of molecules.
AB  - Nuclear ribosomal DNA sequences of Monogenea from both complete small and partial
      large (D1-D2) subunits were determined and added to previously published
      sequences in order to best estimate the molecular phylogeny of the group. A total
      of 35 ssrDNA, 100 D1 lsrDNA and 51 D2 lsrDNA monogenean sequences were used,
      representing a total of 27 families. From these sequences different data sets
      were assembled and analysed to make the best use of all available molecular
      phylogenetic information from the taxa. Maximum parsimony and minimum evolution
      trees for each data partition were rooted against published sequences from the
      Cestoda, forcing the Monogenea to appear monophyletic. There was broad agreement
      between tree topologies estimated by both methods and between genes. Well
      supported nodes were restricted to deeply diverging major groupings and more
      derived taxa with the lsrDNA data but were at most nodes with ssrDNA. The
      Polyonchoinea showed the greatest resolution with a general pattern of
      ((Monocotylidae(Capsalidae(Udonellidae+Gyrodactylidea)))((Anoplodiscidae+Sundanon
      hidae)(Pseudomurraytrematidae+Dactylogyridae))). The Heteronchoinea readily split
      into the Polystomatoinea+Oligonchoinea, and Chimaericolidae and Hexabothriidae
      were successively the most basal of oligonchoinean taxa. Relationships within the
      Mazocraeidea, comprising 27 families of which 15 were sampled here, were largely
      unresolved and appear to reflect a rapid radiation of this group that is
      reflected in very short internal branches for ssrDNA and D1 lsrDNA, and highly
      divergent D2 lsrDNA. A reduced morphological matrix, employing only those
      families represented by molecules, contrasted sharply with respect to
      polyonchoinean interrelationships. Deep branches of the Heteronchoinea were
      similar for both classes of data but also showed that the interrelationships of
      the mazocraeidean families are labile and susceptible to sampling.

PMID- 11835969
TI  - Gyrodactylid developmental biology: historical review, current status and future
      trends.
AB  - In the viviparous gyrodactylids, embryos develop one inside another within the
      parental uterus, a phenomenon with major implications for the biology of this
      species-rich group. Development occurs via two routes: first-born daughters
      develop at the centre of an embryo cluster in utero, whereas all other daughters
      develop from oocytes. The resulting offspring are, however, morphologically
      indistinguishable. We review here the history of gyrodactylid embryology in the
      context of current knowledge and, present additional cytogenetic and
      ultrastructural observations of embryonic development. These progenetic parasites
      are highly modified for viviparity; oocyte maturation and sperm storage occur in
      a single chamber, the Egg Cell Forming Region, and a mature oocyte passes into
      the uterus after the birth of the preceding, fully developed offspring. The
      uterus has a syncytial lining derived from anterior and posterior cap cells.
      These cells are the first to differentiate in the female reproductive system and
      may be involved in controlling development. Embryos receive nutrients via the
      uterus rather than from vitelline cells. Traditionally, development of the first
      born daughter has been considered a form of polyembryony, although paedogenesis
      has also been suggested. In contrast to previous studies, we could not trace
      lineage of the first-born daughter to a single quiescent macromere. However, only
      mitotic divisions have been conclusively observed in the intraembryonic
      generation, indicating an asexual origin. All other daughters are formed from
      meiotically derived oocytes by sexual reproduction or automictic parthenogenesis.
      The latter may involve pre-meiotic doubling of chromosomes, but the precise
      mechanism and the relative proportion of sexual and parthenogenetic offspring are
      unknown. Exceptionally, cleavage in Gyrodactylus spp. occurs by duets rather than
      quartets (a pattern previously only recorded in acoels) and is characterised by
      extensive cell rearrangements. Blastomeres may be connected by fine cytoplasmic
      processes or completely disassociated and are readily redistributed by the
      muscular actions of the parental uterus. This process resembles 'Blastomeren
      Anarchie' of rhabdocoels but without the structural support of vitelline cells.
      It prevents generation of early cell fate maps and indicates regulative, rather
      than mosaic, development. Structures such as the gut and excretory system
      differentiate late, and are highlighted, together with the attachment apparatus,
      as examples of post-embryonic differentiation. Molecular and cellular techniques
      are now essential to further elucidate mechanisms of gyrodactylid reproduction,
      which will in turn contribute to current debates with animal embryology.

PMID- 11835970
TI  - Host specificity dynamics: observations on gyrodactylid monogeneans.
AB  - The directly transmitted viviparous gyrodactylids have high species richness but
      low morphological and biological diversity, and many species are recorded from
      only a single host. They therefore constitute a guild of species ideal for
      studies of the evolutionary significance of host specificity. The group has the
      widest host range of any monogenean family, being found on 19 orders of bony
      fish. However, individual species range from narrowly specific (71% of 402
      described species recorded from a single host) to extremely catholic
      (Gyrodactylus alviga recorded from 16 hosts). Gyrodactylid-host interactions
      extend from 60 mya (G. lotae, G. lucii) down to 150 years (G. derjavini on
      Oncorhynchus mykiss). Co-evolution with the host is comparatively rare within the
      gyrodactylids, but host switching or ecological transfer is common, and has been
      facilitated by the mixing of fish strains that followed glaciation. In this
      review, we consider the factors responsible for gyrodactylid specificity
      patterns, using examples from our work on salmonid gyrodactylids including G.
      salaris, responsible for major epidemics on wild Atlantic salmon (Salmo salar) in
      Norway since 1975, and G. thymalli from grayling and G. derjavini from trout.G.
      salaris has a wide host range with highest population growth rates on Norwegian
      salmon strains. However, growth rates are variable on both host strains and
      species, because of the multitude of micro- and macro-environmental factors
      influencing parasite mortality and fecundity. A better predictor of performance
      is the proportion of fishes of a strain which are innately resistant to the
      parasite, a measure which is negatively correlated with the time to peak
      infection in a host strain. Population growth rate is also negatively correlated
      with age of infection; the initial rate, therefore, predicts best the suitability
      of a fish as host for G. salaris. The host response to gyrodactylids appears to
      be the same mechanism in all salmonids with innate resistance as one end of a
      spectrum, but influenced by stress and probably under polygenic control. Hybrid
      experiments show that performance of G. salaris on a host is heritable, and
      usually intermediate between that of the parents. This host response mechanism,
      coupled with the initial parasite population growth on a fish, determines the
      host specificity, i.e. whether the fish will be susceptible, a responder or
      innately resistant. The use of population growth rate parameters allows
      comparison of different hosts as a resource for a gyrodactylid. In the case of G.
      salaris, East Atlantic and Baltic strains of Atlantic salmon are core hosts, but
      other salmonids can physiologically sustain infections for considerable periods,
      and may be important in parasite dispersal and transmission. A further group of
      non-salmonid fishes are unable to sustain G. salaris reproduction, but can act as
      transport hosts.Population growth parameters are very labile to stressors and
      environmental factors, particularly temperature and salinity, and also other
      aspects of host ecology and water quality. These factors may also influence the
      spectrum of hosts that can be infected under particular conditions, and probably
      favoured ecological transfer of gyrodactylids between host species in periglacial
      conditions. G. salaris may still be undergoing post-glacial range expansion
      (aided by anthropogenic spread) as shown by the increase in the species range
      over the last 25 years. The origin of G. salaris, G. teuchis and G. thymalli is
      discussed in relation to glacial refugiums during the last ice age.

PMID- 11835971
TI  - Interactions between monogenean parasites and their fish hosts.
AB  - Parasite factors associated with recognition and selection of the host and the
      mechanisms in the host responsible for acceptance or rejection of the invading
      organism were evaluated. Sensory structures in parasites are able to detect
      differences between different fish species and this ability to discern between
      fishes may be based on both chemical and mechanical stimuli on the host surface.
      Complex glycoproteins, proteins, carbohydrates and simple molecules attract
      parasites or modify their behaviour. Furthermore, attachment of the monogenean
      parasite to a host is dependent on both mechanical structures and chemical
      factors in the parasite. These systems comprise anterior pads, posterior haptors,
      gland secretions, and muscular elements. The parasite needs access to appropriate
      nutrients which can be absorbed and used for reproduction and in this context
      signals from the host are needed for an optimal physiological response of the
      parasite. The innate and adaptive immune systems of the host are important
      elements in this question. Investigations have indicated that innate host factors
      (complement, lectins, acute phase reactants, macrophages) can bind to monogeneans
      and elicit severe damage to the parasites. The targets for these hostile products
      are not only the monogenean tegument, but may involve the gastrodermis and
      glands. However, the parasite's ability to avoid and even exploit the wide array
      of immunological elements of the host may be an important player in the dynamic
      interactions between host and monogenean determining host specificity. Even fish
      hosts susceptible to a certain parasite show an ability to mount a protective
      response at post-infection periods. Elevation of the host's production of
      adaptive and non-adaptive factors following monogenean infections of a certain
      duration may explain the acquired response.

PMID- 11835972
TI  - Diversity in the Monogenea and Digenea: does lifestyle matter?
AB  - If the cestodes are excluded, then the parasitic platyhelminths of fishes divide
      neatly into the external and monoxenous Monogenea and the internal and
      heteroxenous Digenea. Both groups have apparently had long associations of
      coevolution, host switching and adaptation with fishes and have become highly
      successful in their respective habitats. Current estimates of species richness
      for the two groups suggest that they may be remarkably similar. Here we consider
      the nature of the diversity of the Monogenea and Digenea of fishes in terms of
      richness of species and higher taxa to determine what processes may be
      responsible for observed differences. The Monogenea includes at least two super
      genera (Dactylogyrus and Gyrodactylus) each of which has hundreds of species; no
      comparable genera are found in the Digenea. Possible reasons for this difference
      include the higher host specificity of monogeneans and their shorter generation
      time. If allowance is made for the vagaries of taxonomic 'lumping' and
      'splitting', then there are probably comparable numbers of families of
      monogeneans and digeneans in fishes. However, the nature of the families differ
      profoundly. Richness in higher taxa (families) in the Digenea is explicable in
      terms of processes that appear to have been unimportant in the Monogenea. Readily
      identifiable sources of diversity in the Digenea are: recolonisation of fishes by
      taxa that arose in association with tetrapods; adoption of new sites within
      hosts; adoption of new diets and feeding mechanisms; adaptations relating to the
      exploitation of ecologically similar groups of fishes and second intermediate
      hosts; and adaptations relating to the exploitation of phylogenetic lineages of
      molluscs. In contrast, most higher- level monogenean diversity (other than that
      associated with the subclasses) relates principally to morphological
      specialisation for attachment by the haptor.

PMID- 11835973
TI  - Fixed behaviours and migration in parasitic flatworms.
AB  - This paper considers how fixed behaviours may play a role in post-larval
      migrations of Entobdella soleae. A general argument is that a shift away from the
      paradigm of orientation is required to elucidate the mechanisms that parasites
      use to navigate on the surface of their hosts. Some migrations may rely on fixed
      behaviours (genetically programmed stereotyped behaviours) that often evolve
      under predictable environmental conditions with reliable signals. In turbulent
      and stochastic free-living environments, homeostatic hosts present very
      predictable topological substrates and physico-chemical characteristics to their
      parasites. Over the course of evolution on these predictable host substrates,
      adaptive behaviours in the parasites can become fixed. Examples of endoparasite
      migration behaviour, particularly that of the common liver fluke, Fasciola
      hepatica, will be used to develop an approach based on the perceptual worlds of
      migrating parasites. An important conclusion is that multi-disciplinary
      approaches, firmly rooted in an understanding of each parasite's natural history,
      are requisite to successful interpretation of migration behaviours on the host.

PMID- 11835974
TI  - Diversity and biogeographical relationships of the Australian cestode fauna.
AB  - The Australian cestode fauna remains poorly documented with a total of 342
      species recorded to date. The best-studied host groups are the elasmobranchs and
      the marsupials, but even in these groups, only 32 and 25% of known host species,
      respectively, have been examined for parasites. Overall, cestodes have been
      reported from only 5% of the known vertebrate species. Representatives of
      virtually all cestode orders and most of the cyclophyllidean families have been
      recorded from Australia. In spite of these deficiencies, some biogeographical
      patterns are discernible. In the elasmobranchs, a significant proportion of the
      known cestodes is endemic while other associations exist with eastern Pacific and
      Indo-west Pacific faunas. Also identifiable is a group of cosmopolitan species.
      The nematotaeniids of amphibians suggest Gondwanan affiliations, while the known
      proteocephalideans, parasitic in reptiles and amphibians, may represent an Asian
      invasion. Associations of the avian cestodes represent an unexplored but
      potentially rewarding avenue of biogeographical study. The cestodes of mammals
      include families with a Gondwanan distribution (Linstowiidae, Hymenolepididae) as
      well as those (Anoplocephalidae) with an apparent origin in southeast Asia. In
      addition, a number of genera of cyclophyllidean cestodes (Anoplotaenia,
      Dasyurotaenia) occurring in marsupials represent biogeographical challenges, not
      being accommodated within any of the known cestode families. The Australian
      cestode fauna therefore provides potentially outstanding opportunities for
      studies of the biogeographical relationships of a number of cestode groups.

PMID- 11835975
TI  - Host factors limiting monogenean infections: a case study.
AB  - Comprehensive field data on polystomatid monogeneans record low prevalence and
      intensity of infection and suggest that worm burdens in this group are strongly
      regulated: thus, in the majority of Polystoma species infecting anuran amphibians
      mean abundance is typically less than one parasite/host. There is circumstantial
      evidence that the dominant control is attributable to host factors which over
      ride variations in transmission success. This review provides a brief summary of
      information on Pseudodiplorchis americanus, a parasite of the desert toad,
      Scaphiopus couchii, and then focuses in detail on the spectrum of factors
      regulating infrapopulations of Protopolystoma xenopodis, a parasite of the
      aquatic Xenopus laevis. Infection levels of adult worms and their contribution to
      transmission are regulated by external environmental factors (especially
      temperature), by host factors (including behaviour and population density), and
      by a range of parasite factors including intra- and inter-specific competitive
      interactions and variations in intrinsic characters, especially survivorship and
      reproductive output. In addition to these factors whose primary effect is to
      modulate transmission rates, there is a major attrition in parasite numbers
      between invasion and maturity (3 months post-infection). Long-term laboratory
      experiments on the Xenopus laevis/Protopolystoma xenopodis interaction
      demonstrate a powerful acquired immune response. Primary infection is
      characterised by a high prevalence of established adult worms but the success of
      subsequent challenge infection is greatly reduced, leading to low prevalence and
      extended pre-patent period. In the small proportion of hosts supporting a second
      infection of adult parasites, surviving burdens are small (one to two worms/host)
      and show reduced egg production. These results provide an explanation for the low
      burdens encountered in field studies: a majority of adult X. laevis in natural
      populations are likely to exhibit strong, relatively long-term, post-infection
      immunity after the loss of a previous infection.

PMID- 11835976
TI  - Entobdella soleae--pointers to the future.
AB  - The biology of the monogenean skin parasite Entobdella soleae and its
      relationship with its host, the common sole (Solea solea), are probably better
      known than those of any other monogeneans. The author describes his early
      involvement with this parasite and the special features of parasite and host that
      make this relationship so suitable for parasitological studies. Aspects of the
      biology of E. soleae that have been investigated are briefly mentioned, but most
      of the paper is concerned with areas of the parasite's biology that remain a
      challenge to determine. Unresolved areas are as follows: (1) the identity of the
      factor (or factors) in host skin mucus that stimulates hatching of the parasite's
      eggs; (2) whether or not the larvae of the parasite are attracted to their host;
      (3) the nature of factors controlling the contrasting behaviour of adult
      parasites on the upper and lower surfaces of the host; (4) how nutrients are
      supplied to the remote regions of the haptor; (5) whether the host has any
      control via its immune system over parasite invasion success and survival; (6)
      how the parasite copes with the migratory habits of some sole populations,
      assuming that such populations are infested with the parasite. The intimacy of
      this parasite/host relationship is its most remarkable feature, the reflection of
      which, not surprisingly, is the greatly restricted host range of the parasite. E.
      soleae has been reported from only three host species, all highly specialised
      bottom-dwelling members of Solea. It is all the more surprising that relatives of
      E. soleae, such as Neobenedenia melleni, retain the ability to parasitise an
      enormous range of hosts. How this versatility is achieved remains to be seen.

PMID- 11835977
TI  - Impacts of diclidophorid monogenean infections on fisheries in Japan.
AB  - Many monogeneans are pathogenic to economically important fish in Japan. However
      no other monogenean is comparable with the diclidophorids, Heterobothrium
      okamotoi and Neoheterobothrium hirame, on the scale of impacts they inflict on
      Japanese fisheries. The shared importance of the two monogenean infections lies
      in their pathogenicity, fecundity and tolerance to chemical treatment.
      Heterobothrium okamotoi infects the gills and wall of the branchial cavity of the
      tiger puffer, Takifugu rubripes (Tetraodontidae), which is widely cultured in
      western Japan. The main presenting signs of infected fish are anaemia and
      extensive necrosis caused by adult worms. This monogenean deposits long strings
      of eggs, which reach lengths of almost 3 m. Egg entanglement with the mesh of
      culture nets increases the chance of hatched larvae encountering susceptible
      fish. The oncomiracidium maintains infectivity for up to 4 days after hatching.
      Hydrogen peroxide is the only commercially available chemical able to control the
      infection, but can only kill immature worms on the gills. Neoheterobothrium
      hirame infects the gills and wall of the buccal cavity of the Japanese flounder,
      Paralichthys olivaceus (Paralichthyidae). Since the first known occurrence of
      this monogenean in 1993, the species has been recorded from almost all areas
      where the host is distributed. Neoheterobothrium hirame has the potential to
      produce 781 eggs per day at 20 degree C. In the western Sea of Japan, wild young
      of-the-year flounder became infected in early summer, followed by a sharp
      increase in prevalence in late summer. By late summer, juvenile flounder have
      nearly disappeared from the area, strongly suggesting that N. hirame is
      responsible for mortality of young fish. This is in good agreement with the
      recent decline in the local flounder population. Neoheterobothrium hirame has
      also been considered the causative agent of anaemia among wild Japanese flounder
      since the late 1990s.

PMID- 11835978
TI  - Attachment-inducing capacities of fish skin epithelial extracts on oncomiracidia
      of Benedenia seriolae (Monogenea: Capsalidae).
AB  - Attachment-inducing capacities of skin epithelial extracts of yellowtail,
      Japanese flounder and red sea bream on oncomiracidia of the monogenean Benedenia
      seriolae were examined. Clear differences were not detected in the capacity among
      the fish species, although B. seriolae infects only yellowtail and its congeners
      in Seriola. This suggests that either the capacity is not host specific or host
      specific attachment-inducing capacity cannot be detected by the assay method.
      Further, the attachment-inducing capacities were suppressed by wheat-germ lectin
      and concanavalin A in skin epithelial extracts of Japanese flounder and
      yellowtail, respectively. This suggests that some sugar-related chemical
      substances existing in fish epithelia induce the attachment of B. seriolae
      oncomiracidia.

PMID- 11835980
TI  - Tactile, acoustic and vestibular systems sum to elicit the startle reflex.
AB  - The startle reflex is elicited by intense tactile, acoustic or vestibular
      stimuli. Fast mechanoreceptors in each modality can respond to skin or head
      displacement. In each modality, stimulation of cranial nerves or primary sensory
      nuclei evokes startle-like responses. The most sensitive sites in rats are found
      in the ventral spinal trigeminal pathway, corresponding to inputs from the dorsal
      face. Cross-modal summation is stronger than intramodal temporal summation,
      suggesting that the convergence of acoustic, vestibular and tactile information
      is important for eliciting startle. This summation declines sharply if the cross
      modal stimuli are not synchronous. Head impact stimuli activate trigeminal,
      acoustic and vestibular systems together, suggesting that the startle response
      protects the body from impact stimuli. In each primary sensory nucleus, large,
      second-order neurons project to pontine reticular formation giant neurons
      critical for the acoustic startle reflex. In vestibular nucleus sites, startle
      like responses appear to be mediated mainly via the vestibulospinal tract, not
      the reticulospinal tract. Summation between vestibulospinal and reticulospinal
      pathways mediating startle is proposed to occur in the ventral spinal cord.

PMID- 11835981
TI  - A sexual arousability model involving steroid effects at the plasma membrane.
AB  - This review will discuss the status of research related to sexual arousability.
      It will also present a model for sexual arousability based on current knowledge
      of steroids effects at the membranes of cells. Steroids have multiple rapid
      actions that are suggested to result from actions at membrane-associated
      receptors. When stimulated by steroids these receptors alter G-protein coupling
      in a manner unique to this complex. Initial stimulation of the receptors by
      steroids alters the coupling pattern of G-proteins and of other binding sites
      associated with the complex. This change in G-protein coupling is a stable
      alteration and thus may serve as a long-term change in the system, which is a
      requirement of sexual arousability. Stimulation of this receptor system by a
      surge of oxytocin at ejaculation or orgasm then decouples the G-protein and
      reduces arousability. Sex hormone binding globulin may be an important ligand at
      this complex. This model suggests completely new relationships among steroids and
      their receptors that may complement or diverge from actions at known
      intracellular receptors.

PMID- 11835982
TI  - Orgasm-induced prolactin secretion: feedback control of sexual drive?
AB  - Recent studies from our laboratory have investigated the hormonal response to
      various forms of sexual stimulation, including film, masturbation, and coitus in
      both men and women. This series of studies clearly demonstrated that plasma
      prolactin (PRL) concentrations are substantially increased for over 1h following
      orgasm (masturbation and coitus conditions) in both men and women, but unchanged
      following sexual arousal without orgasm. Here we discuss evidence suggesting that
      the PRL response to orgasm may play an important role in the control of acute
      sexual arousal following orgasm. Supporting this position, chronic elevations of
      PRL (hyperprolactinemia) produce pronounced reductions in animal sexual activity,
      and significant reduction of libido and gonadal function in both men and women.
      These data suggest that PRL may represent a peripheral regulatory factor for
      reproductive function, and/or a feedback mechanism that signals CNS centres
      controlling sexual arousal and behaviour. Thus, we propose a theoretical model of
      the role of PRL as a neuroendocrine reproductive reflex.

PMID- 11835983
TI  - Thyroid hormones, brain function and cognition: a brief review.
AB  - In addition to their role in cellular metabolic activity, thyroid hormones (THs),
      also regulate neural development; the central nervous system is particularly
      dependent on TH for normal maturation and function. Specifically, there appears
      to be extensive inter-reliance between TH and acetylcholine (Ach), nerve growth
      factor and hippocampal function. These associations led us to investigate the
      possible effects of thyroxine (L-T4) on performance of a spatial learning task,
      where cholinergic activity and hippocampal function are known to be important.
      Groups of rats (n=20) received saline (controls) or L-T4 at 2.5 or 5mg/kg daily
      for 4 days as a sub-chronic treatment, or 0, 5 or 10mg/kg doses administered
      every third day for 28 days prior to testing as a chronic regimen. Rats were
      assessed in a water maze for their ability to find a submerged or visible
      platform. Forty minutes prior to water maze testing, half the animals in each
      group received 1mg/kg scopolamine to elicit a cognitive deficit. Following
      testing, rats were decapitated, blood samples taken, and the frontal cortex and
      hippocampus were dissected out for acetylcholinesterase (AChE) assay. The results
      showed that L-T4 treatment, administered both sub-chronically and chronically,
      significantly enhanced the ability of rats to learn a spatial memory task,
      compared with controls. Moreover, both short-term and long-term L-T4 treatment
      reduced the cognitive-impairing effects of scopolamine. Improvements in
      performance were shown to occur alongside significantly increased cholinergic
      activity in frontal cortex and in the hippocampus of treated animals. These
      findings demonstrate an augmentative effect of L-T4 upon cognitive function,
      possibly mediated by an enhancement of cholinergic activity. The results support
      previous findings of a relationship between L-T4 and acetylcholine, and
      underscore possible mechanisms by which disorders of thyroid function may be
      associated with cognitive decline.

PMID- 11835984
TI  - Mechanisms and abuse liability of the anti-histamine dimenhydrinate.
AB  - The over-the-counter anti-emetic dimenhydrinate (DMH) (Gravol or Dramamine) has
      been reported to be abused for non-medicinal purposes. Street drug users abuse
      DMH for the acute effects of euphoric sensations and hallucinations, while
      psychiatric patients abuse DMH for its anxiolytic or anti-cholinergic effects.
      DMH is an H(1) histamine receptor antagonist, but it interacts either directly or
      indirectly with other neurotransimitter systems, including those using
      acetylcholine, serotonin, norepinephrine, dopamine, opioids or adenosine. Animal
      behavioural studies, such as self-administration, conditioned place preference,
      drug discrimination, and modulation of operant responding, show that anti
      histamines have abuse potential. Further support comes from reports of acute and
      chronic abuse of DMH by humans. Collectively, results confirm the abuse liability
      of DMH.

PMID- 11835985
TI  - Including 'learned sexuality' in the organization of sexual behavior.
AB  - Learning plays numerous important roles in sexual development. Yet, the possible
      impacts on sexuality, of learning from experience, are rarely included in
      discussions of the organization of behavioral sex differences and the
      differentiation of psychosexual function. This article reviews the empirical
      evidence for 'learned sexuality' with a goal of reintroducing the topic of
      nurture into discussions of the ontogenetic processes that lead to sexual
      reproduction in nature. Evolutionarily relevant examples of sexual learning are
      broadly represented in the animal kingdom, and can occur relatively early in
      development, leading to lasting changes in behaviors that might otherwise appear
      to be instinctive, or in other cases, maladaptive. The lasting effects of social
      and sexual experiences across the lifespan provide an essential link between
      steroid-mediated events occurring during development, behavioral plasticity, and
      changes in motivational states in adulthood.

PMID- 11835986
TI  - The neurobehavioural consequences of petrol (gasoline) sniffing.
AB  - This review will introduce petrol (gasoline) sniffing as a specific form of
      substance abuse. Petrol sniffing is associated with dysfunctions that range in
      severity from subtle cognitive impairment to encephalopathy and death, and these
      are discussed with respect to their specific neurological and cognitive bases.
      Morbidity and mortality rates will also be presented that suggest severe central
      nervous system damage occurs as a result of petrol sniffing. The
      neuropharmacological actions of tetraethyl lead and volatile hydrocarbons, the
      components within petrol, and their contributions to the effects of sniffing
      petrol are investigated. Reports of human occupational or recreational exposure
      to either lead additives or volatile hydrocarbons (i.e. inhalants) have provided
      evidence of the neurological and cognitive effects that may also occur with
      petrol sniffing. Petrol sniffing causes a progressive decline of cognitive
      function that eventually leads to permanent neurological changes.

PMID- 11835987
TI  - The neurobiological basis of spontaneous alternation.
AB  - When placed in a T-maze, rats or mice possess a strong tendency of alternating
      arm choices on successive trials. The exploration of novel environmental stimuli
      is dependent on the integrity of limbic and non-limbic pathways, including the
      basal forebrain, the hippocampus, the thalamus, the prefrontal cortex, and the
      dorsal striatum, as well as the vestibular system and cerebellum. Neurochemical
      pathways using acetylcholine, gamma-amino-butyric acid, and dopamine in the
      septum and hippocampus have been implicated in the exploration of novel maze
      arms. In addition to the delineation of interactions between neurotransmitters,
      the spontaneous alternation test is sensitive to the consequences of normal and
      pathological aging.

PMID- 11835988
TI  - Fragment of human beta-fibrinogen induces a behavioral effect on mouse forced
      swimming.
AB  - We detected a peptide having a behavioral activity on mouse forced swimming from
      sera of healthy volunteers without affective and psychotic diseases. The amino
      acid sequence was GVNDNEEGF, which was found in the sequence of human beta
      fibrinogen. The synthesized peptide also showed the behavioral activity dose
      dependently, but human fibrinopeptide B (QGVDNEEGFFSAR) did not. The activity was
      decreased by dopamine 1 antagonist SCH-23390, but not by dopamine 2 antagonist
      sulpiride. These findings strongly suggest that metabolism of human beta
      fibrinogen induces the fragment affecting the mouse behavior via the dopamine1
      neuronal activity.

PMID- 11835989
TI  - Antibacterial activities and conformations of bovine beta-defensin BNBD-12 and
      analogs:structural and disulfide bridge requirements for activity.
AB  - Structure and biological activities of synthetic peptides corresponding to bovine
      neutrophil beta-defensin BNBD-12, GPLSC(1)GRNGGVC(2)IPIRC(3) PVPMRQIGTC(4)
      FGRPVKC(5) C(6)RSW with disulfide connectivities C(1)-C(5), C(2)-C(4) and C(3)
      C(6) and its variants with one, two and three disulfide bridges have been
      investigated. Selective protection of cysteine thiols was necessary in the four
      and six cysteine containing peptides for the formation of disulfide
      connectivities as observed in BNBD-12. Circular dichroism (CD) spectra indicate
      that in aqueous medium, only a small fraction of molecules populate turn-like
      conformations. In the presence of micelles and lipid vesicles, the single, two
      and three disulfide containing peptides adopt beta-hairpin or beta-sheet
      structures. Antibacterial activity was observed for all the peptides,
      irrespective of the number of disulfide bridges or how they were connected. Our
      results suggest that a rigid beta-sheet structure or the presence of three
      disulfide bridges does not appear to be stringent requirements for antibacterial
      activity in beta-defensins.

PMID- 11835990
TI  - Antimicrobial peptides with atypical structural features from the skin of the
      Japanese brown frog Rana japonica.
AB  - Japonicin-1 (FFPIGVFCKIFKTC) and japonicin-2 (FGLPMLSILPKALCILLKRKC), two
      peptides with differential growth-inhibitory activity against the Gram-negative
      bacterium, Escherichia coli and the Gram-positive bacterium Staphylococcus
      aureus, were isolated from an extract of the skin of the Japanese brown frog Rana
      japonica. Both peptides show little amino acid sequence similarity to previously
      characterized antimicrobial peptides isolated from the skins of Ranid frogs.
      Circular dichroism studies, however, demonstrate that japonicin-2 adopts an alpha
      helical conformation in 50% trifluoroethanol in common with many other cationic
      antimicrobial peptides synthesized in amphibian skin. Peptides belonging to the
      brevinin-1, brevinin-2, and tigerinin families, previously identified in the
      skins of Asian Ranid frogs, were not detected but a temporin-related peptide
      (ILPLVGNLLNDLL.NH(2); temporin-1Ja), that atypically bears no net positive
      charge, was isolated from the extract. The minimum inhibitory concentrations
      (MICs) of the peptides against E. coli were japonicin-1, 30 microM; japonicin-2,
      12 microM; and temporin-1Ja > 100 microM. The MICs against S. aureus were
      japonicin-1, > 100 microM; japonicin-2, 20 microM; and temporin-1Ja, > 100
      microM.

PMID- 11835991
TI  - Antimicrobial peptides from skin secretions of Chinese red belly toad Bombina
      maxima.
AB  - Two groups of antimicrobial peptides have been isolated from skin secretions of
      Bombina maxima. Peptides in the first group, named maximins 1, 2, 3, 4 and 5, are
      structurally related to bombinin-like peptides (BLPs). Unlike BLPs, sequence
      variations in maximins occurred all through the molecules. In addition to the
      potent antimicrobial activity, cytotoxicity against tumor cells and spermicidal
      action of maximins, maximin 3 possessed a significant anti-HIV activity. Maximins
      1 and 3 were toxic to mice with LD(50) values of 8.2 and 4.3 mg/kg, respectively.
      Peptides in the second group, termed maximins H1, H2, H3 and H4, are homologous
      with bombinin H peptides. cDNA sequences revealed that one maximin peptide plus
      one maximin H peptide derived from a common larger protein.

PMID- 11835992
TI  - A novel proline rich bombesin-related peptide (PR-bombesin) from toad Bombina
      maxima.
AB  - A novel bombesin-related peptide was isolated from skin secretions of Chinese red
      belly toad Bombina maxima. Its primary structure was established as pGlu-Lys-Lys
      Pro-Pro-Arg-Pro-Pro-Gln-Trp-Ala-Val-Gly-His-Phe-Met-NH(2.) The amino-terminal (N
      terminal) 8-residue segment comprising four prolines and three basic residues is
      extensively different from bombesins from other Bombina species. The peptide was
      thus named proline rich bombesin (PR-bombesin). PR-bombesin was found to elicit
      concentration-dependent contractile effects in the rat stomach strip, with both
      increased potency and intrinsic activity as compared with those of
      [Leu(13)]bombesin. Analysis of different bombesin cDNA structures revealed that
      an 8 to 14- nucleotide fragment replacement in the peptide coding region
      (TGGGGAAT in the cDNAs of multiple bombesin forms from Bombina orientalis and
      CACCCCGGCCACCC in the cDNA of PR-bombesin) resulted in an unusual Pro-Pro-Arg-Pro
      Pro motif in the N-terminal part of PR-bombesin.

PMID- 11835993
TI  - Cladistic analysis of anuran POMC sequences.
AB  - Procedures for performing cladistic analyses can provide powerful tools for
      understanding the evolution of neuropeptide and polypeptide hormone coding genes.
      These analyses can be done on either amino acid data sets or nucleotide data sets
      and can utilize several different algorithms that are dependent on distinct sets
      of operating assumptions and constraints. In some cases, the results of these
      analyses can be used to gauge phylogenetic relationships between taxa. Selecting
      the proper cladistic analysis strategy is dependent on the taxonomic level of
      analysis and the rate of evolution within the orthologous genes being evaluated.
      For example, previous studies have shown that the amino acid sequence of
      proopiomelanocortin (POMC), the common precursor for the melanocortins and beta
      endorphin, can be used to resolve phylogenetic relationships at the class and
      order level. This study tested the hypothesis that POMC sequences could be used
      to resolve phylogenetic relationships at the family taxonomic level. Cladistic
      analyses were performed on amphibian POMC sequences characterized from the marine
      toad, Bufo marinus (family Bufonidae; this study), the spadefoot toad, Spea
      multiplicatus (family Pelobatidae), the African clawed frog, Xenopus laevis
      (family Pipidae) and the laughing frog, Rana ridibunda (family Ranidae). In these
      analyses the sequence of Australian lungfish POMC was used as the outgroup. The
      analyses were done at the amino acid level using the maximum parsimony algorithm
      and at the nucleotide level using the maximum likelihood algorithm. For the
      anuran POMC genes, analysis at the nucleotide level using the maximum likelihood
      algorithm generated a cladogram with higher bootstrap values than the maximum
      parsimony analysis of the POMC amino acid data set. For anuran POMC sequences,
      analysis of nucleotide sequences using the maximum likelihood algorithm would
      appear to be the preferred strategy for resolving phylogenetic relationships at
      the family taxonomic level.

PMID- 11835994
TI  - Design, synthesis and pharmacological characterization of new highly selective
      CRF(2) antagonists: development of 123I-K31440 as a potential SPECT ligand.
AB  - Novel analogs of antisauvagine-30 (aSvg-30), a specific antagonist for
      corticotropin-releasing factor (CRF) receptor, type 2 (CRF(2)), have been
      synthesized and characterized in vitro and in vivo. The N-terminal amino acid D
      phenylalanine in aSvg-30 was replaced by a D-tyrosine residue for specific
      radioactive labeling with 123I. Additionally, Met(17) of aSvg-30 was substituted
      by norleucine and the N-terminus of the peptide was acetylated to increase in
      vivo metabolic stability. The aSvg-30 analogs were tested for their ability to
      displace [125I-Tyr(0)]Svg in binding experiments and to inhibit Svg-stimulated
      adenylate cyclase activity in human embryonic kidney (HEK) 293 cells, permanently
      transfected with cDNA coding for the human CRF(1) (hCRF(1)), hCRF(2alpha) and
      hCRF(2beta) receptor. Ac-[D-Tyr(11), His(12), Nle(17)Svg(11-40), named K31440,
      showed high specific binding to hCRF(2alpha) (K(i) = 1.48 +/- 0.34 nM) and
      hCRF(2beta) (K(i) = 2.05 +/- 0.61 nM) but not the hCRF(1) receptor (K(i) = 288 +/
      13 nM) and decreased Svg-stimulated cAMP activity in hCRF(2)-expressing cells in
      a similar fashion as aSvg-30. In biodistribution studies specific uptake of 123I
      K31440 was detected after 1 h in small intestine of BALB/c nude mice. These data
      demonstrate that 123I-K31440 may serve as a useful tool to detect native CRF(2)
      receptors and elucidate their role in gastrointestinal disorders and diseases
      such as irritable bowel syndrome or cancer.

PMID- 11835995
TI  - Peptidase activities in human semen.
AB  - Enkephalins are one of the opioids present in human semen and to date their
      function in this tissue remains unknown. The present work studies enkephalin
      degrading enzyme activities, puromycin-sensitive alanyl aminopeptidase (AAP-S),
      puromycin-insensitive alanyl aminopeptidase N (Ap N) and neprilysin (NEP) in
      human seminal fractions. AAP-S activity was not detected in any fractions,
      whereas Ap N appeared in soluble and particulate sperm fractions in seminal fluid
      and in prostasome fraction. With regard to NEP activity, this was exclusively
      located in prostasome membranes. The high activity values observed in the
      prostasome fraction suggested that these peptidases and their substrates could be
      involved in seminal physiology.

PMID- 11835996
TI  - High airway-to-blood transport of an opioid tetrapeptide in the isolated rat lung
      after aerosol delivery.
AB  - The airway-to-blood absorption of the mu-selective opioid tetrapeptide agonist
      Tyr-D-Arg-Phe-Phe-NH(2) (MW 631) was investigated in the isolated, perfused, and
      ventilated rat lung model. The lung metabolism of the peptide was compared after
      airway and vascular delivery. The concentrations of the parent tetrapeptide and
      five of its metabolites in the perfusate and in bronchoalveolar lavage fluid were
      analyzed by LC-MS. The metabolism of the peptide was higher after delivery to the
      airways compared to vascular delivery. However, the tetrapeptide was highly
      transported from the air-to-blood side to an extent of 47.8 +/- 10.7% in 2 h. In
      conclusion, the results prompt investigations of the pulmonary route as a
      successful alternative to parenteral delivery for this tetrapeptide.

PMID- 11835997
TI  - Regional differences in bioavailability of an opioid tetrapeptide in vivo in rats
      after administration to the respiratory tract.
AB  - TArPP (Tyr-D-Arg-Phe-Phe-NH(2)), 1-10 micromol/kg, was administered to
      anesthetized rats by nasal microinfusion, intratracheal microinfusion,
      intratracheal nebulization, aerosol inhalation, and i.v. bolus and infusion.
      Plasma concentrations of TArPP and its deamidated metabolite were determined by
      LC-MS-MS. Regional differences in bioavailability (F), first-pass metabolism, and
      absorption rate were found for TArPP after delivery to the respiratory tract.
      Absorption was rapid after both pulmonary and nasal administration (t(max)
      approximately 10-20 min). After nasal microinfusion, F was 52 +/- 9%. For all the
      pulmonary groups, F was higher (72-114%). First-pass metabolism of TArPP was
      lower in the lung than in the nasal cavity. It is evident that the pulmonary
      route is attractive for successful systemic delivery of small, hydrophilic and
      enzymatic susceptible peptides.

PMID- 11835999
TI  - Nociceptin, OP4 receptor ligand in different models of experimental epilepsy.
AB  - The anticonvulsive activity of nociceptin, endogenous OP4 receptors agonist was
      investigated in pentylenetetrazole (PTZ), N-methyl D-aspartic acid (NMDA),
      bicucculine (BCC) and electrically evoked seizure models of experimental
      epilepsy. Nociceptin, at the dose of 10 nmol, suppressed the clonic seizures
      induced by PTZ, NMDA and BCC. [Phe1(psi)(CH2-NH)Gly2]nociceptin-(1-13)-NH2 which
      has been proposed to be selective antagonist OP4 receptors, did not prevent the
      action of nociceptin. The effect of [Phe1(psi)(CH2-NH)Gly2]nociceptin-(1-13)-NH2
      on seizures induced by PTZ, NMDA and BCC was very similar to that of nociceptin.
      These data support the hypothesis that it possesses agonistic properties.
      Naloxone did not reverse the anticonvulsive action of nociceptin as well as
      [Phe1(psi)(CH2-NH)Gly2]nociceptin-(1-13)-NH2 which excludes the participation of
      opioid receptor in this action. On the other hand in the electroconvulsive model
      of generalized seizures, nociceptin as well as [Phe1(psi)(CH2-NH)Gly2]nociceptin
      (1-13)-NH2 influenced neither the electroconvulsive threshold nor the maximal
      electroshock test. The data suggest that nociceptin and [Phe1(psi)(CH2
      NH)Gly2]nociceptin-(1-13)-NH2 can exert anticonvulsive action. These properties
      depend on OP4 but not opioid receptors activation.

PMID- 11835998
TI  - Dansyl-PQRamide, a possible neuropeptide FF receptor antagonist, induces
      conditioned place preference.
AB  - Neuropeptide FF (NPFF) is an endogenous anti-opioid peptide. NPFF could
      potentiate the naloxone-precipitated morphine withdrawal syndromes in morphine
      dependent rats, indicating the possible involvement of the endogenous NPFF system
      in opioid analgesia and dependence. The present study was performed to examine
      the effects of dansyl-PQRamide (dns-PQRa), a putative NPFF antagonist, on
      conditioned place preference (CPP), in addition, its interaction with the opioid
      system. Two CPP experiments were conducted. First, rats were treated with dns
      PQRa (4-13 mg/kg, i.p.) and paired with the non-preferred compartment while the
      vehicle was paired with the preferred compartment. Second, similar to experiment
      1 except naloxone (1 mg/kg, i.p.) was given 10 min prior to each dns-PQRa
      administration. The post-drug place preference was examined after 4 alternative
      pairings. Another group of animals after repetitive dns-PQRa treatments were
      analyzed for levels of neurotransmitters in discrete brain areas. Dns-PQRa (4-13
      mg/kg, i.p.) induced a significant dose-dependent CPP. The dns-PQRa-induced CPP
      was completely blocked by pretreatment with 1 mg/kg i.p. naloxone, while naloxone
      alone did not induce any place aversion. The chronic dns-PQRa-treated (13 mg/kg,
      i.p., b.i.d.) rats caused a significant increase in 3,4-dihydroxyphenylacetic
      acid and 5-hydroxyindoleacetic acid in the olfactory tubercle compared to the
      vehicle-treated controls. There was also an increase in the turnover of serotonin
      in the olfactory tubercle, nucleus accumbens and medial prefrontal cortex. These
      results suggest that blockade of the NPFF system produces rewarding, possibly via
      an inhibition of the anti-opioid action of NPFF. These results also reveal a
      close relationship between NPFF, drug rewarding and the dopaminergic and
      serotoninergic neurons in the mesolimbic system.

PMID- 11836000
TI  - Calcitonin gene-related peptide-receptor component protein expression in the
      uterine cervix, lumbosacral spinal cord, and dorsal root ganglia.
AB  - The neuropeptide calcitonin gene-related peptide (CGRP) may play a role in
      neurogenic inflammation, tissue remodeling of the uterine cervix, promoting
      vasodilation, parturition, and processing of sensory information in the spinal
      cord. CGRP-immunoreactive nerves of the cervix and spinal cord have been studied
      but cellular identification of the CGRP receptor has received little attention.
      CGRP-receptor component protein (CGRP-RCP) is a small protein associated with the
      CGRP receptor; thus, immunostaining for the CGRP-RCP can be used to identify
      sites of the CGRP receptor. We determined sites of CGRP-RCP immunoreactivity
      relative to the presence of CGRP-ir nerve fibers in the female rat uterine
      cervix, spinal cord, and dorsal root ganglia. CGRP-RCP immunoreactivity was
      expressed in the dorsal horn of the spinal cord, venules of the uterine cervix,
      and perikarya of sensory neurons in dorsal root ganglia. CGRP-immunoreactive
      fibers were adjacent to CGRP-RCP-immunoreactive vessels in the cervix and among
      CGRP-RCP-immunoreactive structures in the dorsal horn of the spinal cord. This
      suggests CGRP-RCP is associated with structures innervated by CGRP nerves and
      these interactions may be changed in tissues in response to an appropriate
      stimulus.

PMID- 11836001
TI  - Distribution of urocortin in the rat's gastrointestinal tract and its
      colocalization with tyrosine hydroxylase.
AB  - Urocortin (Ucn), a newly identified member of the corticotropin-releasing factor
      (CRF) family, is not only expressed in the brain, but also abundantly present in
      the peripheral tissues, especially in the gastrointestinal tract (GI) as
      determined by radioimmuoassay. In order to determine the precise localization of
      urocorin in the GI, we mapped the distribution of urocortin-like immunoreactivity
      (ir) in the GI of the rat using an immunofluorescence histochemical technique.
      Ucn, both in the brain and the peripheral tissues, is involved in the regulatory
      control of host-defense mechanism during stress. In order to study the possible
      involvement of the sympathetic system in the expression of GI urocortin in
      response to stress, we examined the effect of chemical sympathectomy on urocortin
      ir and its colocalization with tyrosine hydroxylase (TH). UCn was expressed in
      all parietal cells of the stomach, myenteric and submucosal plexuses as well as
      in cells in Lieberkuhn crypts of the small and large intestine. Most of the acid
      secreting parietal cells contained both Ucn and TH. Chemical sympathectomy did
      not affect Ucn immunoreactivity of parietal cells.

PMID- 11836002
TI  - Interaction of xenin with the neurotensin receptor of guinea pig enteral smooth
      muscles.
AB  - Xenin, a 25 aminoacid peptide, interacts with the neurotensin receptor subtype 1
      of intestinal muscles of the guinea pig. Replacement of the C-terminal Lys -Arg
      peptide bond in xenin 6 by a reduced pseudo-peptide bond augmented binding
      affinity to isolated jejunal and colonic muscle membranes by factors of 7.7 and
      21.0 respectively; the potency to contract the jejunum and to relax the colon was
      increased by factors of 3.2 and 1.3. The C-terminus Trp-Ile-Leu (WIL) of xenin,
      in contrast to the C-terminus Tyr-Ile-Leu (YIL) of neurotensin, bound
      competitively to the muscle membranes. WIL blocked the contractile action of
      xenin in the jejunum and was synergistic with the relaxing action in the colon.
      The Lys -Arg motif and Trp in the C-terminus of xenin are essential structures in
      the action of xenin on the enteral smooth muscle receptors.

PMID- 11836003
TI  - Ghrelin-producing cells exist as two types of cells, closed- and opened-type
      cells, in the rat gastrointestinal tract.
AB  - Ghrelin was recently isolated from the rat stomach as an endogenous ligand for
      the growth-hormone secretagogue receptor (GHS-R) and is known to exist in the
      gastrointestinal tract and hypothalamus. In this study, we investigated in detail
      the distribution and morphologic characteristics of ghrelin-containing cells
      (ghrelin cells) in the gastrointestinal tract by immunohistochemistry and in situ
      hybridization. Ghrelin cells were found to be localized in the mucous membrane of
      the stomach, duodenum, ileum, cecum and colon but not in myenteric plexus, and
      they can be classified into open- and closed-type cells. The greatest number of
      ghrelin cells was found in the stomach, and it was found that the number of the
      opened-type cells gradually increased in the direction from stomach to the lower
      gastrointestinal tract. These results suggest that the two types of ghrelin cells
      may be distinctly regulated and play different physiological roles in various
      regions of the gastrointestinal tract.

PMID- 11836004
TI  - Comparative study of enterostatin sequence in five rat strains and enterostatin
      binding proteins in rat and chicken serum.
AB  - Enterostatin, a pentapeptide derived from the precursor protein procolipase has
      been shown to inhibit dietary fat intake and to reduce body fat after chronic
      administration in rats. We repeat that the enterostatin amino acid sequence from
      the genomic DNA of 5 different rat strains is APGPR. 125I-APGPR bound to three
      proteins (300, 205 and 60 kDa) in rat serum and one 60 kDa protein in chicken
      serum. These serum binding proteins were also eluted by APGPR affinity
      chromatography. Western blot analysis of serum protein identified enterostatin
      like immunoreactivity associated with the same molecular weight bands. Our
      results demonstrate the enterostatin sequence in rat is APGPR and suggest the
      presence of enterostatin binding proteins in rat and chicken serum.

PMID- 11836005
TI  - Discrimination of galanin receptor subtypes in RINm5F cells by structurally
      different galanin radioligands.
AB  - Galanin (GAL) is a biologically active peptide that is involved in a variety of
      physiological functions. The purpose of this study was to evaluate whether
      porcine and rat galanin radioligands could be used as probes to discriminate GAL
      receptors (GALR) subtypes using a cell line, RINm5F, that express multiple GALR
      subtypes. Data from parallel equilibrium binding experiments using the same
      RINm5F membrane homogenates reveal that [125I]pGAL labels 20% more GALRs with a 2
      fold lower affinity than those values identified when using [125I]rGAL.
      Competition studies using various GAL peptides showed different rank order of
      potencies depending on the radioligand used. Preincubation of RINm5F membranes
      with GppNHp, a non-hydrolizable GTP analog, prior to radioligand labeling
      suggests that a portion of GALRs is precoupled to G proteins. In addition,
      receptors labeled by [125I]rGAL appear more sensitive to GppNHp-induced
      uncoupling of G proteins than those labeled by [125I]pGAL. In conclusion, our
      data suggest that pGAL and rGAL radioligands define different pharmacological
      profiles of GALRs, and hence, these ligands can be used as pharmacological tools
      to discriminate GALR subtypes. Additionally, our data suggests that GALRs exist
      in a precoupled state with their respective G-proteins prior to interaction with
      the agonist.

PMID- 11836006
TI  - Effect of a regulatory mutation on the rat atrial natriuretic peptide gene
      transcription.
AB  - To investigate the functional relevance of a regulatory mutation affecting the
      enhancer element PEA2 of the rat ANP gene we transfected rat cardiomyocytes and
      aortic endothelial cells with either the mutant or the wild-type ANP promoter
      construct (-683 +54) and performed CAT assays both at baseline and in response to
      Phenylephrine and Angiotensin II. In the myocardial cells we also determined the
      DNA/nuclear protein interaction through electrophoretic mobility shift assay.
      These studies showed a significantly lower degree of ANP transcription in the
      presence of the mutant PEA2 site, thus demonstrating its functional significance
      and the biological relevance of ANP gene structural alterations.

PMID- 11836007
TI  - Mechanisms transducing the aldosterone secretagogue signal of endothelins in the
      human adrenal cortex.
AB  - Evidence has been provided that the 21-amino acid hypertensive peptide endothelin
      (ET)-1 exerts a potent secretagogue effect on human adrenocortical zona
      glomerulosa (ZG), acting through two receptor subtypes, called ET(A) and ET(B),
      the signaling mechanism(s) of which has (have) not yet been investigated.
      Collagenase dispersed human ZG cells were obtained from normal adrenals of
      patients undergoing nephrectomy/adrenalectomy for renal cancer. The selective
      ET(A)- and ET(B)-receptor activation was obtained by exposing dispersed cells to
      ET-1 plus the ET(B)-receptor antagonist BQ-788 and to the ET(B)-receptor agonist
      BQ-3020, respectively. The phospholipase (PL) C inhibitor U-73122 abolished ET(A)
      receptor-mediated secretory response, but only partially prevented the ET(B)
      receptor-mediated one. The phosphatidylinositol 3-kinase inhibitor wortmannin,
      the calmodulin inhibitor W-7 and the protein kinase (PK) C inhibitor calphostin-C
      significantly blunted the secretory responses ensuing from the activation of both
      receptor subtypes. When added together, calphostin-C and wortmannin or W-7
      abolished ET(A)-mediated secretory response, but only decreased ET(B)-mediated
      one. The ET(B) receptor-, but not the ET(A) receptor-mediated aldosterone
      response was partially reversed by the cyclooxygenase (COX) inhibitor
      indomethacin, which when added together with U-73122 abolished it. ET(A)-receptor
      activation raised inositol triphosphate (IP(3)) production from dispersed ZG
      cells, while ET(B)-receptor stimulation enhanced both IP(3) and prostaglandin
      E(2) production. Collectively, our findings indicate that ETs stimulate
      aldosterone secretion from human ZG cells, acting through ET(A) receptors
      exclusively coupled to PLC/PKC-dependent pathway and ET(B) receptors coupled to
      both PLC/PKC- and COX-dependent cascades.

PMID- 11836008
TI  - Preparation of an active recombinant peptide of crustacean androgenic gland
      hormone.
AB  - In crustaceans, male sexual characteristics are induced by a hormone referred to
      as androgenic gland hormone. We have recently cloned a candidate cDNA in the
      terrestrial isopod Armadillidium vulgare. In order to prove that this cDNA
      encodes the hormone, recombinant single-chain precursor molecules consisting of B
      chain, C peptide and A chain were produced using both baculovirus and bacterial
      expression systems. Neither recombinant precursors showed activity. Digestion of
      only the precursor carrying a glycan moiety with lysyl endopeptidase gave a
      heterodimeric peptide with hormonal activity by removing a part of C peptide.
      These results indicate that the cDNA encodes the hormone.

PMID- 11836010
TI  - Post-trial administration of vasopressin in humans does not enhance memory
      formation (vasopressin and memory consolidation).
AB  - Many animal studies show an enhancing effect of vasopressin (VP) on memory, but
      not all human studies could confirm this finding. This study examined the
      influence of post-learning administration of VP (40 IU, intranasally) on the
      consolidation of declarative memories in healthy humans during different
      intervals of sleep and waking. We could not find any effect of VP on memory
      consolidation, but EEG activity indicated a significant arousing influence of VP.
      Results suggest that if VP affects memory function it might do so primarily at
      the stage of encoding of the materials to be learned but it leaves unaffected
      processes of consolidation.

PMID- 11836009
TI  - A synthetic peptide with estrogen-like activity derived from a phage-display
      peptide library.
AB  - We describe a novel approach to develop peptides with estrogen like activity
      using a monoclonal antibody specific to estradiol (mAb E2-15) for the affinity
      selection of phage displayed peptides from a combinatorial peptide library. Based
      on the sequences of the selected phage, we synthesized a 15-mer linear peptide
      LPALDPTKRWFFETK which was derivatized to a 23 mer cyclic peptide
      CAELPALDPTKRWFFETKPPPPC. Both peptides displayed estrogen-like activity according
      to the following criteria:(i) in inhibiting the binding of [3H]estradiol to mAb
      E2-15 and to estrogen receptor (ER)alpha; (ii) in inducing transcriptional
      activity in MCF7 human breast cancer cells transfected with an estrogen receptor
      element luciferase construct and (iii) in causing an increase in creatine kinase
      specific activity in rat tissues in vivo. This approach can be employed to design
      peptide mimetic for other hormones as well.

PMID- 11836011
TI  - Identification of the cockroach neuropeptide Pea-CAH-II as a second adipokinetic
      hormone in the firebug Pyrrhocoris apterus.
AB  - A new member of the AKH/RPCH family was isolated from the corpora cardiaca of the
      firebug Pyrrhocoris apterus. It is the second adipokinetic peptide identified in
      this species. The peptide was characterized and its structure was deduced from
      the multiple MS(N) electrospray mass spectra as that of an octapeptide with the
      sequence pGlu-Leu-Thr-Phe-Thr-Pro-Asn-Trp-NH(2.) The peptide differs from the
      original P. apterus AKH (Pya-AKH) by one amino acid in position 3. Topical
      application and/or injection of the peptide induced lipid mobilization, but was
      inactive in mobilization of carbohydrates.

PMID- 11836012
TI  - Alzheimer's disease through the eye of a mouse. Acceptance lecture for the 2001
      Gayle A. Olson and Richard D. Olson prize.
AB  - There is now ample evidence that beta-amyloid proteins decrease memory. The SAMP8
      mouse (P8) develops an early decline in the ability to learn and to retain new
      information. The studies reviewed here suggest that this is due to overproduction
      of beta-amyloid. Both antibodies to beta-amyloid and specific antisense to the
      amyloid precursor protein reverse these deficits in the P8 mouse. This antisense
      can cross the blood brain barrier. It is hypothesized that the overproduction of
      beta-amyloid leads to a decline in Delta(9) desaturase activity with an
      alteration in membrane fatty acids. This results in altered membrane mobility
      leading to a decline in neurotransmitter activity and a decreased release of
      acetylcholine. This decreased cholinergic activity results in a decreased ability
      of the P8 mouse to learn and retain new information.

PMID- 11836013
TI  - Flow cytometric estimation of the plasma membrane diversity of bone marrow cells
      in mice treated with WR-2721 and cyclophosphamide.
AB  - The effects of S-2-/3-aminopropylamino/ethyl phosphorothioic acid (WR-2721,
      Amifostine) and cyclophosphamide (CP) on the cell surface exposure of
      phosphatidylserine (PS) and the plasma membrane impairment of bone marrow cells
      were assessed by flow cytometry assay with fluoresceinated annexin V (annexin V -
      FITC) and propidium iodide (PI). During the 96 h-period after treatment of adult
      male Swiss mice with WR-2721 (400 mg/kg b.wt.) and CP (200 mg/kg b.wt.), bone
      marrow cells expressing PS on the outer leaflet of the plasma membrane, which
      bound annexin V, and cells with a compromised cell membrane, which allowed PI to
      bind to the cellular DNA, were analysed. Temporary changes in the frequency of
      early apoptotic cells (annexin V - FITC positive/PI negative), late apoptotic and
      necrotic cells (annexin V - FITC positive/PI positive), and the number of live
      cells (annexin V - FITC negative/PI negative), were dependent on the drug(s)
      given. Application of CP distinctly triggered apoptotic and necrotic cell death,
      and WR-2721 pre-treatment of mice affected cell death induced by CP, causing
      reduction of the number of apoptotic and necrotic cells. The chemoprotective
      action of WR-2721 against PS externalisation and the plasma membrane impairment
      of normal bone marrow cells was shown.

PMID- 11836014
TI  - Immunohistochemical localization of thyroid stimulating hormone induced by a low
      oral dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin in female Sprague-Dawley rats.
AB  - We have investigated how a low dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)
      affects thyroid hormone regulation, especially in relation to the localization of
      thyroid stimulating hormone (TSH) in the pituitary and that of thyroxin (T4) of
      the thyroid in the rat. Female Sprague-Dawley rats were given a single oral
      administration of TCDD ranging from 1.0 to 4.0 microg/kg body weight (bw), and
      then tissue specimens were removed on day 7 post-administration. Thyroid hormone
      concentrations were measured in serum, and the expression of the TCDD-responsive
      genes, UDP-glucuronosyltransferase-1 (UGT1) and cytochrome P4501A1 (CYP1A1) were
      examined in the liver. TCDD administration resulted in an increase in both
      immunostaining intensity and the number of TSH-positive cells in the anterior
      pituitary. T4 was found to localize only in the follicular lumen of the thyroid
      in vehicle-treated control rats, while TCDD administration caused a foamy change
      in the colloid of some follicles, an indication of accelerating the biosynthesis
      of T4 in the thyroid. By morphometrical analysis, the ratio of
      parenchymal/lumenal area of the thyroid was found to increase in response to
      TCDD. TCDD treatment as low as 2.0 microg TCDD/kg bw induced a significant
      decrease in both serum total T4 (TT4) and free T4 (FT4) concentrations in the
      rats, with a significant increase in serum TSH levels in the 4.0 microg TCDD/kg
      bw rats. Serum total triiodothyronine (TT3) level was unchanged in all groups.
      The UGT1 gene was significantly induced at a TCDD dose as low as 1.0 microg/kg bw
      in a dose-dependent manner. TCDD concentrations in the serum, liver and adipose
      tissues were detected in a dose-related fashion. The present immunohistochemical
      results clearly support the earlier biochemical findings on the perturbation of
      the thyroid-pituitary axis by TCDD and suggest that UGT1 is an immediate target
      of a low TCDD exposure that triggers the perturbation.

PMID- 11836015
TI  - Alterations in ovarian follicular progesterone secretion by elevated exposures to
      the drinking water disinfection by-product dibromoacetic acid: examination of the
      potential site(s) of impact along the steroidogenic pathway.
AB  - Previous data from our laboratory indicated that the drinking water disinfection
      by-product, dibromoacetic acid (DBA), when applied in vitro to rat preovulatory
      follicles at a concentration consistent with blood levels found to disrupt
      estrous cyclicity, was able to block the stimulated secretion of progesterone.
      The present experiments focused on establishing a dose-response for such an
      effect and identifying the point(s)of impact of this compound along the
      steroidogenic pathway that underlie this suppression. Immature Sprague-Dawley
      rats were primed with PMSG on day 26 and killed 48 h later. Preovulatory
      follicles were removed and paired in culture with or without DBA (2-50 microg/ml)
      to reassess progesterone secretion under hCG-stimulated or baseline conditions.
      In addition, media supplemented with pregnenolone or 22(R)-hydroxycholesterol
      (22R-HC) were used to determine the effects of 50 microg/ml DBA on the initial
      steps leading to progesterone synthesis. Samples taken over the course of 24 h
      reaffirmed a significant DBA-associated suppression in baseline and stimulated
      progesterone release, while estradiol secretion was unaffected. This effect was
      mirrored by a reduction in follicular progesterone content in these DBA groups.
      The addition of pregnenolone eliminated this decrease, with the DBA-exposed
      follicles exhibiting a linear increase in progesterone release over the sampling
      period. The follicular progesterone content at 24 h showed that DBA treatment
      under pregnenolone supplementation caused marked elevations under both the hCG
      stimulated and non-stimulated conditions, something not reflected in the release
      data. Substitution of 22R-HC for pregnenolone eliminated the effect on baseline
      progesterone release, although the attenuation in stimulated secretion was still
      present. This suggests both an effect of DBA exposure on mitochondrial
      cholesterol transport by steroidogenic acute regulatory protein (StAR) and a
      possible impact on the receptor or postreceptor events triggered by hCG.

PMID- 11836016
TI  - DNA damage in tissues of rat treated with potassium canrenoate.
AB  - Potassium canrenoate (PC), a competitive aldosterone antagonist previously found
      to increase tumor incidence in rats and to produce genotoxic effects in in vitro
      systems, was examined in rats to acquire information on its genotoxic activity in
      vivo. Intragastric administration of 1/2 LD50 produced, as revealed by the Comet
      assay, a modest but statistically significant increase in the frequency of DNA
      lesions in liver but not in thyroid and bone marrow of male rats, and in thyroid
      and bone marrow but not in liver of female rats. In contrast with the frankly
      positive responses observed in primary cultures of rat hepatocytes (Martelli et
      al., Mutagenesis 14 (1999) 463-472) any evidence of DNA repair and micronuclei
      formation was absent in liver of rats treated with 1/2 LD50, and initiation of
      enzyme-altered liver preneoplastic lesions did not occur in the liver of rats
      given 100 mg/kg PC once a week for 6 successive weeks. A high and dose-dependent
      frequency of DNA lesions was found to occur in testes and ovaries of rats given
      single doses ranging from 1/8 to 1/2 LD50.

PMID- 11836017
TI  - Testicular toxicity of di-(2-ethylhexyl)phthalate in young Sprague-Dawley rats.
AB  - Di-(2-ethylhexyl)phthalate (DEHP), used widely in the manufacture of plastics, is
      a well-known reproductive toxicant. It causes apoptosis and loss of spermatogenic
      cells, resulting in testicular atrophy. Reports are scarce in the literature on
      the progression of apoptosis following repeated doses of phthalates. DEHP's
      mechanism of inducing testicular atrophy has been associated with depletion of
      zinc in the testis. ZnT-1 is a zinc transporter that is highly expressed in the
      testis. Thus, DEHP might exert its toxic effects on the testis by altering the
      expression of ZnT-1. In this regard, 25-day old Sprague-Dawley rats were given
      vehicle (5 ml corn-oil/kg, po) for 2, 7 and 14 days, or DEHP (2 g/5 ml corn
      oil/kg, po) daily, for 1, 2, 3, 5, 7, 10 and 14 days. Zinc content in testes was
      determined by atomic absorption spectrophotometry, and ZnT-1 mRNA was quantified
      by the branched DNA signal amplification method. Body weight gain and testicular
      weight (absolute and relative) were significantly lower in DEHP-treated rats.
      DEHP produced morphological changes in the testis, including apoptosis, necrosis,
      and loss of spermatogenic cells, which resulted in testicular atrophy. Apoptotic
      index (AI: the percentage of apoptotic cells in seminiferous tubules), determined
      using the TUNEL technique, was markedly increased after 1 day (AI: 2.9%, control
      AI: 0.1-0.3%) followed by a peak at 3 days (AI: 11.5%) and a gradual decrease
      till 10-14 days (AI: 7-9%). Zinc content in testis was not changed 1 day after
      DEHP administration, but decreased significantly at later time points. No
      difference was found in ZnT-1 mRNA expression between control and DEHP-treated
      animals until day 14. Our results suggest that apoptosis, along with necrosis,
      plays an important role in the mechanism of testicular atrophy by DEHP. In
      addition, ZnT-1 mRNA expression was not altered by DEHP and therefore, it appears
      that ZnT-1 cannot account for the decrease in testicular Zn content. Pathological
      lesions and apoptosis occurred prior to the loss of zinc in testis, suggesting
      that zinc depletion might be a secondary effect of DEHP-induced testicular
      toxicity, rather than the cause.

PMID- 11836019
TI  - The effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on the antioxidant system in
      mitochondrial and microsomal fractions of rat testis.
AB  - The ability of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) to induce oxidative
      stress in hepatic and some extrahepatic tissues of animals has been reported. The
      precise nature and mechanism of action of TCDD on the male reproductive system is
      not clear. In the present study, we have investigated the induction of oxidative
      stress in the testis of rat after exposure to low doses of TCDD. TCDD (1, 10, and
      100 ng/kg body weight per day) was administered orally to the rat for 45 days.
      After 24 h of the last treatment the rats were killed using anesthetic ether. The
      weights of the testis, epididymis, seminal vesicles and ventral prostate
      decreased while the body weight remained unchanged in the rats administered with
      TCDD. Mitochondrial and microsomal fractions of the testis were obtained by the
      method of differential centrifugation. The activity of antioxidant enzymes such
      as superoxide dismutase, catalase, glutathione reductase, and glutathione
      peroxidase decreased significantly in the animals treated with TCDD in a dose
      dependent manner in the mitochondrial and microsomal fractions of rat testis. The
      levels of hydrogen peroxide generation (H(2)O(2)) and lipid peroxidation
      increased in mitochondrial, and microsomal fractions of the testis. The results
      suggested that the low doses of TCDD elicit depletion of antioxidant enzymes and
      concomitant increase in the levels of H(2)O(2) and lipid peroxidation
      differentially in mitochondrial and microsomal fractions of rat testis. In
      conclusion the adverse effect of TCDD on male reproduction could be due to
      induction of oxidative stress.

PMID- 11836018
TI  - The effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on oxidative enzymes in
      adipocytes and liver.
AB  - Reactive oxygen species are produced in response to environmental toxins, and
      previous studies have suggested that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)
      damages a number of target organs through the generation of oxygen free radicals
      and oxidative stress. Upon exposure, TCDD becomes concentrated in adipose tissue,
      and adversely affects many organs, including liver. This study examined whether
      oxidative stress was induced in adipocytes and liver that were exposed to TCDD.
      3T3-F442A adipocyte cultures were treated with TCDD (5-200 nM) for up to 72 h,
      and the activity and mRNA levels of superoxide dismutase (SOD), catalase, and
      glutathione peroxidase (GSH-Px) in adipocyte cell lysates were measured. The
      addition of 50 nM TCDD induced a two-fold increase in SOD activity after 48 h
      (P<0.05). In contrast, TCDD had no significant effect on the activity of catalase
      or GSH-Px in the adipocytes, and the increase in SOD activity was not accompanied
      by a change in SOD mRNA levels. To assess the effects of TCDD on oxidative stress
      enzymes in vivo, male Sprague-Dawley rats were injected weekly for 8 weeks with
      30 ng/kg TCDD. In addition, the rats were fed either a low-fat complex
      carbohydrate (LFCC) diet, or a high fat sucrose diet (HFS). The HFS diet has
      previously been shown to induce mild obesity and insulin resistance, without
      inducing diabetes. SOD, catalase, and GSH-Px activities were measured in the
      liver and adipose tissue of these rats. TCDD injection resulted in a 52% decrease
      in catalase activity in the adipose tissue of HFS rats (P<0.05). In contrast, SOD
      and GSH-Px activities were not altered in adipose tissue of TCDD-injected rats.
      In liver, however, there were significant decreases in GSH-Px activity in
      response to TCDD. This effect of TCDD was observed in both the LFCC and HFS
      dietary groups. In addition, GSH-Px activity in the HFS rats was significantly
      decreased when compared to GSH-Px activity in LFCC rats, in both TCDD-treated and
      control groups, suggesting that TCDD and a high fat diet may combine to
      exacerbate oxidative stress. Thus, TCDD induces complex changes in enzymes of
      oxidative stress in both adipocytes and liver. In adipocytes, these changes
      occurred post-transcriptionally, as there were no changes in mRNA levels. In
      addition, a high fat diet per se also resulted in a decrease in GSH-Px activity
      in liver.

PMID- 11836020
TI  - Influence of redox-active compounds and PXR-activators on human MRP1 and MRP2
      gene expression.
AB  - In the present study, we investigated the inducibility of the drug conjugate
      transporter genes MRP1 and MRP2 by redox-active compounds such as tertiary
      butylated hydroquinone (tBHQ) and quercetin and by chemicals known to activate
      the pregnane X receptor (PXR) such as rifampicin and clotrimazol and by the
      metalloid compound arsenite. The human MRP2 gene was found to be inducible in
      HepG2 cells by rifampicin, clotrimazol, arsenite and tBHQ. As MRP1 expression is
      extremely low in HepG2 cells, its inducibility was studied in MCF-7 cells.
      However, only tBHQ and quercetin acted as inducers, but not the other compounds
      investigated. Reporter gene assays demonstrated that proximal promoter regions of
      the genes contribute to the induction by tBHQ, quercetin (MRP1) and clotrimazol
      (MRP2). However, the deletion of binding sites supposed to mediate the induction
      process (a PXR-binding element-like sequence for the clotrimazol effect and an
      ARE (antioxidative response element) for the tBHQ/quercetin effect) did not
      result in a significant decrease in the induction factor indicating that other
      parts of the promoter are probably involved in the induction process. In summary,
      expression of both genes can be up-regulated by redox-active compounds, while the
      other compounds tested induced only MRP2 but not MRP1 expression.

PMID- 11836021
TI  - Respiratory hypersensitivity in guinea pigs sensitized to 1,6-hexamethylene
      diisocyanate (HDI): comparison of results obtained with the monomer and
      homopolymers of HDI.
AB  - This study used guinea pigs that were sensitized to the biuret or isocyanurate
      type homopolymers of 1,6 hexamethylene diisocyanate (HDI). Induction was either
      by intradermal injection or repeated inhalation exposures. For comparison, groups
      of guinea pigs were sensitized to monomeric HDI. Naive animals served as negative
      controls. Two and three weeks following induction, animals were challenged by
      inhalation with the hapten and homologous protein conjugate of the hapten,
      respectively. Assessments were based on changes in respiratory rate, serum IgG(1)
      antibody titer, and influx of eosinophilic granulocytes in airways. Guinea pigs
      induced and challenged with the HDI-monomer did not display appreciable changes
      in respiratory rate, whilst the re-challenge with the HDI-protein conjugate
      caused unequivocal changes in respiratory patterns, including a marked bronchial
      influx of eosinophilic granulocytes. In contrast, animals induced and challenged
      with either the free or conjugated aerosols of HDI-homopolymers failed to elicit
      specific physiological or morphological pulmonary responses. IgG(1) antibodies
      were observed in all groups receiving monomeric HDI or HDI-homopolymers. Based on
      the comparative assessment of antibody titers following intradermal injections,
      it appeared that monomeric HDI was more potent to induce specific IgG(1)
      antibodies than the homopolymers of HDI. In summary, with respect to induction of
      allergy and asthma, the data presented here suggest that the homopolymeric forms
      of HDI appear to be less potent asthmagens, if any, than monomeric HDI.

PMID- 11836022
TI  - Interaction of fumonisin B(1) and aflatoxin B(1) in a short-term carcinogenesis
      model in rat liver.
AB  - The co-existence of the fumonisin and aflatoxin mycotoxins in corn merited
      studies to investigate their possible synergistic toxicological and carcinogenic
      effects. When utilising a short-term carcinogenesis model in rat liver, both the
      compounds exhibited slow cancer initiating potency as monitored by the induction
      of foci and nodules stained positively for the placental form of gluthatione-S
      transferase (GSTP(+)). However, when rats were treated in a sequential manner
      with AFB(1) and FB(1) the number and size of GSTP(+) lesions significantly
      increased as compared to the separate treatments. Histopathological analyses
      indicated that the individual treatments showed far less toxic effects, including
      occasional hepatocytes with dysplastic nuclei, oval cell proliferation and, in
      the case of FB(1), a few apoptotic bodies in the central vein regions. The
      sequential treatment regimen induced numerous foci and dysplastic hepatocyte
      nodules, and with oval cells extending from the periportal regions into the
      centrilobular regions. This would imply that, in addition to the cancer promoting
      activity of FB(1) of AFB(1)-initiated hepatocytes, the AFB(1) pre-treatment
      enhanced the FB(1) initiating potency, presumably by rendering the liver more
      susceptible to the toxic effects of FB(1). The co-occurrence of AFB(1) and FB(1)
      in corn consumed as a staple diet could pose an increased risk and should be
      included in establishing risk assessment parameters in humans.

PMID- 11836023
TI  - Evaluation of genotoxic effects in a group of workers exposed to low levels of
      styrene.
AB  - Occupational exposure to styrene was studied in a group of workers engaged in the
      production of fiberglass-reinforced plastics. Sister-chromatid exchanges (SCE),
      micronuclei (MN), and DNA damage (evaluated by means of comet assay) were
      measured in peripheral blood cells from the exposed workers and from a control
      population. Mandelic acid concentration, an indicator of styrene exposure level,
      was measured in urine samples collected at the end of the work shift. Average
      estimated values for styrene exposure were slightly below the threshold limit
      value (TLV) of 20 ppm recommended by the American Conference of Governmental
      Industrial Hygienists. Significant increases (P< or =0.01) have been found for
      SCE and MN frequencies and comet tail length among exposed individuals, as well
      as significant decreases (P< or =0.01) in the proliferation indices, as compared
      with control population. High correlation has been obtained between endpoints
      evaluated and exposure length, and increased values of SCE and MN frequencies and
      comet tail length have been found among smokers only in the exposed population.
      The high correlation obtained among SCE and MN frequencies and comet tail length,
      and the increase of these parameters in the exposed group with regard to control
      group justify the use of these three biomarkers in the evaluation of genotoxic
      effects in human populations exposed to styrene.

PMID- 11836024
TI  - The cytotoxic effect of mistletoe lectins I, II and III on sensitive and
      multidrug resistant human colon cancer cell lines in vitro.
AB  - Multidrug resistance glycoprotein1 (MDR-1) eliminates amphiphilic
      chemotherapeutic agents out of tumour cells leading to therapeutic failures. The
      aim of this study was to investigate the cytotoxic effect of mistletoe lectins
      (MLs) I, II and III on the sensitive human colon cancer cell line HT 29(mdr-),
      its multidrug resistant variant HT 29(mdr+), the variant HT 29(SF1m) transfected
      with the MDR-1 gene and its sensitive control cell line HT 29(deltaSF). Both cell
      proliferation and ML binding pattern were analysed. Marked quantitative
      differences concerning the cytotoxic effect of the three MLs on the different
      cell lines were observed. All MLs showed the greatest cytotoxicity towards the HT
      29(mdr+) cells, in which multidrug resistance (MDR) was induced by increasing
      concentrations of a MDR inducing agent. In contrast, MDR-1 and mock-transfected
      cells showed almost the same sensitivity towards the three MLs as the control
      cells (HT 29(mdr-)). FACS analysis showed that the HT 29(mdr+) cells were the
      cells with the highest density of ML binding sites. Thus, higher sensitivity of
      HT 29(mdr+) cells are not caused by the overexpression of MDR-1, but are caused
      by the general changes of the cellular glycosylation during the acquisition of
      the MDR phenotype.

PMID- 11836025
TI  - Role of the multidrug resistance protein 1 gene in the carcinogenicity of
      aflatoxin B1: investigations using mrp1-null mice.
AB  - The multidrug resistance protein 1 (MRP1) protects cells from xenobiotics by
      extruding from the intracellular compartment glutathione (GSH)-S-conjugates,
      glucuronyl conjugates and sulfate conjugates and by the co-export of
      xenobiotic(s) and GSH. An ATP-dependent transport of aflatoxin B1 (AFB1) and its
      GSH conjugates by MRP1 has been previously demonstrated in vitro. In the present
      study, we have sought to investigate the in vivo role of MRP1 in AFB1
      carcinogenicity, by comparing the incidence of tumors occurring in mrp1 (+/+) and
      mrp1 (-/-) mice 12 months after an 8 weeks exposure to AFB1. The carcinogen
      induced a similar number of lung and liver tumors in both strains. Most lung
      tumors were of the solid type and showed a moderate degree of differentiation in
      both mrp1 (+/+) and mrp1 (-/-) mice. These data provide direct evidence that in
      vivo MRP1 does not protect from AFB1 carcinogenicity. Due to the redundancy of
      transmembrane export pumps, other pump(s) may effectively vicariate for MRP1
      mediated transport of AFB1 and its glutathione conjugates.

PMID- 11836026
TI  - Uridine uptake inhibition assay: an automated micromethod for the screening of
      cytotoxicity.
AB  - The uridine uptake inhibition assay is a sensitive microassay for measuring
      cytotoxicity. This assay is normally performed with Hela S3 cells, which lack
      metabolic activity. In an earlier study, we adapted the test to HepG2 cells, a
      human hepatoma cell line that retains many hepatocyte characteristics, such as
      functional metabolic enzymes. This study describes a new automated protocol for
      the assay that makes it much more rapid. In the previous protocol, after the
      cells were treated with the test compounds and allowed to take up uridine for 30
      min, samples were taken manually one by one and spotted onto 3MM Whatman paper.
      After drying, the paper sheet was then chromatographed in 5% (P/V) TCA for 2 h in
      order to precipitate and measure the total amount of RNA. In the new method,
      instead of paper chromatography, samples are transferred onto a 96-well
      microplate equipped with GF/C glass filters. Then, RNA precipitation by TCA is
      carried out with a manifold system, and the amount of radiolabeled uridine taken
      up by the cells is counted directly with a radioactivity microplate reader. This
      method makes it possible to screen many compounds simultaneously for
      cytotoxicity. To evaluate its sensitivity, we compared the IC(50) values obtained
      with new and original protocol for each eight toxic compounds. We found an
      excellent correlation between the two methods (r(2)=0.99). With the automated
      protocol, the uridine uptake inhibition assay is both sensitive and rapid enough
      for high-throughput daily screening.

PMID- 11836027
TI  - Correlation between chromosome damage and apoptosis induced by fludarabine and
      idarubicin in normal human lymphocytes.
AB  - Fludarabine (FLU, a fluorinated purine analog) and idarubicin (IDA, a DNA
      topoisomerase II poison) are frequently used in cancer chemotherapy. The effects
      of these drugs on cultured normal human lymphocytes were studied to establish the
      possible involvement of chromosome damage in the apoptotic program. Chromosome
      aberrations (CA) were evaluated in first division metaphases and the apoptotic
      process was measured by morphological and electrophoretical techniques. The
      percentage of abnormal cells was increased from the doses of FLU 1.0 microg/ml
      and IDA 0.005 microg/ml (P<0.0001) with an important decrease in the mitotic
      index (MI) for the highest doses assayed. A significant dose-dependent induction
      of abnormal cells was observed for both drugs. An increase of apoptotic cells was
      found at 5.0 and 10.0 microg/ml of FLU (P<0.001) while IDA activated apoptosis at
      0.05 microg/ml (P<0.01) and markedly from 0.1 microg/ml (P<0.001). These
      increments were dose dependent. Apoptotic cell morphology was associated with DNA
      fragmentation at the highest doses. The increased induction of abnormal cells and
      the decreased MI were in correlation with the apoptotic index for FLU and IDA,
      suggesting the role of CA in drug-induced cell death.

PMID- 11836028
TI  - Evaluation of the Leishmania recombinant K39 antigen as a diagnostic marker for
      canine leishmaniasis and validation of a standardized enzyme-linked immunosorbent
      assay.
AB  - Canine infections with Leishmania infantum are important as a cause of serious
      disease in the dog and as a reservoir for human visceral leishmaniasis (VL).
      Accurate diagnosis of canine infections is essential to the veterinary community
      and for VL surveillance programs. A standardized ELISA using a purified
      recombinant antigen (rK39) specific to VL was compared to the immunofluorescent
      antibody test (IFAT) as the standard. The ELISA was developed, optimized and
      evaluated using sera from 6368 dogs. The standardized ELISA and IFAT results were
      highly concordant. The timing and pattern of ELISA and IFAT seroconversion in
      dogs followed prospectively after natural infections were very similar.
      Antibodies reacting with rK39 were more common in asymptomatic canine infections
      than reported for subclinical human VL. The rK39 ELISA is a relatively simple and
      rapid assay for assessing the infection status of dogs, and is an alternative to
      IFAT, especially when screening large numbers of samples.

PMID- 11836029
TI  - Prevalence and analysis of potential risk factors for Cryptosporidium parvum
      infection in lambs in Zaragoza (northeastern Spain).
AB  - An epidemiologic study was carried out to investigate the prevalence of and to
      identify factors associated with the risk of Cryptosporidium infection in sheep
      in Zaragoza (northeastern Spain). Faecal samples from 583 lambs aged from 1 day
      to 3 months and 205 ewes older than 1 year were collected at 89 farms in the two
      regions of the province of Zaragoza with the highest sheep population (Zaragoza
      and Ejea de los Caballeros). In every sheep farm, data of the factors potentially
      associated with the likelihood of C. parvum infection were analysed: geographical
      location, season, size of herd, number of lambs in the herd at sampling time,
      lambing period, cleaning of lambing area and presence of diarrhoeic lambs in the
      farm. C. parvum oocysts were identified by using the Ziehl-Neelsen technique in
      344 lambs (59%) from 75 farms (84.4%). Infected lambs ranged from less than 7
      days to 90 days of age, although the percentage of animals shedding oocysts
      peaked at 8-14 days of age (76.2%). Statistical analysis showed that infection
      rates were significantly higher in lambs aged between 1 and 21 days (66.4%) than
      in those aged between 22 and 90 days (23%) (P<0.0001, chi(2)). Analysis of
      correlation between excretion of oocysts and diarrhoea revealed a relationship in
      all age groups and the probability of presenting diarrhoea was significantly
      higher for lambs shedding oocysts (86.3%) than for those which did not excrete
      the parasite (32.2%) (P<0.0001, chi(2)). Similarly, cryptosporidial infection
      rates were significantly higher in diarrhoeic (79.4%) than in non-diarrhoeic
      lambs (22.4%). Furthermore, infection intensity was correlated with the presence
      of clinical symptoms. Presence of diarrhoeic lambs in the farm was the only
      factor significantly associated with an increased risk of infection since the
      percentage of herds testing positive was significantly higher in farms with
      diarrhoeic lambs (91.3%) than in those without cases of neonatal diarrhoea
      (12.5%) (P<0.0001, chi(2)). Factors associated with a decreased risk of C. parvum
      infection in lambs included low numbers of lambs in the farm and cleaning of the
      lambing area. Additionally, lambs 8-14 days of age were less likely to be
      infected at the first lambing period and in spring/autumn. Cryptosporidial
      infection was also detected in 16 ewes (7.8%) which excreted few oocysts and
      without diarrhoea.

PMID- 11836030
TI  - Screening of dogs for Echinococcus granulosus coproantigen in a low endemic
      situation in Cyprus.
AB  - In the framework of an echinococcosis surveillance and control programme in
      Cyprus, a commercial enzyme-linked immunosorbent assay (ELISA) (CHEKIT
      ECHINOTEST) designed for the detection of Echinococcus granulosus and E.
      multilocularis coproantigens was used in 1997-2000 for the investigation of large
      numbers of dogs. Most of the animals originated from areas where approximately
      0.2% of the dogs had been found to be infected with E. granulosus in previous
      (1993-1996) arecoline surveys. The sensitivity of the coproantigen test was 83%,
      as determined in 35 dogs naturally infected with this cestode species. The
      specificity was 98% in 97 randomly selected dogs from Cyprus, but it was reduced
      to 80% in a group of 50 dogs, infected with Taenia spp. A total of 6551 dogs
      (mainly of rural origin) was examined, including three large groups (N: 2928,
      1761 and 1800) from the Government Control Area (GCA) in southern Cyprus and a
      small group (N: 62) from the Non-Government Control Area (NonGCA) in the northern
      part of the island. Among the dogs from the GCA, 184 (2.8%) tested positive for
      coproantigen; coproantigen prevalences were 2.6, 4.9 and 1.1% in these three
      groups, and of 62 dogs from the NonGCA 8.1% were positive. The calculated true
      prevalences of E. granulosus in the dog population of the GCA ranged between 0.0
      and 3.58%. The predictive values of the test, based on a 0.2% prevalence, was
      >99.9% for negative results, but very low (7%) for coproantigen-positive results.
      However, the relatively small number of coproantigen-positive dogs can be treated
      with praziquantel or the results can further be confirmed by arecoline purging.

PMID- 11836031
TI  - Experimental concurrent infection of sheep with Oestrus ovis and Trichostrongylus
      colubriformis: negative interactions between parasite populations and related
      changes in the cellular responses of nasal and digestive mucosae.
AB  - Concurrent infections of sheep with Oestrus ovis and trichostrongyles of the
      digestive tract are common in the field. In order to examine the possible
      occurrence of interactions between these two parasites and the consequences on
      parasite biology and the associated pathophysiological changes, an experimental
      study was conducted on four groups of naive sheep. Group O was infected
      repeatedly with O. ovis larvae from D0 to D42 of experiment; group T received a
      single infection of Trichostrongylus colubriformis on D49; sheep from group OT
      received both infections, and animals from group C remained uninfected as
      controls. Parasitological and pathophysiological parameters were measured
      regularly. At necropsy (D94), the mucosal cellular responses in the nasal
      cavities and digestive tract from all animals were analysed from histological
      sections. Infection of the digestive tract with nematodes did not modify the
      biology of Oestrus populations. In contrast, the presence of O. ovis was related
      to significant reductions in nematode egg excretion, worm fecundity and worm
      burdens. These changes were associated with significant modifications in tissular
      populations of mast cells, globule leucocytes and eosinophils in the respiratory
      and digestive tracts. These results indicate that parasitic infection in one
      particular anatomical site induces "at distance" inflammatory reactions of the
      whole mucosal system. The relationships between the cellular response and the
      changes in worm biology are discussed.

PMID- 11836032
TI  - Persistent activity of moxidectin pour-on and injectable against sucking and
      biting louse infestations of cattle.
AB  - To evaluate the persistent activity of pour-on and injectable moxidectin against
      natural challenge by sucking (predominantly Linognathus vituli) and chewing
      (Bovicola bovis) cattle lice, 96 mixed-breed calves that had been treated to
      remove all lice were blocked by body weight and randomly allocated to three
      treatments: untreated control, moxidectin at 500 microg/kg by topical application
      and moxidectin at 200 microg/kg by subcutaneous injection. Twelve pens were
      blocked into groups of four and randomly allocated to four challenge times: 14,
      21, 28 and 35 days post-treatment. Treatment groups were assigned to challenge
      pens randomly. Two donor calves, with demonstrated infestations of both sucking
      and chewing lice, were introduced into each pen containing eight principal calves
      at the start of each challenge time. Donors remained in the challenge pen for 7
      days. Principal calves were examined for lice, 7, 14, 21 and 28 days after donor
      removal using a standardized hair-parting technique. Moxidectin injectable
      prevented re-infestation with L. vituli for up to 42 days, but did not provide
      persistent activity against B. bovis longer than 35 days post-treatment.
      Moxidectin pour-on demonstrated persistent activity against both B. bovis and L.
      vituli for 42 days.

PMID- 11836033
TI  - Effect of level of feed intake on the development of gastrointestinal parasitism
      in growing lambs.
AB  - A study was conducted to examine the role of nutrition in the development of
      gastrointestinal (GI) parasitism, performance and pathophysiology of parasitism
      in female lambs. Forty-four months old ewe lambs received for 6 weeks 0, 1500 or
      7000 L(3) larvae of Teladorsagia circumcincta in two doses per week. The animals
      were given access to a pelleted diet to meet energy requirements for gaining
      weight close to their potential (H) or approximately 50% of it (L). The level of
      protein in the diet was 20-30% above requirements for both planes of nutrition.
      Measurements of body weight, serum pepsinogen concentration and faecal egg counts
      were taken at weekly intervals. All animals were slaughtered 2 weeks after the
      last larval dosing for estimation of worm count, carcass composition and
      reproductive tract development. Voluntary intake of infected animals decreased by
      approximately 10%. Both nutrition and infection influenced lamb performance and
      carcass composition. However, no direct effects on reproductive tract parameters
      due to the presence of infection were observed. The level of L(3) infection
      showed a significant effect not only on faecal egg counts and on worm burden, as
      it could be expected, but also on the proportion of females to males, which
      increased significantly with the level of infection. While the plane of nutrition
      did not show a significant effect on faecal egg counts or on worm burden,
      surprisingly, both female worm size and their fecundity decreased significantly
      with the level of nutrition. This response was accompanied by a significant
      increase in the concentration of circulating eosinophils suggesting that the
      immune response of lambs consuming high levels of energy was enhanced compared to
      that of lambs kept on a restricted diet. Results herein show that in young female
      lambs fed on adequate levels of protein, an improvement in energy supply does not
      only improve carcass characteristics but clearly enhances the development of
      resistance to GI nematodes infection. This may have decisive management
      implications for the control of parasitic infections in sustainable production
      systems.

PMID- 11836034
TI  - Sub-clinical parasitism in spring-born, beef suckler calves: epidemiology and
      impact on growth performance during the first grazing season.
AB  - Sub-clinical parasitism in spring-born single suckled beef calves was
      investigated from the middle of their first grazing season until weaning or
      housing later the same year. The study was conducted on four beef suckler herds
      in southern England over a 3-year period and involved a total of 334 spring-born
      beef suckler calves and their dams. The animals were grazed extensively on
      pastures naturally infected with nematode larvae. At the start of each period of
      observation, faecal samples were taken from calves and cows and subjected to
      routine worm egg counts; calves were re-sampled at the end of the grazing season.
      In July in each year and at each location the calves were ranked by initial
      weight within sex, paired according to rank and randomly allocated to either an
      untreated control group or a group in which the calves were each treated with an
      ivermectin sustained-release (SR) bolus. The calves in both trial groups, and
      their dams, were grazed together until weaning or housing. The calves were
      weighed at the initial allocation and at the end of the study. The adult cows
      were not treated with any anthelmintic during the study. The faecal nematode egg
      counts (FECs) conducted in July showed that the suckler cows were excreting worm
      eggs at low concentrations: range 0-100 eggs per gram (epg), with one individual
      count of 500epg, 88% of the cows sampled had counts of <50epg. Similarly, the
      counts from the calf samples were fairly low in July: range 0-250epg, 73% of the
      calves sampled had counts of <50epg. By the end of the grazing season, the faecal
      samples from the untreated control calves showed higher values: range 0-650epg,
      with only 58% having an epg of <50. The average rate of daily liveweight gain in
      the untreated heifer calves was 0.79kg per day, the corresponding figure for the
      heifer calves treated with the ivermectin SR bolus in mid-summer was 0.88kg per
      day; the difference of 90g per day was significantly different (P=0.0118). The
      average rate of daily liveweight gain in the untreated bull calves was 0.91kg per
      day, the corresponding figure for the bull calves treated with the ivermectin SR
      bolus in mid-summer was 1.01kg per day; the difference was significantly
      different (P=0.0169).

PMID- 11836035
TI  - Production of antibodies to recombinant antigens from Lucilia cuprina following
      cutaneous immunisation of sheep.
AB  - Immunological control of cutaneous myiasis of sheep caused by Lucilia cuprina
      larvae has been an elusive goal. Antibody to antigens derived from the
      peritrophic membrane can stunt or kill larvae in a dose dependent fashion. Thus
      efficacy of vaccines employing these antigens may be limited by the amount of
      antibody in skin available for ingestion by larvae. The potential for elevating
      antibody concentrations in skin by intradermal immunisation with the recombinant
      peritrophic membrane antigens peritrophin-44, peritrophin-48 and peritrophin-95
      was therefore examined. Using within-animal comparisons, specific antibody was
      significantly higher in skin transudates from locally immunised sites than from
      adjacent adjuvant control sites. It was concluded that cutaneous immunisation may
      assist immunological control of blowfly larvae.

PMID- 11836036
TI  - Humoral immune response to Dipylidium caninum infection of stray dogs in Taiwan.
AB  - Two kinds of homogeneous proglottid, mature and gravid, of Dipylidium caninum
      were used as the antigens for immunodiagnosis of canine dipylidiosis in stray
      dogs in Tainan, Taiwan. The ELISA was performed on 30 serum samples; 24 from
      dipylidiosis, four from ancylostomosis and two from toxocariosis. The ELISA have
      specificity and sensitive of 100 and 50% for mature proglottid extract, and 75
      and 100%, respectively, for gravid proglottid extract. EITB technique showed two
      major peptide bands of 94.8 and 97.9kDa were recognized in the sera pool of
      infected dogs.

PMID- 11836038
TI  - Compliance with 10 years oral hormonal replacement therapy.
AB  - OBJECTIVE: To study 10 years compliance with oral hormonal replacement therapy
      (HRT). METHODS: One hundred and fifty-one early postmenopausal women were
      initially randomly allocated to three groups in a double blind, 2-year placebo
      controlled trial. Fifty women received continuous combined therapy, 50 were
      placed on sequential therapy, while the last 51 women were given placebo for 2
      years and after that no therapy. After the trial, the women were followed in an
      open investigation for a total of 10 years. RESULTS: One hundred and twenty-six
      women (83%) out of 151 came to a 10-year interview, 4% had died and the remaining
      did not want to participate. None of the women in the combined group had changed
      to other regimens (42% were still in treatment after 10 years). Twenty-four
      percent from the original sequential group were still in sequential therapy;
      another 24% of the group had changed to other HRTs (mainly because the women
      disliked the monthly bleedings). Fifty-three percent of the women from the
      placebo group had not received any HRT. Eighteen percent were on HRT. Eighty
      seven percent of the women who had taken combined therapy for 8 years were still
      being treated at the tenth years' visit. CONCLUSION: Long-term compliance was
      excellent for continuous combined therapy and better than for sequential after 10
      years.

PMID- 11836039
TI  - Menopause in Morocco: symptomatology and medical management.
AB  - OBJECTIVES: To assess the frequency of menopausal symptoms and patterns of
      recourse to medical care in Rabat, Morocco. METHODS: Face to face interviews with
      a representative sample of 300 women aged 45-55 years; information was collected
      on socio-demographic variables, reproductive history, use of health care, symptom
      checklist, and medical management of menopause. RESULTS: The most frequent
      complaints are fatigue and hot flashes, each reported by 61% of women, headaches
      (57%), joint pain (54%), anxiety (44%) and irritability (42%). Hot flashes, but
      not cardiovascular symptoms, are statistically associated with menopausal status.
      Only 5% of women in the sample take hormones, and 4% calcium; 13% continue to
      take contraceptives. The frequency of some symptoms and the use of health care
      for menopause are influenced by socio-economic factors. CONCLUSIONS: Reports of
      hot flashes and joint pains are relatively high, but the frequency of use of
      medical services for menopause is low.

PMID- 11836040
TI  - The effects of a soy rich diet on serum lipids: the Menfis randomized trial.
AB  - OBJECTIVE: To assess beneficial effects of a soy rich diet on the main biomarkers
      of cardiovascular health in menopause, compared with the effects of the hormone
      replacement therapy (HRT). METHODS: 187 healthy asymptomatic postmenopausal
      women, aged 39-60, were recruited and randomized into three groups: a soy rich
      diet group, a HRT group, and a control group. Lipid profile, body mass index,
      blood pressure, endometrial thickness, uterine artery resistance index (RI), were
      evaluated in all the participants at the baseline, after 6 months, and at the end
      of the study. RESULTS: After a 6-month intervention period, the lipid profile in
      the soy rich diet group showed a favourable outcome, similar to that observed in
      the HRT group, but compliance to the diet was low. CONCLUSION: Soy products may
      be used in the prevention of cardiovascular risk in postmenopausal women because
      of their efficacy in contrasting the negative effects of menopause on the
      cardiovascular system, but our findings should be confirmed; moreover, suitable
      strategies to improve the compliance have to be considered.

PMID- 11836041
TI  - A 2-year, randomized, comparative, placebo-controlled study on the effects of
      raloxifene on lipoprotein(a) and homocysteine.
AB  - OBJECTIVES: Lipoprotein(a) (Lp(a)) and homocysteine (Hcy) are independent
      cardiovascular risk factors, which have been shown to be lowered by hormone
      replacement therapy (HRT). In this 2-year study, the long-term effects of
      raloxifene (Rlx) in two doses, on Lp(a) and Hcy, were studied and compared with
      the effects of continuously combined hormone replacement therapy (ccHRT).
      METHODS: In a prospective, randomized, double-blind, placebo-controlled 2-year
      study, 95 healthy, non-hysterectomized, early postmenopausal women, received
      daily either oral Rlx 60 mg (N=24) or 150 mg (N=23), ccHRT (conjugated equine
      estrogens 0.625 mg plus medroxyprogesterone acetate 2.5 mg; N=24) or placebo
      (N=24). Fasting serum Lp(a) and plasma Hcy concentrations were measured at
      baseline and at 6, 12 and 24 months. RESULTS: The mean individual changes
      compared to baseline after 24 months were for Lp(a): Rlx 60: - 5%, Rlx 150: -7%,
      ccHRT: -34%, placebo: +1% and for Hcy: Rlx 60: -3%, Rlx 150: -4%, ccHRT: -4%,
      placebo: +6%. ANCOVA was significant for Lp(a) under ccHRT versus placebo
      (P=0.001) and for Lp(a) under ccHRT versus each of the two Rlx groups (P<0.05).
      CONCLUSIONS: Long-term treatment with Rlx was not as effective as ccHRT in
      lowering Lp(a). Although not significant and without an obvious dose-related
      response, the Hcy values showed the same trend for each treatment arm, which is
      in line with data reported earlier.

PMID- 11836042
TI  - Comparative endometrial histology in postmenopausal women with sequential hormone
      replacement therapy of estradiol and, either chlormadinone acetate or micronized
      progesterone.
AB  - OBJECTIVES: To determine the endometrial response in postmenopausal women treated
      with a sequential hormone replacement therapy (HRT) of estradiol and, either
      chlormadinone acetate (CA) or micronized progesterone (MP). METHODS: Three
      hundred and thirty-six postmenopausal women with a normal endometrium were
      randomized in the double-blind study. All patients received percutaneous
      estradiol 1.5 mg/day from day 1 to day 24 and either CA 10 mg/day or oral MP 200
      mg/day from day 10 to day 24. The total duration of treatment was 18 months.
      Endometrial biopsies were performed before treatment and between day 18 and day
      24 of the 18th month of HRT. RESULTS: Of the 336 patients selected, 317 had a
      biopsy at inclusion. Of them, 244 patients (124 in the CA group and 120 in the P
      group) were suitable for evaluation for analysis at the 18th month. Insufficient
      sampling occurred in 33.9% in the CA group and 60% in the MP group (probably
      atrophic). No case of hyperplasia could be reported in both groups. The
      endometrium was atrophic in 19.5 versus 27.1%, proliferative in 3.7 versus 8.3%
      and secretory in 76.8 versus 62.5% in CA and MP groups, respectively. It was
      possible to see histological differences induced by the two progestins. The CA
      endometria showed fewer glands lined by a cubo-cylindrical epithelium, with an
      edematous stroma, compared to the MP endometria which had more glands lined by a
      cylindrical epithelium, stroma being poorly edematous. These figures varied in
      intensity due to the length of progestative impregnation, predecidualization
      occurring later in the CA group, with distended capillaries. CONCLUSIONS: These
      results show that CA 10 mg/day is a powerful progestin compared to MP 200 mg/day,
      on weakly estradiol-primed endometria, giving a molecule-specific histological
      aspect with a good endometrial safety.

PMID- 11836043
TI  - The efficacy of two dosages of a continuous combined hormone replacement regimen.
AB  - OBJECTIVES: To evaluate the efficacy of a low-dose combination of estradiol (E2)
      and norethisterone acetate (NETA) on bone markers, lipid and bleeding profiles
      and menopausal symptoms. METHOD: Ninety-six healthy Chinese postmenopausal women
      were allocated randomly to receive 1 mg E2/0.5 mg NETA (low-dose hormone
      replacement therapy (HRT)) or 2 mg E2/1 mg NETA (high-dose HRT) for 6 months.
      RESULTS: Bone resorption markers (collagen I N-terminal telopeptides (NTX) and
      deoxypyridinoline (dPyr)) were significantly reduced; -66 and -32%, respectively,
      in high-dose HRT versus -55 and -24%, respectively, in low-dose HRT. Bone
      specific alkaline phosphatase remained unchanged with either combination of
      hormones. Total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C)
      levels were decreased significantly (-12 and -13%, respectively, in high-dose HRT
      vs. -7 and -8% in low-dose HRT). High density lipoprotein cholesterol (HDL-C) was
      decreased to a lesser extent in low-dose HRT and triglycerides (TG) levels
      remained unchanged. Both the low and high-dose HRT were effective in alleviating
      menopausal symptoms. After 6 months of treatment, 2% of women in the low-dose HRT
      were bleeding compared with 23% in the high-dose HRT. Breast pain occurred in 2%
      of women in low-dose HRT compared with 15% in high-dose HRT. The endometrium in
      the majority of the women remained normal. CONCLUSION: Menopausal symptoms were
      reduced effectively in postmenopausal women on either low-dose or high-dose HRT.
      TC, LDL-C levels and bone resorption markers were reduced in a dose-dependent
      manner. Low-dose HRT provided a better bleeding profile and the incidence of
      breast pain was low.

PMID- 11836044
TI  - Effect of tibolone compared with sequential hormone replacement therapy on
      carbohydrate metabolism in postmenopausal women.
AB  - OBJECTIVE: To investigate the effects of tibolone on carbohydrate metabolism, and
      to compare these effects with those of a sequential regimen of conjugated equine
      estrogens and medrogestone. METHODS: This was an open-label, multicentre,
      comparative study. Seventy-two postmenopausal women were randomized to receive
      either tibolone 2.5 mg/day or conjugated equine estrogens 0.6 mg plus sequential
      medrogestone 5 mg (CEE/M) for six 28-day cycles. Carbohydrate metabolism was
      evaluated at baseline and after three and six cycles of treatment by an oral
      glucose tolerance test (OGTT). A blood sample was taken at 30, 60, 90 and 120 mm
      after glucose 75 mg dosing for determination of plasma glucose, insulin and
      connecting peptide (C-peptide) levels. RESULTS: The changes from baseline of
      glucose, insulin and C-peptide area-under-the-curve (AUC) values were not
      statistically significant after 3 and 6 months of tibolone or CEE/M treatment.
      There was a small transitory decrease in HbA(1C) after three cycles of treatment
      with tibolone. CONCLUSION: The effects of tibolone and CEE/M on carbohydrate
      metabolism were considered to have no clinical significance.

PMID- 11836045
TI  - The effect of low-dose conjugated equine estrogens and cyclic MPA on bone
      density.
AB  - OBJECTIVE: to compare the effect of 0.3 and 0.625 mg conjugated equine estrogens
      on bone mineral density (BMD) in a private practice setting. METHODS:
      postmenopausal women interested in hormone replacement therapy were prescribed
      either 0.3 or 0.625 mg conjugated equine estrogens daily with 10 mg
      medroxyprogesterone acetate days 1-12 of the month. All women were given calcium
      citrate 1000 mg/day and vitamin D 400 IU/day. DEXA bone mineral density studies
      of the spine and hip were performed at baseline and 1 year. RESULTS: there was no
      significant difference in BMD at the spine, the trochanter or the femoral neck
      compared with baseline in either the 0.625 or 0.3 mg group. The mean percent
      increase in BMD for the 0.3 versus 0.625 mg group was: spine 2.6 versus 3.8%,
      femoral neck 1.8 versus 1.5%, and trochanter 0.5 versus 2.6%. CONCLUSION: both
      the 0.625 mg dose and the 0.3 mg dose of conjugated equine estrogens preserved
      BMD at the spine and hip over one year in early postmenopausal women who were
      also given cyclic medroxyprogesterone acetate, calcium citrate and vitamin D.

PMID- 11836046
TI  - Risk of calcium oxalate nephrolithiasis in postmenopausal women supplemented with
      calcium or combined calcium and estrogen.
AB  - BACKGROUND: Recent studies showed that postmenopausal women lost less bone mass
      when supplemented with calcium or estrogen therapy. However, the safety of the
      treatments in terms of the risk of calcium oxalate stone formation is unknown. We
      therefore conducted this study to determine the alteration in calcium oxalate
      supersaturation after calcium supplement or after combined calcium and estrogen
      therapy in postmenopausal osteoporotic women. METHODS: Fifty-six postmenopausal
      women were enrolled in this study. All subjects were more than 10 years
      postmenopausal with vertebral or femoral osteoporosis by bone mineral density
      criteria. They were randomly allocated to receive either 625 mg of calcium
      carbonate (250 mg of elemental calcium) at the end of a meal three times a day
      (group A, n=26) or calcium carbonate in the same manner plus 0.625 mg/day of
      conjugated equine estrogen and 5 mg medrogestone acetate from day 1-12 each month
      (group B, n=30). The age (mean +/- S.E.M.) was 66.3 +/- 1.2 and 65.1 +/- 1.1
      years, weight 54.1 +/- 1.2 and 55.3 +/- 2.1 kg, in group A and group B,
      respectively. Urine specimens (24-h) were collected at baseline and 3 months
      after treatment for the determination of calcium oxalate saturation by using
      Tiselius's index (AP(CaOx)) and calcium/citrate ratio. RESULTS: After 3 months of
      treatment, there was no significant alteration from baseline for urinary
      excretion of calcium, citrate and oxalate. Urinary phosphate excretion was
      significantly reduced (6.3 +/- 0.7 vs. 5.1 +/- 0.7 mmol/day for group A and 8.2
      +/- 0.9 vs. 5.8 +/- 0.7 mmol/day for group B, P<0.05), whereas net alkaline
      absorption was significantly elevated (10.1 +/- 3.6 vs. 20.1 +/- 4.4 meq/day for
      group A and 4.8 +/- 3.2 vs. 19.9 +/- 3.6 meq/day for group B, P<0.05).
      Calcium/citrate ratio and AP(CaOx) determined at baseline were not different from
      the corresponding values after treatment in both groups; calcium/citrate: 10.1 +/
      3.1 vs. 10.1 +/- 2.5 for group A and 9.3 +/- 1.8 vs. 11.9 +/- 2.5 for group B
      and AP(CaOx): 1.1 +/- 0.1 vs. 1.3 +/- 0.2 for group A and 1.2 +/- 0.2 vs. 1.1 +/-
      0.1 for group B. There were eight and nine patients with high AP(CaOx), or >2, at
      baseline and after treatment, respectively. CONCLUSIONS: Calcium supplement with
      a meal or combined calcium supplement and estrogen therapy is not associated with
      a significant increased risk of calcium oxalate stone formation in the majority
      of postmenopausal osteoporotic patients. Determination of urinary saturation for
      calcium oxalate after calcium and estrogen supplements, especially at the initial
      phase of treatment, may be helpful in the avoidance of nephrolithiasis.

PMID- 11836048
TI  - Simultaneous LC determination of paracetamol and related compounds in
      pharmaceutical formulations using a carbon-based column.
AB  - A simple, rapid and convenient high performance liquid chromatographic method,
      which permits the simultaneous determination of paracetamol, 4-aminophenol and 4
      chloracetanilide in pharmaceutical preparation has been developed. The
      chromatographic separation was achieved on porous graphitized carbon (PGC) column
      using an isocratic mixture of 80/20 (v/v) acetonitrile/0.05 M potassium phosphate
      buffer (pH 5.5) and ultraviolet detection at 244 nm. Correlation coefficient for
      calibration curves in the ranges 1-50 microg ml(-1) for paracetamol and 5-40
      microg ml(-1) for 4-aminophenol and 4-chloroacetanilide were >0.99. The
      sensitivity of detection is 0.1 microg ml(-1) for paracetamol and 0.5 microg ml(
      1) for 4-aminophenol and 4-chloroacetanilide. The proposed liquid chromatographic
      method was successfully applied to the analysis of commercially available
      paracetamol dosage forms with recoveries of 98-103%. It is suggested that the
      proposed method should be used for routine quality control and dosage form assay
      of paracetamol in pharmaceutical preparations. The chromatographic behaviour of
      the three compounds was examined under variable mobile phase compositions and pH,
      the results revealed that selectivity was dependent on the organic solvent and pH
      used. The retention selectivity of these compounds on PGC was compared with those
      of octadecylsilica (ODS) packing materials in reversed phase liquid
      chromatography. The ODS column gave little separation for the degradation product
      (4-aminophenol) from paracetamol, whereas PGC column provides better separation
      in much shorter time.

PMID- 11836047
TI  - Estrogen replacement reverses ovariectomy-induced vaginal hyperalgesia in the
      rat.
AB  - OBJECTIVES: The loss of ovarian function in women through aging or oophorectomy
      is often associated with the development of vaginal hyperalgesia that can be
      alleviated with estrogen replacement. This study examined if ovariectomy in rats
      would similarly give rise to vaginal hyperalgesia, and, if so, whether estrogen
      replacement would alleviate it. METHODS: Female rats were trained to perform an
      operant response to escape vaginal distention delivered by inflating a balloon
      located in mid-vaginal canal. Percent escape responses to eight different volumes
      of distention measured in normally cycling rats were compared with measures made
      in the same rats following ovariectomy (OVX) or sham ovariectomy (shamOVX), and
      then, in the OVX group, estrogen replacement (OVX+E2). Pressures exerted by the
      eight volumes on the vaginal wall were also measured, thereby permitting
      assessment of vaginal tone. RESULTS: Whereas overall escape response percentages
      after OVX, but not shamOVX, were significantly higher to the largest six
      distention volumes compared with responses during cycling, there were individual
      differences in the amount of hyperalgesia. Following OVX+E2, escape response
      percentages decreased in all but one rat. Vaginal tone after OVX, shamOVX or
      OVX+E2 did not differ from overall vaginal tone in cycling rats. CONCLUSIONS:
      Ovariectomy in rats evokes a variable amount of vaginal hyperalgesia that can be
      alleviated by estrogen replacement in most cases. Thus, the ovariectomized rat
      appears to provide a useful model for the study of mechanisms underlying the
      dyspareunia that is associated with loss of ovarian function in women.

PMID- 11836050
TI  - Preparation of a cimetidine ion-selective electrode and its application to
      pharmaceutical analysis.
AB  - A novel cimetidine ion-selective electrode is prepared, characterized and used in
      pharmaceutical analysis. The electrode incorporates PVC-membrane with cimetidine
      phospohotungstate ion pair complex. The electrode exhibits a Nernstian response
      for cimetidine in the concentration range 1.0 x 10(-5)-1.0 x 10(-2) M with a
      slope of 58+/-1 mV per decade. The limit of detection is 5.0 x 10(-6) M. The
      electrode displays a good selectivity for cimetidine with respect to a number of
      common foreign inorganic and organic species. It can be used in the pH range 3.0
      5.5. The membrane sensor was successfully applied to the determination of
      cimetidine in its tablets as well as its recovery from a urine sample.

PMID- 11836049
TI  - A rapid colorimetric method for the determination of Losartan potassium in bulk
      and in synthetic mixture for solid dosage form.
AB  - Two new rapid reproducible and economical spectrophotometric methods are
      described for the determination of Losartan potassium in bulk and in synthetic
      mixture for solid dosage forms. Both methods are based on the formation of an
      orange-red and orange ion-pair complex due to the action of Calmagite (CT) and
      Orange-II (O-II) on Losartan potassium in acidic medium (pH 1.2). Under optimised
      conditions, they show an absorption maxima at 491 nm (CT) and 486 nm (O-II), with
      molar absorptivities of 1.74 x 10(3) and 1.75 x 10(3) l mol(-1) cm(-1) and
      Sandell's sensitivities of 0.2649 and 0.2637 per 0.001 absorbance unit for CT and
      O-II, respectively. The colour is stable for 5 min after extraction. In both
      cases Beer's law is obeyed between 10 and 100 microg ml(-1). The proposed method
      was successfully extended to synthetic mixture for solid dosage forms.

PMID- 11836051
TI  - Fortum stability in different disposable infusion devices by pyridine assay.
AB  - The stability of ceftazidime in 5% dextrose injection and 0.9% sodium chloride
      injection when stored in a different disposable infusion device was determined.
      Solutions of ceftazidime 40 mg/ml were used to fill the drug administration
      devices. Stability was determined for both 5% dextrose injection and 0.9% sodium
      chloride injection solutions at 37 degrees C in four disposable infusion devices.
      Ceftazidime and its mean degradation product, pyridine, were simultaneously
      assayed in triplicate by a stability-indicating high-performance liquid
      chromatographic (HPLC) method. This method was simple, sensitive (limit of
      quantitation (LOQ), 2 ng injected for both compounds), rapid (run time was 7 min)
      and precise (mean recovery was 100.5+/-2.9 and 103.6+/-1.9% for pyridine and
      ceftazidime, respectively). The ceftazidime stability in the 5% dextrose solution
      was lower than in the 0.9% sodium chloride solution. When stored at 37 degrees C
      in a disposable infusion device, the stability of the ceftazidime is included in
      large hourly range, depending strongly on the manufacturer. The stability of
      ceftazidime exceed 19 h in none studied cases. The pyridine formed in 24 h was in
      the range of 100-400 mg depending on devices and infusions.

PMID- 11836052
TI  - Influence of a polymeric formulation of ketoprofen on its diffusion into
      cerebrospinal fluid in rats.
AB  - Poly(D,L)lactide nanocapsules (NCs) have been proposed as an alternative carrier
      for many drugs. We investigated the influence of this formulation on the
      pharmacokinetics of ketoprofen in the plasma and cerebrospinal fluid (CSF). Male
      Wistar rats were given intraperitoneal dose of ketoprofen (5 mg/kg) in a
      suspension of NCs or in a carboxymethylcellulose (CMC) solution (reference
      preparation). Blood and CSF samples were collected at different times up to 24 h
      after dosing. The unbound fraction of ketoprofen in plasma (f(u)) was determined
      using ultrafiltration. The total (C(T)) and free (C(F)) concentrations of
      ketoprofen in plasma and the simultaneous CSF concentrations (C(CSF)) were
      measured by a HPLC method and the areas under the curve (AUC(T), AUC(F),
      AUC(CSF)) were calculated. AUC(T) of ketoprofen-loaded NCs in plasma was similar
      to that of the reference solution, while AUC(F) of the former (5.41 mg/l x h) was
      higher than that produced by the latter (4.03 mg/l x h). Accordingly, the unbound
      fraction (f(u)) was higher after administration of NCs than that of the solution
      (2.5 and 1.8%, respectively). Finally, AUC(CSF) were identical for both
      formulations. These findings suggest that the binding of ketoprofen to plasma
      proteins is not the major factor that governs its blood-to-CSF exchanges.

PMID- 11836053
TI  - Spectrophotometric determination of clobetasol propionate, halobetasol
      propionate, quinagolide hydrochloride, through charge transfer complexation.
AB  - Two spectrophotometric procedures are described for the determination of
      clobetasol propionate(I), halobetasol propionate(II) (corticosteroids) and
      quinagolide hydrochloride(III) (prolactin inhibitor). For corticosteroid drugs,
      the procedures are based on the formation of phenyl hydrazones of the
      corticosteroids which are subsequently subjected to charge transfer complexation
      reaction with either 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) as pi-acceptor or
      with iodine as sigma-acceptor. Prolactin inhibitor was reacted directly with the
      previous reagents. The molar ratios of the reactants were established and the
      experimental conditions were studied giving maximum absorption at 588 and 290 nm
      with DDQ and iodine methods, respectively for the three drugs. The concentration
      ranges were 20-150,50-300, and 20-80 microg ml(-1) in DDQ method for (I), (II),
      and (III), respectively and 13-20,15-40, and 8-32 microg ml(-1) in iodine method
      for (I), (II) and (III), respectively.

PMID- 11836054
TI  - Simultaneous determination of fosinopril and hydrochlorothiazide in
      pharmaceutical formulations by spectrophotometric methods.
AB  - Three new spectrophotometric procedures for the simultaneous determination of
      fosinopril and hydrochlorothiazide are described. The first method, derivative
      differential spectrophotometry, comprised of measurement of the difference
      absorptivities derivatized in the first-order (DeltaD(1)) of a tablet extract in
      0.1 N NaOH relative to that of an equimolar solution in methanol at wavelengths
      of 227.6 and 276.4 nm, respectively. The second method, depends on the
      application ratio spectra derivative spectrophotometric method to resolve the
      interferance due to spectral overlapping. The analytical signals were measured at
      237.9, 243.8 nm for fosinopril and 262.4, 269.3 and 278.6 nm for
      hydrochlorothiazide in the binary mixture, in the first derivative of the ratio
      spectra of the mixture solutions in methanol. Calibration graphs were established
      for 4.0-50.0 microg ml(-1) fosinopril and 2.0-14.0 microg ml(-1)
      hydrochlorothiazide in binary mixture. The third method, absorbance ratio method,
      the determination of fosinopril and hydrochlorothiazide was performed by using
      the absorbances read at 210.0, 219.5 and 271.7 nm in the zero-order spectra of
      their mixture. The developed methods were compared with absorbance ratio method.
      Application of the suggested procedures were successfully applied to the
      determination of this compound in synthetic mixtures and in pharmaceutical
      preparations, with high percentage of recovery, good accuracy and precision.

PMID- 11836055
TI  - Influence of physico-chemical parameters of some barbituric acid derivatives on
      their retention on an amide embedded RP silica column.
AB  - Retention parameters of 45 different barbituric acid derivatives were determined
      on an amide embedded RP silica column (Discovery RP-AmideC16) using non-buffered
      water-acetonitrile eluent systems. Linear correlation were calculated between the
      logarithm of the capacity factor and the acetonitrile concentration in the
      eluent. To determine the retention behavior of barbituric acid derivatives,
      stepwise regression analysis (SRA) and principal component analysis (PCA)
      followed by two-dimensional nonlinear and modified nonlinear mapping was used. It
      can be concluded, the retention of barbituric acid derivatives are governed
      mainly by the steric parameters of the substituents. Principal component analysis
      indicated that the barbituric acid derivatives have mixed retention on this amide
      embedded RP silica column in water-acetonitrile eluent.

PMID- 11836056
TI  - Spectrofluorimetric analysis of certain macrolide antibiotics in bulk and
      pharmaceutical formulations.
AB  - The macrolides (erythromycin, erythromycin esters, azithromycin dihydrate,
      clarithromycin and roxithromycin) can be analyzed by a simple spectrofluorimetric
      method based on the oxidation by cerium(VI) in the presence of sulphuric acid and
      monitoring the fluorescence of cerium(III) formed at lambda(ex) 255 nm and
      lambda(em) 348 nm. All variables affecting the reaction conditions as cerium(VI),
      sulphuric acid concentrations, heating time, temperature and dilution solvents
      were carefully studied. Linear calibration graphs were obtained in the range of
      42.6-1200 ng ml(-1) with a percentage relative standard deviation in the range of
      0.014-0.058%. Quantitation and detection limits were calculated. The method was
      applied successfully for the assay of the studied drugs in pure and
      pharmaceutical dosage forms as tablets, capsules and suspension. Recovery
      experiments revealed recovery of 98.3-100.8%. The effect of potential
      interference due to common ingredients as glucose, sucrose, lactose, citric acid,
      and propylene glycol was investigated. Applying standard addition method shows a
      recovery of 97.7-100.9% macrolide antibiotics from their corresponding dosage
      forms.

PMID- 11836057
TI  - Thermodynamics in [Mn(II)-antibiotics-bacitracin] mixed system: a polarographic
      approach.
AB  - Polarographic technique was used to determine the kinetic parameters,
      thermodynamic parameters and stability constants (log(beta)) of Mn(II) complexes
      with neomycin, chlortetracycline, oxytetracycline, tetracycline, penicillin V and
      penicillin G as primary ligands and bacitracin as the secondary ligand, at pH
      7.3+/-0.01 and an ionic strength mu=1.0 M (NaClO(4)) at 25 degrees C. The study
      was also carried out at 35 degrees C to determine the stability constants and
      thermodynamic parameters viz. enthalpy change (DeltaH), entropy change (DeltaS)
      and free energy change (DeltaG) of complexes.

PMID- 11836059
TI  - A rapid spectrophotometric method for the determination of mefloquine
      hydrochloride.
AB  - A simple ultraviolet spectrophotometric method for the estimation of mefloquine
      hydrochloride in methanol (ME(2)) has been developed and has been compared with
      the reported ultraviolet spectrophotometric method in 0.1 N hydrochloric acid
      (ME(1)). Analytical parameters such as stability, selectivity, accuracy and
      precision have been established for both the methods and evaluated statistically
      to assess the application of the individual methods. Both the methods were
      compared with the existing pharmacopoeial method for estimation of the drug. Both
      the methods were found to have the advantages for simplicity, stability,
      sensitivity, reproducibility and accuracy for using as an alternate to the
      existing non-spectrophotometric methods for the routine analysis of the drug in
      pharmaceutical formulations and also in pharmaceutical investigations involving
      mefloquine hydrochloride.

PMID- 11836058
TI  - Comparison of in vitro BBMEC permeability and in vivo CNS uptake by microdialysis
      sampling.
AB  - The studies presented in this report were designed to assess the correlation of
      the bovine brain microvessel endothelial cell (BBMEC) apparent permeability
      coefficient (P(app)) and in vivo BBB penetration using microdialysis sampling. A
      mathematical model was developed to describe the relationship of brain
      extracellular fluid (ECF) concentration to free drug in plasma. The compounds
      studied have a broad range of physico-chemical characteristics and have widely
      varying in vitro and in vivo permeability across the blood-brain barrier (BBB).
      BBMEC permeability coefficients vary in magnitude from a low of 0.9 x 10(-5) cm/s
      to a high value of 7.5 x 10(-5) cm/s. Corresponding in vivo measurements of BBB
      permeability are represented by clearance (CL(in)) into the brain ECF and range
      from a low of 0.023 microl/min/g to a high of 12.9 microl/min/g. While it is
      apparent that in vitro data from the BBMEC model can be predictive of the in vivo
      permeability of a compound across the BBB, there are numerous factors both prior
      to and following entry into the brain which impact the ultimate uptake of a
      compound. Even in the presence of high BBB permeability, factors such as high
      plasma protein binding, active efflux across the BBB, and metabolism within the
      CNS can greatly limit the ultimate concentrations achieved. In addition,
      concentrations in the intracellular space may not be the same as concentrations
      in the extracellular space. While these data show that the BBMEC permeability is
      predictive of the in vivo BBB permeability, the complexity of the living system
      makes prediction of brain concentrations difficult, based solely on the in vitro
      measurement.

PMID- 11836060
TI  - The investigation and the use of high flow column-switching LC/MS/MS as a high
      throughput approach for direct plasma sample analysis of single and multiple
      components in pharmacokinetic studies.
AB  - Recently direct plasma injection LC/MS/MS technique has been increasingly used in
      pharmaceutical research and development due to the demand for higher throughput
      of sample analyses. In this work, two on-line extraction methods including high
      flow LC/MS/MS and high flow column switching LC/MS/MS were investigated. The
      evaluations were conducted and focused on their performances with respect to peak
      responses, separation efficiency, and signal to-noise ratio in a multiple
      component LC/MS/MS assay. Two HPLC pumps were used-with one for high flow
      delivery and one for gradient elution. A CTC autosampler was used to inject
      plasma samples. High flow LC was achieved by the use of 4 ml/min flow rate on a 1
      x 50 mm Waters Oasis column. A 2 x 100 mm YMC column was coupled via a column
      switching valve. The extracted analytes were analyzed in multiple-reaction
      monitoring (MRM) mode using a triple quadrupole MS/MS. As a rapid and simple
      procedure, vortex-mixing plasma and internal standard directly in sample vials
      completed sample preparation. The high flow column switching method (two-column
      system) provided sharper peak shape than the conventional high flow method. This
      effect increased analyte signal-to-noise ratio and sensitivity. Narrower peak
      width resulted in much better separation efficiency, which was required for
      multiple compound (N-in-1) analysis. A 2 mm I.D. column resulted in better peak
      shape and resolution than using a smaller I.D. column. The selected method
      achieved acceptable recoveries for most of the compounds tested, and it was
      successfully applied to a 10-in-1 pharmacokinetic (PK) study. The results showed
      that the dynamic range, lower limit of quantitation, assay accuracy and precision
      were acceptable for all compounds. Rapid sample preparation eliminated labor
      intensive and time consuming processes and improved productivity. This high
      throughput on-line extraction high flow column switching method has been proven
      particularly useful for multiple component analysis in PK studies.

PMID- 11836061
TI  - Determination of relative UV response factors for HPLC by use of a
      chemiluminescent nitrogen-specific detector.
AB  - Ultraviolet (UV) absorbance is the most widely used detection method for high
      performance liquid chromatography (HPLC) separations. In pharmaceutical analysis,
      purity determinations often include quantitation of related impurities based on
      relative HPLC peak areas obtained at a specific wavelength. In order for this
      quantitation to accurately reflect weight percentages of impurities, the relative
      UV response factors (absorptivities) at the given wavelength must be known. In
      this work, we present a convenient method for determining relative UV response
      factors on-line, without isolation or purification of impurities, without
      standards, and without requiring known analyte concentrations. The procedure
      described makes use of a chemiluminescent nitrogen-specific HPLC detector (CLND)
      in conjunction with a UV detector. The CLND response is directly proportional to
      the number of moles of nitrogen in each eluting peak, and can, therefore, be used
      to determine relative amounts of each nitrogen-containing impurity present in the
      sample, provided the molecular formulas are known (e.g. from exact mass LC-MS).
      It is a simple matter, then, to determine the relative UV response factors from
      the UV area ratios obtained for the same sample. The feasibility and accuracy of
      this method is demonstrated for gradient HPLC separations of commercially
      available compounds of widely varying structures. Finally, the method's utility
      in obtaining accurate mass balance is demonstrated by application to
      photodegradation of nifedipine.

PMID- 11836062
TI  - The use of the Box-Behnken experimental design in the optimisation and robustness
      testing of a capillary electrophoresis method for the analysis of ethambutol
      hydrochloride in a pharmaceutical formulation.
AB  - Box-Behnken experimental designs do not appear to be extensively used in
      optimisation of analytical methods using capillary electrophoresis (CE). This
      paper describes the use of the Box-Behnken experimental design to optimise the
      factors affecting the separation of ethambutol hydrochloride (EB), its impurity 2
      amino-1-butanol and the internal standard (phenylephrine hydrochloride) in a CE
      method for a pharmaceutical tablet assay. The three factors studied
      simultaneously were: buffer pH, buffer concentration and applied electric field,
      each at three levels. The method was optimised with respect to three responses:
      resolution between peaks, theoretical plate count and the migration time of the
      EB peak. A statistical programme, which applies a multiple response optimisation
      algorithm, was used to calculate and optimise the three responses simultaneously.
      The optimum conditions were established to be 58.0 mM sodium borate buffer at pH
      9.50 and an applied electric field of 412 V/cm. The robustness of the method was
      also determined and confirmed using a second Box-Behnken design, as part of the
      validation exercise. System suitability values for the method were derived from
      the regression surface analysis. The CE method for a pharmaceutical tablet
      formulation was further validated according to current regulatory requirements,
      with respect to linearity and range, precision, specificity, accuracy and limit
      of quantitation. The optimised method gives a fast and efficient separation under
      4 min, with complete resolution between the three peaks, and represents an
      improvement over the existing USP method. It can be concluded that the Box
      Behnken experimental design provides a suitable means of optimising and testing
      the robustness of a CE pharmaceutical method.

PMID- 11836063
TI  - LC determination of the anti-ulcer agent CDRI-85/92 in rat serum.
AB  - CDRI-85/92 is a new potent anti-ulcer compound developed by Central Drug Research
      Institute, Lucknow (India). This compound is in advanced stage of preclinical
      trials. A High-performance liquid chromatographic (HPLC) method was developed and
      validated for the analysis of CDRI-85/92 using rat serum. The HPLC analysis,
      applicable to 0.5-ml volumes of serum, involved protein precipitation of serum
      samples with acetonitrile (1:3 v/v) followed by centrifugation and separation on
      a C-18 column and the use of UV detector at the wavelength 250 nm. The method was
      sensitive with a lowest limit of quantitation (LLOQ) of 1.25 ng ml(-1) in rat
      serum and the recovery was more than 96%. The linearity was satisfactory as
      indicated by correlation of >0.99, in addition to the visual examination of the
      calibration curves. The precision and accuracy were acceptable as indicated by
      relative standard deviation (R.S.D.) ranging from 4.15 to 8.21%, bias values
      ranging from 2.96 to 11.18%. In-process stability evaluation showed the stability
      of the compound in processed samples lasted up to 168 h. The method was applied
      for analysing CDRI-85/92 in rat serum after administration of single oral or iv
      bolus dose of 20 mg kg(-1). The robustness/ruggedness of the HPLC procedure was
      tested using different HPLC instrumentation and column of different make. The
      assay was found to be sensitive (limit of quantification was 1.25 ng ml(-1)),
      specific (retention time for CDRI-85/92 is 7.5 min), accurate (% bias is <12%),
      precise (% R.S.D. is <10%), robust (no significant change in peak profile in two
      HPLC Instruments) and reliable for use in pharmacokinetic or toxicokinetic
      studies.

PMID- 11836064
TI  - Oxidation of adrenaline and noradrenaline by solved molecular oxygen in a FIA
      assembly.
AB  - A simple and effective procedure is proposed for the study and simultaneous
      determination of adrenaline and noradrenaline. The fluorimetric determination of
      both substances is performed in a flow injection assembly and by oxidation of
      both drugs with the solved molecular oxygen. The influence of different
      parameters is empirically studied and the interpretation of the reaction
      mechanism is also added. The determination of adrenaline is monitored at 450 nm
      and the outputs at 520 nm correspond to the adrenaline and noradrenaline global
      amount; for both lectures lambda(exc) 329 nm. The influence of temperature is
      relevant and analytical determination occurred at 55 degrees C by immersing the
      sample loop in a water bath. The linear range for adrenaline is over 0.5-20
      microg ml(-1), limit of detection for both compounds is 0.2 microg ml(-1): the
      influence of foreign compounds as potential interferents is also tested; and,
      finally the procedure is applied to determination of both chatecolamines in
      synthetic samples.

PMID- 11836065
TI  - Simultaneous dissolution profiles of two drugs in pharmaceutical formulations by
      an FIA manifold.
AB  - This article deals with the simultaneous determination of dissolution profiles of
      two drugs with overlapped spectra, present in the same pharmaceutical
      formulation. The official procedure for the dissolution profile is adapted to the
      continuous-flow methodology; the dissolution vessel is connected to an FIA
      manifold, in which the sample aliquots from the dissolution vessel are treated in
      order to adjust to the suitable pH and dilution degree to be monitored. The
      resulting solution is injected into the carrier stream, an acetic acid-acetate
      buffer at pH 4.3 and forced to the flow-cell of the spectrophotometer. The
      simultaneous determination of both profiles is based on the first derivative
      spectra and the zero-crossing mathematical procedure. The empirical profile of
      the curve is adjusted by regression using different approaches; the three
      parameter plot method is selected. The analytical errors, when the concentration
      of one drug is very low or very high, are also checked. A binary mixture in
      commercially available formulations of solid oral administration of
      sulphametoxazole and trimethoprim is presented.

PMID- 11836066
TI  - Effects on brain and behavior caused by developmental exposure to endocrine
      disrupters with estrogenic effects.

PMID- 11836067
TI  - Neurobehavioral effects of dietary soy phytoestrogens.
AB  - Phytoestrogens, plant-derived nonsteroidal estrogens found in high abundance in
      most soy food products, have been studied for their potential beneficial effects
      against hormone-dependent cancers and age-related diseases. However, little is
      known about the influence of phytoestrogens on the brain or behavior. This brief
      review describes mainly our own studies in rodents that have examined the
      influence of dietary soy isoflavones on certain aspects of brain structure,
      learning, memory and anxiety along with the brain androgen-metabolizing enzyme,
      aromatase. These studies used a commercially available diet rich in
      phytoestrogens (Phyto-rich) vs. a custom diet relatively free of phytoestrogens
      (Phyto-free). The phytoestrogen content of each diet was determined by high
      performance liquid chromatography analysis, circulating plasma phytoestrogen
      levels were quantified by gas chromatography mass spectroscopy and concentrations
      of phytoestrogens in specific brain regions were measured by time-resolved
      fluoroimmunoassay (TR-FIA). Our studies showed that brain aromatase levels were
      not significantly altered by phytoestrogen diet treatments in perinatal, maternal
      or adult rats. However, volumes of the sexually dimorphic nucleus of the preoptic
      area (SDN-POA) were significantly affected by the Phyto-free diet treatment in
      male rats during adulthood, where SDN-POA volumes were smaller compared to Phyto
      rich male values. Additionally, the Phyto-rich diet fed to adult male and female
      rats produced anxiolytic effects as assessed in the elevated plus maze vs. Phyto
      free fed animals. Finally, when learning and memory parameters were examined in a
      radial arm maze testing visual-spatial memory (VSM), the diet treatments
      significantly changed the typical sexually dimorphic pattern of VSM.
      Specifically, adult Phyto-rich fed females outperformed Phyto-free fed females,
      while in males on the same diets, the opposite pattern of maze performance was
      observed. When female vs. male performance was compared, Phyto-rich females
      executed the VSM task in a manner similar to that of Phyto-free fed males, while
      Phyto-free fed female's VSM was comparable to Phyto-rich males. These results
      indicate that consumption of dietary phytoestrogens resulting in very high plasma
      isoflavone levels (in many cases over a relatively short interval of consumption
      in adulthood) can significantly alter sexually dimorphic brain regions, anxiety,
      learning and memory. The findings of these studies identify the biological
      actions of phytoestrogens, specifically isoflavones and their metabolites, found
      in animal soy-containing diets on brain and behavior and implicate the importance
      of phytoestrogens given the recognized significance of estrogens in brain and
      neural disorders, such as Alzheimer's disease, especially in women.

PMID- 11836068
TI  - Reproductive consequences of EDCs in birds: what do laboratory effects mean in
      field species?
AB  - The varied reproductive strategies of birds present a challenge in developing
      reliable indices for the assessment of effects of endocrine disrupting chemicals
      (EDCs). Precocial species, such as quail, appear to be most sensitive to EDC
      effects during embryonic development. Although the Japanese quail (Coturnix
      japonica) is a nonnative lab species, its reproductive strategy is similar to
      that of many free-ranging species. Because a great deal is known about the
      reproductive biology of this species and Japanese quail have a short generation
      time, this species is an ideal candidate for testing EDC effects. In this review,
      we present data collected in a two-generation design with embryonic exposure to
      estradiol benzoate (EB). This study was conducted to provide fundamental
      information for establishing reliable reproductive endpoints associated with
      estrogenic EDC exposure. Data were collected for a variety of endpoints, which
      were chosen as measures of reproductive capability and success. These
      reproductive fitness measures included fertility, hatching success, and offspring
      viability. Endocrine measures consisted of plasma hormone levels and gonad
      weight/condition. Neuroendocrine systems, such as the monoamine neurotransmitter
      systems, regulate hypothalamic gonadotropin releasing hormone (GnRH) and
      reproductive behavior. Therefore, these variables should potentially be very
      sensitive indicators. Behavioral measures included reproductive behavior. Results
      showed that embryonic estradiol exposure affected endocrine and behavioral
      responses in males and impacted productivity in females. Therefore, quails
      provide an excellent model to determine fundamental actions of EDCs. The
      laboratory trials then serve as a basis for the extrapolation of findings of
      controlled laboratory studies to effects that may be observable in free-ranging
      species.

PMID- 11836069
TI  - Altered behaviors in male mice, male quail, and salamander larvae following early
      exposures to the estrogenic pesticide methoxychlor.
AB  - Numerous publications show that methoxychlor (MXC), in use today as a DDT
      substitute, is a reproductive toxicant; it produces deleterious effects on the
      structure and function of the reproductive organs in exposed species. Exposure of
      mice (33 mg/kg body weight) to purified (95%) MXC at the time of implantation, or
      injection, of 5 mg MXC into freshly laid quail eggs prior to artificial
      incubation, altered sexual arousal and sexual behavior in adult males of both
      species. When placed near a plastic partition with an estrus female behind it,
      the MXC-exposed male mice showed no sexual arousal, spent less time near the
      partition, and exhibited lower testosterone levels. Similarly, adult quail males
      that were exposed to MXC during incubation showed a lack of sexual interest and
      copulatory behavior when presented with a receptive female. Some males showed a
      longer latency period before mounting the female, while others did not show any
      sexual interest at all. Exposure of salamander embryos to purified MXC at or
      above 0.3 microM (0.1 mg/l) induced precocial hatching of embryos and reduced the
      startle response and the distance traveled in response to startle. Exposing
      hatched larvae to MXC for 3 days also resulted in a blunted startle response. Due
      to the blunted startle response and decreased avoidance travel, the exposed
      salamander larvae appear more susceptible to predation and these effects may
      contribute to amphibian population declines. The results of these studies
      indicate that developmental exposures to environmental chemicals with hormonal
      activities produce undesirable behaviors that may affect population dynamics and
      survivability of exposed species.

PMID- 11836070
TI  - Effects of lifelong dietary exposure to genistein or nonylphenol on amphetamine
      stimulated striatal dopamine release in male and female rats.
AB  - Estrogen modulates baseline and amphetamine-stimulated dopamine (DA) release in
      the adult female rat striatum. The isoflavone found in soybeans, genistein, is a
      phytoestrogen and may have comparable effects on striatal DA levels. Similarly,
      the industrial intermediate and potential endocrine disrupter, para-nonylphenol,
      has estrogen-like effects. Here, Sprague-Dawley rats were continuously exposed to
      phytoestrogen-free diets containing 0, 100, or 500 ppm genistein (Experiment 1)
      or 0 or 200, or 750 ppm nonylphenol (Experiment 2) beginning at conception and
      continuing throughout. To eliminate estrous cycle influences on DA levels,
      females were ovariectomized at adulthood. As adults, striatal levels of DA and
      its metabolites [3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid
      (HVA)] were measured in unanesthetized male and female rats via cerebral
      microdialysis before and for 200 min after an intraperitoneal injection of 2
      mg/kg D-amphetamine. Although baseline 5-hydroxyindoleacetic acid (5-HIAA) levels
      indicated an isolated effect in genistein-treated females, there were no
      meaningful differences among treatment groups in baseline levels of DA, DOPAC, or
      HVA. However, dietary exposure to 500 ppm genistein significantly potentiated
      amphetamine-stimulated DA release in males and a similar trend was apparent, but
      not statistically significant, in females. Dietary exposure to 200 or 750 ppm
      nonylphenol had no significant effects in males or females. These results suggest
      that dietary genistein exposure may act similarly to estradiol in augmenting
      amphetamine-stimulated DA release.

PMID- 11836071
TI  - Neurobehavioral actions of coumestrol and related isoflavonoids in rodents.
AB  - Isoflavonoids are plant estrogens that are increasingly advocated as a natural
      alternative to estrogen replacement therapy (ERT) and are available as dietary
      supplements. As weak estrogen agonists/antagonists with a range of other
      enzymatic activities, the isoflavonoids provide a useful model for the actions of
      endocrine disruptors. This paper reviews the responses of rodents to diets
      containing coumestrol or an isoflavone supplement in comparison to animals fed
      the phytoestrogen-free AIN76A diet. Neural mechanisms were investigated by
      examining isoflavonoid effects on ER(alpha)-dependent (regulation of oxytocin
      receptor [OTR] binding in the ventromedial nucleus of the hypothalamus [VMN]) and
      ERbeta-dependent (regulation of ERbeta mRNA in the paraventricular nucleus [PVN])
      endpoints. Activational as well as organizational effects on sexual behavior and
      gonadotropin secretion were observed for coumestrol. Treatment of rat dams with a
      100-ppm coumestrol diet from birth to postnatal day (PND) 21 induced premature
      anovulation in female offspring, and treatment from birth to PND 10 suppressed
      sexual behavior in male offspring. One-week treatment of ovariectomized (OVX)
      female rats with the same coumestrol diet increased ERbeta mRNA expression in the
      PVN, an effect opposite to that of estradiol. Ten days of treatment with a 200
      ppm coumestrol diet increased LH secretion in OVX wild-type mice, an effect
      opposite to the normal negative feedback effects of estradiol. No effects were
      observed in ER(alpha) knockout (ER(alpha)KO)-OVX females, indicating that
      coumestrol's action on LH was mediated through ER(alpha). Similar activational
      effects were observed for the isoflavone diet. The lordotic response to estrogen
      was significantly reduced by 2 days of treatment of OVX adult females with an
      isoflavone diet providing 13 ppm genistein and 33 ppm daidzein. One week of
      treatment with the same isoflavone diet produced an effect opposite to that of
      estradiol in the PVN, increasing ERbeta mRNA expression above control levels.
      These investigations show that, in spite of their preferential affinity for
      ERbeta, isoflavonoids act through both ER(alpha) and ERbeta. Moreover, their
      neurobehavioral actions were antiestrogenic, either antagonizing or producing an
      action in opposition to that of estradiol. This work demonstrates that even
      small, physiologically relevant exposure levels can alter estrogen-dependent gene
      expression in the brain and complex behavior.

PMID- 11836072
TI  - Ethological methods to study the effects of maternal exposure to estrogenic
      endocrine disrupters: a study with methoxychlor.
AB  - There has been increasing interest, both at the scientific and regulatory level,
      in the use of ethological methods for evaluating neural effects of endocrine
      disrupters. We present a series of ethological studies on the effects of maternal
      exposure to low, environmentally relevant doses (0.02, 0.2, and 2 microg/g mother
      bw/day) of the estrogenic pesticide methoxychlor (MXC) on behavior. From
      gestation day 11 to 17, female mice spontaneously drank oil with or without MXC;
      their maternal behavior was examined from postpartum days 2 to 15. MXC treatment
      during pregnancy produced slight changes in the expression of maternal behavior:
      females fed the lower MXC dose spent less time nursing the pups as compared to
      control dams. Their maternally exposed offspring were subjected to a series of
      behavioral tests at different ages. Maternal exposure to MXC affected behavioral
      responses to novelty in both sexes at periadolescence. The onset of male intrasex
      aggression was delayed in males prenatally exposed to low doses of MXC, since
      exposed males showed low levels of aggressive interactions during early
      adolescence but not after they reached adulthood. When adults, MXC-exposed
      females, but not males showed increased exploration in an unfamiliar open-field.
      While a sex difference was observed in the control group, with males being
      significantly more active in the open field than females, prenatal treatment with
      some MXC doses tended to decrease the sexual dimorphism in activity levels in the
      novel environment. Ethology, as the evolutionary study of behavior, may provide a
      framework for integrating a functional perspective (i.e., evolutionary
      significance) to studies on proximate mechanisms that can account for behavioral
      alterations induced by developmental exposure to endocrine disrupters.

PMID- 11836073
TI  - Endocrine disruption caused by two common pollutants at "acceptable"
      concentrations.
AB  - This report focuses on the impact of low concentrations of two purported
      endocrine-disrupting xenobiotic compounds, nonylphenol and methoxychlor, on two
      freshwater teleosts of the genus Xiphophorus, X. maculatus, commonly known as the
      platyfish, and X. helleri, commonly known as the swordtail. Nonylphenol exposure
      increased mortality rates, elicited stress behaviors, decreased body weight and
      significantly hampered gonadal development and reproductive function.
      Methoxychlor exposure elicited stress behaviors, decreased body weight and
      significantly retarded sexual development. This report demonstrates that, even at
      "acceptable" concentrations, these compounds pose a serious threat to our aquatic
      ecosystems.

PMID- 11836074
TI  - Quantitative three-dimensional reconstruction: feasibility for studies of
      sexually dimorphic hypothalamic development in rats.
AB  - The adult rat brain develops through an interplay of neuronal proliferation with
      programmed cell death. Sensory stimulation, as well as growth factors and
      steroids, may alter the balance between these competing processes. "Endocrine
      disrupters" (EDs) may do the same by mimicry or modulation of endogenous
      hormones. The sexually dimorphic nucleus (SDN) of the medial preoptic
      hypothalamus contains a high concentration of estrogen receptors (ERs). The SDN
      develops to a final adult volume, which may be used as an indication of the
      hormonal conditions during perinatal development. Although male rats have been
      repeatedly observed to have a greater adult SDN volume than female rats,
      variability between the actual measurements reported (both within and between
      laboratories) have been rather large. Exposure of female rats to testosterone (or
      excessive estradiol, beyond the binding capacity of alpha-fetoprotein) has been
      shown to masculinize them through a P450 aromatase that converts testosterone to
      estrogen in the SDN. Exposure of males to estradiol may feminize them at low
      doses through interference with the synthesis of their endogenous testosterone,
      which normally acts on SDN ERs following aromatization. We have employed computer
      assisted reconstruction methods in order to render the SDN within the surrounding
      hypothalamus in 3-D for computation of its volume. Ongoing studies are
      investigating whether exposure through the diet to estrogenic endocrine
      disruptors such as genistein, nonylphenol, and ethinyl estradiol might produce
      effects similar to those of estradiol itself on the adult SDN.

PMID- 11836075
TI  - Cognitive testing (delayed non-match to sample) during oral treatment of female
      adolescent monkeys with the estrogenic pesticide methoxychlor.
AB  - This report presents preliminary data from a study of endocrine disruption in
      adolescence. A delayed non-match to sample (DNMS) task was used to assess the
      effects of the endocrine-active agent methoxychlor (MXC; 0, 25, or 50 mg/kg/day
      oral administration) in adolescent female monkeys 24-36 months of age (n=7
      8/group). The testing utilized an automated touchscreen operant system (Cambridge
      Neuropsychological Test Automated Batteries [CANTAB]) with abstract, trial-unique
      visual stimuli. Basic performance of the task was established prior to dosing,
      training with simultaneous presentation of sample and choice stimuli continued
      during dosing, and delays (1/2, 1 or 2 s) were introduced near the end of the
      dosing period. The MXC50 group performed more poorly than controls during delay
      testing at the end of the dosing period, as well early in training with
      simultaneous presentation. No interaction between treatment group and delay
      interval was found. No significant differences from controls were observed at the
      lower dose (MXC25). Thus, MXC at a daily dose of 50 mg/kg appeared to interfere
      in a general way with performance of this visual discrimination and memory task.
      Further investigation will be needed to identify the impairment leading to this
      performance deficit.

PMID- 11836076
TI  - Telemedicine in Europe.

PMID- 11836077
TI  - Internal medicine -- back to the future of health care delivery.

PMID- 11836078
TI  - Hyponatremia in acute brain disease: the cerebral salt wasting syndrome.
AB  - Hyponatremia in acute brain disease is a common occurrence, especially after an
      aneurysmal subarachnoid hemorrhage. Originally, excessive natriuresis, called
      cerebral salt wasting, and later the syndrome of inappropriate antidiuretic
      hormone secretion (SIADH), were considered to be the causes of hyponatremia. In
      recent years, it has become clear that most of these patients are volume-depleted
      and have a negative sodium balance, consistent with the original description of
      cerebral salt wasting. Elevated plasma concentrations of atrial or brain
      natriuretic peptide have been identified as the putative natriuretic factor.
      Hyponatremia and volume depletion may aggravate neurological symptoms, and timely
      treatment with adequate replacement of water and NaCl is essential. The use of
      fludrocortisone to increase sodium reabsorption by the renal tubules may be an
      alternative approach.

PMID- 11836079
TI  - Diabetes mellitus and cardiovascular disease.
AB  - Diabetes is associated with a high incidence and poor prognosis of cardiovascular
      disease, and with high short- and long-term mortality. Adequate treatment of
      cardiovascular disorders and aggressive management of coexisting risk factors
      have proved to be at least as effective in diabetic as in nondiabetic patients in
      randomized, controlled studies. Indeed, treating diabetic patients with
      cardiovascular disease results in a larger absolute risk reduction than in
      nondiabetic subjects. Nevertheless, diabetic patients often receive inadequate
      therapy, which may, to a certain extent, explain their poor prognosis.
      Recommendations for the treatment of diabetic patients with acute myocardial
      infarction should include beta-blockers, aspirin, and ACE-inhibitors in all
      patients in whom no specific contraindications exist. Fibrinolysis should be
      administered when indicated, and the benefits of improving glycemic control
      should not be forgotten either. In patients with multi-vessel disease who need
      revascularization, when selecting the type of procedure, the superiority of
      surgical revascularization over angioplasty should be borne in mind. Even heart
      transplantation should be included as a therapeutic option since there are no
      data to support the exclusion of patients on account of their diabetes. Finally,
      coexisting risk factors should be intensively treated through lifestyle
      intervention, with or without drug therapy, in order to achieve secondary
      prevention goals.

PMID- 11836080
TI  - The impact of resistance to methicillin in Staphylococcus aureus bacteremia on
      mortality.
AB  - Background: It is unclear whether methicillin-resistant Staphylococcus aureus
      (MRSA) and methicillin-sensitive S. aureus (MSSA) differ in virulence. We
      therefore carried out a prospective study of cases of S. aureus bacteremia over a
      period of 2 years at our university hospital. We report herein the results of a
      comparative analysis of the clinical characteristics and mortality rates
      associated with cases of bacteremia caused by MRSA and MSSA. Methods: Over a 2
      year period, we reviewed the medical records of hospitalized patients with blood
      cultures positive for S. aureus. Demographic characteristics, underlying
      diseases, diagnosis, clinical features, severity, laboratory findings,
      antimicrobial treatment, and resistance to methicillin were analyzed as possible
      risk factors for death attributed to bacteremia. Results: The rate of mortality
      attributed to bacteremia was 27.3% (27 patients): 13 (43.3%) deaths were recorded
      for patients infected with MRSA and 14 (20.3%) for patients infected with MSSA
      (P=0.0339, OR=3.00 (1.08--8.46)). Two variables were significantly associated
      with death within 14 days of the onset of bacteremia in univariate and
      multivariate analyses after adjusting for antimicrobial treatment: malignant
      hematologic disease (protective factor; OR=0.184 (0.038--0.882)) and resistance
      to methicillin (risk factor; OR=2.97 (1.12--7.88)). Conclusion: This study shows
      that S. aureus bacteremia has a high mortality rate, especially if the strain
      involved is methicillin-resistant, regardless of patient age and the efficacy of
      antimicrobial treatment.

PMID- 11836081
TI  - Apolipoprotein E and colon cancer. Expression in normal and malignant human
      intestine and effect on cultured human colonic adenocarcinoma cells.
AB  - Background: Apolipoprotein E (apo E) is a key regulatory protein in lipoprotein
      metabolism and it is also a potent inhibitor of cell proliferation. Although
      genetic alterations of apo E affect enterohepatic cholesterol transport and,
      presumably, the risk of colon carcinoma, the expression and potential functions
      of apo E in the human intestine are poorly known. Methods: The localization of
      apo E in normal and malignant gastrointestinal tract was studied using
      immunohistochemistry and in situ hybridization. The effect of apo E3 on cell
      polarity and the distribution of beta-catenin was examined in HT29 human colon
      adenocarcinoma cell lines. Results: Both apo E protein and mRNA were present
      throughout human intestine. The macrophages in the superficial lamina propria of
      normal colon were more strongly positive for apo E than those in the small
      intestine, where the most positively stained cells were dendritic cells and
      macrophages in the germinal centers of lymphoid follicles. In carcinomas,
      intensely positive macrophages surrounded the tumor area. In cultured
      undifferentiated HT29 cells, treatment with apo E improved cell polarity and
      translocated beta-catenin from the cytoplasm to cell--cell adhesion sites.
      Conclusions: Mononuclear phagocytes and endocrine cells are the main source of
      apo E in the gastrointestinal tract. We hypothesize that macrophage-derived apo E
      may modulate epithelial integrity and thus contribute to cell growth.

PMID- 11836082
TI  - Cardiovascular risk factors in patients discharged from departments of internal
      medicine---the Italian FADOI-2 study.
AB  - Background: The goal of this study was to describe mean levels, distribution, and
      treatment of cardiovascular risk factors among patients admitted to departments
      of internal medicine. Methods: Clinical records were obtained from patients
      discharged during the last week of October 1999 in 345 departments of internal
      medicine in Italy. A number of cardiovascular risk factors, diagnoses, and
      personal characteristics were analyzed in a total of 7476 patients aged 35 years
      or older. Not all of these personal characteristics were available for each
      patient. Results: In general, the levels of cardiovascular risk factors present
      in patients were high, with hypertension and diabetes the most frequently
      encountered. The risk of coronary heart disease (CHD) over 10 years was estimated
      using an Italian algorithm that provided high probability levels, mainly among
      cardiovascular patients (410 per 1000 in 10 years on average in both genders).
      Overall, 55% of the men and 50% of the women had levels above 200 per 1000 in 10
      years, corresponding to the conventional threshold for intensive individual
      intervention on risk factors. At discharge, about 70% of hypertensive patients
      were being treated for their condition, while the same was true of only 25% of
      dyslipidemic patients. Conclusions: Although data are incomplete, the coronary
      risk profile of patients admitted to departments of internal medicine suggests a
      high probability of future events. Treatment of risk factors amenable to
      effective action is still far from optimal, especially in the area of elevated
      blood lipids.

PMID- 11836083
TI  - Quality of life after stem cell transplantation: a patient, partner and physician
      perspective.
AB  - Background: Although increasing data are available on quality of life (QOL)
      issues after stem cell transplantation (SCT), many issues are still unresolved.
      With the increasing use of transplants in non-curative situations, quality of
      life issues have become especially important. Methods: All patients who had
      undergone SCT and had no recurrent disease were asked to provide quality of life
      data using the EORTC QLQ-C30 questionnaire at about 2.5 (n=52) and 4.5 years
      (n=33) after transplantation. In addition, the patients' partners and physicians
      were asked to estimate the patients' quality of life. Results: Scores on the
      functional scales ranged from 65 to 80 and were comparable initially and at the
      23-month follow-up. The initial, overall quality of life of the patients was 75.
      After an additional 23-month follow-up, the overall quality of life was 73.
      Fatigue, sleeping disturbances, and financial problems scored relatively high.
      Generally, in contrast to partners, physicians underestimated symptoms and
      overestimated functions and quality of life significantly. Conclusions: We
      conclude that SCT has a long-term impact on such quality of life issues as
      fatigue, sleep disturbances, dyspnea, and financial problems. Physicians tend to
      overestimate quality of life in their patients. With the increasing numbers of
      patients undergoing transplantation, more attention should be focussed on these
      issues.

PMID- 11836084
TI  - Cardiovascular drug utilization and its determinants in unselected medical
      patients with ischemic heart disease.
AB  - Background: In patients with ischemic heart disease (IHD), secondary preventive
      drug therapy improves overall prognosis. Therefore, this study evaluated
      cardiovascular drug utilization in patients suffering from IHD, identified
      factors influencing drug utilization, and determined the prevalence of shortfalls
      of antithrombotic, beta-blocker, and lipid-lowering drug use. Methods: This study
      is based on data recorded prospectively between 1996 and 1998 in two Swiss
      teaching hospitals for the SAS/CHDM pharmacoepidemiologic database project. Drug
      utilization was evaluated in all 987 monitored medical inpatients with IHD.
      Results: At discharge, only 64% of patients with IHD received platelet
      aggregation inhibitors, 42% beta-blockers, and 26% lipid-lowering drugs.
      Secondary preventive drugs were more frequently administered to patients with
      acute myocardial infarction and less frequently in the elderly. After including
      other co-factors, no gender difference could be detected. Shortfalls of
      antithrombotic therapy occurred in 6.5--8.3% of patients and shortfalls in beta
      blocker use in 9.9--23.3%. Only about half of all patients with IHD and elevated
      cholesterol received lipid-lowering drugs. Conclusions: Drugs for secondary
      prevention are prescribed to the majority of patients with IHD. However, their
      use could be further increased, especially in the elderly and in patients with
      IHD who are admitted to the hospital for reasons other than acute myocardial
      infarction. Lipid-lowering drugs should also be prescribed more often for
      patients with hypercholesterolemia.

PMID- 11836085
TI  - Rapid efficacy of highly active antiretroviral therapy in a case of HIV myelitis.
AB  - An HIV-seropositive patient with severe immunodepression was diagnosed as having
      HIV myelitis. Plasma and cerebrospinal fluid (CSF) HIV-RNA PCR were,
      respectively, 4.11 and 5.19log(10). After 1 month of treatment with highly active
      antiretroviral therapy (HAART), there was clinical recovery and both plasma and
      CSF HIV viral load had decreased considerably. This dramatic improvement was
      associated with a high concentration of antiviral drugs in the CSF, suggestive of
      the direct efficacy of HAART on HIV myelitis.

PMID- 11836086
TI  - Osteomalacia cured by surgery.
AB  - Oncogenic osteomalacia is an uncommon syndrome characterized by bone pain,
      proximal muscle weakness, hypophosphatemia, hyperphosphaturia, and a low
      concentration of 1,25-dihydroxyvitamin D. This syndrome is induced by a tumor,
      usually benign, of mesenchymal origin and resolves after its excision. We report
      a case of an oncogenic osteomalacia caused by a small mesenchymal tumor of the
      tendon sheath of the foot, a localized form of tenosynovial giant cell tumor.

PMID- 11836087
TI  - Ratio of serum vascular endothelial growth factor to platelet count correlates
      with disease activity in a patient with POEMS syndrome.
AB  - Vascular endothelial growth factor (VEGF) is known to be involved in the
      pathogenesis of POEMS (polyneuropathy, organomegaly, endocrine disorder, M
      protein, and skin lesion) syndrome. Because platelets have recently been
      recognized as transporters of VEGF, enhanced blood coagulation activity in this
      syndrome may accelerate vasopermeability by releasing VEGF from platelets in
      vivo. Here we report a case of POEMS syndrome with anasarca showing a high ratio
      of serum VEGF to platelet count, indicative of massive VEGF release from
      aggregated platelets in vivo. Changes in the ratio clearly reflected disease
      activity. This observation suggests that the ratio of serum VEGF to platelet
      count is more precise in monitoring disease activity than serum VEGF alone, and
      that VEGF released in vivo is critically involved in the pathogenesis of POEMS
      syndrome, causing hypervasopermeability.

PMID- 11836088
TI  - Chloroquine hypersensitivity syndrome.
AB  - Chloroquine is widely used for antimalarial prophylaxis. We report the first case
      of delayed hypersensitivity syndrome associated with fever, digestive symptoms,
      bullous eruption, and eosinophilia due to chloroquine as proven by drug history
      and a positive patch-test for chloroquine.

PMID- 11836089
TI  - Chemical approaches to the investigation of cellular systems.
AB  - Biochemistry in the context of a living cell or organism is complicated by many
      variables such as supramolecular organization, cytoplasmic viscosity, and
      substrate heterogeneity. While these variables are easily excluded or avoided in
      reconstituted systems, they must be dealt with in cellular environments. New
      developments have allowed researchers to begin probing the inner workings of the
      cell to gain new insight into cell function and metabolism. Advances in cellular
      imaging and in small molecule-controlled gene expression, signal transduction and
      cell surface modification are discussed in this review. These techniques have
      permitted the study of molecular components within the context of living cells.

PMID- 11836090
TI  - DNA analogues: from supramolecular principles to biological properties.
AB  - Mainly driven by the needs of antisense research, a large number of
      oligonucleotide analogues have been prepared and evaluated over the last 15
      years. Besides minor structural modifications of the building blocks of DNA and
      RNA itself, a considerable effort has been devoted to the de novo design of
      nucleoside analogues with improved binding properties. A particularly successful
      concept turned out to be that of conformational restriction. This review focuses
      on recent advances in this area and tries to summarize scope and limitations of
      this design principle.

PMID- 11836091
TI  - Histidine kinases as targets for new antimicrobial agents.
AB  - The emergence and spread of hospital acquired multi drug resistant bacteria
      present a need for new antibiotics with innovative mode of action. Advances in
      molecular microbiology and genomics have led to the identification of numerous
      bacterial genes coding for proteins that could potentially serve as targets for
      antibacterial compounds. Histidine kinase promoted two-component systems are
      extremely common in bacteria and play an important role in essential signal
      transduction for adapting to bacterial stress. Since signal transduction in
      mammals occurs by a different mechanism, inhibition of histidine kinases could be
      a potential target for antimicrobial agents. This review will summarize our
      current knowledge of the structure and function of histidine kinase and the
      development of antibiotics with a new mode of action: targeting histidine kinase
      promoted signal transduction and its subsequent regulation of gene expression
      system.

PMID- 11836092
TI  - Chloropyrimidines as a new class of antimicrobial agents.
AB  - In the course of our investigations of pyrimidines as antimycotic agents, we have
      identified a sub-class, with significant in vitro activity against mycobacteria.
      The salient feature of these pyrimidine derivatives (3a-o and 7a,b) is their
      appended aryl, heteroaryl and alkylthio substituent at position 6 and also
      alkylthio substituent at position 2. The rational design, synthesis, and
      evaluation of the in vitro antibacterial activity against six pathogenic bacteria
      including virulent and non-virulent strains of Mycobacterium tuberculosis is
      described. Some of the synthesized compounds (3c, 3h, 3i, 3o) have displayed only
      potent in vitro antimycobacterial activity with MIC of 0.75 microg/mL except 3i
      which also demonstrated activity against Escherichia coli at 12.5 microg/mL
      concentration. Only two compounds, 3a and 3b, demonstrated antibacterial activity
      against Pseudomonas aeruginosa and E. coli with MIC 12.5 microg/mL. All the
      synthesized compounds were also evaluated for their antimycotic activity against
      five pathogenic fungi but only some of them 3j-n and 7a,b were found most potent
      against Aspergillus fumigatus and Trichophyton mentagrophytes.

PMID- 11836093
TI  - Synthesis of mycothiol, 1D-1-O-(2-[N-acetyl-L-cysteinyl]amino-2-deoxy-alpha-D
      glucopyranosyl)-myo-inositol, principal low molecular mass thiol in the
      actinomycetes.
AB  - Members of the actinomycetes produce 1D-1-O-(2-[N-acetyl-L-cysteinyl]amino-2
      deoxy-alpha-D-glucopyranosyl)-myo-inositol or mycothiol 1 as principal low
      molecular mass thiol. Chemical synthesis of a biosynthetic precursor of
      mycothiol, the pseudodisaccharide 1D-1-O-(2-amino-2-deoxy-alpha-D-glucopyranosyl)
      myo-inositol 13 was achieved by the following steps: (1) Enantioselective
      synthesis gave the glycosyl acceptors (-)-2,3,4,5,6-penta-O-acetyl-D-myo-inositol
      D-7 and the corresponding L-isomer L-7. (2) Condensation of D-7 and L-7 with the
      glycosyl donor 3,4,6-tri-O-acetyl-2-deoxy-2-(2,4-dinitrophenylamino)-alpha-D
      glucopyranosylbromide afforded the corresponding alpha and beta anomeric
      products, which could be resolved by silica gel chromatography. (3) Deprotection
      of these by hydrolysis using an anion exchange resin gave 1D- and 1L-1-O-(2-amino
      2-deoxy-alpha-D-glucopyranosyl)-myo-inositol 13 and 15 and the corresponding beta
      coupled anomers 14 and 16. Only 13, and to a much lesser extent 15, were used by
      enzymes present in an ammonium sulphate fraction of a cellfree extract of
      Mycobacterium smegmatis for the enzymatic synthesis of mycothiol. In the absence
      of acetyl-SCoA, the immediate biosynthetic precursor of 1, desacetylmycothiol,
      was the major product.

PMID- 11836094
TI  - The enantiomers of carbocyclic 5'-norguanosine: activity towards Epstein-Barr
      virus.
AB  - (-)-5'-noraristeromycin (1) has shown antiviral activity towards, particularly
      cytomegalovirus, vaccinia virus and measles while its (+)-enantiomer (2) is
      effective towards hepatitis B virus. To determine if the antiviral
      characteristics of 1 and 2 extended to the guanine analogues (3 and 4), these
      enantiomers were prepared and evaluated against herpes simplex virus type 1 (HSV
      1) and type 2 (HSV-2), cytomegalovirus (CMV), varicella zoster virus (VZV),
      Epstein-Barr virus (EBV), human herpes virus type 6 (HHV-6), human herpes virus
      type 8 (HHV-8), vaccinia virus (VV), cowpox virus (CV), vesicular stomatitis
      virus (VSV), respiratory syncytial virus (RSV), hepatitis B virus (HBV), and
      human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2). The only activity
      found for 3 was for Epstein-Barr virus in VCA Elisa (EC50 0.78 microg/mL),
      immunofluorescence assay for VCA or gp 350/250 (1.8-4.0 microg/mL) and DNA
      hybridization (EC50 0.82 microg/mL) assays with no accompanying toxicity seen in
      the host Daudi cells. No activity was noted for 4.

PMID- 11836095
TI  - Synthesis, characterization and antitumor studies of Mn(II), Fe(III), Co(II),
      Ni(II), Cu(II) and Zn(II) complexes of N-salicyloyl-N'-o
      hydroxythiobenzhydrazide.
AB  - A new ligand N-salicyloyl-N'-o-hydroxythiobenzhydrazide (H2Sotbh) forms complexes
      [Mn(HSotbh)2], [Fe(Sotbh-H)(H2O)2], [M(Sotbh)] [M=Co(II), Cu(II) and Zn(II)] and
      [Ni(Sotbh)(H(2)O)2], which were characterized by various physico-chemical
      techniques. Mossbauer spectrum of [Fe(Sotbh-H)(H2O)2] reveals the quantum
      admixture of 5/2 and 3/2 spin-states. Mn(II), Cu(II) and Ni(II) complexes were
      observed to inhibit the growth of tumor in vitro, whereas, Fe(III), Co(II),
      Zn(II) complexes did not. In vivo administration of Mn(II), Cu(II) and Ni(II)
      resulted in prolongation of survival of tumor bearing mice. Tumor bearing mice
      administered with Mn(II), Cu(II) and Ni(II) complexes showed reversal of tumor
      growth associated induction of apoptosis in lymphocytes. The paper discusses the
      possible mechanisms and therapeutic implication of the H2Sotbh and its metal
      complexes in tumor regression and tumor growth associated immunosuppression.

PMID- 11836097
TI  - Study on the synthesis and PKA-I binding activities of 5-alkynyl tubercidin
      analogues.
AB  - 5-alkynyl tubercidin analogues were synthesized and their biological activities
      were evaluated. It was found that protein kinase A could be activated by 5
      alkynyl tubercidin (9a) and cAMP-binding ability to PKA-I was selectively
      inhibited by it. Molecular modeling showed that the interaction of 9a and PKA-I
      was associated with the existence of hydrophobic alkynyl group. During the
      synthesis of tubercidin analogues, a pair of 2'-carbonyl participating abnormal
      coupling products (11a, 11b) was obtained, the structure was identified by X-ray
      crystalline diffraction.

PMID- 11836096
TI  - Molecular modeling of protein tyrosine phosphatase 1B (PTP 1B) inhibitors.
AB  - Binding modes of a series of aryloxymethylphosphonates and monoanionic biosteres
      of phosphate group from a series of benzylic alpha,alpha-diflluoro phosphate and
      its biosteres as protein tyrosine phosphatase 1B (PTP 1B) inhibitors have been
      identified by molecular modeling techniques. We have performed docking and
      molecular dynamics simulations of these inhibitors with PTP 1B enzyme. The
      initial conformation of the inhibitors for docking was obtained from simulated
      annealing technique. Solvent accessible surface area calculations suggested that
      active site of PTP 1B is highly hydrophobic. The results indicate that for
      aryloxymethylphosphonates, in addition to hydrogen bonding interactions, Tyr46,
      Arg47, Asp48, Val49, Glu115, Lys116, Lys120 amino acid residues of PTP 1B are
      responsible for governing inhibitor potency of the compounds. The sulfonate and
      tetrazole functional groups have been identified as effective monoanionic
      biosteres of phosphate group and biphenyl ring system due to its favorable
      interactions with Glu115, Lys116, Lys120 residues of PTP 1B found to be more
      suitable aromatic functionality than naphthalene ring system for benzylic
      alpha,alpha-diflluoro phosphate and its biosteres. The information generated from
      the present study should be useful in the design of more potent PTP 1B inhibitors
      as anti diabetic agents.

PMID- 11836098
TI  - Syntheses and kinetic evaluation of racemic and optically active 2-benzyl-2
      methyl-3,4-epoxybutanoic acids as irreversible inactivators for carboxypeptidase
      A.
AB  - Racemic and optically active 2-benzyl-2-methyl-3,4-epoxybutanoic acids were
      synthesized and evaluated as inactivators for carboxypeptidase A, a
      representative zinc-containing proteolytic enzyme. Only the threo-form of the
      inactivator is effective and its potency in terms of k(inact)/K(I) value is lower
      by 42-fold compared with 2-benzyl-3,4-epoxybutanoic acid, indicating that the
      alpha-methyl group affects adversely in the inactivation contrary to the
      expectation that it would enhance the inactivation activity of the inhibitor
      through additional interactions of the methyl group with a small cavity (alpha
      methyl hole) present next to the S1' hydrophobic pocket. Of the enantiomeric
      pair, the inactivator having the (2S,3R)-configuration is more potent than its
      enantiomer by 44-fold. The observed kinetic results may be rationalized on the
      basis that the methyl group in the inactivator having the (2R,3S)-configuration
      experiences the van der Waals repulsive interactions with the bottom of the
      active site crevice in binding to CPA, casting a doubt on the presence of the so
      called alpha-methyl hole at the active site of carboxypeptidase A.

PMID- 11836100
TI  - Novel steroidal vinyl fluorides as inhibitors of steroid C17(20) lyase.
AB  - 20-fluoro-17(20)-pregnenolone derivatives were designed as enol mimics of
      pregnenolone. All of the targeted, novel fluoroolefins were potent inhibitors of
      C17(20) lyase.

PMID- 11836099
TI  - Studies on n-octyl-5-(alpha-D-arabinofuranosyl)-beta-D-galactofuranosides for
      mycobacterial glycosyltransferase activity.
AB  - The mycobacterial cell wall is a potential target for new drug development.
      Herein we report the preparation and activity of several n-octyl-5-(alpha-D
      arabinofuranosyl)-beta-D-galactofuranoside derivatives. A cell-free assay system
      has been utilized for determination of the ability of disaccharide analogues to
      act as arabinosyltransferase acceptors using [14C]-DPA as the glycosyl donor. In
      addition, in vitro inhibitory activity has been determined in a colorimetric
      broth microdilution assay system against MTB H37Ra and three clinical isolates of
      Mycobacterium avium complex (MAC). One of these disaccharides showed moderate
      activity against MTB. The biological evaluation of these disaccharides suggests
      that more hydrophobic analogues with a blocked reducing end showed better
      activity as compared to a totally deprotected disaccharide that more closely
      resembles the natural substrates in cell wall biosynthesis.

PMID- 11836101
TI  - Antioxidant potential of natural and synthesised polyprenylated hydroquinones.
AB  - The metabolites 2-octaprenyl-1,4-hydroquinone (1) and 2-(24-hydroxy)-octaprenyl
      1,4-hydroquinone (2), isolated from the sponge Ircinia spinosula, along with a
      series of synthetic derivatives, were evaluated for their antioxidant capacity,
      in order to establish a potential relationship between structural characteristics
      and antioxidant activity. The antioxidant potential of both natural and
      synthesised compounds was evaluated in vitro by their ability: (1) to interact
      with the stable free 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) and (2) to
      inhibit the peroxidation, induced by the Fe(++)/ascorbate system, of heat
      inactivated hepatic microsomal membrane lipids. Metabolite 1 presented a strong
      interaction with DPPH and had a moderate effect on lipid peroxidation, while
      metabolite 2 interacted extensively with DPPH and exhibited a significant effect
      against lipid peroxidation. All derivatives retaining the free 1,4-hydroquinone
      system maintained fully or partly the free radical scavenging capacity.

PMID- 11836102
TI  - Influence of 2-substituent on the activity of imidazo[1,2-a] pyridine derivatives
      against human cytomegalovirus.
AB  - The synthesis of various 2-substituted imidazo[1,2-a]pyridine bearing a thioether
      side chain in position 3 was reported. The new compounds were characterized by 1H
      and 13C NMR spectra. A conformational study was obtained by X-ray
      crystallographic analysis for 2-biphen-4-ylimidazopyridine 7. The antiviral
      activity against human cytomegalovirus (HCMV) was investigated. It was strongly
      influenced by the nature of C-2 substituent.

PMID- 11836103
TI  - Novel lipase-catalysed highly selective acetylation studies on D-arabino- and D
      threo-polyhydroxyalkyltriazoles.
AB  - Capabilities of lipases from Candida antarctica, Candida rugosa and porcine
      pancreas have been evaluated for regioselective acetylation of 2-phenyl-4-(D
      arabino-tetrahydroxybutyl)-2H-1,2,3-triazole, 2-phenyl-4-(D-arabino-O-1',2'
      isopropylidene-3',4'-dihydroxybutyl)-2H-1,2,3-triazole and 2-phenyl-4-(D-threo
      trihydroxypropyl)-2H-1,2,3-triazole, precursors for the synthesis of
      triazolylacyclonucleosides. C. antarctica lipase and porcine pancreatic lipase
      exhibited exclusive selectivity for the acetylation of primary hydroxyl group
      over secondary hydroxyl group(s) in all the three cases.

PMID- 11836104
TI  - Cyclic dibenzoylhydrazines reproducing the conformation of ecdysone agonists, RH
      5849.
AB  - We have investigated the biologically active conformation of the non-steroidal
      ecdysone agonist, 1-tert-butyl-1,2-dibenzoylhydrazine (RH-5849) by means of
      design, synthesis and conformational analysis of cyclic derivatives of RH-5849.
      Among the synthesized compounds, a 6-membered cyclic hydrazine bearing two
      benzoyl groups (5) exists in three conformational states in solution, and the
      major unsymmetrical conformer of 5 is similar to that of RH-5849 on the basis of
      1H NMR and X-ray analyses. The 3,3-dimethyl derivative of 5 (10) exists as a
      single unsymmetrical conformer. Although there is conformational similarity of
      the cyclic derivatives with RH-5849, these compounds did not show any hormonal or
      insecticidal activity. The hydrogen bonding character of the amide N-H group of
      the dibenzoylhydrazine seems to play a critical role in the appearance of the
      biological activity.

PMID- 11836105
TI  - Synthesis and antiviral activity evaluation of novel 2-phenyl-4-(D-arabino-4'
      cycloaminobutyl)triazoles: acyclonucleosides containing unnatural bases.
AB  - Five 2-phenyl-4-(D-arabino-4'-cycloamino-3'-hydroxy-O-1',2'-isopropylidene-butyl)
      2H-1,2,3-triazoles, acyclonucleosides containing unnatural bases have been
      synthesised by opening of the epoxide ring of 2-phenyl-4-(D-arabino-3',4'-epoxy-O
      1',2'-isopropylidenebutyl)-2H-1,2,3-triazole with the corresponding cyclic amines
      in 70-85% yields. The starting arabino-epoxytriazole was prepared in five steps
      starting from D-glucose in an overall yield of 15%. All the five
      triazolylacyclonucleosides were unambiguously identified on the basis of their
      spectral data. The structure of one of the intermediates, that is 2-phenyl-4-(D
      arabino-1',2',3',4'-tetrahydroxybutyl)-2H-1,2,3-triazole was confirmed by its X
      ray crystallographic studies. These acyclonucleosides were subjected to antiviral
      activity evaluation in CEM-SS cell-based anti HIV assay with the lymphocytropic
      virus strains HIV-1(IIIB) and HIV-1(RF).

PMID- 11836106
TI  - Dihydroxybergamottin caproate as a potent and stable CYP3A4 inhibitor.
AB  - We investigated the inhibitory activity of the furanocoumarin derivatives from
      grapefruit juice to the drug metabolizing enzyme, cytochrome P450 (CYP) 3A4.
      Although two known furanocoumarin dimers GF-I-1 (1) and GF-I-4 (2) showed potent
      CYP3A4 inhibition with IC50 value of 0.07 microM, a semi-synthetic
      dihydroxybergamottin caproate (11), which was more stable and more simple than
      the dimers, exhibited comparable activity against CYP3A4.

PMID- 11836107
TI  - Design and synthesis of a selective EP4-receptor agonist. Part 1: discovery of
      3,7-dithiaPGE1 derivatives and identification of their omega chains.
AB  - Improvement of EP4-receptor selectivity and the agonist activity by introduction
      of heteroatoms into the alpha chain of PGE1 was investigated. Among the compounds
      tested, 3,7-dithiaPGE1 4a exhibited good EP4-receptor selectivity and agonist
      activity. Further modification of the omega chain of 3,7-dithiaPGE1 was performed
      to improve EP4-receptor selectivity and agonist activity. Of the compounds
      produced, 16-phenyl-omega-tetranor-3,7-dithiaPGE1 4p possessing moderate EP4
      receptor selectivity and agonist activity, was identified as a new chemical lead
      for further optimization by modification of the aromatic moiety.

PMID- 11836108
TI  - Design and synthesis of a selective EP4-receptor agonist. Part 2: 3,7-dithiaPGE1
      derivatives with high selectivity.
AB  - To identify new highly selective EP4-agonists, further modification of the 16
      phenyl moiety of 1 was continued. 16-(3-methoxymethyl)phenyl derivatives 13-(6q)
      and 16-(3-ethoxymethyl)phenyl derivatives 13-(7e) showed more selectivity and
      potent agonist activity than 1. 16-(3-methyl-4-hydroxy)phenyl derivative 18-(14e)
      demonstrated excellent subtype selectivity, while both its receptor affinity and
      agonist activity were less potent than those of 13-(6q). Structure-activity
      relationships (SARs) are also discussed.

PMID- 11836109
TI  - Guanidinium and aminoimidazolinium derivatives of N-(4-piperidyl)propanamides as
      potential ligands for mu opioid and I2-imidazoline receptors: synthesis and
      pharmacological screening.
AB  - Derivatives of N-(1-phenethyl-4-piperidyl)propanamides incorporating guanidinium
      and 2-aminoimidazolinium groups have been prepared by a synthetic approach
      involving first introduction of a spacer between the piperidine and the
      functional group by reductive amination of piperidinone. The formation of each of
      these functional groups was carried out using N-N'-di(tert
      butoxycarbonyl)thiourea and 2-methylthioimidazolinium iodide, respectively. These
      structures have been designed to incorporate two pharmacologic goals into one
      entity. Radioligand binding assays have been used to study their affinity for
      opioid (mu, delta and kappa) and I2-imidazoline receptors. Two of them, 10 and
      16, showed high affinity for mu opioid receptors and functionally they had
      moderate analgesic properties in the hot plate and writhing tests. The in vitro
      studies on guinea pig ileum (GPI) indicated that both compounds are mu opioid
      agonists. In what concerns I2-imidazoline receptor activity, these derivatives
      showed low affinity around 6 to 7 times less than idazoxan.

PMID- 11836110
TI  - Molecular structure and stereoelectronic properties of herbicide sulphonylureas.
AB  - MO theoretical calculations were used with the aim to investigate the electronic
      properties of a number of sulphonylureas 1-8 which are employed as antifeedants.
      Quantum chemical descriptors [electron density, molecular electrostatic potential
      (MEP), the topology of frontier orbitals and reactivity index] were determined
      for these compounds, aimed both to obtain a deeper insight in their mechanism of
      action and to correlate these properties with their activity as inhibitors of ALS
      synthase.

PMID- 11836112
TI  - Application of non-parametric regression to quantitative structure-activity
      relationships.
AB  - Several non-parametric regressors have been applied to modelling quantitative
      structure-activity relationship (QSAR) data. Performances were benchmarked
      against multilinear regression and the nonlinear method of smoothing splines.
      Variable selection was explored through systematic combinations of different
      variables and combinations of principal components. For the training set examined
      -539 inhibitors of the tyrosine kinase, Syk--the best two-descriptor model had a
      5-fold cross-validated q2 of 0.43. This was generated by a multi-variate Nadaraya
      Watson kernel estimator. A subsequent, independent, test set of 371 similar
      chemical entities showed the model had some predictive power. Other approaches
      did not perform as well. A modest increase in predictive ability can be achieved
      with three descriptors, but the resulting model is less easy to visualise. We
      conclude that non-parametric regression offers a potentially powerful approach to
      identifying predictive, low-dimensional QSARs.

PMID- 11836111
TI  - Effect of modification of 6-[(aminoalkyl)amino]-7H-benzo[e]-perimidin-7-ones on
      their cytotoxic activity toward sensitive and multidrug resistant tumor cell
      lines. Synthesis and biological evaluation.
AB  - Benzoperimidines, a novel group of antitumor anthracenedione analogues, are of
      interest due to their ability to overcome multidrug resistance of tumor cells
      (Stefanska, B., Dzieduszycka, M., Bontemps-Gracz, M. M., Borowski, E., Martelli,
      S., Supino, R., Pratesi, G., De Cesare, MA., Zunino, F., Kusnierczyk, H.,
      Radzikowski, Cz. J. Med. Chem. 1999, 42, 3494). Although the structural factor
      essential for exhibiting this desirable property is the presence in the molecule
      of a fused heterocyclic ring, the cytotoxicity against resistant cells is highly
      influenced by the nature and location of the substituents. A series of novel
      synthetic derivatives, comprising monohydroxylated benzoperimidines and 2
      aminobenzoperimidines, allowed the establishment of an in vitro structure
      activity relationship for a panel of leukemia sensitive, as well as P-gp
      dependent multidrug resistance (MDR) and multidrug resistance associated protein
      dependent resistance (MRP) resistant cell lines. The membrane affinity for the
      compounds has also been determined.

PMID- 11836113
TI  - Synthesis of a novel class of non-peptide NK-2 receptor ligand, derived from 1
      phenyl-3-pyrrol-1-ylindan-2-carboxamides.
AB  - A series of trans,trans-1-phenyl-3-pyrrol-1-ylindan-2-carboxamide derivatives has
      been synthesized in eight steps starting from cinnamic acid or 3,3
      diphenylpropionic acid. The trans,trans configuration of these carboxamides has
      been established by X-ray analysis and by NOE experiments in NMR. These new
      compounds were evaluated for their potential NK-1, NK-2 and NK-3 receptors
      binding affinity. The N,N-disubstituted carboxamides bound selectively on NK-2
      receptors.

PMID- 11836114
TI  - 3,5-dibenzoyl-1,4-dihydropyridines: synthesis and MDR reversal in tumor cells.
AB  - Fifteen 4-phenyl-3,5-dibenzoyl-1,4-dihydropyridines (BzDHPs) (1-15) substituted
      at the 4-phenyl ring were synthesized and compared to their cytotoxic activity
      and multidrug resistance (MDR)-reversing activity in in vitro assay systems.
      Among them, 2-CF3 (5) (IC50=8.7 microM), 2-Cl (11) (IC50=7.0 microM) and 3-Cl
      (12) (IC50=7.0 microM) derivatives showed the highest cytotoxic activity against
      human oral squamous carcinoma (HSC-2) cells. The activity of P-glycoprotein (Pgp)
      response for MDR in tumor cells was reduced by some of derivatives (3, 4, 8, 12),
      verapamil (VP) and nifedipine (NP). These data suggest that 3,5-dibenzoyl-4-(3
      chlorophenyl)-1,4-dihydro-2,6-dimethylpyridine (12) can be recommended as a new
      drug candidate for MDR cancer treatment.

PMID- 11836115
TI  - Studies on the immuno-modulating and antitumor activities of Ganoderma lucidum
      (Reishi) polysaccharides: functional and proteomic analyses of a fucose
      containing glycoprotein fraction responsible for the activities.
AB  - A fucose-containing glycoprotein fraction which stimulates spleen cell
      proliferation and cytokine expression has been identified from the water-soluble
      extract of Ganoderma lucidum. Proteomic analysis of mouse spleen cells treated
      with this glycoprotein fraction showed approximately 50% change of the proteome.
      Further studies on the activities of this glycoprotein fraction through selective
      proteolysis and glycosidic cleavage indicate that a fucose containing
      polysaccharide fraction is responsible for stimulating the expression of
      cytokines, especially IL-1, IL-2 and INF-gamma.

PMID- 11836116
TI  - Formation of a fairly stable diazoate intermediate of 5-methyl-2'-deoxycytidine
      by HNO2 and NO, and its implication to a novel mutation mechanism in CpG site.
AB  - The intermediate produced from 5-methyl-2'-deoxycytidine ((5me)dCyd) by HNO2 and
      NO treatments was isolated and characterized. When 10mM (5me)dCyd was incubated
      with 100mM NaNO2 at pH 3.7 and 37 degrees C, a previously unidentified product
      was formed. The product was identified as a diazoate derivative of (5me)dCyd, 1
      (beta-D-2'-deoxyribofuranosyl)-5-methyl-2-oxopyrimidine-4-diazoate ((5me)dCyd
      diazoate), on the bases of several measurements including LC/MS. The time course
      of the concentration change of the diazoate showed a characteristic profile of a
      reaction intermediate, and the steady state concentration was 2.3 microM (0.023%
      yield). When an aqueous solution of 10mM (5me)dCyd (10 mL) was bubbled by NO at
      37 degrees C under aerobic conditions holding the pH around 7.4, the diazoate was
      also generated. The yield of the diazoate was 0.041 micromol (0.041% yield) at 20
      mmol of NO absorption. At physiological pH and temperature (pH 7.4, 37 degrees
      C), the diazoate was converted to dThd exclusively with a first order rate
      constant k=9.1x10(-6) x s(-1) (t(1/2)=21 h). These results show that the diazoate
      is generated as a relatively stable intermediate in the reactions of (5me)dCyd
      with HNO2 and NO and further suggest that the diazoate can be formed in cellular
      DNA with biologically relevant doses of HNO2 and NO.

PMID- 11836117
TI  - Synthesis of novel polyphenols consisted of ferulic and gallic acids, and their
      inhibitory effects on phorbol ester-induced Epstein-Barr virus activation and
      superoxide generation.
AB  - We prepared novel polyphenols which were esters composed of two naturally
      occurring products, ferulic and gallic acids, and investigated their inhibitory
      effects on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced Epstein-Barr virus
      (EBV) activation and superoxide (O2-) generation. Most of these compounds
      exhibited significant EBV activation suppression at a concentration of 20 microM
      and in particular, the ester 5f having 2-methyl-1-butyl group showed high
      activity. The suppressive effects on O2- generation were also observed in most of
      the esters.

PMID- 11836118
TI  - Synthesis and aldose reductase inhibitory activity of 5-arylidene-2,4
      thiazolidinediones.
AB  - Several (Z)-5-arylidene-2,4-thiazolidinediones were synthesized and tested as
      aldose reductase inhibitors (ARIs). The most active of the N-unsubstituted
      derivatives (2) exerted the same inhibitory activity of Sorbinil. The
      introduction of an acetic side chain on N-3 of the thiazolidinedione moiety led
      to a marked increase in lending inhibitory activity, conducting to the discovery
      of a very potent ARI (4c), whose activity level (IC50=0.13 microM) was in the
      same range of Tolrestat. Moreover, the corresponding methyl esters (3), devoid of
      any acidic functionality, showed appreciable inhibitory activity similar to that
      of the N-unsubstituted compounds. It was also found that the substitution pattern
      on the 5-benzylidene moiety markedly influenced the activity of N-unsubstituted
      2,4-thiazolidinediones 2, compounds with substituents at the meta position being
      generally more effective than the para-substituted ones; however, this SAR was
      not evidenced in acetates 3 and acids 4.

PMID- 11836119
TI  - Synthesis and capillary electrophoretic analysis of enantiomerically enriched
      reference standards of MDMA and its main metabolites.
AB  - Enantiomerically-enriched (S)-3,4-methylenedioxymethamphetamine (MDMA) and its
      main metabolites (S)-4-hydroxy-3-methoxymethamphetamine (HMMA) and (S)-3,4
      dihydroxymethamphetamine (HHMA) were prepared for unequivocal identification of
      the differential enantioselective metabolism of these compounds as well as for
      its application in the analysis of biological samples. Capillary electrophoresis
      with cyclodextrin derivatives and a chemical correlation of (S)-MDMA, (S)-HMMA
      and (S)-HHMA has been performed to assign the absolute stereochemistry of major
      isomers in analytical standards enriched with such enantiomers.

PMID- 11836120
TI  - Development of a highly selective EP2-receptor agonist. Part 1: identification of
      16-hydroxy-17,17-trimethylene PGE2 derivatives.
AB  - Design and synthesis of an EP2-receptor selective agonist began with the chemical
      modification of alpha- and omega-chains of butaprost 1a, which exhibits an
      affinity for the IP-receptor. Two series of prostaglandin (PG) analogues with a
      16-hydroxy-17,17-trimethylene moiety as an omega-chain were identified. Among
      those tested, 4a,b,e,f,h and 6a,b,e,f,h were found to be highly selective EP2
      receptor agonists. Structure-activity relationships are discussed.

PMID- 11836121
TI  - Development of a highly selective EP2-receptor agonist. Part 2: identification of
      16-hydroxy-17,17-trimethylene 9beta-chloro PGF derivatives.
AB  - Further chemical modification of 1a and 2 was undertaken to identify a more
      chemically stable selective EP2-receptor agonist for development as a clinical
      candidate. 9beta-chloro PG analogues 4a-e and 5a, c-e were found to be potent and
      selective EP2-receptor agonists. Among them, the compound 4aLy, which is a
      chemically stabilized lysine salt of 4a, exhibited an excellent profile both in
      biological activities and physicochemical properties. The agonist 4aLy was found
      to suppress uterine motility in anesthetized pregnant rats, while PGE2 stimulated
      uterine motility. Structure-activity relationships (SARs) are discussed.

PMID- 11836122
TI  - New 2,N6-disubstituted adenosines: potent and selective A1 adenosine receptor
      agonists.
AB  - A number of adenosine analogues substituted in the 2- and N6-positions were
      synthesized and evaluated for affinity, functional potency and intrinsic activity
      at the A1 and A2A adenosine receptors (AR). Three classes of N6-substituents were
      tested; norbornen-2-yl (series 1), norborn-2-yl (series 2) and 5,6-epoxynorborn-2
      yl (series 3). The halogens; fluoro, bromo, and iodo were evaluated as C-2
      substituents. All compounds showed relatively high affinity (nanomolar) for the
      A1AR and high potency for inhibiting (-)isoproterenol-stimulated cAMP
      accumulation in hamster smooth muscle DDT1 MF-2 cells with the 2-fluoro
      derivatives from each series having the highest affinity. All of the derivatives
      showed the same intrinsic activity as CPA. At the A2AAR, all of the derivatives
      showed relatively low affinity and potency (micromolar) for stimulating cAMP
      accumulation in rat pheochromocytoma PC-12 cells. The intrinsic activity of the
      derivatives compared to CGS 21680 was dependent upon the halogen substituent in
      the C-2 position with most showing partial agonist activity. Of particular
      interest is 2-iodo-N6-(2S-endo-norborn-2-yl)adenosine (5e), which is over 100
      fold selective for the A1AR, is a full agonist at this receptor subtype and has
      no detectable agonist activity at the A2AAR.

PMID- 11836123
TI  - Psammaplin A, a chitinase inhibitor isolated from the Fijian marine sponge
      Aplysinella rhax.
AB  - Several brominated tyrosine derived compounds, psammaplins A (1), K (2) and L (3)
      as well as bisaprasin (4) were isolated from the Fijian marine sponge Aplysinella
      rhax during a bioassay guided isolation protocol. Their structures were
      determined using NMR and MS techniques. Psammaplin A was found to moderately
      inhibit chitinase B from Serratia marcescens, the mode of inhibition being non
      competitive. Crystallographic studies suggest that a disordered psammaplin A
      molecule is bound near the active site. Interestingly, psammaplin A was found to
      be a potent antifungal agent.

PMID- 11836124
TI  - SAR directed design and synthesis of novel beta(1-4)-glucosyltransferase
      inhibitors and their in vitro inhibition studies.
AB  - This paper describes SAR directed design and synthesis of novel beta(1-4)
      glucosyltransferase (BGT) inhibitors. The designed inhibitors 1-5 provide
      conformational mimicry of the transition-state in glucosyltransfer reactions. The
      compounds were tested for in vitro inhibitory activity against (BGT) and the
      inhibition kinetics were examined. Three of the designed molecules were found to
      be potential inhibitors of BGT having IC50 values in micromolar (microM) range.
      Useful structure-activity relationships were established, which provide
      guidelines for the design of future generations of inhibitors of BGT.

PMID- 11836125
TI  - A facile one-pot synthesis of 4,5-diaryl-2,2-dimethyl-3(2H)-furanones.
AB  - An efficient and practical one-pot synthesis of 4,5-diaryl-2,2-dimethyl-3(2H)
      furanones has been achieved from 1,2-diarylethanones and 2-bromoisobutyryl
      cyanide in the presence of excess base, by employing the 'hard soft acid base'
      principle. The reaction scope of 2-bromoisobutyryl cyanide could be expanded to
      prepare a variety of 2,2-dimethyl-3(2H)-furanone derivatives other than 4,5
      diaryl-2,2-dimethyl-3(2H)-furanones.

PMID- 11836126
TI  - Synthesis and in vitro muscarinic activities of a series of 1,3-diazacycloalkyl
      carboxaldehyde oxime derivatives.
AB  - A series of 1,3-diazacycloalkyl carboxaldehyde oxime derivatives was synthesized
      and tested for muscarinic activity in receptor binding assays using [3H]
      oxotremorine-M (OXO-M) and [3H]-pirenzepine (PZ) as ligands. Potential muscarinic
      agonistic or antagonistic properties of the compounds were determined using
      binding studies measuring their potencies to inhibit the binding of OXO-M and PZ.
      Preferential inhibition of OXO-M binding was used as an indicator for potential
      muscarinic agonistic properties; this potential was confirmed in functional
      studies on isolated organs.

PMID- 11836127
TI  - Insights into the selective inhibition of Candida albicans secreted aspartyl
      protease: a docking analysis study.
AB  - Severe fungal infections have taken precedence over other bacterial infections.
      Of the several fungal species, Candida albicans and others belonging to the genus
      Candida are responsible for several clinically important fungal infections.
      Emerging cases of drug resistance to the currently available drugs has limited
      the spectrum of currently available antifungal agents. Thus, it is imperative
      that new biochemical targets are identified so that better effective and
      selective agents can be developed. Many enzymes contribute towards the complex
      disease process of fungal infections; the secreted aspartyl protease (SAP),
      expressed both in vitro and during infection, has been implicated as one of the
      major virulence factors of C. albicans. Three-dimensional crystal structures of
      C. albicans SAP and closely related clinical isolate designated as SAP2X
      complexed with the same potent inhibitor A-70450 have been reported. Several
      analogues of A-70450 with potent C. albicans SAP2X inhibitory activity are also
      known. However, the structural effects of the binding of these compounds with the
      enzyme active site are not completely understood. Our efforts in this direction
      involve the docking analysis of C. albicans SAP2X inhibitors complexed with SAP2X
      enzyme, which is reported in this work. Docking analysis was performed on a set
      of molecules with differing selectivities and inhibitory potencies towards C.
      albicans, renin and cathepsin D. The structural effects of ligand binding were
      analyzed on the basis of hydrophobic and hydrogen bond interactions, binding
      energy analysis, interaction energies, rms deviations, etc. in the resulting
      energy-minimized structures of the receptor-ligand complexes. Structural analysis
      of the resulting models indicates that hydrophobic and hydrogen bonding
      interactions together with binding and interaction energies are responsible for
      selective inhibition of C. albicans SAP2X. Hydrophobic and hydrogen bonding
      interactions in the various subsites of the enzyme, contributing to both increase
      as well as decrease in selectivity of the molecules have been detailed. Hydrogen
      bonding interaction plays an important role for amino acid residues such as Gly
      85, Asp-86, Asp-32, Asp-218, Tyr-225, Ala-133, and so on. Significant hydrophobic
      interactions with the S3, S2 and S2' subsites contribute to selectivity of the
      compounds. These molecular modeling analyses should, in our view, contribute for
      further development of selective C. albicans secreted aspartyl protease
      inhibitors.

PMID- 11836128
TI  - Phenolic modification as an approach to improve the pharmacology of the 3-acyloxy
      2-benzylpropyl homovanillic amides and thioureas, a promising class of vanilloid
      receptor agonists and analgesics.
AB  - In order to improve the analgesic activity and pharmacokinetics of thioureas 2
      and 3, which we previously developed as potent vanilloid receptor (VR) agonists,
      we prepared and characterized phenolic modifications of them and of their amide
      surrogates (7, 8). The aminoethyl analogue of the amide template 13 was a potent
      analgesic with an EC50=0.96 microg/kg in the AA-induced writhing test and with
      better in vivo stability than the parent phenol.

PMID- 11836129
TI  - QSAR study on toxicity to aqueous organisms using the PI index.
AB  - We have attempted to develop quantitative structure-toxicity relationships
      (QSTRs) to predict hydrophobicity (logP) as well as toxicity (pEC50 microm) of
      benzene derivatives using recently introduced Padmakar-Ivan (PI) index. The
      results have shown that both logP as well as pEC50 of benzene derivatives can be
      modelled excellently in multiparametric models in that the PI index and some
      indicator parameters are involved. The predictive ability of the models is
      discussed on the basis of the cross-validation method. The superiority of the PI
      index over several other topological indices is critically examined.

PMID- 11836130
TI  - Syntheses of ferulic acid derivatives and their suppressive effects on
      cyclooxygenase-2 promoter activity.
AB  - Novel ferulic acid derivatives in which feruloyl groups were attached to the
      hydroxyl groups of myo-inositol 1,3,5-orthoformate derivatives were synthesized.
      These feruloyl-myo-inositols suppressed the cyclooxygenase-2 (COX-2) promoter
      activity in a concentration-dependent manner. Among the examined compounds,
      compound 9 showed the highest activity. A treatment with 100 microM of compound 9
      for 24 h resulted in a 50% decrease of COX-2 promoter activity without marked
      cytotoxicity. Both the molecular structure in which two ferulic acid moieties are
      facing each other and the molecular hydrophobicity may be essential for the
      suppression of COX-2 promoter activity.

PMID- 11836132
TI  - Methods for modeling and predicting mechanical deformations of the breast under
      external perturbations.
AB  - Currently, high field (1.5 T) superconducting MR imaging does not allow live
      guidance during needle breast procedures. The current procedure allows the
      physician only to calculate approximately the location and extent of a cancerous
      tumor in the compressed patient breast before inserting the needle. It can then
      become relatively uncertain that the tissue specimen removed during the biopsy
      actually belongs to the lesion of interest. A new method for guiding clinical
      breast biopsy is presented, based on a deformable finite element model of the
      breast. The geometry of the model is constructed from MR data, and its mechanical
      properties are modeled using a non-linear material model. This method allows
      imaging the breast without or with mild compression before the procedure, then
      compressing the breast and using the finite element model to predict the tumor's
      position during the procedure. A silicon phantom containing a stiff inclusion was
      imaged uncompressed then compressed. A model of the phantom was constructed and
      compressed using custom-written software, and also using a commercial FEM
      simulation package. The displacement of the inclusion's corners was recorded both
      in the real phantom and in the two compressed models. A patient's breast was
      imaged uncompressed then compressed. A deformable model of the uncompressed
      breast was constructed, then compressed. The displacement of a cyst and of two
      vitamin E pills taped to the surface of the breast were recorded both in the real
      and in the modeled breast. The entire procedure lasted less than a half-hour,
      making it clinically useful. The results show that it is possible to create a
      deformable model of the breast based on finite elements with non-linear material
      properties, capable of modeling and predicting breast deformations in a
      clinically useful amount of time.

PMID- 11836133
TI  - Four-dimensional processing of deformable cardiac PET data.
AB  - A four-dimensional deformable motion algorithm is described for use in the motion
      compensation of gated cardiac positron emission tomography. The algorithm makes
      use of temporal continuity and a non-uniform elastic material model to provide
      improved estimates of heart motion between time frames. Temporal continuity is
      utilized in two ways. First, incremental motion fields between adjacent time
      frames are calculated to improve estimation of long-range motion between distant
      time frames. Second, a consistency criterion is used to insure that the image
      match between distant time frames is consistent with the deformations used to
      match adjacent time frames. The consistency requirement augments the algorithm's
      ability to estimate motion between noisy time frames, and the concatenated
      incremental motion fields improve estimation for large deformations. The
      estimated motion fields are used to establish a voxel correspondence between
      volumes and to produce a motion-compensated composite volume.

PMID- 11836134
TI  - Evaluation of image features and search strategies for segmentation of bone
      structures in radiographs using Active Shape Models.
AB  - In this paper, we evaluate various image features and different search strategies
      for fitting Active Shape Models (ASM) to bone object boundaries in digitized
      radiographs. The original ASM method iteratively refines the pose and shape
      parameters of the point distribution model driving the ASM by a least squares fit
      of the shape to update the target points at the estimated object boundary
      position, as determined by a suitable object boundary criterion. We propose an
      improved search procedure that is more robust against outlier configurations in
      the boundary target points by requiring subsequent shape changes to be smooth,
      which is imposed by a smoothness constraint on the displacement of neighbouring
      target points at each iteration and implemented by a minimal cost path approach.
      We compare the original ASM search method and our improved search algorithm with
      a third method that does not rely on iteratively refined target point positions,
      but instead optimizes a global Bayesian objective function derived from
      statistical a priori contour shape and image models. Extensive validation of
      these methods on a database containing more than 400 images of the femur, humerus
      and calcaneus using the manual expert segmentation as ground truth shows that our
      minimal cost path method is the most robust. We also evaluate various measures
      for capturing local image appearance around each boundary point and conclude that
      the Mahalanobis distance applied to normalized image intensity profiles extracted
      normal to the shape is the most suitable criterion among the tested ones for
      guiding the ASM optimization.

PMID- 11836135
TI  - Estimating the effective degrees of freedom in univariate multiple regression
      analysis.
AB  - The general linear model provides the most widely applied statistical framework
      for analyzing functional MRI (fMRI) data. With the increasing temporal resolution
      of recent scanning protocols, and more elaborate data preprocessing schemes, data
      independency is no longer a valid assumption. In this paper, we revise the
      statistical background of the general linear model in the presence of temporal
      autocorrelations. First, when detecting the activation signal, we explicitly
      account for the temporal autocorrelation structure, which yields a generalized F
      test and the associated corrected (or effective) degrees of freedom (DOF). The
      proposed approach is data driven and thus independent of any specific
      preprocessing method. Then, for event-related protocols, we propose a new model
      for the temporal autocorrelations ("damped oscillator" model) and compare this
      model to another, previously used in the field (first-order autoregressive model,
      or AR(1) model). In the case of long fMRI time series, an efficient approximation
      for the number of effective DOF is provided for both models. Finally, the
      validity of our approach is assessed using simulated and real fMRI data and is
      compared with more conventional methods.

PMID- 11836136
TI  - Chronic arsenic poisoning from burning high-arsenic-containing coal in Guizhou,
      China.
AB  - Arsenic is an environmental hazard and the reduction of drinking water arsenic
      levels is under consideration. People are exposed to arsenic not only through
      drinking water but also through arsenic-contaminated air and food. Here we report
      the health effects of arsenic exposure from burning high arsenic-containing coal
      in Guizhou, China. Coal in this region has undergone mineralization and thus
      produces high concentrations of arsenic. Coal is burned inside the home in open
      pits for daily cooking and crop drying, producing a high concentration of arsenic
      in indoor air. Arsenic in the air coats and permeates food being dried producing
      high concentrations in food; however, arsenic concentrations in the drinking
      water are in the normal range. The estimated sources of total arsenic exposure in
      this area are from arsenic-contaminated food (50-80%), air (10-20%), water (1
      5%), and direct contact in coal-mining workers (1%). At least 3,000 patients with
      arsenic poisoning were found in the Southwest Prefecture of Guizhou, and
      approximately 200,000 people are at risk for such overexposures. Skin lesions are
      common, including keratosis of the hands and feet, pigmentation on the trunk,
      skin ulceration, and skin cancers. Toxicities to internal organs, including lung
      dysfunction, neuropathy, and nephrotoxicity, are clinically evident. The
      prevalence of hepatomegaly was 20%, and cirrhosis, ascites, and liver cancer are
      the most serious outcomes of arsenic poisoning. The Chinese government and
      international organizations are attempting to improve the house conditions and
      the coal source, and thereby protect human health in this area.

PMID- 11836137
TI  - Cancer risk assessment for arsenic exposure through oyster consumption.
AB  - Risk is assessed on the basis of assumptions, but this practice might not be well
      received by the general public. To avoid miscommunication, the assumptions should
      be stated clearly in reporting the results. Recently, a report on an assessment
      of the cancer risk associated with consumption of oysters caused a panic among
      consumers in Taiwan and produced significant effects on related industries. A
      group of researchers measured the arsenic content in oysters in the Taiwan area
      and conducted a cancer risk assessment accordingly. The results, published in a
      research article in an international journal, included a lifetime cancer risk
      estimate of 5.10/10(-4) as calculated based on the assumption that a person
      consumes oysters with the highest arsenic level (19.3 mg/g dry weight) at the
      highest rate (139 g/day) for 30 years. A national newspaper in Taiwan translated
      part of the article and published results that focused on the finding that this
      estimate was more than 500 times higher than what would be considered acceptable
      by the U.S. Environmental Protection Agency. As a result, most consumers stopped
      purchasing oysters, and the related industries suffered substantial losses. The
      newspaper's omission of the key assumptions in the risk assessment and the
      extreme assumptions made in the risk assessment led to this tragedy. This event
      demonstrated the importance of careful communication of risk assessment results.

PMID- 11836139
TI  - Public health consequences of mercury spills: Hazardous Substances Emergency
      Events Surveillance system, 1993-1998.
AB  - We analyzed data from states that participated in the Hazardous Substances
      Emergency Events Surveillance (HSEES) system maintained by the Agency for Toxic
      Substances and Disease Registry to describe the public health consequences of
      mercury releases. From 1993 through 1998, HSEES captured 406 events in which
      mercury was the only substance released. Schools and universities, private
      residences, and health care facilities were the most frequent locations involved
      in mercury events, and human error was the contributing factor for most of the
      releases. Fourteen persons experienced adverse health effects as a result of the
      releases. An additional 31 persons had documented elevated levels of mercury in
      the blood. No fatalities resulted. Evacuations were ordered in 90 (22%) of the
      events, and the length of evacuation ranged from 1 hr to 46 days. Mercury spills
      have a significant public health impact and economic burden. Some actions that
      could potentially lessen the consequences of mercury spills are to switch to
      mercury-free alternatives, train people in the safe handling and disposal of
      mercury, and keep mercury securely stored when it is necessary to have it on
      hand.

PMID- 11836138
TI  - Dichlorodiphenyltrichloroethane (DDT): ubiquity, persistence, and risks.
AB  - Due to uncontrolled use for several decades, dichlorodiphenyltrichloroethane
      (DDT), probably the best known and most useful insecticide in the world, has
      damaged wildlife and might have negative effects on human health. This review
      gives a brief history of the use of DDT in various countries and presents the
      results of epidemiologic and experimental studies of carcinogenesis. Even though
      its use has been prohibited in most countries for ecologic considerations, mainly
      because of its negative impact on wildlife, it is still used in some developing
      countries for essential public health purposes, and it is still produced for
      export in at least three countries. Due to its stability and its capacity to
      accumulate in adipose tissue, it is found in human tissues, and there is now not
      a single living organism on the planet that does not contain DDT. The possible
      contribution of DDT to increasing the risks for cancers at various sites and its
      possible role as an endocrine disruptor deserve further investigation. Although
      there is convincing experimental evidence for the carcinogenicity of DDT and of
      its main metabolites DDE and DDD, epidemiologic studies have provided contrasting
      or inconclusive, although prevailingly negative, results. The presence and
      persistence of DDT and its metabolites worldwide are still problems of great
      relevance to public health. Efficient pesticides that do not have the negative
      properties of DDT, together with the development of alternative methods to fight
      malaria, should be sought with the goal of completely banning DDT.

PMID- 11836140
TI  - Protein kinase C activity and the relations between blood lead and
      neurobehavioral function in lead workers.
AB  - At picomolar concentrations, lead activates protein kinase C (PKC). This
      activation has been implicated in the neurotoxicity of lead. No prior study has
      evaluated the association of PKC activity with neurobehavioral function in
      humans. The purpose of this study was to determine whether PKC activity is
      associated with neurobehavioral function or modifies the relationship between
      blood lead levels and neurobehavioral test scores. In this cross-sectional study
      of 212 current lead workers in the Republic of Korea, we assessed blood lead
      levels, neurobehavioral test scores, and PKC activity. PKC activity was
      determined by measuring the levels of phosphorylation of three erythrocyte
      membrane proteins (spectrin and the 52-kDa and 48-kDa subunits of band 4.9),
      using an in vitro back-phosphorylation assay. When linear regression was used to
      control for confounding variables, blood lead was a significant predictor of
      decrements in performance on tests of psychomotor function, manual dexterity, and
      executive ability. In linear regression models, back-phosphorylation levels were
      not associated with neurobehavioral test scores, but when dichotomized at the
      median, back-phosphorylation levels modified the relationship between blood lead
      and test scores. For spectrin and the 52-kDa and 48-kDa subunits of band 4.9, 5,
      2, and 5 of 14 interaction terms, respectively, had associated p-values less than
      0.10, all with positive signs, indicating that blood lead was associated with
      worse test scores only in subjects with lower back-phosphorylation levels. These
      data indicate that blood lead levels are associated with decrements in
      neurobehavioral test scores, mainly in the domains of manual dexterity and
      psychomotor function, but only in subjects with lower in vitro back
      phosphorylation levels, which is equivalent to higher in vivo PKC activity. We
      hypothesize that subjects with higher PKC activity in the presence of lead may be
      more susceptible to the health effects of lead.

PMID- 11836141
TI  - Effects of pentachlorophenol and tetrachlorohydroquinone on mitogen-activated
      protein kinase pathways in Jurkat T cells.
AB  - When Jurkat human T cells were incubated with 20 microM of pentachlorophenol
      (PCP) or its metabolite, tetrachlorohydroquinone (TCHQ), for 10 hr, flow
      cytometric analyses revealed marked increase in the number of apoptotic cells.
      DNA fragmentation was also observed in these cells. TCHQ was more potent than PCP
      in causing apoptosis. After incubation with 20 microM TCHQ for 1 hr, all mitogen
      activated protein kinases (MAPKs) examined [i.e., extracellular signal-regulated
      protein kinase (ERK), p38, and c-Jun NH(2)-terminal kinase (JNK)] were
      phosphorylated, whereas no clear phosphorylation was induced by PCP. TCHQ-induced
      apoptosis was markedly suppressed by treatment with a p38 inhibitor (SB203580)
      and mildly (but significantly) suppressed by treatment with a MAPK/ERK kinase
      inhibitor (U0126). When cells were treated with both inhibitors at the same time,
      TCHQ-induced apoptosis disappeared almost completely. PCP-induced apoptosis was
      also suppressed by SB203580 and/or U0126. Nevertheless, treatment with LL-Z1640
      2, which inhibits JNK phosphorylation, did not suppress the apoptosis caused by
      either TCHQ or PCP. Thus, p38 and ERK appear to be important signal transduction
      pathways leading to apoptosis in a human T-cell line exposed to a ubiquitous
      pollutant or its metabolite in the general and occupational environment.

PMID- 11836142
TI  - Nitrous acid, nitrogen dioxide, and ozone concentrations in residential
      environments.
AB  - Nitrous acid (HONO) may be generated by heterogeneous reactions of nitrogen
      dioxide and direct emission from combustion sources. Interactions among nitrogen
      oxides and ozone are important for outdoor photochemical reactions. However,
      little is known of indoor HONO levels or the relationship between residential
      HONO, NO(2), and O(3) concentrations in occupied houses. Six-day integrated
      indoor and outdoor concentrations of the three pollutants were simultaneously
      measured in two communities in Southern California using passive samplers. The
      average indoor HONO concentration was 4.6 ppb, compared to 0.9 ppb for outdoor
      HONO. Average indoor and outdoor NO(2)concentrations were 28 and 20.1 ppb,
      respectively. Indoor O(3) concentrations were low (average 14.9 ppb) in
      comparison to the outdoor levels (average 56.5 ppb). Housing characteristics,
      including community and presence of a gas range, were significantly associated
      with indoor NO(2) and HONO concentrations. Indoor HONO levels were closely
      correlated with indoor NO(2) levels and were about 17% of indoor NO(2)
      concentrations. Indoor HONO levels were inversely correlated with indoor O(3)
      levels. The measurements demonstrated the occurrence of substantial residential
      indoor HONO concentrations and associations among the three indoor air
      pollutants.

PMID- 11836143
TI  - Effects of exposure to low levels of environmental cadmium on renal biomarkers.
AB  - We conducted a study among residents of a small community contaminated with heavy
      metals from a defunct zinc smelter and residents from a comparison community to
      determine whether biologic measures of cadmium exposure were associated with
      biomarkers of early kidney damage. Creatinine-adjusted urinary cadmium levels did
      not differ between the smelter and comparison communities; thus we combined
      individuals from both communities (n = 361) for further analyses. The overall
      mean urinary cadmium level was low, 0.26 microg/g creatinine, similar to
      reference values observed in the U.S. general population. For children ages 6-17
      years, urinary concentration of N-acetyl-beta-D-glucosaminidase (NAG), alanine
      aminopeptidase (AAP), and albumin were positively associated with urinary
      cadmium, but these associations did not remain statistically significant after
      adjusting for urinary creatinine and other potential confounders. For adults ages
      18 or older, urinary concentration of NAG, AAP, and albumin were positively
      associated with urinary cadmium. The associations with NAG and AAP but not with
      albumin remained statistically significant after adjusting for creatinine and
      other potential confounders. We found a positive dose-effect relationship between
      levels of creatinine-adjusted urinary cadmium and NAG and AAP activity, and
      statistically significant differences in mean activity for these two enzymes
      between the highest (> or =1.0 microg cadmium/g creatinine) and the lowest (< or
      =0.25 microg cadmium/g creatinine) exposure groups. The findings of this study
      indicate that biologic measures of cadmium exposure at levels below 2.0 microg/g
      creatinine may produce measurable changes in kidney biomarkers.

PMID- 11836144
TI  - 3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) and mutagenic activity
      in Massachusetts drinking water.
AB  - There is limited information on the prevalence of the potent mutagen 3-chloro-4
      (dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) in U.S. water supplies. We
      measured MX concentrations and mutagenic activity in tap water samples from 36
      surface water systems throughout Massachusetts. We found MX levels much higher
      (up to 80 ng/L) than previously reported in the United States. We also evaluated
      the role of water treatment on mutagenic activity and disinfection by-product
      formation. After adjusting for other covariates, chloramination and filtration
      were the most important treatment options for reducing mutagenic activity and
      disinfection by-product formation. Multiple chlorine application (before and
      after filtration) was associated with increased mutagenicity. Chlorine dose, pH,
      and total organic carbon were also associated with mutagenicity, MX, and total
      trihalomethane (TTHM) concentration. Seasonal variation was evident for MX and
      mutagenic activity, with higher levels occurring in the spring compared to the
      fall. In contrast, TTHM concentrations were greater in the fall.

PMID- 11836145
TI  - Association of the blood/air partition coefficient of 1,3-butadiene with blood
      lipids and albumin.
AB  - Pulmonary gas uptake is a function of the blood solubility of a vapor, indicated
      by the blood/air partition coefficient. We hypothesized that blood lipid
      compositions are associated with the blood/air partition coefficients of
      lipophilic toxic vapors such as 1,3-butadiene. Our goal was to investigate cross
      sectional and longitudinal relationships of blood triglycerides, total
      cholesterol, and albumin to the blood/air partition coefficient of butadiene. We
      collected blood samples from 24 subjects at three time points: a fasting baseline
      and 2 and 4 hr after drinking a standardized high-fat milk shake (107 g fat, 80 g
      sugar, and 27 g protein). The blood/air partition coefficient was determined
      using the closed vial-equilibrium technique. Triglycerides and total cholesterol
      were analyzed by an enzymatic method, and albumin was analyzed with an
      immunoassay technique. We used multiple linear regression and general linear
      models to examine the cross-sectional and longitudinal relationship,
      respectively. The results showed that the blood/air partition coefficient of
      butadiene was cross-sectionally associated only with triglycerides at baseline,
      and longitudinally related to baseline triglycerides, total cholesterol, and the
      change in triglycerides over time. The blood/air partition coefficient of
      butadiene increased, on average, by approximately 20% and up to 40% for subjects
      with borderline higher triglyceride levels after ingestion of a standardized milk
      shake. In addition, a time factor beyond lipids was also significant in
      predicting the blood/air partition coefficient of butadiene. This may represent
      the effects of other unmeasured parameters related to time or time of day on the
      blood/air partition coefficient of butadiene. Because the blood/air partition
      coefficient is a major determinant of gas uptake, ingestion of a high fat meal
      before this type of exposure may significantly increase an individual's absorbed
      dose, possibly increasing the risk of adverse effects.

PMID- 11836146
TI  - A novel endocrine-disrupting agent in corn with mitogenic activity in human
      breast and prostatic cancer cells.
AB  - Housing adult rats on ground corncob bedding impedes male and female mating
      behavior and causes acyclicity in females. The suppressive effects on ovarian
      cyclicity are mimicked by a mitogenic agent purified from the ground corncob
      bedding material (corn mitogen; CM), which stimulates the proliferation of
      estrogen receptor (ER)-positive (MCF-7 cells) and ER-negative (MDA-MD-231 cells)
      breast cancer cells. Purified CM does not compete for [(3)H]estradiol binding to
      ER or nuclear type II sites, and its effects on MCF-7 breast cancer cell
      proliferation are not blocked by the antiestrogen ICI-182,780. These results
      suggest that the active component is unlikely to be a phytoestrogen,
      bioflavonoid, mycotoxin, or other known endocrine-disrupting agent that modifies
      cell growth via ER or type II [(3)H]estradiol binding sites. CM also stimulates
      the proliferation of PC-3 human prostatic cancer cells in vitro, and the growth
      rate of PC-3 cell xenografts is accelerated in nude male mice housed on ground
      corncob as opposed to pure cellulose bedding. Consequently, this endocrine
      disrupting agent in ground corncob bedding may influence behavioral and
      physiologic reproductive response profiles and malignant cell proliferation in
      experimental animals. Fresh corn (kernels and cob) or corn tortillas also contain
      CM, indicating that human exposure is likely; consequently, CM and/or related
      mitogens in corn products may influence human health and development.

PMID- 11836147
TI  - A competitive ELISA to detect brevetoxins from Karenia brevis (formerly
      Gymnodinium breve) in seawater, shellfish, and mammalian body fluid.
AB  - We developed a competitive enzyme-linked immunosorbent assay (ELISA) to analyze
      brevetoxins, using goat anti-brevetoxin antibodies obtained after immunization
      with keyhole limpet hemocyanin-brevetoxin conjugates, in combination with a three
      step signal amplification process. The procedure, which used secondary
      biotinylated antibodies, streptavidine-horseradish peroxidase conjugate, and
      chromogenic enzyme substrate, was useful in reducing nonspecific background
      signals commonly observed with complex matrices. This competitive ELISA detected
      brevetoxins in seawater, shellfish extract and homogenate, and mammalian body
      fluid such as urine and serum without pretreatment, dilution, or purification. We
      investigated the application of this technique for shellfish monitoring by
      spiking shellfish meat with brevetoxins and by analyzing oysters from two
      commercial shellfish beds in Florida that were exposed to a bloom of Karenia
      brevis (formerly Gymnodinium breve). We performed brevetoxin analysis of
      shellfish extracts and homogenates by ELISA and compared it with the mouse
      bioassay and receptor binding assay. The detection limit for brevetoxins in
      spiked oysters was 2.5 microg/100 g shellfish meat. This assay appears to be a
      useful tool for neurotoxic shellfish poisoning monitoring in shellfish and
      seawater, and for mammalian exposure diagnostics, and significantly reduces the
      time required for analyses.

PMID- 11836148
TI  - Effects of air pollutants on acute stroke mortality.
AB  - The relationship between stroke and air pollution has not been adequately
      studied. We conducted a time-series study to examine the evidence of an
      association between air pollutants and stroke over 4 years (January 1995-December
      1998) in Seoul, Korea. We used a generalized additive model to regress daily
      stroke death counts for each pollutant, controlling for seasonal and long-term
      trends and meteorologic influences, such as temperature, relative humidity, and
      barometric pressure. We observed an estimated increase of 1.5% [95% confidence
      interval (CI), 1.3-1.8%] and 2.9% (95% CI, 0.3-5.5%) in stroke mortality for each
      interquartile range increase in particulate matter < 10 microm aerodynamic
      diameter (PM(10)) and ozone concentrations in the same day. Stroke mortality also
      increased 3.1% (95% CI, 1.1-5.1%) for nitrogen dioxide, 2.9% (95% CI, 0.8-5.0%)
      for sulfur dioxide, and 4.1% (95% CI, 1.1-7.2%) for carbon monoxide in a 2-day
      lag for each interquartile range increase in single-pollutant models. When we
      examined the associations among PM(10) levels stratified by the level of gaseous
      pollutants and vice versa, we found that these pollutants are interactive with
      respect to their effects on the risk of stroke mortality. We also observed that
      the effects of PM(10) on stroke mortality differ significantly in subgroups by
      age and sex. We conclude that PM(10) and gaseous pollutants are significant risk
      factors for acute stroke death and that the elderly and women are more
      susceptible to the effect of particulate pollutants.

PMID- 11836149
TI  - Developmental increases in rat hepatic microsomal UDP-glucuronosyltransferase
      activities toward xenoestrogens and decreases during pregnancy.
AB  - Xenoestrogens, such as bisphenol A and diethylstilbestrol, are glucuronidated by
      an isoform of UDP-glucuronosyltransferase named UGT2B1 in the livers of adult
      male rats. In this study, we found that nonylphenol and octylphenol are also
      conjugated with glucuronic acid by adult rat liver microsomes. Although UDP
      glucuronosyltransferase activities toward these xenoestrogens were not detected
      in the fetal rat liver, a linear increase in enzymatic activities during neonatal
      development was observed. At 3 weeks after birth, the activities had reached the
      same level as that of adult rats. The protein and mRNA contents of UGT2B1 also
      were not detected in the fetal rat liver, but a developmental increase in newborn
      rat liver was detected by Western and Northern blotting analysis. Additionally,
      rat hepatic microsomal UDP-glucuronosyltransferase activities toward these
      xenoestrogens were reduced by about half during pregnancy of mother rats. The
      results suggest that the reproductive organs of fetal and early-stage neonatal
      rats, which are sensitive to sex hormones, face a high risk of exposure to free
      active xenoestrogens.

PMID- 11836151
TI  - Evaluation of urinary porphyrin excretion in neonates born to mothers exposed to
      airborne hexachlorobenzene.
AB  - The existence of a link between hexachlorobenzene (HCB) and porphyria cutanea
      tarda has been known for a long time. However, the epidemiologic data on effects
      on health caused by prenatal exposure have not provided convincing evidence that
      HCB alters porphyrin metabolism. Our objectives were to analyze urinary porphyrin
      excretion and HCB in maternal serum and fetal cord blood in neonates born in a
      village (Flix) near a chlorinated solvent factory, to detect possible adverse
      effects in urinary porphyrin excretion caused by prenatal exposure, and to assess
      their relationship with HCB blood levels. We conducted a cross-sectional study in
      the Porphyria Unit at a tertiary care facility in Barcelona, Spain, and the
      Pediatric Unit of the Mora d'Ebre Hospital, the reference hospital of the study
      area. We included in the study all neonates (n = 68) born in Mora d'Ebre Hospital
      1997-1999 and their mothers. We obtained 68 urine specimens of singleton neonates
      on the third day after birth to test for urinary porphyrin excretion. We obtained
      52 fetal cord blood and 56 maternal serum samples for HCB analysis. Total urinary
      porphyrins were quantified using spectrofluorometry. Porphyrin profile was
      determined by HPLC. Serum HCB was analyzed by gas chromatography coupled with
      electron capture detection. In total population, median HCB levels were 1.08
      ng/mL in cord blood and 3.31 ng/mL in maternal serum. Total urinary porphyrin
      concentration was 37.87 micromol/mol creatinine. Coproporphyrin I and
      coproporphyrin III were the major porphyrins excreted. We found no positive
      relationship between urinary porphyrin excretion and HCB levels. However, we
      observed an association between maternal smoking and coproporphyrin excretion.
      Although high environmental levels of HCB are reported in the town of Flix, we
      found no alteration in urinary porphyrin excretion.

PMID- 11836150
TI  - The challenge of preventing environmentally related disease in young children:
      community-based research in New York City.
AB  - Rates of developmental and respiratory diseases are disproportionately high in
      underserved, minority populations such as those in New York City's Washington
      Heights, Harlem, and the South Bronx. Blacks and Latinos in these neighborhoods
      represent high risk groups for asthma, adverse birth outcomes, impaired
      development, and some types of cancer. The Columbia Center for Children's
      Environmental Health in Washington Heights uses molecular epidemiologic methods
      to study the health effects of urban indoor and outdoor air pollutants on
      children, prenatally and postnatally, in a cohort of over 500 African-American
      and Dominican (originally from the Dominican Republic) mothers and newborns.
      Extensive data are collected to determine exposures to particulate matter < 2.5
      microm in aerodynamic diameter (PM(2.5)), polycyclic aromatic hydrocarbons
      (PAHs), diesel exhaust particulate (DEP), nitrogen oxide, nonpersistent
      pesticides, home allergens (dust mite, mouse, cockroach), environmental tobacco
      smoke (ETS), and lead and other metals. Biomarkers, air sampling, and clinical
      assessments are used to study the effects of these exposures on children's
      increased risk for allergic sensitization, asthma and other respiratory
      disorders, impairment of neurocognitive and behavioral development, and potential
      cancer risk. The center conducts its research and community education in
      collaboration with 10 community-based health and environmental advocacy
      organizations. This unique academic-community partnership helps to guide the
      center's research so that it is most relevant to the context of the low-income,
      minority neighborhoods in which the cohort resides, and information is delivered
      back to these communities in meaningful ways. In turn, communities become better
      equipped to relay environmental health concerns to policy makers. In this paper
      we describe the center's research and its academic-community partnership and
      present some preliminary findings.

PMID- 11836152
TI  - Do unto the biosphere what you expect others to do: a universal ethos and the
      carrying capacity of a finite planet.

PMID- 11836153
TI  - PBC-induced impairments in older adults: critique of Schantz et al's methodology
      and conclusions.

PMID- 11836155
TI  - Environmental links to early deliveries.

PMID- 11836156
TI  - Dust in the wind.

PMID- 11836157
TI  - Delitto Perfetto: foreign DNA disappears without a trace.
AB  - A group of NIEHS scientists has recently perfected a new in vivo gene
      modification technique that enables scientists to quickly generate site-directed
      mutations onto specific regions of the yeast genome. The researchers were able to
      create genetic mutations by inserting foreign DNA into host DNA without leaving a
      trace of the foreign DNA. Dubbed "Delitto Perfetto," Italian for "perfect
      murder," the new technique leaves behind no clue that foreign DNA was introduced
      to engineer the desired genetic changes. It could transform the way genetic
      researchers analyze how genes function and respond to human disease and
      environmental influences.

PMID- 11836158
TI  - Rituximab in autoimmune cytopenias: for which patients?

PMID- 11836159
TI  - Novel genes, proteins, and inherited disorders of iron overload: iron metabolism
      is less boring than thought.

PMID- 11836161
TI  - Heterozygosity of CDAN II (HEMPAS) gene may be detected by the analysis of
      erythrocyte membrane glycoconjugates from healthy carriers.
AB  - BACKGROUND AND OBJECTIVES: Congenital dyserythropoietic anemia (CDA) type I, II,
      and III, is associated with abnormalities of erythrocyte membrane glycoconjugates
      that are most pronounced in type II CDA or hereditary erythroblastic
      multinuclearity with a positive acidified-serum test (HEMPAS). The abnormalities
      consist in hypoglycosylation of polylactoaminoglycans linked to proteins (as in
      band 3 glycoprotein) and ceramides (known under the name of
      polyglycosylceramides) as well as in accumulation of some oligoglycosylceramides:
      lactotriaosylceramide, neolactotetraosylceramide, and sometimes
      globotetraosylceramide. Glycophorin A is partially unglycosylated with respect to
      O-linked glycans. Types I and II of the disease are inherited in an autosomal
      recessive fashion. The aim of the present study was to investigate a possibility
      that heterozygosity with respect to CDAN2 gene in healthy carriers could be
      detected by analysis of erythrocyte membrane glycoconjugates. DESIGN AND METHODS:
      We examined a family which consisted of heterozygous parents and their two sons,
      one of whom was afflicted with CDA II (proband) while the other was healthy. In
      all family members the glycosylation status of band 3 glycoprotein,
      polyglycosylceramides and glycophorin A was evaluated from their carbohydrate
      molar composition. In addition we determined erythrocyte membrane contents of
      oligo- and polyglycosylceramides, and agglutinability of erythrocytes by anti-i
      antibody. RESULTS: We found that the heterozygous parents showed, but about 50%
      less pronounced, most of the typical abnormalities of erythrocyte membrane
      glycoconjugates that were present in the proband. These abnormalities included:
      hypoglycosylation of band 3, accumulation and hypoglycosylation of
      polyglycosylceramides, and accumulation of lactotriaosylceramide. The level of
      neolactotetraosylceramide in the erythrocyte membranes of the parents was,
      however, normal. Globotetraosylceramide content was elevated in erythrocytes from
      the proband and, surprisingly, even more so in the parents. Glycophorin A in the
      proband was only slightly abnormal. Erythrocytes from both the parents and the
      proband expressed increased agglutinability with anti-i antibody. All
      glycoconjugates examined were normal in erythrocytes from the healthy son.
      INTERPRETATION AND CONCLUSIONS: Individuals heterozygous with respect to CDAN2
      gene can be identified through determination of the carbohydrate molar
      composition of band 3 and polyglycosylceramides as well as by an elevated
      erythrocyte content of polyglycosylceramides. In the parents these abnormalities
      show dosage effects. Determination of the carbohydrate molar composition of
      glycophorin A and of oligoglycosylceramides seems to be less promising. These
      findings indicate that the analysis of erythrocyte membrane glycoconjugates may
      be a valuable addition to the repertoire of methods used in studies on the
      genetics of CDA.

PMID- 11836160
TI  - Clinical phenotypes and molecular characterization of Hb H-Pakse disease.
AB  - BACKGROUND AND OBJECTIVES: Hemoglobin Constant Spring (Hb CS), caused by a
      termination codon mutation (TAA-->CAA) in the a2 gene, is the most common non
      deletional type of a thalassemia in Southeast Asia. This mutation can most easily
      be detected by loss of an MseI-restriction site (T/TAA) spanning the termination
      codon. Recently, we sequenced the a globin genes from patients with a thalassemia
      in whom this MseI site was absent. This revealed, a previously described
      termination codon mutation (TAA-->TAT) associated with Hb Pakse. This prompted us
      to re-evaluate the molecular basis of a thalassaemia in other Thai patients with
      non-deletional types of Hb H disease. DESIGN AND METHODS: DNA samples from 30
      patients, previously diagnosed as having Hb H-CS disease, were characterized by
      direct genomic sequencing and by using a mismatched polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP). Clinical and hematologic
      data were assessed. RESULTS: Hemoglobin electrophoresis in almost all 30
      unrelated patients with non-deletional a thalassemia revealed a slow migrating
      band resembling Hb CS. Five of these patients were found to have Hb H-Pakse
      disease and the remainder had Hb H-CS disease. Comparing the hematology in
      patients with these two genotypes, no significant differences were found except
      that the proportion of Hb H was higher in patients with Hb H-Pakse disease.
      INTERPRETATION AND CONCLUSIONS: These results suggest that termination codon
      mutations may have been previously misidentified in many cases of non-deletional
      Hb H disease. Findings from six unrelated families described in this study
      suggest that the proportion of patients with the Hb Pakse mutation might be
      underestimated and that this mutation could be prevalent in Southeast Asia.
      Analysis of mismatched-PCR-RFLP, described here, was shown to provide an
      unequivocal diagnosis and will be applicable in population screening programs.

PMID- 11836162
TI  - Prevalence of HFE genotypes, C282Y and H63D, in patients with hematologic
      disorders.
AB  - BACKGROUND AND OBJECTIVES: Iron status has implications for normal erythrocyte
      and leukocyte function and for platelet count, size and activation. Increased
      storage of iron is considered a potential risk factor participating in the
      pathogenesis of malignant diseases. Since HFE gene mutations have recently been
      implicated in unbalanced iron homeostasis, we set out to examine the prevalence
      of these mutations in patients with hematologic disorders. DESIGN AND METHODS:
      C282Y and H63D mutations were determined in 232 patients with various hematologic
      disorders treated at Oulu University Hospital between 1987 and 2000. DNA samples
      extracted from either the peripheral blood or bone marrow of these patients were
      amplified by a polymerase chain reaction (PCR) method using sequence-specific
      primers, and the products were analyzed on agarose gels. RESULTS: There was a
      slight tendency towards lower frequencies of the C282Y allele in patients with
      acute myeloid leukemia (AML) (3.8%, n=53) and higher frequencies in those with
      essential thrombocythemia (ET) (16.2%, n=37). Contrary to some expectations,
      however, the frequency of the C282Y allele in acute lymphoblastic leukemia turned
      out to be normal (7.0%, n=43). Our data showed no significant deviations in H63D
      mutation frequency in any of the categories of patients. INTERPRETATION AND
      CONCLUSIONS: Our results do not show any significant association between HFE gene
      mutations and hematologic malignancies. The divergent frequencies observed for
      the C282Y mutation in patients with AML and ET highlight the need for larger
      population studies of HFE mutations in patients with hematologic diseases.

PMID- 11836163
TI  - Co-transfection of p16(INK4a) and p53 genes into the K562 cell line inhibits cell
      proliferation.
AB  - BACKGROUND AND OBJECTIVES: The tumor suppressor genes p53 and p16(INK4a), both of
      which act in tumor surveillance, are homozygously deleted in the human leukemia
      cell line K562. This study was performed to assess whether co-transfection of the
      p16(INK4a) and p53 genes could inhibit K562 cell proliferation. DESIGN AND
      METHODS: p16(INK4a) and p53 genes were co-transfected into K562 cells with
      liposome, and the expression of the transfected genes was detected by Western
      immunoblotting and immunocytochemistry. The effect of the p16(INK4a) and p53
      transfected cell culture was quantified by trypan blue staining, and the number
      of recovered viable cells was assessed every day after transfection. Cells were
      analyzed for expression of annexin V in order to detect apoptosis.
      Differentiation of transfected K562 cells was measured by the benzidine oxidation
      test, and the cell cycle was analyzed by flow cytometry. RESULTS: After co
      transfection, there were 23% and 28% p53 and p16(INK4a) positive cells
      respectively. Co-transfection with p16(INK4a) and p53 genes significantly
      inhibited cell proliferation when compared to transfection with either p16(INK4a)
      or p53 gene. The percentage of cells expressing the apoptosis-related cell
      surface antigen annexin V was significantly higher in p53 and p16(INK4a)
      transfected cells than in p53 or p16(INK4a) transfected cells (6.24+/-0.37% vs
      4.88+/- 0.17%, p<0.05 and vs 2.78+/-0.26%, p<0.05, respectively). p16(INK4a) and
      p53 co-transfection significantly increased the number of cells in G1 phase and
      decreased that in S phase. INTERPRETATION AND CONCLUSIONS: Expression of wild
      type p16(INK4a) and p53 genes in K562 cells results in reduced proliferation and
      apoptosis. Introduction of exogenous p16(INK4a) and p53 genes into K562 cells
      might contribute to the clinical treatment of leukemia.

PMID- 11836164
TI  - Complex variant Philadelphia translocations involving the short arm of chromosome
      6 in chronic myeloid leukemia.
AB  - BACKGROUND AND OBJECTIVES: Around 5% of chronic myeloid leukemias (CML) are
      characterized by complex variant Philadelphia (Ph) translocations involving one
      or more chromosomal regions in addition to 9 and 22. The BCR/ABL1 fusion gene is
      usually found on der(22). The additional gene(s) involved in complex variant Ph
      rearrangements have not been characterized. DESIGN AND METHODS: We performed
      fluorescent in situ hybridization (FISH) in three complex variant Ph
      translocations involving the short arm of chromosome 6 in addition to 9 and 22.
      The BCR/ABL1 D-FISH probe was applied to localize the BCR/ABL1 fusion gene as
      well as the 5'ABL1 and the 3'BCR. Locus-specific probes were used to narrow the
      6p breakpoint. RESULTS: In all cases the BCR/ABL1 fusion gene was located on the
      Ph chromosome whereas the reciprocal ABL1/BCR gene was detected only in patient
      #2. On 6p, breakpoints were narrowed to three different regions: centromeric to
      the human major histocompatibility complex (MHC), between PAC 524E15 and
      PAC162J16, in the first patient, and telomeric to the MHC, between PAC 329A5 and
      PAC 145H9, and between PAC 136B1 and PAC 206F19, in the second and third
      patients, respectively. In patients #2 and 3 a chromosomal rearrangement
      different from a true complex variant was discovered. In both cases, a classical
      t(9;22) was associated with an additional translocation involving the
      der(9)t(9;22). INTERPRETATION AND CONCLUSIONS: Rearrangements at 6p in complex Ph
      aberrations involve more than one gene/locus. Classical t(9;22), masked by
      additional chromosomal rearrangements, can resemble complex variant Ph
      translocations, and can be detected only using appropriate FISH probes.

PMID- 11836165
TI  - Acute erythroid neoplastic proliferations. A biological study based on 62
      patients.
AB  - BACKGROUND AND OBJECTIVES: The terms acute erythroleukemia and AML-M6 are defined
      in the FAB classification as proliferations of dysplastic erythroid elements
      mixed with blasts of myeloid origin, but pure erythroid leukemias are not
      included. The recent WHO classification has a category of acute myeloid leukemia
      not otherwise categorized, which includes acute erythroid leukemia (M6) of two
      subtypes: M6a-erythroleukemia (erythroid/myeloid) and M6b-pure erythroid
      leukemia. The aims of this co-operative study were to discover the incidences of
      these different subtypes, and pay special attention to the morphology of these
      entities. DESIGN AND METHODS: We reviewed a series of 62 patients with erythroid
      neoplastic proliferations. Previous medical history, age, sex, peripheral blood
      and bone marrow cell counts, cytochemical stains, immunophenotype, and
      cytogenetics were evaluated at presentation. We analyzed the incidence of
      erythrocyte, leukocyte and platelet abnormalities in the peripheral blood. In
      bone marrow we analyzed dysplastic features of erythroblasts, granulocytic
      elements and the megakaryocytic lineage. RESULTS: Fifty-three patients met the
      criteria of M6a subtype of the WHO classification, and 2 were classified as
      having pure erythremia (M6b); 7 cases could not be classified according to the
      WHO criteria. Fifty-five patients presented with de novo acute leukemia, and
      seven patients had secondary acute leukemia. The most frequent dysplastic
      features in blood smears were: schistocytes, tear-drop and pincered cells in
      erythrocytes; hypogranulation and hyposegmentation in leukocytes; gigantism and
      hypogranulation in platelets. In bone marrow, megaloblastic changes,
      multinuclearity, karyorrhexis and basophilic stippling in erythroblasts;
      hypogranulation and gigantism in granulocytic series, and micromegakaryocytes and
      unconnected nuclei in megakarocytes were the most dysplastic features. A positive
      PAS reaction and increase of bone marrow iron with ring sideroblasts were common
      features. Trilineage dysplasia was present in 54% of cases. Dysplastic features
      in granulocytic elements were absent in 26% of patients and minimal
      erythroblastic dysplasia was observed in seven patients. A complex karyotype was
      seen in 27% of patients; chromosomes 5 and 7 were the most frequently involved.
      INTERPRETATION AND CONCLUSIONS: De novo acute erythroid leukemia was more
      frequent than secondary cases in our series. The most frequent type of acute
      erythroid proliferation was the WHO M6a subtype and the least the pure erythroid
      leukemia. We found a group of seven patients (11%) who could not be classified
      according to the WHO criteria. Morphologic findings of erythrocytes in peripheral
      blood, such as schistocytes, tear-drop and pincered cells, were outstanding
      features. Morphologic aspects remain one of the most important tools for
      diagnosing these entities.

PMID- 11836166
TI  - Prognostic value of karyotypic analysis in children and adults with high-risk
      acute lymphoblastic leukemia included in the PETHEMA ALL-93 trial.
AB  - BACKGROUND AND OBJECTIVES: Cytogenetic analysis is one of the most reliable
      prognostic factors in acute lymphoblastic leukemia. The objective of this study
      was to analyze the prognostic value of cytogenetic analysis in children and
      adults with high-risk acute lymphoblastic leukemia (HR-ALL) included in a
      prospective multicenter trial. DESIGN AND METHODS: One hundred and thirty
      patients (44 children and 86 adults) with HR-ALL included in the PETHEMA ALL-93
      trial had an adequate cytogenetic study after review. Cytogenetic subgroups were
      established according to the cancer and acute leukemia group B criteria
      (unfavorable: 11q23, t(9;22), -7 and +8; normal; miscellaneous: the remaining
      chromosome abnormalities) and their main clinicobiological features were
      compared. Univariable and multivariable analyses for complete remission (CR)
      attainment, event-free survival (EFS) and overall survival (OS) were performed.
      RESULTS: The mean SD age was 26 14 years. Two were infants (<1 year), 42 were
      children and 86 adults (19-50 years). The cytogenetic study was normal in 44
      (34%) cases. The most frequent chromosomal rearrangement was t(9;22)(q34;q11) (34
      cases, 26%, 30 adults), followed by 11q23 (12 cases, 9% -8 children-, including
      t(4;11)(q21;q23) in 8, 7 children). Patients with t(9;22) were older than the
      remaining cases, whereas those with 11q23 rearrangements were younger and had
      higher WBC counts. Multivariable analyses showed two associated factors in adults
      with a lower frequency of CR and a shorter EFS and OS: t(9;22) and slow response
      to therapy (assessed by a percentage of blast cells higher than 10% in bone
      marrow study on day 14). For children with very high-risk ALL, only slow response
      to therapy (assessed by the presence of blast cells in peripheral blood on day 8)
      was associated with a negative impact on CR, EFS and OS. INTERPRETATION AND
      CONCLUSIONS: In adult patients with high-risk acute lymphoblastic leukemia
      included in the PETHEMA ALL-93 protocol, cytogenetic analysis at diagnosis is a
      useful independent prognostic marker. The poorest prognosis for patients with
      t(9;22) justifies the development of specific treatments for these patients. In
      this small subgroup of children with very high-risk ALL no cytogenetic
      characteristics was found to influence the results of therapy, slow response to
      therapy being the only prognostic factor.

PMID- 11836168
TI  - Lower birth-weight in neonates of mothers carrying factor V G1691A and factor II
      A(20210) mutations.
AB  - BACKGROUND AND OBJECTIVES: Inherited thrombophilia has been associated with fetal
      and maternal complications of pregnancy. It is reasonable to suppose that an
      imbalance of maternal hemostasis could lead to decreased fetal growth. DESIGN AND
      METHODS: We retrospectively investigated the birth-weight of neonates in relation
      to the presence of factor V G1691A and factor II A(20210) mutations in the
      mothers. Overall, 755 women (194 with a history of unexplained recurrent
      pregnancy loss, 202 with gestational hypertension with or without proteinuria,
      359 with at least one uneventful pregnancy) and 1100 alive neonates were
      considered. RESULTS: Among 980 neonates from mothers without mutations, 136
      (13.9%) weighed <2500 grams, whereas 34 out 123 (27.6%) neonates from mothers
      carrying the factor V G1691A or factor II A(20210) mutation were under this birth
      weight (OR: 2.4, 95%CI: 1.5- 3.7). Adjusting for diagnosis, parity, and age, the
      risk of having a baby <2500 grams was 2.0 (95%CI: 1.1-3.6) in women carrying
      factor V G1691A or factor II A(20210) mutation. When we analyzed all the neonates
      according to growth centiles and the presence of a thrombophilic mutation in the
      mothers, we found 142 (14.5%) and 28 (22.8%) neonates under the 10th centile from
      mothers without and with thrombophilic mutations, respectively (OR: 1.7, 95%-CI:
      1.1-2.7). Adjusting for confounding variables (diagnosis, parity and age), the
      association between thrombophilic mutations and <10th growth centile did not
      change (OR: 1.7, 95% CI: 1.0-3.0). INTERPRETATION AND CONCLUSIONS: Mothers
      carrying the factor V G1691A or factor II A(20210) mutation have a significantly
      higher risk of delivering neonates with a lower birth-weight.

PMID- 11836167
TI  - Actions of the selective protein kinase C inhibitor PKC412 on B-chronic
      lymphocytic leukemia cells in vitro.
AB  - BACKGROUND AND OBJECTIVES: The staurosporine derivative PKC412 (CGP41251) is a
      more selective inhibitor of the conventional isoforms of protein kinase C (PKC)
      than is the parent compound. In addition to its growth inhibitory properties,
      PKC412 reverses the efflux function of the multidrug resistance (MDR)-1 gene
      product, P-glycoprotein (P-gp). DESIGN AND METHODS: The in vitro actions of
      PKC412 were investigated in peripheral blood lymphocytes (PBL) from 4 normal
      volunteers, B-cell isolates from 3 normal tonsils and 31 patients with B-cell
      chronic lymphocytic leukemia (B-CLL). Following incubation with PKC412 for 2
      days, the viability of B-CLL cells was decreased relative to that of controls
      (63+/-23% at 1 micromole/L; 52+/-30% at 10 micromole/L; n=20). Normal PBL were
      significantly more resistant to the drug (91+/-5% viable cells at 1 micromole/L;
      73+/-18% at 10 micromole/L; n=4). Thirteen of the B-CLL patients were treated
      with oral PKC412 in a phase II trial. RESULTS: PKC activity in malignant cells
      from these patients showed a reduction post-treatment of 25-96% of their
      respective pre-treatment levels. Morphologic analysis, as well as in situ assay
      for DNA strand breaks (TUNEL assay) showed that B-CLL cells were killed by an
      apoptotic mechanism. In B-CLL cells the mean IC50, for PKC412, as measured by the
      reduction of 3-(4,5-dimethylthiozol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT),
      was 2.1 micromol/L in 16 samples in which the IC50 were below the maximum
      concentration of PKC412 used for the assay. In tonsillar B-cells, the mean IC50
      was 11 micromol/L whereas PBL cells were resistant. Four of eight and 1/3 B-CLL
      samples that were resistant to chlorambucil and fludarabine, respectively, were
      sensitive to PKC412. In 15/31 B-CLL samples a dose-dependent reversal of P-gp
      mediated drug efflux by PKC412 was observed. A statistically significant
      correlation (p<0.001) was observed between P-gp protein expression as measured by
      FACScan analysis and the reversal of efflux activity by either PKC412 or
      verapamil. PKC412 increased the sensitivity of B-CLL cells to 2'
      chlorodeoxyadenosine and chlorambucil. INTERPRETATION AND CONCLUSIONS: This study
      establishes the in vitro cytotoxic and multidrug resistance (MDR) modulatory
      properties of PKC412 towards malignant cells from B-CLL patients. The direct
      antitumor activity combined with the potential for P-gp modulation make PKC412 an
      attractive drug for the treatment of malignancies expressing the MDR phenotype,
      or in combination with conventional drugs.

PMID- 11836169
TI  - Reduced inhibition of activated prothrombin by heparin and venous
      thromboembolism: heparin resistance revisited.
AB  - BACKGROUND AND OBJECTIVES: We evaluated a new test, based on prothrombin
      activation by Echis Carinatus snake venom in the absence/presence of
      unfractionated heparin, in patients with venous thromboembolism (VTE). DESIGN AND
      METHODS: The test (activated prothrombin heparin-inhibition test) was performed
      in 555 unselected, unrelated patients who had suffered from at least one
      objectively confirmed VTE and the results were compared with those obtained in
      408 healthy controls. RESULTS: In 71 (12.8%) of the 555 patients the results of
      the test, expressed as a normalized ratio, were below the cut-off. This compared
      with 19 (5% by definition) results below the cut-off in the control group. The
      crude OR for VTE in subjects with altered vs those with normal results was 3.00
      (95% CI: 1.78-5.07). ORs did not significantly change after adjustment for age
      (2.86, 95% CI: 1.68-4.85) and age/sex (2.80, 95% CI: 1.64-4.77) by logistic
      regression. After adjustment for antithrombin III, fibrinogen and prothrombin
      levels the risk associated with altered results remained significantly high. The
      overall OR for VTE in females (3.22; 95% CI: 1.53-6.75) was higher than that in
      males (2.69; 95% CI: 1.27-5.69). However, for both sexes there was a sharp
      increase in the risk of VTE associated with altered results in patients aged less
      than 45 years (crude OR 9.61; 95% CI: 3.38-27.3). INTERPRETATION AND CONCLUSIONS:
      Lower than expected thrombin inhibition by endogenous antithrombin action after
      full activation by heparin addition was found to be a common feature in patients
      who suffered from previous venous thrombotic events, and may reflect a hitherto
      unrecognized thrombophilic alteration.

PMID- 11836170
TI  - B-cell depletion with rituximab as treatment for immune hemolytic anemia and
      chronic thrombocytopenia.
AB  - BACKGROUND AND OBJECTIVES: Rituximab reacts specifically with the CD20 antigen
      and induces B-cell depletion. This could interfere with the production of
      autoantibodies in some immune diseases. The objective of this study was to assess
      the effects of rituximab in autoimmune hemolytic anemia and thrombocytopenia.
      DESIGN AND METHODS: Seven patients (one with cold agglutinin disease, two with
      warm antibody autoimmune hemolytic anemia, four with chronic idiopathic
      thrombocytopenic purpura) previously refractory to conventional treatments were
      treated with weekly infusions of rituximab, 375 mg/m2, for 4 weeks. Only
      treatment with steroids, if strictly necessary, was allowed during the period of
      rituximab administration, but only patients who reached steroid suspension were
      considered responders. The pharmacokinetics of rituximab were quantified during
      therapy and the follow-up period. RESULTS: All patients had marked, even if
      temporary, B-cell depletion. Three patients, 1 with cold agglutinin disease (CAD)
      and 2 with chronic idiopathic thrombocytopenic purpura (ITP), had a complete
      hematologic response. In the patient with cold agglutinin disease a decrease in
      the agglutinin titer was observed. The hematologic improvement was prompt,
      appearing by the second or third infusion of rituximab. The response duration was
      CAD 96+, ITP 17+ and 13+ weeks in these 3 patients. Treatment tolerance was
      satisfactory and no infections or other late events were registered. Serum
      rituximab concentrations appeared to be similar to those calculated in a
      historical control group of patients with follicular non-Hodgkin's lymphoma who
      received rituximab as consolidation of response after first-line CHOP
      chemotherapy. INTERPRETATION AND CONCLUSIONS: Rituximab appeared to be active and
      safe in some patients with refractory autoimmune hemolytic anemia and
      thrombocytopenia. These results, along with data from literature, suggest that
      this agent may have a therapeutic role in autoimmune diseases.

PMID- 11836172
TI  - Anti-CD20 monoclonal antibody therapy in refractory immune thrombocytopenic
      purpura.
AB  - Multiple agents have been tried in patients with refractory immune
      thrombocytopenic purpura (ITP); however, none of these stands as a clear first
      choice. We administered rituximab, 375 mg/m2 weekly x 4, to four patients with
      refractory ITP. With a median follow-up of 7 months, one patient has achieved a
      complete response, proving the possible efficacy of such a therapeutic modality
      in this context.

PMID- 11836171
TI  - Proliferate and survive: cell division cycle and apoptosis in human
      neuroblastoma.
AB  - BACKGROUND AND OBJECTIVES: Neuroblastoma is one of the most frequent childhood
      cancers and a major cause of death from neoplasias of infancy. Although a wealth
      of studies on its molecular bases have been carried out, little conclusive
      information about its origin and evolution is available. EVIDENCE AND INFORMATION
      SOURCES: Some intriguing findings have correlated neuroblastoma development with
      aberrations of two pivotal cellular processes generally altered in human cancers,
      namely cell division cycle and apoptosis. Indeed, it has been reported that
      neuroblastoma cell lines show accumulation of Id2 protein, a factor which is able
      to hamper the pRb protein antiproliferative activity. STATE OF THE ART: The
      increased Id2 is due to N-myc gene amplification and overexpression, a phenomenon
      frequently observed in neuroblastoma and an important independent negative
      marker. Moreover, neuroblastoma cells are frequently characterized by increased
      levels of survivin, an inhibitor of the apoptotic response, and by a deficiency
      of procaspase 8, a key intermediate of the programmed cell death cascade. These
      two events, probably, make neuroblastomas more resistant to programmed cell
      death. These recent findings might suggest that neuroblastoma cells have acquired
      the capability to proliferate easily and die difficultly. PERSPECTIVES: The
      mechanistic meaning of these data will be discussed in the present review.
      Moreover, we will suggest new therapeutic scenarios opened up by the described
      alterations of cell cycle and apoptosis engines.

PMID- 11836173
TI  - Peripheral blood CD38 expression predicts time to progression in B-cell chronic
      lymphocytic leukemia after first-line therapy with high-dose chlorambucil.
AB  - CD38 expression by B-cell chronic lymphocytic leukemia (B-CLL) cells has been the
      focus of several recent studies. The aim of this study was to evaluate the
      prognostic impact of CD38 expression by peripheral blood lymphocytes on
      progression-free survival after first-line therapy with high-dose chlorambucil in
      53 previously untreated patients affected by typical CD5+ CD23+ B-CLL.

PMID- 11836174
TI  - The influence of the graft monocytes in the outcome of allogeneic bone marrow
      transplantation.
AB  - The influence of graft monocytes on graft-versus-host disease (GVHD) has not yet
      been established in clinical trials. To understand this association better, we
      evaluated the influence of bone marrow graft monocytes aiming to analyze,
      primarily, the correlation with acute GVHD and chronic GVHD and, secondarily, the
      correlation with engraftment and survival.

PMID- 11836175
TI  - Absence of hepcidin gene mutations in 10 Italian patients with primary iron
      overload.
AB  - We analyzed the hepcidin gene in 10 Italian patients with hemochromatosis not
      related to C282Y, H63D or other less frequent HFE mutations, nor to Y250X in
      TFR2. The sequencing of the whole hepcidin coding region, intron-exon junctions,
      5' and partially 3'UTRs, did not reveal any alteration in the studied patients.

PMID- 11836176
TI  - Immunostaining of von Willebrand factor multimers on agarose gels and
      nitrocellulose filters.
AB  - Human von Willebrand factor (VWF) multimeric analysis is commonly performed by
      agarose gel electrophoresis, electroblotting, and immunoenzymatic staining;
      however, high molecular weight (HMW) multimers are poorly transferred on
      nitrocellulose and should be visualized by direct gel staining with radiolabeled
      anti-VWF antibody and autoradiography or luminography.

PMID- 11836177
TI  - ATRA-induced myositis in induction therapy of acute promyelocytic leukemia.

PMID- 11836179
TI  - An unusual clinical presentation of multiple myeloma with involvement of the oro
      pharynx.

PMID- 11836178
TI  - Acute leukemia of plasmablastic type as terminal phase of multiple myeloma.

PMID- 11836180
TI  - Retinoic acid syndrome: a case of massive lung consolidation.

PMID- 11836181
TI  - Simultaneous presentation of Waldenstrom's macroglobulinemia and acute myeloid
      leukemia.

PMID- 11836182
TI  - Lactic Acidosis in Non-Hodgkin's Lymphoma and response to Chemotherapy.

PMID- 11836183
TI  - Cryopreserving with increased cellular concentrations of peripheral blood
      progenitor cells: clinical results.

PMID- 11836184
TI  - Diabetic foot disease in a patient with multiple myeloma receiving thalidomide.

PMID- 11836185
TI  - A prolonged APTT in a patient with a low grade malignant NHL - a case report.

PMID- 11836186
TI  - Tuberculosis presenting as immune thrombocytopenic purpura.

PMID- 11836187
TI  - Limitations of oral busulfan in preparative regimen before hematopoietic stem
      cell transplantation.

PMID- 11836188
TI  - Paroxysmal nocturnal haemoglobinuria following breast cancer radiotherapy.

PMID- 11836189
TI  - AIDA treatment for high-risk acute promyelocytic leukemia in a pregnant woman at
      21 weeks of gestation.

PMID- 11836190
TI  - Systemic injection of GM-CSF increases survival in a murine model of acute
      leukemia.

PMID- 11836191
TI  - Role of anxiety and depression in the onset of spontaneous preterm labor.
AB  - The aim of this cohort study conducted in France in 1997-1998 was to investigate
      the effects of antenatal anxiety and depression on spontaneous preterm labor. A
      consecutive series of 634 pregnant women with singleton pregnancies was included.
      Anxiety and depression were assessed using self-administered questionnaires:
      Spielberger's State-Trait Anxiety Inventory and the Edinburgh depression scale.
      Depression scores were dichotomized with a cutoff value suggestive of major
      depression. The 75th percentile was used for anxiety scores. A logistic
      regression analysis, controlling for sociodemographic and biomedical factors and
      including interaction terms, revealed that depression was positively associated
      with the outcome among underweight women, defined as women with a prepregnancy
      body mass index below 19 (adjusted odds ratio (OR) = 6.9, 95% confidence interval
      (CI): 1.8, 26.2). A similar result was observed for trait anxiety in women with a
      history of preterm labor (adjusted OR = 4.8, 95% CI: 1.1, 20.4). The association
      was close to significance for state anxiety in women with vaginal bleeding
      (adjusted OR = 3.6, 95% CI: 0.9, 14.7). These findings show that anxiety and
      depression, when combined with specific biomedical factors, are associated with
      spontaneous preterm labor. A synergic action of psychological and biomedical
      factors on the secretion of placental corticotropin-releasing factor is
      hypothesized.

PMID- 11836192
TI  - Is preterm labor a valid endpoint in perinatal research?

PMID- 11836194
TI  - Moderate alcohol intake during pregnancy and the risk of stillbirth and death in
      the first year of life.
AB  - The authors evaluated the association between alcohol intake during pregnancy and
      risk of stillbirth and infant death in a cohort of pregnant women receiving
      routine antenatal care at Aarhus University Hospital (Aarhus, Denmark) between
      1989 and 1996. Prospective information on alcohol intake, other lifestyle
      factors, maternal characteristics, and obstetric risk factors was obtained from
      self-administered questionnaires and hospital files, and 24,768 singleton
      pregnancies were included in the analyses (116 stillbirths, 119 infant deaths).
      The risk ratio for stillbirth among women who consumed > or =5 drinks/week during
      pregnancy was 2.96 (95% confidence interval: 1.37, 6.41) as compared with women
      who consumed <1 drink/week. Adjustment for smoking habits, caffeine intake, age,
      prepregnancy body mass index, marital status, occupational status, education,
      parity, and sex of the child did not change the conclusions, nor did restriction
      of the highest intake group to women who consumed 5-14 drinks/week (risk ratio =
      3.13, 95% confidence interval: 1.45, 6.77). The rate of stillbirth due to
      fetoplacental dysfunction increased across alcohol categories, from 1.37 per
      1,000 births for women consuming <1 drink/week to 8.83 per 1,000 births for women
      consuming > or = 5 drinks/week. The increased risk could not be attributed to the
      effect of alcohol on the risk of low birth weight, preterm delivery, or
      malformations. There was little if any association between alcohol intake and
      infant death.

PMID- 11836195
TI  - Maternal serum level of 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene and risk of
      cryptorchidism, hypospadias, and polythelia among male offspring.
AB  - 1,1-Dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE) is a metabolite of the
      insecticide 2,2-bis(p-chlorophenyl)-1,1,1-trichloroethane (DDT) and is a
      ubiquitous environmental contaminant. Nearly everyone in the United States has a
      detectable serum level of DDE. DDE was recently found to inhibit binding of
      androgen to its receptor and to block androgen action in rodents. Normal
      development of male genitalia in mammals depends on androgen action. The authors
      used stored serum samples to examine the relation between maternal DDE levels
      during pregnancy and adjusted odds of cryptorchidism (n = 219), hypospadias (n =
      199), and polythelia (extra nipples) (n = 167) among male offspring, using a
      nested case-control design with one control group (n = 552). Subjects were
      selected from the Collaborative Perinatal Project, a US birth cohort study begun
      in 1959-1966, when DDE levels were much higher than they are at present. Compared
      with boys whose mother's recovery-adjusted serum DDE level was less than 21.4
      microg/liter, boys with maternal levels greater than or equal to 85.6
      microg/liter had adjusted odds ratios of 1.3 (95% confidence interval (CI): 0.7,
      2.4) for crypt-orchidism, 1.2 (95% CI: 0.6, 2.4) for hypospadias, and 1.9 (95%
      CI: 0.9, 4.0) for polythelia. For cryptorchidism and polythelia, the results were
      consistent with a modest-to-moderate association, but in no instance was the
      estimate very precise. The results were inconclusive.

PMID- 11836196
TI  - Alcohol and hepatocellular carcinoma: the effect of lifetime intake and hepatitis
      virus infections in men and women.
AB  - The authors investigated the dose-effect relation between alcohol drinking and
      hepatocellular carcinoma (HCC) in men and women separately, also considering
      hepatitis B and hepatitis C virus infections. They enrolled 464 subjects (380
      men) with a first diagnosis of HCC as cases and 824 subjects (686 men) unaffected
      by hepatic diseases as controls; all were hospitalized in Brescia, northern
      Italy, in 1995-2000. Spline regression models showed a steady linear increase in
      the odds ratio of HCC for increasing alcohol intake, for values of >60 g of
      ethanol per day, with no substantial differences between men and women. Duration
      of drinking and age at start had no effect on the odds ratio when alcohol intake
      was considered. Former drinkers who had stopped 1-10 years previously had a
      higher risk of HCC than current drinkers did. The effect of alcohol drinking was
      evident even in the absence of hepatitis B or hepatitis C virus infection. In
      addition, a synergism between alcohol drinking and either infection was found,
      with approximately a twofold increase in the odds ratio for each hepatitis virus
      infection for drinkers of >60 g per day.

PMID- 11836197
TI  - Alcohol consumption and risk of peripheral arterial disease: the Rotterdam study.
AB  - Moderate alcohol consumption is associated with a reduced risk of cardiovascular
      disease. Data on alcohol consumption and atherosclerosis are scarce. To determine
      the association between alcohol consumption and risk of peripheral arterial
      disease, the authors carried out a cross-sectional study (1990-1993) in the
      population-based Rotterdam Study among men and women aged 55 years or over. Data
      on alcohol consumption and peripheral arterial disease, as measured by the
      ankle/brachial blood pressure index, were available for 3,975 participants
      without symptomatic cardiovascular disease. Male drinkers consumed beer, wine,
      and liquor, while female drinkers consumed predominantly wine and fortified wine
      types. An inverse relation between moderate alcohol consumption and peripheral
      arterial disease was found in women but not in men. Because of residual
      confounding by smoking, analyses were repeated in nonsmokers. In nonsmoking men,
      odds ratios were 0.86 (95% confidence interval (CI): 0.46, 1.63) for daily
      alcohol consumption up to and including 10 g, 0.75 (95% CI: 0.37, 1.55) for 11-20
      g, and 0.68 (95% CI: 0.35, 1.34) for more than 20 g, compared with nondrinking.
      In nonsmoking women, corresponding odds ratios were 0.65 (95% CI: 0.48, 0.87),
      0.66 (95% CI: 0.42, 1.05), and 0.41 (95% CI: 0.21, 0.77), respectively. In
      conclusion, an inverse association between alcohol consumption and peripheral
      arterial disease was found in nonsmoking men and women.

PMID- 11836198
TI  - Endogenous estrogen exposure and cardiovascular mortality risk in postmenopausal
      women.
AB  - In this study, the authors investigated whether combined information on
      reproductive factors has additive value to the single reproductive factor age at
      menopause for assessing endogenous estrogen exposure and cardiovascular mortality
      risk in postmenopausal women. They conducted a population-based cohort study that
      included 9,450 postmenopausal women from Nijmegen, the Netherlands, who were aged
      35--65 years at enrollment in 1975, with a median follow-up of 20.5 years. A Cox
      proportional hazards model and Receiver Operating Curves were used to analyze the
      data. Women aged 52 years or more at menopause had an 18% reduction in
      cardiovascular mortality (hazard ratio = 0.82, 95% confidence interval (CI):
      0.69, 0.98) compared with those aged 44 years or less. Women with more than 18
      years of exposure to endogenous estrogen had a statistically significant 20%
      reduction in cardiovascular mortality (hazard ratio = 0.80, 95 percent CI: 0.67,
      0.96) compared with those who had 13 years of exposure or less. The area under
      the curve of the Receiver Operating Curves for the two models was identical (area
      under the curve = 0.67, 95 percent CI: 0.66, 0.68). This study shows that age at
      menopause is related to cardiovascular disease mortality and that a newly
      developed composite measure of endogenous estrogen exposure does not add to the
      predictive value of age at menopause for cardiovascular mortality.

PMID- 11836199
TI  - Ethnic differences in the association between body mass index and hypertension.
AB  - Interest in ethnicity-specific definitions of obesity has been hindered by a lack
      of data clarifying whether or not obesity-related comorbid conditions occur at
      different levels of body mass index (BMI) (weight (kg)/height (m)(2)) in
      different ethnic groups. The objective of this study was to examine ethnic
      differences in the strength of the association between BMI and hypertension.
      Cross-sectional data obtained from adults aged 30-65 years in China (1997, n =
      3,423), the Philippines (1998, n = 1,929), and the United States (1988-1994, n =
      7,957) were used. Higher BMI was associated with a higher prevalence of
      hypertension in all ethnic groups. However, at BMI levels less than 25,
      prevalence difference figures suggested a stronger association between BMI and
      hypertension in Chinese men and women but not in Filipino women, compared with
      non-Hispanic Whites. Non-Hispanic Blacks and Filipino women had a higher
      prevalence of hypertension at every level of BMI compared with non-Hispanic
      Whites and Mexican Americans. These ethnic differences in the strength of
      association between BMI and hypertension and in underlying prevalence warrant
      further investigation into the use of ethnicity-specific BMI cutoffs in clinical
      settings to more accurately identify individuals at risk from obesity.

PMID- 11836200
TI  - Relation of cigarette smoking to 25-year mortality in middle-aged men with low
      baseline serum cholesterol: the Chicago Heart Association Detection Project in
      Industry.
AB  - It has been suggested that smoking does not influence risk of cardiovascular
      diseases in populations with low serum cholesterol levels. To determine whether
      cigarette smoking is an independent risk factor among men with low levels of
      serum cholesterol, data on 25-year coronary, cardiovascular, and all-cause
      mortality for 8,816 middle-aged men screened between 1967 and 1973 by the Chicago
      Heart Association Detection Project in Industry were examined. With Cox
      multivariate proportional hazards regression, relative risks of coronary heart
      disease and cardiovascular disease mortality associated with smoking for the two
      subcohorts with favorable levels of serum total cholesterol, that is, less than
      180 and 180-199 mg/dl, were of the same magnitude as those for men with elevated
      serum cholesterol, that is, 200-239 and 240 mg/dl. In the two lower strata of
      cholesterol, the absolute risk and absolute excess risk of mortality for current
      smokers at baseline were substantially higher compared with men who never smoked,
      with all-cause death rates of 423.0 and 428.0 per 1,000 and absolute excess rates
      of 209.8 and 225.7 per 1,000. These translate to estimated shorter life
      expectancies of 5.3 and 5.7 years, respectively. Adverse effects of smoking on
      risk of coronary, cardiovascular, and all-cause mortality prevail for men with
      lower as well as higher serum cholesterol levels.

PMID- 11836201
TI  - Changing functional status in a biethnic rural population: the San Luis Valley
      Health and Aging Study.
AB  - The San Luis Valley Health and Aging Study, was designed to examine Hispanic
      versus non-Hispanic White differences in prevalence and incidence of aging
      related outcomes in a rural population (1,358 community dwellers and 75 nursing
      home residents). Data presented here were gathered between 1993 and 1997.
      Previously reported analyses identified greater prevalence of functional
      dependence in daily living activities among Hispanic elderly, especially females,
      than among non-Hispanic White elderly. This analysis explored the degree to which
      incident changes explain these patterns. Comparisons of incidence, recovery, and
      mortality rates after 22 months revealed no significant ethnic differences,
      although trends were as hypothesized: greater Hispanic incidence, lower Hispanic
      recovery rates, and less Hispanic mortality. Overall age-adjusted incidence
      (activities of daily living = 9.5; instrumental activities of daily living = 15.1
      per 100 person-years) exceeded reports from most other studies, while rates of
      recovery (activities of daily living = 14.5; instrumental activities of daily
      living = 9.9) and mortality (4.8 among community dwellers; 6.7 including nursing
      home residents) were similar to those of other reports. Patterns of new
      dependence, recovery, and mortality did not increase the previously observed
      disparity. Greater prevalent disability in the Hispanic cohort, especially in
      women, may reflect a reservoir accumulated during younger years and related to
      culture and socioeconomic status as well as to older age.

PMID- 11836202
TI  - Individual estimation of exposures to extremely low frequency magnetic fields in
      jobs commonly held by women.
AB  - Exposures to extremely low frequency (ELF) magnetic fields have not been
      documented extensively in occupations besides the work environments of electric
      or telephone utilities. A 1980-1993 study of childhood acute lymphoblastic
      leukemia (ALL) in Quebec, Canada, gathered detailed information about the
      occupations of 491 mothers of ALL cases and mothers of a similar number of
      healthy controls. This information was combined with published data on the
      intensities of ELF magnetic fields associated with sources or work environments
      to estimate ELF magnetic field exposures for a wide range of jobs commonly held
      by women. Estimated exposures for 61 job categories ranged from 0.03 to 0.68
      microT; the 25th, 50th, and 75th percentiles were 0.135, 0.17, and 0.23 microT,
      respectively. By job category, the most highly exposed jobs (>0.23 microT)
      included bakery worker, cashier, cook and kitchen worker, electronics worker,
      residential and industrial sewing machine operator, and textile machine operator.
      By work environment, the most highly exposed job categories were electronics
      worker in an assembly plant (0.70 microT) and sewing machine operators in a
      textile factory (0.68 microT) and shoe factory (0.66 microT). These results
      provide new information on expected levels of exposure in a wide range of jobs
      commonly held by women.

PMID- 11836203
TI  - Determinants of the availability and accuracy of self-reported birth weight in
      middle-aged and elderly women.
AB  - Associations have been found between birth weight and many diseases in adult
      life. In most countries, few birth records exist for older adults; therefore,
      birth weight is usually obtained by maternal recall or self-report. This study
      examined determinants of the availability and accuracy of self-report in middle
      aged and elderly women. Birth weights, recorded at the time of birth, were found
      in 1999 for a subset of 363 women participating in a long-running cancer research
      study in the United Kingdom. Questionnaires were sent to the surviving 286 women
      requesting information on their birth weight and other factors related to their
      birth family. Twenty-five percent of the 244 respondents were able to report
      their birth weight to within 4 ounces (113.4 g) of that listed in birth records,
      28% reported it inaccurately, and 47% did not know their birth weight. The most
      important factors determining the availability of self-reported birth weight were
      having a living mother and a low birth weight (< or = 6 pounds (2,722 g)). The
      most important determinants of accuracy, for those who provided a report, were
      being younger and the eldest child. Research studies relying on self-reported
      birth weight should take these factors into account.

PMID- 11836205
TI  - ZTR: a new format for DNA sequence trace data.
AB  - MOTIVATION: To produce an open and extensible file format for DNA trace data
      which produces compact files suitable for large-scale storage and efficient use
      of internet bandwidth. RESULTS: We have created an extensible format named ZTR.
      For a set of data taken from an ABI-3700 the ZTR format produces trace files
      which require 61.6% of the disk space used by gzipped SCFv3, and which can be
      written and read at greater speed. The compression algorithms used for the trace
      amplitudes are used within the National Center for Biotechnology Information
      (NCBI) trace archive. lmb.cam.ac.uk/pub/staden/io_lib/test_data.

PMID- 11836206
TI  - A fast top-down method for constructing reliable radiation hybrid frameworks.
AB  - MOTIVATION: Radiation Hybrid Mapping (RHM) is a technique used to order a set of
      markers on a genome and estimating physical distances between them. RHM provides
      information on marker placement independent from other methods such as
      sequencing, and can therefore be used for example in genome sequencing to help
      ordering contigs. A radiation hybrid framework can be constructed by choosing a
      set of markers so that the chromosome coverage is good and so that the markers
      can be ordered with high confidence. Automatically constructing RHM frameworks is
      a computationally challenging problem. RESULTS: We have developed a new method
      for constructing radiation hybrid frameworks. Given a relatively large set of
      markers for a chromosome, the algorithm aims to select an ordered subset that
      makes up a framework, and that contains as many markers as possible. The
      algorithm has a time complexity that is better than any of the existing methods
      that we are aware of. Furthermore, we propose a method for comparing if two
      frameworks are consistent, giving a visual presentation as well as quantitative
      measures of how well the two frameworks agree. Applying our method on marker sets
      from 22 human chromosomes and comparing the resulting frameworks with previously
      published frameworks, we demonstrate that our automatic method efficiently
      constructs frameworks with good coverage of each chromosome and with high degree
      of agreement on the marker ordering.

PMID- 11836207
TI  - A Bayesian framework for combining gene predictions.
AB  - MOTIVATION: Gene identification and gene discovery in new genomic sequences is
      one of the most timely computational questions addressed by bioinformatics
      scientists. This computational research has resulted in several systems that have
      been used successfully in many whole-genome analysis projects. As the number of
      such systems grows the need for a rigorous way to combine the predictions becomes
      more essential. RESULTS: In this paper we provide a Bayesian network framework
      for combining gene predictions from multiple systems. The framework allows us to
      treat the problem as combining the advice of multiple experts. Previous work in
      the area used relatively simple ideas such as majority voting. We introduce, for
      the first time, the use of hidden input/output Markov models for combining gene
      predictions. We apply the framework to the analysis of the Adh region in
      Drosophila that has been carefully studied in the context of gene finding and
      used as a basis for the GASP competition. The main challenge in combination of
      gene prediction programs is the fact that the systems are relying on similar
      features such as cod on usage and as a result the predictions are often
      correlated. We show that our approach is promising to improve the prediction
      accuracy and provides a systematic and flexible framework for incorporating
      multiple sources of evidence into gene prediction systems.

PMID- 11836208
TI  - PlantSat: a specialized database for plant satellite repeats.
AB  - MOTIVATION: Tandemly organized repetitive sequences (satellite DNA) are
      widespread in complex eukaryotic genomes. In plants, satellite repeats often
      represent a substantial part of nuclear DNA but only a little is known about the
      molecular mechanisms of their amplification and their possible role(s) in genome
      evolution and function. Unfortunately, addressing these questions via
      characterization of general sequence properties of known satellite repeats has
      been hindered by a difficulty in obtaining a complete and unbiased set of
      sequence data for this analysis. This is mainly due to the presence of multiple
      entries of homologous sequences and of single entries that contain more than one
      repeated unit (monomer) in the public databases. RESULTS: We have established a
      computer database specialized for plant satellite repeats (PlantSat) that
      integrates sequence data available from various resources with supplementary
      information including repeat consensus sequences, abundances, and chromosomal
      localizations. The sequences are stored as individual repeat monomers grouped
      into families, which simplifies their computer analysis and makes it more
      accurate. Using this feature, we have performed a basic sequence analysis of the
      whole set of plant satellite repeats with respect to their monomer length and
      nucleotide composition. The analysis revealed several preferred length ranges of
      the monomers (approximately 165 bp and its multiples) and an over-representation
      of the AA/TT dinucleotide in the repeats. We have also detected an enrichment of
      satellite DNA sequences for the motif CAAAA that is supposed to be involved in
      breakage-reunion of repeated sequences.

PMID- 11836209
TI  - Calculating the SNP-effective sample size from an alignment.
AB  - MOTIVATION: The number of Single Nucleotide Polymorphisms (SNPs) detectable in an
      alignment is a function of the length and the number of the aligned sequences.
      The latter is called sample size. However, a typical alignment, for instance
      obtained as a BLAST-search result of a query sequence against an EST database,
      does not evenly cover the query sequence. Therefore, it is usually not clear what
      the actual sample size is. RESULTS: We present a method to calculate the
      effective sample size, called n(eff), for a given BLAST alignment. This method
      takes into account that multiple coverage contributes only logarithmically to the
      SNP yield of a given sequence stretch. We show that the effective sample size
      n(eff) is usually much smaller than would be expected for a given amount of
      coverage and illustrate this with two typical examples.

PMID- 11836210
TI  - Tumor classification by partial least squares using microarray gene expression
      data.
AB  - MOTIVATION: One important application of gene expression microarray data is
      classification of samples into categories, such as the type of tumor. The use of
      microarrays allows simultaneous monitoring of thousands of genes expressions per
      sample. This ability to measure gene expression en masse has resulted in data
      with the number of variables p(genes) far exceeding the number of samples N.
      Standard statistical methodologies in classification and prediction do not work
      well or even at all when N < p. Modification of existing statistical
      methodologies or development of new methodologies is needed for the analysis of
      microarray data. RESULTS: We propose a novel analysis procedure for classifying
      (predicting) human tumor samples based on microarray gene expressions. This
      procedure involves dimension reduction using Partial Least Squares (PLS) and
      classification using Logistic Discrimination (LD) and Quadratic Discriminant
      Analysis (QDA). We compare PLS to the well known dimension reduction method of
      Principal Components Analysis (PCA). Under many circumstances PLS proves
      superior; we illustrate a condition when PCA particularly fails to predict well
      relative to PLS. The proposed methods were applied to five different microarray
      data sets involving various human tumor samples: (1) normal versus ovarian tumor;
      (2) Acute Myeloid Leukemia (AML) versus Acute Lymphoblastic Leukemia (ALL); (3)
      Diffuse Large B-cell Lymphoma (DLBCLL) versus B-cell Chronic Lymphocytic Leukemia
      (BCLL); (4) normal versus colon tumor; and (5) Non-Small-Cell-Lung-Carcinoma
      (NSCLC) versus renal samples. Stability of classification results and methods
      were further assessed by re-randomization studies.

PMID- 11836211
TI  - Linear modes of gene expression determined by independent component analysis.
AB  - MOTIVATION: The expression of genes is controlled by specific combinations of
      cellular variables. We applied Independent Component Analysis (ICA) to gene
      expression data, deriving a linear model based on hidden variables, which we term
      'expression modes'. The expression of each gene is a linear function of the
      expression modes, where, according to the ICA model, the linear influences of
      different modes show a minimal statistical dependence, and their distributions
      deviate sharply from the normal distribution. RESULTS: Studying cell cycle
      related gene expression in yeast, we found that the dominant expression modes
      could be related to distinct biological functions, such as phases of the cell
      cycle or the mating response. Analysis of human lymphocytes revealed modes that
      were related to characteristic differences between cell types. With both data
      sets, the linear influences of the dominant modes showed distributions with large
      tails, indicating the existence of specifically up- and downregulated target
      genes. The expression modes and their influences can be used to visualize the
      samples and genes in low-dimensional spaces. A projection to expression modes
      helps to highlight particular biological functions, to reduce noise, and to
      compress the data in a biologically sensible way.

PMID- 11836212
TI  - Extracting transcriptional events from temporal gene expression patterns during
      Dictyostelium development.
AB  - MOTIVATION: The DNA microarray technology can generate a large amount of data
      describing the time-course of gene expression. These data, when properly
      interpreted, can yield a great deal of information concerning differential gene
      expression during development. Much current effort in bioinformatics has been
      devoted to the analysis of gene expression data, usually via some 'clustering
      analysis' on the raw data in some abstract high dimensional space. Here, we
      describe a method where we first 'process' the raw time-course data using a
      simple biologically based kinetic model of gene expression. This allows us to
      reduce the vast data to a few vital attributes characterizing each expression
      profile, e.g. the times of the onset and cessation of the expression of the
      developmentally regulated genes. These vital attributes can then be trivially
      clustered by visual inspection to reveal biologically significant effects.
      RESULTS: We have applied this approach to microarray expression data from samples
      isolated every 2 h throughout the 24 h developmental program of Dictyostelium
      discoideum. mRNA accumulation patterns for 50 developmental genes were found to
      fit the kinetic model with a p-value of 0.05 or better. Transcription of these
      genes appears to be initiated in bursts at well-defined periods during
      development, in a manner suggestive of a dependent sequence. This approach can be
      applied to analyses of other temporal gene expression patterns, including those
      of the cell cycle.

PMID- 11836213
TI  - Discrete simulation of regulatory homo- and heterodimerization in the apoptosis
      effector phase.
AB  - MOTIVATION: Quantitative simulation of molecular reaction networks is among the
      most promising approaches towards an understanding of complex biochemical
      pathways. Numerous qualitative as well as quantitative data from diverse
      experimental settings, in particular from genomics and proteomics, have to be
      contextually linked to convert static data into dynamic functionality. RESULTS:
      This paper presents the Lattice Molecular Automaton, a Cellular Automaton-based
      simulation tool, capable of representing complex molecular dynamics at different
      levels of granularity. A data structure concept represents molecular units, whose
      dynamics, embedded on a 2D grid, is defined via detailed intermolecular
      interaction profiles. The data structures hold diverse information as molecular
      type, potential, as well as kinetic energy states, which allows a precise
      representation of intracellular reaction networks. The molecular dynamics is
      performed via local computation of individual molecular states on the lattice,
      which, in conjunction with discretized space and time, enables excellent
      scalability of this simulation concept. This paper finally gives Lattice
      Molecular Automaton simulation results on key elements of apoptosis, the cell
      death cascade, in particular focusing on the regulatory function of homo- and
      heterodimerization of members of the Bcl-2 protein family in the apoptosis
      effector phase. The regulatory proteins Bcl2, Bax, and Bak constitute a diffusion
      driven molecular switch with inherent damping of apoptosis induction, thereby
      controlling the apoptosis reaction cascade under noisy, external apoptosis
      inducing conditions.

PMID- 11836214
TI  - Tolerating some redundancy significantly speeds up clustering of large protein
      databases.
AB  - MOTIVATION: Sequence clustering replaces groups of similar sequences in a
      database with single representatives. Clustering large protein databases like the
      NCBI Non-Redundant database (NR) using even the best currently available
      clustering algorithms is very time-consuming and only practical at relatively
      high sequence identity thresholds. Our previous program, CD-HI, clustered NR at
      90% identity in approximately 1 h and at 75% identity in approximately 1 day on a
      1 GHz Linux PC (Li et al., Bioinformatics, 17, 282, 2001); however even faster
      clustering speed is needed because the size of protein databases are rapidly
      growing and many applications desire a lower attainable thresholds. RESULTS: For
      our previous algorithm (CD-HI), we have employed short-word filters to speed up
      the clustering. In this paper, we show that tolerating some redundancy makes for
      more efficient use of these short-word filters and increases the program's speed
      100 times. Our new program implements this technique and clusters NR at 70%
      identity within 2 h, and at 50% identity in approximately 5 days. Although some
      redundancy is present after clustering, our new program's results only differ
      from our previous program's by less than 0.4%.

PMID- 11836215
TI  - Improved database searches for orthologous sequences by conditioning on outgroup
      sequences.
AB  - MOTIVATION: Searches of biological sequence databases are usually focussed on
      distinguishing significant from random matches. However, the increasing abundance
      of related sequences on databases present a second challenge: to distinguish the
      evolutionarily most closely related sequences (often orthologues) from more
      distantly related homologues. This is particularly important when searching a
      database of partial sequences, where short orthologous sequences from a non
      conserved region will score much more poorly than non-orthologous (outgroup)
      sequences from a conserved region. RESULTS: Such inferences are shown to be
      improved by conditioning the search results on the scores of an outgroup
      sequence. The log-odds score for each target sequence identified on the database
      has the log-odds score of the outgroup sequence subtracted from it. A test group
      of Caenorhabditis elegans kinase sequences and their identified C.elegans
      outgroups were searched against a test database of human Expressed Sequence Tag
      (EST) sequences, where the sets of true target sequences were known in advance.
      The outgroup conditioned method was shown to identify 58% more true positives
      ahead of the first false positive, compared to the straightforward search without
      an outgroup. A test dataset of 151 proteins drawn from the C.elegans genome,
      where the putative 'outgroup' was assigned automatically, similarly found 50%
      more true positives using outgroup conditioning. Thus, outgroup conditioning
      provides a means to improve the results of database searching with little
      increase in the search computation time.

PMID- 11836216
TI  - Automated ortholog inference from phylogenetic trees and calculation of orthology
      reliability.
AB  - MOTIVATION: Orthologous proteins in different species are likely to have similar
      biochemical function and biological role. When annotating a newly sequenced
      genome by sequence homology, the most precise and reliable functional information
      can thus be derived from orthologs in other species. A standard method of finding
      orthologs is to compare the sequence tree with the species tree. However, since
      the topology of phylogenetic tree is not always reliable one might get incorrect
      assignments. RESULTS: Here we present a novel method that resolves this problem
      by analyzing a set of bootstrap trees instead of the optimal tree. The frequency
      of orthology assignments in the bootstrap trees can be interpreted as a support
      value for the possible orthology of the sequences. Our method is efficient enough
      to analyze data in the scale of whole genomes. It is implemented in Java and
      calculates orthology support levels for all pairwise combinations of homologous
      sequences of two species. The method was tested on simulated datasets and on real
      data of homologous proteins.

PMID- 11836217
TI  - Integrated gene and species phylogenies from unaligned whole genome protein
      sequences.
AB  - MOTIVATION: Most molecular phylogenies are based on sequence alignments.
      Consequently, they fail to account for modes of sequence evolution that involve
      frequent insertions or deletions. Here we present a method for generating
      accurate gene and species phylogenies from whole genome sequence that makes use
      of short character string matches not placed within explicit alignments. In this
      work, the singular value decomposition of a sparse tetrapeptide frequency matrix
      is used to represent the proteins of organisms uniquely and precisely as vectors
      in a high-dimensional space. Vectors of this kind can be used to calculate
      pairwise distance values based on the angle separating the vectors, and the
      resulting distance values can be used to generate phylogenetic trees. Protein
      trees so derived can be examined directly for homologous sequences.
      Alternatively, vectors defining each of the proteins within an organism can be
      summed to provide a vector representation of the organism, which is then used to
      generate species trees. RESULTS: Using a large mitochondrial genome dataset, we
      have produced species trees that are largely in agreement with previously
      published trees based on the analysis of identical datasets using different
      methods. These trees also agree well with currently accepted phylogenetic theory.
      In principle, our method could be used to compare much larger bacterial or
      nuclear genomes in full molecular detail, ultimately allowing accurate gene and
      species relationships to be derived from a comprehensive comparison of complete
      genomes. In contrast to phylogenetic methods based on alignments, sequences that
      evolve by relative insertion or deletion would tend to remain recognizably
      similar.

PMID- 11836218
TI  - TreeWiz: interactive exploration of huge trees.
AB  - MOTIVATION: The rapidly increasing amount and disparity of biological data
      requires interpretation at many levels of description. Human judgement and
      intuition are important because not all data can be automatically and
      comprehensively analyzed. Visualization of trees and substructures corresponding
      to certain features are often used to analyze phylogenies or taxonomies.
      Unfortunately, most existing tools do not cope with the size of current datasets,
      the required functionality, or both. RESULTS: We introduce a program for
      visualization of huge trees and also for the interactive exploration of their
      content. We have developed a range of new schemes which are tailored for
      biological problems. Users can get an overview, zoom in, filter out data and
      retrieve details from standard databases such as SWISS-PROT. Furthermore, it is
      possible to analyze the relationship between chosen leaf sets that are specified
      by common features on a second level of representation. On a PC (with
      approximately equal to 512 MB RAM), trees of up to several tens of thousands of
      leaves can be loaded and both rapidly and interactively explored. We demonstrate
      the use of this program for the analysis of the SYSTERS data set (which contains
      hierarchically clustered protein sequences) to which PFAM domains were added as
      features.

PMID- 11836219
TI  - A viral sampling design for testing the molecular clock and for estimating
      evolutionary rates and divergence times.
AB  - MOTIVATION: The high pace of viral sequence change means that variation in the
      times at which sequences are sampled can have a profound effect both on the
      ability to detect trends over time in evolutionary rates and on the power to
      reject the Molecular Clock Hypothesis (MCH). Trends in viral evolutionary rates
      are of particular interest because their detection may allow connections to be
      established between a patient's treatment or condition and the process of
      evolution. Variation in sequence isolation times also impacts the uncertainty
      associated with estimates of divergence times and evolutionary rates. Variation
      in isolation times can be intentionally adjusted to increase the power of
      hypothesis tests and to reduce the uncertainty of evolutionary parameter
      estimates, but this fact has received little previous attention. RESULTS: We
      provide approximations for the power to reject the MCH when the alternative is
      that rates change in a linear fashion over time and when the alternative is that
      rates differ randomly among branches. In addition, we approximate the standard
      deviation of estimated evolutionary rates and divergence times. We illustrate how
      these approximations can be exploited to determine which viral sample to sequence
      when samples representing different dates are available.

PMID- 11836220
TI  - PathFinder: reconstruction and dynamic visualization of metabolic pathways.
AB  - MOTIVATION: Beyond methods for a gene-wise annotation and analysis of sequenced
      genomes new automated methods for functional analysis on a higher level are
      needed. The identification of realized metabolic pathways provides valuable
      information on gene expression and regulation. Detection of incomplete pathways
      helps to improve a constantly evolving genome annotation or discover alternative
      biochemical pathways. To utilize automated genome analysis on the level of
      metabolic pathways new methods for the dynamic representation and visualization
      of pathways are needed. RESULTS: PathFinder is a tool for the dynamic
      visualization of metabolic pathways based on annotation data. Pathways are
      represented as directed acyclic graphs, graph layout algorithms accomplish the
      dynamic drawing and visualization of the metabolic maps. A more detailed analysis
      of the input data on the level of biochemical pathways helps to identify genes
      and detect improper parts of annotations. As an Relational Database Management
      System (RDBMS) based internet application PathFinder reads a list of EC-numbers
      or a given annotation in EMBL- or Genbank-format and dynamically generates
      pathway graphs.

PMID- 11836221
TI  - The Binding Database: data management and interface design.
AB  - MOTIVATION: The large and growing body of experimental data on biomolecular
      binding is of enormous value in developing a deeper understanding of molecular
      biology, in developing new therapeutics, and in various molecular design
      applications. However, most of these data are found only in the published
      literature and are therefore difficult to access and use. No existing public
      database has focused on measured binding affinities and has provided query
      capabilities that include chemical structure and sequence homology searches.
      METHODS & RESULTS: We have created Binding DataBase (BindingDB), a public, web
      accessible database of measured binding affinities. BindingDB is based upon a
      relational data specification for describing binding measurements via Isothermal
      Titration Calorimetry (ITC) and enzyme inhibition. A corresponding XML Document
      Type Definition (DTD) is used to create and parse intermediate files during the
      on-line deposition process and will also be used for data interchange, including
      collection of data from other sources. The on-line query interface, which is
      constructed with Java Servlet technology, supports standard SQL queries as well
      as searches for molecules by chemical structure and sequence homology. The on
      line deposition interface uses Java Server Pages and JavaBean objects to generate
      dynamic HTML and to store intermediate results. The resulting data resource
      provides a range of functionality with brisk response-times, and lends itself
      well to continued development and enhancement.

PMID- 11836222
TI  - Concept and prototype of protein-ligand docking simulator with force feedback
      technology.
AB  - A novel concept for a protein-ligand docking simulator using Virtual Reality (VR)
      technologies, in particular the tactile sense technology, was designed and a
      prototype was developed. Most conventional docking simulators are based on
      numerical differential calculations of the total energy between a protein and a
      ligand. However, the basic concept of our method differs from that of
      conventional simulators. Our design utilizes the force between a ligand and a
      protein instead of the total energy. The most characteristic function of the
      system is its ability to enable the user to 'touch' and sense the electrostatic
      potential field of a protein molecule. The user can scan the surface of a protein
      using a globular probe, which is given an electrostatic charge, and is controlled
      by a force feedback device. The electrostatic force between the protein and the
      probe is calculated in real time and immediately fed back into the force feedback
      device. The user can easily search interactively for positions where the probe is
      strongly attracted to the force field. Such positions can be regarded as
      candidate sites where functional groups of ligands corresponding to the probe can
      bind to the target protein. Certain limitations remain; for example, only twenty
      protein atoms can be used to generate the electrostatic field. Furthermore, the
      system can only use globular probes, preventing drug molecules or small chemical
      groups from being simulated. These limitations are the result of our insufficient
      computer resources. However, our prototype system has the potential to become a
      novel application method as well as being applicable to conventional VR
      technologies, especially to force feedback technologies.

PMID- 11836223
TI  - Classifying G-protein coupled receptors with support vector machines.
AB  - MOTIVATION: The enormous amount of protein sequence data uncovered by genome
      research has increased the demand for computer software that can automate the
      recognition of new proteins. We discuss the relative merits of various automated
      methods for recognizing G-Protein Coupled Receptors (GPCRs), a superfamily of
      cell membrane proteins. GPCRs are found in a wide range of organisms and are
      central to a cellular signalling network that regulates many basic physiological
      processes. They are the focus of a significant amount of current pharmaceutical
      research because they play a key role in many diseases. However, their tertiary
      structures remain largely unsolved. The methods described in this paper use only
      primary sequence information to make their predictions. We compare a simple
      nearest neighbor approach (BLAST), methods based on multiple alignments generated
      by a statistical profile Hidden Markov Model (HMM), and methods, including
      Support Vector Machines (SVMs), that transform protein sequences into fixed
      length feature vectors. RESULTS: The last is the most computationally expensive
      method, but our experiments show that, for those interested in annotation-quality
      classification, the results are worth the effort. In two-fold cross-validation
      experiments testing recognition of GPCR subfamilies that bind a specific ligand
      (such as a histamine molecule), the errors per sequence at the Minimum Error
      Point (MEP) were 13.7% for multi-class SVMs, 17.1% for our SVMtree method of
      hierarchical multi-class SVM classification, 25.5% for BLAST, 30% for profile
      HMMs, and 49% for classification based on nearest neighbor feature vector Kernel
      Nearest Neighbor (kernNN). The percentage of true positives recognized before the
      first false positive was 65% for both SVM methods, 13% for BLAST, 5% for profile
      HMMs and 4% for kernNN.

PMID- 11836224
TI  - Machine learning of functional class from phenotype data.
AB  - MOTIVATION: Mutant phenotype growth experiments are an important novel source of
      functional genomics data which have received little attention in bioinformatics.
      We applied supervised machine learning to the problem of using phenotype data to
      predict the functional class of Open Reading Frames (ORFs) in Saccaromyces
      cerevisiae. Three sources of data were used: TRansposon-Insertion Phenotypes,
      Localization and Expression in Saccharomyces (TRIPLES), European Functional
      Analysis Network (EUROFAN) and Munich Information Center for Protein Sequences
      (MIPS). The analysis of the data presented a number of challenges to machine
      learning: multi-class labels, a large number of sparsely populated classes, the
      need to learn a set of accurate rules (not a complete classification), and a very
      large amount of missing values. We modified the algorithm C4.5 to deal with these
      problems. RESULTS: Rules were learnt which are accurate and biologically
      meaningful. The rules predict function of 83 ORFs of unknown function at an
      estimated accuracy of > or = 80%.

PMID- 11836225
TI  - Prediction of 3D neighbours of molecular surface patches in proteins by
      artificial neural networks.
AB  - MOTIVATION: Molecular Surface Patches (MSPs) of proteins are responsible for
      selective interactions between internal parts of one protein molecule or between
      protein and other molecules. The prediction of the neighbours of a distinct
      Secondary Structural Element (SSE) would be an important step for protein
      structure prediction. RESULTS: Based on a computational analysis of complementary
      molecular patches of SSEs, feed-forward Neural Networks (NNs) are trained on a
      large set of helices for predicting the neighbours of given MSPs. Accuracy of
      prediction is 96% if only two types of neighbours: solvent or protein are
      considered, yet drops to 81% for three types of neighbours: (1) solvent, (2)
      helix/strand or (3) coil. Implications of the method for the prediction of
      protein structure and subunit interaction are discussed. As a special test case,
      the structurally equivalent helices of monomeric myoglobin and the homologous
      subunits of tetrameric haemoglobin are compared.

PMID- 11836226
TI  - SACS--self-maintaining database of antibody crystal structure information.
AB  - MOTIVATION: The rapid increase in the number of structures in the Protein
      Databank (PDB) makes it difficult to find all structures in a given protein
      class. Automatically-maintained web-based summaries are one solution to this
      problem. RESULTS: Summary of Antibody Crystal Structures (SACS), a self
      maintaining web-site containing summary information on antibody structures in the
      PDB, is described. Mirrored PDB data are processed automatically using a Make
      based system to identify new antibody structures. The PDB header records and
      sequence data are then parsed to identify a number of features of the structure
      and the data are stored using eXtensible Markup Language (XML). eXtensible
      Stylesheet Language: Transformations (XSLT), a new style sheet language for XML,
      is used to generate Hypertext Markup Language (HTML) pages containing either a
      one-line summary of every structure or a more detailed page describing a single
      antibody.

PMID- 11836227
TI  - Association of nucleotide patterns with gene function classes: application to
      human 3' untranslated sequences.
AB  - MOTIVATION: Gene expression is dependent on two main types of signals; one
      involving transcription factors which initiates gene transcription, and another
      which regulates the translation of a nascent mRNA. These post-transcriptional
      events play an important yet incompletely understood role in regulating gene
      expression and cellular behavior. Many of the identified cis acting elements for
      translational regulation occur within the 3'untranslated region (3' UTR), and
      some have been observed to occur with surprising regularity within certain
      protein function classes. RESULTS: In this study, we present a new association
      rule mining method for discovering nucleotide sequence patterns that appear in
      more sequences than expected within protein function classes. The method is
      applied to a database of human 3' UTR sequences, and some significant
      associations between nucleotide patterns and protein function classes are
      discovered. Among previously identified patterns, the AU-Rich Element (ARE) is
      found here to occur within the 3' UTR of cytokines, providing statistical
      validation of an association often reported in the literature. The method has
      also identified some GC-rich patterns, found to occur within the 3' UTR of
      homeodomain transcription factors and nuclear proteins. The method should be
      applicable to many types of regulatory element discovery.

PMID- 11836228
TI  - Physics-based gene identification: proof of concept for Plasmodium falciparum.
AB  - The ab initio prediction of new genes in eukaryotic genomes represents a
      difficult task, notably for the identification of complex split genes. A Physics
      Based Gene Identification (PBGI) method was formulated recently (Yeramian, Gene,
      255, 139-150, 151-168, 2000a,b) to address this problem, taking as a model the
      Plasmodium falciparum genome. Here, the predictive power of this method is put
      under experimental test for this genome. The presented results demonstrate the
      usefulness of the PBGI as a gene-identification tool for P. falciparum, notably
      for the discovery of new genes with no homology to known genes. Perspectives
      opened by this new method for other eukaryotic genomes are also mentioned.

PMID- 11836229
TI  - Trev: a DNA trace editor and viewer.
AB  - Trev is a DNA trace editor and viewer, which is available free for UNIX and
      Microsoft Windows platforms. It can read all the commonly used file formats,
      including the new, compact ZTR files.

PMID- 11836230
TI  - Locating probable genes using Fourier transform approach.
AB  - FTG is a web server for analyzing nucleotide sequences to predict the genes using
      Fourier transform techniques. This server implements the existing Fourier
      transform algorithms for gene prediction and allows the rapid visualization of
      analysis by output in GIF format.

PMID- 11836231
TI  - Dragon Promoter Finder: recognition of vertebrate RNA polymerase II promoters.
AB  - Dragon Promoter Finder (DPF) locates RNA polymerase II promoters in DNA sequences
      of vertebrates by predicting Transcription Start Site (TSS) positions. DPF's
      algorithm uses sensors for three functional regions (promoters, exons and
      introns) and an Artificial Neural Network (ANN). Results on a large and diverse
      evaluation set indicate that DPF exhibits a superior predicting ability for TSS
      location compared to three other promoter-finding programs.

PMID- 11836233
TI  - Using biplots to interpret gene expression patterns in plants.
AB  - Plant biologists in fields of ecology, evolution, genetics and breeding
      frequently use multivariate methods. This paper illustrates Principal Component
      Analysis (PCA) and Gabriel's biplot as applied to microarray expression data from
      plant pathology experiments.

PMID- 11836232
TI  - LigBase: a database of families of aligned ligand binding sites in known protein
      sequences and structures.
AB  - A database comprising all ligand-binding sites of known structure aligned with
      all related protein sequences and structures is described. Currently, the
      database contains approximately 50000 ligand-binding sites for small molecules
      found in the Protein Data Bank (PDB). The structure-structure alignments are
      obtained by the Combinatorial Extension (CE) program (Shindyalov and Bourne,
      Protein Eng., 11, 739-747, 1998) and sequence-structure alignments are extracted
      from the ModBase database of comparative protein structure models for all known
      protein sequences (Sanchez et al., Nucleic Acids Res., 28, 250-253, 2000). It is
      possible to search for binding sites in LigBase by a variety of criteria. LigBase
      reports summarize ligand data including relevant structural information from the
      PDB file, such as ligand type and size, and contain links to all related protein
      sequences in the TrEMBL database. Residues in the binding sites are graphically
      depicted for comparison with other structurally defined family members. LigBase
      provides a resource for the analysis of families of related binding sites.

PMID- 11836234
TI  - CIT: identification of differentially expressed clusters of genes from microarray
      data.
AB  - Cluster Identification Tool (CIT) is a microarray analysis program that
      identifies differentially expressed genes. Following division of experimental
      samples based on a parameter of interest, CIT uses a statistical discrimination
      metric and permutation analysis to identify clusters of genes or individual genes
      that best differentiate between the experimental groups. CIT integrates with the
      freely available CLUSTER and TREEVIEW programs to form a more complete microarray
      analysis package.

PMID- 11836235
TI  - Genesis: cluster analysis of microarray data.
AB  - A versatile, platform independent and easy to use Java suite for large-scale gene
      expression analysis was developed. Genesis integrates various tools for
      microarray data analysis such as filters, normalization and visualization tools,
      distance measures as well as common clustering algorithms including hierarchical
      clustering, self-organizing maps, k-means, principal component analysis, and
      support vector machines. The results of the clustering are transparent across all
      implemented methods and enable the analysis of the outcome of different
      algorithms and parameters. Additionally, mapping of gene expression data onto
      chromosomal sequences was implemented to enhance promoter analysis and
      investigation of transcriptional control mechanisms.

PMID- 11836236
TI  - PCSB--a program collection for structural biology and biophysical chemistry.
AB  - We present the first package of Java classes specifically aimed at the handling
      of structural and biophysical problems. To enable object-oriented programming a
      basis of fundamental Java classes is required which deals with basic operations
      of vectors, matrices, amino acid sequences, crystal symmetries and PDB files.
      Five classes, which carry out these basic operations, were constructed and
      bundled together with several utility functions in the PCSB package. Furthermore,
      to demonstrate their applicability and to obtain programs handling common tasks
      in structural laboratories, we present the first six applications of PCSB. All
      applications are portable to different platforms and require only the Java
      Runtime Environment to be installed on the system. available as PDF file.

PMID- 11836237
TI  - DICHROWEB: an interactive website for the analysis of protein secondary structure
      from circular dichroism spectra.
AB  - A user-friendly website for the analysis of protein secondary structures from
      Circular Dichroism (CD) and Synchrotron Radiation Circular Dichroism (SRCD)
      spectra has been created.

PMID- 11836238
TI  - Geno3D: automatic comparative molecular modelling of protein.
AB  - Geno3D (http://geno3d-pbil.ibcp.fr) is an automatic web server for protein
      molecular modelling. Starting with a query protein sequence, the server performs
      the homology modelling in six successive steps: (i) identify homologous proteins
      with known 3D structures by using PSI-BLAST; (ii) provide the user all potential
      templates through a very convenient user interface for target selection; (iii)
      perform the alignment of both query and subject sequences; (iv) extract
      geometrical restraints (dihedral angles and distances) for corresponding atoms
      between the query and the template; (v) perform the 3D construction of the
      protein by using a distance geometry approach and (vi) finally send the results
      by e-mail to the user.

PMID- 11836239
TI  - Symmetry observations in long nucleotide sequences: a commentary on the Discovery
      Note of Qi and Cuticchia.
AB  - The relative quantities of bases in DNA were determined chemically many years
      before sequencing technologies permitted direct counting of bases. Apparently
      unaware of the rich literature on the topic, bioinformaticists are today
      rediscovering the 'wheels' of Chargaff, Wyatt and other biochemists. It follows
      from Chargaff's second parity rule (%A = %T, %G = %C for single stranded DNA)
      that the symmetries observed for the two pairs of complementary mononucleotide
      bases, should also apply to the eight pairs of complementary dinucleotide bases,
      the thirty-two pairs of complementary trinucleotide bases, etc. This was made
      explicit by Prabhu in 1993 in a study of complete genomes and long genome
      segments from a wide range of taxa, and was rediscovered by Qi and Cuticchia in
      2001 in a study of complete genomes. It follows from Chargaff's GC-rule (%GC
      tends to be uniform and species specific) that, within a species,
      oligonucleotides of the same GC% will be at approximately equal quantities in
      single stranded DNA. Thus, for example, while quantities of CAT and ATG (reverse
      complements) will be closely correlated because of both of the above Chargaff
      rules, CAT and GTA (forward complements) will show some correlation only because
      of the latter rule. The need for complete genomic sequences in bioinformatic
      analyses may have been somewhat overplayed.

PMID- 11836241
TI  - Bax and Bak independently promote cytochrome C release from mitochondria.
AB  - Pro-apoptotic Bax and Bak have been implicated in the regulation of p53-dependent
      apoptosis. We assessed the ability of primary baby mouse kidney (BMK) epithelial
      cells from bax(-/-), bak(-/-), and bax(-/-) bak(-/-) mice to be transformed by
      E1A alone or in conjunction with dominant-negative p53 (p53DD). Although E1A
      alone transformed BMK cells from p53-deficient mice, E1A alone did not transform
      BMK cells from bax(-/-), bak(-/-), or bax(-/-) bak(-/-) mice. Thus, the loss of
      both Bax and Bak was not sufficient to relieve p53-dependent suppression of
      transformation in epithelial cells. To test the requirement for Bax and Bak in
      other death signaling pathways, stable E1A plus p53DD-transformed BMK cell lines
      were derived from the bax(-/-), bak(-/-), and bax(-/-) bak(-/-) mice and
      characterized for their response to tumor necrosis factor-alpha (TNF-alpha)
      mediated apoptosis. The loss of both Bax and Bak severely impaired TNF-alpha
      mediated apoptosis, but the presence of either Bax or Bak alone was sufficient
      for cell death. Cytochrome c was released from mitochondria, and caspase-9 was
      activated in Bax- or Bak-deficient cells in response to TNF-alpha but not in
      cells deficient in both. Thus, either Bax or Bak is required for death signaling
      through mitochondria in response to TNF-alpha, but both are dispensable for p53
      dependent transformation inhibition.

PMID- 11836242
TI  - Heliothis virescens and Manduca sexta lipid rafts are involved in Cry1A toxin
      binding to the midgut epithelium and subsequent pore formation.
AB  - Lipid rafts are characterized by their insolubility in nonionic detergents such
      as Triton X-100 at 4 degrees C. They have been studied in mammals, where they
      play critical roles in protein sorting and signal transduction. To understand the
      potential role of lipid rafts in lepidopteran insects, we isolated and analyzed
      the protein and lipid components of these lipid raft microdomains from the midgut
      epithelial membrane of Heliothis virescens and Manduca sexta. Like their
      mammalian counterparts, H. virescens and M. sexta lipid rafts are enriched in
      cholesterol, sphingolipids, and glycosylphosphatidylinositol-anchored proteins.
      In H. virescens and M. sexta, pretreatment of membranes with the cholesterol
      depleting reagent saponin and methyl-beta-cyclodextrin differentially disrupted
      the formation of lipid rafts, indicating an important role for cholesterol in
      lepidopteran lipid rafts structure. We showed that several putative Bacillus
      thuringiensis Cry1A receptors, including the 120- and 170-kDa aminopeptidases
      from H. virescens and the 120-kDa aminopeptidase from M. sexta, were
      preferentially partitioned into lipid rafts. Additionally, the leucine
      aminopeptidase activity was enriched approximately 2-3-fold in these rafts
      compared with brush border membrane vesicles. We also demonstrated that Cry1A
      toxins were associated with lipid rafts, and that lipid raft integrity was
      essential for in vitro Cry1Ab pore forming activity. Our study strongly suggests
      that these microdomains might be involved in Cry1A toxin aggregation and pore
      formation.

PMID- 11836243
TI  - Differential use of myristoyl groups on neuronal calcium sensor proteins as a
      determinant of spatio-temporal aspects of Ca2+ signal transduction.
AB  - The localizations of three members of the neuronal calcium sensor (NCS) family
      were studied in HeLa cells. Using hippocalcin-EYFP and NCS-1-ECFP, it was found
      that their localization differed dramatically in resting cells. NCS-1 had a
      distinct predominantly perinuclear localization (similar to trans-Golgi markers),
      whereas hippocalcin was present diffusely throughout the cell. Upon the elevation
      of intracellular Ca(2+), hippocalcin rapidly translocated to the same perinuclear
      compartment as NCS-1. Another member of the family, neurocalcin delta, also
      translocated to this region after a rise in Ca(2+) concentration.
      Permeabilization of transfected cells using digitonin caused loss of hippocalcin
      and neurocalcin delta in the absence of calcium, but in the presence of 10 microm
      Ca(2+), both proteins translocated to and were retained in the perinuclear
      region. NCS-1 localization was unchanged in permeabilized cells regardless of
      calcium concentration. The localization of NCS-1 was unaffected by mutations in
      all functional EF hands, indicating that its localization was independent of
      Ca(2+). A minimal myristoylation motif (hippocalcin-(1-14)) fused to EGFP
      resulted in similar perinuclear targeting, showing that localization of these
      proteins is because of the exposure of the myristoyl group. This was confirmed by
      mutation of the myristoyl motif of NCS-1 and hippocalcin that resulted in both
      proteins remaining cytosolic, even at elevated Ca(2+) concentration. Dual imaging
      of hippocalcin-EYFP and cytosolic Ca(2+) concentration in Fura Red-loaded cells
      demonstrated the kinetics of the Ca(2+)/myristoyl switch in living cells and
      showed that hippocalcin rapidly translocated with a half-time of approximately 12
      s after a short lag period when Ca(2+) was elevated. These results demonstrate
      that closely related Ca(2+) sensor proteins use their myristoyl groups in
      distinct ways in vivo in a manner that will determine the time course of Ca(2+)
      signal transduction.

PMID- 11836244
TI  - MRK, a mixed lineage kinase-related molecule that plays a role in gamma-radiation
      induced cell cycle arrest.
AB  - Mitogen-activated protein (MAP) kinase pathways are three-kinase modules that
      mediate diverse cellular processes and have been highly conserved among
      eukaryotes. By using a functional complementation screen in yeast, we have
      identified a human MAP kinase kinase kinase (MAPKKK) that shares homology with
      members of the mixed lineage kinase (MLK) family and therefore was called MRK
      (MLK-related kinase). We report the structure of the MRK gene, from which are
      generated two splice forms of MRK, MRK-alpha and MRK-beta, encoding for proteins
      of 800 and 456 amino acids, respectively. By using a combination of solid phase
      protein kinase assays, transient transfections in cells, and analysis of
      endogenous proteins in stably transfected Madin-Darby canine kidney cells, we
      found that MRK-beta preferentially activates ERK6/p38gamma via MKK3/MKK6 and JNK
      through MKK4/MKK7. We also show that expression of wild type MRK increases the
      cell population in the G(2)/M phase of the cell cycle, whereas dominant negative
      MRK attenuates the G(2) arrest caused by gamma-radiation. In addition, exposure
      of cells to gamma-radiation induces MRK activity. These data suggest that MRK may
      mediate gamma-radiation signaling leading to cell cycle arrest and that MRK
      activity is necessary for the cell cycle checkpoint regulation in cells.

PMID- 11836245
TI  - Functional cloning, heterologous expression, and purification of two different N
      deoxyribosyltransferases from Lactobacillus helveticus.
AB  - Lactobacillus helveticus contains two types of N-deoxyribosyltransferases: DRTase
      I catalyzes the transfer of 2'-deoxyribose between purine bases exclusively
      whereas DRTase II is able to transfer the 2'-deoxyribose between two pyrimidine
      or between pyrimidine and purine bases. An Escherichia coli strain, auxotrophic
      for guanine and unable to use deoxyguanosine as source of guanine, was
      constructed to clone the corresponding genes. By screening a genomic bank for the
      production of guanine, the L. helveticus ptd and ntd genes coding for DRTase I
      and II, respectively, were isolated. Although the two genes have no sequence
      similarity, the two deduced polypeptides display 25.6% identity, with most of the
      residues involved in substrate binding and the active site nucleophile Glu-98
      being conserved. Overexpression and purification of the two proteins shows that
      DRTase I is specific for purines with a preference for deoxyinosine (dI) >
      deoxyadenosine > deoxyguanosine as donor substrates whereas DRTase II has a
      strong preference for pyrimidines as donor substrates and purines as base
      acceptors. Purine analogues were substrates as acceptor bases for both enzymes.
      Comparison of DRTase I and DRTase II activities with dI as donor or hypoxanthine
      as acceptor and colocalization of the ptd and add genes suggest a specific role
      for DRTase I in the metabolism of dI.

PMID- 11836247
TI  - Sustained ER Ca2+ depletion suppresses protein synthesis and induces activation
      enhanced cell death in mast cells.
AB  - Depletion of Ca(2+) from the endoplasmic reticulum (ER) induces large increases
      in cytoplasmic Ca(2+), mitochondrial Ca(2+) loading, protein synthesis
      inhibition, and cell death. To clarify the connections among these events, we
      have evaluated the effect of Ca(2+) mobilizing agents thapsigargin (Tg),
      econazole (Ec), and the growth factor Steel Factor (SLF) on bone marrow-derived
      mast cells (BMMCs). BMMC Ca(2+) stores were found to consist of a Tg-sensitive ER
      compartment, the Tg-insensitive SIC store, and mitochondrial stores. Low levels
      of Ec interfered with Tg-stimulated mitochondrial loading while promoting
      progressive leakage of Ca(2+) from the ER. Low levels of Ec completely reversed
      Tg toxicity while higher levels blocked store-operated influx and induced cell
      death in a SLF-enhanced manner. Both Ec and Tg inhibited protein synthesis,
      however, only SLF plus Tg or very high levels of Ec were able to significantly
      stimulate EIF-2alpha phosphorylation. Cycloheximide only partially protected
      BMMCs from Tg toxicity yet strongly synergized with Ec to induce cell death.
      These results therefore indicate that although both Tg and Ec deplete ER Ca(2+)
      levels, Ec-induced cell death results from sustained protein synthesis inhibition
      while Tg toxicity results primarily from mitochondrial Ca(2+) overload and
      secondarily from ER stress associated with Ca(2+) depletion.

PMID- 11836246
TI  - Distinct retinoid metabolic functions for alcohol dehydrogenase genes Adh1 and
      Adh4 in protection against vitamin A toxicity or deficiency revealed in double
      null mutant mice.
AB  - The ability of class I alcohol dehydrogenase (ADH1) and class IV alcohol
      dehydrogenase (ADH4) to metabolize retinol to retinoic acid is supported by
      genetic studies in mice carrying Adh1 or Adh4 gene disruptions. To differentiate
      the physiological roles of ADH1 and ADH4 in retinoid metabolism we report here
      the generation of an Adh1/4 double null mutant mouse and its comparison to single
      null mutants. We demonstrate that loss of both ADH1 and ADH4 does not have
      additive effects, either for production of retinoic acid needed for development
      or for retinol turnover to minimize toxicity. During gestational vitamin A
      deficiency Adh4 and Adh1/4 mutants exhibit completely penetrant postnatal
      lethality by day 15 and day 24, respectively, while 60% of Adh1 mutants survive
      to adulthood similar to wild-type. Following administration of a 50-mg/kg dose of
      retinol to examine retinol turnover, Adh1 and Adh1/4 mutants exhibit similar 10
      fold decreases in retinoic acid production, whereas Adh4 mutants have only a
      slight decrease. LD(50) studies indicate a large increase in acute retinol
      toxicity for Adh1 mutants, a small increase for Adh4 mutants, and an intermediate
      increase for Adh1/4 mutants. Chronic retinol supplementation during gestation
      resulted in 65% postnatal lethality in Adh1 mutants, whereas only approximately
      5% for Adh1/4 and Adh4 mutants. These studies indicate that ADH1 provides
      considerable protection against vitamin A toxicity, whereas ADH4 promotes
      survival during vitamin A deficiency, thus demonstrating largely non-overlapping
      functions for these enzymes in retinoid metabolism.

PMID- 11836248
TI  - Identification and characterization of a novel endoplasmic reticulum (ER) DnaJ
      homologue, which stimulates ATPase activity of BiP in vitro and is induced by ER
      stress.
AB  - The activity of Hsp70 proteins is regulated by accessory proteins, which include
      members of the DnaJ-like protein family. Characterized by the presence of a
      highly conserved 70-amino acid J domain, DnaJ homologues activate the ATPase
      activity of Hsp70 proteins and stabilize their interaction with unfolded
      substrates. DnaJ homologues have been identified in most organelles where they
      are involved in nearly all aspects of protein synthesis and folding. Within the
      endoplasmic reticulum (ER), DnaJ homologues have also been shown to assist in the
      translocation, secretion, retro-translocation, and ER-associated degradation
      (ERAD) of secretory pathway proteins. By using bioinformatic methods, we
      identified a novel mammalian DnaJ homologue, ERdj4. It is the first ER-localized
      type II DnaJ homologue to be reported. The signal sequence of ERdj4 remains
      uncleaved and serves as a membrane anchor, orienting its J domain into the ER
      lumen. ERdj4 co-localized with GRP94 in the ER and associated with BiP in vivo
      when they were co-expressed in COS-1 cells. In vitro experiments demonstrated
      that the J domain of ERdj4 stimulated the ATPase activity of BiP in a
      concentration-dependent manner. However, mutation of the hallmark tripeptide HPD
      (His --> Gln) in the J domain totally abolished this activation. ERdj4 mRNA
      expression was detected in all human tissues examined but showed the highest
      level of the expression in the liver, kidney, and placenta. We found that ERdj4
      was highly induced at both the mRNA and protein level in response to ER stress,
      indicating that this protein might be involved in either protein folding or ER
      associated degradation.

PMID- 11836249
TI  - Identification and characterization of three members of the human
      metallocarboxypeptidase gene family.
AB  - Amino acid homology searches of the human genome revealed three members of the
      metallocarboxypeptidase (metallo-CP) family that had not been described in the
      literature in addition to the 14 known genes. One of these three, named CPA5, is
      present in a gene cluster with CPA1, CPA2, and CPA4 on chromosome 7. The cDNA
      encoding a mouse homolog of human CPA5 was isolated from a testis library and
      sequenced. The deduced amino acid sequence of human CPA5 has highest amino acid
      sequence identity (60%) to CPA1. Modeling analysis shows the overall structure to
      be very similar to that of other members of the A/B subfamily of
      metallocarboxypeptidases. The active site of CPA5 is predicted to cleave
      substrates with C-terminal hydrophobic residues, as do CPA1, -2, and -3. Using
      Northern blot analysis, CPA5 mRNA is detected in testis but not in kidney, liver,
      brain, or lung. In situ hybridization analysis shows that CPA5 is localized to
      testis germ cells. Mouse pro-CPA5 protein expressed in Sf9 cells using the
      baculovirus system was retained in the particulate fraction of the cells and was
      not secreted into the media. Pro-CPA5 was not enzymatically active toward
      standard CPA substrates, but after incubation with prohormone convertase 4 the
      resulting protein was able to cleave furylacryloyl-Gly-Leu, with 3-4-fold greater
      activity at pH 7.4 than at 5.6. Two additional members of the human CP gene
      family were also studied. Modeling analysis indicates that both contain the
      necessary amino acids required for enzymatic activity. The CP on chromosome 8 is
      predicted to have a CPA-like specificity for C-terminal hydrophobic residues and
      was named CPA6. The CP on chromosome 2 is predicted to cleave substrates with C
      terminal acidic residues and was named CPO.

PMID- 11836250
TI  - Structure of two iron-binding proteins from Bacillus anthracis.
AB  - Bacillus anthracis is currently under intense investigation due to its primary
      importance as a human pathogen. Particularly important is the development of
      novel anti-anthrax vaccines, devoid of the current side effects. A novel class of
      immunogenic bacterial proteins consists of dodecamers homologous to the DNA
      binding protein of Escherichia coli (Dps). Two Dps homologous genes are present
      in the B. anthracis genome. The crystal structures of these two proteins (Dlp-1
      and Dlp-2) have been determined and are presented here. They are sphere-like
      proteins with an internal cavity. We also show that they act as ferritins and are
      thus involved in iron uptake and regulation, a fundamental function during
      bacterial growth.

PMID- 11836251
TI  - Murine Sall1 represses transcription by recruiting a histone deacetylase complex.
AB  - The multi-zinc finger proteins of the Sal family regulate organogenesis. Genetic
      evidence from Drosophila has shown that spalt (sal) can alter gene expression in
      a cell autonomous fashion, but Sal proteins have never been directly analyzed for
      their ability to activate or repress transcription. In this report, we show that
      a member of the Sal family, mouse Sall1, is a potent transcriptional repressor.
      When fused to a heterologous DNA-binding domain, Sall1 represses transcription of
      a luciferase reporter by over 100-fold. Expression of the N terminus alone is
      sufficient for dose-responsive repression that, as shown by deletion analysis,
      requires the extreme N-terminal amino acids of the protein. The N terminus of
      Sall1 can repress at both short and long range relative to the promoter, and
      treatment with the histone deacetylase (HDAC) inhibitor, trichostatin A,
      alleviates repression by 3-fold. The same regions of the protein that are
      required for repression physically interact with components of chromatin
      remodeling complexes, HDAC1, HDAC2, RbAp46/48, MTA-1, and MTA-2. Finally, we
      demonstrate that Sall1 is localized to discrete nuclear foci and this
      localization depends on the N-terminal repression domain. Together, these results
      suggest that the N terminus of mouse Sall1 can recruit HDAC complexes to mediate
      transcriptional repression.

PMID- 11836252
TI  - Genetic rescue of Leishmania deficiency in porphyrin biosynthesis creates mutants
      suitable for analysis of cellular events in uroporphyria and for photodynamic
      therapy.
AB  - Leishmania was found deficient in at least five and most likely seven of the
      eight enzymes in the heme biosynthesis pathway, accounting for their growth
      requirement for heme compounds. The xenotransfection of this trypanosomatid
      protozoan led to their expression of the mammalian genes encoding delta
      aminolevulinate (ALA) dehydratase and porphobilinogen deaminase, the second and
      the third enzymes of the pathway, respectively. These transfectants still require
      hemin or protoporphyrin IX for growth but produce porphyrin when ALA was supplied
      exogenously. Leishmania is thus deficient in all first three enzymes of the
      pathway. Uroporphyrin I was produced as the sole intermediate by these
      transfectants, further indicating that they are also deficient in at least two
      porphyrinogen-metabolizing enzymes downstream of porphobilinogen deaminase, i.e.
      uroporphyrinogen III co-synthase and uroporphyrinogen decarboxylase. Pulsing the
      transfectants with ALA induced their transition from aporphyria to uroporphyria.
      Uroporphyrin I emerged in these cells initially as diffused throughout the
      cytosol, rendering them sensitive to UV irradiation. The porphyrin was
      subsequently sequestered in cytoplasmic vacuoles followed by its release and
      accumulation in the extracellular milieu, concomitant with a reduced
      photosensitivity of the cells. These events may represent cellular mechanisms for
      disposing soluble toxic waste from the cytosol. Monocytic tumor cells were
      rendered photosensitive by infection with uroporphyric Leishmania, suggestive of
      their potential application for photodynamic therapy.

PMID- 11836253
TI  - The mushroom Marasmius oreades lectin is a blood group type B agglutinin that
      recognizes the Galalpha 1,3Gal and Galalpha 1,3Galbeta 1,4GlcNAc porcine
      xenotransplantation epitopes with high affinity.
AB  - A blood group B-specific lectin from the mushroom Marasmius oreades (MOA) was
      investigated with respect to its molecular structure and carbohydrate binding
      properties. SDS-PAGE mass spectrometric analysis showed it to consist of an
      intact (H; 33 kDa) and truncated (L; 23 kDa) subunit in addition to a small
      polypeptide (P; 10 kDa). Isolation in the presence of EDTA produced only the H
      subunits, indicating that the latter two are formed by metalloprotease cleavage
      of the intact H subunit. Tryptic digestion of the H, L, and P polypeptide chains
      followed by mass spectral analysis supports this view. The lectin strongly
      precipitated blood group type B substance, was nonreactive with type A substance,
      and reacted weakly with type H substance. Carbohydrate binding studies reveal a
      high affinity for Galalpha1,3Gal (but not for the isomeric alpha1,2-, alpha1,4-,
      and alpha1,6-disaccharides); Galalpha1,3Galbeta1,4GlcNAc; and the type B branched
      trisaccharide. MOA also reacts strongly with murine laminin from the Engelbreth
      Holm-Swarm sarcoma and bovine thyroglobulin, both of which contain multiple
      Galalpha1,3Galbeta1,4GlcNAc end groups. This linear B trisaccharide is a
      component of porcine tissues and organs, preventing their transplantation into
      humans. MOA also shares carbohydrate recognition of this trisaccharide with toxin
      A elaborated by Clostridium difficile.

PMID- 11836254
TI  - Cloning, expression, and characterization of the Galalpha 1,3Gal high affinity
      lectin from the mushroom Marasmius oreades.
AB  - The purification and unique carbohydrate binding properties, including blood
      group B-specific agglutination and preferential binding to Galalpha1,3Gal
      containing sugar epitopes, of the Marasmius oreades agglutinin (MOA) are reported
      in an accompanying paper (Winter, H. C., Mostafapour, K., and Goldstein, I. J.
      (2002) J. Biol. Chem. 277, 14996-15001). Here we describe the cloning,
      characterization, and expression of MOA. MOA was digested with trypsin and
      endoproteinase Asp-N, and the peptide fragments were purified by high performance
      liquid chromatography. Amino acid sequence data were obtained for eight peptides.
      Using oligonucleotides deduced from the peptide sequences for a reverse
      transcriptase-PCR, a 41-base pair cDNA was obtained. The 41-base pair fragment
      allowed the generation a full-length cDNA using 5' and 3' rapid amplification of
      cDNA ends. MOA cDNA encodes a protein of 293 amino acids that contains a ricin
      domain. These carbohydrate binding domains were first described in subunits of
      bacterial toxins and are also commonly found in polysaccharide-degrading enzymes.
      Whereas these proteins are known to display a variety of sugar binding
      specificities, none to date are known to share MOA's high affinity for
      Galalpha1,3Gal and Galalpha1,3Galbeta1,4GlcNAc. Recombinantly expressed and
      purified MOA retains the specificity and affinity observed with the native
      protein. This study provides the basis for analyzing the underlying cause for the
      unusual binding specificity of MOA.

PMID- 11836255
TI  - Molecular mechanism of the induction of metalloproteinases 1 and 3 in human
      fibroblasts by basic calcium phosphate crystals. Role of calcium-dependent
      protein kinase C alpha.
AB  - Synovial fluid basic calcium phosphate (BCP) crystals are common in
      osteoarthritis and are often associated with destructive arthropathies involving
      cartilage degeneration. These crystals are mitogenic and induce oncogene
      expression and matrix metalloproteinase (MMP) synthesis and secretion in human
      fibroblasts. To date, BCP crystal-elicited signal transduction pathways have not
      been completely studied. Because protein kinase C (PKC) is known to play an
      important role in signal transduction, we investigated the participation of this
      pathway in the BCP crystal induction of MMP-1 and MMP-3 mRNA and protein
      expressions in human fibroblasts. Using reverse transcription/polymerase chain
      reaction (RT-PCR) and Northern and Western blotting techniques, we show here that
      BCP crystal stimulation of MMP-1 and MMP-3 mRNA and protein expressions in human
      fibroblasts is dependent upon the calcium-dependent PKC signal transduction
      pathway and that the PKC alpha isozyme is specifically involved in the pathway.
      We have previously shown that BCP crystal induction of MMP-1 and MMP-3 is also
      dependent on the p44/42 mitogen-activated protein kinase (p44/42 MAPK) signal
      transduction pathway. We now show that these two pathways operate independently
      and seem to complement each other. This leads to our hypothesis that the two
      pathways initially function independently, ultimately leading to an increase in
      mitogenesis and MMP synthesis, and may converge downstream of PKC and p44/42 MAPK
      to mediate BCP crystal-induced cellular responses.

PMID- 11836256
TI  - Novel pathways associated with bypassing cellular senescence in human prostate
      epithelial cells.
AB  - Cellular senescence forms a barrier that inhibits the acquisition of an immortal
      phenotype, a critical feature in tumorigenesis. The inactivation of multiple
      pathways that positively regulate senescence are required for immortalization. To
      identify these pathways in an unbiased manner, we performed DNA microarray
      analyses to assess the expression of 20,000 genes in human prostate epithelial
      cells (HPECs) passaged to senescence. These gene expression patterns were then
      compared with those of HPECs immortalized with the human Papillomavirus 16 E7
      oncoprotein. Senescent cells display gene expression patterns that reflect their
      nonproliferative, differentiated phenotype and express secretory proteases and
      extracellular matrix components. A comparison of genes transcriptionally up
      regulated in senescence to those in which expression is significantly down
      regulated in immortalized HPECs identified three genes: the chemokine BRAK, DOC1,
      and a member of the insulin-like growth factor axis, IGFBP-3. Expression of these
      genes is found to be uniformly lost in human prostate cancer cell lines and
      xenografts, and previously, their inactivation was documented in tumor samples.
      Thus, these genes may function in novel pathways that regulate senescence and are
      inactivated during immortalization. These changes may be critical not only in
      allowing cells to bypass senescence in vitro but in the progression of prostate
      cancer in vivo.

PMID- 11836257
TI  - Novel signal transduction pathway utilized by extracellular HSP70: role of toll
      like receptor (TLR) 2 and TLR4.
AB  - Recent studies have initiated a paradigm shift in the understanding of the
      function of heat shock proteins (HSP). It is now clear that HSP can and do exit
      mammalian cells, interact with cells of the immune system, and exert
      immunoregulatory effects. We recently demonstrated that exogenously added HSP70
      possesses potent cytokine activity, with the ability to bind with high affinity
      to the plasma membrane, elicit a rapid intracellular Ca(2+) flux, activate NF
      kappaB, and up-regulate the expression of pro-inflammatory cytokines in human
      monocytes. Here for the first time, we report that HSP70-induced proinflammatory
      cytokine production is mediated via the MyD88/IRAK/NF-kappaB signal transduction
      pathway and that HSP70 utilizes both TLR2 (receptor for Gram-positive bacteria)
      and TLR4 (receptor for Gram-negative bacteria) to transduce its proinflammatory
      signal in a CD14-dependent fashion. These studies now pave the way for the
      development of highly effective pharmacological or molecular tools that will
      either up-regulate or suppress HSP70-induced functions in conditions where HSP70
      effects are desirable (cancer) or disorders where HSP70 effects are undesirable
      (arthritis and arteriosclerosis).

PMID- 11836258
TI  - Passive acquisition of ligand by the MopII molbindin from Clostridium
      pasteurianum: structures of apo and oxyanion-bound forms.
AB  - MopII from Clostridium pasteurianum is a molbindin family member. These proteins
      may serve as intracellular storage facilities for molybdate, which they bind with
      high specificity. High resolution structures of MopII in a number of states,
      including the first structure of an apo-molbindin, together with calorimetric
      data, allow us to describe ligand binding and provide support for the proposed
      storage function of the protein. MopII assembles as a trimer of dimers and binds
      eight oxyanions at two types of binding sites located at intersubunit interfaces.
      Two type 1 sites are on the molecular 3-fold axis and three pairs of type 2 sites
      occur on the molecular 2-fold axes. The hexamer is largely unaffected by the
      binding of ligand. Molybdate is admitted to the otherwise inaccessible type 2
      binding sites by the movement of the N-terminal residues of each protein chain.
      This contrasts with the structurally related molybdate-dependent transcriptional
      regulator ModE, which undergoes extensive conformational rearrangements on ligand
      binding. Despite similarities between the binding sites of ModE and the type 2
      sites of MopII the molbindin has a significantly reduced ligand affinity, due, in
      part, to the high density of negative charges at the center of the hexamer. In
      the absence of ligand this effects the movement of an important lysine side
      chain, thereby partially inactivating the binding sites. The differences are
      consistent with a biological role in molybdate storage/buffering.

PMID- 11836259
TI  - Reactive brominating species produced by myeloperoxidase target the vinyl ether
      bond of plasmalogens: disparate utilization of sodium halides in the production
      of alpha-halo fatty aldehydes.
AB  - Plasmalogens are a phospholipid molecular subclass that are enriched in the
      plasma membrane of many mammalian cells. The present study demonstrates that
      reactive brominating species produced by myeloperoxidase, as well as activated
      neutrophils, attack the vinyl ether bond of plasmalogens. Reactive brominating
      species produced by myeloperoxidase target the vinyl ether bond of plasmalogens,
      resulting in the production of a neutral lipid and lysophosphatidylcholine. Gas
      chromatography-mass spectrometry and proton NMR analyses of this neutral lipid
      demonstrated that it was 2-bromohexadecanal (2-BrHDA). In comparison to
      myeloperoxidase-generated reactive chlorinating species, reactive brominating
      species attacked the plasmalogen vinyl ether bond at neutral pH. In the presence
      of a 20-fold molar excess of NaCl compared with NaBr, myeloperoxidase-derived
      reactive halogenating species favored the production of 2-BrHDA over that of 2
      chlorohexadecanal. Additionally, 2-BrHDA was preferentially produced from
      plasmalogen treated with hypochlorous acid in the presence of NaBr. The potential
      physiological significance of this pathway was suggested by the demonstration
      that both 2-BrHDA and 2-bromooctadecanal were produced by PMA-stimulated
      neutrophils. Taken together, the present studies demonstrate the targeting of the
      vinyl ether bond of plasmalogens by the reactive brominating species produced by
      myeloperoxidase and by activated neutrophils, resulting in the production of
      novel brominated fatty aldehydes.

PMID- 11836260
TI  - Liprin beta 1, a member of the family of LAR transmembrane tyrosine phosphatase
      interacting proteins, is a new target for the metastasis-associated protein
      S100A4 (Mts1).
AB  - Metastasis-associated protein S100A4 (Mts1) induces invasiveness of primary
      tumors and promotes metastasis. S100A4 belongs to the family of small calcium
      binding S100 proteins that are involved in different cellular processes as
      transducers of calcium signal. S100A4 modulates properties of tumor cells via
      interaction with its intracellular targets, heavy chain of non-muscle myosin and
      p53. Here we report identification of a new molecular target of the S100A4
      protein, liprin beta1. Liprin beta1 belongs to the family of leukocyte common
      antigen-related (LAR) transmembrane tyrosine phosphatase-interacting proteins
      that may regulate LAR protein properties via interaction with another member of
      the family, liprin alpha1. We showed by the immunoprecipitation analysis that
      S100A4 interacts specifically with liprin beta1 in vivo. Immunofluorescence
      staining demonstrated the co-localization of S100A4 and liprin beta1 in the
      cytoplasm and particularly at the protrusion sites of the plasma membrane. We
      mapped the S100A4 binding site at the C terminus of the liprin beta1 molecule
      between amino acid residues 938 and 1005. The S100A4-binding region contains two
      putative phosphorylation sites by protein kinase C and protein kinase CK2. S100A4
      liprin beta1 interaction resulted in the inhibition of liprin beta1
      phosphorylation by both kinases in vitro.

PMID- 11836262
TI  - Clinical review 141: lipids and atherosclerosis: lessons learned from randomized
      controlled trials of lipid lowering and other relevant studies.

PMID- 11836263
TI  - Dermopathy of Graves' disease (pretibial myxedema): long-term outcome.
AB  - Little is known about the long-term outcome of patients with thyroid dermopathy,
      an extrathyroidal manifestation of Graves' disease. Also, it is not known to what
      degree treatment promotes remission of the lesions. The present report supplies
      information on the natural course of mild, untreated and severe, treated thyroid
      dermopathy. In this study, we report on the outcomes of 178 patients seen at our
      institution between January 1969 and November 1995 with thyroid dermopathy who
      were followed up for an average of 7.9 yr. Nonpitting edema was the most
      prevalent form of dermopathy (43.3%), and the pretibial area was the region most
      commonly involved (99.4%). The majority of patients with dermopathy had
      ophthalmopathy (97.0%). Topical corticosteroids were the most commonly used
      treatment (53.9%). Patients with milder forms of dermopathy (40.4%) did not
      receive any therapy for dermopathy. Twenty-six percent of the patients
      experienced complete remission, 24.2% had moderate improvement (partial
      remission), and 50.0% had no or minimal improvement of their dermopathy at last
      follow-up. Patients who did not receive therapy experienced a significantly (P =
      0.03) higher rate of complete remission (34.7%) than those who received local
      therapy (18.7%), although the combined complete and partial remission rates were
      not significantly different for the treated and untreated groups (P = 0.3).
      However, the treated and untreated groups were not comparable because our
      practice is to use therapy for more extensive and severe cases. All five cases of
      elephantiasis were in the treatment group and were less likely to have remission
      because of the severity of their skin condition. Patients receiving treatment
      were more likely to have dermatologic consultation and histologic diagnosis (P <
      0.001). The beneficial effect of topical corticosteroid therapy on long-term
      remission rates remains to be determined.

PMID- 11836265
TI  - Aldosterone--an independent risk factor in cardiovascular disease.

PMID- 11836267
TI  - Aggressive pituitary tumors in MEN1: do they refute the two-hit model of
      tumorigenesis?

PMID- 11836266
TI  - Spironolactone abolishes the relationship between aldosterone and plasminogen
      activator inhibitor-1 in humans.
AB  - Recent studies have defined a link between the renin-angiotensin-aldosterone
      system and fibrinolysis. The present study tests the hypothesis that endogenous
      aldosterone regulates plasminogen activator inhibitor-1 (PAI-1) production in
      humans. Hemodynamic parameters, PAI-1 and tissue-type plasminogen activator (t
      PA) antigen, potassium, PRA, angiotensin II, and aldosterone were measured in
      nine male hypertensive subjects after a 3-wk washout, after 2 wk of
      hydrochlorothiazide (HCTZ; 25 mg plus 20 mmol KCl/d), and after 2 wk of
      spironolactone (100 mg/d plus KCl placebo). Spironolactone (P = 0.04), but not
      HCTZ (P = 0.57 vs. baseline; P = 0.1 vs. spironolactone), significantly lowered
      systolic blood pressure. Angiotensin II increased from baseline during both HCTZ
      (P = 0.02) and spironolactone (P = 0.02 vs. baseline; P = 0.19 vs. HCTZ)
      treatments. Although both HCTZ (P = 0.004) and spironolactone (P < 0.001 vs.
      baseline) increased aldosterone, the effect was greater with spironolactone (P <
      0.001 vs. HCTZ). HCTZ increased PAI-1 antigen (P = 0.02), but did not alter t-PA
      antigen. In contrast, there was no effect of spironolactone on PAI-1 antigen (P =
      0.28), whereas t-PA antigen was increased (P = 0.01). There was a significant
      correlation between PAI-1 antigen and serum aldosterone during both baseline and
      HCTZ study days (r(2) = 0.57; P = 0.0003); however, treatment with spironolactone
      abolished this correlation (r(2) = 0.13; P = 0.33). This study provides evidence
      that endogenous aldosterone influences PAI-1 production in humans.

PMID- 11836268
TI  - Pituitary disease in MEN type 1 (MEN1): data from the France-Belgium MEN1
      multicenter study.
AB  - To date, data on pituitary adenomas in MEN type 1 (MEN1) still have to be
      evaluated. We analyzed the data of a large series of 324 MEN1 patients from a
      French and Belgian multicenter study. Data on pituitary disease were compared
      with those from 110 non-MEN1 patients with pituitary adenomas, matched for age,
      year of diagnosis, and follow-up period. Genetic analysis of the MEN1 gene was
      performed in 197 of the MEN1 patients. In our MEN1 series, pituitary disease
      occurred in 136 of 324 (42%), less frequently than hyperparathyroidism (95%, P <
      0.001) and endocrine enteropancreatic tumors (54%, P < 0.01). Mean age of onset
      of pituitary tumors was 38.0+/-15.3 yr (range, 12-83 yr). Pituitary disease was
      associated with hyperparathyroidism in 90% of cases, with enteropancreatic tumors
      in 47%, with adrenal tumors in 16%, and with thoracic neuroendocrine tumors in
      4%. Pituitary disease was the initial lesion of MEN1 in 17% of all MEN1 patients.
      MEN1 pituitary adenomas were significantly more frequent in women than in men
      (50% vs. 31%, P < 0.001). Among the 136 pituitary adenomas, there were 85
      prolactinomas and 12 GH-secreting, 6 ACTH-secreting, 13 cosecreting, and 20
      nonsecreting tumors. Eighty-five percent of MEN1-related pituitary lesions were
      macroadenomas (vs. 42% in non-MEN1 patients, P < 0.001), including 32% of
      invasive cases. Among secreting adenomas, hormonal hypersecretion was normalized,
      after treatment, in only 42% (vs. 90% in non-MEN1 patients, P < 0.001), with a
      median follow-up of 11.4 yr. No correlation was found between the type of MEN1
      germ-line mutation and the presence or absence of pituitary adenoma. Our study,
      based on a large group of MEN1 patients, shows that pituitary adenomas occur in
      42% of the cases and are characterized by a larger size and a more aggressive
      presentation than without MEN1.

PMID- 11836269
TI  - The clinical laboratory evaluation of GH responsiveness.

PMID- 11836270
TI  - Poor reproducibility of IGF-I and IGF binding protein-3 generation test in
      children with short stature and normal coding region of the GH receptor gene.
AB  - The IGF-I generation test has been proposed to select patients with GH
      insensitivity. Studies have shown that children with idiopathic short stature and
      GH deficiency, who were expected to be sensitive to GH, presented absent IGF-I
      and IGF binding protein (IGFBP)-3 responses and/or discordant results at IGF-I
      and IGFBP-3 generation test for unknown reasons. To assess the reproducibility of
      the generation test, we studied a group of 12 prepubertal children with short
      stature and normal GH secretion in whom defects in coding region of GH receptor
      gene were ruled out. All patients underwent the test twice. Discordant responses
      between the first and second test were found in five and six patients for IGF-I
      and IGFBP-3, respectively. When the results of the generation tests were
      compared, one notices that IGF-I generation has more concordant positive results
      than IGFBP-3. In eight generation tests that showed discordant results between
      IGF-I and IGFBP-3, seven presented a positive IGF-I with a negative IGFBP-3
      response. Taking both tests into account, all children presented a normal IGF-I
      generation. Our findings showed that IGF-I and IGFBP-3 generation test was not
      reproducible in children that should have responded to GH stimulation. We suggest
      that, when IGF-I and IGFBP-3 levels fail to respond in the generation test,
      another test should be performed to confirm GH insensitivity.

PMID- 11836271
TI  - Diagnosis of GH deficiency in adults--how good do the criteria need to be?

PMID- 11836272
TI  - Which patients do not require a GH stimulation test for the diagnosis of adult GH
      deficiency?
AB  - Adult GH deficiency (GHD) is currently diagnosed in patients with either a
      history of childhood-onset GHD or acquired hypothalamic-pituitary disease by GH
      stimulation testing. However, GH stimulation tests are invasive, time consuming,
      and associated with side effects. Based on preliminary analyses of patients
      enrolled in the U.S. Hypopituitary Control and Complications Study (HypoCCS), we
      proposed the presence of adult GHD could be predicted with 95% accuracy by the
      presence of three or more pituitary hormone deficiencies (PHDs) or a serum IGF-I
      concentration less than 84 microg/liter (11 nmol/liter). To validate the
      diagnostic utility of these criteria, we studied results obtained in 817 adult
      patients (mean [SD] age: 46.4 [15.7] yr, body mass index: 30.1 [7.2] kg/m(2))
      enrolled in HypoCCS who had serum GH concentrations from stimulation tests (11
      different tests used, excluding clonidine) and serum IGF-I (competitive binding
      RIA) measured at the central laboratory (Esoterix Endocrinology, Calabasas Hills,
      CA). When patients were stratified into subgroups on the basis of the presence of
      zero, one, two, three, and four additional PHDs, median (25th, 75th percentile)
      peak GH levels (micrograms per liter) were 3.5 (0.85, 7.1), 0.73 (0.18, 4.2),
      0.29 (0.05, 1.4), 0.06 (0.025, 0.295), and 0.025 (0.025, 0.07), respectively. The
      mean log (peak GH) concentration was significantly different among the subgroups
      (P < 0.05). The proportion of patients in each group with severe GHD diagnosed by
      stimulation testing (peak GH < 2.5 microg/liter) was 41%, 67%, 83%, 96%, and 99%
      for patients with zero, one, two, three, and four PHDs, respectively. The
      positive predictive values (PPVs) for GHD of three PHDs, four PHDs, and serum IGF
      I less than 84 microg/liter were 96%, 99%, and 96%, respectively. The PPV of
      these three diagnostic criteria was also 95% or more after excluding the data
      originally used to identify these potential predictors. Taken together, the
      presence of either three or four additional PHDs or IGF-I less than 84
      microg/liter (55% of the patients met at least one of these criteria) reliably
      predicted GHD with a high PPV (95%), high specificity (89%), and moderate
      sensitivity (69%). We concluded that patients with an appropriate clinical
      history and either the presence of three or four additional PHDs or serum IGF-I
      less than 84 microg/liter (measured in the Esoterix assay) do not require GH
      stimulation testing for the diagnosis of adult GHD. In clinical practice, we
      suggest that other causes of low serum IGF-I should be excluded before applying
      these diagnostic criteria.

PMID- 11836273
TI  - Guarding our nation's thyroid health.

PMID- 11836274
TI  - Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to
      1994): National Health and Nutrition Examination Survey (NHANES III).
AB  - NHANES III measured serum TSH, total serum T(4), antithyroperoxidase (TPOAb), and
      antithyroglobulin (TgAb) antibodies from a sample of 17,353 people aged > or =12
      yr representing the geographic and ethnic distribution of the U.S. population.
      These data provide a reference for other studies of these analytes in the U.S.
      For the 16,533 people who did not report thyroid disease, goiter, or taking
      thyroid medications (disease-free population), we determined mean concentrations
      of TSH, T(4), TgAb, and TPOAb. A reference population of 13,344 people was
      selected from the disease-free population by excluding, in addition, those who
      were pregnant, taking androgens or estrogens, who had thyroid antibodies, or
      biochemical hypothyroidism or hyperthyroidism. The influence of demographics on
      TSH, T(4), and antibodies was examined. Hypothyroidism was found in 4.6% of the
      U.S. population (0.3% clinical and 4.3% subclinical) and hyperthyroidism in 1.3%
      (0.5% clinical and 0.7% subclinical). (Subclinical hypothyroidism is used in this
      paper to mean mild hypothyroidism, the term now preferred by the American Thyroid
      Association for the laboratory findings described.) For the disease-free
      population, mean serum TSH was 1.50 (95% confidence interval, 1.46-1.54)
      mIU/liter, was higher in females than males, and higher in white non-Hispanics
      (whites) [1.57 (1.52-1.62) mIU/liter] than black non-Hispanics (blacks) [1.18
      (1.14-1.21) mIU/liter] (P < 0.001) or Mexican Americans [1.43 (1.40-1.46)
      mIU/liter] (P < 0.001). TgAb were positive in 10.4 +/- 0.5% and TPOAb, in 11.3 +/
      0.4%; positive antibodies were more prevalent in women than men, increased with
      age, and TPOAb were less prevalent in blacks (4.5 +/- 0.3%) than in whites (12.3
      +/- 0.5%) (P < 0.001). TPOAb were significantly associated with hypo or
      hyperthyroidism, but TgAb were not. Using the reference population, geometric
      mean TSH was 1.40 +/- 0.02 mIU/liter and increased with age, and was
      significantly lower in blacks (1.18 +/- 0.02 mIU/liter) than whites (1.45 +/-
      0.02 mIU/liter) (P < 0.001) and Mexican Americans (1.37 +/- 0.02 mIU/liter) (P <
      0.001). Arithmetic mean total T(4) was 112.3 +/- 0.7 nmol/liter in the disease
      free population and was consistently higher among Mexican Americans in all
      populations. In the reference population, mean total T(4) in Mexican Americans
      was (116.3 +/- 0.7 nmol/liter), significantly higher than whites (110.0 +/- 0.8
      nmol/liter) or blacks (109.4 +/- 0.8 nmol/liter) (P < 0.0001). The difference
      persisted in all age groups. In summary, TSH and the prevalence of antithyroid
      antibodies are greater in females, increase with age, and are greater in whites
      and Mexican Americans than in blacks. TgAb alone in the absence of TPOAb is not
      significantly associated with thyroid disease. The lower prevalence of thyroid
      antibodies and lower TSH concentrations in blacks need more research to relate
      these findings to clinical status. A large proportion of the U.S. population
      unknowingly have laboratory evidence of thyroid disease, which supports the
      usefulness of screening for early detection.

PMID- 11836275
TI  - Long-term follow-up of functional hypothalamic amenorrhea and prognostic factors.
AB  - This study evaluated the prognosis of functional hypothalamic amenorrhea (FHA)
      and the predictive factors of recovery, through a long-term follow-up. Ninety
      three women affected by FHA underwent a follow-up for an average period of 8.1 yr
      (range 7-9 yr). At the end of the follow-up, 65 (70.7%) patients recovered.
      Statistical analysis showed that there was no association between recovery and
      anamnestic causes of FHA or with the echographic ovarian morphology but
      identified the predictive factors of recovery as the basal body mass index (BMI),
      the basal cortisol, and androstenedione plasma levels. A higher basal BMI and A,
      and lower cortisol values are positive prognostic factors for the recovery. Also
      the BMI, acquired during the follow-up, is important for FHA resolution: in fact,
      in recovered women the BMI increased or remained stable, whereas in nonrecovered
      women it decreased or remained stable. At the end of the follow-up, 52 (74.3%)
      patients treated with hormone replacement therapy and 8 (80%) with no therapy
      recovered, but only 5 (41.7%) with oral contraceptive pills recovered.

PMID- 11836277
TI  - Longitudinal follow-up of bone density and body composition in children with
      precocious or early puberty before, during and after cessation of GnRH agonist
      therapy.
AB  - We studied bone mineral density (BMD), bone metabolism, and body composition in
      47 children with central precocious puberty (n = 36) or early puberty (n = 11)
      before, during, and after cessation of GnRH agonist. Bone density and body
      composition were measured with dual energy x-ray absorptiometry and expressed as
      SD scores. Bone age and biochemical parameters of bone turnover were assessed.
      Measurements were performed at baseline, after 6 months, and on a yearly basis
      thereafter. Mean lumbar spine BMD SD scores for chronological age were
      significantly higher than zero at baseline and decreased during treatment. Lumbar
      spine bone mineral apparent density and total body BMD did not differ from normal
      at baseline and showed no significant changes during treatment. In contrast, BMD
      SD scores for bone age were significantly lower than zero at baseline and at
      cessation of therapy. Two years after therapy, bone mineral apparent density and
      BMD SD scores for bone age and chronological age did not differ from normal.
      Markers of bone turnover decreased during treatment, mainly in the first 6
      months. Patients had increased percentage of fat and lean body mass at baseline.
      After an initial increase of percentage body fat during treatment, percentage
      body fat decreased and normalized within 1 yr after cessation of treatment. Our
      longitudinal analysis suggests that peak bone mass or body composition will not
      be impaired in patients with precocious or early puberty after GnRH agonist
      therapy.

PMID- 11836279
TI  - GH administration changes myosin heavy chain isoforms in skeletal muscle but does
      not augment muscle strength or hypertrophy, either alone or combined with
      resistance exercise training in healthy elderly men.
AB  - GH administration, either alone or combined with resistance exercise training
      (RT), has attracted interest as a means of increasing muscle mass and strength in
      the elderly. In the present study, 31 healthy, elderly men [age, 74 +/- 1 yr
      (mean +/- SEM)] were assigned to either RT [3 sessions/wk, 3-5 sets of 8-12
      repetition maximum (RM)/session] + placebo (n = 8), RT + GH (n = 8), GH (n = 8),
      or placebo (n = 7) in a randomized, placebo-controlled, double-blinded (RT +
      placebo and RT + GH) or single-blinded (GH or placebo) design. Measurements of:
      1) isokinetic quadriceps muscle strength; 2) quadriceps muscle power; 3)
      quadriceps muscle fiber type, size, and myosin heavy chain (MHC) composition; 4)
      quadriceps cross-sectional area (CSA) [nuclear magnetic resonance imaging
      (NMRI)]; 5) body composition (dual-energy x-ray absorptiometry scanning); and 6)
      GH-related serum markers were performed at baseline and after 12 wk. The final GH
      dose was 1.77 +/- 0.18 IU x d(-1) (approximately 7.2 +/- 0.8 microg x kg(-1) x d(
      1)). GH alone had no effect on isokinetic quadriceps muscle strength, power, CSA,
      or fiber size. However, a substantial increase in MHC 2X isoform was observed
      with GH administration alone, and this may be regarded as a change into a more
      youthful MHC composition, possibly induced by the rejuvenating of systemic IGF-I
      levels. RT + placebo caused substantial increases in quadriceps isokinetic
      strength, power, and CSA; but these RT induced improvements were not further
      augmented by additional GH administration. In the RT + GH group, there was a
      significant decrease in MHC 1 and 2X isoforms, whereas MHC 2A increased. RT,
      therefore, seems to overrule the changes in MHC composition induced by GH
      administration alone. Changes in body composition confirmed previous reports of
      decreased fat mass, increased fat-free mass, and unchanged bone mineral content
      with GH administration. A high incidence of side effects was reported. Our
      results do not support a role for GH as a means of increasing muscle strength or
      mass, either alone or combined with RT, in healthy elderly men; although GH
      administration alone may induce changes in MHC composition.

PMID- 11836280
TI  - Effects of metformin on early pregnancy loss in the polycystic ovary syndrome.
AB  - Polycystic ovary syndrome is the most common form of female infertility in the
      United States. In addition to poor conception rates, pregnancy loss rates are
      high (30-50%) during the first trimester. We hypothesized that hyperinsulinemic
      insulin resistance contributes to early pregnancy loss in the syndrome, and that
      decreasing hyperinsulinemic insulin resistance with metformin during pregnancy
      would reduce the rate of early pregnancy loss. We conducted a retrospective study
      of all women with polycystic ovary syndrome who were seen in an academic
      endocrinology clinic within the past 4.5 yr and who became pregnant during that
      time. Sixty-five women received metformin during pregnancy (metformin group) and
      31women did not (control group). The early pregnancy loss rate in the metformin
      group was 8.8% (6 of 68 pregnancies), as compared with 41.9% (13 of 31
      pregnancies) in the control group (P < 0.001). In the subset of women in each
      group with a prior history of miscarriage, the early pregnancy loss rate was
      11.1% (4 of 36 pregnancies) in the metformin group, as compared with 58.3% (7 of
      12 pregnancies) in the control group (P = 0.002). Metformin administration during
      pregnancy reduces first-trimester pregnancy loss in women with the polycystic
      ovary syndrome.

PMID- 11836281
TI  - An effective hormonal male contraceptive using testosterone undecanoate with oral
      or injectable norethisterone preparations.
AB  - Suppression of spermatogenesis to azoospermia is the goal of hormonal male
      contraception based on T combined with gestagens. The combination of the long
      acting T, ester testosterone undecanoate (TU), with norethisterone (NET)
      enanthate (E) showed high efficacy. In the present study, we tested the validity
      of this approach by varying the NET dose and mode of application. The aim of the
      study was to achieve high rates of suppression of spermatogenesis as reflected by
      sperm counts, monitor gonadotropins as well as other hormones, and evaluate any
      possible side effects. In a phase II clinical trial, groups of normal volunteers
      received: 1000 mg TU im at wk 2, 6, 12, and 18 combined with 200 mg NETE im at wk
      0, 6, 12, and 18 (group I); 1000 mg TU im and 400 mg NETE im at wk 0, 6, 12, and
      18 (group II); and 1000 mg TU im at wk 0, 6, 12, and 18 with daily oral NET
      acetate (NETA) from wk 0 to 24 (group III). In all groups marked suppression of
      gonadotropins resulted in a significant decrease of spermatogenesis and
      azoospermia in 13/14, 11/12, and 12/14 men in groups I to III, respectively. The
      remaining men all had less than 1 million sperm/ml. Reversible side effects
      included increase in body weight, erythrocytes, hemoglobin, and hematocrit and
      decrease in high-density lipoprotein cholesterol and alkaline phosphatase in all
      groups and increase in liver enzymes in the oral NETA group. This study documents
      the high efficacy of TU in combination with NET and confirms that this dose and
      mode of application (1000 mg TU im every 6 wk plus 400 mg NETE im every 6 wk or
      plus 10 mg daily oral NETA) is as effective as the previously reported regimen
      containing 1000 mg TU + 200 mg NETE im every 6 wk. The contraceptive efficacy of
      this combination of TU and NETE should be evaluated in further clinical trials.

PMID- 11836282
TI  - Leptin concentrations in GH deficiency: the effect of GH insensitivity.
AB  - Disorders of GH secretion are known to impair the physiological lipostat and to
      affect the secretion of leptin, a sensitive marker of regional fat accumulation
      and total body composition. In both children and adults with GH deficiency (GHD),
      leptin levels are increased proportionately with enhanced adiposity. In GHI,
      mutations of the GH receptor gene result in a phenotype similar to GHD, with
      increased adiposity and unfavorable lipid profiles. To examine the impact of
      different forms of growth disorders on leptin production, we measured leptin
      levels in 22 GHI patients homozygous for the E180 splice mutation (15 females and
      7 males, aged 8-37 yr) and compared results with those obtained in 20 subjects
      heterozygous for the mutation (11 females and 9 males, aged 7-54), 17 idiopathic
      GHD patients (6 females and 11 males, aged 3-34), and 44 normal subjects (25
      females and 19 males, aged 7-45). After the baseline evaluation, all subjects
      received two 7-d GH treatments at doses of 0.025 and 0.050 mg/kg x d in random
      order. Leptin, IGF-I, and IGF-binding protein-3 (IGFBP-3) were assayed by
      specific immunoassays. IGF-I and IGFBP-3 levels were significantly lower (P <
      0.0001) in homozygous GHI and GHD patients compared with either controls or GHI
      heterozygotes. Circulating leptin levels were significantly higher in homozygous
      GHI patients than in normal controls (20.7 +/- 4.2 vs. 8.7 +/- 1.4 microg/liter)
      as well as when compared with heterozygous GHI subjects (14.4 +/- 3.4
      microg/liter) and GHD patients (9.8 +/- 1.6 microg/liter; P < 0.01). Similar
      results were obtained when leptin was normalized for body mass index. When
      subjects were subgrouped by gender, leptin levels were significantly higher (P <
      0.05) in GHI females than in females of all other groups and were significantly
      increased in GHD males (P < 0.01 vs. control males). Within the study groups,
      females had significantly higher leptin levels than males in controls (12.7 +/- 2
      vs. 3.3 +/- 1 microg/liter; P < 0.001) and homozygous GHI patients (28.7 +/- 5.3
      vs. 6.9 +/- 2.3 microg/liter; P < 0.05), but not in heterozygous GHI (20.1 +/-
      5.4 vs. 7.3 +/- 2.4 microg/liter; P < 0.06) and GHD (10.9 +/- 2.6 vs. 9.2 +/- 2.1
      microg/liter) patients. By multivariate analysis, log-normalized leptin levels
      were best predicted by gender and body mass index in homozygous GHI patients as
      well as in normal subjects. During the 1-wk courses of GH therapy, serum IGF-I
      and IGFBP-3 levels significantly increased (P < 0.0001) in GHD patients,
      heterozygous GHI patients, and control subjects at both GH doses. Inversely,
      leptin levels did not change significantly during either course of GH
      administration in the groups examined. These data demonstrate that leptin is
      increased in patients affected with long-standing homozygous GHI, probably
      reflecting abnormalities of body composition and metabolism typical of this
      condition.

PMID- 11836283
TI  - Effects of testosterone plus medroxyprogesterone acetate on semen quality,
      reproductive hormones, and germ cell populations in normal young men.
AB  - Testosterone (T) treatment suppresses gonadotropin levels and sperm counts in
      normal men, but the addition of a progestin may improve the efficacy of hormonal
      contraception. This study aimed to investigate the speed and extent of
      suppression of testicular germ cell number induced by T plus or minus progestin
      treatment and correlate these changes with serum gonadotropins and inhibin B
      levels, testicular androgens, and sperm output. Thirty normal fertile men (31-46
      yr) received either testosterone enanthate (TE, 200 mg im weekly) alone or TE
      plus depot medroxyprogesterone acetate (DMPA, 300 mg im once) for 2, 6, or 12 wk
      (n = 5 per group) before vasectomy and testis biopsy. Five men (controls)
      proceeded directly to surgery. The inclusion of DMPA led to a more rapid fall in
      serum FSH/LH levels (time to 10% baseline: FSH; 12.6 +/- 2.6 vs. 7.9 +/- 1.4 d;
      LH, 9.9 +/- 3.4 vs. 3.4 +/- 1.7 d, TE vs. TE+DMPA, respectively, mean +/- SD,
      both P < 0.0001), yet the mean time to reach a sperm count 10% of baseline was
      not different (23.7 +/- 7.3 vs. 25.3 +/- 13.9 d, NS). The maximum extent of
      FSH/LH suppression was identical at 12 wk (mean serum FSH 1.2 and 1.6%, and mean
      LH 0.3 and 0.2% of baseline: TE vs. TE+ DMPA, respectively) as was sperm count
      suppression (5 of 5 and 4 of 5 men, respectively, with sperm counts < or =0.1 x
      10(6)/ml). Serum inhibin decreased to 55% control at 12 wk in the TE+DMPA group
      (P < 0.05) but was unchanged by TE treatment (86% control, NS). Testicular T
      levels declined to approximately 2% of control levels, but testicular
      dihydrotestosterone and 5alpha-androstane-3alpha,17beta-diol (Adiol) levels were
      not different to control. Germ cell numbers as determined by stereological
      methods did not differ between TE and TE+DMPA except at 2 wk when type B
      spermatogonia and early spermatocytes were significantly lower in the TE+DMPA
      group (P < 0.05). In all groups, a marked inhibition of Apale-->B spermatogonial
      maturation was seen along with a striking inhibition of spermiation. We conclude
      that: 1) the addition of DMPA hastens the onset of FSH/LH suppression,
      correlating with a more rapid impairment of spermatogonial development, but in
      the longer term, neither germ cell number nor sperm count differed; 2) testicular
      dihydrotestosterone and Adiol levels are maintained during FSH/LH suppression
      despite markedly reduced T levels suggesting up-regulation of testicular 5alpha
      reductase activity; and 3) spermatogonial inhibition is a consistent feature, but
      spermiation inhibition is also striking and is an important determinant of sperm
      output.

PMID- 11836285
TI  - A population-based study on the frequency of additional congenital malformations
      in infants with congenital hypothyroidism: data from the Italian Registry for
      Congenital Hypothyroidism (1991-1998).
AB  - In the last decade a high frequency of other congenital anomalies has been
      reported in infants with congenital hypothyroidism (CH) detected by neonatal
      screening. In the present study the occurrence of additional congenital
      malformations (CM) in the population of CH infants detected in Italy between 1991
      and 1998 (n = 1420) was investigated. In Italy all of the centers in charge of
      screening, treatment, and follow-up of CH adhere to the Italian National Registry
      of infants with CH. In this study a high prevalence of additional CM (8.4%), more
      than 4-fold higher than that reported in the Italian population (1-2%), was found
      in the population of CH infants. Cardiac anomalies represented the most frequent
      malformations associated with CH, with a prevalence of 5.5%. However, a
      significant association between CH and anomalies of nervous system, eyes, and
      multiple CM was also observed. In conclusion, the significantly higher frequency
      of extrathyroidal congenital malformations reported in the CH infants than in the
      general population represents a further argument supporting the role of a genetic
      component in the etiology of CH. Investigations of the molecular mechanisms
      underlying developmental events of formation of thyroid and other organs
      represent critical steps in the knowledge of CH etiology.

PMID- 11836286
TI  - Atorvastatin lowers C-reactive protein and improves endothelium-dependent
      vasodilation in type 2 diabetes mellitus.
AB  - Endothelial dysfunction is frequently found in diabetic subjects. This study was
      performed to investigate whether atorvastatin therapy was able to reverse
      endothelial dysfunction in type 2 diabetes and, if so, whether the effect was due
      to its antiinflammatory action. Eighty patients (baseline low density
      lipoprotein, 4.37 +/- 0.71 mmol/liter) were randomized to atorvastatin (10 mg
      daily for 3 months, followed by 20 mg daily for 3 months) or placebo in a double
      blind study. Endothelial function was assessed by high resolution vascular
      ultrasound, and high sensitivity C-reactive protein (CRP) was assessed by
      immunoturbidimetric assay. Diabetic patients had higher CRP (P < 0.01) than
      matched nondiabetic controls, and both endothelium-dependent and independent
      vasodilation were impaired (P < 0.01). Atorvastatin (10 and 20 mg) lowered plasma
      cholesterol by 32.9% and 38.0%, triglyceride by 15.4% and 23.1%, and low density
      lipoprotein by 43.4% and 50.1%, respectively. At 6 months, plasma CRP decreased
      in the atorvastatin group compared with baseline (P < 0.05). Endothelium
      dependent vasodilation improved in the atorvastatin group compared with the
      placebo group (P < 0.05). The percent change in endothelium-dependent
      vasodilation at 6 months correlated with the percent change in CRP (r = -0.44; P
      < 0.05), but not with changes in plasma lipids. In conclusion, treatment with
      atorvastatin in type 2 diabetes led to a significant improvement in endothelium
      dependent vasodilation, which might be partly related to its anti-inflammatory
      effect.

PMID- 11836287
TI  - Ovarian function and metabolic factors in women with oligomenorrhea treated with
      metformin in a randomized double blind placebo-controlled trial.
AB  - Women with oligomenorrhea and polycystic ovaries show a high incidence of
      ovulation failure perhaps linked to insulin resistance and related metabolic
      features. A number of reports show that the biguanide metformin improves ovarian
      function. However, in these trials the quality of evidence supporting ovulation
      is suboptimal, and few studies have been placebo-controlled. The aim of our study
      was to use a double-blind, placebo-controlled approach with detailed assessment
      of ovarian activity (two blood samples per week) to assess the validity of this
      therapeutic approach in this group of women. Of the 94 patients randomized, 2
      withdrew before treatment commenced, 47 received placebo, and 45 received
      metformin (850 mg, twice a day). The numbers discontinuing the study prematurely
      were higher in the treatment group (n = 15) than the placebo group (n = 5; P <
      0.05). The ovulation frequency assessed by the ratio of luteal phase weeks to
      observation weeks was significantly (P < 0.01) higher in the treated group (23%)
      compared with the placebo (13%), and the time to first ovulation was
      significantly (P < 0.05) shorter [23.6 d; 95% confidence interval (CI), 17, 30;
      compared with 41.8 d; 95% CI, 28, 56]. The proportion of patients failing to
      ovulate during the placebo-treatment period was higher (P < 0.05) in the placebo
      group, and the majority of ovulations were characterized by normal progesterone
      concentrations in both groups. The effect of metformin on follicular maturation
      was rapid, because the E2 circulating concentration increased over the first week
      of treatment only in the metformin group. Significant (P < 0.01) weight loss (and
      leptin reduction) was recorded in the metformin group, whereas the placebo group
      actually increased weight (P < 0.05). A significant increase in circulating high
      density lipoprotein was observed only in the metformin-treated group. Metabolic
      risk factor benefits of metformin treatment were not observed in the morbidly
      obese subgroup of patients (body mass index > 37). No change in fasting glucose
      concentrations, fasting insulin, or insulin responses to glucose challenge was
      recorded after 14-wk metformin or placebo therapy. There was an inverse
      relationship between body mass and treatment efficacy. We show in a large
      randomized placebo-controlled trial that metformin treatment improves ovulation
      frequency in women with abnormal ovarian function and polycystic ovaries
      significantly but to a modest degree, and protracted treatment improves
      cardiovascular risk factors. These data support a beneficial effect of metformin
      in improving ovarian function in women with oligomenorrhea and polycystic
      ovaries.

PMID- 11836288
TI  - Thyroid developmental anomalies in first degree relatives of children with
      congenital hypothyroidism.
AB  - Congenital hypothyroidism (CH) is most frequently caused by thyroid developmental
      abnormalities and it has recently been seen to have a familial component. The aim
      of this study was to investigate whether thyroid developmental abnormalities
      exist in first degree relatives of CH children with thyroid dysgenesis, an
      anomaly which, when present, is sometimes asymptomatic. Thyroid ultrasonography
      and function were evaluated among first degree relatives (n = 241) of 84 isolated
      CH children with thyroid dysgenesis. The results were compared with those of an
      unselected control population (n = 217). In 19 individuals (7.9% of cases)
      belonging to 18 families (21.4%), 21 cases of thyroid developmental abnormalities
      were detected, whereas only 2 subjects (0.9%) were affected in controls (P <
      0.001). These 21 thyroid developmental abnormalities included thyroglossal duct
      cysts (n = 14), additional thyroid tissue with presence of a pyramidal lobe (n =
      3), thyroid hemiagenesis (n = 3), and ectopic thyroid tissue (n = 1). All of
      these subjects showed normal thyroid function and belonged to nuclear families of
      CH children with athyreosis (n = 8), ectopic thyroid tissue (n = 9), or
      hemiagenesis (n = 1). A segregation analysis led to the conclusion that thyroid
      developmental abnormalities are compatible with an autosomal dominant mode of
      inheritance with a low penetrance estimated at 21% for asymptomatic thyroid
      developmental abnormalities and a probability of less than 7% of developing CH
      for a carrier of the susceptibility allele. In conclusion, these observations
      support the hypothesis of a common genetic component of the disorder with
      heterogeneous phenotypes.

PMID- 11836289
TI  - Macroprolactinemia revisited: a study on 106 patients.
AB  - The predominance of high molecular weight PRL, or macroprolactinemia, has long
      been known in hyperprolactinemic patients with maintained fertility. Among 1,106
      consecutive patients investigated for hyperprolactinemia in our center over a 10
      yr period, serum PRL chromatography was performed in 368 cases because of
      discordant clinical, biological, or neuroradiological findings. We prospectively
      studied the 106 patients with macroprolactinemia (96 women, 6 men, 4 children)
      and compared them with the 262 hyperprolactinemic patients with a normal PRL
      elution pattern. We concluded the following: 1) the incidence of
      macroprolactinemia in our hyperprolactinemic population was at least 10%; 2)
      despite preserved fertility with uneventful pregnancies, some of the usual
      symptoms of hyperprolactinemia were present; 3) mean PRL values were 61 +/- 66
      microg/liter (range, 20-663) and exceeded 100 microg/liter in 8.5% of patients;
      4) PRL levels usually remained stable over time; 5) on dopaminergic therapy, PRL
      returned to normal in 21 of 45 treated patients; 6) during follow-up of 7
      pregnancies, PRL increased to supraphysiological levels in 5; and 7) pituitary
      magnetic resonance imaging was normal in 78% of patients or revealed diverse
      pituitary lesions, including adenomas (n = 5). A diagnostic method for
      macroprolactinemia should be available to all centers to avoid unnecessary
      hormonal or radiological investigations and treatments.

PMID- 11836290
TI  - Age trends in the level of serum testosterone and other hormones in middle-aged
      men: longitudinal results from the Massachusetts male aging study.
AB  - We used longitudinal data from the Massachusetts Male Aging Study, a large
      population-based random-sample cohort of men aged 40-70 yr at baseline, to
      establish normative age trends for serum level of T and related hormones in
      middle-aged men and to test whether general health status affected the age
      trends. Of 1,709 men enrolled in 1987-1989, 1,156 were followed up 7-10 yr
      afterward. By repeated-measures statistical analysis, we estimated simultaneously
      the cross-sectional age trend of each hormone between subjects within the
      baseline data, the cross-sectional trend between subjects within the follow-up
      data, and the longitudinal trend within subjects between baseline and follow-up.
      Total T declined cross-sectionally at 0.8%/yr of age within the follow-up data,
      whereas both free and albumin-bound T declined at about 2%/yr, all significantly
      more steeply than within the baseline data. Sex hormone-binding globulin
      increased cross-sectionally at 1.6%/yr in the follow-up data, similarly to
      baseline. The longitudinal decline within subjects between baseline and follow-up
      was considerably steeper than the cross-sectional trend within measurement times
      for total T (1.6%/yr) and bioavailable T (2-3%/yr). Dehydroepiandrosterone,
      dehydroepiandrosterone sulfate, cortisol, and estrone showed significant
      longitudinal declines, whereas dihydrotestosterone, pituitary gonadotropins, and
      PRL rose longitudinally. Apparent good health, defined as absence of chronic
      illness, prescription medication, obesity, or excessive drinking, added 10-15% to
      the level of several androgens and attenuated the cross-sectional trends in T and
      LH but did not otherwise affect longitudinal or cross-sectional trends. The
      paradoxical finding that longitudinal age trends were steeper than cross
      sectional trends suggests that incident poor health may accelerate the age
      related decline in androgen levels.

PMID- 11836292
TI  - Final height gain by GH therapy in children with idiopathic short stature is dose
      dependent.
AB  - Recombinant human GH therapy to children with idiopathic short stature (ISS)
      increases growth velocity, but its effect on final height (FH) is still
      uncertain. The aim of this study was to investigate the effect of recombinant
      human GH on FH of patients with ISS who were treated according to two protocols
      in comparison to untreated historical controls. In study 1 (n = 24), all patients
      were treated with 14 IU (4.6 mg)/m(2) body surface x wk in the first year;
      thereafter the dosage was doubled if the growth response was insufficient. In
      study 2 (n = 34), patients were randomized into three arms: 18 IU (6 mg)/m(2) x
      wk; 27 IU (9 mg)/m(2) x wk; and 18 IU/m(2) x wk in the first year, followed by 27
      IU/m(2) x wk thereafter. Observed or estimated FH was available for 53 patients.
      Thirty-four untreated controls from the same centers were available for
      comparison. Mean FH SD score in GH-treated children was -2.1, vs. -2.4 in
      controls (-2.4) (NS), but height SD score gain (1.3 vs. 0.7) and the difference
      between FH and predicted adult height (4.0 vs. 0.8 cm) were significantly
      greater. The growth response on an initial dosage of 27 IU/m(2) x wk (6.9 cm) was
      significantly better than on other regimens (2.8 cm). We conclude that a GH
      dosage of 27 IU (9 mg)/m(2) x wk to prepubertal children with ISS leads to a mean
      FH gain of approximately 7 cm, whereas regimens starting on lower dosages are
      less efficacious.

PMID- 11836291
TI  - Changes in body composition during androgen deprivation therapy for prostate
      cancer.
AB  - The aim of this study was to determine the effects of initial treatment with a
      GnRH agonist on body composition in asymptomatic men with nonmetastatic prostate
      cancer. Forty men with locally advanced, node-positive or biochemically recurrent
      prostate cancer, no radiographic evidence of metastases, and no prior androgen
      deprivation therapy were treated with leuprolide 3-month depot 22.5 mg im every
      12 wk for 48 wk. The main outcome measures were percentage changes in weight,
      percentage fat body mass, percentage lean body mass, fat distribution, and muscle
      size after 48 wk. Thirty-two subjects were evaluable. Serum T concentrations
      decreased by 96.3% plus or minus 0.4% (P < 0.001). Weight increased by 2.4% plus
      or minus 0.8% (P = 0.005). Percentage fat body mass increased by 9.4% plus or
      minus 1.7% (P < 0.001), and percentage lean body mass decreased by 2.7% plus or
      minus 0.5% (P < 0.001). Cross-sectional areas of the abdomen and abdominal sc fat
      increased by 3.9% plus or minus 1.2% (P = 0.003) and 11.1% plus or minus 3.4% (P
      = 0.003), respectively. In contrast, the cross-sectional area of intraabdominal
      fat did not change significantly (P = 0.94). Cross-sectional paraspinal muscle
      area decreased by 3.2% plus or minus 1.3% (P = 0.02). GnRH agonists increase
      weight and percentage fat body mass and decrease percentage lean body mass and
      muscle size in men with nonmetastatic prostate cancer. Increased fatness resulted
      primarily from accumulation of sc rather than intraabdominal adipose tissue.

PMID- 11836293
TI  - Genetic heterogeneity in familial renal magnesium wasting.
AB  - Isolated hereditary renal magnesium (Mg) wasting may result from mutations in the
      renal tubular epithelial cell tight junction protein paracellin-1 gene or the
      tubular Na(+),K(+)-ATPase gamma-subunit gene FXYD2. The FXYD2 gene mutation was
      discovered in two Dutch families as an autosomal dominant disorder. It is
      characterized by isolated renal Mg wasting with resultant symptomatic
      hypomagnesemia. The defective FXYD2 gene in these families mapped to chromosome
      11q23. Here, we describe an American family with a similar phenotype but without
      linkage to the 11q23 locus; in testing 22 individuals in the pedigree multipoint
      LOD scores for five different loci from the 11q23 region were equal to -2.97.
      Compared with unaffected family members and normal controls, affected family
      members harbored significant reductions in the serum and lymphocyte Mg
      concentrations and in the serum immunoreactive PTH level with a 4-fold increase
      in the mean fractional urinary Mg excretion rate during a normomagnesemic clamp.
      Bone mineral density at the lumbar spine and proximal femur was significantly
      reduced in affected family members. In conclusion, our data demonstrate locus
      heterogeneity for the phenotype of isolated renal Mg wasting with hypomagnesemia
      and suggest that hypomagnesemia, at least in this pedigree, may be associated
      with low bone mass.

PMID- 11836295
TI  - Sympathoadrenal counterregulation in patients with hypothalamic
      craniopharyngioma.
AB  - In humans, the role of hypothalamic centers for activation of counterregulatory
      release of catecholamines and glucagon during hypoglycemia is unclear. To address
      this question, we investigated the counterregulatory response to acute insulin
      induced hypoglycemia of glucagon, epinephrine, and norepinephrine in eight
      patients who had undergone transcranial surgery for a craniopharyngioma extending
      to the hypothalamic region. We compared the patients' responses with those of
      four patients suffering from hypopituitarism and of six healthy subjects. After
      the i.v. injection of 0.1 U of human insulin per kg of body weight in the
      patients or 0.15 U in healthy subjects, the plasma glucose concentrations
      decreased to similar minimum levels within 30 min in all three groups. All
      subjects recovered spontaneously from hypoglycemia within 2 h. In five of eight
      craniopharyngioma patients, only a small counterregulatory rise in plasma
      epinephrine (< or =2-fold) and norepinephrine could be observed (P < 0.05 for
      epinephrine and P = 0.22 for norepinephrine vs. healthy controls). During
      hypoglycemia, virtually no adrenergic symptoms (tremor, heart pounding, and
      anxiety) were reported by these five patients, and changes in the heart rate were
      diminished. In three craniopharyngioma patients, the counterregulatory increase
      in catecholamines was unimpaired, adrenergic symptoms were reported and a rise in
      heart rate was observed during hypoglycemia. In all craniopharyngioma patients,
      the counterregulatory glucagon response to hypoglycemia was preserved and
      orthostasis increased both catecholamines and the heart rate similar to in the
      patients with hypopituitarism as well as in the healthy controls. Our results
      demonstrate selective impairment of counterregulatory sympathoadrenal activation
      in patients who had undergone surgery for a craniopharyngioma extending to the
      hypothalamic region. This strongly suggests the involvement of hypothalamic
      centers in hypoglycemia-induced activation of the sympathoadrenal axis in humans.
      It remains unclear as to whether hypoglycemia-induced glucagon secretion is also
      controlled by the hypothalamus. However, a common hypothalamic center controlling
      both counterregulatory catecholamine and glucagon release is unlikely, and
      sympathoadrenal activation is not required for hypoglycemia-induced glucagon
      secretion in humans.

PMID- 11836294
TI  - Autoimmune adrenocortical failure in Norway autoantibodies and human leukocyte
      antigen class II associations related to clinical features.
AB  - Autoimmune destruction of the adrenal cortex is the most common cause of primary
      adrenocortical insufficiency (Addison's disease) in industrialized countries. We
      have investigated a large Norwegian cohort of patients with Addison's disease in
      terms of clinical manifestations, autoantibodies, and human leukocyte antigen
      (HLA) class II haplotypes. The study comprised 94 patients (54 females) of ages 6
      85 yr (mean 45 yr) with, either isolated Addison's disease or part of autoimmune
      polyendocrine syndrome type II. Among those diagnosed before the age of thirty,
      53% were men, while among those diagnosed at 30 or above, 30% were men.
      Altogether 77 (82%) of the 94 patients had autoantibodies against 21-hydroxylase
      (21OH). Thirty-eight of the 40 patients with disease duration 5 yr or less had
      such autoantibodies. This frequency fell to 60% among patients with a disease
      duration greater than 35 yr. Five women had gonadal failure. This failure
      correlated with antibodies against side-chain cleavage enzyme (P = 0.03).
      Antibodies against glutamic acid decarboxylase and IA2 correlated with the
      presence of type 1 diabetes (P < 0.005 and P = 0.003, respectively). The
      frequency of the HLA DRB1*03-DQA1*05-DQB1*02 (DR3-DQ2) and DRB1*04-DQA1*03
      DQB1*0302 (DR4-DQ8) haplotypes were positively correlated to Addison's disease,
      whereas the DRB1*01-DQA1*0101-DQB1*0501 (DR1-DQ5) haplotype was negatively
      correlated. In addition, the DRB1*04 subtype DRB1*0404 was increased among
      Addison patients relative to controls. We verify that autoimmunity is the main
      cause of Addison's disease in our cohort. In younger patients, the disease is
      equally common in men and women. Measurement of autoantibodies against 21OH is a
      valuable tool in establishing the etiological diagnosis, especially in patients
      with a short disease duration. Addison's disease is associated with the DR3-DQ2
      and DR4 (0404)-DQ8 haplotypes. A particularly high risk for disease development
      is observed when these occur in a heterozygous combination (DR3-DQ2/DR4-DQ8).

PMID- 11836296
TI  - Regulation of human adipocyte gene expression by thyroid hormone.
AB  - Thyroid hormones are key regulators of metabolism. In adipose tissue, changes in
      thyroid status result in alterations of lipolytic capacity. The effects of these
      hormones are mediated by thyroid hormone receptors that modulate gene
      transcription. Very few target genes have been identified in adipose tissue. To
      investigate the effect of T(3) on gene expression in human adipocytes, primary
      cultures of human sc adipose tissue explants were treated with T(3). (32)P
      labeled cDNA probes prepared from isolated adipocyte total RNA were hybridized to
      cDNA arrays representing 1,176 genes. Among the statistically significant
      variations in mRNA levels with more than 1.3-fold difference, 13 and 6 genes were
      positively and negatively regulated, respectively (n = 3). The genes encoded
      proteins that were involved in signal transduction, lipid metabolism, apoptosis,
      and inflammatory response. Using RT-competitive PCR, we showed a down-regulation
      of phosphodiesterase 3B, alpha(2A)-adrenergic receptor, and G protein alpha(i2)
      subunit mRNAs, and an up-regulation of beta(2)-adrenergic receptor mRNA. These
      regulations may explain the T(3)-mediated increase in catecholamine-induced
      lipolysis. The down-regulation of sterol regulatory element binding protein-1c, a
      transcription factor controlling lipogenic gene expression, may constitute a link
      between thyrotoxicosis and insulin resistance. Thus, these data suggest that T(3)
      modulates expression of genes with a wide range of function in human adipose
      tissue.

PMID- 11836297
TI  - Analysis of Tg transcripts by real-time RT-PCR in the blood of thyroid cancer
      patients.
AB  - Serum Tg (sTg) assays are sometimes unsatisfactory for monitoring thyroid cancer
      because interference caused by anti-Tg antibodies may reduce the sensitivity of
      the tests during thyroid hormone therapy. We have therefore developed a
      complementary method using real-time quantitative RT-PCR based on the
      amplification of Tg mRNA. Two different pairs of primers were used for the
      determination of the frequency of one of the variants of the alternative splicing
      of Tg mRNA. The frequency of this variant was as high in patients (n = 40) as in
      controls (n = 30), accounting for about 33% of the total Tg mRNA. Using
      appropriate primers, we observed that Tg mRNA values in controls varied according
      to the volume of thyroid tissue and the TSH concentration. The Tg mRNA values
      allowed the definition of a positive cutoff point at 1 pg/microg total RNA. This
      cutoff point, tested on the group of patients treated for thyroid cancer,
      produced fewer false negative results than those obtained with sTg assays. The
      standardized, highly sensitive real-time RT-PCR technique may therefore prove
      useful as a complement to sTg assays, particularly for patients with recurrent
      thyroid cancer receiving T(4) therapy.

PMID- 11836298
TI  - Divergent effects of retinoic acids on the expression of ERalpha and 17beta
      hydroxysteroid dehydrogenase type 2 in endometrial carcinoma cells (RL 95-2).
AB  - The effects of E2 are dependent on ERs and local E2 concentration in target
      cells. Modulation of intracellular E2 concentration involves the action of 17beta
      hydroxysteroid dehydrogenase (17HSD) type 2, the enzyme converting E2 to estrone.
      In the present study, the influence of RAs on the growth of endometrial cancer
      cell line RL 95-2 as well as the expression of ERs and 17HSD type 2 have been
      investigated. It was found that RAs repress the growth of RL 95-2 cells, which
      express all subtypes of RXR and RAR, as examined by RT-PCR. Also, quantitative RT
      PCR analysis showed that both ERalpha and ERbeta are present in RL 95-2 cells,
      and Western blot assay further revealed that ERalpha expression was decreased by
      all trans-RA treatment. In contrast, RAs induced 17HSD type 2 mRNA expression in
      a dose- and time-dependent fashion. This stimulatory effect was also detected at
      the level of in vivo oxidative 17HSD activity in cultured cells. On the other
      hand, the abundance of 17HSD type 2 mRNA was not altered by RAs in cultured
      normal epithelial cells isolated from human early- and late-secretory
      endometrium. The data indicate that RAs have an inhibitory effect on the growth
      of RL 95-2 cells and a cross-talk with the estrogen pathway in estrogen
      responsive endometrial cancer cells.

PMID- 11836299
TI  - Role of calpain-10 gene variants in familial type 2 diabetes in Caucasians.
AB  - The calpain-10 gene (CAPN10) has been implicated in type 2 diabetes (T2DM)
      susceptibility by both linkage and association in a Hispanic population from
      Starr County Texas. Common intronic variants seem to alter CAPN10 mRNA levels and
      were associated with insulin resistance but not diabetes in Pima Indians. The
      role of these variants in Caucasian populations is less clear. We found some
      evidence for linkage of T2DM to chromosome 2q approximately 20 cM proximal to the
      NIDDM1/CAPN10 locus. To test the hypothesis that CAPN10 is a diabetes
      susceptibility locus in Caucasian families at high risk for T2DM, we examined the
      influence of the three previously implicated CAPN10 variants on both diabetes
      risk and measures of insulin sensitivity and glucose homeostasis. We genotyped
      approximately 700 members of 63 families for 3 variants (SNP-43, SNP-19, and SNP
      63). We tested each variant separately and as haplotype combinations for altered
      transmission from parents to affected children (transmission disequilibrium
      test), and we tested for an effect of each variant individually on measures of
      glucose and insulin during a glucose tolerance test in nondiabetic family
      members. Finally, we looked for an effect of each variant on measures of insulin
      sensitivity (S(I)) and insulin secretion estimated by frequently sampled iv
      glucose tolerance test and Minimal Model analysis. We could not confirm an
      increase in risk for T2DM susceptibility for any variant or for any haplotype
      combination, although we found marginal evidence for an increased risk of the
      111/221 haplotype combination (P = 0.036) after ascertainment correction.
      However, both SNP-19 and SNP-63 increased fasting and/or postchallenge insulin
      levels, consistent with reduced insulin sensitivity. Furthermore, SNP-19 had
      modest effects on insulin sensitivity measured by homeostatic model, and on
      postchallenge glucose. The reduction in insulin sensitivity was confirmed by
      analysis of the subset of individuals who underwent iv glucose tolerance tests,
      where SNP-19 significantly altered the insulin sensitivity index. CAPN10 cannot
      be considered a major diabetes susceptibility gene in our population and seems
      unlikely to explain the observed linkage findings. However, CAPN10 influences
      insulin sensitivity and glucose homeostasis in nondiabetic members of kindreds at
      high risk for T2DM.

PMID- 11836300
TI  - Brain-derived neurotrophic factor: a novel human ovarian follicular protein.
AB  - Neurotrophins are a family of soluble polypeptide growth factors widely
      recognized for their roles in the mammalian nervous system. One such
      neurotrophin, brain-derived neurotrophic factor (BDNF) was originally described
      in the nervous system but has now been shown to be expressed in a variety of
      nonneuronal tissues including endocrine tissues. We examined the human ovarian
      follicle for its possible secretion of BDNF and further studied mouse oocytes to
      determine BDNF's possible influence upon oocyte maturation. In a series of
      experiments derived from human specimens from in vitro fertilization following
      oocyte retrieval, BDNF was detected in human follicular fluid. To define the
      source of BDNF, cumulus granulosa cells (the cells that immediately surround the
      developing oocyte) were grown in cell culture for 1-2 d. BDNF protein increased
      over 24 h in the culture medium. Moreover, the release of BDNF was enhanced upon
      stimulation with cAMP or forskolin, an activator of cAMP. In contrast, mural
      granulosa (cells lining the follicle), oocytes, and embryos did not release
      appreciable quantities of BDNF. To examine possible targets of BDNF, mouse
      studies were used to localize the BDNF receptor, Trk B, immunocytochemically. The
      receptor was present on the surface of isolated oocytes. Moreover, BDNF promoted
      mouse oocyte maturation in culture. These experiments demonstrate for the first
      time the presence and secretion of BDNF from follicular cells in the human ovary
      and suggest a possible role for BDNF in the regulation and modulation of oocyte
      maturation.

PMID- 11836301
TI  - Insulin resistance is associated with increased circulating level of thrombin
      activatable fibrinolysis inhibitor in type 2 diabetic patients.
AB  - Hypofibrinolysis is a common finding in patients with diabetes mellitus (DM) and
      obesity and a risk factor for the development of cardiovascular disease.
      Recently, a new potent inhibitor of fibrinolysis, the thrombin-activatable
      fibrinolysis inhibitor (TAFI) has been isolated and characterized from human
      plasma. The present study was undertaken to assess the activity and circulating
      level of TAFI and its relation to fibrinolytic function and obesity in patients
      with type 2 DM. Fifty-seven patients with type 2 DM (38 men, 19 women) were
      enrolled in this study. DM patients were categorized in age-matched obese [body
      mass index (BMI) > or = 25] and nonobese (BMI < 25) groups. The plasma
      concentration and activity of TAFI were significantly (P < 0.05) higher in DM
      patients than in healthy controls. The plasma levels and activity of TAFI were
      significantly (P < 0.05) elevated in obese DM patients compared with nonobese DM
      and nonobese healthy subjects. RT-PCR demonstrated the expression of TAFI in
      human adipose tissue and in human endothelial cells. The plasma levels of TAFI
      were independently and significantly correlated with glucose intolerance
      (HbA(1c)), with obesity (BMI, visceral fat area), and with an indicator of
      insulin resistance (glucose infusion rate). This study showed that increased
      circulating level of TAFI may be an important causative factor of
      hypofibrinolysis in patients with type 2 diabetes, obesity and insulin
      resistance.

PMID- 11836302
TI  - Increased bone resorption in moderate smokers with low body weight: the Minos
      study.
AB  - Tobacco was found to be a risk factor for osteoporosis, mainly in postmenopausal
      women. We studied the effect of smoking on bone mineral density (BMD) and bone
      turnover in a cohort of 719 men, aged 51-85 yr, composed of 83 current smokers,
      405 former smokers, and 231 men who never smoked. Most current and former smokers
      were moderate smokers (median, 10 cigarettes/d). Current smokers were younger,
      thinner, and drank more coffee and more alcoholic beverages. After adjustment for
      age, body weight, alcohol intake, and caffeine intake, current and former smokers
      had similar BMD, except at the forearm. Former smokers had lower BMD compared
      with never-smokers at most skeletal sites. Men who had smoked more than 7120
      packs (third quartile) had lower BMD of total hip (P < 0.01) and distal forearm
      (P = 0.03) compared with men in the 2 lower tertiles. In the 3 groups, levels of
      bone formation markers did not differ. After adjustment for confounding
      variables, levels of urinary markers of bone resorption (beta-isomerized C
      terminal telopeptide, free and total deoxypyridinoline) were higher in the
      current smokers than in former smokers and never-smokers. Concentrations of T,
      total 17beta-E2, and androstenedione were higher, whereas that of 25
      hydroxyvitamin D was lower, in current smokers. When men were divided according
      to tertiles of body weight, increased bone resorption, decreased BMD and
      biochemical indexes of secondary hyperparathyroidism were observed in current
      smokers in the lowest tertile of body weight (<75 kg) compared with the never
      smokers, but not in men in the two highest tertiles of body weight. Current
      smokers had a higher prevalence of vertebral deformities after adjustment for age
      and body weight (13% vs. 5%; P < 0.005). In summary, in moderate smokers with low
      body weight (<75 kg), increased bone resorption, not matched by increased bone
      formation, results in decreased BMD and an increased prevalence of vertebral
      deformities. In this group, low serum 25-hydroxyvitamin D and secondary
      hyperparathyroidism may explain, at least partly, the effect of tobacco on bone
      turnover. In former smokers, bone resorption is not increased, but BMD remains
      lower compared with that in never-smokers.

PMID- 11836303
TI  - Prenatal stress diminishes the cytokine response of leukocytes to endotoxin
      stimulation in juvenile rhesus monkeys.
AB  - This study investigated whether exposing the fetal primate to repeated episodes
      of maternal stress would have long-lasting effects on the endotoxin-induced
      cytokine response and corticosteroid sensitivity of peripheral blood cells in
      juvenile animals. Pregnant rhesus monkeys were acutely aroused on a daily basis
      for 6 wk using an acoustical startle protocol, either early or late in the 24-wk
      pregnancy. To quantify cytokine responses and corticosteroid sensitivity in their
      offspring at 2 yr of age, whole blood cultures were stimulated with
      lipopolysaccharide and incubated with dexamethasone (DEX). TNFalpha and IL-6
      levels were determined in the culture supernatants. The blood samples were
      collected from undisturbed monkeys under baseline conditions, as well as in an
      aroused state induced by a 2 h social separation. Juvenile monkeys from stressed
      pregnancies had significantly lower cellular cytokine responses compared with the
      undisturbed controls. When DEX was added to the cell cultures, it systematically
      inhibited TNFalpha and IL-6 production, bringing the values for control animals
      down into the range of the prenatally stressed animals. Lipopolysaccharide
      induced cytokine production was also markedly suppressed by the experience of
      acute stress, reducing cytokine responses of controls to the levels found for
      prenatally disturbed monkeys under baseline conditions. Therefore, this study has
      demonstrated that prenatal disturbance can induce a lasting change in cytokine
      biology, which persists well beyond the fetal and infant stage. Further, these
      effects may be due to elevated hypothalamic-pituitary-adrenal activity in the
      prenatally stressed animals, because both DEX and acute arousal made the cells
      from control monkeys appear more similar to those from disturbed pregnancies.

PMID- 11836304
TI  - Genetics of serum dehydroepiandrosterone sulfate and its relationship to insulin
      in a population-based cohort of twin subjects.
AB  - Previous studies have shown a significant effect of insulin administration on
      serum dehydroepiandrosterone sulfate (DHEA-S) concentration and its metabolic
      rate, with evidence for the effect in men, but not in women. This could lead to
      differences in the sources of variation in serum DHEA-S between men and women and
      in its covariation with insulin concentration. This study aimed to test whether
      these hypotheses were supported in a sample of healthy adult twins. Serum DHEA-S
      (n = 2287) and plasma insulin (n = 2436) were measured in samples from adult male
      and female twins recruited through the Australian Twin Registry. Models of
      genetic and environmental sources of variation and covariation were tested
      against the data. DHEA-S showed substantial genetic effects in both men and women
      after adjustment for covariates, including sex, age, body mass index, and time
      since the last meal. There was no significant phenotypic or genetic correlation
      between DHEA-S and insulin in either men or women. Despite the experimental
      evidence for insulin infusion producing a reduction in serum DHEA-S and some
      effect of meals on the observed DHEA-S concentration, there were no associations
      between insulin and DHEA-S at the population level. Variations in DHEA-S are due
      to age, sex, obesity, and substantial polygenic genetic influences.

PMID- 11836305
TI  - Estrogen mini-dose replacement during GnRH agonist therapy in central precocious
      puberty: a pilot study.
AB  - During GnRH agonist therapy of patients with central precocious puberty (CPP),
      growth is sometimes suppressed to subnormal velocity. The working hypotheses were
      that estrogen levels are suppressed by GnRH agonist therapy below normal
      prepubertal levels, that such suppression is responsible for the slow growth of
      girls with CPP during GnRH agonist therapy, and that a mini-dose of estrogen
      replacement will normalize growth. The present pilot study examined growth and
      bone maturation over 2 yr in 13 patients with CPP and compared therapy with a
      combination of GnRH agonist and 8 microg conjugated equine estrogen (group 1) to
      therapy with GnRH agonist alone (group 2). Both groups had adequate suppression
      of gonadotropins, and E2 levels were below detection levels of our assay
      throughout the study period. Group 2 patients decreased their growth velocity
      from 2.0 +/- 1.4 to -1.6 +/- 1.2 SD score compared with group 1, who maintained
      their growth velocity of 1.3 +/- 1.5 SD score and their height SD score for 2 yr
      (P < 0.01). In group 1 patients the ratio of the change in bone age/change in
      chronological age decreased from 1.2 +/- 0.7 to 0.75 +/- 0.3, and in group 2
      patients it decreased to 0.6 +/- 0.3 and 0.4 +/- 0.2 (P < 0.05) during the first
      and second years of therapy, respectively. It is concluded on a pilot basis that
      estrogen suppression is responsible for the slow growth of girls with CPP during
      GnRH agonist therapy and that a mini-dose of estrogen replacement is safe and
      effective for at least 24 months in maintaining normal prepubertal growth without
      acceleration of bone maturation or pubertal development. The current pilot
      results do not suggest an indication or provide a justification for such therapy.

PMID- 11836307
TI  - Development of pituitary-adrenal endocrine function in the marmoset monkey:
      infant hypercortisolism is the norm.
AB  - Early life stress, involving activation of the hypothalamic-pituitary-adrenal
      (HPA) system, is associated with altered functioning of stress-related systems in
      adulthood. In the rat, postnatal development is characterized by low basal HPA
      activity and stress hyporesponsiveness, and infant exposure to atypical
      glucocorticoid levels leads to chronic alteration of HPA function and HPA
      dependent peripheral and central processes. There have been few studies of
      primate HPA ontogeny, and here we report a study of changes in pituitary-adrenal
      function between birth and adulthood in the common marmoset monkey. In this
      simian primate, basal plasma ACTH and cortisol levels were actually elevated in
      neonates (ACTH, 141 +/- 28 pg/ml; cortisol, 1903 +/- 326 microg/dl) and wk 4
      infants (ACTH, 114 +/- 9 pg/ml; cortisol, 290 +/- 8 microg/dl) relative to month
      2 infants, juveniles (month 6), subadults (month 12), and adults (>2 yr; ACTH, 37
      +/- 4 to 61 +/- 8 pg/ml; cortisol, 101 +/- 2 to 195 +/- 4 microg/dl). In contrast
      to older life stages, neonates lacked circadian change in their plasma cortisol
      levels, and this state of consistently high cortisol was associated with large
      adrenal glands in addition to high ACTH levels. Cerebrospinal fluid cortisol
      levels were, in accord with plasma levels, higher in wk 4 infants than in
      juveniles and subadults. In terms of stress response, month 2 infants
      demonstrated ACTH and cortisol peak stress responses similar to those at older
      life stages (infant stress cortisol, 185 +/- 36% of basal; subadult stress
      cortisol, 174 +/- 6% of basal); whereas infant ACTH recovery was also similar to
      that in older subjects, their cortisol poststress recovery was retarded. This
      primate, it is proposed, provides an excellent complementary model in which to
      test hypotheses derived from the rat model relating to HPA system ontogeny and
      the chronic effects and biomedical implications of hypercorticoidism during early
      life.

PMID- 11836308
TI  - Cortisol/progesterone antagonism in regulation of 15-hydroxysteroid dehydrogenase
      activity and mRNA levels in human chorion and placental trophoblast cells at
      term.
AB  - PGs mediate parturition events. 15-Hydroxyprostaglandin dehydrogenase (PGDH)
      catalyzes the first step in the metabolism of PGs to render them inactive. We
      have reported previously that cortisol (F) decreases PGDH activity and
      progesterone (P(4)) maintains PGDH in human chorion and placenta at term. To
      study the interaction of P(4) and F on the regulation of PGDH, we treated chorion
      and placental trophoblast cells in culture with combinations of F, dexamethasone,
      P(4), trilostane, and medroxyprogesterone acetate (MPA). Following a 24-h steroid
      treatment period and 4-h PGF(2alpha) challenge, culture media and cells were
      collected for measurement of PGF(2alpha) levels and PGDH mRNA by RIA and Northern
      blotting analysis. F and dexamethasone decreased PGDH activity and mRNA levels.
      Exogenous P(4) did not significantly alter PGDH activity or mRNA levels; however,
      MPA significantly stimulated PGDH activity. Trilostane decreased P(4) production
      by more than 90% and also decreased PGDH activity and expression. Coincubation
      with P(4) or MPA reversed trilostane inhibition of PGDH, consistent with a
      stimulatory role for endogenous P(4) on PGDH. MPA significantly reversed F
      inhibition of PGDH activity and mRNA levels. In the presence of trilostane, P(4)
      at equimolar concentration to F reversed F inhibition of PGDH mRNA levels. These
      findings suggest that F may be acting as an endogenous inhibitor of P(4) action
      in the regulation of PGDH at term.

PMID- 11836309
TI  - Endocrine profiles after triggering of final oocyte maturation with GnRH agonist
      after cotreatment with the GnRH antagonist ganirelix during ovarian
      hyperstimulation for in vitro fertilization.
AB  - In a randomized multicenter study, the efficacies of two different GnRH agonists
      were compared with that of hCG for triggering final stages of oocyte maturation
      after ovarian hyperstimulation for in vitro fertilization. Ovarian stimulation
      was conducted by recombinant FSH (Puregon), and the GnRH antagonist ganirelix
      (Orgalutran) was coadministered for the prevention of a premature LH rise. Luteal
      support was provided by daily progestin administration. Frequent blood sampling
      was performed at midcycle in the first 47 eligible subjects included in the
      current study, who were randomized for a single dose of 0.2 mg triptorelin (n =
      17), 0.5 mg leuprorelin (n = 15), or 10,000 IU hCG (n = 15). Serum concentrations
      of LH, FSH, E2, and progesterone (P) were assessed at variable intervals. LH
      peaked at 4 h after both triptorelin and leuprorelin administration, with median
      LH levels of 130 and 107 IU/liter (P < 0.001), respectively. LH levels returned
      to baseline after 24 h. Subjects receiving hCG showed peak levels of 240 IU/liter
      hCG 24 h after administration. A rise in FSH to 19 IU/liter (P < 0.001) was noted
      in both GnRH agonist groups 8 h after injection. Within 24 h the areas under the
      curve for LH and FSH were significantly higher (P < 0.001) in both GnRH agonist
      groups compared with that for hCG. E2 and P levels were similar for all groups up
      to the day of oocyte retrieval. Luteal phase areas under the curve for P and E2
      were significantly elevated (P < 0.001) in the hCG group. The mean (+/-SD)
      numbers of oocytes retrieved were 9.8 +/- 5.4, 8.7 +/- 4.5, and 8.3 +/- 3.3; the
      percentages of metaphase II oocytes were 72%, 85%, and 86%; and fertilization
      rates were 61%, 62%, and 56% in the triptorelin, leuprorelin, and hCG group,
      respectively (P = NS for all three comparisons). These findings support the
      effective induction of final oocyte maturation in both GnRH agonist groups. In
      summary, after treatment with the GnRH antagonist ganirelix for the prevention of
      premature LH surges, triggering of final stages of oocyte maturation can be
      induced effectively by a single bolus injection of GnRH agonist, as demonstrated
      by the induced endogenous LH and FSH surge and the quality and fertilization rate
      of recovered oocytes. Moreover, corpus luteum formation is induced by GnRH
      agonists with luteal phase steroid levels closer to the physiological range
      compared with hCG. This more physiological approach for inducing oocyte
      maturation may represent a successful and safer alternative for in vitro
      fertilization patients undergoing ovarian hyperstimulation.

PMID- 11836310
TI  - PKC-zeta mediates insulin effects on glucose transport in cultured preadipocyte
      derived human adipocytes.
AB  - Insulin-stimulated glucose transport is impaired in the early phases of type 2
      diabetes mellitus. Studies in rodent cells suggest that atypical PKC (aPKC)
      isoforms (zeta, lamda, and iota) and PKB, and their upstream activators, PI3K and
      3-phosphoinositide-dependent protein kinase-1 (PDK-1), play important roles in
      insulin-stimulated glucose transport. However, there is no information on
      requirements for aPKCs, PKB, or PDK-1 during insulin action in human cell types.
      Presently, by using preadipocyte-derived adipocytes, we were able to employ
      adenoviral gene transfer methods to critically examine these requirements in a
      human cell type. These adipocytes were found to contain PKC-zeta, rather than PKC
      lamda/iota, as their major aPKC. Expression of kinase-inactive forms of PDK-1,
      PKC-zeta, and PKC-lamda (which functions interchangeably with PKC-zeta) as well
      as chemical inhibitors of PI 3-kinase and PKC-zeta/lamda, wortmannin and the cell
      permeable myristoylated PKC-zeta pseudosubstrate, respectively, effectively
      inhibited insulin-stimulated glucose transport. In contrast, expression of a
      kinase-inactive, activation-resistant, triple alanine mutant form of PKB-alpha
      had little or no effect, and expression of wild-type and constitutively active
      PKC-zeta or PKC-lamda increased glucose transport. Our findings provide
      convincing evidence that aPKCs and upstream activators, PI 3-kinase and PDK-1,
      play important roles in insulin-stimulated glucose transport in preadipocyte
      derived human adipocytes.

PMID- 11836311
TI  - A single nucleotide polymorphism in protein tyrosine phosphatase PTP-1B is
      associated with protection from diabetes or impaired glucose tolerance in Oji
      Cree.
AB  - Several lines of evidence support a role for protein tyrosine phosphatase 1B (PTP
      1B) in metabolism, and specifically in insulin sensitivity and obesity. We report
      the development of reagents for the amplification and sequencing of the PTP-1B
      gene, which has resulted in the identification of a novel single nucleotide
      polymorphism (SNP), designated 981C-->T. We found a significant association
      between this SNP and the risk of either impaired glucose tolerance (IGT) or type
      2 diabetes in the Oji-Cree of Sandy Lake, Ontario, Canada. Six hundred and fifty
      three subjects were genotyped using PCR amplification of exon 8, followed by
      digestion with the restriction enzyme AvaI. Sixty-eight subjects were
      heterozygotes, and none was a homozygote. Thus, the overall frequencies of the C
      allele and the T allele were 0.948 and 0.052, respectively. Subjects with the PTP
      1B 981T/981C genotype were approximately 40% less likely to have IGT or diabetes
      as subjects with the 981C/981C genotype (P = 0.040). There was no difference in
      quantitative traits among subjects grouped according to the PTP-1B 981C-->T SNP
      genotype. These very preliminary findings suggest that genomic variation in PTP
      1B is associated with a reduced risk of diabetes and are consistent with the idea
      that this protein is important in metabolism.

PMID- 11836312
TI  - Lamin expression in human adipose cells in relation to anatomical site and
      differentiation state.
AB  - Familial partial lipodystrophy-Dunnigan variety (FPLD) is an autosomal dominant
      form of lipodystrophy resulting in a loss of sc fat from the trunk and limbs with
      retention of fat in the visceral depots, face, and neck. Specific point mutations
      in the gene encoding the nuclear lamina proteins, lamins A and C, have been
      established to cause this syndrome. We undertook studies to determine which
      members of the lamin family were expressed in human fat cells, to examine the
      effect of differentiation state on lamin A and C expression in human
      preadipocytes, and to test the hypothesis that regional variation in lamin A/C
      expression might underlie the stereotyped anatomical pattern of FPLD. Lamins A,
      C, and B1, but not B2, were expressed in sc mature human adipocytes. Subcutaneous
      preadipocytes expressed all four lamins, with lamin A and C expression increasing
      with ex vivo differentiation. Consistent with previously reported resistance to
      ex vivo differentiation, omental preadipocytes did not show an increase in lamin
      A or C mRNA under these conditions. Lamin A/C mRNA levels were similar in
      isolated mature adipocytes and preadipocytes from omental, sc, and neck sites.
      However, lamin C was consistently lower, and the ratio of lamin A/C mRNA was
      higher in sc mature adipocytes compared with omental mature adipocytes. We
      conclude that the depot-specific pattern of lamin A/C expression does not provide
      clues to the mechanism of FPLD. Nonetheless, these studies provide new
      information regarding the expression of lamin isoforms in normal human adipose
      cells, which will inform future studies of the molecular pathogenesis of FPLD.

PMID- 11836313
TI  - Using real-time, quantitative PCR for rapid genotyping of the steroid 21
      hydroxylase gene in a north Florida population.
AB  - The most common cause of congenital adrenal hyperplasia is steroid 21-hydroxylase
      deficiency. The molecular genetics of this disease are such that genotyping is a
      potentially useful tool in its diagnosis. An assay was developed using real-time,
      quantitative PCR to detect deletions of the steroid 21-hydroxylase gene
      (CYP21A2). This assay was able to detect heterozygous gene deletions with an
      alpha error rate of less than 5%, with a power greater than 95%. When combined
      with allele-specific PCR, genotyping for the nine most common mutations can be
      completed within hours of blood sampling. This technique was used to study
      subjects with 21-hydroxylase deficiency in North Florida. Twenty-eight subjects
      with congenital adrenal hyperplasia, seven first-degree relatives and thirteen
      normal subjects, were characterized. Of 96 chromosomes, 69 abnormal alleles were
      identified. Among unrelated abnormal alleles, the frequency of specific mutations
      was 28% for a gene deletion, 24% for the intron 2 splice mutation, 10% for
      ile172asn, 8% each for val281leu and the exon 6 cluster, and 6% for gln318x
      mutations. These frequencies, as well as the genotype/phenotype correlation, were
      similar to those found in comparable populations. The utility of genotyping in
      the diagnosis of 21-hydroxylase deficiency is increased by the rapidity of the
      analysis. With quantitative PCR, the need for more expensive and time consuming
      Southern blot analysis is reduced and limited to the clarification of certain
      genotypes. Faster results will allow for more timely initiation of appropriate
      therapy and limit the exposure of potentially unnecessary therapy.

PMID- 11836314
TI  - Altered vascular function in young women with polycystic ovary syndrome.
AB  - Polycystic ovary syndrome (PCOS) is characterized by hyperinsulinemic insulin
      resistance, a metabolic disorder that in other circumstances is associated with
      increased cardiovascular risk. We compared macrovascular and microvascular
      function in 19 women with PCOS with 12 control subjects matched as a group for
      body mass index. Macrovascular function was assessed by recording pulse wave
      velocity (PWV) across the aorta and brachial artery. Microvascular function was
      studied by wire myography, by measuring the concentration response curve to
      norepinephrine (NE) before and after incubation with insulin (100 and 1,000 pM).
      PWV at the level of the brachial artery was found to be significantly elevated in
      the PCOS group [9.08 (range, 8.34-11.15) m/sec(-1) vs. 8.27 (range, 7.5-9.01)
      m/sec(-1); P = 0.03]. In contrast, PWV measured in the aorta did not differ
      between the two groups [7.49 +/- 1.21 vs. 7.84 +/- 1.44 m/sec(-1); P = 0.8]. In
      vessels from control subjects, insulin reduced the contraction response to NE. At
      an insulin concentration of 100 pM, NE negative log EC50 (pD(2)) was 6.2 +/- 0.24
      vs. 6.7 +/- 0.15 (P = 0.02). At a concentration of 1,000 pM, NE pD(2) was 6.4 +/-
      0.14 vs. 6.9 +/- 0.19 (P = 0.0006). Both concentrations also caused attenuation
      in maximal tension developed in response to NE (insulin 100 pM, 12 +/- 3%, P =
      0.002; insulin 1,000 pM, 17 +/- 5%, P = 0.009). In contrast, there was no change
      in the PCOS group with insulin at 100 pM for either pD(2) (6.7 +/- 0.24 vs. 6.8
      +/- 0.27; P = 0.3) or maximum contraction (-0.4 +/- 2%; P = 0.8). At 1,000 pM,
      there was a change in pD(2) (6.4 +/- 0.2 vs. 6.8 +/- 0.2; P = 0.003) but not
      maximum contraction (4 +/- 3%; P = 0.2). In conclusion, this study is the first
      to demonstrate increased vascular stiffness and a functional defect in the
      vascular action of insulin ex vivo in patients with PCOS. We suggest that these
      findings are indicative of insulin resistance at a vascular level in women
      without overt cardiovascular disease.

PMID- 11836315
TI  - L-arginine transport by the microvillous plasma membrane of the
      syncytiotrophoblast from human placenta in relation to nitric oxide production:
      effects of gestation, preeclampsia, and intrauterine growth restriction.
AB  - Nitric oxide (NO) is an important regulator of placental perfusion, and its
      production is dependent on the activity of substrate (L-arginine) transporters.
      In the light of evidence for altered NO production in the feto-placental unit in
      preeclampsia and intrauterine growth restriction (IUGR), we investigated
      gestational changes in human placental L-arginine transport by systems y(+) and
      y(+)L in purified microvillous plasma membrane vesicles. We also examined the
      effect of preeclampsia and IUGR on the activity of these transport systems and
      the relationship between transporter activity and NO production (nitrate/nitrite
      concentrations) in the feto-placental unit. Between first trimester and term,
      there was a significant positive correlation between system y(+) activity and
      gestational age (r = 0.36; P = 0.013; n = 47), but a significant negative
      correlation between system y(+)L activity and gestational age (r = -0.6; P <
      0.0001; n = 47). The activity of these transport systems was not altered in
      preeclampsia or IUGR. In placentas from normal term pregnancies, there was no
      correlation between the activity of microvillous plasma membrane L-arginine
      transporters and nitrate/nitrite concentrations in umbilical venous plasma or
      placental homogenate.

PMID- 11836316
TI  - Identification of the 49-kDa autoantigen associated with lymphocytic hypophysitis
      as alpha-enolase.
AB  - Lymphocytic hypophysitis is part of the spectrum of organ-specific autoimmune
      diseases, and although its histopathology is well documented, its pathogenesis is
      unclear. Serum autoantibodies directed against a 49-kDa cytosolic protein are
      detected by immunoblotting in 70% of patients with biopsy-proven lymphocytic
      hypophysitis. Here we report the purification and identification of this first
      target autoantigen in lymphocytic hypophysitis. The autoantigen has a molecular
      mass of 49 kDa, a cytosolic localization, and a ubiquitous tissue distribution.
      The 49-kDa protein was purified from monkey brain and human placental cytosol.
      Limited amino acid sequencing after proteolytic digestion of the human placental
      protein showed identity with alpha-enolase. The identification was confirmed
      using sera from patients with pituitary autoimmunity, which strongly reacted with
      recombinant human alpha-enolase and yeast enolase, but not with rabbit muscle
      beta- enolase. This indicates that the immunoreactive epitopes are largely
      conserved from yeast to human, but are not present in beta-enolase. alpha-Enolase
      autoantibodies are not specific to pituitary autoimmune disease and have been
      reported in other autoimmune diseases. However, this study is the first to
      indicate a role for alpha-enolase as an autoantigen in lymphocytic hypophysitis.

PMID- 11836317
TI  - Decreased plasma leptin concentrations in tuberculosis patients are associated
      with wasting and inflammation.
AB  - Tuberculosis patients often suffer from severe weight loss, which is considered
      to be immunosuppressive and a major determinant of severity and outcome of
      disease. Because leptin is involved in weight regulation and cellular immunity,
      its possible role in tuberculosis-associated wasting was investigated. In an
      urban clinic in Indonesia, plasma leptin concentrations, indicators of adipocyte
      mass, appetite, C-reactive protein (CRP), tuberculin reactivity, and cytokine
      response were measured in tuberculosis patients and healthy controls. Plasma
      leptin concentrations were lower in patients than in controls (615 vs. 2,550
      ng/liter; P < 0.001). Multivariate regression analysis showed that body fat mass
      and inflammation were two independent factors determining plasma leptin
      concentrations; there was a positive correlation between fat and leptin, whereas,
      unexpectedly, leptin was inversely associated with CRP and tumor necrosis factor
      alpha production. Concentrations of both CRP and leptin were independently
      associated with loss of appetite. Our results do not support the concept that
      weight loss in tuberculosis is caused by enhanced production of leptin. Rather,
      loss of body fat leads to low plasma leptin concentrations, and prolonged
      inflammation may further suppress leptin production. Because leptin is important
      for cell-mediated immunity, low leptin production during active tuberculosis may
      contribute to increased disease severity, especially in cachectic patients.

PMID- 11836318
TI  - Major gender differences in the lipolytic capacity of abdominal subcutaneous fat
      cells in obesity observed before and after long-term weight reduction.
AB  - The influence of obesity on the lipolytic capacity of isolated sc fat cells was
      studied prospectively in 13 women and 10 men, all obese, but otherwise healthy,
      before and 2 and 3 yr after weight reduction by bariatric surgery. Nonobese
      subjects (25 women and 17 men) without a family history of obesity served as the
      control group. Lipolytic capacity was determined after stimulation at different
      steps of the lipolytic cascade with noradrenaline, isoprenaline, forskolin, and
      (Bu)(2)AMP. Bariatric surgery was followed by a marked and similar reduction of
      body mass index and fat cell volume (approximately 40%) in both genders. Before
      weight loss, lipolytic capacity per cell was elevated in obese women and
      decreased to normal levels after weight reduction at 2 and 3 yr. However,
      lipolytic capacity per fat cell surface area was not changed in obese women. In
      obese men, lipolytic capacity per cell was almost the same as in lean men and was
      not influenced by weight reduction. Lipolytic capacity was related to fat cell
      size in women (P = 0.0008; r = 0.58), but not in men (P = 0.67; r = 0.086). The
      protein content of hormone-sensitive lipase, which determines lipolytic capacity,
      was significantly lower in obese men and women and increased slightly after
      weight reduction in men only. Thus, in women, but not in men, the adipocyte
      lipolytic capacity is influenced by obesity and weight reduction, probably due to
      changes in fat cell size. These gender differences are not related to the amount
      of hormone-sensitive lipase protein in adipocytes.

PMID- 11836319
TI  - Insulin resistance is attenuated in women with polycystic ovary syndrome with the
      Pro(12)Ala polymorphism in the PPARgamma gene.
AB  - Polycystic ovary syndrome (PCOS) is common in women of reproductive age and is
      associated with a high risk for development of type 2 diabetes. Insulin
      resistance, a key component in the pathogenesis of PCOS and glucose intolerance,
      is ameliorated by the thiazolidinediones, synthetic ligands for the PPARgamma. In
      the present study we have examined the relationship of the Pro(12)Ala
      polymorphism in the PPARgamma gene (PPARG) to clinical and hormonal features of
      PCOS. Two hundred and eighteen women with PCOS had a 75-g oral glucose tolerance
      test, and blood was obtained for measurement of serum androgen levels. Sixty
      percent of the subjects were Caucasian, 26% were African-American, 6% were
      Hispanic, 6% were South Asian, and 2% were Middle-Eastern. Compared with
      Caucasians, the African-American group had a higher prevalence of diabetes (19%
      vs. 5%, respectively), were more obese (body mass index, 40.9 +/- 1.8 vs. 36.3 +/
      0.8 kg/m(2); P < 0.05), and were more insulin resistant. Twenty-eight of 218
      subjects had the Ala allele, all in the heterozygous state. The frequency of the
      Ala allele varied among the groups: 0.01 in African-Americans, 0.08 in
      Caucasians, and 0.15 in Hispanics. Nondiabetic Caucasians with an Ala allele
      (Pro/Ala group) were more insulin sensitive than those in the Pro/Pro group, as
      evidenced by a lower homeostasis model assessment index (5.18 +/- 1.33 vs. 6.54
      +/- 0.54; P < 0.05) and lower levels of insulin at both the fasting (132 +/- 27
      vs. 165 +/- 12 pmol/liter; P = 0.03) and 2 h (688 +/- 103 vs. 10190 +/- 99
      pmol/liter; P = 0.04) time points during the oral glucose tolerance test. We
      conclude that Pro(12)Ala in PPARG is a modifier of insulin resistance in
      Caucasian women with PCOS.

PMID- 11836320
TI  - Body fat distribution and metabolic derangements in patients with familial
      partial lipodystrophy associated with mandibuloacral dysplasia.
AB  - Mandibuloacral dysplasia (MAD) is a rare autosomal recessive disorder that is
      characterized by mandibular and clavicular hypoplasia, acroosteolysis, delayed
      closure of cranial sutures, joint contractures, and mottled cutaneous
      pigmentation. It is also associated with partial lipodystrophy, but the pattern
      of fat loss has not been well characterized. We studied body fat distribution in
      two male and two female patients with MAD by anthropometry, dual energy x-ray
      absorptiometry, and magnetic resonance imaging. Blood glucose and insulin
      responses during an oral glucose tolerance test and fasting serum lipoproteins
      were determined. Three of the four subjects had loss of sc fat from the
      extremities with normal or slight excess in the neck and truncal regions (termed
      type A pattern). In contrast, one patient had generalized loss of sc fat
      involving the face, trunk, and extremities (type B pattern). All of the patients
      had normal glucose tolerance but had fasting and postprandial hyperinsulinemia
      suggestive of insulin resistance. Elevated serum triglycerides with low high
      density lipoprotein cholesterol levels were noted in three subjects. We conclude
      that familial partial lipodystrophy associated with MAD presents with two types
      of body fat distribution patterns, both of which are associated with insulin
      resistance and its metabolic complications.

PMID- 11836321
TI  - Variable ACTH-stimulated 17-hydroxyprogesterone values in 21-hydroxylase
      deficiency carriers are not related to the different CYP21 gene mutations.
AB  - The currently used cutoff level for ACTH-stimulated 17- hydroxyprogesterone
      (17OHP) for the diagnosis of the nonclassical (NC) form of 21-hydroxylase
      deficiency (21OHD), established before molecular studies, is based on the mean +
      2 SD of 17OHP levels of obligate heterozygotes. However, carriers of CYP21
      mutations present variable ACTH-stimulated 17OHP levels, ranging from normal
      values up to 30 nmol/liter. The aim of this study was to determine whether ACTH
      stimulated 17OHP levels in obligate carriers for 21OHD would be correlated with
      the impairment of the enzyme activity caused by these mutations, which would
      affect the 17OHP cutoff level for the diagnosis of the NC form. Fifty-nine
      parents of patients with the classical and NC forms of 21OHD had their DNA
      screened for the mutations found in the index case and were divided into three
      mutation groups according to the impairment of enzyme activity (A = 0%, B = 3%,
      and C > 20%). All parents carried mutations in one allele (29 of group A, 9 of
      group B, and 21 of group C). Blood samples were collected at baseline condition
      and 60 min after ACTH (250 microg i.v.) to measure 17OHP levels. The levels among
      groups A, B, and C were compared using the Kruskall Wallis test. ACTH-stimulated
      17OHP levels identified 39% of the carriers (9 in group A, 2 in group B and 12 in
      group C). The mean +/- SD basal 17OHP levels in groups A, B, and C were: 2.94 +/-
      1.89, 1.77 +/- 0.81 and 3.90 +/- 2.43 nmol/liter, respectively (P > 0.05) and for
      ACTH-stimulated levels were 12.6 +/- 7.2, 13.2 +/- 12.9 and 16.8 +/- 7.8
      nmol/liter, respectively (P > 0.05). Two carriers presented ACTH-stimulated 17OHP
      levels between 30 and 45 nmol/liter and their entire CYP21 sequencing revealed
      only one mutation in heterozygous state indicating that the current cutoff level
      might overestimate the diagnosis of the NC form. We conclude that the variable
      ACTH-stimulated 17-OHP levels in carriers are not related to CYP21 gene mutations
      with different impairment of enzyme activity.

PMID- 11836323
TI  - A new recombinant cell bioassay for ultrasensitive determination of serum
      estrogenic bioactivity in children.
AB  - The evaluation of estrogenic status is necessary for many physiological and
      pathological conditions in pediatric as well as adult endocrinology. Because
      current immunoassays exclusively measure E2--and with a sensitivity that is
      insufficient for prepubertal children--we developed a new recombinant cell
      bioassay for ultrasensitive determination of serum estrogenic bioactivity. This
      assay is based on human uterine cervix carcinoma cells, HeLa cells, that do not
      naturally express E2 receptor. These cells were transfected with plasmids
      encoding the human ERalpha or beta, along with an estrogen-responsive promoter
      fused to the luciferase gene, and called HELNalpha and HELNbeta for HeLa estrogen
      responsive element luciferase neomycin alpha and beta. HELNalpha and HELNbeta are
      able to respond to estrogens and various compounds having estrogenic activity
      but, because of the importance of ERalpha in the reproductive function, we chose
      to work with the HELNalpha cell line. The luciferase activity we obtained was
      compared with an E2 standard curve specific for each serum sample and established
      with stripped serum. The estrogenic bioactivity was expressed in picograms of E2
      equivalents, and the detection limit was < 1 pg x ml(-1) E2 equivalents. The
      intra and interassay error was lower than 10% and 20%, respectively. We measured
      estrogenic bioactivity in 18 normal prepubertal boys (age = 9.7 +/- 2.4 yr), 18
      normal prepubertal girls (age = 9.2 +/- 1.7 yr) and 18 normal pubertal girls (age
      = 13.6 +/- 1.8 yr). The estrogenic bioactivity in the prepubertal girls was
      significantly higher than in the boys, i.e. 3.53 +/- 2.23 pg x ml(-1) vs. 1.44 +/
      0.87 pg x ml(-1) (P < 0.01). A significant difference was found between the pre-
      and pubertal girls, i.e. 3.53 +/- 2.23 pg x ml(-1) vs. 26.77 +/- 18.32 pg x ml(
      1) (P < 0.01). This ultrasensitive bioassay measures total estrogenic bioactivity
      of serum with very high sensitivity. It has numerous potential applications in
      pediatric and adult endocrinology. In addition, this assay may help to evaluate
      excess estrogenic activity related to aromatase overexpression or contamination
      by environmental chemicals.

PMID- 11836324
TI  - Differential effects of GH replacement on the components of the leptin system in
      GH-deficient individuals.
AB  - GH therapy is associated with a reduction in fat mass and an increase in lean
      mass in subjects with GH deficiency (GHD). Leptin, like GH, plays an important
      role in the regulation of body composition. GH treatment has been shown to reduce
      serum leptin; however, the physiological interactions between the leptin system
      (free leptin, bound leptin, and soluble leptin receptor) and the GH/IGF-I system
      largely remain unknown. Twenty-five patients with childhood (n = 10) and adult
      onset (n = 15) GHD were studied. GH status had previously been determined using
      an insulin tolerance test and/or an arginine stimulation test. The following
      parameters were recorded at baseline (V1) and then after 3 months (V2) and 6
      months (V3) on GH treatment: fat mass, body mass index (BMI), and waist/hip ratio
      (WHR); blood samples were taken after an overnight fast for free leptin, bound
      leptin, soluble leptin receptor, insulin, and IGF-I. At V2 and V3, respectively,
      a fall in free leptin (P < 0.001 for each), and at V3 a fall in in percent fat
      mass (P < 0.001) were observed. There were no significant changes in BMI or WHR.
      Simultaneously, there was a rise in insulin (P = 0.068 and P < 0.001), IGF-I (P <
      0.001 and P < 0.001), bound leptin (P = 0.005 and P < 0.001), and soluble leptin
      receptor (P = 0.61 and P < 0.001). A positive relationship was noted between free
      leptin and BMI (P < 0.001) and between free leptin and fat mass (P < 0.001), and
      a negative relationship was found between free leptin and IGF-I (P < 0.001) and,
      within patient, between free leptin and insulin (P < 0.001). There was no
      significant correlation between free leptin and WHR. Bound leptin had a positive
      association with IGF-I (P < 0.001) and insulin (P = 0.002) and a negative
      relationship with percent fat mass (P = 0.023). Soluble leptin receptor was also
      positively related to IGF-I (P < 0.001). In conclusion, our data suggest that the
      reduction in serum leptin with GH treatment, as noted by others, is mediated
      through a fall in free leptin. The fall in free leptin and in part the rise in
      bound leptin are most likely through a reduction in percent fat mass. However,
      the observed changes in free leptin and bound leptin and, more importantly, the
      rise in soluble leptin receptor, are not explained entirely by modifications in
      body composition and may be a direct result of GH/IGF-I.

PMID- 11836325
TI  - Reduction of plasma leptin levels and loss of its circadian rhythmicity in
      hypocretin (orexin)-deficient narcoleptic humans.
AB  - Recent observations have implicated hypocretin deficiency in the pathogenesis of
      narcolepsy. Hypocretin neurotransmission also affects energy balance, and
      narcoleptic patients tend to become obese. Because hypocretins appear to have
      important neuroendocrine effects, we hypothesized that the neuroendocrine systems
      that regulate energy balance might be distinctly set in narcolepsy. As leptin is
      a pivotal part of these systems, we explored the 24-h plasma leptin (20-min
      sampling interval) concentration profile in six narcoleptic males and six normal
      controls, matched for age, sex, body mass index, waist/hip ratio, and fat mass.
      We thus demonstrated a reduction of the mean 24-h leptin concentration in
      narcoleptics to 52% of that in controls (5.9 microg/liter in narcolepsy vs. 11.4
      microg/liter in controls; P < 0.05). Further, a nocturnal acrophase (clock time
      of the highest concentration), which is typical of normal leptin secretion, was
      observed in controls (mean, 2335 h; 95% confidence interval, 2105-0205 h), but
      not in narcoleptic patients. The mechanisms that potentially disturb the
      circadian rhythm of leptin levels in hypocretin-deficient narcoleptic humans
      include anomalies of the sleep-wake cycle and/or disruption of the circadian
      distribution of autonomic activity. As leptin deficiency clearly leads to morbid
      obesity in experimental animals and humans, we infer that the observed reduction
      of plasma leptin levels may predispose narcoleptic humans to weight gain.

PMID- 11836326
TI  - Concentrations of estrogens and IGFs in umbilical cord blood plasma: a comparison
      among Caucasian, Hispanic, and Asian-American females.
AB  - It has been hypothesized that exposure to elevated levels of estrogens and IGFs
      before birth may increase breast cancer risk in female offspring. We examined
      whether the concentrations of estrone, E2, IGF-I, IGF-II, and IGF-binding protein
      1 (IGFBP-1), -2, and -3 in umbilical cord blood plasma differed in female
      neonates of three racial/ethnic groups with contrasting breast cancer risk. The
      study included 57 Caucasian, 22 Hispanic, and 22 Asian-American subjects.
      Relative contribution of race/ethnicity to the analyte level variability was the
      largest for IGFBP-1 (P = 0.06). The only statistically significant (P < 0.05)
      mean difference was the lower IGFBP-3 levels in Asian than in Caucasian subjects.
      Adjusted mean levels of estrone and E2 for Asian subjects were 128% and 109% of
      the Caucasian means, respectively, whereas the Hispanic group showed lower means
      (85% and 84% of the Caucasian means). IGF-I, IGFBP-1, and IGFBP-3 showed lower
      adjusted means for both Hispanics and Asians compared with Caucasians. However,
      these differences were not statistically significant. In summary, we have shown
      that concentrations of estrogens, IGF-I, IGF-II, and IGFBPs are not different in
      cord blood samples from Caucasian, Hispanic, and Asian-American subjects. These
      data do not support a link between antenatal exposure to elevated levels of
      estrogens and IGFs and breast cancer.

PMID- 11836327
TI  - Characterization of inhibin forms and their measurement by an inhibin alpha
      subunit ELISA in serum from postmenopausal women with ovarian cancer.
AB  - The aim of this study was to characterize the molecular wt forms of inhibins A
      and B and its free alpha-subunit present in serum from women with ovarian cancer
      as a basis for developing improved monoclonal antibody-based inhibin assays for
      monitoring ovarian cancer. Three new inhibin alpha-subunit (alphaC) ELISAs were
      developed using monoclonal antibodies directed to three nonoverlapping peptide
      regions of the alphaC region of the inhibin alpha-subunit. To characterize serum
      inhibin molecular wt forms present in women with ovarian cancer, existing inhibin
      immunoassays (inhibin A, inhibin B, and pro-alphaC) and the new alphaC ELISAs
      were applied to sera from women with granulosa cell tumors and mucinous
      carcinomas previously fractionated using a combined immunoaffinity
      chromatography, preparative SDS-PAGE, and electroelution procedure. The
      distribution and molecular size of dimeric inhibins and alpha-subunit detected
      were consistent with known mol wt forms of inhibins A and B and inhibin alpha
      subunit and their precursor forms present in serum and follicular fluid from
      healthy women. The alphaC ELISAs recognized all known forms of inhibin and the
      free inhibin alpha-subunit, although differences between alphaC ELISAs were
      observed in their ability to detect high mol wt forms. To assess which of the
      alphaC ELISAs was preferred in application to ovarian cancer, the alphaC ELISAs
      were applied to serum from a range of normal postmenopausal women (n = 61) and
      postmenopausal women (n = 152) with ovarian (serous, mucinous, endometrioid,
      clear cell carcinomas, and granulosa cell tumors) and nonovarian (breast and
      colon) cancers. Despite differences in their ability to detect high mol wt forms
      of inhibin, the alphaC ELISAs showed similar sensitivity (i.e. proportion of
      cancer patients correctly detected) and specificity (proportion of controls
      correctly detected) indexes in the detection of mucinous carcinomas (84% and 95%)
      and granulosa cell tumors (100% and 95%) compared with earlier inhibin RIA or
      polyclonal antibody-based immunofluorometric assays. A combination of the alphaC
      ELISAs with the CA125 assay, an ovarian tumor marker that has a high sensitivity
      and specificity for other ovarian cancers (serous, clear cell, and endometrioid),
      resulted in an increase in sensitivity/specificity indexes (95% and 95%) for the
      all ovarian cancer group. These new monoclonal antibody-based inhibin alphaC
      ELISAs now provide practical and sensitive assays suitable for evaluation as
      diagnostic tests for monitoring ovarian cancers.

PMID- 11836328
TI  - Unequal impact of short-term testosterone repletion on the somatotropic axis of
      young and older men.
AB  - The present clinical study compares the impact of low- and high-dose parenteral
      testosterone (T) supplementation on daily GH secretory patterns and serum IGF-I,
      IGFBP-1, and IGFBP-3 concentrations in healthy older (60-82 yr) and young (20-40
      yr) men. To this end, we administered three consecutive weekly injections of
      randomly ordered saline and either a low (100 mg) or a high (200 mg) dose of
      testosterone enanthate im; namely, saline (n = 17, young and n = 16, older), a
      low dose (n = 8 young, n = 8 older) and a high dose (n = 9 young, and n = 8
      older) of androgen. To monitor somatotropic-axis responses, blood was sampled
      every 10 min for 24 h for later chemiluminescence-based assay of serum GH, RIA of
      serum IGF-I, and immunoradiometric assay of serum IGFBP-1 and IGFBP-3
      concentrations. Data were analyzed via a nested analysis of covariance
      statistical design. At baseline (saline injection), older, compared with young,
      men maintained: 1) similar serum total T, IGFBP-1, and IGFBP-3 but reduced IGF-I
      concentrations, namely, mean (+/- SEM) IGF-I 160 plus or minus 15 vs. 280 plus or
      minus 18 microg/liter, (P < 0.001); 2) reduced GH secretory burst mass (0.68 +/-
      0.09 vs. 1.2 +/- 0.20 microg/liter, P = 0.031); 3) more disorderly GH release
      patterns (approximate entropy 0.501 +/- 0.058 vs. 0.288 +/- 0.021, P < 0.001);
      and 4) blunted 24-h rhythmic GH output (nyctohemeral amplitude 0.25 +/- 0.05 vs.
      0.47 +/- 0.08 microg/liter, P = 0.025). Serum T concentrations (ng/dl) did not
      differ in the two age groups supplemented with either a low dose [550 +/- 50
      (young) and 544 +/- 128 (older)] and high [1320 +/- 92 (young) and 1570 +/- 140
      (older)] dose of T. The 100-mg dose of androgen exerted no detectable effect on
      GH secretion in either age cohort but increased the serum IGF-I concentration in
      young men by 20% (P = 0.00098). The 200-mg dose of T failed to alter daily GH
      production in young volunteers but in older men stimulated: 1) a 2.03-fold rise
      in the mean (24-h) serum GH concentration (P = 0.0053, compared with the response
      to saline); 2) a 1.20-fold increase in basal (nonpulsatile) GH production (P =
      0.039); 3) a 2.15-fold amplification of GH secretory burst mass (P = 0.0020); 4)
      a 2.17-fold elevation of the Mesor of nyctohemeral GH output (P = 0.025); 5) a
      1.79-fold enhancement in GH approximate entropy (P = 0.0003); and 6) a 40%
      increase in the fasting serum IGF-I concentration (P = 0.000005). Multivariate
      statistical analysis indicated that following high-dose T administration, the E2
      increment significantly predicted the IGF-I increment in both age groups combined
      (P = 0.003); T dose positively forecast the serum total IGF-I concentration (P =
      0.0031); and age and T dose jointly determined serum LH concentrations (P =
      0.031). In summary, neither a physiological nor a pharmacological dose of T
      administered parenterally for 3 wk augments daily GH secretion in eugonadal young
      men. In contrast, a high dose of aromatizable androgen significantly amplifies 24
      h basal, pulsatile, entropic, and nyctohemerally rhythmic GH production and
      elevates the serum IGF-I concentration in older men. The mechanistic basis for
      the foregoing age-related distinction in GH/IGF-I axis responsivity to T is not
      known.

PMID- 11836329
TI  - Vascular endothelial growth factor: a novel endocrine defensive response to
      hypoglycemia.
AB  - Glucose, the most important fuel for the brain, is supplied by the actions of
      counterregulatory hormones and the sympathetic nervous system. Yet to obtain
      access to the brain, glucose must pass the blood-brain barrier. Here we show that
      vascular endothelial growth factor (VEGF), a potent regulator of blood vessel
      function, is a candidate hormone for facilitating glucose passage across the
      blood-brain barrier under critical conditions. In 16 healthy men, VEGF serum
      concentrations increased under 6 h of insulin-induced hypoglycemic conditions
      from 86.1 +/- 13.4 to 211.6 +/- 40.8 pg/ml (P = 0.002), whereas in the
      hyperinsulinemic euglycemic control condition, no change was observed. During
      hypoglycemia serum VEGF, but no other counterregulatory hormone, was associated
      with preserved neurocognitive function, as measured with a memory test (r =
      0.539; P = 0.031) and the Stroop interference task (r = 0.569; P = 0.021).
      Findings show that acute hypoglycemia is accompanied by a brisk increase in
      circulating VEGF concentration and that VEGF could mediate rapid adaptation of
      the brain to neuroglycopenia.

PMID- 11836330
TI  - Delineation of the molecular defects in the AIRE gene in autoimmune
      polyendocrinopathy-candidiasis-ectodermal dystrophy patients from Southern Italy.
AB  - In this study, we have carried out molecular analysis of the AIRE (autoimmune
      regulator) gene in 11 patients (from 8 families) affected by autoimmune
      polyendocrinopathy-candidiasis-ectodermal dystrophy, originating from a
      restricted area of Southern Italy (the Salento peninsula in Puglia). Of the 16
      mutant AIRE alleles from the 8 probands studied, 12 carried a missense mutation
      (W78R in 9, P539L in 2, and P252L in 1), 2 carried the Q358X nonsense mutation,
      and 2 carried the 1058delT frameshift mutation. All these mutations except the
      1058delT are novel. Each of the detected mutations either predicts a premature
      termination of the protein or results in a nonconservative amino acid change,
      most likely adversely affecting the function of the protein. The W78R missense
      mutation is relatively common in these patients, having been detected (in
      homozygosity or compound heterozygosity) in 6 of the 8 probands tested,
      indicating the presence of a founder effect. The results of this study contribute
      to the delineation of the molecular pathology of the AIRE gene and enhance our
      ability to perform a molecular diagnosis in autoimmune polyendocrinopathy
      candidiasis-ectodermal dystrophy patients from Southern Italy.

PMID- 11836331
TI  - An exon splice enhancer mutation causes autosomal dominant GH deficiency.
AB  - Familial isolated GH deficiency type II (IGHD II) is caused, in some cases, by
      heterogeneous IVS3 mutations that affect GH mRNA splicing. We report here our
      finding an A-->G transition of the fifth base of exon 3 (E3+ 5 A-->G) in affected
      individuals from an IGHD II family. This mutation disrupts a (GAA)(n) exon splice
      enhancer (ESE) motif immediately following the weak IVS2 3' splice site. The
      mutation also destroys an MboII site used to demonstrate heterozygosity in all
      affected family members. To determine the effect of ESE mutations on GH mRNA
      processing, GH(3) cells were transfected with expression constructs containing
      the normal ESE, +5 A-->G, or other ESE mutations, and cDNAs derived from the
      resulting GH mRNAs were sequenced. All ESE mutations studied reduced activation
      of the IVS2 3' splice site and caused either partial E3 skipping, due to
      activation of an E3+ 45 cryptic 3' splice site, or complete E3 skipping. Partial
      or complete E3 skipping led to loss of the codons for amino acids 32-46 or 32-71,
      respectively, of the mature GH protein. Our data indicate that the E3+ 5 A-->G
      mutation causes IGHD II because it perturbs an ESE required for GH splicing.

PMID- 11836333
TI  - Impact of estradiol supplementation on dual peptidyl drive of GH secretion in
      postmenopausal women.
AB  - As an indirect probe of estrogen-regulated hypothalamic somatostatin restraint,
      the present study monitors the ability of short-term oral E2 supplementation to
      modulate GH secretion during combined continuous stimulation by recombinant human
      GHRH [GHRH-(1-44)-amide] and the potent and selective synthetic GH-releasing
      peptide, GHRP-2. According to a simplified tripeptidyl model of GH
      neuroregulation, the effects of estrogen in this dual secretagogue paradigm
      should mirror alterations in endogenous somatostatinergic signaling. To this end,
      seven healthy postmenopausal women underwent frequent (10-min) blood sampling for
      24 h during simultaneous i.v. infusion of GHRH and GHRP-2 each at a rate of 1
      microg/kg x h on d 10 of randomly ordered placebo or 17beta-estradiol (E2) (1 mg
      orally twice daily) replacement. Serum GH concentrations (n = 280/subject) were
      assayed by chemiluminescence. The resultant GH time series was evaluated by
      deconvolution analysis, the approximate entropy statistic, and cosine regression
      to quantitate pulsatile, entropic (feedback-sensitive), and 24-h rhythmic GH
      release, respectively. Statistical comparisons revealed that E2 repletion
      increased the mean (+/- SEM) serum E2 concentration to 222 +/- 26 pg/ml from 16
      +/- 1.7 pg/ml during placebo (P < 0.001) and suppressed the serum LH by 48% (P =
      0.0033), serum FSH by 64% (P < 0.001), and serum IGF-I by 44% (P = 0.021). Double
      peptidyl secretagogue stimulation elevated mean 24-h serum GH concentrations to
      8.1 +/- 1.0 microg/liter (placebo) and 7.7 +/- 0.89 microg/liter (E2; P = NS) and
      evoked prominently pulsatile patterns of GH secretion. No primary measure of
      pulsatile or basal GH release was altered by the disparate sex steroid milieu,
      i.e. GH secretory burst amplitudes of 0.62 +/- 0.93 (placebo) and 0.72 +/- 0.16
      (E2) microg/liter x min, GH pulse frequencies of 27 +/- 1.8 (placebo) and 23 +/-
      1.9 (E2) events/24 h, GH half-lives of 12 +/- 0.74 (placebo) and 15 +/- 4.5 (E2)
      min, and basal (nonpulsatile) GH secretion 70 +/- 22 (placebo) and 57 +/- 18 (E2)
      ng/liter x min. The approximate entropy (ApEn) of serial GH release [1.297 +/-
      0.061 (placebo) and 1.323 +/- 0.06 (E2)] and the mesor (cosine mean), amplitude,
      and acrophase (time of the maximum) of 24-h rhythmic GH secretion were likewise
      invariant of estrogen supplementation. Estimated statistical power exceeded 90%
      for detecting significant (P < 0.05) within-subject changes exceeding 30-50% in
      the mean serum GH concentration, GH ApEn, or GH mesor. In contrast, ApEn analysis
      of the evolution of successive GH secretory burst-mass values over 24 h disclosed
      that E2 replacement disrupts the serial regularity of pulsatile GH output
      (elevates the ApEn ratio) during combined GHRH/GHRP-2 stimulation (P = 0.004). In
      summary, short-term elevation of serum E2 concentrations in postmenopausal
      individuals into the midfollicular phase range observed in young women does not
      significantly alter 24-h basal, pulsatile, entropic, or nyctohemeral GH secretion
      monitored under continuous combined drive by GHRH and GHRP-2. As E2 repletion
      without enforced GHRH/GHRP-2 stimulation augments each of the foregoing regulated
      facets of GH release, we infer that one or both of the infused peptidyl
      secretagogues may itself participate in E2's short-term amplification of GH
      secretion in postmenopausal individuals. Estrogen's disruption of the orderliness
      of sequential GH pulse-mass values during fixed GHRH/GHRP-2 feedforward would be
      consistent with a subtle reduction in the release and/or actions of hypothalamic
      somatostatin or an (unexpected) direct pituitary action of the sex steroid.
      Whether comparable dynamics mediate the effects of endogenous estrogen on the GH
      axis in premenopausal women or pubertal girls is not known.

PMID- 11836332
TI  - Increased fasting plasma acylation-stimulating protein concentrations in
      nephrotic syndrome.
AB  - Acylation-stimulating protein (ASP) is an adipocyte-derived protein that has
      recently been suggested to play an important role in the regulation of
      lipoprotein metabolism and triglyceride (TG) storage. ASP also appears to have a
      role in the regulation of energy balance. In addition to its role as a hormonal
      regulator of body weight and energy expenditure, leptin is now implicated as a
      regulatory molecule in lipid metabolism. However, little is known about the
      alterations in fasting plasma ASP and leptin concentrations in the nephrotic
      syndrome. As hyperlipidemia is one of the most striking manifestations of the
      nephrotic syndrome, we have investigated fasting plasma ASP and leptin levels and
      their relation to lipid levels in this syndrome. Twenty-five patients with
      untreated nephrotic syndrome and 25 age-, sex-, and body mass index-matched
      healthy controls were included in the study. Fasting plasma lipoproteins, TG,
      total cholesterol, lipoprotein(a), apolipoprotein AI (apoAI), apoB, urinary
      protein, plasma albumin, third component of complement (C3), ASP, and leptin
      levels were measured in both groups. Total cholesterol, TG, low and very low
      density lipoproteins, lipoprotein(a), apoB, and urinary protein levels were
      increased in the patient group, whereas plasma albumin, high density lipoprotein
      cholesterol, and apoAI levels were decreased compared with those in the control
      group (P < 0.001). Plasma ASP levels were significantly higher in the patient
      group compared with the control subjects (133.72 +/- 65.14 vs. 29.93 +/- 12.68
      nmol/liter; P < 0.001), whereas leptin (2.69 +/- 2.06 vs. 3.99 +/- 2.99 ng/ml; P
      = 0.118) and C3 (1.01 +/- 0.25 vs. 1.06 +/- 0.23 g/liter; P = 0.662) levels were
      not significantly different between the two groups. Plasma leptin levels were
      correlated with body mass index in both nephrotic patients (r(s) = 0.86; P <
      0.001) and controls (r(s) = 0.98; P < 0.001), but were not correlated with the
      other parameters. Fasting ASP concentrations showed no correlation with body mass
      index, proteinuria, plasma albumin, leptin, or any lipid parameter in either
      group, but C3 levels (in patient group: r(s) = 0.92; P < 0.001; in control group:
      r(s) = 0.68; P < 0.001). Our findings showed that plasma ASP levels were
      significantly elevated, whereas leptin levels were normal in the nephrotic
      syndrome. Increased ASP levels in the setting of dyslipidemia in the nephrotic
      syndrome raise the possibility of an ASP receptor defect in adipocytes, which
      also suggests the existence of so-called ASP resistance. Moreover, it is possible
      that ASP activity is maximal, but cannot keep up with increased rates of lipid
      production by the liver. Thus, further studies are needed to elucidate the
      mechanism or source (adipocytes, the liver, or both) of elevated ASP
      concentrations in the nephrotic syndrome.

PMID- 11836334
TI  - Mutation screening of the urocortin gene: identification of new single nucleotide
      polymorphisms and association studies with obesity in French Caucasians.
AB  - A linkage between obesity-related phenotypes and the 2p21-23 locus has been
      reported previously. The urocortin (UCN) gene resides at this interval, and its
      protein decreases appetite behavior, suggesting that UCN may be a candidate gene
      for susceptibility to obesity. We localized the UCN gene by radiation hybrid
      mapping, and the surrounding markers were genotyped in a collection of French
      families. Evidence for linkage was shown between the marker D2S165 and leptin
      levels (LOD score, 1.34; P = 0.006) and between D2S2247 and the z-score of body
      mass index (LOD score, 1.829; P = 0.0019). The gene was screened for SNPs in 96
      obese patients. Four new variants were established. Two single nucleotide
      polymorphisms were located in the promoter (-535 A-->G, -286 G-->A), one in
      intron 1 (+31 C-->G), and one in the 3'-untranslated region (+34 C-->T).
      Association studies in cohorts of 722 unrelated obese and 381 control subjects
      and transmission disequilibrium tests, performed for the two frequent promoter
      polymorphisms, in 120 families (894 individuals) showed that no association was
      present between these variants and obesity, obesity-related phenotypes, and
      diabetes. Thus, our analyses of the genetic variations of the UCN gene suggest
      that, at least in French Caucasians, they do not represent a major cause of
      obesity.

PMID- 11836335
TI  - Effects of aging on vasopressin production in a kindred with autosomal dominant
      neurohypophyseal diabetes insipidus due to the DeltaE47 neurophysin mutation.
AB  - Postmortem examinations of the hypothalamus of patients with autosomal dominant
      neurohypophyseal diabetes insipidus (adNDI), which have been reported only on
      persons dying between the ages of 37-87 yr, reveal the presence of the arginine
      vasopressin (AVP)-producing parvocellular neurons but the absence of 95% of the
      expected AVP-producing magnocellular neurons. To determine whether the clinical
      course of adNDI is compatible with the hypothesis that the neuropathologic
      findings are attributable to a progressive loss of magnocellular neurons
      beginning in early life, we performed posterior pituitary magnetic resonance
      imaging and water deprivation tests, including plasma ACTH measurements, on 17
      affected members of a kindred with the deltaE47 neurophysin mutation whose ages
      ranged from 3 months to 54 yr. Nine adult nonaffected members (ages, 20-56 yr)
      underwent these tests as controls. All six children undergoing magnetic resonance
      imaging demonstrated a posterior pituitary hyperintense signal (PPHS). Eight of
      nine affected adults showed an absent or barely visible PPHS, whereas eight of
      nine age-matched nonaffected adults produced a normal size PPHS. During water
      deprivation tests, infants concentrated their urine normally, and a 3-month-old
      infant produced a high plasma AVP level of 15.7 pmol/liter. By school age,
      affected children were no longer able to concentrate their urine or prevent
      hypernatremia. Affected adults became dehydrated; their median plasma AVP level
      was less than 1.0 pmol/liter, but their median fasting plasma ACTH was 2-fold
      greater than the level of nonaffected adults (10.0 vs. 5.0 pmol/liter; P =
      0.008). These results suggest that adNDI is a progressive disease associated with
      chronic loss of the magnocellular neurons that supply AVP to the posterior
      pituitary but preservation of the parvocellular neurons that supply AVP and CRH
      to the median eminence and stimulate ACTH production during hypernatremia.

PMID- 11836336
TI  - 11beta-hydroxysteroid dehydrogenase type 2 is expressed in the human kidney
      glomerulus.
AB  - Our previous study demonstrated that the GR is expressed in the human kidney
      glomerulus. The function of the GR of glomerular cells might be affected by the
      concentration of intracellular glucocorticoids, which is modulated by 11beta
      hydroxysteroid dehydrogenase type 2 (11betaHSD2). Because the expression of
      11betaHSD2 in the glomerular cells remains unclear, we used competitive RT-PCR
      and immunoblotting to detect the expression of 11betaHSD2 mRNA and protein in
      isolated human glomeruli, in whole kidney cortex as a positive control, and in a
      human glomerular visceral epithelial cell line. 11betaHSD2 mRNA was detected in
      all samples. Specific antihuman 11betaHSD2 antibody recognized a single band at
      41 kDa, consistent with the molecular mass of human 11betaHSD2, in the samples of
      the isolated glomeruli and whole kidney cortex. Furthermore, definite 11betaHSD2
      enzymatic activity was also determined with the sample of isolated glomeruli. We
      also performed immunohistochemistry by light and electron microscopy to determine
      the cellular and subcellular localization of 11betaHSD2 in the human glomeruli.
      Immunoreactivity of the enzyme was clearly observed in the glomerular visceral
      epithelial cells and endothelial cells as well as in the distal convoluted
      tubules and collecting ducts. The subcellular localization of 11betaHSD2 was
      shown to be endoplasmic reticulum. These results suggest that 11betaHSD2 might
      play a crucial role in modulating the intracellular concentration of
      glucocorticoids in human glomerular cells.

PMID- 11836337
TI  - Macrophage migration inhibitory factor is markedly expressed in active and early
      stage endometriotic lesions.
AB  - The establishment of a new vascular supply is essential for the survival of
      endometrial tissue and its development in ectopic locations. We have previously
      shown that ectopic endometrial cells release an important mitogenic activity for
      human endothelial cells and identified macrophage migration inhibitory factor
      (MIF) as one of the principal bioactive molecules involved in endothelial cell
      proliferation. In the present study, immunohistochemical and dual
      immunofluorescence analyses showed that MIF is effectively expressed by
      endometriotic tissue, particularly in the glands, and identified endothelial
      cells, macrophages, and T lymphocytes as cells markedly expressing MIF in the
      stroma. Western blot analysis showed a single 12.5-kDa band corresponding to the
      known mol wt of the molecule. The highest concentrations of MIF protein in
      endometriotic tissue, as measured by ELISA, were found in flame-like red
      endometriotic lesions, compared with typical black-bluish (P < 0.01) or with
      white lesions (P < 0.01). Interestingly, MIF displayed a marked expression in
      lesions from the initial stage of endometriosis (stage I). Semiquantitative RT
      PCR analysis of MIF mRNA levels in the same endometriotic tissues showed a
      pattern of expression comparable with that of the protein. In view of its potent
      proinflammatory and angiogenic properties, local production of MIF within
      endometrial implants, particularly in those that are highly vascularized and
      representing the earliest and most active forms of the disease, make plausible
      the involvement of this factor in the local immunoinflammatory process observed
      in endometriosis and the initial steps of endometriotic tissue growth and
      development.

PMID- 11836338
TI  - Neurotropins and their receptors are expressed in the human fetal ovary.
AB  - Mammalian ovarian development is characterized by a sequential pattern of mitotic
      proliferation of oogonia, initiation then arrest of meiosis, and primordial
      follicle formation. The factors regulating these processes are poorly understood.
      The neurotropins are survival and differentiation factors in the nervous system,
      acting via high affinity receptors of the trk protooncogene family and the low
      affinity p75 nerve growth factor receptor, and have also been described in the
      rodent ovary, where changes in NT4/TrkB gene expression have been detected at the
      time of primordial follicle formation. There are no data on neurotropin
      expression in the normal human ovary. We have investigated the expression and
      localization of neurotropins and their receptors in the midtrimester human fetal
      ovary (13-21 wk gestation). Expression of mRNA for neurotropins and their
      receptors was detected by RT-PCR. Clusters of oogonia were found to be the
      predominant site of NT4 mRNA expression using in situ hybridization. However, at
      later gestations granulosa cells of primordial follicles showed increased
      expression, with lesser expression in the enclosed oocytes. NT4 protein was also
      localized to the granulosa cells by immunohistochemistry and at earlier
      developmental stages to epithelioid cells, which were mingled with clusters of
      oogonia not expressing NT4. TrkB receptor protein was localized by
      immunohistochemistry to germ cells at all gestations examined. The p75 nerve
      growth factor receptor protein was exclusively expressed in the ovarian stroma.
      These data demonstrate the expression of neurotropins and their receptors within
      the human fetal ovary. Developmental changes in the pattern of expression of NT4
      around the time of primordial follicle formation suggest that neurotropins may be
      involved in signaling between somatic cells and germ cells at this crucial stage
      of ovarian development.

PMID- 11836339
TI  - Combined 17alpha-Hydroxylase/17,20-lyase deficiency caused by Phe93Cys mutation
      in the CYP17 gene.
AB  - Seventeen alpha-hydroxylase/17,20-lyase deficiency is a rare, autosomal recessive
      form of congenital adrenal hyperplasia not linked to human leukocyte antigen and
      characterized by the coexistence of hypertension caused by the hyperproduction of
      mineralocorticoid precursors and sexual abnormalities, such as male
      pseudohermaphroditism and sexual infantilism in female, due to impaired
      production of sex hormones. Both 17alpha-hydroxylase and 17,20-lyase reactions
      are catalyzed by a single polypeptide, cytochrome P450c17 (CYP17), which is
      encoded by the CYP17 gene located on chromosome 10q24-q25. Mutations in the CYP17
      gene have been recognized to cause the 17alpha-hydroxylase/17,20-lyase deficiency
      syndrome. Here, we describe two phenotypically and hormonally affected Italian
      patients with 17alpha-hydroxylase/17,20-lyase deficiency. The family history
      revealed consanguinity of the parents. Linkage and haplotype analyses using
      microsatellites on chromosome 10q24-q25 demonstrated that the two affected
      individuals were homozygous at these loci. The mutation screening of the CYP17
      gene identified a new Phe93Cys missense mutation in exon 1. The amino acid
      substitution is located in a highly conserved region of the protein and is not a
      polymorphism because it is not present in one hundred normal alleles. In vitro
      functional studies showed that the Phe93Cys mutated CYP17 retains only 10% of
      both 17alphahydroxylase and 17,20-lyase activities, according to the severe
      phenotype. Our results shed more light on the structure-function relationship of
      the CYP17 protein indicating that Phe 93 is crucial for both enzymatic
      activities.

PMID- 11836340
TI  - TR expression and function in human bone marrow stromal and osteoblast-like
      cells.
AB  - Thyroid hormones influence both bone formation and bone resorption. In vitro
      studies demonstrate direct effects of thyroid hormones on cells of the osteoblast
      lineage. Transcriptional regulation by thyroid hormones is mediated by ligand
      dependent transcription factors called TRs. The three main T(3)-binding TR
      isoforms are TRalpha1, TRbeta1, and TRbeta2. TRs have been identified in cells of
      the osteoblast lineage, but it is still not known whether TR isoform expression
      differs in primary cultures of human osteoblasts. We used immunocytochemistry,
      Western blotting, nuclear binding assays, and transient transfection studies to
      examine the expression of functional TR isoforms in primary cultures of
      osteoblasts (hOb) derived from explants of trabecular bone, in human bone marrow
      stromal cells (hBMS), which are believed to be the source of osteoblast
      progenitor cells, and for comparison in the transformed human osteosarcoma cell
      lines MG63 and SaOs-2. TRalpha1, TRbeta1, and TRbeta2 proteins were expressed in
      all cells, although expression was greatest in MG63 > hBMS > SaOs-2 > hOb.
      Differences between isoforms were also apparent, with TRalpha1> TRbeta1 > TRbeta2
      in all cell types. Incubation with [(125)I]T(3) confirmed reversible T(3) binding
      to cell nuclei. Specific binding was greatest in MG63 > hBMS > SaOs-2 > hOb.
      Finally, endogenous TR activity was determined in transfections using a thyroid
      hormone response element derived from the rat GH gene linked to the luciferase
      reporter gene. In MG63 and hBMS cells T(3) treatment increased luciferase
      activity 5.5 +/- 0.7-fold (P < 0.05), confirming the presence of endogenous
      receptors. In SaOs-2 and hOb cells, T(3) treatment had no effect on thyroid
      hormone response element-thymidine kinase-luciferase expression, suggesting that
      in these cells TR expression was too low to be detected. These results indicate
      that three main TR isoforms are expressed in cells of the human osteoblast
      lineage, but that expression and endogenous TR activity are predominantly present
      in hBMS cells. Whether there are distinct mechanisms of thyroid hormone action
      mediated by TRalpha1, TRbeta1, and TRbeta2 in hOb and hBMS cells remains to be
      shown.

PMID- 11836342
TI  - Autocrine regulation of human prostate carcinoma cell proliferation by
      somatostatin through the modulation of the SH2 domain containing protein tyrosine
      phosphatase (SHP)-1.
AB  - The present study was intended to gain additional information on the growth
      regulation of prostate by somatostatin (SRIF) and the intracellular events
      involved. The human prostate adenocarcinoma cell lines PC-3 and LNCaP produce
      SRIF and express subtypes 2 and 5 of SRIF receptors. The secretion of SRIF is
      related to the proliferative status of these cells; an inverse relationship
      exists between cell proliferation and the amount of secreted SRIF. Moreover, the
      growth of PC-3 cells is inhibited by SRIF overexpression and increased by
      blockage of endogenous SRIF. Coincident with the increase in SRIF secretion, the
      activity and levels of the SH2 domain containing protein tyrosine phosphatase
      (SHP)-1, present in PC-3 cells are augmented, but the effect can be partially
      prevented by neutralization of secreted endogenously SRIF. The activity of SHP-1
      is also stimulated by the SRIF analog RC160. Overexpression of SHP-1 induces
      inhibition of PC-3 cell growth. SHP-1 is also present in normal prostate, benign
      prostatic hyperplasia, prostatic intraepithelial neoplasia, and well
      differentiated adenocarcinoma. In contrast, no signal is detected in poorly
      differentiated prostate cancer. These findings demonstrate that SRIF inhibits PC
      3 and LNCaP cell proliferation through an autocrine/paracrine SRIF loop. This
      effect could be mediated by activation of the tyrosine phosphatase SHP-1 detected
      in these cells as well as in human prostate and prostate cancer.

PMID- 11836343
TI  - Hypothalamic NPY and agouti-related protein are increased in human illness but
      not in Prader-Willi syndrome and other obese subjects.
AB  - Animal studies have demonstrated the importance of orexigenic NPY and agouti
      related protein (AGRP) hypothalamic neurons, which are inhibited by the adipocyte
      hormone leptin, in the regulation of body weight and neuroendocrine secretion. We
      have examined NPY and AGRP neurons in postmortem human hypothalami from controls,
      Prader-Willi syndrome and other obese subjects, using quantitative
      immunocytochemistry (ICC) and in situ hybridization, to identify causes of leptin
      resistance in human obesity. Using combined ICC and in situ hybridization, AGRP,
      but not POMC, was colocalized with NPY in infundibular nucleus neurons.
      Infundibular nucleus (including median eminence) NPY ICC staining or mRNA
      expression, and AGRP ICC staining, increased with premorbid illness duration. NPY
      ICC staining and mRNA expression were reduced in obese subjects, but AGRP ICC
      staining was unchanged, correcting for illness duration. This suggests normal
      responses of NPY and AGRP neurons to peripheral signals, such as leptin and
      insulin, in human illness and obesity. The pathophysiology of obesity and illness
      associated anorexia appear to lie in downstream or separate neuronal circuits,
      but the infundibular neurons may mediate neuroendocrine responses to illness. The
      implications for pharmacological treatment of human obesity are discussed.

PMID- 11836344
TI  - Expression of PDS/Pds, the Pendred syndrome gene, in endometrium.
AB  - Expression of the Pendred syndrome gene (PDS/Pds) is thought to be responsible
      for the iodide transport in the thyroid as well as the formation and function of
      the inner ear. Its mRNA is also expressed in the kidney and placenta. We report
      here that PDS and its encoded protein (pendrin) are also expressed in the
      endometrium. The RNA levels of rat PDS in the endometrium and kidney were much
      higher than those of the thyroid, opposite of the pattern of RNA expression in
      humans. In human endometrium, pendrin localization changed from the basal to
      apical surfaces of the epithelium during progression of the menstrual cycle. This
      suggests a possible role for pendrin in cationic ion transport required to
      maintain the physiological function of the endometrium. Since there is no
      evidence of endometrial abnormalities in patients with Pendred syndrome, it
      suggests the existence of a compensatory mechanisms for pendrin's function in the
      uterus.

PMID- 11836345
TI  - Effects of recombinant human growth hormone on hepatic lipid and carbohydrate
      metabolism in HIV-infected patients with fat accumulation.
AB  - We recently reported that treatment with a pharmacologic dose of recombinant
      human growth hormone (GH) resulted in a significant loss of body fat and gain in
      lean tissue in HIV-infected patients with syndromes of fat accumulation. However,
      insulin-mediated glucose disposal decreased transiently after one month of GH
      therapy. The present paper focuses on the changes of hepatic carbohydrate and fat
      metabolism associated with GH treatment in the same subjects. We assessed hepatic
      insulin sensitivity under both fasting and hyperinsulinemic-euglycemic clamp
      conditions prior to and after one and six months of GH treatment (3 mg/day) in
      five patients using stable isotope tracer techniques. Indirect calorimetry, and
      measurements of lipid concentrations. Fasting endogenous glucose production (EGP)
      increased significantly at one month (12.0 +/- 0.7 to 14.9 +/- 0.9
      micromol/kg/min, P < 0.03), and the increase was sustained at six months of GH
      treatment (14.0 +/- 1.1 micromol/kg/min, NS). This increase in EGP was driven in
      part by increased glucogenesis (GNG) (3.5 +/- 0.9 to 5.2 +/- 0.9 and 5.8 +/-1.2
      micromol/kg/min, n = 4, P < 0.01 and P < 0.01 at one and six months,
      respectively); small changes in hepatic glycogenolysis also contributed.
      Sustained increases in lipolysis and progressive decreases in hepatic fractional
      de novo lipogenesis (DNL) and triglyceride concentrations occurred with GH
      treatment. These changes were accompanied by an improved lipid profile with a
      significant increase in HDL cholesterol and significant decreases in total and
      LDL cholesterol and triglyceride levels, the latter consistent with the decrease
      in hepatic DNL. During a hyperinsulinemic-euglycemic glucose clamp, EGP and GNG
      were markedly suppressed compared to the corresponding time points under fasting
      conditions, albeit less so when measured after one month of GH treatment. Thus,
      in HIV-infected patients with abnormal fat distribution, pharmacologic doses of
      GH improved the overall lipid profile, but worsened glucose homeostasis under
      both fasting and hyperinsulinemic conditions. The combined implications of these
      positive and negative metabolic effects for cardiovascular disease risk remain
      unknown.

PMID- 11836346
TI  - Vitamin D status and redefining serum PTH reference range in the elderly.

PMID- 11836347
TI  - Comment on "thyrotropin receptor expression in cardiac muscle tissue".

PMID- 11836351
TI  - QUICKI is a useful and accurate index of insulin sensitivity.

PMID- 11836348
TI  - Severe embryopathy and exposure to methimazole in early pregnancy.

PMID- 11836352
TI  - QUICKI is not a useful and accurate index of insulin sensitivity following
      exercise training.

PMID- 11836353
TI  - Different presentation of bone mass in mice and humans with congenital leptin
      deficiency.

PMID- 11836356
TI  - Identification of a 52 kb deletion downstream of the SOST gene in patients with
      van Buchem disease.
AB  - Van Buchem disease is an autosomal recessive skeletal dysplasia characterised by
      generalised bone overgrowth, predominantly in the skull and mandible. Clinical
      complications including facial nerve palsy, optic atrophy, and impaired hearing
      occur in most patients. These features are very similar to those of sclerosteosis
      and the two conditions are only differentiated by the hand malformations and the
      tall stature appearing in sclerosteosis. Using an extended Dutch inbred van
      Buchem family and two inbred sclerosteosis families, we mapped both disease genes
      to the same region on chromosome 17q12-q21, supporting the hypothesis that van
      Buchem disease and sclerosteosis are caused by mutations in the same gene. In a
      previous study, we positionally cloned a novel gene, called SOST, from the
      linkage interval and identified three different, homozygous mutations in the SOST
      gene in sclerosteosis patients leading to loss of function of the underlying
      protein. The present study focuses on the identification of a 52 kb deletion in
      all patients from the van Buchem family. The deletion, which results from a
      homologous recombination between Alu sequences, starts approximately 35 kb
      downstream of the SOST gene. Since no evidence was found for the presence of a
      gene within the deleted region, we hypothesise that the presence of the deletion
      leads to a down regulation of the transcription of the SOST gene by a cis
      regulatory action or a position effect.

PMID- 11836355
TI  - Current status of human chromosome 14.
AB  - Over the past three decades, extensive genetic, physical, transcript, and
      sequence maps have assisted in the mapping of over 30 genetic diseases and in the
      identification of over 550 genes on human chromosome 14. Additional genetic
      disorders were assigned to chromosome 14 by studying either constitutional or
      acquired chromosome aberrations of affected subjects. Studies of benign and
      malignant tumours by karyotype analyses and by allelotyping with a panel of
      polymorphic genetic markers have further suggested the presence of several tumour
      suppressor loci on chromosome 14. The search for disease genes on human
      chromosome 14 has also been achieved by exploiting the human-mouse comparative
      maps. Research on uniparental disomy and on the search for imprinted genes has
      supported evidence of epigenetic inheritance as a result of imprinting on human
      chromosome 14. This review focuses on the current developments on human
      chromosome 14 with respect to genetic maps, physical maps, transcript maps,
      sequence maps, genes, diseases, mouse-human comparative maps, and imprinting.

PMID- 11836359
TI  - Corneal dystrophy and perceptive deafness (Harboyan syndrome): CDPD1 maps to
      20p13.
AB  - The association of congenital corneal dystrophy with teenage onset perceptive
      hearing loss (Harboyan syndrome) has been reported in two sibships, one with
      consanguineous parents, which were consistent with autosomal recessive
      transmission. We have observed a Moroccan sibship where four girls and one boy
      were affected with this rare syndrome. The parents were first cousins once
      removed and unaffected. Genome wide homozygosity mapping using 386 microsatellite
      markers linked the locus to 20p13. A maximum multipoint lod score of 4.20 was
      obtained at marker D20S179. The minimal critical region is 7.73 cM between
      markers D20S199 and D20S437. These results confirm the syndromic association of
      congenital corneal dystrophy and teenage onset hearing loss, and further increase
      the genetic heterogeneity of recessive deafness.

PMID- 11836358
TI  - A locus for isolated cataract on human Xp.
AB  - PURPOSE: To genetically map the gene causing isolated X linked cataract in a
      large European pedigree. METHODS: Using the patient registers at Birmingham
      Women's Hospital, UK, we identified and examined 23 members of a four generation
      family with nuclear cataract. Four of six affected males also had complex
      congenital heart disease. Pedigree data were collated and leucocyte DNA extracted
      from venous blood. Linkage analysis by PCR based microsatellite marker genotyping
      was used to identify the disease locus and mutations within candidate genes
      screened by direct sequencing. RESULTS: The disease locus was genetically refined
      to chromosome Xp22, within a 3 cM linkage interval flanked by markers DXS9902 and
      DXS999 (Zmax=3.64 at theta=0 for marker DXS8036). CONCLUSIONS: This is the first
      report of a locus for isolated inherited cataract on the X chromosome. The
      disease interval lies within the Nance-Horan locus suggesting allelic
      heterogeneity. The apparent association with congenital cardiac anomalies
      suggests a possible new oculocardiac syndrome.

PMID- 11836357
TI  - The fibulin-1 gene (FBLN1) is disrupted in a t(12;22) associated with a complex
      type of synpolydactyly.
AB  - Molecular analysis of the reciprocal chromosomal translocation
      t(12;22)(p11.2;q13.3) cosegregating with a complex type of synpolydactyly showed
      involvement of an alternatively spliced exon of the fibulin-1 gene (FBLN1 located
      in 22q13.3) and the C12orf2 (HoJ-1) gene on the short arm of chromosome 12.
      Investigation of the possible functional involvement of the fibulin-1 protein
      (FBLN1) in the observed phenotype showed that FBLN1 is expressed in the
      extracellular matrix (ECM) in association with the digits in the developing limb.
      Furthermore, fibroblasts derived from patients with the complex type of
      synpolydactyly displayed alterations in the level of FBLN1-D splice variant
      incorporated into the ECM and secreted into the conditioned culture medium. By
      contrast, the expression of the FBLN1-C splice variant was not perturbed in the
      patient fibroblasts. Based on these findings, we propose that the t(12;22)
      results in haploinsufficiency of the FBLN1-D variant, which could lead to the
      observed limb malformations.

PMID- 11836360
TI  - Abnormal expression of the KLF8 (ZNF741) gene in a female patient with an
      X;autosome translocation t(X;21)(p11.2;q22.3) and non-syndromic mental
      retardation.
AB  - Non-syndromic X linked mental retardation (MRX) is a heterogeneous group of
      conditions in which all patients have mental retardation as the only constant
      phenotypic feature. We have identified a female patient with mental retardation
      and a balanced translocation involving chromosomes X and 21,
      t(X;21)(p11.2;q22.3). Physical mapping of the translocation breakpoint on the
      human X chromosome was performed using fluorescence in situ hybridisation. We
      have mapped the X chromosome breakpoint to a 21 kb DNA fragment upstream of the
      first exon of the KLF8 (ZNF741) gene in Xp11.21. We have subsequently shown that
      the KLF8 transcript is no longer detected in cells from the patient, although
      KLF8 expression is otherwise normally present in control lymphoblasts. Mutation
      screening of probands from 20 unrelated XLMR families linked to the proximal
      short arm of the human X chromosome failed to show any mutation in the coding
      region of the KLF8 gene.

PMID- 11836361
TI  - A genome wide scan for familial high myopia suggests a novel locus on chromosome
      7q36.

PMID- 11836362
TI  - Supportive evidence for the DYX3 dyslexia susceptibility gene in Canadian
      families.

PMID- 11836363
TI  - Unique de novo mutation of BRCA2 in a woman with early onset breast cancer.

PMID- 11836364
TI  - A variant of osteogenesis imperfecta type IV with resolving kyphomelia is caused
      by a novel COL1A2 mutation.

PMID- 11836365
TI  - Functional characterisation of MeCP2 mutations found in male patients with X
      linked mental retardation.

PMID- 11836366
TI  - Acrofacial dysostosis in a patient with the TSC2-PKD1 contiguous gene syndrome.

PMID- 11836367
TI  - Partial trisomy 9p12p21.3 with a normal phenotype.

PMID- 11836368
TI  - Craniofacial anomalies, cataracts, congenital heart disease, sacral neural tube
      defects, and growth and developmental retardation in two sisters: a new autosomal
      recessive MCA/MR syndrome?

PMID- 11836369
TI  - Dysmorphism, variable overgrowth, normal bone age, and severe developmental
      delay: a "Sotos-like" syndrome?

PMID- 11836370
TI  - Molecular changes in skin predict predisposition to breast cancer.

PMID- 11836371
TI  - Spastic paraparesis and atypical dementia caused by PSEN1 mutation (P264L),
      responsible for Alzheimer's disease.

PMID- 11836372
TI  - Identification and characterisation of mutations underlying Sanfilippo syndrome
      type B (mucopolysaccharidosis type IIIB).

PMID- 11836373
TI  - Severe phenotype in Angelman syndrome resulting from paternal isochromosome 15.

PMID- 11836374
TI  - Inositol and folate resistant neural tube defects.

PMID- 11836375
TI  - Constitutional de novo interstitial deletion of 8 Mb on chromosome 22q12.1-12.3
      encompassing the neurofibromatosis type 2 (NF2) locus in a dysmorphic girl with
      severe malformations.

PMID- 11836376
TI  - Refined mapping of the gene for otopalatodigital syndrome type I.

PMID- 11836377
TI  - A case of Costello syndrome and glycogen storage disease type III.

PMID- 11836378
TI  - A patient with a supernumerary marker chromosome (15), Angelman syndrome, and
      uniparental disomy resulting from paternal meiosis II non-disjunction.

PMID- 11836379
TI  - Exclusion of PTEN, CTNNB1, and PTCH as candidate genes for Birt-Hogg-Dube
      syndrome.

PMID- 11836380
TI  - The herpes simplex virus type 1 U(S)11 protein interacts with protein kinase R in
      infected cells and requires a 30-amino-acid sequence adjacent to a kinase
      substrate domain.
AB  - The herpes simplex virus type 1 gamma(1)34.5 gene product precludes the host
      mediated protein shutoff response induced by activated protein kinase R (PKR).
      Earlier studies demonstrated that recombinant viruses lacking the gamma(1)34.5
      gene (Deltagamma(1)34.5) developed secondary mutations that allowed earlier
      U(S)11 expression and enabled continued protein synthesis. Further, in vitro
      studies demonstrated that a recombinant expressed U(S)11 protein binds PKR,
      blocks the phosphorylation of the alpha subunit of eukaryotic initiation factor 2
      (eIF-2alpha) by activated PKR, and, if provided prior to PKR activation,
      precluded PKR autophosphorylation. The present study furthers the hypothesis that
      early U(S)11 production precludes PKR-mediated host protein shutoff by
      demonstrating that (i) U(S)11 and PKR interact in the context of viral infection,
      (ii) this interaction is RNA dependent and requires a 30-amino-acid domain (amino
      acids 91 to 121) in the carboxyl domain of the U(S)11 protein, (iii) the proteins
      biochemically colocalize in the S100 ribosomal fraction, and (iv) there is a PKR
      substrate domain immediately adjacent to the binding domain. The results suggest
      that the U(S)11 interaction with PKR at the ribosome is RNA dependent and that
      the U(S)11 protein contains a substrate domain with homology to eIF-2alpha in
      close proximity to an essential binding domain.

PMID- 11836381
TI  - Recruitment of the Crm1 nuclear export factor is sufficient to induce cytoplasmic
      expression of incompletely spliced human immunodeficiency virus mRNAs.
AB  - Cytoplasmic expression of the incompletely spliced RNA transcripts that encode
      the late, structural proteins of human immunodeficiency virus type 1 (HIV-1) is
      dependent on the viral Rev regulatory protein. General agreement exists that Rev
      acts, at least in part, by recruiting the cellular Crm1 nuclear export factor to
      HIV-1 transcripts bearing the Rev response element RNA target, and thereby
      inducing their nuclear egress. However, several groups have argued that Crm1
      recruitment may not be sufficient for Rev function. Thus, several additional
      candidate cofactors for Rev have been proposed, and Rev has also been suggested
      to also inhibit the nuclear splicing of HIV-1 transcripts and/or to directly
      enhance their cytoplasmic translation. To examine whether Crm1 recruitment is,
      instead, sufficient to activate the nuclear export of viral mRNAs, we targeted a
      leucine-rich Crm1 binding domain, derived from a heterologous protein that
      normally plays no role in RNA metabolism, to HIV-1 RNAs and showed that this
      tethered Crm1 binding domain is sufficient to induce the nuclear export and
      cytoplasmic translation of late HIV-1 mRNA species. More importantly, we show
      that direct tethering of the Crm1 nuclear export factor to target mRNAs, by
      fusion to a heterologous RNA binding domain, is in and of itself sufficient to
      induce the nuclear export and cytoplasmic expression of the unspliced HIV-1 mRNAs
      that encode the viral Gag proteins.

PMID- 11836382
TI  - Ubiquitination of both adeno-associated virus type 2 and 5 capsid proteins
      affects the transduction efficiency of recombinant vectors.
AB  - In the presence of complementing adeno-associated virus type 2 (AAV-2) Rep
      proteins, AAV-2 genomes can be pseudotyped with the AAV-5 capsid to assemble
      infectious virions. Using this pseudotyping strategy, the involvement of the
      ubiquitin-proteasome system in AAV-5 and AAV-2 capsid-mediated infections was
      compared. A recombinant AAV-2 (rAAV-2) proviral luciferase construct was packaged
      into both AAV-2 and AAV-5 capsid particles, and transduction efficiencies in a
      number of cell lines were compared. Using luciferase expression as the end point,
      we demonstrated that coadministration of the viruses with proteasome inhibitors
      not only increased the transduction efficiency of rAAV-2, as previously reported,
      but also augmented rAAV-5-mediated gene transfer. Increased transgene expression
      was independent of viral genome stability, since there was no significant
      difference in the amounts of internalized viral DNA in the presence or absence of
      proteasome inhibitors. Western blot assays of immunoprecipitated viral capsid
      proteins from infected HeLa cell lysates and in vitro reconstitution experiments
      revealed evidence for ubiquitin conjugation of both AAV-2 and AAV-5 capsids.
      Interestingly, heat-denatured virus particles were preferential substrates for in
      vitro ubiquitination, suggesting that endosomal processing of the viral capsid
      proteins is a prelude to ubiquitination. Furthermore, ubiquitination may be a
      signal for processing of the capsid at the time of virion disassembly. These
      studies suggest that the previously reported influences of the ubiquitin
      proteasome system on rAAV-2 transduction are also active for rAAV-5 and provide a
      clearer mechanistic framework for understanding the functional significance of
      ubiquitination.

PMID- 11836383
TI  - Pathogenesis of herpes simplex virus type 2 virion host shutoff (vhs) mutants.
AB  - During lytic infection, the virion host shutoff (vhs) protein mediates the rapid
      degradation of mRNA and the shutoff of host protein synthesis. In vivo, herpes
      simplex virus type 1 (HSV-1) mutants lacking vhs activity are profoundly
      attenuated. Homologs of vhs exist in all of the neurotropic herpesviruses, and
      the goal of this study was to determine the virulence of HSV-2 mutants lacking
      vhs. Two HSV-2 recombinants were used in this study: 333-vhsB, which has a lacZ
      cassette inserted into the N terminus of vhs, and 333d41, which has a 939-bp
      deletion in vhs. As expected, both 333-vhsB and 333d41 failed to induce the
      cellular RNA degradation characteristic of HSV. Corneal, vaginal, and
      intracerebral routes of infection were used to study pathogenesis. Both viruses
      grew to significantly lower titers in the corneas, trigeminal ganglia, vaginas,
      dorsal root ganglia, spinal cords, and brains of mice than wild-type and rescue
      viruses, with a correspondingly reduced induction of disease. Both viruses,
      however, reactivated efficiently from explanted trigeminal ganglia, showing that
      vhs is dispensable for reactivation. The lethality of 333d41 following peripheral
      infection of mice, however, was significantly higher than that of 333-vhsB,
      suggesting that some of the attenuation of 333-vhsB may be due to the presence of
      a lacZ cassette in the vhs locus. Taken together, these data show that vhs
      represents an important determinant of HSV-2 pathogenesis and have implications
      for the design of HSV-2 recombinants and vaccines.

PMID- 11836384
TI  - Efficient cleavage of ribosome-associated poly(A)-binding protein by enterovirus
      3C protease.
AB  - Poliovirus (PV) causes a rapid and drastic inhibition of host cell cap-dependent
      protein synthesis during infection while preferentially allowing cap-independent
      translation of its own genomic RNA via an internal ribosome entry site element.
      Inhibition of cap-dependent translation is partly mediated by cleavage of an
      essential translation initiation factor, eIF4GI, during PV infection. In addition
      to cleavage of eIF4GI, cleavage of eIF4GII and poly(A)-binding protein (PABP) has
      been recently proposed to contribute to complete host translation shutoff;
      however, the relative importance of eIF4GII and PABP cleavage has not been
      determined. At times when cap-dependent translation is first blocked during
      infection, only 25 to 35% of the total cellular PABP is cleaved; therefore, we
      hypothesized that the pool of PABP associated with polysomes may be
      preferentially targeted by viral proteases. We have investigated what cleavage
      products of PABP are produced in vivo and the substrate determinants for cleavage
      of PABP by 2A protease (2A(pro)) or 3C protease (3C(pro)). Our results show that
      PABP in ribosome-enriched fractions is preferentially cleaved in vitro and in
      vivo compared to PABP in other fractions. Furthermore, we have identified four N
      terminal PABP cleavage products produced during PV infection and have shown that
      viral 3C protease generates three of the four cleavage products. Also, 3C(pro) is
      more efficient in cleaving PABP in ribosome-enriched fractions than 2A(pro) in
      vitro. In addition, binding of PABP to poly(A) RNA stimulates 3C(pro)-mediated
      cleavage and inhibits 2A(pro)-mediated cleavage. These results suggest that
      3C(pro) plays a major role in processing PABP during virus infection and that the
      interaction of PABP with translation initiation factors, ribosomes, or poly(A)
      RNA may promote its cleavage by viral 2A and 3C proteases.

PMID- 11836385
TI  - A replication-competent, neutralization-sensitive variant of simian
      immunodeficiency virus lacking 100 amino acids of envelope.
AB  - Coding sequences for the first two variable loops of the gp120 envelope
      glycoprotein were removed from simian immunodeficiency virus (SIV) strain 239
      (SIVmac239). This deletion encompassed 100 amino acids. The resulting virus
      replicated poorly after transfection into immortalized T-cell lines, with peak
      replication occurring only after 25 to 30 days. Limited passaging of
      SIVmac239DeltaV1V2 in cultures gave rise to a variant which had significantly
      improved replication kinetics but which retained the original 100-amino-acid
      deletion in gp120. Cloning and sequencing revealed 11 changes in the envelope,
      including amino acid substitutions in both gp120 (5 substitutions) and gp41(6
      substitutions). Four of the five changes in gp120 are predicted to lie within and
      around the putative coreceptor binding domain, a region which is believed to be
      covered by the V1 and V2 loops in the native envelope complex. Analysis of
      recombinant clones surprisingly revealed that the changes in gp41 were sufficient
      to overcome the replication deficiency created by deletion of the V1 and V2 loops
      from gp120. The SIVmac239DeltaV1V2 envelope displayed a significant reduction in
      its ability to mediate cell-cell fusion, and the infectious titer of
      SIVmac239DeltaV1V2 was approximately four- to eightfold lower than that of
      parental SIVmac239. Although SIVmac239 is strongly dependent on both CD4 and a
      coreceptor for entry, envelope protein lacking the V1 and V2 loops was able to
      mediate fusion with CD4(-) CCR5(+) cells at 60% the level observed with CD4(+)
      CCR5(+) cells. Plasma from SIVmac239-infected monkeys was at least 100 to 1,000
      times more effective at neutralizing SIVmac239DeltaV1V2 than SIVmac239. These
      results demonstrate the dispensability of the V1-V2 sequences of SIVmac239 for
      viral replication, a role for V1 and V2 in shielding the coreceptor binding
      region of the envelope, and the extreme sensitivity of a SIV lacking these
      sequences to antibody-mediated neutralization.

PMID- 11836386
TI  - Selection for c-myc integration sites in polyclonal T-cell lymphomas.
AB  - Type B leukemogenic virus (TBLV) is highly related to mouse mammary tumor virus
      but induces rapidly appearing T-cell lymphomas in mice. Unlike other T-cell
      tumors induced by retroviruses, only 5 to 10% of TBLV-induced lymphomas have
      detectable viral integrations near c-myc by Southern blotting, whereas Northern
      blotting has shown that most tumors have two- to sixfold overexpression of c-myc
      RNA. In this report, PCR was used to demonstrate that at least 30% of these
      lymphomas have TBLV insertions near c-myc. Some tumors contained multiple TBLV
      proviruses in different locations and orientations, suggesting that the tumors
      are polyclonal. The integrated proviruses near c-myc had different numbers (two
      to four) of long terminal repeat (LTR) enhancer repeats, although LTRs with three
      repeat enhancers dominated the proviral population. Passage of polyclonal tumors
      in immunocompetent mice and semiquantitative PCR revealed that only cells with
      particular integrations were selected for growth. In three of six tumors tested,
      proviruses containing four-repeat enhancers near c-myc were selected during tumor
      passage. Since tumor cell selection may be accomplished by overexpression of c
      myc RNA due to proximity to the unique TBLV LTR enhancer, we inserted LTRs at
      various locations within a plasmid containing the entire c-myc locus and cellular
      flanking sequences. To quantitatively measure effects on transcription, the
      Renilla luciferase gene was substituted for most of c-myc exon 2, and transient
      transfections were performed with c-myc reporter constructs in two different T
      cell lines. As expected, insertion of a TBLV LTR with three-repeat enhancers in
      either orientation, 5" and 3", of the myc gene elevated reporter activity from 2-
      to 160-fold, consistent with enhancer function, but four-repeat LTRs had lower
      levels of expression compared to three-repeat LTRs. Surprisingly, LTR insertions
      that gave maximal c-myc expression in transient-transfection assays declined in
      tumor cells selected for growth in vivo. Selection for clonal growth may occur in
      tumor cells that have modest c-myc overexpression after proviral insertion to
      prevent apoptosis.

PMID- 11836387
TI  - Strong CD8 T-cell responses following coimmunization with plasmids expressing the
      dominant pp89 and subdominant M84 antigens of murine cytomegalovirus correlate
      with long-term protection against subsequent viral challenge.
AB  - We previously showed that intradermal immunization with plasmids expressing the
      murine cytomegalovirus (MCMV) protein IE1-pp89 or M84 protects against viral
      challenge and that coimmunization has a synergistic protective effect (C. S.
      Morello, L. D. Cranmer, and D. H. Spector, J. Virol. 74:3696-3708, 2000). Using
      an intracellular gamma interferon cytokine staining assay, we have now
      characterized the CD8+ T-cell response after DNA immunization with pp89, M84, or
      pp89 plus M84. The pp89- and M84-specific CD8+ T-cell responses peaked rapidly
      after three immunizations. DNA immunization and MCMV infection generated similar
      levels of pp89-specific CD8+ T cells. In contrast, a significantly higher level
      of M84-specific CD8+ T cells was elicited by DNA immunization than by MCMV
      infection. Fusion of ubiquitin to pp89 enhanced the CD8+ T-cell response only
      under conditions where vaccination was suboptimal. Three immunizations with
      either pp89, M84, or pp89 plus M84 DNA also provided significant protection
      against MCMV infection for at least 6 months, with the best protection produced
      by coimmunization. A substantial percentage of antigen-specific CD8+ T cells
      remained detectable, and they responded rapidly to the MCMV challenge. These
      results underscore the importance of considering antigens that do not appear to
      be highly immunogenic during infection as DNA vaccine candidates.

PMID- 11836388
TI  - Interaction of translation initiation factor eIF4B with the poliovirus internal
      ribosome entry site.
AB  - Poliovirus translation is initiated at the internal ribosome entry site (IRES).
      Most likely involving the action of standard initiation factors, this highly
      structured cis element in the 5" noncoding region of the viral RNA guides the
      ribosome to an internal silent AUG. The actual start codon for viral protein
      synthesis further downstream is then reached by ribosomal scanning. In this study
      we show that two of the secondary structure elements of the poliovirus IRES,
      domain V and, to a minor extent, domain VI, are the determinants for binding of
      the eukaryotic initiation factor eIF4B. Several mutations in domain V which are
      known to greatly affect poliovirus growth also seriously impair the binding of
      eIF4B. The interaction of eIF4B with the IRES is not dependent on the presence of
      the polypyrimidine tract-binding protein, which also binds to the poliovirus
      IRES. In contrast to its weak interaction with cellular mRNAs, eIF4B remains
      tightly associated with the poliovirus IRES during the formation of complete 80S
      ribosomes. Binding of eIF4B to the IRES is energy dependent, and binding of the
      small ribosomal subunit to the IRES requires the previous energy-dependent
      association of initiation factors with the IRES. These results indicate that the
      interaction of eIF4B with the 3" region of the poliovirus IRES may be directly
      involved in translation initiation.

PMID- 11836389
TI  - Determination of a statistically valid neutralization titer in plasma that
      confers protection against simian-human immunodeficiency virus challenge
      following passive transfer of high-titered neutralizing antibodies.
AB  - We previously reported that high-titered neutralizing antibodies directed against
      the human immunodeficiency virus type 1 (HIV-1) envelope can block the
      establishment of a simian immunodeficiency virus (SIV)/HIV chimeric virus (SHIV)
      infection in two monkeys following passive transfer (R. Shibata et al., Nat. Med.
      5:204-210, 1999). In the present study, increasing amounts of neutralizing
      immunoglobulin G (IgG) were administered to 15 pig-tailed macaques in order to
      obtain a statistically valid protective neutralization endpoint titer in plasma.
      Using an in vitro assay which measures complete neutralization of the challenge
      SHIV, we correlated the titers of neutralizing antibodies in plasma at the time
      of virus inoculation (which ranged from 1:3 to 1:123) with the establishment of
      infection in virus-challenged animals. Ten of 15 monkeys in the present
      experiment were virus free as a result of neutralizing IgG administration as
      monitored by DNA PCR (peripheral blood mononuclear cells and lymph node cells),
      RNA PCR (plasma), virus isolation, and the transfer of lymph node cell
      suspensions (10(8) cells) plus 8 ml of whole blood from protected animals to
      naive macaques. The titer of neutralizing antibodies in the plasma calculated to
      protect 99% of virus-challenged monkeys was 1:38.

PMID- 11836390
TI  - The S4 genome segment of baboon reovirus is bicistronic and encodes a novel
      fusion-associated small transmembrane protein.
AB  - We demonstrate that the S4 genome segment of baboon reovirus (BRV) contains two
      sequential partially overlapping open reading frames (ORFs), both of which are
      functional in vitro and in virus-infected cells. The 15-kDa gene product (p15) of
      the 5"-proximal ORF induces efficient cell-cell fusion when expressed by itself
      in transfected cells, suggesting that p15 is the only viral protein required for
      induction of syncytium formation by BRV. The p15 protein is a small, hydrophobic,
      basic, integral membrane protein, properties shared with the p10 fusion
      associated small transmembrane (FAST) proteins encoded by avian reovirus and
      Nelson Bay reovirus. As with p10, the BRV p15 protein is also a nonstructural
      protein and, therefore, is not involved in virus entry. Sequence analysis
      indicates that p15 shares no significant sequence similarity with the p10 FAST
      proteins and contains a unique repertoire and arrangement of sequence-predicted
      structural and functional motifs. These motifs include a functional N-terminal
      myristylation consensus sequence, an N-proximal proline-rich motif, two potential
      transmembrane domains, and an intervening polybasic region. The unique structural
      properties of p15 suggest that this protein is a novel member of the new family
      of FAST proteins.

PMID- 11836391
TI  - Mechanism of cell entry and transformation by enzootic nasal tumor virus.
AB  - Enzootic nasal tumor virus (ENTV) induces nasal epithelial cancer in infected
      sheep, but it is a simple retrovirus lacking a known oncogene. ENTV is closely
      related to jaagsiekte sheep retrovirus (JSRV), which also causes cancer in sheep
      but in the epithelial cells of the lower airways and alveoli. Here we show that
      as with JSRV, the envelope (Env) protein of ENTV can transform cultured cells and
      thus is likely to be responsible for oncogenesis in animals. In addition, the
      ENTV Env protein mediates virus entry using the same receptor as does JSRV Env,
      the candidate tumor suppressor Hyal2. However, ENTV Env mediates entry into cells
      from a more restricted range of species than does JSRV, and based on this finding
      we have identified amino acid regions in the Env proteins that are important for
      virus entry. Also, because ENTV does not efficiently use human Hyal2 as a
      receptor, we cloned the ovine Hyal2 cDNA and show that the encoded protein
      functions as an efficient receptor for both ENTV and JSRV. In summary, although
      ENTV and JSRV use the same cell surface receptor for cell entry and apparently
      transform cells by the same mechanism, they induce cancer in different tissues of
      infected sheep, indicating that oncogenesis is regulated at some other level. The
      transcriptional regulatory elements in these viruses are quite different,
      indicating that tissue-specific oncogenesis is likely regulated at the level of
      viral gene expression.

PMID- 11836392
TI  - Complement-mediated enhancement of antibody function for neutralization of
      pseudotype virus containing hepatitis C virus E2 chimeric glycoprotein.
AB  - We previously reported a number of features of hepatitis C virus (HCV) chimeric
      glycoproteins related to pseudotype virus entry into mammalian cells. In this
      study, pseudotype virus was neutralized by HCV E2 glycoprotein-specific
      antibodies and infected human sera. Neutralization (50% reduction of pseudotype
      virus plaque formation) was observed with two human immunoglobulin G1 monoclonal
      antibodies (MAbs) at concentrations of between 2.5 and 10 microg/ml. A
      hyperimmune rabbit antiserum to an E2 hypervariable region 1 (HVR1) mimotope also
      exhibited an HCV E2 pseudotype virus neutralization titer of approximately 1/50.
      An E1 pseudotype virus used as a negative control was not neutralized to a
      significant level (<1/10) by these MAbs or rabbit antiserum to E2 HVR1. Since HCV
      probably has a lipid envelope, the role of complement in antibody-mediated virus
      neutralization was examined. Significant increases in the neutralization titers
      of the human MAbs (approximately 60- to 160-fold higher) and rabbit antiserum to
      HVR1 mimotopes (approximately 10-fold higher) were observed upon addition of
      guinea pig complement. Further, these studies suggested that complement
      activation occurred primarily by the classical pathway, since a deficiency in the
      C4 component led to a significant decrease in the level of virus neutralization.
      This same decrease was not observed with factor B-deficient complement. We also
      determined that 9 of 56 HCV-infected patient sera (16%) had detectable pseudotype
      virus neutralization activity at serum dilutions of between 1/20 and 1/50 and
      that complement addition enhanced the neutralization activity of some of the HCV
      infected human sera. Taken together, these results suggest that during infection,
      HCV E2 glycoprotein induces a weak neutralizing antibody response, that those
      antibodies can be measured in vitro by the surrogate pseudotype virus plaque
      reduction assay, and that neutralization function can be augmented by complement.

PMID- 11836393
TI  - Degradation of STAT1 and STAT2 by the V proteins of simian virus 5 and human
      parainfluenza virus type 2, respectively: consequences for virus replication in
      the presence of alpha/beta and gamma interferons.
AB  - Human cell lines were isolated that express the V protein of either simian virus
      5 (SV5) or human parainfluenza virus type 2 (hPIV2); the cell lines were termed
      2f/SV5-V and 2f/PIV2-V, respectively. STAT1 was not detectable in 2f/SV5-V cells,
      and the cells failed to signal in response to either alpha/beta interferons (IFN
      alpha and IFN-beta, or IFN-alpha/beta) or gamma interferon (IFN-gamma). In
      contrast, STAT2 was absent from 2f/PIV2-V cells, and IFN-alpha/beta but not IFN
      gamma signaling was blocked in these cells. Treatment of both 2f/SV5-V and
      2f/PIV2-V cells with a proteasome inhibitor allowed the respective STAT levels to
      accumulate at rates similar to those seen in 2fTGH cells, indicating that the V
      proteins target the STATs for proteasomal degradation. Infection with SV5 can
      lead to a complete loss of both phosphorylated and nonphosphorylated forms of
      STAT1 by 6 h postinfection. Since the turnover of STAT1 in uninfected cells is
      longer than 24 h, we conclude that degradation of STAT1 is the main mechanism by
      which SV5 blocks interferon (IFN) signaling. Pretreatment of 2fTGH cells with IFN
      alpha severely inhibited both SV5 and hPIV2 protein synthesis. However, and in
      marked contrast, pretreatment of 2fTGH cells with IFN-gamma had little obvious
      effect on SV5 protein synthesis but did significantly reduce the replication of
      hPIV2. Pretreament with IFN-alpha or IFN-gamma did not induce an antiviral state
      in 2f/SV5-V cells, indicating either that the induction of an antiviral state is
      completely dependent on STAT signaling or that the V protein interferes with
      other, STAT-independent cell signaling pathways that may be induced by IFNs. Even
      though SV5 blocked IFN signaling, the addition of exogenous IFN-alpha to the
      culture medium of 2fTGH cells 12 h after a low-multiplicity infection with SV5
      significantly reduced the subsequent cell-to-cell spread of virus. The
      significance of the results in terms of the strategy that these viruses have
      evolved to circumvent the IFN response is discussed.

PMID- 11836394
TI  - CDP binding to multiple sites in the mouse mammary tumor virus long terminal
      repeat suppresses basal and glucocorticoid-induced transcription.
AB  - Mouse mammary tumor virus (MMTV) is transcribed at high levels in the lactating
      mammary gland to ensure transmission of virus from the milk of infected female
      mice to susceptible offspring. We previously have shown that the transcription
      factor CCAAT displacement protein (CDP) is expressed in high amounts in virgin
      mammary gland, yet DNA-binding activity for the MMTV long terminal repeat (LTR)
      disappears as mammary tissue differentiates during lactation. CDP is a repressor
      of MMTV expression and, therefore, MMTV expression is suppressed during early
      mammary gland development. In this study, we have shown using DNase I
      footprinting and electrophoretic mobility shift assays that there are at least
      five CDP-binding sites in the MMTV LTR upstream of those previously described in
      the promoter-proximal negative regulatory element (NRE). Single mutations in two
      of these upstream sites (+691 or +692 and +735 relative to the first base of the
      LTR) reduced CDP binding to the cognate sites and elevated reporter gene
      expression from the full-length MMTV LTR. Combination of a mutation in the
      promoter-distal NRE with a mutation in the proximal NRE gave approximately
      additive increases in LTR-reporter gene activity, suggesting that these binding
      sites act independently. Mutations in several different CDP-binding sites allowed
      elevation of reporter gene activity from the MMTV promoter in the absence and
      presence of glucocorticoids, hormones that contribute to high levels of MMTV
      transcription during lactation by activation of hormone receptor binding to the
      LTR. In addition, overexpression of CDP in transient-transfection assays
      suppressed both basal and glucocorticoid-induced LTR-mediated transcription in a
      dose-dependent manner. These data suggest that multiple CDP-binding sites
      contribute independently to regulate binding of positive factors, including
      glucocorticoid receptor, to the MMTV LTR during mammary gland development.

PMID- 11836395
TI  - Expression of herpes simplex virus ICP0 inhibits the induction of interferon
      stimulated genes by viral infection.
AB  - The herpes simplex virus type 1 (HSV-1) mutant d109 does not express any of the
      immediate-early (IE) proteins and persists in cells for a prolonged length of
      time. As has been shown by Nicholl et al. (J. Gen. Virol. 81:2215-2218, 2000) and
      Mossman et al. (J. Virol. 75:750-758, 2001) using other mutants defective for IE
      gene expression, infection with d109 induced the expression of a number of
      interferon-stimulated genes. Induction of these genes was significantly greater
      at multiplicities of infection (MOI) of 10 PFU/cell or greater, and the resulting
      antiviral effect was only seen at MOIs greater than 10 PFU/cell. Using mutants
      defective for sets of IE genes established that the lack of ICP0 expression was
      necessary for high levels of interferon-stimulated gene expression in HEL cells.
      The induction of interferon-stimulated genes by d109 could also be inhibited by
      infection with an E1-:E3-:E4- adenovirus expressing levels of ICP0 that are
      comparable to those expressed within the first hour of wild-type virus infection.
      Lastly, the addition of the proteasome inhibitor MG132 to cells infected with a
      mutant that expresses ICP0, d106, also resulted in the induction of interferon
      stimulated genes. Thus, ICP0 may function through the proteasome very early in
      HSV infection to inhibit a cellular antiviral response induced by the virion.

PMID- 11836396
TI  - High-throughput selection of retrovirus producer cell lines leads to markedly
      improved efficiency of germ line-transmissible insertions in zebra fish.
AB  - Vesicular stomatitis virus glycoprotein G-pseudotyped mouse retroviral vectors
      have been used as mutagens for a large-scale insertional mutagenesis screen in
      the zebra fish. To reproducibly generate high-titer virus stocks, we devised a
      method for rapidly selecting cell lines that can yield high-titer viruses and
      isolated a producer cell line that yields virus at a high titer on zebra fish
      embryos. Virus produced from this line, designated GT virus, is nontoxic
      following injection of zebra fish blastulae and efficiently infects embryonic
      cells that give rise to the future germ line. Using GT virus preparations we
      generated roughly 500,000 germ line-transmissible proviral insertions in a
      population of 25,000 founder fish in about 2 months. The GT virus contains a gene
      trap, and trap events can be detected in the offspring of almost every founder
      fish. We discuss potential applications of this highly efficient method for
      generating germ line-transmissible insertions in a vertebrate

PMID- 11836397
TI  - Altering the expression kinetics of VP5 results in altered virulence and
      pathogenesis of herpes simplex virus type 1 in mice.
AB  - While many herpes simplex virus (HSV) structural proteins are expressed with
      strict-late kinetics, the HSV virion protein 5 (VP5) is expressed as a "leaky
      late" protein, such that appreciable amounts of VP5 are made prior to DNA
      replication. Our goal has been to determine if leaky-late expression of VP5 is a
      requirement for a normal HSV infection. It had been shown previously that
      recombinant viruses in which the VP5 promoter was replaced with promoters of
      other kinetic classes (including a strict late promoter) exhibited no alterations
      in replication kinetics or virus yields in vitro. In contrast, here we report
      that alterations in pathogenesis were observed when these recombinants were
      analyzed by experimental infection of mice. Following intracranial inoculation, a
      recombinant expressing VP5 from a strict-late promoter (U(L)38) exhibited an
      increased 50% lethal dose and a 10-fold decrease in virus yields in the central
      nervous system, while a recombinant expressing VP5 from an early (dUTPase) or
      another leaky-late (VP16) promoter exhibited wild-type neurovirulence. Moreover,
      following infection of the footpad, changing the expression kinetics of VP5 from
      leaky-late to strict-late resulted in 100-fold-less virus in the spinal ganglia
      during the acute infection than produced by either the parent virus or the
      rescued virus. These data indicate that the precise timing of appearance of the
      major capsid protein plays a role in the pathogenesis of HSV infections and that
      changing the expression kinetics has different effects in different cell types
      and tissues.

PMID- 11836399
TI  - Chemokine expression in the central nervous system of mice with a viral disease
      resembling multiple sclerosis: roles of CD4+ and CD8+ T cells and viral
      persistence.
AB  - During the first 45 days after intracerebral infection with Theiler's murine
      encephalomyelitis virus (TMEV), the levels of mRNAs encoding chemokines MCP
      1/CCL2, RANTES/CCL5, and IP-10/CXCL10 in the central nervous system (CNS) are
      closely related to the sites of virus gene expression and tissue inflammation. In
      the present study, these chemokines were monitored during the latter 135 days of
      a 6-month course of TMEV-induced disease in susceptible (PLJ) or resistant
      (C57BL/6) mice that possessed or lacked either CD4+ or CD8+ T cells. These data
      were additionally correlated to mouse genotype, virus persistence in the CNS,
      antiviral antibody titers, mortality, and the severity of neurological disease.
      Surprisingly, the major determinant of chemokine expression was virus
      persistence: the factors of susceptible or resistant genotype, severity of
      neuropathology, and presence or absence of regulatory T cells exerted minimal
      effects. Our observations indicated that chemokine expression in the CNS in this
      chronic viral disorder was intrinsic to the CNS innate immune response to
      infection and was not governed by elements of the adaptive immune system.

PMID- 11836398
TI  - Safety and immunogenicity of ALVAC vCP1452 and recombinant gp160 in newly human
      immunodeficiency virus type 1-infected patients treated with prolonged highly
      active antiretroviral therapy.
AB  - In order to boost immune responses in persons in whom highly active
      antiretroviral therapy (HAART) was initiated within 120 days of the onset of
      symptoms of newly acquired human immunodeficiency virus type 1 (HIV-1) infection,
      we administered vaccines containing a canarypox virus vector, vCP1452, with HIV-1
      genes encoding multiple HIV-1 proteins, and recombinant gp160. Fifteen HIV-1
      infected subjects who achieved sustained suppression of plasma viremia for at
      least 2 years were enrolled. While continuing antiretroviral therapy, each
      subject received at least four intramuscular injections of the vaccines on days
      0, 30, 90, and 180. Adverse events were mild, with the most common being
      transient tenderness at the vCP1452 injection site. Of the 14 patients who
      completed vaccination, 13 had significant increases in anti-gp120 or anti-p24
      antibody titers, and 9 had transient augmentation of their T-cell proliferation
      responses to gp160 and/or p24. HIV-1-specific CD8(+) T cells were quantified
      using an intracellular gamma interferon staining assay. Among 11 patients who had
      increased CD8(+) T-cell responses, seven had responses to more than one HIV-1
      antigen. In summary, vaccination with vCP1452 and recombinant gp160 appears safe
      and immunogenic in newly HIV-1-infected patients on HAART.

PMID- 11836400
TI  - Temporal effects of gamma interferon deficiency on the course of Friend
      retrovirus infection in mice.
AB  - The current studies demonstrate complex and seemingly contradictory effects by
      gamma interferon (IFN-gamma) on Friend virus (FV) infection. Both temporal and
      tissue-specific effects were observed. During the first week of infection, IFN
      gamma-deficiency caused increased levels of FV infection in multiple tissues.
      Surprisingly, however, by 2 weeks postinfection, IFN-gamma-deficient mice had
      significantly lower levels of infection in both the spleen and bone marrow
      compared to wild-type mice. The rapid reduction of virus in the IFN-gamma
      deficient mice correlated with a more rapid virus-neutralizing antibody response
      than was observed in the wild-type mice. Furthermore, the virus-neutralizing
      antibody response in wild-type mice could be accelerated by ablation of their IFN
      gamma response. Although the IFN-gamma-deficient mice developed an accelerated
      virus-neutralizing antibody response, they did not class-switch to immunoglobulin
      G class immunoglobulins nor could they maintain long-term virus-neutralizing
      antibody titers. Eventually, all of the IFN-gamma-deficient mice failed to keep
      persistent virus in check and developed fatal FV-induced erythroleukemia.

PMID- 11836401
TI  - Regional clustering of shared neutralization determinants on primary isolates of
      clade C human immunodeficiency virus type 1 from South Africa.
AB  - Clade C is one of the most prevalent genetic subtypes of human immunodeficiency
      virus type 1 (HIV-1) in the world today and one of the least studied with respect
      to neutralizing antibodies. Most information on HIV-1 serology as it relates to
      neutralization is derived from clade B. Clade C primary isolates of HIV-1 from
      South Africa and Malawi were shown here to resemble clade B isolates in their
      resistance to inhibition by soluble CD4 and their sensitivity to neutralization
      by human monoclonal antibody immunoglobulin G1b12 and, to a lesser extent, 2F5.
      Unlike clade B isolates, however, all 16 clade C isolates examined resisted
      neutralization by 2G12. Infection with clade C HIV-1 in a cohort of female sex
      workers in South Africa generated antibodies that neutralized the autologous
      clade C isolate and T-cell-line-adapted (TCLA) strains of clade B. Neutralization
      of clade B TCLA strains was much more sensitive to the presence of autologous
      gp120 V3 loop peptides compared to the neutralization of clade C isolates in most
      cases. Thus, the native structure of gp120 on primary isolates of clade C will
      likely pose a challenge for neutralizing antibody induction by candidate HIV-1
      vaccines much the same as it has for clade B. The autologous neutralizing
      antibody response following primary infection with clade C HIV-1 in South Africa
      matured slowly, requiring at least 4 to 5 months to become detectable. Once
      detectable, extensive cross-neutralization of heterologous clade C isolates from
      South Africa was observed, suggesting an unusual degree of shared neutralization
      determinants at a regional level. This high frequency of cross-neutralization
      differed significantly from the ability of South African clade C serum samples to
      neutralize clade B isolates but did not differ significantly from results of
      other combinations of clade B and C reagents tested in checkerboard assays.
      Notably, two clade C serum samples obtained after less than 2 years of infection
      neutralized a broad spectrum of clade B and C isolates. Other individual serum
      samples showed a significant clade preference in their neutralizing activity. Our
      results suggest that clades B and C are each comprised of multiple neutralization
      serotypes, some of which are more clade specific than others. The clustering of
      shared neutralization determinants on clade C primary HIV-1 isolates from South
      Africa suggests that neutralizing antibodies induced by vaccines will have less
      epitope diversity to overcome at a regional level.

PMID- 11836402
TI  - Interaction of the CC-chemokine RANTES with glycosaminoglycans activates a
      p44/p42 mitogen-activated protein kinase-dependent signaling pathway and enhances
      human immunodeficiency virus type 1 infectivity.
AB  - The interaction of the CC-chemokine RANTES with its cell surface receptors
      transduces multiple intracellular signals: low concentrations of RANTES (1 to 10
      nM) stimulate G-protein-coupled receptor (GPCR) activity, and higher
      concentrations (1 microM) activate a phosphotyrosine kinase (PTK)-dependent
      pathway. Here, we show that the higher RANTES concentrations induce rapid
      tyrosine phosphorylation of multiple proteins. Several src-family kinases (Fyn,
      Hck, Src) are activated, as is the focal adhesion kinase p125 FAK and,
      eventually, members of the p44/p42 mitogen-activated protein kinase (MAPK)
      family. This PTK signaling pathway can be activated independently of known seven
      transmembrane GPCRs for RANTES because it occurs in cells that lack any such
      RANTES receptors. Instead, activation of the PTK signaling pathway is dependent
      on the expression of glycosaminoglycans (GAGs) on the cell surface, in that it
      could not be activated by RANTES in GAG-deficient cells. We have previously
      demonstrated that RANTES can both enhance and inhibit infection of cells with
      human immunodeficiency virus type 1 (HIV-1). Here we show that activation of both
      PTK and MAPK is involved in the enhancement of HIV-1 infectivity caused by RANTES
      in cells that lack GPCRs for RANTES but which express GAGs.

PMID- 11836403
TI  - trans-Complementation rescue of cyclophilin A-deficient viruses reveals that the
      requirement for cyclophilin A in human immunodeficiency virus type 1 replication
      is independent of its isomerase activity.
AB  - Human immunodeficiency virus type 1 (HIV-1) requires the incorporation of
      cyclophilin A (CypA) for replication. CypA is packaged by binding to the capsid
      (CA) region of Gag. This interaction is disrupted by cyclosporine (CsA).
      Preventing CypA incorporation, either by mutations in the binding region of CA or
      by the presence of CsA, abrogates virus infectivity. Given that CypA possesses an
      isomerase activity, it has been proposed that CypA acts as an uncoating factor by
      destabilizing the shell of CA that surrounds the viral genome. However, because
      the same domain of CypA is responsible for both its isomerase activity and its
      capacity to be packaged, it has been challenging to determine if isomerase
      activity is required for HIV-1 replication. To address this issue, we fused CypA
      to viral protein R (Vpr), creating a Vpr-CypA chimera. Because Vpr is packaged
      via the p6 region of Gag, this approach bypasses the interaction with CA and
      allows CypA incorporation even in the presence of CsA. Using this system, we
      found that Vpr-CypA rescues the infectivity of viruses lacking CypA, either
      produced in the presence of CsA or mutated in the CypA packaging signal of CA.
      Furthermore, a Vpr-CypA mutant which has no isomerase activity and no capacity to
      bind to CA also rescues HIV-1 replication. Thus, this study demonstrates that the
      isomerase activity of CypA is not required for HIV-1 replication and suggests
      that the interaction of the catalytic site of CypA with CA serves no other
      function than to incorporate CypA into viruses.

PMID- 11836404
TI  - Human papillomavirus type 31 replication modes during the early phases of the
      viral life cycle depend on transcriptional and posttranscriptional regulation of
      E1 and E2 expression.
AB  - The E1 and E2 proteins are both required for papillomavirus DNA replication, and
      replication efficiency is controlled by the abundance of these factors. In human
      papillomaviruses (HPVs), the regulation of E1 and E2 expression and its effect on
      viral replication are not well understood. In particular, it is not known if E1
      and E2 modulate their own expression and how posttranscriptional mechanisms may
      affect the levels of the replication proteins. Previous studies have implicated
      splicing within the E6 open reading frame (ORF) as being important for modulating
      replication of HPV type 31 (HPV31) through altered expression of E1 and E2. To
      analyze the function of the E6 intron in viral replication more specifically, we
      examined the effects of E6 splicing mutations in the context of entire viral
      genomes in transient assays. HPV31 genomes which had mutations in the splice
      donor site (E6SD) or the splice acceptor site (E6SA), a deletion of the intron
      (E6ID), or substituted heterologous intron sequences (E6IS) were constructed.
      Compared to wild-type (wt) HPV31, pHPV31-E6SD, -E6SA, and -E6IS replicated
      inefficiently while pHPV31-E6ID replicated at an intermediate level.
      Cotransfection of the E6 mutant genomes with an E1 expression vector strongly
      activated their replication levels, indicating that efficient expression of E1
      requires E6 internal splicing. In contrast, replication was activated only
      moderately with an E2 expression vector. Replacing the wt E6 intron in HPV31 with
      a heterologous intron from simian virus 40 (E6SR2) resulted in replication levels
      similar to that of the wt in the absence of expression vectors, suggesting that
      mRNA splicing upstream of the E1 ORF is important for high-level replication. To
      examine the effects of E6 intron splicing on E1 and E2 expression directly, we
      constructed reporter DNAs in which the luciferase coding sequences were fused in
      frame to the E1 (E1Luc) or E2 (E2Luc) gene. Reporter activities were then
      analyzed in transient assays with cotransfected E1 or E2 expression vectors. Both
      reporters were moderately activated by E1 in a dose-dependent manner. In
      addition, E1Luc was activated by low doses of E2 but was repressed at high doses.
      In contrast, E2 had little effect on E2Luc activity. These data indicate that E1
      expression and that of E2 are interdependent and regulated differentially. When
      the E6 splicing mutations were analyzed in both reporter backgrounds, only E1Luc
      activities correlated with splicing competence in the E6 ORF. These findings
      support the hypothesis that the E6 intron primarily regulates expression of E1.
      Finally, in long-term replication assays, none of the E6 mutant genomes could be
      stably maintained. However, cotransfection of the E6 splicing mutant genomes with
      pHPV31-E7NS, which contains a nonsense mutation in the E7 coding sequence,
      restored stable replication of some mutants. Our observations indicate that E1
      expression and that of E2 are differentially regulated at multiple levels and
      that efficient expression of E1 is required for transient and stable viral
      replication. These regulatory mechanisms likely act to control HPV copy number
      during the various phases of the viral life cycle.

PMID- 11836405
TI  - Complementary antiviral efficacy of hydroxyurea and protease inhibitors in human
      immunodeficiency virus-infected dendritic cells and lymphocytes.
AB  - Dendritic cells are susceptible to human immunodeficiency virus (HIV) infection
      and may transmit the virus to T cells in vivo. Scarce information is available
      about drug efficacy in dendritic cells because preclinical testing of
      antiretroviral drugs has been limited predominantly to T cells and macrophages.
      We compared the antiviral activities of hydroxyurea and two protease inhibitors
      (indinavir and ritonavir) in monocyte-derived dendritic cells and in lymphocytes.
      At therapeutic concentrations (50 to 100 microM), hydroxyurea inhibited
      supernatant virus production from monocyte-derived dendritic cells in vitro but
      the drug was ineffective in activated lymphocytes. Concentrations of hydroxyurea
      insufficient to be effective in activated lymphocytes cultured alone strongly
      inhibited supernatant virus production from cocultures of uninfected, activated
      lymphocytes with previously infected monocyte-derived dendritic cells in vitro.
      In contrast, protease inhibitors were up to 30-fold less efficient in dendritic
      cells than in activated lymphocytes. Our data support the rationale for testing
      of the combination of hydroxyurea and protease inhibitors, since these drugs may
      have complementary antiviral efficacies in different cell compartments. A new
      criterion for combining drugs for the treatment of HIV infection could be to
      include at least one drug that selectively targets HIV in viral reservoirs.

PMID- 11836406
TI  - Genetic control of a mouse serum lipoprotein factor that inactivates murine
      leukemia viruses: evaluation of apolipoprotein F as a candidate.
AB  - Mice contain a serum factor capable of inactivating some subgroups of murine
      leukemia viruses. This leukemia virus-inactivating factor (LVIF) is distinct from
      immunoglobulin and complement; it has been associated with lipoprotein serum
      fractions and may be an apolipoprotein. The present study demonstrates that some
      Swiss-derived inbred strains are LVIF negative. Genetic crosses show this factor
      to be under control of a single gene that maps to distal chromosome 10 at or near
      the gene encoding a minor serum apolipoprotein, apolipoprotein F (ApoF). To
      evaluate this gene as a potential candidate for LVIF, the mouse ApoF gene was
      cloned and sequenced and its expression was assessed in LVIF-positive and 
      negative mice; no obvious differences were detected, suggesting that LVIF is
      under the control of a distinct linked gene.

PMID- 11836407
TI  - Baculovirus replication factor LEF-1 is a DNA primase.
AB  - The baculovirus replication factors LEF-1 and LEF-2 of the Autographa californica
      multinucleocapsid nucleopolyhedrovirus were overexpressed as fusions containing a
      hemagglutinin (HA) epitope and a HIS(6) tag using recombinant baculoviruses. LEF
      1 was purified to near homogeneity and found to have primase activity in an
      indirect assay employing Escherichia coli DNA polymerase I (Klenow enzyme) and
      poly(dT) template. The LEF-1 primase products were also directly characterized by
      electrophoresis in 20% polyacrylamide-8 M urea gels and agarose gels. Primer
      synthesis was time dependent, and products of several hundred nucleotides or more
      were observed from the M13 single-stranded DNA (ssDNA) template. The LEF-1
      primase was absolutely dependent on divalent cations (Mg(2+)), and optimal
      activity was supported by 10 mM MgCl(2). An alkaline pH (8.8 to 9.4) was optimal,
      whereas monovalent salt (KCl) was inhibitory. Mutation of an invariant aspartic
      acid in a putative primase domain caused LEF-1 activity to be abolished. Upon
      ultracentrifugation in glycerol gradients, LEF-1 was found to have a
      sedimentation coefficient of 3S that is consistent with its being present as a
      monomer. Elution profiles of LEF-1 and LEF-2 from ssDNA-cellulose and DEAE resin
      suggested that LEF-2 may bind to both DNA and LEF-1.

PMID- 11836408
TI  - Magnitude of functional CD8+ T-cell responses to the gag protein of human
      immunodeficiency virus type 1 correlates inversely with viral load in plasma.
AB  - The importance of CD8+ T-cell responses in the control of human immunodeficiency
      virus type 1 (HIV-1) infection has been demonstrated, yet few studies have been
      able to correlate these responses with markers of HIV-1 disease progression. This
      study measured cell-mediated immune responses using peripheral blood mononuclear
      cells (PBMC) obtained from 27 patients with chronic HIV-1 infection, the majority
      of whom were off antiretroviral therapy. The ELISPOT assay was used to detect
      gamma interferon-secreting PBMC after stimulation with overlapping HIV-1 peptides
      spanning the Gag, Pol, Env, and Nef proteins in addition to the baculovirus
      derived p24 and gp160 proteins. All volunteers had responses to at least one HIV
      1-specific peptide. All but one of the subjects (96%) responded to the Gag
      peptide pool, and 86% responded to the Pol and/or Nef peptide pools. The
      magnitude and the breadth of T-cell responses directed to either the Gag or p24
      peptide pools correlated inversely with viral load in plasma (r = -0.60, P <
      0.001 and r = -0.52, P < 0.005, respectively) and directly with absolute CD4+ T
      cell counts (r = 0.54, P < 0.01 and r = 0.39, P < 0.05, respectively) using the
      Spearman rank correlation test. Responses to the Pol and integrase peptide pools
      also correlated with absolute CD4+ T-cell counts (r = 0.45, P < 0.05 and r =
      0.49, P < 0.01, respectively). No correlation with markers of disease progression
      was seen with specific T-cell responses directed toward the Env or Nef peptides.
      These data serve as strong evidence that major histocompatibility complex class I
      presentation of Gag peptides is an essential feature for any HIV-1 vaccine
      designed to elicit optimal CD8+ T-cell responses.

PMID- 11836409
TI  - Longitudinal analysis of feline leukemia virus-specific cytotoxic T lymphocytes:
      correlation with recovery from infection.
AB  - Feline leukemia virus (FeLV) is a common naturally occurring gammaretrovirus of
      domestic cats that is associated with degenerative diseases of the hematopoietic
      system, immunodeficiency, and neoplasia. Although the majority of cats exposed to
      FeLV develop a transient infection and recover, a proportion of cats become
      persistently viremic and many subsequently develop fatal diseases. To define the
      dominant host immune effector mechanisms responsible for the outcome of
      infection, we studied the longitudinal changes in FeLV-specific cytotoxic T
      lymphocytes (CTLs) in a group of naive cats following oronasal exposure to FeLV.
      Using (51)Cr release assays to measure ex vivo virus-specific cytotoxicity, the
      emerging virus-specific CTL response was correlated with modulations in viral
      burden as assessed by detection of infectious virus, FeLV p27 capsid antigen, and
      proviral DNA in the blood. High levels of circulating FeLV-specific effector CTLs
      appeared before virus neutralizing antibodies in cats that recovered from
      exposure to FeLV. In contrast, persistent viremia was associated with a silencing
      of virus-specific humoral and cell-mediated host immune effector mechanisms. A
      single transfer of between 2 x 10(7) and 1 x 10(8) autologous, antigen-activated
      lymphoblasts was associated with a downmodulation in viral burden in vivo. The
      results suggest an important role for FeLV-specific CTLs in retroviral immunity
      and demonstrate the potential to modulate disease outcome by the adoptive
      transfer of antigen-specific T cells in vivo.

PMID- 11836410
TI  - Construction of a self-excisable bacterial artificial chromosome containing the
      human cytomegalovirus genome and mutagenesis of the diploid TRL/IRL13 gene.
AB  - The full-length genome of human cytomegalovirus strain AD169 was cloned as an
      infectious bacterial artificial chromosome (BAC) plasmid, pAD/Cre. The BAC
      vector, flanked by LoxP sites, was inserted immediately after the Us28 open
      reading frame without deletion of any viral sequences. The BAC vector contained
      the Cre recombinase-encoding gene disrupted by an intron under control of the
      simian virus 40 early promoter. When pAD/Cre was transfected into primary human
      foreskin fibroblast cells, Cre was expressed and mediated site-specific
      recombination between the two LoxP sites, excising the BAC DNA backbone. This
      gave rise to progeny virus that was wild type with the exception of an inserted
      34-bp LoxP site. We performed site-directed mutagenesis on pAD/Cre to generate a
      series of viruses in which the TRL/IRL13 diploid genes were disrupted and
      subsequently repaired. The mutants reach the same titer as the wild-type virus,
      indicating that the TRL/IRL13 open reading frames are not required for virus
      growth in cell culture. The sequence of the TRL13 open reading frame in the low
      passage Toledo strain of human cytomegalovirus is quite different from the
      corresponding region in the AD169 strain. One of multiple changes is a frameshift
      mutation. As a consequence, strain Toledo encodes a putative TRL13 protein whose
      C-terminal domain is larger (extending through the TRL14 coding region) and
      encodes in a reading frame different from that of strain AD169. We speculate that
      the strain AD169 coding region has drifted during passage in the laboratory. We
      propose that TRL13 has been truncated in strain AD169 and that the partially
      overlapping TRL14 open reading frame is not functional. This view is consistent
      with the presence of both TRL13 and -14 on all mRNAs that we have mapped from
      this region, an organization that would include the much longer strain Toledo
      TRL13 open reading frame on the mRNAs.

PMID- 11836411
TI  - The tRNA primer activation signal in the human immunodeficiency virus type 1
      genome is important for initiation and processive elongation of reverse
      transcription.
AB  - Human immunodeficiency virus type 1 (HIV-1) reverse transcription is primed by
      the cellular tRNA(3)(Lys) molecule, which binds, with its 3"-terminal 18
      nucleotides (nt), to a complementary sequence in the viral genome, the primer
      binding site (PBS). Besides PBS-anti-PBS pairing, additional interactions between
      viral RNA sequences and the tRNA primer are thought to regulate the process of
      reverse transcription. We previously identified a novel 8-nt sequence motif in
      the U5 region of the HIV-1 RNA genome that is critical for tRNA(3)(Lys)-mediated
      initiation of reverse transcription in vitro. This motif activates initiation
      from the natural tRNA(3)(Lys) primer but is not involved in tRNA placement and
      was therefore termed primer activation signal (PAS). It was proposed that the PAS
      interacts with the anti-PAS motif in the TphiC arm of tRNA(3)(Lys). In this
      study, we analyzed several PAS-mutated viruses and performed reverse
      transcription assays with virion-extracted RNA-tRNA complexes. Mutation of the
      PAS reduced the efficiency of tRNA-primed reverse transcription. In contrast,
      mutations in the opposing leader sequence that trigger release of the PAS from
      base pairing stimulated reverse transcription. These results are similar to the
      reverse transcription effects observed in vitro. We also selected revertant
      viruses that partially overcome the reverse transcription defect of the PAS
      deletion mutant. Remarkably, all revertants acquired a single nucleotide
      substitution that does not restore the PAS sequence but that stimulates
      elongation of reverse transcription. These combined results indicate that the
      additional PAS-anti-PAS interaction is needed to assemble an initiation-competent
      and processive reverse transcription complex.

PMID- 11836412
TI  - Endocytosis of adeno-associated virus type 5 leads to accumulation of virus
      particles in the Golgi compartment.
AB  - Among the adeno-associated virus (AAV) serotypes which are discussed as vectors
      for gene therapy AAV type 5 (AAV5) represents a candidate with unique advantages.
      To further our knowledge on AAV5-specific characteristics, we studied the entry
      pathway of wild-type virus in HeLa cells in the absence of helper virus by
      immunofluorescence and electron microscopy and by Western blot analysis. We found
      virus binding at the apical cell surface, especially at microvilli and, with
      increasing incubation time, virus accumulation at cell-cell boundaries. The
      different binding kinetics suggest different binding properties at apical versus
      lateral plasma membranes. Endocytosis of viruses was predominantly by clathrin
      coated vesicles from both membrane domains; however, particles were also detected
      in noncoated pits. AAV5 particles were mainly routed to the Golgi area, where
      they could be detected within cisternae of the trans-Golgi network and within
      vesicles associated with cisternae and with the dictyosomal stacks of the Golgi
      apparatus. These data suggest that AAV5 makes use of endocytic routes that have
      hitherto not been described as pathways for virus entry.

PMID- 11836413
TI  - An endoplasmic reticulum protein, p180, is highly expressed in human
      cytomegalovirus-permissive cells and interacts with the tegument protein encoded
      by UL48.
AB  - We have used a virus overlay assay to detect cellular proteins associated with
      human cytomegalovirus (HCMV) particles. The radiolabeled HCMV particles
      specifically bound to two host proteins with molecular sizes of 150 and 180 kDa.
      By a micro-amino-acid sequencing technique, the 180-kDa protein was identified as
      a human homologue of the ES130/p180 ribosome receptor (p180), which is an
      integral endoplasmic reticulum (ER) membrane protein possessing a very unique
      tandem repeat domain at its N-terminal region. The virus overlay assay using
      truncated p180 polypeptides revealed that HCMV binding to human p180 occurred
      through the N-terminal region. In HCMV-permissive cells the high level of
      expression of the human p180 protein was clearly observed regardless of cell
      type. Furthermore, we showed that p180 binds to the UL48 gene product, which is
      one of the predominant tegument proteins of HCMV and which is considered to be
      tightly associated with the capsid. The interaction between the two proteins was
      assumed to be specific and was observed both in vitro and in vivo. During the
      late phase of infection, the unique relocation of human p180 was observed, that
      is, to the juxtanuclear region, which appeared to be in the vicinity of the area
      where naked virions were frequently observed in an electron-microscopic study.
      Thus our data suggest that p180 interacts with the HCMV tegument, at least
      through pUL48, during the HCMV replication process. We discuss the possible role
      of the interaction between p180 and pUL48 in the intracellular transport of HCMV
      virions.

PMID- 11836414
TI  - Disruption of hematopoiesis and thymopoiesis in the early premalignant stages of
      infection with SL3-3 murine leukemia virus.
AB  - A time course analysis of SL3-3 murine leukemia virus (SL3) infection in thymus
      and bone marrow of NIH/Swiss mice was performed to assess changes that occur
      during the early stages of progression to lymphoma. Virus was detectable in
      thymocytes, bone marrow, and spleen as early as 1 to 2 weeks postinoculation
      (p.i.). In bone marrow, virus infection was detected predominantly in immature
      myeloid or granulocytic cells. Flow cytometry revealed significant reductions of
      the Ter-119(+) and Mac-1(+) populations, and significant expansions of the Gr
      1(+) and CD34(+) populations, between 2 and 4 weeks p.i. Analysis of colony
      forming potential confirmed these findings. In the thymus, SL3 replication was
      associated with significant disruption in thymocyte subpopulation distribution
      between 4 and 7 weeks p.i. A significant thymic regression was observed just
      prior to the clonal outgrowth of tumor cells. Proviral long terminal repeats
      (LTRs) with increasing numbers of enhancer repeats were observed to accumulate
      exclusively in the thymus during the first 8 weeks p.i. Observations were
      compared to the early stages of infection with a virtually nonpathogenic SL3
      mutant, termed SL3DeltaMyb5, which was shown by real-time PCR to be replication
      competent. Comparison of SL3 with SL3DeltaMyb5 implicated certain premalignant
      changes in tumorigenesis, including (i) increased proportions of Gr-1(+) and
      CD34(+) bone marrow progenitors, (ii) a significant increase in the proportion of
      CD4(-) CD8(-) thymocytes, (iii) thymic regression prior to tumor outgrowth, and
      (iv) accumulation of LTR enhancer variants. A model in which disrupted bone
      marrow hematopoiesis and thymopoiesis contribute to the development of lymphoma
      in the SL3-infected animal is discussed.

PMID- 11836416
TI  - The maturation process of pVP2 requires assembly of infectious bursal disease
      virus capsids.
AB  - Infectious bursal disease virus (IBDV) is a nonenveloped avian virus with a two
      segment double-stranded RNA genome. Its T=13 icosahedral capsid is most probably
      assembled with 780 subunits of VP2 and 600 copies of VP3 and has a diameter of
      about 60 nm. VP1, the RNA-dependent RNA polymerase, resides inside the viral
      particle. Using a baculovirus expression system, we first observed that
      expression of the pVP2-VP4-VP3 polyprotein encoded by the genomic segment IBDA
      results mainly in the formation of tubules with a diameter of about 50 nm and
      composed of pVP2, the precursor of VP2. Very few virus-like particles (VLPs) and
      VP4 tubules with a diameter of about 25 nm were also identified. The inefficiency
      of VLP assembly was further investigated by expression of additional IBDA-derived
      constructs. Expression of pVP2 without any other polyprotein components results
      in the formation of isometric particles with a diameter of about 30 nm. VLPs were
      observed mainly when a large exogeneous polypeptide sequence (the green
      fluorescent protein sequence) was fused to the VP3 C-terminal domain. Large
      numbers of VLPs were visualized by electron microscopy, and single particles were
      shown to be fluorescent by standard and confocal microscopy analysis. Moreover,
      the final maturation process converting pVP2 into the VP2 mature form was
      observed on generated VLPs. We therefore conclude that the correct scaffolding of
      the VP3 can be artificially induced to promote the formation of VLPs and that the
      final processing of pVP2 to VP2 is controlled by this particular assembly. To our
      knowledge, this is the first report of the engineering of a morphogenesis switch
      to control a particular type of capsid protein assembly.

PMID- 11836415
TI  - Role of an intact splenic microarchitecture in early lymphocytic choriomeningitis
      virus production.
AB  - An acute infection with lymphocytic choriomeningitis virus (LCMV) is efficiently
      controlled by the cytotoxic-T-cell (CTL) response of the host, and LCMV titers in
      the spleen and peripheral solid organs usually fall sharply after day 4 to 6
      postinfection. Surprisingly, infection of immunodeficient recombination
      activating gene 2-deficient (RAG2-/-) mice with 5 x 10(2) PFU of LCMV-WE causes
      about 80-fold-lower LCMV titers in the spleen on day 4 postinfection compared
      with C57BL/6 control mice. This could not be attributed to NK cell activity,
      since common gamma-chain-deficient RAG2-/- mice lacking NK cells show low LCMV
      titers comparable to those for RAG2-/- mice. Furthermore, the reduced early LCMV
      production in spleens could not be explained by an enhanced gamma interferon
      production in RAG2-/- mice. Analysis of mutant mice exhibiting various defects in
      the splenic microarchitecture, including (i) tumor necrosis factor alpha-negative
      (TNF-alpha-/-), lymphotoxin alpha-negative (LTalpha-/-), B-cell-deficient muMT
      mice, (ii) immunoglobulin M-negative mice, and (iii) RAG2-/- mice reconstituted
      with wild-type versus TNF-alpha-/- LTalpha-/- B cells, revealed a clear
      correlation between an intact splenic marginal zone, rapid early replication of
      LCMV in the spleen, and efficient CTL induction. These results suggest that by
      the preferential infection of the highly organized splenic microarchitecture,
      LCMV seems to successfully exploit one of the key elements in the chain of the
      adaptive immune system. Not only does the early tropism of LCMV for the splenic
      marginal zone trigger a potent immune response, but at the same time the marginal
      zone may also become a target of early CTL-mediated immunopathology that impairs
      immune responsiveness.

PMID- 11836417
TI  - The capsid of infectious bursal disease virus contains several small peptides
      arising from the maturation process of pVP2.
AB  - The capsid proteins VP2 and VP3 of infectious bursal disease virus, a birnavirus,
      are derived from the processing of a large polyprotein: NH2-pVP2-VP4-VP3-COOH.
      Although the primary cleavage sites at the pVP2-VP4 and VP4-VP3 junctions have
      been identified, the proteolytic cascade involved in the processing of this
      polyprotein is not yet fully understood, particularly the maturation of pVP2. By
      using different approaches, we showed that the processing of pVP2 (residues 1 to
      512) generated VP2 and four small peptides (residues 442 to 487, 488 to 494, 495
      to 501, and 502 to 512). We also showed that in addition to VP2, at least three
      of these peptides (residues 442 to 487, 488 to 494, and 502 to 512) were
      associated with the viral particles. The importance of the small peptides in the
      virus cycle was assessed by reverse genetics. Our results showed that the mutants
      lacking the two smaller peptides were viable, although the virus growth was
      affected. In contrast, deletions of the domain 442 to 487 or 502 to 512 did not
      allow virus recovery. Several amino acids of the peptide 502 to 512 appeared
      essential for virus viability. Substitutions of the P1 and/or P1" position were
      engineered at each of the cleavage sites (P1-P1": 441-442, 487-488, 494-495, 501
      502, and 512-513). Most substitutions at the pVP2-VP4 junction (512-513) and at
      the final VP2 maturation cleavage site (441-442) were lethal. Mutations of
      intermediate cleavage sites (487-488, 494-495, and 501-502) led to viable viruses
      showing different but efficient pVP2 processing. Our data suggested that while
      peptides 488 to 494 and 495 to 501 play an accessory role, peptides 442 to 487
      and 502 to 512 have an unknown but important function within the virus cycle.

PMID- 11836418
TI  - Measles virus preferentially transduces the basolateral surface of well
      differentiated human airway epithelia.
AB  - Measles virus (MV) is typically spread by aerosol droplets and enters via the
      respiratory tract. The progression of MV infection has been widely studied; yet,
      the pathway for virus entry in polarized human airway epithelia has not been
      investigated. Herein we report the use of a replication-competent Edmonston
      vaccine strain of MV expressing enhanced green fluorescent protein (MV-eGFP) to
      infect primary cultures of well-differentiated human airway epithelia. Previous
      studies with polarized Caco-2 cells (intestine-derived human epithelia) and MDCK
      cells (kidney-derived canine epithelia) demonstrated that MV primarily infected
      and exited the apical surface. In striking contrast, our results indicate that MV
      preferentially transduces human airway cells from the basolateral surface;
      however, virus release remains in an apical direction. When MV-eGFP was applied
      apically or basolaterally to primary cultures of airway epithelia, discrete foci
      of eGFP expression appeared and grew; however, the cell layer integrity was
      maintained for the duration of the study (7 days). Interestingly, utilizing
      immunohistochemistry and confocal microscopy, we observed widespread expression
      of the receptor for the vaccine strain of MV (CD46) at greatest abundance on the
      apical surface of the differentiated human airway epithelia as well as in human
      tracheal tissue sections. These data suggest that the progression of MV infection
      through the respiratory epithelium may involve pathways other than direct binding
      and entry through the apical surface of airway epithelia.

PMID- 11836419
TI  - The solitary long terminal repeats of ERV-9 endogenous retrovirus are conserved
      during primate evolution and possess enhancer activities in embryonic and
      hematopoietic cells.
AB  - The solitary long terminal repeats (LTRs) of ERV-9 endogenous retrovirus contain
      the U3, R, and U5 regions but no internal viral genes. They are middle repetitive
      DNAs present at 2,000 to 4,000 copies in primate genomes. Sequence analyses of
      the 5" boundary area of the erythroid beta-globin locus control region (beta-LCR)
      and the intron of the embryonic axin gene show that a solitary ERV-9 LTR has been
      stably integrated in the respective loci for at least 15 million years in the
      higher primates from orangutan to human. Functional studies utilizing the green
      fluorescent protein (GFP) gene as the reporter in transfection experiments show
      that the U3 region of the LTRs possesses strong enhancer activity in embryonic
      cells of widely different tissue origins and in adult cells of blood lineages. In
      both the genomic LTRs of embryonic placental cells and erythroid K562 cells and
      transfected LTRs of recombinant GFP plasmids in K562 cells, the U3 enhancer
      activates synthesis of RNAs that are initiated from a specific site 25 bases
      downstream of the AATAAA (TATA) motif in the U3 promoter. A second AATAAA motif
      in the R region does not serve as the TATA box or as the polyadenylation signal.
      The LTR-initiated RNAs extend through the R and U5 regions into the downstream
      genomic DNA. The results suggest that the ERV-9 LTR-initiated transcription
      process may modulate transcription of the associated gene loci in embryonic and
      hematopoietic cells.

PMID- 11836420
TI  - Effects of herpes simplex virus on structure and function of nectin-1/HveC.
AB  - Herpes simplex virus (HSV) entry requires the interaction between the envelope
      glycoprotein D (gD) and a cellular receptor such as nectin-1 (also named
      herpesvirus entry mediator C [HveC]) or HveA/HVEM. Nectin-1 is a cell adhesion
      molecule found at adherens junctions associated with the cytoplasmic actin
      binding protein afadin. Nectin-1 can act as its own ligand in a homotypic
      interaction to bridge cells together. We used a cell aggregation assay to map an
      adhesive functional site on nectin-1 and identify the effects of gD binding and
      HSV early infection on nectin-1 function. Soluble forms of nectin-1 and anti
      nectin-1 monoclonal antibodies were used to map a functional adhesive site within
      the first immunoglobulin-like domain (V domain) of nectin-1. This domain also
      contains the gD-binding site, which appeared to overlap the adhesive site. Thus,
      soluble forms of gD were able to prevent nectin-1-mediated cell aggregation and
      to disrupt cell clumps in an affinity-dependent manner. HSV also prevented nectin
      1-mediated cell aggregation by occupying the receptor. Early in infection, nectin
      1 was not downregulated from the cell surface. Rather, detection of nectin-1
      changed gradually over a 30-min period of infection, as reflected by a decrease
      in the CK41 epitope and an increase in the CK35 epitope. The level of detection
      of virion gD on the cell surface increased within 5 min of infection in a
      receptor-dependent manner. These observations suggest that cell surface nectin-1
      and gD may undergo conformational changes during HSV entry as part of an evolving
      interaction between the viral envelope and the cell plasma membrane.

PMID- 11836421
TI  - PrP expression and replication by Schwann cells: implications in prion spreading.
AB  - Prion infection relies on a continuous chain of PrP(c)-expressing tissues to
      spread from peripheral sites to the central nervous system (CNS). Direct
      neuroinvasion via peripheral nerves has long been considered likely. However, the
      speed of axonal flow is incompatible with the lengthy delay prior to the
      detection of PrP(Sc) in the brain. We hypothesized that Schwann cells could be
      the candidate implicated in this mechanism; for that, it has to express PrP(c)
      and to allow PrP(Sc) conversion. We investigated in vivo localization of PrP(c)
      in sciatic nerve samples from different strains of mice. We demonstrated that
      PrP(c) is mainly localized at the cell membrane of the Schwann cell. We also
      studied in vitro expression of PrP(c) in the Schwann cell line MSC-80 and
      demonstrated that it expresses PrP(c) at the same location. More specifically, we
      demonstrated that this glial cell line, when infected in vitro with the mouse
      Chandler prion strain, both produces the PrP(Sc) till after 18 passages and is
      able to transmit disease to mice, which then develop the typical signs of prion
      diseases. It is the first time that infection and replication of PrP(Sc) are
      shown in a peripheral glial cell line.

PMID- 11836422
TI  - De novo infection and serial transmission of Kaposi's sarcoma-associated
      herpesvirus in cultured endothelial cells.
AB  - Infection by Kaposi's sarcoma-associated herpesvirus (KSHV) is central to the
      pathogenesis of the endothelial neoplasm Kaposi's sarcoma (KS) and is also linked
      to the rare B-cell tumor known as primary effusion lymphoma (PEL). Latently
      infected PEL cell lines can be induced to enter the lytic cycle and produce KSHV
      virions. However, such cells do not support de novo infection or serial
      propagation of KSHV. These limitations have prevented the development of systems
      for the genetic analysis of KSHV and have impeded a deeper understanding of KS
      pathogenesis. Here we show that human dermal microvascular endothelial cells
      immortalized by expression of telomerase can be readily infected by KSHV virions
      produced by PEL cells. Infection is predominantly latent, but a small
      subpopulation enters the lytic cycle spontaneously. Phorbol ester (tetradecanoyl
      phorbol acetate [TPA]) treatment of latently infected cells leads to enhanced
      induction of lytic KSHV replication, resulting in foci of cytopathic effect.
      There is no cytopathic effect or viral DNA expansion when infected TIME cells
      (telomerase-immortalized microvascular endothelial cells) are TPA induced in the
      presence of phosphonoacetic acid (PAA), an inhibitor of herpesvirus replication.
      Supernatants from phorbol-induced cultures transfer latent KSHV infection to
      uninfected cells, which can likewise be induced to undergo lytic replication by
      TPA treatment, and the virus can be further serially transmitted. Serial passage
      of the virus in TIME cells is completely inhibited when TPA treatment is done in
      the presence of PAA. Latently infected endothelial cells do not undergo major
      morphological changes or growth transformation, and infection is lost from the
      culture upon serial passage. This behavior faithfully recapitulates the behavior
      of spindle cells explanted from primary KS biopsies, strongly supporting the
      biological relevance of this culture system. These findings suggest that either
      the stability or the growth-deregulatory potential of the KSHV latency program in
      endothelial cells is more limited than might be predicted by analogy with other
      oncogenic viruses.

PMID- 11836423
TI  - Neurons differentially activate the herpes simplex virus type 1 immediate-early
      gene ICP0 and ICP27 promoters in transgenic mice.
AB  - Herpes simplex virus type 1 (HSV-1) immediate-early (IE) proteins are required
      for the expression of viral early and late proteins. It has been hypothesized
      that host neuronal proteins regulate expression of HSV-1 IE genes that in turn
      control viral latency and reactivation. We investigated the ability of neuronal
      proteins in vivo to activate HSV-1 IE gene promoters (ICP0 and ICP27) and a late
      gene promoter (gC). Transgenic mice containing IE (ICP0 and ICP27) and late (gC)
      gene promoters of HSV-1 fused to the Escherichia coli beta-galactosidase coding
      sequence were generated. Expression of the ICP0 and ICP27 reporter transgenes was
      present in anatomically distinct subsets of neurons in the absence of viral
      proteins. The anatomic locations of beta-galactosidase-positive neurons in the
      brains of ICP0 and ICP27 reporter transgenic mice were similar and included
      cerebral cortex, lateral septal nucleus, cingulum, hippocampus, thalamus,
      amygdala, and vestibular nucleus. Trigeminal ganglion neurons were positive for
      beta-galactosidase in adult ICP0 and ICP27 reporter transgenic mice. The ICP0
      reporter transgene was differentially regulated in trigeminal ganglion neurons
      depending upon age. beta-galactosidase-labeled cells in trigeminal ganglia and
      cerebral cortex of ICP0 and ICP27 reporter transgenic mice were confirmed as
      neurons by double labeling with antineurofilament antibody. Nearly all
      nonneuronal cells in ICP0 and ICP27 reporter transgenic mice and all neuronal and
      nonneuronal cells in gC reporter transgenic mice were negative for beta
      galactosidase labeling in the absence of HSV-1. We conclude that factors in
      neurons are able to differentially regulate the HSV-1 IE gene promoters (ICP0 and
      ICP27) in transgenic mice in the absence of viral proteins. These findings are
      important for understanding the regulation of the latent and reactivated stages
      of HSV-1 infection in neurons.

PMID- 11836424
TI  - The human cytomegalovirus UL35 gene encodes two proteins with different
      functions.
AB  - The human cytomegalovirus (HCMV) virion is a complex structure that contains at
      least 30 proteins, many of which have been identified. We determined that the
      HCMV UL35 gene encodes two proteins, including a previously unidentified virion
      protein. A 22-kDa phosphoprotein (ppUL35(A)) was translated from a 1.2-kb UL35
      transcript by 4 h postinfection; a second phosphoprotein of 75 kDa (ppUL35) was
      translated from a 2.2-kb transcript predominantly late in infection. The 22-kDa
      protein localized to the nucleus, while the 75-kDa protein localized to the
      juxtanuclear compartment and was packaged into virion particles. The 22-kDa
      protein was identical to the COOH-terminal end of the 75-kDa protein but was not
      found in virions, thus defining the NH(2)-terminal portion of the 75-kDa protein
      as essential for packaging. Expression of the 22-kDa protein inhibited activation
      of the major immediate-early promoter by ppUL82 (pp71), suggesting that the UL35
      22-kDa protein may modulate expression of the major immediate-early gene.

PMID- 11836425
TI  - Epstein-Barr virus BALF1 is a BCL-2-like antagonist of the herpesvirus
      antiapoptotic BCL-2 proteins.
AB  - Cellular BCL-2 family proteins can inhibit or induce programmed cell death in
      part by counteracting the activity of other BCL-2 family members. All sequenced
      gammaherpesviruses encode a BCL-2 homologue that potently inhibits apoptosis and
      apparently escapes some of the regulatory mechanisms that govern the functions of
      their cellular counterparts. Examples of these protective proteins include BHRF1
      of Epstein-Barr virus (EBV) and KSBcl-2 of Kaposi's sarcoma-associated
      herpesvirus, also known as human herpesvirus 8. The gamma-1 subgroup of these
      viruses, such as EBV, encodes a second BCL-2 homologue. We have now found that
      this second BCL-2 homologue encoded by EBV, BALF1, inhibits the antiapoptotic
      activity of EBV BHRF1 and of KSBcl-2 in several transfected cell lines. However,
      BALF1 failed to inhibit the cellular BCL-2 family member, BCL-x(L). Thus, BALF1
      acts as a negative regulator of the survival function of BHRF1, similar to the
      counterbalance observed between cellular BCL-2 family members. Unlike the
      cellular BCL-2 family antagonists, BALF1 lacked proapoptotic activity and could
      not be converted into a proapoptotic factor in a manner similar to cellular BCL-2
      proteins by caspase cleavage or truncation of the N terminus.
      Coimmunoprecipitation experiments and immunofluorescence assays suggest that a
      minimal amount, if any, of the BHRF1 and BALF1 proteins colocalizes inside cells,
      suggesting that mechanisms other than direct interaction explain the suppressive
      function of BALF1.

PMID- 11836426
TI  - Separation of the DNA replication, segregation, and transcriptional activation
      functions of Epstein-Barr nuclear antigen 1.
AB  - In latent Epstein-Barr virus infection, the viral EBNA1 protein binds to specific
      sites in the viral origin of DNA replication, oriP, to activate the initiation of
      DNA replication, enhance the expression of other viral latency proteins, and
      partition the viral episomes during cell division. The DNA binding domain of
      EBNA1 is required for all three function, and a Gly-Arg-rich sequence between
      amino acids 325 and 376 is required for both the transcriptional activation and
      partitioning functions. We have used mutational analysis to identify additional
      EBNA1 sequences that contribute to EBNA1 functions. We show that EBNA1 amino
      acids 8 to 67 contribute to, but are not absolutely required for, EBNA1
      replication, partitioning, and transcriptional activation functions. A Gly-Arg
      rich sequence (amino acids 33 to 53) that is similar to that of amino acids 325
      to 376 and lies within the 8-to-67 region was not responsible for the functional
      contributions of residues 8 to 67, since deletion of amino acids 34 to 52 alone
      did not affect EBNA1 functions. We also found that deletion of amino acids 61 to
      83 eliminated the transcriptional activity of EBNA1 without affecting
      partitioning. This mutant also exhibited an increased replication efficiency that
      resulted in the maintenance of oriP plasmids at a copy number approximately
      fourfold higher than for wild-type EBNA1. The results indicate that the three
      EBNA1 functions have overlapping but different sequence requirements.
      Transcriptional activation requires residues 61 to 83 and 325 to 376 and is
      stimulated by residues 8 to 67; partitioning requires residues 325 to 376 and is
      stimulated by residues 8 to 67; and replication involves redundant contributions
      of both the 325-to-376 and 8-to-67 regions.

PMID- 11836427
TI  - Complete inhibition of tobamovirus multiplication by simultaneous mutations in
      two homologous host genes.
AB  - The TOM1 gene of Arabidopsis thaliana encodes a putative multipass transmembrane
      protein which is necessary for the efficient multiplication of tobamoviruses. We
      have previously shown that mutations severely destructive to the TOM1 gene reduce
      tobamovirus multiplication to low levels but do not impair it completely. In this
      report, we subjected one of the tom1 mutants (tom1-1) to another round of
      mutagenesis and isolated a new mutant which did not permit a detectable level of
      tobamovirus multiplication. In addition to tom1-1, this mutant carried a mutation
      referred to as tom3-1. Positional cloning showed that TOM3 was one of two TOM1
      like genes in Arabidopsis. Based on the similarity between the amino acid
      sequences of TOM1 and TOM3, together with the results of a Sos recruitment assay
      suggesting that both TOM1 and TOM3 bind tobamovirus-encoded replication proteins,
      we propose that TOM1 and TOM3 play parallel and essential roles in the
      replication of tobamoviruses.

PMID- 11836428
TI  - PrP(c) expression influences the establishment of herpes simplex virus type 1
      latency.
AB  - PrP(c) is a glycophosphatidylinositol-linked cell-surface protein expressed
      principally by neural tissue. The normal function of this protein is
      unestablished, although a role in either transmembrane signaling, cell-cell
      adhesion, or copper metabolism has been proposed. In this study we have
      investigated the effect of the neurotropic virus herpes simplex virus type 1 (HSV
      1) in strains of mice which express different levels of PrP(c). Viral gene
      expression under the control of the HSV-1 early promoter IE110, detected either
      by in situ hybridization for RNA transcripts or by beta-galactosidase (beta-Gal)
      activity from an inserted lacZ gene, showed that the magnitude of HSV replication
      was retarded in PrP-/- mice. This was reflected in the lower level of acute viral
      titers in tissues from these virus-inoculated mice. However, HSV-inoculated PrP-/
      mice contained higher levels of latent virus in both peripheral and central
      nervous tissue than those seen in mice which express PrP(c). Our observations
      show that lack of PrP(c) expression favors the establishment of HSV latency
      whereas HSV replication proceeds more efficiently in neuronal tissue that
      expresses this protein. The data further suggest that PrP(c) may be involved in a
      metabolic pathway that culminates in apoptosis of neurons that have been infected
      by neurotropic viruses.

PMID- 11836429
TI  - Chronic subclinical prion disease induced by low-dose inoculum.
AB  - We have compared the transmission characteristics of the two mouse-adapted
      scrapie isolates, ME7 and Rocky Mountain Laboratory (RML), in tga20 mice. These
      mice express elevated levels of PrP protein compared to wild-type mice and
      display a relatively short disease incubation period following intracerebral
      prion inoculation. Terminal prion disease in tga20 mice induced by ME7 or RML was
      characterized by a distinct pattern of clinical signs and different incubation
      times. High-dose RML inoculated intracerebrally into tga20 mice induced the most
      rapid onset of clinical signs, with mice succumbing to terminal disease after
      only 58 +/- 3 days. In contrast, high-dose ME7 gave a mean time to terminal
      disease of 74 +/- 0 days. Histological examination of brain sections from prion
      inoculated tga20 mice at terminal disease showed that ME7 gave rise to a more
      general and extensive pattern of vacuolation than RML. Low-dose inoculum failed
      to induce terminal disease but did cause preclinical symptoms, including the
      appearance of reversible clinical signs. Some mice oscillated between showing no
      clinical signs and early clinical signs for many months but never progressed to
      terminal disease. Brain tissue from these mice with chronic subclinical prion
      disease, sacrificed at >200 days postinoculation, contained high levels of
      infectivity and showed the presence of PrP(Sc). Parallel analysis of brain tissue
      from mice with terminal disease showed similar levels of infectivity and
      detectable PrP(Sc). These results show that high levels of infectivity and the
      presence of the abnormal isomer of PrP can be detected in mice with subclinical
      disease following low-dose prion inoculation.

PMID- 11836430
TI  - Ebola virus glycoproteins induce global surface protein down-modulation and loss
      of cell adherence.
AB  - The Ebola virus envelope glycoprotein (GP) derived from the pathogenic Zaire
      subtype mediates cell rounding and detachment from the extracellular matrix in
      293T cells. In this study we provide evidence that GPs from the other pathogenic
      subtypes, Sudan and Cote d'Ivoire, as well as from Reston, a strain thought to be
      nonpathogenic in humans, also induced cell rounding, albeit at lower levels than
      Zaire GP. Sequential removal of regions of potential O-linked glycosylation at
      the C terminus of GP1 led to a step-wise reduction in cell detachment without
      obviously affecting GP function, suggesting that such modifications are involved
      in inducing the detachment phenotype. While causing cell rounding and detachment
      in 293T cells, Ebola virus GP did not cause an increase in cell death. Indeed,
      following transient expression of GP, cells were able to readhere and continue to
      divide. Also, the rounding effect was not limited to 293T cells. Replication
      deficient adenovirus vectors expressing Ebola virus GP induced the loss of cell
      adhesion in a range of cell lines and primary cell types, including those with
      proposed relevance to Ebola virus infection in vivo, such as endothelial cells
      and macrophages. In both transfected 293T and adenovirus-infected Vero cells, a
      reduction in cell surface expression of adhesion molecules such as integrin beta1
      concurrent with the loss of cell adhesion was observed. A number of other cell
      surface molecules, however, including major histocompatibility complex class I
      and the epidermal growth factor receptor, were also down-modulated, suggesting a
      global mechanism for surface molecule down-regulation.

PMID- 11836432
TI  - Identification of a type 1 peroxisomal targeting signal in a viral protein and
      demonstration of its targeting to the organelle.
AB  - Peroxisomes are unimembrane, respiratory organelles of the cell. Transport of
      cellular proteins to the peroxisomal matrix requires a type 1 peroxisomal
      targeting signal (PTS1) which essentially constitutes a tripeptide from the
      consensus sequence S/T/A/G/C/N-K/R/H-L/I/V/M/A/F/Y. Although PTS-containing
      proteins have been identified in eukaryotes, prokaryotes, and parasites, viral
      proteins with such signals have not been identified so far. We report here the
      first instance of a virus, the rotavirus, which causes infantile diarrhea
      worldwide, containing a functional C-terminal PTS1 in one of its proteins (VP4).
      Analysis of 153 rotavirus VP4-deduced amino acid sequences identified five groups
      of conserved C-terminal PTS1 tripeptide sequences (SKL, CKL, GKL, CRL, and CRI),
      of which CRL is represented in approximately 62% of the sequences. Infection of
      cells by a CRL-containing representative rotavirus (SA11 strain) and confocal
      immunofluorescence analysis revealed colocalization of VP4 with peroxisomal
      markers and morphological changes of peroxisomes. Further, transient cellular
      expression of green fluorescent protein (GFP)-fused VP4CRL resulted in transport
      of VP4 to peroxisomes, whereas the chimera lacking the PTS1 signal, GFP
      VP4DeltaCRL, resulted in diffuse cytoplasmic staining, suggesting a CRL-dependent
      targeting of the protein. The present study therefore demonstrates hitherto
      unreported organelle involvement, specifically of the peroxisomes, in rotaviral
      infections as demonstrated by using the SA11 strain of rotavirus and opens a new
      line of investigation toward understanding viral pathogenesis and disease
      mechanisms.

PMID- 11836433
TI  - Abrogation of Ref1 retrovirus restriction in human cells.
AB  - We have previously described postentry restriction of murine leukemia virus in
      mammals. Here we characterize the block in human cells. Restricted infection
      kinetics are multiple hit at high virus dose, and restriction is abrogated by
      preexposure to restricted virus. We hypothesize that restricted capsid can
      titrate out the restriction factor.

PMID- 11836434
TI  - Differential expression of viral Bcl-2 encoded by Kaposi's sarcoma-associated
      herpesvirus and human Bcl-2 in primary effusion lymphoma cells and Kaposi's
      sarcoma lesions.
AB  - Expression of human herpesvirus 8 viral Bcl-2 protein was demonstrated in spindle
      cells of late-stage Kaposi's sarcoma lesions but not in primary effusion lymphoma
      cell lines. In contrast, strong expression of human Bcl-2 was found in stimulated
      primary effusion lymphoma cells, whereas in Kaposi's sarcoma lesions preferential
      mononuclear cells, and to a lesser extent spindle cells, stained positive.

PMID- 11836431
TI  - Translation of polioviral mRNA is inhibited by cleavage of polypyrimidine tract
      binding proteins executed by polioviral 3C(pro).
AB  - The translation of polioviral mRNA occurs through an internal ribosomal entry
      site (IRES). Several RNA-binding proteins, such as polypyrimidine tract-binding
      protein (PTB) and poly(rC)-binding protein (PCBP), are required for the
      poliovirus IRES-dependent translation. Here we report that a poliovirus protein,
      3C(pro) (and/or 3CD(pro)), cleaves PTB isoforms (PTB1, PTB2, and PTB4). Three
      3C(pro) target sites (one major target site and two minor target sites) exist in
      PTBs. PTB fragments generated by poliovirus infection are redistributed to the
      cytoplasm from the nucleus, where most of the intact PTBs are localized.
      Moreover, these PTB fragments inhibit polioviral IRES-dependent translation in a
      cell-based assay system. We speculate that the proteolytic cleavage of PTBs may
      contribute to the molecular switching from translation to replication of
      polioviral RNA.

PMID- 11836435
TI  - Mutant tax protein from bovine leukemia virus with enhanced ability to activate
      the expression of c-fos.
AB  - Bovine leukemia virus (BLV) is the etiologic agent of enzootic bovine leukosis.
      We previously identified several mutants of the BLV Tax protein with an ability
      to transactivate transcription via the BLV enhancer that is significantly greater
      than that of the wild-type Tax protein. Moreover, the mutant proteins also
      activated other viral enhancers, such as the enhancer of human T-cell leukemia
      virus type 1, which cannot be activated by wild-type BLV Tax. In this study, we
      demonstrated that the mutant proteins but not wild-type protein activate the
      upstream sequence of the human c-fos gene, which contains two major cis-acting
      elements, the CArG box and cyclic AMP-responsive element (CRE) motif. The mutant
      protein also strongly increased levels of endogenous c-fos mRNA in both human and
      bovine cell lines. On the other hand, the wild-type Tax protein has no activity
      to activate the expression of human c-fos, indicating that wild-type BLV Tax
      might discriminate between human and bovine c-fos promoter sequences. Deletion
      and point-mutational analysis of the cis-acting elements revealed that both the
      CArG box and the CRE motif were indispensable for the activation of c-fos by the
      mutant BLV Tax protein. Our results suggest that the mutant BLV Tax proteins
      might not only have the ability to enhance the production of virus particles but
      might also have increased ability to induce leukemia.

PMID- 11836436
TI  - B7 costimulation plays an important role in protection from herpes simplex virus
      type 2-mediated pathology.
AB  - We have used mice lacking both B7-1 and B7-2 costimulation molecules (B7KO) to
      investigate the effects of B7 costimulation on herpes simplex virus type 2 (HSV
      2) pathogenesis. B7KO mice infected intravaginally with virulent HSV-2 showed
      more severe genital and neurologic disease and higher mortality rates than their
      wild-type counterparts. These results suggest that B7 costimulation molecules
      play an important role in the development of primary immune responses protective
      against HSV-2.

PMID- 11836437
TI  - Sequence variation in a newly identified HLA-B35-restricted epitope in the
      influenza A virus nucleoprotein associated with escape from cytotoxic T
      lymphocytes.
AB  - Here, we describe a new HLA-B*3501-restricted cytotoxic T lymphocyte (CTL)
      epitope in the influenza A virus (H3N2) nucleoprotein, which was found to exhibit
      a high degree of variation at nonanchor residues. The influenza virus variants
      emerged in chronological order, and CTLs directed against old variants failed to
      recognize more recent strains of influenza A virus, indicating an escape from CTL
      immunity.

PMID- 11836438
TI  - Contribution of peaks of virus load to simian immunodeficiency virus
      pathogenesis.
AB  - The mechanisms causing AIDS and subsequently death in human immunodeficiency
      virus type 1 infection are not yet fully understood. Nonetheless, correlates of
      accelerated progression to disease based on immunological and virological markers
      have been identified. The best correlate identified to date is the baseline virus
      load or the so-called viral set point. By focusing on a virus load measurement
      from a restricted time range, however, we ignore valuable information contained
      in the long-term profile of the virus load. Here, we investigate the relationship
      between virus load and survival with the aid of a statistical model. The model
      takes into consideration the virus load at every stage of the disease. In
      particular, we aim to determine the effect of peaks of virus load on disease
      progression. We fit our model to unique sequential viral load data of 12 simian
      immunodeficiency virus mac251-infected rhesus macaques which contain frequent
      measurements throughout the entire course of the infection until the development
      of simian AIDS. Our model enables us to predict the survival times of the animals
      more accurately than an equivalent model which considers the viral set point
      only. Furthermore, we find that peaks of the virus load contribute less to
      disease progression than phases of low virus load with the same amount of viral
      turnover. Our analysis implies that the total viral turnover is not the best
      correlate of survival. As a consequence, the direct cytopathic effects of virus
      replication may, by themselves, have less of an impact on disease progression
      than previously thought.

PMID- 11836439
TI  - Enhancement of hepatitis B virus replication by its X protein in transgenic mice.
AB  - Hepatitis B virus (HBV) X gene encodes a multifunctional protein that can
      regulate cellular signaling pathways, interact with cellular transcription
      factors, and induce hepatocellular oncogenesis. In spite of its diverse
      activities, the precise role of the X protein in the viral life cycle of HBV
      remains unclear. To investigate this question, we have produced transgenic mice
      that carry either the wild-type HBV genome or a mutated HBV genome incapable of
      expressing the 16.5-kDa X protein. Our results indicate that while the X protein
      is not absolutely essential for HBV replication or its maturation in transgenic
      mice, it can enhance viral replication, apparently by activating viral gene
      expression. These results demonstrate a transactivation role of the X protein in
      HBV replication in transgenic mice.

PMID- 11836442
TI  - Postmodern cancer: the role of human immunodeficiency virus in uterine cervical
      cancer.
AB  - The association between cervical cancer and human papillomavirus (HPV) is well
      known, but its association with human immunodeficiency virus (HIV) is
      controversial. Coinfection with HPV and HIV is to be expected and recent
      epidemiological data from Africa show that cervical cancer is the most common
      AIDS defining neoplasm in women. Unlike other AIDS defining neoplasms, the
      occurrence of cervical cancer is not dependent on immune compromise. HIV alters
      the natural history of HPV infection, with decreased regression rates and more
      rapid progression to high grade and invasive lesions, which are refractory to
      treatment, requiring more stringent intervention and monitoring. The more
      aggressive behaviour is mirrored by a different molecular pathway. HIV associated
      cervical cancers are thought to progress through the microsatellite instability
      pathway, whereas HIV negative ones progress through loss of heterozygosity.
      Interaction is probably via viral proteins, with HIV proteins enhancing
      effectiveness of HPV proteins, and perhaps contributing to cell cycle disruption.
      Dysregulation of the cellular and humoral arms of the local and systemic immune
      systems may ensure disease progression. Furthermore, HPV infection may predispose
      to HIV infection and facilitate its progression.

PMID- 11836443
TI  - Methods of molecular analysis: assessing losses and gains in tumours.
AB  - The study of chromosomal aberrations has facilitated the understanding of
      tumorigenesis. By applying molecular genetic techniques to regions highlighted by
      cytogenetic study, many genes important in tumorigenesis have been identified.
      This review will describe the cytogenetic and molecular cytogenetic techniques
      used to identify these changes. The clinical information that they can provide,
      including diagnostic and prognostic information, will also briefly be discussed.

PMID- 11836444
TI  - Association of the D allele of the angiotensin I converting enzyme polymorphism
      with malignant vascular injury.
AB  - AIMS: To determine whether there is an association between the insertion/deletion
      (I/D) polymorphism of the human angiotensin I converting enzyme (ACE) gene and
      malignant vascular injury (MVI). METHODS: The polymerase chain reaction was used
      to genotype DNA extracted from archival, paraffin wax embedded renal biopsy
      material from 48 patients with MVI, made up from cases of malignant hypertension
      (n = 23), scleroderma (n = 10), and haemolytic uraemic syndrome (n = 15), and
      from whole blood samples from 191 healthy controls. RESULTS: The D allele was
      found more frequently in cases of MVI than in healthy controls, (65% v 52%). Both
      the DD and I/D genotypes occurred significantly more frequently in patients with
      MVI than did the II genotype (chi(2) = 7.26, p = 0.007; and chi(2) = 4.06, p =
      0.04, respectively). CONCLUSIONS: Possession of at least one copy of the D allele
      is associated with an increased risk of developing MVI. Our data support a
      dominant mode of effect for the D allele. Use of the I/D polymorphism as a
      genetic marker for MVI may be of value clinically in identifying at risk
      individuals before the development of target end organ damage. Furthermore, those
      at risk may benefit from early ACE inhibition.

PMID- 11836440
TI  - Haemophilia A and haemophilia B: molecular insights.
AB  - This review focuses on selected areas that should interest both the scientist and
      the clinician alike: polymorphisms within the factor VIII and factor IX genes,
      their linkage, and their ethnic variation; a general assessment of mutations
      within both genes and a detailed inspection of the molecular pathology of certain
      mutations to illustrate the diverse cause-effect relations that exist; a summary
      of current knowledge on molecular aspects of inhibitor production; and an
      introduction to the new areas of factor VIII and factor IX catabolism. An
      appendix defining various terms encountered in the molecular genetics of the
      haemophilias is included, together with an appendix providing accession numbers
      and locus identification links for accessing gene and sequence information in the
      international nucleic acid databases.

PMID- 11836445
TI  - Detection of genes expressed in primary colon cancers by in situ hybridisation:
      overexpression of RACK 1.
AB  - AIMS: The isolation of various genes that are expressed in a region specific
      manner is considered useful for research in molecular pathology. In situ
      hybridisation (ISH) was used in a screening procedure to isolate these genes
      efficiently, using colon cancer as a model. METHODS: Suppression subtractive
      hybridisation (SSH) between colon cancer tissue samples and corresponding non
      cancerous tissues was performed. Genes showing high expression in the cancers
      were selected using macro-DNA array analysis. As a final screening procedure,
      conventional ISH was performed to isolate genes expressed specifically in colon
      cancers. RESULTS: Sixty nine clones were selected by SSH and macro-DNA array
      analyses. These clones were then analysed by ISH to examine their expression
      patterns. ISH screening revealed that all the clones screened showed more intense
      signals in colon cancers than in non-cancerous tissues. Among them, RACK 1, which
      is a protein kinase C receptor and a homologue of the G protein beta subunit, was
      expressed intensely in colon cancer cells. RACK 1 expression was evaluated in
      multiple samples by ISH, and the results confirmed that RACK 1 was universally
      overexpressed in cells of all 11 colon cancers examined. CONCLUSIONS: Many genes,
      including RACK 1, expressed in colon cancer cells can be isolated efficiently by
      this method, and their precise expression pattern can be evaluated. These results
      indicate that ISH is an excellent technique for systemic screening of genes
      expressed in a region specific manner.

PMID- 11836446
TI  - Expression of components of the IGF signalling system in childhood acute
      lymphoblastic leukaemia.
AB  - BACKGROUND: Alterations in the insulin-like growth factor (IGF) system have been
      reported for different tumours. They are of particular interest in the search for
      new prognostic and therapeutic approaches in cancer. In childhood acute
      lymphoblastic leukaemia (ALL) the amount of "tumour mass" at diagnosis can exceed
      1 kg. To understand the endocrine, paracrine, and autocrine potential of the
      malignant transformed progenitor cells, the ability of these cells to express
      components of the IGF system needs to be investigated. AIM: To characterise the
      expression pattern of genes of the IGF system in malignant lymphoblasts of
      children suffering from ALL. METHODS: Reverse transcription polymerase chain
      reaction of Ficoll separated mononuclear cells from 142 children with ALL, 127
      cord blood samples, and 55 blood samples of age matched controls were studied.
      RESULTS: The expression of IGF-I, IGF-II, IGF binding protein 5 (IGFBP-5), and
      CTGF (IGFBP-rP2) was seen in a higher proportion of mononuclear cells of patients
      with ALL than in controls. Patients with ALL who were in continuous remission had
      a lower percentage of IGFBP-2 and IGFBP-3 expressing mononuclear cells at
      diagnosis than did those who developed a relapse. Only malignant lymphoblasts of
      B cell origin showed expression of CTGF (IGFBP-rP2). Malignant lymphoblasts of T
      cell origin more often expressed IGFBP-2 and IGFBP-5, whereas IGF-II and IGFBP-3
      expression was seen more often in lymphoblasts of B cell origin. CONCLUSIONS:
      Malignant lymphoblasts of patients with ALL express components of the IGF system
      and therefore promote their own growth in an autocrine, paracrine, or endocrine
      manner. Whether these components will be useful as prognostic factors in the
      stratification of ALL treatment in children needs to be evaluated.

PMID- 11836447
TI  - Identification of an IGF-1R kinase regulatory phosphatase using the fission yeast
      Schizosaccharomyces pombe and a GFP tagged IGF-1R in mammalian cells.
AB  - AIMS: To study the regulation of type 1 insulin like growth factor receptor (IGF
      1R) tyrosine kinase activity using the fission yeast Schizosaccharomyces pombe
      and a green fluorescent protein (GFP) tagged, full length IGF-1R. METHODS: The
      beta chain of the IGF-1R (betawt) was expressed under inducible conditions in the
      fission yeast S. pombe. Western blot analysis with antiphosphotyrosine antibodies
      was used to assess the kinase activity of betawt. A GFP tagged IGF-1R (GFP-IGF
      1R) was constructed to study the tyrosine kinase activity of the full length IGF
      1R. The signalling capabilities of GFP-IGF-1R in response to IGF-1 stimulation
      were investigated in transiently transfected fibroblasts. Immunofluorescent
      staining for cellular phosphotyrosine content was used to assess the localisation
      and tyrosine kinase activity of GFP-IGF-1R. RESULTS: The betawt protein displayed
      functional tyrosine kinase activity in S pombe and phosphorylated endogenous
      yeast proteins. In response to IGF-1 stimulation, the GFP-IGF-1R became
      autophosphorylated and also activated the phosphatidylinositol 3-kinase and
      mitogen activated protein kinase pathways. Tyrosine phosphorylation and kinase
      activity of the GFP-IGF-1R could be visualised by immunofluorescence with
      antiphosphotyrosine antibodies. Coexpression of a mammalian tyrosine phosphatase
      PTP1B with betawt completely inhibited this tyrosine kinase activity in yeast and
      also reduced the tyrosine phosphorylation in COS cells transfected with the GFP
      IGF-1R. CONCLUSIONS: Schizosaccharomyces pombe can be used to analyse the
      tyrosine kinase activity of the IGF-1R beta chain and its regulation by tyrosine
      phosphatases. In addition, the regulation of IGF-1R tyrosine kinase activity can
      be studied using a GFP tagged IGF-1R. Using both of these methods, IGF-1R kinase
      activity was shown to be inhibited by the protein tyrosine phosphatase, PTP1B.

PMID- 11836448
TI  - 7-Deaza-2'-deoxyguanosine allows PCR and sequencing reactions from CpG islands.
AB  - CpG islands are GC rich sequences that are found in the promoters of many genes
      in higher eukaryotes. They contain a high frequency of CG dinucleotides, which
      are substrates for DNA methylases. Methylation leads to transcriptional silencing
      of promoters. Owing to their high GC content CpG islands exhibit strong base-base
      interactions, which lead to superstructures and consequently to regions with
      higher melting temperatures. Therefore, Taq polymerases (especially sequenases)
      fall off their templates, causing premature termination of the polymerase chain
      reaction (PCR) or sequencing reactions. The results from such reactions are thus
      insufficient for further analysis. Therefore, we have evaluated the use of 7
      deaza-2'-deoxyguanosine for PCR amplification of the human p16(INK4A) promoter
      and sequencing of HUMARA exon 1 PCR products. Our results show that the addition
      of 7-deaza-2'-deoxyguanosine significantly improves results, particularly when
      small amounts of poor quality DNA are available as starting material.

PMID- 11836449
TI  - An R201H activating mutation of the GNAS1 (Gsalpha) gene in a corticotroph
      pituitary adenoma.
AB  - In the pituitary gland, activating mutations of the GNAS1 (Gsalpha) gene at
      Gln227 have been identified in adrenocorticotrophin secreting, growth hormone
      secreting, and prolactin secreting adenomas. To date, mutations at the codon
      encoding R201, typically underlying the McCune-Albright syndrome and isolated
      fibrous dysplasia of bone, have been demonstrated only in growth hormone
      secreting pituitary adenomas. In this study, a polymerase chain reaction
      amplified target sequence in exon 8 of the GNAS1 gene was sequenced, identifying
      the first R201 mutation seen in an isolated basophilic adenoma which generated
      Cushing's disease in a child. This case adds Cushing's disease to the range of
      human diseases caused by R201 mutations of the GNAS1 gene.

PMID- 11836450
TI  - Expression of glucocorticoid receptor and 11beta hydroxysteroid dehydrogenase in
      a case of pulmonary epithelioid haemangioendothelioma.
AB  - This report describes a case of pulmonary epithelioid haemangioendothelioma in
      which the tumour cells expressed the glucocorticoid receptor and 11beta
      hydroxysteroid dehydrogenase. The patient, a 15 year old girl, who had no other
      complaints or past illnesses, was found to have an abnormal shadow on a chest
      roentgenogram obtained at a school medical examination. Multiple nodular shadows
      in the bilateral lungs were also confirmed by computerised axial tomography scan.
      A diagnosis of pulmonary epithelioid haemangioendothelioma was made on the basis
      of lung biopsy specimens. The tumour cells were immunohistochemically positive
      for factor VIII related antigen, CD31, and CD34, but not surfactant apoprotein A.
      In addition, almost all of the tumour cells showed simultaneous expression of the
      glucocorticoid receptor and 11beta hydroxysteroid dehydrogenase, suggesting that
      steroid treatment would be effective.

PMID- 11836451
TI  - Fat mass measured by DXA varies with scan velocity.
AB  - OBJECTIVE: To study the influence of scan velocities of DXA on the measured size
      of fat mass, lean body mass, bone mineral content and density, and total body
      weight. RESEARCH METHODS AND PROCEDURES: The subjects were 71 healthy white
      adults, 38 women and 33 men. The mean age was 41.7 +/- 13.5 years and body mass
      index was 28.6 +/- 5.6 kg/m(2). The subjects were scanned consecutively in slow,
      medium, and fast scan mode by a Lunar DPX-IQ DXA scanner. RESULTS: Throughout the
      body mass index and sagittal height ranges, scanned lean body mass significantly
      decreased with higher scan velocity and lean body mass was 2.7% lower in fast
      than in medium mode (p < 0.0001). In contrast, fat mass, percentage of body fat,
      and bone mineral contents were higher with increasing scan velocity. Areas not
      analyzed by the scanner, so called blue spots, increased with scan velocity and
      sagittal height, and their presence significantly enhanced the error. Body weight
      estimated by DXA in slow mode was -0.8% lower than scale weight in the women (p <
      0.001) and -0.2% in men (not significant), and the difference was greater with
      increasing scan velocity. DISCUSSION: Scan velocity significantly influences the
      measured fat mass size, lean body mass, bone mineral content, and body weight. To
      obtain the most accurate results, slow mode is preferable and fast scans should
      be avoided. Future studies should report and take scan velocity into
      consideration.

PMID- 11836452
TI  - Long-term weight loss and breakfast in subjects in the National Weight Control
      Registry.
AB  - OBJECTIVE: To examine breakfast consumption in subjects maintaining a weight loss
      in the National Weight Control Registry (NWCR). RESEARCH METHODS AND PROCEDURES:
      A cross-sectional study in which 2959 subjects in the NWCR completed demographic
      and weight history questionnaires as well as questions about their current
      breakfast consumption. All subjects had maintained a weight loss of at least 13.6
      kg (30 lb) for at least 1 year; on average these subjects had lost 32 kg and kept
      it off for 6 years. RESULTS: A large proportion of NWCR subjects (2313 or 78%)
      reported regularly eating breakfast every day of the week. Only 114 subjects (4%)
      reported never eating breakfast. There was no difference in reported energy
      intake between breakfast eaters and non-eaters, but breakfast eaters reported
      slightly more physical activity than non-breakfast eaters (p = 0.05). DISCUSSION:
      Eating breakfast is a characteristic common to successful weight loss maintainers
      and may be a factor in their success.

PMID- 11836453
TI  - Obesity and long-term clinical and economic outcomes in coronary artery disease
      patients.
AB  - OBJECTIVE: Obesity is an important risk factor for coronary artery disease (CAD);
      however, its effect on acute coronary syndrome (ACS) patients' long-term clinical
      and economic outcomes has not been quantified. We assessed the impact of
      increasing body mass index (BMI) on 10-year outcomes for ACS patients. RESEARCH
      METHODS AND PROCEDURES: ACS patients with significant CAD receiving an initial
      cardiac catheterization at Duke University Medical Center between 1986 and 1997
      were included. Patients with a BMI < 18.5 kg/m(2) were excluded; the remaining
      patients were classified by BMI as normal, overweight, obese, or very obese.
      Medical costs were estimated from a prior ACS clinical trial with costs adjusted
      to 1997 dollars and discounted at 3% per annum. RESULTS: There were 9405 patients
      with data available for analysis. Follow-up was complete on >95% of patients.
      Patients who were obese at baseline increased from 20% to 33% between 1986 and
      1997. Increased BMI was associated with younger age, multi-morbidity, and less
      severe CAD at baseline. It was also associated with more clinical events, higher
      cumulative inpatient medical costs, and significant differences in unadjusted
      survival at 10 years. However, it was not associated with differences in 10-year
      survival after adjusting for baseline characteristic differences. DISCUSSION:
      Obese ACS patients are younger and are hospitalized more frequently during the
      first 10 years of their illness than are non-obese patients. They also incur
      higher cumulative inpatient medical costs, especially the very obese. These
      findings highlight the opportunities for therapeutic benefit that aggressive
      weight management and secondary prevention may provide this population.

PMID- 11836454
TI  - Vision and eating behavior.
AB  - OBJECTIVE: Eating behavior is influenced by internal and external factors. Vision
      is one part of the complex pattern of factors influencing the amount of food
      consumed during a meal. The aim of this study was to explore the impact of vision
      on the microstructure of eating behavior and the subjective motivation to eat.
      RESEARCH METHODS AND PROCEDURES: Nine blind subjects and nine matched seeing
      control subjects consumed a standardized meal registered by VIKTOR, an eating
      monitor, measuring the microstructure of the eating behavior. The eating behavior
      of the control subjects was registered twice, with and without blindfold.
      RESULTS: The eating behavior of the blind subjects did not differ from that of
      seeing control subjects. However, the eating behavior of seeing subjects eating
      with blindfold demonstrated a clear impact of vision on eating behavior. When
      blindfolded, subjects ate 22% less food (p < 0.05), had shorter meal durations (p
      < 0.05), and had less decelerated eating curves (p < 0.05). Despite a smaller
      amount of food consumed when blindfolded, the reported feeling of fullness was
      identical to that reported after the larger meal consumed without blindfold.
      DISCUSSION: The importance of vision in regulating our eating behavior is further
      stressed in this study. Eating with a blindfold decreased the intake of food,
      without making subjects feel less full. Eating blindfolded, therefore, may force
      subjects to rely more on internal signals. These results might be used as an aid
      in the development of new treatment strategies for obese subjects.

PMID- 11836456
TI  - Development and validation of the food-craving inventory.
AB  - OBJECTIVE: The primary aim of this study was to develop and validate the Food
      Craving Inventory (FCI), a self-report measure of specific food cravings.
      RESEARCH METHODS AND PROCEDURES: In a preliminary study, participants (n = 474)
      completed the initial version of the FCI. The results from this study were used
      in developing the revised FCI. Participants (n = 379) completed the revised FCI
      in the primary study designed to develop a self-report measure of specific food
      cravings. RESULTS: Common factor analysis yielded four conceptual factors
      (subscales) that were interpreted as high fats, sweets, carbohydrates/starches,
      and fast-food fats. Confirmatory factor analysis found that the four factors
      could be modeled as dimensions (or first-order factors) of a higher order
      construct-food craving. Test-retest and internal consistency analyses indicated
      good reliability for the total score and each of the subscales. Subscale scores
      were compared with scores on the Three Factor Eating Questionnaire and a
      conceptual measure of food craving. We found support for the content, concurrent,
      construct, and discriminant validity of the FCI. DISCUSSION: The FCI was found to
      be a reliable and valid measure of general and specific food cravings. The FCI
      can be used in research related to overeating and binge eating. Also, it may be
      useful in treatment studies that target obesity and/or food cravings.

PMID- 11836455
TI  - Ethnic comparison of weight loss in the Trial of Nonpharmacologic Interventions
      in the Elderly.
AB  - OBJECTIVE: To compare weight loss in blacks and whites in the Trial of
      Nonpharmacologic Interventions in the Elderly (TONE). RESEARCH METHODS AND
      PROCEDURES: TONE enrolled 421 overweight white and 164 overweight black adults,
      60 to 79 years old, with blood pressure well-controlled on a single,
      antihypertensive drug. Drug therapy withdrawal was attempted 3 months after
      randomization to counseling for weight loss, sodium reduction, both weight loss
      and sodium reduction, or to usual care, with follow-up for 15 to 36 months after
      enrollment. Statistical procedures included repeated measures analysis of
      covariance and logistic and proportional hazards regression. RESULTS: In the
      weight-loss condition, net weight change (in kilograms) was -2.7 in blacks and 
      5.9 in whites (p < 0.001; ethnic difference, p = 0.0002) at 6 months and -2.0 (p
      < 0.05) in blacks and -4.9 (p < 0.001) in whites at the end of follow-up (ethnic
      difference, p = 0.007). In weight/sodium, net weight change was -2.1 (p < 0.01)
      in blacks and -2.8 (p < 0.001) in whites at 6 months, and -1.9 in blacks and -1.7
      in whites at the end of follow-up (p < 0.05; ethnic difference, p > 0.5).
      Exploratory analyses suggested a more favorable pattern of weight change in
      blacks than in whites from 6 months onward. There was no ethnic difference in
      blood pressure outcomes. DISCUSSION: Whites lost more weight than blacks without,
      but not with, a concurrent focus on sodium reduction.

PMID- 11836457
TI  - The lean woman.
AB  - OBJECTIVE: In the current obesity epidemic, the ability to remain lean is
      beginning to be uncommon. Therefore, it was considered of interest to
      characterize such subjects. RESEARCH METHODS AND PROCEDURES: From a population of
      premenopausal women (n = 270), all 40 years of age, those with a similar body
      mass index (BMI) as women at the age of 21 years, born the same year (BMI = 21.1
      kg/m(2)) were selected among nonsmokers and compared with the remaining
      nonsmoking women. RESULTS: Lean women showed, as expected, low waist-to-hip
      circumference ratio and abdominal sagittal diameter as well as absence of other
      disease risk factors. Compared with the remaining women, 17 beta-estradiol was
      high and androgens were low, whereas insulin-like growth factor I and thyroid
      hormones showed no differences. Dihydroepiandrosterone sulfate was lower, whereas
      cortisol, measured in saliva repeatedly over a day, and adrenocorticotropin
      hormone were not different. Results from questionnaires indicated higher
      education and socioeconomic status, frequent sports activities, and better
      psychosocial adaptation and psychological health. A tetranucleotide repeat
      polymorphism in the fourth [corrected] intron of the aromatase P450 gene was
      longer among the lean (187 base pairs) than the rest of the women. Women with
      opposite phylogenetic characteristic have a short microsatellite (168 base pairs)
      in this gene locus. DISCUSSION: Lean, nonsmoking women enjoy an excellent health
      in not only anthropometric and metabolic factors, but also in neuroendocrine,
      endocrine, and psychological variables. The endocrine measurements suggest a well
      functioning aromatase, which in turn might have a genetic background,
      contributing to health. The aromatase gene might be important for regulation of
      body fat mass.

PMID- 11836458
TI  - Antibody-induced lysis of isolated rat epididymal adipocytes and complement
      activation in vivo.
AB  - OBJECTIVE: To identify human monoclonal antibodies selectively binding to human
      adipocytes and to evaluate their ability to induce lysis of isolated rat
      adipocytes in vitro and to reduce rat complement levels in vivo. RESEARCH METHODS
      AND PROCEDURES: Using phage display technology, human monoclonal antibodies
      binding to human adipocyte plasma membranes were identified. Three antibodies
      (Fat 13, Fat 37, and Fat 41) were selected based on their additional cross
      reaction with rat adipocytes and reformatted as a rat chimeric IgG2bs. The
      ability of these antibodies, both singly and in combination, to induce lysis of
      rat epididymal adipocytes in vitro and the reduction of serum complement levels
      in vivo in the rat was evaluated. RESULTS: All antibodies caused similar time-
      and dose-dependent lysis of isolated rat adipocytes. Calculated mean EC(50)
      values (maximum percentage of lysis in parentheses) were 0.680 microg/mL (63.2%),
      0.546 microg/mL (72.4%), and 0.391 microg/mL (73.7%) for Fat 13, Fat 37, and Fat
      41, respectively. Combinations were no more effective than individual antibodies
      in inducing lysis. Anti-adipocyte antibodies (both singly and in combination)
      were also similarly effective in vivo. In rats, doses of monoclonal antibody up
      to 10 mg/kg intraperitoneal generally caused almost complete depletion of serum
      complement up to 24 hours after dosing recovering to baseline values by day 5.
      DISCUSSION: Individual and combinations of monoclonal anti-adipocyte antibodies
      produced a complement-dependent and concentration-dependent activity to lyse
      adipocytes in vitro and in vivo as measured by a dramatic depletion in serum
      complement.

PMID- 11836459
TI  - Hypoxia inhibits leptin production by cultured rat adipocytes.

PMID- 11836461
TI  - Identifying populations at risk from environmental contamination from point
      sources.
AB  - OBJECTIVES: To compare methods for defining the population at risk from a point
      source of air pollution. A major challenge for environmental epidemiology lies in
      correctly identifying populations at risk from exposure to environmental
      pollutants. The complexity of today's environment makes it essential that the
      methods chosen are accurate and sensitive. METHODS: Environmental and
      mathematical methods were used to identify the population potentially exposed to
      a point source of airborne pollution emanating from a waste incinerator. Soil
      sampling was undertaken at 83 sites throughout the city and environs. The
      concentrations of arsenic and copper were measured at each site. Computer
      software produced smoothed contour plots of the distribution of arsenic and
      copper in the soil based on the information derived from the sampling sites. The
      population at risk was also identified using concentric rings of varying radii,
      with the source of pollution at the centre. Lastly, we used the sites that had
      previously been selected and measured the frequency of wind direction, speed and
      distance from the source of pollution at each site. Theoretical contour plots
      were constructed using the distance from the source of pollution at each site,
      with and without incorporating wind frequency as a function of direction.
      RESULTS: Each method identified different populations at risk from airborne
      pollution. The use of circles was a very imprecise way of identifying exposed
      populations. Mathematical modelling that incorporated wind direction was better.
      Soil sampling at many sites was accurate, as the method is direct; but it is very
      costly and the close proximity of high and low concentrations hindered
      interpretation. The smoothed contour plots derived from the soil sampling sites
      identified an exposed population that was similar to that derived from the spot
      sampling. CONCLUSIONS: Using circles as the only means of identifying the exposed
      population leads to dilution of the potential health effect. The best approach is
      to use local knowledge about wind direction and speed to estimate the population
      likely to be at risk; to back up this estimate by judicious use of soil sampling;
      to use contour mapping to guide the final selection of exposed and non-exposed
      populations; and finally, to interpret the populations identified as being at
      risk by incorporating information about other potential sources of pollution
      (past and present) in the area.

PMID- 11836462
TI  - Increase in interleukin-6 and fibrinogen after exposure to dust in tunnel
      construction workers.
AB  - OBJECTIVES: To see if there is any change in blood concentrations of interleukin
      6 (IL-6) and fibrinogen during a working shift in tunnel construction workers.
      METHODS: 12 Tunnel construction workers were followed up during a 24 hours period
      after returning from a 9 day work free period. The first blood sample was taken
      on Monday afternoon before starting the shift. Another was taken around midnight
      after 8 hours of work, and another the next afternoon after about 12 hours of
      rest. Exposure to respirable dust was measured by personal samplers. RESULTS: The
      exposure of the workers to respirable dust, in terms of an 8 hour time weighted
      average, varied between 0.3 and 1.9 mg/m(3). For IL-6, there was an increase in
      the median serum concentration from 1.14 ng/l before starting the shift to 4.86
      ng/l after 8 hours of work (p=0.002). For fibrinogen, there was an increase in
      the median concentration from 3.40 g/l before entering the shift to 3.70 g/l 24
      hours later (p=0.044). There was a positive correlation between values of IL-6 at
      the end of the working shift and the fibrinogen concentrations the next afternoon
      (Pearson's R=0.73, p=0.007). The observed increase in IL-6 was significant for
      both smokers and non-smokers. CONCLUSION: The study shows an increase in both IL
      6 and fibrinogen concentrations during a working shift for both smoking and non
      smoking tunnel construction workers.

PMID- 11836463
TI  - The risk to the United Kingdom population of zinc cadmium sulfide dispersion by
      the Ministry of Defence during the "cold war".
AB  - OBJECTIVES: To estimate exposures to cadmium (Cd) received by the United Kingdom
      population as a result of the dispersion of zinc Cd sulfide (ZnCdS) by the
      Ministry of Defence between 1953 and 1964, as a simulator of biological warfare
      agents. METHODS: A retrospective risk assessment study was carried out on the
      United Kingdom population during the period 1953-64. This determined land and air
      dispersion of ZnCdS over most of the United Kingdom, inhalation exposure of the
      United Kingdom population, soil contamination, and risks to personnel operating
      equipment that dispersed ZnCdS. RESULTS: About 4600 kg ZnCdS were dispersed from
      aircraft and ships, at times when the prevailing winds would allow large areas of
      the country to be covered. Cadmium released from 44 long range trials for which
      data are available, and extrapolated to a total of 76 trials to allow for trials
      with incomplete information, is about 1.2% of the estimated total release of Cd
      into the atmosphere over the same period. "Worst case" estimates are 10 microg Cd
      inhaled over 8 years, equivalent to Cd inhaled in an urban environment in 12100
      days, or from smoking 100 cigarettes. A further 250 kg ZnCdS was dispersed from
      the land based sites, but significant soil contamination occurred only in limited
      areas, which were and have remained uninhabited. Of the four personnel involved
      in the dispersion procedures (who were probably exposed to much higher
      concentrations of Cd than people on the ground), none are suspected of having
      related illnesses. CONCLUSION: Exposure to Cd from dissemination of ZnCdS during
      the "cold war" should not have resulted in adverse health effects in the United
      Kingdom population.

PMID- 11836464
TI  - Increased morbidity from nasopharyngeal carcinoma and chronic pharyngitis or
      sinusitis among workers at a newspaper printing company.
AB  - OBJECTIVES: To determine the association between printing works and nasopharygeal
      carcinoma as well as other diseases. METHODS: Demographic data were obtained for
      those who had worked in a particular newspaper company since its establishment in
      1950. Through access to the data bank of the hospital records of the Labor
      Insurance Bureau for 1985-94, all workers were identified who had been admitted
      to hospital during their employment in the newspaper company. Multiple logistic
      regressions were performed to estimate the adjusted morbidity odds ratio (OR) for
      various diseases among the printing workers with cardiovascular diseases as the
      reference diseases. Biopsy specimens from patients with nasopharyngeal carcinoma
      were all subjected to in situ hybridisation of Epstein-Barr virus (EBV), and
      colocalisation of EBV and secretor component protein. RESULTS: Of the 1564 people
      who had worked in this company, 579 of them were admitted to hospital at least
      once. Five out of 144 printing workers admitted to hospital were diagnosed with
      nasopharyngeal carcinoma compared with none of the other 435 non-printing workers
      admitted to hospital. The morbidity OR for nasopharyngeal carcinoma in printing
      workers was 57.0 (95% confidence interval (95% CI) 2.8 to 1155.3). The morbidity
      OR for benign skin tumours was 28.0 (95% CI 2.7 to 293.1). Chronic pharyngitis or
      sinusitis also showed significant relations with printing works with a morbidity
      OR 29.4 (95% CI 1.7 to 514.7). Using all other diseases as the reference diseases
      for calculation of morbidity ORs still showed a similar trend. In situ
      hybridisation of EBV encoded small nuclear RNA-1 (EBER-1) showed tumour cells
      free of the EBV in each biopsy specimen. Colocalisation of EBER-1 and secretor
      component showed that some tumour cells contained both secretor component and EBV
      signal in each case. CONCLUSION: Printing works are associated with an increased
      risk of nasopharyngeal carcinoma, benign skin tumours, chronic pharyngitis or
      sinusitis, chronic liver diseases, and mechanical injuries. Induction of the
      development of nasopharyngeal carcinoma is probably not related to EBV infection
      in these patients.

PMID- 11836465
TI  - Nasal patency is related to dust exposure in woodworkers.
AB  - OBJECTIVES: A cross sectional study of 54 furniture factories and three control
      factories was conducted to investigate the relation between subjective and
      objective nasal obstruction and exposure to wood dust. METHODS: Acoustic
      rhinometry was performed on 161 woodworkers and 19 controls. For each person,
      four measuring rounds were performed: before work, after 4 hours of work, and
      after 7 hours of work before and after decongestion. Before the first and third
      measuring round, each person rated the current feeling of nasal obstruction in
      the left and right nostril separately, using a visual analogue scale. Personal
      passive dust measurements were performed on 140 woodworkers. RESULTS: The mean
      (SD) of equivalent inhalable dust was relatively low, 1.17 (0.62) mg/m(3), range
      0.17-3.44 mg/m(3). The exposure was divided into four levels: controls, low
      exposure, medium exposure, and high exposure. For the two highest concentrations
      of exposure, a significant increase in congestion--decreased nasal cavity volume
      and cross sectional areas--was found after 4 and 7 hours of work, compared with
      before work. Multivariate linear regression analysis showed positive correlations
      between concentration of dust and change in mucosal swelling. A significant
      increase in self rated nasal obstruction was found after work compared with
      before work for the two highest exposure groups. No correlation between objective
      nasal variables and self rated nasal obstruction was found. CONCLUSION: Exposure
      to wood dust was related in a dose dependent manner to acute nasal obstruction
      measured by acoustic rhinometry and self reported obstruction, but no correlation
      was found between measured and self reported obstruction.

PMID- 11836466
TI  - Associations between daily mortalities from respiratory and cardiovascular
      diseases and air pollution in Hong Kong, China.
AB  - OBJECTIVE: To investigate the association between ambient concentrations of air
      pollutants and respiratory and cardiovascular mortalities in Hong Kong. METHODS:
      Retrospective ecological study. A Poisson regression of concentrations of daily
      air pollutants on daily mortalities for respiratory and cardiovascular diseases
      in Hong Kong from 1995 to the end of 1998 was performed using the air pollution
      and health: the European approach (APHEA) protocol. The effects of time trend,
      seasonal variations, temperature, and humidity were adjusted. Autocorrelation and
      overdispersion were corrected. Daily concentrations of nitrogen dioxide (NO2),
      sulphur dioxide (SO2), ozone (O3), and particulate matter <10 microm in
      aerodynamic diameter (PM10) were averaged from eight monitoring stations in Hong
      Kong. Relative risks (RRs) of respiratory and cardiovascular mortalities (per 10
      microg/m(3) increase in air pollutant concentration) were calculated. RESULTS:
      Significant associations were found between mortalities for all respiratory
      diseases and ischaemic heart diseases (IHD) and the concentrations of all
      pollutants when analysed singly. The RRs for all respiratory mortalities (for a
      10 microg/m(3) increase in the concentration of a pollutant) ranged from 1.008
      (for PM10) to 1.015 (for SO2) and were higher for chronic obstructive pulmonary
      diseases (COPD) with all pollutants except SO2, ranging from 1.017 (for PM10) to
      1.034 (for O3). RRs for IHD ranged from 1.009 (for O3) to 1.028 (for SO2). In a
      multipollutant model, O3 and SO2 were significantly associated with all
      respiratory mortalities, whereas NO2 was associated with mortality from IHD. No
      interactions were detected between any of the pollutants or with the winter
      season. A dose-response effect was evident for all air pollutants. Harvesting was
      not found in the short term. CONCLUSIONS: Mortality risks were detected at
      current ambient concentrations of air pollutants. The associations with the
      particulates and some gaseous pollutants when analysed singly were consistent
      with many reported in temperate countries. PM10 was not associated with
      respiratory or cardiovascular mortalities in multipollutant analyses.

PMID- 11836467
TI  - Exposure to crystalline silica, silicosis, and lung disease other than cancer in
      diatomaceous earth industry workers: a quantitative risk assessment.
AB  - OBJECTIVES: To estimate excess lifetime risk of (a) mortality from lung disease
      other than cancer (LDOC), and, (b) onset of radiographic silicosis, arising from
      occupational exposure to respirable crystalline silica dust. METHODS: Data from a
      cohort of California diatomaceous earth mining and processing workers exposed to
      crystalline silica dust (mainly as cristobalite) were reanalyzed with Poisson
      regression methods with internal and external adjustments for potential
      confounding by calendar time, age, smoking, Hispanic ethnicity, and time since
      first observation. Model fit was evaluated by comparing deviances and fitting
      cubic spline models. Lifetime risks of death from LDOC and radiographic silicosis
      were estimated up to age 85 with an actuarial approach accounting for competing
      causes of death. RESULTS: For deaths due to LDOC, a linear relative rate model
      gave the best fit in Poisson regression analyses. At the mean cumulative exposure
      of LDOC cases to silica, after adjustment for smoking, the estimated rate ratio
      was 4.2 (p<0.0001); at the maximum cumulative exposure of cases, the rate ratio
      was 18.4. The excess lifetime risk for white men exposed to respirable
      cristobalite dust for 45 years at the current permissible exposure limit (PEL;
      about 0.05 mg/m(3)) of the Occupational Safety and Health Administration was
      54/1000 (95% confidence interval (95% CI) 17 to 150). For 70 incident cases of
      radiographic silicosis largely manifest before the end of employment, the best
      fit was also the linear relative rate model, predicting a rate ratio of 25.6 for
      silicosis at the mean cumulative exposure of the cases (p<0.0001). The excess
      lifetime risk for silicosis at the current PEL was 75/1000. CONCLUSION: Current
      occupational health standards for crystalline silica permit risks of lung disease
      other than cancer far in excess of what is usually considered acceptable by the
      Occupational Safety and Health Administration (a lifetime risk of less than one
      in a thousand deaths).

PMID- 11836468
TI  - Decreased white blood cell counts in semiconductor manufacturing workers in
      Taiwan.
AB  - OBJECTIVES: To assess the systematic health effects on the liver, kidney, and
      haematological function tests of workers in semiconductors in Taiwan. METHODS:
      926 workers of a semiconductor plant in Taiwan in July 1995 were investigated.
      Complete blood tests including liver, kidney, and haematological functions were
      available from 227 workers. RESULTS: There was a significantly lower mean (SD)
      white blood cell (WBC) count in male workers of photolithography (5870
      (1190)/mm(3), p=0.003) and implantation (6190 (1150)/mm(3), p=0.018) than that of
      male control workers (7350 (1660)/mm(3)). There was a significantly higher
      prevalence of leukopenia in male photolithography workers (6 of 20; 30%) than in
      male control workers (1 of 18; 5.6%), the crude odds ratio (OR) was 7.3 (95%
      confidence interval (95% CI) 1 to 55.6), and the multivariate adjusted OR was 8.1
      (95% CI 0.83 to 78.3). The tests for serum glutamic oxaloacetic transaminase
      (SGOT), serum glutamic pyruvic transaminase (SGPT), gamma glutamyl transferase
      (RGT), and creatinine were not significant among male workers. Female workers in
      photolithography had abnormal SGPT and RGT of borderline significance, the
      multivariate adjusted ORs were 9.6 (95% CI 0.86 to 107) and 6.35 (95% CI 0.53 to
      75.8), respectively. CONCLUSIONS: This study suggests that leukopenia is a
      potential health effect in male fabrication workers of the semiconductor
      industry. The tasks of the process, maintenance, and equipment engineers which
      consisted mostly of men put them at risk for intermittent short term peak
      exposure to glycol ethers, ionising radiation, arsenic, or other toxins. The
      findings of this medical surveillance are significant; however, a further
      investigation of the aetiological factors and the subsequent health effects is
      necessary.

PMID- 11836470
TI  - Changes in rates and severity of compensation claims for asthma due to
      diisocyanates: a possible effect of medical surveillance measures.
AB  - OBJECTIVES: A medical surveillance programme was introduced into Ontario for
      workers exposed to diisocyanates in 1983, but no mandated surveillance programme
      is in effect in this province for other occupational respiratory sensitisers.
      This study assesses changes in incidence and severity of compensated claims for
      occupational asthma (OA) due to diisocyanates compared with other causes, which
      have occurred since the introduction of this surveillance programme. METHODS: New
      claims for OA compensated by the Ontario Workers' Compensation Board (WCB)
      between 1980 and 1993 were retrospectively reviewed. Linkage was made between
      these data and an Ontario Ministry of Health database to assess hospital
      admissions for asthma from the date of onset of OA until the end of 1996.
      RESULTS: Numbers of claims for OA induced by diisocyanates ranged from 9-15/year
      in 1980-83, increased up to 55-58 claims/year in 1988-90, then fell to 19-20
      claims/year by 1992-93. By contrast yearly numbers of claims for OA due to other
      causes increased up to 1985-87 then remained relatively stable. Duration of
      symptoms for OA induced by diisocyanates was shorter than for other claims and
      there were fewer hospital admissions among those with OA induced by diisocyanates
      than among those with OA induced by other causes. Occupational asthma from all
      causes was diagnosed earlier in claims for 1987-93 compared with 1980-86, and
      indicators of severity of asthma were also milder in accepted claims during 1987
      93 than in earlier claims. CONCLUSIONS: Although engineering and industrial
      hygiene measures may have contributed to these changes, our findings are also
      consistent with a beneficial contribution from the medical surveillance programme
      for workers exposed to diisocyanates.

PMID- 11836469
TI  - Influence of solvent exposure and aging on cognitive functioning: an 18 year
      follow up of formerly exposed floor layers and their controls.
AB  - OBJECTIVES: To extend our knowledge of how exposure to neurotoxic substances
      during working life affects cognitive functioning in the long term. Does long
      term occupational exposure to organic solvents lead to aggravated cognitive
      impairment later in life? METHODS: A follow up was conducted of floor layers
      exposed to solvents and their unexposed referents (carpenters) 18 years after the
      baseline assessment. The pattern of cognitive changes in the two groups was
      compared, with the same 10 neuropsychological tests from the test battery for
      investigating functional disorders (TUFF) that were used at baseline. The study
      included 41 floor layers and 40 carpenters. A medical examination focused on
      health at the present and during the past 18 years. An extensive exposure
      assessment made in the initial study included questionnaires, interviews, and
      measurements. Additional exposure during the follow up period was minor, as
      explored in interviews at follow up. RESULTS: The entire group of floor layers
      did not deteriorate significantly more over time than did the carpenters.
      However, among the oldest subjects (>60 years), only floor layers showed decline
      in visual memory. Moreover, the most highly exposed floor layers deteriorated
      significantly more than their referents in visual memory and perceptual speed,
      and they tended to display larger decrements in motor speed. Significant dose
      effect relations were found; higher cumulative exposure was associated with
      decrements in visual episodic memory, perceptual speed and attention, and
      visuospatial skill. CONCLUSIONS: The hypothesis that floor layers would
      deteriorate more in cognitive performance than their unexposed referents over a
      period of 18 years was partly supported by the results of this study. The results
      are consistent with the view that the negative effects of exposure to solvents
      may interact with the normal aging process, primarily at heavy exposure.

PMID- 11836471
TI  - Methodological problems in a case-referent study based on a register of
      occupational asthma.

PMID- 11836472
TI  - Nasal, eye, and skin irritation in dockyard painters.

PMID- 11836473
TI  - Response to a case of occupational asthma due to the enzymes phytase and beta
      glucanase.

PMID- 11836475
TI  - Causes and management of stress at work.

PMID- 11836476
TI  - Phototropin blue light receptors and light-induced movement responses in plants.
AB  - Two blue light receptors in Arabidopsis, termed phot1 and phot2, which contain
      flavin chromophores and have intrinsic protein kinase activity, participate in
      several physiological processes. Lin looks at the genetic evidence regarding how
      these photoreceptors mediate blue light-induced phototropism, chloroplast
      relocalization, and opening of the stomatal aperture.

PMID- 11836477
TI  - G alpha COOH-terminal minigene vectors dissect heterotrimeric G protein
      signaling.
AB  - The COOH-termini of heterotrimeric guanine nucleotide-binding protein (G protein)
      alpha subunits (Galpha) are critical for both binding to their cognate G protein
      coupled receptors (GPCRs) and determining specificity. Additionally, synthetic
      peptides corresponding to the COOH-terminus can serve as competitive inhibitors
      of receptor-G protein interactions, presumably by blocking the site on the GPCR
      that normally binds the G protein. To selectively antagonize G protein signal
      transduction events, we have generated minigene vectors that encode 14 unique
      COOH-terminal sequence for the 16 Galpha subunits. Minigene vectors expressing
      Galpha COOH-terminal peptides, or the control minigene vector, which expresses
      the inhibitory Galpha subunit (G(i)) peptide in random order, can be
      systematically introduced into cells by transfection and used to determine which
      G protein underlies a given GPCR-mediated response. Because Galpha COOH-terminal
      minigene vectors selectively block signal transduction through a given G protein,
      they are a powerful tool for dissecting out which G protein mediates a given
      biochemical or physiological function. This also provides a novel strategy for
      exploring the coupling mechanisms of receptors that interact with multiple G
      proteins, as well as for teasing out the downstream responses mediated by a
      specific G protein.

PMID- 11836484
TI  - Intramyocardial analysis of regional systolic and diastolic function in ischemic
      heart disease with Doppler tissue imaging: role of the different myocardial
      layers.
AB  - BACKGROUND: Preliminary experimental data have shown a nonuniform distribution of
      myocardial velocities (MVs) across the myocardial wall in normal conditions.
      However, after ischemic damage to the myocardium, a different pattern of
      reduction in the myocardial layers has been reported. The aim of this study is to
      analyze the spatial distribution of MVs and the resultant myocardial velocity
      gradients (MVGs) during the systolic and diastolic time periods. Doppler tissue
      imaging (DTI) in color M-mode was used to evaluate 3 different myocardial layers
      (endocardium, mesocardium, and epicardium) and their changes as a result of
      ischemia. METHODS: Thirty-two consecutive patients were studied with DTI color M
      mode: 18 patients with a history of previous or ongoing myocardial infarction and
      14 healthy subjects. Postprocessing of images was accomplished with proprietary
      software. MV and MVG values of all layers along both systolic and diastolic time
      were calculated. For temporal analysis, systole was subdivided in 3 equal
      periods. Early- and late-diastolic times were also identified. RESULTS: In
      ischemic patients, the mean MV and maximum MV throughout systole decreased
      significantly in the endocardium and mesocardium, whereas only slightly in the
      epicardium. The mean MVG was less in ischemic patients (0.66 +/- 0.11 vs 0.23 +/-
      0.15, P <.03). Temporal analysis showed a decrease in the maximal MV and MVG in
      all layers over the 3 systolic periods. This decrease was the more consistent in
      mesocardium. In diastole, there was a decrease in maximal MV in all layers, being
      more pronounced in endocardium and mesocardium. Diastolic mean MVG was shown to
      be different between control and ischemic groups (-0.2 +/- 0.05 vs -0.10 +/-
      0.04, P <.06). A significant decrease of the maximal MV in endocardium and
      mesocardium was reported in the temporal analysis during early diastole. No
      change was reported in the epicardium. The MVG value also showed a significant
      decrease (-2.69 +/- 0.29 vs -1.59 +/- 0.89, P <.02). In ischemic patients in late
      diastole, the maximum MV was increased in all layers of the myocardium, and this
      increase was observed mainly in the endocardium. An increase in the MVG (-0.78 +/
      0.18 vs -1.47 +/- 0.85, P = NS) was also reported during late diastole.
      CONCLUSION: There is a nonuniform distribution of velocities in the different
      myocardial layers under normal conditions. This distribution of velocities
      undergoes a significant change in patients with ischemic myocardial damage.
      Intramyocardial wall motion analysis could have clinical applications in both the
      early detection of ischemia and myocardial viability.

PMID- 11836485
TI  - Echo doppler assessment of left ventricular function in rats with hypertensive
      hypertrophy.
AB  - OBJECTIVE: This study attempted to establish echocardiographic measurements of
      left ventricular (LV) mass and LV systolic and diastolic function, particularly
      in rats with hypertensive heart. METHODS: M-mode LV echograms and Doppler mitral
      flow were obtained in Dahl salt-sensitive rats placed on 0.3% or 8% sodium
      chloride diet. Echo Doppler measurements were compared with catheterization and
      pathologic measurements in 54 rats for LV mass and in 45 rats for LV systolic and
      diastolic function. RESULTS: Echocardiographic measurement of LV mass correlated
      well with pathologic measurement (r = 0.94, P <.01, n = 54, SEE = 0.08 mg),
      independent of LV size, aging, and therapeutic intervention. Endocardial
      fractional shortening (FS) correlated with LV peak + dP/dt (r = 0.56, n = 45, P
      <.01), and the correlation was improved to r = 0.71 if 11 rats with marked LV
      hypertrophy were excluded. Midwall FS correlated well with LV peak + dP/dt (r =
      0.72, n = 45, P <.01) even if rats with extremely thickened ventricular wall were
      included. If midwall FS was lower than 14%, LV systolic dysfunction was very
      likely (sensitivity 67%, specificity 91%). Association of mitral E/A ratio of 2.0
      or greater with deceleration time of shorter than 35 ms was an accurate indicator
      of elevated LV end-diastolic pressure (sensitivity 82%, specificity 86%) and
      increased lung weight because of congestive heart failure (sensitivity 89%,
      specificity 96%) in rats with hypertension. CONCLUSION: LV mass, LV systolic
      function, and LV end-diastolic pressure were assessable with echo Doppler in rats
      with hypertensive heart.

PMID- 11836486
TI  - Objective assessment of left ventricular wall motion from contrast-enhanced power
      modulation images.
AB  - There is no method to objectively evaluate left ventricular (LV) function from
      contrast-enhanced images. We tested the feasibility of evaluating regional LV
      function by using power modulation imaging. In protocol 1, 9 anesthetized closed
      chest pigs were studied. Images were obtained during contrast infusion at
      baseline, during LAD occlusion and reperfusion. In protocol 2, images were
      obtained in 20 patients (14 wall-motion abnormalities; 6 controls) during
      contrast enhancement. Off-line, frame-by-frame, semiautomated endocardial border
      detection was followed by color encoding of endocardial motion, followed by
      segmentation and calculation of regional fractional area changes. In all animals,
      coronary occlusions resulted in hypokinesis and decreased fractional area changes
      in LAD-related segments only, which were reversed during reperfusion. In
      patients, wall-motion analysis was in agreement with an expert reader of dynamic
      images in 92.5% segments, with interobserver variability of 12.5%. Color encoding
      of endocardial motion from contrast-enhanced power modulation images allows
      accurate quantitative assessment of regional LV function.

PMID- 11836487
TI  - Three-dimensional echocardiographic measurement of left ventricular wall
      thickness: In vitro and in vivo validation.
AB  - INTRODUCTION: Three-dimensional (3D) echocardiography has been shown to
      accurately measure left ventricular (LV) volume and mass. This study evaluated
      the accuracy of 3D echocardiography and the CenterSurface method for measuring LV
      wall thickness in vitro and in vivo. METHOD: Three-dimensional echocardiography
      scans, obtained from 7 LV phantoms and subjects having healthy (n = 5) or
      diseased (n = 8) hearts, were digitized. Endocardial and epicardial borders were
      outlined and used in 3D LV reconstruction. In vitro wall thickness was compared
      with true micrometer measurements. Three-dimensional in vivo wall thickness was
      compared with 2-dimensional (2D) thickness measured by the centerline method.
      RESULTS: The in vitro 3D echocardiography measurements agreed closely with true
      wall thickness (P <.0001), as did in vivo measurements (P <.0001). CONCLUSION:
      Three-dimensional echocardiography reconstruction has previously been shown to
      provide accurate representation of LV shape in addition to volume and mass. This
      study demonstrates that the CenterSurface method provides accurate quantification
      of wall thickness.

PMID- 11836489
TI  - Comparison of left atrial dimensions by transesophageal and transthoracic
      echocardiography.
AB  - Left atrial (LA) size, as determined by transthoracic echocardiography (TTE),
      predicts the risk of atrial fibrillation and stroke and the success of
      cardioversion. Transesophageal echocardiography (TEE) is increasingly used in
      these clinical situations. However, unlike TTE, measurement of LA size by TEE has
      not been standardized. To validate TEE measurement, we determined LA dimensions
      in 4 standard views by TTE at the same time in 121 patients undergoing TEE. The
      mid-esophageal basal short-axis view at the level of the aortic valve (TEE 30-60)
      was the only view in which complete visualization of a LA axis of measurement
      could be obtained with an acceptably high yield (97.2%). The measurement from
      this view provided a value that had the highest correlation between TTE and TEE
      (r = 0.758, P <.0001, 95% confidence interval 0.68-0.86; bias 0.37 +/- 1 cm).
      Overall, TEE underestimated the LA dimension by 9% compared with TTE. These
      results suggest that the short-axis view at the level of the aortic valve is the
      preferred site for measuring the LA dimension by TEE.

PMID- 11836488
TI  - Right ventricular dP/dt/P(max), not dP/dt(max), noninvasively derived from
      tricuspid regurgitation velocity is a useful index of right ventricular
      contractility.
AB  - BACKGROUND: Although right ventricular (RV) contractility is important in
      determining functional capacity, few quantification methods are clinically
      available. RV dP/dt(max) can be assessed by Doppler echocardiography by using
      tricuspid regurgitation (TR) but is not routinely used because of its dependency
      on a Doppler incident angle and preload. Doppler-derived dP/dt/P(max) is
      relatively insensitive to preload and theoretically independent of the incident
      angle. We investigated the clinical feasibility of this index as an RV
      contractility index. METHODS: We computed RV dP/dt(max) and dP/dt/P(max) from the
      TR-derived RV pressure in 68 patients with dominant RV failure (13 in New York
      Heart Association [NYHA] class I, 33 in class II, 17 in class III, and 5 in class
      IV). Peak oxygen consumption (peak VO(2)) was measured in 20 patients during a
      maximal bicycle ergometer test. RESULTS: dP/dt(max) did not significantly
      correlate with NYHA class. In contrast, dP/dt/P(max) decreased monotonically with
      the functional class (r = -0.49, P <.0001), and correlated with peak VO(2) (r =
      0.66, P <.002). CONCLUSION: TR-derived dP/dt/P(max), not dP/dt(max), is a
      clinically useful index of RV contractility, allowing researchers to account for
      the functional capacity.

PMID- 11836490
TI  - Catheter-based interventions guided solely by a new phased-array intracardiac
      imaging catheter: in vivo experimental studies.
AB  - BACKGROUND: Intracardiac echocardiography (ICE) has had useful but limited use
      during interventional procedures because of technologic limitations. We used a
      novel phased-array ICE device (AcuNav) with 2-dimensional sector imaging and full
      Doppler capability to see whether it could guide cardiac interventions without
      fluoroscopy. METHODS: Twelve dogs were studied, and we performed atrial
      septostomy, tricuspid, and pulmonary valve disruption using only ICE.
      Preinterventional and postinterventional anatomic and hemodynamic data were
      noted. RESULTS: All attempts were successful in the placement of the ICE catheter
      (100%). We attempted septostomy on 11 dogs and were successful 8 times (73%).
      Tricuspid valve disruption and balloon dilatation were performed successfully on
      5 dogs (100%). We attempted pulmonary valve disruption on 4 dogs and could always
      correctly place the guidewire (100%). We performed pulmonary valve balloon
      dilatation on one dog (25%). A comprehensive echocardiographic examination was
      always possible. CONCLUSION: This new ICE device can guide interventions without
      fluoroscopy. However, further studies are needed to evaluate whether it can
      replace fluoroscopy.

PMID- 11836491
TI  - Maternal psychological impact of fetal echocardiography.
AB  - The maternal psychological impact of fetal echocardiography may be deleterious in
      the face of newly diagnosed congenital heart disease. This questionnaire-based
      study prospectively examined the psychological impact of both normal and abnormal
      fetal echocardiography. Normal fetal echocardiography decreased maternal anxiety,
      increased happiness, and increased the closeness women felt toward their unborn
      children. In contrast, when fetal echocardiography detected congenital heart
      disease, maternal anxiety typically increased, and mothers commonly felt less
      happy about being pregnant. However, among women who had recently delivered
      infants with congenital heart disease, those who had had fetal echocardiography
      during the pregnancy felt less responsible for their infants' defects and tended
      to have improved their relationships with the infants' fathers after the prenatal
      diagnosis of congenital heart disease. Further study of the psychological and
      medical impact of fetal echocardiography will be necessary to define and optimize
      the clinical value of this powerful diagnostic tool.

PMID- 11836492
TI  - Recommendations for quantification of Doppler echocardiography: a report from the
      Doppler Quantification Task Force of the Nomenclature and Standards Committee of
      the American Society of Echocardiography.

PMID- 11836493
TI  - Embolization of a huge tricuspid valve bacterial vegetation.
AB  - A case of a woman who had tricuspid valve bacterial endocarditis is presented.
      Her course was complicated by persistent disseminated intravascular coagulation
      and acute renal failure, followed by pulmonary embolization of the vegetation.
      Transthoracic echocardiography showed almost complete obstruction of the right
      pulmonary artery. The case demonstrates the impressive size to which right-sided
      infective vegetations can progress and the relative paucity of symptoms and
      hemodynamic derangements with which they may be associated, even in the context
      of potentially life-threatening complications.

PMID- 11836494
TI  - Giant aneurysm of the membranous ventricular septum extending outside the heart:
      diagnosis by transthoracic color flow Doppler echocardiography.
AB  - Aneurysm of the membranous ventricular septum (AMS) is a congenital cardiac
      anomaly often associated with ventricular septal defect. This aneurysm usually
      pouches into the right side of the heart and remains intracardiac. An AMS that
      extends outside of the heart is rare. We report an unusual case of a giant
      extracardiac AMS diagnosed by transthoracic color flow Doppler echocardiography.

PMID- 11836495
TI  - Value of transesophageal echocardiography in the diagnosis of compressive,
      atypically located pericardial cysts.
AB  - Pericardial cysts are not common and rarely cause symptoms. We report 2 cases of
      atypically located pericardial cysts with hemodynamic compromise because of the
      direct compression of the pulmonary veins and the right pulmonary artery. In the
      first case, transesophageal echocardiography (TEE) disclosed a round cystic mass
      compressing the posterior wall of the right pulmonary artery, with blood flow
      reduction in the right lung. Because of the symptoms, the pericardial cyst was
      drained and the patient had an uneventful 1-year follow-up. In the second case, a
      large cystic mass compressing the left atrium and the pulmonary vein outflow was
      clearly shown by TEE in a patient with severe respiratory distress, cyanosis, and
      low blood pressure. A left ventricular thoracotomy was performed with the
      drainage of 500 mL serous fluid from the cyst.

PMID- 11836496
TI  - Correlation between quantitative left atrial spontaneous echocardiographic
      contrast and intact fibrinogen levels in mitral stenosis.

PMID- 11836498
TI  - Hermansky-Pudlak syndrome is caused by mutations in HPS4, the human homolog of
      the mouse light-ear gene.
AB  - Hermansky-Pudlak syndrome (HPS) is a disorder of organelle biogenesis in which
      oculocutaneous albinism, bleeding and pulmonary fibrosis result from defects of
      melanosomes, platelet dense granules and lysosomes. HPS is common in Puerto Rico,
      where it is caused by mutations in the genes HPS1 and, less often, HPS3 (ref. 8).
      In contrast, only half of non-Puerto Rican individuals with HPS have mutations in
      HPS1 (ref. 9), and very few in HPS3 (ref. 10). In the mouse, more than 15 loci
      manifest mutant phenotypes similar to human HPS, including pale ear (ep), the
      mouse homolog of HPS1 (refs 13,14). Mouse ep has a phenotype identical to another
      mutant, light ear (le), which suggests that the human homolog of le is a possible
      human HPS locus. We have identified and found mutations of the human le homolog,
      HPS4, in a number of non-Puerto Rican individuals with HPS, establishing HPS4 as
      an important HPS locus in humans. In addition to their identical phenotypes, le
      and ep mutant mice have identical abnormalities of melanosomes, and in
      transfected melanoma cells the HPS4 and HPS1 proteins partially co-localize in
      vesicles of the cell body. In addition, the HPS1 protein is absent in tissues of
      le mutant mice. These results suggest that the HPS4 and HPS1 proteins may
      function in the same pathway of organelle biogenesis.

PMID- 11836499
TI  - BRCA1 regulates the G2/M checkpoint by activating Chk1 kinase upon DNA damage.
AB  - The breast cancer tumor-suppressor gene, BRCA1, encodes a protein with a BRCT
      domain-a motif that is found in many proteins that are implicated in DNA damage
      response and in genome stability. Phosphorylation of BRCA1 by the DNA damage
      response proteins ATM, ATR and hCds1/Chk2 changes in response to DNA damage and
      at replication-block checkpoints. Although cells that lack BRCA1 have an abnormal
      response to DNA damage, the exact role of BRCA1 in this process has remained
      unclear. Here we show that BRCA1 is essential for activating the Chk1 kinase that
      regulates DNA damage-induced G2/M arrest. Thus, BRCA1 controls the expression,
      phosphorylation and cellular localization of Cdc25C and Cdc2/cyclin B kinase
      proteins that are crucial for the G2/M transition. We show that BRCA1 regulates
      the expression of both Wee1 kinase, an inhibitor of Cdc2/cyclin B kinase, and the
      14-3-3 family of proteins that sequesters phosphorylated Cdc25C and Cdc2/cyclin B
      kinase in the cytoplasm. We conclude that BRCA1 regulates key effectors that
      control the G2/M checkpoint and is therefore involved in regulating the onset of
      mitosis.

PMID- 11836500
TI  - A bisexually reproducing all-triploid vertebrate.
AB  - Green toads are common in the Palaearctic region, where they have differentiated
      into several taxa. The toads exist with variable amounts of ploidy, similar to
      other anuran species or reptiles. In vertebrate biology, the very rare occurrence
      of triploidy is coupled with infertility or unisexuality, or requires the
      coexistence of individuals of different ploidy in a reproductive community. The
      reproduction of naturally occurring triploids has been reported to occur only
      through parthenogenesis, gynogenesis or hybridogenesis. The bisexual reproduction
      of pure triploids has been considered to be impossible because of the problem of
      equally distributing three chromosome sets in meiosis. Here we report
      geographically isolated populations of green toads (Bufo viridis complex) that
      are all-triploid and reproduce bisexually.

PMID- 11836501
TI  - Early death of mice cloned from somatic cells.
AB  - Here we report that the lifespan of mice cloned from somatic cells is
      significantly shorter than that of genotype- and sex-matched controls, most
      likely due to severe pneumonia and hepatic failure. This finding demonstrates the
      possibility of long-term deleterious effects of somatic-cell cloning, even after
      normal birth.

PMID- 11836502
TI  - Pathogen stress increases somatic recombination frequency in Arabidopsis.
AB  - Evolution is based on genetic variability and subsequent phenotypic selection.
      Mechanisms that modulate the rate of mutation according to environmental cues,
      and thus control the balance between genetic stability and flexibility, might
      provide a distinct evolutionary advantage. Stress-induced mutations stimulated by
      unfavorable environments, and possible mechanisms for their induction, have been
      described for several organisms, but research in this area has mainly focused on
      microorganisms. We have analyzed the influence of adverse environmental
      conditions on the genetic stability of the higher plant Arabidopsis thaliana.
      Here we show that a biotic stress factor-attack by the oomycete pathogen
      Peronospora parasitica-can stimulate somatic recombination in Arabidopsis. The
      same effect was observed when plant pathogen-defense mechanisms were activated by
      the chemicals 2,6-dichloroisonicotinic acid (INA) or benzothiadiazole (BTH), or
      by a mutation (cim3). Together with previous studies of recombination induced by
      abiotic factors, these findings suggest that increased somatic recombination is a
      general stress response in plants. The increased genetic flexibility might
      facilitate evolutionary adaptation of plant populations to stressful
      environments.

PMID- 11836503
TI  - The complex structure and dynamic evolution of human subtelomeres.
AB  - Subtelomeres are extraordinarily dynamic and variable regions near the ends of
      chromosomes. They are defined by their unusual structure: patchworks of blocks
      that are duplicated near the ends of multiple chromosomes. Duplications among
      subtelomeres have spawned small gene families, making inter-individual variation
      in subtelomeres a potential source of phenotypic diversity. The ectopic
      recombination that occurs between subtelomeres might also have a role in
      reconstituting telomeres in the absence of telomerase. However, the propensity
      for subtelomeres to interchange is a double-edged sword, as extensive
      subtelomeric homology can mediate deleterious rearrangements of the ends of
      chromosomes to cause human disease.

PMID- 11836504
TI  - Establishment of vertebrate left-right asymmetry.
AB  - The generation of morphological, such as left-right, asymmetry during development
      is an integral part of the establishment of a body plan. Until recently, the
      molecular basis of left-right asymmetry was a mystery, but studies indicate that
      Nodal and the Lefty proteins, transforming growth factor-beta-related molecules,
      have a central role in generating asymmetric signals. Although the initial
      mechanism of symmetry breaking remains unknown, developmental biologists are
      beginning to analyse the pathway that leads to left-right asymmetry establishment
      and maintenance.

PMID- 11836505
TI  - The mouse: genetics meets behaviour.
AB  - Genetic studies in the mouse are important in the elucidation of molecular
      pathways that underlie behaviour. The advantages of the mouse for behavioural
      studies include an extensive array of genetic technologies and an elaborate
      behavioural repertoire that can be used to create models of human disease. This
      review discusses the relative advantages of forward and reverse genetic
      approaches to studying the genetic basis of behaviour in the mouse, and the
      complexities that behavioural studies need to address, such as phenotypic
      variability, genetic background effects and pleiotropy.

PMID- 11836506
TI  - The art and design of genetic screens: Arabidopsis thaliana.
AB  - Molecular genetic studies rely on well-characterized organisms that can be easily
      manipulated. Arabidopsis thaliana--the model system of choice for plant
      biologists--allows efficient analysis of plant function, combining classical
      genetics with molecular biology. Although the complete sequence of the
      Arabidopsis genome allows the rapid discovery of the molecular basis of a
      characterized mutant, functional characterization of the Arabidopsis genome
      depends on well-designed forward genetic screens, which remain a powerful
      strategy to identify genes that are involved in many aspects of the plant life
      cycle.

PMID- 11836507
TI  - The rapid evolution of reproductive proteins.
AB  - Many genes that mediate sexual reproduction, such as those involved in gamete
      recognition, diverge rapidly, often as a result of adaptive evolution. This
      widespread phenomenon might have important consequences, such as the
      establishment of barriers to fertilization that might lead to speciation.
      Sequence comparisons and functional studies are beginning to show the extent to
      which the rapid divergence of reproductive proteins is involved in the speciation
      process.

PMID- 11836508
TI  - Ownership of human tissue and the law.
AB  - Genetic researchers and medical practitioners often need to obtain access to
      stored human tissue without consent from the people concerned. But the laws that
      relate to the ownership of, and control over, stored human tissue are at present
      unclear, especially in the light of recent cases and inquiries. Here, I discuss
      how the law might be clarified, and argue that the law should allow stored human
      tissue to be used without consent, providing that this occurs with ethical
      approval and that the confidentiality of the donor is protected.

PMID- 11836509
TI  - Rejuvenating views of the ageing process.
AB  - Commonly held assumptions about the ageing process have guided and directed
      research in this important area over many years. Recent evidence, however, from
      disciplines as diverse as molecular genetics, clinical epidemiology and
      demography, provide a direct challenge to the validity of many of these
      assumptions. So, the time is ripe to re-examine these assumptions about the
      ageing process and to rethink the scientific foundations of the field.

PMID- 11836510
TI  - Phytochrome photosensory signalling networks.
AB  - Light is life for plants. To continuously assess and adapt to fluctuations in the
      quality and quantity of this essential commodity, plants deploy sensory
      photoreceptors, including the phytochromes. Having captured an incoming photon,
      the activated phytochrome molecule must relay this information to nuclear genes
      that are poised to respond by directing appropriate adjustments in growth and
      development. Defining the intricate intracellular signalling networks through
      which this sensory information is transduced is an area of intense research
      activity.

PMID- 11836511
TI  - The vacuolar (H+)-ATPases--nature's most versatile proton pumps.
AB  - The pH of intracellular compartments in eukaryotic cells is a carefully
      controlled parameter that affects many cellular processes, including
      intracellular membrane transport, prohormone processing and transport of
      neurotransmitters, as well as the entry of many viruses into cells. The
      transporters responsible for controlling this crucial parameter in many
      intracellular compartments are the vacuolar (H+)-ATPases (V-ATPases). Recent
      advances in our understanding of the structure and regulation of the V-ATPases,
      together with the mapping of human genetic defects to genes that encode V-ATPase
      subunits, have led to tremendous excitement in this field.

PMID- 11836512
TI  - Prestin, a new type of motor protein.
AB  - Prestin, a transmembrane protein found in the outer hair cells of the cochlea,
      represents a new type of molecular motor, which is likely to be of great interest
      to molecular cell biologists. In contrast to enzymatic-activity-based motors,
      prestin is a direct voltage-to-force converter, which uses cytoplasmic anions as
      extrinsic voltage sensors and can operate at microsecond rates. As prestin
      mediates changes in outer hair cell length in response to membrane potential
      variations, it might be responsible for sound amplification in the mammalian
      hearing organ.

PMID- 11836513
TI  - Deadly encounter: ubiquitin meets apoptosis.
AB  - The ubiquitin/proteasome pathway is the main non-lysosomal route for
      intracellular protein degradation in eukaryotes. It is instrumental to various
      cellular processes, such as cell-cycle progression, transcription and antigen
      processing. Recent findings also substantiate a pivotal role of the
      ubiquitin/proteasome pathway in the regulation of apoptosis. Regulatory molecules
      that are involved in programmed cell death have been identified as substrates of
      the proteasome. Moreover, key regulators of apoptosis themselves seem to have an
      active part in the proteolytic inactivation of death executors.

PMID- 11836514
TI  - Secretory lysosomes.
AB  - Regulated secretion of stored secretory products is important in many cell types.
      In contrast to professional secretory cells, which store their secretory products
      in specialized secretory granules, some secretory cells store their secretory
      proteins in a dual-function organelle, called a secretory lysosome. Functionally,
      secretory lysosomes are unusual in that they serve both as a degradative and as a
      secretory compartment. Recent work shows that cells with secretory lysosomes use
      new sorting and secretory pathways. The importance of these organelles is
      highlighted by several genetic diseases, in which immune function and
      pigmentation--two processes that normally involve secretory lysosomes--are
      impaired.

PMID- 11836515
TI  - Microscopy: an art?
AB  - There can be no doubt that the finest creator of beauty is Mother Nature. And in
      many ways, science is the exploration of this beauty and of the mechanisms that
      have created it. Microscopy, as a technique in scientific investigation, has had
      a key role in uncovering nature's beauty, which has led some to propose that
      microscopy could be described as an art or even an art form. But is this claim
      justified?

PMID- 11836516
TI  - Studying actin-dependent processes in tissue culture.
AB  - The cytoskeletal organization of cells that are grown in tissue culture is often
      very different from that of cells in living organisms. This casts some doubt as
      to whether information that comes from studying actin-dependent cellular
      processes--such as cell motility or differentiation--in cells that are cultured
      under these conditions is physiologically relevant. Studies on cells grown in
      improved two-dimensional- and three-dimensional-culture systems that closely
      mimic the in vivo extracellular-matrix environment should provide a more accurate
      picture of actin-cytoskeletal function in the living organism.

PMID- 11836517
TI  - The structure and function of glutamate receptor ion channels.
AB  - As in the case of many ligand-gated ion channels, the biochemical and
      electrophysiological properties of the ionotropic glutamate receptors have been
      studied extensively. Nevertheless, we still do not understand the molecular
      mechanisms that harness the free energy of agonist binding, first to drive
      channel opening, and then to allow the channel to close (desensitize) even though
      agonist remains bound. Recent crystallographic analyses of the ligand-binding
      domains of these receptors have identified conformational changes associated with
      agonist binding, yielding a working hypothesis of channel function. This opens
      the way to determining how the domains and subunits are assembled into an
      oligomeric channel, how the domains are connected, how the channel is formed, and
      where it is located relative to the ligand-binding domains, all of which govern
      the processes of channel activation and desensitization.

PMID- 11836518
TI  - Emerging structure of the nicotinic acetylcholine receptors.
AB  - The conversion of acetylcholine binding into ion conduction across the membrane
      is becoming more clearly understood in terms of the structure of the receptor and
      its transitions. A high-resolution structure of a protein that is homologous to
      the extracellular domain of the receptor has revealed the binding sites and
      subunit interfaces in great detail. Although the structures of the membrane and
      cytoplasmic domains are less well determined, the channel lining and the
      determinants of selectivity have been mapped. The location and structure of the
      gates, and the coupling between binding sites and gates, remain to be
      established.

PMID- 11836519
TI  - Potassium channel structures.
AB  - The molecular basis of K+ channel function is universally conserved. K+ channels
      allow K+ flux and are essential for the generation of electric current across
      excitable membranes. K+ channels are also the targets of various intracellular
      control mechanisms, such that the suboptimal regulation of channel function might
      be related to pathological conditions. Because of the fundamental role of K+
      channels in controlling membrane excitability, a structural understanding of
      their function and regulation will provide a useful framework for understanding
      neuronal physiology. Many recent physiological and crystallographic studies have
      led to new insights into the workings of K+ channels.

PMID- 11836520
TI  - Parallels between cerebellum- and amygdala-dependent conditioning.
AB  - Recent evidence from cerebellum-dependent motor learning and amygdala-dependent
      fear conditioning indicates that, despite being mediated by different brain
      systems, these forms of learning might use a similar sequence of events to form
      new memories. In each case, learning seems to induce changes in two different
      groups of neurons. Changes in the first class of cells are induced very rapidly
      during the initial stages of learning, whereas changes in the second class of
      cells develop more slowly and are resistant to extinction. So, anatomically
      distinct cell populations might contribute differentially to the initial encoding
      and the long-term storage of memory in these two systems.

PMID- 11836521
TI  - Evolutionary autonomous agents: a neuroscience perspective.
AB  - In this article, I discuss the use of neurally driven evolutionary autonomous
      agents (EAAs) in neuroscientific investigations. Two fundamental questions are
      addressed. Can EAA studies shed new light on the structure and function of
      biological nervous systems? And can these studies lead to the development of new
      tools for neuroscientific analysis? The value and significant potential of EAA
      modelling in both respects is demonstrated and discussed. Although the study of
      EAAs for neuroscience research still faces difficult conceptual and technical
      challenges, it is a promising and timely endeavour.

PMID- 11836522
TI  - What does fMRI tell us about neuronal activity?
AB  - In recent years, cognitive neuroscientists have taken great advantage of
      functional magnetic resonance imaging (fMRI) as a non-invasive method of
      measuring neuronal activity in the human brain. But what exactly does fMRI tell
      us? We know that its signals arise from changes in local haemodynamics that, in
      turn, result from alterations in neuronal activity, but exactly how neuronal
      activity, haemodynamics and fMRI signals are related is unclear. It has been
      assumed that the fMRI signal is proportional to the local average neuronal
      activity, but many factors can influence the relationship between the two. A
      clearer understanding of how neuronal activity influences the fMRI signal is
      needed if we are correctly to interpret functional imaging data.

PMID- 11836523
TI  - What's new with the amnesic patient H.M.?
AB  - H.M. became amnesic in 1953. Since that time, nearly 100 investigators, first at
      the Montreal Neurological Institute and since 1966 at the Massachusetts Institute
      of Technology, have participated in studying him. We all understand the rare
      opportunity we have had to work with him, and we are grateful for his dedication
      to research. He has taught us a great deal about the cognitive and neural
      organization of memory. We are in his debt.

PMID- 11836524
TI  - SMIF, a Smad4-interacting protein that functions as a co-activator in TGFbeta
      signalling.
AB  - Proteins of the transforming growth factor beta(TGFbeta) superfamily regulate
      diverse cellular responses, including cell growth and differentiation. After
      TGFbeta stimulation, receptor-associated Smads are phosphorylated and form a
      complex with the common mediator Smad4. Here, we report the cloning of SMIF, a
      ubiquitously expressed, Smad4-interacting transcriptional co-activator. SMIF
      forms a TGFbeta/bone morphogenetic protein 4 (BMP4)-inducible complex with Smad4,
      but not with others Smads, and translocates to the nucleus in a TGFbeta/BMP4
      inducible and Smad4-dependent manner. SMIF possesses strong intrinsic TGFbeta
      inducible transcriptional activity, which is dependent on Smad4 in mammalian
      cells and requires p300/CBP. A point mutation in Smad4 abolished binding to SMIF
      and impaired its activity in transcriptional assays. Overexpression of wild-type
      SMIF enhanced expression of TGFbeta/BMP regulated genes, whereas a dominant
      negative SMIF mutant suppressed expression. Furthermore, dominant-negative SMIF
      is able to block TGFbeta-induced growth inhibition. In a knockdown approach with
      morpholino-antisense oligonucleotides targeting zebrafish SMIF, severe but
      distinct phenotypic defects were observed in zebrafish embryos. Thus, we propose
      that SMIF is a crucial activator of TGFbeta signalling.

PMID- 11836525
TI  - Interdependent nuclear accumulation of budding yeast Cdt1 and Mcm2-7 during G1
      phase.
AB  - Cdt1 is essential for loading Mcm2-7 proteins into prereplicative complexes (pre
      RCs) during replication licensing and has been found in organisms as diverse as
      fission yeast and humans. We have identified a homologue of Cdt1 in Saccharomyces
      cerevisiae, which is required for pre-RC assembly. We show that, like Mcm2-7p,
      Cdt1p accumulates in the nucleus during G1 phase and is excluded from the nucleus
      later in the cell cycle by cyclin dependent kinases (cdks). Cdt1p interacts with
      the Mcm2--7p complex, and the nuclear accumulation of these proteins during G1 is
      interdependent. This coregulation of Cdt1p and Mcm2-7p represents a novel level
      of pre-RC control.

PMID- 11836526
TI  - Hakai, a c-Cbl-like protein, ubiquitinates and induces endocytosis of the E
      cadherin complex.
AB  - In epithelial cells, tyrosine kinases induce the tyrosine phosphorylation and
      ubiquitination of the E-cadherin complex, which induces endocytosis of E
      cadherin. With a modified yeast 2-hybrid system, we isolated Hakai, an E-cadherin
      binding protein, which we have identified as an E3 ubiquitin-ligase. Hakai
      contains SH2, RING, zinc-finger and proline-rich domains, and interacts with E
      cadherin in a tyrosine phosphorylation-dependent manner, inducing ubiquitination
      of the E-cadherin complex. Expression of Hakai in epithelial cells disrupts cell-
      cell contacts and enhances endocytosis of E-cadherin and cell motility. Through
      dynamic recycling of E-cadherin, Hakai can thus modulate cell adhesion, and could
      participate in the regulation of epithelial--mesenchymal transitions in
      development or metastasis.

PMID- 11836527
TI  - Natural cytotoxicity uncoupled from the Syk and ZAP-70 intracellular kinases.
AB  - The intracellular signals that trigger natural cytotoxicity have not been clearly
      determined. The Syk and ZAP-70 tyrosine kinases are essential for cellular
      activation initiated by B and T cell antigen receptors and may drive natural
      killer (NK) cell cytotoxicity via receptors bearing immunoreceptor tyrosine-based
      activation motifs (ITAMs). However, we found that, unlike B and T cells, NK cells
      developed in Syk-/-ZAP-70-/- mice and, despite their nonfunctional ITAMs, lysed
      various tumor targets in vitro and eliminated tumor cells in vivo, including
      those without NKG2D ligands. The simultaneous inhibition of phosphatidyl inositol
      3 kinase and Src kinases abrogated the cytolytic activity of Syk-/-ZAP-70-/- NK
      cells and strongly reduced that of wild-type NK cells. This suggests that
      distinct and redundant signaling pathways act synergistically to trigger natural
      cytotoxicity.

PMID- 11836528
TI  - Rap1A positively regulates T cells via integrin activation rather than inhibiting
      lymphocyte signaling.
AB  - T cell receptor (TCR) stimulation activates the small GTPase Rap1A, which is
      reported to antagonize Ras signaling and induces T cell anergy. To address its
      role in vivo, we generated transgenic mice that constitutively expressed active
      Rap1A within the T cell lineage. We found that active Rap1A did not interfere
      with the Ras signaling pathway or antagonize T cell activation. Instead of
      anergy, the T lymphocytes that constitutively expressed active Rap1A showed
      enhanced TCR-mediated responses, both in thymocytes and mature T cells. In
      addition, Rap1A activation was sufficient to induce strong activation of the
      beta1 and beta2 integrins via an avidity-modulation mechanism. This shows that,
      far from playing an inhibitory role during T cell activation, Rap1A positively
      influences T cells by augmenting lymphocyte responses and directing integrin
      activation.

PMID- 11836529
TI  - Impairment of immunological memory in the absence of MHC despite survival of
      memory T cells.
AB  - The mechanisms by which immunological memory is maintained after infection or
      vaccination are still a matter of debate. Long-term survival of memory T cells
      does not require major histocompatibility complex (MHC) contact. We show here
      that compared with memory CD4+ T cells that maintain contact with MHC class II,
      memory CD4+ T cells deprived of MHC class II contact show distinct functional
      defects upon antigen re-encounter. Thus, in contrast to their survival,
      maintenance of the typical quality of memory T cells crucially depends on MHC
      derived signals.

PMID- 11836531
TI  - Boosting of neuronal firing evoked with asynchronous and synchronous inputs to
      the dendrite.
AB  - Dendritic conductances have previously been shown to boost excitatory
      postsynaptic potentials (EPSPs). To determine whether this boosting translates to
      an increase in the efficacy for evoking action potentials, we injected barrages
      of EPSPs that simulate the inputs generated by a population of presynaptic cells
      into either the dendrite or the soma of pyramidal neurons in vitro. Although the
      individual dendritic and somatic EPSPs were identical, barrages delivered to the
      dendrite generated much higher firing rates. Boosting occurred when the simulated
      cells fired asynchronously and synchronously. This Na+-mediated boosting, which
      was manifested during repetitive firing, may compensate functionally for
      electrotonic attenuation of EPSPs.

PMID- 11836530
TI  - Rhythmic gene expression in pituitary depends on heterologous sensitization by
      the neurohormone melatonin.
AB  - In mammals, many daily cycles are driven by a central circadian clock, which is
      based on the cell-autonomous rhythmic expression of clock genes. It is not clear,
      however, how peripheral cells are able to interpret the rhythmic signals
      disseminated from this central oscillator. Here we show that cycling expression
      of the clock gene Period1 in rodent pituitary cells depends on the heterologous
      sensitization of the adenosine A2b receptor, which occurs through the nocturnal
      activation of melatonin mt1 receptors. Eliminating the impact of the neurohormone
      melatonin simultaneously suppresses the expression of Period1 and evokes an
      increase in the release of pituitary prolactin. Our findings expose a mechanism
      by which two convergent signals interact within a temporal dimension to establish
      high-amplitude, precise and robust cycles of gene expression.

PMID- 11836533
TI  - Specificity of cold thermotransduction is determined by differential ionic
      channel expression.
AB  - Sensations of cold are mediated by specific thermoreceptor nerve endings excited
      by low temperature and menthol. Here we identify a population of cold-sensitive
      cultured mouse trigeminal ganglion neurons with a unique set of biophysical
      properties. Their impulse activity during cooling and menthol application was
      similar to that of cold thermoreceptor fibers in vivo. We show that cooling
      closes a background K+ channel, causing depolarization and firing that is limited
      by the slower reduction of a cationic inward current (Ih). In cold-insensitive
      neurons, firing is prevented by a slow, transient, 4-AP-sensitive K+ current
      (IKD) that acts as an excitability brake. In addition, pharmacological blockade
      of IKD induced thermosensitivity in cold-insensitive neurons, a finding that may
      explain cold allodynia in neuropathic pain. These results suggest that cold
      sensitivity is not associated to a specific transduction molecule but instead
      results from a favorable blend of ionic channels expressed in a small subset of
      sensory neurons.

PMID- 11836532
TI  - TrkB receptor signaling is required for establishment of GABAergic synapses in
      the cerebellum.
AB  - Neurotrophins are essential to the normal development and maintenance of the
      nervous system. Neurotrophin signaling is mediated by Trk family tyrosine kinases
      such as TrkA, TrkB and TrkC, as well as by the pan-neurotrophin receptor p75NTR.
      Here we have deleted the trkB gene in cerebellar precursors by Wnt1-driven Cre-
      mediated recombination to study the function of the TrkB in the cerebellum.
      Despite the absence of TrkB, the mature cerebellum of mutant mice appears similar
      to that of wild type, with all types of cell present in normal numbers and
      positions. Granule and Purkinje cell dendrites appear normal and the former have
      typical numbers of excitatory synapses. By contrast, inhibitory interneurons are
      strongly affected: although present in normal numbers, they express reduced
      amounts of GABAergic markers and develop reduced numbers of GABAergic boutons and
      synaptic specializations. Thus, TrkB is essential to the development of GABAergic
      neurons and regulates synapse formation in addition to its role in the
      development of axon terminals.

PMID- 11836534
TI  - The PWWP domain of mammalian DNA methyltransferase Dnmt3b defines a new family of
      DNA-binding folds.
AB  - The PWWP domain is a weakly conserved sequence motif found in > 60 eukaryotic
      proteins, including the mammalian DNA methyltransferases Dnmt3a and Dnmt3b. These
      proteins often contain other chromatin-association domains. A 135-residue PWWP
      domain from mouse Dnmt3b (amino acids 223--357) has been structurally
      characterized at 1.8 A resolution. The N-terminal half of this domain resembles a
      barrel-like five-stranded structure, whereas the C-terminal half contains a five
      helix bundle. The two halves are packed against each other to form a single
      structural module that exhibits a prominent positive electrostatic potential. The
      PWWP domain alone binds DNA in vitro, probably through its basic surface. We also
      show that recombinant Dnmt3b2 protein (a splice variant of Dnmt3b) and two N
      terminal deletion mutants (Delta218 and Delta369) have approximately equal methyl
      transfer activity on unmethylated and hemimethylated CpG-containing
      oligonucleotides. The Delta218 protein, which includes the PWWP domain, binds DNA
      more strongly than Delta369, which lacks the PWWP domain.

PMID- 11836535
TI  - Nanoseconds molecular dynamics simulation of primary mechanical energy transfer
      steps in F1-ATP synthase.
AB  - The mitochondrial membrane protein FoF1-ATP synthase synthesizes adenosine
      triphosphate (ATP), the universal currency of energy in the cell. This process
      involves mechanochemical energy transfer from a rotating asymmetric gamma-'stalk'
      to the three active sites of the F1 unit, which drives the bound ATP out of the
      binding pocket. Here, the primary structural changes associated with this energy
      transfer in F1-ATP synthase were studied with multi-nanosecond molecular dynamics
      simulations. By forced rotation of the gamma-stalk that mimics the effect of
      proton motive Fo-rotation during ATP synthesis, a time-resolved atomic model for
      the structural changes in the F1 part in terms of propagating conformational
      motions is obtained. For these, different time scales are found, which allows the
      separation of nanosecond from microsecond conformational motions. In the
      simulations, rotation of the gamma-stalk lowers the ATP affinity of the betaTP
      binding pocket and triggers fast, spontaneous closure of the empty betaE subunit.
      The simulations explain several mutation studies and the reduced hydrolysis rate
      of gamma-depleted F1-ATPase.

PMID- 11836536
TI  - Dimeric structure of the Oxytricha nova telomere end-binding protein alpha
      subunit bound to ssDNA.
AB  - Telomeres are the specialized protein--DNA complexes that cap and protect the
      ends of linear eukaryotic chromosomes. The extreme 3' end of the telomeric DNA in
      Oxytricha nova is bound by a two-subunit sequence-specific and 3' end-specific
      protein called the telomere end-binding protein (OnTEBP). Here we describe the
      crystal structure of the alpha-subunit of OnTEBP in complex with T4G4 single
      stranded telomeric DNA. This structure shows an (alpha--ssDNA)2 homodimer with a
      large approximately 7,000 A2 protein--protein interface in which the domains of
      alpha are rearranged extensively from their positions in the structure of an
      alpha--beta--ssDNA ternary complex. The (alpha--ssDNA)2 complex can bind two
      telomeres on opposite sides of the dimer and, thus, acts as a protein mediator of
      telomere--telomere associations. The structures of the (alpha--ssDNA)2 dimer
      presented here and the previously described alpha--beta--ssDNA complex
      demonstrate that OnTEBP forms multiple telomeric complexes that potentially
      mediate the assembly and disassembly of higher order telomeric structures.

PMID- 11836537
TI  - The SIN domain of the histone octamer is essential for intramolecular folding of
      nucleosomal arrays.
AB  - The SIN domain within histones H3 and H4 is defined by a set of single amino acid
      substitutions that were initially identified as mutations that alleviate the
      transcriptional defects associated with inactivation of the SWI/SNF chromatin
      remodeling complex. Here we use recombinant histones to investigate how Sin-
      versions of H4 alter the structure of nucleosomal arrays. We find that an R45C
      substitution within the SIN domain of H4 does not disrupt nucleosome positioning
      nor does this Sin- version alter the accessibility of nucleosomal DNA. In
      contrast, we find that the R45C substitution eliminates Mg2+-dependent,
      intramolecular folding of the nucleosomal arrays. Our results suggest that Sin-
      versions of histones may alleviate the need for SWI/SNF in vivo by disrupting
      higher-order chromatin folding.

PMID- 11836538
TI  - Cataract surgery: expectations of patients assisted during a community project in
      Sao Paulo, state of Sao Paulo, Brazil.
AB  - OBJECTIVE: To identify social characteristics and expectations of individuals
      seen during a community project for the treatment of senile cataracts. Expected
      results from their eye surgery and its consequences to their quality of life were
      studied as well. METHODOLOGY: Cataract patients (visual acuity equal to or lower
      than 0.2 in the more superior eye) aged 50 years or over, were surveyed by means
      of interviews held during their visit at the Cataract Project in Sao Paulo city,
      State of Sao Paulo, Brazil, in 1999. RESULTS: The sample was composed of 331
      subjects of low socioeconomic level ranging in age from 50 to 97 years (average =
      71.8 years). Expectation of total recovery from the cataract condition by means
      of surgery was declared by 80.0% of the respondents, with no significant
      differences between male and female subjects (P < 0.1723). Hope to resume manual
      activities was expressed by 59.8%. CONCLUSION: A predominance of expectations of
      resuming normal activity and achieving a better quality of life after cataract
      surgery were identified.

PMID- 11836539
TI  - Conization, frozen section examination, and planned hysterectomy in the treatment
      of high-grade cervical intraepithelial neoplasia.
AB  - PURPOSE: We tested the role of frozen section examination of the cone specimen in
      the evaluation of the resection margin status and to rule out invasion in
      patients with high-grade cervical intraepithelial neoplasia. METHODS: Twenty-five
      patients with cervical intraepithelial neoplasia underwent conization followed by
      frozen section examination and planned hysterectomy. The results of the
      definitive paraffin exam were compared with frozen section examination. RESULTS:
      In the evaluation of the margins by frozen section examination, 16 patients (64%)
      had positive cone margins and 9 (36%) had negative margins. The definitive
      paraffin examination of margin status was concordant in all the cases.
      Intraoperative diagnosis of invasion was made in 5 cases, and 1 of these was
      microinvasive. Among the remaining 20 cases, we detected 2 additional
      microinvasive carcinomas after paraffin study, so the diagnosis of the frozen
      section examination was concordant with the paraffin sections in 23/25 cases
      (92%). Two cases of microinvasive carcinoma were diagnosed as cervical
      intraepithelial neoplasia by frozen section examination and had less than 2 mm
      stromal invasion. CONCLUSIONS: In high-grade cervical intraepithelial neoplasia,
      frozen section examination can provide immediate and precise evaluation of the
      cone margin status in high-grade cervical intraepithelial neoplasia. It can
      identify frank invasion and permit adequate treatment in a one-stage procedure.
      In early microinvasive disease, frozen section examination fails to detect the
      area of invasion but reliably detects clear resection margins.

PMID- 11836540
TI  - Heart hypoplasia in an animal model of congenital diaphragmatic hernia.
AB  - PURPOSE: In previous papers, we described a new experimental model of congenital
      diaphragmatic hernia in rabbits, and we also reported noninvasive therapeutic
      strategies for prevention of the functional and structural immaturity of the
      lungs associated with this defect. In addition to lung hypoplasia, pulmonary
      hypertension, biochemical, and structural immaturity of the lungs, the
      hemodynamics of infants and animals with congenital diaphragmatic hernia are
      markedly altered. Hence, cardiac hypoplasia has been implicated as a possible
      cause of death in patients with congenital diaphragmatic hernia, and it is
      hypothesized to be a probable consequence of fetal mediastinal compression by the
      herniated viscera. Cardiac hypoplasia has also been reported in lamb and rat
      models of congenital diaphragmatic hernia. The purpose of the present experiment
      was to verify the occurrence of heart hypoplasia in our new model of surgically
      produced congenital diaphragmatic hernia in fetal rabbits. METHODS: Twelve
      pregnant New Zealand rabbits underwent surgery on gestational day 24 or 25
      (normal full gestational time - 31 to 32 days) to create left-sided diaphragmatic
      hernias in 1 or 2 fetuses per each doe. On gestational day 30, all does again
      underwent surgery, and the delivered fetuses were weighed and divided into 2
      groups: control (non-surgically treated fetuses) (n = 12) and congenital
      diaphragmatic hernia (n = 9). The hearts were collected, weighed, and submitted
      for histologic and histomorphometric studies. RESULTS: During necropsy, it was
      noted that in all congenital diaphragmatic hernia fetuses, the left lobe of the
      liver herniated throughout the surgically created defect and occupied the left
      side of the thorax, with the deviation of the heart to the right side,
      compressing the left lung; consequently, this lung was smaller than the right
      one. The body weights of the animals were not altered by congenital diaphragmatic
      hernia, but heart weights were decreased in comparison to control fetuses. The
      histomorphometric analysis demonstrated that congenital diaphragmatic hernia
      promoted a significant decrease in the ventricular wall thickness and an increase
      in the interventricular septum thickness. CONCLUSION: Heart hypoplasia occurs in
      a rabbit experimental model of congenital diaphragmatic hernia. This model may be
      utilized for investigations in therapeutic strategies that aim towards the
      prevention or the treatment of heart hypoplasia caused by congenital
      diaphragmatic hernia.

PMID- 11836541
TI  - Recurrent spontaneous breast hematoma: report of a case and review of the
      literature.
AB  - BACKGROUND: Breast hematomas are common after traumas, surgeries, or contusions.
      They are rarely spontaneous, but they can occur spontaneously in patients with
      hematologic disease or with coagulation disorders. MATERIAL AND METHODS: The
      authors report a clinical case of a 48-year-old female with a 27-year history of
      paroxysmal nocturnal hemoglobinuria who underwent mammography screening because
      of a painless palpable moveable node in the upper inner quadrant of the right
      breast. RESULTS: Mammography showed a partially defined heterogeneous node of 35
      mm without microcalcifications in the upper inner quadrant of the right breast
      which, associated with the clinical features, seemed to be an hematoma. Further
      mammography and ultrasound after 45 days showed retrocession of the lesion, and
      another mammography obtained after 60 days was normal. Seventy-five days after
      the first episode, the patient complained of another node with a skin bruise in
      the upper outer quadrant of the same breast, which seemed to be a recurrent
      hematoma. Two months later the mammography obtained was normal. CONCLUSION:
      Breast hematoma must be thought of as a differential diagnosis for a breast node,
      regardless of previous trauma or hematologic disorders.

PMID- 11836542
TI  - Necrolytic migratory erythema associated with glucagonoma syndrome: a case
      report.
AB  - Necrolytic migratory erythema is a rare skin condition that consists of migrating
      areas of erythema with blisters that heal with hyperpigmentation. It usually
      occurs in patients with an alpha islet cell tumor of the pancreas-or glucagonoma
      and when associated with glucose intolerance, anemia, hyperglucagonemia, and
      weight loss defines the glucagonoma syndrome. We describe a 52-year-old female
      patient with necrolytic migratory erythema associated with glucagonoma syndrome
      who had metastatic disease at presentation and passed away one week after her
      admission. The autopsy showed a tumor in the body of the pancreas, which was
      diagnosed as a neuroendocrine tumor and confirmed by immunohistochemistry. The
      diagnosis of necrolytic migratory erythema is a matter of great importance, since
      it might be an auxiliary tool for the early detection of glucagonoma.

PMID- 11836543
TI  - Secondary hypogammaglobilinemia after use of carbamazepine: case report and
      review.
AB  - Immunologic disorders related to anticonvulsant therapy have been described in
      the last three decades, including cellular and humoral alterations that result in
      recurrent infections; however, the physiopathologic mechanisms are not completely
      understood. This report describes a patient with complex partial epilepsy and
      hypogammaglobulinemia while in treatment with carbamazepine, with significant
      improvement in clinical signs and laboratory tests after substitution to sodium
      valproate. The authors stress the importance of clinical and laboratory
      evaluation of patients in continuous anticonvulsant therapy, including
      immunoglobulins levels and peripheral blood evaluations.

PMID- 11836544
TI  - Switching diet from Egyptian pyramids to Amazonian fruits: changing our menu
      using epidemiological evidence.

PMID- 11836546
TI  - Impact of degenerative radiographic abnormalities and vertebral fractures on
      spinal bone density of women with osteoporosis.
AB  - CONTEXT: Measurements of bone density taken by dual-energy x-ray absorptiometry
      are the most accurate procedure for the diagnosis of osteoporosis. This procedure
      has the disadvantage of measuring the density of all mineral components,
      including osteophytes, vascular and extra vertebral calcifications. These
      alterations can influence bone density results and densitometry interpretation.
      OBJECTIVE: To correlate radiography and densitometry findings from women with
      osteoporosis, analyzing the influence of degenerative processes and vertebral
      fractures on the evaluation of bone density. DESIGN: Retrospective study.
      SETTING: Osteoporosis outpatients' clinic at Hospital das Clinicas, Universidade
      Estadual de Campinas. PARTICIPANTS: Ninety-six postmenopausal women presenting
      osteoporosis diagnosed by bone density. MAIN MEASUREMENTS: Bone mineral density
      of the lumbar spine and femoral neck were measured by the technique of dual
      energy x-ray absorptiometry, using a LUNAR-DPX densitometer. Fractures,
      osteophytes and aortic calcifications were evaluated by simple x-rays of the
      thoracic and lumbar spine. RESULTS: The x-rays confirmed vertebral fractures in
      41.6%, osteophytes in 33.3% and calcifications of the aorta in 30.2%. The
      prevalence of fractures and aortic calcifications increased with age. The mean
      bone mineral density was 0.783g/cm2 and the mean T-score was - 3.47 DP. Neither
      fractures nor aortic calcifications had significant influence on bone mineral
      density (P = 0.36 and P = 0.09, respectively), despite the fractured vertebrae
      having greater bone mineral density (P < 0.02). Patients with lumbar spine
      osteophytes showed greater bone mineral density (P = 0.04). Osteophytosis was
      associated with lumbar spine bone mineral density after adjustment for fractures
      and aortic calcifications by multiple regression (P = 0.01). CONCLUSION:
      Osteophytes and lumbar spine fractures can overestimate bone density
      interpretation. The interpretation of densitometry results should be carried out
      together with the interpretation of a simple lumbar spine x-ray in elderly women.

PMID- 11836547
TI  - Stethoscope: a friend or an enemy?
AB  - CONTEXT: The stethoscope is a universal tool in the hospital that is in direct
      contact with many patients and can therefore be a vector in the dissemination of
      bacterial infections. OBJECTIVE: To research the presence of bacteria, fungi and
      yeast on the stethoscope diaphragm and the resistance of bacteria to
      antimicrobial drugs. DESIGN: Descriptive, prospective, non-controlled. SETTING: A
      tertiary care hospital. SAMPLE: Samples were taken randomly from 300 stethoscopes
      employed by medical staff (medical residents, medical students, nurses and
      nursing school students) and other sectors of the hospital. MAIN MEASUREMENTS:
      Three hundred stethoscope diaphragms used in several sectors of the hospital
      facilities by medical doctors (63 samples), medical residents (54 samples),
      medical students (106 samples), nursing school students (33 samples) and specific
      sectors (36 samples) were analyzed. Material was collected randomly. It was
      collected with the aid of a sterile swab moistened in physiological solution,
      inoculated into Brain Heart Infusion media and incubated in an oven for 24 to 48
      hours. After this period, the samples were inoculated into blood agar, MacConkey
      agar and Sabouraud media and identified by Gram staining and biochemical assays.
      An assay to test bacteria sensitivity to antibiotics was also carried out by the
      Kirby-Bauer method. RESULTS: Eighty-seven percent of the analyzed stethoscopes
      were contaminated. Gram-positive cocci, yeasts, fungi and Gram-positive and
      negative bacilli were isolated. There was no significant association between the
      most predominant microorganisms and professional category. Staphylococcus aureus,
      Staphylococcus negative coagulase and Bacillus were significantly more frequent
      in relation to the presence of more than one microorganism on the stethoscope
      diaphragm. CONCLUSION: Stethoscopes presented a high rate of contamination and
      their use without precautions can spread nosocomial infections.

PMID- 11836548
TI  - Sydenham's chorea--clinical and evolutive characteristics.
AB  - CONTEXT: During the last 12 years we have observed an increase in the frequency
      of Sydenham's chorea in our country. We have observed that some of our patients
      have presented recurrence of the chorea despite regular treatment with benzathine
      penicillin. OBJECTIVE: The aim of our study was to evaluate clinical and
      evolutive characteristics of Sydenham's chorea in a group of patients followed in
      our Pediatric Rheumatology Unit. TYPE OF STUDY: Retrospective study. SETTING:
      Section of Pediatric Rheumatology - Discipline of Allergy, Clinical Immunology
      and Rheumatology - Department of Pediatrics - UNIFESP - EPM. PARTICIPANTS: Two
      hundred and ninety patients with rheumatic fever followed between 1986 and 1999.
      METHODS: We reviewed the records of 290 patients with rheumatic fever followed
      between 1986 and 1999. All patients were diagnosed according to the revised Jones
      criteria (1992). We included 86 patients that presented Sydenham's chorea as one
      of the major criteria (one or more attacks) and evaluated their clinical and
      evolutive characteristics as well the treatment. RESULTS: Fifty-five patients
      were girls and 31 were boys. The mean age at onset was 9.7 years and mean follow
      up period was 3.6 years. The 86 Sydenham's chorea patients presented 110 attacks
      of chorea. We observed isolated chorea in 35% of the patients, and 25 (29%)
      presented one or more recurrences. We included only 17 of the 25 patients for
      further analysis, with a total of 22 recurrences of which 14 were attacks of
      chorea, because it was not possible to precisely detect the interval between
      attacks in the other patients. The approximate interval between the attacks
      ranged from 4 to 96 months. In 71% of the patients there was no failure in the
      secondary prophylaxis with benzathine penicillin, which was performed every 3
      weeks. CONCLUSION: Despite the regular use of secondary benzathine penicillin
      prophylaxis, children with rheumatic fever have a high risk of Sydenham's chorea
      recurrence.

PMID- 11836545
TI  - Normal erythrocyte calpain I activity on membrane proteins under near
      physiological conditions in patients with essential hypertension.
AB  - CONTEXT: It has been reported that the equilibrium between the erythrocyte
      protease calpain I and its physiological inhibitor calpastatin is disrupted in
      patients with essential hypertension. OBJECTIVE: To investigate the activity of
      non-purified calpain I in hemolysates against the erythrocytic membrane proteins,
      rather than against other substrates. DESIGN: Evaluation of calpain I red cell
      activity upon its own physiological substrates in hypertensive patients, in a
      near-physiological environment. SETTING: LIM-23 and LIM-40 of Hospital das
      Clinicas of the Faculty of Medicine of USP. SAMPLE: Patients with moderate
      primary hypertension over 21 years of age who were given amlodipine (n:10) and
      captopril (n:10) for 8 weeks, plus normal controls (n:10). MAIN MEASUREMENTS: Red
      cell membrane proteins were incubated with and without protease inhibitors and
      with and without calcium chloride and underwent polyacrylamide gel
      electrophoresis. RESULTS: Digestion of bands 2.1 and 4.1 was observed, indicating
      calpain I activity. No statistical differences regarding bands 2.1 and 4.1 were
      observed before treatment, between the controls and the hypertensive patients,
      either in ghosts prepared without calcium or with increasing concentrations of
      calcium. Nor were statistical differences observed after treatment, between the
      controls and the patients treated with amlodipine and captopril, or between the
      patients before and after treatment with both drugs. CONCLUSION: The final
      activity of non-purified calpain I upon its own physiological substrate, which
      was the approach utilized in this study, may more adequately reflect what happens
      in red cells. Under such conditions no imbalance favoring calpain I activity
      increase was observed. The protective factor provided by calpastatin against
      calpain I activity may diminish under hypertension.

PMID- 11836549
TI  - Analysis of the p53 gene and papillomavirus detection in smears from cervical
      lesions.
AB  - CONTEXT: Alterations of the p53 tumor suppressor gene are correlated with a
      critical step in the development of many human cancers. The tumor suppressor gene
      functions include regulation of the cell cycle and the cellular response to DNA
      damage, initiation of DNA repair and replication, induction of apoptosis and
      promotion of cell differentiation. CASE REPORT: Smears from ten cases of cervical
      lesions were analyzed for status of exons 5-8 of the p53 gene using PCR/SSCP. HPV
      infection was also screened by the PCR method using two PCR primer sets. Changes
      in the p53 gene were observed in a case of squamous carcinoma and a case of
      asymptomatic cervical intraepithelial neoplasia grade III (CIN III). High-risk
      HPV was detected in both cases showing that HPV infection and p53 mutation are
      not exclusive events.

PMID- 11836550
TI  - Familial association of pseudohypoparathyroidism and psoriasis: case report.
AB  - CONTEXT: The association between psoriasis and hypoparathyroidism has been
      reported by several authors, and it has been suggested that abnormalities in
      calcium homeostasis may be involved in the development or exacerbation of
      psoriasis. However, so far there have only been two reports of
      pseudohypoparathyroidism associated with psoriasis. OBJECTIVE: To describe the
      familial occurrence of this association for the first time. CASE REPORTS: Two
      siblings with psoriasis associated with pseudohypoparathyroidism were presented.
      The first patient was a 24-year-old white male with disseminated erythrodermic
      pustular psoriasis that began 2 months before admission. He had had a history of
      mental retardation, recurrent otitis, seizures and arthralgia from the age of 11
      years onwards. He presented the characteristic phenotype of Albright
      osteodystrophy: short stature, obesity, round facies, broad forehead, short neck
      and brachydactylia. He adopted a position of flexed limbs and showed proximal
      muscle weakness and a positive Trousseau sign. He had clinical signs of
      hypocalcemia (0.69 mmol/l ionized calcium and 3.2 mg/dl total calcium),
      hyperphosphatemia (6.6 mg/dl), hypomagnesemia (1.0 mEq/l), hypoalbuminemia (3.1
      g/dl), normal serum intact PTH levels (45.1 pg/ml), primary hypothyroidism (13.2
      mU/ml TSH, and 4.7 mg/dl total T(4)), hypergonadotrophic hypogonadism (116.0
      ng/ml LH, 13.2 mU/ml FSH and 325.0 ng/dl testosterone), osteoporosis, and diffuse
      calcifications in soft tissues and in the central nervous system. The second case
      was a 14-year-old white girl with a history of psoriasis vulgaris from the age of
      five years onwards, and antecedents of mental retardation. She presented signs of
      Albright osteodystrophy (short stature, round facies, obesity, short neck,
      brachydactylia), hypocalcemia (ionized calcium of 1.08 mmol/l and total calcium
      of 6.7 mg/dl) hyperphosphatemia (9.4 mg/dl), elevated serum PTH levels (223.0
      pg/ml), osteoporosis, and hypergonadotrophic hypogonadism (7.0 mU/ml LH, 9.3
      mU/ml FSH and undetectable estradiol levels).

PMID- 11836551
TI  - Synchronous advanced gastric adenocarcinoma and advanced esophageal squamous cell
      carcinoma.
AB  - CONTEXT: Synchronous associations of esophageal and gastric cancers are not a
      common finding, especially with differing histological types and both tumors in
      advanced forms. A case with such an association is presented, in which an unusual
      therapy was proposed: palliative gastrectomy and esophageal intubation. CASE
      REPORT: A 75-year-old white man was referred to our service complaining of
      malaise and weight loss for one year and dysphagia and vomiting for 2 months. The
      patient had sought out medical consultation as a result of the latter two
      complaints.

PMID- 11836552
TI  - Laparoscopic drama.

PMID- 11836554
TI  - Down-regulated p16 expression predicts poor prognosis in patients with
      extrahepatic biliary tract carcinomas.
AB  - The prognosis of extrahepatic biliary tract cancer (EBT) patients is generally
      accepted to be poor. We immunohistochemically evaluated expression of p16, a
      cyclin-depend kinase inhibitor, in tumor specimens surgically removed from 99 EBT
      patients. We also examined whether there was any relationship between expression
      of p16 and biological malignancy of the tumor by comparing its
      clinicopathological factors. Consequently, we found that there were three types
      of p16 expression in the tumor cells; diffuse, heterogeneous and negative types,
      the percentages of which were 19, 41 and 39%, respectively. Heterogeneous and
      negative types, whose expression of p16 was considered to be down-regulated,
      showed scirrhous (p=0.022) and infiltrating growth (p=0.002). In addition, we
      found that the proportion of down-regulated expression of p16 was different,
      depending on the location of the tumor. We also observed that the down-regulated
      p16 expression was the highest in a proportion of patients with the extrahepatic
      bile duct carcinoma. In contrast, the proportion of down-regulated p16 expression
      was the least among the patients in the region of the ampulla of Vater with
      better prognosis, and we showed that the prognosis of patients with down
      regulated expression of p16 was the poorest in terms of the cancer location where
      it is limited to the region of ampulla of Vater. These findings suggest that down
      regulated p16 expression is evaluated as a factor of poorer prognosis and also
      that immunohistochemical pattern of p16 expression becomes a marker reflecting
      the biological malignancy of EBT patients.

PMID- 11836553
TI  - Expression analysis of pediatric solid tumor cell lines using oligonucleotide
      microarrays.
AB  - We identified patterns of differentially-expressed genes in cell lines derived
      from several pediatric solid tumors. Affymetrix Human Cancer G110 Arrays,
      carrying 1,700 cancer-associated genes, were applied to a panel of 11 cell lines
      originating from Ewing tumors (ETs), neuroblastomas, and malignant melanoma of
      soft parts. Hierarchical clustering clearly differentiated these 3 entities and
      revealed groups of 75, 102, and 36 gene probe-sets exhibiting tumor-type specific
      up-regulation in these cell lines, respectively. Whereas ET lines demonstrated
      increased expression of microtubule-associated protein tau (MAPT), protein
      phosphatase 1 regulatory subunit 1A (PPP1R1A), NIMA (never in mitosis gene a)
      related kinase 2 (NEK2), and cyclin D1 (CCND1), neuroblastoma samples exhibited
      high expression of wingless-type mouse mammary tumor virus integration site
      family member 11 (WNT11), Drosophila frizzled homolog 2 (FZD2), and adenomatous
      polyposis coli (APC) which are involved in regulating free beta-catenin levels.
      These genes likely maintain tumor-specific characteristics and participate in key
      downstream regulatory mechanisms. We also correlated the expression levels of up
      regulated genes in ETs with their chromosomal localization and compared these
      data to the comparative genomic hybridization profiles of the cell lines. We
      demonstrate that gains of genetic material contribute essentially to differential
      gene expression.

PMID- 11836555
TI  - Immunohistochemistry of cyclin D1 and beta-catenin, and mutational analysis of
      exon 3 of beta-catenin gene in parathyroid adenomas.
AB  - Parathyroid adenomas are benign uniglandular tumors and are the most common cause
      of primary hyperparathyroidism. Several genetic changes in parathyroid tumors,
      including inactivation of tumor suppressor genes, activation of oncogenes and
      loss of heterozygosity at several chromosomal loci, have been reported. In this
      study, we analyzed the status of cyclin D1 and beta-catenin in 24 cases of
      parathyroid adenoma. Immunohistochemistry of cyclin D1 showed positive staining
      in 9 (37.5%) of the 24 parathyroid adenomas. The status of beta-catenin, which
      has recently been identified as a regulator of cyclin D1 transcription, was
      examined by direct sequencing of exon 3 of the beta-catenin gene and
      immunohistochemistry of beta-catenin protein, but neither mutation nor
      accumulation of beta-catenin was detected in any of the cases. These results
      indicate that cyclin D1 is frequently accumulated in parathyroid adenomas,
      independently of dysfunction in the Wnt signaling pathway.

PMID- 11836556
TI  - Genome wide detection of oncogene amplifications in nasopharyngeal carcinoma by
      array based comparative genomic hybridization.
AB  - We have applied the method of genomic microarray to investigate amplification of
      oncogenes throughout the genome of nasopharyngeal carcinoma (NPC). Array based
      comparative genomic hybridization (array CGH) allows simultaneous examination of
      58 oncogenes commonly amplified in various human cancers. In the present study,
      we have examined 15 NPC samples including five cell lines, two xenografts and
      eight primary tumours with array CGH to reveal the particular oncogenes
      associated with this cancer. This is the first genome wide survey of multiple
      oncogene amplifications involved in the development of NPC. Non-random gene
      amplifications were identified for the first time in NPC on MYCL1 in 1p34.3 and
      on TERC and PIK3CA at 3q26.3. Other high level amplified oncogenes included NRAS,
      RAF1, MYB, EGFR, FGF4, EMS1, and D17S167. Highest frequencies of gain of novel
      oncogenes were detected on MYCL1 (66.7%), TERC (46.7%), ESR (46.7%), PIK3CA
      (40%), LAMC2 (33.3%), and CSE1L (33.3%).

PMID- 11836557
TI  - Establishment and characterization of a schwannoma cell line from a patient with
      neurofibromatosis 2.
AB  - By using retroviral mediated gene transfer technique, a primary schwannoma
      culture from a 56-year-old Neurofibromatosis type 2 (NF2) patient was
      immortalized with HPV E6-E7 genes. This cell line, HEI193, has a unique splice
      site mutation of the NF2 gene. Both immunocytochemistry and molecular biology
      techniques were used to demonstrate that this cell line is of Schwann cell
      origin. Comparison of the primary tumor with HEI193 revealed the same NF2
      mutation and an identical pattern of allele loss at multiple loci, indicating
      that the established cell line had maintained many of the properties of the
      original tumor. The immortalized cell line was non-tumorigenic in both severe
      combined immunodeficient (SCID) mice and nude mice, but has altered growth
      properties such as higher proliferation rate and independence of Schwann cell
      growth factors. To our knowledge, this is the first attempt to establish
      permanent cell lines from human NF2 patients. This Schwann tumor-derived cell
      line may provide a useful model system for the study of familial NF2 tumor
      pathogenesis, for elucidating NF2 functions and for testing new gene-based
      therapeutic approaches.

PMID- 11836558
TI  - Detection of axillary lymph node metastases in breast cancer with Tc-99m
      tetrofosmin scintigraphy.
AB  - The most important prognostic factor in breast (B) cancer (C) is axillary (A)
      lymph (L) node (N) status, and virtually all patients with BC undergo ALN
      dissection to assess N involvement. The aim of this study was to evaluate the
      accuracy of planar and tomographic Tc-99m tetrofosmin scintigraphy in the
      detection of ALN involvement in BC. A group of 85 female patients (age range: 31
      82 years) with 87 BCs were studied before surgery. Three planar images, right and
      left prone lateral and supine anterior thoracic views, and 360 degrees supine
      thoracic single photon emission tomography (SPET) were acquired after Tc-99m
      tetrofosmin injection (740 MBq i.v.). ALN status was evaluated by histological
      exam after A dissection: metastatic ALN involvement was proved in 31 out of 87
      cases. Sensitivity was 87.1% (27/31) for SPET and 61.3% (19/31) for planar images
      (p<0.01); specificity was 92.9% (52/56) and 94.6% (53/56), respectively, with a
      global accuracy of 90.8% (79/87) for SPET and 82.8% (72/87) for planar imaging
      (p<0.05). Sensitivity rose from 75% in non-palpable Ns to 94.7% in palpable ones
      for SPET, and from 41.7 to 73.7% for planar scans. SPET was positive in 17/18
      (94.4%) patients with >3 metastatic Ns and in 10/13 (76.9%) with < or = 3
      involved Ns, whereas planar images were positive in 14/18 (77.8%) and in 5/13
      (38.5%) cases, respectively. In conclusion, our findings indicate that Tc-99m
      tetrofosmin scintigraphy is useful in the presurgical detection of ALN metastases
      in BC, with SPET more accurate than conventional planar images, thus suggesting
      its more frequent use in scintimammography; moreover, the total number of
      histologically involved Ns can affect the scintigraphic results.

PMID- 11836559
TI  - Karyotypic variation between independently cultured strains of the cell line MCF
      7 identified by multicolour fluorescence in situ hybridization.
AB  - The breast cancer cell line MCF-7 is a widely used model in breast cancer
      research however a number of conflicting reports have been published regarding
      its biological properties. We hypothesised that there will be significant in
      vitro mutation and genotypic evolution over time in this cell line. To assess the
      genetic divergence of MCF-7 at the chromosomal level, we analysed MCF-7 cell
      lines grown independently at three different laboratories using M-FISH and CGH.
      In addition, MCF-7 cells from our own laboratory were also analysed at two time
      points 18 months apart. Several common chromosomal translocations were identified
      in all variants of the cell lines. In addition, a significant number of unique
      abnormalities were identified, characterising each of the variants studied.
      Genotypic differences between cell lines grown independently in different
      laboratories would significantly alter the phenotypic characteristics of each
      cell line rendering biological properties inconsistent between laboratories.

PMID- 11836560
TI  - Immunohistochemical pattern of cytokeratins and MMPs in human keratinocyte cell
      lines of different biological behaviour.
AB  - We investigated three clonally related human keratinocyte cell lines of different
      biological behaviour, HaCaT (non-tumorigenic), A5 (benign, tumorigenic) and II
      4RT (malignant, tumorigenic), with regard to the cell-associated localization of
      the major MMPs -1, -2, -3, -9, -10 and -11. These observations were correlated
      with the pattern of cytokeratins (CK) 10, 13 and 14 which served as markers for
      cellular. In all three cell lines, we detected immunohistochemically various MMPs
      within the cytoplasm of the tumor cells, however, with differences between the
      MMPs and the various cell lines. MMP-1, -10 and -11 were strongly and equally
      present in all cell lines tested. MMP-2 was seen only faintly in all cells. In
      contrast, MMP-3 was only faintly seen in the cytoplasm of the non-tumorigenic,
      more extensive in the benign A5 cells, but strongly and extensive in the
      malignant II-4RT cells. MMP-9 was also seen in increasing intensity corresponding
      to the tumorigenicity of the three cells lines, however, with less intense
      staining than MMP-3. A semiquantitative immunoreactive score confirmed these
      observations. In parallel, the CK pattern indicated advanced cellular maturation
      of HaCaT (as seen by expression of basal CK 14 and suprabasal CKs 10 and 13). In
      the A5 cells a reduced expression of suprabasal CKs-10 and -13 indicated lesser
      maturation. The malignant II-4RT cells revealed even fewer cells with suprabasal
      keratinocyte differentiation. Our study clearly confirms differences in the
      concentration of cell-associated MMPs. These analyses parallel and supplement our
      previous biochemical studies. In addition, we provide circumstantial evidence
      that the expression of several major MMPs is associated with changes in the
      maturation pattern as evidenced by expression of CKs.

PMID- 11836561
TI  - Suppression subtractive hybridisation to isolate differentially expressed genes
      involved in invasiveness of melanoma cell line cultured under different
      conditions.
AB  - We have previously analysed the invasion capacity of different melanoma cell
      lines in the three-dimensional dermal equivalent. The melanoma cell line M4Beu
      acquired invasive behaviour upon changing its cultivation conditions before the
      seeding on top of the collagen lattice from single cell suspension to spheroid.
      Based on this phenomenon SSH was used to search for the genes related to the
      invasive phenotype of melanoma cells. From differentially expressed clones we
      focused on four: fibronectin, RhoA, COXII, and H-ras-like protein. By RT-PCR the
      expression of these genes were tested in different populations (monolayer,
      spheroids on dermal equivalent) of melanoma cell line M4Beu and three additional
      melanoma cell lines. The expression of fibronectin was also examined by
      immunohistochemistry staining of co-culture spheroids-dermal equivalent.

PMID- 11836562
TI  - Plasma vascular endothelial growth factor is useful in assessing progression of
      breast cancer post surgery and during adjuvant treatment.
AB  - Vascular endothelial growth factor (VEGF) has been shown to induce angiogenesis
      in vivo and in vitro. However, the association of plasma VEGF with tumor
      histopathology in high risk groups such as African American and non-white
      Hispanic women with breast cancer is not well understood. There is limited
      information on the prognostic relevance of plasma VEGF in patients who have had
      surgery and adjuvant treatment for breast cancer. In this study, we measured
      plasma VEGF from 125 minority women with primary breast tumor removal and were
      completing adjuvant treatment. The control group consisted of 20 subjects without
      cancer. We examined the association between plasma VEGF and other tumor
      characteristics such as steroid hormone receptors, tumor size, regional nodes,
      stage, recurrence, and overall survival. Our results confirmed that plasma VEGF
      levels were significantly higher in breast cancer patients than normal subjects.
      Plasma VEGF level increased in patients with increase in tumor size, and at late
      stage III/IV disease. Univariate analysis showed plasma VEGF to be a significant
      predictor of overall survival (RR=2.5, p=0.02). Multivariate analysis showed
      plasma VEGF not only to be an independent predictor of overall survival (RR=4.6,
      p=0.02) but also of local recurrence (RR=6.0, p=0.04). Tamoxifen in combination
      with CMF or CAF can reduce plasma VEGF level in patients with estrogen receptor
      positive tumor but not in estrogen receptor negative tumor. Our findings suggest
      that plasma VEGF should be considered as a tumor marker for breast cancer
      progression, and inhibitors of angiogenesis should be factored into the treatment
      protocol for patients who demonstrate increase in plasma VEGF levels at any stage
      of the disease.

PMID- 11836564
TI  - Infrequent mutations of the activating transcription factor-2 gene in human lung
      cancer, neuroblastoma and breast cancer.
AB  - The activating transcription factor 2 (ATF-2) gene, which encodes a transcription
      factor involved in multiple intracellular signal transduction pathways, is
      located on human chromosome 2q32, which is a common region of LOH in human lung
      cancer. In neuroblastoma and breast cancer, a high incidence of LOH was detected
      on chromosome 2q. Recently we found that breast cancer is frequently developed in
      heterozygous mutant mice for the ATF-2 gene. Therefore, the ATF-2 gene was
      considered as a candidate tumor suppressor gene on 2q. To assess the role of the
      ATF-2 gene as a tumor suppressor in human carcinogenesis, we examined genetic
      alterations of the ATF-2 gene in 9 breast cancer cell lines, 10 neuroblastoma
      cell lines and 46 lung cancer cell lines. For this purpose, we first determined
      the exon-intron structure of the ATF-2 gene in the human genome. The ATF-2 gene
      was composed of 14 exons and 13 introns, and the ATG start codon and the TGA stop
      codon were present in exons 3 and 14, respectively. Genetic variants of the ATF-2
      gene were detected in 5 of the 46 (10.6%) lung cancers, but not in neuroblastomas
      and breast cancers. Three of the five variants detected in lung cancers were
      genetic polymorphisms, while the remaining two, consisting of non-synonymous and
      synonymous substitutions, were possibly somatic mutations. The present result
      indicates that the ATF-2 gene is not a major tumor suppressor gene on chromosome
      2q, however, it is possible that ATF-2 alterations may be involved in the
      development of a small subset of lung cancers.

PMID- 11836563
TI  - The effect of adjuvant 5'-deoxy-5-fluorouridine in early stage breast cancer
      patients: results from a multicenter randomized controlled trial.
AB  - To assess the efficacy of 5'-DFUR, an intermediate of capecitabine, for adjuvant
      treatment of early breast cancer, we conducted an open-labeled multi-center
      randomized controlled trial to compare postoperative 5'-DFUR treatment with
      surgery alone. We enrolled 1217 primary breast cancer patients and randomly
      assigned them into two treatment groups; one received six-month postoperative 5'
      DFUR treatment by consecutive or intermittent administration, and the other
      surgery alone. Follow-up surveys were conducted once a year for all subjects
      simultaneously and examined their outcome/presence or absence of the cancer
      recurrence. The central study committee reviewed all follow-up data and judged
      the recurrence data to be used for the analysis. Eight-year follow-up data showed
      no significant differences in relapse-free and overall survival between the two
      groups, and 5'-DFUR treatment regimen showed an extremely high tolerance.
      Possible explanations are discussed for the finding of no significant survival
      difference between adjuvant 6-month 5'-DFUR monotherapy and surgery alone in
      early breast cancer.

PMID- 11836565
TI  - The induction of apoptosis by a combined 1,25(OH)2D3 analog, EB1089 and TGF-beta1
      in NCI-H929 multiple myeloma cells.
AB  - Previously, we reported that EB1089 inhibited the growth of NCI-H929 myeloma
      cells via cell cycle arrest and apoptosis. In the present study, we investigated
      whether a combined EB1089 and TGF-beta1 synergistically inhibited the cell
      proliferation of myeloma cell lines. While TGF-beta1 alone could not inhibit the
      proliferation of any of the tested myeloma cells, synergistic effect between
      EB1089 (1 x 10(-8) M) and TGF-beta1 (1 ng/ml) was observed in NCI-H929 cells. TGF
      beta1 intensified the decreased expression of CDK2, CDK4, CDK6 and cyclin D1 in
      EB1089-treated NCI-H929 cells. However, these effects did not intensify to
      decrease CDK2 activity of EB1089-treated NCI-H929 cells, resulting in no
      difference in the extent of G1 arrest between EB1089- and both agents-treated
      cells. Remarkably, both agents synergistically induce apoptosis of NCI-H929
      cells, which was accompanied with up-regulation of Bax, degradation of PARP and
      Rb proteins, and loss of mitochondrial transmembrane potential (deltapsim).
      EB1089 caused the induction of SMAD4, a mediator of TGF-beta1 signaling. In
      addition, a combined EB1089 and TGF-beta1 increased p21 and JNK/SAPK activity
      whereas neither EB1089 nor TGF-beta1 affected p21 and JNK/SAPK activity. Taken
      together, these results suggest that treatment with both EB1089 and TGF-beta1
      synergistically inhibits the proliferation of NCI-H929 cells through apoptosis.

PMID- 11836566
TI  - Cadmium-induced neoplastic transformation of human prostate epithelial cells.
AB  - Cadmium is a ubiquitous environmental human carcinogen. Epidemiological and
      animal studies have suggested its carcinogenic potential on the prostate. In the
      present study, non-tumorigenic human prostate epithelial cells (pRNS-1-1)
      immortalized by simian papovavirus (SV40) were transformed after repeated
      exposures to cadmium. Such transformants showed morphological alterations,
      anchorage-independent growth in soft agar, and formed tumors when transplanted
      into SCID mice. The tumors were characterized histologically as poorly
      differentiated adenocarcinomas, expressing prostate-specific antigen (PSA),
      androgen receptor (AR), prostate stem cell antigen (PSCA), NKX3.1 and cytokeratin
      8 (CK8). These findings provide evidence of malignant transformation of human
      prostate epithelial cells exposed to this environmentally important chemical.

PMID- 11836567
TI  - Mechanism(s) of antitumor action in protracted infusion of low dose 5
      fluorouracil and cisplatin in gastric carcinoma.
AB  - The therapeutic efficacy of low dose administration of 5-fluorouracil (5-FU) and
      cisplatin (CDDP) (low dose FP) has been reported in patients with advanced and
      recurrent gastric carcinoma. Mechanism(s) by which low dose FP exerts antitumor
      effect is not entirely clear. We investigated mechanism(s) of the therapeutic
      efficacy in combination with 5-FU and CDDP in terms of signal transduction
      pathways leading to apoptosis. Using two human gastric carcinoma cell lines,
      MKN28 and MKN45, antitumor effect in combination treatment with 5-FU and CDDP was
      assessed by MTT 5-day assay. The significant antitumor effect was determined with
      more than 50% growth inhibition compared to control cells. Enhancement of
      antitumor effect in the combination treatment was analyzed using isobologram.
      Apoptotic cell death was assessed by DNA ladder formation assay, and expression
      of apoptosis-related genes was detected by Western blotting. Concentration of
      free platinum and 5-FU was measured by high-pressure liquid chromatography
      (HPLC), and dihydropyrimidine dehydrogenase (DPD) activity and total folate
      levels were assessed by enzyme immunoassays. Antitumor effect in single treatment
      with 5-FU was not observed significantly with the concentration from 1 to 5
      microM in vitro. In contrast, antitumor effect in combination treatment with 5-FU
      and CDDP showed a synergism with the concentration of CDDP from 1.5 to 3 microM.
      Single treatment with CDDP also did not show significant antitumor effect with
      the concentration from 1.5 to 3 microM. The enhancement in the synergistic effect
      by CDDP was dose-dependent. Any free platinum treated with low dose CDDP was not
      detected into gastric carcinoma cells, however, treatment with CDDP induced a
      receptor signaling pathway, that is mediated by Fas but not DR4. It may directly
      activate caspase 3 leading to apoptosis. Although the receptor signaling pathway
      in apoptosis was not observed by 5-FU, Bax-induced cytochrome c and caspase 3 was
      also observed in a receptor-independent pathway by 5-FU and CDDP. Total folate
      levels by cotreatment with CDDP was increased to 1.5-fold compared to 5-FU alone,
      whereas DPD activity and 5-FU concentration were not changed by cotreatment of
      CDDP in vivo. The enhancement of antitumor effect by low dose FP can be explained
      as follows: i) low dose treatment with CDDP induces apoptotic cell death through
      a receptor signaling pathway even in absence of free platinum into cells; ii)
      increased folate level by CDDP and a non-receptor signaling pathways by 5-FU
      contribute to apoptotic cell death in gastric carcinoma.

PMID- 11836568
TI  - Cyclooxygenase-2 expression influences the growth of human large and small cell
      lung carcinoma lines in athymic mice: impact of an organoselenium compound on
      growth regulation.
AB  - Increased expression of cyclooxygenase-2 (COX-2) significantly enhances
      carcinogenesis and inflammatory reactions. Regulation of COX-2 overexpression may
      be a reasonable target for cancer chemoprevention. We have tested the hypothesis
      that levels of COX-2 expression determine the growth of human lung cancer cells
      in nude mice. Two cell lines, NCI-H460 (non-small cell lung cancer) and NCI-H69
      (small cell lung cancer) were selected because the former expresses high levels
      of COX-2 protein and the latter has no detectable levels. We also examined the
      effects of 1,4-phenylenebis(methylene)selenocyanate (p-XSC), a highly effective
      chemopreventive organoselenium compound and known inhibitor of COX-2 expression,
      in vivo, on cell growth and COX-2 expression in vitro in the NCI-H460 cancer cell
      line. Cells were exposed to p-XSC at levels between 10 and 100 microM for six
      days and showed toxicity at approximately 50 microM. Pre-exposure of NCI-H460 to
      non-toxic levels of p-XSC suppressed COX-2 protein expression in a dose-dependent
      manner. At 40 microM, p-XSC suppressed phorbol myristate acetate (PMA)-induced
      COX-2 expression in NCI-H460 cells by more than 66%. In vivo studies in athymic
      mice showed a significant difference in tumor volume between cell lines. Pre
      treatment of NCI-H460 cells with a non-toxic dose of p-XSC, prior to their
      injection into nude mice, significantly suppressed tumor growth when compared to
      untreated cells. Collectively, the outcome of our in vitro and in vivo studies
      supports the hypothesis that levels of COX-2 expression determine the extent of
      human lung tumor growth in athymic mice. Therefore, inhibition of COX-2
      expression by agents such as p-XSC provides a strong rationale for the
      development of future clinical prevention trials.

PMID- 11836569
TI  - Fermented wheat germ extract induces apoptosis and downregulation of major
      histocompatibility complex class I proteins in tumor T and B cell lines.
AB  - The fermented wheat germ extract (code name: MSC, trade name: Avemar), with
      standardized benzoquinone content has been shown to inhibit tumor propagation and
      metastases formation in vivo. The aim of this study was to understand the
      molecular and cellular mechanisms of the anti-tumor effect of MSC. Therefore, we
      have designed in vitro model experiments using T and B tumor lymphocytic cell
      lines. Tyrosine phosphorylation of intracellular proteins and elevation of the
      intracellular Ca2+ concentration were examined using immunoblotting with anti
      phosphotyrosine antibody and cytofluorimetry by means of Ca2+ sensitive
      fluorescence dyes, Fluo-3AM and FuraRed-AM, respectively. Apoptosis was measured
      with cytofluorimetry by staining the DNA with propidium iodide and detecting the
      cell population. The level of the cell surface MHC class I molecules was analysed
      with indirect immunofluorescence on cytofluorimeter using a monoclonal antibody
      to the non-polymorphic region of the human MHC class I. MSC stimulated tyrosine
      phosphorylation of intracellular proteins and the influx of extracellular Ca2+
      resulted in elevation of intracellular Ca2+ concentration. Prominent apoptosis of
      20-40% was detected upon 24 h of MSC treatment of the cell lines. As a result of
      the MSC treatment, the amount of the cell surface MHC class I proteins was
      downregulated by 70-85% compared to the non-stimulated control. MSC did not
      induce a similar degree of apoptosis in healthy peripheral blood mononuclear
      cells. Inhibition of the cellular tyrosine phosphatase activity or Ca2+ influx
      resulted in the opposite effect increasing or diminishing the Avemar induced
      apoptosis as well as the MHC class I downregulation, respectively. A benzoquinone
      component (2,6-dimethoxi-p-benzoquinone) in MSC induced similar apoptosis and
      downregulation of the MHC class I molecules in the tumor T and B cell lines to
      that of MSC. These results suggest that MSC acts on lymphoid tumor cells by
      reducing MHC class I expression and selectively promoting apoptosis of tumor
      cells on a tyrosine phosphorylation and Ca2+ influx dependent way. One of the
      components in MSC, 2,6-dimethoxi-p-benzoquinone was shown to be an important
      factor in MSC mediated cell response.

PMID- 11836570
TI  - Molecular cloning and characterization of human GIPC2, a novel gene homologous to
      human GIPC1 and Xenopus Kermit.
AB  - PDZ-domain protein GIPC1/GIPC interacts with GTPase-activating protein RGS-GAIP,
      TGFbeta type III receptor, and integrin alpha6A subunit. Kermit, a Xenopus
      orthologue of human GIPC1, interacts with some class of WNT receptor. In this
      study, we identified a novel GIPC1-related gene in human genome by using
      bioinformatics, and isolated GIPC2 cDNAs by using cDNA-PCR. GIPC2 encoded a 315
      amino-acid protein with a central PDZ domain, which showed 62.0% total-amino-acid
      identity with GIPC1. Both GIPC2 gene on human chromosome 1 and GIPC1 gene on
      human chromosome 19p13.1 were found to consist of 6 exons. Exon-intron structures
      of GIPC2 gene and GIPC1 gene were well conserved. GIPC2 mRNA was relatively
      highly expressed in ascending colon, followed by kidney and pancreas. Among 3.7-,
      2.6-, and 1.7-kb GIPC2 mRNAs generated due to alternative polyadenylation, 2.6-kb
      GIPC2 mRNA was the major GIPC2 transcript in adult kidney. Expression of GIPC2
      mRNA was significantly down-regulated in 6 out of 14 cases of primary kidney
      tumors, in 5 out of 11 cases of primary colon tumors, and in 1 out of 7 cases of
      primary rectal tumors. Because GIPC2 might bind to TGFbeta type III receptor or
      some class of WNT receptor, just like GIPC1 or Kermit, down-regulation of GIPC2
      mRNA in human primary tumors might lead to interference of TGFbeta signaling or
      some class of WNT signaling. This is the first report on molecular cloning of
      GIPC2, the second member of the GIPC gene family, which is down-regulated in
      human primary kidney and colorectal tumors.

PMID- 11836571
TI  - Molecular cloning and characterization of human GIPC3, a novel gene homologous to
      human GIPC1 and GIPC2.
AB  - Kermit is a Xenopus orthologue of human GIPC1/GIPC, which interacts with Frizzled
      3 (FZD3) class of WNT receptor to modulate WNT signaling. GIPC1 interacts with
      TGFbeta type III receptor to enhance TGFbeta signaling. We have recently cloned
      and characterized a novel GIPC1-related gene, GIPC2. During isolation of GIPC2,
      we identified another novel GIPC1-related gene, GIPC3, by using bioinformatics.
      In this study, we isolated GIPC3 cDNAs from poly(A)+ RNA of human fetal lung.
      GIPC3 encoded a 312-amino-acid protein with a central PDZ domain, which showed
      59.9% total-amino-acid identity with GIPC1, 55.3% total-amino-acid identity with
      GIPC2, and 57.2% total-amino-acid identity with Xenopus Kermit. GIPC3 gene on
      human chromosome 19p13.3 was found to consist of 6 exons, just like GIPC1 gene
      and GIPC2 gene. The 4.5-kb GIPC3 mRNA was almost ubiquitously expressed in normal
      adult tissues as well as in normal fetal tissues. Expression level of GIPC3 mRNA
      was relatively higher in jejunum, followed by lymph node, parietal lobe in brain,
      fetal spleen, and fetal thymus. GIPC3 mRNA was expressed in cervical cancer cell
      line HeLa S3, chronic myelogenous leukemia cell line K-562, and melanoma cell
      line G-361. GIPC3 mRNA was also expressed in gastric cancer cell lines TMK1 and
      MKN7; however, expression level of GIPC3 mRNA in TMK1 and MKN7 cells were
      significantly lower than that in normal stomach. This is the first report on
      molecular cloning of GIPC3, the third member of the GIPC gene family.

PMID- 11836572
TI  - Mechanism of action of herbal supplement PC-SPES: elucidation of effects of
      individual herbs of PC-SPES on proliferation and prostate specific gene
      expression in androgen-dependent LNCaP cells.
AB  - PC-SPES is a herbal mixture used by prostate cancer patients as an alternative
      form of treatment. Since PC-SPES is derived from eight individual herbs, each
      with distinct as well as overlapping properties, it is of interest to investigate
      whether a particular herb in the formulation principally accounts for the
      biological properties of PC-SPES. We tested the ability of extracts from
      individual herbs, using amounts estimated to be equivalent to that present in the
      herbal mixture, to suppress LNCaP cell growth and/or lower PSA expression, in
      comparison with cells treated with PC-SPES. Cells were incubated with 0, 1, and 5
      microl/ml of single herbal extract for 72 h and proliferation/viability was
      measured by trypan blue exclusion. LNCaP cells treated with 5 microl/ml ethanol
      extracts of PC-SPES showed a 72-80% reduction in cell growth, and had a similar
      decrease in cell viability. These results contrasted with cells incubated with 5
      microl/ml of individual herbal extract, which suppressed growth in the following
      order: Dendranthema morifolium Tzvel (85.2% reduction) > Panax pseudo-ginseng
      (80.9%) > Glycyrrhiza uralensis Fisch (73%) > Rabdosia rubescens Hara (70.8%) >
      Scutellaria baicalensis Georgi (66.5%) > Ganoderma lucidum Karst (63.5%) > Isatis
      indigotica Fort (50.0%) > Serenoa repens (14.5%). Analysis of efficacy of
      individual herbs to control intracellular/secreted PSA levels and the expression
      of AR and PSA revealed that only Glycyrrhiza uralensis Fisch, Scutellaria
      baicalensis Georgi and Serenoa repens lowered intracellular and secreted PSA,
      while the remaining herbs actually increased PSA expression. Also, no uniform
      response in AR/PSA was observed in individual herb treated cells, contrary to PC
      SPES, which elicited a coordinated change in AR/PSA. Lack of concordance between
      changes in prostate cell growth and prostate specific gene expression makes it
      unlikely that the activity of a single herb can account for the overall effects
      of PC-SPES.

PMID- 11836573
TI  - Low sex steroid environment affects survival and steroid secretion of ovarian
      tumour cells in primary cultures.
AB  - Ovarian epithelial tumours are considered to be endocrine related. The effects of
      an environment with low levels of the steroid hormones 17 beta-estradiol,
      testosterone or progesterone on cell survival and steroid secretion were studied
      in primary cell cultures derived from 25 patients suffering from epithelial
      ovarian tumours. Tumour cells cultured in 17 beta-estradiol and testosterone
      showed a reduced cell survival (-10.3 +/- 2.3% and -15.6 +/- 2.7% minimum
      survival respectively). This reduction was inversely proportional to hormone
      concentrations within the range studied. No similar effect was observed in the
      progesterone cultures. It was found that 17 beta-estradiol was secreted from the
      primary cell cultures and, interestingly, the amount of 17 beta-estradiol
      secreted increased with increasing levels of 17 beta-estradiol in the
      environment. Neither progesterone nor testosterone production was observed in any
      of the cultures studied. It is believed that 17 beta-estradiol has an
      antiapoptotic effect on ovarian surface epithelial (OSE) cells. Reduction of 17
      beta-estradiol in the environment may inhibit this effect, resulting in reduced
      cell survival. The ability of ovarian epithelial tumour cells to secrete 17 beta
      estradiol suggests that epithelial ovarian tumours play an active role in
      altering their own hormonal environment, promoting tumour progression.

PMID- 11836574
TI  - Genetic aberration on chromosome 10 in human oral squamous cell carcinoma.
AB  - Recently a tumor suppressor gene, a deleted in malignant brain tumor gene
      (DMBT1), was detected on chromosome 10. In some types of tumors, the frequent
      deletion of DMBT1 locus have been reported as well as loss of heterozygosity
      (LOH) on chromosome 10. However, little is known relating to human oral squamous
      cell carcinoma (OSCC). To study the genetic aberrations on chromosome 10 in OSCC,
      we performed polymerase chain reaction (PCR) analysis of microsatellite
      polymorphisms corresponding to 16 loci, containing 2 DMBT1 loci. We examined 38
      oral primary squamous cell carcinoma (SCC) tissues and corresponding normal
      tissues. Microsatellite instability (MI) was detected at least on 1 of the 16
      loci in 15 (39.5%) of 38 cases, and loss of heterozygosity (LOH) at least 1 of
      the 16 loci was also observed in 28 (73.7%) of 38 cases. LOH was accumulated at
      D10S202 (34.6%) and D10S217 (28.6%), suggesting the presence of two putative
      tumor suppressor genes associated with OSCC. The 2 DMBT1 loci, D10S209 and
      D10S587, had comparatively high frequent LOH (20.0 and 22.7%, respectively),
      maybe indicating the important role of DMBT1 in OSCC. No significant correlation
      between histological differentiation and LOH was found. These results suggest
      that genetic aberrations on chromosome 10 play important roles in the oncogenesis
      of OSCC.

PMID- 11836575
TI  - Expression of peroxisome proliferator-activated receptor gamma and the growth
      inhibitory effect of its synthetic ligands in human salivary gland cancer cell
      lines.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) is a member of the
      nuclear receptor superfamily of ligand-activated transcription factors. It is
      expressed in several tissue types, including adipose tissue in which it
      stimulates adipogenesis. Recent studies have demonstrated that PPARgamma ligands
      induce cellular differentiation and inhibit cell growth in carcinomas of various
      organs including the breast, prostate, lung, colon, stomach, bladder, and
      pancreas. However, whether PPARgamma is expressed in human salivary gland tumors
      and its function in this tissue is unknown. In the present study, we examined
      PPARgamma gene expression in human salivary gland cancer cells and tested its
      ligands for any antitumor effect. PPARgamma mRNA was detected by RT-PCR in both
      benign and malignant salivary gland tumor tissues. The effect of PPARgamma on
      cell growth was investigated using four human salivary gland cancer cell lines;
      HSG, AZA3, HSY and TYS, which were confirmed to express PPARgamma1 mRNA and
      protein. Retinoid X receptor alpha protein, which forms heterodimers with
      PPARgamma, was also detected in all the cells tested. Data obtained by luciferase
      assay indicated that the intrinsic PPARgamma protein was activated by the
      synthetic ligands, troglitazone and pioglitazone, but not by the natural ligand,
      15-deoxy-delta12, 14-prostaglandin J2. The synthetic PPARgamma ligands,
      particularly troglitazone, caused significant dose-dependent inhibition of cancer
      cell growth. Furthermore, the overexpression of PPARgamma1 or PPARgamma2 in
      cancer cells also reduced significantly their growth rate. These results suggest
      that PPARgamma and its synthetic ligands suppress the growth of human salivary
      gland cancer cells and it may be a useful molecular target for cancer treatment.

PMID- 11836576
TI  - Identification of a minimal c-erbB-2 promoter region that mediates preferential
      expression of a linked foreign gene in human breast cancer cells.
AB  - The c-erbB-2 oncogene is frequently overexpressed in human breast cancer partly
      due to its elevated transcription level. The promoter regions of the c-erbB-2
      gene could therefore activate the transcription of a linked foreign gene
      preferentially in breast cancer cells. Previous reports showed that the 533-bp (
      495/+38, +1 corresponds to the transcription start site) or the 251-bp (-213/+38)
      genomic fragment included the cis-acting elements which stimulated the
      transcription of a fused gene in breast cancer cells. Our previous study also
      indicated that the 251-bp fragment could transcribe the reporter gene better than
      the 533-bp fragment and that the 124-bp (-86/+38) region did not support the
      transcription of a linked reporter gene. In this study, we precisely analyzed the
      promoter activity of the genomic region between -213/+38 and -86/+38 in breast
      cancer, non-breast cancer cells and fibroblasts, and found that deletion of 22-bp
      from the 251-bp fragment markedly decreased the transcriptional activation in
      breast cancer cells. Although the 22-bp deletion also decreased the promoter
      activity in non-breast cancer cells, the deletion did not influence the activity
      in fibroblasts. Since the promoter activity of shorter genomic fragments beyond
      the 22-bp deletion remained low in breast cancer cells, the -213/-191 region
      contains a cis-acting element(s) that is minimally required for the preferential
      expression in breast cancer cells.

PMID- 11836577
TI  - AIDS-related non-Hodgkin's lymphoma: clinico-pathological characteristics and
      therapeutic strategies (review).
AB  - High-grade B-cell non-Hodgkin's lymphoma (NHL), a diagnostic disease for the
      acquired immunodeficiency syndrome (AIDS), is a late manifestation of HIV
      infection and is generally related to severe lymphopenia. We reviewed the main
      clinico-pathological features of this disease and analysed its pathogenetic
      mechanisms with potential therapeutic implications.

PMID- 11836578
TI  - Participation of Fas-mediated apoptotic pathway in KB, a human head and neck
      squamous cell carcinoma cell line, after irradiation.
AB  - In head and neck clinical oncology, recurrent cancer after initial irradiation
      therapy is no longer sensitive to irradiation. To explore the irradiation
      resistance in head and neck squamous cell carcinoma, a human cell line, KB,
      derived from the floor of the oral cavity was used. The participation of the Fas
      mediated apoptotic pathway was suggested by the upregulation of the surface Fas
      molecule, the reduction of the apoptotic cell fraction after inhibition of
      caspase 8 which is a Fas-related initiator caspase, and the changes in Fas
      related genes after irradiation. Therefore, it is suggested that disruption of
      the Fas-mediated apoptotic pathway participates in the acquisition of irradiation
      resistance in HNSCC.

PMID- 11836579
TI  - Thin section arrays for I-FISH analysis of chromosome-specific imbalances in
      squamous cell carcinomas of the head and neck.
AB  - Thin section arrays of 20 head and neck squamous cell carcinomas were studied by
      I-FISH for gains (including amplification) and losses of specific genomic
      segments. These arrays allow the examination not only of a number of tumor
      sections but also of the surrounding margins and of inconspicuous control tissue
      in one experiment. All tumor sections examined significantly differed from the
      inconspicuous control tissues by containing more or less extensive cell
      populations with aberrant signal constitutions. In no case, however, did the
      aberrant population constitute the whole area of the section. Gains of signals
      were strikingly more frequent than were losses. All tumors showed significant
      gains of the segments examined, the highest differences between tumor and control
      sections were found for the segments 9q34 and 8q24, followed by 5p15.3 and 11q13.
      Amplifications were most frequently found of 11q13: 8 of the 20 tumors showed
      amplifications in more than 20% of the nuclei, while no nucleus with more than
      four signals was found in any of the control tissues (control: 0%).
      Amplifications of the target sequences on chromosomes 8 (14 tumors) and 9 (8
      tumors) were observed in low but significant percentages of nuclei, no
      significant cell population was detected with an amplification of 5p15.3.
      Fourteen tumors exhibited a significant loss of 13q14, and only 8 tumors a
      significant loss at any other site. In the tumor margin sections, in most cases,
      the margins apparently were also affected by the one or the other of the genomic
      changes of the pertinent primary tumor. Nevertheless, there were, in some cases,
      also large differences depending on the way of analysis, but also on the specific
      signal constitution considered. Tumor stages T3 and T4 tended to have higher
      frequency of nuclei with gains of 5p15.3, 8q24, and 11q13 as compared to T2
      tumors and less gains of 9q34 and loss of 13q14. With the exception of 8q24 and
      13q14 alterations there was also a trend to higher percentages of aberrant nuclei
      in the margin of T3-4 tumors vs. T2 tumors.

PMID- 11836580
TI  - Sulforaphane and its metabolite mediate growth arrest and apoptosis in human
      prostate cancer cells.
AB  - The relation between the consumption of cruciferous vegetables and reduced
      prostate cancer occurrence has been documented, although the responsible
      phytochemicals are unknown. The effects of sulforaphane (SFN) which occurs as the
      precursor glucosinolate in broccoli and other cruciferous vegetables, and its
      metabolite N-acetylcysteine conjugate (SFN-NAC) on prostate cancer cells were
      investigated. SFN and SFN-NAC were analyzed with the androgen-dependent human
      prostate cancer LNCaP cell line model. Cell growth and apoptosis were determined
      with the expression of androgen receptor and prostate specific antigen, DNA
      synthesis, cell cycle progression, DNA strand breaks and caspase activation to
      ascertain the effects and mechanism. SFN and SFN-NAC were demonstrated for the
      first time to mediate a dose-dependent apoptosis and growth arrest in the
      prostate cancer cells. Caspases were activated and DNA strand breaks were
      detected in apoptotic cells. The expression of phosphorylated and
      dephosphorylated androgen receptors, and the production of prostate specific
      antigen were attenuated. The expression of cyclin D1 and DNA synthesis were
      inhibited along with G1 cell cycle block, causing decreased cell density and
      growth. SFN and its metabolite SFN-NAC have similar activities to induce growth
      arrest and apoptosis, indicating that the effects of SFN are maintained through
      the metabolic processes. SFN as a dietary component of cruciferous vegetables
      active in the prevention of prostate cancer is discussed.

PMID- 11836581
TI  - Telomere dynamics, aneuploidy, stem cells, and cancer (review).
AB  - The real cause of genetic instability, which is the hall-mark of most cancers, is
      poorly understood. Specific gene mutations and acquired aneuploidy have been
      implicated as the root causes of genetic instability. Here we propose and cite
      evidence for the hypothesis that genetic instability of cancer cells is caused by
      telomere dynamics, erosion and/or amplification of the TTAGGG repeat sequences
      present at chromosomal termini. Since telomeres determine the domain of
      individual chromosomes within a nucleus and protect them from internal and
      external challenges, their erosion will destabilize the cell karyotype. Our
      hypothesis predicts that telomere dynamics provides the single unifying mechanism
      playing a major role in speciation, aging and cancer development. It was found
      that metastatic cancers of different histologic phenotypes, as well as mammalian
      taxa with active speciation and larger numbers of species exhibit amplification
      of their telomeric DNA as compared to non-metastatic counterpart cancers and taxa
      with only a limited number of species. The dynamic nature of this DNA can be
      found not only in the cancer cells but also in the peripheral lymphocytes of
      cancer patients. Human syndromes such as Down, Turner, Bloom, Werner, Fanconi,
      ataxia and many others, show aneuploidy and also are prone to develop various
      malignancies and premature aging. We have found that <normal cells> of all these
      syndromes have a reduced amount of telomeric DNA associated with specific mitotic
      catastrophes as compared to cells of age- and sex-matched normal individuals.
      From these and additional data generated by our group concerning speciation,
      aging and cancer karyotypes, we conclude that aneuploidy, which is responsible
      for birth defects, cancer initiation and is a major player in natural speciation,
      is a consequence of telomere dynamics. Because telomere reduction is linked to
      the aging process, which is a risk factor for cancer development in the human
      population, our hypothesis offers a unifying mechanism for the initiation of both
      hematologic and solid cancers, as well as for the origin of new species.

PMID- 11836582
TI  - Tumour-inhibitory and antimetastatic effects of IL-2 in mice carrying MHC class I
      tumours of HPV16 origin.
AB  - Oncogenic, moderately immunogenic, MHC class I- and class II-, B7-, MK16/1/III
      ABC (MK16) cells were previously established by co-transfection of HPV16 E6/E7
      and activated H-ras oncogene DNA into C57BL/6 kidney cells. Subcutaneous
      transplantation of these cells produced progressively growing local neoplasms
      which metastasized spontaneously to lungs and lymph nodes. The MK16 cells were
      implanted into syngeneic mice and used to examine whether the tumour lacking the
      signal molecules required for the induction of and sensitivity to T cell immunity
      is susceptible to local IL-2 treatment and IL-2 gene therapy. Peritumoural
      administration of human rIL-2 or murine IL-2 gene-modified MK16 tumour vaccine
      inhibited growth of subcutaneous MK16 tumour transplants and reduced the number
      of their lung metastases. Spleen cells from MK16 tumour-immunized mice were not
      cytolytic when allowed to react with the MK16 target cells, although they
      efficiently lysed the MHC class I+ malignant TC1 cells, obtained from C57BL/6
      lung cell cultures after transfection with the same plasmids as those used for
      the derivation of the MK16 cells. However, when the MK16 cells were cultivated in
      vitro in the presence of IFNgamma, they acquired, together with the expression of
      MHC class I molecules, the sensitivity to the cytolytic effect of spleen cells
      from the MK16 tumour-immunized mice. These results indicate that experimental
      tumours which are MHC class I- and mimick in this respect a high proportion of
      human HPV16-associated carcinomas are suitable for IL-2 treatment.

PMID- 11836583
TI  - Molecular genetic evaluation of fluorescence diagnosis in bladder cancer.
AB  - Fluorescence diagnosis of superficial bladder cancer using 5-aminolevulinic acid
      (ALA) is a highly sensitive technique (95%). However, the specificity is only 60
      70% due to false-positive results after histopathological examination. We
      hypothesized that the biopsies in fluorescence endoscopy could represent early
      preneoplastic lesions not detectable by histopathology. In order to evaluate the
      specificity of fluorescence endoscopy at the molecular genetic level we performed
      comparative genomic hybridization (CGH) and investigated telomerase activity of
      ALA-positive tissue samples. For CGH, DNA was isolated from 5-10 frozen sections.
      Tumor and normal (control) DNAs were amplified by DOP-PCR and labeled with biotin
      dUTP and digoxigenin-dUTP, respectively. Hybridization and detection were carried
      out according to standard protocols. Telomerase activity was analyzed using a non
      radioactive system (TRAP-assay). In 33 out of 118 bladder cancer cases (28%)
      detected by conventional cystoscopy, additional suspicious areas were found using
      ALA. CGH revealed genetic changes in 27% of samples with non-malignant
      histological diagnoses. Telomerase activity was found in 59% of these samples.
      Tumor samples showed genetic alterations in 84% and in 69% telomerase activity
      occurred. The type of genetic alterations in the normal biopsies was identical to
      the tumors. Based on these molecular data, the portion of false-positive results
      obtained by fluorescence diagnosis is lower than defined by histopathology alone.
      Genetic alterations and activation of telomerase activity are early events of
      tumor development in bladder cancer occurring earlier than histological features
      of neoplasia. The clinical importance of fluorescence diagnosis and the possible
      reduction of the recurrence rate have to be shown in ongoing clinical studies.

PMID- 11836584
TI  - Expression of p53 in preneoplastic and early neoplastic bronchial lesions.
AB  - p53 alteration has been reported to be an early event in bronchial
      carcinogenesis. Our study purpose was to determine the rate of p53 expression in
      the various preneoplastic and early neoplastic bronchial lesions obtained by
      biopsy during fluorescence bronchoscopy and to analyse its association with
      patients characteristics. Various stages of preneoplastic lesions as well as
      radio-occult lung cancer were studied in biopsies obtained by fluorescence
      bronchoscopy. We assessed the expression of p53 by immunohistochemistry using
      monoclonal antibody clone DO7. The p53 expression was considered as positive if >
      or = 1% of cells were positive and the level of positivity was expressed in
      percentage of positive cells. Fourteen patients were included in each category of
      preneoplastic lesions. At the threshold of 1% of positive cells p53 expression
      was observed in 28.5% of the patients with a histologically normal epithelium.
      This number of positive patients increased with the severity of preneoplastic
      lesions and reached 100% in the mild dysplasia. The mean rates of p53 positive
      cells for normal epithelium, hyperplasia, metaplasia, mild and severe dysplasia,
      carcinoma in situ and invasive radio-occult carcinoma were respectively 0.9, 3.4,
      9.1, 20.5, 50.2, 34.7 and 42.5%. There was no statistically significant
      correlation between p53 expression and patient characteristics such as sex, age,
      smoking habits and indication for fluorescence bronchoscopy. The alteration of
      p53 expression in patients with high risk of lung cancer was an early event: this
      abnormality increased with the severity of the lesions, without significant
      correlation with patient characteristics.

PMID- 11836585
TI  - Primary colorectal tumour is not an accurate predictor of thymidylate synthase in
      lymph node metastasis.
AB  - Analysis of tumour markers is helping to predict individual patient response to
      chemotherapy. However, the difficulties in obtaining metastatic disease samples
      has led to a reliance on assessment of primary tumour, with little data on its
      predictive ability. This study assessed thymidylate synthase (TS), a target for
      the commonly used drug 5FU, in 42 paired primary colorectal tumour and lymph node
      metastasis. High TS staining was seen in 63% of primary colon tumour cells and
      81% of the secondary lymph node. Primary tumour did not have significant
      predictive power for secondary tumour samples (kappa=0.125; p=0.38). There was no
      significant relationship between TS staining and expression of G1/S cell cycle
      proteins p21, p27, p53, cyclin D1, proliferating cell nuclear antigen (PCNA) and
      retinoblastoma protein (Rb) (p>0.05 in all cases). Discordance in TS protein
      levels between primary and secondary tumours demonstrates the danger of
      predicting outcome after chemotherapy in metastatic colorectal cancer from the
      primary tumour.

PMID- 11836586
TI  - The -9Ala/-9Val polymorphism in the mitochondrial targeting sequence of the
      manganese superoxide dismutase gene (MnSOD) is associated with age among
      Hispanics with colorectal carcinoma.
AB  - Recently a T to C substitution in the mitochondrial targeting sequence of the
      manganese superoxide dismutase (MnSOD) gene was observed that changes the amino
      acid sequence of the protein from valine (V) to alanine (A) and is associated
      with a decreased defense capacity against oxidative stress. We investigated
      whether this polymorphism of the MnSOD gene is associated with increased risk for
      colorectal cancer among Hispanics and non-Hispanic whites. All controls (63
      Hispanic, 58 non-Hispanic) and colorectal cancer cases (64 Hispanic, 61 non
      Hispanic) were genotyped using a fluorogenic 5'-nuclease assay. The observed
      alanine frequency was 0.62 among disease-free Hispanics and 0.51 among non
      Hispanic whites controls. No significant differences were observed between cancer
      patients and disease-free controls in either ethnic group (p=0.90) excluding this
      polymorphism as a risk factor for colorectal cancer in Hispanics and non-Hispanic
      whites. Among Hispanic individuals with colorectal cancer the alanine allele was
      observed more frequently in young patients. Patients homozygous for the alanine
      allele (24/64) showed a mean age of 37.6 years compared to 42.3 years for
      heterozygotes (29/64) and 48.4 years for patients homozygous for the V allele
      (p=0.045, ANOVA). The data demonstrate that the -9Val/-9Ala substitution is more
      common in Hispanics than in non-Hispanic whites. Furthermore, the data suggest
      that the alanine allele of this polymorphism may be associated with an increased
      risk to develop colorectal cancer at a young age in Hispanics.

PMID- 11836587
TI  - Neovascularization in pancreatic ductal adenocarcinoma: Microvessel count
      analysis, comparison with non-cancerous regions and other types of carcinomas.
AB  - Although neovascularization is regarded as an essential factor for tumor growth,
      it is unclear whether pancreatic adenocarcinoma is also influenced by this
      process. Furthermore, the reported microvessel count (MVC) data can not be
      compared due to the diversity of evaluating methods, and the relation between MVC
      data and metastatic potentials remains controversial. A total of 24 pancreatic
      adenocarcinomas and 24 adjacent non-cancerous pancreatic parenchyma were analyzed
      for MVC using anti-CD31 antibody. In addition, the MVC of 15 hypervascular tumors
      (10 hepatocellular carcinomas: HCC and 5 islet cell pancreatic tumors: ICT), 30
      other types of adenocarcinomas (10 gastric, 10 colon and 10 intraductal papillary
      mucinous tumors of the pancreas: IPMT), as well as that of non-cancerous areas,
      were also analyzed. The extent of hepatic and peritoneal spread in 24 pancreatic
      adenocarcinoma patients was classified and correlations with MVC were evaluated.
      The mean MVC of 24 pancreatic adenocarcinomas (31.6 +/- 11.1) was actually lower
      than that of HCCs (91.6) or ICTs (56.4). The diversity is temperate as compared
      with that of other adenocarcinomas, i.e., 42.9 in gastric carcinomas, 35.6 in
      colon carcinomas and 32.5 in IPMT. MVC in non-cancerous areas were significantly
      higher in the pancreas (112.8) than in the stomach (29.6) or colon (26.3). MVC
      ratios of the cancerous area to the non-cancerous area were significantly lower
      in the pancreas (0.2818 +/- 0.100) than in the stomach (1.569 +/- 0.526, p<0.001)
      or the colon (1.423 +/- 0.493, p<0.001). MVC were higher in diffuse hepatic
      metastasis patients (36.0) than in limited metastasis patients (25.7). In
      conclusion, MVC in pancreatic adenocarcinoma revealed vascular volume to actually
      be lower than that of hypervascular tumors. We believe, however, that this
      hypovascularity is due mainly to contrast with the hyper-vascular non-cancerous
      pancreas, since MVC in the cancerous area itself was at the same level as in
      other adenocarcinomas. In addition, we revealed MVC to be of value for predicting
      the extent of liver metastasis.

PMID- 11836588
TI  - Expression of Fas ligand in patients with evident skull base involvement of
      nasopharyngeal carcinoma.
AB  - We investigated whether skull base involvement in patients with nasopharyngeal
      carcinoma (NPC) is correlated with expression of Fas ligand (FasL) in NPC cells.
      A prospective assessment of FasL expression was determined by
      immunohistochemistry and in situ hybridization in 98 patients with newly
      diagnosed NPC. Among these patients, 21 had evident skull base involvement.
      Expressions of human apoptosis-related genes and FasL were confirmed by reverse
      transcription-polymerase chain reaction. Relation between the frequency of skull
      base involvement and FasL expression was analyzed by Chi-square and multivariate
      analyses. FasL expression was detected in 32 (32.6%) of 98 pathological sections.
      Compared to patients with low FasL expression in tumors, patients with notable
      FasL expression had higher incidence of skull base involvement (28.6 vs. 71.4%,
      p<0.005). Expression of FasL in tumor cells was correlated with the higher
      frequency of skull base involvement in patients with NPC.

PMID- 11836589
TI  - Clinical significance of p53, MDM2 and bcl-2 expression in transitional cell
      carcinoma of the bladder.
AB  - We investigated the prognostic and predictive relevance of p53, MDM2, and bcl-2
      protein expression in patients with transitional cell carcinoma (TCC) of the
      bladder. The expression of p53, MDM2 and bcl-2 protein was studied by
      immunohistochemical methods in paraffin-embedded specimens from 119 patients
      whose clinicopathologic data confirmed TCC of the bladder. Multivariate analyses
      of prognostic factors were performed, and correlations with classical
      clinicopathologic parameters were examined. Sixty-one, 12, and 17% of cases were
      considered positive for expression of p53, MDM2 and bcl-2, respectively. p53
      expression correlated with stage (p=0.0209), but not MDM2 and bcl-2 with any
      clinicopathologic parameters. In Cox's regression analysis, staging demonstrated
      a statistically worse prognosis (hazard ratio 1.636; p=0.0059) while bcl-2
      (hazard ratio 0.179; p=0.0474) expression showed favorable prognosis in stage T2
      4 invasive TCC of the bladder. Co-expression with p53/MDM2 (hazard ratio 0.367;
      p=0.0401) and p53/bcl-2 (hazard ratio 3.487; p=0.0111) overexpression were
      associated with favorable and unfavorable prognosis in stage T2-4 invasive TCC of
      the bladder, respectively. Our results indicate that staging is the most useful
      parameter to predict clinical outcome in patients with TCC of the bladder.
      Determinations of bcl-2 and co-expression p53/MDM2 and p53/bcl-2 may be useful
      for predicting tumor behavior and prognosis in stage T2-4 invasive type TCC of
      the bladder.

PMID- 11836590
TI  - Differential expression of heat shock protein 27 in normal oral mucosa, oral
      epithelial dysplasia and squamous cell carcinoma.
AB  - The aim of this study was to evaluate HSP27 expression in fetal, normal and
      inflamed oral mucosal epithelium and in oral premalignant epithelial lesions and
      in their ensuing invasive cancers. In developing human oral epithelia,
      immunoreactions for HSP27 were moderately observed in suprabasal keratinocytes of
      palate and tongue. Normal oral epithelium had an intense suprabasal positivity.
      In inflamed oral mucosa, HSP27 staining was stronger in basal and suprabasal
      keratinocytes than in normal epithelium. Most oral premalignant lesions showed no
      (5 cases, 29%) or low (8 cases, 46.4%) staining. In OSCC both low and high HSP27
      levels of expression were observed. HSP27 immunolabelling was down-regulated in
      poorly differentiated areas and up-regulated in highly differentiated ones. These
      findings indicated that HSP27 expression seems to protect cells from apoptosis
      during inflammation, while the down-regulation in dysplasia could impair the
      protective mechanism against mutagenesis induced by environmental factors and
      thus enhancing the transformation of oral epithelial dysplasia into OSCCs.

PMID- 11836591
TI  - Cancer vaccines: an update with special focus on ganglioside antigens.
AB  - Vaccine development is one of the most promising and exciting fields in cancer
      research; numerous approaches are being studied to developed effective cancer
      vaccines. The aim of this form of therapy is to teach the patient's immune system
      to recognize the antigens expressed in tumor cells, but not in normal tissue, to
      be able to destroy these abnormal cells leaving the normal cells intact. In other
      words, is an attempt to teach the immune system to recognize antigens that
      escaped the immunologic surveillance and are by it, therefore able to survive
      and, in time, disseminate. However each research group developing a cancer
      vaccine, uses a different technology, targeting different antigens, combining
      different carriers and adjuvants, and using different immunization schedules.
      Most of the vaccines are still experimental and not approved by the US or
      European Regulatory Agencies. In this work, we will offer an update in the
      knowledge in cancer immunology and all the anticancer vaccine approaches, with
      special emphasis in ganglioside based vaccines. It has been demonstrated that
      quantitative and qualitative changes occur in ganglioside expression during the
      oncogenic transformation. Malignant transformation appears to activate enzymes
      associated with ganglioside glycosylation, resulting in altered patterns of
      ganglioside expression in tumors. Direct evidence of the importance of
      gangliosides as potential targets for active immunotherapy has been suggested by
      the observation that human monoclonal antibodies against these glycolipids induce
      shrinkage of human cutaneous melanoma metastasis. Thus, the cellular over
      expression and shedding of gangliosides into the interstitial space may play a
      central role in cell growth regulation, immune tolerance and tumor-angiogenesis,
      therefore representing a new target for anticancer therapy. Since 1993
      researchers at the University of Buenos Aires and the University of Quilmes
      (Argentina), have taken part in a project carried out by the <Centro de
      Inmunologia Molecular> (CIM) from La Havana, Cuba, to developed new strategies
      for specific active immunotherapy. The project included two ganglioside based
      vaccines and one anti-idiotypic vaccine. We focused on two antigens: first GM3,
      an ubiquitous antigen which is over-expressed in several epithelial tumor types;
      and a second one, N-Glycolyl-GM3 a more <tumor specific> molecule, not being
      expressed in normal tissues and recently found in several neoplastic cells, in
      particular breast, melanoma and neuroectodermal cancer cells. We developed two
      vaccines, one with each antigen, both using proteins derived from the outer
      membrane proteins (OMP) of Neisseria Meningitidis B, as carriers. We developed
      also the 1E10 vaccine; an anti-idiotype vaccine designed to mimic the N-Glycolyl
      GM3 gangliosides. This monoclonal antibody is an Ab2-type-antibody which
      recognizes the Ab1 antibody called P3, the latter is a monoclonal antibody that
      specifically recognizes gangliosides as antigens. Since 1998 we initiated a
      clinical development program for these three compounds. Results of the phase I
      clinical trials proved that the three vaccines were safe and able to elicit
      specific antibody responses. In addition we were able to demonstrate the
      activation of the cellular arm of the immune response in patients treated with
      the GM3 vaccine. Although phase I trials are not designed to evaluate antitumor
      efficacy, it was encouraging to observe tumor shrinkage in some patients treated
      both with the GM3 and N-Glycolyl-GM3 vaccines. We have already begun a phase II
      program in several neoplastic diseases, with all three vaccines.

PMID- 11836592
TI  - Clinical evaluation of granisetron as an inhibitor of nausea and vomiting induced
      by oral anticancer drugs.
AB  - In order to inhibit the nausea and vomiting induced by oral anticancer drugs,
      granisetron was administered orally at a dose of 2 mg once a day, and its
      usefulness and safety were evaluated. The subjects were 26 outpatients with
      gastric or colon cancer receiving chemotherapy with oral anticancer drugs and
      complaining of gastrointestinal symptoms. A record sheet was handed to the
      patients. In comparison with the condition before treatment, the patients were
      instructed to indicate on the record sheet the severity of nausea (4 grades),
      presence or absence of vomiting, and degree of appetite (4 grades) after
      treatment, and thereby to evaluate the clinical efficacy or antiemetic effect
      every day in accordance with clinical efficacy evaluation criteria of 4 grades
      (very effective, effective, slightly effective, and ineffective). i) Nausea
      disappeared in 47.8% of the patients on the 1st day of treatment and in 65.2% on
      the 5th day of treatment. ii) Vomiting was observed in 2 and 3 patients on the
      1st and 3rd day, respectively, but not on the 4th day of treatment or thereafter.
      iii) The efficacy rate, comprising both very effective and effective, was 69.5%
      on the 1st day of treatment, and increased gradually to reach 78.2% on the 5th
      day of treatment. iv) There was no adverse reaction or abnormality of laboratory
      test values attributable to granisetron. Granisetron was safe and effective
      against nausea and vomiting induced by oral anticancer drugs.

PMID- 11836593
TI  - Treatment of patients with superficial bladder cancer by intravesical
      instillation of anticancer drugs plus oral chemotherapy following TUR-Bt: a
      randomized controlled trial.
AB  - We conducted a randomized controlled trial to compare local recurrence rate after
      transurethral resection of superficial bladder cancer treated by either
      intravesical instillation of an anticancer drug alone (method A) and the
      intravesical instillation plus oral chemotherapy (doxifluridine, 5'-DFUR, an
      intermediate metabolite of capecitabine) (method B). Results between groups
      showed no difference in recurrence-free survival curves in 196 patients subjected
      to primary analysis. However, patients subjected to secondary analysis (method B,
      over 3 months administration of 5'-DFUR) showed a significantly better prognosis
      than method A (p=0.0244, Wilcoxon). Regarding correlation between thymidine
      phosphorylase (TP, an enzyme to convert 5'-DFUR to 5-fluorouracil) level and
      prognosis, method A patients showed poorer prognosis in higher TP level cases
      than in lower TP levels. However, there was no significant difference in
      prognosis between those with higher and lower TP levels. In method B patients,
      there was no difference in prognosis between those with higher and lower TP
      levels. Method A patients tended to show a slightly better prognosis than those
      with lower TP levels, while method B patients tended to have a slightly better
      prognosis with higher TP levels, but no significant difference was observed.
      These findings suggested 5'-DFUR showed a mild efficacy in patients with higher
      TP levels and that patients with higher TP levels resulted in poorer prognosis.

PMID- 11836594
TI  - Prognostic significance of a combination of thymidylate synthase and
      dihydropyrimidine dehydrogenase activities in grades 1 and 2 superficial bladder
      cancer.
AB  - There is no potent prognostic marker for recurrence in superficial bladder cancer
      at present. Thymidylate synthase (TS) is a key enzyme for pyrimidine synthesis.
      Dihydropyrimidine dehydrogenase (DPD) is an important pyrimidine salvage enzyme.
      We evaluated a combination of TS and DPD activities as a prognostic marker for
      recurrence in grade 1 and 2 superficial bladder cancer. The levels of TS and DPD
      activities in non-fixed fresh frozen bladder cancer specimens were determined
      biochemically by the 5-fluoro-2'-deoxyuridine 5'-monophosphate binding assay and
      the 5-fluorouracil degradation assay, respectively. Significantly, patients with
      low TS activity and high DPD activity had a longer post-operative tumor-free
      interval than those with either high TS activity or low DPD activity in the 2
      year follow-up. There were no statistical differences observed in patient's sex
      and age as well as the histologic stage and grade of bladder cancer between the
      two groups. In addition, there is no correlation between TS and DPD activities.
      The present study suggests that a combination of TS and DPD activities may be an
      independent prognostic indicator for recurrence in grade 1 and 2 superficial
      bladder cancer, and that either high TS activity or low DPD activity predicts
      early recurrence.

PMID- 11836595
TI  - Overexpression of p53 protein and point mutation of K-ras genes in primary
      carcinoma of the small intestine.
AB  - Primary carcinoma of the small intestine is rare and represent about 0.5% of all
      gastrointestinal malignancies. The aim of this study was to examine the
      biological characteristics of primary carcinoma of the small intestine by
      immunohistochemical and nested polymerase chain reaction methods. Thirty-five
      primary carcinomas (12 in the duodenum and 23 in the jejunum or ileum) from 35
      patients were studied clinicopathologically and examined for overexpression of
      p53 protein. In 22 of these 35 cases, point mutation at codon 12 of the K-ras
      gene was detected by the nested polymerase chain reaction and restriction
      fragment length polymorphism method. All the duodenal carcinomas were well
      differentiated type and the rate of these carcinomas was significantly higher
      than that of jejunal or ileal carcinomas (100% vs. 65%). Fourteen cases showed
      overexpression of p53 (40%), and p53 tended to be expressed more frequently in
      poorly-differentiated type (71%) compared to well-differentiated type (30%). Only
      2 out of 22 carcinoma cases showed K-ras gene mutation, and both were duodenal
      carcinomas. These findings suggest that p53 plays a major role in the progression
      of carcinoma of the small intestine, whereas the role of K-ras mutation is much
      less significant.

PMID- 11836596
TI  - Prediction of cell kill kinetics of anticancer agents using the collagen gel
      droplet embedded-culture drug sensitivity test.
AB  - A vital component of chemotherapy is selecting effective anticancer agents for
      the patient and determining an appropriate dose and administration regimen.
      Prediction of the drug sensitivity of each patient and cell kill kinetics of the
      drug may improve the outcome of treatment and avoid unnecessary dosing of the
      drug. For this reason, the development and clinical application of anticancer
      drug sensitivity tests and cell kill kinetics tests which successfully reflect
      clinical outcomes are required. In the present study, we tried to establish a
      cell kill kinetics test through the use of new anticancer agents: paclitaxel,
      docetaxel, SN-38, vinorelbine, and gemcitabine. These agents were studied at
      concentrations close to their clinical doses using a collagen gel droplet
      embedded-culture drug sensitivity test (CD-DST). It is thought that the
      mechanism, by which the anticancer agents used in this study exert their effects
      is dependent on the cell cycle; however, the cell kill kinetics of these agents
      at clinical concentrations has not yet been clarified in vitro. We investigated
      the drug sensitivity and cell kill kinetics of these new anticancer agents
      against a human colon cancer strain. Results of this study suggest that the test
      method established by us can predict drug sensitivity and cell kill kinetics of
      the agents, and can be a useful tool in deciding appropriate treatment regimen
      for individual patients.

PMID- 11836598
TI  - Clinicopathologic characteristics of superficial spreading type squamous cell
      carcinoma of the esophagus.
AB  - Intraepithelial carcinoma concomitant with the main tumor is a conspicuous
      feature in squamous cell carcinoma (SCC) of the esophagus. The aim of the current
      study was to clarify the clinicopathologic features of superficial spreading type
      SCC of the esophagus. Ninety-seven patients with esophageal squamous cell
      carcinoma, whose main carcinoma is invading the mucosa or submucosa, were
      investigated in the current study. The clinicopathologic features were compared
      between 13 cases demonstrating a superficial spreading type carcinoma in which
      the spreading size of the tumor was 5 cm or more in length and 84 cases with the
      size less than 5 cm. Although no significant difference was observed regarding
      lymphatic invasion, venous invasion, intramural metastasis and lymph node
      metastasis, the survival rate of patients with superficial spreading type
      carcinoma was much better than that of patients with ordinary superficial
      carcinoma of the esophagus. Coexistence of superficial spreading type carcinoma
      may be correlated with a favorable prognosis of patients with superficial
      esophageal SCC.

PMID- 11836597
TI  - Using technetium-99m-tetrofosmin scan to predict chemotherapy response of
      malignant lymphomas, compared with P-glycoprotein and multidrug resistance
      related protein expression.
AB  - The ability of technetium-99m tetrofosmin (Tc-TF) scan to predict chemotherapy
      response in malignant lymphomas (ML) was compared with the predictive ability of
      P-glycoprotein (Pgp) and multidrug resistance related protein (MRP) expression.
      Before chemotherapy, 25 ML patients were enrolled in this study. Scans were
      performed 10 min after intravenous injection of Tc-TF. Immunohistochemical
      analyses were performed on ML specimen sections to evaluate Pgp and MRP
      expression. Chemotherapy response was evaluated in the first 1-2 years after
      completion of chemotherapy. Based on Tc-TF scan results, the mean tumor-to
      background (T/B) ratio of the 15 patients with good response (3.23 +/- 0.56) was
      significantly higher than that of the 10 patients with poor response (1.18 +/-
      0.11). All 15 patients with good response had positive Tc-TF scan results but
      negative Pgp and MRP expression. All 10 patients with poor response had negative
      Tc-TF scan results but positive Pgp or MRP expression. No significant differences
      in the incidences of good and poor response results were found for patients with
      Hodgkin's disease versus non-Hodgkin's lymphoma, with stage I-II versus stage III
      IV, with age > 40 versus age < or = 40 years, or with B symptoms versus without B
      symptoms. Tc-TF scan results, which may represent either Pgp or MRP expression,
      accurately predict chemotherapy response in patients with ML.

PMID- 11836599
TI  - Adenosquamous cell carcinoma arising from the papilla major.
AB  - A 47-year-old man was admitted to hospital with complaint of general fatigue.
      Shortly before the admission a suspected obstructive jaundice was diagnosed at a
      local hospital. On admission, the physical examination was significant for
      jaundice; total bilirubin was 6.43 mg/dl. The tumor marker CA19-9 was 2056 U/ml.
      Endoscopic retrograde cholangiopancreatography (ERCP) was performed and showed
      dilatation of common bile duct and main pancreatic duct, accompanied with an
      endoscopic naso-biliary drainage (ENBD) in order to reduce the jaundice. The
      duodenoscopy showed enlarged and deformed papilla. Hypotonic duodenography showed
      a filling defect at the medial side of the second portion of the duodenum.
      Ultrasonography (US) showed a hyperechoic lesion, sized 15 mm in diameter, at the
      pancreas head with dilatation of biliary tract and main pancreatic duct. An
      abdominal enhanced CT scan showed a mass sized 15 mm at the lower edge of the
      common bile duct. A selective hepatic arteriography showed no special finding. We
      performed a pancreatoduodenectomy with dissection of the lymph nodes. The tumor,
      sized 22x15x20 mm, was white colored and solid on the papilla. Histopathological
      inspection of the specimen showed an adenosquamous cell carcinoma of the bile
      duct in the papilla. The tumor was found to infiltrate the neighboring pancreas
      and to contain metastasis in lymph nodes in the hepatoduodenal ligament, post
      pancreaticoduodenal and para-aortic lymph nodes. This is the first report on a
      case of adenosquamous carcinoma of the papilla major.

PMID- 11836600
TI  - Comparison of 18F-fluoro-2-deoxyglucose positron emission tomography and gallium
      67 citrate scintigraphy for detecting malignant lymphoma.
AB  - This study evaluates and compares the accuracy of positron emission tomography
      with 18F-fluoro-2-deoxyglucose (FDG-PET) and gallium-67 citrate (Ga-67)
      scintigraphy in identifying disease sites in patients with malignant lymphoma at
      initial diagnosis or relapse. Histology subgroups included low (n=5),
      intermediate (n=6), high-grade (n=5) non-Hodgkin's lymphoma (NHL) and Hodgkin's
      disease (HD) (n=14). Ann-Arbor staging included 7 patients in stage I, 8 in stage
      II, 9 in stage II, 6 in stage IV and 11 extra-nodal. In this study, before any
      therapy, 25 contemporaneous FDG-PET and Ga-67 scintigraphies were performed on
      patients with either NHL (16) or HD (14). One hundred and eleven sites of disease
      were correlated on a site-by-site basis in corresponding areas of FDG-PET and Ga
      67 scintigraphy. Discordant FDG-PET and Ga-67 scintigraphic findings were
      correlated with CT/MRI and clinical evaluation. FDG-PET detected malignant
      lymphoma in 24/25 patients (sensitivity: 96.0%). There was a false-negative FDG
      PET result in only 1 patient with low-grade gastric malignant lymphoma. Ga-67
      scintigraphy detected malignant lymphoma in 18/25 patients (sensitivity: 72.0%).
      There were false-negative Ga-67 scintigraphic results in 4 cases with low-grade
      non-Hodgkin's lymphoma, 2 cases with bone or bone marrow involvement, and 3
      smaller disease sites. FDG-PET upstaged 6 patients in whom Ga-67 scintigraphy
      detected disease sites partially. In imaging lymphoma prior to therapy, FDG-PET
      had a higher sensitivity and detected significantly more disease sites when
      compared with Ga-67 scintigraphy in the initial evaluation of this group of
      patients. Upstaging of patients with FDG-PET may result in a change in treatment
      strategy. However, evaluation of the final sensitivity, specificity and accuracy
      of these imaging modalities will need a further study with a larger patient
      number.

PMID- 11836601
TI  - Polymorphism analysis of CYP3A5 in myeloid leukemia.
AB  - The human cytochrome P450 (CYP) metabolizes more than 100 structurally diverse
      exogenous and endogenous molecules. The CYP3A5 is a major P450 enzyme in the
      liver and represents 50% of the total hepatic CYP3A content in people expressing
      CYP3A5. The single nucleotide polymorphisms in CYP3A5*3 and CYP3A5*6 that
      resulted in the absence of CYP3A5 from tissues were noted in some people.
      Polymorphisms of potential relevance to leukemia and myelodysplastic syndrome
      (MDS) have been described for various CYP. The bone marrow and/or peripheral
      blood from 188 acute myeloid leukemia (AML) patients, 101 chronic myeloid
      leukemia (CML), 40 MDS, and 270 normal controls were analyzed by a PCR-RFLP assay
      to evaluate the association of the CYP3A5 polymorphisms with myeloid leukemia.
      Our data showed that 15/188 (8%), 8/101 (7.9%), and 3/40 (7.5%) of the patients
      (i.e., 188 AML, 101 CML, 40 MDS) were CYP3A5*1/*1; 88/188 (46.8%), 47/101
      (46.5%), and 20/40 (50%) were CYP3A5*1/*3; and 85/188 (45.2%), 46/101 (45.5%),
      and 17/40 (42.5%) carried the CYP3A5*3/*3 genotype, respectively. CYP3A5*6 was
      not found in any of the patients' specimens. Similar frequencies of CYP3A5*3 were
      observed in the leukemic patients and normal controls. Consequently, the finding
      suggests that the CYP3A5 polymorphism was not associated with the risk of myeloid
      leukemia.

PMID- 11836602
TI  - Chronological changes of causes of death and distant metastasis in hepatocellular
      carcinoma.
AB  - The diagnostic approaches, mode of therapies, frequencies of distant metastasis
      and causes of death in 139 patients with hepatocellular carcinoma (HCC) between
      1976 and 1998 were studied by dividing the total study duration into three
      periods. The period between 1976-1980 (period I) was characterized by the absence
      of periodic follow-up of the patients with chronic liver diseases, and operation
      was the only therapeutic choice for HCC. During 1981-1986 (period II), periodic
      screening of patients with chronic liver diseases was started using
      ultrasonography, and transarterial embolization became a second choice of therapy
      along with operation. Period III (1986-1998) was characterized by the
      availability of facilities to make definitive diagnosis of HCC using small-gauge
      cutting needle biopsy under sonographic guidance. Data from our study show that
      along with the advancement of new and invasive diagnostic and therapeutic
      approaches, the frequency of death due to gastrointestinal bleeding decreased,
      whereas, the frequency of death due to respiratory failure resulting from
      pulmonary metastasis increased. Patients treated with transcatheter arterial
      embolization were more prone to develop pulmonary metastasis. These data show
      that patients with HCC undergoing invasive therapies should be checked for
      distant metastasis in addition to intrahepatic recurrence of HCC.

PMID- 11836603
TI  - Suppression of tumor growth and pulmonary metastasis in murine osteosarcoma using
      gene therapy.
AB  - We evaluated the effect of gene therapy in the murine osteosarcoma cell line,
      LM8, which preferentially metastasizes to the lungs. LM8 cells were transduced
      with the gene for a herpes simplex virus thymidine kinase (HSV-tk) or Escherichia
      coli beta-galactosidase (lacZ). We investigated the cytotoxicity of LM8 cells
      bearing an HSV-tk gene after treatment with ganciclovir (GCV). LM8 cells bearing
      an HSV-tk gene were more sensitive than non-transduced cells. The remarkable
      inhibition of tumor growth and pulmonary metastases was confirmed in vivo. Our
      findings indicated that GCV kills tumor cells transduced with HSV-tk in vitro and
      in vivo.

PMID- 11836604
TI  - Prognostic significance of heat shock protein 27 (HSP27) in patients with oral
      squamous cell carcinoma.
AB  - Heat shock proteins (HSPs) have been defined as proteins induced by heat shock
      and other environmental and pathophysiologic stress. Heat shock protein 27
      (HSP27) is one of the small heat shock proteins. HSP27 is implicated in protein
      protein interactions such as folding, translocation, and prevention of
      inappropriate protein aggregation. Many of their functions suggest that they play
      important roles in cancers. Archival tissues from 40 patients with oral squamous
      cell carcinoma who received primary surgical resection were examined for HSP27 by
      immunohistochemistry and correlated with clinical stage, lymph node metastasis,
      histological grade and survival period. HSP27 expression was positive staining
      (+) in 20 (50%), weak or negative staining (-) in 20 (50%) of total 40 cases.
      There was no correlation between HSP27 expression and clinical stage, lymph node
      metastasis and histological grade. However, when compared with
      clinicopathological features, the expression of HSP27 correlated inversely with
      survival period. This study suggests that the expression of HSP27 is frequently
      promoted in patients with oral squamous cell carcinoma and should be considered
      an independent prognostic factor of oral squamous cell carcinoma patients.

PMID- 11836605
TI  - L-myc restriction fragment length polymorphism and histological pattern of
      invasion in lung adenocarcinoma.
AB  - It is still controversial whether restriction fragment length polymorphism (RFLP)
      of the L-myc proto-oncogene is correlated with the prognosis in lung cancer
      patients or not. On the other hand, we have shown that the histological pattern
      of invasion is correlated with the prognosis of surgically treated patients of
      lung adenocarcinoma. In this study, the L-myc RFLP was compared with the
      histological pattern of invasion and the prognosis in 63 Japanese lung
      adenocarcinoma patients to evaluate the L-myc RFLP as a prognostic marker.
      Although the histological pattern of invasion was correlated with the prognosis,
      no correlation was observed between the L-myc RFLP and the prognosis. No
      association was found between the L-myc RFLP and the histological pattern of
      invasion in this study. Our results showed that the L-myc RFLP is not a strong
      prognostic marker compared with histologic pattern of invasion in lung
      adenocarcinoma.

PMID- 11836606
TI  - Intratumoral level of gonadotropin-releasing hormone in ovarian and endometrial
      cancers.
AB  - Gonadotropin-releasing hormone (GnRH) produced within ovarian cancers and
      endometrial cancers acts as a negative autocrine regulator in their growth. To
      provide a potential association of GnRH content with the presence of GnRH
      receptor, we have evaluated GnRH levels in human gynecologic carcinomas and
      compared them to those in normal tissues. Surgically removed tumors and normal
      tissues had been screened for GnRH receptor expression before analysis. GnRH was
      determined by a radioimmunoassay and a high-performance liquid chromatography in
      peptide extracts. GnRH levels for ovarian cancers (n=25, range 0.01- 0.99 pg/mg
      protein, with a mean +/- SD of 0.37 +/- 0.28 pg/mg protein) and for endometrial
      cancers (n=12, range 0.01-0.19, 0.13 +/- 0.074 pg/mg protein) were significantly
      higher than those for normal ovaries (n=11, range 0.007-0.195, 0.10 +/- 0.06
      pg/mg protein) (P=0.003) and endometria (n=7, range 0.01-0.09, 0.049 +/- 0.029
      pg/mg protein) (P=0.014), respectively. The GnRH levels in these cancers were not
      different between GnRH receptor-positive specimens (20 ovarian cancers and 9
      endometrial cancers) and -negative specimens (5 ovarian cancers and 3 endometrial
      cancers). In contrast, GnRH was <0.001 pg/mg protein in all 13 uterine cervical
      carcinomas bearing no GnRH receptor. These data demonstrate that the neoplastic
      ovaries and endometria that frequently express GnRH receptor have the capacity to
      produce excessive amount of GnRH regardless of whether GnRH receptor is evident.

PMID- 11836607
TI  - Uptake of indium-111-labeled human polyclonal immunoglobulin G in pancreatic
      cancer: in vivo and in vitro studies.
AB  - Radiolabeled human non-specific polyclonal immunoglobulin G (HIG), is used for
      the diagnosis of inflammation/infection. Focal uptake of HIG in malignant lesions
      has also been reported. We investigated the diagnostic value of In-111-HIG in
      patients with known pancreatic cancer. Fourteen consecutive patients with
      histologically verified pancreatic cancer were included in this prospective
      study. Four of them had undergone potentially curative surgery for their primary
      cancer. Eight patients had liver metastases. Planar and SPECT images of the
      abdomen were performed after administration of In-111-HIG (74-92 MBq).
      Scintigraphic results were compared to conventional imaging by means of CT
      scanning. In addition, In-111-HIG uptake was investigated in a panel of four
      representative human pancreatic cancer cell lines. Primary pancreatic tumors were
      visualized by In-111-HIG in 6 out of 10 patients (sensitivity 60%), while 1 was
      false positive. In comparison, CT scanning was true positive in 9 out of 10
      patients (sensitivity 90%), and no false positive. Visualization of liver lesions
      by means of In-111-HIG was possible in 6 out of 8 patients (sensitivity 75%),
      while 1 was false positive. In vitro studies revealed only minimal uptake of In
      111-HIG into cells (about 3% of activity). Our data demonstrate that In-111-HIG
      is able to visualize pancreatic primary cancers as well as liver metastases.
      However, the minimal uptake into tumor cells, as shown in vitro, suggests non
      specific tumor related inflammatory reactions, increased vascular permeability,
      release of indium from In-111-DTPA-labeled antibody and local retention to be
      responsible for visualization of the tumor site.

PMID- 11836608
TI  - Changes in natural killer cell activity by external radiotherapy and/or
      brachytherapy.
AB  - Our purpose in this study was to determine the influence of radiotherapy,
      especially brachytherapy, on the activity of natural killer cells (NK). We
      examined changes in NK activity before and after radiotherapy in 27 patients who
      underwent radiotherapy with or without brachytherapy, comprising of 16 cases of
      cervical cancer (three recurrences), 5 of prostate cancer, 4 of esophageal cancer
      and 2 of tongue cancer. Fourteen intracavitary procedures (for 13 cervical
      cancers and 1 esophageal cancer) and 10 interstitial brachytherapy (for 3 cases
      of recurrent cervical cancer, 5 of prostate cancer and 2 of tongue cancer) were
      performed with Ir-192 microSelectron HDR and Selectron Cs-137. External
      radiotherapy consisted of 10 MV X-ray administration for 13 cases of cervical
      cancer and 4 of esophageal cancer. The number of white blood cell was reduced by
      radiotherapy from 5065 +/- 2002 count/ml to 4281 +/- 1392 count/ml (p=0.02), that
      of lymphocytes from 1518 +/- 817 to 762 +/- 409 /ml (p<0.0001), and that of CD
      16+ cells from 274 +/- 197 to 14 +/- 96 (p=0.03). No significant change was
      observed in the number of CD 56+ cells (274 +/- 166 to 211 +/- 153 /ml). Overall
      NK activity was reduced by radiotherapy from 37 +/- 19% to 30 +/- 19% (p=0.001).
      External radiotherapy with or without brachytherapy reduced NK activity from 33
      +/- 18% to 23 +/- 16% (p=0.004). However interstitial brachytherapy produced
      little change in NK activity from 42 +/- 18 to 39 +/- 19%). Radiotherapy reduced
      the number of white blood cell, lymphocyte and CD 16+ cells. Although external
      radiotherapy suppressed NK activity, only brachytherapy showed little influence
      on NK activity alteration.

PMID- 11836609
TI  - Thermochemotherapy of a human salivary adenocarcinoma cell line.
AB  - We report on thermochemotherapy in a human salivary gland adenocarcinoma cell
      line. Hyperthermia reduced the survival rate to 50 and 20% by heating at 43
      degrees C for 40 and 60 min, respectively, and is by itself useful in human
      salivary gland carcinoma treatment. Adriamycin, cisplatin, and mitomycin C can
      possible be used clinically, while bleomycin and 5-fluorouracil cannot, to treat
      this carcinoma. The optimal temperature was considered to be 41 degrees C in
      adriamycin, 42 degrees C in cisplatin, 37 degrees C in mitomycin C, and 42
      degrees C in bleomycin in the thermochemotherapy. Thermochemotherapy is a useful
      tool in the treatment of human salivary gland carcinoma cells, but it is
      necessary to select the best anticancer drugs and the optimal temperature for
      optimal success using this treatment.

PMID- 11836610
TI  - Leucine zipper structure of TSC-22 (TGF-beta stimulated clone-22) markedly
      inhibits the anchorage-independent growth of salivary gland cancer cells.
AB  - Several investigators have demonstrated that TGF-beta stimulated clone-22 (TSC
      22) regulates cell growth and differentiation, and cell death. TSC-22 is a
      putative transcriptional regulator containing a leucine zipper-like structure and
      a nuclear export signal. We previously showed the cytoplasmic localization of TSC
      22 and the nuclear translocation of TSC-22 concomitant with induction of
      apoptosis in salivary gland cancer cells. In the present study, we attempted to
      identify the active domain of TSC-22 protein that regulated the biological
      functions of TSC-22. We constructed three mammalian expression vectors, which
      could produce full length TSC-22 only in cytoplasm, the leucine zipper structure
      of TSC-22 in both cytoplasm and nucleus, and the leucine zipper structure only in
      nucleus. Then, we transfected a salivary gland cancer cell line, HSG with these
      expression vectors, and investigated the growth profile of the transfectants.
      None of the TSC-22 constructs inhibited the monolayer growth and the anchorage
      dependent colony formation of HSG cells. However, the leucine zipper structure of
      TSC-22 markedly inhibited the anchorage-independent colony formation of HSG cells
      (p<0.001; one way ANOVA). Full length TSC-22 also suppressed the anchorage
      independent colony formation of HSG cells, although the effect of full length TSC
      22 was much lower than those of the leucine zipper constructs. These observations
      suggest that the leucine zipper structure in TSC-22 protein is an active domain
      that negatively regulates the growth of salivary gland cancer cells.

PMID- 11836611
TI  - Predictive value of estrogen receptor status as assessed by ligand-binding assay
      in patients with early-stage breast cancer treated with breast conserving surgery
      and radiation therapy.
AB  - It is important to determine which factors are predictive for the prognosis of
      patients treated with breast conserving surgery (BCS) and radiation therapy (RT)
      in order to make a decision as to the adjuvant treatment. Although estrogen
      receptor (ER) is known to be a predictive marker for antiestrogens in breast
      cancer, the prognostic effect of hormone receptors has not been fully analyzed in
      Japanese breast cancer patients treated with BCS and RT. A total of 153 breast
      cancer patients having up to three positive nodes in the axilla as identified
      histologically and treated with both BCS and RT with or without systemic therapy
      were enrolled in this study. All tumors were measured for ER and progesterone
      receptor (PR) using ligand-binding assay (LBA). ER was inversely related to
      patients' age, however, PR was not related to any clinical features. When ER was
      classified into negative, weakly positive and strongly positive categories, with
      cut-off levels of zero and 50 fmol/mg protein, the relapse-free survival (RFS)
      was significantly better in patients with tumors having strongly positive ER than
      in patients with tumors having negative ER. Multivariate analysis revealed that
      ER as well as nodal status, was an independent predictive factor for RFS,
      however, PR was not. As a result, we believe that ER measured by LBA is valuable
      for predicting prognosis of early-stage breast cancer patients treated with BCS
      and RT.

PMID- 11836612
TI  - Synergistic antitumour effect of a combination of toremifene and interferon-alpha
      on ZR-75-1 human breast cancer cells: dependence on interferon-alpha subtype.
AB  - We investigated the effect of toremifene, interferon-alpha2a, interferon-alpha2b
      and interferon-alpha2c, singly and in combination for their effect on the growth
      of ZR-75-1 human breast cancer cells. Median effect analysis was used to
      determine synergistic or additive effects. Anti-proliferative studies showed that
      the growth of ZR-75-1 cells was inhibited to a greater extent by combination
      treatment with toremifene plus interferon-alpha2a, resulting in a synergistic
      interaction (CI <1) for all concentrations tested. A combination of toremifene
      plus interferon-alpha2b resulted in a synergistic interaction (CI <1) for the two
      highest concentrations of toremifene (10(-6) and 10(-7) M) and an additive effect
      (CI approximately equal to 1) for the lower concentrations (10(-8) to 10(-10) M).
      When toremifene was combined with interferon-alpha2c no additive or synergistic
      interaction was determined.

PMID- 11836613
TI  - Q356R and S1512I are BRCA1 variants that may be associated with breast cancer in
      a Cypriot family.
AB  - A molecular study was performed on BRCA1 and BRCA2 genes in a Cypriot family,
      with a history of both male and female breast cancers. Three variants were
      detected in the BRCA1 gene, two of which are missense mutations at nucleotide
      positions 1186 in exon 11 (Q356R), and 4654 in exon 15 (S1512I). The third
      variant is a polymorphism at position 2430 in exon 11 (771L). Similarly in the
      BRCA2 gene two variants were detected: a missense mutation at position 1342, exon
      10 (H372N), and a polymorphism at position 3624 in exon 11 (1132K). Since these
      BRCA2 variants appear to be polymorphisms in the Cypriot population, we suggest
      that the two BRCA1 mutations, Q356R and S1512I, may be related to the breast
      cancer phenotype.

PMID- 11836615
TI  - Expression of the genes of methyl-binding domain proteins in human gliomas.
AB  - DNA methylation is the most common epigenetic alteration in tumor genomes and
      might result in transcriptional repression of tumor suppressor genes. Moreover,
      recent results have demonstrated that both specific methylation patterns and
      functional components of the mismatch repair system are involved in the
      development of therapy resistance of tumor cells. Here we investigated the
      expression of the genes of methyl binding domain containing proteins (MBD) in
      human gliomas both in vivo and in vitro. We found expression of MBDs including
      MBD1, MBD2, MBD3 and MBD4/MED1 in all glioma cell lines and glioma biopsies. No
      differences existed in vitro with regard to individual MBDs and individual cell
      lines. In vivo, MBD1 and MBD2 were also expressed in all biopsies with only minor
      differences between individual tumors. MBD3 and MBD4/MED1, however, showed a
      correlation of expression with the grade of malignancy. Astrocytomas and
      anaplastic astrocytomas showed a weak expression compared with a high expression
      in glioblastoma multiforme.

PMID- 11836614
TI  - Cyclic AMP-dependent secretion of Ca 19-9 by LS174T human colon carcinoma cells.
AB  - Prolonged increase of cyclic adenosine-monophosphate (cAMP) level in culture
      medium of a human colon cancer cell (LS174T) inhibits cellular growth and
      stimulates Ca 19-9 expression. The raise in cAMP level was produced by dibutyryl
      cyclic AMP (DBcAMP) or by forskolin an agent acting at the level of cAMP
      generation. Both these agents in a range of concentration between 10(-3)-10(-5) M
      have an inhibitory effect on the growth which is dose and time dependent. The
      inhibition was reversible as demonstrated by complete restoration of cell growth
      soon after the withdrawal of the substances from the culture medium. When cAMP
      levels in culture medium was raised, an increase in Ca 19-9 expression was
      observed and it appears that cyclic nucleotides have at least two effects: the
      first to cause rapid release of already synthesized Ca 19-9 and second to
      stimulate new antigen synthesis. The findings of the present study demonstrated
      that LS174T cells are unable to proliferate upon sustained accumulation of
      intracellular cyclic AMP suggesting the use of strategies able to increase cAMP
      levels for therapy of colon cancer. Furthermore, the finding that cAMP may also
      be a regulator of Ca 19-9 synthesis and release indicates the utility of cell
      line LS174T as a model for studies on the mechanism of synthesis and secretion of
      specific tumoral markers in colon cancer.

PMID- 11836616
TI  - Effects of growth factors on growth and radiation sensitivity of the human breast
      cancer cell line T-47D.
AB  - Different growth factors are supposed to be involved in evolution of breast
      cancer. Radiation therapy is used in treatment of breast cancer patients, and the
      possible relationships between the influence of growth factors on cells and their
      radiation sensitivity are therefore of interest. Cell growth and radiation
      sensitivity of the human oestrogen and progesterone receptor positive cell line T
      47D were investigated following exposure to the growth factors IGF-1, TGF-alpha
      and TGF-beta. Experiments were done with standard medium and in growth factor
      defined medium. Changes in cell cycle distribution were investigated by flow
      cytometry. The cell growth was significantly decreased by removal of growth
      factors in the culture medium, an effect which partly could be reversed by
      supplementation of growth factors. The growth factors decreased the cellular
      doubling time in standard medium, but to a smaller extent than seen in growth
      factor defined medium. The radiation sensitivity and plating efficiency were
      slightly affected by growth factor defined versus standard growth conditions.
      Additional growth factor exposure was able to some extent to change the radiation
      sensitivity, mainly by effects due to changes in repair of sublethal damage. Only
      minor changes were seen in phase distribution of these cells. Cellular growth was
      dependent on presence of different growth factors, and changes in growth factor
      conditions greatly influenced the cellular doubling time in vitro. Corresponding
      changes in radiation sensitivity were minor for doses relevant for radiation
      therapy.

PMID- 11836617
TI  - Intracystic breast carcinoma in a male: Unusual case presentation and literature
      review.
AB  - Breast carcinoma in males is rare and accounts for 0.5-1.5% of all breast
      carcinomas. Intracystic breast carcinoma is distinctly uncommon and represents
      approximately 5-7.5% of all breast cancers in males. On physical examination and
      radiologic imaging, these lesions often appear benign; however, the presence of
      an intracystic solid component is typical and should raise the suspicion of
      carcinoma. We report an unusual case of intracystic breast carcinoma presenting
      in a male and review the literature.

PMID- 11836618
TI  - Expression and amplification of cyclin D1 in primary breast carcinomas:
      relationship with histopathological types and clinico-pathological parameters.
AB  - Overexpression and amplification of cyclin D1 were investigated by
      immunohistochemistry and differential polymerase chain reaction (dPCR) in 440
      formalin-fixed primary breast carcinoma tissues. Overexpression of cyclin D1 was
      detected in 60% (263/440) and amplification of cyclin D1 was noted in 27%
      (119/440) of the primary breast carcinomas. Molecular analysis demonstrated that
      cyclin D1 was amplified in 30% (7/23) of the comedo DCIS, 22% (9/41) of the
      comedo DCIS and 32% (13/41) of the adjacent invasive ductal carcinomas, 30%
      (82/270) of the invasive ductal carcinomas, 27% (9/33) of the invasive lobular
      carcinomas, 19% (4/21) of the colloid carcinomas and 13% (2/15) of the medullary
      carcinomas. Cyclin D1 was amplified in 11% (2/19) of the invasive ductal
      carcinomas but not in the adjacent non-comedo DCIS lesions. Our observation
      showed that cyclin D1 was strongly positive in 61% (14/23) of the comedo subtype,
      61% (11/18) of the non-comedo subtype, 59% (24/41) of the comedo DCIS and 63%
      (26/41) of the adjacent invasive ductal carcinomas, 53% (10/19) of the non-comedo
      DCIS and 58% (11/19) of the adjacent invasive lesions, 58% (157/270) of the
      invasive ductal carcinomas, 73% (24/33) of the invasive lobular carcinomas, 52%
      (11/21) of the colloid carcinomas and 27% (4/15) of the medullary carcinomas. A
      significant association was observed between in situ components and adjacent
      invasive lesions for cyclin D1 expression (p<0.05) and amplification (p<0.05). A
      significant relationship was noted between amplification of cyclin D1 and lymph
      node metastases (p<0.05) but not with histological grade (p>0.05), estrogen
      receptor status (p>0.05) and proliferation index (Ki-67 and PCNA) (p>0.05).
      However, overexpression of cyclin D1 was statistically associated with well
      differentiated tumors (p<0.05) and estrogen receptor positivity (p<0.05). No
      relationship was seen with nodal status (p>0.05) and proliferation index (Ki-67
      and PCNA) (p>0.05). These observations suggest that tumors positive for cyclin D1
      protein may have features of good prognosis but amplification of cyclin D1 gene
      could be an indicator of tumors with poor prognostic features. Although majority
      of the Malaysian patients belong to younger age group (<50 years old),
      amplification and expression of cyclin D1 was not statistically associated with
      patient age (p>0.05). These observations indicate that amplification and up
      regulation of cyclin D1 may be independent of patient age. Moreover,
      overexpression and amplification of cyclin D1 in preinvasive, preinvasive and
      adjacent invasive lesions, and invasive carcinomas suggest that the gene may play
      an important role in early and late stages of breast carcinogenesis.

PMID- 11836619
TI  - Loss of heterozygosity and microsatellite instability in male breast cancer.
AB  - Male breast cancer is a relatively rare disease that represents about 1% of all
      male malignancies. Its genetic basis has received little attention. Allelic
      imbalance, reflected by change in microsatellite repeat number (MSI) or loss of
      heterozygosity (LOH), is thought to play an important role in carcinogenesis. In
      this study we have examined DNA extracted from paraffin tissue from 15 patients
      treated for male breast cancer, for evidence of such abnormalities, at 20
      different loci across the genome. Polymerase chain reaction amplified products of
      normal and tumor DNA pairs were compared by electrophoresis on Spreadex gels. MSI
      was detected in 5 patients; at a single site in 2 cases and at 3, 7 and 9 sites
      in another 3 cases. LOH was seen in 8 cases (53%); at more than one site in 4 of
      these. Two patients had allelic variation at 56 and 62% of assessable sites. The
      most unstable loci were D2S441 (33%) and D13S325 (27%). These observations
      indicate that replication errors and allelic loss characterise male breast cancer
      tissue in much the same way as they do in women. More studies will be needed to
      establish whether these are random lesions or whether there are specifically
      affected sites that occur in both male and female breast cancer.

PMID- 11836620
TI  - Pentoxifylline inhibits perforin-dependent natural cytotoxicity in vitro.
AB  - Pentoxifylline (PTX) is commonly used in peripheral blood vessel diseases,
      however it has also been found to decrease the level of proinflammatory cytokines
      such as IL-12, TNF-alpha and IFN-gamma. Moreover, some authors reported that PTX
      suppresses spontaneous cytotoxicity of peripheral blood mononuclear cells (PBMC)
      in vitro. It could influence the mechanism of killing target cells by PBMC. For
      this reason we evaluated the influence of PTX on spontaneous cytotoxicity of PBMC
      against K562 and CaSki cell lines. Subsequently, we compared this effect to that
      evoked by dexamethasone, one of the most effective anti-inflammatory drugs. Our
      study revealed that PTX inhibits natural cytotoxicity preferentially through
      inhibition of perforin-mediated cell membrane damage, without a statistically
      significant influence on apoptosis induction. Furthermore, pentoxifylline
      inhibits natural cytotoxicity as effectively as dexamethasone. However, the
      result of PTX inhibitory influence is observed much earlier than that of
      dexamethasone. Currently PTX is commonly used in diseases that occur more
      frequently in elderly patients. We suggest that PTX, inhibiting perforin
      dependent PBMC cytotoxic activity, could weaken anti-cancer action of immune
      system thus accelerating the progress of neoplasm formation in these patients.

PMID- 11836621
TI  - IL-12 or IL-15, unlike IL-2, does not interact with histamine in augmenting
      cytotoxicity of splenocytes against melanoma cells and YAC-1 cells.
AB  - It has been suggested that histamine by its ability to downregulate the
      production of macrophage-derived reactive oxygen species might effectively
      potentiate the cytotoxic activity of cytokine-stimulated NK cells. Histamine thus
      reverses negative regulation of NK cells treated with IL-2 and IFN-alpha in the
      presence of macrophages. We confirm that histamine potently enhances cytotoxic
      activity of IL-2-stimulated NK cell-enriched splenocytes admixed with macrophages
      against B16F10 melanoma cells and YAC-1 cells. This stimulation results in
      production of high amounts of INF-gamma and TNF-alpha. Interestingly, IL-15 by
      itself promotes production of reactive oxygen species. Although histamine
      decreased reactive oxygen species production from the cultures of IL-15
      stimulated NK cell-enriched splenocytes admixed with macrophages, it did not
      potentiate the cytotoxicity of IL-15. Further, we demonstrate that histamine
      mediated potentiation of cytotoxicity is not applicable to IL-12, another potent
      activator of NK cell activity.

PMID- 11836622
TI  - Rearrangement of p53 gene with overexpressed p53 protein in primary cervical
      cancer.
AB  - The frequency of p53 mutations is low and there is evidence of p53 protein
      overexpression even without p53 mutations in cervical cancers. This suggests that
      alternative mechanisms other than p53 mutation could be responsible for
      tumourigenesis of the uterine cervix. Therefore, an attempt has been made in the
      present investigation to analyze mutation and rearrangement of p53 gene in
      primary cervical cancers. The results indicated absence of mutation and presence
      of rearrangement in about 35% of cervical cancer patients. However, p53
      overexpression in 50% of patients was demonstrated by immunohistochemistry and
      Western blot analysis. Further, rearrangement of p53 has been correlated with p53
      mRNA and p53 protein status. The results indicated presence of overexpressed p53
      protein in the samples with rearranged p53 gene. Thus, it is presumed that
      rearrangement of p53 might lead to production of defective p53 protein by
      affecting the level of p53 protein and this might have a role in the process of
      tumourigenesis. This study reports for the first time rearrangement of p53 in
      cervical cancers.

PMID- 11836623
TI  - Intensified ABVP chemotherapy for the primary treatment of Hodgkin's disease.
AB  - This report describes the results of a multicenter study designed to determine
      the efficacy and toxicity of a novel combination (ABVP) in patients with newly
      diagnosed Hodgkin's disease. The ABVP protocol is a modification of ABVD in which
      prednisone is substituted for DTIC. In order to attempt an increase in drug
      intensity, doxorubicin, bleomycin and vinblastine were administered on days 1 and
      8 of each cycle, and a new cycle began on day 22. Patients who developed
      phlebitis were allowed to receive the drugs every two weeks. Patients with bulky
      mediastinal disease received involved field radiation therapy after chemotherapy.
      Fifty-one patients were treated. Complete remission was achieved in 40 patients
      (78%). Actuarial failure-free survival in 55 months was 59%, and overall survival
      was 81%. The overall survival for the 32 patients treated with the intensified
      regimen was higher than that for those who switched to the bi-weekly schedule
      (89% vs. 68%, p=0.03). ABVP appears to be equivalent to ABVD. The higher overall
      survival rate in patients treated every 21 days suggests that this intensified
      schedule might be more effective. The placement of a Port catheter is
      recommended, due to the high incidence of phlebitis.

PMID- 11836624
TI  - Schizophrenia: a genetic perspective (review).
AB  - Schizophrenia is a complex neurodevelopmental disorder characterized by mental
      dysfunction across multiple domains of the brain. It affects 1% of world's
      general population and the nature of neurobiological lesions in the schizophrenic
      brain are not known. Although the exact etiology of the disorder is not
      understood, twin, family and adoption studies have provided consistent evidence
      that genetic factors play a major role in the pathogenesis. A genome-wide genetic
      linkage screen identified loci on chromosomes 1, 2, 4, 5, 6, 7, 8, 9, 10, 11, 13,
      15, 18, 22 and the X with positive lod scores, thus excluding a single major
      locus for schizophrenia. Association studies have generated disappointing results
      in identifying the susceptible DNA sequence variants and the anticipation
      hypothesis on trinucleotide repeat expansion provided equivocal results or lack
      of enthusiasm. Although there are no biological markers at present, the recent
      finding that human endogenous retrovirus is activated in cerebrospinal fluid as
      well as in the postmortem schizophrenic brain may change our understanding of the
      etiopathogenesis of this disease. Meanwhile, treatment with newly developed anti
      psychotic drugs combined with educational and cognitive rehabilitation procedure
      may help the patients to cope with the illness.

PMID- 11836625
TI  - RFX-B, a MHC class II transcription factor, suppressed in human colorectal
      adenocarcinomas.
AB  - Regulatory factor X (RFX) is an essential MHC class II transcription factor and
      contains three distinct subunits of which RFX-B is one. Aberrant expression of
      MHC class II genes is associated with autoimmunity, tumour growth and failure to
      mount an immune response. RFX-B protein expression in human colorectal
      adenocarcinomas and in normal adjacent tissue was analysed in this study. Western
      blot analysis showed a suppression of nuclear RFX-B protein in the tumour tissue.
      Immunohistochemistry revealed that the RFX-B protein levels in macrophages were
      generally lower in colorectal cancerous tissue compared to adjacent non-cancerous
      tissue and that focally and not frequently tumour and normal epithelial cells
      were stained weakly for RFX-B. As the expression of MHC class II correlates with
      the intensity of the immune response system these results may support the idea
      that cancer is associated with immunodeficiency and that low levels of RFX-B in
      interstitial macrophages could partly explain this thesis.

PMID- 11836626
TI  - Lack of Bcl10 mutations in malignant cartilaginous tumors.
AB  - The Bcl10 gene was recently isolated from the breakpoint region of
      t(1;14)(p22;q32) in mucosa-associated lymphoid tissue (MALT) lymphomas. Somatic
      mutations of Bcl10 were found in not only t(1;14)-bearing MALT lymphomas, but
      also a wide range of other tumors. To clarify the actual frequency and spectrum
      of Bcl10 mutations in primary malignant chondrogenic tumors, we examined 89 cases
      of malignant chondrogenic tumors comprising 17 conventional chondrosarcomas, 33
      mesenchymal chondrosarcomas, and 39 clear cell chondrosarcomas. Polymerase chain
      reaction single-stranded conformation polymorphism and sequencing analyses were
      done. No Bcl10 mutations were found in our series of malignant chondrogenic
      tumors. While screening for mutations, we also found three polymorphisms at
      codons 8 exon 1 of the Bcl10 gene. Our results strongly suggest that somatic
      mutations of Bcl10 are extremely rare in malignant cartilaginous tumors and do
      not commonly contribute to their molecular pathogenesis.

PMID- 11836627
TI  - Molecular cloning and expression of mouse Wnt14, and structural comparison
      between mouse Wnt14-Wnt3a gene cluster and human WNT14-WNT3A gene cluster.
AB  - Glycoprotein WNTs play key roles in carcinogenesis and embryogenesis. Human WNT14
      and WNT3A genes are clustered in human chromosome 1q42 region with an interval of
      about 58 kb. Here, mouse Wnt14 was isolated to compare the structure of human
      WNT14-WNT3A gene cluster with that of mouse Wnt14-Wnt3a gene cluster. Mouse Wnt14
      showed 98.1% total-amino-acid identity with human WNT14, and 61.9% total-amino
      acid identity with human WNT14B/WNT15. Mouse Wnt14 mRNA was expressed in adult
      brain, lung, skeletal muscle, heart, and 17-day embryo. Mouse Wnt14 and Wnt3a
      genes were clustered in head-to-head manner with an interval of about 16 kb. Exon
      intron structures were well conserved between human WNT14-WNT3A gene cluster and
      mouse Wnt14-Wnt3a gene cluster. Capicua-related sequence and AK024248-related
      sequence were identified in the intergenic region of human Wnt14-Wnt3a gene
      cluster as well as in other human chromosomal loci, but not in that of mouse
      Wnt14-Wnt3a gene cluster. Capicua-related sequences were pseudogenes derived from
      Capicua gene on human chromosome 19q13. Capicua pseudogene and AK024248-related
      sequence were clustered in tail-to-tail manner with interval ranging from 2.2 to
      11.0 kb. AK024248-related sequences in several human genome draft sequences were
      truncated in the 3'-portion compared with that in the intergenic region of human
      WNT14-WNT3A gene cluster. This is the first report on structural comparison of
      WNT gene clusters in human genome and in mouse genome.

PMID- 11836628
TI  - Differential expression of Notch genes in human osteoblastic cells.
AB  - Notch receptors participate in a conserved signaling pathway that controls the
      development of diverse tissues and cell types. In the present study we
      investigated the expression of four Notch genes in primary human osteoblasts and
      in human osteoblastic osteosarcoma cell line SaOS-2 by RT-PCR. We found a strong
      constitutive expression of Notch-1 and a weak constitutive expression of Notch-2
      in both cell types. After stimulation with Dexamethasone or Vitamin D(3), two
      factors known to induce differentiation in osteogenic cells, both Notch receptors
      were downregulated, however, with a different time course. Notch-1 and Notch-2
      showed a transient induction after 2 days and a decrease after 7 days in
      osteoblasts and after 28 days in SaOS-2 cells. Notch-4 expression could only be
      detected after stimulation with Dexamethasone and Vitamin D(3). However, in
      osteoblasts a transient induction after 2 days could be detected in osteoblasts,
      whereas Notch-4 expression increased after 14 and 28 days in SaOS-2 cells. In
      contrast, Notch-3 was not expressed in human osteoblasts and SaOS-2 osteosarcoma
      cells. These data show, that Notch genes are expressed in human osteoblastic
      cells and that the expression is differentially regulated upon stimulation with
      osteogenic factors.

PMID- 11836629
TI  - Pituitary adenylate cyclase-activating polypeptide and PACAP receptor expression
      and function in the rat adrenal gland.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) is a basic 38-amino
      acid peptide, which acts through three main G protein-coupled VIP/PACAP receptor
      subtypes, called PAC1, VPAC1 and VPAC2. We have investigated the expression and
      function of PACAP and its receptors in the rat adrenal gland. Reverse
      transcription (RT)-polymerase chain reaction (PCR) and radioimmune assay (RIA)
      allowed the detection of PACAP expression as mRNA and protein exclusively in
      adrenal medulla (AM). RT-PCR and quantitative autoradiography, using
      [(125)I]PACAP and selective VIP/PACAP receptor ligands, demonstrated the
      expression of PAC1 only in AM, and VPAC1 and VPAC2 in both AM and zona
      glomerulosa (ZG), PACAP receptor expression being absent in zona
      fasciculata/reticularis (ZF/R). PACAP38 concentration-dependently increased
      aldosterone secretion from dispersed ZG cells and catecholamine secretion from AM
      tissue, the maximal effective concentration being 10(-7) M. ZF/R cells did not
      display any secretory response to PACAP38. Aldosterone response of ZG cells to
      10(-7) M PACAP38 was unaffected by the PAC1-antagonist (A) PACAP(6-38), and
      significantly decreased by the VPAC1-A [Ac-His(1),D-Phe(2),Lys(15),Arg(16)]VIP(3
      7) GRF(8-27)-NH(2). Catecholamine response of AM tissue to PACAP38 was reduced,
      but not abolished, by both PAC1-A and VPAC1-A. The VPAC2 agonist (ago) Ro25-1553
      elicited sizeable secretory responses from both ZG cells and AM tissue. PACAP38
      (10(-7) M) evoked a marked rise in cyclic-AMP (cAMP) and inositol-1,4,5
      triphosphate (IP3) production by ZG cells and AM tissue. cAMP response of ZG
      cells was lowered by VPAC1-A, and that of AM tissue by both PAC1-A and VPAC1-A.
      IP3 response of ZG cells and AM tissue was unaffected by PAC1-A and decreased by
      VPAC1-A. VPAC2-ago did not affect cAMP release, but raised IP3 production by both
      ZG cells and AM tissue. Aldosterone response of ZG cells and catecholamine
      response of AM tissue to PACAP38 (10(-7) M) were reduced by the adenylate cyclase
      (AC) and phospholipase-C (PLC) inhibitors (I) SQ-22536 and U-73122, as well as by
      the protein kinase (PK)A-I H-89 and PKC-I calphostin-C. Conversely, the secretory
      responses of both ZG and AM preparations to VPAC2-ago were annulled by PLC-I,
      lowered by PKC-I, and unaffected by either AC-I or PKA-I. Collectively, our
      findings allow us to conclude that in the rat adrenals: i) PACAP biosynthesis
      exclusively occurs in the AM; ii) ZG cells are provided with functional VPAC1 and
      VPAC2 receptors, whose activation by PACAP evokes a moderate aldosterone
      response; iii) AM cells possess all the subtypes of VIP/PACAP receptors, whose
      activation by PACAP elicits a marked catecholamine response; and iv) PAC1
      receptors are coupled to the AC-dependent cascade, VPAC1 receptors to both the AC
      and PLC-dependent cascades, and VPAC2 receptors exclusively to the PLC-dependent
      cascade.

PMID- 11836630
TI  - Sequential fluctuation pattern of serum des-gamma-carboxy prothrombin levels
      detected by high-sensitive electrochemiluminescence system as an early predictive
      marker for hepatocellular carcinoma in patients with cirrhosis.
AB  - Serum concentration levels of des-gamma-carboxy prothrombin (DCP), alpha
      fetoprotein (AFP) and Lens culinaris agglutinin-reactive fraction (AFP-L3) are
      useful tumor markers for the diagnosis of hepatocellular carcinoma (HCC).
      Recently, a novel immunoassay using the electrochemiluminescence (ECLIA) was
      developed to enable measurement of low-concentration of DCP. This study
      investigated the usefulness of high-sensitive DCP for the early diagnosis of HCC.
      The subjects consisted of 90 patients with viral cirrhosis who could be followed
      for at least 24 months from 1992 to 1997. Fifty-six of these patients developed
      HCC and 34 patients had not by 1998. We measured the serum levels of high
      sensitive DCP, AFP and %AFP-L3 every 3 months during 2 years before the detection
      of tumor in patients with HCC and during 2 years from 1995 to 97 in patients
      without HCC. Youden's index was calculated for evaluation of the ideal cut-off
      levels. The patterns of serial changes during 2 years were divided into two
      types: fluctuating type and non-fluctuating type. Cut-off levels of 40 mAU/ml for
      high-sensitive DCP (Youden's index = 0.435), 20 ng/ml for AFP (Youden's index =
      0.442) and 10% for %AFP-L3 (Youden's index = 0.364) gave the highest index for
      each marker. When these markers were combined, the combination of high-sensitive
      DCP, AFP and %AFP-L3 gave the highest accuracy (sensitivity = 82.1%, specificity
      = 82.4%, accuracy = 82.2%). Fluctuating type of high-sensitive DCP, AFP and %AFP
      L3 levels were found in 15 (17%), 29 (32%) and 11 (12%) patients, respectively.
      The rate of complication with HCC in the patients who showed the fluctuating type
      of high-sensitive DCP levels was significantly greater than that in the patients
      who showed non-fluctuating type (P<0.01). These results suggest that periodic
      measurement of serum DCP levels using ECLIA method is very useful for HCC
      screening and predicting the development of HCC.

PMID- 11836631
TI  - Molecular cloning and characterization of mouse Gipc3.
AB  - GIPC1/GIPC interacts with GTPase-activating protein RGS-GAIP, transmembrane
      protein M-SemF, receptor tyrosine kinase TrkA, integrin alpha 6A subunit, and TGF
      beta type III receptor. Kermit, a Xenopus orthologue of human GIPC1, interacts
      with Frizzled-3 (FZD3) class of WNT receptor. We have recently cloned and
      characterized human GIPC2 and GIPC3. Here, we identified mouse Gipc3 gene
      fragments by using bioinformatics, and isolated mouse Gipc3 cDNAs by using cDNA
      PCR. Mouse Gipc3 gene encoded a 297-amino-acid protein, showing 86.2% total-amino
      acid identity with human GIPC3. In addition to the central PDZ domain, GIPC
      homologous domain 1 (GH1 domain) and GH2 domain were found to be conserved among
      mouse Gipc3, Gipc1, Gipc2, and Xenopus Kermit. Mouse Gipc3 gene was found to
      consist of 6 exons, and exon-intron structure was well conserved between mouse
      Gipc3 gene and human GIPC3 gene. Mouse Gipc3 mRNA was relatively highly expressed
      in adult lung, and was also expressed in brain and testis, but was almost
      undetectable in 7-, 11-, 15, and 17-day whole embryos. This is the first report
      on molecular cloning and initial characterization of mouse Gipc3.

PMID- 11836632
TI  - Photodynamic therapy induced Fas-mediated apoptosis in human carcinoma cells.
AB  - Photodynamic therapy (PDT) is a clinical approach that utilizes light-activated
      drugs for the treatment of a variety of pathologic conditions. Human poorly
      (CNE2) and moderately differentiated (TW0-1) human nasopharyngeal carcinoma (NPC)
      cells undergo rapid apoptosis when treated with PDT sensitized with Hypocrellin A
      (HA) and Hypocrellin B (HB). It has been shown that these compounds have a strong
      photodynamic effect on tumors and viruses. The initiating events of PDT
      sensitized HA and HB-induced apoptosis are poorly defined. In the current study,
      we sought to determine whether Fas/FasL upregulation and involvement of
      mitochondrial events are an early event in HA and HB-treated PDT induced
      apoptosis. Loss of mitochondrial transmembrane potential, release of cytochrome
      c, involvement of caspases-8 and -3 and the status caspase-3 specific substrate
      PARP, were evaluated in PDT treated tumor cells. Photoactivation of HA and HB
      enhanced both CD95/CD95L expression and induced CD95-signaling dependent cell
      death in all tumor cell lines studied. CD95/ CD95L expression appeared within 2 h
      following light activation and appeared to be a primary event in PDT induced
      apoptosis. Furthermore, these results indicate that release of mitochondrial
      cytochrome c into the cytoplasm is a secondary event following the activation of
      initiator caspase-8 preceding caspase-3 activation, cleavage of PARP and DNA
      fragmentation. Cytochrome c appeared in the cytosol within 2-3 h post PDT.
      Cleavage of PARP was observed at 3-4 h following PDT and caspase-3 specific
      inhibitor DEVD-CHO and broad-spectrum caspases inhibitor z-VAD-fmk blocked
      caspase-3 activation and PARP cleavage suggesting that caspase-3 plays an
      important role in HA and HB-induced apoptosis.

PMID- 11836633
TI  - Role of estrogen receptor in the regulation of estrogen induced amino acid
      transport of System A in breast cancer and other receptor positive tumor cells.
AB  - The transport of amino acids across the plasma membrane is a process of
      fundamental physiological importance. If this process is modified by estrogens
      and if estrogen receptors play a role in this regulation, then the alteration of
      metabolic events will be of significant importance in cancer cells which have
      high estrogen receptor content because estrogens modify cellular physiology
      through transactivational effects of their cognate receptors. In the present
      study, we investigated the role of 17 beta-estradiol on the regulation of
      different amino acid transport systems, in particular, Systems A, ASC and y+ in
      estrogen receptor positive (MCF-7, T47D, H-301) and estrogen receptor negative
      (MCF-10, SKBR-3, MDA-MB-231) cell lines. The cells were treated with 17 beta
      estradiol (10 nM), ICI 182780 (1 microM), or 17 beta-estradiol plus ICI 182780.
      We discovered that 17 beta-estradiol specifically stimulates System A activity by
      2- to 4-fold in estrogen receptor positive cell lines with a maximal stimulation
      48 h after estrogen-treatment while no stimulation was observed in estrogen
      receptor negative cell lines. Estrogen-dependent activation of System A was
      inhibited by co-treatment with the antiestrogen ICI 182780. Northern blot
      analysis showed that System A mRNA levels are also increased following estrogen
      treatment, and this induction of mRNA transcript levels by estrogen can be
      inhibited by co-treatment with antiestrogen ICI 182780. The increase in System A
      transport activity following estrogen treatment was abbrogated when estrogen
      receptor positive cells were stably transfected with human antisense ER alpha
      cDNA. Kinetic analysis demonstrated that estrogen-induced stimulation results in
      a doubling of Vmax with no changes in Km. However, 17 beta-estradiol did not
      stimulate the activation of transport systems responsible for the transport of
      arginine (y+) or threonine (ASC). In summary, we have provided evidence that
      estrogen receptors play a role in the activation of System A by estrogen. This
      adaptation may have important physiological and nutritional significance on
      estrogen dependent growth of breast tumors.

PMID- 11836634
TI  - T cell dependent and independent antitumor immunity generated by the expression
      of Fas ligand on mouse lung carcinoma cells.
AB  - Interaction between Fas and Fas ligand (FasL) induces apoptotic cell death of Fas
      positive cells. Expression of FasL on tumors therefore possibly kills activated
      Fas-positive cytotoxic T cells that infiltrated into the tumors and consequently
      the tumors can evade from systemic immune responses. Previous studies however
      showed that forced expression of FasL in tumors induced neutrophil-mediated
      inflammatory reactions and accordingly produced T cell independent antitumor
      effects in the inoculated animals. We then analyzed the FasL-mediated antitumor
      responses with genetically mutated mice. Murine lung carcinoma (A11) cells
      transfected with the FasL gene (A11/FasL), which was able to kill Fas-positive B
      cells, did not form subcutaneous tumors and produced few lung spontaneous
      metastatic foci in immunocompetent mice. The mice that rejected A11/FasL cells
      developed tumor-specific protective immunity. A11/FasL cells were also rejected
      in T cell-defective nude mice and in CD18-deficient mice which showed impaired
      neutrophil functions, but not in Fas-defective (lpr/lpr) mutant mice. Antitumor
      activities on A11 cells were dependent on the number of co-injected A11/FasL
      cells but those on irrelevant B16 murine melanoma cells were not produced even
      with a large number of co-injected A11/FasL cells. In contrast to previous
      reports, the present study implies that T cells can also be effectors of FasL
      mediated antitumor responses and neutrophils are not absolutely required for the
      responses.

PMID- 11836635
TI  - c-Ets1 is a promising marker in epithelial ovarian cancer.
AB  - c-Ets1 controls the expression of some genes involved in extracellular matrix
      remodeling. To elucidate the involvement of c-Ets1 in epithelial ovarian
      carcinogenesis, we investigated the role of the proto-oncogene c-ets1 in the
      regulation of physiological processes such as cell proliferation,
      differentiation, and tumor invasion. Using fluorescent immunohistochemistry, we
      analyzed serial frozen sections for c-Ets1 protein expression in 26 patients with
      ovarian epithelial carcinoma, 10 patients with benign cystadenoma of the ovary,
      and 10 premenopausal patients with normal ovaries. We analyzed the relationship
      between the percentage of c-Ets1 stained cells in a patient and characteristics
      of the patient including histological classification, clinical stage,
      histological grade, and clinical outcome. c-Ets1 was not detected in any cases of
      benign ovarian cystadenoma. Most of the c-Ets1 proteins were found in the
      cytoplasm and some in the nucleus of epithelial ovarian cancer tissues. Moreover,
      c-Ets1 was strongly expressed in the head portion of papillary cancer tissues
      that had invaded the stroma. c-Ets1 expression was significantly associated with
      clinical stage (p<0.01), histological grade (p<0.01), and clinical outcome
      (p<0.01). Survival data were available for all patients and univariate Cox
      regression analysis showed that c-Ets1 expression was significantly associated
      with a poor prognosis (p<0.05). Our results demonstrate that c-Ets1 expression in
      epithelial ovarian cancer correlates to the malignant potential of the tumor.

PMID- 11836636
TI  - High prevalence of anticardiolipin antibodies in patients with HCV-associated
      oral lichen planus.
AB  - Hepatitis C virus (HCV) has been linked to extrahepatic manifestations such as
      oral lichen planus (OLP). In addition, anticardiolipin antibodies (aCL) and
      cryoglobulin have been demonstrated in chronic hepatitis C. The aim of this study
      was to investigate these prevalences in patients with HCV-associated OLP. The
      prospective study investigated the role of these factors in 133 subjects: 28 with
      OLP-HCV(+) (group 1), 22 with OLP-HCV(-) (group 2), 33 without OLP-HCV(+) (group
      3), and 50 healthy volunteers matched for age and sex served as control group
      (group 4). Levels of immunoglobulin G (IgG) and IgM aCL antibodies, and
      cryoglobulin in serum were evaluated by enzyme-linked immunosorbent assay. The
      prevalence of aCL in groups 1, 2, 3, and 4 were 32.1, 18, 36.3, and 8%,
      respectively. The positive rate of aCL was significantly higher in groups 1 and 3
      than that in the control group (group 1; p=0.02 vs. the control group, group 3;
      p<0.01 vs. the control group). There were no significant differences in
      cryoglobulin among the groups. The findings of the present study showed a high
      prevalence of IgG and IgM aCL in the serum of patients with HCV infectious
      diseases. A positive factor for aCL was determined by age, sex, the presence of
      OLP, and HCV infection.

PMID- 11836637
TI  - Molecular characterization of human healthy and neoplastic cerebral and renal
      tissues by in vitro (1)H NMR spectroscopy (review).
AB  - The clinical impact of (1)H NMR spectroscopy in the study of human organs, brain
      and kidney in particular, is well demonstrated. The in vitro (1)H NMR technique
      is a powerful tool for monitoring changes in intracellular metabolites of human
      normal and neoplastic cerebral and renal tissues. Healthy and tumoral tissues of
      different histologic types have been fully characterized from a biochemical
      standpoint. Molecular characterization is performed on both the aqueous and lipid
      extracts of surgically removed tissue biopsies yielding a full picture of tissue
      biochemistry. These analyses have disclosed markers of healthy brain and kidney
      and of their respective neoplastic lesions. Moreover, some biochemical features
      can differentiate neoplasms within the same histological type. In particular,
      lipidic components, like cholesteryl esters (namely oleate), detected in highest
      grade tumors, warrant further investigation. A better understanding of the
      biochemistry of diseased human tissues could open the way to new diagnostic and
      treatment strategies.

PMID- 11836638
TI  - Response of the immune system of mammary tumor-bearing rats to cyclophosphamide
      and soluble low-molecular mass tumor-associated antigens: the spleen and lymph
      nodes.
AB  - In a previous study, we showed that soluble low-molecular-mass tumor-associated
      antigens (sTAA) promote the anti-tumor effect of the anticancer drug
      cyclophosphamide (CPA) on rat mammary carcinogenesis. In this report, we analyzed
      the underlaying mechanisms. Studies were performed on the spleen and lymph nodes
      from the following groups of mammary tumor-bearing rats: i) control rats, ii)
      rats treated with sTAA, iii) rats treated with CPA, i.v.) rats treated with CPA
      and sTAA. Different zones of the spleen and lymph nodes were measured and their T
      cell content (CD4(+) and CD8(+) cells) was analyzed immunohistochemically. CPA
      decreased the size and cell content of follicles, splenic areas related to the
      production of B cells, of the marginal zone and to a lesser extent of the
      periarterial lymph sheath, and decreased the number of CD4(+) and, at a lower
      rate, of CD8(+ )T cells in the spleen. Addition of sTAA restored activity in the
      splenic zones producing these cells. Similar effects of CPA and sTAA were found
      in lymph nodes with accumulation of B lymphocytes in the primary and secondary
      follicles and of T lymphocytes, including both CD4(+) and CD8(+) cells, in the
      paracortical zone. We suggest that inhibition of the functional activity of the
      immune system is one of the main reasons for the toxic effects of
      chemotherapeutic drugs such as CPA and that the tumor-suppressive antitoxic
      effects of sTAA result from their activation of B- and T-lymphocyte production in
      this system, particularly in the spleen and lymph nodes.

PMID- 11836639
TI  - Endothelial function studies in pulmonary vascular disease: determination of
      angiotensin converting enzyme activity in humans (review).
AB  - Angiotensin converting enzyme (ACE, kininase II) is an endothelial luminal
      ectoenzyme. The majority of ACE has been found on the pulmonary capillary
      endothelium (PCE). Pulmonary capillary endothelium-bound (PCEB)-ACE has been
      extensively studied by means of indicator dilution techniques in animals and man.
      We have recently developed and applied methodologies for assaying pulmonary
      capillary endothelium-bound (PCEB) angiotensin converting enzyme (ACE) activity
      in man. This article provides a summary of our studies in human subjects
      utilizing similar methodology. Trace amounts of the specific ACE substrate, (3)H
      benzoyl-Phe-Ala-Pro ((3)H-BPAP; 40 microCi or 2 nmol), was injected as a bolus
      into the subclavian vein of patients and immediately blood was withdrawn from a
      radial arterial catheter. Plasma concentrations of surviving substrate and
      product ((3)H-benzoyl-Phe) were estimated and BPAP utilization was calculated
      during a single transpulmonary passage. To investigate the PCE in this manner we
      tested the hypothesis that PCEB-ACE is depressed in patients diagnosed with acute
      lung injury and estimated interaction of an ACE inhibitor (enalaprilat) with PCE
      in human subjects. An inverse correlation was found between the pulmonary
      endothelium-bound ACE activity (v) and the lung injury score (r=0.379; p<0.01).
      Similarly, an inverse correlation was found between the pulmonary capillary
      perfusion index (CPI) and the lung injury score (r=0.284, p<0.05). PCEB-ACE
      activity in the group of patients with mild lung injury was significantly
      different from the group of control patients (0.44 +/- 0.048 vs. 1.15 +/- 0.05;
      p<0.01). Trace amounts (1.5 microg/kg) of enalaprilat had no significant effect
      on mean arterial pressure (91 +/- 6 vs. 84 +/- 7 vs. 88 +/- 6 mmHg for T(1), T(2)
      and T(3), respectively), but significantly decreased PCEB-ACE activities. When
      normalized to pre-drug (T(1)) activity levels, enalaprilat inhibited PCEB and SE
      ACE activity at T(2) by 74 +/- 6 and 68 +/- 6%, respectively. PCEB-ACE
      measurements can be used in clinical practice for estimating PCE functions and
      can provide new insight into the physiology of the pulmonary circulation.

PMID- 11836640
TI  - [Current urogynecology].

PMID- 11836641
TI  - [Pregnancy, childbirth and the pelvic floor].
AB  - Pregnancy and vaginal delivery are responsible for the onset of genuine stress
      urinary incontinence, and pelvic floor damage. A striking dearth of prospective
      studies exists regarding the relationship of pregnancy and delivery to these
      problems. The vast majority of published data is based on analysis retrieved from
      questionnaires. Most damage of the pelvic floor obviously occurs during first
      delivery. Objective findings have demonstrated pudendal nerve damage mostly found
      after forceps delivery, increased duration of second stage of labour, third
      degree perineal tear and high birth weight. Episiotomy offers no protection
      against perineal tears and should be restricted to specified feto-maternal
      indications. Longitudinal studies are needed to assess long term consequences of
      pregnancy and child birth on both, lower urinary tract and pelvic floor function.

PMID- 11836642
TI  - [Morphologic assessment for diagnosing urogynaecologic disorders].
AB  - Morphologic assessment for diagnosing urogynecologic disorders is done as part of
      the gynecologic examination and urogenital ultrasound with the equipment
      available in the gynecologist's office. Evaluation of the pelvic floor by
      separate palpation of both sides, assessment of contractility, testing of
      speculum elevation, and ultrasound examination of voluntary motor function by
      elevation of the bladder neck during muscle contraction provide adequate
      information on the pelvic floor status for initiating pelvic floor re-education
      and/or conditioning. In assessing prolapse, differentiation of a lateral defect
      from a central defect of the anterior compartment is an important prerequisite
      for surgical decision-making in stress urinary incontinence (colposuspension
      versus TVT-plasty) and urogenital prolapse (abdominal versus vaginal access).
      Introitus or perineal ultrasound allow for reliable assessment of the topography
      of the bladder neck and will also demonstrate morphologic changes of the urethra,
      the periurethral tissue, and the bladder. - Radiographic examinations (e. g.,
      excretory urography, double-balloon urethrography, micturition
      cystourethrography, retro- and antegrade depiction of fistulae) are not part of
      the basic diagnostic work-up and should only be performed in the framework of
      specific urogynecologic assessment. These procedures are indicated for assessing
      the upper urinary tract, for confirming the diagnosis of urethral diverticulae,
      and for clarifying extraurethral urinary incontinence. - Magnetic resonance
      imaging allows for the detailed morphologic assessment of the levator ani muscle,
      the endopelvic fascia, and the urethra. However, since normal values for
      comparison have not yet been established and the examination is complicated and
      expensive, the use of MRI is still restricted to scientific investigations.

PMID- 11836643
TI  - [Pathophysiology of female incontinence].
AB  - In the last 100 years many different theories have tried to explain the symptoms
      and causes of urinary incontinence in the female. Urinary incontinence is a
      debilitating condition and not only leads to medical problems and costs, but is
      associated with embarrassment that can lead to isolation and loss of
      independence. Women with stress urinary incontinence can have both urethral
      support loss and decreased urethral function. Aging and delivery can lead to
      multiple damages which can be manifest either as loss of support with symptoms of
      prolaps or incontinence. This paper provides an overview of the functional
      anatomy of the structures responsible for controlling urinary continence under
      stress and discusses some of the theories on incontinence.

PMID- 11836644
TI  - [Possibilities and limits of the conservative treatment for urinary
      incontinence].
AB  - The conservative treatment of stress or mixed incontinence results in improvement
      or cure in about 60 % of patients. Pelvic floor muscle training without or with
      biofeedback, electrical stimulation and vaginal cones are not superior to each
      other.

PMID- 11836645
TI  - [Surgical concepts in female urinary stress incontinence].
AB  - Severe anatomical and functional defects and failure or rejection of conservative
      treatment are clear indications for surgical repair of sphincter incompetence.
      Adequate pretherapeutical diagnostic work-up should rule out other reasons for
      incontinence and additional pathology and allow adequate selection of the
      surgical technique. Prospective randomized studies as well as meta-analyses
      enable us to recognize suitable procedures; for primary surgery colposuspension
      and tension-free vaginal tapes (TVT), and in selected cases traditional slings
      can be recommended, whereas vaginal repairs, needle suspensions and the different
      injectables should not be encouraged for primary cases.

PMID- 11836646
TI  - [Pelvic organ prolapse].
AB  - Pelvic organ prolapse of the female is a common disease with age dependent
      increase in incidence. The committee for standardisation of the International
      Continence Society recently suggested to avoid classical terms such as cystocele,
      rectocele or enterocele for the description of prolapse and to replace them by
      defined landmarks. The "Pelvic Organ Prolapse Quantification" (POPQ) was
      developed and five different grades of prolapse were defined. This is a true gain
      for scientific documentation but needs some effort to be implemented in routine
      practical work. Previous normal vaginal delivery is statistically highly
      correlated with prolapse, followed by climacteric involution, constitutional
      factors, physical work, chronic bronchitis, and overweight respectively. The
      diagnosis is confirmed by clinical examination. Defects of the supportive
      structures can be precisely assessed with dynamic magnetic resonance imaging.
      Time will show whether this costly method will become part of routine diagnostic
      procedures. A patient with moderate prolapse or few complaints may be treated
      conservatively with pelvic floor training or electrotherapy. Modern pessaries are
      tried as first line therapy or for patients unwilling to undergo surgery. Local
      estrogen application should routinely be prescribed for perimenopausal patients.
      In the last decade laparoscopic techniques have been established in addition to
      standard methods of pelvic floor reconstruction. These techniques do not follow a
      new surgical strategy but realise the minimal invasive approach to established
      methods of pelvic floor reconstruction. Of note, laparoscopic fixation is very
      convenient for young women who want to preserve their uterus. Long time follow up
      is not available for most techniques.

PMID- 11836647
TI  - [Legal aspects of urogynaecology].
AB  - Lesions of the urinary tract are rare, but, typical complications of gynecologic
      surgery. Gradual loss of surgical experience results in a lack of knowledge of
      prevention and management of lesions. Pretherapeutical work-up, selection of
      adequate procedure and surgeon, recognition of atypical postoperative symptoms
      might cause mistakes in selection and organization of the physician responsible.
      The principle possibility of a laceration is a rare cause, more frequently
      disregarding of typical symptoms of complication and prolonged timing of
      additional investigations are reasons for legal implications. Recommendations of
      medical associations are of help, but, might be a burden.

PMID- 11836648
TI  - Bias in estimates of quantitative-trait-locus effect in genome scans:
      demonstration of the phenomenon and a method-of-moments procedure for reducing
      bias.
AB  - An attractive feature of variance-components methods (including the Haseman
      Elston tests) for the detection of quantitative-trait loci (QTL) is that these
      methods provide estimates of the QTL effect. However, estimates that are obtained
      by commonly used methods can be biased for several reasons. Perhaps the largest
      source of bias is the selection process. Generally, QTL effects are reported only
      at locations where statistically significant results are obtained. This
      conditional reporting can lead to a marked upward bias. In this article, we
      demonstrate this bias and show that its magnitude can be large. We then present a
      simple method-of-moments (MOM)-based procedure to obtain more-accurate estimates,
      and we demonstrate its validity via Monte Carlo simulation. Finally, limitations
      of the MOM approach are noted, and we discuss some alternative procedures that
      may also reduce bias.

PMID- 11836650
TI  - Testing for genetic linkage in families by a variance-components approach in the
      presence of genomic imprinting.
AB  - Some genes that affect development and behavior in mammals are known to be
      imprinted; and > or = 1% of all mammalian genes are imprinted. Hence,
      incorporating an imprinting parameter into linkage analysis may increase the
      power to detect linkage for these traits. Here we propose theoretical
      justifications for a recently developed model for testing of linkage, in the
      presence of genetic imprinting, between a quantitative-trait locus and a
      polymorphic marker; this is achieved in the variance-components framework. We
      also incorporate sex-specific recombination fractions into this model. We discuss
      the effects that imprinting and nonimprinting have on the power of the usual
      variance-components method and on the variance-components method that
      incorporates an imprinting parameter. We provide noncentrality parameters that
      can be used to determine the sample size necessary to attain a specified power
      for a given significance level, which is useful in the planning of a linkage
      study. Optimal strategies for a genome scan of potentially imprinted traits are
      discussed.

PMID- 11836651
TI  - Fine-scale mapping of disease loci via shattered coalescent modeling of
      genealogies.
AB  - We present a Bayesian, Markov-chain Monte Carlo method for fine-scale linkage
      disequilibrium gene mapping using high-density marker maps. The method explicitly
      models the genealogy underlying a sample of case chromosomes in the vicinity of a
      putative disease locus, in contrast with the assumption of a star-shaped tree
      made by many existing multipoint methods. Within this modeling framework, we can
      allow for missing marker information and for uncertainty about the true
      underlying genealogy and the makeup of ancestral marker haplotypes. A crucial
      advantage of our method is the incorporation of the shattered coalescent model
      for genealogies, allowing for multiple founding mutations at the disease locus
      and for sporadic cases of disease. Output from the method includes approximate
      posterior distributions of the location of the disease locus and population
      marker haplotype proportions. In addition, output from the algorithm is used to
      construct a cladogram to represent genetic heterogeneity at the disease locus,
      highlighting clusters of case chromosomes sharing the same mutation. We present
      detailed simulations to provide evidence of improvements over existing
      methodology. Furthermore, inferences about the location of the disease locus are
      shown to remain robust to modeling assumptions.

PMID- 11836649
TI  - Phylogeographic differentiation of mitochondrial DNA in Han Chinese.
AB  - To characterize the mitochondrial DNA (mtDNA) variation in Han Chinese from
      several provinces of China, we have sequenced the two hypervariable segments of
      the control region and the segment spanning nucleotide positions 10171-10659 of
      the coding region, and we have identified a number of specific coding-region
      mutations by direct sequencing or restriction-fragment-length-polymorphism tests.
      This allows us to define new haplogroups (clades of the mtDNA phylogeny) and to
      dissect the Han mtDNA pool on a phylogenetic basis, which is a prerequisite for
      any fine-grained phylogeographic analysis, the interpretation of ancient mtDNA,
      or future complete mtDNA sequencing efforts. Some of the haplogroups under study
      differ considerably in frequencies across different provinces. The southernmost
      provinces show more pronounced contrasts in their regional Han mtDNA pools than
      the central and northern provinces. These and other features of the geographical
      distribution of the mtDNA haplogroups observed in the Han Chinese make an initial
      Paleolithic colonization from south to north plausible but would suggest
      subsequent migration events in China that mainly proceeded from north to south
      and east to west. Lumping together all regional Han mtDNA pools into one fictive
      general mtDNA pool or choosing one or two regional Han populations to represent
      all Han Chinese is inappropriate for prehistoric considerations as well as for
      forensic purposes or medical disease studies.

PMID- 11836654
TI  - Leukotriene antagonists: bystanders or causes of Churg-Strauss syndrome?

PMID- 11836652
TI  - A susceptibility locus for migraine with aura, on chromosome 4q24.
AB  - Migraine is a complex neurovascular disorder with substantial evidence supporting
      a genetic contribution. Prior attempts to localize susceptibility loci for common
      forms of migraine have not produced conclusive evidence of linkage or
      association. To date, no genomewide screen for migraine has been published. We
      report results from a genomewide screen of 50 multigenerational, clinically well
      defined Finnish families showing intergenerational transmission of migraine with
      aura (MA). The families were screened using 350 polymorphic microsatellite
      markers, with an average intermarker distance of 11 cM. Significant evidence of
      linkage was found between the MA phenotype and marker D4S1647 on 4q24. Using
      parametric two-point linkage analysis and assuming a dominant mode of
      inheritance, we found for this marker a maximum LOD score of 4.20 under locus
      homogeneity (P=.000006) or locus heterogeneity (P=.000011). Multipoint parametric
      (HLOD = 4.45; P=.0000058) and nonparametric (NPL(all) = 3.43; P=.0007) analyses
      support linkage in this region. Statistically significant linkage was not
      observed in any other chromosomal region.

PMID- 11836655
TI  - Leukotriene antagonists and the Churg-Strauss syndrome.
AB  - BACKGROUND AND OBJECTIVES: Leukotriene antagonists (LTAs), or antileukotrienes,
      are a new group of anti-inflammatory drugs used for the treatment of asthma. They
      might substitute for or allow tapering of corticosteroids in asthmatic patients.
      These drugs have been associated with the development of Churg-Strauss syndrome
      (CSS), a rare form of vasculitic angiitis. It is unclear whether the development
      of CSS is a direct drug effect or an unmasking of a preexisting condition on
      withdrawal of steroids for asthma. We present a case of CSS in a patient treated
      with montelukast and review the literature to analyze the association between
      LTAs and the development of CSS. METHOD: We reviewed the literature using MEDLINE
      from February 1966 to October 2000. To the cases identified, we present an
      additional case of a patient who underwent a diagnostic lung biopsy. RESULTS:
      Twenty-two case reports of patients receiving LTAs who developed CSS were
      identified. The onset of CSS occurred 2 days to 10 months after starting
      treatment with LTAs. All patients had received inhaled or oral steroids for
      asthma. The interval between the last oral corticosteroid treatment and CSS onset
      ranged from 3 days to 8 months. CONCLUSIONS: To date, there is no compelling
      evidence that the development of CSS in asthmatic patients receiving LTAs results
      from a direct drug effect. Rather, it appears that tapering of corticosteroids in
      these patients unmasks the multiorgan manifestations of the disease. We believe
      that the use of LTAs should not be influenced by the apparent increase in the
      incidence of CSS and that these are still safe drugs for asthma.

PMID- 11836656
TI  - Rheumatic manifestations of parasitic diseases.
AB  - OBJECTIVES: To consolidate the spectrum and frequency of parasite-related
      rheumatic syndromes, which have largely been regarded as exceedingly rare by the
      general medicine, infectious disease, and rheumatology literature. METHODS: A
      MEDLINE search was performed for articles on rheumatic syndromes related to
      parasitic infections published from 1966 through December 2000. Identified
      articles included clinical and epidemiologic studies describing cases of
      rheumatic syndromes associated with verified parasitic infection. RESULTS:
      Rheumatologic syndromes, including inflammatory arthritis, inflammatory myositis,
      and vasculitis, have been described among multiple different parasite infections
      of all parasitic divisions, including Protozoa, Nematoda, and Platyhelminthes.
      Individual parasitic divisions are often associated with particular rheumatic
      syndromes, such as reactive arthritis and spondyloarthropathy, inflammatory or
      infectious myositis, and reactive or parainfectious vasculitis. CONCLUSIONS AND
      RELEVANCE: Parasitic infection may underlie the clinical presentation of some
      rheumatic conditions. Given the continued and growing number of patients at risk
      for parasitosis by virtue of their country of origin, travel habits, and an
      immunocompromised state, potential parasitosis must be considered in patients
      undergoing evaluation for rheumatic complaints.

PMID- 11836653
TI  - Association of polymorphisms in the apolipoprotein E region with susceptibility
      to and progression of multiple sclerosis.
AB  - Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous
      system, with a complex etiology that includes a strong genetic component. The
      contribution of the major histocompatibility complex (MHC) has been established
      in numerous genetic linkage and association studies. In addition to the MHC, the
      chromosome 19q13 region surrounding the apolipoprotein E (APOE) gene has shown
      consistent evidence of involvement in MS when family-based analyses were
      conducted. Furthermore, several clinical reports have suggested that the APOE-4
      allele may be associated with more-severe disease and faster progression of
      disability. To thoroughly examine the role of APOE in MS, we genotyped its
      functional alleles, as well as seven single-nucleotide polymorphisms (SNPs)
      located primarily within 13 kb of APOE, in a data set of 398 families. Using
      family-based association analysis, we found statistically significant evidence
      that an SNP haplotype near APOE is associated with MS susceptibility (P=.005). An
      analysis of disease progression in 614 patients with MS from 379 families
      indicated that APOE-4 carriers are more likely to be affected with severe disease
      (P=.03), whereas a higher proportion of APOE-2 carriers exhibit a mild disease
      course (P=.02).

PMID- 11836657
TI  - Foot involvement in systemic sclerosis: a longitudinal study of 100 patients.
AB  - OBJECTIVE: To investigate the clinical and radiologic features of foot
      involvement in systemic sclerosis (SSc). PATIENTS: One hundred patients (91
      women, 9 men; mean age, 51.9 +/- 11 years) with SSc (mean disease duration, 17.4
      +/- 10.5 years) were retrospectively studied. Seventy-four subjects had limited
      scleroderma and 26 diffuse scleroderma. METHODS: Radiologic changes of foot
      involvement were assessed at presentation (time of diagnosis) and follow-up
      ranging from 1 to 28 years (median range, 7 years) and were compared with changes
      detected in the hands of each patient at the same presentation and follow-up.
      Correlations with skin and internal organ involvement were assessed. RESULTS:
      Ninety patients had foot involvement clinically. Forty-three had it at initial
      evaluation; 47 developed it during follow-up. Median time to clinical event
      occurrence was 10 years (95% CI, 6.7-13.3) with 44% censored case probability at
      this time. The onset of clinically evident foot involvement was later in limited
      SSc than in diffuse SSc. In comparison with hands with SSc, feet with SSc had
      lower rates of necrotizing Raynaud's phenomenon and tendon friction rubs and
      decreased skin thickening scores, whereas arthralgias occurred significantly more
      often. At presentation, 37 patients had radiologic abnormalities of their feet
      compared with 69 of their hands (P <.001); the hands had a significantly higher
      prevalence of acroosteolysis (P <.001). At the end of the follow-up, 35 of 50 SSc
      patients had radiographic foot involvement compared with 50 of 51 with hand
      involvement (P <.001). A significantly higher prevalence of acroosteolysis (P
      <.001), calcinosis (P <.05), and erosions (P <.05) of the hands were detected at
      that time. CONCLUSION: This study shows that compared with hand involvement in
      SSc, foot involvement in SSc has a later onset and is relatively less frequent
      but can be disabling.

PMID- 11836658
TI  - Viral infections and antiphospholipid antibodies.
AB  - OBJECTIVE: To study the relationship between viral infections and the induction
      of antiphospholipid (aPL) antibodies. METHODS: We reviewed the medical literature
      from 1968 until 2000 using MEDLINE and the key words virus, infection,
      antiphospholipid, and anticardiolipin. RESULTS: Anticardiolipin antibodies and/or
      lupus anticoagulant were associated with a number of viral infections, including
      hepatitis C virus, human immunodeficiency virus, cytomegalovirus, varicella
      zoster, Epstein-Barr virus, adenovirus, and parvovirus B. In many instances, the
      presence of these antibodies was associated with thrombosis. CONCLUSION: The
      clinical significance of finding aPL antibodies in patients with viral infections
      remains unknown. In some patients, these antibodies may be transient and
      disappear within 2 or 3 months. In other susceptible individuals, they may
      persist and raise the question of whether infections may trigger the development
      of aPL antibodies in autoimmune diseases.

PMID- 11836659
TI  - Clinical features and predictive factors in psoriatic arthritis-related uveitis.
AB  - OBJECTIVES: To analyze the clinical features of uveitis in psoriatic arthritis
      (PsA) and to investigate the factors predicting its appearance. PATIENTS AND
      METHODS: Retrospective cohort study (1991-2000) of 71 patients diagnosed with PsA
      according to the criteria of Moll and Wright. All patients were studied according
      to a standard protocol. The group was divided into 3 articular categories: axial,
      oligoarticular, and polyarticular. Human leukocyte antigen (HLA)-Cw typing was
      performed by the polymerase chain reaction-sequence specific oligonucleotide
      probes (PCR-SSOP) method in 65 patients and in 177 healthy donors. HLA-DR typing
      was done by serologic methods in the 71 patients and in 82 healthy donors from
      the same racial and geographic origin. The HLA-B27 allele also was tested among
      the study population. All subjects with possible inflammatory ocular disease
      received a complete ophthalmologic examination at the Ophthalmology Department of
      our hospital. Only patients with uveitis were analyzed. Univariate and
      multivariate analyses were applied. RESULTS: Thirteen patients had uveitis (18%
      of this series), 4 (31%) had an insidious onset, and the remaining had acute
      onset uveitis. Five cases (39%) had bilateral-simultaneous uveitis. Ten (77%)
      presented with anterior uveitis only, 2 with anterior and posterior pole
      involvement, and only 1 case with isolated posterior pole involvement. Four
      patients needed oral corticosteroids; 2 of them also used immunosuppresive drugs.
      None of our patients developed sequelae or complications. In univariate analysis,
      uveitis was associated with inflammatory back pain (P =.02), sacroiliac pain (P
      =.001), syndesmophytes (P =.001), bilateral sacroileitis (P =.0001), HLA-DR13 (P
      =.002), and HLA-B27 (P =.026). In multivariate analysis, the predictive factors
      for uveitis were bilateral sacroileitis (OR 17, 95% CI: 3.7-76, P =.0002), HLA
      DR13 (OR 24, 95% CI: 3.78-150, P =.0056), and syndesmophytes (OR 9.7, 95% CI:
      0.97-97, P =.05). CONCLUSIONS: Insidious onset, bilaterality, posterior pole
      involvement, and chronicity are common in PsA patients with uveitis. In this
      study, extensive axial involvement (bilateral sacroileitis and syndesmophytes),
      and the HLA-DR13 antigen were the best predictors for the appearance of uveitis.

PMID- 11836660
TI  - Spontaneous pyogenic vertebral osteomyelitis in nondrug users.
AB  - OBJECTIVE: To analyze the clinical, microbiological, and radiologic features of
      patients without drug addiction suffering from spontaneous pyogenic vertebral
      osteomyelitis. METHODS: We collected all microbiologically proved cases of
      pyogenic vertebral osteomyelitis seen between January 1980 and December 1999 in a
      teaching hospital. Patients with prior spinal instrumentation or surgery and
      injection drug users were excluded. RESULTS: Sixty-four patients, with a mean age
      of 59 +/- 17 years, were identified. In 29 (45%) patients, 1 or more underlying
      medical illnesses were found. The mean duration of symptoms before hospital
      admission was 48 +/- 40 days. Neurologic impairment was present in 18 (28%)
      patients. Staphylococcus aureus and gram-negative bacilli, mainly Escherichia
      coli, were the predominant etiologic agents. Blood cultures were positive in 72%
      (46/64) of cases. The cultures of spinal specimens obtained by x-ray-guided
      biopsy were positive in 52% (11/21) of cases, and those obtained by open biopsy
      in 75% (15/20) of cases. Plain radiography showed abnormalities in all but 7
      patients. Fifty-one of 53 (96%) technetium Tc 99m diphosphonate bone scans and 40
      of 44 (91%) gallium citrate Ga 67 bone scans showed increased uptake of tracers
      in the involved area. Paraspinal and epidural extension was found on computed
      tomography and/or magnetic resonance imaging in 74% (39/53) of cases; the
      presence of an extra-vertebral extension was not associated with the development
      of neurologic findings in many patients. Two patients died in relation to the
      infectious process and 3 relapsed; functional sequelae often were found.
      CONCLUSIONS: Spontaneous pyogenic vertebral osteomyelitis in nondrug users is a
      disease that affects mainly older patients suffering underlying medical
      illnesses. S aureus and E coli are the main causative microorganisms. Positive
      blood cultures frequently aided the diagnosis. Extra-vertebral extension is
      frequent but does not indicate a worse prognosis. Although life outcome is good,
      functional sequelae are common. Diagnostic delay before admission is a concern,
      and the physician should be alert to the possibility of this condition in
      patients with back or neck pain.

PMID- 11836661
TI  - Pure red cell aplasia and lupus.
AB  - OBJECTIVE: To review the clinical and laboratory features of all reported
      patients with systemic lupus erythematosus (SLE) and pure red cell aplasia
      (PRCA). METHODS: In addition to our patient, we identified cases reported during
      the years 1966-2000 by searching the MEDLINE literature (Winspirs). Clinical and
      laboratory features were compared with those reported in large series of patients
      with SLE but without PRCA. RESULTS: Twenty-three additional cases were
      identified. In most cases, SLE was diagnosed either before or concomitantly with
      the diagnosis of PRCA. The clinical and laboratory features were not
      significantly different from those reported in large series of patients with SLE,
      except for less pleuritis and a trend toward less proteinuria, hallucinations,
      thrombopenia, and leukopenia. The natural history of PRCA and SLE was similar to
      that reported for PRCA alone. The disease responded to prednisone in the majority
      of cases, but patients frequently remained steroid dependent. CONCLUSIONS: The
      association between SLE and PRCA is rare. The clinical and laboratory features of
      SLE in such patients are similar to SLE patients without PRCA with the exception
      of a decreased frequency of pleuritis. Response to treatment of PRCA in those
      with SLE is similar to patients with PRCA but without SLE.

PMID- 11836662
TI  - Clinical challenges in osteoporosis. Case 1: screening for osteoporosis in early
      menopause.

PMID- 11836664
TI  - The pathogenesis of mesothelioma.
AB  - About 80% of malignant mesotheliomas (MM) in the Western World develop in
      individuals with higher than background exposure to asbestos. Only a fraction of
      those exposed to asbestos develop mesothelioma, indicating that additional
      factors play a role. Simian virus 40 (SV40), a DNA tumor virus that
      preferentially causes mesothelioma in hamsters, has been detected in several
      human mesotheliomas. The expression of the SV40 large tumor antigen in
      mesothelioma cells, and not in nearby stromal cells, and the capacity of
      antisense T-antigen treatment to arrest mesothelioma cell growth in vitro suggest
      that SV40 contributes to tumor development. The capacity of T-antigen to bind and
      inhibit cellular p53 and retinoblastoma (Rb)-family proteins in mesothelioma,
      together with the very high susceptibility of human mesothelial cells to SV40
      mediated transformation in vitro, supports a causative role of SV40 in the
      pathogenesis of mesothelioma. Asbestos appears to increase SV40-mediated
      transformation of human mesothelial cells in vitro, suggesting that asbestos and
      SV40 may be cocarcinogens. p53 mutations are rarely found in mesothelioma; p16,
      p14ARF, and NF2 mutations/losses are frequent. Recent studies revealed the
      existence of a genetic factor that predisposes affected individuals to
      mesothelioma in the villages of Karain and Tuzkoy, in Anatolia, Turkey. Erionite,
      a type of zeolite, may be a cofactor in these same villages, where 50% of deaths
      are caused by mesothelioma. Mesothelioma appears to have a complex etiology in
      which environmental carcinogens (asbestos and erionite), ionizing radiation,
      viruses, and genetic factors act alone or in concert to cause malignancy.

PMID- 11836665
TI  - The epidemiology of mesothelioma.
AB  - It has been more than 40 years since occupational crocidolite exposure in South
      African miners was found to be associated with development of malignant
      mesothelial tumors 30 to 40 years later. Similar cases were not seen in the
      amosite and chrysotile miners. Since then, epidemiological and toxicological
      knowledge have increased enormously, but mortality continues to rise steeply (5%
      to 10% per year) in most industrialized countries. Even with widespread asbestos
      abatement efforts, this increase is likely to continue in Western Europe and the
      United State well into the next century, at least until 2020. Unregulated use of
      asbestos in less industrialized countries may cause the epidemic to continue
      throughout the next century in those regions. Asbestos abatement seems to be
      successful as evidenced by a decline in the proportion of patients with
      peritoneal tumors, which are the most common malignancies in heavily exposed
      individuals. Whereas in the 1960s peritoneal tumors comprised up to 30% of the
      total, in recent years the proportion has fallen to about 10%, This changing
      ratio could also be due to the steady increase in pleural tumors. The difficulty
      in formulating the connection as to the etiology of mesothelioma resulted from an
      unforeseeable difference in the carcinogenicity of various asbestos and mineral
      fiber types and was compounded by the very long latency of the disease.
      Unfortunately, the use of a single term, "asbestos," to describe at least five
      fibrous silicate minerals, each with unique physical, chemical, and biological
      properties and not infrequently and naturally admixed, severely hampered
      scientific investigation into the occupational health risks. The field became
      confused and filled with debate. At the heart of the fiber type controversy lies
      a fundamentally differing view of the importance of biopersistence of various
      asbestos fibers in carcinogenesis. This review will deal with the epidemiology of
      mesothelioma with particular attention to the studies that elucidate the impact
      of various asbestos fiber types on the etiology of the disease.

PMID- 11836666
TI  - The role of imaging in malignant pleural mesothelioma.
AB  - Imaging plays an essential role in the diagnosis, staging, and follow-up of
      patients with malignant pleural mesothelioma (MPM). The diagnosis is often
      suggested by a unilateral pleural mass with a moderate to large pleural effusion
      seen on chest radiographs, but computerized tomography (CT) is the most
      frequently used technique for evaluation of the lungs in patients with MPM. CT
      not only suggests pulmonary metastases typically manifested as nodules or masses,
      but also can demonstrate underlying lung disease often caused by prior asbestos
      exposure. Magnetic resonance (MR) imaging may be helpful in selected patients
      with potentially resectable disease to further examine the local extent of tumor.
      Imaging with positron emission tomography (PET) using the radionuclide imaging
      agent (18)F fluoro-deoxyglucose (FDG) takes advantage of a basic property of
      tumor cells, increased glucose metabolism to identify malignant lesions. PET
      provides not only anatomic information, especially regarding mediastinal node
      metastasis, but also biochemical information about the lesion. These imaging
      modalities help triage patients to the most appropriate diagnostic and treatment
      options. Following patients after therapy usually relies on chest radiographs,
      although CT can more accurately describe response to therapy. This review will
      focus on radiologic evaluation in diagnosing, staging, and follow-up patients
      with MPM.

PMID- 11836667
TI  - Prognostic factors in mesothelioma.
AB  - Prognostic factors in oncology may help physicians give their patients a
      prognosis for their disease and thus allow them to make plans for the future.
      These factors also assist in the selection of patients more likely to benefit
      from intensive treatments, especially in the context of clinical trials. Recently
      it has become clear that prognostic factors may have an additional benefit: they
      may provide insight into the biology of the cancer being studied and lead to
      improved understanding of the molecular pathogenesis. For malignant mesothelioma,
      the prognostic scoring systems of the Cancer and Leukemia Group B (CALGB) and
      European Organization for Research and Treatment of Cancer (EORTC) are the most
      useful of those currently available. These systems rate performance status, age,
      histological subtype, weight loss, and hematological parameters as the best
      prognostic factors for malignant mesothelioma. In the future, biological markers
      may provide additional information on mesothelioma and will help in
      prognostication.

PMID- 11836668
TI  - Multimodality treatment of diffuse malignant pleural mesothelioma.
AB  - Diffuse malignant pleural mesothelioma (DMPM) is a challenging disease in all of
      its aspects, from presentation and diagnosis to staging and treatment. Single
      modality therapy was the initial approach to this disease. It generally has not
      been effective in changing the natural history of DMPM. As a result,
      multimodality regimens involving surgery with radiation, chemotherapy, or
      immunotherapy delivered regionally or systemically have been evaluated.
      Randomized controlled studies comparing various strategies are lacking and, thus,
      the debate continues regarding the effectiveness of different treatment
      approaches.

PMID- 11836669
TI  - Diagnosis and treatment of peritoneal mesothelioma: The Washington Cancer
      Institute experience.
AB  - Peritoneal mesothelioma is a rare disease, but increasing in frequency. The
      incidence is approximately one per 1,000,000 and about one fifth to one third of
      all mesotheliomas are peritoneal. Because of its unusual nature, the disease has
      not been clearly defined either in terms of its natural history, diagnosis, or
      management. This article reviews a single institution's experience with 51
      patients prospectively treated over the past decade with increasingly aggressive
      local/regional protocols. Peritoneal mesothelioma patients generally present with
      two types of symptoms and signs; those with abdominal pain, usually localized and
      related to a dominant tumor mass with little or no ascites and those without
      abdominal pain, but with ascites and abdominal distention. Pathologically, a
      positive immunostain for calretinin has markedly increased the accuracy of
      diagnosis. Prognosis as determined by clinical presentation, the completeness of
      cytoreduction, and gender (females survive longer than males) appears to be
      improved by the use of intraperitoneal chemotherapy. Over the past decade, the
      management of these patients has evolved similarly to ovarian cancer treatment
      and now involves cytoreductive surgery, heated intraoperative intraperitoneal
      chemotherapy (HIIC) with cisplatin and doxorubicin, and early postoperative
      intraperitoneal paclitaxel. These perioperative treatments are followed by
      adjuvant intraperitoneal paclitaxel and second-look cytoreduction. Prolonged
      disease-free survival and reduced adverse symptoms with the current management
      strategy are documented by a high complete response rate as assessed by a
      negative second-look. This multimodality treatment approach with cytoreductive
      surgery and intraperitoneal chemotherapy has resulted in a median survival of 50
      to 60 months. Peritoneal mesothelioma is an orphan disease that is treatable with
      expectations for "potential" cure in a small number of patients if diagnosed and
      treated early with definitive local/regional treatments. A prolonged high quality
      of life is possible in the majority of patients.

PMID- 11836670
TI  - Chemotherapy for malignant mesothelioma: from doxorubicin to vinorelbine.
AB  - It has been a challenge to find effective chemotherapeutic treatments for
      malignant mesothelioma. Over the last several decades numerous single-drug and
      combination regimens have been examined, but no standard treatment with
      chemotherapy alone has emerged. Possible explanations for this lack of success
      are the heterogeneity between the different subclasses of mesothelioma and the
      difficulties experienced in determining responses on computed tomographic (CT)
      scan. This review will present the results of most chemotherapy trials. An
      attempt is also been made to overcome the problem of identifying the overall
      response rate by presenting the median survival time. Other types of response
      evaluation and guidelines for patient selection are warranted to properly compare
      chemotherapeutic treatments.

PMID- 11836671
TI  - The role of gemcitabine in the treatment of malignant mesothelioma.
AB  - Gemcitabine is broadly active in a variety of solid tumors, including malignant
      mesothelioma. In vitro, gemcitabine demonstrates activity against mesothelioma
      cell lines. The role of single-agent gemcitabine in patients with mesothelioma is
      unclear, since three phase II trials treated a total of 60 patients and achieved
      response rates of 0%, 7%, and 31%. The combination of gemcitabine and cisplatin
      is synergistic against mesothelioma cell lines in vitro. Gemcitabine in
      combination with cisplatin or carboplatin shows definite activity in phase II
      trials. The trial by Byrne and colleagues that demonstrated a response rate of
      48% established the combination of gemcitabine plus cisplatin as a standard
      therapy for this disease in the United States. Subsequent multicenter trials have
      achieved lower response rates of 26% and 16% for this combination. Gemcitabine
      plus carboplatin also has activity. Future roles for gemcitabine in malignant
      mesothelioma patients include incorporating a gemcitabine/platinum regimen for
      neoadjuvant or adjuvant therapy, combining it with other cytotoxic chemotherapy
      agents such as pemetrexed or vinorelbine, or adding novel cytostatic agents such
      as the vascular endothelial growth factor (VEGF) inhibitor, bevacizumab, to the
      gemcitabine and platinating agent combination.

PMID- 11836672
TI  - The emerging role of antifolates in the treatment of malignant pleural
      mesothelioma.
AB  - Clinicians have long regarded malignant pleural mesothelioma as a chemoresistant
      neoplasm and as a result no standard chemotherapy regimen has emerged.
      Antifolates such as methotrexate are among the most active compounds in
      mesothelioma, albeit based only on phase II data. Recently two antifolate-based
      combinations with apparently higher efficacy than older regimens have emerged:
      the pemetrexed/cisplatin regimen and the raltitrexed/oxaliplatin regimen. In two
      phase I trials with pemetrexed combined with either cisplatin or carboplatin
      responses occurred in five of 11 and nine of 29 patients, respectively. In a
      phase I trial of raltitrexed/oxaliplatin, six of 17 patients (35%) with
      mesothelioma achieved a partial response. In a phase II trial of
      raltitrexed/oxaliplatin, 14 objective responses were confirmed in 72 patients
      (25%) with malignant pleural mesothelioma. Indeed, responses were seen in
      cisplatin-refractory patients. Based on the promising results from these
      combination trials, two large phase III studies have begun. The first study was a
      multicenter, multinational trial sponsored by Eli Lilly and Company, which
      randomized more than 430 patients with malignant pleural mesothelioma to
      cisplatin with or without pemetrexed. That trial completed enrollment in February
      2001 and is the largest trial ever conducted in mesothelioma. The second trial is
      being conducted by the European Organization for the Research and Treatment of
      Cancer (EORTC) and compares cisplatin with or without raltitrexed with planned
      accrual of 240 patients. In both trials, survival is the main endpoint. These
      trials will help to define the role of these new antifolates in malignant pleural
      mesothelioma.

PMID- 11836674
TI  - Multicenter randomized controlled trial of the management of unresectable
      malignant mesothelioma proposed by the British Thoracic Society and the British
      Medical Research Council.
AB  - Malignant mesothelioma is almost invariably fatal. The incidence of the disease
      is rising rapidly in many countries, and there is no generally accepted standard
      treatment for patients with unresectable disease. According to current British
      Thoracic Society (BTS) guidelines, patients should be treated with active symptom
      control (ASC), involving (1) regular follow-up in a specialist clinic; (2)
      structured assessments of physical, psychological and social problems with
      appropriate action; (3) rapid involvement of additional specialists; and (4)
      parallel nursing support. Although many nonrandomized studies have reported tumor
      responses to anticancer chemotherapy, few have studied palliation and it is not
      known whether chemotherapy prolongs survival or provides clinically worthwhile
      palliation with acceptable toxicity when given in addition to ASC. We therefore
      plan to conduct a multicenter randomized controlled trial comparing (1) ASC
      alone, (2) ASC plus mitomycin vinblastine and cisplatin (MVP), and (3) ASC plus
      vinorelbine (N; Navelbine, Pierre Fabre Oncology, Winchester, UK). We chose these
      chemotherapy regimens because they have been shown in nonrandomized studies to
      provide good symptom control as recorded by patients. The outcome measures are
      overall survival, palliation of symptoms, performance status, analgesic usage,
      toxicity, quality of life, tumor response, and recurrence/progression-free
      survival. In a preliminary feasibility study, we are assessing the acceptability
      of the trial design to patients and the suitability of two standard quality-of
      life instruments in mesothelioma. Data will help us to decide the final details
      of the large multicenter trial.

PMID- 11836673
TI  - New approaches for mesothelioma: biologics, vaccines, gene therapy, and other
      novel agents.
AB  - Although malignant mesothelioma is not a classically immunogenic cancer, there is
      abundant evidence for immune recognition. The relative ease of obtaining tumor
      tissue makes mesothelioma ideal for studying surrogate biomarkers such as
      lymphocytic infiltration or expression of transduced genes. There is evidence
      that malignant mesothelioma patients as well as asbestos-exposed persons without
      mesothelioma have impaired immune responsiveness. Substantial progress has been
      made in animal models using several biological and immunological techniques, but
      clinical application has been problematic. Systems studied have included lysis by
      interleukin-2 (IL-2)-activated lymphokine-activated killer (LAK) cells, tumor
      necrosis factor-alpha (TNF-alpha), a p16-expressing adenovirus vector, suicide
      gene therapy using the herpes simplex virus-tyrosine kinase (HSV-tk) followed by
      ganciclovir, and immunomodulatory gene therapy with IL-2, IL-4, interferon-gamma
      (IFN-gamma), IFN-alpha, TNF-alpha, granulocyte-macrophage colony-stimulating
      factor (GM-CSF), IL-6, and IL-1beta transfected into tumors. Vaccinia virus has
      been studied as a vector for cytokine gene transfer. Suicide gene therapy has
      been combined with a tumor vaccine. The University of Western Australia is
      initiating a pilot study of autologous vaccination in malignant mesothelioma.
      Novel agents under study include the angiogenesis inhibitors SU5416, bevacizumab,
      and thalidomide. ZD1839, an orally administered, highly selective inhibitor of
      the epidermal growth factor receptor (EGFR) tyrosine kinase, is being tested in a
      phase II trial. Since platelet-derived growth factor (PDGF) is thought to be an
      autocrine growth factor for mesothelioma STI-571 (Gleevec; Novartis, Basel,
      Switzerland), a highly selective inhibitor of the PDGF receptor tyrosine kinase,
      is being tested in a phase II trial. The development of more active cytotoxic
      combinations in this disease should facilitate further studies of
      chemoimmunotherapy. It seems likely that no single treatment modality will be
      effective by itself.

PMID- 11836675
TI  - [Genetic variations in plasminogen activator inhibitor-1 gene and beta fibrinogen
      gene associated with glomerular microthrombosis in lupus nephritis and the gene
      dosage effect].
AB  - OBJECTIVE: To explore the relationship of plasminogen activator inhibitor-1 (PAI
      1) gene -675 4G/5G and beta fibrinogen gene -455 G/A variations to glomerular
      microthrombosis(T) in lupus nephritis(LN). METHODS: One hundred and one patients
      with biopsy proven LN were divided into two groups according to the presence or
      absence of glomerular microthrombus, i.e. group LN+T(n=46) and group LN-T(n=55).
      The genotypes of PAI-1 gene and beta fibrinogen gene were profiled by polymerase
      chain reaction-sequence length polymorphism (PCR-SLP) and polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP) respectively.
      Clinical baseline data at the time of renal biopsy were collected. Normal
      controls consisted of 128 unrelated healthy adults. The etiologic fractions (EF)
      were calculated for estimating the contribution of risk genotypes of the two
      candidate genes to an increase in susceptibility to glomerular microthrombosis in
      LN patients. RESULTS: Both the 4G/4G genotype and the 4G allele of PAI-1 gene
      occurred more frequently in group LN+T (47.83% and 0.685) than in group LN-T
      (23.64% and 0.507)(P<0.05) and normal controls (28.13% and 0.570) (P<0.05). The
      PAI-1 4G/4G genotype was significantly associated with microthrombosis (OR=2.96,
      95%CI:1.26-6.92). Besides, the prevalence of the genotypes carrying the A allele
      of beta fibrinogen gene, i.e. G/A and A/A, as well as the prevalence of the A
      allele per se, was increased in group LN+T (47.83% and 0.261) versus group LN-T
      (27.27% and 0.145)(P<0.05). LN patients carrying the A allele had a high risk of
      glomerular thrombosis(OR=2.44, 95%CI:0.98-5.59). In addition, the presence of the
      PAI-1 4G/4G genotype together with the A allele of the beta fibrinogen gene was
      found to be a greater risk factor (OR=4.5, 95%CI: 1.34-15.12) for glomerular
      thrombosis in LN than the 4G/4G genotype or the A allele alone. The pooled EF
      (45.98%) for the risk genotypes of both PAI-1 gene and beta fibrinogen gene was
      also higher than that for the risk genotypes of either gene (31.67% and 28.23%).
      CONCLUSION: The above findings indicated that genetic variations in PAI-1 and
      beta fibrinogen loci might represent risk factors for glomerular microthrombosis
      in LN. They may have synergetic impact and present gene dosage effect on the
      susceptibility to this pathological subphenotype.

PMID- 11836676
TI  - [Linkage disequilibrium study of microsatellite markers on chromosome 6 and
      schizophrenia].
AB  - OBJECTIVE: To explore the relationship between the microsatellite markers on
      chromosome 6 and schizophrenia by linkage disequilibrium analysis. METHODS:
      Twenty-eight microsatellite markers on chromosome 6 were evaluated in 115
      affected-sib-pair and trios families. Linkage disequilibrium analysis was
      conducted according to diagnostic categories, Positive and Negative Syndrome
      Scale (PANSS) and other clinical data by XDT and MAPMAKER/SIBS software system.
      RESULTS: Significant P value (P<0.005) was found in all the four diagnostic
      categories. Only the locus of D6S1960 showed positive P value (P<0.05) in all the
      subgroups divided by PANSS scale and the age of onset. CONCLUSION: The area
      around D6S1960 in short arm of chromosome 6 may contain susceptibility gene of
      schizophrenia.

PMID- 11836677
TI  - [p53 gene codon 72 polymorphism and susceptibility to esophageal squamous cell
      carcinoma in a Chinese population].
AB  - OBJECTIVE: To investigate the relationship between p53 codon 72 polymorphism and
      susceptibility to esophageal squamous cell carcinoma in China. METHODS: The p53
      genotypes were determined by polymerase chain reaction-restriction fragment
      length polymorphism among 204 healthy controls and 91 patients with esophageal
      squamous cell carcinoma (ESCC). RESULTS: There was no significant difference
      between patients and controls with respect to allele frequency for the p53 Pro
      allele (0.480 versus 0.588, P=0.11); however, the Pro/Pro genotype of p53 among
      cases (39.6%) was significantly (P<0.05) more frequent than that among controls
      (21.1%). Subjects homozygous for the p53 Pro allele had a more than 2-fold
      increased risk of developing ESCC (OR=2.18; 95%CI=1.10-4.35, adjusted for age,
      sex, and smoking), whereas the Arg/Pro genotype was not associated with elevated
      risk of the cancer (adjusted OR=0.84; 95%CI=0.42-1.68). No interaction between
      smoking and Pro/Pro genotype was observed for risk of ESCC. CONCLUSION: The p53
      codon 72 polymorphism may play a role in susceptibility to esophageal
      carcinogenesis.

PMID- 11836678
TI  - [Genescan analysis of non-small cell lung cancer in the long arm of chromosome
      6].
AB  - OBJECTIVE: To investigate if there are microsatellite loci in the long arm of
      chromosome 6 that have close relationship with non-small cell lung cancer.
      METHODS: Multiple PCR approach was used to analyze the 18 loci in the long arm of
      chromosome 6. The PCR products were analyzed in PAGE, and then the
      electrophoresis maps were analyzed with Gene Scan(TM) and Genotyper(TM). RESULTS:
      There were different frequencies of loss of heterozygosity (LOH) in different
      loci (varying from 3.85% to 38.45%). The total frequency of LOH in 41 gastric
      cancers was 58.5%(24/41). Eight loci with the LOH frequency higher than 20% were
      mainly located in 2 regions: 6q24 and 6q27. The accurate location is 6q24-6q25.3
      [D6S1699(35%), D6S409(23.33%), D6S441(33.33%)] and 6q26-27 [D6S1550(38.45%),
      D6S264(20%), D6S1585(25%), D6S446(33.33%), D6S281(30.77%)]. CONCLUSION: There may
      be tumor suppressor genes located in the region of 6q24 and 6q27, which have
      close relationship with non-small cell lung cancer.

PMID- 11836679
TI  - [Study on the construction of standard D12S391 allelic ladder and its genetic
      polymorphism in six populations].
AB  - OBJECTIVE: To resolve the problem of the accuracy and standardization of short
      tandem repeat-polymerase chain reaction (STR-PCR) typing in forensic practice,
      the authors have designed a new method of producing standard D12S391 allelic
      ladder. METHODS: Nine different PCR amplified D12S391 allelic fragments were
      isolated from the gel, eluted into the distilled water and re-amplified by PCR.
      The purified allelic fragments were then blunt-end subcloned individually into
      the pUC plasmid vectors and transfected into competent E.coli DH5 alpha(TM)
      cells. The sequencing results confirmed that the size and the structure of the
      inserts were correct. The recombinant plasmids DNA with 9 inserts were then used
      as templates for PCR re-amplification to generate D12S391 standard ladder.
      RESULTS: With the ladder, the authors studied the genetic polymorphisms of
      D12S391 locus in six populations (German, Japanese and Chinese south-western Han,
      northern Han, Weiwu'er and Hui populations), and the respective primary data in
      the six populations were obtained. D12S391 locus showed high polymorphism in all
      six populations, and its exclusion power and discrimination power are 0.609-0.786
      and 0.940-0.952 respectively. CONCLUSION: The results demonstrate that the
      standard ladder generated via this method is excellent, and D12S391 locus is
      robust for genetic research and forensic application.

PMID- 11836680
TI  - [Linkage analysis of X-linked nuclear protein gene in Smith-Fineman-Myers
      syndrome].
AB  - OBJECTIVE: To determine the linkage between Smith-Fineman-Myers syndrome (SFMS)
      and X-linked nuclear protein(XNP) locus. METHODS: Polymerase chain reaction and
      denaturing polyacrylamide gel electrophoresis were used to genotype two
      polymorphic short tandem repeats within XNP gene. RESULTS: One of the two short
      tandem repeats was informative in SFMS family from Shandong, China. Recombination
      between SFMS locus and XNP gene was observed in the SFMS family. CONCLUSION: XNP
      gene is not associated with the disease in the SFMS family from Shandong, China.
      SFMS exhibits locus heterogeneity at molecular level.

PMID- 11836681
TI  - [The full sequence of intron 51 of dystrophin gene and its characteristic of
      sequence].
AB  - OBJECTIVE: To finish the work of sequencing the full sequence of intron 51 of
      dystrophin gene and understand its characteristic of sequence. METHODS: The whole
      intron 51 was sequenced by primer walking. The sequencing results were analyzed
      by repeat sequences, matrix attachment region (MAR) and topoisomerase II cleavage
      sites. The residue sequences, after removal of the repetitive sequences, were
      subjected to the analysis of CpG islands, promoter, open reading frame (ORF) and
      unidentified low copy repeat sequence. RESULTS: The acquired intron 51 sequence
      was composed of 38725 bp. Repetitive sequences constituted 37.53% of total intron
      sequence. The overall G+C content of intron 51 was 36.34%. There are four
      potential MARs in intron 51. Three of them are clustered in the 12 kb region near
      exon 51. Numerous ORFs were found on both strands, but no homologues proteins
      were found in Genbank CDS transcriptional peptide, PDB, SwissProt, PIR and PRF
      databases. CONCLUSION: The expansion of intron 7 over the last 120 million years
      was mainly the result of L1 insertion into intron 7, and not all of repetitive
      sequences are associated with chromosomal rearrangement. No sequence of
      functional significance was found in intron 51. The results suggest that the
      cluster of MARs may be associated with the instability of intron 51.

PMID- 11836682
TI  - [Homozygous deletion of p16 and p15 genes in laryngeal squamous cell carcinoma].
AB  - OBJECTIVE: To assess the relationship of homozygous deletion status of p16
      (MTS1/INK4a/CDKN2A), p15(MTS2/INK4b/CDKN2B) genes and laryngeal squamous cell
      carcinoma(LSCC) progression. METHODS: DNA was extracted from fresh tumors.
      Homozygous deletion of p16 exon 2(p16E2) in 80 cases of LSCC and p15 exon
      2(p15E2) in 67 cases of LSCC were detected by the polymerase chain reaction
      technique. RESULTS: The p16E2 deletion rate in 80 cases was 12.5%(10/80); the
      p15E2 deletion rate in 67 cases was 11.94%(8/67); the p16E2 and p15E2 codeletion
      rate in 67 cases was 5.97%(4/67). CONCLUSION: Homozygous deletion of p16E2 and
      p15E2 is related with LSCC oncogenesis, and it may play a role to some extent in
      LSCC malignant progression.

PMID- 11836683
TI  - [Polymorphisms of four microsatellite markers tightly linked with polycystic
      kidney disease 2 gene in Chinese].
AB  - OBJECTIVE: To investigate the polymorphisms of four microsatellites, D4S1534,
      D4S1563, D4S423 and D4S414, which are tightly linked to polycystic kidney disease
      2 (PKD2) gene, and hence to provide a basis for studying the heterogeneity of
      adult polycystic kidney disease (APKD). METHODS: An analysis on the DNA of some
      unrelated Chinese people was performed using polymerase chain reaction (PCR),
      polyacrylamide gel electrophoresis (PAGE) and silver staining. RESULTS: In
      Chinese Hans, there are 11 alleles of D4S1534, and their sizes are 142-162 bp  14
      alleles of D4S1563, 205-235 bp  17 alleles of D4S423, 103-135 bp; and 15 alleles
      of D4S414, 236-264 bp. The polymorphism information contents of the four
      microsatellites are 0.872, 0.844, 0.921 and 0.871 respectively. CONCLUSION: In
      the Chinese Han people studied above, the four microsatellite markers that have
      many alleles are highly polymorphic genetic markers and may serve as the data of
      population genetics, suggesting that all four microsatellites could be used in
      studies on heterogeneity of APKD, linkage analysis of APKD and forensic personal
      identification.

PMID- 11836684
TI  - [Analysis on point mutation of the CDKN2/p16 gene in lung cancer].
AB  - OBJECTIVE: To study the status of CDKN2/p16 gene point mutation in lung cancer.
      METHODS: Polymerase chain reaction-single strand conformation polymorphism (PCR
      SSCP) and sequencing were used to detect the point mutation of CDKN2/p16 gene
      exon 2 in 89 cases of lung cancer. RESULTS: In 69 cases of the lung cancer
      without deletion of CDKN2/p16 gene exon 2, 16 cases were found to have suspicious
      abnormality of CDKN2/p16 gene exon 2 by PCR-SSCP, and in these 16 cases, 9 were
      found to harbor point mutations of CDKN2/p16 gene exon 2 by automated sequencing
      analysis. CONCLUSION: The point mutation is one of the mechanisms for CDKN2/p16
      gene inactivation, but it is not the chief mechanism. The inactivation of
      CDKN2/p16 gene aroused by point mutation plays a role to some extent in the
      genesis and progression of lung cancer.

PMID- 11836685
TI  - [Association between the genetic polymorphisms of beta2-adrenergic receptor gene
      and the asthma susceptibility and clinical phenotypes in a Chinese population].
AB  - OBJECTIVE: To determine whether genetic polymorphisms of beta2-adrenergic
      receptor gene affect asthma susceptibility and play a role in disease regulation.
      METHODS: One hundred and sixty-six unrelated childhood asthma cases and 32
      families with 192 samples were studied. The polymorphisms at amino acid positions
      16, 27, 164 and nucleic acid residue 523 were genotyped by polymerase chain
      reaction-restriction endonuclease digestion. RESULTS: The amino acid 164 Thr/Ile
      variant was seen only in the heterozygote form, and it occurred with a frequency
      of 3% which is similar to the published results among Caucasians. There were
      significant differences in the allele frequencies of the other 3 polymorphisms
      between Chinese and the published results among Caucasians (P<0.001). No
      polymorphism was found to be associated with total serum IgE, the number of
      positive prick skin test and FEV1. No significant association was noted between
      either the arginine-glycine 16 or the glutamine-glutamate 27 polymorphisms and
      the airway responsiveness to beta2-agonists in childhood asthma cases.
      CONCLUSION: In this study population, the authors were unable to confirm that the
      polymorphism of beta2-adrenergic receptor gene is a crucial factor of the
      susceptibility to asthma and a major genetic determinant of different clinical
      status.

PMID- 11836686
TI  - [A preliminary study of pentanucleotide repeat polymorphism of apolipoprotein(a)
      gene in coronary atherosclerotic heart disease].
AB  - OBJECTIVE: This study inquired into the relationship between a pentanucleotide
      repeats(PNR) polymorphism of the apolipoprotein(a)[apo(a)] gene and coronary
      atherosclerotic heart disease(CHD) in Chinese Han nationality. METHODS: PNR
      polymorphism of the apo(a) gene from 165 cases of CHD and 153 normal individuals
      were analyzed by polymerase chain reaction(PCR)-denature polyacrylamide gel
      electrophoresis-silver stain. RESULTS: The frequencies of (TTTTA)(5/8) genotype
      (0.188) and (TTTTA)(5) allele (0.115) in CHD group were remarkably higher than
      those in control group (0.039, 0.026)(P<0.01, P<0.05). CONCLUSION: These findings
      indicate that the PNR polymorphism of apo(a) is associated with the
      susceptibility to CHD, which may be involved in the development of CHD.

PMID- 11836688
TI  - [Cytochrome P450 2C19 gene polymorphism in four Chinese nationality populations].
AB  - OBJECTIVE: To study the cytochrome P450 2C19(CYP2C19) gene polymorphism in 4
      Chinese nationality populations. METHODS: The genotypes of the unrelated Miao,
      Buyi, Tu and Dulong subjects were analyzed by polymerase chain reaction and
      restriction fragment length polymorphism (RFLP). RESULTS: CYP2C19*2 allele
      frequencies were 0.291, 0.329, 0.315 and 0.349 in Miao, Buyi, Tu and Dulong
      population, respectively. The four populations were consistent with Hardy
      Weinberg expectations (P>0.05). CONCLUSION: The frequencies of CYP2C19*2 were in
      agreement with those of other published data on Asian, but were different from
      those data on European and African.

PMID- 11836687
TI  - [Comparative study of HLA-DQA1 and HLA-DRB1 allele in patients with endometriosis
      and adenomyosis].
AB  - OBJECTIVE: To make a comparative study of HLA-DQA1 and HLA-DRB1 allele
      frequencies in the cases of endometriosis and adeonmyosis. METHODS: The allelic
      types of HLA-DQA1 and HLA-DRB1 were detected by polymerase chain reaction
      sequence specific primers (PCR-SSP) technique in 51 cases of endometriosis, 45
      cases of adenomyosis, and 44 normal individuals as the control. RESULTS: The
      frequencies of HLA-DQA1*0401(7.8%, 10.0%) were significantly increased in the
      endometriosis group and the adenomyosis group (Pc=0.03, Pc=0.01), and the
      frequencies of HLA-DQA1*0301(8.8%, 5.6%) were significantly decreased in these
      two groups (Pc=0.00, Pc=0.00).There was no significant difference between the
      frequencies of HLA-DQA1 and HLA-DRB1 of endometriosis and adenomyosis.
      CONCLUSION: The results indicate that HLA-DQA1*0301 and *0401 alleles are
      associated with both endometriosis and adenomyosis, and there is perhaps common
      mechanism involved in both endometriosis and adenomyosis based on HLA-DQA1 and
      HLA-DRB1 allele frequencies.

PMID- 11836689
TI  - [Genetic polymorphism of D16S539, D7S820 and D13S317 loci in the Kazak ethnic
      population].
AB  - OBJECTIVE: To analyze the genetic polymorphism of D16S539, D7S820 and D13S317 in
      Chinese Kazak ethnic population from Xinjiang. METHODS: One hundred and two
      unrelated individuals and a sample of families (n=42) were investigated by
      multiplex amplification, 6% denaturing PAGE and silver staining. And, the
      obtained allele frequencies were compared with those of other populations.
      RESULTS: Eight, seven, eight alleles were observed at the 3 STR loci respectively
      and the genotypes distributions were in accordance with Hardy-Weinberg
      equilibrium. The expected heterozygosities for these loci were 0.9439, 0.9356 and
      0.9304; the calculated polymorphism formation content (PIC) was 0.9905; the
      discrimination power (DP), 0.9998; the paternity exclusion (PE), 0.9572. In
      addition, significant difference was found in comparison with other populations,
      and in the sample of families (n=42) no new mutations could be found. CONCLUSION:
      The multiplex examination of 3 STR loci can be used in forensic identification
      and population genetics research.

PMID- 11836691
TI  - [The relationship of p53 gene mutation to cell differentiation and metastasis of
      laryngeal squamous cell carcinoma].
AB  - OBJECTIVE: To inquire about the relationship of p53 gene mutation to the
      histopathological findings and clinical manifestation in cases of laryngeal
      squamous cell carcinoma(LSCC). METHODS: The fresh samples from 60 cases of LSCC
      were examined. Polymerase chain reaction and silver staining-single strand
      conformation polymorphism (PCR-SSCP) and DNA direct sequencing were used to
      detect the mutation of p53 gene in exons 5-8. RESULTS: The mutation rates were
      69.2% and 85.3% in patients at clinical stage I-II and stage III-IV respectively
      (P>0.05). In the well-, moderately- and poorly-differentiated cell of LSCC, the
      mutation rates were 52.9%, 83.3% and 94.7% respectively (P<0.05). The p53 gene
      mutation rate of LSCC patients with neck lymph-node metastasis was 96.4%, whereas
      that of patients without neck lymph-node metastasis was 62.5% (P<0.05). Twenty
      samples showed positive results in SSCP; 19 samples showed deletion and mutation
      in codons 125-292 by DNA direct sequencing. CONCLUSION: The mutation of p53 gene
      in exons 5-8 was closely related to cell differentiation and the neck lymph-node
      metastasis of LSCC, but it was not related to the clinical stages of the LSCC
      cases.

PMID- 11836690
TI  - [Correlation between HLA-DQA1 allele and anaphylactoid purpura in juvenile Hans
      residing in Inner Mongolia].
AB  - OBJECTIVE: To analyze the genetic susceptibility of HLA-DQA1 allele to
      anaphylactoid purpura(AP)and its association with the clinical features in
      juvenile Hans residing in Inner Mongolia. METHODS: Seventy children with AP and
      ninety normal controls of Hans in Inner Mongolia were subjected to HLA-DQA1
      genotyping with the use of polymerase chain reaction-sequence specific primer
      (PCR-SSP) technique. RESULTS: (1) The gene frequency of HLA-DQA1*0301 of AP group
      (33.4%) was significantly higher than that (10.6%) of control group (chi
      square=21.899, P<0.01). On the other hand, the gene frequencies of HLA-DQA1*0302
      were 6.7% and 19% in the AP group and the control group respectively; a
      significant difference between them was seen (chi square=9.786, P<0.01); (2)The
      gene frequencies of both DQA1*0301 and DQA1*0302 in the cutaneous purpura simplex
      cases and the controls were not significantly different (P>0.05). The gene
      frequencies of DQA1*0301 of the cutaneous purpura cases associated with
      gastrointestinal, joint and renal impairment were 26.7%, 28.5% and 29.3%
      respectively, which were higher than that of the control group (10.6%); the
      differences were statistically significant (P<0.01, 0.01, 0.01; respectively).
      The gene frequencies of HLA-DQA1*0302(3.9%, 5.7% and 9.6%) for the cutaneous
      purpura cases associated with gastrointestinal, joint and renal impairment were
      significantly lower than that (19%) of the controls except renal
      impairment(P<0.01, 0.01, respectively). CONCLUSION: The allele of HLA-DQA1*0301
      was probably a susceptible gene while HLA-DQA1*0302 was the protective one in AP
      of the children who were Han inhabitants in Inner Mongolia. The results of this
      study also revealed that patients with the allele of HLA-DQA1*0301 tended to
      involve gastrointestinal, joint and renal impairment.

PMID- 11836692
TI  - [Screening for mitochondrial DNA mutation in two pedigrees with nonsyndromic
      inherited sensorineural hearing loss].
AB  - OBJECTIVE: To investigate the genetic mechanism of maternal nonsyndromic
      inherited sensorineural hearing loss(SNHL), to identify the incidence of the
      7445(G) mutation in such pedigrees and sporadic patients with SNHL, and to
      provide the theoretical evidence for the diagnosis of this disease. METHODS:
      Blood samples were obtained from 2 pedigrees and 14 sporadic patients with SNHL.
      DNA was extracted from the isolated leukocytes. The mitochondrial DNA (mtDNA)
      fragments were amplified by PCR. The 1555(G), 3243(G) and 7445(G) mutation was
      detected by Alw 26 I, Apa I and Xba I restriction endonuclease digestion
      respectively. The sequence of 12S rRNA, tRNA(Leu(UUR)) and tRNA(Ser(UCN)) was
      examined. RESULTS: Restriction endonuclease digestion analysis showed that 12
      individuals from 2 pedigrees carried homoplasmic 7445(G) mutation, which was of
      maternal inheritance. Six individuals from 2 pedigrees and 14 sporadic patients
      did not have 7445(G) mutation. All individuals did not have 1555(G) and 3243(G)
      mutation. The sequence analysis further showed that none of them carried
      homoplasmic 1555(G) and 3243(G) mutation, 12 individuals had (nt)7445 A--> G
      substitution in tRNA(Ser(UCN)) gene. CONCLUSION: The incidence of 7445(G)
      mutation in such pedigrees is higher than that in sporadic patients. Screening
      for mtDNA 7445(G) mutation combined with 1555(G) examination is of much value to
      clinical use.

PMID- 11836693
TI  - [An improved PCR-based megaprimer method for site-directed mutagenesis].
AB  - OBJECTIVE: To establish an improved, simple and convenient megaprimer PCR method
      for site-directed mutagenesis(SDM). METHODS: This protocol is based on the design
      of two different plasmid DNA templates. Template 1 lacks the binding site for
      reverse flanking primer, and template 2 lacks the binding site for forward
      flanking primer. This modification avoids amplification of full-length wild-type
      sequences while two templates, the forward and reverse flanking primers exist
      simultaneously in one reaction tube. A megaprimer is synthesized in the first PCR
      reaction using template 1, forward primer and mutagenic primer. The megaprimer
      that needn't the cumbersome gel purification step is directly added to the second
      PCR reaction system. The second PCR reaction(PCR 2) containing two stages is
      performed using template 2, megaprimer, forward and reverse flanking primer.
      During the first stage of PCR 2, the megaprimer is extended to form the full
      length mutation product. In the second stage of PCR 2, the extended megaprimer
      containing SDM residues is subsequently amplified with the two flanking primers.
      All of the final PCR products contained the desired mutation. RESULTS: Fifteen
      types of rare beta-thalassemia mutations in Chinese were obtained using this
      method. Each of these modified fragments was separately cloned into the pGEM-T
      vector and sequenced. The desired mutations involved in mutagenesis amplicons
      were identified in all clones. CONCLUSION: This improved PCR-based megaprimer
      method for site-directed mutagenesis is rapid, simple and highly efficient, and
      the success rate of mutagenesis could reach 100%. Furthermore, this method is
      suitable for routine application in molecular cloning.

PMID- 11836694
TI  - [Fluorescence in situ hybridization study on the chromosome 17 aneuploidy of
      human oocytes failing to fertilize in vitro].
AB  - OBJECTIVE: Compare two methods of preparing human unfertilized oocytes interphase
      nucleus and analyze the relationship between the different in vitro
      fertilization(IVF) indications, ovarian stimulation protocols, women's age and
      frequency of chromosome 17 aneuploidy. METHODS: Tarkowski's air-drying method(3:1
      methanol:acetic acid) and Coonen's 0.1% Tween 20/0.01 mol/L HCl method were used
      to fix human unfertilized oocytes interphase nucleus, and telomeric probe of
      17qter was used by standard fluorescence in situ hybridization(FISH) procedures
      to confirm chromosome 17qter aneuploidy. RESULTS: Of 36 human unfertilized
      oocytes, 24 were haploid (66.7%), 7 were disomic (19.44%), 5 were trisomic
      (13.89%). The overall frequency of aneuploidy was 33.3%. There were no
      differences between the protocols characterized by different maternal age, IVF
      indication, ovarian stimulation. CONCLUSION: Tarkowski's air dry method is as
      good as the method of Coonen's, but the latter method can avoid the smell
      pollution of the methanol and acetic acid, and it is easy to operate. The
      chromosome 17 aneuploidy is one of the factors to cause in vitro fertilization
      failure of human oocytes.

PMID- 11836695
TI  - [Advances in preimplantation genetic diagnosis for chromosomal translocation
      carrier].
AB  - Chromosomal translocation is a kind of common chromosomal abnormality. The
      carriers with chromosomal translocation could have more chance of normal
      pregnancy with the help of fluorescence in situ hybridization(FISH). This is a
      review aimed at analyzing the meiosis types of the translocation chromosome. The
      strategy of preimplantation genetic diagnosis for the carriers with chromosomal
      translocation is also discussed.

PMID- 11836696
TI  - Atypical glandular cells of undetermined significance in conventional
      cervical/vaginal smears and thin-layer preparations.
AB  - BACKGROUND: Biopsy follow-up of a cervical/vaginal smear interpretation of
      atypical glandular cells of undetermined significance (AGUS) most often reveals
      either a benign reactive process or a squamous cervical intraepithelial neoplasia
      (CIN) rather than a glandular one. The ThinPrep Papanicolaou test (TP) has been
      shown to increase diagnostic sensitivity for CIN. To the authors' knowledge there
      are few studies examining its effectiveness in diagnosing uterine glandular
      lesions, either endocervical or endometrial. The authors compared outcomes after
      AGUS interpreted in TP specimens and conventional smear preparations (CPs).
      METHODS: Follow-up was sought in all cases that were interpreted as AGUS during a
      3-year period in which practice groups converted from CPs to TPs. A tissue
      diagnosis of adenocarcinoma in situ, CIN of Grade 2 or 3, or invasive carcinoma
      was considered to be a positive follow-up result. Either a benign biopsy finding
      with a subsequent benign cytologic result or two consecutive benign cytologic
      results were considered to be negative follow-up results. RESULTS: AGUS was
      reported in 116 of 75,002 TPs (0.15%) and 151 of 79,322 CPs (0.19%). Follow-up
      information was available in 91 (78%) and 130 (86%) cases, respectively. The
      predictive value of AGUS for a positive follow-up result was 22% in the TP group
      and 15% in the CP group. An AGUS interpretation with a positive follow-up result
      was found in 0.027% of all cases using TPs and in 0.025% of all cases using CPs.
      CONCLUSIONS: The use of TPs may increase the diagnostic specificity of AGUS for a
      high-grade precursor lesion or carcinoma.

PMID- 11836697
TI  - Adenocarcinoma of the cervix.
AB  - BACKGROUND: The current study examines 1) the sensitivity of detection of
      invasive adenocarcinoma of the cervix in a routine cervical screening service,
      and 2) the frequency in smears of cytologic criteria previously found to be
      useful in diagnosis. METHODS: Data on women with diagnoses of adenocarcinoma of
      the cervix accessioned at the Western Australian Cervical Cytology Registry
      during the period 1993-1998 were examined, where smears had been reported by
      Western Diagnostic Pathology within three years of the biopsy diagnosis. Smears
      and biopsy material were reviewed. RESULTS: Thirty-six smears from 24 women were
      reviewed. Of those, 58.3% had been reported as a possible or definite high grade
      epithelial abnormality (HGEA). On review it was thought that this could be
      improved to 77.8%. The screening or diagnostic error was thus 19.4% and the
      sampling error 22.2%. The likelihood of an individual woman receiving a report of
      a possible or definite HGEA in the three years before biopsy was 83.3%. In
      retrospect this could have been improved to 91.7%. Heavy bloodstaining with
      abundant abnormal glandular epithelium (14 smears) and small three-dimensional or
      papillary clusters (16 smears) were the most frequent clues to invasion. Tumor
      necrosis/diathesis was present in eight smears, but easily seen in only four,
      while marked nuclear pleomorphism and macronucleoli were seen in three and one
      smears respectively. In cases with a discrepancy between the initial and the
      review findings, very small amounts of abnormal material (three smears), a
      resemblance to endometrial cells (one smear), and an unusual appearance of folded
      monolayered sheets (three smears) contributed to the difficulty of diagnosis.
      CONCLUSIONS: There were significant sampling and screening/diagnostic errors
      (22.2% and 19.4%, respectively). Screening and diagnostic errors could perhaps be
      reduced by a greater awareness of the range of cytologic changes, but these may
      be subtle. Heavy bloodstaining with abundant abnormal glandular material may be a
      useful clue to invasive, rather than in situ, adenocarcinoma, even in the absence
      of tumor diathesis or fully malignant nuclear criteria.

PMID- 11836698
TI  - Use of human papillomavirus DNA testing to compare equivocal cervical cytologic
      interpretations in the United States, Scandinavia, and the United Kingdom.
AB  - BACKGROUND: Human papillomavirus (HPV) DNA testing may be useful in clarifying
      equivocal cervical cytologic interpretations. One application might be to
      standardize the meaning of equivocal interpretations from laboratories in various
      regions. Because international differences may be particularly marked,
      international comparisons of emerging data will require clear translations of
      "equivocal" and similar terms. METHODS: To perform a three-country comparison,
      the authors selected a morphologically diverse set of 188 conventional
      Papanicolaou tests initially classified as "squamous atypia" from a study of more
      than 20,000 women in Portland, Oregon (1989-1990). Previously, five U.S. expert
      cytopathologists independently interpreted the slides with screening
      cytotechnologists' marks in place. For this comparison, one British and two
      Scandinavian reviewers involved in HPV research reviewed the slides after
      original marks had been removed. The authors compared all eight reviewers'
      classifications of negative, equivocal, or abnormal in a series of pairwise
      comparisons using the kappa statistic. They then compared cytologic
      interpretations with HPV DNA testing. RESULTS: Oncogenic HPV DNA detection was
      significantly associated with increasingly abnormal interpretations for each
      reader. The British reader tended to rate tests as more abnormal than the
      American pathologists did, whereas the Scandinavians tended to rate tests as more
      normal. Reference to the HPV DNA standard clarified the tendency of readers to
      render systematically more or less severe interpretations. For example, the
      Scandinavian cytologists discounted subtle (often HPV-associated) changes in
      favor of cytologic certainty, making HPV triage of equivocal tests less
      applicable there. CONCLUSIONS: International research on cytopathology,
      particularly on the possible uses of HPV DNA testing, will require calibration of
      local cytologic definitions.

PMID- 11836699
TI  - Cytology of desmoplastic small round cell tumor.
AB  - BACKGROUND: Desmoplastic small round cell tumor (DSRCT) is a high-grade malignant
      tumor that has a predilection for adolescent males and usually affects the
      abdominal cavity. The cytology literature regarding DSRCT, including aspirates
      and ascitic fluid, is limited. To the authors' knowledge, findings in ThinPrep
      slides have not been described previously. METHODS: Seven cytologic specimens
      from five patients with histologically confirmed DSRCT were reviewed. Five
      specimens were fine-needle aspiration biopsies (FNABs), (liver, flank soft
      tissue, abdomen, and two resected colons [pericolic]) and two specimens were
      ascitic fluid. Cytologic features were studied in ThinPrep slides and direct
      smears, which included hematoxylin and eosin, Papanicolaou, and Quik-Dip stains.
      RESULTS: All specimens showed moderate to high cellularity. The tumor cells were
      arranged singly and in clusters. The cells demonstrated high nuclear/cytoplasmic
      ratios, granular chromatin reminiscent of small cell carcinoma, usually
      inconspicuous nucleoli, smooth to irregular nuclear membranes, and frequent
      nuclear molding. The cytoplasm was scant to moderate, pale blue, and occasionally
      vacuolated. Pseudorosettes were observed in six specimens. One ThinPrep slide and
      the direct smears contained cells with perinuclear, cytoplasmic densities.
      Stromal fragments were present in the direct smears but were uncommon in
      ThinPrep. Three specimens were diagnosed as being consistent with DSRCT. Two
      specimens were diagnosed as malignant small cell tumor. Molecular studies
      performed on histologic material in four cases confirmed the presence of the
      diagnostic translocation, t(11;22)(p13;q12). CONCLUSIONS: DSRCT may be diagnosed
      accurately in cytology specimens. Characteristic cytologic features include
      granular chromatin, smooth to irregular nuclear membranes, nuclear molding,
      cytoplasmic vacuoles, pseudorosettes, and metachromatic stroma. Cytoplasmic
      densities may be observed in direct smears and ThinPrep slides.

PMID- 11836700
TI  - Cytology of myoepithelial carcinoma of the salivary gland.
AB  - BACKGROUND: Myoepithelial carcinoma, also know as malignant myoepithelioma, is
      rare in the salivary gland, and its cytologic features have rarely been reported.
      DESIGN: Four cases of myoepithelial carcinoma with cytology were retrieved from
      the archives of the Pathology Departments of two academic institutes. In three
      cases, the specimens were obtained by fine needle aspiration biopsy (FNA); the
      remaining case was a bench aspiration performed on the surgically resected
      specimen at the time of intra-operative consultation. The cytologic features were
      reviewed and correlated with the histology. RESULTS: The four patients with
      myoepithelial carcinoma (two men and two women) ranged in age from 48 to 64
      years. Three cases arose from the parotid gland, and the remaining case was a
      recurrent tumor in the minor salivary glands of the hard palate. The aspirates of
      two cases consisted of predominantly spindle cells, one predominantly
      epithelioid/plasmacytoid cells, and one with a mixture of both spindle and
      epithelioid/plasmacytoid cells. Cellular pleomorphism was noted in two cases and
      mitotic figures in three cases. Two cases were cytologically diagnosed as
      malignant spindle cell neoplasm, not otherwise specified. The FNA of the
      recurrent tumor was diagnosed as consistent with the previous malignancy. The
      remaining case was interpreted as a pleomorphic adenoma with atypia. CONCLUSIONS:
      The cytologic features of myoepithelial carcinoma are diverse and may lack overt
      features of malignancy. Pathologists should be aware of this entity when
      evaluating cytologic specimen of salivary gland mass.

PMID- 11836701
TI  - Fine needle aspiration cytology of hepatobiliary cystadenoma with mesenchymal
      stroma.
AB  - BACKGROUND: Hepatobiliary cystadenomas (HBCs) with mesenchymal stroma (MS) are
      rare cystic neoplasms occurring exclusively in women. Hepatobiliary cystadenoma
      consists of a mucin-producing cyst lining epithelium underlined by a dense MS
      cell layer. In the current study, the authors review the fine needle aspiration
      cytology of HBC with MS and identify characteristic cytologic features that
      suggest such an uncommon neoplasm on aspirates. METHODS: A search of the
      histopathology files at the University of Texas Medical Branch at Galveston for
      the interval of January 1992 through December 2000 yielded four cases of HBC
      having both cytologic and histologic specimens. The cytologic features of the
      aspirates were reviewed and correlated with the clinical history, radiologic
      findings, and the histopathology of the excised specimens. RESULTS: All four
      patients were middle-aged women (mean age, 48.5 years) who presented with
      epigastric pain radiating to the back, due to large cystic lesions in the right
      liver lobe (three patients) or the left liver lobe (one patient). Aspiration
      cytology revealed chronic inflammatory exudate in all cases, along with
      occasional aggregates of bland, cuboidal-columnar epithelial cells (in three
      cases), which rarely arranged in papillary clusters. No significant atypia,
      evidence of malignancy, or MS cells were identified on the aspirates. HBC with MS
      was confirmed histologically on the excised specimens in all cases. CONCLUSIONS:
      By ensuring adequate sampling and correlating with consistent clinical and
      radiologic findings, a diagnosis of HBC or cystic hepatobiliary neoplasm can be
      suggested on the basis of aspiration cytology.

PMID- 11836702
TI  - Thyroid transcription factor-1 is highly sensitive and specific in
      differentiating metastatic pulmonary from extrapulmonary adenocarcinoma in
      effusion fluid cytology specimens.
AB  - BACKGROUND: Thyroid transcription factor-1 (TTF-1) is a homeodomain-containing
      transcription factor selectively expressed in thyroid, lung and diencephalon. It
      has been shown to label pulmonary adenocarcinoma, thyroid tumors, and small cell
      carcinoma (pulmonary and extrapulmonary) with relatively high sensitivity and
      specificity. The usefulness of this immunostain in cytology specimens has not
      been thoroughly discussed in the literature. METHODS: The authors evaluated 36
      effusion cytology cases (17 pleural effusion, 18 ascitic fluid, and 1 pericardial
      effusion) diagnosed as metastatic adenocarcinoma and with cell blocks prepared
      from the file of Pamela Youde Nethersole Eastern Hospital, Hong Kong, during a
      three-year period from 1998 to early 2001. The clinical, radiologic, cytologic,
      and histologic (if any) findings were reviewed. A provisional diagnosis of the
      primary site was deduced for each of the 36 cases by clinical, radiologic, and/or
      histologic correlation. Immunohistochemical study was performed on the cell block
      sections of the effusion cytology specimens using mouse monoclonal antibody
      against TTF-1, after microwave heat-antigen retrieval. The results were
      correlated with the primary origin of the metastatic adenocarcinoma. RESULTS:
      Among the 17 cases of metastatic pulmonary adenocarcinoma, 15 cases showed
      nuclear staining for TTF-1 in most of the tumor cells (sensitivity, 88.2%). None
      of the 19 cases of metastatic extrapulmonary adenocarcinoma expressed TTF-1
      (specificity, 100%). CONCLUSIONS: The current study validates TTF-1 as a highly
      sensitive and specific immunomarker for distinguishing between metastatic
      pulmonary and extrapulmonary adenocarcinoma in effusion cytology specimens, which
      are known to be associated with intrinsic artifact due to less than ideal
      cellular preservation.

PMID- 11836703
TI  - Diagnostic utility of the HepPar1 antibody to differentiate hepatocellular
      carcinoma from metastatic carcinoma in fine-needle aspiration samples.
AB  - BACKGROUND: The cytopathologic distinction between hepatocellular carcinoma (HCC)
      and metastatic carcinoma (MC) in the liver can be problematic, especially in
      patients with poorly differentiated HCC, in whom a trabecular pattern, bile
      production, and Mallory bodies may not be apparent on small fine-needle
      aspiration (FNA) samples. HepPar1 (OCH1E5) is a monoclonal antibody specifically
      developed to react with hepatocytes. It rarely reacts with bile duct and
      nonparenchymal liver cells. METHODS: FNA samples (cell blocks) from 75 liver
      tumors were selected. These included 50 moderate to poorly differentiated HCC
      cases, 5 cholangiocarcinoma (CC) cases, and 20 MC cases (4 from the breast, 4
      from the stomach, 4 from the pancreas, and 8 from the colon). Immunohistochemical
      staining for HepPar1 was performed to differentiate HCC from MC. RESULTS: The
      HepPar1 antibody was positive in 50 of 50 HCC cases (100%). The positivity was
      cytoplasmic, diffuse, and granular. All 5 cases of CC were found to be negative
      (0%). Although focal positivity within tumor cells was noted in one case,
      cytologically these were entrapped normal hepatocytes between the tumor cells. In
      addition, 3 of 20 MC cases (15%) also were positive for HepPar1. All three cases
      originated from gastric primary tumors and exhibited diffuse, granular
      cytoplasmic staining. CONCLUSIONS: The results of the current study demonstrate
      that HepPar1 is an effective marker with which to differentiate between HCC and
      CC and/or MC. HepPar1 was found to demonstrate 100% positivity in HCC cases,
      compared with 0% and 15% positivity, respectively, in CC and MC cases. In
      addition, HepPar1 is extremely helpful in limited tissue samples from FNA.
      Although 15% of the MC cases in the current study were found to be positive, with
      the help of clinical correlation and other immunohistochemical stains a definite
      diagnosis could be rendered. Potential pitfalls include residual benign
      hepatocyte staining within a non-HCC malignancy, as was observed in one of the CC
      cases in the current study.

PMID- 11836704
TI  - Diagnostic utility of Glut-1 and CA 15-3 in discriminating adenocarcinoma from
      hepatocellular carcinoma in liver tumors biopsied by fine-needle aspiration.
AB  - BACKGROUND: Diagnosing liver tumors can be difficult in the setting of a poorly
      differentiated tumor or tumors with no known prior malignancy. Frequently, alpha
      fetoprotein, carcinoembryonic antigen, factor VIII, and mucicarmine have been
      employed to distinguish hepatocellular carcinoma (HCC) from adenocarcinoma.
      However, these stains have their limitations. CA 15-3 and Glut-1 are expressed in
      a variety of carcinomas. To the authors' knowledge, their expression in HCC has
      not been studied extensively. The authors examined the clinical utility of CA 15
      3 and Glut-1 in the setting of fine-needle aspiration biopsy samples from the
      liver. METHODS: Thirty-five cases of HCC and 59 cases of tumors metastatic to the
      liver were studied. These cases previously were studied with the hepatocyte
      paraffin-1 antibody. Each case was stained with CA 15-3 and Glut-1 using the
      avidin-biotin complex method. Each case was evaluated in a blinded fashion for
      membranous staining that was stronger than cytoplasmic or background staining.
      The diagnoses were unblinded and staining patterns were compared. RESULTS: CA 15
      3 stained 43 of 59 metastatic carcinoma samples and 3 of 35 HCC samples. Glut-1
      stained 34 of 59 metastases and 2 of 35 HCCs. Together, the 2 immunostains
      stained 51 of 59 metastases and 5 of 35 HCCs. Diagnostic accuracy was improved by
      adding hepatocyte paraffin-1 to the staining panel. CONCLUSIONS: CA 15-3 and Glut
      1, especially in conjunction with hepatocyte paraffin-1, appear to be helpful in
      discriminating HCC from other carcinomas.

PMID- 11836705
TI  - Introduction: a second generation of resilience research.

PMID- 11836706
TI  - Understanding family resilience.
AB  - Families, as social systems, can be considered "resilient" in ways that parallel
      descriptions of individual resilience. In this article, the conceptualization of
      family-level outcomes as a prerequisite for assessing family competence, and
      hence their resilience, is presented relative to the unique functions that
      families perform for their members and for society. The risk and protective
      processes that give rise to resilience in families are discussed in terms of
      family stress and coping theory, with a particular emphasis on the family's
      subjective appraisal of their sources of stress and their ability to manage them.
      An effort is made to distinguish two perspectives on resilience: exposure to
      significant risk as a prerequisite for being considered resilient versus
      promotion of strengths for all families in which life in general is viewed as
      risky. Implications for practitioners and policy makers in working with families
      to promote their resilience are discussed.

PMID- 11836707
TI  - Heroes in the nursery: three case studies in resilience.
AB  - This article examines the therapeutic work in three cases (child, adolescent,
      adult) to study the impact of a supportive and nurturing parent early in life
      upon the development of resilience. The close analysis of the clinical material
      of each client's personal narrative is the primary source. The metaphor of
      "heroes in the nursery" is posited as a vehicle for enhancing understandings of
      the development of resilience. Each case provides additive meaning to recent
      studies that elevate the importance of the memories of parents to the development
      of resilient responses of children later in life. Each case reveals specific
      dimensions of the impact of heroes in the nursery which extend our understandings
      of resiliency in children and adolescents as a proactive response to stress,
      trauma, and loss.

PMID- 11836708
TI  - Abused child to nonabusive parent: resilience and conceptual change.
AB  - Individuals who were abused as children and have spontaneously, without
      intervention, been able to change their cognitive and behavioral patterns such
      that they do not abuse their own children represent a heretofore untapped source
      of information and understanding about the processes of conceptual change and
      resilience. This pilot study investigates the nature of this conceptual change as
      an exemplar of resilience. Birth order, gender, locus of control, and coping
      behaviors emerged as areas needing further study. Additionally, the belief on the
      part of the abusing parents that abuse was not wrong needs further investigation
      as a possible precursor to this particular context for conceptual change.

PMID- 11836709
TI  - Protective factors related to antisocial behavior trajectories.
AB  - A group of 115 fifth- and sixth-grade Latino students were surveyed at the
      beginning and the end of the school year before their transition to middle or
      junior-high school about their engagement in antisocial behaviors and about
      individual, social, and behavioral protective factors. The best predictors of
      decreases in antisocial behavior for these students, above and beyond variance
      for initial ratings and gender, were student perceptions of social support,
      parent supervision, and classroom participation. The importance of keeping
      students engaged in school academic work as a protection against antisocial
      behavior is emphasized as well as the need to help students gain skills necessary
      to access support for this academic work.

PMID- 11836710
TI  - Resilience elements in students with learning disabilities.
AB  - Seven elements of resilience are identified in college students who have learning
      disabilities. These elements become the bases for approaches to assisting
      children in constructing resilience when facing such difficulties.

PMID- 11836711
TI  - From theory to practice: school leaders' perspectives on resiliency.
AB  - Resiliency describes the ability of children to overcome adversity and become
      successful adults. School-based programs, strategies, or policies designed to
      enhance resiliency are relatively new. School administrators (n = 10) who had
      attended an informational meeting about a community-wide resiliency initiative
      were interviewed about their understanding of resiliency and their present and
      future plans to implement resiliency initiatives in their schools. Interviewees
      provided various definitions of resiliency, ranging from a relatively narrow
      focus on individual characteristics to a broad focus on various environmental
      factors. Only those administrators who uniformly held the belief that resiliency
      was an environmental phenomenon that could be promoted in a school setting
      decided to participate in the community-wide initiative. However, the concept of
      resiliency has captured the imagination of these school administrators and is
      seen as a relevant organizing point for designing school programs and school
      environments.

PMID- 11836712
TI  - The metatheory of resilience and resiliency.
AB  - Resiliency and resilience theory is presented as three waves of resiliency
      inquiry. The identification of resilient qualities was the first wave
      characterized through phenomenological identification of developmental assets and
      protective factors. The second wave described resilience as a disruptive and
      reintegrative process for accessing resilient qualities. The third wave
      exemplified the postmodern and multidisciplinary view of resilience, which is the
      force that drives a person to grow through adversity and disruptions. Application
      of resilience using an educational and practical framework provides a means for
      connecting with and nurturing a client's resilience. Practical paradigms of
      resiliency that empower client control and choice are suggested.

PMID- 11836713
TI  - In vitro maturation of primordial follicles after cryopreservation of human
      ovarian tissue: problems remain.

PMID- 11836714
TI  - Pilot trial of tumor-specific peptide vaccination and continuous infusion
      interleukin-2 in patients with recurrent Ewing sarcoma and alveolar
      rhabdomyosarcoma: an inter-institute NIH study.
AB  - BACKGROUND: Patients with recurrent Ewing sarcoma and alveolar rhabdomyosarcoma
      have poor prognoses and limited therapeutic options. We have investigated the use
      of peptide pulsed vaccination in an attempt to immunologically target the
      breakpoint region of tumor specific fusion proteins expressed in these tumors.
      PROCEDURE: Sixteen patients with recurrent, translocation positive, Ewing
      sarcoma, and alveolar rhabdomyosarcoma underwent apheresis for collection of
      peripheral blood mononuclear cells. Following countercurrent centrifugal
      elutriation, an apheresis product comprised predominantly of monocytes but
      containing small numbers of circulating immature dendritic cells was pulsed with
      peptides derived from the breakpoint region of the fusion proteins. Vaccines were
      administered intravenously concomitant with continuous intravenous rhIL-2 at 9 x
      10(6) IU/m(2)/day. RESULTS: Toxicity was limited to IL-2 related effects and was
      generally mild. Following vaccination, all patients showed progressive disease,
      most in a rapid fashion following the first vaccine. One patient showed evidence
      of an immunologic response and another showed a mixed clinical response. Patients
      enrolled on this tumor vaccine trial showed significant immunosuppression and
      large bulky tumors. CONCLUSIONS: Peptide vaccination as administered in this
      trial did not alter the dismal clinical outcome for patients with recurrent
      pediatric sarcomas. Future trials of tumor vaccines in this population should
      target patient populations with improved immune competence and smaller tumor
      burdens. Furthermore, optimization of the antigen presenting cell populations may
      be important for inducing immune responses to peptide antigens.

PMID- 11836715
TI  - Body composition of long-term survivors of acute lymphoblastic leukaemia.
AB  - BACKGROUND: Long-term quality of life is of growing importance in children
      previously treated for malignancy. Obesity defined indirectly from indices of
      height and weight, has been described in long-term survivors of acute
      lymphoblastic leukaemia (ALL) and hypothesised to be a consequence of previous
      cranial irradiation. PROCEDURE: In this study, measures of whole and regional
      body composition using skinfold and dual energy X-ray absorptiometry (DEXA)
      measurements have been made in 35 long-term survivors of ALL who had received
      cranial irradiation and chemotherapy. To assess the influence of cranial
      irradiation, results were compared with those obtained in 21 children treated for
      other malignancies, who received chemotherapy alone and with 31 healthy sibling
      controls. RESULTS: Girls treated for ALL were significantly fatter than those
      treated for other malignancies or healthy control siblings whether measured by
      skinfold thickness (median (range) 37.4% (17.9-41.3) vs. 24.6% (19.1-35.0) and
      28.8% (19.6-43.1), respectively, P<0.01) or DEXA (33.5% (20.5-42.8) vs. 25.5%
      (16.5-31.0) and 24.5% (18.8-53.6), respectively, P<0.01). Boys treated for ALL
      were not significantly fatter than boys in the other two groups. Measures of
      whole body percent fat derived from DEXA were persistently less than those
      derived from skinfold measurements with a mean (95% CI) difference of 2.4% (1.7
      3.1, P<0.001) for all groups combined. In ALL survivors, using regression
      equations for skinfold thicknesses derived from controls with DEXA as the 'gold
      standard' method, fat mass was significantly overestimated. CONCLUSION: Female
      survivors of ALL are significantly fatter than those of other malignancies and
      healthy sibling controls. Caution should be observed in the application of
      published equations, derived from the normal population, for the calculation of
      body composition in children treated for ALL. The mechanism of onset of obesity
      remains unclear, but is probably multifactorial and related to previous cranial
      irradiation.

PMID- 11836716
TI  - Cytogenetics in pediatric low-grade astrocytomas.
AB  - BACKGROUND: Cytogenetic analysis in certain tumors is a vital part of
      classification and assignment of prognosis. Few studies have examined the value
      of cytogenetic analysis in pediatric brain tumors. This is especially true of low
      grade astrocytomas (LGA) of childhood. This study examines the correlation
      between cytogenetic abnormalities and survival in children with low-grade
      astrocytomas. The literature on adults with LGA suggest better survival for those
      whose tumors have normal cytogenetics compared to those with abnormal. We
      hypothesized this would also be true of children with low-grade astrocytomas.
      PROCEDURE: A retrospective study was performed of children presenting between
      1980 and 1998 to The Children's Hospital, Denver, who had LGA and on whose tumors
      informative cytogenetics had obtained. RESULTS: One hundred and forty-nine
      children were diagnosed with histologically proven LGA. Twenty-nine had
      successful cytogenetic analysis. One or more chromosomal abnormalities were
      observed in eight tumors while normal karyotypes were observed in 21 tumors.
      Actuarial progression-free survival at 5 years was 87.5% for the eight children
      with abnormal cytogenetics and 43% for those with normal (P=0.56). Overall
      survival at 5 years was 83% for those with abnormal cytogenetics and 78% for
      those with normal (P=0.8). The differences in progression-free survival and
      overall survival between these two groups were not significant. Those children
      with WHO Grade I tumors had significantly superior progression-free and overall
      survival than those with Grade II tumors. CONCLUSIONS: It appears unlikely that,
      for children with LGA, those with normal cytogenetics have a better prognosis
      than those with abnormal. Histologic grade is a better predictor of outcome than
      cytogenetics.

PMID- 11836717
TI  - Cholestasis, sclerosing cholangitis, and liver transplantation in Langerhans cell
      Histiocytosis.
AB  - OBJECTIVE: To analyze features and outcomes of cholestasis, sclerosing
      cholangitis (SC), and liver transplantation (LTx) in patients with Langerhans
      cell Histiocytosis (LCH) between October 1987 and June 1999. STUDY DESIGN: Of 182
      cases with LCH, 36 had hepatic involvement and 12 of those presented with
      cholestasis. These 12 were the focus of our study. Their median age was 23 months
      (range: 3-36). Hepatomegaly or hepatosplenomegaly was found in 11 of the 12;
      elevations of alkaline phosphatase, transaminases, gamma glutamyl transpeptidase
      (GGT), and less frequently direct bilirubin were detected. Sonography, liver
      biopsy, and cholangiography were consistent with the diagnosis of SC in 11
      patients. None of the biopsies revealed Langerhans cells (LC). Frequently
      associated lesions of skin, bone, and ear were noted. Early patients were treated
      with Vinblastine/prednisone for 8 weeks, later patients with the LCH I and LCH II
      protocols of the Histiocyte Society (HS). RESULTS: Median follow-up was 28 months
      (range: 10-86). Three patients improved and remained without signs of progressive
      SC at 27, 32, and 86 months. Nine had progressive liver sequelae resistant to
      chemotherapy. Of these nine, five received LTx, three died before LTx with
      progressive SC, and one awaits LTx. Three LTx patients survive without disease
      reactivation 14, 25, and 37 months post-transplant. Two patients died less than
      one month after LTx, due to renal failure and sepsis in the first patient and
      bowel volvulus with perforation followed by sepsis in the second one.
      CONCLUSIONS: SC is a frequent and usually progressive sequela of multisystem LCH
      in our institution. LTx has become the treatment of choice for the majority of
      patients and should be considered early in cases with severe hepatic involvement.

PMID- 11836718
TI  - Comparison of manual and automated leukocyte counts for determination of the
      absolute neutrophil count: application to a pediatric oncology clinic.
AB  - BACKGROUND: Determination of the absolute neutrophil count (ANC) is a critical
      test prior to initiation of chemotherapy and is a standard component of cancer
      therapy protocols. Automated determination of this parameter potentially shortens
      the turnaround time necessary between specimen phlebotomy and chemotherapy
      infusion in an outpatient setting. However, there are certain factors that can
      lead to spuriously elevated or lowered ANCs, possibly leading to inappropriate
      dosage. We therefore compared ANC results in a series of samples in which both
      automated and manual results were available. PROCEDURE: Sets of 111 specimens,
      tested over a 1-month period, had matched automated and manual ANC results
      available for initial retrospective analysis. An additional set of 35 specimens
      with ANCs of <1.5 x 10(9)/L were subsequently analyzed in a similar fashion.
      Automated ANC results were obtained with a Cell-Dyn 3500 (Abbott Diagnostics,
      Santa Clara, CA, USA) automated hematology analyzer, and manual ANC results were
      obtained using 100 cell differentials performed by 1 of 13 medical technologists.
      Results were tabulated and analyzed using standard linear regression and scatter
      plot analyses. RESULTS: Of the initial 111 specimens, automated ANC values ranged
      from 0.16-14.2 x 10(9)/L (median=2.6 x 10(9)/L), as compared with 0.24-13.9 x
      10(9)/L (median 3.0 x 10(9)/L) for manual ANC values (R(2) = 0.99; SE=0.49).
      Differences between the ANC values ranged from -55 to +33% (SD=14%) of the manual
      value. Of the second set of 35 specimens, regression analysis yielded an R(2)
      value of 0.92, with a SE of 0.11. Both data sets yielded acceptable degrees of
      variation on scatter plot analyses. CONCLUSIONS: Automated ANC values appear
      adequate for determining suitability for chemotherapy and lessen the turnaround
      time between specimen phlebotomy and result verification.

PMID- 11836719
TI  - Placental site trophoblastic tumor (PSTT) in mother and child: first report of
      PSTT in infancy.
AB  - BACKGROUND: To the authors' knowledge, placental site trophoblastic tumors
      occurring simultaneously in mother and infant have not previously been reported.
      PROCEDURE: The clinicopathologic features of metastatic placental site
      trophoblastic tumor in a mother and her 4-month-old son are described. RESULTS:
      The disease in the infant was aggressive, and he died in multiorgan failure
      within 5 weeks of hospital admission. Autopsy showed widespread metastases to
      liver, lungs, pleura, kidney, mesentery and lymph nodes. The mother, who had a
      uterine tumor and lung metastases, was treated with chemotherapy and hysterectomy
      and has no evidence of disease 26 months post-treatment. CONCLUSIONS: This report
      shows that placental site trophoblastic tumors can metastasize in both mother and
      child.

PMID- 11836723
TI  - Informed consent--East meets West--worlds apart?

PMID- 11836721
TI  - Neuroblastoma in a patient with the Beckwith-Wiedemann syndrome (BWS).

PMID- 11836724
TI  - Infantile choriocarcinoma with idiopathic massive fetomaternal hemorrhage.

PMID- 11836728
TI  - CNS embryonal sarcoma.

PMID- 11836725
TI  - Single signal of the Williams syndrome chromosome region 1 gene in hyperploidic
      bone marrow cells of acute lymphoblastic leukemia in a Williams syndrome patient.

PMID- 11836726
TI  - Postoperative intussusception: an overlooked complication in pediatric surgical
      oncology.

PMID- 11836727
TI  - Risk of dying of retinoblastoma in Mexican children.

PMID- 11836730
TI  - Exact group-sequential designs for clinical trials with randomized play-the
      winner allocation.
AB  - The use of both sequential designs and adaptive treatment allocation are
      effective in reducing the number of patients receiving an inferior treatment in a
      clinical trial. In large samples, when the asymptotic normality of test
      statistics can be utilized, a standard sequential design can be combined with
      adaptive allocation. In small samples the planned error rate constraints may not
      be satisfied if normality is assumed. We address this problem by constructing
      sequential stopping rules with specified properties by consideration of the exact
      distribution of test statistics under a particular adaptive allocation scheme,
      the randomized play-the-winner rule. Using this approach, compared to traditional
      equal allocation trials, trials with adaptive allocation are shown to require a
      larger total sample size to achieve a given power. More interestingly, the
      expected number patients allocated to the inferior treatment may also be larger
      for the adaptive allocation designs depending on the true success rates.

PMID- 11836731
TI  - Model-based estimation of vaccine effects from community vaccine trials.
AB  - Community vaccine trials are becoming increasingly important to assess both the
      direct and indirect community level effects of vaccination. In this paper, we
      present statistical methods to analyse such trials, using a design with several
      matched pairs of communities. The communities are matched on similarities in
      infection transmission as reflected through the basic reproduction number. Two
      methods of analysis are presented and compared. The first is simple empirical
      estimation of vaccine effects. Summary measures of these effects are constructed
      by reciprocal variance weighted averages across the community pairs. The second
      is likelihood-based where we derive a mixed effects epidemic model. This model
      takes the intercommunity variability into account through a random effect on the
      basic reproduction number. With this model, we derive a distribution-free
      estimator for the variance of the random effect. We use simulated epidemics to
      explore the performance of the two estimation methods for different numbers of
      community pairs and different levels of inter-pair variability. Both methods
      provide acceptable estimates in terms of bias and precision under reasonable
      conditions. Although the empirical approach involves fewer assumptions than the
      model-based approach, the resulting vaccine effectiveness estimates are only
      applicable to the vaccination fraction tested in the trial. In contrast, the
      model-based approach can be used to predict the vaccine effectiveness at
      vaccination fractions other than those used in the trial. Thus, it can be used as
      a public health policy tool for predicting the community level effects of
      vaccination. We demonstrate such use by predicting total vaccine effectiveness
      for the whole range of vaccination fractions.

PMID- 11836732
TI  - Score tests for detecting excess risks around putative sources.
AB  - Focused clustering studies examine raised disease risk around prespecified point
      sources. As statistical methods to detect such clusters, Stone's maximum
      likelihood ratio test is popular, against the general ordered alternatives and
      score tests which score each case the reciprocal of the distance from a point
      source as a surrogate exposure. This paper considers extensions of score tests in
      that (i) they can allow us to select the best among prespecified parametric
      exposure functions to avoid multiple testing problems and (ii) they can be
      applied to a possible situation where the hazardous substance levels have a peak
      at some distance from a point source. Simulation studies show that the powers of
      the proposed tests are higher than that of Stone's test over all the alternatives
      considered. The proposed tests are illustrated with hypothetical data as well as
      simulated data to be expected in an epidemiological study currently in progress
      regarding an excess risk of perinatal undesirable outcomes near municipal solid
      waste incinerators in Japan.

PMID- 11836733
TI  - Selection effects in randomized trials with count data.
AB  - Selection criteria are specified in clinical trials to define the study
      population from which the sample will be obtained. It is common for one of these
      criteria to be based on historical or baseline measurements of the clinical sign
      or symptom that will serve as the response variable in the trial. The effect of
      such selection criteria has been studied extensively for normally distributed
      responses, but less is known about the situation in which the response is a count
      or a possibly recurrent event. In this paper we examine the bias and relative
      efficiency of some common methods of analysis for count data in the presence of
      selection criteria. The investigation is carried out using asymptotic theory
      pertaining to misspecified models and by simulation. Applications involving data
      from an epilepsy trial and a study of transient myocardial ischaemia illustrate
      the effect of ignoring the selection mechanism.

PMID- 11836734
TI  - Population toxicokinetic analysis of 2,3,7,8-tetrachlorodibenzo-p-dioxin using
      Bayesian techniques.
AB  - Understanding the kinetics of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)
      concentrations in humans is an important step for TCDD cancer risk assessment. In
      this paper longitudinal series of serum TCDD concentration measurements on U.S.
      veterans of the Vietnam war, who were exposed to dioxin during herbicide-spraying
      operations, are studied. The overall aim is to use these data to infer the
      dynamics of TCDD concentrations in humans. This is done by identifying a kinetic
      model describing the dioxin time course at the individual level. The individual
      toxicokinetic model is then expanded into a population model within a Bayesian
      hierarchical framework which allows residual variations across subjects that
      cannot be explained by observed covariates. Other complications in the data, such
      as unknown exposure histories, are also resolved implicitly through the
      hierarchical model. Moreover, the choice of a Bayesian approach enables the
      accumulation of external source of information in the form of prior
      distributions. The model is subjected to various diagnostic checks and analyses
      of sensitivity to distributional assumptions showing a good fit in terms of both
      the population and the kinetic features.

PMID- 11836735
TI  - A Bayesian analysis of bivariate ordinal data: Wisconsin epidemiologic study of
      diabetic retinopathy revisited.
AB  - In many biomedical experiments one may often encounter bivariate data which are
      component-wise ordinal. The data set of the ophthalmologic experiment of the
      Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR) is an example of
      such data. Several authors considered the analysis of such data from different
      viewpoints. The present work reviews the existing literature based on the WESDR
      data and on the basis of some latent variables provide the technique for
      analysing such data more easily in a Bayesian framework. Computation supports the
      methodology to a great extent. A comparison between our approach and the
      likelihood based approach considered by Kim has also been made.

PMID- 11836741
TI  - Proceedings of the 2nd European Meeting on Brainstem Reflexes, Functions, and
      Related Movement Disorders. Amsterdam, The Netherlands, April 2001.

PMID- 11836736
TI  - Prospective prediction in the presence of missing data.
AB  - A variety of methods and algorithms are available for estimating parameters in
      the class of a generalized linear model in the presence of missing values.
      However, there is little information on how this already built model can be used
      for prediction in new observations with missing data in the covariates. Dropping
      the observations with missing values is a widespread practice with serious
      statistical and non-statistical implications. One solution is to fit separate
      regression models, or submodels, to each pattern of missing covariates. In
      practice, for any iterative regression method, this approach is computationally
      intensive. We propose a simple methodology to predict outcomes for individuals
      with incomplete information based on the estimated coefficients and covariance
      from the already built model. This method does not require revisiting the
      original data set used to build the original model and works by generating a
      first-order approximation of any submodel coefficient estimates. This is achieved
      by using the SWEEP operator on an augmented covariance matrix obtained from the
      original model. We refer to this approach as the one-step sweep (OSS) method. The
      methodology is demonstrated using data from the Department of Veterans Affairs
      Continuous Improvement in Cardiac Surgery Program (CICSP). These data contain 30
      day mortality, the outcome of interest, and risk information for over 14,000
      patients who underwent coronary artery bypass grafting (CABG) surgery over a four
      year period. Using complete data from the first 3.5 years of this study period, a
      logistic regression model was built. This model was then used to predict
      mortality for patients undergoing CABG in the most recent 6-months. In order to
      evaluate the performance of the OSS method we randomly generated observations
      with missing covariates in the 6-month prediction database. We use this
      simulation to demonstrate that the computationally efficient OSS substantially
      reduces the error in risk-adjusted mortality created when cases with incomplete
      information are eliminated. Lastly, we derive the relationship between the OSS
      method and data imputation.

PMID- 11836738
TI  - Advanced methods in meta-analysis: multivariate approach and meta-regression.
AB  - This tutorial on advanced statistical methods for meta-analysis can be seen as a
      sequel to the recent Tutorial in Biostatistics on meta-analysis by Normand, which
      focused on elementary methods. Within the framework of the general linear mixed
      model using approximate likelihood, we discuss methods to analyse univariate as
      well as bivariate treatment effects in meta-analyses as well as meta-regression
      methods. Several extensions of the models are discussed, like exact likelihood,
      non-normal mixtures and multiple endpoints. We end with a discussion about the
      use of Bayesian methods in meta-analysis. All methods are illustrated by a meta
      analysis concerning the efficacy of BCG vaccine against tuberculosis. All
      analyses that use approximate likelihood can be carried out by standard software.
      We demonstrate how the models can be fitted using SAS Proc Mixed.

PMID- 11836739
TI  - A flexible design for multiple armed screening trials by Daniel J. Sargent and
      Richard M. Goldberg, Statistics in Medicine 2001; 20: 1051-1060.

PMID- 11836742
TI  - Oculomotor system: a dual innervation of the eye muscles from the abducens,
      trochlear, and oculomotor nuclei.

PMID- 11836746
TI  - Magnetic resonance imaging of the brainstem and cranial nerves III-VII.

PMID- 11836743
TI  - The eyelid levator muscle: servant of two masters.

PMID- 11836747
TI  - Trigeminal reflexes.

PMID- 11836745
TI  - Emotional innervation of facial musculature.

PMID- 11836744
TI  - Afferent innervation of eyelids and their connections to the superior colliculus.

PMID- 11836748
TI  - Cortical control of brainstem motor systems.

PMID- 11836749
TI  - Role of brainstem-spinal projections in voluntary movement.

PMID- 11836751
TI  - Neural organization of eyelid responses.

PMID- 11836750
TI  - Origin of eye and eyelid movements during blinking.

PMID- 11836752
TI  - Trigeminal neuralgia: update on reflex and evoked potential studies.

PMID- 11836737
TI  - Repeated measures models for prescribing change.
AB  - Linear mixed models are used to detect a change, if any, in prescribing habits at
      the primary care practice level due to an educational intervention given repeated
      measures data before and after intervention and a control group. Inferences are
      corrected for general practice size, fundholding status and baseline prescribing.
      The correlation structure is discussed and the results for multilevel modelling
      using MLwiN and NLME version 3.0 are compared.

PMID- 11836753
TI  - Trigeminal nociceptive reflexes.

PMID- 11836754
TI  - Masseter reflexes modulated by pain.

PMID- 11836756
TI  - Hypoglossal-facial anastomosis induced central plastic changes in the blink
      reflex circuitry.

PMID- 11836757
TI  - Vestibular brainstem disorders: clinical syndromes in roll plane and their model
      simulation.

PMID- 11836759
TI  - Sleep bruxism as a motor disorder.

PMID- 11836758
TI  - Clinical spectrum and physiology of palatal tremor.

PMID- 11836755
TI  - Facial palsy, postparalytic facial syndrome, and hemifacial spasm.

PMID- 11836762
TI  - The startle syndrome.

PMID- 11836760
TI  - Pathophysiology and treatment of cranial dystonia.

PMID- 11836761
TI  - Dry eye, blinking, and blepharospasm.

PMID- 11836763
TI  - Neurosurgical treatment modalities in Parkinson's disease.

PMID- 11836764
TI  - Physiological and pathological aspects of oropharyngeal swallowing.

PMID- 11836766
TI  - Time evolution of cerebral perfusion and apparent diffusion coefficient measured
      by magnetic resonance imaging in a porcine stroke model.
AB  - PURPOSE: To demonstrate the feasibility of sequential diffusion-weighted (DW) and
      perfusion-weighted (PW) magnetic resonance imaging (MRI) of a recently developed
      porcine stroke model and to evaluate the evolution of cerebral perfusion and the
      apparent diffusion coefficient (ADC) over time. Materials and Methods In five
      pigs, DW imaging (DWI) and PW imaging (PWI) was carried out for 7 hours after
      stroke onset, starting 1 hour after middle cerebral artery occlusion (MCAO).
      RESULTS: The DWI lesion volume increased significantly with time, and final DWI
      lesion volume correlated well with lesion area on histological sections (r =
      0.910). T2 changes could be recognized 3 hours after stroke onset. At 1 hour the
      ADC ratio (ischemic lesion/contralateral side) was reduced to 0.81 in the caudate
      putamen and to 0.87 in the cortex, and the cerebral blood flow ratio was reduced
      to 0.40 in the caudate-putamen and 0.51 in the cortex. CONCLUSION: The level of
      flow reduction in the caudate-putamen and the cortex after 1 hour is in good
      correlation with human thresholds of irreversible and reversible ischemic damage,
      and accordingly, this model might be a model for mechanisms of infarct evolution
      and therapeutic intervention.

PMID- 11836767
TI  - Investigation of mechanisms underlying transient T2 normalization in longitudinal
      studies of ischemic stroke.
AB  - PURPOSE: To determine if the phenomenon of transient normalization of T2
      relaxation in the subacute stage of ischemic stroke is associated with either
      magnetic susceptibility effects secondary to hemorrhage or changes in tissue
      water content. MATERIALS AND METHODS: We utilized a rat model of transient,
      focal, cerebral ischemia. The possibility of hemorrhage was evaluated with T2*
      weighted (T2*W) imaging and histology. Changes in water content were assessed by
      brain wet-to-dry weight. RESULTS: Susceptibility effects were not evident in T2*W
      images, and neither red blood cells nor unchelated Fe(III) was found in
      hematoxylin and eosin (H-E)- or Prussian Blue-stained sections, respectively.
      However, between the peak of T2 contrast and the point of transient T2
      normalization, water content consistently decreased by an average of 3%.
      CONCLUSION: Transient T2 normalization is associated with normalization of water
      content and can occur without evidence of hemorrhage.

PMID- 11836768
TI  - In vivo quantitative proton MRSI study of brain development from childhood to
      adolescence.
AB  - PURPOSE: To quantify regional variations in metabolite levels in the developing
      brain using quantitative proton MR spectroscopic imaging (MRSI). MATERIALS AND
      METHODS: Fifteen healthy subjects three to 19 years old were examined by in vivo
      multislice proton MRSI. Concentrations of N-acetyl aspartate (NAA), total choline
      (Cho), total creatine (Cr), and peak area ratios were determined in selected
      frontal and parietal gray and white matter regions, basal ganglia, and thalamus.
      RESULTS: In cortical gray matter regions, the ratio of NAA/Cho increased to a
      maximum at 10 years and decreased thereafter (P = 0.010). In contrast, in white
      matter, average ratios NAA/Cho increased linearly with age (P = 0.045). In
      individual brain regions, age-related changes in NAA/Cho were found in the
      putamen (P = 0.044). No significant age-related changes in NAA, Cho, Cr, or other
      metabolite ratios could be determined. CONCLUSION: Consistent with recent studies
      using other structural and functional neuroimaging techniques, our data suggest
      that small but significant changes occur in regional cerebral metabolism during
      childhood and adolescence. Non-linear age related changes of NAA/Cho in frontal
      and parietal areas, resembling previously reported age related changes in rates
      of glucose utilization and cortical volumes, may be associated with dendritic and
      synaptic development and regression. Linear age-related changes of NAA/Cho in
      white matter are also in agreement with age-related increases in white matter
      volumes, and may reflect progressive increases in axonal diameter and
      myelination.

PMID- 11836769
TI  - Whole brain apparent diffusion coefficient histogram: a new tool for evaluation
      of leukoaraiosis.
AB  - PURPOSE: To test whole brain apparent diffusion coefficient histogram analysis as
      an alternative approach to visual score for the assessment of leukoaraiosis (LA).
      MATERIALS AND METHODS: T2 and diffusion weighted images were obtained in 15
      elderly patients. LA extension was assessed on T2 weighted images by two
      observers using a semiquantitative visual score. Apparent diffusion coefficient
      (ADC) maps of the entire brain were generated and, after exclusion of the skull
      with manual tracing and of the cerebrospinal fluid (CSF) by application of a
      threshold value, whole brain (WB)-ADC histogram was obtained. Moreover, a brain
      volume index (BVI) was calculated on ADC maps as (intracranial volume - CSF
      volume) /intracranial volume. RESULTS: The kappa inter-observer agreement for LA
      scoring was 0.69. Manual segmentation of the skull showed a mean inter-operator
      coefficient of variation below 3%. The median value of whole brain ADC histogram
      directly correlated with LA extension (P = 0.013). Moreover a significant inverse
      correlation (P = 0.002) was found between WB-ADC median value and BVI.
      CONCLUSION: WB-ADC histogram is a reproducible alternative tool for assessing LA
      extension and severity.

PMID- 11836771
TI  - Correlation of single-lumen silicone implant integrity with chemical shift
      artifact on T2-weighted magnetic resonance images.
AB  - PURPOSE: To correlate the integrity of single-lumen silicone gel implants with
      chemical shift artifact (CSA) associated with infolding of the elastomer shell.
      MATERIALS AND METHODS: The T2-weighted images of presurgical MRI examinations of
      54 implants were retrospectively reviewed by two breast radiologists blinded to
      the operative and pathologic findings. CSA associated with intraluminal membranes
      was quantified by determining the fraction of membranes with it and categorized
      as minimal (0-1/3 of membranes involved), moderate (>1/3- <2/3), and marked (2/3
      to all). CSA was qualified by noting whether CSA intensity of the membranes was
      less than or similar to that of blood vessels. The CSA was correlated with the
      surgical or pathology findings to judge integrity of the implant. RESULTS:
      Nineteen implants were intact, 35 were dysfunctional (gel leakage or rupture).
      Twenty-eight of 29 (97%) with a minimal fraction of membranes with CSA were
      dysfunctional; 17/21 (81%) with CSA associated with a marked fraction of
      membranes were intact (P < 0.001). All 28 implants with CSA intensity less than
      vessels were dysfunctional, 19/26 (73%) with CSA equal to vessels were intact (P
      < 0.001). All 25 implants with minimal CSA and intensity less than vessels were
      dysfunctional. Seventeen of 19 (89%) implants with CSA associated with a marked
      fraction of membranes and intensity equal to vessels were intact (P = 0.02). The
      magnetic resonance imaging (MRI) signs were combined with strong CSA as a
      predictor of integrity, and 22 of 26 (85%) implants were correctly diagnosed, 4
      dysfunctional and 18 intact (P < 0.0001). CONCLUSION: CSA correlates with
      integrity of silicone gel implants on T2-weighted images and can be used with
      other MRI signs to improve diagnosis.

PMID- 11836770
TI  - MRI detection of myocardial perfusion defects due to coronary artery stenosis
      with MS-325.
AB  - PURPOSE: To assess the value of an intravascular, albumin-targeted contrast
      agent, MS-325, in visualizing myocardial ischemia with magnetic resonance imaging
      (MRI). MATERIALS AND METHODS: Left anterior descending coronary artery (LAD)
      stenosis was created in 19 pigs using a closed-chest modified angioplasty
      technique. Myocardial ischemia was detected by first-pass, contrast-enhanced MRI
      at peak dipyridamole stress and was compared to Technetium-99m (Tc-99m) sestamibi
      single photon emission computed tomography (SPECT). Regional coronary blood flow
      was determined using microspheres. RESULTS: Inducible myocardial ischemia with
      >40% reduction in stress myocardial blood flow was created in eight animals. An
      MRI defect, classified as > or=75% reduction in peak myocardial signal intensity
      in the affected territory, was detected in 92.3% of these animals. In the
      presence of mild coronary stenosis, there was uniform enhancement with MRI and
      tracer uptake by SPECT. Concordance of MRI and SPECT for detecting perfusion
      defects was 85%. CONCLUSION: The pattern of prolonged and persistent MR
      hypoenhancement of the ischemic myocardial bed using MS-325, which is retained
      primarily in the vascular bed due to its albumin-binding properties, facilitates
      the detection of myocardial perfusion defects.

PMID- 11836772
TI  - Magnetic resonance imaging of inflammatory bowel disease: evaluation in a rabbit
      model.
AB  - PURPOSE: To correlate intestinal contrast enhancement and wall thickening with
      the degree of inflammation in an experimental model of inflammatory bowel
      disease. MATERIALS AND METHODS: Inflammatory bowel disease was elicited in 39 New
      Zealand White rabbits by rectal instillation of 2,4,6-trinitrobenzene sulphonic
      acid (TNBA). Magnetic resonance imaging (MRI) was used to determine bowel wall
      thickness and intestinal contrast enhancement after the administration of 0.1
      mmol/kg of gadodiamide intravenously. MR measurements were compared with the
      complete histopathologic analysis. RESULTS: MR measurements of bowel wall
      thickness correlated well with histopathologic measurements in vitro (r = 0.85, P
      < 0.0001) and with histopathologic evidence of chronic inflammatory bowel disease
      (P < 0.02). Chronic inflammation was characterized by increased intestinal
      contrast enhancement (137 +/- 25%) when compared to normal bowel (86 +/- 7%, P =
      0.04). CONCLUSION: Contrast-enhanced MRI accurately reflects inflammatory bowel
      disease in the rabbit model.

PMID- 11836773
TI  - Measurement of renal volumes with contrast-enhanced MRI.
AB  - PURPOSE: To determine the accuracy of in vivo magnetic resonance imaging (MRI)
      measurement of total renal parenchymal volume and medullary fraction. MATERIALS
      AND METHODS: Sixteen kidneys in eight pigs were imaged with a multiphasic
      contrast-enhanced fast three-dimensional sequence on a 1.5-T imager. Kidney
      segmentation, followed by a process of signal intensity thresholding for cortical
      and nephrographic phase datasets, allowed for MRI measurements of parenchymal
      volume and medullary fraction. Autopsy provided reference standards of renal
      volume, weight, and medullary fraction. RESULTS: An excellent correlation was
      found between MRI measurement of total renal parenchymal volume and autopsy
      volume (R2 = 0.86) and weight (R2 = 0.90). Medullary fraction (mean +/- SD)
      measured with MRI was 0.120 +/- 0.067, and with autopsy was 0.116 +/- 0.025 (t
      test P = 0.84, F-test P = 0.001). CONCLUSION: MRI measurements of total renal
      volume are accurate. MRI measurements of medullary fraction show promise, but
      precision is limited when using a simple signal intensity thresholding algorithm.

PMID- 11836774
TI  - Magnetic resonance imaging and permanent cosmetics (tattoos): survey of
      complications and adverse events.
AB  - PURPOSE: To use a survey to determine the incidence of complications and adverse
      events in individuals with permanent cosmetics (e.g., tattooed eyeliner,
      eyebrows, lips, cheeks, etc.) who underwent magnetic resonance (MR) imaging.
      MATERIALS AND METHODS: A questionnaire was distributed to clients of cosmetic
      tattoo technicians. This survey asked study subjects for demographic data,
      information about their tattoos, and for their experiences during MR imaging
      procedures. RESULTS: Data obtained from 1032 surveys were tabulated. One hundred
      thirty-five (13.1%) study subjects underwent MR imaging after having permanent
      cosmetics applied. Of these, only two individuals (1.5%) experienced problems
      associated with MR imaging. One subject reported a sensation of "slight tingling"
      and the other subject reported a sensation of "burning"; both sensations were
      transient in nature. CONCLUSION: Based on these findings and information in the
      peer-reviewed literature, it appears that MR imaging may be performed in patients
      with permanent cosmetics without any serious soft tissue reactions or adverse
      events. Therefore, the presence of permanent cosmetics should not prevent a
      patient from undergoing MR imaging.

PMID- 11836775
TI  - Magnetic resonance imaging-guided focused ultrasound thermal therapy in
      experimental animal models: correlation of ablation volumes with pathology in
      rabbit muscle and VX2 tumors.
AB  - PURPOSE: To further investigate the use of magnetic resonance-guided focused
      ultrasound therapy (MRgFUS) as a noninvasive alternative to surgery in the local
      control of soft-tissue tumors by ablating prescribed volumes of VX2 rabbit tumors
      and comparing with ablation of normal tissue volumes. MATERIALS AND METHODS:
      Small, ellipsoidal ablations at shallow depth were created using 5- to 15-second
      sonication pulses at radio frequency (RF) powers of 50-125 W using a spherical,
      air-backed transducer operating at 1.463 MHz under MR guidance in a 1.5-T
      clinical scanner. RESULTS: Excellent correlation was observed between prescribed
      treatment volumes, MR thermal dosimetry, post-treatment verification MRI, and
      histopathology. Multifocal ablations of VX2 tumors in rabbits at depths of up to
      2.5 cm resulted in complete ablation of the prescribed treatment volume.
      CONCLUSION: MRgFUS is an effective technique for treating tumors in vivo.
      Techniques developed for treatments in homogeneous tissue volumes are applicable
      in the more complicated tumor environment if MR temperature feedback is available
      to modify treatment delivery parameters.

PMID- 11836776
TI  - Mycotic aortocaval fistula: efficient evaluation by bolus-chase MR angiography.
AB  - Aortocaval fistula (ACF) is a rare but life-threatening condition. This case
      report describes the use of bolus-chase gadolinium-enhanced 3D magnetic resonance
      angiography (MRA) to provide an efficient evaluation of a patient with ACF
      associated with a mycotic abdominal aortic aneurysm. This case highlights the
      ability of bolus-chase MRA to provide both the specific diagnosis of ACF as well
      as the information necessary for extra-anatomic arterial bypass. Bolus-chase MRA
      is a promising method for the evaluation of patients with this disease entity.

PMID- 11836777
TI  - Pseudothrombosis with T2-weighted fast spin-echo MR images caused by static
      portal venous flow in severe cirrhosis.
AB  - Unenhanced T2-weighted fast spin-echo images obtained in a 65-year-old woman with
      severe cirrhosis showed an area of high signal intensity occupying the left
      second-order portal vein branch, suggesting portal vein thrombosis in cirrhosis.
      Doppler sonography, which revealed virtually no blood flow in the vessel, also
      supported the diagnosis. Gadolinium-enhanced MRI subsequently revealed the
      patency of the vessel. The extremely slow portal venous flow was considered to be
      the cause of false-positive findings with unenhanced MRI and sonography.

PMID- 11836778
TI  - Quantitative analysis of MRI signal abnormalities of brain white matter with high
      reproducibility and accuracy.
AB  - PURPOSE: To assess the reproducibility and accuracy compared to radiologists of
      three automated segmentation pipelines for quantitative magnetic resonance
      imaging (MRI) measurement of brain white matter signal abnormalities (WMSA).
      MATERIALS AND METHODS: WMSA segmentation was performed on pairs of whole brain
      scans from 20 patients with multiple sclerosis (MS) and 10 older subjects who
      were positioned and imaged twice within 30 minutes. Radiologist outlines of WMSA
      on 20 sections from 16 patients were compared with the corresponding results of
      each segmentation method. RESULTS: The segmentation method combining expectation
      maximization (EM) tissue segmentation, template-driven segmentation (TDS), and
      partial volume effect correction (PVEC) demonstrated the highest accuracy (the
      absolute value of the Z-score was 0.99 for both groups of subjects), as well as
      high interscan reproducibility (repeatability coefficient was 0.68 mL in MS
      patients and 1.49 mL in aging subjects). CONCLUSION: The addition of TDS to the
      EM segmentation and PVEC algorithms significantly improved the accuracy of WMSA
      volume measurements, while also improving measurement reproducibility.

PMID- 11836779
TI  - Single breath-hold extended free-breathing navigator-gated three-dimensional
      coronary MRA.
AB  - PURPOSE: To acquire the center of k-space while extending three-dimensional free
      breathing navigator-gated coronary magnetic resonance (MR) angiography by an
      initial single breath-hold. MATERIALS AND METHODS: This approach was successfully
      applied in eight healthy adult subjects. Resulting images were compared with
      conventionally acquired free-breathing navigator-gated MR angiograms. RESULTS:
      The acquisition of k-space center during the single breath-hold resulted in a 26%
      increase (P < 0.05) of signal-to-noise ratio. Visible length of the right
      coronary artery, as well as contrast-to-noise ratio between the blood and the
      myocardial muscle, were identical. CONCLUSION: The breath-hold extension was
      shown to be a valuable technique that may be combined with first-pass contrast
      enhanced MR imaging.

PMID- 11836780
TI  - Sodium T2* relaxation times in human heart muscle.
AB  - PURPOSE: To determine sodium transverse relaxation (T2*) characteristics for
      myocardium, blood and cartilage in humans. METHODS: T2* measurements were
      performed using a 3D ECG-gated spoiled gradient echo sequence. A 1.5 Tesla
      clinical scanner and a 23Na heart surface coil were used to examine eight healthy
      volunteers. In biological tissue, the sodium 23 nucleus exhibits a two-component
      T2 relaxation due to the spin 3/2 and its quadrupolar nature. The long T2*
      components of normal myocardium, blood, and cartilage were quantified. For
      myocardium, the T2* was determined separately for the septum, anterior wall,
      lateral wall, and posterior wall. RESULTS: The long T2* relaxation time
      components of 13.3 +/- 4.3 msec (septum 13.9 +/- 3.2 msec, anterior wall 13.8 +/-
      5.4 msec, lateral wall 11.4 +/- 4.1 msec, posterior wall 14.1 +/- 3.7 msec), 19.3
      +/- 3.3 msec, and 10.2 +/- 1.6 msec, were significantly different for myocardium,
      blood, and cartilage, respectively (P < 0.00001, Friedman's ANOVA). CONCLUSION:
      Measurement of 23Na T2* relaxation times is feasible for different regions of the
      human heart muscle, which might be useful for the evaluation of cardiac
      pathologies.

PMID- 11836781
TI  - Reproducibility of in vivo metabolite quantification with proton magnetic
      resonance spectroscopic imaging.
AB  - PURPOSE: To investigate intra- and interscanner in vivo reproducibility of brain
      metabolite quantification using 1H magnetic resonance spectroscopic imaging (1H
      MRSI) (PRESS localization, TE = 30 msec, voxel volume = 2.3 mL) and the linear
      combination model (LCModel). MATERIALS AND METHODS: One subject had a total of
      nine scans on three occasions at a single site, and three subjects had single
      scans at two sites. Coefficients of variation (CVs) were estimated using
      different statistical models applied to intra- and interscanner data; therefore,
      only qualitative comparisons may be made between results. RESULTS: CV (intra
      /interscanner) for metabolite quantifications were choline, 12.3%/10.1%;
      creatine, 9.9%/10.6%; glutamate + glutamine, 15.8%/13.6%; myo-inositol,
      18.5%/14.7%; and N-acetyl-aspartate + N-acetyl-aspartyl-glutamate, 6.1%/7.0%.
      Overall, total intra- and intersubject variability was greater than intra- and
      interscanner variability. CONCLUSION: When quantifying metabolic concentrations
      using the methods employed in this study, biological factors contribute a greater
      proportion to measurement variability than measurement errors. Using this
      technique, intra- and intersite measurement errors are of the same order.

PMID- 11836782
TI  - Hepatocyte growth factor is essential for migration of myogenic cells and
      promotes their proliferation during the early periods of tongue morphogenesis in
      mouse embryos.
AB  - Temporal and spatial occurrence of hepatocyte growth factor (HGF) and its cognate
      receptor c-Met in the mouse mandibular development was investigated by
      immunohistochemistry and quantitative reverse transcriptase-polymerase chain
      reaction. HGF was first recognized in the mesenchymal cells of the first
      branchial arch at the 10th day of gestation (E10), before tongue formation,
      whereas HGF receptor (c-Met) -positive myogenic cells first appeared at E11 in
      the center of mandibles. By E12, HGF turned to be colocalized with c-Met in the
      differentiating tongue myoblasts. Between E14 and E16, HGF disappeared, whereas c
      Met remained, in the tongue myoblasts. The levels of HGF mRNA in the developing
      tongue decreased in accordance with the increase of desmin mRNA levels from E11
      to E17. These in vivo results strongly suggest that the HGF/c-Met system takes
      part in the earlier stages of tongue development. To elucidate this hypothesis,
      the antisense oligodeoxyribonucleotide (A-ODN) for mouse HGF mRNA was added to
      the organ culture system of mandible with serumless, defined medium. Mandibular
      arches from E10 mouse embryos were cultured at 37 degrees C for 10 days in the
      absence or presence of A-ODN, control (sense) oligonucleotide (C-ODN), or A-ODN
      plus recombinant HGF. In the control mandibular explants cultured without HGF or
      ODN, the anterior two-third of the tongue derived from the first branchial arch
      was formed. It contained abundant desmin-positive myoblasts and was equivalent to
      the tongue of E14-E15. In contrast, in the presence of A-ODN in the medium,
      neither the swelling nor myogenic cells were found in the tongue-forming region
      of explants, and myogenic cells accumulated behind the tongue-forming region.
      Such dysplasia of tongue was never induced in the presence of C-ODN or A-ODN plus
      recombinant HGF in the medium. The effect of A-ODN appeared to be developmental
      stage-specific, because tongue dysplasia occurred when A-ODN was present during
      the earlier 4 days but not during the later 4 days of the culture. Furthermore,
      recombinant HGF added to the culture without ODNs during the earlier 4 days
      caused elevation in the number of mitotic myoblasts. These results suggest that
      HGF regulates both the migration and proliferation of myogenic cells during the
      earlier stages of tongue development.

PMID- 11836783
TI  - Formation and maintenance of distinctive cell patterns by coexpression of
      membrane-bound ligands and their receptors.
AB  - We show that graded or checkerboard-like cell patterns, and segmental domains
      along a body axis, can be generated by cell behaviors involving differences in
      intercellular repulsion. A membrane-bound signal transduction system mediating
      contact-dependent cell interactions includes membrane-bound ligands (ephrins) and
      their receptors with tyrosine-kinase activity (Eph proteins). These molecules
      mediate both repulsive and attractive interactions under bilateral threshold
      control, i.e., cells expressing the receptors adhere to a surface bearing a
      critical density of ligand reciprocal to the density of receptor but are repelled
      by a surface with other densities of ligand (Honda [1998] J. Theor. Biol. 192:235
      246). We extend this model. General membrane-bound ligands (not always ephrins)
      and their receptors are presumably coexpressed in a single cell under bilateral
      threshold control. Computer simulations of cell pattern formation showed that
      when coexpression of the ligand and receptor is reciprocal, the cells self
      organize into a pattern of segmental domains or a graded cell arrangement along
      the body axis. The latter process interprets positional information in terms of
      protein molecules. When coexpression of the two species of molecules is not
      always reciprocal, the cells generate various patterns including checkerboard and
      kagome (star) patterns. The case of separate expression of ligands and receptors
      in different cells is also examined. The mechanism of differences in cell
      repulsion is compared with the differential cell adhesion hypothesis, which has
      been used to explain cell sorting.

PMID- 11836784
TI  - Expression of fibroblast growth factors 4, 8, and 10 in limbs, flanks, and
      blastemas of Ambystoma.
AB  - Members of the fibroblast growth factor (FGF) family of molecules are critical to
      limb outgrowth. Here, we examine the expression of Fgfs in three types of limbs
      embryonic (developing), mature (differentiated), and regenerating-as well as in
      the surrounding non-limb tissues in the Mexican axolotl, Ambystoma mexicanum. We
      have previously cloned partial cDNAs of Fgf4, 8, and 10 from the axolotl
      (Christensen et al., 2001); the complete Fgf10 cDNA sequence is presented here.
      Axolotl Fgf10 showed deduced amino acid sequence identity with all other
      vertebrate Fgf10 coding sequences of >62%, and also included conserved 5' and 3'
      untranslated regions in nucleotide sequence comparisons. Semiquantitative reverse
      transcriptase-polymerase chain reaction showed that fibroblast growth factors are
      differentially expressed in axolotl limbs. Only Fgf8 and 10 were highly expressed
      during axolotl limb development, although Fgf4, 8, and 10 are all highly
      expressed during limb development of other vertebrates. Fgf4 expression, however,
      was highly expressed in the differentiated salamander limb, whereas expression
      levels of Fgf8 and 10 decreased. Expression levels of Fgf8 and 10 then increased
      during limb regeneration, whereas Fgf4 expression was completely absent. In
      addition, axolotl limb regeneration contrasted to limb development of other
      vertebrates in that Fgf8 did not seem to be as highly expressed in the distal
      epithelium; rather, its highest expression was found in the blastema mesenchyme.
      Finally, we investigated the expression of these Fgfs in non-limb tissues. The
      Fgfs were clearly expressed in developing flank tissue and then severely
      downregulated in mature flank tissue. Differential Fgf expression levels in the
      limb and shoulder (limb field) versus in the flank (non-limb field) suggest that
      FGFs may be instrumental during limb field specification as well as instrumental
      in maintaining the salamander limb in a state of preparation for regeneration.

PMID- 11836785
TI  - Green fluorescent protein expression in germ-line transmitted transgenic
      zebrafish under a stratified epithelial promoter from keratin8.
AB  - A zebrafish cDNA encoding a novel keratin protein was characterized and named
      keratin8, or krt8. krt8 expression was initiated at 4.5 hr postfertilization,
      immediately after the time of zygotic genome activation. The expression is
      limited to a single layer of envelope cells on the surface of embryos and, in
      later stages, it also appears in the innermost epithelial layer of the anterior-
      and posteriormost portions of the digestive tract. In adult, its expression was
      limited to the surface layer of stratified epithelial tissues, including skin
      epidermis and epithelia of mouth, pharynx, esophagus, and rectum but not in the
      gastral and intestinal epithelia. By using a 2.2-kb promoter from krt8, several
      stable green fluorescent protein (gfp) transgenic zebrafish lines were
      established. All of these transgenic lines displayed GFP expression in tissues
      mentioned above except for the rectum; therefore, the pattern of transgenic GFP
      expression is essentially identical to that of the endogenous krt8 mRNAs. krt8
      GFP fusion protein was also expressed in zebrafish embryos under a ubiquitous
      promoter, and the fusion protein was capable of assembling into intermediate
      filaments only in the epithelia that normally expressed krt8 mRNAs, indicating
      the specificity of keratin assembly in vivo.

PMID- 11836786
TI  - Docking protein SNT1 is a critical mediator of fibroblast growth factor signaling
      during Xenopus embryonic development.
AB  - The docking protein SNT1/FRS2 (fibroblast growth factor receptor substrate 2) is
      implicated in the transmission of extracellular signals from several growth
      factor receptors to the mitogen-activated protein (MAP) kinase signaling cascade,
      but its biological function during development is not well characterized. Here,
      we show that the Xenopus homolog of mammalian SNT1/FRS-2 (XSNT1) plays a critical
      role in the appropriate formation of mesoderm-derived tissue during
      embryogenesis. XSNT1 has an expression pattern that is quite similar to the
      fibroblast growth factor receptor-1 (FGFR1) during Xenopus development. Ectopic
      expression of XSNT1 markedly enhanced the embryonic defects induced by an
      activated FGF receptor, and increased the MAP kinase activity as well as the
      expression of a mesodermal marker in response to FGF receptor signaling. A loss
      of-function study using antisense XSNT1 morpholino oligonucleotides (XSNT-AS)
      shows severe malformation of trunk and posterior structures. Moreover, XSNT-AS
      disrupts muscle and notochord formation, and inhibits FGFR-induced MAP kinase
      activation. In ectodermal explants, XSNT-AS blocks FGFR-mediated induction of
      mesoderm and the accompanying elongation movements. Our results indicate that
      XSNT1 is a critical mediator of FGF signaling and is required for early Xenopus
      development.

PMID- 11836787
TI  - Gamma-tubulin in chicken erythrocytes: changes in localization during cell
      differentiation and characterization of cytoplasmic complexes.
AB  - The mechanism of marginal band (MB) formation in differentiating erythroid cells
      is not fully understood, and the proteins involved in nucleation of MB
      microtubules are largely unknown. To gain insights into the function of gamma
      tubulin in MB formation, we have followed its distribution in developing chicken
      erythrocytes and characterized soluble forms of the protein. In early stages of
      erythroid cells differentiation, gamma-tubulin was present in microtubule
      organizing centers, mitotic spindles, as well as on MB. Its subcellular
      localization changed in the course of differentiation, and in postnatal
      peripheral erythrocytes gamma-tubulin was found only in soluble forms. After cold
      induced depolymerization gamma-tubulin in erythroid cells formed large clusters
      that were not observed in matured cells, and re-growth experiments demonstrated
      that gamma-tubulin was not present in distinct nucleation structures at the cell
      periphery. Soluble gamma-tubulin formed complexes of various size and large
      complexes were prone to dissociation in the presence of high salt concentration.
      Interaction of gamma-tubulin with tubulin dimers was revealed by precipitation
      experiments. gamma-Tubulin occurred in multiple charge variants whose number
      increased in the course of erythrocyte differentiation and corresponded with
      decreased binding to MB. The presented data demonstrate for the first time that
      gamma-tubulin is a substrate for developmentally regulated posttranslational
      modifications and that the binding properties of gamma-tubulin or its complexes
      change during differentiation events.

PMID- 11836788
TI  - Frizzled-7 and limb mesenchymal chondrogenesis: effect of misexpression and
      involvement of N-cadherin.
AB  - Products of the Frizzled family of tissue polarity genes have been identified as
      putative receptors for the Wnt family of signaling molecules. Wnt-signaling is
      implicated in the regulation of limb mesenchymal chondrogenesis, and our recent
      study indicates that N-cadherin and related activities are functionally involved
      in Wnt-7a-mediated inhibition of chondrogenesis. By using an in vitro high
      density micromass culture system of chick limb mesenchymal cells, we have
      analyzed the spatiotemporal expression patterns and the effects on chondrogenesis
      of RCAS retroviral-mediated misexpression of Chfz-1 and Chfz-7, two Frizzled
      genes implicated in chondrogenic regulation. Chfz-1 expression was localized at
      areas surrounding the cartilaginous nodules at all time points examined, whereas
      Chfz-7 expression was limited to cellular aggregates during initial mesenchymal
      condensation, and subsequently was down-regulated from the centers toward the
      periphery of cartilage nodules at the time of chondrogenic differentiation,
      resembling the pattern of N-cadherin expression. Chondrogenesis in vitro was
      inhibited and limited to a smaller area of the culture upon misexpression of Chfz
      7, but not affected by Chfz-1 misexpression. Analyses of cellular condensation
      and chondrogenic differentiation showed that the inhibitory action of Chfz-7 is
      unlikely to be at the chondrogenic differentiation step, but instead affects the
      earlier precartilage aggregate formation event. At 24 hr, expression of N
      cadherin, a key component of the cellular condensation phase of chondrogenesis,
      was delayed/suppressed in Chfz-7 misexpressing cultures, and was limited to a
      significantly smaller cellular condensation area within the entire culture at 48
      hr, when compared with control cultures. Chfz-1 misexpressing cultures appeared
      similar to control cultures at all time points. However, neither Chfz-1 nor Chfz
      7 misexpression affected mesenchymal cell proliferation in vitro. These results
      suggest that Chfz-7 is active in regulating N-cadherin expression during the
      process of limb mesenchymal chondrogenesis and that Chfz-1 and Chfz-7 are
      involved in different Wnt-signaling pathways.

PMID- 11836789
TI  - Two Na,K-ATPase beta 2 subunit isoforms are differentially expressed within the
      central nervous system and sensory organs during zebrafish embryogenesis.
AB  - We have identified cDNAs encoding a second zebrafish ortholog of the human Na,K
      ATPase beta 2 subunit. The beta 2b cDNA encodes a 292 amino acid-long polypeptide
      with 74% identity to the previously characterized zebrafish beta 2a subunit. By
      using a zebrafish meiotic mapping panel, we determined that the beta 2b gene
      (atp1b2b) was tightly linked to markers on linkage group 5, whereas the beta 2a
      gene was located on linkage group 23. In situ hybridization analysis shows that
      in developing zebrafish embryos, atp1b2a and atp1b2b are predominantly expressed
      in the nervous system. beta 2a transcripts were abundantly expressed throughout
      brain as well as spinal cord neurons and lateral line ganglia. In contrast, beta
      2b mRNA expression was primarily detected in sensory organs, including retina,
      otic vesicles, and lateral line neuromast cells. These results suggest that the
      beta 2a and beta 2b genes play distinct roles in developing brain and sensory
      organs, and raise the possibility that the functions encoded by the single
      mammalian beta 2 gene may be partitioned between the two zebrafish beta 2
      orthologs.

PMID- 11836790
TI  - Cell proliferation during blastema formation in the regenerating teleost fin.
AB  - Epimorphic regeneration in teleost fins occurs through the establishment of a
      balanced growth state in which a blastema gives rise to all the mesenchymal
      cells, whereas definite areas of the epidermis proliferate leading to its
      extension, thus, allowing the enlargement of the whole structure. This type of
      regeneration involves specific mechanisms that temporally and spatially regulate
      cell proliferation. To understand how the blastema is formed and how this growth
      situation is set up, we investigated cell proliferation patterns in the
      regenerating fin of the goldfish Carassius auratus from the time of amputation to
      that of blastema formation by using proliferating cell nuclear antigen
      immunostaining and bromodeoxyuridine labeling. Wound closure and apical epidermal
      cap formation took place by epidermal migration and re-arrangement, without the
      contribution of cell proliferation. As soon as the apical cap had formed, the
      epidermis started to proliferate at its lateral surfaces, in which all layers
      maintained cycling for the duration of the studied process. The distal epidermal
      cap, on the contrary, presented very few cycling cells, and its cytoarchitecture
      was indicative of continuous remodeling due to ray growth. The basal layer of
      this epidermal cap showed a typical morphology and remained nonproliferative
      whilst in contact with the proliferating blastema. Proliferation in the
      mesenchymal compartment of the ray started far from the amputation plane.
      Subsequently, cycling cells approached that location, until they formed the
      blastema in contact with the apical epidermal cap. Differences observed between
      the epidermis and mesenchyma, regarding activation of the cell cycle and the
      establishment of proliferative patterns, suggest that differential mechanisms
      regulate cell proliferation in each of these compartments during the initial
      stages of regeneration.

PMID- 11836791
TI  - Role for alpha 6 integrin during lens development: Evidence for signaling through
      IGF-1R and ERK.
AB  - We show that alpha 6 integrin function was required for normal lens cell
      differentiation by using an antisense construct to suppress alpha 6 integrin
      expression. To elucidate the mechanism by which this integrin functions in the
      regulation of the lens cell differentiation process, we determined the molecular
      composition of alpha 6 integrin signaling complexes at distinct stages of
      differentiation in vivo. Because both alpha 6 integrin and insulin-like growth
      factor-1 (IGF-1) have been implicated in signaling lens cell differentiation, we
      examined the possibility that they formed a signaling complex in the embryonic
      lens. Coprecipitation analysis revealed that alpha 6 integrin/IGF-1 receptor
      complexes were present and that their association was greatest in the equatorial
      zone, the region of the embryonic lens in which lens cells proliferate and then
      initiate their differentiation. These results provide in vivo support for the
      formation of integrin/growth factor receptor signaling complexes. We also found
      that extracellular signal-regulated kinase (ERK), a downstream effector of both
      integrin and growth factor receptor signaling pathways, was associated with the
      alpha 6 integrin signaling complexes in the embryonic lens. This result was
      supported by our findings that activated ERK, in addition to its nuclear
      location, localized to lens cell membranes in specific regions of cell-matrix and
      cell-cell contact. A connection between integrin ligand engagement and ERK
      activation was shown in vitro after lens cell attachment to laminin. These
      results demonstrate that alpha 6 integrin function is required for the early
      stages of lens cell differentiation most likely through its association with the
      IGF-1 receptor and the activation of ERK.

PMID- 11836792
TI  - A critical period for functional vestibular development in zebrafish.
AB  - We have determined a critical period for vestibular development in zebrafish by
      using a bioreactor designed by NASA to simulate microgravity for cells in
      culture. A critical period is defined as the briefest period of time during
      development when stimulus deprivation results in long lasting or permanent
      sensory deficits. Zebrafish eggs were collected within 3 hours of being laid and
      fertilized. In experiment 1, eggs were placed in the bioreactor at 3, 24, 30, 36,
      48, or 72 hours postfertilization (hPF) and maintained in the bioreactor until 96
      hPF. In experiment 2, eggs were placed in the bioreactor immediately after they
      were collected and maintained in the bioreactor until 24, 36, 48, 60, 66, 72, or
      96 hPF. Beginning at 96 hPF, all larvae had their vestibulo-ocular reflexes (VOR)
      evaluated once each day for 5 days. Only larvae that hatched from eggs that were
      placed in the bioreactor before 30 hPF in experiment 1 or removed from the
      bioreactor later than 66 hPF in experiment 2 had VOR deficits that persisted for
      at least 5 days. These data suggest a critical period for vestibular development
      in the zebrafish that begins before 30 hPF and ends after 66 hPF. To confirm
      this, zebrafish eggs were placed in the bioreactor at 24 hPF and removed at 72
      hPF. VORs were evaluated in these larvae once each day for 5 days beginning at 96
      hPF. These larvae had VOR deficits that persisted for at least 5 days. In
      addition, larvae that had been maintained in the bioreactor from 24 to 66 hPF or
      from 30 to 72 hPF, had only temporary VOR deficits. In a final experiment,
      zebrafish eggs were placed in the bioreactor at 3 hPF and removed at 96 hPF but
      the bioreactor was turned off from 24 hPF to 72 hPF. These larvae had normal VORs
      when they were removed from the bioreactor at 96 hPF. Taken as a whole, these
      data support the idea that there is a critical period for functional maturation
      of the zebrafish vestibular system. The developmental period identified includes
      the timeframe during which the vestibular primary afferent neurons are born,
      innervate their central and peripheral targets, and remodel their central
      projections.

PMID- 11836793
TI  - Eye defects in receptor protein-tyrosine phosphatase alpha knock-down zebrafish.
AB  - Receptor protein-tyrosine phosphatase alpha (RPTP alpha) is highly expressed in
      the developing retina of different species, but little is known about its
      function there. Here, we report that injection of antisense morpholinos in
      zebrafish embryos reduced RPTP alpha expression to almost nondetectable levels up
      to 3 days postfertilization (dpf). RPTP alpha was detectable again from 4 dpf
      onward. RPTP alpha knock-down resulted in smaller eyes. Examination of sections
      of the retina at different developmental stages demonstrated that already at 28
      hours postfertilization (hpf) fewer cells were present in the retina of RPTP
      alpha-morpholino-injected embryos. At 3 dpf, the layered organization of the
      retina was absent. In addition, the morphology and labeling with an axon specific
      antibody, acetylated tubulin, demonstrated that most cells appeared to be
      undifferentiated. Strikingly, at 5 dpf the lamination of the retina was partially
      restored, concomitant with re-expression of RPTP alpha protein. Although cells in
      the retina were now differentiated, the layering of the retina remained disrupted
      and significant gaps were observed in the amacrine cell layer. Therefore, knock
      down of RPTP alpha protein provides evidence that RPTP alpha is essential for
      normal retinal development.

PMID- 11836795
TI  - Determinants of bronchial responsiveness to methacholine at school age in twin
      pairs.
AB  - The methacholine inhalation challenge test (MIC) was used to evaluate bronchial
      responsiveness in 67 children who were the products of multiple pregnancies when
      they were 7-15 years old. At birth, 30 (45%) infants had intrauterine growth
      retardation (IUGR; birth weight <2 SD below normal birth weight, or birth weight
      difference >1.3 SD between twin-pairs), and 59 (88%) were born before 37 weeks of
      gestation. None of the children had doctor-diagnosed asthma. The provocative dose
      of methacholine causing a 20% fall in Wright's peak expiratory flow (WPEF) (PD20)
      was below 1,000 microg in 10 (15%) children, and they were classified as MIC
      responders. There were no differences in perinatal or neonatal factors between
      MIC responders and nonresponders; in particular, MIC responses did not differ
      between IUGR infants, and children with appropriate growth for gestational age
      (AGA) at birth. There were seven discordant pairs in which one child was a MIC
      responder and the other was not; 5 responders were IUGR, and 2 were AGA children
      (ns). Respiratory tract infections after the neonatal period were equally common
      in IUGR and AGA children. However, these infections were associated with later
      bronchial hyperresponsiveness. Doctor-diagnosed respiratory infections, numbers
      of antibiotic courses, episodes of otitis media, and the need for adenoidectomy,
      tonsillectomy, and tympanostomy were more common in MIC responders than in
      nonresponders. We conclude that IUGR was not associated with subsequent bronchial
      hyperresponsiveness in twin pairs assessed by the MIC test. A significant
      relationship was seen between bronchial hyperresponsiveness and infections after
      the neonatal period.

PMID- 11836794
TI  - Zebrafish yolk-specific not really started (nrs) gene is a vertebrate homolog of
      the Drosophila spinster gene and is essential for embryogenesis.
AB  - By using retroviral insertional mutagenesis in zebrafish, we have identified a
      recessive lethal mutation in the not really started (nrs) gene. The nrs mutation
      disrupts a gene located in linkage group 3 that is highly homologous to the
      spinster gene identified in Drosophila and to spinster orthologs identified in
      mammals. In flies, spinster encodes a membrane protein involved in lysosomal
      metabolism and programmed cell death in the central nervous system and in the
      ovary. In nrs mutant fish embryos, we detect an opaque substance in the posterior
      yolk cell extension at approximately 1 day after fertilization. This material
      progressively accumulates and by 48 hr after fertilization fills the entire yolk.
      By day 3 of embryogenesis, mutant embryos are severely reduced in size compared
      with their wild-type siblings and they die a few hours later. By in situ
      hybridization, we show that the nrs mRNA is expressed in the yolk cell at the
      time the mutant phenotype becomes apparent. In wild-type embryos, nrs message is
      present maternally and zygotically throughout embryogenesis and is also detected
      in adult animals. In nrs homozygous mutant embryos, nrs transcripts are
      undetectable at the time the phenotype becomes apparent, indicating that the
      retroviral insertion has most likely abolished expression of the nrs gene.
      Finally, the nrs phenotype can be partially rescued by microinjection of nrs
      encoding DNA. These results suggest that the nrs mutation affects an essential
      gene encoding a putative membrane-bound protein expressed specifically in the
      yolk cell during zebrafish embryogenesis.

PMID- 11836796
TI  - Nasal airflow and resistance measured by active anterior rhinomanometry in
      healthy children and adolescents.
AB  - Rhinomanometry allows objective assessment of nasal patency in pediatric patients
      with nasal and other respiratory problems. However, no reliable reference values
      are available in the pediatric age group. We measured nasal inspiratory airflow
      and nasal inspiratory resistance of the right and left nostrils (V'nar, V'nal,
      Rnar, and Rnal) and total nasal inspiratory flow and resistance (V'na and Rna) at
      a transnasal pressure of 150 Pa during quiet breathing in healthy children with a
      closed mouth by using active anterior rhinomanometry. Cross-sectional
      measurements were done in 192 healthy Caucasian children and adolescents free of
      nasal or other respiratory diseases (age, 2-19 years; body height, 94-190 cm; 95
      boys and 97 girls). The values of V'na, V'nar, and V'nal increased significantly
      with an increase of body height or age (P<0.0001). Rna, Rnar, and Rnal
      significantly decreased with an increase of body height and age (P<0.0001). No
      significant statistical differences were found between boys and girls (P=0.11) or
      between right and left nostrils (P=0.07). V'nar and Rnar comprised 50.1%, and
      V'nal and Rnal 49.9%, of total V'na and Rna, respectively. Best-fit regression
      equations relating rhinomanometric parameters and body height or age were power
      functions. We obtained reference regression equations with upper and lower
      limits, and prepared tables listing reference (normal) values of rhinomanometric
      parameters in healthy pediatric Caucasian patients, against which patients with
      nasal obstruction can be compared.

PMID- 11836799
TI  - Randomized controlled study of in-hospital exercise training programs in children
      with cystic fibrosis.
AB  - The aim of this study was to compare aerobic and resistance training in children
      with cystic fibrosis (CF) admitted to hospital with an intercurrent pulmonary
      infection with a control group. The subjects were randomized into three groups on
      the first day of admission. The fat-free mass (FFM) was calculated, using the
      skin fold thickness from four sites (biceps, triceps, subscapular, and iliac
      crest). Pulmonary function tests were performed within 36 hr of admission and
      repeated on discharge from the hospital, and again at 1 month after discharge.
      All subjects performed an incremental treadmill exercise test, using a modified
      Bruce protocol. Lower limb strength was measured using a Cybex dynamometer. An
      assessment of quality of life was made using the Quality of Well Being Scale, as
      previously reported. Activity levels were measured using a 7-day activity diary,
      and subjects also wore an accelerometer on their hips. There were no significant
      differences between the three groups in terms of disease severity, and length of
      stay in hospital. Subjects in all three groups received intravenous antibiotics
      and nutritional supplementation as determined by the physician. Children
      randomized to the aerobic training group participated in aerobic activities for
      five sessions, each of 30-min duration, a week. The children randomized to the
      resistance training group exercised both upper and lower limbs against a graded
      resistance machine. Subjects in the control group received standard chest
      physiotherapy. Our study demonstrated that children who received aerobic training
      had significantly better peak aerobic capacity, activity levels, and quality of
      life than children who received the resistance training program. Children who
      received resistance training had better weight gain (total mass, as well as fat
      free mass), lung function, and leg strength than children who received aerobic
      training. A combination of aerobic and resistance training may be the best
      training program, and future studies to assess optimal training programs for CF
      patients are indicated.

PMID- 11836801
TI  - Safety of inhaled corticosteroids in children.
AB  - Inhaled corticosteroids (ICS) are now first-line therapy for persistent asthma in
      children. The major safety concerns of long-term ICS therapy for childhood asthma
      are potential effects on adrenal function, growth, and bone mass. Dosage, type of
      inhaler device, and individual drug characteristics influence systemic effects of
      ICS. Sensitive measures of basal adrenal function can show statistically
      significant changes during ICS therapy, but these do not accurately predict
      clinically meaningful adrenal axis suppression. Adrenal insufficiency is rare and
      confined to children receiving high doses of ICS. Dose-related inhibition of
      growth has been seen in some short- and intermediate-term studies, but long-term
      studies have found no detrimental effect on final height. ICS therapy has not
      been associated with significant changes in measurements of bone and bone
      biomarkers, but more studies of high doses and of therapy in adolescents are
      needed. Overall, although ICS are the most effective anti-inflammatory treatment
      available for asthma, high doses of ICS in children are still of concern. The
      risk of high doses is compounded in children with concomitant allergic conditions
      that require multiple forms of topical corticosteroids. Benefits of ICS clearly
      outweigh potential adverse effects and risks associated with poorly controlled
      asthma. Risk can be minimized by using the lowest effective ICS dose, limiting
      systemic availability of the drug through proper technique to minimize swallowed
      drug, and selection of agents with efficient first-path hepatic inactivation of
      swallowed drug. Adjuvant treatments can reduce the dose of ICS required for
      asthma control, allowing a reduction in overall systemic exposure for most
      children with mild-to-moderate persistent asthma. Therefore, these agents should
      be added to, but should not replace, ICS therapy.

PMID- 11836798
TI  - Salbutamol dry powder inhaler: efficacy, tolerability, and acceptability study.
AB  - Dry powder inhaler (DPI) devices are frequently used in children over 5 years of
      age in order to avoid coordination difficulties often seen with the use of
      pressurized metered dose inhalers (pMDI). This study assessed the efficacy,
      tolerability, and acceptability of salbutamol delivered via two delivery systems,
      in a population of pediatric patients. The primary aim of the study was to
      investigate the bronchodilator efficacy of a single dose (100 microg) of
      salbutamol administered via a dry powder inhaler (Clickhaler) compared to a
      similar dose administered by a pressurized metered dose inhaler via a large
      valved holding chamber (VHC) to children with asthma. The study comprised two
      phases: the first comparator phase, followed by an open 4-week treatment period.
      Sixty-one children with a mean (SD) age of 11.3 years (2.9) (range, 6-17) and
      mild or moderate asthma completed the study. The primary efficacy endpoint,
      forced expiratory volume in 1 sec (FEV1), indicated that there was no clinically
      or statistically significant difference between the bronchodilator effects of
      salbutamol delivered via either device, with a maximum posttreatment percentage
      change in FEV1 (SD) of 12.4% (10.0) and 14.15 (9.3) for Clickhaler and pMDI plus
      VHC, respectively. Most patients rated the Clickhaler as easy to use (97%) and
      liked the device (84%). Both treatments were well--tolerated. These results
      support the suitability of salbutamol Clickhaler as an acceptable, well
      tolerated, and effective alternative to a pMDI plus VHC in mild to moderate
      asthmatic children over age 6 years.

PMID- 11836800
TI  - Mannose-binding lectin (MBL) therapy in an MBL-deficient patient with severe
      cystic fibrosis lung disease.
AB  - Deficiency of mannose-binding lectin has been shown to be a risk factor for
      cystic fibrosis (CF) patients. We, therefore, decided to treat a patient with CF,
      mannose-binding lectin deficiency, severe bronchopulmonary Pseudomonas aeruginosa
      infection, and rapid deterioration of lung function with purified mannose-binding
      lectin in an attempt to ameliorate the course of the lung disease. The mannose
      binding lectin used originated from pooled human donor plasma and was given as an
      intravenous infusion twice a week for a period of 3 months. The patients's
      clinical condition was stabilized during the treatment period, but was not
      improved. No adverse events were observed. However, the lung function assessed as
      percent forced expiratory volume in 1 sec (FEV1%) and percent forced vital
      capacirt (FVC%) correlated significantly with the mannose-binding serum lectin
      levels (rho=+0.68, P=0.008, and rho=+0.73, P=0.004). Additionally, an inverse
      correlation with the acute phase-reactant C-reactive protein and the
      proinflammatory cytokine IL-6 was observed (rho=-0.49, P=0.007 and rho=-0.41,
      P=0.04, respectively). The results emphasize the importance of mannose-binding
      lectin as a secondary disease modifier in CF. Moreover, purified mannose-binding
      lectin can safely be administered to chronically ill patients, and may be a
      potential treatment in CF and other diseases in which mannose-binding lectin
      deficiency plays a pathophysiological role.

PMID- 11836802
TI  - Successful treatment of methicillin-resistant Staphylococcus aureus pulmonary
      infection with linezolid in a patient with cystic fibrosis.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is a significant cause of
      pulmonary infection in patients with cystic fibrosis (CF). Because these
      organisms are frequently multidrug-resistant, most patients require intravenous
      therapy with vancomycin. We report on the first case of successful treatment of a
      pulmonary exacerbation due to MRSA in a CF patient with a new antimicrobial,
      linezolid. We demonstrated equivalence of intravenous and oral dosing in this
      patient, suggesting that oral linezolid may be an excellent alternative to
      intravenous vancomycin for CF patients infected with MRSA.

PMID- 11836797
TI  - Pulmonary function in technology-dependent children 2 years and older with
      bronchopulmonary dysplasia.
AB  - Somatic and pulmonary growth coincide with resolution of hypoxemia by 2 years of
      age in most children with bronchopulmonary dysplasia (BPD). However, a distinct
      subgroup of children with BPD continue to require mechanical ventilation and/or
      supplemental oxygen beyond 2 years of age. This study tested the hypothesis that
      indices of pulmonary function would be significantly worse in children with BPD 2
      years and older who remained technology-dependent secondary to hypoxemia,
      compared to those of age-matched children with BPD who were normoxemic. We
      measured pulmonary mechanics in 21 oxygen- or ventilator-dependent children with
      BPD 2 years and older (BPDO2 group; mean age+/-SD, 30.2+/-6.5 months) and in 19
      children with BPD who had been weaned off mechanical ventilation and supplemental
      oxygen for at least 6 months (control group; mean age, 30.1+/-5.5 months).
      Respiratory rate and tidal volume were measured after sedation with chloral
      hydrate, and dynamic compliance and expiratory conductance were calculated using
      the esophageal catheter technique. Maximal flow at FRC (V'(maxFRC)) and ratio of
      forced-to-tidal flows at midtidal volume were obtained by the rapid thoracic
      compression technique. FRC was determined by nitrogen washout. There were no
      statistically significant differences in most measured indices of pulmonary
      mechanics between the BPDO2 and control groups. However, V'(maxFRC)/FRC was
      higher in controls compared to subjects in the BPDO2 group (0.81+/-0.40 sec(-1)
      vs. 0.34+/-0.21 sec(-1), P<0.003). We conclude that most indices of pulmonary
      function in children with BPD 2 years and older do not reflect the need for
      mechanical ventilation or supplemental oxygen. We speculate that measurements of
      lung elastic recoil and tests of distribution of ventilation and pulmonary
      perfusion may be more sensitive in differentiating normoxemic and hypoxemic
      children with BPD 2 years and older.

PMID- 11836803
TI  - Laryngeal hirudiniasis: an unusual cause of airway obstruction and hemoptysis.
AB  - Cases of childhood hemoptysis are rare and usually result from foreign body
      aspiration or congenital heart or lung diseases. However, human hirudiniasis due
      to the leech still exists, and could involve the upper airways after drinking
      infested water from quiet streams and pools. We report the case of a 6-year-old
      child who presented suffocating at the emergency room after having been
      misdiagnosed and treated for asthma over a 1-month period. His mother reported he
      had had recurrent hemoptysis, as well. The child inadvertently drank leech
      infested water in a rural area of northern Syria. Surgical removal of the leech
      resulted in prompt resolution of the symptoms. Although laryngeal hirudiniasis is
      rare in the developed world, it remains a possible cause of childhood airway
      obstruction, hemoptysis, and anemia which needs to be considered in patients with
      a suggestive history.

PMID- 11836805
TI  - To the editor: Is it safe to administer a continuous infusion of ceftazidime
      (Fortum) prepared for 24 hours in cystic fibrosis (CF) patients?

PMID- 11836804
TI  - Selective fiberoptic left main-stem intubation for severe unilateral barotrauma
      in a 24-week premature infant.
AB  - A 24-week premature infant developed severe right-sided pulmonary barotrauma
      secondary to mechanical ventilation for respiratory distress syndrome (RDS). High
      frequency oscillatory ventilation and permissive hypercapnia were initiated. A
      chest tube was placed to relieve a pneumothorax, and a catheter was inserted into
      an air-filled cyst for drainage. These maneuvers failed to improve the child's
      respiratory status. The child's left main-stem bronchus was then successfully
      fiberoptically intubated for single-lung ventilation in order to reduce the
      unilateral barotrauma. Single-lung ventilation was effectively and safely
      continued for 5 days, with complete resolution of the pulmonary barotrauma.

PMID- 11836807
TI  - [Forensic odontology. Introduction].
AB  - Human teeth and dental restorations have proven to remain stable during a long
      time as well as in extreme situations such as fire. Therefore, forensic
      odontology can play an important part in the identification of severe mutilated
      bodies of unknown persons. The essence of the identification procedure is
      comparing the post mortem remains with the ante mortem records. In this issue
      several authors describe the importance of forensic odontology by means of the
      use of dental records in mass disasters. Another aspect of forensic odontology is
      the examination of bite marks, which can be seen in some criminal cases.

PMID- 11836808
TI  - [Forensic odontology within the Disaster Victim Identification team of the Dutch
      Police Force].
AB  - The author participated as a forensic odontologist in the Dutch Disaster Victim
      Identification (DVI-)team during the period 1977-1995. In this article he
      describes the organization and procedure of this police unit, which is especially
      trained for the recovery and identification of victims. He also gives an
      impression of the organization and the special manner of identification of the
      forensic odontologists within the group of external specialists of the DVI-team.
      He describes the technical aspects of the identification activities of the
      forensic odontologists, as well as the identification problems at different sorts
      of mass disasters. The quality of the records obtained from the victims' dentists
      greatly influences the final results of dental identification.

PMID- 11836809
TI  - [Bite mark analysis. Part 1. Methods and overview].
AB  - Criminal cases in which a suspect or a victim has left his or her teeth marks on
      another person or on an inanimate object such as a candy bar, an apple, cheese or
      even a beer can seem to occur more frequently. Testifying to the similarity or
      dissimilarity of a suspect's dentition to the bite mark in question is probably
      the most unique contribution that forensic dentistry makes to the judicial
      inquiry. This is a grave responsibility because a defendant's life or freedom may
      depend on the testimony given by the forensic odontologist in court.

PMID- 11836810
TI  - [Bite mark analysis. Part 2. A selection of Dutch cases].
AB  - This contribution reflects the author's experiences with three selected bite mark
      analyses. One case concerns a bite mark found on mortal remains, one found on a
      living person and one found on food.

PMID- 11836806
TI  - To the editor: Bronchoalveolar lavage (BAL) in pediatric cystic fibrosis (CF):
      its clinical use modified by audit in a regional CF center.

PMID- 11836811
TI  - [Confidential information in forensic odontologic investigation].
AB  - The forensic odontologist is normally not bound by any professional secrecy
      during his forensic investigation. He has to present the legal authorities with
      all details of his findings. But he has to respect the rights of the defense and
      the human rights. He cannot force a suspect to undergo any examination without
      his explicit and informed consent. Dental records are covered by confidentiality
      and shall not be handed out to the forensic odontologist without the patient's
      consent.

PMID- 11836812
TI  - [The Tenerife disaster].
AB  - In this article some comments are made about the dental identification-work
      during the Tenerife-air disaster in 1977. This disaster caused the death of 335
      Americans and 248 Dutchmen of which 80% could be identified. The dentitions
      seemed to be one of the most important criteria for identification. Forensic
      odontology should follow standard procedures and general practitioners should
      anticipate on their part in supplying antemortal data.

PMID- 11836813
TI  - [Forensic odontologic activities across borders].
AB  - During the past twenty years the author has examined a large number of human
      bodies, recovered from the Dutch rivers in the area Arnhem-Nijmegen. The aim of
      the examinations was to identify the bodies by means of the human dentition.
      Attention is drawn to the typical characteristics, attached to human bodies
      recovered from floating waterways in general and to human bodies originating from
      the neighbouring country Germany and being recovered in the Netherlands in
      particular.

PMID- 11836814
TI  - [Forensic odontological identification of disaster victims. Experience with the
      disaster of the Martinair DC-10 in Faro, Portugal].
AB  - Forensic odontology plays an important, often decisive role in the identification
      of disaster victims. In the Dutch situation, the forensic odontologist is part of
      the Disaster Victim Identification (DVI)-team of the Dutch National Police Force.
      The extensive experience with forensic odontological identification of disaster
      victims, gained within the Dutch DVI-team is described and illustrated with
      reference to the identification procedure following the Martinair DC-10 aircraft
      crash at Faro, Portugal, december 21st, 1992. In the identification of the total
      of 56 victims, forensic odontology contributed in 55 cases (98.2%) to the
      identification; in 40 cases there were such clear agreements that identification
      based on forensic odontology alone would have been sufficient. The success of the
      forensic odontological identification method appeared to be greatly dependent of
      the adequate cooperation of dentists that made their treatment data available for
      comparison.

PMID- 11836815
TI  - [100 years of x-rays: increase in image quality of intra-oral radiographs,
      decrease in patient exposure].
AB  - Comparing a present-day bitewing radiograph with one of the first dental
      radiographs made immediately after the discovery of the X-rays, we can see how
      enormously the image quality of dental radiographs has improved. Besides the
      improved image quality, patient exposure has decreased considerably during the
      past 100 years. Improvement of image quality and reduction of patient exposure
      have been brought about by changes of X-ray equipment and radiographic films.
      These changes, which have led to a better image quality and a decrease of patient
      exposure during the past 100 years, are discussed in this article.

PMID- 11836816
TI  - [The effect of expertise on the interpretation of dental radiographic images].
AB  - A difference exists in the way novices and experts interpret dental radiographs.
      For education in dental radiology knowledge about the expert strategy is
      important. The aim of this study was to determine how novices and experts differ
      in the way they judge dental radiographs. Therefore 16 radiographs with different
      types of pathologies in the hard tissues were observed by 15 observers with three
      different levels of expertise. Based on their verbal reports the information
      content of the radiographs was determined for the different expertise levels. One
      radiograph with the same information content for all levels was observed by 8
      novices and 8 experts. The eye movements of the observers were registered during
      the interpretation. Based on the results it is concluded that the experts make a
      more adequate selection of the stimulus material. Recommendations are given for
      the structure of the educational programme in dental radiology.

PMID- 11836819
TI  - [Bitewing radiographs in dentistry: how frequently are they indicated?].
AB  - Bitewing radiographs should be taken on an individual indication. The
      individual's caries risk is an important factor in determining the frequency of
      bitewing radiographs and, therefore, a dentist should estimate the individual's
      caries risk. Given two serial bitewing radiographs, the dentist should be able to
      distinguish freshly developed caries lesions, which require preventive or
      restorative treatment, from old remineralized lesions, which do not require any
      treatment at all. Assessment of caries progression from serial bitewing
      radiographs should also provide the dentist with information to determine the
      moment of subsequent bitewing radiographs. Because in many western countries the
      caries prevalence is quite low, this is a complicated task, since the dentist is
      expected to carry out the diagnostic and decision making process without errors.
      The true probability of caries progression was derived and plotted as a function
      of the time span between two bitewing radiographs. The results indicated that the
      interval between standardized serial bitewing radiographs should be approximately
      three years for individuals which run a high risk of developing caries, and four
      years for individuals with a low caries risk.

PMID- 11836818
TI  - [Radiation risks in dental and medical radiography].
AB  - Biological effects of exposure to ionizing radiation in diagnostic dental and
      medical radiology are stochastic effects such as carcinogenesis and genetical
      effects. Today, radiation exposure due to an x-ray or nuclear medicine
      examination varies from less then 0.001 mSv to more then 10 mSv effective dose.
      The background level of natural radiation in the Netherlands is about 2 mSv.
      Assuming that an appropriate indication for the examination exists, it can be
      stated that generally the diagnostic information obtained outweighs by far the
      risks involved in the exposure to radiation.

PMID- 11836820
TI  - [Application of tomography to dentistry].
AB  - The conventional radiograph is the 2D-projection of a 3D-object. Therefore,
      information about the third dimension is missing. Various x-ray techniques are
      available to obtain information about the third dimension. Depending on the
      diagnostic purpose, global information can be obtained by a second radiograph
      taken with a different angulation (for instance, to localize an impacted tooth).
      However, sometimes more detailed information is required about the spatial
      relationship (for instance, when determining the amount of bone mass in implant
      planning). CT and MRI are the most appropriate techniques when complete volume
      information is required. In the near future, tomosynthesis and microCT will
      become available to obtain detailed 3D-information for dental applications.

PMID- 11836817
TI  - [Quality control of intra-oral radiographs].
AB  - This paper deals with the different stages in the process of making intra-oral
      radiographs and the factors which influence their quality: the X-ray equipment,
      operator technique, and processing and film variables. Common errors at each
      stage are discussed and suggestions for quality assurance measures are given.

PMID- 11836822
TI  - [Conformational radiotherapy in cancer of the head and neck: a future
      perspective].
AB  - The discovery of X-rays in 1895 by Wilhelm Conrad Rontgen paved the way to a new
      scientific epoch in the management of cancer. Today, with the XXI century in
      sight, radiotherapy has matured and has become one of the mainstays in the
      management of cancer. Although long-term success with the use of ionizing
      radiation in cancer treatment can be achieved in about half of our patients,
      significant improvements in tumor control rates and/or reduction in side effects
      (i.e. quality of life) are needed. As a future perspective, the authors highlight
      the gains that can be anticipated from research in the field of 3-D conformal
      radiotherapy, in particular with regard to sparing critical structures (e.g.
      parotid glands) in cancers of the head & neck.

PMID- 11836821
TI  - [Are conventional dental x-ray films a thing of the past?].
AB  - Dental x-ray film is still the most important medium for the detection and
      storage of x-ray images. However, just as the use of computers cannot be stopped,
      digital techniques will take over the role of dental x-ray films in dental
      radiology.

PMID- 11836824
TI  - CNA's are recognized.

PMID- 11836825
TI  - Attitude adjustment remedy: reassess your thought process.

PMID- 11836826
TI  - Abuse of residents is a major problem in U.S. nursing homes.

PMID- 11836828
TI  - Clinical practice guideline: screening and diagnosing autism.
AB  - The clinical practice guideline (CPG) reviewed in this month's column concerns
      the screening and diagnosis of autism. Autism is the third most common
      developmental disability and affects more than 1 in 500 children, or nearly
      400,000 people in the United States, in some form. Primary care providers of
      children, including pediatric nurse practitioners (PNPs) and family nurse
      practitioners (FNPs), should reasonably expect to care for at least one child
      with autism (CWA). The American Academy of Neurology (AAN) has therefore
      developed guidelines to help healthcare providers facilitate the early
      identification of children with autism.

PMID- 11836827
TI  - Infectious diseases of refugees and immigrants: giardiasis (Giardia lamblia).

PMID- 11836829
TI  - Worth their weight in gold: the role of clinical coordinator in a family nurse
      practitioner program.
AB  - PURPOSE: To identify key functions and responsibilities of the role of clinical
      coordinator in a family nurse practitioner (FNP) program. DATA SOURCES: Recent
      articles, research, and interviews with other faculty serving as clinical
      coordinators in FNP programs at five other universities. CONCLUSIONS: Clinical
      coordinators are extremely valuable members of the NP education team; they are
      worth their weight in gold. They support NP programs by assisting in the
      coordination of student-oriented placement and needs-based clinical activities,
      in the recruitment and retention of preceptors and clinical agencies, and in
      providing updated information related to various student resources. IMPLICATIONS
      FOR PRACTICE: It is important that this complex and valuable role be better
      understood and appreciated by university administrators and other faculty.
      Clinical coordination in a distance learning program can take up to three fourths
      release time for a faculty. The role of the clinical coordinator is diverse, not
      easily learned, and requires proficiency in academic advising, administration,
      and clinical supervision.

PMID- 11836830
TI  - Allergic rhinitis: a growing primary care challenge.
AB  - PURPOSE: To describe the growing problem of allergic rhinitis (AR) and the latest
      recommendations on its diagnosis and management for the nurse practitioner (NP)
      in primary care settings. DATA SOURCES: Recent clinical research, review articles
      and consensus guidelines, and the author's clinical experience. CONCLUSIONS: The
      prevalence of AR is increasing, possibly due to increased airborne pollutants,
      poor ventilation, and rising levels of indoor allergens. Allergic disease is
      systemic and rarely involves a single symptom. Treatments include reducing
      exposure to allergens as well as pharmacotherapy. IMPLICATIONS FOR PRACTICE:
      Patient education is crucial for successful management and includes understanding
      the allergic basis of symptoms, reducing allergen exposure, understanding proper
      use of medications, and reassessing the plan on a regular basis.

PMID- 11836831
TI  - Management of a patient with post-polio syndrome.
AB  - PURPOSE: To describe the current understanding of the management of patients with
      post-polio syndrome (PPS) and relate the research to a case study. DATA SOURCES:
      Standard neurology textbooks, current review and research articles, and a case
      study. CONCLUSIONS: More than 15 years following a diagnosis of poliomyelitis, a
      new onset of weakness, fatigue, joint pain, decreased endurance, muscle atrophy,
      gait disturbance, respiratory and swallowing problems, cold intolerance, and
      difficulties with activities of daily living might indicate a neurologic disorder
      called PPS. IMPLICATIONS FOR PRACTICE: Non-post-polio causes of weakness, fatigue
      or pain must be excluded before making a diagnosis of PPS. Approaches to
      management vary depending on the symptoms and level of disability. Reducing
      physical and emotional stress, energy conservation, adequate rest, modification
      of work and home environments, joint protection, and the use of orthoses,
      adaptive equipment, or mobility aids can reduce fatigue and preserve function.

PMID- 11836823
TI  - [General medical information. History of dental radiography].

PMID- 11836832
TI  - House calls: is there an APN in the house?
AB  - PURPOSE: To report how a group of geriatric advanced practice nurses (APNs)
      participated in a house calls program that increased access to care for homebound
      and frail community-dwelling elders. DATA SOURCES: Selected literature and author
      experiences, illustrated with clinical examples. CONCLUSIONS: Many frail older
      adults are unable to access healthcare due to functional impairments related to
      multiple, chronic medical conditions. Many of these adults inappropriately
      utilize the emergency department for episodic care. IMPLICATIONS FOR PRACTICE:
      The model of care maximizes utilization of APNs to provide cost effective,
      culturally sensitive, quality care. The goal of geriatric assessment and primary
      care in this practice is to add quality to later years of life, promoting dignity
      and comfort to older adults and their families.

PMID- 11836833
TI  - Primary healthcare provider's lost opportunity to help abused women.
AB  - PURPOSE: To determine how often primary care providers have the opportunity to
      assess and intervene for intimate partner violence (IPV) in a population of women
      who are known to be experiencing IPV. DATA SOURCES: A convenience sample of 149
      abused women presenting to the justice system for protection orders or to file
      assault charges against in intimate partner were interviewed about the date and
      reason for her last healthcare visit, whether she had been screened for IPV, and
      the presence of selected conditions, medication use, and hospitalizations.
      CONCLUSIONS: Although 86% (n = 128) of the women had sought healthcare services
      within the previous year, only 24% (n = 36) had been assessed for IPV.
      IMPLICATIONS FOR PRACTICE: Abused women use healthcare services at higher rates
      and have more health conditions than non-abused women. Despite recommendations of
      professional organizations, health providers have low rates of screening for IPV.
      Universal screening for IPV by nurse practitioners could substantially interrupt
      ongoing abuse.

PMID- 11836835
TI  - Management of toxic epidermal necrolysis.
AB  - Toxic epidermal necrolysis, a rare and often fatal disease, mimics second degree
      burns and requires the expertise of an interdisciplinary team approach as used in
      burn centers. This article explores the diagnosis and acute and long-term
      treatment approaches. Readers will learn how effective treatment can improve
      outcomes and maximize recovery from this devastating disease.

PMID- 11836834
TI  - Utilization of an elastomeric continuous infusion device to maintain catheter
      patency.
AB  - The frequency of vascular access device (VAD) complications increases with the
      complexity of therapy or poor catheter maintenance. Catheter occlusions are most
      frequently caused by inadequate catheter flushing or technique. The study group
      of 25 patients was placed on an elastomeric continuous infusion device with
      patient costs and occlusion rates compared with historic data. The use of the
      elastomeric continuous infusion device saved an average of $123 per week when
      compared with traditional flushing devices, which cost from $216 to $248 per
      week. The incidence of catheter patency loss was reduced by 50%. The nurses also
      reported considerable timesaving in catheter maintenance and patient education
      and an overwhelmingly positive response from staff and patients.

PMID- 11836836
TI  - The infusion nurse and patient complication rates of peripheral-short catheters.
      A prospective evaluation.
AB  - The objective of this study was to compare catheter-related complication rates in
      patients who had infusion devices placed by infusion nurses with complication
      rates in patients who had devices placed by generalist nurses. The data
      demonstrated that peripheral infusion devices placed by infusion nurses exhibited
      a statistically significant lower rate of leakage, phlebitis, and infiltration
      complications and remained in the vein significantly longer than those placed by
      generalist nurses. However, significance was not achieved with pain complication
      rates between the two groups. The implications of these outcomes for staff
      development and quality of patient care are discussed.

PMID- 11836837
TI  - Nutrient recommendations for wound healing.
AB  - Current knowledge about nutritional therapy and wound healing in humans is
      presented in this review. Recommendations for vitamins A, C, and E, zinc,
      protein, arginine, and water, as well as their roles in wound healing, are
      discussed. Where available, scientific data supporting each recommendation are
      included, along with assessment methods. A brief overview of the wound healing
      process is presented.

PMID- 11836838
TI  - Pain as the fifth vital sign.
AB  - Patients who do not report pain and healthcare providers who fail to assess for
      pain are major barriers to the relief of pain. Using pain as the fifth vital sign
      and being knowledgeable about pain assessment and management can help nurses and
      other healthcare providers overcome many of the barriers to successful pain
      control. A successful pain control plan includes establishing the pain diagnosis,
      treating the cause of the pain when possible, optimizing analgesic use,
      implementing nonpharmacological interventions to maximize physical and
      psychological comfort and function, and referring the patient for invasive pain
      management options when indicated.

PMID- 11836839
TI  - New treatment modalities in radiation therapy.
AB  - Radiation therapy is used for cure, control, and palliation of cancers in more
      than 60% of cancer patients. It is used alone as well as in combination with
      surgery and chemotherapy. The goal of radiotherapy is to treat the cancer and
      spare the normal tissue as much as possible. Advances have been made that allow
      delivery of higher doses of radiation to the tumor while sparing a greater amount
      of surrounding tissue, thus achieving more cures and fewer acute and long-term
      side effects. This article describes several of the new treatments along with the
      effects of radiation on the cells and tissues. Technological advances and
      research will continue to result in improvements in the field.

PMID- 11836840
TI  - Peripheral intravenous therapy-related phlebitis rates in an adult population.
AB  - To determine the incidence of peripheral intravenous therapy-related phlebitis in
      an adult population, 305 peripheral i.v. catheter sites were observed from the
      time of admission of the patient (or initiation of the first peripheral i.v.
      catheter) to the time of the participant's discharge from the facility (or 48
      hours after the removal of the final catheter). Parameters monitored included
      patient demographics, diagnosis, i.v. fluids and medications, type of peripheral
      catheter, dwell time, and dressing integrity. Results showed that of the 10 cases
      of phlebitis found in nine study subjects, all were associated with catheters
      indwelling less than 72 hours. In three cases, although the catheter site was
      clear at the time of catheter removal, postinfusion phlebitis developed within 24
      hours. Catheter site locations, diagnoses, medications, and i.v. fluids in these
      cases were varied.

PMID- 11836841
TI  - Designing a health outcomes research study in infusion nursing practice. How to
      get from a great idea to research results.
AB  - In infusion nursing practice, outcomes research involves identifying and
      measuring outcomes sensitive to, and most consistent with, current infusion
      nursing practice and theory. This article discusses what outcomes should be
      measured in infusion nursing; how to frame the study problem, develop a working
      research question, and define study variables; and how to design the method for
      sampling, variable measurement, data collection, and proposed data analysis. The
      article concludes with a discussion of how to apply research components using
      retrospective descriptive-comparative and prospective experimental approaches,
      and details how to write up the final research report.

PMID- 11836842
TI  - Intravenous support for the patient in sickle cell crisis.
AB  - Sickle cell episodes (otherwise known as crises) are inevitable complications of
      sickle cell disease (SCD). Successful management of these episodes includes
      hydration, medication administration, and blood transfusion. Intravenous support
      is an essential component in the management of sickle cell-related complications.
      This article gives an overview of SCD and its complications and treatments,
      focusing on infusion therapy support of the patient during a sickle cell episode.

PMID- 11836844
TI  - Innovative antineoplastic agents.
AB  - Cancer treatment options are changing as a result of extensive research efforts.
      New drugs and drug combinations proceed through specific phases of clinical
      research leading to possible Food and Drug Administration review and approval.
      Phase I, II, III, and IV clinical trials have detailed enrollment criteria and
      treatment plans designed to determine research objectives. These objectives can
      include reduction of toxicity, increased efficacy, and improved quality of life.
      Liposomal drug formulations, monoclonal antibody therapies, and cytoprotective
      agents are some of the new treatment approaches that have shown promise in
      clinical trials. This article reviews the clinical trial process, several
      innovative therapies, and the nursing responsibilities associated with caring for
      the patient with cancer.

PMID- 11836843
TI  - Central venous catheters for infusion therapy in gastrointestinal cancer. A
      comparative study of tunnelled centrally placed catheters and peripherally
      inserted central catheters.
AB  - Protracted venous infusion of 5-fluorouracil (5-FU) is a common treatment for
      patients with gastrointestinal malignancy. A central venous access device is
      required for safe and effective drug delivery. This study uses a survival
      analysis to compare the useful life and treatment completion success of tunelled
      centrally placed catheters (TCPCs) and peripherally inserted central catheters
      (PICCs). It also describes complications found with both devices. Data on
      insertion, complications, and removal of TCPCs and PICCs were collected on
      standardized forms, prospectively for initial PICCs and retrospectively for
      initial TCPCs. Survival of indwelling catheters was similar for both devices for
      the first 120 days, but after that TCPC survival was statistically better than
      that of PICCs (P = 0.051). Complications occurred in 61% of patients with TCPCs
      and 67% of patients with PICCs. The authors conclude that PICCs provide less
      invasive, more cost-effective, and easier to schedule central venous access for 5
      FU infusion; however, their advantage over TCPCs decreases significantly in
      treatments lasting more than 120 days.

PMID- 11836846
TI  - New therapeutic approaches for the treatment of Huntington's disease.
AB  - The use of transplantation (TR) of fetal neural tissue as a therapeutic method
      started much later in patients suffering from Huntington's disease (HD) than in
      those with Parkinson's disease. The clinical trial, following a wide range of
      animal experiments (neurotoxic models and newly also transgenic mice), includes
      about 30 HD patients until now. Because of limited use of the human fetal tissue
      by ethical and technical concerns, there is necessity to search for the
      alternative sources for neural grafting. The first attempt with
      xenotransplantation (in 12 HD patients) and with TR of encapsulated genetically
      modified cells (in 6 HD patients) was performed, but no appreciable improvement
      of status in any of those patients was noted. Since no effective pharmacological
      treatment of HD is available, the TR of fetal neural tissue is now the only
      therapeutic approach which provides a reduction of symptoms in most of grafted
      patients. The possibilities are enormous offered by neural stem cells, optionally
      by embryonic stem cells, which could be expanded in cultures, cloned or
      genetically modified and then grafted into the patient's brain. On the other
      hand, the neural progenitor and stem cells, normally present within the
      subependymal layer of the lateral brain ventricles also in adulthood, might be
      induced to become an endogenous source of glia and neurons participating in the
      brain's repair.

PMID- 11836845
TI  - Where is the theory to support infusion nursing?
AB  - Even though there has been a dramatic increase in both the type and number of
      nursing theories, the infusion nursing specialty remains without a theoretical
      base. This article addresses the need for and types of infusion nursing theory.
      The obstacles to theory development, including the theory-practice gap in
      nursing, are examined in terms of their relevance to the infusion specialty.
      Suggestions for beginning to create a professional environment conducive to
      generating infusion theory and simultaneously bridging the theory-practice gap
      are introduced.

PMID- 11836847
TI  - Apoptosis and bcl-2 expression in irradiated lungs and the effect of
      pentoxifylline.
AB  - We measured number of bcl-2, apoptotic, neutrophil, and surfactant apoprotein D
      (SP-D) positive cells in irradiated rat lungs during different time points after
      the sublethal whole-thorax irradiation of rats. We also investigated the
      influence of pentoxifylline (PTX) therapy on these markers. Wistar rats were
      given 15 Gy thoracic irradiation and PTX (35 mg/kg) twice a week. Animals were
      examined histologically and imunohistochemically at intervals from 1-12 weeks. In
      non-treated rats compared with treated rats, bcl-2 expression was significantly
      inhibited from 4 weeks after irradiation. A higher apoptosis presence in non
      treated rats from 4 weeks was found and apoptosis development in PTX-treated
      animals was delayed and started 8 weeks after irradiation. Similar differences
      were measured during neutrophil granulocytes examination. Neutrophil penetration
      in non-treated rats was found 5 weeks after irradiation in contrast to the RP
      onset of PTX-treated animals 8 weeks after irradiation. The number of SP-D
      positive cells in non-treated rats observed until 5 weeks after irradiation was
      higher than in the control group. PTX-treated animals expressed higher number of
      SP-D positive cells during the whole experiment than the control group. We
      suggest that apoptosis is linked to neutrophil granulocyte actions during the RP
      onset and that PTX-therapy causes diminished inflammation development.

PMID- 11836848
TI  - Electrophysiological testing of dyslexia.
AB  - We enlarged our previous study (Kubova Z. et al. Physiol Res 1995;44:87-89)
      giving an evidence about magnocellular pathway involvement (delayed motion-onset
      visual evoked potentials (M-VEPs)) in 70% of dyslexic children. In the new group
      presented here, only 48% of 25 dyslexics displayed prolonged latencies of
      cortical responses to motion stimuli. However, there was no correlation of this
      defect with the used quantification of the reading skills (reading quotients). No
      significant EEG frequency spectrum changes were found. 10 subjects from the
      former group, who were re-examined 4 years after the previous study at the mean
      age of 14 years, exhibited significant shortening of the M-VEP latencies compared
      to the original values. Also in control subjects a distinct improvement in
      magnocellular pathway function was proved (in M-VEP re-examination after 4
      years). These results document rather late maturation of the magnocellular
      pathway, which is evident mainly in dyslexic children. In both groups of
      dyslexics an effect of colour in moving stimuli was also tested to verify the
      reported effect of light wavelengths onto the magnocellular pathway function.
      However, no latency differences among grey, green, pink, yellow and blue stimuli
      were observed.

PMID- 11836850
TI  - Lumbar and femoral bone mineral density in type 2 Turkish diabetic patients.
AB  - The relationship between type 2 diabetes and osteoporosis has not been well
      established. We studied a population composed of 161 post-menopausal women with
      type 2 diabetes and a control group. We examined bone mineral density with the
      dual-energy X-ray absorptiometry(DXA) technique at the lumbar and femoral regions
      and in a subgroup of patients, we also measured the levels of markers of bone
      remodelling. We found significantly higher levels of bone mineral density at the
      lumbar and femoral levels in the diabetic subjects compared with the control
      group. Moreover, we found higher level of urinary calcium in the controls. On the
      basis of these results, we suggest that osteoporosis cannot be considered a
      complication of type 2 diabetes.

PMID- 11836849
TI  - The effect of trimetazidine on C-reactive protein, cytokines and adhesion
      molecules in the course of acute myocardial infarction.
AB  - The aim of this randomised, double-blind, placebo controlled, parallel group
      study was to assess the effect of trimetazidine (TMZ), a potent antiischaemic
      drug, on plasma C-reactive protein (C-RP), cytokine and adhesion molecule levels.
      The study population consists of 18 patients (16 males, 2 females, average age
      56.45 +/- 10.97 years) with acute myocardial infarction admitted within 6 hours
      after onset of symptoms and treated with streptokinase. Blood samples were taken
      at 3-hour intervals during the time of treatment. All patients were randomised
      blindly using a centralised randomisation process, between trimetazidine (40 mg
      bolus i.v. then 60 mg per day for 48 hours intravenously in glucose infusion) or
      placebo group. Plasma C-RP level was significantly lower in TMZ group (39.5 mg/ml
      +/- 9.7 mg/ml) as compared to placebo (75.7 +/- 29.4 mg/ml, p < or = 0.001) and
      peaked 28 hours later in TMZ group. Plasma interleukin 6 (IL 6) level showed a
      sharp peak 9 hours after the onset of the symptoms in TMZ group (116.9 +/- 180.2
      pg/ml vs. 45.4 +/- 37.9 pg/ml) and was increased up to 30 hours after the onset
      of the symptoms. Plasma interleukin 1 beta (IL 1 beta) was also higher in TMZ
      group notably 21 hours after the onset of symptoms (26.4 +/- 9.3 pg/ml vs. 16.2
      +/- 2.4 pg/ml). TMZ group showed lower plasma E-selectin levels. Plasma IL 8, TNF
      alpha and ICAM 1 levels were without statistical significant differences. The
      present study demonstrates a significant reduction of plasma C-reactive protein
      level in the course of acute myocardial infarction treated with streptokinase and
      intravenous trimetazidine infusion compared with the group of patients without
      trimetazidine treatment.

PMID- 11836851
TI  - Increasing quality of anatomical education by introduction of digital imaging
      into documentation of topographic dissections.
AB  - Knowledge of topographic anatomy is essential prerequisite for any physician to
      be successful in professional career. That is why we pay special attention to
      topographic dissections completing course of normal human anatomy at our
      department. Dissection procedure is subjected to relatively rigid rules demanding
      removal of some superficial structures during preparation of deeper layers. Thus
      some important structures get lost for further learning and also for final
      evaluation of students knowledge and manual skills. Therefore we decided to
      introduce digital imaging into the recording of course of preparation, the
      topographic relationships and unique variations. Digital acquisition of pictures
      through still digital camera makes possible to bypass the wet photographic
      process and provides instant graphic inputs for further computer processing. The
      image files can be further edited, printed, archived on various media and then
      may be used for instructional, test, evaluative, and publication purposes.
      Moreover, own original pictorial material is feasible to be presented at anatomy
      lectures. Practical results of this new approach, besides higher attractiveness
      and motivation impact, allow us to conclude that systematic digital acquisition
      of dissection pictures combined with computer processing fairly increases quality
      of anatomical education.

PMID- 11836853
TI  - Group visits encouraged for chronically ill adults.

PMID- 11836852
TI  - Inflammatory response to acute myocardial infarction complicated by cardiogenic
      shock.
AB  - We report a case of a 60-year-old man with acute myocardial infarction (AMI)
      treated using thrombolysis, and complicated by cardiogenic shock (CS). Plasma
      interleukin (IL) 1 beta, IL 6, IL 8, tumor necrosis factor alpha (TNF alpha), and
      soluble adhesion molecule (sICAM 1, sE-selectin) levels were measured at 3-h
      intervals. This observation showed the effect of AMI and CS on the plasma
      interleukin levels. Remarkable changes were found in the plasma TNF alpha level,
      which reached two significant peaks. The peak of the first elevation caused by
      AMI (80.11 pg/ml, vs. normal value 4.35 pg/ml, SD 21.3 pg/ml) was seen 6 h after
      the onset of the symptoms. After the period of significant decrease, TNF alpha
      level was increasing until the end of the observation period because of CS (the
      last TNF alpha level was 204.1 pg/ml). The plasma IL 1 beta level was continually
      increased during the period of observation (maximal IL 1 beta level 32.1 pg/ml,
      normal value < 10 pg/ml). The plasma IL 6 level reached the first peak caused by
      AMI nine hours after the onset of the symptoms (362.85 pg/ml, normal value (10
      pg/ml). Because of CS, after the short period of decrease, the plasma IL 6 level
      was increasing until the end of the observation period (the last IL 6 level was
      859.61 pg/ml). The plasma IL 8 level was also elevated throughout the time of
      observation (max. value 1652 pg/ml, vs. normal value < 30 pg/ml). The soluble
      adhesion molecule levels (sE-selectin and sICAM 1) were elevated throughout the
      period of observation without any significant peak.

PMID- 11836855
TI  - Guidelines set new benchmark for emergency care of children.
AB  - This spring, the American College of Emergency Physicians and the American
      Academy of Pediatrics issued joint guidelines on providing optimal care to
      children who visit emergency departments--more than 20 million visits annually.
      The guidelines raise the bar on pediatric emergency care and offer new benchmarks
      for EDs.

PMID- 11836854
TI  - Mentor-driven cardiovascular risk-reduction program makes a strong case for
      prevention.
AB  - CVD is the biggest killer of Americans, but many experts agree that traditional
      medicine is too focused on fixing cardiac problems rather than preventing them.
      Further, there is evidence that even modest efforts which focus on behavior
      change can make a significant dent in utilization. See how one mentor-based
      program is helping providers give their patients the preventive guidance and
      support they need.

PMID- 11836856
TI  - Asthma emerges as significant problem for elderly.

PMID- 11836857
TI  - Researchers test system to custom-tailor guidelines.
AB  - Do you ever want to adapt standard guidelines to fit the demographic and clinical
      characteristics of particular patient population? It'll be possible sooner than
      you think.

PMID- 11836858
TI  - Creativity: the other side of management.

PMID- 11836859
TI  - Congress fails to address 2002 Medicare fee reduction.

PMID- 11836860
TI  - Is there a pay raise in your future?

PMID- 11836861
TI  - Digital doctoring today.... ...DNA doctoring and nano-doctoring tomorrow.

PMID- 11836862
TI  - A little CAREing goes a long way. Responsiveness to patients essential to
      practice success.

PMID- 11836863
TI  - Sometimes you have to terminate to renegotiate.  Keep track of key contract
      dedlines.

PMID- 11836864
TI  - Initiative + innovation + technology. Combination leads to streamlined phone
      service in ENT practice.

PMID- 11836865
TI  - Seizing the technology advantage. Everett Clinic's investment pays off.

PMID- 11836866
TI  - Train 'em and reap. A structured training program for front- and back-office
      staff.

PMID- 11836868
TI  - Don't get out of joint. Physicians and hospitals should pursue joint ventures
      prudently.

PMID- 11836869
TI  - ASP 101. Outsource information management with an application service provider.

PMID- 11836867
TI  - On board. How a physician becomes an effective member of your medical group's
      board of directors.

PMID- 11836870
TI  - Stage your medical practice as a strategic entity. Lessons learned from a growing
      multispecialty practice.

PMID- 11836871
TI  - Survival in the practice management business. For success match your style with
      the organization's.

PMID- 11836872
TI  - Defer to refer? Giving references and avoiding legal liability.

PMID- 11836873
TI  - Get your practice on the Web. Are you ready for knocking on your 'virtual door'.

PMID- 11836875
TI  - [The collagen of the restenosis post angioplasty with stent: Is its origin in
      intima or adventitia?].
AB  - BACKGROUND: Restenosis post stenting is due to the deposit of extracellular
      matrix, mainly collagen in the neointima. Controversy exists regarding if
      collagen is generated locally or by immigration from the adventitia. AIM: To
      study the fibrocellular response after stent implantation in rabbit iliac
      arteries. To observe, by immunohistochemistry and in situ hybridization, if
      collagen type I mRNA is expressed in the neointima, in the media or in the
      adventitia. MATERIAL AND METHODS: Thirty eight white rabbits (New Zealand) of 4
      kg received an hypercholesterolemic diet during 1 month. After this period, in
      all but 6 of them, an angioplasty with stent implantation was performed via right
      carotid artery in both iliac arteries, using a 1:1.3 relationship regarding the
      reference vessel. Angiograms were performed at day 0, 4, 21, and 40, followed by
      paraffin fixation of the injured segments, immunohistochemistry for alpha-actin
      and in situ hybridization to detect procollagen type I (alpha 1R1) mRNA. RESULTS:
      No hybridization was observed in non injured arteries or at day 0 (n = 6).
      Expression of alpha 1R1 mRNA was observed in the neointima starting at day 4
      after stenting (n = 8). At day 21 (n = 8) hybridization of procollagen type I was
      not only observed in the neointima, but also in the media, which became equally
      intense in both areas. At day 40 (n = 6) hybridization was observed similarly in
      the media and adventitia. CONCLUSIONS: In this model, hybridization of
      procollagen type I started in the neointima, then involved the media and finally
      the adventitia. This finding might be useful for designing therapies to be
      delivered locally at the end of an angioplasty to prevent collagen deposition in
      the neointima.

PMID- 11836876
TI  - [Serum levels of soluble CD30 molecule in hepatitis B virus infection].
AB  - BACKGROUND: The release of CD30 molecule in the soluble form (sCD30) is
      considered a feature of Th2 activation and proliferation of the cellular
      phenotype Th2. AIM: To analyze the immunoregulatory role of sCD30 in the
      evolution of hepatitis B virus (HBV) infection. PATIENTS AND METHODS: Three study
      groups were formed: 15 patients with acute infection by HBV who remitted toward
      the resolution of the infection; 15 patients who evolved to the carrier state and
      15 subjects without clinical history of infection by this or other viruses. The
      determination of serological markers for the HBV was done by the Microparticles
      Enzymatic Immunoanalysis techniques (MEIA). The method of double antibody by
      ELISA was used For sCD30 determination. RESULTS: A significant sCD30 increase (p
      < 0.05) was observed in patients with acute infection, during the acute phase
      (135.7 +/- 36.7). These values decreased to 16.2 +/- 2.5 during the convalescent
      phase. Patients that evolved to the carrier state, did not experience a rise in
      sCD30 values (40.2 +/- 6.7, 38 +/- 9.2 and 36.1 +/- 8.3 during the acute phase,
      at 120 and 240 days respectively). The value in the control group was 34.8 +/-
      6.7. CONCLUSIONS: The group that evolved towards remission experienced a higher
      activation of the Th2 cellular phenotype, promoting humoral immune response. An
      inactivity of sCD30 values was observed in the group that evolved to the carrier
      state.

PMID- 11836877
TI  - [Risk factors for morbidity and mortality in patients with essential
      hypertension, followed for 25 years].
AB  - BACKGROUND: Among hypertensive patients, other risk factors for mortality and
      morbidity, besides blood pressure, must be considered when therapeutic decisions
      are done. AIM: To assess the incidence and relevance of cardiovascular risk
      factors in a cohort of patients with essential hypertension. MATERIAL AND
      METHODS: A cohort of 1,072 treated patients with essential hypertension was
      followed for a period up to 25 years. Four hundred eighty six were men and 586
      were women, age ranged from 31 to 70 years. At entry, 56% of subjects did not
      have any organic complications associated to hypertension (stage I WHO criteria),
      30% had mild alterations (Stage II) and 14% had major complications (myocardial
      infarction, stroke, heart failure or renal failure). Likewise, 43.8% had mild,
      14.5%, moderate and 41.7%, severe hypertension. Patients were treated with
      monotherapy or combined therapy based on diuretics, beta blockers, calcium
      antagonists and angiotensin converting enzyme inhibitors. Goal of therapy was
      140/90 mm Hg. Risk factors associated diseases and complications were registered
      carefully. Causes of death were obtained from hospital records and death
      certificates. Mortality was analyzed using life tables (intention to treat method
      included). RESULTS: Blood pressure dropped significantly during follow up from a
      mean of 182/110 to 154/92 mm Hg. During follow up, 143 patients died and 429
      complications (lethal or non lethal) were recorded. Twenty four percent of
      patients smoked, 24% reported alcohol intake, 56% had hypercholesterolemia, 11%
      were obese, 13% had diabetes and 3% had gout. The proportional hazard model
      showed that the existence of previous complications, the presence of more than 3
      risk factors, and age over 60 and mean systolic and diastolic pressure during
      therapy, were independent and significant risk factors for mortality.
      CONCLUSIONS: The incidence of risk factors among our hypertensive patients is
      very similar to that of other national or international cohorts.

PMID- 11836874
TI  - [Safety profile of statins].
AB  - HMG-CoA reductase inhibitors (statins) are the treatment of choice for patients
      with hypercholesterolaemia. Several large-scale clinical trials have examined the
      efficacy and tolerability of statins, providing a wealth of information on their
      safety and adverse effect profile. Adverse hepatic effect is reflected as
      asymptomatic elevations in serum levels of aminotransaminases. Myopathy,
      occasionally leading to myoglobulinuria secondary to rhabdomyolysis, is a rare
      and potentially fatal complication. Cerivastatin, the last statin approved for
      use in humans, was voluntarily withdrawn from the market by Bayer, because fatal
      rhabdomyolysis was most frequently reported with cerivastatin than for other
      approved statins. The concomitant use of statins with drugs that inhibit CYP3A4
      (cyclosporin, erythromycin, clarithromycin, itraconazole, and ketoconazole), may
      result in increased plasma concentrations of HMG-CoA reductase inhibitors leading
      occasionally to myotoxicity. Fibric acid derivatives can produce myotoxicity, and
      the association of both types of drugs increases the risk of this adverse event.
      The reason for the greater association of rhabdomyolysis with cerivastatin than
      with other statins is unknown. The efficiency of post marketing drug surveillance
      programs in different countries, was the clue for the awareness of this problem.

PMID- 11836878
TI  - [Estimation of low density lipoprotein cholesterol concentration: regression
      analysis versus Friedewald's formula].
AB  - BACKGROUND: The Friedewald formula is used to estimate cholesterol of low density
      lipoprotein (LDL) from total cholesterol (CT), cholesterol of high density
      lipoprotein (HDL) and triglycerides (TG), but there are doubts about its
      precision. AIM: To compare Friedewald formula and regression analysis for the
      calculation of LDL cholesterol. MATERIAL AND METHODS: One hundred and fifty
      plasma samples from asymptomatic adults (aged 47.7 +/- 13 years, 50.6% male) were
      analyzed. CT, HDL, LDL and TG were determined by enzymatic methods. Friedewald
      formula (LDLc = CT-HDL-(TG/5)) and multiple regression analysis were applied to
      estimate LDL concentration. RESULTS: Mean total cholesterol was 175.3 +/- 39.7
      mg/dl, HDL cholesterol was 35.57 +/- 0.8 mg/dl and TG was 128.4 +/- 65.4 mg/dl.
      Mean values for LDL cholesterol were significantly higher than those estimated by
      the Friedewald formula (136.4 +/- 37.9 mg/dl and 114.1 +/- 37.4 mg/dl
      respectively, p < 0.001) with a mean underestimation of 16.4 +/- 11.7%. LDL
      cholesterol values were directly proportional to TG concentration. Multiple
      regression analysis (LDLr = -14.376 + (age x 0.198) + (CT x 0.949) + (HDL x 
      0.474) + (TG x -0.064) showed no statistical differences with those obtained by
      the enzymatic method. CONCLUSIONS: These results confirm the underestimation of
      LDL concentration by the Friedewald formula despite normal range of TG
      concentration. A multiple regression analysis should be used to estimate LDL
      concentration with precision.

PMID- 11836880
TI  - [Prevalence of psychiatric disorders in men and women hospitalized in a internal
      medicine service of a hospital of Santiago, Chile].
AB  - BACKGROUND: Mental disorders may interfere, aggravate or mimic medical
      conditions. AIM: To study the prevalence of psychiatric disorders among patients
      hospitalized in a medical ward of a general hospital. PATIENTS AND METHODS: A
      structured interview for DSM-III, devised for "non patients", was applied to 203
      men and 203 women, aged 11 to 90 years old, hospitalized in an internal medicine
      service of a public hospital. Thirty four psychiatric conditions that can be
      discriminated with the instrument and others that complied with DSM-III criteria,
      were investigated. RESULTS: There was a 60% prevalence of mental disorders among
      men (alcohol dependency in 26%, delirium or dementia in 10.8%, anxiety disorders
      in 10.4%, major depression in 7.8% and adaptation disorders in 3%). Among women,
      the prevalence of mental disorders was 65% (major depression in 23.2%, anxiety
      disorders in 14.3%, adaptation disorders in 8.4%, dementia in 5.6%, delirium in
      3% and alcohol dependency in 2.5%). Most conditions were of moderate or mild
      intensity. Two or more conditions coexisted in 40% of cases. Only in 8% of these
      subjects, a psychiatric consultation was requested. CONCLUSIONS: There is a high
      frequency of psychiatric disorders among medical patients. These must be
      adequately diagnosed and treated.

PMID- 11836881
TI  - [Pleural effusion and complicated empyema in children. Evolution and prognostic
      factors].
AB  - BACKGROUND: Complicated pleural empyema has a torpid and longer clinical
      evolution, requiring in some patients surgical management. The predictive factors
      for surgical treatment are not well known. AIM: To search for clinical,
      laboratory or radiological predictors for the requirement of surgical treatment
      in pediatric patients with empyema. PATIENTS AND METHODS: A retrospective review
      of the charts of 108 patients hospitalized for pneumonia plus pleural effusion at
      the Pediatric Service of the Catholic University Hospital between January 1985
      and July 2000. RESULTS: Eighty one patients had complete radiological evaluation
      and pleural fluid biochemical analysis. Forty nine (60%) fulfilled the criteria
      for empyema and 32 (40%) for an exudate. Thirteen patients with empyema required
      surgery and 36 were treated medically. The mean age was 3 years (range 9 months-6
      years) for the surgically treated and 4 years (range 12 months-14 years) for the
      non-surgical group. The male/female ratio was 5:1 in the surgical group and 1:1
      for the non-surgical group. Pleural fluid cultures were positive in 21 of 79
      patients. Streptococcus pneumonia was the most frequently isolated agent. No
      significant differences were found between groups for the average days of fever
      prior to the diagnosis or total days of fever, days of hospital stay, pleural
      fluid pH (6.8 and 7.0 respectively) and glucose (21 and 31 mg/dl respectively).
      No differences were either observed for pleural fluid risk factors (pH < 7 and
      glucose < 20 mgdl), the presence of extensive pleural effusions, pleural
      loculations or bands on pleural ultrasonography and positive Gram stain or
      cultures in the pleural fluid. Surgical patients required oxygen for more days
      than medical patients (7.7 and 5.1 days; p = 0.037). CONCLUSIONS: This study
      failed to find predictive clinical, radiological or pleural fluid parameters, for
      the requirement of surgical treatment of empyema.

PMID- 11836882
TI  - [Causative agents of bloodstream infections in children with neoplasm, in 5
      hospitals of Santiago (1994-1998)].
AB  - BACKGROUND: Pediatric patients in treatment for cancer can have fatal bacterial
      infections. Thus, in the presence of fever or other signs infection,
      antimicrobials have to be prescribed empirically. AIM: To know the causative
      agents of bacteremia in children with cancer, their changes with time and between
      different hospitals and their patterns of susceptibility. MATERIAL AND METHODS:
      We reviewed the blood cultores of children with cancer in five hospitals of
      Santiago, from 1994 at 1998. RESULTS: During the study period, 707 agents were
      isolated. The most frequently isolated species or genus were coagulase negative
      Staphylococcus (43%), Staphylococcus aureus (16%), Escherichia coli (9%),
      Klebsiella spp. (8%), Pseudomonas spp. (5%) and Candida spp. (4%). Coagulase
      negative Staphylococcus was 55% resistant to meticilin and S. aureus was 44%
      resistant. Enterobacteriaceae had 15% resistance to gentamicin and amikacin, 2%
      to imipenem, 26% to ceftriaxone, 21% to cefotaxime and 20% to ceftazidime. Among
      non fermenting agents resistance was 6% for imipenem, 9% for amikacin 10% for
      ciprofloxacin, 19% for ceftazidime and 22% for cefoperazone. The resistance of
      Streptococcus spp. (non pneumoniae) to penicillin reached 50% and that of
      Enterococcus spp. was of 33%. CONCLUSIONS: Treatment for pediatric patients with
      cancer must be modified and new guidelines including more active medications for
      patients at risk for bacteremia, should be devised.

PMID- 11836879
TI  - [Computer analysis of respiratory sounds in bronchial obstruction evaluation in
      small children that do not collaborate with spirometry tests].
AB  - BACKGROUND: There are changes in inspiratory breath sound intensity in patients
      with airway obstruction. Airway narrowing may change sound spectral
      characteristics. AIM: To define the characteristics of lung sounds at
      standardized air flow during methacholine challenge and to compare acoustic
      changes with transcutaneous oxygen tension (PtcO2) during induced airway
      narrowing. PATIENTS AND METHODS: Forty asthmatic children (20 male) aged 5.2 +/-
      1 years and 40 normal children (18 male), aged 5.6 +/- 1 years were studied. All
      patients were free of respiratory tract infections one month before the study. A
      methacholine challenge from 0.06 to 8 mg/ml was performed; the test was ended
      when a fall in PtcO2 of > 20% from baseline was observed or if the final
      concentration was reached. Subjects breathed through a pneumotachograph aiming at
      flows of 0.4 to 0.6 l/s. Respiratory sounds were recorded using contact sensors
      at the suprasternal notch and at the posterior right lower lobe. From average
      spectra, power at low (100-200 Hz = P1) and high frequencies (400-2000 = P2) was
      calculated. Frequencies below which 50% (F50) and 99% (SEF90) of the spectral
      power between 100 and 2000 Hz was contained, were also calculated. RESULTS: In
      asthmatics, the metacholine concentration at which a 20% fall in PtcO2 was
      observed, was lower than in normal children (p < 0.05). There was an increase in
      P1 (p < 0.01) and a reduction in P2 (p < 0.01) during inspiration, in subjects
      that experienced a 20% reduction in PtcO2. Also, there was an increase in F50 and
      SEF99 during inspiration in lung sounds, but not over the trachea. CONCLUSIONS:
      Lung sounds analysis can be useful for the assessment of airway reactivity in
      asthmatic children.

PMID- 11836884
TI  - [Familial and isolated primary hyperparathyroidism. Case report].
AB  - Familial hyperparathyroidism can be a part of a type 1 or 2 multiple endocrine
      neoplasia syndrome, can be associated to mandibular fibromas or can appear as an
      isolated disease. We report a family with 11 members affected by a primary
      hyperparathyroidism, all with a history of kidney stones and without evidences of
      other endocrine tumors. Not knowing the familial history of the disease, only one
      adenoma was resected in four cases and in all, the disease recidivated. Two were
      operated again, performing a total parathyroidectomy and heterologous
      autotransplantation of parathyroid tissue in the forearm. The presentation form
      of primary hyperparathyroidism in this family, is similar to other reported
      cases. It is more aggressive, is diagnosed at a lower age has a higher incidence
      of recurrence and multiglandular involvement than the sporadic disease.

PMID- 11836883
TI  - [Prostate neoplasm prevalence in Talca, VII Region of Chile].
AB  - BACKGROUND: In 1998, there were 1,218 deaths in Chile caused by prostate cancer.
      This figure results in a death rate of 16.6 per 100,000 males for this disease.
      AIM: To assess the prevalence of prostate cancer in the Seventh Region of Chile.
      MATERIAL AND METHODS: A probabilistic sample of 327 males aged 40 to 59 years old
      was studied. In all, a codified questionnaire was applied, a digital rectal
      examination was performed and a blood sample was drawn to measure prostate
      specific antigen. All digital rectal examinations were performed by the same
      observer. Patients with an abnormal rectal examination or prostate specific
      antigen were subjected to a prostatic biopsy under ultrasound guidance. RESULTS:
      In 14 subjects, the digital rectal examination was considered abnormal and in
      seven, prostate specific antigen was over 4 ng/ml. All subjects with elevated
      prostate specific antigen had an abnormal rectal examination. In three of the 14
      subjects, the biopsy showed a well differentiated adenocarcinoma. All three were
      aged over 50 years old. The resulting calculated prevalence of prostate cancer
      was 9.2 per 1,000 males (CI 4.2-14.1). CONCLUSIONS: The cost effectiveness of
      screening for early diagnosis of prostate cancer must be calculated, to decide
      its incorporation in preventive medical examinations.

PMID- 11836885
TI  - [Pulmonary involvement due to disseminated non Hodgkin lymphoma in one patient
      with AIDS].
AB  - Pulmonary involvement due to disseminated non Hodgkin lymphoma (LNH), is an
      unusual cause of lung disease in AIDS patients. We report a 38 years old male
      patient, with advanced AIDS, who, in the course of three weeks, developed cough,
      dyspnea and fever. The chest X ray film showed diffuse thickening of the
      peribronchovascular connective tissue with possible mediastinal lymph node
      enlargement. The evolution was unfavorable with hypoxemia, severe anemia, liver
      damage and elevated levels of lactic dehydrogenase. The presumptive initial
      diagnoses were Pneumocystis carinii pneumonia, pulmonary tuberculosis with
      hematogenous dissemination and Kaposi sarcoma. Definitive diagnosis was made
      through a transbronchial biopsy performed the day before his death. The
      pathological and inmunohistochemical report demonstrated a highly aggressive
      lymphoma (lymphoblastic, B precursor). This finding was confirmed by autopsy that
      revealed multiple organ involvement.

PMID- 11836886
TI  - [Reversible myocardial ischemia in hypothyroidism: Case report].
AB  - A silent, reversible myocardial ischemia with normal coronary angiography and
      reversible with thyroid hormone substitution, has been recently described in
      hypothyroid patients. We report a 49 years old male with an abnormal exercise
      electrocardiogram detected in a preventive medical examination. He had laboratory
      evidence of hypothyroidism and a history of two years of asthenia and progressive
      coarsening of the voice. The Thallium myocardial perfusion study, showed an
      alteration of coronary flow during exercise in the septum and lower wall of the
      left ventricle. Thyroid hormone substitution was started and three months later,
      a coronary angiography was normal. After six months a repeated Thallium perfusion
      study and exercise electrocardiogram were informed as normal.

PMID- 11836887
TI  - [Refractory arterial hypertension and the use of anticonvulsant drugs. Case
      report].
AB  - Resistant arterial hypertension is uncommon when there is good compliance to
      antihypertensive therapy and secondary causes have been ruled out. We report a 41
      years old male that suffered hypertensive encephalopathy and received
      prophylactic anticonvulsant therapy showing progressive raise of arterial
      pressure levels. Renovascular hypertension, aldosteronism and pheochromocytoma
      were discarded and, in spite of combined use of antihypertensive drugs, he did
      not achieve normal blood pressure. When phenytoin was discontinued, blood
      pressure temporarily normalized. Carbamazepine was started and blood pressure
      raised again. It fell when this medication was discontinued. Antiepileptic agents
      could induce drug metabolizing system and thus reduce the effects of
      antihypertensive medications.

PMID- 11836888
TI  - [Medical applications of genome discovery].
AB  - The discovery of the complete base sequence of human genome unveils several
      perspectives to understand human diseases and develop new therapies. Human genome
      contains approximately 39,000 genes of which 26,000 code specific proteins that
      have been identified. There are approximately 1,500 diseases with identified
      molecular disturbances. Genes can modify signs and symptoms of common diseases.
      Thus, there are no pure monogenic diseases. Chronic diseases of adults are
      complex and dependent on multiple factors. Several genes that predispose to
      chronic degenerative diseases have been identified. This is revealing the complex
      nature and the interaction of these ailments with the environment. The discovery
      of bacterial and viral genomic sequences will allow the manufacturing of new
      vaccines and specific molecular antimicrobials. The new pharmacogenomics will
      devise treatments for each subject according to her specific genomic profile. The
      new applications of genomic technology is creating new paradigms in biomedical
      research such as functional genomics, proteonomics, epigenetic regulation. Gene
      diagnosis and therapy will considerably improve the future of medicine.

PMID- 11836890
TI  - [New trends in the regulation of medical practice in the context of health care
      reform: the Mexico case].
AB  - The recent panorama of medical practice regulation in Mexico is exposed. The
      dynamics of regulation changes is observed in different areas, with particular
      intensity in the labor market. Changes seem to be moving towards the constitution
      of a new regulatory model. A full state regulation for the last 50 years, is
      being substituted by a model where private and professional corporations are
      increasing their influence through informal mechanisms of regulation. In the
      constitution of this new model, the presence of a wide variety of actors claiming
      regulatory authority is notorious. Three of these new actors are analyzed: The
      National Commission for Medical Arbitrage, managed care models of medical
      services, and Specialists Certification Councils. The changes that have occurred
      in the process of regulation and its future transformation have an intimate link
      with the reform of the Mexican health care system.

PMID- 11836889
TI  - [The role of connective tissue in the morphology and function of intestinal
      mucosa. Its participation in the pathogenesis of celiac diseases].
AB  - The differentiation, architecture and function of the mucosa of the digestive
      tract is the result of close interactions between the epithelial cells and their
      underlying connective tissue. This interaction not only plays a role in the
      normal morphological organization of the intestinal mucosa but also in the
      organization and maturation of the enterocytes, the development of some of their
      enzymatic activities, the transport of nutrients and the restitution of the
      epithelium following denudation of the surface of villi due to loss of
      enterocytes. It is thought that disturbances of the cells of the connective
      tissue, especially of the myofibroblasts as well as of some of the above
      mentioned mechanisms, participate in the pathogenesis of some gastrointestinal
      diseases, celiac disease among them. This review summarizes some of the knowledge
      in this area.

PMID- 11836892
TI  - Haven't I seen you before?

PMID- 11836891
TI  - [Estrogen replacement therapy in postmenopause: what do we know today].

PMID- 11836893
TI  - Long and the broad of it.

PMID- 11836894
TI  - Social insurance. Not much to write home about?
AB  - Social health insurance systems in Europe are complex and this makes it difficult
      to establish who is paying for healthcare. France and Germany are seeking to
      widen their revenue base through taxation. A wholesale move to SHI in the UK
      would involve significant upheaval and it is not clear what benefits it would
      bring.

PMID- 11836895
TI  - Social insurance. Eastern block.

PMID- 11836896
TI  - First person. The English patient.

PMID- 11836897
TI  - US healthcare. When the law is an asp.

PMID- 11836898
TI  - Power to excel.

PMID- 11836899
TI  - Test value.

PMID- 11836900
TI  - Asbestos alarm.

PMID- 11836901
TI  - Probing medical gas pipeline issues.

PMID- 11836903
TI  - Video communication visions.
AB  - In a recent study, entitled: Study on the Use of Advanced Telecoms by Healthcare
      Establishments, commissioned by the Information Society Directorate General of
      the European Commission, it was emphasised that: "Telecommunications networks and
      services are central to the achievement of seamless care, where patients' needs
      are addressed smoothly and efficiently, by whatever services they need, as and
      when they need it." Video communications, as part of an integrated information
      and communications strategy, has the capability to provide a continuum of care
      throughout a person's lifespan--from the cradle to the grave. Moreover in the
      future, video-enabled healthcare will help the government redesign the health
      service around the patient. It is a fast developing area and estate managers will
      need to be part of any implementation strategy, as exemplified in the IP network
      being developed across the Welsh healthcare estate. Motion Media is a founding
      member of the UK e-Health Association, a circle member of the American
      Telemedicine Association and a member of the European Health Telematics
      Association (EHTEL). The company was chosen recently by the EHTEL to run the
      first approved Telehealth demonstration centre in Europe. In October 2001 Motion
      Media appointed Dr Jay Sanders as its Consulting Medical Director. Dr Sanders is
      known throughout the US healthcare industry as the "Father of Telemedicine."

PMID- 11836904
TI  - Prescription for change.
AB  - From the above it can be seen that, while it is still at an early stage of
      development, the growth of the new profession of facilities management in the NHS
      is already showing that it is highly relevant to the delivery of effective
      healthcare. Hopefully, the points raised in this article will stimulate
      discussion on how estates and facilities services can continue to realign
      themselves to embrace and adapt to changes and challenges. If facilities managers
      are to fulfilL their full potential in the years ahead, it is important that they
      keep their eyes on the shifting horizon with respect to the changes that are
      developing in facilities management. They will need to develop strategies that
      will drive their services forward, while, at the same time, continuing to manage
      the "here and now".

PMID- 11836902
TI  - Construct with constraint and control.

PMID- 11836905
TI  - Technology streamlines maintenance.

PMID- 11836906
TI  - Bedside systems installation needs utmost care.

PMID- 11836907
TI  - ESi does it for King's College.

PMID- 11836908
TI  - Measures to reduce occupational asthma.

PMID- 11836910
TI  - Differential access and utilization of health services by immigrant and native
      born children in working poor families in California.

PMID- 11836909
TI  - Frailty and education in the Hispanic Health and Nutrition Examination Survey.
AB  - This study tests for the presence of education-frailty correlations among 1,176
      Mexican Americans, 522 Cuban Americans, and 560 Puerto Ricans, 50 years and
      older, in the Hispanic Health and Nutrition Examination Survey. Hispanics with
      the least schooling (less than 7 years) were found to have the highest frailty
      rates, and those with the most (more than 12 years of schooling) were found to
      have the lowest frailty rates. Similar, but somewhat weaker, correlations were
      discovered after a measure of self-efficacy was accounted for.

PMID- 11836912
TI  - Cost-effectiveness analysis of a school-based dental sealant program for low
      socioeconomic-status children: a practice-based report.

PMID- 11836913
TI  - Psychiatric symptoms, health services, and HIV risk factors among homeless women.
AB  - The authors determined whether psychiatric symptoms and lack of health and/or
      social services contacts were associated with HIV risk behaviors among a
      probability sample of homeless women. Women were interviewed regarding
      socioeconomic indicators, psychiatric symptoms, health and/or social services
      contacts, and past-year HIV risk behaviors. Overall, 8 percent of the women
      injected drugs, 64 percent engaged in unprotected sex, and 22 percent traded sex.
      Multiple logistic regression results revealed that substance abuse was positively
      associated with injection drug use and trading sex. Homeless women with case
      managers were less likely to inject drugs. Although barriers to obtaining drug
      treatment were associated with trading sex, women attending self-help meetings
      for substance abuse were also more likely to trade sex. Homeless women who are
      substance abusers are vulnerable to HIV risk behaviors. Risk reduction
      interventions for homeless women should be implemented through substance abuse
      and intensive case management programs.

PMID- 11836915
TI  - Income, race, and preventable hospitalizations: a small area analysis in New
      Jersey.
AB  - This research examines the effect of income, race, and cultural factors on
      preventable hospitalizations, using age and sex-adjusted preventable admissions
      from 53 contiguous zip codes in New Jersey from 1993 to 1995. Low income was
      strongly associated with high rates of preventable hospitalization in the study
      zip codes. Income is likely a proxy for education level, barriers to accessing
      primary care, and health insurance. A floor effect of income levels was present
      that may reflect a natural level of preventable hospitalization not affected by
      income, education, or health insurance status. An independent relationship found
      between nonwhite race and high preventable hospitalization may be in part the
      result of delays in seeking care affected by antecedent cultural factors.
      Removing financial barriers is critical but may be insufficient for reducing
      preventable hospitalizations if other barriers are not also addressed.

PMID- 11836914
TI  - Methods of improving funding sources for self-pay patients: a randomized control
      trial of benefits management.

PMID- 11836918
TI  - Determinants of breastfeeding duration in Peninsular Malaysia.
AB  - The health benefits of breastfeeding to infants and mothers have been well
      recognised. This study applies linear regression analysis to assess the
      determinants of breastfeeding duration of first born using data from the Second
      Malaysian Family Life Survey. The proportion of women who breastfed their first
      child is 82 percent, of which 97 percent reported their breastfeeding duration.
      The distribution of breastfeeding duration has a mean of 5.7 months and a median
      of two months. Important determinants of breastfeeding duration include maternal
      age, ethnicity, period of first birth, husband's occupation and work status of
      the woman.

PMID- 11836917
TI  - The temporarily and chronically uninsured: does their use of primary care differ?
AB  - The purpose of this study is to examine differences in the use of preventive or
      early-detection services by the temporarily and chronically uninsured. The use of
      preventive care was measured by an index that depicts the use of nine preventive
      or early-detection services and the use or nonuse of each procedure on the index.
      Respondents whose lapse in insurance coverage was one year or more were
      identified as chronically uninsured, while those whose lapse in coverage was less
      than one year were identified as temporarily uninsured. The analysis indicates
      that the chronically uninsured and, to a lesser extent, the temporarily uninsured
      use significantly fewer preventive or early-detection services than their insured
      counterparts.

PMID- 11836911
TI  - Cervical cancer and black women: an analysis of the disparity in prevalence of
      cervical cancer.

PMID- 11836919
TI  - The quality of life outcome following treatment for lower urinary tract symptoms.
AB  - This study aims to assess the impact of medical and surgical treatment on
      treating lower urinary tract symptoms (LUTS) on pain, prostatic symptoms, disease
      specific quality of life and health-related quality of life. Patients scheduled
      for medical (alpha-blockers) and surgical treatment (transurethral resection of
      the prostate, TURP) were recruited in the study. The patients were assessed using
      the Visual Analogue Scale (VAS), Present Pain Intensity (PPI), International
      Prostate Symptom Score (I-PSS) and Health-Related Quality of Life (HRQOL) at 3
      month, 6-month and 12-month (baseline). Before treatment, most of the patients
      with LUTS had severe pain, LUTS and deterioration of health-related quality of
      life. Following treatment, both medical and surgical treatment improved their
      pain, LUTS and health-related quality of life. Both treatments are effective in
      relieving the symptoms of pain, LUTS and health-related quality of life.

PMID- 11836916
TI  - New Jersey Medical School's unique relationship to its community.
AB  - The Newark, New Jersey, riot of 1967, sparked in part by tensions created by the
      conflicting emphasis of President Lyndon Johnson's Model Cities Program,
      community action programs, and the New Jersey state medical school's move to
      Newark's Central Ward, has profoundly affected the medical school and its
      delivery of medical care in Newark. This paper delineates how these Johnson-era
      programs contributed to the riot and details the continuing legacy of these
      events on the medical school and the delivery of health care in Newark. The paper
      concludes that New Jersey Medical School is expected by its community to have a
      higher standard of local involvement than comparable institutions. Furthermore,
      it suggests that New Jersey Medical School's relationship and commitment to its
      community serve as a model for community interactions for medical schools
      throughout the United States.

PMID- 11836920
TI  - Respiratory symptoms and spirometric observations in relation to atmospheric
      pollutants in a sample of urban population.
AB  - The prevalence of respiratory problems and the ventilatory functions in subjects
      belonging to three sample areas with different levels of pollution was studied to
      ascertain if there is any association between air pollutant levels and abnormal
      ventilatory functions. The predominant activity existing in that area served as
      the basis for stratification of the city into industrial (Group I), commercial
      (Group II) and residential (Group III) areas. Ambient air quality data of
      suspended particulate matter SPM, SO2 and NOx of the three sample areas were
      measured using standard methods. 216 men included in the study were administered
      the American Thoracic Society--Division of Lung Diseases ATS-DLD respiratory
      questionnaire, clinically examined and subjected to routine laboratory
      investigations. Spirometry and salbutamol reversibility tests were performed as
      per the ATS guidelines 1991. The mean and peak levels of SPM in the commercial
      area and the peak levels in the residential area were higher than the National
      Ambient Air Quality Standards (NAAQS). The mean and peak levels of NOx and SO2 in
      all the three areas were lower than the NAAQS. A high prevalence of approximately
      30-50% of respiratory symptoms was reported in the present study. Respiratory and
      ventilatory abnormalities were higher in the commercial areas, which are
      associated with the higher mean and peak levels of SO2 and the peak levels of
      NOx. The pollution control measures should also aim at the peak levels of
      pollutants as they have been shown to exacerbate the respiratory symptoms in the
      present study.

PMID- 11836921
TI  - Blood lead levels of urban and rural Malaysian primary school children.
AB  - The objective of this article is to study the influence of exposure and socio
      economic variables on the blood lead level of Malaysian school children. Data on
      respirable lead and blood lead of 346 school children were obtained from Kuala
      Lumpur (urban), Kemaman (semi-urban) and Setiu (rural). Respirable lead and blood
      lead were highest for Kuala Lumpur (95 ng/m3 and 5.26 micrograms/dL) followed by
      Kemaman (27 ng/m3 and 2.81 micrograms/dL) and Setiu (15 ng/m3 and 2.49
      micrograms/dL), and the differences were statistically significant. The
      percentage of school children with excessive blood lead of 10 micrograms/dL or
      greater was 6.36% overall, and highest for Kuala Lumpur (11.73%). Regression
      analyses show that urban children are at higher risk of exhibiting excessive
      blood lead levels. Kuala Lumpur's school children have a 25 times greater risk of
      having excessive blood lead levels when compared to Kemaman's and Setiu's school
      children. Respirable and blood lead were correlated (r = 0.999, p = 0.021). Urban
      school children acquire higher blood lead levels than their rural and semi-urban
      counterparts, even after controlling for age, sex, parents' education and income
      levels. In conclusion, it is time that lead in the Malaysian environment and
      population be monitored closely, especially its temporal and spatial variability.
      Only then can a comprehensive preventive strategy be implemented.

PMID- 11836923
TI  - Current status of iodine deficiency in Mongolia in 1998-1999.
AB  - In 1992, the Mongolian government conducted a nationwide palpation study of the
      thyroid glands, and the study showed an overall goiter rate of 30%. As a result
      of this, the Mongolian Government launched its Iodine Deficiency Disorders (IDD)
      Elimination Programme in 1996 and its primary strategy was salt iodization. In
      1998 and 1999, we carried out programme monitoring studies in 11 provinces. The
      results showed: among schoolchildren, a goiter rate was 22.8% (n = 6,535), median
      values of urinary iodine excretion ranged from 11 micrograms/l to 256
      micrograms/l (n = 1,930), and usage rates of iodized salt (> 20 PPM iodine
      content) in their households ranged from 3% to 82%. We concluded that severe
      iodine deficiency in 1992 was improved from moderate to mild severity a few years
      later by salt iodization. However, stronger official commitments and community
      participation are needed to improve the programme so that iodized salt will be
      made more widely available.

PMID- 11836922
TI  - Differences in blood pressure level and hypertension in three ethnic groups of
      northeastern India.
AB  - A cross sectional study on hypertension was done on 294 subjects aged 30 years
      and above. 150 households were selected randomly representing 50 households from
      each locality inhabited exclusively by the rural Mizos, indigenous rural Assamese
      and the tea-garden workers respectively, in the northeastern region of India.
      Blood pressure was measured by sphygmo-manometer in sitting posture. Anthro
      pometric measurements were taken using standard procedure for measuring height,
      weight, waist and hip girth. Information on age, sex, ethnicity, literacy,
      alcohol intake, smoking pattern, physical activity, occupation, amount of salt
      consumption was collected using a standard and pre-tested questionnaire.
      Significant differences were observed in both the systolic and diastolic blood
      pressure levels among the three different ethnic groups selected for this study
      (p < 0.0001). Multiple regression analyses indicated that in Mizos, age, waist
      circumference and alcohol intake were independently associated with increase in
      systolic blood pressure whereas smoking was found to be negatively associated
      with systolic blood pressure (R2 = 0.391, p < 0.001). Factors, which were the
      best predictors of diastolic blood pressure, were age and body mass index
      [(kg/m2) (R2 = 0.227, p < 0.001)]. In the rural Assamese population, the best
      predictors of systolic blood pressure were age and waist circumference (R2 =
      0.263, p = 0.018). For the diastolic blood pressure, age, alcohol intake and body
      mass index were important correlates (R2 = 0.131, p < 0.001). In the tea garden
      community, important predictors of systolic blood pressure were age, gender and
      marital status (R2 = 0.187, p < 0.001). On the other hand, age and alcohol intake
      were best predictors for diastolic blood pressure (R2 = 0.09, p < 0.001).

PMID- 11836925
TI  - Communicating health risks in the Pacific: scientific construct and cultural
      reality.
AB  - Health workers often communicate to people from a position of power rather than
      focusing on the needs of the receivers. This is usually clouded with jargon and
      the so-called principles of scientific accuracy. Often the use of science is to
      justify the health worker's position rather than to precipitate actions to
      promote health and achieve people's control over their lives. Communication
      involves a tripartite reciprocal interaction between the sender, receiver and the
      medium. This involves both science and art specific to the message, language,
      values and participants. If the ultimate purpose of communication is healthful
      action and community control, then scientificness of the explanations must be
      secondary. Therefore the art of getting the message across must be the priority
      rather than it being scientifically sound. This conflict is discussed in relation
      to experiences in the Pacific Islands. The communication of health risks in the
      Pacific involves the multi-tiered translation of scientific concepts and language
      into those of the target populations. The scientific concepts are usually
      occidental and need to be translated into vernacular worldviews and languages.
      Experiences in and examples from the Pacific have challenged the primacy of
      scientific explanations over the need to minimise health risks and increase of
      community control. For health promotion to succeed in multicultural and
      multilingual Pacific, New Zealand and Australia, the art and science of
      communicating health risks must be titrated against scientific explanations to
      appropriately and primarily promote health.

PMID- 11836924
TI  - Evaluation of a Philippine community based rehabilitation programme.
AB  - In 1991, the Philippine Department of Health implemented a Philippine Model of
      the World Health Organisation's Community Based Rehabilitation Programme
      initiative in pilot areas. The objective of this study was to explore whether,
      after seven years of operation, the Programme had actually been implemented as
      planned. The study was conducted in one pilot area in Rosario, La Union, a rural
      district of Luzon. The research used audit methodology to compare planned
      services with actual services. The main audit techniques used were record review,
      in-depth personal interview and focus group discussions. The study showed that
      such a programme, if properly organised and managed, can meet the needs of the
      people with disabilities who need rehabilitation. The Community Based
      Rehabilitation Programme represents a simple cost-effective approach for the
      delivery of disability prevention and rehabilitation services, particularly in
      rural areas that have little access to such services.

PMID- 11836926
TI  - Perceived oral health status, oral function and related behaviour among the
      patients of Behcet's disease.
AB  - The majority of patients with Behcet's disease (BD) suffers from oral ulcers. The
      aim of the present study was to survey self-rated oral health status, oral
      function, and oral health behaviour of patients with BD in eastern Japan.
      Subjects were 33 BD patients and 101 healthy individuals ranging in age from 20
      to 59 years. The survey was conducted using a self-administered questionnaire.
      The items of oral health in the questionnaire included subjective symptoms, self
      rated dental problems and oral health behaviour. We found that compared to the
      healthy subjects, BD patients experienced more severe physical limitations,
      mainly involving difficulty in pronouncing words (p < 0.01) and the pain of oral
      mucosa and gingival tissue caused by oral ulcers (p < 0.01). Based on the results
      of oral health behaviour, BD patients did not behave positively with regard to
      maintaining oral health including regular tooth brushing despite relatively
      higher risk of dental diseases that they face. The present results suggest that
      oral ulcers due to BD induced dental disorder such as the pain of gingiva, oral
      mucosa, and difficulty in the pronouncing of words. In spite of this, their oral
      health behaviour is not positive compared to the healthy subjects. Thus, the need
      to develop a more active pragramme for oral health education for patients with BD
      is indicated.

PMID- 11836927
TI  - UV light and oxidative damage of the skin.

PMID- 11836929
TI  - [3,5-Dinitrobenzoic acid anhydride as reagent for the characterization of drugs
      and for the activation of polarographically inactive compounds].
AB  - Drugs with primary or secondary amino groups react with 3,5-dinitrobenzoic acid
      anhydride under catalysis of pyridine derivatives almost quantitatively to yield
      the corresponding amides which are reducible at the dropping mercury electrode
      (DME). 3,5-Dinitrobenzoic acid will be separated by thin layer chromatography.
      The limit of detection by DPP is in the range of 10(-8) M. The electrode reaction
      is irreversible.

PMID- 11836928
TI  - Synthesis and biological activity of chiral tetrahydrofuranyl amino acids as
      building moieties of pamamycin analogues.
AB  - A new synthetic route to chiral tetrahydrofuranyl amino acids is described
      starting with D-glucose. The 17-step and a 20-step procedures, respectively,
      furnished compounds of the general formulas 1 and 2 mimicking the dimethylamino
      carboxylic acid part of pamamycin (3). In comparison with the absolute
      stereochemistry of 3 the acyclic compounds 1a-c and 2a-c are enantiomers. Despite
      of the presence of a dimethylamino function they showed neither antibacterial
      activity nor protonophoric effects on an artificial bilayer membrane suggesting
      that the macrodiolide ring of 3 forms an indispensable prerequisite for the known
      interaction of this antibiotic with biological systems.

PMID- 11836930
TI  - Determination of iron limiting values according to PH. EUR. using 1,3-dibromo-5,5
      dimethylhydantoin (DBH) instead of elemental bromine. Analytical methods of
      pharmacopoeias with DBH in respect to environmental and economical concern. Part
      8.
AB  - PH. EUR. 2002 uses elemental bromine performing iron limit tests for maleic acid
      (iron 5 ppm) and titanium dioxide (iron 200 ppm). 1,3-Dibromo-5,5
      dimethylhydantoin (DBH) can replace bromine water. For the iron limit test of
      maleic acid bivalent iron is oxidized to trivalent iron by bromine resp. DBH,
      because the unsaturated, in high concentration existing acid reacts substantially
      slower. On the other hand maleic acid removes the excess of bromine. The bromine
      oxidation for the iron limiting values of titanium dioxide according to the
      pharmacopoeia is not required. Metallic iron as well as ferrous salts are
      converted to trivalent iron, when the titanium test solution is prepared by
      boiling with concentrated sulphuric acid in the presence of anhydrous sodium
      sulphate.

PMID- 11836931
TI  - Effect of drug proportion and mixing time on the content uniformity of a low dose
      drug in a high shear mixer.
AB  - The purpose of this study was to investigate the effect of reducing drug
      proportion and mixing time on the content uniformity of a low dose drug.
      Buspirone hydrochloride was used as a model drug and was mixed with other
      ingredients in two different concentrations (0.5% w/w and 5% w/w) in a T. K.
      Fielder high shear mixer at a high impeller speed (522 rpm) and a high chopper
      speed (3600 rpm) up to 32 min. Samples were withdrawn from nine locations in the
      mixer at specific time points using a side-sampling thief probe. The final blends
      at 32 min were compressed using an instrumented tablet press. Tablets were
      sampled at the beginning, middle, and end of the compression run. The statistical
      results indicated that the drug proportion had a significant effect on the
      content uniformity of the powder blend and the corresponding tablets. For this
      study, the optimum time to mix the 0.5% w/w formulation was after 8 min while it
      was only 1 min for the 5% w/w formulation. The RSD of buspirone hydrochloride
      contents of tablets decreased as the compression run was toward its end.
      Uniformly mixed blends produced tablets that met the USP XXIV content uniformity
      requirements.

PMID- 11836936
TI  - Synthesis of novel thiol-reactive clenbuterol analogues.

PMID- 11836932
TI  - Pegnology: a review of PEG-ylated systems.
AB  - Polyethylene glycol conjugation or linking with the system is called PEGylation.
      Many novel drug systems are used for the delivery of drugs and bioactive
      substances to particular sites in a controlled or sustained manner, but various
      side effects or shortcomings restrict their use for the intended purpose. The
      shortcomings such as RES uptake, drug leakage, immunogenicity, stability,
      hemolytic toxicity etc. can generally be overcome by PEGylation of novel drug
      delivery systems such as liposomes, proteins, enzymes, drugs, nanoparticles etc.
      In this article the whole aspect of PEGylation starting from activation and
      derivatisation of poly (ethylene glycol) to the linking and designing of systems
      and their purification and characterization is discussed. The various properties
      of Pegylated systems are also discussed.

PMID- 11836933
TI  - Differences in the coalescence kinetics of fat emulsions in dependence on the
      amount of fat and age.
AB  - The destabilizing effect of calcium ions on emulsions was studied as a function
      of the age of the emulsions and the degree of emulsion dilution (2%, 0.2% an
      0.02% fat). Particle size measurements were performed both in the Coulter counter
      and a laser diffraction device equipped with PIDS technology. The data of both
      instruments showed a good correlation. zeta-Potential was determined by laser
      doppler anemometrie. The physical stability of the emulsions in 6 mmolar Calcium
      Chloride decreased with increasing dilution--despite the diminished rate of
      collision in diluted systems. In addition, and increased electrolyte sensitivity
      was observed with increasing age of the emulsions--despite enhanced electrostatic
      stabilization by an increased zeta-potential. Both effects were attributed to an
      increased binding of calcium ions per surface area of the droplets, i.e.
      increased ratio calcium ions to surface by dilution and increased binding by the
      increased charge of aged emulsions.

PMID- 11836934
TI  - Microbiological conversion of a beta- and gamma-eudesmol mixture by Rhizopus.
AB  - A mixture of beta- and gamma-eudesmols was microbiologically biotransformed by
      Rhizopus stolonifer ATCC 6227. Positions-2 and 3, in both substrates, proved to
      be accessible by hydroxylase enzyme. Four different metabolites were isolated and
      their structures were elucidated by different spectroscopic methods. The
      structures of these metabolites were established as eudesma-3-en-2 beta,11-diol;
      eudesma-4-en-3 beta,11-diol; eudesma-4(15)-en-2 beta,11-diol and eudesma-4(15)-en
      3 beta,11-diol.

PMID- 11836939
TI  - Isoflavans from Sphaerophysa salsula.

PMID- 11836935
TI  - From khellin to sodium cromoglycate--a tribute to the work of Dr. R. E. C.
      Altounyan (1922-1987).
AB  - Sodium cromoglycate, which was launched in 1968 by the British company Fisons for
      the treatment of allergies and asthma, was an absolute novelty in chemical,
      pharmacological as well as therapeutic respects. The khellin derivative meanwhile
      did not owe its discovery to the usual strategies for finding drugs. On the
      contrary, the protective effect of the substance was discovered in a self trial
      through systematic antigen-induced provocation tests of the medicinal doctor and
      allergic Roger Ernest Collingwood Altounyan (1922-1987). The only subsequently
      formed hypothesis of a mast cell stabilising effect of Sodium cromoglcycate did
      not prove to be valid for the search for similar or more effective substances. A
      further development of this drug class could not take place because of the lack
      of suitable pharmacological models.

PMID- 11836938
TI  - Neuropogonines A, B and C, new depsidon-type metabolites from Neuropogon sp., an
      Antarctic lichen.

PMID- 11836940
TI  - George Alan Jeffrey.

PMID- 11836941
TI  - Sumio Umezawa.

PMID- 11836937
TI  - Investigations on topical formulations of clomiphene citrate for treatment of HPV
      lesions.

PMID- 11836942
TI  - Structure and biological interactions of heparin and heparan sulfate.

PMID- 11836943
TI  - The chemistry of oligosaccharide ligands of selectins: significance for the
      development of new immunomodulatory medicines.

PMID- 11836945
TI  - Helicobacter pylori: a wolf in sheep's clothing: the glycotype families of
      Helicobacter pylori lipopolysaccharides expressing histo-blood groups: structure,
      biosynthesis, and role in pathogenesis.

PMID- 11836944
TI  - Sugar derivatives having sulfur in the ring.

PMID- 11836947
TI  - Applications of Raman spectroscopy to library heritage.
AB  - This work reports some different applications of Raman spectroscopy, a high
      sensitive non-destructive technique, to the conservation of Library Heritage. By
      Raman spectroscopy we were able to detect the chemical mechanisms leading to
      cellulose degradation, identifying the different functional groups formed during
      the paper ageing. This kind of information is fundamental to choose a suited
      restoration treatment. A second reported application is the identification of
      pigments used to decorate paper and parchments. We report some results obtained
      from analysis of a XV and a XIII century illuminations.

PMID- 11836946
TI  - Study of the vibrational spectrum of cuprorivaite.
AB  - In this research, after tracing a history of the pigment, the preparation and
      analysis of samples of Egyptian blue have been reported. The main reactions
      taking place during its preparation are indicated. X-ray diffractions show that,
      starting from mixtures of precursors with stoichiometric composition, the product
      is practically only cuprorivaite. The kind of flux and cristallinity of silica
      does not seem determining factors for the pigment formation. Infrared and Raman
      spectra and an assignment of the bands are reported. Impurities ascertained are
      discussed on the basis on the data available.

PMID- 11836948
TI  - Identification of different types of imperial age marble finds using instrumental
      chemical analysis and pattern recognition analysis.
AB  - A physical-chemical characterisation of several marbles frequently used in
      ancient times for artistic or decorative purposes was performed in support the
      work of historians and restorers. The data were obtained using several different
      types of instrumental chemical methods (Thermogravimetry, Differential Thermal
      Analysis, X-ray Diffractometry and ICP Plasma Emission Spectroscopy) and have
      been summarised in short tables. The data have already proved useful in the
      identification of a small number of finds (statues or architectonic elements)
      from Ancient Rome (Imperial Age, 2nd-3nd cent. A.D.) for the purpose of which
      also a well-known pattern recognition analysis software package was used for data
      processing. In practice, the research showed that an organised set of chemical
      data obtained using several modern instrumental methods can provide a valid basis
      for the reasonably rapid and reliable identification of the type of marble used
      to make artistic artifacts that have not yet been subjected to typological study.

PMID- 11836949
TI  - Characterisation of fatty acids in drying oils used in paintings on canvas by GC
      and GC-MS analysis.
AB  - Of the various binding media used in paintings, this work examines drying oils.
      During the initial phase of polymerisation and the progressive ageing process,
      the fraction of unsaturated and polyunsaturated fatty acids undergoes various
      changes (reticulation, oxidation, etc.), that give rise to characteristic
      compounds. Within a broader research project, aimed at the characterisation of
      binding media, a preliminary study was made of the ageing process of linseed oil.
      In this regard, linseed oil was spread on a glass or canvas support and then
      dried in the open air. The ageing of the spread linseed oil was monitored by
      taking samples of the material at regular intervals. After the fatty acids had
      changed into methylesters, the samples were analysed by gas chromatography (GC)
      and gas chromatography-mass spectrometry (GC-MS). The results obtained have been
      reported as a ratio between the areas of the chromatographic peaks of the
      different fatty acids found.

PMID- 11836951
TI  - Effect of fluorinated groups on photooxidative stability of polymeric protectives
      applied on marble.
AB  - Some new protective copolymers and a commercial one have been tested on Candoglia
      marble, a very low porosity stone. Two of the polymers contained a partially
      fluorinated methacrylic monomer, 2,2,2 trifluoro ethyl methacrylate (TFEMA), in
      combination with either an acrylic, methyl acrylate (MA) or a vinyl ether, n
      butyl vinyl ether (n-BVE) unit. Two copolymers, ethyl methacrylate/n-butyl vinyl
      ether and ethyl methacrylate (EMA)/methyl acrylate (Paraloid B72), were non
      fluorinated and similar in compositions and molar ratio. The aim of the work is
      to test the copolymers and compare the performances of fluorinated new polymers
      with the non fluorinated one and with the largely used commercial product. The
      results obtained demonstrate that the introduction, even in limited amounts, of
      fluorine atoms in the side ester groups of methacrylic type polymers really
      improves their protective effect and the durability of the stone treatments. The
      best results were obtained with the copolymer TFEM/MA which is the fluorinated
      homologous of Paraloid B72.

PMID- 11836950
TI  - Application of gas chromatography-mass spectrometry analysis to the study of
      works of art: paint media identification in polychrome multi-material sculptures.
AB  - A new gas chromatographic-mass spectrometric procedure for characterizing both
      drying oils and proteinaceous binders in samples of painted artworks has been
      developed. Furthermore, a new analytical procedure for analysis of polysaccharide
      materials through identification of the monosaccharide constituents is proposed.
      The methods have been applied to characterizing binding media of the different
      layers of the polychrome surface in the multi-material sculptures from the
      sanctuary of Santa Maria delle Grazie in Mantova, Italy. It was found that animal
      glue was the main binder in the priming layer of all statues, whereas more
      complex mixtures were used in the paint layers. Generally, a drying oil was
      present, most often linseed oil alone or in combination with other organic
      binders.

PMID- 11836954
TI  - The stone decay of monuments in relation to atmospheric environment.
AB  - In order to explain why different forms of decay are present on a building facade
      some samples were taken from different areas of many monuments. Macroscopic
      observations of the forms of decay were correlated with quantitative analytical
      data in order to build up a simple model which was able to explain in a general
      way the decay phenomena. This simplified model was tested on several Venetian
      monuments and the features visible on stone surfaces correspond to different
      degree of deterioration. The quantitative analytical data were associated with
      the different forms of decay, which were defined as white washing, dirt
      accumulation and dirt washing. The results obtained showed that the features
      visible on stone surfaces corresponded to different degree of deterioration and
      the sulphate formation is greatest in the black dendrite-shaped crusts which are
      generally formed at the interface between the white washing areas and the
      sheltered ones, which were defined as dirt washing area.

PMID- 11836953
TI  - Monitoring of atmospheric pollutants by passive sampling for the protection of
      historic buildings and monuments.
AB  - When considering the various possibilities to assess the effects of SO2 and NO2
      on historic buildings and monuments, a distinction can be made according to the
      completeness of the scope of the assessment itself. A first approach can be
      limited to gathering data as they become available through the official bodies
      established under air quality legislation. This approach is based on a single
      point measurement where a "general purpose" monitoring station is located, often
      quite far from the monument to protect and often without investigating local and
      temporal variations. A more comprehensive assessment should include a
      generalisation that covers the territory. This can be made on the basis of the
      knowledge of the spatial distribution of concentrations and the knowledge of the
      causes of air pollution. Passive samplers allow the measurement of air quality in
      numerous sites and to assess the pollutant spatial distribution over a large area
      with a high resolution. As an application of the method, the spatial distribution
      of SO2 and NO2 in the city of Siracusa, Sicily, Italy, has been studied to
      identify areas of high deposition fluxes in relation to the protection of
      buildings and monuments of the historic centre.

PMID- 11836952
TI  - Copper resinate: preparation, characterisation and study of degradation.
AB  - This paper describes a method for the synthesis of Copper Resinate, which
      disappeared from artists' palettes in the eighteenth century. This was carried
      out by interpreting ancient recipes following a scientific approach. Its
      characterisation using Fourier Transform-Infrared Spectrometry and Gas
      Chromatography-Mass Spectrometry demonstrated that it is a mixture containing
      copper and oxidised abietic acids, mainly dehydroabietic and 7-oxo-dehydroabietic
      acids, formed during the preparation of the pigment and the curing of the paint
      layer. The composition of copper resinate paint layers, artificially aged by U.V.
      irradiation at 365 nm (UV), heating (T), and exposed to atmospheric pollutants
      (NOX) in a climatic chamber, was investigated. The combination of irradiation and
      temperature produced a change in colour along with a significant increase in the
      recovered amount of 7-oxo-dehydroabietic acid. The identification of copper
      resinate in a sample from an old painting should be related to the presence of
      the following resin compounds which are stable in the ageing process:
      dehydroabietic and 7-oxo-dehydroabietic acid pimaradienic acids. Photo-oxidation
      of the resin acids co-ordinated with copper seem to be the most probable decay
      mechanism responsible for the colour change in the pigment.

PMID- 11836956
TI  - Microbial growth and air pollution in carbonate rock weathering. Preliminary
      results of a in situ experimental study.
AB  - Preliminary results on limestone weathering caused by air pollution and microbial
      colonization are presented in this study. Outdoor exposure experimental assays
      were performed on Scaglia limestone samples. Samples were exposed in two areas in
      Perugia (Italy) that differ for degree of urban air pollution. At different times
      of exposure, ranging from 1 to 12 months, microbial contamination and textural
      modifications of sampled surfaces were evaluated by microbiological procedures, X
      ray diffraction, and scanning electron microscopy. After one year of exposure a
      significant fungal colonization and the presence of weathering products (i.e.
      gypsum) were detected on sampled surfaces.

PMID- 11836955
TI  - The wall paintings in the Oratorio of San Giovanni Battista in Urbino: a study
      finalized to a correct conservation project.
AB  - The walls of the Oratorio of San Giovanni Battista in Urbino are decorated with
      outstanding mural paintings dating back to the 15th century. Due to degradation
      processes that have occurred in the past years, such paintings require a
      conservative restoration project. In order to evaluate reasons of the decay, some
      scientific studies have been performed. They consist of macroscopic observations
      and chemical (EDS), morphological (SEM) and mineralogical (XRD) analyses of
      samples both from the original preparatory layers under the painted layers and
      from the restored plasters at the surbase of the wall. In addition, environmental
      studies have been performed to verify microclimatic conditions of the church in
      which the mural paintings are located. Finally, a conservative restoration
      project was proposed.

PMID- 11836957
TI  - Atypical coloration of plaster in renaissance frescoes.
AB  - The Baptistery of Castiglione Olona (Varese, Italy), frescoed by Masolino da
      Panicale at the beginning of the 14th Century, is currently under restoration. On
      this occasion its state of preservation was investigated, in order to plan a
      correct intervention. During the sampling, an interesting phenomenon was pointed
      out, i.e. a wide rose coloration on the plasters of the interior northern and
      western walls. In order to clarify the nature of the alteration, a sampling was
      undertaken both for a chemical-mineralogical characterization of plasters (XRD,
      SEM-EDX, FTIR) and to detect the presence of biodeteriogens.

PMID- 11836958
TI  - Neolithic ceramic findings from western Sicily. Chemical-physical and
      mineralogical characterization.
AB  - This paper presents the results of a study that is part of a wider research
      program regarding the knowledge of the initial living phases of Sicilian
      agricultural and pastoral societies. Three ceramic samples attributed to the
      medium initial Neolithic (NEO1 and NEO2) and to the first neolithic (NEO3),
      recovered in two different archaeological sites of the western Sicily, have been
      analysed. Chemical, mineralogical and spectroscopic data point out a similarity
      between NEO1 and NEO3 samples; compositional and morphological differences
      instead have been observed in the NEO2 sample. The firing temperatures of the
      samples have been estimated by Mossbauer spectroscopy; they are lower than 500
      degrees C for the samples NEO1 and NEO3, and about 700 degrees C for NEO2.

PMID- 11836959
TI  - Evaluation of barium hydroxide treatment efficacy on a dolomitic marble.
AB  - The Arch of Peace, by Luigi Cagnola, is one of the most famous neoclassical
      monuments in Milan. It has been subjected to conservative intervention in 1998.
      In the present paper the efficacy of the consolidation by means of barium
      hydroxide has been evaluated. The stone material showed severe degradation
      phenomena as: erosion, pulverisation, exfoliation. The analytical data acquired
      through X-ray diffraction (XRD), infrared spectrophotometry (FTIR) and scanning
      electron microscopy (SEM-EDX), allowed to compare the conditions of stone before
      and after the treatment with barium hydroxide. The presence of barium has been
      put in evidence mainly on the surface as barium sulphate, whereas barium is only
      sporadically present within the thickness of the decayed material. The treatment
      was judged not satisfying and its inefficacy is, most probably, due to a not
      suitable cleaning procedure carried out before the consolidation.

PMID- 11836960
TI  - A key factor in modern protection of historic buildings: the assessment of
      penetration of water-repellent polymers into porous stone-materials.
AB  - From the 1960s on, the conservation of monuments and stone masonry has witnessed
      an increasing use of polymeric products during restoration interventions. Actual
      penetration depths reached by different polymers within the porous stone matrix
      are supposed to be key factors in determining the efficacy of the treatments
      themselves (besides, of course, the chemical-mineralogical nature of the stone
      and the chemical-physical characteristics of the various polymers). This work
      presents some preliminary results obtained on specimens of Noto calcarenite
      treated with various polymeric protective products. Samples were investigated
      with direct analytical methods (micro-ATR spectroscopy, SEM) in order to assess
      penetration depths reached by polymers inside the stone while reducing to a
      minimum the necessary manipulation of specimens. The obtained results highlighted
      the following trend in penetration depths for the various products tested:
      siloxane product > partially fluorinated acrylic resin > acrylic resin. Moreover,
      data obtained allowed to establish direct correlation between long term efficacy
      of products and relative penetration depths.

PMID- 11836963
TI  - Interview with John G. King, FACHE, advisor, Legacy Health System, Portland,
      Oregon. Interview by Kyle L. Grazier.

PMID- 11836962
TI  - The relationship between hospital unit culture and nurses' quality of work life.
AB  - Turnover rates for hospital nurses have been increasing in recent years, which is
      partially a result of increasing pressure on nurses from higher productivity
      expectations in a managed care environment. Improving nurse retention is a
      difficult challenge to managers since the bureaucratic cultural norm of
      hospitals, with its hierarchical structures, rules, and regulations, and heavy
      emphasis on measurement of outcomes and costs, may not be the culture most
      conducive to enhancing nurses' job satisfaction and commitment. Accordingly, this
      study investigates the relationships between unit organizational culture and
      several important job-related variables for nurse retention in the labor and
      delivery units of seven hospitals. Data analysis shows that unit organizational
      culture does affect nurses' quality of work life factors and that human relations
      cultural values are positively related to organizational commitment, job
      involvement, empowerment, and job satisfaction, and negatively related to intent
      to turnover. These findings suggest that although increasing recruitment of
      nurses and improved compensation and benefits strategies may offset hospital
      nurse shortages in the short term, improving quality of work life may be a more
      practical and long-term approach to improving hospital nurse retention.

PMID- 11836961
TI  - Characterisation of pigments and corrosion patinas by means of micro-Raman
      spectroscopy.
AB  - New applications of micro-Raman spectroscopy are presented here for the
      investigation of colouring agents in a wax model of plant and of corrosion
      products on metal artworks. A late 1700 wax model of Camellia japonica L. was
      studied in order to characterise the nature of white, red and green colours of
      petals and leaves. White and red colours of petals were identified as pigments of
      baryte and a mixture of cinnabar and carmine lake, respectively. Fragments taken
      from leaves with different green hues were also studied; only yellow grains were
      isolated in this case which were identified as orpiment and yellow chrome. The
      applicability of micro-Raman spectroscopy to the study of corrosion products on
      metal objects is presented here for iron archaeological artefacts and for lead
      samples taken from the cupolas of the Consolata Sancturay in Turin. Analysis of
      blackish and reddish corrosion patinas entirely covering the archaeological iron
      objects led to the identification of magnetite and maghemite, goethite and
      lepidocrocite, respectively. As to lead fragments, the main corrosion product was
      lead sulphate, and minor amounts of lead carbonate, nitrate and oxide (litharge)
      were also found.

PMID- 11836964
TI  - Urban U.S. hospitals and the mission to provide HIV-related services: changes and
      correlates.
AB  - In 1988, the vast majority of urban U.S. hospitals (84 percent) exhibited some
      formal response to the demand for HIV-related services. Despite the fact that HIV
      related care is now normative in many respects and the demand for inpatient care
      has decreased, nearly half of hospitals surveyed in 1997 (42 percent) report no
      formalized service provision, suggesting a heightened distinction between
      hospitals in terms of their varying commitments to providing HIV-related
      services. Certain organizational variables (such as ownership, size, system
      affiliation, and stigmatized services and post-acute care services indices) were
      connected to HIV-related services provision. When the sample was controlled for
      other variables, the study found that changes in teaching status, changes in bed
      size, and changes in post-acute services from 1988 to 1997 did influence the
      provision of HIV-related services. Despite significant changes over the study
      period in the treatment of persons living with HIV/AIDS, and structural changes
      in the delivery of U.S. healthcare, the organizational-level predictors of HIV
      related service provision have remained remarkably stable among U.S. hospitals in
      urban settings. These data also suggest that organizational missions consistent
      with serving indigent and socially marginalized populations continue to influence
      the ways that the pluralistic U.S. hospital system organizes HIV-related care.

PMID- 11836965
TI  - Measuring comparative hospital performance.
AB  - Leading healthcare provider organizations now use a "balanced scorecard" of
      performance measures, expanding information reviewed at the governance level to
      include financial, customer, and internal performance information, as well as
      providing an opportunity to learn and grow to provide better strategic guidance.
      The approach, successfully used by other industries, uses competitor data and
      benchmarks to identify opportunities for improved mission achievement. This
      article evaluates one set of nine multidimensional hospital performance measures
      derived from Medicare reports (cash flow, asset turnover, mortality,
      complications, length of inpatient stay, cost per case, occupancy, change in
      occupancy, and percent of revenue from outpatient care). The study examines the
      content validity, reliability and sensitivity, validity of comparison, and
      independence and concludes that seven of the nine measures (all but the two
      occupancy measures) represent a potentially useful set for evaluating most U.S.
      hospitals. This set reflects correctable differences in performance between
      hospitals serving similar populations, that is, the measures reflect relative
      performance and identify opportunities to make the organization more successful.

PMID- 11836966
TI  - Computer simulation: a methodology to improve the efficiency in the Brooke Army
      Medical Center Family Care Clinic.

PMID- 11836967
TI  - The roles of the senior-level executive.

PMID- 11836968
TI  - Organ procurement 1999-2000: how is Hawaii doing?
AB  - With the advent of The Final Rule, the state of Hawaii should have potential
      organ donor identification and referral rates of 100%. However, a retrospective
      chart review of 4,697 deaths in 1999 and 4,730 deaths in 2000, revealed
      identification rates of 80% and 84%, and referral rates of 53% and 71%,
      respectively. Proper recognition and referral of all potential donors is
      essential to bridging the enormous gap between the supply of organs and its
      demand.

PMID- 11836969
TI  - A systematic approach to provider based disability management.
AB  - Tacit within the treatment goals of every workers' compensation case is timely
      return of the worker to pre-injury status. Assigned disability status must truly
      reflect the extent of medical impairment and functional limitations affecting
      return to his/her customary job. Permanent Partial Disability (PPD) awards with
      associated legal involvement are widely acknowledged as a major cost driver
      within the Workers' Compensation system. Medical providers are encouraged to
      become pro-active disability management specialists for each workers'
      compensation case. Provider review of critical process checkpoints and
      integration of medical treatment with disability guidelines maximize benefits to
      the injured employee and the employer. This in turn enhances providers' control
      of patient care with less emphasis on external case managers.

PMID- 11836971
TI  - Role of standardized patients in medical education.
AB  - Standardized patients are volunteers from the community who participate actively
      in the teaching and evaluation of our future physicians. The SP program augments
      medical student learning in both clinical and basic sciences by providing
      opportunities to practice on patients who are available and willing to be
      examined. SPs allow "teachable moments" to be created, rather than waited for. SP
      based examinations are the most reliable and standardized methods for performance
      based assessment of bedside clinical skills. The problem-based-learning (PBL)
      approach to medical education at JABSOM is designed to foster self-directed
      learning, interpersonal skills and early hands-on clinical experiences. JABSOM SP
      experiences are integrated within the PBL curriculum. The CCS and SPs are now
      vital components of the JABSOM educational model.

PMID- 11836970
TI  - A 14-year-old girl with refractory seizures.

PMID- 11836972
TI  - Etiologic research on lung cancer in Hawaii: the roles of smoking, phytochemicals
      and metabolic genes.

PMID- 11836974
TI  - Effectiveness of clozapine in neuroleptic-resistant schizophrenia: clinical
      response and plasma concentrations.
AB  - OBJECTIVE: To assess the relation between plasma concentrations of clozapine and
      its 2 main metabolites desmethyl clozapine and clozapine N-oxide, and clinical
      change in a sample of inpatients with schizophrenia who were resistant to
      conventional neuroleptics. METHOD: Thirty-seven patients (27 men and 10 women,
      mean age 34.8 yr) with treatment-resistant schizophrenia were treated with
      clozapine for 18 weeks; dosage was adjusted according to clinical response, and
      plasma concentrations of clozapine and of its metabolites were measured weekly by
      high-performance liquid chromatography. Clinical status was also assessed weekly
      with the Positive and Negative Syndrome Scale (PANSS). Patients were considered
      "responsive" if they showed at least a 20% improvement over their baseline PANSS
      ratings. RESULTS: The mean endpoint clozapine dosage was 486.5 mg/day. There was
      a significant correlation between the daily dosage of clozapine and the plasma
      levels of clozapine and of its metabolites (p < 0.05). There was no correlation
      between the clozapine plasma level and the percent improvement on the PANSS.
      Clozapine plasma levels were not significantly different between those who
      responded to clozapine (n = 19) and those who did not (n = 18) and were not
      significantly different between patients who smoked (n = 28) and those who did
      not (n = 9). Receiver operating characteristic (ROC) curve analysis determined
      the plasma level threshold (above which a better clinical response was obtained)
      to be 550 ng/mL. Using the total of plasma levels of clozapine and its
      metabolites did not lead to a better sensitivity and specificity. CONCLUSIONS:
      Our calculated plasma clozapine threshold was higher than that reported by
      others, but this may be related to the severity of symptoms of our patient
      sample. Monitoring plasma rates remains a useful tool, together with clinical
      evaluation, to establish the clozapine dosage for an optimum benefit-risk ratio.

PMID- 11836975
TI  - Quantitative EEG amplitude across REM sleep periods in depression: preliminary
      report.
AB  - OBJECTIVE: To determine if there are significant differences in the temporal
      organization of rapid eye movement (REM) sleep microarchitecture between healthy
      controls and outpatients with major depressive disorder (MDD). METHODS: Forty age
      matched subjects, 20 men and 20 women, half with MDD, were selected from an
      archive of sleep electroencephalography (EEG) data collected under identical
      conditions. Each participant spent 2 consecutive nights in the Sleep Study Unit
      of the University of Texas Southwestern Medical Center at Dallas, the first of
      which served as adaptation. The average amplitude in each of 5 conventional EEG
      frequency bands was computed for each REM period across the second night. Data
      were then coded for group and sex. RESULTS: Aside from REM latency, none of the
      key sleep macroarchitectural variables differentiated MDD patients from controls.
      REM latency was longest in men with MDD. Sleep microarchitecture, however, did
      show a number of between-group differences. In general, slower frequencies
      declined across REM periods, with a significant REM period effect for delta,
      theta and alpha amplitude. Group x sex interactions were also obtained for theta
      and alpha. Beta activity showed a unique temporal profile in each group,
      supported by a significant REM period x group x sex interaction. In addition, the
      temporal change in theta amplitude across REM periods was most striking in women
      with MDD. CONCLUSIONS: This study suggests that, like during non-REM sleep, EEG
      amplitude shows a systematic temporal change over successive REM sleep periods
      and also shows elements that are both disease- and sex-dependent.

PMID- 11836976
TI  - Low-dose dexamethasone challenge in women with atypical major depression: pilot
      study.
AB  - OBJECTIVE: To examine if atypical depression may be associated with
      hypersuppression of the hypothalamic-pituitary-adrenal (HPA) axis. METHOD: Eight
      women with atypical major depression and 11 controls with no history of
      psychiatric illness, matched on age and body mass index, were challenged with low
      dose dexamethasone (0.25 mg and 0.50 mg in random order and 1 week apart).
      Dexamethasone was self administered at 11 pm, and plasma cortisol samples were
      drawn at 8 am and 3 pm on the following day. RESULTS: After the 0.50-mg
      dexamethasone challenge, mean suppression of morning cortisol was significantly
      greater in patients with atypical depression (91.9%, standard deviation [SD]
      6.8%) than in the controls (78.3%, SD 10.7%; p < 0.01). CONCLUSION: These
      preliminary data add to the growing body of literature that suggests atypical
      depression, in contrast to classic melancholia, may be associated with
      exaggerated negative feedback regulation of the HPA axis.

PMID- 11836977
TI  - Is cabergoline a better drug to inhibit lactation in patients with psychotic
      symptoms?

PMID- 11836980
TI  - Eye catching?
AB  - Decontamination has moved into the top ranks of healthcare issues. In this
      article, Frank Waller highlights the need for strict adherence to decontamination
      and sterilisation procedures at all perioperative levels. He demonstrates how
      apparently minor operations can have serious consequences for both the patient
      and for perioperative staff where decontamination and sterilisation are
      inadequate.

PMID- 11836978
TI  - Neuroprotective effects of antidepressant and mood stabilizing drugs.

PMID- 11836979
TI  - Should thyroid replacement therapy be considered for patients with treatment
      refractory depression?

PMID- 11836973
TI  - Estrogenic modulation of brain activity: implications for schizophrenia and
      Parkinson's disease.
AB  - Evidence suggests the estrogens may play a role in various mental and
      neurodegenerative diseases. We review the evidence implicating estradiol in
      schizophrenia and Parkinson's disease. Epidemiologic and clinical studies on the
      effects of estrogens in schizophrenia are surveyed, and animal studies and in
      vitro models of the modulatory effects of estrogens on neurotransmitters
      associated with schizophrenia (i.e., dopamine, serotonin, glutamate) are
      reviewed. Epidemiologic and clinical data suggesting a role for estrogens in
      Parkinson's disease and in vivo and in vitro models demonstrating neuroprotective
      effects of estrogens are then examined. Despite the numerous animal studies on
      the effects of estrogens in the brain, clinical data are sparse and often
      contradictory. Compounds with more specific and potent estrogenic activity in the
      brain are required to further research efforts in this area. Possible candidates
      are the selective estrogen receptor modulators (SERMs), whose agonist or
      antagonist properties depend on the target tissue. The effects of various SERMs
      in the brain are reviewed, and our novel findings on the effects of SERMs on 5
      HT2A receptors in the rat cortex and nucleus accumbens are presented. We suggest
      that drugs with estrogenic activity in the brain may have therapeutic potential,
      either by modulating brain neurotransmission or through neuroprotective activity.

PMID- 11836983
TI  - Instrument reprocessing in theatres. Drivers for change.
AB  - It is well known that long-term exposure to chemical disinfectants can have
      adverse effects on an individual, and can even result in ill health requiring
      premature retirement. Jim Miller highlights some of the dangers of chemical
      disinfectants and reports on the relative merits of newer technologies, including
      low temperature hydrogen peroxide.

PMID- 11836982
TI  - Postoperative nausea and vomiting in the perioperative setting.
AB  - Postoperative nausea and vomiting (PONV) is reported to occur in up to 92% of
      surgical cases. In this article, Agnes Arnold defines the terms, identifies a
      range of therapies and risk factors, examines the dangers and discusses the
      management of PONV. The article was originally produced as a study for ENB 183.

PMID- 11836981
TI  - Hepatitis C in perioperative practice.
AB  - This is the second of a series of three articles which won the Alison Bell
      Writer's Award this year. Maureen Dyke won second prize for this article, which
      looks at nurses' knowledge and appreciation of the dangers of the various
      hepatitis infections. The Writer's Award is sponsored by NATN and Regent Medical.

PMID- 11836984
TI  - Making meetings effective.
AB  - This is the last in the current series of articles considering various elements
      of effective management. Fiona Westwood has already looked at managing conflict,
      influencing people and doing deals. This article looks at one of the major causes
      of frustration for any organisation--the amount of time people spend in meetings
      and the limited value that such time investment produces.

PMID- 11836985
TI  - New job--no problem!

PMID- 11836986
TI  - [Diagnosis and surgical strategy in injuries of the heart and pericardium].
AB  - Results of the emergency diagnosis and surgical treatment of wounds of the heart
      and pericardium were summed up in 207 wounded during twenty years of work. It was
      found that injuries of the heart and pericardium were diagnosed in 42% of cases
      according to clinical symptoms, while emergency thoracotomy during the first
      minutes after admission to the surgical hospital was performed in 55-60% of
      wounded to the heart. About half wounded at the moment of admission to the
      hospital were at the state of relative stabilization of hemodynamic indices and
      had no clinical symptoms of wounds to the heart. In this group of patients
      injuries of the heart and pericardium were diagnosed on the basis of additional
      investigations, extrapleural pericardiotomy (fenestration of the pericardium)
      being most reliable. The results of treatment of wounded to the heart can be
      improved at the expense of acute surgical strategy which is determined by the
      stable state of the wounded, character of the myocardium injury and associated
      wounds.

PMID- 11836987
TI  - [State of central hemodynamics in traumatic disease].
AB  - The state of central hemodynamics was determined by the method of integral
      rheography of the body in 389 patients with severe combined traumas admitted to
      the clinic of field surgery of the Medical Military Academy. Under study was the
      dependence of the main indices of hemodynamics on severity of the state and
      character of the trauma. Changes to the parameters of hemodynamics in patients
      with sharply pronounced insufficiency of circulation were studied. It was shown
      that one of its mechanisms was an impairment of intrasystemic relationships
      between the minute volume and the forming indices: stroke output, heart rate,
      work of the left ventricle. The decisive rule was developed for the diagnosis of
      a small cardiac output.

PMID- 11836988
TI  - [Metabolic bases of the pathogenesis of severe multiple trauma].
AB  - Under analysis there were data of hormonal activity of the hypothalamo-hypohysis
      adrenocortical system and the incretory apparatus of the pancreas, metabolism (of
      proteins, lipids, carbohydrates) and concentration of microelements (iron, zinc),
      lipid peroxidation (content of malonic dialdehyde and diene conjugates, on the
      one hand, and total oxidative activity of blood, superoxide dismutase (SOD),
      ceruloplasmin, catalase, SH-group, on the other hand) and results of its
      therapeutic correction (with superoxide dismutase, ionole, extracorporeal laser
      irradiation and laser irradiation of the wounds), content of the inflammatory
      reaction markers (tumor necrosis factor and IL-1) in patients with a severe
      combined trauma in the dynamics of traumatic disease. The results obtained and
      literature data allow a conclusion to be made that the basis of metabolic changes
      in severe combined traumas are formed by a developing adaptation reaction of
      organism immediately after trauma integrated with the systemic aseptic
      inflammatory response caused by vast necrosis of tissues, hypo- and reperfusion
      processes. The intensity of these reactions depends on severity of the trauma,
      determines its clinical course and outcome. The therapeutic correction of higher
      activity of the lipid peroxidation system (caused by a systemic inflammatory
      response) ionol, extracorporeal laser irradiation of blood, laser therapy of the
      wounds increase the antioxidative volume of blood and decrease the production of
      lipid peroxidation. Early intrabronchial instillation of homogenic SOD increases
      the total antioxidative activity, the level of SOD and catalase, decreases the
      content of malonic dialdehyde in the sediment of broncho-alveolar lavage and in
      blood.

PMID- 11836989
TI  - [Endotoxicosis in severe multiple trauma].
AB  - The article touches upon the practical significance of methods of extracorporeal
      detoxication, pathogenesis of endotoxicosis, phases of its development. An
      analysis of data was made concerning treatment of 98 wounded and patients having
      injuries of three and more anatomical areas and who were in severe and critically
      severe states. Practical conclusions were made determining the expediency of
      using the methods of extracoprporeal detoxication in traumatic disease, special
      attention being given to optimization of functioning the detoxicating systems of
      organism.

PMID- 11836990
TI  - [Elena Vasil'evna Usol'tseva (1898-1993)].

PMID- 11836991
TI  - [In commemoration of the centenary of the department of hospital surgery of St.
      Petersburg I. P. Pavlov Medical University].

PMID- 11836992
TI  - [Endoscopic mechanical lithotripsy in the treatment of choledocholithiasis].
AB  - The method of endoscopic intraduct cleavage of calculi was used in 78 patients
      from 19 to 88 years of age. History of operations on bile ducts had 35 of them,
      laparoscopic cholecystectomy was performed in 43 patients after the endoscopic
      sanitation of the bile ducts. Three cases are described as illustration.

PMID- 11836993
TI  - [Indices of chronic intravascular hemolysis in patients with different prosthetic
      heart valves in long-term follow-up].
AB  - An examination of 153 patients with valve replacement was performed at late
      stages of (6.8 +/- 0.2) years, in 84 patients the mitral valve replacement (MVR)
      was fulfilled, in 64--the aortic replacement (AVR) and in 5--two valve
      replacement were performed. Higher indices of hemolysis were noted in patients
      with AVR, in cases of two valve replacement and in patients with the paravascular
      fistula. The lowest indices of hemolysis take place in patients with bileaflet
      prostheses (MEDING/CarboMedics, St. Jude Medical), especially in patients with
      AVR. The complications of intravascular hemolysis are: cholelithiasis, anemia,
      hemosiderosis of the kidneys, sideropenia. The timely diagnosis, treatment and
      prophylactics are necessary to prevent these complications.

PMID- 11836994
TI  - [Turbidimetric express method in the assessment of the hemostasis parameters in
      patients with prosthetic bileaflet heart valves].
AB  - Thirty patients of medium (47 +/- 3) years of age with prosthetic bileaflet heart
      valves without any specific complications of the I-II functional classes and with
      the postoperative period after mitral (11) and aortal (19) valve replacements
      during (2.52 +/- 0.48) years were studied. The defects of coagulation and
      fibrinolytic systems were found in 9 patients with high prothrombin index (93.21
      +/- 9.8)% and low INR (0.9-1.7). The activation of fibrinolysis, low platelets,
      hypofibrinogenemia, D-dimer which are the risk factors of thrombogenic
      complications were found in these patients. The updated turbo-dynamic express
      method which helps to activate fibrinolysis in short terms and to make its
      correction is proposed.

PMID- 11836995
TI  - [Intracardiac hemodynamics after closure of atrial septal defects with the
      endovascular device, Amplatzer septal occluder].
AB  - Changed size and forms of the right and left ventricles of the heart and
      intraventricular hemodynamics were studied in 5 patients after closing the
      defects of the interventricular septum with an intravascular device. It was found
      that after occlusion of the defects by the safe and atraumatic endovascular
      device the right ventricular myocardium of the heart relaxed, the stroke index
      became less, the ejection fraction became greater, the diastolic diameter of the
      right ventricle decreased, and of the left ventricle increased. The indices of
      the regional contraction function of the tri-cuspid and output sectors of the
      input part and external and pulmonary output sectors of the right ventricle were
      found to normalize.

PMID- 11836996
TI  - [New methods in angiocardiographic diagnosis of arrhythmogenic dysplasia of the
      right ventricle].
AB  - Arrhythmogenic dysplasia of the right ventricle (ADRV) is a congenital pathology
      of the heart resulting in the appearance of ventricular tachycardia that
      considerably increases risk of sudden death in young people. Up to now, however,
      the diagnostic criteria of this pathology have not been completely developed. An
      original method was used to study specific features of the regional contractile
      function (RCF) of the right ventricle and its diagnostic potentials in ADRV. The
      regional contractility of one of the right ventricle sectors was proved to
      decrease more than twice which corresponds to localization of additional
      conductive ways detected during the endo-electrophysiological examination of the
      heart. Changed indices of RCF should be referred to "great" angiographic criteria
      of diagnostics of ADRV.

PMID- 11836997
TI  - [Possibility of angiogenesis stimulation in ischemia by embryonic human brain
      tissue (initial experimental results)].
AB  - The article proves the presence of angiogenic activity of the original specimen
      of biological genesis obtained from the embryogenic human brain tissue. The
      investigation was carried out on ischemia models of the rat's myocardium and hind
      limb.

PMID- 11836998
TI  - [Transplantation of embryonic myocardium in animal experiments].
AB  - The work presents the results of experimental transplantation of a not-divided
      embryonic myocardium culture into the mesentery of the adult rats' intestine for
      the terms of about 30 days. The influence of Cimitidine--cardiolen on the
      development of this culture was investigated. The grafts were shown to be taken
      and to function well and the use of cardiolen reliably improves the development
      of the culture.

PMID- 11836999
TI  - [Effects of implantation technique on hydrodynamic and biomechanical
      characteristics of stentless aortic valve bioprostheses in experiments].
AB  - A comparative analysis of experiments with biomechanics and hydrodynamic
      stentless xenografts implanted into the subcoronary position with completely (n =
      7) and partially (n = 7) scalloped sinuses was made. The implantation was
      performed into the human aortic root complexes in vitro. Factors of the influence
      on biomechanical and hydrodynamic performances of xenografts before and after
      implantation have been established. Subcoronary implantation of stentless
      bioprostheses with the completely scalloped sinuses proved to result in better
      flow and biomechanical characteristics than the implantation technique with the
      saved noncoronary sinus.

PMID- 11837000
TI  - [Experience in the use and comparative assessment of the effectiveness of
      crystalloid and blood cardioplegia].
AB  - Due to an increasing attention to questions of adequate protection of the
      myocardium and widely spread use of the method of blood cardioplegia the authors
      have made a comparative analysis of effectiveness of using 2 methods of
      cardioplegia--pharmacocrystalloid and cool blood antegrade cardioplegia: 34
      patients were operated upon under conditions of extracorporeal blood circulation
      for aortic and mitral valve replacement. A comparison was made of 17 patients
      with intermittent antegrade cool crystalloid cardioplegia (group 1) and 17
      patients with intermittent antegrade cold blood cardioplegia (group II). The
      results have shown that intermittent antegrade cool blood cardioplegia is a safe
      and effective method for myocardial protection during cardiopulmonary bypass.

PMID- 11837001
TI  - [Mycotic aneurysms of the thoraco-abdominal part of the aorta].
AB  - Mycotoc aneurysms (MA)--a rare and extremely dangerous lesion of the aorta. CT,
      MRA and aortography were used to diagnose MA of the thoracoabdominal areas in 2
      men of 64 and 67 years of age. The clinical picture included: fever with
      shivering with the temperature 38-39 degrees C and increasing pains in the
      inferiothoracic and lumbar areas of the spine. Hemoculture was positive in 1
      patient only. The patients were operated on. Shunting of the aorta from the
      inferiothoracic to infrarenal segments was performed in one patient with the
      exclusion of the involved portion and resection of MA. Metalloosteosynthesis of
      the spine due to destruction of LI-LII and compression of the spine were
      performed in the second patient followed by analogous shunting of the aorta and
      visceral arteries with the resection of the aneurysm. To prevent infection of the
      prostheses the shunts were wrapped up with a piece of the greater omentum. One
      patient died two months later from recurrent sepsis. The other one is alive,
      within 28 months the shunts are patent, there are no signs of a reinfection.

PMID- 11837002
TI  - [Significance of ultrasound examination and computed tomography in the diagnosis
      of pancreatic cancer].
AB  - The diagnostic sensitivity of USI for localization of a tumor of the pancreatic
      head was 89.3%, specificity--69.7%, exactness--84.4%. When the tumor was
      localized in the body-tail these indices were 85.7%, 73.4% and 78.7%
      respectively. The sensitivity of CT in cases when the localization of the tumor
      was in the head of the pancreas was 84.9%, specificity--72.2%, exactness--76.5%.
      When the tumors were localized in the body-tail these indices were 89.5%, 75.4%
      and 80.9% respectively. An associated analysis of information of the ultrasound
      and CT concerning the structure of the pancreas made the exactness of the
      diagnosis of malignization as high as 87.6%, specificity as high as 81.3%,
      sensitivity as high as 93.7%. The informative value of USI and CT depended on the
      tumor size, the presence of an inflammatory reaction of the pancreas, the
      character of a complication, if any, or of their combinations, localization and
      size of the pathological focus. In the investigation no alterations in the
      pancreas characteristic only of cancer were found. Thus, a comparison of
      diagnostic potentials of USI and CT has shown that one method does not exclude,
      but only supplements the other. CT gives more reliable results in the assessment
      of the process spread to the surrounding tissues and regional lymph nodes,
      especially when the tumor is localized in the area of the pancreas tail. USI
      helps to make more exact assessment of the involvement in the process of the
      common bile duct, pancreatic duct, and of the visceral vessels by the Doppler
      examination.

PMID- 11837004
TI  - [The first independent department of military surgery].

PMID- 11837003
TI  - [Specific features of pancreatoduodenal resection in cancer of the head and
      unciform process of the pancreas].
AB  - Pancreato-duodenal resections (PDR) were made in 134 patients with cancer of the
      pancreas, in 31 (23.1%) of them the tumor was localized in the unciform process
      of the pancreas. In 7 patients the destructive pancreatitis which complicated
      cancer PDR was completed by the external drainage of the pancreatic duct.
      Combined PDR were fulfilled in 14 (10.4%) patients including 9 (29.0%) of 31
      patients who had cancer of the unciform process. In 48 (35.8%) patients PDR was
      followed by complications. The most frequent of them were acute pancreatitis of
      the stump (32.1%) and incompetent pancreatoenteroanastomosis (18.7%).
      Postoperative lethality after PDR was 6.7%. During the recent six years no lethal
      outcomes have been observed after 45 PDR. Cancer of the uniform process of the
      pancreas is the least favorable localization. Combined PDR are followed by a
      great number of intraoperative, postoperative complications and high lethality
      rate. If the patients had mechanical jaundice, the use of double step PDR gave
      better results. If there were intraoperative signs of acute pancreatitis it was
      necessary to drain the pancreatic duct outside. The using of intraoperative
      occlusions of the pancreatic ducts is hardly justified because of a high risk of
      the development of acute pancreatitis.

PMID- 11837005
TI  - [Current problems of treatment of mine explosion wounds].
AB  - On the basis of their many-years experiences in the clinic of field surgery with
      wounded having mine explosion pathology during the Afghan war and military
      operations in the North Caucasus the authors discuss the specificity of
      terminology, diagnosis and surgical treatment of mine-explosion wounds and
      traumas. The article presents statistical data concerned with the results of
      treatment of patients with mine-explosion wounds and explosion traumas in the
      North Caucasus (1994-1996), where the mine-explosion pathology made up 15% in the
      structure of military surgical traumas, frequency of complications was 70%, total
      lethality--5.2%.

PMID- 11837006
TI  - [Wounds and traumas of the abdomen: present-day diagnosis and new approaches to
      treatment].

PMID- 11837007
TI  - [Acute insufficiency of the gastrointestinal tract in patients with severe
      gunshot injury].
AB  - Acute insufficiency of the gastrointestinal tract (GIT) in patients with severe
      gunshot injuries is an important link of pathogenesis of the polyorganic
      insufficiency syndrome. The character of the wound, the numerical score objective
      assessment of the injury severity and severity of the patient's state are
      considered to be criteria of early diagnosis of a risk of the development of
      acute insufficiency of GIT. The specific feature of "general" intensive therapy
      of acute insufficiency of GIT in severe gunshot traumas is the necessary
      application of regional anesthesia, sympatholytics, anticholinesterase agents and
      H2-blockers. Intensive "enteral" therapy of acute insufficiency of GIT in severe
      gunshot wounds includes the measures resulting in improvement of
      microcirculation, tissue respiration in organs of GIT, decompression of the
      stomach, local defense of mucosa, detoxication and early enteral balanced
      nutrition. The described method of treatment of wounded to the stomach used at
      specialized medical institutions resulted in 6.2 less lethality among this
      category of patients.

PMID- 11837008
TI  - [Stanislav Iosifovich Banaitis].

PMID- 11837009
TI  - [Role of fiber bronchoscopy in diagnosis and treatment of severe mechanical
      trauma].
AB  - The article elucidates specific features of bronchopulmonary pathology diagnosed
      by bronchofibroscopy in 218 patients with severe mechanical traumas. The
      indications to primary and repeated bronchofibroscopies are formulated. The
      significance of emergency and urgent bronchofibroscopy for early diagnosis of
      different bronchopulmonary consequencies of the trauma is shown. A description is
      given of endoscopic signs of contusion of the lung, aspiration syndrome, injuries
      of the tracheobronchial tree, different degrees of tracheobronchites, causes of
      lung atelectasis. The bronchofibroscopy is shown to be effective in prophylactics
      and treatment of bronchopulmonary pathology. The endobronchial administration of
      antibiotics, glucocorticoid hormones, mucolytic and proteolytic agents were shown
      to be effective as well as the performance of programmed bronchofibroscopy in
      prophylactics and treatment of bronchopulmonary complications. A classification
      of bronchofibroscopy in patients with severe mechanical traumas is proposed.

PMID- 11837010
TI  - Medical prescription of heroin--a review.
AB  - There are many problems associated with injection drug use, problems that affect
      both the users themselves as well as those close to them and the society in which
      they live. Whether through complications associated with drug use (multiple
      infections, mental health problems, etc) or through the consequences on those
      close to them and on society (family dysfunction, crime, etc), the costs of
      illegal drug use are considerably greater than the costs of treating drug users.

PMID- 11837011
TI  - The HIV/AIDS pandemic and its gender implications.
AB  - From 13-18 November 2000, the United Nations Division for the Advancement of
      Women, the World Health Organization, and UNAIDS convened an international
      meeting of experts in Windhoek, Namibia, to discuss the linkages between
      HIV/AIDS, gender, human rights, and human security.

PMID- 11837012
TI  - Motion to strike claim dismissed in HIV defamation suit.
AB  - On 23 April 2001, the Ontario Superior Court of Justice issued the first Canadian
      ruling on the issue of whether words inputing that a person is HIV-positive or
      has AIDS can be the basis of a defamation action per se, in the case of Serdar v
      Metroland Printing, Publishing and Distributing Ltd.

PMID- 11837013
TI  - Couple found guilty in AIDS scare.

PMID- 11837014
TI  - Ontario Court of Justice dismisses police negligence case: HIV infection a
      factor.
AB  - On 22 February 2001, the case of Chartier v Greaves was dismissed by the Ontario
      Superior Court of Justice.

PMID- 11837015
TI  - Woman wins claim for tax deductability of complementary/alternative medical
      expenses.
AB  - On 30 April 2001, the Tax Court of Canada granted judgment in favour of a
      Victoria woman who claimed that she should be entitled to deduct from her taxable
      income, as legitimate "medical expenses," her expenses for vitamin supplements
      and for rehabilitative therapies such as massage and therapeutic touch.

PMID- 11837016
TI  - Federal Court denies asylum, rejects claim that lack of adequate medical care is
      persecution.

PMID- 11837017
TI  - Criminal law and HIV/AIDS: update V.
AB  - This regular column reviews new developments in the area of criminal prosecutions
      for HIV transmission or exposure, or developments that have come to our attention
      since the last issue. Canadian developments are the focus. Cases and legislation
      from other jurisdictions are only included if they represent a significant
      development in this area of the law or for the jurisdiction in question.

PMID- 11837018
TI  - HIV/AIDS and human rights revisited.
AB  - In their article, Sofia Gruskin and Daniel Tarantola demonstrate how, as the
      number of people living with HIV and with AIDS continues to grow in nations with
      different economies, social structures, and legal systems, HIV/AIDS-related human
      rights issues are not only becoming more apparent, but also increasingly diverse.
      In the 1980s, the relationship of HIV/AIDS to human rights was only understood as
      it involved people with HIV or AIDS and the discrimination to which they were
      subjected. The concerns included mandatory HIV testing; restrictions on
      international travel; barriers to employment and housing, access to education,
      medical care, or health insurance; and the many issues raised by named reporting,
      partner notification, and confidentiality. Almost 20 years into the epidemic,
      these issues remain serious and most often have not been resolved. In the 1990s,
      however, there was increased understanding of the importance of human rights as a
      factor in determining people's vulnerability to HIV infection and their
      consequent risk of acquiring HIV infection and their chances of accessing
      appropriate care and support. And most recently, human rights have also come to
      be understood to be directly relevant to every element of the risk/vulnerability
      paradigm. Gruskin and Tarantola identify three situations and three levels of
      governmental obligations that should be considered when identifying the specific
      needs and related rights of individuals in the context of HIV/AIDS. They conclude
      that policymakers, program managers, and service providers must become more
      comfortable using human rights norms and standards to guide and limit government
      action in all matters affecting the response to HIV/AIDS; and that those involved
      in HIV/AIDS advocacy must become more familiar with the practicalities of using
      international human rights law when they strive to hold governments accountable.

PMID- 11837019
TI  - Measuring legal implementation of the international guidelines on HIV/AIDS and
      human rights.
AB  - With over 36 million people now living with the virus and over 21 million people
      dying of AIDS in the last two decades, HIV/AIDS is a global health and security
      problem. These shocking figures eclipse the human toll of many wars, and reveal
      in themselves that human rights are not being respected, protected, or fulfilled,
      either through negligent omissions or violations. A human rights approach to the
      epidemic was advocated early by advocates such as Jonathan Mann, who recognized
      that infections thrived in conditions of inequality. This approach was
      crystallized in the International Guidelines on HIV/AIDS and Human Rights that
      were developed at the Second International Consultation in 1996 convened by
      UNAIDS and the Office of the High Commissioner for Human Rights. The Guidelines
      cover three main areas: improving governmental responses in terms of
      multisectoral responsibility and accountability; widespread law reform and legal
      support services; and supporting increased private sector and community
      participation in effective responses to the epidemic. This article focuses on the
      half of the twelve Guidelines that concern rights that are justiciable and
      amenable to law reform. It highlights the responsibilities of States Parties to
      human rights treaties, as they bear the principal burden of the obligations to
      implement.

PMID- 11837020
TI  - An observer representing Canadian non-governmental organizations on Canada's
      delegation to the United Nations General Assembly Special Session on HIV/AIDS.

PMID- 11837021
TI  - Ontario to develop a viatical industry.
AB  - On 4 October 2000, Bill 119 (or the Red Tape Reduction Act, 2000) was introduced
      and received first reading in Ontario's provincial legislature. Like many of the
      other similarly titled bills the Harris government has introduced, Bill 119
      proposes to change a long list of existing statutes in an effort to make Ontario
      more business friendly. Schedule G of Bill 119 sets out a mechanism whereby a
      viatical industry in Ontario would be made legal if a licensing scheme is first
      put in place by the Ministry of Finance.

PMID- 11837022
TI  - Alberta law confining child prostitutes upheld.
AB  - The Alberta Court of Queen's Bench has determined that the Alberta Protection of
      Children Involved in Prostitution Act is not in violation of the Constitution.
      This decision overturns the ruling of the Provincial Court, which held that the
      Act infringes the rights articulated in sections 7, 8, and 9 of the Charter.

PMID- 11837023
TI  - Court dismisses constitutional challenge to ban on assisted suicide.
AB  - On 6 February 2001, the Ontario Superior Court of Justice dismissed a
      constitutional challenge by Jim Wakeford, a Toronto man with HIV/AIDS and an
      advocate for access to medical marijuana, to the sections of the Criminal Code
      that outlaw assisted suicide in Canada.

PMID- 11837024
TI  - New developments at the University of Ottawa Community Legal Clinic.
AB  - This is another in our series of articles about Canadian legal clinics that
      provide specialized services to people with HIV/AIDS. Vanessa Gruben describes
      new trends in legal issues observed by the University of Ottawa Community Legal
      Clinic since the last article by the Clinic in 1999, as well as other programs
      and projects undertaken by the Clinic over the last year.

PMID- 11837025
TI  - Political commitment, governance, and HIV/AIDS.

PMID- 11837026
TI  - HIV: getting action from our political leadership.
AB  - In this commentary on David Patterson's article on "Political Commitment,
      Governance, and HIV/AIDS," Justice Michael Kirby of the High Court of Australia
      reflects on how HIV/AIDS mobilized him and others in positions of power. He
      concludes that we are engaged not in a war, but in a great civil struggle, and
      that we have a moral duty to do what we can in this struggle.

PMID- 11837028
TI  - Supreme Court finds red cross negligent in screening blood donors.
AB  - On 19 April 2001, the Supreme Court of Canada released its first judgments in
      litigation alleging the Canadian Red Cross Society was negligent for inadequately
      screening blood donors in the early 1980s. It upheld an order that damages in the
      amount of over $2.5 million be paid to three individuals who contracted HIV
      between 1983 and 1985 from contaminated blood.

PMID- 11837027
TI  - International trade and Canadian patent law.

PMID- 11837029
TI  - Canadian court upholds Glaxo's patent on AZT.
AB  - In October 2000, the Federal Court of Appeal issued the latest ruling in the
      ongoing dispute over the validity of Glaxo's Canadian patent for AZT, upholding
      Glaxo's patent but narrowing the scope of the claims it could validly make. The
      decision is now on appeal to the Supreme Court of Canada.

PMID- 11837030
TI  - Generic drug maker wins right to sue for anti-competitive practices.
AB  - In December 2000, the Ontario Court of Appeal upheld the right of generic drug
      manufacturer Apotex Inc to sue three name-brand pharmaceutical companies for
      allegedly anti-competitive practices. Apotex's claim had been struck out by a
      lower court, but the appellate court overturned this judgment and allowed the
      suit to proceed. The facts alleged by Apotex, if eventually proved true, could
      support a court finding that the name-brand companies were in fact liable.

PMID- 11837031
TI  - Canadian court dismisses Pfizer attempt to prevent approval of generic
      fluconazole.
AB  - On 10 January 2001, Pfizer lost its bid before the Federal Court of Appeal to
      prohibit the federal Minister of Health from issuing approvals for two generic
      versions of the drug fluconazole.

PMID- 11837032
TI  - Court dismisses Eli Lilly's case against generic drug makers.

PMID- 11837033
TI  - BioChem Pharma wins patent dispute over 3TC.
AB  - In December 2000, the US Board of Patent Appeals and Interferences, a branch of
      the US Patent and Trademark Office (USPTO), upheld BioChem Pharma's claim to hold
      the patent on 3TC.

PMID- 11837034
TI  - Inquest into the death of a prisoner co-infected with HIV and hepatitis C: how
      many more will there be?
AB  - Michael Joseph LeBlanc probably became infected with HIV and Hepatitis C while
      incarcerated in a federal penitentiary. On 18 November 1999, he died at the
      Regional Hospital in Kingston Penitentiary of complications relating to hepatitis
      C. Mr LeBlanc died inhumanely, in extreme physical, psychological and emotional
      distress. His death raises the issues of transmission and prevention of HIV and
      hepatitis C, compassionate release, and health care and palliative care in
      federal prisons. An Inquest under the Coroners Act was held in Kingston, Ontario
      from 30 January to 1 February 2001. These same issues had been raised previously
      at the October 1997 coroners inquest into the death of William Bell, a person
      living with AIDS who died while incarcerated in another federal penitentiary.

PMID- 11837035
TI  - Correctional officers and prevention of HIV transmission among prisoners.
AB  - The problem of HIV transmission in prisons in Quebec and elsewhere is
      increasingly urgent and requires the attention of federal and provincial
      authorities. Prison officers are among the key players who should be kept in mind
      when preventive measures are being developed. We reprint the executive summary of
      a study conducted in federal and provincial prisons in Quebec. The goal of the
      study was to identify the factors influencing prison officers, with respect to
      whether they would agree or refuse to make accessible the tools needed for the
      prevention of HIV transmission among inmates (i.e., condoms, bleach, tattooing
      equipment, and needles). Among the factors studied are officers' perceptions and
      beliefs as well as their attitudes, perceived social norms, emotions, and
      perceived barriers with respect to making preventive tools accessible.

PMID- 11837036
TI  - Irish prison guards call for expansion of methadone access.
AB  - In many Western countries, including Canada, seroprevalence rates in prisons have
      reached epidemic levels, with infection rates among prisoners many times higher
      than among people outside prisons.

PMID- 11837037
TI  - Pharmaceutical companies abandon case against South Africa: victory for people
      with HIV/AIDS.
AB  - On 19 April 2001, 39 pharmaceutical companies bowed to worldwide condemnation and
      pressure, and completely abandoned their court action against the South African
      government over legislation that could be used to make essential drugs affordable
      for millions of South Africans.

PMID- 11837038
TI  - Nigeria--Judge denies woman with HIV access to courtroom.
AB  - In February 2001, a judge in the Ikeja High Court in Nigeria barred an HIV
      positive woman from entering her courtroom out of concern for transmission of the
      virus.

PMID- 11837039
TI  - US: court refuses to order disclosure of HIV status to police.
AB  - In February 2001, Massachusetts' highest court ruled that a man whose blood was
      splattered on police officers during his arrest is protected under that state's
      law from having to reveal his HIV status.

PMID- 11837040
TI  - China--Chengdu passes legislation discriminating against people with HIV/AIDS.

PMID- 11837041
TI  - HIV/AIDS and legal developments in Germany.
AB  - Case law has helped to define the legal environment for people infected and
      affected by HIV/AIDS in Germany. This article describes court decisions in three
      areas that may be of interest to Canadian readers: criminal law, confidentiality,
      and the use of illegal drugs to control pain. It also describes the situation of
      refugees with HIV/AIDS.

PMID- 11837042
TI  - Tainted-blood cases: updates.

PMID- 11837043
TI  - Natural helpers: a community approach to harm reduction.
AB  - This paper, by Jennifer Taylor and Theresa Jasperson, looks at a successful harm
      reduction initiative developed by Streetworks, a needle exchange program in
      Edmonton, Alberta. The Natural Helpers initiative provides and enhances the
      skills, knowledge, resources, and support that people who use injection drugs
      need in order to take care of others in their community. The evolution of the
      project, from its inception to the present situation, is described.

PMID- 11837044
TI  - Health Canada commits to strengthening efforts with respect to injection drug use
      and HIV/AIDS.
AB  - On 31 August 2001, over 20 months after the release of the Canadian HIV/AIDS
      Legal Network's report on Injection Drug Use and HIV/AIDS: Legal and Ethical
      Issues, Health Canada responded to the report by making a commitment to both
      "strengthening and expanding efforts with respect to injection drug use."

PMID- 11837045
TI  - A review of a framework for action: a four pillar approach to drug problems in
      Vancouver.
AB  - A Framework for Action: A Four Pillar Approach to Drug Problems in Vancouver
      leaves the author of this review, Jan Skirrow, seriously conflicted. According to
      Skirrow, the Framework is a useful document and reflects well on those who
      prepared it, but skips over the hard issues by agreeing that drugs are the
      problem, and then moving on to repackaging the failed program approaches of the
      past. This, Skirrow says, is not the fault of those who participated in the
      planning exercise leading to the Framework. Rather, it results from a lack of
      courage on the part of society's policymakers.

PMID- 11837046
TI  - Medical marijuana and the law: recent developments.

PMID- 11837047
TI  - Dielectric properties of supersaturated alpha-D-glucose aqueous solutions at 2450
      MHz.
AB  - Dielectric properties of supersaturated alpha-D-glucose aqueous solutions (45-56%
      w/w) at 2.45 GHz were investigated at temperatures ranging from 25 degrees C to
      85 degrees C. Penetration depth was calculated as well. At each temperature
      tested, there exists a concentration range at which the dielectric constants or
      loss factors for supersaturated glucose solutions are independent of
      concentration. These results will be helpful in studies of the Maillard reaction
      as it occurs in a microwave field.

PMID- 11837048
TI  - An efficient, accurate and robust radiometer configuration for microwave
      temperature measurement for industrial and medical applications.
AB  - The theoretical and practical design of a type of microwave radiometer
      particularly suited to industrial and medical temperature measurement is
      described. The use of sequential switching of source and reference signals with
      synchronous demodulation of switched signal components gives an efficient and
      robust instrument configuration. The radiometer measures the true, matched
      impedance effective temperature of the coupled source. Changes in noise-figure,
      gain or frequency response of the radiometer microwave amplification do not
      affect the temperature measurement. Practical microwave radiometers using this
      configuration can be simply calibrated, and have inherently stable calibration
      and excellent accuracy.

PMID- 11837049
TI  - A novel microwave applicator for tailoring the energy input for hydrothermal
      synthesis of zeolites.
AB  - A new applicator system for microwave heating of aqueous solutions for the
      hydrothermal synthesis of zeolite crystals has been developed and experimentally
      characterized. It is based on a short-ended coaxial waveguide with the solution
      being inserted as a lossy dielectric. The electrical and thermal design of the
      autoclave has been optimized by numerical simulations of the E-field and of the
      temperature distribution respectively. Different reference temperature profiles-
      a homogeneous and a gradient one--could be established within the zeolite
      solution and were held constant over time. From temperature measurements at
      various positions in the solution the two reference profiles could be verified.
      Temperature differences of less than 15 degrees C have been measured within the
      homogeneous autoclave whereas differences up to 55 degrees C have been found in
      the gradient autoclave. In the first synthesis experiments using this applicator
      zeolite crystals of the zeolite A and VPI-5-type could be successfully
      crystallized.

PMID- 11837050
TI  - Microwaves as an energy source for producing beta-SiC.
AB  - This work describes the production of silicon carbide using microwaves as the
      energy source, which was supplied by means of variable power, up to 2000 Watts,
      magnetron operating at 2.45 GHz. The obtained samples were analyzed by means of X
      ray diffraction and observed with electron microscopy (SEM). Temperatures
      achieved were around 2000 degrees C, which is the upper limit for the beta-SiC
      growth regime, before getting other SiC polytypes. Analysis of different portions
      of the sample showed that beta-SiC was the only formed compound, although free
      SiO2 and graphite were also present. Observations made by SEM demonstrated
      different crystal growth regime, meaning that thermal conditions were not totally
      uniform. The amount of beta-SiC found and the relative simplicity of the device
      prove that production of this material from silica and graphite is possible by
      applying microwaves as an energy source.

PMID- 11837051
TI  - Use of dielectric properties to detect whey protein denaturation.
AB  - Denaturation of whey proteins can be detected by the dielectric properties. The
      dielectric properties of 20% whey protein with 0, 5 or 15% sugar, 2% salt, at pH
      4 and isolated whey proteins were measured from room temperature to 100 degrees C
      at 300-2450 MHz. The temperature at which a decrease in the dielectric loss
      factor, or increase in the dielectric constant, occurred was compared to the
      temperature of denaturation as determined by DSC and found to match. The change
      in the dielectric properties is likely caused by binding of water and/or ions
      that occurs during protein denaturation. For most of the samples, the dielectric
      loss factor showed the protein denaturation, but when ions were present due to
      salt or low pH, the dielectric constant showed the denaturation.

PMID- 11837052
TI  - Electromagnetic treatment of New Zealand flower thrips (Thrips obscuratus,
      Thysanoptera:Thripidae) in deionized water.
AB  - To evaluate the impact of an electromagnetic field on thrips, New Zealand flower
      thrips, Thrips obscuratus (Crawford), were contained in a pipette that was
      suspended in an acrylic cylinder containing deionized water. Electrodes, set 85
      mm apart at each end of the cylinder, were in contact with the water. Voltages of
      between 10 and 100 kV d.c., as impulses or in steady state, were applied to the
      electrodes. Voltages of 10 and 15 kV applied in steady state did not kill all of
      the thrips. Only 2% of thrips remained alive when a voltage of 20 kV was applied
      for 10 sec. Complete mortality was achieved with 25 or 30 kV for 5 and 10 sec.
      None of the impulse trains, varying from 50 to 100 kV and 20 to 60 impulses,
      killed thrips or caused thrips to become moribund. Thrips were killed when
      exposed to 20 kV and 10 pulses when electrodes were modified and placed very
      close together.

PMID- 11837053
TI  - Infant mortality statistics from the 1999 period linked birth/infant death data
      set.
AB  - OBJECTIVES: This report presents 1999 period infant mortality statistics from the
      linked birth/infant death data set (linked file) by a variety of maternal and
      infant characteristics. METHODS: Descriptive tabulations of data are presented.
      RESULTS: In general, mortality rates were lowest for infants born to Chinese and
      Japanese mothers (2.9 and 3.4 per 1,000, respectively). Infants of Cuban, Central
      and South American, Mexican, and non-Hispanic white mothers had low rates, while
      rates were higher for infants of Puerto Rican and highest for non-Hispanic black
      mothers (13.9). Filipino mothers also had low rates. Rates were high for infants
      of Hawaiian and American Indian mothers. Infant mortality rates were higher for
      those infants whose mothers had no prenatal care, were teenagers, had 9-11 years
      of education, were unmarried, or smoked during pregnancy. Infant mortality was
      also higher for male infants, multiple births, and infants born preterm or at low
      birthweight. The three leading causes of infant death--Congenital malformations,
      low birthweight, and Sudden infant death syndrome (SIDS)--taken together
      accounted for 45 percent all infant deaths in the United States in 1999. Cause
      specific mortality rates varied considerably by race and Hispanic origin. For
      infants of black mothers, the infant mortality rate for low birthweight was four
      times that for white mothers. For infants of American Indian mothers, the SIDS
      rate was 2.4 times that for non-Hispanic white mothers. SIDS rates for infants of
      Hispanic and Asian or Pacific Islander mothers, were 40-50 percent lower than
      those for non-Hispanic white mothers.

PMID- 11837054
TI  - Job performance failure and occupational carpal tunnel claims.
AB  - Using a sample of one job type from one firm (to hold job tasks and sick
      leave/disability policy constant), we estimate the effect of demographic
      variables, job performance warnings, and workers' compensation benefits on the
      propensity to file a carpal tunnel syndrome (CTS) loss work-time claim. We find
      that disciplinary notices increase the employees' propensity to file a CTS claim.
      State maximum workers' compensation benefits are also positively related to CTS
      claim frequency, however, the relationship is not statistically significant. CTS
      claimants respond differently than other sprain/strain claimants to benefits and
      to gender. In particularly, women have relatively more CTS claims, while men have
      relatively more other sprain/strain claims in our sample. The estimates here
      underscore the importance of psychosocial factors in the filing of occupational
      CTS and sprain injuries claims.

PMID- 11837055
TI  - The reduction of chronic, nonspecific low back pain through the control of early
      morning lumbar flexion: 3-year follow-up.
AB  - Three years ago, an 18-month randomized controlled trial of chronic, nonspecific
      low back pain investigated the effectiveness of instructing subjects to restrict
      bending activities in the early morning, when the fluid content in the disc is
      increased. Pain days (as recorded by daily diaries) were reduced 23% in the
      treatment group, compared to a 2% reduction in the control (sham treatment)
      group. The purpose of the current follow-up study was to determine whether the
      results of that trial were maintained during the 3 years following completion of
      the trial. A questionnaire was mailed to the 60 subjects who completed the
      original trial. Fifty subjects completed the questionnaire for a response rate of
      83%. Thirty-one subjects (62%) continued to restrict bending activities in the
      early morning, and experienced a further reduction of 10.1 pain days per month
      (51%) since the completion of the experiment. However, some of the subjects who
      did not continue to comply also improved. Several possible explanations for the
      improvement of noncompliant subjects are offered.

PMID- 11837056
TI  - Randomized controlled trial of back school with and without peer support.
AB  - The aim of this trial was to determine whether social interaction between
      patients with long-lasting nonspecific back pain reduces subjective or objective
      disability. The participants were selected from persons visiting an occupational
      health care unit because of back pain. After a clinical examination in a
      university clinic, subjects without a specific diagnosis and having no
      disabilities preventing active rehabilitation were selected for study. The
      subjects (n = 108) were randomized into treatment (n = 54) and control groups (n
      = 54). Altogether 18 study groups, 9 treatment groups and 9 groups for controls,
      were formed. Before starting the back schools altogether 15 subjects dropped out.
      Both the treatment groups (n = 47) and the controls (n = 46) attended a back
      school consisting of 10 lessons and demonstrations supervised by a
      physiotherapist. The participants in treatment groups, but not the controls, had
      physical exercise and social intercourse with other members within the group. The
      clinical examination was repeated after 6 and 12 months. Both the treatment
      groups and the controls showed improvement in perceived functional capacity
      (assessed with Oswestry disability questionnaire) and in perceived life quality
      (assessed with 15D score). At the 6-month follow-up life quality had improved
      statistically significantly more among the participants in treatment groups than
      among the controls, and at the 12-month follow-up the Oswestry index showed
      corresponding improvement. Among subjects suffering from nonspecific back pain,
      social support improves the results of active rehabilitation.

PMID- 11837057
TI  - Returning coronary heart disease patients to work: a modified perspective.
AB  - A very large number of Americans die from Coronary heart disease (CHD); a large
      number survive. It is the goal of cardiac rehabilitation to restore the physical
      and economic status of individuals suffering from CHD. This paper reviews current
      CHD statistics, summarizes the factors that are known to cause CHD, traces the
      evolution of cardiac rehabilitation programs, and, finally, provides a new
      perspective for rehabilitating CHD patients based on job simulation.

PMID- 11837058
TI  - The Minnesota Health Partnership and Coordinated Health Care and Disability
      Prevention: the implementation of an integrated benefits and medical care model.
AB  - In the spring of 1996, the Minnesota Health Partnership (MHP) received a
      demonstration grant from the Robert Wood Johnson Foundation Workers Compensation
      Health Initiative to pilot a model of health care that was designed to combine
      the best practices of general health and workers' compensation medical care. This
      paper outlines the genesis of the MHP, and the relationship of its Coordinated
      Health Care and Disability Prevention model to traditional managed care and 24-h
      care models. In order to effectively implement disability prevention principles
      within a primary care clinical setting, it is essential to increase health care
      provider awareness that the disability relating to a specific impairment can be
      positively impacted by specific clinical strategies. The basis and specifics of
      these strategies are also discussed. Plans for the evaluation of this model will
      also be described.

PMID- 11837059
TI  - Perspectives. Chronic care means altered practice, new institutions.

PMID- 11837060
TI  - ["Prosthetic condition" and satisfaction with dentures].
AB  - This study introduces the concept of 'prosthetic condition', combining the
      professionally assessed complete denture quality and quality of the residual
      alveolar ridge. In a group of 397 complete maxillary and mandibular denture
      wearers the prosthetic condition was assessed and the denture satisfaction
      recorded. The total prosthetic condition (maxillary and mandibular combined) was
      good in 225 (57%), moderate in 81 (20%), and poor in 91 (23%) subjects; the
      mandibular prosthetic condition was good in 155 (39%), moderate in 148 (38%), and
      poor in 94 (23%) subjects; 297 (75%) subjects were satisfied with their dentures.
      None of the criteria used for the prosthetic condition could explain the denture
      satisfaction. Furthermore, there was no significant correlation between
      prosthetic condition and denture satisfaction.

PMID- 11837062
TI  - [Caries and heredity].
AB  - Although host genes play a certain role, the development of carious lesions is
      determined predominantly by local influences in the oral cavity, especially by
      microbial plaque and dietary carbohydrates as substrate for acidogenic bacteria.
      How strong or weak the influence of the hereditary component on caries really is,
      has been the subject of discussions for the last decades. The geneticist
      Professor Sofear is optimistic about prospects to decrease the caries risk by
      manipulation of genes. However, more detailed analysis of known facts shows that
      the majority of genetic differences is caused by indirectly operating mechanisms.
      Furthermore, these genetic factors can be overruled by local protective and
      compensating influences.

PMID- 11837061
TI  - [Dental implants: cost-effectiveness analysis].
AB  - The efficacy and effectiveness of dental implants have been proven during the
      last years. An economic evaluation must be integrated within the clinical
      evaluations to determine economic (allocative) efficiency. According to the
      literature dental implants will show better results. The treatment is, however,
      more expensive. Assessment of costs and benefits can lead to more efficiency in
      dental care. The possibilities to evaluate the outcome of treatment are discussed
      and essential aspects of the economic evaluation are described.

PMID- 11837063
TI  - [Can lichen planus exist on the gingiva?].

PMID- 11837064
TI  - [Contact allergy in and around the mouth].
AB  - Contact allergic reactions in and around the mouth are not frequent, but they can
      have very unpleasant consequences. Discussed are the most important materials
      that can cause reactions in patients and dental personnel. Particulary the
      enormous increase in the use of latex gloves has caused a rise in latex allergy
      and contact dermatitis by rubber additives. Acrylates are also important contact
      sensitizers; they can cause the dentist serious trouble.

PMID- 11837065
TI  - [Latex hypersensitivity, an increasing problem].
AB  - As a result of the frequent use of rubber containing products in medical health
      care, latex allergy is becoming an increasing problem. Based on a case history of
      a hospital employee, this paper will discuss the cause and consequences of this
      specific allergy.

PMID- 11837066
TI  - [Eugenol in root canal cement:possible cause for urticarial reactions].
AB  - A case is reported of a patient with chronic urticaria. The correlation between
      the symptoms and dental treatment gave rise to the supposition that a root canal
      cement was causing the trouble. This hypothesis has been tested with epicutaneous
      patch tests and intradermal tests in cooperation with the Utrecht University
      Hospital (the Netherlands), Institute of Dermatology, Clinical Allergy Section. A
      causal relationship with eugenol, a cement constituent, could only be established
      through provocative oral ingestion. Nevertheless, caution is needed when dealing
      with chronic urticaria in view of the risk of anaphylactic reaction.
      Consequently, the article highlights the allergenic aspects of eugenol, as a
      substance associated with balsam of Peru. Attention is focused on the fact that
      eugenol, used in dental materials, is able to elicit and maintain urticaria
      protractedly.

PMID- 11837067
TI  - [Complete rehabilitation of the secondary cleft lip and palate patient].
AB  - This article presents the results of total reconstruction of the 'end stage of
      cleft lip and palate deformity' in fourteen patients. The deformity consisted of
      varying degrees of 1. midface retrusion and/or mandibular protrusion; 2
      malocclusion; 3. nasal deformity; 4. lip deformity; 5. palate or alveolar
      fistulas and 6. nasal speech. These deformities resulted in aesthetic and
      functional problems. By a comprehensive approach in one session--total
      reconstruction--functional and aesthetic improvement was achieved in all
      patients.

PMID- 11837068
TI  - [Corticosteroids in dental practice].
AB  - In this article some pharmacologic aspects of corticosteroids and their main
      medical indications are reviewed. In addition, the use of corticosteroids in
      dentistry and their interference with dental treatment are discussed.

PMID- 11837070
TI  - [Decision making in the dentist-patient relationship].

PMID- 11837069
TI  - [Dental research in the Netherlands: an international orientation].
AB  - Analysis of dental scientific literature (section Dentistry & Odontology of the
      Science Citation Index) has revealed that the majority of the contributions to
      dental science come from the USA, the UK and Japan. Also Dutch scientists showed
      up as active contributors, especially when viewed against the distribution of
      IADR-members and dental practitioners over the world. The scientific output in
      the Netherlands is evenly spread over the various dental subdisciplines, although
      some emphasis is seen on the fields of cariology and social dentistry.

PMID- 11837071
TI  - [Amyloidosis. Etiology and clinical manifestations].
AB  - Amyloidosis is a disorder of protein metabolism in which autologous proteins are
      deposited intercellularly as fibrils with characteristic staining properties and
      ultrastructural features. Amyloid deposits may be focal, localized to a
      particular tissue or organ, or distributed systemically. Many different chemical
      forms of amyloid have been identified and amyloid may accumulate as a result of a
      variety of different pathogenetic mechanisms. Amyloid deposits rarely regress,
      but rather tend to increase inexorably in size. Since there is no effective
      therapy for systemic forms of amyloidosis, they carry a poor prognosis in most
      cases.

PMID- 11837072
TI  - [Diffuse swelling on the bottom lip].

PMID- 11837073
TI  - [Professional autonomy and the dentist-patient relationship].
AB  - This article discusses the concept of professional autonomy from an ethical
      viewpoint. First it is explained how the professional autonomy of the dentist
      relates to the autonomy of the patient. Subsequently the influence of the health
      care system is discussed.

PMID- 11837074
TI  - [Blood crusts on the bottom lip].

PMID- 11837075
TI  - [Dental implants: one or two stages?].
AB  - Dental implants can be inserted in one or two stages. The promoters of the two
      stages implant systems believe that submersion is essential for osseointegration.
      Animal and human studies, however, have shown that implants can also be
      successful when the one stage procedure is used. In this article the principles
      and the (dis)advantages of both procedures are discussed.

PMID- 11837076
TI  - [Tertiary crowding in the lower front teeth. Two observations].
AB  - Tertiary crowding, especially in the lower dentition, is shortly discussed. Two
      cases are illustrated that show the uncertainty regarding the often stated
      influence of the third molars in this respect.

PMID- 11837078
TI  - [Discipline advice medicine 1994. University (main)programs].

PMID- 11837077
TI  - [Is segmental osteotomy of the jaws outdated?].
AB  - In earlier days segmental osteotomies had a broad field of indications. In the
      era of combined surgical-orthodontic treatments, they are pushed far into the
      background. This article shows that this development is unjust. If carefully
      indicated, segmental osteotomies still have a well-defined place in our armory of
      surgical interventions. With their elegance and the compulsion to respect detail
      they are not only of marked didactic value, but they also fill a gap, especially
      in the treatment options for the lower jaw. Far from being obsolete, they should
      still belong to the routine options when orthognathic surgery is considered.

PMID- 11837079
TI  - [Eat well and stay healthy. Changing perspectives on good nutrition].
AB  - Nutrition as a discipline evolved out of medical and bio-chemical thinking on the
      relation between food and health. Until the 1950s nutrient deficiencies dominated
      the nutritional way of thinking. From this moment attention was directed to
      nutritional consequences of the welfare state. During the last years a gradual
      shift in emphasis has taken place from cardiovascular diseases to nutrition and
      cancer, and to nutrition of the elderly. New is the attention on novel and
      functional foods as a means to promote nutritional health, besides the ongoing
      efforts to change food habits.

PMID- 11837080
TI  - [Healthy eating in 1995].
AB  - The report 'Dietary Guidelines' of the Dutch Nutrition Council advises about the
      composition of a balanced diet, conductive to good health. Such a diet supplies
      all nutrients in the right amounts and has a preventive function towards those
      diseases of the affluent society which are nutrition related. The key principle
      of a healthy diet is 'variety'. Present day food habits make the recommendation
      'moderation with (saturated) fat' a compelling second one. A logical follow-up
      when reducing the amount of fat in the diet is the recommendation of a generous
      amount of bread, potatoes, vegetables and fruit, in order to compensate fat
      reduction. For many consumers this means an increase in the consumption of these
      products.

PMID- 11837081
TI  - [Nutrition education in dentistry].
AB  - Reduction of the number of sugar containing snacks is the most important
      nutritional measure to prevent dental caries. Frequent use of acid food and
      drinks can lead to erosion of the enamel. Snacks containing as little fat and as
      much complex carbohydrates and rough materials as possible are preferred. In
      nutrition education, general principles of health education, such as attention
      for personal and social circumstances, have to be kept in mind. Prolonged use of
      the nursing bottle containing sugar-rich drinks must be prevented. Attention is
      needed for young people who frequently use soft drinks, sportsmen and women,
      people with a special dietary pattern, 'grazing' people and people with an
      illness or handicap.

PMID- 11837082
TI  - [Relationship between nutrition and dental caries in a scientific perspective].
AB  - The consumption of sugars is supposed to be one of the main etiological factors
      of dental caries. However, in epidemiological studies only a faint relationship
      is found between nutrition and caries. One reason is the preventive effect of
      fluoride in modern industrialized countries. In this article attention is paid to
      factors which can modify the harmful effect of sugars in foods and allied
      products: the composition and consistency of the product, the way the product is
      consumed, environmental factors in the mouth such as composition of saliva and
      plaque, and local availability of fluoride. Results are presented of an
      epidemiological study into the relationship between consumption of sweet snacks
      and caries experience of primary school children.

PMID- 11837083
TI  - [The importance of mineral supplementation for dentition and jaw].
AB  - In this article the importance of mineral suppletion for teeth and jawbone is
      explained in a step-wise manner. The steps discussed are the pre-eruptive phase
      of teeth and the growth, adult and ageing phase of the skeleton. Mineral
      suppletion should be seen as a measure to prevent dental caries (fluoride) and to
      ensure a maximal resistance against the spontaneous bone loss during ageing.
      Therefore, it seems not suitable for therapy of osteoporosis. If an enhanced bone
      loss occurs as a result of decreased production of sex hormones or immobility,
      mineral suppletion will probably have a minor effect. An optimal mineral intake
      will ensure a maximal peak bone mass built up during the growth phase of bone, a
      maintenance of this peak bone mass as much as possible during the phase of
      neutral bone balance and a minimal bone loss during the ageing period with
      negative bone balance.

PMID- 11837084
TI  - [Feeling like a snack. The influence of taste on our eating habits].
AB  - This article describes the physiological, social and emotional aspects of food.
      Human physiology determines 'the need' for food, society 'the possibilities' and
      our emotions 'the choice'. Grazing is becoming a common phenomenon in modern
      society: the frequent eating of snacks between meals, or even instead of meals.
      One of the consequences is an increasing dental risk, due to repeated acid
      attacks on the enamel. For a better understanding of these changing eating habits
      and the emotional values of food, the Dutch centre for the research of taste
      (CSO) has developed the so-called 'Taste-Cube'. This cube attaches human values
      to different types of food. The value of a product is created by the consumer,
      according to his 'internal logic'. In this article these concepts are explained.

PMID- 11837085
TI  - [Between biting and swallowing. Physiology of mastication].
AB  - Masticatory movements in man are almost cyclic and mainly vertical. The precise
      movements depend on many factors, such as the amount of food, its consistency and
      the morphology of the occlusal planes. In normal function chewing forces range
      from 10 to 50 N. For solid food the chewing performance can be characterized by
      determining the particle size of the comminuted food. Chewing movements and
      chewing forces result from a coordinated pattern of muscle activities. The basic
      pattern results from a central pattern generator in the brain stem. The control
      of the precise timing and intensity of the muscle activity necessary for
      commuting the food is a result of anticipation and of sensoric information from
      the masticatory system. During chewing the tongue plays an important role in
      transporting the food.

PMID- 11837086
TI  - [Role of saliva during mastication].
AB  - The chewing process is necessary to facilitate the digestion of food. For this
      process not only the grinding of the food by mechanical forces is of importance,
      but also the penetration of the food with saliva. This last process results in
      the formation of a smooth foodbolus that can be easily swallowed. In addition,
      the intimate contact between the fine ground food particles and the salivary
      digestive enzymes is a prerequisite for a rapid digestion. A high quality of
      saliva is an essential factor to protect the dental elements against attrition
      and, on the other hand, to promote the digestion process.

PMID- 11837087
TI  - [Dental erosion and nutrition].
AB  - Dental erosion is the chemical dissolution of tooth tissue by the attack of acids
      stemming from either the stomach or the diet. The organic acids produced by
      plaque bacteria are inducing dental caries. Risk factors for dental erosions are
      the frequent use of acidic foodstuffs (e.g. citrus fruits) and acidic drinks
      (e.g. cola's, fruit juices and sport drinks). As a risk factor from saliva has
      been detected: a low salivary secretory rate combined with a low pH and low
      buffer capacity. Prevention from dental erosion can be attained by 1. reducing
      the number of acidic moments during the day, 2. shortening the contact time and
      intensity in the oral cavity, 3. neutralizing a diet acid by drinking non-acidic
      milk (products), 4. regular fluoride application with a neutral gel and 5. pH
      raising tablets e.g. bicarbonate- or urea-containing chewing gums, when the
      occlusal area is not eroded.

PMID- 11837088
TI  - [Chewing with shortened dental arches].
AB  - Masticatory performance as measured with (objective) chewing tests is correlated
      with the number of teeth (the food platform area). In general, however, the
      masticatory ability (the subjective chewing experience) is sufficient as long as
      20 or more 'well-distributed' teeth remain, such as is the case with an SDA, when
      the anterior teeth and the premolar teeth are present. Research indicates that an
      SDA does not lead to altered food selection. Studies have shown that a free-end
      removable partial denture generally does not improve the oral function in terms
      of masticatory ability or chewing comfort, unless in case of extreme shortened
      dental arches with only the anterior teeth present.

PMID- 11837089
TI  - [Masticatory performance with mandibular implant-retained overdentures].
AB  - It was investigated in a clinical trial whether the masticatory performance of
      complete-denture wearers depended on the support for their mandibular dentures by
      implants or mucosa. The trial involved the provision of a new maxillary denture
      and either a new conventional mandibular denture (mucosa-borne), a mandibular
      overdenture retained by two IMZ-implants (implant-mucosa-borne), or a mandibular
      overdenture on a transmandibular implant (TMI; mainly implant-borne). In
      comparison with mandibular implant-retained overdentures, subjects with
      conventional dentures needed 1.5 to 3.6 times more chewing strokes for an
      equivalent reduction in particle size. No differences in masticatory performance
      were found between subjects with IMZ-implants and those with TMI. This suggests
      that the increased stability of the mandibular denture with implants determines
      the wearer's masticatory performance, rather than the support by implants.

PMID- 11837090
TI  - [Dentures and food selection. A survey in elderly women].
AB  - Having complete dentures can have a negative influence on dietary intake and
      dietary composition, which can lead to an unhealthy situation, particularly for
      the elderly. In order to get more information on this subject, 86 women between
      54 and 74 years old, who were treated at an university clinic, completed
      questionnaires about their chewing of and preference for various foodstuffs. From
      the results of this study the dietary intake of dietary fibres, protein and iron
      appeared to be lower in women with complete dentures. After correction for the
      total intake of energy these differences disappeared. The former group also
      indicated that they had more difficulties chewing bread, tough and soft meat, raw
      vegetables, apples and snacks. No differences were found concerning preference.

PMID- 11837091
TI  - [General medical information. Vitamin supplementation: too much of a good thing
      is bad].

PMID- 11837092
TI  - [Orthodontic possibilities for young patients with missing maxillary incisors].
AB  - In the orthodontic treatment of young patients with missing maxillary incisors
      one should make an effort to avoid prosthetic solutions. This not only applies to
      situations with agenesis of maxillary lateral permanent incisors, but also to
      those cases in which maxillary incisors cannot be maintained after trauma.
      Standard solutions are presented for various sagittal jaw relationships and types
      and number of teeth missing. Specific rules have to be observed for the closure
      of spaces due to missing teeth in order to reduce the occurrence of papillae
      retraction and to place the substituting teeth in such a position that their
      crowns can be built up to look like the originals. This requires mesiodistal
      angulations that deviate from the standard ones, a proper distribution of crown
      width and in most cases a permanent retention with a palatally bonded thin
      multistranded wire.

PMID- 11837093
TI  - [Osseointegrated implants in adolescents. A three year study].
AB  - In 15 adolescents (age 13.2 to 19.4 years) in the late dental stage implants (n =
      27) were chosen to replace missing teeth due to congenital absence or trauma. The
      patients were followed for at least 3 years. No fixture losses occurred. Only
      minor loss of bone support at the fixture was observed, while adjacent tooth
      surfaces showed some loss. Infra-occlusion of the implant restorations was
      noticed in patients with residual craniofacial growth. Thus, the dental and
      skeletal maturation, and not the chronological age, must be taken into account to
      avoid infra-occlusion. Furthermore it is important to gain enough space for the
      fixture in the mesio-distal direction in order to avoid the risk of marginal bone
      loss at teeth adjacent to the implants.

PMID- 11837094
TI  - [Prosthetic possibilities in the treatment of missing anterior teeth in
      adolescents].
AB  - Prior to the judgement on the best solution in the treatment of missing teeth in
      adolescents, an inventory of all problems has to be made. On the basis of this
      inventory the dentist can search for solutions by means of an analysis of
      castings and a wax-up. The combination of these solutions is indicative for the
      therapy which has to follow. In case tooth material has to be added, a prosthetic
      solution will be necessary. The condition of the teeth adjacent to the open space
      is the major factor in the considerations on which prosthetic solution is best.
      To be able to treat in a predictable way, a wax-up is necessary.

PMID- 11837095
TI  - [Front tooth replacement and the possible application of implants in young
      patients].
AB  - Oral implantology is a new treatment alternative and is often considered for
      treating the loss of teeth in patients of all ages. However, care has to be taken
      when using implants in younger patients, as implants in the growing patient can
      have considerable disadvantages. In this article indications, contra-indications
      and risks are discussed and an overview of conventional treatment alternatives is
      given. Finally, guidelines for the use of implants in children and adolescents
      are formulated.

PMID- 11837096
TI  - [Dental caries diagnosis and judgement of dental caries risk. A review of
      preventive strategies and treatment].

PMID- 11837097
TI  - [Calculation and responsibility over 35 years of dentistry. Farewell lecture of
      Professor Dr. G. Boering].

PMID- 11837098
TI  - [Esthetic dentistry?].

PMID- 11837099
TI  - [General medical information. Viral hepatitis].

PMID- 11837100
TI  - [Ectodermal dysplasia: a heterogenic deviation].
AB  - The 'problem' of ectodermal dysplasia is discussed in conjunction with a case
      report and a review of the literature. In a range of hereditary disorders all
      ectodermal structures can be effected in a variable way: reduction of the amount
      of hair, sweat glands and sebaceous glands, and a complete or partial anodontia
      of the deciduous and permanent dentition with malformation of the erupted teeth.

PMID- 11837101
TI  - [Prescription of antibiotics for the prevention of bacterial endocarditis by
      dentists in the Netherlands].
AB  - In 1993 a representative sample of dental practitioners in the Netherlands was
      questioned on the use of antibiotics for the prevention of endocarditis in the
      previous year. Most of the responding dentists (67%) reported prescription of
      antibiotics for patients at risk. Some of them prescribed an antibiotic regimen
      that differed from the guidelines drawn up by the Dutch Heart Foundation. In 1992
      only 47% of the responding dentists prescribed antibiotics for the prevention of
      endocarditis entirely according to these guidelines.

PMID- 11837102
TI  - [Skin and mucosal grafts. Their place within preprosthetic surgery and
      implantology].
AB  - In preprosthetic surgery, both skin grafts and oral mucosal grafts can serve as a
      dressing for mucosal defects. Grafts from the palatal mucosa are better suited
      for reconstruction than skin grafts or oral mucosal grafts with another origin,
      because palatal grafts lack many of the disadvantages of all other types of
      grafts. The limitation of palatal mucosa to be used as grafting material is its
      availability. However, cultured palatal mucosa may offer a solution when large
      defects have to be covered.

PMID- 11837103
TI  - [Towards a system of quality care in dentistry in the Netherlands].
AB  - Monitoring and improving the quality of rendered health care in a systematic way
      has been laid down in Dutch legislation. In Dutch family health care
      particularly, many initiatives have already been taken to improve the quality of
      health care utilizing a pre-defined systematic approach. In recent years various
      groups in The Netherlands took initiatives to maintain and improve quality of
      care in dentistry. This publication reports on some of the frequently used
      constructs and the state of the art in The Netherlands. A proposition for the
      development of a system of quality monitoring and improvement is presented. It is
      furthermore suggested that all parties involved should collaborate to achieve the
      joint goal.

PMID- 11837104
TI  - [NTG Spring Congress 1995 'The BIG impact'].

PMID- 11837105
TI  - [A reabsorbed third molar: what to do?].

PMID- 11837106
TI  - [General medical information].

PMID- 11837107
TI  - [Denture adhesives can be useful].
AB  - The use of denture adhesives has been discouraged by the dental profession. The
      negative attitude toward denture adhesives originates from scientific reports
      about the irreversible damage of denture bearing tissues caused by the
      application of denture pads and do-it-yourself liners. This survey of literature
      shows that, so far, no harmful effects have been reported about powder, cream or
      liquid denture adhesives. Therefore, it is justifiable to prescribe denture
      adhesives in some patients in order to improve their denture comfort. Dentists
      should be proactive in giving patients appropriate information about the
      different kinds of denture adhesives and in demonstrating their proper use.

PMID- 11837108
TI  - [Cooperation in wearing orthodontic appliances].
AB  - In orthodontics the degree of treatment outcome largely depends on patient
      cooperation. In this article factors related to cooperation with removable
      appliance wear are discussed.

PMID- 11837109
TI  - [Intraoral radiographs of dental implants in the edentulous mandible].
AB  - Radiographs of dental implants in the edentulous mandible, which are suitable for
      evaluation studies, are difficult to obtain. This article describes the
      development of an aiming device for intraoral radiography of the crestal bone
      around the neck of dental implants. Error analysis of serial radiographs
      indicated only small deviations in reproducibility. Subsequently three methods of
      measurements of marginal bone level around the neck of dental implants are
      described, measurements with: 1. a computerized image analysis system, 2. a
      magnifying glass, and 3. a digital sliding gauge. The intra- and interobserver
      error analysis showed that determining the precise bone height on the image is
      responsible for a large standard deviation for each method. Measurements with a
      digital sliding gauge are preferable, since this method is easy to put into
      practice, whereas the accuracy matches the accuracy of the two other methods.

PMID- 11837110
TI  - [Alcoholism and dentistry].
AB  - In this article the physical and psychological consequences of alcohol abuse are
      considered. In addition the interaction between alcohol abuse and oral health and
      dentistry is discussed.

PMID- 11837111
TI  - [Tetanus prophylaxis in injuries. Guidelines for the dental practice].
AB  - The severe and often fatal infection of tetanus is very rare in the Netherlands
      because of the mild Dutch climate and adequate vaccination programme.
      Nevertheless, in case of wounds, either extra- or intra-orally, tetanus
      prophylaxis should be considered. The immunity of the individual patient can be
      estimated by his vaccination record. Dentists see a large number of patients with
      dental trauma and/or facial wounds. Depending on the immune status of the
      individual patient, tetanus prophylaxis might be necessary. Especially at risk
      are patients with inadequate or deficient vaccination, e.g. those who spent their
      childhood abroad and patients who had their last immunisation over ten years ago.
      Vaccination in case of wounds should follow a strict protocol to prevent an
      inadequate tetanus prophylaxis.

PMID- 11837112
TI  - [Cyst-like lesion in the lower jaw].

PMID- 11837113
TI  - [New cases of tuberculosis].

PMID- 11837114
TI  - [Prescription of antibiotics for periodontitis patients by dental practitioners
      in the Netherlands].
AB  - In 1993 a representative sample of dentists in the Netherlands was questioned on
      the use of antibiotics in the treatment of periodontitis. It was found dat 50% of
      the general practitioners had a positive attitude, 15% a negative one and 35% had
      an indifferent attitude towards the use of antibiotics in periodontal treatment.
      Almost 40% of them indicated the prescription of antibiotics for periodontal
      reasons in the previous year. Most of the dentists (71%) prescribed a combination
      of metronidazole and amoxicillin. The average prescription frequency in 1992 was
      18 times. The prescription frequency and the choice of a combination of
      metronidazole and a broad spectrum penicillin in the treatment of periodontitis
      is discussed, emphasizing the importance of the traditional mechanical therapy,
      the disturbance of the colonization resistance by means of antibiotics and the
      worldwide concern about the usage of antibiotics.

PMID- 11837115
TI  - [Aspirin, a risk factor for bleeding at dental procedures].
AB  - Aspirin is widely used as an antithrombotic drug in the prevention of
      cardiovascular events. It causes a usually mild bleeding tendency. When used
      before dental or surgical procedures, aspirin increases the risk of bleeding,
      contrary to the postoperative administration of aspirin, which has not been
      associated with increased risk of bleeding. To estimate the risk of bleeding, a
      history on bleeding tendency and information on the recent use of aspirin is
      worthwhile. It is recommended to delay procedures for at least one week after the
      last ingestion of aspirin, if possible. In case of urgent surgical procedures or
      in patients who suffer from serious bleeding due to the use of aspirin, a single
      preoperative transfusion of a suspension of platelets is usually sufficient to
      antagonize the effects of aspirin. Tranexamic acid can be given alternatively.
      The preferred policy depends on the type of the procedure to be performed, or the
      nature of the bleeding.

PMID- 11837116
TI  - [Dental health in drug and alcohol addicts].
AB  - The aim of this study was to describe the dental health status of a group of
      Dutch twenty- to forty-year-old drug addicts (n = 121) and to compare the results
      on DMFS with data of an in age comparable sample of the general non-addicted
      adult population in the Netherlands (n = 1532). The average DMFT of the addicted
      group was 16.9. The average DMFS of this group differed statistically
      significantly from the DMFS of the general non-addicted population of the same
      age (52.1 versus 38.9). Statistically significant differences in DMFS were also
      found between the various age groups. In the youngest three age groups the
      percentage of addicted subjects with cervical plaque on one or more teeth was
      76.5%, 82.4% and 88.2%. Bleeding of the gingiva occurred in almost all addicted
      subjects. Only 36% of the addicts had visited their dentist less than a year ago
      and 18% of them brushed their teeth less than once a day. It is concluded that a
      large gap exists in dental health status and behaviour between drug addicts and
      the general non-addicted population. Dental care as an integral part of the care
      for drug addicts is advocated.

PMID- 11837118
TI  - [NVT Spring Congress "Glass"].

PMID- 11837117
TI  - [Publishing in the native tongue?].
AB  - This study investigates the motives of Dutch dental researchers to publish their
      scientific data either in international journals, written in English, or in Dutch
      dental journals. Questionnaires were sent and 115 of them were completed and
      returned (response 57.5%). 108 of the respondents strongly preferred publishing
      in international dental journals. This option is connected with the researchers'
      own interests and the perceived importance for their field of study. 42% of the
      respondents consider publishing in Dutch newspapers more profitable than writing
      articles for Dutch dental journals. The Journal of Dental Research is considered
      the journal with the highest recognition.

PMID- 11837119
TI  - [Antrum perforation: yes or no?].

PMID- 11837120
TI  - [Helicobacter pylori].

PMID- 11837121
TI  - [Diagnosis and treatment of halitosis].
AB  - Halitosis or foetor ex ore is a frequent and complex problem with a
      multifactorial etiology. Nevertheless, in the majority of cases local oral
      conditions are the causes of the bad breath and therefore an extensive oral
      examination is the first step towards the identification of the source of
      malodor. A correct diagnosis will depend on analysis of data gathered from the
      patient's halitosis history, oral examination and additional laboratory and
      diagnostic tests.

PMID- 11837123
TI  - [Hepatitis B vaccine: simple and effective].
AB  - All workers in the dental office are at risk for hepatitis B infection. Hepatitis
      B has a chronic course in 10% of cases and may lead to liver cirrhosis, liver
      cancer and death. According to European law, approved in April 1994, employees
      have to be protected against biological agents in their working environment. The
      employer has to offer vaccination, free of costs, in case of risk for infection
      with hepatitis B. The vaccination scheme consists of three doses. Vaccination is
      successful if the antibody-titer (anti-HBs) is higher than 100 IU/L. Excellent
      immune memory is then formed, giving protection for more than 10 years. Testing
      of anti-HBs or revaccination is not necessary during that period of time. Up to
      three additional vaccinations should be given if the anti-HBs titer remains below
      100 IU/L; if the anti-HBs remains lower than 10 IU/L, there is no protection
      against hepatitis B. Someone with a titer between 10 and 100 IU/L is protected
      (if the titer was measured twice), but it is still unknown how long protection
      will last. Revaccination is recommended if the titer falls below 10 IU/L at any
      time. The policy after a needle-stick accident with HBsAg positive material is
      determined by the question whether a person has ever had an adequate reaction to
      hepatitis B vaccination (i.e. anti-HBs > 100 IU/L). If this is the case, no
      action is needed. If not, passive-active vaccination has to be given, by
      hepatitis B immunoglobulin (HBIg) and hepatitis B vaccination.

PMID- 11837124
TI  - [Osteoporosis and jaw bone reduction].
AB  - The relationship between osteoporosis and residual ridge reduction has been
      investigated in many studies. As a result it can be concluded that it is not easy
      to measure the extent of osteoporosis of the jaws. Several studies have shown
      that individuals with general signs of osteoporosis do not necessary have an
      osteoporotic mandible or maxilla. The same applies to the relationship between
      osteoporosis and residual ridge reduction in edentulous patients and osteoporosis
      and bone loss in patients with periodontal diseases. Taken into account the
      positive effect of healthy food intake and functional loading in the prevention
      and treatment of osteoporosis, it can be expected that they also influence the
      bone quality of the jaws. Preservation of strategic teeth or roots under the
      overdenture as well as the insertion of implants have a positive effect on the
      bone of the jaws.

PMID- 11837125
TI  - [Healthy diet].
AB  - A proper diet is important with regard to oral health and even more so with
      regard to general health aspects, such as coronary heart disease and various
      types of cancer. Present guidelines on diet in the Netherlands emphasize the
      importance of variety in diet, limited use of (saturated) fats, ample use of
      complex carbohydrates and limited use of cholesterol as well as alcohol.

PMID- 11837126
TI  - [X-ray after apex resection is sometimes difficult to judge].

PMID- 11837127
TI  - [Implant-retained overdentures. Part 1. Clinical findings from an evaluation
      study].
AB  - A total of 429 patients who had received implant overdenture treatment, were
      clinically investigated by two dentists. Implant survival was high, especially
      for implants placed in the mandible. Results for the maxilla appeared far less
      promising. Complications that were observed predominantly concerned inflammation
      of the peri-implant tissues and poor oral hygiene. No statistically significant
      correlation could be found between patient and treatment characteristics at
      baseline and the clinical treatment outcome.

PMID- 11837128
TI  - [Diplopia following local anesthesia].
AB  - In dentistry diplopia following injection of a local anaesthetic is a rare
      complication. A case is presented in which a patient developed a transient
      paralysis of a lateral rectus muscle. The literature concerning orbital
      involvement of local anaesthetics is discussed. The most likely explanation for
      the occurrence of these adverse effects is intra-vascular injection in the
      superior or inferior alveolar artery with backflow into the vessels supplying the
      orbit.

PMID- 11837129
TI  - [Oral care in irradiated patients].
AB  - A group of 152 dentate patients who had been irradiated in the head and neck
      area, has been studied for several aspects of oral care. One third of them (34%)
      was referred for the first oral screening after radiotherapy had started. In
      spite of intensive oral and dental care during and after radiotherapy, several
      complications occurred. More valid methods are necessary to evaluate oral care in
      patients who are subject to head and neck radiotherapy.

PMID- 11837130
TI  - [The law concerning medical treatment agreement. Opinions of dentists].
AB  - The aim of this pilot study was to investigate the view of Dutch dentists on
      certain elements of consent to dental treatment. A total of 120, randomly
      selected general practitioners, drawn from the Dutch Dental Association registers
      and from four different regions, were invited to participate; 34 took part in
      group discussions. The form of these discussions was semi-structured. Questions
      were based on a literature survey and two interviews with experts. The outcome of
      the discussions indicate that most general practitioners are ill-informed about
      informed consent and, furthermore, that their understanding of the process is
      rather poor.

PMID- 11837131
TI  - [The educational continuum and the specialization in oral diseases and jaw
      surgery].
AB  - Throughout the world can be seen a strong development towards the requirement of
      both a dental and a medical degree for oral and maxillofacial surgeons. Such
      requirements call for a critical review of the various parts of the curriculum
      and the optimum educational continuity in the sequence dentistry--medicine--oral
      and maxillofacial surgery.

PMID- 11837132
TI  - [Quantify quality].

PMID- 11837133
TI  - [Please remove M3's to accommodate eruption of M2's].

PMID- 11837134
TI  - Trauma: many disorders, but one path to recovery.

PMID- 11837135
TI  - Addiction treatment's haves and have-nots: what's wrong with this picture?

PMID- 11837136
TI  - Will SAMHSA finally fulfill its promise?

PMID- 11837137
TI  - Don't blame managed care for system inefficiencies.

PMID- 11837138
TI  - Making technology solutions affordable.

PMID- 11837139
TI  - Tapping the potential of isomer science.

PMID- 11837140
TI  - Prescribing patterns. Building new tools for effective prescribing.

PMID- 11837141
TI  - Is drug advertising informing the consumer?

PMID- 11837143
TI  - Pegram's regress: a missed chance for sensible judicial review of managed care
      decisions.

PMID- 11837142
TI  - An eHealth diptych: the impact of privacy regulation on medical error and
      malpractice litigation.

PMID- 11837144
TI  - An economic model to analyze the impact of False Claims Act cases on access to
      healthcare for the elderly, disabled, rural and inner-city poor.

PMID- 11837145
TI  - The WTO dispute settlement understanding: an unlikely weapon in the fight against
      AIDS.

PMID- 11837146
TI  - Vicarious liability for anesthesiologists.

PMID- 11837147
TI  - The National Commission on Nurse Anesthesia Education 10 years later--Part 2:
      Years following the commission (1994 to present).
AB  - In 1989, the National Commission on Nurse Anesthesia Education was implemented to
      reverse a severe shortage of CRNAs. The Commission, charged with scrutinizing all
      aspects of nurse anesthesia educational programs, developed 8 goals with
      corresponding strategies that were used by the Commission Implementation Task
      Force to actualize its charge. These goals and strategies contributed to an
      increase of annual graduates from nurse anesthesia programs and the development
      of 10 new programs. These activities were documented in Part 1 of this article,
      which appeared in the October 2001 AANA Journal. Following completion of the 3
      year project, the Council on Accreditation of Nurse Anesthesia Educational
      Programs (COA) and the AANA Education Committee began carrying out the final
      recommendations made by the Commission. Part 2 addresses the accomplishments of
      the Education Committee and COA in implementing the recommendations of the
      Commission, discusses current status of educational programs and CRNA manpower,
      and identifies roles for both educators and practitioners in protecting the
      future of the profession.

PMID- 11837148
TI  - Preinduction activities: a closed malpractice claims perspective.
AB  - The American Association of Nurse Anesthetists Foundation conducts an ongoing
      study of closed malpractice claims that involve nurse anesthetists. A team of 8
      CRNA researchers has to date investigated 223 closed claim files from the St Paul
      Fire and Marine Insurance Company. Research findings have demonstrated that
      failure to provide appropriate anesthesia care relative to the Scope and
      Standards for Nurse Anesthesia Practice was significantly associated with adverse
      anesthetic outcomes. Claims that involved inadequate preinduction activities (n =
      22) were analyzed in the context of their compliance with published standards of
      care. The largest group of claims in this analysis (59%) involved damaging
      respiratory events, 28% entailed damaging cardiovascular events, and the
      principal issue in 13% of these claims involved failure to seek available
      information such as laboratory studies on the medical record. The most prevalent
      occurrence with damaging respiratory events was undocumented airway assessment in
      27% of the claims. In 55% of these claims, the medical history was not completely
      documented. The surgical procedure categories were general surgical (32%),
      obstetrical (27%), otolaryngogical (23%), orthopedic (14%), and gynecologic (5%).
      The involved standards of care are reviewed, and recommendations are made
      regarding consistent completion of preinduction activities.

PMID- 11837150
TI  - The Connell airway: a feasibility study.
AB  - Management of the patient's airway during sedation preferably includes not only a
      dependable passageway for gas exchange, but also a reliable way to deliver oxygen
      and measure expired carbon dioxide. The Connell airway is a newly described
      modification of the nasopharyngeal airway that provides a conduit for gas
      exchange and 2 additional channels: 1 for the administration of oxygen and the
      second for monitoring of expired gases. We studied 10 sedated patients who had a
      Connell airway placed orally to support their airway during their procedure.
      Although minor difficulties were noted with early use of the device, subsequent
      experience demonstrated good performance of the device for airway support and
      oxygen delivery, easy observation of the end-tidal carbon dioxide waveform, and
      few minor complications. We believe that the Connell airway is a feasible airway
      design that could have use in the management of a patient's airway during
      sedation and that it warrants further investigation.

PMID- 11837149
TI  - The analgesic effects of subhypnotic doses of propofol in human volunteers with
      experimentally induced tourniquet pain.
AB  - This double-blind, placebo-controlled study was performed to determine whether
      subhypnotic doses of propofol have analgesic or sedative effects. Of 48 subjects
      randomly assigned to 1 of 4 bolus-infusion treatment groups, group 1 (n = 16)
      received propofol at 16 micrograms/kg per minute; group 2 (n = 16) received
      propofol at 32 micrograms/kg per minute; and group 3 (n = 8) received 10%
      intralipids at 16 micrograms/kg per minute; and group 4 (n = 8) received 20%
      intralipids at 32 micrograms/kg per minute. Following a bolus of the study drug,
      a maintenance infusion was started and continued throughout the study. Thirty
      minutes after the study drug began infusing, an Observer's Assessment of
      Alertness/Sedation Scale was completed, a tourniquet was inflated, and a maximum
      tourniquet tolerance time (TTT) was obtained. Pain was assessed every 5 minutes
      while the tourniquet was inflated and immediately before deflation using a 0 to
      10 verbally administered numeric rating scale (NRS). No significant differences
      in TTT were noted between the 2 propofol groups. However, the TTT for both
      propofol groups differed significantly from the control group (intralipid groups
      combined) (P < .05). There was a statistically significant difference in the time
      it took the propofol groups to reach a NRS score of 8 or greater when compared
      with the control group (P < .05). Sedation scores differed significantly between
      the control and the propofol at 32 micrograms/kg per minute groups (P < .05). The
      results of this study suggest that propofol given at subhypnotic doses could
      serve as a valuable adjunct for acute postoperative pain management.

PMID- 11837151
TI  - The BIS monitor: a review and technology assessment.
AB  - In the administration of anesthesia, clinicians have traditionally relied on a
      variety of autonomic signs to assess the pharmacologic effects of anesthetic
      agents on the central nervous system. As any experienced clinician knows, these
      signs can be misleading and lead to overdosing or underdosing of anesthetic
      drugs. The development of a monitor to measure the bispectral index (BIS)
      provides anesthetists with the first clinically tested and US Food and Drug
      Administration-approved monitor to assess the effects of anesthesia on the
      cerebral cortex. This article reviews the development of the BIS monitor,
      compares the BIS monitor with other commonly used clinical monitors, assesses the
      cost-benefit from the use of this monitor, and explores some of the possible uses
      for this monitor outside of the operating suite.

PMID- 11837152
TI  - Thermoregulation: anesthetic and perioperative concerns.
AB  - Hypothermia has long been common in anesthesia and has largely been seen as an
      inconvenience. For many years, it was viewed as inevitable. But hypothermia is
      much more than an inconvenience, and it is no longer inevitable. Hypothermia is
      closely associated with significant morbidity both intraoperatively and
      postoperatively. Hypothermia may begin in the preoperative holding area, so
      efforts to prevent it should begin there as well. Effective intraoperative and
      postoperative warming methods are known and commonly available, but they remain
      underused. Understanding how and why core temperature declines in association
      with anesthesia and surgery and safe, effective methods to prevent that decline
      will enable nurse anesthetists and perioperative nurses to increase both the
      comfort and safety of their patients while reducing costs to the institution.

PMID- 11837153
TI  - [Mineral bezoar of the stomach and small intestine].

PMID- 11837154
TI  - [Current concepts in classification of lymphoid tissue tumors].
AB  - An analysis of the data of foreign literature and of the author's personal
      experiences allows a conclusion to be made concerning the evolution of views on
      lymphoid tissue tumors. The author proposes a classification of lymphomas, the
      algorithm of diagnosis of the lymphomas, describes certain clinical
      characteristics of different types of lymphomas.

PMID- 11837155
TI  - [Multiple organ failure or multiple organ incompetence as a manifestation of a
      system reaction of the body (apropos of the article by I. A. Eriukhin "Multiple
      organ failure syndrome. Essence of understanding and correction". Vestn. khir.,
      2000, no. 4, p. 12-19)].

PMID- 11837156
TI  - [Destructive pancreatitis. Strategy and tactics of treating at the current stage
      (impressions of a participant in the IX Conference of Surgeons, 20-22 September,
      2000)].

PMID- 11837157
TI  - [Current approaches to surgical treatment of intrapulmonary metastases].

PMID- 11837158
TI  - [Some aspects of developing reflux esophagitis in patients with hiatal hernias].
AB  - An examination of 60 patients with gastro-esophageal reflux has shown that a
      continuous contact of the gastric mucosa with the gastric contents and retarded
      evacuation from the stomach are considered to be the principal factors in the
      development of reflux-esophagitis.

PMID- 11837159
TI  - [Surgical treatment of duodenal ulcers].
AB  - Selective proximal vagotomy (SPV) was fulfilled in 440 patients with ulcer of the
      duodenum, 30.0% of them being operated upon for relative indications, and 70.0%
      for different complications of the ulcer. Different draining operations were made
      in 219 patients with stenosis. Draining operations were made in 10.6% of 254
      patients without stenosis of the pylorus who had big and deep penetrating ulcers
      which could disturb duodenal passage on their healing. Resections of the stomach
      after Billroth-I were fulfilled in 20 of 43 patients with combined gastric and
      duodenal ulcers, and after Hofmeister-Finsterer in 23 patients in view of a
      danger of malignization. The best results were obtained after proper SPV and
      after operations eliminating stenosis and saving the evacuating mechanism of the
      pylorus (transversal duodeno-duodenostomy in 10 patients and duodenoplasty--in
      22). Resection of the stomach should be performed by the Billroth-I method.

PMID- 11837160
TI  - [Functional results of an operation for forming an "artificial stomach" after
      gastrectomy and subtotal distal resection of the stomach].
AB  - The operations of plastic substitution of the resected stomach with a transplant
      of the jejunum were fulfilled in 81 patients. The aim of the operations was to
      establish the natural passage through the duodenum. Of 55 able-bodied patients 31
      returned to their regular work, 14 patients changed their work to easier. An
      investigation of the main parameters of metabolism and of the questionnaires
      distributed among the patients have shown a high level of the "quality of life"
      of the patients operated upon at later terms after operations. The involvement of
      the duodenum in digestion due to the jejunal plasty of the resected stomach made
      the disorders of digestion rarer, improved the quality of life of the patients at
      later terms after operation, thus promoting their social and labor
      rehabilitation.

PMID- 11837161
TI  - [Some regularities of morphological changes in liver tissue exposed to
      electricity].
AB  - An experimental investigation of the character and spread of morphological and
      histological alterations in the liver was performed in order to follow their
      dependence on the regimen of using an electrosurgical apparatus for resection and
      coagulation of the liver tissue.

PMID- 11837162
TI  - [Clinico-experimental basis for regional and systemic administration of
      thiopoietins in liver cirrhosis. Report I].
AB  - The authors present results of studying the effectiveness of a new class of
      medicines--preparations of the group "Glutoxim" (Molixan, Redoxell, Bikvolit,
      Liglutin) obtained on the model of experimental cirrhosis of the liver in 76
      white rats caused by dimethylnitrosamin, and describe their first experience with
      using thiopoietins in 24 patients with cirrhosis of the liver in a surgical
      clinic. It was found that three weeks of treatment with Molixan and Bikvolit gave
      a significant hepatoprotecting effect (less amount of the connective tissue,
      reduction of the dystrophic processes in hepatocytes). A positive effect of
      Redoxell was shown in longer time of treatment. When used in clinic therapy with
      thiopoietins was followed by correction of the T-cell link of immunity in most
      patients. One of the most important results of treatment with medicines of the
      group of thiopoietins was a substantial improvement of the quality of life of the
      patients.

PMID- 11837163
TI  - [On technique of surgical treatment of extravasal stenosis of the celiac plexus].
AB  - Under analysis were the results of intraoperative observations during surgical
      treatment of 243 patients with extravasal stenosis of the celiac trunk. Special
      attention was given to anatomical correlation of the celiac trunk, celiac plexus,
      median arcuate ligament and median crura of the diaphragm involved in the
      compression of the celiac trunk. For the development and substantiation of
      optimal methods of decompression of the celiac trunk 106 anatomical preparations
      were investigated. The variants of the anterior diaphragm arteries and of the
      celiac trunk vessels were revealed whose injuries can result in intraoperative
      bleedings. Different variants of the operative technique depending on the
      anatomical conditions are proposed.

PMID- 11837164
TI  - [Debatable and unsolved questions of surgical tactics in perforation of the
      colon].
AB  - An analysis of operative treatment of 86 patients from 24 to 85 years of age with
      perforation of the colon of different genesis was made. The differential approach
      to decision on the surgical strategy allows the author to make a conclusion that
      a radical operation such as resection of the injured segment of the colon with
      the colostomy has the best immediate result independent of the cause of the
      perforation. Palliative operations of suturing the perforation and colostomy or
      bringing the injured parts of the colon onto the abdominal wall are followed by
      frequent pyo-septic complications and high rate of lethality.

PMID- 11837165
TI  - [Bacteriological features of peritonitis in perforative gastroduodenal ulcer].
AB  - Bacteriological investigation of 137 probes of the exudate from the abdominal
      cavity has revealed positive results in 60.6%. The detection of microbial flora
      was the more frequent the greater was the spread and degree of peritonitis. The
      monoculture was revealed in 92.8%, the colibacillus being the most frequent. The
      isolated microbial flora was sensitive to antibiotics of the cephalosporin group.

PMID- 11837166
TI  - [Omentoplasty in limb surgery].
AB  - The authors describe a method of omentoplasty used in 55 patients with
      lymphodema, chronic osteomyelitis, scalped bad burn wounds. Good results of
      treatment were noted in all the patients.

PMID- 11837167
TI  - [Changes in the kallikrein-kinin system and lipid peroxidation in patients with
      diffuse peritonitis, complicated by adult respiratory distress syndrome].
AB  - The authors present results of their investigation of the state of kallikrein
      kinin system (KKS) and lipid peroxidation (LP) in blood of 22 patients operated
      upon for acute diffuse peritonitis as a complication of different surgical
      diseases. In 8 patients who later died the respiratory distress-syndrome of
      adults (RDSA) developed at the early postoperative period. Activation of KKS and
      LP were observed in all the patients both in the venous and arterial blood, but
      it was more intensive in patients with RDSA. In the same group of patients the
      level of the metabolites under study was higher in the arterial than in the
      venous blood, which suggests a disturbances of the metabolic function of the
      lung. The results of the investigation allow a conclusion that antiprotease drugs
      should be included in the complex treatment of RDSA.

PMID- 11837168
TI  - [Comparative evaluation of various methods of surgical correction in
      Hirschsprung's disease].
AB  - An analysis of results of treatment of 46 patients with Hirschsprung's disease
      has shown that complications at the postoperative period were observed in 17 of
      39 children subjected to radical operations by the methods of Duhamel, Swanson
      and others. A number of common and specific for each traditionally used method
      disadvantages responsible for the results of treatment were found out. The
      authors have developed a method of treatment of Hirschsprung's disease including
      ablation of the aganglionary zone and forming the termino-terminal colorectal
      anastomosis between the descended colon and the rectum mobilized and resected
      from the parasacral-perineal access. The new method was used in operations on 7
      patients without complications.

PMID- 11837169
TI  - [Free transplantation of skin onto the face].
AB  - Basing on their experiences the authors describe principal technical methods of
      free transplantation of skin in different areas of the face. Their personal
      observations are used as illustrations.

PMID- 11837170
TI  - [Experience in using complex flaps on microvascular anastomoses in treating with
      skin cancer on the face and scalp, appearing in scarred areas].
AB  - The authors describe 11 patients operated upon for carcinoma of the face skin and
      hairy part of the head developing from scars of various etiology. The
      substitution of vast defects which had appeared after dissection of a tumor was
      performed by means of microsurgical autotransplantation of tissue complexes. The
      following vascularized autotransplants were used: musculus serratus anterior,
      scapular and radial grafts. Positive results were obtained in all the cases. The
      authors consider the microsurgical autotransplantation of tissue complexes to be
      a necessary component of surgical treatment of carcinoma of the skin and hairy
      part of the head developed from vast and deep scars.

PMID- 11837171
TI  - [Comparative evaluation of the efficacy of pre- and intraoperative reserving of
      autoblood in surgical treatment of ischemic heart disease and while using a Cell
      Saver].
AB  - A prospective investigation included 142 patients who had undergone operations of
      coronary bypass under conditions of extracorporeal circulation for ischemic heart
      disease. Two methods of taking blood were used: one day before operation and at
      the beginning of operation. The transfusion of autoblood was performed after
      cessation of the extracorporeal circulation. Cell saver was used during
      operations on all the patients. The preoperative reserving of autoblood promoted
      the greater degree of hemodilution (both during extracorporeal circulation and at
      the early postoperative period). The intraoperative reserving of autoblood led to
      saving higher indices of content of hemoglobin, number of erythrocytes and
      hematokrit index at the early postoperative period. However, when using the cell
      saver, the method of reserving blood (7-8 ml/kg of body mass) was of no
      substantial influence on the frequency of using the allogenic blood.

PMID- 11837172
TI  - [Complications of laparascopic cholecystectomy].
AB  - 1389 laparoscopic operations were fulfilled for chronic and acute cholecystitis.
      In 41 patients (3%) it was necessary to pass on to laparotomy. Injury of
      hepaticocholedochus was made in 6 patients (0.5%), bleedings appeared in 9
      (0.7%), bile leakage at the postoperative period--in 9 (0.5%). Subhepatic abscess
      was formed in 2 patients. Wound complication sat at the postoperative period
      developed in 33 patients (2.5%), pulmonary complications--in 7 patients. One
      patients died of myocardial infarction. The most frequent causes of
      intraoperative injuries of the vascular and duct structures of the hepatoduodenal
      ligament and the bile bladder bed were found to be cicatricial and inflammatory
      alterations of the areas mentioned and non-typical variants of the anatomical
      situs of the vessels and bile ducts. The detailed examination of the patients at
      the preoperative period, knowledge of the anatomical variants of the disposition
      of bile and vascular structures in the operation zone allow to prevent their
      intraoperative injury.

PMID- 11837173
TI  - [Use of "regeneration stimulator" in surgical treatment of postoperative ventral
      hernia].
AB  - During experimental hernioplasty with the application of the "Regeneration
      stimulator" in 38 dogs it was discovered that the rehabilitation period of the
      abdominal walls after the operation was considerably shorter. An experience with
      surgical treatment of 42 patients with postoperative ventral hernias is
      described. To remove the defect of the anterior abdominal wall by different
      intraoperative methods "the regeneration stimulator" was used in the zone of
      plasty. Recurrent hernias were noted in 1 of 42 patients. The method can be
      recommended for treatment of this category of patients.

PMID- 11837174
TI  - [Fluorescent method of studying the binding sites of serum albumin for assessing
      status of patients with purulent-septic diseases].
AB  - The concentration and properties of the binding centers of the albumin molecule
      in blood serum of patients with pyo-septic diseases (peritonitis,
      pancreatonecrosis and sepsis) were investigated. The patients of this category
      were shown to have a considerably decreased and greatly variable indices of the
      general concentration of albumin and of effective concentration of albumin in
      their blood serum. The fluorescent indices were established to correlate with the
      severity of the disease, efficiency of treatment, prognosis of the development of
      the disease and its outcome.

PMID- 11837175
TI  - [Surgical treatment of synchronous bilateral lung tumors].
AB  - An experience with treatment of 29 patients with bilateral malignant tumors
      includes primary tumors and those of metastatic origin. When large bilateral lung
      resections are necessary, the consecutive operations are considered to be
      expedient with intervals of 4-6 weeks. When the operation volume is not more than
      lobectomy in one side and an atypical or segmental resection in the other side,
      it is possible to fulfill a one-step intervention from the transsternal access.
      The surgical treatment for bilateral tumors should be supplemented by radio- and
      chemotherapy. Surgical treatment for bilateral tumors of the lungs is permissible
      but in the side of the maximal lesion followed by treatment of the rest of the
      tumor by nonsurgical methods.

PMID- 11837176
TI  - [Retrograde venography and embolization in postoperative recurrence of
      varicocele].
AB  - Percutaneous retrograde venography was performed in 10 patients with recurrent
      varicocele after surgical ligation (the Ivanissevich operation) of the spermatic
      vein. Combined scleroembolization with Thrombovar plus steel coils was performed
      in 8 patients. In two other patients either sclerotherapy or embolization only
      was made depending on their anatomical peculiarities. No recurrences were seen
      during 6-60 months of follow-up in 9 patients in whom the occlusion of all venous
      feeders was technically successful. It was concluded that embolization was a
      minimally invasive and effective procedure and hence the transcatheter treatment
      should be considered a method of choice for post-surgical recurrent varicocele.

PMID- 11837177
TI  - [Multiple endocrine neoplasia type IIA syndrome (Sipple's syndrome) in one
      family].

PMID- 11837178
TI  - [Successful treatment of a spontaneous esophageal rupture, complicated by
      pyopneumothorax and pleural empyema].

PMID- 11837179
TI  - Managing subacute cutaneous lupus erythematosus.
AB  - Managing a patient with subacute cutaneous lupus erythematosus subsequent to
      ultraviolet exposure is challenging to health care professionals. A discussion of
      the disease process, a case study, and practical strategies for patient care will
      be presented.

PMID- 11837180
TI  - The sentinel node biopsy in melanoma patients.
AB  - A palpable node is the first and most frequent sign of regional metastasis of
      malignant melanoma (MM). Nevertheless, the role of the elective lymph node
      dissection in patients with cutaneous melanoma remains one of the most debated
      topics of surgical oncology. Lymphatic mapping and sentinel node (SN) biopsy are
      supported as the standard of surgical care of MM by the World Health Organization
      and the Sunbelt Melanoma Clinical Trial. The only way to identify patients
      harboring microscopic nodal metastases is the elective complete regional
      lymphadenectomy or, as preferred today for its high specificity and minimal
      morbidity, the SN biopsy, which provides a histologic representative sample of
      the entire basin.

PMID- 11837181
TI  - Calciphylaxis in the patient with chronic renal failure.
AB  - Calciphylaxis is a rare, painful, necrotizing skin condition that occurs most
      frequently in patients with chronic renal failure who are receiving dialysis.
      These patients commonly have secondary hyperparathyroidism. Treatment involves a
      multidisciplinary approach. Surgical wound debridement, local wound care, pain
      control, and nutritional support are the primary care issues that must be
      addressed. The outcome is often poor, with the fatal outcome often resulting from
      sepsis.

PMID- 11837182
TI  - Bioterrorism: a renewed public health threat.
AB  - In the aftermath of the terrorist attacks of September 11, the United States is
      coming to terms with new and urgently felt public health and safety concerns
      related to the threat of bioterrorism. The recent history and the legislative
      agenda emerging to prevent, monitor, and respond to bioterrorism in the United
      States are described.

PMID- 11837183
TI  - What's your assessment?

PMID- 11837185
TI  - Leading through the blur: leadership in difficult times.

PMID- 11837184
TI  - Tinea corporis.

PMID- 11837186
TI  - [Impact of Brownian motion and magnetic fields of erythrocytes on spin echo
      signal of blood protons].
AB  - A reduction in blood So2 and ESR is shown to lead to the decay of a spin echo
      signal. This effect is explained by the impact of red blood cell magnetic field
      fluctuations caused by the Brownian motion. The authors propose to use the effect
      to monitor red blood cell agglutination.

PMID- 11837187
TI  - [Approximate methods for calculation of the likelihood of radiation-induced
      complications. 1. ACLRC method. 2. CERC method].
AB  - The paper deals with the method of approximate calculation of the likelihood of
      radiation complication (ACLRC) in normal organs and tissues when the volume of
      information is insufficient to determine all the parameters of a mathematical
      model. How to use the approximate method of LRC in the heart is exemplified. A
      method for approximate calculation of equivalent radiation conditions (CERC) in
      the focus of a lesion is offered, which allows the preset analytical (or graphic)
      description of the relationship of resorption likelihood (RL) to SOD for the
      fixed volume of a lesion focus to be transferred to the description of this
      relationship for other volumes.

PMID- 11837188
TI  - [Specific features of QRS-complex identification algorithms for real-time ECG
      systems].
AB  - The paper reviews the existing methods for identifying QRS complexes. An attempt
      is made to make a well-defined classification of available algorithms in an
      approach to QRS detection. Emphasis is laid on the consideration of specific
      requirements for such algorithms by computer-aided real-time ECG systems. A task
      of choice of the most suitable method is formulated. An algorithm based on the
      well-known principles of frequency-time detection is proposed as an alternative
      solution of this task. The algorithm makes it possible to single out QRS
      complexes from real-time ECG and to effectively make a digital signal processing
      by available optimized libraries. The method initially used in the Matlab package
      has been integrated within the laboratory computerized ECG system.

PMID- 11837189
TI  - [Experimental testing of an isolating-clutch endoprosthesis of the hip joint: the
      first results].
AB  - The paper presents the results of experimental tests of a new endoprosthesis. The
      study is devoted to the important issue the prevention on hip joint
      endoprosthetic instability occurring due to metallosis and its tissue responses.
      The prosthesis has the new design element an artificial capsule that protects
      tissue from metallosis. Experimental data were obtained by clinical observations
      of surgery-undergone dogs aged under a year and by X-ray, morphological and
      spectral studies. That the artificial capsule is highly effective in preventing
      the instability of the prosthesis and that the function of a limb is not limited
      by the capsule are shown.

PMID- 11837190
TI  - [Chronoreactiometric system with biotechnical feedback].
AB  - The paper deals with a principle in the construction and apparatus realization of
      a biotechnical feedback system (BT-FS) for self-regulation (correction) of rapid
      motor reactions (RMR). Experiments have indicated that the system has good
      training and rehabilitative abilities as the examinee develops permanent RMR.

PMID- 11837191
TI  - [An external cardiac pacemaker for prevention of atrial fibrillation].
AB  - The paper presents an account of and the technical data of a new external
      pacemaker to be used to prevent atrial fibrillations. It shows it expedient to
      design such devices and presents their characteristics.

PMID- 11837192
TI  - [Optimization of methods and improvement of technical means in combination with
      the nonspecific reparative regeneration stimulator ximedone in dermatoplasty
      surgery].
AB  - Treatment of extensive tissue defects should be complex, whose basis is an early
      free skin plastic repair with obligatory addition of agents that enhance the
      reparative capacities of tissues. For this, the authors propose a number of
      original appliances (forceps, variants of dermoperforators, bandage, etc.) and
      drugs, such as ximedon (tablets, 5-10% aqueous solution, lanolin-vaseline-based
      ointment, talc-based powder), whose clinical trials in 300 patients have shown
      their high therapeutical effect. The time of preparation of the wound surface for
      dermatoplastic interventions became shorter and the frequency of poor outcomes of
      operations reduced.

PMID- 11837193
TI  - [Assessment of the quality of radiographic medical films and chemicals for
      photochemical treatment].
AB  - The paper outlines conditions ensuring the high quality of X-ray image on the
      film at the end production stage in relation to the quality and compatibility of
      two systems: a X-ray film proper and chemicals for its treatment. The types of X
      ray films and chemicals used in therapeutical-and-prophylactic establishments of
      the Russian Federation, their characteristics, as well as the required content of
      information printed on the consumer's package, which allows them to choose for
      adequacy for probable use.

PMID- 11837194
TI  - [Use of an apparatus for automatic lung straightening in the management of the
      pleural cavity in the postoperative period].
AB  - An apparatus for automatic lung straightening may be used in medical technologies
      employed in thoracic (lung) surgery in the postoperative rehabilitation of a
      patient. This apparatus may automatically (without a physician's or a nurse
      observance) maintain tension relief in the pleural cavity in the patient on an
      individual basis, which is required for complete lung strengthening. Its use
      greatly reduces the number of postoperative complications in the lung, such as
      residual cavities, edema, and empyema of the pleura. This apparatus is to go into
      quantity production as a cheap, expendable device to prevent AIDS and hepatitis.

PMID- 11837195
TI  - [Determination of areas of alternating magnetic field action on a patient's
      body].
AB  - The pattern of an induction field (B) is of great importance for
      physiotherapeutical treatment using an alternating magnetic field (AMF). The
      outline of the B field is determined by the shape of a device generator.
      Programmes for calculating the B induction field at any space point for the
      generator as a current ring and a square current loop are given. To know the
      spatial pattern of the B magnetic field is inadequate to determine the areas of
      biophysical AMF action. AMF induces a stress field (ES). The latter with regard
      to the human body and organs gives rise to a drop field of acting potentials
      (Ua). The latter is a measure of biophysical action at each local point of a
      patient's body. The Es field depends solely on the shape of the device generator.
      The Ua field does on this and the form of the human body and organs. Whether the
      Ua field can be found is discussed. The author proposes to develop programmes for
      calculating the Ua fields when the generator and human body are usually aligned.
      It is concluded that the shapes of the generators to act on each specific organ
      should be standardized.

PMID- 11837196
TI  - [Testing the characteristics of X-ray apparatuses by using test cassette].
AB  - An X-ray TKP-1 M test cassette has been designed for effective testing of the
      basic operational parameters of X-ray diagnostic apparatuses that most frequently
      require inspection and adjustment during their use. The use of the cassette makes
      it possible to check the values of anode voltage on the basis of the improved
      double exposure method that simultaneously exposes two comparable parts of an X
      ray film. Equivalent filtration is accomplished by a rotary shutter having sector
      slots, whose total angle is 30 degrees, which ensures 12-fold reduction in X-ray
      radiation at the site of disk rotation. A diaphragm and a step circular copper
      attenuating wedge are located in alignment with the shutter, each step ensures 12
      fold reduction in radiation of certain power (at 40, 44, 48, 52, 57 kV, etc.).
      The pattern and pulsation of anode voltage and the duration of exposure are
      assessed by the pattern of an image of the small-diameter hole in the shutter.
      The perpendicularity of a radiation beam and alignment of an indicator are
      estimated by the shape of an image of the central vertical longitudinal hole.

PMID- 11837197
TI  - [Milta-F: a magnetic infrared laser therapeutic apparatus with a photorecorder
      for diagnosis, prognostication and treatment of inflammatory diseases of the
      adnexa uteri].
AB  - Laser biophotometry is an objective method to diagnose and to predict the course
      of inflammatory diseases of the uterine appendages. By taking into account its
      simplicity, reliability, and validity of findings, a MILTA apparatus should be
      recommended in additional studies of patients.

PMID- 11837198
TI  - [AGM-03: microprocessor gastric acidity meter].
AB  - The paper outlines an AGM-03 microprocessor acidogastrometer, a diagnostic device
      for direct measurement of acidity in the upper gastrointestinal tract (GIT). The
      AGM-03 device is cheapest among new-series acidogastrometers developed by the
      State Research and Production Enterprise "ISTOK-SISTEMA". It is intended for use
      at small hospitals and polyclinics when acid-dependent GIT processes are under
      study.

PMID- 11837199
TI  - [Legionnaires disease: results of 25-years of studying infections, problems and
      perspectives of research].
AB  - The paper summarizes the results of 25-year study of Legionnaires' disease
      (Legionnaire's bacillus infection) in its epidemiology, diagnosis, and
      prevention, the taxonomy and biology of the causative organism. Emphasis is laid
      on the contribution of the Russian school of investigators in studying this
      problem. Despite the intensive efforts in investigating the infection and its
      causative organism, there are still many problems in predicting and preventing
      the epidemics of Legionnaires' disease, which annually occur in different
      countries of the world. Legionnaires' disease is a typical example of technogenic
      infections: active industrial and domestic uses of closed water circulating
      systems in industry and aerosol sources promote the spread of the infection
      caused by Legionnaire's bacillus and make its control in these systems. Despite
      the introduction of current immunological and molecular genetic methods,
      diagnosis is effective only for L. pneumophila, serogroup 1. The sensitivity and
      specificity of methods for diagnosis and identification for other 15 L.
      pneumophila serogroups and 41 species of L. bacilli are far from being perfect.
      L. bacilli are also a most popular object for studying the biochemical and
      genetic aspects of its intracellular parasitism.

PMID- 11837200
TI  - [Mobile genetic elements and their role in evolution of pathogenic bacteria].
AB  - The review discusses a role of mobile genetic elements in the evolution of
      pathogenic bacteria. Particularly great emphasis is placed on two recent
      thoroughly studied mobile genetic elements--the islets of pathogenicity and
      cassettes containing antibiotic resistant genes. The matters associated with the
      structural organization of these types of mobile elements, mechanisms of their
      translocations and involvement in the production of pathogenic bacteria are
      considered in detail. The data on the impact of macroorganisms on the horizontal
      dissemination of genetic information are discussed.

PMID- 11837201
TI  - [Strategies of adaptive changes in Vibrio cholerae in natural water reservoirs].
AB  - The currently available data on different variations in cholera vibrio habiting
      in water reservoirs are summarized. The pattern of variations of the main signs
      of vibrions is discussed in the context of "typical-atypical-inactive-resting
      (uncultivable) forms". Emphasis is placed on the reversible pattern and adaptive
      essence of variation whose basis is clonal and selective processes in the
      heterogeneous bacterial population. Possible populational mechanisms responsible
      for the development of epidemic types of cholera vibrions in the aqueous
      ecosystems as a prerequisite for human morbidity are discussed. The efficiency of
      ecological and molecular genetic studies for the epidemiology of cholera is
      recognized.

PMID- 11837203
TI  - [Ultrastructural analysis as a method of studying bacteremia in infectious
      diseases].
AB  - To study bacteremic processes with transmission electron microscopy, blood groups
      were examined in the representative groups of patients with typhoid fever,
      generalized forms of yersinosis, pseudotuberculosis, Flexner's shigelosis, and
      Sonne's shigelosis at different stages of acute cyclic diseases and in those with
      chronic Salmonella typhi carriage. Bacteremia of typical unaltered causative
      organisms is shown to occur only in the feverish period of disease. The
      morphofunctional organization of a causative agent in this period is similar to
      that of museum bacterial strains, except that the bacteria circulating in the
      blood of patients have vesicles that are morphologically equivalent to endotoxin.
      In reconvalescence, the blood circulation of causative organisms continues, but
      they appear as morphologically changed bacteria and as forms with their defective
      cellular wall (spheroplasts and protoplasts). Transmission electron microscopy
      reveals bacteria of other systematic groups in the patients' blood when acute
      Salmonella typhi carriage is under way or when there are typhoid fever-induced
      complications or relapses, clinically unfavorable running of typhoid fever,
      generalized forms of yersinosis and pseudotuberculosis are present. In chronic
      Salmonella typhi carriage, the patients' blood displays altered bacterial cells
      and forms with defective cell wall, among them there are prominent morphological
      types that are structurally identical to uncultured bacterial forms. The study of
      blood samples from infected patients has show that transmission lectron
      microscopy can be used to detect blood circulating microorganisms at different
      stages of acute and chronic patterns of an infectious process.

PMID- 11837202
TI  - [Epidemiological aspects of nonspecific prevention of infectious diseases].
AB  - Whether immunomodulators may be used not only to treat immunodeficiencies, but to
      prevent infectious diseases has been under general discussion in the past years.
      The use of immunomodulators is mostly substantiated and promising in preventing
      polyetiological infections (e.g. acute respiratory diseases) against which there
      are not available specific preventing agents (vaccines) or the latter, if
      available, are ineffective. This has been evidenced by controlled epidemiological
      tests that show the potential and actual efficiency of immunomodulators as agents
      of nonspecific prevention of infectious diseases. The basic lines of studies,
      which make it possible to elaborate the tactics of drug use, based on the
      definition of epidemic indications and on the choice of the optimal preventive
      measures, are substantiated.

PMID- 11837204
TI  - [Etiotropic therapy of the most widespread viral infections].
AB  - In the past years the recently increased interest in designing new antiviral
      agents is primarily associated with the obvious clinical effect of agents of this
      kind, which have undergone long-term trials. These included aminoadamanthanes,
      analogues of nucleosides, etc.). The review summarizes the results of searches
      for and medical application of new-generation antiviral agents intended mainly to
      prevent and treat 4 most common and dangerous groups of diseases: HIV infection,
      influenza and acute respiratory viral infections, viral hepatitis, and herpes
      related diseases.

PMID- 11837205
TI  - [Immunologic approaches in infectology].
AB  - Current immunological approaches to infectology make it possible to study the
      populations of infectious agents, their effects on various protective immune
      responses in the population of macroorganisms and to provide a more profound
      insight into the interaction of these populations in the past, at present, and,
      perhaps, in the future.

PMID- 11837206
TI  - [Study and prevention of mixed infections, transmitted by Ixodes ticks].
AB  - The paper deals with the main aspects of mixed infections transmitted by Ixodes
      ticks: the biocenotic bases of existence of natural focal mixed infections, the
      magnitude of their spread, the indices of mixed infestation and the relationships
      of different causative organisms with Ixodes ticks and reservoir hosts, the
      spatial relations of mixed parasitic systems, the incidence of tick-borne mixed
      infections, the problems of their diagnosis and clinical manifestations, as well
      as the tasks of complex prevention. It is concluded that there is a necessity of
      applying the comprehensive synecological approach in studying the processes
      occurring in the focal ecosystems, which requires a definite methodological and
      structural rearrangement in science organization.

PMID- 11837207
TI  - [From prion diseases to the problem of aging and death].
AB  - The brain tissue of aging mice shows a factor that stimulates the proliferation
      of cells of glial origin both in primarily trypsinized and inoculated cultures.
      This factor that is likely to be of peptide origin is characterized by pronounced
      accumulation dynamics with increasing age in mammals, by unusually high thermal
      stability and by its possible detection in the brain extracts by means of
      isoelectrofocusing rather than electrophoresis. The author proposes a concept
      under which the brain tissue of aging mammals, including human beings,
      accumulates the factor that is active in stimulating the proliferation of glial
      elements, thus resulting in impairment of neuronal trophism, which can in turn be
      a cause of their death and, in the long run, a cause of death of the brain and
      the whole body.

PMID- 11837208
TI  - [Role of works of S. V. Prozorovskii in solving problems of persistence of wall
      free forms of microorganisms].
AB  - S. V. Prozovsky's works are of general biological significance as they show that
      there can be most bacteria that are two forms having various structural
      arrangements: one bacteria have a wall, the others have no, such as L-form ones.
      The paper shows the importance of persistence of bacteria as L-forms in the
      pathogenesis of different infectious diseases. Mechanisms that determine the long
      term persistence of Mycoplasmas in the infected organisms are explored.

PMID- 11837209
TI  - [New and emerging rickettsial and bartonella infections].
AB  - There have been recently reports on over 10 new and resurgent rickettsioses and
      bartonelloses in different countries, which reflects both socioeconomic processes
      in society and a higher methodological level of indication and identification of
      causative agents. In 1991, the author' laboratory, N. F. Gamaleya Research
      Institute of Experimental Medicine, Russian Academy of Medical Sciences,
      established the etiology of the new rickettsiosis Astrakhan spotted fever. It
      separated and studied 2 strains of Rickettsia sp. nov. from patients and 8 ones
      from the carrier the Ixodes tick Rhipicephalus pumilio. It is suggested that the
      natural focus has transformed to the anthropurgic one due to technogenic
      environmental pollution. The annual increase in morbidity rates (2000 cases in
      1983 to 2000) and its area are a challenge to public health care and medical
      science. The paper presents data on the new bartonellosis cat-scratch disease
      (caused by Bartonella henselae) detected not only in Russia. There is also
      information on tick-borne rickettsiosis, epidemic typhus, and trench fever as
      resurgent infections.

PMID- 11837210
TI  - Looking back and moving forward.

PMID- 11837211
TI  - Esophageal cancer. Facts, figures, and screening.
AB  - Over the last 25 years, the incidence of adenocarcinoma of the esophagus has
      increased 350%, faster than any other malignancy in the western world. This
      increase is largely due to gastroesophageal reflux disease and Barrett's
      esophagus. While the current incidence of esophageal cancer is relatively low in
      comparison to other cancers in the United States, this may rapidly change. A cost
      effective screening technique is needed for populations at risk for
      adenocarcinoma of the esophagus. Using unsedated esophagoscopy, gastroenterology
      nurses may be in the best position to coordinate and perform esophageal cancer
      screening for the U.S. population. This article provides an overview of
      esophageal cancer, including types, etiology, symptoms, and diagnosis. In
      addition to an overview of esophageal cancer, this article provides a look at non
      physician, unsedated esophagoscopy as a future direction for esophageal cancer
      screening.

PMID- 11837212
TI  - Development of an outcome/variance tracking tool for sedation and non-surgical
      procedures.
AB  - A large academic cancer center devised a performance improvement plan for special
      procedures and sedation. A group of interdisciplinary professionals convened to
      address data collection, complications, and outcomes for non-surgical procedures
      and sedation. Administrative, medical, and nursing representatives from all areas
      in which these procedures are performed gathered to assess existing data and data
      collection methods and to develop an improvement plan. Gastroenterology,
      pulmonary, diagnostic imaging, intensive care, gynecology, genitourinary,
      hematology, and anesthesiology specialties were represented. The group was
      facilitated by staff from the institution's Office of Performance Improvement and
      co-chaired by an anesthesiologist and a pulmonary specialist. A representative
      from the Practice Outcomes Department was also an active participant. This
      article describes group process, design efforts, pilot testing, and analyses for
      this project. Pilot data are presented as well as a discussion of staff
      involvement.

PMID- 11837213
TI  - Irritable bowel syndrome. A survey of nurses' knowledge.
AB  - Nurses in a variety of clinical settings are often involved in educating and
      managing patients with irritable bowel syndrome, though their knowledge and
      perceptions of irritable bowel syndrome are not well known. A national survey was
      undertaken as a part of a larger study of patients and healthcare providers to
      determine nurses' knowledge of irritable bowel syndrome, including diagnosis,
      etiology, disease impact, management, beliefs, and attitudes regarding irritable
      bowel syndrome. In addition, the nurses' perceptions of the effect of irritable
      bowel syndrome on the patient's lifestyle and the severity of symptoms were
      compared to those of irritable bowel syndrome patients. One hundred practicing
      registered nurses were randomly selected and then interviewed by telephone using
      a questionnaire. A random-digit dialing method was used to identify and recruit
      1,014 women with irritable bowel syndrome. The majority of registered nurses
      interviewed (75%) felt that nurses played a moderate-to-major role in counseling
      patients with irritable bowel syndrome. Only 13%, however, were aware of the
      diagnostic criteria for irritable bowel syndrome. The majority of nurse subjects
      felt the current therapies for irritable bowel syndrome had limited effectiveness
      varying from 6-21% depending on the symptom being treated. Almost half of the
      nurses felt they had an important role in management of irritable bowel syndrome
      and that both they and their patients needed more education about irritable bowel
      syndrome. There was close agreement between the nurses and the patients with
      regard to the impact of irritable bowel syndrome. With increased public attention
      on irritable bowel syndrome as a common problem affecting women, there is a need
      for nurses working in a variety of settings to have increased knowledge regarding
      the syndrome. In this article, recommendations are made regarding how to increase
      nurses' knowledge about this common health problem.

PMID- 11837214
TI  - Work outcomes for female liver transplant recipients with alcohol-related liver
      disease.
AB  - The purpose of this retrospective survey was to describe post-liver transplant
      work outcomes for female liver transplant recipients with histories of alcohol
      related liver disease. The theoretical framework guiding the study was Laffrey's
      conception of health. The Short Michigan Alcohol Screening Test was used to
      measure alcohol-related liver disease. Forty-seven female liver transplant
      recipients whose Short Michigan Alcohol Screening Test scores were indicative of
      alcohol-related liver disease comprised the convenience sample. Using a mailed
      questionnaire, post-transplant work and daily activities were assessed. Work was
      operationally defined as including either employment or household work. Results
      revealed that 59% of the female recipients were working post-transplant and that
      working recipients had higher conception of health scores than did non-working
      recipients.

PMID- 11837215
TI  - Flexible endoscopes: structure and function. The mechanical system.
AB  - Flexible endoscopes are complex medical instruments that are easily damaged. In
      order to maintain flexible endoscopes in optimum working condition, users must
      have a thorough understanding of the structure and function of the instrument.
      This is the third in a series of articles presenting an in-depth look at the care
      and handling of flexible endoscopes. The first articles discussed the air-water
      and the suction channels systems. This article will focus specifically on the
      mechanical system.

PMID- 11837216
TI  - Debate and evaluation of various methods of endoscope reprocessing.

PMID- 11837217
TI  - Looking back or looking all around: comparing two spell checking strategies for
      documents edition in an electronic patient record.
AB  - We report on the comparison of two systems for correcting spelling errors
      resulting in non-existent words (i.e. not listed in any lexicon). Both systems
      aim at improving edition of medical reports. Unlike traditional systems, based on
      word language models, both semantic and syntactic contexts are considered here.
      Both systems share the same string-to-string edit distance module, and the same
      contextual disambiguation principles. The differences between the two systems are
      located at the user interaction level: while the first system is using
      exclusively the left context, simulating the underlining of every mis-spelling at
      the end of every word typing, the second system uses the left as well as the
      right context and simulate a post-edition correction, when asked by the author.
      Our conclusion shows the improvements brought by the second approach.

PMID- 11837218
TI  - Generation of dynamically configured check lists for intra-operative problems
      using a set of covering algorithms.
AB  - We present a prototype of a decision support system for anesthesia that applies
      set covering theory. The system is designed to generate dynamically configured
      check-lists for intra-operative problems. These lists have the potential to help
      anesthesiologists detect and manage problems in a timely manner. The items in the
      lists consist of major complications that should be considered for a particular
      case. A set covering algorithm that accommodates multiple problem sets was used
      to implement the prototype. A simulated case and the system behavior are
      presented. The ultimate goals of a system such as the one presented are to
      function as an intelligent alarm module for electronic monitors and to facilitate
      the task of correcting intra-operative problems.

PMID- 11837219
TI  - Structure localization in brain images: application to relevant image selection.
AB  - Recent advances in imaging have lead to increases in the number of images/study.
      Automated methods to select relevant images are critical to effectively convey
      study results. The proposed method combines natural language processing (NLP) and
      automatic structure localization to identify relevant images of a MR brain study.
      NLP extracts relevant locations of findings. Two algorithms were implemented and
      evaluated for structure localization. The first method involves registration of
      patient dataset to a labeled atlas. The second method involves an eigenimage
      search using a training set of images. A prototype was developed and tested on MR
      brain studies of nine patients. With the registration method, slices containing
      the relevant structure agreed with expert selection in 98% of cases. Structure
      localization by eigenimage search was able to locate the lateral ventricles
      correctly in all the test cases. The proposed method provides an accurate method
      for identifying relevant slices of an imaging study.

PMID- 11837220
TI  - Crohn's disease is caused by mutations in the bacterial response protein NOD2.

PMID- 11837221
TI  - New Food and Drug Administration-based oversight over genetic testing.

PMID- 11837222
TI  - Fortress around the heart.

PMID- 11837223
TI  - [The basic and clinical aspects of pulmonary carcinoma].

PMID- 11837224
TI  - [Obstacles in the clinical study of acute renal failure].

PMID- 11837225
TI  - Identification of sleep-disordered breathing in children: variation with event
      definition.
AB  - STUDY OBJECTIVES: To determine the effect of varying approaches to the
      measurement of the respiratory disturbance index (RDI) on identification of sleep
      disordered breathing (SDB) in children. DESIGN: Cross-sectional study of SDB in a
      well-characterized birth cohort (stratified for term and preterm birth)
      participating in longitudinal studies of cognition and behavior. SETTING:
      Community-based; overnight studies conducted in participant's homes.
      PARTICIPANTS: 433 children, ages 8-11 years, un-referred for clinical assessment
      of SDB. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Participants underwent
      unattended overnight in-home recording of respiratory inductance plethysmography,
      pulse oximetry, body position, and heart rate. The relationships among RDIs
      derived from various definitions of apnea and hypopneas and thresholds for
      frequency of events were assessed. Median RDI varied by more than 20-fold for
      definitions using the more liberal criteria for event definition (all respiratory
      events; i.e., central or obstructive events and hypopneas with no requirement for
      associated desaturation) to the most conservative definition (using obstructive
      apneas only or obstructive apnea and hypopneas requiring a 5% associated
      desaturation). Prevalence estimates for SDB based on RDIs that included central
      apneas were 40% to 140% higher than those that excluded central apneas.
      CONCLUSIONS: Different approaches for quantifying RDI contribute to substantial
      variability in identification and classification of SDB in children and will lead
      to discrepant estimates of its presence and severity.

PMID- 11837226
TI  - Unilateral renal agenesis associated with additional congenital abnormalities of
      the urinary tract in a Pekingese bitch.
AB  - An eight-month-old Pekingese bitch with urinary incontinence was found to have
      three congenital anomalies of the urinary tract: left renal agenesis, bilateral
      ectopic ureters with a left cranial blind-ending ureter, and urinary bladder
      hypoplasia. The diagnoses were made by retrograde vaginourethrography, excretory
      urography, ultrasonography and duplex Doppler ultrasonography. Although
      urological anomalies associated with renal agenesis have been frequently
      observed, a cranial blind-end ectopic ureter has not, to the authors' knowledge,
      been described in the bitch. The dog was managed medically with a restricted
      protein diet because of a compromised unilateral kidney with hydronephrosis and
      hydroureter.

PMID- 11837228
TI  - [Internet and data bases as a part of physician's daily work at the community
      health center].

PMID- 11837227
TI  - Interaction between smoking and the Sstl polymorphism of the apo C-III gene
      determines plasma lipid response to diet.
AB  - BACKGROUND: It has recently been demonstrated that the lipid profile of smokers
      improves if they follow a Mediterranean diet. AIM: To establish whether the Sstl
      polymorphism of the apo C-III gene interacts with smoking and determines the
      lipid response to diet in healthy subjects. METHODS AND RESULTS: Fifty-nine
      volunteers (18 smokers: 8 with the S1S1 genotype, and 10 with the S2 allele; 41
      non-smokers: 29 with the S1S1 genotype and 12 with the S1S2 genotype)
      consecutively followed three different diets: a diet enriched in saturated fatty
      acids (SFA) (38% fat, 20% SFA) followed by a randomised, cross-over period during
      which they ate a diet enriched in carbohydrates (NCEP-1) (30% fat, 10% SFA, 55%
      carbohydrates) and a diet enriched in monounsaturated fatty acids (MUFA) (8% fat,
      22% MUFA). Cholesterol, triacylglycerol, LDL-cholesterol (LDL-C) and HDL
      cholesterol (HDL-C) levels were measured at the end of each dietary period. The
      smokers carrying the S1S1 genotype were not influenced by any of the diets, but
      the atherogenic ratio decreased in the carriers of the S2 allele when they
      changed from the diet rich in SFA to a diet rich in olive oil or carbohydrates (p
      < 0.039). No significant difference was observed when the non-smoking carriers of
      the S2 allele changed from one diet to another, but there was a decrease in the
      LDL-C/HDL-C ratio when the subjects with the S1S1 genotype changed from the
      saturated diet to either of the other diets (p < 0.001). CONCLUSIONS: Smoking
      interacts with the apo CM polymorphism and determines the level of lipid response
      to dietary changes.

PMID- 11837230
TI  - Influence of N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid pH buffer on the
      biological response of marine algae.
AB  - The N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES) is extensively
      used as pH buffer in culture media for testing chemicals. However, this study
      demonstrates that 0.01 M HEPES significantly reduces the rate of Cu, Pb, and Cd
      binding to Porphyra spp. and Enteromorpha spp. marine macroalgae. The HEPES also
      decreased the accumulation of Cu, Pb, and Cd but not Hg by these macroalgae. Both
      the extracellular adsorption and the intracellular uptake of the metals were
      influenced by HEPES to a similar extent. The HEPES also promoted the release of
      exudates by the algae, and these exudates form very stable complexes with Cu (and
      probably with other trace metal ions). The HEPES interference varied with the
      nature of the metal, the macroalga, and the season. The presence of 0.01 M HEPES
      in seawater cultures of the Emiliania huxleyi (a microalga) also interfered with
      E. huxleyi growth, liberation of Cu-complexing organic ligands, and Cu uptake.
      The HEPES, which displays surface activity, may facilitate the binding of metals
      to the algae for an initial exposure period. The metal taken up appears to
      stimulate the liberation of exudates that subsequently control the
      bioavailability of the metals and therefore metal uptake. Because HEPES can
      control the uptake of trace metals by algae and the production of organic
      ligands, the results obtained in cultures containing the HEPES pH buffer can be
      influenced by this component of the media.

PMID- 11837229
TI  - Biomimetic solid-phase microextraction to predict body residues and toxicity of
      chemicals that act by narcosis.
AB  - A biomimetic extraction technique using solid-phase microextraction (SPME) fibers
      has been developed for the risk assessment of contaminants with a narcotic mode
      of action. Our goal is to apply this technique in the future for the prediction
      of total baseline toxicity of environmental water and effluent samples.
      Validation of this method requires establishing the relationship between
      contaminant accumulation and toxicity in biota and accumulation in the surrogate
      solid phase (the SPME fiber coating). For this purpose, we determined the median
      lethal concentration (LC50) values for Chironomus riparius midge larvae exposed
      to two halogenated aromatic compounds separately and measured body residues in
      the exposed larvae. Solid-phase microextraction fibers with an 85-microm
      polyacrylate (PA) coating served as the surrogate hydrophobic phase, mimicking
      the uptake of the compounds by midge larvae. The toxicant concentrations in SPME
      fibers measured directly by gas chromatography/mass spectrometry (GC-MS) or
      calculated from the SPME fiber-water partition coefficient, K(SPME) were related
      to the toxicant concentrations found in midge larvae. Our results demonstrated
      that the biomimetic SPME method enables the estimation of body residues in biota
      and prediction of the degree of baseline toxicity of a water medium.

PMID- 11837231
TI  - Toxaphene and other persistent organochlorine pesticides in three species of
      albatrosses from the north and south Pacific Ocean.
AB  - Toxaphene and other persistent organochlorine (OC) pesticides (chlordane-related
      compounds [sigmaCHL], DDT-related compounds [sigmaDDT], hexachlorocyclohexanes
      [sigmaHCH], tris(p-chloro-phenyl)methane, hexachlorobenzene, octachlorostyrene,
      dieldrin) were determined in fat of Laysan albatross (Diomedea immutabilis) and
      in fat and eggs of blackfooted albatross (Diomedea nigripes) from the central
      north Pacific Ocean. The HCH isomers and chlordane- and DDT-related compounds
      were also determined in eggs of northern royal albatross (Diomedea sanfordi)
      collected in New Zealand. Toxaphene was detected in fat samples at mean +/-
      standard deviation (SD) levels ranging from 243 +/- 61 ng/g wet weight in Laysan
      albatross to 1,020 +/- 237 ng/g wet weight in blackfooted albatross. These levels
      were higher than sigmaCHL and sigmaHCH but lower than sigmaDDT. In eggs of
      blackfooted albatross, toxaphene was the major OC pesticide, averaging 513 ng/g
      wet weight in two pooled samples compared with 293 ng/g wet weight for sigmaDDT.
      Two toxaphene congeners, the octachloroborane B8-1413 (Parlar 26) and the
      nonachlorobornane B9-1679 (P50), comprised about 38% of total toxaphene in both
      albatross species. All OC compounds were present at significantly higher levels
      in blackfooted than Laysan albatross fat with the exception of sigmaHCH,
      dieldrin, and octachlorostyrene. Mean levels of sigmaDDT and sigmaHCH in northern
      royal albatross eggs from New Zealand were 4 and 60 times lower, respectively,
      than in blackfooted albatross eggs. The pattern of OC pesticide accumulation was
      consistent with differences in distribution of the three species in the Pacific
      Ocean, with highest levels in blackfooted albatross, which feed off the west
      coast of North America, intermediate levels in Laysan albatross, which frequent
      the western Pacific, and lowest levels in northern royal albatross, which are
      confined to the southern oceans surrounding the Antarctic.

PMID- 11837232
TI  - Combined effects of lowered oxygen and toxicants (copper and diazinon) on the
      mayfly Ephoron virgo.
AB  - In many large European rivers, the number of typical riverine insect species,
      such as mayflies, stoneflies, and caddisflies, is greatly reduced compared to
      historic records. This can no longer be explained by high concentrations of a
      relatively small number of dominant toxicants since many rivers have changed from
      heavily contaminated systems with a few selected key toxicants to systems with a
      complex contamination. This contamination consists of many substances in low
      concentrations coinciding with other unfavorable conditions, such as low oxygen
      concentrations. It was hypothesized that the joint adverse effects of such
      multiple stressors may be a steering factor in the distribution of riverine
      insect species. The aim of this study was therefore to determine the combined
      effects of toxicants and oxygen depletion. To this purpose, larvae of the
      indigenous riverine mayfly Ephoron virgo were exposed to two different model
      toxicants, copper and diazinon, under normoxia and hypoxia (50% air saturation)
      conditions. The median effective concentrations for mortality for copper were
      significantly lower in the hypoxia treatments than in the normoxia treatments.
      For diazinon, no differences were observed between two treatments differing in
      dissolved oxygen levels, and therefore we argue that interactions between
      multiple stressors may be compound specific. It is concluded that the combination
      of toxicants and lowered oxygen may have a stronger impact than can be expected
      based on the adverse effects of the individual factors and that standard toxicity
      tests may be insufficient alone to determine the impact of human activities on
      the ecological state of riverine communities. Instead, attention needs to be paid
      to more environmentally realistic nonoptimal conditions in toxicity testing to
      adequately fulfill the needs of ecological recovery programs.

PMID- 11837233
TI  - Benzo[a]pyrene absorption and exposure pathways in the green mussel Perna
      viridis.
AB  - The absorption efficiency (AE) of benzo[a]pyrene (BaP), a representative
      polycyclic aromatic hydrocarbon compound, in the green mussel Perna viridis was
      measured under different biological and food conditions (body size, food
      quantity, and food species). Uptake of BaP from the aqueous phase by different
      species of phytoplankton and green mussels was also experimentally quantified. A
      bioenergetic-based kinetic model was then used to separate the exposure pathways
      of BaP accumulation in the green mussels. Our results demonstrated that the AE of
      BaP in the green mussels ranged between 17 and 47%. Body size did not
      significantly affect the AE of BaP in the mussels. The AEs increased with a
      decrease in food availability, largely as a result of lengthening the gut passage
      of chemicals. The AEs differed by up to 2.3 times (17-39%) among the different
      food diets tested (four phytoplankton diets and one sediment diet). The BaP
      associated with the sediment was assimilated least efficiently. The difference in
      gut passage also appeared to account partially for the difference in AEs observed
      among different food types. No correlation between the AE and the distribution of
      BaP in the cytoplasm of phytoplankton cells was found. The concentration factor
      of BaP measured in four different marine phytoplankton species was in the range
      of 10(4)-5 x 10(4) (L/kg). The calculated uptake rate constant of BaP in the
      green mussels was 6.37 L/g/d, and the efficiency of absorption of BaP from the
      aqueous phase was 6.6 to 8.8%. The model calculation indicated that under most
      circumstances, >56% of BaP in mussels can indeed be derived from the uptake from
      the aqueous phase. However, the relative importance of aqueous and dietary
      exposure can be affected by the variation of AE, mussel's ingestion rate, and
      concentration of BaP in ingested food particles.

PMID- 11837234
TI  - Using a biology-based model (DEBtox) to analyze bioassays in ecotoxicology:
      opportunities and recommendations.
AB  - The conventional analysis of bioassays does not account for biological
      significance. However, mathematical models do exist that are realistic from a
      biological point of view and describe toxicokinetics and effects on test
      organisms of chemical compounds. Here we studied a biology-based model (DEBtox)
      that provides an estimate of a no-effect concentration, and we demonstrated the
      ability of such a model to adapt to different situations. We showed that the
      basic model can be extended to deal with problems usually faced during bioassays
      like time-varying concentrations or unsuitable choices of initial concentrations.
      To reach this goal, we report experimental data from Daphnia magna exposed to
      zinc. These data also showed the potential benefit of the model in understanding
      the influence of food on toxicity. We finally make some recommendations about the
      choice of initial concentrations, and we propose a test with a depuration period
      to check the relevance and the predictive capacity of the DEBtox model. In our
      experiments, the model performed well and proved its usefulness as a tool in risk
      assessment.

PMID- 11837235
TI  - Monitoring land-use change effects on soil carbon in New Zealand: quantifying
      baseline soil carbon stocks.
AB  - We designed a soil carbon monitoring system for New Zealand using country
      specific land use and soil carbon information. The system pre-stratifies the
      country by soil type, climate, and land use. Soils were placed in six IPCC soil
      categories; Podzols were added as they are widespread throughout New Zealand.
      Temperature was stratified into two categories, each spanning 7 degrees C.
      Moisture categories were based on water balance, and included five categories.
      Temperature and moisture stratification was based on the USDA Soil Classification
      system. Land use (10 categories) was based on 1980s survey data. Overall, 39
      combinations of these three factors (cells) described 93% of the New Zealand
      landscape. Geo-referenced soil carbon data (carbon concentration and bulk
      density) were used to quantify average soil carbon for each of the 39 cells.
      Aggregating the polygons gave an estimated 1990 soil carbon baseline of 1152+/
      44, 1439+/-73, and 1602+/-167 Mt C (mean+/-S.D.) for the 0-0.1, 0.1-0.3, and 0.3
      1.0 m depth increments (not including forest floor carbon). The system described
      could also be used to quantify equilibrium changes in soil C associated with land
      use change if land use is updated periodically.

PMID- 11837236
TI  - Effects of forest management on soil carbon: results of some long-term resampling
      studies.
AB  - The effects of harvest intensity (sawlog, SAW; whole tree, WTH; and complete
      tree, CTH) on biomass and soil C were studied in four forested sites in the
      southeastern US (mixed deciduous forests at Oak Ridge, TN and Coweeta, NC; Pinus
      taeda at Clemson, SC: and P. eliottii at Bradford, FL). In general, harvesting
      had no lasting effects on soil C. However, intensive temporal sampling at the NC
      and SC sites revealed short-term changes in soil C during the first few years
      after harvesting, and large, long-term increases in soil C were noted at the TN
      site in all treatments. Thus, changes in soil C were found even though lasting
      effects of harvest treatment were not. There were substantial differences in
      growth and biomass C responses to harvest treatments among sites. At the TN site,
      there were no differences in biomass at 15 years after harvest. At the SC site,
      greater biomass was found in the SAW than in the WTH treatment 16 years after
      harvest, and this effect is attributed to be due to both the N left on site in
      foliar residues and to the enhancement of soil physical and chemical properties
      by residues. At the FL site, greater biomass was found in the CTH than in the WTH
      treatment 15 years after harvest, and this effect is attributed to be due to
      differences in understory competition. Biomass data were not reported for NC. The
      effects of harvest treatment on ecosystem C are expected to magnify over time at
      the SC and FL sites as live biomass increases, whereas the current differences in
      ecosystem C at the TN site (which are due to the presence of undecomposed
      residues) are expected to lessen with time.

PMID- 11837237
TI  - Local-scale fluxes of carbon dioxide in urban environments: methodological
      challenges and results from Chicago.
AB  - Much attention is being directed to the measurement and modeling of surface
      atmosphere exchanges of CO2 for different surface types. However, as yet, few
      measurements have been conducted in cities, even though these environments are
      widely acknowledged to be major sources of anthropogenic CO2. This paper
      highlights some of the challenges facing micrometeorologists attempting to use
      eddy covariance techniques to directly monitor CO2 fluxes in urban environments,
      focusing on the inherent variability within and between urban areas, and the
      importance of scale and the appropriate height of measurements. Results from a
      very short-term study of CO2 fluxes, undertaken in Chicago, Illinois in the
      summer of 1995, are presented. Mid-afternoon minimum CO2 concentrations and
      negative fluxes are attributed to the strength of biospheric photosynthesis and
      strong mixing of local anthropogenic sources in a deep mixed layer. Poor night
      time atmospheric mixing, lower mixed layer depths, biospheric respiration, and
      continued missions from mobile and fixed anthropogenic sources, account for the
      night-time maxima in CO2 concentrations. The need for more, longer-term,
      continuous eddy covariance measurements is stressed.

PMID- 11837238
TI  - Pacifier as a risk factor for acute otitis media.

PMID- 11837239
TI  - Pacifier as a risk factor for acute otitis media.

PMID- 11837240
TI  - Pacifier as a risk factor for acute otitis media.

PMID- 11837241
TI  - Ecological-friendly pigments from fungi.
AB  - The dyestuff industry is suffering from the increases in costs of feedstock and
      energy for dye synthesis, and they are under increasing pressure to minimize the
      damage to the environment. The industries are continuously looking for cheaper,
      more environmentally friendly routes to existing dyes. The aim of this minireview
      is to discuss the most important advances in the fungal pigment area and its
      interest in biotechnological applications. Characteristic pigments are produced
      by a wide variety of fungi and the chemical composition of natural dyes are
      described. These pigments exhibit several biological activities besides
      cytotoxicity. The synthetic pigments authorized by the EC and in USA and the
      natural pigments available in the world market are discussed. The obstacle to the
      exploitation of new natural pigments sources is the food legislation, requesting
      costly toxicological research, manufacturing costs, and acceptance by consumers.
      The dislike for novel ingredients is likely to be the biggest impediment for
      expansion of the pigment list in the near future. If the necessary toxicological
      testing and the comparison with accepted pigments are made, the fungal pigments,
      could be acceptable by the current consumer. The potentiality of pigment
      production in Brazil is possible due to tremendous Amazonian region biodiversity.

PMID- 11837242
TI  - Core foods of the US food supply.
AB  - The core food dietary intake/exposure model may be used to assess the average
      intake of nutrients, contaminants and other food components by a population group
      and various subgroups of the population. The core food model is a mechanism that
      allows for the selection of the most important foods in a population's food
      supply so that these foods can be obtained and analysed in the laboratory. The
      core foods for a population change over time as food consumption patterns are
      altered by changes in the food supply and/or changes in the demographics of the
      population. Core foods of the US diet were selected using food consumption data
      from the 1994-96 US Department of Agriculture (USDA) Continuing Survey of the
      Food Intake of Individuals (CSFII). The 304 core foods were identified by placing
      the 5722 foods consumed by survey participants into about 300 groups. The
      groupings were based on food type, food use and similarity of nutrient
      composition. The foods within each grouping were ranked in terms of frequency of
      use and weight of intake, and one food item within each group was selected to
      become a core food and represent its group. In the model, each core food assumes
      the full dietary intake (by weight) for all the foods in its group. Daily mean
      intakes of the 304 selected core foods are presented for women and men of 19-30
      years of age. If the food components of interest to investigators using this
      model are found in selected foods or food types, then only these foods need be
      analysed. The list of 304 core foods may be shortened by further aggregation to
      match the needs of different investigators. For example, limited data on food
      composition may warrant use of a shorter core food list. A shortened food list
      with average daily intakes of 78 core foods for women and men of 19-30 years of
      age is provided as an example.

PMID- 11837243
TI  - Influence of flavour absorption on oxygen permeation through LDPE, PP, PC and PET
      plastics food packaging.
AB  - The effect of flavour absorption on the oxygen permeability of low-density
      polyethylene (LDPE), polypropylene (PP), polycarbonate (PC) and polyethylene
      terephthalate (PET) was studied using an isostatic continuous flow system.
      Polymer samples were exposed to a model solution containing limonene, hexyl
      acetate, nonanone and decanal at 40 degrees C. After exposure, one part of each
      sample was analysed for absorbed flavour compounds using a Large Volume Injection
      GC Ultrasonic 'in vial' extraction method, and from the other part, oxygen
      permeability was measured in a permeation cell at 25 degrees C. After 8 h of
      exposure, LDPE and PP samples showed a significant linear (R2 = 0.82 and 0.99)
      increase in oxygen permeability of 21 and 130%, respectively. Owing to swelling
      of the polymer samples resulting from flavour absorption, the structure of the
      polymeric network changed (i.e. opened) and consequently increased oxygen
      permeability. The oxygen permeability of exposed PC showed a significant linear
      (R2 = 0.78) decrease of 11% after 21 days. PC obviously did not swell like LDPE
      or PP. Therefore, it was suggested that absorbed flavour compounds occupied or
      blocked 'microcavities' through which normally oxygen is transported. Absorption
      of flavour compounds by PET did not affect the oxygen permeability of PET
      significantly.

PMID- 11837244
TI  - Combination of alpha-stat strategy and hemodilution exacerbates neurologic injury
      in a survival piglet model with deep hypothermic circulatory arrest.
AB  - BACKGROUND: The optimal pH strategy and hematocrit during cardiopulmonary bypass
      with deep hypothermic circulatory arrest (DHCA) remain controversial. We studied
      the interaction of pH strategy and hematocrit and their combined impact on
      cerebral oxygenation and neurological outcome in a survival piglet model
      including monitoring by near-infrared spectroscopy (NIRS). METHODS: Thirty-six
      piglets (9.2+/-1.1 kg) underwent DHCA under varying conditions with continuous
      monitoring by NIRS (pH-stat or alpha-stat strategy, hematocrit 20% or 30%, DHCA
      time 60, 80, or 100 minutes). Neurological recovery was evaluated daily. The
      brain was fixed in situ on postoperative day 4 and a histological score (HS) for
      neurological injury was assessed. RESULTS: Oxygenated hemoglobin (HbO2) and total
      hemoglobin signals detected by NIRS were significantly lower with alpha-stat
      strategy during cooling (p < 0.001), suggesting insufficient cerebral blood
      supply and oxygenation. HbO2 declined to a plateau (nadir) during DHCA. Time to
      nadir was significantly shorter in lower hematocrit groups (p < 0.01).
      Significantly delayed neurologic recovery was seen with alpha-stat strategy
      compared with pH-stat (p < 0.05). The alpha-stat group had a worse histological
      score compared with those assigned to pH-stat (p < 0.001). Neurologic impairment
      was estimated to be over 10 times more likely for animals randomized to alpha
      stat compared with pH-stat strategy (odds ratio = 10.7, 95% confidence interval =
      3.8 to 25.2). CONCLUSIONS: Combination of alpha-stat strategy and lower
      hematocrit exacerbates neurological injury after DHCA. The mechanism of injury is
      inadequate cerebral oxygenation during cooling and a longer plateau period of
      minimal O2 extraction during DHCA.

PMID- 11837245
TI  - Pneumomediastinum during spontaneous vaginal delivery.
AB  - We report two rare cases of spontaneous pneumomediastinum that presented shortly
      after childbirth and resolved without treatment. Spontaneous pneumomediastinum
      has been described in a wide range of seemingly unrelated but recurrent clinical
      scenarios. We highlight their common etiologic factors and provide the anatomic
      and physiologic bases for the radiologic signs that are common in all these
      conditions.

PMID- 11837246
TI  - Postoperative fluorescence bronchoscopic surveillance: a worthwhile procedure in
      a subset of patients.

PMID- 11837247
TI  - Surgical repair of supposedly multiple defects within the apical part of the
      muscular ventricular septum.
AB  - BACKGROUND: A distinct defect has been described within the apical part of the
      muscular ventricular septum, which has multiple orifices when seen from its right
      ventricular aspect. Closure has been suggested using umbrella devices introduced
      on a catheter. Such an intervention, however, can be technically difficult in
      small infants. METHODS: We have recently seen two examples of this type of
      complex communication between the apexes of both left and right ventricles.
      Neither could be closed by catheterization. A surgical approach was used through
      a modified apical right ventriculotomy. We have also studied two autopsied
      specimens, which clarify the morphologic arrangement. RESULTS: Both patients were
      closed successfully, with trivial residual shunt and good biventricular
      functions. The patients were clinically well at 2-year follow-up. CONCLUSIONS:
      Surgical division of right ventricular trabeculations makes it feasible to
      identify and repair the septal deficiency, which is a solitary hole. On the basis
      of our morphologic study, we offer an explanation for the anatomic arrangement
      that differs from the one proposed by recent previous investigators. If the
      ventricular incision is appropriately placed, our anatomic studies suggest that
      it is possible to visualize the solitary opening from its right ventricular
      aspect, and achieve surgical closure with a single patch.

PMID- 11837248
TI  - Effect of hydrogen peroxide and sodium perborate on biomechanical properties of
      human dentin.
AB  - This study compared the ultimate tensile strength, micropunch shear strength, and
      microhardness of bleached and unbleached human dentin. Forty-four intact
      premolars were root canal treated and randomly divided into four groups.
      Bleaching agents were sealed in pulp chambers, as in clinical use. Group 1
      (control) was treated with water, group 2 with 30% hydrogen peroxide, group 3
      with sodium perborate mixed with water, and group 4 with sodium perborate mixed
      with 30% hydrogen peroxide. The teeth were stored in saline at 37 degrees C for 7
      days. The teeth were then sectioned and biomechanical tests were carried out on
      dentin specimens that were obtained from all teeth. Intracoronal bleaching with
      30% hydrogen peroxide and sodium perborate used either alone or in combination
      weakened dentin. Hydrogen peroxide alone tended to be more damaging than sodium
      perborate used alone or sodium perborate mixed with hydrogen peroxide.

PMID- 11837249
TI  - Discrepancies between chained and classic utilities induced by anchoring with
      occasional adjustments.
AB  - BACKGROUND: Classic utility assessment uses death and perfect health as end
      points. Chained utility assessment uses other health states as endpoints. It has
      been previously noted that these 2 assessment procedures lead to different
      utilities. PURPOSE: The author attempts to explain these discrepancies between
      chained and classic assessments. METHOD: Previous data are plotted in a uniform
      way to facilitate comparison. Using time trade-off and paired-comparison data,
      the author estimates the extent to which respondents adjust their responses when
      end points are varied. Data were obtained in various samples: in healthy
      volunteers from the general public, in students, and in women at high risk for
      breast cancer seeking genetic counseling. RESULTS: The author obtained 741 valid
      data records from a total of 106 participants. The data replicate the pattern
      found previously. When compared to classic utilities, (1) chained utilities are
      smaller (larger) when the best (worst) endpoint varies and (2) the discrepancies
      become smaller for utilities near 0 and 1. The data reveal that there is a
      distinct failure to adjust responses when the end points are varied, as if the
      responses anchor on some master health scale. The latter finding explains the
      robust pattern of discrepancies. CONCLUSION: Decision analyses that use a mix of
      classic and chained utilities are not on firm ground. One should be wary of
      normative interpretations of new value assessment procedures. Alternative
      interpretations of the findings are discussed.

PMID- 11837250
TI  - Role of bradykinin in acid-induced mesenteric hyperemia and duodenal villous
      damage.
AB  - Intestinal mucosal capsaicin-sensitive afferent nerves mediate, in part, the
      mesenteric hyperemia after intraduodenal acidification. The hyperemia plays a
      role in protecting the duodenal mucosa against acid damage. We tested the
      hypothesis that bradykinin contributes to this protective hyperemia. A specific
      antagonist of bradykinin will attenuate the hyperemia and exacerbate duodenal
      villous damage induced by acid. Study 1: Intravenous vehicle, or the specific
      bradykinin B2 receptor antagonist (HOE 140) was administered to anesthetized
      rats. This was followed by intraduodenal bolus administration of 160 microM
      capsaicin or 0.1 N HCl, and then intravenous bradykinin. Study 2: Intravenous
      administration of vehicle or HOE 140 was followed by duodenal perfusion with 0.1
      N HCl. Superior mesenteric artery blood flow (pulsed Doppler flowmetry) (Study 1)
      and duodenal villous damage (histology) (Study 2) were recorded. HOE 140
      significantly reduced the hyperemia induced by bradykinin and intraduodenal
      capsaicin or acid. Deep villous injury was significantly increased after
      treatment with HOE 140. These findings support the hypothesis that acid-induced
      and afferent nerve-mediated mesenteric hyperemia is modulated by a mechanism that
      involves bradykinin B2 receptor. Antagonism of bradykinin B2 receptor also
      increased acid-induced deep duodenal villous damage. Thus, maintenance of
      bradykinin-mediated mesenteric hyperemia, is a previous unrecognized mechanism
      associated with protection of the rat duodenal mucosa against acid-induced
      damage.

PMID- 11837251
TI  - Growth inhibitory activity of lemnabourside on human prostate cancer cells.
AB  - Induction of apoptosis and androgen ablation are two major approaches for
      treating human prostate carcinoma. In a study of the bioactive components of the
      soft coral Nephthea chabroli, we found that lemnabourside is a 5alpha-reductase
      inhibitor, as shown by its ability to inhibit the conversion of testosterone into
      the more potent dihydrotestosterone in rat prostate homogenate. The compound also
      inhibited the incorporation of tritiated thymidine into human prostate androgen
      dependent carcinoma LNCaP cells, and thus blocking the cell proliferation (IC50 =
      37.5 microM). The expression of prostate marker genes, including 5alpha
      reductase, prostate-specific antigen, prostatic acid phosphatase and androgen
      receptor, and the anti-apoptotic bcl-2 gene were markedly reduced, but the
      transcription of apoptosis-related caspase 3 gene showed a dose-dependent
      increase in lemnabourside-treated LNCaP cells. Immunofluorescent microscopy and
      flow cytometric analysis further demonstrated apoptotic changes in these cells.
      Taken all results together, a relatively weak 5alpha-reductase inhibitory
      activity on LNCaP cells (EC50 > 250 microM), and a similar growth inhibitory
      activity on both androgen dependent- and independent-prostate cells (IC50
      approximately 37.5 microM) indicated that caspase-3 apoptosis pathway is one of
      the possible antiproliferative activities mediated by lemnabourside.

PMID- 11837253
TI  - Morphometric and immunohistochemical characterization of the intimal layer
      throughout the arterial system of elderly humans.
AB  - The purpose of the present study was to obtain insight into the natural
      development of adaptive intimal thickening and atherosclerosis in the arterial
      tree of human species. The morphometry and composition of the intimal layer were
      studied in the arterial system of elderly individuals. Post mortem, a total of
      703 arterial segments were dissected from 24 subjects (age 81.9 +/- 9.9 years).
      From each subject, segments were dissected from 31 different arteries. Area
      stenosis [(plaque area/vessel area) x 100%] was determined in each segment. By
      (immuno)histochemistry, lipid content and the presence of inflammatory cells
      (macrophages) were assessed in the coronary, common carotid, brachial, radial and
      internal iliac arteries. Adaptive intimal thickening or advanced atherosclerosis
      was observed in all studied artery types. Area stenosis was highest in the
      coronary arteries (median, 30%) and lowest in the arteries supplying the brain
      (median, < or = 7%). Plaques hiding a lipid-rich core and plaques with macrophage
      infiltration were observed in all five selected artery types. In summary, the
      present observation demonstrates that intimal thickening is a systemic process
      involving most artery types. Within elderly humans, features of advanced
      atherosclerotic disease, a lipid-rich core and macrophages, can be observed in
      the intimal layer of artery types that are recognised for their relation with
      clinical syndroms as well as artery types that remain clinically silent.

PMID- 11837254
TI  - Production of the next-generation library virtual tour.
AB  - While many libraries offer overviews of their services through their Websites,
      only a small number of health sciences libraries provide Web-based virtual tours.
      These tours typically feature photographs of major service areas along with
      textual descriptions. This article describes the process for planning, producing,
      and implementing a next-generation virtual tour in which a variety of media
      elements are integrated: photographic images, 360-degree "virtual reality" views,
      textual descriptions, and contextual floor plans. Hardware and software tools
      used in the project are detailed, along with a production timeline and budget,
      tips for streamlining the process, and techniques for improving production. This
      paper is intended as a starting guide for other libraries considering an
      investment in such a project.

PMID- 11837252
TI  - Evans Blue Dye as an in vivo marker of myofibre damage: optimising parameters for
      detecting initial myofibre membrane permeability.
AB  - Evans Blue Dye (EBD) is widely used to study cellular membrane permeability and
      has recently been utilised in mdx mice to identify permeable skeletal myofibres
      that have become damaged as a result of muscular dystrophy. EBD has the potential
      to be a useful vital stain of myofibre permeability in other models of skeletal
      muscle injury and membrane-associated fragility. The parameters for its use for
      such purposes were optimised in the present study, of particular interest is the
      use of EBD to identify the onset of muscle damage. This study compared
      intravenous vs. intraperitoneal injection; tissue fixation; volume of EBD; time
      of availability in tissue; and persistence after injection in mdx mice (with
      endogenous muscle damage) and control mice. Satisfactory labelling of permeable
      myofibres was seen in frozen sections viewed with fluorescence microscopy when
      intraperitoneal injection of a 1% EBD solution injected at 1% volume relative to
      body mass was administered between 16 and 24 h prior to tissue sampling. EBD
      labelling was then assessed in three mouse models of experimental injury and
      repair-cut injury, whole muscle grafts, and exercise-induced muscle damage. These
      experiments demonstrated that (i) following a cut injury across myofibres, EBD
      penetrated up to 150 microm from the injury site over a 20-h period; (ii) EBD was
      present throughout myofibres of avascular whole muscle graft by one day after
      transplantation; and (iii) damaged myofibres were detected within 20 min after
      controlled lengthening-contraction exercise. This simple and inexpensive
      technique has sensitivity for the detection of increased myofibre permeability
      and/or sublethal damage that has advantages over other traditional histological
      techniques at the light microscopy level.

PMID- 11837255
TI  - Ensuring quality Website redesign: the University of Maryland's experience.
AB  - The Web Redesign Committee at the Health Sciences and Human Services Library
      (HS/HSL) of the University of Maryland was formed to evaluate its site and
      oversee the site's redesign. The committee's goal was to design a site that would
      be functional, be usable, and provide the library with a more current image.
      Based on a literature review and discussions with colleagues, a usability study
      was conducted to gain a better understanding of how the Website was used.
      Volunteers from across the campus participated in the study. A Web-based survey
      was also used to gather feedback. To complement user input, library staff were
      asked to review the existing site. A prototype site was developed incorporating
      suggestions obtained from the evaluation mechanisms. The usability study was
      particularly useful because it identified problem areas, including terminology,
      which would have been overlooked by library staff. A second usability study was
      conducted to refine the prototype. The new site was launched in the spring of
      2000. The usability studies were valuable mechanisms in designing the site. Users
      felt invested in the project, and the committee received valuable feedback. This
      process led to an improved Website and higher visibility for the library on
      campus.

PMID- 11837256
TI  - Evidence-based practice: extending the search to find material for the systematic
      review.
AB  - BACKGROUND: Cochrane-style systematic reviews increasingly require the
      participation of librarians. Guidelines on the appropriate search strategy to use
      for systematic reviews have been proposed. However, research evidence supporting
      these recommendations is limited. OBJECTIVE: This study investigates the
      effectiveness of various systematic search methods used to uncover randomized
      controlled trials (RCTs) for systematic reviews. Effectiveness is defined as the
      proportion of relevant material uncovered for the systematic review using
      extended systematic review search methods. The following extended systematic
      search methods are evaluated: searching subject-specific or specialized databases
      (including trial registries), hand searching, scanning reference lists, and
      communicating personally. METHODS: Two systematic review projects were
      prospectively monitored regarding the method used to identify items as well as
      the type of items retrieved. The proportion of RCTs identified by each systematic
      search method was calculated. RESULTS: The extended systematic search methods
      uncovered 29.2% of all items retrieved for the systematic reviews. The search of
      specialized databases was the most effective method, followed by scanning of
      reference lists, communicating personally, and hand searching. Although the
      number of items identified through hand searching was small, these unique items
      would otherwise have been missed. CONCLUSIONS: Extended systematic search methods
      are effective tools for uncovering material for the systematic review. The
      quality of the items uncovered has yet to be assessed and will be key in
      evaluating the value of the systematic search methods.

PMID- 11837257
TI  - Comparison of bibliographic databases for information on the rehabilitation of
      people with severe mental illness.
AB  - OBJECTIVE: The research sought to examine the overlap in coverage between several
      health-related databases, thus enabling the identification of the most important
      sources for searching for information on the rehabilitation of people with severe
      mental illness. METHODS: The literature was searched within a systematic review.
      Several health-related databases were retrieved (Cumulative Index to Nursing and
      Allied Health Literature, The Cochrane Library, MEDLINE, PsycLIT, Sociofile, and
      Social Science Citation Index), noting their source and comparing results
      retrieved from each database. FINDINGS: The total number of studies retrieved
      from each database varied. Almost a third of the papers retrieved from each
      database were unique to that source. Forty-two percent of the papers were only
      found in one database. Restricting a search to one database alone would miss many
      papers and could affect the results of a systematic review. PsycLIT was the most
      useful database for this topic area, containing 44% of the papers. MEDLINE, the
      database of first choice for many health professionals, held only 29%.
      CONCLUSIONS: No database was determined to be significantly more useful than any
      other--each warranted inclusion in the study. Reliance cannot be placed on one
      database alone, and other methods such as hand searching should also be used.
      Although this may not be new information for information professionals, it is
      likely to be new for health professionals and researchers who are increasingly
      performing their own literature searches. Information professionals have an
      important role to play in conveying this message to those outside their
      profession.

PMID- 11837258
TI  - Electronic journal access: how does it affect the print subscription price?
AB  - OBJECTIVE: This study examined the rates of print journal subscription price
      increases according to the type of available electronic access. The types of
      access included: electronic priced separately from the print, combination print
      with "free online" access, and aggregated, defined here as electronic access
      purchased as part of a collection. The percentages of print price increases were
      compared to each other and to that for titles available only in print. The
      authors were not aware of prior objective research in this area. METHODS: The
      authors analyzed the percentage print price increases of 300 journals over a five
      year time period. The titles were grouped according to type of available
      electronic access. The median and mean percentage print price increases were
      calculated and plotted for all titles within each group. RESULTS: Using both the
      median and the mean to look at the percentage print price increases over five
      years, it was obvious that print prices for journals with electronic access
      exceeded journals that did not offer an electronic option. Electronic priced
      separately averaged 3% to 5% higher than print only titles using both measures.
      Combination print with "free online" access had higher increases from 1996 to
      1999, but, in 2000, their percentage increases were about the same as print only
      titles. The rate of price increases for aggregated titles consistently went down
      over the past five years. Journals with no electronic option showed the lowest
      percentage rates of print price increase. CONCLUSIONS: The authors' findings
      reveal that the increases of print prices for their sample of titles were higher
      if a type of electronic access was offered. According to the results of this
      study, aggregated collections currently represent the electronic option whose
      percentage price increase for print prices was lowest. However, the uneven
      fluctuations in rates of subscription prices revealed that the pricing of
      journals with electronic access is still evolving. More study is recommended to
      see if the trends observed in this study are sustained over a longer time period.

PMID- 11837259
TI  - Online journals: impact on print journal usage.
AB  - PURPOSE: The research sought to determine the impact of online journals on the
      use of print journals and interlibrary loan (ILL). SETTING: The Library of the
      Health Sciences-Peoria is a regional site of the University of Illinois at
      Chicago (UIC) Library with a print journal collection of approximately 400
      titles. Since 1999, UIC site licenses have given students and faculty affiliated
      with UIC-Peoria access to more than 4,000 online full-text journal titles through
      the Internet. METHODOLOGY: The Library of the Health Sciences-Peoria has
      conducted a journal-use study over an extended period of time. The information
      collected from this study was used to assess the impact of 104 online journals,
      added to the collection in January 1999, on the use of print journals. RESULTS:
      Results of the statistical analysis showed print journal usage decreased
      significantly since the introduction of online journals (F(1,147) = 12.10, P <
      0.001). This decrease occurred regardless of whether a journal was available only
      in print or both online and in print. Interlibrary loan requests have also
      significantly decreased since the introduction of online journals (F(2,30) =
      4.46, P < 0.02). CONCLUSIONS: The decrease in use of the print collection
      suggests that many patrons prefer to access journals online. The negative impact
      the online journals have had on the use of the journal titles available only in
      print suggests users may be compromising quality for convenience when selecting
      journal articles. Possible implications for collection development are discussed.

PMID- 11837260
TI  - Coping with a MEDLIB-L service outage.
AB  - OBJECTIVE: The study assessed the coping strategies of MEDLIB-L subscribers
      during an unexpected disruption in the list's service. METHODS: An online survey
      of MEDLIB-L subscribers was performed following a six-day service outage in
      August 1999. RESULTS: Respondents' information needs resulted in two distinct
      coping strategies. Subscribers without a recognized information need or an
      information need determined to be not pressing coped by waiting out the
      interruption. Subscribers with pressing information needs turned to alternative
      methods of resolving these needs. CONCLUSIONS: While most respondents missed the
      list and the assistance that it provided, many did not feel that the outage
      required significant coping strategies. The outage was viewed as a "minor
      stressor" and did not require secondary-level assessment of the availability and
      suitability of alternative resources.

PMID- 11837261
TI  - Financing North American medical libraries in the nineteenth century.
AB  - Culture not only justifies the existence of libraries but also determines the
      level of funding libraries receive for development. Cultural appreciation of the
      importance of libraries encourages their funding; lack of such appreciation
      discourages it. Medical library development is driven by culture in general and
      the culture of physicians in particular. Nineteenth-century North American
      medical library funding reflected the impact of physician culture in three
      phases: (1) Before the dawn of anesthesia (1840s) and antisepsis (1860s), when
      the wisdom of elders contained in books was venerated, libraries were well
      supported. (2) In the last third of the nineteenth century, as modern medicine
      grew and as physicians emphasized the practical and the present, rather than
      books, support for medical libraries declined. (3) By the 1890s, this attitude
      had changed because physicians had come to realize that, without both old and new
      medical literature readily available, they could not keep up with rapidly
      changing current clinical practice or research. Thus, "The Medical Library
      Movement" heralded the turn of the century.

PMID- 11837262
TI  - Clinical veterinary librarianship--the Texas A&M University experience.

PMID- 11837263
TI  - The physician-patient relationship in an electronic environment: a regional
      snapshot.

PMID- 11837265
TI  - Public Health Outreach Forum: lessons learned.

PMID- 11837264
TI  - Public Health Outreach Forum: report.

PMID- 11837266
TI  - Preservation.

PMID- 11837267
TI  - Deep brain stimulation in Parkinson's disease.

PMID- 11837268
TI  - Deep brain stimulation in Parkinson's disease.

PMID- 11837269
TI  - B-type natriuretic peptide and acute coronary syndromes.

PMID- 11837270
TI  - Spironolactone and ACE inhibition in chronic renal failure.

PMID- 11837272
TI  - Pharmacy's social movement at the turn of the century: introduction to
      pharmaceutical care symposium.

PMID- 11837271
TI  - George Urdang in Madison: as I remember him.

PMID- 11837273
TI  - The role of pharmacy organizations in transforming the profession: the case of
      pharmaceutical care.

PMID- 11837274
TI  - Predictive pharmacotherapy outcomes: a strategic value proposition for ongoing
      assimilation of pharmaceutical care.

PMID- 11837275
TI  - The salamander as a drug in Nicander's writings.

PMID- 11837277
TI  - The competition for talent.

PMID- 11837276
TI  - Clinical picture: asymmetrical fat embolism.

PMID- 11837279
TI  - Neuroscience of stuttering.

PMID- 11837278
TI  - Bloodthirsty hitchhikers?

PMID- 11837280
TI  - Building coalitions: lessons from the Alliance for a Healthy New England.
AB  - Official pronouncements that the U.S. economy is in recession have confirmed the
      bad news that health care advocates began experiencing months ago. State budgets
      are deep in deficit. Medicaid programs are in jeopardy. And making the case for
      expanded health care access now seems harder than ever. There is good news,
      though: in the Alliance for a Healthy New England, health advocates may have
      found a new funding mechanism. Built on a broad-based coalition model, the
      Alliance is seeking to raise tobacco taxes in all six New England states, with
      the revenue generated to be used for tobacco control and expanded health care
      access. This States of Health looks at how the diverse organizations that make up
      the Alliance are learning to work together--and why working together is so
      valuable.

PMID- 11837281
TI  - Asexual erythrocytic forms of Plasmodium falciparum in asymptomatic American and
      Korean soldiers serving in Vietnam.

PMID- 11837282
TI  - Topical antifungal drug products for over-the-counter human use; amendment of
      final monograph. Final rule.
AB  - The Food and Drug Administration (FDA) is issuing a final rule amending the final
      monograph for over-the-counter (OTC) topical antifungal drug products to add the
      ingredient clotrimazole as generally recognized as safe and effective for the
      treatment of athlete's foot, jock itch, and ringworm. This final rule is part of
      FDA's ongoing review of OTC drug products.

PMID- 11837284
TI  - What does it mean to "review" a protocol? Johns Hopkins & OHRP.

PMID- 11837283
TI  - Open label extension studies and the ethical design of clinical trials.

PMID- 11837285
TI  - Eligibility, extrapolation and equipoise: unlearned lessons in the ethical
      analysis of clinical research.

PMID- 11837286
TI  - Trust in scientific publishing.
AB  - Trust is an important phenomenon to reduce organizational complexity and
      uncertainty. In the literature many types of trust are distinguished. An
      important framework to understand the variety and development of trust in
      organisations is provided by Zucker. She distinguishes three types of trust:
      process-based trust, institutional-based trust, characteristic-based trust. In
      this article we will add a fourth type: values-based trust. Similarly, it is
      customary in scientific communication to distinguish four main communication
      functions: registration, archiving, certification, awareness. These types of
      trust and communication functions offer somewhat similar classification schemes.
      In this paper we will elaborate on these classification schemes with the aim to
      analyse possible similarities or even mapping. Such similarities will allow
      drawing conclusions on the development of trust in a (virtual) organisation in
      general and the process of scientific communication as a special kind of a
      (virtual) organisation in particular.

PMID- 11837287
TI  - Who counts morally?

PMID- 11837288
TI  - Michael Perry, Peter Singer, and Quasimodo: persons with disabilities and the
      nature of rights.

PMID- 11837289
TI  - Using Augustine in contemporary sexual ethics. A response to Gilbert Meilaender.
AB  - In response to Gilbert Meilaender's innovative interpretation of Augustine and of
      Roman Catholic teaching, the author suggests (1) that Meilaender attributes to
      Augustine a more positive view of sexual pleasure than the texts will support,
      (2) that modern Roman Catholic teaching suggests that love should have priority
      over procreation as a meaning of sex; and (3) that the moral logic of
      Meilaender's argument does not require a rejection of all reproductive
      technologies. Nonetheless, the author agrees that a more critical attitude should
      be adopted toward the reasons for which technologically assisted reproduction is
      promoted and undertaken, as well as toward its social impact.

PMID- 11837290
TI  - Paintings by Pancrace Bessa for Herbier General.

PMID- 11837291
TI  - Bacillus endophyticus sp. nov., isolated from the inner tissues of cotton plants
      (Gossypium sp.).
AB  - Four strains of aerobic, endospore-forming bacteria were isolated from the inner
      tissues of healthy cotton plants (Gossypium sp., Dushanbe, Tajikistan). The
      organisms had identical randomly amplified polymorphic DNA patterns that
      distinguished them from other bacilli that are commonly isolated from plant
      tissues, e.g. Bacillus amyloliquefaciens, Bacillus licheniformis, Bacillus
      pumilus and Bacillus subtilis. PCR amplification of 16S-23S rRNA spacer regions
      suggested that the four strains could be assigned to two highly related taxa,
      which correlated with differences in cell morphology. However, the cloned spacer
      region provided a simple and specific hybridization probe for all four strains.
      The virtually complete 16S rDNA sequences were prepared for representatives of
      the two groups (strains 2DT(T) and 12DX) and differed by only two bases, thus
      supporting classification of the four strains in a single taxon at the species
      level. Phylogenetic analyses indicated that strain 2DT(T) belonged to the genus
      Bacillus and was most closely related to Bacillus sporothermodurans DSM 10599T
      with a sequence similarity of 94.8%. It is concluded that the four strains belong
      to a novel species of Bacillus for which the name Bacillus endophyticus sp. nov.
      is proposed. The type strain is 2DT(T) (= UCM B-5715T = CIP 106778T).

PMID- 11837292
TI  - Alicyclobacillus herbarius sp. nov., a novel bacterium containing omega
      cycloheptane fatty acids, isolated from herbal tea.
AB  - A thermo-acidophilic gram-positive bacterium, strain CP-1T, which grows
      aerobically at 35-65 degrees C (optimum 55-60 degrees C) and at pH 3.5-6.0
      (optimum pH 4.5-5.0), was isolated from a herbal tea made from the dried flowers
      of hibiscus. Phylogenetic analysis of the 16S rRNA gene sequences showed that
      this bacterium was clearly distinguishable from previously described species of
      the genera Alicyclobacillus and Sulfobacillus. Strain CP-1T had unique omega
      cycloheptane fatty acids as the major membrane lipid component, a characteristic
      which is peculiar to Alicyclobacillus cycloheptanicus. However, phenotypic and
      chemotaxonomic characteristics of strain CP-1T were different from those of the
      type strain of A. cycloheptanicus. DNA-DNA hybridization between the type strains
      of Alicyclobacillus species and Sulfobacillus disulfidooxidans was <20%,
      indicating that strain CP-1T represents a distinct species. On the basis of these
      results, the name Alicyclobacillus herbarius is proposed for this organism. The
      type strain is strain CP-1T (= DSM 13609T = IAM 14883T = NRIC 0477T).

PMID- 11837293
TI  - Taxonomic characterization of Mogibacterium diversum sp. nov. and Mogibacterium
      neglectum sp. nov., isolated from human oral cavities.
AB  - Novel isolates, strains HM-7, HM-6, HH-31, P9a-hT and UJB13-d, which were
      isolated from tongue plaque and necrotic dental pulp, were studied taxonomically
      and phylogenetically. These organisms were anaerobic, non-spore-forming, gram
      positive, rod-shaped bacteria that were inert in most of the conventional
      biochemical tests and phenotypically resemble Mogibacterium species or
      asaccharolytic Eubacterium species. The G+C contents of the DNAs from the novel
      isolates ranged from 41 to 42 mol %. DNA-DNA hybridization studies demonstrated
      that these strains might be assigned to the genus Mogibacterium but not to the
      previously described species. It was also apparent that strain HM-7 belonged to
      the same species as strains HM-6 and HH-31, and that strains P9a-hT and UJB13-d
      belonged to a second species. The levels of DNA-DNA relatedness to asaccharolytic
      Eubacterium species, including Eubacterium brachy, Eubacterium nodatum,
      Eubacterium saphenum and the more recently proposed Eubacterium minutum and
      Eubacterium exiguum (reclassified as Slackia exigua), are less than 2%. The
      results of 16S rDNA sequence comparisons revealed that these organisms represent
      novel lineages distinct from all previously described species of gram-positive,
      rod-shaped bacteria. On the basis of phenotypic characteristics, DNA-DNA
      hybridization data and phylogenetic analysis with 16S rRNA gene sequence data,
      new species are proposed, namely Mogibacterium diversum (for strains HM-7, HM-6
      and HH-31) and Mogibacterium neglectum (for strains P9a-hT and UJB13-d). HM-7T (=
      ATCC 700923T = JCM 11205T) is the type strain of the former and P9a-hT (= ATCC
      700924T = JCM 11204T) is the type strain for the latter.

PMID- 11837294
TI  - Halomonas alimentaria sp. nov., isolated from jeotgal, a traditional Korean
      fermented seafood.
AB  - A gram-negative, moderately halophilic bacterial strain, YKJ-16T, which was
      isolated from jeotgal, a traditional Korean food, was considered to be a member
      of the genus Halomonas. Cells of strain YKJ-16T are non-motile and cocci or short
      rods, unlike most Halomonas species. However, chemotaxonomic and phylogenetic
      analyses demonstrated that strain YKJ-16T belongs to the genus Halomonas. The
      predominant isoprenoid quinone is ubiquinone-9. The major fatty acids are
      C18.1omega7c, C16:0, C19:0 cyclo omega8c and C16:1omega7c and/or iso C15:0 20H.
      The phylogenetic tree showed that strain YKJ-16T forms a distinct evolutionary
      lineage within the radiation comprising Halomonas species and forms a coherent
      cluster with Halomonas halodenitrificans, Halomonas cupida and Halomonas
      pacifica. Levels of 16S rDNA similarity between strain YKJ-16T and the type
      strains of other Halomonas species are 93.0-96.3%. Levels of DNA-DNA relatedness
      indicate a taxonomic status of strain YKJ-16T as a species different from the
      three species that form the coherent cluster mentioned above. Morphologically,
      strain YKJ-16T is also clearly differentiated from the type strains of H. cupida
      and H. pacifica. Accordingly, on the basis of the phenotypic characteristics, 16S
      rDNA sequence analysis and DNA relatedness data, strain YKJ-16T should be placed
      in the genus Halomonas as a novel species. The name Halomonas alimentaria sp.
      nov. is proposed with strain YKJ-16T (= KCCM 41042T = JCM 10888T) as the type
      strain.

PMID- 11837295
TI  - PAH-degradation by Paenibacillus spp. and description of Paenibacillus
      naphthalenovorans sp. nov., a naphthalene-degrading bacterium from the
      rhizosphere of salt marsh plants.
AB  - Bacteria belonging to the genus Paenibacillus were isolated by enrichment from
      petroleum-hydrocarbon-contaminated sediment and salt marsh rhizosphere using
      either naphthalene or phenanthrene as the sole carbon source, and were
      characterized using phenotypic, morphological and molecular techniques. The
      isolates were grouped by their colony morphologies and polyaromatic hydrocarbon
      degradation patterns. Phenanthrene-degrading isolates produced mottled colonies
      on solid media and were identified as P. validus by fatty acid methyl ester and
      16S rRNA gene sequence analyses. In contrast, the naphthalene-degrading isolates
      with mucoid colony morphology were distantly related to Paenibacillus validus,
      according to fatty acid methyl ester and 16S rRNA gene sequence analyses. The
      predominant fatty acids of the mucoid isolates were 15:0 anteiso, 16:1omega11c,
      16:0 and 17:0 anteiso, constituting, on average, 50.5, 12.0, 11.2 and 6.5% of the
      total, respectively. The G+C contents of their DNA ranged from 47 to 52 mol%. The
      16S rDNA sequence analysis revealed the highest (< or = 94%) similarity to P.
      validus. In addition, phylogenetic analyses based on 16S rDNA sequences showed
      that the mucoid isolates formed a distinct cluster within Paenibacillus. DNA-DNA
      hybridization experiments showed only a 6% DNA similarity between the type strain
      of P. validus and mucoid strain PR-N1. On the basis of the morphological,
      phenotypic and molecular data, the naphthalene-degrading isolates merit
      classification as a new Paenibacillus species, for which the name Paenibacillus
      naphthalenovorans sp. nov. is proposed, with PR-N1T (= ATCC BAA-206T = DSM
      14203T) as the type strain.

PMID- 11837296
TI  - Taxonomic study of Weissella confusa and description of Weissella cibaria sp.
      nov., detected in food and clinical samples.
AB  - A taxonomic study was conducted to clarify the relationships of two bacterial
      populations belonging to the genus Weissella. A total of 39 strains originating
      mainly from Malaysian foods (22 strains) and clinical samples from humans (9
      strains) and animals (6 strains) were analysed using a polyphasic taxonomic
      approach. The methods included classical phenotyping, whole-cell protein
      electrophoresis, 16S and 23S rDNA RFLP (ribotyping), determination of 16S rDNA
      sequence homologies and DNA-DNA reassociation levels. Based on the results, the
      strains were considered to represent two different species, Weissella confusa and
      a novel Weissella species, for which the name Weissella cibaria sp. nov. is
      proposed. Weisella confusa possessed the highest 16S rDNA sequence similarity to
      Weisella cibaria, but the DNA-DNA reassociation experiment showed hybridization
      levels below 49% between the strains studied. The numerical analyses of Weisella
      confusa and Weisella cibaria strains did not reveal any specific clustering with
      respect to the origin of the strains. Based on whole-cell protein
      electrophoresis, and ClaI and HindIII ribotyping patterns, food and clinical
      isolates were randomly located in the two species-specific clusters obtained.

PMID- 11837297
TI  - Halorubrum tebenquichense sp. nov., a novel halophilic archaeon isolated from the
      Atacama Saltern, Chile.
AB  - A novel extremely halophilic archaeon was isolated from Lake Tebenquiche,
      situated in the northern part of the Atacama Saltern, Chile. The cells of these
      micro-organisms were mostly irregularly disc-shaped. They grew in medium
      containing saturated concentrations of NaCl and did not require magnesium for
      optimal growth. The polar lipid composition revealed the presence of mannosyl-2
      sulfate-(1-4)-glycosyl-archaeol, the main glycolipid of the genus Halorubrum, and
      two new glycolipids. The G+C content of the DNA was 63.2 mol%. Phylogenetic
      analysis of the 16S rRNA gene placed strain ALT6-92T within the Halorubrum
      cluster. The low DNA-DNA hybridization value justified classification in a new
      species for which the name Halorubrum tebenquichense sp. nov. is proposed. The
      type strain is ALT6-92T (= CECT 5317T = DSM 14210T).

PMID- 11837298
TI  - Anaerobaculum mobile sp. nov., a novel anaerobic, moderately thermophilic,
      peptide-fermenting bacterium that uses crotonate as an electron acceptor, and
      emended description of the genus Anaerobaculum.
AB  - A novel anaerobic, moderately thermophilic, peptide-fermenting bacterium, strain
      NGA(T), was isolated from an anaerobic wool-scouring wastewater treatment lagoon.
      The cells were gram-negative, straight rods of 0.5-1.0 x 2.0-4.0 microm, motile
      by means of a single flagellum. The DNA G+C content was 51.5 mol%. The optimum pH
      and temperature range for growth were 6.6-7.3 and 55-60 degrees C, respectively.
      The optimum NaCl concentration was 0.08 g l(-1). The bacterium fermented organic
      acids (malate, tartrate, pyruvate, glycerol and fumarate), a few carbohydrates
      (starch, glucose, fructose and gluconate), Casamino acids, tryptone and yeast
      extract. Carbohydrates and organic acids were converted to acetate, hydrogen and
      CO2. The bacterium oxidized leucine to isovalerate with crotonate as an electron
      acceptor, but not in co-culture with Methanothermobacter thermoautotrophicus DSM
      3720T. Thiosulfate, sulfur and cystine were reduced to sulfide and crotonate was
      reduced to butyrate with glucose and tryptone-yeast extract as electron donors.
      Phylogenetic analysis of the 16S rRNA gene indicated that strain NGA(T) was
      related to Anaerobaculum thermoterrenum (98% similarity), the only described
      species of the genus. The DNA-DNA hybridization value for strain NGA(T) and A.
      thermoterrenum ACM 5076T was 40.8%. On the basis of these results, strain NGA(T)
      is proposed as a novel species of the genus Anaerobaculum, namely Anaerobaculum
      mobile sp. nov. The type strain is NGA(T) (= DSM 13181T =ATCC BAA-54T).

PMID- 11837299
TI  - Phylogenetic classification of Bartonella species by comparing groEL sequences.
AB  - Bartonella is a bacterial genus classified in the alpha-Proteobacteria on the
      basis of 165 rDNA sequence comparison. The highly conserved heat-shock chaperonin
      protein, GroEL, has proved to be a valuable resolving tool to classify ten
      Bartonella species. The groEL gene was amplified and sequenced from ten
      Bartonella isolates: Bartonella alsatica, Bartonella vinsonii subsp. arupensis,
      Bartonella taylorii, Bartonella tribocorum, Bartonella birtlesii, Bartonella
      henselae Marseille (URLLY8), B. henselae (90-615), B. henselae (Fizz), B.
      henselae (CAL-1) and B. henselae (SA-2). Then, phylogenetic relationships were
      inferred between our isolates and eight other species and subspecies from the
      comparison of both 16S rDNA and groEL sequences using parsimony, neighbour
      joining and maximum-likelihood methods. By using groEL sequences, the first
      reliable classification of most known Bartonella species and subspecies was
      established. Four strongly supported subgroups were distinguished: firstly, the
      two human pathogens B. henselae and Bartonella quintana; secondly, a cluster
      including four rodent isolates, Bartonella elizabethae, B. tribocorum, Bartonella
      grahamii and B. taylorii; thirdly, a cluster including the B. vinsonii subspecies
      (B. vinsonii subsp. vinsonii, arupensis and berkhoffii); and lastly, B. birtlesii
      and 'Bartonella weissi'. 'Bartonella washoensis', B. alsatica, Bartonella
      doshiae, Bartonella bacilliformis and Bartonella clarridgeiae did not reliably
      cluster with any other Bartonella species. In addition, the groEL gene was shown
      to be useful in subtyping six B. henselae isolates into three variants: Houston,
      Marseille and Fizz.

PMID- 11837300
TI  - Anaerophaga thermohalophila gen. nov., sp. nov., a moderately thermohalophilic,
      strictly anaerobic fermentative bacterium.
AB  - The strictly anaerobic gram-negative bacterium strain Fru22T grows at 50 degrees
      C in media containing up to 75 g NaCl l(-1). Hexoses and pentoses are fermented
      to equal molar amounts of acetate, propionate and succinate, and no CO2 is
      formed. An orange-red pigment similar to flexirrubin is produced during
      stationary phase upon exposure to light for several days. Cells also produce a
      surface-active extracellular compound which lowers the surface tension of the
      medium. This tenside is heat-tolerant up to 70 degrees C and is destroyed by
      treatment with proteinase K or trypsin, but not by lipase. Comparative 16S rDNA
      sequence analysis confirmed a phylogenetic affiliation of strain Fru22T to the
      phylum Bacteroides (Cytophaga/Flavobacterium/Bacteroides), moderately related to
      the genus Marinilabilia. Therefore, on the basis of phylogenetic, phenotypic and
      physiological evidence, a new genus, Anaerophaga, is proposed to harbour strain
      Fru22T (DSM 12881T, OCM 798T) which is described as the type strain of a new
      species, Anaerophaga thermohalophila gen. nov., sp. nov.

PMID- 11837301
TI  - Brackiella oedipodis gen. nov., sp. nov., gram-negative, oxidase-positive rods
      that cause endocarditis of cotton-topped tamarin (Saguinus oedipus).
AB  - A gram-negative, oxidase-positive, rod-shaped bacterium isolated from the heart
      of a cotton-topped tamarin was characterized by 16S rDNA sequence analysis, SDS
      PAGE of whole-cell proteins, fatty acid analysis and biochemical tests. Outer
      membrane proteins, iron-regulated outer-membrane proteins, lipopolysaccharides
      and siderophore production were studied. On the basis of the results, the
      organism belongs to the beta-Proteobacteria where it forms a separate line of
      descent, for which a novel genus and species are proposed, Brackiella oedipodis
      (LMG 19451T = DSM 13743T = NCIMB 13739T). Nearest phylogenetic neighbours of the
      new genus are Taylorella, Pelistega, Bordetella, Alcaligenes and Achromobacter.

PMID- 11837302
TI  - Roseiflexus castenholzii gen. nov., sp. nov., a thermophilic, filamentous,
      photosynthetic bacterium that lacks chlorosomes.
AB  - A novel thermophilic, photosynthetic bacterium, designated strain HLO8T, was
      isolated from a bacterial mat in a Japanese hot spring. Morphologically, the
      isolate was an unbranched multicellular filament with a cell diameter of 0.8-1.0
      microm. The bacterium was red to reddish-brown in colour and formed a distinct
      red bacterial mat in the natural environment. It was able to grow
      photoheterotrophically under anaerobic light conditions and also
      chemoheterotrophically under aerobic dark conditions. Optimal growth occurred at
      50 degrees C and pH 7.5-8.0. The cells contained bacteriochlorophyll (Bchl) a and
      gamma-carotene derivatives as photosynthetic pigments, but lacked Bchl c and
      chlorosomes. Cellular fatty acids in the isolate were mainly C16:0, C14:0 and
      C15:0. The major quinone was menaquinone-11. The DNA G+C content was 62.0 mol%
      (by HPLC). Phylogenetic analysis based on 16S rDNA sequencing suggested that the
      isolate belonged to the anoxygenic filamentous phototrophic bacteria represented
      by Chloroflexus aurantiacus, but was clearly distant from all members in this
      group (the sequence similarities between the isolate and its relatives were less
      than 83.8%). Based on genotypic and phenotypic data, the name Roseiflexus
      castenholzii gen. nov., sp. nov. is proposed for this isolate; the type strain is
      HLO8T (= DSM 13941T = JCM 11240T).

PMID- 11837303
TI  - Shewanella frigidimarina and Shewanella livingstonensis sp. nov. isolated from
      Antarctic coastal areas.
AB  - Three strains of psychrophilic bacteria isolated from Antarctic coastal marine
      environments were studied to determine their taxonomic position. These bacteria
      were gram-negative rods, facultatively anaerobic and motile by means of a single
      polar flagellum. None of the bacterial isolates had an Na+ requirement. Only one
      of the strains was capable of producing H2S from thiosulfate. The DNA base
      content of these bacteria was 41-42 mol % G+C. DNA-DNA hybridization experiments
      showed that the isolates formed two related groups that exhibited about 70 and
      24% DNA-DNA homology, respectively, with the type strain of Shewanella
      frigidimarina. The fatty acid profiles of the bacterial isolates were similar to
      the profiles of other Shewanella species. All the strains contained both
      ubiquinones and menaquinones, like Shewanella species. Methylmenaquinones were
      also found. 16S rRNA gene analysis confirmed that isolated strains belonged to
      the genus Shewanella and were phylogenetically related to the newly identified
      Shewanella frigidimarina. The results of the polyphasic taxonomic study assigned
      the three isolates to Shewanella and two of them specifically to Shewanella
      frigidimarina. The name Shewanella livingstonensis sp. nov. (type strain LMG
      19866T) is proposed for the third organism.

PMID- 11837304
TI  - Isobaculum melis gen. nov., sp. nov., a Carnobacterium-like organism isolated
      from the intestine of a badger.
AB  - Phenotypic and phylogenetic studies were performed on a hitherto undescribed
      facultatively anaerobic, catalase-negative, gram-positive rod-shaped organism,
      strain M577-94T, isolated from the small intestine of a dead badger. It resembled
      carnobacteria in terms of its long-chain cellular fatty acid composition, but
      differed markedly from the latter in possessing a cell-wall murein based on L
      lysine (type L-Lys-L-Thr-Gly). Comparative 16S rRNA gene sequencing showed that
      the unknown bacterium represents a new line closely related to, albeit distinct
      from, the genera Carnobacterium and Desemzia. On the basis of phylogenetic and
      phenotypic evidence, it is proposed that strain M577-94T be classified as
      Isobaculum melis gen. nov., sp. nov. The type strain of Isobaculum melis is CCUG
      37660T (= DSM 13760T).

PMID- 11837305
TI  - Lactobacillus equi sp. nov., a predominant intestinal Lactobacillus species of
      the horse isolated from faeces of healthy horses.
AB  - Lactobacillus equi sp. nov. is described on the basis of 18 strains isolated as
      one of the predominant intestinal lactobacilli from horse faecal specimens. These
      18 strains were isolated from 10 horses of 6 different farms out of 20 horses of
      10 farms examined. They were gram-positive, facultatively anaerobic, catalase
      negative, non-spore-forming, non-motile, lactic-acid-homofermentative rods. The
      DNA G+C content was 38.9+/-0.8 mol %. DNA-DNA hybridization failed to associate
      these strains closely with any of the validly described type strains used.
      Analysis of the 16S rRNA gene sequence of representative strain YIT 0455T
      revealed that the new isolates represent a new Lactobacillus species, for which
      the name Lactobacillus equi is proposed. The type strain is YIT 0455T (= ATCC BAA
      261T = JCM 10991T).

PMID- 11837306
TI  - Desulfovibrio magneticus sp. nov., a novel sulfate-reducing bacterium that
      produces intracellular single-domain-sized magnetite particles.
AB  - A novel type of dissimilatory sulfate-reducing bacterium, designated strain RS
      1T, capable of producing intracellular magnetite particles (magnetosomes) was
      isolated from freshwater sulfide-rich sediments. Phylogenetic analysis based on
      16S rDNA sequences revealed that RS-1T is a member of the genus Desulfovibrio.
      Its closest known relative is Desulfovibrio burkinensis (sequence similarity of
      98.7%). Strain RS-1T contains desulfoviridin, c-type cytochromes and, unlike
      other Desulfovibrio spp., it possesses menaquinone MK-7(H2) instead of MK-6 or MK
      6(H2). Strain RS-1T is also unique compared with other members of Desulfovibrio
      in its ability to synthesize intracellular magnetite particles. A novel species,
      Desulfovibrio magneticus sp. nov., is proposed for RS-1T (= ATCC 700980T = DSM
      13731T), a sulfate-reducing magnetotactic bacterium.

PMID- 11837307
TI  - Pseudoalteromonas issachenkonii sp. nov., a bacterium that degrades the thallus
      of the brown alga Fucus evanescens.
AB  - Eleven non-pigmented strains of gram-negative, aerobic, marine bacteria with
      polar flagella were isolated from the thallus of the brown alga Fucus evanescens
      collected in the Kraternaya Bight of the Kurile Islands in the Pacific Ocean.
      These organisms were conspecific and exhibited high levels of genetic relatedness
      (up to 91%). The G+C contents of the DNAs of these strains were 42.9-43.3 mol%.
      These halophilic bacteria had bacteriolytic, proteolytic and haemolytic
      activities and degraded algal polysaccharides, synthesizing a number of glycoside
      hydrolases (fucoidanases, laminaranases, alginases, agarases, pullulanases, beta
      glucosidases, beta-galactosidases, beta-N-acetylglucosaminidases and beta
      xylosidases). By 16S rDNA analysis, the bacteria were shown to belong to the
      genus Pseudoalteromonas, a member of the gamma-subclass of the Proteobacteria.
      DNA from the strains isolated from the brown alga showed 27-54% genetic
      relatedness with respect to DNAs of other type strains of the genus
      Pseudoalteromonas. The phenotypic characteristics, together with the genetic
      evidence, indicate that this group of epiphytic bacteria represents a distinct
      species, Pseudoalteromonas issachenkonii sp. nov., for which the type strain is
      KMM 3549T (= LMG 19697T = CIP 106858T).

PMID- 11837308
TI  - Pseudoalteromonas ruthenica sp. nov., isolated from marine invertebrates.
AB  - On the basis of phenotypic and genotypic characteristics and analysis of 165 rRNA
      sequences, a novel species belonging to the genus Pseudoalteromonas is described.
      Two pale-orange-pigmented strains, KMM 300T and KMM 290, isolated respectively
      from a mussel, Crenomytilus grayanus, and a scallop, Patinopecten yessoensis, are
      marine, gram-negative, aerobic, rod-shaped bacteria that produce a number of
      antimicrobial compounds. The strains are able to degrade gelatin, elastin,
      starch, DNA and Tween 80. Chitin and agar are not degraded. The isolates from
      marine invertebrates grew at NaCl concentrations of 1-9% and a temperature range
      of 10-35 degrees C and did not utilize most of the wide range of carbohydrates
      tested, with the exception of D-glucose, cellobiose and sucrose. The DNA G+C
      content was 48.4-48.9 mol%. The level of DNA homology of the two strains was 98%.
      DNA from the strains isolated from marine invertebrates showed 5-15% genetic
      relatedness to the DNA of other type strains of the genus Pseudoalteromonas. 16S
      rRNA analysis indicated a clear affiliation of the novel bacteria to other
      species of the genus. The strains are assigned to a novel species, Pseudomonas
      ruthenica sp. nov., with the type strain KMM 300T (= LMG 19699T = CIP 106857T).

PMID- 11837309
TI  - Phylogeny of the family Halomonadaceae based on 23S and 165 rDNA sequence
      analyses.
AB  - In this study, we have evaluated the phylogenetic status of the family
      Halomonadaceae, which consists of the genera Halomonas, Chromohalobacter and
      Zymobacter, by comparative 23S and 16S rDNA analyses. The genus Halomonas
      illustrates very well a situation that occurs often in bacterial taxonomy. The
      use of phylogenetic tools has permitted the grouping of several genera and
      species believed to be unrelated according to conventional taxonomic techniques.
      In addition, the number of species of the genus Halomonas has increased as a
      consequence of new descriptions, particularly during the last few years, but
      their features are too heterogeneous to justify their placement in the same genus
      and, therefore, a re-evaluation seems necessary. We have determined the complete
      sequences (about 2900 bases) of the 23S rDNA of 18 species of the genera
      Halomonas and Chromohalobacter and resequenced the complete 16S rDNA sequences of
      seven species of Halomonas. The results of our analysis show that two
      phylogenetic groups (respectively containing five and seven species) can be
      distinguished within the genus Halomonas. Six other species cannot be assigned to
      either of the above-mentioned groups. Furthermore, Halomonas marina forms a
      separate branch at a deeper level than the other species of the genus Halomonas,
      which suggests that it should be ascribed to a separate genus. The genus
      Chromohalobacter forms a monophyletic group constituted by Chromohalobacter
      marismortui, the recently reclassified species Chromohalobacter canadensis and
      Chromohalobacter israelensis and the recently proposed species Chromohalobacter
      salexigens. Finally, we propose to include the genus Carnimonas, with its single
      species Carnimonas nigrificans, in the family Halomonadaceae.

PMID- 11837310
TI  - Methylocapsa acidiphila gen. nov., sp. nov., a novel methane-oxidizing and
      dinitrogen-fixing acidophilic bacterium from Sphagnum bog.
AB  - A novel genus and species, Methylocapsa acidiphila gen. nov., sp. nov., are
      proposed for a methane-oxidizing bacterium isolated from an acidic Sphagnum peat
      bog. This bacterium, designated strain B2T, represents aerobic, gram-negative,
      colourless, non-motile, curved coccoids that form conglomerates covered by an
      extracellular polysaccharide matrix. The cells use methane and methanol as sole
      sources of carbon and energy and utilize the serine pathway for carbon
      assimilation. Strain B2T is a moderately acidophilic organism with growth between
      pH 4.2 and 7.2 and at temperatures from 10 to 30 degrees C. The cells possess a
      well-developed system of intracytoplasmic membranes (ICM) packed in parallel on
      only one side of the cell membrane. This type of ICM structure represents a novel
      arrangement, which was termed type III. The resting cells are Azotobacter-type
      cysts. Strain B2T is capable of atmospheric nitrogen fixation; it possesses
      particulate methane monooxygenase and does not express soluble methane
      monooxygenase. The major phospholipid fatty acid is 18:1omega7c and the major
      phospholipids are phosphatidylglycerols. The G+C content of the DNA is 63.1 mol%.
      This bacterium belongs to the alpha-subclass of the Proteobacteria and is most
      closely related to the acidophilic methanotroph Methylocella palustris KT (97.3%
      16S rDNA sequence similarity). However, the DNA-DNA hybridization value between
      strain B2T and Methylocella palustris K(T) is only 7%. Thus, strain B2T is
      proposed to comprise a novel genus and species, Methylocapsa acidiphila gen.
      nov., sp. nov. Strain B2T (= DSM 13967T = NCIMB 13765T) is the type strain.

PMID- 11837311
TI  - Pseudoalteromonas maricaloris sp. nov., isolated from an Australian sponge, and
      reclassification of [Pseudoalteromonas aurantia] NCIMB 2033 as Pseudoalteromonas
      flavipulchra sp. nov.
AB  - A marine, gram-negative, aerobic bacterium that produced cytotoxic, lemon-yellow,
      chromopeptide pigments that inhibited the development of sea urchin eggs has been
      isolated from the Australian sponge Fascaplysinopsis reticulata Hentschel. The
      cells of the organism were rod-shaped with a single polar flagellum and they
      required NaCl for growth (0.5-10%) with optimum growth at 1-3% NaCl. The
      temperature for growth was 10-37 degrees C, with optimum growth at 25-30 degrees
      C. Growth occurred at pH values from 6.0 to 10.0, with optimum growth at pH 6.0
      8.0. Major phospholipids were phosphatidylethanolamine, phosphatidylglycerol and
      lyso-phosphatidylethanolamine. Of 26 fatty acids with 11-19 carbon atoms that
      were detected, 16:1omega7, 16:0, 17:1omega8 and 18:1omega7 were predominant. The
      DNA G+C content was 38.9 mol%. All of these phenotypic and chemotaxonomic
      characters place the organism in the genus Pseudoalteromonas (Gauthier et al,
      1995). These data are consistent with the phylogenetic analyses that confirmed
      that strain KMM 636T is a member of the Pseudoalteromonas cluster in the gamma
      subclass of the Proteobacteria. DNA-DNA hybridization experiments revealed that
      the levels of relatedness between the DNA of the strain studied and DNAs of type
      strains of the species that clustered together (on the basis of 16S rDNA
      sequences) and [Pseudoalteromonas aurantia] NCIMB 2033 ranged from 19 to 35%, and
      that the DNA-DNA homology between [P. aurantia] NCIMB 2033 and other
      phylogenetically and/or phenotypically similar type strains ranged from 32 to
      52%. According to the polyphasic evidence presented in this study, it is proposed
      that strain KMM 636T (= LMG 19692T = CIP 106859T) be classified as
      Pseudoalteromonas maricaloris sp. nov. and [P. aurantia] NCIMB 2033 be
      reclassified as Pseudoalteromonas flavipulchra NCIMB 2033T (= KMM 3630T = LMG
      20361T) sp. nov.

PMID- 11837312
TI  - Phylogenetic analysis identifies the invertebrate pathogen Helicosporidium sp. as
      a green alga (Chlorophyta).
AB  - Historically, the invertebrate pathogens of the genus Helicosporidium were
      considered to be either protozoa or fungi, but the taxonomic position of this
      group has not been considered since 1931. Recently, a Helicosporidium sp.,
      isolated from the blackfly Simulium jonesi Stone & Snoddy (Diptera: Simuliidae),
      has been amplified in the heterologous host Helicoverpa zea. Genomic DNA has been
      extracted from gradient-purified cysts. The 185, 28S and 5.8S regions of the
      Helicosporidium rDNA, as well as partial sequences of the actin and beta-tubulin
      genes, were amplified by PCR and sequenced. Comparative analysis of these
      nucleotide sequences was performed using neighbour-joining and maximum-parsimony
      methods. All inferred phylogenetic trees placed Helicosporidium sp. among the
      green algae (Chlorophyta), and this association was supported by bootstrap and
      parsimony jackknife values. Phylogenetic analysis focused on the green algae
      depicted Helicosporidium sp. as a close relative of Prototheca wickerhamii and
      Prototheca zopfii (Chlorophyta, Trebouxiophyceae), two achlorophylous, pathogenic
      green algae. On the basis of this phylogenetic analysis, Helicosporidium sp. is
      clearly neither a protist nor a fungus, but appears to be the first described
      algal invertebrate pathogen. These conclusions lead us to propose the transfer of
      the genus Helicosporidium to Chlorophyta, Trebouxiophyceae.

PMID- 11837313
TI  - Kockovaella barringtoniae sp. nov., a new basidiomycetous yeast species isolated
      from a plant leaf collected in a tropical rain forest in Thailand.
AB  - One yeast strain characterized by the proliferation of non-ballistosporous
      stalked conidia, budding cells and ballistoconidia, the presence of xylose in
      whole-cell hydrolysates, the presence of Q-10 as the major ubiquinone
      isoprenologue, the inability to ferment sugars and positive diazonium blue B
      (DBB) and urease reactions was isolated from a plant sample collected in a
      tropical rain forest in Thailand. The isolate clustered with Kockovaella species
      in the 18S rDNA-based tree. On the basis of the morphological, biochemical and
      molecular phylogenetic characteristics, the isolate was assigned to the genus
      Kockovaella. DNA complementarity experiments showed that the isolate was
      genetically distinct from known species of the genus Kockovaella. The isolate is
      described as Kockovaella barringtoniae sp. nov. The type strain is strain TY-278T
      (= JCM 10998T = TISTR 5770T).

PMID- 11837314
TI  - The status of the species Lactobacillus casei (Orla-Jensen 1916) Hansen and
      Lessel 1971 and Lactobacillus paracasei Collins et al. 1989. Request for an
      opinion.
AB  - On the basis of considerable published evidence, it is concluded that the species
      Lactobacillus casei is not correctly represented by the strain actually
      designated as the type strain ATCC 393. It is proposed that the Judicial
      Commission consider: (1) that ATCC 393T is scientifically unsuitable as the type
      strain of Lactobacillus casei and should be reclassified as Lactobacillus zeae;
      (2) that Lactobacillus casei ATCC 334 and Lactobacillus paracasei strains are
      members of the same taxon and therefore can be united within the name
      Lactobacillus casei (Rules 42 and 23a), the name Lactobacillus paracasei being
      rejected; and (3) designating ATCC 334 as the neotype strain for the species

PMID- 11837315
TI  - International Committee on Systematics of Prokaryotes. Subcommittee on the
      taxonomy of Halobacteriaceae.

PMID- 11837316
TI  - Validation list no. 84. Validation of publication of new names and new
      combinations previously effectively published outside the IJSEM.

PMID- 11837317
TI  - Notification list. Notification that new names and new combinations have appeared
      in volume 51, part 6, of the IJSEM.

PMID- 11837318
TI  - The neomuran origin of archaebacteria, the negibacterial root of the universal
      tree and bacterial megaclassification.
AB  - Prokaryotes constitute a single kingdom, Bacteria, here divided into two new
      subkingdoms: Negibacteria, with a cell envelope of two distinct genetic
      membranes, and Unibacteria, comprising the new phyla Archaebacteria and
      Posibacteria, with only one. Other new bacterial taxa are established in a
      revised higher-level classification that recognizes only eight phyla and 29
      classes. Morphological, palaeontological and molecular data are integrated into a
      unified picture of large-scale bacterial cell evolution despite occasional
      lateral gene transfers. Archaebacteria and eukaryotes comprise the clade neomura,
      with many common characters, notably obligately co-translational secretion of N
      linked glycoproteins, signal recognition particle with 7S RNA and translation
      arrest domain, protein-spliced tRNA introns, eight-subunit chaperonin, prefoldin,
      core histones, small nucleolar ribonucleoproteins (snoRNPs), exosomes and similar
      replication, repair, transcription and translation machinery. Eubacteria
      (posibacteria and negibacteria) are paraphyletic, neomura having arisen from
      Posibacteria within the new subphylum Actinobacteria (possibly from the new class
      Arabobacteria, from which eukaryotic cholesterol biosynthesis probably came).
      Replacement of eubacterial peptidoglycan by glycoproteins and adaptation to
      thermophily are the keys to neomuran origins. All 19 common neomuran character
      suites probably arose essentially simultaneously during the radical modification
      of an actinobacterium. At least 11 were arguably adaptations to thermophily. Most
      unique archaebacterial characters (prenyl ether lipids; flagellar shaft of
      glycoprotein, not flagellin; DNA-binding protein lob; specially modified tRNA;
      absence of Hsp90) were subsequent secondary adaptations to hyperthermophily
      and/or hyperacidity. The insertional origin of protein-spliced tRNA introns and
      an insertion in proton-pumping ATPase also support the origin of neomura from
      eubacteria. Molecular co-evolution between histones and DNA-handling proteins,
      and in novel protein initiation and secretion machineries, caused quantum
      evolutionary shifts in their properties in stem neomura. Proteasomes probably
      arose in the immediate common ancestor of neomura and Actinobacteria. Major gene
      losses (e.g. peptidoglycan synthesis, hsp90, secA) and genomic reduction were
      central to the origin of archaebacteria. Ancestral archaebacteria were probably
      heterotrophic, anaerobic, sulphur-dependent hyperthermoacidophiles;
      methanogenesis and halophily are secondarily derived. Multiple lateral gene
      transfers from eubacteria helped secondary archaebacterial adaptations to
      mesophily and genome re-expansion. The origin from a drastically altered
      actinobacterium of neomura, and the immediately subsequent simultaneous origins
      of archaebacteria and eukaryotes, are the most extreme and important cases of
      quantum evolution since cells began. All three strikingly exemplify De Beer's
      principle of mosaic evolution: the fact that, during major evolutionary
      transformations, some organismal characters are highly innovative and change
      remarkably swiftly, whereas others are largely static, remaining conservatively
      ancestral in nature. This phenotypic mosaicism creates character distributions
      among taxa that are puzzling to those mistakenly expecting uniform evolutionary
      rates among characters and lineages. The mixture of novel (neomuran or
      archaebacterial) and ancestral eubacteria-like characters in archaebacteria
      primarily reflects such vertical mosaic evolution, not chimaeric evolution by
      lateral gene transfer. No symbiogenesis occurred. Quantum evolution of the basic
      neomuran characters, and between sister paralogues in gene duplication trees,
      makes many sequence trees exaggerate greatly the apparent age of archaebacteria.
      Fossil evidence is compelling for the extreme antiquity of eubacteria [over 3500
      million years (My)] but, like their eukaryote sisters, archaebacteria probably
      arose only 850 My ago. Negibacteria are the most ancient, radiating rapidly into
      six phyla. Evidence from molecular sequences, ultrastructure, evolution of
      photosynthesis, envelope structure and chemistry and motility mechanisms fits the
      view that the cenancestral cell was a photosynthetic negibacterium, specifically
      an anaerobic green non-sulphur bacterium, and that the universal tree is rooted
      at the divergence between sulphur and non-sulphur green bacteria. The
      negibacterial outer membrane was lost once only in the history of life, when
      Posibacteria arose about 2800 My ago after their ancestors diverged from
      Cyanobacteria.

PMID- 11837319
TI  - Knoellia sinensis gen. nov., sp. nov. and Knoellia subterranea sp. nov., two
      novel actinobacteria isolated from a cave.
AB  - Two novel strains of the class Actinobacteria were isolated from a cave in China.
      Cells of both strains were gram-positive, non-motile, non-spore-forming and not
      acid-fast and exhibited a rod/coccus growth cycle. Both isolates grew well on
      complex organic media under aerobic conditions. Their cell wall peptidoglycan
      contained meso-diaminopimelic acid as diagnostic diamino acid. The acyl type of
      the glycan chain of peptidoglycan was acetyl. The major respiratory quinone was
      MK-8(H4). The cellular fatty acid profile was characterized by the predominance
      of 13-methyltetradecanoic (i-C15:0), 15-methylhexadecanoic (i-C17:0), 14
      methylpentadecanoic (i-C16:0) and 14-methylhexadecanoic (ai-C17:0) acids. The
      major polar lipids were phosphatidylethanolamine, phosphatidylinositol and
      diphosphatidylglycerol. Mycolic acids were absent. The DNA G+C composition was 68
      69 mol%. 16S rDNA-based phylogenetic analysis revealed an intermediate
      phylogenetic position of the cave isolates between the genera Janibacter and
      Tetrasphaera, which did not permit their unambiguous affiliation to either genus.
      Differences in morphological, physiological and chemotaxonomic properties between
      the two isolates and their closest phylogenetic neighbours support the proposal
      of a new genus and two novel species, Knoellia sinensis gen. nov., sp. nov. and
      Knoellia subterranea sp. nov. The type and only strains of the species are
      respectively HKI 0119T (= DSM 12331T = CIP 106775T) and HKI 0120T (= DSM 12332T =
      CIP 106776T).

PMID- 11837320
TI  - Dietzia psychralcaliphila sp. nov., a novel, facultatively psychrophilic
      alkaliphile that grows on hydrocarbons.
AB  - A novel, facultatively psychrophilic alkaliphile that grows on a chemically
      defined medium containing n-alkanes as the sole carbon source was isolated from a
      drain of a fish product-processing plant. The isolate was an aerobic, non-motile,
      gram-positive bacterium. The bacterium was catalase-positive and oxidase
      negative. The cell wall contained meso-diaminopimelic acid, arabinose and
      galactose; the glycan moiety of the cell wall contained acetyl residues. The G+C
      content of the DNA was 69.6 mol %. Phylogenetic analysis based on 16S rRNA gene
      sequences showed that the isolate was closely related to members of the genus
      Dietzia (96.1-96.8% similarity). Comparisons of phenotypic and chemotaxonomic
      characteristics between the isolate and the two known Dietzia species showed that
      they were very similar. However, the isolate differed from the two known Dietzia
      species in growth temperature range and certain physiological characteristics.
      DNA-DNA hybridization revealed that the isolate had 38.4 and 49.7% relatedness,
      respectively, to Dietzia maris and Dietzia natronolimnaea. On the basis of the
      physiological and biochemical characteristics, the phylogenetic position as
      determined by 16S rRNA gene analysis and DNA-DNA relatedness, it is concluded
      that the isolate should be designated as a novel species, for which the name
      Dietzia psychralcaliphila sp. nov. is proposed. The type strain is ILA-1T (= JCM
      10987T = IAM14896T = NCIMB 13777T).

PMID- 11837321
TI  - Identification of coryneform bacteria and related taxa by Fourier-transform
      infrared (FT-IR) spectroscopy.
AB  - An extensive Fourier-transform infrared (FT-IR) spectroscopy database for the
      identification of bacteria from the two suborders Micrococcineae and
      Corynebacterineae (Actinomycetales, Actinobacteria) as well as other
      morphologically similar genera was established. The database consists of averaged
      IR spectra from 730 reference strains, covering 220 different species out of 46
      genera. A total of 192 species are represented by type strains. The identity of
      352 reference strains was determined by comparative 16S rDNA sequence analysis
      and, if necessary, strains were reclassified accordingly. FT-IR frequency ranges,
      weights and reproducibility levels were optimized for this section of high-G+C
      gram-positive bacteria. In an internal validation, 98.1% of 208 strains were
      correctly identified at the species level. A simulated external validation which
      was carried out using 544 strains from 54 species out of 16 genera resulted in a
      correct identification of 87.3% at the species level and 95.4% at the genus
      level. The performance of this identification system is well within the range of
      those having been reported in the literature for the identification of coryneform
      bacteria by phenotypical methods. Coryneform and related taxa display a certain
      degree of overlapping distribution of different taxonomical markers, leading to a
      limited differentiation capacity of non-genotypical identification methods in
      general. However, easy handling, rapid identification within 25 h starting from a
      single colony, a satisfactory differentiation capacity and low cost, render FT-IR
      technology clearly superior over other routine methods for the identification of
      coryneform bacteria and related taxa.

PMID- 11837322
TI  - A new model using liposomes that allow to distinguish between absorption and
      oxidative properties of sunscreens.
AB  - We have developed a new model using liposome-encapsulated fluorescent probes,
      aiming at assessing both the physical and the biological protection provided by
      filter molecules such as those incorporated in sunscreens. The fluorescent
      indicator Indo-1 or 2',7'-dichlorofluorescin (DCFH) was inside the liposomes, in
      the aqueous inner compartment, whereas the filter molecules octyl
      methoxycinnamate (OMC), benzophenone-3 (BP3) or avobenzone, widely used in
      sunscreens, were incorporated into liposome membranes. When liposome suspensions
      were placed in a fluorometer cuvette exposed to an incident UV beam, the decrease
      of Indo-1 fluorescence as a function of filter concentration was related to the
      extinction coefficient of the filters. On the other hand, when liposome
      suspensions were exposed to moderate UVB doses allowing Indo-1 photobleaching,
      the remaining intact Indo-1 was linked to the protection provided by filter
      containing liposome membranes. Finally, when liposome-encapsulated DCFH was
      exposed to UVB, the degree of photo-oxidation of the fluorescent probe into 2',7'
      dichlorofluorescein accounted for the photoprotection provided by the filter
      contained in liposome membranes. BP3 was more potent and slightly less efficient
      than the other two filters in preventing Indo-1 fluorescence; all three filters
      provided a similar concentration-dependent protection of Indo-1 photobleaching,
      whereas only OMC was able to prevent the photooxidation of DCFH. The liposome
      model presented here has the advantage of combining both physical and biological
      parameters to assess the photoprotection provided by filter molecules, and the
      lack of photoprotection by two sunscreen molecules having a good filter capacity
      highlights the need for such a biological parameter when talking about the safety
      of sunscreens.

PMID- 11837323
TI  - Excited-state properties and in vitro phototoxicity studies of three
      phenothiazine derivatives.
AB  - This work concerns a combined photophysical, photochemical and photobiological
      study of three drugs (psychotherapeutic agents) of the phenothiazine series:
      perphenazine, fluphenazine hydrochloride and thioridazine hydrochloride. The
      excited-state properties were first investigated by stationary and time-resolved
      fluorimetry and by laser flash photolysis. The spectral description was assisted
      by quantum-mechanical calculations with the INDO/1-CI method. In organic media
      the lowest excited singlet state was found to decay by fluorescence (small
      quantum yield) and mainly by intersystem crossing to the lowest triplet state,
      which is responsible for oxygen photosensitization (high yields of singlet oxygen
      production) and photodegradation. A further decay pathway in aqueous solutions
      was the photoionization process, which led to the formation of the phenothiazine
      radical cations and the solvated electron. After the preliminary study of the
      photobehavior in organic solvents and in water, the phototoxicity of the three
      drugs was investigated on various biological substrates through a series of in
      vitro assays under UVA irradiation. Photohemolysis of mouse erythrocytes and
      phototoxicity on cultured murine fibroblasts were observed for all three
      compounds. Lipid photoperoxidation was then investigated using linoleic acid as
      the unsaturated lipid model and isolated red blood cell membranes. The drug
      induced photodamage was also evaluated on proteins by measuring the
      photosensitizing cross-linking in erythrocyte ghosts. The combined approach
      proved to be useful in understanding the mechanism by which these phenothiazine
      derivatives induce skin photosensitization. In particular, the photophysical
      properties of the compounds under investigation and the results of the study on
      their phototoxicity are in agreement with a mechanism that involves the radical
      cation of the drugs as a main intermediate.

PMID- 11837324
TI  - Two bioluminescent diptera: the North American Orfelia fultoni and the Australian
      Arachnocampa flava. Similar niche, different bioluminescence systems.
AB  - Orfelia fultoni is the only bioluminescent dipteran (Mycetophilidae) found in
      North America. Its larvae live on stream banks in the Appalachian Mountains. Like
      their Australasian relative Arachnocampa spp., they build sticky webs to which
      their bioluminescence attracts flying prey. They bear two translucent lanterns at
      the extremities of the body, histologically distinct from the single caudal
      lantern of Arachnocampa spp., and emit the bluest bioluminescence recorded for
      luminescent insects (lambda(max) = 460 nm versus 484 nm from Arachnocampa). A
      preliminary characterization of these two bioluminescent systems indicates that
      they are markedly different. In Orfelia a luciferin-luciferase reaction was
      demonstrated by mixing a hot extract prepared with dithiothreitol (DTT) under
      argon with a crude cold extract. Bioluminescence is not activated by adenosine
      triphosphate (ATP) but is strongly stimulated by DTT and ascorbic acid. Using gel
      filtration, we isolated a luciferase fraction of approximately 140 kDa and an
      additional high molecular weight fraction (possibly a luciferin-binding protein)
      that activated bioluminescence in the presence of luciferase and DTT. The
      Arachnocampa luciferin-luciferase system involves a 36 kDa luciferase and a
      luciferin soluble in ethyl acetate under acidic conditions; the bioluminescence
      is activated by ATP but not by DTT. The present findings indicate that the
      bioluminescence of O. fultoni constitutes a novel bioluminescent system unrelated
      to that of Arachnocampa.

PMID- 11837325
TI  - Intracellular photobleaching of 5,10,15,20-tetrakis(m-hydroxyphenyl) chlorin
      (Foscan) exhibits a complex dependence on oxygen level and fluence rate.
AB  - The understanding of photosensitizer photobleaching is important not only for
      mechanistic studies, but also for the development of monitoring techniques for
      clinical dosimetry in photodynamic therapy. In this study, we investigated the
      intracellular photobleaching of 5,10,15,20-tetrakis(m-hydroxyphenyl)chlorin
      (mTHPC, Foscan) in the murine macrophage cell line J774A.1, using quantitative
      fluorescence imaging microscopy, microspectrofluorometry and
      microspectrophotometry. Using 652 nm laser irradiation, it was found that mTHPC
      exhibits oxygen- and fluence rate-dependent intracellular photobleaching. The
      kinetics showed an inverse dose-rate behavior, i.e. a reduction of fluence rate
      resulted in more photobleaching at comparable fluences. The effect of
      deoxygenation was found to be more complex, with decreased bleaching at low
      fluence rates and increased bleaching at higher fluence rates. The intracellular
      formation of reactive oxygen species was measured using 2',7'
      dichlorodihydrofluorescein diacetate. The results are analyzed in terms of
      competitive Type-I and Type-II mechanisms.

PMID- 11837326
TI  - Involvement of oxidative stress in NF-kappaB activation in endothelial cells
      treated by photodynamic therapy.
AB  - In human endothelial cells ECV 304 and HMEC-1 photosensitized by pyropheophorbide
      a methylester (PPME) in sublethal conditions transcription factor Nuclear Factor
      kappa B (NF-kappaB) activation takes place for several hours. Activated NF-kappaB
      was functional because it stimulated the transcriptional activation of either a
      transfected reporter gene or the endogenous gene encoding interleukin (IL)-8.
      Concomitant with NF-kappaB activation, inhibitor of NF-kappaB alpha (IkappaB
      alpha) was degraded during photosensitization and IkappaB beta, p100, p105 and
      IkappaB epsilon were slightly modified. Reactive oxygen species (ROS) were shown
      to be crucial intermediates in the activation because antioxidants strongly
      decreased NF-kappaB activation. Using both a fluorescent probe and isotope
      substitution, it was shown that ROS, and especially singlet oxygen (1O2), were
      important in the activation process. Because NF-kappaB activation in the presence
      of ROS was suspected to proceed through a pathway independent of the IkappaB
      kinases (IKK), we demonstrated that the IKK were indeed not activated by
      photosensitization but required an intact tyrosine residue at position 42 on
      IkappaB alpha, suggesting the involvement of a tyrosine kinase in the activation
      process. This was further reinforced by the demonstration that herbimycin A, a
      tyrosine kinase inhibitor, prevented NF-kappaB activation by photosensitization
      but not by TNF alpha, a cytokine known to activate NF-kappaB through an IKK
      dependent mechanism.

PMID- 11837327
TI  - Rapid control of wound infections by targeted photodynamic therapy monitored by
      in vivo bioluminescence imaging.
AB  - The worldwide rise in antibiotic resistance necessitates the development of novel
      antimicrobial strategies. In this study we report on the first use of a
      photochemical approach to destroy bacteria infecting a wound in an animal model.
      Following topical application, a targeted polycationic photosensitizer conjugate
      between poly-L-lysine and chlorin(e6) penetrated the gram (-) outer bacterial
      membrane, and subsequent activation with 660 nm laser light rapidly killed
      Escherichia coli infecting excisional wounds in mice. To facilitate real-time
      monitoring of infection, we used bacteria that expressed the lux operon from
      Photorhabdus luminescens; these cells emitted a bioluminescent signal that
      allowed the infection to be rapidly quantified, using a low-light imaging system.
      There was a light-dose dependent loss of luminescence in the wound treated with
      conjugate and light, not seen in untreated wounds. Treated wounds healed as well
      as control wounds, showing that the photodynamic treatment did not damage the
      host tissue. Our study points to the possible use of this methodology in the
      rapid control of wounds and other localized infections.

PMID- 11837329
TI  - UVB-activated psoralen reduces luminal narrowing after balloon dilation because
      of inhibition of constrictive remodeling.
AB  - In this study we have explored the potential of PUVB (8-MOP + UVB) therapy for
      the reduction of luminal narrowing after arterial injury. In 15 rabbits, balloon
      dilation of iliac arteries was performed. In 20 arteries, dilation was combined
      with the delivery of pulsed ultraviolet light B (UVB) irradiation with 10
      arteries being previously subjected to sensitizer infusion. Changes in vessel
      diameter, proliferation and extracellular matrix protein content at 6 weeks were
      evaluated by means of angiography and histomorphometry-immunohistochemistry. We
      found that PUVB, applied at the time of dilation, induced reduction in late loss
      (LL) at 6 weeks (percutaneous transluminal angioplasty vs UVB vs PUVB: 0.64 +/-
      0.15 mm vs 0.61 +/- 0.05 mm vs 0.29 +/- 0.05 mm; p = 0.018). The same holds true
      for constrictive remodeling (0.53 +/- 0.15 mm vs 0.45 +/- 0.06 mm vs 0.15 +/-
      0.05 mm; p = 0.016). In the irradiation groups, LL was independent of acute gain
      (AG), as opposed to the control. Collagen content increased significantly after
      PUVB in media and adventitia, without increased cellular proliferation in all
      vessel layers. Thus, PUVB at the time of dilation reduced luminal narrowing at
      follow-up without effecting proliferation. This effect was independent of AG and
      was associated with increased collagen content in media and adventitia.

PMID- 11837328
TI  - Stage-specific alterations of cyclin expression during UVB-induced murine skin
      tumor development.
AB  - We have evaluated the in vivo correlation between the expression of cell cycle
      markers and skin tumor development in SKH-1 hairless mice in a complete
      photocarcinogenesis protocol. Irradiated mice developed an average of 16 tumors
      per animal by week 23 with the average number of carcinomas per mouse being 2.1.
      The expression of p53 and cyclins A and D1 was confined initially to sporadic
      single cells and gradually developed into foci of patchy intense staining in the
      basal and granular layers of UVB-exposed epidermis. p53 was expressed in all the
      papilloma sections examined, whereas cyclins D1 and A were expressed in 68 and
      71% of these lesions, respectively. In UVB-induced squamous cell carcinomas
      (SCC), p53 was expressed in >90% of the tumors, whereas cyclin D1 was detected in
      55% of the lesions, and cyclin A staining was limited to 27%. These
      immunohistochemical observations were confirmed by Western blotting and protein
      kinase assays. We observed an early wave of cyclin A overexpression and cyclin A
      protein kinase activity preceding the appearance of detectable tumors. Cyclin D1
      and p53 overexpression were coupled with the development of tumors, and these
      changes are likely to be relevant to the pathogenesis of these lesions.

PMID- 11837330
TI  - A rhodopsin-like protein in the plasma membrane of Silvetia compressa eggs.
AB  - Unidirectional blue light directs the rhizoid-thallus axis in the apolar zygote
      of the brown alga, Silvetia compressa. This effect is mediated by an increase in
      the intracellular concentration of guanosine 3', 5'-cyclic monophosphate. In this
      study we show the identification of a rhodopsin-like protein, by means of
      antibody reaction, in the plasma membrane of Silvetia eggs. This new result
      suggests a role for opsins in Silvetia photopolarity.

PMID- 11837332
TI  - End-of-life care focus critical to a complete medical education.

PMID- 11837334
TI  - Travel road that includes complementary and alternative modes of therapy.

PMID- 11837335
TI  - Must question cause of sports-related injuries.

PMID- 11837336
TI  - An alert regarding Canada's financial aid for an osteopathic medical education.

PMID- 11837337
TI  - Patient satisfaction and clinical outcomes associated with osteopathic
      manipulative treatment.
AB  - A patient survey was used to measure and explain patient satisfaction and
      clinical outcomes associated with osteopathic manipulative treatment (OMT).
      Participating in the survey were 459 people who attended an ambulatory OMT
      specialty clinic from March 1998 through September 1998 and who had received OMT
      there at least twice previously. Standardized patient satisfaction scores were
      greatest for overall performance (0.61 +/- 0.29) and interpersonal manner (0.61
      +/- 0.24). Satisfaction with finances (0.11 +/- 0.31) was significantly lower
      than for all other global dimensions of care (P < .001). Subjects perceived OMT
      to be highly efficacious (0.74 +/- 0.34) and reported significant relief from
      pain or discomfort (P < .001) and improvement in mobility (P < .001). Of all the
      respondents, 8.6% attributed an adverse reaction to OMT. Perception of OMT
      efficacy was significantly associated with all dimensions of patient satisfaction
      (P values ranged from less than .001 to .003). Relief from pain or discomfort was
      significantly associated with overall satisfaction (P < .001). Females had
      greater reduction in pain or discomfort than males (P = .001). Respondents
      perceived significant community shortages of OMT services through primary care (
      0.45 +/- 0.50; P < .001) and specialty (-0.35 +/- 0.54; P < .001) physicians, and
      reported significant dissatisfaction with insurance coverage for OMT services (
      0.09 +/- 0.57; P = .001). These findings suggest the need for greater access to
      OMT services.

PMID- 11837338
TI  - Attitudes of osteopathic physicians toward physician-assisted suicide.
AB  - The use of physician-assisted suicide (PAS) in the care of terminally ill
      patients is controversial. While there are published surveys assessing the
      attitudes and views of physicians in certain specialties, both nationally and in
      targeted geographic areas, no such data are available specifically pertaining to
      osteopathic physicians, who deliver 9% of the primary care in the United States.
      This article describes a study whose purpose was to identify the views and
      perspectives of osteopathic physicians on PAS through a national survey.
      Questionnaires were forwarded to all board-certified internists who are members
      of the American College of Osteopathic Internists and all surgeons and a random
      sample of family physicians who are members of the American Osteopathic
      Association. Physicians were surveyed with initial and follow-up mailings. The 49
      item questionnaire was a modified version of the Physician Survey, Center for
      Ethics in Health Care: Oregon Health Sciences University. Of the 2910
      questionnaires that were mailed, 1028 were returned in a usable form, for a 35%
      response rate. Respondents were predominantly (81%) male and from all parts of
      the country. Most (58%) would not be willing to prescribe a medication for a
      competent, terminally ill patient to use with the primary intention of ending his
      or her own life, and most (55%) would oppose the legalization of PAS. Thirty
      three percent of osteopathic physicians admit to receiving requests by terminally
      ill patients for PAS. Most (53%) osteopathic physicians indicate that the
      osteopathic principle of holistic care has influenced their decision-making on
      this issue, and a significant minority (44%) responded that the osteopathic oath
      influenced their view on PAS. Religion and the degree of prayer frequency were
      important predictors of the decisions to support or oppose PAS. When compared to
      other physician surveys, this survey of osteopathic physicians demonstrates some
      similarities in response but also significant differences. These data suggest
      that osteopathic education and training may result in a perspective on PAS that
      reflects the distinctiveness of the osteopathic profession.

PMID- 11837339
TI  - Anthrax: a primary care physician's perspective.
AB  - Anthrax is a disease caused by Bacillus anthracis, a gram-positive, aerobic,
      spore-forming rod. It is also used as a biological weapon. The primary care
      physician will be the public's first line of defense in the event of a widespread
      anthrax exposure and will play a crucial role providing postexposure prophylaxis.
      Understanding the disease process will allow the primary care physician to play
      an essential role in protecting and educating the public. Accurate diagnosis and
      quick treatment will save many lives and help calm the panic following a
      biological attack.

PMID- 11837340
TI  - Symptoms associated with anthrax exposure: suspected "aborted" anthrax.
AB  - Anthrax is a naturally occurring organism with a low incidence of infection.
      There are no known cases of human-to-human transmission. Bioterrorism-related
      anthrax in the United States has been seen in three high-risk groups: (1) postal
      workers, (2) politicians and their staffs, and (3) the press. It appears as
      though the bioterrorism-related anthrax cases of fall 2001 have been transmitted
      through the US Postal Service. The authors present a case in which a person at
      high risk for anthrax exposure was inadequately treated and had symptoms that do
      not fall into any specific category of disease. It emphasizes the need for
      someone who has been started on prophylaxis for anthrax to complete a full 60-day
      course of treatment. It also shows the effectiveness of antibiotic therapy, even
      in those with high exposure to weaponized anthrax. Further, we would like to
      suggest that there may exist a new clinical entity of "aborted anthrax
      infection."

PMID- 11837343
TI  - Osteopathic approach may be helpful in war on terrorism.

PMID- 11837341
TI  - Pruritic urticarial papules and plaques of pregnancy: an unusual case.
AB  - Pruritic urticarial papules and plaques of pregnancy is considered the most
      common pruritic skin condition seen in pregnancy, and its classic presentation
      and treatment options have been well described. However, the exact etiologic
      factor of this condition remains obscure. This article presents an unusual case
      to demonstrate a variation in presentation of this disease as well as a unique
      course of treatment. The unusual progression of this case may render new insight
      regarding the etiologic factor of this disease.

PMID- 11837344
TI  - More on terrorism.

PMID- 11837345
TI  - Low-cost solution removes barriers.

PMID- 11837346
TI  - Stroke associated with alpha blocker therapy for benign prostatic hypertrophy.
AB  - Benign enlargement of the prostate is a malady of older males, reaching an
      estimated prevalence of 90% in patients aged over 70 years. Many of these
      patients are treated with alpha blockers, which can lower blood pressure
      significantly. We report on a 64-year-old man who developed a right hemiparesis
      after taking one dose of doxazosin 4 mg for prostatic symptoms. A CT scan of the
      brain and carotid ultrasound studies were normal. He recovered most of his
      neurological function within a few days. Ambulatory blood pressure monitoring on
      doxazosin 2 mg revealed a striking sleep blood pressure reduction.

PMID- 11837348
TI  - Diagnosis and management of laryngotracheal trauma.
AB  - Laryngotracheal trauma is life-threatening. We identified 23 patients between
      1992 and 1998 with laryngeal (12), tracheal (8), and combined injuries (3).
      Nineteen patients had penetrating trauma (gunshot wound, 12; stab wound, 7), and
      four patients had blunt injury. Flexible laryngoscopy identified the injury in 8
      of 12 patients (75%), and computer tomography scan was positive in 9 of 9
      patients (100%). Twelve of the 19 patients with penetrating wounds were managed
      by primary repair, 4 had endotracheal intubation without surgical repair, and 3
      were observed. No patient with a blunt tracheal injury required repair. Two had
      endotracheal intubation, and two were observed. A high index of suspicion is
      essential to identifying laryngotracheal injury. Computer tomography scan is a
      sensitive diagnostic test for laryngotracheal injury, and may be indicated
      despite normal flexible laryngoscopy. The decision to repair injuries or observe
      injuries is primarily based on respiratory distress and associated injuries.

PMID- 11837347
TI  - A trend analysis of organ transplantation among ethnic groups.
AB  - PURPOSE: This research provides public policy implications regarding organ
      resource allocation and increases public awareness of the current status of
      transplant use in various ethnic populations. PROCEDURES: Healthcare Cost and
      Utilization Project (HCUP), National Inpatient Sample (NIS) data were used to
      obtain a yearly estimate of the number of organ transplants by organ and by
      ethnic origin for 1988-1997. ICD-9-CM codes identified lung, heart, liver, and
      kidney organ-transplantation procedures. Each record in the sample was weighted
      by its respective discharge weight in order to extrapolate a national estimate.
      To assess whether there are significant differences among ethnic groups in organ
      transplantation rates over time, regression models were estimated for heart,
      liver, and kidney transplants. Transplantation rates were modeled as a function
      of time, ethnic origin, and interaction variables. FINDINGS: Examination of time
      trend graphs and regression analyses indicates that transplantation rates have
      not varied substantially across ethnic groups between 1988 and 1997. Rates for
      all groups, with the exception of Asians, exhibited similar time trends with
      little systematic variation. CONCLUSIONS: Further research is needed to determine
      whether variations exist due to organ availability versus prevalence of the
      disease.

PMID- 11837349
TI  - Does race predict short-term mortality after carotid surgery? The results of a
      meta-analysis.
AB  - Although African Americans are more likely to have an ischemic stroke and suffer
      a greater burden of stroke-related mortality and disability, they are less likely
      to have carotid surgery treatment than whites, even after accounting for clinical
      characteristics and ability to pay. Not surprisingly, little is known about their
      short- and long-term outcomes, including death, after undergoing carotid
      endarterectomy (CEA). The purpose of this study was to systematically review the
      published literature to clarify what role race has with respect to perioperative
      mortality risk following CEA. A search of MEDLINE (1966-May 2000), Scientific
      Citations (1945-May 2000), and the Cochrane Collaboration Stroke Group databases
      was performed to identify studies that related to African American-white
      differences for CEA mortality. Three studies met the specified eligibility
      criteria that allowed for the inclusion of 224,554 subjects (5,569 African
      Americans and 218,985 whites). Each showed some indication of increasing
      perioperative mortality risk for African Americans, but the findings were only
      significant for the studies of Hsia and colleagues (odds ratio (OR), 1.365; 95%
      confidence interval (CI), 1.164-1.600) and Huber and coworkers(28) (OR, 2.247;
      95% Cl, 1.367-3.695) but not for the study of Estes and colleagues (OR, 1.429;
      95% Cl, 0.827-2.469). After pooling the data, using a fixed-effects model, the OR
      was 1.429 (95% CI, 1.235-1.654). There was no evidence of significant
      heterogeneity between the studies and the random-effects model gave comparable
      results. African Americans, as compared to whites, appear to have a greater
      likelihood of short-term death following carotid surgery by more than 40%. This
      excess risk is possibly related to coexisting illness, which needs to be
      carefully weighed when considering a patient for CEA. Prospective studies are
      needed to further clarify these observed differences.

PMID- 11837350
TI  - Increasing participation of minorities in cancer clinical trials: summary of the
      "Moving Beyond the Barriers" Conference in North Carolina.
AB  - A day-long seminar was held at Wake Forest University School of Medicine to
      address barriers among ethnic minorities in cancer clinical trials and explore
      ways that individuals who design and conduct clinical trials could increase
      minority representation. Speakers addressed implications of under-representation
      of minorities and identified barriers to minority participation. State-wide focus
      group results were presented and revealed suspicion of medical research among
      minorities and the need for bridging to minority communities to improve
      participation in cancer clinical trials. Working groups assembled and identified
      barriers specific to trial design, providers, and participants. Attendees were
      encouraged to devise strategies within their institutions to overcome barriers to
      minority participation.

PMID- 11837351
TI  - African Americans and end of life care: yes to appropriate end of life supportive
      care, no to assisted suicide or euthanasia.

PMID- 11837352
TI  - Crisis in medico-legal death investigation.
AB  - There is a crisis in the field of medico-legal death investigation! This medical
      practice is one that most physicians do not think about until they are called in
      the middle of the night and informed that their patient has died and medical
      history is requested. Worse still, the trauma surgeon may need to explain why the
      patient did not survive the life-saving techniques used at his or her medical
      institution. The worst-case scenario is when the clinician is hit with a
      malpractice lawsuit.

PMID- 11837353
TI  - Association between reported education and intellectual functioning in an
      ethnically diverse adult psychiatric inpatient sample.
AB  - Patients' pre-existing survival skills, educational attainment, and intellectual
      functioning should be included in the development and implementation of treatment
      planning for adult psychiatric inpatients. When considering culturally diverse
      inpatient populations with possible cultural and language barriers, these
      variables may attain additional importance. Utilizing a sample (N = 60) primarily
      consisting of Asian/Pacific Islander inpatients, the present study investigated:
      (a) the rate at which professionals from different disciplines inquired about
      educational attainment; (b) the association between self-reported education and
      standardized measures of intelligence; and (c) the correspondence between
      different IQ scores. Axis 1 diagnoses included schizophrenia (N = 19; 32%),
      schizoaffective disorder or bipolar disorder (N = 23; 38%), and organic or
      substance-related disorders (N = 18; 30%). Thirty-five percent of the sample (N =
      21) had dual diagnoses. The results indicated that only psychologists who
      administered IQ tests consistently inquired about educational attainment. An
      expected overall positive association between self-reported education and
      standardized intelligence measures was found. High correlations between the Test
      of Nonverbal Intelligence, 2nd edition (TONI-2) and Wechsler Adult Intelligence
      Test-Revised (WAISQ-R) IQs suggested that both tests were valid in the assessment
      of intellectual functioning. Implications included the need for more systematic
      assessment and incorporation of pre-existing skill-based information and the
      utility of self-reported education and different measures of intellectual
      functioning (including TONI-2).

PMID- 11837354
TI  - Assessing screening mammography utilization in an urban area.
AB  - This study was conducted to determine the predictors of screening mammography
      among women 40 years old and older residing in South Central Los Angeles,
      California. The population is predominately African American and Hispanic. Using
      Computer Assisted Telephone Interview (CATI) software and the Random Digit
      Dialing (RDD) method, a 54-item, 20-min questionnaire was administered to 505
      women. All interviews were conducted in English or Spanish. The Health Belief
      Model provided the conceptual framework for the design of the questionnaire. A
      majority (81.8%) of the participants reported having at least one mammogram in
      their lifetime, with African Americans reporting the lowest rate (74.7%).
      Multiple logistic regression analyses found that 4 of the 23 independent
      variables assessed were predictive of ever users of mammography (p < 0.05), while
      6 independent variables were predictive of never users of mammography (p < 0.05).
      A significant finding of this study is the lower rate of screening mammography
      utilization in this sample compared to estimates for the general population. The
      results of this study also suggest that substantial improvements in the rate of
      screening mammography could be achieved if women in their 40s, who are without
      health insurance, were referred by their physicians to have affordable mammograms
      every year or two.

PMID- 11837355
TI  - Addressing medical audits. Part I - A strategy for achieving compliance: CMS,
      JCAHO, NCQA.

PMID- 11837356
TI  - Introduction: promoting and maintaining a reflective professional staff in a
      hospital-based social work department.
AB  - Promoting and sustaining a staff of reflective social work practitioners requires
      a supportive departmental structure and culture. Providing such support is a
      particular yet necessary challenge to social work administrators in the current
      health care environment. This article discusses an array of administrative
      strategies employed in one hospital social work department to promote reflective
      social work practice. More specifically, it describes the role of practice-based
      research in enhancing worker reflectiveness.

PMID- 11837357
TI  - Dialysis patient characteristics and outcomes: the complexity of social work
      practice with the end stage renal disease population.
AB  - This article describes a demonstration project designed to explore psychosocial
      risk and resiliency factors, social work interventions and health-related
      outcomes with dialysis patients. The study is unique in including an
      interdisciplinary research team to guide the process, using available data
      contained within the medical record and focusing on interventions and outcomes
      over time rather than at one or two points in patients' treatment histories. It
      demonstrates the complexity of practice with dialysis patients and the crucial
      role for social workers in enhancing patient outcomes. Secondary benefits of this
      methodology and implications for social work practice and research are discussed.

PMID- 11837358
TI  - Comparing social work's role in renal dialysis in Israel and the United States:
      the practice-based research potential of available clinical information.
AB  - This paper demonstrates the use of clinical data-mining in a study of social work
      interventions with dialysis patients in two countries, the US and Israel. We
      aimed to examine the role of social workers in improving kidney patient outcomes
      and to determine the potential of readily available patient information for
      studying this process. The findings showed considerable differences between the
      patient samples in both countries, as far as the socio-demographic background was
      considered. In spite of this, there were numerous similarities in the type of
      psycho-social problems and reactions, as well as the social workers'
      interventions. Differences which arose in various patient states and outcomes
      were examined in light of variations in the health care systems and socio
      cultural contexts of renal dialysis in both sites.

PMID- 11837359
TI  - Using available clinical information in practice-based research: mining for
      silver while dreaming of gold.
AB  - Social workers in health and mental health settings routinely collect and record
      enormous quantities of clinical information about clients, psycho-social
      interventions and client responses to these interventions. Despite its abundance
      and non-intrusiveness, social work researchers generally have ignored available
      clinical information, claiming that it is unreliable and subject to too many
      threats to validity to warrant serious consideration as a data source. Instead,
      many researchers have advocated "gold standard" experimental studies, employing
      standardized instruments and prospective data-collection. As a result, the
      research potential of retrospective studies based on available clinical
      information has been relatively unexplored and untested. This paper asserts that
      available clinical information can be converted into valuable retrospective, data
      bases for practice-based research studies. Exemplars of such studies in health
      and mental health settings are provided as are guidelines for their conduct.

PMID- 11837360
TI  - Mining clinical information in the utilization of social services: practitioners
      inform themselves.
AB  - When fully invested in applied studies regarding their own clinical and
      programmatic concerns, social work practitioners find that "mining" clinical
      information enriches their performance and services.

PMID- 11837361
TI  - Creating experimental analogs with available clinical information: credible
      alternatives to "gold-standard" experiments?
AB  - Comparison of the implementation and findings of a "gold standard" evaluation of
      social work intervention and its experimental analog based on available clinical
      information illustrates the strengths and weaknesses of each. From a practice
      research integration perspective, however, "clinical data-mining" may be a
      credible alternative to randomized controlled experiments.

PMID- 11837362
TI  - Screening for psychosocial risk in an urban prenatal clinic population: a
      retrospective practice-based research study.
AB  - Recognition of the need for early identification of risk factors led a "practice
      based research" (Epstein, 1995) team of social workers in the prenatal clinic at
      Mount Sinai to develop a standardized, comprehensive screening, monitoring and
      evaluation instrument for all patients in their service. To explore the effects
      of psychosocial risk factors empirically, available information collected from
      435 women screened with the original instrument between 1992-93 was converted
      into a quantitative data-base. The intention was to conduct a retrospective study
      of the prenatal patient population, including demographic characteristics,
      problems presented, social work interventions, and treatment outcomes. Among the
      findings anxiety and ambivalence related to pregnancy were significant risk
      factors. This model of social work service delivery is consistent with the focus
      of prenatal care as clinical preventative medicine.

PMID- 11837363
TI  - Psycho-social problems faced by "frequent flyers" in a pediatric diabetes unit.
AB  - This article describes an exploratory study of psychosocial factors common to,
      and associated with, frequently readmitted pediatric patients diagnosed with
      Insulin Dependent Diabetes Mellitus (IDDM). This practice-based study was
      undertaken by a social worker providing clinical services within a tertiary
      health-care pediatric diabetes unit at the Royal Children's Hospital, Melbourne
      (RCH), Australia and utilises available data obtained through retrospective
      record review in order to better inform service delivery. The study identified
      thirteen psychosocial factors having multiple occurrences within a small, but
      resource intensive, sub-population of the diabetes unit. The author discusses the
      possible contribution of each of these factors to poor metabolic control and
      frequent readmission to hospital, as well as the potential implications for
      future targeted prevention and treatment programs.

PMID- 11837364
TI  - Mining treatment termination data in an adolescent mental health service: a
      quantitative study.
AB  - This study utilizes available clinical information from client records to explore
      patterns of termination from mental health treatment among adolescents at an
      urban outpatient mental health center. The analysis focuses on how and why
      adolescents terminate from treatment and identifies variables associated with
      "acknowledged" and "unacknowledged" terminations. Findings indicate that
      termination was acknowledged infrequently, often a brief process that occurred
      almost as frequently by telephone as in the context of treatment. Contrary to
      "practice wisdom" concerning treatment termination, adolescents who "dropped out"
      without a "clinical process" reported considerably more engagement in treatment
      than those who acknowledged the termination of treatment. Recommendations for a
      more "open door" policy and a more flexible practice with adolescents are
      discussed.

PMID- 11837365
TI  - Social work practice with pre- and post-liver transplant patients: a
      retrospective self study.
AB  - This paper describes a retrospective, practice-based research study of social
      work interventions with liver transplant candidates and recipients. This study is
      based on a retrospective chart review conducted to examine psychosocial risk
      factors, interventions and medical outcomes. Psychosocial interventions provided
      to patients and families before and after transplant will be described as well as
      their relationship to medical outcomes. Research Findings and practice
      implications will be discussed.

PMID- 11837367
TI  - Women's experiences of stigma in relation to chronic fatigue syndrome and
      fibromyalgia.
AB  - Chronic fatigue syndrome and fibromyalgia are characterized by being difficult to
      diagnose and having an elusive etiology and no clear-cut treatment strategy. The
      question of whether these illnesses are stigmatizing was investigated through
      interviews with 25 women with these illnesses. The women experienced
      stigmatization primarily before receiving a diagnosis, and the diffuse
      symptomatology associated with the illnesses were significant for stigmatization.
      Stigma consisted of questioning the veracity, morality, and accuracy of patient
      symptom descriptions and of psychologizing symptoms. Coping with stigma was also
      explored and found to comprise both withdrawal and approach strategies, depending
      on the individual's circumstances and goals.

PMID- 11837368
TI  - The body remembers: grieving and a circle of time.
AB  - Using a phenomenological perspective, the author explored the experience of body
      memory following a significant loss. Ten women who had experienced the loss of a
      special loved one participated. Uncovered in this research were the hidden
      processes involved in grief work, which were cyclical and nonrational. Body
      memory experienced by each participant was unique in its expression, the common
      pattern being that it was relived as it was originally lived. This study brings
      to light processes of grieving that have been hidden and have remained silent in
      response to a social world that has been unwilling to accept a grieving process
      that extends out of the boundaries of the expected norm.

PMID- 11837369
TI  - The discursive properties of "hope": a qualitative analysis of cancer patients'
      speech.
AB  - The authors of this article question the usefulness of the empirico-realist
      search for a definitive definition of hope. Semistructured interviews on "do-not
      resuscitate" issues with 23 oncology clinic outpatients were tape-recorded,
      transcribed, and analyzed following grounded-theory methodology and discursive
      analytical methodology. Twelve patients spontaneously spoke about hope as
      objective or subjective, a burden or a resource. Hope represented an evaluation
      of empirical states of affairs or the wish for desired outcomes and was a warrant
      for action or an excuse for inaction. It was attributed to both patient and
      caregiver, to individuals or situations. Hope was present or future oriented,
      both vulnerable and enduring. The variety of versions of hope has implications
      for interactions between health care workers and patients. Recognizing a taxonomy
      of hope might prove more useful than searching for definitions.

PMID- 11837370
TI  - Nerves in northern Norway: the communication of emotions, illness experiences,
      and health-seeking behaviors.
AB  - The nature of nerves is the subject of a growing and dynamic body of
      anthropological research. The term nerves is often conceptualized as hard to
      define. Its meaning carries ambiguities, inconsistencies, and variation, although
      it is connected to reactions to the hardships of life. In the West, it is often
      associated with psychiatric problems. In this study, the researcher unveiled
      peoples' pragmatic use of the term nerves through diverse social settings in a
      coastal community in Northern Norway. The term was connected to psychological or
      psychiatric problems, privacy, and stigma, but had the capacity to communicate a
      continuum from normal emotional problems to severe mental illness. This study
      also showed the effect of the term in encounters between patients and
      professional health workers.

PMID- 11837371
TI  - "Unremarkable" recoveries: normalizing adversity and cancer survival.
AB  - Much of the existing popular literature suggests that survival from life
      threatening diseases encourages a process of self-transformation. Seventeen long
      term survivors of metastatic cancer were interviewed about the impact of a life
      threatening condition on their life stories. Contrary to the existing literature,
      which suggests such an event greatly transforms the individual, nearly all of
      those interviewed for this study framed their unusual recoveries as being largely
      unremarkable. Traditional North American cultural values, which normalize
      adversity, appear to bolster the participants' beliefs that one can have control
      over one's health and can even resist a recurrence of cancer.

PMID- 11837372
TI  - Coping with a child with Down syndrome: the experiences of mothers in Hong Kong.
AB  - Chinese mothers' experiences of parenting a child with Down syndrome were
      explored through semistructured interviews with 18 key informants selected by
      purposive sampling. Seven major themes were identified: unexpected birth of an
      abnormal child, acceptance of the child, special needs of the child, worry about
      the future, knowledge deficit, effect on the marital relationship, and social
      restrictions. The types of stressors changed over time according to the child's
      age, and coping strategies varied accordingly. Strategies frequently used were
      avoidance, self-reliance, and seeking social support. The particular problems
      faced by mothers of children with Down syndrome in Hong Kong were discussed in
      view of the sociocultural background of the region and the highly competitive
      nature of its society.

PMID- 11837373
TI  - Struggling for a tolerable existence: the meaning of men's lived experiences of
      living with pain of fibromyalgia type.
AB  - Chronic pain is a major health problem in Sweden because of its consequences in
      daily life. Fourteen men with fibromyalgia-type pain were interviewed regarding
      their experiences. A phenomenological hermeneutic method was used to interpret
      the transcribed interviews. Three major themes emerged: experiencing the body as
      an obstruction, being a different man, and striving to endure. Overall, the
      meaning of men's lived experience of chronic pain was experienced as change in
      the body, self, and relationships. Striving to live life required achieving
      balance during both calm and difficult phases of the illness--struggling for a
      tolerable existence. Information from this study could provide guidelines for
      health care staff members to give empathic and supportive care to men living with
      a long-term illness.

PMID- 11837375
TI  - Care-as-Worry, or "don't worry, be happy".
AB  - Care, or caring, is one of the central concepts in North American health science
      and nursing theories. Yet, experiential accounts of caring show dimensions of
      meaning that have received little attention in the literature. The author
      compares the meanings of the terms care and caring with their counterparts in
      other languages. He explores the significance of care-as-worry embedded in lived
      relations of caring and relates these concepts to ethical considerations
      surrounding health care. It is because of this felt "care-as-worry" that the life
      of care may be experienced as a complex moral-emotional relation of
      responsibility.

PMID- 11837374
TI  - The bodily suffering of living with severe psoriasis: in-depth interviews with 22
      hospitalized patients with psoriasis.
AB  - Psoriasis is one of the most common chronic skin diseases. The author presented
      results from a qualitative study focusing on patients with severe psoriasis in an
      acute phase and their experience of living with the disease. Twenty-two
      hospitalized patients with psoriasis were interviewed in depth. The interviews
      were consecutively analyzed according to grounded theory methodology. Bodily
      suffering emerged as a core variable in the data. Bodily suffering includes the
      following categories: the visible body, staying on an even keel, coping with an
      all-consuming disease, and social vulnerability. The results of this study
      indicate that the criterion for the management of soriasis should be the
      patients' own perception of the consequences of the disease.

PMID- 11837376
TI  - Qualitative research and the question of rigor.
AB  - In this article, the authors discuss the issue of rigor in relation to
      qualitative social research. It takes a critical focus on the inadequacy of
      applying a quantitative concept of rigor to evaluate qualitative research.
      Informed through the researchers' own experience, suggestions are made for a
      concept of rigor that meets the needs of qualitative research more adequately.
      Incorporating a notion of ethics, the authors develop a cluster of terms around
      which they argue that qualitative research can meaningfully speak about rigor:
      attentiveness, empathy, carefulness, sensitivity, respect, reflection,
      conscientiousness, engagement, awareness, and openness.

PMID- 11837377
TI  - Phenytoin toxicity with mandibular tremor secondary to intravenous
      administration.
AB  - The parenteral form of phenytoin is the most commonly used antiepileptic agent
      during the perioperative period in neurosurgery clinics. We report observations
      in a 52-year-old male patient with hypoalbuminemia and phenytoin intoxicity
      following 1 day preoperative administration and a 7-day postoperative intravenous
      administration of the drug with no modification of the oral dose. This report
      emphasizes the need for careful surveillance of phenytoin-induced toxicity during
      parenteral therapy, especially in debilitated patients.

PMID- 11837378
TI  - Hallucinations with therapeutic doses of clarithromycin.
AB  - OBJECTIVE: Hallucinations caused by adverse reactions to medication are not
      uncommon and a wide variety of drugs may be involved. We present a case of
      hallucinations caused by therapeutic doses of oral clarithromycin (500 mg b.i.d).
      CASE REPORT: A 32-year-old woman attended the Emergency Department of the
      hospital with severe visual hallucinations together with marked anxiety and
      nervousness following the second dose of clarithromycin, which was the only
      medication she was taking. The antibiotic was identified as the possible cause of
      the clinical manifestations and was stopped immediately. The patient did not
      require hospitalization and was discharged a few hours later with no signs of
      neurological disturbances. Clarithromycin was substituted by amoxycillin
      clavulanic acid (500/125 mg) t.i.d. CONCLUSIONS: The temporal relationship
      between commencement of antibiotic therapy and the appearance of hallucinations,
      together with the fact that the symptoms disappeared once the antibiotic was
      suspended, support a causal relationship between clarithromycin and the
      hallucinations. Further support for a causal relationship was obtained by
      application of Naranjo's algorithm which gave a likelihood level for causality of
      PROBABLE.

PMID- 11837379
TI  - PK-PD curve-fitting problems with the Hill equation? Try one of the 1-exp
      functions derived from Hodgkin, Douglas or Gompertz.
AB  - Non-linear phenomena are observed with enzyme kinetics, protein binding,
      pharmacokinetics or pharmacodynamics. The Hill equation, the Michaelis-Menten
      equation extended by a power coefficient, is traditionally used for sigmoid curve
      fitting. Sigmoid saturation phenomena can also be described by exponential
      functions (1-exp), extended by a power coefficient such as those derived by
      Hodgkin, Douglas or Gompertz. Comparing the 4 equations, the sigmoid 1-exp
      function in the form of Hodgkin and Huxley comes closest to the principle of
      simplicity and succinctness with regard to definition, slope and flexibility of
      the inflection point. To compare the applicability, a standardized sample of 250
      curves was generated by each I of the 4 equations and mutually fitted with the
      remaining 3. The Hill equation gives the closest fit with the data generated by
      the other functions. The Douglas variant exhibits the highest rate of
      convergence. The Gompertz function provides the basic feature of a baseline
      effect. CONCLUSION: The sigmoid functions investigated (Hill, Hodgkin, Douglas,
      Gompertz) have differing characteristics and can be used interchangeably for
      solving specific problems in non-linear modeling.

PMID- 11837380
TI  - Anthropometric data and acetylsalicylic acid pharmacokinetics.
AB  - The relationship between anthropometric data and pharmacokinetic characteristics
      of acetylsalicylic acid (ASA) after administration of a single oral dose of 500
      mg ASA, an oral and intravenous dose of 500 mg D,L-lysine-mono-acetylsalicylate
      (Lys-ASA) and an oral dose of 1,000 mg Lys-ASA were evaluated. Individual data
      from an open, randomized crossover trial in 13 healthy volunteers (age 18-50
      years, 6 female, 7 male, height 158-189 cm, weight 45-118 kg) were re-analyzed
      using a non-compartmental approach. The influence of body weight, height, body
      surface area and age on pharmacokinetic characteristics (Cmax, Tmax, AUClast,
      MRTlast, t 1/2, Cl, Vd) was assessed using the multiple regression method and
      pairwise multiple correlations were calculated. Multiple regression analysis
      showed significant multiple correlation coefficients of approximately 0.86 for
      Cmax (500 mg Lys-ASA i.v., 1,000 mg Lys-ASA per os and 500 mg ASA per os), Cl and
      AUClast (1,000 mg Lys-ASA per os). Standardized regression values (beta)
      reflected a major contribution for height, weight and body surface area, but age
      was not a relevant factor. Pairwise comparisons confirmed negative correlations
      between anthropometric characteristics and Cmax, AUClast and MRTlast and positive
      correlations between anthropometric data, Cl and Vd. In conclusion, apart from
      Tmax and t 1/2, all pharmacokinetic characteristics were influenced by body
      weight, height and body surface area. Whereas repeated administration of high
      doses in patients with low body weights may give rise to toxic effects, acute
      single dose administration would not lead to significant under-dosing in tall or
      stout patients.

PMID- 11837381
TI  - Bioequivalence study of a valsartan tablet and a capsule formulation after single
      dosing in healthy volunteers using a replicated crossover design.
AB  - AIM: Two formulations of valsartan (Diovan), 320 mg tablets and marketed 160 mg
      capsules, were evaluated for bioequivalence after single dosing. METHODS: The
      study was designed as a single-center, open-label, 2-treatment, 3-period,
      repeated-measure (replicated), randomized crossover comparison in 40 healthy
      volunteers, all of whom completed the study successfully. Valsartan was
      determined in plasma by HPLC with fluorescence detection after solid-phase
      extraction. RESULTS: Comparing the new 320 mg tablet with 2 x 160 mg of the
      marketed valsartan capsules taken at the same time, the ratios of the least
      square means for AUC(0-t), AUC(all), AUC(0-infinity) and Cmax were 1.11, 1.10,
      1.10 and 1.09, respectively. The 90% confidence intervals of the AUC and Cmax
      parameters were within the range of 0.80-1.25. CONCLUSIONS: Bioequivalence of the
      new 320 mg tablet with 2 marketed 160 mg capsules was demonstrated.

PMID- 11837382
TI  - Development and evaluation of an HPLC urinalysis screening test for occupational
      exposure to 3,4- and 3,5-dichloroanilines.
AB  - OBJECTIVE: In order to develop a screening test to detect human occupational
      exposure to aromatic amines such as 3,4-dichloroaniline (3,4-DCA) and 3,5
      dichloroaniline (3,5-DCA), we first investigated the urinary excretion of these
      highly toxic compounds in the rat. The study was performed after both oral and
      dermal application, even though contact with the skin is the major route of
      contamination in the workplace. The aim of this study was to develop a rapid
      screening test for risk assessment in the workplace. METHODS: An initial group of
      3 rats was treated with 40 microl of 3,4-DCA solution (30% in methanol), applied
      topically to the shaved dorsal skin. A second group of 3 rats were administered
      the same dose of the amine orally by gavage before urine sampling. The same
      procedure was performed with 3,5-DCA (2 other groups of 3 rats). The urine
      samples were collected for a period of 24 hours after treatment and the excretion
      of 3,4-DCA, 3,5-DCA was studied using a GC-MS and an HPLC method after urine
      extraction. The urine of 2 workers potentially exposed to the amines for a period
      of 161 and 147 days, respectively, was analyzed by the same methods with urine
      collection before and at the end of the work shift. RESULTS: The study of
      excretion in the rat showed that unchanged dichloroanilines and some metabolites
      were excreted 24 hours after administration of the amines. Based on these
      results, we propose an HPLC method for the screening of risk assessment in the
      workplace. The presence of 3,4-DCA and 3,5-DCA in the urine of workers showed
      that they were absorbing amines during the workshift. CONCLUSIONS: These results
      successfully allowed us to detect contamination due to 3,4-DCA and 3,5-DCA in
      exposed workers. The HPLC method described provides a satisfactory and sensitive
      procedure for urine screening in the assessment and monitoring of the
      occupational exposure to dichloroanilines.

PMID- 11837383
TI  - Moexipril shows a long duration of action related to an extended pharmacokinetic
      half-life and prolonged ACE inhibition.
AB  - OBJECTIVE: To characterize the lipophilic ACE inhibitor moexipril and its active
      metabolite moexiprilat regarding the duration of action, the susceptibility of
      the pharmacokinetics and pharmacodynamics to food intake and the concentration
      dependent effect. METHODS: Three independent, open, randomized studies were
      performed in healthy subjects using crossover or parallel-group designs. In the
      first study, pharmacokinetics (AUC, Cmax, tmax, t 1/2) and ACE inhibition (up to
      72 h) were investigated following single oral doses of 15 mg moexipril
      administered in the fasting and postprandial state (n = 24). The individual ACE
      inhibition data and plasma concentration data were fitted to an Emax model. In
      the second study, carried out in 52 volunteers, the pharmacokinetics were
      followed over 36 h following administration of 2 single oral doses of 15 mg
      moexipril. In the third study, the pharmacokinetics after multiple dosing of 15
      mg moexipril once daily for 5 days were investigated in 12 young and 12 elderly
      subjects. RESULTS: Moexiprilat tmax was 1.5-2 h with only minor differences
      between single and multiple dosing. Compared to fasting, the postprandial
      moexiprilat Cmax and AUC (ratio fed/fasted 58.0%; 90% CI 52.2-64.5%) were
      distinctly reduced (ANOVA p = 0.0001). Moexiprilat showed a biphasic elimination
      phase with an average t 1/2 of 29-30 h. In contrast to the alpha-phase, the
      plasma concentrations during the terminal elimination phase were not affected by
      food. A relationship between ACE inhibition and plasma concentration was not
      observed. The average ACE inhibition over 72 h was 71 % in the fasting state and
      74% in the postprandial state. ACE inhibition increased to about 80% after 24 h
      and decreased to about 60% at 72 h. The S-shaped concentration-effect curve
      indicated that a moexiprilat level of 1.3 ng/ml was sufficient to produce 50%
      inhibition of ACE. With repeated dosing there were no signs of drug accumulation
      and day-to-day drug levels were relatively constant. The trough concentrations at
      24 h did not fall below the limit of 1-2 ng/ml, i.e. a 50% ACE inhibition.
      CONCLUSION: Moexiprilat showed an extended duration of action owing to a long
      terminal pharmacokinetic half-life and produced a persistent ACE inhibition.
      Although the pharmacokinetics were partly influenced by food intake, ACE
      inhibition was not affected. This might be explained by a second compartment
      directly related to the ACE which is less prone to food effects and the reaching
      of a ceiling in the sigmoidal concentration-effect curve even with the lower Cmax
      concentrations associated with the postprandial state.

PMID- 11837384
TI  - HCMV pp67-mRNA detection by nucleic acid sequence-based amplification in renal
      transplant patients.
AB  - CMV infection is a major cause of morbidity and mortality following renal
      transplantation. Clinical diagnosis is difficult, and rapid and sensitive
      diagnostic methods are needed since antiviral therapy is available. The
      determination of the presence of viral transcripts is considered a direct marker
      of HCMV replication in vivo. In particular, it seems that the expression of late
      transcripts might better reflect active HCMV replication, dissemination and
      disease, and should cease upon effective blockage of viral polymerase by
      antiviral agents, such as gancyclovir. The unspliced pp67-mRNA can be
      specifically amplified using nucleic acid sequence-based amplification (NASBA) in
      a background of DNA. In the present study blood samples of forty-two renal
      transplant patients with active HCMV infection, demonstrated by pp65
      antigenaemia, were investigated to detect pp67-mRNA using the NASBA technique.
      Thirty-one pp65-antigenaemia positive patients resulted NASBA positive (73.8%)
      also in case of very low levels of antigenaemia; in 9/42 (21.4%) pp67-m-RNA was
      detected between 6 and 15 days before antigenaemia. Our results indicate that
      pp67-mRNA NASBA is a useful tool for the early diagnosis of active HCMV infection
      and for starting and modulating antiviral therapy, in addition to quantitative
      techniques such as antigenaemia, in renal transplant patients.

PMID- 11837385
TI  - Expression of alkaline phosphatase induces rapid and artificial mineralization in
      specific transformed Escherichia coli.
AB  - Matrix vesicles (MV) having high alkaline phosphatase (ALP) activity act as
      initiators of biological mineralization. Although bacteria have similar
      membranous structures to MV, ALP mediated mineralization has not been studied in
      bacterial cells. Escherichia coli was transformed with a bacterial ALP gene in
      this study. Recombinant E. coli overproducing ALP induced mineralization through
      hydrolysis of calcium-glycerophosphate (Ca-GP). Fourier transform infrared
      spectroscopy and electron microscopy combined with electron diffraction revealed
      newly formed hydroxyapatite mineral deposits. These findings suggest that
      hydrolysis of Ca-GP through ALP induced high Ca and Pi concentrations within
      bacterial cells followed by complete bacterial mineralization.

PMID- 11837386
TI  - Inactivated vaccine induces protection against Mycoplasma agalactiae infection in
      sheep.
AB  - The efficacy of an inactivated oil-emulsion vaccine against Mycoplasma agalactiae
      was evaluated by an experimental infection of sheep. The vaccinated sheep
      developed high levels of antibodies and, following challenge, they did not
      develop any clinical signs of disease and the mycoplasmas were not detected,
      either by isolation trials or PCR assays carried out both on nasal swabs and milk
      specimens. The unvaccinated-challenged sheep showed typical signs of M.
      agalactiae infection and bacterial shedding. The results obtained indicate a good
      efficacy of the vaccine in eliciting protection against M. agalactiae infection.

PMID- 11837387
TI  - Genomic heterogeneity of environmental and clinical aeromonads.
AB  - Thirty-three isolates of Aeromonas from environmental sources and clinical
      samples were tested and the results, obtained using the pulsed field gel
      electrophoresis (PFGE) technique, were compared with those obtained by
      biochemical typing. On the basis of their biochemical characteristics 31 strains
      was assigned to one of the recognised groups or species within the Aeromonas
      genus and 2 strains to the species Vibrio fluvialis. These latter were
      nevertheless found to belong to the Aeromonas genus on the basis of the
      chromosomal DNA analysis. Among the clinical isolates the biochemical analysis
      showed greater uniformity. A low correlation between molecular and traditional
      typing methods was observed with a wider heterogeneity at the genomic level. The
      results showed the difficulty of discriminating Aeromonas isolates by
      conventional biochemical methods. The genomic analysis performed by PFGE can be a
      more effectual technique, which can be used for epidemiological and ecological
      studies of the microorganisms belonging to the Aeromonas group.

PMID- 11837388
TI  - Bacterial etiology of otitis media with effusion; focusing on the high positivity
      of Alloiococcus otitidis.
AB  - The etiology of otitis media with effusion (OME) is unclear. The bacterial
      analyses of middle ear effusion (MEE) in OME may reveal important information
      regarding its etiology. Alloiococcus otitidis, Heamophilus influenzae,
      Streptococcus pneumoniae and Moraxella catarrhalis were investigated by using
      microbiologic culture and a multiplex PCR method in the middle ear fluid of 32
      children (54 samples) with chronic OME. PCR yielded positive results in 18
      (33.3%) middle ear effusions while culture resulted positive for 3 (5.6%). The
      PCR method detected A. otitidis in 10 (18.5%) specimens, H. influenzae in 7
      (13%), M. catarrhalis in 4 (7.4%) and S. pneumoniae in 2 (3.7%) specimens. The
      multiplex PCR method enhances the detection rate significantly compared to that
      of the conventional culture method. A. otitidis is the most common detected
      pathogen in the MEE of the OME.

PMID- 11837389
TI  - Selection of bacteriocin producer strains of lactic acid bacteria from a dairy
      environment.
AB  - Two strains showing bacteriocin production were selected from a total of 206
      lactic acid bacteria isolated from samples of milk, milk serum, whey and homemade
      cheeses in Southern Cordoba, Argentina. This property was detected by means of
      well diffusion assays. The strains were identified as Enterococcus hirae and
      Enterococcus durans. The protein nature of those substances was proved by showing
      their sensitivity to type IV and XXV proteases, papaine, trypsin, pepsin and K
      proteinase. The bacteriocins inhibited the growth of Listeria monocytogenes,
      Bacillus cereus, Clostridium perfringes and two strains of Staphylococcus aureus,
      an A-enterotoxin and a B-enterotoxin producers. All of these bacteria are common
      pathogens usually associated with food borne diseases (ETA). These lactic acid
      bacteria or their bacteriocins could be suitable candidates for food preservation
      and specially useful in the our regional dairy industry.

PMID- 11837390
TI  - Bacteriocin-producing Lactobacillus sake as starter culture in dry sausages.
AB  - One hundred and fifty-two strains of Lactobacillus spp and Micrococcus spp,
      isolated from dry sausages, were screened for inhibitory activity. Two of the
      strains assayed of the genus Lactobacillus showed bactericidal activity. They
      were able to inhibit Listeria monocytogenes, Listeria seeligeri, Listeria
      innocua, Lactobacillus alimentarius and Lactobacillus bavaricus. The strains of
      Escherichia coli, Salmonella bradford and Salmonella newlands, Staphylococcus
      aureus, Bacillus cereus, Pseudomonas aeruginosa, Serratia marcescens were
      resistant. Their antimicrobial activity was due to peptides detectable in the
      culture broths and inactivated by treatment with proteolytic enzymes. Using
      bacteriocin-producing Lactobacillus sake as starter cultures in dry sausages
      could be promising in the food industry.

PMID- 11837391
TI  - Microbiological indoor air quality in healthy buildings.
AB  - There is a growing interest in indoor air quality for a better quality
      environment both at home and at work because many people spend at least 80% of
      their time indoors. The aim of our study was to evaluate the indoor concentration
      of airborne bacteria and fungi in a University auditorium, in an office of public
      buildings and in an apartment in the presence and in absence of building's
      occupants, building materials and furnishings. The concentrations of airborne
      bacteria and fungi were determined using a Surface Air System (SAS). In presence
      of people and furnishings the average air concentrations of bacteria (University
      auditorium: 925-1225 CFU m(-3); office: 493 CFU m(-3); apartment: 92-182 CFU m(
      3)) were higher than in absence (respectively: 190-315 CFU m(-3); 126 CFU m(-3);
      66-80 CFU m(-3)). The average air concentrations fungal were higher in presence
      of people and furnishings (University auditorium: 1256-1769 CFU m(-3); office:
      858 CFU m(-3); apartment: 147-297 CFU m(-3)) than in absence (respectively: 301
      431 CFU m(-3); 224 CFU m(-3); 102-132 CFU m(-3)). The obtained data can be
      considered as a step to identify acceptable levels for bioaerosols in common
      indoor environments.

PMID- 11837392
TI  - Bioconversion of poultry wastes I-factors influencing the assay and productivity
      of crude uricase by three uricolytic filamentous fungi.
AB  - The optimum temperature for biomass yield and uricase production by uricolytic
      fungi, Aspergillus terreus. A. flavus and Trichoderma sp. was at 30 degrees C.
      The time required for maximum production of uricase and biomass yield was 4 days
      for two Aspergillus species and 6 days for Trichoderma sp. The optimum pH was at
      6.4 for A. terreus and pH 6.6 for both A. flavus and Trichoderma sp. The maximum
      fungal biomass yield was achieved in medium supplemented with 4% poultry waste.
      The best carbon sources for the production of uricase and mycelia yield were
      glycerol, sucrose and maltose by A. terreus, A. flavus and Trichoderma sp.,
      respectively. Uric acid was found to be the best nitrogen source for production
      and activity of uricase by the three tested fungi. The addition of some vitamins
      to the culture media increased the maximum biomass yield of all the isolates, but
      did not significantly increase uricase production.

PMID- 11837393
TI  - Persistent colonization and transient suppression of DTH responses in an estrogen
      dependent vaginal candidosis murine model.
AB  - Recurrence of vaginal candidosis in women of childbearing age has been attributed
      to several predisposing factors including the presence of significant amounts of
      estrogen in the reproductive tract. In this study, the effect of estrogen on the
      level of C. albicans colonization, persistence of infection and suppression of
      DTH responses was investigated in an estrogen-dependent vaginal candidosis murine
      model. Mice were first injected subcutaneously with 0.5 mg of estradiol valerate
      72 hours prior to C. albicans intravaginal inoculation and at weekly intervals
      thereafter for a period of up to 4 weeks; the inoculum consisted of 2 x 10(7)
      stationary-phase C. albicans blastoconidia in a volume of 20 microl. C. albicans
      colonization was evaluated in the spleen, liver, kidney, small intestine and
      reproductive tract of estrogen-treated and control mice 72 hours following
      inoculation, DTH responses were evaluated 2 and 5 weeks following primary
      inoculation and persistence of infection was evaluated at days 2, 3, 4, 8, 12, 19
      and 26 post inoculation. Estrogen-treated mice exhibited higher levels of C.
      albicans colonization compared with control mice; this was most evident in the
      small intestine and reproductive tract. Estrogen treatment resulted in pronounced
      suppression of C. albicans-specific DTH responses; in that average footpad
      swelling was 4.7 mm in untreated mice compared with 2.3 mm in estrogen-treated
      mice. Long-term estrogen treatment resulted in the persistence of infection; in
      contrast, C. albicans infection resolved by day 8 post inoculation in untreated
      mice. DTH responses assayed 5 weeks post primary inoculation in treated mice were
      on average 4.1 mm, this was similar to that observed in untreated mice tested for
      DTH response 2 and 5 weeks post primary inoculation. These results suggest that,
      on the one hand, estrogen has an enhancing effect on C. albicans colonization and
      persistence of infection. On the other, estrogen seems to suppress DTH responses
      within the first 2 weeks post infection; persistence of infection under the
      influence of estrogen, however, seems to coexist with detectable systemic cell
      mediated immunity.

PMID- 11837394
TI  - Relations between hydrophobicity tested by three methods and surface chemical
      composition of Escherichia coli.
AB  - The cell surface hydrophobicity of three strains of Escherichia coli cultured in
      liquid medium and on solid medium was measured using various methods including
      adsorption to pxylene, partition of cells in a polyethylene glycol/dextran
      (PEG/DEX) two phase system and contact angle measurements. The percentage
      adsorbed to pxylene ranged from 1.6% to 67% and the percentage of cells in
      polyethylene glycol phase ranged from 19% to 64%. The contact angle data of less
      than 40 degrees C revealed a hydrophylic character of the E. coli strains studied
      here. No relations were found between paraxylene/water partitioning, PEG/DEX
      partioning and water contact angles. The linear correlation coefficients between
      the results of the three hydrophobicity assays and the elemental concentration
      ratios obtained by X-ray photoelectron spectroscopy (XPS) were calculated. A
      linear correlation was found between the contact angles and the O/C ratios
      (r=0.91) and the N/C ratios (0.67). The adsorption to pxylene correlates better
      with N/C ratios (0.88) but does not correlate with O/C ratios (0.46). However,
      this test correlates with N/P ratios (0.79). No relation was obtained between
      partition in PEG/DEX system and any elemental concentration ratios. The surface
      composition determined by XPS was converted into a molecular composition in terms
      of proteins, polysaccharides, and hydrocarbon-like compounds. The
      proteins/polysaccharides and the hydrocarbons/polysaccharides seems to determine
      the contact angle of E. coli but not the adsorption to paraxylene or partition in
      the PEG/DEX system.

PMID- 11837395
TI  - HIV-1: a case of RT67 deletion in a multi-treated non responder patient.
AB  - The early detection of mutations in the HIV-1 polymerase is a key point in the
      management of anti-retroviral therapy. While nucleotide substitutions and
      insertions have been well and frequently desribed in literature as linked to drug
      resistance, deletions have been rarely observed and desribed (ART67, Imamichi et
      al.). The aim of this study is to describe a case of deletion of three
      nucleotides in the RT gene (ART67) of a multi-treated HIV-1 infected patient. As
      this deletion has not been detected by the oligoprobe assay, the phenotyping test
      was used to support therapy but without an appreciable success in terms of viral
      load. Then a sequencing based genotyping system was used to analyse the viral
      polymerase and a novel deletion was found at codon 67 of RT gene.

PMID- 11837396
TI  - Beta-lactamase production by Escherichia coli under different growth conditions.
AB  - Facultative anaerobic bacteria, such as Escherichia coli, are more resistant to
      cephalosporin antibiotics during anaerobic growth. Strict anaerobic ambience
      reduces beta-lactamase production or the enzyme affinities for their substrates.
      A different balance between DNA gyrase and topoisomerase I activity, during
      aerobic and anaerobic growth condition, could be related to the bacteria
      behavior.

PMID- 11837397
TI  - Epidemiology of bloodstream infections and time to detection of positive blood
      cultures: an evaluation of the automated BacT/Alert and BACTEC 9240 systems.
AB  - Data of 3,097 blood culture sets processed with the BacT/Alert system in 1997
      were compared to those of 3,158 blood culture sets processed with BACTEC 9240 in
      1999. Agents responsible for bloodstream infections (BSI) were detected in 15.9%
      and 20.0% of blood cultures in 1997 and 1999, respectively. The incidence of BSI
      was 9.3 (1997) vs. 11.3 (1999) per 1,000 admissions. In both years, S. aureus was
      the most frequent isolate, followed by E. coli. Overall, the mean detection time
      (MDT) obtained with the BACTEC 9240 was significantly shorter than that of the
      BacT/Alert. Significant MDT differences were found for all organisms, except for
      Enterobacteriaceae (12.7 vs. 10.6 h). With both systems, over 95% positive
      samples were detected within 3 days, indicating that a 4-day incubation protocol
      may disclose most BSI agents. Thus, the added speed of the BACTEC 9240 allowed a
      particularly fast clinical management of septic patients.

PMID- 11837398
TI  - Virulence genes in halophilic Vibrio spp. isolated in common mussels.
AB  - Twenty-five Vibrio strains belonging to nine different species, isolated in
      common mussels, were examined for the presence of different virulence genes:
      ctxA, tcpA, toxR, toxS, ace, zot and vpi previously found in pathogenic Vibrio
      cholerae strains. Our results suggest that there is a wide dissemination of
      Vibrio cholerae virulence genes among the various Vibrio species tested. This
      finding raises the question of whether a different approach should be taken to
      study "environmental" Vibrio strains.

PMID- 11837399
TI  - Imipramine plus cognitive-behavioral therapy for school refusal.

PMID- 11837400
TI  - Ten-year review of rating scales. I: overview of scale functioning, psychometric
      properties, and selection.
AB  - OBJECTIVE: As part of the Journal's 10-year Research Update Reviews, a series of
      articles will be presented on the role of rating scales in child and adolescent
      psychiatry. The first article in the series summarizes principles underlying
      scale functioning. METHOD: Sources were reviewed regarding testing theory, scale
      development, variability in scale functioning, psychometric properties, and scale
      selection. The extracted information was adapted to issues in child and
      adolescent psychiatry. RESULTS: Rating scales can make major contributions to
      understanding youths' needs. They provide easy and efficient measurement of
      psychopathology and quantify underlying constructs for comparison across youths,
      time, and applications. Although multiple factors may affect a scale's
      functioning, these factors can be understood and managed by considering the goals
      of measurement and basic psychometric principles. CONCLUSIONS: Potential users of
      rating scales should not blindly assume that a well-known scale will meet the
      measurement needs for a particular application. Rather, they can relatively
      easily educate themselves regarding the appropriate use of rating scales. This
      article provides the background information needed to evaluate scales for
      intended applications. It will also assist in reviewing the individual scales
      presented in subsequent articles in this series.

PMID- 11837402
TI  - Preparation for practice: child and adolescent psychiatry graduates' assessment
      of training experiences.
AB  - OBJECTIVE: To assess the perceived effectiveness of child and adolescent
      psychiatry residency training in preparing recent graduates for practice in
      diverse work settings. METHOD: Analysis of survey data of 392/797 (49.2%) of all
      U.S. child and adolescent psychiatrists graduating from training in 1996-1998 and
      on the mailing list of the American Academy of Child and Adolescent Psychiatry.
      RESULTS: Overall, respondents reported high-quality training. They felt least
      prepared by training for their present practice in the areas of administration
      and leadership skills, medical economics and business skills, complex
      psychopharmacology, treatment of children with complicated developmental
      disabilities, and cognitive-behavioral therapy. They felt overtrained in
      consultation-liaison to pediatrics and inpatient work. Clinical experiences,
      supervisors/mentors and a well-rounded program were cited as most crucial to
      training. Suggestions for improvement included more "real-world" administration
      and leadership exposure, enhanced supervision, and improved didactics. Most felt
      training prepared them for their specialty board examinations. CONCLUSIONS:
      Recruitment and training of highly skilled child and adolescent psychiatrists is
      a national priority. The present database assessment of efficacy in preparing
      graduates for diverse career practices may inform training programs and policy.
      An enhanced training curriculum in leadership and administrative skills and
      medical economics is recommended.

PMID- 11837401
TI  - A survey of early-career child and adolescent psychiatrists: professional
      activities and perceptions.
AB  - OBJECTIVE: To assess the career paths and work perceptions of early-career child
      and adolescent psychiatrists in the United States. METHOD: Analysis of survey
      data of 392/797 (49.2%) of all U.S. child and adolescent psychiatrists graduating
      from training in 1996-1998 and on the mailing list of the American Academy of
      Child and Adolescent Psychiatry. RESULTS: Slightly more than half of those
      surveyed were women, and most were in their late thirties, white, married, and
      living in the geographic area in which they trained, with a median income for
      full-time workers between $121,000 and $150,000. Those with educational debt owed
      an average of $69,741. The sample was generally very satisfied with their work.
      They identified clinical work, variety, autonomy, and making a difference as the
      best aspects, and managed care, paperwork, and overwork as the least desirable
      aspects. The bulk of hours worked were in solo private practice, public sector,
      and group practice, with children and adolescents making up 73% of patients
      treated. The most common treatment modality was medication management.
      CONCLUSIONS: The present study uses a database approach to defining current
      practice and workforce issues among early-career child and adolescent
      psychiatrists. These data may facilitate objective discussion about public
      policies concerning workforce priorities, barriers, and facilitators to
      recruitment in this understaffed field.

PMID- 11837403
TI  - Risperidone treatment in children and adolescents with autism: short- and long
      term safety and effectiveness.
AB  - OBJECTIVE: Atypical neuroleptics, including risperidone, are used to treat
      children with autism, despite limited efficacy and safety data. Many clinicians
      believe that risperidone will not induce dyskinesias in children. The authors
      investigated open risperidone treatment in children with autism and included
      findings on dyskinesias. METHOD: The sample included 22 outpatients (mean age =
      7.1 years) diagnosed with autism (DSM-IV). Treatment consisted of a 1-month short
      term phase followed by a 6-month long-term phase. At the end of the long-term
      phase, drug was discontinued, and the need for further drug treatment and the
      occurrence of withdrawal dyskinesias were assessed. Measures included the
      Clinical Global Impressions (CGI), Children's Psychiatric Rating Scale (CPRS),
      and the Abnormal Involuntary Movement Scale. RESULTS: The mean risperidone dosage
      was 1.2 mg/day. Overall, the children had significant clinical improvement as
      assessed by the CPRS and CGI. Untoward effects included sedation, increased
      appetite, and weight gain. Two of 13 (15.4%) children treated long-term developed
      mild, reversible withdrawal dyskinesias when risperidone was discontinued. No
      child developed dyskinesias on risperidone. CONCLUSIONS: Risperidone shows
      promise as a treatment in autism. However, withdrawal dyskinesias were noted.
      Further assessment of the risk of risperidone-related dyskinesias is indicated.

PMID- 11837404
TI  - Anxiety after severe pediatric closed head injury.
AB  - OBJECTIVE: To assess the frequency of anxiety symptoms and disorders 1 year after
      severe pediatric closed head injury (CHI) and to determine the risk factors
      associated with these postinjury outcomes. METHOD: Ninety-seven subjects were
      prospectively followed for 1 year after severe CHI (Glasgow Coma Scale Score = 3
      8). Assessments of preinjury and 1-year postinjury psychiatric status and
      psychosocial adversity were conducted. Frequency of anxiety symptoms and
      disorders 1 year after injury were the outcome measures. Data collection occurred
      between 1992 and 1996. RESULTS: There was a significant increase in the total
      number of anxiety symptoms after injury compared with before injury. The most
      frequent symptoms were overanxious symptoms, followed by obsessive-compulsive
      symptoms, separation anxiety symptoms, and simple phobia symptoms. There was a
      trend toward an increase in the frequency of overanxious disorder after injury.
      Preinjury anxiety symptoms correlated positively with postinjury anxiety symptoms
      and disorders. Younger age at injury correlated positively with postinjury
      anxiety symptoms. CONCLUSIONS: One year after severe CHI, children are at risk
      for a variety of anxiety symptoms and, possibly, overanxious disorder. Preinjury
      anxiety and younger age at injury are risk factors for these disturbances.

PMID- 11837405
TI  - Clinical predictors of posttraumatic stress disorder after closed head injury in
      children.
AB  - OBJECTIVE: To describe injury, demographic, and neuropsychiatric characteristics
      of children who develop posttraumatic stress disorder (PTSD) and posttraumatic
      stress symptoms (PTSS) after closed head injury (CHI). METHOD: Ninety-five
      children with severe CHI and amnesia for the event were prospectively followed
      for 1 year. Structured interviews were administered twice to the parents: shortly
      after injury to cover the child's premorbid status, and 1 year after injury. The
      child was also interviewed twice: shortly after injury to cover current status,
      and 1 year after injury. Outcome measures were diagnostic status (PTSD by parent
      or child) and symptom severity (PTSS by parent or child). RESULTS: Twelve
      children developed PTSD by 1 year after injury, 5 according to parent report, 5
      according to child report, and 2 according to both parent and child report.
      Predictors of PTSD at 1 year post-CHI included female gender and early post-CHI
      anxiety symptoms. Predictors of PTSS at 1 year post-CHI were (1) premorbid
      psychosocial adversity, premorbid anxiety symptoms, and injury severity; and (2)
      early post-CHI depression symptoms and nonanxiety psychiatric diagnoses.
      CONCLUSIONS: PTSD developed in 13% of children with severe CHI accompanied by
      traumatic amnesia. Predictors of PTSD and PTSS after CHI, according to parent and
      child report, are consistent with predictors of PTSD and PTSS that develop after
      non-head injury trauma.

PMID- 11837406
TI  - Toward an empirical definition of pediatric PTSD: the phenomenology of PTSD
      symptoms in youth.
AB  - OBJECTIVE: To examine the frequency and intensity of posttraumatic stress
      disorder (PTSD) symptoms and their relation to clinical impairment, to examine
      the requirement of meeting all DSM-IV symptom cluster criteria (i.e., criteria B,
      C, D), and to examine the aggregation of PTSD symptom clusters across
      developmental stages. METHOD: Fifty-nine children between the ages of 7 and 14
      years with a history of trauma and PTSD symptoms were assessed with the Clinician
      Administered PTSD Scale for Children and Adolescents. RESULTS: Data support the
      utility of distinguishing between the frequency and the intensity of symptoms in
      the investigation of the phenomenology of pediatric PTSD. Children fulfilling
      requirements for two symptom clusters did not differ significantly from children
      meeting all three cluster criteria with regard to impairment and distress.
      Reexperience (cluster B) showed increased aggregation with avoidance and numbing
      (cluster C) and hyperarousal (cluster D) in the later stages of puberty.
      CONCLUSIONS: Frequency and intensity of symptoms may both contribute to the
      phenomenology of pediatric PTSD. Children with subthreshold criteria for PTSD
      demonstrate substantial functional impairment and distress.

PMID- 11837407
TI  - Victimization and PTSD in a Danish national youth probability sample.
AB  - OBJECTIVE: To investigate the prevalence of traumatic events and life events in
      relation to posttraumatic stress disorder (PTSD). METHOD: In a Danish national
      representative sample of 390 eighth-grade students with a mean age of 14.5 years,
      20 prevalent potential traumatizing and distressing events were described, along
      with the psychological impact of these events. RESULTS: Eighty-seven percent of
      the females and 78% of the males were exposed to at least one event. The most
      common events were the death of a family member, threat of violence, or serious
      accidents. The most distressing subjective events were rape, suicide attempts,
      death in the family, serious illness, and childhood abuse. Gender, parents'
      education, and living with a single parent were associated with specific events.
      The estimated lifetime prevalence of PSTD was 9.0%, whereas another 14.1% reached
      a subclinical level of PTSD. After exposure, females suffered from PTSD twice as
      often as males. Being exposed to multiple traumatic events was associated with an
      increase in PTSD. CONCLUSION: The findings in this study suggest substantial
      mental health problems in adolescents who are associated with various types of
      victimization.

PMID- 11837408
TI  - Child and adolescent problems predict DSM-IV disorders in adulthood: a 14-year
      follow-up of a Dutch epidemiological sample.
AB  - OBJECTIVE: Few studies exist that examine continuities between child and adult
      psychopathology in unselected samples. This study prospectively examined the
      adult outcomes of psychopathology in an epidemiological sample of children and
      adolescents across a 14-year period. METHOD: In 1983, parent ratings of
      behavioral and emotional problems were obtained for 1,578 children and
      adolescents aged 4 through 16 years from the Dutch general population. At follow
      up, 14 years later, subjects were reassessed with a standardized DSM-IV
      interview. RESULTS: High levels of childhood problems predicted an approximate 2-
      to 6-fold increased risk for adulthood DSM-IV diagnoses. The associations between
      specific childhood problems and adulthood diagnoses were complex. Social Problems
      in girls predicted later DSM-IV disorder. Rule-breaking behavior in boys
      predicted both mood disorders and disruptive disorders in adulthood. CONCLUSIONS:
      High levels of childhood behavioral and emotional problems are related to DSM-IV
      diagnoses in adulthood. The strongest predictor of disorders in adulthood was
      childhood rule-breaking behavior. Attention Problems did not predict any of the
      DSM-IV categories when adjusted for the associations with other Child Behavior
      Checklist scales.

PMID- 11837409
TI  - Emergence of gender differences in depression during adolescence: national panel
      results from three countries.
AB  - OBJECTIVE: Although the gender gap in depression among adults is well
      established, the age at which this phenomenon appears during adolescence is less
      clear. To address this, the authors present a cross-national examination of the
      emergence of the gender gap in depression during adolescence using national
      longitudinal panel data from Canada, Great Britain, and the United States.
      METHOD: The two-wave, 1994-1996 Canadian National Population Health Survey uses a
      diagnostic measure across a 24-month interval, providing 12-month prevalence
      rates of major depressive disorder. The British Youth Panel measures depressive
      symptomatology across five annual waves beginning in 1995. The two-wave, 1995
      1996 National Longitudinal Study of Adolescent Health uses a measure of
      depressive symptomatology across a 12-month interval. RESULTS: Females have
      significantly higher rates of depression for each sample overall. When samples
      are decomposed by age, the gender gap in depression consistently emerges by age
      14 across all three national samples, irrespective of the measure used or whether
      categorical cutoffs or untransformed scale scores are used to assess depressive
      symptomatology. CONCLUSIONS: There is a consistent pattern in the onset of the
      gender gap in depression at age 14 across all three countries and measures. This
      consistency provides important etiologic clues concerning underlying causes of
      depression and identifies at what age diagnosis, treatment, and intervention
      strategies should be directed.

PMID- 11837410
TI  - Epidemiology of depressive symptoms in the National Longitudinal Study of
      Adolescent Health.
AB  - OBJECTIVE: To describe the range of depressive symptoms reported by adolescents
      in a nationally representative U.S. sample and to examine factors associated with
      persistent depressive symptoms. METHOD: Secondary analysis was done on National
      Longitudinal Study of Adolescent Health (AddHealth) data from 13,568 adolescents
      who completed the initial survey in 1995 and follow-up 1 year later. Main
      outcomes of Center for Epidemiologic Studies-Depression Scale (CES-D) scores were
      analyzed by chi2 comparisons and sample-weighted logistic regression. RESULTS:
      Over 9% of adolescents reported moderate/severe depressive symptoms at baseline
      (CES-D > or = 24). Females, older adolescents, and ethnic minority youths were
      more likely to report depressive symptoms at baseline. Only 3% of adolescents
      with low initial CES-D scores (CES-D < 16) developed moderate/severe depressive
      symptoms at follow-up. Factors associated with persistent depressive symptoms at
      1-year follow-up included: female gender, fair/poor general health, school
      suspension, weaker family relationships, and health care utilization. Other
      factors, including race and socioeconomics, did not predict persistent depressive
      symptoms. CONCLUSIONS: Depressive symptoms are common in adolescents and have a
      course that is difficult to predict. Most adolescents with minimal symptoms of
      depression maintain their status and appear to be at low risk for depression;
      however, adolescents with moderate/severe depressive symptoms warrant long-term
      follow-up and reevaluation.

PMID- 11837411
TI  - Religiosity, depression, and physical maturation in adolescent girls.
AB  - OBJECTIVE: To assess the impact of physical maturation on the protective
      qualities of religiosity against depression in adolescent girls. METHOD: Subjects
      were 3,356 adolescent girls (mean age 16.0, SD = 1.8) interviewed in 1995 as part
      of the Wave I In-Home Version of the North Carolina Adolescent Health Study.
      Maturation was assessed on the basis of self-report of secondary sexual
      characteristics and age at onset of menstruation. Religiosity was assessed on the
      basis of personal devotion, personal conservatism, institutional conservatism,
      and participation in religious community. Logistic regression analyses were
      conducted with each variable of religiosity used to predict depression,
      controlling for age and ethnicity. RESULTS: Personal devotion and participation
      in religious community were associated with a 19% to 26% decreased likelihood of
      depression in non-highly mature girls and a relatively more robust 32% to 43%
      decreased likelihood of depression in highly mature girls. Personal conservatism
      and institutional conservatism were associated with a 17% to 24% decreased
      likelihood of depression among non-highly mature girls, but were not associated
      with depression in highly mature girls. CONCLUSION: Physical maturation may be
      associated with the protective qualities of religiosity against depression in
      adolescent girls.

PMID- 11837412
TI  - Clinical problem solving: the case of Matthew, part II.

PMID- 11837413
TI  - Genetics of childhood disorders: XXXV. Autoimmune disorders, part 8: animal
      models for noninflammatory autoimmune disorders of the brain.

PMID- 11837414
TI  - General design classifications.
AB  - This column described the general design classifications of between-groups,
      within-subjects, and mixed designs. Remember that in between-groups designs, each
      participant is in only one group or condition. In within-subjects or repeated
      measures designs, on the other hand, each participant receives all the conditions
      or levels of the independent variable. In mixed designs, there is at least one
      between-groups independent variable and at least one within-subjects independent
      variable. In classifying the design, do not consider the dependent variable(s).
      The classifications and descriptions presented in this column are for difference
      questions, using the randomized experimental, quasi-experimental, and comparative
      approaches to research. Appropriate classification and description of the design
      are crucial for choosing the appropriate inferential statistic, which is the
      topic of the next column and several to follow.

PMID- 11837415
TI  - Phytoextraction of toxic metals: a review of biological mechanisms.
AB  - Remediation of sites contaminated with toxic metals is particularly challenging.
      Unlike organic compounds, metals cannot be degraded, and the cleanup usually
      requires their removal. However, this energy-intensive approach can be
      prohibitively expensive. In addition, the metal removing process often employs
      stringent physicochemical agents which can dramatically inhibit soil fertility
      with subsequent negative impacts on the ecosystem. Phytoremediation has been
      proposed as a cost-effective, environmental-friendly alternative technology. A
      great deal of research indicates that plants have the genetic potential to remove
      many toxic metals from the soil. Despite this potential, phytoremediation is yet
      to become a commercially available technology. Progress in the field is hindered
      by a lack of understanding of complex interactions in the rhizosphere and plant
      based mechanisms which allow metal translocation and accumulation in plants. In
      this paper, four research areas relevant to metal phytoextraction from
      contaminated soil are reviewed. The review concludes with an assessment of the
      current status of technology deployment and suggestions for future
      phytoremediation research.

PMID- 11837416
TI  - Environmental concentrations of agricultural herbicides: 2,4-d and triallate.
AB  - The herbicides 2,4-D (2,4-dichlorophenoxyacetic acid) and triallate [S-2,3,3
      trichloroallyl di-isopropyl(thiocarbamate)] are extensively used to control
      broadleaf and wild oat (respectively) weed infestations in Canadian cereal crops.
      In 1990, for example, more than 3.8 million kg of 2,4-D and 2.7 million kg of
      triallate were applied in the three prairie provinces (Alberta, Saskatchewan, and
      Manitoba). Maximum air concentrations of these two herbicides during the summers
      of 1989 and 1990 near Regina, Saskatchewan, were 3.90 ng m(-3) (2,4-D) and 60.04
      ng m(-3) (triallate). Concentrations of these two herbicides were also measured
      in bulk atmospheric deposition (wet plus dry) and in farm pond water and
      associated surface film. Maximum measured levels of 2,4-D were 3550 ng m(-2) d(
      1) (bulk deposition), 332 ng m(-2) (surface film), and 290 ng L(-1) (pond water).
      Maximum levels of triallate were 2300 ng m(-2) d(-1) (bulk deposition), 212 ng m(
      2) (surface film), and 500 ng L(-1) (pond water). The highest quantities of the
      herbicides tended to be found during or immediately after the time of regional
      application. The movement of the herbicides in the environment will be discussed
      in relation to the four matrices studied.

PMID- 11837417
TI  - Impact of methylene chloride on microorganisms and phenanthrene mineralization in
      soil.
AB  - This study investigated the effects of the quantity of methylene chloride, used
      as a carrier solvent for phenanthrene when added to soil, on phenanthrene
      mineralization kinetics, soil phospholipid fatty add profiles (PLFA), and
      phenanthrene distribution. Methylene chloride dosages of 25 microL/g soil or more
      resulted in an enrichment of saturated PLFAs, suggesting soil microorganisms had
      adjusted their cell membranes in response to the solvent. A greater fraction of
      phenanthrene mineralized when spiked in 5 microL/g than in 25 microL/g methylene
      chloride suggesting that the methylene chloride became toxic to phenanthrene
      degrading organisms in soil. Phenanthrene was more equally distributed among 0.1
      g soil subsamples if spiked in 25 than 5 or 1 microL methylene chloride per gram
      soil. Thus the amount of methylene chloride used to spike phenanthrene in soil
      strongly impacted the mineralization kinetics, phenanthrene distribution, and
      microbial community in soil. Because a variety of spiking methods are used in
      biodegradation research, scientists should consider the quantity of solvents used
      when comparing results among different studies.

PMID- 11837418
TI  - Genotoxicity is unrelated to total concentration of priority carcinogenic
      polycyclic aromatic hydrocarbons in soils undergoing biological treatment.
AB  - A solid-phase microbiological assay was used to determine the changes in
      genotoxicity associated with sequestration or biodegradation of carcinogenic
      compounds in contaminated soils. The concentration of six carcinogenic polycyclic
      aromatic hydrocarbons (PAHs) did not change in 59 d in sterile soil, but the
      genotoxicity declined markedly. In a soil undergoing bioremediation in the field
      for 147 d or biodegradation in the laboratory for 180 d, the concentrations
      either changed little or declined at different rates, but the genotoxicity
      increased followed by a decline. The genotoxicity of a second soil declined as a
      result of biological treatment. The data show that genotoxicity of contaminated
      soils may be unrelated to the concentration of carcinogenic PAHs because of aging
      or new mutagens formed during biological treatment.

PMID- 11837419
TI  - Natural uranium and thorium distributions in podzolized soils and native
      blueberry.
AB  - Plant uptake of radionuclides is one of many vectors for introduction of
      contaminants into the human food chain. Thus, it is critical to understand soil
      plant relationships that control nuclide bioavailability. Our objectives in this
      study were to (i) determine the extent of U and Th uptake and cycling by
      blueberry (Vaccinium pallidum Aiton) in native habitat and (ii) identify the soil
      properties and processes that contribute most to U and Th bioavailability in this
      system. We collected composite samples of plant leaves and stems, and samples
      from surface (AE) horizons and from the upper part of the Bs horizon at two
      sites. Concentration ratios (CRs) for U and Th were calculated for all plant
      tissues, using both the AE and Bs horizons as the base. Soil concentrations of U
      ranged from 16 to 25 microg g(-1), with a mean of 21.1 microg g(-1). Soil
      concentrations of Th ranged from 14 to 97 microg g(-1), with a mean of 41.8
      microg g(-1). Mean U concentrations were 8.65 x 10(-3) microg g(-1) in leaf
      tissue, and 7.95 x 10(-3) microg g(-1) in stem tissue. Mean Th concentrations
      were 1.59 x 10(-1) microg g(-1) in leaf tissue, and 9.10 x 10(-2) microg g(-1) in
      stem tissue. Blueberry plants are cycling both U and Th in this system, with Th
      cycling occurring to a greater extent than U. In addition, Th was translocated
      preferentially to plant leaves while U concentrations showed little preferential
      translocation. Uranium uptake, however, seemed more sensitive than Th uptake to
      soil properties.

PMID- 11837420
TI  - Trends in agriculture in the LEASEQ watersheds, 1975-1995. Lake Erie Agricultural
      Systems for Environmental Quality.
AB  - County-level agricultural statistics were aggregated at the watershed level to
      provide estimates of trends in land use and agricultural management in the Maumee
      and Sandusky River watersheds during the period 1975-1995. Average farm size
      increased by 40% or more, but the number of farms decreased by nearly 40%; the
      total land area in agriculture also decreased, but only by about 7%. Conservation
      tillage increased from virtually nothing to nearly 50% of cropland in corn (Zea
      mays L.) and soybean [Glycine max (L.) Merr.]; most of the change is due to
      adoption of no-till soybean. The Conservation Reserve Program has enrolled more
      than 75,000 hectares, but this represents less than 5% of total farmland. The
      great majority of land classified as highly erodible has been placed under
      treatment during the study period. Cropland in soybean has increased; land in
      wheat (Triticum aestivum L.) and hay has decreased. Cropland in corn has
      decreased in the Maumee watershed and increased slightly in the Sandusky
      watershed. Average per-hectare yields of corn, soybean, wheat, and hay have
      increased by 10 to 40%. Fertilizer phosphorus sales increased until about 1980
      and have declined significantly since then; fertilizer nitrogen follows a similar
      but less pronounced pattern. The decreases are more substantial in the Maumee
      watershed than in the Sandusky. Manure use for fertilizer has also declined
      significantly.

PMID- 11837421
TI  - Assessment of uncertainty and risk in modeling regional heavy-metal accumulation
      in agricultural soils.
AB  - Present agricultural land use and atmospheric deposition may lead to heavy-metal
      accumulation rates in soils that may violate soil quality standards in the
      future. To undertake suitable preventive measures against heavy-metal enrichment,
      flux balances in agroecosystems and their uncertainties have to be assessed. For
      this reason we developed an empirical stochastic model, PROTERRA-S, that
      considers heavy-metal inputs through agricultural management as well as outputs
      by crop removal and leaching on a regional scale. In this manuscript we describe
      application of PROTERRA-S to the Sundgau region in Switzerland. Considering
      uncertainty in informational and natural variability, large variations of the
      aggregated regional cadmium and zinc balances were found, with standard
      deviations that were of the same order of magnitude as their average values.
      Uncertainty in the simulated net zinc flux originated mainly from uncertainty in
      the zinc concentrations of manure and crops and from uncertainty in atmospheric
      deposition of zinc. For cadmium, the main contribution to the total uncertainty
      came from uncertainty in crop concentration, regression functions to estimate
      Freundlich parameters, atmospheric deposition, and from spatial variation of soil
      pH and cation exchange capacity (CEC). For both zinc and cadmium, informational
      uncertainty in input data were large, indicating that significant uncertainty
      reduction could be achieved by additional data collection campaigns. A monetary
      risk value for the regional zinc accumulation rate in Sundgau was calculated to
      be on the order of 22 million Euro.

PMID- 11837422
TI  - Effects of ash application on cadmium concentration in small mammals.
AB  - In order to assess the effects of wood ash application to forests on small
      mammals, we collected bank voles (Clethrionomys glareolus) and common shrews
      (Sorex araneus) from a forest area in southern Finland. Part of the sample
      population was from sites that had been treated with ash 1.5 years earlier, part
      from untreated control sites. The ash increased the soil pH and gave an average
      cadmium load in soil of 44 g ha(-1). When comparing treated and control areas, we
      found slightly but significantly lower Cd concentrations in vole muscle, liver,
      and kidney from treated plots, whereas the Cd concentrations in shrew tissues
      were greater in animals from treated plots. In voles we detected an increase in
      Cd concentrations during the 45-d sampling period in treated and untreated plots.
      The relative weight of kidneys was greater from the ash-treated areas than
      untreated areas for both voles and shrews. The difference in Cd concentrations
      between the voles and shrews could be explained by the different food habits.

PMID- 11837423
TI  - Copper and zinc speciation in the solution of a soil-sludge mixture.
AB  - Only a small fraction of the transition metals content in sludge-amended soils is
      soluble, and yet this fraction is a major contributor to the mobility and
      bioavailability of the metals. The chemical species of zinc (Zn) and copper (Cu)
      in the soluble fractions of soil-sludge mixtures were characterized with respect
      to their charge, molecular weight, and stoichiometry using ion exchange resin and
      gel chromatography procedures. The change in the metals' species with time after
      sludge application was followed for 100 d. Copper in the water extracts of the
      sludge-sand mixtures was found almost exclusively in low molecular weight (below
      1000 Da) complexes. Higher molecular weight (around 2500 Da) dissolved organic
      carbon (DOC) was present in the extracts as well, but this DOC fraction exhibited
      little complexation. Copper was present in the extracts mainly as negatively
      charged species throughout the incubation period, and zinc tended to form zwitter
      ions. As incubation progressed, the relative content of positively charged Zn in
      solution increased. Complexation capacity of DOC in sludge water extract,
      extrapolated to infinite dilution, was 8.75 mM Ca g(-1) DOC. When the
      complexation capacity of the extract is near saturation, a mean Cu-DOC complex
      can be defined. It consists of 1.9 Cu atoms attached to DOC species containing
      5.6 C atoms. Thus, the organic Cu complexes consist primarily of about two Cu
      ions attached to DOC species containing only five or six C atoms. Amino acids and
      small peptides or polycarboxylic acids, such as citric acid, thus may be
      important complexing agents of the metal.

PMID- 11837425
TI  - Phosphorus transport in overland flow in response to position of manure
      application.
AB  - Phosphorus (P) loss in overland flow varies with spatial distribution of soil P,
      management, and hydrological pathways. The effect of flow time, flowpath length,
      and manure position on P loss in overland flow from two central Pennsylvania
      soils packed in boxes of varying length (0.5, 1.0, 1.5, 2.75, and 4.0 m long x 15
      cm wide x 5 cm deep) were examined by collecting flow samples at 5-min intervals
      for 30 min (50 mm h(-1) rainfall) without and with 75 kg P ha(-1) applied as
      swine (Sus scrofa) manure over 0.5 m of the box slope length at distances of 0 to
      3.5 m from the downslope collection point. Dissolved reactive P concentration was
      more closely related to the proportion of clay in sediment of overland flow
      before (r = 0.98) than after (r = 0.56) manure application. This was attributed
      to the transport of larger, low-density particles after applying manure. The
      concentration of dissolved and particulate P fractions decreased with increasing
      flowpath length, due to dilution rather than sorption of P by surface soil during
      overland flow. Total P loss (mainly as particulate P) from the Watson channery
      silt loam (fine-loamy, mixed, active, mesic Typic Fragiudult) was more than from
      Berks channery silt loam (loamy-skeletal, mixed, active, mesic Typic Dystrudept),
      even with manure applied. Thus, while P loss in overland flow is affected by
      where manure is applied relative to flowpath length, initial soil P concentration
      should not be discounted when looking at areas of potential P loss within a
      watershed.

PMID- 11837424
TI  - The effects of throughfall manipulation on soil leaching in a deciduous forest.
AB  - The effects of changing precipitation on soil leaching in a deciduous forest were
      examined by experimentally manipulating throughfall fluxes in the field. In
      addition to an ambient treatment (AMB), throughfall fluxes were reduced by 33%
      (DRY treatment) and increased by 33% (WET treatment) using a system of rain
      gutters and sprinklers on Walker Branch Watershed, Tennessee. Soil leaching was
      measured with resin lysimeters in the O horizons and with ceramic cup lysimeters
      in the E (25 cm) and Bt (70 cm) horizons. Large and statistically significant
      treatment effects on N fluxes were found in the O horizons (lower N fluxes in the
      DRY and higher N fluxes in the WET treatment). Together with the greater O
      horizon N content observed in the DRY treatment, this suggested that N was being
      immobilized at a greater rate in the DRY treatment than in the AMB or WET
      treatments. No statistically significant treatment effects on soil solution were
      found in the E horizons with the exception of (Ca2+ + Mg2+) to K+ ratio.
      Statistically significant treatment effects on electrical conductivity (EC), pH,
      Ca2+, Mg2+, K+, Na+, SO4(2-), and Cl- were found in the Bt horizons due to
      differences between the DRY and other treatments. Despite this, calculated fluxes
      of Ca2+, Mg2+, K+, Na+, SO4(2-), and Cl- were lowest in the DRY treatment. These
      results suggest that lower precipitation will cause temporary N immobilization in
      litter and long-term enrichment in soil base cations whereas increased
      precipitation will cause long-term depletion of soil base cations.

PMID- 11837426
TI  - Sensitivity and first-step uncertainty analyses for the preferential flow model
      MACRO.
AB  - Sensitivity analyses for the preferential flow model MACRO were carried out using
      one-at-a-time and Monte Carlo sampling approaches. Four different scenarios were
      generated by simulating leaching to depth of two hypothetical pesticides in a
      sandy loam and a more structured clay loam soil. Sensitivity of the model was
      assessed using the predictions for accumulated water percolated at a 1-m depth
      and accumulated pesticide losses in percolation. Results for simulated
      percolation were similar for the two soils. Predictions of water volumes
      percolated were found to be only marginally affected by changes in input
      parameters and the most influential parameter was the water content defining the
      boundary between micropores and macropores in this dual-porosity model. In
      contrast, predictions of pesticide losses were found to be dependent on the
      scenarios considered and to be significantly affected by variations in input
      parameters. In most scenarios, predictions for pesticide losses by MACRO were
      most influenced by parameters related to sorption and degradation. Under specific
      circumstances, pesticide losses can be largely affected by changes in
      hydrological properties of the soil. Since parameters were varied within ranges
      that approximated their uncertainty, a first-step assessment of uncertainty for
      the predictions of pesticide losses was possible. Large uncertainties in the
      predictions were reported, although these are likely to have been overestimated
      by considering a large number of input parameters in the exercise. It appears
      desirable that a probabilistic framework accounting for uncertainty is integrated
      into the estimation of pesticide exposure for regulatory purposes.

PMID- 11837427
TI  - Evaluating agricultural nonpoint-source pollution programs in two Lake Erie
      tributaries.
AB  - During the past three decades, numerous government programs have encouraged Lake
      Erie basin farmers to adopt practices that reduce water pollution. The first
      section of this paper summarizes these state and federal government agricultural
      pollution abatement programs in watersheds of two prominent Lake Erie
      tributaries, the Maumee River and Sandusky River. Expenditures are summarized for
      each program, total expenditures in each county are estimated, and cost
      effectiveness of program expenditures (i.e., cost per metric ton of soil saved)
      are analyzed. Farmers received nearly $143 million as incentive payments to
      implement agricultural nonpoint source pollution abatement programs in the Maumee
      and Sandusky River watersheds from 1987 to 1997. About 95% of these funds was
      from federal sources. On average, these payments totaled about $7000 per farm or
      about $30 per farm acre (annualized equivalent of $2 per acre) within the
      watersheds. Our analysis raises questions about how efficiently these incentive
      payments were allocated. The majority of Agricultural Conservation Program (ACP)
      funds appear to have been spent on less cost-effective practices. Also,
      geographic areas with relatively low (high) soil erosion rates received
      relatively large (small) funding.

PMID- 11837428
TI  - Degradation of 14C-atrazine bound residues in brown soil and rendzina fractions.
AB  - The remobilization and the fate of 14C-ring labeled atrazine (6-chloro-N2-ethyl
      N4-isopropyl-1,3,5-triazine-2,4-diamine) bound residues was examined in relation
      with the turnover of natural soil organic matter. Soil fractions of a brown soil
      and a rendzina were incubated under controled laboratory conditions. The
      mineralization of natural organic matter and atrazine-bound residues was
      respectively estimated by the amounts of CO2 and 14CO2 evolved during the
      incubation. The remobilization and distribution of 14C residues among the soil
      organic fractions were achieved after physical-chemical extractions of the
      samples. Comparisons of samples in abiotic and biotic conditions allowed us to
      assess the influence of microbial activity on the fate of atrazine-bound
      residues. The mineralization curves showed that natural organic matter and
      atrazine-bound residues had similar decomposition patterns. After 100 d of
      incubation, 0.8 to 3.6% of total organic C was evolved as CO2, while only 0.1% of
      the initial radioactivity was mineralized as CO2, and 7 to 15% was becoming
      extractable with water and methanol. Few differences were observed in the
      distribution of residues within organic compounds for both fractions of the
      rendzina, except a decrease of the 14C radioactivity of the 50- to 5000-microm
      fraction and a slight increase of that of humin. For the 0- to 5000-microm brown
      soil fraction, increased radioactivity in humin at the expense of humic (HA) and
      fulvic (FA) acids was detected after incubation, while for the 0- to 50-microm
      fraction more radioactivity was recovered with FA.

PMID- 11837429
TI  - Fate of polydimethylsilicone in biosolids-amended field plots.
AB  - This research examined the fate of polydimethylsilicones (PDMS) in agricultural
      test plots amended with municipal biosolids. This 4 yr field study involved
      addition of 0, 15, and 100 Mg ha(-1) of municipal biosolids, which contained
      ambient concentrations of PDMS (1272 mg kg(-1) biosolids), to corn and soybean
      test plots. Soil samples collected at intermittent time intervals were analyzed
      for soil water, soil organic C, extractable PDMS and PDMS hydrolysis products.
      Above normal precipitation during the field study maintained soil water levels in
      excess of 100 g kg(-1) for most of the testing period of 1994-1998. Under these
      conditions half-lives for PDMS (based on field dissipation data) ranged from 876
      to 1443 d. When biosolids amended soil samples were brought into the laboratory
      and subjected to more rapid drying, >80% of the PDMS was transformed to lower
      molecular weight hydrolysis products within 20 d. No difference in relative PDMS
      transformation rates were evident for soils that received PDMS in the form of a
      biosolids amendment or directly dosed to the soil (in the absence of biosolids)
      indicating little if any effect of direct PDMS-biosolids interactions on PDMS
      transformation rates. These results support that the overriding factor
      controlling the fate of PDMS in field soils is the soil moisture content.

PMID- 11837430
TI  - Fate of pesticides in tropical soils of Brazil under field conditions.
AB  - The potential of pesticides for nonpoint ground water pollution depends on their
      dissipation and leaching behavior in soils. We investigated the fate of 10
      pesticides in two tropical soils of contrasting texture in the Brazilian Cerrado
      region near Cuiaba during an 80-d period, employing topsoil dissipation studies,
      soil core analyses, and lysimeter experiments. Dissipation of pesticides was
      rapid, with field half-lives ranging from 0.8 to 20 d in Ustox and 0.6 to 11.8 d
      in Psamments soils. Soil core analyses showed progressive leaching of polar
      pesticides in Psamments, whereas in Ustox pesticides were rapidly transported to
      40 cm soil depth regardless of their sorption properties, suggesting that
      leaching was caused by preferential flow. In lysimeter experiments (35 cm soil
      depth), cumulative leaching was generally low, with < or = 0.02% and < or = 0.19%
      of the applied amounts leached in Ustox and Psamments, respectively. In both
      soils, all pesticides but the pyrethroids were detected in percolate at 35 cm
      soil depth within the first 6 d after application. Cumulative efflux and mean
      concentrations of pesticides in percolate were dosely correlated with their
      Groundwater Ubiquity Score (GUS). The presence of alachlor (2-chloro-2', 6'
      diethyl-N-methoxymethylacetanilide), atrazine (2-chloro-4-ethylamino-6
      isopropylamino-1,3,5-triazine), metolachlor [2-chloro-N-(2-ethyl-6-methylphenyl)
      N-(2-methoxy-1-methylethyl)acetamide], simazine [2-chloro-4,6-bis(ethylamino)
      1,3,5-triazine], and trifluralin (2,6-dinitro-N,N-dipropyl-4
      trifluoromethylaniline) throughout the soil profile and in percolate of wick
      lysimeters at 95 cm soil depth indicated that a nonpoint pollution of ground
      water resources in tropical Brazil cannot be ruled out for these substances.

PMID- 11837431
TI  - Photochemistry and photoinduced toxicity of acifluorfen, a diphenyl-ether
      herbicide.
AB  - Photochemistry studies can be helpful in assessing the environmental fate of
      chemicals. Photochemical reactions lead to the formation of by-products that can
      exhibit different toxicological properties from the original compound. For this
      reason the photochemical behavior of the herbicide acifluorfen (5-[2-chloro-4
      (trifluoromethyl)phenoxy]-2-nitrobenzoic acid) in the presence of different
      solvents was studied. Photochemical reactions were carried out using a high
      pressure mercury arc and a solar simulator. Kinetic parameters and quantum yields
      were determined. The identification of photoproducts was performed by mass
      spectrometry and [1H] nuclear magnetic resonance (NMR). Nitrofluorfen, hydroxy
      nitrofluorfen, 2-chloro-4-(trifluoromethyl)phenol, 5-trifluoromethyl-5'
      nitrodibenzofuran, and other derivatives were identified. The photochemical
      reactions were also carried out in the presence of either a singlet or a triplet
      quencher, and in the presence of either a radical initiator or a radical
      inhibitor. Substances used as inhibitors of the excited levels T1 and S1 showed
      that photodegradation of acifluorfen begins from a singlet state S1 through a
      pi,pi* transition. The role of free radicals in the photodegradation of
      acifluorfen was determined and a radical mechanism was proposed. Toxicity tests
      against Daphnia magna Strauss showed that acifluorfen was not toxic at a
      concentration of 0.1 mM; however, photoproducts formed after 36 h of UV exposure
      of the herbicide induced a remarkable toxicity to the test organism.

PMID- 11837432
TI  - Combined effect of natural organic matter and surfactants on the apparent
      solubility of polycyclic aromatic hydrocarbons.
AB  - Both natural organic matter (NOM) and surfactants are known to enhance the
      apparent aqueous solubility of hydrophobic organic contaminants (HOCs) in aqueous
      systems. In this study, the combined effect of NOM and surfactants on enhancing
      the solubility of HOCs was investigated, since both may occur and affect the fate
      and transport of HOCs in natural aqueous environments. Experimental results
      indicated that the apparent solubility of naphthalene, phenanthrene, and pyrene
      in NOM and anionic surfactant solution was lower than their solubility in NOM
      solution alone. However, the apparent solubility of an HOC in NOM and nonionic
      surfactant solution is almost the same as the sum of the HOC's solubility in NOM
      solution plus its solubility in nonionic surfactant solution. The observation
      that apparent aqueous solubility of HOCs in NOM and anionic surfactant solution
      is decreased is probably due to the fact that the cations that are released when
      the anionic surfactant dissociates may form ion pairs with acidic or phenolic
      groups associated with the NOM. This serves to increase the size of hydration of
      these groups, thereby decreasing the effective size of the nonpolar moieties
      associated with the NOM, and thus decreasing hydrophobic partitioning of the HOCs
      into the NOM. The results presented here will help us to understand the effect of
      NOM and surfactants on the fate and transport of HOCs in aquatic systems.

PMID- 11837433
TI  - Bioavailable phosphorus in runoff from alfalfa, smooth bromegrass, and alfalfa
      smooth bromegrass.
AB  - Runoff from sloping landscapes cropped with established alfalfa (Medicago sativa
      L.) may contain bioavailable P (BAP) which accelerates eutrophication of surface
      water bodies. Such BAP exists as either dissolved reactive P (DRP) or
      bioavailable reactive particulate P (BPP). We hypothesized that before and after
      harvest, sod-forming smooth bromegrass (Bromus inermis Leyss.) or alfalfa-smooth
      bromegrass mixtures would have less BAP, DRP, and BPP runoff losses than
      taprooted alfalfa. Swards established in 1992 near Lancaster, WI were subjected
      to a 72 mm simulated rainfall applied for 1 h in 1993 and 1994 to forage regrowth
      at 4 and 6 wk after first harvest and immediately (0 wk) after second harvest.
      Hourly BAP losses for all sward types were 82% less when 1.5 Mg ha(-1) of forage
      dry matter was present. High DRP losses (>0.050 kg ha(-1)) were associated with
      high DRP concentrations (>7.1 micromol L(-1)) and high surface soil P
      concentrations (>59 mg kg(-1)) resulting from broadcast maintenance P fertilizer.
      High BPP losses (>0.035 kg ha(-1)) were associated with high runoff volumes (>24
      mm) and sediment concentrations (>2 g L(-1)). Summed over all 6 rainfall
      simulations, total BAP loss was only 0.07 kg ha(-1) at the 6 wk stage of regrowth
      compared with 0.35 at 4 wk, and 0.41 at 0 wk. Moreover, there was no significant
      difference between sward types for DRP concentration, DRP loss, or BAP loss. We
      conclude that avoiding excessive defoliation was more effective at reducing BAP
      losses than specific forage species selection.

PMID- 11837434
TI  - Tracing sources of sulfur in the Florida Everglades.
AB  - We examined concentrations and sulfur isotopic ratios (34S/32S, expressed as
      delta34S in parts per thousand [/1000] units) of sulfate in surface water, ground
      water, and rain water from sites throughout the northern Everglades to establish
      the sources of sulfur to the ecosystem. The geochemistry of sulfur is of
      particular interest in the Everglades because of its link, through processes
      mediated by sulfate-reducing bacteria, to the production of toxic methylmercury
      in this wetland ecosystem. Methylmercury, a neurotoxin that is bioaccumulated,
      has been found in high concentrations in freshwater fish from the Everglades, and
      poses a potential threat to fish-eating wildlife and to human health through fish
      consumption. Results show that surface water in large portions of the Everglades
      is heavily contaminated with sulfate, with the highest concentrations observed in
      canals and marsh areas receiving canal discharge. Spatial patterns in the range
      of concentrations and delta34S values of sulfate in surface water indicate that
      the major source of sulfate in sulfur-contaminated marshes is water from canals
      draining the Everglades Agricultural Area. Shallow ground water underlying the
      Everglades and rain water samples had much lower sulfate concentrations and
      delta34S values distinct from those found in surface water. The delta34S results
      implicate agricultural fertilizer as a major contributor to the sulfate
      contaminating the Everglades, but ground water under the Everglades Agricultural
      Area (EAA) may also be a contributing source. The contamination of the northern
      Everglades with sulfate from canal discharge may be a key factor in controlling
      the distribution and extent of methylmercury production in the Everglades.

PMID- 11837435
TI  - Point- and nonpoint-source pesticide contamination in the Zwester Ohm catchment,
      Germany.
AB  - Reducing pesticide loads in surface waters implies identifying the pathways
      responsible for the pollution. The current study documents the pesticide
      contamination of the river Zwester Ohm, a 4917-ha catchment in Germany with 41%
      of the land used for crop production. Discharges and concentrations of 19
      pesticides were measured continuously at three locations for 15 mo. The load
      detected at the outlet of the catchment amounted to 9048 g a.i. The losses
      represent 0.22% of the pesticides applied by the farmers. The contamination
      showed a seasonal pattern following the pesticide application times. The
      wastewater treatment plant system (WWTPS) in the catchment (two wastewater
      treatment plants [WWTP], 14 combined sewer overflows (CSO), four CSO tanks) emits
      during dry weather periods purified sewage and during storm events sewage mixed
      with stormwater runoff into the river. The contribution by the WWTPS to the
      pesticide load was defined as point-source pollution (PSP). The load was
      dominated by PSP with at least 77% of the total pollution. No significant
      interdependencies between intrinsic properties of the pesticides,
      hydrometeorological factors, and the loads occurring in the stream could be
      found. Therefore, it is not possible to predict PSP for other catchments based on
      the results from this study. Whereas 65% of the total load entered the river via
      the WWTP, a portion of 12% was attributed to the CSO. The study points out that
      the influence of CSO on PSP should be taken into account in future catchment
      studies in areas with comparable agricultural structure.

PMID- 11837436
TI  - Phosphorus exchangeability and leaching losses from two grassland soils.
AB  - Although phosphate phosphorus (P) is strongly sorbed in many soils, it may be
      quickly transported through the soil by preferential flow. Under flood
      irrigation, preferential flow is especially pronounced and associated solute
      losses may be important. Phosphorus losses induced by flood irrigation were
      investigated in a lysimeter study. Detailed soil chemical analyses revealed that
      P was very mobile in the topsoil, but the higher P-fixing capacity of the subsoil
      appeared to restrict P mobility. Application of a dye tracer enabled preferential
      flow pathways to be identified. Soil sampling according to dye staining patterns
      revealed that exchangeable P was significantly greater in preferential flow areas
      as compared with the unstained soil matrix. This could be partly attributed to
      the accumulation of organic carbon and P, together with enhanced leaching of Al-
      and Fe-oxides in the preferential flow areas, which resulted in reduced P
      sorption. The irrigation water caused a rapid hydrologic response by displacement
      of resident water from the subsoil. Despite the occurrence of preferential flow,
      most of the outflowing water was resident soil water and very low in P. In these
      soils the occurrence of preferential flow per se is not sufficient to cause large
      P losses even if the topsoil is rich in P. It appears that the P was retained in
      lower parts of the soil profile characterized by a very high P-fixing capacity.
      This study demonstrates the risks associated with assessing potential P losses on
      the basis of P mobility in the topsoil alone.

PMID- 11837437
TI  - Effects of conservation tillage on the performance of Lake Erie basin farms.
AB  - This paper summarizes research that investigates the effects of alternative
      farming practices on the performance of Lake Erie basin farms. First, data from a
      representative panel of about 100 farmers is analyzed to determine how
      conservation tillage, rotations, and other factors affected farms' economic
      returns during 1987-1992. Statistical analysis of these data is unable to
      demonstrate that there is any significant relationship between farming system
      (i.e., tillage and rotation) variables and farm profitability. Next, a farm-level
      bioeconomic simulation model is used to analyze the effects of conservation
      tillage adoption on farm profitability, farm size, and pollutant emissions.
      Findings are that tillage system, farm size, and crop selection are determined
      jointly and may substantially improve economic performance of farms. Conservation
      tillage enables farms to be larger and more specialized, and as a result, farm
      profitability improves. Statistical analysis of farm panel data is unable to show
      the effect of tillage on profitability because it neglects to account for
      endogeneity of variables (or joint effects of tillage, size, crop selection, and
      performance) in production decisions.

PMID- 11837438
TI  - Trace element retention and release on minerals and soil in a constructed
      wetland.
AB  - Constructed wetlands are one method under investigation for the remediation of
      trace element-contaminated agricultural drainwater. A greater understanding of
      the retention of trace elements by the bulk soil and soil constituents is
      necessary for their safe and effective use. To determine the capacity of soil,
      calcite, and goethite-coated quartz sand for retention of As, Mo, and V under
      field conditions, an in situ method was used whereby permeable bags containing
      those minerals were placed near the sediment surface of a flow-through
      constructed wetland for 3 or 12 mo. Accumulations of As, Mo, and V occurred on
      goethite-coated sand. Concentrations of Mo on goethite-coated sand were much
      higher in samples from a wetland cell with a water depth of 15 cm (38.23 +/- 7.27
      mg kg(-1)) compared with those from a cell with a water depth of 3 cm (8.30 +/-
      1.45 mg kg(-1)). Calcite sorbed no As and low amounts of Mo and V, indicating
      that it is not an important sink for those elements under these conditions. In
      soil bags, total As and V concentrations showed little change over 12 mo.
      Molybdenum accumulated in the soil bags, resulting in total concentrations (12
      mo) of 27.22 +/- 2.69 mg kg(-1) and 11.42 +/- 1.35 mg kg(-1) at water depths of
      15 and 3 cm, respectively. Nearly half of the Mo accumulation on soil became
      water soluble after air-drying. This has important implications for systems that
      may undergo changes in redox status, possibly resulting in large fluxes of water
      soluble Mo.

PMID- 11837439
TI  - Gas dynamics in eutrophic lake sediments affected by oxygen, nitrate, and
      sulfate.
AB  - In many freshwater ecosystems, the contents of NO3- and SO4(2-) have increased,
      whereas O2 has been depleted due to the increased acid and nutrient loads. These
      changes may affect carbon turnover and the dynamics of the major greenhouse gases
      CO2, CH4, and N2O. We studied the effects of O2, NO3-, and SO4(2-) availability
      on carbon mineralization, and fluxes of CO2, CH4, and N2O in the sediments of
      hyper-eutrophic Lake Kevaton, Finland. Undisturbed sediment cores from the deep
      (9 m) and shallow (4 m) profundal were incubated in a laboratory microcosm with
      oxic and anoxic water flows with NO3- or SO4(2-) concentrations of 0, 30, 100,
      300, and 2000 microM. The carbon mineralization rate (i.e., the sum of released
      CO2-C and CH4-C) was not affected by the oxidants. However, the oxidants did
      change the pathways of carbon degradation and the release of CH4. All of the
      oxidants depressed CH4 fluxes in the shallow profundal sediments, which had low
      organic matter content. In the deep profundal sediments rich in organic matter,
      the CH4 release was reduced by O2 but was not affected by SO4(2-) (the effect of
      NO3- was not studied). There was an increase in N2O release as the overlying
      water NO3- concentration increased. Anoxia and highly elevated NO3-
      concentrations, associated with eutrophication, increased drastically the global
      warming potential (GWP) of the sedimentary gases in contrast to the SO4(2-) load,
      which had only minor effects on the GWP.

PMID- 11837440
TI  - Effects of agricultural runoff on vegetation composition of a priority
      conservation wetland, Vermont, USA.
AB  - This study examined the effects of agricultural runoff on the vegetation
      structure of Franklin Bog, a priority conservation area located in a rapidly
      developing region of northwestern Vermont. Forested and agricultural runoff from
      the mixed land use watershed created differential vegetation patterns in the
      wetland, including weedy species introductions. Concentrations of nitrogen and
      phosphorus were measured in the stream runoff from four forested subwatersheds
      and two agricultural subwatersheds. Nutrient concentrations were significantly
      higher for agricultural vs. forested runoff for all measured parameters. Nitrate
      and total phosphorus concentrations in agricultural runoff ranged from 0.62 to
      1.35 mg L(-1) and 0.07 to 0.37 mg L(-1), respectively. Forested runoff values
      were less than 0.37 mg L(-1) nitrate and 0.09 mg L(-1) total phosphorus.
      Significantly higher proportions of weedy species occurred at impacted vs.
      reference sites (46 +/- 5% vs. 23 +/- 4%). Furthermore, significantly higher
      total percent vegetated cover occurred at impacted vs. reference sites (116 +/-
      11% vs. 77 +/- 9%) suggesting nutrient induced plant growth. Of the nine
      frequently occurring species categorized as bog species, only one was found
      within impacted sites while all nine were found at the reference sites. This
      suggests that the wetland's distinctive native flora is being replaced by
      widespread, vigorous species enhanced by agricultural nonpoint pollution in the
      watershed of Franklin Bog. Protection of wetlands requires attention to
      conservation measures throughout the entire watershed.

PMID- 11837441
TI  - An apparatus for measuring the gas permeability of films.
AB  - The gas permeability of plastic films is important in packaging, containment, and
      agricultural fumigation. Recently, an approach for estimating the mass transfer
      coefficient of vapors across a film was presented by Papiernik et al. (2001). The
      mass transfer coefficient is an intrinsic property of a film-chemical
      combination, independent of the concentration gradient maintained across the
      film. Here we describe an apparatus useful for obtaining permeability data; the
      model of Papiernik et al. (2001) may be fitted to the data to determine mass
      transfer coefficients. The assembled equipment provides a sealed permeability
      cell, where a sample of the film to be tested is sandwiched between two static
      half-cells. Vapor is spiked to one side of the film and the concentrations in the
      spiked and receiving chamber are monitored until equilibrium. A sealed system is
      required for this approach; the permeability cells described here were gas-tight
      for >40 d. This approach produces reproducible measures of mass transfer
      coefficients that are not dependent on the size of the experimental apparatus.
      Model parameters were similar when fitted simultaneously as when determined
      independently from the same data set.

PMID- 11837442
TI  - Relationships among plant available phosphorus, fertilizer sales, and water
      quality in northwestern Ohio.
AB  - Soluble reactive phosphorus (SRP) in northwestern Ohio river water has declined
      over the past 20 yr in response to decreased applications of fertilizer P. Our
      objective was to evaluate changes in soluble P (Bray-1 P) levels in the soil over
      time as influenced by fertilizer P management, cultivation practice, soil
      properties, and landscape factors. Because soil is the intermediary between added
      P and SRP measured in river water, we examined the relationship between
      fertilizer P, soluble soil P, and SRP. Using historical soil survey sample sites
      as a baseline for original soluble P concentrations (Por), we resampled Ap
      horizons to establish current levels of soluble P (Pcu). The Por baseline
      extended from 1953-1982 and Pcu from 1996-1998. Thirty percent of the Pcu values
      and 17% of the Por values were > or = 40 mg kg(-1). Log-transformed means for Pcu
      were significantly higher than for Por. The principal determining factors for Por
      were physiography, soil texture, and soil series. Current P is affected by
      present tillage practice and drainage class. Change in soluble P in the soil is
      not as responsive to fertilizer P sales as is SRP in river water. This suggests
      that as fertilizer P sales decline, a declining percentage of P added as
      fertilizer is annually dissolved and transported into the drainage system.
      Soluble P in soil is governed by a combination of fertilizer and tillage
      management, soil properties, and landscape factors interacting over time.

PMID- 11837443
TI  - Soils, water quality, and watershed size: interactions in the Maumee and Sandusky
      river basins of northwestern Ohio.
AB  - Soil variability in watersheds accounts for the problem of partitioning
      downstream water quality data and evaluating sources of non-point pollution. This
      review of previous water quality studies was conducted to examine more closely
      the influence of soil properties on pollutant export. The approach used in this
      paper was to start with data from the two largest watersheds (Maumee and
      Sandusky) and then compare them on a unit area export basis with data from
      intermediate-size and smaller watersheds. General relationships between pollutant
      levels at the river mouth and upstream soil conditions are vague and seemingly
      contradictory at the large-watershed scale. With smaller watersheds, it can be
      determined that soil texture, slope, and internal drainage are controlling
      factors for pollutant export. Although Paulding (very-fine, illitic, nonacid,
      mesic Typic Epiaquept) and Roselms (very-fine, illitic, mesic Aeric Epiaqualf)
      soils occupy only 5% of the Maumee basin, they generate more than 10 times as
      much sediment per unit area as the tile-drained Hoytville (fine, illitic, mesic
      Mollic Epiaqualf) soils that occupy 16% of the Maumee basin. Tile drainage of
      very poorly drained soils that are formed from either glacial till or silty to
      sandy lake deposits reduces runoff and increases downward movement of soluble
      nutrients into tile drains. The assumption that sloping moraine areas are the
      primary source of pollutants should be reexamined based on this review.

PMID- 11837444
TI  - Soil erosion and sediment sources in an Ohio watershed using beryllium-7, cesium
      137, and lead-210.
AB  - Soil cores and suspended sediments were collected within the Old Woman Creek,
      Ohio (OWC) watershed following a thunderstorm and analyzed for 7Be, 137Cs, and
      210Pb activities to compare the effects of till vs. no-till management on soil
      erosion and sediment yield. The upper reaches of the watershed draining tilled
      agricultural fields were disproportionately responsible for the majority of the
      suspended sediment load compared with lower in the watershed (2.0-7.0 metric
      tons/km2 [Mg/km2] vs. 1.2-2.6 Mg/km2). About 6 to 10 times more sediment was
      derived from the subbasins that are predominantly tilled (6.8-12.4 Mg/km2)
      compared with the subbasins undergoing no-till practices (0.5-1.1 Mg/km2). In
      undisturbed soils the 210Pb activities decreased with movement toward the bottom
      of the cores to the constant supported 210Pb value at a depth of about 10 cm.
      There was a subsurface maximum in 137Cs activity within the top 10 cm. In
      contrast, the 210Pb and 137Cs distributions in soils that are currently or were
      previously tilled were nearly homogeneous with depth, reflecting continuing or
      previous mixing by plowing. The activities of 210Pb and 7Be were linearly
      correlated and were higher in suspended sediments derived from no-till subbasins
      than those derived from tilled subbasins, indicating that the soil surface is the
      source of suspended sediment. This study demonstrates that no-till farming
      results in decreases in soil erosion and decreases in suspended sediment
      discharges and that those eroded sediments have a radionuclide signature
      corresponding to the tillage practice and the depth of erosion.

PMID- 11837445
TI  - The Lake Erie Agricultural Systems for Environmental Quality project: an
      introduction.
AB  - In the last part of the twentieth century, recognition became widespread of the
      important effect of agricultural runoff on the health of aquatic ecosystems in
      the Lake Erie basin and elsewhere. Because of the efforts to remediate Lake Erie,
      the "dead lake" among the Laurentian Great Lakes, a number of research and
      demonstration projects were undertaken in the Lake Erie basin to evaluate and
      foster adoption of conservation tillage and other farming techniques that would
      reduce runoff while maintaining productivity. In addition, intensive water
      quality studies of long duration were begun on major tributaries to Lake Erie
      during this time. The Lake Erie Agricultural Systems for Environmental Quality
      (LEASEQ) project examined governmental programs, changes in agriculture, and
      changes in water and soil quality during the period 1975-1995, and sought to
      evaluate the linkages among these factors. The study area is characterized by
      extensive agricultural land use of soils developed from glacial materials
      deposited on Paleozoic sedimentary bedrock, mostly limestone. Tile drainage is
      extensive, particularly in slow-draining clay-rich lacustrine soils in the lower
      reaches of the watersheds. This paper introduces the study area, its geology,
      geography, soils, and agricultural history. In addition, we provide an overview
      of the LEASEQ concept and introduce the 11 other papers in this series, which
      provide a detailed exposition of the results of our studies.

PMID- 11837446
TI  - Radionuclides as indicators of sediment transport in agricultural watersheds that
      drain to Lake Erie.
AB  - An issue in evaluating the success of agricultural management practices is the
      speed that eroded particles make their way through the downstream waters. In this
      study at Old Woman Creek (OWC) and Rock Creek (RC), two largely agricultural
      watersheds in Ohio, the flux of sediment and radionuclides (7Be, 210Pb, and
      137Cs) in thunderstorm runoff was examined to better understand transport of
      eroded agricultural soils. The hydrograph in an agricultural area under no-till
      was similar in timing, but of lesser magnitude, than the hydrograph from a
      similar-sized area under conventional tillage. The activities of 210Pb and 7Be
      are linearly correlated and are higher in suspended sediments derived from no
      till subbasins than those derived from conventionally tilled subbasins. A
      suspended sediment plume, identified by its unique radionuclide signature, was
      traced through 17 km of OWC stream channel in approximately 13.4 h (0.35 m/s).
      The downstream exponential decrease of 7Be activities in suspended sediments 3 to
      12 h after passage of the sediment plume was used to estimate transport distances
      of suspended sediment from 2 to 17 km, respectively. Transport distances of
      suspended sediments were also calculated from wave kinematics and indicate that
      at OWC suspended sediment transport distances were longer in streams draining
      areas of no-till (19-26 km) than in the streams draining areas of conventional
      tillage (6-15 km). Suspended sediments travel 7 to 22 km at RC. The transport
      distances are long relative to the lengths of the stream channel and indicate
      that erosion control methods implemented in the watershed should be reflected
      quickly in downstream waters.

PMID- 11837447
TI  - Climatic and agricultural factors in nutrient exports from two watersheds in
      Ohio.
AB  - Export of agricultural nutrients and sediment to lakes and oceans is of great
      environmental concern in many agricultural watersheds. Recent years have seen
      efforts to reduce loads through agricultural practices such as conservation
      tillage, efficient fertilization, and reservation of erodible areas. Monitoring
      the efficacy of such efforts is complicated by the fact they take place against a
      varying climatic and hydrologic background. In this study, statistical analysis
      was used to identify those climatic, hydrologic, and agricultural variables that
      best explained variations in nitrate, phosphorus, and total suspended solids over
      the period 1976-1995 in two large agricultural watersheds that feed Lake Erie,
      those of the Maumee and Sandusky Rivers. The dominant variable was stream
      discharge; after curvefits to remove its influence, the residual loads were
      tested via stepwise linear regression to reveal the most significant explanatory
      variables. Loads of nitrate, total suspended solids, and total phosphorus tended
      to decrease when previous months were wet, except in the summer, and to decrease
      when snow cover was extensive. It is speculated that stores of nitrate in the
      soil were lost during wet periods through increased crop uptake and/or leaching.
      Nitrogen fertilizer application in the Maumee watershed decreased following dry
      periods, but not enough to decrease stream loads. Soluble reactive phosphorus
      loads were negatively correlated to conservation tillage and reserves, and
      positively correlated to fertilizer and manure sources. Results for total
      phosphorus were similar to those for total suspended solids, on which most
      transported phosphorus is adsorbed.

PMID- 11837448
TI  - Climatic and agricultural contributions to changing loads in two watersheds in
      Ohio.
AB  - Trends in climatic variables, streamflow, agricultural practices, and loads of
      nutrients and suspended solids were estimated for 1976-1995 in the Maumee and
      Sandusky watersheds, two large agricultural basins draining to Lake Erie. To
      understand the contributions that various factors may have made to the trends in
      loads, earlier results of models linking loads to explanatory variables were
      combined with estimated trends in those variables. The study period was
      characterized by increases in temperature, wintertime precipitation and
      streamflow, conservation farming, and loads of nitrate and total suspended
      solids; decreases in snowfall and snow cover, fertilizer, manure from livestock,
      and loads of soluble reactive phosphorus; and relatively steady exports of total
      phosphorus. After removing the effects of trends in streamflow, nitrate loads
      increased much less while total suspended solids and total phosphorus loads
      declined. The analysis suggests that the nitrate increases were due largely to
      climatic factors, particularly increases in winter streamflow, decreases in
      snowfall and snow cover, and declining annual precipitation. Decreases in soluble
      reactive phosphorus were associated with changes in agricultural practices,
      particularly declines in fertilizer deliveries and head of livestock.

PMID- 11837449
TI  - Trends in water quality in LEASEQ rivers and streams (northwestern Ohio), 1975
      1995. Lake Erie Agricultural Systems for Environmental Quality.
AB  - Trends in water quality in four northwest Ohio rivers over the period 1975-1995
      were identified using datasets of daily concentrations containing 4500 to 6800
      observations per river during the study period. Concentrations were log
      transformed prior to analysis, and adjusted for flow using a locally weighted
      scatterplot smoother (LOWESS) fit between log(concentration) and log(flow).
      Seasonality was modeled using one- and two-cycle sinusoidal oscillations and
      monthly additive constants. Substantial decreases in total and soluble reactive
      phosphorus were documented at all stations. Smaller but highly significant
      decreases in total Kjeldahl nitrogen were documented at all stations, and
      significant decreases in total suspended solids were documented at three of the
      four stations. Nitrate did not show significant trends at the two stations
      draining major watersheds, and showed significant trends in opposite directions
      at the two stations on smaller watersheds. Comparisons using nonparametric,
      nonlinear trend fits (LOWESS) suggest that changes in fertilizer and manure
      application rates are the most important cause of trends in phosphorus and total
      Kjeldahl nitrogen; point sources are insufficient to account for the phosphorus
      trends. The conflicting trends for nitrate are enigmatic, but may reflect
      diverging land use in the two smaller watersheds.

PMID- 11837450
TI  - Phosphorus budgets and riverine phosphorus export in northwestern Ohio
      watersheds.
AB  - Phosphorus (P) budgets for large watersheds are often used to predict trends in
      riverine P export. To test such predictions, we calculated annual P budgets for
      1975-1995 for soils of the Maumee and Sandusky watersheds of northwestern Ohio
      and compared them with riverine P export from these watersheds. Phosphorus inputs
      to the soils include fertilizers, manure, rainfall, and sludge while outputs
      include crop removal and nonpoint-source export via rivers. Annual P inputs
      decreased due to reductions in fertilizer and manure inputs. Annual outputs
      increased due to increasing crop yields. Net P accumulation decreased from peak
      values of 13.4 and 9.5 kg P ha(-1) yr(-1) to 3.7 and 2.6 kg P ha(-1) yr(-1) for
      the Maumee and Sandusky watersheds, respectively. Thus, P budget analysis
      suggests that riverine P export should have increased throughout the study
      period, with smaller increases during more recent years. However, detailed water
      quality studies show that riverine export of total phosphorus (TP) has decreased
      by 25 to 40% and soluble reactive phosphorus (SRP) by 60 to 89%, both due
      primarily to decreases from nonpoint sources. We suggest that these decreases are
      associated with farmers' adoption of practices that minimize transport of
      recently applied P fertilizer and of sediments via surface runoff, coupled with
      changes in winter weather conditions. In comparison with most Midwestern
      watersheds, rivers draining these watersheds have high unit area yields of TP,
      low unit area yields of SRP, and high ratios of nonpoint source- to point source
      derived P.

PMID- 11837451
TI  - Agouti: from mouse to man, from skin to fat.
AB  - The agouti protein regulates pigmentation in the mouse hair follicle producing a
      black hair with a subapical yellow band. Its effect on pigmentation is achieved
      by antagonizing the binding of alpha-melanocyte stimulating hormone (alpha-MSH)
      to melanocortin 1 receptor (Mc1r), switching melanin synthesis from eumelanin
      (black/brown) to phaeomelanin (red/yellow). Dominant mutations in the non-coding
      region of mouse agouti cause yellow coat colour and ectopic expression also
      results in obesity, type 11 diabetes, increased somatic growth and
      tumourigenesis. At least some of these pleiotropic effects can be explained by
      antagonism of other members of the melanocortin receptor family by agouti
      protein. The yellow coat colour is the result of agouti chronically antagonizing
      the binding of alpha-MSH to Mc1r and the obese phenotype results from agouti
      protein antagonizing the binding of alpha-MSH to Mc3r and/or Mc4r. Despite the
      existence of a highly homologous agouti protein in humans, agouti signal protein
      (ASIP), its role has yet to be defined. However it is known that human ASIP is
      expressed at highest levels in adipose tissue where it may antagonize one of the
      melanocortin receptors. The conserved nature of the agouti protein combined with
      the diverse phenotypic effects of agouti mutations in mouse and the different
      expression patterns of human and mouse agouti, suggest ASIP may play a role in
      human energy homeostasis and possibly human pigmentation.

PMID- 11837453
TI  - Analysis of xanthophore and pterinosome biogenesis in zebrafish using methylene
      blue and pteridine autofluorescence.
AB  - We have identified two simple methods to analyse xanthophore and pterinosome
      biogenesis in zebrafish. The first uses methylene blue (methylthionium chloride),
      a redox dye which specifically labels xanthophores and pterinosomes, while the
      second uses autofluorescence to detect pteridine levels; these methods may be
      used to detect the number, location and shape of xanthophores and pterinosomes.
      These assays were applied to two zebrafish mutants--brie and yobo--and revealed
      that both mutants have pterinosome biogenesis and pteridine synthesis defects.
      Additionally, using capillary electrophoresis, we provide evidence that
      sepiapterin is responsible for the yellow colour and blue-light induced
      fluorescence in zebrafish embryos.

PMID- 11837452
TI  - Comparative biochemistry of eumelanogenesis and the protective roles of
      phenoloxidase and melanin in insects.
AB  - The phenolic biopolymer eumelanin is an important skin pigment found throughout
      the animal kingdom. The enzyme, tyrosinase, initiates melanogenesis in mammals.
      The biogenesis is assisted by a number of mammalian protein factors including
      dopachrome tautomerase and 5,6-dihydroxyindole-2-carboxylate oxidase.
      Invertebrates, such as insects, employ phenoloxidase and dopachrome
      (decarboxylating) isomerase for melanin biosynthesis. Recently generated
      molecular biological and biochemical data indicate that tyrosinase and
      phenoloxidase are distinctly different enzymes in spite of possessing both
      monophenol monooxygenase activity as well as o-diphenoloxidase activity.
      Similarly, insect dopachrome isomerase also differs significantly from its
      mammalian counterpart in several of its properties including the nature of the
      enzymatic reaction. In addition, there are considerable differences in the
      eumelanogenic pathways of these two animal groups that include the utility of
      substrates, use of dihydroxyindoles and the nature of eumelanin pigment. Thus,
      the biochemistry and molecular biology of melanogenesis in mammals and insects
      are significantly different. The advantages of generating different eumelanin
      pigments and intermediates by the insects are discussed.

PMID- 11837454
TI  - Spleen and liver pigmented macrophages of Rana esculenta L. A new melanogenic
      system?
AB  - The present study reports the results of a morpho-functional analysis of spleen
      pigmented cells from Rana esculenta L. and comparison with liver melanin
      synthesizing cells, belonging to the macrophage cell lineage. Cytological and
      cytochemical analyses show that parenchymal pigmented cells of the spleen, like
      those of the liver, are positive to peroxidase and lipase reactions and have
      phagocytic properties. The observation of premelanosomes in various stages of
      differentiation, together with the demonstration of dopa oxidase activity in the
      melanosome proteins, indicate that spleen pigmented macrophages have endogenous
      melanogenic ability as do liver pigmented macrophages. Attempts to demonstrate
      tyrosinehydroxylase activity in melanosome protein extracts from frog spleen and
      liver, using the same protocol as for mammalian tyrosinases, gave negative
      results. As regards the dopa oxidase activity revealed, some of its properties
      differ from the typical behaviour observed for tyrosinases from different
      sources. Peroxidase activity is shown in spleen and liver melanosome proteins
      with p-phenylenediamine-pyrocatechol (PPD-PC), and not with typical peroxidase
      substrates. Suitable inhibition tests revealed that dopa oxidase and peroxidase
      activities might be supported by two different proteins. Liver melanosome
      extracts display a very strong laccase (dimethoxyphenoloxidase) activity but
      spleen extracts do not. Differences observed in the enzymatic properties of the
      spleen and liver melanosomes suggest that pigmented macrophages may undergo
      tissue-specific differentiation. These preliminary data show that the melanin
      pathway of pigmented macrophages is different from that of melanocytes and may
      pave the way to identification of a new melanogenic pathway in vertebrates.

PMID- 11837455
TI  - Dermal nevus cells from congenital nevi cannot penetrate the dermis in skin
      reconstructs.
AB  - Congenital nevi are composed of pigment cells bearing common features with
      melanocytes but showing altered differentiation which leads to nesting and dermal
      involvement. Using a dead de-epidermized dermis seeded with a combination of
      keratinocytes and various sources of pigment cells (normal melanocytes, dermal
      nevus cells from congenital nevi, Bowes melanoma cells), we have studied the
      formation of nests and the dermal migration of pigment cells together with their
      secretion profiles of matrix metalloproteinases (MMP). Dermal fibroblasts were
      also used as control cells in epidermal reconstructs. Besides their morphologic
      features, the absence of pigment donation to keratinocytes was the major
      characteristic of dermal nevus cells. A positive correlation was established
      between the increasing percentage of seeded nevus cells and the patchy
      pigmentation of reconstructs, as well as the clustering of cells in junctional
      nests. However, the presence of nevus cells in the dermis of reconstructs was
      never detected, whereas melanoma cells and dermal fibroblasts could invade the
      dermis during the time span of the experiments. MMP9 was never expressed in
      congenital dermal nevus cells but pro-MMP2 was constitutively expressed by all
      strains of congenital nevus cells and dermal fibroblasts. Melanocytes produced
      comparable amounts of both pro-MMP2 and pro-MMP9, and Bowes melanoma cells
      secreted a marginal level of pro-MMP2. In view of their three-dimensional
      behaviour and secretion of MMPs, we propose that dermal congenital nevus cells
      correspond to an intermediate status of differentiation between normal
      melanocytes and melanoma cells. Activation of MMPs by a cofactor or the
      activation of another signalling pathway seems necessary to induce the dermal
      passage of nevus cells.

PMID- 11837456
TI  - Fibroblasts play a regulatory role in the control of pigmentation in
      reconstructed human skin from skin types I and II.
AB  - Human melanocytes in monolayer culture are extremely dependent on a wide range of
      soluble signals for their proliferation and melanogenesis. The advent of three
      dimensional models of reconstructed skin allows one to ask questions of how these
      cells are regulated within a setting which more closely approximates normal skin.
      The purpose of this study was to investigate to what extent melanocytes within a
      reconstructed skin model are sensitive to regulation by dermal fibroblasts,
      basement membrane (BM) proteins and the addition of alpha-melanocyte-stimulating
      hormone (alpha-MSH). Sterilized acellular de-epidermized dermis (prepared to
      retain BM proteins or deliberately denuded of BM by enzymatic treatment) from
      skin type I or II was reconstituted with fibroblasts, melanocytes and
      keratinocytes. In all but one case (9/10), cell donors were skin type I or II.
      The presence of BM antigens was found to be necessary for positional orientation
      of the melanocytes; in the absence of BM, melanocytes moved into the upper
      keratinocyte layer pigmenting spontaneously. Addition of fibroblasts suppressed
      the extent of spontaneous pigmentation of melanocytes within this model. Neither
      alpha-MSH nor cholera toxin induced pigmentation in this model despite the fact
      that melanocytes clearly had the ability to synthesize pigment.

PMID- 11837457
TI  - Melanophore appearance in wild and red tilapia embryos.
AB  - Red tilapia has aroused interest in many countries for its commercial potential.
      This tilapia strain combines a desirable coloration and appearance with other
      advantageous farming characteristics. To study the early appearance of
      melanophore pigmentation in tilapia, a red tilapia strain originating from
      Thailand and a wild type coloration of Oreochromis niloticus were used as
      broodstock to produce artificially wild x wild and red x red progenies. The
      larvae were assessed periodically up to the first feeding and were recorded. Wild
      type fish showed a regular appearance of stellate melanophores. In the red
      strain, the pattern of chromatophores varies from total absence of black spotting
      to different degrees of macromelanophore distribution. Comparison between red and
      wild types showed that these two tilapia can be easily scored at day 7. Further,
      we present indications that the pigmentation over the body develops independently
      of the initial degree of pigmentation.

PMID- 11837458
TI  - Genetic association of the catalase gene (CAT) with vitiligo susceptibility.
AB  - Vitiligo susceptibility is a complex genetic trait that may involve genes
      important for melanin biosynthesis, response to oxidative stress, and/or
      regulation of autoimmunity, as well as environmental factors. We report here case
      control and family-based association studies for the catalase gene (CAT) in
      vitiligo patients. The CAT gene was selected as a candidate gene because of the
      reduction of catalase enzyme activity (EC 1.11.1.6) and concomitant accumulation
      of excess hydrogen peroxide observed in the entire epidermis of vitiligo
      patients. One of three CAT genetic markers studied was found to be informative
      for genotypic analysis of Caucasian vitiligo patients and control subjects. Both
      case/control and family-based genetic association studies of the T/C single
      nucleotide polymorphism (SNP) in exon 9 of the CAT gene, which is detectable with
      the restriction endonuclease BstX I, suggest possible association between the CAT
      gene and vitiligo susceptibility. The observations that T/C heterozygotes are
      more frequent among vitiligo patients than controls and that the C allele is
      transmitted more frequently to patients than controls suggest that linked
      mutations in or near the CAT gene might contribute to a quantitative deficiency
      of catalase activity in the epidermis and the accumulation of excess hydrogen
      peroxide (H2O2). The CAT gene may, therefore, be a susceptibility gene in some
      vitiligo patients, further supporting the epidermal oxidative stress model for
      vitiligo pathogenesis.

PMID- 11837459
TI  - Effect of boron neutron capture therapy for melanotic and amelanotic melanoma
      transplanted into mouse brain.
AB  - In order to develop a protocol to treat brain metastatic melanoma using our 10B-p
      boronophenylalanine (BPA) boron neutron capture therapy (BNCT), we initiated the
      following studies (i), Comparative analyses of boron biodistribution between
      melanoma proliferating in the brain and skin among melanotic and amelanotic
      types, and (ii) Therapeutic evaluation of BPA-BNCT for brain melanoma models of
      both types, using survival times. Our present data have revealed that boron
      concentration in melanoma proliferating in the brain, the major prerequisite for
      successful BNCT, showed a positive correlation to melanin synthesizing activity
      in the same way as melanoma proliferating in skin. Further, the boron
      concentration ratio of melanoma to normal surrounding tissue for brain melanoma
      models was considerably higher than that for subcutaneous (s.c.) ones because of
      the existence of the blood-brain barrier (BBB). Additionally, from analyses of
      median and mean survival times following BNCT using low, middle, and high neutron
      doses, the therapeutic effect of BNCT for the amelanotic A1059 melanoma appeared
      at first glance to be higher than that for the highly BPA attracting and highly
      relative biological effect equivalent dose obtaining B15b melanoma. As the
      survival time was dependent on both regression and regrowth curves, and because
      the brain melanoma model in small animals made it difficult to evaluate these
      curves separately, we further examined the in vivo growth curve of both types of
      melanomas following implantation in s.c. tissue. The melanotic B15b melanoma was
      indeed found to possess much higher growth rate as compared with that of the
      amelanotic A1059 melanoma. The significance of boron biodistribution studies and
      BNCT survival curve analyses in forming an effective clinical protocol for
      individual human cases of melanoma brain metastasis is discussed.

PMID- 11837460
TI  - Male mental health problems, psychopathy, and personality traits: key findings
      from the first 14 years of the Pittsburgh Youth Study.
AB  - This paper reviews key findings on juvenile mental health problems in boys,
      psychopathy, and personality traits, obtained in the first 14 years of studies
      using data from the Pittsburgh Youth Study. This is a study of 3 samples, each of
      about 500 boys initially randomly drawn from boys in the 1st, 4th, and 7th grades
      of public schools in Pittsburgh. The boys have been followed regularly, initially
      each half year, and later at yearly intervals. Currently, the oldest boys are
      about 25 years old, whereas the youngest boys are about 19. Findings are
      presented on the prevalence and interrelation of disruptive behaviors, ADHD, and
      depressed mood. Results concerning risk factors for these outcomes are reviewed.
      Psychological factors such as psychopathy, impulsivity, and personality are
      described. The paper closes with findings on service delivery of boys with mental
      health problems.

PMID- 11837461
TI  - Treating childhood shyness and related behavior: empirically evaluated approaches
      to promote positive social interactions.
AB  - Behavioral and cognitive-behavioral strategies, including exposure, social skills
      training, and peer-mediated approaches, used to treat childhood shyness and
      related impairments are described. In addition, relevant outcome studies
      published within the past 20 years are evaluated, and limitations regarding the
      generalization, maintenance, and social validity of the reported treatment gains
      are addressed. Although the interventions reviewed have demonstrated short-term
      merit in ameliorating social and emotional impairments, such as problematic peer
      relations and internalizing difficulties, there currently is a lack of evidence
      to support the social validity and long-term generalization and maintenance of
      such behavioral gains. Thus, recommendations for future research are made,
      including the need to (a) assess the social validity of treatment outcomes, (b)
      utilize important socialization agents (e.g., parents, teachers, peers), and (c)
      conduct prevention research and longitudinal outcome studies.

PMID- 11837463
TI  - Hairy cell leukaemia--therapeutic options.

PMID- 11837462
TI  - Influences of marital conflict on child adjustment: review of theory and
      research.
AB  - This review summarizes the literature on the relationship between marital
      conflict and child maladjustment with an emphasis on variables that qualify,
      explain the association, or both. Following a historical review, the modest
      findings on the strength of the association between marital conflict and child
      maladjustment is explored. The definition of marital conflict is clarified
      through specification of its various dimensions (frequency, intensity, content,
      resolution). The role of variables that serve to moderate and/or mediate the
      relationship between marital conflict and child maladjustment are elaborated.
      Mediating models include exposure theories (Modeling, Cognitive-Contextual
      effects: appraisal of threat and blame, and Emotional Insecurity) and changes in
      the parent-child relationship (Spillover). Variables that moderate or qualify the
      relationship include children's cognitions and behaviors, contextual factors, and
      demographic differences. A model is presented summarizing these mechanisms.
      Research recommendations are proposed and the clinical implications of this
      literature are addressed.

PMID- 11837464
TI  - 2-CdA in the treatment of hairy cell leukaemia.
AB  - INTRODUCTION: Hairy cell leukaemia (HCL) is a rare lymphoproliferative disorder.
      Treatment options available are splenectomy, interferon, DCF and 2-CdA. 2-CdA is
      considered to have curative potential as proved by the other studies. METHODS: We
      gave 2-CdA in a dose of 0.09/kg/day as a continuous infusion in sixteen patients
      of hairy cell leukaemia. RESULTS: Three patients developed neutropenia post
      transfusion. At the end of three months all patients were in remission. Two
      patients relapsed at the median follow-up of 15 months. CONCLUSION: 2-CdA in HCL
      can achieve complete remission, prolonged survival and care as well.

PMID- 11837465
TI  - Significance of haematological manifestations in patients with tuberculosis.
AB  - OBJECTIVE: Tuberculosis is a major public health problem in India. Haematological
      changes associated with tuberculosis have been incompletely investigated. To the
      best of our knowledge, there is no comprehensive study assessing the
      haematological abnormalities in these patients from the Indian subcontinent. In
      the present study, we have compared peripheral blood and bone marrow findings in
      patients with disseminated/miliary tuberculosis (DTB/MTB) as well as pulmonary
      tuberculosis (PTB). An attempt has also been made to assess the effect of
      antituberculosis therapy on the haematologic abnormalities. MATERIAL AND METHODS:
      Thirty two patients with disseminated/miliary tuberculosis and 23 patients with
      pulmonary tuberculosis were prospectively studied to determine the various
      haematological manifestations in tuberculosis and the effect of antituberculosis
      therapy. All patients received standard antituberculosis treatment. They were
      subjected to a detailed haemogram including peripheral blood examination, which
      was repeated on completion of antituberculosis therapy. Bone marrow aspiration
      and biopsy was also done in all patients before starting antituberculosis
      treatment. RESULTS: Normocytic normochromic anaemia was the most common
      abnormality observed in all the groups and subgroups (DTB/MTB 84%, PTB 86%).
      Other haematological abnormalities of the white blood cells include leucopenia
      (DTB/MTB 25%, PTB 0%; p < 0.02), neutropenia (DTB/MTB 22%, PTB 0%; p < 0.04),
      lymphocytopenia, monocytopenia, leukocytosis, neutrophilia, lymphocytosis and
      monocytosis. Pancytopenia was observed only in patients with disseminated/miliary
      tuberculosis (p < 0.05). Thrombocytopenia was more common in patients with
      disseminated/miliary tuberculosis (p < 0.007), whereas thrombocytosis was more
      common in patients with pulmonary tuberculosis (p < 0.04). The patients of
      disseminated/miliary tuberculosis with granulomas in the bone marrow had certain
      significant differences as compared to patients without granulomas. These
      patients showed severe anaemia, peripheral monocytopenia and bone marrow
      histiomonocytosis. The haemogram reverted to normal with antituberculosis therapy
      in these patients. CONCLUSIONS: In view of the varied haematological
      abnormalities observed in patients with tuberculosis in this part of the world,
      it is concluded that the differential diagnosis of tuberculosis should be
      entertained in patients with varied haematological disorders.

PMID- 11837466
TI  - Calcium supplementation in pre-eclampsia.
AB  - OBJECTIVE: The objective of this prospective, open, randomised trial was to
      determine the role of calcium supplementation in preventing pre-eclampsia.
      METHODS: One hundred uncomplicated normotensive primigravidae were enrolled in
      the study before 20 weeks of pregnancy. Fifty each were randomised to receive
      either two gram elemental calcium daily from 20 weeks of gestation to delivery
      (study group) or no calcium supplementation (control group). Prior to 20 weeks of
      gestation each underwent a complete clinical and laboratory evaluation. Serum and
      urine calcium was measured first at 20 weeks of gestation and then at 24-28 weeks
      and at 32-36 weeks of pregnancy. RESULTS: Patient characteristics at the start of
      therapy were similar in the two groups. Blood pressure profile was similar
      throughout pregnancy in the groups. The incidence of pre-eclampsia was similar
      (18% in the study group and 16% in the control group), but severe pre-eclampsia
      was significantly less in the study group. There was no significant difference
      between the two groups with regards to intra- and postpartum characteristics,
      perinatal outcome and maternal or fetal side effects. Serum and urinary calcium
      levels did not differ between the two groups. CONCLUSION: While calcium
      supplementation did not lower the incidence of pre-eclampsia it did reduce its
      severity.

PMID- 11837467
TI  - Cytokine profile in human immunodeficiency virus positive patients with and
      without tuberculosis.
AB  - BACKGROUND: Human immunodeficiency virus (HIV) infection is associated with a
      profound dysregulation of the immune system and alterations in the cytokine
      profile. Tuberculosis, a common opportunistic infection in HIV positive patients,
      leads to further immune suppression and a faster progression of the disease. This
      study was conducted to assess and compare the cytokine profiles in HIV positive
      subjects with and without pulmonary tuberculosis. METHODS: Twenty HIV positive
      patients and 20 controls were evaluated after being divided into four groups of
      10 each--group 1--HIV positive patients without tuberculosis, group 2--HIV
      positive patients with pulmonary tuberculosis, group 3--healthy adults and group
      4--HIV negative patients with pulmonary tuberculosis. After clinical evaluation,
      the CD4 cell counts and the cytokine profiles--interleukins (IL)-2, 4, 6, 10, 12,
      interferon gamma (IFN gamma) and tumour necrosis factor alpha (TNF alpha) were
      studied in all the subjects at the start and after three months of
      antituberculosis therapy. RESULTS: the CD4 cell counts were significantly lower
      in groups 1 and 2 compared to groups 3 (p < 0.01) and the counts in group 2 were
      significantly lower than in group 1 in both at baseline (p = 0.0076) and at three
      months (p = 0.089). The levels of the type 1 cytokines (IL-2, IL-12 and IFN gamma
      were significantly lower in patients in groups 1 and 2 compared to group 3 (p <
      0.001 for both). The levels in group 2 were lower than in group 1 (p < 0.001).
      The type 2 cytokines (IL-4, IL-6, IL-10 and TNF alpha) were higher in group 1 and
      2 compared to group 3, though statistically significant for IL-6 in group 1 (p <
      0.05) and for IL-4, IL-6 and TNF alpha in group 2. A highly significant (p <
      0.0001) positive correlation between CD4 cell counts and type 1 cytokines and a
      highly significant (p < 0.0001) negative correlation between CD4 cell counts and
      type 2 cytokines was observed. CONCLUSIONS: A decline in the type 1 and a rise in
      type 2 cytokines was observed in HIV infection. Patients in group 2 had the
      lowest CD4 cell counts, lowest levels of type 1 cytokines and highest levels of
      type 2 cytokines denoting maximum immunosuppression.

PMID- 11837468
TI  - Glibenclamide vs gliclazide in reducing oxidative stress in patients of
      noninsulin dependent diabetes mellitus--a double blind randomized study.
AB  - OBJECTIVE: Parameters of oxidative stress were quantitated in 50 patients with
      type 2 diabetes mellitus in uncontrolled state and after control using oral
      glibenclamide or gliclazide. The estimates were further compared between the two
      groups irrespective of drug used to evaluate the difference, if any. METHODS: The
      study was a double blind, uncontrolled, noncrossover and randomized trial. Fifty
      patients of uncontrolled type 2 diabetes were divided in to two groups. Group I
      (25 patients) received capsule A (glibenclamide) while Group II (25 patients)
      received capsule B (gliclazide). The parameters studied were Superoxide dismutase
      (SOD), malonyl-dialdehyde (MDA) and reduced glutathione (GSH). They were done at
      (a) uncontrolled stage (FBS--165 +/- 16.7 mg/dl, PP--240 +/- 30.1 mg/dl and HbA1-
      10.5 +/- 0.9% in group I and FBS--150 +/- 15.8 mg/dl, PP--246 +/- 29.1 mg/dl HbA1
      10.6 +/- 0.8% in group II) and during controlled stage at 12 weeks (FBS--120 +/-
      18.5 mg/dl, PP--180 +/- 19.1 mg/dl and HbA1--8.4 +/- 0.29% in group I and FBS-
      118 +/- 17.6 mg/dl, PP--176 +/- 20.1 mg/dl and HbA1--8.5 +/- 0.39% in group II
      patients). RESULTS: The significantly raised levels of MDA and SOD, and decreased
      levels of reduced glutathione (GSH) during uncontrolled stage of diabetes
      indicated free radical stress induced lipid peroxidation. The significant fall of
      MDA and SOD and increased levels of GSH in blood in both groups after control
      revealed beneficial effects of glycemic control on oxidative stress. The levels
      were not normalized and stayed higher than those in controls. On intergroup
      comparison; the control of diabetes with gliclazide (group II) showed improvement
      in oxidative stress (MDA, GSH) better (p < 0.001) than glibenclamide (group I).
      CONCLUSION: Oxidative stress in uncontrolled diabetes is decreased with glycemic
      control. The control of diabetes with gliclazide reduced oxidative stress more
      than glibenclamide, indicating higher antioxidant properties of gliclazide.
      Normalization of oxidative stress was not achieved. Further studies are required
      to see long-term effect of drug therapy in combating oxidative stress after
      achieving acceptable control of diabetes.

PMID- 11837469
TI  - A clinico-bacteriological study of peripheral tuberculous lymphadenitis.
AB  - OBJECTIVE: Tuberculous lymphadenitis is the commonest form of extra-pulmonary
      tuberculosis. It is most often caused by M. tuberculosis though several reports
      from other countries have shown mycobacteria other than tuberculosis (MOTT) to be
      responsible for a significant proportion of tuberculous lymphadenitis cases. The
      present study was conducted to find the prevalence of M. tuberculosis and MOTT as
      aetiological agents in patients with peripheral tuberculous lymphadenitis.
      METHODS: A total of 138 patients with tuberculous lymphadenitis were included in
      the study. Diagnosis of tuberculosis was established on the basis of fine needle
      aspiration cytology, histopathology, presence of mycobacteria on Ziehl Neelson
      stain or auramine rhodamine stain, or aspiration of pus with negative Gram's
      stain and pyogenic cultute with radiologic evidence of pulmonary tuberculosis.
      Mycobacterial cultures were performed on aspirated material and species
      identified using standard methods. RESULTS: Of 138 patients, single lymph nodal
      enlargement was found in 48.6% patients while others had more than one lymph
      nodes. Lymph nodes were matted in 26.8% cases while fluctuation could be elicited
      in 12.3% patients. Chest X-ray showed evidence of active pulmonary lesions or
      mediastinal lymphadenopathy in 28.3% cases. The fine needle aspiration cytology
      was positive for tuberculous lymphadenitis in 41.3% cases while it revealed
      granulomas or necrosis in another 13% cases. The Ziehl-Neelson and the auramine
      rhodamine staining were positive in 19.6% and 26.8% patients, respectively. On
      culture, the lymph node aspirate was positive for Mycobacterium species in 40.6%
      patients. In all but two cases, the culture revealed presence of Mycobacterium
      tuberculosis. The other two cultures revealed growth of Mycobacterium fortuitum
      chelonae complex. Of the two HIV-positive patients, M. tuberculosis could be
      isolated in one case. CONCLUSION: Findings of this study suggest that M.
      tuberculosis is still the most common cause of tuberculous lymphadenitis and MOTT
      are responsible for very few cases. However, such studies need to be carried out
      frequently at various centres so as to see any periodic and geographic variations
      within India.

PMID- 11837470
TI  - Human immunodeficiency virus-associated nephropathy.
AB  - Human immunodeficiency virus-associated nephropathy (HIVAN) is a
      clinicopathological entity characterised by proteinuria, rapidly developing
      azotemia and histologically by collapsig variant of focal and segmental
      glomerulosclerosis with acute tubular necrosis and mild interstitial
      inflammation. Untreated, it may result in end stage renal disease (ESRD) in as
      little as four months. The incidence of HIVAN continues to increase and is the
      single most common cause of chronic renal disease in HIV-1 seropositive patients.
      It affects predominantly black individuals. Exact pathogenesis is still not clear
      but a great deal of progress has been made in the recent past by studies on
      transgenic mouse model, renal cell cultures and from study of human biopsy
      material. Current considerations revolve around the role of HIV or protein in
      renal epithelium and the effects of cytokines, including transforming growth
      factor-beta and basic fibroblast growth factor on renal structures. Different
      modalities of treatment with corticosteroids, zidovudine or angiotensin
      converting enzyme inhibitors have been tried with modest success.

PMID- 11837471
TI  - Lord Dhanvantari (Vedic Period). Postal Stamp of Nepal 1977.

PMID- 11837472
TI  - Pictorial CME. Familial hypercholesterolaemia with tendinous xanthomas and
      xanthomatous aortic stenosis.

PMID- 11837473
TI  - Physician assisted suicide--the perspective of a neurologist.
AB  - Modern medicine has resulted in a better control and treatment of many diseases.
      This has provided a better life for patients with treatable disorders, but at the
      same times has prolonged the suffering of the patients with diseases that are not
      treatable. This is of particular importance for the patients with neurological
      diseases, as some of these conditions have a relentlessly progressive course and
      cause significant distress to the patient. Recent times have seen an expansion of
      the scope of the various "rights of the patient" and according to some, this
      includes the "right to die". As a result of this concept of regarding the
      autonomy of the patient, the phenomenon of physician assisted suicide has emerged
      and is a topic of intense debate amongst the physicians, social workers and
      politicians all over the world. The present article puts forth the current
      concepts and brings out the exact definitions of the terms like physician
      assisted suicide, voluntary active euthanasia and voluntary passive euthanasia.
      It presents the statements made by the various societies and organisations
      regarding the PAS. It also brings forth the point of view of the authors about
      this aspect of medicine. The authors share the view of the various scientific
      organisations, and opine that though the idea of physician assisted suicide may
      be morally justifiable in certain circumstances, it should not be made legal.

PMID- 11837474
TI  - Safety and efficacy of moxonidine in mild to moderate hypertension.
AB  - AIMS: Moxonidine, a new imidazoline II receptor agonist was evaluated in patients
      with essential hypertension. METHODOLOGY: After an informed consent, 16 patients
      with essential hypertension were recruited. After a wash out period, the patients
      received increasing doses of Moxonidine (maximum dose 0.6 mg) for four weeks to
      control the blood pressure. RESULTS: The mean reduction in blood pressure
      (systolic/diastolic) was 17.6/14.5 mm Hg in supine position and 18.2/12.6 mm Hg
      in standing position. The significant side effect was observed only in one
      patient. CONCLUSIONS: Moxonidine thus appears to be safe and effective
      antihypertensive drug in patients with essential hypertension.

PMID- 11837475
TI  - Is academic medicine for sale?

PMID- 11837476
TI  - Renal failure in a case of histoplasmosis.

PMID- 11837477
TI  - Co-existing spinal cord and brain cavernous angiomas.
AB  - Cavernous angioma of spinal cord is an extremely rare vascular malformation. The
      association with brain cavernous angioma is even uncommon. There should be a high
      index of suspicion for a spinal cord lesion whenever a brain cavernous angioma is
      diagnosed, in cases with appropriate suggestive spinal symptoms. We present a
      case of cavernous angioma of the brain involving the genu of the corpus callosum,
      co-existing with spinal cord hemangioma. Involvement of the corpus callosum by a
      cavernous angioma is also uncommon. Intraventricular extension of this lesion was
      also detected.

PMID- 11837478
TI  - Ictal hemiparesis: differentiation from stroke.
AB  - This is a clinical analysis of four patients who presented with recurrent
      episodes of weakness on one side, feeling of heaviness, numbness, and inability
      to walk. Admission diagnosis was transient ischemic attacks in three patients and
      hemiplegic migraine in one patient. Attacks persisted for few minutes to few
      hours and were stereotyped for each patient and never became generalized during
      the course of the disease. Electroencephalography showed focal slowing and
      epileptiform discharges over parietal region. All patients responded dramatically
      to antiepileptic therapy. This is the first case report of ictal hemiparesis from
      this part of country.

PMID- 11837479
TI  - Disseminated tuberculosis with ocular tuberculoma and disseminated candidiasis in
      acquired immunodeficiency syndrome.
AB  - A 39 years man presented with painless progressive loss of vision and proptosis
      of left eye associated with constitutional symptoms. He was diagnosed to have
      acquired immunodeficiency syndrome (AIDS) with disseminated tuberculosis (TB) and
      invasive candidiasis. The proptosis was due to a retrobulbar mass. The uncommon
      occurrence of retrobulbar tuberculoma and invasive candidiasis is discussed and
      relevant literature is reviewed.

PMID- 11837480
TI  - Calcification of the thoracic ligamentum flavum: a rare cause of myelopathy.
AB  - Compressive myelopathy secondary to ossification or calcification of the
      ligamentum flavum is a rare entity. Clinical features and magnetic resonance
      imaging findings of a patient of dorsal cord compression who improved remarkably
      with surgery are reported.

PMID- 11837481
TI  - Successful pregnancy outcome in advanced chronic renal failure.
AB  - A 24 years female of advanced chronic renal failure due to lupus nephritis
      presented with pregnancy of eight weeks duration she continued the pregnancy
      against medical advice. At 29 weeks gestation further deterioration of renal
      function prompted weekly dialysis and hospitalisation for intensive maternal and
      fetal monitoring. At 35 weeks she was safely delivered by elective caesarian
      section. This is the first case of dialysis during pregnancy to be reported from
      India.

PMID- 11837482
TI  - Abdominal tuberculosis affecting lesser omentum.
AB  - We present a case of a young man who presented with fever and nonspecific
      epigastric symptoms and fluid collection in the lesser omental sac, which was
      proved to be of tubercular etiology.

PMID- 11837483
TI  - Pulmonary nocardial infection and pseudomonas infection of the tongue in a
      patient with dermatomyositis.
AB  - Opportunistic infections in immunocompromised patients are common. We report the
      case of a 63 year old female patient with dermatomyositis who while on oral
      steroids developed nocardial infection of the lung and pseudomonas infection of
      the tongue simultaneously. Nocardial infections are not very commonly seen in
      patients with dermatomyositis. Pseudomonas infection of the tongue is a rarity.
      We report this case for its rarity as regards the type and site of infections and
      review the relevant literature.

PMID- 11837484
TI  - Clubbing and human immunodeficiency virus disease.

PMID- 11837485
TI  - Whipple's disease.
AB  - A 52 year old lady was admitted for progressive pedal oedema over a six year
      period and recent onset of hyperpigmentation. Laboratory investigations revealed
      that she was having a malabsorption syndrome with protein losing enteropathy. In
      view of associated arthralgia and higher mental function disturbances, a clinical
      diagnosis of Whipple's disease was postulated. Duodenal biopsy revealed
      infiltration of the lamina propria with PAS positive macrophages, suggestive of
      Whipple's disease. This case is being reported to highlight that Whipple's
      disease can manifest in the most unsuspecting manner and that early treatment can
      cure the patient.

PMID- 11837486
TI  - Microcystic serous cystadenoma mimicking malignancy in pancreas.

PMID- 11837487
TI  - Serum insulin assay.

PMID- 11837488
TI  - Induced sputum as a diagnostic specimen for Pneumocystis carinii pneumonia in HIV
      positive patients.

PMID- 11837489
TI  - Oral contraceptives and central retinal vein occlusion.

PMID- 11837490
TI  - Drug treatment of mild hypertension in elderly--we should be cautious in some
      patients.

PMID- 11837491
TI  - Relevance of history and clinical examination in medical practice.

PMID- 11837492
TI  - Vitamin D deficiency and DEXA scan.

PMID- 11837493
TI  - The human genome project: implications for the endocrinologist.
AB  - The sequencing of the human genome is a major achievement of our time. This
      article reviews the process and current status of the working draft sequence,
      ways to predict genes and assign function, and conclusions for human biology.
      Gene density is uneven and related to chromosome banding patterns, and the
      estimate of approximately 30,000 genes is lower than expected. Genetic maps for
      men and women differ from each other and from the physical map. Single nucleotide
      polymorphisms occur at an average spacing of 1 kb. Human populations are 99.99%
      identical, and most sequences are shared between people from different
      continents. To illustrate the tools for accessing the human genome sequence,
      searches were performed for genes encoding three categories of growth-related
      proteins, insulin-like growth factor-I (IGF-I) receptor, IGF-binding proteins and
      growth hormone receptor. The results revealed novel details about their genomic
      organization and new predicted transcripts. Impacts on medicine are promised in
      the fields of diagnostics (development of new tests), therapeutics
      (identification of new potential drug targets) and pharmacogenomics (streamlining
      of drug discovery and personalized medicine). Associated ethical, legal and
      social implications and controversies include genetic determinism, informed
      consent, privacy and confidentiality, ownership of genetic information in the
      biotechnology marketplace, and access to genetic healthcare.

PMID- 11837494
TI  - Pro-opiomelanocortin and weight regulation: from mice to men.
AB  - Significant progress in our understanding of the mechanisms of weight homeostasis
      has been made by studying the many genetic mouse models of obesity. Positional
      cloning in the obese mouse led to the discovery of leptin as a feedback messenger
      indicating the adequacy of peripheral energy stores. This was the first in a
      series of important advances in this field. Shortly after this discovery, two
      research laboratories presented evidence for the role of hypothalamic pro
      opiomelanocortinergic (POMC) neurons as important mediators in the regulation of
      feeding behavior, insulin levels and, ultimately, body weight. One of these mouse
      obesity models, the lethal yellow mouse, constitutively overexpresses the agouti
      protein, an endogenous antagonist of both the melanocortin 1 (MC1) and
      melanocortin 4 (MC4) receptors. A second mouse obesity model was created by
      knocking out the MC4 receptor. Investigations using both the autosomal dominant
      lethal yellow mouse and MC4 receptor knockout mouse have provided clear evidence
      for the role of hypothalamic POMC neurons and the MC4 receptor in the regulation
      of weight homeostasis in the rodent. Furthermore, the recent discovery of agouti
      related protein (AGRP), an agouti-like peptide naturally found in the
      hypothalamus, provides further evidence for the importance of POMC neurons in the
      regulation of weight. Although the significance of central POMC and AGRP in the
      rodent is apparent, the role of POMC neurons in the regulation of weight and
      feeding behavior in humans is only now being appreciated.

PMID- 11837495
TI  - How the brain regulates food intake and body weight: the role of leptin.
AB  - The brain plays a key role in the regulation of energy homeostasis, balancing
      food intake and energy expenditure to maintain adipose tissue mass. A widely
      accepted model proposes that energy homeostasis is modulated by hormones that
      circulate in the blood in proportion to adipose tissue mass. A major candidate
      'adiposity signal' to the brain is the adipocyte hormone, leptin; this inhibits
      neuropeptide circuits that promote anabolic metabolism, and stimulates those that
      promote catabolic metabolism. It is hypothesized that leptin-responsive circuits
      in the hypothalamus project to caudal brainstem neuronal groups that integrate
      satiety signals converging on the brain from the stomach and intestine following
      ingestion of food. Leptin signaling to the brainstem via hypothalamic pathways
      potentially increases the brain's motor and autonomic responses to satiety
      signals, leading to smaller individual meals, reduced cumulative food intake, and
      a lower body weight. This mechanism explains how leptin deficiency or defects in
      the brain's processing of leptin signaling can result in a sustained increase in
      food intake and obesity.

PMID- 11837496
TI  - Obesity in childhood and adolescence: clinical diagnosis and management.
AB  - The industrialized countries around the world are experiencing an epidemic of
      childhood obesity. The level of fatness of a child at which morbidity increases
      acutely and/or later in life is determined on an individual basis. Overall,
      however, childhood obesity substantially increases the risk of subsequent
      morbidity whether or not obesity persists into adulthood. The genetic basis of
      childhood obesity has been elucidated to some extent through the discovery of
      leptin, the ob gene product, and the increasing knowledge of the role of
      neuropeptides such as pro-opiomelanocortin, neuropeptide Y and the melanocyte
      concentrating hormone receptors. Environmental and exogenous factors are the main
      contributors to the development of a high degree of body fatness early in life.
      Studies involving twins suggest that approximately 50% of the tendency toward
      obesity is inherited. There are numerous disorders, including a number of
      endocrine disorders, such as Cushing's syndrome and hypothyroidism, and genetic
      syndromes, such as Prader-Labhard-Willi syndrome and Bardet-Biedl syndrome, that
      can present with obesity. A simple diagnostic algorithm allows for
      differentiation between primary and secondary obesity. Among the most common
      sequelae of primary childhood obesity are hypertension, dyslipidemia, back pain
      and psychosocial problems. It is somewhat ironic that the definition of obesity
      in childhood is not an easy one. Direct measurements of body fat content, such as
      hydrodensitometry, bioimpedance, or dual-energy X-ray absorptiometry, are useful
      tools in scientific studies. Body mass index (BMI) is, however, now generally
      accepted to be a good clinical measure for the definition of obesity in children
      and adolescents. In preadolescent boys, BMI also relates to muscle mass and
      should be used for the definition of fat mass with great caution. An increased
      risk of death from cardiovascular disease in adults has been found in patients
      whose BMI had been greater than the 75th percentile as adolescents. Therapeutic
      strategies include psychological and family therapy, modification of lifestyle
      and behavior, and nutritional education. The role of regular exercise and
      exercise programs is emphasized, while surgical procedures and drugs used in
      adult obesity are still not generally recommended for obese children. Obesity is
      the most common chronic disorder in industrialized countries, and its impact on
      individual lives as well as on health economics must be recognized by physicians
      and the public alike. This review aims to increase awareness of the health burden
      and economic dimension of the epidemic of childhood obesity that is occurring
      around the globe.

PMID- 11837497
TI  - Early manifestations of Prader-Willi syndrome: influence of growth hormone.
AB  - Pediatricians and neonatologists now understand the clinical picture of Prader
      Willi syndrome (PWS) in infants as genetic tools are available to confirm this
      diagnosis. Hence, an increasing number of very young, still underweight children
      are being diagnosed with PWS. Some features, such as low prenatal weight and
      below-average height, subsequent poor growth velocity and increased body fat,
      possibly in infancy, may be interpreted as a consequence of early growth hormone
      (GH) deficiency. This raises the question of when is the best time for the
      initiation of GH treatment. This article presents the results of a study in which
      ten very young children with PWS (mean age 1.0 year) were treated with exogenous
      GH. We conclude that GH treatment in young, underweight children, as well as in
      older children with PWS: (1) normalizes growth and body proportions; (2) probably
      reduces fat mass and increases muscle mass; (3) may enhance motor development;
      and (4) is necessary, but obviously not sufficient, to normalize body composition
      and fat distribution. Whether there is a benefit in treating children with PWS
      from such an early age requires longer-term studies.

PMID- 11837498
TI  - Prader-Willi syndrome: how does growth hormone affect body composition and
      physical function?
AB  - Children with Prader-Willi syndrome (PWS) display diminished growth, reduced
      muscle mass (lean body mass), and increased adipose tissue-body composition
      abnormalities resembling those seen in growth hormone (GH) deficiency. Diminished
      GH responses to various provocative agents, low insulin-like growth factor-I
      levels, and the presence of other hypothalamic dysfunction support the presence
      of true GH deficiency (GHD) in many children with PWS. GH treatment in these
      children decreases body fat, and increases linear growth, muscle mass, fat
      utilization and energy expenditure. Strength and agility are also improved. These
      improvements are most dramatic during the first year of GH therapy, and prolonged
      treatment still does not 'normalize' these parameters. The metabolic effects,
      including changes in physical strength and agility, may be the most important
      features for this particular pediatric population. These observations support a
      contribution of GHD to disabilities of children with PWS, and a clinically
      significant benefit of GH treatment.

PMID- 11837499
TI  - The role of thyroid hormone in fetal neurodevelopment.
AB  - Thyroid hormones are necessary for normal brain development during fetal and
      postnatal life. The stage at which the central nervous system becomes thyroid
      hormone sensitive, however, has not been clearly defined. There is increasing
      evidence from epidemiological studies and patient reports that these hormones are
      already needed for orderly development during the first trimester, when the fetus
      is entirely dependent on the maternal transfer of thyroxine, the main substrate
      for intracellular generation of the more active 3,5,3'-triiodothyronine for
      binding to the nuclear hormone receptors. A decrease in maternal circulating
      thyroxine during the first trimester, whether or not accompanied by increased
      circulating thyroid-stimulating hormone, may well result in irreversible mental
      and psychomotor impairments. The very frequent cause of this is an iodine intake
      insufficient to meet the requirements of the pregnant woman. It appears urgent to
      ensure the use of iodine supplements from before or very early in pregnancy, and
      to screen all women for hypothyroxinemia as early as possible. Maternal thyroxine
      continues to be important for the exposure of fetal tissues to adequate amounts
      of this hormone during the second and, possibly, the third trimesters. Premature
      birth, which interrupts this transfer, results in neonatal hypothyroxinemia. This
      is more severe the earlier it occurs during development, and is an important
      cause of the poorer mental and neuromotor development of many preterm infants.
      The possibility of supplying them with thyroxine during the neonatal period is
      being seriously tested.

PMID- 11837500
TI  - Pre- and postnatal brain development in neonates with congenital hypothyroidism.
AB  - Patients with early treated congenital hypothyroidism (CH) often develop
      subnormally and display subtle neurological defects. Can optimal treatment fully
      prevent these abnormalities, especially in patients with severe CH? This question
      was addressed by examining 61 patients (27 severe, 34 mild CH) aged 10-30 months
      using the Bayley Scales of Infant Development, a developmental test appropriate
      for this age. According to age at start of treatment (Early <13 days, Late > or =
      13 days) and levothyroxine dose at the onset of treatment (High > or = 9.5
      microg/kg/day, Low <9.5 microg/kg/day), four treatment groups were formed:
      Early/High, Early/Low, Late/High and Late/Low. Within the severe group, only the
      Early/High-treated patients reached normal developmental scores. Within the mild
      group, the Late/Low-treated infants had lower scores than the other patients with
      mild CH. The results suggest that if patients are treated early with a relatively
      high dosage of levothyroxine, normal psychomotor development can be expected,
      irrespective of the type of CH. When treated later on with a lower dose,
      suboptimal development is likely in infants exhibiting both types of CH. These
      cerebral abnormalities can originate during the pre- or postnatal period. The
      most important argument for a prenatal origin of the abnormalities is the
      relationship between bone age at diagnosis and subsequent developmental scores.
      We found, however, that this relationship can also be the result of late and
      inadequate treatment. In a series of 21 infants with CH (10 severe, 11 mild),
      somatosensory evoked potentials (SEP) were used to assess neurological maturation
      at diagnosis and after 12 months of treatment. At diagnosis, which was late (21
      days after birth), SEP values were significantly less retarded than bone age (3.1
      versus 6.5 weeks of delay, p < 0.001), measured using Senecal's method. At 21
      days, SEP and bone age values did not correlate, but they did correlate at 12
      months (r = 0.47, p = 0.012). Therapy was inadequate in the whole group (mean
      initial dosage of levothyroxine 6.2 microg/kg/day), and in the severe group
      hypothyroidism persisted longer than in the mild group. The results suggest that
      the relationship between bone age and SEP values at 12 months was caused by late
      and inadequate hormone substitution more than intrauterine thyroid hormone
      deficiency.

PMID- 11837501
TI  - Endemic goiter and cretinism: an update on iodine status.
AB  - Iodine deficiency is the most prevalent correctable cause of brain damage in the
      world. Over the past 15 years, great progress has been made towards the
      elimination of iodine deficiency, principally through universal salt iodization.
      Much more needs to be done for countries that are lagging in the effort or that
      have weak systems for sustaining it. The key to maintaining optimal iodine intake
      is regular monitoring, usually by the measurement of urinary iodine
      concentration, linked to a prompt response in the event of abnormal results. If
      the present momentum continues then global iodine sufficiency is possible and, in
      a landmark achievement, iodine deficiency will be the first major non-infectious
      disorder to be eliminated.

PMID- 11837502
TI  - The interaction of glucocorticoids with the growth hormone-insulin-like growth
      factor axis and its effects on growth plate chondrocytes and bone cells.
AB  - Glucocorticosteroids interfere with the growth hormone (GH)-insulin-like growth
      factor-I (IGF-I) axis at different levels, and while low-dose corticosteroids may
      have permissive effects, high-dose, long-term treatment with corticosteroids may
      lead to growth disturbance. The mechanism involved is not clearly understood. The
      Janus kinase (JAK)-2/signal transducers and activators of transcription (STAT)-5
      pathway is the means by which the corticosteroid interacts with the target-cell
      GH receptors. The production of local IGF-I is lowered by the corticosteroid via
      IGF-I transcription inhibition, and the rate of apoptosis is also increased, both
      in growth plate chondrocytes and osteoblast cell lines. GH in vitro and in vivo
      can partly counterbalance the negative effects of glucocorticoids on growth. GH
      has been seen to normalize growth rates in corticosteroid-treated rats as well as
      in children receiving glucocorticoids for immunosuppression following kidney
      transplantation.

PMID- 11837503
TI  - Linear growth in children suffering from juvenile idiopathic arthritis requiring
      steroid therapy: natural history and effects of growth hormone treatment on
      linear growth.
AB  - We assessed linear growth and final height retrospectively in a group of 24
      patients suffering from juvenile idiopathic arthritis (JIA) during childhood who
      had received steroid therapy. In these patients, there was a significant loss of
      height of more than 2 standard deviations during the first years of the disease,
      which correlated positively with the duration of prednisone therapy. After
      remission of the disease and discontinuation of prednisone treatment, 70% of the
      patients achieved catch-up growth, although 30% showed a persistent loss of
      height. Their mean final height was strongly correlated with their mean height at
      the end of steroid therapy and was significantly different between the group of
      patients with catch-up growth and the group without catch-up growth. This pattern
      of growth observed in patients with JIA should help us to define strategies of
      growth hormone (GH) treatment in these patients in order to improve their final
      height. We have previously reported the beneficial effects on growth and body
      composition of 1 year of GH treatment in a group of 14 growth-retarded patients
      suffering from JIA who received glucocorticoid therapy. These patients (n = 13)
      were treated again with GH at the same dosage (0.46 mg/kg/week [0.07 mg/kg/day])
      for another 3-year period. GH treatment markedly increased growth velocity in
      these patients, but had a minor effect on height SDS, suggesting that these
      children will remain short when adults. Starting GH therapy in these patients
      earlier after the onset of the disease may prevent growth deterioration and
      metabolic complications induced by chronic inflammation and long-term steroid
      therapy.

PMID- 11837504
TI  - Inhaled corticosteroids and growth.
AB  - Since inhaled corticosteroids may circulate systemically, a risk of growth
      suppression in asthmatic children treated with these drugs cannot be ruled out.
      When assessing the risk, specific drugs, delivery systems, doses, administration
      regimens, and compliance with treatment regimens must be considered. Although
      reassuring results have been reported, methodological flaws have meant that the
      published follow-up evaluations of final height may not be valid for the sound
      assessment of any growth effects of inhaled corticosteroids. Short-term studies
      suggest that twice-daily administration of budesonide 200-400 microg delivered
      from a metered-dose inhaler with a spacer, dry powder budesonide 200 microg, and
      fluticasone propionate 200 microg per day in children with mild asthma, are not
      associated with growth-rate effects. The risk may become significant with
      budesonide 800 microg administered via a metered-dose inhaler with a spacer, and
      with 400 microg from a dry powder inhaler. The risk of growth suppression can be
      reduced by dosing once daily in the morning. In children with severe asthma, high
      doses of inhaled corticosteroids may be potentially lifesaving and thus outweigh
      the potential risk of mild growth suppression.

PMID- 11837505
TI  - The use of bisphosphonates in children with osteogenesis imperfecta.
AB  - Children with osteogenesis imperfecta (OI) suffer recurrent fractures resulting
      in pain, deformity and disability. There is no accepted medical therapy for the
      condition other than symptomatic pain relief, and surgical correction of the
      deformities. Recent experience with the bisphosphonate group of drugs suggests,
      however, that anti-resorptive therapy may reduce fracture frequency, increase
      bone density, promote remodeling of previously crush-fractured vertebrae, reduce
      chronic pain, and improve mobility in both children and infants. The prospects
      for preventing disability and deformity, and perhaps improving growth in affected
      children are good. Current studies are focusing on the evaluation of the efficacy
      of oral drug therapy, and protocols are under development to evaluate new, more
      efficient molecules. Until gene therapy becomes a reality, the use of
      bisphosphonates appears to be the most efficient way of altering the natural
      course of severe OI, and improving the quality of life of patients.

PMID- 11837506
TI  - The endocrine and metabolic profile of the growth-retarded fetus.
AB  - Intrauterine growth retardation (IUGR) is characterized by the failure of the
      fetus to grow at a normal rate in utero and is associated with a number of
      endocrine and metabolic changes. Our knowledge of the placental nutrient supply
      and the endocrine status of the fetal-placental unit during pregnancies involving
      IUGR has greatly increased over the past decade as a result of the availability
      of fetal blood samples obtained under relatively steady state conditions. These
      studies have provided evidence that the supply of glucose is impaired only under
      severe conditions, whereas placental transfer of amino acids is reduced even in
      fetuses with normal oxygenation and feto-placental blood flow. Moreover,
      significant in utero relationships have been reported between fetal weight and
      circulating levels of growth factors such as insulin-like growth factor-I and
      leptin. When measured per kg fetal weight, however, levels of leptin are
      significantly higher in growth-retarded fetuses, with abnormal feto-placental
      blood flow and reduced oxygen content. The metabolic and endocrine changes
      observed should be interpreted in relation to the severity of the disease.

PMID- 11837507
TI  - The 'gold standard' for optimal fetal growth and development.
AB  - It is now becoming accepted that birth size per se is too crude an outcome
      measure to be used for the assessment of optimal intrauterine growth and
      development, and that a new vision of optimal fetal development is required for
      the 21st century. This will need to take account of both short- and long-term
      outcomes, to recognize that maternal body composition and diet can have long-term
      effects without necessarily affecting size at birth, and to take account of
      important interactions between the pre- and postnatal environments. At present,
      our understanding is limited and new definitions should only be considered as
      working hypotheses. Nonetheless, it is possible to begin to set out a framework
      for defining optimal fetal growth and development. This acknowledges the
      importance of developmental adaptations to alterations in the nutrient and
      hormonal milieu in utero and could have a major impact on human health in the
      century to come.

PMID- 11837508
TI  - New insights into the postnatal growth of infants born 'idiopathic' small for
      gestational age.
AB  - Infants born small for gestational age (SGA) are defined as those with a birth
      weight and/or birth length below two standard deviations for gestational age.
      Postnatal catch-up growth is absent in 8-12% of children born SGA and these
      children achieve adult heights far below their target height. The objectives of
      our retrospective study were to confirm the prevalence of catch-up growth and to
      refine the kinetics of the catch-up process. The 'Lyon series' of patients
      consisted of 179 children with 'idiopathic' SGA, of whom 8% did not achieve catch
      up growth (i.e. their height remained below -2 SD throughout the study). The
      number of days that the mother was hospitalized before delivery was found to be
      significantly correlated with lack of catch-up growth. Maternal hypertension,
      term delivery and postnatal parenteral nutrition were also associated with lack
      of catch-up growth, but the relationship was not significant. In addition, an
      oscillatory growth velocity pattern was observed in boys and girls born SGA, with
      alternating periods of growth acceleration and deceleration. This suggests that
      catch-up growth is regulated in a sophisticated way by the hypothetical
      'Somatostat', although further confirmation of this process is needed.

PMID- 11837509
TI  - Hormonal determinants of pubertal growth.
AB  - Pubertal growth results from increased sex steroid and growth hormone (GH)
      secretion. Estrogens appear to play an important role in the regulation of
      pubertal growth in both girls and boys. In girls, however, estrogens cannot be
      the only sex steroids responsible for pubertal growth, as exogenous estrogens do
      not initiate a complete growth spurt. We therefore investigated the levels of the
      different sex steroids and GH, and related them to pubertal growth. In addition,
      we studied the process of bone maturation and mineralization during this period.
      Levels of both estrogens and androgens were found to increase at the start of the
      female pubertal growth spurt, and it was demonstrated that height velocity is
      related to levels of GH, estradiol and androstenedione, but not
      dehydroepiandrosterone sulfate. In boys, GH, testosterone and estradiol increased
      at the time of peak height velocity. Bone mineralization increased as puberty
      began, and was associated with the increase in height velocity. Osteocalcin, a
      marker of bone formation, declined when height velocity decreased, although bone
      maturation progressed at a steady rate. We conclude, therefore, that in girls,
      the concerted actions of estradiol, GH and androstenedione play a role in the
      pubertal growth spurt, whereas in boys this role is fulfilled by testosterone, GH
      and estradiol. During puberty, an advanced rate of bone maturation with respect
      to cross-sectional standards is a physiological phenomenon.

PMID- 11837510
TI  - The estrogen receptor in the growth plate: implications for pubertal growth.
AB  - It is well established that estrogen is essential for statural growth during
      puberty, but until recently it was generally accepted that the role of estrogen
      was negligible during puberty in boys. Clinical findings in three male patients,
      one with an inactivating mutation in the estrogen receptor and two with P-450
      aromatase deficiency, have, however, advanced our knowledge of the role of
      estrogen in the male. It has become apparent that estrogen (1) initiates the
      pubertal growth spurt, (2) causes growth plate fusion at the end of puberty, and
      (3) augments accrual of bone during puberty. Two estrogen receptors (alpha and
      beta) mediate the actions of estrogen, and the presence of both has been
      demonstrated in the growth plate. The mechanism by which estrogen acts locally on
      the growth plate, however, remains largely unknown. With the recent development
      of knockout models for both estrogen receptors, attempts are being made to
      unravel the local actions of estrogen in order to characterize further their
      roles in the regulation of longitudinal growth.

PMID- 11837511
TI  - Final height prediction in constitutional growth delay.
AB  - Methods to predict the final stature of children are commonly used in pediatric
      endocrinology since one of the questions that parents have about their short
      children is how tall he or she will be as an adult. There is a disparity between
      what the family wants and what the physician expects from a height prediction,
      and what is available. The family wants an accurate prediction of final height
      for their child. What the physician expects is a well-validated and accurate
      technique applicable to individual children and that can be trusted for use, not
      just with normally growing children, but also with children exhibiting abnormal
      growth. Unfortunately, what is available from the generally used height
      prediction methods are estimates, with fairly broad error limits, based on groups
      of normal children followed to adult height. The underlying problem in predicting
      final height is that there is considerable individual variation in the timing and
      tempo of puberty and the pubertal growth spurt in individual children which
      significantly impacts the validity of the techniques when applied to individual
      children. This article reviews the methods of height prediction that are
      available, and their limitations.

PMID- 11837512
TI  - Treatment of delayed male puberty: efficacy of aromatase inhibition.
AB  - We hypothesized that inhibition of estrogen synthesis would delay maturation of
      the growth plates and ultimately result in increased adult height in boys with
      delayed puberty. We conducted a randomized, double-blind, placebo-controlled
      study in which we treated boys with constitutional delay of puberty with
      testosterone plus placebo (testosterone-placebo) or with testosterone plus
      letrozole (testosterone-letrozole). Letrozole effectively inhibited estrogen
      synthesis: 17beta-estradiol concentrations increased in the testosterone-placebo
      group, but in the testosterone-letrozole group, no such increase was observed
      until letrozole treatment was discontinued. After 1.5 years, bone age had
      advanced by 1.7 +/- 0.3 years in the testosterone-placebo group, but by only 0.9
      +/- 0.2 years in the testosterone-letrozole group (p = 0.02). Predicted adult
      height did not change significantly in the testosterone-placebo group, whereas in
      the testosterone-letrozole group the increase was 5.1 +/- 1.2 cm (p = 0.004). Our
      findings suggest that, if estrogen action is inhibited in growing adolescents,
      adult height will increase. This observation provides a rationale for studies
      aimed at delaying bone maturation in several growth disorders.

PMID- 11837513
TI  - Multifactorial regulation of plasma natriuretic peptides calls for supplementary
      measurements.

PMID- 11837514
TI  - Clinical relevance of ischemic preconditioning.
AB  - The mechanisms of ischemic cell death and reperfusion injury in the myocardium
      and the ways to limit these have been under extensive research for decades. The
      discovery of the phenomenon of ischemic preconditioning, i.e. endogenous
      protection against ischemia-reperfusion injury obtained by one or more brief
      preceding episodes of ischemia, really boosted this research 15 years ago. Even
      though extensive research in experimental animals has provided data on the
      cellular mechanisms of ischemic preconditioning, such as adenosine receptor
      activation, opening of mitochondrial adenosine triphosphate (ATP)-sensitive
      potassium channels and production of endogenous protective stress proteins,
      direct clinical applications are still missing. The purpose of this study is to
      summarize the latest progress in solving the cellular and molecular mechanisms of
      the phenomenon, as well as the evidence for the existence of this phenomenon in
      humans and its clinical relevance.

PMID- 11837515
TI  - Plasma N-terminal proatrial natriuretic factor can predict normal pulmonary
      capillary wedge pressure in cardiac transplant recipients.
AB  - BACKGROUND: Plasma N-terminal proatrial natriuretic factor (proANP) is closely
      related to atrial filling pressure, but this may be distorted in heart transplant
      recipients. OBJECTIVE: The aim of this study was to examine the usefulness of
      proANP as a non-invasive marker of cardiac filling pressure in transplanted
      patients with normal to moderately elevated serum creatinine (s-creatinine).
      METHODS: Blood was sampled at rest for analysis of proANP from 220 patients 1-13
      (median 4) years after orthotopic heart transplantation undergoing routine
      diagnostic catheterization. RESULTS: In multivariate analysis proANP was
      significantly positively related to s-creatinine, mean pulmonary capillary wedge
      pressure (PCWP) and time after transplantation and negatively related to
      haemoglobin and cardiac index. All the patients with proANP below 1140 pmol/l had
      normal PCWP (<13 mmHg). The area under the receiver-operating characteristic
      curve for proANP for the detection of PCWP > 13 mmHg was 0.81. The positive
      predictive value of proANP for detection of increased PCWP was very low.
      CONCLUSION: A low proANP had a 100% negative predictive value for increased
      atrial pressure but the low positive predictive value makes proANP unsuitable as
      an indicator of increased atrial pressures in heart transplanted patients.

PMID- 11837516
TI  - Plasma N-terminal pro-atrial natriuretic peptide predicts death after premature
      myocardial infarction, but not as well as radionuclide ejection fraction. A ten
      year follow-up study.
AB  - OBJECTIVE: To assess N-terminal pro-atrial peptide (N-ANP) as a predictor of
      total and cardiac death in patients with previous premature myocardial infarction
      (MI). DESIGN: In this prospective cohort study, we measured plasma N-ANP by ELIZA
      assays and ejection fraction (EF) by radionuclide ventriculography in a cohort of
      247 patients (193 men and 54 women) who had had MI at a relatively young age
      (males: first MI at age < or =55; females <60). RESULTS: After 10 years 44
      patients had died, 36 from cardiac causes. After using a stepwise procedure to
      adjust for other prognostic factors (i.e. plasma total homocysteine (tHcy), C
      reactive protein and age), the relative risk (RR) was 2.00 (95% confidence
      interval (CI) 1.05-3.80) (p = 0.03) for death of all causes and 2.32 (95% CI 1.19
      4.55) (p=0.01) for cardiac death when the top quartile was compared to the three
      lower quartiles of N-ANP. When radionuclide EF entered the Cox model, N-ANP
      became insignificant as a predictor of mortality. CONCLUSION: N-ANP was a
      significant predictor of total death and cardiac death in young survivors of MI,
      but radionuclide EF was a more independent prognostic variable.

PMID- 11837517
TI  - Left ventricular function and infarct size 20 months after primary angioplasty
      for acute myocardial infarction.
AB  - OBJECTIVE: To study changes in left ventricular function and infarct size during
      long-term follow-up after acute myocardial infarction treated with primary
      angioplasty. DESIGN: From 1996 to 1998, 100 consecutive patients were treated
      with primary angioplasty for acute ST-elevation myocardial infarction.
      Angioplasty was successful in 95% of the patients. Global left ventricular
      ejection fraction (LVEF) was determined by radionuclide ventriculography before
      discharge, after 6 weeks and after a mean follow-up time of 20 months. Infarct
      size was assessed by technetium 99m-tetrofosmin myocardial perfusion tomography
      (SPECT) at rest, performed at the same time intervals. RESULTS: Mean LVEF was 56%
      at discharge, 55% after 6 weeks and 57% after 20 months of follow-up. No
      significant improvement in LVEF was observed. Only 8% of the patients at follow
      up had LVEF lower than 40%. After 1 week, a mean perfusion defect of 19% was
      measured by SPECT. After 6 weeks and 20 months of follow-up, the mean perfusion
      defects were reduced to 14% (p < 0.001) and 15%, respectively. CONCLUSION: Left
      ventricular function was well preserved with a mean LVEF of 57% 20 months after
      primary angioplasty for acute myocardial infarction. No significant change in
      LVEF was observed from 1 week after angioplasty to follow-up. Infarct sizes as
      assessed by SPECT imaging with tetrofosmin were reduced from 1 to 6 weeks, but
      did not change further during long-term follow-up. The reduction in the perfusion
      defects over time was probably due to gradual relief of stunning.

PMID- 11837518
TI  - Biplane long-axis magnetic resonance imaging. Survey projections for rapid
      estimation of left ventricular mass and global function.
AB  - OBJECTIVE: To evaluate the accuracy and precision of biplane long-axis magnetic
      resonance imaging (MRI) and two-dimensional (2D)-echocardiography, for the
      assessment of left ventricular (LV) mass and volumes, with multislice short-axis
      MRI as reference standard. DESIGN: Forty-five cardiac patients and four
      volunteers with varying LV dilatation and hypertrophy were examined by biplane
      long-axis gradient-echo MRI, 2D-echocardiography, and multiple short-axis
      gradient-echo MRI. RESULTS: Compared with multislice MRI, the accuracy, i.e. the
      coefficient of variation (c.v.) of inter-method differences of measured
      variables, was median 15.7% for biplane MRI and 18.5% for 2D-echocardiography.
      The precision, expressed as the c.v. of repeated measurements, was median 8.5%
      for multislice MRI, 9.5% for biplane MRI and 12.4% for 2D-echocardiography. For
      the determination of LV mass index, MRI was significantly more precise (c.v.: 6.0
      8.4%) than 2D-echocardiography (c.v.: 13.7-14.3%, p < 0.05). CONCLUSION: Biplane
      long-axis MRI is a fast and simplified method, offering the advantage of
      displaying anatomy and function in recognizable projections. For the estimation
      of LV mass and volumes, biplane MRI had an acceptable accuracy, and a precision
      that did not differ significantly from that of multislice MRI.

PMID- 11837519
TI  - The role of cerebral microdialysis in predicting the outcome after experimental
      hypothermic circulatory arrest.
AB  - OBJECTIVE: To evaluate whether and which of the cerebral microdialysis parameters
      are predictive of postoperative outcome after an experimental 75-min period of
      hypothermic circulatory arrest (HCA) in a chronic porcine model. DESIGN: Seventy
      four juvenile female pigs underwent a 75-min period of HCA at 20 degrees C. A
      microdialysis catheter was placed into the cortex gray matter and brain
      extracellular concentrations of glucose, lactate, glycerol and glutamate were
      measured throughout the experiment by enzymatic methods using a microdialysis
      analyzer. Surviving animals were sacrificed on the 7th postoperative day and
      histopathological examination of the brain was performed. RESULTS: Brain glucose
      concentrations were higher in animals that survived (p = 0.017), especially from
      the 90-min until the 7-h interval after the start of rewarming. The blood venous
      concentrations of glucose were also higher among survivors, and correlated
      significantly with the brain glucose levels at 2-h and 4-h intervals after the
      start of rewarming. Higher concentrations of brain lactate, glycerol and
      glutamate were observed throughout the study among animals that died
      postoperatively. Brain glutamate and glycerol concentrations were significantly,
      negatively correlated with brain glucose concentrations. The lactate/glucose
      ratio was significantly lower among survivors during the postoperative period
      (p=0.014). Furthermore, brain glucose concentrations were higher and brain
      glycerol concentrations lower among the animals that did not develop brain
      infarction, but such differences did not reach statistical significance.
      CONCLUSION: Cerebral microdialysis is a useful tool for cerebral monitoring
      during experimental HCA. Low brain glucose concentrations and high brain
      lactate/glucose ratios after HCA are strong predictors of postoperative death.
      Brain glucose concentrations are negatively correlated with brain glycerol and
      glutamate concentrations.

PMID- 11837520
TI  - Impaired contractility of left-over vein grafts used for CABG and the possible
      trauma caused by air exposure.
AB  - OBJECTIVE: The patency of vein grafts limits the long-term results after bypass
      surgery. Vein graft trauma may contribute to the clinical results. DESIGN: Left
      over pieces of vein after routine coronary bypass surgery were compared with
      references of the same vein that were stored with maximum care. Blood perfusion
      (20 h, 37 degrees C) was also tested to evaluate possible recovery. Vessel rings
      were measured by isometric tone recordings. RESULTS: Left-over veins showed a
      contractile dysfunction compared to reference (p < 0.01-0.001, n = 13), and that
      did not recover after blood perfusion. Four trauma models were tested, using
      saphenous vein graft (SVG)-references (n = 5). Chemical exposures (0-90 min) to
      NaCl-papaverin or cardioplegic medium affected the baseline (p < 0.05-0.01). With
      mechanical distension, up to 450 mmHg leak testing, an increased norepinephrine
      (NE) reactivity appeared. Air contact, 20 min, reduced the NE reactivity to half
      maximum (p < 0.05). Longer exposures (40-60 min) completely abolished the
      contractility. CONCLUSIONS: The saphenous vein smooth muscle function appeared
      permanently traumatized following routine harvesting and handling. Air exposure
      gave dramatic deterioration and could in theory contribute to hamper the long
      term results after bypass surgery.

PMID- 11837521
TI  - Adenosine in myocardial protection given through three windows of opportunity. An
      experimental study with pigs.
AB  - OBJECTIVE: Adenosine (ADO) has been shown to have beneficial effects against
      tissue injury after myocardial ischemia. However, the timing and dose of ADO
      administration have not been defined. This study was designed to determine the
      cardioprotective effect of exogenous ADO in an experimental open heart surgery
      model in pigs. DESIGN: The animals were openly divided into two groups both
      undergoing 30 min of total cardiac arrest. In the control group animals received
      cold crystalloid cardioplegic solution. In the ADO group ADO was added to
      cardioplegic solution and in addition ADO was infused to the superior vena cava
      for 2 h starting 30 min before cardiac arrest. The pumping function of the heart
      was measured with echocardiography and myocardial blood flow was measured with
      microspheres and positron emission tomography (PET). Cardiomyocyte apoptosis was
      detected and tumor necrosis factor (TNF) levels were measured. RESULTS: Better
      post-ischemic pumping function was found in the ADO group (relative decrease
      43.7% vs 55.4%, p = 0.20 between the groups). The cardiac output decreased
      significantly from the baseline values (p < 0.05 in both groups). There was a
      temporary decrease in myocardial blood flow post-ischemically, followed by a
      compensatory increase during the later reperfusion period. The cardiomyocyte
      apoptosis was induced significantly in both groups. CONCLUSIONS: In this
      experiment two important details were noticed. Firstly, cardiomyocyte apoptosis
      is involved in ischemia-reperfusion injury associated with open heart surgery.
      Secondly, PET is a comparable method with the microsphere technique when coronary
      flow is studied. No significant effects of ADO against ischemia-reperfusion
      injury could be shown. However, there were some signsof positive outcome, even
      though statistical significance could not be reached.

PMID- 11837522
TI  - Early intervention for acute back injury: can we finally develop an evidence
      based approach?
AB  - OBJECTIVE: Several reviews of the treatment of acute low back pain have been
      published in the past and have formed the basis of clinical guidelines. However,
      these lack consistency in some areas and valid data in others. As the literature
      in this field has continued to expand, the present review was undertaken to
      establish whether the guidelines in current use are supported by more recently
      published, scientifically rigorous research, and whether additional consensus
      regarding treatment of acute low back injury has been forthcoming in recent
      years. DESIGN: A review, and critical analysis, of literature relating to the
      treatment of acute low back pain that has been published since the production of
      the currently used clinical guidelines. The guidelines have been reviewed to
      assess whether their recommendations remain supportable. CONCLUSIONS: Recent
      research appears to support current clinical guidelines, i.e. exercise may have a
      positive effect while bed rest is ineffective and may be harmful, simple
      analgesics and nonsteroidal anti-inflammatory drugs (NSAIDs) have short-term
      benefits, and spinal manipulation may be effective in the first four weeks; no
      evidence was found for traction or back schools. However, we need more randomized
      controlled trials of treatments shown to be successful with the chronic
      population, e.g. focused on understanding psychological determinants, and using a
      multidisciplinary biopsychosocial approach. In the future this may help us to
      prevent acute low back progressing to the chronic state.

PMID- 11837523
TI  - Association between hypermobility and congenital limb deficiencies.
AB  - OBJECTIVE: To determine the prevalence of hypermobility in individuals with
      congenital limb deficiencies and whether congenital limb loss is associated with
      increased laxity in the remaining joints. STUDY DESIGN: All data were collected
      during the individuals' visits to the prosthetic clinic. SETTING: The subjects
      were evaluated at the Subregional Disablement Services Centre at University
      Hospital of South Manchester, UK. SUBJECTS: Forty-five individuals with
      congenital limb deficiencies were studied (male/female 27 :18; ages 6-31 years).
      OUTCOME MEASURE: A modified version of the nine-point Beighton Score for
      hypermobility was used, using the presently accepted criteria for diagnosing
      hypermobility. Any individual who scored 3 or more points was considered to have
      joint hypermobility. RESULT: Of the 45 individuals with congenital limb
      deficiencies, 71% had at least one hypermobile joint, whereas 38% had three or
      more features of hypermobility, with female/male ratio of 2.75:1. CONCLUSION: Our
      results show an increase in joint hypermobility (laxity) in individuals born with
      congenital limb deficiencies compared with the prevalence of this condition in
      the general population. As joint hypermobility may predispose individuals to low
      back pain, joint effusion, recurrent joint dislocation and ligament rupture, it
      is useful to identify those individuals with hypermobility.

PMID- 11837524
TI  - Correspondence of the functional independence measure (FIM) self-care subscale
      with real-time observations of dementia patients' ADL performance in the home.
AB  - OBJECTIVE: To determine if caregivers of dementia patients can validly report (a)
      the level of patient activities of daily living (ADL) dependence and (b) the
      amount of time they spend providing ADL assistance. DESIGN: Seven ADLs were
      assessed through caregiver report using the Functional Independence Measure (FIM)
      and then videotaped. Videotapes were coded using a computer-assisted data
      collection system that documented the nature and duration of caregiver assistance
      provided during ADLs. SETTING: The study took place in the homes of the caregiver
      patient dyads. SUBJECTS: Twenty-one people with dementia and their primary
      caregivers participated in the study. MAIN OUTCOME MEASURES: Data analysis
      examined (a) the degree to which caregiver-reported FIM scores corresponded to
      FIM scores derived from the observational data and (b) the extent to which
      caregivers' estimates of ADL assistance time corresponded to the assistance time
      observed during ADL interactions. RESULTS: For all ADLs, caregiver-reported FIM
      scores were correlated significantly with observation-derived FIM scores (r(s)
      values ranged from 0.620 to 0.909), and means were similar. Assistance durations
      were also significantly correlated for some ADLs, but means were significantly
      different, indicating poor correspondence. CONCLUSIONS: Although caregivers of
      dementia patients can describe the nature of their ADL assistance with reasonable
      accuracy, they consistently overestimate their ADL assistance time, suggesting
      that caregiver reports of ADL assistance duration be used with caution.
      Additionally, the degree to which the assistance provided corresponds to the
      assistance actually needed needs to be addressed in future studies.

PMID- 11837525
TI  - Characteristics of injured children attending the emergency department: patients
      potentially in need of rehabilitation.
AB  - OBJECTIVE: To provide an epidemiological overview of the characteristics of
      injured children and to compare hospitalized and nonhospitalized injured children
      to identify predictors of hospitalization and, with that, possible predictors of
      disablement. DESIGN: Retrospective analysis of data obtained from a computerized
      trauma registration system and medical records. SETTING: Department of
      Traumatology, University Hospital Groningen, the Netherlands. SUBJECTS: Children
      (0-19 years) injured in 1996 and 1997 (n = 5,057). RESULTS: The majority of
      children were injured in home and leisure accidents (53%) and sustained minor
      injuries. Only 55 (1%) children were severely injured (Injury Severity Score
      (ISS) > or = 16). Overall, 512 (10%) patients required hospitalization, 19
      children were referred to a rehabilitation centre, and 24 children died due to
      their injuries. The majority of these patients were injured in traffic. Compared
      with the group of nonhospitalized patients, the group of hospitalized patients
      consisted of more males and traffic victims, were more severely injured and
      sustained more head/neck, spine, and thorax and abdomen injuries. Nonhospitalized
      patients incurred proportionally more upper and lower extremity injuries. The
      ISS, the body region of most severe injury, and injury cause (traffic accidents)
      were significant predictors of hospitalization. CONCLUSIONS: Young traffic
      victims, severely injured children in terms of high ISS scores, and children with
      injuries affecting the head/neck/face or thorax/abdomen carry the highest risk of
      hospitalization.

PMID- 11837526
TI  - Stroke patients' and therapists' opinions of constraint-induced movement therapy.
AB  - OBJECTIVE: To determine the opinions of patients with stroke and therapists about
      constraint-induced movement therapy (CIT). SUBJECTS AND INTERVENTION: Two hundred
      and eight patients with stroke in the northeastern USA responded to a self-report
      questionnaire administered through the mail and via telephone interviews. A
      similar questionnaire was administered to 85 physical and occupational therapists
      in the northeastern USA during their clinical staff meetings. The questionnaire
      described CIT to participants using excerpts from a recently published CIT study.
      Subjects then responded to various statements concerning their opinions of the
      protocol and supplied rationale for their opinions. RESULTS: Sixty-eight per cent
      of patients said they were not interested in participating in CIT, citing
      concerns with the practice schedule and the restrictive device schedule.
      Therapists cited concerns about patient adherence and safety, and speculated that
      facilities may not have the clinical resources to provide CIT. CONCLUSIONS:
      Patients with stroke and therapists in some environments may hold sceptical views
      about the utility of CIT. Although it has been shown to be effective in
      laboratory research, CIT may have low clinical practicality in some environments.

PMID- 11837527
TI  - Speech and language therapy for dysarthria due to nonprogressive brain damage: a
      systematic Cochrane review.
AB  - BACKGROUND: Dysarthria is a common sequel of nonprogressive brain damage
      (typically stroke and traumatic brain damage). Impairment-based therapy and a
      wide variety of compensatory management strategies are undertaken by speech and
      language therapists with this patient population. OBJECTIVE: To determine the
      efficacy of speech and language therapy interventions for adults with dysarthria
      following nonprogressive brain damage. DESIGN: Systematic review. SEARCH
      STRATEGY: This review has drawn on the search strategies developed for the
      following Cochrane Groups as a whole: Stroke, Injuries, and Infectious Diseases.
      Relevant trials were identified in the Specialised Registers of Controlled
      Trials. We also searched the trials register of the Cochrane Rehabilitation and
      Related Therapies Field. The Cochrane Controlled Trials Register, MEDLINE,
      EMBASE, CINAHL, PsycLIT, and Linguistics and Language Behavior Abstracts were
      electronically searched. Hand-searching of the International Journal of Language
      and Communication Disorders and of reference lists from relevant articles and
      conference proceedings was also undertaken. Colleagues were approached to
      identify other possible published and unpublished studies. SELECTION CRITERIA:
      Unconfounded randomized controlled trials. DATA COLLECTION AND ANALYSIS: One
      reviewer assessed trial quality. Two co-reviewers were available to examine any
      potential trials for possible inclusion in the review. MAIN RESULTS: No trials of
      the required standard were identified. REVIEWERS' CONCLUSIONS: There is no
      evidence of the quality required by this review to support or refute the
      effectiveness of speech and language therapy interventions for dysarthria
      following nonprogressive brain damage. There is an urgent need for good quality
      research in this area.

PMID- 11837528
TI  - Systematic reviews in rehabilitation for stroke: issues and approaches to
      addressing them.
AB  - OBJECTIVES: To describe the problems encountered when undertaking systematic
      reviews of rehabilitation and to give advice to reviewers about ways of
      addressing these issues. BACKGROUND: Evidence-based practice has become
      established as a way of linking clinical practice with research evidence. The
      most robust evidence is usually considered to be that from randomized controlled
      trials, and from systematic reviews of these trials. However, most reviews have
      focused on drug and surgical interventions, and few reviews have been produced in
      the field of rehabilitation. This may be due to the unique difficulties that are
      posed by reviews in this area. EXPERIENCE OF SYSTEMATIC REVIEWS IN APHASIA: We
      describe the challenges that occurred when carrying out systematic reviews of
      speech and language therapy for aphasia following stroke, and of ways to deliver
      rehabilitation services to people who have suffered a stroke. Issues arose at all
      stages of the reviews and included: using expertise; planning the review;
      defining the health care problem, patients, outcomes and interventions of
      interest; searching for, interpreting and synthesizing the results of the studies
      identified; and deriving implications from the review. Suggestions made to
      address these challenges include: developing a suitable team of reviewers; using
      inclusive and broad criteria for inclusion of trials to a review; developing
      appropriate search strategies; and using caution in arriving at conclusions. It
      is important to be explicit about decisions made during the review process
      concerning how to handle the challenges. Practical advice about carrying out
      reviews in the field of stroke rehabilitation is likely to be helpful to
      reviewers of other rehabilitative interventions. There are likely to be
      relatively few studies available for such reviews, and limitations in drawing
      specific practical conclusions. Such undertakings are, however, useful in setting
      the agenda for further research.

PMID- 11837529
TI  - The Guy's Neurological Disability Scale in patients with multiple sclerosis: a
      clinical evaluation of its reliability and validity.
AB  - OBJECTIVE: To establish reliability and validity of the Guy's Neurological
      Disability Scale (GNDS) for the assessment of patients with multiple sclerosis
      (MS) and to investigate whether it can be used by postal questionnaire. DESIGN:
      An observational study assessing one group of 22 patients using the GNDS face-to
      face, repeating the assessment two or three weeks later with other tests; and
      assessing a second group of 21 patients first using a postal version of the GNDS
      and then seeing them face-to-face. SETTING: Patients in the community attending a
      day centre or a voluntary support group. SUBJECTS: Patients with multiple
      sclerosis. MEASURES: The GNDS was the primary measure, and was compared with the
      Barthel Index, the Expanded Disability Status Scale (EDSS), the Short Orientation
      Concentration and Memory Test, the Nine-hole Peg Test, the Rivermead Mobility
      Index, the Hospital Anxiety and Depression Scale, the Fatigue Severity Scale,
      visual acuity assessment, swallowing 50 ml of water, and a clinical assessment of
      dysarthria. RESULTS: The test-retest reliability of the GNDS total score (r=
      0.972) and each of its components (r varied from 0.685 to 0.987) was good. When
      compared with the EDSS or the Barthel, the GNDS had good validity (respectively r
      = 0.636 and r = -0.757). The validity was also measured for the different areas
      of the GNDS by comparison with corresponding indices or test. The results varied
      from good to excellent (r from -0.557 to 0.910). The results were only a little
      less reliable when a postal questionnaire was used. CONCLUSION: The GNDS is a
      valid and reliable tool for the assessment of MS patients. The test-retest
      correlation varies from good to excellent. It can be used as postal questionnaire
      even if, as expected, the interviewer-administered method shows slightly better
      results.

PMID- 11837530
TI  - Lifestyle risks for three disease outcomes in spinal cord injury.
AB  - OBJECT: The majority of research focusing on lifestyle risks in the spinal cord
      injured population to date has mainly been descriptive in nature. Limited
      research has examined the relationships between lifestyle risks and morbidity.
      This study was undertaken to quantify the associations between selected lifestyle
      risks and morbidity associated with three top causes of mortality in adults with
      spinal cord injury (SCI). METHOD: Ninety-seven adults who had incurred a spinal
      cord injury between 1972 and 1992 were interviewed over the telephone to assess
      morbidity and lifestyle exposure history. Logistic regression modelling was used
      to assess the association between lifestyle risks and cardiovascular, respiratory
      and urinary tract disorders. RESULTS: Risk of cardiovascular morbidity was found
      to be positively associated with age and duration of cigarette use. Risk of
      respiratory morbidity was found to be positively associated with quadriplegia,
      number of cigarettes smoked per day, and the interaction between cigarettes
      smoked per day and excessive alcohol consumption. Risk of urinary tract morbidity
      was found to be positively associated with a complete lesion, number of
      cigarettes smoked per day and, surprisingly, physical activity. Risk of urinary
      tract morbidity was negatively associated with monthly alcohol consumption, a
      traumatic injury and the interaction between monthly alcohol consumption and a
      complete lesion. CONCLUSION: With respect to the three morbidity outcomes in this
      study, cigarette smoking is the most damaging lifestyle behaviour in the spinal
      cord-injured population. Attention and resources should be directed towards SCI
      specific smoking prevention and cessation programmes to prevent the development
      and exacerbation of chronic diseases in this unique population. Further research
      is needed to fully understand the associations between lifestyle and chronic
      diseases in the SCI population.

PMID- 11837531
TI  - Pathology of radiation myelopathy.
AB  - Radiation myelopathy is principally a white matter injury of the spinal cord
      induced by ionizing radiation after a certain latent period. It involves
      myelinated fibers and blood vessels, and the lateral funiculi is most
      preferentially affected. Several factors, such as radiation dose, fractionation
      or linear energy transfer, modify its occurrence and severity. Although glial
      cells and vascular endothelium are proposed to be the main targets, and to play a
      role in the pathogenesis of radiation myelopathy, experimental researches support
      that radiation-induced vascular damage resulting in vascular hyperpermeability
      and venous exudation is a basic process. Effect of ionizing radiation on each
      cellular component of the central nervous system, their contribution to radiation
      myelopathy, mechanisms of selective permeability and remaining problems are
      discussed.

PMID- 11837532
TI  - Spatial correlations between the vacuolation, prion protein deposits, and
      surviving neurons in the cerebral cortex in sporadic Creutzfeldt-Jakob disease.
AB  - In the cerebral cortex of cases of sporadic Creutzfeldt-Jakob disease (sCJD), the
      vacuolation (spongiform change) and PrP deposits are aggregated into clusters
      which are regularly distributed parallel to the pia mater. The objective of the
      present study was to determine the spatial relationships between the clusters of
      the vacuoles and PrP deposits and between the pathological changes and variations
      in the density of surviving neurons. In areas with low densities of pathological
      change, clusters of vacuoles were spatially correlated with the surviving neurons
      and not with the PrP deposits. By contrast, in more significantly affected areas,
      clusters of vacuoles were spatially correlated with those of the PrP deposits and
      not with the surviving neurons. In addition, areas with a high density of
      vacuoles and a low density of PrP deposits exhibited no spatial correlations
      between the variables. These data suggest that the spatial relationships between
      the vacuolation, PrP deposits and surviving neurons in sCJD depend on the density
      of lesions present. Differences in the pattern of correlation may reflect the
      developmental stage of the pathology in particular cortical areas.

PMID- 11837533
TI  - Frequency and distribution of TUNEL-positive neurons in brains of dementia with
      Lewy bodies: comparison with those in brains of Alzheimer's disease.
AB  - The present study investigated the frequency and distribution of TUNEL-positive
      neurons in brains of dementia with Lewy bodies (DLB) in comparison with those in
      brains of Alzheimer's disease (AD), Down syndrome (DS) and non-demented elderly
      persons. In DLB brains, TUNEL-positive neurons were increased in frequency
      compared with those in non-demented elderly brains, and showed a distribution
      similar to those in AD and DS brains. DLB cases with TUNEL-positive neurons
      showing severe Lewy pathology were all neocortical type, while DLB cases of the
      limbic type showing mild Lewy pathology did not demonstrate TUNEL-positive
      neurons. In addition, we investigated the relationships between TUNEL-positive
      neurons and pathological hallmarks of DLB or AD brains. TUNEL-positive neurons
      had no Lewy bodies or neurofibrillary tangles, and were not located within
      amyloid deposits. These findings suggest that neuronal damage showing DNA
      fragmentations occurs in DLB brains as well as in AD and DS brains, and that it
      is accelerated by progression of Lewy pathology as well as Alzheimer pathology,
      although it is not directly related to their pathological hallmarks.

PMID- 11837534
TI  - An autopsy case of hemilaterally dominant and systematic/extensive border zone
      infarction: sequela of preceding atherosclerotic obstruction of one common
      carotid artery followed by repeated episodes of systemic hypotension.
AB  - A 68-year-old man was admitted to St Marianna University Hospital on account of
      loss of consciousness with left hemiplegia. During the hospital recovery course
      with a rehabilitation procedure, the patient's blood pressure was very unstable,
      fluctuating between high (210/110 mmHg) and low (110/70 mmHg) values accompanied
      by a fainting sensation. A second stroke of left hemiplegia took place 1 month
      later. Afterwards, his condition worsened to tetraplegia with dysarthria. Three
      months later, lung cancer with multiple metastasis including his left neck was
      found and he died from adynamic ileus 6 months after the onset of the present
      illness. Autopsy revealed nearly complete atheromatous obstruction and more than
      50% stenosis, respectively, of his right common and internal/external carotid
      arteries. His intracranial arterial trunks and main branches were all patent with
      localized atherosclerosis of only moderate degree. The pathology of the brain
      existed predominantly in the right hemisphere in the border zone area between the
      anterior and middle cerebral arteries systematically with numerous disseminated
      foci of complete or incomplete necrosis, white matter and gray matter being
      involved independently. Involvement of centrum semiovale white matter is more
      extensive and intensive than that of gray matter. Of the gray matter, cerebral
      cortex as well as striatum, periventricular (the third ventricle) gray and
      cerebellar cortex was involved. The specific characteristic topography and
      distribution of the lesions together with their histopathology are described in
      detail with illustration. It is concluded that this case represents an
      outstanding example of hemodynamic cerebral circulatory insufficiency doubly
      caused by hemilateral carotid artery stenosis and repeated episodes of systemic
      hypotension.

PMID- 11837535
TI  - A case of non-functioning pituitary adenoma with Cushing's syndrome upon
      recurrence.
AB  - A 49-year-old woman presented with left visual disturbance. No signs of Cushing's
      disease were evident. Basal levels of serum cortisol and plasma
      adrenocorticotropic hormone (ACTH) were 16.8 microg/dL and 66.0 pg/mL,
      respectively. MRI demonstrated an irregularly shaped large pituitary tumor, and
      the patient then underwent transsphenoidal surgery. By light microscopy the tumor
      represented a chromophobic adenoma with a few of the adenoma cells showing
      immunoreactivity for ACTH. On the basis of clinical and light microscopic
      examinations, the diagnosis of silent corticotroph adenoma was made. Electron
      microscopy, however, demonstrated the honeycomb Golgi complex that has been
      reported as a typical finding of gonadotroph adenomas. MRI taken 7 months after
      the first operation revealed adenoma regrowth. Transcranial surgery was
      performed, and histology demonstrated a chromophobic pituitary adenoma with most
      cells immunopositive for ACTH. She was treated with gamma knife postoperatively.
      Three months later, MRI revealed remarkable shrinkage of the adenoma, but she
      developed typical signs and symptoms of Cushing's disease. Thus, the hormone
      immunostaining and biological activity of pituitary adenomas may change with
      time.

PMID- 11837536
TI  - An atypical case of sporadic Creutzfeldt-Jakob disease with Parkinson's disease.
AB  - We report here an autopsy case of a 64-year-old female with slowly progressive
      dementia and parkinsonism in a 4-year-long clinical course. Post-mortem
      examination revealed a severely atrophic brain with spongiform degeneration,
      neuronal loss and gliosis in the gray matter. Many prion protein plaque deposits
      were present in the occipital lobe, amygdala and cerebellum. Additionally, Lewy
      bodies were observed in the brainstem. Prion protein gene analysis of the patient
      revealed polymorphism at the codon-129 valine heterozygote. This genotype is
      known to sometimes accompany a missense mutation of the gene in uncommon
      hereditary prion diseases, but no mutation was found in the open reading frame.
      Thus, it might be suggested that this case showed simultaneously the features of
      both sporadic Creutzfeldt-Jakob disease (CJD) with codon-129 valine and
      Parkinson's disease. However, the predisposing factors for contracting both
      diseases simultaneously remain to be determined, because the incidence of
      Parkinson's disease accompanied by CJD is very low.

PMID- 11837537
TI  - Gamma knife radiosurgery for neuroepithelial tumors: radiological and
      histological changes.
AB  - Gamma knife radiosurgery (RS) has been introduced as a modern therapy for brain
      tumors. However, the effects of RS for neuroepithelial tumors are still obscure.
      The present study investigates the radiological and histological changes after RS
      to elucidate the biological effect. There were seven cases (two males and five
      females), ranging from 4 to 71 years with a mean age of 33 years. Two cases were
      located in the brainstem, another two in the cerebellum, and one each in the
      thalamus, the hypothalamus, and the frontal lobe. Histologically, two cases had
      gangliogliomas, four astrocytomas (1 pilocytic, 1 fibrillary, 2 anaplastic), and
      one glioblastoma. RS was performed after surgery with a central dose of 30-36 Gy.
      All cases were evaluated radiologically on MRI before and after RS. Four cases (3
      astrocytomas and 1 glioblastoma) which neurologically deteriorated after RS were
      reoperated. These cases were examined using HE and immunohistochemical studies
      with antibodies of CD34, alpha-smooth muscle actin (SMA), p53, p21 and MIB-1 on
      the sections before and after RS. MRI demonstrated perifocal edema and
      intratumoral hypointensity on T2 weighted imaging (T2WI), suggesting
      radionecrosis in most of the cases within 6 months after RS. In the central part
      of the RS, destructive changes were observed in the tumor cells and endothelial
      cells: decrease in the tumor cell population, coagulation necrosis, and fibrinoid
      degeneration of vascular walls were revealed. In the peripheral part, however,
      some tumors contained viable tumor cells intermingled with blood vessels showing
      endothelial and pericytic proliferations. The increase of MIB-1 staining index
      was found in only one case. The p21 immunoreactivity was increased in endothelial
      cells, although the p53 immunoreactivity was unchanged. These results suggested
      that radionecrosis occurred earlier and more frequently in neuroepithelial tumors
      after RS than after conventional radiation.

PMID- 11837538
TI  - Effects of stereotactic radiosurgery on metastatic brain tumors of various
      histopathologies.
AB  - Although reports have been published describing clinical results in a large
      series of patients with metastatic brain tumors treated by stereotactic
      radiosurgery (SRS), clinical neuropathological correlation has rarely been
      available. The present paper describes three autopsy cases and one surgical case
      treated with linear accelerator based radiosurgery. The cases comprised a lung
      cancer, a rectal cancer, an osteosarcoma, and a malignant melanoma. Histological
      sections of each tumor were analyzed by light microscopy based on the Ohosi and
      Shimosato's histopathological classification of the effects of radiation therapy.
      In three cases (pulmonary squamous cell carcinoma, rectal adenocarcinoma and
      osteosarcoma), a large area of the tumors consisted of coagulation necrosis and
      non-viable tumor cells, while coagulation necrosis and non-viable tumor cells
      comprised a very small part of the malignant melanoma. Histopathological type of
      the metastatic brain tumor may be one of the factors influencing outcome after
      SRS.

PMID- 11837539
TI  - The cellular pathology of Parkinson's disease.
AB  - Parkinson's disease (PD) is a common neurodegenerative disorder of unknown cause
      that occurs in adults. The presence of Lewy bodies (LB) in association with nerve
      cell loss in the substantia nigra and various other regions of the nervous system
      is a diagnostic hallmark of the disease. In 1997, a mutation was identified in
      the alpha-synuclein gene in families with autosomal dominant PD. Subsequent
      immunohistochemical studies have revealed that all of the LB in familial and
      sporadic PD contain the gene product alpha-synuclein: abnormal filaments that
      constitute LB were clearly recognized by antibodies against alpha-synuclein.
      Moreover, it was shown that the glial cells, both astrocytes and
      oligodendrocytes, are also affected by alpha-synuclein pathology. Recently, a
      novel protein, synphilin-1, has been identified that interacts with alpha
      synuclein. Interestingly, synphilin-1 immunohistochemistry has demonstrated that
      this protein is present in the central core of classical (brainstem) LB, which
      are composed mainly of densely packed vesicular structures. The role of both
      alpha-synuclein and synphilin-1 in normal conditions has yet to be clarified.

PMID- 11837540
TI  - Neurotoxicity of MPTP.
AB  - After the discovery of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), we
      acquired a good animal model of Parkinson's disease. The extraordinary recent
      growth in knowledge using MPTP parkinsonism has fostered increased understanding
      of Parkinson's disease. In the present paper, the discovery of MPTP and the
      biochemical, pathological, and clinical findings of MPTP parkinsonism are first
      reviewed briefly. Next, using MPTP parkinsonism, unresolved issuses such as the
      apoptosis of MPTP, levodopa toxicity, and neuroprotective effects of monoamine
      oxidase inhibitors or dopamine agonists are discussed. Finally, environmental
      factors such as the etiology of Parkinson's disease are examined. Some genetic
      factors that lead to familial Parkinson's disease have recently been reported,
      but most cases of Parkinson's disease are sporadic. Recent epidemiological
      evidence emphasizes an etiological relation of 18th and 19th century
      industrialization to Parkinson's disease. Man-made toxins, such as industrial
      chemicals and herbicides/pesticides, have been suggested to increase the risk of
      developing Parkinson's disease. I would like to highlight the significance of re
      examination of environmental factors in the etiology of Parkinson's disease.

PMID- 11837541
TI  - Cerebral malformation in a child with profound psychomotor retardation and
      infantile spasms.

PMID- 11837542
TI  - A 63-year-old man presenting with a chronic progressive course of spinal cord and
      brainstem symptoms.

PMID- 11837543
TI  - Progressive dementia with character change in an 84-year-old man.

PMID- 11837544
TI  - Brain tumor of the right frontal lobe.

PMID- 11837545
TI  - Pitfalls associated with commonly used methods for pharmacoeconomic analyses.
AB  - Demonstrating the economic value of treatment has become an important objective
      of many clinical trials. Awareness of the limitations of the methods used in
      pharmacoeconomic studies of infectious diseases will help in understanding why
      improved methods are needed to adequately describe the costs associated with
      infectious episodes. Current analyses generally consider three levels of cost and
      use three methods to determine costs associated with an infectious episode.
      However, these costs and the methods for obtaining them may not be appropriate in
      all studies. Future pharmacoeconomic research needs to adhere to established
      principles but embrace new methodologies to improve the validity and usefulness
      of these studies.

PMID- 11837546
TI  - The dynamics of health care resource utilization.
AB  - Many pharmacoeconomic studies suffer from issues relating to the sensitivity of
      data and ability to accurately determine treatment-related costs. In addition,
      cost data generally are treated as static or constant variables. Our goal was to
      develop an approach to cost analysis that would allow us to appreciate the
      dynamic nature of health care resource utilization. By collecting detailed cost
      data on a daily basis and focusing on a narrow interval encompassing the
      infectious process, we were able to detect changes in resource utilization
      associated with management of the infectious process. This method also allowed us
      to assess and compare the dynamics of resource utilization among various patient
      groups.

PMID- 11837547
TI  - Approaches to analysis of length of hospital stay related to antibiotic therapy
      in a randomized clinical trial: linezolid versus vancomycin for treatment of
      known or suspected methicillin-resistant Staphylococcus species infections.
AB  - As length of hospital stay (LOS) represents about 70-90% of the total cost of
      treating serious infections, it represents a key variable in analyzing the health
      economic differences between treatments for hospitalized patients. In a
      retrospective analysis using LOS data from a multinational, randomized, phase III
      clinical trial, we examined two methods (the log-logistic model and Kaplan-Meier
      survival function) and three approaches (unadjusted total LOS, total LOS adjusted
      for nontreatment factors, and adjusted LOS based on antibiotic treatment [the
      antibiotic treatment LOS]) for estimating antibiotic treatment effect on LOS and
      determined if these approaches could reduce the variation in LOS and control for
      the imbalance between treatment groups. The trial enrolled patients who were
      hospitalized with known or suspected Staphylococcus species infections who
      received at least one dose of linezolid or vancomycin (intent-to-treat sample)
      and who continued taking the study drug for at least 7 days (clinically evaluable
      sample). In the intent-to-treat sample, the linezolid group had a 2- (unadjusted)
      or 4-day (adjusted for nontreatment factors) shorter LOS at the 25th percentile;
      a 1- or 2-day advantage, respectively, at the 50th percentile (median); and a 0.6
      or 1.6-day mean LOS advantage, compared with the vancomycin group. With the
      antibiotic treatment LOS approach, the linezolid group had mean and median LOS
      reductions comparable to or greater than those seen in the nontreatment-factor
      adjusted results. Results for the clinically evaluable sample were similar to
      those of the intent-to-treat sample, but the differences between the treatment
      groups were greater. Linezolid-treated patients had significant LOS reductions
      that otherwise would be masked without the use of more appropriate, but less
      commonly used, methods.

PMID- 11837548
TI  - Use of insurance claims data to assess outpatient antimicrobial therapy for gram
      positive infections.
AB  - With the increasing frequency of antibiotic-resistant gram-positive infections in
      the United States, many patients are being treated outside the hospital setting.
      The majority of studies on the cost of outpatient antimicrobial therapy involve
      retrospective medical record review or prospective data collection. These methods
      tend to be expensive and time consuming, and often fail to produce a sufficiently
      large sample size. Analysis of insurance claims data offers a convenient approach
      for studying the costs associated with outpatient therapy for gram-positive
      infections. To demonstrate this approach, a study of the cost of intravenous
      vancomycin home care therapy was conducted using claims data from a large
      insurance company.

PMID- 11837549
TI  - Cost perspectives for outpatient intravenous antimicrobial therapy.
AB  - Intravenous antimicrobial therapy often continues after a patient is discharged
      from the hospital or it begins in the outpatient setting. Reimbursement for this
      therapy varies by payer. The United States Outpatient Parenteral Antibiotic
      Therapy (OPAT) Outcomes Registry is a valuable resource for quantifying cost by
      payer, as well as for describing practice patterns and adverse events related to
      intravenous antimicrobial therapy. To describe the reimbursement structure and
      cost of intravenous vancomycin home care therapy for four different types of
      payers, a survey of home infusion companies was done. Also surveyed were infusion
      programs participating in the OPAT Outcomes Registry, representing four different
      types of payers, to determine the cost of outpatient intravenous therapy. A
      retrospective cohort study of these infusion programs was conducted to describe
      practice patterns and to identify adverse events that resulted from intravenous
      vancomycin. We found that the cost of outpatient therapy was substantial,
      although nonuniform, across payer types. Alternative outpatient therapies
      associated with lower risks for adverse events and lower costs should be
      considered.

PMID- 11837550
TI  - Pharmacoeconomic studies of asthma controller drugs: marketing gimmick or icing
      on the cake?

PMID- 11837551
TI  - Clinical pharmacy services, hospital pharmacy staffing, and medication errors in
      United States hospitals.
AB  - The direct relationships and associations among clinical pharmacy services,
      pharmacist staffing, and medication errors in United States hospitals were
      evaluated. A database was constructed from the 1992 National Clinical Pharmacy
      Services database. Both simple and multiple regression analyses were employed to
      determine relationships and associations. A total of 429,827 medication errors
      were evaluated from 1081 hospitals (study population). Medication errors occurred
      in 5.22% of patients admitted to these hospitals each year. Hospitals experienced
      a medication error every 22.04 hours (every 19.13 admissions). These findings
      suggest that at minimum, 90,895 patients annually were harmed by medication
      errors in our nation's general medical-surgical hospitals. Factors associated
      with increased medication errors/occupied bed/year were drug-use evaluation
      (slope = 0.0023476, p=0.006), increased staffing of hospital pharmacy
      administrators/occupied bed (slope = 29.1972932, p<0.001), and increased staffing
      of dispensing pharmacists/occupied bed (slope = 19.3784148, p<0.001). Factors
      associated with decreased medication errors/occupied bed/year were presence of a
      drug information service (slope = -0.1279301, p<0.001), pharmacist-provided
      adverse drug reaction management (slope = -0.3409332, p<0.001), pharmacist
      provided drug protocol management (slope = -0.3981472, p=0.013), pharmacist
      participation on medical rounds (slope = -0.6974303, p<0.001), pharmacist
      provided admission histories (slope = -1.6021493, p<0.001), and increased
      staffing of clinical pharmacists/occupied bed (slope = -9.5483813, p<0.001). As
      staffing increased for clinical pharmacists/occupied bed from the 10th percentile
      to the 90th percentile, medication errors decreased from 700.98 +/- 601.42 to
      245.09 +/- 197.38/hospital/year, a decrease of 286%. Specific increases or
      decreases in yearly medication errors associated with these clinical pharmacy
      services in the 1081 study hospitals were drug-use evaluation (21,372 more
      medication errors), drug information services (26,738 fewer medication errors),
      adverse drug reaction management (44,803 fewer medication errors), drug protocol
      management (90,019 fewer medication errors), medical round participation (42,859
      fewer medication errors), and medication admission histories (17,638 fewer
      medication errors). Overall, clinical pharmacy services and hospital pharmacy
      staffing variables were associated with medication error rates. The results of
      this study should help hospitals reduce the number of medication errors that
      occur each year.

PMID- 11837552
TI  - Effect of renal impairment on the pharmacokinetics of a single oral dose of
      tibolone 2.5 mg in early postmenopausal women.
AB  - STUDY OBJECTIVE: To determine the influence of renal function on the
      pharmacokinetics of tibolone and its primary metabolites, delta4-tibolone, 3alpha
      hydroxytibolone, and 3beta-hydroxytibolone. DESIGN: Open-label, single-center,
      single-dose study SETTING: Drug research center, Balatonfured, Hungary. SUBJECTS:
      Twenty-four postmenopausal women aged 45-65 years. INTERVENTION: Subjects were
      assigned to one of four groups based on their renal function, as assessed by
      glomerular filtration rate (normal to severely impaired), and received a single
      dose of tibolone 2.5 mg. Pharmacokinetic parameters of tibolone and its primary
      metabolites were derived from blood samples taken at predefined intervals for up
      to 48 hours after tibolone administration. Pharmacokinetic parameters were
      calculated using standard noncompartmental methods and compared by analysis of
      covariance. MEASUREMENTS AND MAIN RESULTS: Pharmacokinetic parameters of tibolone
      and its primary metabolites were similar in subjects with normal to severely
      impaired renal function. Pharmacokinetic profiles of tibolone and its metabolites
      were independent of the degree of renal impairment. CONCLUSION: Pharmacokinetic
      parameters of tibolone were not affected by varying degrees of renal function.

PMID- 11837553
TI  - Effect of food on everolimus absorption: quantification in healthy subjects and a
      confirmatory screening in patients with renal transplants.
AB  - STUDY OBJECTIVE: To quantify the influence of a high-fat meal on the oral
      bioavailability of the immunosuppressant everolimus in a single-dose study in
      healthy subjects and to confirm the results in a small food-effect screening
      assessment in patients with renal transplants who were receiving multiple-dose
      everolimus. DESIGN: Randomized, open-label, crossover, single-dose study and
      confirmatory screening. SETTING: Phase 1 unit for the single-dose study and two
      German hospitals for the patient screening. SUBJECTS: Twenty-four healthy male
      volunteers; six clinically stable patients with renal transplants who were
      originally part of a phase I dose-escalation study. INTERVENTION: The 24 healthy
      men received everolimus 2 mg orally under fasting conditions and after a high-fat
      meal. The six patients received everolimus 2.5 mg/day orally, in addition to
      cyclosporine and prednisone. On two occasions, a pharmacokinetic profile was
      obtained over the dosing interval after drug administration under fasting
      conditions and after a high-fat meal in a randomized sequence. MEASUREMENTS AND
      MAIN RESULTS: In the single-dose study in healthy subjects, a high-fat meal
      delayed everolimus time to maximum concentration (Tmax) by a median 1.25 hours,
      reduced peak blood concentration (Cmax) by 60%, and reduced area under the
      concentration-time curve (AUC) by 16%. In the multiple-dose screening in patients
      with renal transplants, a high-fat meal delayed Tmax by a median 1.75 hours and
      reduced Cmax by 53% and AUC by 21%. Everolimus trough levels showed no food
      effect, whereas the peak-trough fluctuation was dampened by 52%. CONCLUSIONS: A
      high-fat meal modestly reduced everolimus AUC. To minimize longitudinal
      variability in exposure, everolimus should be administered consistently either
      with food or without food.

PMID- 11837554
TI  - Effect of a high-fat meal on the pharmacokinetics of the des-F(6)-quinolone BMS
      284756.
AB  - STUDY OBJECTIVE: To evaluate the effects of a high-fat meal on the systemic
      exposure of oral BMS-284756. DESIGN: Open-label, randomized, two-way crossover
      study. SETTING: Clinical research facility. SUBJECTS: Fourteen healthy
      individuals. INTERVENTIONS: Participants received two single 400-mg doses of BMS
      284756, separated by at least 1 week. One dose was given while participants were
      fasting, and one dose was given within 5 minutes of consumption of a high-fat
      meal. MEASUREMENTS AND MAIN RESULTS: Serial blood samples were collected, and
      plasma samples were analyzed for BMS-284756 using a validated liquid
      chromatography with tandem mass spectrometry detection method. Maximum plasma
      concentration and area under the plasma concentration-time curve (AUC) after the
      high-fat meal were 19% and 11% lower, respectively, than those in the fasted
      state. The 90% confidence intervals for the ratios of means (0.71-0.94 and 0.85
      0.93, respectively) satisfied predefined equivalence criteria. Equivalence of the
      AUC values for BMS-284756 in fed and fasted individuals indicates that the
      presence of food should not affect the efficacy of this drug. CONCLUSION: Single
      doses of BMS-284756 were safe and well tolerated and may be taken without regard
      to meals.

PMID- 11837555
TI  - Economic impact of asthma therapy with fluticasone propionate, montelukast, or
      zafirlukast in a managed care population.
AB  - STUDY OBJECTIVE: To compare asthma-related health care expenditures among
      patients newly prescribed fluticasone propionate 44 or 110 microg, montelukast 5
      or 10 mg, or zafirlukast 20 mg. DESIGN: Retrospective cohort analysis of medical
      and pharmacy claims. SETTING: University-affiliated health outcomes research
      center. PATIENTS: Seven hundred eighty-one patients (aged > or = 4 yrs) with
      asthma treated with controller therapy for 9 months (postindex period), with no
      claim for an inhaled corticosteroid or leukotriene modifier in the previous 9
      months (preindex period). INTERVENTION: Asthma-related medical and pharmacy data
      from insurance claims of four managed care plans (two Northeastern, one
      Midwestern, and one Western) were tabulated over the pre- and postindex periods.
      MEASUREMENTS AND MAIN RESULTS: Numbers of patients identified were 284 beginning
      fluticasone propionate; 302, montelukast; and 195, zafirlukast. Fluticasone
      propionate treatment was associated with significantly (p<0.001) lower risk
      adjusted asthma-related charges compared with montelukast and zafirlukast
      treatment: $528, $967, and $1359, respectively In this cohort, fluticasone
      propionate also was associated with fewer hospitalizations, less need for
      additional controller agents, and longer maintenance on the index drug compared
      with montelukast and zafirlukast. CONCLUSIONS: Based on these real-world data, as
      well as established national and international asthma guidelines, consideration
      should be given to inhaled corticosteroid therapy, particularly fluticasone
      propionate, for first-line, long-term effective management of asthma.

PMID- 11837557
TI  - Hemorrhagic complications of enoxaparin and aspirin in patients with kidney
      transplants.
AB  - STUDY OBJECTIVE: To evaluate the frequency of early posttransplant hemorrhagic
      complications in patients with kidney and kidney-pancreas transplants who
      received thromboprophylaxis with enoxaparin and aspirin. DESIGN: Retrospective
      chart review. SETTING: University-based tertiary care center. PATIENTS: Thirteen
      patients who had received enoxaparin within 10 days of kidney or kidney-pancreas
      transplantation. INTERVENTION: Medical records were reviewed, and data from
      patients who had received low-dose aspirin 81 mg once/day and enoxaparin within
      10 days of transplantation were collected. MEASUREMENTS AND MAIN RESULTS: Major
      bleeding events were defined as intracranial or retroperitoneal bleeding, or a
      decrease in hemoglobin of greater than 2 g/dl that was confirmed on repeat
      evaluation. Nine (69%) of the 13 patients had confirmed major bleeding events and
      required blood transfusions. Six of the nine patients had elevated serum
      creatinine levels. CONCLUSION: The combination of enoxaparin and low-dose aspirin
      early after kidney or kidney-pancreas transplantation was associated with a high
      frequency of hemorrhagic events. Further evaluation is needed to determine the
      safety of enoxaparin in combination with aspirin after transplantation.

PMID- 11837556
TI  - Pharmacokinetics of levofloxacin during continuous venovenous hemodiafiltration
      and continuous venovenous hemofiltration in critically ill patients.
AB  - STUDY OBJECTIVE: To assess the pharmacokinetics of levofloxacin during continuous
      venovenous hemodiafiltration (CVVHDF) and continuous venovenous hemofiltration
      (CVVH). DESIGN: Nonrandomized pharmacokinetic evaluation. SETTING: University
      surgical intensive care unit. PATIENTS: Six critically ill patients.
      INTERVENTION: Five patients received levofloxacin 500 mg/day and one patient
      received levofloxacin 125 mg/day All patients received continuous renal
      replacement therapy: CVVHDF on day 1 and CVVH on day 2, using an acrylonitrile
      hollow-fiber 0.9-m2 filter, constant blood flow rate of 90 ml/minute,
      substitution flow rate of 1 L/hour predilution, and dialysate flow rate of 1
      L/hour (CVVHDF). MEASUREMENTS AND MAIN RESULTS: Serum, ultrafiltrate, and
      dialysate concentrations of levofloxacin were determined by high-performance
      liquid chromatography. Extracorporeal clearance was 26.05 +/- 4.66 ml/hour during
      CVVHDF and 15.71 +/- 2.73 ml/hour during CVVH (p<0.05). Elimination half-life was
      28.08 +/- 4.5 hours and 45.9 +/- 17.7 hours, and distribution volume was 1.51 +/-
      0.52 L/kg and 1.42 +/- 0.42 L/kg for CVVHDF and CVVH, respectively. Saturation
      was 0.76 +/- 0.13 for CVVHDF versus a sieving coefficient of 0.77 +/- 0.16 for
      CVVH. CONCLUSION: Marked extracorporeal elimination of levofloxacin occurs,
      requiring a dosage adjustment that can be calculated from the characteristics of
      CVVH and CVVHDF.

PMID- 11837558
TI  - Parenteral nutrition-associated liver complications in children.
AB  - Parenteral nutrition is a life-saving therapy for patients with intestinal
      failure. It may be associated with transient elevations of liver enzyme
      concentrations, which return to normal after parenteral nutrition is
      discontinued. Prolonged parenteral nutrition is associated with complications
      affecting the hepatobiliary system, such as cholelithiasis, cholestasis, and
      steatosis. The most common of these is parenteral nutrition-associated
      cholestasis (PNAC), which may occur in children and may progress to liver
      failure. The pathophysiology of PNAC is poorly understood, and the etiology is
      multifactorial. Risk factors include prematurity, long duration of parenteral
      nutrition, sepsis, lack of bowel motility, and short bowel syndrome. Possible
      etiologies include excessive caloric administration, parenteral nutrition
      components, and nutritional deficiencies. Several measures can be undertaken to
      prevent PNAC, such as avoiding overfeeding, providing a balanced source of
      energy, weaning parenteral nutrition, starting enteral feeding, and avoiding
      sepsis.

PMID- 11837559
TI  - Combination therapy with inhaled long-acting beta2-agonists and inhaled
      corticosteroids: a paradigm shift in asthma management.
AB  - Long-acting inhaled beta2-agonists and inhaled corticosteroids are classes of
      drugs with different mechanisms of action that are commonly used to provide
      effective long-term control of persistent asthma. Scientific and clinical data
      support the complementary mechanisms of action of the inhaled corticosteroids and
      the long-acting beta2-agonists in achieving a superior level of asthma control.
      In addition, evidence supports significant reductions in exacerbations and
      effective control of airway inflammation with an inhaled corticosteroid and a
      long-acting beta2-agonist versus higher dosages of inhaled corticosteroids or
      combinations of other therapeutic agents with an inhaled corticosteroid. Finally,
      there are distinct economic advantages to combining an inhaled corticosteroid and
      a long-acting beta2-agonist in the treatment of asthma relative to other
      treatment regimens.

PMID- 11837560
TI  - Therapy with macrolides in patients with cystic fibrosis.
AB  - Cystic fibrosis affects 1/2500 individuals and is the most common lethal
      autosomal recessive disease in people of northern European descent. It is
      characterized by chronic infections with mucoid Pseudomonas aeruginosa and
      progressive deterioration of respiratory function. Much research has focused on
      the inflammatory component of the disease. Macrolide antibiotics are postulated
      to suppress inflammatory mediators and interfere with biofilm formation produced
      by P. aeruginosa. In vitro studies show promising results, and a limited number
      of human studies reported improvements in respiratory function with the drugs.
      Macrolide antibiotics are generally safe and well tolerated and may prove to be
      effective in patients with cystic fibrosis.

PMID- 11837561
TI  - Management of opioid-induced gastrointestinal effects in patients receiving
      palliative care.
AB  - Opioid-induced gastrointestinal side effects, namely, nausea and constipation,
      are bothersome yet often easy to manage. Due to their widespread frequency, it is
      imperative that prophylactic and treatment modalities be understood. Although
      many pharmacotherapeutic agents are available with which to prevent or treat
      these side effects, few randomized, placebo-controlled studies have been
      conducted in terminally ill patients, thus limiting most treatment decisions to
      empiric therapies based on extrapolated data. A strong understanding of the
      pathophysiology of the sequelae is therefore paramount. Common agents
      administered for nausea are butyrophenones, phenothiazines, metoclopramide, and
      serotonin-receptor antagonists. Those given to manage constipation are stimulant
      laxatives and stool softeners, individually or in combination.

PMID- 11837562
TI  - Pharmacist impact on posttraumatic seizure prophylaxis in patients with head
      injury.
AB  - Phenytoin is the most commonly administered antiepileptic agent for the
      prevention of early (< or = 7 days) posttraumatic seizures. Use of the agent,
      however, requires strict monitoring due to its narrow target range and nonlinear
      pharmacokinetics. The impact of a clinical pharmacist participating in the care
      of patients with head injury on posttraumatic seizure prophylaxis with regard to
      phenytoin dosing and monitoring, cost avoidance, and patient outcome, was
      measured retrospectively. Parameters from time periods before (BP) and after (AP)
      a clinical pharmacist participated in patient care were compared. The average
      number of days that phenytoin was given was 13.4 (BP) and 7.6 (AP), and the
      duration of phenytoin prophylaxis was 7 days or less in 35% and 65% of patients,
      respectively. The average number of phenytoin levels drawn from each patient was
      10.3 (BP) and 3.4 (AP). Seizures occurred in 4.7% (BP) and 1.5% (AP) of patients.
      A cost savings of approximately $28,000 was observed for the AP group. A clinical
      pharmacist reduced the use of posttraumatic seizure prophylaxis and associated
      costs without jeopardizing patient outcomes.

PMID- 11837563
TI  - Evaluation of the use of complementary and alternative medicine in the largest
      United States-Mexico border city.
AB  - STUDY OBJECTIVE: To evaluate the use of complementary and alternative medicine
      (CAM) in the El Paso, Texas, region. DESIGN: Prospective observational study
      conducted from April-October 2000. SETTING: Several hospitals and clinics.
      SUBJECTS: Five hundred forty-seven participants. INTERVENTION: Semi-structured
      interview with a bilingual questionnaire. MEASUREMENTS AND MAIN RESULTS:
      Complementary and alternative medicine was used in 77% of our population. The
      most common CAM providers were massage therapists (19.4%) and herbalists (12.4%).
      The most common herbal or home remedies were chamomile (13.1%) and aloe vera
      (8.5%). The most common nutritional or commercial products were multivitamins
      (16%), ginseng (3.6%), and ginkgo biloba (2.8%). We identified 599 CAM usages
      that could result in drug interactions, disease interactions, or adverse
      reactions. CONCLUSIONS: A wide range of CAM use was documented in this study. Our
      results indicate that Hispanics in this area use CAM at a higher rate than
      national trends. Many of these therapies can adversely affect a variety of
      disease states and drug therapies.

PMID- 11837564
TI  - Warfarin-associated bleeding complication saved life.
AB  - A 62-year-old Caucasian man with atrial fibrillation who was taking warfarin
      reported an episode of hematochezia; his international normalized ratio (INR) was
      1.74. His weekly warfarin dose was increased by approximately 5%, and he was
      given three fecal occult blood cards. At follow-up 1 week later, the patient
      denied any episodes of hematochezia. His INR was 1.69 despite the increased
      warfarin dosage. One of the occult blood cards showed a positive result, and
      colonoscopy revealed a 5-cm lesion, identified as Dukes' A adenocarcinoma.
      Warfarin-associated bleeding generally is considered deleterious; however, in our
      patient it unmasked an early stage of colon cancer and thus may have saved the
      patient's life. Although minor gastrointestinal bleeding is common among patients
      taking anticoagulants, all patients should be fully evaluated because the source
      of hemorrhage may be malignant.

PMID- 11837565
TI  - Confessions of a fly-fisherman and sometime drug company courtesan.

PMID- 11837566
TI  - A possible mechanism of mast cell proliferation in mastocytosis.
AB  - The abnormality in mastocytosis is the excessive accumulation of mast cells in
      the affected tissue. The growth and differentiation of human mast cells are quite
      dependent on stem cell factor (SCF), the ligand for the protein products of c
      kit. Recent studies have demonstrated that all adult patients examined so far
      carry c-kit point mutations, leading to SCF-independent autophosphorylation of
      the receptor and autonomous cell growth. On the other hand, typical pediatric
      patients have been found to bear no activating Asp816Val mutation in c-kit.
      Although most mastocytosis patients are children, the mechanism by which mast
      cells proliferate in these pediatric patients remains unclear. Recently, were
      reported that human mast cells obtained from adult skin could dramatically
      proliferate when cultured with SCF. From these experimental results, it is
      speculated that local excessive production of SCF results in the mast cell
      proliferation in pediatric patients.

PMID- 11837567
TI  - Kikuchi-Fujimoto disease: an overview.

PMID- 11837568
TI  - Clinical course of 44 cases of localized type vitiligo.
AB  - Vitiligo is often classified into three types, generalized, segmental, and
      localized, on the basis of their distribution pattern. It is also classified into
      type A (non-dermatomal or non-segmental) and type B (dermatomal or segmental)
      vitiligo on the basis of both the distribution pattern and physiological
      function. The natural courses of type A and type B vitiligo are characteristic
      and quite different from each other. Whereas type A vitiligo appears at any age
      and progresses throughout the patient's life span, type B vitiligo affects the
      young and stabilizes within a few years. Segmental type vitiligo corresponds to
      type B, and generalized type vitiligo is the late stage of type A. However, no
      one has observed the course and character of localized type vitiligo, and its
      nosological position in A/B classification is unclear. We followed 44 cases of
      localized type vitiligo for periods of 6 months to 8 years. In 3 of the 44
      patients, new white patches developed within the same dermatome as their affected
      areas in the first 12 months and stabilized in a short period. Therefore, these
      patients were diagnosed as type B vitiligo. In 15 patients, vitiligo developed in
      other dermatomal areas; the earliest case at 9 months, and others later on. The
      new white patches continue to develop for a long period, so these patients were
      diagnosed with type A vitiligo. In 26 of the 44 patients, the vitiligo remained
      localized within the period of observation. It is concluded that most localized
      type vitiligo is the early stage of type A, but a small number of cases belong to
      the early stage of type B.

PMID- 11837569
TI  - Minocycline effectively reduces acid producted by Propionibacterium granulosum.
AB  - We studied the effects of minocycline on Propionibacterium granulosum. P.
      granulosum lipase activity was detected from acne lesions. Production of
      propionic and butyric acids by P. granulosum was well suppressed by all tested
      media with added minocycline; the higher the concentration of minocycline in the
      medium, the less of these acids was produced. It appeared that the decrease in
      these acids due to minocycline was greater in P. granulosum than in P. acnes.
      Although the influence of P. granulosum on acne lesions might be feebler than
      that of P. acnes, we should not neglect its presence. More research is needed to
      elucidate the relationship between the two species in acne lesions.

PMID- 11837570
TI  - Therapeutic effects of antibacterial treatment for intractable skin diseases in
      Helicobacter pylori-positive Japanese patients.
AB  - In order to understand the pathogenic relationship between Helicobacter pylori
      (H. pylori) and skin diseases, we examined the serum levels of IgG antibody
      against H. pylori and then performed gastroscopic examinations in Japanese
      patients with chronic skin diseases. These H. prylori-positive patients were
      treated with antibacterial eradication therapy, and therapeutic efficacy was
      evaluated. A total of 198 patients who were resistant to conventional therapies
      were randomly selected. They included 50 cases with chronic urticaria, 32 with
      pruritus cutaneous, 74 with atopic dermatitis, 15 with nummular dermatitis, 17
      with prurigo chronica multiformis, 6 with psoriasis vulgaris, and 4 with
      erythroderma. Positive anti-H. pylori antibody was detected in 102 out of these
      198 patients; more than half of the ones with chronic urticaria, pruritus
      cutaneous, nummular dermatitis, and prurigo chronica multiformis had positive
      antibodies. Gastroscopy was then performed in 48 cases with positive antibodies.
      Eradication therapy was effective in 60% of the patients with chronic urticaria,
      in 58% with pruritus cutaneous, in 54% with nummular dermatitis, and in 50% with
      prurigo chronica multiformis. In chronic skin diseases, persistent infection with
      H. pylori may be an eruption trigger and may cause deterioration of the disease
      into an in tractable and chronic form.

PMID- 11837571
TI  - A case of cellular schwannoma of the skin presenting as a large ulcerated tumor
      on the ankle.
AB  - Cellular schwannoma (CS) is a rare, benign, nerve sheath tumor. It is slowly
      growing and painless, and it shows a predilection for the paravertebral region of
      the mediastinum and the retroperitoneum. CS rarely occurs in the skin. It has
      more cellular and more atypical cytological features than ordinary schwannoma but
      follows a benign clinical course. The key histological feature is a distinct
      predominance of cellular Antoni A tissue. Herein we report a case of CS
      presenting as a 5 x 5 x 3 cm, ulcerated and protruding tumor on the left ankle
      and describe its indolent clinical course.

PMID- 11837572
TI  - Docetaxel induced durable response in advanced extramammary Paget's disease: a
      case report.
AB  - The patient was a 54-year-old Japanese man with a seven-month history of an
      eroded lesion on the scrotum. Skin biopsy confirmed the diagnosis of extramammary
      Paget's disease, and a CT scan revealed multiple metastases to the lymph nodes
      along the iliac artery and aorta. The patient underwent combination chemotherapy
      with mitomycin C, epirubicin, vincristine, cisplatin, and 5-fluorouracil. After
      two courses of the regimen, the primary lesions on the scrotum regressed,
      however, the lymph node metastases did not respond. A regimen of continuous
      administration of low-dose cisplatin and 5-fluorouracil was not effective for the
      metastases either. Hence, administration of docetaxel at a dose of 60 mg/m2/every
      four weeks was started. After two courses, the lymph node metastases decreased by
      75% compared to the pre-treatment size, and the effect was judged a partial
      response. The major toxicities were neutropenia, alopecia, pitting edema, and
      facial erythema, but these were tolerable. Five courses of this regimen were
      followed by four courses of weekly administration of 25 mg/m2 docetaxel. The
      partial response persisted for more than 12 months and the patient was able to
      enjoy daily life. Docetaxel may be an effective drug for patients with advanced
      extramammary Paget's disease.

PMID- 11837573
TI  - Protruding tumorous angiolymphoid hyperplasia with eosinophilia (ALHE) of the
      scalp accompanied by arterial occlusion.
AB  - We report a case of an extraordinarily large tumorous form of ALHE developing on
      the occiput of a 57-year-old Japanese male. Histologically, it was characterized
      by increased numbers of small blood vessels, fibrosis, and lymph follicle
      formations with massive eosinopilia in the dermis in addition to an occluded
      artery in the deep dermis.

PMID- 11837574
TI  - Cutaneous manifestations in childhood staphylococcal sepsis.
AB  - In this article, the clinical and laboratory findings of six (15%) cases of
      cutaneous manifestations of 39 patients with sepsis caused by Staphylococcus
      aureus (S. aureus) were reviewed retrospectively. Our purpose was to determine
      the cutaneous manifestations in patients with sepsis caused by S. aureus. In our
      study, four patients had maculopapular and/or petechial/purpuric rashes, and two
      had erythematous lesions (one of them also had pustular lesions, and the other
      had furuncles). Aside from these, all patients had one or more systemic
      involvement such as bronchopneumonia, arthritis, osteomyelitis, or cardiac
      involvement. In conclusion, our findings suggest that there are no skin findings
      specific to staphylococcal sepsis and that pulmonary infections appear to have a
      high correlation with cutaneous findings, because all of our patients had
      evidence of bronchopneumonia. The mortality of staphylococcal sepsis associated
      with cutaneous findings appears to be high.

PMID- 11837575
TI  - Pseudoxanthoma elasticum: report of a case without any mutations in 5 exons of
      the MRP6 gene.
AB  - Pseudoxanthoma elasticum (PXE) is an inherited systemic disorder of connective
      tissue. We describe a patient with PXE who does not have mutations in exons 16,
      24, 27, 28, and 30 of the MRP6 gene.

PMID- 11837576
TI  - Congenital self-healing reticulohistiocytosis presenting as vesicular eruption.

PMID- 11837577
TI  - Evaluation of image quality and spatial resolution of low-dose high-pitch
      multidetector-row helical high-resolution CT in 11 autopsy lungs and a wire
      phantom.
AB  - PURPOSE: The aim of this study was to evaluate whether low-dose high-pitch (6:1)
      multidetector-row helical high-resolution CT is appropriate for the evaluation of
      various pulmonary abnormalities, including faint opacities. METHODS: Eleven
      autopsy lungs were scanned with a multidetector-row CT scanner using 2.5 mm x 4
      beam collimation, effective slice thickness 3 mm, 6:1 pitch, 0.8 second gantry
      rotation speed, 20 cm Display FOV, high spatial frequency (bone) algorithm, and
      various radiation doses (120 kVp; 160, 80, 40, 24, and 8 mAs). The image quality
      of each CT set was assessed as adequate or inadequate for diagnosis by two
      independent observers. In addition, a wire phantom was scanned with the same
      parameters in order to describe the MTF curves. RESULTS: There was excellent
      agreement between the observers for the evaluation of image quality (kappa
      statistic, 0.84). The ratio of images evaluated as inadequate for 8 mAs and 24
      mAs was significantly higher than that for 160, 80, and 40 mAs (p<0.01: chi
      square test). MTF curves of both 8 and 24 mAs were significantly inferior to
      those of 40, 80, and 160 mAs (p<0.0 1, Friedman test), while the MTF curve of 40
      mAs was relatively inferior to that of 160 mAs (p<0.05, Friedman test).
      CONCLUSION: More than 40 mAs in combination with 120 kVp is preferable for the
      evaluation of details of lung parenchyma by high-pitch. multidetector-row helical
      high-resolution CT.

PMID- 11837578
TI  - Development of a new heating needle for interstitial hyperthermia compatible with
      interstitial radiotherapy.
AB  - PURPOSE: We have developed a new heating needle for interstitial hyperthermia
      compatible with brachytherapy. We studied the heating characteristics of
      interstitial needles and the usefulness of these needles for interstitial
      hyperthermia. MATERIALS AND METHODS: As heating needles, we used MicroSelectron
      HDR interstitial needles. These needles were only heated at the metal tip, and
      were insulated in the middle and grounded from the top. The hyperthermia system
      was based on the principles of RF capacitive heating, and we used a Thermotron RF
      8. We examined whether the temperature and the heating area could be elevated to
      a level required for hyperthermia. RESULT: Good heating was obtained around the
      metal tip of the needle. The heating area of the longitudinal axis of the needle
      varied with the length of the metal part, while the transverse heating area of
      the needle was almost unchanged. If heating was performed while maintaining the
      elevation of temperature in each needle at the same level using variable coils
      (tuning box), heating was homogeneous over the regions in accordance with the
      arrangement of the needles. CONCLUSION: With this heating system, the temperature
      rises easily, and a uniform temperature distribution can be obtained.

PMID- 11837579
TI  - Initial experience of percutaneous renal cryosurgery under the guidance of a
      horizontal open MRI system.
AB  - OBJECTIVE: The aim of this study was to obtain preliminary results of
      cryoablation of renal tumors by using a percutaneous approach guided by a
      horizontal open MRI system, and to assess the safety and efficacy of this
      procedure. MATERIALS AND METHODS: Four patients with renal tumors underwent
      percutaneous cryosurgery with local anesthesia using a horizontal open MRI system
      (AIRIS II, Hitachi Medical Corp., Tokyo, Japan). The size of the mass was
      radiographically documented as 4 cm or less in diameter. A 2- or 3-mm cryoprobe
      was advanced into the renal mass under real-time MR monitoring. Growth of the
      iceball during cryoablation was monitored by two-dimensional MR images. Follow-up
      dynamic CT and physical examination were done after two weeks and six weeks.
      RESULT: MR imaging demonstrated the iceballs as sharply marginated regions of
      signal loss that expanded and engulfed the renal mass with clear contrast between
      the iceball and surrounding tissue. Cryoablated tumors resolved, and there were
      no serious complications and no clinically significant changes during the
      procedures and follow-up study. CONCLUSION: In this limited clinical trial of
      percutaneous renal tumor surgery, cryoablation demonstrated its feasibility with
      minimal morbidity. Intraprocedual MR-guided cryosurgery can be used as a safe
      modality, although further studies are necessary to determine the long-term
      efficacy of this procedure.

PMID- 11837580
TI  - External radiotherapy for decompression of cholangiocellular carcinoma with
      obstructive jaundice: report of a case.
AB  - Percutaneous transhepatic catheter drainage (PTCD) is generally performed for the
      treatment of obstructive jaundice. However, in some cases it is difficult to
      perform insertion because of lack of dilatation of the intrahepatic bile duct. We
      report a patient who had been suffering from jaundice as a result of recurrent
      cholangiocarcinoma near the hilum and whose symptoms were relieved by external
      radiotherapy. We consider radiotherapy for cholangiocarcinoma effective
      palliative treatment for decompression of obstructive jaundice.

PMID- 11837581
TI  - CT-pathologic correlation in a case of solitary plasmacytoma of the rib.
AB  - We report a case of solitary plasmacytoma of rib origin in a 46-year-old man. CT
      revealed a focal expanding mass in the right fifth rib. The mass showed ridging,
      cortical thickening, and fine erosion on the inner aspect of the cortex and had
      partly penetrated the bone. On both T1- and T2-weighted MR images, the mass
      showed low to intermediate intensity, and contrast studies showed homogeneous
      enhancement. Whole body bone scintigraphy revealed abnormal solitary
      accumulation, and therefore surgical resection was performed. Macroscopically the
      specimen revealed destruction of the cortex caused by tumor invasion,
      corresponding to the CT findings. Microscopic findings included a large number of
      plasma cells, leading to a histopathological diagnosis of plasmacytoma.

PMID- 11837582
TI  - Intrathoracic omental herniation through the esophageal hiatus: a case report.
AB  - A case of paraesophageal omental herniation in a 74-year-old man is reported.
      Although computed tomography (CT) and magnetic resonance imaging (MRI) depicted a
      retrocardiac fatty mass that resembled omental herniation, residual concern
      remained regarding lipomatous tumor. Angiography provided decisive evidence of a
      mass containing omental vessels passing through the esophageal hiatus, which led
      to the final diagnosis. The patient underwent a strict course of observation,
      because he had no symptoms or abnormal physical or laboratory findings.
      Paraesophageal omental herniation mimics lipomatous tumors, such as lipoma or
      well-differentiated liposarcoma, extending to both sides of the diaphragm.
      Correct diagnosis of omental herniation requires the evidence of omental fat
      accompanied with omental vessels passing through the esophageal hiatus. Since
      angiography is an invasive diagnostic procedure, we would recommend dynamic MRI
      or reconstructed 3D MR angiography as alternatives to angiography.

PMID- 11837583
TI  - Papillonodular type of cystic partially differentiated nephroblastoma: a case
      report.
AB  - We report a case of the papillonodular type of cystic partially differentiated
      nephroblastoma (CPDN), an extremely rare renal neoplasm that occurs in newborns
      and infants. The papillonodular type of CPDN is a variant of the conventional
      form of CPDN. MRI clearly demonstrated the gross pathologic features,
      distinguishing it from other renal multilocular cystic tumors.

PMID- 11837584
TI  - Experience of two orbital MALT lymphomas treated with radiotherapy, and review of
      the literature.
AB  - Orbital MALT lymphoma is a relatively rare malignant disease, for which radiation
      therapy is effective. However, the optimal dose has not been determined. We
      experienced two cases of orbital MALT lymphoma. One patient was successfully
      treated, but the other developed a severe complication. We conclude that for safe
      treatment of orbital MALT lymphoma, a dose in excess of 40 Gy must not be
      delivered.

PMID- 11837586
TI  - Government sets out proposals for implementing the animal health bill.

PMID- 11837587
TI  - Veterinarian to be struck off for failing to provide adequate care.

PMID- 11837585
TI  - Evaluation of compressed lung CT image quality using quantitative analysis.
AB  - The goals of this study were (1) to evaluate the quality of compressed lung CT
      images obtained using high resolution CT (HRCT: 2 mm slice thickness) for degree
      of compression and conventional CT (10 mm slice thickness) images by using
      physical and subjective evaluations, and (2) to analyze the distortion of density
      distribution on lung CT images using histogram analysis for each compression
      ratio. The coding method was performed according to the Joint Photographic
      Experts Group (JPEG). We physically evaluated the quality of compressed lung CT
      images using the peak signal-to-noise ratio (PSNR) as given by the square root of
      the ratio of the peak value of the gray level squared to the mean square error
      (dB) and subjectively evaluated the CT images using the mean opinion score (MOS).
      The acceptable compression ratio for diagnosis was about 1:6 to 1:7 for
      conventional CT images and about 1:4 to 1:5 for HRCT images as determined by MOS.
      The PSNR corresponding to acceptable compression ratios was about 50 dB. The
      difference in density distribution between HRCT and conventional CT was
      statistically significant (Friedman test: p<0.02) in histogram analysis. Results
      suggested that, in comparison with conventional CT, a high compression ratio was
      not suitable for HRCT.

PMID- 11837588
TI  - Effect of condensed tannins on egg hatching and larval development of
      Trichostrongylus colubriformis in vitro.
AB  - The effects of condensed tannins extracted from seven forages on the viability of
      the eggs and first stage (L1) larvae of the sheep nematode Trichostrongylus
      colubriformis were evaluated in in vitro assays. The extracts of condensed
      tannins were obtained from Lotus pedunculatus (LP), Lotus corniculatus (LC),
      sulla (Hedysarum coronarium), sainfoin (Onobrychus viciifolia), Dorycnium
      pentaphylum (DP), Dorycnium rectum (DR) and dock (Rumex obtusifolius). Extracts
      containing 200 to 500 microg/ml reduced the proportion of eggs that hatched. The
      larval development assay was used to evaluate the effect of the extracts on the
      development of either eggs or L1 larvae to L3 infective larvae. Development was
      allowed to proceed for seven days by which time the larvae in control incubations
      had reached the infective L3 stage. Extracts containing 200 microg/ml from LP,
      DP, DR or dock prevented egg development, and only 11, 8 and 2 per cent of the
      eggs developed to L3 larvae with extracts from LC, sulla and sainfoin,
      respectively. When the concentration was 400 microg/ml no eggs developed to L3
      larvae. The addition of the extracts after hatching also inhibited the
      development of L1 to L3 larvae; 200 microg/ml extracted from LP, LC, sulla,
      sainfoin, DP, DR and dock resulted in only 14, 18, 17, 15, 14, 16 and 4 per cent
      of L1 larvae developing to the L3 stage compared with 85 per cent for controls,
      and 400 microg/ml further reduced the development of L1 larvae. Statistical
      analyses showed that when the extracts were added before hatching they were
      significantly (P<0.001) more effective at inhibiting the larval development than
      when they were added after hatching. The condensed tannins from dock had the
      greatest inhibitory effect on egg development followed by the tannins from DR,
      sainfoin, DP, LP, sulla and LC.

PMID- 11837589
TI  - Postanaesthetic cerebral necrosis in five horses.
AB  - After being anaesthetised for between one hour 40 minutes and seven hours, five
      adult horses developed acute neurological signs and extensive cerebrocortical
      necrosis. Four of them had had abdominal surgery for colic and one had had
      repeated orthopaedic interventions. Between five hours and seven days after the
      surgery, all five horses suddenly developed severe signs of a predominantly
      prosencephalic disturbance: bilateral blindness with normal pupillary light
      responses, abnormal behaviour varying from propulsive pacing to head pressing
      profound lethargy and generalised seizures. They were euthanased between 24 hours
      and three weeks after the onset of these signs. In three of the cases a gross
      examination of the brain revealed patchy malacia of the cerebral grey matter and
      some discolouration of the adjacent white matter. Microscopical examination
      revealed lesions that varied from laminar neuronal necrosis in the grey matter of
      the cerebral cortex to more diffuse necrosis of the cortex and underlying white
      matter. Four of the five cases had had a period of hypercapnea while
      anaesthetised, and two of them (and possibly a third) had also had hypoxaemia.

PMID- 11837590
TI  - Ultrasonographic findings in cows with dilatation, torsion and retroflexion of
      the caecum.
AB  - Thirty cows with caecal dilatation underwent clinical and ultrasonographic
      examinations, followed by a right flank laparotomy and surgical correction. The
      intraoperative findings were compared with the results of the ultrasonographic
      examination. The appearance, position, dimensions, diameter and nature of the
      contents of the caecum and proximal and spiral ansa of the colon were determined
      with a 3.5 MHz linear transducer. The wall of the proximal ansa of the colon and
      of the dilated caecum closest to the abdominal wall was visible in all the cows
      and appeared as an echogenic semicircular line immediately adjacent to the
      peritoneum. The contents of the caecum and of the proximal and spiral ansa of the
      colon were not visible in 21, 25 and 25 cows, respectively, owing to gas. In the
      remaining cows, the contents were hypoechogenic to echogenic in appearance. In
      all of the cows, the dilated caecum was imaged from the right abdominal wall at
      the level of the tuber coxae. The caecum was imaged from the 12th, 11th and 10th
      intercostal spaces in 11, five and three cows, respectively. The caecum and
      proximal ansa of the colon were situated immediately adjacent to the right
      abdominal wall in 28 cows, but in the other two cows parts of these structures
      were pushed away from the abdominal wall by the liver or gall bladder. The
      diameter of the caecum, measured at various sites varied from 7.0 to 25.0 cm.
      Caecal dilatation was diagnosed on the basis of the results of rectal
      examinations in 28 of the cows, but in all 30 cows on the basis of the results of
      the ultrasonographic examinations. Dilatation and caudal displacement of the
      caecum were diagnosed in 18 cows; dilatation and cranioventral retroflexion of
      the caecum were diagnosed in six cows, and dilatation and craniodorsal
      retroflexion of the caecum were diagnosed in two cows. In the four other cows,
      the direction of the retroflexed caecum could not be determined. The diagnosis of
      caecal dilatation based on the ultrasonographic findings was confirmed in all the
      cows during exploratory laparotomy. The results of ultrasonography and
      exploratory surgery with regard to the position of the dilated and sometimes
      retroflexed or twisted caecum were in complete agreement in 18 cases, in partial
      agreement in eight cases, but in four cases did not agree.

PMID- 11837591
TI  - Prevalence of owner-reported respiratory disease in Pony Club horses.

PMID- 11837592
TI  - Incidence, pathology and involvement of Nasitrema species in odontocete
      strandings in the Canary Islands.

PMID- 11837593
TI  - First cases of canine babesiosis in the Slovak Republic.

PMID- 11837594
TI  - Epididymo-orchitis caused by Brucella melitensis in breeding rams in India.

PMID- 11837595
TI  - Porcine dermatitis and nephropathy syndrome in Japan.

PMID- 11837599
TI  - Children with a 22q11 deletion versus children with a speech-language impairment
      and learning disability: behavior during primary school age.
AB  - Children with a 22q11 deletion versus children with a speech-language impairment
      and learning disability: behavior during primary school age: Common behavioral
      features described in children with the Velo-Cardio-Facial syndrome (VCFS) (del
      22q11) are problems with attention and concentration, extremes in behavior and
      social problems, especially in relationship with peers. At present, it is unclear
      whether these behavioral manifestations are directly related to the chromosomal
      anomaly or related to other manifestations of the syndrome such as developmental
      delay and speech-language delay. This study describes for the first time the
      behavior of young primary school aged children with a del22q11 compared to a
      control group of children matched for age, sex and mental level, with similar
      developmental problems (speech-language impairment plus learning disability: SLI
      + LD) but without a del22q11 or any other known genetic condition. Parents and
      teachers evaluated the children's behavior with standardized questionnaires
      (CBCL; TRF). Results indicate that most of the behaviors are similar across both
      groups. The only differences found are in the field of <<withdrawn behavior>> and
      <<aggressive behavior>>. Children with a del22q11 have a stronger tendency to
      withdraw from others, whereas children with a SLI+LD seem to be more aggressive.

PMID- 11837600
TI  - Detection of an unbalanced t(4;15) by FISH in a child with multiple congenital
      anomalies.
AB  - Detection of an unbalanced t(4;15) by FISH in a child with multiple congenital
      anomalies: In this report, we present the clinical history and findings in a 6
      month-old male with multiple congenital anomalies, developmental delay, and an
      initial male karyotype with 4q+. The origin of the additional segment on 4q was
      unequivocally established by fluorescence in situ hybridization (FISH). Whole
      chromosome probe for chromosome 4 and chromosome 15-specific a-satellite probe
      were used. The karyotype was demonstrated to be 46,XY,der(4),
      t(4;15)(q35;?),inv(9)(p13q13). To the best of our knowledge the above cytogenetic
      abnormalities with these clinical findings have not been described previously.
      This case further demonstrates the advantage of FISH in the identification of
      anomalous chromosome regions and breakpoints.

PMID- 11837601
TI  - The 4q-Syndrome.
AB  - The 4q-Syndrome: Here we report four cases of interstitial and terminal deletions
      of the long arm of chromosome 4. Case 1 is a 16 month old boy with del(4)(q12q21)
      who has soft dysmorphic features, tetralogy of Fallot, and severe developmental
      delay. Case 2 is a male infant with the same deletion and congenital
      cardiomyopathy. He suffered severe birth asphyxia and died at the age of 6
      months. His father was found to have a complex chromosome 4 rearrangement. Case 3
      is a female infant with del(4)(q33) who died of aspiration pneumonia. She was
      mildly dysmorphic and presented with heart failure and hypercalcaemia. Case 4 is
      a 8 month old girl who has del(4)(q33) and Pierre-Robin sequence. So far about 70
      patients with microscopically visible deletions of chromosome 4q have been
      described. Although they vary in their phenotypes, they have several features in
      common. We suggest to use the term 4q-syndrome for all macrodeletions of the long
      arm of chromosome 4.

PMID- 11837602
TI  - Report of two cases with Van der Woude syndrome: a child and her mother.
AB  - Report of two cases with Van der Woude syndrome: a child and her mother:
      Congenital pits of the lower lip are rare malformations. They are closely
      associated with cleft lip (CL), cleft lip/palate (CL/CP) or isolated cleft palate
      (CP) and if so this condition is known as Van der Woude syndrome, which is
      inherited in an autosomal dominant fashion with high penetrance. Two individuals,
      one with lower lip pits and cleft palate and the other with isolated lower lip
      pit from the same family are described. Autosomal dominant pattern of inheritance
      was observed in this family and treatment consisted of complete removal of sinus
      tracts in one patient. Pathological features of sinus tracts consisted of
      stratified nonkeratinized squamous epithelium and a lamina propria of dense
      connective tissue. Importance of genetic counseling is emphasized as at least
      half of gene carriers have some kind of clefting.

PMID- 11837603
TI  - Hypoglossia-hypodactyly syndrome: report of 2 patients.
AB  - Hypoglossia-hypodactyly syndrome: report of 2 patients: Two newborns with severe
      limb deformities and hypoglossia, with micro- and retrognathia are reported. The
      first patient had a transverse agenesia just below the knee of both legs and
      below the elbow of both arms. A Krukenberg phalangisation was performed and
      rehabilitation of march with prosthetics at an early age. The second child had
      less severe deformities and needed no corrective surgery till now.

PMID- 11837604
TI  - Intrafamilial clinical variability in type C brachydactyly.
AB  - Intrafamilial clinical variability in type C brachydactyly: In this report we
      describe a 4-generation family in which three members present variable clinical
      and radiological manifestations of brachydactyly type C. The observation of
      'skipped generations' in the present family and in a few other families reported
      previously, may indicate that brachydactyly type C is not a true autosomal
      dominant condition due to mutations in a single gene.

PMID- 11837605
TI  - In search of a 9q13 latent centromere in 9qh polymorphic inversions.
AB  - In search of a 9q13 latent centromere in 9qh polymorphic inversions: The presence
      of alphoid sequences in 9q13 has prompted the suggestion that such a region could
      harbor a latent centromere which under certain circumstances may appear as a
      neocentromere. We tested this hypothesis by means of FISH with a centromere 9
      specific alphoid probe in lymphocyte metaphases from 13 unrelated individuals
      with a 9qh polymorphic inversion. Since all inverted chromosomes had the alphoid
      signal onto the primary constriction, it was not possible to identify any
      neocentromere . We believe, however, that the number of cases was not enough to
      conclude that all the polymorphic inversions of chromosome 9 are genuine.

PMID- 11837606
TI  - Interchange trisomy 21 by t(1;21)(p22;q22)mat.
AB  - Interchange trisomy 21 by t(1:21)(p22:q22)mat: Interchange trisomy 21 by
      t(1;21)(p22;q22)mat was identified in a sporadic patient with Down syndrome. With
      a 21q22 specific probe, we observed signals on both normal 21 chromosomes and on
      the der. We reviewed the 23 published reports of families with reciprocal
      translocations leading to viable offspring with interchange trisomy 21. The
      breakpoints in chromosome 21 were mainly located in 21q (19/24 instances,
      including the present report) and in 19/23 cases the other chromosome involved in
      the translocation was <<large>> (pairs 1-12). The underlying 3:1 segregation
      occurred mainly in carrier mothers; only one patient presented a de novo
      imbalance and in another case the father was the carrier. In addition, there were
      4 instances of concurrence with another unbalanced segregation (adjacent-1 or
      tertiary trisomy) and 3 families with recurrence of interchange trisomy 21. The
      mean age of 14 female carriers at birth of interchange trisomy 21 offspring (24.8
      yr) was lower that the mean (28.3 yr) found in a larger sample of mothers of
      unbalanced offspring due to 3:1 segregation (mostly tertiary trisomics) and was
      not increased with respect to the general population average. Overall, these data
      agree with previous estimates regarding recurrence risk (9-15%) and abortion rate
      (about 28%) in female carriers ascertained through an interchange trisomic 21
      child.

PMID- 11837607
TI  - Larsen syndrome associated with severe congenital hydrocephalus.
AB  - Larsen syndrome associated with severe congenital hydrocephalus: Larsen syndrome
      (LS) is characterized by the association of flattened facies with a prominent
      forehead, a depressed nasal bridge and hypertelorism, dislocation of hips, elbows
      and knees, equinovarus or valgus deformities of the feet, long and tapering
      fingers, normal intelligence. Hydrocephalus has rarely been reported in
      association with LS. In this article, a newborn infant with the classical
      features of LS and severe congenital hydrocephalus is presented. Our purpose was
      to emphasize the importance of congenital hydrocephalus in infants with LS and to
      highlight the management of cases of LS associated with congenital hydrocephalus.

PMID- 11837608
TI  - An analysis of seven infants with Brachmann-de Lange syndrome, of whom two
      identical twin sisters.
AB  - An analysis of seven infants with Brachmann-de Lange syndrome, of whom two
      identical twin sisters: Brachmann-de Lange syndrome (BDLS) is characterized by
      typical facial features, intrauterine growth retardation, short stature,
      microbrachycephaly, hirsutism and limb anomalies. Here, we reviewed the findings
      of seven infants with BDLS, of whom two were identical twin sisters of normal
      parents. All of the infants' parents were normal, and no consanguinity between
      the parents was noted although the ratio of consanguineous marriages is very high
      (21.1%) in Turkey. It is well known that most cases of BDLS are sporadic, some
      cases of this disorder are inherited in an autosomal dominant trait. Our findings
      suggested that familial cases of BDLS were infrequent, and vast majority of cases
      appeared to be sporadic and the occurrence of the syndrome in the identical twin
      sisters of normal parents was also thought a heterogeneity in this condition,
      overlapping with other conditions and syndromes as mentioned by Fryns et al.

PMID- 11837609
TI  - The ICF syndrome: new case and update.
AB  - The ICF syndrome: New case and update: We report the clinical progress in a 5
      year-old boy with the <<Immunodeficiency-Centromere Instability-Facial
      anomalies>> (ICF) syndrome. Early diagnosis and intervention has led to a good
      outcome. DNMT3B mutation analysis was negative, supporting genetic heterogeneity
      in this condition.

PMID- 11837610
TI  - Choroid plexus cysts and oligohydramnios: presenting echographic signs in a
      female fetus with deletion of the Wolf-Hirschhorn syndrome region (4p16.3).

PMID- 11837611
TI  - Quantitative reflection spectroscopy at the human ocular fundus.
AB  - A new model of the reflection of the human ocular fundus on the basis of the
      adding-doubling method, an approximate solution of the radiative transport
      equation, is described. This model enables the calculation of the concentrations
      of xanthophyll in the retina, of melanin in the retinal pigment epithelium and
      the choroid, and of haemoglobin in the choroid from fundus reflection spectra.
      The concentration values found in 12 healthy subjects are in excellent agreement
      with published data. In individual cases of pathologic fundus alterations,
      possible benefits to the ophthalmologic diagnostics are demonstrated.

PMID- 11837612
TI  - Haemoglobin oxygenation of a two-layer tissue-simulating phantom from time
      resolved reflectance: effect of top layer thickness.
AB  - A dual wavelength time-resolved reflectance system was developed for monitoring
      haemoglobin saturation noninvasively. At each wavelength, the time-resolved
      reflectance data were fitted to a diffusion model of light propagation in a
      homogeneous, semi-infinite medium to yield the absolute scattering and absorption
      coefficients. The absorption coefficients were then used to calculate haemoglobin
      saturation. A two-layer phantom containing human erythrocytes in a scattering
      solution in the bottom layer was used to study system performance under more
      realistic conditions. The top layer was chosen to simulate either skin or fat and
      the oxygenation of the bottom layer, which corresponded to muscle, was
      controlled. The thickness of the fat layer was varied from 1.5 to 10 mm to
      investigate the effects of increasing the top layer thickness. These results,
      obtained with the simple diffusion model, were compared with simultaneous
      measurements of oxygenation made directly in the bottom layer. Errors in
      estimating haemoglobin saturation with this method ranged from 5-11% depending on
      the thickness of the top layer and its optical properties.

PMID- 11837613
TI  - A mathematical model of post-canalization thrombolysis.
AB  - During the initial phase of lysis of an occlusive thrombus using lytic agents
      such as tissue plasminogen activator, blood flow through the centre of the clot
      is established (the process of recanalization). Following canalization, the clot
      remains on the vessel wall and further lysis is required. This paper develops a
      multi-species mathematical model to describe the bulk chemical reactions in the
      bloodstream and the convective and diffusive transport of chemical species to and
      from the clot surface in conditions following canalization. For the steady state
      case, the model indicates that the process of clot lysis following initial
      recanalization is dominated by surface chemical reactions and the bulk reactions
      play little role in the lytic process. Lytic rate is dependent on the clot
      geometry and flow conditions. The rate of clot dissolution is greatest at the
      upstream end of the clot and decreases steadily downstream due to lytic agent
      being removed from the flowing blood as it binds to the clot surface. This model
      may be further developed and used to simulate and compare different lytic
      regimes.

PMID- 11837614
TI  - A method to quantify the dynamics and complexity of re-entry in computational
      models of ventricular fibrillation.
AB  - Ventricular fibrillation is a deadly cardiac arrhythmia. There is evidence that
      electrical activity in cardiac tissue is sustained during fibrillation by re
      entrant waves that rotate around filaments. In this paper we develop a method for
      identifying and tracking filaments in a computational model of ventricular
      fibrillation. This method identifies the birth, death, bifurcation and
      amalgamation of filaments and these events are summarized on a directed graph.
      The approach described in this study provides ways to quantify the complex
      patterns of electrical activity seen in computational models of fibrillation, to
      relate the behaviour of computational models to experimental data and thus to
      gain insights into the underlying mechanisms of this dangerous arrhythmia.

PMID- 11837615
TI  - Dosimetry characteristics of degraded electron beams investigated by Monte Carlo
      calculations in a setup for intraoperative radiation therapy.
AB  - Degraded electron beams, as used for intraoperative radiation therapy (IORT) or
      similar complicated dosimetric situations, have different characteristics
      compared to conventional electron therapy beams. If international dosimetry
      protocols are applied in a direct manner to such degraded beams, uncertainties
      will be introduced in the absorbed dose determination. The Monte Carlo method has
      been used to verify experimentally determined relative absorbed dose
      distributions and output factors in an IORT geometry. Monte Carlo generated dose
      distributions are mostly within +/-2% or +/-2 mm of measured data. The simulated
      output variation between the IORT cones (relative output factors) are mostly
      within 2% of measured values. By comparing IORT and conventional electron beam
      characteristics (e.g. energy spectra, angular distributions and the contributions
      of different system components to these quantities) limitations and uncertainties
      of commonly used dosimetric techniques in IORT electron fields are quantified.
      The intraoperative treatment field contains a larger amount of scattered
      electrons, which leads to a broader energy spectrum as well as a wider angular
      distribution of electrons at the phantom surface. The dose from the scattered
      electrons can contribute up to 40% of the total dose at a depth of dose maximum,
      compared to approximately 10% for standard beams. A study of the energy spectra
      at the reference depth reveals that an uncertainty of the order of 1% can be
      introduced if ionization chamber based dosimetry is used to determine output
      factors for the investigated IORT system. We recommend that relative absorbed
      dose distributions and output factors in IORT electron beams and for similar
      complicated dosimetric situations should be determined with detectors having a
      small energy and angular dependence (e.g. diamond detectors or p-Si diodes).

PMID- 11837616
TI  - Intensity-modulated radiation therapy using only jaws and a mask.
AB  - Intensity-modulated radiation therapy (IMRT) generally requires complex equipment
      for delivery. Just one study has investigated the use of 'jaws-only' IMRT with
      not discouraging conclusions. However, the monitor-unit efficiency is still
      considered to be too low compared with the use of a multileaf collimator (MLC).
      In this paper a new IMRT delivery technique is proposed which does not require
      the MLC and is only moderately more complex than the use of jaws alone. In this
      method a secondary collimator (mask) is employed together with the jaws. This
      mask may translate parallel to the jaw axes. Two types of mask have been
      investigated. One is a regular binary-attenuation pattern and the other is a
      random binary-attenuation pattern. Studies show that the monitor-unit efficiency
      of this 'jaws-plus-mask' technique, with a random binary mask, is more than
      double that of the jaws-only technique for typical two-dimensional intensity
      modulated beams of size 10 x 10 bixels2 and with a peak value of 10 MU (or
      quantized into 10 fluence increments). For two-dimensional intensity-modulated
      beams of size 15 x 15 bixels2 with a peak value of 10 MU (or quantized into 10
      fluence increments), the monitor-unit efficiency of the 'jaws-plus-mask'
      technique with a random binary mask is almost triple that of the jaws-only
      technique. Some further extensions to this concept are presented showing that
      some more practical mask arrangements are possible but with somewhat compromised
      monitor-unit efficiency. Some comments are provided on practicalities and on
      delivery times.

PMID- 11837617
TI  - Generating compensation designs for tangential breast irradiation with artificial
      neural networks.
AB  - In this paper we discuss a study comparing an algorithm implemented clinically to
      design intensity-modulated fields with two artificial neural networks (ANNs)
      trained to design the same fields. The purpose of the algorithm is to produce
      compensation for tangential breast radiotherapy in order to improve dose
      homogeneity. This was achieved by creating intensity-modulated fields to
      supplement standard wedged fields. Portal image data were used to create
      thickness maps of the medial and lateral fields, which in turn were used to
      design the wedged and intensity-modulated fields. The ANNs were developed to
      design the intensity-modulated fields from the portal image data and
      corresponding fluence map alone. One used localized groups of portal image pixels
      related to the fluence map (method 2), and the other used a one-to-one mapping
      between spatially corresponding pixels (method 3). A dosimetric comparison of the
      methods was performed by calculating the overall dose distribution. The volume of
      tissue outside the dose range 95-105% was used to assess dose homogeneity. The
      average volume outside 95-105%, averaged over 80 cases, was shown to be 2.3% for
      the algorithm, whilst average values of 9.9% and 13.5% were obtained for methods
      2 and 3, respectively. The results of this study demonstrate the ability of an
      ANN to learn the general shape of compensation required and explore the use of
      image-based ANNs in the design of intensity-modulated fields.

PMID- 11837618
TI  - Influence of the angle of incidence on the sensitivity of gamma camera based PET.
AB  - Thicker crystals have been used to increase the detection efficiency of gamma
      cameras for coincidence imaging. This results in a higher detection probability
      for oblique incidences than for perpendicular incidences. As the point
      sensitivity at different radial distances is composed of coincidences with
      different oblique incidences, the thickness of the crystal will have an effect on
      the sensitivity profiles. To correct this non-uniform sensitivity, a sensitivity
      map is needed which can be measured or calculated. For dual- or triple-head gamma
      camera based positron emission tomography (PET) a calculated sensitivity map is
      preferable because the radius and the head orientation often change between
      different acquisitions. First, these sensitivity maps are calculated for 2D
      acquisitions by assuming a linear relationship between the detection efficiency
      and the crystal thickness. The 2D approximation is reasonable for gamma cameras
      with a small axial acceptance angle. The results of the 2D approximation show a
      good agreement with the results of Monte Carlo simulations of different realistic
      gamma camera configurations. For dual-head gamma cameras the influence on the
      sensitivity profile is limited. Greater variation of the sensitivity profile is
      seen on three-headed gamma cameras and correction of this effect is necessary to
      obtain uniform reconstruction. To increase the sensitivity of gamma cameras,
      axial collimators with larger acceptance angles are used. To obtain a correct
      sensitivity for these cameras a sensitivity calculation in 3D is needed. For a
      fixed camera position the sensitivity is obtained by integrating the detection
      efficiency over the solid angle formed by the voxel and the intersection of the
      first detector with the projection of the second detector on the plane of the
      first detector. The geometric sensitivity is obtained by averaging this for all
      camera angles. The values obtained show a good agreement with the Monte Carlo
      simulations for different points in the field of view. Both 2D and 3D sensitivity
      profiles show the highest influence of the detector thickness on the radial
      profiles of the U-shape configuration. Taking the detector thickness into account
      also has an influence on the axial profiles. This influence is maximal in the
      centre where more oblique coincidences are present. This method is not limited to
      gamma camera based PET scanners but can be used to calculate the sensitivity of
      any PET camera with continuous detector blocks.

PMID- 11837619
TI  - Dual-energy tissue cancellation in mammography with quasi-monochromatic x-rays.
AB  - Dual-energy radiography has not evolved into a routine clinical examination yet
      due to intrinsic limitations of both dual-kVp imaging and single-exposure imaging
      with conventional x-ray sources. The recent introduction of novel quasi
      monochromatic x-ray sources and detectors could lead to interesting improvements,
      especially in mammography where the complex structure of healthy tissues often
      masks the detectability of lesions. A dual-energy radiography technique based on
      a tissue cancellation algorithm has been developed for mammography, with the aim
      of maximizing the low intrinsic contrast of pathologic tissues while being able
      to minimize or cancel the contrast between glandular and fat tissues. Several
      images of a plastic test object containing various tissue equivalent inserts were
      acquired in the energy range 17-36 keV using a quasi-monochromatic x-ray source
      and a scintillator-coated CCD detector. Images acquired at high and low energies
      were nonlinearly combined to generate two energy-independent basis images.
      Suitable linear combinations of these two basis images result in the elimination
      of the contrast of a given material with respect to another. This makes it
      possible to selectively cancel certain details in the processed image.

PMID- 11837620
TI  - Broadband ultrasound attenuation imaging: algorithm development and clinical
      assessment of a region growing technique.
AB  - This paper presents a computerized method for the selection of an irregular
      region of interest (ROI) in broadband ultrasound attenuation (BUA) images. A
      region growing algorithm searches an initial region in the posterior part of the
      calcaneus until the pixel with the lowest attenuation value is found; this is the
      starting seed. Then, the algorithm evaluates the values of the eight pixels
      neighbouring the starting seed. Pixels that have the closest value to the
      starting seed are accepted. This procedure is the first processing level. The
      procedure is repeated for the group of pixels neighbouring those accepted from
      the previous processing level. The algorithm ceases when the number of accepted
      pixels reaches a user-specified number. The clinical part of this study compares
      measurements of BUA at an automatic ROI implemented on a quantitative ultrasound
      imaging device, defined as the circular region of lowest attenuation in the
      posterior part of the calcaneus, and at irregular ROIs of various sizes generated
      by the algorithm developed in this study. The algorithm was applied to BUA images
      obtained from 24 post-menopausal women with hip fractures and 26 age-matched
      healthy female subjects. The use of the irregular ROI with a size of 2400 pixels
      is proposed because that region yielded better clinical results compared to
      irregular ROIs with different size and the circular automatic ROI.

PMID- 11837621
TI  - A new method for preventing pulse pileup in scintillation detectors.
AB  - A new method for preventing pulse pileup in scintillation detectors is proposed.
      In the new method (G-INT), the energy of an event is calculated from the 'gated
      integral' of the pulse signal and the period of integration. The period of
      integration is not fixed but is shortened by the arrival of the succeeding pulse
      so as to avoid post-pulse pileup. The effect of pre-pulse pileup is corrected by
      subtracting the remnant energy of the preceding pulses, which is calculated from
      the gated integral of the preceding pulse. To avoid error due to short pulse
      intervals, pre- and post-pulse deadtimes are imposed. The method is similar to
      Wong's method (W-SUM) that depicts the energy by the 'weighted sum' of the
      current signal and the integrated signal. The performance of G-INT has been
      studied by Monte Carlo simulation in comparison with W-SUM, the variable sampling
      time technique and simple delay-line clipping. It is shown that G-INT provides
      the smallest degradation in pulse height resolution for a given count rate
      capability. The difference between G-INT and W-SUM is explained by the difference
      in the amount of statistical noise involved in the gated integral and in the
      weighted sum.

PMID- 11837622
TI  - Dielectric behaviour of gap junction connected cells: a microscopic approach.
AB  - The dielectric behaviour of interconnected cells is simulated by taking into
      account the 'real' shape. In previous work, we derived the polarizability of non
      spherical, shelled, particles by solving the related integral equation using a
      spectral decomposition. The permittivity and impedance modulus spectra of gap
      junction connected cells are compared with those provided by a suspension of
      ellipsoids (prolate spheroids) having the same shape as the individual cells
      connected through gap junction, and the same volume fraction. This approach aims
      to provide a microscopic hint on the effect of the closing of gap junctions
      reported on the dielectric behaviour of ischaemic tissues, as well as to offer a
      rough approximation of a tissue by considering high concentrations of oriented
      gap junction connected cells.

PMID- 11837623
TI  - The role of gatekeeping as a tool in healthcare delivery.

PMID- 11837624
TI  - Pre-emptive renal transplantation: the way forward.

PMID- 11837625
TI  - Management of snoring.

PMID- 11837627
TI  - Morbidity data collection in general practice: experience in the South Eastern
      Health Board 1998-1999.
AB  - A joint project between general practitioners and the South Eastern Health Board
      resulted in the establishment of a network of computerised practices collecting
      morbidity data in 1998 - 1999. Five practices established age sex registers for
      public and private patients. The International Classification of Primary Care 2
      (ICPC-2) was used to define inclusion criteria for a range of illnesses relevant
      to primary care and public health. Problems arose in validating and extracting
      data in three practices. Disease prevalence for 17 illnesses was established for
      two practices only. The project clearly established the problems associated with
      morbidity data collection in general practice which include absence of a national
      patient registration system, absence of a national electronic messaging standard,
      difficulties extracting data from practice software systems and the need for a
      high level of dedicated staff and resources to implement such a project.

PMID- 11837626
TI  - Maxillary artery embolisation in the management of epistaxis.
AB  - Serious consideration needs to be given to the importance of early embolisation
      of the maxillary artery in severe and refractory epistaxis. This is particularly
      true in the young fit person with traumatic epistaxis and in the elderly person
      who is unfit for general anaesthesia. Embolisation is now a safe and reliable
      technique. Six patients were embolised. In the two institutions from 1999 - 2000.
      All responded well to embolisation without complication. This paper describes the
      technique used in our hospitals and suggests that with the advent of platinum
      coils and pre embolisation arteriography, the chances of cerebrovascular accident
      is very small.

PMID- 11837628
TI  - Trends in periconceptional folic acid use by relatives in Irish families with
      neural tube defects.
AB  - Close relatives in families who have a child with a neural tube defect (NTD) are
      at greatly increased risk of having an affected child. Periconceptional folic
      acid reduces the risk of both occurrence and recurrence of NTDs substantially.
      Public health authorities currently recommend that the diets of all women between
      the ages of 15 and 44 who are capable of becoming pregnant be supplemented with
      folic acid tablets daily. We wondered if relatives in NTD families were more
      likely to use folic acid. From data obtained by interview with uncles and aunts
      in Irish NTD families we evaluated folic acid use in 144 of their pregnancies
      occurring between 1990 and 2000. There was a significant trend towards increasing
      use of folic acid both before and during pregnancy over the 10 years covered by
      the study. During the most recent years, 1998-2000, 57.9% of pregnancies reported
      by aunts were supplemented beforehand and 89.5% during the pregnancy. Pregnancies
      to smokers were significantly less likely to be supplemented with folic acid. In
      this study close relatives of an NTD child were more likely to report
      periconceptional folic acid use than the general public. While these results are
      encouraging, more remains to be done to ensure in this high risk group to ensure
      that the full prevention potential of folic acid is realised.

PMID- 11837630
TI  - The problem of seeing hospital staff without G.P. referral--the otolaryngological
      experience.
AB  - Over a three month period, a record was kept of the number of hospital staff who
      approached the E.N.T. team requesting help for a medical problem. Staff members
      included doctors, nurses, clerical staff, paramedical staff and porters. The
      total number of employees in the hospital was recorded. The average General
      practitioner public patient list (General medical Service cardholders) for South
      Dublin was recorded (our hospital is in south west Dublin). The total number of
      hospital staff seen by E.N.T. in 3 months was seventy seven. The total number of
      hospital staff seen by other surgical specialties was approximately one hundred
      and sixty seven. Extrapolation of numbers seen by E.N.T. service in three months
      to numbers seen over a one year period is 308 patients. The numbers seen by the
      E.N.T. service in three months corresponds to 11.7% of the average South Dublin
      General Practitioner Medical card list. It has been estimated that approximately
      20% of all problems the average General practitioner sees in a week are E.N.T.
      related. Those practices with a smaller paediatric population would have
      approximately 15% of the total practice concearned with E.N.T. problems.
      Therefore as 15% of 2,400 (total hospital staff) = 360, there is potentially a
      small General Practice which is 'hidden' within the hospital.

PMID- 11837629
TI  - Association of Fallot Tetralogy with Carney's complex.
AB  - The Carney complex is an inherited, autosomal disease of multicentric tumors in
      many organs. Some components of Carney's complex are cardiac myxoma, spotty
      pigmentation, and endocrine overactivity. Primary pigmented nodular
      adrenocortical dysplasia (PPNAD) is an exceedingly rare cause of Cushing's
      syndrome in infants, children, and young adults. PPNAD occurs sporadically or as
      part of a familial syndrome called Carney's complex. Up to our knowledge, the
      association of Fallot Tetralogy with Carney's complex has not been previously
      reported. We presented, a 20-year-old woman, who had been operated for Fallot
      Tetralogy at the age of 3 years, had Carney's complex, i.e. left atrial myxoma,
      two facial spotty pigmented areas, and PPNAD.

PMID- 11837631
TI  - Gastric antral vascular ectasia--a cause of refractory anaemia in systemic
      sclerosis.
AB  - Recurrent gastrointestinal haemorrhage is an uncommon manifestation of systemic
      sclerosis. We report a case of gastrointestinal bleeding due to gastric antral
      vascular ectasia (GAVE) in a patient with systemic sclerosis. Failure to
      recognise the condition as a cause of gastrointestinal bleeding may delay the
      instigation of appropriate treatment. GAVE should be considered in the
      differential diagnosis of anaemia in patients with autoimmune conditions such as
      systemic sclerosis and primary biliary cirrhosis.

PMID- 11837632
TI  - An unusual cause for tinnitus.
AB  - Central giant cell granulomas of the skull base are uncommon entities. They
      usually present at the epiphyses of long bones such as the proximal femur and
      distal radius. Otological symptoms are not known as a common presenting symptom
      of giant cell granulomas.

PMID- 11837633
TI  - Direct inguinal hernia strangulating through the superficial inguinal ring.

PMID- 11837634
TI  - Effect of gastroenteritis during pregnancy on neonatal outcome.
AB  - Previous studies have shown that gastrointestinal disease in women during
      pregnancy may be a risk factor for low-birthweight infants. In the present study,
      the prevalence of gastroenteritis during pregnancy and its effect on neonatal
      outcome was examined for each gestational month in 10,597 single-birth mother
      infant pairs in the ABIS Project (All Babies in Southeast Sweden). After
      exclusion of mothers with inflammatory bowel disease, celiac disease, lactose
      intolerance, or cow's milk allergy, data on the remaining 10,229 mother-infant
      pairs were compiled. Overall, 32.5% of the mothers suffered from gastroenteritis
      during pregnancy (95% confidence interval [CI], 32.5-32.5%). Risk factors
      included young maternal age (P for trend, <0.001), previous infants (P<0.001),
      work in a pediatric day-care facility (P=0.004), and experience of a major life
      event (P=0.027). Binary logistic and multiple linear regression analyses were
      adopted for the following variables of neonatal outcome: birth week, preterm
      birth (<37 weeks), birthweight, low birthweight (< or = 2,499 g), birth length,
      cesarean section, and hospitalization in a neonatal care unit. Maternal
      gastroenteritis during month 4 (-0.18 week; 95%CI=-0.36, -0.01 week), month 5 (
      0.30 week; 95%CI=-0.49, -0.11 week), or month 7 (-0. 18 week; 95%CI=-0.35, -0.01
      week) of pregnancy was associated with a shorter pregnancy (adjusted for
      confounders). Gastroenteritis during part of the pregnancy was associated with a
      shortened pregnancy, but it had no other adverse effects on neonatal outcome. The
      reduction in the duration of pregnancy is probably of little clinical relevance.
      These findings should be confirmed in a prospective study.

PMID- 11837635
TI  - Stability of antibodies to Bordetella antigens in German adults.
AB  - To estimate the rate of asymptomatic exposure to Bordetella pertussis antigens in
      the German adult population and to evaluate the stability of antibodies to these
      antigens, antibody levels against Bordetella antigens and their variability over
      time were measured in German adult blood donors. One hundred forty-six regular
      blood donors (41 females, 105 males) were tested repeatedly for antibodies of
      isotypes IgG and IgA to pertussis toxin, filamentous hemagglutinin (FHA) and
      pertactin over a period of 2-5 years. Overall, 86% and 56% had IgG or IgA
      antibodies to pertussis toxin, respectively, 100% and 92% had IgG or IgA
      antibodies to FHA, respectively, and 83% and 93% had IgG or IgA antibodies to
      pertactin, respectively. One significant titer increase of both IgG anti-FHA and
      IgG anti-pertactin, one of IgG anti-FHA, and two of IgA anti-FHA as well as one
      significant decrease of IgG anti-pertussis toxin were observed during an
      observation period of 480.5 person-years. Antibody concentrations in men and
      women were not different. The data show that the level of antibodies to pertussis
      toxin, FHA, and pertactin remains stable over several years. Furthermore,
      depending on the definition of serological evidence, the rate of significant
      increases or decreases suggesting unrecognized exposure to Bordetella antigens
      was estimated to be between <0.2 and 1.0 per 100 person-years in the population
      studied.

PMID- 11837636
TI  - Antimicrobial susceptibility of respiratory isolates of Enterobacteriaceae and
      Staphylococcus aureus in Italy: incidence and trends over the period 1997-1999.
AB  - The antibiotic susceptibility of members of the family Enterobacteriaceae and of
      Staphylococcus aureus strains isolated from the respiratory tract was assessed
      over the period 1997-1999 as part of the Italian Epidemiological Observatory
      survey sponsored by the Smith-Kline Foundation. A standardised method was used to
      determine the MICs of 22 antibiotics against isolates of Klebsiella pneumoniae
      (n=870), Escherichia coli (n=684), Enterobacter cloacae (n=342), Enterobacter
      aerogenes (n=187) and Serratia marcescens (n=135) as well as the MICs of 11
      antibiotics against isolates of Staphylococcus aureus (n=1,606). Overall, the
      susceptibility rate of Enterobacteriaceae isolates was > or = 90% to 5 agents
      (meropenem, imipenem, amikacin, cefepime and gentamicin); 89-80% to 2 agents
      (ciprofloxacin and tobramycin); and <80% to 11 agents (cefotaxime, piperacillin
      tazobactam, trimethoprim-sulfamethoxazole, cefetamet, ceftriaxone, ceftazidime,
      aztreonam, ticarcillin-clavulanate, tetracycline, piperacillin, cefuroxime,
      chloramphenicol, ticarcillin, amoxicillin-clavulanate and amoxicillin). During
      the 3-year monitoring period, antibiotic susceptibility increased in Klebsiella
      pneumoniae against amoxicillin-clavulanate, in Escherichia coli against third
      generation cephalosporins and aztreonam, in Enterobacter aerogenes against
      amoxicillin and piperacillin-tazobactam and in Serratia marcescens against most
      of the antibiotics. In contrast, Enterobacter cloacae showed a tendency to
      develop resistance to cefetamet, amikacin and ciprofloxacin. Of the total number
      of Staphylococcus aureus strains, 38% were methicillin resistant. Nearly 80% of
      the methicillin-resistant strains displayed a multiresistance pattern (additional
      resistance to 2 or more non-beta-lactam antibiotics). Rates of susceptibility of
      particular species (Klebsiella pneumoniae, Escherichia coli, Staphylococcus
      aureus) were compared using strains from different geographical areas of Italy
      (northern, central and southern) and from different nosocomial areas
      (outpatients, intensive care unit [ICU] inpatients, non-ICU inpatients).
      Susceptibility of Klebsiella pneumoniae to several antibiotics was lower in
      southern Italy, whereas the incidence of methicillin-resistant strains was higher
      in northern and central Italy. The susceptibility of Escherichia coli was similar
      in all three areas. No significant differences in susceptibility of Klebsiella
      pneumoniae or Escherichia coli were found between strains from inpatients and
      outpatients or from inpatients admitted to ICU and non-ICU units. The incidence
      of methicillin-resistant Staphylococcus aureus was higher in ICU inpatients (52%)
      than in non-ICU inpatients (38%) and lower in outpatients (19%) than in
      inpatients.

PMID- 11837637
TI  - Contribution of serological tests and blood culture to the early diagnosis of
      systemic candidiasis.
AB  - The isolation of Candida species from a single blood culture is considered
      sufficient evidence for the initiation of systemic antifungal therapy. However,
      blood cultures still lack sensitivity. Previous reports have suggested that the
      combined serological detection of mannanemia and anti-mannan antibodies may be
      useful for the diagnosis of systemic candidiasis caused by Candida albicans
      (specificity and sensitivity 93% and 80%, respectively). In this study,
      serological tests to detect Candida albicans mannan and Candida albicans
      antibodies (Platelia Candida Antigen and Antibody tests; Bio-Rad, France) were
      applied retrospectively to a series of patients with at least one Candida
      positive blood culture and from whom at least one serum sample, taken before or
      on the day of blood culture, was available. Forty-five patients were selected,
      including 23 infected by Candida albicans, 4 by Candida glabrata, 9 by Candida
      tropicalis, 5 by Candida parapsilosis, and 4 by Candida krusei. Serological tests
      were positive in 73% of patients at least 2 days, and in some patients, up to 15
      days before blood cultures became positive. These data suggest that serological
      surveillance of at-risk patients using the Platelia Candida tests could result in
      earlier initiation of antifungal therapy, especially when used in conjunction
      with blood cultures. In this way, more efficient management of nosocomial
      infections caused by Candida species can be achieved.

PMID- 11837638
TI  - Limited immune reconstitution at intermediate stages of HIV-1 infection during
      one year of highly active antiretroviral therapy in antiretroviral-naive versus
      non-naive adults.
AB  - Although several reports have attributed the clinical benefits of highly active
      antiretroviral therapy (HAART) to a possible immune restoration, long-term data
      are still scarce and most derive from patients with either advanced or very early
      stages of HIV infection. In the present study, changes in lymphocyte subsets,
      activation markers, and adhesion molecules in CD4+ and CD8+ lymphocytes were
      carefully monitored over a 1-year period in 27 HIV-infected adults at an
      intermediate stage of HIV infection. Cytokine-producing patterns were also
      studied. In these patients the HIV viral load disappeared by month 4 of HAART.
      Only limited immunological changes were observed: an incomplete recovery of naive
      CD4+ T cells, a less activated state of CD8+ T cells, and a repopulation of IL-2-
      and IFN-gamma-producing CD4+ T cells. These changes were observed principally in
      patients with more advanced disease. Furthermore, HIV-infected subjects who had
      received HAART previously showed less marked immunological changes than
      antiretroviral-naive individuals. In conclusion, the sustained viral suppression
      during 1 year of HAART was accompanied by limited immunological recovery at
      intermediate stages of HIV infection. This finding indicates a need for longer
      HIV suppression in order to achieve effective recovery of the immune system.

PMID- 11837639
TI  - Nocardia farcinica infection of a cochlear implant in an immunocompetent boy.
AB  - The first case of an infection caused by Nocardia farcinica on a cochlear implant
      and its progression is described. As it is difficult to diagnose Nocardia spp.,
      the identification was confirmed by phylogenetic analysis using 16S rDNA
      sequencing.

PMID- 11837640
TI  - Determining the frequency of resistance of Streptococcus pneumoniae to
      ciprofloxacin, levofloxacin, trovafloxacin, grepafloxacin, and gemifloxacin.
AB  - Newer fluoroquinolones have good activity against Streptococcus pneunoniae and
      may be useful clinically for the treatment of pneumonia. Although resistance
      among Streptococcus pneumoniae has been reported, it is rare. The frequency of
      single-step resistance and the emergence of resistance were compared in serial
      transfer of 49 clinical isolates of penicillin-sensitive and -resistant
      Streptococcus pneumoniae to ciprofloxacin, levofloxacin, trovafloxacin,
      grepafloxacin, and gemifloxacin. Single-step resistance frequencies to four times
      the minimum inhibitory concentration were 2.73 x 10(-6) (+/- 8.46 x 10(-6)) for
      ciprofloxacin, 1.78 x 10(-7) (+/- 4.62 x 10(-7)) for trovafloxacin, 5.45 x 10(-7)
      (+/- 1.24 x 10(-6)) for grepafloxacin, 6.78 x 10(-7) (+/- 1.38 x 10(-6)) for
      gemifloxacin, and 9.23 x 10(-8) (+/- 4.47 x 10(-7)) for levofloxacin. In serial
      transfer experiments, all isolates became resistant to clinically relevant levels
      of all fluoroquinolones after eight passages. The resistance occurred most
      rapidly with ciprofloxacin followed by grepafloxacin, gemifloxacin,
      trovafloxacin, and levofloxacin. These results show that strains with decreased
      susceptibility to fluoroquinolones occur frequently in cultures of Streptococcus
      pneumoniae, and this organism can readily become resistant to clinically relevant
      concentrations of fluoroquinolones in vitro.

PMID- 11837641
TI  - Tick-borne encephalitis virus in Lithuania.
AB  - Tick-borne encephalitis (TBE) is a severe problem in Lithuania, indicated by the
      171 to 645 serologically confirmed cases that occurred each year between 1993 and
      1999. In the present report, the first isolation and partial genetic analysis of
      a Lithuanian TBE virus (TBEV) strain isolated from a patient's serum sample is
      described. The patient was bitten by a tick while visiting the Lazdijai district
      (Veisiejai forest) in the southernmost part of Lithuania, a geographical area
      where Ixodes ricinus but not Ixodes persulcatus ticks are known to be present.
      The E protein-encoding viral gene sequence (nt 74-1273) recovered from the TBEV
      isolate showed the closest similarity to previously characterized European
      strains of the Western TBEV subtype, including the prototype TBEV strain
      Neudoerfl and those from neighbouring Latvia. Accordingly, the Lithuanian isolate
      was placed within the Western genetic lineage of TBEV in phylogenetic trees.

PMID- 11837642
TI  - Mycobacterium avium infection and immune restoration disease after highly active
      antiretroviral therapy in a patient with HIV and normal CD4+ counts.
AB  - A patient infected with HIV who had normal CD4+ T-cell counts developed
      Mycobacterium avium complex lymphadenitis associated with restoration of delayed
      type hypersensitivity responses to mycobacterial antigens after commencing highly
      active antiretroviral therapy (Mycobacterium avium immune restoration disease).
      This case provides further evidence that delayed-type hypersensitivity responses
      and CD4+ T-cell counts are independent indicators of the cellular immune defects
      induced by HIV infection and that Mycobacterium avium immune restoration disease
      may occur in patients with persistently normal CD4+ T-cell counts.

PMID- 11837643
TI  - Prospective follow-up of Epstein-Barr virus load in adult kidney transplant
      recipients by semiquantitative polymerase chain reaction in blood and saliva
      samples.
AB  - The aim of the study presented here was to set up and standardize a
      semiquantitative polymerase chain reaction method for monitoring Epstein-Barr
      virus (EBV) DNA levels in blood and saliva samples from transplant recipients and
      to determine the value of these levels as an early marker for the development of
      post-transplant lymphoproliferative disorders. EBV DNA load was prospectively
      measured in 53 adult kidney transplant recipients. Results were correlated with
      clinical features and degree of immunosuppression. Healthy blood donors and
      patients with infectious mononucleosis were used as controls. Levels higher than
      500 EBV DNA copies/75,000 peripheral blood mononuclear cells were found in all
      patients with infectious mononucleosis and in all patients with post-transplant
      lymphoproliferative disorder but in only 7.5% of transplant recipients without
      that complication.

PMID- 11837644
TI  - Possible mechanism of toxicity of zidovudine by induction of apoptosis of CD4+
      and CD8+ T-cells in vivo.
AB  - Some HIV-infected patients have a discordant response to highly active
      antiretroviral therapy with a low virus load and an incomplete restoration of
      CD4+ T-cell counts. Zidovudine may limit CD4+ restoration by a hematotoxic
      mechanism. Apoptosis and T-cell counts were assessed in two patients before and
      after they switched from zidovudine to stavudine. Whereas CD4+ T-cell apoptosis
      fell from 52% and 66% before the zidovudine switch to 7% and 12%, respectively,
      after the switch, the patients' CD4+ counts rose gradually to +183 and +150
      cells, respectively. It was therefore hypothesized that zidovudine directly
      induced apoptosis. Zidovudine withdrawal could be tested before immunological
      interventions such as interleukin-2 therapy are considered.

PMID- 11837645
TI  - Outbreak of Q fever among kitchen employees in an urban hospital.

PMID- 11837646
TI  - Emergence of high-level gentamicin resistance in group G streptococci.

PMID- 11837647
TI  - Detection and identification of spotted fever group rickettsiae in Dermacentor
      ticks from Russia and central Kazakhstan.

PMID- 11837648
TI  - Evaluation of a reverse hybridization blot test for detection of oxacillin
      resistant Staphylococcus aureus.

PMID- 11837649
TI  - A case of visceral leishmaniasis with protracted incubation in a nonendemic area.

PMID- 11837650
TI  - Fournier's gangrene in HIV-infected patients.

PMID- 11837651
TI  - Isolation of new alkylthiosulfides from the essential oil and extracts from the
      bark of Scorodophloeus zenkeri Harms.
AB  - 2,3,5-trithiahexane, 2,3,4,6-tetrathiaheptane, 2,4,5,7-tetrathiaoctane, two
      pentathianonanes, 2,4,5,7,9-pentathiadecane and two hexathiaundecanes were
      isolated from the essential oil and extracts from the bark of Scorodophloeus
      zenkeri Harms. Four other thioalkanes were found in small amounts in the
      essential oil.

PMID- 11837652
TI  - Chemical composition and biological activities of the Black Sea algae
      Polysiphonia denudata (Dillw.) Kutz. and Polysiphonia denudata f. fragilis
      (Sperk) Woronich.
AB  - The two investigated algae had almost identical sterol composition, but there
      were significant differences in the composition of the polar components and
      especially in the composition of the volatiles. P. denudata f. fragilis extracts
      possessed a stronger biological activity (antibacterial, antifungal and toxicity
      against Artemia salina). Despite the minute morphological differences between the
      two algae, we recommend P. denudata f. fragilis to be regarded as P. denudata
      subsp. fragilis.

PMID- 11837653
TI  - Properties of chlorophyllase from Capsicum annuum L. fruits.
AB  - The in vitro properties of semi-purified chlorophyllase (chlorophyll
      chlorophyllido hydrolase, EC 3.1.1.14) from Capsicum annuum fruits have been
      studied. The enzyme showed an optimum of activity at pH 8.5 and 50 degrees C.
      Substrate specificity was studied for chlorophyll (Chl) a, Chl b, pheophytin
      (Phe) a and Phe b, with Km values of 10.70, 4.04, 2.67 and 6.37 microM
      respectively. Substrate inhibition was found for Phe b at concentrations higher
      than 5 microM. Chlorophyllase action on Chl a' and Chl b' was also studied but no
      hydrolysis was observed, suggesting that the mechanism of action depends on the
      configuration at C-13(2) in the chlorophyll molecule, with the enzyme acting only
      on compounds with R132 stereochemistry. The effect of various metals (Mg2+, Hg2+,
      Cu2+, Zn2+ Co2+, Fe2+ and Fe3+) was also investigated, and a general inhibitory
      effect was found, this being more marked for Hg2+ and Fe2+. Functional groups
      such as -SH and -S-S- seemed to participate in the formation of the enzyme
      substrate complex. Chelating ion and the carbonyl group at C3 appeared to be
      important in substrate recognition by the enzyme. The method for measuring Chlase
      activity, including HPLC separation of substrate and product, has been optimized.

PMID- 11837654
TI  - Production and properties of a bacterial thermostable exo-inulinase.
AB  - Inulinase and Invertase Activities, Thermophilic Bacilli, Enzyme Thermostability
      Enzyme production of newly isolated thermophilic inulin-degrading Bacillus sp. 11
      strain was studied by batch cultivation in a fermentor. The achieved inulinase
      and invertase activities after a short growth time (4.25 h) were similar or
      higher compared to those reported for other mesophilic aerobic or anaerobic
      thermophilic bacterial producers and yeasts. The investigated enzyme belonged to
      the exo-type inulinases and splitted-off inulin, sucrose and raffinose. It could
      be used at temperatures above 65 degrees C and pH range 5.5-7.5. The obtained
      crude enzyme preparation possessed high thermostability. The residual inulinase
      and invertase activities were 92-98% after pretreatment at 65 degrees C for 60
      min in the presence of substrate inulin.

PMID- 11837655
TI  - Structure-activity relationship study of host-specific phytotoxins (AM-toxin
      analogs) using a new assay method with leaves from apple meristem culture.
AB  - AM-toxins are host-specific phytotoxins of the Alternaria alternata apple
      pathotype, which induce necrosis on apple leaves. In this study, we developed a
      new assay to measure the necrotic activity of AM-toxin analogs using cultured
      leaves from meristem cells. This method was not only more sensitive to AM-toxin
      I, but also more reliable than the previous one that used tree leaves due to the
      homogeneous nature of cultured leaves and to the method of application of toxins.
      Using this assay method we investigated a structure-activity relationship of AM
      toxin analogs synthesized in this study. Most residues and the macrocyclic ring
      structure were strictly recognized by AM-toxin putative receptor, whereas the L
      Ala binding subsite of the receptor allowed for side chain structures with
      various stereoelectronic properties. These findings are important for designing
      ligands for further experimental probing of the nature of the receptor.

PMID- 11837656
TI  - Activation of isoflavone biosynthesis in excised cotyledons of Lupinus seedlings
      by jasmonoids and excess light.
AB  - Exogenous jasmonic acid (JA) and methyl jasmonate (MJ) induced accumulation of
      isoflavone constituents in cotyledons prepared from imbibed seeds of white lupin
      (Lupinus albus L.). Exogenous 0.2 mM MJ enhanced the levels of 7-O-(6"-O
      malonyl)glucosylgenistein and 7-O-glucosylgenistein in the cotyledons of
      etiolated seedlings that had been incubated in the dark for 48 h. Regarding
      isoflavone induced by excision and slicing in the cotyledons as background level,
      the effect of light was 2- to 3-fold higher than that of 0.2 mM MJ. Cotyledons
      exposed to MJ along with a 24-h light period displayed a higher level of
      isoflavone accumulation than that of light alone. Total molar amounts of
      isoflavone accumulated in the cotyledons treated with MJ under continuous light
      were approximately the sum of those induced by MJ alone and light alone,
      respectively. The additive-like effect of MJ and light on isoflavone accumulation
      in lupin tissues suggested the presence of two different signaling systems
      independently responsible for those two stimuli. Excised cotyledons from
      etiolated yellow lupin (L. luteus L. cv. Topaz) seedlings also supported this
      hypothesis. The cotyledons could accumulate both an isoflavone and a flavone, and
      MJ selectively increased some of the isoflavone constituents, whereas light
      enhanced the levels of both. The selective accumulation mechanism of
      isoflavonoids in cotyledons, in which jasmonoids are involved, clearly differed
      from that activated by light.

PMID- 11837657
TI  - Fatty acid alteration of plastidic and extra-plastidic membrane lipids in
      metribuzin-resistant photoautotrophic Chenopodium rubrum cells as compared to
      wild-type cells.
AB  - The fatty acid compositions of plastidic and extra-plastidic membrane lipids of
      two metribuzin-resistant cell lines L4 and L7 of Chenopodium rubrum were
      determined after growth in the absence and in the presence of the herbicide and
      compared with those of wild type cells. Fatty acid biosynthesis was markedly
      affected in all cell lines by metribuzin treatment. In the absence and in the
      presence of metribuzin alterations of the fatty acid composition of the various
      lipid classes were, as compared to wild type cells, generally lower in the highly
      resistant L4 cells than in the less resistant L7 cells. The two resistant cell
      lines demonstrated a higher degree of unsaturation within the plastidic
      monogalactosyldiacylglycerols (L4 cells also within plastidic
      digalactosyldiacylglycerols) and, particularly, within the predominantly extra
      plastidic phosphatidylcholines (L7 cells also within the predominantly extra
      plastidic phosphatidylethanolamines), whereas the degree of unsaturation was
      slightly altered in the plastidic phosphatidylglycerols. Within the two
      metribuzin-resistant cell lines, the highly resistant L4 cells differed from the
      less resistant L7 cells by increased alpha-linolenic acid/palmitic acid ratios in
      both the plastidic and extra-plastidic membrane lipids suggesting that
      particularly in L4 cells higher proportions of linolenate are formed as a result
      of selection pressure. On the other hand, the proportion of linoleate was
      increased predominantly in extra-plastidic membrane lipids of both L4 and L7
      cells which explains a raise in linoleic acid/palmitic acid ratios in both cell
      lines as compared to wild-type cells. Moreover, in the absence of metribuzin
      decreased proportions of trans-3-hexadecenoic acid were found in
      phosphatidylglycerols of L4 and, particularly, of L7 cells as compared to the
      wild type cells. It is suggested that L4 and L7 cells--having multiple mutations
      in the psbA gene as observed earlier--are additionally characterized by increased
      degree of unsaturation of acyl moieties in various polar lipids, e.g. linoleoyl
      moieties in L4 and L7 cells as well as linolenoyl moieties particularly in highly
      resistant L4 cells. This increase gives rise to a change in membrane fluidity and
      may finally lead to increased metribuzin resistance.

PMID- 11837658
TI  - Interaction of quaternary ammonium and phosphonium salts with photosynthetic
      membranes.
AB  - Distinct concentration ranges of selected quaternary ammonium and phosphonium
      salts were elaborated to induce stimulatory or inhibitory effects, respectively,
      on photosynthetic reactions. By means of fluorescence induction measurements 3
      different effects of alkylbenzyldimethylammonium chloride (ABDAC; zephirol) in
      chloroplast preparations from Pisum sativum were observed. 60 microM ABDAC
      produced a strong increase in Fmax with concurrently improved Kautsky kinetics.
      Increased ABDAC concentration (500 microM) led to a strong fluorescence quenching
      - virtually indistinguishable from the conditions following the addition of
      photosystem II electron acceptors like K3Fe[CN]6. Further increase of ABDAC to 5
      mM provoked a drastic increase in the fluorescence yield together with the
      complete loss of any detectable kinetics. We suggest a 3-step interaction of
      ABDAC with the thylakoid membranes of photosynthetic organisms similar to our
      earlier discussion (Bader and Hoper (1993), Z. Naturforsch. 49c, 87-94). We
      examined a series of derivatives with selectively modified side chains, central
      atoms and counter ions, respectively. Both an alkyl chain of the type ([-CH2-]n;
      n approximately > 10) and effective polar components are indispensable for the
      adsorption and intercalation of the molecule onto and into the thylakoid
      membranes. The benzyl group could be replaced by a methyl residue without any
      loss of effectiveness; replacement of the central nitrogen (N) by phosphorus (P)
      and the counter ion Cl by Br did not modify the effects and the results were
      indistinguishable from the ABDAC effect proper. Shortening of the alkyl chain to
      (-CH2-)6 resulted in a less effective interaction of e.g. tetraoctylammonium
      bromide with the photosynthetic membrane. Flash-induced oxygen evolution
      measurements with selected derivatives (15 microm) substantiated our
      interpretation of an improved OEC functioning by a substantial lowering of the
      miss parameter a and the exclusion of a chemical reduction as the standard S
      state distribution was not affected. As evidenced by both SDS-PAGE and Western
      blot analyses the investigated molecules showed a direct interaction. The
      polypeptide patterns were characterized by a severe shift of the molecular weight
      components from high (20-67 kDa) to low (< 20 kDa) values.

PMID- 11837660
TI  - Relaxation of water protons in highly concentrated aqueous protein systems
      studied by 1H NMR spectroscopy.
AB  - Concentrated Aqueous Protein Systems, Proton Relaxation Times, Slow Chemical
      Exchange In this paper we present proton spin-lattice (T1) and spin-spin (T2)
      relaxation times measured vs. concentration, temperature, pulse interval
      (tauCPMG) as well as 1H NMR spectral measurements in a wide range of
      concentrations of bovine serum albumin (BSA) solutions. The anomalous relaxation
      behaviour of the water protons, similar to that observed in mammalian lenses, was
      found in the two most concentrated solutions (44% and 46%). The functional
      dependence of the spin-spin relaxation time vs. tauCPMG pulse interval and the
      values of the motional activation parameters obtained from the temperature
      dependencies of spin-lattice relaxation times suggest that the water molecule
      mobility is reduced in these systems. The slow exchange process on the T2 time
      scale is proposed to explain the obtained data. The proton spectral measurements
      support the hypothesis of a slow exchange mechanism in the highest concentrated
      solutions. From the analysis of the shape of the proton spectra the mean exchange
      times between bound and bulk water proton groups (tauex) have been estimated for
      the range of the highest concentrations (30%-46%). The obtained values are of the
      order of milliseconds assuring that the slow exchange condition is fulfilled in
      the most concentrated samples.

PMID- 11837659
TI  - Photosynthetic pigments, photosynthesis and plastid ultrastructure in RbcS
      antisense DNA mutants of tobacco (Nicotiana tabacum).
AB  - RbcS antisense DNA mutants of tobacco have reduced amounts of ribulose
      bisphosphate carboxylase oxygenase (Rubisco). We found that carotenoid and
      chlorophyll contents decrease in parallel as Rubisco is decreased, however,
      pigment levels are not significantly altered until Rubisco levels are reduced
      sharply. The mutants have normal Chl a/Chl b ratios and normal plastid
      ultrastructures, suggesting that reductions in Rubisco do not dramatically alter
      the composition of the thylakoid membranes. Nevertheless, chlorophyll
      fluorescence measurements, in which developmentally homogenous leaves were
      sampled, showed that there is reduced photosynthetic capacity of PSII and an
      enhanced photosensitivity in the mutants, especially in transgenics with severe
      reductions in Rubisco content. Support for this conclusion comes from several
      observations: 1) light saturation occurs at a lower light intensity in the
      mutants, resulting in an earlier closure of PS II (lower photochemical
      quenching); 2) the mutants have reduced photosynthetic efficiency (lower
      deltaF/Fm'); and 3) the mutants have a slower recovery of Fv/Fm. We found that
      acclimation to increasing light intensies in the mutants appears to involve an
      enhanced inactivation of PSII reaction centers as well as an increased activation
      of photoprotective mechanisms, notably an engagement of the xanthophyll cycle at
      lower than normal light intensities. We conclude that the photosensitivity of the
      antisense mutants is due, in part, to a limitation in Rubisco activation state.

PMID- 11837661
TI  - Enzyme activity of the cytochrome P-450 monooxygenase system in the presence of
      single chain lipid molecules.
AB  - The influence of single chain lipids on the 7-ethoxycoumarin O-deethyase activity
      of the reconstituted binary protein complex of isolated cytochrome P450 and NADPH
      cytochrome P450 reductase has been examined. The enzyme activity of this binary
      enzyme complex has been shown to be influenced by (i) altering the complexation
      process of both proteins, (ii) by altering the catalytic cycle time of the active
      binary protein complex and (iii) by altering the fraction of substrate molecules
      at the catalytic center of the enzyme. Competitive inhibition was measured for
      all single chain molecules. The following dissociation coefficients of substrate
      and lipids used for the catalytic center of the protein were obtained: 110 microM
      7-ethoxycoumarin (substrate), 1.1 microM MOG (1-monooleoyl-rac-glycerol), 0.3
      microM SPH (D-sphingosine), 1.5 microM OA (oleic acid), 3.0 microM LPC (L-alpha
      lysophosphatidyl-choline), 15.5 microM MSG (1-monostearoyl-rac-glycerol), 9.5
      microM AA (arachidonic acid), 9.0 microM PaCar (palmitoyl-L-carnitine), 3.5
      microM MPG (2-monopalmitoyl-glycerol), 1.5 microM LPI (L-alpha-lysophosphatidyl
      inositol), 50 microM LA (lauric acid), 60 microM MA (myristic acid), 85 microM PA
      (palmitic acid), >100 microM SA (stearic acid). Only competitive inhibition with
      the substrate molecule 7-ethoxycoumarin was observed for the single chain lipids
      LA, MA, PA, SPH, SA, and OA. Non-competitive effects were observed for MPG (-0.03
      microM(-1)), PaCar (-0.02 microM(-1)), MSG (-0.023 microM(-1)), LPC (-0.03
      microM(-1)), AA (-0.03 microM(-1)), and MOG (+0.04 microM(-1)). The negative sign
      indicates that the cycle time of the working binary complex is enlarged. The
      positive sign indicates that the formation of the binary complex is enhanced by
      MOG.

PMID- 11837662
TI  - Influence of the parasite Viscum cruciatum Sieber on the chemical constituents of
      Crataegus monogyna Jacq.
AB  - A phytochemical study of two plant species, Viscum cruciatum Sieber and Crataegus
      monogyna Jacq., was completed to investigate the influence of the parasite Viscum
      cruciatum on the host Crataegus monogyna. The study was carried out with two
      samples and consisted of hexane extracts of the Viscum cruciatum parasitizing on
      Crataegus monogyna and C monogyna. In these samples ursolic acid, beta-sitosterol
      and a triterpene fraction were found that contained mainly butyrospermol (3beta
      lanost 8, 24-dien, 3-ol), 24-methylene-24-dihydrolanosterol (24-methylene-5alpha
      lanost-8-en-3beta-ol), cycloartenol (9beta, 19-cyclo-5alpha, 9beta-lanost-24-en
      3beta-ol), beta-amyrin (olean-12-en-3beta-ol) and several aliphatic alcohols
      identified as the C18 to C30 members of the 1-alkanol homologous series. beta
      Amyrin acetate was only isolated from Viscum cruciatum and was not found in
      Crataegus monogyna.

PMID- 11837663
TI  - Biochemical and molecular biological studies on infection (Ascochyta rabiei)
      induced thaumatin-like proteins from chickpea plants (Cicer arietinum L.).
AB  - A pathogenesis-related protein induced by infection with Ascochyta rabiei was
      purified from intercellular washing fluid of chickpea (Cicer arietinum L.)
      leaves. Amino-terminal sequencing identified the protein, named PR-5a, as a
      thaumatin-like protein. The isoelectric point was determined with 6.5 and the
      molecular mass is 16 kDa. Therefore, chickpea PR-5a is the first dicot member of
      a TLP subgroup containing small TLPs with a molecular weight between 15 and 18
      kDa. PR-5a shows no antifungal activity towards A. rabiei. Screening of a
      chickpea cDNA library led to the isolation of a cDNA clone (p5a-241) for this
      protein. A second cDNA clone (ELR112) encoding a TLP was isolated using
      differential hybridisation of cDNA libraries obtained from elicited and water
      treated cell suspension cultures of chickpea. The deduced protein (PR-5b) has a
      molecular mass of 22 kDa. PR-5b is postulated to be located in the vacuole due to
      the presence of a respective N-terminal signal peptide and a carboxy-terminal
      extension. Southern blot analyses showed that ELR112 and p5a-241 represent single
      copy genes. During fungal infection of chickpea plants expression of both genes
      proceeds much faster in an A. rabiei resistant cultivar than in a susceptible
      one.

PMID- 11837664
TI  - The first glycosides isolated from propolis: diterpene rhamnosides.
AB  - Two diterpene glycosides, ent-8(17)-labden-15-O-alpha-L-rhamnoside and ent-8(17)
      labden-15-O-(3'-O-acetyl)-alpha-L-rhamnoside (new natural compounds) were
      isolated from propolis from El Salvador. The compounds showed significant
      antibacterial activity and moderate toxicity to Artemia salina nauplii. These are
      the first glycosides reported in bee glue.

PMID- 11837665
TI  - Antibacterial activity and chemical composition of Turkish propolis.
AB  - The antibacterial activities of propolis samples have been examined in vitro,
      according to the principles accepted for the determination of a similar activity
      of antibiotics with the use of solid and liquid media. It has been found that
      propolis extracts showed antibacterial activity through a range of commonly
      encountered gram positive cocci (S. aureus, beta hem. Streptococus), but had weak
      activity against gram negative bacteria (E. coli, P. aeruginosa). GC/MS analysis
      showed that propolis samples contain a variety of chemical compounds including
      aromatic compounds, fatty acid esters and sesquiterpenes.

PMID- 11837666
TI  - 11,17-dideoxyagelorin A and B, new bromotyrosine derivatives and analogs from the
      marine sponge Suberea aff. praetensa.
AB  - A collection of the marine sponge Suberea aff. praetensa from the Gulf of
      Thailand furnished the bromotyrosine derivatives fistularin-3, agelorins A and B
      and the new desoxyagelorins A and B.

PMID- 11837667
TI  - Sex attractants for six clearwing and tineid species (Lepidoptera, Sesiidae and
      Tineidae) from Kazakhstan and Lithuania.
AB  - Sex attractants for 3 Sesiidae and 3 Tineidae moth species in West-Kazakhstan and
      Lithuania were discovered by field screening tests of (3Z,13Z)-, (3E,13Z)- and
      (2E,13Z)-octadecadien-1-ols and their acetates as well as of some binary mixtures
      of these compounds. Total amount of chemicals was 0.3 mg/dispenser. Males of
      Synanthedon serica were attracted by a 5:5 mixture of 3E,13Z-18:OAc and 2E,13Z
      18:OAc, Chamaesphecia bibioniformis by a 9:1 mixture of 3Z,13Z-18:OAc and 3E,13Z
      18:OAc, Paranthrene tabaniformis by a 1:9 mixture of 3Z,13Z-18:OH and 3E,13Z
      18:OH, Tinea nonimella by a 1:9 mixture of 3E,13Z-18:OH and 2E,13Z-18:OH, Monopis
      monachella by a 1:9 mixture of 3Z,13Z-18:OH and 2E,13Z-18:OH, and Nemaxera
      betulinella by a 9:1 mixture of 2E,13Z-18:OAc and the corresponding alcohol. The
      periods of attraction to the traps were registered for males of S. serica and Ch.
      bibioniformis and were found to occur at 15-18 and 15-17 o'clock, local time,
      respectively.

PMID- 11837668
TI  - Identification of odoriferous compounds from adults of a swallowtail butterfly,
      Papilio machaon (Lepidoptera: Papilionidae).
AB  - Adults, particularly males, of a papilionid butterfly, Papilio machaon
      hippocrates, emit a fairly strong scent perceivable by humans. We have identified
      a variety of volatile compounds (hydrocarbons, alcohols, aldehydes, ketones,
      esters, and so on) from the wings and bodies of both sexes of the butterfly. Male
      wings secreted n-dodecane, linalool and geranylacetone as major components
      together with small amounts of camphene, limonene, p-cymene, 2-phenylethanol, n
      hexanal, n-decanal, isoamyl acetate, p-allylanisole, 2-pyrrolidone and other
      characteristic volatiles. The overall profile of volatile compounds detected from
      male body was quite different from that of the wings. Male body was devoid of
      camphene, 2-phenylethanol, n-hexanal but instead contained limonene, acetoin, a
      sesquiterpene hydrocarbon (C15H24, methyl n-octanoate, (E,E)-hepta-2,4-dienal,
      and another isomer of heptadienal as principal components, of which the last four
      compounds were specific to the body. All these substances seem to concurrently
      characterize the male odor. The chemical patterns of compounds found from female
      wings and body were essentially the same in quality as those of male wings and
      body, respectively, although their quantities in females were generally smaller
      than in males. Females, however, had a larger amount of acetamide than males. The
      chemical compositions of volatiles from the fore and hind wings of males were not
      greatly different from each other, and every component was considered to be
      present on all parts of the wings. This suggests that the scent-producing organs
      or scent-emitting pores are widely distributed on the whole wings. EAG responses
      of both sexes to 12 selected compounds identified from the butterfly were not
      strong at a dose of 1 microg, while both sexes showed relatively stronger
      responses to n-nonanal, methyl n-octanoate, D-limonene and linalool at a higher
      dose (10 microg). Although sexual difference in EAG response was not prominent,
      females appeared a little more sensitive, and n-nonanal and acetoin evoked
      significantly higher responses from females at 1 microg.

PMID- 11837669
TI  - Cross--reactivity of the V3-speciflc antibodies with the human C1q.
AB  - It has been previously shown that the sequence similarity between a portion of
      the envelope glycoprotein 120 (gp120) from the human immunodeficiency virus type
      1 (HIV-1) and several types of human collagen and collagen-like molecules exists.
      That observation led to the suggestion that the antibodies against the third
      hypervariable region (V3) of HIV-1 gp120 (V3-specific antibodies) might have a
      role in the autoimmune phenomena observed in HIV-infected persons. In this study
      we have examined the cross-reactivity of the V3-specific antibodies purified from
      sera of HIV-infected individuals, sera obtained from the rheumatoid arthritis and
      systemic lupus crythematosus patients, as well as from the sera of healthy
      volunteers with the separate chains of a subcomponent of the first component of
      the human complement system, Clq. Our results show that the V3-specific
      antibodies are present in the sera of the HIV-infected individuals, patients
      suffering of the systemic autoimmune diseases as well as in the sera of healthy
      volunteers. Whereas these antibodies appeared in the HIV+-sera after antigen
      challenge, those present in the HIV- -sera probably represent the antibodies that
      are cross-reactive with the antigen. V3-reactive antibodies can be purified by
      affinity chromatography and they were highly specific for the V3-peptide.
      Additionally, they showed cross-reactivity with the separate chains of the human
      Clq as well as with the chicken collagen type VI. Possible physiological
      implications are discussed.

PMID- 11837670
TI  - Alternative origin for "gain-of-function" by mutant SOD enzyme and for
      conformational change of normal prion protein.
AB  - Capillary electrophoresis and ESI-Mass spectrometry methods have revealed that a
      hydroperoxo-copper(II) complex with (tpa) (=tris(2-pyridylmethyl)amine) reacts
      with carbonic anhydrase or amyloid beta-peptide (1-40) as a nucleophile to induce
      the conformational change of the protein structure, while the Cu(bdpg)-complex
      ((bdpg)=N,N-bis(2-pyridylmethy)-beta-alanineamide) acts as an electrophile toward
      the proteins to degrade them under the same experimental conditions. This will
      lead to suggest that enhanced nucleophilic attack by a copper(II)-peroxide adduct
      to peptide bonding may be one of the serious origins for the "gain-of-function"
      by mutant superoxide dismutase and for conformational change of normal prion
      protein.

PMID- 11837672
TI  - Methemoglobin formation in human erythrocytes by nitroaromatic explosives.
AB  - We have examined the structure-activity relationships in methemoglobin (MetHb)
      formation by high explosives 2,4,6-trinitrotoluene (TNT), 2,4,6-trinitrophenyl-N
      nitramine (tetryl) and 2,4,6-trinitrophenyl-N-nitraminoethylnitrate (pentryl),
      and a number of model nitrobenzenes. In lysed human erythrocytes the rate
      constants of oxyhemoglobin (OxyHb) oxidation increased with an increase in single
      electron reduction potential (E(1)7) or with a decrease of the enthalpies of
      single-electron reduction of nitroaromatics. Tetryl and pentryl oxidized OxyHb
      almost 3 times faster than TNT. Although the initial rates of MetHb formation in
      intact erythrocytes by tetryl, pentryl, and TNT matched their order of reactivity
      in the oxidation of OxyHb in lysed erythrocytes, TNT was a more efficient MetHb
      forming agent than tetryl and pentryl during a 24-h incubation. The decreased
      efficiency of tetryl and pentryl was attributed to their reaction with
      intraerythrocyte reduced glutathione (GSH) producing 2,4,6-trinitrophenyl
      Sglutathione, which acted as a less efficient OxyHb oxidizing agent.

PMID- 11837671
TI  - Pancreatic phospholipase A2--mediated enhancement of the respiratory burst
      response of human neutrophils.
AB  - The aim of this study was to investigate the effects of exogenously added
      pancreatic phospholipase A2 (pPLA2) on the production of reactive oxygen species
      by human polymorphonuclear leukocytes (PMNs). Pancreatic PLA2 was used because
      PMNs do not possess a receptor for that enzyme and, therefore, the receptor
      mediated effects could be excluded. Respiratory burst activity of PMNs was
      monitored by luminol-amplified chemiluminescence and the lipid composition of
      neutrophils after treatment with pPLA2 was determined by matrix-assisted laser
      desorption/ionisation time-of-flight mass spectrometry. Our results show that the
      products of the pPLA2 digestion of the PMN membrane--lysophospholipids and the
      corresponding free fatty acids--significantly enhanced the respiratory burst
      response of human neutrophils.

PMID- 11837673
TI  - Accumulation of lignans in suspension cultures of Linum mucronatum ssp. armenum
      (Bordz.) Davis.
AB  - For the first time callus and suspension cultures of Linum mucronatum ssp.
      annenum were initiated, grown in darkness at 25 degrees C and analyzed for
      lignans. 6-Methoxypodophyllotoxin was the main lignan besides smaller amounts of
      podophyllotoxin isolated and identified by chromatographic methods as well as by
      1H NMR.

PMID- 11837674
TI  - Fluorescence studies on glyceraldehyde-3-phosphate dehydrogenase from bovine
      heart muscle.
AB  - Glyceraldehyde-3-phosphate dehydrogenase is a glycolytic enzyme that catalyses
      conversion of glyceraldehyde-3-phosphate to 1,3-diphosphoglycerate. ATP has been
      found to have an inhibitory effect on this enzyme. To establish the interaction
      between the enzyme and ATP, a fluorescence technique was used. Fluorescence
      quenching in the presence of ATP suggests cooperative binding of ATP to the
      enzyme (the Hill obtained coefficient equals 2.78). The interaction between
      glyceraldehyde-3-phosphate dehydrogenase and ATP may control not only glycolysis
      but other activities of this enzyme, such as binding to the cytoskeleton.

PMID- 11837675
TI  - Ischemia-responsive protein (irp94) is up-regulated by endoplasmic reticulum
      stress.
AB  - The expression of the ischemia-responsive protein (irp94) was enhanced by
      endoplasmic reticulum (ER) stress inducing drugs such as brefeldin A (BFA),
      calcium ionophor A23187, dithiothreitol (DTT) and tunicamycin in fisher rat
      thyroid epithelial cell line (FRTL-5 cells). In particular, irp94 mRNA expression
      was increased dose dependently by tunicamycin, and there was increased irp94
      expression when the cells were incubated with the thyroid-stimulating hormone
      (TSH) together.

PMID- 11837676
TI  - Changes of the brain synapses during aging. New aspects.
AB  - The process of brain aging is an interaction of age-related losses and
      compensatory mechanisms. This review is focused on the changes of the synaptic
      number and structure, their functional implications, regarding neurotransmission,
      as well as the electrical activity of neuronal circuits. Moreover, the importance
      of calcium homeostasis is strongly emphasized. It is also suggested that many
      neuronal properties are preserved, as a result of adaptive mechanisms, and that a
      series of interdependent factors regulate brain aging. The "new frontier" in
      research is the challenge of understanding the effects of aging, both to prevent
      degenerative diseases and reduce their consequences. New aspects are considered
      a) the role of nitric oxide, b) free radicals and apoptosis, c) impaired cerebral
      microcirculation, d) metabolic features of aging brain, e) the possible
      neuroprotective role of insulin-like growth factor-1 (IGF-1) and ovarian steroids
      and e) stress and aging. These numerous multifactorial approaches are essential
      to understand the process of aging. The more we learn about it, the more we
      realize how to achieve "successful" aging.

PMID- 11837677
TI  - Essential oil from herb and rhizome of Peucedanum ostruthium (L. Koch.) ex DC.
AB  - Essential oil from herb and rhizome of Peucedanum ostruthium (L.Koch.) ex DC
      underwent qualitative and quantitative analyses. The content of the oil obtained
      by hydrodistillation was 0.95% in the herb and 1.25% in the rhizome (per dry
      weight basis). Gas chromatography (GC) with MS detection and flame ionisation
      detection showed that the oil from the rhizome contains 39 compounds, of which 29
      were identified. Gas chromatography with flame ionisation detection in chiral
      columns against standard compounds showed the presence of enantiomers of some of
      the components of the oil. Compounds present in largest quantities are: sabinene
      (35.2%) of which (+) sabinene accounts for (96.54%) and 4-terpineol (26.6%) of
      which (+) 4-terpineol accounts for (65.8%). 44 components were found in the herb
      essential oil, of which 39 compounds were identified. Compounds present in
      largest quantities were beta-caryophyllene (16.1%) and alpha-humulene (15.8%).
      The content of sabinene in the herb oil was 4.7%. The following compounds were
      present in the herb oil only as enantiomers: (+) sabinene (4.7%), (-) limonene
      (4.4%), (-) beta-pinene (0.4%). A coumarin (osthole) was detected in both
      essential oils (5.5% in herb oil and 5.1% in rhizome oil).

PMID- 11837678
TI  - A new pyoverdin from Pseudomonas aeruginosa R'.
AB  - From a Pseudomonas aeruginosa hospital isolate a new pyoverdin was isolated. It
      is identical with that of Pseudomonas aeruginosa strain R except that in the
      peptide chain L-Gln is missing.

PMID- 11837679
TI  - Phytochemical and pharmacological analysis of Bauhinia microstachya (Raddi)
      Macbr. (Leguminosae).
AB  - This paper describes the isolation of four phytoconstituents from the leaves of
      Bauhinia microstachya, a Brazilian medicinal plant used in folk medicine for the
      treatment of several ailments. Based on spectroscopic evidence, these compounds
      were identified as methyl gallate (1), kaempferol 3-O-rhamnosyl (2), quercitrin
      (3) and myricitrin (4). The crude methanolic extract and two compounds (3 and 4)
      were tested as analgesic using the writhing test in mice. The extract and
      compound 3 caused potent and dose-related analgesic effects, confirming the
      popular use of this plant for the treatment dolorous processes.

PMID- 11837680
TI  - Phenolic acids and depsides from some species of the Erodium genera.
AB  - Six natural polyphenolic compounds, brevifolin carboxylic acid, brevifolin,
      ellagic acid, methyl gallate, gallic acid and protocatechuic acid have been
      isolated from the methanol extract of the whole plant of Erodium cicutarium (L.)
      L.'Herit. (Geraniaceae). Structures were determined by conventional methods of
      analysis and confirmed by MS and NMR spectral analysis. The distribution of these
      compounds in the other species of the Erodium genera (E. botrys, E. chium, E.
      ciconium, E. cicutarium, E. glutinosum subsp. dunense, E. gruinum, E. manescavi,
      E. pelargoniiflorum, E. petraeum) were examined by HPLC with a RP-18 column, and
      MGD-TLC methods on unmodified silica gel and silica gel chemically modified with
      polar and nonpolar groups (HPTLC-Si 60 LiChrospher, HPTLC-NH2, HPTLC-DIOL, HPTLC
      RP-18W).

PMID- 11837681
TI  - Chemistry of New Zealand Apiaceae: a rare phenylpropanoid and three new
      germacrane derivatives from Anisotome lyallii.
AB  - A phytochemical investigation of the New Zealand endemic Apiaceae species
      Anisotome lyallii Hook.f. yielded (+)-alpha-angeloyloxylatifolone (1), 6-O
      angeloyl-8-O-tigloyl-6beta,8alpha,11-trihydroxygermacra-1(10)E,4E-diene (2), 6-O
      tigloyl-8-O-tigloyl-6beta,8alpha,11-trihydroxygermacra-1(10)E,4E-diene (3) and 6
      O-tigloyl-8-O-tigloyl-1alpha,6beta,8alpha,11-tetrahydroxygermacra-4E,10-(14)diene
      (4). The structures were elucidated by HR mass spectrometry and 1D- and 2D-NMR
      spectroscopy. A chemosystematic survey for compounds 1-3 in other New Zealand
      Apiaceae by HPLC-MS revealed that 1-3 were confined to A. haastii Cockayne &
      Laing and A. lyallii, and that some minor compounds in other species of Anisotome
      were isomers of 2 and 3.

PMID- 11837682
TI  - Sesquiterpene lactones from Achillea chrysocoma and Achillea coarctata.
AB  - The aerial parts of A. chrysocoma and A. coarctata afforded 22 and 9
      sesquiterpene lactones, respectively. All the compounds described are new for the
      studied species. The lactones 5, 6 and 12 are new for the genus Achillea.

PMID- 11837683
TI  - Sesquiterpenoids and phenolics from Crepis conyzifolia.
AB  - From the roots of Crepis conyzifolia, two new and two known guaianolides were
      isolated together with three known phenylpropanoids. Structures of the new
      compounds were established as 8beta-hydroxy-4beta, 15-dihydrozaluzanin C and
      4beta, 15, 11beta, 13-tetrahydrozaluzanin C-3-O-beta-glucopyranoside by spectral
      methods. The identity of 8-epiisolippidiol and dentalactone was also discussed.

PMID- 11837684
TI  - Iridoids from Avicennia marina.
AB  - Three new iridoid glucosides, 10-O-[(E)-cinnamoyl]-geniposidic acid, 10-O-[(E)-p
      coumaroyl]-geniposidic acid, 10-O-[(E)-caffeoyl]-geniposidic acid and the known
      iridoid glucoside, 2'-O-[(E)-cinnamoyl]-mussaenosidic acid have been isolated
      from Avicennia marina. The structures were determined primarily by NMR
      spectroscopy. The assignment of NMR signals was performed by means of 1H-1H COSY,
      HMQC and HMBC experiments.

PMID- 11837685
TI  - Chromene chalcones from Tephrosia carrollii and the revised structure of
      Oaracacin.
AB  - The aerial parts of Tephrosia carrollii afforded two chromene chalcones. Their
      structures and stereochemistry were established by spectroscopic methods. The
      structure of oaxacacin was revised and confirmed by X-ray diffraction. In this
      paper, we describe the isolation of the chalcone known as "oaxacacin" and the new
      chalcone named epoxyobovatachalcone. The compound der. oaxacacin was found to be
      identical with obovatachalcone based on spectroscopic evidence and X-ray
      diffraction.

PMID- 11837686
TI  - Total phenolics concentration and antioxidant potential of extracts of medicinal
      plants of Pakistan.
AB  - Thirty-seven plant organs, traditionally used as drugs, collected in Pakistan,
      were extracted with 70% acetone and analyzed for their total phenolics
      concentration and antioxidant potential. Seven extracts showed more than 85%
      inhibition of lipid peroxidation in vitro as compared with blank. Butylated
      hydroxytoluene (BHT) (IC50 = 233.6 microg/l +/- 28.3) was the strongest
      antioxidant in our test system. The IC50 results indicate that the extracts of
      Nymphaea lotus L. flowers, Acacia nilotica (Linn.) Delile beans, Terminalia
      belerica Roxb. fruits, and Terminalia chebula Retz. (fruits, brown) were stronger
      antioxidants than alpha-tocopherol, while Terminalia chebula Retz. (fruit coat),
      Terminalia chebula Retz. (fruits, black) and Ricinus communis L. leaves were
      weaker antioxidant extracts than alpha-tocopherol and BHT. Total phenolics
      concentration, expressed as gallic acid equivalents, showed close correlation
      with the antioxidant activity. High performance liquid chromatographic analysis
      with diode array detection at 280 nm, of the seven extracts indicated the
      presence of hydroxybenzoic acid derivatives, hydroxycinnamic acid derivatives,
      flavonol aglycones and their glycosides as main phenolics compounds. This
      information, based on quick screening methods, enables us to proceed towards more
      detailed chemical and pharmacological understanding of these plant materials.

PMID- 11837688
TI  - Two novel phenylacetoxylated p-terphenyls from Thelephora ganbajun Zang.
AB  - Two novel phenylacetoxylated p-terphenyl derivatives, namely ganbajunin F (6'
      methoxy-2'-phenylacetoxy-3', 4, 4", 5'-tetrahydroxy- p-terphenyl), and ganbajunin
      G (5'-methoxy-2'-phenylacetoxy-3', 4, 4", 6'-tetrahydroxy-p-terphenyl), together
      with a known compound cycloleucomelone were isolated from the fruiting bodies of
      Thelephora ganbajun Zang. Their structures were established on the basis of
      spectral (MS, IR, NMR, HMBC, HMQC measurement) and chemical evidence.

PMID- 11837687
TI  - Chemical analysis and antimicrobial activity of Halimium voldii.
AB  - Volatile constituents and a hexane extract of the leaves of Halimium voldii Kit
      Tan, Perdetzoglou & Raus, sp. nova, were analyzed by GC and GC-MS. Thirty
      compounds were identified in the essential oil of Halimium representing 88.7% of
      the oil composition. The main components were nonanal (12.8%), dodecane (10.6%),
      Z-caryophyllene (8.2%), gamma-muurolene (10.9%), delta-cadidene (3.5%),
      caryophyllene oxide (5.1%), beta-eudesmol (3.6%) and manoyl oxide (5.5%). Thymol
      was identified in the hexane extract as the main compound. A labdane diterpene
      ent-labd-7, 13 (E)-dien, 15-ol was detected by its mass spectra fragmentation
      pattern and its structure was determined by spectroscopic methods and its optical
      rotation. The essential oil and the hexane extract were assayed for their
      antimicrobial activity against gram (+) and gram (-) bacteria.

PMID- 11837689
TI  - Limnantheoside C (20-hydroxyecdysone 3-O-beta-D-glucopyranosyl-[1-->3]-beta-D
      xylopyranoside), a phytoecdysteroid from seeds of Limnanthes alba
      (limnanthaceae).
AB  - A new ecdysteroid glycoside, limnantheoside C (20-hydroxyecdysone 3-O-beta-D
      glucopyranosyl-[-->3]-beta-D-xylopyranoside [1]), together with limnantheoside A
      (20-hydroxyecdysone 3-O-beta-D-xylopyranoside [2]) and 20-hydroxyecdysone (3)
      have been isolated by bioassay/RIA-directed HPLC analyses of a methanol extract
      of the seedmeal of Limnanthes alba Hartw. ex Benth. The structure of the novel
      ecdysteroid glycoside (1) was determined unambiguously by UV, LSIMS and a
      combination of 1D- and 2D-NMR experiments. These three compounds are isolated
      from Limnanthes alba for the first time.

PMID- 11837690
TI  - Physiological activity of some aminophosphonates.
AB  - Influence of some new aminophosphonates on electrolyte leakage from cucumber
      (Cucumis sativus cv "Wisconsin") cotyledons as well as on the content of
      chlorophyll and activity of guaiacol and pyrogallol peroxidase were studied.
      Concentration of malondialdehyde (MDA), one of the end-products of lipid
      peroxidation, was also measured. It was found that aminophosphates influenced the
      parameters observed to various extents, depending on their structural features
      and the concentration used. Most active modifiers were those possessing
      sufficiently long hydrocarbon substituents at the nitrogen atom and/ or iso
      propyl chain at the phosphorus atom.

PMID- 11837691
TI  - Physiological activity of some organophosphorous compounds and their influence on
      mechanical properties of erythrocytes.
AB  - Hemolysis and fluidization of erythrocytes (RBC) membranes by some newly
      synthesized aminophosphonates as well as their potency to induce electrolyte
      efflux from cucumber (Cucumis sativus cv "Wisconsin") cotyledons were studied.
      Also, the chlorophyll content in aminophosphonate-treated cotyledons was
      affected. The compounds studied differed mainly in hydrophobicity of their
      substituents at the carbon, nitrogen and phosphorus atoms. It was found that
      aminophosphonate potency to fluidize RBC membranes depended on the combination of
      its overall lipophilicity and/or the kind of substituent at the P atom.
      Especially, iso-propyl groups enhanced that potency. The sequence of
      aminophosphonates that exhibited the strongest fluidization activity was
      paralelled by their physiological and hemolytic activities; in the latter case
      for these compounds that hemolyzed RBC under used concentrations. A general
      conclusion is that both the stereochemistry and lipophilicity determine the
      efficiency of the aminophosphonates studied. This efficiency is most probably
      related to the interaction of aminophosphonates with the lipid phase of
      biological objects.

PMID- 11837693
TI  - Multiple receptor liquid chromatographic stationary phases: the co-immobilization
      of nicotinic receptors, gamma-amino-butyric acid receptors, and N-methyl D
      aspartate receptors.

PMID- 11837692
TI  - Validity of in vitro tests on aqueous spray pumps as surrogates for nasal
      deposition.
AB  - PURPOSE: To determine whether deposition pattern is related to in vitro
      measurements of droplet size, plume geometry, and spray pattern between two
      different nasal spray pumps believed to have different performance
      characteristics. METHODS: Ten healthy volunteers inhaled radiolabeled saline from
      two different spray pumps (pump A and pump B). Deposition pattern was quantified
      from lateral views of the nose by gamma scintigraphy, expressed as the ratio of
      anterior to posterior (I:O) and superior to inferior (U:L) deposition. Droplet
      size was determined by Malvern Mastersizer S. Spray patterns were determined at
      2.5 and 5 cm from the tip of the spray nozzle. Two-dimensional images of the
      emitted plume were captured by high-speed still photography. RESULTS: There were
      no significant differences in I:O or U:L ratios for pump A compared to pump B,
      indicating no significant differences in deposition pattern. The volume
      diameters, Dv10 and Dv50, were not statistically different for pump A compared to
      pump B. There was a significant difference in Dv90 between pump A and pump B,
      (86.9 +/- 5.8 microm and 77.4 +/- 2.4 microm. respectively; P < 0.001). The ratio
      of the longest to shortest diameter for the spray pattern with pump A was 1.26 +/
      0.06 at 2.5 cm and 1.44 +/- 0.08 at 5 cm. The ratio for pump B was 1.13 +/- 0.03
      at 2.5 cm and 1.19 +/- 0.05 at 5 cm. Ratios at both heights were statistically
      different for pump A compared to pump B (P < 0.00002 and P < 0.000001,
      respectively) Plume geometry analysis indicated statistical differences in both
      the width (17.0 +/- 0.97 vs. 18.5 +/- 0.56 cm, respectively: p<0.001) and the
      maximum length of the plumes (46.0 +/- 1.83 vs. 53.1 +/- 4.88 cm, respectively; p
      < .002). The differences in velocity of the plume and spray angle between the two
      pumps were not statistically different. CONCLUSIONS. Certain in vitro tests
      detected performance differences between the two pumps. However, these
      differences did not translate into different deposition patterns in vivo.

PMID- 11837694
TI  - Cyclosporine A formulation affects its ocular distribution in rabbits.

PMID- 11837695
TI  - Physicochemical characterization and solubility analysis of thalidomide and its N
      alkyl analogs.
AB  - PURPOSE: The present study was primarily aimed at exploring the feasibility of
      improving percutaneous delivery via chemical manipulation of the thalidomide
      molecule to form analogs with improved physicochemical properties. N-Alkyl
      analogs were synthesized with the belief that these would be suitably hydrophobic
      and far less crystalline than the reference compound. This article presents their
      physicochemical properties. METHODS: Thalidomide and three of its N-alkyl analogs
      were synthesized. Identification and levels of purity (>96%) were assured through
      element analysis, fast atom-bombardment mass spectrometry, nuclear magnetic
      resonance spectroscopy, and high-performance liquid chromatography. N
      Octanol/water partition coefficients were determined at pH 6.4. Solubilities in
      water and a series of n-alkanols were obtained. Best-fit solubility parameters
      were determined from the solubilities of the respective compounds in London
      solvents and were also calculated from respective hexane solubilities. melting
      points and heats of fusion. RESULTS: Methylation of the thalidomide molecule at
      its acidic nitrogen led to an aqueous solubility about 6-fold higher than
      thalidomide but, because the alkyl chain length was further extended from methyl
      to pentyl. aqueous solubilities decreased essentially exponentially. The
      destabilization of the crystalline structure with increasing alkyl chain length
      led to an increased solubility in nonpolar media. The log partition coefficient
      increased linearly with increasing alkyl chain length and the solubility
      parameters declined systematically through this series. By adding a methyl group
      to the thalidomide structure, the melting point dropped by more than 100 degrees
      C. Adding to the alkyl chain length led to further, more modest decreases. Heats
      of fusion decreased dramatically upon thalidomide's alkylation as well.
      CONCLUSION: Alkylation of the thalidomide molecule resulted in compounds with
      physicochemical properties that appear to be markedly better suited for
      percutaneous delivery.

PMID- 11837696
TI  - Effects of a citrate buffer system on the solid-state chemical stability of
      lyophilized quinapril preparations.
AB  - PURPOSE: The objective of this study was to examine the effect of a citric acid
      citrate buffer system on the chemical instability of lyophilized amorphous
      samples of quinapril hydrochloride (QHCI). METHODS: Molecular dispersions of QHCI
      and citric acid were prepared by colyophilization from their corresponding
      aqueous solutions with a molar ratio of QHCI to citric acid from 1:1 to 6:1 and
      solution pH from 2.49 to 3.05. Solid samples were subjected to a temperature of
      80 degrees C and were analyzed for degradation using high-performance liquid
      chromatography. The glass transition temperature, Tg, of all samples was measured
      by differential scanning calorimetry. RESULTS: Samples were first examined by
      varying the Tg and maintaining the initial solution pH constant. At pH 2.49 the
      rate of reaction was found to be less dependent on the sample Tg, whereas at pH >
      or = 2.75 the rate decreased with an increase in Tg. In a second set of
      experiments at a constant Tg of approximately 70 degrees C, the reaction rate
      increased as the pH increased. CONCLUSION: The overall solid-state chemical
      reactivity of amorphous quinapril depends on the relative amount of QHCI and Q+-,
      the zwitterionic form of quinapril. At high proportions of Q+- (higher pH values)
      the reaction rate seems to be strongly influenced by the Tg of the mixture, and
      hence the molecular mobility, whereas at higher proportions of QHCI (lower pH)
      the reaction rate is less sensitive to Tg, presumably because of different
      mechanistic rate determining steps for the two sets of conditions.

PMID- 11837697
TI  - Comparison of bidirectional cephalexin transport across MDCK and caco-2 cell
      monolayers: interactions with peptide transporters.
AB  - PURPOSE: Bidirectional transport studies were conducted to determine whether
      Madin-Darby canine kidney (MDCK) cell monolayers could be used as an alternative
      to the traditional Caco-2 assay as a fast-growing in vitro model of peptide
      transport. METHODS: Transport of cephalexin and glycylsarcosine across MDCK and
      Caco-2 cell monolayers was quantified using LC-LC/MS. Glycylsarcosine, p
      aminohippuric acid (PAH), and tetraethylammonium chloride (TEA) were tested as
      inhibitors of cephalexin transport. RESULTS: The ratio of apparent cephalexin
      permeabilities (apical to basolateral/basolateral to apical) obtained from MDCK
      monolayers was almost 5-fold greater than that obtained from Caco-2 monolayers.
      The opposite trend was observed for glycylsarcosine. When MDCK monolayers were
      used, glycylsarcosine reduced the cephalexin/apparent permeability ratio almost
      90%. PAH and TEA did not inhibit cephalexin transport across MDCK or Caco-2 cell
      monolayers. CONCLUSION: MDCK cell monolayers may be a promising, fast-growing
      alternative to Caco-2 cells for identifying peptide transporter substrates.
      However, differences in the apical-to-basolateral transport of cephalexin and
      glycylsarcosine suggest that the basolateral transport mechanisms for these
      compounds are different in the two cell lines. Additionally, because the activity
      of the peptide transporter in MDCK cells was low, scaling factors may be required
      when using this cell line to predict in vivo drug absorption.

PMID- 11837698
TI  - Transport activity of human MRP3 expressed in Sf9 cells: comparative studies with
      rat MRP3.
AB  - PURPOSE: Multidrug resistance-associated protein 3 (MRP3) was initially cloned as
      a hepatic transporter induced under cholestatic/ hyperbilirubinemic conditions.
      In the present study, transport property of human MRP3 (hMRP3) was compared with
      that of rat MRP3 (rMRP3). METHODS: Adenosine 5' triphosphate (ATP)-dependent
      uptake of several organic anions into the membrane vesicles isolated from the Sf9
      cells expressing hMRP3 and rMRP3 was measured by rapid filtration technique.
      RESULTS: ATP-dependent uptake of glucuronide conjugates, glutathione conjugates.
      and [3H]methotrexate (MTX) was stimulated by infection of cDNAs for hMRP3 and
      rMRP3. The mean (+/- SE) Km values for the uptake of 17beta estradiol 17beta-D
      glucuronide ([3H]E(2)17 betaG) by hMRP3 and rMRP3 were 42.9 +/- 4.3 microM and
      33.4 +/- 2.2 microM, respectively. Although the Ki values of glucuronides on the
      uptake of E217betaG were similar in humans and rats, hMRP3 exhibited higher Ki
      values toward MTX. In addition, although glycocholate and taurolithocholate 3
      sulfate (TLC-S) were transported by both hMRP3 and rMRP3, taurocholate was only
      transported to a significant degree by rMRP3. Moreover, the inhibitory effect of
      taurocholate and glycocholate on the transport of E(2)17beta3G was much more
      potent in rMRP3 compared to hMRP3. CONCLUSION: Collectively, the substrate
      specificity of hMRP3 resembles that of rMRP3 although differences were observed,
      particularly in bile acid transport.

PMID- 11837699
TI  - Influence of hydrodynamics and particle size on the absorption of felodipine in
      labradors.
AB  - PURPOSE: To study the influence of GI hydrodynamics and drug particle size on
      felodipine absorption in the dog. METHODS: Labradors fistulated at midjejunum
      were used to selectively study the influence of hydrodynamics and particle size
      on the in vivo dissolution and absorption of the poorly soluble, lipophilic drug
      felodipine. A combination of infusion and oral administration of either normal
      saline or a 5% glucose solution was used to maintain "fasted" and establish "fed"
      state motility patterns, respectively. The absorption characteristics of both a
      micronized (8 microm) and a coarse fraction (125 micom) of felodipine were
      subsequently studied under these two motility patterns. RESULTS: A reduction in
      particle size led up to an approximate 22-fold increase in maximum plasma
      concentration and up to an approximate 14-fold increase in area under the curve,
      with a commensurate decrease in the time at which the maximum plasma
      concentration occurred. Although the absorption of felodipine from the solution
      and micronized suspension was not influenced by a change in the hydrodynamics,
      felodipine was absorbed from the coarse suspension almost twice as well in the
      "fed" state as under "fasted" conditions. CONCLUSIONS: Absorption from coarse
      suspensions of felodipine was sensitive to luminal hydrodynamics, whereas
      micronized suspensions were not. However, the particle size seems to have a much
      more important influence on the bioavailability of felodipine than the
      hydrodynamics per se.

PMID- 11837700
TI  - Development and application of an isolated perfused rat liver model to study the
      stimulation and inhibition of tumor necrosis factor-alpha production ex vivo.
AB  - PURPOSE: To develop an isolated perfused rat liver (IPRL) model with low baseline
      levels of tumor necrosis factor (TNF)-alpha in the outlet perfusate to study the
      effects of immunostimulants and immunosuppressants on the release of TNF-alpha
      from this organ. METHODS: Isolated rat livers were perfused with a buffer
      containing no albumin or three different bovine serum albumin (BSA) preparations.
      Using the no-albumin perfusate, the inhibitory effects of methylprednisolone (MP)
      on lipopolysaccharide (LPS)-stimulated release of TNF-alpha were studied in
      livers isolated 1 or 5 h after the intravenous administration (5 mg/kg) of MP.
      The concentrations of TNF-a in the outlet perfusates were measured using enzyme
      linked immunosorbent assay. RESULTS: In the absence of albumin, the perfusate
      levels of TNF-alpha were close to zero. However, when the perfusate contained
      BSA. the TNF-alpha levels in the perfusate reached as high as 1200 pg/ml at
      steady state. An injection of LPS into IPRLs perfused with a no-albumin perfusate
      resulted in mean (+/- SD) TNF-alpha steady-state concentrations of 825 +/- 125
      pg/ml. The pretreatment of rats with MP before liver harvest attenuated the LPS
      induced TNF-alpha release in the livers. However, the attenuation was substantial
      (>60%) and was statistically significant only 5 h after pretreatment with MP.
      CONCLUSIONS: Perfusates containing BSA may result in nonphysiologically high
      levels of TNF-alpha. An IPRL with a no-albumin perfusate is more suitable for
      studies of the stimulation and inhibition of TNF-alpha production by this organ.

PMID- 11837701
TI  - Macroflux microprojection array patch technology: a new and efficient approach
      for intracutaneous immunization.
AB  - PURPOSE: We evaluated the Macroflux microprojection array patch technology as a
      novel system for intracutaneous delivery of protein antigens. METHODS: Macroflux
      microprojection array systems (330-microm micro-projection length, 190
      microprojections/cm2, 1- and 2-cm2 area) were coated with a model protein
      antigen, ovalbumin (OVA), to produce a dry-film coating. After system
      application, microprojection penetration depth, OVA delivery, and comparative
      immune responses were evaluated in a hairless guinea pig model. RESULTS:
      Macroflux microprojections penetrated into hairless guinea pig skin at an average
      depth of 100 microm with no projections deeper than 300 microm. Doses of I to 80
      microg of OVA were delivered via 1- or 2-cm2 systems by varying the coating
      solution concentration and wearing time. Delivery rates were as high as 20 microg
      in 5 s. In a prime and boost dose immune response study, OVA-coated Macroflux was
      most comparable to equivalent doses injected intradermally. Higher antibody
      titers were observed when OVA was administered with the microprojection array or
      intradermally at low doses (1 and 5 microg). Macroflux administration at 1- and 5
      microg doses gave immune responses up to 50-fold greater than that observed after
      the same subcutaneous or intramuscular dose. Dry coating an adjuvant,
      glucosaminyl muramyl dipeptide, with OVA on the Macroflux resulted in augmented
      antibody responses. CONCLUSIONS: Macroflux skin patch technology provides rapid
      and reproducible intracutaneous administration of dry-coated antigen. The depth
      of skin penetration targets skin immune cells; the quantity of antigen delivered
      can be controlled by formulation, patch wearing time, and system size. This novel
      needle-free patch technology may ultimately have broad applications for a wide
      variety of therapeutic vaccines to improve efficacy and convenience of use.

PMID- 11837702
TI  - Increase in the specific surface area of budesonide during storage
      postmicronization.
AB  - PURPOSE: To evaluate an anomalous increase in the specific surface area of
      budesonide during storage postmicronization. METHODS: Budesonide was micronized
      using a conventional air-jet mill. Surface areas and total pore volumes were
      measured using nitrogen sorption. Porosity was measured using mercury intrusion
      porosimetry. Particle size was measured using laser diffraction. RESULTS:
      Budesonide exhibited a surface area increase of 22 +/- 2% when stored at 25
      degrees C following micronization. The rate of surface area increase was lower at
      20 degrees C. suggesting a temperature-dependent stress relaxation mechanism for
      the micronized particles. The increase in surface area was accompanied by: (a) an
      increase in total pore volume: (b) a shift of the pore size distribution to
      smaller pore sizes; (c) a decrease in size of particles above approximately 1
      microm; and (d) an increase in rugosity/surface roughness. CONCLUSIONS: Freshly
      micronized budesonide exhibited an unusual and significant postmicronization
      increase in specific surface area upon storage under ambient conditions.
      Postmicronization stress-relief by intraparticle crack formation, crack
      propagation with time, and particle fracture seems to be the primary mechanism
      behind this surface area increase.

PMID- 11837703
TI  - Improved antioxidant effect of idebenone-loaded polyethyl-2-cyanoacrylate
      nanocapsules tested on human fibroblasts.
AB  - PURPOSE: The protective antioxidant role of idebenone both as free drug and drug
      loaded Tween 80-coated polyethyl-2-cyanoacrylate (PECA) nanocapsules is reported.
      The relationship between oxidative damage and apoptotic or nonapoptotic cell
      death is evaluated in vitro. METHODS: Idebenone-loaded nanocapsules were prepared
      with the interfacial polymerization method in the presence of Tween 80. Human
      nonimmortalized fibroblasts. under different stress conditions, either 0.5 mM
      diethylmaleate (DEM) for 60 min or 0.1 mM H2O2 for 30 min, were used as the
      experimental in vitro model. The production of reactive oxygen species, the cell
      viability, and the nuclear DNA damage were evaluated. The presence of apoptotic
      damage was evaluated both by the determination of caspase-3-like protein activity
      and by Promega's fluorescent apoptotic detection system. RESULTS: DEM and H2O2
      affected the cultured cells in different ways. DEM induced a moderate cellular
      insult, which was efficaciously antagonized by idebenone-loaded PECA
      nanocapsules. H2O2 elicited severe damage to nuclear DNA, which was reduced by
      idebenoneloaded PECA nanocapsules. The free drug was less effective than
      idebenone-loaded nanocapsules. CONCLUSIONS: The findings reported here
      demonstrate that an improved antioxidant effect was obtained with a low idebenone
      concentration (0.5 microM) when the drug was entrapped within Tween 80-coated
      PECA nanocapsules.

PMID- 11837704
TI  - Arsonoliposomes, a novel class of arsenic-containing liposomes: effect of
      palmitoyl-arsonolipid-containing liposomes on the viability of cancer and normal
      cells in culture.
AB  - PURPOSE: Arsonolipid-containing liposomes have been recently prepared. The
      demonstrated antileukemic action of arsenic trioxide prompted us to study their
      effect on the viability of several types of cancer cells to investigate the
      possibility of relevant applications. Five different cell types, three malignant
      (HL-60, C6. and GH3) and two non-malignant (HUVEC and RAME), were used. METHODS:
      Liposomes containing the palmitoyl side chain arsonolipid (with different lipid
      compositions) were incubated with a given number of cells. Cell viability was
      estimated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-dimethyltetrazolium bromide
      assay. Morphologic studies were also performed. RESULTS: Our results reveal that
      arsonoliposomes cause a dose (initiated at 10(-6) M)- and time-dependent
      inhibition of survival in all three malignant cell lines studied. No significant
      effect on the survival of the normal cells studied was observed at these, as well
      as at 10-fold higher. concentrations, although arsenic trioxide was toxic to
      HUVEC cells at equivalent arsenic concentrations. Microscopy studies reveal that
      although morphologic changes were initiated in HL-60 and C6 cells after
      incubation with arsonoliposomes, no changes in HUVEC and RAME cells were
      observed. CONCLUSIONS: Considering the numerous advantages of liposomal systems
      in therapeutics, it is concluded that the arsonoliposome system is very
      interesting and future applications should be exploited by further studies.

PMID- 11837706
TI  - In silico prediction of optimal in vivo delivery properties using convolution
      based model and clinical trial simulation.
AB  - PURPOSE: To develop a new strategy for the in silico evaluation of the optimal in
      vivo delivery properties of a drug, minimizing a cost function defined by the
      brain receptor occupancy obtained in positron-emission tomography experiments.
      METHODS: A convolution-based model was formulated to link in vivo delivery rate
      to plasma concentrations whereas a second-stage model was used to link plasma
      concentrations to the pharmacodynamic effect. A feedback control approach was
      applied to identify the optimal in vivo delivery rate given an appropriate
      optimality criterion. Finally, clinical trial simulation was used as a supportive
      tool for decision-making by evaluating different scenarios accounting for
      pharmacokinetic/pharmacodynamic parameter uncertainty, inter-subject variability.
      and drug potency. RESULTS: The results revealed that the mean in vivo delivery
      time significantly affects brain receptor occupancy whereas the fraction of the
      dose available for the systemic circulation shows the highest influence on brain
      receptor occupancy for a given in vivo delivery rate. Finally, variability on
      receptor occupancy seems to be more affected by the inter-individual variability
      on the disposition PK parameters. CONCLUSION: The integration of convolution
      based model. feedback control approach, and clinical trial simulation offers a
      unique tool for in ilico improvement of the drug development process by
      identifying critical issues on drug properties, optimal in vivo delivery rate,
      and potential problems related to the inter-individual variability.

PMID- 11837705
TI  - Modeling the pharmacokinetics and pharmacodynamics of a unique oral hypoglycemic
      agent using neural networks.
AB  - PURPOSE: To develop a predictive population pharmacokinetic/ pharmacodynamic
      (PK/PD) model for repaglinide (REP), an oral hypoglycemic agent, using artificial
      neural networks (ANNs). METHODS: REP, glucose concentrations, and demographic
      data from a dose ranging Phase 2 trial were divided into a training set (70%) and
      a test set (30%). NeuroShell Predictor was used to create predictive PK and PK/PD
      models using population covariates: evaluate the relative significance of
      different covariates; and simulate the effect of covariates on the PK/PD of REP.
      Predictive performance was evaluated by calculating root mean square error and
      mean error for the training and test sets. These values were compared to naive
      averaging (NA) and randomly generated numbers (RN). RESULTS: Covariates found to
      have an influence on PK of REP include dose, gender. race, age, and weight.
      Covariates affecting the glucose response included dose, gender, and weight.
      These differences are not expected to be clinically significant. CONCLUSIONS: We
      came to the following three conclusions: 1) ANNs are more precise than NA and RN
      for both PK and PD; 2) the bias was acceptable for ANNs as compared with NA and
      RN; and 3) neural networks offer a quick and simple method for predicting, for
      identifying significant covariates, and for generating hypotheses.

PMID- 11837707
TI  - Usage of supplemental alternative medicine by community-based patients with
      gastroesophageal reflux disease (GERD).
AB  - There is an increasing trend towards alternative medicine usage by the general US
      population. However, the extent and type of supplemental alternative medicine
      used specifically by community-based patients with GERD is unknown. A previously
      validated questionnaire that included questions about patient demographics, 18
      types of alternative medicine, and attitudes towards alternative and conventional
      medicine was utilized. Consecutive patients seen by community-based physicians in
      Arizona (Tucson, Phoenix, and Flagstaff) and Wisconsin (Milwaukee) for GERD
      received the questionnaire during the years 1999 and 2000. Patients completed the
      questionnaire and returned it to the Tucson VA Medical Center by mail. A total of
      185 patients were surveyed (82 men, mean age 55.8 years). Of those, 61.6% used
      alternative medicine for any reason. However, only 3.8% of patients used
      supplemental alternative medicine for GERD. Females were twice as likely (95% CI,
      1.10-3.67) to use alternative medicines for any reason (including GERD). Patients
      with daily acid regurgitation were 5.75 times (95% CI, 1.03-32.17) more likely
      than patients with less frequent acid regurgitation to use alternative medicines
      specifically for GERD. None of the other demographics, health characteristics, or
      attitudes were predictive of supplemental alternative medicine use for any reason
      (or specifically for GERD). In conclusion, only a small percentage of GERD
      patients seen by community-based practitioners use supplemental alternative
      medicine specifically for GERD symptoms, despite a higher usage of supplemental
      alternative medicine for non-GERD-related illness. Being female and having acid
      regurgitation daily were positively associated with alternative medicine usage
      for GERD.

PMID- 11837708
TI  - Does serum nitrite concentration reflect gastric carcinogenesis in Japanese
      Helicobacter pylori-infected patients?
AB  - This study investigated whether the serum nitrite concentration reflects
      Helicobacter pylori-induced inflammation and atrophic changes of gastric mucosa.
      Ninety-seven patients underwent biopsy of both antrum and fundus. Samples were
      analyzed by the rapid urease test and histopathological examination according to
      the updated Sydney system. Fasting serum samples from each subject were analyzed
      for specific IgG Helicobacter pylori antibodies, pepsinogen I and II
      concentrations, and NO2-/NO3- content. Eleven patients had H. pylori eradicated
      with proton pump-based triple therapy. There was a strong positive correlation
      between the Helicobacter pylori density in the gastric mucosa and the serum
      nitrite concentration, but a negative correlation existed between the atrophic
      grade of the gastric mucosa and both serum nitrite concentration and Helicobacter
      pylori density in the gastric mucosa. Serum nitrite concentrations decreased
      significantly after successful eradication of Helicobacter pylori. Therefore,
      serum nitrite concentration may be a useful marker for oxidative DNA damage and
      apoptosis associated with Helicobacter pylori infection.

PMID- 11837709
TI  - Helicobacter pylori infection and oncogene expressions in gastric carcinoma and
      its precursor lesions.
AB  - Although it is fairly well accepted that Helicobacter pylori infection plays a
      significant role in causing gastric cancer, the exact mechanisms involved in its
      pathogenesis are unclear. We have examined the relationship between H. pylori
      infection and oncogene expression in different stages of disease progression from
      precursor lesions to gastric carcinoma. We used Diff-Quik stain to diagnose H.
      pylori infection and immunohistochemical stains against c-erbB-2, p53, ras, c
      myc, and bcl-2 to determine expression of oncogenes. H. pylori infection was
      found in all cases of chronic gastritis, atrophic gastritis, intestinal
      metaplasia, and early gastric carcinoma, and in 16 of 30 (53%) cases of advanced
      gastric carcinoma. Overexpression of c-erbB-2 was found in 2 (7%) cases of
      advanced gastric carcinoma, which were H. pylori negative. Suppressor gene, p53,
      was overexpressed in 3 (30%) cases of intestinal metaplasia, 2 (33%) cases of
      early gastric carcinoma, and 18 (60%) cases of advanced gastric carcinoma. Of
      these 18 p53-positive advanced gastric cancer cases, 11 (61%) were H. pylori
      positive. Expression of ras p21 was found in 4 (40%) cases of H. pylori-negative
      normal mucosa, 10 (100%) cases of chronic gastritis, 1 (10%) case of atrophic
      mucosa, 6 (60%) cases of intestinal metaplasia, 2 (33%) cases of nonneoplastic
      mucosa adjacent to early gastric carcinoma, and 7 (23%) nonneoplastic mucosa
      adjacent to advanced gastric carcinoma, all of which showed H. pylori. No
      evidence of expression of either c-myc or bcl-2 was detected in any of the above
      mentioned samples. The data suggest that H. pylori infection may increase
      expression of ras p21 proteins and induce p53 suppressor gene mutation early in
      the process of gastric carcinogenesis.

PMID- 11837711
TI  - Metastatic malignant melanoma presenting as malabsorption.

PMID- 11837710
TI  - p53 mutation pattern and expression of c-erbB2 and c-met in gastric cancer:
      relation to histological subtypes, Helicobacter pylori infection, and prognosis.
AB  - The molecular mechanisms of Helicobacter pylori associated tumor development are
      poorly understood. The spectra of genetic alterations in neoplasms may provide
      clues to the molecular carcinogenesis of a tumor and may be relevant for the
      prognosis of the patients. We investigated the p53 mutation pattern and the
      protein expression of p53, c-erbB2, and c-met in 42 gastric cancers and
      correlated these alterations with H. pylori infection, histological subtypes and
      survival of the patients after curative resection. There were no differences in
      the incidences of the expression of p53, c-erbB2, and c-met in the tumor tissues
      according to H. pylori infection. Fifteen p53 mutations in 12 (29%) tumors were
      identified. More p53 mutations were found in patients with positive serology for
      H. pylori (43% vs 14%). This difference was not significant, but the small sample
      size may be insufficient to detect a potential statistical difference. There was
      neither a H. pylori-associated p53 hot-spot codon mutation nor a H. pylori
      characteristic mutational pattern of p53. Positive lymph nodes (P = 0.0061) and
      p53 mutations (P = 0.0035) were the only significant bad prognostic markers for
      survival after curative resection of the gastric cancers in our study. Our study
      does not indicate a unique molecular mechanism of p53 mutagenesis through H.
      pylori infection. The fact that p53 mutations were significantly correlated with
      poor survival of patients after potentially curative resection of gastric cancer
      may have clinical implications for multimodal therapies.

PMID- 11837712
TI  - A case of parathyroid hormone-related peptide producing gallbladder carcinoma and
      establishment of a cell line, PTHrP-GBK.

PMID- 11837713
TI  - Persistent multiple organ microcirculatory disorders in severe acute
      pancreatitis: experimental findings and clinical implications.
AB  - This study characterizes microcirculatory changes (capillary blood flow,
      capillary permeability, and leukocyte rolling) in the pancreas, colon, liver, and
      lungs at different stages of severe acute pancreatitis (AP) in a well-established
      rat model using intravital microscopy and computerized image analysis. The
      results demonstrate that microcirculatory disorders in severe AP are not confined
      to the pancreas but can also be found in the colon, liver, and lungs; that they
      extend beyond the early stage of AP and persist for 48 hr (and longer); and that
      they not only affect capillary blood flow but also involve prolonged changes of
      capillary permeability and leukocyte endothelial interaction. These findings may
      explain previous observations that therapeutic strategies aimed at enhancing
      microcirculation improve outcome in AP even if therapy is delayed and pancreatic
      necrosis can no longer be influenced. Since these systemic microcirculatory
      disturbances may contribute to AP-associated multiple organ dysfunction syndrome,
      further studies are warranted to evaluate whether improvement of microcirculation
      stabilizes organ function in AP and how long this may be effective after disease
      onset.

PMID- 11837714
TI  - Effect of carboxamide derivative IS-741 on rat spontaneous chronic pancreatitis.
AB  - This study aimed to analyze the therapeutic effects of the carboxamide derivative
      IS-741 on spontaneous chronic pancreatitis (CP) in the WBN/Kob rat. Four-week-old
      male WBN/Kob rats were fed with MB-3, and IS-741 (0.012% in MB-3) was orally
      administered for 12 weeks. Cytokine-induced neutrophil chemoattractant (CINC),
      interleukin (IL) -6, pancreatitis-associated protein (PAP), and p8 mRNAs in the
      pancreas were detected with semiquantitative reverse transcription-polymerase
      chain reaction (RT-PCR). Histological examination of the pancreas showed that
      hemorrhage, interstitial edema, and inflammatory cell infiltration were markedly
      less severe at 12 weeks, while fibrosis and acinar degeneration were also milder
      at 16 weeks, in the IS-741-treated rats than in untreated rats. The above
      mentioned genes were significantly suppressed in IS-741-treated rats at 12 weeks.
      Our results show that IS-741 exerts a potentially therapeutic effect on
      experimental CP by suppressing the expressions of the proinflammatory cytokines
      (IL-6 and CINC) and pancreatic acute phase proteins (PAP and p8).

PMID- 11837715
TI  - A rare manifestation of idiopathic hypereosinophilic syndrome: sclerosing
      cholangitis.

PMID- 11837716
TI  - Myenteric antiplexus antibodies and class II HLA in achalasia.
AB  - Achalasia, a motor disorder of the esophagus, is accompanied by autoimmune
      phenomena that could be playing a role in the pathogenesis of the disease. Our
      objective was to establish the genotypic frequency of the HLA-DR and DQ alleles
      in patients with achalasia and to establish their relationship with the presence
      of myenteric antiplexus antibodies in our geographic area. A total of 92 patients
      diagnosed with achalasia and two control groups with 275 healthy subjects were
      studied for HLA typing and 40 for autoantibodies determination. The myenteric
      antiplexus antibodies were positive in 50 patients (54.3%) and in 3 healthy
      subjects (7.5%) (P < 0.001). The patients showed a significantly higher frequency
      of DQA1*0103 and DQB1*0603 than was found in the controls. The heterodimer
      DQA1*0103-DQB1*0603 was increased in the patients [odds ratio (OR) = 2.57]. In
      regard to the association between the HLA DQA1 and DQB1 alleles and the
      antiplexus antibodies, these antibodies were found in greater prevalence in those
      patients with the DQA1*0103 and DQB1*0603 alleles, and the differences were
      statistically significant (OR = 3.17 and OR = 5.82, respectively). All of the
      women and 66.7% of the men with achalasia and the DQB1*0603 allele or the
      DQA1*0103-DQB1*0603 heterodimer were positive for antibodies.

PMID- 11837717
TI  - A synthetic prostaglandin E1 analog, alprostadil alfadex, relaxes sphincter of
      Oddi in humans.
AB  - It is well established that prostaglandins (PGs) exert potent pharmacological
      actions on vascular and nonvascular smooth muscle, although their effects on the
      sphincter of Oddi (SO) remain to be elucidated. The aim of this study was to
      investigate the effect of PGE1 on motility of the human SO. Twenty patients
      appearing for routine endoscopic retrograde cholangiopancreatography (ERCP)
      examination were studied. Each patient was randomly allocated to receive an
      intravenous infusion of normal saline (six patients), or alprostadil alfadex, a
      synthetic PGE1 analog, at a dose of either 0.05 or 0.1 microg/kg/min (seven
      patients for each condition). Endoscopic biliary manometry was done with a
      recording of basal SO pressure, amplitude of SO phasic contractions, and phasic
      contractile frequency before and 5 min after intravenous infusions, using a 4
      French microtransducer catheter. There was no significant change in SO motor
      variables following application of normal saline. Alprostadil alfadex
      significantly decreased basal SO pressure at a dose of 0.05 microg/kg/min, and
      significantly decreased all parameters at a dose of 0.1 microg/kg/min. A
      synthetic PGE1 analog, alprostadil alfadex, effectively inhibits motility of the
      human SO. This drug may be of clinical application as a SO-relaxing agent.

PMID- 11837718
TI  - Pirfenidone in the treatment of primary sclerosing cholangitis.
AB  - Our aim was to evaluate the safety and assess the efficacy of pirfenidone, an
      antifibrotic drug, in patients with primary sclerosing cholangitis (PSC). Twenty
      four patients with PSC were enrolled in this pilot study. Oral pirfenidone, 2400
      mg daily, was given for one year. Liver biochemistries were determined at three
      month intervals. The Mayo risk score was calculated, and liver biopsy and
      endoscopic cholangiography were performed at entry and at one year of treatment.
      No significant changes in liver biochemistries were noted at the end of the
      treatment period or at any of the three-month intervals. The Mayo risk score did
      not change significantly, and no significant changes were noted in the degree of
      inflammation, fibrosis, histologic stage of disease, or cholangiographic findings
      at the end of the treatment period. Adverse events occurred in 20/24 (83%)
      patients, but disappeared shortly after pirfenidone was discontinued. Pirfenidone
      did not benefit patients with PSC, and it was frequently associated with adverse
      events. The results of this pilot study discourage further trials of pirfenidone
      in patients with PSC.

PMID- 11837719
TI  - Atrophic corpus gastritis and Helicobacter pylori infection in primary biliary
      cirrhosis.
AB  - Chronic atrophic corpus gastritis, termed as autoimmune corpus gastritis or type
      A gastritis, and primary biliary cirrhosis (PBC) are characterized by a common
      immunological process against the exocrine glandular structures of both the
      stomach and bile duct. However, there has been controversy over whether atrophic
      corpus gastritis is associated with PBC. Recently, it has been suggested that
      Helicobacter pylori plays an important role in the early stage of atrophic corpus
      gastritis due to the induction of autoantibodies that are reactive with a protein
      in the gastric parietal cells. One hypothesis is that molecular mimicry, possibly
      resulting from H. pylori infection, might be responsible for initiating an
      autoimmune response in a predisposed host due to cross-reactivity among gastric
      mucosal, bile ductular, and bacterial antigens. The aim of this study is to
      assess whether atrophic changes of the gastric corpus could affect patients with
      PBC, and to determine the correlation with H. pylori infection. Sixteen patients
      with PBC were enrolled in this study. All patients were examined by serological
      studies of anti-pyruvate dehydrogenase (PDH) antibody, anti-H. pylori antibody,
      gastrin and vitamin B12. Gastroscopy was performed on all patients in order to
      verify the histological findings and to microscopically identify H. pylori.
      Atrophic corpus gastritis was found in 2 of 16 patients with PBC (12.5%), one of
      whom was confirmed to have pernicious anemia, a developed stage of atrophic
      corpus gastritis. H. pylori infection in the gastric corpus and the anti-H.
      pylori antibody were found in 7 (43.8%) and 11 (68.8%) of 16 patients,
      respectively. Anti-H. pylori antibody was confirmed to be positive in both of the
      patients with atrophic corpus gastritis, although H. pylori was absent in the
      gastric biopsy specimen. There was a positive correlation between anti-PDH
      antibodies and anti-H. pylori antibodies in sera from patients with PBC. Atrophic
      corpus gastritis is not frequently involved in PBC. However, H. pylori is a
      possible pathogenic factor in atrophic corpus gastritis in PBC patients because
      of the presence of anti-H. pylori antibody. A positive correlation between the
      titer of anti-PDH antibodies and the titer of anti-H. pylori antibodies was
      confirmed. Consequently, H. pylori infection could induce autoimmune responses in
      the development of both PBC and atrophic corpus gastritis. H. pylori infection
      associated with PBC requires further study.

PMID- 11837721
TI  - Efficacy of early immunosuppressive therapy in a child with carbamazepine
      associated vanishing bile duct and Stevens-Johnson syndromes.

PMID- 11837720
TI  - Interferon inhibits progression of liver fibrosis and reduces the risk of
      hepatocarcinogenesis in patients with chronic hepatitis C: a retrospective
      multicenter analysis of 652 patients.
AB  - A retrospective multicenter analysis of 652 patients with chronic hepatitis C who
      have been treated with interferon (IFN) was performed to assess the effects of
      IFN on the clinical course and development of HCC. During a mean follow-up of
      54.8 months, hepatocellular carcinoma (HCC) developed in 7.0% of the patients.
      The rate was significantly higher in the patients who did not respond to IFN
      treatment than in those with sustained virological response and those who
      obtained a normalization of alanine aminotransferase levels despite the presence
      of HCV RNA (incomplete response) (P < 0.01). Using multivariate Cox's
      proportional hazard model, alcohol abuse (P < 0.05) and a higher level of
      fibrosis (P < 0.05) before treatment were the significant background factors
      associated with HCC development in the patients who did not respond to IFN.
      Interestingly, a significant increase in the rate of HCC development occurred in
      patients who had a histological finding of progressive fibrosis (F3). In
      addition, patients with low histological staging scores were likely to have an
      incomplete response, even if a sustained virological response was not obtained.
      IFN produced an improvement in histological activity and fibrosis stage in the
      second biopsy specimens irrespective of the clinical outcome when compared
      against untreated subjects.

PMID- 11837722
TI  - Alterations in serum leptin in chronic liver disease.
AB  - The role of leptin in anorexia associated with liver cirrhosis remains
      controversial. The aim of this study was to quantify the serum leptin level in
      patients with hepatocellular or cholestatic liver disease and to assess its
      relationship with serum insulin, body mass index, and serum lipoproteins. The
      study population included 30 women, 15 with chronic hepatocellular liver disease
      and 15 with primary biliary cirrhosis; severity of disease was determined by
      Child-Pugh and histological criteria, respectively. Ten healthy, age-matched
      women served as controls. Levels of serum leptin and insulin were determined by
      radioimmunoassay. Mean serum leptin level was significantly lower in the primary
      biliary cirrhosis group compared to both the control (P < or = 0.05) and the
      hepatocellular groups (P < or = 0.05). Serum leptin level strongly correlated
      with body mass index in the hepatocellular group (P < 0.0001) and the controls (P
      < 0.001), but not in the primary biliary cirrhosis group; it showed no
      correlation with severity of liver disease. A positive correlation was found
      between serum leptin and serum cholesterol (P = 0.02), low density lipoprotein (P
      = 0.01), and triglycerides (P = 0.04) in the hepatocellular group and in the
      controls between serum leptin and serum high density lipoproteins (P = 0.01).
      Serum leptin is low in patients with primary biliary cirrhosis. The combined
      findings of normal insulin response less insulin resistance, and lower serum
      leptin level in primary biliary cirrhosis compared to hepatocellular liver
      disease may indicate that serum leptin is merely a passive marker and not a cause
      of anorexia in liver disease.

PMID- 11837723
TI  - Ileal luminal nitric oxide synthase inhibitors and E. coli lipopolysaccharide
      effects in the anesthetized rat.
AB  - Some of the effects of bacterial toxins are mediated through the local production
      of nitric oxide (NO) or its products. This study examined if NO inhibition in the
      intestinal mucosa had effects on the responses to intravenous lipopolysaccharide
      (LPS) in anesthetized rats. Aminoguanidine (AMGU, 500 microM), a relatively
      selective inducible NO synthase (iNOS) inhibitor, or N(G)-nitro-L-arginine
      (NOLARG, 50 or 500 microM), a nonselective inhibitor of iNOS and constitutive NOS
      (cNOS), were perfused through the ileal lumen during intravenous LPS (17 mg/kg)
      or saline administration. Intestinal H20 transport, NO3- + NO2- (NOx) secretion,
      absorptive site mucosal blood flow (ASBF), blood pressure, plasma [NOx], tissue
      damage, and blood leukocytes were measured for 4 hr. LPS increased luminal NOx
      secretion. At 50 microM, luminal NOLARG attenuated the LPS-induced NOx secretion
      and increased blood pressure. There were no significant changes in lethality,
      plasma [NOx] or other parameters. At 500 microM, luminal NOLARG converted a
      nonlethal dose of LPS into a lethal dose, but AMGU did not increase lethality.
      The LPS-induced luminal NOx secretion was blocked by 500 microM intraluminal AMGU
      and NOLARG. Luminal NOx secretion also increased in control animals. This
      increase was blocked by 500 microM NOLARG but not AMGU. Luminal 500 microM NOLARG
      increased blood pressure, but AMGU did not. Luminal 500 microM NOLARG prevented
      the LPS-induced increase in plasma [NOx] and the decrease in leukocytes, but AMGU
      did not. Tissue damage occurred with intravenous LPS plus intraluminal 500 microM
      NOLARG. It was concluded that luminal AMGU inhibited mucosal iNOS. Luminal NOLARG
      inhibited mucosal cNOS and iNOS, and cNOS inhibition primed a lethal LPS effect.
      NOLARG, but not AMGU, was absorbed from the intestine and had systemic effects.

PMID- 11837724
TI  - Quality of life in functional dyspepsia.
AB  - Our purpose was to assess the quality of life of functional dyspepsia patients
      using the SF-36 generic scale and the Gastrointestinal Symptoms Rating Scale
      (GSRS). In all, 328 dyspeptic patients were included in a multicenter,
      prospective, observational study. Both scales were filled out at baseline and one
      and three months after a prokinetic agent was given as a single-drug therapy. A
      total of 250 patients completed the study. An improvement in all SF-36 dimensions
      was observed, although the final scores were lower than the population reference
      values. Physical role (27% change), emotional role (20%), and physical pain (16%)
      dimensions showed the greater change. The GSRS total and domain scores also
      showed significant decreases. The best predictors of quality of life improvement
      were certain basal symptoms, drug compliance, and the absence of idiopathic
      dyspepsia. In conclusion, both the generic and the specific scales provide useful
      and sensitive measures of quality of life in functional dyspepsia patients on
      single-drug treatment.

PMID- 11837725
TI  - Epidemiology of Clostridium difficile infection in a large population of
      hospitalized US military veterans.
AB  - The Patient Treatment File (PTF) of the Department of Veterans Affairs (VA)
      comprises the computerized records of all inpatients treated at all VA hospitals
      throughout the United States. The database was utilized to study the clinical
      epidemiology and impact of C. difficile colitis on health care among hospitalized
      US military veterans. The computerized medical records of 15,091 cases with C.
      difficile colitis and 61,931 controls without the diagnosis were extracted from
      the annual files between 1993 and 1998. Of all patients admitted to the hospital,
      1% were diagnosed with C. difficile colitis, in 16% of whom it was listed as the
      primary discharge diagnosis. C. difficile colitis was more likely to occur in
      elderly white patients with multiple comorbid conditions. Compared with a control
      population of hospitalized patients without C. difficile colitis, the case
      population was subjected to more medical and surgical procedures and experienced
      longer hospital stays. The diagnosis of C. difficile colitis was associated with
      more frequent admissions to the intensive care unit and higher hospital-related
      and subsequent mortality. Eleven percent of the cases were admitted to hospital a
      second time after a mean of 202 days, 2.5% were readmitted a third time after an
      additional 182 days, and 0.8% were readmitted a fourth time after an additional
      194 days. In conclusion, as old age, multiple comorbid conditions, a high number
      of medical and surgical intervention, and long hospitalization constitute the
      main risk factors for the development of C. difficile colitis, efforts at
      prevention should be directed primarily towards patients who present with these
      characteristics.

PMID- 11837726
TI  - Impaired synthesis or cellular storage of norepinephrine, dopamine, and 5
      hydroxytryptamine in human inflammatory bowel disease.
AB  - The present study was aimed at evaluating the extent of dysfunction of the
      enteroendocrine and enteric nervous system, as indicated by changes in tissue
      levels of monoamines (dopamine, DA; norepinephrine, NE; 5-hydroxytryptamine, 5
      HT) and their precursors and metabolites in the colonic mucosa of patients
      afflicted with ulcerative colitis (UC, N = 21) and Crohn's disease (CD, N = 22).
      In CD, but not in UC, NE tissue levels in both the noninflamed and inflamed
      colonic mucosa were markedly lower than in control subjects (N = 16). In the
      inflamed mucosa of CD and in UC patients levels of L-DOPA were twice those in
      controls. DA levels in the inflamed mucosa of CD and UC patients were markedly
      lower than in controls. This resulted in significant reductions in DA/L-DOPA
      tissue ratios, a rough measure of L-amino acid decarboxylase activity. 5-HT
      levels in the inflamed mucosa of CD and UC patients were markedly lower than in
      controls. In conclusion, intestinal cellular structures responsible for the
      synthesis and storage of DA, NE, and 5-HT may have been affected by the
      associated inflammatory process in both CD and UC.

PMID- 11837727
TI  - Functional gastrointestinal disorders in Canada: first population-based survey
      using Rome II criteria with suggestions for improving the questionnaire.
AB  - The Rome II criteria and questionnaires developed to identify functional
      gastrointestinal disorders have not been evaluated. Our objectives were to
      determine the prevalence of functional gastrointestinal disorders in Canada,
      compare our results with data from other published studies, assess concordance of
      Rome I and Rome II criteria for irritable bowel syndrome, and suggest
      improvements in the Rome II questionnaire. An independent research firm was
      employed to conduct a random digit dial national survey, inviting household
      members > or = 18 years of age to participate in a study examining personal
      health issues. Subjects recruited by telephone, who agreed to participate, were
      mailed a questionnaire, and the data were retrieved by a follow-up phone call.
      The Rome II questionnaire and algorithms were used and where possible Rome I
      algorithms were also applied. At least one functional gastrointestinal disorder
      occurred in 61.7% of 1149 respondents (65.6% female versus 57.6% male; P < 0.05).
      The most prevalent were the functional bowel disorders at 41.6% followed by
      esophageal disorders at 28.9%. Irritable bowel syndrome prevalence by Rome II and
      I criteria were 12.1% and 13.5%, respectively (kappa = 0.76). Because the Rome II
      criteria have added exclusion items that are not present in the Rome I criteria,
      the prevalence of esophageal, gastroduodenal, and anorectal disorders is lower
      than the figures from a US market survey. In conclusion, functional
      gastrointestinal disorders are highly prevalent in Canada, with a significantly
      higher rate in women. There is substantial agreement between Rome I and Rome II
      criteria for irritable bowel syndrome. Rome criteria and questionnaire remain
      works in progress.

PMID- 11837728
TI  - Physician perception of IBS management in women and men.
AB  - Irritable bowel syndrome is a common gastrointestinal disorder that is manifested
      by abdominal pain and an alteration in bowel habits. It is estimated to occur in
      approximately 20% of the US population and is diagnosed more frequently in women
      compared to men. The principles of management do not differ based upon gender.
      However, there is not data that has evaluated physician perception of IBS
      diagnosis and management. This study evaluated internal medicine physicians'
      perception of IBS in women and men. Sixty internal medicine physicians (30 men,
      30 women) completed anonymous surveys evaluating their perception of the ease of
      diagnosis and management of IBS. A database was created and analyzed using Epi
      Info. Statistical significance was determined with chi-square tables that
      generated P values. IBS was more frequently diagnosed in women. There was a
      statistically significant difference in women with IBS being not easy to diagnose
      when compared to men with IBS (P = 0.0003). There was also a statistically
      significant difference in men with IBS being reported to be not easy to manage
      when compared to women with IBS (P = 0.0014). This study revealed that physicians
      perceive a difference in the ease of diagnosis and management of IBS based upon
      gender. Further research is necessary to gain insight into the influence of
      patient gender upon this disorder.

PMID- 11837729
TI  - Autonomic function in patients with functional dyspepsia assessed by 24-hour
      heart rate variability.
AB  - The function of the autonomic nervous system was assessed in 23 patients with
      dysmotility-like functional dyspepsia and 12 healthy volunteers by analysis of 24
      hr heart rate variability and a battery of five standardized sympathetic and
      parasympathetic cardiovascular reflex tests. Measures of heart rate variability
      were obtained by analysis of ambulatory electrocardiographic recordings using
      both the time and the frequency domain methods. The values of parameters
      reflecting vagal activity (HF, rMSSD) were significantly lower in patients with
      functional dyspepsia. Individual analysis of heart rate variability data
      identified at least one abnormal parameter of vagal function in seven (30.4%)
      patients, and in five of these the results of parasympathetic cardiovascular
      reflex tests were also abnormal. Our results suggest impaired efferent vagal
      function in a subgroup of patients with functional dyspepsia. This abnormality
      may play a role in the pathogenesis of the disease in these patients.

PMID- 11837730
TI  - Nutritional implications of chronic dyspepsia in childhood.
AB  - Chronic dyspepsia is common in children. However, the association of individual
      predominant symptoms with gastric emptying and their impact on nutritional status
      are poorly defined. We therefore studied 31 children (mean age 11 years, 14 boys)
      with chronic dyspepsia and classified their predominant symptoms (PS) by their
      character and severity. Gastric emptying (GE) T(1/2) of a solid meal was carried
      out in all patients, while upper gastrointestinal endoscopy was done in the
      treatment failures. All patients received two months treatment with cisapride.
      Weight for age z scores were recorded before and three months after treatment.
      There were 12 patients with epigastric pain (EP) as the PS (7 moderate/severe).
      Postprandial fullness (PF) was the PS in 19 patients (12 moderate/severe). GE
      T(1/2) was prolonged and weight for age z scores were lower in children who had
      moderate/severe (but not mild) PF comparing to those who had EP (P < 0.0001 and P
      = 0.003, respectively). A significant improvement in weight was observed in the
      same group alone following treatment with cisapride (P = 0.0003). In conclusion,
      impaired GE is common in dyspeptic children with PF and have adverse effects on
      nutritional status.

PMID- 11837732
TI  - Decrease of intragastric acidity in healthy subjects dosed with ranitidine 75 mg,
      cimetidine 200 mg, or placebo.
AB  - This study assessed the duration of action of single doses of ranitidine (75 mg),
      cimetidine (200 mg), or placebo on intragastric acidity in healthy subjects. When
      dosed with placebo, mean daytime intragastric acidity (0-10 hr after dose) was
      37.62 mmol/liter, decreasing to 17.21 mmol/liter (mean decrease 59%; P < 0.001 vs
      placebo) and 25.06 mmol/liter (mean decrease 35%; P < 0.001 vs placebo) when
      treated with ranitidine and cimetidine, respectively. Ranitidine inhibited
      intragastric acidity to a greater degree than cimetidine (P < 0.001). Mean
      nighttime (10-20 hr after-dose) intragastric acidity when dosed with placebo was
      34.37 mmol/liter, decreasing to 29.06 mmol/liter (mean decrease 18%; P = 0.027 vs
      placebo) when dosed with ranitidine and remaining virtually unchanged at 33.85
      mmol/liter (mean decrease 2%; NS vs. placebo) when dosed with cimetidine.
      Ranitidine inhibited acidity to a greater degree than cimetidine (P = 0.043). The
      inhibitory effect of ranitidine, 75 mg, on intragastric acidity can be detected
      from 0-15 hr after an oral dose. Cimetidine 200 mg has little inhibitory effect
      beyond 10 hr.

PMID- 11837731
TI  - Mechanisms involved in protection afforded by L-arginine in ibuprofen-induced
      gastric damage: role of nitric oxide and prostaglandins.
AB  - L-Arginine (L-arg) exhibits multiple biological properties and plays an important
      role in the regulation of different functions in pathological conditions. Many of
      these effects could be achieved on this amino acid serving as a substrate for the
      enzyme nitric oxide synthase (NOS). At the gastrointestinal level, recent reports
      revealed its protective activities involving a hyperemic response increasing the
      gastric blood flow. The aim of this study was to characterize the relationship
      between NOS activity/expression and prostaglandin changes (PGs) in rats gastric
      mucosa, with L-arg associated resistance to the nonsteroidal anti-inflammatory
      drug (NSAID) ibuprofen (IBP). The protective effect of oral L-arg (100 mg/kg body
      wt), administerred together with IBP (100 mg/kg body wt, per os), was evident
      enough 90 min after drug administration, although a significant protection
      persisted for more than 6 hr. Pretreatment with N(G)-nitro-L-arginine (L-NNA) (40
      mg/kg body wt, intraperitoneally), a competitive inhibitor of constitutive NOS,
      partly altered the protection afforded by the amino acid. In contrast, no changes
      could be observed after inducible NOS inhibition [aminoguanidine (AG) 50 mg/Kg
      body wt, intraperitoneally). L-arg, plus IBP, produced a significant increase of
      the cyclic GMP (cGMP) response in tissue samples from rat stomach, 90 min and 6 h
      after drug administration. iNOS activity and mRNA expression were higher in IBP
      treated rats, and no differences were observed in inducible responses in the L
      arg plus IBP group. No variations in the cNOS activity and expression were found
      among the different groups of animals assayed. The measurement of mucosal PGE2
      content confirmed that biosynthesis of the eicosanoid is maintained by L-arg for
      over 90 min after IBP, while a total inhibition was observed 6 hr later. The
      mechanisms of the L-arg protective effect on the damaged induced by IBP could be
      explained by the different period after drug administration. The early phase is
      mediated by cyclooxygenase/prostaglandins pathway (COX/PGs) although NO liberated
      by cNOS and the guanylate cyclase/cGMP pathway could be also relevant. The later
      phase implicates inhibition of the iNOS/NO response.

PMID- 11837733
TI  - Gastrointestinal involvement in paroxysmal nocturnal hemoglobinuria: first report
      of electron microscopic findings.
AB  - Thrombotic complications, particularly microthrombi involving intraabdominal
      veins leading to intestinal ischemia, have remained a major cause of morbidity in
      patients with paroxysmal nocturnal hemoglobinuria (PNH). While intestinal
      ischemia has been postulated to be the cause of recurrent bouts of abdominal pain
      in this population, direct antemortem evidence for this complication is scarcely
      documented in the literature. We describe a case of PNH in a patient who
      presented with abdominal distress three years after the initial diagnosis was
      established. Clinical features and a combination of diagnostic modalities,
      including radiography, endoscopy, and histology were used to make the prompt
      diagnosis of intestinal ischemia. This is the first case in which the electronic
      microscopy of the gastrointestinal lesion is described. Our patient was
      successfully treated with conservative measures and anticoagulation.

PMID- 11837734
TI  - Significance of blood urea: gastric ammonia gradient for H. pylori detection in
      childhood.

PMID- 11837736
TI  - Randomized trial assessing gastric emptying in patients with chronic hepatitis C
      during interferon-alpha or -beta therapy and effect of cisapride.
AB  - We examined the effects of interferon-alpha or -beta therapy on gastric emptying
      and digestive symptoms. The effects of cisapride on gastric emptying and
      digestive symptoms were also evaluated. The subjects were 48 patients with
      chronic hepatitis C. All patients were randomly assigned to one of four groups
      (A, interferon-alpha group; B, interferon-alpha and cisapride group; C,
      interferon-beta group; D, interferon-beta and cisapride group). Gastric emptying
      was measured before initiation of interferon therapy and two weeks after
      initiation of therapy. The half-time of gastric emptying (T1/2) was calculated.
      The T1/2 ratio was calculated by dividing the T1/2 after interferon therapy by
      the T1/2 before interferon therapy. Digestive symptom scores were determined at
      the time of the gastric emptying tests. The T1/2 after interferon therapy was
      higher than that before therapy in groups A and C (P = 0.002 and 0.059,
      respectively). The digestive symptom score after interferon therapy was higher
      than that before therapy in groups A and C (P = 0.012 and 0.093, respectively).
      The T1/2 ratio in group B was significantly lower than that in group A (P =
      0.021), and the T1/2 ratio in group D was lower than that in group C, but the
      difference did not reach statistical significance (P = 0.057). Interferon-alpha
      is associated with a greater delay in gastric emptying and a higher symptom score
      than is interferon-beta. Administration of cisapride corrects the delayed gastric
      emptying and relieves associated digestive symptoms.

PMID- 11837735
TI  - Hyperglycemia attenuates erythromycin-induced acceleration of liquid-phase
      gastric emptying of hypertonic liquids in healthy subjects.
AB  - Acute hyperglycemia has been associated with delayed gastric emptying in healthy
      controls. Erythromycin has recently been found to be a gastrointestinal
      prokinetic agent in both solids and hypertonic liquids. Our aim was to examine
      whether the acute steady-state hyperglycemia reduces the erythromycin-induced
      acceleration of gastric emptying of hypertonic liquids after a fasted state of
      the stomach in healthy subjects. In 12 healthy subjects scintigraphic measurement
      of gastric emptying of a hypertonic radiolabeled liquid meal, during
      normoglycemia (5-8.9 mmol/l glucose) or induced hyperglycemia (16-19 mmol/liter
      glucose) by intravenous glucose infusion after giving either placebo or 200 mg
      intravenous erythromycin, was performed on four separate days in random order. In
      the hyperglycemic state compared with normoglycemia, either after placebo
      administration or erythromycin, the gastric emptying of the hypertonic liquid was
      reduced. The lag-phase duration was significantly increased (17.5 +/- 5.5 min,
      and 7.2 +/- 4.5 min vs 10.5 +/- 3.4 min, and 3.5 +/- 2.5 min, respectively, P <
      0.0001) as were the overall T1/2 (gastric emptying time of the half meal) (52.5
      +/- 13 min and 24.5 +/- 5.5 min vs 42 +/- 10.5 min, and 16 +/- 6 min,
      respectively, P < 0.0001) and the percentage of liquid meal retained in the
      stomach at 60 and 100 min postprandially (P < 0.001). In conclusion,
      hyperglycaemia attenuates the acceleration effect of erythromycin and decreases
      the overall gastric emptying rate of hypertonic liquids in healthy subjects.

PMID- 11837737
TI  - Endoscopy in patients receiving radiation therapy to the thorax.
AB  - Radiation therapy for thoracic malignancies is often complicated by radiation
      induced esophagitis. Symptoms of radiation esophagitis are nonspecific and
      include dysphagia, odynophagia, and chest pain. Patients receiving radiation
      therapy are also at risk for infectious esophagitis, which can be indistinguished
      clinically from radiation-induced esophagitis. We retrospectively reviewed data
      on patients who had esophagitis symptoms during or after thoracic radiation
      therapy and were referred for upper endoscopy. We sought to determine how often
      infectious esophagitis or cancer was present, as compared to radiation-induced
      esophagitis alone. Twenty-four upper endoscopies were performed on 16 patients
      over a three-year period to evaluate esophagitis symptoms. Forty-four percent of
      the patients endoscoped had infectious esophagitis or recurrent cancer diagnosed
      by endoscopy. No complications occurred from the procedures. Esophagoscopy is a
      safe procedure that should be considered, to exclude infection or cancer, in
      patients who develop esophagitis symptoms during or after thoracic radiation.

PMID- 11837738
TI  - Effects of prostaglandins on spontaneous apoptosis in gastric mucosal cells.
AB  - Prostaglandins have cytoprotective effects on gastric mucosa via the influence of
      various mechanisms. The purpose of this study is to examine the effects of
      prostaglandins on maturation-dependent spontaneous apoptosis in gastric mucosal
      cells in vitro, which mimics the apoptosis of gastric mucosal cells related with
      a rapid cell turnover rate in vivo. Both prostaglandin E1 and E2 inhibited
      spontaneous apoptosis in a dose-dependent manner and increased the viability of
      gastric mucosal cells in culture. A number of antiulcer drugs presently in
      clinical use were shown to increase the concentrations of prostaglandins in
      cells. All of the drugs tested clearly inhibited the spontaneous apoptosis in a
      dose-dependent manner. Based on these results, we propose that the cytoprotective
      effects of prostaglandins on gastric mucosa in vivo can be partially explained by
      an increase in the number of gastric mucosal cells present as a result of the
      inhibition of maturation-dependent spontaneous apoptosis.

PMID- 11837739
TI  - Symptom predictability of reflux-induced respiratory disease.
AB  - Gastroesophageal reflux disease (GERD) often is associated with pulmonary
      problems such as asthma as well as recurrent and nocturnal cough. Dual-probe 24
      hr pH monitoring may assist in establishing a correlation between these symptoms
      and GERD-related symptoms. To determine if any specific symptom was predictive of
      aspiration, this study was undertaken. Ambulatory dual-probe esophageal pH
      monitoring was performed on 133 patients who had upper airway and additional
      symptoms for GERD. All patients had esophageal manometric studies of the lower
      esophageal sphincter (LES), the upper esophageal sphincter (UES), and the
      esophageal body before dual-probe pH monitoring was performed. Using two
      assembled glass probes, the distal and the proximal sensors were placed 5 cm
      above the proximal border of the LES and 1 cm below the lower border of the UES,
      respectively. Patients were classified into three groups: proximal and distal
      probe positive (group I), proximal probe negative and distal probe positive
      (group II) and proximal and distal probe negative (Group III) Upper airway and
      additional symptoms plus manometry results of the LES, body and UES study were
      compared between groups. In addition, positive distal probe patients (groups I
      and II) were compared for distal fraction of time at pH < 4 and number of reflux
      episodes at each probe position. A positive distal probe result was defined as an
      abnormal DeMeester score (> 14.8). A proximal probe test result was considered
      positive if percent time pH < 4.0 was > 1.1 for total, 1.7 for upright, and 0.6
      for supine positions. The ages of the subjects ranged from 18 to 83 years (mean
      age: 50.5 +/- 1.5 years). Groups I, II, and III included 16 patients, 38
      patients, and 79 patients, respectively. Group I had a significantly higher
      incidence of nocturnal cough than the other two groups. (P < 0.05). The
      manometric data revealed between groups that LES pressure (LESP) for groups I and
      II was significantly lower than LESP for group III (P = 0.003). Cricoid pressure,
      pharyngeal pressure, length, and relaxation of UES were not different between
      groups. Fraction of reflux time for group I was significantly higher than for
      group II in the supine position and at mealtime (P < 0.05). The number of reflux
      episodes for group I was significantly higher at meal time (P < 0.01). In
      conclusion, nocturnal cough is strongly predictive of proximal esophageal reflux.
      Proximal reflux episodes are significantly more frequent in the supine position
      and correlate well with the high predictive value of nocturnal cough.

PMID- 11837740
TI  - Attenuated apoptosis in H. pylori-colonized gastric mucosa of Mongolian gerbils
      in comparison with mice.
AB  - Although gastric cancer formation with H. pylori in Mongolian gerbils was
      recently reported, the same inoculation procedure did not result in cancer
      formation in other animals such as mice. Disturbed regulation of apoptosis and
      cell proliferation are known to link the multistep process of carcinogenesis. The
      present study is designed to examine the level of gastric epithelial cell
      apoptosis in Mongolian gerbils colonized with the H. pylori (Sydney strain: SS1)
      in comparison with that in mice. Mice (C57BL/6) and Mongolian gerbils were orally
      inoculated with SS1 and the stomachs were examined 9 and 18 months later. MPO
      activity increased persistently in gerbils, but increased transiently in mice.
      While the levels of DNA fragmentation, caspase-3 activity, and the number of
      TUNEL-positive cells increased significantly in mice, such parameters were
      attenuated in gerbils. On the other hand, the number of PCNA-positive cells
      increased after SS1 inoculation only in Mongolian gerbils, suggesting the
      enhancement of cell turnover in H. pylori-colonized gerbils. In conclusion, the
      SS1-induced increase in gastric mucosal apoptosis observed in mice was attenuated
      significantly in Mongolian gerbils, suggesting the causative role for the higher
      incidence of gastric carcinogenesis in this animal.

PMID- 11837741
TI  - Evaluation of proliferative index and cell cycle protein expression in choroid
      plexus tumors in children.
AB  - Choroid plexus tumors are papillary neoplasms originating from the epithelium of
      the choroid plexus within the cerebral ventricles. They may be highly
      proliferative tumors, but detailed studies confirming their proliferative
      potential are lacking. Accordingly, we performed a clinicopathological
      correlation study of neoplasms arising from the choroid plexus in children using
      immunohistochemistry to characterize both their proliferative potential and their
      degree of cell cycle dysregulation when compared to non-neoplastic choroid
      epithelium. Twelve children with choroid plexus papillomas (CPPs) and 11 with
      choroid plexus carcinomas (CPCs) were identified from the time period 1982-1997.
      The outcome and survival of these children following treatment was determined
      from the medical record. Immunohistochemical studies were performed on CPPs and
      CPCs in this patient population and on non-neoplastic choroid epithelium using
      antibodies to MIB-1, p53, cyclin E, retinoblastoma protein (pRB), p107, and E2F
      1. In 5 children with CPCs, tumor tissue was available for immunohistochemistry
      at a second surgery after cycles of chemotherapy had been given. The mean
      survival for patients with CPPs was 8.5 years, and with CPCs 5.2 years with a
      minimum follow-up of 4 years for the group. The expression of cell cycle markers
      and MIB-1 was greater in CPCs than in CPPs or normal choroid plexus. The
      expression of MIB-1, p53, pRB, and E2F-1 was significantly lower in patients with
      CPCs after chemotherapy than before. The MIB-1 labeling index for CPC patients
      who are alive and well after treatments was 15.19+/-3.2 compared to 22.63+/-3.04
      for patients who have died from their disease (P<0.05). We conclude that CPCs in
      children are characterized by a higher MIB-1 labeling index and greater cell
      cycle dysregulation than are CPPs. Chemotherapy may work in part on CPCs to
      decrease their proliferative potential and expression of cell cycle regulatory
      proteins.

PMID- 11837742
TI  - Demyelination precedes oligodendrocyte loss in canine distemper virus-induced
      encephalitis.
AB  - Canine distemper virus (CDV), a negative-stranded RNA morbillivirus, causes a
      persistent infection within the central nervous system resulting in a
      progressive, multifocal demyelinating disease. Demyelination is thought to be
      caused by a selective alteration of the myelin-producing oligodendrocytes.
      Metabolic impairment and morphological changes of the oligodendrocytes after CDV
      infection have previously been observed in vitro as well as in vivo. Until now it
      has been suggested that the oligodendrocytes completely disappear from CDV
      induced demyelinating lesions. However, ultrastructural analysis in brain tissue
      sections and immunohistochemical examination of oligodendrocytes in dog brain
      cell cultures contradicted these observations. In this study oligodendrocytes
      from different categories of CDV-induced lesions were examined by in situ
      hybridization for proteolipid protein mRNA and--as a new tool employed on canine
      brain tissue sections--by immunohistochemistry using a monoclonal antibody
      against 2',3'-cyclic nucleotide 3'-phosphodiesterase, a myelin-specific enzyme. A
      down-regulation in the myelin gene transcription was detected already before
      demyelination occurred. However, a decrease in the number of oligodendrocytes was
      not observed until demyelination became evident. Although there was further
      depletion of oligodendrocytes in plaques with progressive demyelination, we
      demonstrated for the first time that these cells were still present in a
      significant amount even in chronic, completely demyelinated distemper lesions.

PMID- 11837743
TI  - Expression of 8-oxoguanine DNA glycosylase is reduced and associated with
      neurofibrillary tangles in Alzheimer's disease brain.
AB  - Recent studies have confirmed the role of reactive oxygen species in the
      pathogenesis of Alzheimer's disease (AD). 8-Oxo-2'-deoxyguanosine accumulation in
      AD brain has been discussed, but few studies of DNA repair enzymes in AD brain
      have been done. Further, a relationship between mitochondrial function and
      oxidative stress has been noticed. In this study, to evaluate the repair
      mechanism for oxidative DNA damage in AD brain, we investigated brain tissues
      from autopsy cases of AD and control cases using an antibody against the
      mitochondrial form of 8-oxoguanine DNA glycosylase (hOGG1-2a), an enzyme that
      repairs 8-oxo-2'-deoxyguanosine. hOGGI-2a is expressed mainly in the neuronal
      cytoplasm in both AD and control cases in regionally different manners.
      Expression of hOGG1-2a is decreased in the orbitofrontal gyrus and entorhinal
      cortex in AD compared to that in control cases. Immunoreactivity to hOGG1-2a is
      associated with neurofibrillary tangles, dystrophic neurites and reactive
      astrocytes in AD. Our results indicate that the repair enzyme for oxidative
      damage in mitochondrial DNA may not function appropriately in AD, and thus
      oxidative DNA damage in mitochondria may be involved in the pathomechanism of AD.

PMID- 11837744
TI  - Specific tau phosphorylation sites correlate with severity of neuronal
      cytopathology in Alzheimer's disease.
AB  - Microtubule associated protein tau is abnormally phosphorylated in Alzheimer's
      disease (AD) and aggregates as paired helical filaments (PHFs) in neurofibrillary
      tangles (NFTs). We show here that the pattern of tau phosphorylation correlates
      with the loss of neuronal integrity. Studies using 11 phosphorylation dependent
      tau antibodies and a panel of AD cases of varying severity were evaluated in
      terms of three stages of neurofibrillary tangle development: (1) pre
      neurofibrillary tangle, (2) intra-, and (3) extra-neuronal neurofibrillary
      tangles. The pretangle state, in which neurons display nonfibrillar, punctate
      regions in the cytoplasm, sound dendrites, somas, and nuclei, was observed
      especially with phospho-tau antibodies TG3 (pT231), pS262, and pT153.
      Intraneuronal neurofibrillary tangles are homogenously stained with fibrillar tau
      structures, which were most prominently stained with pT175/181, 12E8
      (pS262/pS356), pS422, pS46, pS214 antibodies. Extracellular NFTs, which contain
      substantial filamentous tau, are most prominently stained with AT8
      (pS199/pS202/pT205), AT100 (pT212/pS214), and PHF-1 (pS396/pS404) antibodies,
      which also stain intracellular NFT. The sequence of early tau phosphorylation
      suggests that there are events prior to filament formation that are specific to
      particular phosphorylated tau epitopes, leading to conformational changes and
      cytopathological alterations.

PMID- 11837745
TI  - Traumatic compaction of the axonal cytoskeleton induces argyrophilia:
      histological and theoretical importance.
AB  - It was earlier established that one of the primary morphopathological
      consequences of experimental traumatic brain injury is a dramatic reduction in
      the distances between the neurofilaments (cytoskeletal compaction) inside a
      number of axon segments that appear to be randomly distributed among normal axons
      in an otherwise undamaged parenchymal environment. The present results
      demonstrate that the cytoskeletal compaction instantly induces argyrophilia,
      thereby rendering possible selective visualisation of the affected axon segments
      for light microscopy through use of a special silver staining method. On
      combination of this method with electron microscopy, it was revealed that the
      cytoskeletal compaction is completed in much shorter times and extends to much
      longer axon segments than previously assumed.

PMID- 11837746
TI  - Unbiased morphological measurements show no neuronal loss in the substantia nigra
      in Alzheimer's disease.
AB  - This is the first study to use the unbiased stereological method, the disector,
      to estimate the total number of pigmented neurons in the pars compacta of the
      substantia nigra (SNpc) in Alzheimer's disease (AD) patients as compared to
      healthy controls. The right half of the SNpc of 11 AD patients and 24 controls
      was studied. We also used single sections to determine the neuronal number and
      area in different subregions of the SNpc. The results showed that there was no
      significant difference in the total number of pigmented neurons in the SNpc
      (154,415+/-13,593 for AD and 160,163+/-8027 for controls) or in the volume of the
      SNpc between the patients with AD and controls. Studies on single sections
      revealed that even subregionally there was no significant difference in the
      neuronal number or area in the SNpc between AD patients and controls.

PMID- 11837747
TI  - Amyloid-beta deposits in the cerebral cortex of the aged common marmoset
      (Callithrix jacchus): incidence and chemical composition.
AB  - The incidence, distribution and chemical composition of amyloid-beta (A beta)
      peptide-positive deposits were investigated in the lower primate species common
      marmoset (Callithrix jacchus). No A beta deposits were observed in the brains of
      7 marmosets below 7 years of age. In 15 marmosets above 7 years, 60% displayed
      cortical A beta-immunoreactive plaques, 80% had A beta deposited in intracortical
      vessels and 87% displayed A beta deposits in meningeal vessels. The cerebral
      cortex of the oldest animal (15 years) contained a substantial density of
      deposits. A beta-immunoreactive plaques were found predominantly in association
      cortical zones followed by a lower density in paralimbic cortical areas. Deposits
      within vessels were most frequent in occipital cortex. A beta40 was found
      primarily in vascular deposits, while A beta42 was present in plaques.
      Approximately 20% of plaques and most vascular deposits displayed thioflavin S
      staining, indicative of the presence of fibrillar A beta. Varying proportions of
      A beta deposits contained acetylcholinesterase or butyrylcholinesterase
      activities and apolipoprotein E and alpha1-antichymotrypsin immunoreactivity. A
      few plaques contained immunoreactivity for amyloid precursor protein in swollen
      neurites. However, no abnormally phosphorylated tau immunoreactivity was present
      in these neurites. Survival analysis in a colony of marmosets indicated that only
      6% of animals can be expected to survive beyond 7 years of age. These results
      indicate that the aged marmoset brain displays A beta deposits with a
      distribution and chemical composition similar to those found in the human. These
      similarities suggest that the aged marmoset may be a useful lower primate model
      for the study of the pathological effects of A beta. However, the relatively
      small number of animals which can be expected to reach old age severely limits
      the utility of this species as a model of A beta deposition.

PMID- 11837749
TI  - Fetal ependymoma associated with Down's syndrome.
AB  - Down's syndrome (DS) is the most common multiple malformation syndrome occurring
      in humans and is associated with an increased risk of childhood malignancies, in
      particular leukemias. However, solid tumors seem to be underrepresented in DS
      patients and brain tumors occurring in association with DS have so far been
      limited to sporadic case reports, predominantly in children and young adults. We
      present the first case of an ependymoma associated with DS. This is also the
      youngest patient with DS suffering from a brain tumor as well as the first case
      in the English literature of a fetal ependymoma. The tumor was discovered
      incidentally at autopsy in a female fetus with DS after amniocentesis and
      termination of pregnancy in the 19th gestational week. Neuropathological
      examination revealed a tumor of 3x2x1 mm attached to the medulla oblongata
      rostrally of the floor of the fourth ventricle. Histologically, the ependymoma
      was moderately cellular and well demarcated with numerous perivascular
      pseudorosettes. Immunohistochemistry showed strong reactivity for GFAP, in
      particular of the fibrillary elements of the pseudorosettes, while the neuronal
      marker synaptophysin was not expressed. The Ki67/MIB-1 proliferation index was
      0.5%.

PMID- 11837750
TI  - Mixed multiple system atrophy and progressive supranuclear palsy: a clinical and
      pathological report of one case.
AB  - We report a patient who showed pathological features of both multiple system
      atrophy (MSA) and progressive supranuclear palsy (PSP) at autopsy. The clinical
      features included severe cerebellar ataxia, autonomic failure, and rigid-akinetic
      parkinsonism. The clinical diagnosis was MSA. Pathological examination showed
      severe neuronal loss with gliosis in the putamen, substantia nigra, inferior
      olive, and the pontine nucleus, and numerous glial cytoplasmic inclusions. In
      addition, moderate neuronal loss with gliosis was observed in the globus pallidus
      and subthalamic nucleus, and neurofibrillary tangles and tufted astrocytes were
      seen in the basal ganglia and the brain stem. These findings indicate that the
      patient had both MSA and PSP. Double-labeling immunofluorescence in the brain
      stem showed alpha-synuclein immunoreactivity localized in the oligodendrocytes
      and phosphorylated tau immunoreactivity in the neurons and the glia. Co-existence
      of synucleinopathy and tauopathy is rare.

PMID- 11837748
TI  - Increased expression of manganese superoxide dismutase is associated with that of
      nitrotyrosine in myopathies with rimmed vacuoles.
AB  - Oxidative stress has been suggested as one of the pathogenetic mechanisms of
      inclusion body myositis (IBM). To study the role of antioxidant enzymes in
      myopathies with rimmed vacuoles, we examined expressions of copper, zinc
      superoxide dismutase (Cu, Zn-SOD) and manganese superoxide dismutase (Mn-SOD),
      and the relationship between SODs and other proteins localized in rimmed vacuoles
      in muscle biopsy specimens from three cases of sporadic IBM and two of distal
      myopathy with rimmed vacuoles (DMRV) as well as eight control cases of myopathies
      without rimmed vacuoles. Immunoblot analysis showed distinct protein bands of
      both SODs in IBM and DMRV using subtype-specific antibodies. Intensities of
      immunoreactive bands for Mn-SOD in IBM and DMRV were stronger than those in the
      control cases. Immunohistochemistry disclosed accumulation of both SODs in
      vacuolated muscle fibers in all cases of IBM and DMRV. Immunoreactivity for Mn
      SOD was often colocalized with that of nitrotyrosine, cytochrome oxidase, tau,
      and lysosome-associated membrane proteins 2 (LAMP-2) in vacuolated fibers. Some
      of the Cu, Zn-SOD-positive vacuolated fibers were associated with ubiquitin. The
      two SODs may have different roles for cell protection, and the expression of Mn
      SOD is associated with nitric oxide-induced oxidative damage in myopathies with
      rimmed vacuoles.

PMID- 11837751
TI  - Erectile dysfunction and sildenafil citrate.

PMID- 11837752
TI  - Hypertension in the elderly.
AB  - OBJECTIVES: To study the clinical profile of hypertension in the elderly,
      development of end organ complications and the effect of hypertension with other
      risk factors in producing these complications. METHODS: One hundred and thirty
      six elderly patients attending the Hypertension Clinic were included in the
      study. A detailed history was taken that included presenting illness, family
      history of hypertension, diabetes, coronary artery disease, dyslipidaemia and
      history of addictions. Physical examination included systemic examination with
      measurement of waist to hip ratio and fundoscopy for retinopathy. Renal and liver
      function tests (RFT, LFT), blood sugar, lipid profile, X-ray chest,
      electrocardiography (ECG), 2-D echocardiography, abdominal ultrasound and
      computed tomography (CT) scan head (if indicated) were other important
      investigations done. RESULTS: Seventy-nine patients were in the age group of 60
      65 years, of which 42 (30.9%) were males. Headache was the commonest chief
      complaint in 77.9% patients; whereas 24 patients were asymptomatic. Obesity,
      diabetes, alcohol, dyslipidaemia and family history were important determinants
      of hypertension. Lipid profile was abnormal in 55.9% patients. Isolated systolic
      hypertension (ISH) was found in 56.6% patients. Grade II hypertensive retinopathy
      was observed in 29.4% patients with uncontrolled blood pressure. Left ventricular
      hypertrophy (LVH) was the commonest ECG manifestation seen in 36.8% patients of
      which 26.5% had uncontrolled blood pressure. LVH could be diagnosed in 46.4%
      patients by 2-D echo. Patients with uncontrolled blood pressure and ISH had
      increased incidence of cardiovascular and cerebrovascular complications.
      Cardiovascular complications were seen in 19.1% patients having dyslipidaemia and
      hypertension. Cerebrovascular complications were seen in 15.4% patients having
      hypertension with LVH. Treatment included calcium channel blockers and/or other
      drugs. CONCLUSIONS: The elderly hypertensive patients tend to have ISH. Family
      history of hypertension is an important determinant of hypertension. Uncontrolled
      hypertension, ISH, LVH and other associated risk factors are responsible for
      cardiovascular and cerebrovascular morbidity.

PMID- 11837753
TI  - Acute renal failure complicating rifampicin therapy.
AB  - BACKGROUND: Since 1971, 55 case-reports of rifampicin-induced acute renal failure
      (ARF) have been published. Covic et al described 60 consecutive cases of
      rifampicin-induced ARF during a period of eight years (1987-1995) from Iasi
      Dialysis Centre, Romania. The systenic data on this condition are not available,
      in view of the anecdotal nature of the observation from our country. OBJECTIVE:
      The aims of study were to analyze clinical features, course and outcome of ARF
      complicating rifampicin therapy at our centre. METHODS: We retrospectively
      studied prevalence, clinical presentations and renal histology and outcome of 11
      cases (eight males, three females, aged 42-72 years) who were referred to
      Nephrology Unit of University Hospital, Varanasi for acute renal failure
      following retreatment with rifampicin between period of 1994-1999. RESULTS: The
      gastrointestinal symptoms (abdominal pain, nausea and vomiting) and 'flu like'
      (fever, weakness and body ache) syndrome were the most frequent presenting
      features. The clinical signs of intravascular hemolysis were observed in four
      cases. The commonest laboratory findings included: Anaemia (7), leukocytosis (5),
      thrombocytopenia (3) and toxic hepatitis in (2) patients. Toxic hepatitis,
      hemolysis and ARF was seen in one patient in combination. The typical clinical
      features of allergic interstitial nephritis and acute tubular necrosis were seen
      in six and two patients respectively. Renal biopsy in three cases revealed;
      crescentic GN (1) and ATN in (2) patients. Acute renal failure complicating
      rifampicin accounted for 1.8% (11/607) of all ARF cases hospitalized in our
      centre during the study period. Renal function returned to normal in nine cases
      and one patient died on account of hepatic failure (toxic hepatitis). The
      patients with crescentic GN remained anuric and became dialysis dependent. Thus,
      clinical course of rifampicin induced ARF was favourable; with only one
      mortality, compared to a 18% mortality rate among all ARF patients. CONCLUSION:
      Acute renal failure complicating rifampicin therapy is not an uncommon condition,
      and typically occurs after reintroduction of rifampicin. The renal prognosis is
      usually favourable. Intermittent or interrupted therapy appears to be a
      significant risk factor for the development of acute renal failure.

PMID- 11837754
TI  - Wilson's disease in Eastern India.
AB  - INTRODUCTION: Wilson's disease is an inherited autosomal recessive (AR) disorder
      of copper metabolism transmitted by a mutant gene on chromosome 13q14-21 and
      results in abnormal accumulation of copper giving rise to protean manifestations.
      AIM: The aim is to study the clinical features, biochemical and radiological
      abnormalities of this disorder in Eastern India and the effect of treatment.
      RESULTS: Forty nine (n = 49) cases were studied over a period of 10 years.
      Majority of patients were male with mean age of onset being 11.13 years. They
      commonly presented with dysarthria, dystonia or drooling. The clinical features
      were dystonia (96%), silly smile (92%), dysarthria (80%), cognitive decline
      (71%), tremors (47%), bradykinesia (45%), etc. Family history suggested an
      autosomal recessive pattern. Sibling screening revealed that 4/8 (50%) were
      presymptomatic. All but one had presence of Keyser Fleischer (KF) ring in their
      cornea. Serum copper was reduced in 77% while ceruloplasmin was less in 94% of
      cases. The commonest abnormality seen in CT/MRI were in basal ganglia (74%)
      followed by white matter changes (59%) and brain stem changes (20.5%). The
      response to treatment was not as good and there was an initial deterioration in
      50% of cases. Only five patients could go back to their school. CONCLUSION:
      Wilson's disease have protean manifestations. All children with slowly
      progressive extrapyramidal syndrome should be investigated for it. Screening of
      all asymptomatic siblings for Wilson's disease must be carried out. Early
      institution of proper treatment and life long continuation is indicated in all.
      In the present series, an earlier age of onset of neurological signs and symptoms
      were seen; there was initial deterioration in 50% of cases and the response to
      treatment was not as good.

PMID- 11837755
TI  - Clinical evaluation of sibutramine in obese type 2 diabetic patients refractory
      to dietary management.
AB  - MATERIAL AND METHODS: An open, non-comparative study was carried out to assess
      the efficacy and toleration profile of sibutramine, a new antiobesity drug, in
      promoting weight loss in obese type 2 diabetes mellitus subject who failed to
      reduce weight after strict dietary control. Twenty seven patients completed the
      study. Sibutramine was started as a single morning dose of 10 mg and was
      subsequently increased to 15 mg daily if weight loss was not satisfactory. The
      total duration of the study was twelve weeks with followup at every four weeks.
      Effect of drug was monitored in terms of weight reduction, changes in body mass
      index, waist circumference, hip circumference, waist/hip ratio and other
      metabolic parameters. A fixed dietary prescription and concomitant therapy with
      drugs, if required and not likely to interfere with the trial therapy, was
      permitted but was not changed during the study period. RESULTS: At the end of 12
      week, mean weight reduction in study subjects was 4.16 kg (p < 0.001), the
      corresponding BMI decreased by 1.6 (p < 0.0001) and hip circumference by 3.68 (p
      < 0.001). However, there was no significant change in fasting blood glucose and
      Hb(A1c) values. CONCLUSION: The study indicates sibutramine to be an effective
      and well tolerated agent leading to significant reduction in parameter of obesity
      in obese type 2 diabetic subjects.

PMID- 11837756
TI  - Appropriate use of sildenafil citrate in male erectile dysfunction.

PMID- 11837757
TI  - Interleukin-2 as a therapeutic agent.
AB  - Interleukin-2 (IL-2) belongs to a class of soluble, regulatory proteins known as
      cytokines. It is a 133 amino acid glycoprotein secreted by T(H) lymphocytes and
      other cells following activation by antigens, mitogens and other cytokines. It
      stimulates the proliferation and cytotoxicity of T lymphocytes. It also enhances
      the microbicidal and cytotoxic activities of NK cells, B lymphocytes, macrophages
      and monocytes. IL-2 can now be produced in unlimited quantities by recombinant
      DNA technology and used therapeutically to modulate the immune system in a number
      of diseases. A number of different studies have demonstrated its therapeutic
      value in HIV +ve and AIDS patients. It has been approved by US-FDA for treatment
      of metastatic renal cell carcinoma (RCC) and metastatic melanoma. Routine
      detection of soluble IL-2 receptor in blood could be useful as a diagnostic
      marker in some autoimmune diseases. Agents that antagonize IL-2 find application
      as immunosuppressants. The main adverse effect of IL-2 is capillary leak syndrome
      caused by increased capillary permeability and extravasation of fluid. In days to
      come, IL-2 is likely to play an increasingly important role in management of
      viral infections, malignancies and a number of other diseases conditions.

PMID- 11837759
TI  - Aldosterone antagonists - revisited.

PMID- 11837758
TI  - The role of glucocorticoid pulse therapy in pulmonary involvement in
      leptospirosis.
AB  - OBJECTIVES: This study discusses incidence and clinical profile of pulmonary
      involvement in leptospirosis in South Gujarat. It also tries to evaluate the
      effect of high dose glucocorticoid pulse therapy (GPT) on it. METHOD: A study was
      carried out on hundred and two patients of suspected leptospirosis, referred to
      Government Medical College, New Civil Hospital, Surat between June 99 to
      September 99. The incidence, clinical profile, and specific investigations were
      studied in patients having pulmonary involvement. Some of the patients were given
      high dose glucocorticoid pulse therapy. Their outcomes were compared with those
      who had not been given glucocorticoid pulse therapy. RESULTS: Out of seventy
      seven seropositive patients 13 (16.8%) developed pulmonary involvement. Mortality
      was two out of eight patients in the group that received GPT and four out of five
      patients in the group that did not receive GPT. Two patients who died in the
      steroid treated group received the drug after 12 hours of onset of dyspnea.
      CONCLUSIONS: High dose GPT should be given as early as possible after the onset
      of dyspnea to all the patients with pulmonary involvement in leptospirosis.
      Further studies are required to establish the GPT as a standard regimen in
      treatment of pulmonary involvement in leptospirosis.

PMID- 11837760
TI  - Medical philately (medical personalities on stamps).

PMID- 11837761
TI  - Pictorial CME. Bronchogenic cyst with calcification.

PMID- 11837762
TI  - Primary angioplasty: the past, the present and the future.
AB  - Primary angioplasty (PTCA) in acute myocardial infarction has many theoretical
      advantages including better antegrade flow and reduced intracranial haemorrhage.
      However the improvement in the mortality and morbidity of primary angioplasty in
      the randomized trials from sophisticated centres has not been translated to the
      community setting. Primary PTCA is a suitable alternative to thrombolytic therapy
      if performed in a timely fashion by persons skilled in the procedure in a
      suitable laboratory. It is also recommended in patients with cardiogenic shock
      and in those with contraindications to thrombolytic therapy. Combination of
      thrombolytics and glycoprotein IIb/IIIa inhibitors with primary angioplasty may
      form the reperfusion strategy of the future.

PMID- 11837763
TI  - Adrenal histoplasmosis.
AB  - A 60 year old diabetic was admitted with the history of low grade fever and
      weight loss of six weeks duration. After investigations, he was detected to have
      bilateral adrenal masses which on biopsy proved to be due to histoplasmosis. He
      was treated with itraconazole and made complete recovery.

PMID- 11837764
TI  - Toxic epidermal necrolysis secondary to carbamazepine in a patient with human
      immunodeficiency virus infection.
AB  - Toxic epidermal necrolysis (TEN) is a rare but very serious dermatologic disorder
      and is seen more commonly in human immunodeficiency virus (HIV) infected
      patients. We present a case of TEN in HIV infected person secondary to
      carbamazepine who responded favourably to corticosteroids.

PMID- 11837765
TI  - Angioplasty of membranous obstruction of inferior vena cava.
AB  - Membranous obstruction of vena cava (MOVC) is a common cause of hepatic venous
      outflow obstruction. Surgical procedures utilized to relieve symptoms carry a
      high morbidity and mortality. A patient who presented with gradual onset ascites
      and dilated, tortuous veins over the anterior abdominal wall and the back was
      found to have MOVC by inferior vena cavogram. Balloon dilatation of the
      obstruction was done successfully through a transvenous approach. Following this,
      the patient improved remarkably. The procedure is safe, effective and easy to
      perform. This balloon angioplasty provides alternative method for treatment of
      membranous obstruction of vena cava.

PMID- 11837766
TI  - Severe panhypopituitarism and central diabetes insipidus following snake bite:
      unusual presentation as torsades de pointes.

PMID- 11837767
TI  - Oral histoplasmosis.

PMID- 11837768
TI  - Neurologic illness following post-exposure prophylaxis with purifiled chick
      embryo cell antirabies vaccine.
AB  - Clinical details of a neurologic illness simultating Guillain Barre syndrome
      developing in a patient after post-exposure prophylaxis with purified chick
      embryo cell (PCEC) anti-rabies vaccine is reported. Neurologic complication
      following PCEC vaccination has not been reported earlier.

PMID- 11837769
TI  - Phenytoin associated alopecia: drug induced lupus.

PMID- 11837770
TI  - Supraventricular tachycardia and psychiatric illness.

PMID- 11837771
TI  - Hypopituitarism after viperine bite.

PMID- 11837772
TI  - True hermaphrodite.

PMID- 11837773
TI  - Idiopathic calcinosis in a young boy.

PMID- 11837774
TI  - Familial parkinsonism with peripheral neuropathy.

PMID- 11837776
TI  - Malaria diagnosis: quantitative buffy coat versus conventional microscopy.

PMID- 11837775
TI  - Progressive dilated cardiomyopathy in a patient with hypereosinophilic syndrome
      despite prednisone induced hematological remission.

PMID- 11837777
TI  - Role of cardiophone in the pre-hospital treatment of acute myocardial infarction.

PMID- 11837778
TI  - Cardiac arrhythmia following intravenous quinine therapy.

PMID- 11837779
TI  - Insulin resistance syndrome (syndrome X) and hypothyroidism.

PMID- 11837780
TI  - Neuroleptic malignant syndrome--atypical presentation.

PMID- 11837781
TI  - Persistent fever in a case of typhoid--an unusual cause of neuroleptic malignant
      syndrome.

PMID- 11837782
TI  - Silent background noise of iron deficiency anaemia.

PMID- 11837783
TI  - Study of alendronate in avascular necrosis of bone.

PMID- 11837784
TI  - Compartmentalization of macrophage inflammatory protein-2, but not cytokine
      induced neutrophil chemoattractant, in rats challenged with intratracheal
      endotoxin.
AB  - An important feature of the pulmonary inflammatory response is that the
      production of certain cytokines and chemokines is largely confined to the lung.
      This study investigated the local and systemic responses of macrophage
      inflammatory protein-2 (MIP-2) and cytokine-induced neutrophil chemoattractant
      (CINC) in rats administered with either intratracheal or intravenous
      lipopolysaccharide (LPS). Intratracheal LPS induced a significant increase in MIP
      2 in bronchoalveolar lavage (BAL) fluid with no detectable MIP-2 in the plasma.
      In contrast, CINC was significantly increased in both BAL fluid and the plasma
      after intratracheal LPS challenge. Cell-associated MIP-2 was increased in the
      pulmonary-recruited neutrophils (PMNs) but not in the circulating PMNs in rats
      given intratracheal LPS. Cell-associated CINC was increased in both the recruited
      and circulating PMNs in these animals. Intravenous LPS caused a marked increase
      in plasma MIP-2 and CINC, whereas only a small elevation of both MIP-2 and CINC
      concentrations in BAL fluid was observed. The lack of CINC compartmentalization
      compared to MIP-2 implies that these C-X-C chemokines are regulated
      differentially and may have different effects upon polymorphonuclear leukocyte
      (PMN) recruitment into the alveolar space in response to intrapulmonary LPS or
      bacterial challenge.

PMID- 11837786
TI  - Ischemia alone is sufficient to induce TNF-alpha mRNA and peptide in the
      myocardium.
AB  - Over-production of tumor necrosis factor-alpha (TNF-alpha) following myocardial
      ischemia-reperfusion contributes to cardiac dysfunction, and anti-TNF-alpha has
      therapeutic potential for myocardial protection in cardiac surgery with
      obligatory ischemia. It remains unclear, however, whether myocardial TNF-alpha
      production occurs during ischemia and whether cardiac myocytes constitute a
      source of myocardial TNF-alpha. Ischemia alone has been shown to activate
      myocardial NF-kappaB. We hypothesized that ischemia alone is sufficient to induce
      myocardial TNF-alpha gene expression and peptide synthesis. We examined TNF-alpha
      production and NF-kappaB activation in the isolated rat heart subjected to global
      normothermic ischemia. Myocardial ischemia resulted in rapid IkappaB-alpha
      degradation and NF-kappaB activation. Immunofluorescence staining detected NF-KB
      intranuclear translocation primarily in myocardial interstitial cells. Ischemia
      alone induced a time-dependent increase in myocardial TNF-alpha. TNF-alpha
      peptide increased to 20.3+/-3.0 pg/mg after 25 min of ischemia (P < 0.05 vs 8.9+/
      2.0 pg/mg in perfusion control). TNF-alpha was also localized to myocardial
      interstitial cells. Increased TNF-alpha peptide level correlated with TNF-alpha
      mRNA expression. We conclude that ischemia alone induces TNF-a gene expression
      and peptide synthesis in the myocardium that are associated with NF-kappaB
      activation. Non-myocytes constitute the main source of myocardial TNF-alpha
      following ischemia. The results suggest that therapeutic strategies attempting to
      decrease myocardial TNF-alpha production need to be applied before or in the
      early phase of ischemia.

PMID- 11837785
TI  - The actin cytoskeleton: an essential component for enhanced TNFalpha production
      by adherent monocytes.
AB  - Monocyte adherence induces the formation of focal adhesions, the interaction
      sites of intracellular signaling molecules and cytoskeletal proteins such as
      actin. We previously demonstrated that adherence potentiates human monocyte LPS
      induced TNFalpha production. Hence, we hypothesized that the actin cytoskeleton
      is integral to adherence-induced priming for enhanced LPS-induced TNFalpha
      production. In contrast to nonadherent cells, LPS induced significant
      transcription of TNFalpha mRNA and production of TNFalpha in adherent monocytes.
      Disrupting the actin cytoskeleton with cytochalasin D (CD) in adherent monocytes
      inhibited LPS-induced TNFalpha production by 55%, thereby abrogating adherence
      induced priming. Moreover, CD pretreatment abrogated adherence-induced activation
      of Pyk2, a major focal adhesion kinase, and ERK 1/2, a component of the mitogen
      activated protein kinase (MAPK) signaling pathway, and it completely inhibited
      LPS-induced ERK 1/2 activation. However, CD treatment of nonadherent monocytes
      failed to inhibit cytokine production. In conclusion, the actin cytoskeleton is
      integral in the reprogramming of the monocyte for enhanced cytokine production
      and in maintaining this "primed" state.

PMID- 11837787
TI  - Induced hypothermia after high-energy soft-tissue injury and subsequent
      hemorrhagic shock.
AB  - Many cases of hypothermia (HT) occur in trauma victims subjected to soft tissue
      injury and hemorrhage. The aim of the present study was to study the effects of
      HT on the combination of these insults. A standardized gunshot wound was
      inflicted on the right hind leg of 14 anesthetized piglets. They were then
      exsanguinated of 50% of their blood volume and randomized to normothermia or HT
      (30 degrees C). The animals were observed for 4 h after the injury with
      measurements of hemodynamics, oxygen consumption, and of plasma catecholamines
      and electrolytes. The insults reduced cardiac output and the arterial pressure by
      approximately 50%, but no further reduction occurred when HT was induced. The
      oxygen extraction ratio increased from approximately 35% to 75% in both groups.
      The gradual reduction of oxygen consumption in HT animals (P < 0.05) decreased
      the oxygen extraction ratio to around 50%. Heart rate, the serum potassium and
      creatinine concentrations, and the leukocyte counts were all maintained closer to
      baseline in the presence of HT. Hypothermia tended to decrease oxygen extraction
      and was associated with less evidence of tissue injury. These effects are
      potentially beneficial in soft-tissue trauma combined with hypovolemia.

PMID- 11837788
TI  - Sesquiterpene lactone parthenolide, an inhibitor of IkappaB kinase complex and
      nuclear factor-kappaB, exerts beneficial effects in myocardial reperfusion
      injury.
AB  - Sesquiterpene lactones are extracts of common medicinal Asteracae plants used in
      folk medicine for their anti-inflammatory activity. Recently, in vitro studies
      have shown that these compounds may interfere with pro-inflammatory gene
      regulation. This study examines the effects of parthenolide, a sesquiterpene
      lactone, in experimental myocardial ischemia and reperfusion. Myocardial injury
      was induced in rats by 30 min occlusion and 120 min reperfusion of the left
      coronary artery. Parthenolide (250 or 500 microg/kg) or vehicle (0.05% Tween 80,
      1 mL/kg) was administered intraperitoneally 10 min before reperfusion. In vehicle
      treated rats, ischemia and reperfusion caused myocardial injury, as evaluated by
      infarct size, serum levels of creatine phosphokinase and by histological
      examination. Elevated tissue levels of myeloperoxidase activity were indicative
      of a significant infiltration of neutrophils. This event paralleled the
      occurrence of oxidative damage, as evaluated by a marked increase in tissue
      malondialdehyde levels. These inflammatory events were preceded by activation of
      the IkappaB kinase complex (IKK) and partial disappearance of inhibitor
      kappaBalpha (IkappaBalpha) in the cytosol and translocation of the nuclear factor
      kappaB (NF-kappaB) to the nucleus, as early as 15 min after reperfusion.
      Administration of parthenolide ameliorated myocardial injury, lowered serum
      creatine phosphokinase activity, and reduced neutrophil infiltration and the
      subsequent oxidative damage. These beneficial effects were associated with
      inhibition of IKK activity, enhanced stability of IkappaBalpha, and inhibition of
      nuclear translocation of NF-kappaB. The results of this study suggest that
      parthenolide may be beneficial for the treatment of reperfusion-induced
      myocardial damage by inhibition of the IKK/NF-kappaB pathway.

PMID- 11837790
TI  - Nitric oxide directly impairs intestinal barrier function.
AB  - Excess production of nitric oxide (NO) has been implicated in endotoxin-induced
      loss of gut barrier function in vivo. Thus, we tested the direct effect of NO on
      the barrier function of intestinal mucosal membranes suspended ex vivo in Ussing
      chambers and on IEC-6 enterocyte monolayers. In these experiments, ex vivo
      mounted ileal membranes or IEC-6 cell enterocyte monolayers were exposed to the
      NO donor, S-nitroso-N-acetyl-penicillamine (SNAP) over a dose range (10 microm to
      2 mM) or medium. SNAP at concentrations of 1 or 2 mM, but not 10 or 100 microM,
      increased the rates of bacterial translocation (BT) across both the ileal
      membranes and the IEC-6 monolayers by >1 log (P < 0.05), as well as the
      permeability of the IEC-6 monolayers to phenol red (P < 0.05). The ileal
      membranes exposed to 1 or 2 mM SNAP for 3 h manifested histologic evidence of
      mucosal injury and decreases in electrical resistance and potential difference
      values (P < 0.05), while the IEC-6 cells exposed to SNAP for 18 h had increased
      levels of cell death (P < 0.05). Since NO produced locally by stimulated
      enterocytes could contribute to barrier dysfunction, NO production, iNOS mRNA
      levels, and monolayer permeability were measured in enterocytes (IEC-6 and Caco
      2) exposed to medium, endotoxin (lipopolysaccharide [25 microg/mL]) or a cytokine
      mixture (IL-1beta 10 ng/mL, TNF-alpha 10 ng/mL, and INF-gamma 250 U/mL) for 6 or
      24 h. Endotoxin increased NO production, iNOS mRNA expression, and monolayer
      permeability in the IEC-6, but not the Caco-2 cells, while exposure to the
      cytokine mixture increased both NO production, iNOS mRNA expression, and
      monolayer permeability in both the IEC-6 and Caco-2 cell lines. Based on the
      results of these studies it appears that NO can directly increase ileal mucosal
      membrane and enterocyte monolayer permeability and BT and that increased NO
      production and iNOS mRNA expression is associated with endotoxin- and/or cytokine
      induced loss of enterocyte monolayer barrier function.

PMID- 11837789
TI  - Bioglass attenuates a proinflammatory response in mouse peritoneal endotoxicosis.
AB  - Bioglass is a bioactive, resorbable ceramic particle that was developed to assure
      binding to living tissues. Bioglass is currently employed to fill osseus defects
      in oral surgery, and it possesses both unique anti-inflammatory and antimicrobial
      properties. In an effort to determine whether Bioglass may be useful as an
      adjunct anti-inflammatory device in local inflammatory processes, we examined
      whether exposure of the peritoneal cavity to Bioglass would induce a pro- or anti
      inflammatory response, and then modulate a subsequent proinflammatory response to
      endotoxin. Three- to fifty-milligram doses of 5 pm Bioglass were administered
      intraperitoneally in C57BL/6 mice. Total leukocyte, myeloperoxidase, and cytokine
      levels in the peritoneal wash fluid were determined. In addition, the peritoneal
      cavity was preexposed to Bioglass, and was then subjected to a subsequent
      endotoxin administration. All doses of Bioglass were found to induce a
      significant peritoneal IL-6 response; however, Bioglass did not induce a TNF
      alpha, IL-1alpha, IL-10, or a white cell recruitment into the peritoneal lavage
      fluid. Pretreatment of the peritoneal cavity with Bioglass produced a transient
      reduction in the proinflammatory response to endotoxin. We conclude that exposure
      to Bioglass produces an IL-6 response without concurrent expression of TNF-alpha
      or IL-1alpha. Bioglass appears to transiently suppress the inflammatory response
      to endotoxin, possibly through the early induction of IL-6. These findings
      suggest that Bioglass may offer a unique approach in modifying the inflammatory
      response in local tissue compartments.

PMID- 11837791
TI  - The effects of repeated dosing with 7.5% sodium chloride/6% dextran following
      uncontrolled intra-abdominal hemorrhage.
AB  - The use of hypertonic saline Dextran (HSD) for resuscitation following trauma has
      many potential benefits, especially for the treatment of military casualties, but
      there is very limited data on the responses following multiple dosing with this
      fluid. The effects of a second dose of hypertonic saline dextran for
      resuscitation of uncontrolled intra-abdominal haemorrhage were studied in an
      experimental model. Under general anaesthesia, 17 large white pigs (weight range,
      48-67 kg) were subjected to uncontrolled hemorrhage produced by a tear in the
      common iliac artery. This resulted in a significant (P < 0.01) reduction of both
      mean arterial pressure (MAP) and cardiac index. One hour after injury, animals
      were assigned to one of three groups, receiving either no resuscitation (Group
      A), or two doses of HSD (at a dose rate of 4 mL/kg), administered either 1 and 4
      h after injury (Group B) or 1 and 7 h after injury (Group C). Animals were
      monitored for 12 h post-injury. A second infusion of HSD caused a significant
      hypernatremia and diuresis (P< 0.01) in both Groups B and C. There was a non
      significant rise in MAP in both treatment groups, and in Group B only, there was
      a significant increase in cardiac index (P= 0.014). It is concluded that repeat
      administration of HSD for the resuscitation of uncontrolled hemorrhage results in
      limited cardiovascular improvements, but that the metabolic sequelae are
      potentially detrimental to survival.

PMID- 11837792
TI  - Pulmonary leukostasis and the inhibition of airway neutrophil recruitment are
      early events in the endotoxemic rat.
AB  - Neutrophil (polymorphonuclear leukocyte [PMN]) migration into pulmonary airspaces
      is a prerequisite for clearance of bacteria commonly found in nosocomial
      pneumonia. Patients at risk for nosocomial pneumonia often experience
      endotoxemia, and neutrophil dysfunction is associated with endotoxemia in both
      humans and animals. Using a rodent model of endotoxemia-associated pneumonia, we
      characterized the altered kinetics of pulmonary PMN trafficking and addressed the
      roles of platelets, tumor necrosis factor (TNF), and products of complement
      activation as potential mediators in the modulation of PMN migratory function. In
      male Sprague-Dawley rats made endotoxemic with intravenously (i.v.) administered
      endotoxin (lipopolysaccharide [LPS]), recruitment of PMNs into the lung airspaces
      in response to intratracheally (i.t.) instilled LPS was inhibited. In animals
      given IT LPS alone (0.5 mg/rat), numbers of airway PMNs were significantly
      elevated by 2 h, and immunohistochemical evaluation revealed PMNs in alveolar
      airspaces, alveolar walls, and in interstitium surrounding large airways. LPS (2
      mg/kg i.v.) caused neutropenia and pulmonary PMN sequestration within 15 min of
      administration. Inhibition of airway PMN accumulation occurred by 30 min and
      lasted for at least 6 h after i.v. LPS. Factors present or activated after 30 min
      of endotoxemia were hypothesized to mediate the inhibitory effect of i.v. LPS. We
      found that pretreatment of rats with cobra venom factor to deplete complement
      (and C5a production) or immunodepletion of platelets or TNF did not affect the
      ability of i.v. LPS to inhibit pulmonary PMN recruitment or to cause pulmonary
      leukostasis. In summary, our results show that the inhibitory effects of i.v. LPS
      on PMN trafficking are rapid and persist for several hours and suggest that
      neither TNF, C5a, nor platelets are sufficient to mediate the inhibitory
      response.

PMID- 11837793
TI  - Factor Xa-inhibitor (DX-9065a) modulates the leukocyte-endothelial cell
      interaction in endotoxemic rat.
AB  - Abnormalities of vascular endothelial function and coagulation play important
      roles in the development of septic organ dysfunction. DX-9065a is a novel Factor
      Xa inhibitor that is expected to modulate both coagulation and endothelial
      function. The purpose of this study is to examine the effect of DX-9065a on
      leukocyte-endothelial interaction. Rats were injected with 1.0 mg/kg of endotoxin
      simultaneously with saline, (placebo group), 0.3 mg/kg DX-9065a (low-dose group),
      or 3.0 mg/kg DX-9065a (high-dose group; n = 6 in each group). At 1 and 3 h after
      injection, the mesenteric microcirculation was observed under intravital
      microscopy. In addition, TNF, IL-6, alanine aminotransferase (ALT), blood urea
      nitrogen (BUN), and lactate levels were measured. The number of leukocytes
      adhering to the endothelium was significantly reduced in both the high-dose and
      low-dose groups (P < 0.05 for both, compared to the control group). A comparison
      of the cytokine levels showed that the peak levels in the treatment groups tended
      to be lower. Markers of organ damage also showed less increase in the treatment
      groups (P < 0.05 for both treatment groups compared to the control group). In
      summary, the Factor Xa inhibitor DX-9065a showed a protective effect on the
      microcirculation of endotoxemic rats by attenuating leukocyte-endothelial
      interaction. Although the mechanism for this effect could not be fully
      elucidated, suppression of both excessive coagulation and cytokine production
      appear to play a role.

PMID- 11837794
TI  - Suppressors of cytokine signaling (SOCS): inhibitors of the JAK/STAT pathway.
AB  - The suppressors of cytokine signaling (SOCS) are recently identified inhibitors
      of cytokine and growth factor (GF) signaling that act via the Janus kinase
      (JAK)/signal transducers and activators of transcription (STAT) pathway. Cytokine
      mediated JAK/STAT signaling controls a number of important biologic responses,
      including immune function, cellular growth, differentiation, and hematopoieses.
      The SOCS family consists of eight proteins: CIS and SOCS1-SOCS7, which contain a
      central SH2 domain, a conserved C-terminus referred to as the SOCS box, and a
      unique N-terminus. The expression of SOCS-1 to -3 and CIS is induced by cytokine
      or GF stimulation, resulting in the inhibition of JAK/STAT-mediated cytokine
      signaling by what appears to be a classic negative feedback loop. In this article
      we review cytokine/GF signaling by the JAK/STAT pathway, discovery of the SOCS
      family, the regulation of SOCS expression, mechanism(s) of SOCS action, and we
      summarize some of the biochemical and genetic studies investigating the
      physiologic role of SOCS in regulating cytokine activity.

PMID- 11837795
TI  - Heat shock inhibits tnf-induced ICAM-1 expression in human endothelial cells via
      I kappa kinase inhibition.
AB  - The pulmonary vascular endothelium plays a critical role in lung inflammation. As
      a result of proinflammatory cytokine expression, adhesion molecules are
      upregulated on the surface of the endothelial cells. Adhesion molecules
      facilitate recruitment of leukocytes and thus, have been targeted for potential
      anti-inflammatory strategies. Prior induction of the stress response through
      thermal stimulation, or heat shock, alters proinflammatory gene expression by
      attenuating NF-kappaB signaling. As intercellular adhesion molecule-(ICAM) 1
      expression is, in part, NF-kappaB-dependent, we hypothesized that heat shock
      would inhibit ICAM-1 expression. Heat shocking endothelial cells resulted in heat
      shock protein (HSP) expression as measured by HSP-70 induction, and decreased TNF
      alpha-induced ICAM-1 expression in a manner that appeared to be transcriptionally
      mediated. Following heat shock, decreased TNF-alpha-induced NF-kappaB activation
      was observed and was associated with preservation of IkappaB-alpha and a decrease
      in phosphorylated IkappaB-alpha that correlated to inhibition of I kappa kinase
      (IKK) activity. Interestingly, exposing respiratory epithelial cells to heat
      shock, which results in NF-kappaB inhibition, did not affect TNF-induced ICAM-1
      expression. We conclude that heat shock decreases endothelial cell ICAM-1
      expression via inhibition of IKK activity.

PMID- 11837797
TI  - Enzyme replacement therapy for Fabry disease, an inherited nephropathy.
AB  - Fabry disease, an X-linked lysosomal storage disease, results from the deficient
      activity of the enzyme alpha-galactosidase A (alpha-Gal A) and the progressive
      accumulation of globotriaosylceramide (GL-3) and related glycosphingolipids. In
      classically affected males with this inherited nephropathy, early and marked GL-3
      deposition in the podocytes leads to proteinuria in childhood or adolescence.
      With increasing age, GL-3 deposition in renal microvascular endothelial cells,
      and to a lesser extent in interstitial and mesangial cells, leads to renal
      insufficiency in the third to fifth decades of life. Recently identified "renal
      variants" who lack the classical disease manifestations of acroparesthesias,
      angiokeratoma, hypohidrosis, and characteristic corneal/lenticular opacities also
      develop renal failure. In contrast, "cardiac variants" who also lack the
      classical phenotype, develop proteinuria in adulthood, but survive a normal
      lifespan without developing renal failure. Here, we review the renal involvement
      and pathology in the classical, renal and cardiac variant phenotypes, and present
      highlights of the preclinical studies and clinical trials that demonstrated the
      safety and effectiveness of recombinant alpha-Gal A replacement for this
      inherited nephropathy.

PMID- 11837796
TI  - A nitric oxide scavenger protects against pulmonary inflammation following
      hemorrhagic shock.
AB  - Hemorrhagic shock (HS) elicits an inflammatory response characterized by
      increased cytokine production and recruitment of PMN which we previously found to
      be iNOS dependent. In this study we attempted to remove excess induced-NO by
      administration of the NO scavenger, NOX, with the goal of suppressing
      proinflammatory signaling and reducing organ damage. Rats subjected to HS (MAP =
      40 mmHg for 100 min) followed by resuscitation and examined 24 h later
      demonstrated histological signs of lung injury including pulmonary edema as well
      as an 8.6-fold increase in MPO-positive PMN. These events were accompanied by a
      3.9-fold increase in mRNA levels for IL-6, 3.7-fold for ICAM-1, 3.5-fold for IL
      1beta, and 7.3-fold for TNFalpha compared to sham animals. Immunostaining of the
      lungs of shock animals demonstrated IL-6 protein localized to cells lining the
      luminal sides of bronchiols. These animals also demonstrated a 2-fold and 5.5
      fold increase in activation of NF-kappaB and Stat3 (an IL-6 signaling
      intermediate), respectively. Administration of NOX (30 mg/kg/h beginning at 60
      min of shock for total of 4.5 h) resulted in reduced lung injury as measured by a
      46% reduction in PMN infiltration, a 20% decrease in wet-to-dry ratio, and
      improved arterial blood gases. NOX reduced proinflammatory signaling in the lung
      as demonstrated by a 62% decrease in NF-kappaB binding, 47% reduction in Stat3
      binding, a reduction in mRNA expression of 48% for IL-6, 57% for ICAM-1, 67% for
      IL-1beta, and 64% for TNFalpha, as well as a marked reduction in the intensity of
      IL-6 protein staining. These data indicate that NOX prevents lung injury in this
      HS model, possibly through downmodulation of proinflammatory signaling and the
      shock-induced inflammatory response.

PMID- 11837798
TI  - Type 2 angiotensin II receptor expression in human renal allografts: an
      association with chronic allograft nephropathy.
AB  - AIMS: The renin-angiotensin system (RAS) has been implicated in renal fibrosis
      through activation of the type I angiotensin II (Ang II) receptor (AT1R). Whether
      the other predominant Ang II receptor, the type 2 Ang II receptor (AT2R), has a
      fibrotic or sparing role in adult human renal tissue is unknown. MATERIALS AND
      METHODS: We used the reverse-transcription polymerase chain reaction (RT-PCR) to
      assess intragraft AT2R mRNA expression in biopsy samples from 23 renal transplant
      recipients. Potential correlations between intragraft AT2R mRNA. matrix
      modulating genes and histologic evidence of chronic rejection were assessed.
      RESULTS: AT2R mRNA was confirmed by sequence analysis of the RT-PCR product. AT2R
      mRNA expression directly correlated with angiotensinogen (Spearman correlation
      coefficient (r(s)) 0.72; p = 0.0011) mRNA expression, and interestingly, AT2R
      mRNA inversely correlated with inflammatory gene expression in the biopsy
      samples. However, AT2R mRNA directly correlated with transforming growth factor
      beta (TGF-beta) (r(s) 0.59: p = 0.044), matrix metalloproteinase-1 (MMP-1) (r(s)
      0.83; p = 0.001), tissue inhibitor of metalloproteinase-2 (TIMP-2) (r(s) 0.74; p
      = 0.001) and TIMP-3 (r(s) 0.80; p = 0.001) mRNA expression. Moreover, AT2R mRNA
      and protein expression was significantly greater in the patients with biopsy
      proven chronic allograft nephropathy (n = 9; p = 0.045 vs. no chronic allograft
      nephropathy and donor biopsy samples for mRNA analyses). CONCLUSIONS: These data
      demonstrate that AT2R mRNA is expressed in adult human renal tissue in the
      setting of renal transplantation. Its apparent association with matrix-modulating
      genes raises the hypothesis that AT2R mRNA expression may be linked with
      extracellular matrix regulation in the setting of chronic allograft nephropathy.

PMID- 11837799
TI  - HLA matching for simultaneous pancreas-kidney transplantation in the United
      States: a multivariable analysis of the UNOS data.
AB  - BACKGROUND: As the incidence of diabetic nephropathy increases, especially in
      minority populations, more simultaneous pancreas-kidney (SPK) transplants are
      being performed both in the United States and worldwide. The role of matching on
      SPK outcomes and organ allocation remains controversial. The purpose of this
      analysis was to determine the influence of HLA matching using currently employed
      criteria on 5-year SPK graft survival. METHODS: We performed an analysis of all
      3,316 SPK transplants performed in the United States reported to the United
      Network for Organ Sharing (UNOS) between December 31, 1988 and December 31, 1994.
      Kaplan-Meier unadjusted 1- and 5-year graft survival with log rank comparisons
      and Cox multivariable regression models that adjusted for 12 confounding
      variables were used to analyze the influence of HLA matching on outcomes.
      RESULTS: Despite low-grade HLA or DR matching or high levels of common reactive
      groups (CREG) mismatching, 1- and 5-year allograft survival rates were 90% and
      78% for kidney, and 85% and 75% for pancreas transplantation. CONCLUSIONS: SPK
      transplantation is associated with excellent outcomes independent of the level of
      HLA matching. These data support the hypothesis that SPK transplants need not be
      allocated based on matching criteria, thus minimizing organ ischemia time and
      promoting a more racially equitable allocation for SPKs in the US today.

PMID- 11837800
TI  - Resistive index in chronic nephropathies: predictive value of renal outcome.
AB  - The study of renovascular resistances by color Doppler ultrasound has become a
      useful diagnostic resource for nephrologists. In recent nephrological literature,
      many papers deal with the correlations between resistive index, anatomo
      pathological patterns and renal function. AIMS: In our study, we have tried to
      discover if resistive index represents a prognostic index of progressive renal
      failure. MATERIAL AND METHODS: To this purpose we compared renal resistive index
      and blood creatinine obtained from 28 nephropathic patients at their first
      control, with blood creatinine values after a 3-year follow-up period. Using a
      linear regression test, we found a strong correlation between the initial value
      of resistive index and the value of creatinine variation (p = 0.006). RESULTS:
      All of the patients with normal resistive index at the beginning maintained a
      stable renal function. Conversely, the patients with high resistive index at
      their first control showed a progressive renal failure. CONCLUSION: Our study
      shows the reliability of resistive index in the prognostic evaluation of renal
      outcome.

PMID- 11837801
TI  - Racial differences in parathyroid hormone levels in patients with secondary
      hyperparathyroidism.
AB  - AIM: African-Americans (AA) with normal renal function have higher parathyroid
      hormone (PTH) levels than Caucasians (C). This difference was also noted in cross
      sectional studies of patients on dialysis. In this study, we evaluated patients
      with end-stage renal disease who have just began dialysis and who were not
      receiving any vitamin D therapy. METHODS: A total of 363 patients were recruited
      (C: 260; AA: 103). All patients had serum calcium, phosphorus, alkaline
      phosphatase and intact PTH (iPTH) levels measured within 3 months of initiating
      dialysis. RESULTS: Serum PTH levels were significantly higher in AA vs. C (383 +/
      33 vs. 246 +/- 19, p < 0.001). This difference was present despite similar
      calcium, phosphorus and alkaline phosphatase levels between the 2 groups and
      regardless of gender or diabetes status. However, PTH levels in patients younger
      than 47 years of age were similar in both groups. CONCLUSION: PTH levels in ESRD
      patients over 47 years of age are higher in AA compared to C. The difference is,
      in part, due to an age-dependent reduction in PTH seen only in C. Further studies
      are needed to understand the mechanisms of these racial differences and to verify
      whether they mirror similar alterations at the level of the end-organ tissue.

PMID- 11837802
TI  - The usefulness of F-18 deoxyglucose whole-body positron emission tomography (PET)
      for re-staging of renal cell cancer.
AB  - PURPOSE: The use of whole-body PET for re-staging of renal cell carcinoma has not
      been investigated. The aim of the current study was to examine the diagnostic
      accuracy and clinical usefulness of whole-body PET imaging for re-staging of
      renal cell cancer. PATIENTS AND METHODS: Clinical PET was performed for re
      staging in 36 patients with advanced renal cell cancer. Written reports of
      imaging studies (including CT, MRI, US, plain film and bone scan), patient
      history, and extensive chart notes were used to define the clinical stage before
      PET (pre-PET stage). The written PET report was used to define the clinical stage
      after PET (PET stage). Reports were used to determine the accuracy of PET for re
      staging renal cell cancer and for defining biopsy proven lesions. Clinical
      parameters and biopsy proven lesions served as reference for the accuracy of PET
      for re-staging renal cell cancer. RESULTS: PET classified the clinical stage
      correctly in 32/36 patients (89%) and was incorrect in 4/36 (11%) (sensitivity
      and specificity: 87% and 100%). In 20 patients, 25 suspicious lesions were
      biopsied within 3.2 +/- 6.7 months of the PET study. Of these, 17 were malignant
      and 8 were benign. PET correctly classified 21/25 (84%) of the biopsied lesions
      (sensitivity and specificity: 88% and 75%). CONCLUSION: PET re-stages renal cell
      cancer with a diagnostic accuracy of 89%. Its diagnostic accuracy for classifying
      biopsy proven anatomic lesions as malignant or benign was 84%. These findings
      suggest that PET is useful in characterizing anatomic lesions of unknown
      significance in patients with renal cell cancer.

PMID- 11837803
TI  - Nephrotic IgA nephropathy associated with disseminated tuberculosis.
AB  - A 35-year-old woman who had been suffering from ascites more than 3 months after
      the delivery of her first baby, developed generalized edema, pyrexia, pleural
      effusion, and right lower abdominal pain. The laboratory data revealed 5.6 g of
      24-hour urinary protein, increased ESR and CRP, a positive skin test for
      tuberculosis, and a positive culture fortuberculous bacilli from pleural
      effusion. A renal biopsy showed mild proliferative glomerulonephritis, IgA and C3
      depositions along the capillary loop, in the mesangium and also in the focal
      tubular basement membrane, and scattered membranolysis of the glomerular basement
      membrane in addition to paramesangial and intramembranous electron-dense
      deposits. A positive culture of tuberculous bacilli led anti-tuberculous drugs
      resulted in the complete disappearance of proteinuria, inflammation, and various
      organ manifestations. As far as we know, the association of tuberculosis with
      glomerulonephritis is an uncommon occurrence. In addition to describing this
      case, we also discussed the role of tuberculosis in the pathogenesis of
      glomerulonephritis, and reviewed the pertinent literature.

PMID- 11837804
TI  - Association of parvovirus B19 infection with acute glomerulonephritis in healthy
      adults: case report and review of the literature.
AB  - An otherwise healthy 20-year-old woman presented with an erythematous rash on her
      face as well as arthralgia and anemia. She also had systemic edema, proteinuria
      and hypertension. Laboratory data on admission showed hypocomplementemia, human
      parvovirus B 19 (HPV) DNA and both immunoglobulin (Ig) M and IgG antibodies to
      HPV in her serum. Renal biopsy specimens showed features of endocapillary
      glomerulonephritis under light microscopy. Electron microscopy showed massive
      subendothelial electron-dense deposits. No cause was probable other than immune
      complex-mediated glomerulonephritis associated with HPV infection. In a review of
      this and similar cases reported in the literature, several characteristic
      features come to light: female dominance, onset in the second or third decade of
      life, hypocomplementemia, histologic renal endocapillary and/or
      mesangioproliferative glomerulonephritis with subendothelial deposits and
      spontaneous recovery.

PMID- 11837805
TI  - A unique renal lesion in common variable immunodeficiency.
AB  - This article reports the case of a 33-year-old woman with common variable
      immunodeficiency (CVI) who developed renal failure 17 years after diagnosis and
      initiation of treatment with monthly IVIG. A renal biopsy revealed mesangial and
      paramesangial immune complex deposition and interstitial granulomatous
      infiltration. Renal function improved with oral corticosteroids, but did not
      return to normal. Decreasing the dose of IVIG had no effect on renal function.
      Immune dysfunction can be associated with both granulomatous disease and immune
      complex glomerulonephritis, or the latter may be related to chronic infection or
      immunoglobulin use. This is the first report of concomitant glomerular
      tubulointerstitial lesions in this immunodeficiency syndrome. Renal function
      should be closely followed in patients with CVI.

PMID- 11837806
TI  - Carcinoid tumor and membranous glomerulonephritis: coincidence or malignancy
      associated glomerulonephritis?
AB  - Membranous glomerulonephritis is known to be associated with malignancies. A 43
      year-old man with a history of chronic renal insufficiency secondary to 20-year
      old membranous glomerulonephritis was operated on for an infrarenal aneurysm.
      During surgical intervention, multiple nodular liver lesions were detected.
      Histologic examination of these lesions showed metastases of a carcinoid tumor.
      Despite extensive examination, the primary tumor site could not be detected. The
      patient remained asymptomatic 3 years postoperatively without any treatment for
      carcinoid tumor. This clinical report is the second case of a membranous
      glomerulonephritis associated with a carcinoid tumor. Whether the association is
      merely a coincidence or a real malignancy-related glomerulopathy remains unclear.
      Because survival of 23 years after the onset of symptoms of carcinoid tumor has
      occurred, it is possible that our patient already had an asymptomatic carcinoid
      tumor at the time the diagnosis of membranous glomerulonephritis was made.
      Comparison with other paraneoplastic glomerulonephritis as well as diagnosis of a
      carcinoid tumor in renal insufficiency are discussed.

PMID- 11837807
TI  - Severe hyponatremia as the presenting feature of clinically non-functional
      pituitary adenoma with hypopituitarism.
AB  - Hyponatremia can result from a wide range of causes. While hyponatremia is known
      to occur in patients with hypopituitarism, severe hyponatremia occurring as the
      presenting feature of hypopituitarism is very rare. We present two cases in which
      severe hyponatremia developed with weakness, light-headedness and seizure. The
      hyponatremia in these 2 cases mimicked the laboratory diagnostic criteria of a
      syndrome of inappropriate secretion of antidiuretic hormone (SIADH). However, the
      hormone studies displayed hypopituitarism. Hyponatremia was completely corrected
      after administering a supplement of prednisolone and L-thyroxine. Computerized
      tomography of the brain revealed an adenoma of the pituitary gland. These two
      cases illustrate that severe hyponatremia may be the presenting feature of
      clinically non-functional pituitary adenoma with hypopituitarism, which should be
      kept in mind in the differential diagnosis of hyponatremia mimicking SIADH.

PMID- 11837808
TI  - Hypokalemic rhabdomyolysis aggravated by diuretics complicating Conn's syndrome
      without acute renal failure.

PMID- 11837809
TI  - Biological evolution of renal osteodystrophy after decreasing dialysate calcium
      from 1.75 to 1.6 mmol/l.

PMID- 11837810
TI  - Spurious hyperchloremia and cerebellar ataxia: clue to suggest chronic
      bromvalerylurea intoxication.

PMID- 11837811
TI  - Tendinopathy of tendo achillis.

PMID- 11837812
TI  - Ultrasound diagnosis of shoulder congruity in chronic obstetric brachial plexus
      palsy.
AB  - Ultrasound (US) was used to determine the congruity of the shoulder in 22
      children with a deformity of the shoulder secondary to chronic obstetric brachial
      plexus palsy. There were 11 boys and 11 girls with a mean age of 4.75 years (0.83
      to 13.92). The shoulder was scanned in the axial plane using a posterior approach
      with the arm internally rotated. The humeral head was classified as being either
      congruent or incongruent. The US appearance was compared with that on clinical
      examination and related to the intraoperative findings. All 17 shoulders
      diagnosed as incongruent on US were found to be incongruent at operation, whereas
      three diagnosed as congruent by US were found to be incongruent at operation. The
      diagnostic accuracy of US for the identification of shoulder incongruity was 82%
      when compared with the findings at surgery. US is a valuable, but not infallible
      tool, for the detection of incongruity of the shoulder.

PMID- 11837813
TI  - Unilateral limitation of abduction of the hip. A valuable clinical sign for DDH?
AB  - Between 1992 and 1997, we undertook a prospective, targeted clinical and
      ultrasonographic hip screening programme to assess the relationship between
      ultrasonographic abnormalities of the hip and clinical limitation of hip
      abduction. A total of 5.9% (2 of 34) of neonatal dislocatable hips and 87.5% (7
      of 8) of 'late' dislocated hips seen after the age of six months, presented with
      unilateral limitation of hip abduction. All major (Graf type III) and 44.5% of
      minor (Graf type II) dysplastic hips presented with this sign. Statistically,
      bilateral limitation of hip abduction was not a useful clinical indicator of
      underlying hip abnormality because of its poor sensitivity, but unilateral
      limitation of abduction of the hip was a highly specific (90%) and reasonably
      sensitive sign (70%). It was more sensitive than the neonatal Ortolani manoeuvre,
      which has been considered to be the method of choice. It was, however, not
      sensitive enough to be of value as a routine screening test in developmental
      dysplasia of the hip. We consider unilateral limitation of hip abduction to be an
      important clinical sign and its presence in an infant over the age of three to
      four months makes further investigation essential.

PMID- 11837814
TI  - Displaced fractures of the hip in children. Management by early operation and
      immobilisation in a hip spica cast.
AB  - Fractures of the hip in children have been associated with a very high rate of
      serious complications including avascular necrosis (up to 47%) and coxa vara (up
      to 32%). Over a period of 20 years, we have treated displaced fractures by early
      anatomical reduction, internal fixation and immobilisation in a spica cast to try
      to reduce these complications. We have reviewed 18 patients who had a displaced
      non-pathological fracture of the hip when under 16 years of age. Their mean age
      at the time of the injury was eight years (2 to 13). They returned for
      examination and radiography at a mean follow-up of eight years (2 to 17). Each
      patient had been treated by early (" 24 hours) closed or open reduction with
      internal fixation and 16 had immobilisation in a spica cast. By Delbet's
      classification, there was one type-I, eight type-II, eight type-III, and one type
      IV fractures. There were no complications in 15 patients. Avascular necrosis
      occurred in one patient (type-III), nonunion in one (type-II, one of the two
      patients who did not have a cast) and premature physeal closure in one (type-I).
      There were no cases of infection or complications as a result of the cast. Our
      treatment of displaced hip fractures in children by early reduction, internal
      fixation, and immobilisation in a spica cast gave reduced rates of complications
      compared with that of large published series in the literature.

PMID- 11837815
TI  - Extensor retinaculum syndrome of the ankle after injury to the distal tibial
      physis.
AB  - We describe six patients aged from 10 to 15 years who, after injury to the distal
      tibial physis, presented with the following clinical findings: 1) severe pain and
      swelling of the ankle; 2) hypoaesthesia or anaesthesia in the web space of the
      great toe; 3) weakness of extensor hallucis longus and extensor digitorum
      communis; and 4) pain on passive flexion of the toes, especially the great toe.
      In four patients, the fractures were not reduced for more than 24 hours. The
      intramuscular pressure beneath the superior extensor retinaculum of the ankle was
      greater than 40 mmHg in all cases (40 to 130 mmHg), and less than 20 mmHg in the
      anterior compartment. Treatment consisted of release of the superior extensor
      retinaculum and stabilisation of the fracture. All patients had prompt relief of
      pain and improved strength and sensation within 24 hours, although two had some
      residual numbness in the web space of the great toe.

PMID- 11837816
TI  - Transepiphyseal fracture of the femoral neck with dislocation of the femoral head
      and fracture of the posterior column of the acetabulum in a child.
AB  - We describe a 15-year-old boy with a posterior dislocation of the hip, fracture
      of the posterior column of the acetabulum and separation of the femoral capital
      epiphysis. To our knowledge no previous case in a child has been reported. Such
      high-energy injuries are extremely rare, and a poor outcome is expected. We
      advocate early referral to a specialised tertiary centre, and the use of a
      modification of Delbet's classification to reflect the complexity and
      displacement which may occur with this injury.

PMID- 11837817
TI  - Human skeletal muscle cells in ex vivo gene therapy to deliver bone morphogenetic
      protein-2.
AB  - We have examined whether primary human muscle-derived cells can be used in ex
      vivo gene therapy to deliver BMP-2 and to produce bone in vivo. Two in vitro
      experiments and one in vivo experiment were used to determine the osteocompetence
      and BMP-2 secretion capacity of cells isolated from human skeletal muscle. We
      isolated five different populations of primary muscle cells from human skeletal
      muscle in three patients. In the first in vitro experiment, production of
      alkaline phosphatase by the cells in response to stimulation by rhBMP-2 was
      measured and used as an indicator of cellular osteocompetence. In the second,
      secretion of BMP-2 was measured after the cell populations had been transduced by
      an adenovirus encoding for BMP-2. In the in vivo experiment, the cells were
      cotransduced with a retrovirus encoding for a nuclear localised beta
      galactosidase gene and an adenovirus encoding for BMP-2. The cotransduced cells
      were then injected into the hind limbs of severe combined immune-deficient (SCID)
      mice and analysed radiographically and histologically. The nuclear localised beta
      galactosidase gene allowed identification of the injected cells in histological
      specimens. In the first in vitro experiment, the five different cell populations
      all responded to in vitro stimulation of rhBMP-2 by producing higher levels of
      alkaline phosphatase when compared with non-stimulated cells. In the second, the
      five different cell populations were all successfully transduced by an adenovirus
      to express and secrete BMP-2. The cells secreted between 444 and 2551 ng of BMP-2
      over three days. In the in vivo experiment, injection of the transduced cells
      into the hind-limb musculature of SCID mice resulted in the formation of ectopic
      bone at 1, 2, 3 and 4 weeks after injection. Retroviral labelling of the cell
      nuclei showed labelled human muscle-derived cells occupying locations of
      osteoblasts in the ectopic bone, further supporting their osteocompetence. Cells
      from human skeletal muscle, because of their availability to orthopaedic
      surgeons, their osteocompetence, and their ability to express BMP-2 after genetic
      engineering, are an attractive cell population for use in BMP-2 gene therapy
      approaches.

PMID- 11837818
TI  - Adverse tissue reactions to wear particles from Co-alloy articulations, increased
      by alumina-blasting particle contamination from cementless Ti-based total hip
      implants. A report of seven revisions with early failure.
AB  - We revised seven alumina-blasted cementless hip prostheses (Ti-alloy stems, cp Ti
      threaded sockets) with low- or high-carbon Co-alloy bearings at a mean of 20.1
      months after implantation because of pain and loosening. Histological examination
      of the retrieved periprosthetic tissues from two cases in which the implant was
      stable and three in which the socket was loose showed macrophages with basophilic
      granules containing metal and alumina wear particles and lymph-cell infiltrates.
      In one of the two cases of stem loosening the thickened neocapsule also contained
      definite lymphatic follicles and gross lymphocyte/plasma-cell infiltrates.
      Spectrometric determination of the concentration of elements in periprosthetic
      tissues from six cases was compared with that of joint capsules from five control
      patients undergoing primary hip surgery. In the revisions the mean concentration
      of implant-relevant elements was 693.85 microg/g dry tissue. In addition to Cr
      (15.2%), Co (4.3%), and Ti (10.3%), Al was predominant (68.1%) and all
      concentrations were significantly higher (p < 0.001) than those in the control
      tissues. The annual rates of linear wear were calculated for six implants. The
      mean value was 11.1 microm (heads 6.25 microm, inserts 4.82 microm). SEM/EDXA
      showed numerous fine scratches and deep furrows containing alumina particles in
      loosened sockets, and stems showed contamination with adhering or impacted
      alumina particles of between 2 and 50 microm in size.

PMID- 11837819
TI  - Drilling efficiency and temperature elevation of three types of Kirschner-wire
      point.
AB  - An innovative Kirschner (K-) wire point was developed and compared in fresh pig
      femora in terms of drilling efficiency and temperature elevation with the trochar
      and diamond points currently used in clinical practice. The tips of thermal
      couples were machined to the defined geometry and the temperature measured during
      drilling. Using the same drill speed (rev/min) and feed rate, the new K-wire
      point produced the lowest thrust force and torque as measured by a Kistler
      dynamometer. Drill point temperatures were highest with the trochar geometry (129
      +/- 6 degrees C), followed by the diamond (98 +/- 7 degrees C). The lowest
      temperatures were recorded with the Medin K-wire (66 +/- 2 degrees C). On
      repeated drilling it could be used for up to 30 holes before reaching the less
      satisfactory drill performance of the diamond tip. The new K-wire provides a
      better alternative as it requires less effort for insertion, generates less heat
      and may be re-used.

PMID- 11837820
TI  - The blood supply of the posterior tibial tendon.
AB  - We studied the vascular pattern of human posterior tibial tendons by injection
      techniques and immunohistochemically using antibodies against laminin. The
      intravascular volume of the posterior tibial tendon was determined using a new
      method of injection of a solution of 99mTc and gelatin ink into the lower legs of
      cadavers. Three segments of 1 cm length from different regions of the human
      posterior tibial tendon were measured using a gamma well counter. The main blood
      supply arises from the posterior tibial artery. Blood vessels enter the paratenon
      of the posterior tibial tendon via a mesotenon from the posterior aspect. From
      the paratenon, the blood vessels penetrate the posterior tibial tendon and
      anastomose with a longitudinally orientated intratendinous network. The number of
      vessels in the substance of the tendon is consistently less than that in the
      surrounding paratenon. The distribution of blood vessels within the posterior
      tibial tendon is not homogeneous. In the retromalleolar region the intravascular
      volume was significantly reduced with a mean value of 15 microl/g of tendon
      tissue. There was no significant difference between the mean intravascular
      volumes of the proximal and distal areas (distal, 27.7 microl/g tendon tissue;
      proximal, 30 microl/g tendon tissue). The immunohistochemical investigation
      showed that there was no immunostaining for laminin in the anterior part of the
      tendon in the region where it passes behind the medial malleolus. This region is
      avascular. The most frequent site of rupture of the posterior tibial tendon is in
      the region behind the medial malleolus. A potential endogenous risk factor may be
      the limited healing potential of avascular tissue.

PMID- 11837821
TI  - Long-term results of retention of the posterior cruciate ligament in total knee
      replacement.

PMID- 11837822
TI  - Strain distribution in the proximal human femur.

PMID- 11837823
TI  - Ilizarov external fixation for severely comminuted supracondylar and
      intercondylar fractures of the distal femur.

PMID- 11837824
TI  - At the crossroads--neonatal detection of developmental dysplasia of the hip.

PMID- 11837825
TI  - Interobserver and intraobserver variation in the assessment of the healing of
      tibial fractures after intramedullary fixation.
AB  - The reliability of the radiological assessment of the healing of tibial fractures
      remains undetermined. We examined the inter- and intraobserver agreement of the
      healing of such fractures among four orthopaedic trauma surgeons who, on two
      separate occasions eight weeks apart, independently assessed the radiographs of
      30 patients with fractures of the tibial shaft which had been treated by
      intramedullary fixation. The radiographs were selected from a database to
      represent fractures at various stages of healing. For each radiograph, the
      surgeon scored the degree of union, quantified the number of cortices bridged by
      callus or with a visible fracture line, described the extent and quality of the
      callus, and provided an overall rating of healing. The interobserver chance
      corrected agreement using a quadratically weighted kappa (kappa) statistic in
      which values of 0.61 to 0.80 represented substantial agreement were as follows:
      radiological union scale (kappa= 0.60); number of cortices bridged by callus
      (kappa = 0.75); number of cortices with a visible fracture line (kappa= 0.70);
      the extent of the callus (kappa = 0.57); and general impression of fracture
      healing (kappa = 0.67). The intraobserver agreement of the overall impression of
      healing (kappa = 0.89) and the number of cortices bridged by callus (kappa =
      0.82) or with a visible fracture line (kappa = 0.83) was almost perfect. There
      are no validated scales which allow surgeons to grade fracture healing
      radiologically. Among those examined, the number of cortices bridged by bone
      appears to be a reliable, and easily measured radiological variable to assess the
      healing of fractures after intramedullary fixation.

PMID- 11837826
TI  - The Gotfried percutaneous compression plate compared with the conventional
      classic hip screw for the fixation of intertrochanteric fractures of the hip.
AB  - We performed a randomised, prospective trial in 111 patients with
      intertrochanteric fractures of the hip comparing the use of the Gotfried
      percutaneous compression plate (PCCP) with that of the classic hip screw (CHS).
      Blood loss and transfusion requirement were less in the PCCP group but the
      operating time was significantly longer. The complication rate after operation
      was similar in both groups, and at a minimum follow-up of six months there was no
      difference in the rates of fracture healing or implant failure. The PCCP gives
      results which are similar to those obtained with a conventional device. Its
      suggested advantages seem to be theoretical rather than practical and, being a
      fixed-angle implant, it is not universally applicable.

PMID- 11837827
TI  - The external fixator compared with the sliding hip screw for pertrochanteric
      fractures of the femur.
AB  - In a prospective, randomised study we have compared the pertrochanteric external
      fixator (PF) with the sliding hip screw (SHS) in 100 consecutive patients who
      were allocated randomly to the two methods of treatment. Details of the patients
      and the patterns of fracture were similar in both groups. Follow-up was for six
      months. Use of the PF was associated with significantly less blood loss, a
      shorter operating time, reduced postoperative pain, shorter hospitalisation (p <
      0.001), earlier mobilisation (p < 0.001) and a reduced rate of mechanical
      complications (p < 0.01). Superficial infection was significantly more common
      with the PF (p < 0.01), but without long-term adverse consequences. There were no
      differences in the healing of the fracture, mortality or final functional
      outcome. Our results indicate that the external fixator is an effective and safe
      device for treating pertrochanteric fractures and should be considered as a
      useful alternative to conventional fixation with the sliding hip screw.

PMID- 11837828
TI  - Modification of the Nicoll bone-grafting technique for nonunion of the radius
      and/or ulna.
AB  - We treated 19 patients with established nonunion of the radius and/or ulna by the
      excision of avascular bone and the grafting of blocks of corticocancellous bone
      from the iliac crest, augmented by rigid plate fixation under compression. This
      allowed early mobilisation, and bony union was achieved between three and 24
      months after operation in all but one of the patients. The single failure was
      attributed to the excessive length of the defect (100 mm) and inadequate
      fixation.

PMID- 11837829
TI  - Repeat tears of repaired menisci after arthroscopic confirmation of healing.
AB  - We undertook 114 arthroscopic meniscal repairs in 111 patients and subsequently
      carried out second-look arthroscopy to confirm meniscal healing at a mean of 13
      months after repair. Stable healing at the repaired site was seen in 90. Of
      these, however, 13 had another arthroscopy later for a further tear. The mean
      period between the repair and the observation of a repeat tear was 48 months. Of
      the 13 patients, 11 had returned to high activity levels (International Knee
      Documentation Committee level I or II) after the repair. An attempt should be
      made to preserve meniscal function by repairing tears, but even after
      arthroscopic confirmation of stable healing repaired menisci may tear again. The
      long-term rate of healing may not be as high as is currently reported. Second
      look arthroscopy cannot predict late meniscal failure and may not be justified as
      a method of assessment for meniscal healing. Young patients engaged in arduous
      sporting activities should be reviewed regularly even after arthroscopic
      confirmation of healing.

PMID- 11837830
TI  - The natural history and treatment of rupture of the anterior cruciate ligament in
      children and adolescents. A prospective review.
AB  - A total of 60 children and adolescents with rupture of the anterior cruciate
      ligament (ACL) was seen between 1980 and 1990. Observation of the 23 patients who
      were treated conservatively revealed that the natural history of the injury
      resulted in severe instability and poor function of the knee. Associated meniscal
      tears were present in 15 knees. Three osteochondral fractures occurred and
      osteoarthritic changes developed in ten knees. In 1990 therefore we introduced
      reconstruction of the ACL with a four-strand hamstring graft using an anatomical
      placement with transphyseal tunnels and anchorage well away from the growth
      plate. Over a period of nine years, 47 knees underwent reconstruction. The mean
      follow-up was 49 months (12 to 96). No child suffered physeal damage or leg
      length discrepancy. The results were satisfactory in 77% and there was little
      difference between patients treated before the adolescent growth spurt and those
      treated during or after this time. These results, however, were not as good as
      those seen in adults during the same period.

PMID- 11837831
TI  - Observer reliability in the arthroscopic classification of osteoarthritis of the
      knee.
AB  - We studied 19 videotaped knee arthroscopies in 19 patients with mild to moderate
      osteoarthritis (OA) of the knee in order to compare the intraobserver and
      interobserver reliability and the patterns of disagreement between four
      orthopaedic surgeons. The classifications of OA of Collins, Outerbridge and the
      French Society of Arthroscopy were used. Intraobserver and interobserver
      agreements using kappa measures were 0.42 to 0.66 and 0.43 to 0.49, respectively.
      Only 6% to 8% of paired intraobserver classifications differed by more than one
      category. Observer-specific disagreement was evident both within and between
      observers. A small, but significant, occasional variation was also seen. Although
      reliability may improve by an analysis of disagreement, it appears that the
      arthroscopic grading of early osteoarthritic lesions is inexact.

PMID- 11837832
TI  - Fluoroscopic analysis of the kinematics of deep flexion in total knee
      arthroplasty. Influence of posterior condylar offset.
AB  - Our purpose was to determine the mechanism which allows the maximum knee flexion
      in vivo after a posterior-cruciate-ligament (PCL)-retaining total knee
      arthroplasty. Using three-dimensional computer-aided design videofluoroscopy of
      deep squatting in 29 patients, we determined that in 72% of knees, direct
      impingement of the tibial insert posteriorly against the back of the femur was
      the factor responsible for blocking further flexion. In view of this finding we
      defined a new parameter termed the 'posterior condylar offset'. In 150
      consecutive arthroplasties of the knee, the magnitude of posterior condylar
      offset was found to correlate with the final range of flexion.

PMID- 11837833
TI  - Calcaneal osteotomy and transfer of the tendon of flexor digitorum longus for
      stage-II dysfunction of tibialis posterior. Three- to five-year results.
AB  - The treatment of acquired flat foot secondary to dysfunction of the posterior
      tibial tendon (PTT) of stage II, as classified by Johnson and Strom, remains
      controversial. Joint sparing and soft-tissue reconstructive procedures give good
      early results, but few studies describe those in the medium-term. We studied
      prospectively the outcome of surgery in 51 patients with classical stage-II
      dysfunction of the PTT treated by a medial displacement calcaneal osteotomy and
      transfer of the tendon of flexor digitorum longus. We reviewed 44 patients with a
      mean follow-up of 51 months (38 to 62). The mean American Orthopaedic Foot and
      Ankle Society ankle/hindfoot rating scale improved from 48.8 before operation to
      88.5 at follow-up. The operation failed in two patients who later had a
      calcaneocuboid fusion. The outcome in 43 patients was rated as good to excellent
      for pain and function, and in 36 good to excellent for alignment. There were no
      poor results.

PMID- 11837834
TI  - Rotational acetabular osteotomy for acetabular dysplasia. A follow-up for more
      than ten years.
AB  - Between 1986 and 1990, we carried out 55 rotational acetabular osteotomies in 54
      patients with acetabular dysplasia. Five hips were lost to follow-up. Of the 50
      remaining, the degenerative changes were classified according to the criteria of
      Tonnis as grade 0 in 23, grade 1 in 16 and grade 2 in 11. The mean age of the
      three men and 46 women at the time of operation was 31.8 years (13 to 53). The
      mean follow-up was 137 months (120 to 174). At the most recent follow-up, 48
      patients had satisfactory relief from pain. There was a slight decrease in the
      range of movement, particularly of flexion, in 18 hips. Radiologically, all
      osteotomies had united satisfactorily. There was radiological evidence of
      improvement in degenerative changes in 13 hips (5 grade 1 and 8 grade 2). Ten
      deteriorated (5 grade 0, 3 grade 1, and 2 grade 2) and one required total hip
      arthroplasty ten years after osteotomy. The osteoarthritis in the two hips with
      an associated valgus osteotomy progressed. The changes in radiological indices
      such as the centre-edge angle, acetabular femoral head index, acetabular root
      obliquity and horizontal or vertical displacement of the femoral head showed no
      statistical difference (unpaired Student's t-test) between the patients with
      radiological progression and those with and without improvement.

PMID- 11837835
TI  - Early lesions of the labrum and acetabular cartilage in osteonecrosis of the
      femoral head.
AB  - Osteonecrosis of the femoral head can be caused by a variety of disorders and
      affects the relatively young patient. Most studies have concentrated on the
      femoral changes; the sites of early lesions of the labrum and acetabular
      cartilage have not been recorded. We studied 17 hips with osteonecrosis and a
      wide congruent joint space on radiographs and by direct inspection of the femoral
      head, labrum and acetabular cartilage during surgery. All of the femoral heads
      had some anterosuperior flattening which reduced the head-neck ratio in this
      area. A consistent pattern of damage to the labrum and the acetabular cartilage
      was seen in all hips. Intraoperatively, impingement and the cam-effect with its
      spatial correlation with lesions of the labrum and acetabular cartilage were
      observed. These findings could be helpful when undertaking conservative surgery
      for osteonecrosis, since the recognition of early radiologically undetectable
      acetabular lesions may require modification of the surgical technique.

PMID- 11837836
TI  - The use of vancomycin-impregnated cement beads in the management of infection of
      prosthetic joints.
AB  - Although the incidence of infection associated with hip and knee prostheses is
      low, with the increasing number of arthroplasties being carried out, the total
      number of such cases is increasing. The pattern of infecting organisms after
      total joint arthroplasty has changed and gentamicin-resistant organisms are
      becoming increasingly common. In conjunction with surgical debridement,
      vancomycin added to a bone-cement carrier can be very effective in the treatment
      of infection caused by such organisms. We report the results of its use in proven
      deep infection in 26 hip and seven knee arthroplasties. After a mean follow-up of
      67 months, 32 patients remained clinically and radiologically free from
      infection. There was one recurrence and positive second-stage cultures of
      uncertain significance in three other patients. Vancomycin is potentially very
      useful in the management of deep infection after arthroplasty.

PMID- 11837837
TI  - Normal anteroposterior laxity of the radiocarpal and midcarpal joints.
AB  - The patterns of laxity of normal wrists subjected to dorsal and volar stresses
      were analysed. Dorsal and volar displacement tests were carried out on both
      wrists of 50 subjects under image-intensifier control. Lateral projections in
      neutral, and dorsal and volar stress positions were taken to analyse the
      behaviour of the carpal bones. Varying degrees of capitolunate subluxation under
      dorsal and volar stress were noted. Dorsal displacement of the capitate appeared
      to be more prominent than volar displacement. The lunate either extended or
      subluxed dorsally in response to a dorsal stress, suggesting a different pattern
      of laxity for the radiolunate joint. These observations provide a baseline for
      the interpretation of dorsal and volar stress views in the symptomatic wrist.

PMID- 11837838
TI  - Patterns of loosening of the glenoid component.
AB  - The incidence of loosening of a cemented glenoid component in total shoulder
      arthroplasty, detected by means of radiolucent lines or positional shift of the
      component on true anteroposterior radiographs, has been reported to be between 0%
      and 44%. Radiolucent lines are, however, difficult to detect and to interpret
      because of the mobility of the shoulder girdle and the obliquity of the glenoid
      which hinder standardisation of radiographs. We examined radiolucencies around
      cemented glenoid components in 48 patients, with a mean follow-up of 5.3 years,
      and found progressive changes to be present predominantly at the inferior pole of
      the component. This may hold a clue for the mechanism of loosening of this
      implant. In five patients we performed an additional analysis of loosening of the
      glenoid component using digital roentgen stereophotogrammetric analysis (RSA).
      After three years, three of the five implants had loosened (migration 1.2 to 5.5
      mm). In only one, with gross loosening, were the radiological signs consistent
      with the RSA findings. When traditional radiographs are used for assessment, the
      rate of early loosening is underestimated. We recommend that RSA be used for
      this.

PMID- 11837839
TI  - Osteosarcoma of the limb. Amputation or limb salvage in patients treated by
      neoadjuvant chemotherapy.

PMID- 11837840
TI  - Fusion for spinal stenosis: a personal view.

PMID- 11837841
TI  - Risk factors for survival and local control in chondrosarcoma of bone.
AB  - We studied 153 patients with non-metastatic chondrosarcoma of bone to determine
      the risk factors for survival and local tumour control. The minimum follow-up was
      for five years; 52 patients had axial and 101 appendicular tumours. Surgical
      treatment was by amputation in 27 and limb-preserving surgery in 126. The
      cumulative rate of survival of all patients, at 10 and 15 years, was 70% and 63%,
      respectively; 40 patients developed a local recurrence between 3 and 87 months
      after surgery and 49 developed metastases. Local recurrence was associated with
      poor survival in patients with concomitant metastases but not in those without.
      On multivariate analysis independent risk factors for rates of survival include
      extracompartmental spread, development of local recurrence and high histological
      grade. Independent risk factors for local recurrence include inadequate surgical
      margins and tumour size greater than 10 cm. Location within the body, the type of
      surgery and the duration of symptoms are of no prognostic significance. Surgical
      excision with an oncologically wide margin provides the best prospect both for
      cure and local control in these patients.

PMID- 11837842
TI  - Environment, sustainability and health: the learning curve steepens.

PMID- 11837844
TI  - Bullfighting in Barcelona.

PMID- 11837843
TI  - Bridging the divide: global inequities in access to HIV/AIDS therapy.

PMID- 11837845
TI  - Malaria, malnutrition and MSF. Medecins Sans Frontieres.
AB  - This is a personal account of my brief time in Burundi as a volunteer doctor with
      Medecins Sans Frontieres (MSF) at the beginning of 2001. Burundi is a small
      nation in central Africa (bounded by the Democratic Republic of Congo, Rwanda and
      Tanzania) which has suffered from problems between the Hutu and Tutsi "ethnic
      groups", similar to those for which Rwanda is better known. Unlike Rwanda, the
      war between government troops and rebel forces continues in Burundi. MSF has been
      in Burundi since 1992, providing basic healthcare, nutrition programs, surgical
      services and epidemiological intervention. In late 2000, a malaria epidemic began
      in Burundi's highland regions where transmission is normally low, and thus the
      population largely not immune. Malnutrition rates also increased and MSF rapidly
      expanded its usual program in an attempt to control these new health problems.

PMID- 11837846
TI  - Arrival and departure.
AB  - As the small jet circled the dirt landing strip, I felt apprehensive. The
      briefing in Nairobi had been very detailed but hadn't really allayed my fears. I
      struggled with my emotions and too many unanswerable questions. Why was I going
      to Somalia in the middle of a civil war, a war about which I knew so very little?
      What were the risks and what did I hope to achieve?

PMID- 11837847
TI  - The place of infamy.

PMID- 11837848
TI  - Death in Antarctica.
AB  - Antarctic tourism is flourishing, but Antarctic cruises are often more physically
      demanding than typical "tropical" cruises. An 82-year-old Antarctic tourist died
      of probable septic shock secondary to lower respiratory tract infection six days
      after sustaining a suspected vertebral fracture in a minor fall from an
      inflatable boat. This case highlights the need for Antarctic cruise ships to be
      equipped to provide life support and for better screening and education of
      prospective Antarctic tourists.

PMID- 11837849
TI  - So this is Christmas.

PMID- 11837850
TI  - Goanna oil.

PMID- 11837851
TI  - An unusual cause of immobility.

PMID- 11837852
TI  - Asylum seekers in Australia.

PMID- 11837853
TI  - The health needs of asylum seekers living in the community.
AB  - Asylum seekers living in the Australian community, and awaiting the outcome of
      applications for protection visas, may require medical treatment for a range of
      illnesses, and are likely to have psychological or musculoskeletal problems as a
      consequence of traumatic experiences in their own countries. Many require
      specialist treatment. Some asylum seekers living in the community are denied
      access to Medicare and can not afford basic medical treatment. This creates
      suffering in the short term and complications in the long term. Healthcare
      professionals have an ethical responsibility to provide basic medical care for
      asylum seekers in Australia.

PMID- 11837854
TI  - Psychological disturbances in asylum seekers held in long term detention: a
      participant-observer account.
AB  - The process of applying for refugee status in Australia is complex, lengthy and
      often poorly understood by asylum seekers. The psychological reaction patterns of
      detainees whose claims for asylum are unsuccessful are characterised by stages of
      increasing depression, punctuated by periods of protest, as feelings of injustice
      overwhelm them. These reactions have a marked secondary impact on their children
      in detention. The prolonged detention of asylum seekers appears to cause serious
      psychological harm. Even if many of those who spend long periods of time are not
      deemed to have proven their refugee claims, this administrative decision should
      not be grounds for inflicting grave ongoing psychological injury on the
      applicants.

PMID- 11837855
TI  - The mental health implications of detaining asylum seekers.
AB  - The possible mental health impact on asylum seekers of Australia's policy of
      mandatory detention is an issue of special relevance to health professionals and
      the public. Independent commissions of inquiry in Australia have found varying
      degrees of mental distress to be common in detained asylum seekers. Research
      studies in Australia and elsewhere suggest that detained asylum seekers may have
      suffered greater levels of past trauma than other refugees, and this may
      contribute to their mental health problems, with their detention providing a
      retraumatising environment. Studies are urgently required to examine the mental
      health consequences of detention, and to determine the effect of detention on
      acculturation and adaptation for asylum seekers subsequently released into the
      community.

PMID- 11837856
TI  - Screening for conditions of public health importance in people arriving in
      Australia by boat without authority.
AB  - OBJECTIVE: To determine the prevalence of tuberculosis, hepatitis B carriage and
      markers of hepatitis C and HIV infection in people detained in immigration
      reception and processing centres in Australia. DESIGN AND SETTING: Eighteen-month
      survey of medical conditions of public health importance in people detained at
      the immigration reception and processing centres at Curtin and Port Hedland in
      Western Australia and Woomera in South Australia. PARTICIPANTS: 7000 detainees
      (5742 adults and 1258 children and teenagers aged < 18 years) between 1 January
      2000 and 30 June 2001. MAIN OUTCOME MEASURES: People treated for active
      tuberculosis; issuing of health undertakings to report to a chest clinic for
      follow-up of inactive tuberculosis; and confirmation of hepatitis B carrier
      status or hepatitis C or HIV infection. RESULTS: Eleven people required treatment
      for tuberculosis (in nine the diagnosis was confirmed bacteriologically),
      representing a prevalence of 157 cases per 100,000 population. This rate is much
      higher than the incidence in Australia in 1998 of 4.93 cases per 100,000
      population, but comparable with rates in the source countries. Health
      undertakings were issued to 973 people (13.9%). Of these, 682 (70.1%) were for
      inactive tuberculosis (26 in association with hepatitis B carriage or hepatitis C
      infection); and 156, 58 and two health undertakings were for hepatitis B
      carriage, and hepatitis C and HIV infection, respectively. CONCLUSIONS: The
      health-screening program at immigration reception and processing centres detects
      significant numbers of conditions of public health importance, enabling treatment
      and surveillance to the benefit of the people detained and the Australian
      community.

PMID- 11837857
TI  - Preventing children drowning in Australia.

PMID- 11837858
TI  - Drowning and near-drowning in Northern Territory children.
AB  - OBJECTIVE: To compare incidences of drowing for children in the Northern
      Territory (NT) with those in Queensland and the rest of Australia. DESIGN:
      Descriptive, retrospective, population-based analysis of death and
      hospitalisation data for drowning and near-drowning. SETTING AND PARTICIPANTS:
      Children aged 0-14 years resident in Australia from 1983 to 1998. MAIN OUTCOME
      MEASURES: Age-standardised average annual incidence of drowning (1983-1998) and
      near-drowning (1994-1997) in children aged 0-4 and 5-14 years in the NT,
      Queensland and the rest of Australia. RESULTS: The average annual incidence of
      drowning and near-drowning from 1994 to 1997 for children aged 0-4 years in the
      NT (67.82 per 100,000) was significantly higher than for Australia (24.45 per
      100,000) (incident rate ratio [IRR], 2.77; 95% CI, 1.40-4.91) and for Queensland
      (32.55 per 100,000) (IRR, 2.13; 95% CI, 1.05-3.94). The proportion of children
      aged 0-4 years drowning or near-drowning in swimming pools from 1994 to 1997 was
      also significantly higher in the NT (83%) than Australia (64%) (difference, 0.19;
      95% CI, 0.086-0.30) and Queensland (65%) (difference, 0.18; 95% Cl, 0.069-0.29).
      From 1983 to 1998, the incidence of drowning in NT children aged 0-4 years
      increased by 0.4% per year (IRR, 1.004; 95% Cl, 0.994-1.070), compared with a
      5.0% reduction per year (IRR, 0.950; 95% Cl, 0.937-0.963) in Australian children.
      CONCLUSIONS: The incidences of drowning and near-drowning in the NT are higher
      than in the rest of Australia and show no significant decrease. The NT should
      improve its measures for prevention of childhood drowning.

PMID- 11837859
TI  - A snip in time saves nine.

PMID- 11837860
TI  - Horse-related injuries in children.
AB  - OBJECTIVES: To identify the frequency, spectrum and outcome of horse-related
      injuries in children. DESIGN AND SETTING: Retrospective case series of horse
      related injuries in children admitted to the Children's Hospital at Westmead
      (CHW) from January 1988 to December 1999, the John Hunter Children's Hospital
      (JHCH) from January 1991 to December 1997 and deaths reported to the New South
      Wales Paediatric Trauma Death (NPTD) Registry from January 1988 to December 1999.
      MAIN OUTCOME MEASURES: Circumstances of injury; helmet use; adult supervision;
      type and number of injuries identified. RESULTS: 232 children were admitted with
      horse-related trauma, 97 to the CHW over 12 years and 135 to JHCH over seven
      years, with one death at each hospital. There were six deaths reported to the
      NPTD Registry over 12 years. The median age was 11 years (range, 1-17). Girls
      accounted for 65% of those injured and 75% of children were injured while riding.
      Falls caused the injury in 76.3% of cases. Head and upper-limb trauma accounted
      for 216 of the injuries (73%). Five out of six children with severe head injuries
      died. In the CHW group, helmet use was documented in only 24 riders (38%) and
      adult supervision in 22 (22.9%). CONCLUSIONS: Horse-related trauma accounts for a
      considerable number of deaths and injuries in children in NSW. The use of a
      Standards-approved helmet for riding or horse-related activities might have
      decreased the severity of head injuries.

PMID- 11837861
TI  - Organised curiosity.

PMID- 11837862
TI  - The Menzies Centre for Population Health Research.

PMID- 11837865
TI  - Not murder most foul.

PMID- 11837866
TI  - Dolphin deaths: forensic investigations.

PMID- 11837867
TI  - Trial of a trial by media.

PMID- 11837869
TI  - Media milking of sacred cows: a heart-stopping tale.

PMID- 11837870
TI  - Clinical research in the emergency setting: the role of ethics committees.

PMID- 11837871
TI  - The epidemiology of dog walking: an unmet need for human and canine health.
AB  - OBJECTIVE: To describe the prevalence of dog walking in New South Wales, and to
      identify potential health gains if more dogs were walked. DESIGN: Cross-sectional
      analytical survey. SETTING AND PARTICIPANTS: 894 adults in NSW in 1998 (among the
      owners of approximately two million domestic dogs in NSW who were potential
      participants in dog-walking behaviours). INTERVENTIONS: None yet. MAIN OUTCOME
      MEASURES: Dog walking hours per week; other DogEpi concepts to illustrate the
      public health gains include the DAF (dog attributable fraction), and the BBR
      (benefits to bites ratio). RESULTS: The response rate to the survey was 74%. 46%
      of households in NSW had a dog and, overall, dog owners walked 18 minutes per
      week more than non-dog owners. However, more than half of dog owners did not walk
      their dogs, and were less likely than non-owners to meet recommended levels of
      physical activity sufficient for health benefits. If all dog owners walked their
      dogs, substantial disease prevention and healthcare cost savings of $175 million
      per year might accrue. CONCLUSIONS: There are potential benefits of dog walking
      for human health; currently, among dog owners, much of this benefit remains to be
      realised. There are also likely benefits for canine health. Dog walking should be
      promoted through national strategies recommending "Walkies for all by the year
      2010".

PMID- 11837872
TI  - Estimating historical changes in physical activity levels.
AB  - OBJECTIVE: To compare activity levels between a simulated "historical" lifestyle
      and a "modern" lifestyle to try to validate earlier estimates of secular changes
      in activity. DESIGN: Triaxial accelerometers (TRACMORs) were used to measure
      activity levels in a "historical" group of seven male actors who were paid to
      live like early Australian settlers at a theme park north of Sydney (eg,
      minimising the use of modern technology) for a week. Results were compared with
      those from a group of seven "modern" sedentary office workers. RESULTS: Activity
      levels were up to 2.3 times greater in the historical group than the modern
      group. Calculations based on body weight and energy expenditure suggest the
      difference is the equivalent of walking up to 16 km per day more in the past than
      today. CONCLUSIONS: These findings accord with two previous estimates of changes
      in daily activity levels over time and suggest that recent public health
      guidelines for increasing physical activity may be inadequate.

PMID- 11837873
TI  - Quick weight loss: sorting fad from fact.
AB  - This article reviews popular diets for their ability to produce effective weight
      loss. Most of the "evidence" for fad diets is based on anecdotal findings,
      theories and testimonials of short term results. The most prominent elements of
      fad diets are those of ritual and sacrifice. These diets offer quick and painless
      weight loss while allowing consumption of favourite or tasty foods, but place
      severe restrictions on certain other foods or food categories. Fad diets often
      work in the short term because they are low-kilojoule diets in disguise; that is,
      energy intake as a result of the diet is lower than the person's requirements.
      Successful long term weight loss depends on the consumption over a long period of
      time of less energy than is expended. The ideal approach is to increase physical
      activity while modifying eating behaviour to achieve a nutritionally balanced
      intake.

PMID- 11837874
TI  - Outbreak of caterpillar dermatitis caused by airborne hairs of the mistletoe
      browntail moth (Euproctis edwardsi).
AB  - Caterpillars may be an under-recognised cause of skin and eye reactions. We
      report a four-month outbreak of recurrent papulourticarial rash among staff and
      visitors at a community centre. Caterpillar of the mistletoe browntail moth The
      cause was eventually diagnosed as airborne hairs from (Euproctis edwardsi).
      caterpillars of the mistletoe browntail moth (Euproctis edwardsi), which infested
      a eucalypt tree growing in front of the centre. To our knowledge, this is the
      first clear case of airborne caterpillar hairs causing dermatitis in an indoor
      environment.

PMID- 11837876
TI  - Snakebite and antivenoms in the Asia-Pacific: wokabaut wantaim, raka hebou
      ("walking together").

PMID- 11837875
TI  - Fatal anaphylaxis following jack jumper ant sting in southern Tasmania.
AB  - The "jack jumper" ant (Myrmecia pilosula) is a major cause of anaphylaxis in
      Tasmania. We describe four deaths attributed to stings by this ant between 1980
      and 1999. All victims were men aged 40 years or over with significant
      comorbidities; two were taking angiotensin-converting enzyme inhibitors, which
      may increase risk of severe anaphylaxis. Three victims had known ant-sting
      allergy, but only one carried adrenaline, which he did not use. Another believed
      he was protected by previous attempts at hyposensitisation with whole ant-body
      extract. There is potential to prevent deaths by careful education of people with
      known allergy, prescribing of adrenaline for auto-injection and development of an
      effective hyposensitisation therapy.

PMID- 11837877
TI  - Prospective study of jellyfish stings from tropical Australia, including the
      major box jellyfish Chironex fleckeri.
AB  - OBJECTIVE: To determine the immediate and delayed effects of jellyfish stings,
      and correlate these with microscopic identification of jellyfish nematocysts.
      DESIGN: Prospective study of patients presenting with jellyfish stings.
      PARTICIPANTS AND SETTING: 40 people presenting with jellyfish stings to the
      emergency department of a teaching hospital in tropical Australia between 1
      August 1999 and 31 July 2000. MAIN OUTCOME MEASURES: Clinical diagnosis (sting by
      Chironex fleckeri, "Darwin carybdeid" or other jellyfish, or "Irukandji"
      syndrome); clinical severity; delayed hypersensitivity; and sticky-tape sampling
      and microscopic identification of nematocysts. RESULTS: Patients were aged 2-50
      years, with eight aged under 15 years; 23 were male. Presentations were
      consistent with C. fleckeri sting in 28 cases, Darwin carybdeid sting in five,
      and Irukandji syndrome in four. Sticky-tape sampling was done in 39 patients and
      was positive for C. fleckeri nematocysts in 23 and for non-C. fleckeri
      nematocysts in six, with nematocysts not detected in 10 (including all four with
      Irukandji syndrome). All microscopically confirmed C. fleckeri stings had typical
      clinical presentations. None of the stings were life-threatening, and no
      antivenom was given. Delayed hypersensitivity reactions were seen in 11 of the 19
      patients (58%) followed up after stings positive for C. fleckeri nematocysts.
      CONCLUSIONS: Although most jellyfish stings presenting to Royal Darwin Hospital I
      were caused by C. fleckeri, severe envenomation was rare. There was a strong
      association between clinical features and sticky-tape identification of
      nematocysts. Delayed hypersensitivity was common after C. fleckeri stings.

PMID- 11837878
TI  - Carols in the wind.
AB  - AIM: To compare mood and emotional responses to music played on pipe organs and
      pipeless (digital) organs. DESIGN: A two-organ (pipe v. digital) crossover study.
      SETTING: St Theodore's Anglican Church, Adelaide. SUBJECTS: 43 non-musician
      volunteers. MAIN OUTCOME MEASURES: Changes in mood and emotions measured by the
      Profile of Mood States. RESULTS: Both instruments produced significant reductions
      in the emotions commonly experienced during the Christmas season: tension
      anxiety, depression-rejection, anger-hostility and fatigue. There were no
      significant changes for vigour or confusion-bewilderment, and no significant
      differences between the mood-altering effects of the two instruments.
      CONCLUSIONS: Pipeless organs are as effective as pipe organs in inducing
      beneficial mood changes.

PMID- 11837879
TI  - The personal digital assistant, a new medical instrument for the exchange of
      clinical information at the point of care.
AB  - Personal digital assistants can provide a portable, integrated platform for point
      of-care clinical reference, patient management and data communication. Clinical
      reference programs allow the user to access information from the Internet and
      guidelines. Patient management programs allow doctors to access and store
      clinical information. Wireless technologies have potential for rapid exchange of
      clinical laboratory results and efficient "electronic patient handovers". Thus,
      these devices provide the potential for true continuity of care across the
      healthcare system.

PMID- 11837880
TI  - Books as carriers of disease.

PMID- 11837882
TI  - Conference baggery.

PMID- 11837881
TI  - Bloodletting and leeching: instruments of healing or torture?

PMID- 11837883
TI  - The mystery of GP research output?

PMID- 11837884
TI  - Australian general practice at a fork in the road: which way forward?

PMID- 11837885
TI  - Medical research into "neglected diseases".

PMID- 11837886
TI  - Economy class syndrome: a forgotten lesson.

PMID- 11837887
TI  - Improving the treatment of leg ulcers.

PMID- 11837888
TI  - Taenia solium and neurocysticercosis.

PMID- 11837889
TI  - Eye exposure to squashed spiders.

PMID- 11837890
TI  - Kangaroo capers.

PMID- 11837891
TI  - GABA and GABA receptors in the central nervous system and other organs.
AB  - Gamma-aminobutyrate (GABA) is a major inhibitory neurotransmitter in the adult
      mammalian brain. GABA is also considered to be a multifunctional molecule that
      has different situational functions in the central nervous system, the peripheral
      nervous system, and in some nonneuronal tissues. GABA is synthesized primarily
      from glutamate by glutamate decarboxylase (GAD), but alternative pathways may be
      important under certain situations. Two types of GAD appear to have significant
      physiological roles. GABA functions appear to be triggered by binding of GABA to
      its ionotropic receptors, GABA(A) and GABA(C), which are ligand-gated chloride
      channels, and its metabotropic receptor, GABA(B). The physiological,
      pharmacological, and molecular characteristics of GABA(A) receptors are well
      documented, and diversity in the pharmacologic properties of the receptor
      subtypes is important clinically. In addition to its role in neural development,
      GABA appears to be involved in a wide variety of physiological functions in
      tissues and organs outside the brain.

PMID- 11837892
TI  - Cell type specific expression of secretory TFF peptides: colocalization with
      mucins and synthesis in the brain.
AB  - The "TFF domain" is an ancient cysteine-rich shuffled module forming the basic
      unit for the family of secretory TFF peptides (formerly P-domain peptides and
      trefoil factors). It is also an integral component of mosaic proteins associated
      with mucous surfaces. Three mammalian TFF peptides are known (i.e., TFF1-TFF3);
      however, in Xenopus laevis the pattern is more complex (xP1, xP4.1, xP4.2, and
      xP2). TFF peptides are typical secretory products of a variety of mucin-producing
      epithelial cells (e.g., the conjunctiva, the salivary glands, the
      gastrointestinal tract, the respiratory tract, and the uterus). Each TFF peptide
      shows an unique expression pattern and different mucin-producing cells are
      characterized by their specific TFF peptide/secretory mucin combinations. TFF
      peptides have a pivotal role in maintaining the surface integrity of mucous
      epithelia in vivo. They are typical constituents of mucus gels, they modulate
      rapid mucosal repair ("restitution") by their motogenic and their cell scattering
      activity, they have antiapoptotic effects, and they probably modulate
      inflammatory processes. Pathological expression of TFF peptides occurs as a
      result of chronic inflammatory diseases or certain tumors. TFF peptides are also
      found in the central nervous system, at least in mammals. In particular, TFF3 is
      synthesized from oxytocinergic neurons of the hypothalamus and is released from
      the posterior pituitary into the bloodstream.

PMID- 11837893
TI  - Molecular patterning along the sea urchin animal-vegetal axis.
AB  - The molecular regulatory mechanisms underlying primary axis formation during sea
      urchin development have recently been identified. Two opposing maternally
      inherited systems, one animalizing and one vegetalizing, set up the animal
      vegetal (A-V) axis. The vegetal system relies in part on the Wnt-beta-catenin
      Tcf/Lef signaling pathway and the animal system is based on a cohort of
      animalizing transcription factors that includes members of the Ets and Sox
      classes. The two systems autonomously define three zones of cell-type
      specification along the A-V axis. The vegetalmost zone gives rise to the
      skeletogenic mesenchyme lineage; the animalmost zone gives rise to ectoderm; and
      the zone in which the two systems overlap generates endoderm, secondary
      mesenchyme, and ectoderm. Patterning along the A-V also depends on cellular
      interactions involving Wnt, Notch, and BMP signaling. We discuss how these
      systems impact the formation of the second axis, the oral-aboral axis; how they
      connect to later developmental events; and how they lead to cell-type-specific
      gene expression via cis-regulatory networks associated with transcriptional
      control regions. We also discuss how these systems may confer on the embryo its
      spectacular regulatory capacity to replace missing parts.

PMID- 11837894
TI  - Cell and molecular cell biology of melanin-concentrating hormone.
AB  - Recent advances in the study of melanin-concentrating hormone (MCH) have depended
      largely on molecular biological techniques. In mammals, which have attracted the
      most attention, novel findings concern (i) the MCH gene, which can yield several
      peptides by either posttranslational cleavage or alternative splicing, as well as
      bidirectional transcription; (ii) the identification of two G protein-coupled MCH
      receptors in the brain and peripheral tissues; and (iii) the evidence for
      subpopulations of MCH neurons in the central nervous system, characterized by
      their chemical phenotypes, connections, and individual physiological responses to
      different physiological paradigms. The involvement of central MCH in various
      functions, including feeding, reproduction, stress, and behavior patterns, is
      reviewed. The stage during evolution at which MCH may have acquired
      hypophysiotrophic and hormonal functions in lower vertebrates is considered in
      light of morphological data. Evidence that MCH also has peripheral
      paracrine/autocrine effects in mammals is provided.

PMID- 11837895
TI  - Neuroendocrine control of pheromone biosynthesis in moths.
AB  - Prevalent among the Lepidoptera, as in many other insect orders, species-specific
      pheromones are synchronously produced and released for mate finding. Pheromone
      biosynthesis activating neuropeptide (PBAN) is a neuropeptide widespread
      throughout the class Insecta. Although its role in the several different orders
      of insects has not been fully elucidated, its regulatory role in Lepidopteran
      pheromone biosynthesis has been strongly implicated. The biosynthesis, gene
      expression, distribution, and release of PBAN have been studied in several moth
      species. This review discusses PBAN's mode of action as a pheromonotropic
      neurohormone at the organism, tissue, and cellular levels. The discussion
      includes an overview on PBAN structure-activity relationships, its target tissue
      identification, its putative receptor proteins, and the second messengers
      involved in signal transduction and the key regulatory enzymes in the pheromone
      biosynthetic pathway that may be influenced by PBAN. Finally, the review includes
      a discussion of various mediators and inhibitors of the pheromonotropic action
      due to PBAN.

PMID- 11837896
TI  - Gene transfer to salivary glands.
AB  - This article provides a review of the application of gene transfer technology to
      studies of salivary glands. Salivary glands provide an uncommon target site for
      gene transfer but offer many experimental situations likely of interest to the
      cell biologist. The reader is provided with a concise overview of salivary
      biology, along with a general discussion of the strategies available for gene
      transfer to any tissue. In particular, adenoviral vectors have been useful for
      proof of concept studies with salivary glands. Several examples are given, using
      adenoviral-mediated gene transfer, for addressing both biological and clinical
      questions. Additionally, benefits and shortcomings affecting the utility of this
      technology are discussed.

PMID- 11837897
TI  - German vets trained in homeopathy.

PMID- 11837898
TI  - AVA's stance on tail docking of dogs.

PMID- 11837899
TI  - UK and American "dangerous dogs" legislation.

PMID- 11837900
TI  - The rural vets crisis.

PMID- 11837901
TI  - Therapy for Australian cats with lymphosarcoma.
AB  - OBJECTIVE: To determine the response of Australian cats with lymphosarcoma to
      chemotherapy and/or surgery in relation to patient and tumour characteristics,
      haematological and serum biochemical values and retroviral status. DESIGN:
      Prospective study of 61 client-owned cats with naturally-occurring lymphosarcoma
      subjected to multi-agent chemotherapy and/or surgery. PROCEDURE: An accepted
      chemotherapy protocol utilising l-asparaginase, vincristine, cyclophosphamide,
      doxorubicin, methotrexate and prednisolone was modified and used to treat 60 cats
      with lymphosarcoma. Clinical findings were recorded before and during therapy. As
      far as practical, cases were followed to death, euthanasia or apparent cure.
      Owner satisfaction with the results of chemotherapy was determined using a
      questionnaire sent after the completion of chemotherapy. RESULTS: One cat, with
      lymphosarcoma limited to a single mandibular lymph node, was treated using
      surgery alone and was cured. The other 60 cats were treated using multi-agent
      chemotherapy, although seven cats with localised intestinal, ocular and
      subcutaneous lesions had these lesions partially (2 intestinal lesions) or
      completely (2 eyes, 2 intestinal lesions and a cluster of regional lymph nodes)
      resected prior to starting chemotherapy. The median survival time for these 60
      cats was 116 days. Of the 60 cats, 48 rapidly went into complete remission
      following the administration of 1-asparaginase, vincristine and prednisolone
      (complete remission rate 80%) and these cats had a median survival of 187 days.
      Three cats were censored from further analysis as their long-term survival data
      were uninterpretable because they died of causes unrelated to lymphosarcoma or
      were prematurely lost to follow-up. Twenty cats were classed as 'long-term
      survivors' based on survival time in excess of one year and at least 14 were
      'cured' based on the absence of physical evidence of lymphosarcoma 2-years after
      initiating treatment. In other words, of the 48 cats that reached complete
      remission, in excess of 29% were 'cured'. Despite detailed analysis, few
      meaningful prognostic indicators based on patient or tumour characteristics were
      identified, although long-term survivors were more likely to be less than 4-years
      (P= 0.04) and to have tumours of the T-cell phenotype (P= 0.06). Excluding the
      one FeLV ELISA-positive cat with mediastinal LSA, 7 of 9 cats less than 4 years
      of-age were long-term survivors (median survival time >1271 days). There was a
      strong association between achieving complete remission and long-term survival (P
      = 0.003). On the basis of 27 replies to a questionnaire, owners were generally
      very satisfied with the response to chemotherapy, irrespective of the survival
      time of the individual patient. Eighty five percent of owners expressed complete
      satisfaction with their decision to pursue chemotherapy and 70% believed their
      cat's health status improved during the first 2-weeks of treatment. Importantly,
      78% of owners considered that chemotherapy required a very substantial time
      commitment on their part. CONCLUSIONS: It was possible to cure approximately one
      quarter of cats with lymphosarcoma using sequential multi-agent chemotherapy
      and/or surgery. FeLV-negative cats younger than 4 years (typically with
      mediastinal lymphosarcoma) had a particularly favourable prognosis. The decision
      to embark on chemotherapy should be based on the results of induction
      chemotherapy with l-asparaginase, vincristine and prednisolone, as the response
      to this was a good predictor of long-term survival. Cats surviving the first 16
      weeks of chemotherapy generally enjoyed robust remissions (in excess of 1 year)
      or were cured of their malignancy.

PMID- 11837902
TI  - Laryngeal rhabdomyoma in a dog.
AB  - A 4-year-old spayed female Golden Retriever was presented for investigation of
      progressive loss of bark, continuous panting and increased upper respiratory
      noise. Examination of the larynx and pharynx under general anaesthesia identified
      a spherical 5 x 3 cm mass involving the right arytenoid cartilage. Cytological
      examination of fine needle aspirates from the mass suggested the tumour was a
      carcinoma, however histological examination in association with immunoperoxidase
      and histochemical staining identified the mass as a laryngeal rhabdomyoma.

PMID- 11837903
TI  - Surgical correction of carpal valgus deformity in three alpacas.
AB  - Two alpaca crias and one 14-month-old alpaca were referred for treatment of
      bilateral carpal valgus. In one cria, hemi-circumferential periosteal transection
      and elevation combined with an ulna osteotomy was performed initially without
      success, however transphyseal bridging with screws and wires was used
      successfully in both crias to straighten the limbs. As the distal radial and ulna
      growth plates had closed in the 14-month-old alpaca, bilateral wedge ostectomies
      of the distal radius and transfixation casts were used to straighten and
      stabilise the limbs. The ostectomy sites healed and the alpaca is ambulatory,
      although carpal flexion is significantly reduced. Until the relationship between
      the growth rate of crias and the success of hemicircumferential periosteal
      transection and elevation and ulna osteotomy is established, transphyseal
      bridging may provide a more reliable result in crias with carpal valgus deformity
      and open physes. Wedge ostectomy and application of a transfixation cast can be
      used to correct severe carpal valgus deformities in alpacas with closed physes.

PMID- 11837904
TI  - An estimate of the economic effects of cattle tick (Boophilus microplus)
      infestation on Queensland dairy farms.
AB  - OBJECTIVE: To establish the cost to the Queensland dairy industry of cattle tick
      infestation and its control, excluding the costs incurred from control measures
      directed specifically at tick fever and morbidity and mortality arising from tick
      fever. STUDY DESIGN: Economic models are described that have been based on
      empirical data relating to liveweight and milk yield loss, and on a survey of
      control practices and tick infestation. The first two models were designed to
      estimate costs of control and losses resulting from tick infestation on a single
      dairy farm. The third model developed estimates of the cost of tick infestation
      for each of four regions within the tick-infested area of Queensland. RESULTS:
      The overall cost to the Queensland dairy industry of the cattle tick (excluding
      the costs associated specifically with tick fever) and based on 1998 management
      practices, was $4,096,000 per annum. About 49% of this cost was related to the
      costs of control and 51% to losses in production. CONCLUSION: Cattle tick
      infestation represents a significant impost on dairy producers in Queensland, and
      although the actual cost will change as deregulation results in economic changes
      in the industry, infestations of ticks will continue to be expensive to control.

PMID- 11837905
TI  - Immunity following use of Australian tick fever vaccine: a review of the
      evidence.
AB  - OBJECTIVE: To review the evidence available on the degree and duration of
      immunity provided by Australian tick fever vaccines against Babesia bovis, B.
      bigemina and Anaplasma marginale infections in Australia and overseas.
      BACKGROUND: Vaccines containing attenuated strains of B bovis and B bigemina as
      well as A. centrale grown in splenectomised calves have been used in Australia
      since 1964 to immunise cattle against tick fever. About 800,000 doses of vaccine
      are supplied annually and much of the evidence for protection is field evidence
      rather than conventional immunological measures or pen trials. CONCLUSIONS:
      Immunity to Babesia bovis and B. bigemina--A single inoculation generally
      provides sound, long-lasting protection both in Australia and overseas. No
      evidence was found of a loss of immunity with time. Vaccine failures to B. bovis
      do occur, but are uncommon and evidently caused by a number of factors, including
      immune responsiveness of the vaccinated animals, and immunogenicity of the
      vaccine strain. Immunity to Anaplasma marginale--The vaccine containing A.
      centrale provides partial, variable protection against A. marginale. Protection
      against challenge in Australia is adequate in most cases to prevent disease and
      use of the vaccine in this country appears to be justified. Protection against
      antigenically diverse, highly virulent stocks of A. marginale in other countries
      is, at times, clearly inadequate and better vaccines are required in situations
      where the challenge is severe.

PMID- 11837906
TI  - Reduced efficacy of ivermectin, abamectin and moxidectin against field isolates
      of Haemonchus contortus.
AB  - OBJECTIVES: To investigate the reduced efficacy of ivermectin, abamectin and
      moxidectin against two field isolates of Haemonchus contortus. These isolates
      were identified on separate properties in the New England region of New South
      Wales. PROCEDURE: Reduced efficacy of macrocyclic lactone anthelmintics against
      two field isolates of H contortus was suspected. These isolates were obtained
      from sheep on separate farms and pen trials were performed to investigate the
      efficacy of macrocyclic lactones. The percentage efficacy was calculated for
      moxidectin, ivermectin and closantel against the isolate from one farm (VHR23)
      and for moxidectin, ivermectin and abamectin against the isolate from the second
      (VHR29). The persistent activity of moxidectin against both isolates was
      investigated. RESULTS: Ivermectin and closantel were found to have efficacies
      below 80% against established populations of VHR23. Moxidectin was effective
      against an established population of VHR23 but the persistent activity was
      reduced to 7 days. Moxidectin was also found to be effective against established
      populations of VHR29, however, ivermectin and abamectin were found to have
      efficacies below 80%. There was no evidence of persistent activity of moxidectin
      against VHR29. CONCLUSION: A reduction in efficacy of abamectin and/or ivermectin
      against field isolates of H. contortus was identified from two farms in the New
      England region of New South Wales. The persistent effect of moxidectin was
      reduced against both isolates.

PMID- 11837907
TI  - Paraquat poisoning in sheep from contaminated water.

PMID- 11837908
TI  - Profiles of currents during electrical stunning.

PMID- 11837909
TI  - Pertussis--United States, 1997-2000.
AB  - Pertussis was a major cause of morbidity and mortality among infants and children
      in the United States during the prevaccine era (i.e., before the mid-1940s).
      Following the introduction and widespread use of whole-cell pertussis vaccine
      combined with diphtheria and tetanus toxoids (DTP) among infants and children in
      the late 1940s, the incidence of reported pertussis declined to a historic low of
      1,010 cases in 1976 (Figure 1). However, since the early 1980s, reported
      pertussis incidence has increased cyclically with peaks occurring every 3-4
      years. In 1996, less reactogenic acellular pertussis vaccines (DTaP) were
      licensed and recommended for routine use among infants. This report summarizes
      national surveillance data for pertussis during 1997-2000 and assesses the
      effectiveness of pertussis vaccination in the United States during this period.
      The findings indicate that pertussis incidence continues to increase in infants
      too young to receive 3 doses of pertussis-containing vaccine and in adolescents
      and adults. Prevention efforts should be directed at maintaining high vaccination
      rates and managing pertussis cases and outbreaks.

PMID- 11837910
TI  - Hypothermia-related deaths--Utah, 2000, and United States, 1979-1-998.
AB  - Hypothermia is a medical emergency that is completely preventable. Hypothermia
      occurs when persons are exposed to ambient cold temperatures without appropriate
      protection for extended periods of time. The clinical definition of hypothermia
      is a core body temperature < or = 95 F (35 C). This report describes cases of
      hypothermia-related deaths in Utah during 2000 and describes unintentional
      hypothermia-related deaths in the United States during 1979-1998. The Utah cases
      illustrate risk factors and environmental conditions associated with hypothermia.

PMID- 11837911
TI  - Update: Influenza activity--United States, 2001-02 season.
AB  - Although influenza activity in the United States remained low from October
      through mid-January, the number and percentage of specimens testing positive for
      influenza viruses have increased in recent weeks. Laboratory-confirmed influenza
      infections have been reported from 45 states. The predominant influenza viruses
      isolated this season have been type A (H3N2) viruses that are well matched by
      this season's influenza vaccine. This report summarizes U.S. influenza activity
      from September 30, 2001 through January 19, 2002 and updates the previous
      summary.

PMID- 11837912
TI  - Musculoskeletal images. C3 aneurysmal bone cyst.

PMID- 11837913
TI  - Musculoskeletal case 20. Jefferson fracture (C1 burst fracture).

PMID- 11837914
TI  - Soft-tissue case 43. Cecal volvulus: differentiating distended viscus from
      pneumoperitoneum.

PMID- 11837915
TI  - Chung RS, Rowland DY. Meta-analyses of randomized controlled trials of
      laparoscopic vs conventional inguinal hernia repairs. Surg Endosc 1999;13(7):689
      94.

PMID- 11837916
TI  - Thoracolumbar spine fractures: is there a problem?
AB  - Every physician who treats injured patients has a responsibility to detect and
      appropriately manage thoracolumbar spinal column injuries. Fractures of the
      thoracolumbar spine are relatively common, so clinicians must give them every
      consideration both to protect from secondary spinal cord injury and to appreciate
      the extent of the patient's injuries. Other extraspinal as well as noncontiguous
      injuries to the spinal column are frequently present. Unfortunately,
      thoracolumbar spine fractures are often missed or diagnosed late in clinical
      series. In an era of cost-containment, not all responsive patients require full
      thoracolumbar spine radiographs. In awake, alert, nonintoxicated patients with
      simple injury mechanisms, these fractures can be ruled out through physical
      examination, if the patient has no physical findings and does not have other
      serious injuries. However, concern has recently been raised that some patients
      may have "asymptomatic" fractures that may be missed without radiography. The
      evidence reveals that fractures are not truly asymptomatic but may be masked by
      other distracting injuries, making them fractures occult rather than
      asymptomatic. Clinicians and subsequently their patients will always be at risk
      if this important distinction is forgotten.

PMID- 11837917
TI  - Surgical treatment of thymoma.
AB  - OBJECTIVE: To describe experience with the surgical treatment of thymoma. DESIGN:
      A retrospective study. SETTING: A teaching hospital at the University of Ottawa.
      PATIENTS: Over 25 years, 42 consecutive patients (22 men, 20 women) who had a
      thymoma requiring operation. INTERVENTIONS: Thymectomy. OUTCOME MEASURES: Age,
      sex, association with myasthenia gravis, presence of a paraneoplastic syndrome,
      extent of surgical resection, tumour size, histologic features of the tumour,
      clinical staging of the thymoma and short- and long-term outcome after surgery.
      RESULTS: The mean (and standard deviation) age of the patients was 52.8 (12.5)
      years. Thirteen patients had myasthenia gravis. With respect to tumour staging,
      24 patients had stage I, 7 had stage II and 11 had stage III disease. Three
      patients were lost to follow-up. Radiotherapy was used as an adjunct to surgical
      treatment in 83% of patients with stages II and III disease. Fifty-one percent of
      patients available for follow-up survived 175.1 months, and the cumulative 5- and
      10-year overall survival rates were 87.3% and 81.4% respectively. Only 1 patient
      died of metastatic thymoma. Complete or partial remission of myasthenia gravis
      was seen in 10 (77%) affected patients. Mixed cellular histologic features and a
      tumour size of less than 115 cm3 were more commonly seen with stage I disease.
      CONCLUSIONS: Thymomas are characterized by slow growth and prolonged survival
      even in patients with invasive disease as long as the tumour is resected
      completely and treatment is accompanied by radiotherapy.

PMID- 11837918
TI  - How long do patients wait for elective general surgery?
AB  - OBJECTIVE: Because data published on waiting times are largely determined from
      questionnaire-type surveys, which generate inconclusive opinion-based results,
      the objective of this study was to provide a quantitative measure of the extent
      and variance of waiting times among 3 elective general surgery procedures DESIGN:
      A prospective case study. SETTING: The Royal Alexandra Hospital, Edmonton.
      PATIENTS: From Feb. 1 to Mar. 15, 1999, all cases (90 patients) for each
      designated procedure--open or laparoscopic cholecystectomv for biliary colic or
      cholelithiasis, segmental resection or modified radical mastectomy for breast
      carcinoma and colon or rectal resection for colorectal carcinoma--were tabulated
      daily from the hospital elective operating lists. Data were prospectively
      acquired from individual surgeon offices (11 surgeons). Sixteen of the 90
      patients were excluded, leaving 74 for analysis. OUTCOME MEASURES: Time in days
      from initial referral by the general practitioner to the surgeon (T1), time in
      days from the initial visit with the surgeon to operation for patients requiring
      no further diagnostic work-up by the surgeon (T2A), and time in days from the
      initial visit with the surgeon to operation for patients requiring further
      diagnostic work-up (T2B). RESULTS: The waiting period for patients who underwent
      non-cancer-related procedures (cholecystectomy) ranged from 83 to 106 days;
      patients with breast cancer waited an average of 24 (T1 + T2A) to 66 (T1 + T2B)
      days from the day of referral to the date of surgery and those with colorectal
      cancer waited an average of 32 (T1 + T2A) to 51 (T1 + T2B) days from the time of
      referral to operation (p < 0.05). CONCLUSION: This preliminary report aimed at
      quantitative measurement of time spent waiting for elective general surgery
      indicates that patients who underwent non-cancer-related procedures waited
      significantly longer for their surgery than patients who required procedures for
      cancer.

PMID- 11837919
TI  - Health service costs for patients on the waiting list.
AB  - OBJECTIVE: To find out if the cost of health services was artificially increased
      because of a delay in surgery due to a lack of resources. DESIGN: A retrospective
      cohort study. SETTING: Three urban hospitals in Calgary, Alta. PATIENTS: The
      study cohort comprised 4441 patients (1 index procedure for each patient).
      INTERVENTIONS: Cholecystectomy, discectomy, hysterectomy, total knee and total
      hip replacements. OUTCOME MEASURES: The costs for physician claims, use of home
      care and pharmaceutical prescriptions 1 year before and after the selected
      procedures, using 1997/98 administrative records and waiting times maintained by
      Alberta Health and Wellness and Calgary Regional Health Authority. RESULTS: The
      median wait for joint surgery (88 d for knee replacements and 65 d for hip
      replacements) was longer than for the other selected procedures (29 d for
      cholecystectomies, 21 d for discectomies and 42 d for hysterectomies). Total per
      patient physician claim costs decreased after surgery (cholecystectomy--30%,
      discectomy--24%, hip replacement--6%, hysterectomy--23% and knee replacement-
      4%). Seeing the procedure specialist more than once preoperatively was associated
      with a greater decrease in postoperative physician claim costs. Longer waits were
      not associated with more physician claim costs or Blue Cross prescriptions claim
      costs for seniors (> or = 65 yr) in the year before or after surgery nor were
      they associated with more physician claim costs during the actual wait compared
      with a matched postoperative time period. CONCLUSIONS: No evidence was found to
      suggest that waiting for 1 of 5 common surgical procedures is correlated with
      greater health service expenditures pre- or postoperatively. In this study, wait
      time is not a proxy for health service use nor do health service costs decrease
      markedly after surgery.

PMID- 11837920
TI  - Isolated rib fractures in elderly patients: mortality and morbidity.
AB  - OBJECTIVES: To describe the management, morbidity and mortality seen with
      isolated rib fractures in elderly patients and assess the need for
      hospitalization. DESIGN: A case series. SETTING: A tertiary care centre in Tel
      Aviv. METHODS: Hospital records of 77 elderly patients (age 65 yr and older)
      admitted with isolated rib fractures were reviewed over a 9-year period. MAIN
      OUTCOME MEASURES: Demographic, medical and hospitalization data, blood hemoglobin
      and oxygen saturation levels. RESULTS: The number of fractured ribs was found to
      correlate with the morbidity (p = 0.027) and mortality (p = 0.006). There were no
      significant differences in these rates with respect to comorbidity except for
      diabetes (higher morbidity) and congestive heart failure (higher mortality).
      Twenty-eight patients (36%) had pulmonary complications and 1 had cardiac
      complications. Pulmonary complications were fatal in 6 patients (7.8%).
      Multivariate analysis of the factors related to morbidity demonstrated that only
      oxygen saturation (p = 0.0009) and diabetes (p = 0.03) correlated significantly.
      CONCLUSIONS: In spite of significant morbidity and mortality in elderly patients
      with isolated rib fractures, prediction of the prognosis for these patients is
      presently not possible. Admission for observation and treatment is therefore
      justified and beneficial.

PMID- 11837921
TI  - Computerized management of oral anticoagulant therapy: experience in major joint
      arthroplasty.
AB  - OBJECTIVE: Evaluation of the safety and potential cost savings of a computerized,
      laboratory-based program to manage inpatient warfarin thromboprophylaxis after
      major joint arthroplasty. DESIGN: A consecutive-case study of adults. SETTING: A
      tertiary care orthopedic institution. PATIENTS: Patients requiring joint
      arthroplasty who had no recent episodes of thromboembolic disease, no mechanical
      heart valve, atrial fibrillation, severe liver disease or baseline international
      normalized ratio [INR] greater than 1.3 admitted over a 54-month period (July
      1994-December 1998). All patients received a standard regimen of warfarin
      beginning on the evening after the operation. Four hundred and thirty randomly
      selected patients managed by the program were followed up by telephone survey 3
      months after discharge. Patients exhibiting erratic responses to warfarin were
      withdrawn from the program and managed individually thereafter. INTERVENTION:
      Major joint arthroplasty with warfarin therapy administered through the
      computerized program. MAIN OUTCOME MEASURES: Test results maintained within the
      desired therapeutic range (INR 2.0-3.0), clinically severe bleeding episodes,
      readmission rates, clinically symptomatic and venographically proven episodes of
      venous thrombosis or pulmonary embolism. RESULTS: Over the study period 5629
      patients underwent joint arthroplasty; 5,372 patients were considered for the
      program; 332 patients were ineligible and were managed individually; 311 entered
      patients did not complete the program. This left 4,729 patients who completed the
      program. In 2932 (62%) patients test results were maintained in the desired
      therapeutic range. The major bleeding rate was less than 0.5%, the readmission
      rate was 3.8%, the deep venous thrombosis rate was 3.7% and the pulmonary
      embolism rate was 0.2% with no thromboembolic related deaths in the small sample
      cohort. CONCLUSIONS: The majority of patients requiring warfarin
      thromboprophylaxis can be safely and effectively managed by this laboratory-based
      computerized program while in hospital. Significant potential cost savings in
      nursing time could be achieved.

PMID- 11837922
TI  - Refracture rate after plate removal from the radial metaphysis.
AB  - OBJECTIVES: To document the refracture rate after removal of internal fixation at
      the metaphyseal region of the distal radius and to compare this rate to that
      associated with diaphyseal plate removal reported in the literature. DESIGN: A
      chart review with telephone follow-up. SETTING: Three tertiary care hospitals (in
      Ottawa, Burlington, Vt., and London, Ont.). PATIENTS: Fifty-three patients (54
      radii) underwent elective removal of internal fixation of the distal radius after
      distal metaphyseal procedures. The mean follow-up was 46.8 months. MAIN OUTCOME
      MEASURE: The refracture rate. RESULTS: No refractures were reported after plate
      removal, and the overall complication rate was minimal. CONCLUSIONS: The
      refracture rate at the metaphvsis of the radius after plate removal is lower than
      the rate after diaphyseal plate removal reported in the literature.

PMID- 11837923
TI  - Surgical case costing: trauma is underfunded according to resource intensity
      weights.
AB  - OBJECTIVE: To determine whether rate-based funding using resource intensity
      weights (RIWs) adequately represents trauma case costs. DESIGN: A prospective
      time-in-motion resource utilization pilot study to assure the effectiveness of
      the computerized hospital Transition-One data acquisition system, followed by a
      retrospective observational case costing study. Patient costs with no identifing
      data were used, and all costs were tabulated as mean cost per group. SETTING:
      London Health Sciences Centre, London, Ont., a tertiary care "lead" trauma
      hospital. PATIENTS: A modified random selection of 4 control case mix groups
      (CMGs) of surgical patients for the fiscal year 1996-97. The trauma group was
      selected as a representative resource-intensive CMG. Each patient was assigned to
      a CMG by Health Records according to the most responsible diagnosis. OUTCOMES
      MEASURES: Total case costs were tabulated for each patient then combined for a
      mean case cost per CMG. The RIW assignments for each patient were combined to
      create a mean RIW per CMG and mean length of stay per CMG. RESULTS: There was no
      statistically significant difference between the control surgical CMGs and the
      trauma CMG for mean RIW-adjusted length of stay per CMG, but there was a
      significant difference (p < 0.0001) between the control CMGs and the trauma CMG
      for RIW-adjusted mean case cost per CMG. CONCLUSIONS: RIWs underrepresent trauma
      case costs by a factor of 3.5, which could result in underfinding and potential
      fiscal difficulties for leading trauma hospitals as has occurred in the United
      States.

PMID- 11837924
TI  - Popliteal artery false aneurysm secondary to tibial osteochondroma.

PMID- 11837925
TI  - Allocation of health resources.

PMID- 11837926
TI  - Percutaneous drainage for liver hydatid cysts.

PMID- 11837927
TI  - Ecthyma gangrenosum.

PMID- 11837928
TI  - Surgical residency programs.

PMID- 11837929
TI  - The pendulum.

PMID- 11837930
TI  - Allocation of scarce resources: assessment and impact.

PMID- 11837931
TI  - Soft-tissue images. Trocar-site hernia after laparoscopic procedures.

PMID- 11837932
TI  - Suppressive effects of cyclosporine A on neutrophils and T cells may be related
      to therapeutic benefits in patients with steroid-resistant ulcerative colitis.
AB  - An intravenous infusion of cyclosporine A (CsA) shows clinical benefits in
      patients with steroid-resistant ulcerative colitis (UC). To clarify its
      mechanisms, we investigated the ability of CsA to inhibit the functions of
      neutrophils and T cells. The cytotoxic activity by mucosal T cells was analyzed
      by anti-CD3-triggered cytotoxicity after lamina propria mononuclear cells were
      cultured with recombinant interleukin (IL)-2. The chemotactic response, the
      generation of superoxide, and the production of chemokines, IL-8, and macrophage
      inflammatory protein-1alpha by neutrophils were examined using a multiple-well
      chamber assay, a chemiluminescence method, and an enzyme-linked immunosorbent
      assay (ELISA), respectively. Mucosal chemokine activity was determined by an
      ELISA using the organ culture supernatant of mucosal biopsy tissues. Pretreatment
      with CsA caused consistent inhibitions of cytotoxic activity by mucosal T cells
      and chemotactic migration, superoxide generation, and chemokine production by
      neutrophils mostly in a dose-dependent manner. In patients who received an
      intravenous infusion of CsA, mucosal chemokine activity decreased after therapy
      in parallel with decreases in the numbers of neutrophils and mononuclear cells in
      the biopsy tissues. These results suggest that suppressive effects of CsA on
      neutrophils and T cells may be related to therapeutic benefits in patients with
      steroid-resistant UC.

PMID- 11837933
TI  - Preliminary study of ciprofloxacin in active Crohn's disease.
AB  - Based on limited reports of the successful use of antibiotics in the treatment of
      Crohn's disease (CD) and on the possibility that intestinal bacteria may be one
      of the etiologic factors playing a role in the pathogenesis of this condition, we
      undertook a study to evaluate the use of a broad-spectrum antibiotic in CD. Our
      team studied the efficacy of adding the antibiotic ciprofloxacin to the treatment
      of moderately active, but resistant cases of CD. Forty-seven adults with
      moderately active CD were randomly assigned treatment with ciprofloxacin 500 mg
      twice daily versus placebo twice daily for 6 months. The primary endpoint was the
      change in scores on the Crohn's Disease Activity Index (CDAI) from baseline to
      month 6. Although 47 patients were randomized, at 1 month of follow-up 28
      patients received ciprofloxacin and 19 received placebo. The mean entry CDAI
      scores were not significantly different: 187 for the ciprofloxacin group versus
      230 for the placebo group (p = 0.638). Mean CDAI scores at the completion of
      study were 112 for the ciprofloxacin group (n = 25) and 205 for the placebo group
      (n = 12), (p < 0.001). Disease remission is defined as a decrease in the CDAI
      score to less than 150 points. Our preliminary study suggests that ciprofloxacin
      may be an effective agent when added to the treatment of moderately active,
      resistant CD.

PMID- 11837934
TI  - Value of rectosigmoidoscopy with biopsies for diagnosis of inflammatory bowel
      disease in children.
AB  - BACKGROUND: In children with inflammatory bowel disease (IBD), treatment depends
      on the type and extent of disease. Therefore, maximal effort should be made to
      provide a correct diagnosis. The aim of this study was to assess the value of a
      histologic diagnosis made on the basis of either ileal and colonic or
      rectosigmoid biopsies. METHODS: In 42 children with a known diagnosis of IBD,
      biopsies from rectum and sigmoid were reassessed by an expert, blinded
      pathologist. This histologic diagnosis was compared with the diagnosis based on
      (ileo)colonic biopsies and the final diagnosis. RESULTS: In patients with IBD,
      diagnostic accuracy of rectosigmoid histology was 0.4524. For (ileo)colonic
      biopsies, diagnostic accuracy was 0.7619. CONCLUSIONS: Histology on biopsies from
      rectum and sigmoid is insufficient for a correct diagnosis of Crohn's disease or
      ulcerative colitis in children. At initial presentation, an ileocolonoscopy with
      biopsies should therefore be performed in all children.

PMID- 11837936
TI  - Interleukin-2-deficient mice develop colitis in the absence of CD28
      costimulation.
AB  - The intestinal lamina propria contains lymphocytes that are chronically activated
      by exposure to luminal antigens. Dysregulation of these cells is thought to be
      central to the pathogenesis of bowel inflammation in experimental models of
      inflammatory bowel disease. CD28 signals on peripheral T cells provide important
      costimulatory signals that enhance T-cell proliferation and activation responses
      to antigens. However, the role of CD28 signals in lamina propria T cells or
      models of inflammatory bowel disease have not been determined. Accordingly, we
      examined T lymphocyte activation and proliferation in CD28-deficient (CD28-/-)
      mice to examine the in vivo roles of CD28 signals in lamina propria T-cell
      homeostasis. We further generated CD28-/- interleukin (IL)-2-/- double mutant
      mice to assess the role of CD28 signals in supporting the spontaneously activated
      and pathogenic T cells that accumulate in IL-2-/- mice. CD28-/- lamina propria T
      cells displayed reduced activation markers, but were present in normal numbers
      and proliferated normally. IL-2-/- lymphocytes expressed high levels of bcl-xL,
      whereas CD28-/- IL-2-/- cells had substantially less bcl-xL. However,
      lymphadenopathy and ulcerative colitis-like disease occurred in both IL-2-/- and
      CD28-/- IL-2-/- mice. Thus, CD28 provides a functional costimulatory signal to
      lamina propria T cells but is not required for homeostasis of these cells. In
      addition, neither CD28 nor bcl-xL appears to be required for the spontaneous
      accumulation of T cells in IL-2-/- mice. This suggests that other costimulatory
      molecules or T-cell receptor ligation alone drive lymphocyte expansion in IL-2
      deficient mice.

PMID- 11837935
TI  - Pouchitis in a rat model of ileal J pouch-anal anastomosis.
AB  - Endorectal ileal pouch-anal anastomosis (IPAA) has become the operation of choice
      for patients with chronic ulcerative colitis. Although this procedure improves
      the quality of life, pouchitis remains a significant postoperative complication.
      Because our understanding of the pathophysiology of pouchitis may, in part, be
      due to the lack of small animal model, our aim was to develop a model of IPAA in
      a rat that mimics its clinical counterpart. Colectomy, proctectomy, construction
      of an ileal J pouch, and ileal pouch-rectal anastomosis as a model of IPAA was
      performed in Sprague-Dawley and Lewis rats. Radiographic contrast studies were
      performed to quantitate intestinal transit. The presence of activated neutrophils
      was quantified by measuring mucosal myeloperoxidase (MPO) activity. Oxidative
      stress was quantitated by measuring urinary 8-isoprostane (8-IP) levels.
      Anaerobic and aerobic bacterial counts were determined on Brucella and tryptic
      soy agar plates, respectively. Dextran sulfate sodium (DSS) was used to
      exacerbate ileal J pouch inflammation. Mortality was low, and animals gained
      weight normally after recovery. Stasis was documented radiographically. MPO
      levels were elevated (p < 0.05) in the ileal J pouch 30 and 60 days after IPAA,
      indicating an inflammation that was associated with stasis and bacterial
      overgrowth. 8-IP levels were elevated by 80% compared with controls. Oral
      administration of 5% DSS to IPAA rats with further elevated MPO and 8-IP levels
      in concert with a pouchitis-like syndrome that included the physical, gross, and
      histologic characteristics of clinical pouchitis. An understanding of the
      pathophysiology of pouchitis is essential to the future development of new
      therapeutic modalities. This model is applicable to investigating several key
      etiologic mechanisms purportedly related to pouchitis.

PMID- 11837937
TI  - Rectal cancer as a complication of stapled IPAA.
AB  - A case of rectal cancer developing several years after a stapled pelvic pouch
      procedure is described. The need for concern about leaving residual columnar
      epithelium in patients with dysplasia or a synchronous cancer is highlighted. In
      this setting, leaving long segments of native rectum is particularly ill advised.

PMID- 11837938
TI  - Laparoscopic surgery for inflammatory bowel disease: results of the past decade.
AB  - Laparoscopic colectomy is one of the most difficult laparoscopic procedures.
      Surgeons attempting to perform laparoscopic surgery for inflammatory bowel
      disease (IBD) must have significant experience with IBD and advanced laparoscopic
      skills. Surgical management for IBD may be treated with a range of laparoscopic
      procedures that vary in complexity. After 10 years of experience, studies
      comparing laparoscopy versus laparotomy are favoring laparoscopy when evaluating
      reduction in postoperative ileus, pain, and length of hospitalization,
      disability, and cosmesis. The indications and contraindications for laparoscopic
      surgery for IBD are evolving as surgical expertise and equipment improve.

PMID- 11837939
TI  - We still are more than molecules.

PMID- 11837940
TI  - Infliximab as first-line therapy for severe Crohn's disease?

PMID- 11837941
TI  - Infliximab as first-line therapy for Crohn's disease is premature.

PMID- 11837946
TI  - Ya gotta believe!

PMID- 11837944
TI  - Molecular cloning and circadian regulation of cryptochrome genes in Japanese
      quail (Coturnix coturnix japonica).
AB  - The circadian system is thought to have three components: input, pacemaker
      (internal clock), and output. Cryptochromes (Cry) are important clock genes, and
      recent findings indicate that these genes not only act as circadian
      photoreceptors but are also essential components in the negative feedback of the
      circadian system. As a first step toward understanding the avian circadian
      system, the authors tried to clone Japanese quail homologs of mammalian Crys and
      analyze their expression patterns in different circumstances. Partial cDNAs of
      qCry1 and qCry2, which are homologs of mammalian Cry1 and Cry2, respectively,
      were obtained and their gene expressions were analyzed. Both qCry1 and qCry2
      mRNAs were present in all the tissues examined. The oscillation patterns of the
      qCry1 transcripts were tissue specific and generally showed robust changes
      between daytime and nighttime; except for lung and testis tissues (which showed
      no detectable changes between daytime and nighttime), daytime levels were higher
      in all of the tissues examined. This rapid oscillation in qCry1 persisted through
      constant darkness or constant illumination, indicating that an endogenous clock
      controls these changes. In contrast, the expression of qCry2 did not oscillate in
      any tissue examined. In addition, in tissues of the pineal gland and eye,
      unexpected light exposure in the dark period was able to block the decrease in
      qCry1 transcripts or induce its expression. These findings, in conjunction with
      the established roles of CRYs in other species, led the authors to propose that
      in the circadian system, qCRYs may play important roles similar to the known
      roles of CRYs of other species, such as acting as circadian photoreceptors and as
      components of the circadian system.

PMID- 11837945
TI  - Neuropeptide Y differentially suppresses per1 and per2 mRNA induced by light in
      the suprachiasmatic nuclei of the golden hamster.
AB  - Neuropeptide Y (NPY), present in an input pathway to the suprachiasmatic nuclei
      (SCN), can block the effects of light on circadian rhythms. The authors have
      studied this interaction using an in vitro brain slice technique. Effects of NPY
      on light-induced period1 and period2 mRNA in the SCN were examined in vitro
      following a light pulse during early subjective night. Golden hamsters (n = 91)
      were housed under a 14:10 LD cycle and then moved to constant dim red light for 3
      days. Hamsters were exposed to a 5-min light pulse previously shown to induce
      phase shifts and prepared for in vitro application of NPY. Hypothalamic slices
      containing the SCN were maintained in vitro for 40 min to 4 h after the light
      pulse, then quick-frozen. Sections were evaluated by in situ hybridization with
      [35S]-labeled cRNA probes for per mRNA. Rapid light induction of both per1 and
      per2 by 40 min and 1 h after the light pulse, respectively, was apparent, with
      NPY inhibition of this response significant by at least these same time points.
      However, although striking suppression of per2 mRNA by the NPY continued through
      the peak for per2 at 2 h, per1 mRNA levels rebounded quickly to equal the per1
      induction peak at 1 h and mirrored the control light induction pattern for per1
      thereafter. Delaying NPY to 30 min after slice preparation demonstrated that NPY
      is capable of suppressing peak per1 levels. These results confirm the feasibility
      of measuring light-induced gene expression in the SCN in vitro. A differential
      regulation of per1 and per2 transcription might be of critical importance for the
      modulation of circadian responses to light.

PMID- 11837947
TI  - Getting through to circadian oscillators: why use constant routines?
AB  - Overt 24-h rhythmicity is composed of both exogenous and endogenous components,
      reflecting the product of multiple (periodic) feedback loops with a core
      pacemaker at their center. Researchers attempting to reveal the endogenous
      circadian (near 24-h) component of rhythms commonly conduct their experiments
      under constant environmental conditions. However, even under constant
      environmental conditions, rhythmic changes in behavior, such as food intake or
      the sleep-wake cycle, can contribute to observed rhythmicity in many
      physiological and endocrine variables. Assessment of characteristics of the core
      circadian pacemaker and its direct contribution to rhythmicity in different
      variables, including rhythmicity in gene expression, may be more reliable when
      such periodic behaviors are eliminated or kept constant across all circadian
      phases. This is relevant for the assessment of the status of the circadian
      pacemaker in situations in which the sleep-wake cycle or food intake regimes are
      altered because of external conditions, such as in shift work or jet lag. It is
      also relevant for situations in which differences in overt rhythmicity could be
      due to changes in either sleep oscillatory processes or circadian rhythmicity,
      such as advanced or delayed sleep phase syndromes, in aging, or in particular
      clinical conditions. Researchers studying human circadian rhythms have developed
      constant routine protocols to assess the status of the circadian pacemaker in
      constant behavioral and environmental conditions, whereas this technique is often
      thought to be unnecessary in the study of animal rhythms. In this short review,
      the authors summarize constant routine methodology and what has been learned from
      constant routines and argue that animal and human circadian rhythm researchers
      should (continue to) use constant routines as a step on the road to getting
      through to central and peripheral circadian oscillators in the intact organism.

PMID- 11837948
TI  - The suprachiasmatic nucleus exhibits diurnal variations in spontaneous excitatory
      postsynaptic activity.
AB  - A most prominent feature of neurons in the suprachiasmatic nucleus (SCN) is the
      circadian rhythm in spontaneous firing frequency. To disclose synaptic mechanisms
      associated with the rhythmic activity, the spontaneous postsynaptic activity was
      studied using whole-cell, patch clamp recordings in the ventral region of the SCN
      in slice preparations from rats. The synaptic events were compared between two
      time intervals corresponding to the highest and lowest electrical activity within
      the SCN during subjective daytime and nighttime, respectively. The gamma
      aminobutyric acid (GABA)-mediated spontaneous inhibitory activity showed no
      diurnal variations, but the excitatory activity was markedly higher in frequency,
      without differences in amplitude, during the subjective day compared to the
      subjective night. Spontaneous and evoked inhibitory synaptic events were blocked
      by the GABA(A) receptor antagonist bicuculline. The alpha-amino-hydroxy-5
      methylisoxazole-4-propionic acid (AMPA/kainate) receptor antagonist 6-cyano-7
      nitroquinoxaline-2, 3-dione (CNQX) blocked most of the excitatory activity. In
      addition, CNQX reduced the spontaneous inhibitory activity. The N-methyl-D
      aspartate antagonist D-2-amino-5-phosphonopentanoic acid reduced the inhibitory
      activity to a lesser degree, and there was no significant difference in amplitude
      or frequency of synaptic events in control and Mg2+-free solutions, indicating
      that the AMPA receptor plays an important role in regulating the inhibitory
      release of GABA within the SCN. Ipsi- and contralateral stimulation of the SCN
      consistently evoked excitatory synaptic responses. Inhibitory synaptic responses
      occurred in some neurons upon increasing stimulus strength. In conclusion, this
      study shows that there is a substantial influence from spontaneous glutamatergic
      synapses on the ventral part of the SCN and that these exhibit daily variations
      in activity. Diurnal fluctuations in spontaneous excitatory postsynaptic activity
      within this network may contribute to the mechanisms for synchronization of
      rhythms between individual SCN neurons and may underlie the daily variations in
      the spontaneous firing frequency of SCN neurons.

PMID- 11837949
TI  - Circadian organization in a diurnal rodent, Arvicanthis ansorgei Thomas 1910:
      chronotypes, responses to constant lighting conditions, and photoperiodic
      changes.
AB  - Little information is available on circadian organization in diurnal mammals. In
      the present study, the daily patterns of wheel-running activity were described in
      a diurnal rodent, Arvicanthis ansorgei Thomas 1910, as assessed by karyological
      analysis. Among 108 animals born in the colony and studied under a 12:12 light
      dark cycle (lights on at 7:00 a.m.), the authors determined the timing of daily
      activity (i.e., mean onsets and offsets of pattern of locomotor activity) and the
      level of wheel-running activity performed during daytime versus nighttime. The
      activity pattern was essentially diurnal in 84% of individuals, 46% being active
      only during the light period +/- 1 h (activity onsets and offsets at 6:20 a.m.
      and 7:40 p.m., respectively) and 38% being diurnal with a period of nocturnal
      activity longer than 1 h (activity onsets and offsets at 5:40 a.m. and 9:30 p.m.,
      respectively). Of the 108 animals, 16% expressed a nocturnal activity with
      diurnal overlaps no longer than 1 h. In 6 diurnal individuals first exposed to
      constant light and then to constant dim red light, the endogenous period was
      shortened from 24.6 +/- 0.1 to 24.0 +/- 0.1 h, respectively. The numbers of wheel
      revolutions per day and during the active period remained unchanged between the
      two lighting conditions. In response to different photoperiodic changes from
      16:08 to 08:16 light-dark cycles, the phase angle of photic synchronization,
      estimated by the daily onset of wheel-running activity in 6 diurnal animals,
      showed marked changes, its timing occurring 2 h before and 0.5 h after the onset
      of light under short and long photoperiods, respectively. The numbers of wheel
      revolutions per 24 h and during the active period were modified similarly
      according to photoperiodic changes. Finally, in 5 diurnal animals exposed to a
      12:12 light-dark cycle, the daily pattern of general locomotor activity,
      determined by telemetry, was not modified by wheel availability. The data
      indicate that A. ansorgei is an interesting experimental model to understand the
      regulation of the circadian timing system in day-active species.

PMID- 11837950
TI  - Photoperiod, reproduction, and immunity in select strains of inbred mice.
AB  - The purpose of this study was to determine whether decreased day lengths affect
      reproduction or the immune system in inbred mice. Irrespective of a nocturnal
      pineal melatonin rise, the signal for day length information, body and testis
      weights were the same in various strains 8 weeks after transfer from long to
      short days (16 to 8 h of light/day) compared to mice that remained in long days.
      Serum testosterone was unaffected by the photoperiod shift. The second goal was
      to determine whether the shift from long to short days influenced lymphocyte
      populations in spleen or blood, as well as innate and cell-mediated immune cell
      functions in C3H/HeN mice, an inbred strain with a robust melatonin rhythm. By
      flow cytometry, a stable percentage and number of B cells, T cells, and natural
      killer cells were identified in spleen from mice in both long and short days
      during the day and night. This complement of immunophenotypes in spleen suggests
      that equivalent functional capabilities persist in secondary lymphoid tissue of
      mice irrespective of day length. This was supported by findings that cytolytic
      activity by splenic natural killer cells (innate immunity) and antigen-induced T
      cell-dependent B cell antibody production (adaptive immunity) were similar in
      mice in long and short days. In blood, cell numbers but not helper T cell subset
      percentages (i.e., naive, memory, cytotoxic, or activated) were augmented in mice
      in short compared to long days, a consequence of increased circulating B cells.
      Day length differences in certain immunophenotypes in circulation may forecast
      photoperiod-mediated alterations in responsiveness to pathogens that are
      associated with a change in season. At night, the reduced proportion of cytotoxic
      T cells (long and short days), as well as increases in the percentage of
      activated T cells (long days), B cells (short days), and NK cell activity (long
      and short days) relative to daytime, suggests that surveillance and function by
      select immunophenotypes may adapt to circadian transitions even in highly inbred
      species. Thus, inbred mice retain capabilities for photoperiod to influence trait
      specific aspects of immune cell but not reproductive function.

PMID- 11837951
TI  - A model for "splitting" of running-wheel activity in hamsters.
AB  - Splitting of locomotor activity rhythm in hamsters occurs when the animals are
      exposed for several weeks to constant light. The authors propose a mathematical
      model that explains splitting in terms of a switch in the sign of coupling of two
      oscillators, from positive to negative, due to long-term exposure to constant
      light. The model assumes that the two oscillators are not identical and that the
      negative coupling strengths achieved by each individual animal are variable. With
      these assumptions, the model provides a unified picture of all different
      splitting patterns presented by the hamsters, provides an explanation for why the
      two activity components cross each other during many patterns, and explains why
      the phase difference achieved by the split components is often near 180 degrees.

PMID- 11837952
TI  - Bright-light mask treatment of delayed sleep phase syndrome.
AB  - We treated delayed sleep phase syndrome (DSPS) with an illuminated mask that
      provides light through closed eyelids during sleep. Volunteers received either
      bright white light (2,700 lux, n = 28) or dim red light placebo (0.1 lux, n = 26)
      for 26 days at home. Mask lights were turned on (< 0.01 lux) 4 h before arising,
      ramped up for 1 h, and remained on at full brightness until arising. Volunteers
      also attempted to systematically advance sleep time, avoid naps, and avoid
      evening bright light. The light mask was well tolerated and produced little sleep
      disturbance. The acrophase of urinary 6-sulphatoxymelatonin (6-SMT) excretion
      advanced significantly from baseline in the bright group (p < 0.0006) and not in
      the dim group, but final phases were not significantly earlier in the bright
      group (ANCOVA ns). Bright treatment did produce significantly earlier phases,
      however, among volunteers whose baseline 6-SMT acrophase was later than the
      median of 0602 h (bright shift: 0732-0554 h, p < 0.0009; dim shift: 0746-0717 h,
      ns; ANCOVA p = 0.03). In this subgroup, sleep onset advanced significantly only
      with bright but not dim treatment (sleep onset shift: bright 0306-0145 h, p <
      0.0002; dim 0229-0211 h, ns; ANCOVA p < .05). Despite equal expectations at
      baseline, participants rated bright treatment as more effective than dim
      treatment (p < 0.04). We conclude that bright-light mask treatment advances
      circadian phase and provides clinical benefit in DSPS individuals whose initial
      circadian delay is relatively severe.

PMID- 11837953
TI  - Modification of sonic boom wave forms during propagation from the source to the
      ground.
AB  - A number of physical processes work to modify the shape of sonic boom wave forms
      as the wave form propagates from the aircraft to a receiver on the ground. These
      include frequency-dependent absorption, nonlinear steepening, and scattering by
      atmospheric turbulence. In the past two decades, each of these effects has been
      introduced into numerical prediction algorithms and results compared to
      experimental measurements. There is still some disagreement between measurements
      and prediction, but those differences are now in the range of tens of percent.
      The processes seem to be understood. The present understanding of sonic boom
      evolution will be presented along with experimental justification.

PMID- 11837956
TI  - A model experiment to study sonic boom propagation through turbulence. Part III:
      validation of sonic boom propagation models.
AB  - In previous papers, we have shown that model experiments are successful in
      simulating the propagation of sonic booms through the atmospheric turbulent
      boundary layer. The results from the model experiment, pressure wave forms of
      spark-produced N waves and turbulence characteristics of the plane jet, are used
      to test various sonic boom models for propagation through turbulence. Both wave
      form distortion models and rise time prediction models are tested. Pierce's model
      [A. D. Pierce, "Statistical theory of atmospheric turbulence effects on sonic
      boom rise times," J. Acoust. Soc. Am. 49, 906-924 (1971)] based on the wave front
      folding mechanism at a caustic yields an accurate prediction for the rise time of
      the mean wave form after propagation through the turbulence.

PMID- 11837954
TI  - Propagation of finite amplitude sound through turbulence: modeling with
      geometrical acoustics and the parabolic approximation.
AB  - Sonic boom propagation can be affected by atmospheric turbulence. It has been
      shown that turbulence affects the perceived loudness of sonic booms, mainly by
      changing its peak pressure and rise time. The models reported here describe the
      nonlinear propagation of sound through turbulence. Turbulence is modeled as a set
      of individual realizations of a random temperature or velocity field. In the
      first model, linear geometrical acoustics is used to trace rays through each
      realization of the turbulent field. A nonlinear transport equation is then
      derived along each eigenray connecting the source and receiver. The transport
      equation is solved by a Pestorius algorithm. In the second model, the KZK
      equation is modified to account for the effect of a random temperature field and
      it is then solved numerically. Results from numerical experiments that simulate
      the propagation of spark-produced N waves through turbulence are presented. It is
      observed that turbulence decreases, on average, the peak pressure of the N waves
      and increases the rise time. Nonlinear distortion is less when turbulence is
      present than without it. The effects of random vector fields are stronger than
      those of random temperature fields. The location of the caustics and the
      deformation of the wave front are also presented. These observations confirm the
      results from the model experiment in which spark-produced N waves are used to
      simulate sonic boom propagation through a turbulent atmosphere.

PMID- 11837957
TI  - Atmospheric turbulence conditions leading to focused and folded sonic boom wave
      fronts.
AB  - The propagation and subsequent distortion of sonic booms with rippled wave fronts
      are investigated theoretically using a nonlinear time-domain finite-difference
      scheme. This work seeks to validate the rippled wave front approach as a method
      for explaining the significant effects of turbulence on sonic booms [A. S. Pierce
      and D. J. Maglieri, J. Acoust. Soc. Am. 51, 702-721 (1971)]. A very simple
      description of turbulence is employed in which velocity perturbations within a
      shallow layer of the atmosphere form strings of vortices characterized by their
      size and speed. Passage of a steady-state plane shock front through such a vortex
      layer produces a periodically rippled wave front which, for the purposes of the
      present investigation, serves as the initial condition for a finite-difference
      propagation scheme. Results show that shock strength and ripple curvature
      determine whether ensuing propagation leads to wave front folding. High
      resolution images of the computed full wave field provide insights into the
      spiked and rounded features seen in sonic booms that have propagated through
      turbulence.

PMID- 11837958
TI  - State of the art of sonic boom modeling.
AB  - Based on fundamental theory developed through the 1950s and 1960s, sonic boom
      modeling has evolved into practical tools. Over the past decade, there have been
      requirements for design tools for an advanced supersonic transport, and for tools
      for environmental assessment of various military and aerospace activities. This
      has resulted in a number of advances in the understanding of the physics of sonic
      booms, including shock wave rise times, propagation through turbulence, and
      blending sonic boom theory with modern computational fluid dynamics (CFD)
      aerodynamic design methods. This article reviews the early fundamental theory,
      recent advances in theory, and the application of these advances to practical
      models.

PMID- 11837959
TI  - Review and status of sonic boom penetration into the ocean.
AB  - Since the 1970 Sonic Boom Symposium, held at the ASA's 80th meeting in Houston,
      TX, substantial progress has been made in understanding the penetration of sonic
      booms into the ocean. The state of the art at that time was documented by J. C.
      Cook, T. Goforth, and R. K. Cook [J. Acoust. Soc. Am. 51, 729-741 (1972)]. Since
      then, additional experiments have been performed which corroborate Cook's and
      Sawyers' theory for sonic boom penetration into a flat ocean surface. In
      addition, computational simulations have validated that theory and extended the
      work to include arbitrarily shaped waveforms penetrating flat ocean surfaces.
      Further numerical studies have investigated realistic ocean surfaces including
      large-scale ocean swell. Research has also been performed on the effects of ocean
      inhomogeneities due to bubble plumes. This paper provides a brief overview of
      these developments.

PMID- 11837960
TI  - Validation of sonic boom propagation codes using SR-71 flight test data.
AB  - The results of two sonic boom propagation codes, ZEPHYRUS (NASA) and BOOM
      (TsAGI), are compared with SR-71 flight test data from 1995. Options available in
      the computational codes are described briefly. Special processing methods are
      described which were applied to the experimental data. A method to transform
      experimental data at close ranges to the supersonic aircraft into initial data
      required by the codes was developed; it is applicable at any flight regime. Data
      are compared in near-, mid-, and far fields. The far-field observation aircraft
      recorded both direct and reflected waves. Comparison of computed and measured
      results shows good agreement with peak pressure, duration, and wave shape for
      direct waves, thus validating the computational codes.

PMID- 11837961
TI  - An analysis of the response of Sooty Tern eggs to sonic boom overpressures.
AB  - It has been proposed that sonic booms caused a mass hatching failure of Sooty
      Terns in the Dry Tortugas in Florida by cracking the eggshells. This paper
      investigates this possibility analytically, complementing previous empirical
      studies. The sonic boom is represented as a plane-wave excitation with an N-wave
      time signature. Two models for the egg are employed. The first model, intended to
      provide insight, consists of a spherical shell, with the embryo represented as a
      rigid, concentric sphere and the albumen as an acoustic fluid filling the
      intervening volume. The substrate is modeled as a doubling of the incident
      pressure. The second, numerical model includes the egg-shape geometry and air
      sac. More importantly, the substrate is modeled as a rigid boundary of infinite
      extent with acoustic diffraction included. The peak shell stress, embryo
      acceleration, and reactive force are predicted as a function of the peak sonic
      boom overpressure and compared with damage criteria from the literature. The
      predicted peak sonic boom overpressure necessary for egg damage is much higher
      than documented sonic boom overpressures, even for extraordinary operational
      conditions. Therefore, as with previous empirical studies, it is concluded that
      it is unlikely that sonic boom overpressures damage avian eggs.

PMID- 11837962
TI  - Sonic booms of space shuttles approaching Edwards Air Force Base, 1988-1993.
AB  - From 1988 to 1993 13 sonic booms of space shuttles approaching Edwards Air Force
      Base were measured at a site 10 miles west of EAFB, with one to seven different
      sound level meters for each measurement. Results from five of these measurements
      are here presented. Maximum differences in measured levels between instruments
      for the same flight varied from 0 to 6 dB depending on the measurement descriptor
      and model of sound level meter. The average difference between predicted and
      measured values was 0.7+/-1.5 dB. For sound level meters with adequate bandwidth
      the waveforms measured varied from a near perfect N-wave to a more distorted form
      reflecting the influence of the varying condition of the atmosphere during
      propagation to the ground.

PMID- 11837963
TI  - Relative rates of growth of annoyance of impulsive and non-impulsive noises.
AB  - Twenty-nine people judged the relative annoyance of five variable level signals
      and 29 impulsive and non-impulsive fixed-level signals in an adaptive paired
      comparison study. Signals were presented for judgment as heard indoors in a
      facility capable of accurately reproducing the very low-frequency content of
      sonic booms. When the annoyance of sonic booms unaccompanied by rattle was
      compared with that of sounds containing more higher-frequency energy (an aircraft
      flyover and an octave band of noise centered at 1 kHz), the relative rate of
      growth of annoyance, as expressed in C-weighted SEL units, was nearly 2:1. In
      other words, to maintain subjective equality of annoyance, each increase in level
      of sonic booms had to be matched by nearly twice the increase in level of an
      aircraft flyover or an octave band of noise centered at 1 kHz. Relative rates of
      growth of annoyance of sonic booms accompanied by rattle and of non-impulsive
      sounds, including both low- (63-Hz octave band of noise) and high-frequency
      energy (1-kHz octave band of noise and an aircraft flyover), were closer to 1:1.
      Relative rates of growth of annoyance for sonic booms unaccompanied by rattle and
      low-frequency sounds (63 Hz) were also about 1:1. These differences in relative
      rates of growth of annoyance of impulsive and non-impulsive sounds are as
      plausibly attributed to their relative low-frequency content as to impulsiveness
      per se. It may therefore be more useful for some purposes to express the
      annoyance of impulsive signals and other environmental noises containing
      substantial low-frequency energy in terms of effective (duration-corrected)
      loudness level rather than commonplace ASEL or CSEL.

PMID- 11837964
TI  - Summary of recent NASA studies of human response to sonic booms.
AB  - NASA Langley Research Center has conducted three groups of studies on human
      response to sonic booms: laboratory, "inhome," and field. The laboratory studies
      were designed to: (1) quantify loudness and annoyance response to a wide range of
      shaped sonic boom signatures and (2) assess several noise descriptors as
      estimators of sonic boom subjective effects. The studies were conducted using a
      sonic boom simulator capable of generating and playing, with high fidelity, both
      user-prescribed and recorded boom waveforms to test subjects. Results showed that
      sonic boom waveform shaping provided substantial reductions in loudness and
      annoyance and that perceived level was the best estimator of subjective effects.
      Booms having asymmetrical waveforms were found to be less loud than symmetrical
      waveforms of equivalent perceived level. Subjective responses to simulated ground
      reflected waveforms were fully accounted for by perceived level. The inhome study
      presented participants with simulated sonic booms played within their normal home
      environment. The results showed that the equal energy theory of annoyance applied
      to a variety of multiple sonic boom exposures. The field studies concluded that
      sonic boom annoyance is greater than that in a conventional aircraft noise
      environment with the same continuous equivalent noise exposure.

PMID- 11837965
TI  - Effects of sonic booms on breeding gray seals and harbor seals on Sable Island,
      Canada.
AB  - The Concorde produces audible sonic booms as it passes 15 km north of Sable
      Island, Nova Scotia, where gray and harbor seals occur year round. The purpose of
      this research was to assess how sonic booms affect these seals. The intensity of
      the booms was measured and three types of data (beach counts, frequency of
      behavior, and heart rate) were collected before and after booms during the
      breeding seasons of the two species. In addition to the data taken during
      breeding, beach counts were made before and after booms during the gray seal
      moult. The greatest range in overpressure within a single boom was 2.70 psf
      during gray seal breeding and 2.07 psf during harbor seal breeding. No
      significant differences were found in the behavior or beach counts of gray seals
      following sonic booms, regardless of the season. Beach counts and most behaviors
      of harbor seals also did not differ significantly following booms, however,
      harbor seals became more vigilant. The heart rates of four gray seal mothers and
      three pups showed no clear change as a result of booms, but six male harbor seals
      showed a nonsignificant tendency toward elevated heart rates during the 15-s
      interval of the boom. These results suggest sonic booms produced by the Concorde,
      in level flight at altitude and producing on average a sonic boom of 0.9 psf, do
      not substantially affect the breeding behavior of gray or harbor seals.

PMID- 11837966
TI  - The effect of a coastline on the underwater penetration of sonic booms.
AB  - A simplified analysis is presented for the underwater noise levels from a steady
      supersonic flight traversing a coastline. The effect of the coast is to introduce
      a propagating noise component that does not exhibit the classic evanescent
      attenuation with depth for flights subsonic in water. Expressions are given to
      estimate the boundary of, and levels within, the coastal region where this
      component dominates. An illustrative example is presented.

PMID- 11837967
TI  - Seismic detection of sonic booms.
AB  - The pressure signals from a sonic boom will produce a small, but detectable,
      ground motion. The extensive seismic network in southern California, consisting
      of over 200 sites covering over 50000 square kilometers, is used to map primary
      and secondary sonic boom carpets. Data from the network is used to analyze three
      supersonic overflights in the western United States. The results are compared to
      ray-tracing computations using a realistic model of the stratified atmospheric at
      the time of the measurements. The results show sonic boom ground exposure under
      the real atmosphere is much larger than previously expected or predicted by ray
      tracing alone. Finally, seismic observations are used to draw some inferences on
      the origin of a set of "mystery booms" recorded in 1992-1993 in southern
      California.

PMID- 11837968
TI  - Acoustic propagation and atmosphere characteristics derived from infrasonic waves
      generated by the Concorde.
AB  - Infrasonic signals generated by daily supersonic Concorde flights between North
      America and Europe have been consistently recorded by an array of microbarographs
      in France. These signals are used to investigate the effects of atmospheric
      variability on long-range sound propagation. Statistical analysis of wave
      parameters shows seasonal and daily variations associated with changes in the
      wind structure of the atmosphere. The measurements are compared to the
      predictions obtained by tracing rays through realistic atmospheric models.
      Theoretical ray paths allow a consistent interpretation of the observed wave
      parameters. Variations in the reflection level, travel time, azimuth deviation
      and propagation range are explained by the source and propagation models. The
      angular deviation of a ray's azimuth direction, due to the seasonal and diurnal
      fluctuations of the transverse wind component, is found to be approximately 5
      degrees from the initial launch direction. One application of the seasonal and
      diurnal variations of the observed phase parameters is the use of ground
      measurements to estimate fluctuations in the wind velocity at the reflection
      heights. The simulations point out that care must be taken when ascribing a phase
      velocity to a turning height. Ray path simulations which allow the correct
      computation of reflection heights are essential for accurate phase
      identifications.

PMID- 11837969
TI  - Application of a hydrodynamic model to microencapsulation by coacervation.
AB  - The role of the hydrodynamic conditions in determining the characteristics of
      microcapsules made by coacervation was investigated in this study. The model
      proposed by Armenante and Kirwan, regarding the mass transfer to microcapsules in
      a turbulent agitated system, was applied. The working hypothesis was that the
      microcapsules are formed in microeddies generated by the agitation source. The
      dimensions of the microeddies, calculated in the vicinity of the agitation source
      according to Armenante and Kirwan, depend on the physical properties of the
      liquid medium and are inversely proportional to the power exchanged from the
      agitation source of the system. The power was determined according to the
      hydrodynamic rules developed by Rushton et al. The experimental results confirmed
      the hypothesis of the model. Indeed, a good relationship was found between the
      calculated size of the microeddies and the measured diameter of the
      microcapsules. Moreover, the distribution error (the standard deviation of the
      microcapsule size frequency distribution curve) was found to be proportional to
      the mean diameter value of the microcapsules and microeddies. This can be
      explained considering that the microeddies diameter increases by moving away from
      the agitation source and, consequently, a distribution of microeddies of
      difference sizes is present in the medium. The distribution error, which
      represents the difference between the smaller and the larger diameters, is
      inversely proportional to the exchanged power and, consequently, proportional to
      the mean diameter.

PMID- 11837970
TI  - In vitro antibiotic release from poly(3-hydroxybutyrate-co-3-hydroxyvalerate)
      rods.
AB  - Provision and maintenance of adequate concentrations of antibiotics at infection
      sites is very important in treating highly resistant infections. For diseases
      like implant related osteomyelitis (IRO) it is best to provide this locally via
      implanted drug formulations, as systemic administration of the antibiotic may not
      be effective due to damaged vasculature. In this study, poly(3-hydroxybutyrate-co
      3-hydroxyvalerate) (PHBV) rods containing 7, 14 and 22% (mol) 3-hydroxyvalerate
      were loaded with sulbactam:cefoperazone or gentamicin, and their antibiotic
      release behaviours were studied under in vitro conditions in physiological
      phosphate buffer at room temperature. The release patterns were representative of
      release from monolithic devices where a rapid early release phase is followed by
      a slower and prolonged release. With PHBV 22 rods, the latter phase continued for
      approximately 2 months. This duration is critical because a proper antibiotic
      therapy of IRO requires the minimal effective concentration for at least 6 weeks.
      After in vitro release, voids with sharp edges were detected on the rods,
      indicating that the drug crystals dissolved but the polymer did not undergo
      erosion within this test period. Changing the polymer:drug ratio from 2:1 to 20:1
      substantially decreased the drug release rate. A change of polymer type, however,
      did not lead to any detectable changes in the release patterns. Gentamicin
      release also followed a similar pattern, except that the concentration of the
      drug in the release medium exhibited a decrease after long release periods,
      indicating degradation (or decomposition) of the antibiotic in the release
      medium.

PMID- 11837971
TI  - Spray-dried microparticulate systems containing acetaminophen.
AB  - The present work investigates the preparation and the release of acetaminophen
      from spray-dried microparticles. Two cellulose derivatives were tested as
      sustaining agents: microcrystalline cellulose (MCC) and sodium
      carboxymethylcellulose (NaCMC). In-vitro dissolution studies were carried out in
      dissolution media of different pH. With MCC, the adsorption of acetaminophen on
      the surface or in the pores of the polymer does not allow a significant sustained
      release of the drug, which completely dissolves in 1 h. Conversely, the use of
      NaCMC retards the release of acetaminophen over a period of 6-8 h. The drug
      release depends on the plasticizer used and on the pH of the dissolution medium,
      and the mechanism consists essentially in the diffusion of the drug through the
      swollen polymeric matrix. The pH dependence observed can be correlated with a
      lower hydrophylicity of the polymer in acidic medium, which retards gel
      formation.

PMID- 11837972
TI  - Crosslinked chitosan microspheres for encapsulation of diclofenac sodium: effect
      of crosslinking agent.
AB  - Microspheres of chitosan crosslinked with three different crosslinking agents
      viz, glutaraldehyde, sulphuric acid and heat treatment have been prepared to
      encapsulate diclofenac sodium (DS). Chitosan microspheres are produced in a w/o
      emulsion followed by crosslinking in the water phase by one of the crosslinking
      methods. Encapsulation of DS has been carried out by soaking the already swollen
      crosslinked microspheres in a saturated solution of DS. Microspheres are further
      characterized by FTIR, x-RD and SEM. The in-vitro release studies are performed
      in 7.4 pH buffer solution. Microspheres produced are spherical and have smooth
      surfaces, with sizes ranging between 40-230 microm, as evidenced by SEM. The
      crosslinking of chitosan takes place at the free amino group in all the cases, as
      evidenced by FTIR. This leads to the formation of imine groups or ionic bonds.
      Polymer crystallinity increases after crosslinking, as determined by x-RD. The
      method adopted for drug loading into the microspheres is satisfactory, and up to
      28-30% w/w loading is observed for the sulphuric acid-crosslinked microspheres,
      whereas 23-29 and 15-23% of loadings are obtained for the glutaraldehyde (GA)-
      and heat-crosslinked microspheres, respectively. Among all the systems studied,
      the 32% GA crosslinked microspheres have shown the sloxvest release i.e. 41% at
      420 min, and a fastest release of 81% at 500 min is shown by heat crosslinking
      for 3 h. Drug release from the matrices deviates slightly from the Fickian
      process.

PMID- 11837973
TI  - Oxidation of linoleic acid encapsulated with gum arabic or maltodextrin by spray
      drying.
AB  - Linoleic acid was emulsified with gum arabic or maltodextrin at various weight
      ratios of the acid to the polysaccharide in the presence or absence of a small
      molecule emulsifier. The emulsions were spray-dried to produce microcapsules.
      Emulsions prepared with gum arabic were smaller in droplet size and more stable
      than those prepared with maltodextrin, and linoleic acid in a gum arabic-based
      microcapsule was also most resistant to oxidation than that in a maltodextrin
      based microcapsule. Although the oil droplet size in the emulsion with
      maltodextrin decreased and the emulsion stability was improved by addition of a
      small-molecule emulsifier to linoleic acid, the oxidative stability of the
      encapsulated linoleic acid was not significantly improved. Encapsulated linoleic
      acid of small droplet size oxidized more slowly than that of large droplet size.

PMID- 11837974
TI  - The release of diazepam from poly(hydroxybutyrate-hydroxyvalerate) microspheres.
AB  - Microspheres based on a poly(hydroxybutyrate-hydroxyvalerate) copolymer (PHBV)
      (Mw = 630kD, 21% mol HV) were loaded with diazepam using different emulsion
      solvent evaporation processes. Gelatin was used as a strategy to alter the
      release profile of the incorporated drug. The mean diameter of microspheres was
      from 30-40 micron. Drug-release from the microspheres over a 30-day period showed
      a characteristic triphasic release pattern with an initial burst effect, but was
      linear over the same period and without a burst effect when gelatin was used as a
      coating agent. Scanning electron microscopy revealed that the microspheres had
      different structures depending upon their method of preparation.

PMID- 11837975
TI  - Vibrio cholerae-loaded poly(DL lactide co-glycolide) microparticles.
AB  - Vibrio cholerae (VC)-loaded microparticles were prepared using poly(DL lactide-co
      glycolide) with a water-in-oil-in-water emulsion/solvent extraction technique.
      Particle characteristics including size distribution, VC-loading efficiencies,
      and in-vitro release pattern were investigated. The dispersed phase was PLG
      dissolved in dichloromethane, and the continuous phase was water containing PVP
      as a stabilizer with varied sodium chloride concentrations. VC was successfully
      entrapped in the microparticles with trapping efficiencies up to 97.8%, a loading
      level of 55.4 g/mg, and particle size of 3.8 microm. Using 10% w/v PVP with 5%
      w/v NaCl in the continuous phase resulted in a higher loading level (55.4 +/- 6.9
      g/mg), loading efficiency (97.8%), core region content (25.7 +/- 1.9 g/mg) and
      lower surface content (6.2 +/- 0.9 g/mg) than without NaCl (loading content: 40.7
      +/- 5.1 g/mg; loading efficiency 52.1%; core region content: 8.3 +/- 0.5 g/mg;
      surface content: 19.5 +/- 1.1 g/mg). A linear release profile from VC-loaded
      microparticles was found. A preliminary animal oral administration study
      indicated that the VC-loaded microparticles, as an oral delivery system, have
      shown effective immunogencity in rats for 2 months. The VC incorporation and
      physicochemical characterization data obtained in this study may be relevant in
      optimising the vaccine incorporation and delivery properties of these potential
      vaccine targeting carriers.

PMID- 11837976
TI  - Specific attachment of aqueous-based microcapsules to macrophages, B cells, and
      dendritic cells in vitro.
AB  - Microcapsules were previously prepared composed of aqueous anionic polymers (e.g.
      alginate) and aqueous amines (e.g. spermine) and it was found that the aqueous
      based microcapsules enhanced rotavirus-specific immune responses after oral or
      parenteral immunization of mice. In these studies, one has modified the amine
      moiety of aqueous-based microcapsules to bind covalently to avidin and the avidin
      bearing microcapsules were linked to biotinylated antibodies specific for surface
      markers on murine macrophages, dendritic cells, or B cells. Using fluorescence
      flow cytometry, it was found that antibody-coated microcapsules bound
      specifically to antigen-presenting cells (APC) in vitro. The availability of APC
      specific microcapsules should allow for the uptake of antigens by specific APC,
      and further one's understanding of the relative capacities of different APC to
      induce antigen-specific immune responses.

PMID- 11837977
TI  - The effect of oral absorption enhancers on the in vivo performance of insulin
      loaded poly(ethylcyanoacrylate) nanospheres in diabetic rats.
AB  - Poly(ethylcyanoacrylate) (PECA) nanospheres have been employed as biodegradable
      polymeric carriers for oral (po) delivery of insulin. The main goal of this
      investigation was to screen various absorption enhancers, which were used to
      protect insulin-loaded PECA, by following their in vivo performance after oral
      administrations to streptozotocin-induced diabetic rats. The nanospheres were
      prepared by polymerization in a continuous aqueous phase at pH 2.5 and in the
      presence of Pluronic 68 (0.5%). This polymerization technique was able to hold 85
      +/- 7.5% of insulin added, 30 min after initiation of polymerization. The drug
      loading was evaluated by HPLC. Insulin absorption after oral administration was
      evaluated by its hypoglycemic effect. The addition of protease inhibitor to
      insulin-loaded PECA nanospheres significantly reduced the blood glucose level
      after po administrations. Capric acid (0.5%) showed the maximum reduction in
      blood glucose level (bG max = 34.4 +/- 4.1 mg%), while cholic acid (0.5%) showed
      the fastest reduction in blood glucose level (Tmax, G = 6.0 +/- 0.2 h) among the
      tested oral absorption enhancers. Insulin associated with PECA nanospheres
      retained its biological activity up to 12 days in 50% of the rats in the presence
      of glycyrrhizic acid (1%). The per cent pharmacological availabilities (PA%) were
      in the order of capric acid (0.5%) > glycyrrhizic acid (1%) > deoxycholic acid
      (0.5%) > hydroxypropyl-beta-cyclodextrin (HPbetaCD) (1%) > cholic acid (0.5%).
      There was no significant difference in the PA% between capric acid (0.5%),
      glycyrrhizic acid (1%) and deoxycholic acid (0.5%). Although sodium cholate
      (0.5%) showed the lowest increase in PA% (3.1 +/- 3.11%), its Tmax G was the
      shortest (6 +/- 0.2 h) among the tested absorption enhancers. The reduction in
      blood glucose levels was maintained < 200 mg/dL in the order of glycyrrhizic acid
      (166 +/- 56 h) > capric acid (72 h) >; deoxycholic acid (66 +/- 6 h) > no
      enhancer (64 +/- 16 h) > HPbetaCI) (31 +/- 17.5) > cholic acid (22 +/- 5.7 h) >
      aprotenin (20 +/- 3.5 h). Therefore, capric acid and glycyrrhizic acid could be
      successfully used as oral absorption enhancers.

PMID- 11837978
TI  - Preparation and stability of agarose microcapsules containing BCG.
AB  - An emulsification/internal gelation method of preparing small-sized agarose
      microcapsules containing Bacillus Calmette-Guerin (BCG) is reported. Agarose
      microcapsules have been prepared by the emulsification of the hydrogel within a
      vegetable oil followed by its gelation due to the cooling of the system. Four
      different oils (sesame, sweet almonds, camomile and jojoba) were assayed. The
      rheological analysis of the oils showed a Newtonian behaviour, with viscosity
      values of 37.7, 51.2, 59.3 and 67.1 mPa s for jojoba, camomile, sesame and sweet
      almonds oil, respectively. The particle size of the microcapsules obtained ranged
      from 23.1 microm for the microcapsules prepared with sweet almonds oil to 42.6
      microm for those prepared with jojoba. The microcapsule particle size was found
      to be dependent on the viscosity of the oil used in the emulsification step. The
      encapsulated BCG was identified by the Difco TB stain set K, followed by
      observation under optical microscopy. Once prepared, microcapsules were freeze
      dried using 5% trehalose as cryoprotectant and the stability of the microcapsules
      was assayed during 12 months storage at room temperature, observing that agarose
      microcapsules were stable after 12 months storage, since there was no evidence of
      alteration in the freeze-dried appearance, resuspension rate, observation under
      microscope, or particle size.

PMID- 11837979
TI  - Polyvinylamine hydrochloride-based microcapsules: polymer synthesis, permeability
      and mechanical properties.
AB  - Mechanically stable microcapsules, with sizes of 0.4-1.5 mm, have been produced
      with permeabilities appropriate for applications involving living cells and
      controlled delivery. Polyvinylamine hydrochloride was employed alone, in miXtures
      with poly(methylene-co-guanidine) hydrochloride, or as a coating material for pre
      formed capsules. The influence of polymer molar mass, the ratio between the two
      polycations, the coating time, and the capsule size on the properties of the
      capsules were analysed. The competitive displacement of one polycation with
      another in the polysaccharide matrix was also documented. The properties of the
      capsules vary remarkably, depending of the polyelectrolyte combinations used for
      their preparation. Specifically, capsules could withstand compressive loads of
      between 0.09-1.67 N, while the permeability varied from 10-120 kDa. Both are
      within the ranges required for clinical immunosuppressive therapies.

PMID- 11837980
TI  - Literature alerts.

PMID- 11837981
TI  - n-3 fatty acids and revascularization procedures.
AB  - Largely initiated by studies among Greenland Eskimos in the early 1970s, great
      attention has been given to the possible effects of the very long chain n-3
      polyunsaturated fatty acids (PUFA) in a variety of cardiovascular disease states.
      A series of possibly positive effects on pathogenetic mechanisms in
      cardiovascular disease has evolved from laboratory studies in cell cultures and
      animals as well as in humans, focusing mainly on eicosanoid metabolism with
      reduced activities of platelets and leucocytes, reduced plasma triglycerides and,
      antiarrhythmic effects in the myocardium. A rationale for a positive effect of
      very long chain n-3 PUFA in the secondary prophylaxis after revascularization
      procedures obviously also exists. The positive clinical effects based on
      prospectively randomized trials are summarized as follows. After coronary artery
      bypass grafting (CABG), the SHOT study showed statistically significant reduction
      in angiographic vein graft occlusion in 610 patients after 1 yr with
      supplementation of 3.4 g/d of highly concentrated very long chain n-3 PUFA. The
      reduction in occlusion rates was significantly related to the change in the n-3
      PUFA concentration in serum phospholipids during the study period with the
      occlusion rate in the upper quartile of such changes at only approximately 50% of
      that in the lower quartile. These results were also clearly related to the
      presence of angina pectoris and occurrence of myocardial infarction after 1 yr.
      Several studies were conducted in patients after percutaneous transluminal
      coronary angioplasty (PTCA). By 1993, two meta-analyses indicated a positive
      effect on the restenosis rate, a significant problem after otherwise successful
      PTCA. During the late 1990s, three large prospective randomized placebo
      controlled angiographic studies were conducted with very long n-3 PUFA 5.1-8.0
      g/d, all with completely negative results. Today, therefore, very long chain n-3
      PUFA supplementation cannot be recommended to reduce the incidence of restenosis
      after PTCA. All studies were performed without stenting of the coronary lesion.
      In the very special revascularization procedure of heart transplantation,
      evolving hypertension and accelerated atherosclerosis have been major clinical
      problems. In other studies, positive effects by supplementation with very long
      chain n-3 PUFA (3.4-5.7 g/d) were obtained on the surrogate end points coronary
      vasoreactivity to acetylcholine and hypertension, respectively. On the basis of
      the presently available literature from clinical studies, recommendations for
      supplementation with very long chain n-3 PUFA can be given to patients after
      venous CABG (up to 3.4 g/d), and after heart transplantation (3.4-5.7 g/d) but
      not to patients after traditional PTCA. In fact, data from substudies suggested
      the possibility that large doses (5.1 g/d) of very long chain n-3 PUFA might be
      contraindicated because they induce a proinflammatory state in patients under
      oxidative stress.

PMID- 11837983
TI  - Myocardial membrane fatty acids and the antiarrhythmic actions of dietary fish
      oil in animal models.
AB  - Epidemiologic studies, animal studies, and more recently, clinical intervention
      trials all suggest a role for regular intake of dietary fish oil in reducing
      cardiovascular morbidity and mortality. Prevention of cardiac arrhythmias and
      sudden death is demonstrable at fish or fish oil intakes that have little or no
      effect on blood pressure or plasma lipids. In animals, dietary intake of fish oil
      [containing both eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid
      (DHA, 22:6n-3)] selectively increases myocardial membrane phospholipid content of
      DHA, whereas low dose consumption of purified fatty acids shows antiarrhythmic
      effects of DHA but not EPA. Ventricular fibrillation induced under many
      conditions, including ischemia, reperfusion, and electrical stimulation, and even
      arrhythmias induced in vitro with no circulating fatty acids are prevented by
      prior dietary consumption of fish oil. The preferential accumulation of DHA in
      myocardial cell membranes, its association with arrhythmia prevention, and the
      selective ability of pure DHA to prevent ventricular fibrillation all point to
      DHA as the active component of fish oil. The antiarrhythmic effect of dietary
      fish oil appears to depend on the accumulation of DHA in myocardial cell
      membranes.

PMID- 11837982
TI  - The electrophysiologic basis for the antiarrhythmic and anticonvulsant effects of
      n-3 polyunsaturated fatty acids: heart and brain.
AB  - The n-3 polyunsaturated fatty acids (PUFA) have been shown to be antiarrhythmic
      in animals and probably in humans. PUFA stabilize the electrical activity of
      isolated cardiac myocytes by modulating sarcolemmal ion channels, so that a
      stronger electrical stimulus is required to elicit an action potential and the
      refractory period is markedly prolonged. Inhibition of voltage-dependent sodium
      currents, which initiate action potentials in excitable tissues, and of the L
      type calcium currents, which initiate release of sarcoplasmic calcium stores,
      thus increasing cytosolic free calcium concentrations and activating the
      contractile proteins in myocytes, appears at present to be the probable major
      antiarrhythmic mechanisms of PUFA. Because the ion channels in neurons have
      channel proteins essentially homologous to those in the heart, the n-3 fatty
      acids would appear to be likely to affect the electrical activity in the brain in
      a manner similar to their effects in the heart, and accumulating evidence
      supports this notion. Evidence of important beneficial neurological effects of
      dietary n-3 PUFA are emerging with more likely to be discovered.

PMID- 11837984
TI  - n-3 fatty acids and the risk of sudden cardiac death.
AB  - Sudden cardiac death (SCD) is a major cause of mortality in Western countries.
      Furthermore, SCD is often the first manifestation of coronary artery disease,
      making it difficult to prevent. Heart rate variability (HRV), which can be
      determined by extended recording of the heart rate by 24-h Holter monitoring, has
      been shown to be one of the best predictors of the risk of SCD. There is
      increasing evidence from animal experiments and clinical trials in humans that n
      3 fatty acids reduce the risk of SCD. We have studied the effect of n-3 fatty
      acids on HRV and present data clearly showing that n-3 fatty acids increase HRV.
      This adds further to the hypothesis that an increased intake of n-3 fatty acids
      may reduce the risk of SCD.

PMID- 11837985
TI  - Efficacy of n-3 polyunsaturated fatty acids after myocardial infarction: results
      of GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza
      nell'Infarto Miocardico.
AB  - Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardio (GISSI)
      Prevenzione was conceived as a population, pragmatic trial on patients with
      recent myocardial infarctions conducted in the framework of the Italian public
      health system. In GISSI-Prevenzione, patients were invited to follow
      Mediterranean dietary habits, and were treated with up-to-date preventive
      pharmacological interventions. Long-term n-3 PUFA (1 g daily) but not vitamin E
      (300 mg daily) was beneficial for death and for combined death, nonfatal
      myocardial infarction, and stroke. All the benefit, however, was attributable to
      the decrease in risk for overall, cardiovascular, cardiac, coronary, and sudden
      death. At variance with the orientation of a scientific scenario largely
      dominated by the "cholesterol-heart hypothesis," GISSI-Prevenzione results
      indicate n-3 PUFA (virtually devoid of any cholesterol-lowering effect) as a
      relevant pharmacological treatment for secondary prevention after myocardial
      infarction. As to the relevance and comparability of GISSI-Prevenzione results,
      up to 5.7 lives could be saved every 1000 patients with previous myocardial
      infarction treated with n-3 PUFA (1 g daily) per year. Such a result is
      comparable to that observed in the Long-Term Intervention with Pravastatin in
      Ischaemic Disease (LIPID) trial, where 5.2 lives could be saved per 1000
      hypercholesterolemic, coronary heart disease patients treated with pravastatin
      for 1 yr. The choice of a relatively low-dose regimen (1-g capsule daily) more
      acceptable for long-term treatment in a population of patients following
      Mediterranean dietary habits, and the pattern of effects seen in GISSI
      Prevenzione (namely, reduction of overall mortality with no decrease in the rate
      of nonfatal myocardial infarction) all strongly suggest that n-3 PUFA treatment
      should be considered a recommended new component of secondary prevention. The
      importance of this combined/additive effect is further suggested by the analyses
      of the interplay between diet and n-3 PUFA: There is an interesting direct
      correlation between size of the effect and "correctness" of background diets. It
      can be anticipated that a conceptual barrier must be overcome: A "dietary drug"
      should be added to "dietary advice," which remains fundamental to allow this
      statement to become true in clinical practice.

PMID- 11837986
TI  - n-3 polyunsaturated fatty acids and cardiovascular diseases.
AB  - An expert round table discussion on the relationship between intake of n-3
      polyunsaturated fatty acids (PUFA) mainly of marine sources and coronary heart
      disease at the 34th Annual Scientific Meeting of European Society for Clinical
      Investigation came to the following conclusions: 1. Consumption of 1-2 fish
      meals/wk is associated with reduced coronary heart disease (CHD) mortality. 2.
      Patients who have experienced myocardial infarction have decreased risk of total,
      cardiovascular, coronary, and sudden death by drug treatment with 1 g/d of
      ethylesters of n-3 PUFA, mainly as eicosapentaenoic acid (EPA) and
      docosahexaenoic acid (DHA). The effect is present irrespective of high or low
      traditional fish intake or simultaneous intake of other drugs for secondary CHD
      prevention. n-3 PUFA may also be given as fatty fish or triglyceride
      concentrates. 3. Patients who have experienced coronary artery bypass surgery
      with venous grafts may reduce graft occlusion rates by administration of 4 g/d of
      n-3 PUFA. 4. Patients with moderate hypertension may reduce blood pressure by
      administration of 4 g/d of n-3 PUFA. 5. After heart transplantation, 4 g/d of n-3
      PUFA may protect against development of hypertension. 6. Patients with
      dyslipidemia and or postprandial hyperlipemia may reduce their coronary risk
      profile by administration of 1-4 g/d of marine n-3 PUFA. The combination with
      statins seems to be a potent alternative in these patients. 7. There is growing
      evidence that daily intake of up to 1 energy% of nutrients from plant n-3 PUFA
      (alpha-linolenic acid) may decrease the risk for myocardial infarction and death
      in patients with CHD. This paper summarizes the conclusions of an expert panel on
      the relationship between n-3 PUFA and CHD. The objectives for the experts were to
      formulate scientifically sound conclusions on the effects of fish in the diet and
      the administration of marine n-3 PUFA, mainly eicosapentaenoic acid (EPA, 20:5n
      3) and docosahexaenoic acid (DHA, 22:6n-3), and eventually of plant n-3 PUFA,
      alpha-linolenic acid (ALA, 18:3n-3), on primary and secondary prevention of CHD.
      Fish in the diet should be considered as part of a healthy diet low in saturated
      fats for everybody, whereas additional administration of n-3 PUFA concentrates
      could be given to specific groups of patients. This workshop was organized on the
      basis of questions sent to the participants beforehand, on brief introductions by
      the participants, and finally on discussion and analysis by a group of
      approximately 40 international scientists in the fields of nutrition, cardiology,
      epidemiology, lipidology, and thrombosis.

PMID- 11837988
TI  - Short-term folic acid supplementation induces variable and paradoxical changes in
      plasma homocyst(e)ine concentrations.
AB  - Folic acid is presently the mainstay of treatment for most subjects with elevated
      plasma homocyst(e)ine concentrations [Plasma or serum homocyst(e)ine, or total
      homocysteine, refers to the sum of the sulfhydryl amino acid homocysteine and the
      homocysteinyl moieties of the disulfides homocystine and homocystein-cysteine,
      whether free or bound to plasma proteins.] Changes in homocyst(e)ine in response
      to folic acid supplementation are characterized by considerable interindividual
      variation. The purpose of this study was to identify factors that contribute to
      heterogeneity in short-term responses to folic acid supplementation. The effects
      of folic acid supplementation (1 or 2 mg per day) for 3 wk on plasma
      homocyst(e)ine concentrations were assessed in 304 men and women. Overall, folic
      acid supplementation increased mean plasma folate 31.5 +/- 98.0 nmol/L and
      decreased mean plasma homocyst(e)ine concentrations 1.2 +/- 2.4 micromol/L. There
      was evidence of substantial interindividual variation in the homocyst(e)ine
      response from -18.5 to +7.1 micromol/L, including an increase in homocyst(e)ine
      in 20% of subjects (mean increase 1.5 +/- 1.4 micromol/L). Basal homocyst(e)ine,
      age, male gender, cigarette smoking, use of multivitamins, methylene
      tetrahydrofolate reductase, and cystathionine beta-synthase polymorphisms
      accounted for 47.6% of the interindividual variability in the change in
      homocyst(e)ine after folic acid supplementation, but about 50% of variability in
      response to folic acid was not explained by the variables we studied.

PMID- 11837989
TI  - Homocysteine and atherothrombosis.
AB  - Atherosclerosis with or without thrombosis superimposed is the most frequent
      cause of ischemic heart disease (IHD), peripheral arterial disease, and a main
      cause of stroke. Conflicting results have been reported in genetic,
      observational, and experimental studies on the relationship between homocysteine
      and these atherothrombotic diseases. Although cardiovascular complications are
      common in homocystinuric patients (severe hyperhomocysteinemia), IHD, the most
      frequent manifestation of atherothrombosis in the general population, appears to
      be rare. On the basis of findings in individuals with hyperhomocysteinemia of
      genetic origin, there is in fact no clear evidence for a causal role of
      homocysteine in the pathogenesis of atherothrombotic disease, and the positive
      association between plasma homocysteine and IHD observed in many, but not all
      epidemiologic studies does not prove causality. To infer causality from
      observational studies, there should be a temporal, consistent, strong,
      independent, graded (dose-response effect), and duration-dependent relationship
      between exposure and outcomes, and a biologically plausible mechanism should
      exist. The relationship between plasma homocysteine levels and IHD does not
      fulfill these criteria beyond reasonable doubt. In the general population, plasma
      homocysteine levels are to a great extent determined by dietary habits, and
      plasma homocysteine could be a marker, or a consequence, of atherothrombosis
      and/or risk-associated behavior (e.g., a diet low in fruits and vegetables)
      rather than a cause of atherothrombosis. Experimentally, hyperhomocysteinemia is
      not in itself atherogenic in normal animals with relatively low plasma
      cholesterol levels. The homocysteine theory of atherosclerosis should be tested
      more thoroughly in hypercholesterolemic animals that develop atherosclerosis
      spontaneously to determine whether elevated plasma homocysteine levels are
      harmful under atherogenic conditions. A causal role of homocysteine in
      atherothrombotic disease remains to be established.

PMID- 11837987
TI  - Hyperhomocysteinemia and thrombosis.
AB  - Homocysteine (Hcy) is a sulfhydryl amino acid derived from the metabolic
      conversion of methionine, which is dependent on vitamins (folic acid, B12, and
      B6) as cofactors or cosubstrates. In 1969, McCully first reported the presence of
      severe atherosclerotic lesions in patients with severe hyperhomocysteinemia and
      hypothesized the existence of a pathogenic link between hyperhomocysteinemia and
      atherogenesis. Several case-control and cross-sectional studies were consistent
      with the initial hypothesis of McCully, showing that moderate
      hyperhomocysteinemia is also associated with heightened risk of occlusive
      arterial disease. Less consistent results have been reported by prospective
      cohort studies of subjects who were healthy at the time of their enrollment,
      whereas prospective cohort studies of patients with overt coronary artery disease
      or other conditions at risk consistently confirmed the association between
      moderate hyperhomocysteinemia and cardiovascular morbidity and mortality. More
      recently, an association between moderate hyperhomocysteinemia and heightened
      risk of venous thromboembolism has been documented, suggesting that
      hyperhomocysteinemia might be involved not only in atherogenesis, but also in
      thrombogenesis. The mechanisms by which hyperhomocysteinemia might contribute to
      atherogenesis and thrombogenesis are incompletely understood. The mainstay of
      treatment of hyperhomocysteinemia is folic acid, alone or in combination with
      vitamin B12 and vitamin B6. Although it is quite clear that vitamins effectively
      reduce the plasma levels of total homocysteine (tHcy), we do not yet know whether
      they will decrease the risk of vascular disease. The results of ongoing
      randomized, placebo-controlled, double-blind trials of the effects of vitamins on
      the thrombotic risk will help in defining whether the relationship between
      hyperhomocysteinemia and thrombosis is causal, and will potentially have a
      dramatic effect in the prevention of thromboembolic events.

PMID- 11837990
TI  - The Hordaland Homocysteine Studies.
AB  - The Hordaland Homocysteine Study is a population-based screening of total plasma
      homocysteine (tHcy) in approximately 18,000 men and women aged 40-67 yr that took
      place in 1992-1993 in the county of Hordaland in Western Norway. In this cohort,
      tHcy was associated with several physiologic and life-style factors, including
      age and gender, blood pressure, serum cholesterol, smoking, alcohol and coffee
      consumption, physical activity, diet, and vitamin status. All associations with
      established cardiovascular risk factors were in the direction expected to confer
      increased risk. In a subset of 5,883 women aged 40-42 yr, tHcy was associated
      with previous pregnancy outcomes, including preeclampsia, placental abruption,
      and neural tube defects. This article reviews the published results from the
      Hordaland Homocysteine Study in the light of relevant literature. The Hordaland
      Homocysteine cohort will be used for future investigations of the stability of
      tHcy and vitamin status over time, and to investigate associations with mortality
      and morbidity including cancer incidence.

PMID- 11837992
TI  - In vivo measurement of the redox state.
AB  - As part of an aerobic life, we oxidize a large pool of biomolecules to obtain
      chemical energy. During this process, several intermediates are formed; some are
      chemically unstable and are referred to as free radicals (FR). FR tend to react
      quickly with their surrounding biological environment; depending on the nature of
      the molecule attacked, different reactions can occur, i.e., lipid peroxidation,
      protein oxidation, or DNA oxidation products. As aerobic life has evolved,
      antioxidant defense systems against FR have developed. When an imbalance between
      production of FR (oxidants) and defense systems against them (antioxidants)
      happens, a situation of oxidative stress occurs. This can lead to irreversible
      biochemical changes, with subsequent tissue damage and disease. Establishing the
      involvement of FR in the pathogenesis of a disease has been difficult because of
      the lack of sensitive and specific methodology to detect them. No ideal
      biomarkers for in vivo FR-induced damage are available as yet. However, some
      reliable indices of FR formation are now available, and in some pathologic
      conditions, evidence is accumulating to show that FR damage might play a
      functional role. The task for the near future will be to try to simplify the
      analytical methodology and elucidate the molecular mechanisms underlying the
      formation, disposition, and kinetics of FR marker molecules.

PMID- 11837991
TI  - The oxidant stress hypothesis of atherogenesis.
AB  - Atherosclerosis is the commonest lesion of blood vessels and is responsible for
      life-threatening events such as myocardial infarction and stroke. In the last two
      decades a series of excellent studies unraveled biochemical mechanisms that
      provided the background for a theory of atherogenesis. This theory is centered on
      foam cells and on free radical-mediated modification of low density lipoprotein
      (LDL). Foam cells are the main cell type of atherosclerotic lesions and originate
      from monocytes migrated from blood and from smooth muscle cells of the arterial
      wall. Foam cells are engulfed of lipids taken from LDL. Paradoxically,
      accumulation of LDL in developing foam cells does not occur via the classic LDL
      receptor. Incubation of macrophages with even very high concentrations of LDL
      does not appreciably increase cholesterol content. Chemically modified LDL easily
      enter the cells of atherosclerotic plaque via an unregulated receptor, the
      scavenger receptor. The most studied chemical modification of LDL is that induced
      by free radicals.

PMID- 11837993
TI  - The role of antioxidants in the Mediterranean diet.
AB  - Traditional Mediterranean diets, as opposed to North European and American diets,
      include a significantly large amount of plant foods; this notable difference
      between the two eating styles, despite the similarities among other classic risk
      factors for coronary heart disease (CHD) such as high plasma cholesterol levels,
      has been associated with a lower risk of developing the CHD and certain cancers.
      The involvement of excessive free radical production and the great number of
      epidemiologic studies linking antioxidant intake with a reduced incidence of the
      above-mentioned diseases indicate that dietary antioxidants likely play a
      protective role. Because diets in the Mediterranean are (or better yet, were)
      characterized by abundant plant foods (fruits, vegetables, breads, nuts, seeds;
      wine and olive oil), this article includes a review of the potential activities
      of dietary antioxidants, which are plentiful in Mediterranean diets, and wine as
      related to human disease.

PMID- 11837995
TI  - Marine n-3 fatty acids: basic features and background.
AB  - There is some evidence from epidemiology that intake of n-3 polyunsaturated fatty
      acids (PUFA) from seafood may protect against coronary artery disease (CAD). This
      hypothesis is further supported from animal data showing a beneficial effect of n
      3 PUFA on thrombosis and atherosclerosis in animals fed fish oils in most, but
      not all, studies. There are several mechanisms by which an increased intake of
      marine n-3 PUFA may protect against CAD; the most universal finding is a
      reduction of plasma triglycerides. It is puzzling, however, that a very low
      amount of n-3 PUFA, with no known beneficial biochemical effects, seems to be
      cardioprotective. It has therefore been of paramount interest to perform clinical
      trials. Such evidence and trials are discussed in later chapters, and the results
      have been very encouraging.

PMID- 11837994
TI  - Antioxidant vitamins and prevention of cardiovascular disease: epidemiological
      and clinical trial data.
AB  - Naturally occurring antioxidants such as vitamin E, beta-carotene, and vitamin C
      can inhibit the oxidative modification of low density lipoproteins. This action
      could positively influence the atherosclerotic process and, as a consequence, the
      progression of coronary heart disease. A wealth of experimental studies provide a
      sound biological rationale for the mechanisms of action of antioxidants, whereas
      epidemiologic studies strongly sustain the "antioxidant hypothesis." To date,
      however, clinical trials with beta-carotene supplements have been disappointing,
      and their use as a preventive intervention for cancer and coronary heart disease
      should be discouraged. Only scanty data from clinical trials are available for
      vitamin C. As to vitamin E, discrepant results have been obtained by the Alpha
      Tocopherol, Beta Carotene Cancer Prevention Study with a low-dose vitamin E
      supplementation (50 mg/d) and the Cambridge Heart Antioxidant Study (400-800
      mg/d). The results of the GISSI-Prevenzione (300 mg/d) and HOPE (400 mg/d) trials
      suggest the absence of relevant clinical effects of vitamin E on the risk of
      cardiovascular events. Currently ongoing are several large-scale clinical trials
      that will help in clarifying the role of vitamin E in association with other
      antioxidants in the prevention of atherosclerotic coronary disease.

PMID- 11837996
TI  - n-3 fatty acids: antiatherosclerotic effects.
AB  - The low incidence of cardiovascular disease associated epidemiologically with
      high consumption of food rich in n-3 fatty acids suggests the possibility that
      part of the beneficial cardiovascular effects of these natural substances may be
      due to a reduction of atherosclerosis. This has been recently confirmed in
      autoptic data and in at least one prospective trial evaluating the progression of
      coronary atherosclerosis in humans. This paper reviews published literature on n
      3 fatty acids and atherosclerosis in animal models and in humans and in vitro
      experimental data yielding suport to the hypothesis of antiatherosclerotic
      effects of these substances.

PMID- 11837997
TI  - n-3 polyunsaturated fatty acids and coronary thrombosis.
AB  - Studies of Greenland Eskimos showed that a very high intake of marine n-3 fatty
      acids markedly inhibited platelet reactivity and suggested that intake of these
      fatty acids might prevent coronary thrombosis. Later studies with lower, more
      practical doses of n-3 fatty acids also have shown a platelet inhibitory effect
      of n-3 fatty acids, albeit fairly marginal. Furthermore, n-3 fatty acids have
      little effect on measures of blood coagulability and may slightly decrease
      fibrinolysis. In animal models, n-3 fatty acids often have been shown to inhibit
      thrombosis, but again the doses have tended to be very high. Finally, there has
      been little effect of (low-dose) n-3 fatty acids in clinical trials in humans on
      the incidence of myocardial infarction. Overall, there is little evidence for a
      major antithrombotic effect of practical doses of n-3 fatty acids on coronary
      thrombosis. This does not exclude a beneficial effect of n-3 fatty acids on
      coronary heart disease as suggested from clinical trials, but the major effect
      may be antiarrhythmic rather than antithrombotic.

PMID- 11837999
TI  - The effect of n-3 fatty acids on low density lipoprotein subfractions.
AB  - A predominance of small, dense low density lipoprotein (LDL) represents a
      significant source of increased risk for the development of coronary heart
      disease in Westernized countries. Dietary long-chain n-3 polyunsaturated fatty
      acids exert a potent triglyceride-lowering effect that redistributes LDL
      subfractions toward larger and lighter particles. These dietary fatty acids thus
      have a key role to play in providing protection against this particularly
      atherogenic type of LDL.

PMID- 11838001
TI  - Quality of reporting randomised clinical trials in dental and medical research.
AB  - OBJECTIVE: To assess 1) the quality of reporting randomised clinical trials in
      dental (RCT-Ds) and medical research (RCT-Ms), 2) the quality of RCT reports in
      relation to the journal impact factor, 3) the source of funding, and 4) the
      quality of RCT-Ds in different areas of dental research. DESIGN RANDOM: samples
      of 100 RCT-Ds and 100 RCT-Ms published in 1999 were evaluated for quality of
      reporting under blinded conditions with the Jadad quality assessment scale. In
      addition, correlation between the quality scores and journal impact factor or
      source of funding, as well as area of dental research were analysed. RESULTS: The
      quality of RCT-Ds and RCT-Ms published in 1999 was generally inadequate. The
      quality was largely equivalent in RCT-Ds and RCT-Ms. There was no correlation
      between the quality scores and the journal impact factor or the source of
      funding. Some differences were found in the quality scores between different
      areas of dental research. CONCLUSIONS: The results from these RCT-Ds and RCT-Ms
      show that most of them were imperfect in the reporting of methodology and trial
      conduct. There is a clear need to improve the quality of trial reporting in
      dental and medical research.

PMID- 11838000
TI  - The effect of n-3 fatty acids on coronary atherosclerosis: results from SCIMO, an
      angiographic study, background and implications.
AB  - According to the model of "response to injury," the arterial endothelium is
      occasionally injured in hyperlipidemia, hypertension, diabetes mellitus and in
      other states known as risk factors. The ensuing inflammatory response is
      modulated by cytokines and growth factors, among them platelet-derived growth
      factor (PDGF), and monocyte chemoattractant protein-1 (MCP-1). In two independent
      studies, we demonstrated that mRNA levels for PDGF-A and -B and for MCP-1 are
      reduced after ingestion of n-3 fatty acids by human volunteers. This reduction
      persists after monocyte stimulation/differentiation by adherence. Moreover, the
      reduction is brought about only by dietary n-3 fatty acids and not by other
      classes of unsaturated fatty acids (n-6 or n-9). This appears to be one major
      mechanism of action of reduced progression/increased regression of established
      coronary artery disease by ingestion of 1.5 g/d n-3 fatty acids, as assessed by
      coronary angiography in a randomized placebo-controlled double-blind intervention
      study in 223 patients. The study was conducted according to "Good Clinical
      Practice," comprehensive rules regulating investigations with pharmaceutical
      compounds. Together, our investigations lend support to the importance of PDGF-A,
      PDGF-B, and MCP-1 in the pathogenesis of atherosclerosis, and the beneficial role
      of n-3 fatty acids therein.

PMID- 11837998
TI  - n-3 fatty acids and human health: defining strategies for public policy.
AB  - The last quarter of the 20th century was characterized by an increase in the
      consumer's interest in the nutritional aspects of health. As a result,
      governments began to develop dietary guidelines in addition to the traditional
      recommended dietary allowances, which have been superseded now by dietary
      reference intakes. In addition to governments, various scientific societies and
      nongovernmental organizations have issued their dietary advice to combat chronic
      diseases and obesity. Human beings evolved on a diet that was balanced in n-6 and
      n-3 essential fatty acid intake, whereas Western diets have a ratio of n-6/n-3 of
      16.74. The scientific evidence is strong for decreasing the n-6 and increasing
      the n-3 intake to improve health throughout the life cycle. This paper discusses
      the reasons for this change and recommends the establishment of a Nutrition and
      Food Policy, instead of a Food and Nutrition Policy, because the latter
      subordinates the nutritional aspects to the food policy aspects. Nutrition and
      food planning comprise a tool of nutrition and food policy, whose objectives are
      the achievement of the adequate nutrition of the population as defined by
      nutritional science. The scientific basis for the development of a public policy
      to develop dietary recommendations for essential fatty acids, including a
      balanced n-6/n-3 ratio is robust. What is needed is a scientific consensus,
      education of professionals and the public, the establishment of an agency on
      nutrition and food policy at the national level, and willingness of governments
      to institute changes. Education of the public is essential to demand changes in
      the food supply.

PMID- 11838002
TI  - Reforming the GDC.

PMID- 11838003
TI  - Gothic arch tracing.

PMID- 11838004
TI  - Orthodontic specialist lists.

PMID- 11838005
TI  - Orthodontic specialist lists.

PMID- 11838007
TI  - Removable appliances.

PMID- 11838006
TI  - Orthodontic specialist lists.

PMID- 11838008
TI  - Orofacial pain.

PMID- 11838009
TI  - Uncemented crowns.

PMID- 11838010
TI  - Medical book prize awards.

PMID- 11838011
TI  - The accreditation process of an Australian health fund's dental centre.
AB  - Accreditation by a recognised national quality control organisation is the
      ultimate accolade for any service provider. This paper describes the processes
      and procedures that were undertaken by an Australian Health Fund's dental centres
      for accreditation by the Australian Council on Healthcare Standards.

PMID- 11838012
TI  - Spontaneous regression of bilateral dentigerous cysts associated with impacted
      mandibular third molars.
AB  - A case is described where a routine panoramic radiograph revealed radiolucencies,
      compatible with dentigerous cysts, associated with the crowns of bilateral
      impacted lower third molars. Both cysts had regressed in a follow up radiograph
      three years later with no intervention. This is the first reported case of
      spontaneous regression of bilateral dentigerous cysts.

PMID- 11838013
TI  - Medline search validity for randomised controlled trials in different areas of
      dental research.
AB  - OBJECTIVE: To determine the validity of Medline searches for randomised
      controlled trials in dental research (RCT-Ds), using the medical subject headings
      (MeSH-terms). DESIGN: The Medline database was searched for randomised controlled
      trials in dental research (RCT-Ds) published in 1999 and with MeSH-terms
      corresponding to different areas of dental research. All RCT-Ds were manually
      examined for relevance to the different areas of dental research and cross
      tabulated against the Medline search results. The sensitivity, specificity,
      positive (precision) and negative predictive values, as well as the accuracy of
      the search results were calculated. RESULTS: The highest validity in the Medline
      searches for RCT-Ds was seen for endodontics, followed by orthodontics, whereas
      the lowest validity was seen for pediatric dentistry and public health dentistry.
      For pediatric dentistry the MeSH-term searches had too low a sensitivity for
      adequate location of RCT-Ds. CONCLUSIONS: MeSH-term searches on Medline are a
      useful tool for rapid location of RCT-Ds in most areas of dental research.
      However, there is a vast variation in the search validity. More refined search
      strategies are required to locate RCT-Ds in areas of dental research with low
      search validity.

PMID- 11838014
TI  - Surface-assisted reduction of aniline oligomers, N-phenyl-1,4-phenylenediimine
      and thionin in atmospheric pressure chemical ionization and atmospheric pressure
      photoionization.
AB  - Reduction of the oligomers formed from on-line electropolymerization of aniline,
      the compound N-phenyl-1,4-phenylenediimine, and the thiazine dye thionin was
      observed in both an atmospheric pressure chemical ionization and an atmospheric
      pressure photoionization source. The reduction, which alters the mass of these
      analytes by 2 Da, was shown to occur by means of a surface-assisted process which
      involves reactive species, possibly hydrogen radicals, generated from protic
      solvents in the ionization plasma. Reduction was minimized by limiting protic
      solvents, by using a high heated nebulizer temperature, and by using a clean,
      heated nebulizer probe liner. The expected generality of this reduction process,
      and the possibility of similar reduction processes in other plasma ionization
      sources are discussed in relation to the use of these ion sources for on-line
      electrochemistry/mass spectrometry experiments.

PMID- 11838015
TI  - Flow-injection electrospray ionization mass spectrometry of crude cell extracts
      for high-throughput bacterial identification.
AB  - Flow-injection electrospray ionization mass spectrometry (FI-ESI-MS) of
      unfractionated cell-free extracts obtained from bacterial cells suspended in a
      solvent mixture was investigated as a rapid analytical method for reproducible,
      high-throughput bacterial identification. Five bacterial strains (two Escherichia
      coli, two Bacillus spp. and one Brevibacillus laterosporus) were studied in this
      investigation. Axenically grown bacterial cells were suspended in an acidic
      organic solvent and the cell-free extract was sequentially injected into a
      solvent flow stream that was sprayed into the ionization chamber of the ESI-MS.
      The spectra produced contained reproducible information, which was useful for
      discriminating between the bacteria. Tandem mass spectrometry was used to
      characterize further the peaks, and at least three classes of macromolecules,
      namely phospholipids, glycolipids, and proteins, were found to contribute most to
      the spectral information. Bacterial extracts stored under different conditions
      gave very similar mass spectra for each of the five bacterial strains, indicating
      that the extracts were stable even at room temperature for up to 24 h, with no
      loss of information content, which has obvious implications for automated high
      throughput analysis. An analysis of the components of the extracting solvent
      mixture and their effects on the spectral information showed that acetonitrile
      contributes most significantly to the extraction process and hence to the
      information content of the spectra.

PMID- 11838016
TI  - On the nature of the chemical noise in MALDI mass spectra.
AB  - The so-called "chemical noise background" imposes a major limit on the practical
      sensitivity of MALDI mass spectrometry. Typically, as the amount of material of
      interest subjected to MALDI analysis is reduced, the signal decreases to the
      point where it can no longer be differentiated from the chemical noise. Using a
      newly designed MALDI-ion trap mass spectrometer, we describe experiments intended
      to throw light on the nature of the chemical noise background and to reduce its
      effects. Single-stage mass spectrometric signals from peptides were observed to
      disappear into the noise when the amount of sample applied to the MALDI sample
      stage was decreased to less than a femtomole. At these low levels, analysis of
      the collision-induced fragmentation spectra revealed the presence of ions
      originating from the peptide as well as cluster ions that originate from the
      chemical noise. The fragmentation pattern arising from dissociation of the
      cluster species suggests that they are composed largely of matrix molecules. A
      significant fraction of these cluster ions can be dissociated at activation
      energies lower than the threshold for peptide fragmentation. We used this finding
      to collisionally pre-activate MALDI ions to remove a significant portion of the
      chemical noise from the spectrum, allowing us to obtain readily discernible
      single stage MS signals from 100 attomols of peptide. The strategy also yielded
      high quality MS/MS spectra from 100 attomols of peptide. Different possibilities
      of collisional pre-activation for improving sensitivity are considered.

PMID- 11838017
TI  - Mass correlated acceleration in a reflectron MALDI TOF mass spectrometer: an
      approach for enhanced resolution over a broad mass range.
AB  - Compared to continuous extraction, pulsed extraction (PE) of ions formed by
      matrix-assisted laser desorption/ionization (MALDI) in time-of-flight (TOF) mass
      spectrometers significantly improves mass resolution. Parameters such as
      extraction voltage, delay time, and correction pulse must be varied, however, to
      achieve optimum mass resolution over a broad mass range because the PE method is
      mass dependent. We previously reported a novel method, mass correlated
      acceleration (MCA), which we have now combined with a reflectron MALDI TOF mass
      spectrometer to further enhance mass resolution over a broader mass range. Unlike
      the PE method, MCA is not mass dependent and high resolution mass spectra can be
      achieved with a single tuning of instrument parameters. The ions may be brought
      into focus simultaneously, i.e., the multi-channel recording advantage can be
      more fully realized. The MCA dual-stage ion source design includes an extraction
      pulse region and an acceleration region that contains a time-dependent waveform
      correlated with mass. We demonstrate the validity of this novel technique with
      applications in peptide mixture analysis and protein digests of lysozyme and
      bovine serum albumin.

PMID- 11838018
TI  - ESI-FTICR mass spectrometry employing data-dependent external ion selection and
      accumulation.
AB  - Data-dependent external m/z selection and accumulation of ions is demonstrated in
      use with ESI-FTICR instrumentation, with two different methods for ion selection
      being explored. One method uses RF/DC quadrupole filtering and is described in
      use with an 11.5 tesla (T) FTICR instrument, while the second method employs RF
      only resonance dipolar excitation selection and is described in use with a 3.5 T
      FTICR instrument. In both methods ions are data-dependently selected on the fly
      in a linear quadrupole ion guide, then accumulated in a second linear RF-only
      quadrupole trap that immediately follows. A major benefit of ion preselection
      prior to external accumulation is the enhancement of ion populations for low
      level species. This development is expected to expand the dynamic range and
      sensitivity of FTICR for applications including analysis of complex polypeptide
      mixtures (e.g., proteomics).

PMID- 11838020
TI  - Detailed analysis of alpha,omega-bis(4-hydroxybutyl) poly(dimethylsiloxane) using
      GPC-MALDI TOF mass spectrometry.
AB  - In this study the prepolymer alpha,omega-bis(4-hydroxybutyl)
      poly(dimethylsiloxane), used in the formulation of oxygen permeable films, is
      evaluated by gel permeation chromatography (GPC) combined with matrix assisted
      laser desorption ionization (MALDI) time of flight (TOF) mass spectrometry (MS).
      Two unexpected mass distributions are observed in the mass spectra. Reaction
      schemes for the formation of these distributions are proposed. A solution phase
      trimethylsilane end group modification was performed on the prepolymer to
      determine whether the unexpected mass distributions occur as impurities from
      synthesis or as artifacts from the MS process. Evaluation of the TMS modified
      prepolymer indicates the unexpected mass distributions indeed occur as impurities
      from the synthetic procedure. Average molecular weight values are determined by
      traditional GPC, direct MALDI-TOF MS, and GPC-MALDI-TOF MS methods and the
      results are compared.

PMID- 11838019
TI  - A study of peptide-peptide interactions using MALDI ion mobility o-TOF and ESI
      mass spectrometry.
AB  - Matrix-assisted laser desorption ionization ion mobility coupled to orthogonal
      time-of-flight mass spectrometry (MALDI-IM-oTOF MS) is evaluated as a tool for
      studying non-covalent complex (NCX) formation between peptides. The NCX formed
      between dynorphin 1-7 and Mini Gastrin I is used as a model system for comparison
      to previous MALDI experiments (Woods, A. S.; Huestis, M. A. J. Am. Soc. Mass
      Spectrom. 2001, 12, 88-96). The dynorphin 1-7/Mini Gastrin I complex is stable
      after more than a ms drift time through the He filled mobility cell. Furthermore,
      the effects of solution pH on NCX ion signal intensity is measured both by MALDI
      IM-MS analysis and by nanoelectrospray mass spectrometry. When compared to the
      previous MALDI study this work shows that all three techniques give similar
      results. In addition, fragmentation can be observed from of the non-covalent
      complex parent ion that occurs prior to TOF mass analysis but after mobility
      separation, thus providing NCX composition information.

PMID- 11838021
TI  - Poly(ethylene glycol) doubly and singly cationized by different alkali metal
      ions: relative cation affinities and cation-dependent resolution in a quadrupole
      ion trap mass spectrometer.
AB  - Structural information of gas phase complexes of poly(ethylene glycol) (PEG)
      cationized by one or two different alkali metal ions is inferred from MS and
      MS/MS experiments performed with an electrospray quadrupole ion trap mass
      spectrometer. The rationale for selecting PEG was that its sites for cation
      binding are non-selective with respect to the repeating monomeric unit of the
      polymer, but there is selectivity with respect to the formation of an inner
      coordination sphere specific to each metal ion. The dissociation of [M1+ M2+
      (EO23)], where EO23 = linear polymer of ethylene oxide, 23 units in length,
      resulted in loss of one of the alkali metal ions, with preference for loss of the
      larger cation, with no fragmentation of the PEG backbone for Na, K, Rb, and Cs.
      Li was not examined in this portion of the study. The selectivity for loss of the
      larger alkali metal ion was [Na+ K+ (EO23)] to [Na+ (EO23)] + K+ at 100%; [K+ Rb+
      (EO23)] to [K+ (EO23)] + Rb+ at 93%; and [Rb+ Cs+ (EO23)] to [Rb+ (Eo23)] + Cs+
      at 99%. The resolution of [M+ (EOx)] for x = 20-30 was dependent on the alkali
      metal ion, with the highest resolution observed for Cs+ and the lowest for Na+.
      These results are discussed with respect to the packing of the oxygen atoms on
      PEG (M.W.(avg) = 1000) around an alkali metal ion of different radius, and how
      this packing leads to an ensemble of unique structures, and therefore mobilities
      for [M+ (EOx)].

PMID- 11838022
TI  - Characterization of the elusive disulfide bridge forming human Hb variant: Hb Ta
      Li beta83 (EF7)Gly --> Cys by electrospray mass spectrometry.
AB  - An electrospray mass spectrometric approach to the identification of a human
      hemoglobin (Hb) variant involving a Cys residue incorporation is presented. In Hb
      Ta-Li (beta83Gly --> Cys), Cys83 forms inter-molecular disulfide bridges. Routine
      analysis of the denatured Hb showed the presence of a minor beta chain variant
      whose mass apparently was 1 Da less than the expected mass difference of 46 Da
      for a Gly --> Cys substitution. Reduction of the globin chains with
      dithiothreitol gave an intense monomer with the expected mass difference for the
      Gly --> Cys substitution. After reprocessing the original raw data from the
      denatured Hb and taking into account the possibility of dimer formation, a
      component was revealed whose mass was consistent with a disulfide linked dimer of
      Ta-Li beta globins. The mutation was localized to peptide betaT10 by analysis of
      a tryptic digest. Tandem mass spectrometry and DNA sequencing confirmed the Gly -
      > Cys substitution occurred at residue 83 of the beta chain. Problems encountered
      in identifying the components in mixtures of monomers and dimers are discussed.

PMID- 11838023
TI  - Gas-phase reactions of charged phenyl radicals with neutral biomolecules
      evaporated by laser-induced acoustic desorption.
AB  - A generally applicable method for the study of phenyl radicals' reactions with
      neutral biomolecules in the gas phase is demonstrated. Neutral biomolecules were
      evaporated into a Fourier-transform ion cyclotron resonance mass spectrometer (FT
      ICR) by means of laser-induced acoustic desorption (LIAD) and subsequently
      reacted with trapped charged phenyl radicals. The structural integrity of the
      evaporated alanylalanine molecules was verified by reaction with
      dichlorophosphenium ions. Examination of the reactions of charged phenyl radicals
      with alanylalanine and thymidine evaporated via LIAD revealed hydrogen atom
      abstraction for both alanylalanine and thymidine as well as an
      addition/elimination product for the reaction with thymidine. These reactions are
      consistent with the results obtained by others in solution. Further, a previously
      unstudied reaction of the nucleotide of thymine (T1) with charged phenyl radical
      was found to yield analogous products as the reaction with thymidine.

PMID- 11838024
TI  - Dissociative phenomenology of dissociative identity disorder.
AB  - The goal of this study was to investigate the dissociative phenomenology of
      dissociative identity disorder (DID). The Multidimensional Inventory of
      Dissociation (MID) was administered to 34 patients with DID, 23 patients with
      dissociative disorder not otherwise specified (DDNOS), 52 patients with mixed
      psychiatric disorders, and 58 normal individuals. DID patients obtained
      significantly higher scores than the other three groups on 27 dissociation
      related variables. DDNOS patients had significantly higher scores than normals
      and mixed psychiatric patients on 17 and 15 dissociation-related variables,
      respectively. The findings of the present study are virtually identical to a
      large body of replicated findings about the dissociative phenomenology of DID.
      This broad range of dissociation-related phenomena, which routinely occurs in
      individuals with DID, is largely absent from the DSM-IV-TR account of DID. Factor
      analysis of the 11 dimensions of dissociation that are measured by the MID
      extracted only one factor that accounted for 85% of the variance. It was
      concluded that dissociation is a unifactorial taxon or natural type that has
      different aspects or epiphenomena (i.e., amnesia, depersonalization, voices,
      trance, etc.).

PMID- 11838025
TI  - Identifying safety behaviors in insomnia.
AB  - The aim of the present study was to systematically elicit the safety behaviors
      employed by people with insomnia. Safety behaviors have been identified as
      contributing to the maintenance of anxiety disorders. They include overt or
      covert strategies designed to prevent a feared outcome. However, they contribute
      to the maintenance of the disorder because they prevent unambiguous
      disconfirmation of unrealistic beliefs and they increase the likelihood that the
      fear would actually occur. A questionnaire based on the Dysfunctional Beliefs and
      Attitudes about Sleep Scale was developed to elicit safety behaviors and was
      administered to 33 people meeting criteria for primary insomnia and 33 nonpatient
      controls. The data indicated that people with insomnia use a wide range of safety
      behaviors to prevent feared outcomes. Blind raters determined that the safety
      behaviors reported included those that: interfere with the regularity of the
      sleep cycle, interfere with sleep directly, cause paradoxical fuelling of
      presleep cognitive activity, exacerbate day-time sleepiness, contribute to the
      day being unpleasant or boring, and those that increase preoccupation with sleep.
      The clinical implications of these findings and areas for further research are
      discussed.

PMID- 11838026
TI  - Psychological defenses of Danish medical students.
AB  - Patterns in the psychological defenses of medical students may have implications
      for the way they handle and respond to the pressures and developmental issues
      they encounter in medical school and beyond. Using the Defense Style
      Questionnaire (DSQ40) to assess psychological defenses, a sample of first-year
      Danish medical students was compared with a sample of students at a short-term
      boarding school for general education. The medical students scored significantly
      higher on items connected with pseudo-altruism, denial, and undoing. Trends in
      the data furthermore suggest a greater use of sublimation, rationalization, and
      dissociation among medical students. When defense mechanisms were labeled into
      mature, neurotic, and immature categories, there were no differences between the
      groups or in the total defense scores.

PMID- 11838027
TI  - Need for closure and jumping-to-conclusions in delusion-prone individuals.
AB  - Members of the general population were screened for delusion-proneness using the
      Peters et al. Delusions Inventory (PDI). Two groups were formed from the
      participants who scored in the upper and lower quartiles of the PDI and compared
      on a probability judgment task and on the Need for Closure scale (NFC). The study
      investigated whether the "jump-to-conclusions" (JTC) reasoning bias,
      characteristic of deluded participants, could be found in delusion-prone
      individuals. NFC was investigated as a motivational factor that may correlate
      with this reasoning bias. Evidence for the existence of the data-gathering, but
      not the probability judgment, part of the JTC reasoning bias was found in the
      delusion-prone individuals. This group also scored significantly higher on the
      NFC scale. As the data-gathering reasoning bias was found in delusion-prone
      individuals this suggests that it may be involved in the formation, rather than
      merely the maintenance, of delusional beliefs.

PMID- 11838028
TI  - Assessment and treatment of depression in disability claimants: a cost-benefit
      simulation study.
AB  - The economic burden of depression includes direct costs of treatment, as well as
      absenteeism and reduced productivity. In this study, we consider the costs and
      benefits of an intervention to assess and treat depressive symptoms in long-term
      disability claimants with nonpsychiatric medical illnesses. Cost-benefit
      simulations were conducted using data from a study sample of long-term disability
      claimants (N = 1229) and estimates of both the costs of treatment of depressive
      symptoms and the savings in claims payments for those who return to work as a
      result of treatment. We show that the savings that stem from returning a very few
      claimants to work can offset the assumed cost of a comprehensive program for the
      assessment of depressive symptoms in all claimants and intensive treatment of
      those with depressive symptoms. The economic and public health benefits both
      point toward the value of such an intervention for disability claimants.

PMID- 11838029
TI  - Cultural, psychological, and demographic correlates of willingness to use
      psychological services among East Asian immigrants.
AB  - To assess East Asian immigrants' willingness to use psychological services if
      depressed and willingness to recommend psychological services to distressed
      friends, and to examine their cultural (acculturation status, self-construal,
      ethnic identity), psychological, and demographic correlates, 170 East Asian
      immigrants (88 male, 82 female) were administered a battery of psychometrically
      established measures. Approximately 50% of participants expressed strong
      unwillingness to seek psychological treatments, and approximately 30% expressed
      strong unwillingness to recommend such treatments to distressed friends. Personal
      willingness to use psychological services was positively associated with
      assimilation, being female, age, and English fluency, but was negatively
      associated with interpersonal distance and number of years in the United States.
      In contrast, willingness to recommend psychological services to friends was
      positively associated with independent self-construal, overall ethnic identity,
      interpersonal sensitivity, being female, and number of years in the United States
      but was negatively associated with interpersonal distance and reported obsessive
      compulsive symptoms. A minority of East Asian immigrants report being willing to
      seek or to recommend psychological services. Psychological distress, and cultural
      and demographic features were differentially associated with willingness to seek
      versus willingness to recommend psychological services.

PMID- 11838030
TI  - Pathology of drunkenness--is it a disease or a moral delinquency? 1875.

PMID- 11838031
TI  - Retraumatization of Israeli civilians during a reactivation of the Gulf War
      threat.

PMID- 11838032
TI  - The relationship of olfactory delusional disorder to social phobia.

PMID- 11838033
TI  - Effect of brief versus long-term inpatient treatment on homecoming stress in
      combat-related posttraumatic stress disorder: three-year follow-up.

PMID- 11838034
TI  - Mental disorders and quality of care among postacute myocardial infarction
      outpatients.

PMID- 11838036
TI  - Survey of instruments. Coagulation analyzers.

PMID- 11838035
TI  - Long-term assessment of personality after burn trauma in adults.

PMID- 11838037
TI  - [Finite element assisted study of the mechanical stability of 2 selected
      osteosynthesis systems for mandibular osteotomy].
AB  - The aim of this study was to use the finite element method (FEM) to compare the
      stability of 2.0 mm titanium screws in a triangular configuration with that of a
      2.0 mm titanium miniplate as osteosynthesis material following bilateral sagittal
      split osteotomy. To this end, a model of the mandible was produced, consisting of
      19,854 elements and 4285 nodes. The mechanical parameters of the materials
      investigated were taken from the literature or notified by the manufacturer. On
      condition that the materials were subjected only to their respective ultimate
      tensile stress, it was possible to neutralise the following masticatory force:
      124.6 N with the miniplate and 167.5 N with the bicortical triangular screw
      configuration. The limitation of stress ensued from the peri-implant bone and not
      from the osteosynthesis material per se. The finite element method (FEM) appears
      to be suitable for simulating complex mechanical stress situations in the
      maxillofacial area, as also demonstrated by the fact that our data agree with
      those in the literature and with clinical experience. It will enable considerable
      savings to be made in terms of time and materials (animal experiments) in the
      future development of osteosynthesis materials and techniques.

PMID- 11838038
TI  - [Long-term outcome of dentoalveolar trauma in relation to post-traumatic
      instability].
AB  - PURPOSE: The aim of this retrospective study was to investigate the long-term
      outcomes of dental injuries. Subluxated and laterally luxated teeth were
      evaluated according to the findings of CO2 sensitivity, obliteration, pulpal
      sclerosis, and the duration of post-traumatic fixation of the injured teeth.
      MATERIAL AND METHODS: The data of 725 patients were analyzed retrospectively over
      a period of 14 years. Of these, 108 patients could be investigated for a long
      term follow-up. Dental trauma was classified according to the degree of luxation
      (I-III). RESULTS: There was a significant correlation between the degree of
      luxation and the post-traumatic findings of CO2 sensitivity. There was no
      significant correlation between the degree of luxation and the post-traumatic
      findings of apical inflammation, pulpal sclerosis, and/or obliteration. Long-term
      fixation of injured teeth had no effect on the short- and long-term occurrence of
      pathologic processes at the root such as root resorption. CONCLUSION: The post
      traumatic finding of CO2 sensitivity was related to the degree of luxation of the
      injured teeth. Apical inflammation, pulpal sclerosis, and obliteration were not
      related to the degree of luxation. The results suggest that long-term fixation of
      injured teeth has no negative effects on the long-term outcomes of subluxated and
      laterally luxated teeth.

PMID- 11838039
TI  - [Optimized hemodilution with hydroxyethyl starch. A blood saving method in
      malocclusion operations].
AB  - OPTIMIZED HEMODILUTION: To avoid blood transfusions, the method of optimized
      hemodilution (OHD) was developed. OHD consists of preoperative hypervolemic
      hemodilution with 500 ml hydroxyethyl starch (HES) and consecutive volume
      replacement with HES in the case of intraoperative intravasal fluid loss. This
      study verifies the efficacy of OHD. RESULTS: Mono- and bimaxillary operations (n
      = 213) performed between January 1995 and May 1999 were evaluated retrospectively
      with respect to reduction of blood transfusions due to application of OHD. The
      average blood loss in the OHD group (n = 127) was 593 ml, and no blood
      transfusion was required. In contrast, the control group (n = 86) showed an
      average blood loss of 738 ml, and 15% of these patients (n = 13) required
      transfusion of a total of 18 blood units. Based on our results, provision of
      autologous blood is only necessary for patients who do not receive OHD. The costs
      of fluid replacement and transfusion are increased by a factor of 5.7 when OHD is
      not used. DISCUSSION: OHD should be preferably used in cases of elective surgery
      on patients with good cardiopulmonary health. It is an easy to handle infusion
      regimen, which does not require additional monitoring, has no risk of infection,
      and results in a significant cost reduction.

PMID- 11838040
TI  - [Complications in surgical treatment of malocclusions. Report of 50 years
      experience].
AB  - BACKGROUND: During the past few decades, orthognathic surgery has become routine
      in oral and maxillofacial surgery. As these surgical interventions are elective,
      the goal is a low complication rate. The aim of this study was to analyze the
      intraoperative and postoperative complications after orthognathic surgery without
      considering orthodontic relapse. PATIENTS AND METHODS: The medical files of 507
      patients were reviewed who had been treated in the department of oral
      maxillofacial surgery at the Martin-Luther-Universitat in Halle-Wittenberg during
      a period of 51 years. The indication for orthognathic surgery was mandibular
      hyperplasia in 314 cases (61.9%), mandibular hypoplasia in 69 cases (13.6%),
      mandibular hyperplasia with a frontal open bite in 53 cases (10.5%), maxillary
      hyperplasia with a cleft in 30 cases (5.9%), maxillary hyperplasia in 22 cases
      (4.3%), severe laterognathia in 10 cases (2.1%), and isolated frontal open bite
      in 9 cases (1.5%). The surgical procedures were as follows: bilateral sagittal
      split osteotomy (n = 336, 66%), Le Fort I osteotomy (n = 29, 5.9%), bimaxillary
      osteotomy (n = 35, 6.3%), and segment osteotomy (n = 107, 21.1%). Rigid fixation
      was used in 147 patients. RESULTS: In 55% of the patients a postoperative
      neurosensory deficit of the inferior alveolar nerve was observed, which was only
      found in 28% after 1 year. Inflammatory wound healing was found in 5.3% of the
      patients. CONCLUSION: Due to antibiotic perioperative prophylaxis and modern
      rigid osteosynthesis devices, orthognathic surgery has become a routine method in
      maxillofacial surgery with predictable surgical results.

PMID- 11838041
TI  - [Wavy incision of the soft palate. Modification of intravelar veloplasty].
AB  - PURPOSE: The problem with primary soft palate repair is shortness of the soft
      palate and a soft tissue deficit in this region. The authors introduce a
      modification of the intravelar veloplasty allowing lengthening of the soft palate
      at the time of primary closure. METHODS: The "soft palate wavy incision
      procedure" combines a wavy or undulating type of incision at the velar cleft
      margins with intravelar veloplasty. In 12 patients with complete clefts of the
      palate, postoperative breathing and speech was analyzed 3 years later. The
      investigator did not know whether a modification of the common procedure had been
      performed in these patients or not. RESULTS: It was found that the soft palate
      wavy line procedure is easy to perform and closure in three layers is possible
      even in wide clefts of the soft palate. No postoperative fistula was observed. An
      average lengthening of the soft palate of about 56% (24-83%) was achieved,
      measured immediately at the end of surgery. Three years later the patients have
      good speech results following this technique. CONCLUSIONS: Experience has shown
      that the soft palate wavy incision procedure is straightforward, safe, and easy.
      It seems that this technique leads to better results than classic intravelar
      veloplasty. This paper is only a first report, and further investigations are
      necessary.

PMID- 11838042
TI  - [Interdisciplinary treatment of a 3 1/2-year-old child with extensive
      ameloblastic fibro-odontoma. Case report and follow-up documentation over 21 1/2
      years].
AB  - BACKGROUND: This report deals with a 3 1/2 year old patient with an ameloblastic
      fibro-odontoma of the frontal part and left corpus of the mandible. The tumor had
      become symptomatic 2 months prior to admittance by a local, painless swelling of
      the bone and the mobility of teeth. The initial findings and the progress of the
      disease led to the preliminary diagnosis of a malignant mesenchymal tumor. Its
      extent and aggressive growth prompted a continuity resection of the mandible and
      immediate reconstruction with a costal autograft. The definitive histological
      diagnosis was an ameloblastic fibro-odontoma. The patient was followed up over a
      period of 21 1/2 years. THERAPY: Further treatment included an iliac crest onlay
      graft, followed by autotransplantation of three third molars into both
      transplants. Two of the wisdom teeth had to be replaced by dental implants
      because of ankylosis and infra-occlusal positioning. The prosthetic
      rehabilitation was carried out by a bar attachment and a partial cover denture.
      This report supports the concept of the interdisciplinary treatment of patients
      with tumors that occur during the growth phase.

PMID- 11838043
TI  - Tuberculosis and HIV.

PMID- 11838044
TI  - [Classification of a 300,000-year-old dental crown of the upper loamy deposit of
      the Bad Canstatter travertine zone].
AB  - Hominid dental remains were recovered in association with fossil bones and
      artifacts during systematic excavations in a loamy deposit located between the
      two travertine zones T4 and T5 at Stuttgart-Bad Cannstatt, Southwest Germany.
      Direct dating of a hominid tooth crown with thermoluminescence resulted in a date
      of 300 kya, which is in agreement with the Holstein Interglacial floral and
      faunal composition of this layer. The specimen is a lower left canine with
      hypoplastic morphology. This interpretation is supported by thorough assessment
      of its overall morphology, comparative metric evaluation, and by scanning
      electron microscopy analyses of the enamel prisms. Additional microstructural
      comparison of these dental remains with a tooth from the same site, but derived
      from a Cervidae specimen supported the distinct differences between both teeth.
      Here we discuss both the classification and significance of the specimen's
      evolutionary position as well as compare this specimen with stomatologic results
      from previous palaeopathological research.

PMID- 11838046
TI  - On the validity of individual age-at-death diagnosis by incremental line counts
      in human dental cementum. Technical considerations.
AB  - Histological analysis of 91 roots from 80 freshly extracted teeth from patients
      with known calendar age and life-history parameters revealed that the validity of
      a chronological age-at-death diagnosis based on the count of incremental lines in
      human dental cementum is essentially dependent from two parameters: method of
      analysis, and pathological state of the investigated tooth. In this paper, we
      want to contribute to the establishment of a methodological standard procedure by
      comparison of our own results with otherwise published research designs. We
      conclude that as long as the necessary prerequisites are met, the quantitative
      analysis of cementum annulli will lead to a rather precise chronological age-at
      death diagnosis. In addition, a qualitative analysis permits the ontogenetic
      dating of certain individual life-history parameters (e.g. previous pregnancies).

PMID- 11838045
TI  - [Epigenetic markers in migrating population burial sites of the Mid-Elbe-Saale
      area].
AB  - The distribution of 122 epigenetic traits of the cranium and the postcranial
      skeleton (180 skeletal individuals) of six sites of the period of the Middleelbe
      Saale-Region was analyzed. Based on these frequencies and using the method of
      biodistance analysis (MMD after Sjovold 1973) the relationships of these
      population groups were investigated which are different concerning their
      geographical origin. The results did not show distinct differences between these
      groups, but suggested a possible homogeneity of our populations.

PMID- 11838048
TI  - Dermatoglyphic analysis of Habans (Hutterites) from Slovakia.
AB  - Dermatoglyphic traits have been used to assess population structure and
      affinities of the 91 Habans (Hutterites) and 162 Non-Haban Slovaks. In addition a
      comparison has been made with other Slovak population samples. Biological
      distances between individual populations were assessed by means of the Hiernaux
      distance coefficient. The results show a clear separation of the Habans from the
      Non-Habans in the same villages as well as from the other Slovak groups.
      Dermatoglyphic analysis is regarded as noncompatible with the interpretation of
      the genetic structure.

PMID- 11838047
TI  - Bone mineral density is associated with estrogen receptor gene polymorphism in
      men.
AB  - In order to identify genetic effects of allelic variation on bone mineral density
      (BMD), association studies have been performed recently. Examining the relation
      between PvuII and XbaI restriction fragment length polymorphism (RFLPs) at the
      estrogen receptor (ER alpha) gene and BMD, in women or men, have yielded
      conflicting results. We analyzed the association between this polymorphism and
      BMD Z score values of cancellous bone at the 3rd finger in 344 members of nuclear
      families of European population, Chuvasha, living in Russia. The population
      sample included 183 males, aged 18-84, and 161 females, aged 23-79. The analysis
      has been performed separately for both sexes and for both generations (parents
      and offspring). We used a novel direct haplotyping method, which determines
      simultaneously each of the PvuII and XbaI RFLPs and their relation to each other.
      The haplotypes were represented as the combination of both polymorphic sites on
      the same chromosome, by using P/p and X/x for PvuII and XbaI restriction sites,
      respectively. The subjects were classified into 3 groups of genotypes: A = PXPX
      (homozygote for the PX haplotype); B = PXPx, PXpx (the heterozygotes for the PX
      haplotype); C = PxPx, Pxpx, pxpx (genotypes that are lacking the PX haplotype).
      The PXPX genotype (A) was associated with higher BMD Z score values in comparison
      to the genotypes that are lacking the PX haplotype (C), in total males [0.618 vs.
      -0.133 (p = 0.004)] and for the "sons" generation [0.724 vs. -0.198 (p = 0.02)].
      Similar tendency was observed for the "fathers" generation (0.539 vs. -0.085),
      though the difference did not approach statistical significance (p = 0.087).
      These findings were not found in the female samples, nor in the "mothers" or
      "daughters" generations. The question if there are differences in the mode of
      action of estrogen through its receptor on bone mass, between the genders or
      between the males' generations, have to be further investigated.

PMID- 11838049
TI  - A morphometric study of the Thingbu-pa and population comparison with
      neighbouring Monpa tribes of Arunachal Pradesh, India.
AB  - In the present study an attempt has been made to examine the morphometric
      characteristics of the adult males of the Thinbu-pa and the nature and extent of
      morphometric variation among four neighbouring Monpa groups of Arunachal Pradesh
      (India), namely the Panchen-pa, Dirang Monpa, Tawang Monpa and Kalaktang Monpa.
      For the sake of investigation altogether 14 anthropometric measurements (11
      pertaining to head and face and 3 on the body as a whole) have been taken and 5
      indices have been calculated. To obtain the distance values the methods of
      Penrose (1947, 1954) and El-Najjar (1978) have been followed. It is observed that
      the Thingbu-pa maintain far distance with the four neighbouring Monpa groups as
      well as the Panchen-pa also maintain far distance with the other four groups,
      while the Dirang Monpa, Tawang Monpa and Kalaktang Monpa maintain close distance
      among each other.

PMID- 11838050
TI  - [An experimental study of antisense TGF-beta 1 inhibiting keloid fibroblast
      proliferation in vitro].
AB  - OBJECTIVE: To study the effect of antisense TGF-beta 1 on keloid fibroblast
      proliferation in vitro. METHODS: The antisense TGF-beta 1 was transfected into
      the keloid fibroblast by liposome. The cell count technique was used to test the
      effect of antisense TGF-beta 1 on keloid fibroblast proliferation in vitro. Cell
      apoptosis was tested by FCM. RESULTS: Antisense TGF-beta 1 can inhibit the
      proliferation of keloid fibroblast in vitro; Antisense TGF-beta 1 can increase
      the apoptosis ratio of keloid fibroblast in vitro. CONCLUSIONS: Antisense TGF
      beta 1 can induce keloid fibroblast apoptosis and inhibit keloid fibroblast
      proliferation in vitro, which may contribute to the inhibition of keloid
      formation in vivo.

PMID- 11838051
TI  - [The biological effect of verapamil on hypertrophic scar fibroblast].
AB  - OBJECTIVE: To study the mechanism of calcium channel antagonist Verapamil on the
      treatment of hypertrophic scar and explore the possibility of further clinical
      application. METHODS: After six strains of HSFB were cultured in vitro, we
      investigated HSFB proliferation by MTT method, investigated HSFB collagen
      synthesis by 3H-proline uptaken and Hydroxyproline colorimetric analysis, and
      investigated collagen gene expression by Northern Blot. RESULTS: Verapamil can
      inhibit HSFB proliferation, collagen synthesis and gene expression by a dose
      depended manner, especially treated with 100 mumol/L Verapamil. CONCLUSION: By
      inhibiting I, III procollagen gene expression, Verapamil can inhibit the
      formation of hypertrophic scar.

PMID- 11838052
TI  - [Response of keloid fibroblasts to the effect of tumor necrosis factor-alpha(TNF
      alpha)].
AB  - OBJECTIVE: To investigate the biologic behavior of keloid fibroblasts and the
      pathogenesis of keloid. METHODS: Human dermal fibroblasts cultured from normal
      skin and keloid were treated with tumor necrosis factor-alpha(TNF-alpha) for 48
      hours at 10(3) U/ml and 10(4) U/ml. Collagen production by fibroblasts was
      assessed by 3H-proline in corporation into pepsin-resistant, precipitated
      extracellular collagenous protein. RESULTS: TNF-alpha caused a concentration
      dependent reduction in collagen production in normal dermal fibroblasts.
      Treatment with TNF-alpha at 10(3) U/ml significantly reduced the collagen
      synthesis in keloid fibroblasts (P < 0.01). However, the collagen synthesis in
      keloid fibroblasts did not further decreased after exposure to TNF-alpha at 10(4)
      U/ml. CONCLUSIONS: Keloid fibroblasts may remain less sensitive to the inhibitory
      effects of TNF-alpha on collagen synthesis to a certain extent.

PMID- 11838053
TI  - [Experimental study of the effect of Hpudiod cream on random flap survival in
      rats].
AB  - OBJECTIVE: To explore the effect of Hpudiod cream on blood circulation of flap.
      METHODS: 80 rats were casually divided into two groups: the experiment and the
      control group. A random flap was created on the back of the animal. Flap survival
      and necrosis were observed in the two groups. The flaps were examined
      histologically and the capillaries were counted. RESULTS: On the 5th and 7th day
      after operation, the distant ends of the flaps necrosed in both groups. On the
      5th day there was no significant difference between the two groups in the number
      of the capillary in the middle of the flap (P > 0.05). On the 7th day, the
      capillary in the middle of the flap increased in the treatment group(P < 0.05).
      CONCLUSION: Hpudiod cream can improve the blood circulation of the random flap
      evidently.

PMID- 11838054
TI  - [Clinical applications of variform free flaps of the scapular region for cervical
      burn contracture].
AB  - OBJECTIVE: To provide ideal materials for cervical burn contracture repair
      through a morphological study of free flaps of the scapular region. METHODS:
      Variform free flaps of the scapular region were designed according to the
      cervical defect after scar had been resected. The angiosomes of each cutaneous
      branch of the circumflex scapular artery (CSA) were observed and investigated
      through uninterrupted extension of the flap size. RESULTS: A total of 73 cases of
      cervical burn contracture have been treated with free flaps of different shapes
      of the scapular region since 1992. 41 were fusiform flaps pedicled on ascending
      and descending branches of the CSA. 26 were three-lobe flaps pedicled on
      ascending, transverse and descending branches of the CSA. 6 cases were two-lobe
      flaps pedicled on transverse and ascending or branches of the CSA. Two fusiform
      flaps necrosed owing to atherosclerosis and hyperemesis. The survival rate of the
      flaps was 97.26%. CONCLUSIONS: The free flaps of scapular region could be
      designed in different based on the three cutaneous branches of the CSA. More
      diverse designs can be expected since the report of the inflamammary branches of
      the CSA recently.

PMID- 11838055
TI  - [The parascapular free flap extended to the inframammary fold].
AB  - OBJECTIVE: To report the application of the parascapular free flap extending to
      the inframammary fold. METHODS: The longitudinal axis of the free flap lay
      curvilinearly from the inframammary fold to the circumflex scapular artery at the
      trilateral foramen. The largest flap was 32 cm x 11 cm. RESULTS: The flap was
      successfully used in 4 female patients to repair their facial and cervical burn
      scar. All the flaps survived well. CONCLUSIONS: The parascapular free flap
      extending to the inframammary fold enlarged the range of the flap application.
      The donor-site scar of the flap is well hidden within the inframammary fold. Thus
      the unavoidable widening and hypertrophy of the donor-site scar of the
      traditional-designed parascapular or scapular flap were minimized. This flap will
      apply to male patients also.

PMID- 11838056
TI  - [Breast reconstruction with a TRAM flap].
AB  - OBJECTIVE: Breast reconstruction with a transverse rectus abdominis myocutaneous
      (TRAM) flap was performed to enhance the mental and physical well-being of
      patients. METHODS: The experience with TRAM breast reconstruction in 42 patients
      was reviewed. The patient selection, flap design and our operative technique were
      introduced in detail. RESULTS: TRAM breast reconstruction was performed as
      immediate reconstruction in 25 patients, as delayed reconstruction in 17 cases. 2
      cases had partial skin necrosis in the abdominal donor site. 2 had partial
      necrosis of the TRAM flap. One patient had abdominal hernia. CONCLUSIONS: The
      additional vascular anastomosis or double-pedicle TRAM flap with intramuscular
      dissection was the key points to reduce complications. Due to the difficulty of
      TRAM flap reconstruction, thorough understanding of the technique and surgical
      accuracy are necessary for both flap safety and aesthetic pleasing results.

PMID- 11838057
TI  - [Phalloplasty using an abdominal flap with two sources of blood supply (16 cases
      reports)].
AB  - OBJECTIVE: To improve the survival of a reconstructed penis and reduce injury of
      the donor site at the abdominal wall. METHODS: Sixteen cases of phalloplasty were
      performed using an abdominal flap based on two sources of blood supply i.e. the
      cutaneous branches of the inferior epigastric blood vessel and the superficial
      epigastric blood vessel. RESULTS: All of the operations were successful.
      CONCLUSIONS: With abundant blood supply and high survival rate and the advantage
      of easy transposition, the flap is a good option for phalloplasty.

PMID- 11838058
TI  - [Investigation on skin retrograde degeneration after tissue expansion].
AB  - OBJECTIVE: To study the effects of tissue expansion on tissue damage and
      retrograde degeneration. METHODS: 9 cases of conventional intermittent tissue
      expansion (CITE) and 9 cases of continuous pressure-controlled tissue expansion
      (CPTE) were chosen for the study. In creating of the expanded flaps, tissue
      samples were taken for histopathology, molecular biology and transmission
      electron microscope (TEM) examinations. RESULTS: Capillary bleeding, elastic and
      reticular fiber proliferation, arteriole thrombosis, fibroblast apoptosis and
      collagenolysis were observed after expansion. Retrograde degeneration was obvious
      in CITE group and acute lesion was obvious in CPTE group. CONCLUSION: Expansion
      stimulation induces tissue damage and retrograde degeneration, which indicates
      that the time for conventional intermittent expansion should be shortened and too
      fast continuous expansion is harmful.

PMID- 11838059
TI  - [Clinical study of a new expander with an agent delivery system and the effect of
      a chemical agent on tissue expansion].
AB  - OBJECTIVE: To search for a method to enhance tissue expansion. METHOD: A new type
      of expander with an agent delivery system was used to expand soft tissue in 15
      patients. During expansion Papaverine was delivered through the delivery system
      into the tissue around the expanders. RESULTS: It took 26 days to expand to the
      anticipated volume in the new expansion method group (NEM) and 51 days in the
      general expansion method group (GEM) (P < 0.01). Before operation the NEM group
      was over-expanded by 92.4% while the GEM group was over-expanded by 27.12%. At
      full expansion the blood flow of the expanded area of the two groups was 1.27
      (NEM) and 0.64 (GEM). The immediate skin retraction of the two groups was 20.17%
      (NEM) and 38.26% (GEM). CONCLUSION: The new expansion method can accelerate
      expansion speed and improve the quality of expanded skin and flap.

PMID- 11838060
TI  - [A primary clinical analysis of artificial bone implantation of cleft palate].
AB  - OBJECTIVE: To observe whether repairing the hard palate can improve
      velopharyngeal function. METHODS: 40 patients with hard palate cleft were
      randomly divided into two groups: the control group and the implantation group.
      Each group had 20 patients. The patients in the implantation group were implanted
      with compound artificial bone of HA--Bone cement. All patients hag been followed
      up for three months postoperatively. The patients in the repaired group were
      examined using computer tomography. All patients were examined using NPF.
      RESULTS: The implanted artificial bone had no rejection. The computer tomography
      showed that the implanted artificial bone in hard palate had no shifting,
      subsidence or breakage. The movement of soft palate of the implantation group was
      greater than the control group. The velopharyngeal function of the implantation
      group was much better than the control group. CONCLUSION: Repairing the hard
      palate cleft with artificial bone can improve velopharyngeal function.

PMID- 11838061
TI  - [Septorhinoplasty for nasal deviation complicated with septal cartilage
      deformity].
AB  - OBJECTIVE: To investigate a method for safe, simple and effective correction of
      nasal deviation complicated with the deformity of nasal septal cartilage.
      METHODS: From one side of the septal cartilage, the whole muco-perichondrium was
      separated, and from the other side a U-shaped muco-perichondrium was separated.
      The bottom of the septal cartilage was freed while a part of cartilage connected
      with the vomer was reserved. RESULTS: 12 patients were operated on with this
      technique for nasal deviation from March 1996 to August 1999. The follow-up
      period ranged from 1 to 12 months. The overall result was successful in all cases
      except one of recurrence. CONCLUSION: This technique not only provides wide space
      for removing the spetal cartilage, but also creates a cartilaginous framework to
      support the septal cartilage in the middle without lowing the nasal tip, which
      avoids the tendency of migrating to its original position caused by external
      fixation. This technique also ensures replacing the septal cartilage in the
      midline regardless of the deformity of anterior nasal spine and the vomer.

PMID- 11838062
TI  - [The experiences in correction of cicatricial foot drop in 28 patients].
AB  - OBJECTIVE: To summarize the experiences in correction of cicatricial foot drop.
      METHODS: 37 cicatricial drop feet in 28 postburn patients were treated in recent
      4 years. The cicatricial flap survival rate was documented to compare the effects
      of two surgical designs, the different intervals from burn to the operation and
      three surgical methods used in early burn stage. RESULTS: All of the 37 wounded
      feet got satisfactory correction. There was no significant statistic difference
      in flap survival between the two surgical designs. More necrosis of the flap was
      observed in patients who received early escharectomy (including full thickness
      skin and fat) or had been burned for less than 1.5 years. CONCLUSIONS: The
      reverse design of the Achilles tendon flap for correction of drop foot was as
      safe and effective as a routine design. The operation method used in early burn
      stage and the interval from burn to the corrective operation should be considered
      in cicatricial flap design.

PMID- 11838063
TI  - [An new filling material of hair for the application of plastic surgery].
AB  - OBJECTIVE: To investigate the possibility of hair as a filling material for
      reconstructive or cosmetic surgery. METHODS: Sterilized pellets of hairs and
      silicone were selected and implanted subcutaneously in white rabbits. The
      clinical trial was carried out in 3 cases. RESULTS: A thin fibrous capsule, with
      much few inflammatory cells, was formed around the implanted hair pellets in 3-4
      months. The inflammatory cells disappeared in the 9th month. No implant
      rejection, granulomatous formation or hair degradation was showed. CONCLUSION:
      Hair may be a valuable filling material for augmentation of the soft tissue.

PMID- 11838064
TI  - [The effect of L-arginine on the microcirculation reperfusion of cremaster muscle
      in rats].
AB  - OBJECTIVE: To investigate the effect of L-arginine and the role of nitric oxide
      (NO) on the microcirculation of cremaster muscle after the ischemia-reperfusion.
      METHODS: A group of male Sprague-Dawley rats, each weighing 180-220 g, were
      surgically prepared with the neurovascular bundle freed only to connect to the
      cremaster muscle, subjected to 5 hours warm ischemia and 2 hours of reperfusion,
      and treated with L-arginine. The microcirculation was observed with the
      measurement of the arteriole in diameter under intravital microscopy. RESULTS: 1.
      The arteriole re-flowing with the L-arginine treatment was significantly higher
      than the saline control with only 53% in 30 minutes after the reperfusion (P <
      0.01). 2. The diameter of the reflowed arteriole and the perfused capillary
      density were increasing greatly with the L-arginine treatment, compared to the
      control group. 3. The pathological phenomena of "only irrigation and no reflow"
      was observed in local muscle microcirculation, which subsequently resulted in the
      large-scale leakage hemorrhage. CONCLUSIONS: The nitric oxide product could
      relieve the vasospasm and decrease the no-reflow of skeletal muscular during
      reperfusion; The venular no-reflow resulted from venular thrombi may play an
      important part during the tissue reperfusion injury.

PMID- 11838065
TI  - [An experimental study of repairing nerve gap with acellular basal lamina tubes].
AB  - OBJECTIVE: To develop an effective new material for repair of nerve defects.
      METHODS: The 4-week pre-degenerative and normal sciatic nerve segments of SD rats
      were extracted with the detergent lysophosphatidylcholine, which resulted in
      acellular nerve basal lamina tubes, called EDNG (extracted degenerative nerve
      grafts) and ENG (extracted normal nerve grafts) respectively. The morphology of
      the acellular nerve basal lamina tubes was revealed by conventional histological
      examinations, transmission electron microscopy and immunohistochemistry method.
      The basal lamina tubes, as allografts, were used to repair a 15 mm-gap of sciatic
      nerve in Wistar rats. In the control group nerve autografts (NAG) was applied.
      Evaluation included general observation, electromyographic examination, muscle
      measurement and histological observation of serial sections at 12 weeks after
      surgery. RESULTS: The EDNG had more ideal frame, better resilience than ENG.
      There was no any cell debris in EDNG, whereas in the inner wall of the tubes
      immunohistochemical analysis revealed clear positive staining and strong
      immunoreactivity of laminin under immunoelectron microscopy. After peripheral
      nerves were repaired, all the animals of the three groups had restoration of
      function to a certain extent. The result of the NAG group was the best, the EDNG
      group was the next and the ENG group was the inferior. CONCLUSION: This new
      material offers a possible solution to repair of a short defect of a peripheral
      nerve.

PMID- 11838066
TI  - [Unequal distribution of health resources. Research is not supported with
      consideration to the global significance of the diseases].

PMID- 11838067
TI  - [We need our sleep!].

PMID- 11838068
TI  - [Andrology on the way to become a specialty of its own].

PMID- 11838069
TI  - [Sleep disorders--a public health problem. Potential risk factor in the
      development of type 2 diabetes, hypertension, dyslipidemia and premature aging].
AB  - A large proportion of the adult population complains over difficulties in falling
      asleep, difficulties in maintaining sleep, or early awakening. Despite the fact
      that sleep disorders may be secondary symptoms to established or subclinical
      disease processes, more and more evidence has now accumulated to support the
      notion that sleep disorders may also play a primary role in the pathophysiology
      of cardiovascular disease. This has recently been documented in association with
      metabolic disturbances and impaired insulin action following experimental sleep
      deprivation. Sleep disorders may finally prove to be part of the
      pathophysiological chain linking adverse psychosocial stress with the metabolic
      syndrome, and ultimately premature ageing and early mortality.

PMID- 11838070
TI  - [Report from the congress on andrology in Montreal. Diagnosis and treatment of
      the "andropause"].
AB  - As reflected by the proceedings of the recent VIIth International Congress of
      Andrology in Montreal, Canada, modern andrology takes a wider responsibility for
      men's health than previously. The area has expanded not only into the fields of
      basal and clinical endocrinology but also into paediatrics and geriatrics. These
      changes also put pressure on laboratories of clinical chemistry to provide new
      and clinically more relevant endocrinological investigations such as lutropin
      assays which detect the biologically active isoforms, and assays of
      "bioavailable" testosterone, as well as of inhibin B and anti-Mullerian hormone.

PMID- 11838071
TI  - [A child's growth mirrors health and illness. Regular measurement of body height
      is an important diagnostic tool].
AB  - The growth of children is an important health indicator. In the individual child,
      growth mirrors health or illness. At the child population level, growth may be
      used to monitor living conditions. Continued deviations may indicate somatic
      disorders or psychosocial problems. The assessment of the growth of an individual
      child is complicated due to the difficulty to measure children. Thus, the height
      of the child will have to deviate substantially from that of the reference
      population before action is called for. The progress over time of the child's
      growth, on the other hand, is a much more sensitive indicator of ill health than
      is the height of the child at a certain age. Systematic assessment of each
      measuring may serve as an aid to detect abnormal growth and thereby facilitate a
      correct diagnosis.

PMID- 11838073
TI  - [Prophylaxis against RS virus infection].

PMID- 11838074
TI  - [Functional gastrointestinal diseases. Psychotherapy is an efficient complement
      to drug therapy].
AB  - An emerging body of data support the efficacy of psychological treatments in
      functional gastrointestinal disorders. Twenty-two studies that used a controlled
      design to compare psychological treatment with conventional medical treatment
      and/or supportive therapy were reviewed. Most of the research to date has focused
      on irritable bowel syndrome. In terms of reduction of bowel symptoms, 19 studies
      showed statistically significant superiority of psychological over conventional
      treatment at the end of treatment and/or at follow-up. Of 12 studies with follow
      up data, 8 showed superiority of psychological treatment. Another 8 studies with
      follow-up data only for those who received psychotherapy, showed further
      improvement or that gains were maintained after completion of treatment. In
      conclusion, psychological treatment appears superior to conventional treatment.
      Successful outcomes have been observed with dynamic psychotherapy, hypnosis,
      cognitive-behavior therapy, and relaxation training. Differences in outcomes
      based on specific treatment techniques have not been studied. Thus, given the
      current state of knowledge, psychotherapists should use the technique with which
      they are most experienced.

PMID- 11838072
TI  - [Growth rate can be manipulated. Estrogen production in pubertal boys can be
      blocked by an aromatase inhibitor].
AB  - A review of a twelve month clinical trial [1] using a new, effective aromatase
      inhibitor treatment in boys with delayed puberty shows that the pubertal increase
      in estrogen levels can be blocked, with concomitant preserved pubertal growth
      rate. Circulating testosterone levels are greatly enhanced during treatment due
      to increased gonadotrophin secretion. Despite this, bone age maturation is slow
      leading to an increased final height prognosis (mean 5.1 cm) for the boys treated
      with aromatase inhibitor.

PMID- 11838075
TI  - [Are supervisors affected by training? An assessment of 8 years with courses for
      physicians].

PMID- 11838076
TI  - [Discussing tissue donation with relatives of deceased patients is difficult.
      Interview study among physicians].
AB  - The current Swedish transplant act (1995:831), which in contrast to the former
      law covers the procurement of tissues came into force on July 1, 1996. Eleven
      doctors and nurses were interviewed concerning their experiences of discussing
      tissue donation with bereaved relatives. The interviews revealed that breaking
      news about a patient's death was considered a routine matter, whereas discussing
      donation with relatives was regarded a difficult and unpleasant task. In general,
      the medical staff was not sufficiently familiar with the new law, and reported
      the lack of routines and guidelines in these matters as a problem. Many of the
      doctors felt they needed more psychological support and more opportunities to
      discuss ethical questions; the nurses asked for more information about donation
      and transplantation, and about ethics. In conclusion, there is a need for
      training in the communication skills involved in approaching bereaved relatives
      on the subject of tissue donation. There is also a need for a better
      understanding of the importance of providing psychological support to medical
      staff on the part of chiefs and health care authorities.

PMID- 11838077
TI  - [Counterproductive elements in current emergency care of psychoses. The care must
      support the healing process].

PMID- 11838078
TI  - [Surprising conclusion by the SBU concerning the benefits of naltrexone in the
      treatment of heroin dependence].

PMID- 11838079
TI  - [Sick or injured abroad: Is home transportation with the SOS-International up to
      the 2001 level?].

PMID- 11838080
TI  - [SOS-International answers: Collum fracture is usually nailed locally. Air
      ambulance should be extremely expensive].

PMID- 11838081
TI  - [Simulator endoscopic training should be included in medical education].

PMID- 11838082
TI  - [Are there any cost-benefit limits in connection with neonatal care?].

PMID- 11838083
TI  - [Estrogen, risk of fracture and osteoporosis].

PMID- 11838084
TI  - [Does right-wing health policy counteract private practitioners?].

PMID- 11838085
TI  - [Warning against the ice hat].

PMID- 11838086
TI  - [Patient safety within insurance medicine].

PMID- 11838087
TI  - The perioperative nurse's gift in organ recovery.

PMID- 11838088
TI  - Hysteroscopic surgery.

PMID- 11838089
TI  - Herbal medications.

PMID- 11838090
TI  - The perioperative nurse and the organ donation experience.
AB  - Most OR nurses whether veteran or novice have had some exposure to organ
      donation; however, few are aware of what occurs outside of the surgical setting.
      This article provides an overview of the entire donation process, from the hours
      before the procedure to the steps needed for successful recovery. Particular
      attention is given to the care of the donor family members, both preoperatively
      and postrecovery.

PMID- 11838091
TI  - Snoring and obstructive sleep apnea.
AB  - The most common form of sleep apnea is obstructive sleep apnea (OSA). It is
      characterized by the cessation of nasal airflow with persistence of ventilatory
      effort, as shown by paradoxical chest and abdominal movement, and varying degrees
      of oxygen desaturation. This article describes current methods of diagnosing OSA
      and available treatment for OSA and snoring.

PMID- 11838092
TI  - Lymphatic mapping and sentinel lymph node biopsy.
AB  - Malignant melanoma--cancer of the pigment cells--has the highest mortality rate
      of all skin cancers. With early detection and treatment, however, malignant
      melanoma is highly curable. Recently, diagnostic modalities for nodal involvement
      have been perfected, reducing the morbidity of elective lymph node dissections
      and rendering them unnecessary in many cases. Total lymphadenectomy procedures
      are being replaced by intraoperative lymphatic mapping and sentinel lymph node
      biopsy using gamma detector probes. This article reviews lymphatic drainage from
      the primary site to possible lymph node basins and selective lymph node
      dissection using lymphoscintigraphy and intraoperative mapping as guides. This
      article also includes a case study, beginning with a diagnosis of malignant
      melanoma and following a successful postoperative course.

PMID- 11838094
TI  - Stomach tumors and gastric surgery.
AB  - Malignant and benign tumors of the stomach must be resected. Some can be removed
      endoscopically, but larger lesions must be removed via traditional surgical
      methods. This article provides an overview of malignant and benign stomach tumors
      and outlines the determination of diagnosis and the recommended treatment. It
      describes different types of gastric surgery and the RN first assistant's role in
      these procedures. A case study of a rare type of benign stomach tumor also is
      presented.

PMID- 11838093
TI  - A multidisciplinary approach to breast biopsy.
AB  - The explosion in technological advances has provided physicians and patients more
      options in the diagnostic breast biopsy arena. Successful collaborative
      relationships between nurses, physicians, and all health care workers and
      detailed patient education are essential to provide optimum patient care.
      Survival in health care today mandates that perioperative nurses and their
      colleagues move outside traditional environments to provide quality, cost
      effective care to patients and their family members. The aim of this
      collaborative approach to breast biopsy is to provide patients with the most
      expedient, accurate, cost-effective diagnoses with the least amount of physical
      and psychological trauma.

PMID- 11838095
TI  - Recommended practices for surgical hand scrubs.

PMID- 11838096
TI  - Successful delegation skills enhance patient care.

PMID- 11838097
TI  - A primer on causality in research.

PMID- 11838098
TI  - Contemporary psychoanalysis in relation to analytical psychology: introduction
      and questionnaire.

PMID- 11838099
TI  - The myth of pure analysis.

PMID- 11838100
TI  - A relational self psychological perspective.

PMID- 11838101
TI  - Freud and Jung: the boundaried mind and the radically connected mind.

PMID- 11838102
TI  - [Wegener's granulomatosis].

PMID- 11838103
TI  - [Goodpasture syndrome].

PMID- 11838104
TI  - [Sleep apnea syndrome].

PMID- 11838105
TI  - [Epidemiology of reflux esophagitis].

PMID- 11838106
TI  - [Gastric ulcer].

PMID- 11838108
TI  - [Crohn's disease].

PMID- 11838107
TI  - [Duodenal ulcer].

PMID- 11838109
TI  - [Ulcerative colitis].

PMID- 11838110
TI  - [Chronic obstructive pulmonary disease].

PMID- 11838111
TI  - [Ischemic colitis].

PMID- 11838112
TI  - [Epidemiological data of irritable bowel syndrome].

PMID- 11838113
TI  - [Colorectal polyp].

PMID- 11838114
TI  - [Malabsorption].

PMID- 11838115
TI  - [Hepatitis A].

PMID- 11838116
TI  - [Hepatitis B].

PMID- 11838117
TI  - [Hepatitis C].

PMID- 11838118
TI  - [The incidence of alcoholic liver disease in Japan].

PMID- 11838119
TI  - [Drug-induced liver injury].

PMID- 11838120
TI  - [Liver cirrhosis: statistics in Japan].

PMID- 11838121
TI  - [Interstitial pneumonia, pulmonary fibrosis].

PMID- 11838122
TI  - [Primary biliary cirrhosis].

PMID- 11838123
TI  - [Idiopathic portal hypertension].

PMID- 11838124
TI  - [Fatty liver].

PMID- 11838125
TI  - [Autoimmune hepatitis].

PMID- 11838126
TI  - [Constitutional hyperbilirubinemia].

PMID- 11838128
TI  - [Biliary infection].

PMID- 11838129
TI  - [Acute pancreatitis].

PMID- 11838127
TI  - [Cholelithiasis].

PMID- 11838130
TI  - [Chronic pancreatitis].

PMID- 11838131
TI  - [H. pylori infection].

PMID- 11838132
TI  - [Pustular psoriasis and psoriasis vulgaris].

PMID- 11838133
TI  - [Diffuse panbronchiolitis (DPB)].

PMID- 11838134
TI  - [Stevens-Johnson syndrome].

PMID- 11838135
TI  - [Rheumatoid arthritis].

PMID- 11838137
TI  - [Polyarteritis nodosa, microscopic polyangiitis].

PMID- 11838136
TI  - [(Clinical data of) adult Still's disease].

PMID- 11838138
TI  - [Takayasu arteritis (aortitis syndrome)].

PMID- 11838139
TI  - [Systemic lupus erythematosus].

PMID- 11838141
TI  - [Systemic sclerosis (SSc)].

PMID- 11838140
TI  - [Polymyositis, dermatomyositis].

PMID- 11838142
TI  - [Sjogren's syndrome].

PMID- 11838143
TI  - [Behcet's disease].

PMID- 11838144
TI  - [Weber-Christian disease].

PMID- 11838145
TI  - [Mixed connective tissue disease].

PMID- 11838146
TI  - [Antiphospholipid syndrome].

PMID- 11838147
TI  - [Ankylosing spondylitis].

PMID- 11838148
TI  - [Osteoporosis: the Japanese clinical statistical data].

PMID- 11838149
TI  - [Acute glomerulonephritis].

PMID- 11838150
TI  - [Rapidly progressive glomerulonephritis].

PMID- 11838151
TI  - [IgA nephropathy].

PMID- 11838152
TI  - [Henoch-Schonlein purpura nephritis].

PMID- 11838153
TI  - [Epidemiology of bronchial asthma in Japan].

PMID- 11838154
TI  - [ANCA related (associated) glomerulonephritis].

PMID- 11838155
TI  - [Clinical and epidemiological data of nephrotic syndrome in Japan].

PMID- 11838157
TI  - [Tubulointerstitial nephritis].

PMID- 11838156
TI  - [Hereditary nephritis].

PMID- 11838158
TI  - [Drug induced nephropathy].

PMID- 11838159
TI  - [Clinical aspect of acute renal failure in recent years].

PMID- 11838160
TI  - [Chronic renal failure].

PMID- 11838161
TI  - [Nephrogenic diabetes insipidus].

PMID- 11838162
TI  - [Bronchial asthma in childhood].

PMID- 11838163
TI  - [Renal tubular acidosis (RTA)].

PMID- 11838165
TI  - [Autosomal dominant polycystic kidney].

PMID- 11838166
TI  - [Urolithiasis].

PMID- 11838164
TI  - [Bartter syndrome, Gitelman syndrome, Liddle syndrome].

PMID- 11838167
TI  - [Urinary tract infection].

PMID- 11838169
TI  - [A statistical study of benign prostatic hyperplasia in Japan].

PMID- 11838168
TI  - [Sexually transmitted diseases].

PMID- 11838171
TI  - [Hemolytic uremic syndrome, thrombotic thrombocytopenic purpura].

PMID- 11838170
TI  - [Erectile dysfunction].

PMID- 11838172
TI  - [Progeroid syndromes].

PMID- 11838174
TI  - [Klinefelter syndrome].

PMID- 11838173
TI  - [Turner syndrome].

PMID- 11838175
TI  - [Sick house syndrome].

PMID- 11838176
TI  - [Pesticide poisoning].

PMID- 11838177
TI  - [Malignant hyperthermia].

PMID- 11838179
TI  - [Pollinosis].

PMID- 11838178
TI  - [Acute respiratory distress syndrome (ARDS)].

PMID- 11838180
TI  - [Atopic dermatitis].

PMID- 11838181
TI  - [Drug allergy].

PMID- 11838182
TI  - [Retinitis pigmentosa].

PMID- 11838183
TI  - [Menetriere's disease].

PMID- 11838185
TI  - [Renal transplantation].

PMID- 11838186
TI  - [Liver transplantation].

PMID- 11838184
TI  - [Dialysis therapy].

PMID- 11838187
TI  - [Bacterial pneumonia].

PMID- 11838188
TI  - [Heart transplantation].

PMID- 11838189
TI  - [Lung transplantation].

PMID- 11838190
TI  - [Hematopoietic stem cell transplantation].

PMID- 11838191
TI  - [Post-transfusion GVHD].

PMID- 11838192
TI  - [Measures against intractable diseases].

PMID- 11838194
TI  - [Meningitis].

PMID- 11838193
TI  - [Measles].

PMID- 11838195
TI  - [Hypersensitivity lung and PIE syndrome].

PMID- 11838196
TI  - [Hyperventilation syndrome].

PMID- 11838197
TI  - [Pneumoconiosis].

PMID- 11838198
TI  - [Sarcoidosis].

PMID- 11838199
TI  - Antibodies to granulocytic Ehrlichia in moose, red deer, and roe deer in Norway.
AB  - Serum samples from 104 moose (Alces alces), 124 red deer (Cervus elaphus) and 114
      roe deer (Capreolus capreolus), collected from different counties in southern
      Norway from 1994 to 2000, were analysed by an indirect immunofluorescent antibody
      staining method for antibodies to Ehrlichia equi. The overall seroprevalences for
      granulocytic Ehrlichia spp. in moose, red deer, and roe deer from Ixodes ricinus
      infested counties were 43%, 55%, and 96%, respectively. Antibody prevalence was
      significantly higher in roe deer than in moose and red deer (P < 0.001). Mean
      antibody titers (log10 +/- SD) to E. equi in sera from moose, red deer, and roe
      deer were 1:1,497 (3.17 +/- 0.646), 1:234 (2.37 +/- 0.424) and 1:676 (2.83 +/-
      0.404), respectively. The present work indicates that all these wild ruminant
      species are exposed to granulocytic Ehrlichia in Norway.

PMID- 11838200
TI  - Retrospective study of morbidity and mortality of raptors admitted to Colorado
      State University Veterinary Teaching Hospital during 1995 to 1998.
AB  - A retrospective study was conducted to identify causes of morbidity and mortality
      of free-living raptors in northeast Colorado and the surrounding areas of
      Nebraska and Wyoming. The study included 409 raptors, representing 23 species,
      admitted to the Colorado State University Veterinary Teaching Hospital, Fort
      Collins, Colorado, USA, from 1995 to 1998. Causes of morbidity and mortality were
      identified as trauma (66.3%), orphaned young (15.6%), unknown (9.0%), infectious
      disease (4.4%), metabolic and nutritional disease (2.2%), toxicosis (2.0%), and
      degenerative disease (0.5%). Trauma was the most frequent cause of morbidity and
      mortality for all species and during all seasons.

PMID- 11838201
TI  - Causes of mortality of free-ranging Florida panthers.
AB  - The Florida panther (Puma concolor coryi) is one of the most endangered mammals,
      with the entire population estimated to consist of only 30-50 adult animals.
      Between 1978 and 1999, 73 free-ranging Florida panther carcasses were submitted
      for postmortem evaluation, of which 47 (64%) were radiocollared and 26 (36%) were
      uncollared cats. Overall, mortality of panthers > 6-mo-old was due to vehicular
      trauma in 25 (35%), intraspecific aggression in 19 (26%), illegal kill in seven
      (10%), research activities in two (3%), infectious diseases in two (3%),
      esophageal tear in one (1%), pleuritis in one (1%), pyothorax in one (1%), aortic
      aneurysm in one (1%), atrial septal defect in one (1%), and causes of death were
      undetermined in 13 (18%) due to autolysis. Of the 25 panthers that were killed by
      vehicular trauma, 20 (80%) died between October and April. This coincides with
      increased number of winter visitors to south Florida. Among radiocollared
      panthers, intraspecific aggression was the primary cause of mortality for 19
      (41%) dead cats. Of these cats, 16 (84%) were males and 14 (88%) were either less
      than 3 or more than 8-yr-old. These animals were probably fighting to establish
      or retain territory. Among the 26 uncollared panthers, vehicular trauma was the
      primary cause of mortality and was responsible for 16 (62%) deaths. This study
      documents the causes of mortality and the age, sex, and seasonal mortality trends
      for both radiocollared and uncollared free-ranging endangered Florida panthers
      over a 21-yr-period.

PMID- 11838202
TI  - Retrospective study of proliferative papillary vulvitis in Florida panthers.
AB  - Proliferative, papillary vulvitis was identified in 16 of 34 (47%) free-ranging
      and captive female Florida panthers (Puma concolor coryi) monitored over a period
      from 1983-98. Gross lesions were characterized by extensive papilliferous
      proliferation in the mucosa of the vestibulum vaginae. Within lesions, the mean
      length and width of vestibular papillae were 1.07 +/- 0.39 mm (CV = 36%) and 0.55
      +/- 0.11 mm (CV = 20%) respectively. Histologically, three to 12 layers of non
      cornified stratified squamous epithelium with various degrees of basal cell
      spongiosis and rete ridge formation covered fibrous papillae. Mixed leukocytic
      mucosal inflammation also was observed. Infectious organisms were not observed,
      and immunohistochemical testing for the presence of papillomavirus antigens in
      specimens from seven panthers was negative. Lesions in nearly all of the panthers
      were first observed during a six-year period (1986-92), with one each in 1983,
      1996 and 1998. There were no significant differences between the number of
      females having litters, the number of litters between age-matched and interval
      matched females, and the interval between litters among lesions positive and
      lesion negative females over the 15 yr period. The severity of lesions did not
      appear to differ between parous and nulliparous free-ranging lesion-positive
      females. The cause of proliferative vulvitis remains unknown. However, the lesion
      did not appear to have a significant effect on reproduction.

PMID- 11838203
TI  - Salt toxicosis in ruddy ducks that winter on an agricultural evaporation basin in
      California.
AB  - Agricultural evaporation basins are used as a means to dispose of highly saline
      underground-tile-drainage water in the San Joaquin Valley (California, USA). The
      hypersaline water conditions encourage high aquatic invertebrate production,
      primarily brine shrimp (Artemia franciscana), which attract birds to these sites.
      Cool winter temperatures (< 4 C) and hypersaline water conditions (> 70,000
      mumhos/cm) resulted in feather salt encrustation and salt toxicosis in ruddy
      ducks (Oxyura jamaicensis). During December 1998 and January 1999, approximately
      200 dead and sick ruddy ducks were collected from an evaporation basin and five
      healthy control ruddy ducks were collected from a freshwater wetland. Brains
      contained > or = 1,890 ppm sodium (wet tissue mass) in seven dead birds and
      contained < or = 1,150 ppm sodium in the control birds. Liver arsenic, lead, and
      mercury concentrations were < 1 ppm in all birds examined. Manganese, molybdenum,
      and copper liver concentrations did not differ significantly (P > 0.05) between
      the two groups of ducks. The dead ducks had significantly higher liver selenium,
      cadmium, iron, and zinc than the controls, but the concentrations were not
      sufficient to cause toxicity. Significant gross and microscopic lesions in most
      of the dead birds included conjunctivitis, lens opacity and cataract formation,
      vascular congestion in various organs most notably in the meninges of the brain,
      and myocardial and skeletal muscle degeneration.

PMID- 11838204
TI  - Essential fatty acid profiles differ across diets and browse of black rhinoceros.
AB  - In captivity, black rhinoceros (Diceros bicornis) suffer from idiopathic skin
      lesions that may be linked to dietary deficiencies, in particular essential fatty
      acid deficiency (EFAD). Therefore, a study was undertaken from July 1995 to May
      1997 to characterize the diet of captive D. bicornis in North American zoos and
      measure fat and fatty acid composition in zoo diet, and African and North
      American browses. Descriptions of all dietary items offered to black rhinos on a
      daily basis were compiled from 20 North American zoos; zoo diet contained (mean
      +/- SE) 61 +/- 2% hay, 28 +/- 2% grain pellets, 6 +/- 1% produce, and 5 +/- 1%
      fresh browse, with hay and grain pellets together comprising nearly 90% of items
      offered. Gas chromatography-mass spectrometry analysis (GC-MS) was used to
      measure triacylglycerol equivalent (TAG), total fatty acids (TFA), and essential
      fatty acids (EFA) in zoo diet, and African and North American browses. North
      American browse contained more TAG and TFA than did zoo diet or African browse.
      Zoo diet contained more linoleic acid (18:2n6) and less linolenic acid (18:3n3)
      than either African browse corrected for degradation losses or North American
      browse, whether measured as weight percentage of dry sample or as weight
      percentage of TFA. In addition, the ratio of 18:2n6 to 18:3n3 was significantly
      lower in both browses than in zoo diet. There are significant nutritional
      differences between the major dietary components of North American captive black
      rhinoceros diets and native African browses that warrant further exploration
      given the health problems associated with this animal in captivity.

PMID- 11838205
TI  - Hematology and plasma biochemistry reference range values for free-ranging desert
      tortoises in Arizona.
AB  - Baseline values and ranges for 10 hematologic and 32 plasma chemistry parameters
      were analyzed for 36 free-ranging Sonoran desert tortoises (Gopherus agassizzi)
      collected in Yavapai and La Paz Counties (Arizona, USA) from 1990 to 1995.
      Tortoises were radio tagged from 1990 to 1994, and attempts were made to
      recapture them three times a year. Tortoises were weighed, measured, and
      chemically immobilized to collect blood for hematology and blood chemistry
      assessments. Tortoise biochemistry differed (P < 0.01) between sites and sexes
      and among seasons and years. Normal reference ranges for hematologic and plasma
      biochemistry parameters were determined. Seasonal and annual differences in
      hematology and blood chemistry were related to rainfall patterns, forage
      availability, and physiological condition.

PMID- 11838206
TI  - Plasma chemistry reference values in ostriches.
AB  - Reference values for 18 plasma chemical variables in blue neck ostriches
      (Struthio camelus australis, n = 60, age 24-36 mo) were established for use in
      veterinary clinical practice using nonparametric statistics. The following values
      were established for the percentiles P2.5 and P97.5: sodium 147-157 mmol/L,
      calcium 2.4-4.8 mmol/L, inorganic phosphate 1.3-2.3 mmol/L, chloride 94-105
      mmol/L, glucose 10.3-13.7 mmol/L, urea 0.5-0.8 mmol/L, uric acid 351-649 mumol/L,
      bile acids 8-33 mumol/L, total protein 39-56 g/L, albumin-globulin ratio 0.45
      0.59, osmolality 304-330 mOsm/kg, alkaline phosphate 69-217 IU/L, aspartate
      aminotransferase 243-418 IU/L, gamma-glutamyltransferase 0-1 IU/L, creatine
      kinase 1648-4894 IU/L, glutamate dehydrogenase 8-17 IU/L, and lactate
      dehydrogenase 860-2236 IU/L. The plasma calcium concentration was significantly
      (P < 0.001; r = 0.74) related to the total protein concentration and an
      adjustment-formula for calcium was derived: adjusted Ca (mmol/L) = Ca (mmol/L)-
      0.09 TP (g/L) + 4.4. The influence of blood sample treatment on the plasma
      potassium concentration as seen in other avian species was demonstrated in a
      separate experiment, emphasizing the need to separate plasma and cells
      immediately after collection in avian blood samples.

PMID- 11838207
TI  - Detection by microsatellite analysis of early embryonic mortality in an alligator
      population in Florida.
AB  - In the 1980s, alligators (Alligator mississippiensis) of Lake Apopka (Florida,
      USA) underwent a population decline associated with decreased egg viability,
      effects that have been associated with endocrine-disrupting, persistent
      organochlorine pesticides. It is currently unknown whether the decreased egg
      viability is due to fertilization failure or early embryonic death. Therefore, we
      conducted a preliminary study to evaluate the use of microsatellite DNA loci to
      determine the fertilization status of nonviable eggs. Using microsatellite
      analysis, we compared genotypes from blasto-disks and embryos with the genotypes
      from females trapped at the nest. Four of five nonviable egg samples tested
      yielded evidence of fertilization. No evidence of unfertilized eggs was obtained,
      but amplifiable DNA could not be obtained from one entirely nonviable clutch.
      Thus, we demonstrate that early embryonic mortality in alligators can be detected
      by microsatellite analysis, but also suggest substantial effort is needed to
      improve the recovery of DNA and amplification of alligator microsatellite loci.

PMID- 11838208
TI  - Oral and fecal shedding of epizootic hemorrhagic disease virus, serotype 1 from
      experimentally infected white-tailed deer.
AB  - Epizootic hemorrhagic disease (EHD), one of the most important infectious
      diseases of white-tailed deer (Odocoileus virginianus), is vectored by species of
      midges in the genus Culicoides. Although vector borne, fecal shedding of EHD
      virus, serotype 2 has been reported from infected deer in a previous study. To
      evaluate the potential for fecal and oral shedding, oral and rectal swabs were
      obtained on day 8 post-inoculation from white-tailed deer fawns experimentally
      infected with EHD virus, serotype 1 (EHDV-1). Eight deer were viremic for EHDV-1;
      virus was detected in oral swabs from three (38%) and in rectal swabs from four
      (50%). The ability to isolate EHDV-1 in oral secretions or feces was not
      dependent on being able to detect clinical disease. These results indicate that
      in a relatively large proportion of EHDV-1 infected deer, virus can be detected
      in feces and oral secretions. Although more work is necessary, such shedding may
      be important in experimental studies or pen situations where deer-to-deer contact
      is prevalent and intense.

PMID- 11838209
TI  - Serosurvey for Newcastle disease and avian influenza A virus antibodies in great
      cormorants from France.
AB  - Inland great cormorants (Phalacrocorax carbo) culled in France were examined in
      the winter of 1997-98 and 1998-99 for antibodies to Newcastle disease (ND) and
      influenza A strains H5 and H7 by the hemagglutination inhibition test. Antibodies
      to influenza A group antigen were tested by agar gel precipitin test. Ten of 53
      adult individuals were seropositive for ND virus. All sera were negative for
      influenza A antibodies. It is speculated that ND occurred in the sampled
      population.

PMID- 11838210
TI  - Hemorrhagic disease in bighorn sheep in Arizona.
AB  - Two bighorn sheep from Arizona (USA) were submitted for necropsy. One was a Rocky
      Mountain bighorn (Ovis canadensis canadensis) and the other was a desert bighorn
      (Ovis canadensis mexicana). Both had lesions consistent with those of hemorrhagic
      disease (HD). Epizootic hemorrhagic disease virus (EHDV) type-2 and bluetongue
      virus (BTV) type-17, respectively, were isolated from the sheep tissues. To our
      knowledge, HD caused by either EHDV or BTV infection has not been documented
      previously in Arizona bighorn sheep.

PMID- 11838211
TI  - Hemorrhagic disease in deer in Arizona.
AB  - Two mule deer (Odocoileus hemionus) and one white-tailed deer (Odocoileus
      virginianus) in Arizona (USA) were submitted for necropsy. Gross and microscopic
      lesions compatible with hemorrhagic disease (HD) were observed in all three deer.
      Epizootic hemorrhagic disease virus type 2 (EHDV-2) was isolated from two of the
      deer. To our knowledge, this is the first documentation of HD in deer in Arizona.
      Two of the mortalities were attributed to EHDV-2 infection.

PMID- 11838212
TI  - Brucella abortus strain RB51 vaccination in elk. I. Efficacy of reduced dosage.
AB  - Bovine brucellosis is a serious zoonotic disease affecting some populations of
      Rocky Mountain elk (Cervus elaphus nelsoni) and bison (Bison bison) in the
      Greater Yellowstone Area, USA. The fear that elk and/or bison may spread Brucella
      abortus to livestock has prompted efforts to reduce or eliminate the disease in
      wildlife. Brucella abortus strain RB51 (RB51) vaccine has recently been approved
      for use in cattle. Unlike strain 19 vaccine, RB51 does not cause false positive
      reactions on standard brucellosis serologic tests. If effective, it may become
      the vaccine of choice for wildlife. In February 1995, 45 serologically negative
      female elk calves were trapped and taken to the Sybille Wildlife Research and
      Conservation Education Unit near Wheatland, Wyoming, USA. In May 1995, 16 of
      these elk calves were hand-vaccinated with 1 x 10(9) colony forming units (CFU)
      of RB51, 16 were vaccinated with 1 x 10(8) CFU RB51 by biobullet, and 13 were
      given a saline placebo. The elk were bred in fall of 1996 and they were
      challenged with 1 x 10(7) CFU of B. abortus strain 2308 by intraconjunctival
      inoculation in March 1997. Thirteen (100%) control elk aborted, 14 (88%) hand
      vaccinated elk aborted, and 12 (75%) biobullet vaccinated elk aborted or produced
      nonviable calves. These results suggest that a single dose of 1 x 10(8) to 1 x
      10(9) CFU RB51 does not provide significant protection against B. abortus induced
      abortion in elk. However, the vaccine appears to be safe at this dose and
      additional study may reveal a more effective RB51 vaccine regimen for elk.

PMID- 11838213
TI  - Leptospiral antibodies in flying foxes in Australia.
AB  - The sera of 271 pteropid bats (or flying foxes) collected from Queensland, New
      South Wales, Western Australia, and the Northern Territory were screened against
      a reference panel of 21 Leptospira spp. using the microscopic agglutination test
      (MAT). Sera were collected from December 1997 through August 1999. The MAT panel
      represented those serovars previously isolated in Australia, as well as exotic
      serovars found in neighboring countries. Leptospiral antibodies were detected in
      75 (28%) of the sera and represented seven serovars, one of which, L. interrogans
      serovar cynopteri has been regarded as exotic to Australia. Sixty sera were
      reactive to one serovar, 12 sera were reactive to two serovars, and three sera
      were reactive to three serovars. The L. kirschneri serovar australis was most
      frequently identified (60.2%). The findings suggest a previously unrecognized
      role of pteropid bats in the natural history of leptospirosis. The potential
      exists for establishment of infection in new host species, the transmission of
      new serovars to known host species, and for changes in virulence of leptospires
      as a result of passage through these species.

PMID- 11838214
TI  - Fatal spirochetosis due to a relapsing fever-like Borrelia sp. in a northern
      spotted owl.
AB  - Acute septicemic spirochetosis was diagnosed in an adult male northern spotted
      owl (Strix occidentalis caurina) found dead in Kittitas County, Washington, USA.
      Gross necropsy findings included marked enlargement of the liver and spleen and
      serofibrinous deposits on the serous membranes lining the body cavities and the
      pericardial and perihepatic sacs. Microscopic observations included macrophage
      infiltration in the liver and spleen with mild thrombosis and multifocal
      necrosis, as well as hemorrhage and acute inflammation in the choroid plexus of
      the brain. No viruses or pathogenic bacteria were isolated from brain, liver, or
      spleen, and no parasites were found in blood smears or impression smears of the
      liver. Chlamydial culture attempts were unsuccessful and no chlamydial antibodies
      were detected in serum. In silver-stained microscopic sections and by
      transmission electron microscopy of liver, numerous long, thin, spiral-shaped
      bacteria were seen in the liver, spleen, cerebral ventricles, and within blood
      vessels in many organs. The organism was identified as a member of the Borrelia
      genus by sequence analysis of the PCR-amplified 16S rRNA gene. The most closely
      related species is B. hermsii, an agent of relapsing fever in humans in the
      western United States. This is the first report of a relapsing fever-related
      Borrelia in a wild bird.

PMID- 11838215
TI  - Experimental infection of dusky-footed wood rats (Neotoma fuscipes) with
      Ehrlichia phagocytophila sensu lato.
AB  - Dusky-footed wood rats, Neotoma fuscipes, have been implicated in the natural
      maintenance of Ehrlichia phagocytophila sensu lato, the agent of human
      granulocytic ehrlichiosis (HGE), in northern California based on high
      seroprevalence and amplification of E. phagocytophila s.l. DNA from wood rat
      blood. In order to further assess granulocytic ehrlichiosis in wood rats, we
      examined wild-caught wood rats for infection and then performed experimental
      intra-peritoneal infections with E. phagocytophila s.l. in horse or wood rat
      blood, and tested animals for 120 days by polymerase chain reaction (PCR) and
      serology. Of 15 wood rats collected from northern California, three were antibody
      and PCR-positive for E. phagocytophila s.l. at the time of capture. The naturally
      infected wood rats remained PCR-positive for a mean of 52 days (+/- 7 SD).
      Experimental i.p. passage of E. phagocytophila s.l. in wood rat blood was
      successful in three of four wood rats and the mean duration of PCR-positivity was
      75 days (+/- 21.2 SD). Experimental infection with E. phagocytophila s.l. in
      horse blood succeeded in all four of the recipients and the mean duration of PCR
      positivity of 81 days (+/- 17.5 SD). No infected individual appeared to be ill
      based on feeding behavior, activity, and hydration status. These data confirm
      that wood rats are susceptible to E. phagocytophila s.l., may develop prolonged
      infection without clinical ehrlichiosis, and may play a role in maintaining E.
      phagocytophila s.l. in nature.

PMID- 11838216
TI  - Morganelliasis pneumonia in a captive jaguar.
AB  - Suppurative bronchopneumonia was discovered in a 6-yr-old male jaguar (Panthera
      onca onca) that died after a 1 wk history of anorexia, depression, and
      respiratory difficulty. Morganella morganii was isolated as a pure culture from
      the lung, spleen, and heart blood. This is the first record of M. morganii
      induced pneumonia in a jaguar.

PMID- 11838217
TI  - Occurrence of yersiniosis and listeriosis in wild boars in Japan.
AB  - From December 1994 to February 1995, 131 wild boars (Sus scrofa leucomysta)
      living in a mountainous area in Japan were examined for yersiniosis and
      listeriosis. Of 131 wild boars, 76 (58%) were males and 55 (42%) were females.
      Four Yersinia spp. including Y. pseudotuberculosis, Y. enterocolitica, Y.
      frederiksenii, and Y. aldovei, were isolated from 49 (37%) of 131 wild boars.
      Yersinia pseudotuberculosis was isolated from five (4%) of 131 wild boars. All Y.
      pseudotuberculosis isolates were serotype 4b and harbored virulence plasmids.
      Yersinia pseudotuberculosis was isolated only from boars under 2-yr-old. No human
      pathogenic Y. enterocolitica was isolated. Listeria monocytogenes was isolated
      from two (1%) of the wild boars and both isolates were serotype 4b. These
      findings indicated that wild boar could be a reservoir of Y. pseudotuberculosis
      and L. monocytogenes in Japan.

PMID- 11838218
TI  - Chytridiomycosis in native Arizona frogs.
AB  - Twenty-seven adult/sub-adult lowland leopard frogs (Rana yavapaiensis), two
      larval lowland leopard frogs, two adult Chirichahua leopard frogs (Rana
      chiricahuensis), and two adult canyon tree frogs (Hyla arenicolor) collected from
      populations experiencing mortality events at eight sites were found to have
      characteristic lesions of chytrid fungus infection (Batrachochytrium
      dendrobatidis). The mortalities occurred during December 1992 and between October
      and February in 1997-98 and December and February in 1998-99. Gross lesions
      varied from none to diffuse reddening of the skin of the abdomen, pelvic area,
      and legs. Microscopic lesions were characteristic of those previously reported
      for the disease and included diffuse epidermal hyperplasia, hyperkeratosis, and
      colonization of the keratinized layers of the epidermis by sporangia of the
      chytrid. Bacterial cultures did not yield a primary pathogenic agent. Virus
      isolation from frog tissues was negative. Batrachochytrium dendrobatidis was
      isolated from the skin of two of 10 R. yavapaiensis and one of two H. arenicolor
      cultured following necropsy. An additional nine of 11 clinically affected or dead
      R. yavapaiensis from the same locations, but not necropsied, were culture
      positive for B. dendrobatidis.

PMID- 11838219
TI  - Survey of South Polar skuas (Catharacta maccormicki) for blood parasites in the
      Vestfold Hills region of Antarctica.
AB  - Thin blood smears prepared from 125 South Polar skuas (Catharacta maccormicki) at
      breeding islands and feeding sites in the Vestfold Hills region of Antarctica
      between December 1999 and January 2000 did not contain hematozoa. These findings
      confirm results of previous smaller studies, and provide baseline data for this
      species.

PMID- 11838220
TI  - Safety of lyophilized SAG2 oral rabies vaccine in collared lemmings.
AB  - Fifteen collared lemmings (Dicrostonyx groenlandicus) were exposed to a
      lyophilized oral rabies vaccine designed to immunize wild carnivore populations.
      No animals contracted rabies from the vaccine as determined by the absence of
      clinical signs after 37 days and lack of rabies virus in brain tissue determined
      by the fluorescent antibody (FA) test. These results suggest that collared
      lemmings would not contract rabies if they ingested this lyophilized vaccine in
      the wild during bait vaccination programs for arctic foxes (Alopex lagopus).

PMID- 11838221
TI  - Aberrant Toxocara canis in a red fox.
AB  - During necropsy of a red fox (Vulpes vulpes) heart an adult, male Toxocara canis
      was found under the pericardium at the junction of the right ventricle and right
      atrium. The life cycle of T. canis is complex and includes tracheal and somatic
      migrations of larvae, and they can be found in many tissues throughout the host's
      body. However, it is rare for adult ascarids to be recovered outside of the small
      intestine. This is the first report of an adult T. canis inside the pericardial
      space.

PMID- 11838222
TI  - Esophageal diverticulum associated with Aerococcus viridans infection in a
      loggerhead sea turtle (Caretta caretta).
AB  - A juvenile loggerhead sea turtle (Caretta caretta) stranded in Gran Canaria,
      Spain was necropsied. The turtle was underweight, had sunken eyes, and small
      amounts of crude oil were in the oral cavity. The most significant lesion was a
      large esophageal diverticulum at the junction of the esophagus and stomach. The
      diverticulum was full of gas and green mucoid fluid and a diffuse thick yellow
      fibrinonecrotic membrane covered the mucosa. The lumen of the diverticulum also
      contained moderate numbers of cephalopods, crustaceans, and anthropogenic debris
      including crude oil balls, plastics, and fishing lines. Histologically there was
      a severe diffuse fibrinonecrotic esophagitis. Aerococcus viridans was isolated
      from the diverticulum. This is the first report of an esophageal diverticulum in
      a sea turtle. Although A. viridans is a known pathogen of lobsters and fishes,
      there are no reports of A. viridans infection in sea turtles.

PMID- 11838223
TI  - Bronchoscopy of cetaceans.
AB  - Bronchoscopy is a standard diagnostic and therapeutic procedure in respiratory
      medicine and has been performed on many animal species. Cetaceans suffer
      considerable morbidity and mortality from lower respiratory tract infections, and
      it is very difficult to sample lower respiratory tract secretions for
      microbiology and other analyses. We report our experience on performing
      fiberoptic bronchoscopy in three bottle-nosed dolphins (Tursiops truncatus) and
      one false killer whale (Pseudorca crassidens), which should help other clinicians
      in performing bronchoscopy in cetaceans.

PMID- 11838224
TI  - Notoedric and sarcoptic mange in free-ranging lynx from Switzerland.
AB  - Between March and December 1999, five free-ranging lynx (Lynx lynx) affected by
      mange were found dead or shot by game wardens in the Swiss Alps. In the first two
      cases, Notoedres cati was isolated from the skin; in the third and fourth case,
      Sarcoptes scabiei was the cause of the infection; and in the fifth case, a mixed
      infection was diagnosed. Red foxes (Vulpes vulpes) affected with sarcoptic mange
      and domestic cats infested with N. cati are likely to be the sources of
      infection. It seems improbable that mange will occur as an epidemic in lynx in
      Switzerland, but losses due to infections with N. cati and/or S. scabiei may have
      an impact on this small, geographically limited lynx population. This is the
      first report of notoedric mange in a free-ranging lynx and the first report of
      mange in lynx from Switzerland.

PMID- 11838225
TI  - Brucella abortus strain RB51 vaccination in elk. II. Failure of high dosage to
      prevent abortion.
AB  - Brucella abortus strain RB51 is used as a vaccine because it induces antibodies
      that do not react on standard serologic tests for brucellosis allowing
      differentiation between vaccination and infection. Strain RB51 was evaluated in
      captive elk (Cervus elaphus) to determine if vaccination protected against
      abortion following experimental challenge. Thirty elk were vaccinated
      intramuscularly with 1.0 x 10(10) colony-forming units (CFU) of strain RB51 in
      March 1998. Fourteen of these were given a booster dose of 1.13 x 10(10) CFU
      exactly 1 yr later. All vaccinated elk seroconverted via a modified dot blot
      assay to strain RB51 with the booster group having higher titers (P < or =
      0.001). Seventeen other elk served as unvaccinated controls. All elk were bred
      and determined pregnant using pregnancy-specific protein B analysis. Elk were
      challenged in March 2000 with 1.1 x 10(7) CFU of B. abortus strain 2308
      administered intraconjunctivally and all elk seroconverted to strain 2308.
      Fifteen of 17 control elk aborted; 16 of 16 elk given a single vaccination
      aborted (P = 0.44); and 13 of 14 elk given a booster aborted (P = 0.86). There
      were two viable calves in the control group and one in the booster group. Strain
      2308 was recovered from fetuses and nonviable calves in all groups. Based on the
      results of this and other studies, the use of strain RB51 to prevent abortion in
      elk cannot be recommended.

PMID- 11838226
TI  - A baiting system for delivery of an oral plague vaccine to black-tailed prairie
      dogs.
AB  - Laboratory and field studies were conducted between July and October 1999 to
      identify bait preference, biomarker efficacy, and bait acceptance rates for
      delivering an oral plague vaccine to black-tailed prairie dogs (Cynomys
      ludovicianus). Twenty juvenile captive prairie dogs were offered alfalfa baits
      containing either alfalfa, alfalfa and 5% molasses, or alfalfa, 5% molasses and
      4% salt. Based on the results of these trials we selected a bait containing
      alfalfa, 7% molasses, and 1% salt for field trials to determine bait acceptance
      rates by free-ranging animals. The biomarkers DuPont Blue dye, iophenoxic acid,
      and tetracycline hydrochloride were orally administered to captive prairie dogs
      to determine their efficacy. Only tetracycline proved effective as a biomarker.
      Two field trials were conducted at separate prairie dog colonies located at the
      Buffalo Gap National Grassland (Pennington County, South Dakota, USA). In Trial
      1, three baits containing tetracycline were distributed around each active burrow
      entrance and an additional bait was placed inside the burrow (1,276 baits total).
      In Trial 2, baits were distributed at the same density per burrow as Trial 1, but
      along transects spaced 10 m apart (1,744 baits total). Trapping began 3 days
      after bait distribution, and 30 prairie dogs then were captured at each site to
      determine the percentage of animals marked. In Trial 1, 67% of the prairie dogs
      captured had tetracycline deposits indicative of bait consumption. In Trial 2,
      83% of the prairie dogs had ingested a bait. Approximately 15% of the animals in
      both trials ate more than one bait. Fleas (Opisocrostis hirsutus) were found on
      64 of 70 (91%) of the prairie dogs captured during this study.

PMID- 11838228
TI  - Serologic evidence of infection with granulocytic ehrlichiae in black bears in
      Pennsylvania.
AB  - Serum samples from 381 black bears (Ursus americanus) killed in Pennsylvania
      (USA) on 24 November 1997 were analyzed for antibodies reactive to the agent of
      human granulocytic ehrlichiosis (HGE; Ehrlichia sp.) by indirect
      immunofluorescence assay. Antibody reactivity to HGE antigen was detected in 21%
      (81/381) of the samples collected. Reactive samples were reported from 56%
      (14/25) of the counties where bear samples were collected. Endpoint antibody
      titer ranged from 1:8 to 1:16, 192, with a geometric mean titer of 1:582. There
      was no significant difference in antibody prevalence between male and female
      bears (P < 0.01). However, adult bears were significantly more likely to have
      reactive antibodies than juvenile bears (P < 0.01). Attempts to amplify and
      detect granulocytic ehrlichial DNA from corresponding bear blood clots (n = 181)
      through nested polymerase chain reaction assays were unsuccessful. Further
      studies are needed for identification of the pathogen-responsible for induction
      of HGE-reactive. This is the first description of antibodies reactive to the HGE
      agent in black bears and suggests these mammals are infected with the agent of
      HGE or an antigenically related ehrlichial species.

PMID- 11838227
TI  - Prevalence of Bordetella avium infection in selected wild and domesticated birds
      in the eastern USA.
AB  - Bordetella avium is the etiologic agent of bordetellosis, a highly contagious
      upper respiratory disease of young poultry. Its prevalence among domesticated
      turkeys is well-known, but information on prevalence of this bacterium in other
      birds is limited. A survey of the prevalence of B. avium in wild and domesticated
      birds was conducted from June 1998 to January 2000, using tracheal cultures and
      serology. Of 237 blood samples from 61 species, 100 individuals from 41 species
      had antibodies against B. avium as determined with a microtiter agglutination
      test. Nine isolates of B. avium were cultured from 128 tracheal samples. Ribotype
      analysis of seven isolates from mallards (Anas platyrhynchos), one from a wild
      turkey (Meleagris gallopavo), and one from a Canada goose (Branta canadensis)
      indicated that they represent three strains, two of which were indistinguishable
      from clinical isolates from domesticated turkeys. Bordetella avium is present in
      wild bird populations of multiple species. Transmission from free-living avian
      populations to domesticated poultry populations may be possible and should be
      examined.

PMID- 11838229
TI  - Effect of short-term coyote removal on populations of coyote helminths.
AB  - Coyote (Canis latrans) removal programs often are initiated despite the potential
      population regulatory mechanism of parasitism with increased coyote density. We
      investigated the effect of intensive, short-term coyote removal on population
      levels of helminths in juvenile and adult coyotes from western Texas. Coyotes
      were killed by aerial gunning every 3 mo for 2 yr on two 5,000 ha areas, which
      reduced the overall coyote density of these areas by about 50%. Two other 5,000
      ha areas were used as comparison sites where a limited number of coyotes were
      killed each season. Densities on comparison sites remained stable throughout the
      study at a mean +/- 1 SE of 0.14 +/- 0.01 coyotes/km2. Twelve helminth species
      consisting of seven nematodes (Ancylostoma caninum, Physaloptera rara, Toxascaris
      leonina, Dirofilaria immitis, Spirocerca lupi, Oslerus osleri, and Capillaria
      aerophila), three cestodes (Taenia pisiformis, Taenia multiceps, and
      Mesocestoides sp.), one acanthocephalan (Oncicola canis), and one trematode
      (Alaria marcianae) were found in 252 coyotes. Of these, A. caninum, P. rara, T.
      multiceps, T. pisiformis, T. leonina, and S. lupi were common species. Rank
      transformed values for the mean abundances of A. caninum and T. multiceps and A.
      caninum, T. multiceps, and S. lupi were reduced in juvenile and adult coyotes,
      respectively, from the removal sites compared to respective helminth abundances
      in similar age class coyotes from comparison sites. Because A. caninum has been
      suggested as a population regulator of coyotes, a coyote removal program that
      results in a reduced density of coyotes and at the same time causes a reduced
      abundance of A. caninum, may in fact negate the regulatory effect that A. caninum
      has on coyote populations.

PMID- 11838230
TI  - Helminth community structure in an expanding white-winged dove (Zenaida asiatica
      asiatica) population.
AB  - Helminth communities of 171 fledged white-winged doves (Zenaida asiatica
      asiatica) from the expanding eastern population in Texas (USA) were examined from
      hosts collected 11 June to 19 September 1997 within their historical range, new
      breeding periphery, and an intermediate area. Eleven helminth species,
      representing 435 individuals, were found. Helminths occurred in three
      microhabitats, of which the small intestine was the most commonly occupied.
      Nematodes dominated numerically (76% of total worms), followed by cestodes (17%),
      and trematodes (7%). Infracommunities were species-poor; the most complex
      infracommunity consisted of three helminth species, which occurred in three host
      individuals, followed by two species that occurred in 13 hosts. The remaining 155
      doves had one (70) or no (85) species. The overall helminth component community
      was species-poor and was dominated by Ascaridia columbae which occurred in 26% of
      the white-winged doves and accounted for 65% of all helminth individuals.
      Prevalence and abundance of A. columbae varied by geographic region and host age,
      but not by host sex. Helminth component communities varied by geographic region,
      host age, and host sex. These differences were primarily attributable to unique
      occurrences of uncommon species within specific host subpopulations. Results
      suggest that the white-winged doves' multimodal regional abundance pattern,
      sympatry with other columbids, and granivorous diet may be more important in
      shaping helminth community structure than the influences often associated with
      geographic range expansion.

PMID- 11838232
TI  - Seroprevalence of Trypanosoma cruzi in raccoons from South Carolina and Georgia.
AB  - Trypanosoma cruzi, the causative agent of American trypanosomiasis or Chagas'
      disease, is of both medical and veterinary importance as is evidenced by chronic
      phase myocarditis in humans and dogs. Further, T. cruzi has been reported from
      over 20 species of wildlife reservoir hosts in the USA, with raccoons (Procyon
      lotor) and opossums (Didelphis virginiana) being the most common. Whereas
      previous studies on T. cruzi in raccoons have included only culture and direct
      examination of blood, the indirect immunofluorescent antibody test (IFAT) was
      used in the current study to detect anti-T. cruzi antibodies in the serum of
      raccoons. Of 221 raccoons trapped at 13 sites representing the five physiographic
      regions of South Carolina plus five sites in the Piedmont region of Georgia (from
      April 1997 to February 2000), 104 (47%) were seropositive. A higher
      seroprevalence in raccoons was observed in the coastal regions, with
      seroprevalence in the Lower Coastal Plain South (61%) being significantly higher
      than that in the Foothills (37%), Piedmont (42%), and Upper Coastal Plain (40%)
      regions. However, at a seroprevalence of 52%, the Lower Coastal Plain North was
      not significantly different from any other region. Although more female raccoons
      were infected than males, no statistical difference in prevalence was observed
      between sexes. The high seroprevalence of T. cruzi in raccoons, together with a
      few reports of wildlife isolates being infective for other wildlife species and
      domestic/laboratory animals, suggests that risk of T. cruzi infection may be
      higher than previously suspected.

PMID- 11838231
TI  - Diagnosis and seroprevalence of leptospirosis in California sea lions from
      coastal California.
AB  - The sensitivity and specificity of the microscopic agglutination test (MAT) as a
      method for detection of exposure to Leptospira spp. in California sea lions
      (Zalophus californianus) were determined. Sera came from individuals that
      demonstrated clinical signs of renal disease, had lesions suggestive of
      leptospirosis at necropsy, and had visible leptospires in silver stained kidney
      sections as positive controls. Sera from unexposed captive individuals were used
      as negative controls. The test was 100% sensitive at 1:3,200 for confirming renal
      infection and 100% specific at negative < 1:100 for detection of Leptospira
      interrogans scrovar pomona antibodies by MAT in California sea lions. Leptospira
      interrogans serovar pomona was used as a screening serovar because it has been
      isolated previously from the kidneys and placentas of California sea lions, and
      there appears to be cross-reactivity between serovar pomona and other serovars.
      Sera from 225 free-ranging California sea lions presented to one of three
      participating California (USA) coastal marine mammal rehabilitation centers in
      1996 were then evaluated for antibodies to serovar pomona using the MAT. The
      overall seroprevalence was 38.2% (86/225), although the prevalence varied among
      locations from 100% (38/38) in animals at the Marine Mammal Care Center (Fort
      MacArthur, California, USA) to 0% (0/14) at SeaWorld California (San Diego,
      California). At The Marine Mammal Center (Sausalito, California) [prevalence
      27.8% (48/173)], the majority of seropositive animals were subadults and adults,
      and males were 4.7 times more likely to be seropositive to serovar pomona than
      females. When combining results from all three centers, subadult and adult
      animals were more likely to be seropositive than pups and juvenile sea lions, and
      the highest proportion of seropositive animals presented during the autumn
      months. Serum elevations of blood urea nitrogen, creatinine, phosphorus, and/or
      calcium were associated with seropositivity to serovar pomona. We found no
      association between potassium or sodium levels and seropositivity.

PMID- 11838233
TI  - Causes of mortality in reintroduced Eurasian lynx in Switzerland.
AB  - Seventy-two lynx, found dead in the Swiss Alps and the Jura Mountains
      (Switzerland) from 1987-99, were evaluated to determine the cause of death.
      Seventy-two per cent (52/72) of all animals died because of noninfectious
      diseases or causes such as vehicular collision and poaching. Eighteen percent
      (13/72) died from infectious diseases, including some which could have been
      transferred to the lynx from domestic animals or other wild animals such as
      panleukopenia and sarcoptic mange. If only radio-tagged animals (included in a
      monitoring program) were taken into consideration, the percentage of mortality
      caused by infectious diseases rose to 40%, indicating that infections might be
      underestimated in randomly found mortality events. We hypothesize that even a few
      cases of infections in a small population like the lynx, which are additionally
      threatened by noninfectious causes, may threaten the long term survival of the
      population.

PMID- 11838234
TI  - Viral and bacterial serology of free-ranging Pacific walrus.
AB  - Serum or heparinized plasma samples were obtained between 1994 and 1996 from 20
      male and 20 female adult free-ranging Pacific walrus (Odobenus rosmarus
      divergens) from St. Lawrence Island and Round Island, Alaska. Samples were
      screened for antibodies to some potentially pathogenic bacteria and viruses. No
      sample had detectable antibody to Brucella spp. Three of 40 (8%) had low antibody
      titers to Leptospira interrogans serovars. Phocine distemper virus antibodies
      were not detected. Serologic responses to one or more caliciviruses (San Miguel
      sea lion virus 12 or vesicular exanthema of swine serotypes E54, F55, G55, 1934B)
      were detected in 18% (seven of 40) walrus. Antibodies to one or more subtypes of
      influenza A virus (H10, N2, N3, N5, N6, N7) were detected in 21% (eight of 38).
      Periodic screening of free-ranging populations for exposure to infectious
      diseases has become an important component of bio-monitoring programs to
      facilitate understanding and detecting trends in marine mammal populations.

PMID- 11838235
TI  - Role of DNA sequence in nucleosome stability and dynamics.

PMID- 11838236
TI  - Emerging issues of connexin channels: biophysics fills the gap.
AB  - This summary is a proposed synthesis of available information for the non
      specialist. It does not incorporate all the published data, is inconsistent with
      some, and reflects the biases of the author. Connexin proteins have a common
      transmembrane topology, with four alpha-helical transmembrane domains, two
      extracellular loops, a cytoplasmic loop, and cytoplasmic N- and C-terminal
      domains. The sequences are most conserved in the transmembrane and extracellular
      domains, yet many of the key functional differences between connexins are
      determined by amino-acid differences in these largely conserved domains. Each
      extracellular loop contains three cysteines with invariant spacing (save one
      isoform) that are required for channel function. The junctional channel is
      composed of two end-to-end hemichannels, each of which is a hexamer of connexin
      subunits. Hemichannels formed by some connexin isoforms can function as well
      behaved, single-membrane-spanning channels in plasma membrane. In junctional
      channels, the cysteines in the extracellular loops form intra-monomer disulfide
      bonds between the two loops, not intermonomer or inter-hemichannel bonds. The end
      to-end homophilic binding between hemichannels is via non-covalent interactions.
      Mutagenesis studies suggest that the docking region contains beta structures, and
      may resemble to some degree the beta-barrel structure of porin channels. The two
      hemichannels that compose a junctional channel are rotationally staggered by
      approximately 30 degrees relative to each other so that the alpha-helices of each
      connexin monomer are axially aligned with the alpha-helices of two adjacent
      monomers in the apposed hemichannel. At present there is a published 3D map with
      7.5 A resolution in the plane of the membrane, based on electron cryomicroscopy
      of 2D crystals of junctional channels formed by C-terminal truncated Cx43. The
      correspondence between the imaged transmembrane alpha-helices and the known
      transmembrane amino-acid sequences is a matter of debate. Each of the
      approximately 20 connexin isoforms produces channels with distinct unitary
      conductances, molecular permeabilities, and electrical and chemical gating
      sensitivities. The channels can be heteromeric, and subfamilies among connexins
      largely determine heteromeric specificity, similar to the specificities within
      the voltage-dependent potassium channel superfamily. The second extracellular
      loop contains the primary determinants of the specificity of hemichannel
      hemichannel docking (analogous to the tetramerization domain of potassium
      channels). The 7.5 A map shows that each monomer exposes only two transmembrane
      alpha-helices to the pore lumen. However the conductance state of the imaged
      structure and the effects of the C-terminal truncation are unknown, so it is
      possible that other transmembrane domains contribute to the lumen in other
      functional states of the channel. In the transmembrane region, SCAM and
      mutagenesis data suggest that parts of the first three transmembrane alpha
      helices are exposed to the lumen. Some of these data are contradictory, but may
      reflect conformational or isoform differences. There is reason to think that the
      first part of the N-terminal cytoplasmic domain can line the pore in some
      conformations. In the extracellular part of junctional channels, the N-terminal
      portion of the first extracellular loop is exposed to the lumen. The unitary
      conductances through connexin channels vary over an order of magnitude, from 15
      pS to over 300 pS. There is a range of charge selectivities among atomic ions,
      from slightly anion selective to highly cation selective, which does not
      correlate with unitary conductance. There appear to be substantial ion-ion
      interactions within the pore, making the GHK model of assessing selectivities of
      limited value. Pores formed by different connexins have a range of limiting
      diameters as assessed by uncharged and charged probes, which also does not
      correlate with unitary conductance (i.e. some have high conductance but have a
      narrow limiting diameter, and vice versa). Channels formed by different connexins
      have different permeabilities to various cytoplasmic molecules. Where it has been
      assessed, the selectivity among cytoplasmic molecules is substantial and does not
      correlate in an obvious manner with the size selectivity data derived from
      fluorescent tracer studies, suggesting there are chemical specificities within
      the pore that enhance or reduce permeability to specific cytoplasmic molecules,
      functionally analogous to the ability of some porins to facilitate transport of
      specific substrates. For example, heteromeric channels with different
      stoichiometries or arrangements of isoforms can distinguish among second
      messengers. The differences in permeability to cytoplasmic molecules have
      biological consequences; in most cases one connexin cannot fully substitute for
      another. Voltage and chemical gating mechanisms largely operate within each
      hemichannel, though there is evidence for inter-hemichannel allosteric effects as
      well. There are at least two distinct gating mechanisms. One (Vj-gating) is a
      voltage-driven mechanism that governs rapid transitions between conducting
      states. Its voltage sensor involves charges in the first several positions of the
      cytoplasmic N-terminal domain and possibly in the N-terminal part of the first
      extracellular loop, which may both be exposed to the lumen of the pore in some
      states. The polarity of Vj-gating sensitivity is connexin-specific, closing with
      depolarization for some connexins and with hyperpolarization for others. The
      polarity can be reversed by point mutations at the second position. The lower
      conductance states induced by Vj-gating correspond to physical restrictions of
      the pore, and thus restricted or eliminated molecular permeation. Since the
      channels are not fully closed by Vj-gating, it can be seen as a way to eliminate
      molecular signaling while leaving electrical signaling operational. A second,
      independent gating mechanism mediates slow transitions (approximately 10-30 ms)
      into and out of non-conducting state(s). These transitions can occur in response
      to voltage ('loop gating'), chemical factors such as pH and lipophiles ('chemical
      gating'), and the docking of two hemichannels (sometimes called the 'docking
      gate'). These slow transitions may reflect a common structural change induced by
      these several effectors (electrical, chemical and homodimerization).
      Alternatively, they could reflect distinct gating processes responding to one or
      more of these effectors, that are indistinguishable at the single-channel level
      and have yet to be resolved mechanistically. The slow or loop gate closes with
      hyperpolarization. As a result, where Vj-gating closes with depolarization,
      individual hemichannels can close in response to both polarities of voltage (but
      only to a subconductance state for the Vj-gating polarity). Because of this, it
      is difficult to assign a macroscopic voltage sensitivity, or its modification due
      to mutagenesis, chemical modification or heteromeric interactions, to one or the
      other of these very distinct voltage-sensitive processes. This distinction can be
      made reliably only at the single-channel level. The Vj-gating voltage sensor and
      the loop-gating voltage sensor appear to be independent structures, since the Vj
      gating voltage sensitivity can modified without effect on loop gating. For some
      connexins, certain modifications of the C-terminal domain seem to interfere with
      the operation of the Vj-gate while leaving loop gating unaffected. In some
      connexins, but not all, the chemical sensitivity to pH can involve interactions
      between regions of the C-terminal domain and cytoplasmic loop. Whether these
      regions exert their effects directly by physically blocking the pore, or by
      allosteric mechanisms (which may be more consistent with the relatively long time
      course of closure) is not clear. For several connexins, truncation of the C
      terminal domain eliminates the pH sensitivity, and co-expressing the domain with
      the truncated connexin restores the pH sensitivity. This has a functional
      resemblance to the particle-receptor mechanism for N-type inactivation of Shaker
      channels. What is being protonated is not clear, and may involve cytoplasmic
      factors, such as endogenous aminosulfonates. For other connexins, the action of
      pH does not involve the C-terminal domain and seems due to direct protonation of
      connexin. PKC phosphorylation of serine(s) in the C-terminal domain can affect
      the substate occupancy of at least one connexin. Phosphorylation of series in the
      C-terminal domain by MAP kinase appears to facilitate an interaction between it
      and an unknown receptor domain to eliminate coupling. This process has yet to be
      studied at the single-channel level. It also has a functional analogy to the
      particle-receptor model of channel inactivation. Both MAP kinase phosphorylation
      induced and pH-induced inhibition can be mediated in truncated connexins by the
      corresponding free peptide. However, the relation between these two mechanisms
      are unexplored, as are specific mechanisms of direct endogenous regulation of
      connexin channel activity. (ABSTRACT TRUNCATED)

PMID- 11838237
TI  - The aperture problem for visual motion and its solution in primate cortex.
AB  - A primary function of the visual system is to analyze the trajectories of moving
      objects. This seemingly simple process is complicated by theoretical
      considerations, which show that measurements of the velocity of a moving object
      are inevitably confounded with the spatial arrangement of its edges. This type of
      confusion is likely to be detrimental to an organism's survival, and so must be
      resolved. This review describes some recent experiments that demonstrate the
      existence and time-course of a solution in the visual cortex of the macaque
      brain. Related work on perception, behavior, and computational theory is
      discussed.

PMID- 11838238
TI  - Direct imaging of single-molecules: from dynamics of a single DNA chain to the
      study of complex DNA-protein interactions.
AB  - Recent years have seen significant advances in the characterization and
      manipulation of individual molecules. The combination of single-molecule
      fluorescence and micromanipulation enables one to study physical and biological
      systems at new length scales, to unravel qualitative mechanisms, and to measure
      kinetic parameters that cannot be addressed by traditional biochemistry. DNA is
      one of the most studied biomolecules. Imaging single DNA molecules eliminates
      important limitations of classical techniques and provides a new method for
      testing polymer dynamics and DNA-protein interactions. Here we review some
      applications of this new approach to physical and biological problems, focusing
      on videomicroscopy observations of individual DNA chains extended in a shear
      flow. We will first describe data obtained on the stretching, relaxation and
      dynamics of a single tethered polymer in a shear flow, to demonstrate that the
      deformation of sheared tethered chains is partially governed by the thermally
      driven fluctuations of the chain transverse to the flow direction. Next, we will
      show how single-molecule videomicroscopy can be used to study in real time DNA
      folding into chromatin, a complex association of DNA and proteins responsible for
      the packaging of DNA in the nucleus of an eukaryotic cell.

PMID- 11838240
TI  - Hydrogenation properties of supported nanosized gold particles.

PMID- 11838239
TI  - Three-dimensional reconstruction of single particle electron microscopy: the
      voltage sensitive sodium channel structure.
AB  - Single particle analysis in electron microscopy allows direct observation of the
      reconstructed three-dimensional structures of protein molecules. This method
      enables a more comprehensive study of membrane proteins which have been
      problematic in structural studies using X-ray crystallography. These membrane
      proteins include the voltage-sensitive ion channel proteins, which play an
      important rule in neural activities, and have great medical significance. The
      method described is supported by the development of cryo-electron microscopy and
      the angular reconstitution method. This review summarizes certain principles
      governing single particle analysis employing angular reconstitution. This method
      was applied to our study of the voltage-sensitive sodium channel, and the results
      are discussed. With improvements in resolutions and statistical analyses, the
      single particle technique is considered to be advantageous in studies of the
      structural changes and molecular interactions of protein molecules.

PMID- 11838241
TI  - Oceanic slab melting and mantle metasomatism.
AB  - Modern plate tectonic brings down oceanic crust along subduction zones where it
      either dehydrates or melts. Those hydrous fluids or melts migrate into the
      overlying mantle wedge trigerring its melting which produces arc magmas and thus
      additional continental crust. Nowadays, melting seems to be restricted to cases
      of young (< 50 Ma) subducted plates. Slab melts are silicic and strongly sodic
      (trondhjemitic). They are produced at low temperatures (< 1000 degrees C) and
      under water excess conditions. Their interaction with mantle peridotite produces
      hydrous metasomatic phases such as amphibole and phlogopite that can be more or
      less sodium rich. Upon interaction the slab melt becomes less silicic (dacitic to
      andesitic), and Mg, Ni and Cr richer. Virtually all exposed slab melts display
      geochemical evidence of ingestion of mantle material. Modern slab melts are thus
      unlike Archean Trondhjemite-Tonalite-Granodiorite rocks (TTG), which suggests
      that both types of magmas were generated via different petrogenetic pathways
      which may imply an Archean tectonic model of crust production different from that
      of the present-day, subduction-related, one.

PMID- 11838242
TI  - Time-frequency analysis of surface myoelectric signals during athletic movement.

PMID- 11838243
TI  - Providing appropriate exercise levels for the elderly.

PMID- 11838244
TI  - Analyzing dynamic EMG and VMG signals of respiratory muscles.

PMID- 11838245
TI  - EMG-based measures of fatigue during a repetitive squat exercise.

PMID- 11838247
TI  - Compression of color skin tumor images with vector quantization.

PMID- 11838246
TI  - Heterogeneous integration through electrokinetic migration.

PMID- 11838248
TI  - Antenatal fetal risk assessment using a neurofuzzy technique.

PMID- 11838249
TI  - Analyzing blood cell concentration as a stochastic process.

PMID- 11838250
TI  - Determining flexor-tendon repair techniques via soft computing.
AB  - An SC-based multi-objective decision-making method for determining the optimal
      flexor-tendon repair technique from experimental and clinical survey data, and
      with variable circumstances, was presented. Results were compared with those from
      the Taguchi method. Using the Taguchi method results in the need to perform ad
      hoc decisions when the outcomes for individual objectives are contradictory to a
      particular preference or circumstance, whereas the SC-based multi-objective
      technique provides a rigorous straightforward computational process in which
      changing preferences and importance of differing objectives are easily
      accommodated. Also, adding more objectives is straightforward and easily
      accomplished. The use of fuzzy-set representations of information categories
      provides insight into their performance throughout the range of their universe of
      discourse. The ability of the technique to provide a "best" medical decision
      given a particular physician, hospital, patient, situation, and other criteria
      was also demonstrated.

PMID- 11838251
TI  - Of big bangs and small fizzes.

PMID- 11838252
TI  - Recent advancements in the analysis of dynamic EMG data.

PMID- 11838253
TI  - Muscle activation intervals and EMG envelope in clinical gait analysis.

PMID- 11838254
TI  - Dynamic EMG: a clinician's perspective.

PMID- 11838255
TI  - A tool for assessing rehabilitation and workplace factors.

PMID- 11838256
TI  - From static to dynamic contractions.

PMID- 11838257
TI  - Improving detection of muscle activation intervals.

PMID- 11838258
TI  - Estimation and application of EMG amplitude during dynamic contractions.
AB  - The sections above have described an EMG amplitude estimator and an initial
      application of this estimator to the EMG-torque problem. The amplitude estimator
      consists of six stages. In the first stage, motion artifact and power-line
      interference are attenuated. Motion artifact is typically removed with a highpass
      filter. Elimination of power-line noise is more difficult. Commercial systems
      tend to use notch filters, accepting the concomitant loss of "true" signal power
      in exchange for simplicity and robustness. Adaptive methods may be preferable,
      however, to preserve more "true" signal power. In stage two, the signal is
      whitened. One fixed whitening technique and two adaptive whitening methods were
      described. For low-amplitude levels, the adaptive whitening technique that
      includes adaptive noise cancellation may be necessary. In stage three, multiple
      EMG channels (all overlying the same muscle) are combined. For most applications,
      simple gain normalization is all that is required. Stage four rectifies the
      signal and then applies the power law required to demodulate the signal. In stage
      six, the inverse of the power law is applied to relinearize the signal. Direct
      comparison of MAV (first power) to RMS (second power) processing demonstrates
      little difference between the two. Therefore, unless there is reason to believe
      that the EMG density departs strongly from that found in the existing studies,
      RMS and MAV processing are essentially identical. In stage five, the demodulated
      samples are averaged across all channels and then smoothed (time averaged) to
      reduce the variance of the amplitude estimate, but at the expense of increasing
      the bias. For best performance, the window length that best trades off variance
      and bias error is selected. The advanced EMG processing was next applied to
      dynamic EMG-torque estimation about the elbow joint. Results showed that improved
      EMG amplitude estimates led to improved EMG-torque estimates. An initial
      comparison of different system-identification techniques and model orders was
      reported. It is expected that these advanced processing and identification
      algorithms will also improve performance in other EMG applications, including
      myoelectrically controlled prostheses, biofeedback, and ergonomic assessment.

PMID- 11838259
TI  - Extraction of the envelope from surface EMG signals.

PMID- 11838260
TI  - Effect of joint angle on EMG variables in leg and thigh muscles.

PMID- 11838261
TI  - Generalizability of trunk muscle EMG and spinal forces.
AB  - The generalizability of trunk muscle EMG and spinal loading estimates obtained
      from an EMG-assisted biomechanical model was assessed over three occasions and
      three repetitions. The greatest sources of variability consisted of the
      intersubject differences and the interaction between subject and occasion. The ID
      (reliability coefficient) was less for trunk muscle activity compared with
      estimates of anteroposterior shear force, compression force, and gain computed
      from the biomechanical model. In order to obtain an ID of 0.8, we recommend five
      testing occasions for submaximal EMG measurements and three testing occasions for
      biomechanical estimates. Reproducible estimates of maximal trunk extensor EMG
      could not be obtained within five testing occasions and five repetitions.
      Although many recruitment patterns could cause the same extension torque output,
      their net effect on internal loading seems to be less variable than the
      underlying measurements.

PMID- 11838262
TI  - Influences of dynamic factors on myoelectric parameters.

PMID- 11838263
TI  - Assessing fatigue with electromyographic spike parameters.

PMID- 11838264
TI  - Analyzing surface myoelectric signals recorded during isokinetic contractions.

PMID- 11838266
TI  - Remembering Norman L. Cannon, M.D.

PMID- 11838265
TI  - Home delivery of palivizumab: outcomes and compliance in regional preterm
      infants.
AB  - Palivizumab, a monoclonal antibody against respiratory syncytial virus (RSV), has
      been shown to be effective in preventing RSV-related hospitalization in preterm
      infants; however, ensuring infants receive the desired monthly injections remains
      a challenge. We studied two cohorts of preterm infants and the rate of documented
      RSV illness in infants receiving palivizumab at home between 1998 and 2000.
      Medical records were reviewed for the number of doses received, hospitalization
      for RSV illness, and other demographic data. Parents in Cohort 1, 1998-1999, were
      prospectively surveyed to determine satisfaction with delivery of palivizumab. In
      Cohort 1, the home group (n = 32) received 89 +/- 19 percent of their scheduled
      course as compared to 66 +/- 32 percent in the office group (n = 41, p < .01),
      with 67 percent in the home group receiving their entire scheduled course as
      compared to 36 percent in the office group (p = .02). Of the parents surveyed, 70
      percent in the home group indicated that they were satisfied with the way
      palivizumab was administered as compared to 76 percent in the office group (p =
      .44). In Cohort 2, 1999-2000, 175 infants received palivizumab at home, and 161
      of these (92 percent) completed therapy as ordered. None of the infants had a
      documented infection with RSV. In our population infants receiving palivizumab at
      home were more likely to receive their entire scheduled course and less likely to
      miss doses than infants receiving palivizumab in an office setting. The high rate
      of compliance with home delivery is associated with a low rate of documented
      severe RSV illness.

PMID- 11838268
TI  - Cholesterol-lowering properties and safety of chitosan.
AB  - Chitosan (CAS 9012-76-4) is derived by alkaline deacetylation from chitin, an
      abundant polymeric product of natural biosynthesis especially in crustaceans. It
      is available in a primary, unorganised structure, but also in a microcrystalline
      form. As a dietary supplement, chitosan has been claimed to control obesity and
      to lower serum cholesterol. A variety of chitosan products have been freely
      available worldwide in health stores and pharmacies. This review summarises the
      current knowledge about cholesterol-lowering and safety properties of chitosan
      and focuses its possible application for the treatment of hypercholesterolaemia.
      Chitosan behaves as a polycationic(+) cellulose-like fibrillar biopolymer that
      forms films with negatively charged surfaces. It is not specifically hydrolysed
      by digestive enzymes in man, but limited digestion of chitosan due to bacterial
      flora and to the unspecific enzymes might occur. Negatively charged molecules in
      stomach attach strongly to the positive charged tertiary amino group (-NH3+) of
      chitosan. Therefore, chitosan reduces fat absorption from gastrointestinal tract
      by binding with anionic carboxyl groups of fatty and bile acids, and it
      interferes with emulsification of neutral lipids (i.e., cholesterol, other
      sterols) by binding them with hydrophobic bonds. In short-term animal studies the
      safety of chitosan has been good. There are only few studies with chitosan in
      humans. In man, dietary chitosan has been reported to reduce serum total
      cholesterol levels by 5.8-42.6% and low-density lipoprotein levels by 15.1-35.1%.
      In short-term trials up to 12 weeks, no clinically significant symptoms have been
      observed with chitosan compared to placebo. Mild and transitory nausea and
      constipation have been reported in 2.6-5.4% of subjects. Although chitosan has
      been clinically well tolerated, it cannot be recommended to people allergic to
      crustaceans.

PMID- 11838269
TI  - General pharmacological profile of the novel muscarinic receptor agonist SNI
      2011, a drug for xerostomia in Sjogren's syndrome. 1st communication: effects on
      general behavior and central nervous system.
AB  - A novel muscarinic receptor agonist, SNI-2011 ((+/-)-cis-2-methylspiro[1,3
      oxathiolane-5,3'-quinuclidine] monohydrochloride hemihydrate, cevimeline, CAS
      153504-70-2), is a candidate therapeutic drug for xerostomia in Sjogren's
      syndrome. The general pharmacological properties of this drug on general behavior
      and the central nervous system were investigated in mice, rats and cats. 1.
      General behavior: When SNI-2011 was administered orally to mice at 100 mg/kg,
      mydriasis, a decrease of spontaneous motor activity, tremor, convulsions,
      salivation, abnormal posture, abnormal gait, reduced grip strength and reduced
      response against external stimulating were observed, and 2 out of 6 animals died.
      At 10 mg/kg or lower, no particular sign was observed except mydriasis, which
      appeared to be caused via the peripheral muscarinic acetylcholine receptors. 2.
      Central nervous system: SNI-2011 had no effect on the motor coordination in mice.
      Hypothermia was observed in rats and reduced spontaneous motor activity,
      analgesia and enhanced maximum electroshock-induced convulsions were observed in
      mice after oral administration of 30 mg/kg SNI-2011. Slight increase in the rate
      of theta-wave band in the hippocampal EEG of rats and spinal multisynaptic
      reflexes in cats were observed after intravenous injection of 10 mg/kg SNI-2011.
      At an oral dose of 10 mg/kg, prolongation of thiopental-induced sleeping time in
      mice was observed. The prolongation of sleeping time was inhibited by a
      peripheral muscarinic antagonist. These results suggest that SNI-2011 has
      muscarinic effects on general behavior and the central nervous system at the
      doses approximately 10-fold higher than the effective doses needed for saliva
      secretion.

PMID- 11838270
TI  - Synthesis and calcium channel antagonist activity of new 1,4-dihydropyridine
      derivatives containing dichloroimidazolyl substituents.
AB  - A group of dialkyl, dicycloalkyl and diaryl ester analogues of nifedipine (CAS
      21829-25-4), in which the ortho-nitrophenyl group at position 4 is replaced by a
      4,5-dichloroimidazolyl 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 in alkyl
      esters series showed that increasing the length of the methylene chain in C3 and
      C5 ester substituents (from n = 0 to n = 2) increased the activity. When
      increasing of the length was accompanied by increase of the hindrance, the
      activity decreased. In the unsymmetrical diester series, the results showed when
      R1 is a small substituent (R1 = Me), increasing of the lipophilic property in R2
      substituent increases the activity if this high lipophilicity is not accompanied
      by steric hindrance. The results demonstrate that in the unsymmetrical series,
      several compounds (benzyl methyl, benzyl isopropyl and cyclohexyl ethyl) had
      activity similar to that of the reference drug nifedipine. In symmetrical
      diesters compounds, the most active compound was the diphenethyl ester derivative
      being more active than nifedipine. These structure-activity data indicate that
      the 4-(4,5-dichloroimidazolyl) moiety is the bioisoester of 3-nitrophenyl and 2,3
      dichlorophenyl moieties.

PMID- 11838271
TI  - Synthesis, enantioseparation and pharmacological activity of 4-aryl-7,7-dimethyl
      5-oxo-1,2,3,4,5,6,7,8-octahydroquinazoline-2-thiones.
AB  - 4-Aryl-7,7-dimethyl-5-oxo-1,2,3,4,5,6,7,8-octahydroquinazoline-2-thione
      derivatives (1-8) have been prepared by modified Biginelli reaction from 5,5
      dimethyl-1,3-cyclohexanedione, the aromatic aldehydes and thiourea. The
      structures of the compounds were confirmed by spectroscopic and elemental
      analysis. Racemic compounds were resolved into their enantiomers by HPLC using an
      amylose tris-(3,5-dimethylphenylcarbamate) chiral stationary phase in the normal
      phase mode. The calcium antagonist activities of the compounds were determined by
      the tests performed on isolated rat ileum and lamb carotid artery. Compounds 2,
      3, 4 and 6 were the most active compounds on isolated rat ileum. Compounds 2 and
      3 were significantly active on lamb carotid artery.

PMID- 11838273
TI  - Synthesis of some new diaryl and triaryl hydrazone derivatives as possible
      estrogen receptor modulators.
AB  - 1,2-Bis(4-substituted phenyl)-2-methyl ethanone (2,4-dinitrophenyl)hydrazones and
      1-naphthyl-1-(4-substituted phenyl)-methanone (2,4-dinitrophenyl)hydrazones have
      been synthesized and evaluated for their anti-implantation, uterotrophic,
      antiuterotrophic, anticancer and antimicrobial activities. Diphenolic hydrazone
      (compound 6) showed maximum uterotrophic inhibition of 70%, whereas compound 20
      exhibited cytotoxicity in the range of 50-70% against MCF-7 and ZR-75-1 human
      malignant breast cell lines.

PMID- 11838272
TI  - Effect of troglitazone on endothelial function in type 2 diabetic patients.
AB  - Lysophosphatidylcholine (lysoPC), a component of oxidized low-density lipoprotein
      cholesterol (LDL-C), has been reported to impair nitric oxide production and
      endothelium-dependent vasorelaxation. The effects of troglitazone (CAS 97322-87
      7), which is an antidiabetic agent with antioxidant properties, on serum levels
      of lysoPC and nitrite/nitrate (NOx) have been studied. Eight patients with Type 2
      diabetes (non-insulin dependent diabetes mellitus, NIDDM) were studied (age: 61.5
      +/- 2.8 years; diabetes duration: 10.2 +/- 1.6 years). They were additionally
      given troglitazone (200 mg once daily) since their fasting plasma glucose (FPG)
      and HbA1c levels had been increased in spite of conventional medications. Before
      and after 12 weeks of treatment with troglitazone their blood pressure, FPG,
      HbA1c, lipid profiles and NOx were measured. Troglitazone treatment had a slight
      depressor effect (decreasing the blood pressure from 133 +/- 5/72 +/- 3 to 127 +/
      4/68 +/- 1 mmHg; p < 0.05). FPG and HbA1c were significantly decreased with the
      therapy (181 +/- 10 to 160 +/- 10 mg/dl; p < 0.05 and 9.1 +/- 0.6 to 8.1 +/-
      0.5%; p < 0.05, respectively). In contrast, total cholesterol, triglyceride, high
      density lipoprotein cholesterol, and LDL-C were maintained within normal limits
      throughout the study. Although lysoPC and NOx levels were not altered, a negative
      correlation between lysoPC and NOx levels was observed. These results suggest
      that troglitazone is a beneficial agent improving FPG and HbA1c levels in NIDDM
      patients, while its effects on serum lysoPC and NOx levels, at least for 12
      weeks, seem to be minimal.

PMID- 11838274
TI  - Effects on Mycobacterium avium replication in normal human macrophages by
      deferiprone (L1) and other iron chelators. Possible implications on toxicity.
AB  - Mycobacterium avium growth in cultured human macrophages is influenced by serum
      lipids, transferrin and iron levels. Iron-saturated transferrin enhances M. avium
      growth, whereas apotransferrin inhibits mycobacterial replication. The ability of
      iron chelators to mimic the effects of transferrin on intracellular and
      extracellular M. avium growth was examined. Smooth, transparent, AIDS patient
      derived M. avium 7497 scrovar 4 was used to infect 7-day cultured human
      macrophages. Growth was measured by determining the colony-forming units (CFU)
      after infected macrophages were lysed 0 to 7 days after infection. The new iron
      chelating drug deferiprone (1,2-dimethyl-3-hydroxypyrid-4-one or L1, CAS 30652-11
      0), 1-ethyl-2-methyl-3-hydroxypyrid-4-one (L1NEt), 1-propyl-2-methyl-3
      hydroxypyrid-4-one (L1NPr), 1-allyl-2-methyl-3-hyproxypyrid-4-one (L1NAll), and
      3,4-dihydroxycinnamic acid enhanced intracellular and extracellular mycobacterial
      replication at concentrations of 0.1-2.5 micrograms/ml. 2-Pyridinecarboxaldehyde
      2-quinolylhydrazone (PCQH) inhibited intracellular replication from 0.1-1.0
      microgram/ml. Most, but not all of the PCQH-induced intracellular inhibition
      could be eliminated using iron at concentrations greater than 1.0 microgram/ml.
      Iron also suppressed the effects of PCQH on extracellular M. avium replication.
      These results indicate that iron chelators may have variable effects at different
      concentrations and can significantly alter both intracellular and extracellular
      M. avium replication. It is suggested that at low concentrations deferiprone and
      other aketohydroxypyridine chelators could enhance the growth of M. avium but at
      high concentrations may function as adjunct therapy with other antimicrobials
      against infections with M. avium. These findings are important for therapeutic
      considerations and dose protocol design in relation to the new iron chelating
      drug deferiprone, which is currently used in thalassaemia and other iron loaded
      patients, some of whom are suffering from AIDS.

PMID- 11838275
TI  - Lekteplase--a secreted tissue plasminogen activator derivative from Escherichia
      coli.
AB  - Fermentation studies of batch-mode cultivation in 4-L fermenters were carried out
      to obtain an active recombinant DNA-derived tissue plasminogen activator (t-PA)
      deletion mutant, lekteplase, secreted and correctly folded from Escherichia coli.
      The OmpA signal sequence was used to deliver the heterologous product composed of
      kringle 2 plus serine protease domain (K2S) to the medium. Supplementing the
      complex medium with 10% glycerol and 20 mmol/l magnesium chloride led to an
      increase in cell numbers with final cell density reaching an OD600 of 24. The
      expression level of lekteplase in the medium detected by sandwich ELISA was 100
      mg/L. Enzymatic activity of lysine-sepharose purified product was demonstrated by
      amidolytic assay, in vitro fibrin clot lysis, and copolymerization PAGE.

PMID- 11838276
TI  - Detection of isolated mistletoe lectin chains in plant extracts.
AB  - New test systems which allow to detect with high sensitivity the presence of
      isolated subunits in mistletoe extracts subunits are proposed. Interaction of
      monoclonal antibodies MNA5 and mouse anti-MLA (mistletoe lectin I A-chain) immune
      serum with panel of synthetic octapeptides linked to the surface of polyethylene
      pins have been analyzed. Two main immunogenic epitopes in MLA, AETHL and DGVFNNP,
      were found. The second sequence can be part of the MNA5 antibody epitope as shown
      by antigenic prediction. Possible role of the isolated A- and B-chains of
      mistletoe lectins in pharmacological effects of plant extracts is discussed.

PMID- 11838277
TI  - Microbiological and pharmaco-toxicological profile of nifuratel and its
      favourable risk/benefit ratio for the treatment of vulvo-vaginal infections. A
      review.
AB  - Nifuratel (CAS 4936-47-4) is a furane-derivative provided with a strong
      trichomonicidal activity equivalent to that of metronidazole (CAS 443-48-1); it
      has a broad antibacterial spectrum of action, including both Gram-negative and
      Gram-positive organisms. It is active against Chlamydia trachomatis and
      Mycoplasma spp. and has also some degree of activity against Candida spp. and
      mycetes. Its broad spectrum of action, confirmed by in vitro and in vivo studies,
      covers virtually all the micro-organisms responsible for the infections of the
      genito-urinary tract. Nifuratel has a very safe toxicological profile. It is
      practically non-toxic in acute tests in mice and rats and is also well tolerated
      after repeated oral and intravaginal administrations. Nifuratel is devoid of
      teratogenic effects. The comparison among past and recent clinical studies
      confirms that, in contrast to metronidazole, no resistance phenomena to the
      treatment with nifuratel are reported. The drug can be used during pregnancy due
      to the absence of teratogenic effects. In conclusion, nifuratel shows a very
      favourable risk/benefit ratio for the treatment of patients with vulvo-vaginal
      infections.

PMID- 11838278
TI  - Translocation and translaminar bioavailability of two neonicotinoid insecticides
      after foliar application to cabbage and cotton.
AB  - A laboratory study was undertaken to investigate the leaf systemic properties and
      the translaminar aphicidal activity of two commercialised neonicotinoid
      (chloronicotinyl) insecticides. For that purpose [14C]imidacloprid was subjected
      to uptake and translocation studies in cabbage and cotton after foliar
      application. Foliar penetration and short-term translocation patterns of
      imidacloprid were similar in both plant species. Nevertheless imidacloprid
      penetrated twice as much into cabbage leaves as it did into cotton leaves. It
      showed a comparable translaminar behaviour and was entirely translocated
      acropetally, indicating its well-known xylem mobility. The translaminar and
      acropetal movement of imidacloprid and acetamiprid were quantified by simple
      laboratory bioassays using the green peach aphid, Myzus persicae (Sulzer), and
      the cotton aphid, Aphis gossypii (Glover), as typical homopteran pests for
      cabbage and cotton, respectively. A single dose (7.5 micrograms AI per leaf)
      applied to the upper leaf surface of cabbage and cotton was tested against aphids
      feeding on the lower leaf surface both close to and distant from the site of
      application 1, 5 and 12 days after treatment. The translaminar residual activity
      of imidacloprid on cabbage leaves was superior to that of acetamiprid, whereas
      its translaminar efficacy against A gossypii on cotton was inferior to that of
      acetamiprid. However, oral ingestion bioassays using an artificial double
      membrane feeding system revealed no significant differences in intrinsic activity
      between the two neonicotinoids tested.

PMID- 11838279
TI  - The effect of foliar application of phosphonate formulations on the
      susceptibility of potato tubers to late blight.
AB  - Foliar sprays of potato plants with phosphonic acid (partially neutralised with
      potassium hydroxide to pH 6.4) substantially reduced infection of the tubers by
      Phytophthora infestans, the cause of late blight, in glasshouse and field
      experiments over a 4-year period. Healthy tubers of blight-susceptible cultivars
      removed from treated plants and artificially inoculated by spraying with
      sporangial/zoospore suspensions of P infestans did not develop disease symptoms,
      demonstrating that the phosphonate applications had directly reduced the
      susceptibility of tubers to infection, probably as a result of translocation into
      tuber tissue. In contrast, foliar application of fosetyl-aluminium did not
      significantly reduce tuber blight development following inoculation. Five to six
      sprays of partially neutralised phosphonic acid (2 kg ha-1) applied at 10-14 day
      intervals resulted in the least tuber infection, but such a treatment regime may
      not be economic. In trials where the effect of timing and rate of application of
      2-4 kg phosphonic acid ha-1 was examined, a single treatment of 4 kg ha-1 applied
      mid- or late-season proved the most effective. A spray programme in which one or
      two applications of phosphonic acid are combined with use of a non-systemic or
      systemic fungicide to enhance foliar protection offers the possibility of
      controlling both foliage and tuber blight and could have a major impact in
      reducing overwinter survival of P infestans in tubers.

PMID- 11838280
TI  - New, quick tests for herbicide resistance in black-grass (Alopecurus myosuroides
      Huds) based on increased glutathione S-transferase activity and abundance.
AB  - Black-grass (Alopecurus myosuroides Huds) is a major grass weed in winter cereals
      in Europe. It reduces yields and can act as a secondary host for a range of
      diseases. Herbicide resistance in this species was first detected in the UK in
      the early 1980s, and has now been reported in thirty counties. To successfully
      manage herbicide resistance it is vital that suspect populations are tested so
      that appropriate action can be taken. Ideally, a test will be quick, cheap and
      easy to use. Furthermore, it should provide an unequivocal result before post
      emergence herbicides are to be applied, allowing alternative strategies to be
      adopted where necessary. This paper reports the development of new tests for
      herbicide resistance based on our observation that the resistant black-grass
      biotype Peldon contains approximately double the activity of the enzyme
      glutathione S-transferase (GST) compared with susceptible biotypes. Data are
      presented on the production of a monoclonal antiserum to a novel 30 kDa GST
      polypeptide purified from the biotype Peldon. An ELISA using this antiserum is
      described and the utility of this assay to detect resistant black-grass biotypes
      in plants grown under glass and in the field is presented. In addition, a
      microtitre assay for GST activity is described, which allows the rapid assessment
      of GST activities of plants. Both abundance and activity of GSTs are discussed as
      markers for herbicide resistance in black-grass.

PMID- 11838281
TI  - Spatial variability in herbicide degradation in the subsurface environment of a
      groundwater protection zone.
AB  - The aim of this study was to investigate the spatial variability in degradation
      and mineralization of atrazine and isoproturon in subsurface samples taken from
      sandy loam soils overlying gravel terraces which form part of a groundwater
      protection zone. Percussion drilling was used to obtain samples from 11 boreholes
      (maximum depth 3 m). Unlabelled atrazine or isoproturon, and ring-14C-labelled
      atrazine or isoproturon were added to samples, incubated at 25 degrees C for up
      to 16 weeks, and analyzed for the residual herbicide or [14C]carbon dioxide. All
      samples showed the potential to degrade these herbicides, although the percentage
      degradation decreased by a factor of 2-3 from the surface soil to a depth of 3 m.
      This was associated with a decrease in organic matter content, but there was no
      change in the potential to mineralize acetate, indicating that specific changes
      in the catabolic ability of the microbial population occurred with depth. The
      capacity of samples to mineralize atrazine and isoproturon to carbon dioxide
      decreased markedly with depth, with no mineralization potential observed at a
      depth of 80 cm.

PMID- 11838282
TI  - Antimicrobial and pesticidal activity of partially purified flavonoids of Annona
      squamosa.
AB  - Foliar extracts of Annona squamosa (Family: Annonaceae) were screened for
      antimicrobial and insecticidal activity against the common microbial infestants
      of pulses and the stored grain pest pulse beetle, Callosobruchus chinensis
      (Coleoptera: Bruchidae). Flavonoids isolated from aqueous extracts of A squamosa
      showed antimicrobial activity against all the common microbial contaminants of
      pulses and 80% insecticidal activity against C chinensis at a concentration of
      0.07 mg ml-1. Various physico-chemical tests, chromatographic and spectroscopic
      studies with partially purified aqueous extract indicated the presence of
      flavonol type flavonoids. This may provide a useful beginning for the development
      of botanical pesticides for post-harvest safeguard of pulses.

PMID- 11838283
TI  - Efficacy and residues of phloxine B and uranine for the suppression of
      Mediterranean fruit fly in coffee fields.
AB  - The field efficacy of a bait containing phloxine B, uranine and Provesta 621
      protein was tested against Mediterranean fruit fly (Ceratitis capitata; Medfly)
      by aerial and ground spraying in about 84 ha of coffee fields in Kauai, Hawaii,
      USA. Concurrently, soil and crop samples were collected from the aerially sprayed
      field and its unsprayed control field for residue studies. Efficacy of the sprays
      was assessed through trapping with both protein-baited and trimedlure-baited
      traps and through the infestation level of coffee cherries collected at least
      three-quarters ripe. The C capitata population was low at the start of the aerial
      and ground spray studies, but dramatically increased in the control fields. This
      increase coincided with initial ripening of coffee cherries. During times of peak
      population levels, C capitata populations were reduced by more than 91% in the
      ground-sprayed field and 99% in the aerial-sprayed field, relative to the
      populations in their respective control fields and based on protein-baited trap
      catches. Results of residue analyses indicated that uranine dissipated quickly
      compared with phloxine B on coffee and soil. Coffee samples collected at pre
      spray periods had phloxine B residues of 7.2-25.5 ng g-1 on berries. Phloxine B
      concentrations were much higher on coffee leaves (163-1120 ng g-1). Lower
      concentrations of the dye were found from coffee samples collected during rainy
      days. Average phloxine B concentrations immediately after spraying were 56 and
      2840 ng g-1 in coffee berries and leaves, respectively. Dissipation of phloxine B
      on berries was fast, with a half-life (t1/2) of 3 days. Dissipation of phloxine B
      on leaves was fitted to two linear phases: the initial (0-4 days) with a shorter
      t1/2 of 3 days and the later phase (4-28 days) with a longer t1/2 of 15 days.
      Average concentrations of phloxine B in the top soil ranged from 50 to 590 ng g-1
      at pre-spray. Phloxine B initial concentration (770 ng g-1) reached a plateau
      immediately after the last spraying, but showed a steady decline over time with
      t1/2 of 16 days. Fast dissipation of the dyes in the field indicates that these
      chemicals may be environmentally compatible and therefore a promising alternative
      for fruit fly control.

PMID- 11838284
TI  - Lysimeter study to investigate the effect of rainfall patterns on leaching of
      isoproturon.
AB  - The influence of five rainfall treatments on water and solute leaching through
      two contrasting soil types was investigated. Undisturbed lysimeters (diameter
      0.25 m, length 0.5 m) from a sandy loam (Wick series) and a moderately structured
      clay loam (Hodnet series) received autumn applications of the radio-labelled
      pesticide isoproturon and bromide tracer. Target rainfall plus irrigation from
      the end of November 1997 to May 1998 ranged from drier to wetter than average
      (235 to 414 mm); monthly rainfall was varied according to a pre-selected pattern
      or kept constant (triplicate lysimeters per regime). Leachate was collected at
      intervals and concentrations of the solutes were determined. Total flow (0.27
      0.94 pore volumes) and losses of bromide (3-80% of applied) increased with
      increasing inputs of water and were larger from the Wick sandy loam than from the
      Hodnet clay loam soil. Matrix flow appeared to be the main mechanism for
      transport of isoproturon through the Wick soil whereas there was a greater
      influence of preferential flow for the Hodnet lysimeters. The total leached load
      of isoproturon from the Wick lysimeters was 0.02-0.26% of that applied. There was
      no clear variation in transport processes between the rainfall treatments
      investigated for this soil and there was an approximately linear relationship (r2
      = 0.81) between leached load and total flow. Losses of isoproturon from the
      Hodnet soil were 0.03-0.39% of applied and there was evidence of enhanced
      preferential flow in the driest and wettest treatments. Leaching of isoproturon
      was best described by an exponential relationship between load and total flow (r2
      = 0.62). A 45% increase in flow between the two wettest treatments gave a 100%
      increase in leaching of isoproturon from the Wick soil. For the Hodnet
      lysimeters, a 35% increase in flow between the same treatments increased
      herbicide loss by 325%.

PMID- 11838285
TI  - RunMACRO: a program to facilitate sensitivity analyses using the water flow and
      solute movement model MACRO.
AB  - Sensitivity analyses of pesticide leaching often involve a large range of
      simulations based on nearly identical set-ups. Using RunMACRO it is possible to
      make large numbers of simulations with a minimum of exertion. Running many nearly
      identical model set-ups is tedious and might introduce errors in selecting the
      correct values from a long range of parameter files that are appropriate to the
      model set-up. RunMACRO makes the task easier and minimises the risk of errors in
      the generation of parameter files and model executions. Using RunMACRO, it is
      possible to create a suite of MACRO simulations based on a single parameter file
      where the range or a list of values for one to three parameters is specified.
      RunMACRO then creates a parameter file for each of the simulations and runs the
      simulations one by one. RunMACRO can easily be modified to be used with other
      simulation programs that use ASCII-based parameter files and can be started from
      a command prompt. RunMACRO is available free to use and modify from the
      Geological Survey of Denmark and Greenland's home page.

PMID- 11838286
TI  - Dermal pharmacokinetics of the insecticide furathiocarb in rats.
AB  - The pharmacokinetics of furathiocarb were studied in vivo in male Sprague-Dawley
      rats following dermal treatment. HPLC and post-column derivatization were used
      for the analysis of furathiocarb and its metabolites (carbofuran, 3
      hydroxycarbofuran and 3-ketocarbofuran). Carbofuran and 3-hydroxycarbofuran were
      detected in plasma and urine rather than furathiocarb. 3-Ketocarbofuran, another
      potential metabolite, was not observed in any sample. The concentration of
      carbofuran was higher than that of 3-hydroxycarbofuran in plasma, but the reverse
      was the case in urine. The corresponding area under the plasma concentration-time
      curve, Tmax, and Cmax values of carbofuran and 3-hydroxycarbofuran for 1500 mg kg
      1 doses were 2.4-8.0 mg equiv hml-1, 12 h and 0.1-0.4 mg equiv ml-1,
      respectively. T1/2 was calculated only for 3-hydroxycarbofuran (28 h). Two
      metabolites were excreted in a dose-dependent manner without saturation.

PMID- 11838287
TI  - Mode of action of acibenzolar-S-methyl against sheath blight of rice, caused by
      Rhizoctonia solani Kuhn.
AB  - The mode of action of acibenzolar-S-methyl (BTH) was investigated against sheath
      blight of rice and its pathogen, Rhizoctonia solani. BTH exhibited limited
      fungitoxicity against R solani, in the form of reduced mycelial growth, hyphal
      browning and sclerotia formation. Parasite fitness of mycelia and sclerotia
      formed on BTH-amended media was also reduced. When applied as soil drench or
      foliar spray, BTH inhibited both disease development on inoculated sheaths and
      its spread to the younger sheaths. The degree of protection against sheath blight
      increased with increase in duration between BTH application and inoculation. The
      curative effect of BTH was poor. When applied through roots a protective effect
      of BTH was visible even with only a 1-h interval between application and
      inoculation. However, in the case of foliar application, protective effect was
      recorded only when the gap between application and inoculation was 24 h. BTH
      reduced the frequency of penetration by R solani, colonization of host tissue and
      spread of the hyphae from primary lesions to form secondary lesions. BTH induced
      swelling of hyphal tips on the sheath surface, formation of papillae, browning of
      penetrated epidermal cells and degeneration of intra-cellular hyphae colonizing
      epidermal and mesophyll cells. Therefore, the protective effect of BTH against
      sheath blight was due to combination of its host defence-inducing activity and
      its adverse effect on growth and vigor (parasite fitness) of the pathogen.

PMID- 11838288
TI  - An ecological risk assessment for spinosad use on cotton.
AB  - Spinosad is a reduced-risk insecticide with a novel mode of action that provides
      an alternative to older classes of insecticides such as organophosphates,
      carbamates and pyrethroids. A comprehensive ecological risk assessment for
      spinosad use in US cotton crops is presented within a framework of tiered levels
      of refinement following the guidelines of the US EPA for ecological risk
      assessments. Toxicity information for a variety of species is documented and
      utilized, environmental concentrations estimated, and risk characterizations in
      the form of risk quotients are quantified. Results indicate that spinosad use in
      cotton does not exceed the most conservative Tier I levels of concern (LOC)
      values for groundwater, mammals and birds or acute risk to aquatic organisms. Use
      of very conservative Tier I screening methods resulted in exceeding LOC values
      for chronic exposure for some aquatic organisms, thus prompting further
      refinement. When the exposure prediction was refined using less conservative,
      Tier II mechanistic environmental fate transport models to predict offsite
      transport and environmental concentrations, chronic risk was not predicted for
      these species. Spinosad is acutely toxic to bees under laboratory conditions, but
      toxicity of residue studies and field studies indicate that under actual use
      conditions the impact on bees is minimal.

PMID- 11838289
TI  - Persistence and performance of esfenvalerate residues on broccoli.
AB  - The efficacy of esfenvalerate (84 g litre-1 EC; Asana XL) at 7.0 g AI ha-1 on
      broccoli was tested against the flea beetle, Phyllotreta cruciferae Goeze
      (Chrysomelidae: Coleoptera) and the imported cabbage worm, Pieris rapae L
      (Pieridae: Lepidoptera) under field conditions. Insect populations were monitored
      before and after treatment. Periodic sweep-net collections and examination of the
      leaves in treated and untreated broccoli plots revealed mean reductions of P
      cruciferae levels of nearly 98% 1 week post-application compared with untreated
      plots. The residual toxicity of esfenvalerate was also effective for 2 weeks in
      reducing population density of P rapae by 69% on broccoli leaves. The impact of
      esfenvalerate on feeding damage to broccoli leaves was established by counting
      the number of feeding holes made by P cruciferae on spring broccoli and P rapae
      on fall broccoli. As the leaf area ingested increased, a linear relationship was
      seen between the number of holes and number of insects. Results indicated that
      forage destruction by the two pests was significantly reduced by esfenvalerate
      application. Esfenvalerate was extracted from broccoli at 1 h and 1, 3, 7, 10,
      and 14 days post-application for residue analysis. Residues on spring broccoli
      were 12.2, 5.2 and 2.9 micrograms cm-2 on the leaves and 0.13, 0.05 and 0.02
      microgram g-1 on the heads at 1 h, 1 and 3 days, respectively. Only trace levels
      (0.001 microgram g-1) were detected in/on the heads 14 days after spraying. On
      the basis of half-life (T1/2) values, persistence of esfenvalerate on spring
      broccoli leaves (T1/2 = 1 day) was shorter than on fall broccoli (T1/2 = 1.6
      days). T1/2 values were 2.1 and 3.6 days on spring and fall broccoli heads,
      respectively. The implications of these residue levels on re-entry times into
      treated fields are discussed.

PMID- 11838290
TI  - Toxicity of a formulation of the insecticide indoxacarb to the tarnished plant
      bug, Lygus lineolaris (Hemiptera: Miridae), and the big-eyed bug, Geocoris
      punctipes (Hemiptera: Lygaeidae).
AB  - Indoxacarb is a new oxadiazine insecticide that has shown outstanding field
      insecticidal activity. The toxicity of a 145 g litre-1 indoxacarb SC formulation
      (Steward) was studied on the tarnished plant bug Lygus lineolaris and the big
      eyed bug Geocoris punctipes. Both insect species responded very similarly to
      indoxacarb in topical, tarsal contact and plant feeding toxicity studies. The
      topical LD50 of the formulation was c 35 ng AI per insect for both species.
      Prolonged tarsal contact with dry indoxacarb residues did not result in mortality
      for either insect species. However, both species were susceptible to feeding
      through dried residues of indoxacarb after spraying on young cotton plants.
      Feeding on water-washed plants resulted in lower mortality than that observed
      with unwashed plants, and toxicity declined even more dramatically after a,
      detergent rinse, indicating that much of the indoxacarb probably resides on the
      cotton leaf surface or in the waxy cuticle. These results were corroborated by
      HPLC-mass spectrometry measurements of indoxacarb residues on the plants. Greater
      mortality for both species was observed in a higher relative humidity
      environment. Higher levels of accumulated indoxacarb and its active metabolite
      were detected in dead G punctipes than in L lineolaris after feeding on sprayed,
      unwashed plants. When female G punctipes ate indoxacarb-treated Heliothis zea
      eggs, there was significant toxicity. However, only c 15% of the females consumed
      indoxacarb-treated eggs, and the rest of the females showed a significant
      diminution of feeding in response to the insecticide. Cotton field studies have
      shown that indoxacarb treatments at labelled rates lead to a dramatic decline in
      L lineolaris, with negligible declines in beneficial populations. A major route
      of intoxication of L lineolaris in indoxacarb-treated cotton fields thus appears
      to be via oral, and not cuticular, uptake of residues from treated cotton plants.
      The mechanisms for selectivity/safety for G punctipes are currently under
      investigation and may be a combination of differential feeding behavior and
      diminution of feeding by females exposed to indoxacarb-treated eggs.

PMID- 11838291
TI  - [Genomic methods for identification of traits and inherited disorders in farm
      animals].
AB  - In this review we demonstrate the interaction of the blueprint of an individual
      (the genome, genomic DNA), its phenotype and the environment. The phenotype
      consists of quantitative (e.g. growth, milk yield) or functional characteristics
      e.g. fitness, longevity, fertility and disease resistance. The latter
      characteristics influence the welfare of an animal substantially. As only the
      genetically determined part of a particular characteristic is transferred from
      one generation to the next, it is important to know what the genetic variants
      (alleles) of the parents at one or more gene loci are. New methods in molecular
      biology have made it possible to localize and characterize important genes which
      help to breed more efficient and healthy animals. The exact characterization of
      the phenotype is vital in identifying genes with major effects and therefore the
      cooperation with experts from veterinary medicine, biochemistry, and biology is
      indispensable. As well as an overview of available genetic tests in farm animals,
      we show various examples how to identify the molecular basis of a particular
      phenotype and how to use the results in practical breeding programs. Genetic
      diagnosis enables the breeder to identify undesired alleles early and hinders
      therefore its uncontrolled distribution in the population. In the long term this
      leads to a smaller number of affected animals and depending on the disease it may
      help to prevent animals from suffering.

PMID- 11838292
TI  - [Efficacy of probiotic feed additives: guidelines for the evaluation of the
      efficiency of microorganisms in dogs, cats, and horses].
AB  - Probiotic microorganisms are frequently in use as feed additives for farm and pet
      animals. For admission for the common market products have to be tested according
      to the feed additive directive 70/524/EC. The dossier for admission has to
      comprise data of efficiency as laid down in the directive 87/153/EC. During the
      last years it became obvious after the evaluation of several dossiers, that no
      definitive criteria for the assessment of efficacy were available for dogs, cats
      and horses (84/153/EC). Aspects like the promotion of animal production are not
      relevant in this context. Therefore, the European commission launched the
      directive for the evaluation of efficacy of microorganisms for dogs, cats and
      horses, that supports the evaluation of microbial feed additives and which is
      described in this paper.

PMID- 11838293
TI  - Emergency-culling and mortality in growing/fattening pigs in a large Hungarian
      "farrow-to-finish" production unit.
AB  - The trial was carried out in a large Hungarian 2000 sow "farrow-to-finish"
      production unit. Out of a total number of 15,841 evaluated growing/finishing
      pigs, 1319 pigs died or were emergency-culled and were post-mortem routinely
      examined. For the purpose of this study the emergency-culling and mortality were
      recorded into the same category. The average annual emergency-culling/mortality
      rate was unusual high (8.62%). Five body condition related categories were
      registered. The majority of the mortality comprised animals of body condition
      "below average", representing 891 pigs (67.56%) and "average" (407 pigs =
      30.85%). The rest of the examined animals comprised 17 pigs (1.29%) "emitted", 2
      pigs "kachexia" (stunted pig) or "fat" (0.15% each). The overall study showed
      that gastrointestinal tract disorders (395 animals = 29.95%) were the most
      frequently recorded cause of emergency-culling or mortality. Both inflammatory
      disorders (7.66%) and rectal stricture (7.51%) were in this category the most
      frequent diagnosis followed by rectal prolapse (5.92%). Gastric ulcers comprised
      4.55% of the necropsied animals. Torsion of abdominal organs and miscellaneous
      cases represented slightly more than 2% of the post-mortem examined pigs. Lesions
      which involved the respiratory system, comprised 14.85% of the necropsied pigs.
      Bronchopneumonia due to Mycoplasma hyopneumoniae occurred in 5.61%, embolic
      suppurative or necrotic pneumonia in 4.78% and pleuropneumonia due to
      Actinobacillus pleuropneumoniae in 3.1% of the cases. Diseases involving the
      urinary system were diagnosed in 21 cases (1.59%). Five cases of skin disorders
      were registered (0.38%). Cardiovascular disorders were represented by congestive
      heart failure (31 pigs = 2.35%), pericarditis (22 animals = 1.66%) or
      endocarditis (21 pigs = 1.60%). Cardiomyopathy was found in 15 (1.2%) animals.
      Lesions involved the locomotor system ranked second of all cases (15.92%). Claw
      lesions accounted 13.72%, arthritis 2.13% of the animals and luxation or fracture
      was diagnosed only in one case (0.07%). Systemic infections were reported in 96
      cases (7.28%) including polyserositis (4.09%), erysipelas, edema disease or
      miscellaneous causes (each category slightly more than 1%). Genetic problems were
      involved in 8.19% of the fatal cases and social stress or cannibalism related
      culling or mortality comprised 37 animals (2.81%). In 161 cases (12.20%) of the
      mortality the causes of death were not established. Two or more lesions related
      to culling or mortality were found in 320 pigs (24.26%, p < 0.001). The most
      common diagnosed pathologic changes in association with other lesions were
      Mycoplasma hyopneumoniae caused bronchopneumonia (4.09%), embolic suppurative or
      necrotic pneumonia (4.55%), followed by inflammatory gastrointestinal problems
      (3.10%), gastric ulcer (2.35%), claw lesions (2.19%) and arthritis (1.14%). It
      appears from the presented study that a routine post-mortem examination of all
      emergency-culled or dead pigs over a long period of time gives a clear picture of
      causes of mortality enabling the management to plan management strategies as
      vaccination programs, genetic improvements and optimising environmental
      conditions.

PMID- 11838294
TI  - [Duration of pregnancy and diurnal distribution of lambing in sheep with
      different genotypes].
AB  - Based on 1103 lambings the duration of pregnancy was determined for the breeds
      German Mutton Merino, German Blackhead Mutton and their Booroola crosses.
      Furthermore the influence of age and body mass of the ewes as well as number, sex
      and body mass of the born lambs were considered. German Blackhead Mutton have
      with 145/146 days on average a 4-5 days shorter duration of pregnancy than German
      Mutton Merino with 150 days. The examined effects influenced the pregnancy
      duration only insignificantly or not at all. An influence of the breed, however,
      was determined. In the pen with limited light during the night all genotypes
      lambed mostly between 9.00 a.m. and 3.00 p.m. During the day time 12-26% more
      ewes lambed than during the remaining 12 hours of the day.

PMID- 11838295
TI  - [Ca and P supply of ruminants in the 19th and beginning of 20th century in Middle
      Europe].
AB  - The present review evaluates veterinary publications about some bone diseases in
      ruminants till 1925. According to more than 100 publications in some regions of
      Germany as well as in Scandinavian and Westeuropean countries during the 19th
      century several cases of bone fractures in ruminants were reported, mainly in
      pregnant and lactating cattle and goats. From a recent point of view and after
      feed analyses this disease obviously was caused by a P-deficiency. Bone fractures
      sometimes were accompanied by licking behaviour, but in other regions pica
      (without severe skeletal deformations) was probably related to a Cu- or Co
      deficiency. Swelling of the jaws (probably by Ca-deficiency) was exclusively
      described in goats. By preventive measures (feeding bone meal, P-fertilisation)
      bone fractures diminished in the beginning of the 20th century. After the
      experience in the past in ruminants bone diseases may come back, if effective
      preventive measures will be ignored due to the recent trends towards 'natural
      farming'.

PMID- 11838296
TI  - [Relaxin: an important indicator of canine pregnancy].
AB  - In the present study the concentration of relaxin in peripheral blood plasma was
      assessed during canine pregnancy for its suitability as a pregnancy indicator,
      using a newly developed relaxin enzyme immunoassay. A significant relaxin
      increase was found in pregnancy at day 24 after ovulation. However, this relaxin
      increase did not correlate either with litter size or with body weight of the
      bitch. Induction of abortion with prostaglandin F2 alpha resulted in reduced
      peripheral relaxin levels, suggesting a damage of the placenta due to this
      medical intervention. Thus, the results confirm that relaxin, which is produced
      by the placenta, is a useful marker for early pregnancy diagnosis in the bitch.
      Relaxin measurement is recommended for detection of pregnancy either alone, or as
      supplement of ultrasonographic findings.

PMID- 11838298
TI  - The evolution of quality management in state Medicaid agencies: a national survey
      of states with comprehensive managed care programs.
AB  - BACKGROUND: Concern has been expressed about whether managed care health plans
      can successfully meet the special needs of Medicaid beneficiaries. A 1996 survey
      indicated that state Medicaid agencies had just begun conducting quality
      oversight and management. Since then the federal government has released
      guidelines under the Quality improvement System for Managed Care (QISMC) program
      to assist states with quality management of managed care programs. In 1999 a
      follow-up telephone survey was conducted with representatives from 45 states to
      describe the current state of and changes in quality management activities by
      state Medicaid agencies for Medicaid beneficiaries enrolled in managed care.
      RESULTS: The 45 states represented a 50% increase between 1995 and 1999. The
      number of states enrolling the disabled had doubled (from 15 to 30). Most states
      collecting data on satisfaction and childhood immunizations fed it back to health
      plans, although feedback of other measures of access and quality occurred less
      frequently and fewer states provided information to beneficiaries choosing health
      plans. Fewer than 25% of states reported having even one health plan demonstrate
      improvement in individual measures of access and quality except for prenatal care
      (28%) and childhood immunizations (33%). Fewer than half of the states included
      contractual penalties in their contracts with health plans, and very few (three
      or fewer per penalty) had over invoked such penalties. CONCLUSIONS: State
      Medicaid agencies continue to adapt to their new roles as value-based purchasers
      of health care. Although increasing numbers of states collect data on
      satisfaction, access, and quality of care, few states have been able to document
      improved performance in the health plans they oversee.

PMID- 11838299
TI  - Using the Internet to teach consumers about quality care.
AB  - BACKGROUND: The Internet is an important source of health information for
      consumers. Patients can learn about their diagnoses, review treatments and
      medications, and locate other health information for themselves and their
      families. Information about quality care can also be found on the Internet. Few
      consumers, though, use these Web sites for learning about quality care. SEARCH
      FOR WEB SITES ON QUALITY CARE: In 2000 the investigators searched the Internet
      and generated a list of approximately 90 relevant Internet documents under the
      broad heading of quality health care. They then pared the list to 34, by using
      the Health Information Technology Institute (HITI) criteria. TESTING OF INTERNET
      DOCUMENTS BY CONSUMERS: In the second phase of the project, 5 of the 34 Internet
      documents were tested by a convenience sample of 32 consumers. Most of the
      participants had experience in using the Internet, although generally not in the
      area of quality care. They found the Web sites easy to use and indicated that the
      Internet resources would help them assess the quality of care they receive from
      physicians, nurses, and others. DISCUSSION: Web sites need to be evaluated to
      ensure that the information they provide is accurate and current, among other
      criteria. All patients should understand their health benefits and the importance
      of making informed decisions about their health care, as well as how quality care
      is measured, how to use quality reports, how to choose providers and hospitals,
      how to assess the quality of their own care and be more involved in it, and what
      they should do when faced with new diagnoses.

PMID- 11838297
TI  - Coaching and leadership for the diffusion of innovation in health care: a
      different type of multi-organization improvement collaborative.
AB  - BACKGROUND: Health care organizations have suffered a steady decrease in
      operating margins in recent years while facing increased competition and pressure
      to provide ever-higher levels of customer service, quality of care, and
      innovation in delivery methodologies. The ability to rapidly find and implement
      changes that will lead to strategic improvement is critical. To assist member
      organizations in dealing with these issues, VHA Upper Midwest launched the
      Coaching and Leadership Initiative (VHA-CLI) in January 1999. The initiative was
      intended to develop new methods of collaborating for organizational learning of
      best practices, with a focus on generalizable change and deliberate leadership
      supports for deployment, diffusion, and sustainability. The emphasis was on the
      spread of ideas for improvement into all relevant corners of the organization.
      STRUCTURE AND PROCESS OF THE COLLABORATIVE: The structure of the VHA-CLI
      collaborative involved four waves of demonstration teams during 2 years. Each
      meeting of the collaborative included an executive session, team learning
      sessions (concepts applied to their improvement projects), and planning for the 6
      month action period following the meeting. An important feature of the
      collaborative is the way in which teams in the various waves overlapped. For
      example, the Wave 1 team for a given organization came to a learning session in
      January 1999. At the second collaborative meeting in June 1999, the Wave 1 teams
      reported on the progress in their pilot sites. This meeting was also the kick-off
      session for the Wave 2 teams, which could learn about organizational culture and
      the improvement model from the efforts of their colleagues on Wave 1. Wave 1
      teams also learned about and planned for spreading their efforts to other sites
      beyond the pilot. The pattern of multiple teams stretching across two waves of
      activity was repeated at every meeting of the collaborative. SUCCESS: Each
      organization in the collaborative has achieved improved outcomes around its
      selected clinical topics. In total, 26 teams have made significant improvement in
      17 different topic areas. In addition, each organization has been able to
      successfully spread tested improvements to other individuals, teams, or
      locations, and the improvement work has become easier and more rapid with each
      successive cycle. CONCLUSIONS: The learning process initiated by this project
      will continue for at least another year in the VHA Upper Midwest region and will
      be expanded as participating organizations in other regions enroll in the VHA's
      national effort.

PMID- 11838300
TI  - Using control charts to assess performance measurement data.
AB  - BACKGROUND: In 1997 the Joint Commission on Accreditation of Healthcare
      Organizations (JCAHO) announced the ORYX initiative, which integrates outcomes
      and other performance measurement data into the accreditation process. JCAHO uses
      control and comparison charts to identify performance trends and patterns that
      are provided to JCAHO surveyors in advance of the organization's survey. During
      its survey, the health care organization (HCO) is asked to explain its rationale
      for its selection of performance measures, how the ORYX data have been analyzed
      and used to improve performance, and the outcomes of these activities. WHAT DO
      CONTROL CHARTS DO? Control charts indicate whether an HCO's process is in
      statistical control (that is, stable insofar as only common cause variation
      exists) or out of statistical control (that is, unstable insofar as special cause
      variation exists). With the presence of special cause variation, the HCO should
      not make any change in its processes until the special cause is identified and
      eliminated. CHOOSING THE CORRECT CONTROL CHART: An HCO can use many different
      control charts. Selecting the correct control chart type for the type of data
      collected makes interpretation more sensitive for detecting special cause
      variation. The ORYX measures are calculated as proportions (rates), ratios, and
      means (continuous variables data, such as average length of stay), and this
      information forms the basis for selecting the correct type of control chart. In
      addition, the average rate (especially for rare event measures) and the average
      number of cases need to be considered when selecting the control chart type for
      small population measures.

PMID- 11838301
TI  - Early warning and response network (EWARN), southern Sudan.

PMID- 11838302
TI  - The deliberate use of biological and chemical agents to cause harm: public health
      response.

PMID- 11838303
TI  - Frederick P. Zuspan, M.D. A tribute on his 80th birthday.

PMID- 11838304
TI  - A new monophasic oral contraceptive containing drospirenone. Effect on
      premenstrual symptoms.
AB  - OBJECTIVE: To determine whether a new monophasic oral contraceptive containing
      drospirenone/ethinyl estradiol reduces premenstrual symptoms. STUDY DESIGN: In an
      open-label study measuring intrasubject changes in premenstrual symptoms and
      comparing effects between women who were new users of oral contraceptives and
      those who switched from previous contraceptives, ethinyl estradiol (30
      micrograms) and drospirenone (3 mg) were administered for 13 menstrual cycles to
      326 healthy women aged 18-35 years. Subjects completed the 23-item Women's Health
      Assessment Questionnaire at baseline and at the end of the sixth cycle. RESULTS:
      At the end of cycle 6, premenstrual and menstrual symptom scores on the negative
      affect and water retention scales were reduced significantly relative to
      baseline, as was increased appetite during the premenstrual and menstrual phases.
      Similar improvements were seen among new users of hormonal contraceptives and
      those who switched from previous contraceptives. Impaired concentration scale
      scores were not significantly reduced from baseline, and assessments of undesired
      hair changes and feelings of well-being did not change appreciably. CONCLUSION:
      An oral contraceptive containing drospirenone/ethinyl estradiol may reduce the
      premenstrual symptoms of negative affect, water retention and increased appetite.

PMID- 11838305
TI  - Labor induction after fetal death. A retrospective analysis.
AB  - OBJECTIVE: To describe the delivery outcomes in patients with stillborn infants
      after labor induction versus spontaneous onset of labor. STUDY DESIGN: A
      retrospective chart review was performed of singleton pregnancies complicated by
      fetal death over a three-year period when awaiting spontaneous onset of labor was
      a common practice. Exclusion criteria were prior multiple cesarean deliveries,
      placenta previa, preeclampsia or suspected abruptio placentae. Outcome measures
      included time spent in the labor and delivery unit and rates of maternal
      hemorrhagic morbidity and endomyometritis. RESULTS: Two hundred eight patients,
      100 patients undergoing labor induction and 108 with spontaneous onset of labor,
      met the study criteria. Patients delivering after induction spent a longer time
      in the labor and delivery unit (13.7 versus 4.4 hours). The endomyometritis rate
      was higher in the spontaneous labor group (6% versus 1%). There were no
      differences in the frequency of postpartum hemorrhage, retained placenta or need
      for blood transfusion. CONCLUSION: Induction following diagnosis of fetal death
      is safe and may reduce maternal infectious morbidity.

PMID- 11838306
TI  - Outcome of prenatally diagnosed fetal hydronephrosis.
AB  - OBJECTIVE: To demonstrate the postnatal investigation, treatment and outcome of
      infants with hydronephrosis prenatally diagnosed by ultrasound between 1994 and
      1996. STUDY DESIGN: In a two-year period we studied 20 infants who presented with
      hydronephrosis diagnosed by prenatal ultrasound and confirmed by postnatal
      ultrasound. Unilateral hydronephrosis was diagnosed in 17 infants and bilateral
      hydronephrosis in 3. An anteroposterior renal pelvic diameter > 7 mm after 33
      weeks of pregnancy was used to predict abnormal outcomes. In the postnatal follow
      up period, the infants were followed with sequential ultrasound and urinalysis.
      99mTc-diethylene triamine pentaacetic acid scan, intravenous pyelography and
      voiding cystourethrography were performed in selected cases. Pyeloplasty was
      performed only if there was evidence of renal compromise. RESULTS: A male
      predilection was found. The left kidney was more commonly involved. Ultrasonic
      follow-up of the 20 infants showed that hydronephrosis resolved in 9, who were
      all in the unilateral hydronephrosis group. The range of fetal renal pelves on
      prenatal ultrasound was 7-15 mm in the resolution group. Pyeloplasty was
      performed in three unilateral hydronephrosis infants. Follow-up ranged from 36 to
      72 months. CONCLUSION: When the fetal renal pelvis was < 15 mm on prenatal
      ultrasound, it never progressed. Prenatally diagnosed hydronephrosis may be
      safely observed, and surgical correction should be performed only if renal
      compromise occurs.

PMID- 11838307
TI  - Cold knife conization vs. LEEP. Are they the same procedure?
AB  - OBJECTIVE: To prospectively evaluate the amount of tissue removed at loop
      electrosurgical excision procedure (LEEP) vs. cold knife conization. STUDY
      DESIGN: Forty consecutive LEEP or cold knife conization specimens were
      prospectively measured and weighed by a single pathology technician. Diameter,
      length and weight of the specimens were compared using Student's t test. RESULTS:
      Mean diameter of cold knife cone specimens was 2.6 vs. 2.2 cm for LEEP (P = .07).
      Mean length of cold knife cone specimens was 1.5 vs. 1.0 cm for LEEP (P = .001).
      Mean weight for cold knife cone specimens was 4.4 vs. 2.0 g for LEEP (P = .001).
      CONCLUSION: In a prospective evaluation, cold knife cone specimens were 50%
      longer and 100% heavier than LEEP specimens.

PMID- 11838308
TI  - Laparoscopic management of adnexal masses. Safety and effectiveness.
AB  - OBJECTIVE: To evaluate the effectiveness and safety of the laparoscopic approach
      to adnexal masses. STUDY DESIGN: Sixty-one patients who underwent laparoscopic
      intervention due to various types of adnexal masses between March 1997 and April
      1999 in a teaching hospital were assessed retrospectively. Patients with strong
      evidence of advanced ovarian cancer, such as large masses, ascites or omental
      cake, were excluded. Frozen section was performed intraoperatively, if indicated.
      In cases of malignancy, laparotomy was performed. RESULTS: Mean operation time
      was 67.2 minutes; average hospital stay was 1.2 days. Cyst enucleation was
      performed in 34% of patients. Two of 61 patients were diagnosed as having
      malignant disease and converted to laparotomy. Chemical peritonitis was
      encountered after dermoid cyst removal due to spillage of contents in spite of
      using an endobag and irrigating copiously with saline. No other complications
      were seen. CONCLUSION: Laparoscopy is a safe approach to adnexal masses and may
      decrease the rate of unnecessary laparotomies for benign cysts, which give no
      suspicious ultrasonographic signs.

PMID- 11838309
TI  - Total hysterectomy for a nonprolapsed, benign uterus in women without vaginal
      deliveries.
AB  - OBJECTIVE: To compare the different techniques of hysterectomy for a
      nonprolapsed, benign uterus in women without vaginal deliveries. STUDY DESIGN: A
      retrospective study in a university hospital analyzed 148 total hysterectomies in
      women without vaginal deliveries performed from August 1991 to June 2000. Forty
      four patients had had cesarean sections (29.7%), and 104 (70.3%) were
      nulliparous. Twenty-four patients had had abdominal myomectomies (16.2%). The
      vaginal route (group 1) was used for 77 patients (52%), 56 (37.8%) had
      laparotomies (group 2), and 15 (10.2%) had laparoscopically assisted vaginal
      hysterectomies (group 3). RESULTS: The uterine weight was 275 (+/- SD 140) g in
      group 1, 830 (+/- SD 1620) in group 2 and 331 (+/- SD 160) in group 3. Mean
      operation time was 87 (+/- SD 76) minutes in group 1, 96 (+/- SD 41) in group 2
      and 112 (+/- SD 56) in group 3. There was one serious complication with the
      vaginal route (sigmoid injury). The hospital stay was 4 (+/- SD 3.1) days in
      group 1, 7.1 (+/- SD 3.8) in group 2 and 4.3 (+/- SD 1.5) in group 3. CONCLUSION:
      Vaginal hysterectomy for a nonprolapsed, benign uterus is indicated for women
      without vaginal deliveries and is feasible in 72% of cases in our recent
      experience, with a low complication rate. Training in vaginal surgery should
      allow safe performance of the procedure at most centers.

PMID- 11838310
TI  - In vitro antagonistic effect of Lactobacillus on organisms associated with
      bacterial vaginosis.
AB  - OBJECTIVE: To assess antagonistic properties of Lactobacillus strains isolated
      from the vaginas of healthy women as compared to the most common bacterial agents
      related to vaginosis. STUDY DESIGN: Antagonistic activity of different
      Lactobacillus strains isolated from the vaginas of healthy women not treated for
      infections with an antibiotic for the previous three months was screened using an
      agar slab method. The activity was tested against test organisms associated with
      bacterial vaginosis and/or urinary tract infections: Staphylococcus aureus,
      Enterococcus faecalis, Streptococcus agalactiae, Escherichia coli, Gardnerella
      vaginalis, Peptostreptococcus anaerobius and Prevotella bivia. RESULTS: Many of
      the 146 Lactobacillus strains tested exerted apparent antagonistic activities
      against gram-positive aerobic cocci and gram-negative rods, such as S aureus and
      E coli, and a marked number of Lactobacillus strains inhibited facultative
      bacteria, such as Gardnerella vaginalis and the anaerobes P anaerobius and P
      bivia. Only a few lactobacilli were able to inhibit growth of E faecalis and S
      agalactiae. Indicator bacteria growth inhibition probably relies upon several
      different complementary mechanisms. The specific indicator bacteria species
      determines which mechanism predominates. CONCLUSION: Lactobacillus strains taken
      from normal vaginal flora demonstrated antagonistic activity against a variety of
      bacteria related to vaginal and urinary tract infections. The specific occurrence
      rates of active Lactobacillus strains are different, and this difference is
      dependent on the indicator bacteria species.

PMID- 11838311
TI  - Fibrolamellar hepatic carcinoma with a presentation similar to that of septic
      pregnancy. A case report.
AB  - BACKGROUND: Of hepatocellular carcinomas, produce quantifiable levels of beta
      hCG. CASE: A 44-year-old woman presented with fever, abdominal pain, vaginal
      bleeding and increased serum levels of beta-hCG. CONCLUSION: Nongestational
      elevations of serum beta-hCG warrant consideration of a malignant neoplasm.

PMID- 11838312
TI  - Cesarean scar endometriosis. A report of two cases.
AB  - BACKGROUND: Extrapelvic endometriosis is a fairly rare phenomenon. The majority
      of extrapelvic endometriosis involves scar tissue following obstetric/gynecologic
      procedures. Cesarean section scar endometriosis may be more common than reflected
      in the literature and has a distinct presentation and treatment. CASES: Two
      patients with histories of cesarean sections presented with a painful, enlarging
      mass involving the cesarean section scar. The pain was cyclic and strongest just
      prior to menstruation. Both patients were treated with surgical excision, and
      both specimens had endometriosis confirmed by histopathology. CONCLUSION:
      Endometriosis involving a cesarean section scar may be more common than thought.
      Patients typically present with a history of cesarean section or other
      obstetric/gynecologic surgery and are found to have a mass involving the scar,
      with symptoms intensifying prior to each menstrual cycle. Surgical excision is
      the treatment of choice, providing both diagnostic and therapeutic intervention.

PMID- 11838313
TI  - Impact of pregnancy on respiratory capacity in women with muscular dystrophy and
      kyphoscoliosis. A case report.
AB  - BACKGROUND: Restriction of the chest wall in pregnancy prevents adaptive
      physiologic hyperventilation. This in turn might gradually promote respiratory
      insufficiency. CASE: Two consecutive pregnancies occurred in a woman with severe
      kyphoscoliosis due to juvenile muscular dystrophy. The patient died postpartum.
      CONCLUSION: Pregnancies with restrictive lung diseases, including severe
      scoliosis and kyphoscoliosis, should be considered high risk and thus should be
      monitored and managed carefully.

PMID- 11838314
TI  - Successful pregnancy outcome in a lung transplant recipient with tacrolimus
      immunosuppression. A case report.
AB  - BACKGROUND: The use of tacrolimus (FK506, PROGRAF) in pregnant lung transplant
      recipients has been very rarely reported. CASE: A 32-year-old woman, gravida 1,
      para 0, had previously undergone a unilateral lung transplant secondary to
      pulmonary fibrosis. Four years later she spontaneously conceived. During
      pregnancy, she was maintained on an immunosuppressive regimen of tacrolimus and
      prednisone. Bi-weekly pulmonary function testing remained unchanged until 34
      weeks' gestation. At that time, labor was induced due to concern for allograft
      rejection. A healthy, 2,208-g, female infant was born via an uncomplicated
      vaginal delivery. Postpartum transbronchial biopsy showed minimal acute cellular
      rejection. CONCLUSION: Lung transplant recipients may achieve successful
      pregnancy outcomes with the use of tacrolimus.

PMID- 11838315
TI  - Thin-layer Pap test vs. conventional Pap smear. Analysis of 400 split samples.
AB  - OBJECTIVE: To analyze our experience with 400 Thin-Prep (TP) split samples (Cytyc
      Corp., Boxborough, Massachusetts) as an initial assessment of this new
      technology's effect in our laboratory. STUDY DESIGN: Three gynecologic
      oncologists and two general gynecologists obtained the 400 split samples using a
      broom sampling device. Following conventional smear (CS) preparation, they rinsed
      the broom in Preservcyt solution (Cytyc) for subsequent TP processing. The paired
      samples were separated, independently analyzed and classified by the Bethesda
      System. All available follow-up surgical pathology material was reviewed and
      compared to the cytologic diagnoses. RESULTS: TP had significantly more abnormal
      results (22% vs. 16%, P = .007), including more atypical squamous cells of
      undetermined significance (ASCUS) (9.5% vs. 6.3% P = .07) and low grade squamous
      intraepithelial lesion (LSIL) (7.8% vs. 5.3%, P = .03). Both methods had 3.3%
      high grade squamous intraepithelial lesion (HSIL). For TP, ASCUS/squamous
      intraepithelial lesion (SIL) = 0.86 and for CS, ASCUS/SIL = 0.74. Ten TP SILs had
      a paired negative CS, including LSIL (nine cases) and HSIL (one case). Consensus
      review of these 10 TP slides confirmed the HSIL and four LSILs. No CS SILs had a
      paired negative TP. Only 36 (9%) cases had surgical pathology follow-up. The
      surgical specimens included 17 cervical intraepithelial neoplasia (CIN) 2 or
      above. The TP method had no false negatives, while the CS method had 3 false
      negatives among the 17 confirmed cases of CIN 2 or above. CONCLUSION: TP appears
      to be superior to CS for detecting SILs.

PMID- 11838316
TI  - Tartary buckwheat flavonoid activates caspase 3 and induces HL-60 cell apoptosis.
AB  - It has been proposed that flavonoids may have potential as anticancer agents. In
      this study, we showed that tartary buckwheat flavonoid (TBF) obviously inhibits
      the growth of human acute myelogenous leukemia (AML) HL-60 cells by MTT assay.
      The inhibitory effect of TBF on the proliferation of HL-60 cells is related to
      the induction of apoptosis, which is confirmed by DNA ladder formation on gel
      electrophoresis and apoptosis morphological changes under light microscope.
      Furthermore, HL-60 cells undergo rapid apoptosis upon treatment with TBF, as
      indicated by increased annexin V binding capacity and caspase 3 activation with
      flow cytometric analysis. Thus, our data provide a potential mechanism for the
      chemopreventive activity of tartary buckwheat flavonoid and suggest that it may
      have a potentially therapeutic role for human leukemia.

PMID- 11838318
TI  - Lipopolysaccharide-mediated immobility in mice: reversal by cyclooxygenase enzyme
      inhibitors.
AB  - Endotoxin (lipopolysaccharide, LPS) is known to activate the hypothalamo
      pituitary adrenocortical axis, as well as norepinephrine and indolamine
      metabolism. In the present study we examined the effects of systemically
      administered LPS on forced swimming-induced despair behavior in mice. LPS (50
      micrograms/mouse i.p.) time-dependently enhanced the forced swimming-induced
      immobility period. The increase in immobility time was highest after 2 h of LPS
      administration. Desipramine (10 mg/kg), a tricycle antidepressant, or fluoxetine
      (10 mg/kg), a serotonin reuptake inhibitor, significantly reversed the LPS
      induced increase in immobility time. Cyclooxygenase inhibitors nimesulide (1, 2
      and 5 mg/kg), naproxen (10 mg/kg) and rofecoxib (2 mg/kg) did not alter the
      despair behavior per se. Nimesulide (10 mg/kg) did reverse reserpine-induced
      immobility. Nimesulide (2 mg/kg), naproxen (10 mg/kg) and rofecoxib (2 mg/kg)
      significantly reversed LPS-mediated despair behavior. The present study
      demonstrated that LPS-induced inflammatory responses in the brain may cause
      despair behavior. Reversal with a cyclooxygenase inhibitor indicates the role of
      prostaglandins in despair behavior.

PMID- 11838317
TI  - Characterizations of recombinant human tartrate-resistant acid phosphatase from
      osteosarcoma: comparison study between recombinant and placental proteins.
AB  - We cloned the human tartrate-resistant acid phosphatase (TRAP) gene from human
      osteosarcoma cells (Saos-2), and produced recombinant human TRAP (rhTRAP) using a
      baculovirus vector expression system. RhTRAP from Sf9 culture medium was purified
      by cation exchange chromatography, gel filtration and affinity chromatography.
      The molecular mass and amino acid composition of the rhTRAP were consistent with
      the deduced amino acid composition from the TRAP gene. The N-terminal amino acid
      sequence of rhTRAP was identical to that of TRAP purified from osteoclastoma and
      hairy cell leukemia spleen. The monoclonal antibodies generated against rhTRAP
      also reacted to human placental TRAP (pTRAP). The optimum pH of rhTRAP and pTRAP
      were pH 5.0-5.5 and pH 6.0-6.5, respectively. The enzymatic activities of rhTRAP
      and pTRAP were activated by reducing agents such as 2-mercaptoethanol,
      dithiothreitol and ascorbic acid. The activities of rhTRAP and pTRAP were
      enhanced by Fe2+ ions, but were inhibited by Fe3+ ions. The present results
      indicate that rhTRAP has similar properties to the native human TRAP, and suggest
      that the enhancement of TRAP activity by reducing agents might be expressed via
      the reduction of Fe ions at the metal center.

PMID- 11838319
TI  - Mild to severe lithium-induced nephropathy models and urine N-acetyl-beta-D
      glucosaminidase in rats.
AB  - Long-term treatment with lithium induces functional and/or structural
      disturbances in the kidneys. However, no procedure has been established for the
      early diagnosis of lithium intoxication. In this study, we prepared mild to
      severe lithium-induced nephropathy rat models and examined the usefulness of
      urine N-acetyl-beta-D-glucosaminidase (NAG) for the early diagnosis of lithium
      induced renal insufficiency. Lithium was administered by repeated intraperitoneal
      injection (1, 2 and 4 mEq/kg/day for 10 days). We also measured the plasma
      creatinine and paraaminohippuric acid (PAH) clearance, and observed renal
      histological changes. Lithium pretreatment elevated the plasma creatinine level
      and decreased PAH clearance in a dose-dependent manner. The NAG level in the
      lithium 4 mEq/kg group was very high. The levels in the lithium 1 mEq/kg and 2
      mEq/kg groups were almost the same and were higher than the control group. A
      histological examination of the kidney revealed glomerular congestion and/or
      atrophy and tubular expansion in all of the groups except the control group.
      These histological changes were dose-dependent. In conclusion, urine NAG may be
      useful in the early diagnosis of renal side effects caused by lithium therapy.
      When the urine NAG level becomes high in a patient taking lithium for bipolar
      disorder, the physician may need to consider lithium-induced renal insufficiency.

PMID- 11838320
TI  - Cardiovascular effects of the R- and S-enantiomers of ibutilide in conscious
      beagle dogs.
AB  - To support its class III antiarrhythmic candidacy, we examined the acute
      cardiovascular effects of ibutilide and its R- and S-enantiomers in conscious
      beagle dogs. Eight dogs were given stepped i.v. doses (0.01, 0.1, and 1.0 mg/kg)
      of these agents while monitoring changes in mean arterial pressure (MAP), heart
      rate (HR), and lead II ECG QTc length (index of class III activity). None of the
      treatments affected MAP and only R-ibutilide slightly increased HR. The R-isomer
      was also slightly more potent in prolonging QTc at the lowest dose, but its mean
      peak QTc change (+44 msec) overlapped those achieved with racemic (+37 msec) and
      S-ibutilide (+41 msec). Plasma drug analyses showed that total drug levels (sum
      of enantiomers) were similar with each agent, averaging 1, 12, and 170 ng/ml at
      30 min after the low, middle, and high doses, respectively. Nearly equal
      enantiomer proportions were seen after racemic ibutilide, and no chiral inversion
      was seen after enantiomer administration. All treatments were well tolerated
      without enhanced ventricular ectopy. These data demonstrate that in conscious
      dogs, racemic, R-, and S-ibutilide similarly prolong QTc independent of
      appreciable cardiovascular changes, differential pharmacokinetics, or
      dysrhythmias, thereby helping to establish racemic ibutilide as the optimal
      developmental candidate.

PMID- 11838321
TI  - Using models in cardiovascular research: report on the satellite meeting to the
      International Congress of Physiological Sciences, Models in Cardiovascular
      Research.
AB  - Humans have used animals for centuries to understand their own biology. From
      September 2-4, 2001, scientists from around the world converged on Brisbane, in
      Australia, to discuss the use of animal models in cardiovascular research at a
      satellite meeting to the 34th International Congress of Physiological Sciences
      (August 26-September 1, 2001, Christchurch, New Zealand). The appropriateness of
      each model to the human disease was a major consideration. Other themes were the
      use of models to understand pathological processes, and to determine potential
      new targets for pharmacological intervention.

PMID- 11838322
TI  - The role of aldose reductase inhibitors in diabetic complications: recent trends.
AB  - Pharmacological intervention of hyperglycemia-induced diabetic complications
      would be of great clinical significance since it is very difficult to maintain
      normoglycemia by any means in patients with diabetes mellitus. Several factors
      and pathways are involved in diabetic complications. One of the major
      contributory factors is aldose reductase. The beneficial effects of aldose
      reductase inhibitors in animal models have been reported. The clinical efficacy
      of these agents, however, is far from satisfactory and the reasons for this may
      vary. Recent advances in understanding the structure-based functioning,
      physiological and pathophysiological role of aldose reductase, the use of
      transgenic animal models and the abundant availability of human aldose reductase
      have greatly influenced the design and development of its inhibitors, which are
      highly selective, specific, potent and less toxic. Concurrently, other mechanisms
      involved in diabetic complications are being explored as targets for better
      therapeutic agents.

PMID- 11838323
TI  - Pathogenesis of diabetes: our current understanding.
AB  - Understanding the pathogenesis of any disease is of prime importance when
      considering treatment. Recent breakthroughs in the evaluation and management of
      diabetes and the availability of new therapeutic regimens make it imperative that
      the primary care physician be aware of these advances to improve patient care.
      This article discusses our current understanding of the pathogenesis of both type
      1 and type 2 diabetes mellitus. A glossary of pertinent genetic terms is
      included.

PMID- 11838325
TI  - Glycemic control in the prevention of diabetic complications.
AB  - The relationship between abnormal circulating glucose levels and the development
      of long-term diabetic complications became apparent soon after the introduction
      of insulin 70 years ago and the avoidance of early death due to ketoacidosis.
      Classic observational studies by Pirart described the relationship between
      increased glycosuria and the ultimate development of diabetic retinopathy,
      nephropathy, and neuropathy. Nonetheless, it required the findings of randomized,
      controlled clinical trials to finally and definitively establish the relationship
      between glucose control and microvascular diabetic complications. With the
      publication of the Diabetes Control and Complications Trial, the Kumomoto Trial,
      and the United Kingdom Prospective Diabetes Study, the impact of glycemic control
      in the development of microvascular complications was confirmed. Our
      understanding of the pathophysiology of diabetes--particularly, the dysmetabolic
      changes seen in type 2 diabetes--includes abnormalities in lipid metabolism, fuel
      flux, and endothelial function. Diabetes control, therefore, can no longer be
      viewed exclusively as glucose management. Rather, a more global approach is
      necessary to minimize risks of both microvascular and macrovascular
      complications. This article explores data supporting a variety of interventions
      that have been shown to reduce morbidity and mortality associated with long
      standing diabetes mellitus. In addition to acknowledging the relationship between
      complications and diabetic metabolic abnormalities, this article presents a
      health economics perspective by examining the cost-effectiveness and health
      utility of these interventions.

PMID- 11838324
TI  - Update on the cardiometabolic syndrome.
AB  - An array of metabolic, hemodynamic, and renal abnormalities constitutes the
      cardiometabolic syndrome. A hallmark of this syndrome is visceral obesity and
      associated insulin resistance/hyperinsulinemia. The syndrome is also associated
      with essential hypertension, abnormalities in the circadian rhythm of blood
      pressure and heart rate, the diabetic dyslipidemic syndrome, hypercoagulability,
      hyperuricemia, increased cardiovascular inflammation, and microalbuminuria, all
      of which contribute to an increased risk of cardiovascular disease morbidity and
      mortality. This article reviews current knowledge about the interrelationship of
      the various factors that make up the cardiometabolic syndrome and its
      implications for individuals with and without diabetes mellitus.

PMID- 11838326
TI  - Current therapeutic algorithms for type 2 diabetes.
AB  - Although type 2 diabetes is a heterogeneous disorder, there are certain
      management goals that are common to all patients. Tight metabolic control reduces
      the complication rates; therefore, for patients with type 2 diabetes, lowering
      the hemoglobin A1c toward normal is a major goal, as is the achievement of normal
      lipids and blood pressure. This article first discusses the standard regimens and
      agents available and then focuses on the newer approaches to reaching these
      goals.

PMID- 11838327
TI  - Insulin therapy: optimizing control in type 1 and type 2 diabetes.
AB  - Insulin has been available for therapeutic use for more than 75 years and remains
      a powerful pharmacologic tool with nearly unlimited potential to lower plasma
      glucose levels in patients with diabetes. Required essentially by all patients
      with type 1 diabetes and many patients with type 2 diabetes, insulin is capable
      of restoring near-normoglycemia--the primary treatment goal to forestall the
      onset and progression of long-term complications. Attainment and maintenance of
      near-normal glycemic control can be achieved with the use of insulin replacement
      strategies designed to simulate the physiologic, nondiabetic patterns of insulin
      secretion in response to 24-hour postabsorptive and postprandial glucose
      profiles. This article reviews the physiologic basis and current therapeutic
      agents for optimal insulin replacement and provides practical clinical guidelines
      and strategies to achieve near-normal glycemic control in patients with either
      type 1 or type 2 diabetes.

PMID- 11838328
TI  - Oxidant stress in cardiovascular disease: an emerging modality or a disproved
      theory?

PMID- 11838329
TI  - Low-density lipoprotein oxidation.
AB  - Free radical mediated oxidation of low-density lipoproteins (LDL), which has been
      extensively studied in the last two decades, plays a central role in the
      development of the atherosclerotic plaque. Oxidation involves the lipid moiety of
      LDL in a chain reaction mechanism. In the initial phase, free radicals
      preferentially attack highly oxidizable polyunsaturated fatty acids. Subsequent
      recruitment of other molecules includes cholesterol and phospholipids. The
      process of oxidation is counteracted by antioxidants present in LDL. By-products
      formed during oxidation of LDL lipids, which may have biological activity, react
      with amino acid residues of the LDL protein backbone with the consequent
      modification of chemical and immunological properties responsible for cellular
      receptor shift. Oxidation-altered apolipoprotein B of oxidized LDL is, in fact,
      recognized by the macrophage scavenger receptor responsible for foam cell
      formation. The mechanism of LDL oxidation and the impact on atherogenesis are
      discussed.

PMID- 11838330
TI  - Oxidized lipids.
AB  - The addition of oxygen to lipids, in response to inflammatory and mitogenic
      stimuli, is an important process developed by biological systems to generate a
      wide spectrum of compounds both by enzymatic and non-enzymatic mechanisms. These
      oxidized lipids may serve as messengers for communication both within and between
      cells or may induce structural and metabolic changes in the cell. Since chronic
      inflammation has been proposed as an important risk factor for coronary events by
      making atherosclerotic plaques prone to rupture, extensive studies have been
      conducted to probe the involvement of the different pathways of lipid oxidation
      in the pathogenesis of coronary heart disease. The oxidation of arachidonic acid
      and 2-arachidonylglycerol through the activity of cyclooxygenase-2 may play a
      role in plaque instability through dysregulation of vascular tone and induction
      of endothelial dysfunction. Moreover, two families of biologically active
      mediators formed by free-radical catalyzed oxidation of arachidonic acid and
      phosphatidylcholine, i.e. isoprostanes and platelet activating factor-like
      lipids, respectively, may be involved. Clarification of the metabolic steps of
      lipid oxidation altered in unstable coronary artery disease will be of valuable
      help in identifying new cardiovascular markers for the prediction of the long
      term risk of death from cardiac causes. The integration of this information with
      the presence of mutations in the genes encoding the enzymatic machinery of lipid
      oxidation will be useful in the selection of patients with increased risk of
      myocardial infarction.

PMID- 11838331
TI  - Vitamin E: murine studies versus clinical trials.
AB  - Vitamin E is the most effective lipid-soluble antioxidant present in mammalian
      cells. The hypothesis that links vitamin E to atherogenesis postulates that
      oxidative modifications of unsaturated fatty acids in the low-density lipoprotein
      particles play a crucial role in the pathogenesis of this chronic disease.
      Therefore, vitamin E supplementation should reduce the extent of oxidation and,
      thus, be protective against atherosclerosis. This hypothesis is strongly
      supported by studies in murine models of atherosclerosis. In contrast, clinical
      trials using this vitamin have been giving a more confused picture than expected,
      with results ranging from a significant protective action to the absence of any
      effect. However, these findings do not reduce the validity of the "oxidative
      hypothesis" and of the large body of experimental evidence accumulated so far in
      its favor. Several differences between animal studies and clinical trials, and
      among clinical trials themselves are taken into account in order to explain the
      conflicting findings. Finally, insights into what might be the most appropriate
      nature of future trials in humans are given.

PMID- 11838332
TI  - How to search for the predisposing role of psychological distress and its
      prevalence. Introduction.

PMID- 11838333
TI  - Epidemiologic perspective on the role of psychosocial factors.
AB  - The pathophysiology of acute myocardial infarction is complex and includes long
      term effects of risk factors leading to the formation of coronary
      atherosclerosis, intermediate-term effects of risk factors leading to plaque
      vulnerability, and short-term effects of triggers that precipitate the onset of
      acute myocardial infarction and other cardiovascular events. Psychosocial factors
      may play an etiologic role at each of these stages. The purpose of this brief
      paper is to identify opportunities and challenges that face the cardiology
      community over the next decade as we continue to evaluate the role of
      psychological stressors in the etiology of acute myocardial infarction and other
      acute cardiovascular events.

PMID- 11838335
TI  - Mental stress as a trigger of acute cardiac events: the role of laboratory
      studies.
AB  - Mental stress has long been implicated as a potential trigger of myocardial
      infarction and sudden cardiac death. This article reviews research conducted in
      the past two decades utilizing laboratory studies to investigate behaviorally
      induced pathophysiological effects (including increased cardiac demand, decreased
      myocardial supply, and impaired dilation of coronary resistance vessels), in
      patients with coronary artery disease. The clinical significance of mental stress
      induced ischemia is supported by findings of a predictive relationship of mental
      stress-induced ischemia for ambulatory ischemia and subsequent cardiac events.
      Mental stress-induced ventricular fibrillation, ventricular tachycardia, and T
      wave alternans are also being explored as possible markers of arrhythmic
      vulnerability in human and animal models. T-wave alternans comparable to exercise
      can be induced by an anger-like state in an animal model, and with mental stress
      in patients with implantable cardioverter-defibrillators. Future directions for
      research on mental stress and cardiac events are suggested, including further
      studies of mechanisms of mental stress-induced arrhythmia and ischemia,
      additional studies of the prognostic significance of stress-induced ischemia and
      T-wave alternans, and use of pharmacological and psychosocial treatments for
      preventing stress-induced cardiac events.

PMID- 11838334
TI  - Assessment and treatment of depression in coronary artery disease patients.
AB  - Depressive symptoms occur frequently among patients with coronary artery disease
      (CAD), with prevalence estimates ranging from 15 to 30%. Risk ratios for first
      and recurrent cardiac events related to depression are comparable to well
      established CAD risk factors and range from 2 to 7. The commonly atypical nature
      of depression in individuals with CAD plays an important role in the under
      diagnosis of depression in these patients. This review indicates that presence of
      atypical and subclinical depression, as well as of clinical major depressive
      disorders, significantly increase the risk of cardiac events. Pathophysiological
      mechanisms include altered autonomic nervous system activity, increased tendency
      toward blood coagulation, and elevated low-grade inflammation. Evidence suggests
      that depression in CAD patients does not reflect anatomical CAD severity or use
      of anti-ischemic medications. In addition to these pathophysiological pathways,
      depression affects CAD progression via adverse health behaviors such as smoking,
      poor compliance, and reduced exercise levels. Initial screening for depressive
      disorders can be accomplished using questionnaires, but structured clinical
      interview are preferred for definite diagnosis of depression. Optimal treatment
      of depression in CAD generally involves both psychological and pharmacological
      interventions that affect both depression and its biological correlates relevant
      to CAD progression.

PMID- 11838336
TI  - The use of robotic technology in the LAST operation.
AB  - BACKGROUND: The LAST operation represents a good option for single left anterior
      descending artery (LAD) revascularization. We report our preliminary experience
      with the LAST operation performed with the aid of the "da Vinci" Intuitive
      robotic system. METHODS: From January 2000 to May 2001, 12 patients (11 males and
      1 female, mean age 62 +/- 8 years) underwent the LAST operation. All patients had
      a proximal LAD lesion either not suitable for coronary angioplasty or
      unsuccessfully treated at coronary angioplasty previously. The mean preoperative
      ejection fraction was 55 +/- 5%. In all patients, left internal mammary artery
      (LIMA) harvesting was carried out endoscopically using robotic technology. After
      heparin administration the LIMA was distally divided to check the adequacy of the
      blood flow. An incision of about 6 cm was then made in the appropriate
      intercostal space and the LAD was exposed using a special costal retractor.
      Following the insertion of a temporary intracoronary shunt, the LIMA was
      anastomosed to the LAD. RESULTS: No hospital or delayed death occurred.
      Uneventful conversion to midline sternotomy was necessary in one patient who
      developed ischemic changes and hemodynamic instability. One patient had a
      revision for postoperative bleeding. All patients were discharged within the
      first postoperative week and in 4 of them optimal patency of the LIMA graft was
      angiographically documented. CONCLUSIONS: The use of robotic technology seems to
      overcome all the drawbacks associated with the LAST operation and enhances the
      role of minimally invasive surgery in coronary artery revascularization.

PMID- 11838337
TI  - Port-access cardiac surgery: clinical experience with first 50 cases.
AB  - BACKGROUND: Minimally invasive cardiac surgery constitutes an expanding field for
      the treatment of many cardiac diseases. We analyze our experience with the first
      50 patients operated upon using the port-access system. METHODS: From October
      1999 to October 2000, 50 patients underwent cardiac operations with the port
      access technique, for the correction of mitral and tricuspid disease, atrial
      septal defect closure, and removal of cardiac tumors. The mean age was 56.5
      years. In 23 patients the mitral valve was repaired, in 14 cases a prosthetic
      replacement was performed, in 2 patients a paravalvular leak was resutured, 1
      patient had a cardiac myxoma removed, and 1 patient had a correction of tricuspid
      regurgitation. In 9 cases an atrial septal defect closure was performed. RESULTS:
      One redo patient, with severe tricuspid regurgitation, needed conversion to
      sternotomy; in all the other cases the results of surgery were good and there
      were no surgical limitations. The mean cross-clamping time and bypass time were
      53 +/- 19 and 77 +/- 27 min respectively. The mean in-hospital stay was 6 days.
      Re-exploration for bleeding was required in 7 patients (14%). Three patients (6%)
      presented with a postoperative neurological lesion; 2 recovered completely within
      48 hours whereas 1 patient had permanent hemiplegia at discharge. There was one
      hospital death (an 81-year-old patient died of multiorgan failure on the
      thirteenth postoperative day). CONCLUSIONS: Minimally invasive port-access
      surgery is a reliable alternative to conventional surgery for the treatment of
      mitral and tricuspid disease, the removal of cardiac tumors, and the correction
      of atrial septal defects. It reduces trauma to the patient, provides a better
      cosmetic result and also allows for a faster recovery. Careful patient selection
      is important to avoid complications. Redo patients can be successfully treated
      and the risks of re-sternotomy avoided.

PMID- 11838338
TI  - The challenge of innovation.

PMID- 11838339
TI  - Right ventricular myocardial diastolic dysfunction in different kinds of cardiac
      hypertrophy: analysis by pulsed Doppler tissue imaging.
AB  - BACKGROUND: Right ventricular (RV) chamber involvement has been demonstrated in
      hypertrophic cardiomyopathy (HCM) as well as in hypertensive left ventricular
      hypertrophy (LVH) but little is known about RV myocardial dysfunction occurring
      in these two pathologies. The aim of this study was to compare Doppler tissue
      imaging (DTI) of the right ventricle in HCM and LVH in relation to DTI of the
      left ventricle and Doppler standard of the RV and left ventricular (LV) inflow.
      METHODS: Thirty controls, 20 hypertensives with LVH, and 23 patients with HCM
      involving the interventricular septum underwent Doppler echocardiography and
      pulsed DTI of the LV lateral mitral annulus and the RV lateral tricuspid annulus.
      RESULTS: Patients with HCM had a higher blood pressure, septal thickness and LV
      mass in comparison with the other two groups. The RV wall thickness did not
      differ between HCM and LVH. The fractional shortening, but not the tricuspid
      annular plane excursion, was higher in HCM. After adjusting for the mean blood
      pressure, the Doppler-derived global LV and RV diastolic functions were more
      impaired in HCM than in LVH. Also the majority of DTI LV and RV diastolic
      measurements were altered more in HCM. At the RV tricuspid annulus, myocardial
      diastolic indexes were impaired in HCM and LVH in comparison with controls but
      the deceleration and relaxation times distinguished also HCM and LVH, being much
      longer in HCM (p < 0.0001). In the overall population, the RV myocardial
      relaxation time was positively related to the septal wall thickness and the RV
      wall thickness, even after adjusting for age, heart rate, diastolic blood
      pressure, fractional shortening and DTI mitral relaxation time. CONCLUSIONS: The
      impairment of RV myocardial relaxation is much more evident in HCM than in LVH,
      its degree being independently associated with the extent of both the septal and
      RV wall thickness. Pulsed DTI may be useful to distinguish the extent of RV
      myocardial dysfunction in different types of cardiac hypertrophy.

PMID- 11838340
TI  - Transferring patients for direct coronary angioplasty: a retrospective analysis
      of 135 unselected patients with acute myocardial infarction.
AB  - BACKGROUND: Direct coronary angioplasty (PTCA) represents the most effective
      treatment for acute myocardial infarction. However, only a minority of patients
      are initially admitted to hospitals with direct PTCA facilities available 24
      hours daily. The safety and benefits of transfer direct PTCA are debated, and we
      have no data about the early return of patients to the admission hospital.
      METHODS: We report our experience with transfer direct PTCA in unselected
      patients with acute myocardial infarction, and the early post-procedural return
      to the referring hospitals. RESULTS: One hundred and thirty-five unselected
      patients with acute myocardial infarction were referred to our center for direct
      PTCA during 1998. The majority of patients (n = 93, 69%, group T) were initially
      admitted to a primary hospital whereas the rest (n = 42, 31%, group NT) were
      directly admitted to our hospital. One hundred and thirty-four patients underwent
      coronary angiography, and direct PTCA was attempted in 126 patients. The median
      time interval between admission and direct PTCA was higher in group T (60 vs 40
      min, p < 0.001). Only 3 patients (3.2%) had severe complications during transfer
      to our center: 1 patient with cardiogenic shock died, and 2 patients had
      ventricular fibrillation. The procedural and in-hospital outcomes of both groups
      were similar. The early post-procedural transfer to the referring hospital was
      possible in 88% of patients; no complications occurred during the transfer. The
      incidences of cardiac mortality at 6 months and at long-term follow-up were 3.4
      and 5.1% respectively. CONCLUSIONS: In our experience, interhospital transfer for
      direct PTCA in unselected patients with acute myocardial infarction is feasible
      and safe. The early return to the admission hospital is safe and does not
      negatively influence the in-hospital outcome.

PMID- 11838341
TI  - Usefulness of glycoprotein IIb/IIIa inhibitors in unstable angina due to small
      vessel disease.
AB  - We describe the role of abciximab in unstable angina due to small vessel disease
      in a 58-year-old patient who was submitted to percutaneous transluminal coronary
      angioplasty and stenting of an occluded venous graft.

PMID- 11838342
TI  - Conduction system in cardiac amyloidosis: two cases succumbed to cardiac arrest.
AB  - The present article reports the histological study of the conduction system in 2
      cases of cardiac amyloidosis. The discrepant anatomical and clinical evidence yet
      confirmed the need for accurate ECG controls in all cases. Indeed, while in the
      first case evident lesions of the conduction system were revealed by surface
      ECGs, the second case did not exhibit significant ECG abnormalities but the right
      atrium and the His bundle showed slight fibro-amyloid involvement, as potential
      forerunners of high-risk arrhythmias.

PMID- 11838343
TI  - Thrombocytopenia and purpura-like lesions associated with clopidogrel.
AB  - We report a case of moderate thrombocytopenia associated with purpura-like
      phenomenon (four ecchymoses) that occurred within 72 hours of clopidogrel
      initiation and resolved promptly with drug withdrawal. This 61-year-old patient
      previously experienced an adverse skin reaction to ticlopidine without changes in
      the platelet count and without any other laboratory abnormalities. Since the
      introduction of clopidogrel instead of ticlopidine for the prevention or
      treatment of several cardiovascular diseases, only 11 cases of thrombotic
      thrombocytopenic purpura among more than 3 million individuals treated with
      clopidogrel have been reported. Recently, a case of severe thrombocytopenia,
      without concomitant purpura-like lesions, during therapy with clopidogrel has
      been described. To our knowledge, this is the first case of thrombocytopenia
      associated with purpura-like lesions with no evidence of thrombotic
      thrombocytopenic purpura during clopidogrel treatment.

PMID- 11838344
TI  - Images in cardiovascular medicine. Three-dimensional reconstruction of pulmonary
      valve endocarditis.

PMID- 11838345
TI  - [Arrhythmia risk stratification in patients with heart failure. Foreword].
AB  - The challenge of preventing arrhythmic sudden death is one of the major issues of
      today's treatment of heart failure. To pursue this aim, an accurate selection of
      candidates for sudden death has to be routinely carried out, while a maximized
      and individualized drug treatment has to be extensively administered in all high
      risk selected patients. However, in clinical practice there is no agreement on
      the selection criteria of sudden death risk, particularly in patients with
      advanced heart failure. Furthermore, the real impact of each category of drugs in
      reducing the risk of sudden death in heart failure patients is still under
      debate. As far as non-pharmacological options are concerned, implantable
      cardioverter-defibrillators (ICD) have been demonstrated to be the most effective
      therapy in patients with prior cardiac arrest due to ventricular fibrillation or
      poorly tolerated ventricular tachycardia. Low left ventricular ejection fraction,
      unsustained ventricular tachycardia and inducibility at electrophysiological
      study also may identify high-risk patients requiring ICD implantation. However,
      such a stratification seems to be effective in ischemic more than in non-ischemic
      patients, while generally the primary prevention of sudden death is still
      restricted to a minority of patients. Biventricular pacing has been proven to be
      effective in optimizing left ventricular function in more than 50% of left bundle
      branch block and advanced heart failure patients, while further studies are
      needed to evaluate the real impact of cardiac resynchronization therapy on hard
      endpoints, such as survival and long-term clinical outcome. Therefore, the
      selection criteria of "responders" to this novel non-pharmacological therapy
      still have to be defined. There is convincing evidence in the literature that
      tailored drug therapy can be highly effective in preventing heart failure
      progression as well as in reducing total and sudden mortality. Nevertheless,
      prevention of sudden death is still a debated point in heart failure treatment.
      For this reason, we aimed to provide heart failure specialists with updated
      reviews on this topic, such as those published in this issue of the Italian Heart
      Journal Supplement. Therefore, we are proud to present all the authors who
      contributed with the high quality of their articles to this editorial effort.
      Obviously, we have to thank the authors, but we also have to address the readers,
      thanking them in advance for their interest in such an initiative.

PMID- 11838346
TI  - [Arrhythmia risk stratification based on etiological and anatomo-structural
      factors].
AB  - In patients with heart failure, sudden death is very common, particularly in
      subjects in NYHA functional class II and III (respectively 50-80% and 30-50% of
      all deaths). The mechanisms at the root of sudden death depend on whether heart
      failure is secondary to an ischemic or non-ischemic heart disease. In ischemic
      heart disease, sudden death is mainly arrhythmic (ventricular
      tachycardia/ventricular fibrillation caused by the reentry circuits in the
      infarct area or by acute ischemic episodes or bradyarrhythmia). In non-ischemic
      heart disease, the percentage of arrhythmic sudden deaths seems to be lower.
      Furthermore, a percentage of sudden death cases with heart failure can be linked
      to electromechanical dissociation and to pulmonary or systemic embolism. Moreover
      the risk stratification level differs depending on whether heart failure is
      caused by an ischemic or a non-ischemic heart disease. The various non-invasive
      studies mainly employed in patients with ischemic heart disease cannot be
      reliably used to study patients with non-ischemic heart disease. Even the
      programmed ventricular stimulation demonstrated prognostic reliability only in
      cases involving ischemic heart disease. The therapeutic approach may also be
      conditioned by the heart disease responsible for heart failure. To date, for
      example, all the studies published on primary prevention of sudden death with an
      implantable defibrillator have been carried out in patients with ischemic heart
      disease.

PMID- 11838347
TI  - [Arrhythmia risk stratification based on clinical and functional data].
AB  - The term "sudden death" indicates a natural and rapid death, an unexpected event
      in patients with high mortality rates such as those with heart failure. Sudden
      death in patients with heart failure is responsible for some of 40% of all
      deaths. A detailed clinical evaluation in patients with heart failure is
      extremely helpful for risk stratification. Although sex has been shown to have no
      prognostic relevance, heart failure due to coronary artery disease is associated
      with a higher mortality rate when compared to other etiologies. Left ventricular
      ejection fraction is the independent risk factor with the highest predictive
      value of survival. However, in patients with heart failure, except for the
      advanced stages, sudden death shows an incidence comparable with that of
      progressive pump failure. Like left ventricular ejection fraction, even the
      functional classifications of heart failure (such as NYHA) are to be considered
      as a non-specific marker of overall mortality. In fact, despite the close
      relation between advanced disease stages and a higher mortality rate, a large
      overlap has been demonstrated for the intermediate classes. The noninvasive
      assessment of oxygen consumption during cardiopulmonary exercise testing has been
      recognized as an independent risk factor and patients with a peak oxygen
      consumption < 10 ml/kg/min should be recommended for cardiac transplantation. In
      these patients no clear relation with an increased risk of sudden death has been
      demonstrated. In conclusion, the commonly employed clinical-functional indexes
      (left ventricular ejection fraction, functional classifications, peak oxygen
      consumption during cardiopulmonary testing) are significant predictors of overall
      mortality, however they are useless in the risk stratification for death due to
      fatal arrhythmias.

PMID- 11838348
TI  - [Arrhythmia risk stratification in patients with heart failure according to drug
      treatment and its effects].
AB  - Despite therapeutic advances in heart failure treatment, this syndrome still
      presents a poor prognosis, with a relevant mortality due to both systolic
      dysfunction progression and sudden death. Sudden cardiac death appears to be
      relatively more frequent in less compromised patients (NYHA functional class I)
      but in absolute numbers it is more frequent in more functionally compromised
      patients. The ability to predict sudden cardiac events with current available
      tests is poor, with the possible exception of electrophysiological test in
      ischemic cardiomyopathy. The risk of sudden death is proven to be increased in
      more advanced cardiac dysfunction and frequently the acute event can be
      precipitated by ischemia. Therefore the best approach in the prevention of sudden
      cardiac death may well be the proper treatment of ischemia and cardiac
      dysfunction. Beta-blockers have demonstrated a favorable effect in the prevention
      of sudden cardiac death. ACE-inhibitors can significantly reduce global death in
      heart failure patients, but their impact on sudden death appears to be limited.
      The same may be true for angiotensin II blockers. Diuretics have generally been
      demonstrated to increase sudden death, possibly via electrolyte imbalance; this
      may explain why spironolactone has a pronounced impact in reducing sudden death.
      Inotropes, in spite of their good effect on refractory heart failure and their
      usefulness in the compassionate care of terminally ill heart failure patients,
      have demonstrated an increase in sudden cardiac death. The same holds true for
      digoxin, in spite of its ability to reduce death due to heart failure
      deterioration. Antiarrhythmic drugs, with the possible exception of amiodarone,
      have demonstrated an unfavorable effect on sudden death incidence.

PMID- 11838349
TI  - [Arrhythmia risk stratification in patients with heart failure: prognostic
      evaluation of arrhythmia risk].
AB  - Sudden cardiac death is one of the more frequent causes of death in patients with
      heart failure. Thus, identification of patients at risk is a major clinical
      problem not only for the unpredictability of the event but also for the
      continuous growth of patients' number. The most widely used parameter for risk
      stratification is ejection fraction. Unfortunately, its predictive accuracy is
      limited and often it is impossible to distinguish patients with an increased
      arrhythmic mortality from those with an increased mortality due to pump failure.
      Heart rate variability and baroreflex sensitivity analysis has been largely
      utilized to obtain information on autonomic modulation of sinus node as well as
      to identify patients at risk. However, at variance with results observed in post
      myocardial infarction patients, lower values of both parameters have been
      reported in patients with either an increased total or arrhythmic mortality. More
      recently, T wave alternans analysis has been found effective in identifying
      patients with an increased arrhythmic risk. Ongoing studies will provide evidence
      to support the use of this non-invasive technique in patients with cardiac
      insufficiency. Finally, the role of programmed electrical stimulation in heart
      failure patients appears limited. Inducibility of monomorphic sustained
      ventricular tachycardia seems to correlate better with the presenting clinical
      arrhythmia than with patient outcome. In conclusion, our capability of
      identifying heart failure patients at risk for arrhythmic death is far from being
      satisfactory. It is possible that the combination of results of multiple non
      invasive tests such as reduction in ejection fraction and positivity for T wave
      alternans may not only provide general prognostic information but also facilitate
      the appropriate identification of patients at risk who may benefit from
      antiarrhythmic therapy.

PMID- 11838350
TI  - [Prognostic value of ventricular arrhythmias].
AB  - In patients with heart failure ventricular arrhythmias correlate with the
      functional class and thus they are a marker of heart disease severity. An
      "independent" prognostic value of ventricular arrhythmias is generally accepted
      in post-infarction patients, but it is controversial in the presence of other
      heart diseases. According to the results of the MADIT and MUSTT studies the
      prognostic significance can be improved in post-infarction patients with non
      sustained ventricular tachycardia during an electrophysiologic study aimed to
      evaluate the inducibility of sustained ventricular tachyarrhythmias with
      programmed electrical stimulation: in the "non-inducible" patients the prognosis
      is better than in "inducible" patients. Thus, we suggest to perform an
      electrophysiological evaluation in post-infarction patients and in patients with
      non-sustained ventricular tachycardia.

PMID- 11838351
TI  - [Prognostic value of supraventricular arrhythmias in heart failure].
AB  - Supraventricular tachyarrhythmias can be responsible for severe hemodynamic
      derangement which may contribute to the progression and worsening of heart
      failure. The resultant effect of these arrhythmias, however, is conditioned by
      several concomitant factors, such as age of the patients, left ventricular
      systolic function, and ventricular rate response. If the role of such arrhythmias
      in functional class, morbidity, and functional capacity is well accepted,
      controversial data are available on their role on mortality in patients with
      heart failure.

PMID- 11838352
TI  - [Variables of arrhythmia risk in relation to pacemaker and implantable
      defibrillator].
AB  - Patients suffering from heart failure are at high risk of arrhythmic death.
      Conventional pacemakers have not shown to affect mortality in patients with
      chronic heart failure and sick sinus syndrome, while this issue is established in
      patients with III degree or advanced atrioventricular block. Biventricular pacing
      has recently been introduced in clinical practice and the experience is limited;
      to date, only an improvement in symptoms and quality of life has been shown.
      Biventricular pacing with implantable cardioverter-defibrillator back-up is
      promising. The implantable cardioverter-defibrillator is able to reduce total and
      sudden mortality in high risk patients, as clearly demonstrated by several
      randomized clinical trials.

PMID- 11838353
TI  - [Indications and potential benefits of implantable automatic defibrillator
      endowed with biventricular pacing].
AB  - Heart failure (HF) is associated with a poor long-term survival due to
      progressive refractory heart dysfunction and sudden cardiac death. Cardiac
      resynchronization through three-chambered atriobiventricular pacing has been
      introduced to treat patients with drug-refractory HF and unsynchronized
      ventricular activation due to left bundle branch block (LBBB). The technique is
      aimed to overcome inter- and intraventricular conduction delays leading to a
      ventricular dyssynchrony, characterized by paradoxical septal wall motion,
      presystolic mitral regurgitation, and reduction in diastolic filling times. Acute
      studies demonstrated that biventricular pacing (and maybe left ventricular pacing
      alone) may improve both systolic and diastolic function. First studies on
      chronically paced patients consistently showed that the QRS shortening was
      associated with a significant improvement in symptoms, NYHA functional class,
      left ventricular ejection fraction (LVEF), exercise tolerance, and quality of
      life. As far as sudden cardiac death prevention in HF is concerned, the
      implantable cardioverter-defibrillator (ICD) has been demonstrated to be the most
      effective therapy in patients with prior cardiac arrest due to ventricular
      fibrillation or poorly tolerated ventricular tachycardia. Low LVEF, unsustained
      ventricular tachycardia and inducibility at electrophysiological study also may
      identify high risk patients requiring ICD implantation. Further studies are
      needed in evaluating the impact of cardiac resynchronization on hard endpoints,
      such as survival and long-term clinical outcome, as well as in upgrading risk
      stratification criteria to be used in candidate selection to ICD implantation.
      However, HF patients with prior cardiac arrest and LBBB should be considered as
      the optimal candidates to the "ICD implantation combined with biventricular
      pacing". Conversely, HF patients with LBBB, but without cardiac arrest, could be
      considered for "biventricular pacing combined with an ICD". The selection
      criteria for this novel non-pharmacological therapy still have to be defined. The
      authors emphasize the main indication to ICD implantation combined with
      biventricular pacing, i.e. HF patients with prior cardiac arrest and LBBB;
      controversially, while they discuss the other indications to biventricular pacing
      combined with an ICD.

PMID- 11838355
TI  - [Tolerability and clinical effects of carvedilol in patients over 70 years of age
      with chronic heart failure due to left ventricular dysfunction].
AB  - BACKGROUND: A number of studies showed the improvement in left ventricular (LV)
      function and clinical outcome that carvedilol produces in patients with severe
      congestive heart failure (CHF). However, no data are available regarding beta
      blocker treatment in older patients with CHF. The purpose of this study was to
      assess the tolerability and efficacy of carvedilol in patients > 70 years with
      CHF associated with LV systolic dysfunction. METHODS: Thirty-seven patients in
      NYHA functional class III-IV with LV ejection fraction < 45% and a mean age of 76
      +/- 6 years were prospectively studied. They received carvedilol which was
      associated with conventional therapy for CHF (ACE-inhibitors + diuretics +
      digitalis). The changes over time in clinical and echocardiographic variables
      (evaluated at baseline and every 6 months) were compared with those of 23
      patients treated with the sole conventional therapy. RESULTS: During a follow-up
      of 13 +/- 8 months, 5 patients interrupted carvedilol due to side effects
      (tolerability 87%). Among the 32 remaining patients, 8 died. NYHA functional
      class improved in the 56% of survivors, LV ejection fraction increased (30 to
      42%, p = 0.0002), mitral regurgitation and pulmonary capillary wedge pressure
      markedly decreased (2.0 to 1.0, p = 0.0001, and 19 to 13 mmHg, p = 0.0004,
      respectively). None of these variables was changed at the end of follow-up in the
      control group. Mortality was similar between the carvedilol (25%) and control
      group (22%). CONCLUSIONS: In the very elderly patients with LV systolic
      dysfunction and CHF carvedilol is well tolerated and safe. The addition of this
      drug to conventional therapy for CHF provides an important improvement in
      functional class, LV function and hemodynamics.

PMID- 11838354
TI  - [Efficacy and safety of ambulatory electric cardioversion of atrial fibrillation
      with monophasic and biphasic shock].
AB  - BACKGROUND: The aim of this study was to evaluate the safety and efficacy of
      ambulatory external cardioversion (EC) by means of monophasic and biphasic shock
      in patients with persistent atrial fibrillation (AF). METHODS: One hundred and
      twenty-seven consecutive patients with AF were submitted to EC, preceded by short
      general anesthesia with propofol, after pretreatment with oral anticoagulants for
      at least 3 weeks and, if not contraindicated, with amiodarone. In 87 of these
      patients we used monophasic shock and in 40 patients we used biphasic shock. Our
      protocol provided for up to 3 shocks delivered at an energy level ranging between
      200 and 360 J for monophasic and from 70 to 175 J for biphasic shock. The
      patients were discharged after 4 hours of ECG monitoring and following a
      determination of serum CK-MB at the fourth hour. RESULTS: The mean age of the
      patients submitted to EC with monophasic and biphasic shock (65 +/- 9 vs 67 +/- 7
      years) and the duration of AF (34 +/- 22 vs 32 +/- 25 days) were similar. The
      efficacy of EC with monophasic shock was 85% and the mean energy delivered was
      266 +/- 81.5 J. The efficacy of the EC with biphasic shock was 98% and the mean
      energy delivered was 127 +/- 40 J. The difference between the percentage of
      efficacy and the number of joules delivered was statistically significant (p <
      0.05). The mean value of the CK-MB after 4 hours following delivery of the shock
      was not significantly different: 2.5 ng/ml for monophasic vs 1.7 ng/ml for
      biphasic shock (p = NS). CONCLUSIONS: In our patients, ambulatory EC of
      persistent AF is safe and feasible; biphasic shock is more efficacious and
      requires less energy with respect to monophasic shock.

PMID- 11838357
TI  - [Exercise test after acute myocardial infarction: without therapy?].
AB  - In this article we analyze the role of ECG exercise test in the clinical
      evaluation and prognostic stratification of patients after acute myocardial
      infarction. Moreover, we analyze if test results may be influenced by drugs. In
      clinical practice, most of the cardiologists working in hospital perform pre
      discharge tests while patients are on medical therapy; after the acute event,
      exercise test is performed after pharmacological wash-out. In the thrombolytic
      age exercise test has a well-defined role in the evaluation and prognostic
      stratification of postinfarction patients, but some aspects regarding the way of
      performance and the opportunity of a pharmacological wash-out need further
      investigation.

PMID- 11838356
TI  - [Exercise test after acute myocardial infarction: on medical therapy?].
AB  - Given the great relevance of beta-blockers after myocardial infarction, we
      focused our attention on this therapy, considering also the difficulty of its
      management: it takes a long time to up titrate as well as to wash out. Other anti
      ischemic therapies, i.e. nitroderivatives and calcium-antagonists, are easier to
      manage and there is less need of precise schedules. Our belief is that
      predischarge exercise testing should be performed on beta-blocker therapy, since
      we deem unadvisable to interrupt this treatment in the early phase of the
      postinfarction clinical course, and the reasons are detailed in the text. After
      myocardial infarction, beta-blockers may reduce the sensitivity of predischarge
      exercise testing for the diagnosis of inducible ischemia; however, their
      interference does not seem to affect negatively the prognostic stratification of
      the test, also in the "thrombolytic era". This may be true since beta-blockers
      hide, but also cure, those forms of inducible ischemia of lower clinical
      importance, and only inducible ischemia occurring in spite of such therapy might
      be dangerous and should be treated with myocardial revascularization. Patients
      receiving thrombolytic treatment are a selected minority at lower clinical risk;
      it is necessary to emphasize that predischarge exercise testing is more
      frequently positive in these patients, probably because of the presence of
      residual stenosis of the infarct-related vessel that may often have a trivial
      relevance. The test has a lower negative predictive value in these patients,
      mainly for the higher incidence of reinfarction and ischemic events related to
      plaque instability, events that none of the provocative tests can predict
      accurately.

PMID- 11838358
TI  - [Comments on the guidelines of the European Society of Cardiology Task Force on
      pulmonary embolism].

PMID- 11838359
TI  - [Role of D-dimer test in excluding pulmonary embolism in patients with suspected
      pulmonary embolism in an Emergency Department].

PMID- 11838360
TI  - [Bolus fibrinolytic therapy in acute myocardial infarction].

PMID- 11838361
TI  - [Effect of sympathetic reinnervation on cardiac function after heart
      transplantation].

PMID- 11838362
TI  - [One or two mammary arteries for surgical revascularization of the myocardium?].

PMID- 11838363
TI  - What 2nd year medical students at the University of Mississippi Medical Center
      know about disease prevention.

PMID- 11838364
TI  - Looking back: the beginning of indigestion. Transactions of the MSMA, 1905, pages
      125-128..

PMID- 11838365
TI  - Emphasis on the heart.

PMID- 11838366
TI  - Progress seen in quality indicators.

PMID- 11838367
TI  - [A search for chromosome 13 QTL in a complex pig family].
AB  - A search for chromosome 13 QTL was carried out in a pig family of complex
      pedigree. The results indicated that a significant QTL on chromosome 13 was
      segregating in pig family. The QTL significantly affected body weight and average
      daily gain (P < 0.05), but the effect on backfat thickness was not significant (P
      > 0.05). Interval mapping localized this QTL between SW1898 and SW398. The
      estimated linkage position of this QTL was 75.2 cM. The QTL variance estimated at
      the marker interval was 0.9037 for the body weight and 0.0010 for average daily
      gain, respectively. This was the region which flanked the PIT1 gene, an essential
      transcriptional regulatory factor of growth hormone, prolactin and thyrotropin
      beta subunit. The present result confirmed a previous suggestion of a QTL for
      early growth traits at the estimated PIT1 position, and further implied that the
      effect of PIT1 genes on growth and body weight remained for the whole period of
      individual growth and development. Aditional evidence was also found which
      suggested a backfat QTL on chromosome 13, at a location approximately 28.3-63.4
      cM apart from the one for body weight and growth, but the level of significance
      was not consistent in different generations.

PMID- 11838368
TI  - [Research on genetic variation of heart fatty acid-binding protein gene in ten
      pig breeds].
AB  - The genetic variation of heart fatty acid-binding protein (H-FABP) gene in 561
      pigs including Duroc, Landrace, Large Yorkshire, Nanchang white pig, Erhualian,
      Meishan, Yushan black pig, Leping spotted pig, Jinhua black head-hind pig and
      Shanggao black head-hind pig were detected by PCR-RFLP with Hinf I, Hae III and
      Msp I. The results showed as follows: (1) Nanchang white pig presented only HH
      genotype while other breeds varied at the Hinf I-RFLP site; (2) The exotic breeds
      including Duroc, Landrace, Large Yorkshire and the native breed Nanchang white
      pig were proved to be polymorphic while the five Chinese local breeds presented
      no variation at the Hae III-RFLP site; (3) Among the tested breeds only Duroc
      presented variation at the Msp I-RFLP site. It is noted that all the Chinese
      local breeds present as AADD--genotypes.

PMID- 11838369
TI  - [Construction of linkage map of chromosomes 1 and 3 in large white x Meishan
      reference family].
AB  - A three-generation family of pigs has been constructed by using three Large White
      boars and seven sows of Meishan pigs as parents. In this family, five F1 males
      and twenty-three F1 females were intercrossed to generate 147 F2 offspring.
      According to the pig linkage map of USDA-MARC, eight and nine microsatellite
      markers selected on chromosomes 1 and 3 were chosen to span the entire
      chromosomes. The members of this family were genotyped. The characterization of
      these microsatellites was shown that they were polymorphic and could be used to
      construct linkage map and detect quantitative trait loci (QTLs). Linkage analyses
      were performed using the CRI-MAP software package. The lengths of the sex
      averaged linkage map were 182.3 cM and 180.2 cM on chromosomes 1 and 3,
      respectively. There were some differences between the linkage maps in this study
      and of USDA-MARC. The linkage map of chromosome 1 in female was found to be
      shorter than in male, and the contrary was on chromosome 3.

PMID- 11838370
TI  - [p16INK4a exon 1 alpha knockout in mouse embryonic stem cells].
AB  - INK4a/ARF locus distinguishes itself by its unusual structure and function. It
      contains 2 overlapping genes with exons 1 alpha, 2 and 3 encoding p16INK4a and
      exons 1 beta, 2 and 3 encoding p19ARF. Mice with their exons 2 and 3 of the
      INK4a/ARF knocked out are viable and fertile but develop spontaneous tumors at an
      early age and highly sensitive to carcinogenic treatment. However, mice with
      their exon 1 beta knocked out, without interference the expression of p16INK4a,
      show almost the same phenotype as those with their exons 2 and 3 knocked out.
      This raises a question of whether the mouse p16INK4a plays a role in tumor
      suppression. To investigate this problem, a targeting vector pointing to p16INK4a
      exon 1 alpha with 1.5 kb Eco81 I/Acc II fragment as short arm and 5.9 kb Xba
      I/Xho I fragment as long arm was built. After linearlization and purification,
      the targeting vector was introduced into ES cells through electroporation. Thirty
      seven G418- and gancyclovir-resistant colonies were picked out and one of them
      was confirmed as positive by Southern hybridization.

PMID- 11838371
TI  - [Influence of exogenous RNA upon expression of mouse albumin gene and its
      sensitivity to DNase I].
AB  - Cultured mouse fibroblasts were treated with rabbit liver RNA. Rat liver RNA was
      injected into mouse prostates. Influence of exogenous RNA upon expression of
      mouse albumin gene was detected by immunohistochemical staining. Nucleuses of
      cultured mouse fibroblasts treated with different RNAs were isolated and digested
      with DNase I. Mouse albumin gene was amplified by PCR to detect levels of its
      digestion. It was found that exogenous RNAs could increase the sensitivity of
      mouse albumin gene to DNase I digestion and promote its expression.

PMID- 11838372
TI  - [Single nucleotide polymorphism analysis in chicken insulin-like growth factor-II
      gene and its associations with growth and carcass traits].
AB  - In this experiment, F2 chicken derived from Broilers crossing with Silky was used
      to study the effect of insulin-like growth factor-II gene on growth and carcass
      traits. The partial gene was amplified by two pairs of primers, and single
      nucleotide polymorphism (SNPs) was detected by the technique of restriction
      fragment length polymorphism (RFLP), and then confirmed by DNA sequencing. The
      mutation was found in the exon-2 of the gene, and can be clarified by cutting of
      restriction enzyme Aci-I. The result of least square analysis showed the gene was
      significantly related with growth and carcass traits. It implied that the insulin
      like growth factor-II gene could be a genetic locus or linked to a major gene
      affecting greatly the growth and carcass traits in chicken.

PMID- 11838373
TI  - [The use of RNAi as a technique to study the functions of heart-related genes in
      Drosophila].
AB  - RNAi is a recently developed method to block the activity of cellular genes by
      artificially providing sense and anti-sense RNA corresponding to a target gene.
      By inducing rapid degradation of the corresponding endogenous mRNA and blocking
      new mRNA synthesis, RNAi leads to post-transcriptional gene silencing. Now this
      phenomenon has been claimed to exist in C. elegans, Drosophila, buds, fungi and
      plants and is being used to study the functions of some special genes or the
      known genes at specific time point. It is extremely useful for those genes or
      organisms that their mutants are not easily obtained. The Drosophila heart
      related genes, tinman and wingless, have been shown to play an important role in
      coordinating the early formation of heart progenitor cells and precursors, yet
      the late function is still unexplored. In this experiment, we took the advantage
      of RNAi technique, microinjected tinman and wingless dsRNA into the early embryos
      in Drosophila respectively and got these two genes' RNAi phenotypes, which were
      very similar to that of their mutant, showing heart tube defects or no heart
      precursors formation. tinman dsRNA even caused visceral mesoderm defects and the
      somatic muscles disruption, yet wingless dsRNA only affected heart precursors and
      had no effect on visceral mesoderm and somatic muscles, indication that the heart
      related genes dsRNA interference worked effectively and exclusively in
      Drosophila.

PMID- 11838374
TI  - [Molecular phylogeny of Drosophila auraria species complex].
AB  - Drosophila auraria species complex consists of five sibling species D. auraria,
      D. biauraria, D. triauraria, D. quadraria and D. subauraria. The complete
      sequences of nuclear ITS1 (internal transcribed specer 1) and mitochondrial CO II
      (Cytochrome Oxdase II), and partial sequences of nuclear Adh (alcohol
      dehydrogenase) of these five sibling species and their closely-related species,
      D. rufa, were determined. Using D. rufa, D. melanogaster and D. yukuba as
      outgroups, both most-parsimony (MP) and neighbor-joining (NJ) trees were
      constructed based on the sequences of each genetic marker. In each tree, D.
      subauraria always branched off first within Drosophila auraria species complex.
      Combined sequences of ITS1, Adh and CO II are 2327 bp (excluding gaps), of which
      255 sites are parsimony informative. Phylogenetic analyses based on the combined
      data sets can resolve the phylogenetic relationships of the five sibling species
      relatively well. According to the MP and NJ trees based on the combined
      sequences, D. subauraria was the first to emerge within Drosophila auraria
      species complex, thereafter D. biauraria branched off, D. auraria, D. triauraria
      and D. quadraria had a relatively recent speciation history. In this paper we
      propose a hypothesis about divergence events in Drosophila auraria species
      complex: The ancestor of this species complex diverged with D. rufa in warm
      temperate regions about 2.33 myr ago, then they invaded into cold-temperate
      regions. In cold-temperate regions, D. subauraria was firstly derived from the
      ancestor of Drosophila auraria species complex about 0.88 myr ago, thereafter D.
      biauraria emerged about 0.31 myr ago. During the process the ancestor reinvading
      into warm-temperate and subtropical regions, speciations of D. auraria, D.
      triauraria and D. quadraria were gradually completed. This hypothesis does not
      agree on the previous opinion that D. quadraria was the ancestral species of
      Drosophila auraria species complex.

PMID- 11838375
TI  - [QTL analysis of sheath blight resistance in rice (Oryza sativa L.)].
AB  - In this study, an indica variety Zhai Ye Qing 8 (ZYQ8) and a japonica variety
      Jing Xi 17(JX17) and their double haploid (DH) population were used. Sheath
      blight resistance of the DH population and their parents was investigated using a
      syringe inoculation method. Quantitative trait loci (QTL) analysis was undertaken
      based on a constructed molecular linkage map of this population in Hangzhou and
      Hainandao respectively. A total of four sheath blight resistant QTLs (qSBR-2,
      qSBR-3, qSBR-7 and qSBR-11) were identified, and located on chromosome 2, 3, 7
      and 11, respectively. Resistant alleles of qSBR-2, qSBR-3, and qSBR-7 were
      derived from the resistant parent ZYQ8, whereas resistant allele of qSBR-11 from
      susceptible parent JX17. qSBR-2, qSBR-3 and qSBR-7 were detected both in Hangzhou
      and Hainandao, whereas qSBR-11 was detected only in Hangzhou. Sheath blight
      response was significantly correlated with culm length and heading date in
      Hangzhou's test. Among the QTLs for culm length and heading date, only qCL-3 for
      culm length, was in the same chromosome region of qSBR-3, the other QTLs were not
      linked to the QTLs for sheath blight resistance.

PMID- 11838376
TI  - [Developmental genetic analysis for transparency of rice (Oryza sativa L.) at
      different environments].
AB  - The developmental behavior of gene expression for transparency of rice (TR) was
      analyzed from two-year experimental data at different filling stages by using
      both conditional and unconditional analysis methods for quantitative traits of
      seeds in cereal crops. It was revealed that the gene expression was most active
      for the performance of TR at the middle and late filling stages (8-21 d after
      flowering). The differences of expression at different environments for triploid
      endosperm nuclear genes, cytoplasmic genes and diploid maternal plant nuclear
      genes were found for the performance of TR. The phenomena of which some genetic
      effects were spasmodically expressible were detected among filling stages of
      rice. Because of the higher additive and cytoplasmic effects along with their
      interaction effects for TR at the filling stages, the better improving effects
      for this trait could be expected by selection in rice breeding. Some parents such
      as Zhenan 3 and 1391 were better than others for improving TR.

PMID- 11838377
TI  - [PCR walking in cotton genome using YADE method].
AB  - A Y-shaped adaptor dependent extension (YADE) method was developed to amplify the
      unknown genomic sequences adjacent to a known sequence, with the single-primer
      amplification completely suppressed. Using this method, two fragments, F027S and
      F027A, adjacent to a cotton ovule cDNA fragment (F027), were amplified using
      genomic DNA. It was demonstrated that F027S and F027A had 104 bp and 175 bp
      overlapped to F027, and contained 1 and 3 putative introns, respectively, all of
      which included conserved border sequence GT-AG and a putative branch site. The
      possible improvements and applications of YADE method are further discussed.

PMID- 11838378
TI  - [Identification and genetic study of major genes of resistance to Cerospora
      Sojina Hara in soybean].
AB  - Soybean frogeye leaf spot is one of the main diseases in Heilongjiang province.
      Usually, under several physical races of Cerospora Sojina Hara existed condition,
      the inheritance of resistance to this disease is controlled by equal-effect
      polygene. While high resistant parent 'Dongnong 9674 and other sensitive parents
      were used to make the three resistance-sensitive combinations in this paper, the
      resistance to Cerospora Sojina Hara had appeared the significant major gene
      effect. When P1, P2, F1, F2, B1, and B2 six generations were used to study and
      estimate the gene effects, major genes of resistance to Cerospora Sojina Hara
      were identified and the genetic parameters were also estimated in three
      combinations. The inheritance of genes resistant to this disease was fitted to
      the major gene and polygene mixed inheritance model or two gene loci inheritance
      model. The estimation of genetic parameters indicated that the additive,
      dominance and epistasis effects were existed and played an important role in the
      resistance to Cerospora Sojina Hara. It is meaningful in soybean resistance
      breeding to frogeye leaf spot.

PMID- 11838379
TI  - [Molecular cloning of specific porcine adipocyte membrane protein cDNA].
AB  - Specific porcine adipocyte membrane protein (PAMP), which was recently reported,
      is probably associated with the growth and development of adipocyte and regulator
      of adipose tissue. Using RT-PCR and RACE methods, and primer designed according
      to published sequence of PAMP gene 5' end, we have successfully amplified about a
      500 bp and a 400 bp from pig adipose tissue. A 500 bp fragment was retrieved,
      cloned and sequenced. The sequencing result showed that we have got the clone and
      sequence of cDNA 5'-end for PAMP gene.

PMID- 11838380
TI  - [The allozyme analysis of the genetic differentiation in self-inbred early
      generations of Lilium formolongi Hort].
AB  - The genetic diversity and differentiation of Lilium formolongi Hort. lines in
      self-inbred early generations were studied by allozyme electrophoresis. The
      results showed that mean allele number/locus, percentage of polymorphic loci,
      average observed heterozygosity and average expected heterozygosity were
      decreased with the increment of self-inbred generations. The purified loci,
      purified speed, fixed alleles and increment of genetic differentiation were
      different among lines because of selection and self-inbred. The mean genetic
      distances among F4 lines were larger than that of F3 lines, serving as another
      evidence to prove the differentiation among lines.

PMID- 11838381
TI  - [Gene cloning and expression of CTLA-4 in Streptomyces lividans].
AB  - Gene cloning and expression of CTLA-4 was performed in S. lividans with two new
      types of different signal peptides--vsi and gpp to investigate the secretory
      expression efficiency of CTLA-4. The hsCTLA-4 gene was fused to the vsi sequences
      and then inserted into the shuttle vector-pUWL-219. At the same time, the hsCTLA
      4 was inserted into the downstream of gpp signal peptide in the plasmid pLNSP.
      Then the recombinant plasmids were transformed into S. lividans TK24
      respectively. The two engineering strains were named as S. lividans [pUWL219-VC]
      and S. lividans [pLNSP/CTLA-4]. The result of SDS-PAGE and Western blotting show
      that the recombinant strain S. lividans [pUWL219-VC] and S. lividans [pLNSP/CTLA
      4] can express CTLA-4 with about MW 13,000 which is similar to those reported
      earlier and have immunoactivity. It is the first time that CTLA-4 expression in
      S. lividans is reported.

PMID- 11838382
TI  - Cloning and high expression of hbFGF with a new strategy.
AB  - Computer program DNASIS v2.5 was used to help designing the site-directed
      mutations for optimizing the expression of hbFGF in E. coli. The secondary
      structure of the translation initiation region (TIR) is a determinant factor for
      translation initiation rate, meanwhile, codon preference plays an important role,
      too. According to the two principles, 4 sites in 5' end of hbFGF cDNA were
      definitely changed, and another 4 sites randomly changed. These mutations will
      lead to potential variation in the secondary structure of TIR. Then computer
      program DNASIS v2.5 was utilized to analyse the total 32 TIR sequences resulted
      from the combination of the 4 randomly mutated sites. Ten sequences with highest
      free formation energy (delta G0) were chosen for subsequent cloning. By PCR using
      synthetic primers containing the 8 changed sites described above, ten hbFGF cDNA
      were amplified and cloned to pET-3c respectively. E. coli strain BL21 (DE3) was
      transformed and induced to express recombinant hbFGF. Two high-expression clones
      were obtained by SDS-PAGE and MTT assay, indicating that computer program-aided
      design for optimizing expression of foreign genes in E. coli is useful.

PMID- 11838383
TI  - [In vitro molecular evolution of humanized mouse ScFv specific against human
      cross-linked fibrin].
AB  - In early work at our laboratory, a mouse ScFv All specific against human cross
      linked fibrin was picked out by using phage displaying technique, and it was
      useful in prepareing targeting thrombolytic agent. To reduce its immunogenicity,
      All was humanized according to the surface reshaping approach. In order to
      increase the affinity and specifity of humanized ScFv, the Mixed HCDR3 and LCDR3
      library was constructed and selected, and five different humanized ScFv with
      better affinity or specifity than humanized ScFv were identified, but the
      affinity of these five humanized scFvs was still lower than parent mouse scFv
      All. In this study, in order to further increase the affinity of humanized scFv,
      the identified five different CDR3 mutant of humanized ScFvs were mutated and
      reassembled with the methods of error-prone PCR and DNA shuffling, then the
      shuffled ScFvs were cloned into plasmid pHB-1 HSCFV to construct ScFv library of
      10(5). The ScFv library was displayed on the surface of phage and panned with
      antigen DD, then five ScFvs with better affinity or specifity were identified by
      using ScFv-alkaline phosphatase detection system which was established in our
      laboratory. Based on identified five better ScFv, the second round error-prone
      PCR and DNA shuffling program was taken out, a ScFv library of 10(6) was
      constructed and selected as before. And four humanized ScFv that had evidently
      better affinity than parent mouse ScFv was identified. This work laid a
      foundation for further research of targeting thrombolitic agent with low
      immunogenicity.

PMID- 11838385
TI  - Using online learning in a traditional face-to-face environment.
AB  - A model for designing online learning was developed and implemented in a
      Registered Nurse-to-Bachelor of Science in Nursing course using online and face
      to-face methodologies. The combination of online and face-to-face learning
      modalities may help the student who is a novice Internet explorer or seasoned Web
      navigator by offering technological support as well as providing constant in
      person feedback regarding course requirements. The face-to-face component
      facilitates a sense of community and peer support that sometimes is lacking in an
      entirely online course. During the 2 semesters this model was used, students
      expressed satisfaction with having the course facilitator/professor physically
      available for consultation and advisement. Evaluation of this online/on-site
      course is ongoing and uses computer-administered qualitative questionnaires, a
      facilitator-moderated focus group, and Likert-type course evaluations.

PMID- 11838384
TI  - The "big bang" implementation: not for the faint of heart.
AB  - Replacing a hospital's obsolete mainframe computer system with a modern
      integrated clinical and administrative information system presents multiple
      challenges. When the new system is activated in one weekend, in "big bang"
      fashion, the challenges are magnified. Careful planning is essential to ensure
      that all hospital staff are fully prepared for this transition, knowing this
      conversion will involve system downtime, procedural changes, and the resulting
      stress that naturally accompanies change. Implementation concerns include staff
      preparation and training, process changes, continuity of patient care, and
      technical and administrative support. This article outlines how the University of
      Missouri Health Care addressed these operational concerns during this dramatic
      information system conversion.

PMID- 11838386
TI  - Diabetes. Can systems change improve outcomes?

PMID- 11838387
TI  - Removal of corneal foreign bodies.

PMID- 11838388
TI  - Why use soap?

PMID- 11838389
TI  - Primary care diabetes. What options are there?
AB  - BACKGROUND: The recognised incidence of type 2 diabetes mellitus is increasing
      dramatically and the vital importance of good diabetes control in patients with
      both type 1 and type 2 diabetes is now well established. Weight reduction and
      oral hypoglycaemic therapy has been accompanied by new drug treatment options in
      type 2 diabetes, while refinements in insulin delivery are more relevant for
      patients with type 1 diabetes. OBJECTIVE: To review currently available drug
      therapies and management strategies for type 2 diabetes, and optimal insulin
      treatment regimens for type 1 diabetes. DISCUSSION: Weight reduction and regular
      exercise remain major lifestyle intervention priorities in type 2 diabetes.
      Metformin should be used early in overweight patients, and sulphonylureas as
      additive therapy. Acarbose, orlistat and the thiazolidinediones all have
      potential roles in the treatment of type 2 diabetes where cardiovascular risk
      factor reduction is also of vital importance. Insulin analogues and continuous
      subcutaneous insulin infusion via insulin pumps will help to optimise insulin
      replacement regimens for patients with type 1 diabetes mellitus.

PMID- 11838390
TI  - Current approaches to diabetes control. How good are they?
AB  - BACKGROUND: How well are general practitioners currently managing their patients
      with diabetes and do systems of care have anything to offer? OBJECTIVE: This
      article examines the benefits and costs of recommended treatments. It looks at
      evidence on current standards of care for people with diabetes in Australia. It
      examines the evidence on systems of care and their effect on quality of care and
      outcomes. DISCUSSION: There is good evidence to support current recommendations
      regarding management of glycaemia, blood pressure, hyperlipidaemia and the use of
      aspirin. Early screening and appropriate management of retinopathy,
      microalbuminuria and at-risk feet is also supported. Despite this, management of
      diabetes within the Australian community remains suboptimal. Systems of care
      improve quality of care. The uptake of these more structured approaches to care
      requires an appropriate mix of incentives, education and support for GPs.

PMID- 11838391
TI  - Enhanced primary care items. Their use in diabetes management.
AB  - BACKGROUND: The Enhanced Primary Care (EPC) items for care planning and case
      conferencing provide an opportunity for better quality care for people with
      chronic disease. OBJECTIVE: To explore the use of the EPC items in the structured
      care of diabetes based on evidenced based guidelines in general practice.
      DISCUSSION: Care planning and case conferencing are useful, especially in the
      structured care of patients who have poor control. The achievement of better
      health outcome for these patients depends upon a patient oriented and structured
      approach in collaboration with other health professionals. This needs to be
      supported by systems within the practice, Division and local community.

PMID- 11838392
TI  - Diabetes screening. Does it make a difference in the Aboriginal and Torres Strait
      Islander population?
AB  - BACKGROUND: The prevalence of diabetes in the Aboriginal and Torres Strait
      Islander population is relatively high. A high proportion of cases are
      undiagnosed. Diabetes is one of a number of increasingly prevalent chronic
      diseases which have been described collectively as a noncommunicable disease
      epidemic. OBJECTIVE: To review the existing literature relating to the actual or
      potential benefit of screening for diabetes in the Aboriginal and Torres Strait
      Islander population. DISCUSSION: There is a strong case for screening for
      diabetes as part of an opportunistic or planned periodic health examination
      (PHE). As well as fasting venous plasma glucose, this integrated approach should
      include assessment of weight, blood pressure, presence of microalbuminuria and
      hyperlipidaemia. General practitioners need to be sensitive to cultural issues
      and power relationships, as well as considering 'structural' impediments to good
      health, such as affordability and availability of nutritious food, rather than
      focus solely on individual 'lifestyle' issues.

PMID- 11838393
TI  - New antidiabetic medications. Clinical evidence, clinical practice and
      pharmacoeconomics.
AB  - BACKGROUND: Type 2 diabetes is a progressive and complex disease with underlying
      defects in insulin sensitivity, insulin secretion and hepatic glucose production.
      There is a range of antidiabetic treatment options now available to address these
      defects. Determination of which therapy for which patient is not always apparent
      from the clinical literature or the product information. OBJECTIVE: To summarise
      the extent and use of clinical evidence, clinical practice and pharmacoeconomics
      in positioning antidiabetic agents in Australian clinical practice. DISCUSSION:
      This paper summarises the introduction of new agents into the options for
      treatment of type 2 diabetes through the Pharmaceutical Benefits Scheme.
      Combining evidence based medicine, accepted clinical practice and decision
      analysis, allows the controlled introduction of new therapies in a climate of
      limited resources and a population with increasing therapeutic needs.

PMID- 11838394
TI  - Pneumococcus. Threatening the under-twos.

PMID- 11838395
TI  - Regional nerve blocks. Part 8--Using a nerve stimulator to locate peripheral
      nerves.
AB  - This is a relatively specialised technique aimed more at enhancing the skills of
      doctors regularly performing local anaesthetic blocks. It is a useful device for
      confirming the location of major nerves and plexuses proximally, but not
      necessary for most peripheral nerve blocks.

PMID- 11838396
TI  - Practice tip. Exercise for the lower back.

PMID- 11838397
TI  - Herbal medicine. What is the evidence?
AB  - This is the final in the series of 13 articles looking at current herbal therapy.
      It reviews those plants with clinical and scientific evaluation sufficient to
      consider adoption into orthodox medicine. Surprisingly some commonly used herbs,
      such as the purple coneflower (Echinacea purpura), valerian and ginseng, do not
      as yet pass the test, but others such as St John's wort, ginkgo, saw palmetto now
      have sufficient clinical studies to consider orthodox use. With the huge interest
      in herbal treatment it is likely that other plants will join the list following
      adequate clinical evaluation.

PMID- 11838398
TI  - Helping families of patients with a mental illness.
AB  - BACKGROUND: Families with a mentally ill member face a number of difficulties and
      issues. OBJECTIVE: This paper follows on from an earlier paper which examined the
      impact of mental illness on family members. Here the author explores some of the
      ethical and procedural difficulties in dealing with families and offers simple
      suggestions to general practitioners to help patients and families. DISCUSSION:
      Family members often approach GPs for help when a relative develops a mental
      illness. Generally family members will seek information and help, not only to
      deal with their own distress, but to help in dealing with the patient's actions
      and distress, and intervention with others treating the family member.

PMID- 11838399
TI  - Cross cultural tensions. It is challenging to communicate.
AB  - A cross cultural environment emphasises the challenges for communication between
      doctor and patient. The following stories share our thoughts and experience. They
      aim to illustrate issues and provoke reflection.

PMID- 11838400
TI  - Birth, death and life.

PMID- 11838401
TI  - Medical fees. A history of how the doctor was paid in Australia.
AB  - Medical fees are an important part of medical practice, yet they have always been
      a bone of contention. This article is the first in a series of three that will
      look at the way the doctor was paid. It examines the role of medical fees in
      early medical practice in Australia.

PMID- 11838402
TI  - Paediatric vaccination practice in a division of general practice.
AB  - BACKGROUND: Currently the National Health and Medical Research Council (NH&MRC)
      recommend the use of a 23 gauge, 25 mm long needle inserted 45-60 degrees into
      the anterolateral thigh for paediatric vaccination. AIM: To assess the compliance
      of general practitioners (GPs) in a rural practice division with vaccination
      practice (site and needle size and gauge) prescribed for infants and toddlers by
      the NH&MRC. METHOD: In 1999, a questionnaire survey was sent by the divisional
      office to all 150 GPs in the Hunter Rural Division of General Practice. The
      questionnaire collected demographic data (age, gender, university of graduation,
      number of paediatric vaccines administered per week) and elicited responses about
      the site of vaccination and the size and gauge of needle to be used for children
      2-18 months and 18 months and older. RESULTS: Completed questionnaires were
      available from 112 GPs (74.6% completion rate). There was a high level of
      compliance with the NH&MRC proscription of buttock vaccination with only 4.3% and
      4.1% of responses to the question of vaccination site at 2-18 months and 18
      months and older respectively nominating this site. The anterolateral thigh was
      the favoured site for vaccination in children 2-18 months old (77.5% of
      responses) with the deltoid being the favoured site in children 18 months and
      older (59.2% of responses). There was a very low level of compliance with the
      NH&MRC recommended standard needle (23 gauge, 25 mm long, blue hub needle) (3.5%
      of responses). The orange hub needle (25 gauge, 16 mm long needle) was most
      favoured (48.7% of responses) with additional strong support for the 25 gauge, 25
      mm long needle (40.2% of responses). CONCLUSION: In the Hunter Rural Division of
      General Practice there was good compliance with the NH&MRC's recommendations for
      site of vaccination, but not needle size and gauge to be used in infants and
      small children. Imprecise wording of these recommendations has created apparent
      uncertainty about the site of vaccination of children at 18 months of age.

PMID- 11838404
TI  - The use of single case studies by academic general practitioners.
AB  - OBJECTIVE: To compare the use of the single case for teaching, clinical, and
      research by academic general practitioners (GPs) with other academic specialists.
      METHOD: A questionnaire study involving all four departments of general practice
      in New Zealand and other academic departments from the Wellington School of
      Medicine. The main outcome measures were respondents' publication history,
      details of the last single case they published, the use of single cases for
      teaching, and opinion of the usefulness of the single case in teaching, clinical,
      and research work. RESULTS:  SUBJECT: 33 academic GPs and 41 other academic
      specialists (response rate was 97% versus 79%). All doctors reported 3.6% of all
      their publications were as single cases. General practitioners were less likely
      to publish at least one single case compared to specialist (24% versus 59%). The
      characteristics of the single cases published varied widely with 70% categorised
      as 'rare' or 'first ever' cases of a disease or problem. More GPs compared to
      specialists thought cases encountered in clinical work could influence subsequent
      cases (100% versus 83%). All doctors considered single cases to be useful for
      teaching and clinical uses, but only a little useful for research. However, 23%
      of all doctors stated that a single case had been a stimulus for their own
      research work. Furthermore, a textual analysis found doctors used single cases as
      examples of research possibilities and to influence other doctors. DISCUSSION:
      Single cases had important teaching and clinical uses among academic doctors.
      However, GPs were less likely to publish single cases than their specialist
      colleagues. This may reflect the smaller pool of academic GPs in New Zealand.
      Single cases were ranked low among research methodologies, but were considered to
      have an important triggering role for doctors doing research.

PMID- 11838403
TI  - An instrument for collecting problem oriented, problem linked data in primary
      medical care.
AB  - AIM: To describe a new form for collecting problem oriented, problem linked data
      from primary care. METHOD: A novel form is described which has been used to
      collect these data. These data were validated against secondary data collections.
      RESULTS: The form has been used to record 10,937 encounters in a variety of
      primary care settings. The form was acceptable to general practitioners (GPs) and
      was completed on 87% of eligible patients in a one week data collection. Data
      captured provide descriptive data about the problems encountered and services
      provided during the consultation. These elements of the medical record are linked
      so that it is possible to address questions about patterns of service provision.
      Uncomplicated lower urinary tract infection is used as an example of how data
      from the form can be used to examine clinical practice and resource utilisation.
      CONCLUSION: A method has been demonstrated to collect problem oriented, problem
      linked data which may be used for clinical costing and to demonstrate compliance
      with clinical practice guidelines.

PMID- 11838405
TI  - Past-present-and-future@20 years .

PMID- 11838406
TI  - Organ transplantation.
AB  - As people live longer due to using potent anti-HIV therapy, there appears to be
      an increase in the percentage dying from non-AIDS defining conditions, including
      organ failure. Long-term infection with hepatitis B or C can lead to liver
      failure. Some research suggests that liver disease is accelerated when a person
      is also fighting HIV. Transplantation is virtually the only option for people
      with severe liver disease. HIV-related kidney diseases, specifically HIV
      associated nephropathy, is of major concern to African Americans and represents
      the third leading cause of end-stage kidney failure in African American adults.
      Other causes of organ failure may include side effects of therapies to treat HIV
      and associated conditions. In cases of organ failure, transplantation is the only
      viable option. For people with kidney dysfunction, dialysis may provide a short-
      or even long-term solution. For people with HIV experiencing organ failure,
      transplantation needs to be an option.

PMID- 11838407
TI  - New discoveries in HIV research.
AB  - Over the past twenty-years there has been a vast wealth of discoveries in HIV
      research, perhaps unparalleled in the history of biomedical investigation. Since
      the early days of the epidemic, scientists' understanding of HIV and the immune
      system has advanced by leaps and bounds. Yet, the fruits of very basic science
      research do not always show themselves immediately. Certainly the scientific
      process is far from ideal in translating information learned in the laboratory to
      therapy and patient care advances at the bedside. Still, advances in basic
      science have greatly improved the care of people living with HIV. This article
      will briefly overview a few major discoveries and shed light on a new emerging
      theory about the role and implications of cholesterol in HIV infection.

PMID- 11838408
TI  - Time to get involved, again.
AB  - The federal government's response to the HIV/AIDS epidemic in the United States
      has improved greatly over the past 20 years although there are still many
      challenges. In the earliest years, it was often hard enough simply to have key
      policymakers utter the word "AIDS" and acknowledge that there was a problem.
      Driven by the devastation of a deadly epidemic and confronted with a lack of
      treatment options, people living with HIV/AIDS and their advocates took up the
      fight for a reasonable government response. At the same time, we were forced to
      develop an unprecedented community care structure. Federal advocacy focused with
      urgency on researcher and regulatory reforms and securing funding for research,
      care, treatment, prevention, and housing programs. At the same time, we had to
      fight many attempts at passing harmful or discriminatory legislation and to
      guarantee protection from institutional and private bias.

PMID- 11838409
TI  - Drug level monitoring: the next advance in diagnostics.
AB  - The past few years have brought major advances in the treatment and management of
      people with HIV. In many of the early trials for HIV-positive people, different
      blood markers were studied to determine whether they might be beneficial in
      monitoring the health of people with HIV and whether they might be able to
      predict the risk of disease progression. Many were deemed not useful including
      beta-2 microglobulin, neopterin and p24 antigen. Others have become part of
      routine standard of care including CD4+ cell counts, viral load (HIV RNA levels)
      monitoring and resistance testing. Many other blood markers are still being
      evaluated although the next major advance is likely to come from the field of
      pharmacology and specifically, therapeutic drug monitoring (TDM). Pharmacology is
      the study of how drugs are absorbed, broken down (metabolized) and eliminated in
      the body. TDM monitors the level of various drugs in the bloodstream.

PMID- 11838410
TI  - Women and AIDS at twenty.
AB  - AIDS, first reported in women in 1981, has decidedly become a major concern for
      women and girls. Early misconceptions about women's perceived lack of HIV risk
      and the characterization of AIDS as a disease primarily affecting gay men
      thwarted attention afforded to women's issues early in the epidemic. Today, women
      account for 32% of new HIV diagnoses in the United States. Globally, women make
      up more than half of those infected with HIV/AIDS. As women shoulder an
      increasing burden of HIV, research, medical and activist responses to women's
      issues increase. And while more is known about and being done about women and HIV
      today, basic questions and gaps remain.

PMID- 11838411
TI  - [Palliative medicine].

PMID- 11838412
TI  - [Terminally ill cancer patients at home. Experiences with a hospice-based
      palliative care].

PMID- 11838413
TI  - [The effect of specialized palliative intervention].

PMID- 11838414
TI  - [Palliative intervention in primary health care].

PMID- 11838415
TI  - [Palliative sedation].

PMID- 11838416
TI  - [Palliative chemotherapy in patients with metastatic colorectal cancer].

PMID- 11838417
TI  - [The myelodysplastic syndrome I. Pathogenesis, clinical symptoms, diagnosis and
      differential diagnosis].
AB  - The myelodysplastic (MDS) syndrome is characterized by variable cytopenia, owing
      to bone marrow insufficiency. Known provoking factors for the disease are
      chemicals (benzene), previous treatment with alkylating agents, and radioactive
      irradiation. The pathogenesis involves an acquired lesion of the pluripotent
      haematopoietic stem cell with the evolution of a (pre-)malignant cell clone with
      an increased proliferation potential, but, in addition, severe dysplasia with
      ineffective haematopoiesis. An increased intramedullary production of various
      cytokines that inhibit haematopoiesis, including tumour necrosis factor alpha
      (TNF-alpha), may be responsible for the accelerated cell death (apoptosis). An
      increasing genetic instability during the course of the disease causes
      progression of the cytopenia with anaemia, infections, and bleeding. Autoimmune
      diseases may be seen. The disease often progresses to acute myeloid leukaemia. A
      chromosomal analysis is important, as 40-50% of the patients have chromosomal
      changes at the time of diagnosis. Differential diagnostic considerations include
      temporary dysplasia provoked by medical or toxic agents, B12 or folate
      deficiency, infectious bone marrow involvement (HIV, CMV infection), chronic
      alcoholism, aplastic anaemia, and myelofibrosis.

PMID- 11838418
TI  - [The myelodysplastic syndrome II. New therapeutic principles, course and
      prognosis].
AB  - The treatment of the myelodysplastic syndrome (MDS) has formerly been supportive,
      primarily blood transfusions. Treatment with the growth factor erythropoietin, in
      combination with granulocyte-colony stimulating factor or granulocyte-macrophage
      colony stimulating factor is accompanied by a decline in the need for blood
      transfusions in about 40% of the patients. Likewise, the risk of infections is
      reduced. Immunosuppressive therapy with cyclosporine and antithymocyte globulin
      is also capable of improving the cytopenia in about 50% of the patients.
      Allogeneic bone marrow transplantation is the only possibility of cure in MDS,
      but the procedure is associated with high mortality. This treatment modality is
      therefore only recommended for younger patients, who are in a complete remission
      after being treated for acute myeloid leukaemia or are otherwise in a high risk
      group. The prognosis is poor, with an overall median survival of about 15 months.
      A simple scoring system has been elaborated and is based upon the percentage of
      myeloblasts in the bone marrow, a chromosomal analysis, and the number of cell
      lines with cytopenia. This system is able to distinguish between three distinct
      groups of patients with a highly different prognosis (low, intermediate, high
      risk), which is also of importance when evaluating the best treatment for the
      individual patient.

PMID- 11838419
TI  - [Lung cancer: survival rate differences in Danish counties. Survival analysis of
      33.838 patients during the period 1984-1998].
AB  - INTRODUCTION: The quality of care for Nordic cancer patients has been considered
      to be low in Denmark. Our quality problem was believed to be caused by the
      structure of our secondary health care. But there may be other explanations for
      the poor survival in Denmark, and the comparison with the other Nordic countries
      may be flawed by confounding factors, such as smoking habits and spread of cancer
      at the time of diagnosis. We therefore, analysed differences in regional survival
      after diagnosis of carcinoma of the lung in Denmark to look for signs of similar
      flaws. MATERIALS AND METHODS: A sample from the National Cancer Registry of all
      cases of carcinoma of the lung, diagnosed in 1984-1995. Persons older than 80
      were excluded. Age and spread of cancer were included in a Cox analysis. RESULTS:
      Survival was dependent on residence. Within the first five months of diagnosis,
      survival was significantly poorer in Copenhagen City and better in the counties
      of Aarhus, Aalborg, and Viborg. At five months, the differences had diminished
      and only the counties of Fyn and Sonderjylland differed from the nationel average
      in a negative way. DISCUSSION: Better results were achieved than previously
      expected in some Danish counties. Interpretation of the Nordic results should be
      more critical and include possible confounders, such as smoking and spread of
      cancer at diagnosis. The Danish problem with cancer may be because of the delay
      of patient and doctor in the primary health care, together with an extreme life
      style, including too much urban life and tobacco smoking.

PMID- 11838421
TI  - [Research activities at a department of palliative medicine].

PMID- 11838420
TI  - [Trimethoprim-sulfamethoxazole as antibacterial prophylaxis during induction
      therapy of children with acute lymphatic leukemia].
AB  - INTRODUCTION: Children with acute lymphoblastic leukaemia (ALL) are treated with
      intensive chemotherapy, which results in profound immunosuppression. Treatment
      with trimethoprim/sulphamethoxazole (TMP-SMX) is therefore used in some
      departments as prophylaxis against infections with both bacteria and Pneumocystis
      carinii. The use of TMP/SMX for prophylaxis during the induction therapy is not
      uniform in the four departments of paediatric oncology in Denmark. This gave us
      the opportunity to describe the effect of TMP/SMX on bacterial infections in
      children with ALL during the induction therapy. MATERIAL AND METHODS: Between 1
      January 1992 and 31 December 1997, 210 children were diagnosed with ALL in
      Denmark. From a retrospective review of the medical charts, the number of
      children with fever (> 38 degrees C), the number of febrile days, days of
      antibiotic treatment, and the number of positive blood cultures were registered
      for each febrile episode. RESULTS: One hundred and fourteen children received
      TMP/SMX prophylaxis (10-30 mg/SMX/kg/day) and 76 did not. Children who received
      TMP/SMX prophylaxis had significantly fewer episodes of fever (66/114 (58%) vs.
      60/76 (79%), p < 0.01) and significantly fewer children who received the
      prophylaxis had positive blood cultures before the start of antibiotic treatment
      compared with children who did not receive prophylaxis (23/114 (20%) vs 37/76
      (49%), p < 0.001)). Nineteen different species were isolated from the blood
      stream before the start of antibiotic treatment. In the non-prophylaxis group
      there were a preponderance of isolates with Staph. aureus, Str. pneumoniae, E.
      coli, and P. aeruginosa. There was no difference in the mortality between the two
      groups (p = 0.44). There were no cases of P. carinii pneumonia in the period of
      induction therapy. DISCUSSION: TMP/SMX prophylaxis during induction therapy for
      childhood ALL seems to reduce the risk of bacteraemias and febrile illness.

PMID- 11838422
TI  - [Local antibiotic prophylaxis reduces the incidence of nosocomial pneumonia among
      critically ill patients].

PMID- 11838423
TI  - [Interview with Dame Cicely Saunders].

PMID- 11838424
TI  - [Palliative medicine education].

PMID- 11838425
TI  - Oxidation of [Fe(CN)6]4- and reduction of [Fe(CN)6]3- in VUV-irradiated aqueous
      solutions.
AB  - Vacuum ultraviolet (VUV) photolysis is one of the straightforward alternatives
      method among the advanced oxidation processes (AOPs) for the elimination of
      pollutants from water and air. The VUV photolysis of water produces hydroxyl
      radicals and hydrogen atoms, which have widely different oxidation and reduction
      abilities. In this work the oxidation and reduction properties of VUV-irradiated
      solutions were compared by investigating the reduction of [Fe(CN)6]3- and the
      oxidation of [Fe(CN)6]4-. The rate of oxidation of [Fe(CN)6]3- was found to be
      practically the same as the reduction rate of [Fe(CN)6]4- in the irradiated
      oxygen-free solutions under identical conditions. Dissolved oxygen strongly
      influences the redox properties of this system.

PMID- 11838426
TI  - Influence of dissolved humic substances on the leaching of MCPA in a soil column
      experiment.
AB  - The influence of dissolved humic substances on the transport of (4-chloro-2
      methylphenoxy) acetic acid (MCPA) in a sandy soil with a low organic carbon
      content was studied in a column experiment. Soil columns were eluted with aqueous
      solutions containing different fractions of humic substances. More than 70% of
      the applied compound was found in the leachate in all sandy soil experiments, but
      distinct differences were obtained depending on the composition of the eluent.
      The addition of both humic and fulvic acids to the eluent affected the leaching
      behaviour of MCPA. While the presence of humic acids increased and accelerated
      the movement of MCPA in the investigated sandy soil, fulvic acids caused the
      opposite effect: increased retention was observed relative to the control. We
      concluded that a possible carrier transport or retention strongly depends on the
      composition of the dissolved organic matter. Thus, changes in the composition of
      dissolved organic matter may affect MCPA movement into deeper soil layers.

PMID- 11838427
TI  - Metal pollution in Spanish terrestrial ecosystems during the twentieth century.
AB  - We show here additional biological evidence of the alteration in global
      biogeochemistry by human activities during the twentieth century. The mineral
      concentration of herbarium specimens of 24 species of vascular plants and three
      species of bryophytes collected in North and East regions of Spain have
      substantially changed throughout the twentieth century. While V, a proxy tracer
      of oil pollution, exponentially increased in the last decades, other metals such
      as Cr, Ba, Sr, Al, Fe, Pb, Cd and Ti increased up to 1960-1970 and started to
      decrease in 1985-1995, when environmental legal regulations started to be
      effective. Multivariate principal component analysis showed an overall change in
      plant elemental concentrations throughout the different decades of the century
      and a clear separation of vascular plants and bryophytes. Likely important
      consequences for ecosystem structure and functioning and even for human health
      may be expected from these changes in mineral concentration.

PMID- 11838428
TI  - Dechlorination of polychlorinated dibenzo-p-dioxins catalyzed by noble metal
      catalysts under mild conditions.
AB  - Dechlorination of polychlorinated dibenzo-p-dioxins such as 2,7-dichlorodibenzo-p
      dioxin (2,7-DCDD) and 1,2,6,7-tetrachlorodibenzo-p-dioxin (1,2,6,7-TCDD) was
      carried out in a solution of NaOH in 2-propanol in the presence of carbon
      supported noble metal catalyst (Pd/C or Rh-Pt/C) at temperatures between 23 and
      35 degrees C. At initial concentrations of 140-240 micrograms/ml, 2,7-DCDD and
      1,2,6,7-TCDD were efficiently converted to a chlorine-free product, dibenzo-p
      dioxin (DD), in high yield (60-80%). The conversion of 2,7-DCDD and 1,2,6,7-TCDD
      and the yield of DD were hardly affected by the atmosphere (N2 or air). We
      postulate that the displacement of aromatic chlorines by hydrogen selectively
      occurs on the catalyst, involving hydrogen-transfer from 2-propanol to the
      substrates.

PMID- 11838429
TI  - Structure elucidation of four possible biogenic organohalogens using isotope
      exchange mass spectrometry.
AB  - The molecular structures of four unknown bioaccumulating halogenated compounds,
      C10H6N2Br3Cl3, C10H6N2Br4Cl2, C10H6N2Br5Cl, and C10H6N2Br6 were characterized
      using isotope exchange positive chemical ionization (IE-PCI) mass spectrometry
      (MS) and identified by comparison to synthesized standards. NH3 and ND3 were used
      as reagent gases for the IE-PCI-MS experiment. The shift in mass of the
      quasimolecular ion between the NH3 and ND3 PCI obtained spectra indicated the
      number of exchangeable hydrogens attached to the two nitrogen atoms in
      C10H6N2Br4Cl2, and thus the type of amines present (primary, secondary, or
      tertiary). 19 compounds (13 amines of varying degree of substitution; six
      containing no nitrogen) were used as reference compounds and controls in the
      experiment to validate the IE-PCI technique. The results of the IE-PCI-MS
      indicated the presence of two tertiary amine functional groups. The molecular
      structures of the four hexahalogenated compounds were then proposed to be 1,1'
      dimethyl-3,3',4,-tribromo-4',5,5'-trichloro-2,2'-bipyrrole, 1,1'-dimethyl
      3,3',4,4'-tetrabromo-5,5'-dichloro-2,2'-bipyrrole, 1,1'-dimethyl-3,3',4,4',5
      pentabromo-5'-chloro-2,2'-bipyrrole, and 1,1'-dimethyl-3,3',4,4',5,5'-hexabromo
      2,2'-bipyrrole and subsequently synthesized. Comparison of retention times and
      electron capture negative ionization (ECNI) full scans on various gas
      chromatography (GC) columns between the synthesized bipyrroles and the
      corresponding unknown compounds in biota indicated that three of the unknown
      compounds--possible marine natural products--were the proposed halogenated
      dimethyl bipyrroles. The placement of the halogen atoms on the fourth compound,
      C10H6N2Br3Cl3 could not be unequivocally determined since the synthesized
      standard could not be fully characterized.

PMID- 11838430
TI  - Biotransformation of phenylurea herbicides by a soil bacterial strain,
      Arthrobacter sp. N2: structure, ecotoxicity and fate of diuron metabolite with
      soil fungi.
AB  - In order to assess the influence of the aromatic substitution on the ability of a
      soil bacterial strain, Arthrobacter sp. N2, to degrade phenylurea herbicides,
      biotransformation assays were performed in mineral medium with resting cells of
      this soil bacterial strain on three phenylurea herbicides (diuron, chlorotoluron
      and isoproturon). Each herbicide considered, led to the formation of only one
      metabolite detected by HPLC analysis. After isolation, the metabolites were
      identified by NMR and MS, as the corresponding substituted anilines. According to
      the Microtox test (realized on the bacterium Vibrio fischeri), these metabolites
      presented non-target toxicity far more important (up to 600 times higher for 4
      isopropylaniline) than the parent molecule. For isoproturon and chlorotoluron,
      the amount of substituted anilines obtained at the end of the biotransformation
      was very low, whereas the biotransformation of diuron into 3,4-dichloroaniline
      was almost quantitative. In this last case, the degradation product accumulated
      in the medium. In soil, other microorganisms are present that might degrade it.
      So the biotransformation of 3,4-dichloroaniline was then tested with four fungal
      strains: Aspergillus niger, Beauveria bassiana, Cunninghamella echinulata var.
      elegans and Mortierella isabellina. The aniline was further transformed with all
      the microorganisms tested. Only one metabolite was detected by HPLC analysis and
      after isolation, it was identified to be 3,4-dichloroacetanilide. This acetylated
      compound led to biological effects less important on V. fischeri than 3,4
      dichloroaniline. These results stress the importance of identifying the
      degradation products to assess the impact of a polluting agent. Indeed, the
      pollutant may undergo transformation yielding compounds more toxic than the
      parent molecule.

PMID- 11838431
TI  - Isolation, characterization and diuron transformation capacities of a bacterial
      strain Arthrobacter sp. N2.
AB  - A bacterial strain able to transform diuron was isolated from a soil by
      enrichment procedures. Strain isolation was realized by plating on minimal
      agarose medium spread with this herbicide and selecting the colonies surrounded
      by a clear thin halo. One strain was characterized and identified as an
      Arthrobacter sp. It metabolized diuron and the final transformation product, 3,4
      dichloroaniline, was produced in stoichiometric amounts. The transformation of
      diuron at different concentrations was more efficient in the presence of
      alternative sources of carbon and nitrogen. The bacterial activity was also
      evaluated in soil microcosms with a consequent disappearance of diuron and
      concomitant appearance of 3,4-dichloroaniline, of which the concentration
      decreased thereafter. Bacterial cells inoculated in the microcosms survived as
      viable but eventually nonculturable cells.

PMID- 11838432
TI  - Biomonitoring metal deposition in Galicia (NW Spain) with mosses: factors
      affecting bioconcentration.
AB  - Three factors (canopy effect, lithology and seasonal variations) that may
      influence the concentrations of metals in terrestrial mosses were studied. The
      levels of 17 elements were determined in terrestrial mosses (Scleropodium purum
      (Hedw.) Limpr, and Hypnum cupressiforme Hedw.) collected from 75 sites in Galicia
      at two sampling times, in 1995 and 1997. In addition, monthly samples of S. purum
      were collected throughout a period of one year from four sites in the same area,
      for analysis of levels of eight elements. The first studied factor, collection of
      mosses from areas under tree cover, did not influence significantly the levels of
      the elements analysed. The second factor studied was the dominant lithology in
      the sampling area (granite, slate and schist). No significant differences were
      found between samples from sites where granites and slates dominated. Significant
      differences were found in the levels of Co, Cr, Ni and Mn in both species growing
      in granite and slate substrate areas when compared with those growing in schist
      areas. This was also found for Al and Fe in S. purum and for As in H.
      cupressiforme. The third factor investigated, using the results from the monthly
      survey, was the seasonal effect. No significant differences were found in the
      concentrations of all elements in S. purum throughout the year.

PMID- 11838434
TI  - Surfactant-assisted UV-photolysis of nitroarenes.
AB  - Photochemical transformations (lambda-254 nm) of 2,4-dinitrotoluene (2,4-DNT) in
      aqueous solutions containing the cationic surfactant cetyltrimethylammonium (CTA)
      and the anionic nucleophile borohydride (BH4-) were investigated. The overall
      decay rate was enhanced at CTA concentrations above the critical micelle
      concentration (cmc) when stoichiometric excess BH4- was present in solution. A
      kinetic model that separates the overall reaction rate into micellar and aqueous
      pseudo-phase components indicates transformation in micelles is 17 times faster
      that in the homogeneous water phase under those conditions investigated.
      Intermediate products were identified by comparing the HPLC retention times and
      ultraviolet-visible absorption spectra of product peaks to those of analytical
      standards. 2-Methyl-5-nitroaniline, 4-nitrotoluene, 2-nitrotoluene, 4-methyl-3
      nitroaniline, 2,4-diaminotoluene, o-toluidine, 1,3-dinitrobenzene, 3
      nitroaniline, p-cresol, and 2,4-diaminophenol were identified as photo
      transformation intermediates or products.

PMID- 11838433
TI  - Partitioning and bioaccumulation of cadmium in artificial sediment systems:
      application of a stable isotope tracer technique.
AB  - The utility of stable isotope tracers for investigating the relationship between
      cadmium (Cd) partitioning in artificial sediment-water systems and Cd
      accumulation in a benthic detritivore (Asellus racovitzai, Isopoda) was explored.
      In the laboratory, Cd isotopes were applied to synthetic sediment and isotope
      concentrations were measured in sediment, overlying water and exposed asellids
      over a 10-day period. Isotope ratios measured in sediment and water were compared
      to ratios measured in asellids to determine whether Cd partitioning could predict
      metal bioaccumulation. Two different parameters which might affect Cd
      partitioning between the sediment and overlying water compartments were
      investigated: the chemical form in which Cd was added to systems, and the organic
      matter content of the sediment. To test the effect of chemical form on Cd
      partitioning, three isotopes of cadmium were individually applied to formulated
      sediment in varying combinations of 113Cd(NO3)2, 112Cd-humic acid (HA) 114CdSO4.
      The results demonstrated that chemical form did not influence partitioning, as
      the Cd isotope that was applied to sediment in the nitrate form exhibited similar
      partitioning between sediment and overlying water as the isotope that was applied
      in the sulfate or HA form. However, Cd isotope concentrations in overlying water
      were strongly related to the pattern of isotope accumulation in asellids
      suggesting that overlying water concentrations determined Cd bioaccumulation. In
      contrast, when the organic matter content of sediment was increased through the
      addition of Sphagnum peat moss, total Cd concentrations in overlying water and
      tissue were low, and there was no relationship between Cd-isotope concentrations
      in tissue and water. These results indicate that Cd accumulation occurred
      primarily from water, and factors that increase metal partitioning to sediment,
      such as increased sediment organic matter content, decrease Cd accumulation in
      asellids. The stable isotope tracer method described herein appears to be a
      useful technique for investigating the relationship between metal partitioning
      and bioaccumulation in simple sediment systems, but could also be extended to
      more complex systems, and used with different metals that have multiple stable
      isotopes.

PMID- 11838435
TI  - Photoassisted bleaching of dyes utilizing TiO2 and visible light.
AB  - Titanium dioxide was shown to be generally effective as a catalyst for
      photobleaching many structural classes of organic dyes in aqueous solution, using
      visible light. However, results from study of 15 dyes indicate that
      photobleaching rates differ significantly from families of dyes with different
      functionalities, and are dependent on the light source and crystalline form of
      TiO2 used. Sorption characteristic on the TiO2 surface and the aqueous solubility
      of the dyes also play an important role in the photobleaching rate. Kinetic
      analysis indicates that the dye photobleaching rates can usually be approximated
      as pseudo-first-order kinetics. In addition to the generally proposed
      photocatalytic oxidation mechanism for TiO2 reactions, we observed evidence for
      two kinds of electron transfer mechanisms that are "photosensitized reduction"
      and "photosensitized oxidation". Natural sunlight was effectively used to
      photobleach some of the dyes.

PMID- 11838436
TI  - Oxidation of organophosphorus pesticides for the sensitive detection by a
      cholinesterase-based biosensor.
AB  - A potentiometric flow injection-type biosensor developed in our laboratory was
      used for the determination of organophosphorus pesticides (OPs). The principle of
      the biosensor is that the degree of inhibition of a sensor enzyme by an OP is
      dependent on the concentration of the pesticide. The sensor system consisted of a
      reactor with acetylcholinesterase (AChE) immobilized on a controlled pore glass
      and a detector with a tubular H(+)-selective membrane electrode. In order to
      examine the possibility of enhancing the sensitivity of the sensor by converting
      OPs to oxidized forms (stronger inhibitors), a comparison of the degree of enzyme
      inhibition by OPs at 10(-6) M before and after their oxidation was made. All of
      the ten pesticides tested exhibited greater inhibitory power toward the sensor
      enzyme following oxidation. All of the oxidized pesticides at 10(-6) M inhibited
      the sensor enzyme to a considerable degree, demonstrating the utility of the
      developed method for the class-specific determination of OPs. A calibration curve
      for diazinon, over the concentration range of 10(-11)-10(-4) M, was obtained. The
      lower detection limit was 2 x 10(-10) M. Treatment of the inhibited enzyme with
      pyridine-2-aldoxime restored the enzyme to near full activity, allowing repeated
      use of the sensor.

PMID- 11838437
TI  - [Physiopathology of head and neck neoplasms in the aged].

PMID- 11838438
TI  - Reassessing the mathematical modeling of the contribution of vasomotion to
      vascular resistance.

PMID- 11838439
TI  - Phosphorylation of HSP20 on serine 157.

PMID- 11838440
TI  - Screening for Turner's syndrome by chromosome analysis of all girls with short
      stature.

PMID- 11838441
TI  - Developing effective and affordable models for non-communicable disease
      prevention and control.

PMID- 11838442
TI  - Thoracic outlet syndrome caused by chronic retrosternal dislocation of the
      clavicle. Successful treatment by transaxillary resection of the first rib.
AB  - Traumatic posterior dislocation of the sternoclavicular joint is an unusual
      injury. We report a rare, late complication in the form of a thoracic outlet
      syndrome. Resection of the first rib resulted in prompt and complete resolution
      of the symptoms and would appear to be the appropriate treatment, avoiding the
      complications associated with resection of the clavicle.

PMID- 11838443
TI  - Treatment of unstable fractures of the forearm in children.

PMID- 11838444
TI  - Interobserver variations in intra-articular evaluation during arthroscopy of the
      knee.
AB  - We carried out a prospective study in order to establish to what extent the intra
      articular evaluation undertaken during arthroscopy of the knee differed between
      surgeons. Two senior specialist registrars and a consultant orthopaedic surgeon
      with a special interest in knee surgery were involved. A total of 78 knee
      arthroscopies (78 patients) was studied. Arthroscopy was first carried out by the
      trainee and then by the senior author (ACWH). The intra-articular evaluation
      during the arthroscopy was recorded independently by a third person in the
      operating theatre. Data were collected to record variations in examination under
      anaesthesia, the morphology and pathology of the menisci and anterior cruciate
      ligament and the state of the articular surfaces. The overall interobserver
      variation was 20% in all categories. We question the published results of intra
      articular evaluation during knee arthroscopy when surgeons of different levels of
      experience are involved in a single study.

PMID- 11838445
TI  - The Souter-Strathclyde elbow arthroplasty. A clinical and radiological study of
      525 consecutive cases.
AB  - We present the results of 525 primary Souter elbow arthroplasties undertaken in
      406 patients between 1982 and 1997. There were 372 women and 34 men with a mean
      age of 57 years; 119 patients had a bilateral procedure. The elbows were affected
      by chronic inflammatory disease, usually rheumatoid arthritis, which had been
      present for a mean of 24.7 years (2 to 70). In about 30% the joints were grossly
      destroyed with significant loss of bone. In 179 elbows the ulnar components were
      metal-backed and retentive; in the remaining 346, with better bone stock, non
      retentive, all-polyethylene prostheses were used. Because of complications, 108
      further operations were required in 82 patients. During the early years the
      incidence of complications was higher. Dislocation was the indication for 30
      further procedures in 26 patients. Thirty patients underwent 33 revision
      procedures for aseptic loosening, 12 had 29 operations because of deep infection,
      two for superficial infection, and 14 further operations were done for other
      reasons. The cumulative rate of success, without aseptic loosening, five and ten
      years after surgery, was 96% and 85%, respectively.

PMID- 11838446
TI  - From the Centers for Disease Control and Prevention. Additional options for
      preventive treatment for exposed persons to inhalational anthrax.

PMID- 11838447
TI  - From the Centers for Disease Control and Prevention. Supply diphtheria and
      tetanus toxoids and acellular pertussis vaccine.

PMID- 11838448
TI  - From the Centers for Disease Control and Prevention. Raccoon roundworm
      encephalitis--Chicago, Illinois, and Los Angeles, California, 2000.

PMID- 11838449
TI  - From the Centers for Disease Control and Prevention. Alfalfa sprouts--Arizona,
      California, Colorado, and New Mexico, February-April, 2001.

PMID- 11838450
TI  - Agents, intermediaries, and journal licensing.

PMID- 11838451
TI  - Separate paths to greatness.

PMID- 11838452
TI  - Lister Hill and his influence.

PMID- 11838453
TI  - More on Loansome Doc.

PMID- 11838454
TI  - The Brandon/Hill list.

PMID- 11838455
TI  - Proceedings, 101st annual meeting, Medical Library Association, Inc., Orlando,
      Florida, May 25-30, 2001.

PMID- 11838456
TI  - Bringing the best of medical librarianship to the patient team.
AB  - This article introduces a series of articles examining the state of the medical
      library profession as practiced in the clinical context. It is widely understood
      that many changes across the spectrum of medical librarianship practice have been
      brought about by both technological advances and economic realities. These
      changes have created strains felt by many in the profession. Discussions of
      evolving roles for medical librarians that have gone on for years have taken on a
      new sense of urgency, not just because support of library services is at stake,
      but also because new opportunities, which many are eager to explore, await
      librarians. In June 2000, an editorial appearing in a mainstream medical journal
      proposed a reinvention of clinical librarianship that, if designed as presented
      in the editorial, would have a dramatic effect on current hospital-based library
      practice. This series of articles was developed in an effort to provide
      thoughtful consideration of the "informationist" model and to present new ways to
      look at the core competencies that define the profession.

PMID- 11838457
TI  - Consumer-driven, patient-centered health care in the age of electronic
      information.
AB  - Americans are turning in increasing numbers to the Internet for information
      related to their health. Access to information that was previously difficult, if
      not impossible, for consumers to obtain has helped drive a shift in traditional
      roles for patients and physicians. Technology has made possible additional
      avenues for communication that can enhance new relationships. Ample opportunities
      exist for librarians to participate in a collaborative practice role, helping to
      serve the needs of both consumers and physicians as consumer-driven, patient
      centered health care evolves to meet its full potential.

PMID- 11838458
TI  - Hospital librarianship in the United States: at the crossroads.
AB  - This paper examines recent developments in hospital librarianship in the United
      States, including the current status of hospital-based clinical library services.
      Several examples of hospital library services are presented that demonstrate some
      characteristics of struggling and thriving services. The implications of the
      informationist concept are considered. The continuation of the hospital
      librarian's primary role in support of patient care is explored, as core
      competencies are reexamined for relevancy in the new millennium.

PMID- 11838459
TI  - Adjusting to progress: interactions between the National Library of Medicine and
      health sciences librarians, 1961-2001.
AB  - Most health sciences librarians would agree that the National Library of
      Medicine's (NLM's) leadership and its services have been highly beneficial to the
      field, but this does not prevent specific NLM actions--or lack of action--from
      being perceived as annoying or infuriating. Over the past forty years, NLM's
      interactions with health sciences librarians have been affected by significant
      additions to NLM's mission and services, the expansion of NLM's direct user
      groups, and the growing range of possible relationships between health sciences
      librarians and NLM. The greatest friction between NLM and health services
      librarians occurs when there is a fundamental change in the way NLM carries out
      its mission-a change that adds to the web of relationships that link librarians
      and NLM and prompts corresponding changes in the way other libraries do business.
      Between 1961 and 2001, there were two such fundamental changes: the
      implementation of the National Network of Libraries of Medicine and the
      development and promotion of services targeted toward individual health
      professionals. On a lesser scale, each new service that connects NLM and health
      sciences librarians is another potential source of irritation, ready to flare up
      when the service is interrupted, changed, or eliminated. Other factors--including
      strong personalities, mistakes, and poor communication--add to, but do not cause,
      the intermittent problems between NLM and its most longstanding and engaged user
      group. These problems are in essence the price we pay for the leadership and
      vision of NLM's directors and for NLM's success in developing excellent services
      and in enhancing them based on advice from librarians and other users.

PMID- 11838460
TI  - Information in context: integrating information specialists into practice
      settings.
AB  - An information need (the problem) cannot be divorced from its context. The
      problem context determines the urgency, granularity of detail, authority, and
      level of certainty required for an acceptable answer and dictates the expertise
      and resources that can be brought to bear. The size and diversity of the sources
      that can be marshalled during clinical problem solving is cognitively
      unmanageable--too large and too complex for a single person to process
      effectively in a constrained timeframe. Can the clinical team, as currently
      constituted, collectively handle this information-processing task, or is there a
      need for special information expertise on the team? If there is such a need, what
      is the best way to prepare information specialists to participate in context
      based problem solving? This article explores preparation for work in information
      rich, problem-solving environments. The authors provide two case studies, one
      clinical and one bioscientific, that elucidate knowledge and training
      requirements for information specialists who work as peers in patient care and
      research settings.

PMID- 11838461
TI  - The education of informationists, from the perspective of a library and
      information sciences educator.
AB  - This article explores the background of, and some of the current models for the
      education of, the individuals known as "informationists." A definition, an
      historical overview, and a literature review are followed by a description of the
      current practices in a variety of institutions and organizations. A series of
      five "case reports" illustrates some of the possible tracks that individuals
      seeking education as informationists may follow. A proposal for a rigorous
      planning process is made, followed by a list of recommendations for this planning
      process.

PMID- 11838462
TI  - Can the profession of pharmacy serve as a model for health informationist
      professionals?
AB  - Pharmacy could serve as a model for the health informationist profession proposed
      by Davidoff and Florance in their 2000 editorial in the Annals of Internal
      Medicine. The current training and practice roles for pharmacists suggest a way
      to prepare health sciences librarians for work with clinical health care teams.
      The influences that spurred the transformation of pharmacy parallel in many
      respects those suggesting the need for more information professionals prepared to
      practice in clinical health care settings. During the same decades that health
      sciences librarians have been debating and experimenting with new professional
      roles such as clinical medical librarians, pharmacy has undergone an intensive
      review of its core values, mission, practice roles, and educational preparation
      methods. Until recently, most pharmacists graduated from five-year baccalaureate
      programs preparing them to understand drug products, sources of supply, and
      effective ways to dispense them to patients as prescribed by physicians. Today,
      almost all pharmacy students graduate from six-year doctor of pharmacy programs
      that prepare them to be the primary providers of what their profession calls
      "pharmaceutical care." The pharmaceutical care model suggests that health
      information professionals in clinical settings could be educated and trained to
      provide what we might call health information care.

PMID- 11838463
TI  - Medical informatics education: an alternative pathway for training
      informationists.
AB  - Recognition of the growing complexity of health information needs has led to a
      call for the creation of a new health care professional, the informationist.
      Controversy exists as to the role of such individuals and what their training
      should be. A library science degree, augmented with clinical background or
      experience, is one pathway. Another to consider is training in medical
      informatics. With the right coursework, individuals trained in medical
      informatics should be equally well qualified to assume the role of
      informationists.

PMID- 11838464
TI  - The Medical Library Association: promoting new roles for health information
      professionals.
AB  - As the Medical Library Association (MLA) enters its second century, its role in
      providing leadership and focus for the education of health information
      professionals in a changing environment will be critical. MLA members face
      dramatic changes in the health care environment as well as significant
      opportunities and must position themselves to thrive in the new environment. This
      paper examines new roles for health information professionals, new approaches to
      education and training, and related issues of credentialing, certification/and
      licensure.

PMID- 11838466
TI  - Adapting a new technology to the academic medical library: personal digital
      assistants.

PMID- 11838465
TI  - Use of focus groups in a library's strategic planning process.
AB  - The use of focus groups to determine patron satisfaction with library resources
      and services is extensive and well established. This article demonstrates how
      focus groups can also be used to help shape the future direction of a library as
      part of the strategic planning process. By responding to questions about their
      long-term library and information needs, focus group participants at the
      University of Texas Southwestern Medical Center at Dallas Library contributed an
      abundance of qualitative patron data that was previously lacking from this
      process. The selection and recruitment of these patrons is discussed along with
      the line of questioning used in the various focus group sessions. Of special
      interest is the way the authors utilized these sessions to mobilize and involve
      the staff in creating the library's strategic plan. This was accomplished not
      only by having staff members participate in one of the sessions but also by
      sharing the project's major findings with them and instructing them in how these
      findings related to the library's future. The authors' experience demonstrates
      that focus groups are an effective strategic planning tool for libraries and
      emphasizes the need to share information broadly, if active involvement of the
      staff is desired in both the development and implementation of the library's
      strategic plan.

PMID- 11838467
TI  - Comprehensive weeding of an academic health sciences collection: the Briscoe
      Library experience.

PMID- 11838468
TI  - Surviving a merger: how four hospital libraries created a unified system.
AB  - Librarians are acknowledged as leaders in providing information and knowledge
      management. They recognize the importance of maintaining an awareness of the most
      cutting-edge information and technology to meet the challenges of new business
      practices and changes that inevitably occur. Working as a team, the AHS
      librarians have achieved a level of communication and cooperation that is an
      example to other departments in the system. The success of the merged libraries
      has created new opportunities for leadership and growth and an optimistic future.

PMID- 11838469
TI  - Patients waiting for elective general surgery: a culture of waiting?

PMID- 11838471
TI  - Medical devices; device tracking. Final rule.
AB  - The Food and Drug Administration (FDA) is amending the medical device tracking
      regulation. FDA is making substantive changes to revise the scope of the
      regulation and add certain patient confidentiality requirements, and
      nonsubstantive changes to remove outdated references and simplify terminology.
      These revisions are made to conform the regulation to changes made in section
      519(e) of the Federal Food, Drug, and Cosmetic Act (the act) by the FDA
      Modernization Act of 1997 (FDAMA), and to simplify certain requirements.

PMID- 11838470
TI  - The influence on treatment gain of comorbid avoidant personality disorder in
      patients with social phobia.

PMID- 11838472
TI  - Confusion in the no-clone zone.

PMID- 11838473
TI  - Stop the clock.

PMID- 11838474
TI  - Brain gain.

PMID- 11838475
TI  - Bush plans to bar firms from using gene tests.

PMID- 11838476
TI  - Modified moggies.

PMID- 11838477
TI  - The drugs don't work: TB is getting out of control as treatments languish in
      labs.

PMID- 11838478
TI  - Who's your father?

PMID- 11838479
TI  - The living dead.

PMID- 11838480
TI  - Birth of a miracle.

PMID- 11838481
TI  - Man's even better friend?

PMID- 11838482
TI  - Facing facts.

PMID- 11838483
TI  - Compassion comes before science.

PMID- 11838484
TI  - Clone encounters.

PMID- 11838485
TI  - Trust me, I'm a scientist.

PMID- 11838486
TI  - Australia stops short of a ban on therapeutic cloning.

PMID- 11838487
TI  - Regulation in the face of technological advance: who makes these calls anyway?

PMID- 11838489
TI  - Cloning and harming: children, future persons, and the "best interest" test.

PMID- 11838488
TI  - Cloning and positive liberty.

PMID- 11838490
TI  - What sort of people do we want? The ethics of changing people through genetic
      engineering.

PMID- 11838491
TI  - Why an acceptable cloning policy will be hard to achieve.

PMID- 11838492
TI  - A vote to ban cloning of human embryos.

PMID- 11838493
TI  - Reaction to President Bush's decision on embryonic stem-cell research.

PMID- 11838494
TI  - Address on federal funding of embyronic stem-cell research.

PMID- 11838495
TI  - Putting stem-cell research in perspective.

PMID- 11838496
TI  - The ethics of clinical trials: to inform or not inform? That is the question.

PMID- 11838497
TI  - Medical ethics in the Australian Defence Force.

PMID- 11838498
TI  - Should ethicists have their own code of ethics?

PMID- 11838499
TI  - Ethical issues of stereotyping.

PMID- 11838500
TI  - Fallout from the knowledge explosion: the physician as teacher in the Internet
      age.

PMID- 11838501
TI  - Religious belief, politics, and public bioethics: a challenge to political
      liberalism.

PMID- 11838502
TI  - To market, to market: cloning as an art?

PMID- 11838503
TI  - Retraction of Ruggiero and Marx (1999).

PMID- 11838504
TI  - Conducting industrial and organizational psychological research: institutional
      review of research in work organizations.
AB  - Although informed consent is a primary mechanism for ensuring the ethical
      treatment of human participants in research, both federal guidelines and American
      Psychological Association ethical standards recognize that exceptions to it are
      reasonable under certain conditions. However, agreement about what constitutes a
      reasonable exception to informed consent is sometimes lacking. We presented the
      same protocols to samples of respondents drawn from 4 populations: Institutional
      review board (IRB) members, managers, employees, and university faculty who were
      not members of IRBs. Differences in perceptions of IRB members from the other
      samples with respect to the risks of the protocols without informed consent and
      on the feasibility of conducting the research in employment organizations are
      discussed in terms of implications for industrial and organizational psychology
      research.

PMID- 11838505
TI  - Personal, practical, and professional issues in providing managed mental health
      care: a discussion for new psychotherapists.
AB  - Written by a former corporate manager pursuing counseling as a 2nd career, this
      article offers pointed views on managed mental health. Values of practitioners
      that are a mismatch for managed care are noted, and more specific disadvantages
      and advantages are examined. Loss of client confidentiality is addressed and
      procedures and technologies for its reclamation are noted. Negative effects on
      therapy are acknowledged and potential for better accountability and research are
      pointed out. Economic disadvantages of a small provider's practice as well as
      opportunities for creating new value and additional income are reviewed. The
      relatively sudden emergence of managed care is credited with a natural time lag
      preceding regulatory responses. Acknowledging that most new practitioners have
      little choice about the clients they serve, the article concludes that it would
      be shortsighted to rule managed care out of one's practice.

PMID- 11838506
TI  - Jewish and Roman Catholic approaches to access to health care and rationing.
AB  - In addressing issues of access to health care and rationing, Jewish and Roman
      Catholic writers identify similar guiding values and specific concerns. Moral
      thinkers in each tradition tend to support the guarantee of universal access to
      at least a basic level of health care for all members of society, based on such
      values as human dignity, justice, and healing. Catholic writers are more likely
      to frame their arguments in terms of the common good and to be more accepting of
      rationing that denies beneficial and needed health care to some persons. Jewish
      writers are more likely to consider individual responsibility for illness in
      allocation decisions and to accept differences in health care that different
      members of society receive. The article considers the relevance of both shared
      and complementary perspectives for deliberations in nations such as the United
      States.

PMID- 11838508
TI  - Is there a unique moral status of human DNA that prevents patenting?
AB  - The gene patenting debate, which proved to be a focal point for divergent moral
      concerns about recent developments in genome research and biotechnology, has
      revealed that the moral status of DNA is not clear. One of the arguments used to
      stop undesirable developments was that DNA possesses a unique status, which
      renders it unfit for patenting. This paper investigates the allegedly unique
      (moral) status of genetic material and the information it holds from different
      perspectives. Several properties of DNA prove to be unique. We examine the
      relevance of these for patentability of genes and conclude that only the unique
      symbolic meaning of DNA is a relevant factor, which should be taken into account
      but weighed against other interests involved.

PMID- 11838507
TI  - Parental consent and the use of dead children's bodies.
AB  - It has recently become known that, in Liverpool and elsewhere, parts of
      children's bodies were taken postmortem and used for research without the parents
      being told. But should parental consent be sought before using children's corpses
      for medical purposes? This paper presents the view that parental consent is
      overrated. Arguments are rejected for consent from dead children's interests,
      property rights, family autonomy, and religious freedom. The only direct reason
      to get parental consent is to avoid distressing the parents, which carries
      implications for the consent process, secret harvesting of body parts, and the
      weight to be given to parental feelings.

PMID- 11838509
TI  - After BIOETHICSLINE: online searching of the bioethics literature.

PMID- 11838510
TI  - A home for the National Bioethics Advisory Commission electronic archive.

PMID- 11838511
TI  - A shooting on Capitol Hill: "The Ruby Satellite System," mental illness, and
      failure of the American legal system.

PMID- 11838512
TI  - Trying to understand why horrible things happen: attribution, shame, and symptom
      development following sexual abuse.
AB  - This study concerns the nature of specific attributions for sexual abuse and
      their relation to psychological distress over time. Participants (80 children and
      57 adolescents) were seen within 8 weeks of discovery of the abuse and 1 year
      later They described why they believed the abuse happened, rated the extent to
      which internal and external attributions for the abuse event applied to them, and
      completed measures of general attribution styleforeveryday events, shame for the
      abuse, and symptoms of depression, PTSD, and self-esteem. Parents and teachers
      rated behavior problems. Abuse-specific internal attributions were consistently
      related to higher levels of psychopathology and were particularly
      importantforpredicting PTSD symptoms and parent and teacher reports of
      internalizing behavior problems, even after controlling for age, gender, abuse
      events, and general attributional style. Shame also was an important predictor of
      symptom level and mediated the relation between abuse-specific internal
      attributions and PTSD symptoms.

PMID- 11838513
TI  - Children's perceptions of their abusive experience: measurement and preliminary
      findings.
AB  - Contemporary clinical formulations and recent research highlight the importance
      of cognitive-attributional symptoms in explaining the outcomes of child abuse.
      This study is directed toward the preliminary identification and measurement of
      these attributions. From a larger sample, 47 child abuse victims (ages 6 to 18)
      were administered a 16-item interview measure designed to evaluate several
      attributions common to this population. Children and their caregivers also
      completed several other clinical measures. A priori constructs containing most
      items were formed andfound to possess internal consistency and modest stability.
      Analyses revealed the utility (e.g., differences across abuse types and
      relationships with perpetrator), criterion validity (e.g., relationship to post
      traumatic stress disorder, internalizing symptoms), and content validity (e.g.,
      professional input/ratings) of certain constructs and individual items. These
      findings identify some of the attributional sequelae of child abuse that deserve
      further clinical attention and research evaluation. Suggestions for developments
      in these two areas are discussed.

PMID- 11838514
TI  - "Explaining why": a closer look at attributions in child abuse victims.
AB  - In summary, the empirical and conceptual articles in this special issue examine
      victims' attributions from multiple perspectives, including abuse-specific, abuse
      related, and general attributions as well as attributions made by children and
      adults abused as children. The commentaries examine attributions in relation to
      treatment and in the context of a model of child abuse sequelae. Together, these
      articles examine some of the clinical/therapeutic, measurement, and scientific
      implications of this emerging topical area (e.g., what types of attributions
      merit evaluation and with what types of methods, how and when do we best modify
      maladaptive attributions, what assessment and treatment studies are needed to
      examine the role of attributions). We hope these articles will stimulate
      colleagues working with all forms maltreatment who are interested in research and
      treatment pertaining to attribution styles in childhood victims. Despite the
      complexities involved, the rewards for understanding which children are most at
      risk and for designing more effective treatments are many.

PMID- 11838515
TI  - Gender, power, and violence in the family.
AB  - Attributions for parent-child relationship outcomes were assessed as a function
      of childhood maltreatment history. In Study 1, the attributions of maltreated
      children were compared with those of nonmaltreated children from a similar
      background. Maltreated girls (but not boys) werefound to be more likely than
      nonmaltreated girls to attribute lower power or control to self than to parents.
      Effects of maltreatment on children's attributions were found for physical but
      not sexual abuse. In Study 2, the attributions of parents with a history of abuse
      as children were compared with those of parents who had not been abused. Women
      (but no men) with a history of abuse attributed less power or control to self
      than to children. Implications are drawn for gender differences in the role of
      biased attributions as a consequence of physical abuse.

PMID- 11838517
TI  - Child abuse: an attribution perspective.

PMID- 11838516
TI  - Attribution retraining with sexually abused children: review of techniques.
AB  - Clinicians increasingly use empirically based cognitive-behavioral techniques in
      their treatment of child victims of sexual abuse. Attribution retraining is often
      a primary component of this work, and it involves various techniques aimed at
      decreasing abuse-related self-blame and encouraging the child to attribute
      responsibility for the abuse to the perpetrator This article reviews literature
      that highlights the complexity of self and other blame for sexually abused
      children in terms of developmental status, the multifaceted nature and
      interrelationships of abuse-specific attributions, and the psychological effects
      of self-blame and perpetrator blame. A review of written attribution retraining
      techniques developed by diverse authors for use with sexually abused children and
      their nonoffending parents is provided, including written and verbal techniques
      and techniques using games and the arts. The relative utility of different
      approaches with children of various stages of development is discussed, along
      with the need for empirical research regarding the effectiveness of these
      techniques.

PMID- 11838518
TI  - Addressing attributions in treating abused children.

PMID- 11838519
TI  - Forensic anogenital exam interventions: potential contributions of cognitive
      appraisal theory.
AB  - This manuscript proposes that Smith and Lazarus's cognitive appraisal theory
      offers a useful conceptual guide for exploring the mechanisms underlying
      psychoeducation's apparent efficacy at reducing children's forensic anogenital
      exam distress. After presenting an overview of Smith and Lazarus's cognitive
      emotional relational theory of emotions, the authors suggest how this model of
      cognition-emotion associations might inform the refinement and evaluation of
      current preparatory interventions as well as the design of future patient/family
      education programs. Empirical evidence from the broader pediatric literature and
      direct observations of children's anogenital exam experiences suggest how
      cognitive appraisal theory translates into clinical research and practice.
      Avenues for future research are proposed.

PMID- 11838520
TI  - Attributions and adjustment following child sexual and physical abuse.
AB  - Individuals who experience child physical orsexual abuse are at greater risk for
      adjustment problems. However, the heterogeneity of symptomatology observed across
      individuals following child abuse suggests that outcome is determined by
      multiplefactors. The authors review literature examining the relationships among
      childhood physical or sexual abuse, attributions, and adjustment. Implications
      for application and future research are discussed.

PMID- 11838521
TI  - Publications by family medicine faculty in the biomedical literature: 1989-1999.
AB  - BACKGROUND AND OBJECTIVES: Concern has been expressed about a possible decrease
      in publication productivity of family medicine faculty. This study measured
      trends in publication productivity by family medicine faculty from 1989 to 1999
      and determined the journals in which these individuals published their work.
      METHODS: A sample of Society of Teachers of Family Medicine (STFM) members was
      identified from the STFM membership roster The sample included 900 members from
      1980, 1,801 members from 1994, and 1,524 members from 1999. A MEDLINE search was
      performed to determine how many articles each individual published during those
      years and in what journals the articles were published. An estimate was made of
      the total publication productivity of all STFM members. RESULTS: The percentage
      of STFM members publishing at least one article in 1989, 1994, and 1999 was 16%,
      16.3%, and 8.5%, respectively. The estimated total number of publications by all
      STFM members in all journals was 729 in 1989,1,040 in 1994, and 669 in 1999. The
      journals in which STFM members most frequently published were the Journal of
      Family Practice, Family Medicine, and Academic Medicine; 32% of all publications
      appeared in those three journals. The number of publications in high-profile
      interdisciplinary journals was very small. CONCLUSIONS: Based on a MEDLINE search
      of a large sample of STFM members' publication records, it appears that the
      publication productivity of the STFM membership is decreasing.

PMID- 11838522
TI  - Put prevention into practice (PPIP): evaluating PPIP in two family practice
      residency sites.
AB  - BACKGROUND AND OBJECTIVES: The Put Prevention Into Practice (PPIP) office system
      is a set of office tools designed to address physician, patient, and system
      barriers to the provision of clinical preventive services. This study evaluated
      the effect of using PPIP on the delivery of clinical preventive services at two
      family practice residency sites. METHODS: After a careful planning process at
      each clinic, a 1-year trial was conducted with implementation of PPIP at two
      residency sites compared to two control residency sites. The subjects included
      adults age 19 and older Data were collected via chart extraction on 300 randomly
      selected patients per clinic for the following three outcomes: health risk factor
      assessment (for limited physical activity, poor nutrition habits, and tobacco
      use), health promotion/counseling (for nutrition, physical activity, and tobacco
      use), and screening rates (clinical breast exam, cholesterol, fecal occult blood
      test, mammography, and Pap smear). RESULTS: Only inconsistent or sporadic
      differences in risk factor assessment, health promotion counseling, and screening
      were seen when comparing implementation and control sites. CONCLUSIONS: PPIP had
      little effect on the delivery of clinical preventive services. Future research
      should include a careful analysis of the users of PPIP and the environments in
      which they practice.

PMID- 11838523
TI  - Improving family practice residents' compliance with asthma practice guidelines.
AB  - OBJECTIVES: This study primarily determined the effect of an educational and
      system intervention on residents' documentation of the severity classification of
      asthma. Secondarily, the study assessed the effect of classification on
      pharmacologic treatment, as outlined by national asthma treatment guidelines.
      METHODS: We reviewed the charts of all patients with asthma seen by the residents
      in the Center for Family Medicine (CFM) between October 1, 1998, and March 31,
      1999. Data gathered from each chart included, but was not limited to, disease
      severity classification and medication regimen. Between July 1999 and October
      1999, efforts at increasing residents' knowledge of asthma severity
      classification were made via formal and informal teaching. A post-intervention
      chart review was performed on all patients with asthma seen by the residents in
      the CFM between October 1, 1999, and March 31, 2000. RESULTS: A total of 8.5% of
      198 and 51% of 271 patient visits were classified with respect to asthma severity
      in the pre- and post-intervention periods, respectively. Classified patients were
      treated appropriately 100% of the time in the pre-intervention period and 76% of
      the time in the post-intervention period. CONCLUSIONS: A comprehensive protocol
      significantly improved compliance with national asthma treatment guidelines with
      respect to severity classification but not pharmacologic treatment.

PMID- 11838524
TI  - Factors influencing immunization status in primary care clinics.
AB  - BACKGROUND AND OBJECTIVES: National standards and goals for childhood
      immunization rates are well established. Yet, despite clear standards and goals,
      physicians do not achieve the desired rate (90%) for immunization coverage. This
      study examined factors related to immunization status for 2-year-old children in
      pediatric and family practice settings. METHODS: Specially trained personnel used
      computer software to audit 2,552 records from 42 practices in Northeast Florida
      throughout 1997-1999. Immunization records were judged as either complete or
      incomplete, and factors related to immunization status were studied. Clinic type
      and 18 immunization practice standards were reviewed for effect on immunization
      status. RESULTS: The probability of complete immunization status for children in
      pediatric clinics was greater than for those in family practice clinics.
      Multivariate logistic regression revealed that use of semiannual audits (odds
      ratio [OR]=2.00, confidence interval [CI]=1.65-2.42) was the most important
      factor for immunization completion. This was followed by availability of
      discounted immunizations (OR=.44, CI=.27-.73) and the use of an immunization
      tracking system (OR= 1.48, CI= 1.18-1.70). Factors that were not found to
      contribute included clinic type and the remaining 15 practice standards.
      CONCLUSIONS: Considering the significant factors, immunization status was not
      affected by the type of clinic providing immunizations. Based on this analysis,
      family physicians should implement tracking systems and should perform semiannual
      audits to match the success of pediatricians in immunizing children. Neither
      group met nationally established goals for administration of immunizations for 2
      year-old children.

PMID- 11838525
TI  - Measuring academic production.
AB  - BACKGROUND: The entire academic medical community is under increasing pressure to
      define and measure its activities. Previous relative value-based systems to
      measure research, teaching, administration, and patient care share several
      features that threaten their acceptability and validity. Using a bottom-up
      approach, our academic family medicine department attempted to develop a
      measurement system that avoided some of the flaws of the earlier systems.
      METHODS: The system was developed in two phases. In the first phase, faculty
      members were invited to submit lists of all their professional activities. In the
      second phase, the faculty rated the relative value of a comprehensive list of
      academic activities using an unbounded ratio scale and indicated how many times a
      year they did each activity. RESULTS: Phase One resulted in a list of 96 academic
      activities. The activity rated in Phase Two as having the greatest relative value
      was principal investigator of a funded grant (relative value=30.23), followed by
      sole author of a book (relative value=28.25). The activity with the smallest
      relative value was attending a faculty meeting (relative value=.36). A half-day
      clinic session had a relative value of 1.08. The department's annual production,
      measured in relative value units, was 5,764 units of administration, 5,702 units
      of clinical activities, 5,480 units of teaching, and 4,401 units of scholarly
      activities. CONCLUSIONS: Overall, the process efficiently produced relative value
      measures for a large number of faculty activities using a process in which most
      of the faculty participated. Problems with internal coherence, face validity, and
      inconsistencies in estimation suggest it would be premature to use such estimates
      of relative value to quantify individuals 'productivity as a basis for budgetary
      decisions.

PMID- 11838526
TI  - An ounce of prevention is a ton of work.

PMID- 11838527
TI  - The state of family medicine research, or, stop, hey, what's that sound?
      Everybody look what's going down!

PMID- 11838528
TI  - Genetics of brain function and cognition.
AB  - There is overwhelming evidence for the existence of substantial genetic
      influences on individual differences in general and specific cognitive abilities,
      especially in adults. The actual localization and identification of genes
      underlying variation in cognitive abilities and intelligence has only just
      started, however. Successes are currently limited to neurological mutations with
      rather severe cognitive effects. The current approaches to trace genes
      responsible for variation in the normal ranges of cognitive ability consist of
      large scale linkage and association studies. These are hampered by the usual
      problems of low statistical power to detect quantitative trait loci (QTLs) of
      small effect. One strategy to boost the power of genomic searches is to employ
      endophenotypes of cognition derived from the booming field of cognitive
      neuroscience. This special issue of Behavior Genetics reports on one of the first
      genome-wide association studies for general IQ. A second paper summarizes
      candidate genes for cognition, based on animal studies. A series of papers then
      introduces two additional levels of analysis in the "black box" between genes and
      cognitive ability: (1) behavioral measures of information-processing speed
      (inspection time, reaction time, rapid naming) and working memory capacity
      (performance on on single or dual tasks of verbal and spatio-visual working
      memory), and (2) electrophyiosological derived measures of brain function (e.g.,
      event-related potentials). The obvious way to assess the reliability and validity
      of these endophenotypes and their usefulness in the search for cognitive ability
      genes is through the examination of their genetic architecture in twin family
      studies. Papers in this special issue show that much of the association between
      intelligence and speed-of-information processing/brain function is due to a
      common gene or set of genes, and thereby demonstrate the usefulness of
      considering these measures in gene-hunting studies for IQ.

PMID- 11838529
TI  - A genome-wide scan of 1842 DNA markers for allelic associations with general
      cognitive ability: a five-stage design using DNA pooling and extreme selected
      groups.
AB  - All measures of cognitive processes correlate moderately at the phenotypic level
      and correlate substantially at the genetic level. General cognitive ability (g)
      refers to what diverse cognitive processes have in common. Our goal is to
      identify quantitative trait loci (QTLs) associated with high g compared with
      average g. In order to detect QTLs of small effect size, we used extreme selected
      samples and a five-stage design with nominal alpha levels that permit false
      positive results in early stages but remove false positives in later stages. As a
      first step toward a systematic genome scan for allelic association, we used DNA
      pooling to screen 1842 simple sequence repeat (SSR) markers approximately evenly
      spaced at 2 cM throughout the genome in a five-stage design: (1) case-control DNA
      pooling (101 cases with mean IQ of 136 and 101 controls with mean IQ of 100), (2)
      case-control DNA pooling (96 cases with IQ > 160 and 100 controls with mean IQ of
      102), (3) individual genotyping of Stage 1 sample, (4) individual genotyping of
      Stage 2 sample, (5) transmission disequilibrium test (TDT; 196 parent-child trios
      for offspring with IQ > 160). The over all Type I error rate is 0.000125, which
      robustly protects against false positive results. The numbers of markers
      surviving each stage using a conservative allele-specific directional test were
      108, 6, 4, 2, and 0, respectively, for the five stages. A genomic control test
      using DNA pooling suggested that the failure to replicate the positive case
      control results in the TDT analysis was not due to ethnic stratification. Several
      markers that were close to significance at all stages are being investigated
      further. Relying on indirect association based on linkage disequilibrium between
      markers and QTLs means that 100,000 markers may be needed to exclude QTL
      associations. Because power drops off precipitously for indirect association
      approaches when a marker is not close to the QTL, we are not planning to genotype
      additional SSR markers. Instead we are using the same design to screen markers
      such as cSNPs and SNPs in regulatory regions that are likely to include
      functional polymorphisms in which the marker can be presumed to be the QTL.

PMID- 11838530
TI  - The genetics of cognitive processes: candidate genes in humans and animals.
AB  - It has been hypothesized that numerous genes contribute to individual variation
      in human cognition. An extensive search of the scientific literature was
      undertaken to identify candidate genes which might contribute to this complex
      trait. A list of over 150 candidate genes that may influence some aspect of
      cognition was compiled. Some genes are particularly strong candidates based on
      evidence for involvement in cognitive processes in humans, mice, and Drosophila
      melanogaster. This survey confirms that many genes are associated with cognitive
      variation and highlights the potential importance of animal models in the study
      of human cognition.

PMID- 11838531
TI  - Stability of genetic and environmental influences on P300 amplitude: a
      longitudinal study in adolescent twins.
AB  - This study examined the stability of genetic and environmental influences on
      individual differences in P300 amplitude during adolescence. The P300 component
      is an event-related brain potential (ERP) that has attracted much attention as a
      biological marker for disturbed cognitive processing in psychopathology.
      Understanding the genetics of this biological marker may contribute to
      understanding the genetics of the associated psychopathologies. In a group of 213
      adolescent twin pairs, the P300 component was measured twice, the first time at
      age 16 and the second time 18 months later. A large part of the variance of the
      P300 amplitude could be explained by familial factors, with estimates ranging
      from 30% to 81%. Whether the familial resemblance was due to genetic or shared
      environmental factors depended on sex. For males, genetic factors explained
      familial resemblance in P300 amplitude, but for females such resemblance was
      likely due to shared environmental factors. The phenotypic stability of the P300
      amplitude from 16 to 18 years was high in both sexes, and stability could be
      attributed largely to the same familial factors. There was no evidence that new
      familial influences emerged at age 18.

PMID- 11838533
TI  - Genetic influence on the variance in P3 amplitude and latency.
AB  - The P3(00) event-related potential (ERP) component is widely used as a measure of
      cognitive functioning and provides a sensitive electrophysiological index of the
      attentional and working memory demands of a task. This study investigated what
      proportion of the variance in the amplitude and latency of the P3, elicited in a
      delayed response working memory task, could be attributed to genetic factors. In
      335 adolescent twin pairs and 48 siblings, the amplitude and latency of the P3
      were examined at frontal, central, and parietal sites. Additive genetic factors
      accounted for 48% to 61% of the variance in P3 amplitude. Approximately one-third
      of the genetic variation at frontal sites was mediated by a common genetic factor
      that also influenced the genetic variation at parietal and central sites.
      Familial resemblance in P3 latency was due to genetic influence that accounted
      for 44% to 50% of the variance. Genetic covariance in P3 latency across sites was
      substantial, with a large part of the variance found at parietal, central, and
      frontal sites attributed to a common genetic factor. The findings provide further
      evidence that the P3 is a promising phenotype of neural activity of the brain and
      has the potential to be used in linkage and association analysis in the search
      for quantitative trait loci (QTLs) influencing cognition.

PMID- 11838532
TI  - Genetic correlation between the P300 event-related brain potential and the EEG
      power spectrum.
AB  - Previous studies have demonstrated moderate heritability of the P300 component of
      event-related brain potentials (ERPs) and high heritability of background
      electroencephalogram (EEG) power spectrum. However, it is unclear whether EEG and
      ERPs are influenced by common or independent genetic factors. This study examined
      phenotypic and genetic correlations between EEG spectral power and P300 amplitude
      using data from 206 Dutch twin pairs, age 16 years. Multivariate genetic models
      (Cholesky decomposition) were fitted to the observed twin covariances using Mx
      software. In males, genetic correlations between P300 and EEG power measures were
      high (0.54-0.74); 30% of the total P300 variance could be explained by genetic
      factors influencing EEG delta power and 26% by P300-specific genetic factors
      (total heritability 56%). In females, 45% of P300 variance could be attributed to
      familial influences that were shared with the EEG. However, it was not possible
      to distinguish between the genetic versus shared environmental factors,
      consistent with previous analysis of P300 in this sample (van Beijsterveldt et
      al., 1998). The results suggest that a substantial proportion of genetic
      influences on P300 amplitude can be explained by strong heritability of slow EEG
      rhythms contributing to P300.

PMID- 11838534
TI  - Are smarter brains running faster? Heritability of alpha peak frequency, IQ, and
      their interrelation.
AB  - It has often been proposed that faster central nervous system (CNS) processing
      amounts to a smarter brain. One way to index speed of CNS processing is through
      the assessment of brain oscillations via electroencephalogram (EEG) recordings.
      The dominant frequency (peak frequency) with which neuronal feedback loops in an
      adult human brain oscillate in a relaxed state is around 10 cycles/sec, but large
      individual differences exist in peak frequencies. Earlier studies have found high
      peak frequencies to be associated with higher intelligence. In the present study,
      data from 271 extended twin families (688 participants) were collected as part of
      a large, ongoing project on the genetics of adult brain function and cognition.
      IQ was assessed with the Dutch version of the Wechsler Adult Intelligence Scale
      (WAIS-IIIR), from which four dimensions were calculated (verbal comprehension,
      working memory, perceptual organization, and processing speed). Individual peak
      frequencies were picked according to the method described by Klimesch (1999) and
      averaged 9.9 Hz (SD 1.01). Structural equation modeling indicated that both peak
      frequency and the dimensions of IQ were highly heritable (range, 66% to 83%). A
      large part of the genetic variance in alpha peak frequency as well as in working
      memory and processing speed was due to nonadditive factors. There was no evidence
      of a genetic correlation between alpha peak frequency and any of the four WAIS
      dimensions: Smarter brains do not seem to run faster.

PMID- 11838535
TI  - Genetic covariance among measures of information processing speed, working
      memory, and IQ.
AB  - The genetic relationship between lower (information processing speed),
      intermediate (working memory), and higher levels (complex cognitive processes as
      indexed by IQ) of mental ability was studied in a classical twin design
      comprising 166 monozygotic and 190 dizygotic twin pairs. Processing speed was
      measured by a choice reaction time (RT) task (2-, 4-, and 8-choice), working
      memory by a visual-spatial delayed response task, and IQ by the Multidimensional
      Aptitude Battery. Multivariate analysis, adjusted for test-retest reliability,
      showed the presence of a genetic factor influencing all variables and a genetic
      factor influencing 4- and 8-choice RTs, working memory, and IQ. There were also
      genetic factors specific to 8-choice RT, working memory, and IQ. The results
      confirmed a strong relationship between choice RT and IQ (phenotypic
      correlations: -0.31 to -0.53 in females, -0.32 to -0.56 in males; genotypic
      correlations: -0.45 to -0.70) and a weaker but significant association between
      working memory and IQ (phenotypic: 0.26 in females, 0.13 in males; genotypic:
      0.34). A significant part of the genetic variance (43%) in IQ was not related to
      either choice RT or delayed response performance, and may represent higher order
      cognitive processes.

PMID- 11838536
TI  - Perceptual speed and IQ are associated through common genetic factors.
AB  - Individual differences in inspection time explain about 20% of IQ test variance.
      To determine whether the association between inspection time and IQ is mediated
      by common genes or by a common environmental factor, inspection time and IQ were
      assessed in an extended twin design. Data from 688 participants from 271 families
      were collected as part of a large ongoing project on the genetics of adult brain
      function and cognition. The sample consisted of a young adult cohort (mean age
      26.2 years) and an older adult cohort (mean age 50.4 years). IQ was assessed with
      the Dutch version of the WAIS-3R. Inspection time was measured in the so-called
      II-paradigm, in which a subject is asked to decide which leg of the II-figure is
      longest at varying display times of the II-figure. The number of correct
      inspections per second (i.e., the reciprocal of inspection time) was used to
      index perceptual speed. For Verbal IQ and Performance IQ, heritabilities were 85%
      and 69%, respectively. For perceptual speed, 46% of the total variance was
      explained by genetic variance. No differences in heritability estimates across
      age cohorts or sexes were found. Across the whole sample, a significant
      phenotypic correlation was found between perceptual speed and Verbal IQ (0.19)
      and between perceptual speed and Performance IQ (0.27). These correlations were
      entirely due to a common genetic factor that accounted for 10% of the genetic
      variance in verbal IQ and for 22% of the genetic variance in performance IQ. This
      factor is hypothesized to reflect the influence of genetic factors that determine
      axonal myelination in the central nervous system.

PMID- 11838537
TI  - Genetic influence on ERP slow wave measures of working memory.
AB  - Individual differences in the variance of event-related potential (ERP) slow wave
      (SW) measures were examined. SW was recorded at prefrontal and parietal sites
      during memory and sensory trials of a delayed-response task in 391 adolescent
      twin pairs. Familial resemblance was identified and there was a strong suggestion
      of genetic influence. A common genetic factor influencing memory and sensory SW
      was identified at the prefrontal site (accounting for an estimated 35%-37% of the
      reliable variance) and at the parietal site (51%-52% of the reliable variance).
      Remaining reliable variance was influenced by unique environmental factors.
      Measurement error accounted for 24% to 30% of the total variance of each
      variable. The results show genetic independence for recording site, but not trial
      type, and suggest that the genetic factors identified relate more directly to
      brain structures, as defined by the cognitive functions they support, than to the
      cognitive networks that link them.

PMID- 11838538
TI  - Genetic structure of spatial and verbal working memory.
AB  - Working memory (WM) encompasses both short-term memory (storage) and executive
      functions that play an essential role in all forms of cognition. In this study,
      the genetic structure of storage and executive functions engaged in both a
      spatial and verbal WM span task is investigated using a twin sample. The sample
      consists of 143 monozygotic (MZ) and 93 dizygotic (DZ) Japanese twin pairs, ages
      16 to 29 years. In 155 (87 MZ, 62 DZ) of these pairs, cognitive ability scores
      from the Kyodai Japanese IQ test are also obtained. The phenotypic relationship
      between WM and cognitive ability is confirmed (r = 0.26-0.44). Individual
      differences in WM storage and executive functions are found to be significantly
      influenced by genes, with heritability estimates all moderately high (43%-49%),
      and estimates for cognitive ability comparable to previous studies (65%). A large
      part of the genetic variance in storage and executive functions in both spatial
      and verbal modalities is due to a common genetic factor that accounts for 11% to
      43% of the variance. In the reduced sample, this common genetic factor accounts
      for 64% and 26% of the variance in spatial and verbal cognitive ability,
      respectively. Additional genetic variance in WM (7%-30%) is due to modality
      specific factors (spatial and verbal) and a storage specific factor that may be
      particularly important for the verbal modality. None of the variance in cognitive
      ability is accounted for by the modality and storage genetic factors, suggesting
      these may be specific to WM.

PMID- 11838539
TI  - Etiology of reading difficulties and rapid naming: the Colorado Twin Study of
      Reading Disability.
AB  - Children with reading deficits perform more slowly than normally-achieving
      readers on speed of processing measures, such as rapid naming (RN). Although
      rapid naming is a well-established correlate of reading performance and both are
      heritable, few studies have attempted to assess the cause of their covariation.
      Measures of rapid naming (numbers, colors, objects, and letters subtests),
      phonological decoding, orthographic choice, and a composite variable (DISCR)
      derived from the reading recognition, reading comprehension, and spelling
      subtests of the Peabody Individual Achievement Test were obtained from a total of
      550 twin pairs with a positive school history of reading problems. Basic DeFries
      and Fulker (DF) multiple regression models for the analysis of selected twin data
      confirmed the heritable nature of phonological decoding, orthographic choice,
      DISCR, and rapid-naming composites. Bivariate DF models were employed to examine
      the extent to which deficits in the three reading-related measures covary
      genetically with rapid naming. Significant bivariate heritability estimates for
      each of the reading measures with the numbers and letters rapid-naming composite
      were also obtained. As expected, univariate sib-pair linkage analyses indicated
      the presence of a quantitative trait locus (QTL) on chromosome 6p21.3 for
      phonological decoding and orthographic choice deficits. Bivariate linkage
      analyses were then conducted to test the hypothesis that this QTL for reading
      difficulties is pleiotropic for slower performance on RN tasks. The results
      obtained from these analyses did not provide substantial evidence that the 6p QTL
      for reading difficulties has significant effects on rapid naming; however, larger
      samples would be required to test this hypothesis more rigorously.

PMID- 11838540
TI  - Longitudinal genetic analysis of EEG coherence in young twins.
AB  - During middle childhood, continuous changes occur in electroencephalogram (EEG)
      coherence, an index of cortico-cortical connectivity of the brain. In the gradual
      development of EEG coher ence, occasional "growth spurts" are observed which
      coincide with periods of discontinuous development in cognition. Discontinuous
      development may reflect changes in the genetic architecture of a trait over time,
      for instance, by the emergence of new genetic factors. To examine stability and
      change in genetic and environmental influences on EEG coherence from ages 5 to 7
      years, intrahemispheric EEG coherences from 14 connections were collected twice
      in 209 twin pairs. Overall, heritabilities (h2) were moderate to high for all EEG
      coherences at both ages (average: 58%). For occipito-cortical connections in the
      right hemisphere, h2 increased with age due to a decrease in environmental
      variance. For prefronto-cortical connections in the left hemisphere, h2 decreased
      with age due to a decrease in genetic variance. New genetic factors at age 7 were
      found for prefronto-parietal coherence, and centro-occipital and parieto
      occipital EEG coherences in both hemispheres and, in the left hemisphere, for
      prefronto-frontal EEG coherences. Mean genetic correlation for these cortico
      cortical connections over time was 0.72, indicating that at least part of the
      genetic influences is age-specific. We argue that this is convincing evidence for
      the existence of stage-wise brain maturation from years 5 to 7, and that growth
      spurts in EEG coherence may be part of the biological basis for discontinuous
      cognitive development at that age range.

PMID- 11838541
TI  - Chemical carboxyl-terminal sequence analysis of peptides and proteins using
      tribenzylsilyl isothiocyanate.
AB  - A new derivatization reagent, tribenzylsilyl isothiocyanate (TBS-ITC), is applied
      to C-terminal peptide and protein sequencing. It has been successfully used to
      sequence six C-terminal residues of house apomyoglobin and a synthetic peptide at
      low nanomole levels. The chemistry involves activation with acetic anhydride,
      derivatization with TBS-ITC, and cleavage of derivatized C-terminal amino acid
      thiohydantoin with sodium hydroxide. The tribenzylsilyl is a bulky, electric
      donor group and is a good leaving group. It facilitates the nucleophilic attack
      of the NCS(-1) in the coupling reaction. The efficiency for C-terminal sequencing
      by TBS-ITC is about the same as that of acetyl isothiocyanate (AITC), which is a
      derivatizing reagent for C-terminal sequencing developed by our laboratory. TBS
      ITC is much more stable than AITC and trimethylsilyl isothiocyanate (TMS-ITC).
      TBS-ITC is a solid with relatively long shelf life, whereas AITC and TMS-ITC are
      liquid and not stable at room temperature.

PMID- 11838542
TI  - Amino acid sequence of Kalinowaski's Tinamou (Nothoprocta kalinowskii) hemoglobin
      and the rate of evolution of bird alphaD-globin.
AB  - Two hemoglobin components are recognized in erythrocytes of the adult Tinamou. We
      determined the amino acid sequences of Tinamou alphaD-, alphaA-, and beta-globins
      from intact globin chains and several chemically cleaved fragments. A remarkable
      feature of Tinamou hemoglobin was a deletion in the alphaD-globin chain. This has
      not been reported in the literature, except in pigeon embryonic alphaD-globin.
      The amino acid sequences of Tinamou globin were highly similar to those of
      Ostrich and Rhea hemoglobin. Comparison between Tinamou, Ostrich, and Rhea that
      suggested the evolution speed of globin, alphaD = alphaA > beta, was related with
      the early appearance birds. The important residues in Tinamou hemoglobin as the
      heme contact and oxygen binding regions were highly conserved in other species.

PMID- 11838543
TI  - Barley beta-galactosidase: structure, function, heterogeneity, and gene origin.
AB  - Barley (Hordeum vulgare) beta-galactosidase is composed of a large (45 kDa) and a
      small (33 kDa) polypeptide. N-terminal sequencing of the polypeptides and
      antibody reactivity data place the barley enzyme and heterodimeric plant beta
      galactosidases from jack bean, maize, and wheat in family 35 of the glycosyl
      hydrolases. Sequence analysis indicates the existence of a subfamily of genes
      coding for polypeptide precursors that are cleaved to produce the two subunits in
      heterodimeric beta-galactosidases. The heterogeneity of the barley holoenzyme is
      related, but not restricted, to the N-glycosylation of the small polypeptide.
      Both polypeptides are essential for the catalytic activity of the enzyme.

PMID- 11838544
TI  - Phosphorylation of the 24p3 protein secreted from mouse uterus in vitro and in
      vivo.
AB  - The 24p3 protein is a 25 KDa glycoprotein, having been purified from mouse
      uterine fluid. Thr54, Ser88, and Thr128/Ser129 on the protein molecule were
      predicted to be the phosphorylation site of casein kinase II, protein kinase C,
      and cAMP-dependent protein kinase, respectively. Incorporation of phosphate to
      this protein from [gamma-32P]-ATP was tested in the solution suitable for the
      three kinases. Neither casein kinase II nor cAMP-dependent protein kinase reacted
      to the 24p3 protein; however, protein kinase C demonstrated phosphorylation to
      this protein. This phosphorylation may be competing with a polypeptide segment:
      Arg79-Tyr-Trp-Ilu-Arg-Thr-Phe-Val-Pro-Ser88-Ser-Arg-Ala-Gly-Gln-Phe-Thr-Leu-Gly97
      in the 24p3 protein molecule. To support this theory, Ser88 is a phosphorylation
      site of protein kinase C on 24p3 protein. The enzyme kinetic parameter, based on
      the Michaelis-Menten equation, determined Km to be 2.96 microM in the
      phosphorylation of 24p3 protein by the kinase. Both of the phosphorylated and
      dephosphorylated form of 24p3 protein can enhance the cAMP-dependent protein
      kinase activity in vitro. In addition, this experiment will show for the first
      time that serine-phosphorylated 24p3 protein exists in mouse uterine tissue.

PMID- 11838545
TI  - Chemical deglycosylation can induce methylation, succinimide formation, and
      isomerization.
AB  - Interpretation of deglycosylation studies relies heavily on the absence of
      modifications to the polypeptide chain. We have found that by using a common
      chemical deglycosylation technique, one can effect at least three changes in a
      peptide's structure: methylation, isomerization, and ring formation. It was
      determined that the conditions of chemical deglycosylation introduce a +14 Da
      shift in the masses of our model peptides, RKDVY, RKEVY, and horseradish
      peroxidase. This shift is localized to acidic functional groups and is
      interpreted as methylation of the free carboxylates in our models. An additional
      shift in mass of -18 Da is found in the model peptide RKDVY consistent with the
      loss of water associated with succinimide ring formation in this peptide.
      Chemical treatment induced isomerization of aspartyl residues to isoaspartyl
      residues in another model peptide, tetragastrin. These results indicate that one
      should use caution when interpreting the results of chemical deglycosylation
      experiments.

PMID- 11838546
TI  - Bovine pancreatic elastase II cleaves Gln-Ile bond.
AB  - A peptidase (GICP) that cleaves the Gln-Ile bond of a peptide Gly-Ile-Asp-Val-Gln
      Ile-Tyr(T-1), a sequence in phenylalanine oxidase, was purified from bovine
      pancreas. The purified enzyme had an Mr of approximately 29,000, as determined by
      SDS-PAGE, and its N-terminal sequence was identical to that of bovine pancreatic
      elastase II. The enzyme released Gly-Ile-Asp-Val-Gln and Ile-Tyr from T-1 (Km =
      8.3 microM k(cat) = 2.1 s(-1)) and the catalytic efficiency (2.6 X 10(5) M(-1)s(
      1)) was comparable to those of elastase II from porcine pancreas and rat
      mesenteric arterial bed perfusate. The P1 site specificity of GICP toward
      oxidized insulin A and B chains suggested that major cleavage sites were the
      peptide bond at the C-terminal side of Gln, Leu, His, and Tyr residues.

PMID- 11838547
TI  - Isolation and characterization of a convulxin-like protein from Crotalus durissus
      collilineatus venom.
AB  - A convulxin (Cvx)-like protein was isolated from Crotalus durissus collilineatus
      venom by a combination of molecular exclusion and reversed-phase HPLC
      chromatographies. The molecular mass of the Cvx-like protein in the absence and
      presence of DTT was 78 kDa and 12-13 kDa, respectively. The Cvx-like protein
      consisted of two nonidentical polypeptide chains (alpha and beta). The N-terminal
      amino-acid sequences of the alpha and beta subunits were
      GLHCPSDWYAYDGHCYKIFNEEMNWED and GFCCPSHWSSYSRYCYKFFSQEMNWEDAEK, respectively,
      with both subunits having a high content of Glu, Ser, Cys, and Asp. The Cvx-like
      protein showed high homology with other venom C-type lectins, but had low
      hemagglutinating activity on intact and trypsinized erythrocytes. The Cvx-like
      protein stimulated insulin receptor phosphorylation and potentiated insulin
      secretion from isolated islets in the presence of sub- (2.8 mM) or supra
      physiological (16.7 mM) glucose concentrations. These results suggest that the
      increase in insulin secretion induced by Cvx-like protein may be mediated by a
      protein tyrosine kinase-dependent pathway and may involve other membrane
      receptors, such as GP VI or Scr family proteins.

PMID- 11838548
TI  - Regeneration of dorsal roots of spinal nerves in rats after transplantation of
      embryonic nerve tissue.

PMID- 11838549
TI  - Visual, auditory and bimodal activity in the banks of the lateral suprasylvian
      sulcus in the cat.
AB  - In addition to visually driven cells we found within the lateral suprasylvian
      visual cortex of cats a considerable number of auditory and/or bimodal cells.
      Most of the visually driven cells were direction and orientation selective with
      responses that were neither highly stimulus time locked nor very stable. Most of
      the auditory responses were also not very stable, had relatively high thresholds,
      and were readily habituated. Previous studies have suggested that populations of
      cells within the lateral suprasylvian area are specialized for the analysis of
      optic flow fields (Rauscheker et al., 1987; Sherk et al., 1995). Given that a
      remarkable proportion of cells within this area can be also driven by auditory
      stimuli, we hypothesize that the 'optic flow' model may be extended to the
      bimodal domain rather than restricted to visual clues only. This, however,
      remains to be corroborated experimentally.

PMID- 11838550
TI  - Macrophages of the human embryonic telencephalic choroid plexus.

PMID- 11838551
TI  - Post-tetanic modification of the efficiency of excitatory transmission in neural
      networks including interhemispheric connections.
AB  - This is the first report of modifiable reciprocal transcallosal monosynaptic
      excitatory connections, detected in in vivo experiments in the rat motor cortex
      by recording of multineuron activity and cross-correlation analysis. High
      frequency microstimulation of a small group of cortical neurons in one hemisphere
      was shown to alter the efficiency of transcallosal excitatory connections, and
      also altered the efficiency of ipsilateral connections in both hemispheres. Post
      tetanic changes consisted of long-term potentiation and depression. Neurons
      producing spike trains were found to have better conditions (compared with other
      neurons) for long-term potentiation of inputs converging on them. Synapses formed
      by axon collaterals of a given callosal cell on several neurons could
      simultaneously induce both long-term potentiation and long-term depression, while
      a given callosal neuron could simultaneously show long-term potentiation in some
      synapses and long-term depression in others. After microstimulation there were
      increases in the number of background-active callosal neurons, along with
      increases in the number and efficiency of transcallosal connections, while the
      number and efficiency of ipsilateral connections decreased. These data lead to
      the conclusion that ipsilateral inhibition is more effective than transcallosal
      inhibition. Microstimulation modified the pattern of initially existing
      connections between the many elements of ensembles including callosal cells in
      both hemispheres.

PMID- 11838552
TI  - The effects of antibodies against proteins of the s100 group on neuron plasticity
      in sensitized and non-sensitized snails.
AB  - The effects of antibodies to a total fraction of s100 proteins and protein s100b
      on the activity of defensive behavior command neurons LP11 and RP11 were studied
      in common snails, using non-sensitized animals and animals which had acquired
      nociceptive sensitization. In non-sensitized snails, application of antibodies
      against s100 or s100b (0.1 mg/ml) induced membrane depolarization, increased
      membrane permeability, and suppressed slow excitatory postsynaptic potentials in
      the responses of neurons to sensory stimulation. Acquisition of sensitization in
      snails in the presence of antibodies to s100 or s100b (0.1 mg/ml) led to
      significantly less marked facilitation of synaptic transmission and smaller
      increases in neuron membrane excitability than in cells of control sensitized
      animals. The difference in synaptic facilitation in the neurons of control
      sensitized snails and neurons in sensitized snails given antibody was comparable
      with the magnitude of synaptic depression due to antibody in non-sensitized
      animals. At a dose of 0.01 mg/ml, antibody had no effect on these measures of
      neuron activity. It is suggested that s100 proteins, particularly s100b, are
      involved in the mechanisms regulating excitability, the membrane potential, and
      synaptic transmission in command neurons in untrained snails, as well as in the
      mechanism of plasticity of the electrogenic membranes of nerve cells during the
      acquisition of nociceptive sensitization.

PMID- 11838553
TI  - Formation of C/EBP transcription factors and possible pathways for controlling
      their activity during learning in Helix.
AB  - Formation of a conditioned defensive reflex in the common snail is accompanied by
      activation of DNA-binding transcription factors of the C/EBP family. Incubation
      of the CNS with serotonin, which imitates the effects of conditioning, and
      stimulation of adenylate cyclase with forskolin also increase the efficiency with
      which these transcription complexes are formed. Induction of protein kinase C
      with phorbol ester had no stimulating effect on the formation of C/EBP factors.
      However, simultaneous treatment with phorbol ester and serotonin produced some
      increase in the cAMP-inducible effects on the activation of C/EBP transcription
      factors. Larger increases in the DNA-binding activity of transcription factors of
      the C/EBP family in response to stimulation of the cAMP-dependent pathway were
      seen in conditions of elevated intracellular Ca2+ concentrations (by incubation
      of the CNS with the calcium ionophore A23187 and forskolin). Thus, it is possible
      that the Ca2+ and cAMP-dependent regulatory systems converge, leading to
      increases in the efficiency of the formation of C/EBP transcription complexes,
      which may reflect the interaction of stimuli of different modalities during
      learning.

PMID- 11838554
TI  - Dose-dependence of the excitatory effects of acetylcholine on common snail
      neurons after orthodromic tetanization.

PMID- 11838555
TI  - Recovery of a motor habit after lesioning of the caudate nucleus in rats with
      different forelimb preferences.

PMID- 11838556
TI  - Function of the hypothalamo-pituitary-adrenocortical system during ontogenesis in
      rats with inherited stress-induced arterial hypertension.
AB  - The functional activity of the hypothalamo-pituitary-adrenocortical system (HPAS)
      during the development of rats with inherited stress-induced arterial
      hypertension (HSIAH rats) was compared with that in normotensive Wistar rats. In
      rats aged 2, 3, 4, 6, 8, 10, 12, and 18 weeks, competitive protein binding assays
      were used to estimate peripheral blood plasma corticosterone levels at rest and
      after 1 h of restricted mobility in mesh cylinders. Basal corticosterone levels
      and HPAS responses to stress were lower during ontogenesis in hypertensive rats
      than in Wistar rats of the same age. The exception was rats aged four weeks, when
      HSIAH rats started to develop hypertension and their HPAS was more sensitive to
      emotional stress than was the case in Wistar rats, this being associated with the
      greater reaction of the adrenals to ACTH. Decreased reactions of the HPAS to
      emotional stress in adult HSIAH rats is not associated with loss of adrenal ACTH
      sensitivity.

PMID- 11838557
TI  - Spatial organization of the thalamic projections of the striatum in the dog.

PMID- 11838558
TI  - The role of the ventrolateral nucleus of the thalamus in the switching of
      descending influences to motor activity in the rat.
AB  - Studies on rats showed that the facilitating influence of preliminary transection
      of the rubrospinal tract on recovery of motor activity and operant reflexes
      disrupted by lesioning of the red nucleus was more apparent when lesioning was
      chemical than when lesioning was electrolytic. This is due to the survival of
      cerebellothalamic fibers to the ventrolateral nucleus of the thalamus after
      chemical lesioning of the red nucleus with quinolinic acid. It was also shown
      that preliminary lesioning of the ventrolateral thalamic nucleus strongly
      hindered the switching of motor activity under the control of the corticospinal
      tract in rats subjected to section of the rubrospinal tract and lesioning of the
      red nucleus.

PMID- 11838559
TI  - Tonic organization of the inferior colliculi in the cat in conditions of
      simulated sound source motion.
AB  - Simulation of the motion of a sound source using a series of clicks with variable
      interaural delays was used to study movement effects as changes in the amplitude
      of sequential focal evoked potentials (EP) in series of EP arising in response to
      the signal. These experiments showed that a) in 25% of cases the movement effect
      depended on the direction of the simulated motion; b) the movement effect was
      better represented on the wide ipsilateral to the site of EP recording; left- and
      right-sided movement effects were identically dependent on the rate of motion; c)
      the phenomenon of the movement effect was associated with the dominance of
      contralateral afferentation compared with ipsilateral afferentation; d) the
      movement effect was accompanied by inhibitory manifestations consisting of
      suppression of monaural afferentation in conditions of binaural stimulation; e)
      marked movement effects were seen mainly in the ventrocentral part of the central
      nucleus, located very close to the positions of large multipolar neurons, while
      mild and moderate movement effects were distributed quite uniformly though the
      volume of the nucleus, following the distribution of the "basic" neurons; it is
      suggested that movement effects of different strengths are associated with
      differences in the ratios of the effectivenesses of ipsi- and contralateral
      stimulation, which depend on the properties of multipolar and "basic" neurons in
      the central nucleus of the inferior colliculus in relation to their responses to
      ipsi- and contralateral stimulation.

PMID- 11838560
TI  - Comparison of binaural release from forward masking in animals and humans.
      Electrophysiological studies.
AB  - Evoked potentials in the inferior colliculus and auditory areas of the cortex
      were studied in anesthetized guinea pigs and long-latency auditory evoked
      potentials (LAEP) were studied in waking humans using sequential binaural
      presentation of pairs of clicks--the masker and the masked signal--with a
      variable interval between them, to provide the conditions needed for the
      psychophysical phenomenon of direct forward masking. Introduction of phase
      differences between the masker and the masked signal led to decreases in
      suppression of responses to the masked signal and to faster recovery of the
      reaction types recorded. The greatest relative differences between response
      magnitudes to antiphase and synphase masked signals were seen at the beginning of
      the recovery process, and were 1.6, 1.5, and 1.4 respectively for responses from
      the inferior colliculus, auditory area of the cortex, and LAEP at stimulus
      intensities of 50-65 dB sound pressure level, differences subsequently decreasing
      to zero. There was a positive correlation between this measure and the stimulus
      intensity. The greatest differences between the time at which the recovery
      process ended for responses to antiphase and synphase masked signals were 4, 250,
      and about 2000 msec respectively for the inferior colliculus, auditory area of
      the cortex, and LAEP.

PMID- 11838561
TI  - Disinhibition as a mechanism for visual cortex neurons to tune to cross-shaped
      figures.
AB  - A discrete simulation model of a receptive field selectively responding to cross
      shaped figures, as seen in 40% of primary visual cortex neurons in the cat, was
      studied. The model was based on disinhibition of end-stop inhibition in the
      receptive field by the lateral disinhibition zone. These experiments showed that
      this mechanism can produce selective or, conversely, invariant tuning to the
      shape and orientation of cross-shaped figures and could underlie the high
      sensitivity of neurons to second-order image features.

PMID- 11838563
TI  - Relationship between infant and child mortality and fertility--an enquiry into
      goan women.
AB  - OBJECTIVE: This paper has an attempt to demonstrate the influence of childhood
      mortality on fertility behaviour of women in Goa. METHODS: The replacement effect
      of child mortality has been examined by comparing fertility behaviour of those
      who have and who have not experienced a child loss. The insurance effect has been
      studied through fertility differentials of those who perceived that the level of
      mortality has decreased in the region with the women who left it to be the
      otherwise. RESULT: It shows that the net effect of child mortality could be
      substantial. Women with personal experience of child loss and having pessimistic
      opinion about the level of mortality, produced, on an average, about two children
      more than similar women who never experienced a child loss and were optimistic
      about the level. The tendency to replace a dead child was found to cut across the
      level of literacy and religious background of women. CONCLUSION: The insurance
      effect on the other hand, was predominant among illiterate women.

PMID- 11838564
TI  - Red cell distribution width in the diagnosis of iron deficiency anemia.
AB  - OBJECTIVE: 1. To compare peripheral smear (PS) and Red cell distribution width
      (RDW) in diagnosis of Iron deficiency anemia (IDA) in various grades. 2. To study
      the changes in RDW and PS after therapy. METHODS: Children in the age group of
      six months to five years with microcytic (MCV<80fl) anemia (Hemoglobin <11 g%)
      were evaluated. Those who had received blood transfusion and /or were already on
      iron therapy were excluded. Evaluation included clinical examination, complete
      blood count (CBC), RDW estimation microscopic examination of peripheral smear,
      measurement of serum iron and transferrin saturation. Children with IDA were
      treated with oral iron for 8 weeks and PS, CBC including RDW were repeated.
      RESULT: Of the 100 children evaluated, 89 had IDA. 48% had mild, 42% had moderate
      and 10% had severe anemia. Transferrin saturation correlated with severity of
      anemia. Peripheral smear showed microcytosis and hypochromia in all cases with
      severe anemia, 61.5% and 22.5% of those with moderate and mild anemia
      respectively. RDW was suggestive of iron deficiency in 100%, 82.05% and 100% of
      patient with mild, moderate and severe anemia respectively. CONCLUSION: In the
      diagnosis of mild and moderate iron deficiency anemia, RDW had a higher
      sensitivity than PS. Red cell morphology, Hb, PCV and RDW showed significant
      improvement after iron-therapy.

PMID- 11838562
TI  - The effects of serotonin on functionally diverse isolated lamprey spinal cord
      neurons.
AB  - The experiments reported here showed that application of serotonin (5
      hydroxytryptamine, 5-HT) (100 microM) did not induce any significant current
      through the membranes of any of the spinal neurons studied (n = 62). At the same
      time, the membranes of most motoneurons and interneurons (15 of 18) underwent
      slight depolarization (2-6 mV) in the presence of 5-HT, which was not accompanied
      by any change in the input resistance of the cells. Depolarization to 10-20 mV
      occurred in some cells (3 of 18) of these functional groups, this being
      accompanied by 20-60% decreases in input resistance. The same concentration of 5
      HT induced transient low-amplitude depolarization of most sensory spinal neurons
      (dorsal sensory cells), this changing smoothly to long-term hyperpolarization by
      2-7 mV. The input resistance of the cell membranes in these cases showed no
      significant change (n = 8). Data were obtained which provided a better
      understanding of the mechanism by which 5-HT modulates the activity of spinal
      neurons. Thus, 5-HT facilitates chemoreceptive currents induced by application of
      NMDA to motoneurons and interneurons, while the NMDA responses of dorsal sensory
      cells were decreased by 5-HT. 5-HT affected the post-spike afterresponses of
      neurons. 5-HT significantly decreased the amplitude of afterhyperpolarization
      arising at the end of the descending phase of action potentials in motoneurons
      and interneurons and increased the amplitude of afterdepolarization in these
      types of cells. In sensory spinal neurons, 5-HT had no great effect on post-spike
      afterresponses. The results obtained here support the suggestion that 5-HT
      significantly modulates the activity of spinal neurons of different functional
      types. 5-HT facilitates excitation induced by subthreshold depolarization in
      motoneurons and some interneurons, facilitating the generation of rhythmic
      discharges by decreasing afterhyperpolarization. In sensory cells, 5-HT enhances
      inhibition due to hyperpolarization, suppressing NMDA currents. The differences
      in the effects of 5-HT on functionally diverse neurons are presumed to be
      associated with the combination of different types of 5-HT receptors on the
      membranes of these types of spinal neurons.

PMID- 11838565
TI  - Postasphyxial encephalopathy in preterm neonates.
AB  - OBJECTIVE: Perinatal asphyxia is an important determinant of infant neurological
      outcome. There are very few studies looking exclusively at postasphyxial
      encephalopathy in preterm neonates. METHODS: We studied the neurologic and
      sonographic abnormalities in 40 preterm babies with severe birth asphyxia during
      their hospital stay and till 3 months corrected age. RESULT: 87.5 % of the
      asphyxiated preterm babies had neonatal neurologic abnormality, compared to only
      17% of the control babies (p<0.0001). Generalised hypotonia and reduced activity
      were the commonest abnormalities (observed in 85% of asphyxiated babies) while
      depressed sensorium (60%) and seizures (35%) were seen in more severe cases.
      White matter disease (WMD-including periventricular flare, cerebral edema and
      periventricular leucomalacia) was significantly more frequent in the study cases
      (34.5% in study cases vs 7.5% in controls, p<0.0001) as was grade 3/4
      intraventricular hemorrhage(IVH) (25% in study cases vs 2.5% in controls,
      p<0.0001). There was 11 fold higher mortality among the asphyxiated babies (23
      deaths in study cases vs 2 in controls, p<0.0001). CONCLUSION: The survivors had
      a significantly higher incidence of both mild and severe neurological
      abnormalities at corrected age of 3 months among the asphyxiated babies. There
      was a good correlation between the severity of the neonatal encephalopathy as
      well as the sonographic findings and the outcome.

PMID- 11838566
TI  - Subcutaneous epinephrine vs nebulized salbutamol in asthma.
AB  - OBJECTIVE: This study was conducted to compare the efficacy of the subcutaneous
      epinephrine with nebulized salbutamol. METHODS: Fifty asthmatic children in the
      age range of 6-14 years were divided into two equal groups. Group I children were
      given subcutaneous epinephrine and Group II were nebulized with salbutamol.
      Patients were observed at 15, 20, 30, 60, 120, 180 and 240 minute intervals. Both
      the groups had comparable mean increase in peak expiratory flow rate (PEFR %)
      (Group I 27.7 +/- 0.7; Group II 28.8 +/- 0.06, p >0.05). RESULT: In Group I there
      was significant increase in systolic blood pressure, 30 minutes after the start
      of treatment, however it settled on its own by 60 minutes. CONCLUSION: Both the
      groups had satisfactory improvement in clinical parameters which continued upto 4
      hours after start of treatment. Subcutaneous epinephrine can be safely used if
      nebulizers are not available.

PMID- 11838567
TI  - Radiological evaluation of the urinary tract in children with urinary infection.
AB  - OBJECTIVE: This article in to study the association of structural abnormalities
      of the urinary tract in children with urinary tract infection (UTI) using
      ultrasound examination. METHODS: 262 children with culture proven urinary tract
      infection were studied. Antibiotics were given as per sensitivity pattern. All
      children had an ultrasound of the abdomen done within 3 weeks. A micturating
      cystourethrogram (MCU) was done in those with abnormalities of the lower urinary
      tract detected on ultrasound, as well as in those who had recurrence of
      infection, after a normal ultrasound. IVU and renal isotope scans were done in
      selected cases. RESULT: All children were followed up until one year after the
      study period. Fifty-four patients had an underlying urinary tract anomaly; 42
      were picked up by ultrasound and 12 by MCU. 22.9% of males and 15.9% of females
      had anomaly of the urinary tract. Children less than 2 years had the highest
      incidence of anomalies. CONCLUSION: Pelviureteric junction obstruction with
      hydronephrosis, vesicoureteric reflux and non-refluxing megaureter are the major
      anomalies picked up. 20% of children with urinary tract infections have an
      underlying structural abnormality of the urinary tract, three-fourth of which are
      picked up on ultrasound. An ultrasound abdomen is recommended in all children
      after the first UTI. In addition, an MCU is also indicated in all boys below 2
      years with UTI, since one-third of anomalies will be missed if only ultrasound is
      done.

PMID- 11838568
TI  - Upper respiratory tract infections.
AB  - Acute respiratory infections accounts for 20-40% of outpatient and 12-35% of
      inpatient attendance in a general hospital. Upper respiratory tract infections
      including nasopharyngitis, pharyngitis, tonsillitis and otitis media constitute
      87.5% of the total episodes of respiratory infections. The vast majority of acute
      upper respiratory tract infections are caused by viruses. Common cold is caused
      by viruses in most circumstances and does not require antimicrobial agent unless
      it is complicated by acute otitis media with effusion, tonsillitis, sinusitis,
      and lower respiratory tract infection. Sinusitis is commonly associated with
      common cold. Most instances of rhinosinusitis are viral and therefore, resolve
      spontaneously without antimicrobial therapy. The most common bacterial agents
      causing sinusitis are S. pneumoniae, H. influenzae, M. catarrhalis, S. aureus and
      S. pyogenes. Amoxycillin is antibacterial of choice. The alternative drugs are
      cefaclor or cephalexin. The latter becomes first line if sinusitis is recurrent
      or chronic. Acute pharyngitis is commonly caused by viruses and does not need
      antibiotics. About 15% of the episodes may be due to Group A beta hemolytic
      streptococcus (GABS). Early initiation of antibiotics in pharyngitis due to GABS
      can prevent complications such as acute rheumatic fever. The drug of choice is
      penicillin for 10-14 days. The alternative medications include oral
      cephalosporins (cefaclor, cephalexin), amoxicillin or macrolides.

PMID- 11838569
TI  - Fluid and electrolyte management in term and preterm neonates.
AB  - Disorders of fluid and electrolyte are common in neonates. Proper understanding
      of the physiological changes in body water and solute after birth is essential to
      ensure a smooth transition from the aquatic in utero environment. The newborn
      kidney has a limited capacity to excrete excess water and sodium and overload of
      fluid or sodium in the first week may result in conditions like necrotizing
      enterocolitis and patent ductus arteriosus. The beneficial effect of fluid
      restriction on the neonatal morbidity has been shown in multiple clinical trials.
      Simple measures like use of transparent plastic barriers, caps and socks are
      effective in reducing insensible water loss. Guidelines for the management of
      fluids according to birth weight, day of life and specific clinical conditions
      are provided in the protocols.

PMID- 11838570
TI  - Sepsis in the newborn.
AB  - Systemic infection in the newborn is the commonest cause of neonatal mortality.
      Data from National Neonatal Perinatal Database 2000 suggest that Klebsiella
      pneumoniae and Staphylococcus aureus are the commonest causes of neonatal sepsis
      in India. Two forms of clinical presentations have been identified. Early onset
      sepsis, probably related to perinatal risk factors, usually presents with
      respiratory distress and pneumonia whthin 72 hours of age. Late onset sepsis,
      related to hospital acquired infections, usually presents with septicemia and
      pneumonia after 72 hours of age. Clinical features of sepsis are non-specific in
      neonates and a high index of suspicion is required for the timely diagnosis of
      sepsis. Although blood culture is the gold standard for the diagnosis of sepsis,
      reports are available after 48-72 hours. A practical septic screen for the
      diagnosis of sepsis has been described and some suggestions for antibiotic use
      have been included in the protocols.

PMID- 11838571
TI  - Post-resuscitation management of asphyxiated neonates.
AB  - Perinatal asphyxia is one of the common causes of neonatal mortality. Data from
      National Neonatal Perinatal database suggest that perinatal asphyxia contributes
      to almost 20% of neonatal deaths in India. Failure to initiate or sustain
      respiration after birth has been defined as criteria for the diagnosis of
      asphyxia by WHO. Perinatal asphyxia results in hypoxic injury to various organs
      including kidneys, lungs and liver but the most serious effects are seen on the
      central nervous system. Levene's classification is a useful clinical tool for
      grading the severity of hypoxic ischemic encephalopathy. Good supportive care is
      essential in the first 48 hours after asphyxia to prevent ongoing brain injury in
      the penumbra region. Strict monitoring and prompt correction is needed for common
      problems including temperature maintenance, blood sugars, blood pressure and
      oxygenation. Phenobarbitone is the drug of choice for the treatment of
      convulsions.

PMID- 11838572
TI  - Management of infants with intra-uterine growth restriction.
AB  - Intra-uterine growth restriction (IUGR) and prematurity are the two causes for
      delivery of low birth weight infants. In India, IUGR contributes to almost two
      thirds of infants in this category. Poor nutritional status and frequent
      pregnancies are common pre-disposing conditions in addition to obstetric and
      medical problems during pregnancy. Growth restriction may be symmetrical or
      asymmetrical depending on the time of insult during pregnancy. The pathological
      insult in an asymmetrical IUGR occurs during the later part of the pregnancy and
      has a brain-sparing effect. Common morbidities are more frequent in <3rd
      percentile group as compared to 3rd-10th percentile group. Guidelines for
      management of IUGR neonates in these two groups have provided in the protocols.

PMID- 11838573
TI  - Minimal enteral nutrition.
AB  - Although parenteral nutrition has been used widely in the management of sick very
      low birth weight (VLBW) infants, a smooth transition to the enteral route is most
      desirable. Animal studies have shown that long periods of starvation are
      associated with mucosal atrophy and reduction of enzymatic activity. Studies have
      shown that giving small volumes of feeds frequently exerts a trophic effect on
      the gut mucosa. This concept has been termed as Minimal Enteral Nutriton (MEN).
      Clinical benefits of MEN include faster progression to full enteral feeds, lesser
      episodes of feed intolerance and reduction in hospital stay without a concomitant
      increase in the risk of necrotizing enterocolitis. MEN may be commenced in
      neonates on ventilation and total parenteral nutrition. A protocol for giving MEN
      has been described.

PMID- 11838574
TI  - Congenital adrenal hyperplasia presenting as hematuria and acute renal faliure.
AB  - We present a neonate who presented with hematuria and acute renal failure.
      Classical 21 hydroxylase deficiency was diagnosed on the basis of features of
      salt wasting, response to treatment with corticosteroids and mineralocorticoids
      and a positive ACTH stimulation test. Renal vein thrombosis secondary to
      hemoconcentration due to salt wasting was attributed as the cause of hematuria.
      Follow-up revealed clinical improvement and normalization of renal parameters.
      This is the first report of congenital adrenal hyperplasia presenting as
      hematuria and renal failure to the best of our knowledge.

PMID- 11838575
TI  - Tassier cleft no 30 (median cleft from lower lip to manubrium).
AB  - One-year-old female presented with cleft of lower lip, mandible, fissured tongue,
      absent hyoid bone, cleft of manubrium sterni, later is detected clinically by
      suprasternal bulge at suprasternal region while crying. It is radiologically
      detected by wide apart medial end of clavicle. This is extremely rare anomaly
      known as Tassier Cleft no 30.

PMID- 11838576
TI  - Biliary ascariasis.
AB  - Biliary ascariasis is a less frequent, but important complication of ascaris
      infestation, because it may cause biliary colic, pyogenic cholangitis, and
      septicemia. Early diagnosis and treatment is important to prevent these
      complications. We present here a five-year-old girl with biliary ascariasis,
      whose main complaint was abdominal pain. After giving piperazin salt, multiple
      ascaris worms were seen in the stool within 10 days. She is at the follow-up
      without any complication.

PMID- 11838577
TI  - An unusual presentation of impacted esophageal foreign body.

PMID- 11838578
TI  - Indicators for assessment of IDD.

PMID- 11838579
TI  - Animal models for inducing muscle hypertrophy: are they relevant for clinical
      applications in humans?
AB  - Muscle hypertrophy is an adaptive response to overload. Progressive resistance
      exercise (PRE) is thought to be among the best means to achieve hypertrophy in
      humans. While functional adaptations to PRE in muscles of humans are made in the
      clinic, it is difficult to evaluate hypertrophic responses and underlying
      mechanisms because the adaptations require many weeks or months before they
      become evident and there is a large variability in response to PRE among humans.
      In contrast, various animal models have been shown to induce rapid and extensive
      muscle hypertrophy and some models allow precise control of the exercise
      parameters. By examining the animal models of muscle hypertrophy and
      understanding the advantages and disadvantages of each, clinicians may be able to
      evaluate and use relevant data from these models to design new strategies for
      modification of PRE in humans. The purpose of this article is to review animal
      models that are currently used in basic research laboratories, discuss the
      hypertrophic and functional outcomes, and relate these to PRE used in the clinic.

PMID- 11838580
TI  - Skeletal muscle adaptations with age, inactivity, and therapeutic exercise.
AB  - One of the remarkable features of skeletal muscle is its adaptability. Skeletal
      muscle adaptations are characterized by modifications of morphological,
      biochemical, and molecular variables that alter the functional attributes of
      specific skeletal muscle fiber types. Skeletal muscle adaptation is diverse and
      the magnitude of change is dependent on many factors, such as activity pattern,
      age, and muscle fiber type composition. The adaptation of skeletal muscle in the
      adult population is well described. In contrast, the adaptation of skeletal
      muscle in the older population is less documented, especially in the area of
      inactivity-induced alterations. Age-related changes in skeletal muscle may play a
      significant role in the magnitude of change with inactivity and influence the
      rehabilitation process for the older adult. A consistent feature of age and
      inactivity is limb muscle atrophy and the loss of peak force and power.
      Differences exist in the rate and mechanisms of muscle wasting and in the
      susceptibility of a given fiber type to atrophy. Most likely, the rapid muscle
      wasting might be in part due to a decrease in protein synthesis coupled with an
      increased degradation. Besides the quantitative change in muscle mass, age and
      inactivity induce important qualitative changes in the structure of key skeletal
      muscle proteins that are manifested in alterations in contractile properties.
      Therefore, the purpose of this clinical commentary is to identify the major
      effects of age and inactivity on skeletal muscle structure and function, and
      discuss potential therapeutic interventions. Special emphasis will be placed on
      how alterations in muscle structure affect function and on the cellular and
      molecular mechanisms of the age-related and inactivity-induced muscle changes.

PMID- 11838581
TI  - What mechanisms contribute to the strength loss that occurs during and in the
      recovery from skeletal muscle injury?
AB  - In the workplace or on the athletic field, muscle strength can be decreased by
      50% or more following performance of a relatively few high-force, eccentric
      contractions. The strength loss can be prolonged, taking a month or more for
      complete recovery. It is important to understand the cause(s) of the strength
      loss so we can develop means of preventing or attenuating this loss. The cellular
      level mechanisms explaining the loss of strength following contraction-induced
      muscle injury remain controversial. The traditional thought is that initial
      strength loss is due solely to damage to force-bearing structures within the
      muscle, as evidenced by histopathology. In addition, inflammation in the days
      following injury is commonly thought to exacerbate the strength loss. We present
      data to the contrary. Recent data show that most of the early strength loss
      results from a failure of excitation-contraction coupling processes and that a
      slow loss of contractile protein in the days following injury prolongs the time
      for recovery.

PMID- 11838582
TI  - Muscular, skeletal, and neural adaptations following spinal cord injury.
AB  - Spinal cord injury is associated with adaptations to the muscular, skeletal, and
      spinal systems. Experimental data are lacking regarding the extent to which
      rehabilitative methods may influence these adaptations. An understanding of the
      plasticity of the muscular, skeletal, and spinal systems after paralysis may be
      important as new rehabilitative technologies emerge in the 21st century.
      Moreover, individuals injured today may become poor candidates for future
      scientific advancements (cure) if their neuromusculoskeletal systems are
      irreversibly impaired. The primary purpose of this paper is to explore the
      physiological properties of skeletal muscle as a result of spinal cord injury;
      secondarily, to consider associated changes at the skeletal and spinal levels.
      Muscular adaptations include a transformation to faster myosin, increased
      contractile speeds, shift to the right on the torque-frequency curve, increased
      fatigue, and enhanced doublet potentiation. These muscular adaptations may be
      prevented in individuals with acute paralysis and partially reversed in
      individuals with chronic paralysis. Moreover, the muscular changes may be
      coordinated with motor unit and spinal circuitry adaptations. Concurrently,
      skeletal adaptations, as measured by bone mineral density, show extensive loss
      within the first six months after paralysis. The underlying science governing
      neuromusculoskeletal adaptations after paralysis will help guide professionals as
      new rehabilitation strategies evolve in the future.

PMID- 11838583
TI  - Helicobacter pylori infection and gastric cancer.
AB  - According to several prospective controlled epidemiologic studies, the positive
      rate of H. pylori antibody was shown to be higher in the patients with gastric
      cancer than in the control group. Retrospective studies on the association
      between gastric cancer and H. pylori have been conducted in a large number of
      subjects and the results can be classified broadly into two categories, i.e.,
      findings affirming an association and others denying it. Research concerning the
      association between gastric cancer and H. pylori has achieved great progress over
      time, leading to the recognition of this relationship by the WHO. One of the
      greatest concerns is to ascertain whether the final outcome of H. pylori-induced
      gastritis may lead to gastric cancer. The onset of gastric cancer can be
      explained as being caused not only by H. pylori infection, but also by a
      combination of various factors such as food and the environment. However, the
      possibility that the occurrence of gastric cancer, like the recurrence of peptic
      ulcer, can be prevented by eradication of H. pylori has also been suggested.
      Further progress in clinical research is needed to resolve this issue.

PMID- 11838584
TI  - Logistic model analysis of neurological findings in Minamata disease and the
      predicting index.
AB  - OBJECTIVE: To establish a statistical diagnostic method to identify patients with
      Minamata disease (MD) considering factors of aging and sex, we analyzed the
      neurological findings in MD patients, inhabitants in a methylmercury polluted
      (MP) area, and inhabitants in a non-MP area. MATERIALS AND METHODS: We compared
      the neurological findings in MD patients and inhabitants aged more than 40 years
      in the non-MP area. Based on the different frequencies of the neurological signs
      in the two groups, we devised the following formula to calculate the predicting
      index for MD: predicting index = 1/(1+e(-x)) x 100 (The value of x was calculated
      using the regression coefficients of each neurological finding obtained from
      logistic analysis. The index 100 indicated MD, and 0, non-MD). RESULTS: Using
      this method, we found that 100% of male and 98% of female patients with MD (95
      cases) gave predicting indices higher than 95. Five percent of the aged
      inhabitants in the MP area (598 inhabitants) and 0.2% of those in the non-MP area
      (558 inhabitants) gave predicting indices of 50 or higher. CONCLUSION: Our
      statistical diagnostic method for MD was useful in distinguishing MD patients
      from healthy elders based on their neurological findings.

PMID- 11838585
TI  - Retroperitoneal fibrosis associated with membranous nephropathy effectively
      treated with steroids.
AB  - Corticosteroids were successfully used to treat a 66-year-old man with
      retroperitoneal fibrosis (RPF) and previously diagnosed membranous nephropathy.
      Proteinuria was noted at the age of 51 years, and membranous nephropathy was
      diagnosed by renal biopsy. Ten years later, he presented with right
      hydronephrosis and renal dysfunction, and was diagnosed as having RPF based on
      the typical diagnostic imaging findings. Steroid therapy was successful,
      resulting in improvement of the hydronephrosis and renal function. The
      hydronephrosis recurred three years later, but corticosteroids were again
      effective in improving ureteral obstruction. This was a rare case of recurrent
      RPF with membranous nephropathy in which steroid therapy was effective in
      treating pleural effusion and hypergammaglobulinemia during the clinical course.
      This case suggests that an immunological disorder is involved in the pathogenesis
      of RPF.

PMID- 11838586
TI  - Successful treatment of a case with rapidly progressive Bronchiolitis obliterans
      organizing pneumonia (BOOP) using cyclosporin A and corticosteroid.
AB  - A 60-year-old woman was suffering from acute onset and progressive respiratory
      distress. Her radiographic findings showed bilateral volume loss in her lower
      lobes and consolidation predominantly distributed in peribronchovascular areas.
      The biopsied specimens performed by video-assisted thoracoscopic surgery revealed
      prominent fibromyxoid connective tissue within the terminal respiratory
      bronchioles and the alveolar spaces along the airways without marked interstitial
      fibrosis. No relevant cause was determined, and she was diagnosed as having
      idiopathic BOOP. Although her clinical course was fulminant with a poor reaction
      to steroid therapy, simultaneous administration of cyclosporin A and
      corticosteroid elicited a rapid improvement. This case report presents the
      effectiveness of cyclosporin A in the treatment of progressive BOOP.

PMID- 11838587
TI  - Recurrent pneumonia due to persistent Chlamydia pneumoniae infection.
AB  - Two cases of recurrent pneumonia due to Chlamydia pneumoniae are described. C.
      pneumoniae was continuously detected from the nasopharynx in both patients by the
      polymerase chain reaction and/or culture even with appropriate antibiotic therapy
      during the first episode. After eradication of C. pneumoniae with long-term
      macrolide therapy, the respiratory symptoms of both patients completely
      disappeared and no relapse was observed. These data indicate that new treatment
      strategies may be necessary to eradicate the organism in patients prone to
      persistent infection.

PMID- 11838589
TI  - 1. Etiopathogenesis of necrotizing vasculitis.

PMID- 11838588
TI  - Adult T-cell leukemia (ATL) cells which express neural cell adhesion molecule
      (NCAM) and infiltrate into the central nervous system.
AB  - We encountered a patient with adult T-cell leukemia/lymphoma (ATL) which
      expressed neural cell adhesion molecule (NCAM). The tumor cells markedly
      infiltrated the central nervous system (CNS) during the course of the ATL. The
      patient died 20 months after disease onset, which was considered to be early in
      the course. During the invasion of the CNS, the surface phenotype of the
      peripheral blood ATL cells by flow cytometric analysis was CD2+, CD3+, CD4+, CD7
      , CD8-, CD16-, NCAM (CD56)+, HLA-DR-. We speculate that the infiltration of ATL
      cells into the CNS was closely related to the expression of the NCAM in this
      patient.

PMID- 11838590
TI  - 2. Role of adhesion molecules in vasculitis syndrome.

PMID- 11838591
TI  - 3. Takayasu arteritis.

PMID- 11838592
TI  - 4. Antineutrophil cytoplasmic antibody (ANCA) associated vasculitis: from
      molecular analysis to bedside.

PMID- 11838593
TI  - 5. Recent clinico-epidemiological manifestations of primary vasculitides.

PMID- 11838594
TI  - 1. Infectious diseases caused by antibiotic-resistant bacteria and their
      management.

PMID- 11838595
TI  - 2. Current tuberculosis problem in Japan and its control.

PMID- 11838596
TI  - 3. Current status of HIV infection in the AIDS Clinical Center (ACC).

PMID- 11838597
TI  - 4. Legionella pneumonia: present status in Japan.

PMID- 11838598
TI  - 5. Infectious disease surveillance designated by the Infectious Disease Control
      Law, and the situation of emerging/re-emerging infectious diseases in Japan.

PMID- 11838599
TI  - 1. Diabetes mellitus and lifestyle.

PMID- 11838601
TI  - 3. Insulin resistance and atherosclerosis.

PMID- 11838600
TI  - 2. Insulin resistance and hypertension in adolescents and adults.

PMID- 11838602
TI  - 4. Life-style related disease and adipocytes.

PMID- 11838603
TI  - Regulation of human growth hormone secretion and its disorders.
AB  - Growth hormone (GH) secretion from anterior pituitary is regulated by the
      hypothalamus and the mediators of GH actions. Major regulatory factors include GH
      releasing hormone (GHRH), somatostatin (SRIF), GH releasing peptide (ghrerin) and
      insulin-like growth factor (IGF-I). The principal physiological regulation
      mechanisms of GH secretion are neural endogenous rhythm, sleep, stress, exercise,
      and nutritional and metabolic signals. GH deficiency results from various
      hereditary or acquired causes, which may be isolated or combined with other
      pituitary hormone deficiencies. GH deficiency can be treated with recombinant
      human GH, which results in accelerating growth in children and normalization of
      intermediary metabolism in adults. GH hypersecretion mostly results from a
      pituitary tumor and causes acromegaly or gigantism. Hypersecretion of GH can be
      treated by transshenoidal surgery. Medical treatment with octreotide and analogs
      is also effective to reduce GH secretion in combination with or without the
      surgery.

PMID- 11838604
TI  - 5. Action by Ministry of Health, Labor and Welfare National Health Promotion in
      the 21st century "Health Japan 21".

PMID- 11838605
TI  - Autoimmune hepatitis accompanied by idiopathic thrombocytopenic purpura and
      Sjogren's syndrome.

PMID- 11838606
TI  - Quality of life in gastro-oesophageal reflux disease.

PMID- 11838607
TI  - Evolving epidemiology of viral hepatitis in Italy.

PMID- 11838608
TI  - Effect of Helicobacter pylori infection on gastric cell proliferation and genomic
      instability in a paediatric population of southern Italy.
AB  - BACKGROUND: The incidence of gastric cancer is high in areas with a high
      prevalence of Helicobacter pylori infection. Cell transformation and tumour
      progression occur over a long period of time and markers of genomic instability
      usually precede morphological changes. AIM: To evaluate the effect of
      Helicobacter pylori infection on cell proliferation, DNA status and oncogene
      expression in children. PATIENTS AND METHODS: Morphometric and
      immunohistochemical techniques were used to analyse DNA content, p53 and c-myc
      oncogene expression and cell proliferation on gastric biopsies of 53 children (27
      Helicobacter pylori-negative and 26 Helicobacter pylori-positive). RESULTS:
      Gastric mucosa was normal in 11% of Helicobacter pylori-positive and in 33% of
      Helicobacter pylori-negative subjects. Most children had chronic non-atrophic
      gastritis regardless of Helicobacter pylori infection, and only a minority of
      children affected by Helicobacter pylori had mild atrophic gastritis. Cell
      proliferation was significantly higher in children with Helicobacter pylori
      positive gastritis than in those with Helicobacter pylori-negative gastritis. No
      metaplasia, dysplasia, p53 overexpression or altered DNA content was found in any
      child. Interestingly, 46% of children with and 29% without Helicobacter pylori
      infection had c-myc overexpression closely related to the cell proliferation
      rate. CONCLUSION: Helicobacter pylori infection in children may coexist with a
      normal gastric mucosa, and it is not associated with genomic instability markers
      in cases of chronic gastritis.

PMID- 11838610
TI  - Detection of anti-Saccharomyces cerevisiae antibodies in Crohn's disease: is it a
      reliable diagnostic and prognostic marker?
AB  - BACKGROUND: In the past few years, serologic markers have been proposed in
      inflammatory bowel disease. Anti-Saccharomyces cerevisiae antibodies showed high
      specificity for Crohn's disease. A prognostic role for serology has also been
      hypothesised. AIMS: To evaluate anti-Saccharomyces cerevisiae antibody
      distribution in an unselected Italian inflammatory bowel disease population. To
      analyse whether anti-Saccharomyces cerevisiae antibody status (positive/negative)
      and/or anti-Saccharomyces cerevisiae antibody titres are associated with clinical
      variables and outcome measures in Crohn's disease patients. PATIENTS AND METHODS:
      A series of 299 inflammatory bowel disease patients were evaluated; serum samples
      were taken and a short clinical history was recorded. anti-Saccharomyces
      cerevisiae antibodies IgG enzyme-linked immunosorbent assay Medilab (Milan,
      Italy) kit was used in order to determine anti-Saccharomyces cerevisiae antibody
      status. RESULTS: Sensitivity, specificity and likelihood ratio for positive test
      in the differential diagnosis of inflammatory bowel disease was 59%, 89%, 8.1,
      respectively. Clinical variables significantly associated with anti-Saccharomyces
      cerevisiae antibody status in logistic regression were found to be ileal location
      (p=0.01) and earlier age at diagnosis (p<0.01). Among ileal Crohn's disease
      patients, there was a trend in concordance between anti-Saccharomyces cerevisiae
      antibody titres and higher number of surgical procedures which was not
      statistically significant applying more complex statistics. CONCLUSIONS: In an
      Italian inflammatory bowel disease population, anti-Saccharomyces cerevisiae
      antibodies status showed characteristics similar to those previously reported.
      Anti-Saccharomyces cerevisiae antibody positivity is associated with ileal
      involvement and with earlier onset of Crohn's disease.

PMID- 11838609
TI  - Gastric permeability is not increased in children colonized by CagA-positive
      strains of Helicobacter pylori.
AB  - BACKGROUND: Sucrose permeability has been used as a marker to detect gastric
      lesions in children. As CagA status of Helicobacter pylori is an important factor
      in determining the evolution of the gastric lesion, CagA-positive strains being
      more frequently associated with severe mucosal lesions, the aim of this study was
      to determine the prevalence of CagA-positive strains in Helicobacter pylori
      colonized children and to evaluate whether the sucrose permeability test might
      discriminate between colonization by CagA-positive or negative strains. PATIENTS
      AND METHODS: A series of 38 children (11.1+/-3.6 years) who required upper
      endoscopy for diagnostic purposes were included in the study. Endoscopy was
      carried out after the sucrose permeability test, and gastric biopsies were
      obtained for histologic examination, Helicobacter pylori detection by Giemsa
      staining and CLO-test, and determination of CagA status of the colonizing
      Helicobacter pylori strains by polymerase chain reaction. RESULTS: Helicobacter
      pylori was detected in 26 subjects (68.4%) and of these, 16 (61.5%) were
      colonized by CagA-positive strains. The intensity of the histologic findings was
      significantly associated with the presence of Helicobacter pylori and with CagA
      status of the infecting strains (chi2=21.2, p=0.0017). However no significant
      difference in the urinary excretion of sucrose between children not colonized and
      children with CagA- negative or positive strains was observed (0.027% [0.012
      0.035%]; 0.027% [0.016-0.047%] and 0.026% [0.016-0.038], median [range],
      respectively; Kruskal-Wallis analysis of variance F=0.75, p=0.69). CONCLUSIONS:
      These results indicate that in Chile, about 60% of the Helicobacter pylori
      infected children are colonized by CagA-positive strains, in association with
      more intense lesions of the gastric mucosa, but that gastric permeability to
      sucrose does not discriminate between colonization by CagA-negative and positive
      strains of Helicobacter pylori.

PMID- 11838611
TI  - Environmental risk factors and Crohn's disease: a population-based, case-control
      study in Spain.
AB  - BACKGROUND: The pathogenesis of inflammatory bowel disease probably involves an
      interaction between genetic and environmental factors: cigarette smoking,
      appendectomy and oral contraceptives have been the factors most frequently linked
      to its aetiology AIM: To analyse the association between known environmental risk
      factors and development of Crohn's disease in the community of Aragon, Spain.
      PATIENTS AND METHODS: A case-control, population-based study has been carried
      out. All patients diagnosed with Crohn's disease in the community of Aragon from
      1st February 1992 to 31st January 1995 were prospectively included. The Lennard
      Jones criteria were used to define the cases and selected controls among the
      healthy population matched with patients for age, sex and rural/urban habitat.
      Statistical analysis included multivariate analysis using conditional logistic
      regression, testing 38 different models. RESULTS: A total of 103 patients were
      diagnosed with Crohn's disease in Aragon from 1st February, 1992 to 31st January,
      1995. Of these 62 patients (60.2%) with Crohn's disease were smokers, compared
      with 42 (40.8%) controls (p<0.001). Cigarette smoking is considered a risk factor
      for Crohn's disease with an odds ratio of 3.09 (95% confidence interval, 1.58
      6.05). After multivariate analysis, the positive association is maintained. A
      dose-dependent relation could not be demonstrated. No statistical differences
      (p=0.50) were detected in the analysis of previous appendectomy. Use of oral
      contraceptive acts as a risk factor with a p=0.048; odds ratio 2, 8, 95%
      confidence interval: 1.009-7.774; but this association disappears in the
      multivariate analysis. Eight patients had a family history (3 first degree and 5
      second degree relatives) versus none of the controls (p=0.002). Of the variables
      studied for childhood hygiene none appeared significant. CONCLUSION: Smoking,
      family history, and oral contraceptive use, appear as risk factors for developing
      Crohn's disease in univariate analysis, but only smoking remains significant in
      all models of multivariate analysis.

PMID- 11838612
TI  - Liver inflammatory cells, apoptosis, regeneration and stellate cell activation in
      non-alcoholic steatohepatitis.
AB  - BACKGROUND: The pathogenesis of non-alcoholic steatohepatitis remains unclear
      from several points of view. Minimal diagnostic criteria are still not defined.
      AIM: To gather information useful for diagnosis and to improve the understanding
      of pathogenic mechanisms. PATIENTS: A series of 14 patients with non-alcoholic
      steatohepatitis, identified among liver outpatients, were paired for age, sex and
      alanine amino transferase values with 14 patients with hepatitis C virus
      infection without steatosis. METHODS: Clinical, biochemical and
      immunohistological examination, including characterisation of inflammatory cell
      population, evaluation of type III collagen and tenascin deposition, activation
      of stellate cells, hepatocellular apoptosis and proliferation. RESULTS: Patients
      with non-alcoholic steatohepatitis were more frequently obese, had higher
      triglyceride concentrations and lower gamma-globulins. T lymphocytes outnumbered
      polymorphonuclear cells, both in hepatitis C and in steatohepatitis, with a
      larger number of CD8 lymphocytes in patients with viral hepatitis but a
      comparable number of granulocytes. This resulted in a higher granulocytes to T
      cells ratio in steatohepatitis, possibly making these cells more easily
      detectable in spite of similar absolute numbers. Portal fibrosis and piecemeal
      necrosis were prevalent in hepatitis C virus infection, pericentral fibrosis was
      similar Hepatocellular apoptosis and proliferation as well as stellate cell
      activation were less relevant in steatohepatitis than in hepatitis C virus
      infection in spite of similar alanine amino transferase levels. CONCLUSIONS:
      These data provide a possible explanation for the relatively low tendency to
      progression of non-alcoholic steatohepatitis in most patients despite increased
      alanine amino transferase and suggest that non-death-related release of alanine
      amino transferase might occur in non-alcoholic steatohepatitis. This makes liver
      biopsy an essential part of the clinical setting supporting diagnosis, evaluation
      of severity and possibly definition of the evolutionary trend.

PMID- 11838614
TI  - Cronkhite-Canada syndrome. A case of sustained partial-remission.
AB  - A case of Cronkhite-Canada syndrome is described. Few cases have been published
      and in most patients the prognosis is poor. A variety of medical measures have
      been attempted in those in whom remission has been reported. In the patient
      presented here, a sustained partial-remission has been achieved with steroids.

PMID- 11838613
TI  - Changing epidemiology of parenterally transmitted viral hepatitis: results from
      the hepatitis surveillance system in Italy.
AB  - BACKGROUND: In 1991, compulsory hepatitis B virus vaccination and screening for
      anti-hepatitis C virus of blood banks were introduced in Italy. AIM: To evaluate
      the impact of preventive measures on the incidence and risk factors for
      parenterally transmitted viral hepatitis. METHODS: Data from the surveillance
      system for acute viral hepatitis for the period 1985-99 were used. Temporal
      trends in distribution of reported risk factors were analysed by comparing three
      year periods: 1987-89 and 1997-99. RESULTS: The incidence (no. cases per 100,000
      population) of hepatitis B was 12 in 1985 and 3 in 1999; the incidence of
      hepatitis non-A, non-B decreased from 5 to 1 in the same period. These decreases
      were more evident among young adults and before rather than after 1991. Multiple
      sexual partners, other parenteral exposures and dental treatment remain the most
      common risk factors for parenterally transmitted viral hepatitis. An increase in
      frequency over time was observed for other parenteral exposures, whereas a marked
      decrease was evident for blood transfusion and household contact with an HB-sAg
      carrier. Invasive medical procedures continue to represent an important source of
      infection. Intravenous drug use was reported particularly by young adults with
      non-A, non-B hepatitis, with increased frequency over time. CONCLUSIONS: Non
      immunologic measures for preventing hepatitis B and non-A, non B due to
      iatrogenic and other parenteral exposures, combined with hepatitis B virus
      vaccination, could further reduce parenteral transmission.

PMID- 11838615
TI  - Helicobacter pylori: diseases, tests and treatment.
AB  - Gastroduodenal disease associated with Helicobacter pylori infection are reviewed
      as well as the diagnostic approach. Generally, there are by and large two ways in
      which a diagnosis of infection by Helicobacter pylori can be made: by using
      either an invasive or non-invasive procedure. The invasive procedures involve
      endoscopy and biopsy Biopsy is essential since the mucosa may often appear
      macroscopically normal but, nevertheless, be inflamed. Once a biopsy is obtained
      histological examination, culture, polymerase chain reaction, detection of the
      presence of urease activity can be detected. The non-invasive tests that can be
      used to diagnose the infection are: serology, detection of labelled metabolic
      products of urea hydrolysis either in the breath (13CO2, 14CO2), the urine or the
      blood, detection of Helicobacter pylori antigen in stool specimen. At present, no
      single test is sufficiently reliable to definitely detect colonisation by
      Helicobacter pylori, and a combination of two is recommended, if feasible. Choice
      of the test to be used is not straightforward and relies on a series of
      situations, i. e., clinical setting and local expertise and availability, that
      the clinician must consider to obtain the best diagnostic yeld. The challenge of
      Helicobacter pylori eradication is not very easy to obtain. The possible scenario
      and the use of a new proton pump inhibitor (esomeprazole) are reviewed and
      discussed.

PMID- 11838617
TI  - Does helicobacter pylori eradication prevent gastric cancer?

PMID- 11838616
TI  - Risk management of HBsAg or anti-HCV positive healthcare workers in hospital.
AB  - Recommendations are made for controlling the transmission of the hepatitis B and
      hepatitis C viruses from healthcare workers to patients. These recommendations
      were based both on the literature and on experts' opinions, obtained during a
      Consensus Conference. The quality of the published information and of the
      experts' opinions was classified into 6 levels, based on the source of the
      information. The recommendations can be summarised as follows: all healthcare
      workers must undergo hepatitis B virus vaccination and adopt the standard
      measures for infection control in hospitals; healthcare workers who directly
      perform invasive procedures must undergo serological testing and the evaluation
      of markers of viral infection. Those found to be positive for: 1) HBsAg and
      HBeAg, 2) HBsAg and hepatitis B virus DNA, or 3) anti-hepatitis C virus and
      hepatitis C virus RNA must abstain from directly performing invasive procedures;
      no other limitations in their activities are necessary. Infected healthcare
      workers are urged to inform their patients of their infectious status, although
      this is left to the discretion of the healthcare worker; whose privacy is
      guaranteed by law. If exposure to hepatitis B virus occurs, the healthcare worker
      must undergo prophylaxis with specific immunoglobulins, in addition to
      vaccination.

PMID- 11838618
TI  - Gastric angiodysplasia associated with sarcoidosis.

PMID- 11838619
TI  - Helicobacter pylori eradication: do we have another ace up our sleeve?

PMID- 11838620
TI  - Open-label topiramate as primary or adjunctive therapy in chronic civilian
      posttraumatic stress disorder: a preliminary report.
AB  - BACKGROUND: The hypothesis that exposure to traumatic events may sensitize or
      kindle limbic nuclei has led to efforts to treat posttraumatic stress disorder
      (PTSD) with anticonvulsants. Based on the kindling hypothesis of PTSD, this open
      label study assesses clinical response to topiramate as a potential treatment for
      DSM-IV PTSD. METHOD: A naturalistic data review was conducted of medical records
      of all adult outpatients (9 men. 26 women symptomatic for a mean +/- SD of 18 +/-
      15 years with DSM-IV chronic civilian PTSD) treated with topiramate, 12.5 to 500
      mg/day, as add-on (N = 28) or monotherapy (N = 7). The last 17 patients completed
      the PTSD Checklist-Civilian Version (PCL-C) before treatment and at week 4.
      Dosage titration started at 12.5 to 25 mg/day and increased in 25- to 50-mg
      increments every 3 to 4 days until a therapeutic response was achieved or the
      drug was no longer tolerated. The mean duration of treatment was 33 weeks (range,
      1-119 weeks). RESULTS: Topiramate decreased nightmares in 79% (19/24) and
      flashbacks in 86% (30/35) of patients, with full suppression of nightmares in 50%
      and of intrusions in 54% of patients with these symptoms. Nightmares or
      intrusions partially improved in a median of 4 days (mean = 11 +/- 13 days) and
      were fully absent in a median of 8 days (mean = 35 +/- 49 days). Response was
      seen in 95% of partial responders at a dosage of 75 mg/day or less, and in 91% of
      full responders at a dosage of 100 mg/day or less. Mean reductions in PCL-C score
      from baseline to week 4 were highly significant (baseline score = 60 vs. week 4
      score = 39, p < .001), with similar reductions in reexperiencing, avoidance, and
      hyperarousal criteria symptoms. Thirteen patients discontinued for various
      reasons during the > 2-year study period. Except for a single instance of acute
      secondary narrow-angle glaucoma, there were no serious side effects. CONCLUSION:
      Topiramate appeared effective as add-on or monotherapy for chronic PTSD. It
      demonstrated a rapid onset of action and minimally serious, dose-related side
      effects without the development of tolerance. Double-blind studies are indicated.

PMID- 11838621
TI  - Obsessive-compulsive hoarding: symptom severity and response to multimodal
      treatment.
AB  - BACKGROUND: Compulsive hoarding and saving symptoms, found in many patients with
      obsessive-compulsive disorder (OCD), are part of a clinical syndrome that has
      been associated with poor response to medications and cognitive-behavioral
      therapy (CBT). We sought to determine whether patients with the compulsive
      hoarding syndrome had more severe symptoms and functional impairment than
      nonhoarding OCD patients and whether they would respond to intensive, multimodal
      treatment previously found to be effective for treatment-refractory OCD. METHOD:
      We studied 190 consecutive patients with DSM-IV OCD treated openly for
      approximately 6 weeks with intensive CBT, medication, and psychosocial
      rehabilitation in a partial hospitalization program for severely ill OCD
      patients. Twenty of the 190 patients (11%) were identified as having the
      compulsive hoarding syndrome. All patients were assessed before and after
      treatment with the Yale-Brown Obsessive Compulsive Scale (YBOCS), Hamilton Rating
      Scale for Depression (HAM-D). Hamilton Rating Scale for Anxiety (HAM-A). and
      Global Assessment Scale (GAS). We compared the symptom severity and response to
      treatment of compulsive hoarders versus nonhoarding OCD patients. RESULTS:
      Compulsive hoarders were significantly older than nonhoarders (p < .001).
      Hoarders had significantly lower GAS scores and higher HAM-A scores than
      nonhoarders both before (p = .04) and after (p = .002) treatment, but had similar
      pretreatment YBOCS scores. Both groups improved significantly with treatment as
      assessed by YBOCS score (p < .001), but nonhoarders had significantly greater
      decreases in YBOCS scores than hoarders (p = .02). CONCLUSION: While the
      compulsive hoarding syndrome appears to be a distinct, more disabling, variant of
      OCD that does not respond as robustly to treatment, it may still improve
      significantly with intensive, multimodal treatment tailored to its specific
      features and associated deficits.

PMID- 11838622
TI  - An open-label trial of sibutramine in obese patients with binge-eating disorder.
AB  - BACKGROUND: Binge-eating disorder was recently included in Appendix B of the
      Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV).
      Binge-eating disorder is a common diagnosis among patients who seek treatment for
      obesity. There are scant data about the efficacy of the novel antiobesity agents
      for binge-eating disorder. The objective of this article is to present data from
      an open-label study of the efficacy and tolerability of sibutramine in a group of
      obese binge eaters. METHOD: Ten obese patients with DSM-IV binge-eating disorder
      and no medical comorbidity were consecutively selected from individuals seeking
      treatment for obesity in our clinic. Treatment with sibutramine, 15 mg/day, was
      administered for 12 weeks. The number of days with binge episodes per week, the
      number of binge episodes per week, the Binge Eating Scale (BES), the Beck
      Depression Inventory, and body weight evaluation were employed for outcome
      assessment. RESULTS: Seven patients completed the trial. They showed a complete
      resolution of binge-eating disorder with no binge-eating episodes at the end of
      the treatment. The mean +/- SD number of days with binge episodes per week
      changed significantly from 5.2 +/- 1.8 at baseline to 0.8 +/- 1.9 at the end of
      the study (p < .001), and the mean BES score fell from 31.2 +/- 6.2 to 15.2 +/-
      8.2. There was a reduction of body weight (mean = 4.0 kg [8.9 lb]) from baseline
      to the end of the study. No serious adverse effects were observed. CONCLUSION:
      Sibutramine might be an effective and well-tolerated agent in the treatment of
      binge-eating disorder in obese patients.

PMID- 11838623
TI  - Reboxetine, a selective norepinephrine reuptake inhibitor, is an effective and
      well-tolerated treatment for panic disorder.
AB  - BACKGROUND: Tricyclic antidepressants and selective serotonin reuptake inhibitors
      (SSRIs) as well as benzodiazepines have been shown to be effective for the
      treatment of panic disorder. The introduction of SSRIs has enabled a greater
      understanding of the role of serotonin in the etiology of panic disorder;
      however, the role of norepinephrine has been more challenging to ascertain. The
      aim of this study was to determine the efficacy and tolerability of reboxetine, a
      novel selective norepinephrine reuptake inhibitor, in patients with panic
      disorder with and without agoraphobia. METHOD: Eighty-two patients (aged 18-65
      years) with DSM-III-R panic disorder, with or without agoraphobia, were randomly
      assigned to receive 6 to 8 mg/day of reboxetine (42 patients) or placebo (40
      patients) for 8 weeks in this placebo-controlled, parallel-group, double-blind
      clinical trial. RESULTS: Of the 82 patients enrolled in the trial, 75 were
      considered in the analysis (37 patients in the reboxetine group and 38 patients
      in the placebo group). At last assessment, there was a significant reduction in
      the mean number of panic attacks (range, 9.3-1.2) and phobic symptoms (range, 8.1
      3.2) in the reboxetine group compared with the placebo group (ranges, 8.5-5.8 and
      7.7-5.2, respectively; p < .05). Improvement in Hamilton Rating Scale for
      Depression, Hopkins Symptom Checklist-90, and Sheehan Disability Scale scores
      were also greater in the reboxetine group compared with the placebo group.
      Adverse events reported more frequently with reboxetine than placebo included dry
      mouth (36% vs. 16%), constipation (27% vs. 22%), and insomnia (26% vs. 22%).
      CONCLUSION: Reboxetine was effective and well tolerated in the treatment of panic
      disorder.

PMID- 11838624
TI  - Comparative efficacy of SSRIs and amisulpride in burning mouth syndrome: a single
      blind study.
AB  - INTRODUCTION: Although a significant amount of evidence indicates the efficacy of
      some antidepressants in treating psychogenic pain and somatoform disorder, very
      few studies have investigated their possible therapeutic action in burning mouth
      syndrome (BMS). The purpose of this 8-week, single-blind study was to provide
      preliminary data on the efficacy and tolerability of amisulpride and the
      selective serotonin reuptake inhibitors (SSRIs) paroxetine and sertraline for
      patients with BMS. METHOD: Seventy-six patients with BMS (diagnosed according to
      the criteria in the literature and integrating the Diagnostic Interview Schedule
      Revised for a complete psychiatric assessment), with no possible local or
      systemic causes and without concurrent major depression, were randomly assigned
      to receive amisulpride (50 mg/day), paroxetine (20 mg/day), or sertraline (50
      mg/day). Efficacy assessments included a visual analogue scale (VAS) for pain
      intensity, the Hamilton Rating Scale for Depression (HAM-D), the Hamilton Rating
      Scale for Anxiety (HAM-A), and the Clinical Global Impressions scale (CGI).
      RESULTS: All 3 treatment regimens resulted in a significant improvement from
      baseline in burning mouth symptoms at week 8 as demonstrated by the quantitative
      (mean reduction in VAS, HAM-D, and HAM-A scores) and qualitative (percentage of
      responders) analyses. Amisulpride showed a shorter response latency than the
      SSRIs. No serious adverse events were reported, and the incidence of side effects
      did not differ among the 3 groups. None of the patients who received amisulpride
      withdrew from the trial, whereas withdrawal from the trial occurred within the
      first week of treatment in 11.5% of patients (N = 3) treated with paroxetine and
      in 21.7% of patients (N = 5) treated with sertraline. CONCLUSION: The data
      suggest that amisulpride and SSRIs may be effective treatments for BMS; they are
      equally effective and equally well tolerated in the short-term treatment of BMS.
      Amisulpride is associated with better compliance within the first week of
      treatment and with a shorter response latency in comparison with SSRIs. This
      finding may indicate that amisulpride is especially useful at the beginning of
      drug therapy of BMS. Double-blind, placebo-controlled trials are needed to
      further document the efficacy of amisulpride and SSRIs in the treatment of BMS.

PMID- 11838625
TI  - An open-label study of citalopram in the treatment of pathological gambling.
AB  - BACKGROUND: This study evaluated the effectiveness of citalopram in the treatment
      of pathological gambling. METHOD: Fifteen adult pathological gamblers (DSM-IV
      criteria) were administered citalopram in an open-label fashion for up to 12
      weeks. Subjects were rated at baseline and at 2-week intervals on measures of
      gambling severity and depression, and monthly on quality of life. RESULTS:
      Patients reported significant (p < .05) improvements on all gambling measures
      including the number of days gambled, the amount of money lost gambling,
      preoccupation with gambling, and urges to gamble. Thirteen (86.7%) of the
      patients were rated as "much improved" or "very much improved" on a clinician
      rated Clinical Global Impressions scale for gambling. Patients reported
      improvement in depression and overall quality of life. Patients with major
      depressive disorder (MDD) (N = 8) improved to approximately the same degree as
      patients without MDD (N = 7). For most patients, clinical improvement occurred
      during the first 2 weeks of treatment; for the 9 patients who completed the
      entire 12-week trial, these gains were maintained. CONCLUSION: Citalopram appears
      to be an effective treatment for pathological gambling, and this benefit was
      independent of its antidepressant properties. Future studies employing a control
      group will be important to examine the extent of the response to nonspecific
      factors of treatment.

PMID- 11838626
TI  - Attitudes toward antipsychotics among outpatient clinic attendees with
      schizophrenia.
AB  - BACKGROUND: A cross-sectional study was conducted in patients with schizophrenia
      who regularly attended an outpatient clinic to examine the impact of
      psychopathology, side effects, and sociodemographic factors on attitudes toward
      antipsychotics. METHOD: Sixty patients with a schizophrenic disorder according to
      ICD-10 criteria who had a duration of illness over 1 year and whose discharge
      from an inpatient unit had been at least 6 weeks earlier were investigated. Apart
      from the registration of demographic data, various rating scales were used: the
      Positive and Negative Syndrome Scale, the St. Hans Rating Scale for
      Extrapyramidal Syndromes, the Udvalg for Kliniske Undersogelser (UKU) Side Effect
      Rating Scale, and the Drug Attitude Inventory (DAI). RESULTS: Generally, the
      aspects describing a positive attitude toward antipsychotics on the DAI received
      a higher degree of assent than those characterizing a negative drug attitude.
      However, employment status correlated with a poorer global medication attitude on
      the DAI, and positive symptoms and sedation correlated with greater negative
      feelings on the DAI subjective negative feelings subscale. CONCLUSION: Our
      results suggest that special attention should be paid to patients who experience
      positive symptoms or sedation and to those with relative absence of symptoms, who
      are therefore tempted to stop taking medication.

PMID- 11838627
TI  - Vitamin B6 as add-on treatment in chronic schizophrenic and schizoaffective
      patients: a double-blind, placebo-controlled study.
AB  - BACKGROUND: Vitamin B6, or pyridoxine, plays an intrinsic role in the synthesis
      of certain neurotransmitters that take part in development of psychotic states.
      Several reports indicate that vitamin B6 may be a factor in a number of
      psychiatric disorders and related conditions, such as autism, Alzheimer's
      disease, hyperactivity, learning disability, anxiety disorder, and depression.
      Moreover, there are anecdotal reports of a reduction in psychotic symptoms after
      vitamin B6 supplementation of psychopharmacologic treatment of patients suffering
      from schizophrenia or organic mental disorder. The aim of this study was to
      examine whether vitamin B6 therapy influences psychotic symptoms in patients
      suffering from schizophrenia and schizoaffective disorder. METHOD: The effects of
      the supplementation of vitamin B6 to antipsychotic treatment on positive and
      negative symptoms in 15 schizophrenic and schizoaffective patients (DSM-IV
      criteria) were examined in a double-blind, placebo-controlled, crossover study
      spanning 9 weeks. All patients had stable psychopathology for at least 1 month
      before entry into the study and were maintained on treatment with their prestudy
      psychoactive and antiparkinsonian medications throughout the study. All patients
      were assessed using the Positive and Negative Syndrome Scale (PANSS) for
      schizophrenia on a weekly basis. Patients randomly received placebo or vitamin
      B6, starting at 100 mg/day in the first week and increasing to 400 mg/day in the
      fourth week by 100-mg increments each week. RESULTS: PANSS scores revealed no
      differences between vitamin B6- and placebo-treated patients in amelioration of
      their mental state. CONCLUSION: Further studies with larger populations and
      shorter duration of illness are needed to clarify the question of the possible
      efficacy of vitamin B6 in treatment of psychotic symptoms in schizophrenia.

PMID- 11838628
TI  - Posttraumatic stress disorder and quality of life: results across 64 weeks of
      sertraline treatment.
AB  - OBJECTIVE: The goal of the current study was to characterize the quality of life
      (QOL) and functional impairment associated with posttraumatic stress disorder
      (PTSD) and to report the QOL/functional response over the course of long-term
      treatment. METHOD: QOL and psychosocial functioning were analyzed in 359 randomly
      assigned patients across a 3-phase study of sertraline in the treatment of
      chronic DSM-III-R-defined PTSD: (1) 12 weeks of double-blind, placebo-controlled
      acute treatment with sertraline in flexible doses of 50 to 200 mg/day, (2) 24
      weeks of open-label continuation treatment with sertraline among all study
      completers (regardless of initial study drug assignment or endpoint responder
      status), and (3) 28 weeks of double-blind, placebo-controlled maintenance
      treatment with sertraline in continuation phase responders. Assessments included
      the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), emotional
      role functioning and mental health subscales of the Medical Outcomes Study 36
      Item Short Form Health Survey (SF-36), as well as the occupational and social
      functioning items on the Clinician-Administered PTSD Scale, Part 2 (CAPS-2).
      RESULTS: At acute phase baseline, QOL was significantly impaired as reflected by
      a mean Q-LES-Q score of 56% of the total possible score and a CAPS-2
      social/occupational impairment composite score of 4.4. Sertraline treatment was
      associated with marked improvement on all QOL/functional measurements: at the end
      of the acute treatment phase, 58% of responders on treatment with sertraline had
      achieved Q-LES-Q total scores within 10% of community norms. Twenty-four weeks of
      continuation treatment led to an additional 20% improvement in QOL and measures
      of functioning. Double-blind discontinuation of sertraline resulted in recurrence
      of PTSD symptoms and a worsening of QOL and functional measures, although the
      degree of exacerbation in symptomatology and psychosocial impairment was notably
      less than at study entry. CONCLUSION: Sertraline treatment of chronic PTSD is
      associated with rapid improvement in quality of life that is progressive and
      sustained over the course of more than 1 year of treatment.

PMID- 11838629
TI  - A randomized, double-blind, fixed-dose comparison of paroxetine and placebo in
      the treatment of generalized social anxiety disorder.
AB  - BACKGROUND: This multicenter, double-blind, placebo-controlled study was carried
      out to determine the effectiveness and safety of various daily dosages of
      paroxetine for the treatment of generalized social anxiety disorder. METHOD: A 1
      week, single-blind, placebo run-in was followed by 12 weeks of double-blind
      treatment. 384 eligible patients meeting DSM-IV criteria for social anxiety
      disorder were randomly assigned to receive paroxetine, 20 (N = 97), 40 (N = 95),
      or 60 mg (N = 97), or placebo (N = 95) once daily in a 1:1:1:1 ratio. Primary
      efficacy variables included mean change from baseline in the Liebowitz Social
      Anxiety Scale (LSAS) total score and proportion of patients exhibiting a
      therapeutic response (defined as a Clinical Global Impressions-Global Improvement
      scale [CGI-1] score of 1 or 2). RESULTS: In the last-observation-carried-forward
      analyses, patients treated with paroxetine, 20 mg/day, had significantly greater
      improvement on mean LSAS total scores compared with those receiving placebo (p <
      .001), while the incidence of responders, based on the CGI-I rating, was
      significantly greater with paroxetine, 40 mg/day, than with placebo (p = .012).
      Patients treated with paroxetine, 20 and 60 mg, also had significantly better
      responses on the social item of the Sheehan Disability Scale than did patients
      treated with placebo (p < .019). The completer analyses showed a significant
      difference between the placebo group and the 20-mg and 40-mg paroxetine groups on
      LSAS total score and rate of response (p < or = .006). There were no serious
      adverse experiences attributed to paroxetine treatment. CONCLUSION: Paroxetine,
      20 mg/day, is an effective and safe treatment for patients with generalized
      social anxiety disorder and significantly improves social anxiety, avoidance of
      social interactions, social disability, and overall clinical condition. Further
      data analyses are needed to determine whether more specific guidelines for
      paroxetine dosage escalation in social anxiety disorder can be drawn.

PMID- 11838630
TI  - The psychopharmacology of energy and fatigue.
AB  - ISSUE: Second only to depressed mood itself tiredness, low energy, and
      listlessness are the most common symptoms associated with depression. Recent
      understanding of interactions between monoaminergic neurons may help explain why
      some antidepressants may be more rapidly energy restoring than others.

PMID- 11838631
TI  - Valproate-induced parkinsonism in a demented elderly patient.

PMID- 11838632
TI  - Hyperinsulinemia in psychiatric patients treated with olanzapine.

PMID- 11838633
TI  - No complications with risperidone treatment before and throughout pregnancy and
      during the nursing period.

PMID- 11838634
TI  - The clinical features of bipolar depression.

PMID- 11838635
TI  - Hemodialysis in the treatment of valproic acid overdose.

PMID- 11838636
TI  - Inhibition of MAPK activity, cell proliferation, and anchorage-independent growth
      by N-Ras antisense in an N-ras-transformed human cell line.
AB  - Mammalian ras genes encode a family of plasma membrane-bound proteins that
      function as intermediates in signal transduction pathways involved in cell growth
      and differentiation. Ras oncogene is frequently involved in neoplastic
      transformation of different cellular histotypes. In this study, we tested the
      ability of antisense oligodeoxyribonucleotides (AS-ODN) that have mixed
      phosphodiester/phosphorothioate backbone, targeted against human N-Ras, to
      inhibit N-ras gene expression and to specifically interfere with the Ras
      dependent activity of mitogen-activated protein kinase (MAPK) in two human cell
      lines carrying an endogenous N-ras mutated allele at codon 61. Three AS-ODN that
      inhibit basal MAPK activity have been identified. Moreover, AS-ODN treatment
      resulted in potent antiproliferative effects in cell culture and great inhibition
      of N-ras mRNA levels in one of two cell lines. These studies suggest that
      antisense molecules, targeted against N-Ras, could be of considerable value as a
      tool to study the N-Ras-specific transduction pathway.

PMID- 11838637
TI  - Suppression of gene expression by RNA interference in cultured plant cells.
AB  - Suppression by double-stranded RNA (dsRNA) of the expression of a target gene is
      known as RNA interference (RNAi). No quantitative analysis of the effects of RNAi
      on the expression of specific genes in cultured plant cells has been reported.
      However, as it is possible to produce populations of cultured plant cells that
      are uniform and divide synchronously for functional analysis of genes of
      interest, we performed a quantitative study of the effects of RNAi in such cells.
      We constructed dsRNA expression plasmids for a luciferase gene under the control
      of the cauliflower mosaic virus (CaMV) 35S promoter by simply connecting sense
      and antisense sequences in a head-to-head manner. An RNAi effect was observed 24
      hours after the introduction of dsRNA expression plasmids into tobacco BY-2 cells
      by electroporation. The simple system for suppression of specific genes in plant
      cells should be useful in attempts to elucidate the roles of individual genes in
      plant cells.

PMID- 11838638
TI  - Synthesis of oligonucleotide inhibitors of DNA (Cytosine-C5) methyltransferase
      containing 5-azacytosine residues at specific sites.
AB  - The incorporation of 5-azacytosine residues into DNA causes potent inhibition of
      DNA (Cytosine-C5) methyltransferases. The synthesis of oligodeoxyribonucleotides
      incorporating single or multiple 5-aza-2'-deoxycytidine residues at precise sites
      was undertaken to generate an array of sequences containing the reactive 5
      azacytosine base as specific target sites for enzymatic methylation. Preparation
      of these modified oligonucleotides requires the use of 2-(p
      nitrophenyl)ethyloxycarbonyl (NPEOC) groups for the protection of exocyclic amino
      functions. These groups are removed under mild conditions, thus avoiding
      conventional protocols that are detrimental to the integrity of the 5-azacytosine
      ring.

PMID- 11838639
TI  - A method to select chemically modified aptamers directly.
AB  - In vitro selection is a strategy to identify high-affinity ligands of a
      predetermined target among a large pool of randomized oligonucleotides. Most in
      vitro selections are performed with unmodified RNA or DNA sequences, leading to
      ligands of high affinity and specificity (aptamers) but of very short lifetime in
      the ex vivo and in vivo context. Only a very limited number of modified
      triphosphate nucleotides conferring nuclease resistance to the oligomer can be
      incorporated by polymerases. This encourages the development of alternative
      methods for the identification of nuclease-resistant aptamers. In this paper, we
      describe such a method. After selection of 2'O-methyl oligonucleotides against
      the TAR RNA structure of HIV-1, the complementary DNA sequences are fished out of
      a pool of randomized oligodeoxynucleotides by Watson-Crick hybridization. The DNA
      fished sequences are amplified by PCR as double and single strands, the latter
      being used to fish back the chemically modified candidates from the initial
      library. This procedure allows an indirect amplification of the selected
      candidates. This enriched pool of modified sequences is then used for the next
      selection round against the target.

PMID- 11838640
TI  - Antisense oligonucleotides modulate high glucose-induced laminin overexpression
      and cell proliferation: a potential for therapeutic application in diabetic
      microangiopathy.
AB  - Vascular basement membrane (BM) thickening is a prominent and characteristic
      lesion of diabetic microangiopathy. Studies suggest that increased synthesis of
      laminin, a BM component, is associated with the development of thickened BM in
      diabetic vessels. In this study, we evaluated whether an interventive strategy
      using laminin antisense phosphorothioate oligonucleotides (Lam AS-oligos) could
      specifically inhibit high-glucose-induced laminin gene overexpression in vascular
      endothelial cells and normalize cell proliferation. Rat endothelial cells grown
      in high-glucose (30 mM) medium for 7 days showed increased laminin mRNA and
      protein level (195% +/- 28% of control, p < 0.05; 143% +/- 26% of control, p <
      0.05, respectively) and reduced cell number (79% +/- 6% of control, p < 0.05)
      compared with cells grown in normal (5 mM) glucose medium. When cells grown in
      high-glucose medium were transfected with 0.4 microM Lam AS-oligos for 48 hours
      in the presence of 8 microM lipofectin, the laminin mRNA and protein level
      decreased (121% +/- 19% and 99% +/- 15% of control, respectively), and the cell
      number was restored to near normal level (93% +/- 7% of control). The results
      indicate that the antisense strategy is effective in selectively reducing laminin
      overexpression and improving endothelial cell proliferation under high-glucose
      conditions. Thus, the As-oligos may be potentially useful for preventing the
      development of thickened vascular BM in diabetic microangiopathy.

PMID- 11838641
TI  - Alpha-anomeric configuration of GT oligodeoxynucleotide leads to loss of the
      specific aptameric and cytotoxic properties retained by the beta-anomeric analog.
AB  - The development of antisense, antigene, or aptameric oligonucleotides to modulate
      in vivo cellular functions depends on using stable biologic molecules. Previous
      investigations showed that GT oligonucleotides could exert a specific, dose
      dependent cytotoxic effect on human cancer cell lines. This is tightly related to
      the ability of these oligomers to specifically bind nuclear proteins, giving a
      complex of apparent molecular weight of 45 kDa. We demonstrated that with respect
      to the cytotoxic GT-beta-oligomer, alpha-anomeric GT analog did not alter the
      growth of the T lymphoblastic CCRF-CEM cell line, although the cells took it up
      efficiently. In agreement with this, GT-alpha-oligomer did not form the
      cytotoxicity-related 45-kDa complex with nuclear proteins. These findings likely
      could be related to the ability of GT-alpha to structure under nondenaturing
      conditions because of the high number of T in the sequence.

PMID- 11838642
TI  - Walter Haworth--synthesis of vitamin C.

PMID- 11838643
TI  - The public health problem of increasing prevalence rates of obesity and what
      should be done about it.

PMID- 11838644
TI  - Self-reported weight, weight goals, and weight control strategies of a midwestern
      population.
AB  - OBJECTIVE: To elicit from individuals in a population their current weight and
      height, weight goals, and weight control strategies to aid in design of effective
      interventions to prevent and treat obesity. SUBJECTS AND METHODS: By random digit
      dial telephone survey, 1224 adult residents of Olmsted County, Minnesota, were
      contacted between February 28 and May 5, 2000. They self-reported weights and
      weight goals and described physical characteristics associated with their desire
      to lose weight. RESULTS: Among the 1224 respondents, 65.6% of men and 47.9% of
      women reported that they were overweight (body mass index [BMI], 25.0-29.9 kg/m2)
      or obese (BMI, > or =30.0 kg/m2). Only 0.4% of men and 3.7% of women reported
      that they were underweight (BMI, <18.5 kg/m2). Of the respondents 72.6% of men
      and 85.1% of women reported that they were either trying to lose or not gain
      weight. The average weight loss goal for individuals trying to lose weight was
      23.4 pounds for men and 28.0 pounds for women. Only one third of individuals
      trying to lose weight and one fifth of individuals trying not to gain weight
      reported using the recommended approach of combining energy restriction with at
      least 150 minutes of exercise per week. CONCLUSIONS: The prevalence of overweight
      and obesity in the population and the underutilization of combining both
      restricting energy intake and exercising at least 150 minutes per week for weight
      control is high. Like the majority of people in the United States, the majority
      of people in Olmsted County desire to control their weight. The community has
      responded with plans to help residents meet their goals, although efficacy and
      outcomes remain to be determined.

PMID- 11838645
TI  - Motivation to modify lifestyle risk behaviors in women treated for breast cancer.
AB  - OBJECTIVE: To determine motivators of health behaviors (relevant to risk for
      chronic disease and cancer recurrence) after a cancer diagnosis. PATIENTS AND
      METHODS: Eighty-six women who had been treated for breast cancer (mean age, 54.8
      years; median time since diagnosis, 23.5 months) participated in this cross
      sectional study (1997-1998). Respondents completed a questionnaire assessing
      overweight or obesity status, dietary fat intake, energy expenditure,
      motivational readiness for exercise and weight loss, and variables associated
      with readiness for exercise adoption and weight loss. RESULTS: Forty-six women
      (54%) were overweight or obese, and 47 women (55%) reported dietary fat intake of
      30% or higher. Sixty-one women (72%) were in action/ maintenance stages for
      exercise adoption. A majority believed that diet and exercise can change the
      course of cancer. Overweight and obese women in the sample were more likely to be
      in early stages of motivational readiness for weight loss, and they reported
      significantly lower exercise self-efficacy and lower eating self-efficacy than
      their nonoverweight peers. However, they endorsed more benefits associated with
      weight loss than the nonoverweight subgroup. Thirty-three women (39%) reported
      both a low-fat diet and exercising at recommended levels. CONCLUSIONS: Only a
      minority of respondents reported consuming a diet low in fat and exercising at
      recommended levels, which suggests a need to improve both diet and exercise
      behaviors among women treated for breast cancer. Overweight and obese women
      reported low self-efficacy for exercise and eating, suggesting that interventions
      should focus on increasing self-efficacy for behavior change.

PMID- 11838647
TI  - Surgical pathology of carcinoid heart disease: a study of 139 valves from 75
      patients spanning 20 years.
AB  - OBJECTIVE: To quantitate the pathologic features of carcinoid plaques in a
      relatively large number of surgical specimens from a single institution. PATIENTS
      AND METHODS: Medical records, operative reports, and surgical specimens were
      reviewed from all patients with carcinoid heart disease who underwent cardiac
      valvular surgery at Mayo Clinic, Rochester, Minn, between 1980 and 2000. RESULTS:
      The study group included 75 patients (45 men, 30 women) who ranged in age from 26
      to 78 years (mean, 59 years). From these 75 patients, 139 valves had been excised
      surgically (73 tricuspid, 55 pulmonary, 6 mitral, 5 aortic). Pure regurgitation
      was the most common dysfunctional state of the tricuspid valve (80% [60/75]),
      mitral valve (97% [32/33]), and aortic valve (96% [23/24]). The pulmonary valve
      was more often both stenotic and insufficient (52% [37/71]) than purely
      regurgitant (30% [21/71]). In all cases, valve dysfunction was attributed to the
      presence of carcinoid plaques, which caused both thickening and retraction.
      Thickening was the result of both cellular proliferation and deposition of
      extracellular matrix. Proliferation of myofibroblasts was observed in all plaques
      and was mild in 49% (68/139) and moderate or severe in 51% (71/139).
      Extracellular matrix included collagen (in 99% of the 139 valves), myxoid ground
      substance (98% [136/139]), and elastin (20% [28/139]). Carcinoid plaques were
      also involved by neovascularization (94% [131/139]), chronic inflammation (94%
      [131/139]), and mast cell infiltration (64% [89/139]). Severe thickening was
      attributable primarily to collagen deposition in tricuspid valves and to
      myofibroblast proliferation and myxoid matrix in pulmonary valves. CONCLUSIONS:
      Among patients undergoing valvular surgery for carcinoid heart disease, tricuspid
      and pulmonary valves represented 92% of the excised valves (128/ 139). Although
      numerous cellular and extracellular features were common to the carcinoid
      plaques, variability in their relative expression produced appreciable
      differences in the histologic appearance among the plaques.

PMID- 11838646
TI  - Outcomes after withholding anticoagulation from patients with suspected acute
      pulmonary embolism and negative computed tomographic findings: a cohort study.
AB  - OBJECTIVE: To determine the outcome of withholding anticoagulation from patients
      with suspected acute pulmonary embolism in whom computed tomographic (CT)
      findings are interpreted as negative for pulmonary embolism. PATIENTS AND
      METHODS: This retrospective cohort study included 1512 consecutive patients
      referred from August 7, 1997, to November 30, 1998, for CT because of clinically
      suspected acute pulmonary embolism. All patients were examined by electron beam
      CT, and scanning was performed in a cephalocaudad direction from the top of the
      aortic arch to the base of the heart with 3-mm collimation, 2-mm table
      incrementation, and an exposure time of 0.2 second (130 peak kV, 620 mA, and
      standard reconstruction algorithm). Contrast material was infused at a rate of 3
      to 4 mL/s through an antecubital vein with an automated injector. Findings on CT
      were interpreted as either positive or negative. The main outcome measures were
      deep venous thrombosis, pulmonary embolism, and vital status within 3 months
      after the CT scan and the cause of death based on medical record review, mailed
      patient questionnaires, and telephone interviews. RESULTS: In 1010 patients (67%)
      CT scans were interpreted as negative for acute pulmonary embolism. Seventeen
      patients were excluded because they received anticoagulation. Of the remaining
      993 patients, deep venous thrombosis or pulmonary embolism developed in 8; 118
      patients died, 3 of pulmonary embolism. Nineteen patients were known to be alive,
      but additional clinical information could not be obtained. The 3-month cumulative
      incidence of overall deep venous thrombosis or pulmonary embolism was 0.5% (95%
      confidence interval, 0.1%-1.0%) and of fatal pulmonary embolism, 0.3% (95%
      confidence interval, 0.0%-0.7%). CONCLUSIONS: The incidence of (1) overall deep
      venous thrombosis or pulmonary embolism or (2) fatal pulmonary embolism among
      patients with suspected acute pulmonary embolism, negative CT results, and no
      other evidence of venous thromboembolism is low. Withholding anticoagulation in
      these patients appears to be safe.

PMID- 11838648
TI  - HER2 testing in patients with breast cancer: poor correlation between weak
      positivity by immunohistochemistry and gene amplification by fluorescence in situ
      hybridization.
AB  - OBJECTIVE: To evaluate amplification of the HER-2/neu gene by fluorescence ir
      situ hybridization (FISH) in tumors with weakly positive (2+) immunohistochemical
      staining. METHODS: A total of 1556 breast tumor biopsy specimens were referred to
      Mayo Medical Laboratories, Rochester, Minn, for HER2 testing between August and
      December 2000. Immunohistochemical (IHC) analysis was performed with use of a
      diagnostic test for the assessment of HER2 overexpression, the HercepTest. The
      IHC-stained slides were interpreted and scored on a scale ranging from 0 to 3+
      according to Food and Drug Administration-approved guidelines. All specimens
      scored as 2+ were also routinely evaluated by FISH with use of a HER-2/neu DNA
      probe kit (PathVysion). Specimens were determined to be amplified if the ratio of
      HER-2/neu signals to chromosome 17 centromere (CEP17) signals was higher than
      2.0. RESULTS: Thirty-eight percent of the specimens evaluated with the HercepTest
      were scored 0, 35% were 1+, 14% were 2+, and 13% were 3+. Of the 216 tumor
      specimens scored as 2+, 26 (12%) had a high level of HER-2/neu gene
      amplification, 54 (25%) demonstrated duplication of HER2, 4 (2%) deleted HER
      2/neu and/or CEP17, and 123 (57%) had no apparent HER-2/neu anomaly, no apparent
      CEP17 anomaly, nor apparent single gain (aneusomy) of CEP17. CONCLUSION: We
      recommend that all specimens with a 2+ HercepTest result be evaluated by FISH for
      HER-2/neu gene amplification. The results of both assays should be considered
      before making a decision to recommend anti-HER2 therapy.

PMID- 11838649
TI  - Cost-minimization analysis of alternative diagnostic approaches in a modeled
      patient with non-small cell lung cancer and subcarinal lymphadenopathy.
AB  - OBJECTIVE: To evaluate the costs of alternative diagnostic evaluations of
      enlarged subcarinal lymph nodes (SLNs) in modeled patients with non-small cell
      lung cancer (NSCLC). METHODS: A cost-minimization model was used to compare 5
      diagnostic approaches in the evaluation of enlarged SLNs in modeled patients with
      NSCLC. Values for the test performance characteristics and prevalence of
      malignancy in patients with SLN were obtained from the medical literature. The
      target population was adult patients known or suspected to have NSCLC with SLNs
      with a short axis length of at least 10 mm on thoracic computed tomography (CT).
      RESULTS: The lowest-cost diagnostic work-up was by initial evaluation with
      endoscopic ultrasonography-guided fine-needle aspiration (EUS FNA) biopsy
      ($11,490 per patient) compared with mediastinoscopy (with biopsy) ($13,658),
      transbronchial FNA biopsy ($11,963), CT-guided FNA biopsy ($13,027), and positron
      emission tomography ($12,887). The results were sensitive to rate of SLN
      metastases and EUS FNA sensitivity. The EUS FNA biopsy remained least costly if
      the probability of SLN metastases exceeded 24% or EUS FNA sensitivity was higher
      than 76%. Primary mediastinoscopy was the most economical if not. CONCLUSIONS:
      Which testing strategy is least costly for SLN evaluation in a modeled patient
      with NSCLC may be determined by the pretest probability of nodal metastases. Use
      of EUS FNA biopsy minimizes the cost of diagnostic evaluation in most cases.

PMID- 11838651
TI  - Complex regional pain syndrome.
AB  - Complex regional pain syndrome (CRPS), formerly known as reflex sympathetic
      dystrophy, is a regional, posttraumatic, neuropathic pain problem that most often
      affects 1 or more limbs. Like most medical conditions, early diagnosis and
      treatment increase the likelihood of a successful outcome. Accordingly, patients
      with clinical signs and symptoms of CRPS after an injury should be referred
      immediately to a physician with expertise in evaluating and treating this
      condition. Physical therapy is the cornerstone and first-line treatment for CRPS.
      Mild cases respond to physical therapy and physical modalities. Mild to moderate
      cases may require adjuvant analgesics, such as anticonvulsants and/or
      antidepressants. An opioid should be added to the treatment regimen if these
      medications do not provide sufficient analgesia to allow the patient to
      participate in physical therapy. Patients with moderate to severe pain and/or
      sympathetic dysfunction require regional anesthetic blockade to participate in
      physical therapy. A small percentage of patients develop refractory, chronic pain
      and require long-term multidisciplinary treatment, including physical therapy,
      psychological support, and pain-relieving measures. Pain-relieving measures
      include medications, sympathetic/somatic blockade, spinal cord stimulation, and
      spinal analgesia.

PMID- 11838650
TI  - An obligation for primary care physicians to prescribe physical activity to
      sedentary patients to reduce the risk of chronic health conditions.
AB  - Physical inactivity increases the risk of many chronic disorders. Numerous
      studies have convincingly demonstrated that undertaking and maintaining moderate
      levels of physical activity (eg, brisk walking 3 hours a week) greatly reduces
      the incidence of developing many chronic health conditions, most notably type 2
      diabetes mellitus, obesity, cardiovascular disease, and many types of cancers.
      However, the underlying mechanistic details of how physical activity confers such
      protective effects are not well understood and consequently constitute an active
      area of research. Although changing an individual's ingrained behavior is
      commonly perceived to be difficult, encouraging evidence suggests that intensive
      and repeated counseling by health care professionals can cause patients to become
      more physically active. Therefore, counseling patients to undertake physical
      activity to prevent chronic health conditions becomes a primary prevention
      modality. This article summarizes the vast epidemiologic and biochemical evidence
      supporting the many beneficial health implications of undertaking moderate
      physical activity and provides a rationale for incorporating physical activity
      counseling as part of routine practice in the primary care setting.

PMID- 11838653
TI  - Images and reflections from Mayo Clinic heritage.

PMID- 11838652
TI  - Acquired von Willebrand disease.
AB  - Acquired von Willebrand disease (AvWD) is a relatively rare acquired bleeding
      disorder that usually occurs in elderly patients, in whom its recognition may be
      delayed. Patients usually present predominantly with mucocutaneous bleeding, with
      no previous history of bleeding abnormalities and no clinically meaningful family
      history. Various underlying diseases have been associated with AvWD, most
      commonly hematoproliferative disorders, including monoclonal gammopathies,
      lymphoproliferative disorders, and myeloproliferative disorders. The pathogenesis
      of AvWD remains incompletely understood but includes autoantibodies directed
      against the von Willebrand factor (vWF), leading to a more rapid clearance from
      the circulation or interference with its function, adsorption of vWF by tumor
      cells, and nonimmunologic mechanisms of destruction. Laboratory evaluation
      usually reveals a pattern of prolonged bleeding time and decreased levels of vWF
      antigen, ristocetin cofactor activity, and factor VIII coagulant activity
      consistent with a diagnosis of vWD. Acquired vWD is distinguished from the
      congenital form by age at presentation, absence of a personal and family history
      of bleeding disorders, and, often, presence of a hematoproliferative or
      autoimmune disorder. The severity of the bleeding varies considerably among
      patients. Therapeutic options include desmopressin and certain factor VIII
      concentrates that also contain vWF. Successful treatment of the associated
      illness can reverse the clinical and laboratory manifestations. Intravenous
      immunoglobulins have also shown some efficacy in the management of AvWD,
      especially cases associated with monoclonal gammopathies. Awareness of AvWD is
      essential for diagnosis and appropriate management.

PMID- 11838654
TI  - 58-year-old man with fatigue and flank pain.

PMID- 11838655
TI  - Reversible restrictive cardiomyopathy due to light-chain deposition disease.
AB  - Systemic light-chain deposition due to plasma cell dyscrasias manifests as a form
      of restrictive cardiomyopathy with diastolic ventricular dysfunction. Although
      these manifestations are likely to be cardiac amyloidosis, whether these
      pathological conditions are reversible after treatment of the underlying plasma
      cell disorders is unknown. To our knowledge, we describe the first patient with
      cardiac light-chain deposition due to multiple myeloma in whom echocardiographic
      and biochemical factors of cardiac function were ameliorated dramatically after
      remission of this disorder. We emphasize that restrictive cardiomyopathy due to
      light-chain deposition may be reversible and have a relatively better prognosis
      after remission of plasma cell dyscrasias.

PMID- 11838656
TI  - Extracorporeal photopheresis and adjuvant aerosolized granulocyte-macrophage
      colony-stimulating factor for Sezary syndrome.
AB  - Encouraged by preliminary phase 1 studies of aerosolized granulocyte-macrophage
      colony-stimulating factor (GM-CSF, sargramostim) in the treatment of patients
      with melanoma and other malignancies, we treated a 72-year-old patient with
      Sezary syndrome, using alternate-week cycles of aerosolized GM-CSF in combination
      with monthly cycles of extracorporeal photopheresis (ECP). Sezary syndrome, one
      of the more aggressive forms of cutaneous T-cell lymphoma, is a devastating and
      highly symptomatic form of non-Hodgkin lymphoma in which malignant clones of
      mature helper CD4 T cells, containing large, convoluted nuclei known as Sezary
      cells, circulate in the blood and infiltrate skin. Extracorporeal photopheresis,
      an immunomodulatory therapy, has become a primary treatment for patients with
      Sezary syndrome. This pheresis-based therapy combines psoralen and ultraviolet A
      radiation as systemic photochemotherapy to induce immune responses. However, the
      activity and efficacy of ECP vary considerably. To our knowledge this is the
      first patient with Sezary syndrome treated with adjuvant aerosolized GM-CSF
      combined with ECP. It produced clinical improvement and decreased the number of
      circulating Sezary cells in a previously ECP-refractory patient.

PMID- 11838657
TI  - Sumatriptan use in patients with migraine.

PMID- 11838658
TI  - Thyroid function studies in patients with unintentional weight loss.

PMID- 11838659
TI  - The aldosterone-renin ratio and primary aldosteronism.

PMID- 11838660
TI  - The shortage of anesthesiologists--and other medical specialists.

PMID- 11838661
TI  - Vibro-acoustic tissue mammography.
AB  - A novel method for detection and imaging of microcalcifications in breast tissue
      is presented. The method, called vibro-acoustography, uses the radiation force of
      ultrasound to vibrate tissue at low (kHz) frequency and utilizes the resulting
      response to produce images that are related to the hardness of the tissue. The
      method is tested on human breast tissues. The resulting vibro-acoustographic
      images are in agreement with corresponding X-ray mammography images of the
      specimens. The existence of microcalcifications in locations indicated by vibro
      acoustography is confirmed by histology. Microcalcifications as small as 110
      microm in diameter are detected by this method. Resulting vibro-acoustographic
      images show microcalcifications with high contrast with respect to the background
      soft tissue. Structures such as dense sclerotic tissue do not seem to interfere
      with detection of microcalcifications.

PMID- 11838662
TI  - Parameter space warping: shape-based correspondence between morphologically
      different objects.
AB  - This paper presents a novel and comprehensive method for the automated
      determination of correspondences between two morphologically different two
      dimensional (2-D) or three-dimensional (3-D) objects. Correspondences are
      determined by warping parametric representations of the objects to be matched.
      The warp is guided by the minimization of a similarity criterion function that
      measures features related to structural correspondence, including Euclidian point
      to-point distance and differences in normals and curvature. The method uses a
      continuous harmonic parameterization for both the object and the warp, which
      provides: 1) a high degree of computational efficiency; 2) robust extraction of
      differential features, not subject to discretization errors or noise
      amplification in differentiation; 3) direct formulation of constraints to avoid
      overlaps in the resulting correspondence set; and 4) a scale-space paradigm of
      object shape and warp. The new method does not search for individual landmarks,
      but operates with a complete, integrated representation of the object geometry.
      The method was tested on 2-D and 3-D objects with substantial shape differences.
      Results demonstrated substantial improvements of 2%-33% in correspondence
      accuracy and 15%-59% in correspondence quality compared with direct registration
      methods.

PMID- 11838663
TI  - Segmentation of ultrasound B-mode images with intensity inhomogeneity correction.
AB  - Displayed ultrasound (US) B-mode images often exhibit tissue intensity
      inhomogeneities dominated by nonuniform beam attenuation within the body. This is
      a major problem for intensity-based, automatic segmentation of video-intensity
      images because conventional threshold-based or intensity-statistic-based
      approaches do not work well in the presence of such image distortions. Time gain
      compensation (TGC) is typically used in standard US machines in an attempt to
      overcome this. However this compensation method is position-dependent which means
      that different tissues in the same TGC time-range (or corresponding depth range)
      will be, incorrectly, compensated by the same amount. Compensation should really
      be tissue-type dependent but automating this step is difficult. The main
      contribution of this paper is to develop a method for simultaneous estimation of
      video-intensity inhomogeities and segmentation of US image tissue regions. The
      method uses a combination of the maximum a posteriori (MAP) and Markov random
      field (MRF) methods to estimate the US image distortion field assuming it follows
      a multiplicative model while at the same time labeling image regions based on the
      corrected intensity statistics. The MAP step is used to estimate the intensity
      model parameters while the MRF step provides a novel way of incorporating the
      distributions of image tissue classes as a spatial smoothness constraint. We
      explain how this multiplicative model can be related to the ultrasonic physics of
      image formation to justify our approach. Experiments are presented on synthetic
      images and a gelatin phantom to evaluate quantitatively the accuracy of the
      method. We also discuss qualitatively the application of the method to clinical
      breast and cardiac US images. Limitations of the method and potential clinical
      applications are outlined in the conclusion.

PMID- 11838664
TI  - Mutual information-based rigid and nonrigid registration of ultrasound volumes.
AB  - We investigated the registration of ultrasound volumes based on the mutual
      information measure, a technique originally applied to multimodality registration
      of brain images. A prerequisite for successful registration is a smooth, quasi
      convex mutual information surface with an unambiguous maximum. We discuss the
      necessary preprocessing to create such a surface for ultrasound volumes.
      Abdominal and thoracic organs imaged with ultrasound typically move relative to
      the exterior of the body and are deformable. Consequently, four specific
      instances of image registration involving progressively generalized
      transformations were studied: rigid-body, rigid-body + uniform scaling, rigid
      body + nonuniform scaling, and affine. Registration was applied to clinically
      acquired volumetric images. The accuracy was comparable with the voxel dimension
      for all transformation modes, although it degraded as the transformation grew
      more complex. Likewise, the capture range became narrower with the complexity of
      transformation. As the use of real-time three-dimensional ultrasound becomes more
      prevalent, the method we present should work well for a variety of applications
      examining serial anatomic and physiologic changes. Developers of these clinical
      applications would match the deformation model of their problem to one of the
      four transformation models presented here.

PMID- 11838665
TI  - MALDI-TOF-MS analysis of droplets prepared in an electrodynamic balance: "wall
      less" sample preparation.
AB  - Methodology enabling mass spectral analysis of the composition of droplet(s)
      prepared in an electrodynamic balance (EDB) by matrix-assisted laser
      desorption/ionization (MALDI) is described. The dc field surrounding the
      electrodynamic balance was manipulated to eject single droplets at a time from
      the EDB thereby causing their deposition onto a MALDI sample plate precoated with
      matrix. When the laser was directed onto the droplet(s) and held stationary,
      marked gains in the signal-to-noise and signal-to-background ratios were realized
      with each subsequent mass spectrum due to the suppression of matrix cluster ion
      formation. Optical microscopy of the plate, after 1024 laser shots were fired at
      eight droplets that had been deposited one on top of the other, revealed a
      residual island of droplet matter (area approximately 3.1 x 10(-9) m2) inside the
      region where the crystalline matrix had been ablated away within the laser spot
      (area approximately 1.6 x 10(-8) m2). Removing the predried crystalline matrix
      layer and, instead, adding matrix into the starting solution was found to be a
      more effective means of suppressing matrix cluster ion formation. The chemical
      composition of the droplet(s) prepared in the EDB is discussed with regard to
      sample preconcentration, the images of the laser spot after MALDI, matrix cluster
      ion suppression, and the possibility for improved quantitation and detection
      limits by MALDI-TOF-MS.

PMID- 11838666
TI  - Single-neuron analysis using CE combined with MALDI MS and radionuclide
      detection.
AB  - Capillary electrophoresis (CE) has been combined with matrix-assisted laser
      desorption/ionization mass spectrometry (MALDI MS) and radionuclide detection to
      assay mass-limited biological samples. Nanovial sampling techniques enable
      injections into the CE capillary from 50 to 150-nL volume samples; after the
      separation, nanoliter fraction collection combines the CE effluent with a MALDI
      matrix and minimizes sample spreading, thus allowing both MALDI MS and
      radionuclide detection on the CE fractions. MALDI MS complements the elution time
      information of CE by providing accurate molecular mass data, and radionuclide
      detection provides zeptomole limits of detection with quantitative information.
      While MALDI MS detects all fully processed peptides at sufficient concentration,
      culturing the neuron in media containing 35S-Met provides selective radionuclide
      detection of newly synthesized methionine-containing peptides. The analysis and
      detection of the expected neuropeptides and hormones in a single 40-microm bag
      cell neuron from Aplysia californica with CE/MALDI MS/radionuclide detection
      demonstrates the ability of this hyphenated approach to work with chemically
      complex mass-limited samples.

PMID- 11838667
TI  - A colorimetric gold nanoparticle sensor to interrogate biomolecular interactions
      in real time on a surface.
AB  - This paper presents a new label-free optical method to study biomolecular
      interactions in real time at the surface of an optically transparent substrate.
      The method relies on the change in the absorbance spectrum of a self-assembled
      monolayer of colloidal gold on glass, as a function of biomolecular binding to
      the surface of the immobilized colloids. Using this approach, we demonstrate
      proof of principle of a label-free optical biosensor to quantify biomolecular
      interactions in real time on a surface in a commercially available UV-visible
      spectrophotometer and of a colorimetric end-point assay using an optical scanner.
      The spectrophotometric sensor shows concentration-dependent binding and a
      detection limit of 16 nM for streptavidin. The sensor is easy to fabricate, is
      reproducible in its performance, has minimal technological requirements, namely,
      the availability of an UV-visible spectrophotometer or an optical scanner, and
      will enable high-throughput screening of biomolecular interactions in real time
      in an array-based format.

PMID- 11838668
TI  - Potentiometric estimation of the stability constants of ion-lonophore complexes
      in ion-selective membranes by the sandwich membrane method: theory, advantages,
      and limitations.
AB  - Segmented sandwich membrane method of studying stoichiometry and stability
      constants of ion-ionophore complexes in ion-selective membranes is considered in
      detail. The experimental data (reported earlier in Russian) concerning complexes
      of various ions with valinomycin, with H+-selective neutral ionophore
      hexabutyltriamidophosphate, and with anion-binding neutral ionophore p-hexyl
      trifluoroacetylbenzoate is presented in a compact form. Advantages of titration
      technique in the sandwich membrane method (the presence of an internal criterion
      of reliability, and the possibility of direct determination of complex
      stoichiometry coefficients) are specially addressed. Biases of the estimates of
      the constants caused by ion-pair formation in real membranes and by diffusion
      potential are analyzed by means of computer simulations. The possibility of
      revealing two coexisting complexes with different compositions is also discussed.

PMID- 11838669
TI  - Selectivity of lithium electrodes: correlation with ion-lonophore complex
      stability constants and with interfacial exchange current densities.
AB  - Lithium-selective electrodes with solvent polymeric membranes based on two
      different dicyclohexylamide neutral ionophores are studied systematically. The
      selectivity of lithium response is studied by means of the ordinary
      potentiometric experiments. Stability constants of lithium, sodium, and potassium
      ions with the neutral ionophores are measured by means of the segmented sandwich
      membrane method. Charge transfer through the membrane bulk and across the
      membrane/solution interface is studied by means of electrochemical impedance
      spectroscopy. Well-resolved Faradaic impedance semicircles are obtained, allowing
      calculation of exchange current densities for lithium, sodium, and potassium. It
      is clearly demonstrated that the potentiometric selectivity coefficients
      correlate well with thermodynamic equilibrium parameters. The correlation with
      exchange current densities also exists, although it is low, and seems rather
      qualitative than quantitative. The results are treated in favor of equilibrium at
      the membrane/solution interface. It is also concluded (tentatively) that the
      kinetic description is equivalent to the equilibrium one, giving evidence that
      ion-ionophore complexes form directly at the interface.

PMID- 11838670
TI  - Electrogenerated chemiluminescence detection in reversed-phase liquid
      chromatography.
AB  - Electrogenerated chemiluminescence (ECL) has been developed as a detection method
      for liquid chromatography. The radical cation of tri-p-tolylamine (TPTA) is used
      as a common electron acceptor for the electrogenerated radical anions of a
      variety of organic analytes. ECL is accomplished with a high-frequency potential
      pulse program applied to a microelectrode immersed in the column eluent. ECL
      detection is demonstrated with reversed-phase liquid chromatography. Selectivity
      at the ECL detector is shown to be tunable based on differing electrochemical
      conditions and excited-state energetics. Low minimum detection limits in ECL are
      attributed to the dependence on the photon detector shot noise, allowing a limit
      of detection of 0.14 nM for perylene in the presence of 0.1 mM TPTA. A
      derivatization agent useful for ECL detection is demonstrated by the use of
      naphthalene-2,3-dicarboxaldehyde. This reagent, which does not itself result in
      ECL, forms ECL candidates following reaction with primary amines.

PMID- 11838671
TI  - Electrochemical evaluation of the interaction between endocrine disrupter
      chemicals and estrogen receptor using 17,beta-estradiol labeled with daunomycin.
AB  - A new electrochemical screening method for endocrine disrupting chemicals (EDCs)
      was developed. To evaluate the binding capacity of EDCs to the estrogen receptor
      (ER), 17beta-estradiol labeled with daunomycin as an electroactive compound was
      prepared. The electrochemical sensitivity of the prepared labeled estradiol (LE)
      was high, as compared with daunomycin. The interaction between LE and ER was
      observed by the decrease in the electrode response of LE, indicating the specific
      binding of LE with ER. The competitive reaction between LE and 17beta-estradiol
      for the limiting binding site on ER produced increases in the peak current of LE.
      The relative standard deviation at 1 x 10(-8) M 17beta-estradiol was about 10.0%
      (n = 7). The binding affinity between EDC and ER was also evaluated by comparison
      with 17beta-estradiol-ER interaction. Bisphenol A, p-nonylphenol and p,p'-DDT was
      used as a test compound. All test compounds demonstrated some ability to bind
      with ER. This electrochemical binding assay illustrates a new method for
      evaluating the binding capacity of EDCs to ER without the need for a separation
      procedure for the bound and free LE.

PMID- 11838673
TI  - The strength of multiple choices for chemical research.

PMID- 11838674
TI  - Electrochemiluminescent detection of metal cations using a ruthenium(II)
      bipyridyl complex containing a crown ether moiety.
AB  - The effects of metal ions on the electrochemiluminescence (ECL) properties of
      (bpy)2Ru(AZA-bpy) (bpy = 2,2'-bipyridine; AZA-bpy = 4-(N-aza-18-crown-6-methyl
      2,2'-bipyridine) have been investigated. The electrochemistry, photophysics and
      ECL of Ru(bpy)3(2+) in the presence of Pb2+, Hg2+, Cu2+, and K+ are reported. The
      anodic oxidation of Ru(bpy)3(2+) produces ECL in the presence of tri-n
      propylamine (TPrA) in 50:50 (v/v) CH3CN:H2O solution. Increases in ECL efficiency
      (photons generated per redox event) up to 20-fold that depend on both the
      concentration and nature of the metal ion have been observed, making this an
      interesting system for electrochemiluminescence metal ion sensing.

PMID- 11838675
TI  - Electrogenerated chemiluminescence. 68. Detection of sodium ion with a
      ruthenium(II) complex with crown ether moiety at the 3,3'-positions on the 2,2'
      bipyridine ligand.
AB  - We show here how a Ru(bpy)2(CE-bpy) complex can be used for the ECL detection of
      sodium ion in both aqueous and nonaqueous media. Recognition of Na+ by the crown
      ether moiety in CE-bpy results in a significant increase in the ECL emission
      intensity of the complex.

PMID- 11838672
TI  - Response times of carbon fiber microelectrodes to dynamic changes in
      catecholamine concentration.
AB  - The electrode response time and the measured concentrations during dynamic
      catecholamine changes were compared using constant potential amperometry and fast
      scan cyclic voltammetry. The amperometric response to a rectangular pulse of
      catecholamine is more rectangular than the cyclic voltammetric response; however,
      the response times are very similar when, during cyclic voltammetry, the temporal
      lag due to adsorption and desorption of catecholamine to the electrode is removed
      by deconvolution. Deconvolution of cyclic voltammetry data was applied to
      stimulated dopamine release in vivo, allowing for modeling of release and uptake
      kinetics and to measure catecholamine release from single cells, resulting in
      better resolution of peaks from single vesicles. In vitro postcalibrations were
      performed to calculate concentrations of catecholamine measured with cyclic
      voltammetry and amperometry. The addition of 600 microM ascorbic acid to the
      postcalibration buffer, allowing a catalytic reaction to regenerate dopamine,
      resulted in similar calculated concentrations for stimulated release of dopamine
      using amperometry and cyclic voltammetry. Using deconvoluted cyclic voltammetry
      to remove the response time lag and adding ascorbic acid to the calibration
      buffer, the shape and concentration of dynamic catecholamine changes are very
      similar when measured with constant potential amperometry and cyclic voltammetry.

PMID- 11838676
TI  - Influence of roughness on the admittance of the quartz crystal microbalance
      immersed in liquids.
AB  - The effect of surface roughness on the response of the QCM has been considered,
      both theoretically and experimentally. A new theoretical approach to the
      description of the effect of roughness on the response of the QCM is proposed
      that accounts for the multiscale nature of roughness. Performing experiments in
      liquids having a wide range of viscosity and density made it possible to
      understand, for the first time, what characteristics of roughness influence the
      QCM experiments. The most important conclusion of the current study is that, to
      understand the experimental data, one has to take into account at least two types
      of roughness: slight and strong. We found that measurements of the frequency
      shift observed are not sufficient for the interpretations of the experimental
      data observed, and a full analysis of the impedance spectrum is called for.

PMID- 11838677
TI  - 2,4,6-triphenylpyrylium ion encapsulated into zeolite Y as a selective electrode
      for the electrochemical determination of dopamine in the presence of ascorbic
      acid.
AB  - 2,4,6-Triphenylpyrylium ion immobilized inside the supercages of zeolite Y
      enhances by 1-2 orders of magnitude the response of electrochemical oxidation of
      dopamine in neutral aqueous media accompanied by a remarkable inhibition of post
      electron-transfer reactions. The negative charge of the zeolite framework in
      which the 2,4,6-triphenylpyrylium ion is incorporated blocks the electrochemical
      oxidation of the negative ascorbate ion, enabling the determination of micromolar
      concentrations of dopamine in the presence of a large excess (10(3)-10(4) times)
      of ascorbate in phosphate buffer (pH 7.4). Under optimized conditions, linear
      calibration plots were obtained for a differential pulse detection mode over the
      range 250-1 microM dopamine with a sensitivity of 62 nA/microM and a detection
      limit (S/N = 3) of 0.2 microM in the presence of 1.0 mM ascorbate.

PMID- 11838678
TI  - Ketocyanine dyes: H+ selective lonophores for use in integrated waveguides
      absorbance optodes.
AB  - The optical and analytical characteristics of a series of neutral H+-selective
      chromoionophores in PVC membranes are described. Such indicators have been
      synthesized so that they can operate in bulk optode membranes as the chemically
      active region of integrated waveguide absorbance optodes (IWAOs), lambdamax near
      780 nm. Their spectral characteristics, acid-base properties, chemical stability,
      and solubility in the membrane phase are given and discussed. The response
      characteristics are first tested in a conventional absorbance/transmittance flow
      cell. They offer a wide range of pKa's in PVC membranes, good sensitivity as a
      result of their high molar absortivities, excellent solubility in the
      plasticizer, and quick response times. They present good chemical stability in
      common laboratory conditions when stored in the dark, and the absence of leaching
      guarantees a long lifetime. Membranes have been finally applied as the sensing
      region of an integrated waveguide optode, demonstrating the extraordinary
      sensitivity improvement while preserving the remaining analytical features.
      Calibration curve slopes are multiplied by 3-28, and response times lower than 2
      min are obtained.

PMID- 11838679
TI  - Tandem mass spectrometry of ribonuclease A and B: N-linked glycosylation site
      analysis of whole protein ions.
AB  - Recently, an approach for the "top down" sequence analysis of whole protein ions
      has been developed, employing electrospray ionization, collision-induced
      dissociation, and ion/ion proton-transfer reactions in a quadrupole ion trap mass
      spectrometer. This approach has now been extended to an analysis of the [M +
      12H]12+ to [M + 5H]5+ ions of ribonuclease A and its N-linked glycosylated
      analogue, ribonuclease B, to determine the influence of the posttranslational
      modification on protein fragmentation. In agreement with previous studies on the
      fragmentation of a range of protein ions, facile gas-phase fragmentation was
      observed to occur along the protein backbone at the C-terminal of aspartic acid
      residues, and at the N-terminal of proline, depending on the precursor ion charge
      state. Interestingly, no evidence was found for gas-phase deglycosylation of the
      N-linked sugar in ribonuclease B, presumably due to effective competition from
      the facile amide bond cleavage channels that "protect" the N-linked glycosidic
      bond from cleavage. Thus, localization of the posttranslational modification site
      may be determined by analysis of the "protein fragment ion mass fingerprint".

PMID- 11838680
TI  - A validated liquid chromatography/tandem mass spectrometry assay for cis
      amminedichloro(2-methylpyridine)platinum(II) in human plasma ultrafiltrate.
AB  - The clinical use of platinum drugs as anticancer agents has encountered problems
      when relating pharmacokinetic profiles with efficacy and toxicity is attempted.
      This has been mainly due to the lack of specific and sensitive analytical
      methodology to examine concentrations of the unbound drug in plasma. The presence
      of a carbocyclic ring on the new drug, cis-amminedichloro(2
      methylpyridine)platinum(II) (ZD0473) suggested that it would be possible to
      develop the first stable isotope dilution LC/MS assay for a platinum drug in
      human plasma ultrafiltrate samples. The dichloro form of the drug exists in
      equilibrium with at least two aquated forms in plasma. The molecular form of the
      drug, therefore, depends on the length of time that the plasma sample is
      maintained at room temperature before freezing. Therefore, we have developed a
      method that quantitatively converts the aquated species back to the dichloro form
      of the parent drug so that a single molecular species can be analyzed. Selected
      reaction monitoring was performed on the transition of m/z 393 [M + NH4]+ to m/z
      304 [M + NH4 -NH3 - 2 x HCl]- for ZD0473, and m/z 400 [M + NH4]+ to m/z 310 [M +
      NH4 - NH3 - HCl - 2HCl]+ for [2H7]ZD0473. The standard curves were fitted to a
      quadratic regression over the range from 10 to 5000 ng/mL in human plasma
      ultrafiltrate. The lower limit of quantitation for ZD0473 was 10 ng/mL for 100
      microL of plasma ultrafiltrate. This simple, rapid, reliable, and sensitive
      method of quantitation had excellent accuracy and precision. The method provided
      adequate sensitivity for the analysis of plasma ultrafiltrate samples from a
      phase II study in which ZD0473 was administered to patients as an intravenous
      infusion at a dose of 150 mg/m2.

PMID- 11838681
TI  - Electrospray ionization fourier transform ion cyclotron resonance mass
      spectrometry of dissolved organic phosphorus species in a treatment wetland after
      selective isolation and concentration.
AB  - A method for the selective concentration of dissolved organic phosphorus (DOP)
      from complex surface water samples for the first time allows mass spectral
      characterization of individual DOP compounds in phosphorus-limited ecosystems.
      The entire dissolved organic matter (DOM) pool is first separated according to
      molecular weight by tangential cross-flow ultrafiltration (CFF). DOP is
      selectively isolated and concentrated from CFF fractions by a barium
      precipitation procedure. The DOP precipitate is then reconstituted in distilled
      water and excess barium, and other cations are removed with an ion-exchange
      resin. The DOP isolation/concentration step can provide up to 15-fold
      concentration and 300-fold concentration of high molecular weight DOP when
      combined with the inherent concentration provided by CFF. The procedure also
      removes cations and most of the background DOM, leaving DOP in a matrix suitable
      for electrospray ionization and mass spectral characterization. Model organic
      phosphate standards representative of DOP species expected in aquatic
      environments were used to evaluate the technique. It was then applied to a series
      of high molecular weight (>1000) CFF retentates isolated from sites within the
      Everglades Nutrient Removal (ENR) treatment wetland. The elemental compositions
      of several individual DOP compounds observed at different sites within the ENR
      were determined by electrospray ionization Fourier transform ion cyclotron
      resonance mass spectrometry.

PMID- 11838682
TI  - Phosphoprotein isotope-coded affinity tags: application to the enrichment and
      identification of low-abundance phosphoproteins.
AB  - The use of a phosphoprotein isotope-coded affinity tag (PhIAT), which employs
      differential isotopic labeling and biotinylation, has been shown capable of
      enriching and identifying mixtures of low-abundance phosphopeptides. A denatured
      solution of beta-casein was labeled using the PhIAT method, and after proteolytic
      digestion, the labeled peptides were isolated using immobilized avidin. The
      recovered peptides were separated by capillary reversed-phase liquid
      chromatography and identified by tandem mass spectrometry. PhIAT-labeled peptides
      corresponding to known O-phosphorylated peptides from beta-casein were identified
      along with the phosphorylated peptides from alphas1-casein and alphas2-casein,
      known low-level (<5%) contaminants of commercially available beta-casein. All of
      the casein-phosphorylated residues identified by the present PhIAT approach
      correspond to previously documented sites of phosphorylation. The results
      illustrate the efficacy of the PhIAT-labeling strategy to not only enrich
      mixtures for phosphopeptides but also, more importantly, permit the detection and
      identification of low-level phosphopeptides. In addition, the differences in the
      phosphorylation state could be determined between phosphopeptides in comparative
      samples by stoichiometric conversion using the light and heavy isotopic versions
      of the PhIAT reagents. Overall, our results exemplify the application of the
      PhIAT approach and demonstrate its utility for proteome-wide phosphoprotein
      identification and quantitation.

PMID- 11838683
TI  - Nonaqueous capillary electrochromatographic separation of synthetic neutral
      polymers by size exclusion chromatography using polymeric stationary phases.
AB  - In this paper, we report the separations of large, neutral, synthetic polymers
      using primarily a nonaqueous mobile phase without the use of a supporting
      electrolyte. The size- exclusion-based mechanism for separation was achieved on
      sulfonated polystyrene/divinylbenzene stationary phases. The effect of water,
      voltage, stationary phase exchange capacity, and pore size were investigated. The
      stationary phase and solvent interactions were studied by attenuated total
      reflectance Fourier transform infrared spectroscopy (ATR FT-IR) and a possible
      mechanism for the generation of EOF in the THF/water system is provided. Linear
      calibration curves were obtained for polystyrenes ranging in MW from 5K to 2M,
      for columns made using a combination of high capacity ion exchanger and a neutral
      polystyrene/divinylbenzene material of varied pore sizes. Analysis of
      polyurethane, polystyrene, and other polymer samples using CEC correlated well
      with results obtained by conventional HPLC. The size exclusion CEC separations
      provide an alternative mode for determining the relative molecular weights of
      polymers, with reduced solvent consumption.

PMID- 11838684
TI  - Use of surface-modified capillaries in the separation and characterization of
      metallothionein isoforms by capillary electrophoresis inductively coupled plasma
      mass spectrometry.
AB  - The separation of metallothionein (ML) isoforms using capillary electrophoresis
      (CE) has been improved by applying surface-modified capillaries, and the metal
      composition of MTs has been characterized by subsequent inductively coupled
      plasma sector field mass spectrometry (ICPSFMS). Nine MT complexes in a
      commercial preparation from rabbit liver were successfully separated on an
      anionic polymer-coated column, prepared by immobilizing poly(2-acrylamido-2
      methyl-1-propanesulfonic acid) on the fused-silica surface via a linking agent.
      On uncoated capillaries or those coated dynamically with cationic materials, only
      three complexes could be separated. Online isotope dilution analysis combined
      with CE/ICPSFMS indicated the stoichiometric molar metal contents in the MT
      complexes.

PMID- 11838685
TI  - Electrokinetic stacking injection of neutral analytes under continuous
      conductivity conditions.
AB  - In capillary electrokinetic chromatography, neutral analytes can be injected by
      electroosmotic flow directly from a sample matrix into a separation buffer
      containing an electrokinetic vector with an opposite mobility. Analytes are
      injected at the velocity of electroosmotic flow but are retained at the interface
      of the sample matrix co-ion and separation buffer micelle zones as
      analyte/micelle complexes. A simple electrokinetic chromatography system
      containing sodium dodecyl sulfate as the micellar agent with borate as the
      buffering electrolyte included in the separation buffer and in the sample matrix
      to provide continuous conductivity was investigated. Concentrations of the
      micelle, methanol, and borate in the separation buffer were explored to increase
      maximum injection length of neutral analytes. Reducing the analyte velocity in
      the separation buffer without substantially decreasing the velocity of the
      analyte during injection from the sample vial allowed greatly extended sample
      plug injection lengths. It is presently possible to inject sample solvent volumes
      equivalent to approximately 7 effective capillary lengths (180 cm) with a 50
      microm-i.d. capillary (24.5 cm effective capillary length), total volume of
      sample injection approximately 3.5 microL Equations describing the injection
      process and maximum injection lengths for this mode of stacking in electrokinetic
      capillary chromatography are introduced. The result of this work leads to a
      postulated generalization of electrokinetic stacking injection maximums for
      electrophoretic processes, and the concept of orthogonal analyte
      stacking/injection systems is discussed.

PMID- 11838686
TI  - An integrated fritless column for on-chip capillary electrochromatography with
      conventional stationary phases.
AB  - A new polymer device for use with conventional particulate stationary phases for
      on-chip, fritless, capillary electrochromatography (CEC) has been realized. The
      structure includes an injector and a tapered column in which the particles of the
      stationary phase are retained and stabilized. The chips were easily fabricated in
      poly(dimethylsiloxane) using deep-reactive-ion-etched silicon masters, and tested
      using a capillary electrophoretic separation of FITC-labeled amino acids. To
      perform CEC, the separation channel was packed using a vacuum with 3-microm,
      octadecylsilanized silica microspheres. The packing was stabilized in the column
      by a thermal treatment, and its stability and quality were evaluated using in
      column indirect fluorescence detection. The effects of voltage on electro-osmotic
      flow and on efficiency were investigated, and the separation of two neutral
      compounds was achieved in less than 15 s.

PMID- 11838687
TI  - Hollow fiber-protected liquid-phase microextraction of triazine herbicides.
AB  - A new microextraction technique termed hollow fiber-protected liquid-phase
      microextraction (LPME) was developed. Triazines were employed as model compounds
      to assess the extraction procedure and were determined by gas chromatography/mass
      spectrometry. Toluene functioned as both the extraction solvent and the
      impregnation solvent. Some important extraction parameters, such as effect of
      salt, agitation, pH, and exposure time were optimized. The new method provided
      good average enrichment factors of > 150 for eight analytes, good repeatability
      (RSDs <3.50%, n = 7), and good linearity (r2 > or = 0.9995) for spiked deionized
      water samples. The limits of detection (LODs) were in the range of 0.007-0.063
      microg/L (S/N = 3) under selected ion monitoring mode. In addition to enrichment,
      hollow fiber-protected LPME also served as a technique for sample cleanup because
      of the selectivity of the membrane, which prevented large molecules and
      extraneous materials, such as humic acids in solution, from being extracted. The
      utilization of this procedure in the extraction of a slurry sample (mixture of
      soil and water) also gave good precision (RSDs <5.00%, n = 3) and LODs (0.04-0.18
      microg/L, S/N = 3). Finally, the comparison of the new method with the static
      solvent drop LPME and solid-phase microextraction was performed. The results
      demonstrated that hollow fiber-protected LPME was a fast, accurate, and stable
      sample pretreatment method that gave very good enrichment factors for the
      extraction of triazine herbicides from aqueous or slurry samples.

PMID- 11838688
TI  - A colorimetric assay for the ages.

PMID- 11838689
TI  - Prediction of soil adsorption coefficients from retention parameters on three
      reversed-phase liquid chromatographic columns.
AB  - Reversed-phase high-performance liquid chromatographic (RP-HPLC) retention
      parameters, which are determined by the intermolecular interactions in retention
      process, can be considered as the chemical molecular descriptors in linear free
      energy relationships (LFERs). On the basis of the characterization and comparison
      of octadecyl-bonded silica gel (ODS), cyano-bonded silica gel (CN), and phenyl
      bonded silica gel (Ph) columns with linear solvation energy relationships
      (LSERs), a new multiple linear regression model using RP-HPLC retention
      parameters on ODS and CN columns as variables for estimation of soil adsorption
      coefficients was developed. It was tested on a set of reference substances from
      various chemical classes. The results showed that the multicolumn method was more
      promising than a single-column methpd was for the estimation of soil adsorption
      coefficients. The accuracy of the suggested model is identical with that of
      LSERs.

PMID- 11838690
TI  - Tweaking entropy's edge.

PMID- 11838691
TI  - Unsuitability of Cr(II) reduction for the measurement of sulfides in oxic water
      samples.
AB  - After developing a highly sensitive method for detecting acid-volatile sulfides
      (AVS) in oxic freshwaters, we hoped to apply that method to measuring a different
      class of dissolved reduced sulfur compounds, chromium-labile sulfides (CLS). A
      popular method for measuring this pool of sulfides in sediments relies on
      reduction dissolution of metal sulfides by Cr(II) and has been employed by
      researchers for over 15 years. Here, we demonstrate that this method is
      inappropriate for measuring CLS in oxic freshwaters in which sulfate
      concentrations are large relative to the dissolved metal sulfides. We observe the
      reduction of sulfate by Cr(II), and this presents a significant interference.

PMID- 11838692
TI  - Coupling fiber optics to a permeation liquid membrane for heavy metal sensor
      development.
AB  - We present the first sensing system for metal ions based on the combination of
      separation/preconcentration by a permeation liquid membrane (PLM) and
      fluorescence detection with an optical fiber. As a model, a system for the
      detection of Cu(II) ions was developed. The wall of a polypropylene hollow fiber
      serves as support for the permeable liquid membrane. The lumen of the fiber
      contains the strip solution in which Cu(II) is accumulated. Calcein, a
      fluorochromic dye, acts as stripping agent and at the same time as metal
      indicator. The quenching of the calcein fluorescence upon metal accumulation in
      the strip phase is detected with a multimode optical fiber, which is incorporated
      into the lumen. Fluorescence is excited with a blue LED and detected with a
      photon counter. Taking advantage of the high selectivity and sensitivity of PLM
      preconcentration, a detection limit for Cu(II) of approximately 50 nM was
      achieved. Among five tested heavy metal ions, Pb(II) was the only major
      interfering species. The incorporation of small silica optical fibers into the
      polypropylene capillary allows for real-time monitoring of the Cu(II)
      accumulation process.

PMID- 11838693
TI  - Electrochemistry, endocrine disruptors, and the environment.

PMID- 11838694
TI  - Time-efficient method for the determination of 210Pb, 210Bi, and 210Po activities
      in seawater using liquid scintillation spectrometry.
AB  - A novel method has been developed for determining the natural decay series
      radionuclides (NDS), 210Pb, 210Bi, and 210Po, in seawater by way of state-of-the
      art liquid scintillation spectrometry. For 210Pb analysis, the method makes use
      of a 212Pb yield tracer, prepared by ion exchange separation from aged Th(NO3)4.
      210Bi recovery is determined using 207Bi as the yield tracer, and 210Po is
      determined using the conventional 208Po yield tracer. The limits of detection for
      this method are 0.32, 0.34, and 0.004 mBq 1-1 for 210Pb, 210Bi, and 210Po,
      respectively. The analysis can be completed within 10 days, as compared with up
      to one year for traditional methods. Results are presented for a preliminary
      study of 210Pb, 210Bi, and 210Po in the dissolved and particle-bound phases of
      Irish Sea water.

PMID- 11838695
TI  - Use of a Plackett-Burman design with multivariate calibration for the analysis of
      polycyclic aromatic hydrocarbons in micellar media by synchronous fluorescence.
AB  - This work describes the use of a multilevel Plackett-Burman design (PB) for the
      creation of a calibration set for partial least square regression (PLS). The PB
      calibration set was compared to a collinear analogue by testing these two PLS
      models for the analysis of six polycyclic aromatic hydrocarbons (PAHs). These
      compounds were analyzed in micellar media by synchronous fluorescence after
      determination of the experimental conditions (choice of surfactant, analytical
      conditions such as deltalambda, step, and scan range). The external validation
      shows that the collinear set is inappropriate to quantify PAH in real samples,
      but the PB calibration set affords optimal results.

PMID- 11838696
TI  - Standardizing food analysis.

PMID- 11838697
TI  - Accuracy estimation of multiangle light scattering detectors utilized for
      polydisperse particle characterization with field-flow fractionation techniques:
      a simulation study.
AB  - The coupling of field-flow fractionation (FFF) and multiangle light scattering
      (MAIS) detectors is complementary in that the MALS system allows particle
      characterization when a narrow dispersity particle population is present in the
      detector. The fractionation process provides this narrow dispersity. Utilizing
      discrete particle simulations of FFF and optical calculations based on both the
      Mie theory of particle scattering and Rayleigh-Gans-Debye (RGD) scattering
      theory, the extent of polydispersity that can be tolerated for accurate particle
      quantitation is explored. It is found that flow, electrical, and sedimentation
      FFF provide adequate separation for accurate particle quantitation by MALS. The
      Mie theory is more accurate than the RGD theory, which is known to deviate at
      higher particle size. Low error in the measurement of mean diameters is found
      when only the particle diameter is of interest. It is shown that the
      reconstruction of the particle size distribution from time slice data is
      distorted due to errors in concentration, which result from finite polydispersity
      and other effects. A number of procedures are evaluated in restoring the size
      distribution to higher accuracy. None of these procedures is deemed of general
      purpose and none of these is reliable. The best results are obtained when
      fractionation is conducted under the minimal possible outlet polydispersity and
      when steric effects are minimized. In addition, best results are had for
      inherently narrow dispersity colloidal materials.

PMID- 11838698
TI  - Theoretical understanding of an absorption-based surface plasmon resonance sensor
      based on Kretchmann's theory.
AB  - An optical-absorption-based surface plasmon resonance (SPR) sensor is proposed,
      and its theoretical aspects are discussed in terms of mathematical descriptions
      and numerical simulations of the SPR curve. The response theory of the absorption
      based SPR sensing is based on the expansion of Kretchmann's SPR theory into the
      case in which optical absorption in the sensing layer is expressed by the Lorentz
      model. The numerical simulations were performed using a three-layer Fresnel
      equation of p-polarization. It was found that SPR curve behavior of the
      absorption-based SPR sensor depends on the frequency relation between the light
      source and the optical absorption and the thickness of the metal layer. The SPR
      curve behavior is divided into three types according to the large, small, and
      equal relations between excitation and absorption frequencies. Each type of
      behavior is further divided into two types that are due to thin and thick metal
      layers. The theory of this new type of sensor based on optical absorption was
      explained and demonstrated by the simulation of the SPR curves using optical
      parameters relating to a silver-metal-based SPR sensor.

PMID- 11838699
TI  - Imprinting of nucleotide and monosaccharide recognition sites in
      acrylamidephenylboronic acid-acrylamide copolymer membranes associated with
      electronic transducers.
AB  - Molecular recognition sites for the nucleotides adenosine 5'-monophosphate (1),
      guanosine 5'-monophosphate (2), cytosine 5'-monophosphate (3), and uridine 5'
      monophosphate (4) are imprinted in an acrylamide-acrylamidephenylboronic acid
      copolymer (5) membrane. The imprinted membranes are assembled on piezoelectric Au
      quartz crystals or Au electrodes via electropolymerization or on the gate surface
      of an ISFET device by radical polymerization. The imprinted membranes reveal
      selectivity toward the imprinted nucleotide, and the association of the
      respective nucleotides with the recognition sites is transduced by the following:
      (i) microgravimetric, quartz crystal microbalance (QCM) measurements; (ii)
      Faradaic impedance analyses, and (iii) potentiometric responses of the ISFET
      devices. While the microgravimetric QCM measurements reflect the swelling of the
      polymers upon the association of the nucleotides with the recognition sites, the
      ISFET response is due to the charging of the polymer membrane as a result of the
      formation of the nucleotide-boronate complex. The selective detection of the
      nucleotides may lead to new DNA/RNA sequencing methods. Also, specific
      recognition sites for beta-D(+)-glucose (6), D(+)-galactose (7), and beta-D(-)
      fructose (8) were imprinted in an acrylamide-acrylamidephenylboronic acid
      copolymer (5) membrane associated with an ISFET device. Selective sensing of the
      respective monosaccharides is accomplished in the presence of the imprinted
      membrane-functionalized ISFET devices.

PMID- 11838700
TI  - The physics of laser ablation in microchemical analysis.

PMID- 11838701
TI  - Integrating waveguide biosensor.
AB  - A capillary biosensor is demonstrated which uses the waveguiding properties of
      the capillary to integrate the signal over an increased surface area without
      simultaneously increasing the background noise from the detector. This biosensor
      achieves limits of detection of 30-50 pg/mL in immunoassays using a diode laser
      for excitation and a PMT for detection. This is approximately 2 orders of
      magnitude greater sensitivity than was achieved using the same immunoassay
      reagents in a fiber optic biosensor or a planar array biosensor. Two different
      approaches to using the capillaries as immunosensors are described, either of
      which could be adapted for multianalyte sensing.

PMID- 11838702
TI  - Easily constructed spectroelectrochemical cell for batch and flow injection
      analyses.
AB  - The design and performance of an easily constructed spectroelectrochemical cell
      suitable for batch and flow injection measurements are described. The cell is
      fabricated from a commercially available 5-mm quartz cuvette and employs 60 ppi
      reticulated vitreous carbon as the working electrode, resulting in a reasonable
      compromise between optical sensitivity and thin-layer electrochemical behavior.
      The spectroelectrochemical traits of the cell in both batch and flow modes were
      evaluated using aqueous ferricyanide and compare favorably to those reported
      previously for similar cells.

PMID- 11838703
TI  - Plastic advances microfluidic devices.

PMID- 11838704
TI  - The SFC comeback. Pharmaceuticals give supercritical fluid chromatography a
      fighting chance.

PMID- 11838705
TI  - CE on the web.

PMID- 11838706
TI  - Roles of caspases in the programmed cell death of motoneurons in vivo.
AB  - Cysteine proteases comprising the caspase family have been considered one of the
      major executioners of programmed cell death. However, detailed analyses of the
      programmed cell death of developing motoneurons in mice following the genetic
      deletion of two key caspases, casp-3 and casp-9, and in the chick embryo
      following treatment with caspase inhibitors, indicate that normal amounts of cell
      loss occur although the death process is delayed. Motoneurons undergoing
      programmed cell death without caspase activities exhibit a nonapoptotic
      morphology in which nuclear changes such as chromatin condensation are absent or
      reduced and which exhibit extensive cytoplasmic vacuolization such as is rarely
      observed in degenerating control neurons. These results suggest that caspases are
      involved in, but are not indispensable for, the developmental death of
      motoneurons, and that one function of caspases may be to facilitate the removal
      of cells that are destined to die. Possible alternative caspase-independent
      pathways for the programmed death of motoneurons are discussed.

PMID- 11838707
TI  - Three-dimensional structure of G-banded human metaphase chromosomes observed by
      atomic force microscopy.
AB  - The structure of G-bands in human metaphase chromosomes was analyzed by
      comparison between light microscopic and atomic force microscopic (AFM) images of
      the same chromosomes. G-bands of the chromosomes were made by trypsin treatment
      followed by staining with a Giemsa solution. The banded chromosomes examined by
      light microscopy were dried either in air or in a critical point-drier, and
      observed by non-contact mode AFM. Air-dried chromosomes after G-band staining
      showed alternating ridges and grooves on their surface, which corresponded to
      light-microscopically determined G-positive and G-negative bands, respectively.
      At high magnification, the G-positive ridges were composed of densely packed
      chromatin fibers, while the fibers were loose in the G-negative grooves. Fibers
      bridging the gap between sister chromatids of a mitotic pair were often found,
      especially in the G-positive portions. These findings suggest that the G-banding
      pattern reflects the high-order structure of human metaphase chromosomes.

PMID- 11838708
TI  - Phosphatase activities of rat intestinal enterocytes and their relation to
      diverse luminal pH, with special references to the possible localization of
      phytase along the brush border membrane.
AB  - Phosphatase activities associated with the intestinal brush border membrane (BBM)
      of the rat were examined histochemically in relation to the characteristic
      environment of the intestine, where luminal pH fluctuates drastically between
      alkaline and acid pH ranges. Special attention was given to intestinal alkaline
      phosphatase (IALP) and phytase on the BBM. Whole body fresh-frozen sections of
      young rats and their rapidly frozen and freeze-substituted small intestines,
      embedded in Technovit 7100, were processed for the histochemical demonstration of
      phosphatase activity at three different pH values (9.2, 7.3, and 5.2),
      representing the deviation of luminal pH in vivo. Either an azo-dye method or
      lead-salt method was employed using naphthol AS-MX phosphate and ATP as
      substrate, respectively. With the azo-dye method, intense phosphatase reactions
      were demonstrated along the BBM at all three pH ranges. Phosphatase reactions of
      the BBM at pH 9.2 and 7.3 were abolished by L(+)-phenylalanine, heat pre
      treatment, and EDTA chelation although some reaction remained at pH 7.3 after the
      treatment with EDTA or L(+)-phenylalanine. Phosphatase reactions of the BBM at pH
      5.2 were resistant to L(+)-phenylalanine, L(+)-tartrate, PCMB and EDTA chelation,
      implying that the characteristics of the enzyme responsible for phosphohydrolysis
      at acid pH values differed from those at higher pH values. The lead-salt method
      in which ATP was used as substrate revealed intense reactions--which were
      dependent on Mg++ and stimulated by Ca++ and resistant to L(+)phenylalanine--to
      be localized along the BBM at alkaline and neutral pH values, but not at acid pH
      values. In vitro experiments showed progressive hydrolysis of naphthol AS-MX
      phosphate by purified phytase at pH 5.2, in a dose-dependent manner, and
      suggested the possible involvement of phytase in the phosphatase reactions of the
      BBM at acid pH. These data indicate that the phosphatase reactions at alkaline
      and neutral pH values, associated with the BBM of the rat intestine, represent
      IALP and Mg++/ Ca++-ATPase, while those at acid pH appear to correspond to
      phytase activity, something which has not been demonstrated by histochemical
      methods despite the availability of extensive data based on biochemical analyses.

PMID- 11838709
TI  - Responses of odontoblasts to cavity preparation in rat molars as demonstrated by
      immunocytochemistry for heat shock protein (Hsp) 25.
AB  - Responses of odontoblasts to cavity preparation in rat molars were investigated
      by immunocytochemistry for heat shock protein (Hsp) 25. In untreated control
      teeth, intense Hsp 25-immunoreactivity was found in the cell bodies of
      odontoblasts and their processes within the predentin. Confocal microscopy of Hsp
      25-immunostained and rhodamine-labeled sections revealed that the immunoreactive
      odontoblasts were intensely labeled for phalloidin at the periphery of their
      cytoplasm and throughout their processes, but the reaction for phalloidin was
      limited within the inner half of the dentin. Cavity preparation caused an
      edematous reaction between the injured odontoblasts and predentin as well as a
      beaded swelling and successive destruction of the odontoblast processes.
      Immediately after cavity preparation, the odontoblasts beneath the edematous
      lesion showed an immunoreactivity for Hsp 25, which subsequently disappeared
      completely from the pulp-dentin border by 12 h after the operation. However,
      round cells without apparent cytoplasmic processes continued to be
      immunoreactive, suggesting the survival of a part of the odontoblasts against
      preparation stimuli. Numerous phalloidin-reactive but Hsp 25-immunonegative cells
      appeared along the pulp-dentin border and extended their processes deep into the
      exposed dentinal tubules, probably categorized in a lineage of immunocompetent
      cells. By postoperative 72 h, newly differentiated odontoblasts with Hsp 25
      immunoreactivity were arranged at the pulp-dentin border. These findings indicate
      that the time course of changes in the expression of Hsp 25-immunoreactivity
      reflects the regeneration process of odontoblasts, and suggest that this protein
      is a useful marker substance for differentiated odontoblasts.

PMID- 11838710
TI  - The exact expression of glial fibrillary acidic protein (GFAP) in trigeminal
      ganglion and dental pulp.
AB  - The expression in various cell types of peripheral tissues of glial fibrillary
      acidic protein (GFAP), first discovered as an intermediate filament specific for
      astrocytes, remains controversial owing to numerous reports of a wide
      distribution for GFAP-immunoreactivity in various cells. The present study
      employed immunohistochemistry to investigate the precise expression of GFAP in
      the dental pulp and trigeminal ganglion of adult rats and wild-type mice as well
      as GFAP-knockout mice. The exhibition of GFAP-immunoreactivity in the trigeminal
      ganglion was further examined by a reverse transcription polymerase chain
      reaction (RT-PCR) technique, and in situ hybridization histochemistry using a
      specific cRNA probe prepared by us. The immunoreaction for GFAP was recognizable
      in the axons, Schwann cells, and the fibroblasts in the dental pulp of rats and
      wild-type littermate mice. However, mice with null mutations in the GFAP gene
      remained immunoreactive for GFAP in all these locations. Intense GFAP
      immunoreactivity was found in a small number of satellite cells in the trigeminal
      ganglion in all animals examined in this study. RT-PCR analysis demonstrated
      bands for the GFAP gene corresponding to the length expected from the primer
      design in the samples of trigeminal ganglion and dental pulp. In situ
      hybridization histochemistry also showed intense signals for GFAP mRNA in some
      satellite cells of the trigeminal ganglion, but never in the neurons. These data
      suggest that the GFAP-immunoreactive molecules in the pulpal axons and
      fibroblasts react non-specifically with the polyclonal antibody and are probably
      a closely related type of intermediate filament.

PMID- 11838711
TI  - Postnatal development of lymphatic vessels and their smooth muscle cells in the
      rat diaphragm: a confocal microscopic study.
AB  - This paper reports on how lymphatic vessels and their smooth muscle cells develop
      in the diaphragm of postnatal rats. Lymphatic endothelial cells in the diaphragm
      were labeled by an intraperitoneal injection of DiI-labeled acetylated low
      density lipoprotein (DiIac-LDL). During postnatal week 1, DiI-ac-LDL was detected
      in many free cells in addition to distinct endothelial cells that formed
      lymphatic vessels. Occasionally, saccular lymphatics isolated from previously
      formed lymphatics were recognized; these were referred to as lymphatic islands.
      The DiI-ac-LDL-labeled free and lymphatic endothelial cells showed
      immunoreactivity for CD 34 and Flt-4, but most of them did not express either OX
      62 or ED 1 immunoreactivity, with only some showing ED 1 immunoreactivity. This
      suggests that most of the DiI-ac-LDL-labeled elements were lymphatic endothelial
      cells, and that some were macrophages. After postnatal week 1, the DiI-ac-LDL
      positive cells were restricted to lymphatic vessels. Until postnatal week 6,
      lymphatic vessels increased as the diaphragm enlarged. Towards the end of
      postnatal week 2, free cells expressing alpha-smooth muscle actin (alpha-SMA)
      immunoreactivity increased in the diaphragm, and some of these were in contact
      with lymphatics. A coarse plexus of smooth muscle cells surrounding the lymphatic
      vessels first appeared at postnatal week 2, and this plexus became denser with
      age. Our findings indicate that lymphatic vessels are formed not only by
      sprouting from previously formed lymphatic vessels but also by migrating
      endothelial cells, and that smooth muscle cells may be differentiated from
      mesenchymal cells to form a plexus surrounding the lymphatic vessels.

PMID- 11838712
TI  - Development of the lymphatic network in the muscle coat of the rat jejunum as
      revealed by enzyme-histochemistry.
AB  - The process of lymphangiogenesis was studied in the muscle coat of the rat small
      intestine by light and scanning and transmission electron microscopy;
      identification of lymphatic vessels was made by 5'-nucleotidase staining. Light
      and scanning electron microscopy demonstrated that the intramuscular lymphatic
      network formation, which started only postnatally, was attributable to the
      vascular sprouting of slender lymphatic endothelial projections and to a
      splitting of the vessels, causing intervascular meshes of various sizes. The
      growing lymphatics were consistently closed by the endothelial cells, which were
      characterized by an abundance of cell organelles and prominent cytoplasmic
      processes. The cells often revealed close contacts with the processes of
      developing smooth muscle cells in the jejunal muscle coat, suggesting a possible
      role for the latter cells in the guidance of the lymphatic extension. The present
      study is the first to suggest the closed nature of lymphatics persisting
      throughout their development, even at the initial stage of lymphangiogenesis.

PMID- 11838713
TI  - Chondroitin sulfate proteoglycan at the basal lamina beneath high endothelial
      cells in human palatine tonsils: a light and electron microscopic study using the
      cationic colloidal iron method.
AB  - The basal lamina of high endothelial venules (HEVs) in human palatine tonsils was
      intensely stained with cationic colloidal iron at pH 1.5 and with aldehyde
      fuchsin. This basal lamina exhibited a thick and double- or triple-layered
      structure forming small compartments, in which many lymphocytes were aligned.
      Digestion with hyaluronidase or collagenase eliminated both the colloidal iron
      and aldehyde fuchsin stainings of the basal lamina of HEVs. Treatment with
      chondroitinase ABC reduced colloidal iron staining, but did not interfere with
      the aldehyde fuchsin staining. Digestion with neuraminidase, keratanase, or
      heparitinase did not eliminate either the cationic colloidal or the aldehyde
      fuchsin staining. Digestion with neuraminidase reduced the colloidal iron
      staining on the luminal surface coat of the HEV. Electron microscopy of ultrathin
      sections revealed that cationic colloidal iron particles were deposited on the
      basal lamina of the HEV. The basal laminae of ordinary blood vessels were thin
      and single-layered, and stained only weakly with cationic colloidal iron. The
      present study suggests that negatively charged sites in the basal lamina of HEV
      derive mainly from a proteoglycan complex containing hyaluronic acid and
      chondroitin sulfate, which firmly binds collagen. This topochemical feature is
      suggested to be involved in the fascilitating migration of lymphocytes after
      passage through the endothelial layer.

PMID- 11838714
TI  - Developmental changes in the fine structure and histochemical properties of
      mucous cells in the parotid gland of the infant Japanese macaque.
AB  - Mucous cells have been known to occur in the terminal portions of the parotid
      gland in a few species of mammals during a limited period of their development.
      The aim of this study was to examine the occurrence and features of mucous cells
      in the parotid gland of the infant Japanese macaque. Light microscopy revealed
      that mucous cells in the macaque parotid gland were present in the terminal
      clusters and acini at postnatal day 15, were less prevalent at day 30, and
      continued to decrease in number over 3 months. Mucous cells were no longer
      recognized in the parotid gland in 6-month-old macaques. Electron microscopy
      showed that the mucous cells contained electron-lucent secretory granules and
      bipartite or tripartite secretory granules. By 3 months of age, there was a
      scarcity of mucous cells and a concomitant increase in transitional cells. These
      transitional cells were intermediate in structure between mucous and serous
      cells, and contained three types of granules: electron-lucent, bipartite or
      tripartite, and electron-dense. None of the cells showed apoptotic figures.
      Lectin histochemistry indicated that the mucous cells in the early postnatal
      period had sugar residues identical in nature to those seen in the granules from
      mature serous cells in the glands of 3-month-old macaques. Immunohistochemistry
      using an antibody against human alpha-amylase showed a weakly positive reactivity
      in the secretory granules of the mucous cells, starting from day 15. In the
      transitional cells, the electron-dense granules showed a stronger
      immunoreactivity than either the electron-lucent granules or the heterogeneously
      structured granules. These results suggest that the secretory granules of mucous
      cells have characteristics in common with those of serous cells, and that during
      the transitional period the mucous granules change from the initial electron
      lucent to hetorogenous forms, finally becoming the electron-dense granules. The
      mucous cells in the parotid gland of the juvenile Japanese macaque are therefore
      suggested to be converted into serous cells.

PMID- 11838715
TI  - Translating instruments into other languages: development and testing processes.
AB  - Cross-cultural influences affect perceptions and health practices, which are 2
      areas of nursing concern. Culturally sensitive assessment instruments are needed,
      but many challenges exist in obtaining valid and reliable measurement.
      Translating questionnaires for cross-cultural research is fraught with
      methodological pitfalls related to colloquial phrases, jargon, idiomatic
      expressions, word clarity, and word meanings. It cannot be assumed that a
      particular concept has the same relevance across cultures. Simply translating an
      English version word-for-word into another language is not adequate to account
      for linguistic and cultural differences. Ideally, the perspectives of people from
      the culture about the concept of interest should be studied first, but often a
      practical alternative is to find and translate a tool developed in another
      culture. The purpose of this article is to describe important considerations in
      conducting translation for equivalence, types of equivalence, and strategies to
      translate instruments that promote equivalence and how to test the translated
      version for equivalence. These concepts and strategies are illustrated by
      describing the translation process of Hilton's Uncertainty Stress Scale into
      French and the use and testing of the French version with a French Canadian
      sample in Skrutkowski's study of perceived uncertainty in adult survivors of
      cancer.

PMID- 11838716
TI  - Genetic testing for cancer predisposition.
AB  - The onslaught of genetic innovations in the past decade has resulted in the
      ongoing identification of a spectrum of genes, some of which, when mutated,
      result in cancer susceptibility. The impact of these discoveries on healthcare
      provides an opportunity to enhance health promotion and long-term health outcomes
      by identifying at-risk individuals before cancer develops. This provides the
      healthcare provider with the potential to intervene much earlier to either reduce
      the risk or diagnose a cancer early when the chances for effective treatment are
      greatest. Even though genetic testing is increasingly being employed clinically,
      there remains a gap between the technology and effective interventions. Genetic
      tests also provide information that is distinct from other tests used routinely
      in health promotion, because of the personal and family nature of the
      information. This results in unique clinical, ethical, legal, and social issues
      that further affect the effective diffusion of this technology clinically. This
      article provides an overview of the distinguishing characteristics of genetic
      testing, outlines the essential components of informed consent, and discusses the
      potential implications of testing on individuals' lives and the nurse's role in
      offering genetic testing.

PMID- 11838717
TI  - Interest in genetic prostate cancer susceptibility testing among african American
      men.
AB  - Six regions for prostate cancer genes have been identified, and it is anticipated
      that prostate cancer susceptibility testing will be available in the future. This
      correlational study identified predictors for interest in prostate cancer
      susceptibility testing among African American men. Participants were 320 African
      American men from the African American Hereditary Prostate Cancer Study and the
      South Carolina Prostate Cancer Education and Screening Study participated. Two
      questions measured interest in genetic prostate cancer susceptibility testing and
      family history of prostate cancer. Chi-square analyses by family history as well
      as demographics (age, education, marital status) were performed. Most of the men
      (277 [87%]) indicated an interest in genetic prostate cancer susceptibility
      testing. Interest in undergoing testing did not vary by family history, age, or
      education. Marital status was the only significant demographic predictor. Men who
      were married were significantly more likely to respond with a "yes" to interest
      in prostate cancer susceptibility testing than were men who were not married. The
      high "yes" response rate and the men's confusion between the genetic prostate
      cancer susceptibility testing and prostate cancer screening highlight the need
      for public education once prostate cancer genes are identified and available for
      public testing.

PMID- 11838718
TI  - Information needs and information-seeking behaviors of men with prostate cancer
      and their partners: a review of the literature.
AB  - A critical review of the literature was carried out in the United Kingdom to
      identify the information needs and information-seeking behaviors of men with
      prostate cancer and their partners. Relevant papers published between 1990 and
      2000 were reviewed and despite having several methodologic limitations, a number
      of conclusions can still be drawn from this review. First, men with prostate
      cancer have distinct information needs and information-seeking behaviors
      throughout their cancer journeys. Although there is considerable variation in the
      amount and type of information that men require, the majority of men with
      prostate cancer are satisfied with the information they receive. Second, although
      partners of men with prostate cancer have needs for information, these needs are
      often unmet. Partners undergo an information-seeking pattern that is comparable
      with, if not more active than, patients' information-seeking behaviors. These
      findings have a number of implications for cancer nursing practice and research,
      which are discussed in the article.

PMID- 11838719
TI  - Assessing information and decision preferences of men with prostate cancer and
      their partners.
AB  - The purpose of this study was to identify and compare information and decision
      preferences of men with prostate cancer and their partners at the time of
      diagnosis. A convenience sample of 80 couples was recruited from The Prostate
      Centre in Vancouver, Canada. Participants used a computerized version of two
      previously used measures with this population: Control Preferences Scale and
      Information Survey Questionnaire. Results showed that men had a preference to
      play either an active or a collaborative role in decision making with their
      physician (92.5%) and partners (100%). The majority (55%) of partners wanted to
      play a collaborative role in treatment decision making. Couples identified
      prognosis, stage of disease, treatment options, and side effects as the top 4
      information preferences. Men ranked information on sexuality more important than
      partners, and partners ranked information on home self-care higher than men. Men
      who had sons, a positive family history, and lower levels of education ranked
      heredity risk significantly higher. Profiles of information categories did not
      differ according to role preferences of either men or partners. The computer
      program has been shown to be a reliable and acceptable method of assessing
      information and decision preferences of these couples. An individualized approach
      is suggested, given the high reliability of individual's profiles.

PMID- 11838720
TI  - Postmenopausal survivors of breast cancer at risk for osteoporosis: nutritional
      intake and body size.
AB  - Postmenopausal survivors of breast cancer for whom hormone replacement therapy is
      contraindicated are at risk for development of osteoporosis. The primary purpose
      of this article is to describe, in a sample of 30 postmenopausal survivors of
      breast cancer, their calcium and vitamin D intake compared with recommended
      dietary guidelines for those nutrients for postmenopausal women not taking
      hormone replacement therapy and the body mass index of these women as nutritional
      status risk factors for development of osteoporosis. Bone health and presence of
      osteoporosis were determined by bone mineral density testing of the spine, hip,
      and forearm. To obtain calcium and vitamin D intake, including supplements, 3-day
      diet records were completed; height and weight measures were used to calculate
      body mass index. The sample participants ranged in age from 42 to 65 years; the
      majority (56%) had been menopausal or off hormone replacement therapy for 5 years
      or less, and 70% had completed breast cancer treatment for 5 years or less
      (except tamoxifen). The majority (63%) were of medium body frame size; 30% were
      of small frame size. The mean body mass index (27.3) and mean weight (160 lbs)
      indicate that these women, as a group, were over-weight. Although a large percent
      (63%) were taking calcium supplements, the mean daily intake (diet and
      supplements) of calcium (1,353 mg) and vitamin D (403 IU) was less than the
      recommended dietary guidelines for these nutrients in this population. At study
      entry, 80% of the women were osteopenic (60%) or osteoporotic (20%) and none was
      receiving treatment/prevention for osteoporosis; only 1 had a previous known
      osteoporosis diagnosis. This is a special group of women for whom screening and
      preventive strategies for osteoporosis are imperative.

PMID- 11838721
TI  - The impact on sexual functioning of chemotherapy-induced menopause in women with
      breast cancer.
AB  - This article presents a comprehensive review and synthesis of empirical and
      conceptually based literature documenting the impact of chemotherapy-induced
      menopause on the sexual functioning of women with breast cancer. A literature
      search of the CINAHL, MEDLINE, and Psych Lit from 1980 to 1999 databases was
      undertaken. This literature was systematically assessed to determine key findings
      and conclusions. Two major themes were identified and are reported here: physical
      and psychological sequelae associated with altered sexual functioning.
      Recommendations and suggestions for further directions in research are
      identified.

PMID- 11838722
TI  - Families of children with cancer: the impact on anxiety experienced by fathers.
AB  - By using the contextual model of family stress, this study examined fathers'
      family stress experience when caring for a child receiving cancer treatments. A
      descriptive correlational study was designed to examine the relationships between
      fathers' uncertainty, sense of mastery, and anxiety. Eighty fathers were
      recruited from two teaching hospitals in Taiwan. A pilot study was conducted to
      establish the reliability and validity of the Chinese language version of the
      above instruments. These instruments showed an acceptable internal consistency
      and satisfactory construct validity. Results showed that fathers' level of
      education had a significant effect on paternal anxiety. Uncertainty and fathers'
      education level equal to or higher than university are good predictors of
      paternal anxiety, which explain 25% of the variance. The results provide insight
      into the paternal experience of family stress and suggest ways to improve family
      centered nursing interventions and thereby establish better family well-being.

PMID- 11838723
TI  - Health-related quality of life in pediatric patients with cancer. A structural
      equation approach with the Roy Adaptation Model.
AB  - The purpose of this study was to test the Roy Adaptation Model-based theory of
      health-related quality of life in Taiwanese children with cancer. The
      environmental stimuli included severity of illness, age, gender, communication
      with others, and understanding of the illness. The severity of the illness was
      considered as a latent variable construct, including the stage of illness,
      laboratory values, and number of hospitalizations. Biopsychosocial responses,
      that is health-related quality of life, was hypothesized as a latent variable
      that consisted of (1) physical function, (2) psychologic function, (3)
      peer/school func tion, (4) treatment/disease symptoms, and (5) cognition
      functions. In total, 102 children with cancer participated in the study.
      Structural equation modeling was used to examine 2 Roy Adaptation Model-based
      theory propositions. The findings showed that the construct of severity of
      illness demonstrated excellent fit with the stage of illness, laboratory values,
      and total number of hospitalizations. Second, the health-related quality of life
      also demonstrated good construct validity with 5 domains. Third, this study
      supported the Roy Adaptation Model-based theory proposition that environmental
      stimuli influenced biopsychosocial responses.

PMID- 11838724
TI  - Testing an instrument measuring Greek nurses' knowledge and attitudes regarding
      pain.
AB  - This pretest-post-test study was conducted to test the construct validity, test
      retest reliability, and internal consistency of the Nurses' Knowledge and
      Attitudes Survey Regarding Pain with Greek nurses. Forty-six registered nurses
      were randomly assigned to an expert or nonexpert group. The expert group viewed 4
      translated educational videotapes about pain management. The nonexpert group
      received no pain education. All of the nurses completed a pretest and a post-test
      using a Greek translation of the Nurses' Knowledge and Attitudes Survey Regarding
      Pain, with a time delay of 8 to 12 days between testing. The expert nurses
      learned significantly more than the nonexpert nurses from pretest to post-test, M
      = 9.0 and M = 1.5 items, respectively. Expert and nonexpert nurses correctly
      answered 51.5% and 43.3% of the pretest and 74.6% and 47.2% of the post-test
      questions, respectively. Test-retest reliability for the 28 nonexpert nurses was
      r = 0.68, P < .001. Cronbach's alpha for the entire sample was 0.88 (n = 30) at
      the post-test. These results contribute to the validity and reliability of the
      Greek version of the Nurses' Knowledge and Attitudes Survey Regarding Pain and
      provide the basis for phase II of the study, which will use the Nurses' Knowledge
      and Attitudes Survey Regarding Pain to examine the state of pain management in an
      anticancer facility in Greece.

PMID- 11838725
TI  - Severe and mild neonatal hypothyroidism mediate opposite effects on Leydig cells
      of rats.
AB  - The effects of neonatal hypothyroidism on the number of Leydig cells were studied
      in neonatal Wistar rats. Moderate or severe hypothyroidism were induced during
      neonatal life by giving different amounts of methimazole (MMI; 0.05% or 0.1%) in
      the drinking water of pregnant and lactating dams. Rats were sacrificed on day 21
      of postnatal life. Severely hypothyroid rats had approximately 45-fold higher
      serum thyrotropin (TSH) values and demonstrated approximately a 65% decrease in
      testes weight (p < 0.05) and the number of Leydig cells. However, in moderately
      hypothyroid rats, in which serum TSH was only approximately 16-fold higher,
      testicular weight was normal and the number of Leydig cells almost doubled (p <
      0.01). There were no significant differences between the serum-free testosterone
      levels of the moderately and severely hypothyroid rats versus controls. Serum
      levels of 3alpha-androstanediol glucuronide, although decreased to less than 10%
      in severely hypothyroid rats (p < 0.01), were not changed by mild hypothyroidism.
      The number of Sertoli cells was increased in moderately hypothyroid rats versus
      controls (p < 0.05) and even further increased in severely hypothyroid rats (p <
      0.05). We conclude that (1) severe neonatal hypothyroidism impairs the
      development and function of the testes and (2) moderate neonatal hypothyroidism
      stimulates the proliferation of Leydig cells.

PMID- 11838727
TI  - Apoptosis: life through planned cellular death regulating mechanisms, control
      systems, and relations with thyroid diseases.
AB  - Apoptosis is an active biologic process that represents a form of programmed
      cellular suicide, activated either by genetic factors or by cellular lesions
      caused by various extracellular traumatic agents. The alterations of its
      functional mechanisms control cellular homeostasis are involved in the genesis of
      many illnesses. There are different control systems that can both stimulate and
      inhibit apoptosis, such as the p53 and Bcl-2 proteins. Different injuries may
      cause a rapid increase in the levels of p53 and the activation of the complex
      mechanism which leads either to damage repair or cellular apoptosis. The concept
      of tumor growth as a dynamic balance between cellular development and death is
      well applicable to differentiated thyroid carcinomas, which are generally not
      highly invasive and present excellent prognosis. On the contrary, in aggressive
      anaplastic thyroid carcinoma there is an increase in p53, whereas in normal
      thyroid cells there is a high expression of Bcl-2, so as to interfere with
      apoptosis when physiologic hormone levels are normal. However, only some of the
      biomolecular mechanisms behind the genesis of thyroid tumors have been explained,
      and the role of apoptosis in thyroid diseases has not been well defined. This
      review provides information about relationship between apoptosis and thyroid
      diseases.

PMID- 11838726
TI  - Transposition of the thyroid iodide uptake and organification system in
      nonthyroid tumor cells by adenoviral vector-mediated gene transfers.
AB  - Radioactive iodine (131I) is routinely used for the treatment of differentiated
      thyroid cancers. Attempts have been made to enlarge this therapeutic strategy to
      nonthyroid tumors by coupling radioactive iodide administration with transfer of
      the sodium iodide symporter (NIS) gene into target cells, for example with an
      adenoviral vector (AdNIS). Although efficient iodide uptake was achieved in the
      tumors treated with AdNIS, no therapeutic effect could be observed with 131I,
      most probably because the iodide retention time in the target cells was short. To
      circumvent this problem, we propose to organify the iodide taken up, as it occurs
      in the thyroid. We constructed a recombinant adenovirus encoding the human
      thyroperoxidase (TPO) gene under the control of the cytomegalovirus early
      promoter (AdTPO). Infection of nonthyroid tumor cells with this virus led to
      production of an enzymatically active protein. A significant increase in iodide
      organification could be observed in cells coinfected with both AdNIS and AdTPO in
      the presence of exogenous hydrogen peroxide. However, the levels of iodide
      organification obtained were too low to significantly increase the iodide
      retention time in the target cells.

PMID- 11838728
TI  - Graves' disease is a multi-system autoimmune disorder in which extra ocular
      muscle damage and connective tissue inflammation are variable features.

PMID- 11838729
TI  - Clinical comparison of whole-body radioiodine scan and serum thyroglobulin after
      stimulation with recombinant human thyrotropin.
AB  - Sensitive monitoring for thyroid cancer recurrence or persistence includes whole
      body radioiodine scanning (WBS) and measurement of serum thyroglobulin (Tg) after
      endogenous or exogenous thyrotropin (TSH) stimulation. We reviewed our experience
      using recombinant human thyrotropin (rhTSH) in 83 patients to compare the
      clinical relevance of a positive WBS and/or Tg. Ten patients had a positive WBS;
      eight of these patients had activity limited to the thyroid bed. rhTSH-stimulated
      Tg was 2 ng/mL or more in 25 and 5 ng/mL or more in 13 patients. Of the patients
      with a negative WBS, 11 of 20 patients with a Tg 2 ng/mL or more and 7 of 9
      patients with a Tg 5 ng/mL or more received therapy or further evaluation based
      on the Tg alone. Conversely, only 1 of 5 patients with a serum Tg less than 2
      ng/mL received therapy or further evaluation based on a positive WBS alone. Three
      of the patients who did not receive therapy or further evaluation, had subsequent
      negative WBS 10-12 months later, suggesting lack of clinically significant
      disease. Twenty patients had a negative WBS and serum Tg 2 ng/mL or more. Eleven
      of 20 patients had a Tg less than 5 ng/mL and 4 of these patients had further
      evaluation with a neck ultrasound. One patient had a biopsy-proven recurrence
      (rhTSH-stimulated Tg 4 ng/mL). Subsequent evaluations (> or = 6 months later)
      have been negative for 8 patients. Of the nine patients with a Tg 5 ng/mL or more
      and a negative WBS, 7 had further evaluation and 6 of 7 had identified disease.
      In summary, rhTSH-stimulated WBS and Tg are complementary, but Tg is a more
      sensitive indicator of disease recurrence or persistence. In our practice, an
      rhTSH-stimulated Tg greater than 4-5 ng/mL often resulted in further evaluation,
      while a Tg less than 4 ng/mL rarely resulted in further immediate evaluation.

PMID- 11838730
TI  - Effect of different starting doses of levothyroxine on growth and intellectual
      outcome at four years of age in congenital hypothyroidism.
AB  - To evaluate the effect of different initial levothyroxine (LT4) replacement doses
      on growth and intellectual outcome in patients with congenital hypothyroidism
      (CH) detected by neonatal screening program, the longitudinal growth and
      intelligence quotient (IQ) were assessed and compared at 4 years of age in 83
      patients with CH. The patients were divided into three groups according to the
      initial LT4 dose used: (1) group 1 (n = 42) received the previously recommended
      dose of 6.0-8.0 microg/kg per day; (2) group 2 (n = 21) received a dose of 8.1
      10.0 microg/kg per day; (3) Group 3 (n = 20) a dose of 10.1-15.0 microg/kg per
      day. The IQ, evaluated by the Wechsler Preschool and Primary Scale of
      Intelligence test at 4 years of age, was significantly higher in group 3 (IQ 98
      +/- 9) compared to group 1 (IQ 88 +/- 13; p < 0.05) but not compared to group 2
      (IQ 94 +/- 13). However, the IQs were below the normal range (< 85) in six
      patients from group 2 (28%), but in none of the patients from group 3 (p = 0.03).
      Patients from group 3, with severe CH at diagnosis, had an IQ (97 +/- 9) at 4
      years of age, which was not different from that of patients from the same group
      with moderate CH at diagnosis (IQ 99 +/- 9). Similar results were also observed
      in patients from group 2 however, mean IQ scores in these patients (93 +/- 12)
      were several points lower than those observed in patients from group 3 (95 +/-
      15). After the first month of treatment, optimal serum levels of thyroxine (T4)
      and free thyroxine (FT4) were achieved in all groups, however, only patients from
      group 3 were able to normalize thyrotropin (TSH) (group 1, 16.0 +/- 12.0; group
      2, 9.2 +/- 10.0; and group 3, 2.4 +/- 3.3 mU/L; p < 0.0001). Twelve patients from
      group 2 treated with an initial LT4 dose above 9 microg/kg per day were able to
      normalize TSH levels within the first 3 months of life and this resulted in a
      better IQ (97 +/- 16) compared to the remaining patients from the same group (IQ
      90 +/- 9). In the whole group of 83 patients the IQ at 4 years of age was
      positively correlated to both initial LT4 dosage (r = 0.27, p < 0.02) and FT4
      concentrations after the first month of treatment (r = 0.29, p < 0.02), and
      negatively correlated to TSH concentrations after the first month of treatment (r
      = -0.27, p < 0.02). No significant differences were observed in height, weight,
      head circumference, and bone age maturation among the three groups of patients.
      No clinical signs or symptoms of overtreatment were observed during follow-up in
      patients receiving the higher LT4 dosage. Our results indicate that high LT4
      starting doses rapidly normalize serum TSH concentrations resulting in an
      improvement of the IQ at 4 years of age, even in patients with severe CH at
      diagnosis. Growth and bone age maturation are not affected by such a high dose.

PMID- 11838731
TI  - 99mTc-MIBI radio-guided minimally invasive parathyroidectomy: experience with
      patients with normal thyroids and nodular goiters.
AB  - The surgical approach to primary hyperparathyroidism (HPT) is changing. In
      patients with a high probability to be affected by a solitary parathyroid adenoma
      (PA), a unilateral neck exploration (UNE) or a minimally invasive radio-guided
      surgery (MIRS) using the intraoperative gamma probe (IGP) technique have recently
      been proposed. We investigated the role of IGP in a group of 84 patients with
      primary HPT who were homogeneously evaluated before surgery by a single-day
      imaging protocol including 99mTcO4/MIBI subtraction scan and neck ultrasound (US)
      and then operated on by the same surgical team. Quick parathyroid hormone (QPTH)
      was intraoperatively measured in all cases to confirm successful
      parathyroidectomy. In 70 patients with scan/US evidence of a single enlarged
      parathyroid gland (EPG) and with a normal thyroid gland, MIRS was planned. In the
      other 14 patients, the IGP technique was utilized during a standard bilateral
      neck exploration (BNE) because of the presence of concomitant nodular goiter (11
      cases) or multiglandular disease (MGD) (3 cases). The IGP technique consisted of
      the following: (1) in the operating room, a low 99mTc-MIBI dose (37 MBq) was
      injected intravenously during anesthesia induction; (2) subsequently, the
      patient's neck was scanned with the probe by the surgeon to localize the
      cutaneous projection of the EPG; (3) in patients who underwent MIRS, the EPG was
      detected intraoperatively with the probe and removed through a small, 2 to 2.5 cm
      skin incision; (4) radioactivity was measured on the EPG both in vivo and ex
      vivo, the thyroid, the background and the parathyroid bed after EPG removal. In
      patients with concomitant nodular goiter, the radioactivity was also measured on
      the thyroid nodules. Surgical and pathologic findings were consistent with a
      single PA in 78 patients, parathyroid carcinoma in 2, and MGD in 4. MIRS was
      successfully performed in 67 of the 70 patients (97.7%) in whom this approach was
      planned. It must be pointed out that the IGP technique was particularly useful in
      detecting the PAs located in ectopic site (5 in the upper mediastinum, 2 at the
      carotid bifurcation) and deep in the neck (6 in the paratracheal/paraesophageal
      space). Moreover, MIRS was also successfully performed in the seven patients who
      had undergone previous parathyroid or thyroid surgery. In the other 3 of 70
      patients (4.3%), a conversion to BNE was required because a parathyroid carcinoma
      (2 cases) and a MGD (1 case) were diagnosed during surgical intervention. It is
      worth noting that in this latter patient affected by MGD, in contrast with the
      other patients from our series, QPTH remained elevated after the removal of the
      preoperatively visualized EPG suggesting the persistence of occult
      hyperfunctioning parathyroid tissue, and another contralateral EPG was found at
      BNE. Regarding the group of patients in whom a BNE was planned, the IGP helped
      the surgeon to localize a supernumerary EPG ectopic in the thymus in a patient
      with MGD, and to localize a PA ectopic to the right carotid bifurcation in a
      patient with nodular goiter. However, it has to be pointed out that it was
      difficult for the surgeon to differentiate intraoperatively with the probe the
      radioactivity of the EPG from that of thyroid nodule(s) in the other 10 patients
      with HPT with a concomitant nodular goiter, particularly in 6 patients in whom
      99mTc-MIBI uptake was higher in thyroid nodule(s) than in EPG. On the basis of
      these data we can conclude that: (1) in patients with primary HPT with a high
      scan/US probability to be affected by a single PA and with a normal thyroid
      gland, IGP appears to be an useful technique with the aim of performing MIRS; (2)
      a 99mTc-MIBI dose as low as 37 MBq appears to be adequate to successfully perform
      MIRS; (3) the measurement of QPTH is strongly recommended in patients with HPT
      selected for MIRS to confirm complete removal of hyperfunctioning parathyroid
      tissue; (4) MIRS can be useful also in patients with HPT who previously received
      parathyroid/thyroid surgery with the aim of limiting surgical trauma at
      reoperation and minimizing the related risk of complications; (5) with the
      exception of PA located in ectopic sites, IGP does not seem to be a recommendable
      technique in patients with HPT concomitant nodular goiter.

PMID- 11838732
TI  - Overt and subclinical hypothyroidism complicating pregnancy.
AB  - We studied the evolution of 150 pregnancies corresponding to 114 women (16-39
      years old) with primary hypothyroidism. Fifty-one pregnancies (34%) were
      conceived under hypothyroidism: 16 overt (X +/- standard deviation [SD],
      thyroxine [T4]: 2.44 +/- 0.7 microg/dL; thyrotropin [TSH]: 33.4 +/- 8.82 mIU/L),
      and 35 subclinical hypothyroidism (T4: 6.93 +/- 1.88 microg/dL; TSH: 12.87 +/-
      8.43 mIU/L); 99 pregnancies were conceived under euthyroidism while undergoing
      thyroid therapy. When treatment with levothyroxine was inadequate, the outcome of
      pregnancy was abortion in 60% of overtly hypothyroid patients and in 71.4% of
      subclinically hypothyroid patients, premature delivery in 20% and 7.2%
      respectively, and term delivery in 20% and 21.4%, respectively. When treatment
      was adequate, 100% of overtly hypothyroid patients and 90.5% of subclinically
      hypothyroid patients carried pregnancies to term; there were no abortions in any
      of the groups. Abortions, premature and term deliveries in patients who were
      euthyroid on levothyroxine at the time of conception were 4%, 11.1% and 84.9%
      respectively. Of the patients receiving levothyroxine therapy before conception,
      69.5% had to increase the dose (mean increase 46.2 +/- 29.6 microg/d). Of 126
      evaluated newborns, 110 were delivered at term while 16 were premature. Eight
      newborns, 4 were premature, had congenital malformations (6.3%), and 4 died. Our
      results show that the evolution of pregnancies did not depend on whether the
      hypothyroidism was overt or subclinical but mainly on the treatment received. The
      adequate treatment of hypothyroidism during gestation minimizes risks and
      generally, makes it possible for pregnancies to be carried to term without
      complications.

PMID- 11838733
TI  - Smoking as a risk factor for Graves' disease, toxic nodular goiter, and
      autoimmune hypothyroidism.
AB  - To study the association between smoking and thyroid disease (Graves' disease
      [E05.0], nodular toxic goiter [E05.2], and autoimmune hypothyroidism [E03.9]) in
      a low-iodine intake area a case-control study was undertaken. A self-administered
      questionnaire was issued to 864 consecutive patients with hyperthyroidism and 628
      patients with autoimmune hypothyroidism treated at five university or regional
      endocrinologic clinics in Denmark between January 1, 1990 and December 31, 1998.
      Each respondent was compared to an age- (+/- 5 years) and gender-matched normal
      control person randomly drawn from the background population. A total of 621
      patients with hyperthyroidism (72%) and 411 patients with autoimmune
      hypothyroidism (66%) responded. Of these, 617 (542 females) and 408 (364 females)
      could be analyzed, respectively. There was an increased risk of both Graves'
      disease (odds ratio [OR] = 2.5, 95% confidence interval [CI]: 1.8-3.5), toxic
      nodular goiter (OR = 1.7, 95% CI: 1.1-2.5), and autoimmune hypothyroidism (OR =
      1.5, 95% CI: 1.1-2.1) with ever smoking compared to never smoking in women, but
      not in men. With the high proportion of ever-smokers among women (56%), the
      attributable risk of smoking in women was 45% in Graves' disease, 28% in toxic
      nodular goiter, and 23% in autoimmune hypothyroidism. Ever use of oral
      contraceptives was associated with a slightly lower risk of Graves' disease in
      women, but not of toxic nodular goiter or autoimmune hypothyroidism. In
      conclusion, smoking is a powerful risk factor for thyroid disease, especially in
      populations with a high smoking frequency. Oral contraceptive use is associated
      with a slightly lower frequency of Graves' disease.

PMID- 11838734
TI  - Selective uptake of p-borophenylalanine by undifferentiated thyroid carcinoma for
      boron neutron capture therapy.
AB  - Undifferentiated thyroid carcinoma (UTC) lacks an effective treatment. Boron
      neutron capture therapy (BNCT) is based on the selective uptake of 10B-boronated
      compounds by some tumors, followed by irradiation with an appropriate neutron
      beam. The radioactive boron originated (11B) decays releasing 7Li, gamma rays and
      alpha particles, and these latter will destroy the tumor. In order to explore the
      possibility of applying BNCT to UTC we have studied the biodistribution of BPA.
      In in vitro studies, the uptake of p-10borophenylalanine (BPA) by the UTC cell
      line ARO, primary cultures of normal bovine thyroid cells (BT), and human
      follicular adenoma (FA) thyroid was studied. No difference in BPA uptake was
      observed between proliferating and quiescent ARO cells. The uptake by quiescent
      ARO, BT, and FA showed that the ARO/BT and ARO/FA ratios were 4 and 5,
      respectively (p < 0.001). In in vivo studies, ARO cells were transplanted into
      the scapular region of NIH nude mice, and after 2 weeks BPA (350 or 600 mg/kg
      body weight) was injected intraperitoneally. The animals were sacrificed between
      30 and 150 minutes after the injection. With 350 mg, tumor uptake was highest
      after 60 minutes and the tumor/normal thyroid and tumor/blood ratios were 3 and
      5, respectively. When 600 mg/kg body weight BPA were administered, after 90
      minutes the tumor/blood, tumor/normal thyroid, and tumor/distal skin ratios for
      10B concentrations per gram of tissue were approximately 3, showing a selective
      uptake by the tumor. The present experimental results open the possibility of
      applying BNCT for the treatment of UTC.

PMID- 11838735
TI  - Thyrotoxicosis and paraparesis in a young woman: case report and review of the
      literature.
AB  - We describe a 23-year-old woman with a 3-week history of episodic leg weakness.
      The onset of weakness always occurred in the evening after dinner and the attacks
      resolved spontaneously by morning. Physical examination revealed a resting
      tachycardia and symmetrical, proximal weakness involving both arms and legs.
      Electrocardiogram (ECG) and electrolyte analysis showed a severe hypokalemia and
      thyroid function tests showed hyperthyroidism. The patient was diagnosed as
      having Graves' thyrotoxicosis and thyrotoxic periodic paralysis (TPP) and was
      initially treated with propranolol and subsequently carbimazole. No recurrence of
      the paralysis has been noted. TPP is most common in males of Asian extraction and
      is rare in women even in the Asian population. With increasing immigration, TPP
      is likely to occur more frequently in both Europe and North America and awareness
      of the condition is vital. Treatment of the underlying thyroid dysfunction cures
      the muscle symptoms.

PMID- 11838736
TI  - Resistance to thyroid hormone in a patient without thyroid hormone receptor
      mutations.
AB  - Resistance to thyroid hormone (RTH) is a clinical syndrome characterized by
      elevated serum thyroid hormone (TH) levels, unsuppressed thyrotropin (TSH)
      levels, and tissue hyposensitivity to TH. In almost all cases, the genetic basis
      of RTH lies in mutation of one of the two TH receptor beta (TRbeta) alleles.
      Recently, patients from several families with phenotypic manifestations of RTH in
      the absence of TR mutations have been described. We report a case of a 31-year
      old woman who presented with goiter, tachycardia, elevated TH levels,
      unsuppressed TSH, and "inappropriately normal" levels of peripheral TH action
      markers. In two separate clinical evaluations, the patient exhibited typical
      clinical and biochemical evidence for peripheral and pituitary RTH. Surprisingly,
      reverse transcriptase-polymerase chain reaction (RT-PCR) of full-length TRalpha
      and TRbeta mRNAs, and genomic PCR using primers flanking exons encoding the
      carboxy-terminal region of TRbeta failed to demonstrate mutations in the TRalpha
      or TRbeta genes. It is likely that defects in the regulation of TR genes or
      mutations in transcriptional cofactors involved in TR signaling account for this
      patient's phenotype.

PMID- 11838737
TI  - Vocal cord muscle activity as a drawback to FDG-PET in the followup of
      differentiated thyroid cancer.

PMID- 11838738
TI  - Cryptic infertility and therapeutic options.
AB  - Too often infertile patients are given a "herd type" fertility investigation
      which ultimately leads to expensive, time consuming, and risky in vitro
      fertilization. However, attention to certain simple details available by non
      invasive methods, e.g., checking for premature luteinization, luteinized
      unruptured follicle syndrome, or performing the post-coital test at the
      appropriate interval, can lead to a quick solution of the infertility problem.
      Caution about persistent infertility related to iatrogenic factors, e.g.,
      development of poor post-coital tests or excessively thin endometrium from
      clomiphene citrate, or development of luteinized unruptured follicle syndrome or
      premature luteinization by taking follicle maturing drugs, or creating a hostile
      environment from taking follicle maturing drugs when the woman already made a
      mature follicle (and would have had a higher success rate with luteal phase
      support with progesterone) will help achieve pregnancies without necessarily
      proceeding to the most expensive and invasive procedure of in vitro
      fertilization. Finally, many wasted cycles of treatment could be avoided by
      including the simple but very important hypo-osmotic swelling test and
      measurement of sperm autoantibodies with the first initial semen analysis.

PMID- 11838739
TI  - Biochemical and body weight changes with metformin in polycystic ovary syndrome.
AB  - OBJECTIVE: To evaluate the long-term effects of metformin on biochemical
      variables and body weight in polycystic ovary syndrome (PCOS). METHOD: Fifteen
      obese PCOS patients that attended the university clinic were included to this
      prospective study. These patients used 1,500 mg of metformin daily for 12 months.
      RESULT: We found a statistically different decrease in mean body mass index
      (t:4,369), (p:0.0002) at the end of the 12 months. In contrast to that there were
      no statistical differences in fasting serum insulin and testosterone levels.
      Metformin improved menstrual patterns (60% of cases) in obese PCOS patients.
      CONCLUSION: Hyperinsulinemia and androgen excess in obese non-diabetic women with
      PCOS are not improved by the administration of metformin. Metformin treatment may
      have improved menstrual patterns by a mechanism independent of and unrelated to
      insulin sensitivity or circulating insulin concentrations.

PMID- 11838740
TI  - Case report: successful pregnancy and delivery after myocardial infarction and
      essential thrombocythemia treated with clopidrogel.
AB  - We describe a case of a woman with essential thrombocythemia (ET) who had a
      subsequent successful pregnancy after a myocardial infarction and aortocoronary
      bypass grafting. We report the therapeutic management with clopidogrel and low
      molecular weight heparin. A healthy child was born spontaneously after 41 weeks
      of pregnancy. The placenta was morphologically normal. No maternal cardiac
      problems occurred.

PMID- 11838741
TI  - A case report demonstrating that follicle maturing drugs may create an adverse
      uterine environment even when not used for controlled ovarian hyperstimulation.
AB  - PURPOSE: To evaluate whether follicle maturing drugs used in lower dosages for
      luteal phase defects rather than controlled ovarian hyperstimulation may have an
      adverse effect on successful implantation. METHODS: Unique case report. RESULTS:
      A 40-year-old woman who failed to conceive after six years of follicle maturing
      drugs with or without progesterone supplementation and four years of in vitro
      fertilization with embryo transfer (92 embryos transferred in 10 cycles)
      successfully conceived with the first cycle after the exclusive use of vaginal
      progesterone in the luteal phase. CONCLUSIONS: This case provides convincing
      evidence that for some women follicle maturing drugs, even when used in lower
      dosages, can adversely affect the uterine environment.

PMID- 11838742
TI  - Gynaecological and obstetric audit at a G&O emergency department.
AB  - The present study takes into account only the patients that are sent home because
      their conditions do not require emergency hospitalization in order to try to
      understand the reasons why a woman seeks emergency treatment at a G&O emergency
      service.

PMID- 11838743
TI  - Marked improvement in clinical pregnancy rates following in vitro fertilization
      embryo transfer seen when transfer technique and catheter were changed.
AB  - PURPOSE: To compare in vitro fertilization (IVF) outcome with two different
      embryo transfer (ET) catheters: the Frydman and Wallace catheters. METHODS:
      Retrospective review of outcome of IVF cycles where there was at least one embryo
      that had assisted hatching prior to transfer at 72 hours according to which
      catheter was used. RESULTS: Pregnancy rate 17.6% per transfer with Frydman (FET
      SET) vs 44.2% for fresh ETs and 15.4% and 43.2% for frozen ETs. The implantation
      rates for fresh ETs were 7.6% vs 20.0% for fresh and 5.7 vs 21.1% for frozen ETs.
      CONCLUSION: The soft Wallace catheter is superior to the stiffer Frydman catheter
      when transferring embryos subjected to assisted embryo hatching.

PMID- 11838744
TI  - Human decidual cells can express the Hodgkin's cell-associated antigen Ki-1
      (CD30) in spontaneous abortions during the first trimester of gestation.
AB  - CD30 (Ki-1) antigen has been considered to be expressed on hematopoietic cells
      including the ones of the recently described anaplastic large cell lymphoma
      (ALCL), the Reed-Sternberg (RS) cells of Hodgkin's disease and the scattered
      large parafollicular cells in normal lymphoid tissues. Since then, several
      reports have been published describing CD30 expression in non-hematopoietic and
      malignant cells, such as cultivated human macrophages, human decidual cells,
      histiocytic neoplastic cells, mesothelioma cells, embryonal carcinoma, and
      seminoma cells. In the present study, we investigated the immunohistochemical
      expression of CD30 antigen in 15 paraffin-embedded placentas from fetuses after
      spontaneous abortion in the first trimester of gestation (8th, 10th, and 12th
      week, respectively) using the monoclonal antibody Ber-H2. All the pregnant
      patients had been given hormonal medication to support gestation. In addition, a
      panel of monoclonal antibodies for the identification of leukocytes (CD45/LCA), B
      lymphocytes (CD20/L-26), and T-lymphocytes (CD45RO/UCHLI) was performed. Our
      findings were correlated with those found in 15 placentas obtained from 15
      fetuses at the same time, after therapeutic or voluntary abortions. This study
      demonstrates that, 1) decidual endometrial stromal cells are able to express the
      CD30 (Ki-1) antigen, 2) the expression of CD30 in decidual cells is higher in
      cases of hormonal administration (to support gestation), than that found in
      normal gestation. In the former cases (hormonal support of gestation), a mild
      mononuclear infiltration of the decidua by UCHLI (T marker) positive cells,
      accompanies the CD30 positive cells.

PMID- 11838745
TI  - K statistic as a measure of quality control in cervicovaginal cytology.
AB  - Quality assessment schemes are widespread in most branches of pathology but are
      uncommon in the more subjective areas of histopathology and cytology. Researchers
      in many fields have become increasingly aware of the observer as an important
      source of measurement error. The validity of any method of reporting evidence of
      an abnormal process in cellular material is based on the degree of correlation
      with the actual disease process as it exists in the tissue and its
      reproducibility. Correlations can be tested in retrospective studies in which
      diagnoses based on cellular evidence are matched against the disease process
      present in biopsy specimens. Correlations can also be tested by examination of a
      set of unknown cellular preparations obtained in the presence of proven disease.
      While reproducibility is indirectly related to correlation, it is meant to imply
      satisfactory utilization of the method by other groups of cytotechnologists and
      cytopathologists. While cytopathology will continue to play an important role as
      a screening technique for the detection of cancer of the uterine cervix, its
      usefulness in the study of the early manifestations of the disease process is yet
      to be realized on a universal basis.

PMID- 11838746
TI  - Proposal for a novel and inexpensive surgical instrument to perform the tension
      free vaginal tape procedure in women with genuine stress incontinence.
AB  - The tension-free vaginal tape (TVT) technique is now commonly used in the
      management of female genuine stress incontinence. Short operation time, small
      amount of local anesthetic, fast postoperative mobilization, brief hospital stay,
      little residual urinary volume and little need for sick leave make TVT a simple
      and well-accepted minimal invasive surgery for the treatment of stress
      incontinence. We became suspicious of the procedure due to the very expensive
      cost of the instrumentation. Moreover we think that this "blind" procedure may be
      less dangerous by using a more familiar instrument than a large and gross steel
      needle. We propose the use of an unmodified procedure with a new, cheaper and
      easy-to-use steel clamp-like-instrument.

PMID- 11838747
TI  - Fetal tissue/organ transplant in HLA-randomized adult vascular subcutaneous
      axillary folds: preliminary report of 14 patients.
AB  - BACKGROUND: In the year 1902, the first successful experimental organ transplant,
      i.e., an autotransplant of a dog's kidney from its normal position to the vessels
      of the neck, which resulted in some urine flow, was performed in the Vienna
      Physiology Institute under the direction of Hofrath Exner by Dr. Emerich Ullman
      (1861-1937). Since then, the art of transplant surgery has come a long way in
      establishing itself as an important discipline with the support disciplines of
      immunology, molecular biology, etc., for the restoration of a failing organ.
      Today there is a major discrepancy in the demand and supply of organ grafts. The
      aim of the present study is to see whether fetal organ and tissue, with its
      intrinsic advantages of hypo-antigenicity, can survive in a HLA and sex
      randomized host in a surgically prepared vascular subcutaneous axillary fold,
      without any immunosuppressive support. We have earlier reported two cases of
      fetal thymic transplant, collected from consenting mothers undergoing hysterotomy
      and ligation. MATERIALS AND METHODS: Fourteen cases were recruited for the
      present study after thorough informed consent and approval by the Ethical
      Committee of the Project. Of these, five patients were suffering from advanced
      cancer, three from diabetic gangrene, three from ischaemic heart disease and
      three from rheumatoid arthritis, liver abscess and disc prolapse. The ages of the
      patients varied from 39 to 82 years. Six fetal thymuses, three fetal liver
      tissues, three fetal cardiac tissues, one fetal pancreas and one fetal lung
      tissue were transplanted. All the fetuses were dissected and the selected
      tissues/organs were transplanted within one to three minutes after collecting
      them from the consenting mothers undergoing hysterotomy and ligation. The fetal
      tissue graft was placed in a surgically prepared subcutaneous vascular axillary
      fold, 2x1 cm, under local anaesthesia in the consenting adult recipient.
      Sequential Hb, Tc, Dc, ESR were done to see the impact of the transplant on the
      host system. After one month, the transplanted fetal tissue was taken out by an
      elliptical incision and the tissue was processed for histological staining.
      RESULTS AND ANALYSIS: All the 14 patients tolerated the transplant procedure
      well. There was no fever, intractable pain or any other specific serious side
      effect justifying removal of the transplant earlier. There was no discharge from
      the incision site and the healing and scar were by and large normal. There was no
      unusual leucocytosis or lymphocytosis. The serial histological study did not
      suggest features of transplant rejection. DISCUSSION AND CONCLUSION: Pregnancy
      and neoplasm are two outstanding examples of natural tolerance to homograft. In
      both cases, blocking antibody has an important role in the phenomenon of
      immunotolerance. From our experiments mentioned above transplantation and our
      earlier reported studies, we believe that the hypo-antigenic fetal tissue has
      distinct advantages over adult tissue for transplant purposes.

PMID- 11838748
TI  - The conventional doses of human chorionic gonadotropins may not always be
      sufficient to induce ovulation in all women: a reappraisal.
AB  - BACKGROUND: Failure of ovulation has occasionally been reported following the
      administration of conventionally recommended doses of exogenous human chorionic
      gonadotropins. CASE: A 25-year-old nulliparous woman with polycystic ovary
      syndrome underwent ovulation induction for primary infertility. Following
      successful ovarian stimulation, she failed to ovulate during two consecutive
      cycles in response to human chorionic gonadotropin doses of 5,000 and 10,000 IU.
      When challenged with a higher than conventional dose (15,000 IU) on the third
      cycle, she ovulated and conceived. CONCLUSION: Conventional doses of exogenous
      human chorionic gonadotropins occasionally fail to complete the ovulatory process
      in some women. Women with polycystic ovary syndrome appear to be particularly
      susceptible. Routine documentation of ovulation and individualization of the dose
      of exogenous human chorionic gonadotropins could therefore prove to be useful in
      some of these women in order to achieve the best treatment outcome.

PMID- 11838749
TI  - Outcomes of carbon dioxide laser conization for the treatment of cervical
      intraepithelial neoplasia grade III.
AB  - PURPOSE: The aim of this study was to determine the rates of incomplete excision
      of cervical intraepithelial neoplasia (CIN) III after carbon dioxide laser
      conization, and the risk of reappearance of CIN depending on the excision
      margins. METHODS: A total of 153 women who underwent carbon dioxide laser
      conization for CIN III between 1988 and 1998 at our hospitals were eligible for
      inclusion in the study and their notes were retrospectively studied. RESULTS:
      Histological examination of the excision margins revealed complete excision in
      134 (87.6%), uncertain margins in one, and extension of CIN to the margins in 18
      (11.8%) cases. The treatment failure rate in the cases with clear margins was
      2.2% (3 of 134), and in the cases with involved margins 44.4% (8 of 18) (p <
      .001). CONCLUSION: Carbon dioxide laser conization despite the worldwide use of
      LLETZ still has a place in the treatment of CIN. Very high rates of complete
      excision were achieved. As incomplete excision does not always result in
      treatment failure, neither do clear margins always indicate eradication of the
      disease.

PMID- 11838750
TI  - Spinal versus general anesthesia for elective cesarean delivery: a prospective
      comparative study.
AB  - OBJECTIVE: To study the efficacy and safety of spinal anesthesia for elective
      cesarean section as compared with general anesthesia. PATIENTS AND METHODS: 175
      women undergoing elective cesarean section were studied prospectively. They were
      allocated into two groups; the first group (n=60) received spinal anesthesia, and
      the second one (n=115) received general anesthesia for elective cesarean section.
      Preoperative and intraoperative BP and IV fluids were recorded. Chi-Square and
      Fisher's exact tests were used to compare differences between the two groups; p <
      0.05 was considered significant. RESULTS: There were no differences between the
      two groups in terms of demographics, indication for elective cesarean section,
      operative time, gestational age, 1 and 5-min Apgar scores, and the means of
      preoperative and postoperative systolic and diastolic BP. A statistically
      significant increase was observed in terms of hypotension, postoperative
      analgesia, pre-induction and intraoperative IV fluids in the spinal group as
      compared to the general anesthesia group (p < 0.001, p < 0.01, and p < 0.01,
      respectively). CONCLUSION: Spinal anesthesia is as effective as a general
      anesthesia. Maternal and fetal outcome are favorable. Maternal hypotension can be
      managed successfully with modest doses of ephedrine and IV fluid infusions. It
      provides sufficient postoperative analgesia allowing the mother to have more
      vitality and comfort than those who receive general anesthesia.

PMID- 11838751
TI  - Neonatal magnetocardiography and Fourier spectral analysis.
AB  - OBJECTIVE: In this study we investigated the relationship between heart rate
      variability (HRV) and respiration in healthy and probably asphyxiated infants
      using magnetocardiographic (MCG) recordings. METHODS: Ten healthy and eight
      infants from pregnancies complicated by preeclampsia with indications of mild
      perinatal asphyxia were included in the study. All were near term. Maternal age
      ranged from 16 to 39 years (mean = 29.05, SD = 6.13). Spectral analysis was used
      to find out any association between respiration and HRV. RESULTS: Respiratory
      sinus arrhythmia (RSA) was reduced in preeclamptic infants with indications of
      mild perinatal asphyxia. This difference was statistically significant (p <
      0.0002, t-test), whereas the heart rate of the two groups was not statistically
      significant (p = 0.1, t-test). CONCLUSION: The results suggest that infants with
      indications of mild preeclampsia differ from controls in respiratory activity and
      this difference is independent of basal heart rate. Thus, spectral analysis could
      be useful for the estimation of influence of mild perinatal asphyxia in the RSA
      rhythm of newborns.

PMID- 11838752
TI  - Breast feeding--when nature fails to satisfy.
AB  - Human milk is the ideal source of nutrition for the healthy neonate. Milk from
      the mother whose diet is sufficient will supply the necessary nutrients. It is a
      considerable problem to discern if the milk supply is the adequate quantity for
      the infant. If the infant's water and caloric needs are not met for several days,
      signs and symptoms of hypernatremic dehydration >10% may develop. This report
      presents a case of a 15-day-old, breast-fed infant who developed significant
      hypernatremic dehydration.

PMID- 11838753
TI  - Supracervical hysterectomy in Trinidad.
AB  - With mounting evidence of the beneficial effects of the retained cervix,
      supracervical hysterectomy is gaining popularity worldwide. In this series of 123
      patients, obesity and pelvic adhesions were the chief factors that prevented
      amputation of the cervix at the time of hysterectomy. We propose that these are
      cogent indications for planned supracervical abdominal hysterectomy in order to
      minimize damage to the adjacent viscera. This option is best justified by a
      risk/benefit analysis.

PMID- 11838754
TI  - Neonatal magnetocardiography.
AB  - PURPOSE: The aim of the present study was to test the validity of
      magnetocardiography (MCG) in the estimation of neonatal cardiac rhythm using a
      single channel superconductive quantum interference device (SQUID). MATERIALS AND
      METHODS: Our study population consisted of 50 neonates who were delivered
      normally between 37-41 weeks of gestation from clinically uncomplicated
      pregnancies. There was also a neonate included in the study in which the
      diagnosis of "hypoplastic left heart syndrome" was demonstrated by U/S Doppler
      examination. Maternal age ranged from 18 to 39 years (mean=29.15, SD=6.13).
      RESULTS: Our study results revealed 44 neonates with normal cardiac rhythm, four
      with ventricular tachycardia (VT), one with ventricular tachycardia (VT) and
      extrasystolic beats and one with bradycardia. The neonate with the hypoplastic
      left heart syndrome presented frequent episodes of ventricular bigeminy in the
      magnetocardiographic trace. M-mode echocardiography confirmed the diagnosis of
      the seven cases of arrhythmia in our study group. CONCLUSION: Results gained from
      the study lead us to believe that MCG could provide clinical practice with a non
      invasive, rapid and easy to perform method, which could be used as an adjunct to
      conventional methods for the evaluation of neonatal cardiac rhythm.

PMID- 11838755
TI  - Spontaneous abortions with increased CD5 positive cells in the placental tissue
      during the first trimester of gestation.
AB  - Most spontaneous abortions occur before 12 weeks' gestation, and most are due to
      chromosomal errors in the conceptus. Relatively few truly spontaneous abortions
      take place between 12 and 20 weeks' gestation. Thereafter, between 20 and 30
      weeks another type of premature spontaneous termination due to ascending
      infection becomes prevalent. The number of cells expressing the various
      lymphocytic markers changes throughout pregnancy. In the present study, we
      investigated the immunohistochemical expression of mononuclear infiltrations in
      paraffin-embedded placentas, from fetuses after spontaneous abortion (8th, 10th,
      and 12th week of gestational age), and those after therapeutic abortion at the
      same time, using a panel of monoclonal antibodies for the identification of
      leukocytes (CD45/LCA), B-lymphocytes (CD20/L-26), T-lymphocytes (CD45RO/UCHL1)
      and CD5 cells. Immunologic factors in human reproductive failure are plausible
      mechanisms of infertility and spontaneous abortion. Approximately 25% of cases of
      premature ovarian failure appear to result from an autoimmune etiology.
      Unfortunately, current therapeutic options for these women are limited to
      exogenous hormone or gamete substitution. Local inflammation at the sites of
      endometriosis implants are postulated to mediate the pain and reduce
      fecundability associated with this clinical syndrome. The recruitment of immune
      cells, particularly monocytes and T cells, neovascularization around foci of
      invading peritoneal lesions, and the possible development of antiendometrial
      autoantibodies support an immunologic basis of this disorder. To date, treatment
      of pain and infertility associated with endometriosis is primarily surgical,
      although immune-based adjuvants are theoretical possibilities for the future.
      Finally, although hypotheses supporting immunologic mechanisms of recurrent
      pregnancy loss have been popular over the past decade, most clinical
      investigations in this area do not provide compelling evidence for this position.
      Reputable specialists in reproductive medicine use experimental immunotherapies
      judiciously in selected cases of repetitive abortion. For example, the use of
      anticoagulation therapy can be beneficial in cases with documented
      antiphospholipid antibodies. At present, however, efficacious immunotherapy
      protocols for general application have not been established. Despite these
      caveats, continued strides in our understanding of human reproductive immunology,
      should yield considerable future progress in this field. We conclude that, 1)
      maternal cells, probably CD45RO/UCHL1 positive cells, cross the maternofetal
      barrier and participate in spontaneous (involuntary) abortions, 2) a small
      proportion of maternal cells (approximately 30%), probably CD5 positive cells,
      also cross the maternal fetal barrier and cause growth delay and recurrent
      reproductive failure. The results were statistically significant (p < 0.0001,
      Student's t-test).

PMID- 11838756
TI  - The value of transvaginal ultrasonography in diagnosis and management of cervical
      incompetence.
AB  - To determine the value of transvaginal sonography in women with a previous
      history of second trimester miscarriage due to cervical incompetence, 55 patients
      were subjected to either elective cervical cerclage or follow-up (every second
      patient) with weekly evaluations of the cervix by transvaginal ultrasonography.
      Emergency cerclage was applied when significant cervical changes were noted. All
      patients were evaluated with cervical cultures and ultrasound. Women with
      infection, fibroids, uterine malformations and multiple pregnancies were excluded
      from the study. The study population was divided in two groups. In group I (n=27)
      elective cerclage was applied during the 14th week. Women in group II (n=28) were
      subjected to serial weekly evaluations of the cervix by transvaginal
      ultrasonograms. In 18 cases emergency cerclage was applied due to significant
      cervical changes. In group I, labor started before the 33rd week in two cases
      (7.4%), between 33 and 37 weeks in nine (33.3%) and after the 37th week in 16
      cases (59.2%). Out of the 18 patients in group II who had cervical cerclage after
      ultrasonographic evaluation, four (22.2%) delivered before the 33rd week, three
      (16.6%) between 33 and 37 weeks and 11 (61.1%) after the 37th week. No
      statistical difference was noted between the two groups referring to pregnancy
      outcome (p<0.1). We concluded that ultrasound-guided management despite cervical
      shortening, does not result in unfavorable pregnancy outcome. A significant
      number of patients can avoid the operation.

PMID- 11838757
TI  - Neonatal magnetoencephalography and spectral analysis.
AB  - PURPOSE: We performed a prospective study of neonatal brain function on 44
      respective term neonates who were delivered normally, without any clinical signs
      of brain damage. Thirty were associated with a normal pregnancy and labor with
      normal values of Apgar scores, umbilical cord pH and birth weight, while 14
      neonates were the result of pre-eclamptic pregnancy. METHODS-RESULTS: Biomagnetic
      measurements were performed by means of a Superconducting Quantum Interference
      Device (SQUID) in an electrically shielded room of low magnetic noise.
      Biomagnetic signals (waveforms) recorded from neonatal brains in the frequency
      range of 2-7 Hz were expressed in terms of magnetic power spectral amplitudes.
      These were low (mean value 163.2, SD 22.57) in almost all neonates from the
      "normal pregnancy" group, while they were high (mean value 211.6, SD 37.74) in
      most neonates from the "pre-eclamptic" group. The difference between the two
      groups was statistically significant (Student's t-test, p < 0.005). CONCLUSION: A
      statistically significant difference in spectral amplitudes of neonatal brain
      activity was observed between normal term neonates and the pre-eclamptic
      neonates. Biomagnetic measurements of neonatal brain activity could provide
      clinical practice with a promising procedure for assessing brain function.

PMID- 11838759
TI  - Doppler ultrasound of the fetomaternal circulation: a preliminary study on
      differences between ethnic groups.
AB  - PURPOSE OF INVESTIGATION: The aim of this study was to investigate whether the
      same reference values might be used for the pulsatility index obtained by Doppler
      examinations of the fetal umbilical and middle cerebral artery and the maternal
      uterine arteries in autochthonous Belgian, Turkish and Moroccan women in Belgium.
      Notching of the uterine artery was also studied in the three ethnic groups.
      METHODS: Doppler measurements were performed in 206 autochthonous Belgian, 36
      Moroccan and 36 Turkish pregnant women between 20 and 24 weeks gestational age
      for the umbilical artery, middle cerebral artery and uterine arteries. The mean
      uterine artery pulsatility index and the placentocerebral index were calculated.
      Intra-observer variation was calculated by repeat measurements on 20 videotaped
      examinations and intrapatient variation was determined by repeat examination in
      60 patients. RESULTS: Maternal length was higher and body mass index lower in
      Belgian women; more of these admitted smoking during pregnancy. There were no
      statistically significant inter-ethnic differences for the pulsatility index of
      the umbilical artery, middle cerebral artery, placental-site uterine artery and
      the placentocerebral index. The pulsatility index in the non-placental-site
      uterine artery and the mean uterine artery was lower in the Moroccan group. Intra
      patient variation expressed as intra-patient standard deviation of the umbilical
      and middle cerebral artery pulsatility index was relatively large compared to
      inter-patient variation, being 57% to 88% of the inter-patient standard
      deviation. This was not the case for the uterine artery. Notching of the uterine
      artery was not contributive for the prediction of intrauterine growth restriction
      or preeclampsia in these ethnic groups. CONCLUSION: Only small statistically
      significant differences were demonstrated. For clinical practice, the use of
      different reference charts for fetomaternal Doppler measurement in Belgian,
      Turkish and Moroccan women is not warranted.

PMID- 11838758
TI  - Cigarette smoking and the degree of maturation of the vaginal squamous epithelium
      in postmenopausal women.
AB  - To determine the effects of cigarette smoking on vaginal squamous epithelium in
      postmenopausal women, we studied the vaginal smear patterns of 199 healthy
      postmenopausal non-smokers and 41 healthy postmenopausal smokers, with a mean age
      of 56 years. A statistically significant difference to the hazard of smokers was
      found in the percentage of smears manifesting absence of maturation of vaginal
      squamous cells. A high incidence of atrophic-type vaginal smears in the group of
      smokers was also found independent of postmenopausal age. In the group of non
      smokers, there was a statistically significant difference between the cytologic
      patterns of smears of women who were in the early postmenopausal age (<10 years)
      and those many years after (> or =10 years). Finally our data suggest that
      smokers had an earlier menopause, on average 2.4 years sooner than non-smokers.
      Cigarette smoking has an effect on vaginal squamous epithelium, but
      pathophysiology still remains unclarified.

PMID- 11838760
TI  - An introduction to microevolution: rate, pattern, process.
AB  - This special issue of Genetica brings together a diverse collection of
      contributions that examine evolution within and among populations (i.e.,
      microevolution), and the role that microevolution plays in the formation of new
      species and morphological forms (i.e., macroevolution). Many of the papers
      present evidence of microevolution occurring over contemporary time frames,
      further validating the near ubiquity of ongoing evolution in the world around us.
      Several synthetic reviews of empirical work help to define the conditions under
      which microevolution is or is not likely to occur. Some of the studies speak
      directly to current controversies in evolutionary biology, such as the relative
      roles of determinism and contingency, and the nature of the relationship between
      microevolution and macroevolution. In general, microevolution seems driven
      largely by deterministic mechanisms, particularly natural selection, but
      contingency plays a role in (1) determining whether or not suitable conditions
      are present for evolution to proceed, and (2) guiding the precise manner by which
      evolution proceeds. Several theoretical treatments and empirical reviews confirm
      previous research in showing that microevolutionary processes are at least
      capable of generating macroevolutionary trends. Macroevolution may indeed reflect
      microevolution writ large but the pattern by which it arises is perhaps best
      characterized as microevolution writ in fits and starts.

PMID- 11838761
TI  - Why the null matters: statistical tests, random walks and evolution.
AB  - A number of statistical tests have been developed to determine what type of
      dynamics underlie observed changes in morphology in evolutionary time series,
      based on the pattern of change within the time series. The theory of the 'scaled
      maximum', the 'log-rate-interval' (LRI) method, and the Hurst exponent all
      operate on the same principle of comparing the maximum change, or rate of change,
      in the observed dataset to the maximum change expected of a random walk. Less
      change in a dataset than expected of a random walk has been interpreted as
      indicating stabilizing selection, while more change implies directional
      selection. The 'runs test' in contrast, operates on the sequencing of steps,
      rather than on excursion. Applications of these tests to computer generated,
      simulated time series of known dynamical form and various levels of additive
      noise indicate that there is a fundamental asymmetry in the rate of type II
      errors of the tests based on excursion: they are all highly sensitive to noise in
      models of directional selection that result in a linear trend within a time
      series, but are largely noise immune in the case of a simple model of stabilizing
      selection. Additionally, the LRI method has a lower sensitivity than originally
      claimed, due to the large range of LRI rates produced by random walks.
      Examination of the published results of these tests show that they have seldom
      produced a conclusion that an observed evolutionary time series was due to
      directional selection, a result which needs closer examination in light of the
      asymmetric response of these tests.

PMID- 11838762
TI  - Rates of evolution on the time scale of the evolutionary process.
AB  - A generational time scale, involving change from one generation to the next, is
      the time scale of evolution by natural selection. Microevolutionary and
      macroevolutionary patterns reflect this process on longer time scales. Rates of
      evolution are most efficiently expressed in haldane units, H, in standard
      deviations per generation, indexed by the log of the time interval. Rates from
      replicated selection experiments and simulations have rate-interval [RI] and log
      rate-log interval [LRI] scaling relations enabling directional, stationary, and
      random time series to be distinguished. Empirical microevolutionary and
      macroevolutionary data exhibit stationary scaling, but point to generational
      rates of evolution (H0) conservatively on the order of 0.2 standard deviations
      per generation on the time scale of the evolutionary process. This paradox of
      long-term stationary scaling and short-term high rates of change can be explained
      by considering the shape of an heuristic time-form evolutionary lattice. Cenozoic
      mammals occupy a lattice that is about four orders of magnitude longer in time
      than it has ever been wide in form. The evolutionary process is dynamic but
      operates within relatively narrow morphological constraints compared to the time
      available for change.

PMID- 11838763
TI  - The pace of modern life II: from rates of contemporary microevolution to pattern
      and process.
AB  - We compiled a database of microevolution on contemporary time scales in nature
      (47 source articles; 30 animal species), comprising 2649 evolutionary rates in
      darwins (proportional change per million years) and 2151 evolutionary rates in
      haldanes (standard deviations per generation). Here we demonstrate how
      quantitative rate measures can provide general insights into patterns and
      processes of evolution. The frequency distribution of evolutionary rates was
      approximately log-normal, with many slow rates and few fast rates. Net selection
      intensities estimated from haldanes were on average lower than selection
      intensities commonly measured directly in natural populations. This difference
      suggests that natural selection could easily accomplish observed microevolution
      but that the intensities of selection typically measured in nature are rarely
      maintained for long (otherwise observed evolutionary rates would be higher).
      Traits closely associated with fitness (life history traits) appear to evolve at
      least as fast as traits less closely tied to fitness (morphology). The magnitude
      of evolutionary difference increased with the length of the time interval,
      particularly when maximum rates from a given study were considered. This pattern
      suggests a general underlying tendency toward increasing evolutionary
      diversification with time. However, evolutionary rates also tended to decrease
      with time, perhaps because longer time intervals average increasingly disparate
      rates over time, or because evolution slows when populations approach new optima
      or as genetic variation is depleted. In combination, our results suggest that
      macroevolutionary transitions may ultimately arise through microevolution
      occasionally 'writ large' but are perhaps temporally characterized by
      microevolution 'writ in fits and starts'.

PMID- 11838764
TI  - Trends and rates of microevolution in plants.
AB  - Evidence for rapid evolutionary change in plants in response to changing
      environmental conditions is widespread in the literature. However, evolutionary
      change in plant populations has not been quantified using a rate metric that
      allows for comparisons between and within studies. One objective of this paper is
      to estimate rates of evolution using data from previously published studies to
      begin a foundation for comparison and to examine trends and rates of
      microevolution in plants. We use data gathered from studies of plant adaptations
      in response to heavy metals, herbicide, pathogens, changes in pH, global change,
      and novel environments. Rates of evolution are estimated in the form of two
      metrics, darwins and haldanes. A second objective is to demonstrate how estimated
      rates could be used to address specific microevolutionary questions. For example,
      we examine how evolutionary rate changes with time, life history correlates of
      evolutionary rates, and whether some types of traits evolve faster than others.
      We also approach the question of how rates can be used to predict patterns of
      evolution under novel selection pressures using two contemporary examples:
      introductions of non-native species to alien environments and global

PMID- 11838765
TI  - The population ecology of contemporary adaptations: what empirical studies reveal
      about the conditions that promote adaptive evolution.
AB  - Under what conditions might organisms be capable of rapid adaptive evolution? We
      reviewed published studies documenting contemporary adaptations in natural
      populations and looked for general patterns in the population ecological causes.
      We found that studies of contemporary adaptation fall into two general settings:
      (1) colonization of new environments that established newly adapted populations,
      and (2) local adaptations within the context of a heterogeneous environments and
      metapopulation structure. Local ecological processes associated with
      colonizations and introductions included exposure to: (1) a novel host or food
      resource; (2) a new biophysical environment; (3) a new predator community; and
      (4) a new coexisting competitor. The new environments that were colonized often
      had depauperate communities, sometimes because of anthropogenic disturbance.
      Local adaptation in heterogeneous environments was also often associated with
      recent anthropogenic changes, such as insecticide and herbicide resistance, or
      industrial melanism. A common feature of many examples is the combination of
      directional selection with at least a short-term opportunity for population
      growth. We suggest that such opportunities for population growth may be a key
      factor that promotes rapid evolution, since directional selection might otherwise
      be expected to cause population decline and create the potential for local
      extinction, which is an ever-present alternative to local adaptation. We also
      address the large discrepancy between the rate of evolution observed in
      contemporary studies and the apparent rate of evolution seen in the fossil
      record.

PMID- 11838766
TI  - Explaining stasis: microevolutionary studies in natural populations.
AB  - Microevolution, defined as a change in the genetic constitution of a population
      over time, is considered to be of commonplace occurrence in nature. Its ubiquity
      can be inferred from the observation that quantitative genetic divergence among
      populations usually exceeds that to be expected due to genetic drift alone, and
      from numerous observations and experiments consistent with local adaptation.
      Experimental manipulations in natural populations have provided evidence that
      rapid evolutionary responses may occur in the wild. However, there are remarkably
      few cases where direct observations of natural populations have revealed
      microevolutionary changes occurring, despite the frequent demonstration of
      additive genetic variation and strong directional selection for particular
      traits. Those few cases where responses congruent with expectation have been
      demonstrated are restricted to changes over one generation. In this article we
      focus on possible explanations as to why heritable traits under apparently strong
      directional selection often fail to show the expected evolutionary response. To
      date, few of these explanations for apparent stasis have been amenable to
      empirical testing. We describe new methods, derived from procedures developed by
      animal breeding scientists, which can be used to address these explanations, and
      illustrate the approach with examples from long-term studies of collared
      flycatchers (Ficedula albicollis) and red deer (Cervus elaphus). Understanding
      why most intensively studied natural populations do not appear to be evolving is
      an important challenge for evolutionary biology.

PMID- 11838767
TI  - Ring species as bridges between microevolution and speciation.
AB  - A demonstration of how small changes can lead to species-level differences is
      provided by ring species, in which two reproductively isolated forms are
      connected by a chain of intermediate populations. We review proposed cases of
      ring species and the insights they provide into speciation. Ring species have
      been viewed both as illustrations of the history of divergence of two species
      from their common ancestor and as demonstrations that speciation can occur in
      spite of gene flow between the diverging forms. Theoretical models predict that
      speciation with gene flow can occur when there is divergent ecological selection,
      and geographical differentiation increases the likelihood of speciation. Thus
      ring species are ideal systems for research into the role of both ecological and
      geographical differentiation in speciation, but few examples have been studied in
      detail. The Greenish warbler is a ring species in which two northward expansions
      around the Tibetan plateau have been accompanied by parallel evolution in
      morphology, ecology, and song length and complexity. However, songs have diverged
      in structure, resulting in a lack of recognition where the reproductively
      isolated forms come into contact in Siberia. Our analysis suggests that these
      differences could have arisen even with gene flow, and that parallel rather than
      divergent ecological changes have led to divergence in sexually selected traits
      and subsequent speciation.

PMID- 11838768
TI  - Microevolution in island rodents.
AB  - We perform a meta-analysis on morphological data from four island rodent
      populations exhibiting microevolution (< approximately/= 100 years). Data
      consisting of incidences of skeletal variants, cranial, and external measurements
      are from house mice (Mus musculus) on one Welsh and one Scottish island, black
      rats (Rattus rattus) on two Galapagos islands, and deer mice (Peromyscus
      maniculatus) on three California Channel islands. We report extremely high rates
      of microevolution for many traits; 60% of all mensural traits measured changed at
      a rate of 600 d or greater (max. 2682 d). The proportion of all mensural traits
      evolving at 600-800 d (23%) was idiosyncratic and departed from an expected
      negative exponential distribution. We argue that selection, rather than founder
      events, is largely responsible for the substantial shifts in morphology seen
      among insular rodents. Examining individual traits, there is a trend towards the
      nose becoming longer and wider, while the skull becomes shallower, shown by both
      rats and mice on five different islands. We found a significant correlation
      between island size and degree of skeletal variant evolution and between island
      distance from the mainland (or nearest island) and degree of cranial and external
      character evolution. Thus, microevolution of rodents is greater on smaller and
      more remote islands.

PMID- 11838769
TI  - Genetic architecture of adaptive differentiation in evolving host races of the
      soapberry bug, Jadera haematoloma.
AB  - To explore genetic architecture and adaptive evolution, we conducted
      environmental and genetic experiments with two recently (ca. 100 generations)
      diverged, geographically adjacent races of the soapberry bug. One race occurs on
      a native host plant species, the other on an introduced host. We focused on three
      traits: length of the mouthparts, body size and development time. The first
      experiment was an environmental manipulation, comparing individuals of each
      population reared on one or the other host species ('cross-rearing') and
      estimating three evolutionary rates for each trait. The first rate, 'evolutionary
      path' compares ancestral-derived populations when both were reared on the
      introduced host. The second, 'current ecological contrast' compares populations
      with each reared on its natal host. The third, 'evolved tradeoff' compares the
      two races when reared on the native host. Differences among these rates are
      striking and informative. For example, development time, which appears to be
      relatively undifferentiated phenotypically, has actually evolved very rapidly via
      countergradient selection. The pattern differs for each trait, and clear
      developmental tradeoffs have evolved as quickly as adaptation to the new host in
      each. The second experiment was a two-generation 'line cross' study. With joint
      scaling analyses, we compared purebred, hybrid and backcrossed individuals to
      describe genetic architecture. Additive genetic variance for mouthpart length was
      consistently large (ca. 60%), but the interaction of dominance, maternal effects
      and epistasis was important in the other traits. Rearing host strongly affected
      genetic architecture. There was no clear relationship between genetic
      architecture and rate of evolution. Selection has produced both additive and
      nonadditive differentiation between the host races with surprising speed,
      consistent with theoretical predictions about evolution in fitness-associated
      traits.

PMID- 11838770
TI  - Rapid evolution of wing size clines in Drosophila subobscura.
AB  - Parallel latitudinal clines across species and continents provide dramatic
      evidence of the efficacy of natural selection, however little is known about the
      dynamics involved in cline formation. For example, several drosophilids and other
      ectotherms increase in body and wing size at higher latitudes. Here we compare
      evolution in an ancestral European and a recently introduced (North America)
      cline in wing size and shape in Drosophila subobscura. We show that clinal
      variation in wing size, spanning more than 15 degrees of latitude, has evolved in
      less than two decades. In females from Europe and North America, the clines are
      statistically indistinguishable however the cline for North American males is
      significantly shallower than that for European males. We document that while
      overall patterns of wing size are similar on two continents, the European cline
      is obtained largely through changing the proximal portion of the wing, whereas
      the North American cline is largely in the distal portion. We use data from sites
      collected in 1986/1988 (Pegueroles et al. 1995) and our 1997 collections to
      compare synchronic (divergence between contemporary populations that share a
      common ancestor) and allochronic (changes over time within a population)
      estimates of the rates of evolution. We find that, for these populations,
      allochronically estimated evolutionary rates within a single population are over
      0.02 haldanes (2800 darwins), a value similar in magnitude to the synchronic
      estimates from the extremes of the cline. This paper represents an expanded
      analysis of data partially presented in Huey et al. (2000).

PMID- 11838772
TI  - High gene flow levels lead to gamete wastage in a desert spider system.
AB  - Field censuses, breeding experiments, and a quantitative model are used to obtain
      insight into the extent and consequences of genetic mixing between locally
      adapted populations of a desert spider. Typically, 9% of the matings of desert
      riparian spiders (non-aggressive phenotype) in native habitat involve an arid
      land partner (aggressive phenotype). Mating was found to be random with respect
      to behavioral phenotype, but linearly related to both the rate of immigration and
      survival of immigrants from surrounding arid habitats in the riparian area.
      Genetic mixing between riparian and arid-land spiders produces offspring that
      exhibit lower rates of survival in riparian habitat. Two extreme behavioral
      phenotypes were also observed in the field studies: approximately 5% of the
      female spiders attacked all males they encountered while another 22% ran from all
      potential mates. Punnett square analyses of the potential genotypes produced by
      introgression between arid- and riparian-adapted spiders indicate that these
      extreme phenotypes appear in F2 generation hybrids and backcrosses. Because there
      is a costly wastage of gametes in the case of mixed phenotype mating, model
      results indicate that within three generations of the cessation of gene flow, the
      riparian population would be free of mixed genotypes and moving towards genetic
      differentiation.

PMID- 11838771
TI  - Insecticide resistance in the mosquito culex pipiens: what have we learned about
      adaptation?
AB  - Resistance to organophosphate (OP) insecticide in the mosquito Culex pipiens has
      been studied for ca. 30 years. This example of micro-evolution has been
      thoroughly investigated as an opportunity to assess precisely both the new
      adapted phenotypes and the associated genetic changes. A notable feature is that
      OP resistance is achieved with few genes, and these genes have generally large
      effects. The molecular events generating such resistance genes are complex (e.g.,
      gene amplification, gene regulation) potentially explaining their low frequency
      of de novo occurrence. In contrast, migration is a frequent event, including
      passive transportation between distant populations. This generates a complex
      interaction between mutations and migration, and promotes competition among
      resistance alleles. When the precise physiological action of each gene product is
      rather well known, it is possible to understand the dominance level or the type
      of epistasis observed. It is however difficult to predict a priori how resistance
      genes will interact, and it is too early to state whether or not this will be
      ever possible. These resistance genes are costly, and the cost is variable among
      them. It is usually believed that the initial fitness cost would gradually
      decrease due to subsequent mutations with a modifier effect. In the present
      example, a particular modifier occurred (a gene duplication) at one resistance
      locus, whereas at the other one reduction of cost is driven by allele replacement
      and apparently not by selection of modifiers.

PMID- 11838773
TI  - Integrating genetic and environmental forces that shape the evolution of
      geographic variation in a marine snail.
AB  - Temporal and spatial patterns of phenotypic variation have traditionally been
      thought to reflect genetic differentiation produced by natural selection.
      Recently, however, there has been growing interest in how natural selection may
      shape the genetics of phenotypic plasticity to produce patterns of geographic
      variation and phenotypic evolution. Because the covariance between genetic and
      environmental influences can modulate the expression of phenotypic variation, a
      complete understanding of geographic variation requires determining whether these
      influences covary in the same (cogradient variation) or in opposing
      (countergradient variation) directions. We focus on marine snails from rocky
      intertidal shores as an ideal system to explore how genetic and plastic
      influences contribute to geographic and historical patterns of phenotypic
      variation. Phenotypic plasticity in response to predator cues, wave action, and
      water temperature appear to exert a strong influence on small and large-scale
      morphological variation in marine snails. In particular, plasticity in snail
      shell thickness: (i) may contribute to phenotypic evolution, (ii) appears to have
      evolved across small and large spatial scales, and (iii) may be driven by life
      history trade-offs tied to architectural constraints imposed by the shell. The
      plasticity exhibited by these snails represents an important adaptive strategy to
      the pronounced heterogeneity of the intertidal zone and undoubtedly has played a
      key role in their evolution.

PMID- 11838774
TI  - Possible consequences of genes of major effect: transient changes in the G
      matrix.
AB  - Understanding the process of evolutionary divergence requires knowledge of the
      strength, form, and targets of selection, as well as the genetic architecture of
      the divergent traits. Quantitative genetic approaches to understanding
      multivariate selection and genetic response to selection have proven to be
      powerful tools in this endeavor, particularly with respect to short-term
      evolution. However, the application of quantitative genetic theory over periods
      of substantial phenotypic change is controversial because it requires that the
      requisite genetic parameters remain constant over the period of time in question.
      We show herein how attempts to determine the stability of key genetic parameters
      may be misled by the 'many genes of small effect' type of genetic architecture
      generally assumed in quantitative genetics. The presence of genes of major effect
      (GOMEs) can alter the genetic variance-covariance matrix dramatically for brief
      periods of time, significantly alter the rate and trajectory of multivariate
      evolution, and thereby mislead attempts to reconstruct or predict long term
      evolution.

PMID- 11838775
TI  - On morphological clocks and paleophylogeography: towards a timescale for Sorex
      hybrid zones.
AB  - Phylogeography--the study of within-species phylogenetic and geographic
      divergence--has been primarily the domain of molecular evolutionists because
      molecular markers record population structure on smaller scales than do
      traditional morphological traits. But when geometric morphometrics are combined
      with distance-based phylogenetics molar shape divergence appears to record
      population-level phylogeny, a fact that allows extant and fossil populations to
      be combined in a single phylogeographic study. The European Sorex araneus complex
      -a genetically complicated group composed of multiple karyotypic races and
      species--illustrates the principle. The phylogeographic patterns revealed by
      molar shape broadly agree with scenarios based on molecular data and
      circumstantial evidence. Importantly, the inclusion of fossil samples of known
      age allows minimum divergence times to be inferred. Some races of S. araneus may
      have diverged more than 120,000 years ago, but others may have diverged less than
      14,000. Supporting evidence that molar shape can be used to reconstruct
      phylogeographic relationships comes from strong correlations between molar shape
      distances and both phylogenetic divergence time and cytochrome b sequence
      divergence in datasets where these variables are known independently (fossil
      carnivorans from a well-constrained stratigraphic setting and shrew species of
      the genus Sorex, respectively). However, molar shape may have a 'saturation
      point' beyond which it is not applicable.

PMID- 11838776
TI  - A population founded by a single pair of individuals: establishment, expansion,
      and evolution.
AB  - Events occurring at the founding of a population, and in the next few
      generations, are potentially of great importance for the future evolution of the
      population. This study reports demographic, genetic, and morphological changes
      that took place during and after the colonization of the small Galapagos island
      of Daphne Major by three male and two female large ground finches, Geospiza
      magnirostris, at the end of 1982. Using assignment tests with microsatellite DNA
      data we demonstrate heterogeneity among the immigrants. Their sources included
      both a near island (Santa Cruz) and a far island (Marchena). However, almost all
      immigrants that stayed to breed were from an intermediate island (Santiago) and
      its satellites. Song may have been responsible for this selectivity. Mean
      heterozygosity stayed roughly constant over the next 15 years while allelic
      diversity almost doubled, after an initial decline, as the breeding population
      increased to a maximum of 30 pairs. Although close inbreeding occurred, with a
      reduction in heterozygosity, an expected net decline in heterozygosity did not
      occur, for two reasons: it was counteracted by continuing gene flow from
      immigrants at a low rate, and inbred birds (in one cohort) were at a selective
      disadvantage. An abrupt step-function shift in beak shape occurred after 9 years.
      Thus the study provides evidence of drift and selection causing morphological and
      genetic divergence in the establishment of a new population and in the first few
      generations.

PMID- 11838777
TI  - Refugial isolation versus ecological gradients. Testing alternative mechanisms of
      evolutionary divergence in four rainforest vertebrates.
AB  - Hypotheses for divergence and speciation in rainforests generally fall into two
      categories: those emphasizing the role of geographic isolation and those
      emphasizing the role of divergent selection along gradients. While a majority of
      studies have attempted to infer mechanisms based on the pattern of species
      richness and congruence of geographic boundaries, relatively few have tried to
      simultaneously test alternative hypotheses for diversification. Here we discuss
      four examples, taken from our work on diversification of tropical rainforest
      vertebrates, in which we examine patterns of genetic and morphological variation
      within and between biogeographic regions to address two alternative hypotheses.
      By estimating morphological divergence between geographically contiguous and
      isolated populations under similar and different ecological conditions, we
      attempt to evaluate the relative roles of geographic isolation and natural
      selection in population divergence. Results suggest that natural selection, even
      in the presence of appreciable gene flow, can result in morphological divergence
      that is greater than that found between populations isolated for millions of
      years and, in some cases, even greater than that found between congeneric, but
      distinct, species. The relatively small phenotypic divergence that occurs among
      long-term geographic isolates in similar habitats suggests that morphological
      divergence via drift may be negligible and/or that selection is acting to produce
      similar phenotypes in populations occupying similar habitats. Our results
      demonstrate that significant phenotypic divergence: (1) is not necessarily
      coupled with divergence in neutral molecular markers; and (2) can occur without
      geographic isolation in the presence of gene flow.

PMID- 11838778
TI  - Experimental studies of adaptive differentiation in Bahamian Anolis lizards.
AB  - Populations of the lizards Anolis carolinensis and A. sagrei were experimentally
      introduced onto small islands in the Bahamas. Less than 15 years after
      introduction, we investigated whether the populations had diverged and, if so,
      whether differentiation was related to island vegetational characteristics or
      propagule size. No effect of founding population size was evident, but
      differentiation of A. sagrei appears to have been adaptive, a direct relationship
      existed between how vegetationally different an experimental island was from the
      source island and how much the experimental population on that island had
      diverged morphologically. Populations of A. carolinensis had also diverged, but
      were too few for quantitative comparisons. A parallel exists between the
      divergence of experimental populations of A. sagrei and the adaptive radiation of
      Anolis lizards in the Greater Antilles; in both cases, relative hindlimb length
      and perch diameter are strongly correlated. This differentiation could have
      resulted from genetic change or environmentally-driven phenotypic plasticity.
      Laboratory studies on A. sagrei from a population in Florida indicate that
      hindlimb length exhibits adaptive phenotypic plasticity. Further studies are
      required to determine if the observed differences among the experimental
      populations are the result of such plasticity. Regardless of whether the
      differences result from plasticity, genetic change, or both, the observation that
      anole populations differentiate rapidly and adaptively when exposed to novel
      environmental conditions has important implications for understanding the
      adaptive radiation of Caribbean anoles.

PMID- 11838779
TI  - Runaway social games, genetic cycles driven by alternative male and female
      strategies, and the origin of morphs.
AB  - Analysis of evolutionarily stable strategies (ESS) and decade-long field studies
      indicate that two color morphs of female side-blotched lizards exhibit density-
      and frequency-dependent strategies. Orange females are r-strategists: they lay
      large clutches of small progeny that are favored at low density. Conversely,
      yellow females are K-strategists: they lay small clutches of large progeny that
      are favored when carrying capacity is exceeded and the population crashes to low
      density. Interactions among three male morphs resembles a rock-paper-scissors
      (RPS) game. Fertilization success of males depends on frequency of neighboring
      morphs. Orange males usurp territory from blue neighbors and thereby mate with
      many females. However, orange males are vulnerable to cuckoldry by sneaky yellow
      males that mimic females. The yellow strategy is thwarted in turn by the mate
      guarding strategy of blue. Sinervo and Lively (1996) developed a simple asexual
      model of the RPS game. Here, we model the dynamics of male and female morphs with
      one- and two-locus genetic models. Male and female games were considered in
      isolation and modeled as games that were genetically coupled by the same locus.
      Parameters for payoff matrices, which describe the force of frequency-dependent
      selection in ESS games, were estimated from free-ranging animals. Period of
      cycles in nature was 5 years for males and 2 years for females. Only the one
      locus model with three alleles (o, b, y) was capable of driving rapid cycles in
      male and female games. Furthermore, the o allele must be dominant to the y allele
      in females. Finally, the amplitude of male cycles was only reproduced in genetic
      models which allowed for irreversible plasticity of by genotypes, which is
      consistent with hormonally-induced changes that transform some males with yellow
      to dark blue. We also critique experimental designs that are necessary to detect
      density- and frequency-dependent selection in nature. Finally, runaway ESS games
      are discussed in the context of self-reinforcing genetic correlations that build
      and promote the formation of morphotypic variation.

PMID- 11838780
TI  - Mechanisms of rapid sympatric speciation by sex reversal and sexual selection in
      cichlid fish.
AB  - Mechanisms of speciation in cichlid fish were investigated by analyzing
      population genetic models of sexual selection on sex-determining genes associated
      with color polymorphisms. The models are based on a combination of laboratory
      experiments and field observations on the ecology, male and female mating
      behavior, and inheritance of sex-determination and color polymorphisms. The
      models explain why sex-reversal genes that change males into females tend to be X
      linked and associated with novel colors, using the hypothesis of restricted
      recombination on the sex chromosomes, as suggested by previous theory on the
      evolution of recombination. The models reveal multiple pathways for rapid
      sympatric speciation through the origin of novel color morphs with strong
      assortative mating that incorporate both sex-reversal and suppressor genes.
      Despite the lack of geographic isolation or ecological differentiation, the new
      species coexists with the ancestral species either temporarily or indefinitely.
      These results may help to explain different patterns and rates of speciation
      among groups of cichlids, in particular the explosive diversification of rock
      dwelling haplochromine cichlids.

PMID- 11838781
TI  - Lateral plate evolution in the threespine stickleback: getting nowhere fast.
AB  - Gasterosteus aculeatus is a small Holarctic fish with marine, anadromous, and
      freshwater populations. Marine and anadromous populations apparently have changed
      little in the past 10 million years and exhibit limited geographical variation.
      In contrast, freshwater isolates have been founded repeatedly by marine and
      anadromous populations, and post-glacial isolates have undergone extraordinary
      adaptive radiation. Stickleback traits that have diversified during post-glacial
      radiation, including the 'lateral plates' (LP), can evolve substantially within
      decades after colonization of fresh water or when the environment (particularly
      predation regime) changes. Although highly divergent freshwater isolates of G.
      aculeatus have existed for at least 10 million years, they have rarely
      experienced sustained evolutionary divergence leading to formation of widespread,
      phenotypically distinct species. The paradox of rapid LP evolution without
      sustained divergence has resulted from selective extinction of highly divergent
      populations, because they are specialized for conditions in small, isolated
      habitats that tend to dry up within limited periods. Biological species of G.
      aculeatus may also evolve within decades, and are also prone to extinction
      because they are endemic to and specialized for small, ephemeral habitats. The
      high rate of evolution observed in contemporary threespine stickleback
      populations may not be unique to this species complex and has important
      implications for use of post-glacial populations in comparative studies,
      speciation rate, and discrimination of sympatric and allopatric speciation.

PMID- 11838782
TI  - Toward a new synthesis: population genetics and evolutionary developmental
      biology.
AB  - Despite the recent synthesis of developmental genetics and evolutionary biology,
      current theories of adaptation are still strictly phenomenological and do not yet
      consider the implications of how phenotypes are constructed from genotypes. Given
      the ubiquity of regulatory genetic pathways in developmental processes, we
      contend that study of the population genetics of these pathways should become a
      major research program. We discuss the role divergence in regulatory
      developmental genetic pathways may play in speciation, focusing on our
      theoretical and computational investigations. We also discuss the population
      genetics of molecular co-option, arguing that mutations of large effect are not
      needed for co-option. We offer a prospectus for future research, arguing for a
      new synthesis of the population genetics of development.

PMID- 11838783
TI  - Sexual conflict and evolution in Trinidadian guppies.
AB  - Recent investigations have highlighted the importance of sexual conflict in the
      evolution of reproductive isolation. Examination of the Trinidadian guppy
      (Poecilia reticulata) shows how geographic variation in sexual conflict can
      mediate the emergence of isolating mechanisms. On the basis of pre-mating
      behaviour guppy females appear to be winning the battle of the sexes in low risk
      localities whereas males are apparently ahead in high-predation environments.
      However, the conclusion that sexual selection (through female choice) is replaced
      by sexual coercion of females (as a consequence of sneaky mating) in predator
      rich (and productive) assemblages takes no account of post-copulatory mechanisms.
      Recent work on sperm competition in guppies suggests coevolution between males
      and females may also occur in the post-mating, pre-zygotic arena. The potential
      for the evolution of reproductive isolation at each stage of the mating sequence
      is assessed.

PMID- 11838784
TI  - A century of life-history evolution in grayling.
AB  - Synchronic and allochronic data sets consisting of phenotypic values of various
      life-history traits from five grayling Thymallus thymallus populations with
      common ancestors were analysed for the purpose of estimating evolution and
      divergence rates. The synchronic data contained both juvenile and adult traits
      from populations that have been segregated for 44-88 years (9-22 generations).
      The allochronic time series contained growth- and maturation data spanning 95
      years (16 generations). Estimated evolution and divergence rates were high
      compared with other life-history studies on the same temporal scale (0.002-1.008
      haldanes, 10-30, 500 darwins). The divergence of adult traits were most probably
      caused by differential mortalities induced by variation in fishing intensity. For
      the population with allochronic data, 48 years (eight generations) of intense and
      consistent size-selective gill-net fishing resulted in a constant reduction in
      age (-0.33 years pr 10 year) and length (-18mm pr 10 year) at maturity. Length-at
      age for ages one to five also decreased during the same period. When gill-net
      fishing was relaxed, age and length at maturity and length-at-age increased.
      Divergence rates for juvenile traits derived from a common-garden experiment were
      high, and standardized selection differentials (s') were high, especially for
      yolk-sac volume (s' = 2.6). We also document that low divergence rates for
      juvenile traits were lower between populations having similar spawning/nursery
      habitats (running water) than populations having relatively different habitats
      (running water v.s. still water). We suggest that the major part of the observed
      phenotypic divergence is mostly due to adaptive evolution, although
      microsatellite data indicate that genetic drift also has occurred.

PMID- 11838785
TI  - Evolution of chinook salmon (Oncorhynchus tshawytscha) populations in New
      Zealand: pattern, rate, and process.
AB  - Chinook salmon, Oncorhynchus tshawytscha, from the Sacramento River, California,
      USA were introduced to New Zealand between 1901 and 1907, and colonized most of
      their present-day range within about 10 years. The New Zealand populations now
      vary in phenotypic traits typically used to differentiate salmon populations
      within their natural range: growth in freshwater and at sea, age at maturity,
      dates of return to fresh water and reproduction, morphology, and reproductive
      allocation. This paper reviews a large research program designed to determine the
      relative contributions of phenotypic plasticity and genetic adaptation to this
      variation, in an effort to understand the processes underlying the natural
      evolution of new populations. We found strong evidence of trait divergence
      between populations within at most 30 generations, particularly in freshwater
      growth rate, date of return, and reproductive output, with plausible adaptive
      bases for these differences. Importantly, we also demonstrated not only a genetic
      basis for post-release survival but higher survival, and hence fitness, of a
      population released from its established site compared to another population
      released from the same site. We conclude that divergence of salmon in different
      rivers probably resulted initially from phenotypic plasticity (e.g., habitat
      specific growth rates, and effects of upriver migration on ovarian investment).
      Philopatry (homing to natal streams) combined with rapid evolution of distinct
      breeding periods to restrict gene flow, facilitating divergence in other traits.
      We also suggest that in addition to genetic divergence resulting from random
      founder effects, divergence may also arise during the very early stages of
      colonization when the original colonists are a non-random, pre-adapted subset of
      the source population. This 'favored founders effect' immediately improves the
      fitness of the new population. Overall, this research reveals the complex
      interplay of environmental and genetic controls over behavior, physiology and
      life history that characterize the early stages of population differentiation, a
      process that has taken place repeatedly during the history of salmon populations.

PMID- 11838786
TI  - Adaptive divergence and the evolution of reproductive isolation in the wild: an
      empirical demonstration using introduced sockeye salmon.
AB  - Populations exposed to different ecological environments should diverge for
      phenotypic traits that influence survival and reproduction. This adaptive
      divergence should reduce gene flow between populations because immigrants become
      less fit than residents and because hybrids perform poorly in either environment
      (i.e., ecologically-dependent reproductive isolation). Here I demonstrate
      adaptive divergence and the evolution of reproductive isolation in populations of
      sockeye salmon (Oncorhynchus nerka) introduced from a common ancestral source
      into a new lake system (Lake Washington, Washington). The introduced fish founded
      several new populations, two of which experience very different environments
      during breeding and early development (Cedar River v.s. Pleasure Point beach).
      Over 13 generations, the two populations diverged for adult traits (female body
      size, male body depth; measured in the wild) and embryo traits (survival to
      hatching, development rate, size at emergence; measured in a common environment).
      The rates of divergence for these characters were similar to those observed in
      other examples of 'rapid evolution', and can best be attributed to natural
      selection. Partial reproductive isolation has evolved in concert with adaptive
      divergence: the rate of exchange of adults between the populations (determined
      using natural tags) is higher than the rate of gene flow (determined using DNA
      microsatellites). The demonstration that adaptive divergence can initiate
      reproductive isolation in less than 13 generations suggests that the first signs
      of 'ecological speciation' may appear soon after new environments are first
      colonized.

PMID- 11838787
TI  - Epistasis, complex traits, and mapping genes.
AB  - Using a three-locus model wherein two loci regulate a third, candidate locus, I
      examine physiological epistasis from the 'gene's eye view' of the regulated
      locus. I show that, depending upon genetic background at the regulatory loci, an
      allele at the candidate locus can be dominant, additive, recessive, neutral, over
      dominant, or under-dominant in its effects on fitness. This kind of variation in
      allelic effect caused by variation in genetic background from population to
      population, from time to time in the same population, or sample to sample makes
      finding and mapping the genes underlying a complex phenotype difficult. The rate
      of evolution of such genes can also be slowed, especially in genetically
      subdivided metapopulations with migration. Nevertheless, understanding how
      variation in genetic background causes variation in allelic effects permits the
      genetic architecture of such complex traits to be dissected into the interacting
      component genes. While some backgrounds diminish allelic effects and make finding
      and mapping genes difficult, other backgrounds enhance allelic effects and
      facilitate gene mapping.

PMID- 11838788
TI  - Population structure inhibits evolutionary diversification under competition for
      resources.
AB  - A model is presented that explores how population structure affects the
      evolutionary outcome of ecological competition for resources. The model assumes
      that competition for resources occurs within groups of a finite number of
      individuals (interaction groups), and that limited dispersal of individuals
      between groups (according to Wright's island model of population structure)
      results in genetic structuring of the population. It is found that both finite
      sized interaction groups and limited dispersal can have substantial effects on
      the evolution of resource exploitation strategies as compared to models with a
      single, infinitely large, well-mixed interaction group. Both effects, in general,
      tend to select for less aggressive competitive strategies. Moreover, both effects
      also tend to reduce the likelihood of the evolutionary diversification of
      resource exploitation strategies that often occurs in models of resource
      competition with infinite populations. The results are discussed in the context
      of theories of the evolutionary diversification of resource exploitation
      strategies and speciation.

PMID- 11838789
TI  - Variation, selection and evolution of function-valued traits.
AB  - We describe an emerging framework for understanding variation, selection and
      evolution of phenotypic traits that are mathematical functions. We use one
      specific empirical example--thermal performance curves (TPCs) for growth rates of
      caterpillars - to demonstrate how models for function-valued traits are natural
      extensions of more familiar, multivariate models for correlated, quantitative
      traits. We emphasize three main points. First, because function-valued traits are
      continuous functions, there are important constraints on their patterns of
      variation that are not captured by multivariate models. Phenotypic and genetic
      variation in function-valued traits can be quantified in terms of variance
      covariance functions and their associated eigenfunctions: we illustrate how these
      are estimated as well as their biological interpretations for TPCs. Second,
      selection on a function-valued trait is itself a function, defined in terms of
      selection gradient functions. For TPCs, the selection gradient describes how the
      relationship between an organism's performance and its fitness varies as a
      function of its temperature. We show how the form of the selection gradient
      function for TPCs relates to the frequency distribution of environmental states
      (caterpillar temperatures) during selection. Third, we can predict evolutionary
      responses of function-valued traits in terms of the genetic variance-covariance
      and the selection gradient functions. We illustrate how non-linear evolutionary
      responses of TPCs may occur even when the mean phenotype and the selection
      gradient are themselves linear functions of temperature. Finally, we discuss some
      of the methodological and empirical challenges for future studies of the
      evolution of function-valued traits.

PMID- 11838790
TI  - The adaptive landscape as a conceptual bridge between micro- and macroevolution.
AB  - An adaptive landscape concept outlined by G.G. Simpson constitutes the major
      conceptual bridge between the fields of micro- and macroevolutionary study.
      Despite some important theoretical extensions since 1944, this conceptual bridge
      has been ignored in many empirical studies. In this article, we review the status
      of theoretical work and emphasize the importance of models for peak movement.
      Although much theoretical work has been devoted to evolution on stationary,
      unchanging landscapes, an important new development is a focus on the evolution
      of the landscape itself. We also sketch an agenda of empirical issues that is
      inspired by theoretical developments.

PMID- 11838791
TI  - The long-term significance of microscopic dural invasion in 354 patients with
      pituitary adenomas treated with transsphenoidal surgery.
AB  - OBJECT: Pituitary adenomas are considered benign tumors; however, they may
      infiltrate surrounding tissues including the dura mater. In this paper the
      authors analyze the clinical significance of microscopically confirmed dural
      invasion by comparing a range of variables (age and sex of patients, adenoma
      type, adenoma size on magnetic resonance [MR] images, remission, residual
      pituitary disease, recurrence, survival, and disease-free interval after surgery)
      between patients with noninvasive adenomas and those with invasive ones. METHODS:
      Between 1992 and 1997 dural specimens were obtained in 354 patients with
      pituitary adenomas who underwent transsphenoidal surgery performed by the senior
      author (E.R.L.). Dural specimens were examined using routine histological methods
      and assessed for invasion by pituitary adenoma tissue. The dura was invaded by
      the pituitary adenoma in 161 patients (45.5%), and in 192 patients (54.5%) no
      evidence of dural invasion was found. Dural invasion was present significantly
      more frequently in the repeated surgery group (69%, 55 patients) than in the
      primary transsphenoidal surgery group (41%, 291 patients). The mean age of
      patients undergoing primary transsphenoidal surgery was significantly older in
      cases of invasive adenomas (50 years) compared with cases of noninvasive adenomas
      (43 years), and these age differences also correlated with adenoma size. Women
      tend to develop clinically evident, smaller adenomas at a younger age than men.
      Of the patients with pituitary adenomas that were 20 mm or smaller, 117 (76%) of
      154 were women, whereas of the patients with adenomas that were larger than 20
      mm, 74 (54%) of 137 were men. The frequency of dural invasion increased with
      increasing size of the pituitary adenoma as measured on MR images. In 291
      patients who underwent primary pituitary surgery, the frequency of dural invasion
      according to adenoma size was 24% (< or = 10 mm), 35% (> 10 to < or = 20 mm), 55%
      (> 20 to < or = 40 mm), and 70% (> 40 mm). In patients who underwent primary
      transsphenoidal surgery, dural invasion was present in more than 50% of those
      with nonfunctioning adenomas and in 30 to 35% of patients with endocrinologically
      active adenomas. The mean diameter of the gonadotrophic adenomas and null-cell
      adenomas was significantly larger than that of each of the endocrinologically
      active adenomas. In 58 (20%) of 291 patients who underwent primary pituitary
      surgery there was residual pituitary disease postsurgery, and 20% of this subset
      of patients showed clinical improvement to such an extent that no further
      management was recommended. After pituitary surgery, residual tumor tissue was
      demonstrable significantly more frequently in patients with invasive adenomas
      than in those with noninvasive adenomas. Recurrences after initial remission
      (cure) of pituitary disease occurred in 18 (8.8%) of 205 patients between 2 and
      79 months after primary pituitary surgery (median 25 months). The recurrence rate
      was not related to dural invasion in a consistent or significant fashion. Seven
      patients died between 14 and 79 months after pituitary surgery and all had
      invasive adenomas identified on gross observation at surgery and on microscopy.
      The survival rate was slightly but significantly decreased for patients with
      invasive adenomas (91%) compared with patients with noninvasive adenomas (100%)
      at 6 years postsurgery. CONCLUSIONS: The principal significance of dural invasion
      by pituitary adenoma is the persistence of tumor tissue after transsphenoidal
      surgery (incomplete adenomectomy; 20% in primary pituitary tumor resections). The
      increase in adenoma size with time and the concurrent development of dural
      invasion are the major factors that determine an incomplete adenomectomy. When
      the adenoma remains restricted to the sellar compartment or shows only moderate
      suprasellar extension, dural invasion may not yet have developed and conditions
      for complete selective adenomectomy are improved.

PMID- 11838792
TI  - Changes in the epithelium of Rathke cleft cyst associated with inflammation.
AB  - OBJECT: Rathke cleft cysts (RCCs) are composed of tall, well-differentiated,
      ciliated columnar epithelia. Their structures are altered by hyperplasia or
      squamous metaplasia, but their cause remains unknown. METHODS: The authors
      studied pathological findings and anterior pituitary function in 20 patients
      harboring RCCs. They classified RCC epithelium as either single (a single
      ciliated columnar cell lining or a flattened cuboidal cell lining) or stratified
      (a stratified ciliated columnar cell lining, basal cell hyperplasia, columnar
      cell hyperplasia, or squamous metaplasia). Inflammation was classified as acute,
      subacute, chronic, or end stage. The epithelial cell lining was observed in 13
      specimens obtained during surgery (six specimens contained single and seven
      contained stratified epithelia). Inflammation had penetrated the cyst epithelium
      or subjacent stroma in 10 patients, and the stage of inflammation correlated well
      with the type of epithelia group: early stages of inflammation in the single
      epithelium group and chronic or end-stage inflammation in the stratified
      epithelia (p = 0.0027). The adenohypophysis was identified in 21 surgical
      specimens. Postoperatively, growth hormone (p = 0.019), cortisol (p = 0.027), and
      thyroid-stimulating hormone (p = 0.039) responses significantly worsened as the
      inflammation progressed. The presence of diabetes insipidus correlated well with
      advanced stages of neurohypophysitis (p = 0.025). CONCLUSIONS: Epithelial
      stratification in the RCC is caused by inflammation that may extend into the
      adjacent adenohypophysis or neurohypophysis and overwhelm the hypophysis,
      resulting in panhypopituitarism. Transsphenoidal excision may represent the best
      choice for treatment, at least for cases of RCC in which there is partial
      impairment of hypophysial function.

PMID- 11838793
TI  - Predictors of vestibular schwannoma growth in patients with neurofibromatosis
      Type 2.
AB  - OBJECT: The results of two longitudinal studies of growth rates of vestibular
      schwannomas (VSs) in patients with neurofibromatosis Type 2 (NF2) differ as to
      whether VS growth rates decrease or increase with increasing patient age. The
      authors undertook this study to assess the relationship between VS growth rates
      and patient age and type of constitutional NF2 mutation; they also examined
      variability in VS growth rates among multiple patients in families with NF2.
      METHODS: Gadolinium-enhanced magnetic resonance images obtained in 18 patients
      with inherited NF2 from 11 unrelated families were retrospectively analyzed. The
      patients had been observed for a median of 4 years. Volumes of the VSs were
      measured using a two-component box model (intrameatal and extrameatal parts
      measured separately). Single-strand conformation polymorphism analysis and
      Southern blot analysis were used to identify constitutional NF2 mutations. Growth
      rates of the VSs were highly variable, but tended to decrease with increasing
      patient age both at onset of signs or symptoms of NF2 (r2 = 0.35, p = 0.026) and
      at diagnosis (r2 = 0.33, p = 0.012). The VS growth rates did not vary
      significantly with the type of constitutional NF2 mutation or the number of non
      VS cerebral or spinal tumors. The VS growth rates were highly variable within
      families and did not correspond to clinical indices of NF2 disease severity, such
      as patient age at symptom onset and the number of non-VS cerebral and spinal
      tumors. CONCLUSIONS: The growth rates of VSs in patients with NF2 are highly
      variable, but tend to decrease with increasing patient age. Clinical treatment of
      multiple patients in families with NF2 cannot be based on the expectations of
      similar VS growth rates, even when other clinical aspects of disease severity are
      similar.

PMID- 11838794
TI  - Vestibular schwannoma growth in patients with neurofibromatosis Type 2: a
      longitudinal study.
AB  - OBJECT: The factors that determine the growth rates of vestibular schwannomas
      (VSs) in patients with neurofibromatosis Type 2 (NF2) are unknown. The authors
      undertook this study to determine if clinical factors or type of constitutional
      NF2 mutation were associated with VS growth rates in cases of NF2. METHODS: The
      authors reviewed serial gadolinium-enhanced magnetic resonance (MR) images of the
      head and full spine of 37 patients with sporadic NF2 who had been observed over
      periods ranging from 0.2 to 8 years (median 3.9 years) at a specialized referral
      clinic for NF2. A box model was used to calculate VS volumes so that tumor growth
      rates could be estimated. Temperature-gradient gel electrophoresis was used to
      screen for constitutional NF2 mutations. The VS growth rates tended to decrease
      with increasing patient age at onset of signs or symptoms (r2 = 0.23, p = 0.003)
      and at the time the baseline gadolinium-enhanced MR image was obtained (r2 =
      0.38, p < 0.001). The authors did not find significant associations between VS
      growth rates and the number of non-VS cerebral or spinal tumors or different
      types of constitutional NF2 mutations. CONCLUSIONS: There is considerable
      variability in growth rates of VSs in patients with NF2, but they tend to be
      higher in patients who are younger at onset of signs or symptoms.

PMID- 11838795
TI  - Quality-of-life assessment in patients who had been surgically treated for
      cerebellar pilocytic astrocytoma in childhood.
AB  - OBJECT: After radical surgery for childhood cerebellar astrocytomas, patients are
      considered to be cured. Long-term follow up demonstrates that these patients
      survive, with most of them leading a normal life. The study reported here was
      aimed at assessing the quality of life (QOL) of these adults, which is defined as
      a person's sense of well-being, as derived from his or her current experience of
      life as a whole. METHODS: Twenty patients who had undergone surgery between 1970
      and 1985 were enrolled in the study. In four patients ventriculoperitoneal shunts
      were in place; two of these patients had required more than six shunt revisions.
      At present, all patients have clear neuroimaging studies and their Karnofsky
      Performance Scale (KPS) scores are as follows: 70 in three, 80 in seven, 90 in
      six, and 100 in four. A QOL questionnaire was administered to the patients and to
      a control group consisting of 20 healthy volunteers of matching age and sex. The
      chi-square test was applied to compare patients and controls. Traditional
      questions on the level of education, work, whether the patients have their own
      families, and whether they possessed a driver's license were asked at the end of
      the questionnaire. In all the dimensions assessed except one (sex life), the
      difference between patients and control volunteers was significant, socializing
      and adolescence being the most striking ones. This was also true when the three
      patients with the lowest KPS scores and the worst QOL results were excluded.
      CONCLUSIONS: By traditional standards, these patients appear to fare quite well.
      Nevertheless, their self-reported life experience is unsatisfying when compared
      with the control group. The authors conclude that psychosocial factors are
      critical to complete recovery and the QOL of children who undergo successful
      operations for benign cerebellar astrocytoma.

PMID- 11838796
TI  - Pterional surgery of meningiomas of the tuberculum sellae and planum sphenoidale:
      surgical results with special consideration of ophthalmological and
      endocrinological outcomes.
AB  - OBJECT: The authors reviewed 47 cases of suprasellar meningiomas with special
      attention to ophthalmological and endocrinological outcomes. METHODS: All
      patients underwent surgery performed via a unilateral pterional approach between
      January 1983 and January 1998. Ophthalmological and endocrinological examinations
      were performed before the operation as well as 1 week and 3 months
      postoperatively. A special scoring system was adopted to quantify the extent of
      ophthalmological disturbances. Complete tumor resection was possible in all but
      one patient. There were no fatalities and the rate of visual improvement was 80%.
      The best prognoses were found in patients younger than 50 years and in patients
      in whom the duration of symptoms was less than 1 year. Before surgery, tumor
      related endocrine disturbances were present in only three women who suffered from
      secondary hypogonadism; two of these patients recovered after surgery.
      Postoperatively, no patient needed replacement therapy for pituitary dysfunction.
      The overall tumor recurrence rate was 2.1% (one of 47 cases). For patients in
      whom long-term (> 5 years) follow-up data were available, the recurrence rate was
      4.2% (one of 24 cases). CONCLUSIONS: In this series, complete resection of
      suprasellar meningiomas was possible through a unilateral pterional craniotomy
      and was associated with a low morbidity rate and no deaths.

PMID- 11838797
TI  - Titanium miniplates or stainless steel wire for cranial fixation: a prospective
      randomized comparison.
AB  - OBJECT: The authors designed a study to compare low-profile titanium miniplate
      fixation to that in which stainless steel wire is used. METHODS: Before
      undergoing craniotomy, 40 patients gave informed consent and were randomized to
      receive either wire or miniplate fixation. After dural closure, bone flap
      fixation was timed. The bone flap was measured for inward or outward offset and
      mobility to manual pressure on its margin. Three months postoperatively the bone
      flap margins were graded for appearance or palpation of an offset and for the
      presence of burr hole depressions. Twenty-four patients were randomized to
      receive miniplate fixation and 16 to receive stainless steel wire fixation. The
      time required for wire fixation was approximately 40% longer than that for
      miniplates (11.8 +/- 5.1 minutes compared with 8.3 +/- 5 minutes, p = 0.02). The
      offset of bone flaps after wire fixation was significantly greater than that with
      miniplates (1.6 +/- 1 mm compared with 0.3 +/- 0.6 mm, p < 0.001), as was the
      mobility of the bone flap on digital pressure (1.2 +/- 0.9 mm compared with 0.2
      +/- 0.5 mm, p < 0.001). At the 3-month follow-up review, two of 12 patients had
      suboptimal results after wire fixation, whereas none of 14 patients had
      suboptimal results after miniplate fixation. When dichotomized for excellent or
      less-than-excellent postoperative results, the data were significantly better for
      patients who underwent miniplate fixation (p < 0.05). CONCLUSIONS: Titanium
      miniplate cranial fixation provides more accurate and rigid reapproximation of
      the bone edges, with results that are significantly better on close inspection or
      palpation. The additional cost of miniplate fixation may thus be justified in
      many cases.

PMID- 11838798
TI  - Cerebellar hemorrhage arising postoperatively as a complication of supratentorial
      surgery: a retrospective study.
AB  - OBJECT: Postoperative cerebellar hemorrhage as a complication of supratentorial
      surgery is an increasingly recognized clinical entity. So far, it has remained
      unclear whether this complication constitutes an intraoperative or postoperative
      event. The observation of such cases prompted the authors to analyze
      retrospectively their series of supratentorial craniotomies. The aim of this
      study was to determine the incidence of cerebellar hemorrhage and its temporal
      relationship to supratentorial surgery. METHODS: The authors reviewed discharge
      notes and reports on postoperative computerized tomography (CT) scans for 1650
      patients who had undergone supratentorial craniotomy between January 1998 and
      February 2001. The retrospective study led to the identification of 10 patients
      who had sustained cerebellar hemorrhage as a complication of supratentorial
      surgery. Because it was routine to perform CT scanning following craniotomy, an
      early CT scan obtained within the 1st postoperative hour (mean 24 minutes after
      wound closure) was available in eight of the 10 patients. In seven of these
      patients no hemorrhage was found immediately after surgery, and in only one
      patient was there the suspicion of cerebellar hemorrhage. In the whole series of
      10 patients, cerebellar hemorrhage was detected during the later postoperative
      course, after a mean interval of 7 hours and 35 minutes (range 1 hour and 49
      minutes-144 hours) following surgery. The incidence of cerebellar hemorrhage was
      0.6% of all patients who underwent supratentorial surgery. Among patients
      suffering from epilepsy the incidence was 4.6%, and in those patients who
      underwent temporal lobe resection it was 12.9%. CONCLUSIONS: The authors have
      demonstrated that cerebellar hemorrhage as a complication of supratentorial
      surgery arises not as an intraoperative event, but as a postoperative event.
      Resective nontumorous temporal lobe procedures place patients at particular risk
      for this complication. Evidence suggests that the complication might be
      precipitated by postoperative suction drainage.

PMID- 11838799
TI  - The impact of neurophysiological intraoperative monitoring on surgical decisions:
      a critical analysis of 423 cases.
AB  - OBJECT: The aim of this observational clinical study was to analyze the impact of
      neurophysiological intraoperative monitoring (IOM) on the surgical procedure and
      to assess the benefits of such monitoring. METHODS: Data for 423 patients who
      underwent neurophysiological IOM with somatosensory evoked potentials and
      brainstem auditory evoked potentials during neurosurgical procedures were
      collected prospectively. The patients were classified into one of five groups
      according to the findings of IOM, the intervention following a monitoring alarm,
      and the patient's postoperative neurological condition. These groups were as
      follows: patients with true-positive findings with intervention (42 cases, 9.9%),
      those with true-positive findings without intervention (42 cases, 9.9%), those
      with false-positive findings (nine cases, 2.1%), those with false-negative
      findings (16 cases, 3.8%), and those with true-negative findings (314 cases,
      74.2%). Different interventions followed an event identified with monitoring.
      These interventions were related to dissection in 17 cases, to perfusion pressure
      in 11, to a limitation of the surgical procedure in five, to vessel clipping in
      four, to vasospasm in three, and to retraction in one case. In one case the
      surgical procedure was abandoned. A critical analysis and cautious estimation of
      the interventions revealed that IOM was helpful in preventing a postoperative
      deficit in 5.2% of the monitored cases. CONCLUSIONS; For critical analysis of the
      benefits of IOM one must evaluate not only the findings of IOM and the patient's
      postoperative neurological condition but also the intraoperative findings and
      surgical interventions following a monitoring alarm. Evidence is presented that
      IOM is helpful in preventing a postoperative deficit.

PMID- 11838801
TI  - Bilateral high-frequency stimulation in the subthalamic nucleus for the treatment
      of Parkinson disease: correlation of therapeutic effect with anatomical electrode
      position.
AB  - OBJECT: The goal of this study was to relate the degree of clinical improvement
      and that of energy consumption to the anatomical position of electrode poles used
      for long-term stimulation. METHODS: The authors conducted a retrospective
      analysis of 15 consecutive patients in whom targeting of the subthalamic nucleus
      (STN) had been performed using ventriculography, three-dimensional (3D) magnetic
      resonance (MR) imaging, and 3D computerized tomography, together with
      macrostimulation and teleradiographic control of the electrode position. In these
      patients the follow-up period ranged from 6 to 12 months. Postoperative
      improvement in contralateral motor symptoms, which was assessed by assigning a
      lateralized motor subscore of the Unified Parkinson's Disease Rating Scale
      (UPDRS), and stimulus intensity required for optimal treatment results were
      correlated with the intracerebral position of the active electrode pole.
      Bilateral high-frequency stimulation of the STN improved the UPDRS motor score
      during the medication-off period by an average of 60.5% compared with that at
      baseline. Repeated transfer of stereotactic coordinates from postoperative
      teleradiography to treatment-planning MR images documented the proper
      localization of the most distal electrode pole (pole 0) in the targeted STN.
      Nevertheless, in most cases the best clinical improvement was achieved using
      electrode poles that were located several millimeters above the electrode tip. If
      the relative improvement in motor symptoms was correlated with the required
      electrical energy for chronic stimulation, the best coefficient was observed for
      active electrode poles projecting onto white matter dorsal to the STN.
      CONCLUSIONS: This observation makes blocking or activation of large fiber
      connections arising in the STN or running nearby more likely than electrical
      interference with cell bodies inside the STN. Anatomical correlates may be the
      pallidothalamic bundle (including Field H of Forel and the thalamic fascicle),
      the pallidosubthalamic tract, and/or the zona incerta.

PMID- 11838800
TI  - Measurement of brain tissue oxygenation performed using positron emission
      tomography scanning to validate a novel monitoring method.
AB  - OBJECT: The benefits of measuring cerebral oxygenation in patients with brain
      injury are well accepted; however, jugular bulb oximetry, which is currently the
      most popular monitoring technique used has several shortcomings. The goal of this
      study was to validate the use of a new multiparameter sensor that measures brain
      tissue oxygenation and metabolism (Neurotrend) by comparing it with positron
      emission tomography (PET) scanning. METHODS: A Neurotrend sensor was inserted
      into the frontal region of the brain in 19 patients admitted to the
      neurointensive care unit. After a period of stabilization, the patients were
      transferred to the PET scanner suite where C15O, 15O2, and H2(15)O PET scans were
      obtained to facilitate calculation of regional cerebral blood volume, O2
      metabolism, blood flow, and O2 extraction fraction (OEF). Patients were given
      hyperventilation therapy to decrease arterial CO2 by approximately 1 kPa (7.5 mm
      Hg) and the same sequence of PET scans was repeated. For each scanning sequence,
      end-capillary O2 tension (PvO2) was calculated from the OEF and compared with the
      reading of brain tissue O2 pressure (PbO2) provided by the sensor. In three
      patients the sensor was inserted into areas of contusion and these patients were
      eliminated from the analysis. In the subset of 16 patients in whom the sensor was
      placed in healthy brain, no correlation was found between the absolute values of
      PbO2 and PvO2 (r = 0.2, p = 0.29); however a significant correlation was obtained
      between the change in PbO2 (deltaPbO2) and the change in PvO2 (deltaPvO2)
      produced by hyperventilation in a 20-mm region of interest around the sensor (p =
      0.78, p = 0.0035). CONCLUSIONS: The lack of correlation between the absolute
      values of PbO2 and PvO2 indicates that PbO2 cannot be used as a substitute for
      PvO2. Nevertheless, the positive correlation between deltaPbO2 and deltaPvO2 when
      the sensor had been inserted into healthy brain suggests that tissue PO2
      monitoring may provide a useful tool to assess the effect of therapeutic
      interventions in brain injury.

PMID- 11838802
TI  - Evaluation of the healing process after dural reconstruction achieved using a
      free fascial graft.
AB  - OBJECT: This study was undertaken to investigate the healing process and to
      delineate factors important for the survival of free fascial grafts used for
      dural repair. METHODS: A dural defect was created in guinea pigs and then
      reconstructed using either a free fascial graft or an expanded
      polytetrafluoroethylene (ePTFE) sheet. The fascial graft was covered directly by
      subcutaneous tissue (Group I) or by a silicone sheet to prevent tissue ingrowth
      from the subcutaneous tissue (Group II). The ePTFE sheet was covered with a
      silicone sheet (Group III). One or 2 weeks postoperatively, the strength of the
      dural repair was evaluated by determining the pressure at which cerebrospinal
      fluid (CSF) leaked through the wound margins. The dural repair was also
      histologically examined. In addition, using a rat model, specimens obtained from
      similar reconstruction sites were immunohistochemically stained with antibodies
      against basic fibroblast growth factor (bFGF), epidermal growth factor, or
      transforming growth factor-beta. The pressures at which CSF leaked after 1 and 2
      weeks, respectively, were 50 +/- 14 mm Hg and 126 +/- 20 mm Hg in Group I, 70 +/-
      16 mm Hg and 101 +/- 38 mm Hg in Group II, and 0 mm Hg and 8 +/- 8 mm Hg in Group
      III. Failure of repairs made in Group III occurred at significantly lower
      pressures when compared with Groups I and II. In Groups I and II, a thick fibrous
      tissue formed around the fascial graft. This tissue tightly adhered to adjacent
      dura mater. The fibrous tissue displayed a positive reaction for the presence of
      bFGF. In Group III, only a thin fibrous membrane surrounded the ePTFE sheet.
      CONCLUSIONS: Fascial grafts tolerated extraordinary intracranial pressures at 1
      week postoperatively. Free fascial grafts can heal with durable fibrous tissue
      without the presence of a blood supply from an overlying vascularized flap.

PMID- 11838804
TI  - Association of elevated glial expression of interleukin-1beta with improved
      survival in patients with glioblastomas multiforme.
AB  - OBJECT: The aim of this study was to investigate the association of interleukin
      1beta (IL-1beta) expression with improved survival in patients with glioblastomas
      multiforme (GBMs). Immune and vascular host-tumor interactions play a pivotal
      role in the control of tumor development, and inflammatory mechanisms may
      participate in the host's defense against tumor cells. Expression of
      proinflammatory cytokines and of inducible nitric oxide synthase (iNOS) has been
      noted in various types of malignant tumors, raising the possibility that
      endogenous expression of cytokines and the resulting cytotoxic action of
      sustained NO production play a role in the control of tumor growth. Indeed, human
      GBMs express variable amounts of iNOS. METHODS: In this study, the expression of
      iNOS and of cytokines known to upregulate IL-1beta, tumor necrosis factor-alpha,
      interferon-gamma or downregulate iNOS transcription (IL-10, transforming growth
      factor [TGF]beta1, and TGFbeta2) were measured using reverse transcription
      polymerase chain reaction with competitor DNA in 39 samples of human GBM. The
      iNOS level in GBM was positively correlated with IL-1beta messenger (m)RNA, but
      not with the other cytokines tested. Immunocytochemical double labeling revealed
      that both anti-iNOS immunoreactivity and anti-IL-1beta immunoreactivity
      colocalized with glial fibrillary acidic protein immunoreactivity in GBM. Some
      macrophage/microglial cells also expressed iNOS, but not IL-1beta. Comparison of
      biological data with clinical parameters indicated that the survival duration was
      enhanced when levels of IL-1beta mRNA were elevated or when levels of TGFbeta2
      were low, but was independent of the level of iNOS mRNA within the tumor.
      CONCLUSIONS: Taken together, these data indicate that the proinflammatory
      cytokine IL-1beta produced within GBM by glial-derived cells has a negative
      impact on tumor growth through a mechanism independent of iNOS induction.

PMID- 11838803
TI  - Brain edema after experimental intracerebral hemorrhage: role of hemoglobin
      degradation products.
AB  - OBJECT: The mechanisms involved in brain edema formation following intracerebral
      hemorrhage (ICH) have not been fully elucidated. The authors have found that red
      blood cell lysis plays an important role in edema development after ICH. In the
      present study, they sought to determine whether degradation products of
      hemoglobin cause brain edema. METHODS: Hemoglobin, hemin, bilirubin, or FeCl2
      were infused with stereotactic guidance into the right basal ganglia of Sprague
      Dawley rats. The animals were killed 24 hours later to determine brain water and
      ion contents. Western blot analysis and immunohistochemistry were applied for
      heme oxygenase-1 (HO-1) measurement. The effects of an HO inhibitor, tin
      protoporphyrin (SnPP), and the iron chelator deferoxamine, on hemoglobin-induced
      brain edema were also examined. Intracerebral infusion of hemoglobin, hemin,
      bilirubin, or FeCl2 caused an increase in brain water content at 24 hours. The HO
      1 was upregulated after hemoglobin infusion and HO inhibition by SnPP-attenuated
      hemoglobin-induced edema. Brain edema induced by hemoglobin was also attenuated
      by the intraperitoneal injection of 500 mg/kg deferoxamine. CONCLUSIONS:
      Hemoglobin causes brain edema, at least in part, through its degradation
      products. Limiting hemoglobin degradation coupled with the use of iron chelators
      may be a novel therapeutic approach to limit brain edema after ICH.

PMID- 11838805
TI  - Prereperfusion flushing of ischemic territory: a therapeutic study in which
      histological and behavioral assessments were used to measure ischemia-reperfusion
      injury in rats with stroke.
AB  - OBJECT: In ischemic stroke, the ischemic crisis activates a cascade of traumatic
      events that are potentiated by reperfusion and eventually lead to neuronal
      degeneration. The primary aim of this study was to investigate a procedure that
      could minimize this damage by interfering with the interactions between
      reestablished blood flow and ischemically damaged tissue, as well as by improving
      regional microcirculation. METHODS: Using a novel hollow filament, the authors
      flushed the ischemic territory with heparinized saline before vascular
      reperfusion after occlusion of the middle cerebral artery (MCA). The results
      demonstrate a statistically significant (p < 0.001) reduction in infarct volume
      (75%; from 45.3 +/- 3.6% to 11.4 +/- 1.7%, determined with Nissl staining) in
      rats in which a 2-hour MCA occlusion was followed by a 48-hour reperfusion.
      Infarction and neuronal degeneration were confirmed using silver staining, which
      revealed a significantly larger infarct (36.3%, p < 0.05) than that detected with
      Nissl staining. The long-term neuroprotection of the prereperfusion flushing was
      also evaluated. This was determined by a series of motor behavior tasks (foot
      placing, parallel bar traversing, rope and ladder climbing) performed up to 28
      days after reperfusion. Motor deficits were found to be significantly ameliorated
      in animals that underwent the flushing procedure (p < 0.001). In addition,
      neurological outcome was also improved significantly (p < 0.001) in the same
      animals. CONCLUSIONS: These results indicate that interaction between reperfusion
      and the metabolically and biochemically compromised tissue could be interrupted
      by the prereperfusion flushing procedure, which could lead to a reduction in
      brain injury from stroke. Mechanical reopening of the cerebral occlusion with
      local flushing and isolated reperfusion of the regionally injured brain might
      offer new treatment options for patients with stroke.

PMID- 11838806
TI  - Superficial surgical landmarks for the frontal sinus.
AB  - OBJECT: There is a lack of reports in the literature that contain descriptions of
      superficial anatomical landmarks for the identification of the internally located
      frontal sinus. Neurosurgeons must often enter the cranium through the frontal
      bone and knowledge of the frontal sinus is essential to minimize complications.
      METHODS: Seventy adult cadaveric frontal sinuses were evaluated. Measurements
      included both the lateral and superior extent of the frontal sinus in reference
      to a midpupillary line, and the superior extent of the frontal sinus from the
      nasion. Frontal sinuses were found bilaterally in all specimens. The mean height
      of the frontal sinus superior to the nasion was 2.8 cm. In 71.4% and 74.3% of
      specimens the lateral extent of the frontal sinus was found to be medial to the
      left and right midpupillary line, respectively. Distances superior to a plane
      drawn through the supraorbital ridges at a midpupillary line included a mean of
      2.5 mm for the left side and 1.8 mm for the right side. CONCLUSIONS: Of 70
      sinuses, none extended more than 5 mm lateral to a midpupillary line. At this
      same midpupillary line and at a plane drawn through the supraorbital ridges, the
      frontal sinus was never higher than 12 mm. Finally, in the midline the frontal
      sinus never reached more than 4 cm above the nasion. These measurements will
      assist surgeons who must manipulate the frontal bone.

PMID- 11838807
TI  - Accuracy of transcranial color Doppler ultrasonography in the diagnosis of middle
      cerebral artery spasm determined by receiver operating characteristic analysis.
AB  - OBJECT: The value of transcranial Doppler ultrasonography for the detection of
      middle cerebral artery (MCA) spasm has been asserted. None of the published
      studies, however, has adequately scrutinized the overall diagnostic accuracy of
      this procedure. There are only sporadic reports concerning the utility of
      transcranial color Doppler (TCCD) ultrasonography, although this method has been
      proved to be more precise. In this study the authors attempted to estimate the
      performance of TCCD ultrasonography in detecting MCA narrowing by using receiver
      operating characteristic (ROC) curve analysis, based on TCCD studies obtained in
      a relatively large, randomly selected population of patients. METHODS:
      Transcranial color Doppler ultrasonography studies were obtained in 100
      consecutive patients (54 men and 46 women ages 18-74 years, median age 50 years)
      routinely referred by neurosurgeons for intraarterial angiography. The M1 segment
      of the MCA was insonated using a 2.5-MHz probe via a temporal acoustic window,
      and angle-corrected flow velocities were obtained. Angiographically depicted
      vasospasm was graded as none, mild (< or = 25% vessel caliber reduction), and
      moderate to severe (> 25% vessel caliber reduction). The effectiveness of TCCD
      ultrasonography in diagnosing MCA spasm was evaluated by calculating the areas
      under the ROC curves (Az). Of the 200 MCAs examined, 173 were successfully
      visualized with the aid of TCCD ultrasonography. Mild vasospasm was
      angiographically diagnosed in 15 arteries and moderate-to-severe vasospasm in 28.
      The best-performing TCCD parameter for the detection of MCA narrowing was
      revealed to be peak systolic velocity. The Az value for moderate-to-severe
      vasospasm only was 0.93 and that for all vasospasms was 0.8. The best efficiency,
      that is, the optimal tradeoff between sensitivity and specificity in diagnosing
      vasospasms, was associated with a peak systolic velocity of 182 cm/second.
      CONCLUSIONS: The performance of TCCD ultrasonography in the diagnosis of advanced
      MCA narrowing is very good, and is acceptable for all vasospasms. The best
      performing parameter was peak systolic velocity.

PMID- 11838808
TI  - Electromagnetic field hazards involving adjustable shunt valves in hydrocephalus.
AB  - OBJECT: Standard therapy for hydrocephalus involves shunts and valves, which are
      frequently adjustable. Because of increasing "electromagnetic smog" (for example,
      that generated by cellular phones), these valves are often exposed to
      electromagnetic fields. METHODS: Various magnetic fields were tested for their
      effects on two different kinds of adjustable valves. The minimum magnetic flux
      density affecting the adjustment of the valve was determined. Results were
      compared with magnetic fields found in contemporary everyday life. In homogeneous
      magnetic fields the adjustment of one valve (Sophysa model SM8) was changed at 5
      mT, whereas the second valve (Codman Hakim model CM) was not affected. In
      nonhomogeneous fields the SM8 valve was affected at 25 mT and the CM valve at 15
      mT. Thus, these valves may be affected by headphones and telephone receivers.
      Surroundings such as the Japanese magnetic suspension railway and the lead cabin
      of electrical railway engines, in which critical levels of magnetic flux may be
      present, may also affect adjustable valves. The high-frequency fields of cellular
      phones, however, have no effect on these valves. CONCLUSIONS: Every surgeon who
      implants these valves and every patient who receives them should know the
      possible hazards. The valve selection should be adapted to the environment of the
      patient. Devices with critical levels of electromagnetic flux that are used in
      the homes of patients should be replaced by ones with lower magnetic fields. The
      future construction of these valves should be modified in such a way that their
      adjustment requires a higher magnetic flux density, so that the valves become
      less sensitive to unwanted effects from environmental magnetic fields.

PMID- 11838809
TI  - Preclinical evaluation of a novel device for delivering brachytherapy to the
      margins of resected brain tumor cavities.
AB  - OBJECT: The objectives of this study were to evaluate the safety and performance
      of a new brachytherapy applicator in the treatment of resected brain tumors in a
      canine model. METHODS: The brachytherapy applicator is an inflatable balloon
      catheter that is implanted in the resection cavity remaining after a brain tumor
      has been debulked. After implantation the balloon is inflated with Iotrex, a
      sterile solution containing organically bound iodine-125. The low-energy photons
      emitted by the iodine-125 deposit a therapeutic radiation dose across short
      distances from the surface of the balloon. After delivery of a prescribed
      radiation dose to the targeted volume, the radioactive fluid is retrieved and the
      catheter removed. Small resections of the right frontal lobe were performed in
      large dogs. Magnetic resonance (MR) images were obtained and used to assess
      tissue response and to measure the conformance between the resection cavity wall
      and the balloon surface. In four animals a dose ranging from 36 to 59 Gy was
      delivered. Neurological status and histological characteristics of the brain were
      assessed in all dogs. Implantation and explantation as well as inflation and
      deflation of the device were easily accomplished and well tolerated. The device
      was easily visualized on MR images, which demonstrated the expected postsurgical
      changes. The resection cavity and the balloon were highly conformal (range 93
      100%). Histological changes to the cavity margin were consistent with those
      associated with surgical trauma. Additionally, radiation-related changes were
      observed at the margins of the resection cavity in dogs in which the brain was
      irradiated. CONCLUSIONS: This balloon catheter and 125I radiotherapy solution
      system can safely and reliably deliver radiation to the margins of brain cavities
      created by tumor resection. Results of this study showed that intracranial
      pressure changes due to balloon inflation and deflation were unremarkable and
      characteristic of the imaging properties and radiation safety profile of the
      device prior to its clinical evaluation. Clinically relevant brachytherapy
      (adequate target volume and total dose) was accomplished in all four animals
      subjected to treatment.

PMID- 11838810
TI  - Multiple system Erdheim-Chester disease with massive hypothalamic-sellar
      involvement and hypopituitarism.
AB  - Erdheim-Chester disease (ECD) is a rare multiple system histiocytosis that is
      characterized pathologically by xanthogranulomatous infiltrates and
      radiologically by symmetrical sclerosis of long bones. The diagnosis is often
      confirmed by biopsy of bone or of orbital or retroperitoneal soft tissue.
      Intracranial involvement is rare. The authors report a case of ECD in which the
      diagnosis was made after biopsy of a hypothalamic mass. The mass had been
      discovered during a workup for panhypopituitarism in a 55-year-old man with
      urological and bone disease. Aside from diabetes insipidus, other features of
      pituitary insufficiency have seldom been reported and no patients have presented
      with a hypothalamic tumor. The endocrinological and neurological aspects of ECD
      are discussed, as is its differential diagnosis. Reported cases of the disorder
      associated with hypopituitarism or found during biopsy of central nervous system
      structures are also reviewed.

PMID- 11838811
TI  - Corticotroph carcinoma of the pituitary: a clinicopathological study. Report of
      four cases.
AB  - To understand the relationship between pituitary adenoma and carcinoma, four
      adrenocorticotropic hormone-producing pituitary adenomas and corresponding
      metastatic carcinomas were studied. All were functional macroadenomas (three
      cases of Nelson syndrome and one of Cushing disease) that initially invaded the
      sella turcica and occurred in women ranging in age from 17 to 66 years (mean 45
      years). Metastases (two craniospinal and two systemic) occurred after latency
      periods of 6 to 13 years. Histological specimens were immunostained for pituitary
      hormones, Ki-67 antigen (MIB-1), p53 and p27 proteins, D-type cyclins, and
      glucocorticoid receptor messenger (m)RNA. The DNA content of the specimens was
      assessed using Feulgen stain. Reactivities were quantified by digital image
      analysis. Primary/recurrent lesions and metastatic tumors differed according to
      their respective mean mitotic indices (1.2/10 hpf compared with 4.3/10 hpf), MIB
      1 labeling (1.7% compared with 8%), p53 staining (37.3% compared with 49.9%), and
      p27 labeling (48% compared with 25%). Cyclin D, immunoreactivity provided no
      prognostically significant information. Glucocorticoid receptor mRNA was detected
      in all cases. Results of a ploidy analysis were variable and nonprognostic. In
      keeping with the 2000 World Health Organization classification of endocrine
      neoplasms, our findings support the concept that primary tumors that exhibit
      mitotic activity, an increased (> 3%) MIB-1 labeling index, and/or p53
      immunoreactivity should be termed "atypical adenomas" to denote their aggressive
      potential and the possibility of future malignant transformation.

PMID- 11838812
TI  - Symptomatic osteolipoma of the tuber cinereum. Case report.
AB  - The authors present a case of an ossified lipoma located at the tuber cinereum.
      Intracranial osteolipomas are rare lesions that occur in the region of the tuber
      cinereum. Almost all reported cases have been incidental autopsy findings. This
      report, however, involves a young girl who presented with an ovarian cyst and
      signs of precocious puberty, in whom a typical osteolipoma was surgically
      removed. This is the first case of hypothalamic osteolipoma presenting with
      endocrinological disturbances that has been published to date.

PMID- 11838813
TI  - Intrathecal and intraperitoneal germinomas occurring 20 years after total removal
      of a pineal teratoma. Case report.
AB  - In 1980, a 10-year-old boy was admitted to the authors' hospital with
      consciousness disturbance and vomiting. Computerized tomography (CT) scans
      revealed a pineal mass lesion and hydrocephalus. The tumor was totally removed
      and a ventriculoperitoneal (VP) shunt was inserted. Histological investigation of
      a surgical specimen revealed that it was a teratoma. Five years later, the
      patient was readmitted to the same institution with polyuria. Magnetic resonance
      (MR) imaging revealed a mass lesion in the suprasellar region. The patient
      received systemic chemotherapy, and the tumor disappeared; however, 2 years after
      the chemotherapy, MR imaging demonstrated a right lateral ventricular mass. The
      tumor was totally resected, and histopathological investigation revealed a
      teratocarcinoma. Three years after the chemotherapy, CT scanning revealed
      suprasellar and right lateral ventricular tumor recurrences, for which the
      patient received irradiation and chemotherapy. The tumors disappeared and the
      patient achieved complete remission that lasted longer than 10 years. On January
      25, 2000, however, he noticed hip pain. Lumbar MR imaging demonstrated a spinal
      tumor below L-4 and also an abdominal tumor. The abdominal tumor was totally
      removed, and the histological findings identified it as a germinoma. The patient
      received systemic chemotherapy and the tumor disappeared completely. The authors
      believe that the suprasellar tumor was a metachronous germinoma and that it had
      metastasized through the intrathecal route and the VP shunt.

PMID- 11838814
TI  - Dural marginal zone lymphoma with massive amyloid deposition: rare low-grade
      primary central nervous system B-cell lymphoma. Case report.
AB  - The authors report the case of a 63-year-old woman who presented with a primary
      dural extranodal marginal zone lymphoma (MZL) associated with massive kappa light
      chain amyloidosis of the meninges. Extranodal MZL is a low-grade B-cell lymphoma
      that may show variable degrees of plasmacytic differentiation. Like solitary
      plasmacytoma of soft tissue, which can also be associated with amyloid,
      extranodal MZL generally responds well to local therapy and has a good prognosis.
      It is important to distinguish these entities from high-grade primary central
      nervous system (CNS) B-cell lymphomas and more aggressive and/or widespread,
      potentially amyloidogenic conditions such as multiple myeloma, lympho
      plasmacytoid lymphoma, and chronic lymphocytic leukemia/small lymphocytic
      lymphoma. To the authors' knowledge this is the first reported case of dural MZL
      associated with massive meningeal amyloid deposition. Extranodal MZL is a rare
      low-grade primary CNS B-cell lymphoma that may be associated with amyloidosis. It
      should be considered in the differential diagnosis of CNS lymphoproliferative
      lesions and CNS amyloidosis.

PMID- 11838815
TI  - Rescue balloon procedure for an emergency situation during coil embolization for
      cerebral aneurysms. Technical note.
AB  - In this article the authors describe a rescue balloon procedure for coil
      implantation in three cases. In each patient, the coil seemed likely to unravel.
      The coils stretched when attempts were made to remove the partially implanted but
      trapped device. The inflation of a nondetachable microballoon in front of the
      aneurysm orifice allowed the surgeons to complete implantation of the coil and to
      avoid a more forceful and potentially harmful retrieval. This rescue balloon
      method may be useful for emergency situations, such as coil stretching with or
      without migration.

PMID- 11838816
TI  - Statistical techniques and vasospasm.

PMID- 11838817
TI  - Vasospasm.

PMID- 11838818
TI  - Interactive magnetic resonance imaging.

PMID- 11838819
TI  - Diagnosis and measurement of adolescent depression: a review of commonly utilized
      instruments.
AB  - We surveyed 160 recent studies of adolescent depression (publication dates ranged
      from March 1996 to August 2000) and identified 33 different diagnostic and
      symptom measurement instruments being used by various investigators. We also
      found that more than one in three of the studies measuring depressive symptom
      severity in adolescents relied on instruments designed for use with adults. We
      then reviewed in detail the design features and psychometric properties of the 12
      instruments most commonly used in studies of adolescent depression and attempted
      to characterize their strengths and weaknesses. Our main conclusions are as
      follows: Too many different instruments are being used by investigators,
      presumably due to a lack of consensus as to which are the most valid and reliable
      tools. Instruments designed for use in adults and never validated in adolescent
      populations are frequently used with no evidence for their developmental
      sensitivity. Many studies are using instruments that demonstrate substantial
      weaknesses in validity and/or reliability. The need for a parsimonious, easily
      administered, valid, and reliable tool(s) to diagnose and measure symptom
      severity in adolescent depression has not yet been met.

PMID- 11838820
TI  - Methodological issues in designing a multisite trial of risperidone in children
      and adolescents with autism.
AB  - OBJECTIVE: To describe the methodological challenges and decisions made in
      developing a multisite, controlled study of risperidone in children and
      adolescents with autism. METHODS: Review the design considerations for clinical
      trials in children with autistic disorder accompanied by severe tantrums,
      aggressive and/or self-injurious behaviors. These design considerations include
      the definition of inclusion criteria that are relevant to clinical practice and
      matching study design to the goal of evaluating short- and long-term effects.
      Additional ethical and scientific issues concern the length of trial and sample
      size. RESULTS: We undertook a short-term, placebo-controlled study to evaluate
      the efficacy and safety of risperidone in children and adolescents with autistic
      disorder. This trial design was followed by an extended open-label maintenance on
      risperidone to confirm durability of treatment effects and to monitor safety.
      Finally, a placebo-controlled discontinuation study tested the need for
      continuous treatment. CONCLUSIONS: In the absence of standard pharmacological
      treatment for children with autistic disorder, a placebo-controlled study remains
      the most appropriate method of testing efficacy and safety. The clinical
      relevance of this study is enhanced by the addition of an extended maintenance
      phase followed by a placebo discontinuation.

PMID- 11838821
TI  - Prolactin levels in young children with pervasive developmental disorders during
      risperidone treatment.
AB  - Although hyperprolactinemia is a common side effect during risperidone treatment
      in adult patients, no information is available on young children. The aim of this
      study is to report on serum prolactin levels in 25 young autistic children (22
      males and 3 females, age range 3.9-7 years, mean age 4.10 years) during treatment
      with risperidone (dosage range 0.25-0.90 mg/day, mean dosage 0.52 mg/day).
      Prolactin levels were measured at baseline and after 10 weeks of treatment. The
      clinical outcome measure used was the Clinical Global Impression-Improvement.
      Serum prolactin was 9.77 +/- 3.94 ng/mL at baseline and 25.92 +/- 13.9 ng/mL
      during the 10th week of treatment (p < 0.001). Six children (24%) showed
      prolactin levels lower than 15 ng/mL, which is the upper normal level; eight
      children (28%) had prolactin levels higher than two times the upper limit (30
      ng/mL). Hyperprolactinemia did not show significant correlations with age,
      weight, or risperidone dosage. There was no relation with clinical outcome. Dose
      reduction of risperidone resulted in a decrease of prolactin levels. None of the
      children showed clinical signs of hyperprolactinemia. Given the paucity of
      available data on potential effects of long-term hyperprolactinemia, a monitoring
      of prolactin during treatment with risperidone and other typical and atypical
      antipsychotics may be warranted.

PMID- 11838822
TI  - Methodological complexities in the diagnosis of major depression in youth: an
      analysis of mother and youth self-reports.
AB  - OBJECTIVE: Considering the well-documented low level of agreement between youth
      and parent reports on the diagnosis of major depressive disorder (MDD),
      uncertainties remain as to the informativeness of discrepant youth and parent
      reports in clinical studies. To this end we evaluated whether morbidity and
      functional correlates on the diagnosis of MDD in youth vary by informant source.
      METHODS: The sample consisted of 186 pairs of independently assessed mother and
      youth self-reports on the diagnosis of MDD using structured diagnostic interviews
      ascertained in a large study of youth with and without attention deficit
      hyperactivity disorder of both genders. Subjects were also assessed on measures
      of interpersonal, school, and family functioning as well as prior treatment
      history. RESULTS: The diagnosis of MDD endorsed by youth self-report only when
      compared with that reported by the mother was characterized by significantly:
      shorter duration episode, later age at onset, milder depression-associated
      impairment, less impairment in interpersonal functioning, lower rates of comorbid
      disorders, and decreased likelihood to receive any course of treatment for
      depression. The morbidity and dysfunction associated with MDD varied
      significantly by informant source, and followed a dose-response association with
      the highest morbidity associated with the concurrent reports of the youth and the
      mothers, followed by mother report alone, with the least morbidity and
      dysfunction when endorsed by youth alone. CONCLUSIONS: These findings suggest
      that exclusive reliance on youth self-reports may identify a mild form of
      depression associated with limited morbidity and disability compared with that
      identified by parental reports.

PMID- 11838823
TI  - Adjunctive antipsychotic treatment is necessary for adolescents with psychotic
      mania.
AB  - Adolescents with acute psychotic mania were treated with lithium and adjunctive
      haloperidol as part of a lithium efficacy study. If the psychosis completely
      resolved, haloperidol was discontinued after 1 week of therapeutic lithium
      levels. Our first five subjects experienced a rapid exacerbation of symptoms,
      which responded to restarting haloperidol. A longer duration of adjunctive
      antipsychotic treatment is necessary in adolescents with bipolar psychosis.

PMID- 11838824
TI  - A study of quetiapine: efficacy and tolerability in psychotic adolescents.
AB  - OBJECTIVE: To study the effectiveness, safety, and tolerability of quetiapine in
      adolescents with psychotic disorders. METHODS: This study was an 8-week, open
      trial using quetiapine with 15 adolescents, ages 13-17 years, mean age 15.1
      years, with a diagnosis of a psychotic disorder. Our primary instruments focused
      on psychotic symptomatology as measured by the Brief Psychiatric Rating Scale
      (BPRS), Clinical Global Impression (CGI), Positive and Negative Syndrome Scale
      (PANSS), and the Young Mania Rating Scale (YMRS). Other measures included adverse
      events, clinical laboratory tests, vital signs, electrocardiogram (ECG),
      extrapyramidal (EPS) measures, and ophthalmologic examination. RESULTS:
      Quetiapine significantly reduced psychotic symptoms as measured by the BPRS,
      PANSS, YMRS, CGI, and CGI Severity of Illness scale. The average weight gain was
      4.1 kg. After correction for expected weight gain, the mean weight gain over the
      8-week period was 3.4 kg. Prolactin and cholesterol remained unchanged. Trends
      were found for a decrease in T4 and an increase in thyroid-stimulating hormone.
      Common adverse effects were somnolence, agitation, drowsiness, and headache. No
      significant findings were noted on repeat ECGs, EPS measures, or ophthalmic
      examination. The final average treatment dose was 467 mg/day (range 300-800
      mg/day). CONCLUSIONS: Quetiapine is suggested to be effective treatment of youths
      with psychotic disorders and to have a favorable side-effect profile.

PMID- 11838825
TI  - Atypical antipsychotic overdose in the pediatric population.
AB  - Risperidone is an atypical antipsychotic medication commonly used to treat
      psychotic illnesses in adults. It is being used with increasing frequency in
      children and adolescents, even though it has yet to be approved for use in this
      population by the Food and Drug Administration. There are few reports in the
      literature regarding its safety in those younger than 18 years of age. We present
      the case of a 15-year-old who ingested 110 mg of risperidone in a suicide attempt
      and developed only transient lethargy, hypotension, and tachycardia without any
      other significant effects. We review the literature regarding risperidone
      overdose in all age groups and review the current literature regarding pediatric
      overdose with the other atypical antipsychotics currently available in the United
      States. From those cases it seems that special care may be warranted with all
      pediatric cases of atypical antipsychotic overdose, including monitoring in a
      high-intensity clinical setting to manage potential respiratory or cardiac
      difficulties.

PMID- 11838826
TI  - Treatment of risperidone-induced hyperprolactinemia with a dopamine agonist in
      children.
AB  - BACKGROUND: Risperidone, a potent antagonist of both serotonergic (5HT2A) and
      dopaminergic D2 receptors is associated with hyperprolactinemia in adults and
      children. Chronically elevated prolactin levels in children with prolactinomas
      may be associated with arrested growth and development resulting in either
      delayed puberty or short stature. These possibilities stress the importance of
      developing a safe and effective approach to drug-induced hyperprolactinemia in
      youth. We report the successful treatment of risperidone-induced
      hyperprolactinemia with cabergoline in youth. METHODS: We undertook a
      retrospective case review of four children with risperidone-induced
      hyperprolactinemia treated with cabergoline. RESULTS: Four males (age 6-11 years)
      with Diagnostic and Statistical Manual of Mental Disorders (fourth edition)
      bipolar disorder or psychoses, with risperidone-induced elevations in serum
      prolactin levels (57.5-129 ng/mL, normal 5-15 ng/mL), were treated with
      cabergoline (mean dose 2.13 +/- 0.09 mg/week). When serum prolactin levels
      normalized in all four subjects (mean 11.2 +/- 10.9 ng/mL), the cabergoline dose
      was reduced to 1 mg/week in three of four subjects. The mean duration of therapy
      with cabergoline was 523.5 +/- 129.7 days, and the mean duration of therapy with
      risperidone was 788.5 +/- 162.5 days. Cabergoline was well tolerated without
      adverse effects. CONCLUSIONS: Cabergoline may be useful for the treatment of
      risperidone-induced hyperprolactinemia in youth; however, further research is
      needed.

PMID- 11838827
TI  - Risperidone-induced prolonged erections following the addition of lithium.

PMID- 11838829
TI  - The Finnmark Study. A prospective population study of the social support buffer
      hypothesis, specific stressors and mental distress.
AB  - BACKGROUND: According to the buffer hypothesis, social support or social network
      may affect mental health by buffering the negative effect of stress on mental
      health. Previous studies have mostly been cross-sectional or have been done on
      selected populations, and the results have been conflicting. METHODS: The buffer
      hypothesis was tested in three population-based health surveys which took place
      in 1987, 1990 and 1993 in five coastal municipalities in Finnmark, Norway. All
      persons aged 40-62 years and a random sample of those aged 20-39 years were
      invited, and 77%, 74% and 70% attended the three health surveys, respectively.
      Those who had attended the health surveys more than once and had answered the key
      questions about mental health and social network, social support (measured both
      as instrumental support as well as emotional support) and stress were included in
      the analyses. Stress was divided into acute stress, (somatic stress, civil stress
      and work stress) and chronic stress (having a chronic disease, disability
      pension, being a single parent or providing long term nursing care for someone in
      the family). Growth curve analyses using mental distress as the dependent
      variable were used, analysing the interactional effects of various types of
      stressors and social network or social support. RESULTS: When all possible
      stressors and the sum of social network/social support were taken into
      consideration, total social support/network buffered the deteriorating effect of
      total stressor score upon mental health. The effect was weak but significant, and
      stronger for women than men. When each stressor was analysed separately, only a
      significant buffer effect of social network could be detected for work stress.
      For one of the chronic stressors, receiving a disability pension, a buffer effect
      could be demonstrated for both social network and instrumental support.
      CONCLUSION: The results provide some support for the buffer hypothesis, and
      indication of specificity in the interactions between stressor and social
      network/social support was found.Women, in general, had a larger buffering effect
      from their social network than men.

PMID- 11838828
TI  - Does socioeconomic status predict course and outcome in patients with psychosis?
AB  - BACKGROUND: We examined the relationship between socioeconomic status (SES) and
      course and outcome of patients with psychosis. Two hypotheses were examined: a)
      patients with higher best-ever SES will have better course and outcome than those
      with lower best-ever SES, and b) patients with greater downward drift in SES will
      have poorer course and outcome than those with less downward drift. METHOD: Data
      were drawn from the baseline and 2-year follow-up assessments of the UK700 Case
      Management Trial of 708 patients with severe psychosis. The indicators of SES
      used were occupational status and educational achievement. Drift in SES was
      defined as change from best-ever occupation to occupation at baseline. RESULTS:
      For the baseline data highly significant differences were found between best-ever
      groups and negative symptoms (non-manual vs. unemployed--coef -10.5, p=0.000, 95%
      CIs 5.1-15.8), functioning (non-manual vs. unemployed--coef -0.6, p=0.000, 95%
      CIs 0.3 to -0.8) and unmet needs (manual vs. unemployed - coef 0.5, p=0.004, 95%
      CIs 0.2-0.9). No significant differences between best-ever groups were found for
      days in hospital, symptoms, perceived quality of life and dissatisfaction with
      services. Significant differences for clinical and social variables were found
      between drift and non-drift SES groups. There were no significant findings
      between educational groups and clinical and social variables. CONCLUSIONS: Best
      ever occupation, but not educational qualifications, appeared to predict
      prognosis in patients with severe psychosis. Downward drift in occupational
      status did not result in poorer illness course and outcome.

PMID- 11838830
TI  - Suicidal ideation in the Finnish general population. A 12-month follow-up study.
AB  - BACKGROUND: The epidemiology of suicidal ideation has remained a relatively
      unstudied area. The aim of this study was to investigate the incidence,
      prevalence and persistence of and recovery from suicidal ideation in a sample of
      the Finnish general population. METHODS: Postal questionnaires including the Beck
      Depression Inventory (BDI) were mailed to the study subjects (n = 1,593) at
      baseline and on follow-up after 12 months. The suicidality item of BDI was used
      to screen suicidal ideation. RESULTS: The 12-month incidence (4.6%) and
      prevalence of suicidal ideation (14.7%) were higher in men than in women (3.1%
      and 9.2%, respectively). Sixty-nine per cent of those men and 59% of those women
      who had suicidal ideation at baseline continued to have suicidal thoughts on
      follow-up. Suicidal ideation and the severity of depression associated strongly.
      Over half of the men and women who had persistent suicidal ideation had not
      visited any health services for help with psychological distress during the 12
      month follow-up period. Daily smoking associated with a decreased probability of
      recovery from suicidal ideation. CONCLUSIONS: Suicidal ideation is common and
      persistent at the population level. Seeking professional help for depression with
      suicidal tendencies is disproportionately low in relation to the high prevalence
      of suicidal ideation.

PMID- 11838831
TI  - Australian general practice and the meeting of needs for mental health care.
AB  - BACKGROUND: This report, drawing on a national epidemiological survey conducted
      in 1997, examines the role of Australian medical general practitioners (GPs) in
      responding to needs for mental health care. METHODS: We analysed data from the
      Australian National Survey of Mental Health and Wellbeing (NSMHWB). The NSMHWB
      employed clustered probability sampling of all Australian adults, and 10,641
      participants were interviewed. The field questionnaire included modules of the
      Composite International Diagnostic Interview, and instruments assessing
      disability, service utilisation and perceived needs for care. RESULTS: Eighty
      four percent of people with a mental disorder consulted a GP in the year prior to
      survey, but only 29% consulted in relation to a mental health problem. GP
      services were seen as more responsive to needs for medication, counselling and
      information than needs for social interventions and skills training. People with
      perceived needs for counselling were more likely to consult with other providers,
      either as alternative or additional consultations to those with a GP. Counselling
      needs were reported as less well met when people saw a GP alone than when
      consulting other service providers. CONCLUSIONS: Many people with mental health
      problems attend primary medical care practitioners without presenting these
      problems to their physicians. When they do present, perceived needs for
      medication are rated as well met, but there is substantial unmet perceived need
      for interventions in social and occupational domains. Perceived needs for
      counselling are less well met where the GP is the sole provider. To close these
      identified gaps calls for improvements in primary care physicians' skills and
      effective collaborative models with other providers.

PMID- 11838832
TI  - Carers and community mental health services.
AB  - BACKGROUND: There is a growing appreciation of the role and needs of carers for
      people with mental health problems. Carers are a diverse group, including
      partners, relatives and friends who are seen as such by service users. METHODS:
      Sixty-four carers of people with severe mental health problems served by four
      different mental health care providers were interviewed using the Experiences of
      Care-giving Inventory. The districts were selected to differentiate services that
      are targeted at more severely impaired users from those that include a wider
      spectrum, and to contrast services that have greater integration between health
      and social care providers with those whose health and social care agencies
      operate relatively discretely. RESULTS: In the two districts where service users
      had more severe mental health problems, carers worried more about negative
      symptoms and thought less about good aspects of the caring relationship. In the
      two districts where health and social services worked more closely together,
      carers worried significantly less about the need to back up services.
      CONCLUSIONS: These findings suggest that service organisation can affect carers,
      in particular that integration between health and social care for people with
      mental health problems may benefit carers in ways that were hitherto unproven.
      They highlight the needs of carers for younger people. They show that the ECI is
      a useful instrument in measuring the impact of caring for people with severe
      mental health problems.

PMID- 11838833
TI  - Stroke and mental health care: a record linkage study.
AB  - BACKGROUND: Stroke is associated with psychiatric morbidity but little is known
      about mental health care use in stroke patients. METHOD: A probability record
      linkage study was conducted linking stroke cases admitted to a teaching hospital
      serving a catchment area between 1987 and 1995 with records from a psychiatric
      case register covering the same area. RESULTS: Stroke patients had a more than
      twofold increased risk of contact with mental health care than individuals in the
      general population (yearly prevalences of respectively 88 and 39 per 1000; risk
      ratio 2.24; 95 % CI 2.04-2.45). One-third of all stroke admissions had had mental
      health care before and more than half had had mental health care after the
      stroke. In the year of admission for stroke, the probability of receiving mental
      health care was highest, while in the more remote years the risk was lower.
      CONCLUSION: Stroke is associated with an increased probability of contact with
      mental health services. The pattern of mental health care of a stroke patient is
      different from that of other mental health patients: more episodic and
      concentrated around the time of admission for stroke.

PMID- 11838834
TI  - Prevalence of depression and depression recognition in nursing homes.
AB  - BACKGROUND: The aim of this study was to estimate the prevalence of depression
      among nursing home residents, and the extent of depression recognition among
      nursing home staff. Random samples totaling 319 nursing home residents, drawn
      from a simple random sample of six downstate New York nursing homes were
      evaluated psychiatrically for depression. Samples of nurse aides, nurses and
      social workers also assessed the same residents for the presence of depressive
      symptomatology. METHOD: Psychiatrists assessed residents using the Diagnostic and
      Statistical Manual of Mental Disorders (DSM-III-R) criteria. Depression measures
      used were the Cornell Scale for Depression in Dementia, the Feeling Tone
      Questionnaire, the Hamilton Depression Rating and the Structured Clinical
      Interview for DSM-III-R Personality Disorders Scale. Nursing and social services
      staff assessed residents using Depression Recognition Measures. RESULTS: Based on
      psychiatric evaluation, the prevalence estimate for probable and/or definite
      major depressive disorder among testable subjects was 14.4% (95% CI of 10.6%
      19.3%); 15.4% were not able to be assessed due to their refusal, impairment of
      consciousness, or severe physical illness. The estimate for minor depression was
      16.8% (95% CI of 12.6%-21.9%). The prevalence of significant depressive
      symptomatology (including the category of possible depression) was 44.2% (95% CI
      of 38.2%-50.3%). The corresponding estimates of any depression were 19.7% for
      social workers, 29% for nurses and 32.1% for nurse aides. CONCLUSIONS: The
      prevalence of depressive disorders among nursing home residents is high;
      depression recognition is relatively low, with only 37%-45% of cases diagnosed by
      psychiatrists recognized as depressed by staff. A structured Depression
      Recognition Scale increased the rates of recognition (sensitivity of staff
      ratings) to 47%-55%, demonstrating the utility of the scale in increasing
      awareness of symptomatology.

PMID- 11838835
TI  - Arthritis health promotion versus comprehensive arthritis management. Is there a
      difference?

PMID- 11838836
TI  - In quest of the holy grail: efficacy versus effectiveness in rheumatoid
      arthritis.

PMID- 11838837
TI  - Susceptibility for and clinical manifestations of rheumatoid arthritis are
      associated with polymorphisms of the TNF-alpha, IL-1beta, and IL-1Ra genes.
AB  - OBJECTIVE: To analyze the association of genetic polymorphisms of pro
      inflammatory cytokines with rheumatoid arthritis (RA) in comparison with healthy
      controls from Northern Sweden and the potential contribution of these genetic
      variants for disease severity and development of cardiovascular complications.
      METHODS: Polymerase chain reaction amplification was used for analysis of TaqI
      restriction fragment length polymorphism (RFLP) of interleukin-1 beta (IL-1beta),
      variable tandem repeat polymorphism of IL-I receptor antagonist (IL-1Ra) gene and
      NcoI RFLP at position -308 of tumor necrosis factor-alpha (TNF-alpha) gene. One
      hundred and fifty-four patients with RA, 42 men and 112 women, were consecutively
      recruited into the study through the Department of Rheumatology. RESULTS: The
      allele A1 of TNF-alpha was more common in the patient group (p < 0.01; OR =
      1.62). Patients having the genotype A1A2 seemed to develop more severe disease
      compared with patients with A1A1 genotype: they were younger at disease onset (p
      < 0.05), had a higher accumulated disease activity (p < 0.05) and worse
      functional class (p < 0.05). Patients with genotype A2A2 of IL- 1beta had higher
      accumulated disease activity score than patients with A1A1 and A1A2 (p < 0.05).
      The allelic combination Al IL-1beta/A2 IL-1Ra was less prevalent in RA patients
      who developed cardiovascular complications (p < 0.005; OR = 0.20). CONCLUSIONS:
      The Al allele of TNF-alpha associates with RA. Genotypes A1A2 of TNF-alpha and
      A2A2 of IL-1beta are associated with more severe disease. The allelic combination
      A1IL-1beta/A2 IL-1Ra is less often present in RA patients who developed
      cardiovascular complications.

PMID- 11838838
TI  - CD4 coating, but not CD4 depletion, is a predictor of efficacy with primatized
      monoclonal anti-CD4 treatment of active rheumatoid arthritis.
AB  - OBJECTIVE: Double blind studies were conducted with the anti-CD4 monoclonal
      antibody (Mab) keliximab in patients with active, stable rheumatoid arthritis
      (RA), to confirm preliminary evidence of efficacy and safety from open.
      uncontrolled studies. METHODS: We enrolled 136 and 186 patients into 2
      consecutive, randomized, double blind trials, with similar populations [apart
      from inclusion of disease modifying antirheumatic drug (DMARD)-naive patients in
      Study 2]. Patients received 4 weeks intravenous placebo or keliximab [40, 80,
      120, or 140 mg twice weekly (bw), or 240 mg once weekly (ow)]. The primary
      endpoint was the American College of Rheumatology (ACR) 20 response criteria, one
      week after the end of treatment. RESULTS: ACR 20 response rates in Study I were
      19%, 42%, 51%*, and 69%* (*p < 0.05 compared to placebo), with placebo, 40, 80,
      or 140 mg keliximab bw, respectively. The response rates in Study 2 were 30%,
      39%, 46% and 47% with placebo, 80 or 120 mg bw, or 240 mg keliximab ow,
      respectively. In the 2 studies, there was a dose dependent increase in peripheral
      blood CD4+ T cell coating with keliximab, but a different pattern of CD4
      depletion was seen. While only 12% of keliximab treated patients in Study I had
      CD4 counts below 250 cells/mm3 at the end of the treatment period, 47% fell below
      this level in Study 2. Clinical response was not correlated with CD4 depletion,
      but was correlated with CD4+ T cell coating with keliximab. CONCLUSION: Coating
      of peripheral blood CD4+ T cells with keliximab, but not CD4 depletion, is a
      determinant of clinical response.

PMID- 11838839
TI  - Constitutive expression of angiopoietin-1 and -2 and modulation of their
      expression by inflammatory cytokines in rheumatoid arthritis synovial
      fibroblasts.
AB  - OBJECTIVE: Angiopoietin- I (Ang-1) and Ang-2 are ligands for the receptor
      tyrosine kinase, Tie-2. Ang-1, a Tie-2 agonist, may have a vascular stabilizing
      role in angiogenesis, while Ang-2, an endogenous antagonist of Tie-2, may have an
      early role in angiogenesis, destabilizing existing vasculature. We show that
      these ligands are expressed by rheumatoid synovial fibroblasts (RSF) and
      investigate whether their expression was modulated by proinflammatory cytokines
      present in the joint in rheumatoid arthritis (RA). METHODS: Using quantitative
      PCR we determined the level of expression of these 2 ligands in RSF and chronic
      inflamed synovial tissue. The level of expression of these ligands after
      treatment with proinflammatory cytokines and hypoxia was also determined.
      RESULTS: We observed constitutive expression of Ang-1 and Ang-2 in RSF and
      chronic inflamed synovial tissue. Ang-1 was the most highly expressed ligand in
      late stage RA synovial fibroblasts; however, in chronic inflamed synovial tissue,
      Ang-2 was predominant and was expressed at strikingly high levels (70 to 120-fold
      increase). We observed that tumor necrosis factor-alpha (TNF-alpha) and
      transforming growth factor-beta (TGF-beta), but not interleukin 1beta or hypoxia,
      stimulated Ang-1 gene expression in RSE This was confirmed at the protein level
      as media from TNF-alpha treated RSF resulted in increased autophosphorylation of
      Tie-2. In contrast, TNF-alpha and TGF-beta had no effect on Ang-2 expression in
      RSF, but augmented expression of Ang-2 in normal synovial fibroblasts.
      CONCLUSION: The angiopoietins are important angiogenic factors constitutively
      present in RA, and their expression is modulated by certain cytokines. Ang-2 may
      have an important role in rheumatoid tissue where vigorous angiogenesis is
      occurring.

PMID- 11838840
TI  - Effect of direct angiogenesis inhibition in rheumatoid arthritis using a soluble
      vascular endothelial growth factor receptor 1 chimeric protein.
AB  - OBJECTIVE: We evaluated the effect of direct angiogenesis inhibition in synovium
      of patients with rheumatoid arthritis (RA), using a soluble vascular endothelial
      growth factor receptor 1 (VEGFR1) chimeric protein. METHODS: Dispased cells from
      active RA synovial tissues were cocultured on OP9 stromal cells. Control synovial
      tissues were obtained from patients with injury of the anterior cruciate
      ligament. Chimeric protein (30 microg/ml) of the extracellular domain of VEGFR1
      fused to the Fc portion of human IgG1 (VEGFR1-Fc) was added to culture medium.
      After 10 days, the cells were stained with anti-CD31 antibody and anti-Tie-2
      antibody. RESULTS: Endothelial cells from patients with active RA had high
      angiogenic growth capacity compared with controls. Proliferation of these
      endothelial cells was strongly suppressed by VEGFR1-Fc. Quantitative analysis
      revealed that VEGFR1-Fc inhibited angiogenesis in a dose dependent manner.
      CONCLUSION: VEGFR1-Fc is able to suppress angiogenesis in rheumatoid synovium,
      suggesting that direct inhibition of angiogenesis activity could serve as a novel
      therapeutic strategy to prevent progressive synovial hyperplasia and inflammatory
      reactions in active RA.

PMID- 11838841
TI  - Blood transfusion, alcohol use, and anthropometric risk factors for rheumatoid
      arthritis in older women.
AB  - OBJECTIVE: To evaluate whether blood transfusion, alcohol use, or anthropometric
      characteristics are risk factors for rheumatoid arthritis (RA) in older women.
      METHODS: These factors were evaluated in a prospective cohort study that was
      initiated in 1986, and included 31,336 women aged 55-69 years without a history
      of RA. Risk factor data were self-reported using a mailed questionnaire. Through
      1997, 158 cases of RA meeting at least 4 of 7 American College of Rheumatology
      criteria were identified and validated by medical record review. The relative
      risk (RR) and 95% confidence interval (CI) were used as the measure of
      association, and were adjusted for the potential confounding effects of age,
      marital status, smoking history, age at menopause, and use of estrogen
      replacement therapy. RESULTS: History of blood transfusion was inversely
      associated with RA (multivariate RR = 0.72; 95% CI 0.48-1.08), and this
      association was stronger for rheumatoid factor (RF) positive disease (RR = 0.59;
      95% CI 0.35-1.00). There were no associations for use of medications for hyper-
      or hypothyroidism or adult onset diabetes. Anthropometric factors (height,
      weight, body mass index, body fat distribution), leisure time physical activity,
      and alcohol use were not associated with risk of RA. CONCLUSION: A history of
      blood transfusion was inversely associated with RA, particularly RF positive RA.
      Anthropometric factors, physical activity, and alcohol use did not influence the
      risk of RA in this cohort of older women.

PMID- 11838842
TI  - Prescribing trends in disease modifying antirheumatic drugs for rheumatoid
      arthritis: a survey of practicing Canadian rheumatologists.
AB  - OBJECTIVE: To determine the prescribing and monitoring practices of disease
      modifying antirheumatic drugs (DMARD) for Canadian rheumatologists in their
      treatment of rheumatoid arthritis (RA). METHODS: A survey questionnaire was
      mailed to 279 rheumatologists with a 70% response rate after 2 mailings. RESULTS:
      Antimalarials are prescribed commonly, with the preference being
      hydroxychloroquine (HCQ). For antimalarials, 78% do not routinely monitor
      laboratory results. There was wide variability in monitoring for ocular
      complications. Thirty-eight percent of rheumatologists never do a baseline eye
      examination and 39% always do. All rheumatologists frequently use methotrexate
      (MTX) in RA. The reported mean maximum dose for MTX was 25.1 mg/week (range 7.5
      50), with 86% routinely using folate. Ninety-eight percent prescribe
      sulfasalazine (SSZ) for RA. Mean maximum dose prescribed for SSZ was 2.8 g/day.
      Most never used oral gold, while IM gold was used by 95%. Only 9% frequently use
      azathioprine in RA, to a mean maximum dose of 185 mg/day. Less commonly
      prescribed DMARD included cyclosporine (66% frequently; 25% never) and D
      penicillamine (2% frequently; 53% never). There was a wide range of what exactly
      was monitored with respect to laboratory tests, and at what frequency, for many
      of the DMARD. Nearly all (99%) used combination DMARD, the most popular
      combination being MTX-HCQ. There were some significant differences in treatment
      trends when comparing year of fellowship completion, but no sex or type of
      practice differences were found. Those completing fellowships prior to 1984 were
      more likely to prescribe azathioprine (p < 0.03), chloroquine (p < 0.01) and
      chronic steroids (p < 0.1) in RA. There was, however, regional variability in the
      use of IM gold and newer DMARD--they were most prescribed in Western Canada and
      least in Quebec. Cyclosporine was prescribed most frequently in Quebec compared
      to Western Canada and least in Ontario and the Atlantic Provinces. CONCLUSION:
      Canadian rheumatologists are fairly similar in their use of common DMARD and
      combination therapies in RA. There is variability in the use of some older
      medications including azathioprine and chloroquine, depending on when
      rheumatology training was completed, and use of some drugs varies by region.

PMID- 11838843
TI  - Disease modifying antirheumatic drugs in early rheumatoid arthritis: a longterm
      observational study.
AB  - OBJECTIVE: To investigate the effectiveness, toxicity, and drug survival in an
      observational longterm study of patients with early rheumatoid arthritis (RA).
      METHODS: Four hundred twenty-eight patients with early RA were investigated
      between January 1987 and December 1995. All patients had a disease duration of
      less than one year and had not been previously treated with any disease modifying
      antirheumatic drug (DMARD). The following drugs were introduced at the doses
      specified: hydroxychloroquine (HCQ) (200-400 mg/day), D-penicillamine (D-Pen)
      (500 mg/day), sulfasalazine (SSZ) (2-3 g/day), auranofin (6 mg/day),
      intramuscular gold (IM gold, 50 mg/week), methotrexate (MTX) (0.15 mg/kg/week,
      per os), cyclosporin A (CSA) (3 mg/kg/day), azathioprine (AZA) (2-3 mg/kg/day),
      cyclophosphamide (CYC) (1-2 mg/kg/day). RESULTS: Three hundred eighty-three
      patients were treated with one DMARD for at least 6 months. Sixty-five percent of
      patients were seropositive. The disease duration was 9.2 (3.1) months and the
      followup period of 12.7 (4.8) years, ranging from 7 months to 13 years. The drugs
      of first choice were: D-Pen (32%), HCQ (30%), MTX (21%), CSA (8%), and IM gold
      (7%). After the 2nd, 3rd, and 4th prescriptions, MTX was the most popular drug
      (27%), while D-Pen and HCQ were prescribed less frequently. The longest drug
      survival was seen in MTX treated patients, followed by CSA, without significant
      differences between them. D-Pen, HCQ, and IM gold had the largest dropout rate.
      The main causes for drug discontinuation were drug inefficacy (HCQ), followed by
      adverse drug reactions (D-Pen). CONCLUSION: It appears that MTX has the longest
      survival time, with CSA following in second place. The main reasons for
      discontinuation of treatment were drug inefficacy, followed by adverse drug
      reactions.

PMID- 11838844
TI  - Improvement in diagnosis of rheumatoid arthritis using dual indirect
      immunofluorescence and immunoblotting assays for antifilaggrin autoantibodies: a
      retrospective 3 year study.
AB  - OBJECTIVE: To determine the clinical usefulness of measuring antistratum corneum
      (ASC) and antifilaggrin autoantibodies (AFA) to discriminate between rheumatoid
      arthritis (RA) and other rheumatic or autoimmune diseases, using an indirect
      immunofluorescence (IIF) assay, along with a complementary immunoblotting
      technique (IB) when IIF detection of ASC was negative. METHODS: Sera from 346
      patients were studied: 189 sera from patients with RA seen in the same clinic, 92
      from patients with non-RA rheumatic diseases, 24 from nonrheumatic autoimmune
      diseases, and 41 from healthy blood donors. ASC and AFA were detected using IIF
      and IB, respectively. RESULTS: ASC detection using IIF showed a specificity of
      97.5% for RA with 44.4% sensitivity. When both IIF and IB techniques were used,
      sensitivity for RA increased significantly (up to 53.4%; p < 0.01) with no
      decrease in specificity (p < 0.01). CONCLUSION: These data confirm the usefulness
      of 2 different techniques performed simultaneously for detecting ASC/AFA, and the
      usefulness of these biological markers for discriminating between RA and other
      rheumatic diseases in clinical practice.

PMID- 11838845
TI  - Pulmonary hypertension in systemic lupus erythematosus: evaluation of clinical
      characteristics and response to immunosuppressive treatment.
AB  - OBJECTIVE: To clarify the clinical features of systemic lupus erythematosus (SLE)
      complicated with pulmonary hypertension (PH) and to evaluate the efficacy of
      immunosuppressive treatment. METHODS: Case records were reviewed for 194 patients
      with SLE who were admitted to Aoyama Hospital of Tokyo Women's Medical University
      between 1992 and 1999. There were 12 patients with PH [8 SLE and 4 SLE + systemic
      sclerosis (SSc) overlap syndrome]. These patients were compared with 59 age and
      sex matched patients with SLE for clinical characteristics and laboratory
      findings. The efficacy of treatments for PH was also evaluated. RESULTS: In our
      cohort of 194 patients with SLE, 6.2% had PH. The plasma thrombin-antithrombin
      III complex and plasma D-dimer levels were significantly higher in patients with
      PH compared with those without PH. Eight patients with PH (4 SLE and 4 SLE + SSc)
      were treated with corticosteroids (CS) +/- cyclophosphamide (CYC). Right
      ventricular systolic pressure (RVSP) was improved in 7 of 8 patients. In 6 of 7
      responders to the therapy, the treatment was started as soon as they were
      diagnosed with PH. PH relapsed in 2 patients treated with oral CS +/- CS pulse
      therapy, but their RVSP was decreased again by immunosuppressive treatment.
      CONCLUSION: CS +/- CYC was effective for PH associated with SLE.
      Immunosuppressive treatment should be performed during the early stage of PH to
      improve prognosis.

PMID- 11838846
TI  - Systemic lupus erythematosus disease activity index 2000.
AB  - OBJECTIVE: To describe the Systemic Lupus Erythematosus Disease Activity Index
      2000 (SLEDAI-2K), a modification of SLEDAI to reflect persistent, active disease
      in those descriptors that had previously only considered new or recurrent
      occurrences, and to validate SLEDAI-2K against the original SLEDAI as a predictor
      for mortality and as a measure of global disease activity in the clinic. METHODS:
      All visits in our cohort of 960 patients were used to correlate SLEDAI-2K against
      the original SLEDAI, and the whole cohort was used to validate SLEDAI-2K as a
      predictor of mortality. A subgroup of 212 patients with SLE followed at the Lupus
      Clinic who had 5 regular visits, 3-6 months apart, in 1991-93 was also included.
      An uninvolved clinician evaluated each patient record and assigned a clinical
      activity level. The SLEDAI score was calculated from the database according to
      both the original and modified definitions. RESULTS: SLEDAI-2K correlated highly
      (r = 0.97) with SLEDAI. Both methods for SLEDAI scoring predicted mortality
      equally (p = 0.0001), and described similarly the range of disease activity as
      recognized by the clinician. CONCLUSION: SLEDAI-2K, which allows for persistent
      activity in rash, mucous membranes, alopecia, and proteinuria, is suitable for
      use in clinical trials and studies of prognosis in SLE.

PMID- 11838847
TI  - Clinical and immunological factors associated with low lacrimal and salivary flow
      rate in patients with primary Sjogren's syndrome.
AB  - OBJECTIVE: To study which clinical and immunological factors may be associated
      with low salivary and lacrimal flow in patients with primary Sjogren's syndrome
      (SS). Are the lacrimal and salivary flows influenced by age of the patient, age
      at diagnosis, disease duration, or findings in the biopsies of the minor salivary
      glands, or are immunological factors of importance for reduced flow rates?
      METHODS: In total 72 patients (mean age 57 yrs and disease duration 13.5 yrs)
      with primary SS diagnosed according to the European classification criteria were
      evaluated objectively by serological testing and by measures of exocrine gland
      function, such as unstimulated whole saliva collection (UWSC) and by Schirmer I
      test. RESULTS: Salivary flow (UWSC) in 72 patients with primary SS correlated to
      the presence of antinuclear antibodies (ANA) (r = -0.32, p = 0.006) and to anti
      SSA/SSB (r = -0.31, p = 0.010). No such correlation was seen for the lacrimal
      flow, and there was no mutual correlation between lacrimal and salivary flow.
      UWSC was significantly lower in patients with anti-SSA versus those without anti
      SSA (1.63 ml vs 2.63 ml; p < 0.007), while such a significant difference was not
      observed in the presence versus absence of anti-SSB. The salivary and lacrimal
      flow was not significantly affected by age of the patient, and did not correlate
      to age at diagnosis, sex, disease duration, rheumatoid factor finding, or
      findings in minor salivary gland biopsies. CONCLUSION: Salivary flow in patients
      with primary SS was negatively correlated with immunological factors such as ANA
      and anti-SSA/SSB, in contrast to low lacrimal flow, where no such correlation was
      seen. There was no association of lacrimal and salivary flow with age of patient,
      age at diagnosis, disease duration, and findings in minor salivary gland
      biopsies. The results indicate that reduced salivary flow is closely associated
      with immunological factors, and is not associated with the age of the patient or
      infiltration of lymphocytes in salivary glands.

PMID- 11838848
TI  - Wegener's granulomatosis: survey of 701 patients in North America. Changes in
      outcome in the 1990s.
AB  - OBJECTIVE: To study the medical and socioeconomic impact of Wegener's
      granulomatosis (WG) in a large cohort (n = 701) of patients who are members of
      the international WG Support Group (WGSG). METHODS: Forty questions designed and
      validated by one of the authors and reviewed by the medical consultants of the
      WGSG International were mailed to 1690 patients with WG who are members of the
      WGSG; 701 (41%) patients returned the questions. Diagnosis of WG was self
      reported for purpose of this questionnaire. Study domains included demographic
      features, education, analysis of categories of medical care providers, organ
      system involvement, delay in diagnosis, frequency and sites of biopsies to assist
      in diagnosis, treatment outcome, familial association, disability, and financial
      effect. We compared some of these features in patients whose diagnosis was made
      in the 1970s, 1980s, or 1990s. RESULTS: In our cohort WG was slightly more
      prevalent in women (56%), particularly if the disease started at a younger age (9
      40 years). Peak age period at disease onset was 45-65 years. Ninety-eight percent
      of patients were Caucasian. Diagnosis of WG was usually made by a specialist, and
      the majority of patients received subsequent care by specialists. During the past
      decade only 7% of patients received a diagnosis of WG upon their first visit to a
      physician. A period of 3-12 months passed from onset of features of WG to
      achieving a diagnosis in the majority of patients. Compared to the period 1970
      90, in recent years fewer patients had biopsies performed for diagnostic
      purposes. This observation correlated with increased use of antineutrophil
      cytoplasmic antibodies. In the 1990s the most common reported therapy was
      combination of corticosteroids and cyclophosphamide (73%). Patients also reported
      initial therapy with methotrexate (11%), trimethoprim-sulfamethoxa-zole (32%),
      and azathioprine (5%). Patients rarely reported other family members with WG. In
      none of 12 WG patients who had a twin did the twin have WG. The survey did not
      identify any specific environmental exposure, occupation, or hobby that was
      overrepresented among patients. One hundred seventy-nine WG patients reported
      that their disease had a significant financial impact on their lives. CONCLUSION:
      Information from this survey of 701 patients is consistent with physician
      reported data about organ involvement, initial manifestations and therapy, and
      outcomes in WG. More WG patients in the 1990s were diagnosed after first
      physician encounter. This survey did not reveal any predisposing or inducing
      environmental or familial factors, and showed fewer patients become disabled and
      more were able to work full time.

PMID- 11838849
TI  - Novel genetic association of Wegener's granulomatosis with the interleukin 10
      gene.
AB  - OBJECTIVE: Wegener's granulomatosis (WG) is a necrotizing vasculitis
      characterized by clonal expansions of T cells and production of antibodies
      against proteinase 3. The disease is associated with expanded dinucleotide
      repeats in the cytotoxic T lymphocyte antigen 4 (CTLA-4) gene, suggesting that
      genetic variation(s) in T cell related gene(s) could contribute to the T cell
      hyperactivity in WG. We investigated the polymorphisms in the genes of 2
      cytokines, interleukin 4 (IL-4) and IL-10, which are essential for the
      polarization of T cells towards Th2 development and for the Ig production by B
      cells. METHODS: Polymorphisms in the genes coding for IL-10 and IL-4 were
      analyzed in 32-36 Swedish Caucasian patients and 109 ethnically matched healthy
      individuals. RESULTS: There was no association with the IL-4 gene. A CA repeat
      polymorphism in IL-10 gene, IL-10.G, was associated with the disease. This
      polymorphism has earlier been associated with high autoantibody production.
      CONCLUSION: Our results indicate that the IL-10 gene may influence the disease,
      perhaps by influencing the production of autoantibodies.

PMID- 11838850
TI  - Sex differences in temporal arteritis and polymyalgia rheumatica.
AB  - OBJECTIVE: Sex-specific differences in treatment outcomes have been observed in
      polymyalgia rheumatica (PMR) and temporal arteritis (TA), with a significantly
      longer course of treatment in women than in men. We analyzed whether these sex
      differences are related to differences in disease presentation and severity of
      the inflammatory response. METHODS: The records of 163 cases of PMR and/or TA
      diagnosed over a 15 year period were reviewed. A comparative study of clinical
      and laboratory features between men and women was performed. RESULTS: Of 163
      patients, 90 had isolated PMR and 73 had TA. Among patients with TA, 49 women and
      24 men were identified, with a ratio of 2. While there were no differences in the
      frequency of classic disease manifestations, the presence of constitutional
      syndrome (malaise, anorexia, and weight loss) and fever were significantly more
      frequent in women than in men. Of note, evaluation of laboratory measures at time
      of diagnosis also revealed more marked laboratory abnormalities reflecting
      inflammation in the female group. Among patients with isolated PMR, 58 women and
      32 men were identified, a ratio of 1.8. Comparing the clinical features at
      presentation, significant sex differences were also found, with a higher
      frequency of constitutional syndrome and lower values of hemoglobin in women.
      Moreover, women also had higher erythrocyte sedimentation rate values, and higher
      prevalence of fever and hepatic involvement, although the difference did not
      reach statistical significance. CONCLUSION: Modest differences were found in
      disease expression between women and men with TA and/or PMR. In both conditions,
      the inflammatory response seemed to be more severe in women. The strong
      inflammatory response in women could explain the longer duration of treatment
      reported in this subgroup of patients.

PMID- 11838851
TI  - The potential of ESSG spondyloarthropathy classification criteria as a diagnostic
      aid in rheumatological practice.
AB  - OBJECTIVE: The European Spondylarthropathy Study Group (ESSG) criteria for the
      classification of spondyloarthropathies (SpA) were developed with the aim of
      unifying and facilitating international medical communication. We assessed the
      potential of ESSG criteria as a diagnostic aid for rheumatology practices in
      terms of sex and prevalence rate. METHODS: Data from 2 similarly designed and
      developed studies conducted in France and Spain were examined. Data were obtained
      from 3,494 patients seen at rheumatology outpatient services (28 in each
      country). The sensitivity and specificity of each ESSG criterion (except the
      radiological one) were assessed in terms of sex and country. Patients were
      divided into 4 groups according to number of criteria present at the time of the
      study: Group I had neither inflammatory spinal pain (ISP) nor synovitis; Group 2
      had ISP and/or synovitis; Group 3 ISP and/or synovitis plus one additional
      criterion; Group 4 ISP and/or synovitis plus more than one additional criterion.
      The predictive value was determined by using different prevalence rates. RESULTS:
      A prevalence of 27.6% for male and 8.0% for female patients was found at Spanish
      services; prevalence in French services was 9.1% males and 3.2% females. No
      significant differences in sensitivity and specificity for each sex between
      French and Spanish individuals were detected; the overall sensitivity and
      specificity were similar for men and women. By contrast, there were differences
      between patients from the 2 countries regarding individual ESSG criteria; thus,
      inflammatory spinal pain and synovitis were less specific in the female and male
      Spanish patients, respectively, relative to the French patients. CONCLUSION: ESSG
      criteria can be used meaningfully to aid diagnosis when the prevalence of SpA
      exceeds 10% and the patient meets more than one of the additional criteria, or
      when prevalence exceeds 30% and the patient meets only one additional criterion.

PMID- 11838852
TI  - Local ice therapy during bouts of acute gouty arthritis.
AB  - OBJECTIVE: To evaluate the effect of local application of ice on duration and
      severity of acute gouty arthritis. METHODS: Nineteen patients with acute gout
      were enrolled and randomized into 2 groups. Group A (n = 10) received topical ice
      therapy, oral prednisone 30 mg PO tapered to 0 over 6 days and colchicine 0.6
      mg/day. Group B was the control group (n = 9), given the same regimen but without
      the ice therapy. The patients were followed for one week. RESULTS: The mean
      reduction in pain for those patients treated with ice therapy was 7.75 cm (on 10
      cm visual analog scale) with standard deviation +/- 2.58 compared with 4.42 cm
      (+/- SD 2.96) for the control group. Using a Wilcoxon rank-sum test there was a
      significant difference (p = 0.021 ) in pain reduction between the ice therapy and
      control groups. Joint circumference and synovial fluid volume also tended to be
      more effectively reduced after one week of therapy in the ice group compared with
      controls, but these did not achieve statistical significance. CONCLUSION: The
      group treated with ice had a significantly greater reduction in pain compared
      with the control group. Although the clinical improvement was impressive, due to
      the small sample size we could not show statistically significant improvement in
      all the variables that tended to suggest that effect was more than simply
      analgesic. Cold applications may be a useful adjunct to treatment of acute gouty
      arthritis.

PMID- 11838853
TI  - Influence of weather conditions on rheumatic pain.
AB  - OBJECTIVE: To evaluate the influence of the weather in Cordoba City, Argentina,
      on pain in patients with rheumatic pain; to correlate different climate variables
      with the patients' impression of weather sensitivity; and to assess correlations
      between pain and climate conditions on 5 days preceding and following painful
      episode. METHODS: Self-reported questionnaires to assess the presence and
      features of spontaneous daily pain during one year (1998) were completed by 151
      outpatients with osteoarthritis (OA) (n = 52), rheumatoid arthritis (RA) (n =
      82), and fibromyalgia (FM) (n = 17) and 32 healthy subjects. Data were correlated
      with daily temperature, atmospheric pressure, and relative humidity obtained
      during the same period. Only p values < 0.001 were considered significant.
      RESULTS: Low temperature, high atmospheric pressure, and high humidity were
      significantly correlated with pain in RA (r = -0.30, r = 0.34, r = 0.23,
      respectively; p < 0.001); in OA, pain correlated with low temperature and high
      humidity (r = -0.23, r = 0.24; p < 0.001); in FM, with low temperature and high
      atmospheric pressure (r = -0.255, r = 0.22; p < 0.001) and no correlation was
      found in controls. Patients self-described as being weather sensitive correlated
      only with high humidity (r = 0.45; p < 0.001). There was no better correlation
      with climate variables, except for humidity, 5 days before or after the day of
      the painful episode. CONCLUSION: These results support the belief that weather
      influences rheumatic pain, albeit in different ways depending on the subjacent
      pathology and subjective weather sensitivity. This influence may not depend on
      weather conditions of the previous or following days, indicating that climate
      would not be a pain predictor and vice versa.

PMID- 11838854
TI  - Rheumatologists' adherence to guidelines for misoprostol use in patients at high
      risk for nonsteroidal antiinflammatory drug gastropathy.
AB  - OBJECTIVE: To determine the extent of evidence based practice among
      rheumatologists in the prevention of nonsteroidal antiinflammatory drug (NSAID)
      associated peptic ulcer disease and to seek ways to improve the management of
      high risk NSAID users. METHODS: In March 1996 all 7 rheumatologists from
      Saskatoon participated in a consensus conference to develop local guidelines for
      the prophylaxis of NSAID associated peptic ulcer disease. We performed a
      retrospective chart review for September/October 1995 (baseline) and for
      June/July 1996 (post-consensus guideline) of all patients from Saskatoon
      rheumatologists who were being treated with NSAID for either rheumatoid arthritis
      (RA) or undifferentiated inflammatory polyarthritis (IP). A prospective crossover
      intervention study was performed from January to April 1997 in which 2 subgroups
      of rheumatologists (university or private practice) had a reminder sheet of
      gastrointestinal (GI) bleeding risk assessment placed into the front of each
      patient's chart prior to each office visit. The GI bleeding risk for each patient
      at time of visit was later determined by chart review. The primary outcome was
      the proportion of adherence to guidelines for high risk NSAID users in the
      combined intervention group (reminder sheet) compared to the combined control
      group (no reminder sheet) in the prospective controlled crossover study. RESULTS:
      A total of 484 patients with RA or IP received NSAID during the 4 study periods.
      Of these, 82 patients (16.9%) were at high risk of GI bleed. In 1995, the
      proportion of high risk patients taking misoprostol was 29% for university and
      33% for private practice rheumatologists. The establishment of local consensus
      guidelines in 1996 temporarily increased adherence to guidelines to 43%, but only
      for private practice rheumatologists. During the prospective study, adherence to
      guidelines was significantly greater in the intervention (reminder sheets) group
      compared to the control (no reminder sheets) group (53% vs 15%; p = 0.014).
      CONCLUSION: The simple intervention of reminder sheets for GI bleeding risk
      assessment resulted in a significant increase in rheumatologists' adherence to
      guidelines, although a substantial number of patients remained untreated with
      misoprostol. This study illustrates the difficulty of incorporating new knowledge
      and recommendations into clinical practice. Additional strategies should be
      investigated to more effectively incorporate new knowledge in the practice of
      rheumatology.

PMID- 11838855
TI  - A composite index for total hip arthroplasty in patients with hip osteoarthritis.
AB  - OBJECTIVE: We propose a composite index for considering total hip arthroplasty
      (THA) in hip osteoarthritis (OA). METHODS: We carried out a 3 year longitudinal
      study of patients with painful hip OA from 137 centers. Clinical data were
      collected at baseline and every 3 months; radiographs were taken at entry and
      each year. The decision to have surgery was made by the patient, the
      rheumatologist, and the surgeon, with no reference to outcome measures.
      Statistical analysis included discrete Cox analysis with time dependent
      covariates, on 3 month interval grouped data. The dependent variable was THA
      during the 3 months following the evaluated visit. Time dependent covariates
      collated at each evaluated visit included radiological joint space width (JSW),
      percentage decrease in JSW during the year preceding, patient's global
      assessment. Lequesne index, pain, and nonsteroidal antiinflammatory drug and
      analgesic intake. We compared 2 analyses differing in symptomatic variables
      entered: values obtained at a single time point vs mean values between 2 visits
      at a 3 month interval. Selection of the index was based on the best combination
      of variables to predict occurrence of THA. RESULTS: Of the 508 patients recruited
      for study, 42 were excluded. During the 3 year followup, 75 patients underwent
      THA. Symptomatic, therapeutic, and radiological variables were included in the
      index resulting from the 2 analyses. Based on the selected cutoff, the positive
      and negative predictive values for occurrence of THA in the 2 years following
      were 54.3 and 90.6%, respectively (single point model), and 52.9 and 86.7%,
      respectively (model using mean values of symptomatic variables between 2 visits).
      CONCLUSION: The poor positive predictive value of the composite indices obtained
      in this study suggests that there are other unmeasured factors determining access
      to surgery. On the other hand, the high negative predictive values suggest that
      these composite measures should be used by clinicians to determine which patients
      should not be referred to THA.

PMID- 11838856
TI  - Cytokines and depression in cases with fibromyalgia.
AB  - OBJECTIVE: Fibromyalgia (FM) is a chronic, painful musculoskeletal disorder
      characterized by widespread pain, pressure, hyperalgesia, morning stiffness, and
      an increased incidence of depressive symptoms. The etiology, however, has
      remained elusive. The aim of the present study was to examine the inflammatory
      response system in FM and to investigate the effect of depression level on serum
      cytokines. METHODS: Serum interleukin-1 (IL-I), IL-2 receptor (IL-2r), IL-6, and
      IL-8 and the Hamilton Depression Rating Scale (HDRS) score were determined in 32
      healthy volunteers and in 81 patients with FM, classified according to the
      American College of Rheumatology criteria. RESULTS: In our study, serum IL-1 and
      IL-6 were not statistically significant, but serum IL-8, IL2r, and HDRS score
      were significantly higher in patients with FM than the control group (p < 0.01).
      In addition, in patients with FM, IL-8 was found to be related to pain intensity
      (r = 0.35; p < 0.01). CONCLUSION: IL-8 may play an important role in the
      occurrence of pain in FM.

PMID- 11838857
TI  - Does self-management education benefit all populations with arthritis? A
      randomized controlled trial in a primary care physician network.
AB  - OBJECTIVE: Studies have suggested that the Arthritis Self-Management Program
      (ASMP) course is effective at reducing arthritis pain and health care costs in
      volunteer participants. There have been no reports of trials of the ASMP in the
      context of primary care physicians' practices, where the potential for spreading
      the program may be greatest. We conducted a randomized controlled trial of the
      ASMP course in a large primary care physician network. METHODS: Patients with
      osteoarthritis, rheumatoid arthritis, or fibromyalgia were recruited for the
      study. Subjects in the intervention practices received the 6 week course and
      those in the control practices received only the ASMP book, without course.
      Disability, pain, self-efficacy, mental health, and satisfaction were measured
      using validated instruments at baseline and at 4 months. RESULTS: One hundred
      thirteen patients were recruited for the ASMP course (intervention) and completed
      baseline and 4 month followup questionnaires. Eighty-four percent completed at
      least 4 of 6 classes. Seventy-four patients received the ASMP manual (controls)
      and completed both questionnaires. Patients in the intervention and control
      groups had similar baseline pain (p = 0.94), self-efficacy to control pain (p =
      0.90), mental health (p = 0.10), and vitality scores (p = 0.21), but those in the
      intervention arm had slightly less disability (p = 0.04). At 4 months, there was
      no significant improvement from baseline in any endpoint and no difference
      between patients in the intervention and control groups (all p > 0.2). Patient
      satisfaction with arthritis care and outcomes was no different for intervention
      and control patients (all p > 0.3). All types of health care resource use were
      similar at baseline and followup for both intervention and control groups (all p
      > 0.2). CONCLUSION: While the ASMP course has been found to be effective in other
      patient groups, there were no significant clinical benefits noted at 4 months in
      patients recruited from primary care practices.

PMID- 11838858
TI  - Interferon-gamma:interleukin 4 ratios and associated type 1 cytokine expression
      in juvenile rheumatoid arthritis synovial tissue.
AB  - OBJECTIVE: To compare synovial tissue cytokine mRNA expression between patients
      with juvenile rheumatoid arthritis (JRA) and a heterogeneous group of non
      autoimmune arthropathies (controls) with respect to type 1/type 2 balance.
      METHODS: Thirty-five JRA (average 9.1 years' disease duration) and 13 control
      synovial tissues were studied. As a measure of the type 1/type 2 cytokine balance
      in a subset of the JRA and control tissues, interferon-gamma (IFN-gamma) and
      interleukin 4 (IL-4) mRNA levels were measured by competitive fragment reverse
      transcription-polymerase chain reaction. To quantitate additional cytokines
      relevant to this balance, multiprobe ribonuclease protection assays were employed
      measuring IL-5, IL-10, IL-13, IL-15, IL-18, and IL-12 (p35 and p40 subunits).
      Immunohistochemistry was performed on JRA tissues using antibodies specific for
      IL-15 and IL-18. RESULTS: A higher IFN-gamma:IL-4 ratio (p = 0.034) was found in
      JRA tissues compared to controls. JRA tissues also displayed higher mRNA levels
      of IL-12p35 (p = 0.021), IL-15 (p = 0.002), and IL-18 (p = 0.017), but not IL-4
      and IL-10. IFN-gamma expression in JRA, but not controls, correlated strongly
      with IL-12p35 (r = 0.63) and IL-12p40 (r = 0.73) levels. A subset of IL-15+ and
      IL-18+ cells was detected in JRA synovial tissues, largely within perivascular
      aggregates. CONCLUSION: JRA synovial tissue cytokine expression patterns indicate
      a type 1 bias, even in the later stages of disease. The strong correlation
      between IFN-gamma and IL-12 in JRA suggests a prominent role for IL-12 in
      promoting the type I bias, while IL-15 and IL-18 may also indirectly increase IFN
      gamma expression and further bias the immune response.

PMID- 11838859
TI  - Ethnic differences in risk for pediatric rheumatic illness in a culturally
      diverse population.
AB  - OBJECTIVE: To analyze the differences of occurrence of pediatric rheumatic
      disease among various ethnic groups in a culturally diverse isolated geographic
      area. METHODS: A retrospective study of pediatric rheumatic diseases in a
      multiethnic area during a 6 year period. RESULTS: A group of 922 patients was
      categorized based on predominant ethnicity, and their risk of having acute
      rheumatic fever (ARF), juvenile rheumatoid arthritis (JRA), and systemic lupus
      erythematosus (SLE) was studied. Odds ratios (OR) were computed for each illness
      with Caucasians as the reference group. Results indicated that Polynesians were
      overrepresented among patients with ARF, having elevated OR that were
      significantly different from Caucasians (22.5-120.7, p < 0.0001). For SLE, the
      highest OR were obtained for Samoans, Filipinos, and Japanese. In contrast, for
      JRA, Filipinos and Japanese had OR less than one, and no Samoans were diagnosed
      with JRA, possibly indicating a protective effect against developing JRA.
      CONCLUSION: This unique retrospective study examined the ethnic variations of
      expression of certain rheumatic diseases in an isolated region. Results reveal
      that certain ethnic groups are at risk for ARF and SLE, but are protected against
      JRA. These findings suggest investigating possible immunogenetic similarities and
      differences in these illnesses.

PMID- 11838860
TI  - SAPHO syndrome and transient hemiparesis in a child: coincidence or new
      association?
AB  - We describe a case of synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO
      syndrome) in an 8-year-old boy with an unusual presentation of acute transitory
      hemiparesis. SAPHO syndrome has been reported in association with inflammatory
      bowel diseases, chest complications, and pulmonary involvement. No patient with
      both SAPHO syndrome and neurologic complaints has been previously described.
      Further observations are needed to confirm if SAPHO syndrome and hemiparesis
      represent a coincidence or a new association.

PMID- 11838861
TI  - Delayed relapse of Churg-Strauss syndrome manifesting as colon ulcers with
      mucosal granulomas: 3 cases.
AB  - Churg-Strauss syndrome (CSS) is characterized by small vessel vasculitis and
      extravascular granulomas. The American College of Rheumatology classification
      criteria for CSS include asthma, eosinophili, and clinical manifestation of
      vasculitis. Gastrointestinal (GI) manifestations occur in 30% of patients, but
      are inaugural in only 16%. They denote vasculitis of the stomach and small bowel
      wall, and consist in protean, nonspecific pain. GI involvement is of adverse
      prognostic significance in CSS. Ulcer formation in the GI tract mucosa is a rarer
      manifestation, usually discovered upon laparotomy or autopsy. We describe 3 new
      cases of colonic ulcers in CSS. Unusual features were diagnosis of the ulcers
      during a delayed relapse and presence of eosinophilic granulomas within the
      mucosa.

PMID- 11838862
TI  - Periaortitis heralding Wegener's granulomatosis.
AB  - We describe a 47-year-old man who successively presented atheromatous coronary
      artery disease, cholesterol embolism after angioplasty, periaortitis with
      presence of c-ANCA, and finally typical pulmonary lesions caused by Wegener's
      granulomatosis. This case illustrates the link between atheromatous and
      inflammatory process and emphasizes that periaortitis may be a feature of
      Wegener's granulomatosis.

PMID- 11838863
TI  - Diagnostic relevance of antibodies to serotonin and phospholipids in fibromyalgia
      syndrome.

PMID- 11838864
TI  - Is hypermobility a factor in fibromyalgia?

PMID- 11838865
TI  - Warfarin and azathioprine: clinically significant drug interaction.

PMID- 11838866
TI  - Obesity does not impair rehabilitation outcome in spondyloarthropathy.

PMID- 11838867
TI  - Validation of a German version of the disabilities of arm, shoulder, and hand
      questionnaire (DASH-G).

PMID- 11838868
TI  - Acute inflammation at the site of calcinosis in limited cutaneous scieroderma.

PMID- 11838869
TI  - Gerodontology - what is it and what does it mean to us?

PMID- 11838870
TI  - The oral medicine of tooth wear.
AB  - This review illustrates, through a series of case histories, how oral medicine
      insights aid the diagnosis and management of patients with excessive tooth wear.
      The cases reviewed are drawn from the records of 500 southeast Queensland
      patients referred to the author over a 12 year period. Patients most at risk of
      dental erosion have work and sports dehydration, caffeine addiction, gastro
      oesophageal reflux, asthma, diabetes mellitus, hypertension or other systemic
      diseases or syndromes that predispose to xerostomia. Saliva protects the teeth
      from the extrinsic and intrinsic acids which cause dental erosion. Erosion,
      exacerbated by attrition and abrasion, is the main cause of tooth wear. These
      cases illustrate that teeth, oral mucosa, salivary glands, skin and eyes should
      be examined for evidence of salivary hypofunction and attendant medical
      conditions. Based on comprehensive oral medicine, dietary analyses and advice, it
      would seem patients need self-management plans to deal with incipient chronic
      tooth wear. The alternative is the expensive treatment of pain, occlusal damage
      and pulp death required to repair the effects of acute severe tooth wear.

PMID- 11838871
TI  - Classical and variant Creutzfeldt-Jakob diseases and their potential impact on
      the practice of clinical dentistry in Australia.
AB  - Following recent published evidence regarding the experimental transmission of
      prion diseases via blood transfusion, dental practitioners have expressed their
      concern about the potential impact of these transmissible spongiform
      encephalopathies on dental care provision. This review provides updated
      information on Creutzfeldt-Jakob disease and related disorders and highlights
      their potential significance for the practice of clinical dentistry. The current
      guidelines in Australia relating to infection control and clinical dental
      procedures are discussed together with recommended guidelines and considerations
      from the United Kingdom and the World Health Organization (WHO).

PMID- 11838872
TI  - Pits and fissures: etch resistance in prismless enamel walls.
AB  - BACKGROUND: In a previous study to examine the nature of etching on the walls of
      fissures, there was a consistent result of resistance to deep etching on parts of
      the walls and a zone of lesser etching on part of the walls as evidenced by the
      uptake of stain. The staining had been used to examine the nature of the etch
      pattern. The aims of this study were to define the nature of this etch resistant
      area. METHODS: A sample of 55 teeth, both molars and premolars, were divided into
      three groups. In the first group the wetting of fissures by the etchant was
      examined; the second group tested for the effects of pellicle-cuticle-debris or
      air entrapment on the etching process. The final group looked at alternative
      mechanical treatments of the fissure prior to etching. RESULTS: The specimens
      split along the fissures showed clearly that the etch resistant zone was not due
      to lack of contact with the etchant or the presence of a pellicle-cuticle-debris
      covering, but to the presence of a prismless enamel structure. This study showed
      that this zone inhibited tag development on the fissure walls. CONCLUSIONS: The
      mechanical removal of this prismless layer of enamel within the fissure system
      should result in an improved bonding of a fissure sealant through better tag
      development, in turn leading to a reduction in the failure rate of a sealant used
      to prevent caries.

PMID- 11838873
TI  - Dental erosion: in vitro model of wine assessor's erosion.
AB  - BACKGROUND: Wine makers and assessors frequently experience severe dental
      erosion. The objectives of this study were to develop an in vitro model of dental
      erosion caused by frequent wine contact with teeth, and to use this model to
      assess the effectiveness of a variety of methods which might protect against this
      form of erosion. METHODS: An initial pilot study found that riesling style wine
      was more erosive than champagne style, and both more than claret. Wine tasting
      was simulated by subjecting exposed windows of enamel and root surfaces on 50
      intact, extracted human teeth to 1400 one minute exposures to white wine (ph
      3.2). A variety of dental materials were applied to the exposed windows on groups
      of teeth prior to erosive challenge, to assess their protective ability. RESULTS:
      Protective resin coatings and fluoride varnishes protected both enamel and roots
      against wine induced erosion. A high degree of protection was provided by apf
      gel, with less by naf gel. CONCLUSIONS: It was concluded that dentists may be
      able to help minimise erosion resulting from frequent wine-tasting in their
      patients by the clinical application of one or a combination of these agents at
      times prior to prolonged assessment periods.

PMID- 11838874
TI  - The shelf-life of sodium hypochlorite irrigating solutions.
AB  - BACKGROUND: Sodium hypochlorite (bleach) solutions are widely used as irrigants
      in endodontics. Their tendency to deteriorate is worsened by environmental
      influences which could cause loss of available chlorine content. METHODS: This
      study measured the loss of available chlorine concentration in a range of sodium
      hypochlorite solutions under conditions which mimic clinical usage and storage.
      Domestic bleach, both undiluted and diluted with demineralised water or hard
      water, was tested, along with Milton, for initial concentration of available
      chlorine, and then retested after varying periods and modes of storage to measure
      loss of chlorine concentration. The types of storage were: (1) in closed plastic
      bottles which were opened daily and agitated; (2) in open plastic bottles; (3) in
      syringes exposed to sunlight; (4) in syringes kept in the dark; (5) in open
      stainless steel bowls; (6) in closed stainless steel bowls; and (7) when heated
      to 50 degrees C. Not all solutions were tested under all storage conditions.
      RESULTS: Of the solutions opened daily, undiluted domestic bleach was the most
      stable and Milton was the least stable. Initially, diluted bleach left open
      deteriorated rapidly but deterioration slowed with time. Solutions in syringes
      exposed to sunlight showed the most rapid loss of chlorine content. Heated bleach
      lost nearly 5 per cent of its strength in six hours. Diluted bleach surprisingly,
      increased its chlorine concentration in open bowls probably due to evaporation of
      water. Dilution of bleach with hard tap water did not significantly affect shelf
      life. Preloading of diluted bleach into syringes appears to be a sound technique
      if the syringes are stored away from light. CONCLUSIONS: This study reinforces
      the need for sodium hypochlorite to be stored in closed opaque containers.
      Constant opening of containers appears to cause greater loss in chlorine
      concentration of diluted bleach solutions, perhaps because a lower concentration
      of sodium hydroxide allows the pH to drop more rapidly.

PMID- 11838875
TI  - Opinions of dentists and directors of nursing concerning dental care provision
      for Adelaide nursing homes.
AB  - BACKGROUND: The complex oral health problems of nursing home residents have been
      well documented. However, the influences on residents' oral health status,
      including opinions and experiences of dental professionals and nursing home
      staff, have not yet been adequately investigated. METHODS: The baseline
      questionnaire component of this longitudinal study was mailed to all registered
      dentists practising in Adelaide and Adelaide nursing home directors of nursing
      (DONs). RESULTS: 413 dentists and 97 DONs indicated that Adelaide dentists'
      interest and training in nursing home dentistry was low. Dental service provision
      for nursing home residents was very low and dentists preferred to provide
      treatment at their dental practices. Few dental hygienists were working in
      nursing homes and dental professionals provided little educational assistance for
      nursing home staff. Dentists and DONs held several common and many varying
      perceptions of the problems associated with dental care provision in nursing
      homes. Both identified a group of nursing home environmental constraints and a
      lack of portable dental equipment. DONs further identified a group of resident
      related problems, and dentists a group of dental practice-related problems.
      CONCLUSIONS: These study results provide important information concerning
      problems with nursing home dentistry for dental service providers, educators,
      policy-makers, administrators and nursing home staff.

PMID- 11838876
TI  - Incidence and aetiology of facial injuries resulting from motor vehicle accidents
      in Queensland for a three-year period.
AB  - BACKGROUND: No studies have been reported on the frequency and aetiology of
      facial injuries due to MVAs in Queensland. This study aims to investigate the
      incidence, aetiology, age and sex distribution of facial injuries resulting from
      MVAs for a period of three years. METHOD: Cases were identified from the Motor
      Accident Insurance Commission, Queensland. Information including the type of
      injury sustained, the time, age and role of the patient in the accident were
      recorded and analysed. RESULTS: There was an average maxillofacial injury
      incidence of 4.8/100,000 per year, 53.5 per cent in males and 46.5 per cent in
      females. A peak incidence was found for both sexes aged 18 to 22 years. In males,
      57 per cent of facial injuries occurred in this age group compared to 41 per cent
      in females. CONCLUSIONS: Maxillofacial injuries as a result of MVAs are still
      relatively high regardless of the legislation for compulsory seatbelt use. Recent
      advances in seatbelt systems have the potential to reduce the risk of head and
      face impacts. The airbag is also well established as an effective means of
      preventing serious head and face injury. However, more research is required to
      further reduce the incidence of maxillofacial injuries as a result of MVAs.

PMID- 11838877
TI  - Professional development for dentists: patterns and their implications.
AB  - BACKGROUND: Approaches to models of professional development for dentists
      continue to evolve. This study examined the participation and attitudes of
      dentists in non-formal and informal professional development and continuing
      dental education. METHODS: Two methodologies were utilised: a self-administered
      cross-sectional survey of dentists in Victoria, Australia (conducted October to
      December, 1994), and a review of the records of the Continuing Education Unit of
      the School of Dental Science at The University of Melbourne for 1995 to 1999. For
      the cross-sectional survey, the sampling frame was the register of dentists of
      the Dental Board of Victoria in 1994. RESULTS: From a sample of 616 dentists
      invited to participate, 396 usable questionnaires were returned (response rate,
      66.8 per cent). The valid data indicated that 52.5 per cent of dentists belonged
      to a study group, 66.5 per cent subscribed to at least one dental journal (other
      than the Australian Dental Journal), 88.9 per cent discussed dental matters with
      colleagues regularly, 98.6 per cent personally assessed their own work, 13.3 per
      cent did not attend continuing education courses and 18.1 per cent did not
      complete any courses in the year preceding the survey. Participation patterns in
      continuing education courses were related to socio-demographic characteristics of
      dentists. Some support was apparent for flexible delivery options for
      professional development. CONCLUSIONS: Involvement of dentists in Victoria,
      Australia in professional development activities is high, with complex
      participation patterns. Whether these patterns adequately address their own and
      the community's needs for such activities is debatable. Such issues should impact
      on any regulatory models for professional development for dentists and the
      development and use of alternative continuing education modalities.

PMID- 11838878
TI  - Oral lesions in scurvy.
AB  - Scurvy is the nutritional deficiency state associated with lowered levels of
      ascorbic acid (vitamin C). Lack of ascorbic acid leads to suppression of collagen
      synthesis and the synthesis of defective collagen among other metabolic
      derangements. Weakening of vascular walls results in signs and symptoms mimicking
      other diseases such as bleeding diatheses and deep vein thrombosis. Scurvy is
      rarely encountered in Western countries where there is a broad community
      understanding of the importance of nutritional requirements and where foods
      containing ascorbic acid are readily available. As a result of these factors
      early diagnosis may be hampered where it is not considered in the differential
      diagnosis, and consequently, prolonged suffering of the patient. Scurvy is easily
      treated with high doses of oral ascorbic acid, although recurrences may occur.
      Education of health care providers in recognizing the signs and symptoms of
      scurvy therefore cannot be over emphasized, particularly in societies in which
      nutritional deficiencies are considered uncommon. A case of scurvy presenting
      primarily with oral manifestations is reported here.

PMID- 11838879
TI  - Digital imaging for dentists.
AB  - This review of digital imaging and the technical aspects of radiographic
      equipment manufactured for dentists is designed to provide practical information
      to assist in the decision making process and purchase of radiographic digital
      imaging for clinical use.

PMID- 11838880
TI  - On continuing education.

PMID- 11838881
TI  - The role of tea in human health: an update.
AB  - Tea is an important dietary source of flavanols and flavonols. In vitro and
      animal studies provide strong evidence that tea polyphenols may possess the
      bioactivity to affect the pathogenesis of several chronic diseases, especially
      cardiovascular disease and cancer. However, the results from epidemiological and
      clinical studies of the relationship between tea and health are mixed.
      International correlations do not support this relationship although several,
      better controlled case-referent and cohort studies suggest an association with a
      moderate reduction in the risk of chronic disease. Conflicting results between
      human studies may arise, in part, from confounding by socioeconomic and lifestyle
      factors as well as by inadequate methodology to define tea preparation and
      intake. Clinical trials employing putative intermediary indicators of disease,
      particularly biomarkers of oxidative stress status, suggest tea polyphenols could
      play a role in the pathogenesis of cancer and heart disease.

PMID- 11838882
TI  - Lithium: occurrence, dietary intakes, nutritional essentiality.
AB  - Lithium is found in variable amounts in foods; primary food sources are grains
      and vegetables; in some areas, the drinking water also provides significant
      amounts of the element. Human dietary lithium intakes depend on location and the
      type of foods consumed and vary over a wide range. Traces of lithium were
      detected in human organs and fetal tissues already in the late 19th century,
      leading to early suggestions as to possible specific functions in the organism.
      However, it took another century until evidence for the essentiality of lithium
      became available. In studies conducted from the 1970s to the 1990s, rats and
      goats maintained on low-lithium rations were shown to exhibit higher mortalities
      as well as reproductive and behavioral abnormalities. In humans defined lithium
      deficiency diseases have not been characterized, but low lithium intakes from
      water supplies were associated with increased rates of suicides, homicides and
      the arrest rates for drug use and other crimes. Lithium appears to play an
      especially important role during the early fetal development as evidenced by the
      high lithium contents of the embryo during the early gestational period. The
      biochemical mechanisms of action of lithium appear to be multifactorial and are
      intercorrelated with the functions of several enzymes, hormones and vitamins, as
      well as with growth and transforming factors. The available experimental evidence
      now appears to be sufficient to accept lithium as essential; a provisional RDA
      for a 70 kg adult of 1,000 microg/day is suggested.

PMID- 11838883
TI  - The use of antioxidants in transmissible spongiform encephalopathies: a case
      report.
AB  - BACKGROUND: Transmissible spongiform encephalopathies (TSE), which include
      Creutzfeldt-Jakob disease and new variant Creutzfeldt-Jakob disease, are diseases
      characterized by progressive deterioration in the central nervous system with
      neuronal degeneration, vacuolatization of the neuropil, and gliosis. Little is
      known about the pathogenic mechanisms of infection, and controversy exits around
      the inciting infective agent. It has been shown that an important factor in
      pathogenesis is the immune system. CASE: The reported case points to beneficial
      effects when antioxidant therapies are used in transmissible spongiform
      encephalopathies. The case revealed an early reversal in cognitive decline and
      subsequent improvements in myoclonus, apnea and rigidity. Although death was the
      ultimate outcome, the patient succumbed to the illness over 22 months after the
      onset of symptoms when the early rapid decline predicted demise within a few
      months. CONCLUSION: It is possible that strategies blocking the effect of
      proinflammatory cytokines and the resulting oxidative damage may stem the
      progressive damage to the neuropil that occurs in spongiform encephalopathies.
      Further investigation into the use of antioxidants and other types of agents
      quelling inflammation needs to be undertaken. If antioxidants could be combined
      with treatments for the inciting infective agent, a new direction could be taken
      in the outcome of transmissible spongiform encephalopathies including CJD and
      vCJD.

PMID- 11838884
TI  - Zinc supplementation in oral rehydration solutions: experimental assessment and
      mechanisms of action.
AB  - BACKGROUND: Zinc deficiency is associated with chronic diarrhea. This condition
      is generally linked to an overproduction of nitric oxide (NO), which induces
      secretion and cellular damage as a free radical. Use of oral rehydration
      solutions (ORS) is an important part of diarrhea treatment, especially early in
      infancy and for patients with cholera. The presence of zinc in an ORS could be a
      positive factor in recovery from diarrheal disease. OBJECTIVE: This study was
      undertaken to determine whether zinc added to an ORS could regulate the synthesis
      of NO metabolites in the lumen of zinc deficient rat intestine, acting as a
      gastrointestinal protector and thus accelerating normalization of intestinal
      function and zinc status. METHODS: The effects of zinc on NO metabolism were
      studied in young male rats fed a zinc deficient diet for three weeks to mimic the
      condition of patients with recurrent diarrheal episodes. During the fourth week
      of the zinc deficient feedings, experimental diarrhea was induced using
      cathartics (magnesium citrate plus phenolphthalein) that exacerbate NO
      production. A standard ORS with or without 1 mM zinc was given to the rats for
      the last two days. A control group received a zinc sufficient diet. Rats were
      killed at each stage. Intestinal nitric oxide synthase (NOS) was assayed, cecal
      fluid contents were analyzed for nitrates and nitrites, intestinal histology was
      examined, and activation of nuclear factor NF-kappaB DNA binding activity was
      determined. RESULTS: Rats fed the zinc-deficient diet for three weeks gained less
      weight than rats fed a normal zinc content diet and had a lower plasma zinc than
      controls (51.6 +/- 5.4 [n = 101 vs. 143.6 +/- 7.2 microg/dL [n = 11], p < 0.05).
      Recovery with ORS+Zn resulted in a higher plasma zinc than with the ORS-Zn
      (ORS+Zn: 186.5 +/- 12.2; ORS-Zn: 57.5 +/- 6.6 microg/dL, p < 0.05). The zinc
      deficient diet did not alter mucosal NOS, as compared to the values of rats fed a
      normal diet. However, those animals which received five days of cathartic fluids
      had a small intestinal NOS higher than that of all other groups. Either ORS+Zn or
      ORS-Zn normalized NOS activity, regardless of cathartic treatment. The rats fed
      the zinc deficient diet had generally a higher content of NO metabolites in the
      cecum than rats fed a normal diet. After recovery with either type of ORS, rats
      given the cathartic remained with higher cecal NO metabolite concentrations than
      rats that had no induced diarrhea. After recovery with ORS+Zn, intestinal villi
      showed significant expansion of the lamina propria, an indication of greater
      absorption of fluid, while with ORS-Zn this was not present. Small intestinal
      homogenates of rats recovering with ORS+Zn had a decreased NF-kappaB DNA binding
      activity than tissues from rats consuming ORS-Zn. CONCLUSIONS: The results are
      consistent with the hypothesis that addition of Zn to an ORS may contribute to
      improving the physiologic status of the small intestine and potentially reduce
      the risks of recurrent diarrhea episodes.

PMID- 11838885
TI  - Vitamin profile of 563 gravidas during trimesters of pregnancy.
AB  - OBJECTIVE: Gestation imposes metabolic stress on the mother which heightens as
      pregnancy progresses. The need for quantifying circulating vitamins is important
      for identifying pitfalls in metabolic imbalance and nutritional status. For this
      reason we wanted to analyze blood vitamin concentrations of B12, thiamin, biotin,
      pantothenate, B6, niacin, riboflavin, folate, vitamins A, C, E and total
      carotenes to determine if imbalances occur during the trimesters of pregnancy.
      METHODS: We randomly selected 563 gravidas who volunteered for this study from
      the obstetrical clinic of New Jersey Medical School; 132 were in 1st trimester,
      198 were in 2nd trimester, and 233 were in 3rd trimester. All were healthy,
      taking a good diet and supplemented with vitamins. Blood, from an antecubital
      vein, was analyzed for thiamin, biotin, B12, B6, pantothenate, riboflavin,
      nicotinate, folates, vitamins A, E, C and total carotenes. Gravidas were
      classified as being normovitaminemic, hypervitaminemic or hypovitaminemic
      compared with blood vitamins seen in healthy non-pregnant, non-vitamin
      supplemented women. RESULT: Hypervitaminemic levels of folate, biotin,
      pantothenate and riboflavin were found during any trimester of pregnancy due to
      vitamin supplementation. Despite the vitamin supplementation, a high percent of
      vitamin A, B6, niacin. thiamin and B 12 hypovitaminemia was noted during
      pregnancy trimesters. An especially high percentage of niacin deficiency was seen
      during the 1st trimester; it worsened in later trimesters; B12 deficits increased
      during the late trimesters. Combination deficits of niacin, thiamin, vitamins A,
      B6, B12 were noted in each of the trimesters. CONCLUSIONS: Despite vitamin
      supplementation, a vitamin profile of pregnancy indicates that vitamin deficits
      exist during the trimesters. Also, combination hypovitaminemias of deficient
      vitamins were noted; this indicates that a vitamin deficit during pregnancy does
      not occur in isolation.

PMID- 11838886
TI  - Effect of low-fat and/or low-energy diets on anthropometric measures in
      participants of the women's diet study.
AB  - OBJECTIVE: To compare the effects of low-fat, low-energy and combination low
      fat/low-energy intervention on changes in six anthropometric measures in
      Caucasian and African-American free-living women. METHODS: The effects of dietary
      counseling strategies for fat and/or energy reduction were examined on
      anthropometric measures in 86 pre-menopausal women, average BMI of 28 kg/m2, who
      participated in a 12-week intervention trial called the Women's Diet Study. The
      dietary goals were 15% of energy from fat and/or 25% reduction in energy intake,
      relative to reported baseline intake, using a 2 x 2 factorial design. Analysis of
      covariance models were constructed to evaluate changes in anthropometric measures
      over the 12 weeks of study. RESULTS: The biggest difference by race was in women
      who were relatively heavier at baseline, in which case African-American women
      lost significantly less weight but decreased their waist:hip ratio to a
      significantly greater extent than Caucasian women. With regard to the effects of
      diet arm, weight loss varied depending on baseline weight, and in women with
      higher baseline weights, the combination low-fat/low-energy diet resulted in the
      most weight loss (6.7 kg, p < 0.05). Decreases in the other anthropometric
      measures at week 12 were more uniform across diet arms and did not depend on
      baseline values. After controlling for previous weight history and race, the
      decreases in BMI, percent body fat and waist circumference after 12 weeks were
      statistically equivalent with the low-fat, low-energy or combination low-fat/low
      energy diets. The relatively greater decreases in percent body fat and waist
      circumference with the combination diet versus the low-fat or low-energy diets
      were not statistically significant. CONCLUSION: The low-fat, low-energy and
      combination diets all resulted in similar and statistically significant decreases
      in BMI, percent body fat and waist circumference over 12 weeks of intervention.
      The extent of weight loss, however, varied depending on baseline weight, and the
      combination diet was the only intervention to result in significant weight loss
      for women who were heavier at baseline. This indicates that, although there may
      be an advantage for reducing dietary fat in initially heavier women, any of these
      counseling strategies could be effective for improving anthropometric predictors
      of health risks associated with overweight status. This is useful since
      flexibility in dietary choices may facilitate adherence to dietary counseling in
      some individuals.

PMID- 11838887
TI  - Dietary calcium intake in lactose maldigesting intolerant and tolerant African
      American women.
AB  - BACKGROUND: The relationship between lactose maldigestion, lactose intolerance,
      and calcium intake in premenopausal African American women is unknown. OBJECTIVE:
      To determine how intolerance of lactose and dairy products affects intake of
      calcium in lactose maldigesting premenopausal African American women. DESIGN:
      Dietary intake of calcium was assessed in 50 premenopausal lactose maldigesting
      African American women as determined by the breath hydrogen test. Twenty-six
      women were lactose intolerant and 24 were lactose tolerant by self-reports.
      RESULTS: The average intake of calcium in lactose maldigesting and intolerant
      women was significantly lower than in lactose tolerant women (388 +/- 150 mg/day
      vs. 763 +/- 333 mg/day, p < 0.0001, t test). Neither group reached the newly
      established Dietary Reference Intake (DRI) for calcium (1,000 mg/day). Major
      source of dietary calcium in lactose tolerant women were milk and dairy products
      (45%), and mixed foods containing calcium from non-dairy sources (30%). In
      lactose intolerant women, 46% of calcium was from mixed foods and only 12% was
      from milk and dairy products. Lactose intolerant women had higher body mass index
      (BMI) than lactose tolerant women (p = 0.008, t test), and calcium intake was
      negatively associated with BMI (R2 = 0.470). CONCLUSIONS: In African American
      premenopausal women, lactose tolerance facilitates the dietary intake of calcium
      when compared with their lactose intolerant counterparts. Low calcium intake is
      associated with higher BMI.

PMID- 11838888
TI  - Postprandial thermogenesis is increased 100% on a high-protein, low-fat diet
      versus a high-carbohydrate, low-fat diet in healthy, young women.
AB  - OBJECTIVE: The recent literature suggests that high-protein, low-fat diets
      promote a greater degree of weight loss compared to high-carbohydrate, low-fat
      diets, but the mechanism of this enhanced weight loss is unclear. This study
      compared the acute, energy-cost of meal-induced thermogenesis on a high-protein,
      low-fat diet versus a high-carbohydrate, low-fat diet. METHODS: Ten healthy,
      normal weight, non-smoking female volunteers aged 19-22 years were recruited from
      a campus population. Using a randomized, cross-over design, subjects consumed the
      high-protein and the high-carbohydrate diets for one day each, and testing was
      separated by a 28- or 56-day interval. Control diets were consumed for two days
      prior to each test day. On test day, the resting energy expenditure, the non
      protein respiratory quotient and body temperature were measured following a 10
      hour fast and at 2.5-hour post breakfast, lunch and dinner. Fasting blood samples
      were collected test day and the next morning, and complete 24-hour urine samples
      were collected the day of testing. RESULTS: Postprandial thermogenesis at 2.5
      hours post-meal averaged about twofold higher on the high protein diet versus the
      high carbohydrate diet, and differences were significant after the breakfast and
      the dinner meals (p < 0.05). Body temperature was slightly higher on the high
      protein diet (p = 0.08 after the dinner meal). Changes in the respiratory
      quotient post-meals did not differ by diet, and there was no difference in 24
      hour glomerular filtration rates by diet. Nitrogen balance was significantly
      greater on the high-protein diet compared to the high-carbohydrate diet (7.6 +/-
      0.9 and -0.4 +/- 0.5 gN/day, p < 0.05), and at 24-hour post-intervention, fasting
      plasma urea nitrogen concentrations were raised on the high protein diet versus
      the high-carbohydrate diet (13.9 +/- 0.9 and 11.2 +/- 1.0 mg/dL respectively, p <
      0.05). CONCLUSIONS: These data indicate an added energy-cost associated with high
      protein, low-fat diets and may help explain the efficacy of such diets for weight
      loss.

PMID- 11838890
TI  - On the potential value and limitations of emphasis change and other exploration
      enhancing training methods.
AB  - Two experiments are presented that examine the efficiency of training methods
      that force trainees to explore the possible strategy space. Both experiments used
      a 2-dimensional search task. Experiment 1 studies a method that enforces
      exploration by preventing repetitions within short sequences. It shows that the
      effect of this "enhanced exploration" method in the abstract setting is similar
      to the effect of "emphasis change" training (see D. Gopher, 1993) in high
      cognitive workload tasks. This finding appeared only in strategic spaces where
      intuitive exploration converges to a local optimum. Experiment 2 compares the
      effect of exploration enhancement with the effect of guided instruction. The
      results of the experiments, which are captured well by a generalization of I.
      Erev and D. A. Gopher's (1999) model of the conditions for the success of
      emphasis change training, shed light on the limitations and potential of
      exploration-enhancing training methods.

PMID- 11838889
TI  - "Healthy-start": outcome of an intervention to promote a heart healthy diet in
      preschool children.
AB  - OBJECTIVE: We evaluated the effects of a preschool nutrition education and food
      service intervention "Healthy Start," on two-to-five-year-old children in nine
      Head Start Centers in upstate NY. The primary objective was to reduce the
      saturated fat (sat-fat) content of preschool meals to <10% daily energy (E) and
      to reduce consumption of sat-fat by preschoolers to <10% E. METHODS: Six centers
      were assigned to the food service intervention and three to control condition.
      Food service intervention included training workshops for cooks and monthly site
      visits to review progress towards goals. Child dietary intake at preschool was
      assessed by direct observation and plate waste measurement. Dietary intake at
      home was assessed by parental food record and telephone interviews. Dietary data
      were collected each Fall/Spring over two years, including five days of menus and
      recipes from each center. Dietary data were analyzed with the Minnesota NDS
      software. RESULTS: Consumption of saturated fat from school meals decreased
      significantly from 1.0%E to 10.4%E after one year of intervention and to 8.0%E
      after the second year, compared with an increase of 10.2% to 13.0% to 11.4%E,
      respectively, for control schools (p < 0.001). Total caloric intake was
      adequately maintained for both groups. Analysis of preschool menus and recipes
      over the two-year period of intervention showed a significant decrease in sat-fat
      content in intervention preschools (from 12.5 at baseline to 8.0%E compared with
      a change of 12.1%E to >11.6%E in control preschools (p < 0.001)). Total fat
      content of menus also decreased significantly in intervention schools (31.0% to
      >25.0%E) compared with controls (29.9% to >28.4%E). CONCLUSIONS: The Healthy
      Start food service intervention was effective in reducing the fat and saturated
      fat content of preschool meals and reducing children's consumption of saturated
      fat at preschool without compromising energy intake or intake of essential
      nutrients. These goals are consistent with current U.S Dietary Guidelines for
      children older than two years of age.

PMID- 11838891
TI  - Manual and virtual rotation of a three-dimensional object.
AB  - An orientation-matching task, based on a mental rotation paradigm, was used to
      investigate how participants manually rotated a Shepard-Metzler object in the
      real world and in an immersive virtual environment (VE). Participants performed
      manual rotation more quickly and efficiently than virtual rotation, but the
      general pattern of results was similar for both. The rate of rotation increased
      with the starting angle between the stimuli meaning that, in common with many
      motor tasks, an amplitude-based relationship such as P. M. Fitts' (1954) law is
      applicable. When rotation was inefficient (i.e., not by the shortest path), it
      was often because participants incorrectly perceived the orientation of one of
      the objects, and this happened more in the VE than in the real world. Thus, VEs
      allow objects to be manipulated naturally to a limited extent, indicating the
      need for timing-scale factors to be used for applications such as method-time
      motion studies of manufacturing operations.

PMID- 11838892
TI  - Interleaving reading and acting while following procedural instructions.
AB  - Memory for an interactive procedure acquired from written instructions is
      improved if the procedure can be carried out while the instructions are being
      read. The size of the read-act cycle was manipulated in Experiments 1 and 2 by
      comparing chunked instruction-following, in which 3 or 4 steps are read then
      performed with single-step conditions. In both experiments, enforced chunking
      improved subsequent unaided performance of the procedure. In Experiment 3,
      participants were allowed to manage the interleaving of reading and acting. The
      imposition of a small behavioral cost (a single mouse point-and-click operation)
      on the switch between instructions and device encouraged more chunking and better
      subsequent test performance. The authors concluded that the interleaving of
      reading and acting is an important practical concern in the design of interactive
      procedures and that more effective chunk-based strategies can quite readily be
      encouraged.

PMID- 11838893
TI  - Mental models and logical reasoning problems in the GRE.
AB  - The Graduate Record Examination (GRE) contains a class of complex reasoning tests
      known as logical reasoning problems. These problems are demanding for human
      reasoners and beyond the competence of any existing computer program. This
      article applies the mental model theory of reasoning to the analysis of these
      problems. It predicts 3 main causes of difficulty, which were corroborated by the
      results of 4 experiments: the nature of the logical task (Experiment 1), the set
      of foils (Experiment 2), and the nature of the conclusions (Experiments 3 and 4).
      This article shows how these factors can be applied to the design of new
      problems.

PMID- 11838894
TI  - Expertise and estimating what other people know: the influence of professional
      experience and type of knowledge.
AB  - There is ample evidence that estimations of what other people know are often
      biased in the direction of one's own knowledge. Yet, it is still unclear if this
      bias is influenced by expertise. In Study 1, computer experts estimated the
      distribution of Internet concepts and general knowledge concepts among students.
      These estimations were compared with norm values and with estimations obtained
      from a sample of laypersons. Laypersons showed a stronger bias than experts.
      Study 2 revealed that knowledge estimations can be influenced by labeling
      knowledge items as specialist knowledge. The results are suggestive of ways in
      which communication between experts and laypersons could be enhanced. Especially
      in asynchronous communication situations, as for example in the use of e-mail
      based hot lines, if experts are to communicate effectively, they must make
      accurate assumptions about laypersons' knowledge of the topic.

PMID- 11838895
TI  - Judging the accuracy of children's recall: a statement-level analysis.
AB  - Three experiments were conducted to examine fact finders' judgments of children's
      answers to cued recall questions about a recent dental visit. Participants
      performed better than chance at judging the correctness of the children's answers
      in all 3 experiments, and judgment accuracy was consistently better when the
      children's answers were correct. Judgment performance did not decline when
      confidence information was removed, and when all confidence information was
      removed, the best performance was obtained by parents and by professionals who
      work with children. The findings of these experiments provide support for the use
      of written transcripts in presentations of child testimony and highlight the
      importance of child- and event-related knowledge in judgments of children's
      testimony.

PMID- 11838896
TI  - Paramyxovirus accessory proteins as interferon antagonists.
AB  - A new role of the Paramyxovirus accessory proteins has been uncovered. The P gene
      of the subfamily Paramyxovirinae encodes accessory proteins including the V
      and/or C protein by means of pseudotemplated nucleotide addition (RNA editing) or
      by overlapping open reading frame. The Respirovirus (Sendai virus and human
      parainfluenza virus (hPIV)3) and Rubulavirus (simian virus (SV)5, SV41, mumps
      virus and hPIV2) circumvent the interferon (IFN) response by inhibiting IFN
      signaling. The responsible genes were mapped to the C gene for SeV and the V gene
      for rubulaviruses. On the other hand, wild type measles viruses isolated from
      clinical specimens suppress production of IFN, although responsible viral factors
      remain to be identified. Both human and bovine respiratory syncytial viruses
      (RSVs) counteract the antiviral effect of IFN with inhibiting neither IFN
      signaling nor IFN production. Bovine RSV NS1 and NS2 proteins cooperatively
      antagonize the antiviral effect of IFN. Studies on the molecular mechanism by
      which viruses circumvent the host IFN response will not only illustrate co
      evolution of virus strategies of immune evasion but also provide basic
      information useful for engineering novel antiviral drugs as well as recombinant
      live vaccine.

PMID- 11838897
TI  - Immunological properties of trehalose dimycolate (cord factor) and other mycolic
      acid-containing glycolipids--a review.
AB  - Mycolic acids are characteristic fatty acids of Mycobacteria and are responsible
      for the wax-like consistence of these microorganisms. Decades of research
      revealed that mycolic acid-containing glycolipids, in particular trehalose-6,6'
      dimycolate (TDM, cord factor) as their best-studied representative, exert a
      number of immunomodifying effects. They are able to stimulate innate, early
      adaptive and both humoral and cellular adaptive immunity. Most functions can be
      associated with their ability to induce a wide range of chemokines (MCP-1, MIP
      1alpha, IL-8) and cytokines (e.g., IL-12, IFN-gamma, TNF-alpha, IL-4, IL-6, IL
      10). This review tries to link well-known properties of mycolic acid-containing
      glycolipids, e.g., stimulation of cellular and humoral immunity, granuloma
      formation and anti-tumor activity, with recent findings in molecular immunology
      and to give an outlook on potential practical applications.

PMID- 11838898
TI  - Changes in the cell structure of Flavobacterium psychrophilum with length of
      culture.
AB  - Flavobacterium psychrophilum, the pathogen of bacterial cold-water disease,
      causes serious problems in ayu Plecoglossus altivelis culture. This study
      investigated the effect of the culture period of F. psychrophilum and on the
      structure of its cells. From the SDS-PAGE of total proteins of cellular
      components, much difference was found between the 36 hr culture and the 48 and 72
      hr cultures. A SEM observation of the cells showed many fragments, especially on
      the cell surface of the 36 hr culture. These fragments consisted of an outer
      membrane, seen by TEM observation, and may contain substances causing the
      virulence. Specific proteins observed by the SDS-PAGE and fragments in the 36 hr
      culture may be related to the virulence of F. psychrophilum.

PMID- 11838899
TI  - Bacterial population in Russian space station "Mir".
AB  - We had the opportunity to investigate the bacterial population in air samples,
      condensation water, and inner wall swabs from the Russian space station Mir. From
      the first and second air samples during the mission, 29 and 7 bacterial colonies
      were collected, respectively. The values were equivalent to 16.8 and 4.0 cfu/100
      liter air, respectively. Condensation water was collected from three different
      sites. The total viable bacterial counts were 2.1 x 10(6), 5.2 x 10(2), and 3.0 x
      10(1) cfu/ml. The phylogenetic position of each isolate was determined by total
      16S rDNA sequencing. Bacteria from air samples were mainly Gram-positive (35/36
      colonies), and staphylococci occupied dominant specifically (23/36 colonies). On
      the other hand, Gram-negative bacteria were mainly isolated from condensation
      water samples. Most strains were thought to be opportunistic pathogens or
      environmental bacteria (such as those that inhabit soil, water, or air) found on
      earth. However, 6 of 23 isolates were suspected to be new species according to
      phylogenetic analysis and quantitative DNA-DNA hybridization data. The isolation
      of the other levels 3 and 2 bacteria, using specific selective media, was
      unsuccessful because all samples were heavily contaminated with fungi. To
      overcome this situation, PCR methods were applied to survey most levels 3 and 2
      pathogenic bacteria in the condensation water samples. Up to 380 different
      primers for bacterial pathogens were used in this study. Only Mycobacterium avium
      16S DNA sequences, however, could be amplified from the three water samples. The
      average bacteria count was estimated to be about 10(4) organisms/ml water.

PMID- 11838900
TI  - Effects of mutation in hepatitis C virus nonstructural protein 5A on interferon
      resistance mediated by inhibition of PKR kinase activity in mammalian cells.
AB  - The IFN-induced double-stranded RNA (dsRNA)-activated protein kinase PKR is one
      of the key molecules in the antiviral effects of IFN. To clarify the effects of
      hepatitis C virus nonstructural protein 5A (NS5A) on antiviral activity of IFN,
      in particular on PKR kinase activity, in mammalian cells, we established
      inducible NS5A-expressing cell lines derived from human osteosarcoma (Saos-2).
      The cells expressing NS5A derived from an IFN-resistant clone (NS5A-lb) that
      interacted with endogenous PKR in vitro, showed a suppressive effect on IFN
      function as determined by interference with vesicular stomatitis virus (VSV)
      infection, whereas NS5A (NS5A-2a) from an IFN-sensitive clone did not block the
      antiviral effect of IFN. A mutant with deletion of the IFN sensitivity
      determining region (ISDR) in NS5A-1b (NS5A-AISDR) also interacted with PKR and
      suppressed its activity in vitro. However, neither NS5A-2a nor the C-terminal
      truncated mutant of NS5A-1b (NS5A-deltaC) blocked PKR activity. These
      observations confirmed the previous report that the inhibitory effect of NS5A on
      IFN activity is mediated at least in part by the repression of PKR. In addition,
      we showed that IFN sensitivity was determined not only by the ISDR but that the
      involvement of the C-terminal region of NS5A-1b is important for the suppression
      of PKR activity.

PMID- 11838902
TI  - Ultrastructural features of Borrelia garinii in naturally infected voles,
      Clethrionomys rufocanus, with special reference to the relationship with
      peripheral nerves.
AB  - The ultrastructural features of Borrelia garinii found in the ear tissues of the
      vole, Clethrionomys rufocanus, are described. The spirochetes were observed in
      the interstitium of connective tissue or in contact with fibroblasts and were
      occasionally situated in the endoneurium of the peripheral nerves. The
      spirochetes did not injure or enter into the fibroblasts or Schwann cells. The
      cytotoxicity and migration of the spirochetes are also discussed.

PMID- 11838901
TI  - Crossreactivity of SLE autoantibodies with 70 kDa heat shock proteins of
      Mycobacterium tuberculosis.
AB  - Heat shock proteins (hsp) may be involved in the initiation and perpetuation of
      autoimmune diseases. In order to investigate the possible role of hsp and other
      intracellular proteins of Mycobacterium tuberculosis in the autoantibody
      production in SLE, the immuno-crossreactivity of SLE autoantibodies with
      Mycobacterium tuberculosis sonic extract and hsp-70 kDa was investigated. These
      proteins showed significant binding with Protein A-Sepharose isolated SLE IgG.
      Western blotting of hsp-70 with SLE IgG showed strong recognition, suggesting
      possible involvement of hsp and other intracellular proteins of Mycobacterium
      tuberculosis in the autoantibody induction in SLE.

PMID- 11838903
TI  - Characterization of mumps virus isolated in saitama prefecture, Japan, by
      sequence analysis of the SH gene.
AB  - Mumps virus (MuV) strains isolated from cerebrospinal fluid and throat swabs from
      patients in Saitama Prefecture and Tokyo, Japan, from 1997 to 2000 were examined
      by analyzing the SH gene nucleotide sequence (316-nt). Eighteen of the 20 strains
      studied were divided into three genotypes, recognized as B, G, and H in previous
      reports. Two genotypes (G and H) are believed to be new in Japan. Two of the 20
      strains belonged to none of the previously reported genotypes (A-I), but were
      closely related to two known strains, MP94-H and Loug1/UK97. We propose that the
      two strains identified in this study together with the previously reported
      strains, MP94-H and Loug1/UK97, form a new genotype, designated J, based on the
      divergence of the SH gene nucleotide sequences between these four strains and
      other strains reported (genotypes A-I). Our results also suggest that more than
      two genotypes circulated in Saitama Prefecture from 1997 to 1999, but only one,
      genotype G, was in evidence in 2000. Genotype B was earlier reported as the
      predominant strain in Japan, but it became undetectable by the year 2000. These
      results provide important epidemiological data on mumps in Japan.

PMID- 11838904
TI  - Common cell-surface antigens functioning in self-recognition reactions by both
      somatic cells and gametes in the solitary ascidian Halocynthia roretzi.
AB  - The "contact reaction" is an extremely rapid allogeneic cytotoxic reaction (ACR)
      mediated by hemocytes in the solitary ascidian Halocynthia roretzi. It has been
      proposed that regulation of the alloreactivity of hemocytes may be involved in
      preference for fertilization or self-sterility in this species. To identify the
      receptors and target ligands involved both in self-recognition by somatic cells
      and self-discrimination by gametes, we produced monoclonal antibodies (mAbs) that
      inhibit the ACR mediated by hemocytes and tested their effects on fertilization.
      Six different mAbs that inhibit the ACR were prepared and categorized into three
      groups. Although all three mAbs seemed to have the same ability to inhibit the
      ACR, almost constant and statistically significant inhibition (CRB1.1) and
      infrequent but significant inhibition (CRB2.1, and CRB3.1) of the ACR were
      observed in the same pairs of animals. Pretreatment of the unfertilized eggs with
      CRB1.1, CRB2.1, and CRB3.1, resulted in the constant and statistically
      significant inhibition, infrequent but significant inhibition, and no inhibition,
      respectively, of fertilization. Antigens recognized by CRB1.1 (CRB1.1 antigens)
      were detected on the cell surface of all types of hemocytes and on the vitelline
      coat and follicle cells of unfertilized eggs. CRB2.1 and CRB3.1 antigens were
      detected on the surface of certain types of hemocytes and follicle cells, but not
      on the vitelline coat. CRB mAbs were directed against different epitopes in the N
      linked glycan on glycoproteins. These common carbohydrate antigens on somatic
      cells and gametes may function in some recognition processes in ACR and
      fertilization in H. roretzi.

PMID- 11838905
TI  - Common genetic and environmental vulnerability for alcohol and tobacco use in a
      volunteer sample of older female twins.
AB  - OBJECTIVE: A growing body of literature supports a shared genetic vulnerability
      underlying the use of alcohol and tobacco. We report patterns of genetic and
      environmental correlations for alcohol and tobacco use in a volunteer sample of
      older, white, female twins using three different levels of severity for alcohol
      use and smoking. METHOD: A community-based sample of 1,926 female twins aged 50
      to 96 was recruited through advertisements in a newsletter of the American
      Association of Retired Persons. Subjects were asked to rate alcohol and tobacco
      use over their lifetimes. Three levels of severity for alcohol use and smoking
      were coded: ever drank, weekly drinking, problem drinking; ever smoked, daily
      smoking of one-half pack or more, daily smoking of at least one pack or more.
      Twin correlations for alcohol and tobacco use measures were fit using a
      structural equation-modeling package (Mx). RESULTS: There were significant
      genetic correlations between problem drinking and ever smoking and using at least
      one-half pack per day. For problem drinking/ever smoking, R = 1.0 (95% CI: 0.32
      1.0); for problem drinking/smoking at least one-half pack/day, R = 1.0 (95% CI:
      0.43-1.0). CONCLUSIONS: The shared genetic influence on alcohol use and smoking
      in women is clearest for those subjects with the highest severity of alcohol use
      and problem drinking.

PMID- 11838906
TI  - Clomipramine increases the striatal concentrations of dopamine and homovanillic
      acid in rats chronically consuming alcohol.
AB  - OBJECTIVE: There have been many studies on the relationships between the
      dopaminergic system, alcoholism and antidepressant drugs; the information,
      however, is controversial. The purpose of this study was to examine the effect of
      clomipramine (CMI), a tricyclic antidepressant, on the striatal concentration of
      dopamine (DA) and homovanillic acid (HVA), and their turnover, in a rat model of
      chronic alcohol ingestion. METHOD: After 10 months of exposure to either water
      (expW) or alcohol (expA), female Wistar rats (N = 60) were randomly assigned to
      one of the following six groups: (1) (expW) control group (C), normal diet; (2)
      (expA) alcohol administration group (A), drinking water was replaced by
      commercial brandy that was 38% ethanol; (3) (expW) clomipramine group (CMI),
      received intraperitoneal injections over 4 months; (4) (expA) alcohol
      administration + clomipramine group (ACMI); (5) (expA) alcohol abstinence group
      (AA); and (6) (expA) alcohol abstinence + clomipramine group (AACMI). Each group
      consisted of 10 animals. RESULTS: Chronic alcohol intake decreased striatal
      dopamine concentration (p < .001), whereas clomipramine administration produced a
      significant increase (p < .001) when administered in both control rats and rats
      exposed to long-term alcohol administration. The increase in the ACMI group was
      significantly different (p < .001) when it was compared with the CMI group. In
      the AA and AACMI groups, a significant decrease of striatal dopamine was observed
      (p < .001). During long-term alcohol administration, homovanillic acid decreased
      (p < .005). HVA/DA ratio increased in AA and AACMI groups (p < .001).
      CONCLUSIONS: These findings show that clomipramine produces favorable changes in
      dopaminergic systems altered by chronic alcohol administration. Results also
      provide evidence to support further prospective studies of potential therapeutic
      effects of antidepressant drugs in alcoholism.

PMID- 11838907
TI  - Effects of resveratrol, a flavinoid found in red wine, on infarct size in an
      experimental model of ischemia/reperfusion.
AB  - OBJECTIVE: Resveratrol is a potent anti-inflammatory and anti-oxidant flavinoid
      found in red wine. Resveratrol has been shown to improve ventricular function and
      decrease lactic dehydrogenase release after ischemia in rats. The aim of this
      study was to test whether resveratrol could provide direct cardioprotection to
      myocytes during acute myocardial infarction. METHOD: Anesthetized, open-chest
      rabbits (N= 24) were subjected to 30 minute coronary artery occlusion followed by
      3 hr reperfusion. Before the onset of ischemia (15 minutes), the rabbits were
      randomly assigned (n = 8 in each group) to either high-dose (1.5 mg/kg)
      resveratrol, low-dose (0.15 mg/kg) resveratrol or ethanol vehicle, and the
      effects on infarct size and regional myocardial blood flow (RMBF) were tested.
      RESULTS: Hemodynamic parameters and size of ischemic risk region (29% to 35% of
      the left ventricle) were similar in all groups. Infarct size, expressed as a mean
      (SEM) percentage of the risk region, was 46% (5%) of the risk region in controls,
      46% (7%) in the low-dose group and 54% (3%) in the high-dose group (p = .53).
      Thus, treatment with resveratrol had no effect on infarct size at either dose.
      There were no differences in RMBF in the risk zone or in nonischemic tissue,
      during either occlusion or reperfusion. CONCLUSIONS: In this intact model of
      ischemia and reperfusion, resveratrol fails to provide cardioprotection. The
      mechanism of other beneficial effects (e.g., improvement of function) that are
      observed with resveratrol probably do not result from increased RMBF or a
      reduction in myocardial necrosis.

PMID- 11838908
TI  - Substance P and neurokinin levels are decreased in the cortex and hypothalamus of
      alcohol-preferring (P) rats.
AB  - OBJECTIVE: Central tachykinin levels (i.e., substance P [SP], neurokinin A [NKA],
      neurokinin B [NKB] and neurokinin K [NKK]) have been reported to fluctuate in
      association with stress and anxiety. Ethanol can also modulate stress and
      anxiety. Further, ethanol intake can change as a result of stress and anxiety.
      This suggests possible interactions between ethanol and central tachykinins,
      i.e., changing tachykinin levels could influence ethanol intake and vice versa.
      However, to date few studies have assessed the potential relationship between
      tachykinin levels in the brain and ethanol preference. The present study was
      designed to determine if rodent lines selectively bred for differences in alcohol
      preference (i.e., alcohol-preferring [P] and non-preferring [NP] rats) have
      different tachykinin levels in the brain. METHOD: Tissue samples from the brains
      of ethanol-naive P and NP rats were collected from the frontal cortex, caudate,
      hippocampus, amygdala and hypothalamus. Using radioimmuno assays, concentrations
      of SP-like immunoreactivity (SP-LI) and neurokinin-like immunoreactivity (NK-LI,
      i.e., neurokinin A, B and K) in P and NP rats were determined. RESULTS: In P
      rats, SP-LI was significantly lower in the frontal cortex (F= 12.80, 1/26 df, p =
      .001) while NK-LI was significantly lower in the frontal cortex (F = 7.36, 1/26
      df, p = .012) and hypothalamus (F = 5.32, 1/26 df, p = .029) compared with NP
      rats. CONCLUSIONS: These data indicate that endogenous SP and neurokinin levels
      are reduced in discrete brain regions of P rats compared with NP rats. These
      decreases may be associated with decreased serotonergic innervation of these
      brain regions in P rats compared with NP rats.

PMID- 11838909
TI  - Alcohol consumption and academic performance in a population of Spanish high
      school students.
AB  - OBJECTIVE: The present study was designed to identify patterns of alcohol
      consumption among Spanish high school students and describe the relationship
      between alcohol intake and school performance. METHOD: The sample population
      consisted of students, aged 14 to 19 years, who were attending high school during
      the academic year 1994-95 in the city of Granada in southern Spain. We studied
      1,602 (861 female) students (alpha error - 0.05, sampling error = 5%), using a
      self-administered questionnaire that contained items about individual and family
      demographics, quantity and frequency of alcohol consumption, and school
      performance. Total alcohol consumption was recorded as grams (g) of alcohol per
      week and per day for three categories of alcoholic drinks: wine, beer and
      distilled spirits. RESULTS: The percentage of nondrinkers was 21.05% for male
      adolescents and 28.56% for female adolescents. The mean amount of alcohol
      consumed per week was larger in male than in female students (F= 18.36, l/l,594
      df, p < .001) and distilled spirits accounted for the largest proportion of
      alcohol consumed. No significant differences in drinking patterns were found
      between students at public and private schools. The risk of academic failure
      increased considerably when more than 150 g of alcohol were consumed per week
      (OR: 2.91; 95% CI: 1.94-4.43). CONCLUSIONS: Although we cannot draw any
      conclusions about the causes of the association between academic failure and
      teenage drinking, our results do show that the risk of failing increases together
      with alcohol intake. However, it should be noted that academic achievement is
      also influenced by many factors other than alcohol consumption.

PMID- 11838910
TI  - Drinking in adulthood: similarities and differences in effects of adult roles for
      Hispanic ethnic groups and Anglos.
AB  - OBJECTIVE: This study examines whether the adult social roles perspective. an
      approach that explains drinking behaviors for Anglos, similarly affects alcohol
      use by Cubans, Mexican Americans, Puerto Ricans and Other Hispanics (Central and
      South Americans). METHOD: The 1993 National Household Survey on Drug Abuse, a
      national probability sample of the household population in the United States, is
      used. The sample utilized here (N= 13,822; 56.2% female) consisted of 9,388
      Anglos, 611 Cubans, 2,459 Mexican Americans, 611 Puerto Ricans and 753
      Central/South Americans age 18 and older. The outcome measures include past-year
      drinking, and for drinkers, heavy drinking and alcohol-related problems. Logistic
      regression analyses are conducted using Stata. RESULTS: The results show that
      there are some ethnic differences in the effects of the adult social roles. Of
      particular importance is the finding that being married has anomalous effects for
      Cubans (heavy drinking), Mexican Americans (problems) and Other Hispanics
      (problems) compared with Anglos and the other Hispanic ethnic groups.
      CONCLUSIONS: The adult social roles perspective has some utility for explaining
      Hispanic drinking patterns. Future research should consider not only traditional
      predictors of drinking but also such socio-cultural factors as acculturation and
      familism, to better understand adult alcohol use by members of Hispanic ethnic
      groups.

PMID- 11838911
TI  - DUI-arrest characteristics among white and Mexican-American DUI offenders
      mandated for treatment.
AB  - OBJECTIVE: To report cross-ethnic differences among white and Mexican-American
      DUI offenders on the characteristics of an arrest (index) that brought subjects
      to treatment. METHOD: Subjects are 250 (223 male) whites and 249 (187 male)
      Mexican Americans consecutively admitted to five DUI offender programs in a
      Northern California county. Interviews averaged 1 hour in length and were
      conducted in the programs by trained interviewers. The response rate was 71% for
      whites and 84% for Mexican Americans. RESULTS: At the time of the arrest, Mexican
      Americans were driving cars older than those driven by whites. A higher
      proportion of Mexican Americans than whites reported having consumed 10 or more
      drinks before the arrest. The most frequent locale for drinking before the arrest
      was "home or friends' home" for Mexican Americans and a "bar/tavern/club" for
      whites. CONCLUSIONS: Cross-ethnic differences related to the circumstance of the
      arrest (car year) do not fully explain the higher rates of DUI arrest among
      Mexican Americans, compared with whites. Differences in drinking locale before
      arrest suggest that server intervention efforts may not be as effective in
      preventing DUI for Mexican Americans as they are for whites. Prevention
      interventions with Mexican Americans should center on the family, as a means to
      minimize drinking at home and decrease the large number of drinks consumed on a
      particular occasion by Mexican Americans.

PMID- 11838913
TI  - Adolescent alcohol expectancies in offspring from families at high risk for
      developing alcoholism.
AB  - OBJECTIVE: The present study investigated alcohol expectancies derived from the
      Alcohol Expectancy Questionnaire (AEQ) in parents and their adolescent offspring.
      It was of interest to determine whether alcohol expectancies would differ by risk
      status, and whether those differences were influenced by parental beliefs.
      METHOD: Children/ adolescents aged 8 to 18, from families at high risk for
      developing alcoholism (n = 69; 37 males) and from low-risk control families (n =
      46; 25 males), were evaluated annually. At every assessment, each child and one
      parent were administered the AEQ and interviewed to determine drinking status.
      Data for two time points approximately 3 years apart were analyzed. RESULTS: In
      early adolescence, high-risk offspring expected more improvement in social
      functioning when under the influence of alcohol than did low-risk controls.
      However, by age 16, risk group differences were not seen. Higher scores on two of
      the AEQ scales (Social Behavior and Relaxation) predicted the age of onset for
      regular drinking, whereas one scale (Social Behavior) predicted drinking
      behavior. In addition, high-risk offspring were found to have beliefs about the
      effects of alcohol that were similar to those of their parents, in contrast to
      low-risk offspring and their parents, who displayed significant negative
      correlations. CONCLUSIONS: This report confirms previous studies relating alcohol
      expectancies to drinking behavior (frequency, quantity per occasion, social
      consequences). Alcohol expectancies also were found to predict the age of onset
      to begin regular drinking in the combined group of adolescents studied, although
      risk differences in age of onset were not influenced by differing expectations
      concerning the effects of alcohol. These results suggest that the risk
      differences in expectancies that were seen in young adolescents (approximately
      age 13) may be due to the transmission of parental beliefs to their offspring.
      The absence of risk differences by late adolescence (approximately age 16)
      suggests that other factors (e.g., peer influences or experience drinking
      alcohol) also play a role.

PMID- 11838912
TI  - Childhood and adolescent predictors of alcohol abuse and dependence in young
      adulthood.
AB  - OBJECTIVE: To provide a comprehensive examination of childhood and adolescent
      predictors of alcohol abuse and dependence at age 21, theoretically guided by the
      social development model. METHOD: Data were taken from an ethnically diverse
      urban sample of 808 students (51% male), surveyed at age 10 and followed
      prospectively to age 21 in 1996. Potential predictors of alcohol abuse and
      dependence at age 21 were measured at ages 10, 14 and 16. Relationships between
      these predictors and alcohol abuse and dependence were examined at each age, to
      assess changes in their patterns of prediction over time. RESULTS: Strong bonding
      to school, close parental monitoring of children and clearly defined family rules
      for behavior, appropriate parental rewards for good behaviors, high level of
      refusal skills and strong belief in the moral order predicted a lower risk for
      alcohol abuse and dependence at age 21. Of these, strong bonding to school
      consistently predicted lower alcohol abuse and dependence from all three ages
      (10, 14 and 16). By contrast, youths who had a higher risk of alcohol abuse and
      dependence at age 21 engaged in more problem behaviors, had more opportunities to
      be involved with antisocial individuals and spent more time with and were more
      bonded to those individuals, viewed fewer negative consequences from antisocial
      behaviors and held more favorable views on alcohol use. Of these, prior problem
      behaviors and antisocial opportunities and involvements at ages 10, 14 and 16
      consistently predicted alcohol abuse and dependence at age 21. CONCLUSIONS: These
      important malleable predictors, identifiable as early as age 10, provide
      potential intervention targets for the prevention of alcohol abuse and dependence
      in early adulthood.

PMID- 11838914
TI  - Prospective risk factors for alcohol misuse in late adolescence.
AB  - OBJECTIVE: This longitudinal study investigated Grade-7 and Grade-10 risk factors
      for alcohol misuse at Grade 12. Alcohol misuse was conceptualized as problem
      related drinking (e.g., missing school), high-risk drinking (e.g., drunk driving)
      and high consumption. METHOD: Prospective analyses using two-part models
      predicted any alcohol misuse and the amount of misuse (given that some has
      occurred) for over 4,200 (52% male) participants in the RAND Adolescent Panel
      Study. Predictor variables were demographics, substance use and exposure, prodrug
      attitudes, rebelliousness and deviant behavior, self-esteem, family structure and
      relations, and grades. RESULTS: Grade-7 predictors of alcohol misuse 5 years
      later included early drinking onset, parental drinking, future intentions to
      drink, cigarette offers, difficulty resisting pressures to smoke, being white,
      being male, having an older sibling, deviant behavior and poor grades. By Grade
      10, predictors of alcohol misuse 2 years later included drinking and marijuana
      use by self and peers, future intentions to drink, difficulty resisting pressures
      to drink and use marijuana, being male, coming from a disrupted family and
      deviant behavior. Somewhat different predictors were identified for problem
      related, high-risk and high consumption drinking, emphasizing the importance of
      investigating multiple dimensions of misuse. CONCLUSIONS: The high social
      acceptability of alcohol use makes prevention difficult. Curbing alcohol misuse
      may be a more attainable goal than preventing any use. These results indicate
      that predictors of misuse in late adolescence can be identified by Grade 7 and
      are generally visible and modifiable. Prevention efforts should begin by early
      adolescence, address both familial and peer influences to drink and use other
      substances, and take into account problems that predict alcohol misuse (e.g.,
      poor academic performance and early deviant behavior).

PMID- 11838915
TI  - The effects of alcohol consumption on mortality and morbidity: a 26-year follow
      up study.
AB  - OBJECTIVE: To investigate the long-term effects of the consumption of alcohol on
      mortality and morbidity. METHOD: A sample of 32,185 (50.5% female) individuals
      was randomly selected from the 450,000 inhabitants of Stockholm County, Sweden,
      in 1969. Alcohol consumption data were obtained from postal questionnaires;
      response rate was 87% (n = 28,001). Data on mortality and morbidity were obtained
      from the National Cause of Death Register, the Cancer Register and the Inpatient
      Register 1971-1996. RESULTS: The reference groups were moderate consumers of
      alcoholic beverages. High-consumption men had increased risks of mortality from
      cardiovascular diseases (relative risk ratio [RR] = 1.28; 95% confidence interval
      [CI]: 1.12-1.46), accidents or poisoning (RR = 2.10; CI: 1.67-2.65) and
      gastrointestinal diseases (RR = 4.65; CI: 2.93-7.36). High-consumption women had
      an increased risk of mortality only from accidents or poisoning (RR = 2.95; CI:
      1.82-4.78) and gastrointestinal diseases (RR = 3.60; CI: 1.40-9.24). For low
      consumption women, there was an increased risk of mortality from cardiovascular
      diseases (RR = 1.25; CI: 1.07-1.47). Low-consumption men also had an increased
      mortality from cardiovascular diseases (RR = 1.23; CI: 1.05-1.44). The results
      with respect to morbidity almost mirrored the results for mortality, with one
      exception; for low-consumption men, the morbidity from cardiovascular diseases
      was not increased. CONCLUSIONS: The mortality and morbidity associated with
      different levels of alcohol consumption are associated with the same diseases,
      which suggests that alcohol may be one of the causative factors for these
      diseases. The reasons for the differences between genders, regarding responses to
      the negative effects of alcohol consumption, are still unknown.

PMID- 11838916
TI  - Alcohol and mortality from external causes.
AB  - OBJECTIVE: The aim of this study was to examine the relationship between alcohol
      consumption, considering both volume of intake and drinking pattern, and the risk
      of death from external causes. METHOD: A prospective study of mortality from
      external causes was conducted using data from the 1988 National Health Interview
      Survey linked with the National Death Index for 1988 through 1995. During the 7.5
      year follow-up interval, there were 155 deaths from external causes among the
      42,910 adults 18 years of age and over included in the sample. Proportional
      hazards models were used to adjust for censoring due to competing causes of death
      and for the effects of potentially confounding background variables including
      age, gender, marital status, education, smoking and poor health at baseline.
      RESULTS: Relative to lifetime abstainers and infrequent drinkers, the risk of
      death from external causes increased directly with volume of intake, exhibiting a
      logarithmic-shaped risk curve. There was no evidence of reduced risk among light
      or moderate drinkers. When usual quantity and frequency were examined, the only
      drinkers at significantly increased risk were those who drank less than once a
      month but usually drank 5+ drinks (or, to a lesser extent, 3+ drinks) and those
      who drank at least twice a week and usually drank 2+ drinks. Former drinkers also
      were at increased risk. Age strongly affected the drinking pattern parameters.
      CONCLUSIONS: Quantity and frequency of drinking are proxies for in-the-event
      risks associated with alcohol intake and their cumulative effect on mortality
      risk. The results are discussed with particular attention to the role of factors
      that may affect the association between usual quantity of drinks consumed and the
      in-the-event risk of mortality from external causes.

PMID- 11838917
TI  - A signal detection approach to the combined effects of work stressors on alcohol
      consumption.
AB  - OBJECTIVE: To test the relationship between work stress and alcohol consumption
      and the efficacy of signal detection analysis in a work stress-alcohol
      consumption study. METHOD: The study was part of a Work Site Health Project,
      which included a stress reduction program, at a manufacturing company in Osaka,
      Japan. The study design was a cross-sectional survey. The participants were
      Japanese male whitecollar workers (N = 457; 30 to 50 years old) in the head
      administrative office of a large manufacturing company. Measurements consisted of
      demographic variables of the workers (age, marital status, manner of living and
      Type A personality), work stress measures, working hours and alcohol consumption.
      RESULTS: Of eight independent variables, six significant predictors of heavy
      alcohol consumption were identified in the first signal detection analysis. Of
      these six variables, job demand and skill discretion were work-stress-related
      measures. In the second multiple regression analysis, skill discretion and job
      demand were significant predictors of alcohol consumption among the workers in
      two of the seven subgroups categorized by the first signal detection analysis.
      CONCLUSIONS: It was revealed that work stress did relate to alcohol consumption.
      However, the effect of the work stress upon alcohol consumption was limited to
      specific types of workers with multiple specific attributes. It was also inferred
      that the signal detection approach is an effective approach to the work stress
      alcohol consumption relationship.

PMID- 11838918
TI  - Evaluating the effects of a brief motivational intervention for injured drinkers
      in the emergency department.
AB  - OBJECTIVE: The study aim was to test whether a brief motivational intervention,
      with or without a booster session, would improve drinking-related outcomes more
      than standard Emergency Department (ED) treatment. METHOD: The study population
      consisted of 539 (78% male) injured patients treated in the ED and discharged to
      the community following their treatment. Injured patients met inclusion criteria
      if they were assessed as hazardous or harmful drinkers by scoring eight or more
      on the AUDIT and/or having alcohol in their system at the time of their injury or
      ED visit. Patients were randomly assigned to either standard care (SC), brief
      intervention (BI) or brief intervention plus a booster session (BIB). At 1-year
      follow-up, 447 patients (83% of the sample) were re-interviewed to measure
      alcohol-related negative consequences, injuries and drinking. RESULTS: Patients
      receiving BIB, but not B1 patients, reduced alcohol-related negative consequences
      and alcohol-related injuries more than did those in the SC group. All three
      groups reduced their days of heavy drinking. Patients with histories of hazardous
      drinking responded to BIB, whether or not they had consumed alcohol prior to
      their injury. CONCLUSIONS: Together, these results indicate that the effects of a
      booster session that is added to a brief intervention in the ED can be helpful to
      injured patients with a history of hazardous or harmful drinking, irrespective of
      whether they have consumed alcohol prior to their injury.

PMID- 11838919
TI  - A longitudinal model of intake symptomatology, AA participation and outcome:
      retrospective study of the project MATCH outpatient and aftercare samples.
AB  - OBJECTIVE: The present study used data gathered in Project MATCH to
      longitudinally assess intake symptomatology, Alcoholics Anonymous (AA)
      participation, and outcome. Three primary constructs were considered: intake
      symptomatology, engagement in prescribed AA-related activities and functioning
      after engagement in AA-related behaviors. METHOD: The participants were 480
      outpatient and 434 aftercare clients who participated in Project MATCH. RESULTS:
      Similar findings were found for each sample. Intake symptomatology positively
      predicted AA participation during the first 6 months following treatment.
      Although network support for drinking was negatively related to AA participation,
      such support did not mediate the relationship between intake symptomatology and
      subsequent AA participation. AA participation, in turn. positively predicted
      frequency of abstinent days in Months 7-12 posttreatment. This latter
      relationship was mediated by perceived self-efficacy to avoid drinking (Month 6).
      AA participation was positively related to self-efficacy to avoid drinking,
      which, in turn, predicted more days abstinent. One difference between the
      outpatient and aftercare samples emerged, involving the latent construct intake
      symptomatology. Intake symptomatology among outpatients was not predictive of
      percentage of abstinent days (Months 7-12), whereas intake symptomatology was
      negatively predictive of percentage of abstinent days in the aftercare sample.
      CONCLUSIONS: Intake symptomatology positively predicted participation in AA,
      which predicted subsequent abstinent days. The positive relationship between AA
      participation and self-efficacy to avoid drinking may explain in part why AA
      engagement predicts subsequent increases in abstinence.

PMID- 11838920
TI  - The relationship between alcohol screening questionnaires and mortality among
      male veteran outpatients.
AB  - OBJECTIVE: This study evaluated whether responses to alcohol screening
      questionnaires predicted mortality in a Department of Veterans Affairs (VA)
      primary care population. METHOD: This study involved 5,703 male outpatients (mean
      age = 64) who were enrolled in General Internal Medicine clinics at three
      Veterans Affairs (VA) medical centers and returned mailed questionnaires in 1993
      94. The two questionnaires included the CAGE and Alcohol Use Disorders
      Identification Test (AUDIT) alcohol screening tests. Mortality was ascertained
      using the VA Beneficiary Identification and Record Locator System. Five-year
      crude and adjusted mortality rates were calculated for patients who screened
      positive and patients who screened negative on each alcohol screening test.
      RESULTS: The risk of mortality was increased among drinkers who scored > or = 8
      on the full AUDIT (hazard ratio: 1.47; 95% confidence interval [CI]: 1.08-2.00)
      or the three AUDIT consumption questions (1.58; 1.11-2.27), after adjusting for
      age, smoking, sociodemographic characteristics and chronic illnesses. The risk of
      mortality was also increased among drinkers who reported drinking > or = 3 drinks
      daily (1.69; 1.28-2.22) or prior alcohol treatment (1.66; 1.27-2.17), in "fully
      adjusted" models. A positive CAGE score (> or = 2) was associated with
      significantly increased risk of mortality among drinkers in a model adjusted only
      for age and smoking (1.27; 1.02-1.58). Among nondrinkers, neither a positive CAGE
      score (> or = 2) nor report of prior alcohol treatment was associated with
      increased risk of mortality. CONCLUSIONS: VA outpatients who reported drinking
      during the previous year and who had a positive result on an alcohol screening
      test experienced higher mortality over the subsequent 5 years than did patients
      who screened negative.

PMID- 11838921
TI  - Invariance of the MAST across religious groups.
AB  - OBJECTIVE: The Michigan Alcoholism Screening Test (MAST), a commonly used
      instrument of alcohol-related problems, was examined to determine whether it
      assessed the same constructs in individuals from religions with different
      proscriptions regarding the use of alcohol. METHOD: The MAST was completed by
      participants in the longitudinal Joint Child Health Project when they were
      approximately 23 years old. Subjects of this study (N= 747; 505 men) were 465
      Hindus, 223 Catholics and 59 Muslims who reported drinking alcohol. Measurement
      invariance, the determination that the same constructs are being measured across
      groups, was tested by comparing factor invariance using multigroup structural
      equation modeling. RESULTS: The Hindu and Catholic groups had similar factor
      structures to those found in previous Australian, Canadian and U.S. samples.
      Metric invariance was obtained for the Hindu and Catholic groups, but not for the
      Muslim group. CONCLUSIONS: These findings suggest the measurement of MAST factors
      is invariant across a fairly broad segment of the population in which the MAST
      might be used. However, the lack of invariance in this sample of Muslims suggests
      that the MAST is not an appropriate instrument to use among all groups of
      drinkers. These findings highlight the importance of testing for invariance when
      using psychological measures to compare heterogeneous samples.

PMID- 11838922
TI  - Confirmatory factor analyses of the alcohol use disorders identification test
      (AUDIT) among adolescents treated in emergency departments.
AB  - OBJECTIVE: The Alcohol Use Disorders Identification Test (AUDIT) is a 10-item
      instrument designed by the World Health Organization to assess problematic
      drinking. The objective of this study was to conduct confirmatory factor analysis
      of the AUDIT in a sample of adolescents and young adults who were treated in
      emergency departments. METHOD: Adolescents and young adults (N= 103, 55 males),
      ranging in age from 12 to 20.9 years (mean [SD] age = 17.5 [2.1]), completed the
      AUDIT. Confirmatory factor analyses were conducted using LISREL 8.20 software to
      test the one-factor, two-factor and three-factor solutions for the AUDIT reported
      in the literature. RESULTS: Goodness-of-fit indices indicated that a correlated
      two-factor solution, consisting of a consumption factor and an alcohol-related
      problems factor, provides the best fit to the data. The three-factor solution
      fits the data equally well, but Factor 2 (dependency) and Factor 3 (problems)
      correlate 1.00. The one-factor solution did not provide a good fit to the data.
      CONCLUSIONS: Our findings support those of others who have reported that the
      AUDIT assesses a consumption factor and an alcohol-related problems factor among
      primary care patients at risk for problematic drinking behavior.

PMID- 11838923
TI  - Coronary artery disease in Indians.

PMID- 11838924
TI  - Stents in the management of congenital heart disease in pediatric and adult
      patients.

PMID- 11838925
TI  - Increased risk of acute myocardial infarction associated with beedi and cigarette
      smoking in Indians: final report on tobacco risks from a case-control study.
AB  - BACKGROUND: Tobacco smoking is an important risk factor for ischemic heart
      disease. In India, tobacco is smoked both as cigarettes and beedies. No studies
      have evaluated their importance as risk factors for ischemic heart disease among
      the Indian population. The present study explores the importance of smoking
      either cigarettes or beedies as risk factors for acute myocardial infarction.
      METHODS AND RESULTS: The study had a case-control design and was conducted in a
      tertiary teaching hospital in Bangalore. Three hundred subjects aged 30-60 years
      with a first acute myocardial infarction and 300 age- and sex-matched controls
      were recruited prospectively. Smoking, dietary and social history were recorded,
      body mass index and waist-hip ratio measured, and blood glucose, lipids, fasting
      plasma and insulin levels estimated. Cases and controls had a mean age of 47.2
      years and 46.8 years, respectively. There were 279 (93%) males in each group.
      Diabetes mellitus (odds ratio 2.69, p<0.0009). hypertension (odds ratio 2.36,
      p=0.0009), fasting and post-load blood glucose (p<0.0001). and waist-hip ratio
      (p<0.0001) were found to be important risk factors for acute myocardial
      infarction. Smoking was an independent risk factor with a clear dose effect.
      Adjusted odds ratio for smoking > or = 10 cigarettes/day was 3.58 (p<0.0001) and
      was 4.36 (p<0.0001) for smoking > or = 10 beedies/day. CONCLUSIONS: Smoking > or
      = 10 cigarettes or beedies/day carries an independent four-fold increased risk of
      acute myocardial infarction. This reiterates the need for urgent tobacco control
      measures in India.

PMID- 11838926
TI  - Surgical repair of left ventricular aneurysms: a comparative evaluation of linear
      versus Dor's repair.
AB  - BACKGROUND: Resection and linear repair of aneurysms of the left ventricle alter
      its geometry and thereby reduce its performance over the long term. Hence, Dor's
      circular patch repair was advocated to maintain the geometry of the left
      ventricle. However, the superiority of this procedure over linear repair is
      debatable. METHODS AND RESULTS: We retrospectively analyzed 95 cases of left
      ventricular aneurysm repair--28 cases by Dor's procedure and 67 by linear repair.
      The age group, symptoms, risk-factor profile and severity of coronary artery
      disease were comparable in both the groups, but the cardiopulmonary bypass and
      mean aortic cross-clamp time were longer in those treated with Dor's procedure.
      The left internal mammary artery could be grafted to the left anterior descending
      artery or diagonal branch in 13 cases in the group undergoing Dor's procedure
      (group I) versus 14 cases in the group undergoing linear repair (group II). There
      was no mortality in group I while there were 7 deaths in group II. Patients in
      group I were followed up for up to 2 years and those in group II for up to 13
      years. During follow-up, 16/2 8 remained in NYHA functional class I or II in
      group I versus 24/67 in group II. The mean preoperative left ventricular ejection
      fraction was 34.9% in group I which improved to 39.7% during follow-up. In group
      II, the mean preoperative left ventricular ejection fraction was 37.2% which
      improved to 41.5% during follow-up. This difference was not statistically
      significant. CONCLUSIONS: In our retrospective study, we did not observe any
      superiority of Dor's repair over linear repair for left ventricular aneurysm as
      regards NYHA functional class and left ventricular ejection fraction. However,
      follow-up with Dor's repair was short (up to 2 years). Hence, no definite
      conclusions can be drawn.

PMID- 11838927
TI  - Short-term (48 hours) versus long-term (7 days) antibiotic prophylaxis for
      permanent pacemaker implantation.
AB  - BACKGROUND: Infection following permanent pacemaker implantation is a dreaded
      complication. Antibiotic prophylaxis for 1-10 days at the time of implant has
      been used in the past but there is no consensus regarding its duration. We
      carried out a prospective, randomized study of two durations of antibiotic
      prophylaxis to determine which one was more effective. METHODS AND RESULTS: One
      hundred and seventy-eight patients undergoing permanent pacemaker implantation
      for the first time were randomized to receive short duration (group A, n = 8 8)
      or longer duration (group B, n = 90) antibiotic prophylaxis for 2 days and 7
      days, respectively. Patients in both groups received cloxacillin 2 g 2 hours
      prior to the procedure followed by ampicillin and cloxacillin (50 mg/kg/day in 4
      divided doses) and gentamicin (3 mg/kg/day in 2 divided doses) for the respective
      duration. Patients were followed up for 1-17.3 months (9.3 +/- 1.8 months) in
      group A and 1-16.5 months (8.9 +/- 2 months) in group B. One patient in group B
      had an infection at the pacemaker site and two patients in each group had to
      undergo reimplantation due to pus in the pocket. There was no significant
      difference in the primary end-point in both groups. CONCLUSIONS: A short course
      (48 hours) of antibiotic prophylaxis following permanent pacemaker implantation
      is as effective as a longer course (7 days).

PMID- 11838928
TI  - Emergency transcatheter balloon recanalization of acutely thrombosed modified
      Blalock-Taussig shunts.
AB  - BACKGROUND: Modified Blalock-Taussig shunts are used to palliate a variety of
      cyanotic heart diseases associated with reduced pulmonary blood flow. Acute shunt
      thrombosis in patients with shunt-dependent pulmonary blood flow can result in
      life-threatening hypoxia. We describe our experience of emergency transcatheter
      recanalization in 5 severely hypoxic children with acute shunt occlusion. METHODS
      AND RESULTS: Five patients with ages ranging between 5 and 24 months (median 11
      months) and weight ranging from 4 to 8 kg (median 5 kg) presented with severe
      hypoxia, acidosis and hypotension following acute occlusion of modified Blalock
      Taussig shunts placed 11 days to 12 months ago. As severe hypoxia (saturation
      range 3 5%-5 0%), acidosis and a state of shock in all the patients increased the
      risk for a redo surgical procedure, they were taken up for emergency
      transcatheter recanalization within 2-6 hours of hospitalization. This was done
      by positioning a Judkin's right coronary catheter at the mouth of the thrombosed
      shunt, crossing the shunt with a guidewire and serial dilatations with coronary
      and/or peripheral angioplasty balloons to the size of the graft. This technique
      was immediately successful in 4 of the 5 patients, thereby avoiding a repeat
      palliative operation. In 2 patients with residual stenosis, stents were used to
      restore luminal patency. One patient with acute stent thrombosis was managed
      successfully with local delivery of thrombolysis for 36 hours, which resulted in
      good luminal patency. At follow-up after 6 and 12 months, the shunts in both the
      stented patients are patent, with an oxygen saturation of 78% and 80%,
      respectively. In 2 other patients who had undergone plain balloon angioplasty,
      the shunts remained patent for 11 days (died of bronchopneumonia and septicemia)
      and 3 months, respectively. The procedure was unsuccessful in one very sick
      patient in whom the shunt had a tortuous course. CONCLUSIONS: Transcatheter
      recanalization of an acutely thrombosed Blalock-Taussig shunt is feasible. It can
      offer satisfactory short-term palliation in selected patients. Stents may play a
      role in patients with residual narrowing after dilatation. The procedure can be
      expeditiously accomplished in an emergency situation in a severely hypoxic child
      and may be a realistic alternative to surgery or thrombolysis.

PMID- 11838929
TI  - A case-control study of plasma homocysteine levels in South Indians with and
      without coronary artery disease.
AB  - BACKGROUND: An increased level of plasma homocysteine is being recognized as a
      new risk factor for coronary artery disease. Since there are not enough data
      about its importance in Indians with coronary artery disease, we aimed to assess
      the significance of plasma homocysteine as a coronary risk factor in South Indian
      patients. METHODS AND RESULTS: In a case-control study, fasting plasma
      homocysteine levels were estimated in 565 subjects, of whom 221 were cases and
      344 were controls. Of the 221 clinically defined cases, 112 underwent coronary
      angiography while 107 of the 344 controls had angiographically proven normal
      coronary arteries. Ninety healthy volunteers from the community were also
      included as controls. Fluorescent polarization immunosorbent assay was used to
      measure plasma homocysteine levels. In 12 patients, this method was compared to
      high pressure liquid chromatography and was found to give comparable results. The
      mean plasma homocysteine level was 18.30 +/- 10.08 micromol/L in clinically
      defined cases and 18.04 +/- 10.69 micromol/L in controls. Similarly, in
      angiographicallyproven coronary arterydisease patients, the mean plasma
      homocysteine levelwas 18.49 +/- 10.04 micromol/L and in individuals with
      angiographically normal coronary arteries, it was 19.16 +/- 11.38 micromol/L.
      CONCLUSIONS: There is no statistically significant difference in plasma
      homocysteine levels between controls and cases with coronary artery disease. The
      mean plasma homocysteine levels in controls as assessed by fluorescent
      polarization immunosorbent assay in the present study population are higher as
      compared to other published reports.

PMID- 11838930
TI  - Total anomalous pulmonary venous connection: surgical experience in Indians.
AB  - BACKGROUND: We report a retrospective analysis of the demographic. morphological
      and clinical profiles of patients along with results of operative repair for
      total anomalous pulmonary venous connection. METHODS AND RESULTS: In the last 15
      years, 248 patients (168 boys, 80 girls) underwent repair for total anomalous
      pulmonary venous connection. Their ages ranged from I day to 24 years (median 8
      months) and 145 of them were < or = 1 year of age. The patients' weight ranged
      from 2 to 52 kg (median 5 kg). About 70% of patients (n = 174) were less than the
      50th percentile of predicted weight for age and sex. The anomalous connection was
      supracardiac in 134 (54%), cardiac in 80 (32.2%), infracardiac in 9 (3.6%) and
      mixed in 25 (10.1%) patients. Fifty (20.2%) patients had obstructed drainage and
      76 patients (30.2%) had moderate or severe pulmonary arterial hypertension. Forty
      five patients (18.1%) had to be operated upon on an emergency basis. All the
      patients were operated upon using moderately hypothermic cardiopulmonary bypass.
      In 114 patients, circulatory arrest was used. There were 45 (19.1%) in-hospital
      deaths. The major causes of early death were pulmonary arterial hypertensive
      crisis in 19 (7.7%) and low cardiac output syndrome in 17 (6.9%) patients. Age <
      or = 1 year (odds ratio 2.16; 95% confidence interval: 1.22-3.82, p=0.008),
      severe pulmonary arterial hypertension (odds ratio 5.86; 95% confidence interval:
      2-17, p=0.001), and need for emergency surgery (odds ratio 3.65; 95% confidence
      interval: 1.59-8.38, p=0.002) were independent risk factors for early death.
      Follow-up ranged from 1 to 180 months (median 48 months). There were 4 lake
      deaths. Actuarial survival at 12 years was 92.6% +/- 2.8%. CONCLUSIONS: In Indian
      circumstances, mortality continues to be high in infants with total anomalous
      pulmonary venous connection. Severe pulmonary arterial hypertension appears to be
      the most important predictor of operative mortality. Severe malnutrition, delayed
      diagnosis and late referrals possibly contribute to the high mortality.

PMID- 11838931
TI  - Carotid artery involvement in patients of atherosclerotic coronary artery disease
      undergoing coronary artery bypass grafting.
AB  - BACKGROUND: Patients with concomitant critical carotid and coronary artery
      disease are at risk of major neurological events while undergoing coronary artery
      bypass grafting. The presence of carotid artery stenosis increases the stroke
      rate in the perioperative period. In an effort to reduce the stroke rate, many
      institutions perform routine preoperative noninvasive assessment of the carotid
      arteries. METHODS AND RESULTS: We analyzed the clinical and laboratory data of
      1,200 patients who underwent coronary artery bypass surgery in the last 2 years.
      Carotid Doppler was normal in 186 patients (15.5%), and showed <30% stenosis in
      796 (66.3%), 30%-50% in 110 (9.2%), 50%-70% stenosis in 64 (5.3%) and critical
      (>70%) stenosis in 44 (3.7%) patients. Conventional risk factors such as
      hypercholesterolemia, hypertension, smoking and family history were not
      independent predictors of carotid artery stenosis. However, diabetes as a risk
      factor had a significant association with carotid artery disease (79.6% v. 43.8%,
      p<0.02). There was a trend towards increased prevalence of carotid artery
      stenosis in patients with > or = 2 risk factors (84.3% v. 68.8%). Patients with
      significant carotid artery stenosis had severe coronary artery disease (triple
      vessel disease 93.3%, left main coronary artery disease 12.0%). Out of 44
      patients with critical carotid artery stenosis, 27 were subjected to carotid
      angiography. Doppler findings correlated well with angiography. Seventeen
      patients underwent carotid artery intervention. None had any perioperative
      neurological events. A total of 5 (0.4%) patients had a major stroke. Coronary
      artery bypass grafting was done in 27 patients with critical stenosis without any
      intervention. The stroke rate (11.1%) was higher in these patients compared to
      patients with < 70% carotid artery disease or post-carotid intervention (2.5%)
      patients. Thus, untreated >70% carotid artery stenosis was associated with a
      higher stroke rate. CONCLUSIONS: Doppler screening of the carotid artery is
      helpful in detecting the subgroup of patients at increased risk of stroke.
      Patients with critical carotid artery stenosis should be subjected to
      angiography. Prophylactic intervention may reduce the occurrence of stroke in the
      perioperative period.

PMID- 11838932
TI  - Noncompaction of left ventricular myocardium in the presence of calcific aortic
      stenosis in an adult.
AB  - We describe an adult patient with a hitherto unreported association of severe
      aortic stenosis with extensive noncompaction of the left ventricular myocardium
      without any hypertrophy; however, there was severe left ventricular systolic
      dysfunction in the presence of a normal-sized left ventricular cavity on two
      dimensional echocardiography. This condition was differentiated from persistence
      of embryonic intramyocardial sinusoids by selective coronary angiography.

PMID- 11838933
TI  - Ruptured idiopathic pulmonary artery aneurysm: unusual case of hemothorax treated
      by selective embolization.
AB  - Aneurysm of the peripheral pulmonary arteries is rare. Rupture of pulmonary
      artery aneurysms manifesting as recurrent hemoptysis with exsanguination is well
      recognized. We report the case of a young woman who presented with massive
      hemothorax and shock at the sixth month of pregnancy due to a ruptured lingular
      artery aneurysm. She was treated with selective coil embolization of the lingular
      artery to achieve hemostasis. Subsequently, clot evacuation from the pleural
      space was done. This case is reported for its unsuspected presentation, rarity
      and to highlight the use of catheter coil embolization to achieve control of
      bleeding and exclusion of the aneurysm from the pulmonary circulation.

PMID- 11838934
TI  - Concurrent percutaneous atrial septal defect closure and pulmonary valvuloplasty.
AB  - Severe pulmonary valve stenosis in association with a large atrial septal defect
      is uncommon. Simultaneous percutaneous closure of the atrial septal defect and
      pulmonary valvuloplasty appears to be an attractive modality when compared to
      patients with these two lesions being subjected to surgery or being treated
      percutaneously at different sittings. We encountered two cases, both with
      significant pulmonary valvular stenosis associated with atrial septal defect
      (fossa ovalis type). Both lesions were successfully treated percutaneously in the
      same sitting. Pulmonary valvuloplasty was done initially and the atrial septal
      defect closed later to minimize catheter manipulation after device implantation.

PMID- 11838935
TI  - Large thrombus in the pulmonary arteries in a case of atrial septal defect
      Eisenmenger syndrome.
AB  - A 41-year-old man with atrial septal defect-Eisenmenger syndrome presented with
      progressively worsening breathlessness. The echocardiogram, computerized
      tomographic scan and magnetic resonance imaging of the thorax showed dilated
      pulmonary arteries and large thrombi in the right and left pulmonary arteries.
      Contrast-enhanced computerized tomographic scan was better than magnetic
      resonance imaging in picking up the thrombus. The possibility of in situ thrombus
      formation was considered more likely than thromboembolism, as there were none of
      the acute symptoms expected with the embolization of such large thrombi.

PMID- 11838936
TI  - Reversible myocarditis in a patient receiving clozapine.
AB  - Myocarditis is a rare and potentially life-threatening complication of clozapine.
      We report the case of a 2 6-year-old patient who developed reversible myocarditis
      during treatment with clozapine for chronic resistant schizophrenia. The patient
      recovered rapidly on withdrawal of clozapine and with supportive management.

PMID- 11838937
TI  - Transcatheter coil occlusion of hepatic arteriovenous malformation in a neonate.
AB  - A 3-day-old neonate was diagnosed to have severe congestive heart failure due to
      a large shunt through a hepatic arteriovenous malformation. Percutaneous
      transcatheter delivery of two detachable coils resulted in complete abolition of
      the shunt. The patient showed dramatic clinical improvement and resolution of the
      heart failure, which was sustained on follow-up. This case represents a novel use
      of detachable occluding spring coils designed primarily for occluding patent
      ductus arteriosus.

PMID- 11838939
TI  - Clopidogrel.

PMID- 11838938
TI  - Treatment of recurrent attacks of supraventricular tachycardia during pregnancy
      causing complications in both mother and fetus.
AB  - Cardiac arrhythmias including supraventricular tachycardia are commonly
      encountered during pregnancy. The case of a young Indian woman with recurrent
      attacks of supraventricular tachycardia during pregnancy which was managed with
      adenosine and verapamil is reported. The possible mechanisms of maternal and
      fetal complications are discussed.

PMID- 11838940
TI  - Chronic dissection of the descending thoracic aorta treated by endovascular stent
      graft placement.

PMID- 11838941
TI  - Procedural outcomes and long-term survival among patients undergoing percutaneous
      coronary intervention of a chronic total occlusion in native coronary arteries: a
      20-year experience.

PMID- 11838942
TI  - The molecular evolution and DNA profiling of toxic cyanobacteria.
AB  - Rapid and sensitive methods for the detection and genetic characterization of
      cyanobacteria have been developed based on DNA amplification techniques. This
      article describes the molecular methods that have been used to characterize
      cyanobacteria and their use as tools to identify toxin-producing strains.
      Different species and strains were compared using restriction fragment length
      polymorphism (RFLP) of amplified fragments of the phycocyanin gene and the 16S
      23S rRNA internal transcribed spacer.

PMID- 11838944
TI  - Advances towards integrated biodetection systems for environmental molecular
      microbiology.
AB  - To overcome many of the limitations associated with indirect detection methods,
      new techniques for the sensitive, specific, and direct detection of nucleic acids
      are required in order to accurately and quantitatively ascribe phenotype/function
      to uncultivated microorganisms. However, if advanced diagnostic and detection
      systems are going to be applied in environmental microbiology, future
      "biodetection" technologies and systems must be developed not from the point of
      view of the detector, but from the unique aspects of the environmental sample and
      the entire analytical process. This article highlights recent advances in nucleic
      acid-based technologies, and looks towards future advances that may address the
      broad needs and conditions imposed by environmental molecular microbiology.

PMID- 11838943
TI  - Analysis of specific bacteria from environmental samples using a quantitative
      polymerase chain reaction.
AB  - This article describes the use of quantitative PCR for measuring bacterial
      abundance in environmental samples. The two approaches discussed are: 1) The use
      of an internal PCR standard constructed to be the same size and have the same
      sequence as the primary amplification target, but differing from the primary
      target by 2-3 bases, corresponding to a unique restriction site. This allows the
      amount of target amplicon to be compared with the internal standard and
      circumvents the problem of differential amplification efficiencies when using
      dissimilar targets and standard amplicons. 2) The use of Taqman technology
      (Applied Biosystems, Foster City, California) with a dual labeled oligonucleotide
      probe which binds internal to the PCR primers. The detection of Bacteroides is
      used as an example for both approaches.

PMID- 11838945
TI  - Raising the social yield of research: challenge facing biotechnology.
AB  - The biological revolution is the latest in a series of scientific revolutions
      that have ushered in a new era in physics, chemistry, industry, and composite
      materials. The latest instruments of life - bioengineering for and by the living 
      challenge mankind with a number of fundamental questions, while offering an
      unprecedented series of opportunities. Alternative biotechnologies, biological
      agriculture for the environment, genomics applied to preventive medicine, genetic
      engineering are just a few of the benefits mankind may reap from bioengineering.
      Modern society demands more knowledge, and it is up to public authorities to
      invest in outreach programs to make public the latest scientific activities and
      findings. In the case of biotechnologies, it is particularly true that the
      product of research is not complete until its benefits are returned to society.

PMID- 11838946
TI  - From molecular biology to biotics: the development of bio-, info- and nano
      technologies.
AB  - Important scientific and technological developments have been achieved in biology
      during the last few years. Through the application of these developments,
      biotechnology will have a growing influence on the life sciences and their
      industrial use in the near future. This influence is evident in new drug design
      and in the development of diagnostic tests, bioelectronic equipment, and
      services. It has been observed that three fields of study are becoming
      increasingly interdependent: the molecular, the computational, and the
      mechanical. This convergence is achieved through the still closer relationships
      between biotechnologies, infotechnologies, nanotechnologies and microelectronics.

PMID- 11838947
TI  - Gene therapy: some results, many problems to solve.
AB  - Gene therapy is raising incredible hopes. The prospects of treating numbers of
      severe pathologies (hereditary, cancerous, degenerative or infectious) are vast.
      Nevertheless, the technological bolts to lift are still numerous, whether they be
      bringing the vectors into focus, the systems of expression of transgenes or the
      neutralization of immune responses of the host against the vector, the product of
      transgenes, or the knowledge of the considered pathologies of physiopathology.
      Solving these difficulties entails the gathering of multiple disciplines, from
      chemistry to medicine, passing through virology and immunology.

PMID- 11838949
TI  - Functional proteomics to exploit genome sequences.
AB  - The sequencing of various genomes has inaugurated a new stage in the
      understanding of normal and pathological cell function through the analysis of
      the role of proteins. Proteins, after all, that intervene in the different
      molecular mechanisms of life, during growth, reproduction, and in the interaction
      between cells, thus making it possible to describe the biology of integrated
      systems. In this article, we briefly describe the various stages in the
      progression of our knowledge, from the genome to the "functional" proteome.
      Emphasis is placed on a global approach to the protein-protein interactions used
      to describe the cellular "interactome".

PMID- 11838948
TI  - Gene therapy: progress and challenges.
AB  - Gene therapy is the delivery of new genetic material into a patient's somatic
      cells for the treatment of disease and is made possible through the development
      of viral and non-viral gene transfer vectors. In the first five years of gene
      therapy, clinical studies failed to yield efficacy data with the vectors
      available at that time. The lack of consistent clinical benefit prompted the
      United States National Institute of Health Recombinant DNA Advisory Committee to
      evaluate gene therapy research and conclude that substantial improvements in gene
      transfer vectors were needed in the areas of vector safety and control of the
      level and duration of gene expression, and to increase the understanding of the
      biological interaction of gene transfer vectors with the host. We will describe
      the progress in development of gene delivery technology, focusing on improvements
      in vector safety, analysis of vector biodistribution and GMP manufacturing of
      viral and non-viral gene transfer systems over the last six years since the
      report. Whereas 5 years ago, investigators tested every vector for every
      potential disease indication, the accumulated database now enables investigators
      to select a single vector based upon it's known performance in a wide number of
      animal models and human clinical studies. We will also highlight several
      directions investigators have taken to improve the safety and efficacy of gene
      therapy vectors.

PMID- 11838950
TI  - Applications of biotechnology to pharmacology and toxicology.
AB  - Strategies for the development of new more efficient drugs at a lower cost and
      for the evaluation of the effects of chemicals and metals on tissue and cell
      function are changing considerably. This is made possible by recent progress in
      various areas, particularly biotechnology and bioinformatics. The recent
      sequencing of the human genome and the design of more and more sophisticated
      technologies will largely influence the fields of pharmacology and toxicology.
      Thus, identification of new molecular targets, development of more powerful cell
      models, design of miniaturized and automated tests for high throughput screening
      of thousands of compounds synthesized by combinatorial chemistry and progress in
      genomic and proteomic technologies that permit simultaneous analysis of thousands
      of genes and their products, offer new investigative ways that will still widely
      be extended in the next future.

PMID- 11838951
TI  - The biological monitoring of toxic impacts on the environment.
AB  - The monitoring of the environment, for a long time confined to the analysis of
      some chemical products, today opens itself up to biological methods. The
      evaluation of the structure and functioning of the living communities within the
      ecosystem, the amount of pollution given off by the reactions of biochemical
      systems, and the toxic effects of chemical substances which allow biologists to
      estimate the diagnosis of the situation of the ecosystem. These tools are only
      now imposed to the member nations of the European Union through the water
      framework directive which has recently been published. This convergence between
      scientific advances and the needs of the environmental management opens the way
      for the development of biomonitoring technologies.

PMID- 11838952
TI  - Genetically modified plants: the stakes.
AB  - Generically modified plants (GMP) are massively used on the American continent in
      Australia and in China, since they represent an unquestionable potential for
      progress. New attributes are therefore devoted to the human and animal diet, to
      the facilitating of culture management, to the reducing of the chemical
      fertilizer and pesticide usage, and to the conquest of new cultural spaces.
      Considering itself to be flawed by a too hasty plunge into the market,
      concomitant with sagging evaluations of other innovations, Europe is confronted
      by a strong societal debate which blocks GMP cultures and orientates the research
      towards an evaluation of the environmental and public health risks and an
      evaluation of their economical and sociological impacts. The authors encourage
      this societal debate in order to arbitrate the presence of transgenes in
      conventional productions and products, to define the accepted rules of
      responsibility, to decide what is not acceptable, and to involve the more
      upstream actors and operators of the innovation process, all that keeping in mind
      the agronomical, ecological and economical repercussions of their decisions.

PMID- 11838953
TI  - Identity, traceability, acceptability and substantial equivalence of food.
AB  - The numerous food crises that Europe has experienced during the past five years
      have raised new consumer demands concerning the characterization, traceability,
      and safety of foods which are proposed on the market. The consumer has, at the
      same time, vigorously placed into question the modes of agricultural production
      in industrialized countries, as well as the structures and means of evaluating
      the food risks and the conditions of the consumer's participation in the public
      debate in these domains. For certain groups of consumers, one also attends a
      contestation of the expertise and the application to the food domain of the
      considerable progress that has taken place in the field of biotechnology. So it
      is that the development of genetically modified organisms (mainly plants, the raw
      material of food products) has experienced a slowing down in the European Union.
      The answers afforded to these new exigencies of consumers in matter of identity,
      traceability, and acceptability of the foods are dealt with in this paper, as
      well as the elements which may concur with the evaluation of their safety. The
      positive role that biotechnology can afford to the different domains is
      emphasized. A source of uneasiness, biotechnology is also a powerful tool for
      ameliorating the evaluation of the sanitary risks and for answering the hopes of
      the citizen in the food domain.

PMID- 11838955
TI  - Living things, the human genome, and patents.
AB  - For many years, patents and living things have not gotten along well in people's
      minds; nevertheless, patents are a real right. Even though people accept that a
      farmer can own a cow or that a Parisian can own a dog, they do not seem to
      understand that it is possible to patent a recombinant micro-organism or a DNA
      sequence. This is probably because industrial property is a hybrid concept, which
      mixes rights and science. Thus, this field is prone to misunderstanding by
      scientists and jurists, because of its juridical aspects for the former and
      because of its scientific aspects for the latter. The general public,as a result
      has two avenues of extravagant questioning to follow and consider. Finally, if
      industrial property is applied to a living phenomenon, it is often almost
      impossible to explain in layman's terms the ins and outs of the problems that may
      arise.

PMID- 11838954
TI  - The future of transgenic plants in developing countries.
AB  - Whatever their own policies may be, developing countries will inevitably be
      affected by the development of genetically-modified organisms in industrialized
      countries. While maintaining a cautious attitude, most of these countries wish to
      keep their options open, thus protecting themselves from the risk of being
      deprived of future technologies that might allow them to achieve self-sufficiency
      in food production, to resolve certain problems confronting their most vulnerable
      populations and to preserve the international competitiveness of their products.
      Companies should see that it is in their interest to help these countries
      implement their own policies, notably through an open attitude to industrial
      property. If the value of genetic engineering is thus confirmed, then it perhaps
      in this manner that GMOs will earn the legitimacy required to make them
      acceptable to the people of Northern countries where the majority of solvent
      markets are located.

PMID- 11838956
TI  - Biotechnology and human rights.
AB  - Biotechnology permits our world to progress. It's a tool to better apprehend the
      human being, but as well to let him go ahead. Applied to the living,
      biotechnologies present the same finality. But since their matter concerns
      effectively the living, they are the sources of specific dangers and particularly
      of that one to use the improvements obtained on the human to modify the human
      species. The right of the persons has to find its place to avoid that the
      fundamental rights of the human personality shall undergo harm. This mission
      assigned to the right of the persons is as so much invaluable that the economical
      stakes are particularly important in the domain of the biotechnologies.

PMID- 11838957
TI  - Some recent results on HIV pathogenesis with implications for therapy and
      vaccines.
AB  - In the third decade of AIDS research, we are still facing most of the challenges
      that emerged when the disease was characterized. While therapeutic approaches to
      control HIV infection are available in developed countries, novel principles to
      combat and prevent HIV infection are needed, due to the high cost and the
      negative effects of currently available drugs. In addition, it is now clear that
      this disease cannot be eliminated without a vaccine, which appears to be the only
      possible weapon to combat HIV in developing countries. We have focused on two
      approaches to fight HIV; one based on select members of a family of proteins,
      i.e. beta-chemokines, that we have show to interfere with HIV entry and
      replication, and another centered on a viral protein, HIV-1 Tat, that is
      crucially involved in HIV regulation and in some of the pathogenic manifestations
      of HIV infection. Studies from others and ourselves have shown that these two
      approaches are now ready to the leave experimental bench and move into clinical
      testing.

PMID- 11838958
TI  - Down-regulation of cell adhesion molecules LFA-1 and ICAM-1 after in vitro
      treatment with the anti-TNF-alpha agent thalidomide.
AB  - The tumor necrosis factor-alpha (TNF-alpha) inhibitor thalidomide is known to be
      a potent modulator of host immunity, a potential treatment for autoimmune
      disorders such as rheumatoid arthritis (RA) and a treatment for complications of
      HIV-1 infection. RA is an autoimmune disease of the joints that has been
      associated with hyperactivity of lymphocytes and other leukocytes, over
      expression of pro-inflammatory cytokines (TNF-alpha and IL-1) and chronic
      debilitating inflammation. Thalidomide may play a role in RA treatment by
      altering leukocyte function through down-modulation of cell adhesion molecules
      necessary for leukocyte migration to inflammatory sites. The present study
      investigates down-regulation of cell adhesion molecules (ICAM-1 and LFA-1) and
      decreases in cell-cell contacts between human T leukemic (CEM) cells and human
      umbilical vein endothelial cells (HUVEC) after thalidomide exposure. CEM cells
      were cultured in RPMI 1640 medium with 0, 10 or 50 microg/ml thalidomide, stained
      with fluorescent monoclonal antibodies specific to ICAM-1 and LFA-1 and
      expression was measured with flow cytometry. For cell-cell adhesion measurements,
      monolayers of HUVEC cultured in Kaign's F-12 medium were incubated with
      thalidomide treated CEM cells stained with calcein AM. Specific cell adhesion
      between the two cell types was visualized with fluorescence microscopy.
      Thalidomide treatment significantly reduced cell adhesion molecule expression in
      a dose-dependent fashion and inhibited HUVEC/CEM cell adhesion. These data
      support the hypothesis that thalidomide has modulatory actions on leukocyte
      functions through expression of cell adhesion molecules.

PMID- 11838959
TI  - Salmonella-mediated mucosal cell-mediated immunity.
AB  - Oral immunization with the recombinant Salmonella typhimurium strain (BRD 847)
      expressing the C fragment of tetanus toxin (TT) induces brisk Ag-specific mucosal
      S-IgA and serum Ab responses characterized by strong IgG2a Abs to the encoded
      antigen. We have constructed an attenuated Salmonella typhimurium (aroA- aroD-)
      strain that expresses chicken egg albumin (OVA) to further elucidate the role of
      Salmonella-induced Th1 cell phenotype on mucosal cell-mediated immunity (CMI).
      Peyer's patches and spleen lymphocytes from mice that received the oral
      Salmonella-OVA vaccine showed dramatic increases in the percent cell lysis of the
      H-2b restricted EG7.OVA tumor cell line. These results indicate that a single
      dose of rSalmonella vaccine antigen vector is required to illicit systemic and
      mucosal Th1-type responses and CTLs. These results also support the existence of
      a highly regulated relationship between specific cell-mediated immunity and a
      branch of the humoral immune system, i.e. mucosal IgA responses.

PMID- 11838960
TI  - Survival of AIDS according to injecting drug use among Puerto Rican AIDS
      patients.
AB  - This paper aims to: 1/ describe IDU's and non-IDU's according to age, gender,
      AIDS criteria and antiretroviral therapy; and 2/ assess survival differences
      between IDU's and non-IDU's according to age, gender, AIDS diagnosis criteria and
      antiretroviral therapy. This study is a survival study of a longitudinal cohort.
      The sample was composed of 1,258 AIDS patients of a cohort of HIV-infected adults
      who sought medical care at either the Immunology clinic of Bayamon or the Ramon
      Ruiz Arnau University Hospital between 1992 and 1999. The variables studied were:
      survival time of AIDS, intravenous drug use, age, gender, AIDS defining criteria
      and antiretroviral therapy (yes/no). The results have been that IDU's had lower
      survival than non-IDU's. Significant differences in the survival functions (IDU's
      vs non-IDU's) were found among male patients, older patients, patients with
      immunological criteria and patients with antiretroviral therapy. The survival
      among these variables was lower in IDU's than non-IDU's. This study suggested
      that decreased survival of IDU's may be related to later diagnosis and decreased
      access to drug therapy. Clinical endeavors should take into consideration the
      variables related to IDU's survival to develop health programs in order to
      enhance the quality of life and the survival of the AIDS patients.

PMID- 11838961
TI  - Cyclin levels during TNF-alpha-induced apoptosis in HIV-infected cells.
AB  - Cyclins are cell cycle regulatory proteins. We compared the concurrent kinetics
      of apoptosis and cyclin expression between HIV-infected cells (J1.1), and
      uninfected Jurkat cells. Cells were cultured with TNF-alpha and harvested at 24,
      48 and 72 hr to examine cyclin expression and DNA content. We found a decline in
      the levels of the mitotic B cyclin in Jurkat cells (16 to 2%, 48 hr), while in
      J1.1 cells it was observed in cyclin E (60 to 37%, 72 hr). Because cyclin B is
      mitotic, results suggest that Jurkat cells undergo apoptosis at G2, while J1.1
      cells enter mitosis and then die by apoptosis, as no changes in cyclin B or DNA
      content at G2M were observed. G1 cyclin E decline in J1.1 cells also suggests
      that they die after entering mitosis. Based on differences in the cyclins
      involved, it seems that HIV-1 manipulates the cell cycle to protect J1.1 cells
      from apoptosis induction at G2, a critical cell cycle phase for HIV replication.
      Thus, cyclins are useful to characterize points in the cell cycle at which
      apoptosis is induced, and could become excellent tools to evaluate mechanisms of
      action of antiretroviral drugs in the cell cycle of HIV-infected cells.

PMID- 11838962
TI  - Pulmonary tuberculosis mortality risks in a cohort of HIV/AIDS patients in Puerto
      Rico.
AB  - Pulmonary tuberculosis (TB) has re-emerged in relation to the HIV epidemic. To
      gain knowledge of TB infection in HIV-infected patients, we studied 106 HIV-TB
      cases in a cohort of 2,646 patients in Puerto Rico between January 1992 and
      September 1999. The TB prevalence was 4%; 82% were males and 73.6% were injecting
      drug users (IDU). At the time of TB diagnosis, the mean CD4+ T-cell count was
      174/mm3, 35% were in antiretroviral treatment and 42.5% had another AIDS related
      condition. Only 9% received two or more antiretroviral medications. The death
      rate in the first year after the TB diagnosis was 55%. A Cox proportional hazard
      analysis showed that CD4+ T-cells <200/mm3 (p<0.01), history of toxoplasmosis
      (p<0.01), wasting syndrome (p<0.01) and lack of antiretroviral treatment (p=0.12)
      increased their mortality risk. The studied patients had a highly compromised
      immune system at the time of TB diagnosis. Low CD4+ T-cells (essential to control
      the TB infection) significantly increased the hazard and mortality risk of the
      cases studied. Early antiretroviral therapy in combination is recommended in HIV
      infected patients, particularly in those with IDU, TB history and low CD4+ T-cell
      levels, to ensure an optimal immune system function that limits the pulmonary TB
      morbidity and mortality.

PMID- 11838963
TI  - The usefulness of defined clinical features in the diagnosis of HIV/AIDS
      infection in Sierra Leone.
AB  - Sierra Leone ranks at the bottom of the global World Bank Development Index based
      on multiple health and economic indices and lacks the resources to purchase HIV
      diagnostic kits. Our study has defined some common clinical features presenting
      HIV infection that could form clinical algorithms for the diagnosis and
      recognition of HIV infection by health workers in Sierra Leone. In a private
      clinic in Freetown, Sierra Leone, West Africa, 106 out of a total of 124 patients
      presenting with various symptoms and strong clinical suspicion of HIV infection
      within a two-year period (1999 and 2000), were deemed positive by two different
      ELISA tests. The prevalence of HIV infection seen in this private clinic in
      Freetown in 2000 was 14.89% as compared to 9.25% in 1999. The positive predictive
      value of our clinical diagnosis of HIV/AIDS infection was 85.5%. The male:female
      ratio of the patients in our series was 1:1.9, with a mean age of 39 years for
      males and 28 years for females. HIV infection was found in a cross-section of the
      population that we examined. Heterosexual contact appeared to be the major mode
      of transmission amongst our patients and there seemed to be a significant
      epidemiological risk of HIV infection amongst those who traveled to other
      countries in the West African sub region. Common clinical features in decreasing
      frequency were fever (92.5%), weight loss (84.1%), lymphadenopathy (78.3%), cough
      (48.1%), diarrhea (37.7%), candidiasis (32.1%) and body aches (30.1%).

PMID- 11838964
TI  - The temperature sensitive mutant p53-143ala extends in vitro life span, promotes
      errors in DNA replication and impairs DNA repair in normal human oral
      keratinocytes.
AB  - Many human cancers contain a hemizygous point missense mutation in p53, allowing
      expression of both wild-type and mutant p53. To understand the relationship
      between wild-type and mutant p53 in cells, we investigated the influence of a
      naturally occurring temperature-sensitive mutant p53 (valine to alanine
      substitution at codon 143: mp53-143ala) on the life span of normal human oral
      keratinocytes (NHOK) and the expression of wild-type p53. We also investigated
      the effect of the mutant p53 on the genetic stability of NHOK. The mp53-143ala
      extended the in vitro life span of NHOK by four-fold, but failed to overcome the
      M2 crisis stage for immortalization. The mp53-143ala notably suppressed wild-type
      p53 in NHOK at post-transcriptional levels. Moreover, the mp53-143ala notably
      increased both spontaneous and genotoxic agent-induced mutation frequency of a
      shuttle vector in NHOK. These data indicate that mutant p53 induces genetic
      instability by, in part, inhibiting the expression of wild-type p53 through a
      dominant negative role in cells expressing both mutant and wild-type p53.

PMID- 11838965
TI  - MHC class II proteins contain a potential binding site for the verotoxin receptor
      glycolipid CD77.
AB  - Globotriaosyl ceramide or CD77 functions as a cell surface receptor for toxins of
      the Shiga toxin/verotoxin family and as a marker for germinal center stage B
      cells. The B-cell protein CD19 and the interferon-alpha receptor possess
      verotoxin-like amino acid sequences in their extracellular domains, and CD77 has
      been shown to function in CD19-mediated adhesion and interferon-induced growth
      inhibition. The Burkitt's lymphoma cell line, Daudi, is similar to germinal
      center B-cells in their expression of CD77, CD19 and MHC class II molecules.
      Using the multiple sequence alignment program, ClustalW, we have identified a
      verotoxin-like amino acid sequence on the beta-chain of human and murine MHC
      class II molecules. Binding of CD77 at this site could modulate the peptide
      binding properties of these MHC class II molecules. Using Western blot analysis
      of whole cell extracts, we found that CD77-positive Daudi cells have higher
      levels of HLA-D proteins than VT500 cells, a Daudi-derived CD77-deficient mutant
      cell line. In contrast, MHC class II-mediated adhesion and surface expression are
      similar in the two cell lines. Therefore, CD77 could play a functional or
      regulatory role in MHC class II-mediated functions specifically relating to
      antigen presentation by B-cells to T helper cells.

PMID- 11838966
TI  - TSG101 expression in gynecological tumors: relationship to cyclin D1, cyclin E,
      p53 and p16 proteins.
AB  - Recent studies have shown that in vitro steady-state expression of the tumor
      susceptibility gene TSG101 is important for maintenance of genomic stability and
      cell cycle regulation. To determine the contribution of TSG101 expression in
      neoplastic formation, expression of TSG101 protein levels were evaluated in
      primary ovarian and endometrial adenocarcinoma tumors. Expression of TSG101 was
      also examined in various tumor cell lines (PA-1, AN3CA, HeLa, HS578T, HCT116).
      Full-length TSG101 protein was detected in these tumors and cell lines indicating
      that intragenic deletions were not characteristic of TSG101. In addition, TSG101
      protein levels were compared with aberrations of prominent cell cycle regulatory
      molecules such as cyclin D1, cyclin E, p16 and p53. Reduced TSG101 protein was
      observed in 36% (8/22) of ovarian and 17% (1/6) of endometrial adenocarcinoma.
      Aberrant levels of p53, p16, cyclin D or E were comparable to published studies
      indicating that the clinicopathological distribution of these cases did not favor
      advanced stage tumors. Altogether, these findings suggest that a down-regulation
      of TSG101 is associated with tumorigenesis in a subgroup of gynecological tumors.

PMID- 11838967
TI  - Comparison of adhesion mechanisms and surface protein expression in CD77-positive
      and CD77-negative Burkitt's lymphoma cells.
AB  - The Burkitt lymphoma-derived Daudi cell line is often used as an in vitro model
      for germinal center B-cell function. Globotriaosyl ceramide (CD77), a marker for
      germinal center B-cells, is present on Daudi cells but is deficient in the Daudi
      derived mutant VT500 cell line. Previous results showed a correlation in these
      cells between CD77 expression and expression of the B-cell protein CD19 and
      indicated that CD19/CD77 interaction is a mechanism for B-cell adhesion. Roles
      for CD77 in IFN-alpha-induced growth inhibition and anti-viral activity also have
      been described previously. Through flow cytometric analysis and adhesion assays,
      we investigated whether expression of CD77 was required for cell adhesion
      pathways induced by IFN or antibodies against additional B-cell surface
      molecules: CD20, CD22, CD38, CD40, CD81 and HLA-D proteins. In contrast to the
      pronounced homotypic adhesion induced by treatment with interferon-alpha in Daudi
      cells, no increase in adhesion was observed in IFN-treated VT500 cells. Of the B
      cell proteins tested, only CD22-mediated adhesion and surface expression was
      stronger in Daudi than in VT500 cells. These results indicate that CD77 may be
      required for IFN and CD22-associated adhesion pathways, but CD77 is not a
      universal component of adhesion pathways in these cells.

PMID- 11838968
TI  - Modelling viral and CD4 cellular population dynamics in HIV: approaches to
      evaluate intervention strategies.
AB  - Computational models, such as in epidemiology, provide a powerful tool that can
      be used to systematically examine an array of dynamic interactions among
      populations as well as to evaluate altemate disease intervention strategies. The
      specific objectives in this study were to: a/ examine the interaction of cellular
      (CD4) and HIV population dynamics and evaluate the impact of the use of
      combination chemotherapies on viral and CD4 populations (Experiment #1), b/
      demonstrate how modelling can be used to evaluate the impact of an intervention
      (condom use) on reducing the rate of HIV/AIDS (Experiment #2). In this study, we
      used state transition models and conducted simulation experiments to evaluate
      various alternatives for the control and/or prevention of HIV/AIDS. The result
      indicated that combination therapy (double or triple drug therapies) was very
      effective. The HIV viral population decreased rapidly and remained suppressed for
      years. On the other hand, the CD4 cell population increased above 400 cells per
      ml and was maintained above that level for many years. Mono-therapy was not as
      effective; although the viral load decreased rapidly, it increased to its
      original levels within a few months. Since condom use is one of the key
      interventions of HIV/AIDS, we evaluated its use in 25%, 50% and 75% of an adult,
      sexually active population. Increasing condom use by 50% and 75% above an
      estimated baseline of 25% reduced the incidence of AIDS by 53% in Blacks, 49% in
      Hispanics and 43% in Whites. The study shows how a cellular/molecular level model
      can be incorporated within a macro-epidemiologic systems dynamics model to
      evaluate a variety of scientific questions such as to see if cellular/molecular
      level interventions reduce morbidity and mortality rates in HIV.

PMID- 11838969
TI  - Ethnic disparities in care following acute coronary syndromes among Asian
      Americans and Pacific Islanders during the initial hospitalization.
AB  - Despite the fact that Asian Americans and Pacific Islanders are the fastest
      growing minority population in the United States, little is known about their
      treatment patterns and outcomes, particularly for Asian American and Pacific
      Islander sub-groups. Multivariable logistic regression was used to compare
      differences in revascularization and mortality rates following acute coronary
      syndromes among Asian American and Pacific Islander sub-groups [Japanese (n =
      1342), Chinese (n = 249), Filipino (n = 314), Native Hawaiian (n = 361)) and
      Caucasians (n = 569)] during the initial hospitalization using administrative
      (claims) data from 1997 to 1999. Analyses were stratified by gender and
      controlled for age, diabetes mellitus, congestive heart failure, acute myocardial
      infarction, ACG morbidity level and system of care. We found that the type of
      procedures received during the initial hospitalization differed according to
      patient ethnicity for male patients but not for female ones. Compared to
      Caucasians, male Asian Amercian and Pacific Islanders patients were less likely
      to undergo percutaneous coronary interventions and more likely to undergo
      coronary artery bypass graft surgery. In the future, a more comprehensive
      outcomes study is needed, to examine the impact of any interethnic differences in
      revascularization rates on intermediate and long-term mortality, patient
      satisfaction, and self-reported functioning and well-being. The trend toward
      higher mortality following acute coronary syndromes among Asian Americans and
      Pacific Islander males emphasizes the importance of such a study.

PMID- 11838970
TI  - Quantification of amino acid enantiomers in single cells by capillary
      electrophoresis.
AB  - An analytical method is described to quantify amino acid enantiomers in single
      cells. Cellular samples were derivatized with a fluorescence tagging reagent,
      naphthalene-2,2-dicarboxaldehyde, in a mini-volume (4 microl) prior to
      separation. Enantiomeric resolution was achieved by beta-cyclodextrin modified
      micellar electrokinetic chromatography. The separation was coupled with laser
      induced fluorescence detection. The method had a detection limit of 0.1 microM
      for aspartic acid enantiomers (1.0 microl sample solution was derivatized).
      Single neurons isolated from the five major ganglia of Aplysia californica were
      analyzed to determine the D/L enantiomeric ratios of aspartic acid, phenylalanine
      and leucine. D-aspartic acid was found at high levels in many neurons tested and
      its cellular distribution was highly heterogeneous.

PMID- 11838971
TI  - Familial systemic lupus erythematosus: a comparison of clinical manifestations
      and antibody presentation in three ethnic groups.
AB  - The serologic and clinical features of patients from pedigrees multiplex for
      systemic lupus erythematosus (SLE) were evaluated among three ethnic groups:
      Hispanics, African-Americans and European-Americans. Data were obtained from a
      registry of 123 pedigrees, composed of 4 Hispanic, 40 African-American and 79
      European-American pedigrees. All patients met at least four criteria for the
      diagnosis of SLE per the American College of Rheumatology. Clinical information
      was obtained through review of the medical records and questionnaires completed
      by the participants. Ethnicity by self-identification was found to be an
      important factor influencing the prevalence of serologic results and clinical
      features. Anti-nRNP occurred more frequently in African-Americans (45.7%) than in
      European-Americans (7.5%) or Hispanics (0%) (p<0.0000001), as did anti-Sm (18.5%
      vs 1.6% and 0%, respectively) (p<0.000001). Malar rash, photosensitivity and oral
      ulcers were most frequent in the Hispanic population while proteinuria and
      leukopenia predominated in the African-American population. Arthritis and
      lymphopenia were present in a similar proportion in all ethnic groups. These
      results show that many of the ethnic differences known for isolated cases of SLE
      are also present in familial cases of SLE.

PMID- 11838972
TI  - Identification of genes expressed in the Xenopus inner ear.
AB  - Recent studies indicate that hearing loss in humans has strong hereditary
      components associated with expression of specific genes in the auditory apparatus
      of the inner ear. However, the inner ear poses challenges for molecular research
      because the amount of tissue that can be isolated is limited, and extraction
      procedures yield small quantities of RNA and protein. To begin to identity genes
      essential for auditory function, we synthesized a cDNA library using an RT-PCR
      protocol and total RNA isolated from eight Xenopus laevis inner ears. Sequence
      analysis of randomly selected clones demonstrated expression of both identified
      (calmodulin, SNARE protein, syndecan-2) and unidentified genes, and confirmed
      synthesis of full length transcripts. Confocal and scanning electron microscopy
      (SEM) were used to examine the structure of inner ear organs that serve as
      auditory receptors in amphibians: the sacculus, the amphibian papilla and the
      basilar papilla. SEM images illustrate the heterogeneity of bundle morphology and
      demonstrate the continuous appearance of stereociliary bundles in the X. laevis
      amphibian papilla during larval development and adult life. Investigations of
      gene expression in Xenopus auditory organs using clones recovered from inner ear
      cDNA libraries should provide insight regarding the molecular basis of hearing.

PMID- 11838973
TI  - Suspension array technology: new tools for gene and protein analysis.
AB  - Flow cytometry has long been a key tool in the analysis of lymphocytes and other
      cells, owing to its ability to make quantitative, homogeneous, multiparameter
      measurements of particles. New developments in illumination sources, digital
      signal processing and microsphere chemistry are driving the development of flow
      cytometry in new areas of biomedical research. In particular. the maturation of
      approaches to perform highly parallel analyses using suspension arrays of
      microspheres with different morphospectral features is making flow cytometry an
      important tool in protein and genetic analysis. In this paper, we review the
      development of suspension array technology (SAT), current applications in protein
      and genomic analysis, and the prospects for this platform in a variety of large
      scale screening applications.

PMID- 11838974
TI  - N-alkyl-3-decarboxy-3-hydroxymethylsiastatin B, a new family of glycosidase
      inhibitors of gem-diamine 1-N-iminosugars.
AB  - N-Alkyl-3-decarboxy-3-hydroxymethylsiastatin B, N-alkyl analogues of gem-diamine
      1-N-iminosugars, is a new family of glycosidase inhibitors that have been
      synthesized from siastatin B isolated from Streptomyces culture. These compounds
      were evaluated as glycosidase inhibitors.

PMID- 11838975
TI  - Chemistry of plants from Crete: stachyspinoside, a new flavonoid glycoside and
      iridoids from Stachys spinosa.
AB  - The new flavonoid glycoside stachyspinoside (1), and the three iridoids, 7-O
      acetyl-8-epi-loganic acid (2), ajugol (3) and harpagide (4) were isolated from
      Stachys spinosa. The structures of these compounds were established on the basis
      of mass spectrometry (ESMS and tandem MS), one- and two-dimensional nuclear
      magnetic resonance experiments (COSY, COSY LR, HMQC, TOCSY and HMBC) as well as
      simple chemical derivatization.

PMID- 11838977
TI  - Total synthesis of (+/-) tanikolide.
AB  - The natural polyketide (+/-)-tanikolide (1) was prepared in eight steps starting
      from hex-5-enol. Key steps in this synthesis are a Sharpless dihydroxylation and
      a Grignard reaction between an alkyl halogenide and a ketone. The lactonization
      occurred spontaneously during the oxidation of the primary alcohol function to
      the carboxy group.

PMID- 11838976
TI  - Minor diterpenoids from Halimium viscosum.
AB  - Two new diterpenic acids with an ent-halimane skeleton have been isolated from
      the aerial parts of Halimium viscosum (Villarino de los Aires chemotype) and
      separated as methyl esters. These diterpenes were 13-oxo-14, 15-dinor-1(10),11E
      ent-halimadien-18-oic acid and 15-hydroxy-1(10),13Z-ent-halimadien-18-oic acid.

PMID- 11838978
TI  - BI- and tricyclic diterpenoids from Halimium viscosum.
AB  - The study of the acid and neutral parts of the n-hexane extract of Halimium
      viscosum (S. Joao da Pesqueira, Portugal) has led to the isolation of various
      known diterpenoids with the ent-halimane skeleton. Five new compounds have now
      been isolated, one with the ent-halimane skeleton, and four with the valparane
      skeleton, two of them with the valparane skeleton degraded. The structures of
      these compounds, determined by spectroscopic methods using 2D experiments (1H
      13C, HMQC and HMBC), were dimethyl 1(10)-halimen-15,18-dioate, dimethyl 3,19
      dinor-15-valparen-2,4-dioate, methyl 16-nor-2,3-secovalpara-3,15-dioxo-2-oate,
      1,3,5,1 5-valparatetraene and 3R-4alpha-methoxy-15-valparen-2-one.

PMID- 11838979
TI  - Homarine, a common metabolite in edible Mediterranean molluscs: occurrence,
      spectral data and revision of a related structure.
AB  - Homarine was isolated from nine edible species of marine molluscs belonging to
      classes Gastropoda, Bivalvia, and Cephalopoda. A thorough chromatographic, NMR
      and MS study provided evidence that homarine is a common and abundant metabolite
      of all these species. This study casts doubt on a previous assertion that 1,1'
      dimethyl-[2,2']-bipyridinium is a metabolite of the Bivalve Callista chione.

PMID- 11838980
TI  - Isolation and structure determination of a new sesquiterpene lactone from
      Nauplius aquaticus.
AB  - The aerial part of Nauplius aquaticus afforded a new sesquiterpene lactone with a
      humulanolide skeleton, 6,7,9,10-tetrahydroasteriscunolide (1), in addition to the
      known asteriscunolides A (2) and D (3). Their structures were established
      principally by two-dimensional NMR spectroscopy.

PMID- 11838981
TI  - Two new labdane diterpene glycosides from flowers of Baccharis medullosa DC.
AB  - From the flowers of Baccharis medullosa DC (Asteraceae) two new ent-labdane-type
      diterpene glycosides were isolated. Structures were established by application of
      various spectroscopic techniques. The sugar residues were identified after acid
      hydrolysis of the isolated products.

PMID- 11838982
TI  - Daphwazirin, biscoumarin glycopyranoside from Daphne oleoides.
AB  - Daphwazirin, a new biscoumarin glycoside (1), along with four known compounds
      (2), (3), (4) and (5) has been isolated from the roots of Daphne oleoides. Its
      chemical structure is established as 7-hydroxy-8-[2-oxo-2H-1-benzopyran-7'-(O
      alpha-L-rhamnosyl)-6'-yl]-2H-1-benzopyran-2-one through spectroscopic techniques
      and chemical analysis.

PMID- 11838983
TI  - One step conversion of toxic beta-asarone from Acorus calamus into 1-(2,4,5
      trimethoxyphenyl)-1,2-dihydroxypropane and asaronaldehyde occurring in Piper
      clusii.
AB  - 1-(2,4,5-Trimethoxyphenyl)-1,2-dihydroxypropane (2), a natural phenylpropanoid
      occurring in Piper clusii, has been synthesized for the first time from toxic
      beta-asarone (1) of Acorus calamus with osmium tetroxide, while 1 with osmium
      tetroxide (catalytic amount) in presence of sodium metaperiodate furnished the
      asaronaldehyde (3) in high yield.

PMID- 11838984
TI  - Allelopathic agents from Cyrtocymura cincta.
AB  - The sesquiterpenoid fractions from the chloroform extracts of roots and aerial
      parts of the weed Cyrtocymura cincta (Griseb.) H. Robinson (Compositae) were
      tested to observe the effects on seed germination and growth of three dicot and
      four monocot species. Promotion and inhibition effects were observed according to
      the examined compound, specific seed or cultivar, and concentration.

PMID- 11838985
TI  - Physiologic changes of the cornea with contact lens wear.
AB  - PURPOSE: This article reviews the corneal changes resulting from the hypoxia that
      occurs during sleep and specifically during contact lens wear. METHODS:
      Discussion includes a literature review and observations regarding the changes to
      the corneal epithelium, stroma, and endothelium that take place during sleep and
      wearing of contact lenses made from different materials. RESULTS: Hypoxia and
      hypercapnia cause significant changes to the corneal epithelium, stroma, and
      endothelium. Some of these changes can also be seen following the sleep cycle.
      Epithelial changes include decreased metabolic rate, morphologic changes,
      microcysts, changes in junctional integrity, decreased corneal sensation, and
      pannus formation. Stromal changes include stromal edema, stromal acidosis,
      neovascularization, and changes in corneal shape and, ultimately, corneal
      thinning. Endothelial changes include bleb formation, polymegethism, changes in
      endothelial cell density, and possible changes in endothelial function.
      CONCLUSIONS: There are multiple and significant corneal changes resulting from
      hypoxia and hypercapnia. These changes vary with the specific lens style. The
      high-oxygen-permeable contact lenses recently introduced may overcome some of
      these problems.

PMID- 11838986
TI  - Spontaneous globe luxation associated with contact lens placement.
AB  - PURPOSE: Globe luxation, characterized as the anterior dislocation of the eyeball
      beyond retracted lids, presents a dramatic clinical picture. It is an uncommon
      event and can produce anxiety in both the patient and the physician. The purpose
      of this article is to present a case of spontaneous globe luxation which occurred
      with attempted contact lens placement. METHODS: A case report and literature
      review are presented. RESULTS: Manual reduction of the globe required conscious
      sedation in the emergency room. Diffuse superficial punctate keratitis resolved
      completely with no visual sequelae. DISCUSSION: The clinical features,
      epidemiology, risk factors, complications and treatments of globe luxation are
      presented. Eye care specialists who fit and dispense contact lenses should be
      aware of risk factors associated with globe luxation. A step-wise plan for
      management is presented, in hope of limiting patient discomfort, recurrence, and
      perhaps long-term visual impairment.

PMID- 11838987
TI  - Contact lenses in the correction of childhood aphakia.
AB  - PURPOSE: To evaluate the results of extended-wear silicone contact lenses
      (Silsoft, Bausch & Lomb, Rochester, NY, U.S.A) after congenital cataract
      extraction. METHOD: Case records of congenital cataract extraction performed
      between 1992-1999, in the Department of Ophthalmology, Dokuz Eylul University
      School of Medicine, were retrospectively reviewed. Convenient-power extended-wear
      silicone contact lenses (Silsoft) were prescribed for patients 5 to 12 days after
      surgery. Patients were scheduled for follow-up control visits once per month in
      the first year, bimonthly in the second year, and quarerly visits thereafter.
      Visual acuity, fixation, binocularity, and deviation were checked at each follow
      up visit. Examination of the cornea and the contact lens surface was also
      performed at each visit. RESULTS: A total of 51 children (83 eyes) were included
      in the study. Mean age was 19.4 +/- 18 months. Mean duration of contact lens wear
      per lens was 26 +/- 11 weeks. Contact lens wear was discontinued for 11 eyes: 6
      because of unstable lens, frequent loss, and financial problems, and 5 were
      discontinued because of recurrent irritation and corneal infiltration. Mean
      contact lens usage time per patient was 5.8 years, and mean contact lens loss was
      0.98 per year. Visual acuity improved in 58 (69.8%) eyes and remained unaltered
      in the remaining 25 eyes. CONCLUSION: Extended-wear silicone contact lenses offer
      a safe, easy treatment option for childhood aphakia, providing prolonged wearing
      time and low rates of complications and drop out.

PMID- 11838988
TI  - Corneal endothelial polymegethism and pleomorphism induced by daily-wear rigid
      gas-permeable contact lenses.
AB  - PURPOSE: To determine if there are any corneal endothelial cell size and shape
      changes (and the time course of these changes) in subjects wearing rigid high gas
      permeable (RGP) contact lenses for daily wear. METHODS: Ninety-seven eyes of 57
      new wearers were fitted with a fluoroperm contact lens material (Persecon92E,
      oxygen transmissibility (Dk)= 92 x 10(-11)). Prior to lens wear and after 1 week,
      1 month, 3 months, 6 months, and 1 year, noncontact endothelial photographs were
      taken. Maximum cell size/Minimum cell size (Max/Min) was measured as an index of
      polymegethism and the relative frequency of 5-, 6-, and 7-sided cells was
      evaluated. RESULTS: An increase in the ratio of Max/Min was present 1 week after
      lens fitting and increased further over the subsequent year. This study showed
      significant increase in endothelial polymegethism and in the relative frequency
      of 7-sided cells, but a significant decrease in the relative frequency of 6-sided
      cells. CONCLUSIONS: Daily-wear high Dk gas-permeable contact lenses can cause
      endothelial polymegethism and pleomorphism similar to those caused by soft and
      hard contact lenses.

PMID- 11838989
TI  - Retained lens fragments in resident-performed cataract extractions.
AB  - PURPOSE: To investigate the incidence, management, and outcome of retained lens
      fragments following resident-performed cataract extraction. METHODS: A
      retrospective review of all eyes undergoing cataract extraction by the residents
      of Baylor College of Medicine over a 4-year time frame (July/95-June/99).
      RESULTS: A total of 3389 eyes underwent cataract extraction, and 26 patients
      (0.8%) required pars plana vitrectomy (PPV) for retained lens fragments. One or
      more vision threatening complications occurred in 19 (73%) of these patients. The
      most common complications were cystoid macular edema (CME) (8 eyes, 31%) and
      rhegmatogenous retinal detachment (RRD) formation (6 eyes, 23%). Additional
      surgical procedures were required for 9 (35%) eyes; the most common were repeat
      PPV, and placement of focal photocoagulation for diabetic macular edema (4 eyes
      per each procedure, 15%). Six-month follow-up was available for 16 eyes; of
      these, best-corrected visual acuity was 20/40 or better in 5 (31%) and 20/200 or
      worse in 7 (44%). The most common reasons for limited visual acuity were RRD (3
      eyes, 19%) and CME (3 eyes, 19%). CONCLUSION: In this retrospective series, the
      incidence of retained lens fragments following resident-performed cataract
      extraction was less than 1%. Significant complications, resulting in the need for
      additional surgical procedures, occurred in most of these eyes, and this was
      associated with limited visual function at final follow-up. Retention of lens
      fragments following resident-performed cataract extraction remains an infrequent
      yet serious complication associated with a guarded visual prognosis.

PMID- 11838990
TI  - Annexin V binding to rabbit corneal epithelial cells following overnight contact
      lens wear or eyelid closure.
AB  - PURPOSE: To determine the effects of open or closed eye and overnight contact
      lens wear on rabbit corneal epithelial surface cell death, detected by annexin V
      binding to cell surface phosphatidylserine and propidium iodide (PI) double
      labeling. METHOD: New Zealand white rabbits (n = 42) weighing 2.5 to 3.5 kg were
      divided into 7 study groups: hyper Dk/t rigid gas-permeable (RGP) lens; high Dk/t
      RGP lens; low Dk/t RGP lens; hyper Dk/t soft lens; high Dk/t soft lens; eyelid
      closure; and nictitating membranectomy study group (n = 6 rabbits for each
      group). Each rabbit was randomly chosen to have either one eye fitted with a test
      contact lens or both eyelids sutured closed; the contralateral eye served as a
      control. Rabbits were humanely sacrificed after 24 hours. Corneal buttons
      including the limbus were excised and stained with annexin V-FITC and PI to
      identify the number of nonviable epithelial surface cells. A series of sequential
      microscopic adjacent fields (200 microm X560 microm) from the inferior limbus to
      the central cornea were evaluated using epifluorescence microscopy, and the total
      number of cells stained with annexin V or PI, or both, was counted in each field.
      RESULTS: Nonviable cells (cells with positive staining) were lowest in density at
      the limbus and gradually increased in numbers towards the central cornea under
      normal open eye conditions (P<0.05). Eyelid closure (no lens) caused a
      significant decrease in the numbers of nonviable cells in the peripheral and
      central cornea (P<0.05) but not at the limbus (P>0.05). Overnight wear of hyper
      Dk/t or high Dk/t RGP soft contact test lenses caused significant decreases in
      the numbers of nonviable cells on the central corneal surface (P<0.05). Hyper
      Dk/t and high Dk/t soft lenses had similar suppressive effects on the number of
      surface nonviable cells, independent of lens oxygen transmissibility. By
      contrast, the number of nonviable cells was dependent upon RGP lens oxygen
      transmissibility; hyper Dk/t RGP lens wear produced significantly less
      suppression of the number of nonviable cells in the central cornea than high Dk/t
      RGP lens wear (P<0.05). Wear of a nonphysiologic low oxygen transmissible RGP
      test lens however, produced a significant increase in nonviable cells in the
      central cornea. The number of nonviable epithelial surface cells was not affected
      by nictitating membranectomy under open eye conditions (P>0.05). CONCLUSIONS:
      This study revealed in the rabbit model a gradient of nonviable surface
      epithelial cells increasing towards the central cornea under open eye conditions
      and with central suppression of surface cell death following closed eye (no lens)
      or physiologic contact lens wear. Taken together, the results suggest that eyelid
      closure or contact lens wear may protect the corneal epithelial cells against the
      shear stress forces exerted by eyelid blinking, which are believed to drive
      central epithelial surface cell death and exfoliation. However, under very low
      oxygen tensions combined with lens effect, such as in low Dk/t RGP lens wear,
      surface cell death may be accelerated.

PMID- 11838992
TI  - Results of combined myopic astigmatic LASIK treatment and retreatments.
AB  - PURPOSE: A study of combined LASIK treatment and retreatment results for both
      myopia and myopic-astigmatic correction. METHODS: Three hundred fifty-three
      consecutive eyes underwent LASIK surgery using the VISX Star excimer laser.
      Preoperative mean sphere was -6.37 +/- 2.93 D with mean cylinder of +1.01 +/- 0.9
      D. The initial refraction of the 40 patients needing retreatment was -7.42 +/-
      2.49 D with a mean cylinder of +1.0 +/- 0.61 D. RESULTS: Data were analyzed in
      the following way: Group I: Primary treatment (all); Group II: Group I excluding
      retreatment; Group III: Retreatment; and Group IV: Groups II and III combined.
      Postoperative uncorrected visual acuity (UCVA) data at 1, 3, and 6 months were:
      Group I: 20/40 or better 90.5%, 87.2%, and 89.5%; 20/20 or better 52.0%, 48.9%
      and 59.6%; Group II: 20/40 or better 95.0%, 95.2%, and 95.7%: 20/20 or better
      52.0%, 62.6% and 63.8%; Group III: 20/40 or better 97.5%, 97.5%, and 100%; 20/20
      or better 80%, 76% and 77%; and Group IV. 20/40 or better 97%; 20/20 or better
      63% at six months. Pretreatment degree-of-myopia comparison in Group I was (0-3
      D) 90% 20/20 UCVA after 6 months; (-6 - -9 D) 60% 20/20; and (> -12 D) 44% 20/20.
      Complications included 1 free flap, 1 partial flap, and 4 epithelial ingrowths.
      CONCLUSIONS: These results demonstrate myopic-astigmatic LASIK treatment to be
      safe, effective, and predictable in correcting myopia and associated
      astigmatisms. For patients requiring retreatment, results are excellent. Results
      should be reviewed after all treatments have been completed. The success rate for
      LASIK surgery seems to be directly related to the degree of myopia. As myopia
      increases, the chance of achieving 20/20 vision decreases.

PMID- 11838991
TI  - Nitric oxide levels in tears of patients with mild forms of papillary
      conjunctivitis induced by rigid gas-permeable contact lenses.
AB  - PURPOSE: To determine whether nitric oxide (NO) is detectable in the tear fluid
      of patients with mild forms of papillary conjunctivitis who wear rigid gas
      permeable contact lenses. METHODS: Tear samples were taken from 12 users of rigid
      gas-permeable contact lenses and 12 healthy controls. Samples were analyzed, and
      the levels of NO were determined. RESULTS: The mean level of NO in those who wore
      contact lenses was 118.98 micromol/L (95% CI: 91.85-146.10 micromol/L); whereas
      the level of NO found in the control subjects was 114.84 micromol/L (95% CI:
      102.54-127.14 micromol/L). The difference was statistically insignificant
      (P>0.05). CONCLUSION: Nitric oxide levels in the tear fluid of rigid gas
      permeable contact lens users did not correlate with the presence of mild symptoms
      of papillary conjunctivitis.

PMID- 11838993
TI  - A metallic foreign body presenting in the anterior chamber angle.
AB  - PURPOSE: This article describes a case in which a patient presented with a
      previously undetected metallic foreign body in the anterior chamber angle.
      METHODS AND RESULTS: A 42-year-old Hispanic man presented with a 5-day history of
      foreign-body sensation and redness in his left eye. He had been using a hand saw
      without safety glasses 2 days before the onset of his initial symptoms. Physical
      examination revealed a metallic foreign body embedded in the inferior angle of
      his left eye. Surgical removal of the foreign body was performed, and the patient
      remains well 1 year after surgery. CONCLUSIONS: All physicians should maintain a
      high degree of clinical suspicion for intraocular foreign bodies when presented
      with a patient who may have sustained ocular trauma. All eye-care providers need
      to emphasize the need for proper eye protection to patients who engage in high
      risk activities that may lead to penetrating ocular trauma.

PMID- 11838994
TI  - Comparative evaluation of ultrasonography and lung function testing with the
      clinical signs and pathology of calves inoculated experimentally with Pasteurella
      multocida.
AB  - Seventeen calves were inoculated intratracheally with Pasteurella multocida 0 on
      three consecutive days with 10 ml of an inoculum containing 10(9) colony forming
      units/ml per day per calf. Before the first inoculation and 24 hours after the
      third, each calf was examined non-invasively by means of a clinical examination,
      chest ultrasonography, and impulse oscillometry to measure the impedance of the
      respiratory system. The inoculation of P multocida caused fever and a significant
      increase in respiratory rate and a decrease in tidal volume. There were also
      significant changes in the ultrasonographic results and in the impedance of the
      respiratory system. The percentage of the total surface area of the lungs showing
      pathological changes when the calves were euthanased 48 hours after the third
      inoculation ranged from 0.4 to 39 per cent. There were statistically significant
      correlations between the ultrasound scores and the pathological findings and
      between the ultrasound scores and the respiratory rate and tidal volume. The
      changes in the impedance of the respiratory system were not correlated with
      either the ultrasonographic or the pathological findings.

PMID- 11838995
TI  - Transmission of porcine reproductive and respiratory syndrome virus by needles.

PMID- 11838996
TI  - Reactivation of caprine herpesvirus 1 in experimentally infected goats.

PMID- 11838997
TI  - Pharmacy courses.

PMID- 11838998
TI  - Veterinary nurse training.

PMID- 11838999
TI  - Live haemorrhagic septicaemia vaccine for cattle and buffaloes.

PMID- 11839000
TI  - EC proposals on medicines.

PMID- 11839001
TI  - Cascade summing corrections for HPGe spectrometers by the Monte Carlo method.
AB  - Cascade summing corrections for application in HPGe gamma ray spectrometry have
      been calculated numerically by the Monte Carlo method. An algorithm has been
      developed which follows the path in the decay scheme from the starting state at
      the precursor radionuclide decay level, down to the ground state of the daughter
      radionuclide. With this procedure, it was possible to calculate the cascade
      summing correction for all gamma ray transitions present in the decay scheme.
      Since the cascade correction requires the values of peak and total detection
      efficiencies, another code has been developed in order to estimate these
      parameters for point and cylindrical sources. The radionuclides 60Co, 133Ba and
      131I were used for testing the procedure. The results were in good agreement with
      values in the literature.

PMID- 11839002
TI  - Determination of corrections to true summations of photons for measurements in
      Marinelli beakers.
AB  - This paper describes a method of determination of correction factors for the true
      summation effect of photons for measurement of activity of radionuclides emitting
      gamma radiation. The method was tested with Marinelli beakers samples measured
      with coaxial germanium detectors. The advantage of this method is its simplicity
      since it is not necessary to determine the curves of total efficiency for each
      detector. The correction factor for the particular peak is determined by means of
      a detector index which is calculated from one of the measurements with a
      calibration standard.

PMID- 11839004
TI  - Half-life measurements at the National Institute of Standards and Technology.
AB  - For nearly half a century the half-lives of many radionuclides have been measured
      with increasing precision. The results of these measurements for many long-lived
      radionuclides, such as 60Co, 137Cs, 85Kr, 133Ba, 207Bi, 152Eu, 154Eu, and 155Eu,
      have been updated recently by the Radioactivity Group of NIST. These long-lived
      radionuclides are used extensively to calibrate various nuclear counting and
      monitoring systems. The long-term precision of these calibrations can be greatly
      affected by the uncertainties in the calibrant half-lives. Results for the half
      lives of many radionuclides measured over the last four decades are tabulated. In
      addition, values of the half-lives of several short-lived radionuclides used in
      nuclear medicine are addressed, which are critical in determining the correct
      dosage given in patient treatment, are addressed. Comparisons with the
      recommended values from the International Atomic Energy Agency Coordinated
      Research Program and the Evaluated Nuclear Structure Data File from Brookhaven
      National Laboratory are presented and any apparent disagreements noted.

PMID- 11839003
TI  - A national campaign for coincidence-summing correction in gamma-ray spectrometry.
AB  - A national campaign was carried out in Italy for the application of coincidence
      summing correction in gamma-ray spectrometry. Twelve laboratories, belonging to
      the National Environmental Radioactivity Surveillance Network, took part in the
      campaign. They are equipped with gamma-ray spectrometry systems based on p- and n
      type HPGe detectors with different relative efficiencies. A simplified procedure
      was used for coincidence-summing correction. This procedure requires a single
      photon, single-nuclide source to measure the peak-to-total efficiency ratio at
      just one photon energy value. All the laboratories were given a 137Cs standard
      source for total efficiency determination, and a 134Cs source in the same
      geometry whose activity they had to determine. The results show the usefulness of
      the procedure. The average deviation of all the laboratory results from the ENEA
      INMRI reference value was reduced from -12% before correction to +1% after
      correction. The paper gives a description of the different organisational aspects
      of the campaign, reports the results obtained and draws conclusions in which the
      gain in measurement accuracy is evaluated in the light of the effort required for
      each participant to perform the correction.

PMID- 11839005
TI  - Determination of the emission probabilities of the principal gamma-rays for 134Cs
      to a high precision.
AB  - While multi-gamma-ray emitting nuclides such as 75Se, 134Cs and 152Eu have
      reasonably well-defined decay scheme, some inconsistencies still remain. Detailed
      evaluations and weighted-mean analyses result in the recommendation of gamma-ray
      emission probabilities with small uncertainties, although significant deviations
      exist in the measured values. Therefore, the gamma-ray emission probabilities of
      134Cs have been measured to a high precision after an extremely accurate
      calibration of detection efficiency. The resulting data agree extremely well with
      the evaluated values in IAEA-TECDOC-619 (IAEA, X-ray and gamma-ray standards for
      detector calibration, IAEA-TECDOC-619, IAEA, Vienna, 1991).

PMID- 11839006
TI  - Measurements of photon emission probabilities from the decay of 226Ra and
      daughters.
AB  - X- and gamma-rays spectrometric techniques have been used to determine and
      improve the photon emission probability data of 226Ra. These values were obtained
      from 226Ra spectra in radioactive equilibrium with daughters such as 222Rn, 214Bi
      and 214Pb in the 50-2500 keV energy range. The efficiency calibration of the
      coaxial and planar Ge detectors took into account correction factors for pile-up
      losses, attenuation and source geometry effects, and gamma-gamma and gamma-X
      summation losses. XK emission probabilities were successfully resolved and
      determined more precisely because of the ability to de-convolute complex regions
      of the spectrum below 90 keV combined with spectral knowledge of the interferring
      Pb-XK-rays. The resulting absolute intensities of the main photon emissions of
      226Ra and daughters exhibit improvements (+/-0.7% for the smallest uncertainty
      estimated to one standard deviation) or agree with published data.

PMID- 11839007
TI  - Determination of the beta- branching ratio of 64Cu by mass spectrometric
      investigations of the decay products in neutron transmuted copper.
AB  - The beta- branching ratio of 64Cu was determined by investigating the resulting
      decay products in copper doped by neutron transmutation. The numbers of 64Zn and
      64Ni atoms were analyzed using isotope dilution analysis combined with thermal
      ionization mass spectrometry. A beta- branching ratio of (38.06+/-0.30)% was
      obtained, which agrees with the study of Kawada (Appl. Radiat. Isot. 37 (1)
      (1986) 7) to a higher accuracy. However, our result differs from the value cited
      in the NUDAT database of (39.0+/-0.3)%.

PMID- 11839008
TI  - Efficiency curve of the ionization chamber of the SIR.
AB  - The efficiency of the SIR ionization chamber versus photon energy has been
      obtained by an iterative method, starting from a few monoenergetic gamma-ray
      emitters. The relative standard uncertainty on the efficiency curve obtained is
      lower than 10(-2) above 65 keV. An efficiency curve for beta particles has been
      deduced in a similar manner, from measurements of (quasi-) pure beta emitters.
      The possible uses of the efficiency curve to identify inconsistent SIR data or
      discrepant decay scheme data are discussed.

PMID- 11839009
TI  - Half-life determination of 40K by LSC.
AB  - The long-lived radioisotope 40K is one of the isotopes applied by geologists to
      date rocks hundreds or even thousands of millions of years old. Knowing the half
      life of 40K, the potassium-argon (K-Ar) method gives an estimate of the date of
      the rock's formation by measuring the quantity of the daughter stable isotope
      40Ar. As in the case of other radiometric methods, the results of the K-Ar dating
      method are generally accompanied by an error estimate, which includes the
      counting process, the uncertainty in the half-life of 40K and the beta to capture
      branching ratio. The objectives of this paper are basically three. First, we
      describe a procedure to incorporate the largest amount of the potassium cations
      into the liquid scintillator cocktail. This time, gels are able to provide much
      higher counting rates than the background. Second, Cerenkov counting gives the
      best shapefactor for 40K beta-ray transitions. Third, the CIEMAT/NIST method
      determines the activity of the samples and an averaged half-life for the
      radionuclide.

PMID- 11839010
TI  - Determination of precise gamma-ray emission probabilities for 88Rb.
AB  - Precise gamma-ray emission probabilities of 88Rb have been measured by 4pi beta
      gamma coincidence using a live-timed two-dimensional data-acquisition system. The
      absolute emission probabilities of the 898.1, 1836.1 and 2677.9 keV gamma rays
      were determined from the absolute gamma-ray intensities and the disintegration
      rates to be 14.68+/-0.13%, 22.73+/-0.15% and 2.123+/-0.021%, respectively. The
      relative intensities were measured for the weak gamma rays by a gamma-ray
      spectrometer, and the 88Rb decay scheme was determined from these results.

PMID- 11839011
TI  - Absolute determination of activity per mass and half-life measurements of 152Eu.
AB  - A solution of 152Eu was absolutely standardized by the 4pi beta (PPC)-gamma
      (HPGe) coincidence counting method as part of an intercomparison program
      coordinated by Bureau International des Poids et Mesures. The measured activity
      has been used to determine the calibration factor of the LNMRI reference
      ionization chamber for 152Eu. The half-life of 152Eu was also determined by means
      of a 4pi gamma ionization chamber to be (4963.6+/-15.3) days, and compared with
      others published values.

PMID- 11839012
TI  - Emission probabilities of the KX-rays following the decay of 237Np in equilibrium
      with 233Pa.
AB  - Following international EUROMET Project No. 416 and our recent measurement of the
      emission probabilities of the main gamma-rays of 237Np in equilibrium with 233Pa,
      a complementary work has been undertaken to determine the photon emission
      probabilities of the KX-rays associated with the decay of these nuclides. Two
      different analysis methods have been used: the KX-rays region was analyzed by
      fitting both Voigt and full response functions. Photon emission probabilities
      were determined with a relative uncertainty of about 2%.

PMID- 11839013
TI  - Evaluation of 169Yb decay data.
AB  - This evaluation of the complete decay scheme of 169Yb sums up the recent
      measurements carried out during an international exercise in which 11
      laboratories were involved, and also takes into account other independent
      experiments. As a result of the numerous high-quality measurements available, the
      decay scheme is shown to be highly consistent. The half-life is determined to be
      32.018 (5)d, and the emission probabilities of the two reference gamma lines of
      198 and 307 keV are recommended to be 35.93 (12)% and 10.046 (45)%, respectively.

PMID- 11839014
TI  - New features of the IC(4) code and comparison of internal conversion coefficient
      calculations.
AB  - The IC(4) software developed to compare calculated internal conversion
      coefficients (ICC) has been enhanced by adding new features through the use of
      Borland Delphi and TeeChart. Particularly, the 3D-graph option enhances the
      possibilities of analyzing calculated ICC values. For example, the comparison
      between the results given by three sets of theoretical ICC tables for any
      arbitrary pair of calculated ICC can be presented in a much clearer manner. Their
      differences can be displayed as energy vs. atomic number surfaces. Results from
      the analyses of K-shell and total ICCs for E2, E3, M2, M3, and M4 multipolarity
      are discussed.

PMID- 11839015
TI  - Self-absorption correction in standardisation of 204Tl.
AB  - In the frame of the CCRI(II) (Consultative Committee for Ionizing Radiation at
      the BIPM) working group on 204Tl, dedicated to investigate the problem and
      explain the reasons for the discrepancy between methods in standardisation of
      204Tl, IRMM was assigned the task of studying the influence of self-absorption in
      solid sources of 204Tl. This was investigated by measuring the activity of
      quantitative solid sources of different carrier content, prepared by employing a
      special source drying technique, developed at IRMM. The activity of the solid
      sources was determined using a 4pi pressurised proportional counter. The self
      absorption was calculated using the activity determined from liquid scintillation
      spectrometry, unaffected by self-absorption, as the reference value. After
      correction for foil absorption and non-detected X-rays, the self-absorption
      showed a linear relation to the logarithm of the dry mass of the source. For a
      typical source, the self-absorption correction for 204Tl was found to be as high
      as 8%. This article describes a way to minimise and correct for self-absorption
      in solid sources of 204Tl or nuclides with similar decay properties.

PMID- 11839016
TI  - Digital coincidence counting (DCC) and its use in the corrections for out-of
      channel gamma events in 4pi beta-gamma coincidence counting.
AB  - The digital coincidence counting system developed by NPL and ANSTO is briefly
      described along with its benefits in the data collection and processing for the
      4pi beta-gamma coincidence counting technique of radionuclide standardization.
      One of these benefits is the automatic detection of and correction for out-of
      channel coincidences in the Computer Discrimination method. Where the criteria
      for the use of the Cox-Isham/Smith correction formulae for dead times and
      resolving times are not met, a generalized approximation based on the work of
      Campion is suggested.

PMID- 11839017
TI  - A novel method for large-area sources preparation for the calibration of beta-
      and alpha-contamination monitors.
AB  - A method is proposed for the preparation of large-area reference sources for the
      calibration of beta- and alpha-contamination monitors. It is based on the
      incorporation, by the ion-exchange mechanism, of the radionuclide in a thin film
      of a conducting polymer ion-exchanger preliminarily grown on a metal support.
      Conducting pyrrole-based polymer functionalized by carboxylic cation-exchange
      groups is used to prepare 60Co and 90Sr-90Y beta-particle sources.
      Electrochemical polymerization of the corresponding monomer on different
      conducting supports is studied and a special electrochemical equipment developed
      permitting the preparation of large-area polymer films of controlled and
      reproducible thickness. The ion-exchanger obtained is characterized in terms of
      chemical affinity for cations Co2+ and Sr2+. Incorporation of the radionuclides
      in the large-area ion-exchanger films thus obtained is studied and optimized with
      respect to the uniform distribution of the radionuclide. The performance of the
      procedure is demonstrated using the example of circular sources 44 mm in diameter
      prepared on stainless steel supports. The sources obtained are characterized in
      terms of activity, beta-particle flux, uniformity and source efficiency.

PMID- 11839018
TI  - Standardization of 134Cs by three methods.
AB  - The nuclide 34Cs decays by beta-emission followed by gamma-deexcitation to 134Ba
      with a half-life T(1/2) = 2.065 a. It has been standardized by three methods:
      liquid scintillation counting (LSC), 4pi beta-gamma coincidence counting and 4pi
      gamma counting. In the LSC measurements, the CIEMAT/NIST method was used to
      calculate the efficiency. For the coincidence measurements, a conventional 4pi
      beta (proportional counter)-gamma(NaI) system was used. For the 4pi gamma
      standardization, a well-type Nal(Tl) detector was modeled with the Monte Carlo
      package PENELOPE, and the counting efficiency obtained by calculation. Results of
      the three methods agree within 0.65%.

PMID- 11839019
TI  - Production of Co-60 sources for high-accuracy efficiency calibrations of gamma
      ray spectrometers.
AB  - Activity determination by gamma-ray spectrometry is a valuable aid which is
      widely used where radioactive sources are applied. For the construction of an
      efficiency curve vs. energy in a standard geometry, the accuracy is limited not
      only by the uncertainty of peak area determination and the knowledge of the
      relevant emission probabilities but also by the uncertainties of the activity
      values applied to efficiency calibration with standard sources. Recently, a
      method to determine a relative efficiency function using selected radionuclides
      with gamma cascades of well known emission probabilities has been developed which
      yields very accurate efficiency values. Such a curve has to be converted into an
      absolute efficiency curve by calibration of the detector system with at least one
      source of very well known activity. Especially for this purpose, a set of Co-60
      gamma-ray spectrometer sources was produced at the PTB. The activity values (10
      45 kBq) were measured by the 4pi beta-gamma coincidence technique with a standard
      uncertainty of less than 0.1%. Production and measurement of these sources are
      described in the present paper. Special care was taken to include all
      contributions to the standard uncertainty of the activity value when establishing
      the uncertainty budget for the activity of each of these sources. The activity
      ratio of two of these sources, as obtained by the absolute measurements, was
      checked by independent gamma-ray counting at two other laboratories, where the
      precision achieved was less than 0.2%. The procedure described is considered to
      be a step towards more accurately determined efficiency functions in gamma-ray
      spectrometry.

PMID- 11839020
TI  - A dual-compensated cryogenic microcalorimeter for radioactivity standardizations.
AB  - Efforts are underway by our laboratory to develop a microcalorimeter that can be
      routinely used for radioactivity standardizations of nuclides that decay by pure
      beta-emission or by low-Z electron capture. The prototype calorimeter consists of
      a cryostat with two temperature-controlled stages and a base stage that are
      operated at nominal temperatures of 8 K. A unique aspect of the calorimeter's
      design is the ability to repeatedly engage and disengage the radioactive source
      from the second stage heat path using a magnetically activated elevator. The
      measurement of the total power from a radioactive sample is obtained from the
      difference in the second stage power with and without the source in place. As a
      result of extensive performance evaluations using 90Sr-90Y and 32P brachytherapy
      seeds as well as with an internal calibration heater, many initial design flaws
      have been identified and are being addressed.

PMID- 11839021
TI  - Analytical calculations of counting losses in internal gas proportional counting.
AB  - In internal gas proportional counting, the evaluation of counting losses is
      important in order to obtain high accuracy measurement results. In this paper,
      counting losses due to the wall effect and not counted beta particles with very
      low energy are evaluated by analytical calculations. The calculated and
      experimental results are compared and a very good agreement is found.

PMID- 11839022
TI  - Fitting methods for constructing energy-dependent efficiency curves and their
      application to ionization chamber measurements.
AB  - An ionization chamber without and with an iron liner (absorber) was calibrated by
      a set of radionuclide activity standards of the Physikalisch-Technische
      Bundesanstalt (PTB). The ionization chamber is used as a secondary standard
      measuring system for activity at the Slovak Institute of Metrology (SMU). Energy
      dependent photon-efficiency curves were established for the ionization chamber in
      defined measurement geometry without and with the liner, and radionuclide
      efficiencies were calculated. Programmed calculation with an analytical
      efficiency function and a nonlinear regression algorithm of Microsoft (MS) Excel
      for fitting was used. Efficiencies from bremsstrahlung of pure beta-particle
      emitters were calibrated achieving a 10% accuracy level. Such efficiency
      components are added to obtain the total radionuclide efficiency of photon
      emitters after beta decay. The method yields differences of experimental and
      calculated radionuclide efficiencies for most of the photon-emitting
      radionuclides in the order of a few percent.

PMID- 11839023
TI  - A new absolute method for the standardization of radionuclides emitting low
      energy radiation.
AB  - Microcalorimeters (or bolometers) operated at temperatures below 100 mK allow
      individual counting of photons and electrons with a very low energy detection
      threshold. The physics is based on the pulse temperature increase of the target
      (or absorber) of the detector due to the complete absorption of both electrons
      and photons. Since this target can be constructed with a perfect 4-pi geometry, a
      bolometer offers potentially a new method for absolute activity measurements of
      radionuclides emitting low-energy radiation. In this paper we present our first
      results of a feasibility study of activity standardization of a 55Fe solution
      with a prototype 4-pi bolometer.

PMID- 11839024
TI  - An improvement of uncertainty in activity standardization with efficiency tracer
      technique.
AB  - The activities of ten pure beta emitters were measured with two tracer nuclei for
      each one by using efficiency tracing technique. The determination results of
      specific activity of 35S, 63Ni and 185W, using efficiency tracers 60Co and 134Cs,
      are presented. The uncertainties of the final results for the three beta emitting
      nuclides were 0.5% at 99.7% confidence. The relationship between beta spectra and
      efficiency for the five nuclides were calculated with Fermi theory. The effects
      of the beta spectra shapes, end-point energies and chemical form of the tracers
      on the beta emitter activity results have been re-investigated. The type B
      uncertainty introduced by the upper limit of the fitting region (corresponding to
      the beta low detection efficiency), the polynomial fitting power (60Co as
      tracer), the lower limit of the fitting region (corresponding to self-absorption)
      and the gamma gate setting (134Cs as tracer) were investigated.

PMID- 11839025
TI  - The alpha and beta emitter measurement system in INER. Institute of Nuclear
      Energy Research.
AB  - An alpha/beta emitter measurement system used to calibrate surface sources
      following the guidelines of ISO 8769 has been established in Institute of Nuclear
      Energy Research (INER) around the year 2000. This system consists of a windowless
      proportional counter with a uniformity of 0.28% when measuring the emission rate
      of a source on a centered area of 100 mm x 150 mm, and a uniformity of 0.62% when
      the source area was 150 mm x 200 mm. Four 100 mm x 150 mm sources (90Sr + 90Y,
      36Cl, 14C and 241Am) had been measured by this system. The measurement results of
      the above four sources when compared with those of National Physical Laboratory,
      UK (NPL) showed difference between the two laboratories of < 1%.

PMID- 11839026
TI  - Software coincidence counting.
AB  - A system designed for absolute activity measurement is described using a digital
      method. The system is based on data recording from a coincidence measurement and
      subsequent software processing of the data records. The data acquisition device
      collects amplitudes of individual pulses from analogue-to-digital converters and
      supplies them with time information. Software processing of data records from
      this system offers many benefits in comparison to conventional coincidence
      counting, for example it enables to perform time and pulse height analysis and
      setting of coincidence parameters by using a wide variety of evaluation methods
      to one data record. The digital system was tested with a 4pi beta-gamma
      coincidence detectors arrangement consisting of a proportional counter and two
      NaI(Tl) scintillation detectors. The results obtained with a 60Co source are
      presented.

PMID- 11839027
TI  - A new set of electronic modules (NIM standard) for a coincidence system using the
      pulse mixing method.
AB  - The three electronic modules presented here, connected to two MTR2 modules of
      extended dead-time discriminators, allow setting-up a complete coincidence system
      according to the principle of the pulse-mixing method. Results produced by such a
      system including these modules were compared with those of an older system
      working in a completely different mode (IMPECC).

PMID- 11839028
TI  - Standardization of 152Eu and 88Y.
AB  - The activities of 152Eu and 88Y have been measured by the digital coincidence
      counting (DCC) technique and compared with those of the conventional coincidence
      counting technique. In the DCC, the pulse amplitudes from both beta and gamma
      channels are digitized in commercial ADCs and the pulse input times are
      simultaneously determined by 10 MHz oscillation clock installed in the
      coincidence module. The activity of the measured source is determined from the
      information of pulse height and input time for each pulse by off-line analysis.
      The activity of 152Eu was determined from extrapolations of efficiency functions
      obtained at 3gamma gates and the result showed a good agreement with that of the
      conventional method with 0.2% of uncertainty. The activity of 88Y was also
      determined by the DCC technique, and the reliability of the result was proved
      through Asia Pacific Metrology Program (APMP) inter-comparison of 88Y.

PMID- 11839029
TI  - Multi-method of standardization of radionuclides with "triangular scheme" of
      disintegration.
AB  - The new system of absolute methods of measurement of activity is presented in the
      paper. This system could be named a new generation of methods particularly for
      standardization of radionuclides with "triangular-scheme" of disintegration. The
      system is based on multi-parametric coincidence and anti-coincidence 4pi(LS)
      gamma methods. Theoretical considerations and experimental data of 51Cr-activity
      measurement using the above methods are presented. Finally, determination of the
      uncertainty for all the components in the multi-method system and the overall
      uncertainty for the system is presented.

PMID- 11839030
TI  - Study of the influence of the LS-cocktail composition for the standardisation of
      radionuclides using the TDCR model.
AB  - The influence of the LS-cocktail on the value of the ionisation quenching kB
      factor was investigated. Sets of 3H and 63Ni standard sources in some commercial
      and home-made scintillators of different compositions were prepared and measured
      using the TDCR method. The Birks kB factor was determined for each LS-cocktail
      and the results are discussed. A model of anisotropy of the triple counter caused
      by PM-tubes defocusing was applied for calculation.

PMID- 11839031
TI  - Determination of the 32P activity in angioplastic balloons by LSC.
AB  - The determination of the 32P activity in angioplastic balloons involves two
      problems: the extraction of 32P, which is covered with plastic foils, and the
      determination of the 33P impurity. At PTB the active balloons are destroyed by
      combustion in an oxygen stream. The active phosphorus is extracted quantitatively
      from the tube. The activities of 32P and 33P are determined by measurements
      performed over a period of one month or more by a subsequent data fit.

PMID- 11839032
TI  - The influence of stopping power on the ionisation quench factor.
AB  - Stopping power values for high energies have been computed applying the first
      Born approximation and the Bethe formula. However, this approximation tends to
      overestimate these cross sections at low energies, reaching discrepancies on the
      order of 50% at energies below 1 keV for most of the molecular targets of
      interest. In this paper we propose a method to obtain accurate low energy
      stopping powers of electrons by combining total cross section measurements with a
      theoretical treatment of the elastic process. We determine the optimum value of
      the kB parameter of ionisation quenching for the stopping power obtained in this
      paper.

PMID- 11839033
TI  - Development of MCTS technique for 3-PM liquid scintillation counting.
AB  - We have developed a multi-channel time scaling method that is suitable for
      activity measurement of beta emitting nuclides by means of 3-PM Liquid
      Scintillation Counting, using non-extending dead times and linear amplifiers.
      Since it enables to obtain the accidental coincidences directly, the true values
      for both double and triple coincidences are determined by simply taking into
      account the correction due to dead times. The advantages of the method are
      demonstrated by studying the activity of 204Tl and 14C. The measured results were
      compared with those derived by using the mathematical formulae.

PMID- 11839034
TI  - The standardization of 188W/188Re by 4pi beta liquid scintillation spectrometry
      with the CIEMAT/NIST 3H-standard efficiency tracing method.
AB  - The massic activity of a solution containing 188W in equilibrium with its
      daughter, 188Re, has been standardized by the National Institute of Standards and
      Technology using 4pi beta liquid scintillation counting with efficiency tracing
      using the CIEMAT NIST method. Confirmatory measurements were carried out with
      gamma-ray spectrometry using high purity germanium detectors and a 4pi gamma
      NaI(Tl) system. A calibration factor of 1.68 MBq pA(-1) +/-0.03 MBq pA(-1)
      (expanded, k = 2, uncertainty) for the 188W in the solution was determined, along
      with correction factors for activity determinations using Capintec dose
      calibrators. A half-life value of 69.78 d +/- 0.05 d (standard uncertainty) was
      determined by measurement in the NIST 4pi gamma ionization chamber and is
      consistent with currently recommended values.

PMID- 11839035
TI  - Calibration of the NPL secondary standard radionuclide calibrator for 125I seeds
      used for prostate brachytherapy. National Physical Laboratory.
AB  - In the therapeutic use of radionuclides, by far the most rapid growth in recent
      years is that of 125I seeds used for the treatment of prostate cancer. Large
      numbers of these seeds are used in each treatment and there is a need for a
      simple but accurate means of confirming their dose rates. This mechanism requires
      a transfer device for which the calibration factors are traceable to national
      standards. The NPL secondary standard radionuclide calibrator, because of its
      guaranteed reproducibility and traceable calibration procedure, is ideally suited
      for this purpose. A series of characterisation measurements have been performed
      on the NPL radionuclide calibrator in order to estimate the uncertainty levels
      that can be achieved and these are presented together with the relevant
      calibration factors for some typical seeds.

PMID- 11839036
TI  - Standardisation of 11C.
AB  - The increasing use of positron emission tomography for medical imaging and the
      availability of short-lived positron emitters has raised concerns about the
      accuracy of calibration of secondary standard measurement systems and the
      viability of using a single long-lived positron emitter as a reference
      calibration source for all positron emitters. Potential problems arise because
      the 511 keV quanta arising from positron annihilation are not generally produced
      at the same point as the original disintegration. In addition, the secondary
      standard may also be responsive to the associated bremsstrahlung radiation. The
      magnitude of both effects depends on the positron end-point energy. In order to
      resolve these problems, it is necessary to produce absolute standards of these
      positron-emitting radionuclides and the work presented here details the results
      of such work with 11C.

PMID- 11839037
TI  - Activity characterization of pure-beta-emitting brachytherapy sources.
AB  - A generalized approach for characterizing the activity content of sealed beta
      emitting sources has been developed, and was employed to establish National
      Institute of Standards and Technology based activity standardizations for three
      different types of intravascular brachytherapy sources. Initial ionization
      current measurements on the sources prior to destructive assays led to the
      establishment of calibration factors that can be used for subsequent non
      destructive measurements of similar sources. Activity characterizations are
      needed to unequivocally relate theoretic absorbed-dose modeling results to
      dosimetric measurements, as well as to establish production and quality controls
      by the source manufacturers, and to satisfy the requirements of various
      governmental regulatory authorities.

PMID- 11839038
TI  - The measurement of activity contained in a 32P stainless-steel stent by
      destructive assay.
AB  - Destructive assays of stainless-steel stents containing 32P were performed. Prior
      to assay, 24 stents were intercompared on a NaI(Tl) well-type crystal. A subset
      of stents were then digested in a suitable carrier solution by the addition of
      concentrated hydrofluoric acid. The final solution was measured by the
      CIEMAT/NIST tritium efficiency tracing method for liquid scintillation counting.
      A separate experiment was performed which indicated no loss of activity during
      stent digestion. Expanded (k = 2) uncertainties on stent activity ranged from
      1.0% to 2.6%.

PMID- 11839039
TI  - NPL secondary standard radionuclide calibrator. Syringe calibration factors for
      radionuclides used in nuclear medicine. National Physical Laboratory.
AB  - The measurement of the activity of a radiopharmaceutical administration to a
      patient is normally achieved via the use of a radionuclide calibrator. Although
      these radionuclides are normally measured initially in a standard glass vial, an
      aliquot of the solution is then usually withdrawn into a syringe prior to the
      administration. Both for general quality assurance good practice and for
      additional guarantees for patient safety, a confirmatory measurement of the
      syringe is almost obligatory Because of the different geometries and elemental
      compositions between plastic syringes and glass vials, the calibration factors
      for syringes may well be significantly different from those for the glass
      containers. The magnitude of these differences depends on the energies of the
      emitted photons. A variety of syringes typically used in hospital
      administrations, and covering a range of volumes and manufacturers, were
      obtained. The results obtained were compared to those for glass vials and show
      the large errors that can be produced by ignoring these differences in container
      format.

PMID- 11839040
TI  - Precise measurement of the activity of 186Re, 188Re radiopharmaceuticals.
AB  - The paper presents the results obtained in the assurance of traceability along
      the whole chain: production, distribution, use in hospitals, for the activity
      measurement of radiopharmaceuticals containing 186Re, 188Re and 186Re + 188Re
      mixtures. Standardization of the solutions, 4piPC-beta-efficiency relations and
      responses of a Centronic IG 12/20A ionization chamber and other radioisotope
      calibrators are presented. Gamma-ray and bremsstrahlung radiation contributions
      in the total response were evaluated. Some of the relevant results were compared
      with literature data.

PMID- 11839041
TI  - What can we expect from the CIEMAT/NIST method?
AB  - During the last years the CIEMAT/NIST (C/N) method was widely used to determine
      activities of different radionuclides. The impression is forced that the C/N
      method could be a universal method for all types of radionuclides. This paper
      shows under which conditions the C/N method can be used, where its limits are and
      which uncertainties can typically be achieved.

PMID- 11839042
TI  - Use of resonance ionization mass spectrometry for determination of Cs ratios in
      solid samples.
AB  - A method to quantitatively determine the radionuclidic content of complex samples
      with a minimum of chemical preparation has been under development at the National
      Institute of Standards and Technology (NIST). Based on earlier studies with
      resonance ionization mass spectrometry (RIMS), a graphite furnace was added to
      the RIMS system at NIST. Efficiency determinations for 133Cs in solution and
      isotopic ratio measurements of cesium (135Cs/137Cs) for an NIST nuclear burn-up
      sample using RIMS and for a sediment natural matrix standard using thermal
      ionization mass spectrometry are presented.

PMID- 11839043
TI  - A source for measurement of the absolute intensities of 226Ra gamma-radiation in
      equilibrium with decay products.
AB  - The design and production techniques of a gamma-ray spectrometric source of 226Ra
      in equilibrium with its daughter decay products have been developed. The radon
      emanation coefficient of the source did not exceed 0.1%. The 226Ra activity in
      the gamma-ray spectrometric source was measured relative to that in an alpha
      particle spectrometric source by comparison of the intensities of the main gamma
      rays using a semiconductor gamma-ray spectrometer. The total uncertainty of the
      activity measurement results was 0.5% for a coverage factor of k = 2.

PMID- 11839044
TI  - A ultra low level laboratory for nuclear test ban measurements.
AB  - The radionuclide laboratory at the Austrian Research Centers Seibersdorf (ATL03)
      was installed to support the international monitoring system for verification of
      the Comprehensive Nuclear-Test-Ban Treaty (CTBT and Text of the establishment of
      a Preparatory Commission for the Comprehensive Test-Ban-Treaty Organization,
      1996). Therefore, the background of a high-purity germanium detection system has
      been reduced by developing a high sophisticated active and passive detector
      shielding. The entire system is encapsulated in an iron-castle and placed into a
      fall-out shelter. The final count rate, achieved over the energy interval from 40
      to 2700 keV, amounts to 0.18 counts s(-1) kg(-1) (Ge).

PMID- 11839045
TI  - Comparison of methods for the analysis of 226Ra in water samples.
AB  - 226Ra is one of the key nuclides among the natural radionuclides from the point
      of view of radiation protection. For monitoring the radiation exposure risk along
      the water pathway it has to be measured routinely with low detection limits.
      Because of the properties of 226Ra and its progenies, a number of quite different
      methods are possible for this purpose. This paper presents a comparison of
      routine techniques for the determination of 226Ra in water samples as applied by
      the authors.

PMID- 11839046
TI  - Measurement of low levels of 26Al from meteorite samples.
AB  - As part of an intercomparison to resolve discrepancies between accelerator mass
      spectrometry results and radiometric results, the 26Al activity in four meteorite
      samples was measured using ultra low-level gamma-ray spectrometry in the
      underground laboratory HADES. Although reference sources were used, extensive use
      was made of computer modelling to determine corrections for absorption,
      coincidence summing between gamma rays in the decays and annihilation radiation
      following positron emission. Directional correlation corrections were also taken
      into account. The limiting uncertainties in these measurements arose from
      counting statistics of 5-9%. Some computer modelling was undertaken to determine
      optimum geometry for this type of intercomparison involving gamma-ray
      spectrometry.

PMID- 11839047
TI  - Deep underground gamma spectrometric measurement of 26Al in meteorite samples.
AB  - 26Al is routinely measured in meteorite samples by accelerator mass spectrometry
      (AMS). PTB participates in an international intercomparison between laboratories
      using AMS and gamma-ray spectrometry to improve the quality of such measurements.
      We performed gamma spectrometric measurements at the underground laboratory UDO
      using the GESPECOR software to calculate corrections for efficiency transfer,
      self-attenuation and coincidence summing. Four meteorite samples were measured
      for more than 30 days each but nevertheless, the uncertainty budgets are
      dominated by the uncertainties of the count rates.

PMID- 11839048
TI  - Radiochemical analysis of 93Zr.
AB  - The zirconium isotope 93Zr is a long-lived pure beta-particle-emitting
      radionuclide, which is produced by nuclear fission and neutron activation of the
      stable isotope 92Zr. This element is a constituent of the structural components
      of nuclear reactor vessels. A selective liquid-liquid extraction method for
      radiochemical separation of Zr, based on liquid-liquid extraction with 1-(2'
      thenoyl)-3,3,3-trifluoroacetone in xylene and a subsequent stripping of 93Zr by
      an aqueous acid solution, has been developed. The method was utilised to separate
      Zr from other pure beta-particle and beta-gamma emitters in different kinds of
      samples. Decontamination factors higher than 99% for the pure beta-particle and
      beta-gamma emitters and an overall chemical yield of 80% were obtained. The
      sensitivity of the method allows the determination of the isolated 93Zr by liquid
      scintillation counting and the minimum detectable activity value obtained was
      0.067 Bq over a counting period of 60 min.

PMID- 11839050
TI  - Results from APMP comparisons on radioactivity measurements of 58Co, 88Y and
      166mHo.
AB  - International comparisons on radioactivity measurements of 55Co, 88Y and 166mHo
      were carried out within the framework of the Asia-Pacific Metrology Programme.
      Radioactive sources were also sent to the International Reference System (SIR) at
      the Bureau International des Poids et Mesures (BIPM) in order to link the results
      of these regional comparisons to the BIPM key comparison-reference values. The
      arithmetic mean for the activity results of 166mHo was in good agreement with the
      SIR reference value, but some disagreements were found for 58Co and 88Y results.
      The mean values for 58Co and 88Y were both higher than the existing SIR values by
      about 1.5% and 0.9%, respectively. Although there were some disagreements, it was
      successfully demonstrated that these regional comparisons could be linked to
      other international key comparisons through the SIR. The present results were
      also evaluated to estimate a reasonable uncertainty level for each laboratory,
      which is very important in the establishment of an adequate traceability scheme
      for radioactivity standards.

PMID- 11839049
TI  - Standardization and decay data of 237Np.
AB  - This paper reports contributions from participants in the EUROMET project (No.
      416) which was entitled "237Np research into problems relating to purification,
      characterization and standardization". Primary standardizations were made by the
      defined low solid angle, coincidence, 4pi alpha, 2pi alpha and liquid
      scintillation counting methods. Secondary standardizations were made with
      calibrated gamma-ray spectrometers. Absolute X-ray, gamma-ray and alpha-particle
      emission probabilities were also determined. The results for the successful
      conclusion of both primary and secondary standardization are presented together
      with the values for alpha-particle and gamma-ray emission probabilities
      determined in this exercise. Several significant inconsistencies remain with the
      gamma-ray emission probabilities, and these are highlighted.

PMID- 11839051
TI  - The absolute counting of 166mHo, 58Co and 88Y.
AB  - In this study, absolute 4pi beta-gamma-coincidence counting was used to measure
      the mass activity of 166mHo, 58Co and 88Y. For 166mHo and 88Y, three gamma
      windows were set to study the systematic error caused by the different gamma
      window settings. To eliminate the effect arising from the large difference in
      counting efficiency of the 4pi beta counter between electron capture events and
      beta+ particles, the two-dimensional extrapolation method was used to measure
      58Co. The measurement results for the three nuclides were linked with the BIPM
      SIR through two APMP regional comparisons, APMP.RI(II)-K2, Ho-166m and
      APMP.RI(II)K2.Co-58, Y-88. Results are presented.

PMID- 11839052
TI  - Standardization of 152Eu.
AB  - 152Eu was standardized within the frame of a BIPM international comparison. The
      solution was prepared and bottled by PTB. The ampoules were measured at BIPM in
      the SIR ionization chambers and then dispatched to the participating
      laboratories. In the Radionuclide Metrology Laboratory of IFIN-HH, the solution
      was standardized using a coincidence method with "beta-efficiency extrapolation"
      by foil absorption. A simple 4pi beta-gamma-coincidence system was used, with
      NaI(Tl) and 4piPC detectors. No significant impurities were found apart for 0.5%
      154Eu. To obtain linear extrapolation plots, a "gamma-window" of 180-1500 keV was
      chosen. Dead-times of 10 micros were used. A combined uncertainty of 0.24% was
      obtained, mainly from the extrapolation procedure component.

PMID- 11839053
TI  - Disintegration rate measurement of a 152Eu solution.
AB  - The procedure followed by the Laboratorio de Metrologia Nuclear at the IPEN
      CNEN/SP, in Sao Paulo, for the standardization of 152Eu is described. The
      disintegration rate of 152Eu has been measured using the 4pi beta-gamma
      coincidence technique, using a 4pi proportional counter, filled with P-10 gas and
      operated at 0.1 MPa, coupled to one HPGe detector for the gamma-ray emission. Two
      discrimination windows were set in the gamma-channel, one related to the beta
      branch (344 keV) and the other related to the electron capture events (1408.03
      keV), in order to determine the counting efficiencies for beta, X-ray and Auger
      electron events in the proportional counter. The activity of solution was
      determined by a biparametric extrapolation curve obtained for the two selected
      gamma-windows.

PMID- 11839054
TI  - Standardisation of 89Sr using three different methods.
AB  - Three independent methods were used to standardise a 89Sr solution within the
      frame of an international comparison organised by BIPM/CCRI(II): 4pi liquid
      scintillation (LS) spectrometry, based on the CIEMAT/NIST efficiency tracing
      method, and direct activity measurements with a windowless 4pi CsI(Tl)-sandwich
      spectrometer and a 4pi pressurised gas proportional counter. Quantitative solid
      point-like sources were prepared paying special attention during the source
      drying phase. The impurities in the original solution were measured and corrected
      for in the results of all three methods. The activity concentration of 89Sr was
      found to be 26.21 +/- 0.08 kBq g(-1). A new half-life value for 89Sr of 50.61 +/-
      0.05 days was determined from the LS measurements. The measurement methods,
      including the impurity measurements, are described and the results compared.
      considering the advantages and disadvantages of each method.

PMID- 11839055
TI  - Standardization of 204Tl and 89Sr at VNIIM.
AB  - D.I. Mendeleyev Institute for Metrology (VNIIM) participated in two international
      comparisons of 204Tl and 89Sr solutions organized by the BIPM. The activity
      concentration was measured using the 4pi PC beta-counting method. Special
      attention was paid for investigating the dependence of the result on the inner
      diameter of the source support ring. For thin Al rings (100-200 microm), no
      dependence was detected. The beta-impurities in the 89Sr solution were determined
      using a scintillation plastic spectrometer. The combined standard uncertainty of
      the standardization of the 89Sr solution is 0.2%, and that for 204Tl is 0.4%.

PMID- 11839056
TI  - Standardization of 89Sr.
AB  - Two methods were used for the standardization of the pure beta-emitter 59Sr
      solution received in the framework of the 2000 BIPM comparison of activity
      measurements. The first method was by scintillation counting using the triple to
      double coincidence ratio (TDCR) technique. The existing three detector-system was
      improved by the inclusion of a MAC-3 module produced by LNHB-Saclay. This module
      contains the circuits for the coincidence, dead time and gate functions. This was
      the first use of this equipment in an international comparison. The DETECSZ
      program (LNHB) was used to obtain the activity concentration, at the reference
      time, as 26.09+/-0.21 kBq g(-1). The second method was the efficiency tracer
      technique, using a 60Co standard solution and a 4pi beta-gamma-coincidence
      system. The radioactivity concentration was calculated from a general
      extrapolation curve, by using data from several sources. The value was 26.58+/
      0.28 kBq g(-1) on the reference date 01.10.2000, 00 h UTC. The two results are in
      agreement within the limits of their combined uncertainties.

PMID- 11839057
TI  - Standardization of 89Sr at the National Office of Measures.
AB  - Strontium-89 is an important radiotherapy nuclide in bone palliation. The
      standardization of 59Sr has been performed at the National Office of Measures
      (OMH) within the frame of the BIPM CCRI(II)-K2.Sr-89 key comparison. The activity
      concentration of the 89Sr solution was measured by two different methods. The
      conventional 4pi beta counting technique was used with two proportional counting
      measurement systems. The 4pi beta-gamma-coincidence efficiency tracing method was
      used with a 4pi beta-gamma-coincidence measurement system using 24Na as the
      tracer radionuclide. The beta efficiencies of each of these counting techniques
      were nearly 100%. The combined uncertainties of the activity concentration
      determined by these absolute methods are 0.3%. The general agreement of results
      between the two methods was 0.5%. The measurement equipment, evaluation methods
      and results of activity concentration measurements with their uncertainty budgets
      are reported.

PMID- 11839058
TI  - Development of simulated-gas standards.
AB  - Multigamma simulated-gas standards were developed for monitoring the surrounding
      air at nuclear power plants by several commercial firms and laboratories. The
      main advantages of our simulated-gas standard consist of the easy preparation,
      gravimetrically spiking the matrix with a standardised multigamma radioactive
      solution. and that it does not require to be tested against actual gas standards.
      Self-attenuation correction factors for low gamma-ray energies were calculated.
      Original studies about the stability of the adherence of the dried radioactive
      residue to the matrix are presented and discussed.

PMID- 11839059
TI  - Standards of radium-226: from Marie Curie to the International Committee for
      Radionuclide Metrology.
AB  - In the early part of the 20th century, the pioneers of radioactivity research,
      led by Marie Curie, Ernest Rutherford and Stefan Meyer, formed a Commission
      internationale des etalons de radium. The Commission made arrangements for the
      preparation and intercomparisons of the international standards of radium, which
      were identified as the Paris standard and the Vienna standard. Otto Honigschmid
      from Vienna prepared a first set of international secondary standards in 1912 and
      a second set in 1934. In both instances, these secondary standards were compared
      by gamma-ray measurements with the Paris and Vienna standards. The usage of these
      international standards of radium in the 20th century is described.

PMID- 11839060
TI  - Precise efficiency calibration of an HPGe detector: source measurements and Monte
      Carlo calculations with sub-percent precision.
AB  - With the goal of measuring precise gamma-ray intensities for short-lived (< 5 s)
      accelerator-produced activities, we have calibrated the efficiency of an HPGe
      detector between 53 and 1836keV to sub-percent precision with a combination of
      source measurements and Monte Carlo calculations. Using known or independently
      measured detector dimensions, we have achieved both relative and absolute
      agreement (the latter, to 0.1%) between the calculated and measured efficiencies
      with only two adjustable detector parameters, the thicknesses of the contact dead
      layers.

PMID- 11839061
TI  - Transfer of the efficiency calibration of Germanium gamma-ray detectors using the
      GESPECOR software.
AB  - The GESPECOR software was extended to incorporate procedures for the computation
      of the efficiency transfer factor for cases of practical interest: (a) sources
      with identical geometry, but different matrices, (b) sources with similar (but
      not identical) geometry; and (c) transfer from a point source to a volume source.
      Fast and accurate algorithms. based on correlated sampling, were implemented for
      solving the first two cases. A procedure to take into account the imperfect
      charge collection in the detector was implemented.

PMID- 11839062
TI  - Measurement of the average path length of gamma-rays in samples using scattered
      radiation.
AB  - A method for measuring the average path length traversed by gamma-rays in a
      sample is presented. In this method the amount of radiation scattered within the
      sample at small angles and registered in the spectrum is measured. It is shown
      that the increase in counts in an energy interval close to the energy of the
      emitted gamma-rays, relative to the value attained in the absence of the
      interaction between the gamma-rays and the sample, is proportional to the average
      path length in the sample. Measurements of the average path length in samples of
      cylindrical geometry with various dimensions and at several energies are
      presented and compared with the predicted values. The differences between the
      measured and predicted values are discussed.

PMID- 11839063
TI  - Influence of nuclear data on uranium enrichment results obtained by XKalpha
      spectral region analysis.
AB  - During the recent international uranium exercise organized by the ESARDA NDA
      Working Group, several participants determined the uranium enrichment of samples
      using methods based on analysis of the XKalpha region of the uranium spectrum.
      For these methods, no calibration with known enrichment standards is required but
      accurate knowledge of nuclear data is needed. Despite this requirement, it
      appeared that during the exercise, four different sets of nuclear data were used
      by the participants. In view of this fact, it was decided to introduce these
      nuclear data sets into some computer codes in order to check their effects on the
      enrichment results. Two participants agreed to cooperate, and the main results of
      this test are presented here. It can be seen that three nuclear data sets,
      although different, give satisfactory results with no significant bias.
      Nevertheless, a more accurate characterization of X- and gamma-ray emission from
      235U, 235U and their daughters appears necessary.

PMID- 11839064
TI  - Characterization of three digital signal processor systems used in gamma ray
      spectrometry.
AB  - Various manufacturers have recently introduced digital signal processing systems
      that allow data acquisition in gamma spectrometry at high-input counting rates
      (several thousand pulses per second). In these systems, the signal digitization
      is performed immediately following the preamplification stage. This allows
      digital shaping and filtering of the signal which increases the number of
      possible combinations in signal shaping and as a consequence, optimizes the
      resolution as a function of the detector characteristics and the counting rate.
      Basic characteristic parameters of three digital signal processors that were
      recently introduced in the market have been studied and compared to those of an
      analog system. This study is carried out using a hyper-pure coaxial type
      germanium detector and 57Co, 60Co and 137Cs radioactive sources. Performance
      parameters such as energy resolution, system throughput, and counting losses that
      are due to dead time and pile-up effects are presented and discussed.

PMID- 11839065
TI  - Automated construction of detector models for efficiency interpolation in gamma
      ray spectrometry.
AB  - A method was developed for automated construction of detector models in gamma-ray
      spectrometry, which can be used in Monte Carlo calculations of efficiency
      calibration curves. Full-energy peak efficiencies were first measured for
      different gamma-ray energies and for a given sample-detector arrangement and then
      calculated by the Monte Carlo method. For these calculations a detector model was
      employed along with a computer algorithm, which seeks agreement between the
      experimental efficiencies and the calculated ones by automatically determining
      the parameters of the model. The resulting agreement of the calculated data with
      the experimental one was within the relative uncertainty of the latter (3-4%) and
      the parameters of the detector models obtained were close to the values specified
      by the manufacturers. The detector models thus constructed can then be used for
      interpolation of calibration curves.

PMID- 11839066
TI  - Determination of regional cerebral function with FDG-PET imaging in
      neuropsychiatric disorders.
AB  - Functional brain imaging using 18F fluorodeoxyglucose (FDG) and positron emission
      tomography (PET) has greatly enhanced our understanding of brain function both in
      normal conditions as well as in a wide variety of neuropsychiatric disorders. We
      review the uses of FDG PET in the diagnosis, management, and follow-up of
      patients with neuropsychiatric disorders. This article will also explore what FDG
      PET imaging has revealed in these neuropsychiatric disorders and how these
      findings relate to both research and clinical applications.

PMID- 11839067
TI  - Guest editorial: the conception of FDG-PET imaging.

PMID- 11839068
TI  - Whole-body FDG-PET imaging in the management of patients with cancer.
AB  - Fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging is increasingly
      used for the management of patients with cancer. The technique is now well
      accepted by most physicians as an effective complement to the existing imaging
      modalities. For many malignancies, PET achieves high sensitivity and specificity.
      The critical role of this powerful technique is realized increasingly in the day
      to-day practice of oncology. This is particularly true for the management of
      patients with non-small-cell lung cancer (NSCLC). The contribution of PET for the
      selection of patients eligible for curative treatments in this setting is well
      established. Convincing data also exist to support the use of PET for evaluating
      patients with recurrent colorectal carcinoma, for staging and restaging
      lymphomas, and for diagnosing recurrent thyroid carcinoma in the presence of
      elevated thyroglobulin and negative 131I scans. Other indications include staging
      of various recurrent malignancies, such as breast cancer, melanoma, and head and
      neck and gynecologic carcinomas. Existing data are limited for the determination
      of the impact of PET in certain malignancies, and further studies, which should
      include outcome information, will allow clarification of the role of this
      modality for such indications. Despite the small number of studies specifically
      designed to assess changes in management plans for some malignancies after
      performing PET the overall favorable results are encouraging enough at this time
      to include this modality as an essential element of the practice of modern
      oncology. Finally, the evolving role of PET imaging as a predictor of response
      after local or systemic treatment may add a major dimension to the application of
      this novel technique.

PMID- 11839069
TI  - 18-fluorodeoxyglucose positron emission tomographic imaging in the detection and
      monitoring of infection and inflammation.
AB  - During the past decade, 18-fluorodeoxyglucose (FDG) positron emission tomography
      (PET) has rapidly evolved from a pure research modality to a clinical necessity.
      FDG-PET was introduced to determine the state of brain function in physiologic
      and pathologic states. Its use as a powerful tool to diagnose, stage, and monitor
      patients with a variety of malignancies has been truly revolutionary. However,
      FDG is a nonspecific tracer and it has been found to accumulate at sites of
      infection and inflammation. It is becoming evident that PET imaging will play a
      major role in the treatement of patients with suspected infection and
      inflammation. PET has been shown to be particularly valuable in the evaluation of
      chronic osteomyelitis, infected prostheses, sarcoidosis, fever of unknown origin,
      and acquired immunodeficiency syndrome. Because of its ability to quantitate the
      rate of FDG uptake, PET may prove to be a powerful modality for the monitoring of
      disease activity and response to therapy. Novel PET tracers are being tested for
      imaging infection and inflammation that may further enhance the role of this
      technique in the appropriate clinical setting. PET imaging to detect and
      characterize infection and inflammation may become a major clinical indication in
      the day-to-day practice of medicine.

PMID- 11839070
TI  - Initial and subsequent approach for the synthesis of 18FDG.
AB  - 2-deoxy-2-[18F] fluoro-D-glucose (18FDG) was developed in 1976 in a collaboration
      between scientists at the National Institutes of Health, the University of
      Pennsylvania, and Brookhaven National Laboratory. It was developed for the
      specific purpose of mapping brain glucose metabolism in living humans, thereby
      serving as a tool in the basic human neurosciences. With 18FDG it was possible
      for the first time to measure regional glucose metabolism in the living human
      brain. Around the same time, the use of 18FDG for studies of myocardial
      metabolism and as a tracer for tumor metabolism were reported. After the first
      synthesis of 18FDG via an electrophilic fluorination with 18F gas (produced via
      the 20Ne(d,alpha)18F reaction), small volume enriched water targets were
      developed that made it possible to produce large quantities of [18F]fluoride ion
      via the high-yield 18(p,n)18F reaction. This was followed by a major milestone,
      the development of a nucleophilic fluorination method that produced 18FDG in very
      high yield. These advances and the remarkable properties of 18FDG have largely
      overcome the limitations of the 110-minute half-life of 18F so that 18FDG is now
      available to most regions of the United States from a number of central
      production sites. This avoids the need for an on-site cyclotron and chemistry
      laboratory and has opened up the use of 18FDG to institutions that have a
      positron emission tomography (PET) scanner (or other imaging device) but no
      cyclotron or chemistry infrastructure. Currently, 18FDG is used by many hospitals
      as an off the shelf radiopharmaceutical for clinical diagnosis in heart disease,
      seizure disorders, and oncology, the area of most rapid growth. However, it
      remains an important tool in human neuroscience and in drug research and
      development.

PMID- 11839071
TI  - 18F-deoxyglucose and the assessment of myocardial viability.
AB  - The glucose analogue 18F-deoxyglucose allowed for the first time the ability to
      noninvasively probe and characterize the regional metabolism of glucose as a
      major fuel substrate of the human heart. Used with positron emission tomography,
      it became the tool for demonstrating the operation of metabolic processes, long
      before established in invasive or destructive experiments in animals, directly in
      the human myocardium. Clinical investigations with 18F-deoxy-glucose, combined
      with other radiotracers of the myocardium's substrate metabolism, showed the
      dependency of the heart's substrate selection on circulating levels of glucose,
      free fatty acid and insulin, and the operation of Randle's cycle in the human
      myocardium. Regional responses in substrate metabolism to the myocardial ischemia
      were now visualized entirely noninvasively as, for example, decreases in fatty
      acid usage and oxidation and oxygen consumption, but foremost as an increase in
      glucose use. Regional 18F-deoxyglucose uptake markedly in excess of myocardial
      blood flow in dysfunctional myocardium of patients after a myocardial infarction,
      with chronic coronary artery disease or with ischemic cardiomyopathy, soon became
      recognized as a hallmark of myocardial viability or potentially reversible
      contractile dysfunction. Defined as blood flow metabolism mismatch, this
      particular regional glucose uptake pattern identifies patients to be at high risk
      for cardiac events and, at the same time, to benefit most from surgical
      revascularization. The patterns predict a postrevascularization improvement in
      global left ventricular function and, even more important, in symptoms related to
      congestive heart failure and in long-term survival. 18F-deoxyglucose is now
      widely used with positron emission tomography and, more recently, with single
      photon emission computed tomography and radiotracers of myocardial perfursion for
      stratifying ischemic cardiomyopathy patients to the most efficacious treatment.

PMID- 11839073
TI  - Children as co-researchers? Give them a chance.

PMID- 11839072
TI  - 18F FDG uptake in the large arteries: a correlation study with the atherogenic
      risk factors.
AB  - It has been reported that there is a high correlation between fluorodeoxyglucose
      (FDG) uptake in the aorta and macrophage content of atherosclerotic lesions in an
      experimental rabbit model. We evaluated the frequency of FDG uptake in the large
      arteries in relation to the atherogenic risk factors. We also investigated
      whether FDG uptake of the large arteries is related to clinically known coronary
      artery disease. The presence of FDG uptake was assessed in the abdominal aorta
      (AA), iliac (IA), and proximal femoral arteries (FAs) in 156 patients. Medical
      history of the atherogenic risk factors (age, cigarette smoking, hypertension,
      diabetes, high cholesterol, and obesity) and coronary artery disease (CAD) was
      identified for each patient. The frequency of vascular FDG uptake was compared
      between the patients without risk factors (Group I, 23 patients) and those with
      at least 1 risk factor (Group II, 133 patients). The correlation of each risk
      factor and known CAD with arterial FDG uptake was also assessed in the 3
      different arteries. There was a significant difference in the frequency of FDG
      uptake between the 2 groups for the FA (22% vs 70%) and IA (30% vs 54%), but not
      for the AA (35% vs 53%). Among all risk factors, age was the most significant and
      consistent factor correlating with FDG uptake in all 3 arteries.
      Hypercholesterolemia also correlated consistently with FDG uptake in all 3
      arteries. The correlation between the remaining risk factors and arterial FDG
      uptake was rather artery specific than consistent throughout all 3 arteries. A
      higher frequency of FDG uptake in the FA was seen in patients with CAD compared
      with those without CAD. Not all risk factors correlated with FDG uptake in
      different arteries. Among the risk factors, age and hypercholesterolemia most
      consistently correlated with FDG uptake in the AA, and the IA and proximal FAs.
      The positive correlation of arterial FDG uptake with the atherogenic risk factors
      suggested a promising role for FDG-PET imaging in the diagnosis of
      atherosclerosis and follow-up after treatment intervention.

PMID- 11839074
TI  - Monitoring service development through audit.
AB  - Comparative audits can be used as important tools for shaping service provision.
      Short stay facilities offer a more flexible and efficient approach to managing
      acute paediatric referrals. Users and providers views of the service are
      important. Children can be safely observed and discharged with parents empowered
      to continue care. Appropriate support systems should be in place in order to
      provide an ambulatory service.

PMID- 11839075
TI  - Teenage pregnancy: a reflective analysis.
AB  - Analysis of interview data from a television programme was undertaken in order to
      reflect upon a 16-year old girl's specific experience of pregnancy. Five major
      themes emerged from the thematic data content analysis 'role-modelling',
      'demographics', 'punishment', 'locus of control' and 'self-validation'. Analysis
      of the theme of 'role-modelling' suggests that constructions of childhood and
      concepts of health may be positively influenced by social learning. A client
      centred model of health promotion may aid health care workers when trying to
      promote the health of these young girls given the appropriate resources.

PMID- 11839076
TI  - 'A bridge to the future': impact on high dependency and intensive care.
AB  - The availability and increased demand on Paediatric Intensive Care beds continues
      on line with the advances with medical technology. The provision of District
      General Hospitals providing level 1 care and initiating level 2 is extremely
      important. Critically ill children requiring transfer to a tertiary centre
      require an efficient retrieval team. Care of critically ill children should
      always be provided by appropriate trained and experienced nursing staff. The
      partnership and negotiation of care for parents and relatives should be
      maintained as a high priority in PICU.

PMID- 11839077
TI  - Adherence to health advice amongst young people with chronic illness.
AB  - A literature review was undertaken to identify factors that may influence
      adherence to health advice amongst chronically ill young people. It emerged from
      the literature that internal and external factors influenced adherence in this
      client group. Internal influences were associated with adolescent biopsychosocial
      development and intra-personal dynamics. External factors were linked to
      interpersonal dynamics between the young person, family, peers, health care
      professionals and society as a whole. It is proposed that the difficulties in
      adherence to health advice were often due to 'adultist' beliefs. The implications
      of these findings are relevant to all health professionals involved in promoting
      health and in the development of approaches to promote 'young person-centred
      adherence.'

PMID- 11839078
TI  - Reflective growth and professional development: an ABC approach for the novice
      reflector.
AB  - This step guide acknowledges, today more than any other time in nursing history,
      nurses are being encouraged to evaluate and evidence learning. The UKCC
      guidelines on mandatory PREP (2001) demands a nursing profession who can evidence
      analysis of personal growth and development, learning from experience in
      practice. The step guide has been developed to enable novice reflectors to
      develop skills in reflective dialogue and writing. Nurses need guidance in this
      approach to learning more about themselves and the domain of nursing as for many
      it is a challenge to more formal modes of learning.

PMID- 11839080
TI  - Ethics in exercise science research.
AB  - Ethical evaluation is a vital but sometimes neglected component of research
      policy in the exercise sciences. This article reviews some issues in human
      research, with particular reference to studies undertaken by the exercise
      scientist. The typical composition and functions of the research review committee
      are examined in the context of individual and institutional ethical norms. In
      multicentre trials, there are often problems in coordinating ethical approval
      between institutions. On-going monitoring of research may have value in the
      detection of fraud. A reduction in the secrecy of committee proceedings would
      allow a closer auditing of the research review process. Authors need to give more
      thought to developing appropriate research questions. Scarce resources may be
      wasted because of inappropriate study design or an inadequate statistical
      analysis of the results. The costs of any proposed investigation must be weighed
      carefully against possible benefits. Confidentiality is particularly important
      when collecting data at the worksite or over the internet. Informed consent
      should be based on a full disclosure of risks; the participant should be
      competent to understand the nature and magnitude of these risks, and undue
      pressure to participate in an experiment must be avoided. The opposition to
      placebo trials expressed in the Declaration of Helsinki requires careful
      consideration of the use of control groups, since regular exercise is known to
      benefit health. If research is conducted in under-developed societies, the
      standards of treatment of the participants should match those expected in
      developed societies. The publication of findings must be fair and well balanced;
      examples of fraud and misconduct continue to be reported. Some journals
      apparently still publish papers, even if they have not received an initial
      institutional review. Editors should restore meaning to the word 'author', avoid
      the bias to a publication of 'positive' results, limit the impact of commercial
      sponsorship on reporting and curtail the current trend to redundant presentations
      and publications. Development of academic courses in research ethics may help to
      avoid some of these abuses.

PMID- 11839082
TI  - A pooled data analysis of injury incidence in rugby league football.
AB  - OBJECTIVE: The aim of this study was to summarise the injury rates in
      professional rugby league football. METHODS: Previously published studies were
      identified from database searches of the literature from Medline, Sports Discus
      and Web of Science. A total of 18 articles, which reported the prospective injury
      data collection for at least one playing season in professional rugby league
      worldwide, were included. The definition of injury adopted required an injured
      player to miss the subsequent game through injury. Ten studies satisfied the
      injury definition criteria for inclusion. A review of articles and extraction of
      relevant data were carried out independently by two authors. RESULTS: A total of
      517 injuries were reported during 12819 hours of exposure (753 games), which
      resulted in an overall injury rate of 40.3 injuries per 1000 hours [95%
      confidence interval (CI) 36.9 to 43.8]. Most injuries were to the lower half of
      the body (20.7 per 1000 hours, 95% CI 17.7 to 24), with the trunk receiving the
      least (6.7 per 1000 hours, 95% CI 5 to 8.6). CONCLUSIONS: Injury rates in
      professional rugby league are higher than in some other contact sports, probably
      because of the large number of physical collisions that take place. This pooled
      data analysis provides more accurate estimates of injury incidence in the game of
      professional rugby league football.

PMID- 11839079
TI  - Factors affecting levels of physical activity in adults.
AB  - A large proportion of adults in Western cultures are physically inactive, despite
      several decades of warnings about the potentially negative health consequences of
      a sedentary lifestyle. Efforts to promote physical activity have focused on
      identifying its determinants and designing interventions that might effectively
      promote regular physical activity. The multitude of factors that induce adults to
      initiate and maintain programmes of physical activity have been divided into
      those that are invariable (age, gender, race, ethnicity) and those that are
      presumed to be modifiable (behavioural and personality characteristics,
      environmental circumstances and community settings). The lack of consistency in
      the design, analysis and reporting of interventions in the lives of inactive or
      sedentary individuals has produced equivocal results. However, several social and
      environmental factors have systematically emerged as determinants of physical
      activity in adults. In ethnic minorities, the removal of barriers such as
      unaffordable facilities and unavailable childcare, high crime rates, fear for
      personal safety and culturally inappropriate activities are of primary
      importance. Social support from family, peers, communities and healthcare
      providers has resulted in modest improvements across cultures, ages and genders
      in selected settings, but the definition of specific interventions and their
      outcomes deserve additional attention. Longitudinal studies indicate that
      components of physical fitness are relatively transitory, with low to modest
      correlations between physical activity and measures of physical fitness in
      childhood and adolescence and in adulthood. Attempts to explain the activity
      behaviour of adults by applying various theories in programmes of intervention
      have also produced mixed results. Successful interventions tailor programmes to
      individual needs, account for personal levels of fitness, allow for personal
      control of the activity and its outcomes, and provide for social support by
      family, peers and communities. The initiation and maintenance of regular physical
      activity in adults depends on a multitude of biological and sociocultural
      variables that demand attention across the lifespan.

PMID- 11839083
TI  - Cross sections for low-energy (10-50 eV) electron damage to DNA.
AB  - We report direct measurements of the formation of single-, double- and multiple
      strand breaks in pure plasmid DNA as a function of exposure to 10-50 eV
      electrons. The effective cross sections to produce these different types of DNA
      strand breaks were determined and were found to range from approximately 10(-17)
      to 3 x 10(-15) cm(2). The total effective cross section and the effective range
      for destruction of supercoiled DNA extend from 3.4 to 4.4 x 10(-15) cm(2) and 12
      to 14 nm, respectively, over the range 10-50 eV. The variation of the effective
      cross sections with electron energy is discussed in terms of the electron's
      inelastic mean free path, penetration depth, and dissociation mechanisms,
      including resonant electron capture; the latter is found to dominate the
      effective cross sections for single- and double-strand breaks at 10 eV. The most
      striking observations are that (1) supercoiled DNA is approximately one order of
      magnitude more sensitive to the formation of double-strand breaks by low-energy
      electrons than is relaxed circular DNA, and (2) the dependence of the effective
      cross sections on the incident electron energy is unrelated to the corresponding
      ionization cross sections. This finding suggests that the traditional notion that
      radiobiological damage is related to the number of ionization events would not
      apply at very low energies.

PMID- 11839081
TI  - The unknown mechanism of the overtraining syndrome: clues from depression and
      psychoneuroimmunology.
AB  - When prolonged, excessive training stresses are applied concurrent with
      inadequate recovery, performance decrements and chronic maladaptations occur.
      Known as the overtraining syndrome (OTS), this complex condition afflicts a large
      percentage of athletes at least once during their careers. There is no objective
      biomarker for OTS and the underlying mechanism is unknown. However, it is not
      widely recognised that OTS and clinical depression [e.g. major depression (MD)]
      involve remarkably similar signs and symptoms, brain structures,
      neurotransmitters, endocrine pathways and immune responses. We propose that OTS
      and MD have similar aetiologies. Our examination of numerous shared
      characteristics offers insights into the mechanism of OTS and encourages testable
      experimental hypotheses. Novel recommendations are proposed for the treatment of
      overtrained athletes with antidepressant medications, and guidelines are provided
      for psychological counselling.

PMID- 11839084
TI  - Reductive damage in directly ionized DNA: saturation of the C5=C6 bond of
      cytosine in d(CGCG)(2) crystals.
AB  - Electron paramagnetic resonance (EPR) was used to study an oligodeoxynucleotide
      duplex of d(CGCG)(2) that is known to crystallize in Z-form. After X irradiation
      at 4 K, EPR data were collected on single crystals and polycrystalline samples as
      a function of annealing temperature and dose. A radical produced by the net gain
      of a hydrogen atom at C6 and a proton at N3, Cyt(C6+H, N3+H(+))(+*), is
      identified. This radical had not been positively identified in polymeric DNA
      previously. The Cyt(C6+H, N3+H(+))(+*) makes up about 4% of the total radical
      population at 4 K, increasing to about 10-15% after the DNA is annealed to 240 K.
      There appears to be neither an increase nor a decrease in the absolute
      concentration of Cyt(C6+H, N3+H(+))(+*) upon annealing from 4 K to 240 K.
      Additionally, the presence of another radical, one due to the net gain of
      hydrogen at C5 of cytosine, the Cyt(C5+H)(*), is implicated. Together, these two
      radicals appear to account for 60-80% of the reduced species in DNA that has been
      irradiated at 4 K and annealed to 240 K.

PMID- 11839085
TI  - Differential expression of cytokine genes in fibroblasts derived from skin
      biopsies of patients who developed minimal or severe normal tissue damage after
      radiotherapy.
AB  - Curative radiotherapy for cancer patients requires the use of radiation doses
      that are limited by the tolerance of the surrounding normal tissues.
      Unfortunately, these tolerance doses vary not only between tissues but also
      between individuals. In a small proportion of sensitive patients, exposure to
      radiation can lead to severe irreversible morbidity and even death several months
      to years after treatment. At present these radiosensitive patients can be
      identified only retrospectively. Here we describe a cytokine microarray technique
      that was used to identify differentially expressed gene transcripts in
      fibroblasts obtained from a small group of patients who suffered either
      negligible or severe normal damage to tissues after radiotherapy. If our
      preliminary findings can be confirmed, the availability of such markers may
      eventually allow the prediction of outcome prior to commencement of radiotherapy,
      and thus allow modification of radiotherapy protocols to minimize adverse late
      effects, without compromising tumor control.

PMID- 11839086
TI  - Promoter sequences involved in transforming growth factor beta1 gene induction in
      HaCaT keratinocytes after gamma irradiation.
AB  - Transforming growth factor beta 1 (TGFB1) is a cytokine involved in the
      development of both acute and late cutaneous radiation syndromes. We previously
      demonstrated that ionizing radiation induces TGFB1 expression in vivo in pig skin
      within a few hours. The purpose of the present study was to develop an in vitro
      human model to identify the mechanisms of this early activation. Accordingly,
      human HaCaT keratinocytes were irradiated with a single dose of 20 Gy. First,
      radiation-induced TGFB1 overexpression was checked at both the transcriptional
      and transductional levels in HaCaT cells. Then electrophoretic mobility shift
      assays (EMSA) and transient transfection with various TGFB1 promoter constructs
      were used to identify the sequences involved in regulating this promoter. EMSA
      analysis showed the induction of nuclear protein binding activity by gamma
      irradiation to the -365 AP1 sequence (TGTCTCA), suggesting the involvement of AP1
      sequences in the regulation of TGFB1 transcription. In gene reporter assays,
      maximal TGFB1 promoter activation was found for the longest construct, which
      contains two AP1 sequences. However, assays with constructs including deletions
      showed that these two AP1 sequences were not sufficient to confer TGFB1
      inducibility. These results showed for the first time, to our knowledge, that
      transcriptional regulation is involved in radiation-induced activation of TGFB1
      gene expression.

PMID- 11839087
TI  - Radiation-induced pulmonary fibrosis: examination of chemokine and chemokine
      receptor families.
AB  - Fibrosis is a common outcome of chronic inflammation or injury. Pulmonary
      fibrosis may be the result of abnormal repair after an acute inflammatory
      response. The process of repair initiated by a tissue insult is largely a
      function of the activation of cells to produce important biological mediators
      such as cytokines, growth factors and chemokines, which orchestrate most aspects
      of the inflammatory response. Consequently, altered regulation of the production
      of inflammatory cell cytokines and chemokines after injury and repair likely
      contributes to the fibrosis. Our hypothesis is that chronic expression of
      specific chemokine and chemokine receptors during the fibrotic phase induced by
      thoracic irradiation may perpetuate the recruitment and activation of lymphocytes
      and macrophages, which may contribute to the development of fibrosis. Fibrosis
      sensitive (C57BL/6) and fibrosis-resistant (C3H/HeJ) mice were irradiated with a
      single dose of 12.5 Gy to the thorax. Total lung RNA was prepared and hybridized
      using microarray analysis and RNase protection assays. At 26 weeks
      postirradiation, messages encoding the chemokines BLC (now known as Scyb13), C10
      (now known as Scya6), IP-10 (now known as Scyb10), MCP-1 (now known as Scya2),
      MCP-3 (now known as Scya7), MIP-1gamma (now known as Scya9), and RANTES (now
      known as Scya5) and the chemokine receptors Ccr1, Ccr2, Ccr5 and Ccr6 were
      elevated in fibrosis-sensitive (C57BL/6) mice. In contrast, only the messages
      encoding SDF-1alpha (now known as Sdf1) and Ccr1 were elevated 26 weeks
      postirradiation in fibrosis-resistant (C3H/HeJ) mice. Our results point to the CC
      and CCR family members as the predominant chemokine responders during the
      development of fibrosis. These studies suggest that monocyte/macrophage and
      lymphocyte recruitment and activation are key components of radiation-induced
      fibrosis.

PMID- 11839088
TI  - The recovery of the neurally evoked secretory response of rat colonic mucosa
      after irradiation is independent of mast cells.
AB  - The ability of the enteric submucosal plexus to influence the transport of water
      and electrolytes in the colon was investigated in rats for 1 week after acute
      whole-body gamma irradiation. The involvement of neuroimmune links in the
      epithelial responses to nerve stimulation was confirmed by the sensitivity of the
      tissue to tetrodotoxin, mepyramine and doxantrazole. At 1 and 3 days after
      irradiation, colon tissues were hyporesponsive to nerve stimulation. This was
      associated with a drastic diminution of mucosal mast cell numbers, tissue
      histamine levels, and rat mast cell protease II (RMCP II) levels, and by a
      decreased maximal epithelial response to exogenously added histamine. The
      responses to electric-field stimulation were insensitive to both mepyramine and
      doxantrazole. At 7 days, neurally evoked responses recovered, despite the virtual
      absence of mast cells, tissue histamine and RMCP II, and the continuing decreased
      response to histamine. The responses were insensitive to doxantrazole but were
      decreased by mepyramine. This study showed that the establishment of a normal
      epithelial response to neural stimulation can occur despite the radiation-induced
      depletion of mucosal mast cells. The recovery of the epithelial response, which
      was sensitive to mepyramine, may be ascribed to the reappearance of an unknown
      histaminergic pathway, which probably has indirect effects on epithelial
      transport but is independent of nerve-mast cell connections.

PMID- 11839089
TI  - Elevation of glutathione induced by low-dose gamma rays and its involvement in
      increased natural killer activity.
AB  - We examined the relationship between the induction of an increase in the level of
      glutathione and the elevation of natural killer (NK) activity in mouse
      splenocytes by a low dose of gamma rays. The glutathione levels in mouse
      splenocytes increased significantly between 2 h and 6 h after whole-body gamma
      irradiation at 0.5 Gy, peaked at 4 h, and then decreased almost to the level
      before irradiation by 12 h postirradiation. A significant enhancement of NK
      activity was found in the splenocytes obtained from whole-body-irradiated mice
      between 4 and 6 h postirradiation. Reduced glutathione (GSH) added exogenously to
      splenocytes obtained from normal mice enhanced both the total cellular
      glutathione content and the NK activity in a dose-dependent manner. Other
      precursors of de novo GSH synthesis, such as cysteine, N-acetylcysteine and
      oxidized glutathione, also increased the activity. These enhancements were
      completely blocked by buthionine sulfoximine, an inhibitor of de novo GSH
      synthesis. We conclude that the induction of endogenous glutathione in living
      cells immediately after low-dose gamma irradiation is at least partially
      responsible for the appearance of enhanced NK activity.

PMID- 11839090
TI  - Inflammatory and anti-inflammatory cytokines regulate the recovery from sublethal
      X irradiation in rat thymus.
AB  - We investigated the regeneration of rat thymus after sublethal X irradiation (6
      Gy). The number of thymocytes was much lower on day 3 after irradiation, and many
      apoptotic cells were observed. However, by day 5, there had been a rapid
      proliferation of thymocytes. Since cytokines are considered to be important
      regulatory factors in postirradiation recovery, we performed in vivo cytokine
      assays using semiquantitative reverse transcriptase-polymerase chain reaction (RT
      PCR) and found serial changes in the cytokine message. The messenger RNA (mRNA)
      expression of the pro-inflammatory cytokines interleukin 1 beta (Il1b), Il6 and
      tumor necrosis factor alpha (Tnf) was higher than normal on day 3, lower on day
      5, and higher again on day 7. In particular, Tnf was completely absent on day 5
      and was expressed again on day 7. Of the anti-inflammatory cytokines Il4,
      transforming growth factor beta (Tgfb) and Il10, only the Il10 message changed
      substantially. Il10 expression was very high on day 5 but was completely absent
      on day 7. Thus the Tnf and Il10 messages were expressed alternately. The changes
      in the distribution of macrophages detected by the immunohistochemical analysis
      may be related to the changes in the cytokines. Analysis of cytokine messages in
      the regenerating thymus in vivo may provide new insights into potential therapies
      for radiation-induced damage.

PMID- 11839091
TI  - Modulation of radiation-induced changes in the xanthine oxidoreductase system in
      the livers of mice by its inhibitors.
AB  - The xanthine oxidoreductase (XOD) system, which consists of xanthine
      dehydrogenase (XDH) and xanthine oxidase (XO), is one of the major sources of
      free radicals in biological systems. The XOD system is present predominantly in
      the normal tissues as XDH. In damaged tissues, XDH is converted into XO, the form
      that generates free radicals. Therefore, the XO form of the XOD system is
      expected to be found mainly in radiolytically damaged tissue. In this case, XO
      may catalyze the generation of free radicals and potentiate the effect of
      radiation. Inhibition of the XOD system is likely to attenuate the detrimental
      effects of ionizing radiation. We have examined this possibility using
      allopurinol and folic acid, which are known inhibitors of the XOD system. Swiss
      albino mice (7-8 weeks old) were given single doses of allopurinol and folic acid
      (12.5-50 mg/kg) intraperitoneally and irradiated with different doses of gamma
      radiation at a dose rate of 0.023 Gy/s. The XO and XDH activities as well as
      peroxidative damage and lactate dehydrogenase (LDH) were determined in the liver.
      An enhancement of the activity of XO and a simultaneous decrease in the activity
      of XDH were observed at doses above 3 Gy. The decrease in the ratio XDH/XO and
      the unchanged total activity (XDH + XO) suggested the conversion of XDH into XO.
      The enhanced activity of XO may potentiate radiation damage. The increased levels
      of peroxidative damage and the specific activity of LDH in the livers of
      irradiated mice supported this possibility. Allopurinol and folic acid inhibited
      the activities of XDH and XO, decreased their ratio (XDH/XO), and lowered the
      levels of peroxidative damage and the specific activity of LDH. These results
      suggested that allopurinol and folic acid have the ability to inhibit the
      radiation-induced changes in the activities of XDH and XO and to attenuate the
      detrimental effect of this conversion, as is evident from the diminished levels
      of peroxidative damage and the decreased activity of LDH.

PMID- 11839092
TI  - Sequence analysis of 193.4 and 83.9 kbp of mouse and chicken genomic DNAs
      containing the entire Prkdc (DNA-PKcs) gene.
AB  - The catalytic subunit of DNA-dependent protein kinase plays critical roles in
      nonhomologous end joining in repair of DNA double-strand breaks and V(D)J
      recombination. In addition to the SCID phenotype, it has been suggested that the
      molecule contributes to the polymorphic variations in radiosensitivity and
      susceptibility to cancer in mouse strains. Here we show the nucleotide sequence
      of approximately 193-kbp and 84-kbp genomic regions encoding the entire Prkdc
      gene (also known as DNA-PKcs) in the mouse and chicken, respectively. A large
      retroposon was found in intron 51 in the mouse but not in the human or chicken.
      Comparative analyses of the genome strongly suggested that the region contains
      only two genes for Prkdc and Mcm4; however, several conserved sequences and cis
      elements were also predicted.

PMID- 11839093
TI  - Resistance of 3'-phosphoglycolate DNA ends to digestion by mammalian DNase III.
AB  - An essential step in the repair of free radical-mediated DNA strand breaks is the
      removal of sugar fragments such as phosphoglycolate from the 3' termini. While
      the abasic endonuclease Ape1 can remove phosphoglycolate from single-strand
      breaks in double-stranded DNA, an enzyme capable of removing it from 3' overhangs
      of double-strand breaks has yet to be identified. We therefore tested DNase III,
      the predominant 3' --> 5' exonuclease in mammalian cell extracts, for possible 3'
      phosphoglycolate-removing activity. However, all 3'-phosphoglycolate substrates,
      as well as a 3'-phosphate substrate, were resistant to DNase III under conditions
      in which the analogous 3'-hydroxyl substrates were extensively degraded. The DNA
      end-binding protein Ku (an equimolar mixture of Ku70, now known as G22P1, and
      Ku86, now known as XRCC5) did not alter the resistance of the 3'-phosphoglycolate
      substrates, but the protein modulated the susceptibility of 3'-hydroxyl
      substrates, allowing DNase III to remove a 3' overhang but inhibiting digestion
      of the double-stranded portion of the substrate.

PMID- 11839094
TI  - Radiosensitivity of ataxia telangiectasia and Nijmegen breakage syndrome
      homozygotes and heterozygotes as determined by three-color FISH chromosome
      painting.
AB  - A three-color chromosome painting technique was used to examine the spontaneous
      and radiation-induced chromosomal damage in peripheral lymphocytes and
      lymphoblastoid cells from 11 patients with ataxia telangiectasia (AT) and from 14
      individuals heterozygous for an AT allele. In addition, cells from two homozygous
      and six obligate heterozygous carriers of mutations in the Nijmegen breakage
      syndrome gene (NBS) were investigated. The data were compared to those for
      chromosome damage in 10 unaffected control individuals and 48 cancer patients who
      had not yet received therapeutic treatment. Based on the well-documented
      radiation sensitivity of AT and NBS patients, it was of particular interest to
      determine whether the FISH painting technique used in these studies allowed the
      reliable detection of an increased sensitivity to in vitro irradiation of cells
      from heterozygous carriers. Peripheral blood lymphocytes and lymphoblastoid cells
      from both the homozygous AT and NBS patients showed the highest cytogenetic
      response, whereas the cells from control individuals had a low number of
      chromosomal aberrations. The response of cells from heterozygous carriers was
      intermediate and could be clearly differentiated from those of the other groups
      in double-coded studies. AT and NBS heterozygosity could be distinguished from
      other genotypes by the total number of breakpoints per cell and also by the
      number of the long-lived stable aberrations in both AT and NBS. Only AT
      heterozygosity could be distinguished by the fraction of unstable chromosome
      changes. The slightly but not significantly increased radiosensitivity that was
      found in cancer patients was apparently due to a higher trend toward
      rearrangements compared to the controls. Thus the three-color painting technique
      presented here proved to be well suited as a supplement to conventional
      cytogenetic techniques for the detection of heterozygous carriers of these
      diseases, and may be superior method.

PMID- 11839095
TI  - Wild-type TP53 inhibits G(2)-phase checkpoint abrogation and radiosensitization
      induced by PD0166285, a WEE1 kinase inhibitor.
AB  - The WEE1 protein kinase carries out the inhibitory phosphorylation of CDC2 on
      tyrosine 15 (Tyr15), which is required for activation of the G(2)-phase
      checkpoint in response to DNA damage. PD0166285 is a newly identified WEE1
      inhibitor and is a potential selective G(2)-phase checkpoint abrogator. To
      determine the role of TP53 in PD0166285-induced G(2)-phase checkpoint abrogation,
      human H1299 lung carcinoma cells expressing a temperature-sensitive TP53 were
      used. Upon exposure to gamma radiation, cells cultured under nonpermissive
      conditions (TP53 mutant conformation) underwent G(2)-phase arrest. However, under
      permissive conditions (TP53 wild-type conformation), PD0166285 greatly inhibited
      the accumulation of cells in G(2) phase. This abrogation was accompanied by a
      nearly complete blockage of Tyr15 phosphorylation of CDC2, an increased activity
      of CDC2 kinase, and an enhanced sensitivity to radiation. However, under
      permissive conditions (TP53 wild-type conformation), PD0166285 neither disrupted
      the G(2)-phase arrest nor increased cell death. The compound inhibited Tyr15
      phosphorylation only partially and did not activate CDC2 kinase activity. To
      understand the potential mechanism(s) by which TP53 inhibits PD0166285-induced
      G(2)-phase checkpoint abrogation, two TP53 target proteins, 14-3-3rho and CDKN1A
      (also known as p21), that are known to be involved in G(2)-phase checkpoint
      control in other cell models were examined. It was found that 14-3-3rho was not
      expressed in H1299 cells, and that although CDKN1A did associate with CDC2 to
      form a complex, the level of CDKN1A associated with CDC2 was not increased in
      response to radiation or to PD0166285. The level of cyclin B1, required for CDC2
      activity, was decreased in the presence of functional TP53. Thus inhibition of
      PD0166285-induced G(2)-phase checkpoint abrogation by TP53 was achieved at least
      in part through partial blockage of CDC2 dephosphorylation of Tyr15 and
      inhibition of cyclin B1 expression.

PMID- 11839096
TI  - Spectrum of Znfn1a1 (Ikaros) inactivation and its association with loss of
      heterozygosity in radiogenic T-cell lymphomas in susceptible B6C3F1 mice.
AB  - Ikaros (now known as Znfn1a1), a Kruppel-type zinc-finger transcription factor
      that plays a critical role in both lineage commitment and differentiation of
      lymphoid cells, has recently been shown to function as a tumor suppressor gene.
      We have previously reported a high frequency of LOH (approximately 50%) at the
      Znfn1a1 locus in radiation-induced T-cell lymphoma in susceptible B6C3F1 mice.
      The aim of the present study was to delineate the types of Znfn1a1 inactivation,
      with special reference to the LOH status, and to determine the relative
      contribution of each type of Znfn1a1 inactivation in radiation-induced T-cell
      lymphomas in B6C3F1 mice. We demonstrated that Znfn1a1 was frequently altered (in
      approximately 50% of T-cell lymphomas), and that its inactivation was caused by a
      variety of mechanisms, which came under one of the following four categories: (1)
      null expression (14%); (2) expression of unusual dominant-negative isoforms
      (11%); (3) amino acid substitutions in the N-terminal zinc-finger domain for DNA
      binding caused by point mutations (22%); (4) lack of the Znfn1a1 isoform 1 due to
      the creation of a stop codon by insertion of a dinucleotide in exon 3 (3%). The
      null expression, amino acid substitutions, and dinucleotide insertion
      inactivation types were well correlated with LOH at the Znfn1a1 allele (86%) and
      were consistent with Knudson's two-hit theory. On the other hand, T-cell
      lymphomas expressing dominant-negative Znfn1a1 isoforms retained both alleles.
      These results indicate that Znfn1a1 inactivation takes place by a variety of
      mechanisms in radiation-induced murine T-cell lymphomas and is frequently
      associated with LOH, this association depending on the type of inactivation.

PMID- 11839097
TI  - Mapping the distribution of (90)Sr in teeth with a photostimulable phosphor
      imaging detector.
AB  - The present communication describes the technical aspects of the first
      application of an imaging plate for visualization of (90)Sr deposited in human
      teeth. The teeth were obtained from Techa River area residents who were exposed
      as a result of releases of radioactivity into the Techa River by the first Soviet
      nuclear plant Mayak in the early 1950s. The investigations form the basis for an
      experimental procedure for accurate mapping of the distribution of (90)Sr in
      teeth with an imaging plate. This new method can be used as an individual
      indicator of radionuclide intake. Its advantages are its high sensitivity (0.02
      Bq/g mm(-2) of (90)Sr), it ability to examine small detectable cross-sectional
      areas of dental tissue (dentin) contaminated with (90)Sr (from 0.01 mm(2)), the
      nondestructive method of analysis, and the simplicity of use. The combined
      application of this method with EPR tooth biodosimetry can provide more accurate
      dose reconstruction and may lead to more effective radiation risk assessment.

PMID- 11839099
TI  - Featural vs. configurational information in faces: a conceptual and empirical
      analysis.
AB  - The perception and memory of faces have been accounted for by the processing of
      two kinds of facial information: featural and configurational. The starting point
      of this article is the definition and accepted usage of these two concepts of
      facial information. I discuss these definitions and their various ramifications
      from three aspects: methodological, theoretical and empirical. In the section on
      methodology, I review several of the basic manipulations for changing facial
      information. In the theoretical section, I consider four fundamental hypotheses
      associated with these two kinds of facial information: the featural,
      configurational, holistic and norm hypotheses (the norm-based hypothesis and the
      'hierarchy of schemas' hypothesis). In the section on empirical evidence, I
      survey relevant studies on the topic and consider these hypotheses through a
      description of various empirical phenomena that carry clear implications for the
      subject of the study. In conclusion, I propose two alternative directions for
      future research: first, a 'task-information' approach, which involves specifying
      what information is used for different tasks; and secondly, taking a different
      approach to the definition of the visual features for face processing, for
      example by using principal components analysis (PCA).

PMID- 11839098
TI  - The response of a spherical tissue-equivalent proportional counter to iron
      particles from 200-1000 MeV/nucleon.
AB  - The radiation environment on board the space shuttle and the International Space
      Station includes high-Z and high-energy (HZE) particles that are part of the
      galactic cosmic radiation (GCR) spectrum. Iron-56 particles are considered to be
      one of the most biologically important parts of the GCR spectrum. Tissue
      equivalent proportional counters (TEPCs) are used as active dosimeters on manned
      space flights. These TEPCs are further used to determine the average quality
      factor for each space mission. A TEPC simulating a 1-microm-diameter sphere of
      tissue was exposed as part of a particle spectrometer to (56)Fe particles at
      energies from 200-1000 MeV/nucleon. The response of TEPCs in terms of mean lineal
      energy, y(F), and dose mean lineal energy, y(D), as well as the energy deposited
      at different impact parameters through the detector was determined for six
      different incident energies of (56)Fe particles in this energy range.
      Calculations determined that charged-particle equilibrium was achieved for each
      of the six experiments. Energy depositions at different impact parameters were
      calculated using a radial dose distribution model, and the results were compared
      to experimental data.

PMID- 11839100
TI  - Implicit and explicit processes in a hypothesis testing task.
AB  - We present the results of two experiments investigating the factors that
      determine responding on the pseudo-diagnosticity task. In Expt 1 we manipulated
      people's beliefs about the degree to which an initial piece of evidence supported
      a focal hypothesis and found decreased pseudo-diagnostic (PD) responding when the
      evidence offered low support for the focal hypothesis. In Expt 2 we manipulated
      the instructions given to participants. We found that instructions to select
      evidence to help decide between the focal and the complementary hypotheses
      produced fewer PD responses than both instructions to decide whether the focal
      hypothesis was the case and instructions to decide whether its complement was the
      case. The results are interpreted within the framework of recent dual process
      theories of reasoning.

PMID- 11839101
TI  - Negative priming from the non-selected meaning of the homograph.
AB  - In this article we address the question of whether semantic ambiguity resolution
      involves the central inhibition of the non-selected meaning of a homograph. Most
      previous studies on this topic have either not clearly required semantic
      selection, or have induced this disambiguation by manipulating the context. These
      studies have not observed clear inhibitory effects on the non-selected meaning of
      the type studied in negative priming. We suggest that this kind of central
      inhibition may depend on task demands, and will be more easily observed in tasks
      where meaning selection is clearly required and is not made easier by cueing or
      context. In this study, participants had to perform a semantic judgment task in
      the prime display. Semantic priming from both the selected and the non-selected
      meaning of homographs was measured by showing facilitation for the selected
      meaning and inhibitory effects of the non-selected meaning. Participants with
      slow but accurate performance during the task were mainly responsible for this
      semantic negative priming effect, reflecting the role of inhibition on task
      oriented control. The 'negative priming' effect is discussed in relation to
      current theories of attentional selection.

PMID- 11839102
TI  - Conceptualization and measurement of celebrity worship.
AB  - Celebrity worship has been conceptualized as having pathological and
      nonpathological forms. To avoid problems associated with item-level factor
      analysis, 'top-down purification' was used to test the validity of this
      conceptualization. The respondents (N = 249) completed items modelled after
      existing celebrity worship questionnaires. A subset of 17 unidimensional and
      Rasch scalable items was discovered (the local reliability ranged from.71 to.96),
      which showed no biases related to age and gender. This subset was dubbed the
      Celebrity Worship Scale (CWS). The items also showed no celebrity bias,
      indicating that CWS applies equally to acting, music, sports, and 'other'
      celebrities. The Rasch nature of the items defines celebrity worship as
      consisting of three qualitatively different stages. Low worship involves
      individualistic behaviours such as watching and reading about a celebrity. At
      slightly higher levels, celebrity worship takes on a social character. Lastly,
      the highest levels are characterized by a mixture of empathy with the celebrity's
      successes and failures, over-identification with the celebrity, compulsive
      behaviours, as well as obsession with details of the celebrity's life. Based on
      these findings, the authors propose a model of celebrity worship based on
      psychological absorption (leading to delusions of actual relationships with
      celebrities) and addiction (fostering the need for progressively stronger
      involvement to feel connected with the celebrity).

PMID- 11839103
TI  - The determinants of spoken and written picture naming latencies.
AB  - The influence of nine variables on the latencies to write down or to speak aloud
      the names of pictures taken from Snodgrass and Vanderwart (1980) was investigated
      in French adults. The major determinants of both written and spoken picture
      naming latencies were image variability, image agreement and age of acquisition.
      To a lesser extent, name agreement was also found to have an impact in both
      production modes. The implications of the findings for theoretical views of both
      spoken and written picture naming are discussed.

PMID- 11839104
TI  - Visual search within and across dimensions: a case for within-dimension grouping.
AB  - We used a visual search task in which participants searched for the presence of
      either both members or just one member of pairs of spatially separated simple
      visual features. Pairs of target features could be drawn either from within the
      same dimension (two colours, or two orientations) or from across two different
      dimensions (one colour and one orientation). In Experiment 1, display items
      carrying target and non-target features (target and distractor items
      respectively) were presented at interspersed spatial locations. Reaction times
      (RTs) to find both of two feature targets were generally slower than to find one
      feature target for within- and across-dimension target pairs alike. This slowing
      was approximately constant across display set sizes, with one exception: for
      within-dimension targets, two features could be detected as fast as single
      features when there were just two items in displays. Experiment 2 replicated the
      finding across all display set sizes when target items were always spatially
      adjacent rather than interspersed with distractor items. We interpret these data
      in terms of grouping between target features within the same dimension, and argue
      against there being any qualitative limit on visual processing or selection when
      target features come from a single dimension relative to when they come from
      separate dimensions.

PMID- 11839105
TI  - An analogue study of attributional complexity, theory of mind deficits and
      paranoia.
AB  - Recent research suggests that the tendency of paranoid individuals to attribute
      negative events to external personal factors and positive events to internal
      factors may be associated with difficulties in understanding the mental states of
      others, referred to as theory of mind (ToM). The present study aimed to
      investigate the relationship of these factors with attributional complexity and
      motivation. In an analogue sample, a relative ToM impairment was associated with
      an increased tendency to attribute negative events to external personal factors
      but not with differences in attributional complexity. This indicates that
      paranoid tendencies and mentalizing deficits are not associated with
      attributional simplicity, but may be related to schematic patterns of cognition.

PMID- 11839106
TI  - Anger and it's management for survivors of acquired brain injury.
AB  - Uncontrollable anger is a common problem for people with acquired brain injury
      (ABI). Little is known about how to properly manage this kind of anger, since it
      can result from both neuropsychological and psychological factors associated with
      the brain damage. Moreover, the outcome research on anger treatments is lacking.
      This paper is an examination of the causes of anger problems in this population,
      as well as a review of the basic therapeutic techniques typically used to treat
      anger with suggested alterations for their implementation with people with ABI.
      This literature will be integrated into a model that can be useful for helping
      people with ABI to handle their anger in an appropriate fashion. Finally, this
      paper will discuss the advantages of conducting anger management in a group
      format for people with ABI.

PMID- 11839107
TI  - Glycogen-rich and glycogen-depleted astrocytes in the oedematous human cerebral
      cortex associated with brain trauma, tumours and congenital malformations: an
      electron microscopy study.
AB  - PRIMARY OBJECTIVE: The anaerobic mobilization of astrocyte glycogen in anoxic
      ischemic regions of the oedematous human cerebral cortex is analysed. METHODS AND
      PROCEDURES: Seventeen cortical biopsies of patients with brain trauma, brain
      tumours and congenital malformations were examined by conventional transmission
      electron microscopy. RESULTS: Glycogen-rich and glycogen-depleted, clear or dense
      astrocytes cell bodies were observed in anoxic ischaemic regions of different
      brain cortical areas in perineuronal, neuropilar and perivascular localization.
      Glycogen-rich astrocytes showed clear or moderately dense cytoplasm and
      accumulation of both beta-type or monogranular glycogen granules and alpha-type
      or multigranular glycogen particles. Focal regions of translucent cytoplasm were
      observed in areas of glycogen degradation. Glycogen-depleted astrocytes exhibited
      a clear cytoplasm and scarce amount or absence of beta-type glycogen granules.
      Coexisting glycogen-rich and glycogen-depleted neuropilar astrocytic processes
      were observed in the vicinity of degenerated myelinated axons and degenerated
      axodendritic contacts. Glycogen-rich and glycogen-depleted perivascular
      astrocytic processes were also found surrounding injured and collapsed cerebral
      capillaries. CONCLUSION: The findings suggest astrocytic glycogen mobilization
      during anoxic and ischaemic conditions, revealing the important contribution of
      astrocytes on neuronal survival under conditions of energy substrate limitations.

PMID- 11839108
TI  - Evaluating money management skills following brain injury using the assessment of
      functional monetary skills.
AB  - Using money, totalling currencies, paying bills, writing cheques, or making
      purchases are daily occurrences. The various cognitive sequelae of brain injury
      (e.g. attention, language, executive functions) often disrupt an individual's
      money management skills. This paper describes the development and characteristics
      of a new instrument, the Assessment of Functional Monetary Skills (AFMS),
      designed to evaluate practical and functional money management skills in
      individuals with brain injury. The advantages of the AFMS compared to other
      similar instruments are also discussed. In addition, three case illustrations of
      individuals with brain injury are provided which describe both the quantitative
      and qualitative information that result from administrating the AFMS, and how
      such information is valuable in rehabilitating money management skills.

PMID- 11839109
TI  - Classifying mobility recovery in children and youth with brain injury during
      hospital-based rehabilitation.
AB  - PRIMARY OBJECTIVE: This article describes mobility recovery for children and
      youth with traumatic and non-traumatic brain injury during hospital-based
      rehabilitation. RESEARCH DESIGN: A retrospective, descriptive pre-test/post-test
      design was used. METHODS AND PROCEDURES: One hundred and fifty-seven individuals
      with brain injury who were admitted for rehabilitation over a 5-year period were
      enrolled in this study. The Paediatric Evaluation of Disability Inventory (PEDI)
      was used to document functional mobility at admission and discharge from the
      rehabilitation programme. The PEDI mobility classification system consisting of
      seven discrete levels of mobility was developed to provide clinically relevant
      and succinct outcome information. MAIN OUTCOMES AND RESULTS: The majority of
      children with brain injury (69%) improved one or more mobility classification
      levels. Children in the traumatic brain injury group made greater changes (p =
      0.001) in mobility recovery than children in the non-traumatic group.
      CONCLUSIONS: Information about recovery using a well-defined functional
      classification system may assist with programme evaluation and facilitate optimal
      service delivery.

PMID- 11839110
TI  - Quantitative assessment of impairment in constructional ability by cube copying
      in patients with aphasia.
AB  - Constructional apraxia was evaluated in patients with aphasia using a cube
      copying task. It was assessed whether quantitative assessment of cube copying
      could be used to estimate the performance intelligence quotient (IQ) according to
      neuropsychological tests. Abnormality in the cube-copying test was observed in 42
      of 46 patients (91.3%). Performance according to Raven's coloured progressive
      matrices and the revised Wechshler adult intelligence scale (WAIS-R) in patients
      with poor cube copying was significantly lower than in the other four patients.
      Numbers of the connections completed and plane-orientation errors made in the
      cube-copying test were significantly correlated with performance IQ on the WAIS
      R, correlating particularly with block design, digit symbol, and object assembly
      in performance IQ subtests. The quantitatively scored cube-copying test, then,
      can roughly predict non-verbal IQ in patients with aphasia.

PMID- 11839111
TI  - Critical review of passive muscle stretch: implications for the treatment of
      children in vegetative and minimally conscious states.
AB  - The efficacy of passive muscle stretch in the treatment of children in vegetative
      (VS) and minimally conscious (MCS) states is reviewed. Seventeen studies are
      critically reviewed. Study quality was evaluated using a quality filter adapted
      from Guyatt. Levels of evidence were assigned to each study using criteria based
      on Sackett's guidelines and a recent adaptation of those guidelines. Based on
      these levels of evidence, specific recommendations were made. These
      recommendations were classified as grade A, B, C or D depending on the levels of
      evidence used to generate them. There is limited evidence to support the efficacy
      of passive muscle stretch to improve range of motion and reduce spasticity in
      children in VS and MCS. Caution must be used when interpreting these
      recommendations because of the limited number of studies available and the
      extrapolation of study results from a different population. Further research is
      needed to strengthen these recommendations and establish the efficacy of passive
      muscle stretch in the treatment of children in VS and MCS.

PMID- 11839112
TI  - The WHO Quality of Life (WHOQOL) Questionnaire: Danish validation study.
AB  - The objective of this pilot study was to evaluate the Danish translation of the
      WHO Quality of Life Questionnaire, the WHOQOL, by means of the psychometric
      properties of the Danish version. The translation method followed the WHO
      standard procedures, including forward and backward translation, focus group
      discussions, and assessment of response choice weighting through visual analogue
      scales. In the study we evaluated the applicability of the WHOQOL in patients
      with physical and mental disorders compared with a sample of healthy controls.
      The WHOQOL was compared with health-related quality of life questionnaire SF36
      (Short Form 36). The internal consistency or homogeneity of the Danish WHOQOL was
      found adequate, and its applicability and its performance in distinguishing
      between population groups were satisfactory. The abbreviated version of WHOQOL
      100, the WHOQOL-BREF, was analysed separately and was also found psychometrically
      valid. The WHOQOL is a questionnaire that is easy to administer, and it seems
      applicable for use.

PMID- 11839113
TI  - Predictors of delayed social maturation and mental health disorders in young
      adults chronically ill since childhood.
AB  - To ascertain the influence of juvenile-onset chronic physical diseases and
      associating factors of social environment on delayed social maturation and mental
      health disorders in young adults, we analysed a group of 407 (184 female, 223
      male) subjects with these conditions and compared the results with those of 123
      (63 female, 60 male) healthy controls studied at the age of 19-25 years. The
      social maturation index was formed on the basis of a demographic interview, which
      also reviewed the state of social development and the family situation during
      childhood. Mental health disorders were assessed with a Present State Examination
      (PSE) interview analysed with the CATEGO program. With regard to social
      maturation at least half of the patients and controls were doing well, whereas
      for 29% (CI(95), 25%-33%) of the patients and 17% (CI(95), 10%-24%) of the
      controls the index showed delayed maturation. Subjects with poor social
      maturation were found most often among the disabled patients but also among the
      patients without severe diseases. The prevalence of PSE-CATEGO-identified
      psychiatric syndromes was equal in the patients and the controls (22% versus
      20%). However, the patients with severe or disabling diseases had more severe
      psychiatric syndromes. The prevalences of depressive syndromes were also equal,
      but the depression of the patients was more often a profound affective disorder.
      Male sex, poor scholastic and vocational success, and social problems in the
      family during childhood were significantly associated with poor social
      maturation. On the other hand, the most significant predictors of mental health
      problems in young adults were female sex, family distress during childhood, and a
      severe disease. Juvenile-onset physical disease was considered to delay social
      maturation in some subjects and to deepen or modulate the clinical picture of
      mental health disorders. It is concluded that juvenile-onset physical diseases
      combined with family-related factors affect in different ways the social growth
      and psychiatric well-being. The results suggest that the subjects with chronic
      diseases during childhood should be thoroughly assessed by a child psychiatrist
      to evaluate the orientation of psychological development and the impact of the
      child's disease on the family and to ensure balanced psychological and social
      growth.

PMID- 11839114
TI  - Long-term predictive validity of historical factors in two risk assessment
      instruments in a group of violent offenders with schizophrenia.
AB  - The long-term predictive validity of the Violent Risk Appraisal Guide (VRAG) and
      the historical part (H-10) of the risk assessment device HCR-20 in predicting
      violent recidivism was investigated in a sample of (n=106) violent offenders with
      schizophrenia. An effort was made to validate the 9-bin categorization of
      different absolute risk to recidivate depending on the individual score on the
      VRAG. Scores on both devices were retrospectively obtained from various files and
      registers. Individuals were followed up after discharge from hospital for on
      average 86 (standard deviation=19.33) months. During follow-up 29% of the sample
      was reconvicted of a violent crime. Results indicated that both H-10 and VRAG had
      a moderate ability to predict violent recidivism and that H-10 had a slightly
      better accuracy. Most of the items in H-10 but only half of those in VRAG
      correlated significantly with violent recidivism. The 9-bin categorization of
      VRAG scores produced mixed results. In the Swedish sample there was a linear
      trend in which increased VRAG scores were associated with higher absolute risk to
      recidivate. However, the distribution of scores and the figures of absolute risk
      of recidivation were not replicated. It is concluded that historical factors seem
      to play an important role for the long-term prediction of future violence among a
      group of severely mentally ill individuals.

PMID- 11839115
TI  - Behaviour problems in children with dyslexia.
AB  - The association between behaviour problems and dyslexia was assessed in a
      population sample of 10- to 12-year-old children. Twenty-five dyslexic children
      and a matched control group were recruited through a screening in primary schools
      in the city of Bergen, Norway. For the assessment of behaviour problems the Child
      Behavior Checklist (CBCL), Teacher Self Report (TRF), and Youth Self Report (YSR)
      were filled out by parents, teachers, and children, respectively. Information on
      health and developmental factors were obtained from parents on a separate
      questionnaire designed for the study. The dyslexic group had significantly more
      behaviour problems than the control group according to both the CBCL and the TRF.
      On the YSR there was no significant difference between the groups. Dyslexic
      children had higher CBCL and TRF scores on the Total Behaviour Problem scale, the
      Internalizing and Externalizing subdomains, and the Attention problem subscale.
      The groups differed in social background, prenatal risk factors, birth weight,
      preschool language problems, and IQ, but these variables showed no relationship
      to the level of behaviour problems in the present sample. We conclude that pre
      adolescent dyslexic children show a wide range of behaviour problems that cannot
      be attributed to social or developmental background variables.

PMID- 11839117
TI  - Outcome of drug abuse in a 20-year follow-up study of drug-experimenting
      schoolchildren in Finland.
AB  - The fate of 119 drug-experimenting schoolchildren who had been interrogated by
      the narcotics police of Helsinki, Finland, during 1 year, 1971-72, was studied 20
      years later. The material was divided in two groups: those with a favourable
      outcome (n=49) and those with a poor outcome (n=70). Nineteen had died. Criteria
      for poor outcome were death, prison sentence, psychiatric hospitalization, or
      continuation of crimes. The group with a favourable outcome was alive, did not
      have prison sentences or psychiatric hospitalizations, and had not been caught by
      the police after the initial phase of the study. Offences against property in
      early adolescence and intravenous drug use were predictive factors for
      imprisonment, psychiatric hospitalization, and death. A poor atmosphere at home
      and the occupation of the father as labourer were predictive factors for
      imprisonment, psychiatric hospitalization, and death for boys. For girls low
      education was predictive of imprisonment and psychiatric hospitalization. Drug
      use in adolescence is a signal of greater risk for adjustment problems in later
      life.

PMID- 11839116
TI  - Effects of coping skills training, group support, and information for spouses of
      alcoholics: a controlled randomized study.
AB  - Our aim was to compare the effect of three different interventions in spouses of
      alcoholics with regard to coping strategies, mental symptoms, hardship, and
      drinking patterns. The spouses were randomized to three different interventions:
      1) information, 2) individual coping skills training, and 3) group support.
      Follow-up periods were at 12 and 24 months. In this paper the 12-month results
      are presented. Thirty-nine spouses attended the study. They were recruited from
      the services of the Department of Alcohol and Drug Diseases, Malmo University
      Hospital, Malmo, Sweden, and advertisements in the local daily press. The spouses
      were randomized to 1) 1 standard information session, 2) 4 individual coping
      skills training sessions, once a month, and 3) 12 group sessions, twice a month.
      Background data were obtained, and four self-report scales-the Coping Behaviour
      Scale, Hardship Scale, SCL-90, and AUDIT-were administered at admission and
      follow-up examinations. At follow-up all three groups had improved significantly
      with regard to coping behaviour, hardship, and mental symptoms. The coping skills
      training group and the support group together showed a stronger decrease in
      psychiatric symptoms (P = 0.1) than the single information session group. The
      three groups did not differ in coping behaviour and hardship. The findings
      indicate that changing of coping strategies in spouses of alcoholics can be
      successful with only one single information session, whereas the reduction of
      mental symptoms may need longer treatment.

PMID- 11839118
TI  - A study of benzodiazepine users claiming drug-induced psychiatric morbidity.
AB  - To ascertain whether benzodiazepines (BZDs) cause behavioural side effects other
      than those already known or trigger latent mental illness processes, the medical
      records of 32 patients who had submitted claims for BZD-induced side effects to
      the Swedish Pharmaceutical Insurance (SPI) claims office during 1985-92 were re
      assessed by two psychiatrists on the basis of the DSM-IV system to determine
      whether a psychiatric syndrome existed before, during, or after the prescription
      of BZDs. Of the 32 case reports entered into the study, 22 concerned women; mean
      age at the time of SPI claim submission was 47 years, and the mean duration of
      BZD treatment was 11.7 years. The BZD dosages were in most cases within
      recommended therapeutic limits. Twenty-five claimants had also been using other
      psychotropic drugs. In 28 of the 32 cases a psychiatric syndrome in accordance
      with DSM-IV was present before the start of BZD treatment-in most cases an
      anxiety syndrome or anxious personality trait. In the other four cases no
      diagnosis could be given owing to paucity of information. In the 12 cases of
      claimants who fulfilled BZD dependence criteria at some point during treatment,
      withdrawal syndromes might have affected the clinical picture to some extent.
      Four claimants received additional post-BZD-treatment Axis I diagnoses, but in
      all four cases the new diagnoses were clearly related to the pre-existing symptom
      pattern. Thus, apart from the dependence on the drug there was no evidence of
      psychiatric morbidity caused by the BZDs. The symptoms reported by the claimants
      as evidence of BZD-induced psychiatric morbidity seem in most cases to have been
      a feature of pre-existing psychopathology which became more manifest after
      discontinuation of BZD treatment.

PMID- 11839119
TI  - Suicide attempts and serious suicide threats in the city of Riga and resulting
      contacts with medical services.
AB  - The acute treatment of persons attempting suicide is recognized as very important
      in a prevention context. The aim of this study is to describe the medical
      services available to patients who have made suicide attempts or serious threats
      to commit suicide (SAST) within the city of Riga, to trace their passage through
      the various medical facilities, and to estimate SAST rates. Data for 1999 were
      collected from electronic case reports of the Emergency Medical Service (EMS) in
      Riga and monitoring forms of suicide attempters in Riga Psychoneurological
      Hospital (RPH) and Narcological Hospital (NH). In 1999 the first contact with the
      medical service in Riga for 95% of all cases (1024) was the EMS. Of the cases,
      51.8% were treated at the general and 17.0% at the orthopaedic hospital. Of all
      SAST patients 99% have been assessed by at least one psychiatrist, and 43.8% were
      admitted to the psychiatric hospital at some time. The overall rate of suicide
      attempts is 149 per 100 000. The male to female ratio for SAST in Riga for
      individuals aged 15 years and more was 1:0.9. The highest figures were for
      females aged 15-24 and men aged 25-34. Females used poisonings in 75% of cases,
      but males used violent suicide methods in 60% of cases, most often involving
      cutting and associated with the use of alcohol. Data from existing medical
      services provide reasonably good information on the SAST population in Riga City.

PMID- 11839120
TI  - Schizophrenia: a review, with emphasis on the neurodevelopmental hypothesis.
AB  - The neurodevelopmental hypothesis of schizophrenia has gained increasing
      acceptance. This hypothesis assumes a disruption in the normal development of the
      brain, secondary to genetic factors, environmental factors, or, most likely, a
      combination of both. After a brief review of the various aetiologic models since
      the first description of the disease, we review relevant aspects of normal brain
      development and then focus on the pathologic findings supporting the
      neurodevelopmental hypothesis. Although this hypothesis of schizophrenia appears
      to be valid in some cases, it is important to keep in mind that there are many
      cases of schizophrenia in which one finds no documented brain abnormality. It
      therefore seems wrong to speak of schizophrenia in general as a
      neurodevelopmental disorder. It appears that there is a group of patients with
      schizophrenia who fit into a neurodevelopmental model. There is a need to further
      investigate whether these patients can be identified clinically and what this may
      imply with regard to treatment and prognosis.

PMID- 11839122
TI  - Parasuicides without follow-up.
AB  - The aim of this project was to approach subjects who committed parasuicide but
      did not primarily receive or accept a recommendation for care through the regular
      routines after referral to a general hospital. Three hundred and twenty-nine
      consecutive parasuicides in 10- to 89-year-olds (162 men and 167 women) were
      studied. One hundred were subsequently hospitalized in the departments of
      psychiatry, 130 were followed up at outpatient facilities, and 96 left without
      any follow-up. A psychiatric liaison consultation was made in 57% of the total
      sample. The 96 subjects without follow-up were compared with the subjects who
      received follow-up. The sample was somewhat younger and included slightly more
      men. They were single in 54% and unemployed in 43% of the cases. According to the
      DSM-IV, 27% had a concurrent depression. According to the CAGE questions, 57% had
      indication of substance addiction. Fifty-four per cent had currently low global
      functioning, less than 50 points on the GAF. They had not been in contact with
      psychiatric care previously to the same extent as the others. About 34% of these
      who did not receive or rejected follow-up initially after a second approach
      agreed to follow-up when contacted by the project team, referring them to
      appropriate authorities such as social welfare offices, family counselling, or
      psychosocial staff within psychiatry or primary care. This may imply that the
      group delineated is at risk for eventual suicide and that the acceptance of
      follow-up should be interpreted as an indication that a substantial number needs
      help and can be successfully encountered by means of a case manager approach.

PMID- 11839121
TI  - Needs assessed by patients and staff in a Swedish sample of severely mentally ill
      subjects.
AB  - The Psychiatric care reform in Sweden 1995 points out the importance of
      considering the patients' own experienced needs. Earlier research has shown that
      staff and patients differ in their assessment of needs, and the main aim of this
      study was to increase the understanding of these differences. The sample
      consisted of people in the city of Jonkoping, Sweden, with a mental illness that
      cause a disability, influencing daily life. Four hundred and eighty-five patients
      were interviewed, half of them with a diagnosis of schizophrenia. Staff assessed
      the patients' needs by using the Camberwell Assessment of Need. Of the 485
      patients 372 also assessed their own needs with the same instrument. The main
      finding of this study is that staff and patient ratings are not interchangeable.
      Staff rated more needs, both met and unmet, in nearly all areas. The results
      differ from those of earlier British studies. These differences may be due to
      methodologic and cultural circumstances. Decisions about interventions must be
      based on negotiations between staff and patient and should include relatives and
      friends.

PMID- 11839124
TI  - Attachment: a biological basis for the therapeutic relationship?
AB  - When faced with loss, illness, distress, or threat, we tend to seek out an
      attachment figure from which we can obtain comfort and protection. The attachment
      theory, an evolutionary biosocial theory of development, postulates that the
      propensity to make strong emotional bonds to a differentiated and preferred
      person, conceived as stronger and or wiser, is a basic component of the human
      nature, distinct from feeding and sexuality. Attachment behaviour is present in
      germinal form in the neonate and continues to be present "from the cradle to the
      grave". On the basis of day-to-day experience of the responsiveness and
      accessibility of caregivers, children build internal working models of attachment
      figures and of themselves. Expectations about the likely behaviour of others,
      initially preverbal, characterize the approach of the individual to other
      persons. Internal working models are successively modified on the basis of recent
      experience. The therapeutic relationship can be viewed as the seeking of a secure
      base, from which the patient and the therapist, in a joint effort, explore the
      patient's attachment history and the painful feelings associated with it. The
      therapist, responsive to the patient's verbal and non-verbal attachment signals,
      is viewed as a supplementary attachment figure.

PMID- 11839123
TI  - Self-poisonings with drugs by adolescents in the Lund catchment area.
AB  - Our objective was to investigate which drugs young people who attempt suicide use
      in the Lund catchment area-eight municipalities in Skane, southern Sweden. All
      patients aged up to 18 years admitted to Lund University Hospital after
      deliberate or probably deliberate self-poisoning from 1 January 1991 until 31
      December 1995 were included. Forty-nine (58%) had used a single drug; 20 (24%)
      had used 3 or more drugs. Fifty-two (61%) used analgesics-paracetamol was used by
      38 (45%) and propoxyphene by 17 (20%). Thirty-one (36%) had ingested
      psychotropics-13 used benzodiazepines, 10 antidepressants, and 8 antipsychotics.
      Eleven (15%) had used drugs in combination with alcohol. We conclude that it is
      important to follow changes in self-poisoning patterns, to monitor the effects of
      preventive work and discover new trends in drug use.

PMID- 11839125
TI  - Parent-reported competence and emotional and behavioral problems in Finnish
      adolescents.
AB  - This study was part of an 8-year follow-up study of the Epidemiological
      Multicenter Child Psychiatric Study in Finland. The Child Behavior Checklists
      (CBCLs) were analyzed for 598 15- to 16-year-old adolescents living in the
      southwestern area of Finland in 1997. The internal consistency of the CBCL
      syndrome scales was adequate (the alpha coefficient ranged from 0.66 to 0.89).
      The CBCL scores differentiated between non-referred adolescents and adolescents
      who had been referred to the mental health service or had severe problems
      according to the parents. Boys had more externalizing problems than girls in the
      maladjustment group. Girls had more somatic symptoms in the maladjustment group
      than boys.

PMID- 11839126
TI  - The troubled self in women with severe eating disorders (anorexia nervosa and
      bulimia nervosa). A study using interviews, self-reports, and percept-genetic
      methods.
AB  - Fifteen anorectic (A) and 13 bulimic (B) patients aged 20-49 years, all seriously
      ill, and 21 controls were studied, using a half-structured interview, the
      Tennessee Self Concept Scale, the tachistoscopic Identity Test (IT), and two
      other percept-genetic tests. The differences between A and B were not
      particularly pronounced, A patients being on the whole more sensitive and self
      directed, and B patients more depressive and object-directed. The IT
      differentiated between patients and controls very powerfully with regard to
      alexithymia. A type of response in that test, emphasizing the eyes, was seen as a
      search for guidance. Descriptions of mother were generally negative.

PMID- 11839127
TI  - Depression, drinking, and substance use among 14- to 16-year-old Finnish
      adolescents.
AB  - Our aim was to assess the relationship between self-reported depression, alcohol
      consumption, and substance use among 14- to 16-year-olds. A school survey was
      conducted of 16,464 14- to 16-year-olds in two regions of Finland. Alcohol and
      other substance use were found to be significantly associated with depression. Of
      girls (boys) who reported drinking weekly, 24% (13%) scored as depressed,
      compared with 7% (4%) of those not drinking. Of girls (boys) who reported having
      experimented with substances five times or more, 37% (28%) scored as depressed
      compared with 8% (5%) of those who reported never having experimented with
      substances. These associations persisted in multivariate analyses controlling for
      sociodemographic background. In conclusion, frequent drinking and experimenting
      with substances indicate a risk for adolescent depressive disorders, and
      depressive adolescents are at risk for substance use. Health services should pay
      attention to the identified depressive adolescents to prevent the possibly
      subsequent substance use problems among them and also pay attention to frequently
      drinking adolescents and substance experimenters, to increase identification of
      depressive disorder and possibilities for early interventions.

PMID- 11839128
TI  - The hypothalamo-pituitary-adrenal axis in major affective disorder: a review.
AB  - This paper reviews studies of the hypothalamo-pituitary-adrenal (HPA)-axis
      activity in patients with affective disorders. It is concluded that, despite
      methodological drawbacks in most studies, dysregulation of the HPA axis seems to
      be a consistent finding in a proportion of patients with affective disorder. The
      HPA axis is a complex neuroendocrine network with multiple integrated levels of
      control, and it is likely that the dysregulation involves abnormalities at
      several sites within the axis. At present, it is not clear whether the
      abnormalities are related to the affective episodes only or to the disorder
      itself. There is a need for prospective studies of larger samples of patients to
      be followed during successive affective episodes with a combination of
      measurements of the HPA-axis activity and brain imaging.

PMID- 11839129
TI  - Missing data in previously published article.

PMID- 11839130
TI  - Self-reported competence and emotional and behavioral problems in a sample of
      Finnish adolescents.
AB  - The Youth Self-Report (YSR) was completed by 586 15- to 16-year-old Finnish
      adolescents. The internal consistency of the YSR problem scales ranged from 0.61
      to 0.90. Girls reported significantly more internalizing, withdrawn, somatic,
      anxious-depressive thought and attention problems. The adolescent was defined as
      having maladjustment if he she had used mental health services or had more severe
      problems than the peer group according to parent or self-report (11% of the
      sample). There were significant differences at the 0.001 level on all YSR scales
      between maladjustment and non-maladjustment groups. In logistic regression
      analysis anxious-depressive and delinquency scales had the strongest association
      with maladjustment. The results are compared with results from previous
      population-based studies using the YSR in Nordic countries.

PMID- 11839131
TI  - Somatically expressed psychological distress and alexithymia in adolescence-
      reflecting unbearable emotions?
AB  - The characteristics of five 11- to 15-year-old patients with somatic symptoms and
      alexithymia in conjunction with psychological distress are reported. The findings
      are compared with the existing literature. Preceding somatic disorders and
      difficulties at school and in peer relationships were found. Family violence was
      evident in two cases. We postulate that the developmental tasks of adolescence
      were complicated by the threat of disability, disease, and death. The parents
      were incapable of expressing their feelings either in general or because of their
      recent traumatic experiences. Our findings suggest that unbearable emotions often
      precede the combination of preadolescent and adolescent alexithymia and
      somatization in clinically relevant cases.

PMID- 11839132
TI  - Traumatic experiences and posttraumatic stress reactions in children and their
      parents from Kurdistan and Sweden.
AB  - This study was conducted to assess trauma scores and posttraumatic stress
      symptoms among Kurdistanian refugee children and their parents in Sweden and a
      comparable group of Swedish children and their parents. Comparative Kurdistanian
      and Swedish samples composed of 32 children each and their parents were
      interviewed by means of a specially devised trauma instrument (HUTQ-C), to
      identify traumatic events and to measure trauma scores, and with (PTSS-C) and
      (HTQ) to diagnose posttraumatic stress syndrome (PTSD) among children and adults,
      respectively. Although Kurdistanian parents reported considerably more traumatic
      events than Swedish parents, children in both samples showed more similarities
      than differences, both with regard to types and levels of traumatic events.
      Kurdistanian parents showed higher PTSD frequencies than Swedish parents.
      However, these differences proved to be significant with regard to both the
      mother's and the father's lifetime and current PTSD symptom scores. Kurdistanian
      parents have experienced more war traumas and differ with regard to trauma
      exposure and its consequences when compared with Swedish parents. Children from
      the two samples showed more similarities than differences with regard to reported
      trauma and PTSD-related symptoms. These results underline the significance of
      child-specific factors in trauma and PTSD.

PMID- 11839133
TI  - Life situation and posttraumatic symptoms: a follow-up study of refugees from the
      former Yugoslavia living in Sweden.
AB  - Posttraumatic symptoms were assessed by means of the Harvard Trauma Questionnaire
      among 27 severely traumatized refugees from the former Yugoslavia in psychiatric
      treatment and then 3 years later, after an average of 5.5 years in Sweden. At
      follow-up the subjects also answered a questionnaire about their life situations.
      No significant change in average symptom level had taken place at follow-up.
      Seventeen subjects met the DSM IV criteria for posttraumatic stress disorder
      (PTSD) at both times. However, five subjects who met the PTSD criteria in the
      first study did not at follow-up, and the opposite was true for another five
      subjects. Fifteen subjects reported contact with psychiatric care during the past
      year. Unemployment and dependence on social welfare were high at follow-up. The
      unemployment rate of 32% was almost six times greater than that for the regular
      Swedish labor force but comparable to that of the whole Bosnian labor force in
      Sweden. Social contacts with the majority population were as common as with
      compatriots, but two-thirds of the subjects expressed a wish for more social
      contacts outside the family. Positive factors in the subjects' life situations
      were the housing situation and the fact that most subjects had at least
      reasonable knowledge of the majority language. However, a minority of the group
      still had no formal competence in Swedish, with negative consequences for labor
      market integration and social contact with Swedes. Two-thirds of the group had
      made no definite decision to stay in Sweden.

PMID- 11839134
TI  - Assessing depression in drug- and alcohol-dependent subjects: the utility of a
      cognitive-based approach.
AB  - Our objective was to report the development of a measure designed to assess
      depression severity in those with drug and or alcohol problems not confounded by
      somatic items that may more reflect the impact of drug and alcohol problems
      rather than depression itself. A questionnaire was derived with 49 items, each
      assessing cognitive aspects of depression. Subjects with drug and or alcohol
      problems completed the measure and a standard self-report depression inventory
      and were assessed for depression presence and severity by a psychiatrist, who
      used a structured case-finding measure to complement a semi-structured clinical
      assessment. A high percentage of the sample was found to be depressed. Total
      scores on the new measure correlated highly with scores on the two other
      depression reference measures, supporting its validity as a measure of depression
      severity. A refined set of 14 items was also identified as a valid measure of
      depression severity, whereas a determined cut-off established high assignment
      accuracy when examined against the clinical judgement of caseness. In conclusion,
      the refined 14-item set has been validated as a depression measure in those with
      drug and alcohol disorders, whereas the item content may assist clinicians to
      frame screening questions in assessing such patients.

PMID- 11839135
TI  - Determinants of satisfaction with community-based psychiatric services: a cross
      sectional study among schizophrenia outpatients.
AB  - This was a cross-sectional study investigating factors related to satisfaction
      with care among long-term mentally ill patients diagnosed with schizophrenia,
      selected from an outpatient register. Demographic factors, personality variables,
      and health-related factors were related to their satisfaction with care.
      Satisfaction with care showed no relationships to demographic factors such as
      age, living conditions, or civil status. However, significant associations
      indicated that patients who had never been hospitalized for mental illness, who
      were native Swedes, or who had an independent living rated their satisfaction
      with care higher. Personality, measured with the Temperament and Character
      Inventory, showed a relationship to satisfaction with care on only one dimension,
      self-directedness, of seven. Some of the results indicated a relationship between
      subjective measures and satisfaction with care, and some did not, but, taken
      together, the findings suggested a partial influence from a subjective factor on
      both subjective measures of well-being and on satisfaction with care. However,
      associations between interviewer-rated measures of health-related variables and
      satisfaction with care proposed that the better-functioning patients were more
      satisfied with the care, in turn indicating that the services better suited these
      patients. Thus, assuming that the influence of treatment was controlled for
      through the selection of long-term mentally ill subjects, this study pointed to
      two determinants of satisfaction with care: a selectively working subjective
      factor and the services being better designed for the better-functioning
      patients.

PMID- 11839136
TI  - Social phobia: research and clinical practice.
AB  - Social phobia is a pervasive pattern of social inhibition, feelings of
      inadequacy, and hypersensitivity, occurring in about 18% of the clinical
      population. Despite good results with cognitive-behavioural treatment, social
      phobia seems to be a chronic disorder with several complications. The author
      describes an analysis of a divorced woman who was exposed to an early premature
      sexual seduction by her father, abruptly terminated because of an accident. The
      loss of the father was repaired by a delusional system as defence against the re
      emergence of a catastrophic situation. Her compulsion to repeat the traumatic
      situation was seen in symbolic attempts to reproduce the lost experience of
      forbidden pleasure with other men, ending in hopeless affairs. According to DSM
      IV the patient had-besides social phobia-several personality disturbances,
      clinically manifested by weak ego boundaries, an unclear identity, and low self
      esteem. Cognitive-behavioural therapy and psychopharmaca were without any effect.
      The childhood experiences were repeated in the context of the analysis and worked
      through, especially the pre-oedipal and oedipal conflicts. Important repeating
      themes were "crime", guilt, and punishment. After 3 years of analysis it was
      possible for the patient to expose herself to anxiety-producing situations with
      less symptoms. It was possible for her to withdraw the projections and take more
      responsibility for the unconscious sexual and aggressive impulses. At the 5-year
      follow-up her satisfactions had become more realistic and she became involved in
      a positive relationship.

PMID- 11839137
TI  - Dieting and weight concerns among Finnish adolescents.
AB  - The aim of the study was to examine factors associated with dieting and weight
      concerns among Finnish adolescents. A school-survey included a 9-item screening
      scale for assessing attitudes and behaviors involving dieting and body image and
      a self-report measure of the Strengths and Difficulties Questionnaire assessing
      emotional and behavioral problems. Altogether 1458 questionnaires were analyzed,
      which accounted for about 89% of the target population including all the 7th and
      the 9th graders in two cities in Finland. According to the results, dieting and
      weight concerns were extremely common among Finnish adolescents. For all aspects
      of weight control and dieting concerns, the rates of occurrence were greater
      among girls. A high level of dieting concerns was associated with female sex,
      body mass, emotional, conduct, and hyperactivity symptoms, and alcohol use.

PMID- 11839138
TI  - Psychosis and pregnancy: five cases of severely ill women.
AB  - An increasing number of patients with chronic mental disease are now integrated
      in society. As a consequence, women with severe psychiatric illness may become
      pregnant and wish to complete the pregnancy and to give birth to a child. The
      lack of sensation of reality in these patients and their social situation may
      result in particular problems in their treatment, and it may be necessary to
      admit them to a psychiatric ward before delivery. In this paper five cases of
      pregnant women with severe and chronic psychosis are described. These patients
      had many problems in common. Thus, they were all schizophrenics with very severe
      psychopathology, had poor understanding of their own situation, and lacked social
      networks. All the fathers were non-Danish. Coercion was used in all cases. To
      help women with severe mental illness to go through pregnancy and childbirth
      requires close collaboration between psychiatric and obstetric staff and social
      workers, and this should be organized in an institution with experience in the
      treatment of this type of patient.

PMID- 11839139
TI  - Vesaas's The Birds and a patient's history elucidated by means of the theory of
      object relations and the death instinct.
AB  - The psychoanalytical theories of object relations may elucidate both patient
      histories and fictional characters in literature. In this article I apply the
      notions of paranoid-schizoid and depressive positions, projective identification,
      symbolization, communication, and death and life instincts in my understanding of
      the main character Mattis in Vesaas's The Birds and, furthermore, in referring to
      one of my patients. Some literary theory is compared with the theoretical issues
      mentioned above. Comparing Mattis and my patient, I find both differences and
      similarities. The two men are both disabled, albeit to different extents, and
      they are quite aware of this. To be observant of suicidality in these patients
      seems important to me as a clinician, and I find the theory of the death instinct
      valuable in evaluations concerning these matters. I also find The Birds to be of
      importance in the understanding of patients and humanity in general.

PMID- 11839140
TI  - Successful treatment with trazodone for repetitive behavior in schizophrenia.

PMID- 11839141
TI  - Efficacy of trimethoprim-sulfamethoxazole for the prevention of bacterial
      infections in a randomized prophylaxis trial of patients with advanced HIV
      infection.
AB  - We compared the occurrences of several types of infections in HIV-infected
      patients participating in a randomized clinical trial of three treatment
      strategies given for the primary prevention of Pneumocystis carinii pneumonia
      (PCP) and toxoplasmosis. In a phase III open label trial, 842 patients with HIV
      infection and fewer than 200 CD4+ cells/mm(3) received zidovudine (standard dose)
      plus one of three randomly assigned prophylactic agents: trimethoprim
      sulfamethoxazole (TMP-SMZ), or dapsone (DAP), or aerosolized pentamidine (AP).
      Patients developing intolerance to treatment were crossed over to another
      predefined prophylactic therapy. Patients were monitored for infections every
      other week for 8 weeks and then monthly until the study was completed. Primary
      statistical models were proportional hazards models adapted to recurrent end
      points. In an intent-to-treat analysis, compared with AP and DAP, TMP-SMZ
      significantly reduced the risk of any bacterial infection (combining all distinct
      types) (p = 0.02 and p = 0.01, respectively). When considering distinct types
      separately, compared with AP, TMP-SMZ significantly reduced the risk of
      infectious diarrhea (p = 0.04); compared with DAP, AP and TMP-SMZ significantly
      reduced the risk of sinusitis/otitis media (p = 0.03 and p = 0.04, respectively);
      compared with AP and DAP, TMP-SMZ significantly reduced the risk of a second
      occurrence of pneumonia (p = 0.04 and 0.02, respectively). For any bacterial
      infection, infection rates per 100 patient-years of follow-up were 31, 39, and 38
      for TMP-SMZ, DAP, and AP, respectively. In patients with advanced HIV infection
      not taking highly active antiretroviral therapy, the treatment strategy that
      initiates prophylaxis with TMP-SMZ is superior to those initiating with AP or DAP
      for preventing any bacterial infection, with most of the advantage manifested
      through infectious diarrhea, sinusitis/otitis media, and pneumonia.

PMID- 11839143
TI  - CD40-activated macrophages become highly susceptible to X4 strains of human
      immunodeficiency virus type 1.
AB  - Activating cells of the immune system may stimulate human immunodeficiency virus
      type 1 (HIV-1) replication and contribute to select pathogenic variants in vivo.
      Here, we examined the possible effect of a major pathway of immune activation,
      CD40 interaction with its ligand (CD40L), on the susceptibility of monocyte
      derived macrophages (MDMs) to various HIV-1 strains. Stimulation of MDMs with
      CD40L led to reduced replication of R5 HIV-1(Ba-L), whereas this strongly
      enhanced the replication of X4 HIV-1(Lai) as well as of X4 primary isolates, and
      this was associated with strong cytopathic effects. The replication of X4 strains
      was inhibited by stromal cell-derived factor 1, an indication of the restricted
      usage of CXCR4 as virus coreceptor in this case. CD40L induced the activation of
      mitogen-activated protein kinases ERK1/ERK2 and stimulated MDMs to secrete RANTES
      (regulated on activation, normal T cell expressed and secreted), macrophage
      inflammatory protein 1alpha (MIP-1alpha), MIP-1beta, interleukin 6 (IL-6), IL
      1beta, and tumor necrosis factor alpha. From this data, it may be hypothesized
      that activated macrophages represent a favorable environment for the replication
      of classically T lymphocyte-tropic X4 variants and, thus, may contribute
      significantly to the selection of such variants at late stages of clinical HIV-1
      infection.

PMID- 11839142
TI  - Evidence of immune reconstitution in antiretroviral drug-experienced patients
      with advanced HIV disease.
AB  - Highly active antiretroviral therapy (HAART) of HIV disease is associated with
      effective virologic control, immune reconstitution, and clinical improvements.
      This study addresses the potential for improvements in lymphocyte phenotype and
      virologic responses of HIV-infected persons with extensive experience with dual
      nucleoside reverse transcriptase (NRTI) treatment and advanced HIV disease after
      a change to a potent antiretroviral therapy (NRTI + protease inhibitor). The
      majority of participants achieved virologic success. There was a median rise in
      CD4+ lymphocytes of 99 cells/mm(3) by 48 weeks, because of an increase in memory
      CD4+ cells at 4 and 16 weeks, followed by a later increase in naive CD4+ cells
      between weeks 16 and 48. The proportion of activated, DR+ CD38+ CD8+ lymphocytes
      decreased during the 48 weeks of follow-up. The immunologic findings (increased
      memory and naive T cells and reduced activation levels) were significantly
      improved in participants with persistent suppression of viral replication over
      the 48 weeks of the study. Baseline HIV RNA copy number was lower (median, 14,784
      copies/ml) in persons who responded virologically than in those not suppressing
      viral replication (median, 49,454 copies/ml). CD4+ cell counts above the median
      (125/mm(3)) at time 0 for the participants, was the only baseline immunologic
      marker significantly associated with viral suppression at week 48. Participants
      older than 40 years of age demonstrated less immunologic recovery. The results of
      the study show that patients with extensive experience with NRTIs respond both
      virologically and immunologically during the first 48 weeks of therapy with a
      potent antiretroviral regimen.

PMID- 11839144
TI  - Isolation and characterization of replication-competent molecular DNA clones of
      HIV type 1 CRF01_AE with different coreceptor usages.
AB  - We have isolated replication-competent molecular clones of HIV-1 circulating
      recombinant form CRF01_AE with different coreceptor usages. After lambda phage
      cloning of unintegrated circular proviral DNAs derived from a CRF01_AE strain
      (HIV-1NH1), isolated in Japan, the infectious molecular clone, designated p93JP
      NH1, was reconstituted. 93JP-NH1 showed an X4 and R5 phenotype in NP2 cell-based
      coreceptor utilization assays and exerted robust replication in human T cell
      lines, including MT2, M8166, and PM1 cells, whereas it propagated modestly in
      peripheral blood mononuclear cells. The CRF01_AE molecular clone with R5
      phenotype (p93JP-NH2env) was then constructed by replacing the env gene of p93JP
      NH1 with that of a nearly isogenic CRF01_AE R5 strain isolated from an
      epidemiologically linked case. The phylogeny and recombination break-point
      analysis confirmed that these clones shared an A/E recombinant structure similar
      to that of the prototype CRF01_AE strain, CM240. These replication-competent
      CRF01_AE molecular clones with different coreceptor usages would be useful tools
      for the study of CRF01_AE, one of the most prevalent strains in Asia.

PMID- 11839145
TI  - Expression of CD4 controls the susceptibility of THP-1 cells to infection by R5
      and X4 HIV type 1 isolates.
AB  - The monocytic THP-1 cell line has been used to study HIV-monocyte/macrophage
      interactions and the relationship between differentiation, virus production, and
      virus latency. Undifferentiated THP-1 cells are susceptible to infection by T
      tropic human immunodeficiency virus type 1 (HIV-1) isolates that use the
      coreceptor CXCR4 (X4 strains). Treatment with phorbol 12-myristate 13-acetate
      (PMA) induces differentiation of THP-1 cells into adherent macrophage-like cells,
      which are susceptible to M-tropic, CCR5-dependent isolates (R5 strains). The aim
      of this study was to determine whether variabilities observed in the
      susceptibility of THP-1 cells to HIV-1 infection may be related to the
      differential expression of CD4, CCR5, and CXCR4. Both propagation and PMA
      treatment of THP-1 cells resulted in a marked decrease in CD4-positive cells,
      whereas the expression of CCR5 and CXCR4 was not reduced during propagation. Both
      coreceptors were also relatively "resistant" to PMA-induced downregulation when
      compared with the low percentage of CD4-positive cells in differentiated
      cultures. In undifferentiated THP-1 cells, low CD4 expression significantly
      reduced the susceptibility of the cells to infection with the R5 HIV-1(BaL)
      isolate, whereas a PMA-induced decrease in CD4 expression reduced permissiveness
      of the cells to the X4 HIV-1(IIIB) isolate. Thus, cell surface CD4 plays a
      primary role in determining how efficiently THP-1 cells can be infected with the
      X4 and the R5 isolates.

PMID- 11839146
TI  - Codon and amino acid usage in retroviral genomes is consistent with virus
      specific nucleotide pressure.
AB  - Retroviral RNA genomes are known to have a biased nucleotide composition. For
      instance, the plus-strand RNA of human immunodeficiency virus (HIV) is A-rich,
      and the genome of human T cell leukemia virus (HTLV) is C-rich, and other
      retroviruses have a U-rich or G-rich genome. The biased composition of these
      genomes is most likely caused by directional mutational pressure of the
      respective reverse transcriptase enzymes. Using a set of retroviral genomes with
      a distinct nucleotide composition, we performed skew analyses of the nucleotide
      bias along the complete viral genome. Distinct nucleotide signatures were
      apparent, and these typical patterns were generally conserved across the viral
      genome. Furthermore, it is demonstrated that this typical nucleotide bias,
      combined with a profound discrimination against the CpG dinucleotide sequence,
      strongly influences the codon usage of the retroviruses in a direct manner, and
      their amino acid usage in an indirect manner. The fact that both codon usage and
      amino acid usage are so closely entwined with the genome composition has
      important practical implications. For instance, the typical trends in nucleotide
      usage could influence the molecular phylogenetic reconstruction of the family
      Retroviridae.

PMID- 11839147
TI  - CD4+ T cells and monocytes elicited by immunization of rhesus monkeys with
      antigen-pulsed dendritic cells control SIV replication.
AB  - Most HIV infections occur by transmission across mucosal surfaces, where
      dendritic cells (DCs) are the first cells to encounter the virus. Dendritic cells
      are specialized antigen-presenting cells critical for eliciting T cell-mediated
      immune responses. Delayed-type hypersensitivity (DTH) is a cellular immune
      response in some viral infections and it is mediated by CD4+ and/or CD8+ T cells.
      We hypothesized that a DTH response to HIV induced by antigen-pulsed DCs would
      protect against a mucosal exposure to the virus. In a small pilot experiment, six
      rhesus monkeys were immunized with autologous, antigen-pulsed DCs by the
      intradermal route and five of the monkeys were boosted with a second dose of DCs
      at 3 months. Antibody responses to SIV were detected in two of six vaccinated
      monkeys, lymphocyte-proliferative responses were detected in five of the six
      monkeys and cytotoxic T lymphocyte (CTL) responses were detected in four of the
      six monkeys. Using a novel in vitro assay of SIV replication in DCs cocultured
      with autologous CD4+ T cells and monocytes, suppression of viral replication was
      detected from five of the six monkeys at multiple time points before and after
      SIV challenge. Macaques were orally challenged with SIVmac239 at 1-3 months after
      the booster inoculation. Peak viral loads were similar to those of four naive
      animals but, compared with naive monkeys, declined at 6 months to levels 1
      log(10) or more lower in monkeys that had been vaccinated and that had > or = 50%
      suppression of SIV replication in DCs. Optimizing this immunization strategy may
      result in a strong antiviral DTH response that could better control a mucosal
      lentiviral infection.

PMID- 11839148
TI  - Characterization of the South African HIV type 1 subtype C complete 5' long
      terminal repeat, nef, and regulatory genes.
AB  - Human immunodeficiency virus type 1 (HIV-1) subtype C has become the major
      etiological agent in the global and especially African epidemic. To gain better
      understanding of the genetic diversity and rapid transmission of HIV-1 subtype C,
      we have characterized the complete 5' long terminal repeat (LTR) region along
      with the regulatory genes tat and rev as well as the accessory gene nef of 14
      South African HIV-1 subtype C isolates. Phylogenetic analysis revealed a subtype
      C 5' LTR cluster, as well as subclustering of our nef sequences with various
      subtype C strains separate from the India and China subclusters. At least 3 NF
      kappaB sites were present in the 5' LTR of most isolates and 13 isolates had the
      subtype C-specific Rev truncation. Some length variation in exon 2 and the
      absence of a critical cysteine were found in Tat. Residue variation in the
      myristoylation signal and motifs involved in CD4 and MHC-I downregulation was
      recorded in our nef gene sequences.

PMID- 11839149
TI  - HIV type 1 envelope quasispecies in the thymus and lymph Nodes of AIDS patients.
AB  - To test for the presence of HIV syncytium-inducing (SI) strains in the thymus in
      vivo we sequenced HIV envelope V3 variants from thymic and peripheral lymph node
      tissues of three subjects who died of AIDS. Phylogenetic analysis of proviral
      sequences derived by direct sequencing of multiple independent PCRs showed that
      the HIV-1 quasispecies did not segregate into distinct clusters in the thymus
      versus lymph nodes. Examination of env sequences for V3 loop amino acids
      associated with the SI phenotype did not show its preferential localization in
      either thymus or lymph node. One subject harbored only putative SI variants,
      another only putative NSI variants, and the third subject carried a mixture of
      genotypes in both tissues. The thymus and lymph nodes of terminal AIDS patients
      therefore appeared to harbor closely related proviral envelope quasispecies.

PMID- 11839150
TI  - Maintaining low HIV type 1 env genetic diversity among injection drug users
      infected with a B/C recombinant and CRF01_AE HIV type 1 in southern China.
AB  - HIV-1 outbreaks in Guangxi Province, southern China were initiated from two
      separate border cities in 1996 and 1997. Drug users in Pingxiang City, which
      borders Vietnam, were infected with CRF01_AE HIV-1, and drug users in Baise City,
      which borders Yunan Province, were infected with a novel B/C recombinant HIV-1.
      Since 1997, HIV-1 has been rapidly spreading in Guangxi, including its capital
      city Nanning. Survey data indicated that HIV-1 prevalence among IDUs in new
      outbreak regions increased 8 to 42% within 1 year. The B/C recombinants obtained
      from five separate regions in Guangxi, which span a 4-year time frame, were
      remarkable for their low intersubject env V3 diversity, less than 0.2%.
      Similarly, the CRF01_AE from IDUs over a 3-year time frame had low intersubject
      env V3 diversity of less than 1.6%. Different patterns of sequence variations in
      the V3 and V4 regions were observed for the B/C recombinant and the CRF01_AE
      HIV1. The rapid spreading of homogeneous HIV-1 strains in Guangxi may have
      important implications for HIV transmission as well as vaccine development and
      evaluation.

PMID- 11839152
TI  - Impact of viral infection on the gene expression profiles of proliferating normal
      human peripheral blood mononuclear cells infected with HIV type 1 RF.
AB  - Exploiting the power of high-density gene arrays, the simultaneous expression
      analysis of 5600 cellular genes was executed on proliferating peripheral blood
      mononuclear cells (PBMCs) from three normal human donors that were infected in
      vitro with the T cell tropic laboratory strain of HIV-1, RF. Profiles of
      expressed genes were assessed at 1, 12, 24, 48, and 72 hr postinfection and
      compared with those of matched uninfected PBMCs. Viral infection resulted in an
      overall increase in the number of genes expressed with peaks of expression at 1,
      12, and 48 hr postinfection. Functional clustering of genes whose expression
      level in infected PBMCs varied by 2-fold or greater from levels in the controls
      indicated that cellular activation markers, proteins associated with immune cell
      function and with transcription and translation, exhibited increased expression
      subsequent to viral infection. Gene families exhibiting a decline in gene
      expression were confined to the 72 hr time point and included genes associated
      with catabolism and a subset of genes involved with cell signaling and synthetic
      pathways. Self-organizing map (SOM) cluster analysis identified temporal patterns
      of coordinated gene expression in infected PBMCs including genes associated with
      the immune response, the cytoskeleton, and ribosomal subunit structural proteins
      required for protein synthesis.

PMID- 11839153
TI  - CCR5 or CXCR4 is required for efficient infection of peripheral blood mononuclear
      cells by promiscuous human immunodeficiency virus type 2 primary isolates.
AB  - Primary human immunodeficiency virus type 2 (HIV-2) isolates are characterized by
      their ability to use a broad range of coreceptors, including CCR5, CXCR4, and
      several alternative coreceptors. However, the in vivo relevance of this in vitro
      promiscuity in coreceptor usage remains unclear. We set out to evaluate the
      relative importance of CCR5 and CXCR4 for infection of activated peripheral blood
      mononuclear cells (PBMC). PBMC from donors homozygous for wild-type CCR5
      (CCR5(+/+) or CCR5Delta32 (CCR5(-/-)) were tested for their susceptibility to
      infection with 10 primary HIV-2 isolates with known coreceptor usage by parallel
      50% tissue culture infectious dose (TCID50) titrations. Although all isolates,
      except one, were able to establish productive infection in CCR5(-/-) PBMC, the
      infection of these cells was inefficient for all isolates that were unable to use
      CXCR4. For CXCR4-using isolates there were only minor differences in TCID50
      between CCR5(+/+) and CCR5(-/-) PBMC. When we compared the replication kinetics
      in PBMC from donors of the two genotypes we observed an average delay in
      replication onset of 9 days in the CCR5(-/-) PBMC. This study shows that HIV-2
      can use alternative coreceptors for infection of PBMC, but that this infection is
      much less efficient than infection mediated by CCR5 or CXCR4. Thus, CCR5 and
      CXCR4 appear to be the major coreceptors for HIV-2 infection of PBMC.

PMID- 11839154
TI  - Pharmacophore determination of a gp120 C terminal-derived anti-HIV peptide
      construct interfering with membrane fusion suggesting that processing of the
      gp120 C terminus is a prelude to fusion.
AB  - A multiple antigen peptide [CLIV; (PTKAKRR1VVQREKR2)4-K2-K-betaA] from the C
      terminus of the gp120 subunit of HIV Env inhibits Env-mediated cell-to-cell
      fusion through direct interference with the process (Virology 2000;273:169). We
      have examined various CLIV analogs using a cell-to-cell fusion assay, receptor
      binding assays, and molecular modeling to further address the characteristics of
      the peptide responsible for its anti-HIV activity. We show that (1) CLIV does not
      interfere with Env binding to CD4 and does not interact with the binding site of
      Env on CXCR4; (2) CLIV does not inhibit protease activities already reported to
      play a role in fusion; and (3) the pharmacophore is composed of cleavage site1
      with amino acid residues at its C terminal end. Based on our data and on the
      literature, we propose that CLIV interferes with processing of the gp120 C
      terminus at site1 by the lymphocyte surface after CD4 binding. Our hypothesis
      implies that the cleavage region of Env is submitted to a stepwise processing
      including the known intracellular cleavage of gp160 at site2 in order to set the
      activation of the fusion peptide and a yet unexplored cleavage at site1 by the
      target cell surface that triggers fusion.

PMID- 11839151
TI  - Positive association between beta-chemokine-producing T cells and HIV type 1
      viral load in HIV-infected subjects in Abidjan, Cote d'Ivoire.
AB  - The role of beta-chemokines in controlling HIV replication in vivo is still
      controversial. Therefore, the association between HIV-1 plasma viral load and the
      capacity of CD4(+) and CD8(+) T cells to produce beta-chemokines was studied in
      28 antiretroviral drug-naive HIV-1-infected female sex workers in Abidjan, Cote
      d'Ivoire. Percentages of beta-chemokine-positive T cells were measured in
      peripheral blood mononuclear cells by flow cytometry after intracellular staining
      for RANTES (regulated on activation, normal T expressed and secreted), macrophage
      inflammatory protein (MIP)-1alpha, and MIP-1beta. HIV-1-infected subjects had
      higher percentages of MIP-1alpha- and MIP-1beta-positive CD4(+) and CD8(+) T
      cells (p < 0.02) and of RANTES-positive CD8(+) T cells (p = 0.054) than
      uninfected controls. Percentages of RANTES- and MIP-1beta-positive CD8(+) T cells
      correlated directly with HIV-1 plasma viral load (p < 0.02). Percentages of beta
      chemokine-positive CD4(+) and CD8(+) T cells correlated directly with percentages
      of HLA-DR-positive T cells (p < 0.02) and inversely (except RANTES in CD4(+) T
      cells) with absolute numbers of CD4(+) T cells (p < 0.05) in peripheral blood.
      These data indicate that increased percentages of beta-chemokine-producing T
      cells in HIV-1-infected subjects correlate with disease progression and are a
      sign of viremia-driven chronic T cell activation.

PMID- 11839156
TI  - Lack of evidence for infection with simian immunodeficiency virus in bonobos.

PMID- 11839155
TI  - Resistance to tumor necrosis factor-alpha-induced apoptosis in human T
      lymphotropic virus type I-infected T cell lines.
AB  - Induction of apoptosis of virus-infected cells is an important host cell defense
      mechanism. It is well documented that T cells may undergo apoptosis due to
      interactions between Fas and Fas ligand (FasL). In addition, signals that induce
      apoptosis in T cells can result from interaction of tumor necrosis factor (TNF)
      alpha with TNF receptors (TNFRs). It has been shown that human T cell lines
      expressing HTLV-I have decreased sensitivity to Fas-mediated apoptosis. The
      susceptibility of HTLV-I-infected cells to TNF-alpha-induced apoptosis remains to
      be elucidated. In the present study, we examined the expression of TNFRs on HTLV
      I-infected T cell lines that expressed T-cell activation markers and thus
      phenotypically resemble activated T cells. Different from primary activated T
      cells that expressed both TNFRs, none of the five HTLV-I-infected T cell lines
      studied had detectable TNFR1 and only three had TNFR2 on their cell surfaces,
      although, the RNA transcripts of both TNFR genes could be detected via reverse
      transcription-polymerase chain reaction in these cell lines. The T cell blasts,
      which we activated in vitro, were sensitive to apoptosis induced by TNF-alpha and
      by antibodies to TNFR1 and/or TNFR2. However, all of the HTLV-I-infected cell
      lines expressing TNFR2 were resistant to TNF-alpha-mediated apoptosis. These
      findings suggest that HTLV-I infection may interfere with the autonomous suicide
      programs of T cells, not only Fas/FasL but also TNFRs/TNF-alpha pathways, to
      prolong the life of the infected cells. This may contribute to viral persistence
      and favor survival and subsequent expansion of dysregulated infected T cells with
      the potential to produce HTLV-I-associated autoimmune-like diseases or
      malignancies.

PMID- 11839157
TI  - Kinetics of early FIV infection in cats exposed via the vaginal versus
      intravenous route.
AB  - To determine the influence of route of virus exposure on early pathogenesis of
      feline immunodeficiency virus (FIV) infection, cats were exposed to either of two
      FIV isolates (FIV-B-2542 or FIV-A-PPR) by vaginal or intravenous (IV)
      inoculation. Exposure to either virus clade by either route of inoculation
      resulted in vaginal and systemic infection. Peak plasma viremia and tissue
      proviral burden were 1-3 log(10) greater in cats infected with FIV-B-2542 vs. FIV
      A-PPR, irrespective of inoculation route. Plasma RNA levels paralleled provirus
      titers in FIV-B-2542-infected cats and were highest in those exposed IV. In
      contrast, plasma RNA titers were higher in cats infected vaginally with FIV-A-PPR
      than in those infected IV. Despite early differences, PBMC provirus titers were
      similar in all groups by 9 weeks postinfection. In cats infected IV, but not
      vaginally, CD4(+) lymphocyte counts declined significantly independent of the
      magnitude of viremia. Mitogen-induced lymphoproliferation was decreased in all
      infected cats regardless of CD4(+) cell counts; this decline correlated with the
      magnitude of peak plasma viremia in FIV-B-2542, but not FIV-A-PPR, infected cats.
      These results establish that the kinetics of early FIV infection differ with
      route of exposure as well as virus isolate and that properties extrapolated from
      one virus isolate may not be universal.

PMID- 11839158
TI  - Evidence of recombination between 3' and 5' LTRs in macaques inoculated with SIV
      DNA.
AB  - Proviral SIV DNA inoculation of macaques is an efficient method to initiate wild
      type and attenuated SIV infections. However, we found that macaques inoculated
      with SIV DNA engineered to contain a single 105-bp deletion in the 3' nef/LTR
      overlap region had SIV sequences subsequently isolated that had partially or
      fully repaired the deletion with wild-type sequence. Animals inoculated with SIV
      DNA containing identical deletions in both the 5' and 3' LTRs did not repair the
      deletion. Recombination events occurred early, most likely by homologous
      recombination with sequences from the wild-type 5' LTR. This sequence analysis is
      the first demonstration of homologous recombination in vivo following
      administration of a single SIV strain.

PMID- 11839159
TI  - Identification of a new circulating recombinant form of HIV type 1, CRF11-cpx,
      involving subtypes A, G, J, and CRF01-AE, in Central Africa.
AB  - In this study, we characterized three full-length genome sequences with a similar
      mosaic structure from epidemiologically unlinked individuals from Cameroon (97CM
      MP818) and the Central African Republic (99CF-MP1298 and 99CF-MP1307).
      Phylogenetic and recombinant analysis confirmed that the three strains had a
      similar complex recombinant genome, which we can designate now as CRF11-cpx. This
      new CRF was composed of successive fragments of subtype A, G, J, and CRF01-AE.
      The previously reported GR17 virus from a Greek patient infected in the
      Democratic Republic of Congo (DRC) has a similar structure and should be
      considered as the prototype strain of CRF11-cpx. This new CRF circulates in
      Cameroon, Central African Republic, Gabon, and DRC, although the exact
      prevalences remain to be determined.

PMID- 11839160
TI  - Primary HIV infection.
AB  - Primary HIV can be asymptomatic or result in a severe symptomatic illness. Common
      symptoms are pyrexia, pharyngitis, malaise, lethargy, maculopapular rash, mucous
      membrane ulceration, lymphadenopathy and headache. It can be reliably diagnosed
      by a positive virologic test in the absence of HIV-specific antibodies.
      Progression to late-stage disease is influenced by the severity of the symptoms
      in primary HIV infection, the duration of the illness, the presence of
      neurological symptoms and the presence of oral candidiasis. This stage is
      characterized by a very high viral load and infectiousness. Currently the
      experimental data are insufficient to recommend whether or not those diagnosed
      with primary HIV infection should routinely receive antiretroviral therapy.

PMID- 11839161
TI  - Genital mycoplasmas, including Mycoplasma genitalium, as sexually transmitted
      agents.
AB  - Mycoplasmas are the smallest free-living organisms, widespread in nature. Several
      mycoplasma species have been isolated from humans. For 6 of them: Mycoplasma
      hominis, Ureaplasma urealyticum, M. primatum, M. genitalium, M. spermatophilum
      and M. penetrans, the genital tract is the main site of colonization. This review
      is concentrated on the role of mycoplasmas as sexually transmitted agents, with
      the emphasis to M. genitalium infections. M. hominis and U. urealyticum are
      isolated from the genital tract of healthy men and women with considerable
      frequency. The biological features (attachment properties, possible intracellular
      location) and experimental inoculation studies of M. genitalium indicate that
      this mycoplasma has pathogenic potential. Data from case-control studies, looking
      at men with non-gonococcal urethritis and women with cervicitis, have revealed
      that M. genitalium behave similarly to Chlamydia trachomatis and have revealed
      that carriage of M. genitalium and C. trachomatis is usually independent of one
      another. M. genitalium could be considered as a potential cause of sexually
      transmitted urethritis in men, including men with persistent or recurrent
      urethritis. More studies are expected to ascertain the role of M. genitalium in
      the female genital tract. Evidence-based data are needed to decide whether
      current non-gonococcal infection treatment principles are applicable or not for
      M. genitalium infections.

PMID- 11839162
TI  - Why do gay men want to be vaccinated against hepatitis B? An assessment of
      psychosocial determinants of vaccination intention.
AB  - We assessed to what extent gay men are motivated to obtain vaccination against
      hepatitis B virus (HBV), as well as the social cognitive determinants of this
      motivation. A cross-sectional survey was conducted among homosexual men by means
      of a written questionnaire that contained assessments of intention, knowledge and
      social-cognitive determinants of intention (i.e. attitude, social norm and
      perceived behavioural control towards vaccination, perceived severity and
      perceived vulnerability regarding HBV infection). Four hundred and thirty-three
      homosexual men completed the questionnaire. We conducted a linear regression
      analysis to determine the contribution of social-cognitive variables in
      explaining intention to be vaccinated. Attitude, social norm and perceived
      vulnerability were significant predictors of intention. Usually, health education
      emphasizes the severity of a disease, but from this analysis we can conclude that
      gay men should be convinced of their personal vulnerability to HBV, the benefits
      of vaccination, and that important referents of the targeted person think
      positively about vaccination.

PMID- 11839163
TI  - What proportion of episodes of gonorrhoea and chlamydia becomes symptomatic?
AB  - The effectiveness of syndromic treatment as an STD control strategy depends on
      the proportion of episodes which become symptomatic; few studies have measured
      this directly. We estimated these proportions for gonorrhoea (NG) and chlamydia
      (CT), synthesizing data on the point prevalence of self-reported discharge and
      dysuria among infected cases in rural Uganda, the durations of symptoms,
      incubation period and asymptomatic episodes, and the effect of treatment on
      symptom duration. Estimated proportions of episodes that become symptomatic were
      45% for males with NG, 11% for males with CT, 14% for females with NG and 6% for
      females with CT. This was on average 1.5-fold higher than symptom prevalence at
      cross-section among infected cases in this population. Estimates were sensitive
      to assumptions on the relative durations of asymptomatic and symptomatic
      episodes, but were invariably inconsistent with previous direct estimates based
      on a US cohort study. These results show that the probability of recognizing
      symptoms in NG and CT episodes varies between settings. In populations with low
      treatment rates like Uganda, these probabilities can be very low. Here, health
      education should have priority in STD management programmes.

PMID- 11839164
TI  - Does bar-based, peer-led sexual health promotion have a community-level effect
      amongst gay men in Scotland?
AB  - This paper evaluates the effectiveness of a bar-based, peer-led community-level
      intervention to promote sexual health amongst gay men. The intervention consisted
      of peer education within bars, gay specific genitourinary medicine (GUM) services
      and a free-phone hotline. Data were collected at baseline (1996) and at follow-up
      (1999) in gay bars in Glasgow (intervention city) and Edinburgh (control city).
      During the intervention peer educators interacted with 1484 men and new clients
      increased at the gay specific GUM service. However, the hotline was under
      utilized and abused. The outcome measures were: reported hepatitis B vaccination;
      HIV testing; unprotected anal intercourse (UAI) with casual partners; negotiated
      safety; and amongst men reporting UAI with a regular partner, the proportion who
      knew their own and their partner's HIV status. Significant differences in sexual
      health behaviours were observed across locations and across time, but the only
      significant intervention effects were amongst men who had direct contact with the
      intervention, with higher uptake of hepatitis B vaccination and HIV testing. The
      intervention did not produce community-wide changes in sexual health behaviours.
      These results question the replication and transferability of peer-led, community
      level sexual health promotion for gay men outwith the USA and across time.

PMID- 11839165
TI  - One year of Neisseria gonorrhoeae isolates in Sweden: the prevalence study of
      antibiotic susceptibility shows relation to the geographic area of exposure.
AB  - The aim of this study was to compare epidemiological data with antibiotic
      susceptibility patterns, so as to characterize the risk of infection with a
      highly resistant Neisseria gonorrhoeae strain. N. gonorrhoeae strains isolated in
      Sweden from February 1998 through January 1999 were tested for antibiotic
      susceptibility. Epidemiological data were received from each clinician reporting
      a case of gonorrhoea and these data were linked to the N. gonorrhoeae strains. A
      total of 348 N. gonorrhoeae isolates, representing 89% of all Swedish cases
      diagnosed during the 12-month period, were tested for antibiotic susceptibility.
      Of all isolates, 24% were beta-lactamase-producing, and 18% had decreased
      susceptibility to ciprofloxacin (MIC>0.064 mg/l). All isolates were fully
      susceptible to ceftriaxone and spectinomycin. More than 99% of the isolates were
      fully susceptible to azithromycin. The antibiotic susceptibility varied with the
      places where patients were exposed to infection. When exposed in Asia, 63% of the
      isolates showed reduced susceptibility to ciprofloxacin, compared with 0-8.5% of
      the isolates from patients exposed in other places (RR=8.5, P<0.001).
      Ciprofloxacin cannot be recommended as the first choice of treatment if the place
      of exposure was in Asia.

PMID- 11839166
TI  - Genomic diversity of human immunodeficiency virus type-1 in India.
AB  - Surveillance of HIV-1 subtypes has important implications for the development of
      candidate vaccine and understanding the possible differences in the transmission
      and natural history of different subtypes. In this study, HIV-1 subtypes were
      determined for homologies in the C2-V3-V5 region by heteroduplex mobility assay
      (HMA) in HIV-1 seropositive patients referred to the National HIV/AIDS Reference
      Centre, All India Institute of Medical Sciences in New Delhi, India. Of the 125
      samples analysed, 98 (78.4%) were HIV-1 subtype C, 11 (8.8%) were subtype B', 3
      (2.4%) were subtype A and 2 (1.6%) were subtype E. In 11 samples, subtype
      determination was not clear-cut. It is possible that these individuals may be
      infected with recombinant strains of HIV-1. These findings may have significant
      implications for the designing and testing of effective HIV-1 vaccine candidate
      in India.

PMID- 11839167
TI  - Risk factors and cumulative incidence of anaemia among HIV-infected injection
      drug users.
AB  - Risk factors for anaemia and cumulative incidence of anaemia were examined in a
      longitudinal cohort study of 622 injection drug users (IDUs) (8885 visits) in
      Baltimore, Maryland, from 1988 to 2000. At enrollment, 19.6% subjects were
      anaemic (16.1% of men and 30.5% of women, P<0.0001) and 8.4% had microcytic
      anaemia (6.7% of men and 14.0% of women, P=0.006). Cumulative incidence of
      anaemia was 82.2% (87.9% of men and 100% of women, P<0.0001) during a median of
      7.5 years follow-up. Factors associated with anaemia included age (per 5 year
      increase, odds ratio (OR)=1.22; 95% confidence interval (CI): 1.10, 1.36), female
      gender (OR=1.62; 95% CI: 1.16, 2.27), CD4+ lymphocyte count <200 cells/microl (OR
      1.85; 95% CI: 1.52, 2.24), weight loss (OR 1.55; 95% CI: 1.26, 1.91), oral thrush
      (OR 1.53; 95% CI: 1.21, 1.94), Mycobacterium avium complex infection (OR 1.30;
      95% CI: 1.04, 1.64), and zidovudine use (OR 1.24; 95% CI: 1.04, 1.48). Higher
      body mass index (OR 0.92; 95% CI: 0.88, 0.95) and marijuana use (OR 0.75; 95% CI:
      0.61, 0.92) were associated with a lower risk of anaemia. The cumulative
      incidence of anaemia is high among IDUs, and women are at highest risk of
      anaemia.

PMID- 11839168
TI  - Molecular typing of Neisseria gonorrhoeae from hospital and community isolates by
      restriction fragment length polymorphism.
AB  - Strains of Neisseria gonorrhoeae are generally characterized by auxotyping,
      serotyping, plasmid profile, antibiotic sensitivity and deoxyribonucleic acid
      (DNA) amplification fingerprinting. The aim of this study was to analyse the
      generation of restriction fragment length polymorphism (RFLP) patterns by BgIII
      digestion of total genomic DNA of N. gonorrhoeae isolated from the community (n
      =30) and the hospital (n =15) and to establish an association with serogrouping
      and antibiogram. The RFLP patterns produced by BgIII restriction digestion showed
      7 different patterns among 30 community isolates and 9 different patterns among
      15 hospital isolates. 66.7% of isolates belonged to serogroup WI. Penicillin
      resistance was observed in 46.7% of community isolates and 66.7% hospital
      isolates. However, penicillinase producing N. gonorrhoeae (PPNG) were lower in
      the community (6.6%) than in the hospital isolates (53.3%). PPNG strains were
      more often seen in serogroup WI. This is the first Indian report on RFLP genotype
      pattern in N. gonorrhoeae. We noted differences in RFLP genotypes of the
      community (RFLP types 1, 2, 3, 4, 5 and 7) and hospital strains (RFLP types 6 and
      8), while no differences in the serogroup were observed. Ciprofloxacin resistance
      was 20.0% and 26.6% in the community and hospital isolates, respectively.
      Ceftriaxone emerges as the current drug of choice for an effective policy of
      antibiotic treatment of gonorrhoea through syndromic management in developing
      countries.

PMID- 11839169
TI  - Atypical presentation of HIV seroconversion illness in a young woman.
AB  - Early detection and counselling of HIV-infected individuals can have an impact on
      prevention of HIV transmission. We describe an atypical presentation of an HIV
      seroconversion illness in a woman.

PMID- 11839170
TI  - Reiter's syndrome and keratoderma blennorrhagica on glans penis--is this unusual?
AB  - Current teaching on Reiter's syndrome is that keratoderma blennorrhagica lesions
      appear characteristically on the soles of feet, although they can be seen on
      other parts of the body infrequently. We therefore thought that it would be
      interesting to report the case of keratoderma blennorrhagica lesions found on the
      glans penis of a circumcised patient with Reiter's syndrome.

PMID- 11839171
TI  - Shigella sonnei: another cause of sexually acquired reactive arthritis.
AB  - We report a case of reactive arthritis attributable to sexually-acquired Shigella
      sonnei infection. This occurred in the context of an outbreak of S. sonnei among
      homosexually-active men in Sydney, Australia, in 2000.

PMID- 11839173
TI  - Antibiotic-resistant gonorrhoea in a London GUM clinic.

PMID- 11839175
TI  - Utilizing the genome sequence of parasitic protozoa. Papers of a discussion
      meeting at The Royal Society. March 21-22, 2001.

PMID- 11839176
TI  - From genomes to vaccines: Leishmania as a model.
AB  - The 35 Mb genome of Leishmania should be sequenced by late 2002. It contains
      approximately 8500 genes that will probably translate into more than 10 000
      proteins. In the laboratory we have been piloting strategies to try to harness
      the power of the genome-proteome for rapid screening of new vaccine candidate. To
      this end, microarray analysis of 1094 unique genes identified using an EST
      analysis of 2091 cDNA clones from spliced leader libraries prepared from
      different developmental stages of Leishmania has been employed. The plan was to
      identify amastigote-expressed genes that could be used in high-throughput DNA
      vaccine screens to identify potential new vaccine candidates. Despite the lack of
      transcriptional regulation that polycistronic transcription in Leishmania
      dictates, the data provide evidence for a high level of post-transcriptional
      regulation of RNA abundance during the developmental cycle of promastigotes in
      culture and in lesion-derived amastigotes of Leishmania major. This has provided
      147 candidates from the 1094 unique genes that are specifically upregulated in
      amastigotes and are being used in vaccine studies. Using DNA vaccination, it was
      demonstrated that pooling strategies can work to identify protective vaccines,
      but it was found that some potentially protective antigens are masked by other
      disease-exacerbatory antigens in the pool. A total of 100 new vaccine candidates
      are currently being tested separately and in pools to extend this analysis, and
      to facilitate retrospective bioinformatic analysis to develop predictive
      algorithms for sequences that constitute potentially protective antigens. We are
      also working with other members of the Leishmania Genome Network to determine
      whether RNA expression determined by microarray analyses parallels expression at
      the protein level. We believe we are making good progress in developing
      strategies that will allow rapid translation of the sequence of Leishmania into
      potential interventions for disease control in humans.

PMID- 11839177
TI  - Technologies for the study of gene and protein expression in Plasmodium.
AB  - With the imminent completion of the genome sequences of several species of
      Plasmodium, attention is now turning to the exploitation of these genomic
      sequence data for vaccine, drug and diagnostic development. Several technologies
      have been developed over the past decade to assist in the determination of gene
      and protein expression on a global scale. Of these, DNA microarrays, novel high
      throughput proteomic technologies and recombinational cloning technologies are
      lowering the barrier to functional genomic studies in Plasmodium. Of equal
      importance is the capacity to manipulate, store, retrieve and analyse the
      tremendous quantity of data generated from these genomic studies. This paper will
      address the use of these technologies as well as some of the computational tools
      that will be ultimately required to adequately study gene and protein expression
      in Plasmodium.

PMID- 11839178
TI  - Functional genomics: lessons from yeast.
AB  - Functional genomics represents a systematic approach to elucidating the function
      of the novel genes revealed by complete genome sequences. Such an approach should
      adopt a hierarchical strategy since this will both limit the number of
      experiments to be performed and permit a closer and closer approximation to the
      function of any individual gene to be achieved. Moreover, hierarchical analyses
      have, in their early stages, tremendous integrative power and functional genomics
      aims at a comprehensive and integrative view of the workings of living cells. The
      first draft of the human genome sequence has just been produced, and the complete
      genome sequences of a number of eukaryotic human pathogens (including the
      parasitic protozoa Plasmodium, Leishmania, and Trypanosoma) will soon be
      available. However, the most rapid progress in the elucidation of gene function
      will initially be made using model organisms. Yeast is an excellent eukaryotic
      model and at least 40% of single-gene determinants of human heritable diseases
      find homologues in yeast. We have adopted a systematic approach to the functional
      analysis of the Saccharomyces cerevisiae genome. A number of the approaches for
      the functional analysis of novel yeast genes are discussed. The different
      approaches are grouped into four domains: genome, transcriptome, proteome, and
      metabolome. The utility of genetic, biochemical, and physico-chemical methods for
      the analysis of these domains is discussed, and the importance of framing precise
      biological questions, when using these comprehensive analytical methods, is
      emphasized. Finally, the prospects for elucidating the function of protozoan
      genes by using the methods pioneered with yeast, and even exploiting
      Saccharomyces itself, as a surrogate, are explored.

PMID- 11839179
TI  - Functional analysis of Plasmodium falciparum merozoite antigens: implications for
      erythrocyte invasion and vaccine development.
AB  - Malaria is a major human health problem and is responsible for over 2 million
      deaths per year. It is caused by a number of species of the genus Plasmodium, and
      Plasmodium falciparum is the causative agent of the most lethal form.
      Consequently, the development of a vaccine against this parasite is a priority.
      There are a number of stages of the parasite life cycle that are being targeted
      for the development of vaccines. Important candidate antigens include proteins on
      the surface of the asexual merozoite stage, the form that invades the host
      erythrocyte. The development of methods to manipulate the genome of Plasmodium
      species has enabled the construction of gain-of-function and loss-of-function
      mutants and provided new strategies to analyse the role of parasite proteins.
      This has provided new information on the role of merozoite antigens in
      erythrocyte invasion and also allows new approaches to address their potential as
      vaccine candidates.

PMID- 11839181
TI  - Putting the Leishmania genome to work: functional genomics by transposon trapping
      and expression profiling.
AB  - Leishmania are important protozoan pathogens of humans in temperate and tropical
      regions. The study of gene expression during the infectious cycle, in mutants or
      after environmental or chemical stimuli, is a powerful approach towards
      understanding parasite virulence and the development of control measures. Like
      other trypanosomatids, Leishmania gene expression is mediated by a polycistronic
      transcriptional process that places increased emphasis on post-transcriptional
      regulatory mechanisms including RNA processing and protein translation. With the
      impending completion of the Leishmania genome, global approaches surveying mRNA
      and protein expression are now feasible. Our laboratory has developed the
      Drosophila transposon mariner as a tool for trapping Leishmania genes and
      studying their regulation in the form of protein fusions; a classic approach in
      other microbes that can be termed 'proteogenomics'. Similarly, we have developed
      reagents and approaches for the creation of DNA microarrays, which permit the
      measurement of RNA abundance across the parasite genome. Progress in these areas
      promises to greatly increase our understanding of global mechanisms of gene
      regulation at both mRNA and protein levels, and to lead to the identification of
      many candidate genes involved in virulence.

PMID- 11839180
TI  - Mining the Plasmodium genome database to define organellar function: what does
      the apicoplast do?
AB  - Apicomplexan species constitute a diverse group of parasitic protozoa, which are
      responsible for a wide range of diseases in many organisms. Despite differences
      in the diseases they cause, these parasites share an underlying biology, from the
      genetic controls used to differentiate through the complex parasite life cycle,
      to the basic biochemical pathways employed for intracellular survival, to the
      distinctive cell biology necessary for host cell attachment and invasion.
      Different parasites lend themselves to the study of different aspects of parasite
      biology: Eimeria for biochemical studies, Toxoplasma for molecular genetic and
      cell biological investigation, etc. The Plasmodium falciparum Genome Project
      contributes the first large-scale genomic sequence for an apicomplexan parasite.
      The Plasmodium Genome Database (http://PlasmoDB.org) has been designed to permit
      individual investigators to ask their own questions, even prior to formal release
      of the reference P. falciparum genome sequence. As a case in point, PlasmoDB has
      been exploited to identify metabolic pathways associated with the apicomplexan
      plastid, or 'apicoplast' - an essential organelle derived by secondary
      endosymbiosis of an alga, and retention of the algal plastid.

PMID- 11839182
TI  - Orthology between the genomes of Plasmodium falciparum and rodent malaria
      parasites: possible practical applications.
AB  - The work of the consortium that has been formed to complete the entire sequence
      of the genome of a selected clone of the human malaria parasite, Plasmodium
      falciparum, is almost finished. Already huge tracts of the genome are available
      as fully assembled chromosomes or large contigs and the work of initial
      annotation is in an advanced state. Post-genomic research is in one sense the
      process of furthering the process of annotation, creating biological atlases and
      preliminary attempts to make global descriptions of gene transcription and
      proteome analysis are underway. Comparison between significant amounts of genome
      data from both closely, and more distantly related organisms, can facilitate the
      identification of genes themselves, coordinately regulated gene expression
      groups, gene function and genome organization. Models of malaria can fulfil these
      functions and in addition provide an experimental system wherein predictions can
      be tested and basic experimental investigations performed within numerous aspects
      of disease, pathology, parasite-host and parasite-vector interactions.
      Comparative genomics in Plasmodium has already been shown to have informative
      roles in the completion of annotation and the elucidation of gene function. These
      roles will be illustrated by example and used as the basis for a discussion of
      the utility of genome information and malaria models in realizing the desired
      product of Plasmodium genomics, the development of malaria therapies.

PMID- 11839183
TI  - RNA interference: advances and questions.
AB  - In animals and protozoa gene-specific double-stranded RNA triggers the
      degradation of homologous cellular RNAs, the phenomenon of RNA interference
      (RNAi). RNAi has been shown to represent a novel paradigm in eukaryotic biology
      and a powerful method for studying gene function. Here we discuss RNAi in terms
      of its mechanism, its relationship to other post-transcriptional gene silencing
      phenomena in plants and fungi, its connection to retroposon silencing and
      possibly to translation, and its biological role. Among the organisms where RNAi
      has been demonstrated the protozoan parasite Trypanosoma brucei represents the
      most ancient branch of the eukaryotic lineage. We provide a synopsis of what is
      currently known about RNAi in T. brucei and outline the recent advances that make
      RNAi the method of choice to disrupt gene function in these organisms.

PMID- 11839184
TI  - Composition of the editing complex of Trypanosoma brucei.
AB  - The RNA editing that produces most functional mRNAs in trypanosomes is catalysed
      by a multiprotein complex. This complex catalyses the endoribonucleolytic
      cleavage, uridylate addition and removal, and RNA ligation steps of the editing
      process. Enzymatic and in vitro editing analyses reveal that each catalytic step
      contributes to the specificity of the editing and, together with the interaction
      between gRNA and the mRNA, results in precisely edited mRNAs. Tandem mass
      spectrometric analysis was used to identify the genes for several components of
      biochemically purified editing complexes. Their identity and presence in the
      editing complex were confirmed using immunochemical analyses utilizing mAbs
      specific to the editing complex components. The genes for two RNA ligases were
      identified. Genetic studies show that some, but not all, of the components of the
      complex are essential for editing. The TbMP52 RNA ligase is essential for editing
      while the TbMP48 RNA ligase is not. Editing was found to be essential in
      bloodstream form trypanosomes. This is surprising because mutants devoid of genes
      encoding RNAs that become edited survive as bloodstream forms but encouraging
      since editing complex components may be targets for chemotherapy.

PMID- 11839185
TI  - Genetic approaches to studying virulence and pathogenesis in Toxoplasma gondii.
AB  - Toxoplasma gondii is a common protozoan parasite that causes disease in
      immunocompromised humans. Equipped with a wide array of experimental tools, T.
      gondii has rapidly developed as a model parasite for genetic studies. The
      population structure of T. gondii is highly clonal, consisting of three distinct
      lineages that differ dramatically in virulence. Acute virulence is probably
      mediated by the genetic differences that distinguish strain types. We have
      utilized a combination of genetic approaches to investigate the acute virulence
      of toxoplasmosis using the mouse model. These studies reveal the surprising
      finding that pathogenicity is due to the over-stimulation of normally protective
      immune responses. Classical genetic linkage mapping studies indicate that genes
      that mediate acute virulence are linked to chromosome VII in the parasite. To
      increase the resolution of genetic mapping studies, single-nucleotide
      polymorphisms are being developed based on an extensive database of expressed
      sequence tags (ESTs) from T. gondii. Separately, DNA microarray studies are being
      used to examine the expression of parasite and host genes during infection.
      Collectively, these approaches should improve current understanding of virulence
      and pathogenicity in toxoplasmosis.

PMID- 11839186
TI  - Genetic analysis of phenotype in Trypanosoma brucei: a classical approach to
      potentially complex traits.
AB  - The genome of the African trypanosome, Trypanosoma brucei, is currently being
      sequenced, raising the question of how the data generated can be used to
      determine the function of the large number of genes that will be identified.
      There is a range of possible approaches, and in this paper we discuss the use of
      a classical genetic approach coupled with positional cloning based on the ability
      of trypanosomes to undergo genetic exchange. The genetics of these parasites is
      essentially similar to a conventional diploid Mendelian system with allelic
      segregation and an independent assortment of markers on different chromosomes.
      Data are presented showing that recombination occurs between markers on the same
      chromosome allowing the physical size of the unit of recombination to be
      determined. Analysis of the available progeny clones from a series of crosses
      shows that, in principal, large numbers of progeny can readily be isolated from
      existing cryopreserved products of mating and, taking these findings together, it
      is clear that genetic mapping of variable phenotypes is feasible. The available
      phenotypes for analysis are outlined and most are relevant to the transmission
      and pathogenesis of the parasite. Genetic maps from two crosses are presented
      based on the use of the technique of AFLP; these maps comprise 146 and 139
      markers in 30 and 21 linkage groups respectively. Segregation distortion is
      exhibited by some of the linkage groups and the possible reasons for this are
      discussed. The general conclusion, from the results presented, is that a genetic
      mapping approach is feasible and will, in the future, allow the genes determining
      a number of important traits to be identified.

PMID- 11839187
TI  - Metabolic pathway analysis in trypanosomes and malaria parasites.
AB  - Identification of novel drug targets is required for the development of new
      classes of drugs to overcome drug resistance and replace less efficacious
      treatments. In theory, knowledge of the entire genome of a pathogen identifies
      every potential drug target in any given microbe. In practice, the sheer
      complexity and the inadequate or inaccurate annotation of genomic information
      makes target identification and selection somewhat more difficult. Analysis of
      metabolic pathways provides a useful conceptual framework for the identification
      of potential drug targets and also for improving our understanding of microbial
      responses to nutritional, chemical and other environmental stresses. A number of
      metabolic databases are available as tools for such analyses. The strengths and
      weaknesses of this approach are discussed.

PMID- 11839188
TI  - Functional genomics of pathogenic bacteria.
AB  - Microbial diseases remain the commonest cause of global mortality and morbidity.
      Automated-DNA sequencing has revolutionized the investigation of pathogenic
      microbes by making the immense fund of information contained in their genomes
      available at reasonable cost. The challenge is how this information can be used
      to increase current understanding of the biology of commensal and virulence
      behaviour of pathogens with particular emphasis on in vivo function and novel
      approaches to prevention. One example of the application of whole-genome-sequence
      information is afforded by investigations of the pathogenic role of Haemophilus
      influenzae lipopolysaccharide and its candidacy as a vaccine.

PMID- 11839189
TI  - Sutural loosening and skeletal flexibility during growth: determination of drop
      like shapes in sea urchins.
AB  - The shape of sea urchins may be determined mechanically by patterns of force
      analogous to those that determine the shape of a water droplet. This mechanical
      analogy implies skeletal flexibility at the time of growth. Although comprised of
      many rigid calcite plates, sutural collagenous ligaments could confer such
      flexibility if the sutures between plates loosened and acted as joints at the
      time of growth. We present experimental evidence of such flexibility associated
      with weight gain and growth. Over 13-, 4-, and 2-week periods, fed urchins
      (Strongylocentrotus droebachiensis) gained weight and developed looser sutures
      than unfed urchins that maintained or lost weight. Further, skeletons of fed
      urchins force-relaxed more than did those of unfed urchins and urchins with loose
      sutures force-relaxed more than those with tight sutures. Urchins
      (Strongylocentrotus franciscanus) fed for two and a half weeks, gained weight,
      also had looser skeletons and deposited calcite at sutural margins, whereas unfed
      ones did not. In field populations of S. droebachiensis the percentage having
      loose sutures varied with urchin diameter and reflected their size-specific
      growth rate. The association between feeding, weight gain, calcite deposition,
      force relaxation and sutural looseness supports the hypothesis that urchins
      deform flexibly while growing, thus determining their drop-like shapes.

PMID- 11839190
TI  - The irreducible uncertainty of the demography-environment interaction in ecology.
AB  - The interpretation of ecological data has been greatly improved by bridging the
      gap between ecological and statistical models. The major challenge is to separate
      competing hypotheses concerning demography, or other ecological relationships,
      and environmental variability (noise). In this paper we demonstrate that this may
      be an arduous, if not impossible, task. It is the lack of adequate ecological
      theory, rather than statistical sophistication, which leads to this problem. A
      reconstruction of underlying ecological processes can only be done if we are
      certain of either the demographic or the noise model, which is something that can
      only be achieved by an improved theory of stochastic ecological processes.
      Ignoring the fact that this is a real problem may mislead ecologists and result
      in erroneous conclusions about the relative importance of endogenous and
      exogenous factors in natural ecosystems. The lack of correct model identification
      may also have far-reaching consequences for population management and
      conservation.

PMID- 11839191
TI  - On the determinants of population structure in antigenically diverse pathogens.
AB  - Many pathogens exhibit antigenic diversity and elicit strain-specific immune
      responses. This potential for cross-immunity structure in the host resource
      motivates the development of mathematical models, stressing competition for
      susceptible hosts in driving pathogen population dynamics and genetics. Here we
      establish that certain model formulations exhibit characteristics of prototype
      pattern-forming systems, with pathogen population structure emerging as three
      possible patterns: (i) incidence is steady and homogeneous; (ii) incidence is
      steady but heterogeneous; and (iii) incidence shows oscillatory dynamics, with
      travelling waves in strain-space. Results are robust to strain number, but
      sensitive to the mechanism of cumulative immunity.

PMID- 11839192
TI  - A Gondwanan origin of passerine birds supported by DNA sequences of the endemic
      New Zealand wrens.
AB  - Zoogeographic, palaeontological and biochemical data support a Southern
      Hemisphere origin for passerine birds, while accumulating molecular data suggest
      that most extant avian orders originated in the mid-Late Cretaceous. We obtained
      DNA sequence data from the nuclear c-myc and RAG-1 genes of the major passerine
      groups and here we demonstrate that the endemic New Zealand wrens
      (Acanthisittidae) are the sister taxon to all other extant passerines, supporting
      a Gondwanan origin and early radiation of passerines. We propose that (i) the
      acanthisittids were isolated when New Zealand separated from Gondwana (ca. 82-85
      Myr ago), (ii) suboscines, in turn, were derived from an ancestral lineage that
      inhabited western Gondwana, and (iii) the ancestors of the oscines (songbirds)
      were subsequently isolated by the separation of Australia from Antarctica. The
      later spread of passerines into the Northern Hemisphere reflects the northward
      migration of these former Gondwanan elements.

PMID- 11839193
TI  - Cryptic and conspicuous coloration in the pelagic environment.
AB  - Despite the importance of cryptic and conspicuous coloration in pelagic
      ecosystems, few researchers have investigated the optimal reflectance spectra for
      either trait. In this study, the underwater radiance distribution in tropical
      oceanic water was modelled using measured inherent optical properties and
      radiative transfer calculations. The modelled light field was then used to
      predict the reflectance spectra that resulted in minimal or maximal object
      contrast as a function of depth, viewing angle, azimuth and solar elevation. The
      results matched commonly observed trends in the coloration of many pelagic
      organisms and showed that optimal coloration for either crypticity or conspicuity
      is a complex function of the parameters examined. The effects of viewing angle
      and depth were substantial and non-intuitive, showing that red coloration is most
      cryptic at depth. The effects of viewing azimuth were less significant and the
      effects of solar elevation were minor. White coloration and black coloration were
      equally cryptic/conspicuous when viewed from below. Although conspicuous objects
      viewed from below had the lowest contrast when viewed from a short distance, they
      had the longest sighting distances. The contrast of maximally conspicuous objects
      viewed from short distances was greatest at wavelengths displaced from the
      wavelength of maximum light penetration.

PMID- 11839194
TI  - Brighter yellow blue tits make better parents.
AB  - Whether or not bird ornaments are a signal for direct (e.g. good parents) or
      indirect (e.g. good genes) benefits to prospective partners in sexual selection
      is controversial. Carotene coloration in Parus species is directly related to the
      ingestion of caterpillars, so that a brightly carotene-coloured tit may be
      signalling its ability to find caterpillars, a main high-quality food source for
      good fledgling development, and hence its parental abilities. If carotene-based
      plumage coloration is related to the good-parent hypothesis, we predict that
      yellow plumage brightness of tit fathers should be positively correlated to their
      investment in offspring provisioning. Here, we use cross-fostering experiments in
      blue tits (Parus caeruleus) to show that chick development (as measured by tarsus
      length) is related to yellowness of the foster father, but not to that of the
      genetic parents. Using these data, we were able to measure, for the first time to
      our knowledge, the separate contribution of genetic and environmental factors
      (i.e. parental plumage coloration) to chick development, and hence parental
      investment. Our data, which relate carotenoid coloration to models of good
      parents, and data from other authors, which relate ultraviolet coloration to good
      genes models, stress that different kinds of coloration within an individual may
      provide different units of information to prospective females.

PMID- 11839195
TI  - Caste totipotency and conflict in a large-colony social insect.
AB  - In most social insects with large, complex colonies workers and queens are
      morphologically quite distinct. This means that caste determination must occur
      prior to adulthood. However workers and queens in the swarm-founding epiponine
      wasps are often morphologically indistinguishable, or nearly so, suggesting that
      caste determination in these wasps could be quite different. To determine the
      extent of caste lability in the epiponine, Parachartergus colobopterus, we
      removed all the queens from one colony and all but one from another colony.
      Worker aggression diminished after queen removal. A week later the colony with no
      queens had a new, young cohort of mated queens. These must have been either
      adults or pupae at the time of queen removal, and so could not have been fed any
      differently from workers. Relatedness patterns confirmed that these new queens
      would normally have been workers and not queens. A model of inclusive fitness
      interests shows that workers ought to suppress new queen production, except at
      low queen numbers, a prediction supported by our empirical results. The patterns
      of social conflict over queenship resulting from swarm founding in a many-queen
      society may help to explain the unusually weak caste differentiation in the
      epiponines.

PMID- 11839196
TI  - Dose-dependent infection rates of parasites produce the Allee effect in
      epidemiology.
AB  - In many epidemiological models of microparasitic infections it is assumed that
      the infection process is governed by the mass-action principle, i.e. that the
      infection rate per host and per parasite is a constant. Furthermore, the parasite
      induced host mortality (parasite virulence) and the reproduction rate of the
      parasite are often assumed to be independent of the infecting parasite dose.
      However, there is empirical evidence against those three assumptions: the
      infection rate per host is often found to be a sigmoidal rather than a linear
      function of the parasite dose to which it is exposed; and the lifespan of
      infected hosts as well as the reproduction rate of the parasite are often
      negatively correlated with the parasite dose. Here, we incorporate dose
      dependences into the standard modelling framework for microparasitic infections,
      and draw conclusions on the resulting dynamics. Our model displays an Allee
      effect that is characterized by an invasion threshold for the parasite.
      Furthermore, in contrast to standard epidemiological models a parasite strain
      needs to have a basic reproductive rate that is substantially greater than 1 to
      establish an infection. Thus, the conditions for successful invasion of the
      parasite are more restrictive than in mass-action infection models. The analysis
      further suggests that negative correlations of the parasite dose with host
      lifespan and the parasite reproduction rate helps the parasite to overcome the
      invasion constraints of the Allee-type dynamics.

PMID- 11839197
TI  - 'Ancient' DNA in the resting egg bank of a microcrustacean can serve as a
      palaeolimnological database.
AB  - Recent work on the diapausing egg banks of zooplankton, such as Daphnia
      (Crustacea: Anomopoda), indicates that these eggs can remain viable for decades
      while, theoretically, DNA can remain intact for even longer periods (i.e.
      centuries or millennia). We isolated diapausing eggs of Daphnia from a 30 m long
      sediment core taken from a hypereutrophic, northern German lake (Belauer See),
      with some eggs found in dated core material as old as 4500 years. Using
      microsatellite markers, we analysed the genetic structure of the resting eggs
      dated as old as ca. 200 years, and found that, although levels of heterozygosity
      remained remarkably stable, significant genetic differentiation (Nei's D = 0.36;
      F(ST) = 0.15) between recent and 'ancient' resting eggs (including allele
      frequency shifts and private alleles) was detected. These shifts represent either
      species-level changes in this complex (i.e. species-specific characters of
      ephippia are not always robust), or intraspecific shifts in genetic variation, or
      a combination of both. This study demonstrates that the egg banks of aquatic
      zooplankton can serve as repositories of both genetic (intrapopulational) and
      ecological (interspecific) information. The use of molecular markers, such as
      microsatellites, on diapausing egg/seed banks may open new avenues of enquiry
      related to tracking the long-term genetic (and/or species) shifts that are
      associated with long-term environmental changes.

PMID- 11839198
TI  - History and timing of human impact on Lake Victoria, East Africa.
AB  - Lake Victoria, the largest tropical lake in the world, suffers from severe
      eutrophication and the probable extinction of up to half of its 500+ species of
      endemic cichlid fishes. The continuing degradation of Lake Victoria's ecological
      functions has serious long-term consequences for the ecosystem services it
      provides, and may threaten social welfare in the countries bordering its shores.
      Evaluation of recent ecological changes in the context of aquatic food-web
      alterations, catchment disturbance and natural ecosystem variability has been
      hampered by the scarcity of historical monitoring data. Here, we present high
      resolution palaeolimnological data, which show that increases in phytoplankton
      production developed from the 1930s onwards, which parallels human-population
      growth and agricultural activity in the Lake Victoria drainage basin. Dominance
      of bloom-forming cyanobacteria since the late 1980s coincided with a relative
      decline in diatom growth, which can be attributed to the seasonal depletion of
      dissolved silica resulting from 50 years of enhanced diatom growth and burial.
      Eutrophication-induced loss of deep-water oxygen started in the early 1960s, and
      may have contributed to the 1980s collapse of indigenous fish stocks by
      eliminating suitable habitat for certain deep-water cichlids. Conservation of
      Lake Victoria as a functioning ecosystem is contingent upon large-scale
      implementation of improved land-use practices.

PMID- 11839199
TI  - A phylogenetic hypothesis for passerine birds: taxonomic and biogeographic
      implications of an analysis of nuclear DNA sequence data.
AB  - Passerine birds comprise over half of avian diversity, but have proved difficult
      to classify. Despite a long history of work on this group, no comprehensive
      hypothesis of passerine family-level relationships was available until recent
      analyses of DNA-DNA hybridization data. Unfortunately, given the value of such a
      hypothesis in comparative studies of passerine ecology and behaviour, the DNA
      hybridization results have not been well tested using independent data and
      analytical approaches. Therefore, we analysed nucleotide sequence variation at
      the nuclear RAG-1 and c-mos genes from 69 passerine taxa, including
      representatives of most currently recognized families. In contradiction to
      previous DNA-hybridization studies, our analyses suggest paraphyly of suboscine
      passerines because the suboscine New Zealand wren Acanthisitta was found to be
      sister to all other passerines. Additionally, we reconstructed the parvorder
      Corvida as a basal paraphyletic grade within the oscine passerines. Finally, we
      found strong evidence that several family-level taxa are misplaced in the
      hybridization results, including the Alaudidae, Irenidae, and Melanocharitidae.
      The hypothesis of relationships we present here suggests that the oscine
      passerines arose on the Australian continental plate while it was isolated by
      oceanic barriers and that a major northern radiation of oscines (i.e. the
      parvorder Passerida) originated subsequent to dispersal from the south.

PMID- 11839200
TI  - A new view of avian life-history evolution tested on an incubation paradox.
AB  - Viewing life-history evolution in birds based on an age-specific mortality
      framework can explain broad life-history patterns, including the long incubation
      periods in southern latitudes documented here. I show that incubation periods of
      species that are matched phylogenetically and ecologically between Argentina and
      Arizona are longer in Argentina. Long incubation periods have mystified
      scientists because they increase the accumulated risk of time-dependent mortality
      to young without providing a clear benefit. I hypothesize that parents of species
      with low adult mortality accept increased risk of mortality to their young from
      longer incubation if this allows reduced risk of mortality to themselves. During
      incubation, songbird parents can reduce risk of mortality to themselves by
      reducing nest attentiveness (percentage of time on the nest). Here I show that
      parents of species with lower adult mortality exhibit reduced nest attentiveness
      and that lower attentiveness is associated with longer incubation periods.
      However, the incubation period is also modified by juvenile mortality. Clutch
      size variation is also strongly correlated with age-specific mortality.
      Ultimately, adult and juvenile mortality explain variation in incubation and
      other life-history traits better than the historical paradigm.

PMID- 11839202
TI  - Patent Briefing.

PMID- 11839201
TI  - Projecting mechanics into morphospace: disparity in the feeding system of labrid
      fishes.
AB  - In no group of organisms has the link between species richness, morphological
      disparity, disparity in mechanics and functional or ecological diversification
      been made explicit. As a step towards integrating these measures of diversity, we
      examine how the mechanics of the anterior-jaw four-bar linkages of 104 species of
      Great Barrier Reef (GBR) labrid fishes maps into a scale-independent morphospace.
      As predicted from theory, no relationship exists between overall size and the
      mechanics of velocity and force transmission in labrid anterior-jaw linkages.
      Nonetheless, mechanics associated with the anterior jaw appear to have
      constrained diversification of labrid anterior-jaw morphology. Furthermore,
      simulations depict a generally nonlinear relationship between the length of
      individual links and transmission of motion. In addition, no relationship was
      found between morphological disparity and mechanical disparity among the most
      species-rich labrid groups from the GBR. It is also established that regions of
      morphospace equivalent in morphological disparity differ over nearly an order of
      magnitude in mechanical disparity. These results illustrate that without an
      explicit interpretation of the consequences of per unit change in morphology,
      conclusions about diversification drawn only from morphological disparity may be
      misleading.

PMID- 11839203
TI  - Targeting of liposomes to human keratinocytes through adhesive peptides from
      immunoglobulin domains in the presence of IFN-gamma.
AB  - T-cell adhesion is often dictated by the presence of intercellular adhesion
      molecule-1 (ICAM-1) on the target cell surface. Reconstitution of P(0) protein
      into liposomes increases adhesion to melanoma cells expressing ICAM-1. In our
      study, the effect of peptides derived from P(0) protein and leukocyte function
      associated-antigen 1 (LFA-1) on IFN-gamma-stimulated human keratinocytes was
      investigated. Covalently linked P(0)-peptide-1, from the Ig-like domain,
      increased specific liposome binding to IFN-gamma-stimulated keratinocytes in a
      dose-dependent manner. C-terminal-derived P(0)-peptide-3 increased liposome
      binding nonspecifically. LFA-1 and RGD peptides had no apparent effect. P(0)
      peptide-1 is thus a potential targeting ligand for liposomal drug delivery to
      ICAM-1 expressing keratinocytes in inflammatory dermatoses.

PMID- 11839204
TI  - Liposomes containing cationic dimethyl dioctadecyl ammonium bromide: formulation,
      quality control, and lipofection efficiency.
AB  - This article describes a novel, simple, and relatively inexpensive method to
      prepare cationic liposomes using an ethanol injection/pressure extrusion method.
      The study also demonstrated that binding erythrosine dye to cationic liposomes
      results in a shift of the absorption maximum of the dye from 528 nm to 549 nm at
      pH 4.25, allowing quantification and visualization of these vesicles. In
      addition, a relatively simple Ficoll-based gradient centrifugation method for
      separation of lipoplexes from unbound molecules is presented. Laboratory
      formulated dimethyl dioctadecyl ammonium bromide (DDAB) containing liposomes were
      just as efficient in complexing nucleic acids as commercially available types,
      and binding increased as the positive to neutral lipid ratio was increased.
      Transfection efficiency of the DDAB-containing liposomes increased as the ratio
      of cationic to neutral lipid was increased from 1:1 to 4:1 with either PtdChol or
      DOPE as the neutral lipid. A concomitant increase in cytotoxicity of CSU-SA1
      cancer cells was noted as the ratio of positive to neutral lipid of the liposomes
      was increased. Nevertheless, our present study showed that the 2:1 liposome is a
      good choice since it delivers functional plasmids at a comparable rate to
      commercial liposome formulations, has similar toxicities to the less harmful
      commercial liposomes, and is at least 1000-fold more economical to prepare
      inhouse, a major factor to be considered in preclinical and clinical studies with
      these carriers.

PMID- 11839205
TI  - Enantioselective release of controlled delivery granules based on molecularly
      imprinted polymers.
AB  - The objectives of our study were two fold: to examine enantioselective release of
      controlled delivery granules based on molecularly imprinted polymers (MIPs) for
      various racemic drugs, including ibuprofen and ketoprofen (NSAIDs) and
      propranolol (beta-blockers); to evaluate the use of controlled delivery granules
      containing a combination of different MIPs for the multiple simultaneous
      enantioselective-controlled delivery of mixed racemic drugs. In this work, the
      MIP beads selective to S-Ibuprofen, S-ketoprofen, and R-propranolol were prepared
      using multistep swelling and thermal polymerization method. Afterward, the MIP
      beads were formulated with racemate of the chiral drugs and a binder and followed
      by granulation. Then, the enantioselective release of racemic drugs from the
      prepared MIP granules was investigated by an in vitro dissolution test using a
      chiral HPLC for assays of enantiomers. The influence of drug/polymer ratio and
      medium pH on the selective enantiomeric release of MIP granules was explored.
      Further, the release of the enantiomers of racemic ibuprofen and racemic
      ketoprofen from the granule containing two MIPs - S-ibuprofen MIP and S
      ketoprofen MIP - was examined. The release profiles of both S-ibuprofen MIP
      granule and R-propranolol MIP granule exhibited differential release of
      enantiomers. Also, the findings indicated the stereoselective retardation of
      those controlled delivery granules as well as the influence of MIP formulation on
      enantioselective release mechanism. The enantioselective release of S-ibuprofen
      MIP granule and R-propranolol MIP granule appeared to depend on polymer loading
      and medium pH. In this case, the drug/polymer ratio of 1:25 showed the best
      enantioselective release with initial enantiomeric excess of 100%. On the other
      hand, the enantioselectivity of both granules was the greatest in buffer pH 7.4.
      Furthermore, the efficiency in enantioselective release of the combined MIP
      granule was higher than its relative single MIP granules, as a result of the
      cross-reactivities of the MIPs. In our study, controlled delivery granules based
      on MIPs demonstrated significant enantioselective release for several chiral
      drugs, and thus it may be developed as a tool to administer chiral pharmaceutical
      as a single enantiomer.

PMID- 11839206
TI  - Design and fungicidal activity of mucoadhesive lactoferrin tablets for the
      treatment of oropharyngeal candidosis.
AB  - Lactoferrin (Lf) is a potential drug candidate for the treatment of oropharyngeal
      Candida infections. However, for an effective therapeutic treatment an
      appropriate dosage form is required. Therefore a mucoadhesive tablet for buccal
      application was developed. Tablets of sufficient strength could be produced on
      high speed tabletting machines, but they could only be obtained when the protein
      contained at least 7% moisture. The tablet contained sodium alginate both for its
      release-controlling properties as well as for its mucoadhesive properties.
      Furthermore, phosphate buffer was added to keep the pH of the saliva in the mouth
      within the range of 6.5 to 7.5. In this pH range, Lf has shown to have its
      highest activity against Candida growth inhibition. The tablet formulation
      containing Lf had the same antifungal properties as compared with Lf alone,
      because in most cases identical inhibitory concentrations were observed against
      several clinical isolates of Candida albicans and Candida glabrata. In human
      volunteers the tablets, containing 250 mg Lf and placed in each pouch, were able
      to keep the Lf concentration in the saliva at effective levels for at least 2 hr,
      while the pH of the saliva remained within the desired range. We concluded that
      the developed mucoadhesive tablet can improve the therapeutic efficacy of Lf and
      that it is suitable for further clinical research.

PMID- 11839207
TI  - Correlation between the transdermal permeation of ketoprofen and its solubility
      in mixtures of a pH 6.5 phosphate buffer and various solvents.
AB  - The passage of a drug through the skin is directly proportional to the
      concentration of the drug in the donor phase and to the permeability coefficient
      constant Kp. Kp is determined essentially by two factors: the dissolution of the
      drug in the stratum corneum (measured by the partition coefficient P) and the
      diffusion in the same stratum (measured by the diffusion constant D). In our
      study, several saturated solutions of ketoprofen in mixtures of a pH 6.5
      phosphate buffer and various co-solvents were studied to find correlations
      between the solubility of the ketoprofen in the mixtures and its permeation
      parameters in in vitro permeation studies with Franz cells. The results show that
      D does not change in the different mixtures; the diffusion of the drug into the
      stratum corneum is not influenced by the presence of the co-solvents, whereas the
      partition coefficient is strongly influenced. In particular, Kp and P were found
      to be inversely proportional to solubility, meaning that when the co-solvent
      increases the solubility, the partition of the drug and consequently Kp decrease.
      These findings were confirmed in some developed gels, and the developed gels were
      found to enhance the ketoprofen permeation with respect to the formulation in a
      commercial Fastum gel.

PMID- 11839208
TI  - Low concentrations of chlorpromazine and related phenothiazines stimulate gene
      transfer in HeLa cells via receptor-mediated endocytosis.
AB  - Chlorpromazine and related phenothiazine antipsychotic compounds at the low
      concentration of 10(-5) M stimulated luciferase pRSVL DNA uptake and expression
      in HeLa cells. On the other hand, chloroquine at a 10(-5) M was without effect at
      this low concentration. However, at the higher normally used concentration of 10(
      4) M (100 microM), chloroquine strongly stimulated luciferase expression and
      activity. Unfortunately, at 10(-4) M, the phenothiazines were toxic to the cells
      and could not be tested at this concentration. Further experimental work was
      carried out to elucidate the mechanism of action of phenothiazines and
      chloroquine on DNA uptake and expression. Interaction of [3H] pBR 322 DNA with
      chlorpromazine, perphenazine, and chloroquine was studied using these compounds
      as their free bases dissolved in chloroform, followed by their impregnation onto
      Whatman No. 1 filter paper discs. Both phenothiazines on filter paper discs bound
      [3H] pBR 322 DNA to a far greater extent than chloroquine. The method of assay
      (free base) suggests that the major contribution to binding is through
      intercalation. A further possible assay for studying the interaction of
      phenothiazines and chloroquine made use of the ethidium bromide/calf thymus DNA
      intercalation method. Intercalated calf thymus (CT) DNA complexes with ethidium
      bromide (EB) were examined for possible dissociation into free DNA and EB on the
      addition of either chloroquine. SO4 or chlorpromazine.HCl (soluble salts).
      Partial dissociation was observed with both compounds. Further experiments on the
      stability of pBR 322 DNA-polylysine complexes were also carried out using an
      alternative method of assay. Chloroquine (10(-2)-10(-4) M) and chlorpromazine
      (10(-4) M) did not bring about a dissociation of [3H] pBR 322 DNA-polylysine(200)
      complexes when reactions were studied by nitrocellulose filter assays to measure
      released double-stranded DNA. The results indicate that chlorpromazine and
      related phenothiazines stimulate luciferase DNA uptake expression at 10(-5) M.
      Chloroquine at this concentration had practically no effect on expression of
      luciferase activity. Further studies of chloroquine and chlorpromazine on their
      interaction with plasmid DNA as well as DNA-polylysine complexes are reported.

PMID- 11839209
TI  - Bacopasaponin C: critical evaluation of anti-leishmanial properties in various
      delivery modes.
AB  - Bacopasaponin C, an indigenous glycoside, was isolated from Indian medicinal
      plant Bacopa monniera (b. brahmi) and was tested for antileishmanial properties
      both in free and in various delivery modes, e.g., niosomes, microspheres, and
      nanoparticles that are used now as alternatives to more commonly used liposomes.
      The different vesicles were prepared by published protocols. The percent
      intercalation of Bacopasaponin C in liposomes, niosomes, and micropspheres
      determined at its absorption maximal (lambda(max) = 238 nm, epsilon = 8.6 x 10(3)
      M(-1) x cm(-1)) was found to be 30; for nanoparticles it was 50. At equivalent
      dose of 1.75 mg/kg body weight, every third day for a total of 6 doses in 15
      days, Bacopasaponin C in all the vesicular forms was found to be very active. An
      inverse linear relationship between the efficacy and the size of the vesicles was
      established. As analyzed from tissue histology, blood pathology, and specific
      tests related to normal liver and kidney functions, Bacopasaponin C in each of
      the four vesicular forms was found to be without any side effects. Thus, because
      of its indigenous origin and non-toxic nature, Bacopasaponin C could very well be
      considered for application in the clinic through these alternative delivery
      modes.

PMID- 11839212
TI  - Bullet points: new topics in HIV/AIDS.

PMID- 11839213
TI  - Vertigo and abacavir.
AB  - Vertigo can cause significant morbidity and make a person unable to perform
      activities of daily life. A human immunodeficiency virus (HIV)-infected patient
      experienced vertigo while taking abacavir that resolved immediately on cessation
      of therapy. The mechanism by which abacavir appeared to be associated with
      vertigo in this patient is unknown.

PMID- 11839214
TI  - Remembering Luke.
AB  - Nursing is a service that is essential to the promotion, maintenance, and
      restoration of health and well-being. Generally, a systematic approach is put in
      place whereby a client's needs are assessed and care planned, implemented, and
      evaluated. The story of Luke reflects the contrasting approaches to care that
      different nurses bring to their work. Thus, despite a prescribed strategy aimed
      at the restoration of health, a person's individuality makes each nursing case a
      new experience. Luke's death provides many insights into issues such as self
      awareness and personal needs as obviated by someone else's situation. The end of
      his life also illustrate how we perceive one another both in a given situation
      and as time passes.

PMID- 11839215
TI  - Gene therapy of HIV-1 infection using lentiviral vectors expressing anti-HIV-1
      genes.
AB  - The use of vectors based on primate lentiviruses for gene therapy of human
      immunodeficiency virus type 1 (HIV-1) infection has many potential advantages
      over the previous murine retroviral vectors used for delivery of genes that
      inhibit replication of HIV-1. First, lentiviral vectors have the ability to
      transduce dividing and nondividing cells that constitute the targets of HIV-1
      infection such as resting T cells, dendritic cells, and macrophages. Lentiviral
      vectors can also transfer genes to hematopoietic stem cells with a superior gene
      transfer efficiency and without affecting the repopulating capacity of these
      cells. Second, these vectors could be potentially mobilized in vivo by the wild
      type virus to secondary target cells, thus expanding the protection to previously
      untransduced cells. And finally, lentiviral vector backbones have the ability to
      block HIV-1 replication by several mechanisms that include sequestration of the
      regulatory proteins Tat and Rev, competition for packaging into virions, and by
      inhibition of reverse transcription in heterodimeric virions with possible
      generation of nonfunctional recombinants between the vector and viral genomes.
      The inhibitory ability of lentiviral vectors can be further increased by
      expression of anti-HIV-1 genes. In this case, the lentiviral vector packaging
      system has to be modified to become resistant to the anti-HIV-1 genes expressed
      by the vector in order to avoid self-inhibition of the vector packaging system
      during vector production. This review focuses on the use of lentiviral vectors as
      the main agents to mediate inhibition of HIV-1 replication and discusses the
      different genetic intervention strategies for gene therapy of HIV-1 infection.

PMID- 11839216
TI  - Chronic sorrow in the HIV-positive patient: issues of race, gender, and social
      support.
AB  - This study used Olshansky's (1962) concept of chronic sorrow to examine social
      support needs of 21 human immunodeficiency virus (HIV)-positive men and women in
      a southern U.S. city. The methods of inquiry consisted of narrative interviews
      and a quantitative assessment of depression (the Center of Epidemiological
      Studies on Depression [CES-D] Scale). This combined approach indicated that
      chronic sorrow in HIV-positive persons is related to illness, fear of death,
      poverty, and social isolation, especially for women with children. More than half
      of the subjects scored as depressed, with African American women scoring
      significantly higher than Caucasian men or women. Social isolation often resulted
      from the effects of stigma, as framed in Erving Goffman's theory of discredited
      identity. The women were likely to be stigmatized because of their association
      with "dirty sex," contagion, and moral threat in heterosexual communities. Most
      of the men had been protected from the worst effects of stigma because of their
      ties to the gay community and associated health networks. Based on these
      preliminary findings, stigma should be considered a marker of chronic depression
      in the HIV-positive, and support services should take account of the stigmatizing
      contexts of HIV-positive persons.

PMID- 11839217
TI  - Cigarette smoking and the desire to quit among individuals living with HIV.
AB  - Among individuals living with human immunodeficiency virus (HIV), studies have
      found that smokers are at greater risk than nonsmokers to develop bacterial
      pneumonia, oral lesions and acquired immune deficiency syndrome (AIDS) dementia
      complex. Information is lacking regarding the prevalence of cigarette smoking
      among people living with HIV or about their intentions to quit smoking. A survey
      was conducted with a sample of patients attending an HIV outpatient clinic at San
      Francisco General Hospital to assess the prevalence of cigarette smoking and the
      level of interest in quitting. In total, 228 assessments were completed. Study
      results revealed a high percentage of smokers among our sample of individuals
      living with HIV compared to the percentage of smokers found in the general adult
      population. A total of 123 individuals (54%) reported that they smoked
      cigarettes. Men were more than twice as likely to have made previous attempts at
      smoking cessation than were woman. The majority of cigarette smokers (63%)
      reported that they were currently thinking about quitting. Respondents'
      preferences for types of smoking cessation methods are discussed, and
      recommendations are proposed for identifying and treating tobacco dependence in
      this population.

PMID- 11839219
TI  - Observed therapy started in Baltimore.

PMID- 11839220
TI  - TB test approved.

PMID- 11839218
TI  - Physician-patient relationships, patient satisfaction, and antiretroviral
      medication Adherence among HIV-infected adults attending a public health clinic.
AB  - The goal of this project was to explore the connections between human
      immunodeficiency virus (HIV)-positive patients adherence to antiretroviral
      medication treatment regimens and their beliefs about and satisfaction with their
      primary care physicians. In-depth interviews were conducted with 28 HIV-positive
      patients. Results showed that most patients were extremely satisfied with their
      current primary care physicians. When patients were dissatisfied with their care,
      it was often because there was a mismatch between the patient's expectations of
      care and the physician's consultation style. Results also showed that good
      quality physician-patient relationships tended to promote adherence while lesser
      quality relationships impeded it. Findings suggest that strengthening and
      promoting the bonds between physicians and HIV/acquired immunodeficiency syndrome
      (AIDS) patients should be an absolute priority, at both the interpersonal level
      of physician-patient interactions but also at the organizational level.

PMID- 11839221
TI  - Who is in Control?

PMID- 11839222
TI  - Advocacy and activism: missing pieces in the quest to improve end-of-life care.
AB  - Increasing attention has focused on end-of-life care and has identified
      significant deficiencies in access and quality of care. When problems with
      quality or access to care have been identified for other diseases or conditions,
      the public has often responded vigorously. This paper describes two kinds of
      public action that have been effective in improving health care in other areas:
      advocacy and activism. However, a public response to improve end-of-life care has
      been muted. We discuss some of the reasons for this lack of response, and propose
      ways in which providers and funding agencies can work with patients and their
      families to improve end-of-life care.

PMID- 11839223
TI  - On the road to reform: advocacy and activism in end-of-life care.
AB  - This paper argues that the general public is, and should be, an important source
      of activity in end-of-life care reform. Two roles for the public are described:
      personal advocacy and public activism. The first relates to the role of private
      citizens in advocating on their own or a loved one's behalf at the end of life to
      secure quality palliative care. The second relates to the role of leaders in
      mobilizing reform efforts on behalf of the larger society. These roles overlap
      and often function to bolster one another. Numerous examples of how advocacy
      often transforms into activism and how activism relies on advocacy are given,
      drawn from the experience of directing Community-State Partnerships to Improve
      End-of-Life Care, a national program housed at Midwest Bioethics Center in Kansas
      City, Missouri.

PMID- 11839224
TI  - Initial voluntary program standards for fellowship training in palliative
      medicine.
AB  - Initial voluntary standards for fellowship programs in palliative medicine were
      developed through a collaborative process involving the directors of fellowship
      training programs, the American Academy of Hospice and Palliative Medicine
      (AAHPM), and the American Board of Hospice and Palliative Medicine (ABHPM). These
      groups worked with a consultant and representatives from the American Board of
      Medical Specialties (ABMS) and the Accreditation Council for Graduate Medical
      Education (ACGME) to create a training structure for the programs that will
      maximize the likelihood for recognition and accreditation of the subspecialty. An
      accreditation group modeled after an ACGME residency review committee will be
      formed to review and adopt the standards, then accredit programs voluntarily.

PMID- 11839225
TI  - Recommendations to improve end-of-life care through regulatory change in U.S.
      health care financing.
AB  - Palliative care has emerged as the interdisciplinary approach to relieving
      suffering and improving quality of life. Unfortunately, it is not yet available
      to all who need it. Although legislation may ultimately be needed, regulatory
      changes can quickly improve the current situation. While we see many regulatory
      changes that are possible, just three would quickly improve care: adjust hospital
      payment to include essential palliative care services for hospitalized patients
      in pertinent Diagnostic Related Groups (DRGs); clarify physician payment for
      providing palliative care by clarifying guidelines for carriers and paying for
      case management services; and clarify the Medicare Hospice Benefit by defining
      the 6 month prognosis in statistical terms.

PMID- 11839226
TI  - Undergraduate medical palliative care education: a new Canadian perspective.
AB  - Prior to 1 year ago, undergraduate medical palliative medicine education at the
      University of Alberta in Edmonton, Alberta, was limited to a 1-hour didactic
      session and one-half day patient visit. A new integrative curriculum has allowed
      for increased educational exposure to palliative care for medical students. Topic
      content has expanded and different teaching modalities are used to aid learning.
      A highlight of the program is Bus Rounds where small groups of students visit
      terminally ill patients in either a hospice or home setting. After their
      training, the students performed well on two examination questions dealing with
      palliative care issues.

PMID- 11839227
TI  - Physician interactions with families and caregivers after a patient's death:
      current practices and proposed changes.
AB  - There are little objective data concerning physician bereavement or other
      supportive interactions with the families and caregivers of deceased patients. We
      surveyed the physician staff of a large tertiary rural referral center in central
      Pennsylvania. We asked about current practices in attending former patients'
      funerals, family condolence visits, letter or phone contacts, as well as the
      desire of physicians to participate in these activities. The database consisted
      of 143 questionnaires that were returned from 286 physicians initially mailed the
      survey. Only 119 of the 143 had experienced patient deaths in their practices.
      Most of these 119 physicians did not participate in any type of planned contact
      with a former patient's family after the patient's death. Phone calls were used
      39.6% after an inpatient death, and condolence notes were sent by about 40% of
      physicians. There was no correlation between these activities and number of
      deaths in the practice per year or if death occurred as an inpatient or
      outpatient. Physicians practicing at the medical center more than 10 years were
      more likely to contact the grieving family or caregivers. There was significant
      desire by the physicians to have an easy way to identify deceased patients'
      caregivers or loved ones, to have condolence notes available for the physicians'
      use, and to have bereavement service information sent to the families or
      caregivers.

PMID- 11839228
TI  - Why study pain? A qualitative analysis of medical and nursing faculty and
      students' knowledge of and attitudes to cancer pain management.
AB  - Although effective means for pain management have long been available, cancer
      pain remains widely undertreated. Surveys of medical personnel have revealed
      knowledge deficits and attitudinal barriers to pain management, but have not
      determined why such attitudes persist and how they may be addressed in medical
      and nursing curricula. This paper presents findings from a qualitative study of
      the beliefs and attitudes toward pain and cancer pain management held by medical
      and nursing students and faculty who participated in the Cancer Education Module
      for the Management of Pain (CEMMP) project. Analysis centered on informants'
      prioritization and knowledge of pain and cancer pain management and on the
      meanings informants assigned to pain in a clinical context. Themes in
      prioritization included the importance of learning about pain versus cancer pain
      and the responsibility of primary care providers versus specialists for pain and
      cancer pain management. Themes in informants' knowledge of pain included
      knowledge deficits about medications and adjunct therapies and the presence of
      pain management in the curriculum, and the role of knowledgeable faculty members
      and mentors in the dissemination of information about pain management. Themes in
      the meanings informants' assigned to pain included opioidphobia, and the (inter
      )subjectivity of pain. The discussion focuses in particular on tensions within
      the prioritization, knowledge and meanings of pain that must be resolved before
      students can be appropriately educated for optimal pain management.

PMID- 11839229
TI  - Barriers and enablers to hospice referrals: an expert overview.
AB  - BACKGROUND: The nation has an ample supply of hospice programs and, through
      Medicare, Medicaid, or employee-sponsored health insurance, most people have
      nearly full coverage for hospice care. Yet, less than one third of dying persons
      use hospice care. Little is known about what prevents physicians from referring
      to hospice care and how effective hospices are in reaching out to physicians to
      generate referrals. METHODS: In 1999, we conducted in-depth telephone interviews
      with 30 experts in hospice care across the country and made site visits to four
      different hospice programs. RESULTS: The interviewees identified numerous
      barriers to accessing hospice care that are complex and often overlapping. Some
      barriers relate to physicians and other health care professionals, such as their
      difficulty accepting death and their lack of education in end-of-life care. Other
      barriers are the result of patient/family misinformation and aspects of the
      hospice system that limit the number and types of patients deemed appropriate for
      hospice care. Factors that facilitate hospice referrals (which we call enablers)
      are also numerous and include active efforts by hospices to educate and reach out
      to physicians and consumers, as well as physicians' practice styles. CONCLUSIONS:
      The research provided powerful validation of trends that hospice and palliative
      care providers in the trenches have been describing anecdotally for several
      years. Ultimately, this information could be used to develop a toolkit for
      hospices and palliative care organizations to assist them with marketing and
      physician outreach.

PMID- 11839230
TI  - Physicians and hospice care: attitudes, knowledge, and referrals.
AB  - Underutilization of hospice care continues to be a public health issue in the
      United States. Physician barriers related to incorrect knowledge and unfavorable
      attitudes have been hypothesized as part of the explanation. We conducted a mail
      survey of 264 area physicians, obtaining a response rate of 72% (n = 190). The
      survey examined attitudes toward, knowledge about, and perceptions of benefits
      and barriers to hospice care. Physicians demonstrated very positive attitudes
      toward hospice. They had correct knowledge about some aspects of hospice, but
      were uncertain about correct answers on the majority of items. They had erroneous
      knowledge on few items. Physicians perceived many benefits to hospice care, and
      identified patient and family readiness as the major barriers to earlier hospice
      referrals. Demographic and practice variables were related to responses on few of
      the survey items. These findings have many implications for outreach strategies
      for physicians as well as future research.

PMID- 11839231
TI  - Development and implementation of an inpatient acute palliative care service.
AB  - CONTEXT: Although hospice programs are a well-established feature of the American
      medical system, inpatient palliative care services are a recent development.
      Therefore limited data about inpatient palliative care services has been
      published, and no large series has yet been reported. OBJECTIVE: To describe the
      development and implementation, as well as the characteristics and effectiveness,
      of a large inpatient acute palliative care service (APCS). DESIGN, SETTING, AND
      PARTICIPANTS: Data on patient demographics, diagnoses, key symptoms, and outcome
      were collected on each of the 3,712 patients seen from March 1997 to December
      2000 by the APCS in a midwestern urban-suburban three-hospital system. Summary
      statistics were calculated and analyzed. MAIN OUTCOME MEASURES: APCS
      intervention, most common symptoms, and diagnoses, survival, and discharge
      destination. RESULTS: Of the 3,712 patients seen by the APCS, 56.9% were
      transferred to the acute palliative care units (APCU) from elsewhere in the
      hospital, 16.3% were directly admitted to the APCU, and 26.9% were seen in
      consultation by the APCS without transfer to the APCU. The most common symptoms
      were dyspnea (53.9%), weakness (42.5%), and pain (40.8%); 88.7% of patients had
      one to three symptoms. The most frequent diagnoses were cancer (41.3%), cardiac
      disease (17.4%), pulmonary disease (14.0%), and stroke (9.4%). Of all patients
      seen by the APCS, 49.5% survived to discharge, although patients whose primary
      diagnosis was cancer or dementia had significantly higher discharge rates (64.7%
      and 59.6% respectively, p < 0.001). Of those discharged, 72.0% went home or to an
      extended care (ECF) with hospice, 13.8% went to an facility ECF without hospice,
      and 14.2% went home with other home care services. CONCLUSION: Mount Carmel
      Health has developed an APCS and APCU integrated into the mainstream of each of
      its hospitals, providing an opportunity for a more appropriate focus on end-of
      life issues for patients with poor prognoses, intense medical needs, and complex
      family issues.

PMID- 11839232
TI  - Patterns of referral to a palliative care unit: an indicator of different
      attitudes toward the dying patient?
AB  - In 1996 a specialized palliative care unit was opened at the Linkoping University
      Hospital in Sweden and different patterns of referral from different parts of the
      district soon became apparent. The aim of this study was to investigate the
      mechanisms underlying these patterns. During the first 6 months, 133 referrals
      were analyzed. The stated reason for referral and the actual content of care
      were, in each case, classified into five groups: symptom control, terminal care,
      rehabilitation, respite care, and special treatment and investigations. The
      stated reason for referral and the content of care coincided in three groups:
      terminal care, rehabilitation, and special treatment and investigations. When
      symptom control was the stated reason for referral, it was the main content of
      care in only 33 of 78 cases, while terminal care was the actual main content in
      28 of 78 cases. Variations in patterns of referral were also observed in the
      different hospital-based home care teams (HBHC). In our study differences in the
      three HBHC teams regarding knowledge, skill, and attitudes might be reflected in
      variations in patterns of referral. The results illustrate the need for further
      education regarding referral indications, improvements in documentation of reason
      for referral, improved communication between HBHC teams and the palliative care
      unit, and improved prognostication at the end of life.

PMID- 11839233
TI  - Should there be a choice for cardiopulmonary resuscitation when death is
      expected? Revisiting an old idea whose time is yet to come.
AB  - Since closed chest cardiac massage was introduced in 1960, the notion that
      cardiopulmonary resuscitation (CPR) attempts are not appropriate for all patients
      has been consistent. Over the years, leading authorities have clearly articulated
      that for patients who are dying irreversibly and expectedly medical decisions for
      do-not-resuscitate (DNR) orders should be made by physicians, because in such
      cases CPR attempts are not indicated. Physicians are not obligated to and should
      not offer or provide useless treatments, even in the name of patient autonomy.
      Despite this, physicians still seek and obtain patient or proxy consent when CPR
      is not indicated before writing a DNR order. Reasons include fear of legal
      repercussions/misconceptions, limited physician-patient relationships, time
      constraints, and institutional culture. End-of-life plans of care should be based
      on appropriate goals that focus on palliation and not on aggressive medical
      treatments that offer no benefit.

PMID- 11839234
TI  - As individual as death itself: a focus group study of terminal care in nursing
      homes.
AB  - One in four Americans who reach the age of 65 will die in a nursing home, yet
      little research exists to define the end of life care needs of this population.
      We used focus groups with experienced nursing home staff and physicians to: (1)
      define a good death in a nursing home and (2) describe factors that promote or
      prevent good care for the dying in this setting. We audiotaped 11 focus groups
      with 77 participants. Discussions were structured around 3 questions: "How does
      someone die in the nursing home?" "What makes the difference between a good death
      and a bad death?," and "What can aides, nurses, or physicians do to help ensure
      that when someone dies it is a good death?" Participants described lack of
      training, regulatory emphasis on rehabilitation, and a resource-poor setting as
      important barriers to high quality care of the dying in nursing homes. They
      affirmed the value of their experience and personal relationships with residents
      as the basis for good care. Three major themes emerged to define a good death in
      a nursing home: highly individualized care based on continuity relationships with
      caregivers, effective teamwork by staff, physicians and family, and comprehensive
      advance care planning that addresses prognosis, emotional preparation, and
      appropriate use of medical treatments. The significance of these themes may be
      tested in the design of interventions to improve care of the dying in long-term
      care.

PMID- 11839235
TI  - Methadone use in cancer patients with pain: a review.
AB  - In recent years a better understanding of the pharmacologic and pharmacokinetic
      properties of methadone, including equianalgesic ratios has led to its increased
      use as a second line opioid for the treatment of pain in patients with cancer.
      Methadone may be an important alternative for those who have side effects related
      to the use of other opioids because it has no known active metabolites, is well
      absorbed by oral and rectal routes, and also has the advantage of very low cost.
      However, it has a long, unpredictable half-life, which can result in accumulation
      and toxicity in some patients. In addition, rotation to methadone as a second
      line agent is more complex than with other opioids because of its increased
      potency in those patients who are opioid tolerant, particularly those who have
      been on higher doses of other opioids. Future research should address the use of
      methadone as a first-line agent in the management of cancer pain, its use in
      patients with neuropathic pain, and in those who develop rapid tolerance to other
      opioids. In some patients with cancer the long half-life of methadone offers the
      advantage of extended dosing intervals to 12 and even 24 hours, further research
      is also needed in this area.

PMID- 11839236
TI  - Spiritual discernment in palliative care.

PMID- 11839237
TI  - The Grail patient.

PMID- 11839238
TI  - The use of standardized patients in pediatric residency training in palliative
      care: anatomy of a standardized patient case scenario.
AB  - The use of standardized patients (SPs) is an emerging strategy in palliative care
      education. We have used this strategy to provide pediatric residents with a
      structured educational experience focused on effectively communicating bad news
      and concurrently understanding the emotions that they and the parents may
      experience. This article describes the importance of and process for realistic SP
      case development explicitly designed to address predetermined educational goals
      and objectives. Topics addressed include the types of potential SPs that can be
      utilized, their potential strengths and weaknesses, training issues which include
      giving constructive feedback, implementation strategies for the case scenarios
      and evaluation strategies.

PMID- 11839239
TI  - Physician-nurse conflict: can nurses refuse to carry out doctor's orders?

PMID- 11839240
TI  - The introduction of palliative care in Uganda.
AB  - Hospice Uganda was established in Kampala, September 27, 1993. Since then the
      hospice has served over 3,000 patients with cancer, and referrals of patients
      with HIV/AIDS are increasing steadily. The concepts of hospice and palliative
      care are well accepted in Uganda, but the delivery of services has been severely
      constrained by limited resources. Possibilities for growth, both in service
      provision and education of health professionals, were improved significantly with
      the incorporation of palliative care objectives into the Ministry of Health 5
      year strategic plan.

PMID- 11839242
TI  - Windows to the heart: creating an acute care dementia unit.

PMID- 11839246
TI  - Molecular characterization of human monoclonal antibodies derived from fusions of
      tonsil lymphocytes with a human myeloma cell line.
AB  - Recently a new human myeloma cell line (Karpas 707H) has been developed for the
      efficient generation of stable human hybridomas. Here we describe the first
      molecular characterization of human monoclonal antibodies (MAbs) produced by a
      human counterpart to mouse myeloma cells. We studied 30 of the hybridomas
      generated by fusions to tonsil lymphocytes by DNA sequencing of rearranged V
      genes, and have analyzed germ-line diversity, somatic hypermutation, and heavy-
      and light-chain pairings. Our results suggest that the hybridoma-derived
      antibodies are representative of antibodies from populations of human lymphocytes
      and at different stages in the maturation of the response; the use of Karpas 707H
      myeloma for human hybridoma fusions may therefore provide a valuable tool for
      analysis of the human antibody responses.

PMID- 11839247
TI  - AILIM/ICOS: its expression and functional analysis with monoclonal antibodies.
AB  - Activation-inducible lymphocyte immuno-mediatory molecule (AILIM/ICOS) is the
      third member of the co-stimulatory molecule CD28/CTLA-4 (CD152) family, and an
      inducible cell surface glycoprotein expressed on lymphocytes following
      activation. To determine the expression profile of the molecule, we generated
      monoclonal antibodies (MAbs) against human, rat, and mouse AILIM/ICOS. None of
      the MAbs bound to AILIM/ICOS of other species. The numbers of AILIM/ICOS-positive
      cells among human peripheral blood mononuclear cells (PBMC), and rat and mouse
      splenocytes were very low (0.5, 0.4, and 1.2%, respectively), and the cells
      included many CD4-positive T cells except in the case of rat. Rat AILIM/ICOS
      positive cells among splenocytes included many CD45RA-positive B cells, although
      the expression on lymph node cells was similar to that on human PBMC and mouse
      splenocytes. Among rat thymocytes, the AILIM/ICOS expression was mainly localized
      on CD4- and CD8-double positive T cells. The binding of AILIM/ICOS to B7h-Ig,
      which is the ligand-Fc chimeric protein, was inhibited by all AILIM/ICOS-specific
      MAbs except for SG430. The potency of the co-stimulatory activity of CD3 and
      AILIM/ICOS as to T-cell proliferation was found to be substantial in human.
      Interestingly, the levels of stimulation with the two types of MAbs were equal to
      that with CD3 and CD28 despite the different functions of the two MAbs in the
      AILIM/ICOS-B7h interaction. On the other hand, the potencies in rat and mouse,
      although two independent MAbs were tested, were relatively lower than that of
      CD28-mediated co-stimulation.

PMID- 11839248
TI  - Characterization of a phage display-derived human monoclonal antibody (NHS76)
      counterpart to chimeric TNT-1 directed against necrotic regions of solid tumors.
AB  - To eliminate the human anti-mouse antibody (HAMA) response seen in patients
      treated with murine and chimeric antibodies, fully human monoclonal antibodies
      (MAbs) are now being developed. Tumor Necrosis Therapy (TNT) is an approach to
      tumor targeting that utilizes MAbs directed against common intracellular antigens
      such as nucleic acids, accessible only in necrotic areas of solid tumors. By
      binding to the necrotic core of tumors, these TNT MAbs can circumvent many of the
      limitations of MAbs directed against tumor cell surface antigens. Chimeric TNT-1
      (chTNT-1) was first developed from the parent murine antibody by genetically
      engineering the murine variable regions to the human IgG(1) and kappa constant
      regions. Although the chimeric antibody's behavior was similar to that of the
      murine version, the 35% murine homology it shares allows for the potential of a
      HAMA response. A human antibody derived from a phage display library, designated
      NHS76, has been developed with similar binding characteristics to the TNT-1. To
      demonstrate that this genetically engineered human counterpart to chTNT-1 has
      similar pharmacokinetic characteristics, in vivo behavior, and targeting
      abilities, both antibodies were rigorously tested in parallel. For these studies,
      biodistribution analysis in LS174T human colon tumor-bearing nude mice was
      performed to compare the uptake levels in tumor and normal organs. In addition,
      mouse imaging and autoradiographic studies were conducted to demonstrate positive
      uptake in necrotic regions of tumor and negative uptake in viable tissues and
      organs. The results of these studies confirm the comparable nature of both
      antibodies and provide the necessary preclinical data to show the suitability of
      NHS76 as an improved product for the therapy of solid tumors in man.

PMID- 11839249
TI  - Characterization of an anti-MUC1 monoclonal antibody with potential as a cancer
      vaccine.
AB  - The monoclonal antibody (MAb) AR20.5 is a murine MAb, generated against the
      tandem repeat protein backbone of the tumor-associated antigen MUC1. MAb AR20.5
      reacts strongly with either the soluble form or the cell surface epitope of MUC1
      on many human cancer cell lines. It also reacts with a 23-amino acid MUC1
      peptide, E23, which includes the core tandem repeat sequence. Epitope mapping
      confirmed that MAb AR20.5 recognizes a minimum of six residues with the sequence
      DTRPAP. Inhibition of glycosylation of MUC1 resulted in decreased binding of MAb
      AR20.5 to cell surface MUC1, suggesting that MAb AR20.5 binding is carbohydrate
      dependent. The antibody was studied in a human PBL-SCID/beige mouse model to
      evaluate its effect on progression of NIH:OVARCAR-3 tumors. Tumor reduction was
      observed in mice injected with MAb AR20.5, but not in mice treated with control
      murine antibody or PBS (p < 0.001 and p < 0.05, respectively). An anti-tumor
      effect could also be demonstrated in a CB6F1 mouse model with the MUC1
      transfectoma 413BCR.

PMID- 11839250
TI  - Rapid identification of Ralstonia eutropha strain CH34 using monoclonal
      antibodies.
AB  - Ralstonia eutropha strain CH34 (formerly Alcaligenes eutrophus CH34) is an
      aerobic Gram-negative and facultative chemolithotrophic bacteria with plasmid
      bound resistance to heavy metals. The presence of Ralstonia eutropha strain CH34
      is an indication of environmental heavy metals pollution. The major purpose of
      this work was to produce monoclonal antibodies (MAbs) against the metal transport
      outer membrane proteins. In this way, bacteria outer membranes, grown with or
      without iron, were purified. The electrophoretic pattern of the outer membrane
      revealed that, in iron starvation conditions, at least four proteins were
      overexpressed. These outer membranes were used to immunize mice to produce MAbs.
      About 200 hybridomas were tested by enzyme-linked immunoadsorbent assay (ELISA).
      Most of these hybridomas exhibited cross reactions with Escherichia coli and
      Klebsiella aerogenes. Two hybridomas, AE5/7 and AE5/9, produced MAbs that
      detected specifically Ralstonia eutropha strain CH34. Analysis by Western
      blotting showed that these MAbs recognized a protein with a molecular weight of
      about 41 kDa. Moreover, the presence of the two megaplasmids was required for the
      full expression of the 41-kDa protein, as demonstrated by screening of the
      derivatives strains by ELISA. These MAbs could be used for a specific and rapid
      detection of Ralstonia eutropha strain CH34, using direct immunological methods.

PMID- 11839251
TI  - A new monoclonal antibody, P2A8(6), that specifically recognizes a novel epitope
      on the multidrug resistance-associated protein 1 (MRP1), but not on MRP2 nor
      MRP3.
AB  - Multidrug resistance (MDR) is a major problem in the chemotherapeutic treatment
      of cancer. Overexpression of the multidrug resistance-associated protein 1
      (MRP1), is associated with MDR in certain tumors. A number of MRP1-specific MAbs,
      which facilitate both clinical and experimental investigations of this protein,
      are available. To add to this panel of existing antibodies, we have now generated
      an additional MRP1-specific monoclonal antibody (MAb), P2A8(6), which detects a
      unique heat stable epitope on the MRP1 molecule. Female Wistar rats were
      immunized via footpad injections with a combination of two short synthetic
      peptides corresponding to amino acids 235-246 (peptide A) and 246-260 (peptide B)
      of the MRP1 protein. Immune reactive B cells were then isolated from the
      popliteal lymph nodes for fusion with SP2/O-Ag14 myeloma cells. Resultant
      hybridoma supernatants were screened for MRP1-specific antibody production.
      Antibody P2A8(6) was characterized by Western blotting and immunocytochemistry on
      paired multidrug resistant (MRP1 overexpressing) and sensitive parental cell
      lines. The antibody detects a protein of 190 kDa in MRP1-expressing cell lines
      but not in MRP2- or MRP3-transfected cell lines. P2A8(6) stains drug-selected and
      MRP1-transfected cell lines homogeneously by immunocytochemistry and recognizes
      MRP1 by immunohistochemistry on formalin-fixed paraffin wax-embedded tissue
      sections. Peptide inhibition studies confirm that P2A8(6) reacts with peptide B
      (amino acids 246-260), therefore recognizing a different epitope from that of all
      currently available MRP1 MAbs. This new MAb, chosen for its specificity to the
      MRP1 protein, may be a useful addition to the currently available range of MRP1
      specific MAbs.

PMID- 11839252
TI  - Monoclonal antibody G47 engineered to be reactive with colorectal tumor mucin.
AB  - We have previously shown that the normal adult colon produces a sialomucin
      containing the core trisaccharide 1,3 N-acetylgalactosamine. This structure was
      shown to be the epitope for a polyclonal antiserum that demonstrated colon
      "specific" activity. Antiserum binding is dependent upon the presence of O
      acetylated sialic acids present at high concentrations in normal adult colon
      tissue. However, O-acetylation of sialic acids is decreased in colorectal cancer.
      Indeed, approximately 50% of colorectal carcinomas are nonreactive with this
      antiserum. In the current work, we used a de-O-acetylated, normal colon mucin as
      immunogen to generate monoclonal antibody (MAb) G47. Untreated normal colon
      mucins having a high O-acetylated sialic acid content were essentially
      nonreactive with G47. Removal of O-acetyl groups by saponification generated a
      reactive mucin derivative while subsequent treatment with neuraminidase abolished
      reactivity. By immunoperoxidase procedures MAb-G47 was reactive with
      approximately 85% of colorectal tumors while exhibiting relatively low reactivity
      with normal colon tissue. Mucins isolated from normal colon had on average less
      than 10% of the specific epitope as compared with mucins derived from colorectal
      tumors (p < 0.01). Initial immunohistochemical studies on tumors of noncolonic
      origin revealed few positive cases. The potential of MAb-G47 to assist in the
      diagnosis and/or prognosis of colorectal cancer is now being studied.

PMID- 11839253
TI  - Improved production by domain inversion of single-chain Fv antibody fragment
      against high molecular weight proteoglycan for the radioimmunotargeting of
      melanoma.
AB  - Melanoma is among the few cancers with rising incidence. Currently there is no
      effective treatment for metastatic disease, but improved detection of melanoma
      has the potential to benefit the management of patients with early disease.
      Radioimmunodection by imaging with single-chain Fv (scFv) antibody fragments is
      one such emerging diagnostic method. However, the amount of scFv that can be
      produced at a scale suitable for use in patients is limiting. We have previously
      shown that the bacterial expression of a scFv derived from a monoclonal antibody
      (MAb) specific for melanoma-associated proteoglycan can be increased by light
      chain shuffling. In this report we show that a further increase in expression
      yield can be obtained by reversing the usual V(H)-V(L) orientation of scFvs to
      V(L)-V(H). Such seemingly minor changes have previously been reported to have
      unexpected effects on the in vitro and in vivo binding properties of recombinant
      antibodies. Our results show that reversal of the V domain orientation of the
      scFv improves expression by 150% without an adverse effect on melanoma binding in
      vitro and tumor targeting in vivo. Therefore, our results show that alteration of
      V domain orientation can improve the production yield of clinically useful
      antibody fragments. When used in combination with other antibody engineering
      approaches for increased antibody production changing the domain orientation is a
      simple strategy to achieve significant improvements in the production of scFvs
      for tumor radioimmunodetection for patient studies.

PMID- 11839254
TI  - The nucleotide sequence of dinitrophenyl-specific IgE and Fc(epsilon)RI alpha
      subunit obtained from FE-3 hybridoma cells.
AB  - FE-3 cells were established by Hanashiro et al. by hybridizing mouse myeloma
      cells (Sp2/0-Ag14/SF) with rat spleen cells that were freshly isolated from Brown
      Norway rats sensitized with DNP-As. FE-3 cells can constitutively secrete IgE
      without stimulation by cytokines. Our preliminary experiments demonstrated that
      the IgE secretion was decreased at 3 days after start of culture and the addition
      of exogenous IgE into culture media depressed the secretion of IgE. Thus, we
      hypothesized that the IgE production in FE-3 cells may be regulated by a signal
      transduction through the binding of IgE to its high affinity receptor
      (Fc(epsilon)RI) or to an IgE binding protein on the cell surface. In this study,
      we aimed to identify the nucleotide sequence of IgE FE-3 and compared with those
      of mouse IgE and IgE IR162 to find a structural heterogeneity in the Fc region of
      IgE FE-3. We also tested if the mRNA of Fc(epsilon)RI was expressed in FE-3 cells
      using the reverse transcriptase-polymerase chain reaction (RT-PCR) method with
      the combination of sequencing analysis. Consequently, the cDNA sequence of IgE FE
      3 was identical to that of the CH3 and CH4 domains in the epsilon-chain of rat
      IgE IR162, whereas the cDNA of Fc(epsilon)RI was identical to that of mouse,
      suggesting that the genes of IgE FE-3 and Fc(epsilon)RI was derived from that of
      rat spleen cells and mouse myeloma cells, respectively.

PMID- 11839255
TI  - Expression and detection of ScFvB9 and its mutant in recombinant phage antibody
      system.
AB  - Recombinant single-chain antibody (ScFvB9) and its mutant (ScFvB9-6) were
      generated by using a polymerase chain reaction (PCR) from the Fab fragment of the
      murine monoclonal antibody (MAb) B9, MabB9 (gamma2b,kappa), which is specific for
      human plasma apolipoprotein (apo) B-100 of low density lipopreotein (LDL). In the
      recombinant phage antibody system (RPAS), the constructed ScFvB9 and ScFvB9-6
      antibody genes were cloned into the pCANTAB5E phagemid vector and expressed in E.
      coli. The active forms of single-chain antibodies (ScFvB9 and ScFvB9-6) were
      produced as phage-displayed recombinant antibodies or soluble antibody forms in
      E. coli. The activities of ScFvB9 and ScFvB9-6 were confirmed by enzyme-linked
      immunosorbent assay (ELISA) and Western blotting analysis; the generated mutant
      ScFvB9-6 showed slightly higher antigen binding activity than native ScFvB9 as a
      soluble antibody in this RPAS.

PMID- 11839256
TI  - Production of monoclonal antibodies against chicken Pop1 (BVES).
AB  - Pop1 (BVES) is a member of the Popeye gene family which was named for its high
      level expression in the heart and other muscle lineages. However, these proteins
      have no sequence similarity to any other gene family and their function is
      unclear. Here we report the production of recombinant chicken Pop1/BVES protein
      and the generation of two Pop1/BVES specific monoclonal antibodies (MAbs) 3F11-D9
      E8 and 1B3-G11-A8. These antibodies detect recombinant Pop1/BVES in ELISAs and
      endogenous chicken Pop1/BVES in chicken heart extracts by Western blotting.
      Further, both 3F11-D9-E8 and 1B3-G11-A8 detect Pop1/BVES specifically in the
      cardiomyocytes of 8-day-old embryonic chicken hearts by immunofluorescence. These
      MAbs will be useful in immunolocalization and immunoblotting experiments of
      different tissue types to determine the location and levels of Pop1/BVES
      expression throughout development, as well as further analysis of the
      biochemistry of this protein.

PMID- 11839257
TI  - In vitro affinity maturation of human IgM antibodies reactive with tumor
      associated antigens.
AB  - Human lymphocytes secreting tumor cell-specific IgM antibodies were enriched in
      vitro following the stimulation of allogeneic human splenocytes from nontumor
      bearing donors with cytostatic tumor cells or tumor cell plasma membrane
      fractions. The antibodies were generally of the IgM class and displayed low
      intrinsic affinity (K(d) > 100 nM). Nonetheless, the avidity arising from
      multivalent binding sites permitted the identification of multiple monoclonal
      antibodies (MAbs) displaying specificity for cultured tumor cells. Five
      antibodies were cloned from the B cells and two of these were expressed as human
      Fabs with IgG(1) constant regions. Although the avidity of the human IgM
      antibodies was sufficient to permit detection in the original screening, the
      monovalent Fabs displayed low binding activities, consistent with their low
      intrinsic affinity. Thus, in vitro affinity maturation was used to rapidly
      generate multiple variants of both antibodies displaying greater than 100-fold
      higher affinity. Two of the antibodies were characterized further and shown to
      have distinct specificities. One of the targets, LH11238, is associated both with
      the plasma membrane and with lysosomes and is rapidly internalized following
      incubation of the antibody with intact live cell monolayers. The second antigen,
      designated LH13, is a secreted antigen that has been enriched 200-fold from
      conditioned media and consists of two reactive bands at 42 and 45 kDa on
      denaturing Western blots. The stimulation and enrichment of human lymphocytes in
      culture coupled with rapid in vitro affinity maturation of low affinity
      antibodies potentially enables the discovery of human antibodies to a broader
      range of epitopes, including those that might be of greater therapeutic
      relevance.

PMID- 11839258
TI  - A monoclonal antibody against bovine thrombin reacting to the C-terminal side of
      thrombin.
AB  - We succeeded in producing a monoclonal antibody (MAb) against bovine thrombin.
      The MAb belonged to mouse IgG(1), and its light chain consisted of kappa-chain.
      The MAb reacted with bovine and human thrombins, which were coated by coupling to
      poly-lysine-coated wells with glutaraldehyde, but did not react with the thrombin
      like enzyme, habutobin. Furthermore, the MAb did not react with thrombin which
      was coated to plates without poly-lysine and glutaraldehyde. The concentration of
      thrombin in ovalbumin solution (10 mg/mL) could be measured by means of the
      enzyme-linked immunosorbent assay (ELISA) double sandwich method using the MAb
      and polyclonal antibody. Thrombin added to defibrinated plasma could not be
      detected by means of the ELISA double sandwich method using the present MAb, and
      this may be due to the AT-III activity in the defibrinated plasma. Postclotting
      thrombin could be detected by means of the ELISA-double sandwich method using the
      MAb. It is suggested, from the results of our experiments, that the MAb obtained
      reacted in a limited fashion to the C-terminal of bovine thrombin.

PMID- 11839268
TI  - Notch signaling controls cell fate specification along the dorsoventral axis of
      the Drosophila gut.
AB  - BACKGROUND: Gut formation is a key event during animal development. Recent
      genetic analysis in chick, mice, and Drosophila has identified Hedgehog and
      TGFbeta signals as essential players for the development of the primitive gut
      tube along its anterior-posterior (AP) axis. However, the genetic programs that
      control gut patterning along its dorsoventral (DV) axis have remained largely
      elusive. RESULTS: We demonstrate that the activation of the Notch receptor occurs
      in a single row of boundary cells which separates dorsal from ventral cells in
      the Drosophila hindgut. rhomboid, which encodes a transmembrane protein, and
      knirps/knirps-related, which encode nuclear steroid receptors, are Notch target
      genes required for the expression of crumbs, which encodes a transmembrane
      protein involved in organizing apical-basal polarity. Notch receptor activation
      depends on the expression of its ligand Delta in ventral cells, and localizing
      the Notch receptor to the apical domain of the boundary cells may be required for
      proper signaling. The analysis of gene expression mediated by a Notch response
      element suggests that boundary cell-specific expression can be obtained by
      cooperation of Suppressor of Hairless and the transcription factor Grainyhead or
      a related factor. CONCLUSIONS: Our results demonstrate that Notch signaling plays
      a pivotal role in determining cell fates along the DV axis of the Drosophila
      hindgut. The finding that Notch signaling results in the expression of an apical
      polarity organizer which may be required, in turn, for apical Notch receptor
      localization suggests a simple mechanism by which the specification of a single
      cell row might be controlled.

PMID- 11839269
TI  - Contactin supports synaptic plasticity associated with hippocampal long-term
      depression but not potentiation.
AB  - BACKGROUND: Changes in synaptic efficacy are believed to mediate the processes of
      learning and memory formation. Accumulating evidence implicates cell adhesion
      molecules in activity-dependent synaptic modifications associated with long-term
      potentiation (LTP); however, there is no precedence for the selective role of
      this molecule class in long-term depression (LTD). The mechanisms that modulate
      these processes still remain unclear. RESULTS: We report a novel role for
      glycosylphosphatidyl inositol (GPI)-anchored contactin in hippocampal CA1
      synaptic plasticity. Contactin selectively supports paired-pulse facilitation
      (PPF) and NMDA (N-methyl-D-aspartate) receptor-dependent LTD but is not required
      for synaptic morphology, basal transmission, or LTP. Molecular analyses indicate
      that contactin is essential for the membrane and synaptic targeting of the
      contactin-associated protein (Caspr/paranodin) and for the proper distribution of
      a presumptive ligand, receptor protein tyrosine phosphatase beta
      (RPTPbeta)/phosphacan. CONCLUSIONS: These results indicate that contactin plays a
      selective role in synaptic plasticity and identify PPF and LTD, but not LTP, as
      contactin-dependent processes. Engagement of the contactin-Caspr complex with
      RPTPbeta may thus regulate cell-cell interactions contributing to specific
      synaptic plasticity forms.

PMID- 11839270
TI  - The primary visual pathway in humans is regulated according to long-term light
      exposure through the action of a nonclassical photopigment.
AB  - BACKGROUND: The mammalian eye shows marked adaptations to time of day. Some of
      these modifications are not acute responses to short-term light exposure but rely
      upon assessments of the photic environment made over several hours. In the past,
      all attempts at a mechanistic understanding have assumed that these adaptations
      originate with light detection by one or other of the classical photoreceptor
      cells (rods or cones). However, previous work has demonstrated that the mammalian
      eye contains non-rod, non-cone photoreceptors. This study aimed to determine
      whether such photoreceptors contribute to retinal adaptation. RESULTS: In the
      human retina, second-order processing of signals originating in cones takes
      significantly longer at night than during the day. Long-term light exposure at
      night is capable of reversing this effect. Here, we employed the cone ERG as a
      tool to examine the properties of the irradiance measurement pathway driving this
      reversal. Our findings indicate that this pathway (1) integrates irradiance
      measures over time periods ranging from at least 15 to 120 min; (2) responds to
      relatively bright light, having a dynamic range almost entirely outside the
      sensitivity of rods; (3) acts on the cone pathway primarily through a local
      retinal mechanism; and (4) detects light via an opsin:vitamin A photopigment
      (lambda(max) approximately 483 nm). CONCLUSIONS: A photopigment with a spectral
      sensitivity profile quite different from those of the classical rod and cone
      opsins but matching the standard profile of an opsin:vitamin A-based pigment
      drives adaptations of the human primary cone visual pathway according to time of
      day.

PMID- 11839271
TI  - Archaeal guide RNAs function in rRNA modification in the eukaryotic nucleus.
AB  - In eukaryotes, many Box C/D small nucleolar RNAs base pair with ribosomal RNA
      through short complementary guide sequences, thereby marking up to 100 individual
      nucleotides of ribosomal RNA for 2'-O-methylation. Function of the eukaryotic Box
      C/D RNAs depends upon interaction with at least six known proteins. Box C/D RNAs
      are not known to exist in Bacteria but were recently identified in Archaea by
      biochemical analysis and computational genomic screens and have likely evolved
      independently in Archaea and Eukarya for more than 2000 million years. We have
      microinjected Box C/D RNAs from Pyrococcus furiosus, a hyperthermophilic
      archaeon, into the nuclei of oocytes from the aquatic frog Xenopus laevis. Our
      results show that Box C/D RNAs derived from this prokaryote are retained in the
      nucleus, localize to nucleoli, and interact with the X. laevis Box C/D RNA
      binding proteins fibrillarin, Nop56, and Nop58. Furthermore, we have demonstrated
      the ability of archaeal Box C/D RNAs to direct site-specific 2'-O-methylation of
      ribosomal RNA. Our studies have revealed the remarkable ability of archaeal Box
      C/D RNAs to assemble into functional RNA-protein complexes in the eukaryotic
      nucleus.

PMID- 11839272
TI  - Action range of BMP is defined by its N-terminal basic amino acid core.
AB  - During early development, cells receive positional information from neighboring
      cells to form tissue patterns in initially uniform germ layers. Ligands of the
      transforming growth factor (TGF-beta) superfamily are known to participate in
      this pattern formation. In particular, activin has been shown to act as a long
      range dorsalizing signal to establish a concentration gradient in Xenopus. In
      contrast, BMP-2 and BMP-4, other members of the family, appear to influence and
      induce ventral fates only where they are expressed. This raises a question as to
      how the action of BMPs is tightly restricted to the region within and around the
      cells that produce them. Here, we have demonstrated that a basic core of only
      three amino acids in the N-terminal region of BMP-4 is required for its
      restriction to the non-neural ectoderm as its expression domain. Our results also
      suggest that heparan sulfate proteoglycans bind to this basic core and thus play
      a role in trapping BMP-4. The present study is the first to identify the critical
      domain of BMP that is responsible for its interaction with the extracellular
      environment that restricts its diffusion in vivo.

PMID- 11839273
TI  - Two modes of secretion in pancreatic acinar cells: involvement of
      phosphatidylinositol 3-kinase and regulation by capacitative Ca(2+) entry.
AB  - In pancreatic acinar cells, muscarinic agonists stimulate both the release of
      Ca(2+) from intracellular stores and the influx of extracellular Ca(2+). The part
      played by Ca(2+) released from intracellular stores in the regulation of
      secretion is well established; however, the role of Ca(2+) influx in exocytosis
      is unclear. Recently, we observed that supramaximal concentrations of
      acetylcholine (>or=10 microM) elicited an additional component of exocytosis
      despite reducing Ca(2+) influx. In the present study, we found that supramaximal
      exocytosis was substantially inhibited (approximately 70%) by wortmannin (100
      nM), an inhibitor of phosphatidylinositol 3-kinase. In contrast, exocytosis
      evoked by a lower concentration of acetylcholine (1 microM) was potentiated
      (approximately 45%) by wortmannin. Exocytosis stimulated by 1 microM
      acetylcholine in the absence of extracellular Ca(2+) was, like supramaximal
      exocytosis, inhibited by wortmannin. The switch to a wortmannin-inhibitable form
      of exocytosis depended upon a reduction in Ca(2+) entry through store-operated
      Ca(2+) channels, as the switch in exocytotic mode could also be brought about by
      the selective blockade of these channels by Gd(3+) (2 microM), but not by
      inhibition of noncapacitative Ca(2+) entry by SB203580 (10 microM). We conclude
      that supramaximal doses of acetylcholine lead to a switch in the mode of zymogen
      granule exocytosis by inhibiting store-dependent Ca(2+) influx.

PMID- 11839274
TI  - Neurofascin is a glial receptor for the paranodin/Caspr-contactin axonal complex
      at the axoglial junction.
AB  - In myelinated fibers of the vertebrate nervous system, glial-ensheathing cells
      interact with axons at specialized adhesive junctions, the paranodal septate-like
      junctions. The axonal proteins paranodin/Caspr and contactin form a cis complex
      in the axolemma at the axoglial adhesion zone, and both are required to stabilize
      the junction. There has been intense speculation that an oligodendroglial isoform
      of the cell adhesion molecule neurofascin, NF155, expressed at the paranodal loop
      might be the glial receptor for the paranodin/Caspr-contactin complex,
      particularly since paranodin/Caspr and NF155 colocalize to ectopic sites in the
      CNS of the dysmyelinated mouse Shiverer mutant. We report that the extracellular
      domain of NF155 binds specifically to transfected cells expressing the
      paranodin/Caspr-contactin complex at the cell surface. This region of NF155 also
      binds the paranodin/Caspr-contactin complex from brain lysates in vitro. In
      support of the functional significance of this interaction, NF155 antibodies and
      the extracellular domain of NF155 inhibit myelination in myelinating cocultures,
      presumably by blocking the adhesive relationship between the axon and glial cell.
      These results demonstrate that the paranodin/Caspr-contactin complex interacts
      biochemically with NF155 and that this interaction is likely to be biologically
      relevant at the axoglial junction.

PMID- 11839275
TI  - Assembly of epithelial tight junctions is negatively regulated by Par6.
AB  - Epithelial cells display apical-basal polarity, and the apical surface is
      segregated from the basolateral membranes by a barrier called the tight junction
      (TJ). TJs are constructed from transmembrane proteins that form cell-cell
      contacts-claudins, occludin, and junctional adhesion molecule (JAM)-plus
      peripheral proteins such as ZO-1. The Par proteins (partitioning-defective) Par3
      and Par6, plus atypical protein kinase C (aPKC) function in the formation or
      maintenance of TJs and more generally in metazoan cell polarity establishment.
      Par6 contains a PDZ domain and a partial CRIB (Cdc42/Rac interactive binding)
      domain and binds the small GTPase Cdc42. Here, we show that Par6 inhibits TJ
      assembly in MDCK II epithelial cells after their disruption by Ca(2+) depletion
      but does not inhibit adherens junction (AJ) formation. Transepithelial resistance
      and paracellular diffusion assays confirmed that assembly of functional TJs is
      delayed by Par6 overexpression. Strikingly, the isolated, N-terminal fragment of
      PKCzeta, which binds Par6, also inhibits TJ assembly. Activated Cdc42 can disrupt
      TJs, but neither a dominant-negative Cdc42 mutant nor the CRIB domain of gammaPAK
      (p21-activated kinase), which inhibits Cdc42 function, observably inhibit TJ
      formation. These results suggest that Cdc42 and Par6 negatively regulate TJ
      assembly in mammalian epithelial cells.

PMID- 11839276
TI  - The Drosophila standard brain.
AB  - Organisms and organs come in sizes and shapes. With size, science has no
      problems, but how to quantify shape? How similar are two birds or two brains?
      This problem is particularly pressing in cases like brains where structure
      reflects function. The problem is not new, but satisfying solutions have yet to
      be worked out. For brain anatomy, no general methodology for a statistically
      secured quantitative description is available. Using the small brain of the fly
      Drosophila melanogaster, we have explored a new approach combining
      immunohistochemistry, high-resolution 3D confocal microscopy, and advanced
      graphics computing. For a genetic model organism such as Drosophila, a
      quantitative assessment of brain structure is particularly rewarding, since it
      allows for the identification of genetic variants with subtle brain structure
      phenotypes and, even more importantly, the organization of the wealth of gene
      expression patterns in the brain into a genetic atlas linking molecular and
      organismic gene function. We now provide a representative standard for the brain
      of D. melanogaster wild-type with means and variances for several aspects of its
      shape. Its application to volumetry, mutants, and gene expression patterns is
      demonstrated.

PMID- 11839277
TI  - Vision modulates somatosensory cortical processing.
AB  - Over 150 years ago, E.H. Weber declared that experience showed that tactile
      acuity was not affected by viewing the stimulated body part. However, more recent
      investigations suggest that cross-modal links do exist between the senses.
      Viewing the stimulated body site improves performance on tactile discrimination
      and detection tasks and enhances tactile acuity. Here, we show that vision
      modulates somatosensory cortex activity, as measured by somatosensory event
      related potentials (ERPs). This modulation is greatest when tactile stimulation
      is task relevant. Visual modulation is not present in the P50 component
      reflecting the primary afferent input to the cortex but appears in the subsequent
      N80 component, which has also been localized to SI, the primary somatosensory
      cortex. Furthermore, we replicate previous findings that noninformative vision
      improves spatial acuity. These results are consistent with a hypothesis that
      vision modulates cortical processing of tactile stimuli via back projections from
      multimodal cortical areas. Several neurophysiological studies suggest that
      primary and secondary somatosensory cortex (SI and SII, respectively) activity
      can be modulated by spatial and tactile attention and by visual cues. To our
      knowledge, this is the first demonstration of direct modulation of somatosensory
      cortex activity by a noninformative view of the stimulated body site with
      concomitant enhancement of tactile acuity in normal subjects.

PMID- 11839278
TI  - Monocular vision leads to a dissociation between grip force and grip aperture
      scaling during reach-to-grasp movements.
AB  - It has been argued that visual perception and the visual control of action depend
      upon functionally distinct and anatomically separable brain systems.
      Electrophysiological evidence indicates that binocular vision may be particularly
      important for the visuomotor processing within the posterior parietal cortex, and
      neuropsychological and psychophysical studies confirm that binocular vision is
      crucial for the accurate planning and control of prehension movements. An
      unresolved issue concerns the consequences for visuomotor processing of removing
      binocular vision. By one account, monocular viewing leads to reliance upon
      pictorial visual cues to calibrate grasping and results in disruption to normal
      size-constancy mechanisms. This proposal is based on the finding that maximum
      grip apertures are reduced with monocular vision. By a second account, monocular
      viewing results in the loss of binocular visual cues and leads to strategic
      changes in visuomotor processing by way of altered safety margins. This proposal
      is based on the finding that maximum grip apertures are increased with monocular
      vision. We measured both grip aperture and grip force during prehension movements
      executed with binocular and monocular viewing. We demonstrate that each of the
      above accounts may be correct and can be observed within the same task.
      Specifically, we show that, while grip apertures increase with monocular vision,
      consistent with altered visuomotor safety margins, maximum grip force is
      nevertheless reduced, consistent with a misperception of object size. These
      results are related to differences in visual processing required for calibrating
      grip aperture and grip force during reaching.

PMID- 11839279
TI  - Essential role of type I(alpha) phosphatidylinositol 4-phosphate 5-kinase in
      neurite remodeling.
AB  - Rapid neurite remodeling is fundamental to nervous system development and
      plasticity and is regulated by Rho family GTPases that signal f-actin
      reorganization in response to various receptor ligands. Neuronal N1E-115 cells
      show dramatic neurite retraction and cell rounding in response to serum factors
      such as lysophosphatidic acid (LPA), sphingosine-1 phosphate (S1P), and thrombin,
      due to activation of the RhoA-Rho kinase pathway. Type I phosphatidylinositol 4
      phosphate 5-kinases (PIPkinase), which regulate cellular levels of
      PtdIns(4,5)P(2), have been suggested as targets of the RhoA-Rho kinase pathway
      able to modulate cytoskeletal dynamics. Here, we show that the introduction of
      Type Ialpha PIPkinase into N1E-115 cells leads to cell rounding and complete
      inhibition of neurite outgrowth, perhaps through the dissociation of vinculin and
      the destabilization of focal adhesions. This occurs independently of RhoA, Rho
      kinase, and the activation of actomyosin contraction. Strikingly, expression of
      kinase-dead PIPkinase promotes the outgrowth of neurites, which fail to retract
      in response to LPA, S1P, thrombin, or active RhoA. Moreover, neurite retraction
      in response to an endogenous neuronal guidance cue, Semaphorin3A, was also
      dependent on Type Ialpha PIPkinase. Our results suggest an essential role for a
      Type I PIPkinase during neurite retraction in response to a number of diverse
      stimuli.

PMID- 11839280
TI  - Histone H3 lysine 9 methylation occurs rapidly at the onset of random X
      chromosome inactivation.
AB  - In female mammals, a single X chromosome is stably and heritably silenced early
      in embryogenesis. The inactive X is characterized by asynchronous DNA replication
      and epigenetic chromatin modifications, including DNA methylation, histone H3/H4
      hypoacetylation, and incorporation of a variant histone macroH2A. X inactivation
      is initiated by a cis-acting RNA molecule, the X-inactive specific transcript
      (Xist), which coats the chromosome. However, the mechanism by which Xist induces
      chromosome silencing is poorly understood. An important approach towards
      answering this question has been to determine the temporal order of epigenetic
      chromatin modifications in an in vitro model system, differentiating XX embryonic
      stem (ES) cells, and thereby to identify candidate targets for Xist RNA. To date,
      these studies have demonstrated that, following accumulation of Xist RNA, the
      transition to late replication of the X chromosome is the earliest detectable
      event. H4 hypoacetylation, macroH2A1.2 incorporation, and DNA methylation all
      occur subsequently. Recently, it has been shown that chromatin of the inactive X
      is also characterized by methylation of histone H3 at lysine 9 (H3-K9). Here we
      show that H3-K9 methylation is a very early event in the process of X
      inactivation, which closely parallels the onset of Xist RNA accumulation.

PMID- 11839281
TI  - Dolly clouds cloning hopes.

PMID- 11839282
TI  - Keeping focus on the science. Interview by Nigel Williams.

PMID- 11839284
TI  - RNA silencing.

PMID- 11839285
TI  - Parental RNAi in Tribolium (Coleoptera).

PMID- 11839286
TI  - The lambda switch: cI closes the gap in autoregulation.
AB  - The bacteriophage lambda genetic switch is still yielding surprises. A recent
      study reveals that a long-range interaction involving proteins bound 2.4
      kilobases away from one another on the phage genome mediates negative
      autoregulation, solving a long-standing puzzle concerning the regulation of
      lysogeny.

PMID- 11839287
TI  - Developmental biology: regulation by selective gene localization.
AB  - Recent studies have shown that, early during sporulation in Bacillus subtilis,
      the temporary exclusion of 70% of the chromosome from the forespore compartment
      is critical to the regulated activation of two major transcription factors,
      sigma(F) and sigma(E).

PMID- 11839288
TI  - Stereopsis: where depth is seen.
AB  - Disparity-selective cells appear to occur in all parts of the visual cortex, but
      a recent fMRI study finds that some cortical areas are more strongly associated
      with disparity than others. More sophisticated tests of binocular function may be
      needed to identify the properties of single neurons that support this
      specialization.

PMID- 11839289
TI  - DNA packaging: a new class of molecular motors.
AB  - DNA is packaged into preformed bacteriophage capsids to liquid crystalline
      density by the action of a portal protein complex. Single molecule packaging
      studies indicate that this is a new and extremely powerful class of molecular
      motors.

PMID- 11839290
TI  - T-cell differentiation: MHC class I's sweet tooth lost on maturity.
AB  - The addition of sialic acid to O-linked glycans of the T-cell co-receptor CD8 is
      regulated during thymocyte differentiation. Two recent papers have shown that
      this glycosylation changes the avidity of the interaction between CD8 and MHC
      class I proteins, potentially altering signalling thresholds in thymocyte
      differentiation.

PMID- 11839291
TI  - Drosophila development: novel signal elicits visceral response.
AB  - A Drosophila screen aimed at furthering understanding of how tissues develop from
      the mesoderm has identified a novel signalling molecule that is proposed to
      signal from somatic muscle progenitors to direct the development of adjacent
      visceral muscle.

PMID- 11839292
TI  - Checkpoints: how to flag up double-strand breaks.
AB  - How checkpoint pathways recognise double-strand breaks has long been a mystery.
      Recent studies have found that two distinct checkpoint protein complexes
      associate independently with chromatin at the sites of DNA damage. Why do two
      distinct mechanisms recognise strand lesions, and what does this tell us about
      the checkpoint pathways?

PMID- 11839293
TI  - Epigenetics: monoallelic expression in the immune system.
AB  - Epigenetic modifications to DNA and chromatin programme important genome
      functions including gene expression, chromosomal architecture and stability, and
      the maintenance of developmental states. Recent findings further implicate
      epigenetic modifications in the control of allelic choice in the immune system.

PMID- 11839294
TI  - Turning clustering loops: sex determination in Caenorhabditis elegans.
AB  - The nematode Caenorhabditis elegans has two sexes: males and hermaphrodites.
      Hermaphrodites are essentially female animals that produce sperm and oocytes. In
      the past few years tremendous progress has been made towards understanding how
      sexual identity is controlled in the worm. These analyses have revealed that the
      regulatory pathway controlling sexual development is far from linear and that it
      contains a number of loops and branches that play crucial roles in regulating
      sexual development. This review summarizes our current understanding of the
      mechanisms that regulate sexual cell fate in C. elegans.

PMID- 11839295
TI  - Cytosines do it, thymines do it, even pseudouridines do it--base flipping by an
      enzyme that acts on RNA.
AB  - In the December 28, 2001 issue of Cell, Hoang and Ferre-D'Amare report the
      structure of a tRNA pseudouridine synthase, showing the target uridine flipped
      out from the tRNA and confirming that base flipping is not limited to enzymes
      that act on DNA.

PMID- 11839296
TI  - Rotavirus translation control protein takes RNA to heart.
AB  - Viruses commonly evolve distinct mechanisms to perform some of the same functions
      as cells. In the January 11 issue of Cell, Deo et al. describe the structure of
      rotavirus nonstructural protein 3 in complex with RNA, which explains how it acts
      as a functional homolog of cellular poly(A) binding protein to promote
      translation of the nonpolyadenylated rotavirus mRNAs.

PMID- 11839297
TI  - Turning on the Arp2/3 complex at atomic resolution.
AB  - The recently published 2 A X-ray crystal structure of bovine Arp2/3 complex gives
      us atomic scale insight into Arp2/3-mediated actin nucleation, while cryo-EM work
      and functional studies begin to fill in exciting mechanistic details.

PMID- 11839298
TI  - Structural biology: alive and skiing.
AB  - Structural biologists of all shapes and sizes gathered recently in Breckenridge,
      Colorado to discuss recent developments in the field. If we are to believe what
      they said, the future of structural biology is very bright.

PMID- 11839300
TI  - Small-scale batch crystallization of proteins revisited: an underutilized way to
      grow large protein crystals.
AB  - Growth of high-quality crystals is a major obstacle in many structural
      investigations. In recent years, the techniques for screening crystals have
      improved dramatically, whereas the methods for obtaining large crystals have
      progressed more slowly. This is an important issue since, although many
      structures can be solved from small crystals with synchrotron radiation, it is
      far easier to solve and refine structures when strong data is recorded from large
      crystals. In an effort to improve the size of crystals, a strategy for a small
      scale batch method has been developed that in many cases yields far larger
      crystals than attainable by vapor diffusion.

PMID- 11839301
TI  - Evidence of intradomain and interdomain flexibility in an OmpR/PhoB homolog from
      Thermotoga maritima.
AB  - Two-component systems, the predominant signal transduction strategy used by
      prokaryotes, involve phosphorelay from a sensor histidine kinase (HK) to an
      intracellular response regulator protein (RR) that typically acts as a
      transcription regulator. RRs are modular proteins, usually composed of a
      conserved regulatory domain, which functions as a phosphorylation-activated
      switch, and an attached DNA binding effector domain. The crystal structure of a
      Thermotoga maritima transcription factor, DrrD, has been determined at 1.5 A
      resolution, providing the first structural information for a full-length member
      of the OmpR/PhoB subfamily of RRs. A small interdomain interface occurs between
      alpha 5 of the regulatory domain and an antiparallel sheet of the effector
      domain. The lack of an extensive interface in the unphosphorylated protein
      distinguishes DrrD from other structurally characterized multidomain RRs and
      suggests a different mode of interdomain regulation.

PMID- 11839302
TI  - Insight into Schmid metaphyseal chondrodysplasia from the crystal structure of
      the collagen X NC1 domain trimer.
AB  - Collagen X is expressed specifically in the growth plate of long bones. Its C1q
      like C-terminal NC1 domain forms a stable homotrimer and is crucial for collagen
      X assembly. Mutations in the NC1 domain cause Schmid metaphyseal chondrodysplasia
      (SMCD). The crystal structure at 2.0 A resolution of the human collagen X NC1
      domain reveals an intimate trimeric assembly strengthened by a buried cluster of
      calcium ions. Three strips of exposed aromatic residues on the surface of NC1
      trimer are likely to be involved in the supramolecular assembly of collagen X.
      Most internal SMCD mutations probably prevent protein folding, whereas mutations
      of surface residues may affect the collagen X suprastructure in a dominant
      negative manner.

PMID- 11839303
TI  - Continuum secondary structure captures protein flexibility.
AB  - The DSSP program assigns protein secondary structure to one of eight states. This
      discrete assignment cannot describe the continuum of thermal fluctuations. Hence,
      a continuous assignment is proposed. Technically, the continuum results from
      averaging over ten discrete DSSP assignments with different hydrogen bond
      thresholds. The final continuous assignment for a single NMR model successfully
      reflected the structural variations observed between all NMR models in the
      ensemble. The structural variations between NMR models were verified to correlate
      with thermal motion; these variations were captured by the continuous
      assignments. Because the continuous assignment reproduces the structural
      variation between many NMR models from one single model, functionally important
      variation can be extracted from a single X-ray structure. Thus, continuous
      assignments of secondary structure may affect future protein structure analysis,
      comparison, and prediction.

PMID- 11839304
TI  - Structural evidence for ammonia tunneling across the (beta alpha)(8) barrel of
      the imidazole glycerol phosphate synthase bienzyme complex.
AB  - Since reactive ammonia is not available under physiological conditions, glutamine
      is used as a source for the incorporation of nitrogen in a number of metabolic
      pathway intermediates. The heterodimeric ImGP synthase that links histidine and
      purine biosynthesis belongs to the family of glutamine amidotransferases in which
      the glutaminase activity is coupled with a subsequent synthase activity specific
      for each member of the enzyme family. Its X-ray structure from the
      hyperthermophile Thermotoga maritima shows that the glutaminase subunit is
      associated with the N-terminal face of the (beta alpha)(8) barrel cyclase
      subunit. The complex reveals a putative tunnel for the transfer of ammonia over a
      distance of 25 A. Although ammonia tunneling has been reported for glutamine
      amidotransferases, the ImGP synthase has evolved a novel mechanism, which extends
      the known functional properties of the versatile (beta alpha)(8) barrel fold.

PMID- 11839305
TI  - Crystal structure of MJ1247 protein from M. jannaschii at 2.0 A resolution infers
      a molecular function of 3-hexulose-6-phosphate isomerase.
AB  - The crystal structure of the hypothetical protein MJ1247 from Methanococccus
      jannaschii at 2 A resolution, a detailed sequence analysis, and biochemical
      assays infer its molecular function to be 3-hexulose-6-phosphate isomerase (PHI).
      In the dissimilatory ribulose monophosphate (RuMP) cycle, ribulose-5-phosphate is
      coupled to formaldehyde by the 3-hexulose-6-phosphate synthase (HPS), yielding
      hexulose-6-phosphate, which is then isomerized to fructose-6-phosphate by the
      enzyme 3-hexulose-6-phosphate isomerase. MJ1247 is an alpha/beta structure
      consisting of a five-stranded parallel beta sheet flanked on both sides by alpha
      helices, forming a three-layered alpha-beta-alpha sandwich. The fold represents
      the nucleotide binding motif of a flavodoxin type. MJ1247 is a tetramer in the
      crystal and in solution and each monomer has a folding similar to the isomerase
      domain of glucosamine-6-phosphate synthase (GlmS).

PMID- 11839306
TI  - The structure of Ap(4)A hydrolase complexed with ATP-MgF(x) reveals the basis of
      substrate binding.
AB  - Ap(4)A hydrolases are Nudix enzymes that regulate intracellular dinucleoside
      polyphosphate concentrations, implicating them in a range of biological events,
      including heat shock and metabolic stress. We have demonstrated that ATP x MgF(x)
      can be used to mimic substrates in the binding site of Ap(4)A hydrolase from
      Lupinus angustifolius and that, unlike previous substrate analogs, it is in slow
      exchange with the enzyme. The three-dimensional structure of the enzyme complexed
      with ATP x MgF(x) was solved and shows significant conformational changes. The
      substrate binding site of L. angustifolius Ap(4)A hydrolase differs markedly from
      the two previously published Nudix enzymes, ADP-ribose pyrophosphatase and MutT,
      despite their common fold and the conservation of active site residues. The
      majority of residues involved in substrate binding are conserved in asymmetrical
      Ap(4)A hydrolases from pathogenic bacteria, but are absent in their human
      counterparts, suggesting that it might be possible to generate compounds that
      target bacterial, but not human, Ap(4)A hydrolases.

PMID- 11839307
TI  - Crystal structure of a novel carboxypeptidase from the hyperthermophilic archaeon
      Pyrococcus furiosus.
AB  - The structure of Pyrococcus furiosus carboxypeptidase (PfuCP) has been determined
      to 2.2 A resolution using multiwavelength anomalous diffraction (MAD) methods.
      PfuCP represents the first structure of the new M32 family of carboxypeptidases.
      The overall structure is comprised of a homodimer. Each subunit is mostly helical
      with its most pronounced feature being a deep substrate binding groove. The
      active site lies at the bottom of this groove and contains an HEXXH motif that
      coordinates the metal ion required for catalysis. Surprisingly, the structure is
      similar to the recently reported rat neurolysin. Comparison of these structures
      as well as sequence analyses with other homologous proteins reveal several
      conserved residues. The roles for these conserved residues in the catalytic
      mechanism are inferred based on modeling and their location.

PMID- 11839308
TI  - Crystal structure of 4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate kinase
      from Salmonella typhimurium at 2.3 A resolution.
AB  - The crystal structures of Salmonella typhimurium 4-amino-5-hydroxymethyl-2
      methylpyrimidine phosphate kinase (HMPP kinase) and its complex with substrate
      HMP have been determined. HMPP kinase catalyzes two separate ATP-dependent
      phosphorylation reactions and is an essential enzyme in the thiamin biosynthetic
      pathway. HMPP kinase is a homodimer with one active site per monomer and is
      structurally homologous to members of the ribokinase family. A comparison of the
      structure of HMPP kinase with other members of the ribokinase family suggests an
      evolutionary progression. Modeling studies suggest that HMPP kinase catalyzes
      both of its phosphorylation reactions using in-line displacement mechanisms. We
      propose that the active site accommodates the two separate reactions by providing
      two different binding modes for the phosphate group of HMP phosphate.

PMID- 11839309
TI  - The crystal structure of human tyrosyl-DNA phosphodiesterase, Tdp1.
AB  - Tyrosyl-DNA phosphodiesterase (Tdp1) catalyzes the hydrolysis of a phosphodiester
      bond between a tyrosine residue and a DNA 3' phosphate. The enzyme appears to be
      responsible for repairing the unique protein-DNA linkage that occurs when
      eukaryotic topoisomerase I becomes stalled on the DNA in the cell. The 1.69 A
      crystal structure reveals that human Tdp1 is a monomer composed of two similar
      domains that are related by a pseudo-2-fold axis of symmetry. Each domain
      contributes conserved histidine, lysine, and asparagine residues to form a single
      active site. The structure of Tdp1 confirms that the protein has many
      similarities to the members of the phospholipase D (PLD) superfamily and
      indicates a similar catalytic mechanism. The structure also suggests how the
      unusual protein-DNA substrate binds and provides insights about the nature of the
      substrate in vivo.

PMID- 11839310
TI  - Solution structure of the calponin CH domain and fitting to the 3D-helical
      reconstruction of F-actin:calponin.
AB  - Calponin is involved in the regulation of contractility and organization of the
      actin cytoskeleton in smooth muscle cells. It is the archetypal member of the
      calponin homology (CH) domain family of actin binding proteins that includes
      cytoskeletal linkers such as alpha-actinin, spectrin, and dystrophin, and
      regulatory proteins including VAV, IQGAP, and calponin. We have determined the
      first structure of a CH domain from a single CH domain-containing protein, that
      of calponin, and have fitted the NMR-derived coordinates to the 3D-helical
      reconstruction of the F-actin:calponin complex using cryo-electron microscopy.
      The tertiary fold of this single CH domain is typical of, yet significantly
      different from, those of the CH domains that occur in tandem pairs to form high
      affinity ABDs in other proteins. We thus provide a structural insight into the
      mode of interaction between F-actin and CH domain-containing proteins.

PMID- 11839311
TI  - Crystal structure of the copper-containing quercetin 2,3-dioxygenase from
      Aspergillus japonicus.
AB  - Quercetin 2,3-dioxygenase is a copper-containing enzyme that catalyzes the
      insertion of molecular oxygen into polyphenolic flavonols. Dioxygenation
      catalyzed by iron-containing enzymes has been studied extensively, but
      dioxygenases employing other metal cofactors are poorly understood. We determined
      the crystal structure of quercetin 2,3-dioxygenase at 1.6 A resolution. The
      enzyme forms homodimers, which are stabilized by an N-linked heptasaccharide at
      the dimer interface. The mononuclear type 2 copper center displays two distinct
      geometries: a distorted tetrahedral coordination, formed by His66, His68, His112,
      and a water molecule, and a distorted trigonal bipyramidal environment, which
      additionally comprises Glu73. Manual docking of the substrate quercetin into the
      active site showed that the different geometries of the copper site might be of
      catalytic importance.

PMID- 11839312
TI  - Crystal structure of PMM/PGM: an enzyme in the biosynthetic pathway of P.
      aeruginosa virulence factors.
AB  - The enzyme phosphomannomutase/phosphoglucomutase (PMM/PGM) from P. aeruginosa is
      required for the biosynthesis of two bacterial exopolysaccharides: alginate and
      lipopolysaccharide (LPS). Both of these molecules play a role in the virulence of
      P. aeruginosa, an important human pathogen known for its ability to develop
      antibiotic resistance and cause chronic lung infections in cystic fibrosis
      patients. The crystal structure of PMM/PGM shows that the enzyme has four
      domains, three of which have a similar three-dimensional fold. Residues from all
      four domains of the protein contribute to the formation of a large active site
      cleft in the center of the molecule. Detailed information on the active site of
      PMM/PGM lays the foundation for structure-based inhibitor design. Inhibitors of
      sufficient potency and specificity should impair the biosynthesis of alginate and
      LPS, and may facilitate clearance of the bacteria by the host immune system and
      increase the efficacy of conventional antibiotic treatment against chronic P.
      aeruginosa infections.

PMID- 11839313
TI  - Professional liability, patient safety, and first do no harm.

PMID- 11839315
TI  - Past, present, and future of pancreatic surgery.
AB  - The advances in the surgical treatment of pancreatic disease in the 20th century
      were built on careful anatomic and physiologic studies dating to the early 1800s.
      Operations for neoplastic diseases developed in the 1930s by Whipple, Trimble,
      and others allowed pancreatic malignancies to be removed with ever increasing
      safety. Endocrine tumors of the pancreas were described and treated surgically.
      Patients with pancreatitis now have a number of surgical alternatives available
      for their individual circumstances. The future of surgery for pancreatic disease
      lies in the results of the human genome project and the fields of genomics and
      proteomics that resulted. The rapidity with which knowledge of gene expression is
      advancing owing to new technologies such as the microarray biochip is amazing.
      The future of pancreatic surgery is bright.

PMID- 11839314
TI  - The abdominal compartment syndrome is a morbid complication of postinjury damage
      control surgery.
AB  - BACKGROUND: The abdominal compartment syndrome (ACS) is a recognized complication
      of damage control surgery (DCS). The purposes of this study were to (1) determine
      the effect of ACS on outcome after DCS, (2) identify patients at high risk for
      the development of ACS, and (3) determine whether ACS can be prevented by
      preemptive intravenous bag closure during DCS. METHODS: Patients requiring
      postinjury DCS at our institution from January 1996 to June 2000 were divided
      into groups depending on whether or not they developed ACS. ACS was defined as an
      intra-abdominal pressure (IAP) greater than 20 mm Hg in association with
      increased airway pressure or impaired renal function. RESULTS: ACS developed in
      36% of the 77 patients who underwent DCS with a mean IAP prior to decompression
      of 26 +/- 1 mm Hg. The ACS versus non-ACS groups were not significantly different
      in patient demographics, Injury Severity Score, emergency department vital signs,
      or intensive care unit admission indices (blood pressure, temperature, base
      deficit, cardiac index, lactate, international normalized ratio, partial
      thromboplastin time, and 24-hour fluid). The initial peak airway pressure after
      DCS was higher in those patients who went on to develop ACS. The development of
      ACS after DCS was associated with increased ICU stays, days of ventilation,
      complications, multiorgan failure, and mortality. CONCLUSIONS: ACS after
      postinjury DCS worsens outcome. With the exception of early elevation in peak
      airway pressure, we could not identify patients at higher risk for ACS; moreover,
      preemptive abdominal bag closure during initial DCS did not prevent this highly
      morbid complication.

PMID- 11839317
TI  - Inflammation.

PMID- 11839316
TI  - Radiofrequency ablation for unresectable hepatic tumors.
AB  - BACKGROUND: Radiofrequency ablation (RFA) is a relatively new treatment for
      unresectable hepatic tumors. The purpose of this analysis was to examine the
      frequency of complications and local recurrence associated with RFA. METHODS:
      Patients who underwent RFA of hepatic tumors with curative intent were included
      in this study. At laparotomy, RFA was performed using intraoperative ultrasound
      guidance. Computed tomography scans were obtained in the immediate postoperative
      period and every 3 to 6 months thereafter. RESULTS: Forty patients underwent RFA
      for 122 hepatic tumors. Thirty-one patients had metastatic lesions from
      colorectal cancer; 9 had other liver tumors. Complications occurred in 8
      patients. With 9.5 months median follow-up, 6 patients had local recurrence of
      their ablated tumors. CONCLUSIONS: Our initial experience shows that RFA can
      effectively eradicate unresectable hepatic tumors. The rate and severity of
      complications appear acceptable. However, further study is necessary to assess
      long-term recurrence rates and effect on overall survival.

PMID- 11839318
TI  - Burn center management of necrotizing soft-tissue surgical infections in unburned
      patients.
AB  - BACKGROUND: Patients with necrotizing soft-tissue infections present great
      challenges in management from initial presentation through definitive care.
      Because burn centers concentrate expertise in critical care, wound management,
      and rehabilitation, we examined the effectiveness of burn center care for
      patients with necrotizing infections. METHODS: We reviewed our burn center's
      experience with all patients admitted from 1990 through 1999 with a primary
      diagnosis of necrotizing fasciitis (NF) or Fournier's gangrene (FG). RESULTS:
      Fifty-seven patients were identified, 18 with FG and 39 with NF. Patients had a
      high incidence of preexisting medical problems, including diabetes (37%), obesity
      defined as greater than 20% above ideal body weight (33%), and hypertension
      (33%). Seven of 57 (12%) patients died. Patients required a mean of 4.1 operative
      procedures (range 1 to 15) for definitive wound closure. The mean length of stay
      (survivors only) was 28.5 days, (range 3 to 70). Although costs increased
      throughout this period, a formal program of cost-containment resulted in no
      increase in actual charges per day, from a mean of $4,735 in 1991 to $5,202 in
      1999. CONCLUSIONS: Burn centers can provide successful and cost-effective acute
      care, definitive wound closure, and rehabilitation for patients with NF and FG.

PMID- 11839319
TI  - Thoracic epidural versus patient-controlled analgesia in elective bowel
      resections.
AB  - BACKGROUND: This study was undertaken to determine if thoracic epidural analgesia
      is of practical benefit after bowel resection. METHODS: Patients were
      prospectively randomized to receive either a thoracic epidural or patient
      controlled analgesia for pain control after bowel resection. A standardized
      postoperative protocol was instituted after surgery. RESULTS: Pain scores were
      significantly lower in the epidural group. Return of bowel function, and interval
      to discharge was not different between groups. Cost and complication rates were
      significantly higher in the epidural group. CONCLUSIONS: Although pain scores
      were significantly lower in the epidural group, this did not translate into a
      quicker return of bowel function or earlier discharge of the patient.
      Furthermore, the epidural group had a significantly higher complication rate and
      cost. Therefore, while thoracic epidural analgesia provides superior pain
      control, it does not offer a significant advantage over patient-controlled
      analgesia in return of bowel function after bowel resection.

PMID- 11839320
TI  - Improved patency of infrainguinal polytetrafluoroethylene bypass grafts using a
      distal Taylor vein patch.
AB  - OBJECTIVE: The purpose of this study was to evaluate graft patency and limb
      salvage rates for infrainguinal polytetrafluoroethylene (PTFE) bypass grafts
      using distal anastomotic Taylor vein patch in patients lacking suitable vein
      conduit. METHODS: We reviewed 44 patients who underwent infrainguinal bypass
      between January 1996 and August 2000 using 6-mm PTFE and a distal Taylor vein
      patch. Postoperative oral anticoagulation was administered to 80% of patients.
      Graft patency was confirmed during follow-up with serial graft duplex scanning.
      RESULTS: Operative indications were rest pain, nonhealing ulcer, or gangrene in
      76% of patients, 43% of whom had undergone previous ipsilateral leg bypass.
      Distal anastomotic sites were the below-knee popliteal (29%) and tibial-peroneal
      arteries (67%). At 1 month, 1 year, and 2 years, respectively, the primary
      patencies (SE <10%) were 86%, 71%, and 71%; limb salvage rates were 95%, 75%, and
      66%; and mortality rates were 5%, 20%, and 20%. CONCLUSIONS: These early results
      with PTFE and distal Taylor vein patch are promising, and markedly superior to
      previous reports of PTFE without anastomotic modification. Further long-term
      follow-up will be necessary to determine the 3- to 5-year durability of such
      reconstructions.

PMID- 11839321
TI  - Intraoperative localization after stereotactic breast biopsy without a needle.
AB  - BACKGROUND: Needle localization breast biopsy (NLBB) is the standard for the
      removal of breast lesions after vacuum-assisted breast biopsy (VABB).
      Disadvantages include a miss rate of 0% to 22%, risk of vasovagal reactions, and
      scheduling difficulties. We hypothesized that the hematoma resulting from VABB
      could be used to localize the VABB site with intraoperative ultrasonography (US)
      for excision. METHODS: Twenty patients had VABB followed by intraoperative US
      guided excision. RESULTS: The previous VABB site in 19 patients was successfully
      visualized with intraoperative US and excised at surgery. One patient had
      successful removal of the targeted area under US guidance, but failed to show
      removal of the clip on initial specimen mammogram. CONCLUSION: This study
      demonstrates the effectiveness of US in identifying hematomas after VABB for
      excision. This technique, which can be performed weeks after VABB, improves
      patient comfort and allows easier scheduling.

PMID- 11839322
TI  - The clinical behavior of desmoplastic melanoma.
AB  - BACKGROUND: Desmoplastic melanoma (DM) is a rare variant of malignant melanoma. A
      better understanding of the clinical course of DM will impact on its treatment.
      METHODS: We reviewed the medical records of 59 patients with DM seen at the Mayo
      Clinics Scottsdale and Rochester since 1985. RESULTS: Thirty-seven (63%) patients
      were male with a mean age of 62.8 years. The mean DM thickness was 6.5 mm. A
      total of 23 patients (39%) experienced local recurrence (LR). LR correlated with
      positive, unknown, or <1 cm margins. Fifty percent of patients who locally
      recurred subsequently developed metastatic disease. No patients were found to
      have positive nodal disease during ELND (16) or SLN biopsy (12). Only 1 patient
      (2%) developed delayed regional node metastases. Sixteen patients developed
      metastatic disease. The most common site was the lungs (81%). CONCLUSIONS: LR is
      a significant problem and correlates with an increased risk of systemic
      metastatic disease. With the rare occurrence of lymphatic spread, we recommend
      patients undergo SLN biopsy only. DM appears to preferentially metastasize to the
      lungs and should be targeted when evaluating the patient for metastatic disease.

PMID- 11839323
TI  - Is breast cancer in young Latinas a different disease?
AB  - BACKGROUND: Breast cancer appears to be more aggressive in young women (< or =35
      years). Race/ethnicity may further influence prognosis. The purpose of this
      review is to determine whether breast cancer in young Latinas differs from that
      in other women. METHODS: Our institutional (1977-2000) and state (1988-2000)
      tumor registries were reviewed and breast cancer cases analyzed. Data are
      expressed as mean +/- SEM. RESULTS: At our institution, 56 (7%) of 748 breast
      cancer patients were < or =35 years old; 32 (57%) were Latina. Compared with non
      Latinas, Latinas presented at a younger age (P <0.05) and had more stage III/IV
      disease (38% versus 29%; P >0.05) and bilaterality (22% versus 8%; P >0.05), and
      worse 5-year survival (63% versus 83%; P >0.05). Statewide data were consistent
      with our institutional data. CONCLUSIONS: Latinas comprise a disproportionate
      share of our young breast cancer population, and may suffer more aggressive
      disease than other young women. Young Latinas may benefit from more vigilant
      screening and should be considered for novel therapeutic protocols.

PMID- 11839324
TI  - Surgical conservation planning after neoadjuvant chemotherapy for stage II and
      operable stage III breast carcinoma.
AB  - BACKGROUND: This study was performed to investigate the extent of tumor
      downstaging achieved in women with operable breast cancer treated with
      neoadjuvant chemotherapy and breast-conservation surgery, develop recommendations
      for effective surgical planning, and report local-regional recurrence rates with
      this approach. METHODS: One hundred nine patients with stage II or III (T3N1)
      breast cancer were treated in three prospective trials utilizing four cycles of 5
      fluorouracil, doxorubicin, and cyclophosphamide (FAC, n = 72) or paclitaxel (n =
      37) followed by segmental resection (n = 109) and axillary node dissection (n =
      94). Postoperatively, patients received 4 additional cycles of FAC followed by
      irradiation of the breast. The median follow-up was 53 months. RESULTS: The
      median tumor size was 4 cm (range 1.1 to 9 cm) at presentation and only 1 cm
      (range 0 to 4.5 cm) after four cycles of chemotherapy. The primary tumor could
      not be palpated after chemotherapy in 55% of 104 patients presenting with a
      palpable mass and therefore required needle localization or ultrasound guidance
      for surgical resection. Of the 34 patients clinically deemed to have no residual
      carcinoma in the breast after chemotherapy and before surgery, only 50% of these
      patients were found to have no residual carcinoma on pathologic examination after
      surgery. Patients with primary tumors < or =2 cm were significantly more likely
      than patients with larger tumors to have complete eradication of the primary
      tumor prior to surgery (P <0.001). The 5-year local-regional recurrence rate was
      5%. CONCLUSIONS: Tumor downstaging is marked in patients with operable breast
      cancer and requires close monitoring during chemotherapy. We recommend placement
      of metallic tumor markers when the primary tumor is < or =2 cm to facilitate
      adequate resection and pathologic processing. Resection of the tumor bed remains
      necessary in women deemed to have a complete clinical response to ensure low
      rates of recurrence.

PMID- 11839325
TI  - Utility of intraoperative frozen section analysis of sentinel lymph nodes in
      breast cancer.
AB  - BACKGROUND: Intraoperative frozen section pathologic analysis of sentinel lymph
      node (SLN) may guide immediate (single-stage) completion axillary dissection for
      patients with nodal metastases. METHODS: The results of 203 consecutive patients
      undergoing SLN biopsy who had intraoperative pathology consultation between
      January 1998 and September 2000 were reviewed. SLN were analyzed by standard
      frozen section procedures. Final pathologic analysis included hematoxylin and
      eosin (H&E) staining of serial sections at 2-mm intervals. RESULTS: Frozen
      section analysis correctly identified a positive or negative result in 185 of 203
      cases (overall accuracy 91%). In 17 of 53 cases, the SLNs were negative for tumor
      by frozen section, but positive on permanent section analysis (sensitivity 68%).
      The mean size of the nodal metastases was 6.2 mm and 1.5 mm in patients found to
      have true positive and false negative results, respectively (P <0.003). A single
      false positive SLN is reported. CONCLUSIONS: Two thirds of the patients were
      spared the need for reoperative axillary lymphadenectomy.

PMID- 11839326
TI  - Comparison of postoperative outcomes in ulcerative colitis and familial polyposis
      patients after ileoanal pouch operations.
AB  - BACKGROUND: Pouchitis is a poorly understood inflammatory condition that occurs
      in the ileal pouches of patients who have undergone the ileal-pouch anal
      anastomosis after restorative proctocolectomy. This postoperative condition is
      much more common in patients with ulcerative colitis (UC) than familial
      adenomatous polyposis (FAP) colitis. It has been suggested that, owing to
      pouchitis, UC patients do not attain the same quality of life that FAP patients
      do after the ileal-pouch anal anastomosis operation. We hypothesized that health
      related quality of life does not differ between FAP and UC patients. METHODS: We
      analyzed the postoperative morbidity and gastrointestinal function in 110
      consecutive patients having undergone the ileal-pouch anal anastomosis for either
      UC or FAP at OU Medical Center from 1983 to 2000 by retrospective record review.
      Health-related quality of life was assessed in 83 patients using the Short
      Inflammatory Bowel Disease Questionnaire (SIBDQ) and the Medical Outcome Study
      Short-Form 36 (SF-36) questionnaire. RESULTS: With the exception of pouchitis,
      there was no difference in perioperative outcome, morbidity, or functional status
      between UC and FAP patients. The SIBDQ and SF-36 revealed no statistically
      significant difference between FAP and UC patients. CONCLUSIONS: As expected, UC
      patients are more likely to develop pouchitis. Despite this, our data reveal that
      both patient groups enjoy a similarly good functional status and quality of life.

PMID- 11839327
TI  - Early postoperative enteral feeding increases anastomotic strength in a
      peritonitis model.
AB  - BACKGROUND: Tumor necrosis factor alpha (TNF-alpha) has been shown to decrease
      collagen synthesis and increase collagenase activity leading to impaired wound
      healing. Our hypothesis was that immediate postoperative feeding would decrease
      TNF-alpha, therefore increasing anastomotic healing in a peritonitis model.
      METHODS: Twelve Sprague-Dawley rats underwent cecal ligation and puncture to
      induce peritonitis. Six hours after induction of peritonitis an ileocecectomy and
      ileocolostomy was performed. Group 1 animals (n = 6) had immediate access to food
      and water, whereas group 2 (n = 6) had free access to water only. At 48 hours,
      weight loss, nitrogen loss, anastamotic bursting strength (ABS), TNF-alpha,
      interleukin-6 (IL-6), and IL-10 were measured. RESULTS: Weight loss was similar
      in the two groups. Group 1 rats had a significantly lower mean TNF-alpha level
      (17.3 +/- 10 versus 17.3 +/- 10 mcg/Dl, P = 0.05). ABS was also significantly
      higher in group 1 rats when compared with group 2 rats (81 +/- 34 versus 39 +/-
      13 mm HG, P = 0.03). CONCLUSIONS: These data suggest that immediate postoperative
      feeding results in a beneficial change in the cytokine profile.

PMID- 11839328
TI  - Outcome of the antegrade colonic enema procedure in children with chronic
      constipation.
AB  - BACKGROUND: Chronic constipation and fecal incontinence in children related to
      pelvic trauma, congenital anomalies, or malignancy will eventually lead to
      significant social and psychologic stress. Maximal medical treatment (daily
      enemas and laxatives) can also be difficult to maintain in many children.
      METHODS: At our children's hospital, 11 children with chronic constipation or
      fecal incontinence or both underwent the antegrade colonic enema (ACE) procedure.
      The operation involved constructing a conduit into the cecum using either the
      appendix (n = 8) or a "pseudo-appendix" created from a cecal flap (n = 3). We
      report our surgical results. RESULTS: Mean child age was 9.6 (5 to 18) years.
      With a mean follow-up of 14 (6 to 24) months, 10 of the children (91%) had
      significant improvement and 7 children (64%) are completely clean with no soiling
      and controlled bowel movements after irrigation. CONCLUSIONS: Regular colonic
      lavage after the ACE procedure allows children with chronic constipation and
      fecal incontinence to regain normal bowel habits and a markedly improved
      lifestyle. This procedure should be considered before colostomy in children and
      adults for the treatment of fecal incontinence from a variety of causes.

PMID- 11839329
TI  - Vacuum-assisted wound closure provides early fascial reapproximation in trauma
      patients with open abdomens.
AB  - BACKGROUND: Damage control and decompressive laparotomies salvage severely
      injured patients who would have previously died. Unfortunately, many of these
      patients develop open abdomens. A variety of management strategies exist. The end
      result in many cases, however, is a large ventral hernia that requires a complex
      repair 6 to 12 months after discharge. We instituted vacuum-assisted wound
      closure (VAWC) to achieve early fascial closure and eliminate the need for
      delayed procedures. METHODS: For 12 months ending June 2000, 14 of 698 trauma
      intensive care unit admissions developed open abdomens and were managed with VAWC
      dressing. This was changed every 48 hours in the operating room with serial
      fascial approximation until complete closure. RESULTS: Fascial closure was
      achieved in 13 patients (92%) in 9.9 +/- 1.9 days, and 2.8 +/- 0.6 VAWC dressing
      changes were performed. There were 2 wound infections, no eviscerations, and no
      enteric fistulas. CONCLUSIONS: Use of VAWC can safely achieve early fascial
      closure in more than 90% of trauma patients with open abdomens.

PMID- 11839330
TI  - Results after colectomy for colonic inertia: a sixteen-year experience.
AB  - BACKGROUND: Colonic inertia (CI) is a disturbance of colonic motility
      characterized by severe constipation and abdominal pain. This study was conducted
      to assess the results of total abdominal colectomy (TAC) in the management of CI.
      METHODS: A retrospective chart review of 55 patients who underwent TAC for CI was
      conducted. RESULTS: Forty-eight patients (87%) were female with an average age of
      40; severe constipation existed 2 years prior to surgery. Symptoms included
      severe constipation (100%) and abdominal pain (84%); diagnostic workup included
      sitz marker study, anal manometry, and Gastrografin enema. In all cases, sitz
      marker studies were abnormal and anal manometry was normal. Histologically, no
      patient had absence of neuroenteric plexuses. Complications included prolonged
      ileus (24%) and small bowel obstruction (8%). Some 49 patients (89%) had "good"
      or "excellent" results and 6 patients (11%) had "poor" results. Postoperative
      stool frequency was 5, 4, and 3 per day at 1, 2, and 12 months, respectively.
      CONCLUSIONS: TAC results in resolution of constipation in most patients. We
      conclude that TAC is effective treatment in patients with CI.

PMID- 11839332
TI  - Can specific preoperative counseling increase the likelihood a woman will choose
      postmastectomy breast reconstruction?
AB  - BACKGROUND: Low reconstruction rates after mastectomy for breast cancer raise
      questions about the impact of preoperative education. This study determines
      whether counseling about reconstruction influences the decision about
      reconstruction. METHODS: The study was based on a prospectively collected
      database of breast cancer surgery. RESULTS: A total of 299 operations for breast
      cancer were performed. Of 127 mastectomies, 21 (16%) were not candidates. In all,
      106 women were specifically educated about reconstruction; 40 (37%) women
      consulted with a plastic surgeon; and 22 (21%) women ultimately chose
      reconstruction. Forty women had the option of mastectomy or breast conservation.
      Twelve (30%) women accepted a consultation with a plastic surgeon. Six of these
      women (15%) ultimately chose reconstruction. Mastectomy was required in 66 women;
      28 (42%) accepted a consultation with a plastic surgeon; 16 (24%) underwent
      reconstruction; 3 additional women are planning delayed reconstruction (28%).
      CONCLUSIONS: Reconstruction is more likely when mastectomy is required than when
      it is chosen. Low reconstruction rates reflect patient desire rather than access
      or education.

PMID- 11839331
TI  - Secondary abdominal compartment syndrome is a highly lethal event.
AB  - BACKGROUND: Recent reports have described resuscitation-induced, "secondary"
      abdominal compartment syndrome (ACS) in trauma patients without intra-abdominal
      injuries. We have diagnosed secondary ACS in a variety of nontrauma as well as
      trauma patients. The purpose of this review is to characterize patients who
      develop secondary ACS. METHODS: Our prospective ACS database was reviewed for
      cases of secondary ACS. Physiologic parameters and outcomes were recorded. Data
      are expressed as mean +/- SEM. RESULTS: Fourteen patients (13 male, aged 45 +/- 5
      years) developed ACS 11.6 +/- 2.2 hours following resuscitation from shock.
      Eleven (79%) had required vasopressors; the worst base deficit was 14.1 +/- 1.9.
      Resuscitation included 16.7 +/- 3.0 L crystalloid and 13.3 +/- 2.9 red blood cell
      units. Decompressive laparotomy improved intra-abdominal, systolic, and peak
      airway pressures, as well as urine output; however, mortality was 38% among
      trauma and 100% among nontrauma patients. CONCLUSIONS: Secondary ACS may be
      encountered by general surgeons in a variety of clinical scenarios; resuscitation
      from severe shock appears to be the critical factor. Early identification and
      abdominal decompression are essential. Unfortunately, in our experience, this is
      a highly lethal event.

PMID- 11839333
TI  - The influence of gender on complications of carotid endarterectomy.
AB  - PURPOSE: Carotid endarterectomy (CEA) effectively reduces stroke risk in properly
      selected patients. Subgroup analysis of the Asymptomatic Carotid Artery Study
      trial noted increased complications in women. Additional studies implicate female
      gender as a risk factor for perioperative stroke, leading some clinicians to
      modify the indications for CEA in women. The purpose of this study was to
      determine the influence of gender on the risk of perioperative complications in
      patients undergoing CEA. METHODS: The records of all patients who underwent CEA
      at a university medical center from January 1995 to December 1999 were reviewed.
      Patient demographics, procedure related risk factors, operative details, and
      specific complications were entered into a database for statistical analysis.
      RESULTS: A total of 324 consecutive patients underwent CEA during the study
      period. There were 199 men (61%) and 125 women (39%). Among the men and women,
      there were no differences in age, smoking, hypertension, hypercholesterolemia,
      diabetes, family history, renal insufficiency, or symptomatic versus asymptomatic
      indications for CEA. More women than men received a carotid patch (90.4% versus
      77.9%, P = 0.003). One woman died (0.8%) and no men died for a total combined 30
      day mortality of 0.31% (P = not significant). Men and women did not differ in
      rates of stroke (1.5% versus 2.4%) or perioperative myocardial infarction (1.0%
      versus 0.8%). In addition, there was no difference when stroke and death rates
      were combined (2% versus 3.2%). The length of stay (2.2 versus 2.6 days) was also
      not different. CONCLUSIONS: There are no significant differences in rate of
      stroke, myocardial infarction, or 30-day mortality, between men and women
      following CEA. Women should not be excluded from the benefits of CEA based on
      perceived increased complication rates.

PMID- 11839334
TI  - Infectious complications resulting from use of hemostatic puncture closure
      devices.
AB  - BACKGROUND: Femoral access site complications have increased as the fields of
      invasive cardiology, radiology, and endovascular surgery have emerged. In order
      to address one of these complications, hemorrhage, the hemostatic puncture
      closure devices were developed. METHODS: Retrospective review of cardiac
      catheterizations performed at a single institution to investigate infectious
      groin complications related to use of the Perclose Prostar and Techstar devices.
      RESULTS: Infectious groin complications were significantly higher in the Perclose
      group as compared with manual compression. Three patients had clinical and
      laboratory evidence of arterial infection whereas 2 had soft tissue infections.
      All 5 required operative intervention ranging from incision and drainage to
      arterial reconstruction. Hemorrhagic complications were not significantly
      different between the two groups. CONCLUSIONS: The Perclose devices provide
      hemostasis after femoral artery catheterization similar to manual compression.
      However, infectious groin complications appear to be more common with these
      devices.

PMID- 11839335
TI  - Is intraoperative cholangiography during laparoscopic cholecystectomy cost
      effective?
AB  - BACKGROUND: Common bile duct injuries occur in 0.2% to 0.8% of laparoscopic
      cholecystectomies (LC). Intraoperative cholangiograms (IOCG) are a useful means
      of detecting common bile duct injuries in the operating room. METHODS: Data were
      retrospectively reviewed for patients referred for management of common duct
      injuries from 1996 to 2000. Cost data were obtained from hospital records. Legal
      settlements were obtained from published sources. RESULTS: Twenty-one patients
      (0.133%) were found to have bile duct injuries and incurred median hospital stays
      of 11.5 days at an average cost of $587,491. The average cost of those requiring
      reoperation was $669,134. The 21 cases in our sample had total charges of
      $10,819,767. Performing IOCG during each LC in Orange County would have cost
      $10,669,725. If extrapolated to state and nationwide levels, the savings is far
      greater. CONCLUSIONS: IOCG during LC is a cost-effective means of preventing the
      costs of delayed recognition of bile duct injuries.

PMID- 11839336
TI  - Skin only or silo closure in the critically ill patient with an open abdomen.
AB  - BACKGROUND: The morbidity and mortality of various open abdominal techniques
      remains unclear. METHODS: A retrospective review was made of all trauma or
      general surgery patients who underwent an open abdominal closure from January
      1997 to December 2000, at a large urban acute care hospital. Data are mean +/-
      SD. RESULTS: From 1997 to 2000, 181 patients (aged 39.8 +/- 16.5 years) had an
      open abdomen for abdominal infection, planned reexploration, abdominal
      compartment syndrome, inability to reapproximate fascia, or as part of a "damage
      control" procedure. Twenty-three patients went on to develop an abdominal
      compartment syndrome. Gastrointestinal fistulas occurred in 26 patients, and 9
      patients had a dehiscence. The overall mortality was 44.7%. Of the survivors, 52%
      went on to fascial closure, requiring 1 to 7 additional abdominal operations.
      CONCLUSIONS: The morbidity of the open abdomen varies with the particular
      indication. Gastrointestinal fistulas are the most common acute complication and
      an abdominal wall hernia, the most common chronic complication.

PMID- 11839337
TI  - Gastric pacing is a new surgical treatment for gastroparesis.
AB  - BACKGROUND: Gastroparesis is a chronic gastric motility disorder affecting mostly
      young and middle-aged women who present with nausea, abdominal pain, early
      satiety, vomiting, fullness, and bloating. METHODS: From April 1998 to September
      2000, 25 patients underwent gastric pacemaker placement. All had documented
      delayed gastric emptying by a radionucleotide study. Nineteen patients had
      diabetic gastroparesis, 3 had developed postsurgical gastroparesis, and 3 had
      idiopathic gastroparesis. Baseline and postoperative follow-ups were done by a
      self-administered questionnaire on which the patients rated the severity and
      frequency of nausea and vomiting. Gastric emptying times were also followed up
      using a radionucleotide technique. RESULTS: Both the severity and frequency of
      nausea and vomiting improved significantly at 3 months and was sustained for 12
      months. Gastric emptying time was also numerically faster over the 12-month
      period. Three of the devices have been removed. One patient died of causes
      unrelated to the pacemaker 10 months postoperatively. CONCLUSIONS: After
      placement of the gastric pacemaker, patients rated significantly fewer symptoms
      and had a modest acceleration of gastric emptying.

PMID- 11839338
TI  - Prophylactic antibiotics are not indicated in clean general surgery cases.
AB  - BACKGROUND: In assigning risk of infection, the traditional wound classification
      system has been replaced by the National Nosocomial Infection Surveillance (NNIS)
      system. NNIS classification is determined by procedure length, wound cleanliness,
      and ASA status. To date, no prophylactic antibiotic guidelines have been proposed
      for the NNIS system. METHODS: Clean general surgery cases were retrospectively
      reviewed in our hospital for infection and prophylactic antibiotic use. These
      cases were then stratified per the NNIS system. RESULTS: One thousand twenty
      three clean general surgery cases had 16 (1%) surgical site infections. The
      infection rate in NNIS class 0, 1, and 2 cases not given prophylactic antibiotics
      was 1.21%, 3.03%, and 0%, respectively. The infection rate in NNIS class 0, 1,
      and 2 cases given prophylactic antibiotics was 0.94%, 2.44%, and 6.67%,
      respectively. CONCLUSIONS: No statistically significant decrease in infection
      rate was demonstrated by us using prophylactic antibiotics, regardless of the
      NNIS classification in clean general surgery cases.

PMID- 11839339
TI  - Deriving the indications for laparoscopic appendectomy from a comparison of the
      outcomes of laparoscopic and open appendectomy.
AB  - BACKGROUND: Indications for laparoscopic appendectomy (LA) remain controversial
      and poorly defined. We sought to identify indications for LA through a comparison
      of LA and open appendectomies (OA). METHODS: We reviewed demographics, coexisting
      medical conditions, radiology and pathology data, hospital course, and
      complications from charts on all LA patients and a comparison group of OA done
      from 1991 to 1998. RESULTS: The following were significantly associated with LA:
      female sex, higher mean body mass index (BMI), coexisting medical problems,
      private insurance, and daytime surgery. The OA group was significantly more
      likely to have: a radiology report suggesting the diagnosis of acute
      appendicitis, perforation of the appendix, intensive care unit admission, and
      complications in their hospital course. Forty-one percent of the LA patients did
      not have appendicitis, compared with 20% of the OA patients. CONCLUSIONS: Daytime
      surgery, women, private insurance, coexisting medical problems, prior abdominal
      surgery, higher BMI, and less severe disease appear to be used by surgeons as
      indicators for LA. The threshold for surgical exploration appears to be lower for
      LA.

PMID- 11839340
TI  - Laparoscopic exploration for the clinically undetected hernia in infancy and
      childhood.
AB  - BACKGROUND: Routine contralateral groin exploration in infants and children with
      a clinically detected inguinal hernia is the subject of much debate. The
      detection of a patent processus vaginalis by transinguinal laparoscopy has proven
      advantageous. However, controversy remains regarding the true incidence of a
      contralateral patent processus vaginalis as well as which of these will actually
      develop into a clinically apparent hernia. METHODS: From January 1997 through
      December 1999, 358 infants and children (aged 1 to 157 months, mean 32) were
      treated in the three University of Oklahoma teaching hospitals in Tulsa,
      Oklahoma, for inguinal hernia. The findings at laparoscopic exploration of the
      contralateral side were recorded to determine the incidence of contralateral
      patency as it relates to a child's age, gender, and side of the initial clinical
      diagnosis. RESULTS: The overall incidence of a patent processus vaginalis on
      contralateral examination was 33% (117 of 358). All patent processus vaginalis
      were repaired. Bilateral inguinal hernia was significantly more common in younger
      patients (present in 50% if less than 1 year, 45% if less than 2 years, 37% if
      less than 5 years, and 15% if greater than 5 years of age; P <0.05). In boys, the
      incidence was 49%, 45%, and 32% in those under 1 year of age, under 2 years of
      age, and in total, respectively. In girls, the incidence was 59%, 50%, and 37% in
      those under 1 year of age, under 2 years of age, and in total, respectively. The
      side of the clinically detected hernia did not influence the laparoscopic
      findings of a contralateral hernia with 30% (50 of 169) positive findings on left
      inguinal exploration versus 31% (28 of 90) positive findings on right inguinal
      exploration. CONCLUSIONS: The high incidence of a contralateral patent processus
      vaginalis warrants routine laparoscopic exploration in infants and children
      undergoing unilateral inguinal hernia repair, especially those less than 5 years
      of age. The use of transinguinal laparoscopic explorations avoids unnecessary
      open exploration in 66% of infants and children undergoing inguinal hernia
      repair.

PMID- 11839341
TI  - Endoscopic prosthesis augmentation of the lower esophageal sphincter in swine.
AB  - HYPOTHESIS: Endoscopically delivered prostheses are safe, durable, and may
      augment a defective lower esophageal sphincter (LES). METHODS: Pigs were studied
      as normal-LES or LES-weakened animals. A novel endoscopic delivery system was
      developed in order to place multiple hydrogel prostheses into the LES submucosa.
      Histopathology sections evaluated ultimate durability and the relationship of the
      prostheses to esophageal anatomy. RESULTS: Overall, 97% of 179 prosthesis
      delivery attempts were successful. LES-weakened animals had LES pressures return
      to normal or supranormal values at 2 weeks and 2 months after prosthesis
      augmentation. Weakened gastric yield pressures improved to normal values at 2
      weeks after prosthesis augmentation. The thickness of the muscular layers and the
      mucosal integrity of the esophagus was unaffected by the retained prostheses.
      CONCLUSIONS: Endoscopically delivered hydrogel prostheses are safe and durable.
      These prostheses can successfully augment a defective sphincter without
      recognizable damage to the esophagus.

PMID- 11839342
TI  - Evaluation of minimally invasive surgical staging for esophageal cancer.
AB  - BACKGROUND: Conventional imaging studies (computed tomography and endoscopic
      esophageal ultrasonography) used for preoperative evaluation of patients with
      esophageal cancer can be inaccurate for detection of small metastatic deposits.
      We evaluated the efficacy of minimally invasive surgical (MIS) staging as an
      additional modality for evaluation of patients with esophageal cancer. METHODS:
      Between December 1998 and February 2001, 33 patients with esophageal cancer were
      evaluated for surgical resection. Conventional imaging studies demonstrated
      operable disease in 31 patients and equivocal findings in 2 patients. All
      patients then underwent MIS staging (laparoscopy, bronchoscopy, and
      ultrasonography of the liver). We compared the results from surgical resection
      and MIS staging with those from conventional imaging. RESULTS: MIS staging
      altered the treatment plan in 12 (36%) of 33 patients; MIS staging upstaged 10
      patients with operable disease and downstaged 2 patients with equivocal findings.
      MIS staging accurately determined resectability in 97% of patients compared with
      61% of patients staged by conventional imaging. The specificity and negative
      predictive value for detection of unsuspected metastatic disease in MIS staging
      were 100% and 96%, respectively, compared with 91% and 65%, respectively, for
      conventional imaging studies. CONCLUSION: In addition to conventional imaging
      studies, MIS staging should be included routinely in the preoperative work-up of
      patients with esophageal cancer.

PMID- 11839344
TI  - Postoperative atrial fibrillation in noncardiothoracic surgical patients.
AB  - BACKGROUND: Atrial fibrillation is a common arrhythmia whose prevalence increases
      with age. It is a well-known complication of cardiothoracic surgery, but the
      incidence and contributing factors to the development of atrial fibrillation in
      noncardiothoracic surgical patients are less well known. This study was
      undertaken to investigate the incidence, association with known risk factors,
      treatment, and outcome of atrial fibrillation in postoperative noncardiac,
      nonthoracic surgical patients. METHODS: A 2-year retrospective review was
      performed of all noncardiac, nonthoracic surgical patients that developed atrial
      fibrillation within 30 days of operation. Incidence, risk factors, treatment and
      outcome related to the development of this arrhythmia were analyzed. RESULTS:
      Fifty-one patients developed atrial fibrillation during this study period for an
      incidence of 0.37%. Most had preexisting cardiac risk factors, a positive fluid
      balance, or had electrolyte or arterial oxygen saturation abnormalities. Two
      thirds were discharged home on new cardiac medications, 16% remained in atrial
      fibrillation, and 12% died. CONCLUSIONS: New onset atrial fibrillation in this
      group of noncardiothoracic surgical patients is an uncommon problem that is a
      morbid event associated with significant mortality.

PMID- 11839343
TI  - A caution regarding lymphatic mapping in patients with colon cancer.
AB  - BACKGROUND: The value of lymphatic mapping and sentinel lymph node biopsy in the
      treatment of colon cancer is controversial. The purpose of this study was to
      determine the accuracy of lymphatic mapping in patients with colon cancer.
      METHODS: Forty-eight patients with colon cancer underwent lymphatic mapping and
      sentinel lymph node biopsy using isosulfan blue dye followed by standard surgical
      resection. The sentinel lymph nodes underwent thin sectioning as will as
      immunohistochemical staining for cytokeratin, in addition to standard hematoxylin
      and eosin staining. RESULTS: In 47 (98%) patients, a sentinel lymph node was
      identified. Sixteen patients had lymph nodes containing metastatic disease, and
      in 6 patients the sentinel lymph node was positive for disease. In no patient was
      the sentinel lymph node the only site of metastatic disease. In 10 patients the
      sentinel lymph node was negative for disease, whereas the nonsentinel lymph nodes
      contained metastatic disease (false negative rate = 38%). CONCLUSIONS: The role
      of lymphatic mapping and sentinel lymph node biopsy in colon cancer is not as
      clear as its role in other tumors. Further large prospective studies are needed
      to evaluate the accuracy and potential benefit of this procedure in patients with
      colon cancer.

PMID- 11839345
TI  - Prospective analysis of endoscopic vein harvesting.
AB  - BACKGROUND: Utilization of bridging vein harvesting (BVH) of saphenous vein
      grafts (SVG) for coronary artery bypass grafting (CABG) results in large wounds
      with great potential for pain and infection. Endoscopic vein harvesting (EVH) may
      significantly reduce the morbidity associated with SVG harvesting. METHODS: A
      prospective database of 200 matched patients receiving EVH and BVH was compared.
      The patients all underwent CABG done over a period of 4 months (April to August
      2000). Patients were excluded if they had prior vein harvesting. RESULTS: The EVH
      and BVH group included 100 patients each with similar demographics. The patients
      in the EVH group had significantly fewer wound complications, mean days to
      ambulation, and total length of stay (P <0.05). There was no difference in
      harvest time or vein injuries. CONCLUSION: Endoscopic vein harvesting results in
      significantly fewer wound complications, decrease in days to ambulation, and the
      total length of stay. EVH is superior to BVH in patients undergoing CABG.

PMID- 11839346
TI  - An ergonomic evaluation of surgeons' axial skeletal and upper extremity movements
      during laparoscopic and open surgery.
AB  - BACKGROUND: Many surgeons have complained of fatigue and musculoskeletal pain
      after laparoscopic surgery. We evaluated differences in surgeons' axial skeletal
      and upper extremity movements during laparoscopic and open operations. METHODS:
      Five surgeons were videotaped performing 16 operations (8 laparoscopic and 8
      open) to record their neck, trunk, shoulder, elbow, and wrist movements during
      the first hour of surgery. We also compared postprocedural complaints of pain,
      stiffness, or numbness between the two groups. RESULTS: Compared with surgeons
      performing open surgery, surgeons performing laparoscopic surgery exhibited less
      lateral neck flexion; less trunk flexion; more internal rotation of the
      shoulders; more elbow flexion; more wrist supination and wrist ulnar and radial
      deviation. There was a trend of more shoulder stiffness after laparoscopic
      operations than after open operations. CONCLUSIONS: Laparoscopic surgery involves
      a more static posture of the neck and trunk, but more frequent awkward movements
      of the upper extremities than open surgery. Ergonomic changes in the operating
      room environment and instrument design could ease the physical stress imposed on
      surgeons during laparoscopic operations.

PMID- 11839347
TI  - Improving operative performance using a laparoscopic hernia simulator.
AB  - BACKGROUND: Traditionally, the acquisition of surgical skill has occurred
      entirely in the operating room. To meet the expanding challenges of cost
      containment and patient safety, novel methods of surgical training utilizing ex
      vivo workstations are being developed. The purpose of our study was to evaluate
      the impact of a laparoscopic training curriculum on surgical residents' operative
      performance. METHODS: Twenty-one surgery residents completed baseline
      laparoscopic total extraperitoneal (TEP) hernia repairs. Operative performance
      was evaluated using a validated global assessment tool. Each resident was then
      randomized to a control group or a trained group. A CD ROM, video, and simulator
      were used for training. At the end of the study, each resident's operative
      performance was again evaluated. RESULTS: Improvement was significantly greater
      in the trained group in five of the eight individual global assessment areas as
      well as the composite score (P <0.05). Questionnaire data suggested that training
      resulted in improved understanding of the TEP hernia repair (P = 0.01) and an
      increased willingness to offer the operation to patients with nonrecurrent
      unilateral hernias (P = 0.02). CONCLUSIONS: A multimodality laparoscopic TEP
      hernia curriculum improves residents' knowledge of the TEP hernia repair and
      comfort in performing the procedure, and may also improve actual operative
      performance.

PMID- 11839348
TI  - Right lower quadrant pain in children caused by omental infarction.
AB  - BACKGROUND: Omental infarction is a rare cause of abdominal pain, with fewer than
      300 cases reported in the literature. Only 15% of reported cases occur in the
      pediatric population. We present our experience with 18 children diagnosed with
      omental infarction admitted to Texas Children's Hospital over a 15-year period.
      STUDY DESIGN: A retrospective review of clinical records, diagnostic images, and
      pathologic findings was carried out for all children diagnosed with isolated
      omental infarction from 1986 to 2000 in order to analyze presenting signs and
      symptoms, preoperative imaging, surgical management, and postoperative outcomes.
      RESULTS: Eighteen children were treated for isolated omental infarction. There
      were 12 boys and 6 girls with an average age of 7.5 years (range 2 to 13). All
      patients presented with acute onset of right lower quadrant pain. Only 5 of 18
      (24%) had associated gastrointestinal symptoms. The average temperature at
      presentation was 99.4 degrees F (+/- 0.78). The average white blood cell count
      was 11.4 (+/- 4.4). Fourteen patients had ultrasonographys performed
      preoperatively: 6 of 14 incorrectly diagnosed appendicitis, 4 of 14 were
      nondiagnostic and 4 of 14 correctly diagnosed omental infarction. Two of 18
      patients underwent computed tomography scans, which were diagnostic for omental
      infarction. Resection of the infarcted omentum was performed in all patients and
      appendectomy in 16 of 18. Thirteen patients underwent an open procedure, 5 were
      performed laparoscopically. There were no postoperative complications. All
      patients had resolution of pain postoperatively and were discharged an average of
      3.0 (+/- 0.9) days after admission. CONCLUSIONS: Omental infarction is an
      uncommon cause of right lower quadrant pain in children and is often diagnosed as
      appendicitis preoperatively. Ultrasonography and computed tomography can be
      diagnostic. Surgical resection of the infarcted omentum results in immediate
      resolution of pain with no morbidity.

PMID- 11839349
TI  - Peptic ulcers in the elderly is a surgical disease.
AB  - BACKGROUND: Operative management for peptic ulcer disease (PUD) has changed
      significantly over the last 30 years. METHODS: For a 15-year period, records of
      patients undergoing operative management for peptic ulcer disease were stratified
      into age groups and examined with respect to presentation, type of operation, and
      risk factors. RESULTS: In all, 154 patients underwent surgery for PUD during the
      1990s. Elderly patients were more likely to require an emergent operation (91%, P
      = 0.005), present with hemodynamic instability (25%, P = 0.025), and have a
      longer hospital stay (21 days, P = 0.012). Among the elderly in the 1990s as
      compared with the 1980s, there was increased use of nonsteroidal anti
      inflammatory drugs ([NSAIDs] (49%, P = 0.005), decreased tobacco use (22%, P =
      0.014), and less likelihood of postoperative renal failure (6%, P = 0.014).
      CONCLUSIONS: Elderly patients in the 1990s comprise the majority of cases
      presenting in a more unstable condition as compared with patients <60 years old,
      but show similar rates of morbidity and mortality. Elderly patients undergoing
      surgery for PUD have shown an increase in use of NSAIDs over the last 15 years.
      The types of procedures have not changed, but operations are more likely to be an
      emergent basis.

PMID- 11839350
TI  - Can we improve trauma mortality in a state with a voluntary trauma system.
AB  - BACKGROUND: Arizona has no organized statewide trauma system. We looked at the
      1997 and the 1998 Uniform Hospital Discharge Data Set (UHDDS) for the State of
      Arizona, and examined the trauma mortality data at both trauma hospitals and
      nontrauma hospitals. METHODS: All qualifying mortalities based on hospital data
      from 1997 through 1998 were reviewed for the State of Arizona. Trauma deaths from
      32 nontrauma hospitals were examined and compared with that of 7 level 1 trauma
      centers within the state. RESULTS: In this time period, there were 375 qualified
      mortalities from nontrauma centers and 761 qualified mortalities from level 1
      trauma facilities. Only 29 (8%) of nontrauma hospital deaths were found to be due
      to motor vehicle accidents. Only 8 (4%) mortalities at nontrauma centers were due
      to firearms. CONCLUSION: The data suggest that patients are arriving at the
      appropriate facility for definitive care despite the absence of a formal
      statewide trauma system.

PMID- 11839351
TI  - Reliable variables in the exsanguinated patient which indicate damage control and
      predict outcome.
AB  - BACKGROUND: Exsanguination as a syndrome is ill defined. The objectives of this
      study were to investigate the relationship between survival and patient
      characteristics--vital signs, factors relating to injury and treatment; determine
      if threshold levels of pH, temperature, and highest estimated blood loss can
      predict survival; and identify predictive factors for survival and to initiate
      damage control. MATERIAL AND METHODS: A retrospective 6-year study was conducted,
      1993 to 1998. In all, 548 patients met one or more criteria: (1) estimated blood
      loss > or =2,000 mL during trauma operation; (2) required > or =1,500 mL packed
      red blood cells (PRBC) during resuscitation; or (3) diagnosis of exsanguination.
      Analysis was made in two phases: (1) death versus survival in emergency
      department (ED); (2) death versus survival in operating room (OR). Statistical
      methods were Fisher's exact test, Student's t test, and logistic regression.
      RESULTS: For 548 patients, mean Revised Trauma Score 4.38, mean Injury Severity
      Score 32. Penetrating injuries 82% versus blunt injuries 18%. Vital statistics in
      emergency department: mean blood pressure 63 mm Hg, heart rate 78 beats per
      minute. Mean OR pH 7.15 and temperature 34.3 degrees C. Mortality was 379 of 548
      (69%). Predictive factors for mortality (means): pH < or =7.2, temperature <34
      degrees C, OR blood replacement >4,000 mL, total OR fluid replacement >10,000 mL,
      estimated blood loss >15 mL/minute (P <0.001). Analysis 1: death versus survival
      in ED, logistic regression. Independent risk factors for survival: penetrating
      trauma, spontaneous ventilation, and no ED thoracotomy (P <0.001; probability of
      survival 0.99613). Analysis 2: death versus survival in OR, logistic regression.
      Independent risk factors for survival: ISS < or =20, spontaneous ventilation in
      ED, OR PRBC replacement <4,000 mL, no ED or OR thoracotomy, absence of abdominal
      vascular injury (P <0.001, max R(2) 0.55, concordance 89%). CONCLUSIONS: Survival
      rates can be predicted in exsanguinating patients. "Damage control" should be
      performed using these criteria. Knowledge of these patterns can be valuable in
      treatment selection.

PMID- 11839353
TI  - Differential repair responses in the coronal and radicular areas of the exposed
      rat molar pulp induced by recombinant human bone morphogenetic protein 7
      (osteogenic protein 1).
AB  - Bone morphogenetic protein 7 (BMP 7), also termed osteogenic protein 1, a member
      of the transforming growth-factor superfamily, was examined for its efficacy in
      inducing reparative dentinogenesis in the exposed pulps of rat molars. To
      determine if the reaction was dose-dependent, collagen pellets containing 1, 3 or
      10 microgram of recombinant BMP 7 were inserted in intentionally perforated pulps
      (10-12 pulps per group) in the deepest part of half-moon class V-like cavities
      cut in the mesial aspect of upper first molars. As controls, the collagen carrier
      (CC group) alone and calcium hydroxide (Ca group) were used as capping agents.
      All cavities were then restored with a glass-ionomer cement. Half of the animals
      were killed after 8 days and the other half after 28 days, by intracardiac
      perfusion of fixative. The molars were processed for histological evaluation by
      light microscopy. No difference in effect could be detected between the three
      concentrations of BMP 7 groups at either time interval. After 8 days, all groups
      showed varying inflammation, from mild of severe, and the Ca group demonstrated
      early formation of a reparative dentine bridge. At 28 days the CC group displayed
      irregular osteodentine formation, leaving some unmineralized areas at the
      exposure site and interglobular unmineralized areas containing pulp remnants. In
      the Ca-treated pulps, the initial formation of thick reparative osteodentine
      bridges that sealed more or less completely the pulp perforation was followed, in
      the deeper part, by irregular tubular dentine. In most BMP 7-treated specimens,
      the initial inflammation has resolved at 8 days and at 28 days heterogeneous
      mineralization or osteodentine filled the mesial coronal pulp. They also had
      complete filling of the radicular pulp by homogenous mineralization in the mesial
      root; this reaction was found in 11 teeth in the BMP 7 group, one tooth in the CC
      group an none of the Ca group. These results emphasize the biological differences
      the coronal and radicular parts of the pulp, and the potential of bioactive
      molecules such as BMP 7 to provide an a alternative conventional endodontic
      treatments.

PMID- 11839354
TI  - Genotyping and antifungal susceptibility of human subgingival Candida albicans
      isolates.
AB  - Subgingival colonization by Candida albicans has been described in human
      immunodeficiency virus (HIV)-infected individuals, but subgingival isolates have
      scarcely been characterized, particularly with respect to genotype and antifungal
      susceptibility. A series of 29 subgingival strains of C. albicans isolated from
      nine HIV-infected individuals was typed by electrophoretic karyotyping and tested
      for susceptibility to fluconazole, itraconazole, the new investigational triazole
      posaconazole and amphotericin B. DNA typing showed genetic heterogeneity within
      subgingival isolates, as almost every individual harbored his/her own specific
      isolate. Genetic identity was usually demonstrated within oral and subgingival
      isolates simultaneously collected from the same individual, but a number of DNA
      types were found to be unique to subgingival strains. These findings suggest that
      colonization is not just the result of Candida spreading from oral surfaces, and
      that subgingivally adapted strains could be involved. All isolates were
      susceptible to all the triazole drugs tested and amphotericin B. Additional
      studies on subgingival Candida colonization and further characterization of
      subgingival isolates are now required to clarify the role of Candida as
      opportunistic periodontal pathogen.

PMID- 11839355
TI  - The influence of density and material on oral perception of ball size with and
      without palatal coverage.
AB  - The size of a bolus determines how it will be manipulated in the mouth and
      swallowed. Ten healthy individuals assessed the size of ball bearings of five
      sizes (4-11 mm diameter) and four materials with different densities in order to
      investigate the effect of weight on oral size perception. To study the role of
      the tongue and palate, the experiment was performed with and without a custom
      made plastic palate. The results revealed that size itself determines size
      perception, and that material and weight are negligible factors. An illusional
      effect in the direction of under-estimation was found for the ball bearings,
      especially for the small sizes up to 8 mm diameter. While wearing a plastic
      palate a significant improvement (P<0.05) occurred; the participants performed
      better and there was less under-estimation. An explanation for this could be that
      only a minor part of the total area of the ball bearing touches the palate and is
      hence detected, while the tongue alone is more compliant and thereby able to
      sense the ball's whole size.

PMID- 11839356
TI  - Alveolar bone remodelling pattern of the rat incisor under different functional
      conditions as shown by minocycline administration.
AB  - Remodelling of the socket surrounding the continuously growing and erupting rat
      incisor was examined in teeth under normo, hyper and hypofunctional conditions.
      Cross-sections of the mandible were observed under fluorescence microscopy, where
      minocycline labelling evidenced bone remodelling. Animals had received
      minocycline (10 mg/day) during the experimental period. Control animals (from all
      three groups) received vehicle alone and samples from these animals were not
      fluorescent. Minocycline did not interfere with the eruption rates in any of the
      functional conditions studied. Normofunctional (impeded) incisors showed constant
      osteogenic activity in the alveolar bone facing the periodontal ligament in all
      regions of the incisor. Under hypofunctional (unimpeded) and hyperfunctional
      (impeded) conditions, osteogenesis in the region close to the alveolar crest was
      markedly increased in the mesial wall of the socket. The labial alveolar bone,
      facing the enamel-related periodontium, was almost entirely formed during the
      experimental period in all the groups, but in hyper and hypofunctional teeth the
      newly formed bone was thicker and contained a substantial amount formed before
      the experimental period. In the more apical regions of the socket no marked
      differences between the three functional conditions were found. The similar bone
      remodelling shown in hypo and hyperfunctional teeth might indicate that there are
      common factors causing this pattern. Consideration of possible factors appear to
      rule out the eruption rate, which is very different under these two functional
      conditions.

PMID- 11839357
TI  - A new frameshift mutation encoding a truncated amelogenin leads to X-linked
      amelogenesis imperfecta.
AB  - The amelogenin proteins are the most abundant organic components of developing
      dental enamel. Their importance for the proper mineralization of enamel is
      evident from the association between previously identified mutations in the X
      chromosomal gene that encodes them and the enamel defect amelogenesis imperfecta.
      In this investigation, an adult male presenting with a severe hypoplastic enamel
      phenotype was found to have a single base deletion at the codon for amino acid
      110 of the X-chromosomal 175-amino acid amelogenin protein. The proband's mother,
      who also has affected enamel, carries the identical deletion on one of her X
      chromosomes, while the father has both normal enamel and DNA sequence. This
      frameshift mutation deletes part of the coding region for the repetitive portion
      of amelogenin as well as the hydrophilic tail, replacing them with a 47-amino
      acid segment containing nine cysteine residues. While greater than 60% of the
      protein is predicted to be intact, the severity of this phenotype illustrates the
      importance of the C-terminal region of the amelogenin protein for the formation
      of enamel with normal thickness.

PMID- 11839358
TI  - Changes in tooth position in humans in relation to arterial blood pressure.
AB  - The three-dimensional physiological tooth movement synchronized with the
      heartbeat is called periodontal pulsation. This study utilized a computer
      assisted amorphous sensor to evaluate the relation between tooth position and
      arterial blood pressure, and also between the amplitude of periodontal pulsation
      and arterial blood pressure. The measuring device consisted of a small magnet
      attached to the tooth and an amorphous sensor that was used to detect
      displacement of the tooth without actually contacting it. The sample consisted of
      the upper left central incisors of six healthy Japanese volunteers. The three
      measuring points for each tooth were on the labial surface. The cold-pressor test
      was used as an autonomic nerve stimulus that induces an increase in blood
      pressure and heart rate. Periodontal pulsation, electrocardiogram, blood pressure
      and heart rate were recorded simultaneously during a 1 min pre-test relaxation, a
      2 min cold-pressor test and a 1 min recovery. The results showed significant
      correlations between tooth position and mean blood pressure in five of the six
      volunteers and between tooth position and pulse pressure in four. Moreover, it
      was confirmed that tooth position shifted in the labial direction in conjunction
      with an increase of the mean blood pressure induced by cold stimulation.
      Significant correlations were found between the amplitude of periodontal
      pulsation and pulse pressure in four of the volunteers. These findings suggest
      that in humans tooth position might be affected by the force of blood pressure
      transmitted through periodontal vessels and that the amplitude of periodontal
      pulsation tends to reflect changes of pulse pressure rather than changes in mean
      blood pressure.

PMID- 11839359
TI  - Growth-associated protein-43 immunohistochemical and ultrastructural changes in
      jaw muscle spindles of the rat following loss of occlusion.
AB  - The effects of complete loss of occlusion on the structural and functional status
      of these muscle spindles were investigated by immunohistochemistry either for
      protein gene product 9.5 (PGP 9.5) or growth-associated protein-43 (GAP-43) by
      light and electron microscopy. All the upper molars of 4-week-old Wistar rats
      were extracted and the erupted portions of the upper and lower incisors of the
      same animals were cut-off at the level of the interdental papilla every other
      day. In a control group, immunoreactivity for GAP-43 was positive in the
      developing annulospiral endings of 2-week-old rats, but was not detected in any
      of the muscle spindles after 3 weeks of age. At 4 weeks of age, the PGP 9.5
      immunostained spindles had well-differentiated annulospiral endings.
      Ultrastructurally, these afferent endings showed lenticular or circular profiles
      in cross-sections, and were differentially indented into the intrafusal-fibres.
      The inner surfaces of the terminals formed rather smooth myoneural junctions,
      while the outer surfaces were covered only by basal lamina continuous with that
      of the underlying intrafusal muscle fibres. After the experimental elimination of
      occlusal contact, GAP-43 immunoreactivity reappeared in some nerve endings of
      muscle spindles by 3 days, and persisted for at least 28 days. During this
      period, the afferent-terminals exhibited various fine structural abnormalities
      such as irregular outlines and invaginated neuromuscular interfaces. Some sensory
      terminal (ST) profiles were completely engulfed by intrafusal-fibres. However,
      GAP-43 expression and ultrastructural alterations became undetectable within a
      week of the end of incisal cutting and the recovery of incisal-contact. These
      data indicate that remodelling of nerve terminals in muscle spindles, as assessed
      by GAP-43 expression and ultrastructural changes, occurs soon after a loss of
      occlusion, and ceases if incisal-contact is restored. It is concluded that
      possible changes in jaw muscle function, as well as a sudden loss of
      proprioceptive sensory input from the periodontal mechanoreceptors of molars and
      incisors, induce the structural reorganisation of nerve terminations in jaw
      muscle spindles that is associated with the appearance and disappearance of GAP
      43 immunoreactivity.

PMID- 11839360
TI  - Tissue oxygen tension and blood-flow changes in rat incisor pulp with graded
      systemic hyperoxia.
AB  - The role of oxygen in the regulation of the pulpal microcirculation is unknown.
      This investigation is aimed to measure tissue oxygen tension and blood-flow
      changes in the pulp of rat lower incisors during graded systemic hyperoxia, and
      to determine the response of the pulpal vasculature to various oxygen tensions.
      Twenty-four Sprague-Dawley rats were anaesthetized and artificially ventilated
      with the appropriate gas mixture. Recessed oxygen-sensitive microelectrodes were
      used to measure pulpal tissue oxygen tension via a small access cavity filled
      with saline on the labial surface of the incisor. A laser Doppler flowmeter was
      used to record pulpal blood-flow. Inspired oxygen was increased stepwise from 20
      to 100% in 20% steps. Systemic blood-gas concentrations were measured at each
      step. Systemic arterial oxygen tension at 100% oxygen ventilation reached 481.2
      +/- 30.7% of the baseline at 20% oxygen breathing (n=21). Pulpal tissue oxygen
      tension did not change significantly whereas pulpal blood-flow fell dose
      dependently to 74.6 +/- 5.0% at 100% oxygen ventilation (n=21). Systemic
      hyperoxia, therefore, induces a significant reduction in pulpal blood-flow
      whereas pulpal tissue oxygen tension remains relatively stable, indicating an
      oxygen-dependent local regulatory mechanism.

PMID- 11839362
TI  - Magnetic resonance spectroscopy: current and future applications in psychiatric
      research.
AB  - Magnetic resonance spectroscopy (MRS) provides a useful method for studying a
      number of psychotropic medications and metabolites in human brain in vivo. New
      insights regarding the pharmacokinetic and pharmacodynamic properties of
      psychotropic medications in the target organ (i.e., brain) have been obtained
      using lithium-7 MRS and fluorine-19 MRS. Both proton and phosphorus-31 MRS have
      significantly enhanced our knowledge of the pathophysiology of a number of
      psychiatric disorders by providing estimates of brain concentrations of several
      important cerebral metabolites. Efforts are also being made to link MRS measures
      of cerebral metabolism with neurophysiologic and neurocognitive processes.
      Ongoing improvement and refinement in MRS techniques, including the installation
      of scanners with increased magnetic field strength and better methods of data
      processing, will improve both spatial and temporal resolution. In addition,
      efforts to develop multisite research studies may result in greater
      standardization of MRS procedures and methods for interpretation of results. In
      this review, the current status of MRS applications in psychiatric research is
      reviewed, and new frontiers and possible future developments are discussed.

PMID- 11839361
TI  - Inhibition of osteoclastogenesis by the secretion of osteoprotegerin in vitro by
      rat dental follicle cells and its implications for tooth eruption.
AB  - Tooth eruption requires the presence of the dental follicle, a loose connective
      tissue sac that surrounds each unerupted tooth. Early postnatally in the rat, the
      follicle secretes colony-stimulating factor-1 (CSF-1) and monocyte chemotactic
      protein-1 (MCP-1), chemotactic molecules that are probably responsible for the
      recruitment of mononuclear cells. These cells, in turn, fuse to form osteoclasts,
      which are required for alveolar bone resorption to form an eruption pathway.
      Recent studies have shown that the osteoprotegerin (OPG) gene is expressed in the
      dental follicle, but in the first mandibular molar of the rat, that expression is
      reduced at day 3, the time of maximal osteoclast numbers on the alveolar bone.
      Inhibition of OPG expression at this time would allow osteoclast
      formation/activation. To determine if the dental follicle cells do secrete OPG
      that inhibits osteoclastogenesis, spleen cell cultures were established and
      soluble osteoclast differentiation factor (ODF) and CSF-1 added to some of them
      to promote osteoclast formation. In other cultures, dental follicle cells were
      added in an insert, such that they did not touch the spleen cells. Using a
      quantitative, tartrate-resistant acid phosphatase (TRAP) assay, it was shown that
      ODF and CSF-1 promoted osteoclastogenesis in the spleen cell cultures, but the
      addition of the follicle cells inhibited this and returned the TRAP activities to
      those seen in cultures of spleen cells only. Adding anti-OPG to these cultures,
      however, negated the effect of the follicle cells, demonstrating that OPG was the
      inhibitory molecule secreted by those cells. The follicle cells also
      immunostained for OPG, confirming that they synthesize OPG. These findings,
      coupled with those of other studies which show that the periodontal ligament (a
      derivative of the dental follicle) also secretes OPG, indicate that, except for
      the period of time in tooth eruption, where osteoclast formation is needed to
      form an eruption pathway, secretion of OPG would be the norm, presumably to
      prevent resorption of alveolar bone and subsequent disruption of the periodontal
      ligament.

PMID- 11839364
TI  - Neural correlates of refixation saccades and antisaccades in normal and
      schizophrenia subjects.
AB  - BACKGROUND: Schizophrenia subjects demonstrate difficulties on tasks requiring
      saccadic inhibition, despite normal refixation saccade performance. Saccadic
      inhibition is ostensibly mediated via prefrontal cortex and associated
      cortical/subcortical circuitry. The current study tests hypotheses about the
      neural substrates of normal and abnormal saccadic performance among subjects with
      schizophrenia. METHODS: Using functional magnetic resonance imaging, blood
      oxygenation level-dependent (BOLD) data were recorded while 13 normal and 14
      schizophrenia subjects were engaged in refixation and antisaccade tasks. RESULTS:
      Schizophrenia subjects did not demonstrate the increased prefrontal cortex BOLD
      contrast during antisaccade performance that was apparent in the normal subjects.
      Schizophrenia subjects did, however, demonstrate normal BOLD contrast associated
      with refixation saccade performance in the frontal and supplementary eye fields,
      and posterior parietal cortex. CONCLUSIONS: Results from the current study
      support hypotheses of dysfunctional prefrontal cortex circuitry among
      schizophrenia subjects. Furthermore, this abnormality existed despite normal BOLD
      contrast observed during refixation saccade generation in the schizophrenia
      group.

PMID- 11839363
TI  - Structural brain abnormalities in patients with schizophrenia and 22q11 deletion
      syndrome.
AB  - BACKGROUND: 22q11 Deletion Syndrome is a genetic syndrome associated with an
      increased risk for developing schizophrenia. Brain abnormalities have been
      reported in 22q11 Deletion Syndrome, but little is known about whether
      differences in brain structure underlie the psychotic disorders associated with
      this syndrome. In the current study, we used magnetic resonance imaging to
      characterize the structural brain abnormalities found in adults who have both
      22q11 Deletion Syndrome and schizophrenia. METHODS: Magnetic resonance imaging
      brain scans of 14 adults (7 male, 7 female) with 22q11 Deletion Syndrome and
      schizophrenia and 14 age- and gender-matched healthy volunteers were analyzed to
      derive measures of gray matter, white matter, and cerebrospinal fluid.
      Differences between the two groups were tested using student t tests. RESULTS:
      22q11 Deletion Syndrome and schizophrenia subjects had significantly smaller
      total gray matter volume (t = 2.88, p <.01) and larger lateral ventricles (t =
      4.08, p <.001) than healthy controls. Gray matter deficits were most prominent in
      the frontal and temporal lobes. Total white matter volumes did not differ between
      the two groups. CONCLUSIONS: Findings from this 22q11 Deletion Syndrome and
      schizophrenia study are similar to those reported in other patients with
      schizophrenia, but only partially consistent with those reported in nonpsychotic
      children with 22q11 Deletion Syndrome. 22q11 Deletion Syndrome may provide a
      valuable genetic neurodevelopmental model for investigating the relationship
      between abnormalities in brain development and the expression of schizophrenia.

PMID- 11839365
TI  - Biochemical markers of mood: a proton magnetic resonance spectroscopy study of
      normal human brain.
AB  - BACKGROUND: Elevated brain Cho has been shown within the basal ganglia and
      frontal (i.e., orbitofrontal and cingulate) cortices in patients with mood
      disorders utilizing Proton Magnetic Resonance Spectroscopy (1H-MRS). We sought to
      determine the relationship between Cho and mood in a cohort of healthy young
      subjects. METHODS: Twenty-seven subjects without neurologic or psychiatric
      disorders were evaluated with the Positive and Negative Affect Scale and
      underwent 1H-MRS of bilateral frontal and occipito-parietal white matter.
      RESULTS: We found that Cho in the left frontal lobe was inversely correlated with
      Positive Affect [F(1,24) = 19.2, p <.001, r(2) =.45]. CONCLUSIONS: Our results
      highlight the important involvement of Cho underlying the integration of
      affective processing within prefrontal circuitry, and may indicate increased
      myelin turnover in subjects with lower Positive Affect. Further efforts will be
      necessary to determine if high Cho is associated with increased incidence of mood
      disorders throughout life.

PMID- 11839366
TI  - Electroencephalographic sleep profiles in single-episode and recurrent unipolar
      forms of major depression: II. Comparison during remission.
AB  - BACKGROUND: Previous studies indicate that recurrent forms of depression are
      associated with greater biological disturbances as compared to single-episode
      cases. This study examines whether the observed differences in the sleep patterns
      during recurrent and single-episode depression persist into remission following
      nonpharmacologic treatment. METHODS: Two groups of patients (27 single episode
      [SE] and 53 recurrent unipolar [RU]) with major depression underwent sleep
      studies before and after nonpharmacologic treatment. Groups were equated for age,
      severity, and proportion of men and women. Groups were compared using
      multivariate analyses of covariance and/or analyses of covariance to examine six
      sets of sleep measures. RESULTS: The differences observed between the SE and RU
      groups during the index episode persisted into early remission. The findings of
      greater disturbances of sleep continuity, rapid eye movement sleep and diminished
      slow wave sleep in the RU group supports the hypothesis that recurrent depression
      is associated with a more severe neurophysiological substrate than clinically
      comparable SE cases. CONCLUSIONS: Although these observations are consistent with
      an illness progression model, the possibility that recurrent affective illness is
      associated with a more virulent, stable phenotype cannot be ruled out. Resolution
      of this issue requires longitudinal and family studies.

PMID- 11839367
TI  - Regional cerebral glucose utilization in patients with a range of severities of
      unipolar depression.
AB  - BACKGROUND: Patients with unipolar depression are most often reported to have
      decreased regional cerebral glucose metabolism (rCMRglu) in dorsal prefrontal and
      anterior cingulate cortices compared with healthy control subjects, often
      correlating inversely with severity of depression. METHODS: We measured rCMRglu
      with fluorine-18 deoxyglucose positron emission tomography (PET) in 38 medication
      free patients with unipolar depression and 37 healthy control subjects performing
      an auditory continuous performance task to further investigate potential
      prefrontal and anterior paralimbic rCMRglu abnormalities in patients attending to
      this task. RESULTS: Compared with control subjects, the subgroup of patients with
      Hamilton depression scores of 22 or greater demonstrated decreased absolute
      rCMRglu in right prefrontal cortex and paralimbic/amygdala regions as well as
      bilaterally in the insula and temporoparietal cortex (right > left); they also
      exhibited increased normalized metabolic activity bilaterally in the cerebellum,
      lingula/cuneus, and brain stem. Severity of depression negatively correlated with
      absolute rCMRglu in almost the entire extent of the right cingulate cortex as
      well as bilaterally in prefrontal cortex, insula, basal ganglia, and
      temporoparietal cortex (right > left). CONCLUSIONS: Areas of frontal, cingulate,
      insula, and temporal cortex appear hypometabolic in association with different
      components of the severity and course of illness in treatment-resistant unipolar
      depression.

PMID- 11839368
TI  - Clinical predictors of response to lamotrigine and gabapentin monotherapy in
      refractory affective disorders.
AB  - BACKGROUND: The objective of the current study was to examine possible clinical
      predictors of positive response to lamotrigine or gabapentin monotherapy in
      treatment-refractory affectively ill patients. METHODS: Forty-five patients with
      treatment refractory bipolar (n = 35) or unipolar (n = 10) affective disorder
      participated in a clinical study evaluating six weeks of treatment with
      lamotrigine, gabapentin, or placebo monotherapy given in a double-blind,
      randomized fashion with two subsequent cross-overs to the other agents. Patients
      received daily mood ratings and weekly cross-sectional scales. Much or very much
      improved on the Clinical Global Impression scale modified for bipolar illness was
      considered a positive response. Degree of response was correlated with a number
      of baseline demographic and course of illness variables in a univariate analysis
      and then by linear regression. RESULTS: Response rates to lamotrigine (51%)
      exceeded those to gabapentin (28%) and placebo (21%). A positive response to
      lamotrigine monotherapy was associated with a bipolar diagnosis; fewer
      hospitalizations; fewer prior medication trials; and male gender (of which the
      latter two variables survived logistic regression). For gabapentin, degree of
      response correlated with shorter duration of illness; younger age; and lower
      baseline weight (with the latter two surviving linear regression). CONCLUSIONS:
      In this highly treatment-refractory population, lamotrigine appeared most
      effective for male patients with fewer prior medication trials. Gabapentin
      monotherapy, although not better than placebo, appeared most effective in those
      with younger age and lower baseline weight. These preliminary data in a treatment
      refractory subgroup may help in the further definition of the range of clinical
      utility of these widely used anticonvulsants.

PMID- 11839369
TI  - Interactive effect of cytochrome P450 17alpha-hydroxylase and dopamine D3
      receptor gene polymorphisms on abnormal involuntary movements in chronic
      schizophrenia.
AB  - BACKGROUND: Tardive dyskinesia is a chronic adverse effect of anti psychotic
      drugs, where association with a polymorphic site in the dopamine D3 receptor gene
      has been previously reported. Cytochrome P 450 17alpha-hydroxylase activity has
      been implicated with modulation of central dopamine release as well as
      neuroprotection. We investigated the association of a T -->C variation in the
      cytochrome P 450 17alpha-hydroxylase gene with tardive dyskinesia in patients
      with chronic schizophrenia. METHODS: Cytochrome P 450 17 allele and genotype
      frequencies were compared between matched schizophrenia patients with (n = 55) or
      without tardive dyskinesia (n = 58). Interactive effects of cytochrome P 450
      17alpha-hydroxylase with the dopamine D3 Ser9Gly polymorphism on abnormal
      involuntary movements were examined. RESULTS: There was no difference in
      cytochrome P 450 17alpha-hydroxylase genotype distribution between patients with
      and without tardive dyskinesia; however, patients carrying the cytochrome P 450
      17alpha-hydroxylase A2-A2 genotype and the dopamine D3gly allele had the highest
      orofacial (p <.04), distal (p <.05), and incapacitation (p <.04) scores on the
      Abnormal Involuntary Movements Scale. CONCLUSIONS: Schizophrenia patients who
      carry the dopamine D3gly allele and the cytochrome P 450 17alpha-hydroxylase A2
      A2 genotype may be more likely to develop abnormal orofoacial and distal
      involuntary movements and to be incapacitated by these movements when chronically
      exposed to classical antipsychotic drugs.

PMID- 11839371
TI  - Reactivity of serotonin in whole blood.

PMID- 11839370
TI  - Possible association of QTc interval prolongation with co-administration of
      quetiapine and lovastatin.
AB  - BACKGROUND: QTc interval prolongation can occur as a result of treatment with
      both conventional and novel antipsychotic medications and is of clinical concern
      because of its association with the potentially fatal ventricular arrhythmia,
      torsade de pointes. METHODS: One case is described in which a patient with
      schizophrenia, who was being treated for dyslipidemia, developed a prolonged QTc
      interval while taking quetiapine and lovastatin. RESULTS: QTc returned to
      baseline when the lovastatin dose was reduced. CONCLUSIONS: QTc prolongation
      associated with antipsychotic medication occurs in a dose-dependent manner. We
      therefore hypothesize that the addition of lovastatin caused an increase in
      plasma quetiapine levels through competitive inhibition of the cytochrome P(450)
      (CYP) isoenzyme 3A4. Our case highlights the potential for a drug interaction
      between quetiapine and lovastatin leading to QTc prolongation during the
      management of dysipidemia in patients with schizophrenia.

PMID- 11839374
TI  - Mix-ups and mycoplasma: the enemies within.
AB  - Human leukemia-lymphoma (LL) cell lines represent important tools for
      experimental research. Among the various problems associated with cell lines, the
      two most common concern contaminations: (1) cross-contamination with unrelated
      cells and (2) contamination with microorganisms, in particular mycoplasma. The
      bad news is that about one-third of the cell lines are either cross-contaminated
      or mycoplasma-infected or both. The good news is that there are means to
      recognize and overcome these problems. In cases where, during attempts to
      establish new LL cell lines, primary LL cultures are cross-contaminated with
      continuous cell lines, intended new cell lines simply cannot be established
      ("early" cross-contamination). In cases of "late" cross-contamination of existing
      LL cell lines where the intrusive cells have a growth advantage, the original
      ("uncontaminated") cell lines may still be available elsewhere. DNA
      fingerprinting and cytogenetic analysis appear to be the most suitable approaches
      to detect cross-contaminations and to authenticate LL cell lines. A different but
      related aspect of "false" LL cell lines is the frequent misclassification of cell
      lines whereby the actual cell type of the cell line does not correspond to the
      purported model character of the cell line. Mycoplasma infection can have a
      multitude of effects on the eukaryotic cells which, due to the variety of
      infecting mycoplasma species and many other contributing parameters, cannot be
      predicted, rendering resulting data questionable at best. Practical procedures
      for the detection and elimination of mycoplasma contamination have been
      developed. Diagnostic and preventive strategies in order to hem the alarming
      increase in "false" and mycoplasma-positive LL cell lines are recommended.

PMID- 11839375
TI  - PCR-heteroduplex analysis of TCR gamma, delta and TAL-1 deletions in T-acute
      lymphoblastic leukemias: implications in the detection of minimal residual
      disease.
AB  - Detection of MRD remains one of the major goals in the treatment of acute
      lymphoblastic leukemia (ALL). We have used the polymerase chain reaction (PCR)
      heteroduplex (HD) analysis to assess and confirm the clonal expansion of T cell
      receptor (TCR) gamma and delta gene rearrangements in 24 T-ALL patients at
      diagnosis. 52.4% revealed Vdelta1-Jdelta1; 48% Vdelta2-Ddelta3; 62.5% Vgamma1
      Jgamma1 and 46% both Vdelta1-Jdelta1 and Vgamma1-Jgamma1 clonal rearrangements.
      6/24 patients had TAL-1 deletion. These clonal markers were used to monitor MRD
      in remission/relapse bone marrow samples for periods ranging from 6 to 75 months
      after diagnosis. Patients who relapsed and died revealed a continuous PCR-HD
      positivity in their clinical remission bone marrow samples. HD analysis
      established identical diagnostic clone at relapse. Patients who are in long-term
      clinical and morphological remission achieved PCR-HD negativity in their 8-12
      months bone marrow remission samples and continue to be PCR-HD negative. MRD
      monitored in six patients with two diagnostic PCR--HD positive clonal markers
      reveal an identical pattern ensuring circumvention of false positive and negative
      results. Thus, we conclude that PCR followed by HD analysis is a useful technique
      to monitor MRD in remission/relapse samples in ALL patients.

PMID- 11839376
TI  - A novel predictive model of outcome in de novo AML based on S-phase activity and
      proliferative response of blast cells to haemopoietic growth factors.
AB  - This study assesses whether the kinetic response of AML cells to HGFs might help
      to predict initial clinical outcome of treatment in de novo AML in association
      with age, FAB type and karyotype. Best subset regression analysis indicated
      optimal variables to develop models to predict prognosis. High S-phase in
      surviving cells following 7 days incubation in SFM, resistance to stimulation by
      G+GM-CSF and poor karyotype taken in combination correctly predicted outcome in
      83% of patients. The importance of high SFM S-phase may be to indicate autonomous
      proliferation therefore a leukemic clone more likely to regenerate following
      therapy at the expense of normal haemopoiesis. Kinetic studies of AML cells may
      be a useful predictor of outcome in addition to other more established prognostic
      factors.

PMID- 11839377
TI  - Peripheral blood leucocytes ornithine decarboxylase activity in chronic myeloid
      leukemia patients: prognostic and therapeutic implications.
AB  - Leukocytes ornithine decarboxylase (ODC) activity was measured in normal
      individuals and in patients with chronic myeloid leukemia (CML) in chronic phase
      (CML-CP) as well as in accelerated phase (CML-AP), with an aim to examine the
      role of ODC activity in prognostic evaluation of CML patients. Our results showed
      that ODC activity was significantly higher in CML-CP (41.02+/-25.57nmol/h per
      10(7) cells, P<0.005) and CML-AP (67.71+/-44.42nmol/h per 10(7) cells, P<0.001)
      patients than in normal subjects (3.12+/-1.34nmol/h per 10(7) cells).
      Furthermore, patients with CML-AP showed higher ODC activity than CML-CP patients
      (P<0.005). Patients with CML-CP who converted to accelerated phase within 24
      months had higher ODC activity (84.58+/-12.81nmol/h per 10(7) cells) than
      patients who did not convert to accelerated phase (31.13+/-18.24nmol/h per 10(7)
      cells). The high value of ODC activity was also associated with less clinico
      hematological response. We suggest that ODC activity reflects the neoplastic
      proliferative activity in CML patients and may serve as an additional prognostic
      marker.

PMID- 11839378
TI  - Fatigue as an important aspect of quality of life in patients with acute myeloid
      leukemia.
AB  - Quality of life (QL) was evaluated in 101 patients with AML undergoing intensive
      and prolonged treatment at 12 sequential time points by using the European
      Organization for Research and Treatment of Cancer (EORTC) QLQ-C 30 questionnaire
      and the profile of mood states scale (POMS). For those patients having completed
      the course of inpatient treatment (n=37), QL improved from the beginning of
      chemotherapy to the end of inpatient treatment. Patients who subsequently went
      off protocol did not differ significantly in their self-assessed QL when compared
      with patients who completed therapy. Fatigue was more closely related to QL than
      nausea/emesis or appetite loss, but did not correlate with hemoglobin levels.

PMID- 11839379
TI  - The effect of chemical blockade of PKC with Go6976 and Go6983 on proliferation
      and MAPK activity in IL-6-dependent plasmacytoma cells.
AB  - Interleukin-6 (IL-6) mediates growth of murine B9 hybridoma/plasmacytoma cells
      via Ras-dependent mitogen-activated protein kinase (MAPK) pathway. Preincubation
      of cells with selective protein kinase C (PKC) inhibitors Go6976 and Go6983 leads
      to enhancement of IL-6-induced p44/p42 MAPK activity. The basal p44/p42 MAPK
      activity is also stimulated in the presence of both inhibitors. On the other
      hand, Go6976 completely blocks proliferation, but Go6983 which does not inhibit
      PKC(mu) has no effect on the cell growth. These findings suggest that PKC(mu) is
      required for proliferation and other PKC isoenzymes are involved in regulation of
      IL-6-dependent growth of B9 cells by negative regulation of the MAPK pathway.

PMID- 11839380
TI  - Long-term bone marrow culture-derived stromal fibroblasts as a potential target
      for gene therapy in acute myelogenous leukemia.
AB  - As a part of our continuing efforts to develop gene therapy for acute myelogenous
      leukemia (AML), this study was undertaken to evaluate the possibility of using
      autologous bone marrow stromal fibroblasts (BMSFs) as a target cell population.
      Autologous BMSFs in AML were isolated from the stromal layers of long-term bone
      marrow culture (LTBMC) using immunomagnetic beads. BMSFs exhibited rapid
      proliferation even in the absence of growth factors. Cultures stimulated with
      bFGF produced significantly increased numbers of BMSFs than cultures without
      added growth factors. Using LNC/LacZ retroviral vector, the transduction
      efficiency of BMSFs was 13+/-4% at a 5 multiplicity of infection (MOI).
      LNC/interleukin-2 (IL-2)-transduced BMSFs produced between 1200 and 4800pg of IL
      2/10(6) cells per 24h. Using adenoviral vector AdV/LacZ, the transduction
      efficiency was 84+/-10% at 100, and 92+/-8% at a MOI of 1000. Although the
      addition of basic fibroblast growth factor, epidermal growth factor, or platelet
      derived growth factor did not affect the transduction efficiency, they increased
      the numbers of transduced cells significantly (P<0.01). AdV/IL-2-treated BMSFs
      produced high levels of IL-2 over the course of 7 days between 9820 and 22,700pg
      of IL-2/10(6) cells per 24h. Our finding that the genetically engineered
      autologous BMSFs of AML could be successfully established in vitro implies that
      BMSFs obtained from LTBMC might be considered as a target cell population for
      certain types of clinical gene therapy in AML.

PMID- 11839381
TI  - Clone and expression of mutant M-CSF and its receptor from human leukemic cell
      line J6-1.
AB  - Macrophage colony-stimulating factor (M-CSF) plays important roles in
      hematopoietic and immunologic systems. Some isoforms or mutations have been
      demonstrated including membrane-bound and cellular M-CSF, which associated with
      some leukemia, lymphoma and other solid tumors. We previously reported that the M
      CSF-like membrane-associated factor (MAF-J6-1) and its receptor was found from
      human leukemic cell line J6-1. In this report, the cDNA of MAF-J6-1 and its
      receptor were cloned. The cDNA sequence of MAF-J6-1 shows a 768bp open reading
      frame (ORF) with 99.2% homology to m-M-CSF, but six site mutations, including two
      synonymous mutations and four missense mutations. The cDNA of MAF-J6-1-R has a
      2916bp ORF shared 99.6% homology with M-CSF-R, but 13 site mutations, including
      six synonymous mutations and seven missense mutations. At the same time, a 1662bp
      mutant s-M-CSF cDNA, which has 10 site mutations including three synonymous
      mutations and seven missense mutations, was cloned from J6-1 cells. The cDNAs of
      MAF-J6-1 and MAF-J6-1-R were inserted into a mammalian expression plasmid pTARGET
      and were expressed in COS-7 cells that demonstrated by their specific MAb. COS-7
      cells transfected with MAF-J6-1-R show obvious protein tyrosine kinase (PTK)
      activity. Our present work shows that MAF-J6-1 and its receptor are mutations of
      M-CSF and its receptor.

PMID- 11839382
TI  - Inhibiting effects on the induction of cytotoxic T lymphocytes by dendritic cells
      pulsed with lysates from acute myeloid leukemia blasts.
AB  - Dendritic cells (DCs) were established from 25 patients in complete remission of
      acute myeloid leukemia (AML). In patients during hematopoietic regeneration
      following chemotherapy the yield of DC was comparable to that of healthy donors.
      In patients, more than 2 months after chemotherapy, significantly less DC were
      generated. Comparison of the antigen-presenting capacity using tetanus toxoid of
      six AML patients and six healthy volunteers did not show significant differences.
      In six AML patients, lymphocytes stimulated with blast cell lysate pulsed DC were
      analyzed for cytotoxic activity against autologous blast cells. 8.4-35.6% of
      autologous blast cells were lysed by DC stimulated lymphocytes. In three of the
      six patients maximum lysis of target cells was achieved by unpulsed DC. Thus, it
      seems that in some patients blast cell lysates mediate inhibitory effects, which
      may explain to some extend immune escape mechanisms in AML.

PMID- 11839383
TI  - Arsenic trioxide and methylprednisolone use different signal transduction
      pathways in leukemic differentiation.
AB  - Certain cell lines like HL 60 and K 562 are utilised as leukemic cell models for
      leukemogenesis research, which differentiate along the granulocytic and/or
      monocytic pathway when treated with certain inducer molecules. High dose
      methylprednisolone treatment has been shown to induce in vivo and in vitro
      differentiation of myeloid leukemia cells to mature granulocytes in patients with
      acute promyelocytic leukemia (APL) and other subtypes of acute myeloid leukemia
      (AML). Arsenic trioxide (As(2)O(3)) has been confirmed to have remission
      induction effects on APL. However, there are conflicting results on the effects
      with other AML subtypes. Also, it has been well established that the reversible
      phosphorylation of proteins is a major regulatory mechanism in the signal
      transduction pathways that control cell growth and differentiation.
      Serine/threonine protein phosphatases (PP) are major components of
      phosphorylation. In this study, we investigated the effect of As(2)O(3) on HL 60
      and K 562 myeloid leukemic differentiation and compared the signalling cascades
      of the two inducers with respect to serine/threonine PP 1 and 2A. We utilised PP1
      and PP2A inhibitors okadaic acid and calyculin A. In contrast to
      methylprednisolone, there was no effect of phosphatase inhibitors on As(2)O(3)
      induced leukemic differentiation. Incomplete leukemic differentiation occurred
      with lower As(2)O(3) concentration as 10(-6)M. Unlike As(2)O(3),
      methylprednisolone induced complete granulocytic and/or monocytic differentiation
      of HL 60 and K 562 cells via upregulation of PP2A regulatory subunits. Therefore,
      As(2)O(3) and methylprednisolone are promising agents that have the potential to
      be used together in myeloid leukemic differentiation therapy.

PMID- 11839385
TI  - Immunotherapy for multiple myeloma: insights from other models.

PMID- 11839384
TI  - Comparison between pediatric acute myeloid leukemia (AML) and adult AML in VEGF
      and KDR (VEGF-R2) protein levels.
AB  - We reported previously that high levels of vascular endothelial growth factor
      (VEGF) were associated with shorter survival in adult acute myeloid leukemia
      (AML) patients. In this study, cellular VEGF and its receptor, VEGF-R2 (kinase
      domain receptor (KDR)), were analyzed in 45 pediatric AML patients using Western
      blot and solid-phase radioimmunoassay (RIA). Cellular VEGF levels were
      significantly lower in pediatric AML compared to adult AML patients. In contrast,
      there was no significant difference in VEGF-R2 levels between adult and pediatric
      AML. Higher VEGF and VEGF-R2 levels in pediatric AML patients correlated with
      higher white blood cell (WBC). Unlike in adults, VEGF and VEGF-R2 levels in
      pediatric AML patients did not correlate with survival. This data suggest that
      the role of VEGF and its receptor VEGF-R2 in pediatrics AML may be different from
      that in adult AML.

PMID- 11839386
TI  - Understanding the action of interferon in hairy cell leukemia: the past as
      prologue.

PMID- 11839387
TI  - Dendritic cell generation for leukemia immunotherapy.

PMID- 11839388
TI  - Chemotherapy-induced immunosuppression and reconstitution of immune function.

PMID- 11839389
TI  - Sphingosine kinase inhibitors in the apoptosis of leukaemia cells.

PMID- 11839390
TI  - Coexistence of independent myelodysplastic and Philadelphia chromosome positive
      clones in a patient treated with hydroxyurea.
AB  - We report a patient with Philadelphia chromosome positive (Ph +ve) chronic
      myelogenous leukemia (CML), treated with hydroxyurea alone, who upon disease
      progression developed an additional Ph - ve clone containing chromosomal
      abnormalities typical of myelodysplastic syndrome (MDS). Retrospective analysis
      of a cryopreserved stem cell specimen from diagnosis confirmed that this second
      clone developed during the course of treatment. The development of a clone with
      additional cytogenetic abnormalities in CML has only been reported after
      leukemogenic treatment, stem cell transplantation or interferon. We report a case
      of secondary Ph - ve MDS/AML during blast crisis in a patient treated with
      hydroxyurea for CML.

PMID- 11839392
TI  - Expression of nuclear factor kappa B components in human endometrium.
AB  - Nuclear factor kappa B (NFkappaB) is a family of transcription factors involved
      in signalling between IL1 and TNFalpha receptors and cytokines and adhesion
      molecules in a number of cell types, including those of the human endometrium. In
      this study, we used immunocytochemistry to investigate the in vivo expression of
      the p50, IkappaBalpha and IkappaBbeta NFkappaB components in endometrium obtained
      from normal fertile women throughout the menstrual cycle. All three components
      were expressed by both the stromal and epithelial cells of the endometrium and
      staining was predominately seen in the cytoplasm of the cells. Staining for p50
      was more intense in the epithelial compartment than the stromal compartment.
      Staining in the stromal compartment was low to moderate throughout the cycle but,
      in the epithelial compartment, staining was cycle dependent and increased
      slightly during the mid-secretory phase. The staining patterns for IkappaBalpha
      and IkappaBbeta were similar. As for p50, staining for both proteins was greater
      in the epithelial compartment compared to the stromal compartment and stromal
      cell staining was low to moderate throughout the cycle. However, in contrast to
      p50, staining for the IkappaB proteins in epithelial cells decreased during the
      mid-secretory phase of the cycle. Although the immunocytochemistry technique used
      is only semi-quantitative, the results suggest an increased expression of the
      active and a decreased expression of the inhibitory NFkappaB components by the
      endometrium at the time of implantation. If confirmed, it would suggest that
      NFkappaB is involved in the control of factors important in the implantation
      process.

PMID- 11839393
TI  - Modulation of T-cell CD3-zeta chain expression during normal pregnancy.
AB  - The objectives of this study were to assess the modulation of T-cell CD3-zeta
      expression by factor(s) present in sera of pregnant women, to correlate this
      activity with markers of T-cell function associated with pregnancy, and to
      identify the presence of a circulating pregnancy-associated factor responsible
      for the suppression of CD3-zeta chain. The suppression of TcR/CD3-zeta expression
      on cultured T-lymphocytes (Jurkat cells) by sera and amniotic fluids from
      pregnant women was examined by Western immunoblots and quantitated by
      densitometry. This suppression was correlated with the induction of T-cell
      apoptosis and reduced production of IL-2. The serum component suppressing zeta
      expression was characterized by ultrafiltration and protease sensitivity.
      Incubation of Jurkat cells with sera obtained from women in the first trimester
      produced a slight, but not statistically significant, suppression of zeta
      expression; however, sera from pregnant women in the second and third trimesters
      and amniotic fluids significantly suppressed zeta levels in a dose-dependent
      manner. The loss of zeta chain correlated with both reduced secretion of IL-2 and
      induction of lymphocyte apoptosis. Fractionation of sera by ultrafiltration
      demonstrated that the zeta chain suppressive factor was <5 kDa, and its trypsin
      sensitivity suggests a proteinaceous moiety. Pregnancy is associated with a
      progressive suppression of cell-mediated immunity. These suppressed T-cell
      functions have been linked to Fas/Fas ligand-induced apoptosis and suppression of
      Th1 cytokines, including IL-2. We demonstrate that these pregnancy-associated
      events are mimicked by a factor(s) present in patient-derived fluids. Suppression
      of zeta expression appears to be due to a circulating low-molecular-weight
      protein that suppresses CD3-zeta in a concentration-dependent manner.

PMID- 11839394
TI  - A repertoire of cytokines in human seminal plasma.
AB  - The pathophysiological significance of seminal cytokines in sperm function is
      still controversial. We determined the repertoire of cytokines in seminal plasma
      obtained from men with or without abnormalities in semen and assessed the
      pathophysiological significance of seminal cytokines. After conventional analysis
      of semen samples obtained from 86 men, levels of seminal cytokines (interleukin
      [IL]-1alpha, IL-2, IL-4, IL-6, IL-8, tumor necrosis factor-alpha [TNF-alpha],
      interferon-gamma, granulocyte colony-stimulating factor [G-CSF], macrophage CFS
      [M-CSF]) and granulocyte elastase were measured by an enzyme-linked immunosorbent
      assay. Leukocytospermia was defined as seminal plasma, which has > or =1000 ng/ml
      granulocyte elastase. Leukocytospermia was found in nine of 62 of the subjects in
      the normozoospermic group but in none of the 24 subjects showing abnormal sperm
      parameters (azoospermia, n=5; oligozoospermia, n=4; asthenozoospermia, n=15). The
      IL-8 level in the leukocytospermic group was significantly higher than those in
      the normal and oligozoospermic groups. IL-1alpha and TNF-alpha levels in the
      leukocytospermic group were significantly higher than those in the normal and
      asthenozoospermic groups. Although the G-CSF level in the leukocytospermic group
      was significantly higher than that in the normal group, high levels of M-CSF were
      detected in all groups. The IL-8 level was strongly correlated with IL-1alpha
      (r=0.935, P<0.0001) and G-CSF (r=0.916, P<0.0001) levels. Cytokines detected in
      seminal plasma are associated with the pathogenesis of leukocytospermia but not
      with the pathogenesis of asthenozoospermia and oligozoospermia.

PMID- 11839396
TI  - Identification of post-vasectomy sperm auto-antigens in fox (Vulpes vulpes) by
      two-dimensional gel electrophoresis and Western blotting.
AB  - The aim of this work was to identify antigenic surface proteins on fox
      spermatozoa. Six foxes were inguitinally vasectomised, and the time course of
      antibody response in the sera was studied. Five out of the six foxes reacted to
      vasectomy with a production of antisperm antibodies. The number of bands
      recognised by Western blot was maximal 120-150 days after the vasectomy, at the
      end of the reproductive season. On the whole, 30 bands were recognised between 9
      and 150 kDa. The pattern of recognised proteins varied from one fox to another.
      The humoral response was studied in one fox 2 years after the vasectomy, before,
      during and after the breeding season. The same proteins were recognised, but the
      intensity of staining was increased during the testis regression. Using FITC
      labelling on sperm smears with fox sera, antigens were localised at or near the
      sperm surface, either on the acrosome or both on the acrosome and on the
      flagellum. Using two-dimensional gel electrophoresis and Western blotting, we
      identified eight areas containing major antigens, recognised by at least two
      sera. The molecular weights (kDa) and isoelectric points of the repeated antigens
      were, respectively [150, 6.6-6.0]; [105-98, 6.0-5.5]; [97, 4.6-4.3]; [95, 5.0];
      [85-80, 5.4-5.1]; [42, 5.0-4.8]; [17-15, 6.5-5.9]; and [17-15, 5.5-4.8]. The
      results of this study can be used to characterise more precisely fox sperm auto
      antigens by microsequencing the selected proteins.

PMID- 11839395
TI  - Evaluation of the proacrosin/acrosin system and its mechanism of activation in
      human sperm extracts.
AB  - Acrosin is an acrosomal protease synthesized as a proenzyme and activated into
      beta-acrosin during the acrosome reaction. In the present study, a set of
      sensitive assays was developed to identify the proacrosin/acrosin system and to
      evaluate its activation pattern in human sperm extracts. Immunocytochemical
      analysis with monoclonal antibody (Mab) AcrC5F10 showed specific staining on the
      acrosome of permeabilized ejaculated and capacitated spermatozoa. Acrosome
      reaction was associated with a decrease in staining. AcrC5F10 specifically
      recognized a 55-kDa band (proacrosin) in Western immunoblots. Activation studies
      showed enzymatically active intermediates of 39 and 35 kDa after zymography.
      Immunoreactive bands of 52, 43, 34, 21-26 and 16 kDa were identified in the
      activation patterns developed with AcrC5F10. Activation was completely inhibited
      in the presence of 9 mM CaCl(2) or 100 mM benzamidine. A multiple sequence
      alignment revealed partial conservation of putative cleavage sites in the
      proacrosin sequence. The tests described allow the detection of human proacrosin
      in spermatozoa and sperm protein extracts, as well as the evaluation of the
      proenzyme activation pattern. They can be used to study the effect of inhibitors
      upon proenzyme activation. In addition, alterations in proacrosin activation in
      semen samples with abnormal acrosin enzymatic activity can be analyzed using
      these assays.

PMID- 11839397
TI  - Effects on fertility of immunizing mice with anti-idiotypic antibodies to porcine
      zona pellucida antigen.
AB  - OBJECTIVE: To evaluate the effects on fertility by immunization with anti
      idiotypic antibodies to porcine zona pellucida (PZP) antigen. METHOD: Anti
      idiotypic antibodies (Ab(2)) were produced in New Zealand rabbits immunized with
      17D3 monoclonal antibodies (mAbs) (IgG, Ab(1)) to PZP antigen. The antisera were
      first passed through immuno-affinity chromatography column linked to normal mouse
      IgG so as to remove the antibody bound to normal mouse IgG The passing elute was
      then purified by immuno-affinity chromatography using 17D3 mAbs to get the Ab(2).
      Female BALB/c mice, 5-week-old, were grouped and immunized with the Ab(2), PZP
      antigen, target antigen of the Ab(1) and normal rabbit IgG, respectively. The
      treated female mice were mated with male BALB/c mice and sacrificed at gestation
      day 10. Analyses included ELISA measurement of anti-ZP antibody titer, fetal
      number determination and evaluation of ovarian histomorphology. RESULTS: The
      Ab(2) appeared as a single protein band by SDS-PAGE. Shown by a competitive
      inhibition ELISA, the Ab(2) specifically bound to the variable region of the 17D3
      Ab(1). Compared with controls, the female mice immunized with Ab(2) showed a
      decreased pregnancy rate and a statistically significant reduction in fetal
      numbers. Histological examination of ovaries demonstrated that Ab(2) exposure
      interfered less with follicular development than did exposure to PZP. CONCLUSION:
      Immunization of female mice with Ab(2) to PZP mAbs suppresses fertility and fetal
      numbers with minimal ovarian pathology.

PMID- 11839398
TI  - Immunological response of female macaques to the PH-20 sperm protein following
      injection of recombinant proteins or synthesized peptides.
AB  - Because of its location on the sperm surface and its multiple functions during
      fertilization, the PH-20 protein is a potential target for contraceptive
      vaccines. Cynomolgus macaques were immunized using four different adjuvants
      together with synthesized peptides or recombinant proteins representing selected
      regions of macaque PH-20. The synthesized peptide (amino acids 387-412,
      designated Peptide 4) was used as a linear molecule in a 1:1 ratio with a peptide
      sequence of tetanus toxoid, as well as a multiple antigenic peptide (MAP) matrix
      held together by scaffolding lysine residues. In the MAP construct, the ratio of
      Peptide 4 to tetanus peptide was 4:1. To circumvent the poor production of
      recombinant PH-20 in bacterial cells, two truncated forms of the molecule were
      expressed in Escherichia coli, G18 (encoding amino acids 143-510) and E10
      (encoding amino acids 291-510). The adjuvants were Montanide ISA 51, Titermax
      Gold, Syntex adjuvant formulation (SAF), and QS-21. All of the antigen/adjuvant
      combinations produced significant immune responses as measured by ELISA. The
      circulating antibodies from immunized animals recognized macaque sperm surface PH
      20 on Western blots and were shown by indirect immunofluorescence to bind to the
      surface of macaque sperm. Montanide and Titermax were associated with higher
      titers of anti-PH-20 antibodies than QS-21 and SAF adjuvants. Immunization with
      Titermax, however, resulted in sterile abscesses in 4 of 8 animals injected. We
      conclude that antigens derived from synthesized peptides and recombinant proteins
      representing selected regions of the PH-20 molecule can be used as vaccine
      components in combination with the adjuvant Montanide to elicit a significant
      sperm-directed antibody response in immunized macaques.

PMID- 11839400
TI  - Cytokine expression in peripheral blood lymphocytes indicates a switch to
      T(HELPER) cells in patients with preeclampsia.
AB  - We sought to determine whether cytokine expression in peripheral blood
      mononuclear cells is altered in patients with preeclampsia and in patients with a
      history of recurrent spontaneous abortion (RSA). Twenty-four patients with
      preeclampsia and twenty patients with a history of RSA were included into the
      study. Two control groups consisted of twenty healthy pregnant and twenty healthy
      non-pregnant women. The intracellular expression of interleukin-2 (IL-2),
      interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) were determined in
      peripheral blood mononuclear cells (PBMCs) by flow cytometry as a measure of
      cytokine production. IL-2 synthesis was significantly elevated in the third
      trimester in preeclamptic patients in comparison with the control group. Non
      pregnant women with RSA showed a significantly lower expression of IFN-gamma
      compared to the non-pregnant control group. Our data suggest an abnormal immune
      response in preeclamptic patients characterised by a shift to a predominantly Th1
      type immunity.

PMID- 11839399
TI  - Oral contraceptive use induces upregulation of the CCR5 chemokine receptor on
      CD4(+) T cells in the cervical epithelium of healthy women.
AB  - Heterosexual transmission of human immunodeficiency virus type I (HIV-1) is the
      predominant mode of infection worldwide. Increased risk of HIV-1 transmission has
      been reported with oral contraceptive use. To elucidate the underlying mechanism
      of this observation, intraepithelial endocervical T lymphocytes from women using
      oral contraceptives were analysed for expression of activation and chemokine
      receptors. T lymphocytes from the cervical epithelium and peripheral blood of
      women using combined oral contraceptives (COC) and those using no contraceptive
      method (NONE) were compared. Cervical T lymphocytes were obtained with a
      cytobrush and in parallel, mononuclear leukocytes were separated from blood by
      centrifugation over a ficoll-hypaque gradient. Cellular activation markers and
      HIV-1 chemokine co-receptors, CXCR4 and CCR5, were analysed by flow cytometry.
      Activation markers (CD69, CD25 and HLA-DR) on T cells were expressed at higher
      levels in the cervical epithelium than peripheral blood T cells but were no
      different in those women using COC. CXCR4 was widely expressed on cervical and on
      blood T cells, but was not influenced by COC use. By contrast, the number of T
      cells expressing CCR5 increased in women using COC (P<0.05). The level of
      cervical CCR5 expression per cell was shown to increase on both activated CD4(+)
      (CD69(+), P<0.05; HLA-DR(+), P<0.01) and CD8(+) (CD69(+), P<0.05; HLA-DR(+),
      P<0.05) T lymphocytes compared with COC use. These data show that with COC use,
      the expression of CCR5 on CD4(+) T lymphocytes is increased. Furthermore, the
      cell surface density of CCR5 is increased on both CD4(+) and CD8(+) T lymphocyte
      subsets. These findings suggest a mechanism by which oral contraceptive use can
      increase the risk of HIV-1 transmission.

PMID- 11839403
TI  - Enhancement of contrast regions in suboptimal ultrasound images with application
      to echocardiography.
AB  - In this paper we propose a novel feature-based contrast enhancement approach to
      enhance the quality of noisy ultrasound (US) images. Our approach uses a phase
      based feature detection algorithm, followed by sparse surface interpolation and
      subsequent nonlinear postprocessing. We first exploited the intensity-invariant
      property of phase-based acoustic feature detection to select a set of relevant
      image features in the data. Then, an approximation to the low-frequency
      components of the sparse set of selected features was obtained using a fast
      surface interpolation algorithm. Finally, a nonlinear postprocessing step was
      applied. Results of applying the method to echocardiographic sequences (2-D + T)
      are presented. The results demonstrate that the method can successfully enhance
      the intensity of the interesting features in the image. Better balanced
      contrasted images are obtained, which is important and useful both for manual
      processing and assessment by a clinician, and for computer analysis of the
      sequence. An evaluation protocol is proposed in the case of echocardiographic
      data and quantitative results are presented. We show that the correction is
      consistent over time and does not introduce any temporal artefacts.

PMID- 11839404
TI  - Changes of tumor vascularity during gene therapy monitored with color Doppler US.
AB  - Using contrast-enhanced color Doppler (CD) sonography, we assessed alterations of
      tumor blood flow induced in 25 murine Morris hepatomas transfected with a
      gancyclovir- (GCV-)sensitizing Herpes simplex virus thymidine kinase (HSVtk)
      suicide gene in combination with systemic GCV treatment and compared findings
      with a control tumor. CD measurements were quantified by the color pixel density
      (CPD) and the mean encoded flow velocity (mean color value, MCV), using computer
      assisted image analysis, and compared with histologic arteriole counts. During 5
      days, the tumor volume remained constant. In HSVtk-expressing tumors, the median
      CPD dropped from 16% at baseline to 5% on day 5 (p = 0.001), remaining constant
      in controls. The MCV decreased from 1.9 cm/s to 1.6 cm/s in the HSVtk-expressing
      tumors (p = 0.001) and rose from 1.8 cm/s to 2.0 cm/s in the controls (p =
      0.002). In an accompanying histologic arteriole assay, we found no alterations
      attributable to treatment.

PMID- 11839405
TI  - Discriminative ability of conventional echocardiography and tissue Doppler
      imaging techniques for the detection of subclinical cardiotoxic effects of
      treatment with anthracyclines.
AB  - This study investigated improvement of diagnosing myocardial damage caused by
      anthracyclines using tissue Doppler imaging (TDI). The optimal set of
      conventional echocardiographic and/or TDI parameters, needed for the
      discrimination of survivors from healthy controls, was retrospectively assessed.
      A total of 60 patients and 99 controls, age range 8.5 to 17.6 years, were
      studied. The survivors received 50 to 400 mg/m(2) cumulative dose of
      anthracyclines, with a mean follow-up of 7.3 (+/-2.3) years. The parameters used
      in the discriminant score (S-score) were selected from a large set of 51
      echocardiographic parameters, using logistic regression analysis (stepwise
      selection). The correct classification probability (C-index) and the generalized
      distance (d) between the distributions of S-scores were used to measure the
      overall discriminative performance of each echocardiographic technique separately
      and in combination. The overall discriminative performance of the conventional
      echo-Doppler parameters (C = 77.3%, d = 1.04) was lower than that of the TDI (C =
      84.2%, d = 1.37); the highest C-index was obtained using both techniques (C =
      89.2%, d = 1.66). The set of parameters includes: LV fractional shortening and MV
      early diastolic flow velocity, two long-axis and five apical 4-CV TDI wall
      velocities (systolic and diastolic). In the patient group, the S-score was
      positively associated with cumulative dose of anthracyclines (p = 0.05) and
      duration of treatment (p = 0.01). The diagnostic index S-score, based on a
      limited number of variables from both techniques simultaneously, could
      retrospectively discriminate asymptomatic children with anthracycline-induced
      cardiomyopathy from healthy controls. The potentials of the S-score for serial
      and prospective studies are further investigated.

PMID- 11839406
TI  - Respiratory motion compensation for 3-D freehand echocardiography.
AB  - Motion of the diaphragm during respiration causes a displacement of the heart
      relative to the position of a transthoracic ultrasound (US) probe. These
      respiration-induced shifts of cardiac position can lead to spatial misalignments
      of data when reconstructed in 3-D. We show how to compensate for this motion
      using a technique that extends the tracking of the probe to additionally monitor
      a marker placed on the patient umbilicus. The motion of the umbilicus is
      calibrated to that of the diaphragm using one additional scan. This calibration
      is used to correct the 3-D spatial positions of cardiac images acquired from
      multiple acoustic views. At both systole and diastole, segmentations of the
      endocardial border visually appear more consistent after our correction than with
      no correction. Long and short axis segmentations should intersect on the
      endocardium. After correction, their separation at the closest point is shown to
      be reduced.

PMID- 11839407
TI  - Automatic evaluation of arterial diameter variation from vascular echographic
      images.
AB  - An automatic procedure for accurate arterial diameter evaluation from B-mode
      images obtained by diagnostic ultrasound systems is presented. It is used for
      measuring brachial artery dilation following reactive hyperemia induced by
      forearm ischemia, which is an appropriate parameter to study endothelial function
      in humans. B-mode images obtained from the diagnostic ultrasound system are
      acquired on a personal computer as grey intensity fields (pixels). A completely
      automatic algorithm is then applied and the artery walls are identified by two
      discrete sets of points. Artery diameter is evaluated by parabolic least-square
      approximation. The accuracy and extensive range of applicability of the diameter
      evaluation procedure were demonstrated both by preliminary analytic test cases
      and in vivo analyses. Reproducibility of the diameter estimate was assessed by in
      vivo measurements. The proposed procedure permits fast and accurate analysis of
      large amounts of data, because it requires no action by the operator. It thus
      represents a valuable tool for assessment of endothelium-dependent vasodilation,
      especially in large, multicentric clinical trials.

PMID- 11839408
TI  - Axial strain imaging of intravascular data: results on polyvinyl alcohol cryogel
      phantoms and carotid artery.
AB  - Mapping the local elastic properties of an atherosclerotic artery is of major
      interest for predicting the disease evolution or an intervention outcome. These
      properties can be investigated by elastography, which estimates the strain
      distribution within a medium in response to a stress. But because diseased
      arteries are highly heterogeneous, a small global deformation may result in high
      local strains in the softest regions. For those reasons, we use in this paper the
      strain estimation method we recently developed to compute elastograms of original
      vessel-mimicking cryogel phantoms and a fresh excised human carotid artery. This
      adaptive method has been effectively proved to be accurate in a wider range of
      strains (0-7%) than commonly used gradient-based methods, and very adapted for
      investigating highly heterogeneous tissues. Resulting elastograms cover a wider
      range of strains (0-3.5%) than all previously reported intravascular elastograms,
      improving the discrimination between healthy and diseased regions.

PMID- 11839409
TI  - Transmural variation of myocardial attenuation measured with a clinical imager.
AB  - The objective of this study was to quantify the transmural variation in
      attenuation for the septal and lateral walls of the heart. Our approach was to
      utilize a commercially available ultrasonic imaging system to acquire images of
      excised sections of eight sheep hearts with an orientation similar to that
      encountered in the apical four-chamber view. The measured values (mean +/-SE) of
      the slope of attenuation for the transmural regions of the septum are: 1.40 +/
      0.11, 0.99 +/-0.09, and 1.85 +/-0.16 (dB/cm/MHz) for the left subendocardial,
      midmyocardial, and right subendocardial zones, respectively. The analogous data
      from the lateral wall are: 1.42 +/-0.11, 0.83 +/-0.07, and 1.20 +/- 0.16
      (dB/cm/MHz) for the subendocardial, midmyocardial, and subepicardial zones,
      respectively. These data demonstrate that ultrasonic attenuation associated with
      the septum and the lateral wall, when imaged in a manner similar to that of the
      apical four-chamber view, is anisotropic.

PMID- 11839410
TI  - A dual-snake model of high penetrability for ultrasound image boundary
      extraction.
AB  - Most deformable models require the initial contour to be placed close to the
      boundary of the object of interest for boundary extraction of ultrasound (US)
      images, which is impractical in many clinical applications. To allow a distant
      initial contour, a new dual-snake model promising high penetrability through the
      interference of the noises is proposed in this paper. The proposed dual-snake
      model features a new far-reaching external force, called the discrete gradient
      flow, a connected component-weighted image force, and an effective stability
      evaluation of two underlying snakes. The experimental results show that, with a
      distant initial contour, the mean distance from the derived boundary to the
      desired boundary is less than 1.4 pixels, and most snake elements are within 2.7
      pixels of the desired boundaries for the synthetic images with CNR > or =1. For
      the clinical US images, the mean distance is less than 1.9 pixels, and most snake
      elements are within 3 pixels of the desired boundaries.

PMID- 11839411
TI  - Improved method for determining resolution zones in ultrasound phantoms with
      spherical simulated lesions.
AB  - Quantification of ultrasound (US) imager performance simulating human observers
      is addressed using size-dependent lesion signal-to-noise ratio (LSNR) analysis of
      images of spherical simulated lesions in phantoms. LSNR values obtained over a
      broad range of image depths can be used with a single detectability threshold to
      determine the depth range over which lesions of a given size and contrast are
      deemed to be detectable, yielding a performance metric. Optimal LSNR analysis
      requires a priori knowledge of lesion locations in the image so that LSNR values
      relate to the center of each lesion. Phantoms having a regular array of
      accurately positioned spherical simulated lesions are described, along with
      easily employed and robust software that accurately determines lesion locations
      in images, even when only a few are detectable by visual inspection. The software
      accounts for image spatial calibration inaccuracies and accommodates sector,
      curvilinear, etc., formats. The minimum number of equivalent lesions to yield an
      acceptable mean (counteracting speckle variations) also is addressed.

PMID- 11839412
TI  - Experimental corroboration of the nonstationary strain estimation errors in
      elastography.
AB  - The nonstationary variation in the noise performance of the cross-correlation
      based strain estimator due to frequency-dependent attenuation and lateral and
      elevational signal decorrelation have been addressed theoretically in recent
      papers using the strain-filter approach. In this paper, we present the
      experimental verification and corroboration of the nonstationary effects on the
      strain estimation results. The accuracy and precision of the strain estimate
      deteriorates with lateral position in the elastogram, due to the lateral motion
      of tissue scatterers, and with depth, due to frequency-dependent attenuation. The
      results illustrate that the best strain-estimation noise performance is obtained
      in the focal zone of the transducer and around the axis of symmetry of the
      phantom.

PMID- 11839413
TI  - Transcranial ultrasound-improved thrombolysis: diagnostic vs. therapeutic
      ultrasound.
AB  - Success of stroke treatment with rt-PA depends on rapid vessel recanalization.
      Enzymatic thrombolysis may be enhanced by additional transcranial application of
      ultrasound (US). We investigated this novel technique using a 185-kHz probe and
      compared it to standard diagnostic US. In vitro studies were performed in a
      continuous pressure tubing system. Clots were placed in a postmortem skull and
      treated with rt-PA together with or without transtemporal 185-kHz US insonation
      (2W/cm(2)) and in comparison to 1-MHz diagnostic US (0.5 W/cm(2)). Recanalization
      time was significantly (p < 0.01) shorter in the 185-kHz (14.1 min) and 1-MHz
      (17.1 min) US rt-PA treatment group compared to rt-PA treatment alone (29.3
      min.). Flow rate was significantly higher (p < 0.025) and increased faster in the
      combined treatment group with rt-PA + 185-kHz US compared to rt-PA + 1-MHz US. We
      investigated the blood-brain barrier in rats after 90-min exposure time of the
      brain with 185-kHz US, but no damage was observed. Results suggest efficacy and
      safety of the 185-kHz transducer, which is superior to diagnostic US. Such a
      novel US probe may be able to optimize thrombolytic stroke treatment.

PMID- 11839415
TI  - A computerised quality control testing system for B-mode ultrasound.
AB  - Current methods of ultrasound (US) imaging quality control involve an observer
      taking a series of measurements on test object images. This process is very
      labour-intensive, rapidly becoming more so as the complexity of US scanners
      increases. Also, many of the measurements are based on the subjective judgement
      of the operator and are, therefore, prone to an undesirable level of
      intraobserver and interobserver variation. We have developed a suite of programs
      to analyse captured US images to estimate a number of performance parameters,
      including resolution, high- and low-contrast penetration depths and high- and low
      contrast sensitivity. In this system, images of the ATS Laboratories Multipurpose
      Phantom Model 539 are acquired on a PC with a video capture card, and analysed
      using the software developed. Automated tests have been developed for resolution,
      low- and high-contrast penetration and low- and high-contrast sensitivity. A
      preliminary validation of the system was carried out using images from two
      curvilinear probes and a linear-array probe operating at 5 MHz, 7.5 MHz and 10
      MHz, respectively. The 95% confidence intervals ranged from +/- 17% to +/- 21%
      for resolution measurements and from 0% to +/- 1.5% for low-contrast penetration.
      The system provides an index of visibility for high- and low-contrast targets, as
      compared to the coarse visual assessment of a human observer, with 95% confidence
      intervals ranging from +/- 6% to +/- 13% for low-contrast sensitivity and from +/
      3% to +/- 25% for high-contrast sensitivity. Advantages of the system over the
      human observer include improved reproducibility and increased information
      regarding visibility of targets. A more detailed multicentre validation is
      currently being undertaken.

PMID- 11839414
TI  - The effect of therapeutic ultrasound on repair of the achilles tendon (tendo
      calcaneus) of the rat.
AB  - The purpose of this study was to evaluate the effects of therapeutic ultrasound
      (US) on the healing process in the Achilles tendon (Tendo calcaneus) of Wistar
      rats after tenotomy. Sonication was performed at a frequency of 1 MHz, an
      intensity of 0.5 W/cm(2) (SATA), for 5 min, over a period of 14 consecutive days
      in two modalities (n = 15); in both continuous and pulsed modes. The control
      group was divided into tenotomized, mock-sonicated and nontenotomized tendons (n
      = 15). On the 15th postoperative day, the tendons were removed and analyzed by
      using the polarized light microscopy, with the purpose of detecting and measuring
      the organization of collagen fibers through birefringence. The results showed a
      high birefringence for the tendons treated using the pulsed mode (p < 0.001),
      revealing the best organization and aggregation of collagen bundles. Sonication
      in the continuous mode induced a decrease (p = 0.047) in the ability to quicken
      the healing process. These findings suggest that US therapy is beneficial in the
      early healing process of tendons when the pulsed mode is used.

PMID- 11839416
TI  - Tissue-mimicking materials for teaching sonographers and evaluation of their
      specifications after three years.
AB  - In this paper, an algorithm is introduced for making breast phantoms and abnormal
      masses (cyst, fibroadenoma and cancer). The evaluation of ultrasonic properties
      (sound velocity and amplitude attenuation coefficient) of these normal breast
      phantoms and abnormal masses and their ultrasonic images shows that they are
      stable over 3 years. The measurement and evaluation results of ultrasonic images
      of our phantoms show that they behave like human breast tissues. Practicing with
      these phantoms for developing fine-needle aspiration (FNA) skills in sonographers
      shows that these phantoms reduce the time required for successful FNA. The
      ultrasonic phantoms have different ultrasonic applications, including ultrasonic
      medical imaging, the quality control of ultrasound (US) instruments, processing
      technique evaluation and US training; moreover, they are stable in room
      temperature and can keep their specifications for more than 3 years.

PMID- 11839418
TI  - Cognitive modulation of pain: how do attention and emotion influence pain
      processing?

PMID- 11839419
TI  - Spatial summation for pain perception: interaction of inhibitory and excitatory
      mechanisms.
AB  - To study the relation between size of the surface stimulated and perceived pain
      intensity (spatial summation effect), subjects sequentially immersed
      predetermined segments of the surface of their arm, between the fingertips and
      the shoulder, in circulating nociceptive hot water. Immersion sessions were of
      three types: (i) increasing session (immersion beginning at fingertips and
      increasing to shoulder); (ii) decreasing session (immersion beginning at shoulder
      and decreasing to fingertips); and (iii) whole arm+increasing session
      (preliminary immersion of the whole arm up to shoulder, followed by an increasing
      session from fingertips to shoulder). Results showed a positive spatial summation
      effect (pain perception positively correlated to the size of the surface
      stimulated) during both the decreasing session and the whole arm+increasing
      session. However, no spatial summation effect was found during the increasing
      session (fingertips to shoulder). In addition, pain perceived for a surface area
      was less intense during the decreasing session compared to the increasing
      session. One possible explanation for the lack of a spatial summation effect
      during the increasing session is that inhibitory mechanisms are gradually
      recruited at the same time as excitatory afferences, thus 'cancelling out' any
      measurable spatial summation effect. The results obtained during the decreasing
      session and the whole arm+increasing session may be explained by inhibitory
      mechanisms being fully recruited at the beginning of the session with the
      immersion of the largest surface area (whole arm). The results are a shift of the
      pain perception curve and a positive relation between the surface stimulated and
      pain perception.

PMID- 11839420
TI  - The effects of excessive heat on heat-activated membrane currents in cultured
      dorsal root ganglia neurons from neonatal rat.
AB  - The effects of high temperature (53-61 degrees C) on membrane currents (I(heat))
      or depolarization (V(heat)) induced by noxious heat were studied in cultured
      dorsal root ganglia neurons from neonatal rats using the whole cell patch clamp
      technique. I(heat) or V(heat) produced by 3 s ramps of increasing temperature
      between 43 and 50 degrees C exhibited a fast slope (Q10>10) that was similar both
      during rising and falling temperature (n=85). Temperatures exceeding 52 degrees C
      resulted in slowdown in the recovery of I(heat), and the threshold for inducing
      I(heat) was shifted to lower temperatures in successive trials. These high
      temperatures (54-60 degrees C) caused a linear and incomplete recovery of I(heat)
      (Q10 decreased to <5; 4.5 +/- 0.4; n=17) and in successive trials the threshold
      of I(heat) decreased to temperatures close to that in the bath. The neurons,
      however, remained sensitive to capsaicin and to decreased extracellular pH. It is
      suggested that exposure of nociceptive neurons to excessive noxious heat results
      in an irreversible decrease of the energy barrier between the resting and
      activated state of the protein structures responsible for generation of I(heat).
      This may explain the sensitization of nociceptors after heat injury.

PMID- 11839421
TI  - Therapeutic administration of nitric oxide synthase inhibitors reverses
      hyperalgesia but not inflammation in a rat model of polyarthritis.
AB  - Nitric oxide (NO) has been postulated to play a role in pain as well as in
      inflammation. In the present studies, the effects of NO synthase (NOS) inhibitors
      on both pain and inflammation were examined in a rat model of polyarthritis.
      Female Lewis rats were injected intraperitoneally (i.p.) with
      peptidoglycan/polysaccharide (PG/PS) or saline to induce arthritis. Hind paw
      volume, response latency to thermal nociceptive stimulus and mechanical threshold
      were measured daily for the next 35 days. Paw inflammation, thermal hyperalgesia
      and mechanical allodynia developed in all rats that received PG/PS compared to
      saline. On day 19 (chronic inflammation phase), rats were given either N(G)-nitro
      L-arginine methyl ester (L-NAME, non-selective NOS inhibitor, 100 mg/l), L-N (6)
      (1-iminoethyl) lysine (L-NIL, selective inducible NOS inhibitor, 10 mg/l) or no
      drug in drinking water. By day 21, L-NAME treatment reversed the thermal
      hyperalgesia completely and this effect remained until day 35. Similarly, L-NIL
      treatment reversed thermal hyperalgesia from days 24 to 34. Neither treatment
      affected mechanical allodynia. Paw volume was not different between PG/PS treated
      and PG/PS plus L-NAME treated rats. However, the PG/PS plus L-NIL treatment
      produced an increase in paw volume greater than did PG/PS alone. Other rats were
      treated with PG/PS plus the antiinflammatory agent indomethacin (days 19-35).
      Indomethacin treatment reversed all the measured parameters, although the
      reversal of mechanical allodynia was only partial. These results suggest that NO
      is involved in thermal, but not mechanical sensory pathways and that the
      selective inhibition of inducible NOS activity exacerbates established
      inflammation.

PMID- 11839422
TI  - Induction of Fos protein-like immunoreactivity in the trigeminal spinal nucleus
      caudalis and upper cervical cord following noxious and non-noxious mechanical
      stimulation of the whisker pad of the rat with an inferior alveolar nerve
      transection.
AB  - After transection of the inferior alveolar nerve (IAN: the third branch of the
      trigeminal nerve), the whisker pad area, which is innervated by the second branch
      of the trigeminal nerve, showed hypersensitivity to mechanical stimulation. Two
      days after IAN transection, the threshold intensity for escape behavior to
      mechanical stimulation of the ipsilateral whisker pad area was less than 1.0 g, a
      sign of allodynia, and returned to the preoperative level (preoperative
      threshold: 52.0 g) at 32 days after surgery. This decrement of escape threshold
      lasted for more than 3 weeks. The whisker pad area contralateral to the IAN
      transection also showed a decrease in escape threshold to non-noxious mechanical
      stimulation as compared with sham-operated rats. However, the change in threshold
      intensity for the side contralateral to transection was not as pronounced as that
      on the ipsilateral side. Fos protein-like immunoreactive (LI) cells were observed
      in the superficial laminae but not dominant in deeper laminae of the trigeminal
      spinal nucleus caudalis (Vc) and the first segment of the spinal cord (C1) after
      non-noxious mechanical stimulation of the whisker pad area in the rats with IAN
      transection. Fos protein-LI cells were expressed bilaterally in the Vc and C1,
      but were more numerous on the ipsilateral side to transection than on the
      contralateral side. The largest number of Fos protein-LI cells was observed at
      2400 microm caudal from the trigeminal subnucleus interporalis (Vi)-Vc border
      both in ipsilateral and contralateral sides. The number of Fos protein-LI cells
      increased after application of 1, 4, and 16 g stimuli as compared to rats without
      mechanical stimulation. Furthermore, an extensively greater number of Fos protein
      LI cells were expressed both in superficial and deep laminae of the bilateral Vc
      and C1 of the spinal cord after subcutaneous injection of mustard oil into the
      whisker pad. Fos protein expression after mustard oil injection was much stronger
      than that observed after any mechanical stimulation in the rats with IAN
      transection. These data suggest that the change in the numbers and spatial
      arrangement of nociceptive neurons in the Vc and C1 after IAN transection reflect
      the development of mechanical hyperalgesia in the area adjacent to the IAN
      innervated region.

PMID- 11839423
TI  - A comparison of chronic pain behavior following local application of tumor
      necrosis factor alpha to the normal and mechanically compressed lumbar ganglia in
      the rat.
AB  - To study the role of inflammatory cytokines in the initiation and persistence of
      radiculopathy as seen in humans, tumor necrosis factor alpha (TNF-alpha) was
      administered either to normal, uninjured L5 dorsal root ganglia (DRG) of rats via
      a hole drilled through the transverse process, or to chronically compressed L5
      DRG via a hollow stainless steel rod inserted into the intervertebral foramen. In
      other experiments, a mixture of soluble TNF receptors (sTNF-Rs: sTNF-RIplus
      minussTNF-RII) was locally delivered to the chronically or acutely compressed DRG
      to neutralize the activity of endogenous TNF-alpha. Behavioral tests of
      mechanical allodynia were performed before and after TNF-alpha administration.
      Infusion of the normal DRG with TNF-alpha at a rate of 1 microl/h for 7 days
      induced ipsilateral mechanical allodynia (i.e. decreased mechanical withdrawal
      threshold) that lasted about 2 weeks. Infusion of the compressed DRG did not
      alter compression-induced allodynia within the first operative week but
      substantially enhanced the ipsilateral allodynia after the first postoperative
      week. Neutralizing the activity of endogenous TNF-alpha of the compressed DRG
      with sTNF-Rs reduced allodynia for 3 days, but was subsequently without effect.
      Similar results were obtained when sTNF-Rs were chronically administrated at the
      acutely compressed ganglion. Results demonstrated that exogenous TNF-alpha causes
      pain and mechanical allodynia when deposited at the normal DRG, and further
      enhances the ongoing allodynia when administrated at the compressed DRG. Results
      also suggest that endogenous TNF-alpha contributes to the early development of
      mechanical allodynia in rats with chronic DRG compression.

PMID- 11839424
TI  - Influence of endometriosis on pain behaviors and muscle hyperalgesia induced by a
      ureteral calculosis in female rats.
AB  - Endometriosis and urinary calculosis can co-occur. Clinical studies have shown
      that both painful and non-painful endometriosis in women are associated with
      enhanced pain and referred muscle hyperalgesia from urinary calculosis, but the
      mechanisms underlying this phenomenon are still poorly understood. The aim of
      this study was to develop an animal model adequate to explore this viscero
      visceral interaction in standardized conditions. Using a model of endometriosis
      previously developed to study reduced fertility and vaginal hyperalgesia,
      endometriosis (endo) or sham-endometriosis (sham-endo) was induced in rats by
      autotransplantation of small pieces of uterus (or, for sham-endo, fat) on cascade
      mesenteric arteries, ovary, and abdominal wall. After the endometrial, but not
      the fat autografts had produced fluid-filled cysts (3 weeks), urinary calculosis
      was induced by implanting an artificial stone into one ureter. Pain behaviors
      were monitored by continuous 24-h videotape recordings before and after stone
      implantation. Referred muscle hyperalgesia was assessed by measuring vocalization
      thresholds to electrical stimulation of the oblique musculature (L1 dermatome).
      The data were compared with previously reported data from rats that had received
      only the stone. Neither endo nor sham-endo alone induced pain behaviors.
      Following stone implantation, in endo rats compared to sham-endo and stone-only
      rats, pain behaviors specifically associated with urinary calculosis were
      significantly increased and new pain behaviors specifically associated with
      uterine pathology became evident. Muscle hyperalgesia was also significantly
      increased. To explore the relationship between the amount of endometriosis and
      that of ureteral pain behavior, two separate groups of endo rats were treated
      with either a standard non-steroidal anti-inflammatory drugs (ketoprofen) or
      placebo from the 12th to the 18th day after endometriosis induction. The stone
      was implanted on the 21st day. Ketoprofen treatment compared to placebo
      significantly reduced the size of the cysts and both ureteral and uterine pain
      behaviors post-stone implantation. The size of the cysts showed a significant
      linear correlation with the post-stone ureteral pain behaviors. In conclusion,
      endo increased pain crises and muscle hyperalgesia typically induced by a
      ureteral calculosis, and the ureteral calculosis revealed additional pain
      behaviors typically induced by uterine pathophysiology; and this enhancement was
      a function of the degree of endometriosis. This result closely reproduces the
      condition observed in humans and could be due to a phenomenon of 'viscero
      visceral' hyperalgesia, in which increased input from the cyst implantation sites
      to common spinal cord segments (T10-L1) facilitates the central effect of input
      from the urinary tract.

PMID- 11839425
TI  - Long-term cohort study comparing medical (oxcarbazepine) and surgical management
      of intractable trigeminal neuralgia.
AB  - Trigeminal neuralgia is a recurrent severe shooting neuropathic pain which can be
      managed both pharmacologically and surgically. However, there are no prospective
      data that compare these two therapeutic strategies. This study therefore aimed to
      assess long-term outcome in patients with intractable trigeminal neuralgia
      treated with oxcarbazepine and later with surgery. Fifteen patients (11 females)
      with trigeminal neuralgia intractable to available drugs (carbamazepine,
      phenytoin and baclofen), were prospectively followed for 13 years (1986-1999)
      with a total follow up time from onset of disease of 16 +/- 6 years (mean +/-
      SD), range 8-30 years. All patients were contacted in 1999 and 12 replied, two
      had died and one had last replied in 1996. Patients were first treated with
      oxcarbazepine 1200 +/- 600 mg daily dosage (mean +/- SD) and subsequently with
      surgery of their choice. The outcome measures used were: McGill Pain
      Questionnaire, Hospital Anxiety and Depression Scale, patient satisfaction
      questionnaire and clinicians' global evaluation. Pain control was initially
      achieved in all patients and oxcarbazepine was used continuously or
      intermittently for 4.0 +/- 3 years (mean +/- SD). Thirteen patients experienced
      some mild side effects and a dose-dependent hyponatraemia was noted.
      Subsequently, 12 patients required surgery (five microvascular decompressions and
      seven surgery at the level of the Gasserian ganglion) to control their pain and
      were followed up for 4.3 +/- 1.7 years post surgery (mean +/- SD). Three patients
      required repeat surgery to control their pain, which was successful in two. A
      further two patients continued with low dose medication post initially successful
      surgery. Three patients reported numbness and one hearing loss after surgery.
      Kaplan Meier analysis 3 years after oxcarbazepine use and then 3 years after
      surgery showed that the mean time for recurrence of pain after oxcarbazepine
      treatment was 10 months whilst for surgery it was 28 months (P<0.0001). Pain free
      periods and types of complications post surgery varied and depended on the type
      of surgery performed. Due to the small numbers, it was not possible to analyse
      the different types of surgical procedures individually. Outcomes after any type
      of surgery were better on all evaluations and eight patients felt that they
      should have had surgery earlier. Oxcarbazepine is a potent antineuralgic drug
      with very good acceptability and tolerability. However, its effectiveness was
      rather short term necessitating surgical intervention. As surgery was associated
      with better outcome, patients may therefore benefit from having surgery earlier
      rather than later in the disease process in order to improve quality of life,
      freedom from medication and the need for regular follow up. Surgery does not
      provide pain relief for all patients. This is the first study that has compared
      outcome in a group of patients who have had both pharmacological and surgical
      treatments. As these data cannot be extrapolated to other antineuralgic drugs,
      similar comparative studies would be appropriate.

PMID- 11839426
TI  - The impact of pain and symptoms of depression in scleroderma.
AB  - Systemic sclerosis (scleroderma) is a rare connective tissue disease that can
      affect multiple organ systems. Case reports and small treatment studies suggest
      that pain is significant in scleroderma, but few data speak of the frequency or
      impact of pain. This study sought to determine the frequency and impact of pain,
      symptoms of depression, and social network characteristics on physical
      functioning and social adjustment in patients with scleroderma. One hundred and
      forty-two scleroderma patients completed measures of pain, depressive symptoms,
      social network characteristics, physical functioning, and social adjustment.
      Sixty-three percent reported at least mild pain and 50% reported at least mild
      levels of depressive symptomatology. Hierarchical regression analyses revealed
      that pain, depressive symptoms, and employment status (disabled/unemployed vs.
      not) were significant, independent predictors of physical functioning, together
      accounting for 37% of the total variance. Pain was the single strongest predictor
      of physical function, accounting for 20% of the variance. Depressive symptoms,
      physical functioning, diversity of social network, and employment status were
      significant independent predictors of social adjustment, together accounting for
      63% of the variance. Depressive symptoms were the single strongest predictor of
      social adjustment, accounting for 26% of the variance. The effects of pain and
      physical function on social adjustment became non-significant when depressive
      symptoms were entered into the model, suggesting that symptoms of depression
      mediate the effect of pain and physical function on social adjustment. These
      findings indicate that pain is common in scleroderma and that pain and depressive
      symptoms are significant determinants of physical functioning and social
      adjustment, two important components of health-related quality of life. Increased
      attention to effective management of pain and symptoms of depression in
      scleroderma will likely lead to improved functioning and quality of life.

PMID- 11839427
TI  - Attenuation of hyperalgesia in a rat model of neuropathic pain after intrathecal
      pre- or post-treatment with a neurokinin-1 antagonist.
AB  - Although many studies have demonstrated a role for substance P in pain, there
      have been conflicting reports implicating the involvement of substance P in
      neuropathic pain models. In this study, the non-peptide neurokinin-1 (NK-1)
      receptor antagonist, L-732,138 was chronically administered by intrathecal (i.t.)
      injection to rats with mono-neuropathy produced by sciatic nerve constriction.
      Rats exhibited tactile allodynia and cold hyperalgesia over a 16-day testing
      period. L-732,138 (5-200 nmol) administered i.t. prior to and for 3 consecutive
      days post-surgery attenuated the mechanical allodynia and cold hyperalgesia on
      days 4 and 8 post-surgery. The effects of i.t. L-732,138 were also determined in
      rats with established nerve injury-induced neuropathy. The NK-1 receptor
      antagonist was injected for 4 consecutive days starting on day 8 post-sciatic
      nerve injury. Administration of L-732,138 (5-200 nmol) i.t. produced both anti
      allodynic and anti-hyperalgesic effects on day 12, but the effect was not
      permanent, as nociceptive thresholds were similar to controls by day 16. These
      results demonstrate that substance P is involved both in the induction and the
      maintenance of neuropathic pain and provides justification for the development
      and administration of substance P antagonists for the management of clinical
      neuropathic pain.

PMID- 11839428
TI  - Mechanisms of opioid-induced pain and antinociceptive tolerance: signal
      transduction.

PMID- 11839429
TI  - In response to treatment of central post-stroke pain with oral ketamine by Pamela
      G. Vick and Tim J. Lamer.

PMID- 11839430
TI  - Central antinociceptive-analgesic effect of diclofenac.

PMID- 11839434
TI  - Solid state characterization of an neuromuscular blocking agent--GW280430A.
AB  - GW280430A is an ultrashort-acting neuromuscular blocking agent and is targeted
      for muscle relaxation as part of the intubation surgical procedure. The objective
      of this work was to perform solid state characterization on GW280430A and to
      evaluate the relationship between water content and glass transition temperature
      (Tg). GW280430A was characterized by differential scanning calorimetry,
      thermogravimetric analysis, powder X-ray diffraction (PXRD), microscopy and
      moisture sorption. The effect of water content on the Tg of GW280430A was
      evaluated by equilibrating the material over saturated salt solutions at a range
      of relative humidities (6.4-72.6%) and determining the Tg by DSC using
      hermetically sealed aluminum pans. GW280430A undergoes dehydration at 40 degrees
      C, glass transition at 130 degrees C and decomposition at 190 degrees C by
      differential scanning calorimetry. By PXRD and moisture sorption, GW280430A is an
      amorphous material and deliquesces at about 70% RH at room temperature. Water
      acts as a potent plasticizer for GW280430A and the Tg decreases significantly as
      the water content increases. No measurable decomposition of GW280430A was
      observed after 4 weeks at 40 degrees C/75% RH.

PMID- 11839433
TI  - Evaluation of modified gum karaya as carrier for the dissolution enhancement of
      poorly water-soluble drug nimodipine.
AB  - Modified gum karaya (MGK), a recently developed excipient was evaluated as
      carrier for dissolution enhancement of poorly soluble drug, nimodipine (NM). The
      advantages of MGK over the parent gum karaya (GK) were illustrated by differences
      in the in vitro dissolution profiles of respective solid mixtures prepared by co
      grinding technique. The influence of process variable, such as polysaccharide
      concentration and method of preparation of solid mixture on dissolution rate was
      studied. Solubility studies were also performed to explain the differences in
      dissolution rate. Solid mixtures were characterized by differential scanning
      calorimetry (DSC), X-ray diffraction studies (XRD) and scanning electron
      microscopy (SEM). The dissolution rate of NM was increased as the MGK
      concentration increased and optimum ratio was found to be 1:9 w/w ratio (NM:MGK).
      It is found that method of preparation of solid mixtures was significantly
      effected the dissolution rate of NM from solid mixtures. The order of method of
      preparation in according to their Dissolution Efficiency is physical mixture < co
      grinding mixture < swollen carrier mixture < kneading mixture (water as kneading
      agent) < kneading mixture (70% v/v ethanol as kneading agent) < solid dispersion.
      Though, the solid mixtures prepared by other methods like solid dispersion,
      swollen carrier mixture and kneading technique gave faster release, co-grinding
      mixture prepared in 1:9 w/w ratio (NM:MGK) was found to exhibit a significant
      improvement in dissolution rate without requiring addition of organic solvents or
      high temperatures for its preparation and the process is less cumbersome. Hence,
      co-grinding technique appears to be more easier and the most convenient method
      from a practical point of view.

PMID- 11839435
TI  - Finite element analysis of slow drug release through deformed coating film:
      effects of morphology and average thickness of coating film.
AB  - This paper, a continuation of our previous work, is a presentation of the effect
      of the morphology and the average thickness of the deformed coating films on the
      slow diffusional release characteristics analyzed numerically under the
      constraints of the constant volume of the drug matrices and the coating films, if
      the films have the same average thickness. Increasing the average thickness of
      the coating films slows down the fractional release and the average release rate
      of the drug and smoothen the initial burst of the drug, as well as increase the
      initial lag time. The effect due to deformation of the coating films on these
      diffusional release characteristics are found to be less significant with the
      increasing average thickness of the coating films. Interestingly initial lag
      times are found to be the same for the coated particles having the same smallest
      thickness but different average thickness of coating films. The effect due to the
      change in the average thickness of the coating films on the characteristics of
      the slow controlled-release is discussed to shed light on the design of a better
      controlled-release device.

PMID- 11839436
TI  - Application of time-dependent sessile drop contact angles on compacts to
      characterise the surface energetics of sulfathiazole crystals.
AB  - The time-dependent wetting of sulfathiazole compacts with sessile water drops was
      evaluated using video microscopy. The influence of sulfathiazole crystalline
      form, particle size, pre-saturation with water, humidity and compaction pressure
      on the droplet spreading kinetics and contact angles are reported. The rate and
      extent of droplet spreading decreased for compact surfaces of high microscopic
      roughness; this was determined by atomic force microscopy (AFM). Pre-saturation
      of powder compacts with water (pre-saturated with sulfathiazole) enhanced droplet
      spreading and enabled pseudo-equilibrium contact angles to be determined for up
      to 10 min. Sessile-drop contact angles on both sulfathiazole powder compacts and
      single crystals are compared with particle contact angles determined by liquid
      penetration. This study has led to an improved understanding of the influence of
      physical heterogeneities and the face-specific surface chemistry of individual
      crystals on the wetting characteristics of pharmaceutical compacts.

PMID- 11839437
TI  - A new method to determine discoloration kinetics of uncoated white tablets
      occurring during stability testing-an application of instrumental color
      measurement in the development pharmaceutics.
AB  - The tristimulus color coordinates CIELAB and associated parameter Color Intensity
      (CI) have been shown to be a quantifiable variable for whiteness of uncoated
      tablets. Whereas any of L*, a* or b* indicates the discoloration of white tablets
      to a certain degree, it alone cannot reflect the full extent of discoloration.
      The CI has been defined which is able to describe the discoloration kinetics with
      acceptable regression coefficients. The evaluation of the CIELAB values from the
      stability data has shown that the discoloration of the white tablets means an
      intensification of yellowish or brownish color which is manifested by more or
      less constant hue angle (hab) values and increasing chroma (Cab*) values. In the
      view of these data the discoloration kinetics can physically be expressed by the
      CI. With the CI values the discoloration kinetics can be calculated by linear or
      polynomial regression with acceptable confidence intervals. The discoloration
      rates determined under several storage temperatures follow the Arrhenius equation
      and the activation energy can be estimated for the products. The CI values are
      unambiguously connected to the visual perception of the corresponding tablets. By
      means of the discoloration kinetics based on the CI values, it has become
      possible to statistically determine, the period of time uncoated tablets remain
      white.

PMID- 11839438
TI  - Enhanced bioavailability of triprolidine from the transdermal TPX matrix system
      in rabbits.
AB  - The pharmacokinetics and bioavailability of triprolidine, antihistamines, were
      studied to determine the feasibility of enhanced transdemal delivery of
      triprolidine from the poly(4-methyl-1-pentene) (TPX) matrix system containing
      polyoxyethylene-2-oleyl ether in rabbits. The triprolidine-TPX matrix (50 mg/kg)
      was applied to abdominal skin of rabbits. Blood samples were collected via
      femoral artery for 36 h and the plasma concentrations of triprolidine were
      determined by HPLC. Pharmacokinetic parameters was calculated using the LAGRAN
      computer program. The area under the curve (AUC) was significantly higher in the
      enhancer group (4058 +/- 1420 ng/ml h) than that (1902 +/- 857 ng/ml h) in
      control group (P<0.05), showing about 235% increased bioavailability. The average
      Cmax was increased significantly in the enhancer group (216 +/- 44.3 ng/ml)
      compared with control group (130 +/- 25.8 ng/ml) (P<0.05). The mean Tmax was
      increased in the enhancer group (8.0 +/- 2.55 h) compared with the control (6.0
      +/- 2.28 h) but was not significant. The relative bioavailability was 23.1% in
      the control group and 49.3% in the enhancer group compared to the oral route. As
      the triprolidine-TPX matrix containing polyoxyethylene-2-oleyl ether as an
      enhancer and tiethyl citrate as a plasticizer was administered to rabbits via the
      transdermal routes, the relative bioavailability increased by about 2.13-fold
      compared to the control group, showing a relatively constant, sustained blood
      concentration with minimal fluctuation. The results of this study shows that
      triprolidine-TPX matrix could be developed as a transdermal delivery system
      providing consistent plasma concentration.

PMID- 11839439
TI  - Tetanus toxoid microspheres consisting of biodegradable poly(lactide-co
      glycolide)- and ABA-triblock-copolymers: immune response in mice.
AB  - Tetanus toxoid (TT) was microencapsulated using poly(lactide-co-glycolide) (PLGA)
      with molar compositions of 50:50, 75:25 or an ABA-triblock-copolymer consisting
      of PLGA A-blocks attached to a central polyoxyethylene-B-block with a W/O/W
      (water/oil/water) double emulsion technique. The TT microspheres (MS) were
      evaluated with respect to protein integrity during antigen release in-vitro and
      compared with aluminum-adsorbed TT in a mouse model for in-vivo induction of
      tetanus-specific antibodies as well as protection against a subcutaneous tetanus
      toxin challenge. The more hydrophilic ABA-triblock-copolymer protected the TT
      against the deleterious microenvironmental conditions in the degrading MS and
      provided a prolonged antigen release. In spite of the distinct differences in the
      in-vitro release patterns MS from PLGA and ABA-triblock-copolymer did not show
      significant differences in the in-vivo induction of tetanus-specific antibodies.
      Both preparations elicited antibody titers nearly as high as conventional
      aluminum-adsorbed TT, which lasted for 29 weeks and were protective against a
      challenge with 100 x LD(50) tetanus toxin. TT-MS boosted mice which were
      preimmunized with aluminum-adsorbed as well as with microencapsulated TT. TT-MS
      are suitable candidates for single shot vaccine delivery systems which elicit a
      long lasting and protecting immune response.

PMID- 11839440
TI  - Polymer-cysteamine conjugates: new mucoadhesive excipients for drug delivery?
AB  - In the present study, the features of two new thiolated polymers--the so-called
      thiomers--were investigated. Mediated by a carbodiimide cysteamine was covalently
      attached to sodium carboxymethylcellulose (Na-CMC) and neutralised polycarbophil
      (Na-PCP). Depending on the weight-ratio polymer to cysteamine during the coupling
      reaction, the resulting CMC-cysteamine conjugate and PCP-cysteamine conjugate
      showed in maximum 43 +/- 15 and 138 +/- 22 micromole thiol groups per g polymer
      (mean +/- S.D.; n=3), respectively, which were used for further characterisation.
      Tensile studies carried out with the CMC-cysteamine conjugate on freshly excised
      porcine intestinal mucosa displayed no significantly (P<0.01) improved
      mucoadhesion, whereas, the mucoadhesive properties of the PCP-cysteamine
      conjugate were increased 2.5-fold compared with the unmodified polymer. The
      swelling behaviour of the CMC-cysteamine conjugate was uninfluenced by the
      covalent attachment of the sulfhydryl compound. In contrast the swelling
      behaviour of the PCP-cysteamine conjugate was improved significantly (P<0.01)
      versus unmodified PCP. Furthermore, in aqueous solutions the disintegration time
      of tablets based on the CMC- and PCP-cysteamine conjugates was prolonged 1.5 and
      3.2-fold, respectively, in comparison to tablets containing the corresponding
      unmodified polymers. According to these results, especially the PCP-cysteamine
      conjugate represents a promising new pharmaceutical excipient for various drug
      delivery systems.

PMID- 11839441
TI  - Intestinal transport of cefuroxime axetil in rats: absorption and hydrolysis
      processes.
AB  - Studies were performed using three cefuroxime axetil solutions (11.8, 118 and 200
      microM) in three selected intestinal segments and one cefuroxime axetil solution
      (118 microM) in colon of anaesthetized rats. First-order absorption rate
      pseudoconstants, k(ap) and effective permeability coefficients, P(eff), were
      calculated in each set. Absorption of cefuroxime axetil can apparently be
      described as a carrier-mediated transport, which obeys Michaelis-Menten and first
      order kinetics in the proximal segment of the small intestine and a passive
      diffusion mechanism in the mean and distal segments. The absorption kinetic
      parameters for cefuroxime axetil were obtained: Vm=0.613 (0.440) microM min-1;
      Km=31.49(28.31) microM and ka=0.011(0.003) min-1. Parameters characterizing
      degradation of the prodrug were obtained in each intestinal segment: proximal
      segment k(dp)=0.0049(0.0003) min-1, mean segment, k(dm)=0.0131(0.0007) min-1 and
      distal segment k(dd)=0.019(0.0009) min-1. Therefore, in situ intestinal
      absorption of cefuroxime axetil in the proximal segment of the rat in the
      presence of variable concentrations of cefadroxil has been investigated in order
      to examine the inhibitory effect of cefadroxil on cefuroxime axetil transport.
      The data suggest that cefadroxil and cefuroxime axetil share the same intestinal
      carrier.

PMID- 11839442
TI  - Intestinal absorption characteristics of the low solubility thiocarboxanilide UC
      781.
AB  - The aim of this study was to determine the intestinal absorption characteristics
      of the antiviral agent UC-781 and to optimize the experimental conditions of the
      in vitro system for low solubility compounds. The absorption potential of UC-781
      was studied with the Caco-2 system and with the rat intestinal perfusion
      technique. The low solubility of UC-781 required the use of
      solubility/dissolution rate enhancing agents (e.g. VitE-TPGS, Gelucire 44/14).
      The creation of sink conditions in the receiver compartment of the Caco-2 system
      was a prerequisite to reliably study the transport of this poorly soluble
      compound. After inclusion of VitE-TPGS in the acceptor solution, UC-781 could be
      characterized as a class II drug of the Biopharmaceutical Classification System
      (low solubility, high permeation across membranes). A significant concentration
      dependent decrease in transport of UC-781 was observed upon increasing the
      concentration of VitE-TPGS in the apical compartment. This observation contrasts
      to the absorption enhancing properties of VitE-TPGS, and can probably be
      attributed to a decrease in the concentration of free UC-781 when using higher
      concentrations of the solubility/dissolution rate enhancing agents. The use of
      Gelucire 44/14 as a solubilizing agent resulted in a batch-dependent degradation
      of UC-781. The inclusion of the solubility/dissolution rate-enhancing agent VitE
      TPGS did not result in absorption enhancement in the intestinal perfusion
      technique.

PMID- 11839443
TI  - Enhancement of skin permeation of miconazole by phospholipid and dodecyl 2-(N,N
      dimethyl amino)propionate (DDAIP).
AB  - Miconazole (MCZ) has very low solubility in both water and oil. Permeation rates
      through shed snakeskin from an aqueous suspension and a mineral oil suspension
      were 0.5 microg/cm(2)/h and almost none, respectively. When hydrogenated
      phosphatidylcholine (HPC) was added to mineral oil and heated to 95 degrees C,
      the solubility of MCZ increased in proportion to the HPC concentration. DSC
      measurements also indicated an interaction between them. Thus, a gel formed by
      hydrogenated phospholipid and mineral oil, as vehicle was prepared. The
      solubility of MCZ in the gel was around 1% and the permeation rate was 1.3
      microg/cm(2)/h, which was about 2.5 times that from an aqueous suspension. As an
      alternative approach, a skin permeation enhancer, dodecyl 2-(N,N-dimethyl
      amino)propionate (DDAIP) was applied 2 h before a skin permeation study. The
      permeation from an aqueous suspension became 11 times that of the suspension
      without DDAIP pretreatment. The concentration of MCZ in the skin increased 8
      fold, indicating that the enhancement effect involved high partition of MCZ into
      the skin. On the other hand, when a gel formulation was used, pretreatment with
      DDAIP was not as effective as incorporation of DDAIP in the gel formulation.
      Following pretreatment, permeation was only two times that of the gel without
      DDAIP pretreatment, and half that of the water suspension with DDAIP
      pretreatment. This suggested that release from the gel was the rate-limiting step
      with the gel formulation. When DDAIP was added to the gel, the permeation rate of
      MCZ was 3.3 microg/cm(2)/h. It was also a release limited type permeation. The
      gel with DDAIP is potentially a useful formulation, because of relatively high
      permeation while possibly avoiding overdosing.

PMID- 11839445
TI  - Application of a factorial design to the study of specific parameters of a
      Carbopol ETD 2020 gel. Part I. Viscoelastic parameters.
AB  - This work studies the application of a 2(3) factorial design to a cosmetic gel
      with the aim of simplifying the analysis of the influence of the concentration of
      Carbopol ETD 2020 (cb), of ethanol (et) and of glycerin (gl) on the viscoelastic
      parameters: equilibrium modulus (Gn), critical molecular weight (Mc), degree of
      structuring (logG'/lognu) and viscous modulus (G"). We have obtained high linear
      polynomial correlations among the components and the response factors determined.
      The results obtained evidence the usefulness of this type of technique in
      detecting interactions among the components that would be difficult to foresee
      otherwise. Mc, logG'/lognu and G" depend on the interaction cb-et. Gn depends on
      the interaction of cb-et-gl. That is, an increase in gl can increase or decrease
      the elasticity (Gn) of the gels, depending on the concentrations of cb and et.

PMID- 11839444
TI  - Co-delivery of an antisense oligonucleotide and 5-fluorouracil using sustained
      release poly (lactide-co-glycolide) microsphere formulations for potential
      combination therapy in cancer.
AB  - Antisense oligonucleotides (AODNs) can selectively inhibit oncogene expression by
      Watson-Crick hybridisation to target mRNA and are being increasingly considered
      for use in combination with conventional drugs for potential anticancer therapy.
      Combination therapy of AODNs and cytotoxic agents using biodegradable polymeric
      delivery systems potentially offers several advantages including site-specific or
      organ-directed targeting, protection from digesting enzymes, and improved
      pharmacokinetics/pharmacodynamics resulting from sustained delivery of the
      entrapped drugs. Using a model AODN targeting the epidermal growth factor
      receptor (that is over-expressed in several cancers including breast and brain
      cancer) and the commonly used cytotoxic agent, 5-fluorouracil (5-FU), we have
      examined the use of poly (lactide-co-glycolide) (P(LA-GA)) microsphere
      formulations for co-delivery of these agents. Both agents were either co
      entrapped in a single microsphere formulation or individually entrapped in two
      separate microsphere formulations and release profiles determined in vitro. Using
      a double emulsion method for preparing the P(LA-GA) microspheres suitable
      entrapment and sustained release over 35 days was observed in both types of
      formulation. Release of AODN and 5-FU from all formulations appeared to be
      biphasic. However, the release rates of the two agents were significantly slower
      when co-entrapped as a single microsphere formulation compared to those obtained
      with the separate formulations. Electrophoretic mobility shift assays suggested
      that this might be, in part, due to an interaction of 5-FU with the
      oligodeoxynucleotide (ODN). Further, our data suggest that by mixing individual
      formulations of 5-FU and ODNs at different mass ratios allowed greater
      flexibility in achieving the desired release profile as well as avoiding
      potential drug-drug interactions. Thus, co-administration of individual P(LA-GA)
      microsphere formulations of AODNs and 5-FU, at appropriate mass ratios, appears
      worthy of further investigation for the potential co-delivery of these anti
      cancer agents in vivo.

PMID- 11839446
TI  - Application of a factorial design to the study of the flow behavior,
      spreadability and transparency of a Carbopol ETD 2020 gel. Part II.
AB  - A factorial design (2(3)) is applied to study the influence of three of the
      components of a cosmetic gel (the concentrations of Carbopol ETD 2020, ethanol
      and glycerine) on flow parameters (Casson's yield value (tau(c)), Casson's
      viscosity (eta(c)) and apparent viscosity at 125 s-1 (eta(ap.) 125 s-1),
      spreadability, and transparency. The first-order polynomial equation allowed by
      the model suitably accounts for the tau(c) and spreadability. Both depend on the
      concentrations of Carbopol and ethanol, and tau(c) also depends on the ethanol
      glycerine interaction. The model explains to a certain extent the complex
      relationships that are established between the components and that influence
      eta(c) y eta(ap.) 125 s-1. Transparency is independent of the Carbopol
      concentration and it is also thought to be independent of the ethanol
      concentration. In addition, a high linear correlation has been found between the
      tau(c) and spreadability and other viscoelastic parameters of the gels that were
      previously determined (Int. J. Pharm. (2001)). The application of the technique
      of experimental design has been shown to be a very useful tool for formulating
      gels.

PMID- 11839447
TI  - The rate of absorption and relative bioavailability of caffeine administered in
      chewing gum versus capsules to normal healthy volunteers.
AB  - OBJECTIVE: The purpose of this study was to evaluate the rate of absorption and
      relative bioavailability of caffeine from a Stay Alert chewing gum and capsule
      formulation. METHODS: This was a double blind, parallel, randomized, seven
      treatment study. The treatment groups were: 50, 100, and 200 mg gum, 50, 100, and
      200 mg capsule, and a placebo. Subjects consisted of 84 (n=12 per group);
      healthy, non-smoking, males who had abstained from caffeine ingestion for at
      least 20 h prior to dosing and were randomly assigned to the treatment groups.
      Blood samples were collected pre-dose and at 5, 15, 25, 35, 45, 55, 65, 90 min
      and 2, 3, 4, 6, 8, 12, 16 and 29 h post administration. Plasma caffeine levels
      were analyzed by a validated UV-HPLC method. RESULTS: Mean Tmax for the gum
      groups ranged from 44.2 to 80.4 min as compared with 84.0-120.0 min for the
      capsule groups. The Tmax, for the pooled data was significantly lower (P<0.05)
      for the gum groups as compared with the capsule groups. Differences in Tmax were
      significant for the 200 mg capsule versus 200 mg gum (P<0.05). The mean ka values
      for the gum group ranged from 3.21 to 3.96 h-1 and for the capsule groups ranged
      from 1.29 to 2.36 h-1. Relative bioavailability of the gum formulation after the
      50, 100 and 200 mg dose was 64, 74 and 77%, respectively. When normalized to the
      total drug released from the gum (85%), the relative bioavailability of the 50,
      100 and 200 mg dose were 75, 87, and 90%, respectively. No statistical
      differences were found for Cmax and AUCinf for comparisons of the gum and capsule
      formulations at each dose. Within each dose level, there were no significant
      formulation related differences in Cmax. No significant differences were observed
      in the elimination of caffeine after the gum or capsule. CONCLUSIONS: The results
      suggest that the rate of drug absorption from the gum formulation was
      significantly faster and may indicate absorption via the buccal mucosa. In
      addition, for the 100 and 200 mg groups, the gum and capsule formulations provide
      near comparable amounts of caffeine to the systemic circulation. These findings
      suggest that there may be an earlier onset of pharmacological effects of caffeine
      delivered as the gum formulation, which is advantageous in situations where the
      rapid reversal of alertness and performance deficits resulting from sleep loss is
      desirable.

PMID- 11839448
TI  - Principal component analysis of dissolution data with missing elements.
AB  - The use of principal component analysis (PCA) for incomplete dissolution data
      sets is examined. The PC space is constructed using a reference set and the test
      set is projected in that space. Several cases such as a reference set with
      missing data, an incomplete test set and both sets measured at different time
      points, are discussed using two examples: one simulation and one obtained from
      the pharmaceutical practice. From the many possibilities to deal with missing
      data, the expectation-maximization algorithm in combination with PCA was chosen.
      The influence on the similarity or f2 factor is examined too. The sampling with
      replacement or bootstrap technique, which can be used to obtain confidence
      limits, can also be used when missing data are present in one of the data sets.

PMID- 11839449
TI  - Optimization and characterization of controlled release multi-particulate beads
      formulated with a customized cellulose acetate butyrate dispersion.
AB  - The objectives of the present investigation were: (1) to model the effect of
      process and formulation variables viz., coating weight gain, duration of curing,
      and plasticizer concentration on in-vitro release profile of verapamil HCl from
      multi-particulate beads formulated with a novel aqueous-based pseudolatex
      dispersion; (2) to optimize the formulation by response surface methodology (RSM)
      and artificial neural network (ANN); and (3) to characterize the optimized
      product by thermal and X-ray analyses. Inert beads (Nupareil) were loaded with
      verapamil HCl and subsequently coated with a custom designed aqueous-based
      pseudolatex dispersion of cellulose acetate butyrate (CAB). Experiments were
      designed and data was collected according to a three factor, three level face
      centered central composite design. Data was analyzed for modeling and optimizing
      the release profile using both RSM and ANN. Model fitted the data and explained
      90% of variability in response in the case of RSM and at least 70% in the case of
      ANN. Release profile was optimized for a zero-order model. Optimized formulations
      were prepared according to the factor combinations dictated by RSM and ANN. In
      each case, the observed drug release data of the optimized formulations was close
      to the predicted release pattern. However, the modeling and optimization
      abilities of RSM as evaluated by the R-squared values, were found to be higher
      than that of ANN. X-ray and drug content analysis suggested the absence of any
      degradation of verapamil HCl and excipients incorporated in the formulation.

PMID- 11839450
TI  - Preparation and characterization of fentanyl-loaded PLGA microspheres: in vitro
      release profiles.
AB  - We developed several kinds of fentanyl-loaded poly(L-lactide-co-glycolide) (PLGA)
      microspheres (FMS) for sustained release of fentanyl. FMS were prepared by an
      emulsion solvent-evaporation method. In this study, the influences of several
      preparation parameters, such as initial drug loading, polymer concentration, and
      solvent volume on the release patterns of fentanyl were investigated.
      Furthermore, it has been well noted that the detection of fentanyl is extremely
      difficult because its clinical dose level is very low, about 1-3 ng/ml, in cancer
      patient treatment. Therefore, we also developed a rapid and sensitive
      determination method for fentanyl in systemic circulation by employing gas
      chromatography (GC) system. Fentanyl was slowly released from FMS over 15 days
      with a quasi-zero order property. From the results, our FMS may be good
      formulations to deliver the analgesics and suitable for the treatment of severe
      pain over long periods.

PMID- 11839451
TI  - Impact of deep freezing on the stability of 25 mg/ml vancomycin ophthalmic
      solutions.
AB  - For the treatment of certain eye infections, ophthalmic solutions 'laced' with 25
      mg/ml vancomycin are sometimes prepared. Their physical and chemical stability
      and the maintenance of their sterility were studied after deep freezing at -20 +/
      2 degrees C and thawing, followed or not by refrigeration for 48 h at 4 +/- 2
      degrees C. Physical and chemical analysis comprised visual inspection turbidity,
      determination of pH and osmolality, and assay of vancomycin by high performance
      liquid chromatography with ultraviolet detection. For microbiological analysis a
      25 mg/ml vancomycin ophthalmic solution was filtered through two membranes and
      cultured on trypticase-soy and Sabouraud-glucose solid media. Any colonies were
      then counted. These physical, chemical and microbiological analyses demonstrated
      the stability of 25 mg/ml vancomycin ophthalmic solutions in 5% glucose deep
      frozen at -20 +/- 2 degrees C for 3 months. The vancomycin concentration varied
      by no more than 5% of the initial concentration, and no breakdown product was
      evidenced. Neither pH (mean=3.8 +/- 0.1) nor osmolality (mean=318.3 +/- 5.6
      mOsm/kg) varied significantly, and remained compatible with intraocular
      administration. No particle or bacterial combination was found in the course of
      the study. The thawing procedure (at ambient temperature or under warm running
      water from a tap) did not modify the stability of the eye drops. Likewise,
      storage in a refrigerator for 48 h after thawing did not modify stability. The
      advantage of storing vancomycin 25 mg/ml ophthalmic solutions for 3 months in
      deep freeze is that a stock of chemically and microbiologically controlled
      preparations can be held ready for administration to patients, thereby allowing
      prompter dispensing, as the eye drops are not made up extemporaneously, while the
      improved control over production ensures that patients receive solutions of
      constant quality, as every batch prepared is systematically inspected.

PMID- 11839452
TI  - Development of sustained release matrix tablets of didanosine containing
      methacrylic and ethylcellulose polymers.
AB  - Didanosine, a nucleoside analog used in the treatment of acquired immuno
      deficiency syndrome (AIDS), has been incorporated into directly compressed
      monolythic matrices whose excipients were mixtures at different ratios of a
      methacrylic resin (Eudragit RSPM) and an ethylcellulose (Ethocel 100), both water
      insoluble and pH-independent polymers. Technological characterization (drug
      particle morphology, mean weight, diameter, thickness and hardness of tablets)
      was carried out and in vitro drug release behaviour was measured using the USP
      basket apparatus. The effect of varying the Eudragit-Ethocel ratio, as well as
      the drug-polymeric matrix ratio, was evaluated. The results showed the
      suitability of Eudragit-Ethocel mixtures as matrix-forming material for
      didanosine sustained release formulations. Combination of the moderate swelling
      properties of Eudragit RSPM with the plastic properties of the more hydrophobic
      Ethocel 100 allowed suitable modulation of didanosine release.

PMID- 11839453
TI  - Diethyl ether fraction of Labrasol having a stronger absorption enhancing effect
      on gentamicin than Labrasol itself.
AB  - In our previous study, we had reported that Labrasol has a good gastrointestinal
      (GI) absorption enhancing effect on poorly absorbable drugs. In order to improve
      further absorption enhancing effect of Labrasol on gentamicin (GM), which is a
      representative water-soluble, poorly absorbable drug, Labrasol was fractionated
      with hexane, diethyl ether, ethyl acetate and water. The absorption enhancing
      effect of each fraction of Labrasol and Labrasol alone were evaluated in vivo
      using rats. Each test formulation of GM was administered into the rat colon at a
      dose of 5.0 mg/kg and plasma GM concentrations were measured by a HPLC method.
      Among the four fractions of Labrasol and Labrasol, diethyl ether fraction showed
      the strongest absorption enhancing effect on GM. When the doses of diethyl ether
      fraction were 1.0, 0.5 and 0.1 ml/kg, the Cmax values were 8.95 +/- 1.46, 8.02 +/
      2.14 and 7.41 +/- 1.25 microg/ml, respectively. Moreover, AUC(0-6) values were
      also maintained at high level, i.e. 27.28 +/- 5.90, 20.32 +/- 3.79 and 19.61 +/-
      2.09 microg h/ml. Based on the AUC(0-6) values obtained with each fraction, the
      rank order of absorption enhancing effect on GM was diethyl ether > ethyl
      acetate=hexane > aqueous fraction.

PMID- 11839454
TI  - Niosomes as carriers for tretinoin. I. Preparation and properties.
AB  - Tretinoin-loaded niosomes were prepared from polyoxyethylene (4) lauryl ether,
      sorbitan esters and a commercial mixture of octyl/decyl polyglucosides, in the
      presence of cholesterol and dicetyl phosphate. Liposomes made of hydrogenated and
      non-hydrogenated phosphatidylcholine were also prepared as a comparison
      reference. A study was made of the influence of vesicle composition and
      preparation method on the vesicle structure (MLV, LUV, SUV), size distribution,
      entrapment efficiency and in vitro release of incorporated tretinoin. Results
      showed that in the presence of cholesterol all the amphiphiles used were able to
      form stable vesicle dispersions with or without tretinoin. Vesicle sizes were
      dependent on the preparation method, bilayer composition and drug load.
      Multilamellar (MLV) vesicles were larger than extruded (LUV) and sonicated (SUV)
      vesicles while drug-loaded vesicles were generally smaller than empty ones.
      Entrapment efficiencies of tretinoin were always very high especially for
      multilamellar (91-99%) and extruded (88-98%) vesicles. The in vitro release of
      tretinoin from the prepared vesicular formulations was studied using the vertical
      Franz diffusion cells. The rate of drug release through a Silastic membrane from
      a liposomal and niosomal tretinoin dispersion was generally faster than from a
      tretinoin solution. Release data showed that tretinoin delivery is mainly
      affected by the vesicular structure and that tretinoin delivery increased from
      MLVs to LUVs to SUVs.

PMID- 11839456
TI  - Effect of an external resistance to airflow on the inspiratory flow curve.
AB  - Inhalation is a convenient way to deliver drugs to the respiratory tract in the
      treatment of respiratory diseases. For dry powder inhalers (DPI's), the principle
      of operation is to use the patient-generated inspiratory flow as energy source
      for emptying of the dose system and the delivery of fine drug particles into the
      respiratory tract. Resistance to airflow of the inhaler device is a major
      determinant for the inspiratory flow profile through the dry powder inhaler that
      can be generated by the patient. Therefore, resistance to airflow is one of the
      design parameters for DPI's, that could be used to control the inspiratory flow
      profile, and is one of the parameters to optimise particle deposition in the
      airways. In this study the effect of resistance to airflow on different
      parameters of the inspiratory flow curves as generated by healthy subjects,
      asthmatics and COPD patients was determined. As a result of increased resistance
      to airflow, the peak inspiratory flow (PIF), the flow increase rate (FIR) and the
      inhaled volume to reach PIF is decreased. On the other hand, the total inhalation
      time as well as the 80% dwell time is increased. In general, tuning of the
      resistance to airflow in the design of a dry powder inhaler may improve the drug
      deposition in the respiratory tract.

PMID- 11839455
TI  - Spectrophotometric investigation of the binding of vitamin E to water-containing
      reversed micelles.
AB  - The distribution constants of vitamin E partitioned between apolar organic phase
      and water-containing reversed micelles of sodium bis (2-ethylhexyl)
      sulfosuccinate (AOT), didodecyldimethylammonium bromide (DDAB), soybean
      phosphatidylcholine (lecithin) and tetraethylene glycol monododecyl ether (C12E4)
      have been evaluated by a spectrophotometric method. The results suggest that in
      the presence of domains from apolar organic solvent to surfactant and to water,
      vitamin E is partitioned between the micellar palisade layer and the organic
      solvent and also that its binding strength to reversed micelles depends mainly by
      specific interactions between the head group of vitamin E and that of the
      surfactant. Moreover, in addition to the advantageous interactions between
      vitamin E and water, the dependence of the distribution constants upon the molar
      ratio R (R=[water]/[surfactant]) indicates a competition between water and
      vitamin E for the binding sites at the water/surfactant interface. The biological
      implications of the preferential location and confinement of vitamin E in water
      containing reversed micelles are discussed.

PMID- 11839457
TI  - Prolonged neurophysiological effects of cumulative wine drinking.
AB  - The effects of a single, large dose of alcohol have been studied extensively, but
      how alcohol affects the brain under more realistic social drinking situations has
      received scant attention. The neurophysiological effects of a cumulative dose of
      alcohol were investigated as subjects drank three glasses of alcoholic or placebo
      red wine, 1 h apart. In a double-blind procedure, electroencephalographic (EEG)
      activity was recorded for social drinkers during rest and performance of a
      working memory task at two levels of difficulty. Background EEG power in the
      theta, slow alpha, and beta bands increased with alcohol consumption. Along with
      this systemic increase in background cortical resonant activity, event-related
      potential (ERP) amplitudes decreased between 200 and 350 ms poststimulus and P300
      latency increased, effects that occurred while relevant stimulus factors were
      being evaluated. These neurophysiological effects endured 3 h after drinking,
      whereas blood/breath alcohol concentration had decreased considerably and
      cognitive performance returned to normal. These findings seem to indicate that
      moderate social alcohol consumption has cumulative effects on brain function that
      persist for hours after chemical and behavioral indicators of intoxication have
      diminished. The results seem to indicate that neuronal populations needed for
      stimulus processing were less available after wine consumption (as evidenced by
      reduced ERP amplitudes) because of increased background oscillatory activity (as
      evidenced by increased background EEG power).

PMID- 11839458
TI  - Sleep disturbances after acute exposure to alcohol in mothers' milk.
AB  - The results of previous research in our laboratory revealed that breast-fed
      infants experience significantly less active sleep after exposure to alcohol in
      their mothers' milk than do breast-fed infants not exposed to alcohol. The
      present study tested the hypothesis that infants would compensate for such
      reductions if their mothers then refrained from drinking alcohol. To this end, 23
      breast-fed infants from 3 to 5 months of age and their mothers were tested on 2
      days separated by 1 week. A small, computerized movement detector, an actigraph,
      was placed on the infants' left ankles to monitor sleep and activity patterning
      after which they were bottle fed mother's milk alone (control condition) on 1
      test day and mother's milk containing 32 mg of ethanol per 100 ml--the average
      concentration detected in human milk after lactating women drank an acute dose
      (0.3 g/kg) of alcohol--on the other. The infants' behaviors were monitored for
      the next 24 h; the first 3.5 h of monitoring on each test day took place at the
      Monell Center. Consistent with previous findings, infants exhibited significantly
      less active sleep during the 3.5 h immediately after exposure to alcohol in
      mothers' milk compared with the control condition; the decrease in active sleep
      was observed in all but 4 of the infants tested. Compensatory increases in active
      sleep were then observed in the next 20.5 h, when mothers refrained from drinking
      alcohol. Although the mechanisms underlying the reduction in sleep remain to be
      elucidated, these findings demonstrate that short-term exposure to small amounts
      of alcohol in mothers' milk produces distinctive changes in the infants' sleep
      wake patterning.

PMID- 11839459
TI  - Malondialdehyde-acetaldehyde-adducted bovine serum albumin activates protein
      kinase C and stimulates interleukin-8 release in bovine bronchial epithelial
      cells.
AB  - Previous study results have demonstrated that cigarette smoke or acetaldehyde
      rapidly stimulates protein kinase C (PKC)-mediated release of interleukin-8 (IL
      8) in bovine bronchial epithelial cells (BECs). Low concentrations of
      acetaldehyde combine synergistically with malondialdehyde to increase
      significantly maximal BEC PKC activity at 48 to 96 h stimulation. Because more
      than 95% of alcoholics are cigarette smokers, we hypothesized that
      malondialdehyde, an inflammation product of lipid peroxidation, and acetaldehyde,
      both a product of ethanol metabolism and a component of cigarette smoke, might
      stimulate PKC-mediated IL-8 release in BECs by malondialdehyde-acetaldehyde (MAA)
      adduct formation, rather than as free aldehydes. Protein kinase C activity is
      maximally elevated in BECs treated with 50 microg/ml of BSA-MAA from
      approximately 1 to 3 h. This activity subsequently begins to decrease by 4 to 6
      h, with a return to baseline unstimulated kinase activity levels by 24 h. No
      activation of cyclic AMP-dependent protein kinase (PKA) or cyclic GMP-dependent
      protein kinase (PKG) was observed in BSA-MAA-treated BECs. The MAA adduct
      activation of PKC was followed by a fourfold to tenfold greater release of IL-8
      over that observed for both BECs exposed to media only and BSA control-treated
      BECs. Protein kinase C activation and IL-8 release were blocked by pretreating
      BECs with 1 microM calphostin C or 100 nM of the PKC alpha-specific inhibitor, Go
      6976. Isoform-specific inhibitors to PKC beta, PKC delta, and PKC zeta failed to
      inhibit completely MAA adduct-stimulated PKC or IL-8 release. Results of these
      studies indicate that metabolites derived from ethanol and cigarette smoke, such
      as acetaldehyde and malondialdehyde, form adducts that stimulate airway
      epithelial cell PKC alpha-mediated release of promigratory cytokines.

PMID- 11839461
TI  - Alcohol biomarkers: clinical significance and biochemical basis.

PMID- 11839462
TI  - Plasma sialic-acid index of apolipoprotein J (SIJ): a new alcohol intake marker.
AB  - Although plasma carbohydrate-deficient transferrin (CDT) is considered a viable
      biochemical marker for chronic alcohol consumption, it is valid only when an
      individual's daily alcohol consumption exceeds 60 g. In addition, it is less
      sensitive in women drinkers than in men drinkers. We have established that
      chronic alcohol consumption impairs the hepatic sialylation of a number of
      glycoproteins by specifically down-regulating Gal-beta-1,4GlcNAc alpha2,6
      sialyltransferase mRNA. Significantly, we found that chronic ethanol consumption
      markedly inhibits hepatic sialylation of apolipoprotein J (Apo J), a 70-kDa N
      glycosylated protein of plasma HDL. Because the sialic-acid index of Apo J (SIJ;
      moles of sialic acid per mole of Apo J protein) is approximately seven times more
      than that for transferrin (28 vs. 4), we have evaluated whether plasma SIJ would
      be an even more sensitive marker for chronic ethanol consumption than CDT in both
      rats and human subjects. The method involves immunoaffinity purification of
      plasma HDL-Apo J, followed by its sialic acid determination. We have found that
      chronic ethanol feeding resulted in loss of sialic acid residues of plasma HDL
      Apo J in rats. This loss of sialic acid was positively correlated with both
      amount and duration of ethanol treatment. In human subjects, an intake of about
      60 g of alcohol for 30 days led to almost 50% (P <.01) depletion of sialic acid
      from plasma HDL-Apo J. Further, we established that there was a positive
      correlation of alteration in SIJ with alcohol consumption, detoxification,
      abstinence, and relapse in human alcohol-dependent patients (sensitivity, 90%
      92%). In addition, plasma SIJ was decreased by 50%-57% (P <.01) in both male and
      female alcohol-dependent subjects. We suggest that plasma SIJ can be used as a
      viable marker for early detection of chronic alcohol consumption in human beings.

PMID- 11839463
TI  - Usefulness of microheterogeneity of serum alpha 1-acidglycoprotein as a marker
      for alcohol abuse.
AB  - Carbohydrate-deficient transferrin is considered to be the most sensitive and
      specific biological marker of alcohol abuse. However, in alcohol-dependent
      individuals, microheterogeneity is also found in other glycoproteins besides
      transferrin. In this study, we compared the appearance of microheterogeneity in
      serum transferrin and alpha(1)-acidglycoprotein to clarify whether
      microheterogeneity of alpha(1)-acidglycoprotein is a marker for alcohol abuse.
      Serum samples were obtained from alcohol-dependent individuals with and without
      liver disease (LD) and non-alcohol-dependent patients with LD. Microheterogeneity
      of serum transferrin and alpha(1)-acidglycoprotein was determined by Western
      blotting. Microheterogeneity of transferrin and alpha(1)-acidglycoprotein was
      detected, respectively, in 63.2% and 58.5% of patients with alcoholic LD.
      Microheterogeneity of transferrin was not detected in alcohol-dependent
      individuals without LD, whereas microheterogeneity of alpha(1)-acidglycoprotein
      was detected in 42.9%. In non-alcohol-dependent patients with decompensated
      cirrhosis, microheterogeneity of transferrin and alpha(1)-acidglycoprotein was
      detected, respectively, in 68.4% and 15.8%. In conclusion, microheterogeneity of
      serum alpha(1)-acidglycoprotein may be a useful marker for chronic alcohol
      drinking.

PMID- 11839464
TI  - Carbohydrate-deficient transferrin for detection and monitoring of sustained
      heavy drinking. What have we learned? Where do we go from here?
AB  - Carbohydrate-deficient transferrin (CDT) has been widely investigated as a
      biological marker of heavy alcohol consumption. In general, it has been found to
      be at least as sensitive and probably more specific than gamma
      glutamyltransferase (GGT). Because the two analytes are not highly correlated,
      their use in parallel enhances the sensitivity of detection of heavy alcohol
      consumption, especially in clinical populations. Women as a group produce more
      CDT under natural conditions and may produce less CDT in response to heavy
      drinking. Carbohydrate-deficient transferrin has found a place in the monitoring
      of alcoholics during treatment. Changes in CDT levels from individualized
      baseline values seem to be more sensitive to lower level relapse drinking than is
      the use of raw cut-off values. There are some conditions such as severe liver
      disease in which higher than normal levels of CDT are produced, thereby reducing
      the specificity of this marker for detecting heavy drinking under certain
      conditions. Future directions for the use of CDT include standardization and
      automation of measurement technology, evaluation of how to use it wisely in
      myriad medical and institutional settings, understanding more thoroughly the
      gender issues in its production, and greater evaluation of its performance as a
      monitoring tool during treatment and follow-up situations. How to combine CDT
      with both verbal tools of alcohol assessment and newer biological markers will
      also need more extensive evaluation.

PMID- 11839465
TI  - Sensitivity and specificity of carbohydrate-deficient transferrin in drinking
      experiments and different patients.
AB  - Information provided by patients about the amounts of alcohol they drink may
      often be too subjective and therefore unreliable. Because of the possible serious
      consequences of interactions between alcohol and medication, reliable laboratory
      test markers for alcohol consumption are needed. Carbohydrate-deficient
      transferrin (CDT) is at present the best available objective measure of drinking
      behavior. During a withdrawal trial, 92 alcohol-dependent patients who had been
      admitted to a hospital in an ethanol-intoxicated state were monitored over the
      following 28 days by using the percent carbohydrate-deficient transferrin (%CDT
      of total transferrin) (%CDT) method. At the time of admission, 63% showed
      elevated %CDT levels. After a subsequent period of abstinence, a decrease in %CDT
      levels was apparent in four different groups of patients, whereas in two groups,
      comprising the greatest number of patients, normal %CDT levels were evident after
      14 days of abstinence. In patients whose CDT levels were very high at study
      initiation, it took at least 21 to 28 days--and sometimes longer--for CDT to
      decrease to the radioimmunoassay (RIA) %CDT test cutoff point of 2.5. In a
      further study of 56 male alcohol-dependent patients, we measured liver enzyme
      concentrations, mean corpuscular volume (MCV), and four CDT variants on the first
      day of evidence of withdrawal syndrome. We found a significant correlation
      between results on the Munich Alcoholism Test (MALT) and MCV levels; among gamma
      glutamyltransferase (GGT), aspartate aminotransferase (AST), and alanine
      aminotransferase (ALT) levels; and among all four CDT variants. A cluster
      analysis yielded three clusters: (1) GGT, AST, and ALT levels; (2) MCV levels and
      MALT results; and (3) all CDT measurement variants. We conclude that these three
      clusters measure different detriments to the patient and that all available CDT
      variants are commensurate.

PMID- 11839466
TI  - Chronic ethanol exposure in rats affects rabs-dependent hepatic trafficking of
      apolipoprotein E and transferrin.
AB  - Because of the important roles of rabs in protein trafficking, we tested whether
      chronic ethanol exposure affected the trafficking of newly synthesized
      apolipoprotein E (apoE) or transferrin (O-glycosylated and N-glycosylated
      proteins, respectively) attached to acylated or prenylated rabs. The in vivo 30
      min incorporation ratios of [3H]palmitate:[35S]methionine or
      [3H]mevalonate:[35S]methionine (relative ratios of rabs acylation or prenylation
      to total protein or to immunoisolated apoE or transferrin) were measured in
      various hepatic subcellular organelles of 8 week-ethanol-fed (E) and pair-fed
      control (C) Wistar-Furth rats. With respect to total protein trafficking, ethanol
      increased rabs acylation ratio by 136% (P <.01), 69% (P <.05), and 64% (P <.01)
      in the endoplasmic reticulum (ER), Golgi light fraction (GLF), and Golgi heavy
      fraction (GHF), respectively, and decreased this ratio by 76% (P <.01) in carrier
      vesicle fraction 2 (CV2). With respect to apoE trafficking, ethanol increased
      rabs acylation ratio by 121% in GHF and decreased this ratio by 27% in CV2. Rabs
      prenylation ratio increased by 21% and 53% in GHF and CV2, respectively, and
      decreased by 42% in GLF. With respect to transferrin trafficking, ethanol
      increased rabs acylation ratio by 53% (P <.01) in GHF, with no significant effect
      in ER, whereas rabs prenylation ratio increased by 26% (P <.05) in ER, with no
      significant effect in GHF. Therefore, we conclude that ethanol-induced impaired
      trafficking of newly synthesized O- and N-glycosylated proteins occurs primarily
      in ER and Golgi and is due to altered lipidation of rabs, possibly rabs 1, 2, or
      6 or combinations of these three rabs.

PMID- 11839467
TI  - Selection of phage-display library peptides recognizing ethanol targets on
      proteins.
AB  - There is a forthcoming link between chronic alcohol consumption and proteins
      covalently modified by ethanol metabolites and their antibodies. To identify
      sensitive probes of protein-ethanol conjugates, we screened for the ethanol
      altered protein domains with a phage-display combinatorial peptide library. In
      principle, recognition of the epitopes by the library peptides occurs through
      protein-protein interactions. A general screening, M13-based library with 10(9)
      random sequences of linear heptameric peptides was used. The peptides were
      displayed in five copies each, as fusion proteins with phage's minor coat protein
      III. They were located on one end of the surface of the phage particles. The
      targets were a model protein, streptavidin, and protein-ethanol conjugates
      (hydroxyethyl radical- or acetaldehyde-modified bovine serum albumin). They were
      either immobilized on a surface by direct coating or affinity captured on
      floating beads. An enriched library of phages with the tightest peptide binders
      for each target was selected and amplified in a multiple-cycle biopanning in
      vitro procedure. Binders were characterized by DNA sequencing of the
      corresponding phages and by counter-screening with positive and negative targets
      in either an enzyme-linked immunosorbent assay or plaque assay. We obtained the
      HPQ motif for streptavidin and two unique subsets of peptides that recognized
      each ethanol target with a selectivity of two orders of magnitude above the
      carrier protein and controls. The application of biopanning processes, coupled
      with phage-display peptide libraries on biological fluids and tissues, could
      provide a systematic mapping of protein--ethanol conjugates and supply a means
      for early diagnosis and prognosis of chronic alcohol consumption in human beings.

PMID- 11839468
TI  - Biosensors in fish production and quality control.
AB  - Fishery products are important not only from a nutritional point of view, but
      also as an item of international trade and foreign exchange earner for a number
      of countries in the world. Fish and shellfish are highly perishable, and prone to
      vast variations in quality due to differences in species, environmental habitats,
      feeding habits, etc. In addition, they can also function as carriers of several
      microbial and other health hazards. Therefore, maintenance of quality is of
      utmost importance in production and trade of fishery products. Most of the
      current quality control techniques are time consuming and cumbersome. There is an
      excellent scope for the application of biosensors in the seafood industry
      including the rapidly expanding aquaculture operations for fast assessment of
      quality. This article discusses the scope of applications biosensors in the
      seafood industry.

PMID- 11839469
TI  - Signaling of transcriptional chemistry in the on-line detection format.
AB  - A critical analysis of optical and acoustic wave instrumentation for examining
      the transcription apparatus and its regulation is given in the present review.
      The physico-chemical parameters derived from such in vitro experiments are
      important from a biophysical standpoint. The overall mechanism of transcription
      is composed of several mechanisms such as DNA-binding and promoter selection,
      closed and open polymerase complex formation, initiation of RNA synthesis,
      elongation and termination. Surface plasmon resonance (SPR) and fluorescence
      spectroscopy are widely employed techniques for investigating these mechanisms in
      real time. Although the binding of nucleotides, transcription factors (TFs) and
      inhibitors to RNA polymerase (RNAP) and the DNA template have been studied
      extensively, the synthesis of mRNA has not been investigated in detail except by
      methods based on electrophoresis. The use of acoustic wave physics for
      investigating transcriptional chemistry offers not only a time-course analysis
      but also the potential to gain insight into structural changes that occur during
      the process.

PMID- 11839470
TI  - A novel ISFET-type biosensor based on P450 monooxygenases.
AB  - We made a biosensor based on ion-sensitive field effect transistor (ISFET) using
      P450 monooxygenase. ISFETs are electrical devices and have been used as pH
      sensors. We used genetically engineered P450 monooxygenase for our research
      because of its high enzymatic activity. The fusion enzyme between rat CYP1A1P450
      monooxygenase and yeast NADPH-cytochrome P450 oxidoreductase was expressed in
      yeast Saccharomyces cerevisiae strain AH22. Yeast microsomal membranes were
      immobilized in an agarose layer on the ISFET. o-Deethylation of 7-ethoxycoumarin
      to 7-hydroxycoumarin was catalyzed by the enzyme in the presence of nicotinamide
      adenine dinucleotide phosphate reduced form (NADPH). Formation of 7
      hydroxycoumarin from 7-ethoxycoumarin was also measured by fluorescence. The
      difference of the voltage between the ISFET device and control device without
      enzymes showed a voltage increase along with the enzymatic reaction of P450
      monooxygenases, and this voltage increase in the device was inhibited by addition
      of MnCl(2), an inhibitor of P450 monooxygenase. There was a positive correlation
      between the voltage increase in the ISFET device and the fluorescence intensity.
      This is the first electrochemical biosensing using P450 monooxygenases
      immobilized on the ISFET, and is applicable to the sensing of chlorophenol
      compounds.

PMID- 11839471
TI  - A new amperometric glucose microsensor: in vitro and short-term in vivo
      evaluation.
AB  - For biosensor fabrication, it is important to optimize materials and methods in
      order to create predictable function in vitro and in vivo. For this reason, we
      designed a new glucose sensor ('revised protocol') that utilized an outer
      permselective membrane made of amphiphobic polyurethane which allows glucose
      passage through hydrophilic segments. An inner polyethersulfone membrane,
      stabilized with a trimethoxysilane, provided specificity. Before application of
      the inner membrane, it was necessary to etch the platinum electrode with a radio
      frequency oxygen plasma. The revised protocol sensors (n=185) were compared with
      sensors fabricated with an earlier ('original') protocol (n=204) which used an
      outer polyurethane without hydrophilic segments and a complex inner membrane of
      cellulose acetate and Nafion. The function of revised protocol sensors was more
      predictable in vitro as evidenced by a much lower variation of glucose
      sensitivity than the original protocol sensors. Revised and original protocol
      sensors were nearly linear up to a glucose concentration of 20 mM. In vitro
      interference from 0.1 mM acetaminophen was minimal in both groups of sensors and
      would be expected to represent about 2% of the total sensor response at normal
      glucose levels for revised protocol sensors. Prolonged testing of the revised
      protocol sensors for 11 days during immersion in buffer revealed stable
      sensitivities (day 1: 6.12+/-1.34 nA/mM; day 3: 6.33+/-1.40; day 8: 7.13+/-1.39;
      and day 11: 7.56+/-1.47; sensitivity for day 1 vs. each other day: not
      significant) and no critical loss of glucose oxidase activity. The response of
      the revised protocol sensors (n=7) to intraperitoneal glucose was tested in rats
      approximately one day after subcutaneous implantation and the sensors tracked
      glucose closely with a slight lag of 3-6 min.

PMID- 11839472
TI  - Amperometric biosensor based on a functionalized gold electrode for the detection
      of antioxidants.
AB  - A method for the electrochemical detection of antioxidants has been developed,
      which is based on a radical measurement with a cytochrome c modified electrode. A
      controlled enzymatic production system for superoxide radicals based on xanthine
      oxidase was used. The addition of antioxidants facilitated the decomposition of
      the radical in addition to the spontaneous dismutation. The steady-state of
      superoxide generation and decomposition was thus shifted to a new situation due
      to the higher decomposition rate after antioxidant addition. This resulted in a
      decreased current level at the electrode. Antioxidant activity could be
      quantified from the response of the sensor electrode by the percentage of the
      signal decrease. The 50% inhibition value (IC(50)) for different antioxidants was
      calculated and the antioxidant activity of numerous substances was compared.
      Thus, a hierarchy of superoxide radical scavenging abilities of flavonoids was
      established: flavanols>flavonols>flavones>flavonones>isoflavonones.

PMID- 11839473
TI  - Characterisation of an antibody coated microcantilever as a potential immuno
      based biosensor.
AB  - In this study, we investigated the activity, stability, lifetime and re-usability
      of monoclonal antibodies to myoglobin covalently immobilised onto microfabricated
      cantilever surfaces. These sensing surfaces are of interest to us in the
      development of novel cantilever-based immunosensors. For such sensors the
      antibody layer represents the sensing element while the microcantilever acts as a
      mechanical transducer. A procedure for producing re-usable biological coatings
      has been tested with different independent techniques. An Enzyme Linked
      Immunosorbent Assay (ELISA) was used to determine the presence of an active
      antibody coating, and to monitor the lifetime and stability of the immobilised
      antibody. Through this analysis, the activity of the immobilised antibody layer
      was found to be more stable with the introduction of sucrose, as a stabilising
      agent. Sucrose was applied to the immobilised antibody layer after each
      regeneration step. The immobilised antibody was found to have a stable active
      lifetime for up to 7 weeks. Fluorescence microscopy was used to give information
      on the distribution of the coating on the gold and silicon nitride sides of the
      cantilever. Atomic Force Microscopy was used to determine the presence of the
      biological coating on the cantilever and to obtain information on the surface
      morphology of the biological element of the sensor. The combined results provide
      valuable information on the development of an optimised sensing element and
      demonstrate a set of methods to use for future sensor-to-sensor characterisation.
      Preliminary experimental results showing the antibody activity against myoglobin,
      detected with a microcantilever based sensor prototype confirmed the motivations
      and potentialities of the proposed immunosensing technique.

PMID- 11839474
TI  - Cellular biosensing system for discovery of protein synthesis inhibitors with an
      electrochemical phosphate modulator to regulate the acid phosphatase gene
      expression of Saccharomyces cerevisiae.
AB  - A cellular biosensing system for screening protein synthesis inhibitors has been
      developed by linking an electrochemical phosphate modulator and matrix
      immobilized yeast cells with an optical sensing device. To screen the protein
      synthesis inhibitors, yeast phosphatase gene regulating system has been employed
      by linking an electrochemical phosphate modulator. Since the yeast phosphatase
      gene coding gammaAPase is expressed, when the phosphate concentration in solution
      is lowered below the threshold, the gammaAPase production is triggered by
      lowering the phosphate concentration with the electrochemical phosphate
      modulator, and monitored continuously with the photometric device. The
      electrochemical phosphate modulator was assembled with matrix-immobilized yeast
      cells. The module could insert to ordinal cuvette to monitor the induced
      gammaAPase activity in an ordinal photometer. Using the system, induction profile
      of protein synthesis was easily observed and was affected remarkably by various
      protein synthesis inhibitors. This seems promising that the system can be applied
      for first screening process of de novo protein inhibitors. The cellular
      biosensing system seems promising in screening protein synthesis inhibitors.

PMID- 11839475
TI  - Composite electrochemical biosensors: a comparison of three different electrode
      matrices for the construction of amperometric tyrosinase biosensors.
AB  - A comparison of the behaviour of three different rigid composite matrices for the
      construction of amperometric tyrosinase biosensors, which are widely used for the
      detection of phenolic compounds, is reported. The composite electrode matrices
      were, graphite-Teflon; reticulated vitreous carbon (RVC)-epoxy resin; and
      graphite-ethylene/propylene/diene (EPD) terpolymer. After optimization of the
      experimental conditions, different aspects regarding the stability of the three
      composite tyrosinase electrode designs were considered and compared. A better
      reproducibility of the amperometric responses was found with the graphite-EPD
      electrodes, whereas a longer useful lifetime was observed for the graphite-Teflon
      electrodes. The kinetic parameters of the tyrosinase reaction were calculated for
      eight different phenolic compounds, as well as their corresponding calibration
      plots. The general trend in sensitivity was graphite-EPD>graphite-Teflon>>RVC
      epoxy resin. A correlation between sensitivity and the catalytic efficiency of
      the enzyme reaction for each phenolic substrate was found. Furthermore,
      differences in the sensitivity order for the phenolic compounds were observed
      among the three biocomposite electrodes, which suggests that the nature of the
      electrode matrix influences the interactions in the tyrosinase catalytic cycle.

PMID- 11839476
TI  - Photoinduced kinetics of bacteriorhodopsin in a dried xerogel glass.
AB  - Time-resolved absorption measurements of the formation and decay kinetics of the
      M (deprotonated) photocycle intermediate of bR purple membranes entrapped within
      a dried xerogel glass have been investigated. The dramatic change observed for
      the M state decay time is in contrast to the relatively insensitive half life
      reported for the M intermediate of the D96N mutant entrapped within a dried sol
      gel glass. The decay kinetics of the M intermediate was observed to slow by a
      factor of almost 100 when the solvent was removed from the wet-gel to form the
      dry xerogel glass. Very long aging times for wet-gels resulted in highly
      biexponential M state decay kinetics. Upon drying, the M state formation rate
      initially decreased relative to that in solution before increasing in the dry
      xerogel to a formation rate nearly three times faster than in solution.

PMID- 11839477
TI  - Photochemical properties of a riboflavins/cytochrome P450 2B4 complex.
AB  - The present study demonstrates the possible use of a non-covalent complex of
      riboflavins with cytochrome P450 2B4 (artificial flavocytochrome P450 2B4) for
      photo-induced intermolecular electron transfer between the isoalloxazine cycle of
      flavins and the ferric heme group of cytochrome P450 2B4. Riboflavin was used as
      a light-induced electron donor for the transfer of electrons to cytochrome P450.
      The quantitative measurement of the photocurrent, generated by photoreduction of
      non-covalent flavocytochrome P450 2B4, was carried out. In the presence of
      typical substrates for cytochrome P450 2B4 the decrease of cathodic photocurrent
      occurred, generated not only by riboflavin itself but also by a
      riboflavin/cytochrome P450 complex. It was demonstrated that flavocytochromes
      might serve as molecular amplifiers of a photocurrent, generated upon flavins'
      reduction. Introduction of flavin residues into the cytochrome P450 molecule
      transformed this haemoprotein into a photoreceptor and a photodiode and, in
      addition, into a photosensitive and photo-activated enzyme.

PMID- 11839478
TI  - Engineering receptors and antibodies for biosensors.
AB  - Biosensor sensitivity and selectivity depend essentially on the properties of the
      biorecognition elements to be used for analyte binding. Two principally different
      applications are considered, (1) effects monitoring with biological components as
      targets for bioeffective substances, among them endocrine disruptors; and (2)
      immunochemical analysis employing antibodies as binding proteins for a wide
      variety of analytes such as pesticides. Genetic engineering provides an elegant
      way not only for providing unlimited amounts of biorecognition molecules but also
      for the alteration of existing properties and the supplementation with additional
      functions. Instrumental applications were carried out with the optical sensor
      BIAcore. The first example deals with the characterization of receptors. For this
      purpose, the human estrogen receptor alpha was used. Binding studies were carried
      out with natural as well as xenoestrogens. An equilibrium dissociation constant
      K(d) of 2.3x10(-10) (M) was derived for 17beta-estradiol. A competition assay was
      performed with a bovine serum albumin (BSA)-17beta-estradiol conjugate,
      immobilized at the optical sensor surface, and the free estrogen. The signals
      obtained represent estradiol equivalents. This format was transferred to a
      microplate-based enzyme-linked receptor assay. It reached a detection limit of
      0.02 microg l(-1) 17beta-estradiol and proved suitable for the detection of
      natural and synthetic estrogens as well as xenoestrogens in field studies. The
      second example is targeted at kinetic and affinity measurements of recombinant
      antibody fragments derived from antibody libraries with s-triazine selectivities.
      Different strategies for the synthesis of antibody fragment libraries, followed
      by the selection of specific antibody variants, were examined. An antibody
      library was derived from a set of B cells. Chain shuffling of the heavy and light
      chains provided the best binders. An enzyme linked immunosorbent assay (ELISA)
      was achieved for atrazine with an IC(50) of 0.9 microg l(-1) and a detection
      limit of 0.2 microg l(-1). The close relations between the optimization of
      recombinant antibodies by evolutionary strategies and genetic algorithms are
      considered.

PMID- 11839479
TI  - Glucose sensor using a microfabricated electrode and electropolymerized bilayer
      films.
AB  - A new type miniaturized glucose sensor with good selectivity and stable current
      response has been developed. The structure consists of a recessed rectangular
      microfabricated platinum electrode, inner layer of two electropolymerized
      nonconducting films, and outer bilayer of poly(tetrafluoroethylene) (Teflon) and
      polyurethane (PU) films. Glucose oxidase (GOx) is entrapped during the
      electropolymerization of a poly(m-phenylenediamine) (PMPD) film in an acetate
      buffer (AB) solution, on which a highly interference-resistive PMPD film is
      deposited in a phosphate buffered saline (PBS) solution. The second PMPD film
      causes no significant decrease in accessibility of glucose to GOx. The inner
      layer maintains less than 1% permeability to acetaminophen for 12 days. The
      fairly adhesive outer layer allows stable current response. Due to high
      permeability, the information about enzyme activity can be obtained without
      serious error in spite of outer layer intervening between enzymes and solution.
      The apparent Michaelis-Menten constant and the maximum steady-state current
      density were 24 mM and 80 microA cm(-2), respectively.

PMID- 11839484
TI  - Unraveling hot spots in binding interfaces: progress and challenges.
AB  - Protein interface hot spots, as revealed by alanine scanning mutagenesis,
      continue to stimulate interest in the biophysical basis of molecular recognition.
      Although these regions apparently constitute fertile grounds for intermolecular
      interactions, no general algorithm has yet been developed that can predict hot
      spots based solely on their shape or composition. The discovery of structural
      plasticity in hot spot regions indicates that dynamic simulation techniques may
      be essential for achieving a predictive understanding of binding interface
      energetics. Future progress will depend as much on the application of new
      computational approaches for dissecting protein interfaces as on expanding our
      empirical databank of mutagenic substitutions and their effects. Despite our
      current theoretical shortcomings, recent methodological advances provide
      efficient experimental means of probing hot spots and enable immediate
      applications for hot spots in drug discovery.

PMID- 11839485
TI  - Evolutionary predictions of binding surfaces and interactions.
AB  - Rapid progress in structural biology and whole-genome sequencing technology means
      that, for many protein families, structural and evolutionary information are
      readily available. Recent developments demonstrate how this information can be
      integrated to identify canonical determinants of protein structure and function.
      Among these determinants, those residues that are on protein surfaces are
      especially likely to form binding sites and are the logical choice for further
      mutational analysis and drug targeting.

PMID- 11839486
TI  - Prediction of protein-protein interactions by docking methods.
AB  - Recently, developments have been made in predicting the structure of docked
      complexes when the coordinates of the components are known. The process generally
      consists of a stage during which the components are combined rigidly and then a
      refinement stage. Several rapid new algorithms have been introduced in the rigid
      docking problem and promising refinement techniques have been developed, based on
      modified molecular mechanics force fields and empirical measures of desolvation,
      combined with minimisations that switch on the short-range interactions
      gradually. There has also been progress in developing a benchmark set of targets
      for docking and a blind trial, similar to the trials of protein structure
      prediction, has taken place.

PMID- 11839487
TI  - Protein-protein association kinetics and protein docking.
AB  - Rigid body protein docking methods frequently yield false positive structures
      that have good surface complementarity, but are far from the native complex. The
      main reason for this is the uncertainty of the protein structures to be docked,
      including the positions of solvent-exposed sidechains. Substantial efforts have
      been devoted to finding near-native structures by rescoring the docked
      conformations and employing various filters. An alternative approach emulates the
      process of protein-protein association, that is, first finding the region in
      which binding is likely to occur and then refining the complex while allowing for
      flexibility.

PMID- 11839488
TI  - Kinetic studies of protein-protein interactions.
AB  - The structure of a protein-protein interaction, its affinity and thermodynamic
      characteristics depict a 'frozen' state of a complex. This picture ignores the
      kinetic nature of complex formation and dissociation, which are of major
      biological and biophysical interest. This review highlights recent advances in
      deciphering the kinetic pathway of protein-protein complexation, the nature of
      the encounter complex, transition state and intermediate along the reaction, and
      the effects of mutation, viscosity, pH and salt on association.

PMID- 11839489
TI  - Protein folding and three-dimensional domain swapping: a strained relationship?
AB  - Many proteins function as multimeric assemblies into which the folded individual
      promoters organize as higher order structures. An oligomerization mechanism that
      appears to impose the coordination of events during folding and oligomer assembly
      is three-dimensional domain swapping. Recent studies have focused on revealing
      the structural basis of domain swapping and a possible role for domain swapping
      in the regulation of protein aggregation and activity.

PMID- 11839490
TI  - Coupling of folding and binding for unstructured proteins.
AB  - There are now numerous examples of proteins that are unstructured or only
      partially structured under physiological conditions and yet are nevertheless
      functional. Such proteins are especially prevalent in eukaryotes. In many cases,
      intrinsically disordered proteins adopt folded structures upon binding to their
      biological targets. Many new examples of coupled folding and binding events have
      been reported recently, providing new insights into mechanisms of molecular
      recognition.

PMID- 11839491
TI  - The modular logic of signaling proteins: building allosteric switches from simple
      binding domains.
AB  - Many eukaryotic signal transduction proteins have component-based architectures:
      they are built from combinations of protein interaction domains and catalytic
      domains. Intact, these proteins display the sophisticated allosteric behavior
      required for cellular regulation; the protein's output activity is tightly
      repressed under basal conditions, but can be robustly activated by a specific set
      of input effector ligands. A combination of structural, biophysical and
      computational studies is beginning to shed light on the fundamental principles
      governing this type of modular allostery.

PMID- 11839493
TI  - Towards the structure of the mammalian signal recognition particle.
AB  - The signal recognition particle (SRP) is a ubiquitous ribonucleoprotein particle
      involved in the co-translational targeting of proteins to membranes. Crystal
      structures are now available for three protein-RNA subcomplexes from the SRP,
      which give insights into fundamental aspects of protein-RNA recognition, the
      assembly of stable ribonucleoprotein particles and the mechanism of action of the
      SRP.

PMID- 11839494
TI  - Poly(A) tail synthesis and regulation: recent structural insights.
AB  - Polyadenylation at the 3' ends of mRNAs is critical to the translation and
      stability of the messages. Recently determined structures of poly(A) polymerase,
      U1A and domains of the poly(A)-binding protein provide a framework for
      understanding the synthesis and regulation of the poly(A) tail.

PMID- 11839495
TI  - Multisubunit RNA polymerases.
AB  - Transcription of the genetic information in all cells is carried out by
      multisubunit RNA polymerases (RNAPs). Comparison of the crystal structures of a
      bacterial and a eukaryotic RNAP reveals a conserved core that comprises the
      active site and a multifunctional clamp. Together with a further structure of
      eukaryotic RNAP bound to DNA and RNA, these results elucidate many aspects of the
      transcription mechanism, including initiation, elongation, nucleotide addition,
      processivity and proofreading.

PMID- 11839497
TI  - Eukaryotic transcription factors.
AB  - Recently determined high-resolution structures of eukaryotic transcription
      factors have illuminated the enzymatic mechanism underlying transcription.
      Progress has been made in characterising protein-protein interactions between
      negative cofactors and general transcription factors, and between transrepression
      domains and corepressors. Structures of sequence-specific transcription factors
      have revealed further versatility in the mode of interaction with DNA and several
      have provided new insights into the molecular basis of human disease.

PMID- 11839496
TI  - Prokaryotic transcription regulators: more than just the helix-turn-helix motif.
AB  - Over the past two years, the structures of many prokaryotic transcriptional
      regulators have been solved, and several of them have revealed the structural
      mechanism of gene regulation. The crystal structure of BmrR-TPP-DNA reveals a
      novel mechanism of transcription activation, whereby the drug-bound protein
      activates the bmr promoter by local DNA unwinding and base pair disruption.
      Myristoyl-CoA induces FadR by a three-helix pushing mechanism, whereas TetR
      employs a helical pendulum motion to regulate expression. The structures of AbrB,
      and DNA complexes of Rob and MuR unveil a novel DNA-binding motif, 'the looped
      hinge helix', and new uses of the helix-turn-helix and winged helix motifs in DNA
      binding.

PMID- 11839498
TI  - DNA double-strand break repair from head to tail.
AB  - DNA double-strand break repair is a complex process that requires multiple
      enzymatic and structural activities to rejoin or repair the broken DNA ends using
      one of several repair pathways. These enzymatic and structural activities include
      end detection, end processing and alignment of DNA ends. Recent structural and
      functional studies of the DNA double-strand break repair factors Mre11/Rad50,
      Ku70/80 and Xrcc4 show how these enzymes combine and assemble both enzymatic and
      structural activities in DNA double-strand break repair.

PMID- 11839499
TI  - Helicase structure and mechanism.
AB  - Structural information on helicase proteins has expanded recently beyond the DNA
      helicases Rep and PcrA, and the hepatitis C virus RNA helicase to include UvrB,
      members of the DEA(D/H)-box RNA helicase family, examples of DnaB-related
      helicases and RuvB. The expanding database of structures has clarified the
      structural 'theme and variations' that relate the different helicase families.
      Furthermore, information is emerging on the functions of the conserved helicase
      motifs and their participation in the mechanisms by which these proteins catalyze
      the remodeling of DNA and RNA in ATP-dependent activities.

PMID- 11839501
TI  - The embryonic-like properties of aggressive human tumor cells.
AB  - During embryogenesis, the formation and remodeling of primary vascular networks
      occur by vasculogenesis and angiogenesis. Recently, the term "vasculogenic
      mimicry" was introduced by our laboratory and collaborators to reflect the
      embryonic-like ability of aggressive, but not nonaggressive, tumor cells to form
      a pattern of vasculogenic-like networks in three-dimensional culture, with
      concomitant expression of vascular-associated cell markers. We reviewed research
      on the ability of invasive ovarian carcinoma cells to engage in molecular
      vasculogenic mimicry reflected by their plasticity. In addition, we reviewed in
      vivo evidence regarding the presence of tumor cell-lined vasculature in
      aggressive ovarian carcinoma and other cancers, which may serve as the correlate
      to in vitro vasculogenic mimicry. These results may offer new insights and
      molecular markers for consideration in ovarian cancer diagnosis and treatment
      strategies based on molecular vascular mimicry by aggressive tumor cells.

PMID- 11839503
TI  - Production of oxytocin receptor and cytokines in primary uterine smooth muscle
      cells cultivated under inflammatory conditions.
AB  - OBJECTIVE: We studied the production of the oxytocin receptor and interleukins in
      human uterine smooth muscle cells cultured in vitro in the presence of cytokines
      that were shown to be elevated in gestational diseases such as intrauterine
      infections and chorioamnionitis. METHODS: Human uterine smooth muscle cells were
      cultured in the absence or presence of interleukin-1beta (IL-1beta), interleukin
      6 (IL-6), tumor necrosis factor alpha (TNFalpha), or lipopolysaccharide (LPS).
      Additionally, cells were cultivated under hypoxic conditions (3.5% oxygen). After
      6, 12, 24, and 48 hours of incubation, oxytocin receptor mRNA was measured from
      total RNA using quantitative, competitive reverse transcriptase-polymerase chain
      reaction. Secreted cytokines (IL-1beta, IL-6, or IL-8) were quantitated from
      supernatants after 6, 12, 24, and 48 hours of stimulation by commercially
      available enzyme-linked immunosorbent assay. RESULTS: In nonstimulated cultures
      basal secretion of IL-1beta, IL-6, and IL-8 was detectable. Supplementation of IL
      1beta induced a statistically significant decrease in oxytocin receptor mRNA
      abundance, whereas IL-6, TNFalpha, LPS, or hypoxia did not significantly affect
      oxytocin receptor gene expression. The cytokines IL-1 and TNFalpha induced IL-6
      and IL-8 release, whereas secretion of the two interleukins was not altered in
      the presence of LPS or hypoxia. Expression of IL-1beta was not significantly
      induced under inflammatory or hypoxic culture conditions. CONCLUSION: The
      constitutive and cytokine-inducible expression of interleukins from uterine
      smooth muscle cells suggests that the myometrium may contribute to the overall
      production of inflammatory mediators in the uterus that are thought to govern
      term- or infection-induced preterm labor. Down-regulation of the oxytocin
      receptor under IL-1beta in myometrial cells may indicate that initiation and
      maintenance of labor could be partially limited under severe inflammatory
      conditions such as chorioamnionitis.

PMID- 11839502
TI  - Intrahepatic cholestasis of pregnancy: an intriguing pregnancy-specific disorder.
AB  - OBJECTIVE: To review animal and human data available regarding the etiology,
      maternal and fetal impact, and treatment of intrahepatic cholestasis of pregnancy
      (ICP). METHODS: Pertinent studies on human and animal models of ICP were selected
      through a MEDLINE database search, focusing on etiology and clinical impact of
      the disease. Analytic and descriptive studies were included, and the data were
      analyzed looking for crude numbers. RESULTS: Intrahepatic cholestasis of
      pregnancy is a pregnancy-specific disorder. Its prevalence is higher in Chile and
      Sweden compared with any other population. Its etiology is largely unknown,
      although endocrine, genetic, and environmental factors have been postulated as
      responsible for the appearance of the disease. Maternal effects of ICP are mild;
      however, there is a clear association between ICP and poor perinatal outcome,
      including a higher frequency of fetal distress, preterm labor and delivery, and
      unexplained fetal death. The treatment is mainly symptomatic. Recent data suggest
      that oral use of ursodeoxycholic acid improves maternal condition and might
      prevent the fetal complications of ICP. CONCLUSIONS: Intrahepatic cholestasis of
      pregnancy should be considered a high-risk condition, and careful fetal
      assessment and appropriate medical intervention might improve perinatal outcome.

PMID- 11839504
TI  - Shiga toxin 1 and 2 induce apoptosis in the amniotic cell line WISH.
AB  - OBJECTIVE: The aim of this study was to evaluate the toxicity of Shiga toxin
      (Stx) 1 and 2 on amniotic cells in vitro. METHODS: WISH cells, which were derived
      from human amniotic cells, and Vero cells were cultured with or without Stxs.
      After 24 hours of culture, cell viability was measured by Cell Counting Kit-8,
      and extracted DNA was electrophoresed on a 1% agarose gel. The morphologic
      changes were observed by Papanicolaou staining, and the apoptotic index
      (percentage of apoptotic nuclei per total nuclei) was calculated. Quantification
      of apoptotic cells was also measured by an enzyme-linked immunosorbent assay.
      RESULTS: The viability of WISH cells decreased in proportion to the
      concentrations of Stxs. Cellular ladder formation was observed by DNA
      electrophoresis of Stx-treated WISH cells, and the typical morphologic changes
      were observed by Papanicolaou staining. The proportion of apoptotic cells
      increased in response to Stxs. CONCLUSIONS: Stxs injured WISH cells directly and
      induced apoptosis in vitro. WISH cells were as sensitive as Vero cells to Stxs
      and cell death occurred by apoptosis.

PMID- 11839505
TI  - The effects of photoperiod on the switching of myometrial contractility patterns
      of pregnant baboons: relationship to surgery and parturition.
AB  - OBJECTIVES: Pregnant baboons were studied to determine the precise time of the
      switch from myometrial contractures to contractions in relation to photoperiod
      after laparotomy and at parturition. We compared the patterns recorded in baboons
      to those we have previously reported in pregnant rhesus monkeys to determine
      fundamental primate characteristics. METHODS: Seven pregnant baboons (126-160
      days' gestation) were instrumented with femoral arterial and venous catheters and
      electrodes for myometrial electromyogram. All animals were subjected to a 14-hour
      light:10-hour dark photoperiod. Myometrial activity was monitored using a
      computer-based data acquisition system. Onset time for all switches was noted and
      standardized against time of lights off. Animals were studied at three stages of
      pregnancy (stage 1, first 10 days after laparotomy; stage 2, more than 10 days
      after laparotomy and more than 10 days before cesarean; and stage 3, 10 days
      before cesarean section or vaginal delivery). RESULTS: All baboons demonstrated
      myometrial switches for a variable number of days preceding parturition. Onset of
      darkness was 0 hours. Average time of stage 1 switch onset was 2.17 +/- 0.60
      hours and was not different from stage 3 switch onset, which was -1.00 +/- 0.27
      hours. CONCLUSIONS: Myometrial contractile patterns showed clear photoperiodicity
      in the switch from contractures to contractions in late pregnancy in the baboon.
      The relationship of the switch from contractures to contractions was not altered
      by surgical laparotomy. There was a significant difference in the time of switch
      in relation to photoperiod between pregnant rhesus monkeys and baboons. However,
      the fact that a significant photoperiod exists in both species indicates a
      fundamental similarity in the switch from contractures to contractions in primate
      pregnancy.

PMID- 11839506
TI  - High levels of human chromogranin A in umbilical cord plasma and amniotic fluid
      at parturition.
AB  - OBJECTIVE: The human placenta is a neuroendocrine organ that produces several
      hypothalamic and pituitary hormones that are secreted during pregnancy and
      parturition into maternal and fetal circulation and amniotic fluid. Human
      chromogranin A (CgA) is a glycoprotein mainly localized to the adrenal medulla
      and released in response to several stressful events. During pregnancy,
      intrauterine tissues express and synthesize CgA mRNA and peptide and secret it
      into the biologic fluids of pregnancy, so we investigated whether maternal,
      umbilical, and amniotic human CgA levels are affected by the stress of
      parturition. METHODS: We measured pregnancy CgA levels in maternal and umbilical
      cord plasma and in amniotic fluid at term (39-40 weeks), by enzyme-linked
      immunosorbent assay at elective cesarean (n = 16), after spontaneous vaginal
      delivery (n = 12), and longitudinally throughout labor and 2 hours postpartum.
      RESULTS: CgA levels were highest in umbilical cord blood (P <.001). Umbilical
      cord plasma and amniotic fluid CgA levels were significantly higher at
      spontaneous vaginal delivery than at cesarean (P <.001), and the levels were not
      changed in maternal plasma according to cervical dilatation and postpartum.
      CONCLUSIONS: The present findings showed that the stress of parturition increased
      CgA levels in umbilical cord plasma and amniotic fluid and was probably of fetal
      origin. Whatever the mode of delivery, CgA levels in infants were much more
      elevated than in mothers, providing evidence for an unusual and sustained high
      level of sympathoadrenal stimulation in full-term neonates.

PMID- 11839507
TI  - Use of magnetic resonance imaging and ultrasound in the antenatal diagnosis of
      placenta accreta.
AB  - OBJECTIVE: To determine whether magnetic resonance imaging (MRI) and ultrasound
      (US) are effective methods for diagnosing placenta accreta, increta, or percreta
      antenatally. METHODS: We retrospectively reviewed radiologic reports of patients
      who had the diagnosis of placenta accreta, percreta, or increta by pathologic
      analysis. The gestational age at first ultrasound diagnosis of accreta and first
      MRI diagnosis of accreta was recorded. Ultrasound and MRI reports were examined
      for findings of a distorted retroplacental myometrial zone, disrupted uterine
      bladder interface, focal exophytic masses, and presence of vascular placental
      lacunae. Surgical history, cesarean hysterectomy, and blood loss were also
      recorded. RESULTS: Thirteen patients were identified, and 14 had true pathologic
      confirmation of accreta, increta, or percreta. Nine of thirteen had MRI, and of
      those, seven received gadolinium. Placenta accreta was diagnosed by MRI in five
      of nine patients, but only four were confirmed pathologically to have accreta.
      Four women who had a normal MRI had accreta confirmed by pathology (sensitivity
      38%). Of the 13 patients who had US, four were considered to have an accreta, and
      these four had pathologic confirmation. Nine were negative for accreta by US;
      however, eight of those women had pathologic confirmation of accreta, and one was
      normal (sensitivity 33%). CONCLUSION: Both MRI and US had poor predictive value
      in the diagnosis of placenta accreta, and further refinement in the techniques of
      both MRI and US is needed for these tests to be used to reliably diagnose these
      pathologic conditions.

PMID- 11839508
TI  - Characterization of cyclin D2 expression in human endometrium.
AB  - OBJECTIVE: This study was undertaken to investigate cyclin D2 mRNA and protein
      expression in human endometrium during the menstrual cycle. METHODS: Endometrial
      samples were obtained from 15 premenopausal nonpregnant women who had
      hysterectomies for benign gynecologic reasons. They were divided into the
      following five groups according to histologic dating: early proliferative (n =
      3), mid to late proliferative (n = 3), early secretory (n = 3), mid secretory (n
      = 3), and late secretory (n = 3). Cyclin D2 mRNA and protein expression were
      analyzed using reverse transcriptase-polymerase chain reaction, Western blotting,
      and immunohistochemistry. RESULTS: Cyclin D2 mRNA and protein were expressed in
      human endometrial tissue throughout the menstrual cycle. Cyclin D2 mRNA and
      protein expression of proliferative phase endometrium were significantly higher
      than those of secretory phase endometrium (P <.05). The staining intensity of
      cyclin D2 in proliferative phase endometrium was higher than that in secretory
      phase (P <.05). Cyclin D2 mRNA level showed good correlation with cyclin D2
      protein level (R = 0.579, P <.03), and cyclin D2 protein also showed good
      correlation with immunohistochemical staining intensity (R = 0.562, P <.03).
      CONCLUSION: Cyclin D2 was expressed in human endometrium throughout the menstrual
      cycle. Cyclin D2 mRNA and protein were expressed at high levels in proliferative
      phase endometrium, especially in the early proliferative phase, and then
      decreased in the secretory phase.

PMID- 11839509
TI  - Pelvic nerve plexus trauma at radical and simple hysterectomy: a quantitative
      study of nerve types in the uterine supporting ligaments.
AB  - OBJECTIVE: Using neuropeptide and enzyme markers to autonomic nerves, we sought
      to demonstrate and quantify the nerve types contained within the uterosacral
      ligaments (USLs) and cardinal ligaments (CLs) that are divided during radical
      hysterectomy (RH). METHODS: Cross-sectional biopsies were collected from the
      lateral third of the USL and the CL in 24 women who had an RH for cervical
      cancer, and from the uterine insertion of these ligaments in 11 women who had a
      simple hysterectomy for benign disease. We applied indirect immunofluorescence
      with FITC-conjugated secondary antibodies, using polyclonal primary antibodies to
      neuropeptide markers that predominate within somatic and autonomic nerves, to
      show different populations of the following nerve types within the biopsies:
      neuropeptide Y (NPY) and tyrosine hydroxylase (TH) for sympathetic nerves;
      vasoactive intestinal polypeptide (VIP) for parasympathetic nerves; substance P
      (SP) for nociceptive and sensory-motor nerves; and calcitonin gene-related
      peptide (CGRP) for sensory and sensory-motor nerves. The percentage area of
      immunoreactivity (PAI), determined by a computer-assisted image analyzer attached
      to a fluorescent microscope, was used as an objective quantitative measure of
      nerve density. Confocal microscopy was used to determine the composition and
      spatial arrangement of nerve fibers in the ligaments. RESULTS: The PAI was
      greater for all markers tested in both the USL and CL (P <.001) in RH compared
      with simple hysterectomy biopsies. For RH specimens, the PAI was greater for the
      sympathetic, sensory, and sensory-motor nerve markers in the USL compared with
      the CL (P <.01), but the PAI for VIP was similar (P >.05). Conversely, excluding
      the large trunks and associated ganglia, the free nerve fiber PAI in the CL was
      greater than that of the USL for all nerve markers (P <.001). The staining of
      peripheral autonomic ganglia and associated fibers, for NPY and TH, indicates
      that some sympathetic nerves are preganglionic with their cell bodies within the
      pelvic plexus. CONCLUSIONS: Significantly more autonomic nerves are transected in
      the more lateral division of the uterine supporting ligaments during a radical
      hysterectomy than during a simple hysterectomy. Sympathetic, parasympathetic,
      sensory, and sensory-motor nerve types are present within the CL and USL. The
      proportions of each nerve type differ between the two ligaments, and sympathetic
      nerves in the USL are the single largest nerve type. The uterine supporting
      ligaments are a major pathway for autonomic nerves to the pelvic organs.

PMID- 11839511
TI  - New vaccines: damming for multi-strain organisms?

PMID- 11839510
TI  - VEGF therapy in heart disease: for better or for worse?

PMID- 11839512
TI  - Electronic DPI for insulin.

PMID- 11839513
TI  - New promises for schizophrenia therapy.

PMID- 11839516
TI  - William Pardridge discusses the lack of BBB research. Interview by Rebecca N.
      Lawrence.

PMID- 11839517
TI  - Ion channel screening technologies: will they revolutionize drug discovery?

PMID- 11839518
TI  - The utility of predictivity in drug discovery and use.

PMID- 11839519
TI  - Evaluating R&D projects and portfolios.

PMID- 11839520
TI  - Safety pharmacology for the non-clinical assessment of medicinal products.

PMID- 11839521
TI  - Target validation of G-protein coupled receptors.
AB  - G-protein coupled receptors (GPCRs) represent possibly the most important target
      class of proteins for drug discovery. Over 30% of clinically marketed drugs are
      active at this receptor family. These drugs exhibit their activity at <10% of all
      known GPCRs. A major challenge for the pharmaceutical industry is to associate
      the many novel GPCRs with disease to identify the drugs of the future. This
      process consists of a collection of experimental paradigms that together can be
      loosely labelled 'target validation'.

PMID- 11839522
TI  - Bacterial toxins as tools for mucosal vaccination.
AB  - Several studies have demonstrated that the biological properties of secreted
      bacterial toxins could be harnessed for the induction of mucosal and systemic
      immunity following application at epithelial surfaces. Although the properties
      and potential application of several of these toxins will be discussed in this
      review, special focus will be placed on Pseudomonas aeruginosa exotoxin A (PE). A
      non-toxic form of PE (ntPE) into which antigenic epitopes can be integrated
      appears to be a particularly promising vaccination tool, which is able to cross
      the polarized epithelia of the gastrointestinal, respiratory and reproductive
      tracts and selectively target macrophages and dendritic cells.

PMID- 11839523
TI  - Glutamate receptors and persistent pain: targeting forebrain NR2B subunits.
AB  - Glutamate is the fast excitatory transmitter in mammalian brains. It binds to two
      major classes of glutamate receptors: ionotropic and metabotropic receptors.
      Ionotropic receptors contain three subtype receptors, including N-methyl-d
      aspartate (NMDA) receptors. Activation of NMDA receptors is important for
      initiating long-lasting changes in synapses. In the forebrain structures that are
      known to contribute to the formation and storage of information, NMDA receptors
      have an important role in persistent inflammatory pain by reinforcing glutamate
      sensory transmission. Mice with enhanced forebrain NMDA receptor function
      demonstrate selective enhancement of persistent pain and allodynia. Drugs
      targeting NMDA NR2B subunits in the forebrain could serve as a new class of
      medicine for controlling persistent pain in humans.

PMID- 11839526
TI  - Introduction: pre- and postnatal lung development, maturation, and plasticity.

PMID- 11839527
TI  - Invited Review: pulmonary alveoli: formation, the "call for oxygen," and other
      regulators.
AB  - The lung's only known essential function is to provide sufficient alveolar
      surface to meet the organism's need for oxygen and elimination of CO(2). The
      importance of the magnitude of alveolar surface area (Sa) to O(2) uptake (VO(2))
      is supported by the presence among mammals of a direct linear relationship
      between Sa and VO(2). This match has been achieved, despite the higher body mass
      specific VO(2) of small organisms compared with large, by a greater subdivision
      of alveolar surface, not by a larger relative lung volume in small organisms.
      This highly conserved relationship between alveolar architecture and VO(2)
      suggests the presence of similarly conserved mechanisms that control the onset,
      rate, and cessation of alveolus formation and alveolar size, which are also
      influenced by retinoids and thyroid and corticosteroid hormones. Furthermore, the
      "call for oxygen" is met at a breathing rate and tidal volume at which the work
      of breathing is lowest. Thus there is a complex, fascinating, but poorly
      understood, signaling relationship among VO(2), the neural regulation of
      breathing, and lung architecture, composition, and mechanics.

PMID- 11839528
TI  - Thyroid hormone affects embryonic mouse lung branching morphogenesis and cellular
      differentiation.
AB  - Although thyroid hormone (T(3)) influences epithelial cell differentiation during
      late fetal lung development, its effects on early lung morphogenesis are unknown.
      We hypothesized that T(3) would alter embryonic lung airway branching and
      temporal-spatial differentiation of the lung epithelium and mesenchyme.
      Gestational day 11.5 embryonic mouse lungs were cultured for 72 h in BGJb serum
      free medium without or with added T(3) (0.2, 2.0, 10.0, or 100 nM). Evaluation of
      terminal bud counts showed a dose- and time-dependent decrease in branching
      morphogenesis. Cell proliferation was also significantly decreased with higher
      doses of T(3). Morphometric analysis of lung histology showed that T(3) caused a
      dose-dependent decrease in mesenchyme and increase in cuboidal epithelia and
      airway space. Immunocytochemistry showed that with T(3) treatment, Nkx2.1 and
      surfactant protein SP-C proteins became progressively localized to cuboidal
      epithelial cells and mesenchymal expression of Hoxb5 was reduced, a pattern
      resembling late fetal lung development. We conclude that exogenous T(3) treatment
      during early lung development accelerated epithelial and mesenchymal cell
      differentiation at the expense of premature reduction in new branch formation and
      lung growth.

PMID- 11839529
TI  - MEK-1/2 inhibition reduces branching morphogenesis and causes mesenchymal cell
      apoptosis in fetal rat lungs.
AB  - The roles of the mitogen-activated protein (MAP) kinases extracellular signal
      regulated kinases-1 and -2 (ERK-1/2) in fetal lung development have not been
      extensively characterized. To determine if ERK-1/2 signaling plays a role in
      fetal lung branching morphogenesis, U-0126, an inhibitor of the upstream kinase
      MAP ERK kinase (MEK), was added to fetal lung explants in vitro. Morphometry as
      measured by branching, area, perimeter, and complexity were significantly reduced
      in U-0126-treated lungs. At the same time, U-0126 treatment reduced ERK-1/2,
      slightly increased p38 kinase, but did not change c-Jun NH(2)-terminal kinase
      activities, indicating that U-0126 specifically inhibited the ERK-1/2 enzymes.
      These changes were associated with increased apoptosis as measured by terminal
      deoxynucleotidyl transferase-mediated dUTP nick end labeling and
      immunofluorescent labeling of anti-active caspase-3 in the mesenchyme of explants
      after U-0126 treatment compared with the control. Mitosis characterized by
      immunolocalization of proliferating cell nuclear antigen was found predominantly
      in the epithelium and was reduced in U-0126-treated explants. Thus U-0126 causes
      specific inhibition of ERK-1/2 signaling, diminished branching morphogenesis,
      characterized by increased mesenchymal apoptosis, and decreased epithelial
      proliferation in fetal lung explants.

PMID- 11839530
TI  - Nitric oxide modulates branching morphogenesis in fetal rat lung explants.
AB  - Cells of the developing lung express the constitutive nitric oxide synthases
      (NOSs) I and III. The developmental importance of these enzymes is largely
      unknown, although a role for nitric oxide (NO) in the regulation of pulmonary
      blood flow at birth is established. Known effects of NO on transcription factors,
      apoptosis, and cellular proliferation, plus the time and spatial limits of
      pulmonary NOS expression, suggest that NO might influence lung development. We
      tested the potential of NO to modulate lung branching morphogenesis by exposing
      lung explants from gestational day 13 rat fetuses to varying doses of several NO
      donors (NONO-ate). We counted the number of airway branches that were added
      between the first and 72nd h of culture. NO released only from a NONO-ate with a
      long half-life [(Z)-1-[2-(2-aminoethyl)-N-(2-ammonioethyl)amino]-diazen-1-ium-1,2
      diolate-NO], increased branching in ambient O(2) by twofold. The NO effect was
      not mimicked with a cyclic guanine monophosphate analog; nonspecific NOS
      inhibitors in millimolar concentrations inhibited branching. We conclude that
      endogenous and exogenous NO can modulate branching morphogenesis in the rat lung.

PMID- 11839531
TI  - Antisense inhibition of surfactant protein A decreases tubular myelin formation
      in human fetal lung in vitro.
AB  - Surfactant protein A (SP-A) is the most abundant of the surfactant-associated
      proteins. SP-A is involved in the formation of tubular myelin, the modulation of
      the surface tension-reducing properties of surfactant phospholipids, the
      metabolism of surfactant phospholipids, and local pulmonary host defense. We
      hypothesized that elimination of SP-A would alter the regulation of SP-B gene
      expression and the formation of tubular myelin. Midtrimester human fetal lung
      explants were cultured for 3-5 days in the presence or absence of an antisense 18
      mer phosphorothioate oligonucleotide (ON) complementary to SP-A mRNA. After 3
      days in culture, SP-A mRNA was undetectable in antisense ON-treated explants.
      After 5 days in culture, levels of SP-A protein were also decreased by antisense
      treatment. SP-B mRNA levels were not affected by the antisense SP-A ON treatment.
      However, there was decreased tubular myelin formation in the antisense SP-A ON
      treated tissue. We conclude that selective elimination of SP-A mRNA and protein
      results in a decrease in tubular myelin formation in human fetal lung without
      affecting SP-B mRNA. We speculate that SP-A is critical to the formation of
      tubular myelin during human lung development and that the regulation of SP-B gene
      expression is independent of SP-A gene expression.

PMID- 11839532
TI  - Human surfactant protein B promoter in transgenic mice: temporal, spatial, and
      stimulus-responsive regulation.
AB  - Surfactant protein B (SP-B) is a developmentally and hormonally regulated lung
      protein that is required for normal surfactant function. We generated transgenic
      mice carrying the human SP-B promoter (-1,039/+431 bp) linked to chloramphenicol
      acetyltransferase (CAT). CAT activity was high in lung and immunoreactive protein
      localized to alveolar type II and bronchiolar epithelial cells. In addition,
      thyroid, trachea, and intestine demonstrated CAT activity, and each of these
      tissues also expressed low levels of SP-B mRNA. Developmental expression of CAT
      activity and SP-B mRNA in fetal lung were similar and both increased during
      explant culture. SP-B mRNA but not CAT activity decreased during culture of adult
      lung, and both were reduced by transforming growth factor (TGF)-beta(1).
      Treatment of adult mice with intratracheal bleomycin caused similar time
      dependent decreases in lung SP-B mRNA and CAT activity. These findings indicate
      that the human SP-B promoter fragment directs tissue- and lung cell-specific
      transgene expression and contains cis-acting elements involved in regulated
      expression during development, fetal lung explant culture, and responsiveness to
      TGF-beta and bleomycin-induced lung injury.

PMID- 11839533
TI  - Leptin mediates the parathyroid hormone-related protein paracrine stimulation of
      fetal lung maturation.
AB  - Developing rat lung lipofibroblasts express leptin beginning on embryonic day (E)
      17, increasing 7- to 10-fold by E20. Leptin and its receptor are expressed
      mutually exclusively by fetal lung fibroblasts and type II cells, suggesting a
      paracrine signaling "loop." This hypothesized mechanism is supported by the
      following experimental data: 1) leptin stimulates the de novo synthesis of
      surfactant phospholipid by both fetal rat type II cells (400% x 100 ng(-1) x ml(
      1) x 24 h(-1)) and adult human airway epithelial cells (85% x 100 ng(-1) x 24 h(
      1)); 2) leptin is secreted by lipofibroblasts in amounts that stimulate type II
      cell surfactant phospholipid synthesis in vitro; 3) epithelial cell secretions
      such as parathyroid hormone-related protein (PTHrP), PGE(2), and dexamethasone
      stimulate leptin expression by fetal rat lung fibroblasts; 4) PTHrP or leptin
      stimulate the de novo synthesis of surfactant phospholipid (2- to 2.5-fold/24 h)
      and the expression of surfactant protein B (SP-B; >25-fold/24 h) by fetal rat
      lung explants, an effect that is blocked by a leptin antibody; and 5) a PTHrP
      receptor antagonist inhibits the expression of leptin mRNA by explants but does
      not inhibit leptin stimulation of surfactant phospholipid or SP-B expression,
      indicating that PTHrP paracrine stimulation of type II cell maturation requires
      leptin expression by lipofibroblasts. This is the first demonstration of a
      paracrine loop that functionally cooperates to induce alveolar acinar lung
      development.

PMID- 11839534
TI  - Intra-amniotic injection of IL-1 induces inflammation and maturation in fetal
      sheep lung.
AB  - Antenatal inflammation may be an important triggering event in the pathogenesis
      of bronchopulmonary dysplasia but may also accelerate fetal lung maturation. We
      examined the effects of intra-amniotic (IA) interleukin (IL)-1 alpha and IL-1
      beta on maturation of the fetal sheep lung. These cytokine effects were compared
      with IA endotoxin, a potent proinflammatory stimulus that accelerated lung
      maturation. Date-bred ewes received 15 or 150 microg recombinant ovine IL-1 alpha
      or IL-1 beta or 10 mg Escherichia coli endotoxin by IA injection at 118 days
      gestation (term = 150 days), and fetuses were delivered at 125 days. IL-1 alpha
      and IL-1 beta improved lung function and increased alveolar saturated
      phosphatidylcholine (Sat PC) and surfactant protein mRNA expression at the higher
      dose. The maturation response to IL-1 alpha was greater than that to IL-1 beta,
      which was similar to endotoxin response. Inflammation was also more pronounced
      after IL-1 alpha treatment. Only endotoxin animals had residual inflammation of
      the fetal membranes at 7 days. Lung compliance, lung volume, and alveolar Sat PC
      were positively correlated with residual alveolar wash leukocyte numbers 7 days
      after IL-1 treatment, suggesting a link between lung inflammation and maturation.

PMID- 11839535
TI  - Axonemal dynein expression in human fetal tracheal epithelium.
AB  - Ciliogenesis in human fetal airway epithelium occurs from 11 to 24 gestational
      weeks. Using genetic and antigenic markers specific for human axonemal dynein
      heavy chain 9, we characterized temporal aspects of axonemal dynein expression
      associated with large airway epithelial ciliogenesis during human fetal
      development. Late in the first trimester, an undifferentiated columnar epithelium
      is characteristic of the large airways, and immunocytochemical studies exhibited
      focal localization of axonemal dynein antigen on luminal epithelial cell borders
      at sites consistent with emergent ciliary beds. From 12 to 22 wk,
      immunocytochemical labeling of new ciliary beds was prominent, and localization
      within the cytoplasm of epithelial cells suggested avid synthesis of axonemal
      dynein in advance of ciliogenic events. Quantitative RT-PCR of tracheal RNA and
      in situ hybridization studies compared favorably with immunocytochemical findings
      with the earliest expression of axonemal dynein at 9-10 wk gestation. These
      studies have documented that axonemal dynein is expressed early in human fetal
      life during airway epithelial maturation and well before histological or
      ultrastructural evidence of ciliogenesis is apparent.

PMID- 11839536
TI  - Effects of oligohydramnios on lung growth and maturation in the fetal rat.
AB  - Oligohydramnios (OH) retards fetal lung growth by producing less lung distension
      than normal. To examine effects of decreased distension on fetal lung
      development, we produced OH in rats by puncture of uterus and fetal membranes at
      16 days of gestation; fetuses were delivered at 21 or 22 days of gestation.
      Controls were position-matched littermates in the opposite uterine horn. OH lungs
      had lower weights and less DNA, protein, and water, but no differences in
      saturated phosphatidylcholine, surfactant proteins (SP)-A and -B, and mRNA for SP
      A, -B, -C, and -D. To evaluate effects on epithelial differentiation, we used
      RTI(40) and RTII(70), proteins specific in lung to luminal surfaces of alveolar
      type I and II cells, respectively. At 22 days of gestation, OH lungs had less
      RTI(40) mRNA (P < 0.05) and protein (P < 0.001), but RTII(70) did not differ from
      controls. With OH, type I cells (in proportion to type II cells) covered less
      distal air space perimeter (P < 0.01). We conclude that OH, which retards lung
      growth, has little effect on surfactant and impedes formation of type I cells
      relative to type II cells.

PMID- 11839537
TI  - Increased expansion of the lung stimulates calmodulin 2 expression in fetal
      sheep.
AB  - Obstruction of the fetal trachea causes the lungs to expand with accumulated
      liquid. Although this is a potent stimulus for lung growth, the mechanisms
      involved are unknown. Our aim was to identify genes that are differentially
      expressed as a result of increased fetal lung expansion. Using differential
      display RT-PCR, we isolated a cDNA fragment partially encoding calmodulin 2
      (CALM2) and identified the remainder of the coding region by 5'-rapid
      amplification of cDNA ends. Differential expression of CALM2 was confirmed by
      Northern blot analysis; CALM2 mRNA levels were increased to 161 +/- 5% of control
      at 2 days of increased lung expansion, induced by tracheal obstruction (TO), and
      had returned to control levels at days 4 and 10. Using in situ hybridization
      analysis, we found that the proportion of CALM2-labeled cells increased from 10.3
      +/- 1.0% to 21.4 +/- 6.8% by 2 days of TO. This increase in CALM2 expression was
      reflected by a tendency for calmodulin protein levels to increase from 122.7 +/-
      17.3 to 156.5 +/- 17.7 at 2 days of TO. Thus increases in fetal lung expansion
      result in time-dependent changes in CALM2 mRNA levels, which closely parallels
      the changes in lung DNA synthesis rates. As calmodulin is essential for cell
      proliferation, increased CALM2 mRNA levels may reflect an important role for
      calmodulin in expansion-induced fetal lung growth.

PMID- 11839538
TI  - Cyclic mechanical stretch inhibits cell proliferation and induces apoptosis in
      fetal rat lung fibroblasts.
AB  - Development of the pulmonary air sacs is crucial for extrauterine survival. Late
      fetal lung development is characterized by a thinning of the mesenchyme, which
      brings pneumocytes and endothelial cells into apposition. We hypothesized that
      mechanical stretch, simulating fetal breathing movements, plays an important role
      in this remodeling process. Using a Flexercell Strain Unit, we analyzed the
      effects of intermittent stretch on cell proliferation and apoptosis activation in
      fibroblasts isolated from fetal rat lungs during late development. On day 19,
      intermittent stretch increased cells in G(0)/G(1) by 22% (P = 0.001) and
      decreased in S phase by 50% (P = 0.003) compared with unstretched controls. Cell
      proliferation analyzed by 5-bromo-2'-deoxyuridine incorporation showed a similar
      magnitude of cell cycle arrest (P = 0.04). At this same gestational age, stretch
      induced apoptosis by two- to threefold over controls, assayed by DNA flow
      cytometry, terminal deoxynucleotidyl transferase-mediated dUTP-FITC nick-end
      labeling, and caspase-3 activation. These results indicate that mechanical
      stretch of fibroblasts isolated during the canalicular stage inhibits cell cycle
      progression and activates apoptosis. These findings are cotemporal with the
      mesenchymal thinning that normally occurs in situ.

PMID- 11839539
TI  - Insulin-like growth factor I receptor is downregulated after alveolarization in
      an apoptotic fibroblast subset.
AB  - After alveolar formation, >20% of interstitial lung fibroblasts undergo
      apoptosis, a process that is of critical importance for normal lung maturation.
      The immature lung contains two morphologically distinct fibroblast populations,
      lipid-filled interstitial fibroblasts (LIF) and non-LIF (NLIF), which differ with
      respect to contractile protein content, proliferative capacity, and expression of
      mRNAs for fibronectin and types I and III collagen, but not tropoelastin. After
      alveolarization, apoptosis occurs in only one fibroblast population, the LIF.
      Using flow cytometry to analyze fibroblasts stained with a lipophilic,
      fluorescent dye, we identified a subset, designated LIF(-), that contained fewer
      lipid droplets. Unlike LIF that retain lipid, LIF(+), the LIF(-) do not undergo
      apoptosis after alveolarization. In LIF(+), apoptosis was correlated with
      downregulation of insulin-like growth factor I receptor (IGF-IR) mRNA and cell
      surface protein expression. Treatment with anti-IGF-IR decreased total lung
      fibroblast survival (P = 0.05) as did treatment with the phosphatidylinositol 3
      kinase inhibitor LY-294002 and the ras-raf-mitogen-activated protein kinase
      inhibitor PD-98059 (P < 0.002), which block IGF-I/insulin receptor survival
      pathways. These observations implicate downregulation of IGF-IR expression in
      fibroblast apoptosis after alveolar formation.

PMID- 11839540
TI  - Temporal/spatial expression of retinoid binding proteins and RAR isoforms in the
      postnatal lung.
AB  - Endogenous retinoids have been implicated in alveologenesis in both the rat and
      the mouse, and exogenous retinoic acid (RA) can reverse or partially reverse
      experimental emphysema in adult rat and mouse models by an unknown mechanism. In
      this study, we examine the cellular and molecular biology of retinoid signaling
      during alveologenesis in the mouse. We describe the temporal and spatial
      expression of the retinoid binding proteins CRBP-I, CRBP-II, and CRABP-I using RT
      PCR and immunohistochemistry. We identify the retinoic acid receptor isoforms RAR
      alpha 1, RAR-beta 2, RAR-beta 4, and RAR-gamma 2 and describe their temporal and
      spatial expression using RT-PCR and in situ hybridization. We demonstrate that
      both retinoid binding proteins and RAR isoforms are temporally regulated and
      found within the alveolar septal regions during alveologenesis. These data
      support a role of dynamic endogenous RA signaling during alveolar formation.

PMID- 11839541
TI  - Suppression of cell proliferation and programmed cell death by dexamethasone
      during postnatal lung development.
AB  - Prematurely born babies are often treated with glucocorticoids. We studied the
      consequences of an early postnatal and short dexamethasone treatment (0.1-0.01
      microg/g, days 1-4) on lung development in rats, focusing on its influence on
      peaks of cell proliferation around day 4 and of programmed cell death at days 19
      21. By morphological criteria, we observed a dexamethasone-induced premature
      maturation of the septa (day 4), followed by a transient septal immatureness and
      delayed alveolarization leading to complete rescue of the structural changes. The
      numbers of proliferating (anti-Ki67) and dying cells (TdT-mediated dUTP nick end
      labeling) were determined and compared with controls. In dexamethasone-treated
      animals, both the peak of cell proliferation and the peak of programmed cell
      death were reduced to baseline, whereas the expression of tissue transglutaminase
      (transglutaminase-C), another marker for postnatal lung maturation, was not
      significantly altered. We hypothesize that a short neonatal course of
      dexamethasone leads to severe but transient structural changes of the lung
      parenchyma and influences the balance between cell proliferation and cell death
      even in later stages of lung maturation.

PMID- 11839542
TI  - Detection of chondroitin sulfates and decorin in developing fetal and neonatal
      rat lung.
AB  - Chondroitin sulfates and their related proteoglycans are components of
      extracellular matrix that act as key determinants of growth and differentiation
      characteristics of developing lungs. Changes in their immunohistochemical
      distribution during progressive organ maturation were examined with monospecific
      antibodies to chondroitin sulfate, a nonbasement membrane chondroitin sulfate
      proteoglycan, and the specific chondroitin sulfate-containing proteoglycan
      decorin in whole fetuses and lungs from newborn and adult rats. Alveolar and
      airway extracellular matrix immunostained heavily in the prenatal rat for both
      chondroitin sulfate and chondroitin sulfate proteoglycan, whereas decorin was
      confined to developing airways and vessels. These sites retained their respective
      levels of reactivity with all antibodies through 1-10 days postnatal but
      thereafter became progressively more diminished and focal in alveolar regions.
      The heavy staining seen early in development was interpreted to reflect a
      significant and wide distribution of chondroitin sulfates, chondroitin sulfate
      proteoglycans, and decorin in rapidly growing tissues, whereas the reduced and
      more focal reactivity observed at later time points coincided with known focal
      patterns of localization of fibrillar elements of the extracellular matrix and a
      more differentiated state.

PMID- 11839543
TI  - LPS-induced lung injury in neonatal rats: changes in gelatinase activities and
      consequences on lung growth.
AB  - Postnatal lung growth disorders may involve imbalance between metalloproteinases
      and their inhibitors. Inflammatory cell 92-kDa gelatinase overactivity has been
      reported in adults with lung injury but has not been looked for in neonates. We
      compared gelatinase activity in neonatal and adult rats and evaluated postnatal
      lung growth after lipopolysaccharide (LPS)-induced lung injury. Significant intra
      alveolar inflammatory cell recruitment occurred in adults and neonates; cell
      counts increased 16-fold in adults and 2.7-fold in neonates. Total 92-kDa
      gelatinase activity was increased in neonates and adults and was significantly
      correlated to inflammatory cell counts. For a given cell count, 92-kDa gelatinase
      increased more in neonates than in adults. Morphometric neonatal lung analysis
      showed that LPS-injured lungs had decreases in absolute values of lung volume (P
      < 0.03), alveolar surface (P < 0.004), and air space volume (P < 0.03).
      Doxycycline, a nonspecific metalloproteinase inhibitor, partly inhibited LPS
      induced 92-kDa gelatinase overactivity but did not improve LPS-induced alveolar
      growth disorders. LPS-mediated lung injury in neonatal rats induced both
      gelatinase B overactivity and alveolar growth disorders, although no causal link
      between these two effects was demonstrated.

PMID- 11839544
TI  - ClC-5: ontogeny of an alternative chloride channel in respiratory epithelia.
AB  - Chloride transport is critical to many functions of the lung. Molecular defects
      in the best-known chloride channel, cystic fibrosis transmembrane conductance
      regulator (CFTR), lead to impaired function of airway defensins, hydration of
      airway surface fluid, and mucociliary clearance leading to chronic lung disease,
      and premature death, but do not cause defects in lung development. We examined
      the expression of one member of the ClC family of volume- and voltage-regulated
      channels using the ribonuclease protection assay and Western blot analysis in
      rats. ClC-5 mRNA and protein are most strongly expressed in the fetal lung, and
      expression is maintained although downregulated postnatally. In addition, using
      immunocytochemistry, we find that ClC-5 is predominantly expressed along the
      luminal surface of the airway epithelium, suggesting that ClC-5 may participate
      in lung chloride secretion. Identifying candidate genes for critical ion
      transport functions is essential for understanding normal lung morphogenesis and
      the pathophysiology of several lung diseases. In addition, the manipulation of
      non-CFTR chloride channels may provide a viable approach for treating cystic
      fibrosis lung disease.

PMID- 11839545
TI  - Distal air space epithelial fluid clearance in near-term rat fetuses is fast and
      requires endogenous catecholamines.
AB  - Knowledge about the conversion of the epithelium in the distal air spaces of the
      lung from secretion to absorption is imperative to the understanding of postnatal
      lung development; little such information is available in rats. Distal air space
      fluid clearance was therefore measured in 21- to 22-day gestation rat fetuses and
      newborn (40 h) rats. Distal air space fluid clearance was measured from the
      increase in (131)I-albumin concentration in an isosmolar, physiological solution
      instilled into the developing lungs. There was no net fluid movement across the
      distal air space epithelium in the lungs of 21-day gestation fetuses. Twenty-four
      hours later, distal air space fluid was cleared at a rapid rate in the 22-day
      gestation fetuses. Within the first 40 h after birth, the rate rapidly declined
      to adult levels. The high distal air space fluid clearance at 22 days gestation
      and at 40 h after birth was mediated by beta-adrenergic receptors as demonstrated
      by elevated plasma epinephrine levels and inhibition by propranolol.
      Interestingly, the elevated distal air space fluid clearance in the 22-day
      gestation fetuses was only minimally amiloride sensitive; however, amiloride
      sensitivity increased over the first 40 h after birth. In conclusion, these
      studies demonstrate that 1) rapid rates of net alveolar fluid clearance occur
      late in gestation in the rat and 2) this clearance is driven by elevations of
      endogenous epinephrine.

PMID- 11839546
TI  - Pulmonary surfactant protein D: a novel link between innate and adaptive
      immunity.

PMID- 11839547
TI  - Airway smooth muscle: new tricks for an old dog.

PMID- 11839548
TI  - IL-13-dependent autocrine signaling mediates altered responsiveness of IgE
      sensitized airway smooth muscle.
AB  - In testing the hypothesis that interleukin-4 receptor alpha-subunit (IL-4R alpha)
      coupled signaling mediates altered airway smooth muscle (ASM) responsiveness in
      the atopic sensitized state, isolated rabbit tracheal ASM segments were passively
      sensitized with immunoglobulin E (IgE) immune complexes, both in the absence and
      presence of an IL-4R alpha blocking antibody (anti-IL-4R alpha Ab). Relative to
      control ASM, IgE-sensitized tissues exhibited enhanced isometric constrictor
      responses to administered ACh and attenuated relaxation responses to
      isoproterenol. These proasthmatic-like effects were prevented in IgE-sensitized
      ASM that were pretreated with anti-IL-4R alpha Ab. In complementary experiments,
      IgE-sensitized cultured human ASM cells exhibited upregulated expression of IL-13
      mRNA and protein, whereas IL-4 expression was undetected. Moreover, extended
      studies demonstrated that 1) exogenous IL-13 administration to naive ASM elicited
      augmented contractility to ACh and impaired relaxation to isoproterenol, 2) these
      effects of IL-13 were prevented by pretreating the tissues with an IL-5 receptor
      blocking antibody, and 3) IL-13 administration induced upregulated mRNA
      expression and release of IL-5 protein from cultured ASM cells. Collectively,
      these findings provide new evidence demonstrating that the altered responsiveness
      of IgE-sensitized ASM is largely attributed to activation of an intrinsic Th2
      type autocrine mechanism involving IL-13/IL-4R alpha-coupled release and action
      of IL-5 in the sensitized ASM itself.

PMID- 11839549
TI  - Platelets inhibit the lysis of pulmonary microemboli.
AB  - Using tracings of (125)I-labeled fibrin(ogen) in rodents, we examined the
      hypothesis that platelets impede the lysis of pulmonary emboli. (125)I
      Microemboli (ME, 3-10 micron diameter) lodged homogeneously throughout the lungs
      after intravenous injection in both rats and mice (60% of injected dose), caused
      no lethality, and underwent spontaneous dissolution (50 and 100% within 1 and 5
      h, respectively). Although lung homogenates displayed the most intense
      fibrinolytic activity of all the major organs, dissolution of ME was much slower
      in isolated perfused lungs (IPL) than was observed in vivo. Addition of rat
      plasma to the perfusate facilitated ME dissolution in IPL to a greater extent
      than did addition of tissue-type plasminogen activator alone, suggesting that
      permeation of the clot by plasminogen is the rate-limited step in lysis. Platelet
      containing ME injected in rats lysed much more slowly than did ME formed from
      fibrin alone. (125)I-Thrombi, formed in the pulmonary vasculature of mice in
      response to intravascular activation of platelets by injection of collagen and
      epinephrine, were essentially resistant to spontaneous dissolution. Moreover,
      injection of the antiplatelet glycoprotein IIb/IIIa antibody 7E3 F(ab')(2)
      facilitated spontaneous dissolution of pulmonary ME and augmented fibrinolysis by
      a marginally effective dose of Retavase (10 microg/kg) in rats. These studies
      show that platelets suppress pulmonary fibrinolysis. The mechanism(s) by which
      platelets stabilize ME and utility of platelet inhibitors to facilitate their
      dissolution deserves further study.

PMID- 11839550
TI  - Susceptibility to ozone-induced acute lung injury in iNOS-deficient mice.
AB  - Mice deficient in inducible nitric oxide synthase (iNOS; C57Bl/6Ai-[KO]NOS2 N5)
      or wild-type C57Bl/6 mice were exposed to 1 part/million of ozone 8 h/night or to
      filtered air for three consecutive nights. Endpoints measured included lavagable
      total protein, macrophage inflammatory protein (MIP)-2, matrix metalloproteinase
      (MMP)-9, cell content, and tyrosine nitration of whole lung proteins. Ozone
      exposure caused acute edema and an inflammatory response in the lungs of wild
      type mice, as indicated by significant increases in lavage protein content, MIP-2
      and MMP-9 content, and polymorphonuclear leukocytes. The iNOS knockout mice
      showed significantly greater levels of lung injury by all of these criteria than
      did the wild-type mice. We conclude that iNOS knockout mice are more susceptible
      to acute lung damage induced by exposure to ozone than are wild-type C57Bl/6 mice
      and that protein nitration is associated with the degree of inflammation and not
      dependent on iNOS-derived nitric oxide.

PMID- 11839551
TI  - M. tuberculosis induction of matrix metalloproteinase-9: the role of mannose and
      receptor-mediated mechanisms.
AB  - Mycobacterium tuberculosis (Mtb) infection induces the expression of matrix
      metalloproteinase-9 (MMP-9) in mouse lungs. In cultured human monocytic cells,
      Mtb bacilli and the cell wall glycolipid lipoarabinomannan (LAM) stimulate high
      levels of MMP-9 activity. Here, we explore the cellular mechanisms involved in
      the induction of MMP-9 by Mtb. We show that infection of THP-1 cells with Mtb
      caused a fivefold increase in MMP-9 mRNA that was associated with increased MMP-9
      activity. MMP-9 induction was dependent on microtubule polymerization and protein
      kinase activation and was associated with increased DNA binding by the
      transcription factor activator protein-1 (AP-1), which appeared to be important
      for MMP-9 expression. We then explored the surface molecules potentially involved
      in Mtb induction of MMP-9, focusing on ligands of the mannose and beta-glucan
      receptors. MMP-9 activity was induced by the mannose receptor ligands mannan,
      zymosan, and LAM, whereas the beta-glucan receptor ligand laminarin was not
      effective. The most active inducers of MMP-9 activity were the particulate ligand
      zymosan and LAM. Pretreatment of cells with an anti-mannose receptor monoclonal
      antibody, but not anti-complement receptor 3, decreased the induction of MMP-9
      activity by Mtb bacilli. Together, these results suggest that MMP-9 induction by
      Mtb occurs by receptor-mediated signaling mechanisms involving the binding of
      mannosylated ligands to mannose receptors, the modulation by cytoskeletal
      elements such as microtubules, the activation of protein kinases, and
      transcriptional activation by AP-1.

PMID- 11839552
TI  - Adenosine A(3) receptor-mediated potentiation of mucociliary transport and
      epithelial ciliary motility.
AB  - To examine the effect of adenosine A(3) receptor stimulation on airway
      mucociliary clearance, we measured transport of Evans blue dye in rabbit trachea
      in vivo and ciliary motility of epithelium by the photoelectric method in vitro.
      Mucociliary transport was enhanced dose dependently by the selective A(3) agonist
      N(6)-(3-iodobenzyl)-5'-N-methylcarbamoyladenosine (IB-MECA) and to a lesser
      extent by the less-selective N(6)-2-(4-amino-3-iodophenyl)ethyladenosine, whereas
      the A(1) agonist N-cyclopentyladenosine (CPA) and the A(2) agonist CGS-21680 had
      no effect. The effect of IB-MECA was abolished by pretreatment with the selective
      A(3) antagonist MRS-1220 but not by the A(1) antagonist 1,3-dipropyly-8
      cyclopentylxanthine or the A(2) antagonist 3,7-dimethyl-L-propargylxanthine.
      Epithelial ciliary beat frequency was increased by IB-MECA in a concentration
      dependent manner, the maximal increase being 33%, and this effect was inhibited
      by MRS-1220. The IB-MECA-induced ciliary stimulation was not altered by the Rp
      diastereomer of cAMP but was greatly inhibited by Ca(2+)-free medium containing
      BAPTA-AM. Incubation with IB-MECA increased intracellular Ca(2+) contents.
      Therefore, A(3) agonist enhances airway mucociliary clearance probably through
      Ca(2+)-mediated stimulation of ciliary motility of airway epithelium.

PMID- 11839553
TI  - Absence of SP-A modulates innate and adaptive defense responses to pulmonary
      influenza infection.
AB  - Mice lacking surfactant protein SP-A [SP-A(-/-)] and wild type SP-A(+/+) mice
      were infected with influenza A virus (IAV) by intranasal instillation. Decreased
      clearance of IAV was observed in SP-A(-/-) mice and was associated with increased
      pulmonary inflammation. Treatment of SP-A(-/-) mice with exogenous SP-A enhanced
      viral clearance and decreased lung inflammation. Uptake of IAV by alveolar
      macrophages was similar in SP-A(-/-) and SP-A(+/+) mice. Myeloperoxidase activity
      was reduced in isolated bronchoalveolar lavage neutrophils from SP-A(-/-) mice. B
      lymphocytes and activated T lymphocytes were increased in the lung and spleen,
      whereas T helper (Th) 1 responses were increased [interferon-gamma, interleukin
      (IL)-2, and IgG(2a)] and Th2 responses were decreased (IL-4, and IL-10, and
      IgG(1)) in the lungs of SP-A(-/-) mice 7 days after IAV infection. In the absence
      of SP-A, impaired viral clearance was associated with increased lung
      inflammation, decreased neutrophil myeloperoxidase activity, and increased Th1
      responses. Because the airway is the usual portal of entry for IAV and other
      respiratory pathogens, SP-A is likely to play a role in innate defense and
      adaptive immune responses to IAV.

PMID- 11839554
TI  - Alterations in lung collectins in an adaptive allergic immune response.
AB  - Although surfactant apoproteins are known to be mediators of innate responses,
      their relationship to adaptive responses has not been examined extensively. We
      investigated possible links between surfactant apoproteins and responses to
      allergens by studying alterations in surfactant apoproteins A, B, and D in a
      murine model of allergic pulmonary inflammation. Three murine strains (BALB/c,
      C57BL/6, and 129J) demonstrated increased immunostaining of surfactant
      apoproteins A and D in nonciliated epithelial cells of noncartilaginous airways
      after aerosolized challenge. In contrast, surfactant apoprotein B immunostaining
      was unchanged. Immunoblotting demonstrated increased surfactant A in
      bronchoalveolar lavage fluid after allergen sensitization and challenge.
      Surfactant apoprotein A and D induction required T and/or B lymphocyte responses
      to allergen, since the induction was absent in recombinase-activating gene
      deficient mice, which lack functional lymphocytes. We conclude that increased
      immunoreactivity of two collectins, surfactant apoproteins A and D, occurs within
      the response to allergen. Our findings support a model in which surfactant
      apoproteins A and D are important to both innate immunity and adaptive immune
      responses to allergens.

PMID- 11839555
TI  - Smad3 deficiency attenuates bleomycin-induced pulmonary fibrosis in mice.
AB  - Transforming growth factor-beta (TGF-beta) signaling plays an important
      regulatory role during lung fibrogenesis. Smad3 was identified in the pathway for
      transducing TGF-beta signals from the cell membrane to the nucleus. Using mice
      without Smad3 gene expression, we investigated whether Smad3 could regulate
      bleomycin-induced pulmonary fibrosis in vivo. Mice deficient in Smad3
      demonstrated suppressed type I procollagen mRNA expression and reduced
      hydroxyproline content in the lungs compared with wild-type mice treated with
      bleomycin. Furthermore, loss of Smad3 greatly attenuated morphological fibrotic
      responses to bleomycin in the mouse lungs, suggesting that Smad3 is implicated in
      the pathogenesis of pulmonary fibrosis. These results show that Smad3 contributes
      to bleomycin-induced lung injury and that Smad3 may serve as a novel target for
      potential therapeutic treatment of lung fibrosis.

PMID- 11839558
TI  - Oxidative damage and cancer.

PMID- 11839559
TI  - Neuropathological verisimilitude in animal models of Alzheimer's disease: key to
      elucidating neurodegenerative pathways and identifying new targets for drug
      discovery.

PMID- 11839557
TI  - Beta-catenin--a linchpin in colorectal carcinogenesis?
AB  - An important role for beta-catenin pathways in colorectal carcinogenesis was
      first suggested by the protein's association with adenomatous polyposis coli
      (APC) protein, and by evidence of dysregulation of beta-catenin protein
      expression at all stages of the adenoma-carcinoma sequence. Recent studies have,
      however, shown that yet more components of colorectal carcinogenesis are linked
      to beta-catenin pathways. Pro-oncogenic factors that also release beta-catenin
      from the adherens complex and/or encourage translocation to the nucleus include
      ras, epidermal growth factor (EGF), c-erbB-2, PKC-betaII, MUC1, and PPAR-gamma,
      whereas anti-oncogenic factors that also inhibit nuclear beta-catenin signaling
      include transforming growth factor (TGF)-beta, retinoic acid, and vitamin D.
      Association of nuclear beta-catenin with the T cell factor (TCF)/lymphoid
      enhancer factor (LEF) family of transcription factors promotes the expression of
      several compounds that have important roles in the development and progression of
      colorectal carcinoma, namely: c-myc, cyclin D1, gastrin, cyclooxygenase (COX)-2,
      matrix metalloproteinase (MMP)-7, urokinase-type plasminogen activator receptor
      (aPAR), CD44 proteins, and P-glycoprotein. Finally, genetic aberrations of
      several components of the beta-catenin pathways, eg, Frizzled (Frz), AXIN, and
      TCF-4, may potentially contribute to colorectal carcinogenesis. In discussing the
      above interactions, this review demonstrates that beta-catenin represents a key
      molecule in the development of colorectal carcinoma.

PMID- 11839560
TI  - Nicotine and cotinine up-regulate vascular endothelial growth factor expression
      in endothelial cells.
AB  - Cigarette smoking is an important risk factor for both vascular disease and
      various forms of cancer. Vascular endothelial growth factor (VEGF) is an
      endothelial-specific mitogen that is normally expressed only in low levels in
      normal arteries but may be involved in the progression of both vascular disease
      and cancer. Some clinical evidence suggests that cigarette smoking may increase
      plasma VEGF levels, but there is a lack of basic science studies investigating
      this possibility. We show here, using an intact porcine common carotid artery
      perfusion culture model, that nicotine and cotinine, the major product of
      nicotine metabolism, cause a significant increase in endothelial cell VEGF
      expression. VEGF mRNA levels were compared between groups using reverse
      transcriptase-polymerase chain reaction, whereas protein level changes were
      demonstrated with Western blotting and immunohistochemistry. Our results showed
      significant increases in endothelial cell VEGF mRNA and protein levels because of
      nicotine and cotinine at concentrations representative of plasma concentrations
      seen in habitual smokers. VEGF immunostaining also paralleled these results.
      These findings may give a clue as to the mechanisms by which nicotine and
      cotinine from cigarette smoking increase vascular disease progression and tumor
      growth and metastasis.

PMID- 11839561
TI  - Specific allelic loss of p16 (INK4A) tumor suppressor gene after weeks of iron
      mediated oxidative damage during rat renal carcinogenesis.
AB  - Oxidative tissue damage has been shown to be associated with carcinogenesis. In
      human cancers p16(INK4A) is one of the most frequently mutated tumor suppressor
      genes. The present study used the ferric nitrilotriacetate (Fe-NTA)-induced rat
      renal carcinogenesis model to determine whether oxidative damage can cause
      specific allelic loss of p16 (INK4A). By the use of fluorescent in situ
      hybridization in combination with imprint cytology at single-cell resolution, we
      found that the number of renal tubular cells with aneuploidy (1 or 3 signals) at
      the p16(INK4A) locus was significantly and specifically increased (1 week, 37.2
      +/- 2.3%; 3 weeks, 37.8 +/- 1.3% vs control, 22.5 +/- 1.9%; mean +/- SE, N = 8; P
      < 0.001 and P < 0.0001, respectively) after repeated intraperitoneal
      administration of 5 to10 mg of iron/kg in the form of Fe-NTA for 3 weeks. No
      increase in aneuploidy was observed at the loci of either the p53 or vhl tumor
      suppressor gene. Furthermore, the increase in the cells with 3 signals was
      followed by a continuous increase in those with 1 signal. Therefore, the p16
      (INK4A) locus is specifically vulnerable to oxidative damage, leading to its
      allelic loss within weeks, presumably due to a deficiency in the replication of
      both the alleles.

PMID- 11839562
TI  - The co-expression of activating and inhibitory leukocyte immunoglobulin-like
      receptors in rheumatoid synovium.
AB  - Rheumatoid arthritis (RA) is a chronic inflammatory synovitis, with destruction
      of juxtaarticular cartilage and bone, likely mediated by lipid mediators,
      cytokines, and proteases released from inflammatory leukocytes. The mechanisms
      regulating leukocyte activation in rheumatoid synovium are not fully elucidated.
      A new family of cell surface proteins termed leukocyte immunoglobulin-like
      receptors (LIRs) has been shown in vitro to modulate cellular responses through
      immunoreceptor tyrosine-based inhibitory motifs or through association with the
      Fc receptor gamma chain that contains immunoreceptor tyrosine-based activation
      motifs. We studied the expression of inhibitory and activating LIRs in the
      synovium of six RA patients, three osteoarthritis patients, and three controls by
      immunohistochemistry. The synovium from patients with early RA showed extensive
      expression of the inhibitory LIR-2 and the activating LIR-7 on macrophages and
      neutrophils. Some mast cells and endothelial cells expressed LIR-7. There was
      limited expression of LIRs in synovium from two patients with long-standing RA,
      patients with osteoarthritis, and controls. LIR-2 recognizes MHC class I
      molecules. We therefore suggest that LIRs may regulate the activation of
      infiltrating leukocytes in synovial tissue and are a potential therapeutic
      target.

PMID- 11839563
TI  - Translocation, deletion/amplification, and expression of HMGIC and MDM2 in a
      carcinoma ex pleomorphic adenoma.
AB  - Carcinoma ex pleomorphic adenoma (CexPA) is a carcinoma developing within a pre
      existing benign pleomorphic adenoma (PA). Here we describe the identification and
      characterization of a series of genetic events leading to translocation,
      deletion/amplification, and overexpression of the HMGIC and MDM2 genes in a CexPA
      at an early stage of development. The tumor had a pseudodiploid stemline
      karyotype with a del(5)(q22-23q32-33) and a t(10;12)(p15;q14-15). In addition,
      there were several sidelines with double minute chromosomes (dmin) or
      homogeneously staining regions (hsr). Fluorescence in situ hybridization (FISH)
      mapping revealed that the 12q14-15 breakpoint was located centromeric to HMGIC
      and that the entire gene was juxtaposed to the der(10) chromosome. Detailed
      analysis of cells with dmin and hsr revealed that HMGIC and MDM2 were deleted
      from the der(10) and that the dmin and hsr were strongly positive for both genes.
      Southern blot analysis confirmed that both HMGIC and MDM2 were amplified and that
      no gross rearrangements of the genes had occurred. Immunostaining revealed that
      the HMGIC protein was highly overexpressed particularly in the large polymorphic
      cells within the carcinomatous part of the tumor. These findings suggest that
      amplification and overexpression of HMGIC and possibly MDM2 might be important
      genetic events that may contribute to malignant transformation of benign PA.

PMID- 11839564
TI  - Proteolytic cleavage of the CD44 adhesion molecule in multiple human tumors.
AB  - Cell surface adhesion molecules are crucial for the development and/or
      pathogenesis of various diseases including cancer. CD44 has received much
      interest as a major adhesion molecule that is involved in tumor progression. We
      have previously demonstrated that the ectodomain of CD44 undergoes proteolytic
      cleavage by membrane-associated metalloproteases in various tumor cell lines. The
      remaining membrane-bound CD44 cleavage product can be detected using antibodies
      against the cytoplasmic domain of CD44 (anti-CD44cyto antibody). However, the
      cleavage of CD44 in primary human tumors has not been investigated. Using Western
      blots with anti-CD44cyto antibody to assay human tumor tissues, we show that the
      CD44 cleavage product can be detected in 58% (42 of 72) of gliomas but not in
      normal brain. Enhanced CD44 cleavage was also found in 67% (28 of 42) of breast
      carcinomas, 45% (5 of 11) of non-small cell lung carcinomas, 90% (9 of 10) of
      colon carcinomas, and 25% (3 of 12) of ovarian carcinomas. Tumors expressing a
      CD44 splice variant showed a significantly higher incidence of enhanced CD44
      cleavage. The wide prevalence of CD44 cleavage suggests that it plays an
      important role in the pathogenesis of human tumors.

PMID- 11839566
TI  - Defective laminin 5 processing in cylindroma cells.
AB  - Cylindromas are benign skin tumors occurring as multiple nodules
      characteristically well circumscribed by an excess of basement membrane-like
      material. To determine the molecular defects leading to extracellular matrix
      accumulation, the ultrastructural, immunological, and biochemical properties of
      cylindroma tissue and isolated cells were analyzed. In cylindromas,
      hemidesmosomes are reduced in number, heterogeneous and immature compared to the
      normal dermal-epidermal junction. Expression of the alpha6beta4 integrin in tumor
      cells is weaker than in basal keratinocytes of the epidermis. Moreover, although
      in the epidermis alpha2beta1-integrin expression is restricted to the basal cell
      layer, it is found in all neoplastic cells within the nodules. Laminin 5 is
      present throughout the whole thickness of the basement membrane-like zone whereas
      laminin 10 is restricted to the interface adjacent to the tumor cells.
      Furthermore, laminin 5 is not properly processed and most of the alpha3A and
      gamma2 laminin chains remain as 165-kd and 155-kd polypeptides, respectively.
      Mature laminin 5 is thought to be necessary for correct hemidesmosome and
      basement membrane formation and its abnormal processing, as well as the low
      expression of alpha6beta4 integrins, could explain the lack of mature
      hemidesmosomes. Together, the results show that multiple molecular defects,
      including alteration of laminin 5 and its integrin receptors, contribute to
      structural aberrations of the basement membrane and associated structures in
      cylindromas.

PMID- 11839565
TI  - Evaluation of non-formalin tissue fixation for molecular profiling studies.
AB  - Using a general strategy for evaluating clinical tissue specimens, we found that
      70% ethanol fixation and paraffin embedding is a useful method for molecular
      profiling studies. Human prostate and kidney were used as test tissues. The
      protein content of the samples was analyzed by one-dimensional gel
      electrophoresis, immunoblot, two-dimensional gel electrophoresis, and layered
      expression scanning. In each case, the fixed and embedded tissues produced
      results similar to that obtained from snap-frozen specimens, although the protein
      quantity was somewhat decreased. Recovery of mRNA was reduced in both quantity
      and quality in the ethanol-fixed samples, but was superior to that obtained from
      formalin-fixed samples and sufficient to perform reverse transcription polymerase
      chain reactions. Recovery of DNA from ethanol-fixed specimens was superior to
      formalin-fixed samples as determined by one-dimensional gel electrophoresis and
      polymerase chain reaction. In conclusion, specimens fixed in 70% ethanol and
      embedded in paraffin produce good histology and permit recovery of DNA, mRNA, and
      proteins sufficient for several downstream molecular analyses. Complete protocols
      and additional discussion of relevant issues are available on an accompanying
      website (http://cgap-mf.nih.gov/).

PMID- 11839567
TI  - Stathmin-deficient mice develop an age-dependent axonopathy of the central and
      peripheral nervous systems.
AB  - Stathmin is a cytosolic protein that binds tubulin and destabilizes cellular
      microtubules, an activity regulated by phosphorylation. Despite its abundant
      expression in the developing mammalian nervous system and despite its high degree
      of evolutionary conservation, stathmin-deficient mice do not exhibit a
      developmental phenotype.(1) Here we report that aging stathmin(-/-) mice develop
      an axonopathy of the central and peripheral nervous systems. The pathological
      hallmark of the early axonal lesions was a highly irregular axoplasm
      predominantly affecting large, heavily myelinated axons in motor tracts. As the
      lesions progressed, degeneration of axons, dysmyelination, and an unusual glial
      reaction were observed. At the functional level, electrophysiology recordings
      demonstrated a significant reduction of motor nerve conduction velocity in
      stathmin(-/-) mice. At the molecular level, increased gene expression of SCG 10
      like protein, a stathmin-related gene with microtubule destabilizing activity,
      was detected in the central nervous system of aging stathmin(-/-) mice. Together,
      these findings suggest that stathmin plays an essential role in the maintenance
      of axonal integrity.

PMID- 11839568
TI  - Stat6-deficient mice develop airway hyperresponsiveness and peribronchial
      fibrosis during chronic fungal asthma.
AB  - Signal transducer and activator of transcription 6 (Stat6) is critical for Th2
      mediated responses during allergic airway disease. To investigate the role of
      Stat6 in fungus-induced airway hyperresponsiveness and remodeling, Stat6
      deficient (Stat6-/-) and Stat6-wildtype (Stat6+/+) mice were sensitized to
      Aspergillus fumigatus and airway disease was subsequently assessed in both groups
      at days 21, 30, 38, and 44 after an intratracheal challenge with live A.
      fumigatus conidia. At all times after conidia, histological analysis revealed an
      absence of goblet cell hyperplasia and markedly diminished peribronchial
      inflammation in Stat6-/- mice in contrast to Stat6+/+ mice. Airway
      hyperresponsiveness and peribronchial fibrosis in Stat6-/- mice were
      significantly reduced at day 21 after conidia compared with Stat6+/+ mice, but
      both groups exhibited significant, similar increases in these parameters at all
      subsequent times after conidia. In separate experiments, IL-13-responsive cells
      in Stat6-/- mice were targeted via the daily intranasal administration of 200 ng
      of IL-13-PE38QQR (IL13-PE), comprised of human IL-13 and a derivative of
      Pseudomonas exotoxin, from days 38 to 44 after the conidia challenge. IL13-PE
      treatment abolished airway hyperresponsiveness, but not peribronchial fibrosis in
      Stat6-/- mice. Taken together, these data demonstrate that the chronic
      development of airway hyperresponsiveness during fungal asthma is IL-13-dependent
      but Stat6-independent.

PMID- 11839569
TI  - Cytokeratins as targets for bile acid-induced toxicity.
AB  - Cholestasis is associated with retention of potentially toxic bile acids and
      profound cytoskeletal alterations of hepatocytes. Given the well-established
      cytoprotective role of hepatocyte keratins this study aimed to determine the
      effects of cholestasis on the cytokeratin (CK) intermediate filament network in
      mouse liver. Mice were subjected to common bile duct ligation or sham operation.
      Mice were also fed a cholic acid or ursodeoxycholic acid (UDCA)-supplemented diet
      (0.1%, 0.5%, and 1%) or control diet for 7 days. CK 8 and CK 18 expression was
      studied by competitive reverse transcriptase-polymerase chain reaction, in situ
      hybridization, Western blot analysis, and immunofluorescence microscopy. Common
      bile duct ligation and cholic acid feeding significantly stimulated CK 8 and CK
      18 mRNA and protein levels compared to controls, whereas UDCA had no effect. CK
      overexpression was accompanied by pronounced phosphorylation. Our results show
      that potentially toxic bile acids induce hepatocytic CK 8 and CK 18 expression
      and phosphorylation whereas nontoxic UDCA has no effect on CKs. Thus, increased
      hepatocellular CK expression and phosphorylation in cholestasis may be caused by
      retention of toxic bile acids and reflect a hepatocellular stress response with
      potential beneficial effects.

PMID- 11839570
TI  - Retinal vascular endothelial growth factor induces intercellular adhesion
      molecule-1 and endothelial nitric oxide synthase expression and initiates early
      diabetic retinal leukocyte adhesion in vivo.
AB  - Leukocyte adhesion to the diabetic retinal vasculature results in early blood
      retinal barrier breakdown, capillary nonperfusion, and endothelial cell injury
      and death. Previous work has shown that intercellular adhesion molecule-1 (ICAM
      1) and CD18 are required for these processes. However the relevant in vivo
      stimuli for ICAM-1 and CD18 expression in diabetes remain unknown. The current
      study investigated the causal role of endogenous vascular endothelial growth
      factor (VEGF) and nitric oxide in initiating these events. Diabetes was induced
      in Long-Evans rats with streptozotocin, resulting in a two- to threefold increase
      in retinal leukocyte adhesion. Confirmed diabetic animals were treated with a
      highly specific VEGF-neutralizing Flt-Fc construct (VEGF TrapA(40)). Retinal ICAM
      1 mRNA levels in VEGF TrapA(40)-treated diabetic animals were reduced by 83.5%
      compared to diabetic controls (n = 5, P < 0.0001). VEGF TrapA(40) also potently
      suppressed diabetic leukocyte adhesion in retinal arterioles (47%, n = 11, P <
      0.0001), venules (36%, n = 11, P < 0.0005), and capillaries (36%, n = 11, P <
      0.001). The expression of endothelial nitric oxide synthase (eNOS), a downstream
      mediator of VEGF activity, was increased in diabetic retina, and was potently
      suppressed with VEGF TrapA(40) treatment (n = 8, P < 0.005). Further, VEGF
      TrapA(40) reduced the diabetes-related nitric oxide increases in the retinae of
      diabetic animals. The inhibition of eNOS with N-omega-nitro-L-arginine methyl
      ester also potently reduced retinal leukocyte adhesion. Although neutrophil
      CD11a, CD11b, and CD18 levels were increased in 1-week diabetic animals, VEGF
      TrapA(40) did not alter the expression of these integrin adhesion molecules.
      Taken together, these data demonstrate that VEGF induces retinal ICAM-1 and eNOS
      expression and initiates early diabetic retinal leukocyte adhesion in vivo. The
      inhibition of VEGF bioactivity may prove useful in the treatment of the early
      diabetic retinopathy.

PMID- 11839571
TI  - Vitamin D arrests thyroid carcinoma cell growth and induces p27 dephosphorylation
      and accumulation through PTEN/akt-dependent and -independent pathways.
AB  - We investigated the effects of 1,25-dihydroxycholecalciferol vitamin D(3) (VD)
      and its noncalciomimetic analog EB1089 on thyroid carcinoma cell growth. VD and
      EB1089 exhibited anti-proliferative effects in a dose-dependent manner as
      determined by [(3)H]thymidine incorporation and MIB-1 immunolabeling. VD or
      EB1089 resulted in similar G(1)-phase arrest. Neither apoptosis nor
      differentiation was affected. VD and EB1089 induced increased nuclear protein
      expression of the cyclin-dependent kinase inhibitor, p27(kip1) (p27). VD/EB1089
      effects paralleled but were not additive to those of the proteasome inhibitor
      LLnL, consistent with reduced p27 degradation. As p27 phosphorylation and
      association with Skp2 is a key step in its degradation, we examined the effects
      of VD/EB1089 on this reaction. Despite increased total p27, the pThr content of
      p27 remained unaffected, an effect confirmed by diminished association with Skp2
      as well as in situ phosphorylation. Moreover, phosphatase inhibition abrogated
      the effect of VD/EB1089 on p27 accumulation consistent with a role for
      phosphatase action in mediating this VD effect. Although VD/EB1089 resulted in
      comparable increases in p27 in WRO and NPA cells, only WRO but not NPA cells
      demonstrated a change in the phosphatase PTEN and its downstream target pAkt/PKB
      in response to VD/EB1089. Transfection of PTEN resulted in p27 accumulation and
      was partially additive to the effect of VD/EB1089. Moreover, treatment with PI-3
      kinase inhibitors decreased pAkt/PKB and increased p27 in both WRO and NPA cells
      highlighting the potential role of this downstream pathway in regulating p27 in
      the thyroid. These findings point to a novel mechanism of action for VD/EB1089
      inhibition of thyroid carcinoma cell growth by p27 hypophosphorylation,
      diminished association with Skp2, and consequent accumulation. This effect can be
      mediated but is not essentially dependent on the phosphatase PTEN/Akt/PKB
      pathway. These properties support the potential utility of VD analogs in the
      treatment of thyroid carcinomas irrespective of their PTEN/pAkt status.

PMID- 11839572
TI  - Interferon-gamma reduces melanosomal antigen expression and recognition of
      melanoma cells by cytotoxic T cells.
AB  - In malignant melanoma, tumor-infiltrating lymphocytes are frequently reactive
      with melanosomal antigens. Achieving complete remissions by peptide therapy is
      frequently hampered by metastases evading immune recognition. The tumor
      microenvironment seems to favor reduced expression of target antigens by melanoma
      cells. Among candidate factors, interferon-gamma (IFN-gamma) (10(2) to 10(3)
      U/ml) suppressed expression of antigens MART-1, TRP-1, and gp100 by M14 melanoma
      cells as shown by immunohistology and fluorescence-activated cell sorting
      analysis, reducing MART-1 expression by >65%. Northern blot analysis revealed
      that reduced expression was regulated at the transcriptional level, demonstrating
      a 79% reduction in MART-1 transcript abundance after 32 hours of IFN-gamma
      treatment. To evaluate consequences of IFN-gamma exposure for immune recognition,
      MART-1-responsive T cells were reacted with pretreated HLA-matched melanoma
      cells. Cytotoxicity was reduced up to 78% by IFN-gamma pretreatment, and was
      restored by addition of MART-1 peptide AAGIGILTV for 2 hours. Examination of
      melanoma lesions by quantitative reverse transcriptase-polymerase chain reaction
      revealed up to 188-fold more abundant IFN-gamma transcripts when compared to
      control skin. Laser capture microdissection and immunohistology localized most
      IFN-gamma-producing T cells to the tumor stroma. Reduced MART-1 expression was
      frequently observed in adjacent tumor cells. Consequently, IFN-gamma may enhance
      inflammatory responses yet hamper effective recognition of melanoma cells.

PMID- 11839573
TI  - Concordant CpG island methylation in hyperplastic polyposis.
AB  - The CpG island methylator phenotype (CIMP) is a newly described mechanism for
      carcinogenesis in colorectal carcinomas and adenomas characterized by methylation
      of multiple CpG islands. The causes of CIMP are unknown. We studied CIMP in
      hyperplastic polyps (HPs), with emphasis on patients with multiple HPs (5 to 10
      HPs), large HPs (one HP >1 cm) or hyperplastic polyposis (>20 HPs). Methylation
      of p16, MINT1, MINT2, MINT31, and hMLH1 was analyzed by methylation-specific
      polymerase chain reaction in 102 HPs, 8 serrated adenomas, 19 tubular adenomas,
      and 9 adenocarcinomas from 17 patients, with multiple/large HPs or hyperplastic
      polyposis and in 16 sporadic HPs from 14 additional patients. Sporadic HPs were
      CIMP-negative (not methylated at any locus), but 43% of HPs from multiple/large
      HPs, or hyperplastic polyposis were CIMP-high (two or more methylated loci, P =
      0.00001). Methylation among the four loci was correlated within HPs (odds ratio,
      3.41; P = 0.002), and the methylation status of HPs within the same patient was
      also correlated (odds ratio, 5.92; P = 0.0001). CIMP-high HPs were present
      primarily in patients with a predominance of HPs in the right colon and/or
      serrated adenomas (P = 0.0009) and were associated with the absence of K-ras
      proto-oncogene mutations (odds ratio, 5.08; P = 0.03). Our findings of concordant
      CpG island methylation of HPs in multiple/large HPs or hyperplastic polyposis
      supports the concept that some patients have a hypermethylator phenotype
      characterized by methylation of multiple HPs and other colorectal lesions. The
      hypermethylator phenotype is related to patient-specific factors, such as
      carcinogenic exposure or genetic predisposition.

PMID- 11839574
TI  - Vascular endothelial growth factor-165 overexpression stimulates angiogenesis and
      induces cyst formation and macrophage infiltration in human ovarian cancer
      xenografts.
AB  - Vascular endothelial growth factor (VEGF) is suggested to be an important
      regulator of angiogenesis in ovarian cancer. We have evaluated the effects of
      VEGF overexpression on the histology and growth rate of human ovarian cancer
      xenografts. OVCAR-3 human ovarian cancer cells were stably transfected with an
      expression vector encoding the 165-amino acid isoform of VEGF. As subcutaneous
      xenografts, moderately and highly VEGF(165)-overexpressing OVCAR-3 cells formed
      tumors with large cysts. Immunohistochemistry demonstrated an increase in the
      number of CD31-positive microvessels, some of which were larger in diameter than
      those in the parental tumors, as well as extensive vascular rimming around the
      cysts. Weakly VEGF(165)-overexpressing tumors also contained an increased number
      of CD31-positive microvessels and occasional vascular rimming, but cysts were not
      present. Immunohistochemistry further revealed the presence of monocytes and
      macrophages in both parental and VEGF(165)-overexpressing xenografts.
      Interestingly, the number of monocytes/macrophages was greatly increased in
      moderately and highly VEGF(165)-overexpressing xenografts and large areas
      populated with monocytes/macrophages were detected within the tumor stroma.
      Although the higher number of CD31-positive cells would suggest a better
      vascularization pattern in VEGF(165)-overexpressing xenografts, tumor growth
      rates were not increased when compared with that of parental xenografts. These
      data provide functional evidence for a role of VEGF(165) in cyst formation and
      monocyte/macrophage infiltration.

PMID- 11839575
TI  - Versican is differentially expressed in human melanoma and may play a role in
      tumor development.
AB  - Undifferentiated human melanoma cell lines produce a large chondroitin sulfate
      proteoglycan, different from the well-known melanoma-specific proteoglycan mel-PG
      (Heredia and colleagues, Arch Biochem Biophys, 333: 198-206, 1996). We have
      identified this proteoglycan as versican and analyzed the expression of versican
      in several human melanoma cell lines. Versican isoforms are expressed in
      undifferentiated cell lines but not in differentiated cells, and the isoform
      expression pattern depends on the degree of cell differentiation. The V0 and V1
      isoforms are found on cells with an early degree of differentiation, whereas the
      V1 isoform is present in cells with an intermediate degree of differentiation. We
      have also characterized some functional properties of versican on human melanoma
      cells: the purified proteoglycan stimulates cell growth and inhibits cell
      adhesion when cells are grown on fibronectin or collagen type I as substrates,
      and thus may facilitate tumor cell detachment and proliferation. Furthermore, we
      have analyzed the expression of versican in human melanocytic nevi and melanoma:
      10 benign melanocytic nevi, 10 dysplastic nevi, 11 primary malignant melanomas,
      and 8 metastatic melanomas were tested. Immunoreactivity for versican was
      negative in benign melanocytic nevi, weakly to strongly positive in dysplastic
      nevi, and intensely positive in primary malignant melanomas and metastatic
      melanomas. Our results indicate that versican is involved in the progression of
      melanomas and may be a reliable marker for clinical diagnosis.

PMID- 11839576
TI  - CD40-CD40L interactions induce chemokine expression by human microglia:
      implications for human immunodeficiency virus encephalitis and multiple
      sclerosis.
AB  - CD40 is a protein on microglia that is up-regulated with interferon (IFN)-gamma
      and is engaged by CD40L, found on CD4+ T cells, B cells, and monocytes. These
      interactions may be important in central nervous system inflammatory diseases.
      Microglia have been shown to be a source of chemokines, whose expression plays a
      key role in central nervous system pathologies. We examined the expression of
      CD40 on microglia in human immunodeficiency virus (HIV) encephalitic brain, and
      the effects of CD40-CD40L interactions on the expression of chemokines by
      cultured microglia. We found significantly increased numbers of CD40-positive
      microglia in HIV-infected brain tissue. Treatment of cultured microglia with IFN
      gamma and CD40L increased expression of several chemokines. IFN-gamma- and CD40L
      induced MCP-1 protein was mediated by activation of the ERK1/2 MAPK pathway, and
      Western blot analysis demonstrated phosphorylation of ERK1/2 upon stimulation of
      microglia. In contrast, IFN-gamma- and CD40L-induced IP-10 protein production was
      mediated by the p38 MAPK pathway. Our data suggest a mechanism whereby CD40L+
      cells can induce microglia to secrete chemokines, amplifying inflammatory
      processes seen in HIV encephalitis and multiple sclerosis, and implicate CD40
      CD40L interactions as a target for interventional strategies.

PMID- 11839577
TI  - Nucleolar p14(ARF) overexpression in Reed-Sternberg cells in Hodgkin's lymphoma:
      absence of p14(ARF)/Hdm2 complexes is associated with expression of alternatively
      spliced Hdm2 transcripts.
AB  - The development of human cancers is frequently associated with the silencing of
      the two major tumor suppressor pathways represented by retinoblastoma protein and
      p53. As the incidence of p53 mutations is significantly lower in Hodgkin's
      lymphoma than in other neoplasias, we investigated whether the malfunction of
      other proteins in this pathway could be responsible for its inactivation. Because
      the existence of nucleolar complexes between p14(ARF) and Hdm2 has been described
      as having a critical effect on p53 function by inhibiting its degradation, we
      analyzed the expression and subcellular localization of these proteins in 52
      cases and in Hodgkin's cell lines. Two of four cell lines revealed loss of
      p14(ARF) expression secondary to gene promoter methylation, this being mutually
      exclusive with p53 mutations (1 of 4), illustrating the existence of selective
      pressure to inactivate the p53 pathway. The majority of Hodgkin's samples showed
      a strong nucleolar expression of p14(ARF) that was not associated with Hdm2. They
      also showed the existence of Hdm2/p53 complexes, and the absence of complexes
      containing either p14(ARF)/Hdm2 or p14(ARF)/p53. The different localization of
      Hdm2 (nucleoplasm) and p14(ARF) (nucleoli) observed in Hodgkin's tumors and cell
      lines is associated with the presence of short alternatively spliced transcripts
      of Hdm2 lacking the ARF-binding region and the nuclear export signal. The absence
      of these p14(ARF)/Hdm2 nucleolar complexes could be sufficient to inactivate the
      pathway and may explain the low frequency of p53 mutations in this tumor.

PMID- 11839578
TI  - Characterization of RhoC expression in benign and malignant breast disease: a
      potential new marker for small breast carcinomas with metastatic ability.
AB  - The most important factor in predicting outcome in patients with early breast
      cancer is the stage of the disease. There is no robust marker capable of
      identifying invasive carcinomas that despite their small size have a high
      metastatic potential, and that would benefit from more aggressive treatment. RhoC
      GTPase is a member of the Ras-superfamily and is involved in cell polarity and
      motility. We hypothesized that RhoC expression would be a good marker to identify
      breast cancer patients with high risk of developing metastases, and that it would
      be a prognostic marker useful in the clinic. We developed a specific anti-RhoC
      antibody and studied archival breast tissues that comprise a broad spectrum of
      breast disease. One hundred eighty-two specimens from 164 patients were used.
      Immunohistochemistry was performed on formalin-fixed tissues. Staining intensity
      was graded 0 to 3+ (0 to 1+ was considered negative and 2 to 3+ was considered
      positive). RhoC was not expressed in any of the normal, fibrocystic changes,
      atypical hyperplasia, or ductal carcinoma in situ, but was expressed in 36 of 118
      invasive carcinomas and strongly correlated with tumor stage (P = 0.01). RhoC had
      high specificity (88%) in detecting invasive carcinomas with metastatic
      potential. Of the invasive carcinomas smaller than 1 cm, RhoC was highly specific
      in detecting tumors that developed metastases. RhoC expression was associated
      with negative progesterone receptor and HER-2/neu overexpression. We
      characterized RhoC expression in human breast tissues. RhoC is specifically
      expressed in invasive breast carcinomas capable of metastasizing, and it may be
      clinically useful in patients with tumors smaller than 1 cm to guide treatment.

PMID- 11839579
TI  - Expression of functional interleukin-3 receptors on Hodgkin and Reed-Sternberg
      cells.
AB  - The human interleukin-3 receptor (IL-3R) is a heterodimeric complex consisting of
      an IL-3-specific alpha chain (IL-3Ralpha) and a common beta chain (beta(c)), this
      latter shared with the receptors for granulocyte-macrophage colony-stimulating
      factor and IL-5. Despite extensive research on cytokine circuitries regulating
      proliferation and survival of tumor cells in Hodgkin's disease (HD) the
      functional expression of IL-3Rs in this pathobiological entity has not yet been
      investigated. In the present study, we demonstrate that the great majority (>90%)
      of malignant Hodgkin and Reed-Sternberg cells of classic HD (19 of 19 analyzed
      cases) express IL-3Ralpha by immunostaining of frozen sections and cell
      suspensions from involved lymph nodes. Accordingly, HD cell lines (L428, KMH2,
      HDLM2, L1236) expressed the alpha and beta chains of IL-3R both at the mRNA and
      protein level, with a molecular size of IL-3Ralpha identical (70 kd) to that
      expressed by human myeloid cells. Exogenous IL-3 promoted the growth of cultured
      Hodgkin and Reed-Sternberg cells, such effect being potentiated by IL-9 co
      stimulation, and was able to partially rescue tumor cells from apoptosis induced
      by serum deprivation. This data suggests an involvement of IL-3/IL-3R
      interactions in the cellular growth of HD through paracrine mechanisms.

PMID- 11839580
TI  - Breast cancer risk in usual ductal hyperplasia is defined by estrogen receptor
      alpha and Ki-67 expression.
AB  - The hypothetical multistep model for breast carcinogenesis indicates that
      invasive carcinoma arises via a series of intermediate hyperplastic lesions
      through various grades of atypia to in situ and invasive carcinoma. Non-atypical
      hyperplasia [hyperplasia of usual type (HUT)] is a nonobligate precursor of
      breast cancer. Although its further morphological subclassification is unlikely,
      refining is more likely to depend on defining biological markers of risk. Having
      assembled a cohort of benign proliferative breast lesions of known outcome, we
      studied the expression of estrogen receptor-alpha (ER-alpha) and Ki-67 using
      morphometric image analysis as well as dual-labeled immunofluorescence in HUT
      foci and in surrounding normal lobules of 25 patients that progressed to breast
      cancer and 19 controls. Those patients that progressed to breast cancer (cases)
      showed significantly higher ER-alpha [median, 57.00% of cells within individual
      HUT foci; interquartile range (IQ), 33.48 to 67.78] and Ki-67 (median, 3.82%; IQ,
      0.85 to 11.28) expression in their HUT foci compared with controls (ER-alpha
      median, 30.27%; IQ, 19.75 to 52.50 and Ki-67 median, 0.77%; IQ, 0.0458 to 1.72, P
      = 0.008 and <0.001). No significant difference in expression of dual-stained
      cells was found between cases and controls. Although normal lobules from cases
      showed higher ER-alpha expression compared with controls, this was not
      statistically significant. Our data point to a previously undescribed hormone
      dependent pathway in this particular group of breast neoplasms and suggest the
      possibility of selective hormonal therapy to suppress the proliferative potential
      of these benign but high-risk breast lesions. The findings of this study might
      have important implications for improving breast cancer screening and management
      strategies.

PMID- 11839581
TI  - Quantitative assessment of promoter hypermethylation during breast cancer
      development.
AB  - The aberrant methylation of cytosine residues in the promoter region of growth
      regulatory genes is now widely recognized as an additional mechanism for gene
      inactivation in cancer cells. In this study we analyzed the methylation status of
      four growth regulatory genes (p16, RASSF1A, cyclinD2, 14-3-3zeta) during breast
      cancer progression. For this purpose invasive and noninvasive tumor cell
      populations as well as hyperplastic cell proliferations were isolated from a
      series of archival breast tissue specimens (n = 57) using laser-assisted
      microdissection. A new real-time polymerase chain reaction-based assay was used
      for the sensitive and quantitative determination of the cell-specific methylation
      status. We found that aberrant promoter methylation was already prevalent in pure
      intraductal carcinoma with different frequencies and different methylation levels
      for the four genes analyzed. For RASSF1A and 14-3-3zeta promoter methylation was
      also demonstrated in epithelial hyperplasia and intraductal papillomas. By
      contrast, aberrant methylation of cyclinD2 and p16 was restricted to cancerous
      epithelium. Increased methylation of the cyclinD2 gene was significantly
      associated with a higher van Nuys grade. Furthermore, when intraductal and
      invasive tumor cells were compared, significant quantitative changes in the
      methylation level were detected primarily within the cyclinD2 gene. These results
      demonstrate that promoter methylation is an early and frequent event in breast
      cancer development, but displays great quantitative and gene-specific
      differences, and changes in a gene-specific manner during tumor progression.

PMID- 11839582
TI  - Hepatocyte growth factor and c-Met inhibition by hepatic cell hypoxia: a
      potential mechanism for liver regeneration failure in experimental cirrhosis.
AB  - Hepatic resection in cirrhotic patients is associated with impaired liver
      regeneration and poor clinical outcome. Because experimental cirrhosis is
      associated with hepatic cell hypoxia, we herein investigated whether hypoxia
      might alter the mechanisms of liver regeneration in the cirrhotic liver.
      Cirrhosis was induced by diethylnitrosamine in rats. Immunohistochemistry was
      performed to assess hepatocellular hypoxia and proliferation 24 hours after a two
      thirds partial hepatectomy (PH) in cirrhotic and control rats. Cultured
      hepatocytes and myofibroblastic hepatic stellate cells were submitted to hypoxia
      using anaerobic jars. Hepatocyte growth factor (HGF) and c-Met expressions were
      determined by reverse transcriptase-polymerase chain reaction, Northern blot, and
      Western blot. In control rats, hypoxia was restricted to perivenular hepatocytes,
      and PH induced a marked increase in hepatocyte proliferation and in liver HGF
      expression, whereas c-Met expression remained unchanged. In cirrhotic rats,
      hypoxia was detected virtually in all of the hepatocytes, and PH induced no
      significant change in hepatocyte proliferation and in liver HGF expression,
      whereas c-Met expression was decreased as compared to normal livers. In vitro,
      the expression of HGF in myofibroblastic hepatic stellate cells and of c-Met in
      hepatocytes underwent a dramatic decrease under hypoxia. Our results suggest that
      hepatocellular hypoxia causes inhibition of HGF (and of c-Met)-mediated
      proliferation and thereby might contribute to liver regeneration failure in
      cirrhotic liver.

PMID- 11839583
TI  - Beta1 and beta2 integrins mediate adhesion during macrophage fusion and
      multinucleated foreign body giant cell formation.
AB  - An in vitro system of interleukin (IL)-4-induced human monocyte-derived
      macrophage fusion was used to investigate the cell/substrate adhesive mechanisms
      that support multinucleated foreign body giant cell (FBGC) formation. Monocytes
      were cultured for 3 days and IL-4 was added to induce macrophage fusion and FBGC
      formation by day 7. Functionally defined anti-integrin antibodies demonstrated
      that initial monocyte adhesion is mediated by beta2 integrins, whereas during the
      induction of macrophage fusion by IL-4, an additional dependence on beta1
      integrins is acquired. The combination of anti-beta1 plus anti-beta2 was most
      effective, reducing macrophage/FBGC adhesion to 10% of controls. Consistent with
      integrin-mediated signaling, the tyrosine kinase inhibitor genistein and the
      phosphatidylinositol-3-kinase inhibitors wortmannin and LY294002 also attenuated
      macrophage/FBGC adhesion. Confocal microscopic analysis revealed that beta2
      integrins are present on monocytes after initial adhesion and are strongly
      expressed on fusing macrophages, particularly in peripheral cell areas, and on
      FBGCs. In contrast, beta1 integrins are not detected on monocytes but begin to
      appear during macrophage development and are strongly expressed on fusing
      macrophages and FBGCs. For the first time, these results demonstrate the IL-4
      induced acquisition of cooperation between beta1 and beta2 integrins in the
      cell/substrate adhesive interactions that are required for multinucleated FBGC
      formation.

PMID- 11839584
TI  - DeltaN-p73alpha accumulates in human neuroblastic tumors.
AB  - Neuroblastic tumors (NTs), occurring in early childhood, display a wide spectrum
      of differentiation. Recurrent deletions involving the p73 locus are frequently
      observed in undifferentiated NTs. To address the question of the possible
      implication of p73 in neuroblastic differentiation, we investigated the status of
      the expression of this gene in a panel of differentiated and undifferentiated
      tumors. Although mutations were not found, p73 transcript profiles differed
      between undifferentiated and differentiated tumors. The frequency of the
      transcripts lacking exon 2 (species 1-3) appeared to be higher in
      undifferentiated than in differentiating and differentiated NTs. In contrast,
      products from using an alternate promoter (DeltaN-p73) were present in all NTs.
      In addition, only DeltaN-p73, but not full-length proteins, were detected by
      immunoblotting, suggesting a greater stability of N-truncated isoforms.
      Importantly, as in the adrenal medulla, most NTs showed p73-positive
      immunohistological staining with a cellular distribution and intensity varying
      according to the neuronal differentiation. Surprisingly, we observed
      redistribution of p73 from the nucleus to the cytoplasm during neuroblastic
      differentiation. Our data suggest that, in undifferentiated NTs, a link may exist
      between the accumulation of DeltaN-p73alpha variants and the "nuclear exclusion"
      of p53.

PMID- 11839586
TI  - Axonal injury in cerebral malaria.
AB  - Impairment of consciousness and other signs of cerebral dysfunction are common
      complications of severe Plasmodium falciparum malaria. Although the majority of
      patients make a complete recovery a significant minority, particularly children,
      have sequelae. The pathological process by which P. falciparum malaria induces
      severe but usually reversible neurological complications has not been elucidated.
      Impairment of transport within nerve fibers could induce neurological dysfunction
      and may have the potential either to resolve or to progress to irreversible
      damage. Beta-amyloid precursor protein (beta-APP) immunocytochemistry, quantified
      using digital image analysis, was used to detect defects in axonal transport in
      brain sections from 54 Vietnamese cases with P. falciparum malaria. The frequency
      and extent of beta-APP staining were more severe in patients with cerebral
      malaria than in those with no clinical cerebral involvement. Beta-APP staining
      was often associated with hemorrhages and areas of demyelination, suggesting that
      multiple processes may be involved in neuronal injury. The age of focal axonal
      damage, as determined by the extent of the associated microglial response, varied
      considerably within tissue sections from individual patients. These findings
      suggest that axons are vulnerable to a broad range of cerebral insults that occur
      during P. falciparum malaria infection. Disruption in axonal transport may
      represent a final common pathway leading to neurological dysfunction in cerebral
      malaria.

PMID- 11839585
TI  - Insights into the pathobiology of hepatitis C virus-associated cirrhosis:
      analysis of intrahepatic differential gene expression.
AB  - The pathogenesis of hepatitis C virus (HCV)-associated liver injury involves many
      genes from multiple pathogenic pathways. cDNA array analysis, which examines the
      expression of many genes simultaneously, was used to achieve new insights into
      HCV liver injury. Membrane-based cDNA arrays of 874 genes compared HCV-associated
      cirrhosis with autoimmune hepatitis-associated cirrhosis as an inflammatory and
      cirrhotic control, and with nondiseased liver tissue. Array analysis identified
      many differentially expressed genes that are important in inflammation, fibrosis,
      proliferation, signaling, apoptosis, and oxidative stress. Genes up-regulated in
      HCV-associated cirrhosis were predominantly associated with a Th1 immune
      response, fibrosis, cellular proliferation, and apoptosis. Novel observations of
      differential gene expression included increased expression of secreted apoptosis
      related protein 3, a Wnt pathway gene possibly involved in cellular apoptosis.
      EMMPRIN (CD147) and discoidin domain receptor 1 (CD167) were also shown to be
      increased and are likely to play a role in liver fibrosis. Real-time quantitative
      reverse transcriptase-polymerase chain reaction confirmed the increased
      expression of 15 genes. The comparison of HCV cirrhosis with autoimmune hepatitis
      cirrhosis showed a marked difference in the apoptosis-associated gene profile
      with HCV cirrhosis characterized by increased proapoptotic gene expression
      whereas autoimmune hepatitis was characterized by increased expression of both
      antiapoptotic and proapoptotic genes. Furthermore, expression of beta-catenin and
      the fibrosis-associated protein EMMPRIN were localized by immunohistochemistry to
      the plasma membranes of hepatocytes and biliary epithelium. In conclusion, HCV
      associated cirrhosis was characterized by a proinflammatory, profibrotic, and
      proapoptotic gene expression profile.

PMID- 11839587
TI  - Expression of group IIA secretory phospholipase A2 is elevated in prostatic
      intraepithelial neoplasia and adenocarcinoma.
AB  - Phospholipase A2 (PLA2) enzymes release arachidonic acid from cellular
      phospholipids in a variety of mammalian tissues, including prostate. Group IIa
      secretory PLA2 (sPLA2) can generate arachidonate from cellular phospholipids. We
      examined the group IIa sPLA2 expression in benign prostatic tissues, prostatic
      intraepithelial neoplasia (PIN), and adenocarcinoma to determine whether sPLA2
      expression is altered in the carcinogenesis of human prostatic cancer. Thirty
      three of 74 total cases (45%) of benign prostatic tissue showed positive
      immunohistochemical staining for group IIA sPLA2, whereas 63 of 69 total cases
      (91%) of high-grade PINs and 70 of 78 total cases (90%) of adenocarcinomas gave
      positive results. Four of 10 cases of low-grade PIN showed positive
      immunoreactivity for sPLA2. The number of cells staining for sPLA2 was
      significantly less in benign epithelium (4%) and low-grade PIN (4%) compared to
      high-grade PIN (40%) or adenocarcinoma (38%) (P < 0.001). There was no
      significant difference between high-grade PIN and adenocarcinoma in the number of
      cells staining positively for sPLA2. The intensity of sPLA2 immunoreactivity was
      also different among benign prostatic tissue, low-grade PIN, high-grade PIN, and
      prostatic adenocarcinoma specimens. The malignant cells demonstrated more intense
      immunohistochemical staining (moderate to strong staining in 81% and 69% cases
      for high-grade PIN and adenocarcinoma, respectively) than benign glands (moderate
      staining in 11% of cases). No strong staining was observed in benign glands or
      low-grade PIN. Our data are consistent with the contention that group IIA sPLA2
      expression is elevated in neoplastic prostatic tissue and support the hypothesis
      that dysregulation of sPLA2 may play a role in prostatic carcinogenesis.

PMID- 11839588
TI  - Shedding of the matrix metalloproteinases MMP-2, MMP-9, and MT1-MMP as membrane
      vesicle-associated components by endothelial cells.
AB  - Production of matrix-degrading proteases, particularly matrix metalloproteinases
      (MMPs), by endothelial cells is a critical event during angiogenesis, the process
      of vessel neoformation that occurs in normal and pathological conditions. MMPs
      are known to be highly regulated at the level of synthesis and activation,
      however, little is known about the regulation of MMP secretion by endothelial
      cells. We found that cultured human umbilical vein endothelial cells shed
      vesicles (300 to 600 nm) originating from localized areas of the cell plasma
      membrane, as revealed by ultrastructural analysis. Normal and reverse zymography,
      Western blot, and immunogold analyses of the vesicles showed two gelatinases, MMP
      2 and MMP-9, in both the active and proenzyme forms, the MT1-MMP proenzyme
      located on the external side of the vesicle membrane and the two inhibitors TIMP
      1 and TIMP-2. Serum and the angiogenic factors, fibroblast growth factor-2 and
      vascular endothelial growth factor, stimulated the shedding of MMPs as vesicle
      components. Shedding the vesicle was rapid, as it was already completed after 4
      hours. Addition of shed vesicles to human umbilical vein endothelial cells
      resulted in autocrine stimulation of invasion through a layer of reconstituted
      basement membrane (Matrigel) and cord formation on Matrigel. We conclude that
      endothelial cells shed MMP-containing vesicles and this may be a mechanism for
      regulating focalized proteolytic activity vital to invasive and morphogenic
      events during angiogenesis.

PMID- 11839590
TI  - Transfection of S100A4 produces metastatic variants of an orthotopic model of
      bladder cancer.
AB  - The calcium-binding protein S100A4 induces the metastatic phenotype in rodent
      models of breast cancer, and its expression strongly correlates with reduced
      survival in human breast and bladder cancer. We have established an orthotopic
      model of bladder cancer by injecting a cell line derived from a carcinogen
      induced rat bladder tumor into the muscular wall of syngeneic rats. MYU-3L cells
      produce rapidly growing, invasive tumors in the bladder wall but they fail to
      metastasize. Transfection of MYU-3L cells with a plasmid vector directing
      overexpression of the S100A4 gene generates variants in which S100A4 expression
      is elevated by up to sevenfold in comparison with the untransfected cells.
      Variants overexpressing S100A4 produce primary tumors at similar frequencies and
      latencies to the parental cell line, a significant number of which metastasize to
      the para-aortic lymph nodes or lungs. Expression of S100A4 protein in the primary
      tumors was heterogeneous, but was stronger and more consistent in the metastases,
      suggesting that transfectants overexpressing S100A4 possess an enhanced ability
      to form metastatic lesions. We conclude that overexpression of S100A4 can induce
      the metastatic phenotype in this rodent model of bladder cancer. Taken together
      with the results from our parallel studies of human bladder cancer, these data
      suggest a significant role for S100A4 in bladder cancer metastasis and identify a
      potential new target for systemic therapy in patients with this disease.

PMID- 11839589
TI  - Stimulation of mesothelial cell proliferation by exudate macrophages enhances
      serosal wound healing in a murine model.
AB  - Examination of thermally induced serosal lesions in mice displayed collections of
      inflammatory cells, predominantly macrophages, on and surrounding the wound
      within 48 hours of injury. Furthermore, by 2 days a large number of uninjured
      mesothelial cells adjacent to the wound were synthesizing DNA. From these
      findings, it was hypothesized that macrophages play a major role in serosal
      repair by stimulating mesothelial cell proliferation. Again, using a murine model
      of mesothelial regeneration, depletion of circulating monocytes significantly
      delayed serosal healing whereas addition of peritoneal exudate cells to the wound
      site 36 hours before injury increased the healing rate. In vivo assessment of
      mesothelial cell proliferation using tritiated thymidine incorporation and
      autoradiography demonstrated that peritoneal exudate cells stimulated mesothelial
      cell proliferation (12.44 +/- 1.63% labeling index, compared with controls in
      which medium only was used 4.48 +/- 0.71%). The mesothelial proliferation was
      predominantly because of macrophage-secreted products with molecular weights of
      36 to 53 kd or 67 to 100 kd. These data support the hypothesis that macrophages
      play an important role in serosal healing by stimulating mesothelial cell
      proliferation.

PMID- 11839591
TI  - Disease stage-dependent accumulation of lipid and protein oxidation products in
      human atherosclerosis.
AB  - Oxidative modification of low-density lipoprotein is thought to promote arterial
      lipid accumulation and atherogenesis. Previous studies reported on the presence
      of certain lipid or protein oxidation products in lesions, although a systematic
      investigation measuring several oxidation parameters and the accumulation of
      nonoxidized lipids and antioxidants at various stages of atherosclerosis has not
      been performed in the same tissue. Using the intimal lipoprotein-containing
      fraction of human aortic lesions, we demonstrate here that cholesterol
      accumulated with lesion development and that this increase was already
      significant at the fatty streak stage. By comparison, cholesterylesters increased
      significantly only in fibro-fatty and more complex lesions that also contained
      significantly increased amounts of cholesterylester hydro(pero)xides and 27
      hydroxycholesterol. Cholesterylester hydroxides were the major lipid oxidation
      product detected. Despite accumulation of oxidized lipid, alpha-tocopherol was
      also present and maintained at a comparable level over the disease process. Of
      the oxidized protein moieties measured only o,o-dityrosine increased with
      disease, although chlorotyrosines were present at relatively high levels in all
      lesions compared to healthy vessels. Our data show that accumulation of
      nonoxidized lipid precedes that of oxidized lipid in human aortic lesions.

PMID- 11839592
TI  - Inducible expression of vascular endothelial growth factor in adult mice causes
      severe proliferative retinopathy and retinal detachment.
AB  - Transgenic mice with vascular endothelial growth factor (VEGF) driven by the
      rhodopsin promoter (rho/VEGF mice) develop neovascularization that originates
      from the deep capillary bed of the retina and grows into the subretinal space. In
      rho/VEGF mice, VEGF expression in photoreceptors begins between postnatal days 5
      and 7, the period when the deep capillary bed is developing. An important
      question is whether or not the developmental stage of the deep capillary bed is
      critical for occurrence of neovascularization. Also, although rho/VEGF mice are
      extremely useful for the study of ocular neovascularization, there are some
      applications for which the early onset of VEGF expression is a disadvantage. In
      this study, we used the reverse tetracycline transactivator (rtTA) inducible
      promoter system coupled to either the rhodopsin or interphotoreceptor retinoid
      binding protein (IRBP) promoter to control the time of onset of VEGF transgene
      expression in photoreceptors. In the absence of doxycycline, adult double
      transgenic rho/rtTA-TRE/VEGF or IRBP/rtTA-TRE/VEGF mice showed little VEGF
      transgene expression and no phenotype. The addition of doxycycline to the
      drinking water resulted in prominent transgene expression and evidence of
      neovascularization within 3 to 4 days. Like rho/VEGF mice, the neovascularization
      originated from the deep capillary bed of the retina, but it was more extensive
      and caused outer retinal folds followed by total retinal detachment. Real-time
      polymerase chain reaction and enzyme-linked immunosorbent assay demonstrated that
      the mice with inducible expression of VEGF that developed retinal detachment had
      much higher ocular levels of VEGF mRNA and protein compared to rho/VEGF mice that
      manifest a much milder phenotype. These data demonstrate that regardless of
      developmental stage of the vascular bed, increased expression of VEGF in the
      retina is sufficient to cause neovascularization, and high levels of expression
      cause severe neovascularization and traction retinal detachment. Mice with
      inducible expression of VEGF in the retina provide a valuable new model of ocular
      neovascularization.

PMID- 11839593
TI  - Quantitative trait loci influence renal disease progression in a mouse model of
      Alport syndrome.
AB  - Alport syndrome is a human hereditary glomerulonephritis which results in end
      stage renal failure (ESRF) in most cases. It is caused by mutations in any one of
      the collagen alpha3(IV), alpha4(IV), or alpha5(IV) chain genes (COL4A3-COL4A5).
      Patients carrying identical mutations can exhibit very different disease courses,
      suggesting that other genes or the environment influence disease progression. We
      previously generated a knockout mouse model of Alport syndrome by mutating
      Col4a3. Here, we show that genetic background strongly influences the timing of
      onset of disease and rate of progression to ESRF in these mice. On the 129X1/SvJ
      background, Col4a3 -/- mice reached ESRF at approximately 66 days of age, while
      on the C57BL/6J background, the mean age at ESRF was 194 days of age. This
      suggests the existence of modifier genes that influence disease progression. A
      detailed histopathological analysis revealed that glomerular basement membrane
      lesions typical of Alport syndrome were significantly more frequent in
      homozygotes on the 129X1/SvJ background than on the C57BL/6J background as early
      as two weeks of age, suggesting that modifier genes act by influencing glomerular
      basement membrane structure. Additional data indicated that differential
      physiological responses to basement membrane splitting also underlie the
      differences in disease progression. We attempted to map the modifier genes as
      quantitative trait loci (QTLs) using age at ESRF as the quantitative trait.
      Genome scans were performed on mice at the two extremes in a cohort of mutant F1
      x C57BL/6J backcross mice. Analysis with Map Manager QT revealed QTLs linked to
      markers on chromosomes 9 and 16. A more detailed understanding of how these QTLs
      act could lead to new approaches for therapy in diverse renal diseases.

PMID- 11839596
TI  - Intrinsic signals and functional brain mapping: caution, blood vessels at work.

PMID- 11839595
TI  - Helicobacter bilis infection accelerates and H. hepaticus infection delays the
      development of colitis in multiple drug resistance-deficient (mdr1a-/-) mice.
AB  - mdr1a-deficient mice lack P-glycoprotein and spontaneously develop colitis with
      age. Helicobacter spp. are gram-negative organisms that have been associated with
      colitis in certain mouse strains, but Helicobacter spp. have been excluded as
      contributing to the spontaneous colitis that develops in mdr1a-/- mice. We wished
      to determine whether infection with either H. bilis or H. hepaticus would
      accelerate the development of inflammatory bowel disease (IBD) in mdr1a-/- mice.
      We found that H. bilis infection induced diarrhea, weight loss, and IBD in mdr1a
      /- mice within 6 to 17 weeks post-inoculation and before the expected onset of
      spontaneous IBD. Histopathology of H. bilis-induced IBD included crypt
      hyperplasia, inflammatory cell infiltrates, crypt abscesses, and obliteration of
      normal gut architecture. Reverse transcription-polymerase chain reaction and
      Taqman analysis from colonic tissue showed increased transcripts for interferon
      gamma and interleukin-10 from H. bilis-infected colitic mdr1a-/- mice.
      Additionally, mesenteric lymph nodes had increased cellularity with expansion of
      CD4+ and CD8+ T cells and B cells and increased proliferation to soluble H. bilis
      antigens with elaboration of interferon-gamma, tumor necrosis factor-alpha and
      interleukin-10. In contrast, H. hepaticus infection of mdr1a-/- mice did not
      accelerate disease but rather delayed the onset of spontaneous colitis which was
      milder in severity. mdr1a-/- mice infected with Helicobacter spp. may provide a
      useful tool to explore the pathogenesis of microbial-induced IBD in a model with
      a presumed epithelial cell "barrier" defect.

PMID- 11839594
TI  - Stable beta-secretase activity and presynaptic cholinergic markers during
      progressive central nervous system amyloidogenesis in Tg2576 mice.
AB  - We examined presynaptic cholinergic markers and beta-secretase activity during
      progressive central nervous system amyloidogenesis in Tg2576 Alzheimer mice
      (transgenic for human amyloid precursor protein Swedish mutation; hAPPswe). At
      14, 18, and 23 months of age there were no significant differences between wild
      type and transgenic mice in four distinct central nervous system cholinergic
      indices--choline acetyltransferase and acetylcholinesterase activities, and
      binding to vesicular acetylcholine transporter and Na(+)-dependent high-affinity
      choline uptake sites. A novel enzyme-linked immunosorbent assay measuring only
      the secreted human beta-secretase cleavage product (APPsbetaswe) of APPswe also
      revealed no change with aging in Tg2576 mouse brain. In contrast, transgenic but
      not wild-type mice exhibited an age-dependent increase in soluble Abeta40 and
      Abeta42 levels and progressive amyloid deposition in brain. Thus, aging Tg2576
      mice exhibited presynaptic cholinergic integrity despite progressively increased
      soluble Abeta40 and Abeta42 levels and amyloid plaque density in brain. Older
      Tg2576 mice may best resemble preclinical or early stages of human Alzheimer's
      disease with preserved presynaptic cholinergic innervation. Homeostatic
      APPsbetaswe levels with aging suggest that progressive amyloid deposition in
      brain results not from increased beta-secretase cleavage of APP but from impaired
      Abeta/amyloid clearance mechanisms.

PMID- 11839597
TI  - Blood capillary distribution correlates with hemodynamic-based functional imaging
      in cerebral cortex.
AB  - Our study concerns the mechanisms that underlie functional imaging of sensory
      areas of cortex using hemodynamic-based methods such as optical imaging of
      intrinsic signals, functional magnetic resonance imaging and positron emission
      tomography. In temporal cortex of chinchilla, we have used optical imaging of
      intrinsic signals evoked by acoustic stimulation to define the functionally
      responsive area and then made (scanning electron microscopy) observations of the
      corresponding capillary networks prepared by corrosion cast methods. We report
      that intrinsic signals associated with auditory cortex correlate directly with
      discrete capillary beds. These capillary beds, within the cortical surface
      layers, are distributed across the cortex in a non-uniform fashion. Within cortex
      both the arterial supply and the capillary network contain various flow control
      structures. Our study suggests a causal relationship between the metabolic
      demands of local neuronal activity and both the density of the capillary network
      and the placement of the control structures. Such relationships will affect the
      ultimate spatial resolution obtainable by hemodynamic-based functional brain
      imaging studies. These relationships will also affect quantitative comparisons of
      activity levels in different areas of cortex.

PMID- 11839599
TI  - Prefrontal cortex and dynamic categorization tasks: representational organization
      and neuromodulatory control.
AB  - We present a computational model of the intradimensional/ extradimensional
      (ID/ED) task (a variant of the Wisconsin card sorting task) that simulates the
      performance of intact and frontally lesioned monkeys on three different kinds of
      rule changes (Dias et al., 1997, J Neurosci 17:9285-9297). Although Dias et al.
      interpret the lesion data as supporting a model in which prefrontal cortex is
      organized into different processing functions, our model suggests an alternative
      account based on representational content. A key aspect of the model is that
      prefrontal cortex representations are organized according to different levels of
      abstraction, with orbital areas encoding more specific featural information and
      dorsolateral areas encoding more abstract dimensional information. This
      representational scheme of the model is integrated with two additional key
      elements: (i) activation-based working memory representations controlled by a
      dynamic gating mechanism that simulates the hypothesized phasic actions of
      dopaminergic neuromodulation in prefrontal cortex, which acts to stabilize or
      destabilize frontal representations based on success in the task; and (ii) a
      weight-based associative learning system simulating posterior cortex and other
      subcortical areas, where the stimulus-response mappings are encoded. Frontal
      cortex contributes to the task via top-down activation-based biasing of task
      appropriate features and dimensions in this posterior cortex system - this top
      down biasing is specifically important for overcoming prepotent associations
      after a sorting rule reverses. The ability of the model to capture the double
      dissociation observed by Dias et al. with orbital versus dorsolateral lesions
      supports the validity of these principles, many of which have also been useful in
      accounting for other frontal phenomena.

PMID- 11839598
TI  - Visual receptive field modulation in the lateral intraparietal area during
      attentive fixation and free gaze.
AB  - The receptive field (RF) of neurons recorded from the lateral intraparietal area
      (LIP) was quantified using a rapid, computer-driven mapping procedure. For each
      neuron, the RF was mapped: (1) during attentive fixation and (2) during free
      visual exploration. RF location, size and internal structure were modulated by
      the mapping context in over two-thirds of the recorded neurons. The major trend
      was a proportionally larger amount of neuronal visual resources allocated to
      central space during fixation, and an attenuated center-to-periphery gradient in
      the visual field representation during free gaze. A population approach shows
      that these spatial modulations are accompanied by changes in the signal-to-noise
      ratio of the information carried in the RF substructure. We related these
      neurophysiological observations to behavior, by comparing the characteristics of
      saccades elicited during fixation and free gaze. Together, the results suggest
      that the dynamics of LIP visual RFs may characterize both the state of engagement
      of attention and the power of resolution of visual analysis: during fixation, the
      neural population is locked in a filter state concentrating the processing
      resources at the fovea, while during free gaze, the population shifts to a
      detector state spreading the resources more evenly across the visual field.

PMID- 11839600
TI  - Impaired facial affect recognition and emotional changes in subjects with
      transmodal cortical lesions.
AB  - The present study attempts to identify cortical lesion sites associated with
      deficits in the decoding of emotional facial expressions and with changes of
      emotional states. A consecutive sample of 68 subjects with lesions caused by
      microsurgical tumor resection or by intracerebral hemorrhage were compared with
      16 clinical and 15 healthy control subjects. A set of neuropsychological test
      measures - two experimental tasks requiring the sorting and rating of emotional
      facial expressions, and an adjective checklist as a measure of mood state - were
      administered. An analysis according to the functional properties of the areas
      with lesions revealed that subjects with combined lesions of heteromodal and
      limbic/ paralimbic cortices of the right hemisphere showed the strongest deficits
      in the decoding of emotional facial expressions. In contrast, subjects with
      lesions of limbic/paralimbic cortices alone, or subjects with lesions of unimodal
      or primary motor or sensory cortices displayed only minor deficits. Subjects with
      combined lesions of heteromodal and limbic/paralimbic cortices of the left
      hemisphere showed the most negative mood states. Our results suggest that
      heteromodal and limbic/paralimbic, i.e. transmodal cortices may be viewed as
      'bottleneck' structures for the decoding of emotional facial expressions and for
      the modulation of mood states. Lesions of transmodal cortices deprive limbic
      structures of one of their main sources of input and are therefore likely to
      produce deficits in various forms of complex human emotional-cognitive behaviors
      and emotional states.

PMID- 11839601
TI  - Intraoperative intrinsic optical imaging of neuronal activity from subdivisions
      of the human primary somatosensory cortex.
AB  - We performed intrinsic optical imaging of neuronal activity induced by peripheral
      stimulation from the human primary somatosensory cortex during brain tumor
      surgery for 11 patients. After craniotomy and dura reflection, the cortical
      surface was illuminated with a xenon light through an operating microscope. The
      reflected light passed through a bandpass filter, and we acquired functional
      images using an intrinsic optical imaging system. Electrical stimulation of the
      median nerve, or the first and fifth digits, induced biphasic intrinsic optical
      signals which consisted of a decrease in light reflectance followed by an
      increase. The decrease in light reflectance was imaged, and we identified a
      neural response area within the crown of the postcentral gyrus. In experiments on
      first and fifth digit stimulation, we identified optical responses in separated
      areas within the crown of the postcentral gyrus, i.e. near the central sulcus and
      near the postcentral sulcus. In the former response area, separate
      representations of the two fingers were observed, whereas in the latter response
      area, the two fingers were represented in the same region. A similar somatotopic
      representation was observed with electrical stimulation of the first and third
      branches of the trigeminal nerve. These results seem to support the hypothesis of
      hierarchical organization in the human primary somatosensory cortex.

PMID- 11839602
TI  - Differences in the corticospinal projection from primary motor cortex and
      supplementary motor area to macaque upper limb motoneurons: an anatomical and
      electrophysiological study.
AB  - To further our understanding of the functional roles of different motor cortical
      areas, we made a quantitative comparison of the density of corticospinal
      projections from primary motor cortex (M1) and supplementary motor area (SMA) to
      spinal motor nuclei supplying hand and finger muscles in four macaque monkeys. We
      also compared the action of corticospinal outputs excited by electrical
      stimulation of these two areas on upper limb motoneurons recorded in three
      anaesthetized macaques. The hand representations of SMA and M1 were first
      identified using structural magnetic resonance imaging scans and intracortical
      microstimulation. In the anatomical study we then made focal injections of
      wheatgerm agglutinin- horseradish peroxidase into these representations, which
      were subsequently confirmed by analysis of retrograde cortical labelling.
      Densitometric analysis showed that corticospinal projections from M1 were denser
      and occupied a greater proportion of the hand muscle motor nuclei than did
      projections from SMA. In caudal Th1 the densest projections from M1 occupied 81%
      of this motoneuronal area, compared with only 6% from SMA. In the
      electrophysiological study, bipolar intracortical stimulation of the hand
      representation of M1 and SMA evoked direct (D) and indirect (I) corticospinal
      volleys. Volleys elicited by M1 stimulation had larger amplitudes and faster
      conduction velocities than those evoked from the SMA. Intracellular recordings
      were made from 84 contralateral upper limb motoneurons. M1 and SMA stimulation
      evoked markedly different responses in tested motoneurons: EPSPs were larger and
      more common from M1 (88% of motoneurons) than from SMA (48%). Some motoneurons
      (16/84) showed evidence of excitatory postsynaptic potentials mediated by
      monosynaptic action of the D-wave evoked from M1; these early effects were not
      observed from the SMA. In most motoneurons (74/84) EPSPs had segmental latencies
      indicating that they were due to monosynaptic action of the I-wave. The results
      are consistent with cortico-motoneuronal (CM) connections originating from both
      SMA and M1 converging upon single motoneurons, but those from M1 are far more
      numerous and exert stronger excitatory effects than from the SMA. Thus although
      they may function in parallel, the two CM projections probably make different
      contributions to upper limb motor control.

PMID- 11839603
TI  - Brain mechanisms for reading words and pseudowords: an integrated approach.
AB  - The present study tested two predictions of dual-process models of reading: (i)
      that the brain structures involved in sublexical phonological analysis and those
      involved in whole-word phonological access during reading are different; and (ii)
      that reading of meaningful items, by means of the addressed phonology process, is
      mediated by different brain structures than reading of meaningless letter
      strings. We obtained brain activation profiles using Magnetic Source Imaging and,
      in addition, pronunciation latencies during reading of: (i) exception words
      (primarily involving addressed phonology and having meaning), (ii)
      pseudohomophones (requiring assembled phonology and having meaning), and (iii)
      pseudowords (requiring assembled phonology but having no meaning). Reading of
      meaningful items entailed a high degree of activation of the left posterior
      middle temporal gyrus (MTGp) and mesial temporal lobe areas, whereas reading the
      meaningless pseudowords was associated with much reduced activation of these two
      regions. Reading of all three types of print resulted in activation of the
      posterior superior temporal gyrus (STGp), inferior parietal and basal temporal
      areas. In addition, pronunciation speed of exception words correlated
      significantly with the onset of activity in MTGp but not STGp, whereas the
      opposite was true for pseudohomophones and pseudowords. These findings are
      consistent with the existence of two different brain mechanisms that support
      phonological processing in word reading: one mechanism that subserves assembled
      phonology and depends on the posterior part of STGp, and a second mechanism that
      is responsible for pronouncing words with rare print-to-sound correspondences and
      does not necessarily involve this region but instead appears to depend on MTGp.

PMID- 11839604
TI  - Serial memory strategies in macaque monkeys: behavioral and theoretical aspects.
AB  - Serial memory is the ability to encode and retrieve a list of items in their
      correct temporal order. To study nonverbal strategies involved in serial memory,
      we trained four macaque monkeys on a novel delayed sequence-recall task and
      analysed the mechanisms underlying their performance in terms of a neural network
      model. Thirty fractal images, divided into 10 triplets, were presented repeatedly
      in fixed temporal order. On each trial the monkeys viewed three sequentially
      presented sample images, followed by a test stimulus consisting of the same
      triplet of images and a distractor image (chosen randomly from the remaining 27).
      The task was to touch the three images in their original order, avoiding the
      distractor. The monkeys' most common error was touching the distractor when it
      had the same ordinal position (in its own triplet) as the correct image. This
      finding suggests that monkeys naturally categorize images by their ordinal
      number. Additional, secondary strategies were eventually used to avoid distractor
      images. These include memory of the sample images (working memory) and
      associations between triplet members. Further direct evidence for ordinal number
      categorization was provided by a transfer of learning to untrained images of the
      same ordinal category, following reassignment of image categories within each
      triplet. We propose a generic three-tier neuronal framework that can explain the
      components and complex set of characteristics of the observed behavior. This
      framework, with its intermediate level representing ordinal categories, can also
      explain the transfer of learning following category reassignment.

PMID- 11839605
TI  - Top-down controlled visual dimension weighting: an event-related fMRI study.
AB  - Target detection in visual singleton feature search is slowed when consecutive
      targets are defined in different visual dimensions. Behavioral data provide
      evidence that attentional weight needs to be shifted between dimension-specific
      processing modules. We found similar dimension-specific change effects in a
      conjunction search task, in which observers searched for an odd-one-out target
      defined by a unique combination of size and color or, respectively, size and
      motion direction. Changes of the secondary target dimension (color or motion)
      across trials, but not target feature changes within a dimension, increased the
      time required to detect the target. Dimensional change costs were greatly
      increased for singleton conjunction search compared to singleton feature search.
      This suggests involvement of top-down control processes in dimensional change in
      conjunction search, in contrast to stimulus-driven dimensional change in
      singleton feature search. The functional anatomical correlates of top-down
      controlled visual dimension changes were investigated in two event-related
      functional magnetic resonance imaging (fMRI) experiments. In Experiment 1,
      dimensional change in singleton conjunction search was accompanied by transient
      activations in a fronto-posterior network of brain areas that was largely non
      overlapping with the general network activated during visual search. Experiment
      2, which contrasted singleton feature and conjunction search within the same
      session, revealed a double dissociation in anterior prefrontal cortex: left
      frontopolar cortex was selectively involved in stimulus-driven dimension changes
      but not in top-down controlled dimension changes, whereas the reverse was
      observed in frontomedian cortex.

PMID- 11839607
TI  - A model for odour thresholds.
AB  - Odour detection thresholds, that we have previously obtained, have been analysed
      by a general equation for selective transport. It is shown that such selective
      transport can account for some 77% of the total effect. The remainder is due to a
      specific size effect, that might involve odour-binding proteins, and a specific
      effect for aldehydes and carboxylic acids. Our analysis raises the question of
      whether selective transport is physically separable from the specific effects of
      receptor activation. The model predicts a chemical cut-off in odour detection
      along any homologous series.

PMID- 11839606
TI  - Aging causes a preferential loss of cholinergic innervation of characterized
      neocortical pyramidal neurons.
AB  - Aging is known to markedly affect the number and structural characteristics of
      both pre- and post-synaptic sites in the cerebral cortex. There is evidence that
      lamina V pyramidal neurons, and their basilar dendrites in particular, are
      affected by age-related decline. Furthermore, layer V is the area where the
      greatest overall age- related losses in the total population of synaptic boutons
      and of cholinergic boutons are observed. Since both pyramidal neurons and
      cortical cholinergic input are characteristically compromised in aging, we
      investigated whether aging altered the pattern of cholinergic boutons in
      apposition to the soma, proximal and distal basal dendrites of intracellularly
      labeled lamina V large pyramidal neurons in the parietal cortex of young and aged
      rats. We observed a significant age-related decrease in the population of both
      total and cholinergic boutons apposed to proximal and distal dendrites of layer V
      large pyramidal neurons. However, the age-related decreases of cholinergic
      presynaptic boutons were higher than those in the total bouton population apposed
      to the pyramidal neurons. The average decrease in cholinergic boutons in aged
      rats was 3.7-fold more pronounced than the diminution in the overall number of
      presynaptic boutons. Our results add important new evidence in support of the
      concept that the age-related learning and memory deficits are attributable, at
      least partially, to a decline in the functional integrity of the forebrain
      cholinergic systems.

PMID- 11839608
TI  - A new specific ageusia: some humans cannot taste L-glutamate.
AB  - A new specific ageusia was found in human subjects for monosodium L-glutamate
      (MSG). Four tests were successively applied to discriminate non-tasters and
      hypotasters from tasters. (i) NaCl and MSG thresholds, and (ii) suprathreshold
      sensitivity were evaluated using the up-and-down procedure. Only 73% of 109
      subjects common to both tests demonstrated a sensitivity for MSG significantly
      higher than their sensitivity to NaCl, and hence a specific sensitivity to L
      glutamate. The remaining 27% who showed no significant difference in sensitivity
      to MSG and NaCl solutions were considered as putative hypotasters. (iii)
      Perception profiles (time-intensity) for MSG and NaCl were tested in 58 subjects
      and appeared significantly different in 47 tasters (81%). This technique helped
      in identifying among putative hypotasters of tests 1 and 2 a few tasters who
      perceived equal intensity for isoconcentration of NaCl and MSG but who could
      discriminate isomolar solutions on other cues. Thus, 19% of subjects, for whom no
      significant differences were found between MSG and NaCl time-intensity profiles,
      remained in the hypotaster group. (iv) A discrimination task including 24
      triangular presentations per subject of NaCl and MSG 29 mM applied to the eight
      most severe hypotasters showed that two subjects at least (two of 58; 3.5%) could
      not discriminate between both stimuli. Moreover, these subjects probably
      perceived identical sensations for MSG and NaCl solutions. The six other
      hypotasters (10.3%) could discriminate both stimuli at the limit of significance.
      None of these eight subjects were able to identify the typical umami taste in 29
      mM MSG.

PMID- 11839609
TI  - Olfactory acuity after total laryngectomy.
AB  - The olfactory acuity of 29 patients receiving laryngectomy was prospectively
      studied. The olfactory acuity was evaluated by Jet Stream Olfactometer (JSO) and
      Alinamin test preoperatively and at 3, 6 and 12 months postoperatively. The
      findings of nasal/olfactory mucosae were also observed by rigid endoscope. Based
      on the results of JSO, the averages of detection/recognition thresholds tended to
      increase 3 months postoperatively, then the averaged thresholds tended to
      decrease thereafter. There were significant differences between preoperative
      values and those 3 months after surgery, but there were no significant
      differences between preoperative values and these 6/12 months after surgery.
      Nasal respiratory mucosae observed 12 months after laryngectomy showed atrophic
      nasal mucosa in 11/14 patients. However, olfactory mucosae appeared normal in all
      of the patients observed. These results suggested that the function of the
      olfactory epithelium remained intact after laryngectomy.

PMID- 11839610
TI  - Cross-adaptation and bitterness inhibition of L-tryptophan, L-phenylalanine and
      urea: further support for shared peripheral physiology.
AB  - A previous study investigating individuals' bitterness sensitivities found a
      close association among three compounds: L-tryptophan (L-trp), L-phenylalanine (L
      phe) and urea (Delwiche et al., 2001, Percept. Psychophys. 63, 761-776). In the
      present experiment, psychophysical cross-adaptation and bitterness inhibition
      experiments were performed on these three compounds to determine whether the
      bitterness could be differentially affected by either technique. If the two
      experimental approaches failed to differentiate L-trp, L-phe and urea's
      bitterness, then we may infer they share peripheral physiological mechanisms
      involved in bitter taste. All compounds were intensity matched in each of 13
      subjects, so the judgments of adaptation or bitterness inhibition would be based
      on equal initial magnitudes and, therefore, directly comparable. In the first
      experiment, cross-adaptation of bitterness between the amino acids was high
      (>80%) and reciprocal. Urea and quinine-HCl (control) did not cross-adapt with
      the amino acids symmetrically. In a second experiment, the sodium salts, NaCl and
      Na gluconate, did not differentially inhibit the bitterness of L-trp, L-phe and
      urea, but the control compound, MgSO(4), was differentially affected. The bitter
      inhibition experiment supports the hypothesis that L-trp, L-phe and urea share
      peripheral bitter taste mechanisms, while the adaptation experiment revealed
      subtle differences between urea and the amino acids indicating that urea and the
      amino acids activate only partially overlapping bitter taste mechanisms.

PMID- 11839611
TI  - A brief-access test for bitter taste in mice.
AB  - Inbred mouse strains vary in their response to bitter-tasting compounds as
      assessed by 48 h preference tests. These differences are generally assumed to
      result from altered gustatory function, although such long-term tests could
      easily reflect additional factors. We developed a brief-access taste test and
      tested the responses of two inbred strains, as well as C3. SW congenic mice, to
      the bitter stimulus sucrose octaacetate (SOA). Water-deprived trained mice were
      tested with five concentrations of SOA (0.00018-0.18 mM) and distilled water in a
      Davis MS- 160 apparatus. Trials were 5 s in duration and stimuli were presented
      randomly within blocks; each stimulus trial was preceded by a water rinse trial.
      Each concentration was presented twice in a session and mice were repeatedly
      tested across consecutive days. SOA-taster mice, including the SWR/J (SW) inbred
      and C3. SW congenic taster (T) mice, avoided licking SOA at concentrations >0.003
      mM. In comparison, C3HeB/FeJ (C3) and C3. SW demitaster mice (D) licked all
      concentrations at the same rate as water. Concentration-response functions were
      similar across strains for both the brief-access test and a parallel 48 h
      preference test run on separate groups of mice. Furthermore, concentration
      response functions were similar whether or not the brief-access test was preceded
      by a 4 day, single concentration pretest with SOA. The brief-access test is a
      suitable assay for bitter taste function in mice because it minimizes possible
      post-ingestive influences on taste.

PMID- 11839612
TI  - Receptor neuron discrimination of the germacrene D enantiomers in the moth
      Helicoverpa armigera.
AB  - Plants release complex mixtures of volatiles, including chiral constituents. In
      the search for the biologically relevant plant odorants, gas chromatography
      linked to electrophysiological recordings from single receptor neurons has been
      employed. In heliothine moths, including the females of the Eurasian cotton
      bollworm moth Helicoverpa armigera, a major type of receptor neurons is
      identified, showing high sensitivity and selectivity for the sesquiterpene
      germacrene D. In the present study, gas chromatography with a chiral column
      linked to single cell recordings were performed. It was found that all germacrene
      D neurons belonged to one type; all responded to both enantiomers, but (-)
      germacrene D had approximately 10 times stronger effect than (+)-germacrene D.
      Parallel dose-response curves for the two enantiomers were obtained by direct
      stimulations. The enantiomeric composition of germacrene D, which differed in six
      plant species and in different individuals of one species, was determined on the
      basis of the neuron responses. The results, showing the presence of one neuron
      type for receiving the information about germacrene D in the various plants,
      suggests that the two enantiomers mediate the same kind of information to the
      moth, but with different intensity.

PMID- 11839613
TI  - Parabrachial unit activities after the acquisition of conditioned taste aversion
      to a non-preferred HCl solution in rats.
AB  - Abstract In a behavioral experiment, rats reliably acquired a taste aversion to
      non-preferred 0.01 M HCl that had been previously paired with intraperitoneal
      injection of 0.15 M LiCl. These rats showed aversions to other acidic solutions
      such as malic acid and tartaric acid. In a neurophysiological experiment, the
      neuronal activities of the parabrachial nucleus (PBN) were recorded after the
      acquisition of conditioned taste aversion (CTA) to 0.01 M HCl in urethane
      anesthetized rats. Neuronal responses to the conditioned stimulus (CS) did not
      change on the whole but decreased in the dorsal region to the brachium
      conjunctivum. The proportion of HCl-best to NaCl-best units was lower in the CTA
      group than in controls. The spontaneous firing rate was lower in the CTA group
      than in controls. Correlation coefficients between the HCl CS and normally
      preferred tastes (sucrose and NaCl) were more negative and those between HCl and
      quinine were more positive in the CTA group than in the controls. These results
      may be explained by the notion that gustatory responses of PBN neurons are
      concerned with alterations in taste hedonics after the acquisition of conditioned
      taste aversions.

PMID- 11839616
TI  - Conservative management of acute coronary syndrome: cheaper and better for you?

PMID- 11839617
TI  - Trans-fatty acids and sudden cardiac death.

PMID- 11839618
TI  - Stem cells combined with gene transfer for therapeutic vasculogenesis: magic
      bullets?

PMID- 11839619
TI  - Early afterdepolarizations, U waves, and torsades de pointes.

PMID- 11839620
TI  - Calcineurin inhibition attenuates mineralocorticoid-induced cardiac hypertrophy.
AB  - BACKGROUND: It remains unclear how mineralocorticoids induce cardiac hypertrophy
      and fibrosis. Recently, activation of the calcium-dependent phosphatase,
      calcineurin, has been shown to induce cardiac hypertrophy. In the present study,
      we examine the role of calcineurin in mineralocorticoid-induced cardiac
      hypertrophy and fibrosis. METHODS AND RESULTS: Uninephrectomized Wistar-Kyoto
      rats were placed on a 1.0% NaCl diet and treated with aldosterone (0.75 microg x
      h(-1)) for 6 weeks with or without the calcineurin inhibitors, FK506 (0.5 mg x
      kg(-1) x d(-1)) or cyclosporine A (10 mg x kg(-1) x d(-1)). The effect of the
      angiotensin II type 1 receptor antagonist, losartan (10 mg x kg(-1) x d(-1))on
      aldosterone-induced cardiac hypertrophy was also studied. Treatment with
      aldosterone increased the heart weight/body weight ratio, cardiomyocyte size, and
      collagen amount. The expression of mRNA of both type-III collagen and atrial
      natriuretic peptide in the heart were increased by aldosterone administration.
      Both calcineurin activity and its mRNA expression were also increased in
      aldosterone-induced hypertrophic heart. Treatment with losartan, FK506, or
      cyclosporine partially prevented aldosterone-induced cardiac hypertrophy and
      fibrosis. CONCLUSION: These results suggest that calcineurin is involved in the
      development of cardiac hypertrophy and fibrosis induced by mineralocorticoid
      excess. Inhibition of calcineurin may therefore prevent cardiac hypertrophy and
      fibrosis in mineralocorticoid hypertension.

PMID- 11839621
TI  - Cost-effectiveness of a conservative, ischemia-guided management strategy after
      non-Q-wave myocardial infarction: results of a randomized trial.
AB  - BACKGROUND: Use of coronary angiography after myocardial infarction has been
      controversial, with some physicians advocating routine use and others advocating
      selective use only after documentation of residual myocardial ischemia. The
      effects of these strategies on economic outcomes have not been established.
      METHODS AND RESULTS: We analyzed data from a randomized, controlled clinical
      trial conducted in 17 Department of Veterans Affairs hospitals that enrolled 876
      clinically uncomplicated patients 24 to 72 hours after an acute non-Q-wave
      myocardial infarction. The routine invasive strategy included early coronary
      angiography with revascularization based on established guidelines. The
      conservative, ischemia-guided strategy included noninvasive testing with
      radionuclide ventriculography and exercise thallium scintigraphy, followed by
      coronary angiography in patients with objective evidence of myocardial ischemia.
      We measured the cost of hospitalization and outpatient visits and tests during
      follow-up and calculated the incremental cost-effectiveness ratio. The
      conservative, ischemia-guided strategy had lower costs than the routine invasive
      strategy, both during the initial hospitalization ($14 733 versus $19 256,
      P<0.001) and after a mean follow-up of 1.9 years ($39 707 versus $41 893,
      P=0.04). The hazard ratio for death was 0.72 (confidence limits, 0.51 to 1.01) in
      the conservative strategy. The conservative strategy had lower costs and better
      outcomes in 76% of 1000 bootstrap replications, and a cost-effectiveness ratio
      below $50 000 per year of life added in 96% of replications. CONCLUSIONS: A
      conservative, ischemia-guided strategy of selective coronary angiography and
      revascularization for patients who develop objective evidence of recurrent
      ischemia is more cost-effective than a strategy of routine coronary angiography
      after uncomplicated non-Q-wave myocardial infarction.

PMID- 11839622
TI  - Inflammatory response after open heart surgery: release of heat-shock protein 70
      and signaling through toll-like receptor-4.
AB  - BACKGROUND: Coronary artery bypass grafting with the use of cardiopulmonary
      bypass is known to mediate an inflammatory response. The stress-inducible heat
      shock protein (HSP) 70 has been detected in myocardial cells after CABG, and toll
      like receptors (TLRs) are suggested as putative signaling receptors for the HSPs,
      mediating synthesis of inflammatory cytokines. The main aims of our study were to
      explore the release of HSP70 and the regulation of monocyte TLR-2 and TLR-4
      expression after CABG. METHODS AND RESULTS: Twenty patients referred for elective
      CABG were included in this study. Using immunoassays, we detected HSP70 in plasma
      after CABG, with peak concentration immediately after surgery. Interleukin-6 in
      plasma reached peak concentration 5 hours after surgery. Monocyte CD14, TLR-2,
      and TLR-4 expression, as analyzed by flow cytometry, was initially downregulated.
      On day 1, CD14 expression normalized, whereas TLR-2 and TLR-4 expression was
      upregulated. TLR-4 was significantly upregulated even on postoperative day 2.
      Additional experiments revealed that peritoneal macrophages from control
      (C3H/HeN) mice responded to HSP70 with release of tumor necrosis factor, whereas
      macrophages from mutated TLR-4 (C3H/HeJ) mice were unresponsive. In vitro, human
      adherent monocytes responded to recombinant HSP70 with interleukin-6 and tumor
      necrosis factor release. CD14 and TLR-4 monoclonal antibodies inhibited the
      cytokine response. CONCLUSIONS: In this study, we observed an immediate release
      of HSP70 into the circulation and a modulation of monocyte TLR-2 and TLR-4
      expression after CABG. TLR-4 and CD14 appear to be involved in an HSP70-mediated
      activation of innate immunity.

PMID- 11839623
TI  - Early and sustained survival benefit associated with statin therapy at the time
      of percutaneous coronary intervention.
AB  - BACKGROUND: Long-term administration of statin therapy has been shown to reduce
      major coronary events and cardiac mortality within randomized clinical trials. In
      addition to lowering lipids, statins favorably affect platelet adhesion,
      thrombosis, endothelial function, inflammation, and plaque stability, which may
      potentially improve outcome after percutaneous coronary intervention (PCI).
      Therefore, we hypothesized that statin therapy has an early beneficial effect
      among patients undergoing PCI. METHODS AND RESULTS: Each year from 1993 to 1999,
      we prospectively collected data among the first 1000 patients undergoing PCI.
      Patients who presented with acute or recent myocardial infarction or cardiogenic
      shock were excluded from the analysis. Baseline, procedural, and 6-month data of
      statin-treated and non-statin-treated patients were compared. Propensity score
      and multivariate survival analysis were used to adjust for heterogeneity between
      the two groups. Of 5052 patients who completed follow-up, 26.5% were treated with
      statin at the time of the procedure. Statin therapy was associated with a
      mortality reduction at 30 days (0.8% versus 1.5%; hazard ratio, 0.53; P=0.048)
      and at 6 months (2.4% versus 3.6%; hazard ratio, 0.67; P=0.046). After adjusting
      for the propensity to receive statin therapy before the procedure and other
      confounders, statin therapy remained an independent predictor for survival at 6
      months after coronary intervention (hazard ratio, 0.65; 95% CI, 0.42 to 0.99;
      P=0.045). CONCLUSIONS: In this large study cohort, statin therapy among PCI
      patients seems to be associated with a significant mortality advantage at early
      and intermediate-term follow-up.

PMID- 11839624
TI  - Cell membrane trans-fatty acids and the risk of primary cardiac arrest.
AB  - BACKGROUND: The relation of trans-fatty acid intake to life-threatening
      arrhythmias and primary cardiac arrest is unknown. METHODS AND RESULTS: We
      investigated the association of trans-fatty acid intake, assessed through a
      biomarker, with the risk of primary cardiac arrest in a population-based case
      control study. Cases, aged 25 to 74 years, were out-of-hospital cardiac arrest
      patients attended by paramedics in Seattle, Washington from 1988 to 1999 (n=179).
      Controls, matched to cases by age and sex, were randomly identified from the
      community (n=285). Participants were free of previous clinically diagnosed heart
      disease. Blood was obtained at the time of cardiac arrest (cases) or at the time
      of an interview (controls) to assess trans-fatty acid intake. Higher total trans
      fatty acids in red blood cell membranes was associated with a modest increase in
      the risk of primary cardiac arrest after adjustment for medical and lifestyle
      risk factors (odds ratio for interquintile range, 1.5; 95% CI, 1.0 to 2.1).
      However, trans isomers of oleic acid were not associated with risk (odds ratio
      for interquintile range, 0.8; 95% CI, 0.5 to 1.2), whereas higher levels of trans
      isomers of linoleic acid were associated with 3-fold increase in risk (odds ratio
      for interquintile range, 3.1; 95% CI, 1.7 to 5.4). CONCLUSIONS: These findings
      suggest that dietary intake of total trans-fatty acids is associated with modest
      increase and trans isomers of linoleic acid with a larger increase in the risk of
      primary cardiac arrest. These associations need to be confirmed in future studies
      that distinguish between trans isomers of linoleic acid and trans isomers of
      oleic acid.

PMID- 11839625
TI  - Cardiac autonomic dysfunction in Brugada syndrome.
AB  - BACKGROUND: Patients with Brugada syndrome present with characteristic ECG
      abnormalities (atypical right bundle-branch block and ST-segment elevation) and
      life-threatening ventricular tachyarrhythmias despite structurally normal hearts.
      Involvement of the autonomic nervous system is suggested by the occurrence of
      ventricular tachyarrhythmias and sudden death at rest or during sleep and by
      changes of typical ECG signs under pharmacological modulation of the myocardial
      autonomic tone. METHODS AND RESULTS: This study investigated the presynaptic
      cardiac neuronal reuptake of norepinephrine (uptake 1) in 17 patients with
      Brugada syndrome and 10 age-matched control subjects with the use of the
      norepinephrine analogue [123I]m-iodobenzylguanidine (123I-MIBG), single-photon
      emission CT (SPECT), and quantitative 33-segment bull's-eye analysis. Regionally
      reduced 123I-MIBG uptake was present in 8 (47%) of 17 patients with Brugada
      syndrome but in none of the control subjects. Quantitative analysis showed
      segmental reduction of 123I-MIBG uptake in the inferior and septal left
      ventricular wall in patients with Brugada syndrome compared with control subjects
      (P<0.05). No correlation was found between the findings of 123I-MIBG-SPECT and
      clinical characteristics of the study patients. CONCLUSIONS: The present study
      demonstrated an abnormal 123I-MIBG uptake in patients with Brugada syndrome,
      indicating presynaptic sympathetic dysfunction of the heart. These findings may
      have potential impact on the pathophysiology and arrhythmogenesis in patients
      with Brugada syndrome. Future quantitative investigations of the presynaptic and
      postsynaptic sympathetic and parasympathetic branches of the cardiac autonomic
      nervous system may clarify whether these observations represent a primary
      adrenergic dysfunction or an imbalance between sympathetic and parasympathetic
      innervation of the heart.

PMID- 11839626
TI  - Clinical and molecular heterogeneity in the Brugada syndrome: a novel gene locus
      on chromosome 3.
AB  - BACKGROUND: Brugada syndrome is a form of idiopathic ventricular fibrillation
      characterized by a right bundle-branch block pattern and ST elevation (STE) in
      the right precordial leads of the ECG. Sodium channel blockers increase STE.
      Mutations of the cardiac sodium channel SCN5A cause the disorder, and an
      implantable cardioverter-defibrillator is often recommended for affected
      individuals. Mutations in other genes have not been identified, and it is not
      known if the efficacy of drug testing or the malignancy of arrhythmias correlates
      to the gene defect. METHODS AND RESULTS: We performed histories, physical
      examinations, ECGs, and drug testing on a large multigenerational family with
      Brugada syndrome. DNA isolated from blood samples, polymorphic genomic markers,
      and polymorphisms within candidate sodium channels were used for a genome-wide
      screen, fine mapping, and linkage analysis. We identified 12 affected individuals
      (right bundle-branch block, > or =1-mm STE) with an autosomal dominant
      inheritance pattern characterized by incomplete penetrance that appeared to be
      dependent on age and sex. Four affected individuals had syncope and 2 had
      documented ventricular arrhythmias, but there was minimal family history of
      sudden death. Procainamide infusions did not identify additional affected
      individuals. Linkage was present to an approximately equal 15-cM region on
      chromosome 3p22-25 (maximum LOD score=4.00). The sodium channel genes SCN5A,
      SCN10A, and SCN12A on chromosome 3 were excluded as candidates (LOD scores < or =
      2). CONCLUSIONS: A Brugada syndrome locus distinct from SCN5A is associated with
      progressive conduction disease, a low sensitivity to procainamide testing, and a
      relatively good prognosis in a single large pedigree.

PMID- 11839627
TI  - Principal component analysis of the T wave and prediction of cardiovascular
      mortality in American Indians: the Strong Heart Study.
AB  - BACKGROUND: Increased QT interval dispersion (QTd) is a proposed ECG marker of
      vulnerability to ventricular arrhythmias and of cardiovascular (CV) mortality.
      However, principal component analysis (PCA) of the T-wave vector loop may more
      accurately represent repolarization abnormalities than QTd. METHODS AND RESULTS:
      Predictive values of QTd and PCA were assessed in 1839 American Indian
      participants in the first Strong Heart Study examination. T-wave loop morphology
      was quantified by the ratio of the second to first eigenvalues of the T-wave
      vector by PCA (PCA ratio); QTd was quantified as the difference between maximum
      and minimum QT intervals. After 3.7+/-0.9 years mean follow-up, there were 55 CV
      deaths. In univariate analyses, an increased PCA ratio predicted CV mortality in
      women (chi2=7.8, P=0.0053) and men (chi2=9.5, P=0.0021). In contrast, increased
      QTd was a significant predictor of CV mortality in women (chi2=30.6, P<0.0001)
      but not in men (chi2=2.0, P=NS). In multivariate Cox analyses controlling for
      risk factors and rate-corrected QT interval, the PCA ratio remained a significant
      predictor of CV mortality in women (chi2=4.0 P=0.043) and men (chi2=6.4,
      P=0.011); QTd was a significant predictor in women only (chi2=11.0, P=0.0009).
      PCA ratios >90th percentile (32% in women and 24.6% in men) identified women with
      a 3.68-fold increased risk of CV mortality (95% CI, 1.54 to 8.83) and men with a
      2.77-fold increased risk (95% CI, 1.18 to 6.49). CONCLUSIONS: Abnormalities of
      repolarization measured by PCA of the T-wave loop predict CV death in men and
      women, supporting use of PCA for quantifying repolarization abnormalities.

PMID- 11839628
TI  - Altered expression of ADAMs (A Disintegrin And Metalloproteinase) in fibrillating
      human atria.
AB  - BACKGROUND: ADAMs (A Disintegrin And Metalloproteinase) are ectoproteases that
      have recently been reported to be expressed in cardiac tissue. Although they are
      known to regulate cell-cell and cell-matrix interactions, their
      pathophysiological role in various cardiac diseases is unclear. The purpose of
      the present study was to determine whether structural remodeling of the atria
      during atrial fibrillation (AF) is associated with altered ADAM expression.
      METHODS AND RESULTS: Atrial tissue samples of 30 patients undergoing open-heart
      surgery were examined. Fifteen patients had persistent AF (> or =6 months), and
      the remaining 15 patients had no history of AF. ADAM9, ADAM10, and ADAM15
      expression was analyzed quantitatively at the mRNA and protein levels. ADAM
      expression was localized by immunohistochemistry. ADAM expression was correlated
      with amounts of integrins beta1 and beta3. The amount of ADAM10 protein more than
      doubled during AF (82+/-15 versus 36+/-8 U; P<0.01). Amounts of ADAM15 protein
      (102+/-12 versus 40+/-6 U; P<0.01) and mRNA (24.0+/-5.6 versus 10.5+/-2.5 U;
      P<0.05) increased significantly during AF compared with sinus rhythm. ADAM9
      protein was not detected in any sample. ADAM/integrin ratios showed an increase
      of 4- to 6-fold (P<0.05) in patients with AF who had significantly dilated atria
      (4.94+/-0.6 versus 4.3+/-0.7 cm; P<0.05). ADAM/integrin ratios correlated with
      atrial diameter. CONCLUSIONS: AF is associated with an increase in the expression
      of ADAM10 and ADAM15. Enhanced ADAM-dependent disintegrin and metalloproteinase
      activity may be a molecular mechanism that contributes to the dilation of
      fibrillating human atria.

PMID- 11839629
TI  - Isthmus characteristics of reentrant ventricular tachycardia after myocardial
      infarction.
AB  - BACKGROUND: The reentrant mechanism of postinfarct ventricular tachycardia (VT)
      has been documented by surgical mapping analysis, but little is known about
      postinfarct VT circuits and the characteristics of their related protected
      isthmus with the use of 3D catheter mapping systems. METHODS AND RESULTS: A 3D
      electroanatomic mapping was performed in 21 patients with well-tolerated,
      postinfarct, sustained VT. In total, 33 episodes of tachycardia (mean cycle
      length 432+/-74 ms) were induced and mapped. Complete maps demonstrated
      macroreentrant circuits with 1 loop (n=8) or 2 loops (n=25) rotating around a
      protected isthmus bounded by 2 approximately parallel conduction barriers that
      consisted of a line of double potentials, a scar area, or the mitral annulus. A
      total of 26 critical isthmi were identified for the 33 VTs mapped, with the same
      isthmus being shared by 2 to 4 different tachycardic morphologies in 5 patients.
      On average, isthmi were 31+/-7 mm long (ranging from 18 to 41 mm) and 16+/-8 mm
      wide (ranging from 6 to 36 mm) and harbored diastolic electrograms. The isthmus
      axis was oriented parallel to the mitral annulus plane in perimitral circuits and
      perpendicular to the mitral annulus plane in all other circuits. Linear
      radiofrequency ablation performed across the most accessible part of the isthmus
      prevented the recurrence of tachycardia in 19 patients (90%) with a follow-up at
      16+/-8 months. CONCLUSIONS: Detailed 3D electroanatomic mapping is helpful in
      reconstructing postinfarct VT circuits and in defining the characteristics of
      their related protected isthmi. The wide range of isthmus width values supports
      the need of linear radiofrequency lesions to eliminate the reentrant substrate of
      postinfarct VTs.

PMID- 11839630
TI  - Endothelial progenitor cell vascular endothelial growth factor gene transfer for
      vascular regeneration.
AB  - BACKGROUND: Previous studies have established that bone marrow-derived
      endothelial progenitor cells (EPCs) are present in the systemic circulation. In
      the current study, we investigated the hypothesis that gene transfer can be used
      to achieve phenotypic modulation of EPCs. METHODS AND RESULTS: In vitro, ex vivo
      murine vascular endothelial growth factor (VEGF) 164 gene transfer augmented EPC
      proliferative activity and enhanced adhesion and incorporation of EPCs into
      quiescent as well as activated endothelial cell monolayers. To determine if such
      phenotypic modulation may facilitate therapeutic neovascularization, heterologous
      EPCs transduced with adenovirus encoding VEGF were administered to athymic nude
      mice with hindlimb ischemia; neovascularization and blood flow recovery were both
      improved, and limb necrosis/autoamputation were reduced by 63.7% in comparison
      with control animals. The dose of EPCs used for the in vivo experiments was 30
      times less than that required in previous trials of EPC transplantation to
      improve ischemic limb salvage. Necropsy analysis of animals that received DiI
      labeled VEGF-transduced EPCs confirmed that enhanced EPC incorporation
      demonstrated in vitro contributed to in vivo neovascularization as well.
      CONCLUSIONS: In vitro, VEGF EPC gene transfer enhances EPC proliferation,
      adhesion, and incorporation into endothelial cell monolayers. In vivo, gene
      modified EPCs facilitate the strategy of cell transplantation to augment
      naturally impaired neovascularization in an animal model of experimentally
      induced limb ischemia.

PMID- 11839632
TI  - In vitro susceptibility to thrombin-induced platelet microbicidal protein is
      associated with reduced disease progression and complication rates in
      experimental Staphylococcus aureus endocarditis: microbiological,
      histopathologic, and echocardiographic analyses.
AB  - BACKGROUND: Mammalian platelets contain small, cationic, staphylocidal peptides,
      termed thrombin-induced platelet-microbicidal proteins (tPMPs). Evidence suggests
      that tPMPs play a key role in host defense against endovascular infections, such
      as infective endocarditis (IE). In the present study, we evaluated the influence
      of differences in staphylococcal tPMP-susceptibility profiles in vitro on disease
      severity in experimental IE. METHODS AND RESULTS: Experimental IE was induced in
      rabbits with either a tPMP-susceptible or an isogenic tPMP-resistant
      Staphylococcus aureus strain. Vegetation size, left ventricular fractional
      shortening, and onset of aortic valvular regurgitation were serially assessed by
      echocardiography over an 11-day postinfection period. In addition, blood cultures
      were performed daily. Parameters delineated at autopsy included vegetation
      weights; bacterial densities in vegetations, myocardium, and kidneys; extent of
      valvular and perivalvular tissue damage; and renal embolization. The following
      significant differences were observed in animals infected with the tPMP
      susceptible versus the tPMP-resistant S aureus strain: substantially lower
      bacteremia rates (P=0.02); reduced vegetation growth (P<0.001) and weight
      (P<0.001); a later onset of aortic valvular regurgitation (P=0.0039); increased
      preservation of left ventricular function (P<0.001); reduced valvular tissue
      damage (P=0.01) and perivalvular inflammation (P=0.015); and reduced bacterial
      densities in vegetations (P<0.001) and kidneys (P<0.01). CONCLUSIONS: The in
      vitro tPMP-susceptibility profile in S aureus substantially affects a number of
      well-defined cardiac and microbiological parameters related to disease severity
      and prognosis in IE. These findings underscore the likelihood that platelets
      mitigate the pathogenesis of endovascular infections via local secretion of
      antimicrobial peptides.

PMID- 11839631
TI  - Statins have biphasic effects on angiogenesis.
AB  - BACKGROUND: Statins inhibit HMG-CoA reductase to reduce the synthesis of
      cholesterol and isoprenoids that modulate diverse cell functions. We investigated
      the effect of the statins cerivastatin and atorvastatin on angiogenesis in vitro
      and in vivo. METHODS AND RESULTS: Endothelial cell proliferation, migration, and
      differentiation were enhanced at low concentrations (0.005 to 0.01 micromol/L)
      but significantly inhibited at high statin concentrations (0.05 to 1 micromol/L).
      Antiangiogenic effects at high concentrations were associated with decreased
      endothelial release of vascular endothelial growth factor and increased
      endothelial apoptosis and were reversed by geranylgeranyl pyrophosphate. In
      murine models, inflammation-induced angiogenesis was enhanced with low-dose
      statin therapy (0.5 mg x kg(-1) x d(-1)) but significantly inhibited with high
      concentrations of cerivastatin or atorvastatin (2.5 mg x kg(-1) x d(-1)). Despite
      the fact that high-dose statin treatment was effective at reducing lipid levels
      in hyperlipidemic apolipoprotein E-deficient mice, it impaired rather than
      enhanced angiogenesis. Finally, high-dose cerivastatin decreased tumor growth and
      tumor vascularization in a murine Lewis lung cancer model. CONCLUSIONS: HMG-CoA
      reductase inhibition has a biphasic dose-dependent effect on angiogenesis that is
      lipid independent and associated with alterations in endothelial apoptosis and
      vascular endothelial growth factor signaling. Statins have proangiogenic effects
      at low therapeutic concentrations but angiostatic effects at high concentrations
      that are reversed by geranylgeranyl pyrophosphate. At clinically relevant doses,
      statins may modulate angiogenesis in humans via effects on geranylated proteins.

PMID- 11839633
TI  - Selective matrix metalloproteinase inhibition reduces left ventricular remodeling
      but does not inhibit angiogenesis after myocardial infarction.
AB  - BACKGROUND: Broad inhibition of matrix metalloproteinases (MMPs) attenuates left
      ventricular remodeling after myocardial infarction (MI). However, it is not clear
      if selective MMP inhibition strategies will be effective or if MMP inhibition
      will impair angiogenesis after MI. METHODS AND RESULTS: We used a selective MMP
      inhibitor (MMPi) that does not inhibit MMP-1 in rabbits, which, like humans but
      unlike rodents, express MMP-1 as a major collagenase. On day 1 after MI, rabbits
      were randomized to receive either inhibitor (n=10) or vehicle (n=8). At 4 weeks
      after MI, there were no differences in infarct size or collagen fractional area.
      However, MMPi reduced ventricular dilation. The increase in end-diastolic
      dimension from day 1 to week 4 was 3.1+/-0.5 mm for vehicle versus 1.3+/-0.3 mm
      for MMPi (P<0.01). The increase in end-systolic dimension was 2.8+/-0.5 mm for
      vehicle and 1.3+/-0.4 mm for MMPi (P<0.05). Furthermore, MMPi reduced infarct
      wall thinning; the minimal infarct thickness was 0.8+/-0.1 mm for vehicle and
      1.6+/-0.3 mm for MMPi (P<0.05). Interestingly, the MMPi group had increased
      numbers of vessels in the subendocardial layer of the infarct; the number of
      capillaries was increased in the subendocardial layer (46+/-4 vessels/field
      versus 17+/-3 vessels/field for vehicle; P<0.001), and the number of arterioles
      was also increased (4.0+/-0.8 vessels/field versus 2.0+/-0.4 vessels/field for
      vehicle; P<0.05). CONCLUSIONS: MMP inhibition attenuates left ventricular
      remodeling even when the dominant collagenase MMP-1 is not inhibited;
      furthermore, this selective MMP inhibition appears to increase rather than
      decrease neovascularization in the subendocardium.

PMID- 11839635
TI  - Systemic production of vascular endothelial growth factor and fms-like tyrosine
      kinase-1 receptor in acute Kawasaki disease.
AB  - BACKGROUND: Increased vascular permeability is an important event during the
      initial process of Kawasaki disease (KD). One potential responsible candidate for
      the induction of vascular hyperpermeability is vascular endothelial growth factor
      (VEGF). METHODS AND RESULTS: We investigated the expression of VEGF and its
      receptors (flt-1, KDR) in acute KD tissues at 7 days to 5 weeks of illness.
      Neuropilin-1, which enhances the binding of VEGF(165) to KDR, was also studied.
      Abundant expression of VEGF and flt-1 was documented immunohistochemically in
      many organs from acute KD, including heart and lung. VEGF and flt-1 were
      colocalized in all vessels that showed edema. These molecules resided in
      endothelium and vascular media and also in migrating smooth muscle cells in
      neointima and infiltrating macrophages. Compared with controls, coronary vessels
      of acute KD had upregulation of VEGF and flt-1 but not KDR or neuropilin-1. KDR
      was expressed by vessels at 7 days of illness but not later in the illness.
      Plasma proteins were more extensively bound to the extracellular matrix in
      coronary vessels in acute KD than controls. Furthermore, elevation of serum VEGF
      levels was correlated with low serum albumin in acute KD (n=220, r=-0.53,
      P<0.001). CONCLUSIONS: These findings suggest that VEGF and flt-1 are upregulated
      in blood vessels in many organs of acute KD. Expression of KDR was limited to the
      early stage of acute KD. The roles of VEGF in acute KD may involve promotion of
      vascular permeability and macrophage activation. Low serum albumin may indicate
      overproduction of VEGF in acute KD.

PMID- 11839637
TI  - Steps toward percutaneous aortic valve replacement.
AB  - BACKGROUND: To date, the surgical approach is the only option to replace the
      aortic valve. Percutaneous pulmonary valve replacement has recently opened new
      perspectives on transcatheter replacement of cardiac valves. We report our
      experience of aortic valve replacement through a percutaneous technique in lambs.
      METHODS AND RESULTS: A bovine jugular vein containing a valve was dissected and
      sutured into a stent. Twelve lambs were divided into 3 groups. In the first, a
      valved stent was implanted in the descending aorta after creation of an aortic
      insufficiency. In the second, the valve was implanted in the native position. In
      the third, we inserted a valved stent in the native position using an orientation
      mechanism. All valves were successfully delivered and functioned perfectly in
      short-term evaluation. All experiments in group 2 failed: 1 valve obstructed the
      coronary artery orifices, 1 stent was responsible for a major mitral valve
      insufficiency, and the third implant migrated prematurely. A paraprosthetic leak
      occurred in the last animal in this group. Animals in group 3 had successful
      implantation of the valved stent. The orientation mechanism allowed perfect
      alignment of the device without any damage to the coronary circulation or to
      mitral valve function. CONCLUSIONS: Nonsurgical implantation of an aortic valve
      is possible in lambs in the descending aorta and in the native position. An
      orientation mechanism is obviously needed to avoid obstruction of the coronary
      orifices. With further improvements, this technique should be feasible in humans.

PMID- 11839634
TI  - Myocardial contrast echocardiography can be used to assess the microvascular
      response to vascular endothelial growth factor-121.
AB  - BACKGROUND: Therapeutic angiogenesis is a new approach to treating ischemic heart
      disease, and the optimal method for assessing its efficacy is unclear. We used
      myocardial contrast echocardiography (MCE) to evaluate the therapeutic response
      to the angiogenic agent, vascular endothelial growth factor-121 (VEGF121).
      METHODS AND RESULTS: After placement of an ameroid constrictor (day 0) around the
      left anterior descending artery (LAD), dogs were given intracoronary VEGF121
      protein (108 microg, n=6) or placebo (n=6) on days 7 and 21, and subcutaneous
      VEGF121 (1 mg) or placebo on days 8 to 20 and 22 to 27. On day 48, MCE was
      performed during rest and dobutamine stress. Videointensity (y) and pulsing
      interval (t) were fit to an exponential model (y=A[1-e(-beta(t))]) used to derive
      indices of red cell velocity (beta) and capillary area (A), and parameters were
      compared with radiolabeled microsphere flow data. VEGF(121) treatment resulted in
      higher resting left anterior descending artery/left circumflex flow ratio
      compared with placebo (P<0.03) and improved collateral flow reserve. Beta was
      0.94+/-0.37 in VEGF121 dogs versus 0.38+/-0.31 in controls (P<0.02), with the
      greatest difference in the endocardium. The parameter A was comparable in both
      groups, suggesting that microvascular changes did not alter capillary cross
      sectional area, and histology indicated a trend toward higher arteriolar density
      in VEGF121-treated animals. CONCLUSIONS: VEGF121 protein improves collateral flow
      and reserve. MCE can evaluate the transmural location and structural and
      functional responses of the microvasculature to angiogenic interventions.

PMID- 11839636
TI  - Calmodulin inhibitor W-7 unmasks a novel electrocardiographic parameter that
      predicts initiation of torsade de pointes.
AB  - BACKGROUND: We have shown that the calmodulin inhibitor W-7 suppresses torsade de
      pointes (TdP) without shortening the QT interval, which is consistent with other
      findings that QT prolongation, per se, is insufficient to generate TdP. ECGs were
      analyzed from a well-characterized animal model of TdP to identify more reliable
      predictors of this life-threatening ventricular arrhythmia. METHODS AND RESULTS:
      TdP was induced using methoxamine and clofilium in 12 of 14 rabbits pretreated
      with vehicle control, whereas pretreatment with W-7 (50 micromol/kg), an
      inhibitor of the intracellular Ca2+-binding protein calmodulin, significantly
      suppressed TdP induction (1 of 11 rabbits with TdP, P<0.001). W-7 did not affect
      heart rate, increases in QT intervals, or dispersion compared with measurements
      in vehicle-treated control animals. However, a progressive and significant
      increase in the ratio of U-wave to T-wave amplitude (UTA) occurred before TdP
      onset in control animals, and this was prevented by W-7. CONCLUSIONS: Selective
      suppression of TdP inducibility by W-7, without shortening the duration of
      cardiac repolarization, allowed identification of the UTA ratio as a new
      electrocardiographic index for predicting TdP onset. These findings are
      consistent with the idea that prolonged repolarization is not the proximate cause
      of arrhythmia initiation, and they suggest that an increased UTA ratio reflects
      activation of intracellular Ca2+/calmodulin-dependent processes that are required
      for triggering TdP in this model.

PMID- 11839638
TI  - Images in cardiovascular medicine. A broken heart.

PMID- 11839639
TI  - Images in cardiovascular medicine. Anomalous course of the left main or left
      anterior descending coronary artery originating from the right sinus of valsalva:
      identification of four common variations by electron beam tomography.

PMID- 11839640
TI  - Cardiac energetics in congestive heart failure.

PMID- 11839641
TI  - Eptifibatide and 7E3, but not tirofiban, inhibit alpha(v)beta3 integrin-mediated
      binding of smooth muscle cells to thrombospondin and prothrombin.

PMID- 11839642
TI  - Mechanisms of platypnea-orthodeoxia: what causes water to flow uphill?

PMID- 11839643
TI  - Heart failure with a normal ejection fraction.

PMID- 11839644
TI  - New roles for statins.

PMID- 11839645
TI  - Protein kinase A type I: a target for cancer therapy.

PMID- 11839646
TI  - Cancer prevention by delay. Commentary re: J. A. O'Shaughnessy et al., Treatment
      and Prevention of Intraepithelial Neoplasia: An Important Target for Accelerated
      New Agent Development. Clin. Cancer Res., 8: 314-346, 2002.

PMID- 11839647
TI  - Treatment and prevention of intraepithelial neoplasia: an important target for
      accelerated new agent development.
AB  - Precancer or intraepithelial neoplasia (IEN) is a noninvasive lesion that has
      genetic abnormalities, loss of cellular control functions, and some phenotypic
      characteristics of invasive cancer and that predicts for a substantial likelihood
      of developing invasive cancer. The AACR Task Force on the Treatment and
      Prevention of IEN has delineated the relationship between IEN and cancer risk as
      well as the clinical benefit that can be derived from reducing IEN burden.
      Although several effective endoscopic and surgical treatments for IEN have become
      standard medical practice, these interventions can confer morbidity and do not
      treat the entire epithelial field at risk. The incidence of many epithelial
      cancers is continuing to rise, the number of individuals at risk is increasing
      with the aging population, and the rapid advancement of imaging and molecular
      diagnostics is bringing to light precancers that were heretofore clinically
      silent. There is therefore an urgent need to rapidly develop new treatment and
      prevention agents for IEN. The AACR IEN Task Force recommends focusing on
      established precancers as the target for new agent development because of the
      close association between dysplasia and invasive cancer and because a convincing
      reduction in IEN burden provides patient benefit by reducing cancer risk and/or
      by decreasing the need for invasive interventions. The IEN Task Force proposes
      several clinical trial designs that provide practical and feasible approaches to
      the rapid development of new agents to treat and prevent precancer.

PMID- 11839648
TI  - NH(2)-terminal truncated HER-2 protein but not full-length receptor is associated
      with nodal metastasis in human breast cancer.
AB  - BACKGROUND: The full-length receptor p185HER-2 undergoes a metalloprotease
      dependent cleavage producing a membrane-associated fragment (p95HER-2) in
      cultured breast cancer cells. P95HER-2 has potentially enhanced signaling
      activity, but its expression and role in human breast cancer is poorly
      characterized. PURPOSE: The purpose of this project was to characterize the
      expression of p95HER-2 in primary breast cancers and nodal metastasis, and to
      study association with clinicopathological factors. EXPERIMENTAL DESIGN: P95HER-2
      and p185HER-2 were examined in 337 primary breast tumors and 81 metastatic lymph
      nodes by Western blot analysis, and tested for associations with other
      clinicopathological factors. RESULTS: P95HER-2 was present in 20.9% of primary
      tumors from node-negative patients, in 29.1% from patients with one to three
      metastatic nodes, and in 36.7% from patients with four or more metastatic nodes
      (P = 0.027). Whereas p185HER-2 overexpression was unrelated to nodal disease (P =
      0.63), the odds of lymph node metastasis were enhanced 2.9-fold by the presence
      of p95HER-2 (48.8% of node-negative versus 73.5% of node-positive patients; P =
      0.03; odds ratio = 2.9). P95HER-2 was more frequent in metastatic lymph nodes
      than in primary tumors (45.7% versus 26.7%; P = 0.0009), whereas p185HER-2
      overexpression was similar in both (22.3% versus 23.5%; P = 0.933). P95HER-2 did
      not significantly correlate with patient age, tumor size, stage, histotype, or
      hormone receptor status. CONCLUSIONS: P95HER-2 in primary tumors was related to
      extent of lymph node involvement and was enhanced in nodal tissue suggesting an
      important role as a marker or cause in breast cancer metastasis. Examination of
      the prognostic value of p95HER-2 in breast cancer and its coexpression with
      metalloprotease activity seem warranted.

PMID- 11839649
TI  - Sulindac enhances tumor necrosis factor-alpha-mediated apoptosis of lung cancer
      cell lines by inhibition of nuclear factor-kappaB.
AB  - Programmed cell death (apoptosis) is induced by certain anticancer therapies, and
      resistance to apoptosis is a major mechanism by which tumors evade these
      therapies. The transcription factor nuclear factor (NF)-kappaB, which is
      frequently activated by treatment of cancer cells with different chemotherapeutic
      agents, promotes cell survival, whereas its inhibition leads to enhanced
      apoptosis. Recently, sulindac and other nonsteroidal anti-inflammatory drugs have
      been shown to inhibit tumor necrosis factor (TNF)-alpha-mediated NF-kappaB
      activation. Here, we demonstrate that treatment of the non-small cell lung
      carcinoma cells NCI-H157 and NCI-H1299 with sulindac greatly enhances TNF-alpha
      mediated apoptosis. We further show that sulindac inhibits TNF-alpha-mediated
      activation of NF-kappaB DNA binding and nuclear translocation of NF-kappaB. These
      results suggest that sulindac and other nonsteroidal anti-inflammatory drug
      inhibitors of NF-kappaB activation may serve as useful agents in cancer
      chemotherapy.

PMID- 11839650
TI  - Expression profile of tyrosine kinases in breast cancer.
AB  - The tyrosine kinase (TK) family includes many growth factor receptors, cell cycle
      regulators, and oncoproteins. Moreover, the receptor TKs HER2/neu and epidermal
      growth factor receptor are overexpressed in a subgroup of breast tumors and
      correlate with more aggressive behavior. Thus, TKs are being actively pursued as
      therapeutic targets. The purpose of this study was to determine the expression
      pattern of TKs in breast cancer. Reverse transcription-PCR was performed with
      degenerate primers based on conserved motifs of the catalytic domains of TKs, and
      the identities of the reverse transcription-PCR products were determined by
      digestion with a panel of restriction enzymes. Using a TK display assay, we
      studied the TK profiles of 13 breast cancer cell lines and two normal
      immortalized breast epithelial cell lines. The TK display assay reproducibly
      demonstrated known differences in HER-2/neu expression between cell lines.
      Several TKs, including receptor TKs Axl, Cak, fibroblast growth factor receptor
      4, HEK8, HER2/neu, c-MET, RET, and nonreceptor TKs ARG, BRK, Janus kinase 1, Rak,
      and YES were detected in breast cancer cells. Several kinases were differentially
      expressed among the cell lines. Similar TK profiles were found using RNA from
      human breast tumors. We conclude that there is significant variability in the TK
      expression pattern of breast cancers. This variability should be considered when
      selecting TK inhibitors to treat patients.

PMID- 11839651
TI  - Evidence of determinant spreading in the antibody responses to prostate cell
      surface antigens in patients immunized with prostate-specific antigen.
AB  - PURPOSE: Prostate cancer consistently remains a difficult clinical problem. The
      development of novel therapy strategies for effective control and treatment of
      prostate cancer is essential. The prostate represents a unique site for
      immunotherapy, in part because prostate-specific immunity would most probably be
      without significant long-term sequellae. Antibodies and cell-mediated immunity,
      induced by either active or passive immunization, represent potential means to
      specifically target prostate tumor cells. EXPERIMENTAL DESIGN: The serum IgG
      response to cell surface antigens expressed on LNCAP [prostate-specific antigen
      (PSA)-positive] and PC-3 (PSA-negative) were analyzed in individuals with
      advanced disease receiving vaccinia- or fowlpox-expressed PSA (v-PSA or f-PSA,
      respectively) by flow cytometry. RESULTS: Sera from all seven patients in a Phase
      I study of v-PSA, collected prior to the third immunization, reacted with both
      prostate tumor cell lines. The majority of individuals (n = 12) in a Phase II
      trial of v-PSA and f-PSA developed sustainable antibody responses to cell surface
      antigens on the prostate tumor cell lines. The magnitude and kinetics of these
      responses were dependent on the immunization schedule. Of importance, the
      baseline serum of only one of nine patients tested had reactivity with
      nonprostate tumor cell lines. Sera from three normal males also lacked reactivity
      with prostate tumor cells. CONCLUSIONS: PSA vaccine constructs are immunogenic
      and induce antibody responses to a multitude of surface antigens on prostate
      tumor cell lines by epitope or determinant spreading after stimulation of the
      immune system by PSA immunization.

PMID- 11839652
TI  - Liposomal doxorubicin in conjunction with reirradiation and local hyperthermia
      treatment in recurrent breast cancer: a phase I/II trial.
AB  - PURPOSE: This is the first study to evaluate the tolerability and activity of
      liposomal doxorubicin (Caelyx; Schering-Plough Pharmaceuticals) < or =60 mg/km(2)
      in patients with locally recurrent breast cancer, when administered in
      conjunction with reirradiation and local hyperthermia treatment. EXPERIMENTAL
      DESIGN: Fifteen female patients, who had undergone a radical mastectomy and
      conventional radiotherapy (60 Gy) in the front chest wall, were entered on a
      multimodal protocol consisting of initial treatment with radiotherapy and a
      monthly infusion of liposomal doxorubicin < or =60 mg/m(2) in conjunction with
      local hyperthermia treatment. All patients received reirradiation up to a total
      dose of 30.6 Gy (1.8 Gy/fraction, 5 days a week). To evaluate the drug's safety,
      the first 5 patients initially received a dose of 40 mg/m(2) liposomal
      doxorubicin, which was then escalated to 60 mg/m(2). The other 10 patients
      received 60 mg/m(2) for all six cycles of chemotherapy. Hyperthermia (HT) was
      produced in the region of interest (ROI) using waveguides at a frequency of 433
      MHz. The RSS was obtained from the curves representing the change in the ROI's
      surface with time for each patient, as fitted by linear regression. Linear
      regression analysis was used to study the relationship between the time interval
      from liposomal doxorubicin infusion to HT and the RSS. RESULTS: At doses of < or
      =60 mg/m(2), liposomal doxorubicin was well tolerated, with only mild
      hematological and nonhematological toxicity. All patients showed an objective
      measurable response, with 3 patients (20%) demonstrating a clinically complete
      response. There was a significant correlation between the duration of response
      and Avg Min T(90) > 44 degrees C (r(s) = 0.917, P < 0.0001) and the Mean[Tmin]
      (r(s) = 0.909, P < 0.0001). The RSS was significantly correlated with the
      interval between liposomal doxorubicin infusion and HT, as the smaller the time
      interval, the greater the clinical benefit (r = 0.76, P = 0.001). CONCLUSIONS:
      The multimodal treatment was effective and well tolerated, producing an objective
      measurable response in all patients. Local HT had a significant effect on
      patients' response to the drug. The relationship between thermal dose and
      liposomal action requires further investigation.

PMID- 11839654
TI  - Individual adaptive dosing of topotecan in ovarian cancer.
AB  - PURPOSE: To take into account relationships between topotecan area under the
      plasma concentration (AUC) versus time curve and percentage decrease of
      neutrophil count previously shown when topotecan is administered on a 5-day,
      daily schedule. A multicentric clinical trial with individualized dosing of
      topotecan was performed in patients with platinum-refractory ovarian cancer. The
      primary goal of this study was to evaluate the toxicity of topotecan when the
      interindividual variability in plasma drug exposure is decreased. EXPERIMENTAL
      DESIGN: A total of 39 patients were evaluable. In cycle 1, the daily dose for the
      last 2 days was dependent on the observed topotecan AUC at day 1; the general
      objective was to constrain the overall AUC (i.e., from day 1 to day 5) within
      37,500-75,000 nM.min. A pharmacokinetic study was also performed on day 5 of
      cycle 1 and day 1 of cycle 2 to evaluate the intrapatient pharmacokinetic
      variability both within cycle 1 and between cycles. RESULTS: The dose of
      topotecan was decreased for 20 patients and increased for only 1 patient within
      cycle 1. The total administered dose was correlated to the creatinine clearance.
      The dose adjustments allowed control of the topotecan exposure: mean (+/-SD)
      observed AUC of 70,697 (+/-12,364) nM.min. Fourteen cases of dose-limiting
      toxicity were observed, mainly in patients who previously received two different
      regimens of chemotherapy without a washout period before topotecan treatment. An
      overall response rate of 21% was observed in the 33 patients evaluable.
      CONCLUSION: Dose adjustments are required not only in patients with creatinine
      clearance below 40 ml/min, but also in those with values between 40 and 60 ml/min
      (recommended starting dose is 1.2 mg/m(2)). By performing drug monitoring and
      taking into consideration the past treatment of each patient, better dose
      individualization can be obtained.

PMID- 11839653
TI  - Safety and efficacy of the multidrug-resistance inhibitor biricodar (VX-710) with
      concurrent doxorubicin in patients with anthracycline-resistant advanced soft
      tissue sarcoma.
AB  - PURPOSE: Incel (biricodar, VX-710) restores drug sensitivity to P-glycoprotein
      and multidrug resistance-associated protein-1-expressing cells. This Phase I/II
      study evaluated the safety/tolerability, pharmacokinetics, and efficacy of VX-710
      plus doxorubicin in patients with inoperable, locally advanced or metastatic,
      anthracycline-resistant/refractory, soft tissue sarcoma. EXPERIMENTAL DESIGN: In
      Phase I, i.v. bolus doxorubicin at 60, 75, or 67.5 mg/m(2) was administered 8 h
      after initiation of a 72-h continuous i.v. (CIV) infusion of VX-710 (120
      mg/m(2)/h) to cohorts of patients to establish a maximum tolerated dose. For
      efficacy evaluations in Phase II, eligible patients had inoperable, locally
      advanced or metastatic, anthracycline-resistant/refractory soft tissue sarcoma; <
      or =225 mg/m(2) cumulative prior doxorubicin; and adequate hematological, liver,
      and kidney function. Cycles were repeated every 3 weeks. RESULTS: Fourteen
      patients were enrolled in Phase I. Myelosuppression was the dose-limiting
      toxicity with 75 and then 67.5 mg/m(2) doxorubicin, and the maximum tolerated
      dose was established at 60 mg/m(2) with VX-710, 120 mg/m(2)/h, 72-h CIV. VX-710
      had no apparent effect on doxorubicin pharmacokinetics. Twenty-nine patients
      enrolled in Phase II were treated with VX-710, 120 mg/m(2)/h 72-h CIV, and 60
      mg/m(2) doxorubicin. Among 26 evaluable patients, minimal activity was noted
      among 11 patients with gastrointestinal stromal tumors (GISTs); however, in 15
      patients with anthracycline-resistant sarcomas of other histologies, 2 achieved
      partial responses and 7 patients had disease stabilization with an overall median
      progression-free interval of 3.4 months. CONCLUSION: Anthracycline resistance in
      GISTs appears to be independent of P-glycoprotein or multidrug resistance
      associated protein-1 resistance mechanisms. However, the combination of VX-710
      and doxorubicin resulted in objective responses or disease stabilization in
      patients with strictly defined anthracycline-refractory non-GIST sarcomas, which
      warrants further evaluation.

PMID- 11839655
TI  - Picking the winners in a sea of plenty.
AB  - PURPOSE: Selecting an experimental arm for a Phase III trial is based on the
      results of Phase II investigations. Historical results show that this paradigm
      leads to the failure of many experimental therapies in the Phase III setting.
      This is the result of failures in the Phase II design that include differences in
      the patient populations and basing sample size determinations on levels of
      benefit derived from surrogate end points that do not accurately reflect the end
      point of interest in the Phase III study. An additional factor is how to ensure
      that the experimental therapy chosen was the best available at the time.
      EXPERIMENTAL DESIGN: We consider castrate metastatic prostate cancer, for which
      multiple regimens appear to have similar activity at this time. To assess
      superiority, we use a randomized Phase II/III design developed by Schaid et al.
      (D. J. Schaid et al., Biometrika, 77: 507-513, 1990) that allows multiple
      treatments to be tested at the same time and bases the determination to proceed
      from the Phase II study on the same clinical end point evaluated in the same
      population as the Phase III trial. A concurrent control group is also treated.
      RESULTS: We demonstrate the integrative Phase II/III clinical trial design to
      evaluate two, three, or four experimental treatments with a survival-based end
      point in the same patient population. It includes a concurrent control in both
      the Phase II and Phase III portions of the study. The sample sizes in the Phase
      II component of the trial are comparable with those found in conventional single
      arm Phase II trials. CONCLUSIONS: The proposed design is valuable in situations
      where multiple regimens are available that appear worthy of evaluation in the
      Phase III setting, and where there is no adequate short-term surrogate end point
      for survival. The design is also useful in the evaluation of cytostatic agents
      where traditional response parameters may not identify potentially active drugs
      or, as is the case in advanced prostate cancer, in the evaluation of therapies
      that have a direct effect on prostate-specific antigen with an uncertain effect
      on survival.

PMID- 11839656
TI  - Continuous administration of irinotecan by hepatic arterial infusion: a phase I
      and pharmacokinetic study.
AB  - PURPOSE: The main advantage of administering chemotherapy by means of hepatic
      arterial infusion (HAI) is the achievement of a high concentration of the drug in
      the liver. Irinotecan (CPT-11) is an active agent for the treatment of advanced
      colorectal cancer and other tumor types, which frequently metastasize in the
      liver. We performed a Phase I and pharmacokinetic study to investigate CPT-11 by
      hepatic arterial administration in patients with liver metastases. PATIENTS AND
      METHODS: Patients with liver metastases received CPT-11 at doses ranging from 15
      to 25 mg/m(2)/day for 5 days every 3 weeks by continuous HAI. All of the patients
      also received one cycle CPT-11 i.v. Primary end points of the study were to
      define the maximum tolerated dose (MTD) of hepatic arterial CPT-11 and to study
      its pharmacokinetics. RESULTS: Twenty patients were included. The MTD was 25
      mg/m(2)/day and the dose-limiting toxicities were neutropenia and diarrhea. The
      metabolic ratio was significantly increased with HAI compared with i.v.
      administration (P = 0.015). The steady-state concentrations of total CPT-11 and
      CPT-11 carboxylate and lactone were all lower than those during i.v. infusion (P
      = 0.008, 0.013, and 0.004, respectively), whereas the levels of total SN-38, and
      SN-38 carboxylate, lactone, and glucuronide were similar. The total body
      clearance of CPT-11 was significantly higher with HAI (P = 0.008). CONCLUSIONS:
      The MTD of CPT-11 given by hepatic 5-day continuous infusion was 25 mg/m(2)/day.
      HAI of CPT-11 resulted in a higher metabolic ratio because of increased
      elimination of CPT-11. We recommend 20 mg/m(2)/day for additional Phase II
      studies.

PMID- 11839657
TI  - Dose escalation and pharmacokinetics of pegylated liposomal doxorubicin (Doxil)
      in children with solid tumors: a pediatric oncology group study.
AB  - PURPOSE: To determine the maximum tolerated dose and pharmacokinetics of Doxil in
      children with recurrent or refractory solid tumors. Doxil is pegylated
      doxorubicin. EXPERIMENTAL DESIGN: Eligible patients were children with refractory
      tumors who had received cumulative anthracycline doses <300 mg/m(2). Cohorts of
      at least three patients each received escalating doses of Doxil starting at 40
      mg/m(2) at 4-week intervals. If no dose-limiting toxicity occurred, dosages were
      escalated by increments of 10 mg/m(2) in subsequent cohorts. Originally, Doxil
      was administered over 60 min, but significant infusion reactions prompted longer
      infusion times of 4 h. Patients also received premedication with dexamethasone,
      ranitidine, and diphenhydramine 24 h before infusion, with ranitidine continued
      24 h after infusion. Periodic blood samples were collected and plasma doxorubicin
      concentrations were quantified to characterize the pharmacokinetics of Doxil.
      RESULTS: Between January 1997 and June 2000, 22 children ages 4-21 years with
      refractory tumors were treated with Doxil. Most patients had received one to five
      prior chemotherapy regimens, and all but five had prior radiotherapy (two had no
      prior therapy). Doxil was escalated to a dosage of 70 mg/m(2). At that level,
      dose-limiting mucositis was seen during the first cycle in two of six patients,
      thus defining dose-limiting toxicity, and in one additional patient during a
      subsequent cycle. Grade 4 neutropenia lasting less than 7 days was documented in
      two of six patients. The dose-limiting toxicity among two of six patients at 70
      mg/m(2) was grade 3 mucositis during the first cycle of therapy. Painful
      desquamating dermatitis of the hands and feet, palmar-plantar erythrodysesthesia,
      occurred in six patients. In two of those patients, palmar-plantar
      erythrodysesthesia started as grade 1 and progressed to grade 2 during subsequent
      courses. Mean estimates of central volume of distribution, clearance, and
      elimination half-life were 1.45 liters/m(2), 0.03 liter/h/m(2), and 36.4 h,
      respectively. CONCLUSION: The maximum tolerated dose of Doxil administered every
      4 weeks to pediatric patients was 60 mg/m(2). The effect of Doxil on pediatric
      patients with malignancies remains to be determined and should be studied in
      pediatric Phase II trials.

PMID- 11839658
TI  - Quantitative evaluation of somatostatin receptor subtype 2 expression in sporadic
      colorectal tumor and in the corresponding normal mucosa.
AB  - PURPOSE: The somatostatin (SS) receptor subtype 2 (sst2) is the principal
      mediator of the antiproliferative effects of SS and has the highest affinity for
      the commercially available SS analogues. The purpose of this study was to
      evaluate sst2 mRNA expression by quantitative reverse transcription-PCR (RT-PCR)
      in colon cancers and in corresponding normal tissues. EXPERIMENTAL DESIGN: The
      expression of sst2 mRNA was measured with a quantitative method based on real
      time RT-PCR with TaqMan assay in 100 colon cancers and in the corresponding
      normal tissues. In a limited number of patients, these results were compared with
      those obtained by in situ hybridization (n = 26) and by in vivo imaging with
      (111)In-pentetreotide (n = 17). RESULTS: Results obtained by quantitative RT-PCR
      on sst2 expression in colorectal cancer were significantly related to those
      obtained by in situ hybridization and (111)In-pentetreotide scintigraphy. Sst2
      was expressed in all of the tumors investigated without any relationship with
      localization, grading, and stage of disease. Although the paired, unaffected
      mucosa tends to express a higher abundance of sst2 than the corresponding cancer
      samples, this difference did not reach a statistical significance. However, in
      patients with elevated carcinoembryonic antigen levels (>5 ng/ml) there was a
      significant loss of sst2 mRNA in the tumor when compared with its paired normal
      tissue. CONCLUSIONS: In this study we confirmed, by a quantitative method, that
      colorectal cancer does not express higher concentrations of sst2 mRNA than the
      corresponding unaffected tissue. Conversely, a loss of sst2 was found in patients
      with elevated preoperative concentrations of carcinoembryonic antigen, an
      unfavorable prognostic marker for colorectal cancer.

PMID- 11839659
TI  - Breast epithelium procurement from stereotactic core biopsy washings: flow
      cytometry-sorted cell count analysis.
AB  - PURPOSE: Molecular studies of breast lesions have been constrained by
      difficulties in procuring adequate tissues for analyses. Standard procedures are
      restricted to larger, palpable masses or the use of paraffin-embedded materials,
      precluding facile procurement of fresh specimens of early lesions. We describe a
      study to determine the yield and characteristics of sorted cell populations
      retrieved in core needle biopsy specimen rinses from a spectrum of breast
      lesions. EXPERIMENTAL DESIGN: Cells from 114 consecutive stereotactic core
      biopsies of mammographic lesions released into saline washes were submitted for
      flow cytometric analysis. For each specimen, epithelial cells were separated from
      stromal and blood tissue based on the presence of cytokeratin 8 and 18 markers.
      Epithelial cell yields based on pathological diagnoses of the biopsy specimen,
      patient age, and mammographic appearance of the lesion were determined. RESULTS:
      Biopsies containing malignant lesions yielded significantly higher numbers of
      cells than were obtained from benign lesion biopsies. Significantly greater cell
      counts were observed from lesions from women age 50 or above compared with those
      of younger women. Mammographic density surrounding the biopsy site, the
      mammographic appearance of the lesion, and the number of cores taken at the time
      of biopsy appeared to have little effect on the yield of epithelial cells.
      CONCLUSIONS: We demonstrate the use of flow cytometric sorting of stereotactic
      core needle biopsy washes from lesions spanning the spectrum of breast pathology
      to obtain epithelial cells in sufficient numbers to meet the requirements of a
      variety of molecular and genetic analyses.

PMID- 11839660
TI  - High frequency of promoter hypermethylation of the death-associated protein
      kinase gene in nasopharyngeal carcinoma and its detection in the peripheral blood
      of patients.
AB  - PURPOSE: Death-associated protein (DAP)-kinase gene is frequently inactivated by
      promoter hypermethylation in cancer. The aim of this study was to evaluate the
      promoter methylation status of the DAP-kinase gene in nasopharyngeal carcinoma
      (NPC). EXPERIMENTAL DESIGN: The methylation status was evaluated by methylation
      specific PCR (MSP). Thirty-two NPC biopsy specimens, plasma and buffy coat of 12
      patients, 5 NPC cell lines, 3 normal nasopharyngeal biopsy tissues, and 2 normal
      nasopharyngeal epithelial primary cultures were included in this study. RESULTS:
      There was no promoter hypermethylation in all 3 normal nasopharyngeal tissues and
      2 normal nasopharyngeal primary cultures. Hypermethylation was found in 24 (75%)
      NPC primary tumor biopsies and 4 (80%) NPC cell lines. Of the 24 patients with
      hypermethylation of DAP-kinase promoter in the primary tumors, 12 patients had
      their plasma and buffy coat DNA available for MSP study. Hypermethylated DAP
      kinase promoter was detectable in 5 patients in the plasma but not in the buffy
      coat, 2 patients in the buffy coat but not in the plasma, and 1 patient in both
      plasma and buffy coat. Four patients had no detectable hypermethylated DAP-kinase
      promoter in both plasma and buffy coat. Hypermethylation of DAP-kinase promoter
      was found in both early- and late-stage NPC. CONCLUSIONS: Our results show that
      hypermethylation of the DAP-kinase promoter is a common early event in NPC. The
      high frequency of identification of hypermethylated DAP-kinase promoter in plasma
      and buffy coat of NPC patients illustrates its potential clinical application as
      tumor marker for the diagnosis and monitoring of treatment result.

PMID- 11839661
TI  - The role of retinoid X receptor messenger RNA expression in curatively resected
      non-small cell lung cancer.
AB  - BACKGROUND: Retinoid X receptors (RXRs) have inhibitory effects on non-small cell
      lung cancer (NSCLC) cell growth, and RXRbeta expression is reduced in NSCLC
      specimens compared with normal lung tissue. We hypothesized that suppressed RXR
      expression might be a prognostic factor of worse clinical outcome in patients
      with NSCLC. EXPERIMENTAL DESIGN: Using a quantitative real-time reverse
      transcription-PCR (TaqMan) method, we analyzed RXRalpha, RXRbeta, and RXRgamma
      mRNA expression in normal lung tissue and matching tumor samples from 88 patients
      with NSCLC. RESULTS: The median mRNA expression levels of all three RXR subtypes
      were frequently decreased in tumor tissues compared with matching normal lung
      tissue (RXRalpha, 67%; RXRbeta, 55%; RXRgamma, 89%). The RXRalpha(P = 0.001) and
      RXRgamma(P < 0.001) median expression levels were significantly lower in the
      tumors. Patients whose tumors exhibited low RXRbeta expression levels had a
      statistically significant worse overall survival (P = 0.0005), whereas a trend
      toward worse survival was observed for patients with low RXRalpha expression.
      Multivariate analysis indicated that low RXRbeta expression is an independent
      predictor of worse survival in patients with NSCLC (P = 0.017). CONCLUSION:
      Suppressed mRNA expression of all three RXR subtypes is a frequent event in
      NSCLC. Reduced RXRbeta expression might be an important biomarker for more
      aggressive disease in patients with NSCLC.

PMID- 11839662
TI  - Immunomagnetic detection of micrometastatic cells in bone marrow of colorectal
      cancer patients.
AB  - Detection of micrometastatic cells in bone marrow (BM) may potentially be of
      prognostic value in colorectal cancer (CRC). In the present study, we have
      evaluated our immunomagnetic detection method in model experiments and on BM
      samples from CRC patients. In repeated experiments, 11 of 12 CRC cell lines
      consistently bound MOC31 antibody-coated magnetic particles with an average of
      98% of the cells being rosetted with the beads. When different numbers of CRC
      cells (20, 100, 200, and 1000) were admixed to 1 x 10(7) mononuclear cells (MNCs)
      from BM, a mean of 77% of the cancer cells was recovered. In BM samples obtained
      from CRC patients at primary surgery, rosetted tumor cells were detected in 46 of
      275 samples (17%) upon screening of 2 x 10(7) MNCs/sample. The fractions positive
      were: 10% (5 of 49) in Dukes' A; 17% (20 of 115) in Dukes' B; 23% (18 of 78) in
      Dukes' C; and 9% (3 of 33) in Dukes' D. Of 206 control samples, three (1.5%)
      contained cells in BM that formed rosettes with the MOC31 beads. In positive
      samples, a median of eight tumor cells (range, 2-120) were identified per 20
      microl examined fraction, representing about one-tenth of the total sample. The
      results demonstrate the feasibility of using the immunomagnetic method for
      detection of micrometastatic CRC cells. Furthermore, that screening of 2 x 10(7)
      MNCs in a BM sample can be completed in <3 h makes the method an attractive
      alternative to other techniques.

PMID- 11839663
TI  - Expression and prognostic roles of beta-catenin in hepatocellular carcinoma:
      correlation with tumor progression and postoperative survival.
AB  - PURPOSE: Although hepatocellular carcinoma (HCC) is the most common primary
      malignant tumor of the human liver, the molecular changes and mechanisms that
      regulate its development and progression remain unclear. In the present study, we
      investigated the correlation between beta-catenin expression and clinical outcome
      in 51 patients with relatively small (maximal diameter < 30 mm), solitary HCCs.
      EXPERIMENTAL DESIGN: The tumors were classified according to histological tumor
      differentiation (grade I, 11 tumors; grade II, 28 tumors; grade III, 12 tumors).
      Using immunohistochemical methods to detect nuclear accumulation of beta-catenin,
      we investigated the correlation between beta-catenin expression and clinical
      outcome and compared the correlation with cyclin D1, Ki-67, and E-cadherin.
      RESULTS: Focal or generalized nuclear beta-catenin expression was observed in
      36.4% (4 of 11) of the grade I tumors, 39.3% (11 of 28) of the grade II tumors,
      and 25% (3 of 12) of the grade III tumors. Nuclear beta-catenin-positive grade
      III tumors were associated with significantly poorer survival (P = 0.004),
      whereas none of the patients with nuclear beta-catenin-negative grade I tumors
      died. With regard to proliferative activity, positive nuclear beta-catenin
      staining correlated significantly with an increased Ki-67 labeling index in grade
      I (P < 0.0001) and grade III (P = 0.0045) tumors and with reduced epithelial
      cadherin expression in the cell membrane (P < 0.001). In contrast, no association
      with the expression of cyclin D1, one of the target factors of beta-catenin, was
      detected. CONCLUSIONS: Our present data suggest that beta-catenin plays important
      roles in promoting tumor progression by stimulating tumor cell proliferation and
      reducing the activity of cell adhesion systems and is associated with a poor
      prognosis, especially in patients with poorly differentiated HCCs.

PMID- 11839664
TI  - RET oligonucleotide microarray for the detection of RET mutations in multiple
      endocrine neoplasia type 2 syndromes.
AB  - Multiple endocrine neoplasia type 2 (MEN2) syndromes are inherited in an
      autosomal dominant fashion with high penetrance. There are three subtypes,
      namely, MEN2A (multiple endocrine neoplasia type 2A), MEN2B (multiple endocrine
      neoplasia type 2B), and familial medullary thyroid carcinoma. The variations in
      the RET gene play an important role in the MEN2 syndromes. In this work, we have
      developed a RET oligonucleotide microarray of 67 oligonucleotides to quickly
      detect RET mutations in MEN2 syndromes. The predominant RET mutations are
      missense mutations and are restricted to nine codons (codons 609, 611, 618, 620,
      630, 634, 768, 804, and 918) in MEN2 syndromes. Missense mutations at codons 609,
      611, 618, 620, and 634 have been identified in 98% of MEN2A families and in 85%
      of familial medullary thyroid carcinoma families. More than 95% of MEN2B patients
      also had a predominant mutation type at codon 918 (Met-->Thr). RET
      oligonucleotide microarray can detect RET missense mutations at these nine
      codons. Theoretically, a total of 55 missense mutation types can occur at eight
      codons (codons 609, 611, 618, 620, 630, 634, 768, and 804). RET oligonucleotide
      microarray is designed to detect all of these 55 missense mutation types at these
      eight codons and one predominant type at codon 918. Fifty-six oligonucleotides
      were designed for the 56 mutation types at nine codons, and 11 oligonucleotides
      were designed for the wild types and positive controls. We found RET mutations in
      all eight of the Korean MEN2A families (a total of 75 members; 27 affected
      members, 19 gene carriers, and 29 unaffected members) using the developed RET
      oligonucleotide microarray and an automatic sequencing. Because we found only
      five mutation types from eight MEN2A families, the international collaborations
      are required to see whether the RET oligonucleotide microarray may be used as a
      genetic diagnostic tool. Taken together, the RET oligonucleotide microarray can
      function as a fast and reliable genetic diagnostic device, which simplifies the
      process of detecting RET mutations.

PMID- 11839665
TI  - Hypermethylation of multiple genes in tumor tissues and voided urine in urinary
      bladder cancer patients.
AB  - PURPOSE: We aimed to investigate the methylation pattern in bladder cancer and
      assess the diagnostic potential of such epigenetic changes in urine. EXPERIMENTAL
      DESIGN: The methylation status of 7 genes (RARbeta, DAPK, E-cadherin, p16, p15,
      GSTP1, and MGMT) in 98 cases of bladder transitional cell carcinoma and 4 cases
      of carcinoma in situ was analyzed by methylation-specific PCR. Twenty-two cases
      had paired voided urine samples for analysis. RESULTS: In transitional cell
      carcinoma tumor tissues, aberrant methylation was frequently detected in RARbeta
      (87.8%), DAPK (58.2%), E-cadherin (63.3%), and p16 (26.5%), whereas methylation
      of p15 (13.3%), GSTP1 (5.1%), and MGMT (5.1%) is not common. No association
      between methylation status and grading or muscle invasiveness was demonstrated.
      In 22 paired voided urine samples of bladder cancer, methylation of DAPK,
      RARbeta, E-cadherin, and p16 could be detected in 45.5%, 68.2%, 59.1%, and 13.6%
      of the cases, respectively. The sensitivity of methylation analysis (90.9%) was
      higher than that of urine cytology (45.5%) for cancer detection. Methylation of
      RARbeta(50%), DAPK (75%), and E-cadherin (50%) was also detected in carcinoma in
      situ. In 7 normal urothelium samples and 17 normal urine controls, no aberrant
      methylation was detected except for RARbeta methylation in 3 normal urothelium
      samples (42.9%) and 4 normal urine samples (23.5%), respectively. CONCLUSIONS:
      Our results demonstrated a distinct methylation pattern in bladder cancer with
      frequent methylation of RARbeta, DAPK, E-cadherin, and p16. Detection of gene
      methylation in routine voided urine using selected markers appeared to be more
      sensitive than conventional urine cytology.

PMID- 11839666
TI  - Hypoxia-induced, perinecrotic expression of endothelial Per-ARNT-Sim domain
      protein-1/hypoxia-inducible factor-2alpha correlates with tumor progression,
      vascularization, and focal macrophage infiltration in bladder cancer.
AB  - Endothelial Per-ARNT-Sim (PAS) domain protein-1 (EPAS-1)/hypoxia-inducible factor
      2alpha (HIF-2alpha) is a member of the basic helix-loop-helix/PAS domain protein
      family and is considered to be an endothelial-specific, hypoxia-inducible
      transcription factor. Because hypoxia is a fundamental element of tumor biology
      determining clinical outcome, we performed an immunohistochemical study of EPAS-1
      expression in a cohort of bladder cancer cases and assessed the possible
      correlation of EPAS-1 expression with tumor hypoxia and growth. In the 67 cases
      (37 radical cystectomy and 30 transurethral resection) studied, overexpression of
      EPAS-1/HIF-2alpha protein was not found in cancer cells or in normal tissues but
      was mostly found in stroma around cancer cells, and strong positive staining was
      noted in perinecrotic regions. The perinecrotic/tumorous expression of EPAS-1/HIF
      2alpha was correlated statistically with higher histological grade (P < 0.001),
      advanced pathological T stage (P < 0.001), and presence of necrosis (P < 0.001).
      A parallel immunohistochemical analysis of a marker gene of vascular endothelial
      growth factor demonstrated its positive correlation with tumor grade, stage, and
      EPAS-1/HIF-2alpha overexpression, supporting the correlation of EPAS-1/HIF-2alpha
      up-regulation with tumor angiogenesis. To further clarify the relationship
      between hypoxia and vascularity in the perinecrotic/tumorous area with EPAS-1/HIF
      2alpha expression, tissue microvessel density (MVD) was assessed. No significant
      correlation (P = 0.442) was found between EPAS-1/HIF-2alpha expression and MVD if
      the 67 tumors of different stages were all included. However, EPAS-1/HIF-2alpha
      positive cases had lower MVD than EPAS-1/HIF-2alpha-negative cases (P = 0.001) if
      only invasive cancer cases were analyzed. In addition, in all EPAS-1/HIF-2alpha
      positive staining cases, EPAS-1/HIF-2alpha-positive foci had lower MVD than EPAS
      1/HIF-2alpha-negative foci (P < 0.001). Finally, using serial sections, the
      location of EPAS-1/HIF 2alpha expression was identified mainly in tumor
      associated macrophage (TAM) as well as in some fibroblast cells. Focal TAM
      infiltration was identified at a higher level in EPAS-1-positive cases than EPAS
      1-negative cases (P < 0.001). This is the first clinical report suggesting that
      hypoxia-induced, perinecrotic EPAS-1/HIF-2alpha expression is correlated with
      tumor progression and angiogenesis at higher grade and stage through focal TAM
      infiltration in invasive bladder cancer.

PMID- 11839667
TI  - Mitochondrial D-loop mutations as clonal markers in multicentric hepatocellular
      carcinoma and plasma.
AB  - PURPOSE: Hepatocellular carcinoma (HCC) is a highly malignant tumor prone to
      multicentric occurrence. Differentiation between a true relapse of HCC and a
      second primary tumor is of clinical importance. We sought to identify
      mitochondrial mutations in HCC and test their use as clonal markers in this
      disease. EXPERIMENTAL DESIGN: Primary HCC tissue samples were obtained from 19
      patients and analyzed for mutations within the mitochondrial displacement loop (D
      loop). The discovered mutations were used to determine tumor clonality and
      provided the basis for detection of tumor DNA in corresponding plasma samples.
      RESULTS: Thirteen of 19 HCC cases (68%) were identified as having D-loop
      mitochondrial DNA (mtDNA) mutations in at least one tumor. In 3 of these 13
      cases, the same mutation was observed in multiple tumors, indicating monoclonal
      origin. Remarkably, in 8 of 13 mutated cases, we detected deletion/insertion
      mutations in the C-tract, a recently reported hotspot and potential replication
      start site of the closed, circular mitochondrial genome. In addition, we detected
      mutant mtDNA in 8 of 10 tested paired plasma DNA samples using a highly
      sensitivity molecular assay. CONCLUSIONS: mtDNA mutations within the D-loop
      control region are a frequent event in HCC, providing a molecular tool for the
      determination of clonality. In addition, detection of tumor-specific mtDNA
      mutations in plasma DNA needs to be explored further for monitoring patients with
      primary HCC.

PMID- 11839668
TI  - BAX expression in Hodgkin and Reed-Sternberg cells of Hodgkin's disease:
      correlation with clinical outcome.
AB  - PURPOSE: BAX, a proapoptotic member of the BCL-2 family of proteins, has been
      detected in Hodgkin and Reed-Sternberg (HRS) cells of Hodgkin's disease (HD), but
      its clinical significance is unknown. Therefore, we correlated BAX expression
      with presenting features and clinical outcome in untreated patients with HD.
      DESIGN: Patients with biopsy-proven HD were eligible if they were untreated
      previously and if pretreatment paraffin-embedded tumor tissue was available. BAX
      was detected by immunohistochemistry without knowledge of clinical features or
      outcome. A tumor was considered as positive if any number of HRS cells expressed
      BAX, but other cutoffs of BAX expression were examined for analysis of clinical
      outcome. RESULTS: We identified 260 patients with HD. The median age was 31
      years, and 55% were male. HRS cells expressed BAX in 181 of 195 (93%) nodular
      sclerosis, 47 of 48 (98%) mixed cellularity, 1 case of lymphocyte depletion, all
      6 unclassified classical HD, and all 10 lymphocyte predominance tumors. Using a
      cutoff of 50% positive HRS cells for BAX expression, the 5-year failure-free
      survival (FFS) for patients with high versus low BAX expression was 83 versus
      93%, respectively (P = 0.19 by Log-rank) for 116 patients treated with
      doxorubicin, bleomycin, vinblastine, and dacarbazine or equivalent regimens; it
      was 78 versus 79%, respectively, for 79 patients treated with mitoxantrone,
      vincristine, vinblastine, and prednisone and radiotherapy (P = 0.45 by Log-rank);
      it was 71 versus 81%, respectively, for 26 patients treated with nitrogen
      mustard, vincristine, prednisone, and procarbazine (P = 0.6 by Log-rank); and it
      was 72 versus 82% for 29 patients treated only with radiotherapy (P = 0.57 by Log
      rank). The 5-year FFS was not statistically different when we used cutoffs of 20,
      30, and 75% for BAX expression. CONCLUSION: BAX is often expressed by HRS cells
      in HD and does not correlate with FFS.

PMID- 11839670
TI  - Intraclonal homogeneity of clonotypic immunoglobulin M and diversity of
      nonclinical post-switch isotypes in multiple myeloma: insights into the evolution
      of the myeloma clone.
AB  - PURPOSE: The transformation status and role of clonotypic pre-switch IgM in the
      evolution of malignant post-switch multiple myeloma (MM) cells is unclear. In
      this study, we determined the differentiation stage within the B lineage of
      clonotypic cells from malignant and nonclinical isotype pools by analyzing the
      frequency and intraclonal diversity of members within each isotype pool. RESULTS:
      Immunoglobulin VDJ transcripts were amplified from peripheral blood cells of
      seven patients with a hemi-nested reverse transcription-PCR with complementarity
      determining region 1 (CDR1)-specific and constant region primers. Of the 1951
      clones screened by patient CDR2/3-specific PCR, 356 of these were sequenced.
      Intraclonal homogeneity was observed in pre-switch transcripts from four of four
      informative patients. Transcripts from the IgM pool were relatively frequent in
      two of four informative patients. Cellular limiting dilution analysis indicated
      0.4-25% of peripheral blood mononuclear cells expressed clonotypic IgM for 6 of
      15 samples tested. By contrast, significant intraclonal diversity was observed in
      the nonclinical IgA pool of 1 patient. A genealogical tree of IgA sequences was
      constructed showing ongoing clonal diversification from sequences with close
      homology to the germ-line V gene to those resembling the PC sequence.
      Furthermore, some clones exhibited complete homology with tumor VDJ sequence,
      plus extra mutations, suggestive of a parallel clonal arm that remains responsive
      to an antigenic stimulus. CONCLUSIONS: Detection of intraclonal diversity in the
      post-switch nonclinical isotype pool suggests that remnants of the parent B-cell
      clone coexist with malignant clonal precursors. The presence of intraclonal
      homogeneity in the pre-switch IgM pool supports the idea that pre-switch MM cells
      play a role in malignant events within the MM clone.

PMID- 11839669
TI  - p63 expression profiles in human normal and tumor tissues.
AB  - PURPOSE: The p63 gene, located on chromosome 3q27-28, is a member of the p53 gene
      family. The product encoded by the p63 gene has been reported to be essential for
      normal development. EXPERIMENTAL DESIGN: In this study, we examined the
      expression pattern of p63 in human normal and tumor tissues by
      immunohistochemistry using a monoclonal antibody (clone 4A4) that recognizes all
      p63 splice variants, and by reverse transcription-PCR using isoform-specific
      primers. RESULTS: We found that p63 expression was restricted to the nucleus,
      with a nucleoplasmic pattern. We also observed that the expression was restricted
      to epithelial cells of stratified epithelia, such as skin, esophagus, exocervix,
      tonsil, and bladder, and to certain subpopulations of basal cells in glandular
      structures of prostate and breast, as well as in bronchi. Consistent with the
      phenotype observed in normal tissues, we found that p63 is expressed
      predominantly in basal cell and squamous cell carcinomas, as well as transitional
      cell carcinomas, but not in adenocarcinomas, including those of breast and
      prostate. Interestingly, thymomas expressed high levels of p63. Moreover, a
      subset of non-Hodgkin's lymphoma was also found to express p63. Using isoform
      specific reverse transcription-PCR, we found that thymomas express all isoforms
      of p63, whereas the non-Hodgkin's lymphoma tended to express the transactivation
      competent isoforms. We did not detect p63 expression in a variety of endocrine
      tumors, germ cell neoplasms, or melanomas. Additionally, soft tissue sarcomas
      were also found to have undetectable p63 levels. CONCLUSIONS: Our data support a
      role for p63 in squamous and transitional cell carcinomas, as well as certain
      lymphomas and thymomas.

PMID- 11839671
TI  - Aberrant promoter methylation profile of prostate cancers and its relationship to
      clinicopathological features.
AB  - PURPOSE: We investigated the aberrant methylation profile of prostate cancers and
      correlated the data with clinical findings. EXPERIMENTAL DESIGN: Gene promoter
      methylation was analyzed in 101 prostate cancer samples. In addition, we analyzed
      32 nonmalignant prostate tissue samples, which included 25 with benign disease,
      benign prostatic hypertrophy, or prostatitis, and 7 normal tissues adjacent to
      cancer. The methylation status of 10 genes was determined. The methylation index
      (MI) was calculated as a reflection of the methylated fraction of the genes
      examined. RESULTS: Methylation percentages of the genes tested in prostate
      cancers were: RARbeta, 53%; RASSF1A, 53%; GSTP1, 36%; CDH13, 31%; APC, 27%; CDH1,
      27%; FHIT, 15%; p16(INK4A), 3%; DAPK, 1%; and MGMT, 0%. Methylation percentages
      in nonmalignant tissues were much lower. For clinicopathological correlations, we
      divided the cancer cases into low (6 or less) or high (7 or more) Gleason score
      (GS) groups, and into low (8 ng/ml or less) or high (greater than 8 ng/ml)
      preoperative serum prostate-specific antigen (PSA) groups. Methylation of
      RASSF1A, GSTP1, RARbeta, and CDH13 genes was significantly more frequent in the
      high GS group than in the low GS group. Methylation of RASSF1A, CDH1, and GSTP1
      genes was significantly more frequent in the high PSA group than in the low PSA
      group. The median MIs were significantly higher in the high GS and the high PSA
      groups. According to the Spearman rank-correlation test, there was significant
      correlation between MI and GS (coefficient = 0.43, P < 0.0001) and the
      preoperative serum PSA (coefficient = 0.37, P = 0.0003). CONCLUSIONS: Our results
      indicate that the methylation profile of prostate cancers correlates with
      clinicopathological features of poor prognosis.

PMID- 11839672
TI  - HER-2-positive breast carcinomas as a particular subset with peculiar clinical
      behaviors.
AB  - PURPOSE: The association between HER-2-positivity, and prognostic variables and
      survival have been addressed in many studies with still controversial results
      because of the small series analyzed. EXPERIMENTAL DESIGN: A series of 1928
      primary breast carcinomas was analyzed for the prognostic potential of HER-2
      overexpression. RESULTS: In our series, HER-2-positivity was not associated with
      nodal status, unless the number of infiltrated nodes was considered, whereas it
      was strongly associated with large tumors (P < 10(-4)), grade III tumors (P < 10(
      4)), lymphoid infiltration (P < 10(-4)), and absence of hormone receptor
      expression (P < 10(-4)). HER-2 overexpression was a strong prognostic indicator
      in N+ patients (P < 10(-7)), whereas its prognostic impact was weak and not
      statistically significant in the N- patients. Analysis of the hazard ratio of
      relapse in relation to time from surgery indicates that the poor prognosis
      associated with HER-2 positivity in N+ patients was found to be attributable to a
      peak of relapses in the first 3-4 years from surgery. Multivariate analysis of
      different prognostic factors in HER-2+ and HER-2- subsets indicated that grade is
      the most important factor followed by nodal status, lymphoid infiltration, and
      tumor size in HER-2-negative breast carcinomas, whereas nodal status was the most
      important prognostic factor, with tumor size showing only borderline
      significance, in the HER-2-positive group. CONCLUSIONS: Together, the results
      indicate that HER-2-positive breast carcinomas represent a particular subset of
      tumors with peculiar clinical and pathological behaviors. Thus, conclusions drawn
      from clinical trials, which serve as the basis for clinical management of breast
      carcinomas, might not always be valid for this low-frequency subset.

PMID- 11839673
TI  - Gain of 5p15 detected by comparative genomic hybridization as an independent
      marker of poor prognosis in patients with esophageal squamous cell carcinoma.
AB  - Comparative genomic hybridization was applied to 51 primary esophageal squamous
      cell carcinomas (ESCCs) to clarify the relation between DNA sequence copy number
      aberrations (DSCNAs) and the clinicopathology of the disease. The average number
      of DSCNAs was 10.9 DSCNAs/tumor (6.1 gains and 4.9 losses), ranging from 1-30
      DSCNAs/tumor. Gain of 3q26-qter and loss of 18q22-qter were detected in >60% of
      stage I tumors and considered to play an important role in the development of
      ESCC. Whereas gain of 8q24-qter was observed in 82.6% (19 of 23) of stage III and
      IV cancers, it was seen in 27.3% (3 of 11) of stage I tumors. It is suggested
      that gain of 8q24-qter plays an important role in tumor progression. Gains of
      8q24-qter and 20q12-qter and loss of 11q22-23 were linked to nodal metastasis (P
      = 0.0006, 0.002, and 0.02, respectively). Gains of 5p15 and 14q21 were associated
      with distant organ metastasis after surgery (P = 0.006 and 0.02, respectively).
      These observations suggest that nodal and distant organ metastases involve
      different genes. Gains of 5p15, 8q24-qter, and 14q21 were significantly
      associated with unfavorable prognosis (P = 0.0002, 0.007, and 0.04,
      respectively). Multivariate analysis revealed the 5p15 gain to be an independent
      prognostic marker with a higher significance than that of nodal status (risk
      ratio = 5.95; P = 0.001). The present findings indicate that comparative genomic
      hybridization analysis may be used to predict the likelihood of a poor or
      favorable outcome in cases of ESCC.

PMID- 11839674
TI  - Detection of genetic prognostic markers in uveal melanoma biopsies using
      fluorescence in situ hybridization.
AB  - PURPOSE: In uveal melanoma, specific chromosomal abnormalities are known to
      correlate with the risk of metastases; changes in chromosomes 3 and 8q correlate
      strongly with a decreased survival of the patient, whereas chromosome 6
      abnormalities are associated with a better prognosis. Usually, karyotyping and
      fluorescence in situ hybridization (FISH) analysis are used to detect these
      abnormalities in resected tumor tissues. However, the evaluation of these
      chromosomal changes is compromised in patients treated with eye-retaining
      treatment protocols because of the lack of tumor material. The purpose of this
      study was to validate the use of FISH for the analysis of genetic prognostic
      markers. EXPERIMENTAL DESIGN: We analyzed 40 uveal melanoma fine needle
      aspiration biopsies (FNABs) and the corresponding main tumor with FISH. RESULTS:
      All biopsies were found to contain tumor cells, and FISH analyses of the samples
      were successful in all cases. Statistical analysis showed very good agreement
      between the FISH results from the biopsies and those from the main tumor. In only
      2 of 249 hybridizations did we find a small variation that could have led to a
      misclassification. CONCLUSIONS: Our results indicate that the application of FISH
      to FNABs is a reliable method for assaying genetic prognostic parameters such as
      chromosome 3 loss and/or chromosome 8q gain. Implementation of this method in a
      diagnostic setting means that we are able to identify patients at risk of
      developing metastatic disease, not only in enucleated patients but also in cases
      treated with conservative treatment modalities such as radiotherapy.

PMID- 11839675
TI  - Characterization of the HER-2/neu oncogene by immunohistochemical and
      fluorescence in situ hybridization analysis in oral and oropharyngeal squamous
      cell carcinoma.
AB  - PURPOSE: The role of HER-2/neu in squamous cell carcinoma (SCC) of the head and
      neck is not well defined. The purpose of the current study is to measure the
      frequency of HER-2/neu expression, to demonstrate HER-2/neu gene amplification in
      the cases found to be positive for protein overexpression, and to investigate the
      prognostic significance of overexpression and/or amplification in SCC of the head
      and neck. EXPERIMENTAL DESIGN: A cohort of 77 patients with SCC of the oral
      cavity or oropharynx, with stage III or IV disease and uniformly treated with
      surgical resection and postoperative radiation, served as the primary patient
      population for the study. Of these, 56 patients had adequate follow-up and
      paraffin-embedded specimens available for analysis. Median follow-up was 6.1
      years. Each of the paraffin-embedded specimens were immunohistochemically stained
      for HER-2/neu expression and graded for intensity of staining by a pathologist.
      All cases that demonstrated positive staining by immunohistochemistry were
      analyzed by fluorescence in situ hybridization (FISH) to assess HER-2/neu
      amplification status. RESULTS: Five-year survival for the 56 evaluable patients
      was 40%, with 25% experiencing local relapse, 18% regional relapse, and 25%
      distant relapse. The percentage of tumors staining positive for HER-2/neu by
      immunohistochemistry was 17%. There was no statistically significant correlation
      between HER-2/neu and T stage, N stage, tumor grade, survival, or disease-free
      survival. HER-2/neu expression did correlate with vascular endothelial growth
      factor expression. FISH analysis revealed four cases that were amplified for HER
      2/neu. Of note, of the 4 amplified cases, 2 suffered regional relapse, 1 suffered
      distant metastasis, and all 4 expired by 5 years of follow-up. CONCLUSIONS: This
      is the first demonstration of HER-2/neu gene amplification by FISH in SCC of the
      head and neck. FISH validates a previously contested controversial role for HER
      2/neu gene overexpression in SCC of the head and neck. The prognostic
      significance and clinical implications of HER-2/neu expression and amplification
      in head and neck cancer will require additional studies.

PMID- 11839676
TI  - Utilization of the human genome sequence localizes human papillomavirus type 16
      DNA integrated into the TNFAIP2 gene in a fatal cervical cancer from a 39-year
      old woman.
AB  - PURPOSE: The purpose of our study was to characterize a human papillomavirus
      (HPV) 16 DNA integration in the genome of a rapidly progressive, lethal cervical
      cancer in a 39-year-old woman. EXPERIMENTAL DESIGN: An HPV 16 integration site
      from cervical cancer tissue was cloned and analyzed using Southern blot
      hybridization, nucleotide sequencing, fluorescence in situ hybridization analysis
      for chromosomal localization and comparison with the draft human genome sequence.
      RESULTS: HPV 16 DNA (3826 bp) was integrated into the genome of the tumor sample
      and contained an intact upstream regulatory region and E6 and E7 open reading
      frames. Both 5' and 3' viral-cell junction regions contained direct repeat and
      palindrome sequences. The chromosomal location of the viral integration and
      cellular deletion was mapped to chromosome 14q32.3 using both a somatic cell
      hybrid panel and fluorescence in situ hybridization. Search of the draft human
      genome sequence confirmed the chromosomal location and revealed a disruption of
      the TNFAIP2 cytokine/retinoic acid-inducible gene. CONCLUSIONS: On the basis of
      the lack of sequence homology between the viral and cellular site of integration
      and the structure of the viral-cell junctions, it seems that HPV 16 DNA
      integrates into the host genome by a mechanism of nonhomologous recombination. We
      suggest that, taken together, maintenance of E6 and E7 expression, loss of the E2
      gene and disruption of the TNFAIP2 gene through viral integration contributed to
      the rapid progression of cervical cancer in this patient. Availability of the
      human genome sequence will facilitate identification of cellular genes involved
      in cervical cancer by high-throughput analysis of viral integration sites.

PMID- 11839677
TI  - The Ras inhibitor S-trans,trans-farnesylthiosalicylic acid chemosensitizes human
      tumor cells without causing resistance.
AB  - Ras transformation requires Ras membrane anchorage, which is promoted by a
      farnesylcysteine carboxymethyl ester and by additional sequences specific to each
      Ras isoform. We showed previously that S-trans,trans-farnesylthiosalicylic acid
      (FTS) disrupts Ras membrane anchorage and that this disturbance contributes to
      inhibition of cell transformation and tumor growth. Most tumor cells develop
      resistance to anticancer agents. Here we examined whether tumor cells develop
      resistance to FTS and evaluated the therapeutic potential of FTS combined with
      cytotoxic drugs, because oncogenic Ras promotes antiapoptotic signals in tumors
      of epithelial origin. We showed that Panc-1 pancreatic cancer cells, SW480 colon
      cancer cells, and H-ras (EJ)-transformed Rat-1 fibroblasts exposed to FTS for
      prolonged periods (>6 months) do not escape FTS-induced growth inhibition and do
      not develop drug resistance. These cells continued to express reduced amounts of
      Ras, exhibit a reversed phenotype, and show an altered response to the cytotoxic
      drugs doxorubicin and gemcitabine. FTS-treated Panc-1 or SW480 cells acquired
      sensitivity to the cytotoxic drugs, whereas FTS-treated EJ cells lost sensitivity
      to doxorubicin, reflecting the opposite effects of oncogenic Ras on the survival
      of epithelial cells and fibroblasts. Treatment with FTS led to a marked increase
      in sensitivity to gemcitabine of the formerly resistant SW480 cells and a 100
      fold increase in sensitivity to gemcitabine of Panc-1 cells. Such treatment in
      mice with preexisting Panc-1 tumors provided a synergistic effect of FTS and
      gemcitabine, leading to enhanced inhibition of tumor growth and a 65% increase in
      survival rate.

PMID- 11839678
TI  - Arsenic trioxide cytotoxicity in steroid and chemotherapy-resistant myeloma cell
      lines: enhancement of apoptosis by manipulation of cellular redox state.
AB  - PURPOSE: We investigated the ability of pretreatment with buthionine sulfoximine
      (BSO) to overcome a priori resistance to arsenic trioxide (As(2)O(3)) in multiple
      myeloma (MM) cells and determine whether this was through an apoptotic mechanism
      that involves changes in the cellular redox state. EXPERIMENTAL DESIGN: Using a
      panel of dexamethasone and chemotherapy-resistant MM cell lines, we examined
      growth inhibition, induction of apoptosis, and changes in the redox state by
      As(2)O(3) alone or after preincubation with BSO. RESULTS: Whereas the sensitive
      cell lines showed 100% killing at 0.5 micromol/liter of As(2)O(3), the resistant
      cell lines required BSO pretreatment to achieve 100% killing at this dose. By
      comparison, the peak As(2)O(3) plasma concentration in acute promyelocytic
      leukemia in patients successfully treated was 5-7 micromol/liter with rapid
      decline to a sustained level of 1-2 micromol/liter. We demonstrated that BSO and
      As(2)O(3)-induced cytotoxicity was attributable to induction of apoptosis
      accompanied by activation of the death signals: caspases 3, 8, and 9.
      CONCLUSIONS: We have demonstrated that growth inhibition of highly resistant MM
      cell lines by As(2)O(3) is facilitated by BSO and that this effect is accompanied
      by caspase activation, presumably leading to activation of apoptosis. These data
      indicate that steroid and chemotherapy-resistant MM cell lines can be overcome by
      manipulation of the cellular redox state. Because BSO and As(2)O(3) can be used
      at clinically relevant concentrations, we believe that our observations may have
      important implications for the treatment of MM.

PMID- 11839679
TI  - Superior therapeutic profile of poly-L-glutamic acid-paclitaxel copolymer
      compared with taxol in xenogeneic compartmental models of human ovarian
      carcinoma.
AB  - Previous preclinical studies with ectopic tumor models have demonstrated
      remarkable improvements in the therapeutic profile of paclitaxel, formulated as a
      copolymer with poly-L-glutamic acid, compared with paclitaxel in the clinical
      formulation, Taxol. In this study, we evaluated these formulations in two human
      ovarian carcinoma xenograft models, NMP-1 and HEY, in nude mice. i.p.
      implantation in female nude mice of either cell line gave rise to progressive
      disease within the peritoneum, in the parenchyma of visceral organs, and
      eventually at extraperitoneal sites; the resultant, increasing morbidity then
      required host sacrifice. i.p. administration of multiple-dose Taxol at its
      maximum tolerated dose 1 week after tumor implantation afforded minimal or no
      increased survival compared with controls in either model. Consistent with the
      predictions of drug copolymer behavior, paclitaxel, as the poly-L-glutamic acid
      paclitaxel copolymer, displayed much less toxicity than Taxol in these hosts.
      When evaluated for antitumor efficacy in both the Taxol-resistant NMP-1 and HEY
      models, significant improvement in survival, and even some cures, were observed
      after a single i.p. treatment with this copolymer. The observed antitumor
      response correlated with histopathological analysis of peritoneal and
      extraperitoneal tumor burden in comparing control HEY mice sacrificed near the
      onset of morbidity with mice receiving paclitaxel copolymer. We conclude that
      both the i.p. NMP-1 and HEY models have significant value in establishing the
      efficacy of candidate agents, which might address Taxol-resistant human ovarian
      carcinoma. Furthermore, the poly-L-glutamic acid-paclitaxel copolymer has a
      superior therapeutic profile in these Taxol-resistant compartmental models.

PMID- 11839680
TI  - MS-209, a quinoline-type reversal agent, potentiates antitumor efficacy of
      docetaxel in multidrug-resistant solid tumor xenograft models.
AB  - The existence of multidrug-resistant (MDR) cells in cancer is a major obstacle to
      effective cancer chemotherapy. Expression of P-glycoprotein (P-gp) in cancer
      cells causes resistance against paclitaxel and docetaxel, as well as against
      vincristine and doxorubicin (ADM). MS-209 is a novel MDR-reversal agent currently
      under clinical evaluation, which is shown to be active against ADM and
      vincristine resistance in MDR cancer cells in vitro and in vivo. In this paper,
      we report the combined effect of MS-209 with docetaxel in various MDR cancer cell
      lines that express P-gp. MS-209 at 3 microM effectively overcame docetaxel
      resistance in MDR cancer cells, and this concentration was achieved in blood
      plasma for > 7 h without serious toxicity. To study the effect of MS-209 in a
      clinically relevant model, we compared the antitumor efficacy of docetaxel alone
      with that of docetaxel combined with MS-209 at equitoxic doses in established
      solid tumor xenograft models. Treatment with docetaxel alone at the maximal
      tolerated dose (MTD) showed an apparent antitumor activity to an intrinsically
      resistant HCT-15 tumor xenograft, and MS-209 additionally potentiated the
      antitumor activity of docetaxel. Against a MCF-7/ADM tumor xenograft expressing
      larger amounts of P-gp, docetaxel alone at the MTD showed no antitumor activity,
      whereas the MTD of docetaxel combined with MS-209 greatly reduced MCF-7/ADM tumor
      growth. These results indicate that MS-209 could be a clinically useful drug to
      modulate MDR in docetaxel therapy.

PMID- 11839681
TI  - Inhibition of PDE3B augments PDE4 inhibitor-induced apoptosis in a subset of
      patients with chronic lymphocytic leukemia.
AB  - PURPOSE: cAMP phosphodiesterase (PDE) 4 is a family of enzymes the inhibition of
      which induces chronic lymphocytic leukemia (CLL) apoptosis. However, leukemic
      cells from a subset of CLL patients are relatively resistant to treatment with
      the PDE4 inhibitor rolipram, particularly when this drug is used in the absence
      of an adenylate cyclase stimulus such as forskolin. Elevated cAMP levels induce
      compensatory up-regulation of several cyclic nucleotide PDE families in other
      model systems. We here examine the hypothesis that CLL cells that survive
      treatment with rolipram do so as a result of residual PDE activity that is not
      inhibited by this drug. EXPERIMENTAL DESIGN: We examined by Western analysis the
      effect of rolipram treatment on CLL expression of PDE3B, PDE4A, PDE4B, PDE4D, and
      PDE7A. We also examined the ability of rolipram (PDE4 inhibitor) or cilostamide
      (PDE3 inhibitor), alone or together, to induce apoptosis or elevate cyclic AMP in
      leukemic cells from patients with CLL. RESULTS: Rolipram increased levels of
      PDE4B and, to a variable extent, PDE4D. When combined with forskolin, rolipram
      also increased levels of a second family of PDEs, PDE3B. Addition of the specific
      PDE3 inhibitor, cilostamide, modestly augmented rolipram-induced apoptosis in
      five of seven "rolipram-resistant" CLL samples. CONCLUSIONS: Although this work
      confirms that PDE4 appears to be the most important PDE target for induction of
      apoptosis in CLL, combination therapy with PDE3 and PDE4 inhibitors or use of
      dual-selective drugs may be of benefit in a subset of relatively PDE4-inhibitor
      resistant CLL patients.

PMID- 11839682
TI  - Paclitaxel triggers cell death primarily via caspase-independent routes in the
      non-small cell lung cancer cell line NCI-H460.
AB  - PURPOSE: Here we report on the role of mitochondria, death receptors (DRs), and
      caspases in exerting the cytotoxic effect of clinically relevant concentrations
      of paclitaxel in the non-small cell lung cancer cell line NCI-H460. EXPERIMENTAL
      DESIGN: We have characterized paclitaxel-induced cell death with annexin V,
      propidium iodide staining, and poly(ADP-ribose) polymerase cleavage assays. The
      involvement of the mitochondria pathway was studied by monitoring cytochrome c
      release and using H460 cells stable in overexpressing Bcl-2 or Bcl-x(L). DR
      dependency was analyzed in FADD dominant-negative or cytokine response modifier A
      overexpressing cells, and a possible role for DR4 and DR5 was investigated by
      antagonistic antibodies. Caspase activity and cleavage assays and treatment with
      the synthetic inhibitor zVAD-fmk were used to determine the involvement of
      caspases. RESULTS: Paclitaxel-treated cells displayed several features of
      apoptosis, including annexin V staining and poly(ADP-ribose) polymerase cleavage.
      The sequence of events suggested the involvement of a DR, as indicated by an
      early role for Fas-associated death domain and caspase-8, followed by cleavage of
      Bid and the disruption of mitochondria; nonetheless, we failed to demonstrate the
      involvement of DR4 and DR5. Interestingly, inhibition of either one of these
      routes only resulted in a 30% reduction of cell death that was in line with the
      observed small effect of caspase inhibition by zVAD-fmk on H460 cell survival.
      CONCLUSION: Paclitaxel triggers cell death in H460 cells mainly via a currently
      unidentified caspase-independent mechanism in which the basic apoptotic machinery
      is merely coactivated. This finding is in sharp contrast with the largely caspase
      dependent response elicited by DNA-damaging agents in these cells. We speculate
      on therapeutic implications.

PMID- 11839683
TI  - Protein kinase A RIalpha antisense inhibition of PC3M prostate cancer cell
      growth: Bcl-2 hyperphosphorylation, Bax up-regulation, and Bad
      hypophosphorylation.
AB  - It has been shown that expression of the RIalpha subunit of cyclic AMP (cAMP)
      dependent protein kinase is enhanced in human cancer cell lines, primary tumors,
      and cells after transformation. Using an antisense strategy, we have shown that
      RIalpha has a role in neoplastic cell growth in vitro and in vivo. In the present
      study, we have investigated the sequence- and target-specific effects of
      exogenous RIalpha antisense oligodeoxynucleotides (ODNs) and endogenous antisense
      gene on tumor growth, apoptosis, and cAMP signaling in androgen-insensitive
      prostate cancer cells, both in vitro and in nude mice. Here, we show that an
      RIalpha antisense, RNA/DNA mixed backbone ODN exerts a reduction in RIalpha
      expression at both the mRNA and protein levels, up-regulation of both the RIIbeta
      subunit of cAMP-dependent protein kinase or protein kinase A and c-AMP
      phosphodiesterase IV expression, and inhibition of cell growth. Growth inhibition
      was accompanied by changes in cell morphology and the appearance of apoptotic
      nuclei. In addition, Bcl-2 hyperphosphorylation; increase in the proapoptotic
      proteins Bax, Bak, and Bad; and Bad hypophosphorylation occurred in the antisense
      treated cells. These effects of exogenously supplied antisense ODN mirrored those
      induced by endogenous antisense gene overexpression. The RIalpha antisense ODNs,
      which differed in sequence or chemical modification, promoted a sequence- and
      target-specific reduction in RIalpha protein levels and inhibited tumor growth in
      nude mice. These results demonstrate that in a sequence-specific manner, RIalpha
      antisense, via efficient depletion of the growth stimulatory molecule RIalpha,
      induces growth inhibition, apoptosis, and phenotypic (cell morphology) changes,
      providing an innovative approach to combat hormone-insensitive prostate cancer
      cell growth.

PMID- 11839684
TI  - Automated electrorotation to reveal dielectric variations related to HER-2/neu
      overexpression in MCF-7 sublines.
AB  - PURPOSE: Electrorotation (ROT) is a technique that allows for determination of
      the dielectric properties of living cells when exposed to a rotating electric
      field. We evaluated the ROT behavior of MCF/neo and p185(neu) transfectancts
      MCF/HER2-11 and MCF/HER2-18 to investigate whether differences in HER-2/neu
      expression were associated with differences in dielectric properties in these
      cells. EXPERIMENTAL DESIGN: P185(neu) was measured by Western blotting in MCF/neo
      cells and HER-2/neu transfectants MCF/HER2-11 and MCF/HER2-18. ROT spectra and
      cell membrane-specific capacitance were obtained for each cell line. RESULTS: The
      mean cell membrane-specific capacitance values for MCF/neo, MCF/HER2-11, and
      MCF/HER2-18 were 2.09, 1.70, and 2.56 microF/cm(2), respectively. The mean
      specific capacitance for MCF/neo was significantly different from that for
      MCF/HER2-11 (P = 0.006) and that for MCF/HER2-18 (P = 0.007). CONCLUSIONS: ROT is
      sufficiently sensitive to detect variations in dielectric properties in breast
      cancer cell lines overexpressing p185(neu). These differences may be related to
      the morphological alterations determined by HER-2/neu overexpression.

PMID- 11839687
TI  - Molecular biology--what's in a name?

PMID- 11839686
TI  - Correspondence re: Seki et al., Diagnosis of pancreatic adenocarcinoma by
      detection of human telomerase reverse transcriptase messenger RNA in pancreatic
      juice with sample qualification. Clin. Cancer Res., 7: 1976-1981, 2001.

PMID- 11839685
TI  - Modulation of the c-Met/hepatocyte growth factor pathway in small cell lung
      cancer.
AB  - The c-Met receptor tyrosine kinase and its ligand HGF (hepatocyte growth factor)
      have been shown to be involved in angiogenesis, cellular motility, growth,
      invasion, and differentiation. The role of c-Met/HGF axis in small cell lung
      cancer (SCLC) has not been reported previously. We have determined the expression
      of p170(c-Met) precursor and p140(c-Met) beta-chain in seven SCLC cell lines by
      immunoblotting. We used the SCLC cell line H69, which expressed an abundant
      amount of c-Met to study the function and downstream effects of c-Met activation.
      Stimulation of H69 cells with HGF (40 ng/ml, 6-h stimulation) significantly
      altered cell motility of the SCLC cells with increased formation of filopodia and
      membrane ruffling, characterized as membrane blebbing, as well as increased
      migration of the cellular clusters were seen. We have further studied the signal
      transduction pathways of HGF/c-Met in the H69 cell line. The stimulation of H69
      with HGF (40 ng/ml, >24 h, maximal at 1 h) increased the amount of reactive
      oxygen species formed by 34%. HGF stimulation (40 ng/ml, 7.5-min stimulation) of
      H69 cells showed increased tyrosine phosphorylated bands identified at M(r)
      68,000, 120,000-140,000, and 200,000. Some of these tyrosine-phosphorylated bands
      were identified as the focal adhesion proteins paxillin, FAK, PYK2, and the c-Met
      receptor itself. Phospho-specific antibodies show that tyrosines at amino acid
      (a.a.) 31 of paxillin, and autophosphorylation sites at a.a. 397 of p125FAK, and
      a.a. 402 of PYK2 are phosphorylated in response to HGF/c-Met signaling. We also
      demonstrate that the Hsp90 inhibitor geldanamycin, which also affects c-Met,
      reduced the growth and viability of four of four SCLC cell lines by 25% to 85%,
      over a 72-h time period. Geldanamycin caused apoptosis of SCLC cells, as well as
      led to increased levels of Hsp70 but not Hsp90. These results demonstrate that c
      Met/HGF pathway is functional in SCLC, and it would be useful to target this
      pathway toward novel therapy.

PMID- 11839688
TI  - Not every truth is good. The dangers of publishing knowledge about potential
      bioweapons.

PMID- 11839689
TI  - Still waiting for the end. The promise of genomics and proteomics for autoimmune
      diseases.

PMID- 11839690
TI  - Experiments in research policy. Iceland, with its free-market approach to funding
      basic research in the natural sciences, may be an interesting testing ground for
      EU research policies.

PMID- 11839694
TI  - Plants, genes and ions. Workshop on the molecular basis of ionic homeostasis and
      salt tolerance in plants.

PMID- 11839691
TI  - Waging war on the economy. The possible threat of a bioterrorist attack against
      agriculture.

PMID- 11839695
TI  - Regulating the regulators. Conference on protein phosphorylation and protein
      phosphatases.

PMID- 11839696
TI  - Looking at nuclear receptors from the heights of Erice. Workshop on nuclear
      receptor structure and function.

PMID- 11839697
TI  - Cell-nonautonomous function of the retinoblastoma tumour suppressor protein: new
      interpretations of old phenotypes.
AB  - Loss of the retinoblastoma protein (pRb) induces a cell-nonautonomous defect in
      both erythroid and neuronal differentiation. It has previously been thought that
      this reflects a requirement for pRb function in cells that normally support
      erythropoiesis and neurogenesis, rather than in the erythrocytes or neurons
      themselves. However, recent studies have challenged this interpretation, and it
      appears that erythrocytes and neurons themselves have the intrinsic requirement
      for pRb function. This requirement can be bypassed by signals supplied by wild
      type erythroid or neuronal cells. The existence of such a signalling mechanism
      has implications not only in understanding pRb function but also in the
      interpretation of other cell-nonautonomous phenotypes.

PMID- 11839698
TI  - Protein disulfide isomerases exploit synergy between catalytic and specific
      binding domains.
AB  - Protein disulfide isomerases (PDIs) catalyse the formation of native disulfide
      bonds in protein folding pathways. The key steps involve disulfide formation and
      isomerization in compact folding intermediates. The high-resolution structures of
      the a and b domains of PDI are now known, and the overall domain architecture of
      PDI and its homologues can be inferred. The isolated a and a' domains of PDI are
      good catalysts of simple thiol-disulfide interchange reactions but require
      additional domains to be effective as catalysts of the rate-limiting disulfide
      isomerizations in protein folding pathways. The b' domain of PDI has a specific
      binding site for peptides and its binding properties differ in specificity
      between members of the PDI family. A model of PDI function can be deduced in
      which the domains function synergically: the b' domain binds unstructured regions
      of polypeptide, while the a and a' domains catalyse the chemical isomerization
      steps.

PMID- 11839701
TI  - Minichromosome maintenance (MCM) proteins may be pre-cancer markers.

PMID- 11839700
TI  - Molecular testing for antibiotic resistance in Helicobacter pylori.
AB  - An estimated 7.5 million individuals in England and Wales are actively infected
      with Helicobacter pylori and hence knowledge of local resistance rates is of
      growing importance. Also, information on strain resistance following treatment
      failure is crucial in selecting an appropriate regimen as the development of
      bacterial resistance to antibiotics makes retreatment difficult. Molecular test
      methods may have an impact on improving the availability and accuracy of
      information on H pylori antimicrobial resistance to guide in the selection of
      primary as well as secondary backup treatment regimens.

PMID- 11839702
TI  - Proximal and progressive: adenomas in HNPCC.

PMID- 11839703
TI  - The chips are down for Helicobacter pylori.

PMID- 11839704
TI  - Evidence that cagA(+) Helicobacter pylori strains are disappearing more rapidly
      than cagA(-) strains.
AB  - BACKGROUND AND AIMS: The prevalence of Helicobacter pylori colonisation in
      populations in developed country has been declining, as shown by community based
      serological surveys of adults in Vammala, Finland in 1973 and 1994. In this
      study, we determined whether the proportion of subjects colonised by cagA(+) or
      cagA(-) H pylori strains has changed as the overall prevalence of H pylori(+) has
      declined. METHODS: We examined 911 sera from Vammala's study for antibodies to
      the CagA antigen of H pylori using a truncated CagA protein as the antigen in an
      ELISA and we examined the trend in acquisition and carriage of cagA(+) strains.
      RESULTS: As expected, the prevalence of carriage of both cagA(+) and cagA(-)
      strains fell between 1973 and 1994 (p<0.001). However, the prevalence of cagA(+)
      strains among those <45 years declined (34% to 8%) significantly (p<0.001) more
      than for cagA(-) strains (12% to 6%). Of 221 subjects with paired serum samples,
      12 (5.4%) changed H pylori status; the estimated seroconversion and reversion
      rates were 0.4% and 0.13% per year, respectively. Except for the few individuals
      who changed serostatus, absolute antibody levels to H pylori antigens, including
      CagA, changed little over the 21 year period. CONCLUSIONS: The decline in CagA
      seroprevalence predominantly reflects declining acquisition of cag(+) strains in
      younger subjects. In addition, these data confirm that H pylori acquisition
      chiefly occurs during childhood but continues to occur during adulthood, albeit
      at low rates, in developed countries.

PMID- 11839705
TI  - Development of antigen induced colitis in SCID mice reconstituted with spleen
      derived memory type CD4(+) CD45RB(+) T cells.
AB  - BACKGROUND AND AIMS: Enteric bacterial and/or food antigens may be crucial in the
      development of colitis but little is known of the exact mechanism of antigen
      specific reactions in this condition. The aim of this study was to determine
      whether systemically primed antigen specific CD4(+) T cells containing both
      CD45RB(high) and CD45RB(low) populations participate as a pathogenic subset that
      in turn leads to inflammatory reactions selectively in the large intestine.
      METHODS: SCID mice were reconstituted with splenic CD4(+) CD45RB(+) T cells or
      CD4(+) CD45RB(low) T cells isolated from donor mice systemically primed with
      ovalbumin (OVA) plus CFA. The reconstituted mice were then fed OVA for several
      weeks. RESULTS: Reconstitution of SCID mice with OVA primed splenic CD4(+) T
      cells, containing populations of CD45RB(high) and CD45RB(low), resulted in the
      development of colitis by 4-5 weeks following repeated administration of oral
      OVA. Histopathological study revealed thickened wall, inflammatory cell
      infiltration, crypt elongation, and loss of goblet cells in the large intestine.
      The CD4(+) CD45RB(low) population of cells extracted from the affected large
      intestine secreted high levels of interferon gamma (IFN-gamma) and tumour
      necrosis factor alpha (TNF-alpha) at the protein and mRNA levels. Administration
      of neutralising antibodies to TNF-alpha, but not to IFN-gamma, prevented the
      development of colitis. Furthermore, adoptive transfer with OVA primed splenic
      CD4(+) CD45RB(low) T cells evoked severe colitis. CONCLUSIONS: These results
      demonstrate that systemically primed activated/memory CD4(+) CD45RB(low) T cells
      can mediate the development of specific antigen induced colitis in SCID mice, and
      also that TNF-alpha is critical in the induction of this type of colitis. Our
      results contrast with those from studies in some colitis models in which
      CD45RB(low) T cells appeared to prevent colitis through secretion of
      immunosuppressive cytokines.

PMID- 11839706
TI  - Augmented increase in tight junction permeability by luminal stimuli in the non
      inflamed ileum of Crohn's disease.
AB  - BACKGROUND: Crohn's disease is associated with deranged intestinal permeability
      in vivo, suggesting dysfunction of tight junctions. The luminal contents are
      important for development of neoinflammation following resection. Regulation of
      tight junctions by luminal factors has not previously been studied in Crohn's
      disease. AIMS: The aim of the study was to investigate the effects of a luminal
      stimulus, known to affect tight junctions, on the distal ileum in patients with
      Crohn's disease. PATIENTS: Surgical specimens from the distal ileum of patients
      with Crohn's disease (n=12) were studied, and ileal specimens from colon cancer
      patients (n=13) served as controls. METHODS: Mucosal permeability to 51Cr-EDTA
      and electrical resistance were studied in Ussing chambers during luminal exposure
      to sodium caprate (a constituent of milk fat, affecting tight junctions) or to
      buffer only. The mechanisms involved were studied by mucosal ATP levels, and by
      electron and confocal microscopy. RESULTS: Baseline permeability was the same in
      non-inflamed ileum of Crohn's disease and controls. Sodium caprate induced a
      rapid increase in paracellular permeability--that is, increased permeation of
      51Cr-EDTA and decreased electrical resistance--which was more pronounced in non
      inflamed ileum of Crohn's disease, and electron microscopy showed dilatations
      within the tight junctions. Moreover, sodium caprate induced disassembly of
      perijunctional filamentous actin was more pronounced in Crohn's disease mucosa.
      Mucosal permeability changes were accompanied by mitochondrial swelling and a
      fall in epithelial ATP content, suggesting uncoupling of oxidative
      phosphorylation. CONCLUSIONS: The tight junctions in the non-inflamed distal
      ileum of Crohn's disease were more reactive to luminal stimuli, possibly mediated
      via disturbed cytoskeletal contractility. This could contribute to the
      development of mucosal neoinflammation in Crohn's disease.

PMID- 11839707
TI  - Tumour necrosis factor alpha potentiates ion secretion induced by histamine in a
      human intestinal epithelial cell line and in mouse colon: involvement of the
      phospholipase D pathway.
AB  - BACKGROUND AND AIMS: Patients suffering from inflammatory bowel disease show
      increased levels of the mast cell products histamine and tumour necrosis factor
      alpha (TNF-alpha). Treating these patients with antibodies against TNF-alpha
      diminishes the symptoms of diarrhoea. In this study, the effect of TNF-alpha on
      ion secretion induced by the mast cell mediator histamine in HT29cl.19A cells and
      mouse distal colon was investigated and the possible second messengers involved
      were studied. METHODS: Electrophysiology of filter grown HT29cl.19A cells and
      isolated mouse distal colon was used to monitor the secretory response to
      histamine with and without prior exposure to TNF-alpha for 3-24 hours.
      Phospholipase D (PLD) activity and phosphatidic acid levels were analysed by
      32P(i) labelling of HT29cl.19A cells. RESULTS: In both experimental systems TNF
      alpha was found to potentiate ion secretion induced by histamine. Phospholipid
      analysis of HT29cl.19A cells revealed that histamine activates the PLD pathway.
      Furthermore, TNF-alpha pretreated cells were found to have decreased phosphatidic
      acid levels, the intermediate product of the PLD pathway, which indicates
      upregulation of the enzyme phosphatidic acid phosphatase. CONCLUSIONS: The mast
      cell products TNF-alpha and histamine synergistically stimulate ion secretion in
      intestinal epithelium via upregulation of the PLD pathway.

PMID- 11839708
TI  - Prediction of therapeutic failure after adrenaline injection plus heater probe
      treatment in patients with bleeding peptic ulcer.
AB  - BACKGROUND: Continued or recurrent bleeding after endoscopic treatment for
      bleeding ulcer is a major adverse prognostic factor. Identification of such
      ulcers may allow for alternate treatments. AIM: To determine factors predicting
      treatment failure with combined adrenaline injection and heater probe
      thermocoagulation. METHODS: Consecutive patients with bleeding peptic ulcers who
      received endoscopic therapy between January 1995 and March 1998 were studied.
      Data on clinical presentation, endoscopic findings, and treatment outcomes were
      collected prospectively. Multiple logistic regression analysis was used to
      identify independent risk factors for treatment failure. RESULTS: During the
      study period, 3386 patients were admitted with bleeding peptic ulcers: 1144 (796
      men, 348 women) with a mean age of 62.5 (SD 17.6) years required endoscopic
      treatment. There were 666 duodenal ulcers (58.2%), 425 gastric ulcers (37.2%),
      and 53 anastomotic ulcers (4.6%). Initial haemostasis was successful in 1128
      patients (98.6%). Among them, 94 (8.2%) rebled in a median time of 48 hours
      (range 3-480). Overall failure rate was 9.6%. Mortality rate was 5% (57/1144).
      Multiple logistic regression analysis revealed that hypotension (odds ratio (OR)
      2.21, 95% confidence interval (CI) 1.40-3.48), haemoglobin level less that 10
      g/dl (OR 1.87, 95% CI 1.18-2.96), fresh blood in the stomach (OR 2.15, 95% CI
      1.40-3.31), ulcer with active bleeding (OR 1.65, 95% CI 1.07-2.56), and large
      ulcers (OR 1.80, 95% CI 1.15-2.83) were independent factors predicting
      rebleeding. CONCLUSIONS: Larger ulcers with severe bleeding at presentation
      predict failure of endoscopic therapy.

PMID- 11839709
TI  - Endoscopic transpapillary bile duct biopsy with the combination of intraductal
      ultrasonography in the diagnosis of biliary strictures.
AB  - BACKGROUND: When endoscopic retrograde cholangiopancreatography (ERCP) guided
      bile duct biopsy fails to demonstrate malignancy, it remains unclear how to
      manage patients with presumably malignant strictures. AIMS: To evaluate the value
      of intraductal ultrasonography (IDUS) when bile duct biopsy is negative. METHODS:
      Sixty two patients with strictures of the bile duct were studied prospectively.
      During ERCP, IDUS was performed using an ultrasonic probe (diameter 2.0 mm;
      frequency 20 MHz). Following IDUS, a bile duct biopsy was performed using forceps
      (diameter 1.8 mm). The IDUS images of the tumour were classified as polypoid
      lesions, localised wall thickening, intraductal sessile tumours, sessile tumour
      outside of the bile duct, or absence of apparent lesion. The bile duct wall
      structures at the site of the tumour as well as the maximum diameter of the
      tumour were also analysed. The IDUS findings were compared with the histological
      findings or clinical course. RESULTS: When the IDUS images showed a polypoid
      lesion (n=19), localised wall thickening (n=8), intraductal sessile tumour
      (n=13), and sessile tumour outside of the bile duct (n = 20), the sensitivities
      of the biopsy were 80%, 50%, 92%, and 53%, respectively. Multiple regression
      analysis showed that the presence of sessile tumour (intraductal or outside of
      the bile duct: p<0.05), tumour size greater than 10.0 mm (p<0.001), and
      interrupted wall structure (p<0.05) were independent variables that predicted
      malignancy. CONCLUSION: When biopsy fails to demonstrate evidence of malignancy,
      the presence of sessile tumour (intraductal or outside of the bile duct), tumour
      size greater than 10.0 mm, and interrupted wall structure on IDUS images are
      factors that can predict malignancy.

PMID- 11839710
TI  - No harm from five year ingestion of oats in coeliac disease.
AB  - BACKGROUND: Six to 12 months of ingestion of moderate amounts of oats does not
      have a harmful effect in adult patients with coeliac disease. As the safety of
      long term intake of oats in coeliac patients is not known, we continued our
      previous 6-12 month study for five years. AIM: To assess the safety of long term
      ingestion of oats in the diet of coeliac patients. PATIENTS: In our previous
      study, the effects of a gluten free diet and a gluten free diet including oats
      were compared in a randomised trial involving 92 adult patients with coeliac
      disease (45 in the oats group, 47 in the control group). After the initial phase
      of 6-12 months, patients in the oats group were allowed to eat oats freely in
      conjunction with an otherwise gluten free diet. After five years, 35 patients in
      the original oats group (23 still on an oats diet) and 28 in the control group on
      a conventional gluten free diet were examined. METHODS: Clinical and nutritional
      assessment, duodenal biopsies for conventional histopathology and
      histomorphometry, and measurement of antiendomysial, antireticulin, and
      antigliadin antibodies. RESULTS: There were no significant differences between
      controls and those patients consuming oats with respect to duodenal villous
      architecture, inflammatory cell infiltration of the duodenal mucosa, or antibody
      titres after five years of follow up. In both groups histological and
      histomorphometric indexes improved equally with time. CONCLUSIONS: This study
      provides the first evidence of the long term safety of oats as part of a coeliac
      diet in adult patients with coeliac disease. It also appears that the majority of
      coeliac patients prefer oats in their diet.

PMID- 11839711
TI  - MHC class I chain related gene A (MICA) modulates the development of coeliac
      disease in patients with the high risk heterodimer DQA1*0501/DQB1*0201.
AB  - BACKGROUND AND AIMS: Coeliac disease (CD) is an enteropathic disorder
      characterised by a strong association with major histocompatibility complex (MHC)
      heterodimer HLA-DQ2. It has been suggested that other HLA class I genes in
      combination with DQ may also contribute to CD susceptibility. The aim of this
      study was to investigate whether other candidate genes modify the risk of
      developing different clinical forms of CD. PATIENTS AND METHODS: We studied 133
      Spanish coeliac patients, divided according to their clinical presentation into
      typical and atypical groups, and 116 healthy controls. All were typed by
      polymerase chain reaction-sequence specific primers (PCR-SSP) at HLA-B, DRB1,
      DQA1, and DQB1 loci and for exon 5 of the MHC class I chain related gene A
      (MICA). RESULTS: No differences were found in the frequency of the
      DQA1*0501/DQB1*0201 heterodimer in either group. The risk of typical CD was
      significantly associated with the DR7/DQ2 haplotype (p(c)=0.02, odds ratio
      (OR)=3.4, ethiological fraction (EF)=0.4). Extended haplotype (EH) 8.1
      (B8/DR3/DQ2) was found to be overrepresented in the atypical form compared with
      the typical form (p(c)=0.001, OR=4.19, EF=0.56). The trinucleotide repeat
      polymorphism MICA-A5.1 was found to be increased in the atypical group of
      patients compared with the typical group (p(c)=0.00006, OR=8.63, EF=0.81). This
      association was independent of linkage disequilibrium with EH8.1 as this was also
      found to be increased in EH8.1 negative atypical patients compared with the
      typical group (p(c)=0.004, OR=6.66, EF=0.56). CONCLUSIONS: Our results showed
      that the risk of developing typical forms of CD was associated with DR7/DQ2
      haplotype, and the presence of B8/DR3/DQ2 was significantly increased in atypical
      patients. In these, the MICA-A5.1 allele confers an additive effect to the
      DR3/DQ2 haplotype that may modulate the development of CD.

PMID- 11839713
TI  - Acute restraint stress activates functional NK1 receptor in the colon of female
      rats: involvement of steroids.
AB  - BACKGROUND AND AIMS: Psychological factors have been implicated in the aetiology
      of irritable bowel syndrome characterised by intestinal altered motility and
      visceral hypersensitivity. Similar disorders have been found in rats under
      stressful conditions. The role of tachykinins in bowel dysfunctions caused by
      stress is not fully documented. Therefore, we investigated the influence of
      stress on NK1 receptor activation at the colonic level in female rats. METHODS:
      The stress procedure used consisted of two hours of partial restraint. Histamine
      release was measured from colonic samples of control and stressed animals and the
      effect of SR140333, a NK1 receptor antagonist, on substance P induced histamine
      release was determined. Involvement of steroids has been evaluated in this
      response. RESULTS: NK1 receptor antagonist was found to inhibit substance P
      induced histamine release in samples from stressed female rats but not in samples
      from control animals. Previous treatment of female rats with RU 486 abolished
      this effect observed in stressed animals. Similarly, in samples from stressed
      female rats previously ovariectomised, SR140333 failed to inhibit substance P
      induced histamine release but previous treatment with both progesterone and
      oestrogen restored its effect. CONCLUSIONS: Stress induces NK1 receptor
      activation in the colon, and ovarian steroids are involved in this response.

PMID- 11839712
TI  - Effects of glucagon-like peptide-1(7-36)amide on motility and sensation of the
      proximal stomach in humans.
AB  - BACKGROUND: Glucagon-like peptide-1(7-36)amide (GLP-1) retards gastric emptying,
      reduces food intake, and inhibits antroduodenal and stimulates pyloric motility.
      AIMS: To assess the effects of synthetic GLP-1 on fundus tone and volume waves,
      gastric compliance, and perception of gastric distension. SUBJECTS: Eleven
      healthy male volunteers. METHODS: Background infusions were saline, or GLP-1 at
      0.3 or 0.9 pmol/ kg/min on separate days in random order. Interdigestive fundus
      motility was recorded by barostat (maximum capacity of intragastric bag 1200 ml)
      during basal and peptide periods of 60 minutes each. Thereafter stepwise isobaric
      distensions were performed with ongoing peptide infusion, and gastric sensation
      was scored. RESULTS: Low and high loads of GLP-1 induced physiological and
      supraphysiological plasma immunoreactivities, respectively. GLP-1 dose
      dependently diminished fundus tone (162.9 (15.0) and 259.5 (17.2) v 121.1 (6.0)
      ml with saline; p<0.0001). It greatly reduced volume waves and total volume
      displaced by these events (p<0.0001). Gastric compliance derived from isobaric
      distension rose in a dose related manner (42.6 (5.5) and 63.6 (7.7) v 27.0 (3.5)
      ml/mm Hg; p=0.0004) with a concomitant reduction of the pressure at half maximum
      bag volume (6.4 (0.4) and 5.5 (0.4) v 7.2 (0.1) mm Hg; p<0.0001). GLP-1 did not
      change perception of isobaric distension but reduced the perception score related
      to corresponding bag volume (p<0.0001). CONCLUSIONS: GLP-1 is a candidate
      physiological inhibitory regulator of fundus motility. It allows the stomach to
      afford a larger volume without increase in sensation.

PMID- 11839714
TI  - Increased smooth muscle contractility of intestine in the genetic null of the
      endothelin ETB receptor: a rat model for long segment Hirschsprung's disease.
AB  - BACKGROUND AND AIMS: The endothelin ETB receptor null rat (ETB(-/-)R) has an
      intestinal segment without ganglia, and this rat is characterised by intestinal
      obstruction similar to that observed in human Hirschsprung's disease. In the
      present study, we have examined the myogenic mechanism responsible for
      obstruction in the ETB(-/-)R. RESULTS: The ETB(-/-)R had an enlarged belly and
      the average lifespan was 18.1 days. The bowel from the rectum to the lower part
      of the small ileum was constricted whereas the upper region was dilated with
      faecal stasis and thus presented as megaileum. The constricted muscle segments
      without ganglia had a greater increase in absolute force when stimulated by
      carbachol, high K+, and endothelin-1 compared with that of normal siblings. In
      contrast, in the dilated part with ganglia, the absolute contractile force due to
      these stimulants in the ETB(-/-)R was not different from that in the ETB(+/+)R.
      Such a functional hypertrophy of the musculature was observed in parts of the
      colon, caecum, and distal ileum without ganglia but not in the part of the
      proximal ileum and jejunum with ganglia. Morphological study demonstrated that
      the thickness of the circular and longitudinal muscle layers was greater in the
      constricted part of the intestine in the ETB(-/-)R, and these changes were
      associated with an increase in the number of smooth muscle cells. CONCLUSIONS:
      Our findings suggest that both increased contractility of smooth muscle and
      increased thickness of the intestinal muscular wall may contribute to the
      intestinal obstruction in the ETB(-/-)R.

PMID- 11839715
TI  - Associated changes of lipid peroxidation and transforming growth factor beta1
      levels in human colon cancer during tumour progression.
AB  - BACKGROUND: During neoplastic progression, alterations in transforming growth
      factor beta1 (TGF-beta1) dependent control of cell growth may be an important
      mechanism of selective proliferation of transformed cellular clones. Defective
      regulation of TGF-beta1 receptors has been reported to occur in a number of human
      malignant tumours while little is known of the actual levels of this growth
      inhibitory cytokine in cancer. On the basis of the demonstrated ability of major
      lipid peroxidation products such as 4-hydroxynonenal to modulate TGF-beta1
      expression and synthesis, we speculated that decreased lipid oxidation, as
      frequently observed in neoplastic tissues, would contribute to the selective
      promotion of tumour growth through decreased expression of the cytokine within
      the tumour mass. AIMS: To seek a possible association between steady state levels
      of major aldehydic end products of lipid peroxidation and TGF-beta1 content in
      human colon cancer at different stages of growth. PATIENTS AND METHODS: Tissue
      biopsies from 15 adult patients with colon adenocarcinoma of different TNM and G
      stagings were compared with regard to lipid peroxidation aldehydes and net TGF
      beta1 levels. For a more comprehensive analysis, cytokine type I and II receptors
      were measured in tumour biopsies. In one set of experiments, to support the
      conclusions, the apoptotic effect of TGF-beta1 was evaluated in a human colon
      cancer cell line, CaCo-2, retaining receptor changes consistent with those
      observed in cancer patients. RESULTS: With the exception of two extremely
      advanced cases (T4/G3) in which tissue levels of lipid peroxidation were within
      the normal range, 4-hydroxynonenal was significantly decreased in all other
      cancer specimens. Consistent with lipid peroxidation levels, TGF-beta1 protein
      was markedly decreased or even negligible compared with the corresponding normal
      tissue surrounding the tumour in all tested biopsies except for the two T4/G3
      colon cancers in which cytokine content was again within the normal range. As
      regards TGF-beta1 receptors, both in tumour sections and CaCo-2 cells,
      downregulation was greater for TGF-beta1 receptor I than for receptor II. Of
      note, in CaCo-2 cells, incubation with appropriate doses of TGF-beta1 led to
      marked nuclear fragmentation and apoptosis. CONCLUSIONS: Evasion of human colon
      cancer cells from TGF-beta1 mediated growth inhibition appears to be due not only
      to downregulation of TGF-beta1 receptors, which is inconsistent and unrelated to
      cancer development, but also to the constant low concentration of this cytokine
      in the tumour mass. The associated levels of lipid peroxidation aldehydes, much
      lower than in control tissue, probably represent a lower stimulus for TGF-beta1
      production in the neoplastic area and thus a favourable condition for neoplastic
      progression.

PMID- 11839716
TI  - Epidemiological differences between adenocarcinoma of the oesophagus and
      adenocarcinoma of the gastric cardia in the USA.
AB  - BACKGROUND AND AIMS: It has been suggested that gastric cardia adenocarcinoma
      (GCA) is a distinct entity from oesophageal adenocarcinoma (OA). We examined
      several epidemiological features of GCA and OA in the USA to elucidate
      differences/similarities between these malignancies. METHODS: Using the database
      of Surveillance, Epidemiology, and End Results (SEER) program, we examined
      incidence rates for temporal changes, and ethnic and age distributions, and
      performed birth cohort analyses for cases with morphologically and histologically
      confirmed OA or GCA. RESULTS: The age adjusted incidence rates of OA rose
      progressively, reaching 1.8 per 100 000 (95% confidence interval 1.7-1.9) during
      1987-1991 and 2.5 per 100 000 (2.3-2.6) during 1992-1996. In 1992-1996, Whites
      were affected five times more than Blacks, and men eight times more than women. A
      significant increase in incidence occurred among younger persons aged 45-65
      years. Irrespective of age, OA was characterised by higher incidence rates among
      more recent birth cohorts: a 40% increase in incidence for each five year
      increase in the date of birth--a "birth cohort effect". On the other hand, the
      incidence rates of GCA reached their highest level of 3.3 per 100 000 (3.2-3.4)
      in 1987-1991 and subsequently declined during 1992-1996 to 3.1 per 100 000 (3.0
      3.3). Whites were affected twice more than blacks and men five times more than
      women. Most patients with GCA were older than 60 years with no increase among
      younger persons and no birth cohort effect (p=0.99). CONCLUSION: Several
      significant epidemiological differences exist between OA and GCA. These
      differences suggest that these two malignancies are separate entities with
      different risk factors.

PMID- 11839717
TI  - Aberrant expression of minichromosome maintenance proteins 2 and 5, and Ki-67 in
      dysplastic squamous oesophageal epithelium and Barrett's mucosa.
AB  - BACKGROUND: Minichromosome maintenance (Mcm) proteins are essential for
      eukaryotic DNA replication, and their expression implies potential for cell
      proliferation. Expression is dysregulated in dysplastic states but data for
      oesophageal squamous mucosa and Barrett's mucosa have not been published. AIM: To
      test the hypothesis that Mcm proteins are downregulated together with the
      proliferation marker Ki-67 in differentiating epithelial compartments of non
      dysplastic squamous and Barrett's epithelium, and that this process does not
      occur in dysplastic mucosae. METHODS AND CASES: Forty five patients with
      Barrett's oesophagus included 20 with glandular dysplasia (10 low grade, eight
      high grade, two both, and four with invasive adenocarcinoma). Twenty five other
      patients included 12 with oesophageal squamous dysplasia (three low grade, six
      high grade, three both, and four with invasive squamous carcinoma). Formalin
      fixed paraffin embedded tissue sections from biopsy series and resections were
      immunostained using antibodies to Mcm2, Mcm5, and Ki-67. Percentage of nuclei
      positive for Mcm2, Mcm5, and Ki-67 was estimated and scored from 0 to 6 as: 0,
      none +; 1, <10%+; 2, 10-30%+; 3, 30-70%+; 4, 70-90%+; 5, >90%+; 6, all+. Four
      separate epithelial strata were scored: in squamous epithelium the basal layer
      and thirds to the surface, in Barrett's mucosa the luminal surface, upper and
      lower crypt, and deep glands. RESULTS: In non-dysplastic squamous epithelium and
      Barrett's mucosa, high level expression of Mcm2, Mcm5, and Ki-67 proteins was
      largely confined to the proliferative compartments and downregulated in
      differentiated compartments. Expression persisted up to the mucosal surface in
      dysplastic squamous epithelium and Barrett's mucosa. CONCLUSIONS: Persistent
      expression of Mcm2, Mcm5, and Ki-67 proteins in luminal compartments of
      dysplastic oesophageal squamous epithelium and dysplastic Barrett's mucosa may be
      diagnostic markers and imply disruption of cell cycle control and differentiation
      in these dysplastic epithelia.

PMID- 11839718
TI  - The long term results of endoscopic surveillance of premalignant gastric lesions.
AB  - BACKGROUND: A large proportion of patients attending open access endoscopy have
      histological and gross pathological findings that are potentially premalignant.
      The proportion of these patients who go on to develop malignancies and the
      timescale over which this occurs are uncertain. AIMS: This study aims to discover
      the incidence of gastric cancers in this "high risk" group and to examine the
      potential for their early diagnosis and treatment. PATIENTS: A total of 1753
      patients attended open access endoscopy. From these, 166 patients with dysplasia,
      intestinal metaplasia, atrophic gastritis, foveolar hyperplasia, regenerative
      changes, polyps, or ulcers who agreed to undergo annual surveillance endoscopy
      were studied. METHODS: Patients were endoscoped annually. Additionally, patients
      with ulcers were re-examined at two monthly intervals until ulcer healing.
      Cancers detected were treated by gastrectomy. RESULTS: Twenty two of 1753
      patients attending open access endoscopy had gastric cancer (1.3%). In the study
      population, 14 cancers were detected over 10 years (8.4 %). These were of an
      earlier stage than those detected at open access (stage I and II 67% v 23%;
      p<0.05) and five year survival was significantly higher (50% v 10%; p=0.006). In
      atrophic gastritis and intestinal metaplasia the risk of malignancy was 11%.
      CONCLUSIONS: In patients with atrophic gastritis or intestinal metaplasia, annual
      surveillance can detect most new tumours at an early stage with a major
      improvement in survival. Potential benefits of such a surveillance programme are
      large and warrant further investigation in a multicentre randomised controlled
      trial.

PMID- 11839719
TI  - Proximal adenomas in hereditary non-polyposis colorectal cancer are prone to
      rapid malignant transformation.
AB  - BACKGROUND: Hereditary non-polyposis colorectal cancer (HNPCC) is thought to
      arise from adenomas. HNPCC mostly occurs in the proximal colon. We investigated
      whether this proximal preponderance is due to a proximal preponderance of
      adenomas or (also) differences in transformation rates from adenomas to cancer
      between the distal and proximal colon. METHODS: A total of 100 HNPCC adenomas
      were evaluated and compared with 152 sporadic adenomas for location, size, and
      dysplasia. Twenty five adenomas from patients with a known mismatch repair (MMR)
      gene mutation were stained for expression of MLH1 and MSH2. RESULTS: HNPCC
      adenomas were more often located proximally (50% v 26%; p=0.018) and were smaller
      in comparison with sporadic adenomas. They were similarly dysplastic. However,
      all proximal HNPCC adenomas > or =5 mm were highly dysplastic compared with 17%
      of the larger proximal sporadic polyps (p<0.001). They were also more often
      highly dysplastic than larger distal HNPCC adenomas (p<0.001). Small HNPCC
      adenomas were, except for their location, not different from sporadic adenomas.
      Fifteen of the 25 "known mutation" adenomas showed loss of expression of either
      MLH1 or MSH2. The 10 adenomas with expression were all small with low grade
      dysplasia. CONCLUSION: HNPCC adenomas are located mainly in the proximal colon.
      The progression to high grade dysplasia is more common in proximal than distal
      HNPCC adenomas, indicating a faster transformation rate from early adenoma to
      cancer in the proximal colon. MMR gene malfunction probably does not initiate
      adenoma development but is present at a very early stage of tumorigenesis and
      heralds the development of high grade dysplasia.

PMID- 11839720
TI  - Subcutaneous or intrahepatic injection of suicide gene modified tumour cells
      induces a systemic antitumour response in a metastatic model of colon carcinoma
      in rats.
AB  - BACKGROUND: Suicide gene therapy consists of the transfer into tumour cells of a
      "suicide" gene that can convert a non-toxic compound into a lethal drug.
      Expression of the cytosine deaminase gene leads to the conversion of the non
      toxic compound 5-fluorocytosine to 5-fluorouracil. We have recently shown that
      "suicide cell based vaccination" consisting of intrahepatic injection of cytosine
      deaminase expressing colon cancer cells followed by 5-fluorocytosine treatment
      induces regression of a distant wild-type liver tumour in rats. AIMS: This study
      was conducted to test if (i) a distant bystander effect on a liver tumour can be
      induced after subcutaneous suicide cell based vaccination and (ii) suicide cell
      based vaccination is efficient in limiting tumour dissemination to extrahepatic
      compartments. METHODS: An aggressive variant of rat colon carcinoma cells was
      selected after successive passages in vitro. Rats carrying an experimental liver
      "metastasis" generated by injection of these cells were vaccinated by subcapsular
      or subcutaneous injection of cytosine deaminase expressing cells followed by 5
      fluorocytosine treatment. RESULTS: Subcutaneous and subcapsular vaccination
      induced 70% regression in the median volume of the pre-established liver tumour
      (p=0.001) and abolished tumour dissemination compared with control animals.
      CONCLUSIONS: This study has compared for the first time the efficiency of
      subcutaneous and intrahepatic suicide cell based vaccination in a metastatic
      colorectal carcinoma model in rats. The results indicate that both modes of
      vaccination are equally efficient in inducing a systemic antitumour response,
      suggesting that this strategy is a powerful approach against the development and
      dissemination of metastatic colon carcinoma.

PMID- 11839721
TI  - Galectin-8 expression decreases in cancer compared with normal and dysplastic
      human colon tissue and acts significantly on human colon cancer cell migration as
      a suppressor.
AB  - BACKGROUND AND AIMS: Galectins are beta-galactoside binding proteins. This
      ability may have a bearing on cell adhesion and migration/proliferation in human
      colon cancer cells. In addition to galectins-1 and -3 studied to date, other
      members of this family not investigated in detail may contribute to modulation of
      tumour cell features. This evident gap has prompted us to extend galectin
      analysis beyond the two prototypes. The present study deals with the quantitative
      determination of immunohistochemical expression of galectin-8 in normal, benign,
      and malignant human colon tissue samples and in four human colon cancer models
      (HCT-15, LoVo, CoLo201, and DLD-1) maintained both in vitro as permanent cell
      lines and in vivo as nude mice xenografts. The role of galectin-8 (and its
      neutralising antibody) in cell migration was investigated in HCT-15, LoVo,
      CoLo201, and DLD-1 cell lines. METHODS: Immunohistochemical expression of
      galectin-8 and its overall ability to bind to sugar ligands (revealed
      glycohistochemically by means of biotinylated histochemically inert carrier
      bovine serum albumin with alpha- and beta-D-galactose, alpha-D-glucose, and
      lactose derivatives as ligands) were quantitatively determined using computer
      assisted microscopy. The presence of galectin-8 mRNA in the four human colon
      cancer cell lines was examined by reverse transcriptase-polymerase chain
      reaction. In vitro, cellular localisation of exogenously added galectin-8 in the
      culture media of these colon cancer cells was visualised by fluorescence
      microscopy. In vitro galectin-8 mediated effects (and the influence of its
      neutralising antibody) on migration levels of living HCT-15, LoVo, CoLo201, and
      DLD-1 cells were quantitatively determined by computer assisted phase contrast
      microscopy. RESULTS: A marked decrease in immunohistochemical expression of
      galectin-8 occurred with malignancy development in human colon tissue. Malignant
      colon tissue exhibited a significantly lower galectin-8 level than normal or
      benign tissue colon cancers; those with extensive invasion capacities (T3
      4/N+/M+) harboured significantly less galectin-8 than colon cancers with
      localised invasion capacities (T1-2/N0/M0). The four experimental models (HCT-15,
      LoVo, CoLo201, and DLD-1) had more intense galectin-8 dependent staining in vitro
      than in vivo. Grafting the four experimental human colon cancer models onto nude
      mice enabled us to show that the immunohistochemical expression of galectin-8 was
      inversely related to tumour growth rate. In vitro, galectin-8 reduced the
      migration rate of only those human experimental models (HCT-15 and CoLo201) that
      exhibited the lowest growth rate in vivo. CONCLUSIONS: Expression of galectin-8
      correlated with malignancy development, with suppressor activity, as shown by
      analysis of clinical samples and xenografts. In vitro, only the two models with
      low growth rates were sensitive to the inhibitory potential of this galectin.
      Future investigations in this field should involve fingerprinting of these newly
      detected galectins, transcending the common focus on galectins-1 and -3.

PMID- 11839722
TI  - Serrated adenoma in familial adenomatous polyposis: relation to germline APC gene
      mutation.
AB  - BACKGROUND: Serrated adenoma is a precursor of colorectal cancer. AIM: To clarify
      possible genotype-phenotype correlations of serrated adenomas in familial
      adenomatous polyposis (FAP). PATIENTS: Eleven patients from eight families with
      FAP. METHODS: We performed total colonoscopy with multiple biopsies in patients.
      Neoplasia with a serrated glandular structure was regarded as a serrated adenoma.
      In each patient, germline mutations of the APC gene were determined. Colonic
      phenotype was compared with germline mutations of the APC gene. RESULTS: Serrated
      adenomas were found in three patients. These patients had macroscopic polyps <100
      in number. Pedigrees with serrated adenomas had the truncating germline APC
      mutation at codon 161, 332, or 1556 while in the other pedigrees mutations were
      found between codons 554 and 1324. CONCLUSIONS: In FAP, serrated adenoma may be a
      phenotype characteristic of the attenuated form.

PMID- 11839723
TI  - Pathogenicity of missense and splice site mutations in hMSH2 and hMLH1 mismatch
      repair genes: implications for genetic testing.
AB  - BACKGROUND: In hereditary non-polyposis colorectal cancer, over 90% of the
      identified mutations are in two genes, hMSH2 and hMLH1. A large proportion of the
      mutations detected in these genes are of the missense type which may be either
      deleterious mutations or harmless polymorphisms. AIM: To investigate whether nine
      missense and one splice site mutation of hMLH1 and hMSH2, in 10 kindreds with a
      familial history of colorectal cancer or young age of onset, could be interpreted
      as pathogenic. METHODS: Clinical and genetic characteristics were collected: (i)
      evolutionary conservation of the codon involved; (ii) type of amino acid change;
      (iii) occurrence of mutation in healthy controls; (iv) cosegregation of mutation
      with disease phenotype; (v) functional consequences of gene variant; and (vi)
      microssatellite instability and immunoexpression of hMSH2 and hMLH1 analysis.
      RESULTS: Seven different missense and one splice site mutation were identified.
      Only 1/8 was found in the control group, 2/7 occurred in conserved residues, and
      5/7 resulted in non-conservative changes. Functional studies were available for
      only 2/8 mutations. Segregation of the missense variant with disease phenotype
      was observed in three kindreds. CONCLUSION: In the majority of families included,
      there was no definitive evidence that the missense or splice site alterations
      were causally associated with an increased risk of developing colorectal cancer.
      Until further evidence is available, these mutational events should be regarded
      and interpreted carefully and genetic diagnosis should not be offered to these
      kindreds.

PMID- 11839724
TI  - Denatured H-ferritin subunit is a major constituent of haemosiderin in the liver
      of patients with iron overload.
AB  - BACKGROUND AND AIMS: Iron is stored in hepatocytes in the form of ferritin and
      haemosiderin. There is a marked increase in iron rich haemosiderin in iron
      overloaded livers, and ferric iron in amounts exceeding the ferritin and
      haemosiderin binding capacity may promote free radical generation, causing
      cellular damage. The aim of this study was to characterise hepatic haemosiderin
      using four antibodies specific for either native or denatured H/L-ferritin
      subunits. METHODS: Ferritin and haemosiderin were prepared from the livers of
      three patients with post-transfusional iron overload. The assembled ferritin
      molecules were analysed by non-denaturing polyacrylamide gel electrophoresis
      (PAGE)-immunoblotting. Ferritin subunits in the haemosiderin fraction were
      assessed by denaturing sodium dodecyl sulphate (SDS)-PAGE-immunoblotting.
      Distribution of native and denatured ferritin subunits in hepatocytes was
      examined by immunogold electron microscopy. RESULTS: Non-denaturing PAGE
      immunoblot analyses showed that the assembled liver ferritins were recognised by
      the antibodies for native ferritins and not by those for the denatured subunits.
      Both SDS-PAGE-immunoblot and immunogold electron microscopic analyses disclosed
      that haemosiderin of iron overloaded liver reacted predominantly to the
      monoclonal antibody for the denatured H-ferritin subunit, to a lesser degree to
      that for denatured L-ferritin, and very weakly, if any, with antibodies for
      native H-ferritin or L-ferritin. CONCLUSIONS: These results suggest that in iron
      overloaded liver, haemosiderin consists predominantly of denatured H-ferritin
      subunits.

PMID- 11839725
TI  - A global emerging disease of Klebsiella pneumoniae liver abscess: is serotype K1
      an important factor for complicated endophthalmitis?
AB  - BACKGROUND AND AIMS: Over the past two decades in Taiwan, pyogenic liver abscess
      has usually been caused by a single microorganism, Klebsiella pneumoniae, and is
      frequently associated with the serious complication of endophthalmitis,
      especially in diabetic patients. However, the relationship between the clinical
      presentation and bacterial factors remains unclear. The aim of this study was to
      investigate the clinical features of patients and the serotype and ribotype of K
      pneumoniae liver abscess. METHODS: From July 1991 to June 1998, a total of 134
      cases of K pneumoniae liver abscess with 248 K pneumoniae isolates from the same
      patients were collected from two large medical centres in northern Taiwan.
      Clinical data were collected from medical records. Serotyping and ribotyping were
      performed using the countercurrent immunoelectrophoresis method and automated
      Riboprinter. RESULTS: Serotyping revealed that the most common serotypes were K1
      (63.4%) and K2 (14.2%). K1 isolates occurred at a significantly higher frequency
      (p<0.01) than all other serotypes. Among 134 patients, 105 (78.4%) had suffered
      from diabetes mellitus for 3-15 years. Fourteen patients (10.4%) had metastatic
      infection to the eye causing septic endophthalmitis. Liver aspirates, and blood
      and vitreous pus cultures yielded the same serotype of K pneumoniae in all
      patients. Among patients with septic endophthalmitis, 92.3% (13/14) were
      diabetic, and 85.7% (12/14) of the isolates belonged to serotype K1. For
      molecular typing, different degrees of genetic polymorphism among isolates with
      the same K1 serotype suggested no particular prevalence of any one strain in K
      pneumoniae liver abscess. CONCLUSION: K pneumoniae serotype K1 was significantly
      associated with liver abscess and the complication of endophthalmitis, especially
      in diabetic patients. Physicians should request an immediate report of serotyping
      and susceptibility test results simultaneously if a diagnosis of pyogenic liver
      abscess has been made so that early and appropriate management for possible
      complications will not be delayed. The use of ceftriaxone because of its higher
      concentration in the aqueous humor is suggested to decrease the chance of septic
      endophthalmitis.

PMID- 11839726
TI  - Assessment of therapeutic benefit of antiviral therapy in chronic hepatitis C: is
      hepatic venous pressure gradient a better end point?
AB  - Chronic hepatitis C is a major healthcare problem. The response to antiviral
      therapy for patients with chronic hepatitis C has previously been defined
      biochemically and by PCR. However, changes in the hepatic venous pressure
      gradient (HVPG) may be considered as an adjunctive end point for the therapeutic
      evaluation of antiviral therapy in chronic hepatitis C. It is a validated
      technique which is safe, well tolerated, well established, and reproducible.
      Serial HVPG measurements may be the best way to evaluate response to therapy in
      chronic hepatitis C.

PMID- 11839728
TI  - Hepatitis and liver dysfunction with rifampicin therapy for pruritus in primary
      biliary cirrhosis.
AB  - There is evidence to suggest that rifampicin is an effective second line therapy
      for controlling pruritus in patients with chronic cholestatic liver disease. It
      is most widely used as an antipruritic agent in the autoimmune cholestatic liver
      disease, primary biliary cirrhosis (PBC). Rifampicin has been reported as causing
      hepatitis in patients being treated for tuberculosis. Most reports of this have
      been confounded however by the concurrent use of other hepatotoxic antitubercular
      therapy. Here we report a single centre experience of the use of rifampicin in
      PBC, and describe three cases of significant hepatitis associated with rifampicin
      therapy. Two of these patients had significant impairment of liver synthetic
      function (necessitating liver transplantation in one case). These are the first
      reports of impaired hepatic synthetic function due to rifampicin monotherapy.
      Rifampicin caused significant hepatitis in 7.3% (95% confidence interval 2.5
      19.4%) of patients treated for cholestatic liver disease in our centre.

PMID- 11839727
TI  - Gut adaptation and the glucagon-like peptides.
AB  - The glucagon-like peptides GLP-1 and GLP-2 are synthesised and then released from
      enteroendocrine cells in the small and large intestine. GLP-1 promotes efficient
      nutrient assimilation while GLP-2 regulates energy absorption via effects on
      nutrient intake, gastric acid secretion and gastric emptying, nutrient
      absorption, and mucosal permeability. Preliminary human studies indicate that GLP
      2 may enhance energy absorption and reduce fluid loss in subjects with short
      bowel syndrome suggesting that GLP-2 functions as a key regulator of mucosal
      integrity, permeability, and nutrient absorption. Hence GLP-2 may be
      therapeutically useful in diseases characterised by injury or dysfunction of the
      gastrointestinal epithelium.

PMID- 11839729
TI  - Calpain inhibitor I and colonic inflammation induced by DNBS in the rat.

PMID- 11839730
TI  - A shake of the head to a wink of the anus.

PMID- 11839731
TI  - Mucosal barrier function and the commensal flora.

PMID- 11839732
TI  - v-Src SH3-enhanced interaction with focal adhesion kinase at beta 1 integrin
      containing invadopodia promotes cell invasion.
AB  - In viral Src (v-Src)-transformed cells, focal adhesion kinase (FAK) associates
      with v-Src by combined v-Src SH2 and gain-of-function v-Src SH3 domain binding to
      FAK. Here we assess the significance of the Arg-95 to Trp gain-of-function
      mutation in the v-Src SH3 domain through comparisons of Src-/- fibroblasts
      transformed with either Prague C v-Src or a point mutant (v-Src-RT) containing a
      normal (Arg-95) SH3 domain. Both v-Src isoforms exhibited equivalent kinase
      activity, enhanced Src-/- cell motility, and stimulated cell growth in both low
      serum and soft agar. The stability of a v-Src-RT.FAK signaling complex and FAK
      phosphorylation at Tyr-861 and Tyr-925 were reduced in v-Src-RT- compared with v
      Src-transformed cells. v-Src but not v-Src-RT promoted Src-/- cell invasion
      through a reconstituted Matrigel basement membrane barrier and v-Src co-localized
      with FAK and beta(1) integrin at invadopodia. In contrast, v-Src-RT exhibited a
      partial perinuclear and focal contact distribution in Src-/- cells. Adenovirus
      mediated FAK overexpression promoted v-Src-RT recruitment to invadopodia, the
      formation of a v-Src-RT.FAK signaling complex, and reversed the v-Src-RT invasion
      deficit. Adenovirus-mediated inhibition of FAK blocked v-Src-stimulated cell
      invasion. These studies establish that gain-of-function v-Src SH3 targeting
      interactions with FAK at beta(1) integrin-containing invadopodia act to stabilize
      a v-Src.FAK signaling complex promoting cell invasion.

PMID- 11839734
TI  - Proteolysis of chimeric beta-amyloid precursor proteins containing the Notch
      transmembrane domain yields amyloid beta-like peptides.
AB  - gamma-Secretase is an unusual intramembranous protease that has been reported to
      cleave the beta-amyloid precursor protein (APP) near the middle of its
      transmembrane domain (TMD) but cleave Notch near the cytoplasmic end of its TMD.
      To ascertain whether the TMD sequence of the substrate determines where gamma
      secretase cleaves and whether the region just before the TMD participates in
      recognition by the enzyme, we expressed chimeric human APP molecules containing
      either the TMD or pre-TMD regions of Notch or other transmembrane proteins. APP
      chimeras bearing either the Notch or the amyloid precursor-like protein-2 TMD
      released similar amounts of approximately 4-kDa amyloid beta-peptide (Abeta)-like
      peptides as did intact APP. Mass spectrometry revealed that the principal Abeta
      like peptide ended at residue 40, indicating cleavage at the middle of the Notch
      TMD in the chimera. Generation of Abeta-like peptides was significantly decreased
      when the APP TMD was replaced by those of SREBP-1 or human epithelial growth
      factor receptor 3. Replacement of the APP pre-TMD region (Abeta 10-28) with that
      of SREBP-1 increased generation of Abeta-like peptides, while those of human
      epithelial growth factor receptor 3 or amyloid precursor-like protein-2 decreased
      it. We conclude that gamma-secretase can cleave near the middle of the Notch TMD,
      that Abeta-like peptides may arise during Notch processing, and that the pre-TMD
      sequence of the substrate influences recognition or binding by the enzyme.

PMID- 11839735
TI  - Secretion of antithrombin is converted from nonpolarized to apical by exchanging
      its amino terminus for that of apically secreted family members.
AB  - The three members of the serpin family, corticosteroid binding globulin, alpha1
      antitrypsin, and C1 inhibitor are secreted apically from Madin-Darby canine
      kidney (MDCK) cells, whereas two homologous family members, antithrombin and
      plasminogen activator inhibitor-1, are secreted in a nonpolarized fashion. cDNAs
      coding for chimeras composed of complementary portions of an apically targeted
      serpin and a nonsorted serpin were generated, expressed in MDCK cells, and the
      ratio between apical and basolateral secretion was analyzed. These experiments
      identified an amino-terminal sequence of corticosteroid binding globulin
      (residues 1-19) that is sufficient to direct a chimera with antithrombin mainly
      to the apical side. A deletion/mutagenesis analysis showed that no individual
      amino acid is absolutely required for the apical targeting ability of amino acids
      1-30 of corticosteroid binding globulin. The corresponding amino-terminal
      sequences of alpha1-antitrypsin and C1 inhibitor were also sufficient to confer
      apical sorting. Based on our results we suggest that the apical targeting ability
      is encoded in the conformation of the protein.

PMID- 11839736
TI  - Entry into cells and selective degradation of tRNAs by a cytotoxic member of the
      RNase A family.
AB  - Onconase (P-30 protein), an enzyme in the ribonuclease A superfamily, exerts
      cytostatic, cytotoxic, and antiviral activity when added to the medium of growing
      mammalian cells. We find that onconase enters living mammalian cells and
      selectively cleaves tRNA with no detectable degradation of rRNA. The RNA
      specificity of onconase in vitro using reticulocyte lysate and purified RNA
      substrates indicates that proteins associated with rRNA protect the rRNA from the
      onconase ribonucleolytic action contributing to the cellular tRNA selectivity of
      onconase. The onconase-mediated tRNA degradation in cells appears to be
      accompanied by increased levels of tRNA turnover and induction of tRNA synthesis
      perhaps in response to the selective toxin-induced loss of tRNA. Degradation
      products of tRNA(3)(Lys), which acts as a primer for HIV-1 replication, were
      clearly detected in cells infected with HIV-1 and treated with sublethal
      concentrations of onconase. However, a new synthesis of tRNA(3)(Lys) also seemed
      to occur in these cells resulting in plateauing of the steady-state levels of
      this tRNA. We conclude that the degradation of tRNAs may be a primary factor in
      the cytotoxic activity of onconase.

PMID- 11839737
TI  - A nucleotide switch in the Escherichia coli DnaA protein initiates chromosomal
      replication: evidnece from a mutant DnaA protein defective in regulatory ATP
      hydrolysis in vitro and in vivo.
AB  - The ATP-bound DnaA protein opens duplex DNA at the Escherichia coli origin of
      replication, leading to a series of initiation reactions in vitro. When loaded on
      DNA, the DNA polymerase III sliding clamp stimulates hydrolysis of DnaA-bound ATP
      in the presence of the IdaB/Hda protein, thereby yielding ADP-DnaA, which is
      inactive for initiation in vitro. This negative feedback regulation of DnaA
      activity is proposed to play a crucial role in the replication cycle. We here
      report that the mutant protein DnaA R334A is inert to hydrolysis of bound ATP,
      although its affinities for ATP and ADP remain unaffected. The ATP-bound DnaA
      R334A protein, but not the ADP form, initiates minichromosomal replication in
      vitro at a level similar to that seen for wild-type DnaA. When expressed at
      moderate levels in vivo, DnaA R334A is predominantly in the ATP-bound form,
      unlike the wild-type and DnaA E204Q proteins, which in vitro hydrolyze ATP in a
      sliding clamp- and IdaB/Hda-dependent manner. Furthermore, DnaA R334A, but not
      the wild-type or the DnaA E204Q proteins, promotes overinitiation of chromosomal
      replication. These in vivo data support a crucial role for bound nucleotides in
      regulating the activity of DnaA during replication. Based on a homology modeling
      analysis, we suggest that the Arg-334 residue closely interacts with bound
      nucleotides.

PMID- 11839738
TI  - Protein kinase C-delta (PKC-delta ) is activated by type I interferons and
      mediates phosphorylation of Stat1 on serine 727.
AB  - It is well established that engagement of the Type I interferon (IFN) receptor
      results in activation of JAKs (Janus kinases), which in turn regulate tyrosine
      phosphorylation of STAT proteins. Subsequently, the IFN-dependent tyrosine
      phosphorylated/activated STATs translocate to the nucleus to regulate gene
      transcription. In addition to tyrosine phosphorylation, phosphorylation of Stat1
      on serine 727 is essential for induction of its transcriptional activity, but the
      IFNalpha-dependent serine kinase that regulates such phosphorylation remains
      unknown. In the present study we provide evidence that PKC-delta, a member of the
      protein kinase C family of proteins, is activated during engagement of the Type I
      IFN receptor and associates with Stat1. Such an activation of PKC-delta appears
      to be critical for phosphorylation of Stat1 on serine 727, as inhibition of PKC
      delta activation diminishes the IFNalpha- or IFNbeta-dependent serine
      phosphorylation of Stat1. In addition, treatment of cells with the PKC-delta
      inhibitor rottlerin or the expression of a dominant-negative PKC-delta mutant
      results in inhibition of IFNalpha- and IFNbeta-dependent gene transcription via
      ISRE or GAS elements. Interestingly, PKC-delta inhibition also blocks activation
      of the p38 MAP kinase, the function of which is required for IFNalpha-dependent
      transcriptional regulation, suggesting a dual mechanism by which this kinase
      participates in the generation of IFNalpha responses. Altogether, these findings
      indicate that PKC-delta functions as a serine kinase for Stat1 and an upstream
      regulator of the p38 MAP kinase and plays an important role in the induction of
      Type I IFN-biological responses.

PMID- 11839739
TI  - Biochemical characterization of the human RAD51 protein. I. ATP hydrolysis.
AB  - The prototypical bacterial RecA protein promotes recombination/repair by
      catalyzing strand exchange between homologous DNAs. While the mechanism of strand
      exchange remains enigmatic, ATP-induced cooperativity between RecA protomers is
      critical for its function. A human RecA homolog, human RAD51 protein (hRAD51),
      facilitates eukaryotic recombination/repair, although its ability to hydrolyze
      ATP and/or promote strand exchange appears distinct from the bacterial RecA. We
      have quantitatively examined the hRAD51 ATPase. The catalytic efficiency
      (k(cat)/K(m)) of the hRAD51 ATPase was approximately 50-fold lower than the RecA
      ATPase. Altering the ratio of DNA/hRAD51 and including salts that stimulate DNA
      strand exchange (ammonium sulfate and spermidine) were found to affect the
      catalytic efficiency of hRAD51. The average site size of hRAD51 was determined to
      be approximately 3 nt (bp) for both single-stranded and double-stranded DNA.
      Importantly, hRAD51 lacks the magnitude of ATP-induced cooperativity that is a
      hallmark of RecA. Together, these results suggest that hRAD51 may be unable to
      coordinate ATP hydrolysis between neighboring protomers.

PMID- 11839740
TI  - Biochemical characterization of the human RAD51 protein. II. Adenosine nucleotide
      binding and competition.
AB  - RecA mediated homologous recombination requires cooperative ATP binding and
      hydrolysis to assume and maintain an active, extended DNA-protein (nucleoprotein)
      filament. Human RAD51 protein (hRAD51) lacks the magnitude of ATP-induced
      cooperativity and catalytic efficiency displayed by RecA. Here, we examined
      hRAD51 binding and ATPase inhibition pattern by ADP and ATP/adenosine 5'-O
      (thiotriphosphate) (ATPgammaS). hRAD51 fully saturates with ATP/ATPgammaS
      regardless of DNA cofactor (K(D) approximately 5 microm; 1 ATP/1 hRAD51). The
      binding of ADP to hRAD51 appeared bimodal. The first mode was identical to
      ATP/ATPgammaS binding (K(app1) approximately 3 microm; 1 ADP/1 hRAD51), while a
      second mode occurred at elevated ADP concentrations (K(app2) > or = 125 microm;
      >1 ADP/1 hRAD51). We could detect ADP --> ATP exchange in the high affinity ADP
      binding mode (K(app1)) but not the low affinity binding mode (K(app2)). At low
      ATP concentrations (<0.3 mm), ADP and ATPgammaS competitively inhibit the hRAD51
      ATPase (K(m)((app)) > K(m)). However, at high ATP (>0.3 mm), the hRAD51 ATPase
      was stimulated by concentrations of ATPgammaS that were 20-fold above the K(D).
      Ammonium sulfate plus spermidine decreased the affinity of hRAD51 for ADP
      substantially ( approximately 10-fold) and ATP modestly ( approximately 3-fold).
      Our results suggest that ATP binding is not rate-limiting but that the inability
      to sustain an active nucleoprotein filament probably restricts the hRAD51 ATPase.

PMID- 11839741
TI  - Biochemical characterization of the human RAD51 protein. III. Modulation of DNA
      binding by adenosine nucleotides.
AB  - Adenosine nucleotides affect the ability of RecA small middle dotsingle-stranded
      DNA (ssDNA) nucleoprotein filaments to cooperatively assume and maintain an
      extended structure that facilitates DNA pairing during recombination. Here we
      have determined that ADP and ATP/ATPgammaS affect the DNA binding and aggregation
      properties of the human RecA homolog human RAD51 protein (hRAD51). These studies
      have revealed significant differences between hRAD51 and RecA. In the presence of
      ATPgammaS, RecA forms a stable complex with ssDNA, while the hRAD51 ssDNA complex
      is destabilized. Conversely, in the presence of ADP and ATP, the RecA ssDNA
      complex is unstable, while the hRAD51 ssDNA complex is stabilized. We identified
      two hRAD51 small middle dotssDNA binding forms by gel shift analysis, which were
      distinct from a well defined RecA small middle dotssDNA binding form. The
      available evidence suggests that a low molecular weight hRAD51 small middle
      dotssDNA binding form (hRAD51 small middle dotssDNA(low)) correlates with active
      ADP and ATP processing. A high molecular weight hRAD51 small middle dotssDNA
      aggregate (hRAD51 small middle dotssDNA(high)) appears to correlate with a form
      that fails to process ADP and ATP. Our data are consistent with the notion that
      hRAD51 is unable to appropriately coordinate ssDNA binding with adenosine
      nucleotide processing. These observations suggest that other factors may assist
      hRAD51 in order to mirror RecA recombinational function.

PMID- 11839742
TI  - Identification of sterol-independent regulatory elements in the human ATP-binding
      cassette transporter A1 promoter: role of Sp1/3, E-box binding factors, and an
      oncostatin M-responsive element.
AB  - The ATP-binding cassette transporter A1 (ABCA1) shows a differentiation-, cAMP-,
      and sterol-dependent up-regulation in human monocytes. As part of an ongoing
      study, we investigated the proximal promoter regions that are highly conserved
      between the human and murine ABCA1 genes. Using reporter gene assays, we show
      here that a TATA box 24 bp upstream of the transcription initiation site is
      essential for promoter activity in RAW 264.7 and HepG2 cells, whereas further
      enhancement of transcriptional activity is mediated by the -175 bp promoter
      region. Gel shift assays revealed in vitro binding of Sp1 to a -91 GnC motif as
      well as binding of Sp1 and Sp3 to a -157 GnC promoter region. In co-transfection
      experiments using Drosophila S2 cells, we demonstrate that Sp3 competes with Sp1
      for binding to the -157 GnC motif and acts as a repressor. On the other hand,
      overexpression of Sp1 increased ABCA1 mRNA expression in HeLa cells and enhanced
      cellular cholesterol and phospholipid efflux in RAW 246.7 macrophages. We also
      show here that the conserved E-box at position -140 binds upstream stimulatory
      factors 1 and 2 and hepatic nuclear factor 1alpha and that mutagenesis of the E
      box enhanced constitutive ABCA1 expression in RAW 264.7 cells, implying a role
      for this element in silencing ABCA1 expression. Besides the functional importance
      for basal gene expression, we have identified that the core promoter region (-175
      to +224) is also responsible for the induction of ABCA1 by the cytokine
      oncostatin M, resulting in a rapid increase in ABCA1 mRNA levels in HepG2 cells.
      Interestingly, this oncostatin M-induced expression is not dependent on the
      currently known sequence motifs in the ABCA1 promoter. In conclusion, a
      functional complex of cis-elements within the proximal human ABCA1 promoter
      associated with the transcription factors Sp1/3, upstream stimulatory factors 1
      and 2, and hepatic nuclear factor 1alpha has been characterized, which allows a
      subtle tissue-specific regulation of ABCA1 gene expression.

PMID- 11839743
TI  - IKK-i and TBK-1 are enzymatically distinct from the homologous enzyme IKK-2:
      comparative analysis of recombinant human IKK-i, TBK-1, and IKK-2.
AB  - NF-kappaB is sequestered in the cytoplasm by the inhibitory IkappaB proteins.
      Stimulation of cells by agonists leads to the rapid phosphorylation of IkappaBs
      leading to their degradation that results in NF-kappaB activation. IKK-1 and IKK
      2 are two direct IkappaB kinases. Two recently identified novel IKKs are IKK-i
      and TBK-1. We have cloned, expressed, and purified to homogeneity recombinant
      human (rh)IKK-i and rhTBK-1 and compared their enzymatic properties with those of
      rhIKK-2. We show that rhIKK-i and rhTBK-1 are enzymatically similar to each
      other. We demonstrate by phosphopeptide mapping and site-specific mutagenesis
      that rhIKK-i and rhTBK-1 are phosphorylated on serine 172 in the mitogen
      activated protein kinase kinase activation loop and that this phosphorylation is
      necessary for kinase activity. Also, rhIKK-i and rhTBK-1 have differential
      peptide substrate specificities compared with rhIKK-2, the mitogen-activated
      protein kinase kinase activation loop of IKK-2 being a more favorable substrate
      than the IkappaBalpha peptide. Finally, using analogs of ATP, we demonstrate
      unique differences in the ATP-binding sites of rhIKK-i, rhTBK-1, and rhIKK-2.
      Thus, although these IKKs are structurally similar, their enzymatic properties
      may provide insights into their unique functions.

PMID- 11839744
TI  - MobA, the DNA strand transferase of plasmid R1162: the minimal domain required
      for DNA processing at the origin of transfer.
AB  - MobA is a DNA strand transferase encoded by the plasmid R1162 and required for
      plasmid DNA processing during conjugal transfer. The smallest active fragment was
      identified using phage display and partial enzymatic digestion of the purified
      protein. This fragment, consisting of approximately the first 184 amino acids, is
      able to bind and cleave its normal DNA substrate, the origin of transfer (oriT).
      Smaller fragments having one of these activities were not obtained. An active
      intermediate consisting of MobA linked to DNA was isolated and used to show that
      a single molecule of MobA is sufficient to carry out all of the DNA processing
      steps during transfer. These results, along with those obtained earlier, point to
      a single large, active site in MobA that makes several different contacts along
      the oriT DNA strand.

PMID- 11839745
TI  - The crystal structure of rat liver AKR7A1. A dimeric member of the aldo-keto
      reductase superfamily.
AB  - The structure of the rat liver aflatoxin dialdehyde reductase (AKR7A1) has been
      solved to 1.38-A resolution. Although it shares a similar alpha/beta-barrel
      structure with other members of the aldo-keto reductase superfamily, AKR7A1 is
      the first dimeric member to be crystallized. The crystal structure also reveals
      details of the ternary complex as one subunit of the dimer contains NADP(+) and
      the inhibitor citrate. Although the underlying catalytic mechanism appears
      similar to other aldo-keto reductases, the substrate-binding pocket contains
      several charged amino acids (Arg-231 and Arg-327) that distinguish it from
      previously characterized aldo-keto reductases with respect to size and charge.
      These differences account for the substrate specificity for 4-carbon acid
      aldehydes such as succinic semialdehyde and 2-carboxybenzaldehyde as well as for
      the idiosyncratic substrate aflatoxin B(1) dialdehyde of this subfamily of
      enzymes. Structural differences between the AKR7A1 ternary complex and apoenzyme
      reveal a significant hinged movement of the enzyme involving not only the loops
      of the structure but also parts of the alpha/beta-barrel most intimately involved
      in cofactor binding.

PMID- 11839746
TI  - Substrate binding of gelatinase B induces its enzymatic activity in the presence
      of intact propeptide.
AB  - Expression of gelatinase B (matrix metalloprotease 9) in human placenta is
      developmentally regulated, presumably to fulfill a proteolytic function. Here we
      demonstrate that gelatinolytic activity in situ, in tissue sections of term
      placenta, is co-localized with gelatinase B. Judging by molecular mass, however,
      all the enzyme extracted from this tissue was found in a proform. To address this
      apparent incongruity, we examined the activity of gelatinase B bound to either
      gelatin- or type IV collagen-coated surfaces. Surprisingly, we found that upon
      binding, the purified proenzyme acquired activity against both the fluorogenic
      peptide (7-methoxycoumarin-4-yl)-acetic acid (MCA)-Pro-Leu-Gly-Leu-3-(2,4
      dinitrophenyl)-l-2,3-diaminopropionyl-Ala-Arg-NH(2) and gelatin substrates,
      whereas its propeptide remained intact. These results suggest that although
      activation of all known matrix metalloproteases in vitro is accomplished by
      proteolytic processing of the propeptide, other mechanisms, such as binding to a
      ligand or to a substrate, may lead to a disengagement of the propeptide from the
      active center of the enzyme, causing its activation.

PMID- 11839747
TI  - Solution structure and dynamics of the lipoic acid-bearing domain of human
      mitochondrial branched-chain alpha-keto acid dehydrogenase complex.
AB  - The lipoyl-bearing domain (LBD) of the transacylase (E2) subunit of the branched
      chain alpha-keto acid dehydrogenase complex plays a central role in substrate
      channeling in this mitochondrial multienzyme complex. We have employed
      multidimensional heteronuclear NMR techniques to determine the structure and
      dynamics of the LBD of the human branched-chain alpha-keto acid dehydrogenase
      complex (hbLBD). Similar to LBD from other members of the alpha-keto acid
      dehydrogenase family, the solution structure of hbLBD is a flattened beta-barrel
      formed by two four-stranded antiparallel beta-sheets. The lipoyl Lys(44) residue
      resides at the tip of a beta-hairpin comprising a sharp type I beta-turn and the
      two connecting beta-strands 4 and 5. A prominent V-shaped groove formed by a
      surface loop, L1, connecting beta 1- and beta 2-strands and the lipoyl lysine
      beta-hairpin constitutes the functional pocket. We further applied reduced
      spectral density functions formalism to extract dynamic information of hbLBD from
      (15)N-T(1), (15)N-T(2), and ((1)H-(15)N) nuclear Overhauser effect data obtained
      at 600 MHz. The results showed that residues surrounding the lipoyl lysine region
      comprising the L1 loop and the Lys(44) beta-turn are highly flexible, whereas
      beta-sheet S1 appears to display a slow conformational exchange process.

PMID- 11839748
TI  - Activation of clg, a novel dbl family guanine nucleotide exchange factor gene, by
      proviral insertion at evi24, a common integration site in B cell and myeloid
      leukemias.
AB  - Retroviruses induce leukemia in inbred strains of mice by activating cellular
      proto-oncogenes and/or inactivating tumor suppressors. The proviral integration
      sites in these leukemias provide powerful genetic tags for disease gene
      identification. Here we show that Evi24, a common site of retroviral integration
      in AKXD B cell and BXH-2 myeloid leukemias, contains a novel Dbl family guanine
      nucleotide exchange factor gene. We have designated this gene Clg (common-site
      lymphoma/leukemia guanine nucleotide exchange factor). Proviral integrations on
      chromosome 7 at Evi24 are located 7.6-10.3 kb upstream of Clg and increased Clg
      expression 2-5-fold compared with leukemias lacking proviral integrations at
      Evi24. Clg contains Dbl/pleckstrin homology domains with substantial sequence
      homology to many Rho family activators, including the transforming Dbl and
      Dbs/Ost oncogenes. Nucleotide exchange assays indicated that Clg specifically
      activated nucleotide exchange on Cdc42, but not RhoA or Rac1, in vitro. NIH 3T3
      transfection studies showed that overexpression of full-length and carboxyl
      terminally truncated forms of Clg morphologically transformed NIH 3T3 cells. This
      study and studies showing that the human homolog of EVI24 is located in a region
      of 19q13 frequently amplified in B cell lymphomas and pancreatic and breast
      cancers implicate Clg and Cdc42 activation in mouse and human cancers.

PMID- 11839749
TI  - The Rho exchange factor Net1 is regulated by nuclear sequestration.
AB  - Net1 is a guanine nucleotide exchange factor specific for the small GTPase Rho.
      Oncogenic activation of Net1 occurs by truncation of the N-terminal part of the
      protein, which functions as a negative regulatory domain. Here, we have
      investigated the mechanism of Net1 regulation via its N terminus. We find that
      Net1 localizes to the nucleus, whereas oncogenic Net1 is found in the cytoplasm.
      Nuclear import of Net1 is mediated by two nuclear localization signals present in
      the N terminus of the protein, and forced cytoplasmic localization of Net1 is
      sufficient to activate Rho. In addition, the pleckstrin homology (PH) domain of
      Net1 acts as a nuclear export signal. Because an amino acid substitution in the
      PH domain that inhibits guanine nucleotide exchange factor activity does not
      inhibit nuclear export, we conclude that this PH domain has at least two
      functions. Together, our results suggest that Net1 can shuttle in and out of the
      nucleus, and that activation of Rho by Net1 is controlled by changes in its
      subcellular localization.

PMID- 11839750
TI  - Caspase-mediated parkin cleavage in apoptotic cell death.
AB  - The parkin protein is important for the survival of the neurons that degenerate
      in Parkinson's disease as demonstrated by disease-causing lesions in the parkin
      gene. The Chinese hamster ovary and the SH-SY5Y cell line stably expressing
      recombinant human parkin combined with epitope-specific parkin antibodies were
      used to investigate the proteolytic processing of human parkin during apoptosis
      by immunoblotting. Parkin is cleaved during apoptosis induced by okadaic acid,
      staurosporine, and camptothecin, thereby generating a 38-kDa C-terminal fragment
      and a 12-kDa N-terminal fragment. The cleavage was not significantly affected by
      the disease-causing mutations K161N, G328E, T415N, and G430D and the polymorphism
      R366W. Parkin and its 38-kDa proteolytic fragment is preferentially associated
      with vesicles, thereby indicating that cleavage is a membrane-associated event.
      The proteolysis is sensitive to inhibitors of caspases. The cleavage site was
      mapped by site-directed mutagenesis of potential aspartic residues and revealed
      that mutation of Asp-126 alone abrogated the parkin cleavage. The tetrapeptide
      aldehyde LHTD-CHO, representing the amino acid sequence N-terminal to the
      putative cleavage site was an efficient inhibitor of parkin cleavage. This
      suggests that parkin function is compromised in neuropathological states
      associated with an increased caspase activation, thereby further adding to the
      cellular stress.

PMID- 11839751
TI  - Evidence that arachidonate 15-lipoxygenase 2 is a negative cell cycle regulator
      in normal prostate epithelial cells.
AB  - 15-Lipoxygenase 2 (15-LOX2) is a recently cloned human lipoxygenase that shows
      tissue-restricted expression in prostate, lung, skin, and cornea. The protein
      level and enzymatic activity of 15-LOX2 have been shown to be down-regulated in
      prostate cancers compared with normal and benign prostate tissues. The biological
      function of 15-LOX2 and the role of loss of 15-LOX2 expression in prostate
      tumorigenesis, however, remain unknown. We report the cloning and functional
      characterization of 15-LOX2 and its three splice variants (termed 15-LOX2sv-a, 15
      LOX2sv-b, and 15-LOX2sv-c) from primary prostate epithelial cells. Western
      blotting with multiple primary prostate cell strains and prostate cancer cell
      lines reveals that the expression of 15-LOX2 is lost in all prostate cancer cell
      lines, accompanied by decreased enzymatic activity revealed by liquid
      chromatography/tandem mass spectrometry analyses. Further experiments show that
      the loss of 15-LOX2 expression results from transcriptional repression caused by
      mechanism(s) other than promoter hypermethylation or histone deacetylation.
      Subsequent functional studies indicate the following: 1) the 15-LOX2 product,
      15(S)-hydroxyeicosatetraenoic acid, inhibits prostate cancer cell cycle
      progression; 2) 15-LOX2 expression in primary prostate epithelial cells is
      inversely correlated with cell cycle; and 3) restoration of 15-LOX2 expression in
      prostate cancer cells partially inhibits cell cycle progression. Taken together,
      these results suggest that 15-LOX2 could be a suppressor of prostate cancer
      development, which functions by restricting cell cycle progression.

PMID- 11839752
TI  - alpha 2-Macroglobulin exposure reduces calcium responses to N-methyl-D-aspartate
      via low density lipoprotein receptor-related protein in cultured hippocampal
      neurons.
AB  - There is increasing evidence that the low-density lipoprotein receptor-related
      protein (LRP) can function as a signaling link in the central nervous system. To
      investigate the pathophysiological role of LRP in the central nervous system, we
      examined the effects of activated alpha(2)-macroglobulin (alpha2M*), a ligand of
      LRP, on intracellular calcium signaling in cultured rat hippocampal neurons.
      Neuronal effects of alpha2M* (50 nm) were assessed by a comparison of calcium
      signals produced in control and alpha2M*-pretreated neurons by N-methyl-D
      aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid.
      alpha2M* pretreatment significantly decreased the calcium signals to NMDA,
      whereas little change was observed for the signals to alpha-amino-3-hydroxy-5
      methyl-4-isoxazole propionic acid. Native alpha2M, which is not a ligand for LRP,
      did not affect signals to NMDA. The receptor-associated protein prevented
      alpha2M*-induced decrease of calcium responses to NMDA, suggesting that alpha2M*
      exerted its effects through an LRP-mediated pathway. Experiments changing calcium
      sources demonstrated that alpha2M* pretreatment altered calcium responses to NMDA
      by primarily changing extracellular calcium influx and subsequently affecting
      calcium release from intracellular calcium stores. Immunoblot analysis
      demonstrated that alpha2M* caused a reduction in the levels of the NMDA receptor
      subunit, NMDAR1. These results suggest that alpha2M* can alter the neuronal
      response to excitatory neurotransmitters and that alpha2M* pretreatment
      selectively reduced the calcium responses to NMDA by down-regulating the NMDA
      receptor.

PMID- 11839753
TI  - Cholesterol-modulating agents selectively inhibit calcium influx induced by
      chemoattractants in human neutrophils.
AB  - The effects of cholesterol-perturbing agents on the mobilization of calcium
      induced upon the stimulation of human neutrophils by chemotactic factors were
      tested. Methyl-beta-cyclodextrin and filipin did not alter the initial peak of
      calcium mobilization but shortened the duration of the calcium spike that
      followed the addition of fMet-Leu-Phe. These agents also inhibited the influx of
      Mn(2+) induced by fMet-Leu-Phe or thapsigargin. Methyl-beta-cyclodextrin and
      filipin completely abrogated the mobilization of calcium induced by 10(-10) m
      platelet-activating factor, which at this concentration depends to a major extent
      on an influx of calcium as well as the influx of calcium induced by 10(-7) m
      platelet-activating factor. On the other hand, methyl-beta-cyclodextrin and
      filipin enhanced the mobilization of calcium induced by ligation of FcgammaRIIA,
      an agonist that did not induce a detectable influx of calcium. Finally, methyl
      beta-cyclodextrin and filipin enhanced the stimulation of the profile of tyrosine
      phosphorylation, the activity of phospholipase D (PLD), and the production of
      superoxide anions induced by fMet-Leu-Phe. These results suggest that the calcium
      channels utilized by chemotactic factors in human neutrophils are either located
      in cholesterol-rich regions of the plasma membrane, or that the mechanisms that
      lead to their opening depend on the integrity of these microdomains.

PMID- 11839754
TI  - Nitric oxide (NO) induces nitration of protein kinase Cepsilon (PKCepsilon ),
      facilitating PKCepsilon translocation via enhanced PKCepsilon -RACK2
      interactions: a novel mechanism of no-triggered activation of PKCepsilon.
AB  - Activation of protein kinase C (PKC) epsilon by nitric oxide (NO) has been
      implicated in the development of cardioprotection. However, the cellular
      mechanisms underlying the activation of PKCepsilon by NO remain largely unknown.
      Nitration of protein tyrosine residues has been shown to alter functions of a
      variety of proteins, and NO-derived peroxynitrite is known as a strong nitrating
      agent. In this investigation, we demonstrate that NO donors promote translocation
      and activation of PKCepsilon in an NO- and peroxynitrite-dependent fashion. NO
      induces peroxynitrite-mediated tyrosine nitration of PKCepsilon in rabbit
      cardiomyocytes in vitro, and nitrotyrosine residues were also detected on
      PKCepsilon in vivo in the rabbit myocardium preconditioned with NO donors.
      Furthermore, coimmunoprecipitation of PKCepsilon and its receptor for activated C
      kinase, RACK2, illustrated a peroxynitrite-dependent increase in PKCepsilon-RACK2
      interactions in NO donor-treated cardiomyocytes. Moreover, using an enzyme-linked
      immunosorbent assay-based protein-protein interaction assay, PKCepsilon proteins
      treated with the peroxynitrite donor SIN-1 exhibited enhanced binding to RACK2 in
      an acellular environment. Our data demonstrate that post-translational
      modification of PKCepsilon by NO donors, namely nitration of PKCepsilon,
      facilitates its interaction with RACK2 and promotes translocation and activation
      of PKCepsilon. These findings offer a plausible novel mechanism by which NO
      activates the PKC signaling pathway.

PMID- 11839755
TI  - Galectin-3 translocates to the perinuclear membranes and inhibits cytochrome c
      release from the mitochondria. A role for synexin in galectin-3 translocation.
AB  - Galectin-3 is a multifunctional oncogenic protein found in the nucleus and
      cytoplasm and also the extracellular milieu. Although recent studies demonstrated
      an anti-apoptotic activity of galectin-3, neither the functional site nor the
      mechanism of how galectin-3 regulates apoptosis is known. In this study, we
      examined the subcellular localization of galectin-3 during apoptosis and
      investigated its anti-apoptotic actions. We report that galectin-3 translocates
      to the perinuclear membrane following a variety of apoptotic stimuli. Confocal
      microscopy and biochemical analysis revealed that galectin-3 is enriched in the
      mitochondria and prevents mitochondrial damage and cytochrome c release. Using a
      yeast two-hybrid system, we screened for galectin-3-interacting proteins that
      regulate galectin-3 localization and anti-apoptotic activity. Synexin, a Ca(2+)-
      and phospholipid-binding protein, was one of the proteins identified. We
      confirmed direct interaction between galectin-3 and synexin by glutathione S
      transferase pull-down assay in vitro. We showed that galectin-3 failed to
      translocate to the perinuclear membranes when expression of synexin was down
      regulated using an oligodeoxyribonucleotide complementary to the synexin mRNA,
      suggesting a role for synexin in galectin-3 trafficking. Furthermore, synexin
      down-regulation abolished anti-apoptotic activity of galectin-3. Taken together,
      these results suggest that synexin mediates galectin-3 translocation to the
      perinuclear mitochondrial membranes, where it regulates mitochondrial integrity
      critical for apoptosis regulation.

PMID- 11839756
TI  - Isolation and characterization of a novel eosinophil-specific galectin released
      into the lungs in response to allergen challenge.
AB  - A novel galectin cDNA (galectin-14) was cloned from ovine eosinophil-rich
      leukocytes by low stringency reverse transcriptase-PCR and cDNA library
      screening. Data base searches indicate that this gene encodes a novel prototype
      galectin that contains one putative carbohydrate recognition domain and exhibits
      most identity to galectin-9/ecalectin, a potent eosinophil chemoattractant. The
      sugar binding properties of the recombinant molecule were confirmed by a
      hemagglutination assay and lactose inhibition. The mRNA and protein of galectin
      14 are expressed at high levels in eosinophil-rich cell populations. Flow
      cytometry and cytospot staining demonstrate that the protein localizes to the
      cytoplasmic, but not the granular, compartment of eosinophils. In contrast,
      galectin-14 mRNA and protein were not detected in neutrophils, macrophages, or
      lymphocytes. Western blot analysis of bronchoalveolar lavage fluid indicates that
      galectin-14 is released from eosinophils into the lumen of the lungs after
      challenge with house dust mite allergen. The restricted expression of this novel
      galectin to eosinophils and its release into the lumen of the lung in a sheep
      asthma model indicates that it may play an important role in eosinophil function
      and allergic inflammation.

PMID- 11839757
TI  - Two initiator-like elements are required for the combined activation of the human
      apolipoprotein C-III promoter by upstream stimulatory factor and hepatic nuclear
      factor-4.
AB  - Human apoC-III (-890/+24) promoter activity is strongly activated by hepatic
      nuclear factor (HNF)-4 through its binding to the proximal (-87/-72) element B.
      This site overlaps the binding site for an activity that we identified as the
      ubiquitously expressed upstream stimulatory factor (USF) (Ribeiro, A., Pastier,
      D., Kardassis, D., Chambaz, J., and Cardot, P. (1999) J. Biol. Chem. 274, 1216
      1225). In the present study, we characterized the relationship between USF and
      HNF-4 in the activation of human apoC-III transcription. Although USF and HNF-4
      binding to element B is mutually exclusive, co-transfection experiments in HepG2
      cells surprisingly showed a combined effect of USF and HNF-4 in the
      transactivation of the (-890/+24) apoC-III promoter. This effect only requires
      the proximal region (-99/+24) of the apoC-III promoter and depends neither on USF
      binding to its cognate site in element B nor on a USF-dependent facilitation of
      HNF-4 binding to its site. By contrast, we found by electrophoretic mobility
      shift assay and footprinting analysis two USF low affinity binding sites, located
      within the proximal promoter at positions -58/-31 (element II) and -19/-4
      (element I), which are homologous to initiator-like element sequence. Co
      transfection experiments in HepG2 cells show that a mutation in element II
      reduces 2-fold the USF transactivation effect on the proximal promoter of apoC
      III and that a mutation in element I inhibits the combined effect of USF and HNF
      4. In conclusion, these initiator-like elements are directly involved in the
      transactivation of the apoC-III promoter by USF and are necessary to the combined
      effect between USF and HNF-4 for the apoC-III transcription.

PMID- 11839758
TI  - Adenylyl cyclase Rv1264 from Mycobacterium tuberculosis has an autoinhibitory N
      terminal domain.
AB  - Mycobacterium tuberculosis contains 15 class III adenylyl cyclase genes. The gene
      Rv1264 is predicted to be composed of two distinct protein modules. The C
      terminus seems to code for a catalytic domain belonging to a subfamily of
      adenylyl cyclase isozymes mostly found in Gram-positive bacteria. The expressed
      protein was shown to function as a homodimeric adenylyl cyclase (1 micromol of
      cAMP x mg(-1) x min(-1)). In analogy to the structure of the mammalian adenylyl
      cyclase catalyst, six amino acids were targeted by point mutations and found to
      be essential for catalysis. The N-terminal region represents a novel protein
      domain, the occurrence of which is restricted to several adenylyl cyclases
      present in Gram-positive bacteria. The purified full-length enzyme was 300-fold
      less active than the catalytic domain alone. Thus, the N-terminal domain appeared
      to be autoinhibitory. The N-terminal domain contains three prominent polar amino
      acid residues (Asp(107), Arg(132), and Arg(191)) that are invariant in all seven
      sequences of this domain currently available. Mutation of Asp(107) to Ala relaxed
      the inhibition and resulted in a 6-fold increase in activity of the Rv1264
      holoenzyme, thus supporting the role of this domain as a potential novel
      regulator of adenylyl cyclase activity.

PMID- 11839759
TI  - Disabling a C-terminal autoinhibitory control element in endothelial nitric-oxide
      synthase by phosphorylation provides a molecular explanation for activation of
      vascular NO synthesis by diverse physiological stimuli.
AB  - Calmodulin-dependent activation of endothelial nitric-oxide synthase is generally
      considered to follow a transient increase in intracellular calcium levels.
      However, a number of physiological stimuli (e.g. endothelial shear-stress,
      insulin) are known to activate endothelial nitric oxide (eNOS) via a non
      classical, "calcium-independent" pathway. Recent findings demonstrate that such
      stimuli elicit the phosphorylation of a C-terminal residue in eNOS (Ser(1179) in
      the bovine isoform), rendering eNOS active at resting levels of intracellular
      calcium. However, the mechanistic basis for this mode of eNOS activation remains
      unknown. Protein modeling led us to consider that the C terminus of eNOS may
      fulfill an autoinhibitory function that can be disrupted by phosphorylation of
      serine 1179. To test this possibility we contrasted the phenotype of wild type
      bovine eNOS with that of a mutant lacking C-terminal residues 1179-1205 (CDelta27
      eNOS). Despite no observed difference in calmodulin affinity, CDelta27 eNOS
      exhibited a 5-fold reduction in EC(50) for calcium and a 2-4-fold increase in
      maximal catalytic activities. In these phenotypic properties, CDelta27 accurately
      mimics phospho-Ser(1179) wild type eNOS. We conclude that the C terminus imposes
      a significant barrier to the activation of eNOS by calmodulin binding and that
      this barrier can be functionally disabled by Ser(1179) phosphorylation-elicited
      enzyme activation.

PMID- 11839760
TI  - Effects of a guanine-derived formamidopyrimidine lesion on DNA replication:
      translesion DNA synthesis, nucleotide insertion, and extension kinetics.
AB  - 2,6-Diamino-4-hydroxy-5-formamidopyrimidine derived from guanine (FapyG) is a
      major DNA lesion formed by reactive oxygen species. In this study, a defined
      oligonucleotide template containing a 5-N-methylated analog of FapyG (mFapyG) was
      prepared, and its effect on DNA replication was quantitatively assessed in vitro.
      The results were further compared with those obtained for 7,8-dihydro-8
      oxoguanine and an apurinic/apyrimidinic site embedded in the same sequence
      context. mFapyG constituted a fairly strong but not absolute block to DNA
      synthesis catalyzed by Escherichia coli DNA polymerase I Klenow fragment with and
      without an associated 3'-5' exonuclease activity, thereby permitting translesion
      synthesis with a limited efficiency. The efficiency of translesion synthesis was
      G > 7,8-dihydro-8-oxoguanine > mFapyG > apurinic/apyrimidinic site. Analysis of
      the nucleotide insertion (f(ins) = V(max)/K(m) for insertion) and extension
      (f(ext) = V(max)/K(m) for extension) efficiencies for mFapyG revealed that the
      extension step constituted a major kinetic barrier to DNA synthesis. When mFapyG
      was bypassed, dCMP, a cognate nucleotide, was preferentially inserted opposite
      the lesion (dCMP (relative f(ins) = 1) dTMP (2.4 x 10(-4)) approximately dAMP
      (8.1 x 10(-5)) > dGMP (4.5 x 10(-7))), and the primer terminus containing a
      mFapyG:C pair was most efficiently extended (mFapyG:C (relative f(ext) = 1) >
      mFapyG:T (4.6 x 10(-3)) mFapyG:A and mFapyG:G (extension not observed)). Thus,
      mFapyG is a potentially lethal but not premutagenic lesion.

PMID- 11839761
TI  - The activity of the extracellular signal-regulated kinase 2 is regulated by
      differential phosphorylation in the activation loop.
AB  - The mitogen-activated protein kinases (MAP kinases) play a central role in
      signaling pathways initiated by extracellular stimuli such as growth factors,
      cytokines, and various forms of environmental stress. Full activation of the MAP
      kinases requires dual phosphorylation of the Thr and Tyr residues in the TXY
      motif of the activation loop by MAP kinase kinases. Interestingly, down
      regulation of MAP kinase activity can be initiated by multiple Ser/Thr
      phosphatases, Tyr-specific phosphatases, and dual-specificity phosphatases. This
      would inevitable lead to the formation of monophosphorylated MAP kinases.
      However, in much of the literature investigating MAP kinase signaling, there has
      been the implicit assumption that the monophosphorylated forms are inactive.
      Thus, the significance for the need of multiple phosphatases in regulating MAP
      kinase activity is not clear, and the biological functions of these
      monophosphorylated MAP kinases are currently unknown. We have prepared
      extracellular signal-regulated protein kinase 2 (ERK2) in all phosphorylated
      forms and kinetically characterized them using two proteins (the myelin basic
      protein and Elk-1) and ATP as substrates. Our results revealed that a single
      phosphorylation in the activation loop of ERK2 produces an intermediate activity
      state. Thus, the catalytic efficiencies of the monophosphorylated ERK2/pY and
      ERK2/pT (ERK2 phosphorylated on Tyr-185 and Thr-183, respectively) are
      approximately 2-3 orders of magnitude higher than that of the unphosphorylated
      ERK2 and are only 1-2 orders of magnitude lower than that of the fully active
      bisphosphorylated ERK2/pTpY. This raises the possibility that the
      monophosphorylated ERK2s may have distinct biological roles in vivo. Different
      phosphorylation states in the activation loop could be linked to graded effects
      on a single ERK2 function. Alternatively, they could be linked to distinct ERK2
      functions. Although less active than the bisphosphorylated species, the
      monophosphorylated ERK2s may differentially phosphorylate pathway components.

PMID- 11839762
TI  - Synthesis and biological evaluation in vitro of a selective, high potency peptide
      agonist of human melanin-concentrating hormone action at human melanin
      concentrating hormone receptor 1.
AB  - Human melanin-concentrating hormone (hMCH) is a nonselective natural ligand for
      the human melanin-concentrating hormone receptors: hMCH-1R and hMCH-2R.
      Similarly, the smaller peptide encompassing the disulfide ring and Arg(6) of
      hMCH, Ac-Arg(6)-cyclo(S-S)(Cys(7)-Met(8)-Leu(9)-Gly(10)-Arg(11)-Val(12)-Tyr(13)
      Arg(14)-Pro(15)-Cys(16))-NH(2), Ac-hMCH(6-16)-NH(2), binds to and activates
      equally well both human MCH receptors present in the brain. To separate the
      physiological functions of hMCH-1R from those of hMCH-2R, new potent and hMCH-1R
      selective agonists are necessary. In the present study, analogs of Ac-hMCH(6-16)
      NH(2) were prepared and tested in binding and functional assays on cells
      expressing the MCH receptors. In these peptides, Arg in position 6 was replaced
      with various d-amino acids and/or Gly in position 10 was substituted with various
      L-amino acids. Several of the new compounds turned out to be potent agonists at
      hMCH-1R with improved selectivity over hMCH-2R. For example, peptide 26 with d
      Arg in place of L-Arg in position 6 and Asn in place of Gly in position 10, Ac
      dArg(6)-cyclo(S-S)(Cys(7)-Met(8)-Leu(9)-Asn(10)-Arg(11)-Val(12)-Tyr(13)-Arg(14)
      Pro(15)-Cys(16))-NH(2), was a potent hMCH-1R agonist (IC(50) = 0.5 nm, EC(50) =
      47 nm) with more than 200-fold selectivity with respect to hMCH-2R. Apparently,
      these structural changes in positions 6 and 10 results in peptide conformations
      that allow for efficient interactions with hMCH-1R but are unfavorable for
      molecular recognition at hMCH-2R.

PMID- 11839764
TI  - The EIIIA segment of fibronectin is a ligand for integrins alpha 9beta 1 and
      alpha 4beta 1 providing a novel mechanism for regulating cell adhesion by
      alternative splicing.
AB  - Alternative splicing of the fibronectin gene transcript gives rise to forms that
      include the EIIIA (or ED-A) segment. EIIIA-containing fibronectins are
      prominently expressed during embryogenesis and wound healing and appear to
      mediate changes in cell adhesion and gene expression. Nonetheless, integrins that
      bind the EIIIA segment have not been identified. We previously mapped the epitope
      for two function-blocking monoclonal antibodies to the C-C' loop region of the
      EIIIA segment (Liao, Y.-F., Wieder, K. G., Classen, J. M., and Van De Water, L.
      (1999) J. Biol. Chem. 274, 17876-17884). The sequence of this epitope
      ((39)PEDGIHELFP(48)) resembles the sequence within tenascin-C to which the
      integrin alpha(9)beta(1) binds. We now report that either integrin
      alpha(9)beta(1) or alpha(4)beta(1) can mediate cell adhesion to the EIIIA
      segment. Moreover, this interaction is blocked both by epitope-mapped EIIIA
      antibodies as well as by the respective anti-integrins. Deletion mutants of the
      EIIIA segment that include the C-C' loop and flanking sequence bind cells
      expressing either alpha(9)beta(1) or alpha(4)beta(1). Adhesion of alpha(4)beta(1)
      containing MOLT-3 cells to the EIIIA segment stimulates phosphorylation of p44/42
      MAP kinase. Our observation that two integrins bind the EIIIA segment establishes
      a novel mechanism by which cell adhesion to fibronectin is regulated by
      alternative splicing.

PMID- 11839763
TI  - Hypobetalipoproteinemic mice with a targeted apolipoprotein (Apo) B-27.6
      specifying mutation: in vivo evidence for an important role of amino acids 1254
      1744 of ApoB in lipid transport and metabolism of the apoB-containing
      lipoprotein.
AB  - Carboxyl-terminal deletion of apoB-100 may impair its triglyceride (TG)
      transporting capability and alter its catabolism. Here, we compare our newly
      generated apoB gene (Apob)-targeted apoB-27.6-bearing mice to our previously
      reported apoB-38.9 mice to understand further the relationship between the size
      of a truncated apoB variant and its function/metabolism in vivo. The apoB-27.6
      specifying mutation produces a premature stop codon six amino acids (aa)
      downstream of the last codon of mouse Apob exon 24 (corresponding to aa 1254 of
      human apoB-100). ApoB-27.6 transcripts were 3- and 5-fold more abundant than apoB
      wild type and apoB-38.9 transcripts in the liver. Likewise, hepatic secretion
      rates of apoB-27.6 were 7-fold higher than those of apoB-48 and apoB-38.9. In
      contrast, apoB-27.6 heterozygotes (Apob(27.6/+)) had lower hepatic TG secretion
      rates and higher liver TG contents than both apoB-38.9 heterozygotes
      (Apob(38.9/+)) and apoB wild type mice (Apob(+/+)). ApoB-27.6 was secreted by
      Apob(27.6/+) hepatocytes as dense high density lipoprotein particles. Moreover,
      despite its high secretion rates, apoB-27.6 was barely detectable in plasma.
      Disruption of apoE gene in Apob(38.9/+) and Apob(27.6/+) dramatically increased
      plasma levels of apoB-38.9 as well as apoB-48 but caused no change in plasma apoB
      27.6 concentrations. Finally, the birth rate of apoB-27.6 homozygotes
      (Apob(27.6/27.6)) from intercrosses of Apob(27.6/+) was 7-fold lower than that of
      Apob(38.9/38.9) from Apob(38.9/+) intercrosses (1.8% versus 12%). Crossbreeding
      of Apob(27.6/27.6) and Apob(38.9/38.9) produced viable Apob(27.6/38.9) offspring,
      but Apob(27.6/27.6) intercrosses produced no offspring. Together, these results
      demonstrate in vivo that the apoB-27.6-apoB-38.9 peptide segment (aa 1254-1744)
      plays a critical role, not only in supporting hepatic TG-secretion and in
      modulating catabolism of apoB-containing lipoproteins, but also in normal mouse
      embryonic development.

PMID- 11839765
TI  - Inhibition of protein geranylgeranylation and RhoA/RhoA kinase pathway induces
      apoptosis in human endothelial cells.
AB  - Geranylgeranylation of RhoA small G-protein is essential for its localization to
      cell membranes and for its biological functions. Many RhoA effects are mediated
      by its downstream effector RhoA kinase. The role of protein geranylgeranylation
      and the RhoA pathway in the regulation of endothelial cell survival has not been
      elucidated. The hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitor lovastatin
      depletes cellular pools of geranylgeranyl pyrophosphate and farnesol
      pyrophosphate and thereby inhibits both geranylgeranylation and farnesylation.
      Human umbilical vein endothelial cells (HUVECs) were exposed to lovastatin (3
      microm-30 microm) for 48 h, and cell death was quantitatively determined by
      cytoplasmic histone-associated DNA fragments as well as caspase-3 activity. The
      assays showed that lovastatin caused a dose-dependent endothelial cell death. The
      addition of geranylgeraniol, which restores geranylgeranylation, rescued HUVEC
      from apoptosis. The geranylgeranyltransferase inhibitor GGTI-298, but not the
      farnesyltransferase inhibitor FTI-277, induced apoptosis in HUVEC. Cell death was
      also induced by a blockade of RhoA function by exoenzyme C3. In addition,
      treatment of HUVEC with the RhoA kinase inhibitors Y-27632 and HA-1077 caused
      dose-dependent cell death. Y-27632 did not inhibit other well known survival
      pathways, such as NF-kappa B, ERK, and phosphatidylinositol 3-kinase/Akt.
      However, there was an increase in p53 protein level concomitant with Y-27632
      induced cell death. Unlike the apoptosis induced by TNF-alpha, which occurs only
      with inhibition of new protein synthesis, apoptosis induced by inhibitors of HMG
      CoA reductase, geranylgeranyltransferase, or RhoA kinase was blocked by
      cycloheximide. Our data indicate that inhibition of protein geranylgeranylation
      and RhoA pathways induce apoptosis in HUVEC and that induction of p53 or other
      proapoptotic proteins is required for this process.

PMID- 11839766
TI  - Different modes of hypertrophy in skeletal muscle fibers.
AB  - Skeletal muscles display a remarkable diversity in their arrangement of fibers
      into fascicles and in their patterns of innervation, depending on functional
      requirements and species differences. Most human muscle fascicles, despite their
      great length, consist of fibers that extend continuously from one tendon to the
      other with a single nerve endplate band. Other mammalian muscles have multiple
      endplate bands and fibers that do not insert into both tendons but terminate
      intrafascicularly. We investigated whether these alternate structural features
      may dictate different modes of cell hypertrophy in two mouse gracilis muscles, in
      response to expression of a muscle-specific insulin-like growth factor (IGF)-1
      transgene (mIGF-1) or to chronic exercise. Both hypertrophic stimuli
      independently activated GATA-2 expression and increased muscle cross-sectional
      area in both muscle types, with additive effects in exercising myosin light
      chain/mIGF transgenic mice, but without increasing fiber number. In singly
      innervated gracilis posterior muscle, hypertrophy was characterized by a greater
      average diameter of individual fibers, and centralized nuclei. In contrast,
      hypertrophic gracilis anterior muscle, which is multiply innervated, contained
      longer muscle fibers, with no increase in average diameter, or in centralized
      nuclei. Different modes of muscle hypertrophy in domestic and laboratory animals
      have important implications for building appropriate models of human
      neuromuscular disease.

PMID- 11839767
TI  - Serum response factor is crucial for actin cytoskeletal organization and focal
      adhesion assembly in embryonic stem cells.
AB  - The activity of serum response factor (SRF), an essential transcription factor in
      mouse gastrulation, is regulated by changes in actin dynamics. Using Srf(-/-)
      embryonic stem (ES) cells, we demonstrate that SRF deficiency causes impairments
      in ES cell spreading, adhesion, and migration. These defects correlate with
      defective formation of cytoskeletal structures, namely actin stress fibers and
      focal adhesion (FA) plaques. The FA proteins FA kinase (FAK), beta1-integrin,
      talin, zyxin, and vinculin were downregulated and/or mislocalized in ES cells
      lacking SRF, leading to inefficient activation of the FA signaling kinase FAK.
      Reduced overall actin expression levels in Srf(-/-) ES cells were accompanied by
      an offset treadmilling equilibrium, resulting in lowered F-actin levels.
      Expression of active RhoA-V14 rescued F-actin synthesis but not stress fiber
      formation. Introduction of constitutively active SRF-VP16 into Srf(-/-) ES cells,
      on the other hand, strongly induced expression of FA components and F-actin
      synthesis, leading to a dramatic reorganization of actin filaments into stress
      fibers and lamellipodia. Thus, using ES cell genetics, we demonstrate for the
      first time the importance of SRF for the formation of actin-directed cytoskeletal
      structures that determine cell spreading, adhesion, and migration. Our findings
      suggest an involvement of SRF in cell migratory processes in multicellular
      organisms.

PMID- 11839768
TI  - Tpr is localized within the nuclear basket of the pore complex and has a role in
      nuclear protein export.
AB  - Tpr is a coiled-coil protein found near the nucleoplasmic side of the pore
      complex. Since neither the precise localization of Tpr nor its functions are well
      defined, we generated antibodies to three regions of Tpr to clarify these issues.
      Using light and EM immunolocalization, we determined that mammalian Tpr is
      concentrated within the nuclear basket of the pore complex in a distribution
      similar to Nup153 and Nup98. Antibody localization together with imaging of GFP
      Tpr in living cells revealed that Tpr is in discrete foci inside the nucleus
      similar to several other nucleoporins but is not present in intranuclear
      filamentous networks (Zimowska et al., 1997) or in long filaments extending from
      the pore complex (Cordes et al., 1997) as proposed. Injection of anti-Tpr
      antibodies into mitotic cells resulted in depletion of Tpr from the nuclear
      envelope without loss of other pore complex basket proteins. Whereas nuclear
      import mediated by a basic amino acid signal was unaffected, nuclear export
      mediated by a leucine-rich signal was retarded significantly. Nuclear injection
      of anti-Tpr antibodies in interphase cells similarly yielded inhibition of
      protein export but not import. These results indicate that Tpr is a nucleoporin
      of the nuclear basket with a role in nuclear protein export.

PMID- 11839769
TI  - Force transduction by Triton cytoskeletons.
AB  - Force-initiated signal transduction can occur either via membrane-based ionic
      mechanisms or through changes in cytoskeletal-matrix linkages. We report here the
      stretch-dependent binding of cytoplasmic proteins to Triton X-100 cytoskeletons
      of L-929 cells grown on collagen-coated silicone. Triton X-100-insoluble
      cytoskeletons were stretched by 10% and incubated with biotinylated cytoplasmic
      proteins. Analysis with two-dimensional gel electrophoresis showed stretch
      dependent binding of more than 10 cytoplasmic protein spots. Bound cytoplasmic
      proteins were purified by a photocleavable biotin tag and stretch-dependent
      binding of paxillin, focal adhesion kinase, and p130Cas was found, whereas the
      binding of vinculin was unchanged and actin binding decreased with stretch.
      Paxillin binding upon stretch was morphologically and biochemically similar in
      vitro and in vivo, that is, enhanced in the periphery and inhibited by the
      tyrosine phosphatase inhibitor, phenylarsine oxide. Thus, we suggest that
      transduction of matrix forces occurs through force-dependent conformation changes
      in the integrated cytoskeleton.

PMID- 11839770
TI  - Early/recycling endosomes-to-TGN transport involves two SNARE complexes and a
      Rab6 isoform.
AB  - The molecular mechanisms underlying early/recycling endosomes-to-TGN transport
      are still not understood. We identified interactions between the TGN-localized
      putative t-SNAREs syntaxin 6, syntaxin 16, and Vti1a, and two early/recycling
      endosomal v-SNAREs, VAMP3/cellubrevin, and VAMP4. Using a novel permeabilized
      cell system, these proteins were functionally implicated in the post-Golgi
      retrograde transport step. The function of Rab6a' was also required, whereas its
      closely related isoform, Rab6a, has previously been implicated in Golgi-to
      endoplasmic reticulum transport. Thus, our study shows that membrane exchange
      between the early endocytic and the biosynthetic/secretory pathways involves
      specific components of the Rab and SNARE machinery, and suggests that retrograde
      transport between early/recycling endosomes and the endoplasmic reticulum is
      critically dependent on the sequential action of two members of the Rab6
      subfamily.

PMID- 11839771
TI  - G protein-coupled receptor/arrestin3 modulation of the endocytic machinery.
AB  - Nonvisual arrestins (arr) modulate G protein-coupled receptor (GPCR)
      desensitization and internalization and bind to both clathrin (CL) and AP-2
      components of the endocytic coated pit (CP). This raises the possibility that
      endocytosis of some GPCRs may be a consequence of arr-induced de novo CP
      formation. To directly test this hypothesis, we examined the behavior of green
      fluorescent protein (GFP)-arr3 in live cells expressing beta2-adrenergic
      receptors and fluorescent CL. After agonist stimulation, the diffuse GFP-arr3
      signal rapidly became punctate and colocalized virtually completely with
      preexisting CP spots, demonstrating that activated complexes accumulate in
      previously formed CPs rather than nucleating new CP formation. After arr3
      recruitment, CP appeared larger: electron microscopy analysis revealed an
      increase in both CP number and in the occurrence of clustered CPs. Mutant arr3
      proteins with impaired binding to CL or AP-2 displayed reduced recruitment to
      CPs, but were still capable of inducing CP clustering. In contrast, though
      constitutively present in CPs, the COOH-terminal moiety of arr3, which contains
      CP binding sites but lacks receptor binding, did not induce CP clustering.
      Together, these results indicate that recruitment of functional arr3-GPCR
      complexes to CP is necessary to induce clustering. Latrunculin B or 16 degrees C
      blocked CP rearrangements without affecting arr3 recruitment to CP. These results
      and earlier studies suggest that discrete CP zones exist on cell surfaces, each
      capable of supporting adjacent CPs, and that the cortical actin membrane skeleton
      is intimately involved with both the maintenance of existing CPs and the
      generation of new structures.

PMID- 11839774
TI  - When the hunter becomes the hunted. By Caveman.

PMID- 11839772
TI  - Purification of pseudopodia from polarized cells reveals redistribution and
      activation of Rac through assembly of a CAS/Crk scaffold.
AB  - Initiation of cell migration requires morphological polarization with formation
      of a dominant leading pseudopodium and rear compartment. A molecular
      understanding of this process has been limited, due to the inability to
      biochemically separate the leading pseudopodium from the rear of the cell. Here
      we examine the spatio-temporal localization and activation of cytoskeletal
      associated signals in purified pseudopodia directed to undergo growth or
      retraction. Pseudopodia growth requires assembly of a p130Crk-associated
      substrate (CAS)/c-CrkII (Crk) scaffold, which facilitates translocation and
      activation of Rac1. Interestingly, Rac1 activation then serves as a positive
      feedback loop to maintain CAS/Crk coupling and pseudopodia extension. Conversely,
      disassembly of this molecular scaffold is critical for export and down regulation
      of Rac1 activity and induction of pseudopodia retraction. Surprisingly, the
      uncoupling of Crk from CAS during pseudopodium retraction is independent of
      changes in focal adhesion kinase activity and CAS tyrosine phosphorylation. These
      findings establish CAS/Crk as an essential scaffold for Rac1-mediated pseudopodia
      growth and retraction, and illustrate spatio-temporal segregation of cytoskeletal
      signals during cell polarization.

PMID- 11839773
TI  - PEX11 promotes peroxisome division independently of peroxisome metabolism.
AB  - The PEX11 peroxisomal membrane proteins are the only factors known to promote
      peroxisome division in multiple species. It has been proposed that PEX11 proteins
      have a direct role in peroxisomal fatty acid oxidation, and that they only affect
      peroxisome abundance indirectly. Here we show that PEX11 proteins are unique in
      their ability to promote peroxisome division, and that PEX11 overexpression
      promotes peroxisome division in the absence of peroxisomal metabolic activity. We
      also observed that mouse cells lacking PEX11beta display reduced peroxisome
      abundance, even in the absence of peroxisomal metabolic substrates, and that
      PEX11beta(-/-) mice are partially deficient in two distinct peroxisomal metabolic
      pathways, ether lipid synthesis and very long chain fatty acid oxidation. Based
      on these and other observations, we propose that PEX11 proteins act directly in
      peroxisome division, and that their loss has indirect effects on peroxisome
      metabolism.

PMID- 11839775
TI  - The Rho GTPase family: a Racs to Wrchs story.

PMID- 11839776
TI  - Protein phosphatase 1--targeted in many directions.
AB  - Protein phosphatase 1 (PP1) is a major eukaryotic protein serine/threonine
      phosphatase that regulates an enormous variety of cellular functions through the
      interaction of its catalytic subunit (PP1c) with over fifty different established
      or putative regulatory subunits. Most of these target PP1c to specific
      subcellular locations and interact with a small hydrophobic groove on the surface
      of PP1c through a short conserved binding motif--the RVxF motif--which is often
      preceded by further basic residues. Weaker interactions may subsequently enhance
      binding and modulate PP1 activity/specificity in a variety of ways. Several
      putative targeting subunits do not possess an RVxF motif but nevertheless
      interact with the same region of PP1c. In addition, several 'modulator' proteins
      bind to PP1c but do not possess a domain targeting them to a specific location.
      Most are potent inhibitors of PP1c and possess at least two sites for interaction
      with PP1c, one of which is identical or similar to the RVxF motif. Regulation of
      PP1c in response to extracellular and intracellular signals occurs mostly through
      changes in the levels, conformation or phosphorylation status of targeting
      subunits. Understanding of the mode of action of PP1c complexes may facilitate
      development of drugs that target particular PP1c complexes and thereby modulate
      the phosphorylation state of a very limited subset of proteins.

PMID- 11839777
TI  - Regulation of protrusive and contractile cell-matrix contacts.
AB  - The extracellular matrix is vital for tissue organisation in multicellular
      organisms. Cells attach to the extracellular matrix at discrete points on the
      cell surface, termed cell-matrix contacts. In general molecular terms, these
      contacts are assembled from large multiprotein complexes. However, many forms of
      matrix contacts can be distinguished by microscopy or by biochemical criteria,
      and these fulfil a diverse range of roles associated with cell adhesion,
      guidance, migration, matrix assembly, differentiation and survival. Two major
      functional categories are the protrusive and contractile matrix contacts. I
      describe contexts for the formation of protrusive or contractile contacts and
      discuss recent information on the molecular processes by which these contacts are
      specified, coordinated and regulated at a cellular level.

PMID- 11839779
TI  - The yeast ADP-ribosylation factor GAP, Gcs1p, is involved in maintenance of
      mitochondrial morphology.
AB  - Membrane trafficking is regulated, in part, by small GTP-binding proteins of the
      ADP-ribosylation factor (ARF) family. ARF function depends on the controlled
      binding and hydrolysis of GTP. In vitro, the GTPase activity of yeast ARF
      proteins can be stimulated by Gcs1p. Although Gcs1p was implicated in the
      regulation of retrograde transport from the Golgi to the ER and in actin
      cytoskeletal organization, its intracellular functions and distribution remain to
      be established. Following subcellular fractionation of yeast grown in rich
      medium, Gcs1p was localized in denser fractions than it was in cells grown in
      minimal medium. In yeast grown in rich or minimal medium, Gcs1p was distributed
      over the cytoplasm in a fine punctate pattern with more concentrated staining in
      the perinuclear regions. Overexpressed Gcs1p in yeast was localized partially
      with mitochondria and partially in perinuclear structures close to mitochondria.
      The Gcs1p PH-domain was required for localization in mitochondria but not for the
      perinuclear region. Transport of carboxypeptidase Y and invertase was not
      significantly altered by disruption of the gcs1 gene. This mutation did, however,
      reduce mitochondrial lateral distribution and branching when yeast were grown in
      rich medium. In yeast overexpressing Gcs1p, mitochondrial morphology was
      aberrant, with unbranched tubules and large spherical structures. We suggest that
      Gcs1p may be involved in the maintenance of mitochondrial morphology, possibly
      through organizing the actin cytoskeleton in Saccharomyces.

PMID- 11839778
TI  - Dual role for TWEAK in angiogenic regulation.
AB  - Angiogenic regulators modulate endothelial cell functions, including
      proliferation, migration, secretion, and adhesion, through their action on
      endothelial cells or other cell types. TWEAK, a novel member of the tumor
      necrosis factor family, appears to be a pro-angiogenic agent on the basis of
      previous studies demonstrating its ability to induce interleukin-8 production by
      epithelial tumor lines, stimulate proliferation of human vascular cell types and
      neovascularization in rat corneas. Here, we further characterized the angiogenic
      potential of TWEAK, revealing a dual role for TWEAK as an angiogenic regulator.
      We demonstrate that TWEAK is a potent inducer of endothelial cell survival and
      cooperates with basic fibroblast growth factor to induce the proliferation and
      migration of human endothelial cells and morphogenesis of capillary lumens. In
      contrast, TWEAK antagonizes the morphogenic response of endothelial cells to
      vascular endothelial growth factor (VEGF) without inhibiting VEGF-induced
      survival or proliferation. Thus, our observations suggest that TWEAK may
      differentially regulate microvascular growth, remodeling and/or maintenance in
      vivo, depending upon the angiogenic context.

PMID- 11839780
TI  - NCAM regulates cell motility.
AB  - Cell migration is required during development of the nervous system. The
      regulatory mechanisms for this process, however, are poorly elucidated. We show
      here that expression of or exposure to the neural cell adhesion molecule (NCAM)
      strongly affected the motile behaviour of glioma cells independently of
      homophilic NCAM interactions. Expression of the transmembrane 140 kDa isoform of
      NCAM (NCAM-140) caused a significant reduction in cellular motility, probably
      through interference with factors regulating cellular attachment, as NCAM-140
      expressing cells exhibited a decreased attachment to a fibronectin substratum
      compared with NCAM-negative cells. Ectopic expression of the cytoplasmic part of
      NCAM-140 also inhibited cell motility, presumably via the non-receptor tyrosine
      kinase p59(fyn) with which NCAM-140 interacts. Furthermore, we showed that the
      extracellular part of NCAM acted as a paracrine inhibitor of NCAM-negative cell
      locomotion through a heterophilic interaction with a cell-surface receptor. As we
      showed that the two N-terminal immunoglobulin modules of NCAM, which are known to
      bind to heparin, were responsible for this inhibition, we presume that this
      receptor is a heparan sulfate proteoglycan. A model for the inhibitory effect of
      NCAM is proposed, which involves competition between NCAM and extracellular
      components for the binding to membrane-associated heparan sulfate proteoglycan.

PMID- 11839781
TI  - In budding yeast, contraction of the actomyosin ring and formation of the primary
      septum at cytokinesis depend on each other.
AB  - Saccharomyces cerevisiae chs2 mutants are unable to synthesize primary septum
      chitin, and myo1 mutants cannot construct a functional contractile ring. The
      morphology of the two mutants, as observed by electron microscopy, is very
      similar. In both cases, neither an invagination of the plasma membrane, which
      normally results from contraction of the actomyosin ring, nor generation of a
      chitin disc, the primary septum, is observed. Rather, both mutants are able to
      complete cytokinesis by an abnormal process in which lateral walls thicken
      gradually and finally meet over an extended region, giving rise to a thick septum
      lacking the normal trilaminar structure and often enclosing lacunae. Defects in
      chs2 or myo1 strains were not aggravated in a double mutant, an indication that
      the corresponding proteins participate in a common process. In contrast, in a
      chs3 background the chs2 mutation is lethal and the myo1 defect is greatly
      worsened, suggesting that the synthesis of chitin catalyzed by chitin synthase
      III is necessary for the functionality of the remedial septa. Both chs2 and myo1
      mutants show abnormalities in budding pattern and a decrease in the level of
      certain proteins associated with budding, such as Bud3p, Bud4p and Spa2p. The
      possible reasons for these phenotypes and for the interdependence between
      actomyosin ring contraction and primary septum formation are discussed.

PMID- 11839782
TI  - Active EGF receptors have limited access to PtdIns(4,5)P(2) in endosomes:
      implications for phospholipase C and PI 3-kinase signaling.
AB  - Although prolonged cell signaling is attenuated by internalization and
      downregulation of active receptors, it is now appreciated that many receptors
      continue to signal in intracellular compartments. Employing enhanced green
      fluorescent protein fusion probes, we have investigated the hypothesis that
      multiple signaling pathways are affected by the differential trafficking of
      membrane substrates such as PtdIns(4,5)P(2). A phosphotyrosine-specific probe,
      but not a PtdIns(4,5)P(2)-specific probe, colocalized with internalized EGF as
      well as transferrin in EGF-stimulated living cells expressing autophosphorylation
      competent EGF receptors. Neither probe colocalized with transferrin in the
      absence of EGF, demonstrating that the reduced level of accessible
      PtdIns(4,5)P(2) in endosomes is constitutive. Finally, a PtdIns(3,4,5)P(3)
      specific probe, which monitors phosphorylation of PtdIns(4,5)P(2) by
      phosphoinositide 3-kinases, was recruited to the plasma membrane but not to EGF-
      or transferrin-containing endosomes in response to EGF stimulation. These results
      suggest that while many internalized receptors continue to engage intracellular
      enzymes, the phospholipase C and phosphoinositide 3-kinase signaling pathways are
      abrogated by the constitutive lack of accessible PtdIns(4,5)P(2) in endosomes.

PMID- 11839783
TI  - Increase of cAMP upon release from prophase arrest in surf clam oocytes.
AB  - Surf clam (Spisula solidissima) oocytes are spawned at the prophase I stage of
      meiosis, and they remain arrested at this stage until fertilization. Full oocyte
      meiosis reinitiation, first evidenced by germinal vesicle breakdown (GVBD), may
      be induced by artificial activators mimicking sperm, such as high K(+) or
      serotonin. Previous reports indicated that treatments thought to increase the
      level of oocyte cAMP inhibited sperm- or serotonin-induced, but not KCl-induced,
      GVBD in clam oocytes. These observations extend the well known requirement for a
      drop in oocyte cAMP levels in mammalian, amphibian or starfish oocytes and
      support the view that such a drop is universally important throughout the animal
      kingdom. We have re-examined the cAMP dependency of GVBD in clam oocytes and
      found that various treatments that raise oocyte cAMP levels did not,
      surprisingly, affect either KCl- or serotonin-induced GVBD. Such treatments,
      however, inhibited GVBD upon insemination of the oocytes, but this was due to the
      failure of sperm to fuse/penetrate the oocytes; thus, it was not an inhibition of
      oocyte activation as such. Direct measurements of oocyte cAMP levels after
      activation by serotonin, KCl or sperm showed that, contrary to expectations,
      there is a rise in cAMP levels before GVBD. Using SQ22536, an adenylyl cyclase
      inhibitor, the increase in oocyte cAMP level was partly prevented and GVBD
      proceeded, but with a significant retardation, indicating that the normal cAMP
      rise facilitates GVBD. Our work sheds light on the diversity of upstream pathways
      leading to activation of MPF and provides a unique model whereby the onset of
      meiosis reinitiation is associated with an increase, not a decrease, in oocyte
      cAMP levels.

PMID- 11839784
TI  - Kinetics of HCMV immediate early mRNA expression in stably transfected
      fibroblasts.
AB  - Compelling evidence supports an intimate link in time and space between
      eukaryotic pre-mRNA synthesis and processing and nucleocytoplasmic transport of
      mature mRNA. In this study, we analyzed the kinetic behavior of these processes
      in a quantitative manner. We used FISH and confocal scanning laser microscopy to
      detect transcripts produced by an inducible human cytomegalovirus immediate early
      (HCMV-IE) expression system. Upon induction, a large amount of pre-mRNA
      accumulated in nuclear foci at or near their transcription sites and, at later
      time, throughout the nucleoplasm. Inhibition of RNA polymerase II activity
      resulted in a rapid decrease in the number of transcripts in the nuclear RNA foci
      (half time approximately two minutes), indicating that accumulated transcripts
      were rapidly spliced and then released. The dispersed nucleoplasmic transcripts
      exited the nucleus with a half time of approximately 10 minutes. Both processes
      were temperature dependent, suggesting that mRNA export is an active process. RNA
      polymerase II activation revealed that production of mature HCMV IE mRNAs
      required less than five minutes. Transcripts radiated from the gene at an average
      speed of approximately 0.13 microm(2)/sec from this time on. Thus, it appears
      that these processes are tightly linked in time and space, with the splicing
      reaction as a rate-limiting factor.

PMID- 11839785
TI  - Transient pluripotent cell populations during primitive ectoderm formation:
      correlation of in vivo and in vitro pluripotent cell development.
AB  - Formation and differentiation of a pluripotent cell population is central to
      mammalian development, and the isolation, identification and manipulation of
      human pluripotent cells is predicted to be of therapeutic use. Within the early
      mammalian embryo, two distinct populations of pluripotent cells have been
      described: the inner cell mass (ICM), which differentiates to form a second
      pluripotent cell populations, the primitive ectoderm. Indirect evidence suggests
      the existence of temporally distinct intermediate pluripotent cell populations as
      primitive ectoderm is formed. We coupled an in vitro model of primitive ectoderm
      formation (the transition of embryonic stem cells to early primitive ectoderm
      like (EPL) cells) with ddPCR-based techniques to identify three novel genes,
      Psc1, CRTR-1 and PRCE, that were expressed differently during pluripotent cell
      progression. Detailed mapping of these genes with Oct4, Rex1 and Fgf5 on
      pregastrulation embryos provided the first molecular evidence for the existence
      of successive, temporally distinct pluripotent cell populations in the embryo
      between the ICM and primitive ectoderm. No evidence was found for spatial
      heterogeneity within the Oct4(+) pool. The transition between populations
      correlated with morphological or developmental alterations in pluripotent cells
      in vivo. Genes that are temporally expressed during pluripotent cell progression
      may provide an opportunity for molecular discrimination of pluripotent cells at
      different stages of maturation in vivo and an understanding of the cellular
      origins and properties of pluripotent cell lines isolated from diverse sources.
      Furthermore, the strong correlation of gene expression demonstrated between EPL
      cell formation in vitro and primitive ectoderm formation in vivo validates EPL
      cells as a model for primitive ectoderm, thereby providing a model system for the
      investigation of pluripotent differentiation and an opportunity for directed
      differentiation of pluripotent cells to therapeutically useful cell populations.

PMID- 11839786
TI  - The cell cycle dependent mislocalisation of emerin may contribute to the Emery
      Dreifuss muscular dystrophy phenotype.
AB  - Emerin is the nuclear membrane protein defective in X-linked Emery-Dreifuss
      muscular dystrophy (X-EDMD). The majority of X-EDMD patients have no detectable
      emerin. However, there are cases that produce mutant forms of emerin, which can
      be used to study its function. Our previous studies have shown that the emerin
      mutants S54F, P183T, P183H, Del95-99, Del236-241 (identified in X-EDMD patients)
      are targeted to the nuclear membrane but to a lesser extent than wild-type
      emerin. In this paper, we have studied how the mislocalisation of these mutant
      emerins may affect nuclear functions associated with the cell cycle using flow
      cytometry and immunofluorescence microscopy. We have established that cells
      expressing the emerin mutant Del236-241 (a deletion in the transmembrane domain),
      which was mainly localised in the cytoplasm, exhibited an aberrant cell cycle
      length. Thereafter, by examining the intracellular localisation of endogenously
      expressed lamin A/C and exogenously expressed wild-type and mutant forms of
      emerin after a number of cell divisions, we determined that the mutant forms of
      emerin redistributed endogenous lamin A/C. The extent of lamin A/C redistribution
      correlated with the amount of EGFP-emerin that was mislocalised. The amount of
      EGFP-emerin mislocalized, in turn, was associated with alterations in the nuclear
      envelope morphology. The nuclear morphology and redistribution of lamin A/C was
      most severely affected in the cells expressing the emerin mutant Del236-241. It
      is believed that emerin is part of a novel nuclear protein complex consisting of
      the barrier-to-autointegration factor (BAF), the nuclear lamina, nuclear actin
      and other associated proteins. The data presented here show that lamin A/C
      localisation is dominantly directed by its interaction with certain emerin
      mutants and perhaps wild-type emerin as well. These results suggest that emerin
      links A-type lamins to the nuclear envelope and that the correct localisation of
      these nuclear proteins is important for maintaining cell cycle timing.

PMID- 11839787
TI  - The effect of galectin-1 on the differentiation of fibroblasts and myoblasts in
      vitro.
AB  - Normal murine dermal fibroblasts implanted into the muscles of the mdx mouse, a
      model for Duchenne muscular dystrophy, not only participate in new myofibre
      formation but also direct the expression of the protein dystrophin which is
      deficient in these mice. We have reported that the lectin galectin-1 is
      implicated in the conversion of dermal fibroblasts to muscle. In the current work
      we confirm the presence of galectin-1 in the medium used for conversion.
      Furthermore we report that exposure of clones of dermal fibroblasts to this
      lectin results in 100% conversion of the cells. Conversion was assessed by the
      expression within the cells of the muscle-specific cytoskeletal protein desmin.
      We also investigate the effects of galectin-1 on cells of the C2C12 mouse
      myogenic cell line and on primary mouse myoblasts. Exposing both transformed and
      primary myoblasts to the lectin resulted in an increase in fusion of cells to the
      terminally differentiated state in both types of cultures. Galectin-1 does not
      cause the myogenic conversion of murine muscle-derived fibroblasts.

PMID- 11839788
TI  - How nematode sperm crawl.
AB  - Sperm of the nematode, Ascaris suum, crawl using lamellipodial protrusion,
      adhesion and retraction, a process analogous to the amoeboid motility of other
      eukaryotic cells. However, rather than employing an actin cytoskeleton to
      generate locomotion, nematode sperm use the major sperm protein (MSP). Moreover,
      nematode sperm lack detectable molecular motors or the battery of actin-binding
      proteins that characterize actin-based motility. The Ascaris system provides a
      simple 'stripped down' version of a crawling cell in which to examine the basic
      mechanism of cell locomotion independently of other cellular functions that
      involve the cytoskeleton. Here we present a mechanochemical analysis of crawling
      in Ascaris sperm. We construct a finite element model wherein (a) localized
      filament polymerization and bundling generate the force for lamellipodial
      extension and (b) energy stored in the gel formed from the filament bundles at
      the leading edge is subsequently used to produce the contraction that pulls the
      rear of the cell forward. The model reproduces the major features of crawling
      sperm and provides a framework in which amoeboid cell motility can be analyzed.
      Although the model refers primarily to the locomotion of nematode sperm, it has
      important implications for the mechanics of actin-based cell motility.

PMID- 11839789
TI  - The scaffold protein IB1/JIP-1 controls the activation of JNK in rat stressed
      urothelium.
AB  - The c-Jun N-terminal kinase (JNK) is critical for cell survival, differentiation,
      apoptosis and tumorigenesis. This signalling pathway requires the presence of the
      scaffold protein Islet-Brain1/c-Jun N-terminal kinase interacting protein-1
      (IB1/JIP-1). Immunolabeling and in situ hybridisation of bladder sections showed
      that IB1/JIP-1 is expressed in urothelial cells. The functional role of IB1/JIP-1
      in the urothelium was therefore studied in vivo in a model of complete rat
      bladder outlet obstruction. This parietal stress, which is due to urine
      retention, reduced the content of IB1/JIP-1 in urothelial cells and consequently
      induced a drastic increase in JNK activity and AP-1 binding activity. Using a
      viral gene transfer approach, the stress-induced activation of JNK was prevented
      by overexpressing IB1/JIP-1. Conversely, the JNK activity was increased in
      urothelial cells where the IB1/JIP-1 content was experimentally reduced using an
      antisense RNA strategy. Furthermore, JNK activation was found to be increased in
      non-stressed urothelial cells of heterozygous mice carrying a selective
      disruption of the IB1/JIP-1 gene. These data established that mechanical stress
      in urothelial cells in vivo induces a robust JNK activation as a consequence of
      regulated expression of the scaffold protein IB1/JIP-1. This result highlights a
      critical role for that scaffold protein in the homeostasis of the urothelium and
      unravels a new potential target to regulate the JNK pathway in this tissue.

PMID- 11839790
TI  - RNA helicase p54 (DDX6) is a shuttling protein involved in nuclear assembly of
      stored mRNP particles.
AB  - Previously, we showed that an integral component of stored mRNP particles in
      Xenopus oocytes, Xp54, is a DEAD-box RNA helicase with ATP-dependent RNA
      unwinding activity. Xp54 belongs to small family of helicases (DDX6) that
      associate with mRNA molecules encoding proteins required for progress through
      meiosis. Here we describe the nucleocytoplasmic translocation of recombinant Xp54
      in microinjected oocytes and in transfected culture cells. We demonstrate that
      Xp54 is present in oocyte nuclei, its occurrence in both soluble and particle
      bound forms and its ability to shuttle between nucleus and cytoplasm.
      Translocation of Xp54 from the nucleus to the cytoplasm appears to be dependent
      on the presence of a leucine-rich nuclear export signal (NES) and is blocked by
      leptomycin B, a specific inhibitor of the CRM1 receptor pathway. However, the C
      terminal region of Xp54 can act to retain the protein in the cytoplasm of full
      grown oocytes and culture cells. Cytoplasmic retention of Xp54 is overcome by
      activation of transcription. That Xp54 interacts directly with nascent
      transcripts is shown by immunostaining of the RNP matrix of lampbrush chromosome
      loops and co-immunoprecipitation with de novo-synthesized RNA. However, we are
      unable to show that nuclear export of this RNA is affected by either treatment
      with leptomycin B or mutation of the NES. We propose that newly synthesized Xp54
      is regulated in its nucleocytoplasmic distribution: in transcriptionally
      quiescent oocytes it is largely restricted to the cytoplasm and, if imported into
      the nucleus, it is rapidly exported again by the CRM1 pathway. In
      transcriptionally active oocytes, it binds to a major set of nascent transcripts,
      accompanies mRNA sequences to the cytoplasm by an alternative export pathway and
      remains associated with masked mRNA until the time of translation activation at
      meiotic maturation and early embryonic cell division.

PMID- 11839791
TI  - Characterization of temperature-sensitive mutations in the yeast syntaxin 1
      homologues Sso1p and Sso2p, and evidence of a distinct function for Sso1p in
      sporulation.
AB  - The duplicated genes SSO1 and SSO2 encode yeast homologues of syntaxin 1 and
      perform an essential function during fusion of secretory vesicles at the plasma
      membrane. We have used in vitro mutagenesis to obtain a temperature-sensitive
      SSO2 allele, sso2-1, in which a conserved arginine has been changed to a lysine.
      A yeast strain that lacks SSO1 and carries the sso2-1 allele ceases growth and
      accumulates secretory vesicles at the restrictive temperature. Interestingly, the
      strain also has a pronounced phenotype at the permissive temperature, causing a
      defect in bud neck closure that prevents separation of mother and daughter cells.
      The same mutation was introduced into SSO1, producing the sso1-1 allele, which
      also has a temperature-sensitive phenotype, although less pronounced than sso2-1.
      A screen for high copy number suppressors of sso2-1 yielded three genes that are
      involved in the terminal step of secretion: SNC1, SNC2 and SEC9. The sso1-1
      mutation interacts synthetically with a disruption of the MSO1 gene, which
      encodes a Sec1p interacting protein. Interestingly, we further found that both
      MSO1 and SSO1, but not SSO2, are required for sporulation. This difference is not
      due to differential expression, since SSO2 expressed from the SSO1 promoter
      failed to restore sporulation. We conclude that a functional difference exists
      between the Sso1 and Sso2 proteins, with the former being specifically required
      during sporulation.

PMID- 11839792
TI  - Three proteins required for early steps in the protein secretory pathway also
      affect nuclear envelope structure and cell cycle progression in fission yeast.
AB  - The Ran GTPase is an essential protein that has multiple functions in eukaryotic
      cells. Fission yeast cells in which Ran is misregulated arrest after mitosis with
      condensed, unreplicated chromosomes and abnormal nuclear envelopes. The fission
      yeast sns mutants arrest with a similar cell cycle block and interact genetically
      with the Ran system. sns-A10, sns-B2 and sns-B9 have mutations in the fission
      yeast homologues of S. cerevisiae Sar1p, Sec31p and Sec53p, respectively, which
      are required for the early steps of the protein secretory pathway. The three sns
      mutants accumulate a normally secreted protein in the endoplasmic reticulum (ER),
      have an increased amount of ER membrane, and the ER/nuclear envelope lumen is
      dilated. Neither a post-ER block in the secretory pathway, nor ER proliferation
      caused by overexpression of an integral ER membrane protein, results in a cell
      cycle-specific defect. Therefore, the arrest seen in sns-A10, sns-B2 and sns-B9
      is most likely due to nuclear envelope defects that render the cells unable to re
      establish the interphase organization of the nucleus after mitosis. As a
      consequence, these mutants are unable to decondense their chromosomes or to
      initiate of the next round of DNA replication.

PMID- 11839794
TI  - Actin-based motor properties of native myosin VIIa.
AB  - Myosin VIIa has critical roles in the inner ear and the retina. To help
      understand how this protein functions, native myosin VIIa was tested for
      mechanoenzymatic properties. Myosin VIIa was immunoprecipitated from retinal
      tissue and found to be associated with calmodulin in a Ca(2+)-sensitive manner.
      Myosin VIIa Mg-ATPase activity was detected; in the absence of Ca(2+) (i.e. with
      bound calmodulin), it was stimulated by f-actin with a K(cat) of 4.3 s(-1) and
      with 7 microM actin required for half-maximal activity. In a sliding filament
      motility assay, myosin VIIa moved actin filaments with a velocity of 190 nm s(
      1). These results demonstrate that myosin VIIa is a calmodulin-binding protein
      and a bona fide actin-based motor.

PMID- 11839793
TI  - Rho GTPases link cytoskeletal rearrangements and activation processes induced via
      the tetraspanin CD82 in T lymphocytes.
AB  - Activation of T lymphocytes requires the engagement of the T-cell receptor and
      costimulation molecules through cell-to-cell contacts. The tetraspanin CD82 has
      previously been shown to act as a cytoskeleton-dependent costimulation molecule.
      We show here that CD82 engagement leads to the tyrosine phosphorylation and
      association of both the Rho GTPases guanosine exchange factor Vav1 and adapter
      protein SLP76, suggesting that Rho GTPases participate in CD82 signaling. Indeed,
      broad inactivation of all Rho GTPases, or a specific blockade of RhoA, Rac1 or
      Cdc42, inhibited the morphological changes linked to CD82 engagement but failed
      to modulate the inducible association of CD82 with the actin network. Rho GTPase
      inactivation, as well as actin depolymerization, reduced the ability of CD82 to
      phosphorylate Vav and SLP76 and to potentiate the phosphorylation of two early
      TcR signaling intermediates: the tyrosine kinases ZAP70 and membrane adapter LAT.
      Taken together, this suggests that an amplification loop, via early Vav and SLP76
      phosphorylations and Rho-GTPases activation, is initiated by CD82 association
      with the cytoskeleton, which permits cytoskeletal rearrangements and
      costimulatory activity. Moreover, the involvement of CD82 in the formation of the
      immunological synapse is strongly suggested by its accumulation at the site of
      TcR engagement. This novel link between a tetraspanin and the Rho GTPase cascade
      could explain why tetraspanins, which are known to form heterocomplexes, are
      involved in cell activation, adhesion, growth and metastasis.

PMID- 11839795
TI  - Interaction of Huntington disease protein with transcriptional activator Sp1.
AB  - Polyglutamine expansion causes Huntington disease (HD) and at least seven other
      neurodegenerative diseases. In HD, N-terminal fragments of huntingtin with an
      expanded glutamine tract are able to aggregate and accumulate in the nucleus.
      Although intranuclear huntingtin affects the expression of numerous genes, the
      mechanism of this nuclear effect is unknown. Here we report that huntingtin
      interacts with Sp1, a transcription factor that binds to GC-rich elements in
      certain promoters and activates transcription of the corresponding genes. In
      vitro binding and immunoprecipitation assays show that polyglutamine expansion
      enhances the interaction of N-terminal huntingtin with Sp1. In HD transgenic mice
      (R6/2) that express N-terminal-mutant huntingtin, Sp1 binds to the soluble form
      of mutant huntingtin but not to aggregated huntingtin. Mutant huntingtin inhibits
      the binding of nuclear Sp1 to the promoter of nerve growth factor receptor and
      suppresses its transcriptional activity in cultured cells. Overexpression of Sp1
      reduces the cellular toxicity and neuritic extension defects caused by
      intranuclear mutant huntingtin. These findings suggest that the soluble form of
      mutant huntingtin in the nucleus may cause cellular dysfunction by binding to Sp1
      and thus reducing the expression of Sp1-regulated genes.

PMID- 11839797
TI  - Set2 is a nucleosomal histone H3-selective methyltransferase that mediates
      transcriptional repression.
AB  - Recent studies of histone methylation have yielded fundamental new insights
      pertaining to the role of this modification in gene activation as well as in gene
      silencing. While a number of methylation sites are known to occur on histones,
      only limited information exists regarding the relevant enzymes that mediate these
      methylation events. We thus sought to identify native histone methyltransferase
      (HMT) activities from Saccharomyces cerevisiae. Here, we describe the biochemical
      purification and characterization of Set2, a novel HMT that is site-specific for
      lysine 36 (Lys36) of the H3 tail. Using an antiserum directed against Lys36
      methylation in H3, we show that Set2, via its SET domain, is responsible for
      methylation at this site in vivo. Tethering of Set2 to a heterologous promoter
      reveals that Set2 represses transcription, and part of this repression is
      mediated through the HMT activity of the SET domain. These results suggest that
      Set2 and methylation at H3 Lys36 play a role in the repression of gene
      transcription.

PMID- 11839796
TI  - Kin28 is found within TFIIH and a Kin28-Ccl1-Tfb3 trimer complex with
      differential sensitivities to T-loop phosphorylation.
AB  - Basal transcription factor TFIIH phosphorylates the RNA polymerase II (RNApII)
      carboxy-terminal domain (CTD) within the transcription initiation complex. The
      catalytic kinase subunit of TFIIH is a member of the cyclin-dependent kinase
      (Cdk) family, designated Kin28 in Saccharomyces cerevisiae and Cdk7 in higher
      eukaryotes. Together with TFIIH subunits cyclin H and Mat1, Cdk7 kinase is also
      found in a trimer complex known as Cdk activating kinase (CAK). A yeast trimer
      complex has not previously been identified, although a Kin28-Ccl1 dimer called
      TFIIK has been isolated as a breakdown product of TFIIH. Here we show that a
      trimeric complex of Kin28-Ccl1-Tfb3 exists in yeast extracts. Several Kin28 point
      mutants that are defective in CTD phosphorylation were created. Consistent with
      earlier studies, these mutants have no transcriptional defect in vitro. Like
      other Cdks, Kin28 is activated by phosphorylation on T162 of the T loop. Kin28
      T162 mutants have no growth defects alone but do demonstrate synthetic phenotypes
      when combined with mutant versions of the cyclin partner, Ccl1. Surprisingly,
      these phosphorylation site mutants appear to destabilize the association of the
      cyclin subunit within the context of TFIIH but not within the trimer complex.

PMID- 11839798
TI  - BAF53 forms distinct nuclear complexes and functions as a critical c-Myc
      interacting nuclear cofactor for oncogenic transformation.
AB  - The c-Myc oncoprotein functions as a transcription factor that can transform
      normal cells into tumor cells, as well as playing a direct role in normal cell
      proliferation. The c-Myc protein transactivates cellular promoters by recruiting
      nuclear cofactors to chromosomal sites through an N-terminal transactivation
      domain. We have previously reported the identification and functional
      characterization of four different c-Myc cofactors: TRRAP, hGCN5, TIP49, and
      TIP48. Here we present the identification and characterization of the actin
      related protein BAF53 as a c-Myc-interacting nuclear cofactor that forms distinct
      nuclear complexes. In addition to the human SWI/SNF-related BAF complex, BAF53
      forms a complex with TIP49 and TIP48 and a separate biochemically distinct
      complex containing TRRAP and a histone acetyltransferase which does not contain
      TIP60. Using deletion mutants of BAF53, we show that BAF53 is critical for c-Myc
      oncogenic activity. Our results indicate that BAF53 plays a functional role in c
      Myc-interacting nuclear complexes.

PMID- 11839799
TI  - A maternal Smad protein regulates early embryonic apoptosis in Xenopus laevis.
AB  - We identified cDNAs encoding the Xenopus Smad proteins most closely related to
      mammalian Smad8, and we present a functional analysis of this activity (also
      referred to recently as xSmad11). Misexpression experiments indicate that
      xSmad8(11) regulates pathways distinct from those regulated by the closely
      related xSmad1. Embryos that develop from eggs depleted of xSmad8(11) mRNA fail
      to gastrulate; instead, at the time of gastrulation, they initiate a widespread
      program of apoptosis, via a CPP32/caspase 3 pathway. Embryos that avoid this fate
      display gastrulation defects. Activation of apoptosis is rescued by expression of
      xSmad8(11) but not xSmad1. Our results demonstrate an embryonic requirement for
      Smad8(11) activity and show that a maternally derived Smad signaling pathway is
      required for gastrulation and for mediating a cell survival program during early
      embryogenesis. We suggest that xSmad8(11) functions as part of a maternally
      derived mechanism shown previously by others to monitor Xenopus early embryonic
      cell cycles.

PMID- 11839800
TI  - Yeast protein kinases and the RHO1 exchange factor TUS1 are novel components of
      the cell integrity pathway in yeast.
AB  - The PKC1-associated mitogen-activated protein (MAP) kinase pathway of
      Saccharomyces cerevisiae regulates cell integrity by controlling the actin
      cytoskeleton and cell wall synthesis. Activation of PKC1 occurs via the GTPase
      RHO1 and the kinase pair PKH1 and PKH2. Here we report that YPK1 and YPK2, an
      essential pair of homologous kinases and proposed downstream effectors of PKH and
      sphingolipids, are also regulators of the PKC1-controlled MAP kinase cascade. ypk
      mutants display random distribution of the actin cytoskeleton and severely
      reduced activation of the MAP kinase MPK1. Upregulation of the RHO1 GTPase switch
      or the PKC1 effector MAP kinase pathway suppresses the growth and actin defects
      of ypk cells. ypk lethality is also suppressed by overexpression of an
      uncharacterized gene termed TUS1. TUS1 is a novel RHO1 exchange factor that
      contributes to cell wall integrity-mediated modulation of RHO1 activity. Thus,
      TUS1 and the YPKs add to the growing complexity of RHO1 and PKC1 regulation in
      the cell integrity signaling pathway. Furthermore, our findings suggest that the
      YPKs are a missing link between sphingolipid signaling and the cell integrity
      pathway.

PMID- 11839801
TI  - Fine structure and activity of discrete RAG-HMG complexes on V(D)J recombination
      signals.
AB  - Two lymphoid cell-specific proteins, RAG-1 and RAG-2, initiate V(D)J
      recombination by introducing DNA breaks at recombination signal sequences (RSSs).
      Although the RAG proteins themselves bind and cleave DNA substrates containing
      either a 12-RSS or a 23-RSS, DNA-bending proteins HMG-1 and HMG-2 are known to
      promote these processes, particularly with 23-RSS substrates. Using in-gel
      cleavage assays and DNA footprinting techniques, I analyzed the catalytic
      activity and protein-DNA contacts in discrete 12-RSS and 23-RSS complexes
      containing the RAG proteins and either HMG-1 or HMG-2. I found that both the
      cleavage activity and the pattern of protein-DNA contacts in RAG-HMG complexes
      assembled on 12-RSS substrates closely resembled those obtained from analogous 12
      RSS complexes lacking HMG protein. In contrast, 23-RSS complexes containing both
      RAG proteins and either HMG-1 or HMG-2 exhibited enhanced cleavage activity and
      displayed an altered distribution of cleavage products compared to 23-RSS
      complexes containing only RAG-1 and RAG-2. Moreover, HMG-dependent heptamer
      contacts in 23-RSS complexes were observed. The protein-DNA contacts in RAG-RSS
      HMG complexes assembled on 12-RSS or 23-RSS substrates were strikingly similar at
      comparable positions, suggesting that the RAG proteins mediate HMG-dependent
      heptamer contacts in 23-RSS complexes. Results of ethylation interference
      experiments suggest that the HMG protein is positioned 5' of the nonamer in 23
      RSS complexes, interacting largely with the side of the duplex opposite the one
      contacting the RAG proteins. Thus, HMG protein plays the dual role of bringing
      critical elements of the 23-RSS heptamer into the same phase as the 12-RSS to
      promote RAG binding and assisting in the catalysis of 23-RSS cleavage.

PMID- 11839802
TI  - Integrin alpha 2 beta 1 promotes activation of protein phosphatase 2A and
      dephosphorylation of Akt and glycogen synthase kinase 3 beta.
AB  - Serine/threonine kinase Akt is a downstream effector protein of
      phosphatidylinositol-3-kinase (PI-3K). Many integrins can function as positive
      modulators of the PI-3K/Akt pathway. Integrin alpha 2 beta 1 is a collagen
      receptor that has been shown to induce specific signals distinct from those
      activated by other integrins. Here, we found that, in contrast what was found for
      cells adherent to fibronectin, alpha 2 beta 1-mediated cell adhesion to collagen
      leads to dephosphorylation of Akt and glycogen synthase kinase 3 beta (GSK3 beta)
      and concomitantly to the induction of protein serine/threonine phosphatase 2A
      (PP2A) activity. PP2A activation can be inhibited by mutation in the alpha 2
      cytoplasmic domain and by a function-blocking anti-alpha 2 antibody. Akt can be
      coprecipitated with PP2A, and coexpression of Akt with PP2Ac (catalytic subunit)
      inhibits Akt kinase activity. Integrin alpha 2 beta 1-related activation of PP2A
      is dependent on Cdc42. These results indicate that cell adhesion to collagen
      modulates Akt activity via the alpha 2 beta 1-induced activation of PP2A.

PMID- 11839803
TI  - ARF differentially modulates apoptosis induced by E2F1 and Myc.
AB  - The ARF tumor suppressor participates in a p53-dependent apoptotic pathway that
      is stimulated in response to some oncogenic stimuli. The E2F1 transcription
      factor is a critical downstream target of the Rb tumor suppressor and, when
      active, can promote proliferation as well as apoptosis. The finding that E2F1
      transcriptionally regulates the ARF gene has led to the suggestion that ARF
      contributes to E2F1-induced apoptosis. Counter to this hypothesis, this study
      demonstrates not only that ARF is unnecessary for E2F1 to induce apoptosis but
      also that inactivation of ARF actually enhances the ability of E2F1 to promote
      apoptosis. Inactivation of ARF also cooperates with E2F1 activity to promote
      entry into the S phase of the cell cycle. This relationship between ARF and E2F1
      is demonstrated in transgenic epidermis in vivo and in mouse embryo fibroblast
      cultures in vitro. In contrast, the ability of Myc to induce apoptosis is
      diminished in the absence of ARF. E2F1 induces the accumulation of p53 in the
      absence of ARF, and this is associated with the phosphorylation of p53 on several
      residues. These findings demonstrate that ARF is a negative regulator of E2F1
      activity and is not required for E2F1-induced apoptosis.

PMID- 11839804
TI  - Transforming growth factor beta 1 induces apoptosis through cleavage of BAD in a
      Smad3-dependent mechanism in FaO hepatoma cells.
AB  - Transforming growth factor beta (TGF-beta) induces apoptosis in a variety of
      cells. We have previously shown that TGF-beta 1 rapidly induces apoptosis in the
      FaO rat hepatoma cell line. We have now studied the effect of TGF-beta 1 on the
      expression of different members of the Bcl-2 family in these cells. We observed
      no detectable changes in the steady-state levels of Bcl-2, Bcl-X(L), and Bax.
      However, TGF-beta 1 induced caspase-dependent cleavage of BAD at its N terminus
      to generate a 15-kDa truncated protein. Overexpression of the 15-kDa truncated
      BAD protein enhanced TGF-beta 1-induced apoptosis, whereas a mutant BAD resistant
      to caspase 3 cleavage blocked TGF-beta 1-induced apoptosis. Overexpression of
      Smad3 dramatically enhanced TGF-beta 1-induced cleavage of BAD and apoptosis,
      whereas antisense Smad3 blocked TGF-beta 1-induced apoptosis and BAD cleavage.
      These results suggest that TGF-beta 1 induces apoptosis through the cleavage of
      BAD in a Smad3-dependent mechanism.

PMID- 11839805
TI  - Functional analysis of yeast snoRNA and snRNA 3'-end formation mediated by
      uncoupling of cleavage and polyadenylation.
AB  - Many nuclear and nucleolar small RNAs are accumulated as nonpolyadenylated
      species and require 3'-end processing for maturation. Here, we show that several
      genes coding for box C/D and H/ACA snoRNAs and for the U5 and U2 snRNAs contain
      sequences in their 3' portions which direct cleavage of primary transcripts
      without being polyadenylated. Genetic analysis of yeasts with mutations in
      different components of the pre-mRNA cleavage and polyadenylation machinery
      suggests that this mechanism of 3"-end formation requires cleavage factor IA (CF
      IA) but not cleavage and polyadenylation factor activity. However, in vitro
      results indicate that other factors participate in the reaction besides CF IA.
      Sequence analysis of snoRNA genes indicated that they contain conserved motifs in
      their 3" noncoding regions, and mutational studies demonstrated their essential
      role in 3"-end formation. We propose a model in which CF IA functions in cleavage
      and polyadenylation of pre-mRNAs and, in combination with a different set of
      factors, in 3"-end formation of nonpolyadenylated polymerase II transcripts.

PMID- 11839806
TI  - The B-domain lysine patch of pRB is required for binding to large T antigen and
      release of E2F by phosphorylation.
AB  - Cell cycle-dependent, site-specific phosphorylation of the retinoblastoma
      protein, pRB, is mediated by cyclin-dependent kinases (CDKs) and regulates the
      binding of pRB to many proteins. We previously showed that the interaction of pRB
      with E2F on DNA was regulated by the accumulation of phosphate groups on pRB.
      Here we show that positively charged lysine residues in the B domain of pRB are
      necessary for the release of pRB from E2F on DNA following phosphorylation by
      cyclin E-cdk2 kinase. These lysine residues are also important in the binding of
      the simian virus 40 large T antigen (TAg) to pRB, and mutation of these lysines
      to arginines alters the dependency of the pRB-TAg interaction on phosphorylation
      of pRB.

PMID- 11839807
TI  - Mammalian selenoprotein in which selenocysteine (Sec) incorporation is supported
      by a new form of Sec insertion sequence element.
AB  - Selenocysteine (Sec), the 21st amino acid in protein, is encoded by UGA. The Sec
      insertion sequence (SECIS) element, which is the stem-loop structure present in
      3' untranslated regions (UTRs) of eukaryotic selenoprotein-encoding genes, is
      essential for recognition of UGA as a codon for Sec rather than as a stop signal.
      We now report the identification of a new eukaryotic selenoprotein, designated
      selenoprotein M (SelM). The 3-kb human SelM-encoding gene has five exons and is
      located on chromosome 22 but has not been correctly identified by either Celera
      or the public Human Genome Project. We characterized human and mouse SelM cDNA
      sequences and expressed the selenoprotein in various mammalian cell lines. The 3"
      UTR of the human, mouse, and rat SelM-encoding genes lacks a canonical SECIS
      element. Instead, Sec is incorporated in response to a conserved mRNA structure,
      in which cytidines are present in place of the adenosines previously considered
      invariant. Substitution of adenosines for cytidines did not alter Sec
      incorporation; however, other mutant structures did not support selenoprotein
      synthesis, demonstrating that this new form of SECIS element is functional. SelM
      is expressed in a variety of tissues, with increased levels in the brain. It is
      localized to the perinuclear structures, and its N-terminal signal peptide is
      necessary for protein translocation.

PMID- 11839808
TI  - Apoptotic regulation by the Crk adapter protein mediated by interactions with
      Wee1 and Crm1/exportin.
AB  - The adapter protein Crk contains an SH2 domain and two SH3 domains. Through
      binding of particular ligands to the SH2 domain and the N-terminal SH3 domain,
      Crk has been implicated in a number of signaling processes, including regulation
      of cell growth, cell motility, and apoptosis. We report here that the C-terminal
      SH3 domain, never shown to bind any specific signaling molecules, contains a
      binding site for the nuclear export factor Crm1. We find that a mutant Crk
      protein, deficient in Crm1 binding, promotes apoptosis. Moreover, this nuclear
      export sequence mutant [NES(-) Crk] interacts strongly, through its SH2 domain,
      with the nuclear tyrosine kinase, Wee1. Collectively, these data suggest that a
      nuclear population of Crk bound to Wee1 promotes apoptotic death of mammalian
      cells.

PMID- 11839810
TI  - Ultrastructural cartilage abnormalities in MIA/CD-RAP-deficient mice.
AB  - MIA/CD-RAP is a small, soluble protein secreted from malignant melanoma cells and
      from chondrocytes. Recent evidence has identified MIA/CD-RAP as the prototype of
      a small family of extracellular proteins adopting an SH3 domain-like fold. It is
      thought that interaction between MIA/CD-RAP and specific epitopes in
      extracellular matrix proteins regulates the attachment of tumor cells and
      chondrocytes. In order to study the consequences of MIA/CD-RAP deficiency in
      vivo, we generated mice with a targeted gene disruption. The complete absence of
      MIA/CD-RAP mRNA and protein expression was demonstrated by reverse transcriptase,
      Western blot analysis, and enzyme-linked immunosorbent assay measurements of
      whole-embryo extracts. MIA(-/-) mice were viable and developed normally, and
      histological examination of the organs by means of light microscopy revealed no
      major abnormalities. In contrast, electron microscopic studies of cartilage
      composition revealed subtle defects in collagen fiber density, diameter, and
      arrangement, as well as changes in the number and morphology of chondrocytic
      microvilli. Taken together, our data indicate that MIA/CD-RAP is essentially
      required for formation of the highly ordered ultrastructural fiber architecture
      in cartilage and may have a role in regulating chondrocyte matrix interactions.

PMID- 11839809
TI  - Genetic ablation of the CDP/Cux protein C terminus results in hair cycle defects
      and reduced male fertility.
AB  - Murine CDP/Cux, a homologue of the Drosophila Cut homeoprotein, modulates the
      promoter activity of cell cycle-related and cell-type-specific genes. CDP/Cux
      interacts with histone gene promoters as the DNA binding subunit of a large
      nuclear complex (HiNF-D). CDP/Cux is a ubiquitous protein containing four
      conserved DNA binding domains: three Cut repeats and a homeodomain. In this
      study, we analyzed genetically targeted mice (Cutl1(tm2Ejn), referred to as Delta
      C) that express a mutant CDP/Cux protein with a deletion of the C terminus,
      including the homeodomain. In comparison to the wild-type protein, indirect
      immunofluorescence showed that the mutant protein exhibited significantly reduced
      nuclear localization. Consistent with these data, DNA binding activity of HiNF-D
      was lost in nuclear extracts derived from mouse embryonic fibroblasts (MEFs) or
      adult tissues of homozygous mutant (Delta C(-/-)) mice, indicating the functional
      loss of CDP/Cux protein in the nucleus. No significant difference in growth
      characteristics or total histone H4 mRNA levels was observed between wild-type
      and Delta C(-/-) MEFs in culture. However, specific histone genes (H4.1 and H1)
      containing CDP/Cux binding sites have reduced expression levels in homozygous
      mutant MEFs. Stringent control of growth and differentiation appears to be
      compromised in vivo. Homozygous mutant mice have stunted growth (20 to 50% weight
      reduction), a high postnatal death rate of 60 to 70%, sparse abnormal coat hair,
      and severely reduced fertility. The deregulated hair cycle and severely
      diminished fertility in Cutl1(tm2Ejn/tm2Ejn) mice suggest that CDP/Cux is
      required for the developmental control of dermal and reproductive functions.

PMID- 11839811
TI  - Chromosomal integration of retinoic acid response elements prevents cooperative
      transcriptional activation by retinoic acid receptor and retinoid X receptor.
AB  - All-trans-retinoic acid receptors (RAR) and 9-cis-retinoic acid receptors (RXR)
      are nuclear receptors known to cooperatively activate transcription from retinoid
      regulated promoters. By comparing the transactivating properties of RAR and RXR
      in P19 cells using either plasmid or chromosomal reporter genes containing the
      mRAR beta 2 gene promoter, we found contrasting patterns of transcriptional
      regulation in each setting. Cooperativity between RXR and RAR occurred at all
      times with transiently introduced promoters, but was restricted to a very early
      stage (<3 h) for chromosomal promoters. This time-dependent loss of cooperativity
      was specific for chromosomal templates containing two copies of a retinoid
      responsive element (RARE) and was not influenced by the spacing between the two
      RAREs. This loss of cooperativity suggested a delayed acquisition of RAR full
      transcriptional competence because (i) cooperativity was maintained at RAR ligand
      subsaturating concentrations, (ii) overexpression of SRC-1 led to loss of
      cooperativity and even to strong repression of chromosomal templates activity,
      and (iii) loss of cooperativity was observed when additional cis-acting response
      elements were activated. Surprisingly, histone deacetylase inhibitors
      counteracted this loss of cooperativity by repressing partially RAR-mediated
      activation of chromosomal promoters. Loss of cooperativity was not correlated to
      local histone hyperacetylation or to alteration of constitutive RNA polymerase II
      (RNAP) loading at the promoter region. Unexpectedly, RNAP binding to transcribed
      regions was correlated to the RAR activation state as well as to acetylation
      levels of histones H3 and H4, suggesting that RAR acts at the mRAR beta promoter
      by triggering the switch from an RNA elongation-incompetent RNAP form towards an
      RNA elongation-competent RNAP.

PMID- 11839812
TI  - Mouse lymphoid cell line selected to have high immunoglobulin promoter activity.
AB  - Immunoglobulin variable region promoters are predominantly B-cell specific, but
      the molecular basis for this specificity has not been elucidated. To further
      understand how B-cell-specific immunoglobulin promoter expression is mediated,
      the murine lymphoid cell line 2017 was engineered to express the green
      fluorescent protein under the control of an immunoglobulin heavy chain promoter
      and selected for high activity using multiple rounds of fluorescence-activated
      cell sorting. Rare clones with intense and stable immunoglobulin promoter
      activity were isolated. Transient transfection experiments demonstrated that two
      different immunoglobulin promoters and two other B-cell-specific promoters have
      higher activities in the selected cell lines relative to the parental line and to
      the non-cell-type-specific histone H2B promoter. The increased immunoglobulin
      activity required nucleotide residues downstream of the transcription initiation
      site which were also important for maximal activity in B cells and which were
      conserved in other B-cell-specific promoters. Unlike the unselected cells, the
      2017 variants also showed activation of their endogenous immunoglobulin heavy
      chain variable regions.

PMID- 11839813
TI  - Genetic dissection of cadherin function during nephrogenesis.
AB  - The distinct expression of R-cadherin in the induced aggregating metanephric
      mesenchyme suggests that it may regulate the mesenchymal-epithelial transition
      during kidney development. To address whether R-cadherin is required for kidney
      ontogeny, R-cadherin-deficient mice were generated. These mice appeared to be
      healthy and were fertile, demonstrating that R-cadherin is not essential for
      embryogenesis. The only kidney phenotype of adult mutant animals was the
      appearance of dilated proximal tubules, which was associated with an accumulation
      of large intracellular vacuoles. Morphological analysis of nephrogenesis in R
      cadherin(-/-) mice in vivo and in vitro revealed defects in the development of
      both ureteric bud-derived cells and metanephric mesenchyme-derived cells. First,
      the morphology and organization of the proximal parts of the ureteric bud
      epithelium were altered. Interestingly, these morphological changes correlated
      with an increased rate of apoptosis and were further supported by perturbed
      branching and patterning of the ureteric bud epithelium during in vitro
      differentiation. Second, during in vitro studies of mesenchymal-epithelial
      conversion, significantly fewer epithelial structures developed from R-cadherin(
      /-) kidneys than from wild-type kidneys. These data suggest that R-cadherin is
      functionally involved in the differentiation of both mesenchymal and epithelial
      components during metanephric kidney development. Finally, to investigate whether
      the redundant expression of other classic cadherins expressed in the kidney could
      explain the rather mild kidney defects in R-cadherin-deficient mice, we
      intercrossed R-cadherin(-/-) mice with cadherin-6(-/-), P-cadherin(-/-), and N
      cadherin(+/-) mice. Surprisingly, however, in none of the compound knockout
      strains was kidney development affected to a greater extent than within the
      individual cadherin knockout strains.

PMID- 11839814
TI  - Embryonic lethality caused by apoptosis during gastrulation in mice lacking the
      gene of the ADP-ribosylation factor-related protein 1.
AB  - ADP-ribosylation factor (ARF)-related protein 1 (ARFRP1) is a membrane-associated
      GTPase with significant similarity to the family of ARFs. We have recently shown
      that ARFRP1 interacts with the Sec7 domain of the ARF-specific guanine nucleotide
      exchange factor Sec7-1/cytohesin and inhibits the ARF/Sec7-dependent activation
      of phospholipase D in a GTP-dependent manner. In order to further analyze the
      function of ARFRP1, we cloned the mouse Arfrp1 gene and generated Arfrp1 null
      mutant mice by gene targeting in embryonic stem cells. Heterozygous Arfrp1
      mutants developed normally, whereas homozygosity for the mutant allele led to
      embryonic lethality. Cultured homozygous Arfrp1 null-mutant blastocysts were
      indistinguishable from wild-type blastocysts. In vivo, they implanted and formed
      egg cylinder stage embryos that appeared normal until day 5. Between embryonic
      days 6 and 7, however, apoptotic cell death of epiblast cells occurred in the
      embryonic ectoderm during gastrulation, as was shown by histological analysis
      combined with terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end
      labeling. Epiblast cells that would normally differentiate to mesodermal cells
      detached from the ectodermal cell layer and were dispersed into the proamniotic
      cavity. In contrast, the development of extraembryonic structures appeared
      unaffected. Our results demonstrate that ARFRP1 is necessary for early embryonic
      development during gastrulation.

PMID- 11839815
TI  - Conditional loss of Nkx3.1 in adult mice induces prostatic intraepithelial
      neoplasia.
AB  - The homeodomain-containing transcription factor NKX3.1 is a putative prostate
      tumor suppressor that is expressed in a largely prostate-specific and androgen
      regulated manner. Loss of NKX3.1 protein expression is common in human prostate
      carcinomas and prostatic intraepithelial neoplasia (PIN) lesions and correlates
      with tumor progression. Disruption of the murine Nkx3.1 gene results in defects
      in prostate branching morphogenesis, secretions, and growth. To more closely
      mimic the pattern of NKX3.1 loss that occurs in human prostate tumors, we have
      used Cre- and loxP-mediated recombination to delete the Nkx3.1 gene in the
      prostates of adult transgenic mice. Conditional deletion of one or both alleles
      of Nkx3.1 leads to the development of preinvasive lesions that resemble PIN. The
      pattern of expression of several biomarkers (Ki-67, E-cadherin, and high
      molecular-weight cytokeratins) in these PIN lesions resembled that observed in
      human cases of PIN. Furthermore, PIN foci in mice with conditional deletion of a
      single Nkx3.1 allele lose expression of the wild-type allele. Our results support
      the role of NKX3.1 as a prostate tumor suppressor and indicate a role for this
      gene in tumor initiation.

PMID- 11839816
TI  - Mouse Pop1 is required for muscle regeneration in adult skeletal muscle.
AB  - Popeye (Pop) genes are a novel gene family encoding putative transmembrane
      proteins predominantly present in striated and smooth muscle cells. In this
      study, a null mutation of Pop1 was generated by replacing the first coding exon
      of the Pop1 gene with the lacZ reporter gene. Homozygous mice lacking Pop1 were
      fertile and had a normal life span without any apparent phenotype. LacZ staining
      of tissues of heterozygous and homozygous Pop1-LacZ mice revealed strong
      expression in embryonic and fetal hearts. Pop1-LacZ was also expressed in the
      myotome and in myogenic progenitor cells within the limb and in smooth muscle
      cells of various organs. In the heart, Pop1-LacZ activity was downregulated
      postnatally in heterozygous mice but not in homozygous mice. Administration of
      the beta-adrenergic agonist isoproterenol led to a rapid increase in Pop1-LacZ
      activity in heterozygotes without induction at the transcriptional level,
      suggesting stabilization of the protein. No difference, however, was observed
      between homozygous and heterozygous mice in the ability to develop cardiac
      hypertrophy in response to isoproterenol. The capacity to regenerate skeletal
      muscle was tested after cardiotoxin injection into the hind limbs of hetero- and
      homozygous mice. In activated satellite cells of both genotypes, rapid activation
      of Pop1-LacZ expression was observed. In heterozygous animals, LacZ activity was
      only transiently elevated in muscle precursor cells undergoing fusion and in
      newly formed myotubes. In homozygotes, persistence of LacZ expression and a
      retarded ability to regenerate skeletal muscle were apparent, suggesting that
      Pop1 plays a role in muscle regeneration.

PMID- 11839817
TI  - Identification of Akt association and oligomerization domains of the Akt kinase
      coactivator TCL1.
AB  - Serine/threonine kinase Akt/protein kinase B, the cellular homologue of the
      transforming viral oncogene v-Akt, plays a central role in the regulation of cell
      survival and proliferation. We have previously demonstrated that the proto
      oncogene TCL1 is an Akt kinase coactivator. TCL1 binds to Akt and mediates the
      formation of oligomeric TCL1-Akt high-molecular-weight protein complexes in vivo.
      Within these protein complexes, Akt is preferentially phosphorylated and
      activated. The MTCP1/TCL1/TCL1b oncogene activation is the hallmark of human T
      cell prolymphocytic leukemia (T-PLL), a form of adult leukemia. In the present
      study, using a PCR-generated random TCL1 library combined with a yeast two-hybrid
      screening detecting loss of interaction, we identified D16 and I74 as amino acid
      residues mediating the association of TCL1 with Akt. Based on molecular modeling,
      we determined that the beta C-sheet of TCL1 is essential for TCL1
      homodimerization. Studies with mammalian overexpression systems demonstrated that
      both Akt association and oligomerization domains of TCL1 are distinct functional
      domains. In vitro kinase assays and overexpression experiments in mammalian cells
      demonstrated that both TCL1-Akt interaction and oligomerization of TCL1 were
      required for TCL1-induced Akt activation and substrate phosphorylation. Assays
      for mitochondrial permeability transition, nuclear translocation, and cell
      recovery demonstrated that both Akt association and homodimerization of TCL1 are
      similarly needed for the full function of TCL1 as an Akt kinase coactivator in
      vivo. The results demonstrate the structural basis of TCL1-induced activation of
      Akt, which causes human T-PLL.

PMID- 11839818
TI  - Phenotypic complementation establishes requirements for specific POU domain and
      generic transactivation function of Oct-3/4 in embryonic stem cells.
AB  - Transcription factors of the POU family govern cell fate through combinatorial
      interactions with coactivators and corepressors. The POU factor Oct-3/4 can
      define differentiation, dedifferentation, or self-renewal of pluripotent
      embryonic stem (ES) cells in a sensitive, dose-dependent manner (H. Niwa, J.-I.
      Miyazali, and A. G. Smith, Nat. Genet. 24:372-376, 2000). Here we have developed
      a complementation assay based on the ability of Oct-3/4 transgenes to rescue self
      renewal in conditionally null ES cells and used this to define which domains of
      Oct-3/4 are required to sustain the undifferentiated stem cell phenotype.
      Surprisingly, we found that molecules lacking either the N-terminal or C-terminal
      transactivation domain, though not both, can effectively replace full-length Oct
      3/4. Furthermore, a fusion of the heterologous transactivation domain of Oct-2 to
      the Oct-3/4 POU domain can also sustain self-renewal. Thus, the unique function
      of Oct-3/4 in ES cell propagation resides in combination of the specific POU
      domain with a generic proline-rich transactivation domain. Interestingly,
      however, Oct-3/4 target gene expression elicited by the N- and C-terminal
      transactivation domains is not identical, indicating that at least one class of
      genes activated by Oct-3/4 is not required for ES cell propagation.

PMID- 11839820
TI  - Loss of the zymogen granule protein syncollin affects pancreatic protein
      synthesis and transport but not secretion.
AB  - Syncollin is a small protein that is abundantly expressed in pancreatic acinar
      cells and that is tightly associated with the lumenal side of the zymogen granule
      membrane. To shed light on the hitherto unknown function of syncollin, we have
      generated syncollin-deficient mice. The mice are viable and show a normal
      pancreatic morphology as well as normal release kinetics in response to
      secretagogue stimulation. Although syncollin is highly enriched in zymogen
      granules, no change was found in the overall protein content and in the levels of
      chymotrypsin, trypsin, and amylase. However, syncollin-deficient mice reacted to
      caerulein hyperstimulation with a more severe pancreatitis. Furthermore, the
      rates of both protein synthesis and intracellular transport of secretory proteins
      were reduced. We conclude that syncollin plays a role in maturation and/or
      concentration of zymogens in zymogen granules.

PMID- 11839819
TI  - Mice lacking the metalloprotease-disintegrin MDC9 (ADAM9) have no evident major
      abnormalities during development or adult life.
AB  - MDC9 (ADAM9/meltrin gamma) is a widely expressed and catalytically active
      metalloprotease-disintegrin protein that has been implicated in the ectodomain
      cleavage of heparin-binding epidermal growth factor-like growth factor (HB-EGF)
      and as an alpha secretase for the amyloid precursor protein. In this study, we
      evaluated the expression of MDC9 during development and generated mice lacking
      MDC9 (mdc9(-/-) mice) to learn more about the function of this protein during
      development and in adults. During mouse development, MDC9 mRNA is ubiquitously
      expressed, with particularly high expression levels in the developing mesenchyme,
      heart and brain. Despite the ubiquitous expression of MDC9, mdc9(-/-) mice appear
      to develop normally, are viable and fertile, and do not have any major
      pathological phenotypes compared to wild-type mice. Constitutive and stimulated
      ectodomain shedding of HB-EGF is comparable in embryonic fibroblasts isolated
      from mdc9(-/-) and wild-type mice, arguing against an essential role of MDC9 in
      HB-EGF shedding in these cells. Furthermore, there were no differences in the
      production of the APP alpha and gamma secretase cleavage product (p3) and of beta
      and gamma-secretase cleavage product (A beta) in cultured hippocampal neurons
      from mdc9(-/-) or wild-type mice, arguing against an essential major role of MDC9
      as an alpha-secretase in mice. Further studies, including functional challenges
      and an evaluation of potential compensation by, or redundancy with, other members
      of the ADAM family or perhaps even with other molecules will be necessary to
      uncover physiologically relevant functions for MDC9 in mice.

PMID- 11839821
TI  - The carboxyl-terminal domain of the protein kinase fused can function as a
      dominant inhibitor of hedgehog signaling.
AB  - The secreted protein hedgehog (Hh) plays a critical role in the developmental
      patterning of multiple tissues. In Drosophila melanogaster, a cytosolic
      multiprotein signaling complex appears necessary for Hh signaling. Genes that
      encode components of this Hh signaling complex (HSC) were originally identified
      and characterized based on their genetic interactions with hh, as well as with
      each other. It is only in recent years that the mechanistic functions of these
      components have begun to be unraveled. Here, we have investigated the
      relationship between two components of the HSC, the serine/threonine protein
      kinase Fused (Fu) and the kinesin-related protein Costal2 (Cos2). We have
      reconstituted a Fu/Cos2 complex in vitro and shown that Fu is able to directly
      associate with Cos2, forming a complex whose molecular size is similar to a
      previously described complex found in Drosophila cell extracts. We have also
      determined that the carboxyl-terminal domain of Fu is necessary and sufficient
      for the direct binding of Fu to Cos2. To validate the physiological relevance of
      this interaction, we overexpressed the carboxyl-terminal domain of Fu in wild
      type flies. These flies exhibit a phenotype similar to that seen in fu mutants
      and consistent with an hh loss-of-function phenotype. We conclude that the
      carboxyl-terminal domain of Fu can function in a dominant negative manner, by
      preventing endogenous Fu from binding to Cos2. Thus, we provide the first
      evidence that Hh signaling can be compromised by targeting the HSC for
      disruption.

PMID- 11839822
TI  - RNA sequence and base pairing effects on insertion editing in Trypanosoma brucei.
AB  - RNA editing inserts and deletes uridylates (U's) in kinetoplastid mitochondrial
      pre-mRNAs by a series of enzymatic steps. Small guide RNAs (gRNAs) specify the
      edited sequence. Editing, though sometimes extensive, is precise. The effects of
      mutating pre-mRNA and gRNA sequences in, around, and upstream of the editing site
      on the specificity and efficiency of in vitro insertion editing were examined.
      U's could be added opposite guiding pyrimidines, but guiding purines,
      particularly A's, were required for efficient ligation. A base pair between mRNA
      and gRNA immediately upstream of the editing site was not required for insertion
      editing, although it greatly enhanced its efficiency and accuracy. In addition, a
      gRNA/mRNA duplex upstream of the editing site enhanced insertion editing when it
      was close to the editing site, but prevented cleavage, and hence editing, when
      immediately adjacent to the editing site. Thus, several aspects of mRNA-gRNA
      interaction, as well as gRNA base pairing with added U's, optimize editing
      efficiency, although they are not required for insertion editing.

PMID- 11839823
TI  - Formation of a carboxy-terminal domain phosphatase (Fcp1)/TFIIF/RNA polymerase II
      (pol II) complex in Schizosaccharomyces pombe involves direct interaction between
      Fcp1 and the Rpb4 subunit of pol II.
AB  - In transcriptional regulation, RNA polymerase II (pol II) interacts and forms
      complexes with a number of protein factors. To isolate and identify the pol II
      associated proteins, we constructed a Schizosaccharomyces pombe strain carrying a
      FLAG tag sequence fused to the rpb3 gene encoding the pol II subunit Rpb3. By
      immunoaffinity purification with anti-FLAG antibody-resin, a pol II complex
      containing the Rpb1 subunit with a nonphosphorylated carboxyl-terminal domain
      (CTD) was isolated. In addition to the pol II subunits, the complex was found to
      contain three subunits of a transcription factor TFIIF (TFIIF alpha, TFIIF beta,
      and Tfg3) and TFIIF-interacting CTD-phosphatase Fcp1. The same type of pol II
      complex could also be purified from an Fcp1-tagged strain. The isolated Fcp1
      showed CTD-phosphatase activity in vitro. The fcp1 gene is essential for cell
      viability. Fcp1 and pol II interacted directly in vitro. Furthermore, by chemical
      cross-linking, glutathione S-transferase pulldown, and affinity chromatography,
      the Fcp1-interacting subunit of pol II was identified as Rpb4, which plays
      regulatory roles in transcription. We also constructed an S. pombe thiamine
      dependent rpb4 shut-off system. On repression of rpb4 expression, the cell
      produced more of the nonphosphorylated form of Rpb1, but the pol II complex
      isolated with the anti-FLAG antibody contained less Fcp1 and more of the
      phosphorylated form of Rpb1 with a concomitant reduction in Rpb4. This result
      indicates the importance of Fcp1-Rpb4 interaction for formation of the
      Fcp1/TFIIF/pol II complex in vivo.

PMID- 11839825
TI  - AZF1 is a glucose-dependent positive regulator of CLN3 transcription in
      Saccharomyces cerevisiae.
AB  - Transcription of the CLN3 G(1) cyclin in Saccharomyces cerevisiae is positively
      regulated by glucose in a process that involves a set of DNA elements with the
      sequence AAGAAAAA (A(2)GA(5)). To identify proteins that interact with these
      elements, we used a 1-hybrid approach, which yielded a nuclear zinc finger
      protein previously identified as Azf1. Gel shift and chromatin
      immunoprecipitation experiments show that Azf1 binds to the A(2)GA(5) CLN3
      regulatory sequences in vitro and in vivo, thus identifying a transcriptional
      regulatory protein for CLN3 and a DNA sequence target for Azf1. We show that
      glucose-induced expression of a reporter gene driven by the A(2)GA(5) CLN3
      regulatory sequences is dependent upon the presence of AZF1. Furthermore,
      deletion of AZF1 markedly reduces the transcriptional induction of CLN3 by
      glucose. In addition, Azf1 can induce reporter expression in a glucose-specific
      manner when artificially tethered to a promoter via the DNA-binding domain from
      Gal4. We conclude that AZF1 is a glucose-dependent transcription factor that
      interacts with the CLN3 A(2)GA(5) repeats to play a positive role in the
      regulation of CLN3 mRNA expression by glucose.

PMID- 11839827
TI  - Questions remaining about the minimally conscious state.

PMID- 11839828
TI  - A better way to find tumor in the CSF?

PMID- 11839829
TI  - Emerging views of dopamine in modulating sleep/wake state from an unlikely
      source: PD.

PMID- 11839824
TI  - Cellular N-Ras promotes cell survival by downregulation of Jun N-terminal protein
      kinase and p38.
AB  - Cellular N-Ras provides a steady-state antiapoptotic signal, at least partially
      through the regulation of phosphorylated Akt and Bad levels. Fibroblasts lacking
      c-N-Ras expression are highly sensitive to the induction of apoptosis by a
      variety of agents. Reduction of pBad and pAkt levels using a phosphatidylinositol
      3-kinase inhibitor was not sufficient to sensitize the control cell population to
      the high level of apoptosis observed in the N-Ras knockout cell lines, suggesting
      that c-N-Ras provides at least one other antiapoptotic signal. Stimulation of the
      control cells with apoptotic agents results in a transient increase in Jun N
      terminal protein kinase (JNK)/p38 activity that decreased to baseline levels
      during the time course of the experiments. In all cases, however, sustained
      JNK/p38 activity was observed in cells lacking c-N-Ras expression. This
      correlated with sustained levels of phosphorylated MKK4 and MKK3/6, upstream
      activators of JNK and p38, respectively. Mimicking the sustained activation of
      JNK in the control cells did result in increasing their sensitivity to apoptotic
      agents, suggesting that prolonged JNK activity is a proapoptotic event. We also
      examined the potential downstream c-N-Ras targets that might be involved in
      regulating the duration of the JNK/p38 signal. Only the RalGDS 37G-N-Ras protein
      protected the N-Ras knockout cells from apoptosis and restored transient rather
      than sustained JNK activation. These data suggest that cellular N-Ras provides an
      antiapoptotic signal through at least two distinct mechanisms, one which
      regulates steady-state pBad and pAkt levels and one which regulates the duration
      of JNK/p38 activity following an apoptotic challenge.

PMID- 11839830
TI  - Reporting clinical trials: full access to all the data.

PMID- 11839831
TI  - The minimally conscious state: definition and diagnostic criteria.
AB  - OBJECTIVE: To establish consensus recommendations among health care specialties
      for defining and establishing diagnostic criteria for the minimally conscious
      state (MCS). BACKGROUND: There is a subgroup of patients with severe alteration
      in consciousness who do not meet diagnostic criteria for coma or the vegetative
      state (VS). These patients demonstrate inconsistent but discernible evidence of
      consciousness. It is important to distinguish patients in MCS from those in coma
      and VS because preliminary findings suggest that there are meaningful differences
      in outcome. METHODS: An evidence-based literature review of disorders of
      consciousness was completed to define MCS, develop diagnostic criteria for entry
      into MCS, and identify markers for emergence to higher levels of cognitive
      function. RESULTS: There were insufficient data to establish evidence-based
      guidelines for diagnosis, prognosis, and management of MCS. Therefore, a
      consensus-based case definition with behaviorally referenced diagnostic criteria
      was formulated to facilitate future empirical investigation. CONCLUSIONS: MCS is
      characterized by inconsistent but clearly discernible behavioral evidence of
      consciousness and can be distinguished from coma and VS by documenting the
      presence of specific behavioral features not found in either of these conditions.
      Patients may evolve to MCS from coma or VS after acute brain injury. MCS may also
      result from degenerative or congenital nervous system disorders. This condition
      is often transient but may also exist as a permanent outcome. Defining MCS should
      promote further research on its epidemiology, neuropathology, natural history,
      and management.

PMID- 11839832
TI  - Cluster headache: a prospective clinical study with diagnostic implications.

PMID- 11839833
TI  - Insomnia associated with thalamic involvement in E200K Creutzfeldt-Jakob disease.
AB  - BACKGROUND: Insomnia with predominant thalamic involvement and minor cortical and
      cerebellar pathologic changes is not characteristic of familial Creutzfeldt-Jakob
      disease (CJD) but is a hallmark of fatal familial insomnia. OBJECTIVE: To report
      a 53-year-old woman with intractable insomnia as her initial symptom of disease.
      METHODS: The authors characterized clinical, pathologic, and molecular features
      of the disease using EEG, polysomnography, neurohistology, Western blotting,
      protein sequencing, and prion protein (PrP) gene (PRNP) analysis. RESULTS: The
      patient developed dysgraphia, dysarthria, bulimia, myoclonus, memory loss, visual
      hallucinations, and opisthotonos, as well as pyramidal, extrapyramidal, and
      cerebellar signs. Polysomnographic studies showed an absence of stages 3 and 4,
      and REM. She died 8 months after onset. On neuropathologic examination, there was
      major thalamic involvement characterized by neuronal loss, spongiform changes,
      and prominent gliosis. The inferior olivary nuclei exhibited chromatolysis,
      neuronal loss, and gliosis. Spongiform changes were mild in the neocortex and not
      evident in the cerebellum. PrP immunopositivity was present in these areas as
      well as in the thalamus. PRNP analysis showed the haplotype E200K-129M. Western
      blot analysis showed the presence of proteinase K (PK)-resistant PrP (PrP(sc))
      with the nonglycosylated isoform of approximately 21 kd, corresponding in size to
      that of type 1 PrP(sc). N-terminal protein sequencing demonstrated PK cleavage
      sites at glycine (G) 82 and G78, as previously reported in CJD with the E200K-129
      M haplotype. CONCLUSIONS: Insomnia may be a prominent early symptom in cases of
      CJD linked to the E200K-129M haplotype in which the thalamus is severely
      affected.

PMID- 11839835
TI  - Ictal hyperperfusion patterns according to the progression of temporal lobe
      seizures.
AB  - OBJECTIVE: To investigate ictal hyperperfusion patterns during semiologic
      progression of seizures, the authors performed SPECT subtraction in 50 patients
      with temporal lobe epilepsy (TLE). METHODS: The patients were categorized into
      five groups according to semiologic progression during ictal SPECT (Group 1 had
      aura only; Group 2 had motionless staring with or without aura; Group 3 had
      motionless staring and then automatism with or without aura; Group 4 had
      motionless staring and then dystonic posturing with or without aura and
      automatism; and Group 5 had motionless staring, automatism, then head version and
      generalized seizures with or without aura and dystonic posturing). RESULTS: In
      Group 1, three patients showed ipsilateral temporal hyperperfusion and two had
      bilateral temporal hyperperfusion with ipsilateral predominance. In Group 2,
      three patients (42.9%) showed bilateral temporal hyperperfusion with unilateral
      predominance and four patients (57.1%) revealed insular hyperperfusion of
      epileptic side. In Group 3, 15 patients (88.2%) showed bilateral temporal
      hyperperfusion with unilateral predominance and 12 patients (70.6%) revealed
      insular hyperperfusion. In Group 4, 11 patients (84.6%) showed basal ganglia
      hyperperfusion on the opposite hemisphere to the side of the dystonic posturing.
      In Group 5, there were multiple hyperperfusion areas in the frontal, temporal,
      and basal ganglia regions. However, the injection times of radiotracer in five
      groups were relatively short and similar. CONCLUSIONS: The semiologic progression
      in TLE seizures were related to the propagation of hyperperfusion from
      ipsilateral temporal lobe to contralateral temporal lobe, insula, basal ganglia,
      and frontal lobe. Not only the radiotracer injection time but also semiologic
      progression after the injection was important to determine hyperperfusion pattern
      of ictal SPECT.

PMID- 11839834
TI  - Modulation of cerebral GABA by topiramate, lamotrigine, and gabapentin in healthy
      adults.
AB  - BACKGROUND: Anticonvulsant drugs have multiple mechanisms of action. Recent in
      vivo MRS studies suggest that cerebral gamma-aminobutyric acid (GABA) increases
      occur with the administration of certain anticonvulsants in humans. OBJECTIVE: To
      investigate the effect of topiramate, gabapentin, and lamotrigine on cerebral
      GABA concentrations in healthy volunteers and correlate the GABA concentrations
      with serum drug levels. METHODS: Seventeen healthy adults were randomly assigned
      to receive topiramate, gabapentin, and lamotrigine and underwent GABA
      measurements using a 4.1-T magnet from a 13.5-mL volume over the occipital
      region. GABA concentrations and serum levels were measured at 3 and 6 hours
      following administration of an acute single dose of one of the drugs. Thereafter,
      drugs were titrated over 4 weeks to target doses, with GABA measurements
      performed at 2 and 4 weeks. RESULTS: Cerebral GABA concentrations rose 70% in the
      acute phase compared with baseline for topiramate. GABA rose 48% at 6 hours with
      gabapentin but not with lamotrigine. With long-term dosing and once target doses
      were achieved at 4 weeks, significant elevations in GABA were observed compared
      with baseline for all three drugs (topiramate 46%, gabapentin 25%, lamotrigine
      25%). CONCLUSION: This study demonstrates that single doses of topiramate and
      gabapentin increase cerebral GABA concentrations acutely (hours) in healthy
      individuals, but all drugs at clinically utilized doses increase cerebral GABA at
      4 weeks. These results suggest that the mechanisms of action of anticonvulsant
      drugs are more complex and are likely to be multiple in nature.

PMID- 11839836
TI  - Activation in primary and secondary motor areas in patients with CNS neoplasms
      and weakness.
AB  - OBJECTIVE: To demonstrate whether cortical activation within different cortical
      motor regions in neurosurgical patients varies with the degree of paresis induced
      by mass lesions near the central region. METHODS: A total of 110 patients with
      brain tumors infiltrating the central region and with varying degrees of paresis
      were investigated employing fMRI during the performance of hand motor tasks. The
      percent signal change between rest and activation was calculated for four
      cortical regions: primary motor cortex (M1), supplementary motor area, premotor
      area, and superior parietal lobule. RESULTS: Significant decreases in activation
      with increasing degrees of paresis were found in M1, whereas significant
      increases in activation were noted in secondary motor areas that were not
      affected by the tumor. CONCLUSIONS: The signal loss in areas adjacent to tumor
      tissue may relate either to tumor-induced changes in cerebral hemodynamics or to
      a direct loss of cortical neurons resulting in a lesser degree of hemodynamic
      changes after motor activation. The increase in activation within secondary motor
      areas with increasing degrees of paresis supports the growing evidence of a
      practice- and lesion-dependent reorganization of the cortical motor system and
      the ability of the brain to modulate its excitatory output according to external
      demands.

PMID- 11839837
TI  - CSF evaluation in primary CNS lymphoma patients by PCR of the CDR III IgH genes.
AB  - BACKGROUND: Cytologic evaluation of CSF does not consistently detect malignant
      cells in patients with primary CNS lymphoma (PCNSL). The potentially more
      sensitive molecular assessment of monoclonality has not been shown in CSF
      samples. METHODS: The authors studied nested PCR of the complementary determining
      region III (CDR III) on 76 CSF specimens of patients with PCNSL. Patients with
      systemic disseminated B-cell non-Hodgkin's lymphoma (n = 17) and 17 patients with
      no history of lymphoma were compared. PCR products were evaluated by automated
      fluorescent fragment analysis (ALF). RESULTS: In 68 patients with PCNSL, the
      authors analyzed the first obtained CSF sample. Nevertheless, 60 patients were
      taking corticosteroids. In 16 PCNSL samples, amplifiable DNA was not yielded.
      Taking into account that at least two independent assays have to be performed,
      CDR III PCR consistently revealed monoclonal products in eight PCNSL and
      polyclonal results in 52 PCNSL specimens. CDR III PCR detected no monoclonal PCR
      products in patients without history of lymphoma. In 10 patients with PCNSL, the
      PCR result and the CSF cytology were discordant. Concerning therapeutic impact,
      leptomeningeal tumor spread did not predict tumor response in this group of
      patients with PCNSL. CONCLUSIONS: This study performed CDR III PCR as a routine
      diagnostic technique applicable even on CSF samples with low cell counts. These
      data present low incidence of leptomeningeal involvement in this subset of
      pretreated PCNSL patients. Because the CSF evaluation did not predict outcome in
      our patients, further analysis in patients with PCNSL should focus on CSF samples
      that are obtained very early after diagnosis.

PMID- 11839838
TI  - Subthalamic DBS replaces levodopa in Parkinson's disease: two-year follow-up.
AB  - BACKGROUND: Subthalamic nucleus (STN) deep brain stimulation (DBS) of patients
      with PD allows reduction of antiparkinsonian medication but has only a mild
      direct effect on dyskinesia. Since antiparkinsonian medication has short- and
      long-term effects that may prevent an estimate of the maximal possible impact of
      STN DBS, such medication was used at the lowest possible dosage after DBS
      implantation. OBJECTIVE: To study the maximal and long-term effects of STN DBS
      using the lowest dose of medication. METHODS: Twenty consecutive patients with PD
      with motor fluctuations and dyskinesia underwent bilateral implantation under
      stereotactic guidance, microrecording, and clinical control. All medications were
      stopped before implantation and reintroduced, at the lowest dosage needed, only
      if the postoperative motor score did not reach the baseline level. Unified PD
      Rating Scale (UPDRS) motor (subscale III) scores were measured at baseline and
      after 3, 6, 12, and 24 months. RESULTS: After 21 plus minus 8 months, the UPDRS
      III "off-medication" score was decreased by 45% and was similar to the
      preoperative UPDRS III "on" score. Overall, medication was reduced by 79%, being
      completely withdrawn in 10 patients. Fluctuations and dyskinesia showed an
      overall reduction of >90%, disappearing completely in patients without
      medication. These improvements were maintained for 2 years. CONCLUSIONS: These
      results show that STN DBS could replace levodopa and allowed all antiparkinsonian
      medication to be discontinued in 50% of patients with PD. Fluctuations and
      dyskinesia disappeared completely in these patients but persisted in those still
      on medication. These improvements were maintained for 2 years.

PMID- 11839839
TI  - Thalamic stimulation reduces essential tremor but not the delayed antagonist
      muscle timing.
AB  - BACKGROUND: Electrical stimulation of the thalamus dramatically reduces essential
      tremor (ET). It has been hypothesized that the cerebellum and inferior olive are
      involved in the generation of ET, and thalamic stimulation is presumed to dampen
      ET through interactions with cerebellar output to the thalamus. Evidence suggests
      that abnormal timing of agonist and antagonist muscle responses contribute to
      cerebellar tremor (CbT); however, this relationship has not been investigated for
      ET. The mechanisms of the tremor and improvement are unknown. OBJECTIVE: To
      measure the effect of ventral intermediate thalamic stimulation in controlling
      the ET response to sudden stretch of an agonist muscle and to determine whether,
      in ET, the timing relationships between the initial agonist and antagonist
      electromyography (EMG) responses show abnormalities similar to those seen in CbT.
      METHODS: The authors studied ET subjects (with implanted thalamic stimulators
      turned off and on) and normal controls as they responded to mechanical torque
      pulses given at the wrist joint. The wrist joint angle, wrist agonist, and
      antagonist EMG were recorded. RESULTS: Like CbT, patients with ET showed delayed
      onsets of antagonist EMG and excessive rebound. Thalamic stimulation reduced the
      tremor but did not alter the antagonist delay or the rebound. CONCLUSIONS: In ET,
      antagonist muscle responses to a torque pulse are similar to that in CbT.
      However, benefit from thalamic stimulation did not alter these EMG responses;
      therefore, suppression of tremor must be caused by mechanisms other than the re
      establishment of normal agonist-antagonist timing.

PMID- 11839840
TI  - Spastic paraplegia, ataxia, mental retardation (SPAR): a novel genetic disorder.
AB  - OBJECTIVE: To describe a kindred with a dominantly inherited neurologic disorder
      manifested either as uncomplicated spastic paraplegia or ataxia, spastic
      paraplegia, and mental retardation. METHODS: Neurologic examinations and
      molecular genetic analysis (exclusion of known SCA and HSP genes and loci; and
      trinucleotide repeat expansion detection [RED]) were performed in six affected
      and four unaffected subjects in this family. MRI, electromyography (EMG), and
      nerve conduction studies were performed in three affected subjects. RESULTS: The
      phenotype of this dominantly inherited syndrome varied in succeeding generations.
      Pure spastic paraplegia was present in the earliest generation; subsequent
      generations had ataxia and mental retardation. MRI showed marked atrophy of the
      spinal cord in all patients and cerebellar atrophy in those with ataxia.
      Laboratory analysis showed that the disorder was not caused by mutations in genes
      that cause SCA-1, SCA-2, SCA-3, SCA-6, SCA-7, SCA-8, and SCA-12; not linked to
      other known loci for autosomal dominant ataxia (SCA-4, SCA-5, SCA-10, SCA-11, SCA
      13, SCA-14, and SCA-16); and not linked to known loci for autosomal dominant
      hereditary spastic paraplegia (HSP) (SPG-3, SPG-4, SPG-6, SPG-8, SPG-9, SPG-10,
      SPG-12, and SPG-13) or autosomal recessive HSP SPG-7. Analysis of
      intergenerational differences in age at onset of symptoms suggests genetic
      anticipation. Using RED, the authors did not detect expanded CAG, CCT, TGG, or
      CGT repeats that segregate with the disease. CONCLUSIONS: The authors describe an
      unusual, dominantly inherited neurologic disorder in which the phenotype (pure
      spastic paraplegia or spastic ataxia with variable mental retardation) differed
      in subsequent generations. The molecular explanation for apparent genetic
      anticipation does not appear to involve trinucleotide repeat expansion.

PMID- 11839841
TI  - MRI metrics as surrogate markers for clinical relapse rate in relapsing-remitting
      MS patients.
AB  - OBJECTIVE: To formally validate metrics derived from conventional MRI as
      surrogate endpoints for relapse rate in MS. BACKGROUND: Although metrics derived
      from MRI are used widely in clinical trials of MS, a formal statistical
      validation of MRI metrics as surrogate endpoints for clinical outcome in MS is
      lacking. METHODS: A validation procedure was applied to clinical and MRI data
      collected in the context of a randomized, double-blind, placebo-controlled trial
      of glatiramer acetate in patients with relapsing-remitting MS. The four Prentice
      operational criteria were applied to assess surrogacy for the number of new
      enhancing lesions, the percentage change of T2 lesion volume, and a composite MRI
      score based on these two metrics. RESULTS: The results of this analysis show that
      all three MRI measures considered by the authors had a behavior compatible with
      the Prentice criteria for valid surrogates. The composite MRI score correlated
      with relapses and accounted for much of the treatment effect on relapse rate.
      CONCLUSIONS: This preliminary study suggests that conventional MRI metrics might
      serve as valid surrogate endpoints in MS trials with glatiramer acetate or
      treatments thought to have a similar mode of action.

PMID- 11839842
TI  - Migraine and autonomic nervous system function: a population-based, case-control
      study.
AB  - OBJECTIVE: This study determines if measures of the function of the autonomic
      nervous system (ANS) differ in a population study of 80 migraine cases vs 85
      controls matched for age, race, and sex. BACKGROUND: The authors sought to
      confirm clinic-based studies suggesting that migraine is associated with abnormal
      ANS function. METHODS: Resting systolic and diastolic blood pressure, Valsalva
      maneuver, heart rate variability (pulse rate [RR] variation) during deep
      breathing, and cardiovascular reactivity were measured during headache-free
      intervals. Migraineurs were subdivided into those with (n = 28) and without (n =
      52) disabling headaches. RESULTS: Resting diastolic, but not systolic, blood
      pressure was elevated in disabled (73.2 mm) compared with nondisabled cases (71.6
      mm; p < 0.10) and controls (69.8 mm; p < 0.096). RR variation also was
      significantly different among the three groups. Disabled migraine cases (1.19)
      had significantly lower RR variation compared with nondisabled migraine cases
      (1.26; p < 0.001) and controls (1.26; p < 0.001). The Valsalva ratio and mean
      circular resultant were lower in disabled cases compared with other migraine
      cases and with controls, but the differences were not statistically significant.
      No differences were found between the three groups when comparing blood pressure
      response to a psychological stressor. CONCLUSIONS: Migraineurs with disabling
      attacks may be prone to ANS hypofunction. These findings may suggest that ANS
      dysfunction either may be a risk factor for migraine headaches or be a
      consequence of frequent disabling attacks. Moreover, ANS dysfunction and migraine
      may share a common neural substrate.

PMID- 11839843
TI  - Minicolumnar pathology in autism.
AB  - OBJECTIVE: To determine whether differences exist in the configuration of
      minicolumns between the brains of autistic and control patients. BACKGROUND:
      Autism is a severe and pervasive developmental disturbance of childhood
      characterized by disturbances in both social interactions and communication, as
      well as stereotyped patterns of interests, activities, and behaviors. Postmortem
      neuropathologic studies remain inconclusive. METHODS: The authors used a
      computerized imaging program to measure details of cell column morphologic
      features in area 9 of the prefrontal cortex and areas 21 and posterior 22 (Tpt)
      within the temporal lobe of nine brains of autistic patients and controls.
      RESULTS: The authors found significant differences between brains of autistic
      patients and controls in the number of minicolumns, in the horizontal spacing
      that separates cell columns, and in their internal structure, that is, relative
      dispersion of cells. Specifically, cell columns in brains of autistic patients
      were more numerous, smaller, and less compact in their cellular configuration
      with reduced neuropil space in the periphery. CONCLUSIONS: In autism, there are
      minicolumnar abnormalities in the frontal and temporal lobes of the brain.

PMID- 11839844
TI  - A videotaped CIBIC for dementia patients: validity and reliability in a simulated
      clinical trial.
AB  - BACKGROUND: The global impression of a clinician is an Food and Drug
      Administration--mandated primary outcome measure for clinical trials in dementia.
      Reliability and validity of these measures are not well established. METHODS: A
      videotaped version of the Clinician's Interview Based Impression of Change
      (CIBIC) was evaluated. Raters were informed that the videotaped interviews were
      taken at baseline and 6 to 12 months later, when in fact half of the interviews
      were shown in reverse order. Ratings on "true order" interviews were compared
      with ratings on "reverse order" interviews. In addition, ratings by neurologists
      experienced in dementia were compared with those of less experienced raters.
      RESULTS: Inter-rater reliability of the neurologists was poor when measured by
      absolute agreement on a 7-point scale (kappa = 0.18). With a less stringent 3
      point scale (better, worse, or unchanged), inter-rater reliability was
      significantly better for the true order videos (kappa = 0.51) than for the
      reversed order videos (kappa = 0.12). Validity also was reduced in the reverse
      order group: neurologists rated 90% of subjects correctly in the "true order"
      group and 63% correctly in the "reversed order" group. The inter-rater
      reliability of the neurologists was greater than the less experienced raters, but
      the validity of the neurologists' ratings was only marginally better.
      CONCLUSIONS: The reliability and validity of the videotape CIBIC are reasonable
      when patients follow the expected course of gradual decline, but are poor when
      patients appear to improve. These findings suggest that global assessments should
      be modified as outcome measures in clinical trials with patients with dementia.

PMID- 11839845
TI  - Three lipoprotein receptors and cholesterol in inclusion-body myositis muscle.
AB  - BACKGROUND: An important aspect of inclusion-body myositis (IBM) vacuolated
      muscle fibers (VMF) is abnormal accumulation of amyloid-beta precursor protein
      (AbetaPP) epitopes and its product, amyloid-beta (Abeta), and of phosphorylated
      tau (p-tau) in the form of paired helical filaments. Lipoprotein receptors and
      cholesterol are known to play an important role in AbetaPP processing, Abeta
      production, and tau phosphorylation. METHODS: In 10 IBM and 22 control muscle
      biopsies the authors immunolocalized low-density lipoprotein receptor (LDLR),
      very low-density lipoprotein receptor (VLDLR), and low-density lipoprotein
      receptor-related protein (LRP), and colocalized them with Abeta, p-tau, APOE, and
      free cholesterol. RESULTS: In each biopsy, virtually all IBM VMF had strong LDLR
      immunoreactive inclusions, which colocalized with Abeta, APOE, p-tau, and free
      cholesterol. VLDLR was increased mainly diffusely, but in approximately 50% of
      the VMF it was also accumulated in the form of inclusions colocalizing with
      Abeta, APOE, and free cholesterol, but not with p-tau. LRP inclusions were
      present in a few VMF. In all myopathies, a subset of regenerating and necrotizing
      muscle fibers had prominent diffuse accumulation of both LDLR and free
      cholesterol. At normal neuromuscular junctions (NMJ) postsynaptically, LDLR and
      VLDLR, but not LRP, were immunoreactive. CONCLUSIONS: 1) Abnormal accumulation of
      LDLR, VLDLR, LRP, and cholesterol within IBM vacuolated muscle fibers suggests
      novel roles for them in the IBM pathogenesis. 2) Expression of LDLR and VLDLR at
      normal NMJ suggests physiologic roles for them in transsynaptic signaling
      pathways, increased internalization of lipoproteins there, or both. 3) Increased
      LDLR and free cholesterol in some regenerating and necrotizing muscle fibers
      suggest a role for them in human muscle fiber growth and repair and necrotic
      death.

PMID- 11839847
TI  - Release of soluble ICAM-5, a neuronal adhesion molecule, in acute encephalitis.
AB  - BACKGROUND: Intercellular adhesion molecule (ICAM)-5 (telencephalin) is an
      adhesion molecule in telencephalic neurons of the mammalian brain that binds to
      the leukocyte integrin CD11a/CD18. The authors observed that human cerebral
      neurons also expressed ICAM-5 and that ICAM-5--mediated neuron--leukocyte binding
      in cultured hippocampal neurons. This led the authors to examine ICAM-5
      expression during clinical CNS inflammation. METHODS: The authors found, by
      immunoblotting, a 115-kDa soluble form of ICAM-5 (sICAM-5) cleaved from the
      membrane-bound (130 kDa) ICAM-5, and established an ELISA assay to measure it.
      CSF samples of patients with acute encephalitis and MS were studied. RESULTS:
      sICAM-5 was increased in encephalitis (320 plus minus 107 ng/mL; n = 25), as
      compared with patients with MS (128 plus minus 10 ng/mL; n = 16) and control
      subjects without CNS disease (137 plus minus 6 ng/mL; n = 42) (p < 0.001). The
      concentration of sICAM-5 correlated with the performance in the immediate recall
      task (p = 0.013) and with the leukocyte count in the CSF (p = 0.02), especially
      in cases caused by herpes simplex virus (HSV) (r = 0.94; p = 0.002). CONCLUSIONS:
      sICAM-5 is cleaved from CNS into CSF during acute encephalitis, and it may
      mediate leukocyte--neuron interactions. sICAM-5 release from cerebral neurons may
      actively regulate immune responses and leukocyte adhesion during microbial
      neuroinvasion in humans during encephalitis.

PMID- 11839848
TI  - J.L. Corning and vagal nerve stimulation for seizures in the 1880s.
AB  - Beginning in the late 18th century, facial flushing and bounding carotid artery
      pulses during seizures were seen as evidence that seizures resulted from "venous
      hyperaemia" of the CNS. Consequently, physicians used digital compression of the
      carotid artery, and later carotid ligation, to abort seizures. In the early
      1880s, New York neurologist James Leonard Corning (1855--1923) developed several
      instruments for carotid artery compression in the treatment of seizures. These
      devices included a two-pronged, fork-like instrument (the "carotid fork") for
      temporary compression as an abortive treatment and an adjustable belt-like
      instrument to encircle the neck (the "carotid truss") for chronic compression as
      a prophylactic treatment. Corning's uncontrolled observations suggested that the
      abortive treatment decreased the duration of seizures and that the prophylactic
      treatment decreased the frequency of seizures. Corning later combined
      instrumented carotid artery compression with other devices to decrease cerebral
      blood flow, including transcutaneous electrical vagal nerve and cervical
      sympathetic stimulation. Observed side effects of treatment included bradycardia,
      dizziness, and syncope. Corning's use of instrumented carotid compression and his
      precocious application of transcutaneous electrical vagal nerve stimulation were
      not widely adopted by neurologists, and these techniques and devices ultimately
      were abandoned in the late 19th century.

PMID- 11839849
TI  - Cavernous malformation of the facial colliculus.

PMID- 11839850
TI  - Effect of ropinirole on sleep onset: a randomized, placebo-controlled study in
      healthy volunteers.
AB  - Somnolence and "sleep attacks" have been reported as an adverse effect of several
      antiparkinsonian drugs. The authors document, in a placebo-controlled,
      randomized, double-blind, crossover study performed in 20 healthy volunteers,
      using the Multiple System Latency Test (MSLT) as primary outcome, that ropinirole
      reduces time to sleep onset in humans. Ropinirole therapy was not associated with
      daytime episodes of rapid eyes movement (REM) sleep.

PMID- 11839851
TI  - Polysomnographic characterization of pergolide-induced sleep attacks in
      idiopathic PD.
AB  - Both dopamine agonists and levodopa may induce episodes termed "sleep attacks" in
      patients with PD. These episodes are well detailed behaviorally, but little is
      known about their neurophysiologic characterization. The authors performed a 24
      hour polysomnography (PSG) in a PD patient taking pergolide in combination with
      levodopa, in which four of these diurnal sleep episodes occurred. PSG findings
      were followed up after pergolide withdrawal. Sleep episodes shared with
      narcolepsy both behavioral and EEG findings. However, pergolide partly restored a
      more physiologic sleep architecture, which was disrupted during therapy with
      levodopa alone.

PMID- 11839853
TI  - Further supporting evidence of beneficial subthalamic stimulation in Parkinson's
      patients.
AB  - Twenty-two patients with Parkinson's disease were treated by implanting
      electrodes in the subthalamic nucleus. The follow-up evaluation was conducted at
      one (22 patients) and two years (9 patients). Significant improvement in the
      Unified PD Rating Scale scores was found. Tremor diminished 100% in the on
      drug/on stimulation and 70% off drug/on stimulation state. Rigidity decreased by
      68% in the on drug/on stimulation and by 52% in off drug/on stimulation state.
      Subthalamic stimulation is reliable.

PMID- 11839852
TI  - Evaluation of somnolence in Parkinson's disease: comparison with age- and sex
      matched controls.
AB  - The authors found a significantly higher prevalence of daytime somnolence in 201
      patients with PD compared with 214 age- and sex-matched healthy control subjects
      (Epworth Sleepiness Scale score 5.6 vs 4.6). The prevalence of "sleep attacks"
      (SA) was about seven times higher in patients with PD than in control subjects
      (13.9% vs 1.9%; p < 0.0005). Multivariate analysis demonstrated that a higher
      dose of levodopa and longer duration of disease significantly predicted for SA in
      patients with PD. Epworth Sleepiness Scale scores of > or =10 had 71.4%
      sensitivity and 88.4% specificity for SA.

PMID- 11839854
TI  - Multiple sclerosis-associated retrovirus (MSRV) in Sardinian MS patients.
AB  - Blood and CSF of Sardinian patients with MS and neurologic control subjects were
      tested for MS-associated retrovirus (MSRV). CSF detection in MS was 50% at
      clinical onset, increasing with temporal disease progression, and 40% in control
      subjects. In blood, MSRV was detected in all MS patients, in most patients with
      inflammatory neurologic diseases, and rarely in healthy blood donors. MSRV may
      represent a marker of neurologic diseases of inflammatory origin.

PMID- 11839855
TI  - Ischemic brain tissue salvaged from infarction by the GP IIb/IIIa platelet
      antagonist tirofiban.
AB  - In an open pilot study, the authors tested whether the nonpeptide glycoprotein
      (GP) IIb/IIIa antagonist tirofiban, a highly effective and selective blocker of
      platelet aggregation, prevents the transition of ischemic brain tissue into the
      infarct proper as defined by MRI (perfusion-weighted/T2-weighted) in patients
      with acute ischemic stroke. The infarct volume (T2 lesion after 1 week) was
      smaller in treated patients (n = 10) compared with matched control subjects (n =
      10; p = 0.029) with similar initial perfusion deficit (TTP-maps). The authors
      conclude that GP IIb/IIIa antagonists have therapeutic potential in acute stroke
      therapy.

PMID- 11839856
TI  - Non-T(H)1 cytokines are augmented systematically early in Guillain-Barre
      syndrome.
AB  - The T(H)1 vs non-T(H)1 cytokine balance in Guillain-Barre syndrome (GBS) is
      unknown. Using enzyme-linked immunospot (ELISPOT) assays, we observed elevated
      numbers of interleukin (IL)-6 and IL-10-secreting blood mononuclear cells (BMNC)
      during the acute phase in untreated patients, and low levels of tumor necrosis
      factor alpha-secreting BMNC in the recovery phase of GBS. Numbers of IL-12p70
      secreting BMNC were not affected over the course of GBS. The non-T(H)1 cytokine
      profile observed early in GBS may explain the self-limited clinical course
      associated with GBS.

PMID- 11839858
TI  - Women with pregnancy-related polymyositis and high serum CK levels in the
      newborn.
AB  - Two previously healthy women developed an inflammatory myopathy before the term
      of their first pregnancy. Skeletal muscle biopsy led to a diagnosis of T cell
      mediated polymyositis. Both babies were healthy, but their serum creatine kinase
      levels remained elevated for a few months after birth. Their mothers did well
      after corticosteroid treatment.

PMID- 11839857
TI  - Axonal damage is a late component of vacuolar myelopathy.
AB  - The role of axonopathy in myelin disorders recently has been examined. To
      investigate axonal pathologic changes in vacuolar myelopathy (VM),
      semiquantitative immunohistochemical stains for inflammation, axonal damage, and
      gliosis were performed on spinal cord sections from patients with AIDS with and
      without VM and from HIV-negative controls. Significant axonal damage was present
      in only moderate to severe VM, despite inflammation at all stages. The authors
      conclude that axonal damage is not present in early disease; it is present in
      moderate to severe vacuolar myelopathy and may contribute to clinical deficits in
      late stages of this disorder.

PMID- 11839859
TI  - Gastrostomy insertion in ALS patients with low vital capacity: respiratory
      support and survival.
AB  - The authors evaluated their uncontrolled, retrospective experience with 33
      patients with ALS with erect or supine forced vital capacity less than 50%
      predicted who underwent attempted percutaneous endoscopic gastrostomy (PEG) tube
      placement using noninvasive positive pressure ventilation and oxygen support and
      conscious sedation anesthesia. Gastrostomy tubes were successfully placed in all
      patients. Mean survival was 211 days with most patients (67%) surviving more than
      180 days. Forced vital capacity at the time of PEG placement did not predict
      survival.

PMID- 11839860
TI  - Forced collectionism after orbitofrontal damage.
AB  - A collector is a person who collects things on purpose, either as a hobby or
      business, or for personal satisfaction, e.g., stamp, coin, or art collector. In
      such instances, the act of collecting things represents voluntary, controlled,
      goal-directed, selective searching. Pathologic patterns of collecting have been
      observed following brain damage, particularly frontal lobe damage, ranging from a
      tendency to grasp (prehension behavior) to an irrepressible need to seize
      surrounding objects and store them (hoarding behavior). These adnormal behaviors
      express an excessive adherence to environmental stimuli but in no way express a
      planned process directed toward specific items. In this article, we describe an
      unusual pattern of pathologic collecting behavior due to frontal lobe damage:
      involuntary irrepressible collecting that is goal-directed and selective. The
      authors report a patient who collected specifically household electrical
      appliances following a bilateral damage of orbito- and polar-prefrontal cortex.
      The patient had involuntary irrepressible collecting that was goal-directed and
      selective. This "forced collectionism" is different from that of the usual
      collectionism encountered in patients with frontal lobe lesions, as the latter is
      in no way a planned process directed toward specific items.

PMID- 11839861
TI  - False lateralization of language cortex on functional MRI after a cluster of
      focal seizures.
AB  - fMRI can define language cortex but its limitations are not yet fully understood.
      This article describes a child in whom fMRI falsely lateralized language cortex
      when performed after a cluster of left temporal lobe seizures. Multiple language
      tasks revealed no activation over the left temporal lobe despite a normal
      neurologic exam at the time of the study. A second fMRI performed 2 weeks later
      activated sites predominantly over the left, which were confirmed by extra
      operative functional language mapping. fMRI may be unhelpful after frequent
      seizures.

PMID- 11839862
TI  - Diagnostic delay in psychogenic nonepileptic seizures.
AB  - Delay to diagnosis was studied in 313 consecutive patients with psychogenic
      nonepileptic seizures (PNES). On average, patients with PNES were diagnosed 7.2
      years after manifestation (SD 9.3 years). Younger age, interictal epileptiform
      potentials in the EEG, and anticonvulsant treatment were associated with longer
      delays. Other patient factors did not explain the great variability of the time
      to diagnosis, suggesting that physician factors contributed to delays.

PMID- 11839863
TI  - Will neurology residents with large student loan debts become academicians?
AB  - Medical education in the United States is expensive, with 4-year tuition at some
      institutions totaling more than 150,000 US dollars. Most US graduates have
      student debt burdens. Using an internet survey, we tested the hypothesis that
      high student debt adversely affects neurology residents' desire to pursue careers
      in academic neurology. The results indicate median year 2000 US graduate
      neurology resident student debt is in the 50,000 to 75,000 US dollars range and
      that this debt burden may deter US graduates from pursuing careers in academic
      neurology.

PMID- 11839864
TI  - Normal hypocretin-1 levels in Parkinson's disease patients with excessive daytime
      sleepiness.

PMID- 11839865
TI  - Speaking while gesturing: the relationship between speech and limb praxis.

PMID- 11839866
TI  - Pituitary apoplexy presenting as postoperative stupor.

PMID- 11839867
TI  - Coital headaches induced by amiodarone.

PMID- 11839868
TI  - Recurrent trismus and stridor in an ALS patient: successful treatment with
      botulinum toxin.

PMID- 11839869
TI  - Symptomatic hyperekplexia in a patient with multiple sclerosis.

PMID- 11839870
TI  - Palatal tremor and myorhythmia in Hashimoto's encephalopathy.

PMID- 11839871
TI  - CNS siderosis after brachial plexus avulsion.

PMID- 11839872
TI  - The minimally conscious state: definition and diagnostic criteria.

PMID- 11839873
TI  - Effect of L-carnitine treatment for valproate-induced hepatotoxicity.

PMID- 11839874
TI  - Basal forebrain malformation with hyperhidrosis and hypothermia: variant of
      Shapiro's syndrome.

PMID- 11839876
TI  - Hand weakness from a precentral gyrus infarct with intermittent hypotension.

PMID- 11839875
TI  - CSF detection of the 14-3-3 protein in unselected patients with dementia.

PMID- 11839877
TI  - Calamities and cardiac arrhythmias: the medical and scientific impact of
      epidemics of suffering.

PMID- 11839878
TI  - Cooled-tip ablation results in increased radiofrequency power delivery and lesion
      size in the canine heart: importance of catheter-tip temperature monitoring for
      prevention of popping and impedance rise.
AB  - Since myocardial lesion size during radio-frequency (RF) ablation is limited at
      high power by impedance rise when electrode tip temperature exceed 100 degrees C,
      controlling tip temperature by continuous intraelectrode saline infusion could
      permit generation of larger lesion. (1) Two dogs randomly received either
      standard or cooled tip RF ablation at 4 to 6 separate LV sites. Power output of
      30 W was delivered via modified 7 Fr deflectable catheter with 4 mm tip for up to
      120 sec or until impedance rise occurred. (2) Six dogs randomly received cooled
      tip RF ablation at power output of 20, 30, 40 W for 120 sec. (3) Three dogs
      randomly received cooled tip RF ablation using room temperature saline (21-25
      degrees C) or chilled saline (1-4 degrees C) infusion. RESULTS: Overall, peak tip
      temperature was lower for cooled vs standard RF deliveries (97 +/- 17 degrees C
      vs. 42 +/- 8 degrees C). Lesion depth and volume were significantly larger for
      cooled burns. Lesion depth and volume and the incidence of abrupt impedance
      rise/popping did not differ between room temperature saline and chilled saline
      infusion. The catheter-tip temperature at the onset of popping and abrupt
      impedance rise was 54 +/- 5 degrees C (48-60 degrees C) and 59 +/- 10 degrees C
      (50-75 degrees C). CONCLUSION: Cooled tip RF current delivery at high power is
      associated with increased myocardial lesion size which may facilitate successful
      ablation of ventricular tachycardia associated with acquired structural heart
      disease. Catheter-tip temperature should be maintained below 45 degrees C to
      prevent popping and abrupt impedance rise during RF energy delivery.

PMID- 11839879
TI  - Long-term survival following radiofrequency catheter ablation of atrioventricular
      junction for atrial fibrillation: clinical and ablation determinants of
      mortality.
AB  - BACKGROUND: For patients with drug-refractory atrial fibrillation, radiofrequency
      catheter ablation of the atrioventricular junction and pacemaker implantation is
      a nonpharmacologic option routinely used nowadays. Few data are available on the
      long-term survival following the procedure or on evaluation of the risk factors
      for death in a large study cohort. METHODS: The patient population included 359
      subjects undergoing atrioventricular junction ablation and pacemaker insertion.
      Fourteen clinical and 9 ablation variables were collected at baseline. During a
      mean following-up of 40.8 +/- 25.6 months, 46 patients died. Survival probability
      was estimated by the Kaplan-Meier methods. Multivariate Cox proportional hazards
      regression analysis was applied to define predictors of death. RESULTS: Mean age
      was 64.6 +/- 10.6 years with 203 male (57.7%). Actuarial survival probability for
      the total patients was 0.953 and 0.827 at 1 and 5 year. Four clinical variables,
      but no ablation variables, were found to be independent predictors of death: age
      > or =65 year (hazard ratio [HR], 1.92; 95% confidence interval [CI], 1.00-3.69),
      the presence of heart failure (HR, 3.83; 95% CI, 1.87-7.86), coexisting diabetes
      (HR, 2.91; 95% CI, 1.47-5.77), and the value of fractional shortening < or =20%
      (HR, 5.79, 95% CI, 3.00-11.18). There were 20 deaths in 28 patients with > or =3
      risk factors and 4 deaths in 115 patients with no risk factor. CONCLUSION: The
      risk of death in patients undergoing ablation and pacing can be identified by
      readily available clinical variables. Patients with multiple risk factors are
      associated with an increasing mortality.

PMID- 11839880
TI  - Precordial QT dispersion does not predict inducibility of ventricular
      tachyarrhythmias at post-revascularization electrophysiologic study.
AB  - OBJECTIVES: We tested the hypothesis that revascularization would decrease QT
      interval dispersion and that QT interval dispersion would predict the outcome of
      the electrophysiologic study following revascularization. BACKGROUND: QT interval
      dispersion may be a measure of the inhomogeneity of ventricular repolarization.
      The value of the QT interval dispersion for predicting inducibility of
      ventricular tachyarrhythmias (VT) during electrophysiologic studies after
      coronary artery revascularization in patients with hemodynamically significant VT
      is unknown. METHODS AND RESULTS: QT interval dispersions were measured from
      electrocardiograms recorded before and after coronary artery revascularization,
      but before an electrophysiologic study during the same hospitalization. Fifty-six
      patients (93% male, 65.1 +/- 9.6 years) were studied. QT interval dispersion
      decreased significantly following revascularization from 69 +/- 31 ms to 53 +/-
      23 ms (p=0.002). Inducibility of VT could not be predicted by the QT interval
      dispersion following revascularization (50 +/- 30 ms in patients with VT induced
      vs. 58 +/- 25 ms in patients without VT induced at electrophysiologic study;
      p=0.2). The change in QT interval dispersion with revascularization (-15 +/- 33
      ms vs. -17 +/- 46 ms; p=0.9) could not predict VT inducibility. Actuarial
      survival after 80 months follow-up was similar in the patients in whom VT was
      induced (82%) and those patients in whom VT was not induced (83%; p=NS).
      CONCLUSIONS: Coronary artery revascularization decreased QT interval dispersion
      in patients with hemodynamically significant VT, but QT interval dispersion was
      not predictive of inducibility of VT at follow-up electrophysiologic study.
      Actuarial survival was similar in patients in whom VT was induced and patients in
      whom VT was not induced.

PMID- 11839881
TI  - Mechanism of ventricular tachycardia termination by pacing at left ventricular
      sites in patients with coronary artery disease.
AB  - OBJECTIVE: The mechanism by which pacing terminates ventricular tachycardia (VT)
      may depend on the location of the pacing site relative to the reentry circuit.
      The purpose of this study was to compare the mechanisms by which pacing
      terminates VT at left ventricular (LV) sites with and without concealed
      entrainment (CE) in patients with prior myocardial infarction. METHODS AND
      RESULTS: LV mapping was performed in 29 patients (26 men, 3 women, mean age 67 +/
      11 years, ejection fraction 0.28 +/- 0.11) with 55 hemodynamically-tolerated VTs
      (mean cycle length 478 +/- 92 msec). A total of 408 pacing trains were delivered
      at 102 sites with CE. Radiofrequency catheter ablation was successful in 41 of 55
      VT's. At sites with concealed entrainment, VT was terminated by pacing at 17/41
      (41%) successful and at 4/61 (7%) unsuccessful ablation sites (p<0.01).
      Termination without global ventricular capture was the most frequent termination
      mode (10/21), followed by termination with orthodromic (4/21) and non-orthodromic
      capture (7/21). CONCLUSION: In patients with prior myocardial infarction, pacing
      at sites of CE during VT usually terminates VT either without global capture or
      by orthodromic capture. Termination of VT by pacing without global capture or
      with orthodromic capture at sites of CE suggests that the site is within a
      critical area of the reentry circuit.

PMID- 11839882
TI  - Intracardiac echocardiography guided radiofrequency catheter ablation of the slow
      pathway in atrioventricular nodal reentrant tachycardia.
AB  - BACKGROUND: ICE has demonstrated its utility in imaging right atrial structures
      but its utility in slow pathway (SP) ablation has not been documented in a
      randomized trial. METHODS: The feasibility of using ICE as a imaging modality to
      identify the effective site of SP ablation was done in part one of the study
      comprising 10 patients of typical AVNRT. Subsequently, a prospective randomized
      study was done comparing the conventional (group A) and ICE guided (group B)
      ablation of the SP. Each group had 20 patients of typical AVNRT. Ablation in the
      conventional arm was guided by intracardiac electrograms and fluoroscopy. Group B
      patients underwent SP ablation guided primarily by ICE imaging; fluoroscopy was
      used mainly for initial placement of catheters. RESULTS: Reliable & stable ICE
      images were obtained in all patients. Part I of the study showed that RF pulses
      given when the ablation catheter was seen to cross the atrioventricular muscular
      septum (AVMS), always resulted in junctional rhythm. In Group B, RF pulse was
      delivered only when the ablation catheter was at the AVMS making an obtuse angle
      with the image of the His-bundle catheter. Consistent junctional rhythm and
      abolition of SP resulted at this site. Compared to group A, patients in group B
      required fewer pulses (mean 1.4 +/- 0.6 vs. 4.4 +/- 3.0; p < 0.05, median 1 vs.
      5; p < 0.01), achieved a higher temperature (56 +/- 4 degrees C vs. 50 +/- 6
      degrees C) and had more frequent junctional rhythm (100% vs. 70%) during RF
      pulse. CONCLUSIONS: A critical portion of SP exists adjacent to Tricuspid valve
      overlying the AVMS. ICE imaging consistently and reliably localizes this site and
      RF applications here result in interruption of antegrade SP conduction.

PMID- 11839883
TI  - The "window" of slow pathway conduction after ablation and recurrence of
      atrioventricular nodal reentrant tachycardia.
AB  - INTRODUCTION: Slow pathway (SP) conduction often persists following
      radiofrequency (RF) catheter ablation of atrioventricular nodal reentrant
      tachycardia (AVNRT). An association between persistent SP conduction, as
      evidenced by discontinuous AV nodal conduction curves, and recurrent tachycardia
      has not been established. Of note, the segment of the curve attributable to SP
      conduction (the "window" of SP conduction) varies. This study examined whether
      the maximal post-ablation SP conduction window length differs in patients who
      later have recurrent tachycardia when compared with those who do not recur.
      METHODS AND RESULTS: Electrophysiologic study data were compared in two groups
      who had undergone RF ablation of the SP for typical AVNRT at a single center from
      1992-1998. The groups, consisting of seven known recurrences (Group A) and 50 non
      recurrences confirmed through a follow-up survey and phone contact (Group B),
      were similar in gender proportion, age, baseline electrophysiologic data, and
      number of RF deliveries. Four patients (57%) from Group A and 26 (52%) from Group
      B exhibited discontinuous AV nodal conduction curves after ablation. The maximum
      post-ablation window lengths among patients with dual AV nodal physiology varied
      widely and similarly in the two groups, and the means did not significantly
      differ (53 +/- 47 msec in Group A vs. 36 +/- 31 msec in Group B; p=0.36).
      CONCLUSION: Persistent SP conduction post-ablation in this series was a common
      finding not predictive of recurrence. No difference in the maximum SP conduction
      window post-ablation was evident between recurrences and non-recurrences.

PMID- 11839884
TI  - Radiofrequency catheter ablation for intra-atrial reentrant tachycardia after
      surgery of atrial septal defect: use of isopotential mapping (QMS system) to
      demonstrate bidirectional complete block.
AB  - A 51 year-old Japanese man who had undergone surgical correction of an atrial
      septal defect at the age of 18 years old was referred to our institute for
      evaluation of his atrial arrhythmia. The conventional electrophysiological study
      was combined with a new technique utilizing an isopotential and isochronal
      mapping system (QMS) to visualize the electrical signals recorded with a 64
      electrode basket catheter. Using this system, an intra-atrial reentrant
      tachycardia (IART) was demonstrated. The isopotential map recorded with the QMS
      (QMS-isoP) rapidly revealed a clockwise global reentrant circuit in the mid free
      wall of the right atrium and a narrowest activation isthmus between the lower end
      of the atriotomy scar and the inferior vena cava (IVC). After confirming
      entrainment with concealed fusion at the lower end of the atriotomy scar,
      radiofrequency energy was delivered linearly from this site to the IVC by slowly
      dragging the catheter. The elimination of the IART was defined by the QMS-isoP
      which demonstrated bidirectional block during pacing from both sides of the
      ablated linear lesion. The conventional technique of entrainment with concealed
      fusion combined with the QMS-isoP may result in a highly sophisticated method for
      identifying global reentrant circuits and for defining bidirectional block after
      eliminating the IART.

PMID- 11839885
TI  - Significance of stimulation impedance in biventricular pacing.

PMID- 11839886
TI  - Left heart pacing--experience with several types of coronary vein leads.
AB  - Our experience with 121 coronary vein (CV) leads in 116 patients shows that CV
      leads are the leads of choice for pacing the left ventricle (LV). The information
      gained from pre-operative venous angiography permits individual selection of the
      most appropriate lead model for each case. The use of steerable electrophysiology
      catheters facilitates guide catheter cannulation of the coronary sinus (CS) when
      the anatomy is difficult and reduces the risk of complications. By selecting the
      CV lead model most suitable for each individual patient, we achieved successful
      implantation in 99.1% of patients. In this day and age, epicardial electrodes
      should be restricted to cases with CS anomalies which make CS cannulation
      impossible, and to LV lead implantation during heart surgery.

PMID- 11839887
TI  - Far-field P-wave sensing by the right ventricular lead of conventional dual
      chamber pacemakers.
AB  - This report describes two cases of far-field sensing of the P wave by the
      ventricular channel of conventional DDD pacemakers programmed to a relatively
      high sensitivity to promote sensing of ventricular extrasystoles. Ventricular
      pacing was maintained in both cases when the ventricular channel was not
      inhibited. One case was caused by displacement of a bipolar ventricular lead
      towards the right ventricular inflow tract. The other case occurred only in
      relation to an atrial extrasystole in the absence of ventricular lead
      displacement.

PMID- 11839888
TI  - Short and medium time experience with a tined, multilumen steroid eluting
      defibrillation lead.
AB  - Both leads and pulse generators of implantable defibrillators have undergone
      important improvements during the last years. New leads should be tested against
      previous models to demonstrate safety and reliability. When introduced in 1995,
      the Medtronic 6932 pace, sense and defibrillation lead was compared to the
      alternative larger 6936 lead in a short-term randomized study with a mean follow
      up of 2.4 +/- 2.0 months. A subgroup of patients were followed for 23.9 +/- 9.0
      months. Three hundred and thirty-six patients were randomized to receive either
      the 6932 or the 6936 lead. Defibrillation threshold at implant, tested using a
      binary search protocol, was similar for the two leads. The pacing threshold was
      significantly lower for the 6932 lead both at implant and at follow-up, probably
      due to the steroid eluting tip of the electrode. R-wave amplitudes were similar
      for the leads, as were the complication rates. During about two years of follow
      up, both leads performed well, with a slightly lower pacing threshold for the
      6932 lead.

PMID- 11839889
TI  - Innovative endovascular defibrillator lead use in superior vena cava obstruction.
AB  - BACKGROUND: We describe an unusual case of severe heart failure (HF) and rapid
      atrial fibrillation (AF) improved through ablation and pacemaker implant despite
      superior vena cava obstruction (SVCO). METHODS: SVCO precluded upper body venous
      access to the heart for procedural rate control. Both AV Junctional ablation and
      permanent endovascular lead placement were achieved through the inferior vena
      cava (IVC). RESULTS: Clinical improvement from NYHA Class IV to Class II HF was
      observed with effective nonpharmacologic ventricular rate control. CONCLUSIONS:
      HF patients with rapid AF and SVCO can achieve ventricular rate control through
      lower body venous access to the heart utilizing 100-cm endovascular defibrillator
      rate sensing leads.

PMID- 11839894
TI  - Management of the agitated intensive care unit patient.

PMID- 11839890
TI  - Electrical storms in an ICD-recipient with 429 delivered appropriate shocks:
      therapeutic management with antiarrhythmic drug combination.
AB  - The case of a 65 year old man with ischemic cardiomyopathy, an ICD device and
      recurrent electrical storms is presented. The patient had been implanted with an
      ICD device due to aborted sudden death. The first electrical storm occurred 12
      months later. It was terminated by the administration of intravenous amiodarone
      and the patient was discharged on maintenance dose amiodarone and b-blocker.
      After a period of 3 months during which the patient remained asymptomatic, a
      second arrhythmic clustering occurred and it was controlled by the addition of
      mexiletine. A total number of 429 appropriate shocks had been delivered by the
      device. Thereafter and for a seven month follow-up period, the patient remains
      asymptomatic under this combination of antiarrhythmic drugs.

PMID- 11839891
TI  - Marcus Gerbezius (1658-1718).

PMID- 11839895
TI  - POST-TEST.

PMID- 11839897
TI  - Generational tension among nurses.

PMID- 11839900
TI  - Menorrhagia and hysterectomy.

PMID- 11839903
TI  - The political action committee.

PMID- 11839899
TI  - Lack of pain management.

PMID- 11839904
TI  - Osteoporosis.

PMID- 11839905
TI  - Preventing air embolism.

PMID- 11839906
TI  - Bronchial hygiene therapy.

PMID- 11839907
TI  - Body Language: Melting pain into song.

PMID- 11839908
TI  - Emergency and disaster preparedness: core competencies for nurses.

PMID- 11839909
TI  - Book of the year awards.

PMID- 11839910
TI  - Pain in the critically ill.

PMID- 11839911
TI  - APRNs fight for their right to practice.

PMID- 11839912
TI  - Street nursing.

PMID- 11839913
TI  - The 'hygiene hypothesis: how clean should we be?

PMID- 11839914
TI  - Nursing care providers in home care: a shortage of nonprofessional, direct care
      staff.

PMID- 11839916
TI  - Counting nurse practitioners.

PMID- 11839917
TI  - Dare to imagine. A nurse adds health care and other concerns to NOW's agenda.
      Interview by Thomas Schwarz.

PMID- 11839918
TI  - JCAHO becomes a force in needlestick prevention.

PMID- 11839919
TI  - Media News: Received 12/01.

PMID- 11839920
TI  - Planting the future for nursing.

PMID- 11839921
TI  - Clinical nurse specialists as research team members.

PMID- 11839922
TI  - A theory-based clinical nurse specialist practice exemplar using Neuman's systems
      model and nursing's taxonomies.
AB  - This article illustrates the process of theory-based advanced nursing practice by
      presenting an exemplar of clinical nurse specialist practice using Neuman's
      systems model and nursing's taxonomies. A brief explanation of Neuman's systems
      model is given, and the process of assessment, diagnosis, and planned
      outcomes/interventions is fully described. A clinical example illustrates the
      entire process.

PMID- 11839923
TI  - Clinical nurse specialist participation in an epidemiologic study: implications
      for practice.
AB  - The purpose of this article is to describe clinical nurse specialist
      participation in an epidemiologic study. The population under investigation
      comprised participants with malignant brain tumors, a population the clinical
      nurse specialist has served for the past 14 years. During the study, each
      clinical nurse specialist role was used. The clinical nurse specialist was
      instrumental in soliciting participation and ensuring complete and accurate data.

PMID- 11839924
TI  - The need for more clinical research.

PMID- 11839925
TI  - Fibromyalgia: patient perspectives on symptoms, symptom management, and provider
      utilization.
AB  - Two surveys of individuals with fibromyalgia were conducted to assess the
      frequency and prevalence of symptoms (N = 99) as well as healthcare providers,
      medications, and self-care activities used to manage one's fibromyalgia (N = 54).
      The pervasiveness of symptoms was striking, with 24 various symptoms ranging from
      cognitive to intestinal problems occurring in at least 75% of the respondents.
      Significant correlations were present between health status and both physical (P
      = .002) and psychological (P =.008) symptoms. There was also a significant
      correlation between the total number of symptoms and the degree of life
      disruption attributed to fibromyalgia (P =.015). A variety of healthcare
      professionals were seen, with internists, family physicians, and rheumatologist
      most frequently used. Although at least 80% of the respondents reported
      difficulty with anxiety, confusion, irritability, depression, and cognitive
      difficulties, less than 10% of the respondents reported seeing a psychiatrist.
      Most frequently used medications were: amitriptyline, (fluoxetine HCl) Prozac,
      ibuprofen (Motrin), sertraline HCI (Zoloft), and zolpidem (Ambein). Self-care
      activities used with the most success were walking, stretching, and exercising.
      These studies indicate the need for more research and support for healthcare
      providers as well as patients with fibromyalgia.

PMID- 11839926
TI  - Collective and individual sorrow.

PMID- 11839927
TI  - Intimate strangers.

PMID- 11839928
TI  - What to look for when analyzing clinical nurse specialist statutes and
      regulations.

PMID- 11839929
TI  - Considerations for postoperative pain management in older adults.

PMID- 11839930
TI  - Personal digital assistants: a world of information in the palm of your hand.

PMID- 11839931
TI  - Why do nurses see families as "trouble?".

PMID- 11839932
TI  - Chaos and self-organization as a consequence of spiritual disequilibrium. 1996.

PMID- 11839937
TI  - Managing Information in Healthcare: Concepts and Cases.

PMID- 11839936
TI  - Collaboration with psychiatrists in Connecticut.

PMID- 11839938
TI  - Medi-Sim Multimedia: AACN Critical Care-Hematological System.

PMID- 11839939
TI  - Toll-like receptors.
AB  - The ability of a host to sense invasion by pathogenic organisms and to respond
      appropriately to control infection is paramount to survival. In the case of
      sepsis and septic shock, however, an exaggerated systemic response may, in fact,
      contribute to the morbidity and mortality associated with overwhelming
      infections. The innate immune system has evolved as the first line of defense
      against invading microorganisms. The Toll-like receptors (TLRs) are a part of
      this innate immune defense, recognizing conserved patterns on microorganisms.
      These TLRs and their signaling pathways are represented in such diverse creatures
      as mammals, fruit flies, and plants. Ten members of the TLR family have been
      identified in humans, and several of them appear to recognize specific microbial
      products, including lipopolysaccharide, bacterial lipoproteins, peptidoglycan,
      and bacterial DNA. Signals initiated by the interaction of TLRs with specific
      microbial patterns direct the subsequent inflammatory response. Thus, TLR
      signaling represents a key component of the innate immune response to microbial
      infection.

PMID- 11839940
TI  - Carbon monoxide-dependent signaling.
AB  - It has become accepted that nitric oxide serves important functions in biological
      systems as a second messenger. Another diatomic gaseous molecule, carbon monoxide
      (CO), is also rapidly gaining acceptance as a signaling agent. Some of the
      activities of CO are analogous to those of nitric oxide in the vascular system
      and the brain, but CO also behaves in novel ways. Like nitric oxide, CO is
      capable of activating soluble guanylyl cyclase. This mechanism of CO signaling is
      important in vasodilation and neurotransmission. There is growing evidence,
      however, that CO also acts independently of soluble guanylyl cyclase. CO has been
      shown to protect against septic shock and lung injury in animal models, and the
      mitogen-activated protein kinase system appears to mediate this cytoprotective
      effect. Although much remains to be elucidated about the mechanisms of cell
      signaling by CO, the pace of discovery in this field is making the picture
      clearer with every passing day.

PMID- 11839944
TI  - Heat shock factor 1 and heat shock proteins: Critical partners in protection
      against acute cell injury.
AB  - OBJECTIVE: Life-threatening conditions cause severe changes in the organization
      and conformation of macromolecules, creating urgent requirements for protein
      repair to ensure survival. As molecular chaperones, heat shock proteins (HSP)
      that have specialized functions in protein folding are now well established to
      restore homeostasis in cells and organisms. Augmentation of HSP synthesis is
      tightly regulated by stress-inducible heat shock factors (HSF), which are part of
      a transcriptional signaling cascade with both positive (e.g., HSP) and negative
      (e.g., proinflammatory cytokines) properties. In this review, we discuss the
      biological roles and mechanisms of HSP-mediated protection in pathophysiologic
      conditions (ischemia, sepsis, and preeclampsia) and the regulation for stress
      dependent HSP synthesis and speculate about future applications for harnessing
      HSF and HSP partners as cytoprotective agents. DATA SOURCES: Reactive oxygen
      species are major pathogenic factors in cell death pathways (e.g., necrosis,
      apoptosis), in part, because of proteotoxic effects. In intact organisms, forced
      overexpression of HSP per se affords effective counterbalance against ischemia
      challenges (e.g., heart and brain) and systemic conditions (e.g., sepsis).
      Besides stressful conditions, gene-targeting studies have uncovered new functions
      for heat shock transcription factors (e.g., maintenance of intrauterine
      pregnancy) in mammals. In parallel, pharmacologic studies using small molecules
      are paving the way for future prospects to exploit the beneficial properties of
      HSP, albeit an important but presently elusive goal. CONCLUSIONS: Together, HSF
      and HSP partners are attractive targets in therapeutic strategies designed to
      stimulate endogenous protective mechanisms against deleterious consequences of
      oxidative stress. With further technological advances, it is anticipated that the
      spotlight on HSP, alone or in combination with other stress response pathways,
      could, ultimately, reduce injury and accelerate functional recovery of
      susceptible organs in living organisms including humans.

PMID- 11839945
TI  - Functional genomics of critical illness and injury.

PMID- 11839946
TI  - Interleukin-10: A complex role in the pathogenesis of sepsis syndromes and its
      potential as an anti-inflammatory drug.
AB  - Interleukin (IL)-10 is a pleiotropic cytokine produced by both T cells and
      macrophages and possesses both anti-inflammatory and immunosuppressive
      properties. IL-10 circulates in the blood of patients with sepsis syndromes, and
      increased concentrations of IL-10 have been associated with an adverse clinical
      outcome. Experimental studies in rodents and primates have demonstrated that
      endogenously produced and exogenously administered IL-10 can reduce the magnitude
      of the inflammatory response and improve outcome, primarily in models of
      endotoxemic and bacteremic shock. However, endogenous IL-10 production and
      systemic administration can also exacerbate T-cell dysfunction, decrease T-cell
      apoptosis, reduce antimicrobial function, and increase mortality in other less
      acute bacterial models of sepsis or after thermal injury. Targeted delivery of IL
      10 to individual tissues may obviate the adverse effects of systemic delivery.
      The potential anti-inflammatory properties of IL-10 will have to be carefully
      weighed against its immunosuppressive properties when considering its use in
      patients with acute inflammation and sepsis syndromes.

PMID- 11839951
TI  - Structural brain abnormalities in adult males with clefts of the lip and/or
      palate.
AB  - PURPOSE: To evaluate brain morphology of adult males with nonsyndromic clefts of
      the lip and/or palate (NSCLP) in comparison to a matched healthy control group.
      METHODS: Brain structure was measured using quantitative analysis of magnetic
      resonance images. RESULTS: Subjects with NSCLP had significant abnormalities in
      brain morphology consisting of abnormally enlarged anterior regions of the
      cerebrum, and decreased volumes of the posterior cerebrum and cerebellum.
      Overall, the most severely affected region was the left temporal lobe.
      Furthermore, these structural abnormalities were directly related to cognitive
      dysfunction. CONCLUSIONS: These findings highlight the important relationship and
      interplay between face and brain development.

PMID- 11839952
TI  - Pilot assessment of the subtelomeric regions of children with autism: detection
      of a 2q deletion.
AB  - PURPOSE: Autism is a chronic neurodevelopmental disorder characterized by
      deficits in reciprocal social interaction, language and communication, and by the
      presence of stereotypical behaviors. The disorder is a complex genetic trait with
      no known predisposing genes. We report the results of a pilot project to screen
      for aberrations in the gene-rich subtelomeric chromosomal regions of a cohort of
      children with autism. METHODS: For our pilot project, we used a multiprobe system
      that includes probes for the subtelomeric regions of all human chromosomes. We
      assessed the subtelomeric regions of chromosomes from 10 children with a
      diagnosis of autism. RESULTS: The screen identified one child with an apparent
      deletion of the subtelomeric region of chromosome 2q; nine children and pooled
      control samples yielded normal results. The deletion in our patient was confirmed
      with two other subtelomeric probes and a targeted cytogenetic study revealed a
      subtle difference in appearance for one chromosome 2 homologue. CONCLUSION: There
      have been several reports of children with dysmorphic features, autistic
      behaviors, and 2q deletions detectable with standard cytogenetic techniques. It
      may be that the distal region of chromosome 2q harbors a gene or genes that may
      predispose to autism.

PMID- 11839953
TI  - Molecular characterization of 18p deletions: evidence for a breakpoint cluster.
AB  - PURPOSE: To determine the size and parental origin of the deletion in individuals
      with 18p- syndrome. METHODS: Molecular and fluorescence in situ hybridization
      analyses of the pericentromeric region of chromosome 18 were performed on genomic
      DNA and chromosomes from study participants. RESULTS: The majority of the
      breakpoints were located between markers D18S852 on 18p and D18S1149 on 18q, a
      distance of approximately 4 Mb. The parental origin of these deletions appears to
      be equally distributed, half maternally derived and half paternally derived.
      CONCLUSION: The distributions of both the size and parental origin of the 18p
      deletions support the presence of a breakpoint cluster in the 18p- syndrome.

PMID- 11839954
TI  - Molecular analysis of spinal muscular atrophy and modification of the phenotype
      by SMN2.
AB  - PURPOSE: This study describes SMN1 deletion frequency, carrier studies, and the
      effect of the modifying SMN2 gene on the spinal muscular atrophy (SMA) phenotype.
      A novel allele-specific intragenic mutation panel increases the sensitivity of
      SMN1 testing. METHODS: From 1995 to 2001, 610 patients were tested for SMN1
      deletions and 399 relatives of probands have been tested for carrier status. SMN2
      copy number was compared between 52 type I and 90 type III patients, and between
      type I and type III patients with chimeric SMN genes. A fluorescent allele
      specific polymerase chain reaction (PCR) -based strategy detected intragenic
      mutations in potential compound heterozygotes and was used on 366 patients.
      RESULTS: Less than half of the patients tested were homozygously deleted for
      SMN1. A PCR-based panel detected the seven most common intragenic mutations. SMN2
      copy number was significantly different between mild and severely affected
      patients. CONCLUSIONS: SMN1 molecular testing is essential for the diagnosis of
      SMA and allows for accurate carrier testing. Screening for intragenic mutations
      in SMN1 increases the sensitivity of diagnostic testing. Finally, SMN2 copy
      number is conclusively shown to ameliorate the phenotype and provide valuable
      prognostic information.

PMID- 11839955
TI  - Presymptomatic diagnosis for children of sporadic neurofibromatosis 2 patients: a
      method based on tumor analysis.
AB  - PURPOSE: To provide presymptomatic diagnosis for children of sporadic
      neurofibromatosis 2 patients in whom no NF2-mutations were found by screening
      their blood-DNA. METHODS: Tumors of four patients were analyzed for NF2 allele
      losses and mutations. RESULTS: Nonsense NF2 mutations and NF2 allele losses were
      found in all tumors. None of these alterations was found in any of eight children
      examined, suggesting that these children did not inherit the disease.
      CONCLUSIONS: Finding two genetic alterations of a tumor suppressor gene in
      associated tumors is useful for presymptomatic diagnosis. Identification of the
      lost allele in tumors alone also enables exclusion of disease transmission in 50%
      of cases.

PMID- 11839958
TI  - Happy Birthday to HHN!

PMID- 11839956
TI  - Mapping the human genome: an assessment of media coverage and public reaction.
AB  - PURPOSE: To assess public reactions to the June 26, 2000, announcement that
      scientists had nearly finished mapping the human genome. METHODS: We conducted a
      random-digit telephone survey of 407 Maryland residents as well as a content
      analysis of 55 relevant media reports. RESULTS: African Americans were more
      likely than Caucasians to report a negative reaction (P < 0.001) to the genome
      announcement. Overall, privacy/discrimination (16%) and human cloning (14%) were
      the most commonly mentioned concerns regarding the impact of the genome mapping.
      CONCLUSIONS: These findings highlight the need for continued public discourse,
      including through the media, to address concerns regarding the Human Genome
      Project.

PMID- 11839960
TI  - Growing your own CNAs: it's worth the effort.
AB  - Shortages in healthcare workers are projected to continue for the next few years.
      This article presents a "how- to" for organizations to attract applicants and
      develop an in-house training program for Certified Nurse Assistants (CNAs). The
      process Saint Anthony's Health Center had in executing an in-house certification
      program and the positive outcome experienced are presented.

PMID- 11839959
TI  - Electronic clinical records: what do regulators want?
AB  - Agencies that are adopting electronic medical records systems must be clear about
      the various issues surrounding this type of technology. This article clarifies
      the five areas that providers and surveyors have considered as important in
      assuring compliance while using these systems.

PMID- 11839961
TI  - Multidrug resistant organisms--VRE and MRSA: practical home care tips.

PMID- 11839962
TI  - Caring for the patient who has undergone female circumcision.
AB  - Home health and hospice nurses are increasingly called to care for patients the
      world over. The provision of culturally competent and culturally sensitive care
      is critical to patient care planning. Viewing the patient holistically and within
      the context of family and culture provides the basis of most effective care.
      While nurses may not be providing skilled care directly related to female
      circumcision, it is important to include all of the patient's concerns within the
      framework of a comprehensive plan of care.

PMID- 11839963
TI  - Teaching self-management of diabetes via telehomecare.
AB  - This study demonstrates that telehomecare is an effective way to improve patient
      education and self-management outcomes. The cost effectiveness of this technology
      makes it an attractive medium for reaching patients who require close monitoring,
      reinforced teaching, and reassurance. telehomecare can also support caregivers
      and connect socially isolated individuals to their care providers. The
      possibilities for using telehomecare are just beginning to be realized. With the
      advent of PPS, telehomecare may be an effective substitute for visits that focus
      on teaching and monitoring. It is a new tool in the arsenal for the home care
      nurse to use for monitoring patients and promoting knowledge and behavior change.
      The video visits are short, focused opportunities for increased patient teaching;
      the one-on-one focus, audio-visual aids, and opportunities for patients to use
      the machines to self-monitor are all positive aspects.

PMID- 11839964
TI  - How expert home care nurses recognize early client status changes.

PMID- 11839965
TI  - A competency-based modular learning program.
AB  - This article describes a take-home competency-based modular learning system that
      includes posttesting and a hands-on competency validation. This successful
      program assisted in improving nursing skills, nurse satisfaction, and quality of
      care. Although used with pediatric clinicians, this program can be adapted to any
      type agency or staff competencies.

PMID- 11839966
TI  - Medicare Part B negative pressure wound therapy pump policy. A partner for
      Medicare Part A PPS.

PMID- 11839967
TI  - Academic and educational partnerships can work for you.
AB  - These partnerships are not merely a survival tactic. Thriving and progressive
      leaders spawn the creativity needed to accomplish great tasks through collective
      dialogue and mutual goals. Academic and educational partnerships can work for
      you!

PMID- 11839968
TI  - CHAP basics.
AB  - The CHAP accreditation process was established to provide an objective, external
      process for evaluating an organization's effectiveness in meeting its own
      mission, while the organization was providing services that meet national care
      standards. The entire CHAP review process is based on a nursing model of care-
      that of organizational assessment, strength and weakness identification,
      appropriate organizational interventions, and evaluation that provides a holistic
      approach to an organization's performance. CHAP expects to see a home care or
      hospice organization providing effective services that are appropriate for the
      patient population and communities it serves.

PMID- 11839969
TI  - The Benefits of Certification as a Clinical Specialist in Home Health Nursing.

PMID- 11839970
TI  - Structure, process, and outcome.

PMID- 11839971
TI  - American Heart Association issues new dietary guidelines.

PMID- 11839972
TI  - 2002 legislative update.

PMID- 11839973
TI  - Professional boundaries in the home care setting.

PMID- 11839974
TI  - Contracted home care and hospice services: who's surveyed and who's exempt.

PMID- 11839976
TI  - Assessing & preventing medication interactions.
AB  - The use of multiple drugs to treat medical conditions has become a common
      practice that significantly increases the risk of drug interactions.This article
      describes three types of drug interactions by clarifying how these occurrences
      transpire within the body. Practical strategies for preventing drug interactions
      are provided.

PMID- 11839977
TI  - Family caregiving at home.
AB  - PPS has demanded that we teach caregivers to assist while receiving home care and
      upon discharge. This article focuses on what home care nurses need to know to
      adequately prepare families for the caregiving experience. Specific strategies
      for efficiently facilitating caregiver support including assessment, specific
      problems, and resource and referral suggestions are addressed.

PMID- 11839975
TI  - Creative use of ergonomic principles in home care.
AB  - Although the OSHA Ergonomics Standard was repealed this year, home care agencies
      and visiting staff should be conscious of the issues surrounding workplace
      safety. This article explains ergonomic terms and applies them to situations home
      care staff encounter daily. Helpful ideas to prevent these injuries support
      thinking in new ways to prevent injuries.

PMID- 11839978
TI  - Case conferencing for wound care patients.
AB  - This article identifies elements for the successful management of wound care
      patients in home health via the use of the case conference. Recommendations for
      use of certified wound specialists, identification of criteria for case review,
      and specific questions to address during the case conference review of wound care
      patients are all detailed.

PMID- 11839981
TI  - Hearing screening.

PMID- 11839979
TI  - A telehealthcare primer for managers.
AB  - Managers must know as much as possible about telehealth and its uses in home
      care. This article gives an overview of the technology and how it is changing
      home care practice and management.

PMID- 11839983
TI  - Problems with OASIS remain despite training.

PMID- 11839992
TI  - Efficacy of diaphragmatic breathing in persons with chronic obstructive pulmonary
      disease: a review of the literature.
AB  - The evidence base for diaphragmatic breathing (DB) as an adjunctive treatment
      modality for persons with COPD is questionable. This article reviews the
      literature regarding the efficacy of DB in persons with chronic obstructive
      pulmonary disease (COPD), and reports on the beneficial and detrimental effects
      of DB in persons with COPD. Diaphragmatic breathing has been described as
      breathing predominantly with the diaphragm while minimizing the action of
      accessory muscles that may assist with inspiration. No single or combined patient
      characteristic has been identified consistently to help predict which person with
      COPD may benefit from DB. However, it has been suggested that persons with
      moderate to severe COPD and marked hyperinflation of the lungs without adequate
      diaphragmatic movement and increase in tidal volume during DB may be poor
      candidates for instruction in DB. Conversely, persons with COPD who have elevated
      respiratory rates, low tidal volumes that increase during DB, and abnormal
      arterial blood gases with adequate diaphragmatic movement may benefit from DB.
      Identification of an abdominal paradoxical breathing pattern and worsening
      dyspnea and fatigue during or after DB are criteria to modify or terminate DB.
      Persons with COPD demonstrating an abdominal paradox during DB may benefit from a
      more upright body position or trunk flexion. Several methods to examine
      diaphragmatic movement and the potential for success with DB will be discussed.
      Future research is needed to better identify which patients may benefit from DB.

PMID- 11839993
TI  - Number needed to treat in cardiac rehabilitation.
AB  - Clinicians, patients, and health policy-makers must judge whether healthcare
      interventions are worth the side effects, inconvenience, and costs. The number
      needed to treat (NNT) provides an estimate of the number of patients who need to
      be treated to attain an additional favorable outcome, or to prevent an additional
      adverse outcome, and is the reciprocal of the absolute risk reduction. The closer
      the NNT is to 1.0-meaning that every patient who is treated achieves a benefit
      the more effective the treatment. Traditionally, mortality has been considered a
      primary outcome measure of the effectiveness of cardiac rehabilitation and, if
      the event rates in two groups (ie, rehabilitation and usual care) are known, the
      absolute risk reduction can be calculated and the NNT estimated. Mortality data
      were derived from three meta-analyses of cardiac rehabilitation trials: one
      published in 1988 (n = 3614), one in 1989 (n = 4247), and one in 2001 (n = 7683).
      The respective estimated NNT for mortality in the meta-analyses were 32, 46, and
      72 (95% confidence intervals [95% CI] 19, 1403). Improved exercise tolerance and
      patient-perceived health-related quality of life (HRQL) are also considered
      important and attainable outcomes of cardiac rehabilitation but are continuous,
      not dichotomous, variables. If the minimal important difference for a continuous
      outcome is known, then the proportions of patients who improve, remain the same,
      or deteriorate can be determined and the NNT estimated. Exercise tolerance and
      HRQL data from two randomized controlled trials of 8 weeks of rehabilitation
      after myocardial infarction, the Cardiac Rehabilitation in Advanced Age trial (CR
      AGE; n = 270) and the McMaster Early Rehabilitation Study (MERS; n = 201) were
      used to estimate the NNT. In CR-AGE, the improvement in exercise tolerance was
      significantly greater in the rehabilitation than usual care group and the
      estimated NNT was 5 (95% CI 3, 13). The generic global HRQL score increased
      significantly in CR-AGE with rehabilitation with an estimated NNT of 12 (95% CI
      5, 26) but, as the subscale group differences were not significant, the NNT was
      not estimated. The NNT for exercise tolerance was not estimated in MERS, as the
      group difference was not significant. On the other hand, specific HRQL scores in
      MERS increased significantly with rehabilitation giving an estimated NNT for
      global HRQL of 6 (95% CI 3, 21) and 6 to 10 for the HRQL sub-scales. The data and
      the estimated NNT from the meta-analyses of cardiac rehabilitation in large
      numbers of patients suggest a limited mortality effect, probably reflecting
      current cardiology practice. The estimated NNT from the two trials with
      relatively small numbers of patients suggest inconsistent exercise tolerance
      effects and a relatively short duration for improved HRQL. Along with the classic
      reporting scales, information about clinical and laboratory variables, and
      patient preferences, the NNT is a useful additional measure of effectiveness that
      provides both clinicians and patients with information about the impact of
      cardiac rehabilitation as secondary prevention therapy.

PMID- 11839994
TI  - Thermoregulatory responses in post-coronary artery bypass surgery and healthy
      males during moderate exercise in warm and cool environments.
AB  - PURPOSE: The purpose of this study was to determine and compare the
      thermoregulatory and hemodynamic responses to moderate intensity exercise (60% of
      peak oxygen consumption [.VO(2peak)]) in warm (35 degrees C, 45% relative
      humidity) and cool (18 degrees C, 65% relative humidity) environments in men who
      had previously undergone coronary artery bypass graft (CABG) surgery and healthy
      control subjects, matched for age and body composition. METHODS: Fourteen post
      CABG men and 16 healthy control subjects were recruited and walked 40 minutes at
      a moderate intensity, in randomized order, in warm and cool environments (on
      separate days). Measures of heart rate, systolic and diastolic blood pressures,
      rating of perceived exertion, core (rectal)(T(c)) and mean skin temperatures
      (T(sk)), oxygen consumption (.VO(2peak)), sweat rate, and blood lactate were
      taken. RESULTS: Both groups showed a larger increase (P <.05) in T(c) and rate
      pressure product during exercise in the warm compared with the cool environment.
      However, T(c) and rate pressure product were significantly lower (P <.05), and
      systolic blood pressure decreased slightly with exercise duration (P <.05) in the
      CABG group compared with the control group in the warm environment. Heart rate,
      T(sk), percent .VO(2peak), blood lactate, sweat rate, and rating of perceived
      exertion did not differ significantly between the groups in either climate and no
      subject had ischemia or arrhythmia during test procedures. CONCLUSIONS: These
      results indicate that clinically stable men with revascularized coronary artery
      disease are able to cope as well as healthy controls with the thermoregulatory
      and cardiovascular demands of 40 minutes of moderate intensity exercise in warm
      and cool environments.

PMID- 11839995
TI  - Thermoregulation in patients with cardiac disease.

PMID- 11839996
TI  - Psychological predictors of adherence and outcomes among patients in cardiac
      rehabilitation.
AB  - PURPOSE: The purpose of this study was to evaluate the effects of optimism,
      depression, and neuroticism on adherence and outcomes among patients in cardiac
      rehabilitation (CR). METHODS: Participants included 46 patients (34 men) with
      coronary heart disease (CHD) who completed measures of psychological functioning
      (optimism, depression, neuroticism), physical functioning (exercise stress test,
      body mass index, symptom reports), and CHD knowledge during the first week
      (baseline) and last week of a 12-week CR program. RESULTS: Baseline depression
      scores accounted for 9.5% of the variance associated with change in aerobic
      capacity (maximum oxygen consumption), when controlling for relevant demographic
      variables and program attendance. However, optimism and neuroticism were not
      predictive of CR outcomes. Results also indicated that program dropouts were
      significantly younger and reported more psychological distress at baseline than
      did participants who completed the program. CONCLUSION: Depression appears to
      have a significant influence on adherence and improvement among patients in CR,
      but optimism and neuroticism were not significant predictors of change.

PMID- 11839997
TI  - Why don't we ask patients with coronary heart disease directly how much they have
      changed after treatment?

PMID- 11839999
TI  - Editorial.

PMID- 11840000
TI  - Infusion Nurses Society Position Paper.
AB  - The Infusion Nurses Society (INS) recognizes the right of patients to appropriate
      assessment and management of pain. All patients, regardless of practice setting,
      should have their pain adequately assessed and effectively managed by competently
      trained nurses. Infusion nurse specialists often provide or maintain the avenue
      for access and have the skill and expertise to assess and administer pain
      therapies as prescribed.

PMID- 11840001
TI  - Test Your Knowledge: Preparing to Take the CRNI Exam.
AB  - The CRNI Certification Examination consists of 200 multiple-choice questions
      covering the nine core content areas of infusion nursing: Technology and Clinical
      Applications, Fluid and Electrolyte Balance, Pharmacology, Infection Control,
      Pediatrics, Transfusion Therapy, Antineoplastic Therapy, Parenteral Nutrition,
      and Quality Assurance. The review questions provided below are modeled on the
      CRNI exam and are intended to help exam candidates test their knowledge of
      infusion therapy practice. This special section is a regular addition to the
      Journal of Infusion Nursing, with each edition focusing on a single content area.

PMID- 11839998
TI  - The flutter device and expiratory pressures.
AB  - PURPOSE: Flutter therapy uses a handheld instrument that consists of a pipe-like
      device with a ball in the central core that oscillates during exhalation,
      providing oscillating positive expiratory pressure. The purpose of this study was
      to determine the effect of airflow and the incline of the device at the mouth on
      expiratory pressure and oscillation frequency. METHODS: A Flutter device was
      attached to a circuit that consisted of a pneumotachograph and a ventilator. The
      ventilator generated different flows and expiratory pressure was measured with a
      pressure transducer. The angles considered were +40 degrees to -40 degrees in
      increments of 10 degrees , with the reference for incline being the horizontal
      line. Expiratory pressure, airflow, angle of incline, and oscillation frequency
      were measured. RESULTS: There was a strong and significant correlation between
      flow and expiratory pressure at each level of incline (P < or =006; r > 0.93).
      There also was a significant and strong correlation between expiratory pressure
      and oscillation frequency (P <.05; r = 0.81-0.97). There was a significant
      reduction in expiratory pressure at a negative incline of -40 degrees.
      CONCLUSIONS: The results of this study indicate that a positive incline and a
      large airflow result in an increase in expiratory pressure. This information will
      assist clinicians to better understand the effects of the Flutter device.

PMID- 11840002
TI  - Parenteral nutrition in hepatic, biliary, and renal disease.
AB  - Providing nutritional support for patients with liver, biliary, pancreatic, or
      renal disease can be challenging because of the complexity associated with the
      underlying disease state. Parenteral nutrition interventions should be determined
      using sound, evidence-based practice recommendations, not based on tradition.
      This article discusses the current evidence-based practice guidelines for
      providing parenteral nutrition formula modification to patients with liver,
      biliary, pancreatic or renal disease.

PMID- 11840003
TI  - Central venous catheter infections. Clinical aspects of microbial etiology and
      pathogenesis.

PMID- 11840004
TI  - Metabolic complications associated with parenteral nutrition.
AB  - Parenteral nutrition is an accepted medical therapy for individuals with
      gastrointestinal tract dysfunction. It also uses one of the most complex
      intravenous solutions, which contains all the nutrients needed for a patient's
      nutritional requirements. Metabolic complications may result from intolerance of
      glucose, overfeeding, electrolyte shifts, and fluid imbalances. This article
      describes how to anticipate, identify, and treat such complications so they do
      not become life threatening.

PMID- 11840006
TI  - Parenteral nutrition focus. Nutrition assessment and formula composition.
AB  - The infusion therapy nurse often is in a position to intervene by assessing and
      helping to treat the nutritional status of the patients she or he serves. This
      article provides an overview of the nutritional assessment process. Tips are
      offered for estimating patient-specific nutritional needs. Basic components of
      parenteral nutrition solutions are highlighted, and general guidelines for
      initiating parenteral nutrition are included. A case study guides the reader
      through application of some principles offered in the article.

PMID- 11840005
TI  - Metabolic response and parenteral nutrition in trauma, sepsis, and burns.
AB  - Trauma, sepsis, and burns cause abnormal manifestations in the body. These
      manifestations can cause alterations in body metabolism, which complicates
      nutritional management. Goals of nutrition support with assessment modifications
      for a constantly changing population are reviewed. Patients in such stress states
      as burns, trauma, and sepsis many times need altered nutrition. This article
      outlines guidelines for total parenteral formula modification and monitoring, and
      discusses other complications such as drug interactions with parenteral formulas.

PMID- 11840008
TI  - New Products and Services.

PMID- 11840007
TI  - Glutamine supplementation. Heal the gut, help the patient.
AB  - Glutamine is the most abundant amino acid in the body. It is also one of the most
      widely researched amino acids, with multiple clinical trials on various aspects
      of medical nutritional care including gastrointestinal disease, oncology, burn
      trauma, HIV/AIDS, and chronic wound management. Glutamine often is used as a
      singular nutrient supplement in both hospital and home settings. The goal of this
      article is to review patient applications and supportive literature, and to
      provide the reader with guidelines for daily use of glutamine as an oral or
      enteral supplement.

PMID- 11840010
TI  - Comparison of two methods of instruction for the prevention of workplace
      violence.
AB  - The purpose of this study was to compare the effect of the poster session format
      (PSF) with the traditional film discussion format (FDF) on posttest scores using
      the Violence in the Workplace Knowledge Test (VWKT) for hospital staff. The 25
      item VWKT was developed by the authors. Both groups took this test as the pretest
      and posttest to determine whether there was a difference in ovrall test scores or
      a difference in score according to type of violence. The control group included a
      sample of newly hired staff (n = 51) in general hospital orientation who received
      training via the FDF method and took the posttest after the program. The
      experimental group included current staff (n = 84) who received training via the
      PSF. They "walked through" a poster session at their own pace, completing the
      posttest as they went along. The comparison of mean pretest scores on the VWKT
      for the two groups was not significantly different. However, the PSF group had
      greater improvement in test scores than the FDF group. Further analysis
      determined that the PSF group significantly improved in both types of violence
      compared to the FDF group. For this study, using an alternative teaching-learning
      strategy was more effective than the traditional method. Implications for staff
      development educators include the need to explore different methods of enhancing
      learning.

PMID- 11840011
TI  - Preventing the ax: proving education productivity and linking productivity to
      cost using the edvision methodology.
AB  - Education productivity, resource consumption, and the link between productivity
      and cost continue to be critical dimensions that need to be managed effectively
      in the face of continued downsizing and restructuring. EdVision is a fiscal based
      methodology that measures all three dimensions. The methodology was initially
      developed in the early 1990s and has been refined over the past 7 years. EdVision
      links productivity to cost by assessing Total Direct Expense per Education
      Relative Value Unit (RVU). Benchmarking this new indicator is key to moving
      toward an accurate measure of education prductivity and cost across
      organizations. EdVision allows education and training departments to prove their
      productivity and base resource decisions on data, thereby reducing vulnerability
      to unnecessary budget cuts.

PMID- 11840012
TI  - Teaching an elephant to drive. Massive staff education in a tight time frame.
AB  - Providing education and development to patient care personnel with minimal
      disruption to patient care activities is a daily challenge to staff educators.
      This article describes how a small nursing development department planned and
      coordinated the orientation to a new facility and the education and training on
      new equipment to over 1,000 nurses over a period of several months. The
      strategies used at this large, urban, academic medical center can be applied to
      other healthcare facilities.

PMID- 11840013
TI  - Nurses' retention of pain management knowledge.
AB  - Despite efforts to improve nurses' pain management knowledge, a lack of
      understanding about basic pain management concepts remains. This article presents
      results of a pilot study about the effectiveness of a pain management education
      program. Nurses' mean scores on pain management concepts tests increased from 56%
      to 76%. The scores are still low, and nurses need further education and
      reinforcement about basic pain management concepts.

PMID- 11840014
TI  - Nurses' role in patients' discharge planning at the Aga Khan University Hospital,
      Pakistan.
AB  - This descriptive cross-sectional study was designed to assess nurses' knowledge,
      perceptions, and actual practice with relation to patient discharge. Two separate
      semistructured questionnaires were used. A convenience sample of 15 nurses and 15
      patients was taken from four medical-surgical units. Fifteen patients' records
      were also studied. Analysis of the findings revealed that nurses lacked knowledge
      regarding discharge planning which also had an impact on their current discharge
      planning practices. Recommendations are provided to improve this knowledge
      deficit.

PMID- 11840015
TI  - A tribute to clinical preceptors. Developing a preceptor program for nursing
      students.
AB  - Implementing a preceptor program required the collaboration of nursing
      administrators, staff development personnel, and nursing faculty. However,
      registered nurse preceptors were the major contributors to the effectiveness of
      the program. The author developed a preceptor program for unlicensed associate
      degree nursing students and describes the experiences encountered during the
      first three semesters of the preceptor program.

PMID- 11840016
TI  - Being a staff development coordinator.

PMID- 11840018
TI  - When a GN doesn't become an RN: how the staff educator can help.
AB  - With national NCLEX pass rates declining, nursing orientation costs increasing,
      and the nursing shortage escalating, the trauma that occurs when a graduate nurse
      fails the NCLEX can be felt reverberating throughout the clinical units. NCLEX
      failure not only adversely affects the individual who fails but can have a
      profound effect on staff workload and morale. Staff educators are in a unique
      position to help the new graduate who has been unsuccessful in passing the NCLEX;
      however, they may be unsure of how to approach the situation. The authors present
      several strategies that the staff educator will find easy to implement to help
      these graduates.

PMID- 11840017
TI  - DACUM: a versatile competency-based framework for staff development.
AB  - The purpose of this article is to share a competency-based method of job analysis
      known as DACUM (Develop A CUrriculuM) that provides a credible and defensible
      framework for developing job descriptions, identifying training needs, and
      prioritizing staff development initiatives. The process capitalizes on the power
      of group synergy, interaction, and consensus and facilitates employer/employee
      buy-in. It is easily adapted for use in any occupational setting, and may be
      particularly appreciated during organizational restructuring efforts.

PMID- 11840019
TI  - Being a preceptor is stressful!
AB  - Results of a mail survey of 295 preceptors indicated preceptoring nursing
      students can be a stressful experience, with overwork identified as the main
      source of stress. Overwork resulted from unsuitability of students for the
      clinical area, lack of time, and insufficient feedback and guidance. The findings
      suggest that both students and preceptors require proper readiness assessment and
      preceptorship preparation. Preceptorship stress needs to be acknowledged; it can
      be addressed through workload adjustments and by providing feedback and support
      from nurse educators, peers, and managers.

PMID- 11840020
TI  - Using a self-learning module to teach nurses about caring for hospitalized
      children with tracheostomies.
AB  - The purpose of this study was to determine the effectiveness of using a self
      learning module (SLM) to teach nurses about caring for hospitalized children with
      tracheostomies. Data analysis using an independent samples t test showed that
      statistically significant learning occurred after completion of the SLM (p =
      0.014, n = 85). These findings can influence the way staff education is provided,
      giving the nurse educator an alternative, cost-effective, and timesaving method
      of presenting information.

PMID- 11840021
TI  - Increasing RN attendance at community-wide CE programs.
AB  - The author identifies specific chronological steps to follow when the need and
      desire is to increase RN attendance at continuing education (CE) programs. A
      brief discussion of why nurses choose not to attend CE offerings is followed by
      descriptions of topic discovery and collaboration. Important marketing principles
      and activities in using electronic, networking, postal, and media sources are
      described.

PMID- 11840022
TI  - An evolution in interdisciplinary competencies to prevent and manage patient
      violence.
AB  - Patient violence is a growing problem in healthcare institutions. Incidents of
      violence lead to injuries and increased operating costs. An innovative
      organizational approach to this problem is inclusion of interdisciplinary
      competency-based staff education and practice, as a key component of a
      comprehensive violence prevention program.Interdisciplinary competencies include
      a variety of behavioral responses, aimed at prevention, environmental,
      interpersonal, and physical interventions and postvention techniques for
      aggression and violence. Methods to maintain, monitor, document, and improve
      staff performance and skills are delineated. Organizational investment in such
      interdisciplinary competency-based education and practice evolves over time.
      Results include fewer incidents and injuries and enhanced interdisciplinary
      cooperation.

PMID- 11840023
TI  - Bringing poetry into staff development.
AB  - "Quello che mai fue detto d'alfcuna," words from Dante, "strive to say which was
      never said by anyone." This is the art of true verbal expression, the essence of
      poetry. Poet W. H. Auden once wrote that "poetry can open spaces of meaning for
      the human spirit that is more intimate to other human beings than it is to
      ourselves" (Auden, 1968). Poetry has many definitions. To some, it is the
      rhythmic verse they remember from grade school or from Mother Goose. To others,
      poetry is a verse of meter and measure, of balance and harmony. However, to most
      individuals, poetry is the ultimate expression of human emotion. Roy (1999)
      believed that nursing is in need of poetry, in order to evoke the deepest of
      images, fears, questions, and quests of the human spirit and the nursing
      profession. This article examines the use of poetry and how it might be
      incorporated into staff education.

PMID- 11840025
TI  - The Shwachman Award of the North American Society for Pediatric Gastroenterology,
      Hepatology and Nutrition, 2001: presentation.

PMID- 11840026
TI  - The Shwachman Award of the North American Society for Pediatric Gastroenterology,
      Hepatology and Nutrition, 2001: acceptance.

PMID- 11840027
TI  - The European training syllabus in pediatric gastroenterology, hepatology, and
      nutrition.

PMID- 11840028
TI  - Fundoplication: friend or foe?

PMID- 11840029
TI  - Genetics of chronic pancreatitis.

PMID- 11840030
TI  - Immune status of infants fed soy-based formulas with or without added nucleotides
      for 1 year: part 1: vaccine responses, and morbidity.
AB  - BACKGROUND: Immunologic development of soy-fed infants has not been extensively
      studied. Early studies of soy flour-based formulas showed decreased
      immunoglobulin production when soy protein intake was limited. However, there
      were no significant differences in rotavirus vaccine responses between breast-fed
      and soy protein isolate-based formula-fed infants. Nucleotides added to milk
      based formula benefit infant immune status, but reports of the immunologic
      effects of adding nucleotides to soy-based formula are not available. This study
      evaluated immune status and morbidity of infants fed soy protein isolate formulas
      with and without added nucleotides for 1 year. METHODS: Newborn, term infants
      enrolled in a masked 12-month feeding trial were assigned randomly to groups fed
      soy formula with or without added nucleotides (n = 94, n = 92). A nonrandomized
      human milk/formula cohort (n = 81) was concurrently enrolled. Recommended
      immunizations were administered at 2, 4, and 6 months. Immune status was
      determined from antibody responses to Haemophilus influenzae type b, tetanus,
      diphtheria, and poliovirus vaccines at 6, 7, and 12 months. Parents and
      physicians reported morbidity data. RESULTS: All vaccine responses were within
      normal ranges. No response differences were observed between infants fed soy
      formula and those fed nucleotide-supplemented soy. However, antibody to H.
      influenzae type b at 7 and 12 months was higher in infants fed nucleotide
      supplemented soy than in infants fed human milk/formula ( P = 0.007, P = 0.008,
      respectively). Human milk/formula-fed infants had higher poliovirus neutralizing
      antibody at 12 months than did soy-fed infants ( P = 0.016). Morbidity analyses
      showed that only physician-reported diarrhea was different among groups (groups
      fed human milk/formula had less diarrhea than did soy groups, P = 0.011).
      CONCLUSIONS: Term infants fed soy protein isolate-based formulas have normal
      immune development as measured by antibody responses to childhood immunizations.

PMID- 11840031
TI  - Immune status of infants fed soy-based formulas with or without added nucleotides
      for 1 year: part 2: immune cell populations.
AB  - BACKGROUND: Infants fed a soy protein isolate-based formula have immunization
      responses similar to breast-fed infants. However, cellular aspects of the
      immunologic development of soy-fed infants have not been studied extensively.
      Nucleotides added to milk-based formula benefit infant immune status, but reports
      of the immunologic effects of adding nucleotides to soy-based formula are not
      available. This study examines immune cell populations of infants fed soy protein
      isolate formulas with and without added nucleotides for 1 year. METHODS: Newborn,
      term infants studied in a masked 12-month feeding trial were assigned randomly to
      soy formula groups with and without added nucleotides (n = 94, n = 92). A
      nonrandomized human milk/formula-fed cohort (n = 81), was concurrently enrolled.
      Blood samples were collected at 6, 7, and 12 months. Thirty-two immune cell
      populations were characterized using three-color flow cytometry. Cellular markers
      were chosen to assess general pediatric immune status, emphasizing maturation and
      activation of B, T, and NK lymphocytes. RESULTS: All cell populations, number and
      percentages, were within age-related normal ranges. The only significant
      difference found between soy formula and human milk/formula-fed infants was the
      percentage of CD57 + NK T cells at 12 months (human milk/formula > soy formula, P
      = 0.034). There were significant differences at some time points between human
      milk/formula-fed and nucleotide-supplemented soy formula-fed infants in
      populations of lymphocytes, eosinophils, total T, helper T, naive helper,
      memory/effector helper, CD57 - T, and CD11b + CD8 + NK cells. None of the cell
      populations differed between infants fed soy formula versus soy plus nucleotides.
      CONCLUSIONS: Infants fed this commercial soy formula demonstrated immune cell
      status similar to human milk/formula-fed infants, consistent with normal immune
      system development. The addition of nucleotides to soy formula did not
      significantly change specific individual immune cell populations but tended to
      increase numbers and percentages of T cells and decreased numbers and percentages
      of NK cells.

PMID- 11840032
TI  - Ganciclovir treatment in infants with cytomegalovirus infection and cholestasis.
AB  - BACKGROUND: The authors have previously described an association between
      cytomegalovirus (CMV) infection and intrahepatic and extrahepatic forms of
      neonatal cholestasis. Pediatric use of the antiviral drug ganciclovir to treat
      patients with CMV infection has increased. In this study, infants with CMV
      infection and cholestasis were treated with ganciclovir. METHODS: Six infants
      with cholestasis (age, 3-16 weeks) and with signs of ongoing CMV infection were
      treated with intravenous ganciclovir for 3 to 7 weeks and observed for 4 to 31
      months after treatment. Two patients had biliary atresia, one had suspected septo
      optic dysplasia and three had no obvious cause for intrahepatic cholestasis other
      than ongoing CMV infection. RESULTS: Four patients, including one with biliary
      atresia, responded to the treatment, whereas two patients, including the one with
      septo-optic dysplasia did not. The latter patient had episodes of symptomatic
      hypoglycemia during the treatment, which was subsequently stopped. Liver function
      at the end of follow-up was good in four patients, intermediate in one, and poor
      in one. CONCLUSION: Ganciclovir treatment may be beneficial in infants with CMV
      associated intrahepatic cholestasis, but controlled studies are needed. Because
      of the possible side effect of hypoglycemia, infants with cholestasis who have
      increased risk for such episodes should not be treated.

PMID- 11840033
TI  - Modeling 13C breath curves to determine site and extent of starch digestion and
      fermentation in infants.
AB  - BACKGROUND: The colon salvages energy from starch, especially when the capacity
      of the small intestine to digest it is limited. The aim of this study was to
      determine the site and relative extent of starch digestion and fermentation in
      infants. METHODS: Thirteen infants (10 male and 3 female infants), median age
      11.8 months (range, 7.6-22.7 months), were fed a starchy breakfast containing 13C
      labeled wheat flour after an overnight fast. Duplicate breath samples were
      obtained before breakfast and every 30 minutes for 12 hours. Breath 13CO2
      enrichment was measured using isotope ratio mass spectrometry, and results were
      expressed as percentage dose recovered (PDR) for each 30 minutes. The PDR data
      were analyzed and mathematically modeled assuming either a constant estimate of
      CO2 production rate or adjusted for physical activity. RESULTS: Mean +/- SD
      cumulative 13C PDR (cPDR) at 12 hours was 21.3% +/- 8.4% for unadjusted data and
      26.5% +/- 11.6% for adjusted data. A composite model of two curves fit
      significantly better than a single curve. Modeling allowed estimation of cPDRs of
      small intestine (17.5% +/- 6.5% and 22.7% +/- 9.3% for unadjusted and adjusted
      data, respectively) and colon (4.6% +/- 2.9% and 6.3% +/- 5.4%). CONCLUSIONS:
      Modeling of 13CO2 enrichment curves after ingestion of 13C-enriched wheat flour
      is an attractive means to estimate the contribution of the upper and lower gut to
      starch digestion and fermentation.

PMID- 11840034
TI  - Does ileal reverse segment in rats with short bowel syndrome change intestinal
      morphology?
AB  - BACKGROUND: The primary goal of surgical therapy for short bowel syndrome is to
      increase intestinal absorptive capacity. Many surgical procedures have been
      described for this purpose. One of these is ileal reverse-segment procedure. This
      procedure after massive small-bowel resection is an alternative way to treat
      short bowel syndrome, but how it affects intestinal morphology in short bowel
      syndrome has not been investigated. The aim of this study is to investigate
      macroscopic and microscopic effects of reverse-segment procedure on the short
      bowel. METHODS: Twenty rats underwent resection of 80% of the small bowel. The
      rats were separated into two groups (n = 10). In the first group (reverse group),
      a reverse segment was formed by twisting a 2-cm ileal segment 180 degrees,
      without damaging its vascularity. In the second group (control group), a 2-cm
      ileal segment was resected, preserving its mesentery, and end-to-end anastomosis
      was performed to maintain the intestinal passage. The segment was not twisted 180
      degrees. The 2-cm proximal (jejunal) and distal (ileal) segments of the resected
      bowel were reserved for histologic investigation. Two months later, the rats were
      killed and the jejunal and ileal segments were evaluated morphologically.
      RESULTS: In the reverse group, body weight and total intestinal length
      significantly increased (14% more than in the control group). The diameter of
      both proximal (jejunal) and distal (ileal) segments in the reverse group also
      increased 53.8% and 22.8%, respectively ( P < 0.05). Histologically, crypt depth
      and villus height of the ileal segment in the reverse group increased 15.2% and
      18.2% more than in the control group ( P < 0.05). No histologic change was
      observed at the jejunal level except for intestinal muscle thickness.
      CONCLUSIONS: Ileal reverse-segment procedure in rats with short bowel syndrome 1)
      does not cause intestinal obstruction, 2) increases total bowel length and body
      weight, 3) increases the diameter of both jejunal and ileal segments, and 4)
      increases villus height and crypt depth only at the ileal level. For this reason,
      reverse-segment procedure positively affects intestinal adaptation.

PMID- 11840035
TI  - Developmental changes in cyclooxygenase mRNA expression in the gastric mucosa of
      rats.
AB  - BACKGROUND: In newborn rats, gastric mucosa is more susceptible to various
      damaging agents and recovers from injury more quickly than in older animals. To
      determine whether metabolism of prostaglandins is responsible for this mucosal
      protective mechanism in developing rats, we studied cyclooxygenase (COX) mRNA
      expression in the mucosa using quantitative real-time polymerase chain reaction
      (PRC). METHODS: Cyclooxygenase-1 and COX-2 mRNA was extracted from the gastric
      mucosa of rats of various ages and quantitatively analyzed using real-time PCR
      with dual-labeled fluorogenic probes. The copy numbers of cDNA for COX-1 and COX
      2 were standardized to glyceraldehyde-3-phosphate dehydrogenase from the same
      sample. RESULTS: Cyclooxygenase-1 mRNA expression was lowest in 1-week-old rats
      and highest in 4-week-old rats. Mucosal damage produced by 150 mmol/L HCl and 60%
      ethyl alcohol did not increase COX-1 mRNA expression in any age group.
      Cyclooxygenase-2 mRNA expression increased significantly with age. Mucosal injury
      increased COX-2 mRNA in each age group, especially in 1-week-old rats.
      Intraperitoneal lipopolysaccharide also increased COX-2 mRNA in both 1- and 4
      week old rats. CONCLUSION: The high level of COX-2 mRNA expression in the gastric
      mucosa of 1-week-old rats may be responsible for the physiologic characteristics
      of gastric mucosal defenses in this age group.

PMID- 11840036
TI  - Increased parenteral amino acid administration to extremely low-birth-weight
      infants during early postnatal life.
AB  - BACKGROUND: Early administration of parenteral amino acids to infants with
      extremely low birth weight (birth weight < or = 1,000 g) has been encouraged to
      foster growth. However, excessive intravenous intake of amino acids may cause
      metabolic acidosis and uremia in extremely low birth weight infants. The
      hypothesis for this study was that extremely low birth weight infants would
      tolerate slightly increased early postnatal parenteral amino acid administration
      and benefit. METHODS: The peak daily parenteral amino acid dosage was increased
      from 3 g/kg (standard group) to 4 g/kg (modified group). The corrected parenteral
      amino acid dosage was computed to account for enteral protein intake and keep the
      combined daily intravenous amino acid and enteral protein intake at or below 3 g
      . kg -1 . d -1 in the standard group and 4 g . kg -1 . d -1 in the modified
      group. The primary outcome measure was plasma bicarbonate concentration as an
      indicator of acid-base status. Data were collected for patient demographics,
      nutritional intake, serum bicarbonate and serum urea nitrogen concentrations, and
      outcome. RESULTS: The corrected parenteral amino acid intake of the modified
      group was 16% greater at postnatal week 1 (3.30 +/- 0.83 g . kg -1 . d -1; mean,
      +/-1 SD) and 18% greater (3.86 +/- 0.94 g . kg -1 . d -1 ) at postnatal week 2
      than the parenteral amino acid intake of the standard group. In the modified
      group, the mean serum bicarbonate concentration was 19.1 +/- 1.8 mEq/dL at week 1
      and 23.9 +/- 2.9 mEq/dL at week 2, with no difference between the groups. At week
      1, serum urea nitrogen concentrations were the same in both groups. The mean
      serum urea nitrogen concentration of the modified group at postnatal week 2 (18.2
      +/- 8.8 mg/dL) was unchanged from postnatal week 1, but was greater than that of
      the standard group at postnatal week 2. Weight gain was the same in both groups.
      Corrected parenteral amino acid intake at postnatal week 1 correlated directly
      with weight gain from birth to postnatal week 2 ( P < 0.03) in both groups.
      CONCLUSIONS: Infants with extremely low birth weight tolerated parenteral amino
      acid intake of approximately 4 g . kg -1 . d -1. Mild increases of mean serum
      urea nitrogen concentration and mean weight gain were associated with increased
      parenteral amino acid administration without significant acidosis.

PMID- 11840038
TI  - Antibacterial characteristics in the feces of breast-fed and formula-fed infants
      during the first year of life.
AB  - BACKGROUND: Human milk is known to protect infants from a number of infectious
      diseases. Much less is known about the bioactivity of milk-derived factors in the
      intestine. In this study, potentially protective characteristics in the feces of
      breast-fed and formula-fed infants were compared. METHODS: The feces of 26 breast
      fed and 18 formula-fed infants were collected during the first year of life. In
      each sample, the concentrations of total protein, immunoglobulin A, and sialic
      acid were measured. In addition, the effect of the fecal samples was measured on
      the adhesion of enteropathogenic Escherichia coli (EPEC) to Caco-2 cells and on
      transepithelial electrical resistance (TER) during an infection. RESULTS: In the
      first month, sialic acid and immunoglobulin A were found in the feces of breast
      fed infants in substantially higher concentrations than in the feces of formula
      fed infants (sialic acid, 1197 +/- 370 microg/ mL versus 31 +/- 19 microg/ mL;
      immunoglobulin A, 0.11 +/- 7 mg/mL versus 0.3 +/- 1 mg/mL) and thereafter
      decreased to similar levels in half a year. Adhesion of EPEC to Caco-2 cells was
      inhibited between 65% and 85% by stools from both groups. The decrease of TER
      during EPEC infection was unaffected by fecal samples of any origin or age.
      CONCLUSION: Potentially protective factors are present in higher concentrations
      in the stools of breast-fed infants than in stools of formula-fed infants.
      Interestingly, feces from breast-fed and formula-fed infants inhibited bacterial
      adhesion to a similar level, but neither was able to preserve epithelial barrier
      function.

PMID- 11840037
TI  - Diet-related adaptation of the small intestine at weaning in pigs is functional
      rather than structural.
AB  - BACKGROUND: Incidence of diarrhea at weaning in commercial pigs is an important
      problem, and diet is thought to be a predisposing factor. The aim of this study
      was to determine the impact of switching from milk-based to cereal-based diets on
      the morphology and function of the small intestine of piglets using a model of
      delayed weaning to isolate the influence of the diet from that of environmental
      and social factors. METHODS: Forty-five piglets received a milk-based diet for 5
      weeks after weaning. Thirty piglets were then switched from milk-based to wheat-
      or barley-based diets, mimicking the dietary change that occurs at weaning. The
      last 15 piglets remained on the milk-based diet. Piglets were killed 4 days after
      the dietary switch. Jejunal mucosa morphometry and enzyme activities were
      measured. Ussing chambers were used to measure intestinal permeability to
      macromolecules, basal electrical properties, glucose absorption, and induced
      chloride-secretion. RESULTS: Alkaline phosphatase- and sucrase-specific
      activities were higher in both groups of cereal-fed piglets than in milk-fed
      piglets. Dipeptidylpeptidase IV activity was higher in wheat-fed piglets than in
      the other groups. Na + -dependent glucose absorption was 1.7-fold higher in
      cereals-fed piglets than in milk-fed piglets. Serotonin-induced and vasoactive
      intestinal polypeptide-induced chloride secretion was doubled in cereals-fed
      piglets. Dietary transition did not influence the other parameters. CONCLUSIONS:
      These results indicate that switching from milk to cereals increased some mucosal
      enzyme activities, intestinal Na + -dependent glucose absorption, and response to
      secretagogues. This supports the hypothesis that dietary factors could initiate
      diarrhea in the presence of other aggravating factors, such as pathogens or
      environmental stress.

PMID- 11840039
TI  - Omeprozole therapy in pediatric patients after liver and intestinal
      transplantation.
AB  - BACKGROUND: Proton pump inhibitors such as omeprazole are increasingly used to
      prevent stress-related gastric bleeding in critically ill patients. In this
      investigation, the acid-suppressive potency of omeprazole was assessed in one at
      risk group, pediatric patients undergoing liver or intestinal transplantation, or
      both. METHODS: Twenty-two patients ranging in age from 0.9 to 108 months (23.8 +/
      6.5) underwent isolated liver (n = 10) or intestinal (11 with composite liver
      allografts) transplantation. Omeprazole was delivered in bicarbonate suspension
      through a nasogastric tube. Therapy was started after surgery at 0.5 mg/kg every
      12 hours. Gastric pH monitoring was performed approximately 2 days later.
      RESULTS: For the entire group, mean gastric pH equaled 6.1 +/- 0.3, the same in
      recipients of isolated liver and intestinal allografts. Twelve of the 22 patients
      demonstrated a discontinuous omeprazole effect, that is, dissipation of acid
      reduction before the next dose. Five of the 12 patients with discontinuous
      omeprazole effect had mean gastric pH of less than 5 (3.9 +/- 0.4). In 4 of these
      5, the omeprazole dosing interval was shortened to every 8 or every 6 hours,
      resulting in an increase in mean pH to 6.6 +/- 0.2 ( P < 0.01). In the remaining
      10 of 22 patients, acid suppression was uninterrupted until the next dose. No
      patient experienced bleeding attributable to gastric erosion. CONCLUSION:
      Omeprazole suspended in sodium bicarbonate is an effective acid-suppressing agent
      in pediatric recipients of liver or intestinal transplant, or both. A dosage of
      0.5 mg/kg every 12 hours is sufficient for most patients, but dosing every 6 to 8
      hours is required to assure maximal acid suppression in all.

PMID- 11840040
TI  - Does interferon and ribavirin combination therapy increase the rate of treatment
      response in children with hepatitis C?
AB  - BACKGROUND: Interferon-alpha was the first accepted treatment of chronic
      hepatitis C. In recent years, adding ribavirin has produced better response rates
      in adult patients than monotherapy with interferon-alpha. Whether adding
      ribavirin also improves treatment results in pediatric patients remains unclear.
      METHODS: Twelve patients were given 3 million U/m 2 subcutaneous interferon-alpha
      three times weekly and 15 mg/kg oral ribavirin daily, and 10 patients were given
      only 3 million U/m 2 subcutaneous interferon-alpha three times weekly for a total
      of 12 months. RESULTS: The dropout rate was 22.8% (25% for patients receiving
      combination treatment versus 20% for those receiving monotherapy). At the end of
      treatment, viral clearance was achieved in 50% of the patients who received
      combination treatment versus 30% of those who received monotherapy. After 12
      months of posttreatment follow-up, sustained response rates were 30% and 41.7%,
      respectively. Of those who responded to treatment, 66.7% had received ribavirin
      whereas 37.5% of nonresponders had received ribavirin therapy. CONCLUSION: Adding
      ribavirin to interferon treatment improved end-of-treatment response rates in
      children with chronic hepatitis C. Tolerance of treatment was similar to
      tolerance of monotherapy. However, studies of greater numbers of pediatric
      patients with longer follow-up periods are necessary to determine prolonged
      sustained response.

PMID- 11840041
TI  - A prospective study of endoscopic esophageal variceal ligation using a multiband
      ligator.
AB  - BACKGROUND: Endoscopic variceal band ligation (EVL) is the preferred method of
      treating variceal hemorrhage in adults. The need to reinsert the endoscope after
      reloading for each varix ligation has been a drawback. The Saeed multiband
      ligator allows ligation of multiple varices during a single insertion. The
      multibander has not been used previously in children. METHODS: Twenty-eight
      consecutive children were referred to a pediatric liver unit because of
      esophageal variceal bleeding from 1998 to 2000. Endoscopic variceal band ligation
      was performed at initial endoscopy and repeated monthly until varices were
      obliterated or were too small to ligate. RESULTS: Results are expressed as median
      (range). Age at EVL was 11 years (3 months to 16 years) and weight 30 kg (5.4-63
      kg). Portal hypertension was caused by cirrhosis in 15 children. Endoscopic
      variceal band ligation was performed on 66 occasions with 4 bands applied per
      session. Ten children had active bleeding at initial endoscopy and all responded
      to EVL. Interval bleeding developed in 2 children before variceal ablation.
      Varices were obliterated in 26 of 28 patients after 2 sessions. During the 21
      month follow-up (2 months to 3 years), six children have undergone elective liver
      transplantation and three have had mesoportal bypass procedures. Rebleeding
      developed in 2 of 26; 1 from recurrent esophageal varices that responded to
      repeat EVL and 1 from gastric varices. Following variceal ablation, 2-year
      actuarial variceal recurrence risk was 40%. CONCLUSIONS: Endoscopic variceal
      ligation is highly effective in obliterating esophageal varices in children. The
      use of a multibander device for endoscopic variceal ligation is technically
      feasible and safe even in small children, and its use results in more rapid
      ablation of esophageal varices.

PMID- 11840042
TI  - Atypical morphologic presentation of biliary atresia and value of serial liver
      biopsies.
AB  - BACKGROUND: Liver biopsy findings are important in diagnosing extrahepatic
      biliary atresia. Diffuse ductular proliferation is a characteristic finding. We
      describe four patients with conjugated hyperbilirubinemia in whom the initial
      liver biopsy findings showed a lack of ductular proliferation, despite subsequent
      development of biliary atresia. RESULTS: On initial biopsy, paucity of
      intrahepatic bile ducts was present in three of four patients, with a bile duct
      to portal space ratio of 0.3 to 0.4 (normal, 0.9-1.8). A normal bile duct to
      portal space ratio of 1.0 was observed in the fourth patient. Ductular
      proliferation became apparent in three subjects between 9 and 12 weeks of age,
      and biliary atresia was noted at the time of a Kasai portoenterostomy. The fourth
      child had well-developed biliary cirrhosis at liver transplantation. CONCLUSIONS:
      Changes characteristic of biliary atresia may appear even after 9 weeks of age.
      Bile duct paucity and normal bile duct to portal space ratio do not preclude the
      subsequent development of biliary atresia. Infants with unexplained conjugated
      hyperbilirubinemia and acholic stools should undergo sequential liver biopsies
      until clinical improvement occurs or until biliary atresia can be excluded from
      the differential diagnosis.

PMID- 11840043
TI  - Crohn disease in an adolescent with galactosemia.

PMID- 11840044
TI  - Shwachman syndrome in a preterm newborn associated with transient diabetes
      mellitus.

PMID- 11840045
TI  - Severe antibiotic-associated colitis in a patient with cystic fibrosis and
      colonic wall thickening.

PMID- 11840046
TI  - Salivary transmission in an intrafamilial cluster of hepatitis B.

PMID- 11840047
TI  - Pathophysiology of hypoganglionosis.

PMID- 11840048
TI  - Fibrosis: a general feature in cystic fibrosis?

PMID- 11840050
TI  - Minimally invasive surgery on full-thickness intestinal biopsies.

PMID- 11840049
TI  - First study on the prevalence of celiac disease in a Portuguese population.

PMID- 11840051
TI  - New approaches in case management.

PMID- 11840052
TI  - Southeast Michigan Diabetes Outreach Network: quality improvement project for
      diabetes care.
AB  - This article describes the development and process measures with related outcomes
      of the Southeast Michigan Diabetes Outreach Network (SEMDON), one of six Diabetes
      Outreach Networks in Michigan. SEMDON's mission is to strengthen diabetes
      prevention, detection, and treatment. Education in diabetes management is
      provided to participating agencies. The agency staff collect baseline data on
      patients with diabetes including demographics and physiologic measures. Education
      is given to the patients by the staff nurses. The collection of information on
      several care process measures and intermediate outcomes is repeated at 6 months.
      A report of matched data of these agencies from 404 individuals with diabetes is
      presented. The outcomes of blood glucose, hemoglobin A1c, blood pressure, and
      annual foot and eye exams will be analyzed. The SEMDON model may be an effective
      approach in improving the quality of diabetes care.

PMID- 11840053
TI  - Customizing a relational database to support a clinical case management program.

PMID- 11840054
TI  - The influence of telephonic nursing care coordination on patient satisfaction in
      a predominantly low-income, high-risk pregnancy population.
AB  - The effect of telephonic nursing case management on patient satisfaction in a
      predominantly non-Caucasian low-income, high-risk pregnancy population was
      studied. Patient satisfaction of care was significantly higher for treatment
      group participants than for controls on 9 of 10 items measuring satisfaction. The
      satisfaction score of the treatment patients, constructed by summing scores for
      each item, averaged 8 points higher than the control group's score. Demographics
      made little difference. Telephonic case management was the strongest predictor of
      satisfaction in a multiple regression analysis. Satisfaction was unrelated to
      mode of delivery, infant birth weight, or gestational age. The satisfaction
      levels of treatment patients were high, whether or not they had outpatient
      charges. Participants rated the program highly for the nurses' ability to answer
      questions, overall program experience, the opportunity to ask the nurses
      questions, health teachings and instructions received, and confidence in the
      nurse coordinating their care or their child's care.

PMID- 11840055
TI  - Evaluation of critically ill patients for transfer to long-term acute-care
      facilities.

PMID- 11840056
TI  - Strategy management system in perinatal services: the role of a patient resource
      manager.
AB  - The purpose of this article is to illustrate the role of a patient resource
      manager in an academic healthcare organization which has implemented a strategy
      management system. This management system is composed of communication tools
      organized in a balanced scorecard to support/promote ongoing growth and
      development using Kaplan and Norton's Strategy Management System. The historical
      development of Duke University Health System (DUHS) is presented articulating the
      mission, vision, and strategic agenda of the DUHS with the Clinical Service Unit
      initiative and its relevance to Women's Services. Kaplan and Norton's 5 core
      principles of the strategy management system are applied to Women's Services with
      implementation and evaluation of the patient resource manager role. Moreover,
      outcomes are discussed using the Balanced Scorecard. Lastly, implications and
      recommendations for replication of this system are summarized for ongoing
      development in this continuous learning organization.

PMID- 11840058
TI  - Are you an empowered person?

PMID- 11840057
TI  - Are there legal issues of concern for nurses when patients use complimentary and
      alternative medicine?

PMID- 11840059
TI  - Don't Forget Informatics When Thinking About Patient Safety.

PMID- 11840060
TI  - Progress: Editor's Web Site and More.

PMID- 11840061
TI  - Creating a research partnership: graduate nursing students and clinical nurses.

PMID- 11840062
TI  - Reaction to disaster volunteering not what I expected.

PMID- 11840063
TI  - Cheating must be okay--everybody does it!
AB  - Cheating has been a part of structured academics since time immemorial. Students
      cheat to pass a test, to pass a course, and to get better grades than others.
      They also cheat to obtain the benefits that better grades offer-scholarships,
      admission to graduate programs, recognition at ceremonies, and prestigious job
      offers. This article presents data obtained from a survey of nursing students and
      lists the measures taken to reduce cheating in the classroom.

PMID- 11840064
TI  - Comprehensive performance review: preparing students for a preceptor experience.

PMID- 11840065
TI  - Incorporating faith-based partnerships into the curriculum.

PMID- 11840067
TI  - Considering theory in assessing quality of web-based courses.
AB  - There are significant implications to jumping on the Internet-course bandwagon,
      and several questions should be answered before offering or enrolling in such a
      course. This article provides information on how quality has been assessed with
      online education, reviews the theoretical framework used in conducting such
      research, and provides a recommendation on which theory is most promising in
      evaluating the quality of Internet courses.

PMID- 11840066
TI  - Students' perceptions of variables influencing retention: a pretest and post-test
      approach.

PMID- 11840068
TI  - Aesthetic knowing: understanding the experience of chronic illness.
AB  - Aesthetic knowing can help students gain a deeper understanding of a client's
      life with chronic illness. Simply asking clients to describe what their illness
      means is not enough. Having clients express themselves through a form such as a
      drawing, poetry, song, pictures, letters, or any form comfortable to the clients
      often reveals critical information that can change the direction of planned
      nursing care. This article presents the process and outcomes of asking nursing
      students to do an aesthetic project with one of their clients whose case they
      managed in the community during the semester.

PMID- 11840069
TI  - International clinical experiences: long-term impact on students.
AB  - The realization that international learning experiences can provide an excellent
      opportunity for nursing students to practice nursing in a cultural system
      different from their own, gain an increased global perspective, and enhance their
      cultural competency, has led to the development of international nursing
      education programs across the globe. The authors explore the long-term impact on
      students of such an experience in Nicaragua. Graduates report how their
      knowledge, personal growth, and interpersonal connections were influenced by the
      experience

PMID- 11840070
TI  - Assessing nurse graduate leadership outcomes: the "typical day" format.
AB  - Readiness for professional nursing practice in the current diverse and complex
      healthcare environment requires leadership capabilities. Faculty are challenged
      to identify specific leadership capabilities needed by graduate nurses upon entry
      into professional practice and to develop models from which they can accurately
      and authentically assess their demonstration. This article presents the
      development and implementation of an innovative leadership outcome assessment
      model. The model was developed in collaboration with nurse practice leaders and
      uses nurse practice leaders as external assessors and a "typical day" in nursing
      practice format.

PMID- 11840071
TI  - The mentored journal.
AB  - The "writing to learn" paradigm assists students in developing reflection,
      critical thinking, and the higher order cognitive skills of analysis and
      synthesis. One common teaching strategy used in this process is clinical
      journals. Integrating the concepts and underlying theory of journaling,
      mentoring, and the Circles of Meaning model in the development of the mentored
      journal, the author discusses a model in which each component acts
      synergistically to enhance the process of critical thinking within nursing
      students.

PMID- 11840072
TI  - Negligence in nursing education.
AB  - Nursing faculty members should be aware that they are at risk for litigation if
      found negligent in failing to protect students from injury. Although student
      contributory negligence and willing assumption of risk are frequent defenses
      against negligence, the courts have determined that educators have a
      responsibility to determine foreseeable risks and to instruct students on how to
      maintain safety. The purpose of this article is to describe legal cases involving
      negligence in education and to discuss ways educators can reduce the risk of
      injury to students and potential litigation charging educational negligence

PMID- 11840073
TI  - Treatment of childhood tuberculosis with a six month directly observed regimen of
      only two weeks of daily therapy.
AB  - BACKGROUND: Recommended treatment of childhood tuberculosis is 6 months in
      duration with at least 3 drugs. We studied a regimen requiring as few as 58
      doses, given entirely by directly observed therapy (DOT), under program
      conditions. METHODS: An observational trial was conducted to determine the
      effectiveness of a completely DOT 6-month regimen for pulmonary, pleural and
      lymph node tuberculosis in children with the use of 2 weeks of daily isoniazid,
      rifampin and pyrazinamide therapy; then 6 weeks of twice weekly isoniazid,
      rifampin and pyrazinamide therapy; followed by 16 weeks of twice weekly isoniazid
      and rifampin. All therapy was given by workers from the health department, and
      patients were followed by the Children's Tuberculosis Clinic in Houston, TX.
      Patients were evaluated for changes in symptoms, weight, clinical or radiographic
      findings and adherence to therapy. RESULTS: Of the 175 evaluable children (159
      pulmonary/thoracic node, 4 pleural, 12 cervical lymph node), 81% of children
      completed treatment in 6 months. Of the 33 patients who received extended
      treatment, 3 did so because of physician choice, 17 had an inadequate response to
      initial therapy, 2 had significant adverse reactions to drugs and 16 had poor
      adherence to the DOT. Only 37% of patients had complete resolution of disease at
      the end of treatment, but all continued to improve after therapy was stopped.
      There was only 1 patient who relapsed after 4 years. CONCLUSION: This regimen had
      results comparable with those of 6-month regimens with longer durations of daily
      therapy. Determining treatment response in pediatric tuberculosis is difficult
      because of the slow resolution of chest radiograph abnormalities. DOT is an
      important aspect of treatment but does not solve all problems with treatment
      adherence.

PMID- 11840074
TI  - Lack of association between rotavirus infection and intussusception: implications
      for use of attenuated rotavirus vaccines.
AB  - BACKGROUND: Withdrawal of the tetravalent rhesus-human rotavirus vaccine
      Rotashield because of its association with intussusception raised concerns about
      a potential link between natural rotavirus disease and intussusception. Our
      objective was to determine whether such an association exists. METHODS: In the
      Southern California Kaiser Permanente Health Care Plan, a large health
      maintenance organization, from October, 1992, to July, 1999, we retrospectively
      identified by computerized data and medical charts all children <3 years old with
      intussusception, and from 1997 to 1999 we independently identified by prospective
      clinical and laboratory evaluation children <3 years old with rotavirus diarrhea.
      We compared the epidemiologic characteristics of intussusception and rotavirus
      infection in our study population and evaluated for the presence of both diseases
      in individual patients. RESULTS: Using computerized data we identified 124 cases
      of intussusception, 101 (81%) of which were confirmed by medical chart and
      radiologic reviews. The incidences for infants <1 year old and for children <3
      years old were 41 (95% confidence interval, 32 to 55) and 17 (95% confidence
      interval, 13 to 20) per 100,000 child years, respectively. Between November 1997
      and July 1999, we identified 470 cases of rotavirus diarrhea and none had
      intussusception. Although rotavirus diarrhea had a distinct peak incidence
      between December and February, intussusception had no apparent seasonality. The
      age distributions overlapped, but intussusception occurred at an earlier age than
      rotavirus disease. CONCLUSIONS: We found no epidemiologic evidence for an
      association between intussusception and natural rotavirus infection, but our
      study was limited by an insufficient number of cases to definitively exclude a
      causal link. The dramatic winter peak of rotavirus disease had no discernable
      parallel in the incidence of intussusception. Our data suggest that the
      association between tetravalent rhesus-human rotavirus vaccine and
      intussusception may possibly result from the nonhuman rotavirus components of
      that vaccine.

PMID- 11840075
TI  - Epidemiologic picture of Kawasaki disease in Beijing from 1995 through 1999.
AB  - OBJECTIVE: Kawasaki disease (KD) is supposed to be more common in the Asian race.
      The incidence in Japan is 10-fold higher than rates reported from western
      countries. This study sought to evaluate the epidemiologic picture of KD in
      Beijing and its suburbs. METHOD: A questionnaire form and diagnostic guidelines
      for KD were sent to all hospitals with pediatric inpatient beds throughout
      Beijing and its suburbs. Pediatricians were asked to review the medical records
      and report all patients with KD diagnosed during the 5-year period from January,
      1995, through December, 1999. RESULTS: A total of 710 patients with KD were
      reported from 37 (95%) of 39 hospitals with pediatric inpatient beds. The
      incidences of KD for each year of the study were 18.2 (1995), 21.1 (1996), 18.6
      (1997), 30.6 (1998) and 27.8 (1999) per 100,000 children <5 years of age. The
      male:female ratio was 1.7:1. The age at onset ranged from 1 month to 13.4 years
      (median, 2.3 years), with 85.2% <5 years old. The disease occurred more
      frequently in spring and summer and less frequently in autumn and early winter.
      Lymph node enlargement was the least common clinical sign, and its incidence
      decreased from 1995 to 1999. Cardiac abnormalities were found in 21.5% of
      patients and were more prevalent in patients diagnosed 10 days or longer after
      the onset. No patients died in the acute stage. CONCLUSION: The incidence of KD
      in Beijing is lower than that reported in Japan, similar to the incidence in the
      United States and higher than in other western countries. The age and gender
      distribution and increasing trend in incidence are similar to those in previous
      reports, but seasonal distribution is unique.

PMID- 11840076
TI  - Evaluation of children with recurrent pneumonia diagnosed by World Health
      Organization criteria.
AB  - BACKGROUND: A World Health Organization (WHO) case management approach has been
      used to identify and treat children with pneumonia worldwide since 1987. Many
      children are treated repeatedly: 23% of children with pneumonia in our rural
      Haitian district had met the WHO criteria on two or more occasions; but
      underlying disease in such children has not been systematically studied. METHODS:
      We enrolled 103 children who had been diagnosed with pneumonia on 3 or more
      occasions by community health workers using WHO criteria. We compared them with
      138 children similarly evaluated but never diagnosed with pneumonia, matching by
      health worker and age. We administered questionnaires to parents and performed
      complete physical examinations, tuberculin skin tests and serologic testing for
      HIV on all subjects and chest radiographs on case children. RESULTS: Two percent
      of case children and 1.5% of controls had positive tuberculin skin test
      reactions. None of the children tested was HIV-seropositive. Ninety-four case
      children had normal baseline chest radiographs and three had focal infiltrates. A
      history of wheezing was reported for 79% of case children and 61% of controls (P
      = 0.002), and wheezing with exercise was reported for 36% and 22%, respectively
      (P = 0.02). DISCUSSION: Most children in Haiti with recurrent pneumonia diagnosed
      by WHO criteria do not have evidence of tuberculosis, HIV infection or pulmonary
      anomalies, but they may be more likely to have asthma, and this should be
      considered as an alternative diagnosis. This information should help direct
      evaluation of such children in other settings and prompt further study of asthma
      in developing countries.

PMID- 11840077
TI  - No evidence for short or long term morbidity after increased titer measles
      vaccination in Sudan.
AB  - BACKGROUND: Increased mortality rates have been reported after high titer measles
      [>10(5.0) plaque-forming units (PFU)] vaccination in several large studies in the
      developing world. An increased titer measles vaccine study conducted in Sudan
      included a prolonged prospective evaluation of childhood morbidity after
      vaccination. METHODS: Five hundred ten children (170 per group) were randomized
      to receive 1 of 3 regimens at 5 and 9 months of age: (1) meningococcal vaccine,
      then standard titer (50% tissue culture-infective dose, 103.8) Schwarz measles
      vaccine; (2) increased titer (10(4.7) PFU) Edmonston-Zagreb measles vaccine
      followed by meningococcal vaccine; and (3) increased titer (10(4.7) PFU)
      Connaught vaccine followed by standard titer Schwarz measles vaccine. RESULTS:
      Health workers collected information at 31,582 semi-monthly and monthly visits
      during 5 years. No increase in infant mortality was observed, but the statistical
      power was limited. There were 13, 13 and 10 deaths in the Schwarz, Edmonston
      Zagreb and Connaught groups, respectively. There were no differences in duration
      or incidence of illness between groups at any time during the 5-year follow-up,
      with comparisons stratified by age and sex. Statistical power for each pairwise
      comparison was good, with at least 80% power to detect a difference of 1 day per
      month of illness and a 12% difference in the proportion of visits with an illness
      recorded. CONCLUSIONS: We were unable to document increased morbidity in
      recipients of the increased titer measles vaccines used in this study. These data
      do not support the hypothesis that increased mortality after increased titer
      vaccine exposure is the result of increased and cumulative morbidity.

PMID- 11840078
TI  - Stavudine, nevirapine and ritonavir in stable antiretroviral therapy-experienced
      children with human immunodeficiency virus infection.
AB  - BACKGROUND: The efficacy and tolerance of switching from zidovudine (ZDV) and
      lamivudine (3TC) in clinically stable HIV-infected children with incomplete viral
      suppression to stavudine (d4T), nevirapine (NVP) and ritonavir (RTV) has not been
      determined. Aim. To evaluate the safety, tolerance, antiviral activity and
      immunologic changes after the change to a three drug combination. METHODS: During
      a clinical trial in which HIV-infected antiretroviral-experienced children were
      initially randomized to receive d4T/RTV, ZDV/3TC/RTV or ZDV/3TC (Step 1), 48
      children who had HIV RNA > or = 10,000 copies/ml after > or = 12 weeks of ZDV/3TC
      therapy in Step 1 were switched to d4T/NVP/RTV in Step 2. The proportion of
      children receiving therapy with HIV RNA < or = 400 copies/ml at Study Weeks 24
      and 48 receiving d4T/NVP/RTV in Step 2 were compared with children receiving RTV
      containing regimens in Step 1. RESULTS: At 24 weeks of treatment with d4T/NVP/RTV
      in Step 2, 48% (23 of 48) of children had HIV RNA < or = 400 copies/ml compared
      with 34% (31 of 92) and 47% (44 of 93) receiving d4T/RTV or ZDV/3TC/RTV for 24
      weeks in Step 1; at 48 weeks virologic response was 44, 27 and 42% in Step 2
      d4T/NVP/RTV, Step 1 d4T/RTV and Step 1 ZDV/3TC/RTV arms, respectively.
      CONCLUSIONS: A delay of 7 to 12 months in the initiation of protease inhibitor
      containing combination therapy in children receiving dual nucleoside analogue
      therapy did not adversely affect the RNA response during the first 48 weeks of
      treatment.

PMID- 11840079
TI  - Human herpesvirus 6 and cytomegalovirus infections in children with human
      immunodeficiency virus infection and cancer.
AB  - AIM: Measure the prevalence of human herpesvirus 6 (HHV-6) and cytomegalovirus
      (CMV) infections in children and adolescents with HIV infection and malignancy.
      METHODS: Semiquantitative polymerase chain reaction and serology were used to
      test for HHV-6 and CMV infections in 31 cases (HIV-infected children with
      cancer), 56 HIV controls (HIV-infected children without cancer) and 30 cancer
      controls (HIV-uninfected children with cancer). RESULTS: In cases, HIV controls
      and cancer controls, HHV-6 DNA was detected in 29, 39 and 34%, respectively, and
      CMV DNA was detected in 13, 4 and 7%, respectively. Four cases (13%) and no HIV
      controls or cancer controls harbored HHV-6 subtype A (P = 0.014). In cases, HIV
      controls and cancer controls, the prevalence of HHV-6 antibodies was 58, 68 and
      93%, respectively, and the prevalence of CMV antibodies was 71, 48 and 70%,
      respectively. HHV-6 seroprevalence was lower in cases than in cancer controls (P
      = 0.002), even with adjustments for age and CD4 concentrations; however, HHV-6
      infection rates (presence of HHV-6 DNA and/or HHV-6 antibodies) were similar in
      all groups. Stratification showed that CMV infection was more common in younger
      patients (ages < 8 years) without severe immune suppression (CD4 concentration
      >200 cells/microl) than in HIV controls (odds ration, 10.343; 95% confidence
      interval, 1.65, 121.57). Geometric mean titers of serum anti-CMV antibodies, but
      not anti-HHV-6 antibodies, were higher in cases (1:71) than in HIV controls
      (1:33) (P = 0.005). CONCLUSIONS: HHV-6 and CMV infections were common among
      children with HIV infection and cancer. CMV seropositivity also was associated
      with cancer in younger HIV-infected patients who did not have severe immune
      suppression. HHV-6A was detected only in HIV-infected children with cancer.

PMID- 11840080
TI  - Immunogenicity of a recombinant human cytomegalovirus gB vaccine in seronegative
      toddlers.
AB  - BACKGROUND: Immunization of young children against cytomegalovirus (CMV) might
      decrease child-to-child and child-to-adult transmission of CMV and thereby reduce
      maternal infection during pregnancy. We conducted a Phase I trial in CMV
      seronegative toddlers to evaluate the reactogenicity and immunogenicity of a CMV
      gB vaccine administered with MF59, an oil and water adjuvant. METHODS: Eighteen
      children between 12 and 35 months of age received either 20 microg of CMV gB/MF59
      (n = 15) or a control hepatitis A vaccine (n = 3) at 0, 1 and 6 months. The study
      was open-label for the first six children and then observer-blinded and
      randomized. Children were monitored for local and systemic reactions and for the
      development of antibodies to the envelope protein gB and CMV-neutralizing
      antibodies. RESULTS: Adverse reactions were uncommon and mild. Two children were
      excluded from the immunogenicity analysis because they had serologic evidence of
      CMV infection. Reciprocal geometric mean neutralizing titers were: 0
      preimmunization (n = 18); 90 (range, 53 to 188) after Dose 2 (n = 6); and 638
      (range, 210 to 1645) 1 month after Dose 3 (n = 13). The reciprocal geometric mean
      neutralizing titers of antibody to gB by EIA were: 0 preimmunization (n = 18);
      857 (range, 307 to 2073) after Dose 1 (n = 12); 27 457 (range, 9312 to 55,080)
      after Dose 2 (n = 6); and 98,264 (range, 35,480 to 228,780) 1 month after Dose 3
      (n = 5). After Dose 3 antibody responses of toddlers were greater than those of
      naturally infected adults and were notably higher than among 149 adults given 3
      doses of the same vaccine in other trials. CONCLUSION: The CMV gB vaccine is well
      tolerated and highly immunogenic in toddlers.

PMID- 11840081
TI  - Haemophilus influenzae type b conjugate vaccine diluted tenfold in diphtheria
      tetanus-whole cell pertussis vaccine: a randomized trial.
AB  - BACKGROUND: Despite their proven efficacy Haemophilus influenzae type b (Hib)
      conjugate vaccines are not given to most children in the developing world in the
      face of an estimated global Hib disease burden of nearly 2 million cases per
      annum. A major barrier to the introduction of the vaccine would be overcome by
      diluting the vaccine 10-fold in diphtheria-tetanus-whole cell pertussis (DTP). We
      report a randomized trial comparing the use of Hib conjugate vaccine diluted in a
      multidose vial of DTP with that of the full Hib dose. METHODS: We randomized 168
      infants to receive either the full dose Hib polysaccharide-tetanus toxoid
      conjugate (PRP-T) vaccine or a 1/10 dilution prepared by reconstituting the full
      dose in a 10-dose DTP vial. Infants were vaccinated at 6, 10 and 14 weeks of age
      and received a full dose as a test of immunologic memory at 9 months of age. Sera
      were collected at each visit and at 1 week after the booster dose. Serum anti
      capsular PRP antibody concentrations were measured by enzyme-linked immunosorbent
      assay. RESULTS: After the primary vaccination series, 95% of infants in the full
      dose arm and 94% of infants in the 1/10 dose arm achieved anti-PRP IgG antibody
      concentrations of > or = 1.0 microg/ml. Infants receiving the diluted vaccine had
      significantly higher titers of anti-PRP antibody in response to the booster dose
      (151.36 microg/ml vs. 68.55 microg/ml, P = 0.009). CONCLUSIONS: The 1/10 dose of
      PRP-T was as immunogenic and safe as the full dose. The technique of diluting a
      single dose of PRP-T in a 10-dose DTP vial could potentially allow the widespread
      introduction of Hib vaccine in resource-poor countries currently unable to afford
      full dose Hib conjugate vaccine.

PMID- 11840083
TI  - Epidemiology and clinical presentation of respiratory syncytial virus infection
      in a rural area of southern Mozambique.
AB  - BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of lower
      respiratory tract infection (LRTI) in infants throughout most of the world, but
      little is known about RSV infection in Africa where LRTI are among the leading
      causes of infant and childhood death. METHODS: The study took place in a rural
      district hospital in southern Mozambique between October, 1998, and May, 2000.
      From all children (n = 5635) <1 year of age presenting to an outpatient
      department with cough or nasal secretion and all children (n = 1307) <5 years of
      age admitted to hospital with a LRTI, a nasopharyngeal aspirate was collected and
      tested for RSV by enzyme-linked immunosorbent assay (Abbott). RESULTS: RSV
      infection was found in 8.6% of study infants in the outpatient department and
      10.6% of admitted children with LRTI. Cases presented in predictable yearly
      outbreaks during the warm and rainy season. Lower respiratory tract involvement
      was frequent (59.7%). Cough, chest indrawing and increased respiratory rate were
      all independently related to RSV infection. Wheezing was infrequent. Bacterial
      coinfection (4.6%) and the case-fatality rate (3.4%) were low. CONCLUSIONS: There
      is a substantial burden of disease attributable to RSV infection in this rural
      African setting, with the highest incidence and severity occurring in young
      infants.

PMID- 11840082
TI  - Six year multicenter surveillance of invasive pneumococcal infections in
      children.
AB  - OBJECTIVE: Monitor clinical and microbiologic features including antimicrobial
      susceptibility of invasive pneumococcal infections among children. DESIGN: A 6
      year (September, 1993, through August, 1999) prospective surveillance study of
      all invasive pneumococcal infections in children. PATIENTS: Infants and children
      cared for at eight children's hospitals in the United States with culture-proved
      invasive pneumococcal infection. RESULTS: During the 6-year period 2581 episodes
      of invasive pneumococcal infection occurred in 2498 children. Underlying
      conditions were present in 29% of the children. Of children without an underlying
      condition, 15% of the total infections occurred in those 25 to 60 months old. As
      the ages of the children advanced the proportion of cases classified as
      bacteremia declined, whereas the proportion classified as pneumonia increased.
      Also, as the ages of the children increased the proportion of isolates in
      serotypes/serogroups 1, 3 and 23 increased. whereas the proportion for serotype
      14 diminished. During the 6 years of the study, there was a significant increase
      in the percentage of isolates intermediate or resistant to penicillin (P <
      0.000001) or intermediate to ceftriaxone (P < 0.002). By the sixth year of the
      study, 37 and 11% of the isolates were nonsusceptible to penicillin or
      ceftriaxone, respectively. Antibiotic use in the 30 days before diagnosis of
      systemic pneumococcal infection occurred in 30 to 35% of the children for each of
      the 6 years. The overall case-fatality rate for children with systemic
      pneumococcal infection was 1.56%. Mortality was greatest in children >60 months
      old and in those with underlying conditions; mortality was not related to
      antibiotic susceptibility. CONCLUSIONS: The percentage of pneumococcal isolates
      recovered from children with systemic infection which were intermediate for
      penicillin or ceftriaxone or resistant to penicillin increased steadily during
      the 6-year period. There was also a trend toward increasing rates of resistance
      to ceftriaxone. The age and serogroup/serotype distributions of our patients
      support the recommendations to consider administration of the seven valent
      pneumococcal conjugate vaccine for all children 24 to 59 months old, with special
      consideration for selected groups.

PMID- 11840084
TI  - Management of typhoid fever in children.

PMID- 11840085
TI  - Immunization in transplant patients.

PMID- 11840086
TI  - Trichosporonosis, an unusual fungal infection in neonates.

PMID- 11840087
TI  - Streptococcus pyogenes pyomyositis.
AB  - Group A beta-hemolytic Streptococcus pyomyositis continues to be an uncommon
      disease. We present a case of a 7-year-old boy with an M protein type 1,
      streptococcal pyrogenic exotoxin A and B, Streptococcus pyogenes pyomyositis and
      streptococcal toxic shock syndrome.

PMID- 11840088
TI  - Trichosporon asahii: an unusual cause of invasive infection in neonates.
AB  - Trichosporon asahii causes white piedra, an infection of hair shafts and
      onychomycosis in immunocompetent patients, as well as various localized or
      disseminated invasive infections in immunodeficient hosts. We describe a 26-week
      gestation 890-g vaginally delivered female neonate who had severe respiratory
      distress syndrome and on the sixth day of life developed Klebsiella pneumoniae
      sepsis. At the same time two blood cultures were positive for T. asahii. The
      neonate was also colonized with T. asahii in the pharynx and perineum. The infant
      was successfully treated with conventional amphotericin B.

PMID- 11840089
TI  - Chronic vulvovaginitis caused by antibiotic-resistant Shigella flexneri in a
      prepubertal child.
AB  - A 7-year 8-month-old girl was diagnosed with a prolonged course of vulvovaginitis
      caused by Shigella flexneri. The child was symptomatic with intermittent vaginal
      bleeding, dysuria and foul smelling vaginal discharge for a 3-year period.
      Initial attempts to resolve the infection with successive courses of antibiotic
      therapy using ampicillin, trimethoprim-sulfamethoxazole, cefixime and
      amoxicillin/clavulanic acid failed. The child's infection was finally resolved by
      a 14-day course of ciprofloxacin.

PMID- 11840090
TI  - Glomerulonephritis after recombinant hepatitis B vaccine.
AB  - Renal complications after vaccination with hepatitis B recombinant vaccine are
      rare; very few cases are reported without a histopathologic definition. We
      describe a case of glomerulonephritis in a 12-year-old girl, beginning after the
      inoculation of hepatitis B vaccine. The immunohistochemical examination of her
      renal biopsy, with the use of monoclonal antibodies, shows the presence of
      hepatitis B surface antigen in renal tissue. After 2 years chronic
      glomerulonephritis persisted and was treated with angiotensin-converting enzyme
      inhibitors. After 3 years of follow-up, the renal disease was in remission, and
      treatment was stopped.

PMID- 11840091
TI  - Influenza B infection associated with encephalitis: treatment with oseltamivir.
AB  - Encephalitis associated with acute influenza infection is unusual in nonepidemic
      years. A case of a 10-year-old child with influenza B encephalitis and profound
      weakness who was treated with oseltamivir is presented. This case illustrates
      several of the unusual findings associated with influenza infections and the
      result of treatment of influenza B encephalitis with oseltamivir.

PMID- 11840092
TI  - Enterobacter hormaechei bloodstream infection at three neonatal intensive care
      units in Brazil.
AB  - Enterobacter hormaechei was defined as a unique species in 1989. We describe six
      case patients of E. hormaechei bloodstream infection in three neonatal intensive
      care units in Rio de Janeiro, Brazil. E. hormaechei identification was performed
      on the Vitek system and confirmed by conventional testing. Strain relatedness was
      evaluated by pulsed field gel electrophoresis. All children recovered completely.
      Chart review for previous procedures revealed parenteral nutrition as the only
      common procedure.

PMID- 11840094
TI  - Herpes zoster during varicella.

PMID- 11840093
TI  - Infected cardiac myxoma.
AB  - Infected cardiac myxoma is a rare condition with variable presentation. We report
      a case of infected cardiac myxoma which presented as fever of unknown origin.
      Diagnostic considerations and treatment of this condition are discussed.

PMID- 11840095
TI  - Streptococcal fasciitis causing phlegmasia cerulea dolens.

PMID- 11840097
TI  - Perioperative use of corticosteroid and bupivacaine combination in lumbar disc
      surgery: a randomized controlled trial.
AB  - STUDY DESIGN: A prospective and controlled study of perioperative use of combined
      local anesthetic and corticosteroid in lumbar disc surgery. SUMMARY OF BACKGROUND
      DATA: The anti-inflammatory mechanism of corticosteroids is considered to be
      caused by the inhibition of phospholipase A2, which plays an important role in
      the pain mechanism of lumbar disc problems. Although some authors have
      demonstrated that the use of intramuscular bupivacaine during lumbar discectomy
      resulted in a marked reduction of postoperative back pain, others have reported
      that the key intervention was probably the administration of epidural
      corticosteroid. The coadministration of these two drugs in lumbar disc surgery
      for the relief of postoperative back pain has yet not been studied adequately.
      OBJECTIVES: Assessment of the combined use of perioperative corticosteroids and
      bupivacaine for the relief of postoperative pain after lumbar disc surgery.
      METHODS: Forty-four selected patients had acute-onset single-level unilateral
      herniated nucleus pulposus that were refractory to conservative management. All
      patients underwent lumbar disc surgery under standard general anesthesia. Before
      surgical incision, the skin and subcutaneous tissues were infiltrated with 10 mL
      of 1% lidocaine with 1:200,000 adrenaline to produce local vasoconstriction.
      During wound closure, 20 mL 0.9% saline in Group 1 (n = 22) and 20 mL 0.25%
      bupivacaine in Group 2 (n = 22) were injected into the paravertebral muscles and
      subcutaneus tissues. In addition, a piece of autologous fat taken from the wound
      was first soaked in 40 mg of methylprednisolone for 10 minutes, then placed over
      the exposed nerve root, and the remaining steroid was flushed into the wound in
      Group 2. The wound was closed after drug administration in both groups. In the
      postoperative period, all patients received 100 mg of meperidine intramuscularly
      when needed and were allowed to receive a second dose at least 4 hours later than
      the first dose for postoperative analgesia. Postoperative back pain intensity,
      heart rate, and mean arterial pressure were assessed 1, 3, 6, and 12 hours after
      the conclusion of surgery. RESULTS: Visual analog scale pain scores for the
      postoperative recordings were lower in Group 2 than in Group 1, but these
      findings were not statistically significant. Patients in Group 1 received 77.3 +/
      48.8 mg meperidine, and those in Group 2 received 31.8 +/- 45.5 mg meperidine,
      for pain medication in the first 12 hours (P < 0.05). Heart rate and mean
      arterial pressure were not significantly different between the two groups in all
      recording periods. CONCLUSION: It is concluded that the perioperative use of
      bupivacaine and corticosteroids during lumbar discectomy maintains effective
      postoperative analgesia and decreases opioid usage without complications.

PMID- 11840098
TI  - The vascular pattern of the human dorsal root ganglion and its probable bearing
      on a compartment syndrome.
AB  - STUDY DESIGN: A descriptive anatomic investigation of the vasculature of the
      dorsal root ganglions. OBJECTIVES: To determine whether the blood supply of the
      various spinal ganglions is sufficiently consistent to derive a "generic"
      description and illustration that would be applicable to all spinal levels, and
      to ascertain whether this vascular pattern is inherently predisposed to the
      development of a closed compartment syndrome. SUMMARY OF BACKGROUND DATA: The few
      previous descriptions of spinal ganglionic vasculature do not include
      photographic evidence showing uniformity in the arterial distribution plan at all
      ganglionic levels. The venous drainage, although verbally reconstructed from
      microscopic sections, lacks any indication of its probable role in the etiology
      of a compartment syndrome. METHODS: Three perinatal cadavers received latex/India
      ink injections, and their removed radiculomedullary systems were cleared,
      transilluminated, and macroscopically photographed. Paravertebral sections were
      grossly removed from the spines of two adult anatomic cadavers and received
      retrograde venous injections of a fine suspension of barium sulfate. The
      intervertebral foraminal tissues were then dissected from the bone, and
      radiographs of them were made. For comparative reference, a nerve root/ganglion
      complex of a rabbit was arterially injected with a more dilute preparation of the
      latex/India ink suspension. RESULTS: Macroscopic photographs of perinatal dorsal
      root ganglions showed that the pattern of the intraganglionic arterial
      distribution was sufficiently consistent to allow a graphic rendering and
      labeling of a "generic" ganglion. The series of incomplete retrograde venous
      injections adequately indicated the pressure labile location of a periganglionic
      venous plexus. CONCLUSIONS: The common development, structure, and function of
      the human dorsal root ganglions have resulted in the evolution of a uniform
      nutritional vascular pattern that can be conceptualized in a single visual image.
      Its plan of a primarily internal arterialization with a superficial venous
      drainage renders it vulnerable to the ischemic conditions consequent on external
      pressures and/or internal edematous swelling. This vascular arrangement may
      contribute to a propensity for the ganglion to develop a compartment syndrome
      when subjected to compression by periforaminal degenerative or neoplastic space
      occupying lesions.

PMID- 11840099
TI  - Delivery of recombinant human bone morphogenetic protein-2 using a compression
      resistant matrix in posterolateral spine fusion in the rabbit and in the non
      human primate.
AB  - STUDY DESIGN: A rabbit and rhesus monkey model of posterolateral intertransverse
      process spine arthrodesis was used. OBJECTIVE: To test two new soft tissue
      compression resistant ceramic/collagen sponge carriers for recombinant human bone
      morphogenetic protein-2. SUMMARY OF BACKGROUND DATA: After determining that a
      plain collagen sponge was too compressible for large animals in a posterolateral
      fusion application, the authors demonstrated good bone induction using biphasic
      ceramic phosphate granules (60% hydroxyapatite/40% tricalcium phosphate) as the
      carrier matrix for recombinant human bone morphogenetic protein 2 in rhesus
      monkeys. A limitation of 60:40 biphasic ceramic phosphate was its slow resorption
      time caused by the high hydroxyapatite content, making radiographic detection of
      new bone formation very difficult. METHODS: Adult New Zealand white rabbits (n =
      14) underwent posterolateral spine arthrodesis at L5-L6 using 5:95 biphasic
      ceramic phosphate (5% hydroxyapatite/95% tricalcium phosphate) impregnated Type I
      collagen sponges (17 x 35 x 2.5 mm, two per side) loaded with 0.86 mg recombinant
      human bone morphogenetic protein 2. Additional rabbits (n = 14) received 60:40
      hydroxyapatite-tricalcium phosphate granules as the carrier for bone
      morphogenetic protein 2. Adult rhesus monkeys (n = 6) underwent posterolateral
      arthrodesis at L4-L5 with ceramic/collagen sponge carrier loaded with 9 mg
      recombinant human bone morphogenetic protein 2 per side. Two monkeys received
      ceramic/collagen sponges containing 15:85 biphasic ceramic phosphate (15%
      hydroxyapatite/85% tricalcium phosphate) with two pieces per side; two received
      sponges containing 5:95 biphasic ceramic phosphate with two pieces per side, and
      two received sponges containing 5:95 biphasic ceramic phosphate with four pieces
      per side. The rabbits were killed after 5 weeks and the monkeys after 24 weeks;
      the spines were evaluated by manual palpation, radiographs, tensile mechanical
      testing (rabbits only), and histology. RESULTS: The recombinant human bone
      morphogenetic protein 2 delivered in the 5:95 biphasic ceramic phosphate/collagen
      sponge achieved fusion in 100% of rabbits and had improved handling properties
      compared with the biphasic ceramic phosphate granules. Biomechanical results with
      5:95 biphasic ceramic phosphate/collagen carrier were comparable to those
      obtained with the 60:40 biphasic ceramic phosphate granules and superior to those
      of autogenous bone graft (P < 0.05). The recombinant human bone morphogenetic
      protein 2 delivered in the 15:85 or the 5:95 biphasic ceramic phosphate/collagen
      sponge carrier (two pieces per side) induced fusion in nonhuman primates with
      normal bone histology, less residual ceramic, and more bone in the center of the
      carrier matrix in comparison with BCO granules alone. The 15:85 biphasic ceramic
      phosphate/collagen sponge resulted in fusion mass sizes closer to the original
      size of the matrix implanted than did the 5:95 biphasic ceramic
      phosphate/collagen sponge, which was considered a desirable feature. The monkeys
      with 9 mg recombinant human bone morphogenetic protein 2 spread over four sponges
      per side instead of two had half the effective recombinant human bone
      morphogenetic protein 2 concentration per sponge and inferior results.
      CONCLUSIONS: The new compression-resistant biphasic ceramic phosphate/collagen
      sponge matrices were biologically compatible with recombinant human bone
      morphogenetic protein 2 bone formation, resulted in biomechanically stiffer
      fusion masses than autograft, better space maintenance than plain collagen
      sponges, and improved handling and radiographic resorption properties over the
      ceramic carriers previously tested.

PMID- 11840100
TI  - A comparative study of localization of heat shock protein 27 and heat shock
      protein 72 in the developmental and degenerative intervertebral discs.
AB  - STUDY DESIGN: The lumbar intervertebral discs of 135 subjects after autopsy were
      immunostained with antihuman heat shock protein 27 (HSP27) monoclonal antibody
      and antihuman heat shock protein 72 (HSP72) polyclonal antibody. OBJECTIVES: To
      present the data on metabolic changes that occurred in the chondrocytes of
      intervertebral discs during development and aging. SUMMARY OF BACKGROUND DATA:
      Heat shock proteins have been implicated in the progressive degeneration of
      articular cartilage in joint disease, such as rheumatoid arthritis and
      osteoarthritis. However, the role and expression of heat shock proteins in human
      intervertebral discs have received little study. METHODS: One hundred thirty-five
      specimens of human intervertebral discs were stained with hematoxylin and eosin,
      alcian blue, and Masson's trichrome and were immunostained with HSP27 and HSP72
      by an indirect immunoperoxidase method. The relative amounts of HSP27 and HSP72
      deposition were graded according to a semiquantitative scoring system. RESULTS:
      Heat shock protein 72 accumulated in the cytoplasm of the chondrocytes of both
      endplate cartilage and nucleus pulposus during gestation and thereafter decreased
      with aging (age, </=60 years), and HSP72 immunoreactivity increased in the
      chondrocytes of degenerative discs. In addition, HSP72 was located in the nuclei
      of certain chondrocytes of the degenerated nucleus pulposus and anulus fibrosus,
      was highly expressed in the chondrocytes of endplate cartilage during gestation
      and childhood, and thereafter decreased with aging. Furthermore, with the
      progressive degeneration of the endplate cartilage, HSP27 immunoreactivity
      increased. The degree of HSP27 immunoreactivity did not change significantly
      according to age in either the nucleus pulposus or the anulus fibrosus.
      CONCLUSIONS: Heat shock protein 27 and HSP72 are thus considered to be useful
      molecular indicators for degenerative change in intervertebral discs. Both HSP27
      and HSP72 are presumed to play a role in cell protection from stress that is
      induced by mechanical and biologic factors causing intervertebral disc
      degeneration.

PMID- 11840101
TI  - Point of view.

PMID- 11840102
TI  - Central and juxta-endplate vertebral body screw placement: a biomechanical
      analysis in a human cadaveric model.
AB  - STUDY DESIGN: In vitro biomechanical testing of transvertebral body screws in
      different positions in both axial pull-out and toggle. OBJECTIVES: To determine
      the relative strength of unicortical versus bicortical screw fixation within the
      vertebral body and to determine comparative strength of juxta-endplate and
      central screw positions with and without staples in both axial pull-out and
      toggle modes. SUMMARY OF BACKGROUND DATA: Loss of fixation is common in centrally
      placed screws at the rostral end of a construct. To preserve segmental vessels,
      juxta-endplate screw positions are often used. The biomechanical strength of such
      screw placement methods has not been measured. METHODS: Eighty-three human
      cadaveric vertebral bodies were tested for axial pull-out and toggle with and
      without staples. Screw positions included central, juxta superior, and inferior
      endplate. Juxta-endplate screws were toggled in both the rostral and caudal
      directions perpendicular to the screw axes. RESULTS: Unicortical fixation
      resulted in a 93% decrease in axial pull-out strength compared with bicortical
      fixation. Centrally placed screws and juxta-endplate screws were equivalent in
      axial pull-out if no staples were used. The juxta-endplate screw with a staple
      that was toggled away from the endplate had the highest yield strength, followed
      by the central screw with a staple, and then the juxta-endplate screw without a
      staple toggled away from the endplate. CONCLUSIONS: Bicortical fixation is much
      stronger than unicortical fixation. Centrally placed screws are significantly
      stronger when used with a staple. When preservation of segmental vessels is
      desirable, juxta-endplate screws should be placed in such a manner that
      compressive forces are directed away from the endplate.

PMID- 11840103
TI  - Clinical outcome in chordoma: utility of flow cytometry in DNA determination.
AB  - STUDY DESIGN: A retrospective review of 100 patients with chordoma of the lumbar
      spine and sacrum. Twenty-three patients had flow cytometry data available and a
      minimum follow-up period of 5 years. OBJECTIVES: To determine whether DNA content
      and cell cycle analysis were associated with patient outcome. SUMMARY OF
      BACKGROUND DATA: DNA flow cytometry has been shown to be predictive for biologic
      behavior of various tumors. Chordoma has been evaluated in very small numbers of
      patients using DNA flow cytometric analysis, and the utility of DNA patterns in
      predicting outcome has not been clearly demonstrated. METHODS: Between January
      1979 and December 1995, 100 patients underwent surgical resection for chordoma,
      and 23 had a minimum follow-up period of 5 years with flow cytometry data. DNA
      content and cell cycle analysis were determined by enzymatically staining cells
      with propidium iodide dye and passing them through a flow cytometer. DNA
      histograms were generated. Survivorship and freedom from local recurrence curves
      were constructed by the Kaplan-Meier method and compared by the log-rank test.
      RESULTS: The mean follow-up period was 7.3 years. For this group of 23 patients,
      mortality was 61% (14 patients) and local recurrence was 78% (18 patients).
      Eleven patients had tumors with diploid DNA content, and 12 patients had tumors
      with aneuploid DNA content. Metastases occurred in 4 of the 11 patients with a
      diploid pattern and 6 of the 12 with an aneuploid pattern. Six of the 11 patients
      with the diploid pattern died, in comparison with 8 of 12 patients with the
      aneuploid pattern. The Kaplan-Meier estimated survivorship (95% confidence
      interval) was 78% (66-90%) at a follow-up period of 5 years and 36% at a follow
      up period of 10 years (22-50%), and no significant differences were found between
      patients with diploid and aneuploid patterns. CONCLUSIONS: Patients in whom
      metastases did not develop had a more favorable clinical outcome. DNA pattern was
      not associated with local recurrence or survival.

PMID- 11840104
TI  - Glycosphingolipid antibodies in serum in patients with sciatica.
AB  - STUDY DESIGN: Serum antibody titers against 10 different glycosphingolipids were
      investigated by enzyme-linked immunosorbent assay in three groups of patients:
      patients with acute sciatica (Group IA, radicular pain for 32 +/- 36 days, n =
      68), a subgroup of these patients 4 years later (Group IB, n = 23), and patients
      undergoing lumbar discectomy because of disc herniation (Group II, n = 37).
      OBJECTIVES: To investigate the immunologic response in sciatica patients by
      analyzing circulating autoantibodies against glycosphingolipids, molecules highly
      expressed in cells from the nervous system, and the possible correlation of such
      antibodies to clinical and imaging findings as well as to subjective symptoms.
      SUMMARY OF BACKGROUND DATA: The titers of glycosphingolipid antibodies are
      elevated in neurologic diseases with autoimmune stimulation such as Guillain
      Barre syndrome and chronic inflammatory demyelinating polyneuropathy. METHODS:
      Antiglycosphingolipid antibodies were assayed by a microtiter enzyme-linked
      immunosorbent assay method. Antibody titers were related to a healthy population
      by a method that judges all positive results (positive result = patient
      sera/pooled blood donor serum >2, at titer 1/400) as indicating a pathologic
      condition. RESULTS: Increased levels of circulating antibodies against one or
      more glycosphingolipids were detected in 71% of patients with acute sciatica, in
      61% of sciatica patients at a 4-year follow-up visit (eight antigens analyzed)
      and in 54% in patients undergoing discectomy. These frequencies were somewhat
      higher than, and in the last group similar to, those reported for generalized
      nervous system disorders with autoimmune involvement. In the acute sciatica
      patients, positive neurologic findings were associated with increased levels of
      two of the examined antibodies: 3'LM1 (immunoglobulin M and/or immunoglobulin G),
      P = 0.023, and GD1a (immunoglobulin M), P = 0.017. CONCLUSION: The presence of
      glycosphingolipid antibodies in patients with sciatica and disc herniation
      suggests an activation of the immune system and thus a process possibly involved
      in the pathophysiology of sciatica. The autoimmune response was not limited to
      antibodies against one specific glycosphingolipid target; rather, an overall
      increase in autoantibodies against nervous system-associated glycosphingolipids
      was observed. These results encourage further studies of the pathophysiologic and
      clinical relevance of autoimmune responses in patients with sciatica and disc
      herniation.

PMID- 11840105
TI  - Adult scoliosis: a quantitative radiographic and clinical analysis.
AB  - STUDY DESIGN: Prospective analysis of a consecutive series of adult patients with
      adolescent idiopathic scoliosis of the adult and de novo degenerative scoliosis.
      OBJECTIVES: To clinically and radiographically study two populations of adult
      patients with either adolescent idiopathic scoliosis of the adult or de novo
      degenerative scoliosis in a quantitative manner to identify reliable radiographic
      parameters that correlate with clinical symptoms. SUMMARY AND BACKGROUND:
      Although there are many causes of spinal deformity in the adult, there are two
      main categories of adult scoliosis: adolescent idiopathic scoliosis of the adult
      and de novo degenerative scoliosis. Unlike pediatric scoliosis, in adults there
      are no established radiographic parameters or classification systems that
      reliably provide a clinical correlation or offer a useful language for
      communication among specialists. This study gathered complete clinical and
      radiographic information on 95 patients with adult scoliosis and established
      several radiographic parameters that correlated with clinical symptoms. METHODS:
      Each of the 95 patients completed a clinical questionnaire that included a self
      reported visual analog scale and underwent full-length standing anteroposterior
      and lateral radiography. Radiographic analysis was performed by use of digital
      analysis and included measurement of the Cobb angle, the number of vertebrae in
      each curve, plumbline offset from T1 to the midsacral line, the upper endplate
      obliquities of L3 and L4, and maximal lateral olisthy between two adjacent lumbar
      vertebrae. Sagittal plane measurements included lumbar lordosis, thoracolumbar
      kyphosis, and the Sagittal Pelvic Tilt Index. Statistical analysis of both
      radiographic and clinical parameters of pain was performed to determine any
      significant correlations between the two. RESULTS: This study showed that lateral
      vertebral olisthy, L3 and L4 endplate obliquity angles, lumbar lordosis, and
      thoracolumbar kyphosis were significantly correlated with pain. CONCLUSION: This
      quantitative analysis identified several clinically relevant radiographic
      parameters in adult scoliosis patients. Additionally, excellent predictive
      formulas for self-reported pain levels were obtained.

PMID- 11840106
TI  - Hyperrotatory paradoxic kyphosis.
AB  - STUDY DESIGN: A retrospective radiographic evaluation of 32 patients with
      hyperrotatory scoliosis accompanied by paradoxic hyperkyphosis, who were treated
      with posterior multilevel hook instrumentation. OBJECTIVES: To give a three
      dimensional analysis of this particular deformity and to evaluate the coronal,
      sagittal, and horizontal plane corrections in these specific curves. SUMMARY OF
      BACKGROUND DATA: Lordoscoliosis with a severe rotational component produces
      paradoxic kyphosis in the sagittal plane. A vertebral derotational maneuver is
      essential to restore the normal sagittal alignment. METHODS: Thirty-two patients
      were treated with posterior multilevel hook instrumentation. Nine patients had
      previously undergone anterior release and fusion. The derotational maneuver could
      be accomplished in 21 cases. The coronal Cobb angle and the extents of apical
      vertebral rotation, sagittal hyperkyphosis, upper and lower compensatory
      lordosis, and sagittal trunk balance were measured after an average follow-up
      period of 5 years and 9 months. RESULTS: The mean coronal deformity decreased
      from 89.9 degrees before surgery to 40.7 degrees. The mean preoperative
      hyperkyphosis was 70.9 degrees in the thoracic spine, 45.9 degrees in the
      thoracolumbar spine, and 55 degrees in the lumbar region. These values were
      reduced to 39.7 degrees, 6.8 degrees, and -15 degrees, respectively. The lateral
      spinal balance changed from -21.3 mm to -8.5 mm. The average rotational
      correction measured by the method of Jackson was 51% before surgery and 39% after
      surgery (correction: 23.5%). There was a positive correlation between the
      preoperative kyphosis angle and the apical rotation (r = 0.58) and between the
      decrease of kyphosis and the correction of the rotation (r = 0.67) in cases when
      the derotational maneuver could be accomplished. CONCLUSIONS: If the apex of the
      scoliosis and the kyphosis are on the same level, the vertebral hyperrotation is
      responsible for the sagittal malalignment. Satisfactory results can be achieved
      with posterior multilevel hook instrumentation.

PMID- 11840107
TI  - The relation between the transversus abdominis muscles, sacroiliac joint
      mechanics, and low back pain.
AB  - STUDY DESIGN: Two abdominal muscle patterns were tested in the same group of
      individuals, and their effects were compared in relation to sacroiliac joint
      laxity. One pattern was contraction of the transversus abdominis, independently
      of the other abdominals; the other was a bracing action that used all the lateral
      abdominal muscles. OBJECTIVES: To demonstrate the biomechanical effect of the
      exercise for the transversus abdominis known to be effective in low back pain.
      SUMMARY OF BACKGROUND DATA: Drawing in the abdominal wall is a specific exercise
      for the transversus abdominis muscle (in cocontraction with the multifidus),
      which is used in the treatment of back pain. Clinical effectiveness has been
      demonstrated to be a reduction of 3-year recurrence from 75% to 35%. To the
      authors' best knowledge, there is not yet in vivo proof of the biomechanical
      effect of this specific exercise. This study of a biomechanical model on the
      mechanics of the sacroiliac joint, however, predicted a significant effect of
      transversus abdominis muscle force. METHODS: Thirteen healthy individuals who
      could perform the test patterns were included. Sacroiliac joint laxity values
      were recorded with study participants in the prone position during the two
      abdominal muscle patterns. The values were recorded by means of Doppler imaging
      of vibrations. Simultaneous electromyographic recordings and ultrasound imaging
      were used to verify the two muscle patterns. RESULTS: The range of sacroiliac
      joint laxity values observed in this study was comparable with levels found in
      earlier studies of healthy individuals. These values decreased significantly in
      all individuals during both muscle patterns (P < 0.001). The independent
      transversus abdominis contraction decreased sacroiliac joint laxity (or rather
      increased sacroiliac joint stiffness) to a significantly greater degree than the
      general abdominal exercise pattern (P < 0.0260). CONCLUSIONS: Contraction of the
      transversus abdominis significantly decreases the laxity of the sacroiliac joint.
      This decrease in laxity is larger than that caused by a bracing action using all
      the lateral abdominal muscles. These findings are in line with the authors'
      biomechanical model predictions and support the use of independent transversus
      abdominis contractions for the treatment of low back pain.

PMID- 11840108
TI  - Physiotherapy management of low back pain: a survey of current practice in
      northern Ireland.
AB  - STUDY DESIGN: A questionnaire survey of physiotherapists treating low back pain.
      OBJECTIVE: To investigate current clinical practice in the physiotherapeutic
      management of low back pain in Northern Ireland. SUMMARY OF BACKGROUND:
      Physiotherapists play an important role in the management of low back pain.
      However, there is relatively limited evidence about physiotherapy or about
      current physiotherapeutic management of low back pain. This survey aimed to
      establish current practice in this area. METHODS: Two sets of questionnaires were
      completed by physiotherapists during the period 1996-1997: one in relation to
      their professional profile, and subsequently a questionnaire for each patient
      referred by physicians to physiotherapy departments in the (government-funded)
      National Health Service in Northern Ireland. RESULTS: Physiotherapists (n = 157)
      recorded data for 1062 patients treated for low back pain in 35 outpatient
      centers across Northern Ireland. Of the patients treated, 70% had a duration of
      current episode more than 6 weeks; 26% of patients had previously received
      physiotherapy for low back pain. Physiotherapy treatment most commonly involved
      advice (89% of patients), McKenzie treatment (70%), Maitland mobilizations (42%),
      and interferential therapy (30.3%). CONCLUSION AND DISCUSSION: Physiotherapists
      typically treated subacute and chronic patients, principally using some types of
      manual techniques and advice, in keeping with current guidelines. However, high
      levels of the use of electrotherapy, and only limited use of manipulation,
      indicates the importance of further research to establish optimum management for
      this group of patients.

PMID- 11840109
TI  - Clinical practice guideline for the physiotherapy of patients with whiplash
      associated disorders.
AB  - STUDY DESIGN: A clinical practice guideline. OBJECTIVES: To assist
      physiotherapists in decision making and to improve the efficacy and uniformity of
      care for patients with whiplash-associated disorders Grades I and II. SUMMARY OF
      BACKGROUND DATA: Whiplash constitutes a considerable problem in health care. Many
      interventions are used in physiotherapy practice, despite increasing evidence for
      the use of active interventions. There is still no clinical practice guideline
      for the management of patients with whiplash-associated disorders. METHOD OF
      DEVELOPMENT: A computerized literature search of Medline, Cinahl, Cochrane
      Controlled Trial Register, Cochrane Database of Systematic Reviews, and the
      Database of the Dutch National Institute of Allied Health Professions was
      performed to search for information about the diagnostic process and the
      therapeutic process in whiplash patients. When no evidence was available,
      consensus between experts was achieved to develop the guideline. Practicing
      physiotherapists reviewed the clinical applicability and feasibility of the
      guideline, and their comments were used to improve it. RECOMMENDATIONS: The
      diagnostic process consists of systematic history taking and a physical
      examination supported by reliable and valid assessment tools to document symptoms
      and functional disabilities. The primary goals of treatment are a quick return to
      normal activities and the prevention of chronicity. Active interventions such as
      education, exercise therapy, training of functions, and activities are
      recommended according to the length of time since the accident and the rate of
      recovery. The biopsychosocial model is used to address the consequences of
      whiplash trauma. CONCLUSIONS: Scientific evidence for the diagnosis and
      physiotherapeutic management of whiplash is sparse; therefore, consensus is used
      in different parts of the guideline. The guideline reflects the current state of
      knowledge of the effective and appropriate physiotherapy in whiplash patients.
      More and better research is necessary to validate this guideline in the future.

PMID- 11840110
TI  - Athletic activity after spine surgery in children and adolescents: results of a
      survey.
AB  - STUDY DESIGN: Questionnaire-based survey. OBJECTIVES: To poll the members of the
      Scoliosis Research Society regarding their opinions and experience with athletic
      activity after spine surgery performed on children and adolescents. SUMMARY OF
      BACKGROUND DATA: Athletic activity is increasingly important in society. Patients
      are very concerned about returning to sports and exercise after spinal surgery.
      There are no generally accepted guidelines for surgeons regarding either
      appropriate sports or the appropriate time to resume sports after spinal surgery.
      METHODS: A survey was designed by the authors and reviewed by a statistical
      consultant. The form was mailed to the 721 individuals on the Scoliosis Research
      Society mailing list. Returned surveys were hand scored and entered into an Excel
      spreadsheet. RESULTS: Of the 316 forms returned, 278 indicated that the
      respondent performed spinal fusion on children and adolescents. Two hundred sixty
      one completed forms, representing approximately 45% of the society's estimated
      active clinicians, were reviewed. Formal physical therapy was unlikely to be
      recommended by members of the society regardless of procedure, although
      postoperative home exercise was used by many after spondylolisthesis fusion. The
      majority of patients were returned to gym class between 6 months and 1 year
      (range, immediate to never) after surgery. Most respondents returned patients to
      noncontact sports between 6 months and 1 year postoperatively. Contact sports
      were generally withheld until 1 year after surgery. Close to 20% of respondents
      required, and 35% suggested, that patients never return to collision sports.
      Twenty percent of respondents for scoliosis and 5% for spondylolisthesis reported
      having notable adverse outcomes attributed to athletic activity. CONCLUSION:
      These survey results show the varying approaches taken by members of the
      Scoliosis Research Society to postoperative athletic activity, and they provide a
      starting point for investigations regarding alternative approaches.

PMID- 11840111
TI  - Complications related to hydroxyapatite vertebral spacer in anterior cervical
      spine surgery.
AB  - STUDY DESIGN: This is a report of complications related to the hydroxyapatite
      vertebral spacer used for anterior cervical reconstructive surgery. Compression
      of the spinal cord by broken fragments of hydroxyapatite spacer as well as its
      surrounding radiolucent clear zone were observed in seven patients. OBJECTIVES:
      To report complications related to the use of hydroxyapatite vertebral spacer for
      anterior cervical reconstructive surgery and to discuss how to prevent these
      complications. SUMMARY OF BACKGROUND DATA: Despite previous articles reporting
      the clinical applications of hydroxyapatite vertebral spacer for the cervical
      spine, clinical reports regarding the long-term results of hydroxyapatite spacer
      for anterior cervical surgery and its complications have been limited. METHODS:
      The authors reviewed patients who underwent anterior reconstructive surgery using
      the hydroxyapatite spacer at other hospitals and had postoperative complications
      related to hydroxyapatite spacer. RESULTS: Seven patients previously treated by
      anterior cervical spine surgery using the hydroxyapatite vertebral spacer were
      referred to the authors because of unsatisfactory surgical outcomes. All the
      patients had a radiolucent clear zone around the spacer and experienced severe
      neck pain. Four had fracture of the hydroxyapatite spacer, and two had
      compression of the spinal cord by retropulsed fragments of broken hydroxyapatite
      spacers. CONCLUSIONS: Although hydroxyapatite has been used in many medical
      fields because of its bioactive characteristics, its mechanical properties should
      be improved to lessen the risks of breakage and subsequent spinal cord
      compression. Gentle insertion maneuvers are also important to avoid the
      production of cracks inside the spacer.

PMID- 11840112
TI  - A minimally invasive technique for decompression of the lumbar spine.
AB  - STUDY DESIGN: The technical feasibility of percutaneous microendoscopic bilateral
      decompression of lumbar stenosis via a unilateral approach was evaluated in a
      human cadaver model. OBJECTIVES: The purpose of this study was to determine the
      feasibility of using a microendoscopic laminotomy technique to treat spinal
      stenosis. SUMMARY AND BACKGROUND DATA: Minimally invasive surgery is an important
      means of reducing tissue trauma and patient morbidity. This may prove to be
      essential in improving pain and in reducing postoperative stress responses and
      delayed sequelae that can lead to unfortunate complications after otherwise
      uneventful procedures. To date, minimally invasive lumbar endoscopic techniques
      have not been used to decompress the lumbar spinal canal. METHODS: In each of
      four cadavers, the laminae of L1 through L4 were subjected to one of four
      procedures consisting of unilateral microendoscopic laminotomy, bilateral
      microendoscopic laminotomy, unilateral open laminotomy, and bilateral open
      laminotomy. Every procedure was performed once at all levels. Computed tomography
      was performed before and after laminotomy to establish the extent of
      decompression of the spinal canal, and measurements of the midsagittal,
      interpedicular, and decompression diameters were taken. RESULTS: The four
      procedures were successfully performed at every level. Satisfactory decompression
      of the spinal canal was achieved regardless of the approach used. The exiting
      nerve roots were well visualized when any one of these techniques was used.
      Complications, including dural tears and facet complex instability, were
      independent of the procedure performed. CONCLUSION: Microendoscopic laminotomy
      can be used to decompress the spinal canal as effectively as an open laminotomy
      and may prove to be beneficial in decreasing the complications and morbidity of
      standard treatments for lumbar stenosis.

PMID- 11840113
TI  - Americans with disabilities act: recent and pending u.s. Supreme court decisions
      and implications for spine professionals.
AB  - This article highlights recent and pending United States Supreme Court cases
      interpreting employment provisions of the Americans with Disabilities Act and
      discusses their implications for spine professionals. The implications include
      how Spine readers approach evaluations of employees and job applicants with
      disabilities and workplace accommodations in light of the recent decisions. The
      cases pending before the Supreme Court involve orthopedic impairments and the
      "reasonableness" of certain workplace accommodations. Increasingly, spine
      professionals will be called on to assist in the analysis of these issues. This
      article will familiarize Spine readers with the legal interpretations under the
      Americans with Disabilities Act of "disability," "mitigating measures,"
      "qualified individual," and "reasonable accommodations." It illustrates the ways
      in which spine professionals may be called on to help interpret and apply
      qualification and safety standards under the Americans with Disabilities Act to
      assist individuals, employers, attorneys, and other stakeholders in the
      employment of people with disabilities.

PMID- 11840114
TI  - Anatomic considerations of superior laryngeal nerve during anterior cervical
      spine procedures.
AB  - STUDY DESIGN: Cadavers were dissected anatomically to identify the course of the
      superior laryngeal nerve relative to the spinal column. OBJECTIVE: To illustrate
      the anatomic relation of the SLN with respect to its vulnerability during
      anterior cervical spine procedures. SUMMARY OF BACKGROUND DATA: There is ample
      literature referencing the superior laryngeal nerve with respect to head and neck
      surgery. Detailed descriptions of the anatomy of the recurrent laryngeal nerve
      are quite extensive in both the spine and head and neck literature. To the
      authors' best knowledge, no similar reports have delineated the anatomic relation
      of the superior laryngeal nerve in procedures on the anterior aspect of the
      cervical spine. METHODS: Ten dissections were carried out on human cadavers to
      show the course of the superior laryngeal nerve. Particular attention was
      directed to the internal branch of the superior laryngeal nerve to show the
      overall anatomic relation relative to standard landmarks. These landmarks
      included the superior laryngeal and superior thyroid arteries, the split of the
      superior laryngeal nerve, and the intervertebral disc space. RESULTS: The
      superior laryngeal nerve originates from the vagus nerve in the carotid sheath
      and bifurcates into internal and external branches. Distally, the internal branch
      of the superior laryngeal nerve courses in close proximity with the superior
      laryngeal artery and inserts within 1 cm superior to the superior laryngeal
      artery into the thyrohyoid membrane. With respect to the cervical spine, the
      distal of portion of the internal branch of the superior laryngeal nerve is
      located between the C3 and C4 vertebral bodies. CONCLUSIONS: The internal branch
      of the superior laryngeal nerve supplies innervation to the mucosa of the larynx
      and has an important sensory reflex that serves to protect the lungs from
      aspiration. Injury to this nerve can predispose the patient to life-threatening
      pneumonia. It is therefore imperative for the surgeon to recognize the location
      and course of this nerve to avoid injuring it. Injury most commonly occurs either
      by excessive retraction in different planes or by accidental ligation of the
      nerve.

PMID- 11840115
TI  - Quality of life in women with idiopathic scoliosis.
AB  - STUDY DESIGN: The health-related quality of life of 226 female patients with
      idiopathic scoliosis was compared with that in age-matched general population
      norms. OBJECTIVES: To describe and characterize health-related quality of life in
      women with idiopathic scoliosis, taking into account age, Cobb angle, and brace
      use. SUMMARY OF BACKGROUND DATA: Scoliosis may lead to multiple physical and
      psychosocial impairments depending on its severity. Previous studies have
      assessed generic health measures, functional status, body image, and self-image.
      Health-related quality of life data from patients with idiopathic scoliosis are
      still lacking. METHODS: Women with idiopathic scoliosis completed an age
      appropriate health-related quality of life questionnaire (either the 36-Item
      Short-Form Health Status Survey, SF-36, or the Berner Questionnaire for Well
      Being). The results from this sample were compared with general population norms.
      In univariate and multivariate analyses it was determined whether age, Cobb
      angle, and brace use had an impact on health-related quality of life. RESULTS:
      Compared with the age-matched general population norm, juvenile patients with
      idiopathic scoliosis were unhappier with their lives (P = 0.001). They reported
      more physical complaints (P < 0.001) and had lower self-esteem (P = 0.01) and
      higher depression scores (P = 0.021). Adult patients reported more psychologic (P
      < 0.001) and physical impairment than in the population norm (P < 0.001). These
      results were largely independent of age and Cobb angle. CONCLUSION: The results
      show that health-related quality of life can be impaired in patients with
      idiopathic scoliosis. Therefore, the psychosocial situation should be taken into
      account in the treatment of these patients.

PMID- 11840117
TI  - Metastatic meningioma in the sacrum: a case report.
AB  - STUDY DESIGN: This report describes a 51-year-old woman with a sacral metastatic
      meningioma that originated from an intracranial meningioma. OBJECTIVES: To
      describe an unusual presentation of a metastatic meningioma in the sacrum.
      SUMMARY OF BACKGROUND DATA: Extracranial metastases of meningioma are very rare.
      The phenomenon of metastasis may have more to do with the ability to invade the
      wall of a blood vessel than with the mitotic activity of a tumor. Therefore,
      metastases of the meningioma can occur even with a benign histologic picture in
      the original intracranial meningioma. METHODS: A 51-year-old woman had
      experienced low back pain and sciatica of the left leg for several months. Plain
      radiographs of the lumbosacral spine showed an osteolytic lesion with an
      irregular margin that occupied the left side of the sacrum. Magnetic resonance
      imaging revealed a soft mass invading the left sacrum, ilium, and presacral
      space. RESULTS: Surgical removal of the sacral tumor via an anterior-posterior
      anterior approach was done. Histopathologic examination revealed a metastatic
      meningioma with a meningotheliomatous histologic composition. Sixteen months
      after excision of the metastatic sacral lesion, the patient was ambulating freely
      and experiencing mild constipation and urine retention. CONCLUSIONS: In this case
      of metastatic meningioma in the sacrum, which is the first such report to the
      authors' best knowledge, total excision of the tumor was successful.

PMID- 11840116
TI  - Pelvis-thorax coordination in the transverse plane during walking in persons with
      nonspecific low back pain.
AB  - STUDY DESIGN: Transverse pelvis and thorax rotations were studied during walking
      in 39 patients with nonspecific low back pain and 19 healthy participants.
      OBJECTIVES: To gain insight into the consequences of low back pain for gait and
      to identify clinically useful measures for characterizing the quality of walking
      in patients with low back pain. SUMMARY OF BACKGROUND DATA: Gait studies in
      patients with low back pain have reported a decrease in walking velocity. In
      normal gait, in-phase pelvis-thorax coordination (synchronicity) evolves toward
      antiphase coordination (counterrotation) as walking velocity increases. This
      study examined the effect of walking velocity on pelvis and thorax rotations in
      patients with low back pain. METHODS: Amplitudes of pelvis and thorax rotations
      were calculated, and spectral analyses were performed. Pelvis-thorax coordination
      was characterized in terms of relative Fourier phase, and coupling strength was
      assessed by means of cross-spectral analysis. RESULTS: In comparison with healthy
      participants, relative Fourier phase was significantly smaller in low back pain
      patients for walking velocities of 3.8 km/h and higher, whereas coupling strength
      was significantly higher for velocities from 1.4 to 3.0 km/h. No significant
      group differences were found in amplitude or spectral content of individual
      pelvis and thorax rotations. CONCLUSION: In comparison with healthy participants,
      the gait of patients with low back pain was characterized by a more rigid, less
      flexible pelvis-thorax coordination in the absence of significant differences in
      the kinematics of the component rotations. This result suggests that coordination
      measures are more adequate in assessing quality of walking in patients with low
      back pain than are kinematic measures pertaining to the individual segment
      rotations, and that conservative therapy should use methods aimed at improving
      intersegmental coordination.

PMID- 11840118
TI  - Sacral stress fractures: an unusual cause of low back pain in an athlete.
AB  - STUDY DESIGN: A case report of a sacral stress fracture causing low back pain in
      an athlete. OBJECTIVE: To document the occurrence of sacral stress fractures in
      athletes and to recommend it in the differential diagnosis of low back pain,
      especially in runners and volleyball players. SUMMARY OF BACKGROUND DATA: Low
      back pain is common both in the general population and in athletes. Athletes
      place high physical demands on their bodies, which often lead to stress
      fractures. Sacral stress fractures can cause back pain and are often not included
      in the differential diagnosis of back pain. METHODS: The authors were involved in
      the care and treatment of this patient and reviewed all medical records,
      radiologic tests, and related literature. RESULTS: In a 16-year-old volleyball
      player with a 4-week history of low back pain, magnetic resonance imaging of her
      pelvis revealed a stress fracture of the left sacral ala. She was treated with
      nonsteroidal anti-inflammatory agents, rest, and conditioning exercises and had a
      good functional outcome. CONCLUSION: Sacral stress fractures should be included
      in the differential diagnosis of athletes with low back pain, particularly
      runners and volleyball players. To the authors' best knowledge, this is the first
      report of a volleyball player with a sacral stress fracture. A review of the
      literature yielded 29 cases of sacral stress fractures in athletes, mainly
      runners.

PMID- 11840119
TI  - Why is it necessary to have a latency period (5 to 7 days) before activating the
      distraction osteogenesis procedure?

PMID- 11840120
TI  - ABO working to improve board-certification process.

PMID- 11840123
TI  - Outcome of tooth transplantation: survival and success rates 17-41 years
      posttreatment.
AB  - The literature contains no follow-up studies of transplanted teeth with mean
      observation times exceeding 10 years. This article describes long-term outcomes,
      including gingival and periodontal conditions, and the patients' attitudes about
      treatment and outcome. The material comprised all accessible patients in the
      files of the Department of Orthodontics, University of Oslo, Norway, on whom
      treatment had been performed at least 17 years ago (n = 28). Established clinical
      criteria were used to assess tooth mobility, plaque and gingival indexes, and
      probing pocket depth. Standardized radiography was used to evaluate the presence
      of pathology, pulp obliteration, and root length. Similar recordings were
      obtained from the in situ tooth contralateral to the initial position of the
      grafted tooth. Criteria for determining treatment success were established. All
      patients responded to questions about their treatment using visual analogue
      scales. The mean age at surgery was 11.5 years, and the mean observation period
      was 26.4 years (range, 17-41 years). Of the 33 teeth transplanted in the 28
      patients, 3 teeth were lost after 9, 10, and 29 years, respectively. Therefore,
      the 30 teeth in the 25 patients we examined yielded a survival rate of 90%. The
      success rate was 79% because 2 transplants had ankylosed, and 2 others failed to
      fulfill the proposed criteria. The patients generally responded very favorably
      regarding their perception of the treatment. Their only hesitation was related to
      some discomfort during surgery. It was concluded that survival and success rates
      for teeth autotransplanted when the root is partly developed compare favorably in
      a long-term perspective with other treatment modalities for substituting missing
      teeth.

PMID- 11840124
TI  - Correction of a bilateral maxillary canine-first premolar transposition in the
      late mixed dentition.
AB  - A bilateral maxillary canine-first premolar transposition was treated during the
      late mixed dentition. The correct tooth order was obtained by moving the teeth
      into their proper positions. The treatment mechanics and the sequencing of
      treatment are described.

PMID- 11840125
TI  - Long-term effects of rapid maxillary expansion: a posteroanterior cephalometric
      evaluation.
AB  - The aim of this study was to investigate long-term effects induced by rapid
      maxillary expansion (RME), followed by comprehensive orthodontic treatment, in a
      sample of 42 patients compared with normal growth changes in a sample of 20
      subjects. Treated subjects underwent Haas-type RME with 2 turns a day (0.25 mm
      per turn) until the expansion screw reached 10.5 mm (about 21 days). The Haas
      expander was kept on the teeth as a passive retainer for an average of about 2
      months. Immediately after the Haas expander was removed, fixed standard edgewise
      appliances were placed. Posteroanterior cephalograms were analyzed for each
      subject in both groups at T1 (pretreatment) and at T2 (long-term observation).
      The mean age at T1 was 11 years 10 months for both the treated and the control
      groups. The mean ages at T2 also were comparable (20 years 6 months for the
      treated group, and 17 years 8 months for the control group). The study included
      transverse measurements on dentoalveolar structures, maxillary and mandibular
      bony bases, and other craniofacial regions (nasal, zygomatic, orbital, and
      cranial). RME followed by edgewise appliance therapy appears to be an effective
      procedure to increase transverse facial dimensions in the long term, at both the
      skeletal and the dentoalveolar levels. Significant pretreatment deficiencies in
      maxillary width, maxillary incisor apex width, and maxillary first molar width
      remained corrected at a mean age of about 20 years. The initial deficiency in
      lateroorbital width was also eliminated.

PMID- 11840126
TI  - Efficacy of high condylectomy for management of condylar hyperplasia.
AB  - The purpose of this study was to compare the treatment outcome and long-term
      stability of 2 groups of young adult patients diagnosed with active condylar
      hyperplasia and treated with 2 different surgical methods. Thirty-seven patients
      (19 females and 18 males) met the criteria for inclusion in the study. Group 1 (n
      = 12; average age at surgery, 17.5 years) was treated with orthognathic surgery
      only, while group 2 (n = 25; average age at surgery, 16.7 years) had high
      condylectomy, articular disc repositioning, and orthognathic surgery. All
      patients underwent standardized clinical and radiographic examination at initial
      consultation, immediately before surgery, immediately after surgery, and at
      longest follow-up. Objective evaluation of temporomandibular joint (TMJ) function
      included maximum incisal opening and lateral excursions. Subjective evaluations
      were performed in group 2 for TMJ pain, jaw function, and diet. Lateral
      cephalometric radiographs were evaluated for presurgical and postsurgical
      mandibular growth. There were no statistically significant differences (P >.05)
      between the 2 groups for maximal incisal opening, lateral excursions, or
      subjective jaw function before surgery. Presurgical growth differed significantly
      (P <.05), with group 2 showing more active growth. At the long-term follow-up, no
      differences were found in lateral excursions or subjective jaw function. There
      was a statistically significant difference in maximum incisal opening (P <.01),
      with a greater increase in group 2, as well as a statistically significant
      difference (P <.05) in cephalometric stability, with group 2 being much more
      stable at long-term follow-up. All patients in group 1 grew back into skeletal
      and occlusal Class III relationships and required secondary intervention. Only 1
      patient in group 2 required secondary surgery, involving maxillary surgery to
      correct postsurgical transverse maxillary relapse; the mandible was stable at
      long-term follow-up. The results of this study showed that patients with active
      condylar hyperplasia treated with high condylectomy, articular disc
      repositioning, and orthognathic surgery have stable, predictable outcomes
      compared with those treated with orthognathic surgery alone.

PMID- 11840129
TI  - Tomographic assessment of temporomandibular joint osseous articular surface
      contour and spatial relationships associated with disc displacement and disc
      length.
AB  - The objective of this retrospective study was to determine whether associations
      exist between osseous temporomandibular joint (TMJ) characteristics and TMJ
      internal derangement (disc position and deformation) in an adolescent population.
      Magnetic resonance imaging (MRI) was used to quantitatively determine disc
      position and length in 335 TMJs in 175 subjects (106 female and 69 male) between
      the ages of 7.27 and 20.0 years (mean age, 13.08 years). Nine tomographic
      variables were measured from pretreatment tomograms. Tomographic data were cross
      referenced with MRI data. Male and female samples were evaluated separately.
      Stepwise linear regression identified associations between disc displacement and
      reduced superior joint space, increased posterior joint space, increased anterior
      joint space, and reduced articular eminence convexity (male R(2) value, 0.41;
      female R(2) value, 0.38). Associations between reduced disc length and condylar
      position and eminence flattening were weaker (male R(2) value, 0.16; female R(2)
      value, 0.32). This study demonstrates that TMJ internal derangement is associated
      with functional osseous adaptation within the joint.

PMID- 11840130
TI  - Condylar displacement related to mandibular symphyseal distraction.
AB  - This study was undertaken to determine the true nature of condylar displacements
      associated with mandibular symphyseal distraction osteogenesis. Earlier
      investigators have assumed that each mandibular half rotated about a point near
      the center of each condyle as viewed on a submental radiograph. In a 12-patient
      sample, 10 with tooth-borne symphyseal distraction and 2 with bone-borne
      symphyseal distraction, it was found that each condyle was laterally displaced in
      direct relationship to the amount of symphyseal distraction. The rigidity of the
      distraction appliances and their attachments and the inability of the soft
      tissues and muscular attachments to cause the mandible to undergo compound
      bending require this to be the case. Temporomandibular joints appear to be able
      to accommodate the lateral displacements because symptoms were not introduced,
      or, if present before therapy, distraction did not exacerbate them.

PMID- 11840131
TI  - The accuracy of 4 panoramic units in the projection of mesiodistal tooth
      angulations.
AB  - The purpose of this study was to compare the mesiodistal tooth angulations
      determined with a typodont/skull testing device with the images of mesiodistal
      tooth angulations from 4 contemporary panoramic units (OP 100, Cranex 3+,
      Orthophos, PM 2002 EC). A typodont testing device was constructed, and the true
      mesiodistal tooth angulations relative to an orthodontic archwire were determined
      with a 3-dimensional coordinate-measuring machine and custom-designed software. A
      human skull served as the matrix into which the typodont was fixed for imaging.
      The skull was repeatedly imaged and repositioned 5 times for each panoramic unit.
      The images were scanned and digitized with custom software to determine the image
      mesiodistal angulations. Results revealed that the majority of image angles from
      the 4 panoramic units were statistically significantly different from the true
      angle measurements. However, definite trends were noted among the panoramic
      units. For the maxillary teeth, the images projected the anterior roots more
      mesially and the posterior roots more distally, creating the appearance of
      exaggerated root divergence between the canine and the first premolar. For the
      mandibular teeth, the images projected almost all roots more mesially than they
      really were, with the canine and the first premolar the most severely affected.
      The largest angular difference for adjacent teeth occurred between the mandibular
      lateral incisor and the canine, with relative root parallelism projected as root
      convergence. It was concluded that the clinical assessment of mesiodistal tooth
      angulation with panoramic radiography should be approached with extreme caution
      and with an understanding of the inherent image distortions.

PMID- 11840132
TI  - Treatment outcomes in 3 modes of orthodontic practice.
AB  - This study examined differences in pretreatment severity and treatment outcome
      among orthodontic patients treated in 3 different practice-management modes.
      Samples of pretreatment (T1) and end of treatment (T2) study casts were selected
      from traditional private practices (TPP, 3 offices, 81 cases), a dental
      corporation (COMP, 2 offices, 53 cases), and a dental management service
      organization (DMSO, 1 office, 36 cases). Orthodontic specialists had treated all
      patients. Cases were initially selected on a consecutive start basis. From each
      practice, the first 30 cases satisfying the study criteria were included in the
      sample. The T1 and T2 study casts were evaluated with the PAR and HLD indexes.
      The PAR and HLD indexes showed a high level of agreement on T1 cast scores but
      not on the T2 casts. Mean T1 scores were highest in the COMP cases, followed by
      the DMSO and the TPP cases. T2 scores were lowest in the TPP cases, followed by
      the DMSO and the COMP cases. The percentage of PAR score reduction showed that,
      in all 3 modes, patients were treated to a high standard.

PMID- 11840134
TI  - Digital radiography for the orthodontist.

PMID- 11840133
TI  - Critical assessment of a device to measure incisor crown inclination.
AB  - The aims of this study were to critically assess the use of a disposable device-
      the tooth inclination protractor (TIP)--to record incisor crown inclination and
      to compare its reliability and validity with that of traditional cephalometric
      radiographic analysis. The sample comprised 30 dental students with lateral
      cephalometric radiographs and dental casts. Four examiners were trained and
      calibrated to digitize radiographs and to use intraoral (on patients and dental
      casts) and extraoral (on dental casts) TIPs. The following angles were measured
      on the radiographs: maxillary incisor to maxillary plane, mandibular incisor to
      mandibular plane, maxillary incisor to occlusal plane, and mandibular incisor to
      occlusal plane. Measurements were also made with the TIP: maxillary incisor to
      occlusal plane and mandibular incisor to occlusal plane. All techniques were
      reliable between examiners. There were statistically significant systematic
      differences between the TIP and the radiographic assessments. The following
      differences were found. The TIP tended to record maxillary incisor crown
      inclination an average of 14 degrees less than maxillary incisor to maxillary
      plane. The TIP tended to record mandibular incisor crown inclination as similar
      to mandibular incisor to mandibular plane. The TIP recorded mandibular crown
      inclination 19 degrees less than mandibular incisor to occlusal plane. The
      disposable TIP was shown to be a simple, inexpensive, reliable, and valid method
      of assessing incisor inclination.

PMID- 11840135
TI  - Litigation, legislation, and ethics: I knew him when.

PMID- 11840137
TI  - Fate of chronic myeloid leukemia patients treated with allogeneic bone marrow
      transplantation or chemotherapy and/or interferon at a single center: long-term
      results.
AB  - From April 1981 to February 2000, 105 patients with chronic myeloid leukemia
      (CML) underwent BMT from HLA-identical related donors at a single center. Eighty
      eight patients were in chronic phase (CP), 11 patients in accelerated phase and
      six patients in blast crisis. Ten of these patients received a second BMT (BMT2).
      Comparison of BMT in CP with chemotherapy and/or alpha-IFN (n=70) was also made.
      Patients were given cyclophosphamide (CY) and single-dose TBI (CYTBI, n=38) or
      busulfan (BU) and CY (BUCY, n=67). Overall 54 patients are alive and 52 of them
      are disease-free with a median follow-up of 11.3 (range 1.1-19.4) years. Ten-year
      disease-free survival (DFS) in CP patients was better after BUCY, 61% (95% CI, 47
      68%) than after CYTBI, 41% (95% CI, 23-61%) (P=0.07). For 88 patients who
      received a transplant in CP, results were significantly improved when BMT was
      performed within 1 year after diagnosis (P=0.02) or at an age < or = 25 years old
      (P=0.01). Ten-year survival in patients who received BMT in CP was better than in
      patients treated with chemotherapy (56% vs 10%; P=0.0001) or alpha-IFN-based
      treatment (33%; P=0.09) with survival curves crossing at 4.2 years and at 4
      years, respectively. The probability of DFS after BMT2 was 60% (95% CI, 26-87%).
      CP patients who received BMT after CYTBI had a higher probability of relapse and
      transplant-related mortality than patients receiving BUCY (53% and 58% vs 9% and
      34%; P=0.002 and P=0.08, respectively). All but six patients are currently on no
      medication and have resumed all activities without any limitation. These long
      term results confirm that allogeneic BMT is the only curative approach for CML
      patients and should be offered to all patients with a suitable donor as soon
      after diagnosis as possible.

PMID- 11840138
TI  - Allogeneic CD34+ -selected peripheral stem cell transplantation from parental
      donors in children with non-malignant diseases.
AB  - Allogeneic peripheral stem cell transplantation in six children with non
      malignant hematologic or metabolic diseases which are eventually fatal was
      carried out with parental donors. Given three to five HLA mismatches, all grafts
      underwent CD34+ cell selection as graft-versus-host prophylaxis. The patients
      received median doses of 16.7 x 10(6) CD34+ cells/kg and 1.2 x 10(4) CD3+
      cells/kg. All transplants engrafted. Neutrophils >0.5/nl were reached on day 11
      (9-19) and platelets >50/nl on day 13 (10-25). Acute GVHD responding to steriods
      occured in three of six patients; it was restricted to the skin and overall did
      not exceed grade I. Two patients died of viral infections and four are alive with
      stable blood counts for 13, 15, 25 and 26 months. For children with non-malignant
      diseases which will eventually be fatal and which can be cured or ameliorated by
      allogeneic BMT, CD34+-selected stem cell transplants from mismatched or even
      haploidentical parents can be used if no other suitable donor is available. With
      high CD34+ cell doses and low CD3+ cell numbers, engraftment and avoidance of
      acute GVHD can be expected. Infections after transplantation remain the primary
      threat to survival.

PMID- 11840139
TI  - Late onset of invasive aspergillus infection in bone marrow transplant patients
      at a university hospital.
AB  - Despite new antifungal treatment strategies, invasive aspergillosis (IA) remains
      a principal cause of infectious mortality after bone marrow transplantation
      (BMT). We reviewed the medical records of 93 allogeneic and 149 autologous
      transplant recipients during a 20 month period, with attention to cases of proven
      or probable IA. No autologous transplant recipient developed IA, whereas IA was
      seen in 15.1% of allogeneic recipients (including two of five patients with a
      prior history of IA despite prophylaxis), for an overall incidence of 5.8%. The
      median time to occurrence was 92 days post transplant, with no de novo cases
      developing prior to engraftment. Survival 100 days from diagnosis was 29%. Risk
      factors for the development of IA included > or = 21 days of corticosteroid
      therapy of >or= 1mg/kg/day and post-transplant cytomegalovirus (CMV) infection.
      These two risk factors were statistically linked. Our data illustrate a shift
      toward a later occurrence of post-transplant IA, suggesting a need for close,
      prolonged surveillance in the outpatient environment. The contributory role of
      protracted corticosteroid use is also highlighted. These data have important
      implications in an era of alternate donor transplants and more intense
      immunosuppression. Established strategies implementing newer, less toxic
      antifungal agents as prophylaxis in high-risk patients are needed.

PMID- 11840140
TI  - A prospective study of Epstein-Barr virus load in 85 hematopoietic stem cell
      transplants.
AB  - EBV viral load (EBV-VL) in PBMC was prospectively determined by semi-quantitative
      PCR in 85 stem cell transplants (40 genoidentical, 45 non-genoidentical) in order
      to characterize the kinetics of EBV-VL and to assess the ability of this measure
      to predict the development of EBV-induced lymphoproliferative disease (EBV-LPD).
      PCR was performed prior to and after transplantation. An EBV-VL >300
      copies/microg DNA was chosen as the threshold for risk of developing an EBV-LPD.
      Two hundred and fifty-eight EBV-VL measures were evaluable. Five patients (5.9%)
      developed an EBV-LPD. All had an elevated EBV DNA peak level before EBV-LPD.
      Fifteen out of 80 recipients (18.7%) without EBV-LPD had EBV levels over 300
      copies/microg DNA at least once during the follow-up. Overall, the manifestation
      of at least one EBV-VL over 300 copies/microg DNA during the entire follow-up
      demonstrated a sensitivity, specificity, positive and negative predictive value
      for the diagnosis of EBV-LPD of 100%, 81%, 25% and 100%, respectively. In
      patients without EBV-LPD, HLA incompatibility, grade > or = II acute GVHD and use
      of an unmanipulated graft were significantly associated with an EBV-VL >300
      copies/microg DNA. This strategy appears sensitive for the diagnosis of EBV-LPD
      but its positive predictive value has to be improved in order to guide pre
      emptive therapy.

PMID- 11840141
TI  - Intracranial hemorrhage following bone marrow transplantation: an autopsy study
      of 58 patients.
AB  - Autopsy files of 180 patients were reviewed, who died after BMT between July 1987
      and June 1998 and 58 (32.2%) cases, who had experienced intracranial hemorrhage
      (ICH) were selected. Age, sex, underlying disease, preparatory regimens,
      immunoprophylaxis, chronic and acute GVHD, survival of the patients and
      localization and size of hemorrhages were evaluated. There were 33 males and 25
      females, with a mean age of 23.4 years. The main underlying disorders for which
      BMT was performed included SAA (n = 21), CML (n = 13) and AML (n = 10). Forty
      patients were found to have intraparenchymal hemorrhage, 35 had subarachnoid
      hemorrhage and eight patients had subdural hemorrhage. In 16 cases the CNS
      hemorrhage was so extensive that it was considered to be the main cause of death.
      There was no significant statistical difference concerning sex (P = 0.217), age
      (P = 0.296), underlying disease (P= 0.352), preparatory regimens (P = 0.07),
      immunoprophylaxis (P = 0.914), chronic and acute graft-versus-host disease (P =
      0.107 and P = 0.631, respectively) and survival (P = 0.701) when comparing
      patients with or without ICH. However, the number of cases in which the CNS was
      defined as the main cause of death was higher among patients with ICH than in
      patients without ICH (n = 16 vs 15) (P = 0.011). We conclude that ICH is common
      and has a significant mortality rate following BMT.

PMID- 11840142
TI  - Recovery of bone mass and normalization of bone turnover in long-term survivors
      of allogeneic bone marrow transplantation.
AB  - Osteoporotic fractures are potential long-term complications of bone marrow
      transplantation (BMT). We previously reported that bone mineral density (BMD) of
      patients undergoing allogeneic BMT decreased by 6% to 9% during the first 6
      months after BMT and that bone turnover rate was still increased 1 year after
      BMT. BMT patients do not need lifelong immunosuppressive treatment, which should
      offer favorable circumstances for the recovery of BMD. Thus, 27 (14 women, 13
      men) of 29 long-term survivors of our previous study were invited to a follow-up
      study at a median of 75 months after BMT. From 12 months after BMT the BMD of the
      lumbar spine had increased by 2.4% (P = 0.002). The respective changes in femoral
      sites were +4.1% in the femoral neck (P = 0.087), 4.0% in the trochanter (P =
      0.095), +4.7% in Ward's triangle (P = 0.072) and +1.4% in the total hip (P =
      0.23). The markers of bone formation, serum osteocalcin and type I procollagen
      aminoterminal propeptide (PINP) had returned to control levels, but out of the
      markers of bone resorption the mean level of serum type I carboxyterminal
      telopeptide (ICTP) was 41% higher (P = 0.0001) and that of urinary type I
      collagen N-terminal telopeptide/creatinine (NTx) 41% lower (P = 0.0002) in
      patients than in controls. The mean serum 25-hydroxyvitamin D [25(OH)D] was 33%
      lower in patients (P = 0.0002), most of whom had hypovitaminosis D [serum 25(OH)D
      < or = 37 nmol/l]. Except for two, males had serum testosterone level lower than
      before BMT and four men had hypogonadism. In conclusion, in long-term survivors
      of allogeneic BMT BMD recovers and bone turnover state normalizes as compared to
      the situation 1 year after BMT. More attention should be paid to the vitamin D
      status of all recipients and to possible hypogonadism of male patients.

PMID- 11840143
TI  - Translation and validation of the Functional Assessment of Cancer Therapy-Bone
      Marrow Transplant (FACT-BMT) Version 4 quality of life instrument into
      traditional Chinese.
AB  - The need for a culturally sensitive instrument to assess quality of life (QOL) of
      patients in international oncology clinical trials has been well documented. This
      study was designed to evaluate the psychometric properties of the traditional
      Chinese translation (TCHI) of the Functional Assessment of Cancer Therapy-Bone
      Marrow Transplant (FACT-BMT) Version 4. The FACT-BMT consists of the FACT-General
      and treatment-specific concerns of bone marrow transplantation. The Chinese
      translation follows the standard Functional Assessment of Chronic Illness Therapy
      (FACIT) translation methodology. Bilingual teams from the United States and Hong
      Kong reviewed the translation to develop a provisional TCHI FACT-BMT, which was
      then pre-tested by interviewing 20 native Chinese-speaking BMT patients in Hong
      Kong. The pre-test results indicated good content coverage and overall
      comprehensibility. A refined translation, taking into account patient comments,
      was validated by 134 BMT patients in Hong Kong. The results indicated the high
      internal consistency of the TCHI FACT-BMT scales, with Cronbach's alpha
      coefficients ranging from 0.71 (emotional well-being) to 0.92 (FACT-BMT total).
      The FACT-BMT also demonstrated good construct validity when correlated with SF-36
      Health Survey scales. The QOL of Chinese BMT patients can now be evaluated using
      a well-validated international QOL instrument in their own language.

PMID- 11840144
TI  - Evaluation of mixed hematopoietic chimerism in pediatric patients with leukemia
      after allogeneic stem cell transplantation by quantitative PCR analysis of
      variable number of tandem repeat and testis determination gene.
AB  - In order to monitor the clinical outcome of pediatric patients with leukemia
      following allogeneic hematopoietic transplantation, tests of variable number of
      tandem repeat (VNTR) and sex determination by quantitative polymerase chain
      reaction (PCR) were performed. PCR results combined with the blast counts from 21
      leukemia patients were analyzed. Complete chimerism (100% donor cells) was found
      in 15 cases with remission, and incomplete chimerism in six cases with relapse.
      In the majority of cases, complete chimerism was always associated with no
      detectable blasts, while blasts were often detected in association with
      incomplete chimerism. There is significant correlation (P<0.0001) between the
      percentage of donor DNA and blast percentage in these patients. Early detection
      of incomplete chimerism may therefore predict a poor prognosis. In one patient
      (case 15), a differing percentage of donor DNA was observed between samples of
      bone marrow and peripheral blood collected on the same day. This may be due to
      the fact that allogeneic stem cells proliferate at different rates depending on
      their environment (bone marrow or peripheral blood). In addition, 100% donor
      cells found in the peripheral blood may not reflect the number of cells in the
      bone marrow. In case 17, asynchronous engraftment of donor cells was present
      between the white and red blood cell lineages, indicating that the degree of
      chimerism may not be the same in all cell lineages. At the time of this report,
      the significance of this observation is unknown and needs further investigation.

PMID- 11840145
TI  - Technique for PBSC harvesting in children of weight under 10 kg.
AB  - Peripheral blood stem cell (PBSC) harvesting in the smallest children (weight <10
      kg) using separators is complicated by specific problems. The volume of the
      separation set exceeds 25% of the total blood volume and the vascular access is
      generally not sufficient. Therefore, a simple manual technique for PBSC
      harvesting was developed. Three children (6-9 kg), with newly diagnosed tumours
      were scheduled to be treated with three to six sequential courses of high-dose
      chemotherapy, each followed by PBSC support. PBSC harvests were started after
      mobilization using cyclophosphamide and G-CSF when the peripheral blood CD34+
      cell count exceeded 50/microl. About 50 ml of blood was drawn from a venous
      catheter, injected into a transfer bag containing ACD-A, and centrifuged. The
      buffy coat obtained was pooled in a collection bag, remaining plasma and
      erythrocytes were immediately reinfused and a subsequent cycle started. From
      three to 13 cycles were performed in 1-3 days and 18.0-32.2 x 10(6) CD34+cells/kg
      were collected. We did not detect any bacterial contamination or any notable
      complications. Fifteen PBSC reinfusions have been performed to date, each with
      rapid engraftment taking between 7 and 13 days. Patients are in very good PR (18
      months from diagnosis) or in CR (6 and 8 months). We can conclude that this
      procedure is feasible and safe.

PMID- 11840146
TI  - Eradication of residual bcr-abl-positive clones by inducing graft-versus-host
      disease after allogeneic stem cell transplantation in patients with Philadelphia
      chromosome-positive acute lymphoblastic leukemia.
AB  - Persistence of bcr-abl transcripts after marrow grafting is thought to convey a
      high risk for relapse in patients with Philadelphia chromosome (Ph)-positive
      acute lymphoblastic leukemia (ALL). Donor leukocyte infusion (DLI) is closely
      associated with development of graft-versus-host disease (GVHD) and has well
      defined activity against relapsed chronic myelogenous leukemia (CML) but not ALL.
      We report two patients with Ph-positive ALL who remained bcr-abl positive by
      reverse transcriptase polymerase chain reaction (RT-PCR) after marrow grafting.
      Residual bcr-abl transcripts in both patients were eliminated following acute
      GVHD, which was induced by either DLI or rapid reduction of immunosuppression.
      Both patients have continued in complete molecular remission for 18 months and 8
      months following transplantation, respectively. Our observation suggests that
      induction of GVHD may eliminate minimal residual disease, thereby preventing
      leukemia relapse in patients transplanted for Ph-positive ALL.

PMID- 11840147
TI  - Nonmyeloablative allogeneic bone marrow transplantation for orbital granulocytic
      sarcoma associated with t(8;21)(q22;q22) in acute myeloid leukemia.
AB  - We report a nonmyeloablative allogeneic bone marrow transplant (allo-BMT) from an
      HLA-matched unrelated donor in a case of acute myeloid leukemia (AML), M2 with
      t(8;21)(q22;q22) and the presence of orbital granulocytic sarcoma (GS), who had
      residual tumor after conventional chemotherapy. The course of BMT was well
      tolerated, with no major procedure-related toxicity. The residual orbital GS
      regressed completely 4 months after BMT. She is currently 19 months post BMT,
      disease-free. To our knowledge, this is the first reported pediatric patient with
      AML, GS and t(8;21)(q22;q22) who received a nonmyeloablative allo-BMT.

PMID- 11840148
TI  - Nonmyeloablative allogeneic peripheral blood stem cell transplantation for
      multifocal extramedullary plasmacytomas progressing after autologous
      transplantation.
AB  - Multifocal extramedullary plasmacytomas (EMP) are an uncommon manifestation of
      plasma cell malignancies. We report two patients with multiple EMP who developed
      rapidly progressive and ultimately fatal disease shortly after undergoing
      nonmyeloablative, matched-related donor allogeneic peripheral blood stem cell
      transplantation (PBSCT). We have not observed a similar course in patients
      transplanted for multiple myeloma without extramedullary manifestations and
      hypothesize that the intense immunosuppression associated with the fludarabine,
      busulfan and anti-thymocyte globulin conditioning regimen may have contributed to
      rapid disease progression in the two EMP patients. Our observations support the
      assertion that extramedullary disease is a marker for an aggressive, refractory
      plasma cell malignancy and suggest that patients should be treated intensively
      from the time of diagnosis. The utility of a graft-versus-tumor effect and the
      role of nonmyeloablative allogeneic PBSCT is yet to be defined in patients with
      extramedullary plasma cell malignancies, but it is logical to consider using it
      at the time of minimal residual disease rather than at disease relapse or
      progression. Nevertheless, we recommend circumspection in the administration of
      highly immunosuppressive conditioning regimens to patients with refractory EMP
      and encourage further clinical research in this area.

PMID- 11840149
TI  - Successful allogeneic hematopoietic stem cell transplantation (HSCT) for
      Shwachman-Diamond syndrome.
AB  - Shwachman-Diamond syndrome (SDS) is a rare genetic disorder characterized by
      pancreatic insufficiency, short stature, skeletal abnormalities and bone marrow
      dysfunction. Patients with SDS have varying degrees of marrow aplasia, which can
      be severe or progress to leukemic transformation. While allogeneic hematopoietic
      stem cell transplantation (HSCT) can be curative for the hematologic disturbances
      of SDS, a recent review of the literature reveals few survivors. Poor outcome
      with HSCT is often related to excessive cardiac and other organ toxicity from
      transplant preparative therapy. We describe two young children with SDS who
      developed aplastic anemia and subsequently underwent successful allografting
      using a non-cardiotoxic conditioning regimen. Case 1 received marrow from an HLA
      identical sibling while case 2 received partially matched umbilical cord blood
      from an unrelated donor. Both patients are presently alive and well with
      sustained donor engraftment and excellent hematopoietic function at 36 and 22
      months post-HSCT.

PMID- 11840150
TI  - Engraftment syndrome: a common cause for rash and fever following autologous
      hematopoietic stem cell transplantation for multiple sclerosis.
AB  - Autologous hematopoietic stem cell transplantation (HSCT) is currently being
      evaluated as a therapy for patients with progressive multiple sclerosis (MS) at
      risk of debilitating neurological impairment. While preliminary results from a
      few studies have been reported, little is known about toxicities or outcome of
      HSCT for MS. We report a relatively frequent triad of non-infectious fever, rash
      and fatigue or lassitude that may also be associated with pruritus, pulmonary
      symptoms, and eosinophilia and frequently occurs around engraftment. This
      syndrome occurred in 26% of our series of patients (5/19) undergoing HSCT for
      multiple sclerosis. The engraftment syndrome is usually self-limited but may
      require intervention with systemic corticosteroids.

PMID- 11840151
TI  - Resolution of chronic idiopathic thrombocytopenia purpura following syngeneic
      peripheral blood progenitor transplant.
AB  - Idiopathic thrombocytopenia purpura (ITP) is an acquired disease of children and
      adults characterized by a low platelet count, an essentially normal bone marrow,
      and absence of evidence for other disease. We report the use of syngeneic
      peripheral blood progenitor transplantation (PBPT) in a 19-year-old male with
      chronic refractory ITP since the age of 5. Engraftment was successful and has
      resulted in resolution of his disease. We conclude that syngeneic PBPT is a
      potentially curative option for refractory ITP.

PMID- 11840152
TI  - Apoptosis contributes to cyclophosphamide-induced cardiomyopathy.

PMID- 11840153
TI  - Autologous stem cell transplantation in follicular non-Hodgkin's lymphoma.
AB  - The failure of conventional chemotherapy to improve overall survival rates in
      follicular non-Hodgkin's lymphoma (NHL) has led to the development of alternative
      treatment regimens. One such regimen is high-dose chemotherapy (HDT) with
      autologous stem cell transplantation (ASCT). In ASCT stem cells, harvested
      predominantly from peripheral blood, are used to repopulate the haemopoietic
      system after high-dose chemotherapy. Comparison of failure-free survival rates
      following ASCT, with those previously obtained with conventional chemotherapy,
      suggests a benefit for ASCT in patients who have previously responded to
      chemotherapy. Other factors that adversely influence the outcome of ASCT include
      large tumour burden and bcl-2 overexpression. Although ASCT in follicular NHL can
      prolong the period of remission, relapse is still common and can be caused either
      by contamination of the stem cell harvest with tumour cells, or regrowth of
      residual malignant cells not eradicated by the high-dose chemotherapy. Several
      strategies have been developed to reduce the rate of relapse, including in vitro
      purging of the stem cell product to remove tumour cells and using allogenic stem
      cells from HLA-matched donors with no history of malignant disease. While both
      these methods may have some benefit, they also have limitations. In vitro purging
      is labour intensive, costly and, as yet, the effect on relapse is unclear.
      Allogenic stem cell transplants have been associated with a reduced risk of
      relapse, but this is offset by increased transplant-related mortality. The most
      promising strategy to reduce the rate of relapse following ASCT is in vivo
      purging using rituximab, a monoclonal antibody to CD20. Rituximab mobilises
      mechanisms to kill lymphoma cells, and causes a rapid depletion of B cells from
      peripheral blood. Rituximab has demonstrated good efficacy as monotherapy in
      patients with both aggressive and indolent lymphoma and has shown very high
      response rates (>95%) when used in combination with HDT.

PMID- 11840154
TI  - In vivo purging and relapse prevention following ASCT.
AB  - The combination of high-dose chemotherapy and autologous stem cell
      transplantation (ASCT) is a potentially curative therapy for patients with
      relapsed chemosensitive non-Hodgkin's lymphoma (NHL) and is increasingly being
      considered as a first-line treatment for NHL patients with poor prognosis or poor
      outcomes from chemotherapy. However, there is a degree of relapse following the
      latter which is associated with high levels of tumour cell contamination of the
      stem cells and/or the presence of residual malignant cells in the host following
      chemotherapy. Reducing the rate of relapse can be achieved by pre-transplant
      purging of the stem cell graft followed by post-transplant maintenance to
      minimise residual disease. Various methods of in vitro purging have been shown to
      reduce, but not eliminate, the level of stem cell contamination and invariably
      result in a reduced harvest. To date, this has been reflected in disappointing
      outcomes for the patient. In contrast, in vivo purging with rituximab during the
      process of stem cell mobilisation and collection does not adversely affect the
      yield or function of stem cells and shows a significant improvement in the level
      of tumour cell contamination as measured by bcl-2 clearance. The relapse
      potential from residual malignant cells in the host can be addressed by a
      programme of post-transplant rituximab maintenance therapy. In one study 17
      patients with follicular lymphoma who underwent ASCT with in vivo rituximab
      purged stem cells, followed by rituximab maintenance, have all remained in
      complete response at a median follow-up of 12.4 months. The optimum in vivo
      rituximab purging protocol and the precise effect in terms of overall and disease
      free survival are currently being evaluated but appear to present an attractive
      first-line alternative for NHL patients with poor prognosis or poor outcomes
      following chemotherapy.

PMID- 11840155
TI  - Rituximab: enhancing stem cell transplantation in mantle cell lymphoma.
AB  - Mantle cell lymphoma (MCL) responds poorly to standard chemotherapy regimens used
      in non-Hodgkin's lymphoma. As a result, a combination of high-dose chemotherapy
      (HDT) with autologous stem cell transplantation (ASCT) is being investigated in
      patients with MCL. So far, however, there is no evidence for long-term remission 
      - believed, in part, to be due to contamination of the transfusion product with
      residual cancer cells. Many ex-vivo purging methods have been developed to remove
      tumour cells, but these are complicated, time-consuming and expensive. This study
      describes an in vivo purging method using rituximab to produce a tumour-free stem
      cell product for re-infusion following HDT. The regimen is split into a purging
      phase and a myeloablative phase, which together consist of four-step high-dose
      sequential chemotherapy (sHDT) and six infusions of rituximab immunotherapy. The
      sHDT comprises cyclophosphamide, cytosine arabinoside, melphalan and mitoxantrone
      plus melphalan. There are two separate stem cell harvests and three reinfusions.
      In a pilot study 28 patients with untreated MCL received standard chemotherapy
      followed by sHDT with rituximab in vivo purging. Preliminary results indicate
      that in PCR analyses of leukaphereses from 20 assessable patients, 100% lymphoma
      negative harvests were achieved following in vivo purging. PCR analyses of the
      bone marrow following the four-step high-dose regimen with purging and
      transplantation showed that all patients achieved molecular remission. After a
      median follow-up of 22 months (range 10-42 months), two patients had died while
      26 were alive and disease free. This method allows efficient in vivo purging in
      the context of an effective chemotherapy regimen and may have a role as first
      line therapy in MCL patients who respond poorly to standard treatment.

PMID- 11840156
TI  - Bcl-2 clearance: optimising outcomes in follicular non-Hodgkin's lymphoma.
AB  - The long median survival time of patients with follicular non-Hodgkin's lymphoma
      (NHL), means that the efficacy of new treatments are difficult to assess in the
      short term. Bcl-2 is an inhibitor of apoptosis and overexpression of the bcl-2
      gene in the blood or bone marrow is a feature in up to 85% of patients with
      follicular NHL. Levels of bcl-2(+) cells in the peripheral blood or bone marrow
      therefore are a useful measure of disease status in such patients and can be
      detected by polymerase chain reaction (PCR). Complete bcl-2 clearance from the
      bone marrow (molecular remission) following autologous stem cell transplant
      (ASCT) for follicular NHL is considered to be an important prognostic factor for
      disease-free survival. Tumour cell contamination of the stem cell grafts used in
      ASCT is commonly associated with relapse. This can be addressed by purging the
      stem cell harvest prior to transplantation. Various methods of in vitro purging
      after stem cell collection have been shown to reduce the level of contamination
      but yield is invariably reduced and grafts remain bcl-2 positive. However, in
      vivo purging with rituximab during the process of collection has been used to
      obtain bcl-2-negative stem cell harvests without compromising the yield.
      Rituximab is a monoclonal antibody licensed for treatment of relapsed and
      refractory low-grade or follicular NHL. Rituximab targets the CD20 antigen, which
      is found on cells of the B cell lineage. When used for in vivo purging it
      depletes the peripheral blood of CD20-positive cells and prevents contamination
      by lymphoma cells. Molecular remission, as measured by bone-marrow bcl-2
      clearance, has been achieved in 7/7 patients with follicular NHL at 1 year after
      treatment with ASCT using rituximab as an 'in vivopurse', followed by rituximab
      maintenance. Early clinical outcomes are also encouraging.

PMID- 11840157
TI  - A conserved tetrapeptide motif: potentiating apoptosis through IAP-binding.

PMID- 11840158
TI  - Genomic plasticity in cell death susceptibility.

PMID- 11840159
TI  - Mammalian target of rapamycin (mTOR): pro- and anti-apoptotic.

PMID- 11840160
TI  - The death of a T-cell: expression of the CD95 ligand.

PMID- 11840161
TI  - Macrophages are involved in DNA degradation of apoptotic cells in murine thymus
      after administration of hydrocortisone.
AB  - In the present study, we undertook kinetic analyses of DNA degradation and acid
      DNase activity in murine thymus after administration of hydrocortisone.
      Hydrocortisone induced apoptosis in thymocytes, and a large number of cortical
      thymocytes became TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP
      biotin nick end labelling)-positive (TUNEL+). F4/80+ macrophages infiltrated
      through the cortico-medullay junction into the cortical region, and thereafter
      engulfed apoptotic cells in the cortex of thymus. The distribution of acid DNase
      active cells appeared to be similar to that of F4/80+ macrophages. Eighteen hours
      after the injection, although the foci of apoptotic cells were situated within
      massively distended F4/80+ macrophages, oligonucleosomal DNA fragments on an
      agarose gel were undetectable. Our results showed that macrophages were involved
      in the disappearance of oligonucleosomal DNA fragments in apoptotic thymocytes.
      Taken together, macrophages play a role in the hydrolysis of DNA in apoptotic
      cells upon their phagocytosis of the dead cells.

PMID- 11840162
TI  - Induction of apoptotic death in cells via Bad gene expression by infectious
      pancreatic necrosis virus infection.
AB  - A Bcl-2 related family member, Bad, promotes cell death, and its function is
      regulated by phosphorylation. In this study, we show how the IPNV elicits the
      induction of Bad gene expression and promotes host apoptotic death. Anti-IPNV-E1S
      polyclonal and anti-VP3 monoclonal antibodies are used to neutralize the virus
      that blocks the prime death signal via the virus receptor. In the viability
      assay, each antibody could also enhance cell viability during IPNV infection. We
      tested tyrosine kinase inhibitors on IPNV-infected cells in order to assess their
      effect on blocking the death signal. With 100 microg/ml genistein treatment, Bad
      like gene expression was blocked, either by rescuing the IPNV-infected CHSE-214
      cells or by blocking internucleosomal DNA cleavage; but the tyrphostin group did
      not block Bad expression. For CHSE-214 cells, treatment with the protein
      synthesis-inhibitor, cycloheximide (1microg/ml), blocked new protein synthesis
      via activated tyrosine kinase during IPNV infection. We found that Bad protein
      expression could be blocked, and apoptotic death prevented. Together, these
      results demonstrate that the IPNV exerts up-regulation of a pro-apoptotic death
      gene (Bad), the expression of which serves to trigger apoptotic cell death. Our
      data also suggests that the IPNV induces apoptotic death via a viral receptor
      which triggers death effector Bad gene expression, possibly through a tyrosine
      kinase-dependent pathway.

PMID- 11840163
TI  - Formation of noncanonical high molecular weight caspase-3 and -6 complexes and
      activation of caspase-12 during serum starvation induced apoptosis in AKR-2B
      mouse fibroblasts.
AB  - Apoptosis is mainly brought about by the activation of caspases, a protease
      family with unique substrate selectivity. In mammals, different complexes like
      the DISC complex or the apoptosome complexes have been delineated leading to the
      cleavage and thus activation of the executioner caspases. Although caspase-3 is
      the main executioner caspase in apoptosis induced by serum starvation in AKR-2B
      fibroblasts as demonstrated by affinity labeling with YVK(-bio)D.aomk and partial
      purification of cytosolic extracts by high performance ion exchange
      chromatography, its activation is apparently caused by a noncanonical pathway:
      (1) Expression of CrmA, an inhibitor of caspase-8, failed to suppress apoptosis;
      (2) There was no formation of high molecular weight complexes of Apaf-1
      indicative for its activation. Furthermore no cleavage of caspase-9 was observed.
      But surprisingly, gelfiltration experiments revealed the distribution of caspase
      3 and -6 into differently sized high molecular weight complexes during apoptosis.
      Though the apparent molecular weights of the complexes containing caspase-3 (600
      kD for apoptosome and 250 kD for microapoptosome) are in accordance with recently
      published data, the activity profiles differ strikingly. In AKR-2B cells caspase
      3 is mainly recovered as uncomplexed enzyme and in much lower levels in the
      apoptosomes. Remarkably, the 600 kD and 250 kD complexes containing activated
      caspase-3 were devoid of Apaf-1 and cytochrome c. In addition a new 450 kD
      complex containing activated caspase-6 was found that is clearly separated from
      the caspase-3 containing complexes. Furthermore, we disclose for the first time
      the activation of caspase-12 in response to serum starvation. Activated caspase
      12 is detectable as non-complexed free enzyme in the cytosol.

PMID- 11840164
TI  - c-FLIP efficiently rescues TRAF-2-/- cells from TNF-induced apoptosis.
AB  - For the past 20 years, it has been known that preparations of Tumor Necrosis
      Factor alpha (TNF) fail to induce apoptosis due to cytoprotective responses that
      render cells resistant to its cytotoxic activity. Here we show that TRAF-2-/-
      embryonic fibroblasts express reduced levels of the anti-apoptotic molecule c
      FLIP due to extensive degradation of the protein. Reconstitution of TRAF-2-/- EF
      with c-FLIP is sufficient for resistance to TNF toxicity. Our results strengthen
      the role of c-FLIP in protecting cells from the cytotoxic effect of TNF and have
      implication for the treatment of inflammatory and proliferative disorders.

PMID- 11840165
TI  - Dynamics of expression of apoptosis-regulatory proteins Bid, Bcl-2, Bcl-X, Bax
      and Bak during development of murine nervous system.
AB  - We have used immunohistochemistry and immunoblotting to examine the expression of
      Bid and four other Bcl-2 family proteins (Bcl-2, Bcl-X, Bax and Bak) in the
      developing and adult murine central nervous system (CNS). Bid protein is
      widespread in embryonic and postnatal brain, and its expression is maintained at
      a high level late into the adulthood. Bid is expressed both in the germ disc,
      early neural tube, proliferating stem cells of ventricular zones, and in
      postmitotic, differentiated neurons of the developing central and peripheral
      nervous system. As the differentiation proceeds, the neurons express higher
      levels of Bid than the stem cells of the paraventricular zone. Both in embryonic
      and postnatal life, Bid protein is present in the most vital regions of brain,
      such as the limbic system, basal ganglia, mesencephalic tectum, Purkinje cells in
      cerebellum, and the ventral columns of spinal cord. The p15 cleaved form of Bid
      was detectable in the brain specimens at fetal stages of development, consistent
      with caspase-mediated activation of this pro-apoptotic Bcl-2 family protein.
      Among the Bcl-2 family proteins only Bid and Bcl-XL continue to be expressed at
      high levels in the adult brain.

PMID- 11840166
TI  - An ARL1 mutation affected autophagic cell death in yeast, causing a defect in
      central vacuole formation.
AB  - When the cdc28 strain of Saccharomyces cerevisiae is incubated at restrictive
      temperatures, the yeasts digest themselves in 7 days by activating autophagic
      machinery. In parallel, the cell-proliferative activity decreases progressively
      after about 48 h. We have previously referred to this phenomenon as autophagic
      death. In the present study, we isolated and characterized a recessive mutant
      strain, dlp2, which delays the progression toward autophagic death. The cdc28
      dlp2 cells contain many small vesicles instead of the large central vacuoles that
      are usually found in parental cdc28 cells. We showed that the dlp2 phenotype
      results from the presence of a single mutation in the gene ARL1 (ADP-ribosylation
      factor-like protein 1). Morphological and biochemical analyses of cdc28 dlp2
      suggested that a defect in central vacuole formation is caused by aberrant
      membrane trafficking, although the protein-sorting to vacuoles is not affected.
      After a shift to a restrictive temperature, the components of the cytoplasm and
      nucleus of cdc28 dlp2 were condensed, with an accompanying formation of vesicles
      in the periphery (epiplasm) of the cells rather than an activation of the
      autophagic machinery. Introducing this ARL1 mutation into the normal ARL1 locus
      of the wild-type W303 strain again inhibited the progression of apoptotic cell
      death due to a defect in vacuole formation, which in this case was induced by the
      proapoptotic protein Bax. Thus, the ARL1 gene plays an important role in the
      formation of central vacuoles and in the progression of programmed cell death
      induced by cell-cycle arrest or Bax. These results suggested the presence of a
      programmed-cell death machinery in yeast that is similar to that related to the
      Type II cell death of mammalian cells characterized by autophagocytosis.

PMID- 11840167
TI  - Maintenance of ATP favours apoptosis over necrosis triggered by benzamide
      riboside.
AB  - A new synthetic drug, benzamide riboside (BR) exhibited strong oncolytic activity
      against leukemic cells in the 5-10 microM range. Higher BR-concentrations (20
      microM) predominantly induced necrosis which correlated with DNA strand breaks
      and subsequent depletion of ATP- and dATP levels. Replenishment of the ATP pool
      by addition of adenosine prevented necrosis and favoured apoptosis. This effect
      was not a pecularity of BR-treatment, but was reproduced with high concentrations
      of all trans-retinoic acid (120 microM) and cyanide (20 mM). Glucose was also
      capable to suppress necrosis and to favour apoptosis of HL-60 cells, which had
      been treated with necrotic doses of BR and cyanide. Apoptosis eliminates unwanted
      cells without affecting the microenvironment, whereas necrosis causes severe
      inflammation of surrounding tissues due to spillage of cell fluids into the peri
      cellular space. Thus, the monitoring and maintenance of cellular energy pools
      during therapeutic drug treatment may help to minimize nonspecific side effects
      and to improve attempted drug effects.

PMID- 11840169
TI  - Mitochondrial involvement in tracheary element programmed cell death.
AB  - The mitochondria pathway is regarded as a central component of some types of
      programmed cell death (PCD) in animal cells where specific signals cause the
      release of cytochrome c from mitochondria to trigger a proteolytic cascade
      involving caspases. However, plant cells lack canonical caspases, therefore a
      role for the mitochondria in programmed cell death in plant cells is not obvious.
      Using plant cells which terminally differentiate, we provide evidence supporting
      the involvement of mitochondria in PCD, however the release of cytochrome c is
      insufficient to trigger the PCD. Prior to execution of cellular autolysis
      initiated by the rupture of the large central vacuole to release sequestered
      hydrolases, mitochondria adopt a definable morphology, the inner membrane
      depolarizes prior to death, and cytochrome c is released from mitochondria.
      However, PCD can be blocked despite translocation of cytochrome c. These results
      suggest a role for the mitochondria in this PCD but do not support the current
      animal model for a causative role of cytochrome c in triggering PCD.

PMID- 11840168
TI  - Propionibacteria induce apoptosis of colorectal carcinoma cells via short-chain
      fatty acids acting on mitochondria.
AB  - The genus Propionibacterium is composed of dairy and cutaneous bacteria which
      produce short-chain fatty acids (SCFA), mainly propionate and acetate, by
      fermentation. Here, we show that P. acidipropionici and freudenreichii, two
      species which can survive in the human intestine, can kill two human colorectal
      carcinoma cell lines by apoptosis. Propionate and acetate were identified as the
      major cytotoxic components secreted by the bacteria. Bacterial culture
      supernatants as well as pure SCFA induced typical signs of apoptosis including a
      loss of mitochondrial transmembrane potential, the generation of reactive oxygen
      species, caspase-3 processing, and nuclear chromatin condensation. The
      oncoprotein Bcl-2, which is known to prevent apoptosis via mitochondrial effects,
      and the cytomegalovirus-encoded protein vMIA, which inhibits apoptosis and
      interacts with the mitochondrial adenine nucleotide translocator (ANT), both
      inhibited cell death induced by propionibacterial SCFA, suggesting that
      mitochondria and ANT are involved in the cell death pathway. Accordingly,
      propionate and acetate induced mitochondrial swelling when added to purified
      mitochondria in vitro. Moreover, they specifically permeabi-lize proteoliposomes
      containing ANT, indicating that ANT can be a critical target in SCFA-induced
      apoptosis. We suggest that propionibacteria could constitute probiotics efficient
      in digestive cancer prophylaxis via their ability to produce apoptosis-inducing
      SCFA.

PMID- 11840170
TI  - Cell death induced by a caspase-cleaved transmembrane fragment of the Alzheimer
      amyloid precursor protein.
AB  - The Alzheimer amyloid precursor protein (APP) is a transmembrane protein whose
      abnormal processing is associated with the pathogenesis of Alzheimer's disease.
      Activated caspases cleave APP and generate its carboxyl-terminally truncated
      fragment (APPdeltaC31). We have previously reported that overexpression of wild
      type APP induces caspase-3 activation and apoptosis in postmitotic neurons. We
      now report that APPdeltaC31 potentially plays pathophysiological roles in
      neuronal death. Adenovirus-mediated overexpression of wild-type APP695 induced
      activation of caspase-3 and accumulation of APPdeltaC31 in postmitotic neurons
      derived from human NT2 embryonal carcinoma cells, whereas an APP mutant lacking
      the Abeta(1-20) region induced neither caspase-3 activation nor APPdeltaC31
      generation. Inhibition of caspase-3 suppressed the generation of APPdeltaC31 in
      APP-overexpressing neurons. Forced expression of APPdeltaC31 induced apoptotic
      changes of neurons and non-neuronal cells, but failed to activate caspase-3. The
      cytotoxicity of APPdeltaC31 was also dependent on the Abeta(1-20) region. These
      results suggest that accumulation of wild-type APP activates neuronal caspase-3
      to generate APPdeltaC31 that mediates caspase-3-independent cell death.

PMID- 11840171
TI  - Apoptosis coincident with the differentiation of skeletal myoblasts is delayed by
      caspase 3 inhibition and abrogated by MEK-independent constitutive Ras signaling.
AB  - We demonstrate that during 23A2 skeletal myoblast differentiation, between 30-35%
      of the population apoptose. Both differentiation and apoptosis are controlled by
      the variables of cell density and time and these variables are inversely related.
      In response to conditions that permit both differentiation and apoptosis of
      parental 23A2 myoblasts, myoblasts rendered differentiation-defective by
      constitutive Ras signaling (A2:H-Ras myoblasts) do not apoptose. This is not
      merely a consequence of their differentiation-defective phenotype since myoblasts
      rendered differentiation-defective by expression of E1A (A2:E1A myoblasts) still
      apoptose. Although signaling through MEK is important to the survival of
      proliferating parental 23A2 myoblasts, constitutive signaling through MEK is not
      responsible for the survival of A2:H-Ras myoblasts. Finally, we demonstrate that
      caspase 3 is activated and that pharmacological inhibition of caspase 3 activity
      delays apoptosis without affecting differentiation. Abrogating apoptosis without
      affecting differentiation could be a useful approach to improve the efficacy of
      myoblast transfer in the treatment of muscular dystrophies.

PMID- 11840172
TI  - Deformation-induced endothelin B receptor-mediated smooth muscle cell apoptosis
      is matrix-dependent.
AB  - To maintain normal blood flow, pressure overload in both arteries and veins
      requires a structural adaptation of the vessel wall (remodelling) that involves
      smooth muscle cell (SMC) hypertrophy and/or hyperplasia. Due to its potent
      vasoconstrictor and growth-promoting effects, endothelin-1 (ET-1) is a likely
      candidate to initiate and/or promote remodelling in blood vessels exposed to a
      chronic increase in blood pressure. To test this hypothesis, isolated segments of
      the rabbit carotid artery and jugular vein were perfused at different levels of
      intraluminal pressure. In both types of segments, pressure overload (160 and 20
      mmHg, respectively) resulted in an increase in endothelial prepro-ET-1 and SMC
      endothelin B receptor (ETB-R) expression. Moreover, in pressurised segments from
      the carotid artery an ETB-R antagonist-sensitive increase in SMC apoptosis in the
      media was observed, while in the vein medial SMC started to proliferate. Isolated
      SMC from these rabbit blood vessels as well as from the aorta and vena cava of
      the rat, when cultured on a collagen or laminin matrix, uniformly revealed an ETB
      R-mediated increase in apoptosis upon exposure to mechanical deformation plus
      exogenous ET-1 (10 nmol/L). However, when grown on a fibronectin matrix, the
      cultured SMC did not respond with an increase in apoptosis under otherwise
      identical experimental conditions. These findings suggest that deformation
      induced activation of the endothelin system in the vessel wall not only plays a
      crucial role in remodelling, but that the structural components of the vessel
      wall, in particular the cell-matrix interaction, determine how SMC respond
      phenotypically to these changes in gene expression.

PMID- 11840174
TI  - Cereal grains and coronary heart disease.
AB  - Cereal grains and their products provide around 30% of total energy intake in
      British adults, (much more than any of the other major food groups). Coronary
      heart disease (CHD) is the largest single cause of death in Britain and many
      other Western countries. This review examines the question whether there is a
      relation between cereal consumption and CHD. Several of the nutrients in cereals
      have known potential for reducing risk factors for CHD: the linoleic acid, fibre,
      vitamin E, selenium and folate. Cereals also contain phytoestrogens of the lignan
      family and several phenolic acids with antioxidant properties. Processing
      generally reduces the content of these nutrients and bioprotective substances.
      Although cereals at the farm gate are very low in salt, processed cereal foods,
      eg bread and some breakfast cereals, are high-salt foods and thus could
      contribute to raising blood pressure. Human experiments have clearly shown that
      oat fibre tends to lower plasma total and LDL cholesterol but wheat fibre does
      not. Rice bran and barley may also lower cholesterol but most people do not eat
      enough barley to have an effect. Cereal foods with low glycaemic index such as
      pasta and oats are beneficial for people with diabetes and might lower plasma
      lipids. Between 1996 and 2001 an accumulation of five very large cohort studies
      in the USA, Finland and Norway have all reported that subjects consuming
      relatively large amounts of whole grain cereals have significantly lower rates of
      CHD. This confirms an earlier report from a small British cohort. The protective
      effect does not seem to be due to cholesterol-lowering. While cohort studies have
      shown this consistent protective effect of whole grain cereals, there has been
      (only one) randomised controlled secondary prevention trial of advice to eat more
      cereal fibre. In this there was no reduction of the rate of reinfarction. The
      trial had some weaknesses, eg there were eight different diets, compliance was
      not checked objectively, and duration was for only 2 y. It appears valid to make
      health claims (as now permitted by the US FDA) that whole grain cereal foods and
      oat meal or bran may reduce the risk of CHD.

PMID- 11840175
TI  - Body composition changes in patients with anorexia nervosa after complete weight
      recovery.
AB  - OBJECTIVE: To assess body composition changes occurring in female anorectic
      patients after complete weight recovery. DESIGN: Longitudinal study. SUBJECTS: :
      Ten female patients with anorexia nervosa (age at baseline: 19.7+/-5.8 y) were
      studied both when undernourished (body mass index, BMI 14.8+/-1.3 kg/ m(2)) and
      after the achievement of a BMI >18.5 kg/m(2). The control group comprised 18 well
      nourished women (age 20.1+/-4.4 y; BMI 19.0-23.0 kg/ m(2)). INTERVENTIONS: Fat
      mass and fat-free mass were determined by dual-energy X-ray absorptiometry.
      Skinfold thicknesses and circumferences were also measured. Arm muscle area and
      arm fat area were calculated by standard formulas. RESULTS: The undernourished
      patients had lower fat-free mass, fat mass, skinfold thicknesses and
      circumferences. After refeeding, fat mass represented 25-71% (mean 56%) of the
      mass regained, this percentage being directly related to the extent of weight
      gain. The increases in skinfolds and circumferences depended upon the site
      considered and were correlated to a various extent with those in weight or BMI.
      Skinfolds at biceps and abdominal sites and the waist-to-hip ratio remained
      significantly higher, whereas arm muscle circumference was significantly lower,
      in the refed group than in the control one. CONCLUSION: The percentage of fat in
      the weight regained by refed female anorectic patients was directly related to
      the extent of body mass increase. Refed anorectic patients appear to
      preferentially regain fat in the abdominal and triceps regions. Abnormalities in
      skinfolds (at biceps and abdominal sites), arm muscle area and waist-to-hip ratio
      still persist in refed anorectic patients in comparison to control healthy
      controls.

PMID- 11840176
TI  - Validation of a food frequency questionnaire for nutritional calcium intake
      assessment in Italian women.
AB  - OBJECTIVE: To evaluate a food frequency questionnaire assessing calcium intake in
      women. DESIGN: : Estimates of calcium intake from the food frequency
      questionnaire were compared with those from 14 day records from 206 Caucasian
      women aged 25-75 y in Siena, Italy. SUBJECTS: Subjects were randomly recruited
      from the residents list of the city of Siena, Italy. Of the 250 initially
      recruited, 39 did not meet the inclusion criteria or failed to complete the diet
      record and five outliers were excluded before the statistical analysis on the
      basis that their diet record was unlikely to represent habitual intake. RESULTS:
      Mean dietary calcium intakes were 829+/-255 (s.d.) mg/day from the questionnaire
      and 818+/-260 (s.d.) mg/day from the diet record. The mean difference in intake
      by the two methods (-11.3+/-116.4 mg/day) did not differ significantly from zero.
      Specificity in classifying women consuming less than 800 mg/day calcium was
      86.6%, and sensibility in classifying women consuming more than 800 mg/day
      calcium was 89.4%. CONCLUSIONS: The food frequency questionnaire could be used in
      epidemiological studies to assess calcium intake in young to elderly women. The
      specificity in identifying low calcium intake subjects makes it useful also as an
      educational tool in diet counselling and for prescribing calcium supplementation.

PMID- 11840177
TI  - Reported adverse food reactions overestimate true food allergy in the community.
AB  - OBJECTIVE: To determine the extent to which perceived adverse food reactions were
      associated with IgE mediated food allergy, as defined by skin prick testing
      (SPT). DESIGN: A cohort epidemiological study. Participants underwent SPT to five
      common food allergens (cow's milk, peanut mix, egg white, shrimp and whole grain
      wheat mix) and were asked whether they had ever suffered any food
      'illness/trouble', and if so to list such food(s). A positive SPT was defined as
      wheal diameter of > or =3 mm. Cohen's kappa (kappa) was used to assess the
      agreement between SPT and self-reported reactions to food(s) which contained the
      allergen of interest. SETTING: Randomly selected adults who took part in the
      follow-up of the European Community Respiratory Health Survey (ECRHS) in 1998.
      SUBJECTS: The subjects were 457 adults aged 26-50 y. RESULTS: Fifty-eight (13%)
      adults were sensitised to at least one food allergen whilst 99 adults (22%)
      reported illness to food(s) nearly always. However, only seven subjects who
      reported illness to a food also had a positive SPT to the same food. The
      prevalence of adverse food reactions associated with IgE mediated allergy in the
      adult general population would be less than 1.5% (7/457). The agreement between
      SPT and self-reported illness to food(s) was poor for cow's milk (kappa=0) and
      wheat (kappa=0), slight for shrimp (kappa=0.16) and egg white (kappa=0.09) and
      fair for peanut mix (kappa=0.37). CONCLUSIONS: There was little agreement between
      self-reported perceived illness to food(s) known to contain the food allergen of
      interest, and positive SPT, suggesting that most reactions are not due to IgE
      mediated food allergy.

PMID- 11840178
TI  - Lipid, protein and carbohydrate intake in relation to body mass index.
AB  - OBJECTIVE: To examine whether the same amount of energy intake has different
      consequences on body mass index (BMI), depending on the source of energy from
      specific macronutrients. DESIGN: Cross-sectional study, in the context of the
      European Prospective Investigation into Cancer and nutrition (EPIC). SETTING:
      Communities all over Greece. SUBJECTS: A total of 27 862 apparently healthy
      volunteers, men and women, ages 25-82 y. INTERVENTIONS: None. METHODS: Dietary
      information was collected through an interviewer-administered semi-quantitative
      food frequency questionnaire. In the context of a cross-sectional analysis, we
      calculated changes of BMI per increments of energy intake from protein,
      carbohydrates, saturated, polyunsaturated and monounsaturated lipids and ethanol,
      controlling for mutual confounding and other confounders, among all participants,
      and after exclusion of under-reporters and/or those on a diet. RESULTS: Protein
      intake was positively associated with BMI. The association was evident when
      nutrients were not mutually adjusted for and increased after mutual adjustment
      among nutrients (beta=0.80 kg/m(2) per 418.4 kJ or 100 kcal increment, 95%
      confidence interval 0.55-1.06 for men, and beta=1.59, 95% CI 1.30-1.88 for
      women), as well as after exclusion of under-reporters and/or those on a diet. The
      effects of other macronutrients were less substantial or consistent. CONCLUSIONS:
      There is evidence indicating that protein intake is conducive to obesity.
      Moreover, our data suggest that neither saturated or monounsaturated lipids nor
      carbohydrates are likely to play a major role in increasing BMI over and beyond
      that indicated by their energy content.

PMID- 11840179
TI  - Vitamin A, retinol binding protein and lipids in type 1 diabetes mellitus.
AB  - OBJECTIVE: A case-control study was conducted to evaluate the effects of type 1
      diabetes mellitus (IDDM) on plasma levels of vitamin A (retinol) and serum levels
      of retinol-binding protein (RBP) and their relationship with the atherogenic
      indicators. SUBJECTS: A total of 47 randomised IDDM children were recruited from
      those treated at the Endocrinology Unit of the University Hospital of Granada
      (Spain). They were matched for age and sex with 16 healthy children. METHODS: The
      following parameters were measured in all patients: serum concentrations of total
      cholesterol, triglycerides, high (HDL, spectrophotometry), very low (VLDL) and
      low (LDL) density lipoprotein cholesterol (Friedewald's formula); serum levels of
      RBP (kinetic nephelometry); plasma vitamin A and glycosilated haemoglobin (HbA1c;
      high performance chromatography). RESULTS: Higher RBP concentrations in IDDM
      children (P=0.05), lower retinol levels (P=0.05) and lower vitamin A/cholesterol
      ratio (P=0.02) than in the control group were found; no differences in the
      atherogenic indicators were observed. There was a correlation between RBP and
      vitamin A (P=0.0001). Relationships between retinol, RBP and atherogenic
      indicators were demonstrated in the IDDM group (A-LDLc/HDLc (P=0.01); A
      (VLDL+LDL)c/HDLc (P=0.007); RBP-LDLc/HDLc (P=0.05); RBP-(VLDL+LDL)c/HDLc
      (P=0.02)), and an inverse relationship was found between the vitamin A/TG ratio
      and HbA1c (P=0.004). The children with HbA1c>8% showed increased atherogenic
      indicators and lower vitamin A/CHOL and vitamin A/TG ratios than those with good
      control of the illness. CONCLUSIONS: The IDDM children with poor metabolic
      control face a higher atherogenic risk and vitamin A 'relative deficiency' risk
      than those with good metabolic control of their illness. Relationships between
      retinol and RBP with atherogenic indicators were found. The results suggest that
      vitamin A therapeutic supplements in IDDM children may reduce or prevent
      atherogenic risk.

PMID- 11840180
TI  - Vitamin D deficiency: a concern in premenopausal Bangladeshi women of two socio
      economic groups in rural and urban region.
AB  - OBJECTIVE: The study was designed to evaluate the vitamin D status in women of
      different physiological status of two socio-economic groups in Bangladesh.
      DESIGN: A cross-sectional study, using serum 25-hydroxyvitamin D (25-OHD),
      calcium, phosphorus and alkaline phosphatase activity. SETTING: Two regions of
      Bangladesh. The Dhaka city area and west region of Nandail (Betagair Union),
      Mymensingh. SUBJECTS: Representative subjects of two groups (low socio-economic
      group=group L, n=99; and high socio-economic group=group H, n=90) of Bangladeshi
      women aged 16-40 y. About 87% of the subjects were housewives and the rest, 13%,
      were distributed among other different professions. Each group comprised of three
      sub-groups (non-pregnant non-lactating=1, pregnant=2, and lactating=3). RESULTS:
      The influence of socio-economic status and physiological status on serum 25-OHD
      concentration (P=0.038, P=0.015, respectively), serum calcium concentration
      (P<0.001, P<0.001, respectively) and alkaline phosphatase activity (P<0.001,
      P<0.001, respectively) were observed. The distribution of serum 25-OHD
      concentration in both groups was shifted overall toward the lower limit of the
      normal range. Seventeen percent of women in group L and 12% of women in group H
      had serum 25-OHD concentration <25 nmol/l. Hypovitaminosis D (serum 25-OHD
      concentration < or = 37.5 nmol/l) was observed in 50% of subjects in group L and
      38% of subjects in group H, respectively. The prevalence of hypovitaminosis was
      higher in lactating subjects of the groups L and H (63 and 46%, respectively)
      than in the other sub-groups in the same group. CONCLUSIONS: The results of the
      study suggested that women in Bangladesh were at risk of hypovitaminosis D and
      lactation was an additional risk factor in low income groups. The situation may
      increase the risk of bone loss.

PMID- 11840181
TI  - Does the association between smoking status and selected healthy foods depend on
      gender? A population-based study of 54 417 middle-aged Danes.
AB  - OBJECTIVE: Smoking serves different functions for men and women. Thus, we wanted
      to investigate the association between smoking behaviour and intakes of selected
      healthy foods in men and women with special focus on differences and similarities
      between the two genders. DESIGN: In 1993-1997, a random sample of 80 996 men and
      79 729 women aged 50-64 y was invited to participate in the study 'Diet, Cancer
      and Health'. In all, 27 179 men and 29 876 women attended a health examination
      and completed a 192-item food-frequency questionnaire (FFQ). The association
      between smoking status and low, median and high intakes of selected foods was
      examined among 25 821 men and 28 596 women. SETTING: The greater Copenhagen and
      Aarhus area, Denmark. RESULTS: For both men and women, smoking status group was
      associated with diet, such that increasing level of smoking status ranging from
      never smokers over ex-smokers to currently heavy smokers was associated with a
      lower intake of the healthy foods: fresh fruit, cooked vegetables, raw
      vegetables/salad, and olive oil. For wine, increasing level of smoking status
      category was associated with a higher fraction of abstainers and heavy drinkers.
      The difference between the extreme smoking status categories was larger than the
      difference between men and women within smoking status categories such that never
      smoking men in general had a higher intake of healthy foods than heavy smoking
      women. Correction for age, educational level, and body mass index (BMI) did not
      affect the results. CONCLUSION: In this middle-aged population, intake of healthy
      foods were associated with smoking behaviour with a dose-response type of
      relationship. The overall pattern was similar for men and women.

PMID- 11840182
TI  - Lipid-lowering effects of a modified butter-fat: a controlled intervention trial
      in healthy men.
AB  - OBJECTIVE: To investigate the lipid-lowering potential of a butter-fat modified
      through manipulations in bovine feeding to increase the unsaturated:saturated
      fatty acid ratio. DESIGN: Double-blind, randomised, cross-over intervention
      trial. SETTING: University of Auckland Human Nutrition Unit, New Zealand.
      SUBJECTS: Twenty healthy, male subjects. INTERVENTION: A residential trial in
      which all foods and beverages were provided during two intervention periods,
      comprising 3 weeks of high unsaturated 'modified' vs. 3 weeks of saturated
      'control' butter feeding separated by a 4 week washout. Diets were of typical
      composition of 39 percentage energy (en%) fat (20 en% butter-fat), 48 en% CHO, 13
      en% protein. RESULTS: There was a significant decrease in both total (P<0.05, 
      7.9%) and LDL-cholesterol (P<0.01, -9.5%) during modified butter feeding. There
      was no significant effect of treatment on a range of other risk factors including
      HDL-cholesterol, triglyceride, apolipoprotein A or B, nonesterified fatty acids
      (NEFA), haemostatic clotting factor VII and fibrinogen or glucose (P>0.05).
      Subjects were maintained in energy balance and there was no significant change in
      body weight during intervention. Butter-fat composition alone differed between
      treatments. CONCLUSIONS: A significant improvement in cardiovascular risk can be
      achieved by moderate changes in dietary fatty acid profile, achieved through a
      common and well accepted food source, butter-fat.

PMID- 11840183
TI  - Effects of dietary fatty acids on the composition and oxidizability of low
      density lipoprotein.
AB  - OBJECTIVE: The objective of this study was to compare the effects of dietary
      monounsaturated fatty acids (MUFA), n-6 and n-3 polyunsaturated fatty acids
      (PUFA) on LDL composition and oxidizability. DESIGN, SETTING AND SUBJECTS: Sixty
      nine healthy young volunteers, students at a nearby college, were included. Six
      subjects withdrew because of intercurrent illness and five withdrew because they
      were unable to comply with the dietary regimen. INTERVENTIONS: The participants
      received a 2-week wash-in diet rich in saturated fatty acids (SFA) followed by
      diets rich in refined olive oil, rapeseed oil or sunflower oil for 4 weeks.
      Intakes of vitamin E and other antioxidants did not differ significantly between
      the diets. RESULTS: At the end of the study, LDL oxidizability was lowest in the
      olive oil group (lag time: 72.6 min), intermediate in the rapeseed oil group
      (68.2 min) and highest in the sunflower oil group (60.4 min, P<0.05 for
      comparison of all three groups). Despite wide variations in SFA intake, the SFA
      content of LDL was not statistically different between the four diets (25.8-28.5%
      of LDL fatty acids). By contrast, the PUFA (43.5%-60.5% of LDL fatty acids) and
      MUFA content of LDL (13.7-29.1% of LDL fatty acids) showed a wider variability
      dependent on diet. CONCLUSIONS: Enrichment of LDL with MUFA reduces LDL
      susceptibility to oxidation. As seen on the rapeseed oil diet this effect is
      independent of a displacement of higher unsaturated fatty acids from LDL.
      Evidence from this diet also suggests that highly unsaturated n-3 fatty acids in
      moderate amounts do not increase LDL oxidizability when provided in the context
      of a diet rich in MUFA.

PMID- 11840184
TI  - Effect of tamarind ingestion on fluoride excretion in humans.
AB  - OBJECTIVE: To evaluate the effect of tamarind (Tamarindus indicus) ingestion on
      excretion of fluoride in school children. DESIGN: Randomized, diet-control study.
      SUBJECT: Twenty healthy boys were included and 18 of them completed the study.
      INTERVENTIONS: Each subject consumed 10 g tamarind daily with lunch for 18 days
      at the social welfare boys' hostel. The nutrient composition of the daily diet
      was constant throughout the experimental period. RESULTS: Tamarind intake led to
      significant increase (P<0.001) in the excretion of fluoride in 24 h urine (4.8+/
      0.22 mg/day) as compared to excretion on control diet (3.5+/-0.22 mg/day).
      However, excretion of magnesium and zinc decreased significantly (7.11+/-1.48 mg
      of Mg and 252.88+/-12.84 microg of Zn per day on tamarind diet as compared to
      23.39+/-3.68 mg of Mg and 331.78+/-35.31 microg Zn per day on control diet).
      Excretion of calcium and phosphorous were not significantly different while
      creatinine excretion decreased with tamarind intake (225.66+/-81 mg
      creatinine/day with tamarind and 294.5+/-78.76 mg creatinine/day without
      tamarind). CONCLUSION: Tamarind intake is likely to help in delaying progression
      of fluorosis by enhancing urinary excretion of fluoride.

PMID- 11840185
TI  - Appetite sensations and eating behaviors to complete fasting in obese and non
      obese individuals.
AB  - OBJECTIVE: To investigate the response of appetite sensations and eating
      behaviors to fasting in obese and non-obese individuals. DESIGN: Prospective
      study on inpatients enrolled in weight loss program including fasting at the
      obesity clinic, an oriental medical center in Seoul, Korea. SUBJECTS AND
      MEASUREMENTS: For seven obese (body mass index BMI> or =30) and 11 non-obese
      (BMI<30) patients, the modified visual analog scale (VAS) was administered three
      times per day throughout 9 days of complete fasting. Three-Factor Eating
      Questionnaire (TEEQ) was administered before and 18 days after the complete
      fasting period. RESULTS: After treatment, average weight losses were 7.4 kg (3.0
      BMI) for the obese group and 6.7 kg (2.6 BMI) for the non-obese. TFEQ scales did
      not differ by weight status at both before and after treatments. Eighteen days
      after the fasting, an increase of restraint of eating was found only for the non
      obese. There was a decrease of disinhibition of eating regardless of weight
      status. During fasting, desire to eat, hunger and prospective consumption
      decreased for the non-obese, while these appetite sensations tended to increase
      slightly for the obese. CONCLUSIONS: BMI, independent of dieting status, appeared
      to be related to appetite sensations except for satiety during fasting, but not
      before and 18 days after fasting.

PMID- 11840186
TI  - Mutation and linkage disequilibrium in human mtDNA.

PMID- 11840188
TI  - Cryptic subtelomeric translocation t(2;16)(q37;q24) segregating in a family with
      unexplained stillbirths and a dysmorphic, slightly retarded child.
AB  - We here describe a submicroscopic translocation affecting the subtelomeric
      regions of chromosomes 2q and 16q, and segregating in a family with stillbirths,
      early pregnancy losses, and two dysmorphic and slightly retarded babies. FISH
      analysis showed a 46,XY,der(2)t(2;16)(q37.3;q24.3) in the propositus, and a
      balanced t(2;16) in his mother, her conceptus and maternal grandfather. FISH with
      YACs and BACs made it possible to map the 2q37 breakpoint precisely between the
      regions covered by y952E1 and y746H1, and the 16q breakpoint between the regions
      encompassed by bA 309g16 and bA 533d19. The contribution of 2q37.3 monosomy and
      16q24.3 trisomy to the proband's phenotype is compared with that in reported
      patients with similar imbalances of either chromosome.

PMID- 11840189
TI  - Evidence from skewed X inactivation for trisomy mosaicism in Silver-Russell
      syndrome.
AB  - The finding of maternal uniparental disomy for chromosome 7 (matUPD7) in
      approximately 7% of Silver-Russell syndrome (SRS) cases has lead to the
      assumption that imprinted gene(s) on chromosome 7 are responsible for at least
      some cases. However, the observation in a familial case that both maternal and
      paternal inheritance of proximal 7p results in an SRS-like phenotype suggests
      that the causative genes may not be imprinted, and that an extra copy of genes
      within this region cause SRS. As all cases of complete matUPD7 could have arisen
      by trisomy rescue, it is possible that undetected trisomy 7 mosaicism contributes
      towards the phenotype of SRS, and that the matUPD7 seen in some cases is a
      consequence of trisomy rescue. Previous studies in cases of trisomy rescue for a
      number of autosomes have shown a strong association with skewed X inactivation in
      diploid tissues. Thus, we hypothesised that if trisomy mosaicism was involved in
      SRS, the frequency of skewed X inactivation should be increased in a population
      of non-matUPD7 SRS patients. Consistent with this hypothesis, results showed a
      significant increase in the frequency of completely skewed X inactivation in SRS
      patients (three of 29) when compared to controls (three of 270), suggesting the
      possible presence of undetected trisomy 7 in SRS patients and/or their placentas.

PMID- 11840190
TI  - Genomic organisation of the approximately 1.5 Mb Smith-Magenis syndrome critical
      interval: transcription map, genomic contig, and candidate gene analysis.
AB  - Smith-Magenis syndrome (SMS) is a multiple congenital anomalies/mental
      retardation syndrome associated with an interstitial deletion of chromosome 17
      involving band p11.2. SMS is hypothesised to be a contiguous gene syndrome in
      which the phenotype arises from the haploinsufficiency of multiple, functionally
      unrelated genes in close physical proximity, although the true molecular basis of
      SMS is not yet known. In this study, we have generated the first overlapping and
      contiguous transcription map of the SMS critical interval, linking the proximal
      17p11.2 region near the SMS-REPM and the distal region near D17S740 in a minimum
      tiling path of 16 BACs and two PACs. Additional clones provide greater coverage
      throughout the critical region. Not including the repetitive sequences that flank
      the critical interval, the map is comprised of 13 known genes, 14 ESTs, and six
      genomic markers, and is a synthesis of Southern hybridisation and polymerase
      chain reaction data from gene and marker localisation to BACs and PACs and
      database sequence analysis from the human genome project high-throughput draft
      sequence. In order to identify possible candidate genes, we performed sequence
      analysis and determined the tissue expression pattern analysis of 10 novel ESTs
      that are deleted in all SMS patients. We also present a detailed review of six
      promising candidate genes that map to the SMS critical region.

PMID- 11840191
TI  - Spectrum of CLCN1 mutations in patients with myotonia congenita in Northern
      Scandinavia.
AB  - Myotonia congenita is a non-dystrophic muscle disorder affecting the excitability
      of the skeletal muscle membrane. It can be inherited either as an autosomal
      dominant (Thomsen's myotonia) or an autosomal recessive (Becker's myotonia)
      trait. Both types are characterised by myotonia (muscle stiffness) and muscular
      hypertrophy, and are caused by mutations in the muscle chloride channel gene,
      CLCN1. At least 50 different CLCN1 mutations have been described worldwide, but
      in many studies only about half of the patients showed mutations in CLCN1.
      Limitations in the mutation detection methods and genetic heterogeneity might be
      explanations. In the current study, we sequenced the entire CLCN1 gene in 15
      Northern Norwegian and three Northern Swedish MC families. Our data show a high
      prevalence of myotonia congenita in Northern Norway similar to Northern Finland,
      but with a much higher degree of mutation heterogeneity. In total, eight
      different mutations and three polymorphisms (T87T, D718D, and P727L) were
      detected. Three mutations (F287S, A331T, and 2284+5C>T) were novel while the
      others (IVS1+3A>T, 979G>A, F413C, A531V, and R894X) have been reported
      previously. The mutations F413C, A531V, and R894X predominated in our patient
      material. Compound heterozygosity for A531V/R894X was the predominant genotype.
      In two probands, three mutations cosegregated with myotonia. No CLCN1 mutations
      were identified in two families. Our data support the presence of genetic
      heterogeneity and additional modifying factors in myotonia congenita.

PMID- 11840192
TI  - Low incidence of UPD in spontaneous abortions beyond the 5th gestational week.
AB  - Approximately 15-20% of all clinically recognised pregnancies abort, most
      commonly between 8-12 gestational weeks. While the majority of early pregnancy
      losses is attributed to cytogenetic abnormalities, the aetiology of approximately
      40% of early abortions remains unclear. To determine additional factors causing
      spontaneous abortions we retrospectively searched for uniparental disomies (UPD)
      in 77 cytogenetically normal diploid spontaneous abortions. In all cases an
      unbalanced chromosome anomaly was ruled out by cytogenetic investigation of
      chorionic/amniotic membranes and/or chorionic villi. For UPD screening
      microsatellite analyses were performed on DNA of abortion specimens and parental
      blood using highly polymorphic markers showing UPD in two cases. The distribution
      of markers analysed indicated maternal heterodisomy for chromosome 9 (UPhD(9)mat)
      in case 1 and paternal isodisomy for chromosome 21 (UPiD(21)pat) in case 2. The
      originating mechanism suggested was monosomy complementation in UPiD(21)pat and
      trisomy rescue in UPhD(9)mat. In the case of UPhD(9)mat purulent chorioamnionitis
      was noted and a distinctly growth retarded embryo of 3 cm crown-rump length
      showing no gross external malformations. Histological analysis in the case of
      UPiD(21)pat suggested a primary anlage defect. Our results indicate that less
      than 3% of genetically unexplained pregnancy wastage is associated with total
      chromosome UPD. UPD may contribute to anlage defects of human conception.
      Chromosome aneuploidy correction can occur in very early cleavage stages. More
      research, however, ought to be performed into placental mosaicism to further
      clarify timing and mechanisms involved in foetal UPD.

PMID- 11840193
TI  - The level of the mitochondrial mutation A3243G decreases upon ageing in
      epithelial cells from individuals with diabetes and deafness.
AB  - We have in a longitudinal study determined the proportion of the mitochondrial
      A3243G mutation in DNA obtained from cervical cell samples collected from three
      individuals affected with mitochondrial diabetes and hearing loss during a period
      of up to 18 years. Using the minisequencing method we were able to sensitively
      determine the proportion between mutant and normal mitochondrial DNA. Our results
      demonstrate a constant decrease in the levels of the pathogenic mutation in
      mitotic tissues of affected individuals with time.

PMID- 11840194
TI  - NEDD4L on human chromosome 18q21 has multiple forms of transcripts and is a
      homologue of the mouse Nedd4-2 gene.
AB  - The validation of full-length cDNA represents a crucial step in gene
      identification and subsequent functional analysis. In searching for candidate
      genes for bipolar disorder on chromosome 18q21, a novel gene homologous to NEDD4
      (Neural precursor cells expressed developmentally down-regulated) was identified
      using exon trapping and cDNA cloning. This novel gene is termed NEDD4L (Human
      Gene Nomenclature Committee symbol). Typical NEDD4 orthologues that contain a C2
      (Ca(2+)/lipid-binding) and a HECT (Homologous to the E6-AP Carboxyl Terminus)
      ubiquitin-protein ligase domain, and multiple WW domains have been shown to
      regulate the epithelial sodium channel (ENaC). In mice, Nedd4 has two distinct
      isoforms termed Nedd4-1 that belongs to the typical NEDD4 class, and Nedd4-2 that
      is homologous to Nedd4-1 but lacks the C2 domain. NEDD4L contains the WW and HECT
      domains seen in the NEDD4 gene family, but lacks the C2 domain in the N-terminus.
      BLAST database search showed that the deduced polypeptide of NEDD4L has 97 and
      62% sequence identity to mouse Nedd4-2 and human NEDD4, respectively. Multiple
      forms of transcripts of NEDD4L have been isolated, which differ in transcription
      start and termination sites together with the presence or absence of an
      alternative spliced exon. Northern blot analysis showed a 3.4 kb mRNA species was
      specifically expressed in heart and skeletal muscle, while a 3.2 kb band and/or
      an additional 3.6 kb band is seen in other tissues tested. Striking homology of
      NEDD4L to mouse Nedd4-2 suggests it is the human homologue of mouse Nedd4-2. Its
      position in a region of linkage for autosomal dominant orthostatic hypotensive
      disorder and its potential role in regulating ENaC make NEDD4L a candidate gene
      for this disorder.

PMID- 11840195
TI  - Molecular characterisation of glutamate dehydrogenase gene defects in Japanese
      patients with congenital hyperinsulinism/hyperammonaemia.
AB  - Congenital hyperinsulinism and hyperammonaemia (CHH) is caused by dysregulation
      of glutamate dehydrogenase (GDH). We characterised the GDH gene in two Japanese
      patients with CHH. Patient 1 showed late-onset and mild hypoglycaemic episodes
      and mild hyperammonaemia, compared with patient 2. In GDH activity of
      lymphoblasts, patient 1 showed twofold higher basal GDH activity than control
      subjects and mild insensitivity for GTP inhibition. Patient 2 showed severe
      insensitivity for GTP inhibition, and similar allosteric stimulation by ADP in
      the controls. Genetic studies identified heterozygous and de novo L413V and G446D
      mutations in patients 1 and 2, respectively. COS cell expression study confirmed
      that both mutations were disease-causing gene. The insensitivity for GTP
      inhibition in L413V and G446D was emphasised in COS cell expression system as a
      result of the dosage effect of mutant GDH gene. L413V showed less impairment of
      GDH than G446D based on biochemical and genetic results, which was consistent
      with the clinical phenotype. Based on the structure of bovine GDH, G446D was
      located in GTP binding site of pivot helix and its surroundings, while L413V was
      located in alpha-helix of antenna-like structure. These different locations of
      mutations gave different effects on GDH enzyme. The antenna-like structure plays
      an important role in GDH activity.

PMID- 11840197
TI  - Allergic rhinitis--a total genome-scan for susceptibility genes suggests a locus
      on chromosome 4q24-q27.
AB  - Allergic rhinitis is a common disease of complex inheritance and is characterised
      by mucosal inflammation caused by allergen exposure. The genetics of closely
      related phenotypes such as asthma, atopy and to some extend atopic dermatitis has
      attracted attention in recent years. Genetic reports of allergic rhinitis on the
      contrary have as yet been most sparse. To identify candidate regions holding
      genes for allergic rhinitis we performed a total genome-scan on affected sib-pair
      families. From 100 Danish sib-pair families selected for allergy, families
      containing sib-pairs matching a phenotype definition of both clinical allergic
      rhinitis and confirmed specific allergy were chosen. Thirty-three affected sib
      pair families qualified for the scan that was undertaken using 446 microsatellite
      markers. Non-parametric linkage results were obtained from MAPMAKER/SIBS computer
      program. The study revealed one major candidate region on chromosome 4q24-q27
      (LOD=2.83) and eight minor candidate regions 2q12-q33, 3q13, 4p15-q12, 5q13-q15,
      6p24-p23, 12p13, 22q13, and Xp21 (LOD=1.04-1.63) likely to contain susceptibility
      genes for allergic rhinitis. Our findings did not support a previous report of
      linkage of allergic rhinitis to chromosome 12q14-q24 but they added positive
      evidence to the asthma and atopy candidate regions 2q33 and 6p23. Further
      identification of the specific genes involved in allergic rhinitis will give
      opportunities for improved diagnosis and treatment.

PMID- 11840196
TI  - Genome-wide linkage analysis of Scandinavian affected sib-pairs supports presence
      of susceptibility loci for celiac disease on chromosomes 5 and 11.
AB  - Celiac disease (CD) is a common chronic inflammatory disorder of the small
      intestine with a multifactorial aetiology. HLA is a well-known risk factor, but
      other genetic factors also influence disease susceptibility. To identify the
      genes involved in this disorder, we performed a genome-wide scan on 106 well
      defined Swedish and Norwegian families with at least two affected siblings. We
      investigated familial segregation of 398 microsatellite markers, and utilised non
      parametric linkage analysis. The strongest linkage with disease was found to the
      HLA locus (6p) (P<0.000006). There were eight regions besides HLA with a point
      wise P value below 0.05. Among these eight regions were 11q and 5q, both of which
      have been suggested in several linkage studies of independent celiac disease
      families. We also performed a stratification analysis of families according to
      their HLA genotypes. This resulted in significant differences on chromosome 2q.
      These results indicate that 11q, 5q and possibly also 2q are true susceptibility
      regions in CD.

PMID- 11840198
TI  - Teaching undergraduates about familial breast cancer: comparison of a computer
      assisted learning (CAL) package with a traditional tutorial approach.
AB  - We have developed a computer assisted learning package for teaching clinical
      medical students about familial breast cancer. It explains the principles of
      genetic predisposition to breast cancer, the association with other cancers, the
      principles of family history taking and confirmation, risk assessment and
      possible interventions. Clinical medical students were randomised to either
      conventional teaching or CAL, 48 students attended the evaluation session.
      Students randomised to conventional teaching received a 20 min mini-lecture,
      those randomised to CAL completed the package with technical, but not academic
      support available. At the end of the intervention both groups of students
      completed a short written assessment of acceptability and knowledge and
      understanding of breast cancer genetics. There was no significant difference
      between the CAL and mini-lecture groups in terms of marks or acceptability. Thus
      CAL appears to be an acceptable and effective method of teaching clinical medical
      students about familial breast cancer. Although time consuming to develop, CAL
      can be used in a variety of settings to increase curriculum flexibility. Methods
      of motivating students to complete the CAL, and of providing educational support
      are being explored.

PMID- 11840199
TI  - Mutation detection for exons 2 to 10 of the polycystic kidney disease 1 (PKD1)
      gene by DGGE.
AB  - The PKD1-gene encodes a 14 kb transcript spanning a 50 kb genomic interval. Two
      thirds of the gene is reiterated at another locus on the same chromosome. Using
      Long Range PCR with primers in intron 1 and exon 11, 6.8 kb PKD1 specific
      fragments were generated on genomic DNA. These products were used as templates
      for nested PCR's to screen exons 2-10 by Denaturing Gradient Gel Electrophoresis
      (DGGE). Upon analysis of 36 patients, a total of 11 different sequence variants
      were observed: A nonsense mutation in exon 2, a frameshift mutation in exon 8 and
      furthermore, two amino acid changes, two silent polymorphisms and five intronic
      variants.

PMID- 11840200
TI  - HFE gene mutations analysis in Basque hereditary haemochromatosis patients and
      controls.
AB  - C282Y/C282Y genotype is the prevalent genotype in Hereditary Haemochromatosis
      (HH), however, other genotypes have been associated with the disease. The
      objective of our study was to analyse the frequency of the three main mutations
      of HFE gene in HH patients and controls from the Basque population with
      differential genetic characteristics. Thirty five HH patients and 116 controls
      were screened for C282Y, H63D and S65C mutations using a PCR-RFLP technique. The
      association of HLA-A and-B alleles and HFE mutations was also studied in Basque
      controls. The frequency of C282Y homozygotes in the group of patients was only
      57%. The rest of the patients presented heterogeneous genotypes, including
      compound heterozygotes: 11% of them were C282Y/H63D; and 2.85% were H63D/S65C.
      H63D or S65C heterozygotes had a frequency of 11% and 2.85 respectively and 5.71%
      patients lacked any mutation The high frequency of H63D in the healthy Basque
      population is confirmed in this study. A considerable incidence of S65C is
      observed either in controls and in HH (3%) or in iron overloaded patients. The
      peculiar genetic characteristics of Basques could explain the heterogeneity of
      genotypes in HH patients of this group. Further studies should be carried out to
      confirm these findings although the implication of other genetic or external
      factors in the development of HH is suggested.

PMID- 11840201
TI  - Distribution of the M129V polymorphism of the prion protein gene in a Turkish
      population suggests a high risk for Creutzfeldt-Jakob disease.
AB  - A polymorphism (M129V) at codon 129 of the prion protein gene (PRNP) results in
      either a methionine residue (Met) or a valine residue (Val) and is known to
      determine susceptibility for the development of sporadic or acquired Creutzfeldt
      Jakob disease (CJD). The distributions of M129V genotypes and alleles in various
      general populations have been reported and there are clear differences between
      Western Europeans and East Asians. We analysed the coding sequence of the PRNP
      gene in 100 healthy Turkish subjects to determine whether the distributions of
      the M129V genotypes and alleles or other PRNP gene variants in the Turkish
      population differ from those in other normal populations. Three known
      polymorphisms but no other gene variants were detected in the PRNP coding
      sequence of the Turkish individuals. Genotype frequencies at codon 129 were 57%
      Met/Met, 34% Met/Val and 9% Val/Val, with an allele frequency of 0.740:0.260
      Met:Val. These distributions are considerably different from those reported for
      other normal populations residing in Western Europe and East Asia, except in
      Crete. The higher frequency of 129 Met-homozygotes in Turkey than in Western
      Europe suggests that the Turkish are at greater risk of developing CJD.

PMID- 11840205
TI  - Obesity. Introduction.

PMID- 11840206
TI  - Clinical implications of the ponderostat concept: view from the chair.

PMID- 11840207
TI  - Regulation and the ponderostat.
AB  - Control theory is concerned mainly with the treatment of signals. This article
      takes into account that living beings not only treat information, but they are
      open systems traversed by flows of energy and mass. A block diagram of the
      regulation process is proposed, taking into account this fundamental difference
      between engineered and living systems. This new diagram is used to describe the
      stability of body weight. The ponderostat is hypothesized to work as a regulation
      of blood glucocorticoids with a hypothalamic set-point related to CRH
      concentration.

PMID- 11840208
TI  - Psychobiology of food preferences.
AB  - Investigations with laboratory animals can reveal much about the basic
      psychobiological determinants of food preference and diet-induced overeating.
      When offered a choice of foods, rats typically prefer high-fat and/or high-sugar
      food items over their nutritionally balanced chow diet. In addition, they may
      increase their total energy intake by 20-40% and consequently develop mild to
      moderate obesity. The role of flavor and postingestive nutritional actions on the
      preference for and overconsumption of fat- and sugar-rich foods has been
      questioned. To evaluate flavor and nutritional effects independently, recent
      studies have used self-regulated intragastric feeding paradigms. The results
      indicate that enhancing the flavor of food can significantly increase energy
      intake when nutrient composition is held constant. Similarly, changes in nutrient
      composition (ie fat-carbohydrate ratio) can significantly influence energy intake
      when flavor is held constant. In addition, postingestive nutrient actions can
      significantly alter flavor preferences through a conditioning process as function
      of nutrient type and concentration. Thus, food preferences and overeating result
      from interactions between the orosensory and nutritional properties of food.

PMID- 11840209
TI  - Brain reward circuitry and the regulation of energy balance.
AB  - Reward signals contribute to the regulation of energy balance by influencing
      switching between feeding and competing behaviors. Properties of natural rewards
      are mimicked by electrical stimulation of certain brain regions. The rewarding
      effect produced by stimulating the perifornical region of the hypothalamus is
      modulated by body weight and is attenuated both by leptin and insulin. Research
      is reviewed concerning the dependence of the rewarding effect of perifornical
      stimulation on long-term energy stores and the effects of two neuropeptides
      implicated in the regulation of energy balance, neuropeptide Y and corticotropin
      releasing hormone. It is proposed that the potentiating effect of weight loss on
      perifornical self-stimulation is not tied to an increased propensity to eat or to
      an enhancement of food reward per se, but resembles the influence of long-term
      energy stores on non-ingestive behaviors that defend body weight, such as
      hoarding.

PMID- 11840210
TI  - An adipose-specific control of thermogenesis in body weight regulation.
AB  - Much of our understanding about 'adaptive thermogenesis' as a control system in
      mammalian weight regulation derives from studies of experimental starvation and
      overfeeding, and these have served to characterize its functional role as an
      'attenuator' of energy imbalance. By applying a system-analysis approach in
      evaluating data on the energetics of starvation and refeeding, evidence is
      presented here in support of the hypothesis that there are in fact two distinct
      control systems underlying adaptive thermogenesis. In one of them, the efferent
      limb is primarily under the control of the sympathetic nervous system (SNS),
      whose functional state is dictated by overlapping or interacting signals arising
      from a variety of environmental stresses, including food deprivation, deficiency
      of essential nutrients, excess energy intake and exposure to cold or to
      infections; it is hence referred to as the non-specific control of thermogenesis,
      and is likely to occur primarily in organs/tissues with a high specific metabolic
      rate (eg liver, kidneys, brown fat). The other is independent of the functional
      state of the SNS and is dictated solely by signals arising from the state of
      depletion of the adipose tissue fat stores; it is hence referred to as the
      adipose-specific control of thermogenesis, and is postulated to occur primarily
      in the skeletal muscle. While suppression of this adipose-specific thermogenesis
      during both starvation and refeeding leads to energy conservation, the energy
      spared during refeeding is directed specifically at the replenishment of the fat
      stores, so that it functions as an 'accelerator' of fat recovery. These two
      distinct control systems for adaptive thermogenesis have been incorporated in a
      compartmental model of body weight and body composition regulation. This is used
      to provide a mechanistic explanation as to how, during weight recovery, they can
      operate simultaneously but in opposite directions--with activation of
      thermogenesis under non-specific control being energy-dissipating, while
      suppression of thermogenesis under adipose-specific control being energy
      conserving--and could hence explain the paradox of a high efficiency of fat
      recovery co-existing with an overall state of enhanced thermogenesis and
      hypermetabolism. Elucidating the components of the adipose-specific control of
      thermogenesis (ie its sensors, signals and effector mechanisms) will have
      important implications for our understanding of body composition regulation, and
      hence for the development of more effective strategies in the management of
      cachexia and obesity.

PMID- 11840211
TI  - Endocrine and neuroendocrine signals of energy stores: view from the chair.

PMID- 11840212
TI  - Insulin as an adiposity signal.
AB  - Insulin is now well established as an adiposity signal that acts in the brain to
      influence energy homeostasis. It is secreted in direct proportion to adiposity;
      it enters the brain from the blood, and it interacts with neurons in the ventral
      hypothalamus. Experimental manipulation of brain insulin causes predictable
      changes of food intake and body weight. Because insulin shares many properties
      with other adiposity signals, especially leptin, in this regard, it is important
      to recognize the similarities and differences in the signal each conveys to the
      brain in order to design effective therapeutic approaches to treat pathologies of
      eating and body weight.

PMID- 11840213
TI  - Within-meal gut feedback signaling.
AB  - During a meal, multiple gastrointestinal sites are stimulated by ingested
      nutrients and their digestion products, initiating local gastrointestinal actions
      and producing a variety of potential feedback signals that can contribute to meal
      termination. During ingestion, gastric emptying is rapid, allowing a significant
      portion of ingested nutrients to enter the intestine. Gastric and duodenal vagal
      afferent fibers increase their electrophysiological activity in relation to the
      mechanical presence of ingested nutrients. On reaching the duodenum, nutrients
      also activate vagal chemosensitive elements and stimulate the release of a
      variety of brain gut peptides including cholecystokinin (CCK). CCK also activates
      vagal afferent fibers directly and modifies the response properties of vagal
      mechanosensitive fibers to gastric and duodenal loads. Blocking or eliminating
      these feedback signals results in increased meal size demonstrating their role in
      meal termination.

PMID- 11840214
TI  - Glucagon-like peptide containing pathways in the regulation of feeding behaviour.
AB  - The pre-proglucagon derived peptides, glucagon-like peptide-1 (GLP-1) and
      glucagon-like peptide-2 (GLP-2) are both involved in a wide variety of peripheral
      functions, such as glucose homeostasis, gastric emptying, intestinal growth,
      insulin secretion as well as the regulation of food intake. Pre-proglucagon is
      also found in the brainstem in a small population of nerve cells in the nucleus
      of the solitary tract (NTS) that process the pre-propeptide as in the gut to
      yield GLP-1 and GLP-2. GLP-1 containing nerve fibres and the GLP-1 receptor are
      found predominantly in hypothalamic midline nuclei. GLP-1 given centrally to
      naive rats results in a marked induction of c-Fos protein in the supraoptic
      nucleus, paraventricular nucleus of the hypothalamus (PVN) and central nucleus of
      the amygdala, but only a moderate increase in the arcuate nucleus. The pattern of
      c-Fos activation is compatible with the appetite suppressing effects of GLP-1.
      This anorectic effect of GLP-1 appears to be mediated by the PVN, as direct
      injections of GLP-1 into this nucleus cause anorexia without concomitant taste
      aversion, suggesting a specific action upon neuronal circuits involved in the
      regulation of feeding. Recent experiments have also shown that GLP-1 is
      implicated in mediating signals from the gastrointestinal tract pertaining to
      discomfort and malaise. The distribution of the co-localised peptide, GLP-2,
      displays a perfect overlap with GLP-1 in the CNS with the highest concentration
      in the diffuse ventral part of the dorsomedial nucleus (DMHv). In contrast to the
      widely distributed GLP-1 receptor mRNA, GLP-2 receptor mRNA is exclusively
      expressed in the compact part of the DMH (DMHc). Interestingly, the DMHc is also
      the only nucleus responding to central administration of GLP-2 with a significant
      increase in the number of c-Fos positive cells. When injected into the lateral
      ventricle, GLP-2 has a marked inhibitory effect on feeding. The effect of GLP-2
      on feeding is both behaviourally and pharmacologically specific. Future
      experiments will elucidate whether or not GLP-1 and GLP-2 are involved in the
      long-term or short-term regulation of feeding behaviour and hence have an impact
      on bodyweight.

PMID- 11840215
TI  - Cytokines and feeding.
AB  - Various categories of cytokines participate in the control of feeding, including
      interleukin-1 and -6 and other activators of gp 130, leptin (ob protein),
      interleukin-8 and other chemokines, tumor necrosis factor-alpha, and interferon
      alpha. These feeding-inhibitory cytokines may play a role in the regulation of
      food intake during physiological (eg a role proposed for leptin) and
      pathophysiological (eg proinflammatory cytokines) conditions. Data show that
      various cytokines participate in acute and chronic disease-associated anorexia
      such as during infection, inflammation or malignancy. Food intake suppression
      (reported as anorexia) is also a common central manifestation observed during
      cytokine immunotherapy in humans. The concept of local production of various
      cytokines within specific brain regions in response to peripheral challenges and
      pathophysiological processes has broad implications for the interpretation of
      brain cytokines as mediators or participants in CNS modulation of feeding and
      anorexia.

PMID- 11840216
TI  - Leptin action in the brain: view from the chair.

PMID- 11840217
TI  - The NPY/AgRP neuron and energy homeostasis.
AB  - Kennedy hypothesized nearly 50 y ago that negative feedback regulation of body
      fat stores involves hormones that circulate in proportion to adiposity and enter
      the brain, where they exert inhibitory effects on food intake and energy balance.
      Recent studies implicate leptin and insulin as 'adiposity signals' to the brain
      that promote negative energy balance in two ways: by inhibiting 'anabolic'
      hypothalamic neuronal circuits that stimulate food intake and promote weight
      gain, and by activating 'catabolic' pathways that reduce food intake and body
      weight. Chief among candidate 'anabolic' effector pathways is the NPY/AgRP
      neuron, found only in the hypothalamic arcuate nucleus. These neurons make
      peptides that potently stimulate food intake not only by increasing neuropeptide
      Y (NPY) signaling, but by reducing melanocortin signaling via the release of
      agouti-related peptide (AgRP), an endogenous melanocortin 3/4 receptor
      antagonist. Since NPY/AgRP neurons express receptors for leptin and insulin and
      are inhibited by these hormones, they are activated by a decrease of leptin or
      insulin signaling. Fasting, uncontrolled diabetes, and genetic leptin deficiency
      are examples of conditions in which food intake increases via a mechanism
      hypothesized to involve NPY/AgRP neurons. Data are reviewed which illustrate the
      role of these neurons in adaptive and maladaptive states characterized by
      hyperphagia and weight gain.

PMID- 11840218
TI  - The arcuate nucleus as a conduit for diverse signals relevant to energy
      homeostasis.
AB  - Arcuate nucleus neurons are known to be responsive to a wide array of hormones
      and nutrients, including leptin, insulin, gonadal steroids and glucose. In
      addition to potential transport mechanisms, peripheral substances may access
      these neurons via arcuate cell bodies in and projections to the median eminence,
      a region considered to be a circumventricular organ. The arcuate is a potent site
      of leptin action, probably mediating a component of leptin's effects via arcuate
      neuropeptide Y/agouti-related peptide (NPY/AgRP) and pro-opiomelanocortin (POMC)
      neurons, and implicating this structure in the long-term control of energy
      stores. However, ghrelin, the endogenous ligand of the growth hormone
      secretagogue receptor, may also stimulate feeding and weight gain, in part
      through action on receptors in arcuate NPY neurons. Since ghrelin is secreted by
      the stomach upon content depletion, with a half-life of no more than an hour, the
      arcuate nucleus may also be important in sensing and responding to acute changes
      in nutrients. We have developed a system for recording from arcuate POMC neurons
      using a mouse containing a transgene in which the POMC promoter is driving
      expression of the green fluorescent protein (GFP). In these mice, 99% of the beta
      endorphin positive neurons express GFP, making whole cell patch clamp recordings
      from the sparsely distributed POMC neurons facile. All of the POMC neurons appear
      to be activated by leptin, via two different mechanisms, while approximately 30
      50% of the neurons appear to be inhibited by a gamma-melanocyte stimulating
      hormone (MSH) specific agonist. The latter result suggests that the melanocortin
      3 receptor (MC3-R) may act as an autoinhibitory receptor on some POMC neurons.
      This hypothalamic slice preparation also confirms the responsiveness of arcuate
      POMC neurons to a wide variety of nutrients and hormones. Thus the arcuate
      melanocortin system is best described as a conduit of many diverse signals
      involved in energy homeostasis, with leptin acting tonically to regulate the
      responsiveness of the circuit to a wide variety of hormones and nutrients.

PMID- 11840219
TI  - Glucosensing neurons do more than just sense glucose.
AB  - The brain regulates energy homeostasis by balancing energy intake, expenditure
      and storage. To accomplish this, it has evolved specialized neurons that receive
      and integrate afferent neural and metabolic signals conveying information about
      the energy status of the body. These sensor-integrator-effector neurons are
      located in brain areas involved in homeostatic functions such as the
      hypothalamus, locus coeruleus, basal ganglia, limbic system and nucleus tractus
      solitarius. The ability to sense and regulate glucose metabolism is critical
      because of glucose's primacy as a metabolic substrate for neural function. Most
      neurons use glucose as an energy substrate, but glucosensing neurons also use
      glucose as a signaling molecule to regulate neuronal firing and transmitter
      release. There are two types of glucosensing neurons that either increase
      (glucose responsive, GR) or decrease (glucose sensitive, GS) their firing rate as
      brain glucose levels rise. Little is known about the mechanism by which GS
      neurons sense glucose. However, GR neurons appear to function much like the
      pancreatic beta-cell where glycolysis regulates the activity of an ATP-sensitive
      K(+) (K(ATP)) channel. The K(ATP) channel is composed of four pore-forming units
      (Kir6.2) and four sulfonylurea binding sites (SUR). Glucokinase (GK) appears to
      modulate K(ATP) channel activity via its gatekeeper role in the glycolytic
      production of ATP. Thus, GK may serve as a marker for GR neurons. Neuropeptide Y
      (NPY) and pro-opiomelanocortin (POMC) neurons in the hypothalamic arcuate nucleus
      are critical components of the energy homeostasis pathways in the brain. Both
      express Kir6.2 and GK, as well as leptin receptors. They also receive visceral
      neural and intrinsic neuropeptide and transmitter inputs. Such metabolism-related
      signals can summate upon K(ATP) channel activity which then alters membrane
      potential, neuronal firing rate and peptide/transmitter release. The outputs of
      these neurons are integral components of effector systems which regulate energy
      homeostasis. Thus, arcuate NPY and POMC neurons are probably prototypes of this
      important class of sensor-integrator-effector neurons.

PMID- 11840220
TI  - Interoceptive and integrative contributions of forebrain and brainstem to energy
      balance control.
AB  - An anatomically distributed model of energy balance control contrasts with the
      widely held hypothalamic center model. The distributionist model is recommended
      by the observations that the caudal brainstem contains critical interoceptive,
      integrative and neurochemical mediating functions. A prominent example of
      interoceptive function is sensitivity to the adipose tissue-derived hormone,
      leptin. To complement the well established focus on hypothalamic leptin receptors
      (Ob-Rb), we describe an extensive distribution of Ob-Rb in the brainstem. These
      receptors, moreover, are functionally relevant given the intake suppressive
      effects of fourth-intracerebroventricular (i.c.v) and brainstem intraparenchymal
      (in dorsal vagal complex) delivery. A wide variety of intake relevant peptides
      receptors are found in hypothalamus, but these receptors are also widely
      distributed in the caudal brainstem. As an example of the functional relevance of
      these neurochemical mediators, we describe ingestive effects of ligands for
      melanocortin 3/4 and corticotrophin-releasing hormone receptors obtained with
      brainstem ventricular and parenchymal (dorsal vagal complex and parabrachial
      nucleus) delivery. It is clear that responses obtained from hypothalamic
      treatments can arise independently from stimulation of caudal brainstem
      receptors. We have used the chronic decerebrate preparation to ask whether the
      brainstem contains integrative substrates sufficient to mediate behavioral
      responses to variations in physiological state. The experiments reveal that the
      brainstem is indeed sufficient for the integration of taste and gastrointestinal
      signals that co-determine the size of meals in the short term. Decerebrate rats,
      however, do not respond to food deprivation or to reductions in the number of
      daily feeding opportunities. These results suggest that the brainstem in neural
      isolation from forebrain influence is not sufficient for ingestive response to
      systemic/metabolic signals that affect intake over the long term. The relative
      contribution of brainstem and forebrain substrates to long-term intake and body
      weight control in the neurologically intact animal, remains unclear. The data
      reviewed support a distributed anatomical model of energy balance and recommend
      increased attention to specific responses (behavioral, autonomic and endocrine)
      that are mediated by local (brainstem or forebrain) interoceptive and integrative
      processes, and those requiring bi-directional interactions.

PMID- 11840223
TI  - Sibutramine and blood pressure: a therapeutic dilemma.

PMID- 11840221
TI  - Hypothalamic pathways underlying the endocrine, autonomic, and behavioral effects
      of leptin.
AB  - Leptin affects body weight by decreasing food intake, activating the sympathetic
      nervous system and regulating neuroendocrine function. This type of regulation is
      a hallmark of hypothalamic control, which typically integrates autonomic,
      endocrine and behavioral responses. We have performed a series of experiments
      investigating hypothalamic pathways underlying these actions of leptin. We found
      that leptin activates neurons that coexpress pro-opiomelanocortin (POMC) and
      cocaine- and amphetamine-regulated transcript (CART) mRNA. These neurons
      innervate several sites, including sympathetic preganglionic neurons in the
      spinal cord, neurons in the paraventricular hypothalamic nucleus (PVH), and
      melanin-concentrating hormone and orexin neurons in the lateral hypothalamic area
      (LHA). Following leptin administration, POMC neurons express both Fos and
      suppressor of cytokine signalling-3 (SOCS-3) mRNA. In contrast, leptin induced
      SOCS-3 expression in neuropeptide Y (NPY) neurons but not Fos, suggesting that
      leptin acts differentially on NPY and POMC cells. We also investigated potential
      downstream targets of leptin responsive NPY and POMC neurons by assessing the
      distribution of the melanocortin 4 receptor (MC4-R) mRNA and Y1 and Y5 NPY
      receptor mRNA in chemically defined neurons. We found dense MC4-R mRNA expression
      in several sites including the PVH and LHA. Using dual-label in situ
      hybridization we found that MC4-R mRNA is coexpressed in PVH cells expressing pro
      TRH mRNA. We also found Y1 and Y5 NPY receptor mRNA in the PVH in patterns very
      similar to that of MC4R, suggesting that these receptors may be coexpressed on at
      least some PVH neurons. These results provide a neuroanatomic framework
      explaining the endocrine, autonomic and behavioral effects of leptin.

PMID- 11840224
TI  - Sibutramine is safe and effective for weight loss in obese patients whose
      hypertension is well controlled with angiotensin-converting enzyme inhibitors.
AB  - Sibutramine treatment in obesity results in significantly greater weight
      reduction compared with placebo, although weight loss with sibutramine may be
      accompanied by small but statistically significant mean increases in blood
      pressure (BP). This 52-week, placebo-controlled, double-blind, randomised study
      investigated the effects of sibutramine 20 mg once daily or placebo on body
      weight in 220 obese (body mass index (BMI) 27-40 kg/m2), hypertensive patients.
      At randomisation, hypertension was well controlled (< or = 95 mm Hg diastolic
      blood pressure (DBP)) with an angiotensin-converting enzyme (ACE) inhibitor, with
      or without concomitant thiazide diuretic therapy. Therapy for hypertension
      continued for the 52 weeks of the study. Sibutramine 20 mg produced significantly
      greater weight loss compared with placebo: 4.5 kg with sibutramine compared with
      0.4 kg with placebo (last observation carried forward (LOCF); P < or = 0.05). A
      total of 62 patients (42.8%) treated with sibutramine lost < or = 5% of their
      body weight compared with six patients (8.3%) treated with placebo; 19 patients
      (13.1%) treated with sibutramine lost > or = 10% of their body weight compared
      with two patients (2.8%) treated with placebo (LOCF; P < or = 0.05 for both
      comparisons). Hypertension remained well controlled for the 52 weeks of the study
      with both sibutramine and placebo treatment. After 52 weeks, the differences
      between placebo treatment and sibutramine treatment for both mean supine systolic
      blood pressure (SBP) and DBP were approximately 3 mm Hg: mean DBP was 82.8 mm Hg
      with placebo treatment compared with 85.5 mm Hg with sibutramine treatment (LOCF;
      P = 0.004) and mean SBP was 130.4 mm Hg with placebo compared with 133.1 mm Hg
      with sibutramine (LOCF; P = 0.0497; both comparisons, sibutramine vs placebo).
      The mean increases in SBP and DBP did not appear to change the overall risk
      category for coronary heart disease end points. Changes in pulse rate at week 52
      were a decrease of 0.3 beats per minute (bpm) for placebo treatment compared with
      an increase of 5.7 bpm for sibutramine treatment (P < 0.001). Mandated
      withdrawals from the study due to protocol-defined changes in BP were not
      statistically different between the two treatment groups. Greater favourable
      changes in lipid profile, serum glucose, and uric acid could be accounted for by
      greater weight losses occurring in the sibutramine treatment group. Sibutramine
      was well tolerated. This study indicates that in obese patients whose
      hypertension is well controlled at the outset with an ACE inhibitor, with or
      without concomitant thiazide diuretic therapy, sibutramine safely and effectively
      achieves weight loss without compromising good BP control.

PMID- 11840225
TI  - Efficacy and safety of sibutramine for weight loss in obese patients with
      hypertension well controlled by beta-adrenergic blocking agents: a placebo
      controlled, double-blind, randomised trial.
AB  - Sibutramine is a serotonin-noradrenaline reuptake inhibitor that is effective for
      long-term weight reduction and maintenance in obese patients when used as an
      adjunct to dietary and behavioural measures. Because the inhibition of
      noradrenaline reuptake may be expected to increase systolic and diastolic blood
      pressure (SBP and DBP) and pulse rate (PR), a 12-week multi-centre, placebo
      controlled, double-blind study was designed to evaluate the efficacy and
      tolerability of sibutramine for weight loss in obese patients whose hypertension
      was well controlled (DBP < or = 95 mm Hg) by beta-adrenergic blocking agents
      (beta-blockers), with or without concomitant thiazide diuretics. Of the 61
      patients randomised to sibutramine 20 mg once daily or placebo, 55 patients (90%)
      completed the study. After 12 weeks, sibutramine-treated patients lost
      significantly more weight than placebo-treated patients: mean weight reductions
      were 4.2 kg (4.5%) in the sibutramine group vs 0.3 kg (0.4%) in the placebo group
      (P<0.001). Greater weight reduction on sibutramine was accompanied by trends for
      greater mean reductions in serum triglycerides and very low density lipoprotein
      cholesterol. Sibutramine was well tolerated, and most adverse events were mild or
      moderate in severity. No sibutramine patient discontinued treatment because of an
      adverse event. Mean supine and standing DBP and SBP were not statistically
      significantly different between the sibutramine group and the placebo group at
      any post-baseline visit during the 12-week trial. At week 12, mean increases from
      baseline supine SBP and DBP, respectively, were 1.6 and 1.7 mm Hg for the
      sibutramine group vs increases of 0.4 and 1.3 mm Hg for the placebo group. At
      week 12, mean increases from baseline standing SBP and DBP, respectively, were
      1.5 and 1.8 mm Hg for the sibutramine group vs an increase of 0.3 and a decrease
      of 0.8 mm Hg for the placebo group (P > 0.05 for treatment comparison). A
      statistically significant mean increase of 5.6 bpm (+/-8.25, s.d.) in supine PR
      from a baseline of 62 bpm was reported in sibutramine-treated patients at week
      12, whereas placebo-treated patients had a mean supine PR decrease of 2.2 bpm (+/
      6.43) (P < 0.001). In summary, sibutramine was well tolerated and effective in
      weight reduction. The addition of sibutramine did not result in an increase in BP
      in obese patients whose hypertension was well controlled by a beta-blocker.
      However, based on the potential for changes in BP and PR, obese patients being
      treated with sibutramine should be monitored periodically for changes in BP and
      PR and managed appropriately.

PMID- 11840226
TI  - Weak effect of hypertension and other classic risk factors in the elderly who
      have already paid their toll.
AB  - The aim of the CASTEL, a population-based (n=3282) prospective study which began
      14 years ago, was to identify those items which had a prognostic impact in the
      elderly, and to evaluate whether the typical cardiovascular risk factors,
      particularly arterial hypertension, play a role after the age of 65 years.
      Initial screening, final follow-up and annual detection of mortality were
      performed. Mantel-Hanszel approach and multivariate Cox model were used for
      statistics. Cardiovascular mortality was 23.3% in normotensive, 23.3% in
      borderline, and 25% in the sustained hypertensive subjects (insignificant
      difference). In women, the incidence of stroke and coronary artery disease weakly
      depended on pulse pressure. Historical stroke and myocardial infarction predicted
      cardiovascular mortality in women; diabetes, uricaemia and high heart rate in
      men. In the very old, the predictors were less numerous, and blood pressure was
      not a predictor whatsoever; pulse blood pressure and murmurs at the neck were
      especially predictive in women, historical heart failure, proteinuria and
      tachycardia in men, historical stroke and myocardial infarction, pulmonary
      disease, left ventricular hypertrophy, diabetes and uricaemia in both genders.
      The elderly have a different cardiovascular risk pattern compared to younger
      people. Hypertension is not a predictor of coronary and stroke mortality.
      Prognosis depends on pulse pressure rather than on the label 'hypertension'.
      Hypercholesterolaemia is not a risk factor. This could simply indicate that
      elderly persons are the survivors in a population where significant mortality has
      already made its mark, eliminating those with the worst risk pattern. The two
      genders have a different risk profile due to sex-specific susceptibility to risk
      factors.

PMID- 11840227
TI  - Post exercise hypotension is not mediated by the serotonergic system in
      borderline hypertensive individuals.
AB  - Recent evidence from our laboratory and others have suggested that the mechanism
      for a decrease in resting blood pressure after an acute bout of exercise is a
      centrally mediated decrease in total peripheral resistance. This study examined
      the effect of the central serotonergic system on post exercise hypotension (PEH)
      in 11 borderline hypertensive individuals (nine male, two female) aged 24.5 +/-
      5.1 years. Each subject completed two, 30-min cycling bouts at 70% of VO2peak
      while under placebo or a selective serotonin re-uptake inhibitor (SSRI)
      treatment. Blood pressure was recorded directly from the radial artery, and
      treatments were randomised, double blinded and separated by at least 14 days.
      Baseline blood pressure was 145/72 mm Hg for systolic (SBP) and diastolic (DBP)
      respectively. Peripheral measures of serotonin (5-HT) were lower under SSRI
      treatment, whereas the major 5-HT metabolite, 5-hydroxyindoleacetic acid, was not
      significantly changed, indicating elevated central 5-HT levels. There was no
      difference in any of the haemodynamic variables between trials. Despite an
      increased heart rate for the initial 75 min post exercise, SBP was decreased as
      much as 23 mm Hg during the initial 60 min post exercise, after which it had
      returned to normal. DBP was unchanged after exercise. Circulating adrenaline
      (0.60 +/- 0.14 ng/mL to 1.3 +/- 1.6 ng/ml) and noradrenaline (0.27 +/- 0.31 ng/ml
      to 4.5 +/- 2.1 ng/ml) were significantly elevated during exercise. Both returned
      to pre-exercise levels within 15 min post exercise. Unexpectedly, oxygen uptake
      was slightly (5%), but significantly increased over the entire duration of the
      SSRI trial. We conclude that the central serotonergic system is not responsible
      for PEH in our borderline hypertensive population.

PMID- 11840228
TI  - Serum leptin levels in patients with primary hyperaldosteronism before and after
      treatment: relationships to insulin sensitivity.
AB  - BACKGROUND: Leptin is a protein hormone produced predominantly by adipocytes that
      plays a role in food intake regulation and a series of other physiological
      processes including blood pressure regulation. OBJECTIVES: The aim of our study
      was to compare serum leptin levels in patients with primary hyperaldosteronism
      (PA) with those of healthy subjects and to explore the relationship of serum
      leptin levels and the parameters of insulin action in these patients before and
      after surgical or pharmacological treatment. METHODS: Serum potassium, leptin,
      aldosterone, insulin levels and plasma renin activity were measured and
      hyperinsulinaemic euglycaemic clamp was performed in 11 patients with PA and 11
      healthy age-, gender- and body mass index (BMI)-matched subjects. In eight of 11
      patients the same measurements were repeated at least 6 months after surgical or
      pharmacological treatment. RESULTS: The basal serum leptin levels in PA patients
      did not significantly differ from those of healthy subjects (mean+/-s.e.m. 8.4+/
      1.9 vs 11.2+/-1.8 ng/ml, P=0.30), although their insulin sensitivity was
      significantly impaired (PA patients vs control subjects: glucose disposal rate in
      the last 20 min of clamp (M) 18.7+/-1.8 vs 30.6+/-3.3 micromol/kg/min, metabolic
      clearance rate of glucose (MCR(g)) 3.9+/-0.5 vs 7.2+/-1.1 ml/kg/min, P<0.05). The
      surgical or pharmacological treatment of PA patients increased significantly
      their serum leptin levels (10.9+/-3.7 vs 8.4+/-1.9 ng/ml, P<0.05) and
      simultaneously improved their insulin sensitivity. Basal serum leptin levels in
      both groups correlated positively with BMI and serum insulin levels. The inverse
      relationship between serum leptin levels and the insulin sensitivity parameters
      was found in both PA patients before treatment and healthy subjects. These
      relationships disappeared after treatment of PA patients except for those between
      serum leptin levels and MCR(g). CONCLUSION: Basal serum leptin levels in
      untreated patients with PA do not significantly differ from those of healthy
      subjects, but increase significantly after surgical or pharmacological treatment.
      The increase in serum leptin levels is paradoxically accompanied by the
      improvement of insulin sensitivity in these patients.

PMID- 11840229
TI  - Prevalence of hypertension in the adult population of Belgium: report of a
      worksite study, Attention Hypertension.
AB  - Hypertension remains a major cause of cardiovascular morbidity in Belgium.
      Information on the prevalence of hypertension in the working population is
      desirable. A worksite study of hypertension prevalence was carried out in Belgium
      where 3472 individuals were screened for 1 week. The result was that high blood
      pressure (> or = 140/90 mm Hg) was identified in approximately one-third of the
      men and one-quarter of the women even though the majority of subjects had no
      recorded history of hypertension. Associations were identified between age and
      systolic blood pressure and, in men, between systolic blood pressure and alcohol
      consumption. Most participants in the survey were unaware of their serum
      cholesterol level. The results of this survey suggest that a large proportion of
      subjects with high blood pressure in the Belgian working population remain
      unidentified and indicate a lack of awareness about other cardiovascular risk
      factors.

PMID- 11840230
TI  - Enhanced vasodilator responses to calcitonin gene-related peptide (CGRP) in
      subcutaneous arteries in human hypertension.
AB  - Isolated segments (1-2 mm) of small subcutaneous arteries (diameter 0.1-0.9 mm)
      and veins (0.1-1.0 mm) from patients with hypertension (essential n = 13,
      renovascular n = 6) and controls (n = 17) were examined. The relaxant responses
      to the sensory transmitters calcitonin gene-related peptide (CGRP) and substance
      P, and the contractile responses to potassium and noradrenaline were studied.
      Enhanced dilatory responses (E(max)) but no change in sensitivity (pEC50) were
      demonstrated in the arteries but not in the veins to CGRP in hypertensives (P <
      0.01) as compared with normotensives, and in the hypertensive subgroups
      (essential hypertension, P < 0.05; renovascular hypertension, P< 0.05). The
      relaxant responses to substance P were not altered either in arteries or in veins
      of hypertensives. Furthermore, there were no differences in the contractile
      responses to 60 mM potassium or to 10 microM noradrenaline between the groups.
      The results suggest that the enhanced vasodilator response to CGRP in
      hypertension is an adaptive reaction. The elevated blood pressure may be
      augmented by vasodilatory activity since different subgroups of hypertensives
      showed the same results. However, other common characteristics of hypertension
      (eg, medication, metabolic disturbances) may have also influenced the results.

PMID- 11840231
TI  - Relationship between left ventricular mass and blood pressure in treated
      hypertension.
AB  - This study evaluated prospectively whether there is still a relationship between
      left ventricular mass and blood pressure once hypertension is treated and
      determined the relative importance of daytime vs night-time blood pressure,
      systolic vs diastolic blood pressure and office vs ambulatory blood pressure. A
      total of 649 patients (305 or 47% female) with essential hypertension, treated
      with antihypertensive drugs for at least 3 months, underwent office blood
      pressure measurement and both daytime and night-time ambulatory blood pressure
      measurement, electrocardiography and echocardiography. Correlations were made
      between blood pressure values and parameters of left ventricular mass.
      Electrocardiographic voltage criteria and even more so echocardiographic
      parameters correlate significantly albeit weakly (r < or = 0.28) with blood
      pressure in treated hypertension. Correlations are consistently higher when
      systolic blood pressure is considered. Overall, the best correlations are found
      between 24-h ambulatory systolic or night-time blood pressure and the Sokolow
      Lyon voltage as well as the echocardiographic age and body mass index adjusted
      left ventricular mass. In conclusion, once hypertension is treated, the
      relationship between blood pressure and left ventricular mass is low.
      Nevertheless, in this the largest single centre study of its kind,
      echocardiographic parameters of left ventricular mass in treated hypertensive
      subjects correlate better with blood pressure than electrocardiographic
      parameters. Parameters of hypertrophy are more closely related to systolic blood
      pressure than to diastolic blood pressure. In accordance with the finding that
      dippers have a better prognosis than non-dippers, night-time blood pressure
      consistently correlates better with left ventricular mass than daytime blood
      pressure.

PMID- 11840232
TI  - Do siblings of myocardial infarction patients have a specific management of
      hypertension?
AB  - The aim of this study was to determine whether the management of hypertension
      differs between siblings of myocardial infarction patients and the general
      population. Siblings aged 35 to 74 years, unaffected by myocardial infarction,
      were drawn from the Augsburg Family Heart Study, conducted in 1996-1997 in
      southern Germany (n = 524). The reference group consisted of participants of the
      third MONICA population-based survey conducted in 1994-1995 in the same area, who
      were aged 35 to 74 years and also unaffected by myocardial infarction (n = 3802).
      Prevalence, awareness, treatment and control of hypertension (defined by blood
      pressure > or = 140/90 mm Hg or use of antihypertensive medication) were compared
      between the two groups. The result was that the prevalence of hypertension was
      higher in the siblings (men: age-adjusted OR = 1.31, 95% CI: 0.99-1.75; women:
      age-adjusted OR = 1.83, 95% CI: 1.39-2.41). Male hypertensive siblings were more
      often aware and treated for hypertension than male hypertensives of the reference
      group whereas the level of awareness and treatment was comparable between female
      hypertensives of the two groups. In both genders, no difference in the degree of
      control was shown between hypertensives of the two groups. In conclusion the
      siblings and their physicians should pay more attention to the family history of
      myocardial infarction in order to improve the management of hypertension in this
      high risk group.

PMID- 11840233
TI  - The role of the NICU in developing countries.

PMID- 11840234
TI  - Very-low-birth-weight infant outcomes in 11 South American NICUs.
AB  - OBJECTIVE: To describe and analyze outcomes in very-low-birth-weight (VLBW)
      infants treated in 11 Neonatal Intensive Care Units (NICUs) from four South
      American countries. This study is the first of a multination collaboration and
      can serve as a baseline for future quality and resource utilization efforts.
      STUDY DESIGN: Biodemographic data and multiple outcome measures were
      prospectively collected from October 1997 until August 1998. A logistic
      regression model was used to define risk factors in primary outcome measures,
      death, and bronchopulmonary dysplasia (BPD). Center differences were compared
      using chi-squared analysis. RESULTS: In 385 VLBW infants enrolled, mortality rate
      was 27%, with a range from 11% to 51% among NICUs. A lower BW, lower gestational
      age (GA), lack of antenatal steroids (AS), and air leaks (AL) were associated
      with increased risk of death. A lower BW, lower GA, AL, need for surfactant,
      necrotizing enterocolitis, and need for intubation were associated with increased
      risk of BPD. CONCLUSION: This study provides actual information about VLBW
      infants' prognosis in a SA region. Mortality rate variability among NICUs may be
      explained by differences in population and resources, but also by lack of
      implementation of proven beneficial therapies such as AS administration.

PMID- 11840235
TI  - Apnea at discharge and gastro-esophageal reflux in the preterm infant.
AB  - OBJECTIVE: To determine the relationship between respiratory patterns and acid
      gastro-esophageal reflux (g-e reflux) prior to discharge of the formerly preterm
      infant. STUDY DESIGN: Forty-five infants of <32 weeks' gestation were studied at
      an average postmenstrual age of 37.2 weeks (SD 3.5). Following informed parental
      consent, a 12-hour multichannel recording including esophageal pH was obtained.
      Apneas of greater than 10 seconds were recorded, as well as the occurrence of
      bradycardia or desaturation. RESULTS: Acid g-e reflux (pH <4.0) occurred at least
      once in all of the infants; prevalence was between <1% and 41% of the 12-hour
      record (median 4.6%, interquartile range 0.5% to 9%). The number of reflux
      episodes ranged from 1 to 143 (median 23). The number of apneas (>10 seconds
      duration) ranged from 0 to 71, median 6. There was no correlation between apnea
      frequency or severity and reflux frequency or duration. There was no difference
      in apnea frequencies between the 5 minutes after the start of a reflux episode
      and the 5 minutes prior to each episode. CONCLUSION: Acid g-e reflux in the
      formerly preterm infant at discharge is frequent and may be prolonged; there is
      no association between reflux and apnea.

PMID- 11840236
TI  - Improved transcutaneous bilirubinometry: comparison of SpectR(X) BiliCheck and
      Minolta Jaundice Meter JM-102 for estimating total serum bilirubin in a normal
      newborn population.
AB  - OBJECTIVE: To compare a new transcutaneous bilirubinometer, which uses multiple
      wavelength analysis of reflectance data (BiliCheck system), and the commonly used
      two-wavelength bilirubinometer (Jaundice Meter JM-102) to estimate serum
      bilirubin. STUDY DESIGN: Jaundiced newborn term infants (101 babies) had
      transcutaneous bilirubinometry (TCB) using each bilirubinometer, a determination
      of skin color using a skin color chart, and a total serum bilirubin
      determination. RESULTS: The variability of the BiliCheck system was less than the
      variability of the Jaundice Meter JM-102. The accuracy of the BiliCheck system
      was not affected by skin color, whereas the Jaundice Meter JM-102 was affected.
      CONCLUSION: Multiple wavelength analysis, as used in the BiliCheck system, is a
      significant improvement in TCB.

PMID- 11840237
TI  - Hidden morbidity with "successful" early discharge.
AB  - OBJECTIVE: This study was conducted to determine if early postnatal discharge
      (EDC; < or =48 hours) in well newborns had an effect on the rate of hospital
      readmission within the first week after hospital discharge when compared to
      infants who remained >48 hours after birth (later discharge, LDC). STUDY DESIGN:
      This was a retrospective medical chart review. Charts of infants born between
      January 1994 and December 1998, discharged as "well newborns" and treated
      subsequently at a primary children's hospital within 7 days of neonatal
      discharge, were reviewed. Infants were categorized by length of neonatal hospital
      stay, level of medical intervention (emergency department treatment or hospital
      admission), and final diagnosis. RESULTS: There was a significant increase in
      hospital readmission rate for LDC infants when compared to EDC infants. When
      considering jaundice alone as an admitting diagnosis, EDC infants were admitted
      at a higher rate than LDC infants and with higher serum bilirubin concentrations.
      Readmitted, jaundiced infants had been almost always breast-fed. CONCLUSION:
      Overall, EDC of well newborns appears to be a safe and reasonable practice.
      However, the risk for severe jaundice is an unresolved issue that requires a
      discharge strategy and early follow-up to prevent serious morbidity.

PMID- 11840238
TI  - The pattern of change in the lecithin/sphingomyelin ratio in patients with
      preterm premature rupture of membranes between 24 and 34 weeks' gestation.
AB  - OBJECTIVE: To report the pattern of change in the lecithin/sphingomyelin (L/S)
      ratio in patients with preterm premature rupture of membranes (PPROM) between 24
      and 34 weeks' gestation. STUDY DESIGN: L/S was determined prospectively using
      transvaginally and transabdominally collected amniotic fluid from patients with
      PPROM between 24 and 34 weeks' gestation. Samples were collected prospectively on
      admission and every 48 to 96 hours until L/S was > or =2.0. All patients received
      intramuscular betamethasone weekly. RESULTS: Fifty-five patients were included in
      the study. One hundred twenty-seven samples were collected transvaginally and
      nine were collected transabdominally. Cox regression analysis showed that a
      higher initial L/S value and more advanced gestational age were associated with
      accelerated lung maturation. Among patients at > or =29 weeks' gestation with an
      initial L/S of > or =1.5 and <2.0 (n=17), 15 of 17 (88%) reached L/S > or = 2 at
      a mean of 3.1 +/- 1.7 days (range 1.0 to 7.0 days). With an initial L/S of > or
      =1.0 and <1.5 (n=16), 14 of 16 (88%) patients reached L/S > or =2 at a mean of
      4.1 +/- 1.9 days (range 1.7 to 7.0 days). With an initial L/S of <1.0 (n=11), 6
      of 11 (54%) patients reached L/S > or =2 at a mean of 5.0 +/- 1.6 days (range 4.7
      to 6.8 days). CONCLUSION: Our data document a dramatic acceleration of fetal lung
      maturation among patients with PPROM at > or = 29 weeks.

PMID- 11840239
TI  - Snap-II predicts severe intraventricular hemorrhage and chronic lung disease in
      the neonatal intensive care unit.
AB  - OBJECTIVE: To determine whether the Score for Neonatal Acute Physiology, Version
      II (SNAP-II), improved prediction of severe (> or = grade III) intraventricular
      hemorrhage (IVH) and chronic lung disease (CLD) when compared to models using
      gestational age (GA) and traditional risk factors (e.g., Apgar score, small-for
      gestational-age, sex, outborn status). STUDY DESIGN: We examined 4226 infants <
      or = 32 weeks' GA admitted to 17 Canadian neonatal intensive care units between
      1996 and 1997. We compared prediction models for severe IVH and CLD, with and
      without SNAP-II. RESULTS: SNAP-II was a significant and independent predictor of
      severe IVH and CLD. Addition of SNAP-II to models using GA and traditional risk
      variables significantly (p<0.05) improved model prediction (AUC 0.8 for severe
      IVH; 0.83 for CLD). Models were well calibrated (p>0.05 for Hosmer-Lemeshow
      goodness of fit test). CONCLUSION: Addition of SNAP-II to models using GA and
      traditional risk factors significantly improves prediction of severe IVH and CLD.

PMID- 11840240
TI  - Patterns of physical and neurologic development in preterm children.
AB  - OBJECTIVE: To evaluate the influence of medical complications, gestational age,
      gender, ethnicity, and socioeconomic status on the changes in anthropometric
      measures and severity of neurologic impairment from 6 to 54 months of age in
      premature and term infants. STUDY DESIGN: This study was a prospective
      longitudinal study to determine predictors of patterns of growth and neurologic
      outcome in low-risk (n=137) and high-risk (n=96) preterm infants compared to full
      term infants (n=136). Growth modeling analyses were used to evaluate factors that
      might influence patterns of physical growth and changes in neurologic status.
      RESULTS: Medical risk level was a predictor of height and head circumference at
      30 months and neurologic outcome. Gender was a predictor of weight gain. Medical
      risk level and gender predicted 13.8% and 32% of the variance in head
      circumference and neurologic scores, respectively. CONCLUSION: Medical
      complications after birth and gender are stronger influences than gestational age
      on patterns of growth and neurologic outcome.

PMID- 11840241
TI  - Risk of cranial ultrasound abnormalities in very-low-birth-weight infants
      conceived with assisted reproductive techniques.
AB  - OBJECTIVE: To evaluate risks of cranial ultrasound abnormalities among very-low
      birth-weight (VLBW) infants conceived with fertility therapy (ovulation induction
      only or with assisted reproductive techniques [ART]) and of multiple gestation
      pregnancies. STUDY DESIGN: The incidences of cranial ultrasound abnormalities in
      1473 VLBW infants conceived with and without fertility therapy and born of
      multiple versus singleton pregnancies were compared, using logistic regression
      models. RESULTS: Infants conceived with ART were less likely to have
      intraventricular hemorrhage (IVH). Twins and triplets had risks of cranial
      ultrasound abnormalities similar to those of singletons. Twins and triplets
      conceived with ART were at lower risk of IVH. CONCLUSION: VLBW infants conceived
      with ART do not appear to be at increased risk of cranial ultrasound
      abnormalities. Likewise, twins and triplets were not at increased risk of these
      abnormalities.

PMID- 11840242
TI  - Continuous oxygen monitoring of the conjunctiva in neonates.
AB  - OBJECTIVE: To report the first use of a noninvasive conjunctival oxygen monitor
      in neonates. We wished to investigate if measuring the partial pressure of oxygen
      directly from the conjunctiva could track hyperoxia and hypoxia as well as, or
      better than, pulse oximetry. This has the potential to reflect brain oxygenation
      while yielding important systemic information. STUDY DESIGN: Criteria standard.
      SETTING: Tertiary care hospital neonatal intensive care unit. PATIENTS: Ten
      newborns monitored with pulse oximetry. INTERVENTION: The conjunctival oxygen
      monitor was studied for effectiveness and safety and compared to pulse oximetry.
      RESULTS: The device remained on the eyes up to 120 minutes. The correlation
      coefficient between conjunctival oxygen tension and pulse oximetry was
      significant for all readings (p<0.001) and for pulse oximetry measurements below
      100% (p=0.024). One infant developed eyelid edema, which subsided when the device
      was removed and one sustained a small corneal abrasion that healed overnight.
      CONCLUSION: This initial pilot report suggests that the conjunctival oxygen
      monitor is effective and relatively safe in neonates. The device holds promise to
      indicate a tissue oxygen reading, which may provide neonatologists with more
      information about systemic oxygenation.

PMID- 11840243
TI  - Feasibility of nitric oxide administration by oxygen hood in neonatal pulmonary
      hypertension.
AB  - OBJECTIVE: To test the hemodynamic efficacy and feasibility of nitric oxide (NO)
      administration by oxygen hood in neonatal pulmonary hypertension. STUDY DESIGN: A
      double-hood apparatus was used in which a combination of NO, O(2), and N(2) was
      introduced into the inner hood and suctioned from the outer hood. Chronically
      instrumented non-intubated piglets were exposed to 10% O(2) (hypoxia; n=8) or
      group B streptococci infusion (GBS; n=5) to produce pulmonary hypertension and
      were then exposed to 20 ppm NO. RESULTS: NO decreased (>50%) pulmonary artery
      pressure and vascular resistance in both hypoxia- and GBS-induced pulmonary
      hypertension, with minimal effects on systemic arterial pressure and cardiac
      output. NO administration could be performed without detectable environmental
      leakage. CONCLUSION: Hood NO administration is feasible and shows hemodynamic
      efficacy in neonatal piglets with pulmonary hypertension.

PMID- 11840244
TI  - Parents' perceptions of research with newborns.
AB  - OBJECTIVE: To examine beliefs and attitudes of parents about research with
      babies. STUDY DESIGN: Survey of 72 parents of newborn babies in the neonatal
      intensive care unit (NICU), and 159 parents of normal newborns using instrument
      designed for the study. The instrument included questions with graded responses
      and five research scenarios with varied risks and benefits. Statistical analysis
      included chi(2) analysis and Fisher's exact test. RESULTS: Parents showed
      generally favorable attitudes toward research with babies. There were few
      differences between the two groups of parents, but there was a trend toward more
      trust in doctors by "NICU parents." Couples with newborns in NICU were
      significantly more likely to enroll their newborn in a study involving moderate
      risk and possible major direct benefit. Almost a third of the sample in both
      groups was willing to enroll their newborn in a study with moderate risk and no
      direct benefit. CONCLUSION: Parents believe research is necessary and want to be
      asked for consent, but many feel they have limited knowledge and would depend on
      their physician's advice. The fact, that some might enroll their newborn in a
      study involving a risky procedure that would not benefit the newborn, supports
      the notion of vulnerability and emphasizes the fact that physicians must be alert
      to the possibility of coercion and undue influence.

PMID- 11840245
TI  - Indices of hemodynamic and respiratory functions in premature infants at risk for
      the development of cerebral white matter injury.
AB  - OBJECTIVE: To examine potential differences in clinical risk factors, including
      indices of hemodynamic and respiratory functions, of premature infants developing
      periventricular hemorrhagic infarction (PHI) or periventricular leukomalacia
      (PVL). STUDY DESIGN: Indices of hemodynamic stability and respiratory function
      were measured prospectively during the first week of life in a cohort of 100
      premature infants with respiratory distress. Maternal history was retrospectively
      reviewed. These data were correlated with cranial ultrasonography using one-way
      ANOVA, Bonferroni multiple comparisons, and Wilcoxon rank sum tests. Longitudinal
      analysis was performed using Generalized Estimating Equations. RESULTS: Fifty-two
      infants with normal cranial ultrasound studies were compared to 12 with PHI and 9
      with PVL. Infants developing PHI had significantly lower birth weights, lower
      Apgar scores, were more often male and multiple gestations, and required more
      vasopressor support than infants with normal ultrasound studies. Infants with PHI
      had significantly worse indices of respiratory function than either normal
      infants or those with PVL. PVL was significantly associated with maternal
      chorioamnionitis, whereas PHI was not. CONCLUSION: These data suggest that there
      are important differences in the pathogenesis of PHI and PVL. A clear
      understanding of these differences is required before future preventive
      strategies can be formulated.

PMID- 11840246
TI  - Misguided good intentions.
AB  - A 3-day-old infant unexpectedly developed cardiopulmonary arrest at home. A
      resuscitation process was initiated and the infant was transported to a nearby
      community hospital where a highly respected senior pediatrician assumed
      responsibility for the prolonged resuscitation. Following cessation of aggressive
      support measures, the infant resumed gasping/respiratory efforts. The
      pediatrician admitted to occluding the infant's nose and mouth just before death.
      Several of the important medical issues and ethical distinctions are discussed.

PMID- 11840247
TI  - The role of the French midwives in establishing the first special care units for
      sick newborns.
AB  - At the end of the 19th century, under Dr. Tarnier's direction, the first trials
      of incubators were performed at the Paris Maternity. The success led to the
      construction of a special pavilion for sick newborns. The midwife-in-chief, Mrs.
      Henry, raised the funds for the construction. The results of the initial trial
      are reported. In 1892, the successor of Dr. Tarnier, Dr. Budin, the Chair of
      Obstetrics, did not approve of the condition of the nursery. Mrs. Henry left
      abruptly. The unit was placed under medical direction in order to bring a
      scientific approach to the care of the sick newborns. Stepdown units called
      pouponnieres were created to assure the transition of the infants to the home and
      decrease neonatal mortality.

PMID- 11840248
TI  - Breast-feeding promotion interventions: good public health and economic sense.
AB  - The health benefits of breast-feeding are well documented, as are the positive
      effects of breast-feeding promotion interventions. There is a clear dose-response
      relationship between breast-feeding and infant health in the first year of life,
      and beyond. Further, nearly all breast-feeding promotion interventions improve-
      at least minimally--breast-feeding initiation and duration rates. However, the
      extent to which the costs of such interventions might be offset by the potential
      health care cost savings during the infant's first year of life has not been
      examined. From a health policy perspective, such an economic analysis is
      indicated.

PMID- 11840249
TI  - Inhaled nitric oxide for oligohydramnios-induced pulmonary hypoplasia: a report
      of two cases and review of the literature.
AB  - We describe the clinical courses of two premature infants, a male born at 29(4/7)
      weeks' gestational age after an 8-week period of rupture of membranes (ROM) and
      severe oligohydramnios, and a female infant born at 31 weeks' gestational age
      after an 18-week period of ROM and severe oligohydramnios. Within hours after
      birth, despite intubation and aggressive ventilation, both infants developed
      fulminant hypoxic respiratory failure. Their clinical courses were consistent
      with pulmonary hypertension and both infants were transferred for trials of
      inhaled nitric oxide (iNO). Both infants had dramatic responses to iNO,
      suggesting that the pulmonary disease seen after prolonged oligohydramnios may
      have a component of nitric oxide-sensitive pulmonary hypertension. The goals of
      this article are to (1) review oligohydramnios-induced pulmonary hypoplasia, (2)
      discuss patients at highest mortality risk, and (3) describe the effects of iNO
      on pulmonary hypertension in infants with hypoxemia following prolonged ROM and
      severe oligohydramnios.

PMID- 11840250
TI  - Fetal demise due to herpes simplex virus: an illustrated case report.
AB  - We report and illustrate a case of fetal demise at 31 weeks caused by fulminant
      herpes simplex virus (HSV) infection. The 15-year-old mother reported no past
      history or symptoms of an HSV infection during pregnancy. Autopsy revealed
      extensively ulcerated skin and necrosis of the liver, adrenal glands, brain, and
      placental membranes. Fluorescent in situ hybridization studies of the lungs,
      liver, adrenal glands and placenta were positive for HSV, but did not distinguish
      between HSV-1 and HSV-2. A maternal postpartum blood sample was positive for HSV
      2 by immunoblot assay.

PMID- 11840251
TI  - Transposition of the great arteries and hypocalcemia in a patient with fetal
      hydantoin syndrome.
AB  - We report a patient with fetal hydantoin syndrome (FHS) with associated d
      transposition of the great arteries (d-TGA) and persistent hypocalcemia. d-TGA
      and hypocalcemia have each been individually reported once in association with
      FHS, but these patients were also prenatally exposed to phenobarbital. To our
      knowledge, this is the first report of these problems occurring after prenatal
      exposure to hydantoin alone. The combination of congenital heart disease and
      hypocalcemia in our patient raises the possibility of a hydantoin effect on
      neural crest migration.

PMID- 11840252
TI  - Newborn with transverse facial cleft associated with polyhydramnios.
AB  - We describe here the case of a female newborn baby with a bilateral complete
      transverse facial cleft. Obstetrical ultrasound had revealed an increased amount
      of amniotic fluid from 28 weeks' gestation without fetal hydrops or congenital
      anomalies. A 1900-g baby girl born at 36 weeks' gestation presented with
      bilateral wide facial clefts with macrostomia, microphthalmia, nose, and
      auricular deformities. Her breathing was dependent on life support, which was
      discontinued 2 hours after birth. An autopsy revealed no congenital malformations
      in vital organs but the absence of the olfactory nerves. Polyhydramnios and
      respiratory arrest after birth were presumed to be due to central disintegration
      of swallowing and breathing, in this case with brain anomaly.

PMID- 11840253
TI  - Aicardi syndrome with probable intraorbital cystic encephalocele.

PMID- 11840256
TI  - Thalidomide for the treatment of patients with myelodysplastic syndromes.
AB  - We examined the efficacy of thalidomide in 34 patients with myelodysplastic
      syndromes (MDS): five RAEB-T, four RAEB, three CMML, six RARS, and 16 RA.
      Patients belonged to the following cytogenetic groups: 15 complex abnormal
      karyotypes, 12 normal karyotypes, four cases with 5q- as sole anomaly and three
      single aberrations. The median thalidomide dose was 400 mg/day (25/34 patients).
      Four patients discontinued the study after less than 5 weeks, because of fatigue
      (three) or skin rash (one). One patient died of heart failure after 4 weeks. In
      the remaining 29 patients (median follow-up: 13 months), treatment responses were
      classified according to the IWG criteria. Six patients (four RA, two CMML) showed
      progressive disease (five with transformation into AML) and four patients showed
      stable disease. Hematological improvement (HI) was observed in 19 patients. Nine
      of the responders (three RA, one RARS, two RAEB, three RAEB-T) achieved partial
      remission with granulocytes > or = 1500/microl, Hb > 11 g/dl and platelets > or
      =100,000/microl. Four patients (one RARS, one CMML, one RAEB, one RAEB-T) had a
      major response, with platelet and RBC transfusion independence. Six patients
      (five RA, one RARS) showed minor responses (three HI-E, two HI-E+HI-P, one HI
      E+HI-N). Hematological improvement occurred after a median of 2 months of
      thalidomide treatment. Two patients (RAEB-T) relapsed after a partial remission
      lasting 8 and 16 months, respectively. In summary, a therapeutic benefit was
      achieved in 19 of 34 study patients (56%).

PMID- 11840257
TI  - Translocation t(5;14)(q35;q32) in three cases of childhood T cell acute
      lymphoblastic leukemia: a new recurring and cryptic abnormality.
AB  - We report three cases of T-ALL in which conventional cytogenetic analysis yielded
      normal karyotypes, but for which a new M-FISH technique (IPM-FISH) was able to
      detect a translocation. For these patients this technique highlighted a new,
      recurring and cryptic translocation t(5;14)(q35;q32) in childhood T-ALL which
      might be phenotypically restricted. The most innovative part of this technique is
      the use of interspersed polymerase chain reaction (IRS-PCR) painting probes that
      show an R-band pattern simultaneous with the combinatorial labeling. Contrary to
      the DOP-PCR, IRS-PCR-derived probes provide stronger hybridization signals at the
      telomeric ends that potentially increase the possibility of detecting cryptic
      translocations. All the IPM-FISH findings were validated by FISH with whole
      chromosome painting and unique sequence probes. These results demonstrate the
      efficient use of IPM-FISH as an improved, single-step method for the
      identification of cryptic chromosomal abnormalities. This new IPM-FISH technique
      is a good tool to display cryptic chromosomal abnormalities.

PMID- 11840258
TI  - Long-term follow-up of persisting mixed chimerism after partially T cell-depleted
      allogeneic stem cell transplantation.
AB  - Using red cell phenotyping (RCP) and/or cytogenetics (CYT) we identified 19
      patients with persisting mixed chimerism (MC) among 231 patients transplanted
      with partially T cell-depleted stem cell grafts from HLA-identical siblings.
      Persisting MC is defined as MC for more than 2 years in patients without any
      evidence of relapse. Median leukemia-free survival in these patients was 150
      (range, 50-218) months. Diagnoses were ALL (n= 10); AML (n = 2); CML (n = 2); NHL
      (n = 2); MDS (n= 1); MM (n = 1) and SAA (n = 1). Purpose of this study was the
      long-term follow-up of MC and definition of patterns of chimerism in the various
      subsets of PBMCs and granulocytes. Using a PCR-STR technique CD3(+)/CD4(+) (T4
      lymphocytes), CD3(+)/CD8(+) (T8 lymphocytes), CD45(+)/CD19(+) (B lymphocytes),
      CD45(+)/CD14(+) (monocytes), CD45(+)/CD15(+) (granulocytes) and CD3(-)/CD56(+)
      (NK-cells) were analyzed. The majority of patients with persisting MC were
      conditioned with a less intensive conditioning regimen and had little GVHD.
      Sequential monitoring of the chimerism resulted in a group of patients (n = 7)
      with very slow transient mixed chimerism that resulted in complete DC after
      median 7 years. Another nine patients had a relatively high percentage of
      persisting autologous cells for a median of 12 years and in three patients we
      observed a stable low percentage of autologous cells. Only two out of 19 patients
      (AML-CR1, CML-CP1) relapsed during follow-up. Both patients had a relatively high
      percentage of autologous cells. Chimerism in granulocytes and PBMC subsets was
      analyzed at a median of 8 years after SCT in nine patients. In five patients
      mixed chimerism simultaneously detected by RCP and CYT was associated with MC in
      all subsets. Within each individual patient the percentages of donor and
      recipient cells were very different between the different subsets. Two CML-CP1
      patients were mixed chimera in only two subsets and in one patient these subsets
      represented pending relapse. In another two patients mixed chimerism with a very
      low number of autologous red cells was not found in the PBMCs because of the
      different sensitivity level of the RCP and the PCR-STR technique. We conclude
      that in patients with persisting mixed chimerism after partially T cell-depleted
      SCT a remarkable number of patients had lymphoid malignancies, the majority of
      the patients were conditioned with less intensive conditioning regimens and the
      mixed chimerism was not correlated with relapse. Chimerism in granulocytes and
      PBMC subsets did show great intra-individual differences in the subsets and these
      data correlated well with RCP and CYT data with the exception of the NK cells.

PMID- 11840259
TI  - High Bad and Bax mRNA expression correlate with negative outcome in acute myeloid
      leukemia (AML).
AB  - The search for molecular markers in AML that allow prediction of outcome has
      recently focused on genes involved in the regulation of programmed cell death
      (PCD). The aim of our study was to determine whether mRNA levels of Mdm-2, Bcl-2,
      Bcl-x(L), Bad, and Bax are independent prognostic parameters for outcome.
      Transcript levels were analyzed by real-time quantitative RT-PCR in 232 samples
      collected either at diagnosis or following induction chemotherapy (ICT).
      Multivariate COX regression analysis adjusted for chemotherapy protocol, de novo
      vs secondary AML, and de novo vs relapsed AML indicated: (1) At diagnosis, high
      expression of Bad (P = 0.015) and even more so high Bax and Bad levels (P =
      0.018) predicted adverse outcome, regardless of the response to ICT. In patients
      who subsequently failed to enter complete remission (CR), high levels of Bad, Bax
      and Bax high/Bad high were associated with an increased relative risk (RR) to die
      from tumor (RR = 5.0 for Bad, 3.4 for Bax and 6.14 for Bax high/Bad high). (2)
      Following ICT, high expression of Bax (P= 0.005) and high Bcl-2/Bax ratios (P =
      0.004) were independent predictors of unfavorable outcome, regardless of response
      to ICT. We conclude that high levels of Bax and Bad correlate with poor outcome,
      particularly in patients who do not enter CR and may serve as prognostic markers
      in AML.

PMID- 11840260
TI  - CD38 expression is an important prognostic marker in chronic lymphocytic
      leukaemia.
AB  - Employing a multicolour flow cytometry assay, 133 B-chronic lymphocytic leukaemia
      (B-CLL) cases were analysed for surface expression of CD38. Based on a cut-off
      value of 20%, CLL patients were categorised into a CD38-positive (> or = 20%, n =
      56) and a CD38-negative subgroup (< 20%, n = 77) and separately analysed for
      clinical and laboratory parameters. Patients in the CD38-positive cohort were
      characterised by an unfavourable clinical course with a more advanced disease
      stage, poor responsiveness to chemotherapy, short time to initiation of first
      treatment and shorter survival. In contrast, the CD38- negative group required
      minimal or no treatment, remained treatment-free for a longer time period and had
      prolonged survival (P < 0.05). CD38 expression was a robust marker in the
      majority of patients in that it was stable over time and not significantly
      influenced by chemotherapy. In conclusion, our data confirm recent studies
      suggesting a role of CD38 as a predictor of clinical outcome in patients with B
      CLL.

PMID- 11840261
TI  - 2-Chloro-2'-deoxyadenosine inhibits DNA repair synthesis and potentiates UVC
      cytotoxicity in chronic lymphocytic leukemia B lymphocytes.
AB  - 2-Chloro-2'-deoxyadenosine (CdA) is a deoxyadenosine analogue which targets
      enzymes involved in DNA synthesis, and hence might interfere with the resynthesis
      step of DNA repair. We tested this hypothesis in resting B cell chronic
      lymphocytic leukemia (B-CLL) lymphocytes, after firstly characterizing
      unscheduled DNA synthesis occurring in these cells. We observed that the
      spontaneous incorporation of [methyl-3H]thymidine (dThd) into DNA of B-CLL cells
      was not completely inhibitable by hydroxyurea (HU) which blocks DNA replication.
      In addition, in the presence of HU, dThd incorporation could be upregulated by
      UVC radiation or DNA alkylation, without re-entry of the cells into S phase. CdA
      was found to inhibit both spontaneous and upregulated DNA synthesis in B-CLL
      cells. Phosphorylation of CdA was essential to exert this effect. We finally
      observed a strong synergistic cytotoxicity between UV light and CdA, which was
      correlated with activation of caspase-3 and high molecular weight DNA
      fragmentation, two markers of apoptosis. Taken together, these observations
      indicate that in B-CLL cells CdA inhibits unscheduled DNA synthesis which
      represents the polymerizing step of a repair process responsive to DNA
      aggression. Inhibition of this process by CdA, together with a combined
      activation of the apoptotic proteolytic cascade by CdA and UV, may explain their
      synergistic cytotoxicity.

PMID- 11840262
TI  - CD5-induced apoptosis of B cells in some patients with chronic lymphocytic
      leukemia.
AB  - Although B chronic lymphocytic leukemia (B-CLL) is characterized by prolonged
      survival of CD5(+) B cells in vivo, these cells apoptose spontaneously in vitro.
      The effect of CD5 ligation on apoptosis was studied in 27 newly diagnosed
      patients with B-CLL, in relation to the expression of surface IgM (sIgM), CD79b,
      CD38, CD72 and CD19. B cells from 15 patients (group I) were resistant to anti
      CD5-induced apoptosis, whereas apoptosis above spontaneous levels was seen in the
      remaining 12 studied (group II). Group II was then subdivided on the basis of
      differences in the time required to reach maximum apoptosis: whilst B cells from
      seven patients underwent apoptosis by 18 h, those from the remaining five needed
      36 h to apoptose. The expression of sIgM, CD5, CD79b and CD38 was higher in group
      II than group I, suggesting that signaling for apoptosis might operate via CD79,
      and that CD38 expression was required. As shown by flow cytometry and confirmed
      by Western blotting, apoptosis was associated with a decrease in the ratios of
      Bcl-2/Bax and Bcl(XL)/Bax, due to an increase in the level of Bax, but no change
      in that of Bcl-2. This heterogeneous apoptotic response to CD5 ligation offers an
      explanation for the incomplete success of anti-CD5 monoclonal therapy, and might
      help identify patients who would respond to such treatment.

PMID- 11840263
TI  - Comparison of chromosome banding analysis, interphase- and hypermetaphase-FISH,
      qualitative and quantitative PCR for diagnosis and for follow-up in chronic
      myeloid leukemia: a study on 350 cases.
AB  - For the diagnosis of CML and for monitoring of treatment response the detection
      of the t(9;22)(q34;q11) or the BCR-ABL rearrangement is necessary. Chromosome
      banding analysis (CA) is still the gold standard but other techniques like
      Southern blot, fluorescence in situ hybridization (FISH) and polymerase chain
      reaction (PCR) are available. We analyzed 350 CML patients at different stages of
      disease in parallel with CA, interphase-FISH (IP-FISH), hypermetaphase-FISH (HM
      FISH) and RT-PCR. In 20 cases with no Ph(+) metaphases in CA, HM-FISH detected
      0.2 to 10% BCR-ABL(+)metaphases. After IP-FISH 107 samples were judged as
      negative. However, in 17 of these samples HM-FISH detected BCR-ABL(+) metaphases
      (0.3-11%), and in eight cases CA detected Ph(+) metaphases (2.5-25%). A
      comparison of IP-FISH performed on uncultivated cells vs cells cultivated for 48
      h in 70 cases revealed a higher proportion of BCR-ABL+ cells in the cultivated
      samples. If nested PCR was negative, all other methods were negative in all cases
      too. In addition, 94 cases were evaluated using real-time PCR (LightCycler
      technology). The BCR-ABL/cABL ratio measured showed a high correlation with all
      other methods. Interestingly, a wide range in the BCR-ABL/ABL ratio was observed
      especially in patients who showed 100% Ph-positive metaphases in CA. In
      conclusion, CA, IP-FISH, HM-FISH and real-time PCR give reliable results but
      differences due to measurement of different target structures have to be kept in
      mind when using these data for definition of remission status.

PMID- 11840264
TI  - Radioimmunotherapy for model B cell malignancies using 90Y-labeled anti-CD19 and
      anti-CD20 monoclonal antibodies.
AB  - In recent years, radioimmunotherapy (RIT) with beta(-) particle emitting
      radionuclides targeting the CD20 antigen on B cells in the treatment of non
      Hodgkin's lymphoma has provided the most compelling human clinical data for the
      success of RIT. CD19, like CD20, is an antigen expressed on the surface of cells
      of the B lineage, and CD19 may provide an alternative target for
      radioimmunotherapy of B cell neoplasms. CD19 has been largely overlooked as a
      target for conventional 131I RIT, because the antigen rapidly internalizes upon
      binding of antibody, resulting in catabolism and significant release of 131I.
      Such modulation may be an advantage to RIT with radiometals such as 90Y, 177Lu,
      213Bi and 225Ac. Herein, we have compared beta(-) particle RIT with antibodies
      targeting either CD19 or CD20. The anti-CD19 and anti-CD20 antibodies, B4 or
      C2B8, respectively, were appended with the SCN-CHX-A''-DTPA bifunctional
      chelating agent and labeled with 90Y. In the tumor model used, there were three
      times as many CD20 target sites on lymphoma cells as compared to CD19 sites
      (62000 vs 20000 binding sites, respectively). We compared the efficacy of the 90Y
      labeled antibodies to reduce lymphoma in a nude mouse xenograft solid tumor
      model, after measurable lymphoma appeared. Reduction in tumor size began at day 3
      in all three 90Y-treated groups, but tumor began to recur in many animals 9 days
      after the treatments. There was one cure in each specific treatment group. In
      contrast, the tumor in the two control groups showed no regression. There was a
      significant prolongation of median survival time from xenograft (P < 0.0001) in
      all the 90Y-labeled antibody construct-treated groups (32 days for 0.15 mCi 90Y
      B4; 26 days for 0.20 mCi 90Y-C2B8, and 23 days for 0.15 mCi 90Y-C2B8) in
      comparison to the two control groups (11 days for 0.02 mg of C2B8 and 9 days for
      untreated growth controls). Specificity of the radioimmunotherapy was also shown.
      In conclusion, 90Y-labeled anti-CD19 antibody has efficacy comparable to 90Y
      labeled anti-CD20 antibody in the treatment of mice bearing human lymphoma
      xenografts. These data suggest that CD19-targeted RIT merits further study.

PMID- 11840266
TI  - Ajoene, an experimental anti-leukemic drug: mechanism of cell death.
AB  - The organosulfur compound ajoene, a constitutent of garlic, has been shown to
      induce apoptosis in a leukemic cell line as well as in blood cells of a leukemic
      patient. The mechanisms of action of ajoene, however, are unknown. The present
      study aims to characterize the molecular events leading to ajoene-triggered
      apoptosis. We show here that ajoene (20 microM) leads to a time-dependent
      activation of caspase-3-like activity as well as to the proteolytic processing of
      procaspase-3 and -8. Activation of caspases was necessary for ajoene-induced
      apoptosis since the broad-range caspase inhibitor zVAD-fmk completely abrogated
      ajoene-mediated DNA fragmentation. Although the initiator caspase-8 was
      activated, the CD95 death receptor was not involved in death signaling since the
      HL-60 clone used was shown to express a functionally inactive CD95 receptor.
      Furthermore, ajoene induced the release of cytochrome c, which was not inhibited
      by zVAD-fmk indicating that cytochrome c release precedes caspase activation.
      Ajoene also led to a dissipation of the mitochondrial transmembrane potential.
      Overexpression of Bcl-x(L) clearly diminished ajoene-induced caspase activation
      as well as apoptosis. These results indicate that apoptosis in leukemia cells
      triggered by ajoene is based on the activation of a mitochondria-dependent
      caspase cascade which includes also the activation of the initiator caspase-8.

PMID- 11840265
TI  - TRAIL (Apo2L) suppresses growth of primary human leukemia and myelodysplasia
      progenitors.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL, APO2L) has been
      shown to induce apoptosis in a number of tumor cell lines as well as in some
      primary tumors whereas cells from most normal tissues are highly resistant to
      TRAIL-induced apoptosis. We have studied the susceptibility of primary malignant
      and normal bone marrow hematopoietic progenitors to TRAIL-induced apoptosis.
      Extracellular domain of human TRAIL with N-terminal His(6) tag (His-TRAIL, amino
      acids 95-281) was produced in E. coli and its apoptosis-inducing ability was
      compared with the leucine-zipper containing TRAIL, LZ-TRAIL. Both variants of
      TRAIL had the same apoptosis-inducing ability. Clonogenic progenitor assays
      showed that His-TRAIL significantly reduced the number of myeloid colonies (CFU
      GM) and clusters from patients with acute myeloid leukemia (AML), chronic myeloid
      leukemia (CML), and myelodysplastic syndromes (MDS). His-TRAIL had no negative
      effect on the number of CFU-GM colonies and clusters derived from bone marrow
      cells of AML patients in complete remission, and lymphoma patients without bone
      marrow involvement, as well as those derived from normal cord blood cells.
      Moreover, we found that normal human stem cells treated with high doses of His
      TRAIL maintain a repopulating potential when transplanted into NOD/SCID mice. To
      conclude, our data document that TRAIL does not affect normal human hematopoiesis
      but suppresses the growth of early primary leukemia and myelodysplasia
      progenitors.

PMID- 11840267
TI  - Primary acute myeloid leukaemia blasts resistant to cytokine-induced
      differentiation to dendritic-like leukaemia cells can be forced to differentiate
      by the addition of bryostatin-1.
AB  - Primary acute myeloid leukaemia (AML) blasts can be induced to differentiate into
      dendritic-like leukaemia cells (DLLC) by culture with certain cytokine
      combinations. DLLC offer potential for use as autologous vaccines based on their
      ability to present putative leukaemia-specific antigens to T cells. It has been
      reported, however, that in around 30-50% of AML cases the leukaemia cells are not
      capable of undergoing DLLC differentiation. The purpose of this study was to
      identify the features that represent successful DLLC differentiation and, for
      those cases shown to be resistant to cytokine-induced differentiation, to use
      differentiating agents in an attempt to overcome the differentiation block.
      Leukaemia cells derived from 42 patients with AML were cultured in vitro with
      cytokines GM-CSF, IL-4 and TNFalpha/CD40L. In 22 cases the leukaemic cells
      underwent DLLC differentiation based on characteristic morphological changes and
      expression of costimulatory and dendritic cell-associated molecules. Four cases
      were not evaluable because of poor viability over the culture period. The
      remaining 16 cases failed to show evidence of DLLC differentiation. Many of these
      differentiation resistant cases were associated with poor risk karyotypic
      features. Nine of the resistant cases were selected for further study.
      Differentiating agents trichostatin (TSA), azacytidine (AZA) and bryostatin
      (BRYO) were used in combination with cytokines for the first 96 h of the culture
      period. Bryostatin (BRYO) alone was shown to be capable of overcoming
      differentiation resistance and allowing DLLC differentiation to proceed.

PMID- 11840269
TI  - Retroviral transfer and expression of human MDR-1 in a murine haemopoietic stem
      cell line does not alter factor dependence, growth or differentiation
      characteristics.
AB  - In view of the recent report of a myeloproliferative syndrome in mice that had
      received an MDR-1-transduced haemopoietic graft, we have investigated the
      potential effects of MDR-1 expression on primitive haemopoietic cell growth and
      differentiation. Retroviral gene transfer was used to achieve exogenous
      expression of either MDR-1 or truncated nerve growth factor receptor (tNGFR) in
      the multipotent murine haemopoietic progenitor cell line, FDCP-mix. Following
      gene transfer, clonal lines were derived and FACS analysis confirmed appropriate
      expression of each transgene. MDR-1 (but not tNGFR) expression was associated
      with verapamil-sensitive rhodamine efflux and resistance to killing by etoposide.
      When growth factor responsiveness, proliferative capacity and differentiation
      capacity were examined, MDR-1 expressing FDCP-mix cells exhibited a normal
      phenotype and mimicked the response of tNGFR-expressing or untransduced FDCP-mix
      cells. Thus, in the model system we have used, MDR-1 does not perturb
      haemopoietic cell growth and development and our data do not support a
      myeloproliferative role for MDR-1.

PMID- 11840268
TI  - Transforming growth factor-beta1 transcriptionally activates CD34 and prevents
      induced differentiation of TF-1 cells in the absence of any cell-cycle effects.
AB  - A number of cytokines modulate self-renewal and differentiation of hematopoietic
      elements. Among these is transforming growth factor beta1 (TGF-beta1), which
      regulates cell cycle and differentiation of hematopoietic cells, but has
      pleiotropic activities depending on the state of responsiveness of the target
      cells. It has been previously shown by us and other authors that TGF-beta1
      maintains human CD34(+) hematopoietic progenitors in an undifferentiated state,
      independently of any cell cycle effects, and that depletion of TGF-beta1 triggers
      differentiation accompanied by a decrease in CD34 antigen expression. In the
      present work, we show that exogenous TGF-beta1 upregulates the human CD34 antigen
      in the CD34(+) cell lines TF-1 and KG-1a, but not in the more differentiated
      CD34(-) cell lines HL-60 and K-562. We further studied this effect in the
      pluripotent erythroleukemia cell line TF-1. Here, TGF-beta1 did not effect cell
      growth, but induced transcriptional activation of full-length CD34 and prevented
      differentiation induced by differentiating agents. This effect was associated
      with nuclear translocation of Smad-2, activation of TAK-1, and with a dramatic
      decrease in p38 phosphorylation. In other systems TGF-beta1 has been shown to
      activate a TGF-beta-activated kinase 1 (TAK1), which in turn, activates p38. The
      specific inhibitor of p38 phosphorylation, SB202190, also increased CD34 RNA
      expression, indicating the existence of a link between p-38 inhibition by TGF
      beta1 and CD34 overexpression. Our data demonstrate that TGF-beta1
      transcriptionally activates CD34 and prevents differentiation of TF-1 cells by
      acting independently through the Smad, TAK1 and p38 pathways, and thus provide
      important clues for the understanding of hematopoietic development and a
      potential tool to modify response of hematopoietic cells to mitogens or
      differentiating agents.

PMID- 11840271
TI  - Alternative end-joining in follicular lymphomas' t(14;18) translocation.
AB  - T(14;18) chromosomal translocation is assumed to result from illegitimate
      rearrangement between the BCL2 proto-oncogene and the IGH locus during the D(H)
      to J(H) joining phase of V(D)J recombination in early B cells. Analysis of the
      breakpoint junctions suggests that translocation derives from the fusion between
      normal V(D)J recombination intermediates at the IGH locus and non-V(D)J-mediated
      broken-ends at the BCL2 locus. So far, BCL2 broken-ends have only been observed
      fused to coding-ends, raising questions concerning the molecular constraints of
      the illegitimate joining process. Using a combination of genome walking and long
      range PCR assays, we describe in this report that in 4.5% (2/44) of the t(14;18),
      one of the BCL2 broken-ends is fused to a signal-end. The formation of these
      J(H)RSS/BCL2 junctions provides direct evidence that BCL2 broken-ends are capable
      of joining to both products of V(D)J recombination, suggesting their presence in
      the RAG-mediated post-cleavage complex. In addition, junctions generated by this
      alternative end-joining do not involve deletion of the chromosome 14 intervening
      sequences generally lost in the standard translocation, providing a unique
      opportunity to investigate the rearrangement status of this region in the
      translocated IGH allele. In both cases, a DJ(H) rearrangement could be detected
      5' of the J(H)-RSS/BCL2 junction. These findings, together with the previously
      reported bias towards the most external D(H) and J(H) segments in standard
      breakpoints, strongly suggest that t(14;18) preferentially occurs during an
      attempted secondary D(H) to J(H) rearrangement. This unusual and restricted
      window of differentiation opens intriguing questions concerning the etiology of
      the translocation.

PMID- 11840270
TI  - Expression of endothelial cell-associated molecules in AML cells.
AB  - Recently, it has been clarified that interaction between hematopoietic cells and
      endothelial cells is important in normal hematopoiesis and leukemogenesis. In
      this study, we examined the relationship between AML cells and endothelial cells
      by analyzing the expression profile of angiogenic factors, angiopoietin-1 (Ang
      1), Ang-2, Tie-2 (a receptor for angiopoietins) and vascular endothelial growth
      factor (VEGF). Our results demonstrated that CD7(+)AML expressed Ang-2 mRNA
      frequently and integrin-family adhesion molecules (CD11c and CD18) intensively,
      suggesting the close correlation with endothelial cells. On the other hand, in
      t(8;21) AML cells, expression of Ang-2 was infrequent and expression of integrin
      family adhesion molecules (CD11b, CD11c and CD18) was weak, suggesting the sparse
      association with endothelial cells. As for CD7(+)AML cells, despite the frequent
      and intense expression of endothelial cell-associated molecules (such as Ang-2,
      CD11c and CD18), intensity of Tie-2 expression was quite low (P < 0.05). Ang-2
      expressed in CD7(+)AML cells is not considered to act in an autocrine fashion,
      but to work on endothelial cells to "feed" leukemic cells. Although Ang-2 is
      recognized as a natural antagonist for Tie-2, our data presented here suggested
      the alternative role of Ang-2 in the relationship between endothelial cells and
      leukemia cells, at least in a subset of leukemia such as CD7(+)AML. These results
      were supported by the study using AML cell lines, KG-1 (CD7 negative) and its
      subline KG-1a (CD7 positive); KG-1 had mRNA expression profile of Ang-1(+)Ang-2(
      )Tie-2(+), while KG-1a showed Ang-1(+)Ang-2(+)Tie-2(-). These difference in the
      expression profile of angiogenic factors between CD7(+)AML and t(8;21)AML may
      explain the characteristic morphological features of these leukemias (CD7(+)AML
      as blastic type and t(8;21)AML as differentiative type).

PMID- 11840272
TI  - Frequent inactivation of the cyclin-dependent kinase inhibitor p18 by homozygous
      deletion in multiple myeloma cell lines: ectopic p18 expression inhibits growth
      and induces apoptosis.
AB  - Multiple myeloma (MM) is a clonal neoplasm of plasma cells which offers an
      excellent model to study multistep molecular oncogenesis. In 20-25% of primary
      tumors and cell lines examined, cyclin D1 is overexpressed due to the
      translocation t(11;14)(q13;q32). We have characterized cyclin-dependent kinase
      inhibitor p15 (CDKN2B), p16 (CDKN2A) and p18 (CDKN2C) deletions in cyclin D1
      expressing and non-expressing MM cell lines. p18 was found to be frequently
      deleted (38%); in some cases p18 deletions coexisted with hemizygous p16
      deletion. To examine the function of p18 as a putative tumor suppressor in
      myeloma cells, a zinc-inducible p18 construct was stably transfected into KMS12,
      a MM cell line with biallelic p18 and monoallelic p16 deletions as well as cyclin
      D1 overexpression. Ectopic expression of p18 caused 40-45% growth suppression as
      determined by trypan blue exclusion and MTS assays. p18 induction also resulted
      in apoptosis, suggesting that inhibition of the cyclin D1/CDK/pRb pathway in
      these tumor cells could be a crucial step toward the induction of tumor
      regression via apoptotic cell death. This cell cycle pathway is thus frequently
      mutated and provides a potentially novel target for gene therapeutic or
      pharmacologic approaches to human myeloma.

PMID- 11840273
TI  - CD44 variant isoforms are involved in plasma cell adhesion to bone marrow stromal
      cells.
AB  - Expression of CD44v9-containing isoforms (CD44v9) on myeloma plasma cells
      correlates with unfavorable prognosis, suggesting that CD44 variant molecules are
      involved in the disease process. In this study, the presence of CD44v on B cell
      lines from different stages of development was analyzed by flow cytometry and a
      role in adhesion to stromal cells from different tissues was evaluated in in
      vitro binding assays. CD44v3, v6 and v9 isoforms were exclusively expressed on
      plasma cell lines and CD44v9 expression correlated with IL-6-dependent plasma
      cell growth. Binding studies using CD44 isoform- specific reagents showed that
      CD44v6 and CD44v9 were involved in binding to bone marrow stromal cells, but not
      to in vitro synthesized ECM or hyaluronic acid. CD44v9-mediated plasma cell
      binding resulted in a significant induction of IL-6 secretion by bone marrow
      stromal cells. Large differences in quantitative plasma cell binding to stromal
      cells from different tissues were observed. These, however, could not be related
      to a differential use of CD44v in these binding processes. The role of CD44v9 in
      adhesion induced IL-6 secretion and its preferential expression on IL-6-dependent
      plasma cell lines may explain the previously observed correlation between CD44v9
      expression and adverse prognosis in multiple myeloma.

PMID- 11840274
TI  - Rapid detection of leukemia-associated translocation fusion genes using a novel
      combined RT-PCR and flow cytometric method.
AB  - Efficient detection of recurrent translocation-associated fusion genes is of
      critical importance for the diagnosis, prognosis and post-therapeutic monitoring
      of many leukemias. Typically, the presence of such translocations is revealed by
      RT-PCR technique, followed by Southern blot hybridization to ensure specificity
      of the PCR product. Though widely employed, post-PCR analysis of this type is
      relatively laborious and time-intensive. As a departure from standard analytic
      approaches, we have developed a robust novel method combining both high
      specificity and sensitivity, based on polystyrene bead capture of fluorescently
      labeled PCR products, with subsequent analysis by flow cytometry. Results from
      cell line and patient sample evaluations indicate that this method may be easily
      incorporated into the diagnostic molecular laboratory as a rapid and cost
      effective alternative to currently employed techniques.

PMID- 11840275
TI  - Acute myeloblastic leukemia (AML) with inv (16)(p13;q22) and the rare I type
      CBFbeta-MYH11 transcript: report of two new cases.

PMID- 11840276
TI  - Co-existence of pseudo-Chediak-Higashi anomaly and double minutes containing C
      MYC oncogene in three patients with AML M2.

PMID- 11840277
TI  - High incidence of point mutations of p53 suppressor oncogene in patients with
      myelodysplastic syndrome among atomic-bomb survivors: a 10-year follow-up.

PMID- 11840279
TI  - Retinoic acid syndrome: a problem of the past?

PMID- 11840278
TI  - Hematopoietic cell transplantation beyond first remission.

PMID- 11840280
TI  - Soluble TNF receptor fusion protein (etanercept) for the treatment of
      myelodysplastic syndrome: a pilot study.
AB  - Blockade of tumor necrosis factor (TNF)alpha by a soluble TNF receptor fusion
      protein (etanercept; Enbrel) improved in vitro hemopoiesis from the marrow of
      patients with myelodysplastic syndrome (MDS). Therefore, we enrolled 14 MDS
      patients (4 RA, 2 RARS, 6 RAEB, 2 CMML), 44-80 (median 60) years old, in a pilot
      trial. Etanercept, 25 mg, was given twice a week s.c. for 16 weeks (increased to
      three times a week if no response at 8 weeks). Among 12 evaluable patients, four
      had rises in hemoglobin by 1-1.5 gm/dl (three) or decreased transfusion
      requirements (one). Two patients had increased platelet counts (54% and 73%), and
      two increased neutrophils (63% and 120%). Baseline TNFalpha levels, determined in
      all patients, did not correlate with responses. Among eight marrows available for
      sequential in vitro assays, four showed increases in CFU-GM of 1.5- to 5-fold at
      8 weeks, whereas three showed 3- to 10-fold decrements relative to baseline.
      Thus, etanercept treatment resulted in moderate improvements of cytopenias in
      some patients, while cell counts declined in others. Additional trials are needed
      to evaluate its clinical efficacy in MDS.

PMID- 11840281
TI  - Elevated plasma level of differentiation inhibitory factor nm23-H1 protein
      correlates with risk factors for myelodysplastic syndrome.
AB  - We measured plasma nm23-H1 level (nm23-H1), a differentiation inhibitory factor,
      by an enzyme-linked immunosorbent assay (ELISA) in patients with aplastic anemia
      (AA) and myelodysplastic syndrome (MDS). The nm23-H1 in AA was not significantly
      elevated when compared to normal subjects (6.66 +/- 1.20 ng/ml vs 5.13 +/- 0.81
      ng/ml; P = 0.274). In contrast, MDS patients had significantly high levels of
      nm23-H1 compared not only to normal subjects (11.16 +/- 1.42 vs 5.13 +/- 0.81
      ng/ml; P = 0.0004) but also to those of the AA group (11.16 +/- 1.42 ng/ml vs
      6.66 +/- 1.20 ng/ml; P = 0.018). In the MDS group of patients, no significant
      difference was observed in the nm23-H1 levels between patients with refractory
      anemia (RA) and RA with excess blasts (RAEB)/RAEB in transformation (10.71 +/-
      1.61 ng/ml vs 9.24 +/- 2.66 ng/ml; P = 0.672). Of the patients with RA, patients
      with low risk according to the International Prognostic Scoring System (IPSS) had
      significantly low levels of nm23-H1 compared to those of IPSS INT-1 level cases
      (6.40 +/- 1.36 ng/ml vs 13.05 +/- 2.50 ng/ml; P = 0.0028), suggesting that nm23
      H1 may be useful as a prognostic marker for MDS, especially in low risk patients.

PMID- 11840282
TI  - Abnormality of c-kit oncoprotein in certain patients with chronic myelogenous
      leukemia--potential clinical significance.
AB  - Chronic myelogenous leukemia (CML) is characterized by the Philadelphia (Ph)
      chromosome and bcr/abl gene rearrangement which occurs in pluripotent
      hematopoietic progenitor cells expressing the c-kit receptor tyrosine kinase
      (KIT). To elucidate the biological properties of KIT in CML leukemogenesis, we
      performed analysis of alterations of the c-kit gene and functional analysis of
      altered KIT proteins. Gene alterations in the c-kit juxtamembrane domain of 80
      CML cases were analyzed by reverse transcriptase and polymerase chain reaction
      single strand conformation polymorphism (RT-PCR-SSCP). One case had an
      abnormality at codon 564 (AAT --> AAG, Asn --> Lys), and six cases had the same
      base abnormality at codon 541 (ATG --> CTG, Met --> Leu) in the juxtamembrane
      domain. Because the change from Met to Leu at codon 541 was a conservative one
      which was also observed in the normal population and normal tissues of CML
      patients, it probably represents a polymorphic variation. Although samples of
      hair roots and leukemic cells from the chronic phase of one CML patient showed no
      abnormality, an abnormality at codon 541 (ATG --> CTG, Met --> Leu) was found
      only at blastic crisis (BC) of this case. In the case with the abnormality at
      codon 564, the mutation was detected only in a sample of leukemic cells collected
      at BC. To examine the biological consequence and biological significance of these
      abnormalities, murine KIT(L540) and KIT(K563) expression vectors were introduced
      into interleukin-3 (IL-3)-dependent murine Ba/F3 cells to study their state of
      tyrosine phosphorylation and their growth rate. Ba/F3 cells expressing KIT(WT),
      KIT(L540) and KIT(K563) showed dose-dependent tyrosine phosphorylation after
      treatment with increasing concentrations of recombinant mouse stem cell factor
      (rmSCF). The cells expressing KIT(L540) and KIT(K563) were found to have greater
      tyrosine phosphorylation than cells expressing KIT(WT) at 0.1 and 1.0 ng/ml of
      rmSCF. The Ba/F3 cells expressing KIT(K563) proliferated in response to 0.1 and
      1.0 ng/ml of rmSCF as well as IL-3. The Ba/F3 cells expressing KIT(L540)showed a
      relatively higher proliferative response to 0.1 ng/ml of rmSCF than the response
      of cells expressing KIT(WT). These mutations and in vitro functional analyses
      raise the possibility that the KIT abnormalities influence the white blood cell
      counts (P < 0.05) and survival (P < 0.04) of CML patients.

PMID- 11840283
TI  - Surface antigen expression in chronic lymphocytic leukemia: clustering analysis,
      interrelationships and effects of chromosomal abnormalities.
AB  - Chronic lymphocytic leukemia (CLL) is a phenotypically distinguishable form of B
      lymphoid leukemias. The regularity of surface membrane antigen expression
      patterns, their interrelationships as well as the effects of the three frequent
      chromosomal aberrations, ie 11q deletion, 13q deletion and trisomy 12, were
      investigated in 35 classic CLL cases by flow cytometry. The two-way cluster
      analysis of 31 individual antigens revealed three expression patterns: (1) most
      cells in most cases positive (CD5, CD19, CD20, CD23, CD27, CD40, CD45, CD45RA);
      (2) most cells in most cases negative (CD10, CD14, CD34, CD122, CD154, mIgG); and
      (3) a mixed pattern with a variable number of positive cases and a variable
      percentage of positive cells in individual cases (CD11c, CD21, CD22, CD25, CD38,
      CD45RO, CD79b, CD80, CD95, CD124, CD126, CD130, FMC7, mIgD, mIgkappa, mIglambda,
      mIgM). The expressions of several antigens were strongly interdependent, even
      when antigens belonged to entirely different gene families. Such antigen pairs
      were: CD11c/CD21; CD19/CD45; CD19/CD79b; CD22/CD45RA; CD23/Igkappa; CD25/mIgM;
      CD27/CD45; CD45/CD79b; CD45RA/Igkappa. In contrast, the expression of some
      antigens was mutually exclusive, the best examples being CD45RA/CD45RO, CD38/CD80
      and CD45RA/CD80. Deletion of chromosome arm 11q attenuated expression of splicing
      variant CD45RA, but enhanced CD45RO expression. In contrast, cases of trisomy 12
      were associated with enhanced CD45RA and attenuated CD45RO expression. Similarly,
      trisomy 12 was associated with enhanced CD27 and mIgkappa expression. The
      variable levels of signaling surface membrane antigens, their interactions and
      interference by genetic aberrations are likely to affect the clinical progression
      and drug response of CLL.

PMID- 11840284
TI  - Quantitative HOX expression in chromosomally defined subsets of acute myelogenous
      leukemia.
AB  - We used a degenerate RT-PCR screen and subsequent real-time quantitative RT-PCR
      assays to examine the expression of HOX and TALE-family genes in 34 cases of
      chromosomally defined AML for which outcome data were available. AMLs with
      favorable cytogenetic features were associated with low overall HOX gene
      expression whereas poor prognostic cases had high levels. Characteristically,
      multiple HOXA family members including HOXA3-HOXA10 were jointly overexpressed in
      conjunction with HOXB3, HOXB6, MEIS1 and PBX3. Higher levels of expression were
      also observed in the FAB subtype, AML-M1. Spearmann correlation coefficients
      indicated that the expression levels for many of these genes were highly inter
      related. While we did not detect any significant correlations between HOX
      expression and complete response rates or age in this limited set of patients,
      there was a significant correlation between event-free survival and HOXA7 with a
      trend toward significance for HoxA9, HoxA4 and HoxA5. While patients with
      elevated HOX expression did worse, there were notable exceptions. Thus, although
      HOX overexpression and clinical resistance to chemotherapy often coincide, they
      are not inextricably linked. Our results indicate that quantitative HOX analysis
      has the potential to add new information to the management of patients with AML,
      especially where characteristic chromosomal alterations are lacking.

PMID- 11840285
TI  - Clinical and biological implications of partial tandem duplication of the MLL
      gene in acute myeloid leukemia without chromosomal abnormalities at 11q23.
AB  - The clinical and biological features of acute myeloid leukemia (AML) with
      11q23/MLL translocations are well known, but the characteristics of AML with
      partial tandem duplication of the MLL gene have not been explored
      comprehensively. In this study, MLL duplication was analyzed, in 81 AML patients
      without chromosomal abnormalities at 11q23, using Southern blotting, genomic DNA
      polymerase chain reaction (PCR), reverse-transcription PCR and complementary DNA
      sequencing. Nine patients showed partial tandem duplication of the MLL gene,
      including eight (12%) of the 68 with normal karyotype. Seven patients showed
      fusion of exon 6/exon 2 (e6/e2), one, combination of differentially spliced
      transcripts e7/e2 and e6/e2, and the remaining one, combination of e8/e2 and
      e7/e2. Among the patients with normal karyotype, children aged 1 to 15 showed a
      trend to higher frequency of MLL duplication than other patients (2/5 or 40% vs
      6/62 or 10%, P = 0.102). The patients with tandem duplication of the MLL gene had
      a significantly higher incidence of CD11b expression on leukemic cells than did
      those without in the subgroup of patients with normal karyotype (75% vs 28%, P =
      0.017). There were no significant differences in the expression of lymphoid
      antigens or other myeloid antigens between the two groups of patients. In adults,
      the patients with MLL duplication had a shorter median survival time than those
      without (4.5 months vs 12 months, P = 0.036). In conclusion, partial tandem
      duplication of the MLL gene is associated with increased expression of CD11b on
      leukemic blasts and implicates poor prognosis in adult AML patients. The higher
      frequency of MLL duplication in children older than 1 year, than in other age
      groups, needs to be confirmed by further studies.

PMID- 11840286
TI  - Prognostic significance of the null genotype of glutathione S-transferase-T1 in
      patients with acute myeloid leukemia: increased early death after chemotherapy.
AB  - We investigated the prognostic significance of genetic polymorphism in
      glutathione-S transferase mu 1 (GSTM1), glutathione-S transferase theta 1
      (GSTT1), NAD(P)H:quinone oxidoreductase (NQO1) and myeloperoxidase (MPO), the
      products of which are associated with drug metabolism as well as with
      detoxication, in 193 patients with de novo acute myeloid leukemia (AML) other
      than M3. Of the patients, 64.2% were either homozygous or heterozygous for GSTT1
      (GSTT1(+)), while 35.8% showed homozygous deletions of GSTT1 (GSTT1(-)). The
      GSTT1(-) group had a worse prognosis than the GSTT1(+) group (P = 0.04), whereas
      other genotypes did not affect the outcome. Multivariate analysis revealed that
      GSTT1(-) was an independent prognostic factor for overall survival (relative
      risk: 1.53; P = 0.026) but not for disease-free survival of 140 patients who
      achieved complete remission (CR). The rate of early death after the initiation of
      chemotherapy was higher in the GSTT1(-) group than the GSTT1(+) group (within 45
      days after initial chemotherapy, P = 0.073; within 120 days, P = 0.028), whereas
      CR rates and relapse frequencies were similar. The null genotype of GSTT1 might
      be associated with increased toxicity after chemotherapy.

PMID- 11840287
TI  - Effect of methotrexate polyglutamates on thioguanine nucleotide concentrations
      during continuation therapy of acute lymphoblastic leukemia with mercaptopurine.
AB  - Methotrexate is widely administered with mercaptopurine, a prodrug requiring
      activation into thioguanine nucleotides (TGN) to exert antileukemic effects. In
      vitro, methotrexate enhances TGN formation, but in vivo, such enhancement has yet
      to be demonstrated. We investigated whether TGN concentrations were related to
      methotrexate concentrations in children with acute lymphoblastic leukemia who
      received a weekly intravenous methotrexate (40 mg/m(2)) dose combined with daily
      mercaptopurine (75 mg/m(2)). A total of 141 erythrocyte TGN concentrations were
      measured with erythrocyte methotrexate polyglutamates (MTX-PG) concentrations in
      87 patients. Average TGN concentrations ranged from 137 to 958 pmol/8 x 10(8)
      cells (median 389), average total MTX-PG concentrations (MTX- PG(1-7)) from 0.60
      to 97.7 pmol/10(9)cells (median 29), and average long chain polyglutamate
      concentrations (MTX-PG(5-7)) from 0 to 8.35 pmol/10(9) cells (median 2.43).
      Higher TGN concentrations correlated with higher MTX-PG(5-7) concentrations (P =
      0.002). These data support the practice of administering methotrexate with
      mercaptopurine during continuation therapy of acute lymphoblastic leukemia.

PMID- 11840289
TI  - Diversity of the apoptotic response to chemotherapy in childhood leukemia.
AB  - Apoptosis is the primary mechanism through which most chemotherapeutic agents
      induce tumor cell death. The purpose of this study was to determine the extent to
      which blasts from children with leukemia undergo a uniform apoptotic death
      pathway in vivo. The expression of pro- and anti-apoptotic proteins p53, p21, MDM
      2, BCL-2, BCL-X(L), BCL-X(S), and BAX, and caspase-3 activity was determined in
      circulating blasts collected from the peripheral blood of children with leukemia
      prior to, and at serial time points following chemotherapy. Culturing blasts ex
      vivo for 12 h assessed spontaneous apoptosis and the increment induced by
      chemotherapy. Baseline apoptosis varied between 3% and 29%. Twenty-four hours
      following chemotherapy the increase in the percentage of cells undergoing
      apoptosis ranged from <1% to 38%. Eleven of 20 patients who received initial
      treatment with a p53-dependent drug showed an increase in p53 expression. In
      these patients, the levels of p53 target genes were also increased. A uniform
      pattern of BCL-2 family protein expression was not observed and only a minority
      of samples showed a change that would favor apoptosis. We conclude that that the
      initial apoptotic response to chemotherapy in children with leukemia is variable
      involving both p53-dependent and p53-independent pathways.

PMID- 11840290
TI  - C-Jun modulates apoptosis but not terminal cell differentiation in murine
      erythroleukemia cells.
AB  - The proto-oncogene c-Jun has been implicated in the control of cell proliferation
      and differentiation and more recently in the regulation of apoptosis. We have
      previously reported the involvement of c-Jun in the erythroid differentiation
      block in murine erythroleukemia (MEL) cells. As reported here, we investigated
      the role of c-Jun in the regulation of terminal differentiation and apoptosis of
      MEL cells by studying different stable transfectant clones containing c-jun
      constructs in sense or antisense orientation. c-Jun did not prevent cell growth
      arrest in G0/G1 and p21 induction that are normally associated with terminal
      differentiation induced by DMSO treatment, suggesting that c-Jun may uncouple
      phenotypic differentiation and terminal cell division in the MEL cell system.
      Spontaneous apoptosis was accelerated in c-jun expressing MEL cells before and
      after DMSO treatment. Moreover, c-Jun sensitized apoptosis induced by various
      drugs. Drug-induced apoptosis was associated with c-Jun N-terminal kinase (JNK)
      activation and c-Jun N-terminal phosphorylation (JNP). In contrast,
      overexpression of c-jun delayed apoptosis in serum-starved cells, indicating that
      c-Jun may reduce or accelerate apoptosis in MEL cells depending on the nature of
      the apoptotic stimulus. These results suggest that the proto-oncogene c-Jun may
      modulate differentiation and apoptosis of leukemic cells.

PMID- 11840288
TI  - Antileukemia activity of perillyl alcohol (POH): uncoupling apoptosis from G0/G1
      arrest suggests that the primary effect of POH on Bcr/Abl-transformed cells is to
      induce growth arrest.
AB  - In hematopoietic cells, the Bcr/Abl tyrosine kinase that is encoded by the
      Philadelphia chromosome translocation both stimulates proliferation and activates
      an anti-apoptotic program that is associated with a G2/M delay upon exposure to
      various apoptotic stimuli. We recently reported that the monocyclic monoterpene,
      perillyl alcohol (POH) selectively induces in Bcr/Abl transformed cells, G0/G1
      arrest and apoptosis. Therefore, POH activates anti-proliferative and apoptotic
      pathways against which the Bcr/Abl kinase does not protect. In this report, we
      show that in Bcr/Abl-transformed cells, POH induces cytoplasmic acidification,
      redistribution of phosphatidylserine in the plasma membrane along with DNA
      fragmentation, all of which can be prevented by the phorbol ester, TPA. The
      ability of TPA to protect against POH-induced cytotoxicity was blocked by
      inhibitors of protein kinase C (PKC) and the Na(+)/H(+) antiport. In contrast,
      TPA does not protect the cells from POH-mediated G0/G1 arrest. While POH inhibits
      a distal step in the mevalonate biosynthesis pathway, lovastatin, also a
      potential anticancer agent, inhibits the initial step in this pathway. Not
      surprisingly, lovastatin also induces G0/G1 arrest and apoptosis in Bcr/Abl
      transformed cells, however, TPA protects cells from both apoptosis and G0/G1
      arrest caused by lovastatin. Thus, in Bcr/Abl-transformed cells, POH and
      lovastatin cause growth arrest by different mechanisms. Together, these
      observations demonstrate that POH-mediated cell cycle arrest precedes apoptosis
      and raises the possibility that that the primary effect of POH is to induce G0/G1
      arrest with apoptosis being a consequence of the growth arrest.

PMID- 11840292
TI  - Expression of a human endogenous retrovirus, HERV-K, in the blood cells of
      leukemia patients.
AB  - Human endogenous retroviral sequences (HERVs) are believed to be possible
      pathogenic agents in carcinogenesis. HERV-K is the most biologically active form,
      since members of this family have intact open reading frames for the gag, pol or
      env genes. Antibody response against HERV-K peptides has been reported in
      leukemia patients, suggesting a possible overexpression of this sequence in
      leukemic cells. Using real-time quantitative RT-PCR (TaqMan), we found that in
      six of the eight leukemia samples we collected, transcriptional activity of HERV
      K10-like gag gene was 5- to 10-fold higher than in normal peripheral blood
      mononuclear cells (PBMCs) or mononuclear cells from cord blood. The
      overexpression was marked enough to be detected by Northern blot. In addition,
      there was no significant variation of HERV-K expression in normal PBMCs after
      exposure to different factors (PHA, gamma irradiation, 5-azacytidine) that
      potentially modulate HERV expression. This suggests that HERV-K relative
      overexpression in leukemia samples might be specifically associated with tumor
      development. The origin of these transcriptional variations is therefore worth
      being investigated further.

PMID- 11840291
TI  - Extracellular signal-regulated kinase and p38 mitogen-activated protein kinase
      pathways cooperate in mediating cytokine-induced proliferation of a leukemic cell
      line.
AB  - Granulocyte colony-stimulating factor (G-CSF) and fetal liver tyrosine kinase-3
      (Flt3) ligand (FL) act in synergy to induce expansion and mobilization of
      hematopoietic progenitor cells. Regulation of mitogen activated protein (MAP)
      kinase pathways and gene transcription, induced by these cytokines were examined
      using the OCI-AML5 cell line. For this purpose, FL and G-CSF were used either
      alone, or in combination as the co-addition of FL and G-CSF (FL+G-CSF), or a
      chimeric molecule, progenipoietin-1 (ProGP-1). Both G-CSF and FL induced
      phosphorylation of extracellular signal-regulated kinases (ERKs) while p38
      mitogen activated protein (MAP) kinase was phosphorylated only in response to G
      CSF but not FL. Studies using specific kinase inhibitors suggested that both ERK
      and p38 MAP kinase pathways were required for the optimal cell proliferation in
      response to both G-CSF and FL. The magnitude of activation of the ERK pathway and
      induction of genes involved in cell cycle progression by G-CSF and FL exhibited a
      strong correlation with the degree of cell proliferation. These data suggest that
      OCI-AML5 cells proliferate at least in part, due to the activation of both ERK
      and p38 MAP kinase pathways in response to G-CSF and FL. This study represents
      the first report of the specific cell cycle genes induced by FL.

PMID- 11840293
TI  - Positron emission tomography with [18F]2-fluoro-D-2-deoxyglucose (FDG-PET)
      predicts relapse of malignant lymphoma after high-dose therapy with stem cell
      transplantation.
AB  - We have determined the predictive value of [18F]2-fluoro-2-deoxy-glucose (FDG
      PET) in patients with Hodgkin's disease (HD) and aggressive non-Hodgkin's
      lymphoma (NHL) scheduled for high-dose therapy with stem cell transplantation
      (HDT/SCT). Inclusion criteria were the presence of an FDG-PET scan after
      chemotherapy (ChT) within 8 weeks prior to HDT/SCT and available follow-up data.
      Sixteen patients (10 NHL and six HD) were observed during a follow-up period of 4
      to 28 months (median 13 months). Before SCT, five patients had a negative PET,
      three were weakly positive, two moderately positive, and six strongly positive.
      None of the five patients with a negative PET before HDT/SCT relapsed and two of
      three patients with a weakly positive scan are still in remission after HDT/SCT.
      Of eight patients with a moderate or high positive PET before HDT/SCT, seven
      relapsed and one died of early HDT/SCT related complications (P< 0.01). Three of
      eight relapsing patients died of lymphoma 5 to 10 months after SCT and in one
      additional patient not responding to HDT/SCT, the main cause of death was chronic
      toxicity 4 months after transplantation. After 12 months, in PET-negative
      patients the overall and relapse-free survival was 100%, in PET-positive patients
      55% and 18%, respectively. In NHL, two patients with negative PET, but with an
      age-adjusted international prognostic index (AaIPI) of 2 and one with AaIPI = 1
      are still in remission. In the seven PET-positive subjects, one patient with
      AaIPI = 0, three with AaIPI = 1, and two with AaIPI = 2 relapsed. We conclude
      that FDG-PET is accurate in the prediction of relapse prior to HDT/SCT in
      patients with lymphoma. It provides additional information when compared with the
      AaIPI.

PMID- 11840294
TI  - Point mutations of the BCL-6 gene: clinical and prognostic correlation in B
      diffuse large cell lymphoma.
AB  - Although point mutations of the 5' noncoding regions of the BCL-6 proto-oncogene
      are frequently detected in B-diffuse large cell lymphoma (B-DLCL), a thorough
      analysis of the clinical correlation of these mutations has not been performed to
      date. In this study, BCL-6 mutations were examined by DNA direct sequencing in
      103 patients with B-DLCL. BCL-6 mutations were found in 53/103 patients,
      including 38/76 treated with standard chemotherapy and 15/27 treated with
      autologous stem cell transplantation (ASCT) up front. The presence of BCL-6
      mutations was correlated with clinical features at diagnosis and outcome. Mutated
      patients had a significantly higher LDH level (66% vs 38%, P < 0.05), and bulky
      disease (51% vs 32%, P = 0.05). In the whole series of patients BCL-6 mutations
      did not affect CR and OS. Patients with BCL-6 mutations tended to have a
      prolonged 5-years DFS and FFS compared to those without mutations (DFS 82% vs
      63%, FFS 63% vs 49%). Among B-DLCL treated with standard chemotherapy, mutated
      patients showed a significantly improved 5-year DFS (85% vs 61%, P < 0.05) and,
      notably, the only four relapses observed among mutated patients occurred in less
      than 8 months. The multivariate regression analysis (P < 0.01) with DFS as
      endpoint confirmed the independent prognostic value of BCL-6 mutations. There was
      a trend for 5-year failure-free survival to be better for patients with BCL-6
      mutations (63% vs 43%, P = 0.09). In the 27 patients treated with ASCT, BCL-6
      mutations did not correlate with outcome. These results suggest that BCL-6
      mutations may predict a higher chance of being free of disease in B-DLCL treated
      with standard chemotherapy. Larger series of patients need to be analyzed to
      evaluate the clinical relevance of BCL-6 mutations properly.

PMID- 11840295
TI  - Establishment and comprehensive analysis of a new human transformed follicular
      lymphoma B cell line, Tat-1.
AB  - A spontaneously EBV transformed follicular lymphoma (FL) cell line, Tat-1, was
      established from the lymph node biopsy specimen of a patient with B cell FL,
      grade 1 in transformation to high grade disease. Tat-1 cells expressed lymphoid
      markers and developed tumor masses in immunodeficient mice. Bcl-2, Bcl-X(L), Bax
      and p53 protein expression was revealed by Western blotting. Flow cytometric
      analysis confirmed P-gp expression. Cytogenetically, the Tat-1 cell line showed
      identical chromosomal alterations to that of the initial biopsy specimen, among
      which the most notable were the t(14;18) typical of FL and additional
      abnormalities involving chromosomes 1, 8 and 13. Multicolor FISH analysis
      delineated all abnormalities, including a t(1p;8q), a der(8)(8q24::14q32::18q21)
      and a der(13)(13q32::8q24::14q32::18q21). Further FISH investigations using a
      locus-specific probe cocktail containing c-myc, IgH and bcl-2 revealed fusion of
      these three loci on the derivatives 8 and 13, in addition to the derivative 14
      IgH/bcl-2 fusion and an extra copy of c-myc on derivative chromosome 1. These
      results demonstrate an additional example of the deregulation of bcl-2 and c-myc
      expression through recombination with a single IgH enhancer region. The unusual
      molecular features of the Tat-1 cell line render it a unique tool for studies
      focused on cytogenetic alterations, expression of multidrug resistance phenotype
      and expression of anti-apoptotic proteins in FL.

PMID- 11840296
TI  - Elimination of mycoplasma from leukemia-lymphoma cell lines using antibiotics.
AB  - Mycoplasmal contamination of cell culture systems continues to present major
      problems for basic research and for manufacturing of bioproducts. Previous work
      suggested that certain antibiotics have strong anti-mycoplasma properties and
      raised the prospect that the technically rather simple antibiotic treatment may
      be an appropriate means for mycoplasma eradication. We have developed and
      validated an effective strategy to eliminate mycoplasma from chronically infected
      cell cultures using antibiotics which have shown strong activity against these
      contaminants. Here, we describe our experience with the treatment of 123
      consecutive mycoplasma-positive leukemia-lymphoma cell lines, comparing five
      different antibiotic regimens (in total 433 treatments). We optimized the
      antibiotic dose schedules and the duration of treatments. The various antibiotic
      treatments which were employed in parallel had a high efficacy, as 71% to 86% of
      the infected cultures were cleansed. Treatment failure may result from the
      resistance of the mycoplasmas to antibiotic therapy and the inability of the
      eukaryotic cells to survive the cytotoxic effects of the antibiotics. Resistance
      to mycoplasma eradication was observed in 3% to 20% of the cultures. Loss of the
      cell culture caused by cytotoxicity was seen in 3% to 11% of the treatments. With
      regard to the overall outcome, 96% of the cell lines were rendered mycoplasma
      free with at least one of the antibiotic treatments and were permanently cured.
      In conclusion, antibiotic treatment represents the most practical and efficient
      option to cleanse mycoplasma-positive cell lines.

PMID- 11840297
TI  - Detection of mycoplasma in leukemia-lymphoma cell lines using polymerase chain
      reaction.
AB  - The specific, sensitive and reliable detection of mycoplasma contamination in
      cell cultures is an important part of mycoplasma control. We have sought to
      develop and validate a method for mycoplasma detection which is sensitive and
      accurate, but also practical in the sense of time spent, costs, and applicability
      in the standard laboratory; finally, the method should be suitable for screening
      large numbers of test specimens. To that end, we adapted a previously developed
      polymerase chain reaction (PCR) method for daily routine application. This single
      step PCR uses a mixture of primers annealing to gene sequences coding for
      evolutionarily conserved 16S rRNA of different mycoplasma species, including the
      ones most commonly found in cell cultures. An internal control was introduced to
      exclude any false-negative tests resulting from technical PCR problems. This
      mycoplasma detection by PCR has been validated prospectively on 201 consecutive
      leukemia-lymphoma cell lines received at the institute over a 3-year period and
      on 118 initially positive cell lines after anti-mycoplasma treatment with
      antibiotics. The sensitivity (detection of true positives) of this PCR detection
      assay was 96% and the specificity (detection of true negatives) was also 96%,
      with positive and negative predictive values (probability of correct result) of
      86% and 99%, respectively. PCR defined the mycoplasma status with 96% accuracy
      (detection of true positives and true negatives). Besides the high sensitivity
      and specificity, further attractive features of the PCR approach are the ease and
      speed with which large numbers of specimens can be tested. PCR mycoplasma
      analysis provides a readily available, quick and reliable test system with which
      to manage the important issue of mycoplasma contamination of cell lines.

PMID- 11840298
TI  - Detection of dual TEL-ABL transcripts and a Tel-Abl protein containing
      phosphotyrosine in a chronic myeloid leukemia patient.

PMID- 11840300
TI  - Gene-environment interactions in Molecular Psychiatry.

PMID- 11840299
TI  - Risks among siblings and twins for childhood acute lymphoid leukaemia: results
      from the Swedish Family-Cancer Database.

PMID- 11840303
TI  - A possible role of olivary gap-junctions in the generation of physiological and
      pathological tremors.

PMID- 11840304
TI  - Role of apoE/Abeta interactions in Alzheimer's disease: insights from transgenic
      mouse models.

PMID- 11840305
TI  - Association between the BDNF 196 A/G polymorphism and sporadic Alzheimer's
      disease.

PMID- 11840306
TI  - Age and the relationship of dopamine D3, serotonin 2C and serotonin 2A receptor
      genes to abnormal involuntary movements in chronic schizophrenia.

PMID- 11840307
TI  - Thyroid hormones, serotonin and mood: of synergy and significance in the adult
      brain.
AB  - The use of thyroid hormones as an effective adjunct treatment for affective
      disorders has been studied over the past three decades and has been confirmed
      repeatedly. Interaction of the thyroid and monoamine neurotransmitter systems has
      been suggested as a potential underlying mechanism of action. While catecholamine
      and thyroid interrelationships have been reviewed in detail, the serotonin system
      has been relatively neglected. Thus, the goal of this article is to review the
      literature on the relationships between thyroid hormones and the brain serotonin
      (5-HT) system, limited to studies in adult humans and adult animals. In humans,
      neuroendocrine challenge studies in hypothyroid patients have shown a reduced 5
      HT responsiveness that is reversible with thyroid replacement therapy. In adult
      animals with experimentally-induced hypothyroid states, increased 5-HT turnover
      in the brainstem is consistently reported while decreased cortical 5-HT
      concentrations and 5-HT2A receptor density are less frequently observed. In the
      majority of studies, the effects of thyroid hormone administration in animals
      with experimentally-induced hypothyroid states include an increase in cortical 5
      HT concentrations and a desensitization of autoinhibitory 5-HT1A receptors in the
      raphe area, resulting in disinhibition of cortical and hippocampal 5-HT release.
      Furthermore, there is some indication that thyroid hormones may increase cortical
      5-HT2 receptor sensitivity. In conclusion, there is robust evidence, particularly
      from animal studies, that the thyroid economy has a modulating impact on the
      brain serotonin system. Thus it is postulated that one mechanism, among others,
      through which exogenous thyroid hormones may exert their modulatory effects in
      affective illness is via an increase in serotonergic neurotransmission,
      specifically by reducing the sensitivity of 5-HT1A autoreceptors in the raphe
      area, and by increasing 5-HT2 receptor sensitivity.

PMID- 11840308
TI  - Comparative analysis of group II metabotropic glutamate receptor immunoreactivity
      in Brodmann's area 46 of the dorsolateral prefrontal cortex from patients with
      schizophrenia and normal subjects.
AB  - Glutamate is the primary excitatory neurotransmitter in the mammalian central
      nervous system, and a key neurotransmitter in prefrontal cortical function.
      Converging lines of evidence implicate prefrontal cortical dysfunction in the
      neurobiology of schizophrenia. Thus, aberrant glutamate neurotransmission may
      underlie schizophrenia and other complex disorders of behavior. Group II
      metabotropic receptors (mGluRs) are important modulators of glutamatergic and non
      glutamatergic neurotransmission. Moreover, in an animal model, an agonist for
      group II mGluRs has been shown to reverse the behavioral, locomotor, and
      cognitive effects of the psychotomimetic drug phencyclidine. Accordingly, group
      II mGluRs constitute attractive targets for the pharmacotherapeutics and study of
      schizophrenia. Using immunocytochemistry and Western immunoblotting, we compared
      the localization and levels of group II mGluRs in Brodmann's area 46 of the
      dorsolateral prefrontal cortex from patients with schizophrenia and normal
      subjects. Consistent with previous reports, we found that immunolabeling of group
      II mGluRs is prominent in Brodmann's area 46. The majority of labeling was
      present on axon terminals distributed in a lamina-specific fashion. No apparent
      difference in the cellular localization or laminar distribution of immunoreactive
      group II mGluRs was noted between the two diagnostic groups. Similarly, the
      levels of receptor immunoreactivity determined by quantitative Western
      immunoblotting were comparable between schizophrenic patients and normal
      subjects. We conclude that while the function of group II mGluRs in Brodmann's
      area 46 of dorsolateral prefrontal cortex may be altered in patients with
      schizophrenia, this is not evident at the level of protein expression using an
      antibody against mGluR2 and mGluR3.

PMID- 11840309
TI  - Segmental linkage disequilibrium within the dopamine transporter gene.
AB  - The dopamine transporter gene (DAT) has been implicated in a variety of
      disorders, including bipolar disorder, attention-deficit hyperactivity disorder,
      cocaine-induced paranoia, Tourette's syndrome, and Parkinson's disease. As no
      clear functional polymorphism has been identified to date, studies rely on
      linkage disequilibrium (LD) to assess the possible genetic contribution of DAT to
      the various disorders. A better understanding of the complex structure of LD
      across the gene is thus critical for an accurate interpretation of the results of
      such studies, and may facilitate the mapping of the actual functional variants.
      In the process of characterizing the extent of variation within the DAT gene, we
      have identified a number of single nucleotide polymorphisms (SNPs) suitable for
      LD studies, 14 of which have been analyzed, along with a 3' repeat polymorphism,
      in a sample of 120 parent-proband triads. Calculations of pairwise LD between the
      SNPs in the parental haplotypes revealed a high degree of LD (P < 0.00001) in the
      5' (distal promoter through intron 6) and 3' (exon 9 through exon 15) regions of
      DAT. This segmental LD pattern is maintained over approximately 27 kb and 20 kb
      in these two regions, respectively, with very little significant LD between them,
      possibly due to the presence of a recombination hotspot located near the middle
      of the gene. These analyses of the DAT gene thus reveal a complex structure
      resulting from both recombination and mutation, knowledge of which may be
      invaluable to the design of future studies.

PMID- 11840311
TI  - In vitro biotransformation of the selective serotonin reuptake inhibitor
      citalopram, its enantiomers and demethylated metabolites by monoamine oxidase in
      rat and human brain preparations.
AB  - This study was conducted to identify enzyme systems eventually catalysing a local
      cerebral metabolism of citalopram, a widely used antidepressant of the selective
      serotonin reuptake inhibitor type. The metabolism of citalopram, of its
      enantiomers and demethylated metabolites was investigated in rat brain microsomes
      and in rat and human brain mitochondria. No cytochrome P-450 mediated
      transformation was observed in rat brain. By analysing H2O2 formation, monoamine
      oxidase A activity in rat brain mitochondria could be measured. In rat whole
      brain and in human frontal cortex, putamen, cerebellum and white matter of five
      brains monoamine oxidase activity was determined by the stereoselective
      measurement of the production of citalopram propionate. All substrates were
      metabolised by both forms of MAO, except in rat brain, where monoamine oxidase B
      activity could not be detected. Apparent Km and Vmax of S-citalopram
      biotransformation in human frontal cortex by monoamine oxidase B were found to be
      266 microM and 6.0 pmol min(-1) mg(-1) protein and by monoamine oxidase A 856
      microM and 6.4 pmol min(-1) mg(-1) protein, respectively. These Km values are in
      the same range as those for serotonin and dopamine metabolism by monoamine
      oxidases. Thus, the biotransformation of citalopram in the rat and human brain
      occurs mainly through monoamine oxidases and not, as in the liver, through
      cytochrome P-450.

PMID- 11840310
TI  - Epi-inositol regulates expression of the yeast INO1 gene encoding inositol-1-P
      synthase.
AB  - Myo-inositol exerts behavioral effects in animal models of psychiatric disorders
      and is effective in clinical trials in psychiatric patients. Interestingly, epi
      inositol exerts behavioral effects similar to myo-inositol, even though epi
      inositol is not a substrate for synthesis of phosphatidylinositol. We postulated
      that the behavioral effects of epi-inositol may be due to its effects on gene
      expression. Yeast INO1expression was measured in northern blots. INM1 was
      determined by beta-galactosidase activity in a strain containing the fusion gene
      INM1-lacZintegrated into the genome. Epi-inositol affects regulation of
      expression of the INO1 gene (encoding inositol-1-P synthase), even though it
      cannot support growth of an inositol auxotroph (suggesting that, as in mammalian
      cells, it is not incorporated into phosphatidylinositol). Like myo-inositol,
      although to a lesser extent, epi-inositol causes a significant reduction in INO1
      expression, and reverses the lithium- or valproate-induced increase in INO1
      expression. However, it does not affect regulation of INM1 (encoding inositol
      monophosphatase), the expression of which is up-regulated by myo-inositol. The
      observed regulatory effects of epi-inositol on expression of the most highly
      regulated gene in the inositol biosynthetic pathway may help to explain how this
      inositol isomer can exert behavioral effects without being incorporated into
      phosphatidylinositol.

PMID- 11840312
TI  - The Wellcome trust UK-Irish bipolar affective disorder sibling-pair genome
      screen: first stage report.
AB  - We have completed the first stage of a two-stage genome wide screen designed to
      identify chromosomal regions that may harbour susceptibility genes for bipolar
      affective disorder. The first stage screening sample included 509 subjects from
      151 nuclear families recruited within the United Kingdom and Republic of Ireland.
      This sample contained 154 narrowly defined affected sibling pairs (DSM-IV BPI)
      and 258 broadly defined affected sibling pairs (DSM-IV BPI, SABP, BPII, BPNOS or
      MDD(R)), approximately two thirds of all families contained at least one other
      additional typed individual. All individuals were genotyped using 398 highly
      polymorphic microsatellite markers from Applied Biosystems's Linkage Mapping Set
      Version 2. The average inter-marker distance was 9.6 cM and the mean
      heterozygosity was 0.78. Analysis of these data using non-parametric linkage
      methods (MAPMAKER/SIBS) found no evidence for loci of major effect and no regions
      reached genome-wide significance for either suggestive or significant linkage. We
      identified 19 points across the genome where the MLS exceeded a value set for
      follow up in our second stage screen (MLS > or = 0.74 (equivalent to a nominal
      pointwise significance of 5%) under the narrowest diagnostic model). These points
      were on chromosomes 2, 3, 4, 6, 7, 9, 10, 12, 17, 18 & X. Some of these points
      overlapped with previous linkage reports both within bipolar affective disorder
      and other psychiatric illnesses. Under the narrowest diagnostic model, the single
      most significant multipoint linkage was on chromosome 18 at marker D18S452
      (MLS=1.54). Overall the highest MLS was 1.70 on chromosome 2 at marker D2S125,
      under the broadest diagnostic model.

PMID- 11840314
TI  - cAMP signaling pathway in depressed patients with psychotic features.
AB  - Abnormalities in protein kinase A (PKA) and Rap1 have recently been reported in
      depressed patients. The aim of the present study was to investigate the levels of
      these proteins in platelets from untreated unipolar and bipolar depressed
      patients with psychotic features. The levels PKA and Rap1 were assessed by
      Western blot analysis and immunostaining in 37 drug-free patients and 29 healthy
      subjects. Both unipolar and bipolar patients with psychotic depression have
      significantly lower levels of platelet regulatory type I and higher levels of
      catalytic subunits of PKA than controls, whereas the levels of regulatory type II
      were higher only in psychotic unipolar patients. No significant differences were
      found in the immunolabeling of both Rap1 and actin among groups. These findings
      support the idea that besides nonpsychotic depression, abnormalities of PKA could
      be linked, albeit in a somewhat different way, with psychotic depression.

PMID- 11840313
TI  - Excess of allele1 for alpha3 subunit GABA receptor gene (GABRA3) in bipolar
      patients: a multicentric association study.
AB  - The available data from preclinical and pharmacological studies on the role of
      gamma amino butyric acid (GABA) support the hypothesis that a dysfunction in
      brain GABAergic system activity contributes to the vulnerability to bipolar
      affective disorders (BPAD). Moreover, the localization of the alpha3 subunit GABA
      receptor GABRA3 gene on the Xq28, a region of interest in certain forms of
      bipolar illness, suggests that GABRA3 may be a candidate gene in BPAD. In the
      present study, we tested the genetic contribution of the GABRA3 dinucleotide
      polymorphism in a European multicentric case-control sample, matched for sex and
      ethnogeographical origin. Allele and genotype (in females) frequencies were
      compared in 185 BPAD patients and 370 controls. A significant increase of
      genotype 1-1 was observed in BPAD females compared to controls (P=0.0004).
      Furthermore, when considering recessivity of allele 1 (females with genotype 1-1
      and males carrying allele 1), results were even more significant (P= 0.00002).
      Our findings suggest that the GABRA3 polymorphism may confer susceptibility to or
      may be in linkage disequilibrium with another gene involved in the genetic
      etiology of BPAD.

PMID- 11840315
TI  - Association between a serotonin transporter promoter region polymorphism and mood
      response during tryptophan depletion.
AB  - This study investigated the relationship between depressive symptom response
      during tryptophan (TRP) depletion and a functional polymorphism of the promoter
      region of the serotonin (5-HT) transporter gene (SLC6A4).(1) Forty-three subjects
      in remission from a major depressive episode who underwent TRP depletion were
      genotyped. DNA was extracted from blood lymphocytes or from cheek cells.(2) The
      two common alleles are designated long (l) and short (s). Depressive symptoms
      were measured with the 25-item Hamilton Depression Rating Scale (HDRS).(3) There
      was a significant association between the l homozygous genotype and the
      depressive response to TRP depletion, with a significant main effect of time (F =
      8.763, df = 3, 38, P = <0.001), and time x l homozygous allele interaction (F =
      3.676, df = 3, 38, P = 0.02). Individuals whose genotype predicted increased 5-HT
      transporter activity may be more susceptible to depressive changes in response to
      transient 5-HT perturbations. The use of endophenotypic markers for affective
      disorders such as the mood response to TRP depletion may facilitate studies of
      complex genetic traits such as depression by decreasing its heterogeneity.

PMID- 11840317
TI  - Exclusion of the neuronal nicotinic acetylcholine receptor alpha7 subunit gene as
      a candidate for catatonic schizophrenia in a large family supporting the
      chromosome 15q13-22 locus.
AB  - The gene encoding the neuronal nicotinic acetylcholine receptor alpha7 subunit
      (CHRNA7) is located on chromosome 15q13.2. This region was suggested to be
      involved in the etiopathogenesis of: (a) schizophrenia combined with a
      neurophysiological deficit; (b) lithium-responsive bipolar disorder; and (c)
      familial catatonic schizophrenia (periodic catatonia). Therefore, members of a
      large family with periodic catatonia strongly supporting the chromosome 15q13-22
      region were genotyped with polymorphic markers localized around the CHRNA7 locus.
      A recombination event distally of marker D15S144 leading to the exclusion of the
      CHRNA7 locus from this candidate region was detected in one branch of the
      pedigree. This result provides strong evidence that a gene located telomeric to
      CHRNA7 is causative for the pathogenesis of catatonic schizophrenia in this
      family.

PMID- 11840316
TI  - Y chromosome haplogroups in autistic subjects.
AB  - The male to female ratio in autism is 4:1 in the global autistic population, but
      increases to 23:1 in autistic subjects without physical or brain
      abnormalities.(1) Despite this well-recognised gender difference, male
      predisposition to autistic disorder remains unexplained and the role of sex
      chromosomes is still debated. Numerical and structural abnormalities of the sex
      chromosomes are among the most frequently reported chromosomal disorders
      associated with autism. However, genome scans have failed to detect linkage on
      the X chromosome(2,3,4) and this approach cannot study the non-recombining region
      of the Y chromosome. In this study, we searched for a specific Y chromosome
      effect in autistic subjects. Using informative Y-polymorphic markers, the Y
      chromosome haplotypes of 111 autistic subjects from France, Sweden and Norway
      were defined and compared with relevant control populations. No significant
      difference in Y-haplotype distribution between the affected and control groups
      was observed. Although this study cannot exclude the presence of a Y
      susceptibility gene, our results are not suggestive of a Y chromosome effect in
      autism.

PMID- 11840318
TI  - A functional polymorphism within the mu-opioid receptor gene and risk for abuse
      of alcohol and other substances.
AB  - Genetic association studies investigating the role of the +118A allele of the
      human mu-opioid receptor gene in risk for alcohol dependency have produced
      inconsistent findings, possibly because of the failure to recognize sampling
      methodology difficulties inherent in association studies of polygenic disorders.
      We examined the frequency of the AA genotype and A allele in several groups of
      substance-dependent cases, unrestricted controls, and super controls screened for
      the use of alcohol and cigarettes. Our findings and analyses suggest that the
      OPRM1 +118 polymorphism is a general risk gene for substance dependence, but is
      not specific to a particular substance. The nature of the conferred risk is
      likely to be in use of multiple substances, but it is not yet determined if the
      risk could be expressed in severity of use of any particular substance. The
      contribution of the gene to risk for substance dependence is small, and is
      detected most easily in studies that use control samples that are screened for
      all forms of substance dependence.

PMID- 11840321
TI  - Id and development.
AB  - During development, it is obvious that enormous multiplication and
      diversification of cells is required to build a body plan from a single
      fertilized egg and that these two processes, proliferation and differentiation,
      must be coordinated properly. Id proteins, negative regulators of basic helix
      loop-helix transcription factors, possess the ability to inhibit differentiation
      and to stimulate proliferation, and are useful molecules for investigating the
      mechanisms regulating development. In the past few years, our understanding of
      the roles of Id proteins has been substantially enhanced by the detailed
      investigation of genetically modified animals. The data have indicated that the
      functions of Id proteins in vivo are functionally related to those revealed by
      earlier work in cell culture systems. However, unexpected organs and cell types
      have also been found to require Id proteins for their normal development. This
      review looks at the advances made in our understanding of the in vivo functions
      of Id proteins. The topics discussed include neurogenesis, natural killer cell
      development, lymphoid organogenesis, mammary gland development and
      spermatogenesis.

PMID- 11840322
TI  - Emc, a negative HLH regulator with multiple functions in Drosophila development.
AB  - Expression and functional analyses of Emc have demonstrated that it is a
      prototype for a protein required for multiple processes in development. Initially
      characterized as a negative regulator of sensory organ development, it was later
      found to regulate many other developmental processes and cell proliferation. Its
      ability to block the function of bHLH proteins by forming heterodimers, which are
      ineffective in DNA binding, accounts for the role of Emc in preventing the
      acquisition of several cell fates which are under the control of bHLH proteins.
      However, while maintaining this repressive molecular mechanism, emc also appears
      to act as a positive regulator of differentiation.

PMID- 11840323
TI  - The regulation and function of the Id proteins in lymphocyte development.
AB  - Helix-loop-helix (HLH) proteins are essential factors for lymphocyte development
      and function. One class of HLH proteins, the E-proteins, regulate many aspects of
      lymphocyte maturation, survival, proliferation, and differentiation. E-proteins
      are negatively regulated by another class of HLH proteins known as the Id
      proteins. The Id proteins function as dominant negative inhibitors of E-proteins
      by inhibiting their ability to bind DNA. Here we discuss the function and
      regulation of the Id proteins in lymphocyte development.

PMID- 11840324
TI  - Id proteins in cell cycle control and cellular senescence.
AB  - The Id family of helix-loop-helix (HLH) proteins are thought to affect the
      balance between cell growth and differentiation by negatively regulating the
      function of basic-helix-loop-helix (bHLH) transcription factors. Although it has
      been suggested for some time that Id is involved in cell cycle regulation, little
      is known about the molecular mechanism of this control. Recent studies, however,
      have revealed that Id binds to important cell cycle regulatory proteins other
      than bHLH proteins. Two such proteins, pRB (retinoblastoma tumour suppressor
      protein) family proteins and Ets-family transcription factors are known to play
      key roles in cell cycle regulation, transformation and tumour suppression.
      Through the characterization of these pathways we will begin to understand the
      mechanisms by which Id controls normal and abnormal cell cycle progression.

PMID- 11840325
TI  - Id proteins at the cross-road of development and cancer.
AB  - A large body of evidence has been accumulated that demonstrates dominant effects
      of Id proteins on different aspects of cellular growth. Generally, constitutive
      expression of Id not only blocks cell differentiation but also drives
      proliferation. In some settings, it is sufficient to render cells immortal or
      induce oncogenic transformation. The participation of Id proteins in advanced
      human malignancy, where they are frequently deregulated, has been dramatically
      bolstered by the recent discovery that Id exert pivotal contributions to many of
      the essential alterations that collectively dictate malignant growth. Relentless
      proliferation associated with self-sufficiency in growth signals and
      insensitivity to growth inhibitory signals, sustained neoangiogenesis, tissue
      invasiveness and migration capabilities of tumor cells all share dependency on
      the unlimited availability of Id proteins. It is remarkable that many of these
      features recapitulate those physiologically propelled by Id proteins to support
      normal development. We propose that the participation of Id in multiple
      fundamental traits of cancer may be the basis for unprecedented therapeutic
      opportunities.

PMID- 11840326
TI  - The Id proteins and angiogenesis.
AB  - Since the identification of the Id proteins over a decade ago, a great many cell
      cycle and cell fate decisions have been shown to be under the control of these
      proteins as described in other sections of this review issue. Perhaps the most
      unsuspected activity of this class of proteins has been their essential role in
      angiogenesis, both in the forebrain during development and during the growth and
      metastasis of tumors in adults. This section of the review issue will focus on
      the key observations which have led to these conclusions, speculations about
      potential mechanisms and the outlook for potential therapeutic interventions.

PMID- 11840327
TI  - Vertebrate hairy and Enhancer of split related proteins: transcriptional
      repressors regulating cellular differentiation and embryonic patterning.
AB  - The basic-helix-loop-helix (bHLH) proteins are a superfamily of DNA-binding
      transcription factors that regulate numerous biological processes in both
      invertebrates and vertebrates. One family of bHLH transcriptional repressors is
      related to the Drosophila hairy and Enhancer-of-split proteins. These repressors
      contain a tandem arrangement of the bHLH domain and an adjacent sequence known as
      the Orange domain, so we refer to these proteins as bHLH-Orange or bHLH-O
      proteins. Phylogenetic analysis reveals the existence of four bHLH-O subfamilies,
      with distinct, evolutionarily conserved features. A principal function of bHLH-O
      proteins is to bind to specific DNA sequences and recruit transcriptional
      corepressors to inhibit target gene expression. However, it is likely that bHLH-O
      proteins repress transcription by additional mechanisms as well. Many vertebrate
      bHLH-O proteins are effectors of the Notch signaling pathway, and bHLH-O proteins
      are involved in regulating neurogenesis, vasculogenesis, mesoderm segmentation,
      myogenesis, and T lymphocyte development. In this review, we discuss mechanisms
      of action and biological roles for the vertebrate bHLH-O proteins, as well as
      some of the unresolved questions about the functions and regulation of these
      proteins during development and in human disease.

PMID- 11840330
TI  - HER2/Neu: mechanisms of dimerization/oligomerization.
AB  - DOI: 10.1038/sj/onc/1205119

PMID- 11840331
TI  - RB18A regulates p53-dependent apoptosis.
AB  - We previously demonstrated that RB18A, a member of TRAP220/DRIP205/PBP family, in
      vivo acted as a cofactor of transcription by differently regulating p53wt
      transactivating activity on physiological promoters. Using p53-negative cells
      transfected with different constructs, we herein demonstrated that RB18A down
      regulated p53wt-dependent apoptosis. This biological regulation was due to a
      specific diminution of p53wt protein level, as level of p53mut and GAPDH proteins
      was not modified. This p53wt diminution was dependent on proteasome activity, as
      inhibited by MG-132 inhibitor. This specific p53wt degradation was correlated
      with an increase in expression of MDM2, which promoted p53wt degradation into
      proteasome. RB18A up-regulated MDM2 expression by activating MDM2 promoter, even
      in absence of p53wt. Altogether, these data emphasized that RB18A could regulate
      p53wt function not only by direct interaction between both proteins, but also by
      up-regulating promoter activity of MDM2, a p53-regulating partner.

PMID- 11840332
TI  - MDMX stability is regulated by p53-induced caspase cleavage in NIH3T3 mouse
      fibroblasts.
AB  - MDMX is a p53 binding protein, which shares a high degree of homology with MDM2,
      a negative regulator of the tumor suppressor p53. MDMX has been shown to
      counteract MDM2-dependent p53 degradation and to stabilize p53 in its inactive
      form. In this study: we identify two MDMX proteolytic pathways that control its
      intracellular levels, and show that MDMX post-translational processing may be
      regulated by p53. Mouse MDMX is cleaved in vitro and in vivo by caspase activity,
      between aminoacids 358 and 361, producing a p54 minor form. In addition, MDMX is
      subjected to proteasome-mediated degradation, which concurs to MDMX proteolysis
      mainly through degradation of p54. A D361A-MDMX mutant, resistant to caspase
      cleavage, exhibits prolonged intracellular lifetime in comparison to wild-type
      protein, indicating that caspase cleavage affects stability of MDMX protein
      probably by modulating its further degradation. Overexpression of exogenous p53
      increases the intracellular levels of p54 product. Similarly, activation of
      endogenous p53 by adriamycin enhances MDMX cleavage and produces a marked
      decrease of its intracellular levels, while not affecting the D361A-MDMX mutant.
      In addition, the D361A-MDMX mutant lacks the ability to inhibit p53
      transactivation in respect to wild-type MDMX, suggesting that MDMX caspase
      cleavage play an important functional role. In conclusion, our results
      demonstrate that, in analogy to MDM2, MDMX may be subjected to proteolytic
      modifications that regulate its intracellular levels. Moreover, decrease of MDMX
      protein levels following p53 activation suggests a p53-dependent regulatory
      feedback of MDMX function.

PMID- 11840334
TI  - Centrosome abnormalities, recurring deletions of chromosome 4, and genomic
      amplification of HER2/neu define mouse mammary gland adenocarcinomas induced by
      mutant HER2/neu.
AB  - The conditional expression of activated HER2/neu gene under its endogenous
      promoter in the mammary epithelium of the mouse results in accelerated lobular
      development and focal mammary tumors. Carcinogenesis, however, requires
      amplification and considerably increased expression levels of oncogenic neu.
      Deducing from the multiple genetic aberrations required for human breast cancer
      to develop, we hypothesized that in addition to the over-expression of an
      activated HER2/neu, secondary aberrations would occur. We have therefore
      conducted a genomic screen for chromosomal imbalances and translocations using
      comparative genomic hybridization and spectral karyotyping. The results reveal a
      moderate degree of chromosomal instability and micronuclei formation in short
      term cultures established from primary tumors. Genomic instability appears to be
      linked to the amplification of functional centrosomes, a phenomenon that we
      frequently observed in other tumor types. Seventy per cent of the tumors revealed
      genomic amplification of HER2/neu, often in the form of double minute
      chromosomes, which correlated with recurring loss of mouse chromosome 4D-E, a
      region that is orthologous to distal human chromosome 1p. It is likely that this
      region contains putative tumor suppressor genes whose inactivation is required
      for tumor formation in this model of human breast cancer.

PMID- 11840333
TI  - Human Dkk-1, a gene encoding a Wnt antagonist, responds to DNA damage and its
      overexpression sensitizes brain tumor cells to apoptosis following alkylation
      damage of DNA.
AB  - The human Dkk-1 (hDkk-1) gene, a transcriptional target of the p53 tumor
      suppressor, encodes a powerful inhibitor of the Wnt signaling pathway and
      regulates the spatial patterning/morphogenesis of the mammalian central nervous
      system. We investigated the p53-related functions of the hDkk-1 gene by studying
      its response to DNA damage and its modulation of apoptosis in human glioma cells.
      Various chemotherapeutic and other agents that induce DNA adducts and compromise
      its integrity (1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), cisplatin, H(2)O(2)
      and UV rays) enhanced the expression of hDkk-1 significantly. The damage-induced
      increase in hDkk-1 mRNA levels occurred in many human tumor cell lines,
      irrespective of their p53 gene status. The human glioblastoma cell line, U87MG,
      which had undetectable hDkk-1 expression, was engineered to express moderate
      levels of the hDkk protein by stable transfection. The engineered cells did not
      show any morphological changes, but underwent marked apoptosis after ceramide
      treatment. Further, the DNA cross-linking drugs BCNU and cisplatin, but not the
      microtubule poison vincristine, induced significant cell death in U87MG/hDkk
      cells, and this was accompanied by altered Bcl-2/Bax expression and a reduction
      in the amount of telomere DNA as visualized by fluorescence in situ
      hybridization. These results show that hDkk-1 is a pro-apoptotic gene and suggest
      that it may play important roles in linking the oncogenic Wnt and p53 tumor
      suppressor pathways.

PMID- 11840335
TI  - HST-1/FGF-4 gene activation induces spermatogenesis and prevents adriamycin
      induced testicular toxicity.
AB  - We previously demonstrated expression of the HST-1/FGF-4 gene in the testis of
      normal adult animals, which suggests its possible role in spermatogenesis. For an
      understanding of its functional significance in the testis, conditional transgene
      expression was used. Precise genetic switches can be efficiently generated in a
      straightforward manner using adenovirus-carrying Cre recombinase, which means our
      new strategies promise to contribute substantially to a better and prompt
      understanding of the functions of genes in vivo by controlling the expression of
      any gene to any organ at any desired time. Our new method demonstrated for the
      first time that the specific gain of function of the HST-1/FGF-4 gene in the
      testis resulted in markedly enhanced spermatogenesis. To further investigate the
      function and therapeutic potency of HST-1/FGF-4, transgenic mice with enhanced
      HST-1/FGF-4 expression in the testis were exposed to adriamycin (ADR), an
      anticancer drug causing severe testicular toxicity. Degree of damage to
      spermatogenesis was assessed by sperm count, testicular weight, histology, and
      DNA ploidy. Induced expression of HST-1/FGF-4 markedly enhanced the recovery of
      ADR-induced testicular damage. Furthermore, adenoviruses carrying the HST-1/FGF-4
      gene ameliorated testicular toxicity of ADR. These results with new adenovirus
      mediated Cre/lox conditional mice indicated that HST-1/FGF-4 could be an
      important factor for spermatogenesis, presenting a new paradigm to treat impaired
      fertility.

PMID- 11840336
TI  - c-Myc initiates illegitimate replication of the ribonucleotide reductase R2 gene.
AB  - The mechanisms through which the oncoprotein c-Myc initiates locus-specific gene
      amplification are not understood. When analysing the initiation mechanism of c
      Myc-dependent amplification of the mouse ribonucleotide reductase R2 (R2) gene,
      we observe c-Myc-dependent initiation of illegitimate DNA replication of the R2
      gene. We demonstrate multiple simultaneous c-Myc-induced R2 replication forks,
      whereas R2 normally replicates with a single fork. In contrast, cyclin C
      replicates with only a single replication fork irrespective of c-Myc
      deregulation. In addition to de novo replication forks, c-Myc also initiates bi
      allelic replication of R2, abrogating its normal mono-allelic replication
      pattern. Moreover, several chromosomal regions also display c-Myc-induced
      illegitimate replication profiles. Thus, c-Myc can act as an illegitimate
      replication-licensing factor that promotes de novo replication initiation and
      illegitimate replication timing that adversely impacts upon genomic stability.

PMID- 11840337
TI  - Minimal and inducible regulation of tissue factor pathway inhibitor-2 in human
      gliomas.
AB  - Tissue factor pathway inhibitor-2 (TFPI-2), a serine protease inhibitor abundant
      in the extra cellular matrix, is highly expressed in non-invasive cells but
      undetectable levels in highly invasive human glioma cells. The mechanisms
      responsible for its transcriptional regulation are not well elucidated. In this
      study, we made several deletion constructs from a 3.6 kb genomic fragment from
      Hs683 cells containing the 5'-flanking region of the TFPI-2 gene, transiently
      transfected with these constructs into non-invasive (Hs683) and highly invasive
      (SNB19) human glioma cells, and assessed their expression by using a luciferase
      reporter gene. Three constructs showed high promoter activity (pTF5, -670 to +1;
      pTF6, -312 to +1; pTF2, -1511 to +1). Another construct, pTF8 (-81 to +1), showed
      no activity. PTF9, a variant of pTF5 in which a further 231 bp fragment (-312 to 
      81) was deleted, from the [-670 to +1] pTF5 region, also showed no promoter
      activity. Hence, (-312 to -81) this region is essential for the transcription of
      TFPI-2 in glioma cells. Sequencing of this promoter region revealed that it has a
      high G+C content, contains potential SP1 and AP1 binding motifs, and lacks
      canonical TATA and CAAT boxes immediately upstream of the major transcriptional
      initiation site, although CAAT boxes were found about -3000 bp upstream of the
      transcription start site. We also found a strong repressor in the region between 
      927 to -1181, upstream of the major transcriptional initiation site, followed by
      positive elements or enhancers between -1511 to -1181. These positive elements
      masked the silencer effect. Finally TFPI-2 was induced in Hs683 cells transfected
      with the pTF6 construct (-312 to +1) and stimulated with phorbol-12-myristate-13
      acetate (PMA). We conclude that the -312 to +1 region is critical for the minimal
      and inducible regulation of TFPI-2 in non-invasive (Hs683) and highly invasive
      (SNB19) human glioma cell lines.

PMID- 11840338
TI  - Serial analysis of gene expression in renal carcinoma cells reveals VHL-dependent
      sensitivity to TNFalpha cytotoxicity.
AB  - We have used serial analysis of gene expression (SAGE) to investigate the
      influence of the von Hippel-Lindau (VHL) gene on global gene expression profiles.
      SAGE libraries were prepared from renal cell carcinoma (RCC) lines that either
      lack (parental) or express wild-type VHL (wtVHL). Comparison of these libraries
      revealed some differentially expressed genes (Glut-1, for example) that were
      known to be influenced by VHL, but the majority of genes had not previously been
      reported to be affected by the cell's VHL status. The identification of several
      genes involved in TNFalpha-mediated events prompted us to compare the sensitivity
      of cells with different VHL status in TNFalpha cytotoxicity assays. Strikingly,
      VHL-deficient cells were much more resistant to the toxic influence of TNFalpha.
      We propose that VHL-dependent sensitization of RCC cells to TNFalpha-mediated
      killing may contribute to VHL's growth suppressive function.

PMID- 11840339
TI  - Regulation of choline kinase activity by Ras proteins involves Ral-GDS and PI3K.
AB  - Ras proteins are molecular switches that control signaling pathways critical in
      the onset of a variety of human cancers. The signaling pathways activated by Ras
      proteins are those controlled by its direct effectors such as the serine
      threonine protein kinase Raf-1, the exchange factor for other GTPases Ral-GDS,
      and the lipid kinase PI3K. As a consequence of Ras activation, a number of
      additional enzymes are affected, including several members of the serine
      threonine intracellular proteins kinases as well as enzymes related to
      phospholipid metabolism regulation such as phospholipases A2 and D, and choline
      kinase. The precise mechanisms by which ras oncogenes impinge into these later
      molecules and their relevance to the onset of the carcinogenic process is still
      not fully understood. Here we have investigated the mechanism of regulation of
      choline kinase by Ras proteins and found no direct link between PLD and choline
      kinase activation. We provide evidence that Ras proteins regulate the activity of
      choline kinase through its direct effectors Ral-GDS and PI3K, while the Raf
      pathways seems to be not relevant in this process. The importance of Ras
      dependent activation of choline kinase is discussed.

PMID- 11840340
TI  - The human papillomavirus type 16 (HPV-16) E5 protein sensitizes human
      keratinocytes to apoptosis induced by osmotic stress.
AB  - We have studied the role of the HPV-16 E5 protein in apoptosis, using HaCaT cell
      lines stably transfected with either E5 (HaCaT/E5) or the empty vector
      (HaCaT/pMSG) as control. When subjected to a hyperosmolar concentration of
      sorbitol, HaCaT/E5 cells respond with cytochrome c release, activation of caspase
      3, -8, and -9, and PARP-cleavage, showing that the mitochondria and death
      receptor mediated apoptotic pathways are involved in subsequent cell death.
      Similar effects are observed for the control cells only after extended sorbitol
      treatment. Thus, E5-expressing cells are more sensitive to osmotic stress,
      perhaps because of modifications of the cellular membranes caused by this
      strongly hydrophobic molecule.

PMID- 11840341
TI  - Werner and Bloom helicases are involved in DNA repair in a complementary fashion.
AB  - Werner syndrome (WS) is a recessive disorder characterized by premature
      senescence. Bloom syndrome (BS) is a recessive disorder characterized by short
      stature and immunodeficiency. A common characteristic of both syndromes is
      genomic instability leading to tumorigenesis. WRN and BLM genes causing WS and
      BS, encode proteins that are closely related to the RecQ helicase. We produced
      WRN-/-, BLM-/- and WRN(-/-)/BLM(-/-) mutants in the chicken B-cell line DT40. WRN
      /- cells showed hypersensitivities to genotoxic agents, such as 4-nitroquinoline
      1-oxide, camptothecin and methyl methanesulfonate. They also showed a threefold
      increase in targeted integration rate of exogenous DNAs, but not in sister
      chromatid exchange (SCE) frequency. BLM-/- cells showed hypersensitivities to the
      genotoxic agents as well as ultraviolet (UV) light, in addition to a 10-fold
      increase in targeted integration rate and an 11-fold increase in SCE frequency.
      In WRN(-/-)/BLM(-/-) cells, synergistically increased hypersensitivities to the
      genotoxic agents were observed whereas both SCE frequencies and targeted
      integration rates were partially diminished compared to the single mutants.
      Chromosomal aberrations were also synergistically increased in WRN(-/-)/BLM(-/-)
      cells when irradiated with UV light in late S to G(2) phases. These results
      suggest that both WRN and BLM may be involved in DNA repair in a complementary
      fashion.

PMID- 11840342
TI  - Expression and regulation of Cyr61 in human breast cancer cell lines.
AB  - We have shown that Cyr61, an angiogenic regulator, is overexpressed in invasive
      and metastatic human breast cancer cells and tumor biopsies. We have further
      demonstrated that Cyr61 promotes acquisition of estrogen-independence and anti
      estrogen resistance in vivo in breast cancer cells. Moreover, we have
      demonstrated that Cyr61 induces tumor formation and tumor vascularization in
      vivo, events mediated through the activation of the MAPK and the Akt signaling
      pathways. Here we investigate how Cyr61 expression is regulated in both estrogen
      receptor (ER)-positive and ER-negative breast cancer cells. We demonstrate that
      Cyr61 mRNA and protein expression is inducible by estrogen and anti-estrogens in
      ER-positive breast cancer cells. We show that a labile protein as well as a
      negative regulator might be involved in Cyr61 expression in estrogen-dependent
      breast cancer cells. Other important regulators of Cyr61 expression in breast
      cancer cells that we found are the phorbol ester TPA, vitamin D, and retinoic
      acid. TPA causes positive regulation of Cyr61 expression in ER-positive MCF-7
      cells. Vitamin D induces a transient stimulatory effect on Cyr61 gene expression.
      Lastly, retinoic acid has a negative effect on Cyr61 expression and downregulates
      its expression in MCF-7 cells. Interestingly, most of these effects are not seen
      in aggressive breast cancer cells that do not express ER and express high levels
      of Cyr61, such as the MDA-MB-231 cells. Our results are in agreement with our
      knowledge that Cyr61 promotes tumor growth, and that tumor-promoting agents have
      a positive impact on cells that express low levels of Cyr61, such as the ER
      positive breast cancer cells; however, these agents have no significant effect on
      cells that express high levels of Cyr61. Our findings suggest an association
      between increased Cyr61 expression and an aggressive phenotype of breast cancer
      cells.

PMID- 11840344
TI  - Corneal stimulation of MMP-1, -9 and uPA by platelet-activating factor is
      mediated by cyclooxygenase-2 metabolites.
AB  - PURPOSE: This study was undertaken to evaluate the significance of cyclooxygenase
      2 (COX-2) activity on urokinase plasminogen activator (uPA) and matrix
      metalloproteinases (MMPs)-1 and -9 induction in cornea following platelet
      activating factor (PAF) treatment. METHODS: Corneal organ cultures were pre
      treated with increasing concentrations of COX-2-specific inhibitors NS398 or
      nimesulide prior to PAF stimulation. To determine the effect of exogenous
      prostaglandins (PGs) on uPA, MMP-1 and MMP-9 levels, corneas were pre-treated
      with COX-2 inhibitors followed by the addition of 2.5 microM PGD2, PGE2 or
      PGF2alpha. The levels of uPA and MMP-9 were assayed by casein and gelatin
      zymography, respectively. MMP-1 levels were determined by Western Blot analysis.
      RESULTS: The increase in uPA, MMP-9 and MMP-1 levels detected in corneal organ
      cultures treated with 100 nM cPAF was blocked by 5 microM NS398 and 10 microM
      nimesulide, concentrations at which these inhibitors selectively inhibit COX-2
      activity. Furthermore, pre-incubation with COX-2 inhibitors, followed by
      supplementation with PGD2, PGE2 or PGF 2alpha, increases uPA, MMP-9 and MMP-1
      levels in corneas similar to and in some cases greater than that produced by cPAF
      treatment alone. CONCLUSIONS: During corneal injury and inflamation, PAF is an
      important factor in the activation of proteolytic cascades, which could lead to
      corneal epithelial defects and ultimately ulceration. One important goal in
      treating these defects is to modulate the activity of enzymes that destroy the
      extracellular matrix. Our results suggest that COX-2 induction following PAF
      stimulation and subsequent eicosanoid release may play a crucial role in the
      induction of uPA, MMP-1 and MMP-9 enzymes. Specific COX-2 inhibition could
      therefore block the actions of PAF when inflammation is sustained.

PMID- 11840343
TI  - Regulation of p73 by c-Abl through the p38 MAP kinase pathway.
AB  - p73 is a novel member of the p53 family of tumor suppressor proteins which is
      involved in cellular differentiation, tumor suppression, and the response to
      genotoxic stress. The molecular mechanisms regulating p73 activity are still
      poorly understood. Recently, p73 was found to be a target of the enzymatic
      activity of c-Abl, a non-receptor tyrosine kinase that potently activated in
      response to DNA damage. Here, we present evidence that c-Abl induces the
      phosphorylation of p73 in threonine residues adjacent to prolines, and that the
      p38 MAP kinase pathway mediates this response. Furthermore, we found that
      activation of p38 is sufficient to enhance the stability of p73, and that the
      transcriptional activation of p73 by c-Abl requires the activity of p38. These
      findings indicate that members of the MAP kinases superfamily of signaling
      molecules can regulate p73, and support a role for the p38 MAP kinase in a novel
      biochemical pathway by which c-Abl regulates this p53-related molecule.

PMID- 11840345
TI  - Upregulation of DAF (CD55) on orbital fibroblasts by cytokines. Differential
      effects of TNF-beta and TNF-alpha.
AB  - PURPOSE: Decay accelerating factor (DAF) and membrane cofactor protein (MCP) are
      membrane complement regulators that protect self cells from deposition of
      autologous C3b on their surfaces. CD59, a third downstream regulator of the
      cascade, prevents the assembly on self cells of autologous membrane-attack
      complexes. All three proteins are highly expressed on corneal and conjunctival
      epithelia, and are present in lower levels on multiple intraocular and adnexal
      cell types. The purpose of this study was to determine whether, and if so, how
      DAF, MCP and CD59 expression by ocular and adnexyl cells is modulated by
      cytokines. METHODS: Primary cultures of orbital fibroblasts and corneal
      epithelial cells were incubated with TNF-alpha, TNF-beta, TGF-beta1, IFN-gamma,
      MIF or blocking anti-MIF mABs and extracts of the cells quantitated for DAF, MCP
      and CD59 by two-site immunoradiometric assays. Where inductions occurred, the
      kinetics of the increases, the effect of combining cytokines, and the effect of
      protein kinase-C inhibition were studied. RESULTS: DAF expression on orbital
      fibroblasts was upregulated 6.3-, 3.7- and 4.2-fold by TGF-beta1, TNF-beta and
      IFN-gamma, respectively, but that its expression on corneal epithelial cells was
      minimally affected. These same (or other) cytokines did not significantly
      upregulate MCP or CD59. The cytokine-induced upregulation of DAF expression on
      orbital fibroblasts requires 24 hr for IFN-gamma or 48 hr for TGF-beta1 or TNF
      beta, is dependent on new protein synthesis, and does not involve protein kinase
      C activation. CONCLUSIONS: TGF-beta1-, TNF-beta- and IFN-gamma-mediated
      upregulation of DAF should serve to prevent complement-mediated injury to orbital
      fibroblasts in the course of ocular inflammation. The induction by TNF-beta
      rather than TNF-alpha contrasts with that on all other cell types studied.

PMID- 11840346
TI  - Platelet-derived growth factor-BB: a survival factor for the retinal
      microvasculature during periods of metabolic compromise.
AB  - PURPOSE: The aim of this study was to test the hypothesis that platelet-derived
      growth factor (PDGF) reduces ischemia-induced damage to cells in the retinal
      microvasculature. METHODS: As a model of ischemia, pericyte-containing
      microvessels freshly isolated from the adult rat retina were exposed to the
      inhibitors of ATP synthesis, iodoacetate and antimycin A. Cell viability was
      assayed by trypan blue exclusion. RESULTS: PDGF-BB significantly reduced cell
      death induced by chemical ischemia. The half-maximally effective concentration
      was approximately 15 pM. In contrast to PDGF-BB, which is the specific ligand for
      PDGF-beta receptors, ischemic death was not reduced by PDGF-AA, which does not
      activate the beta-receptors. The protective effect of PDGF-BB was blocked by
      tolbutamide, which is an inhibitor of ATP-sensitive potassium (K(ATP)) channels
      and mimicked by the K(ATP) channel opener, pinacidil. Nifedipine, which blocks
      voltage-gated calcium channels (VGCC's), also mimicked the protective effect of
      PDGF-BB. Consistent with PDGF-BB and nifedipine preventing cell death via a
      common mechanism, i.e., reducing VGCC activity, the maximal effects of this
      growth factor and the calcium channel blocker were not additive. CONCLUSIONS: Our
      results indicate that PDGF-BB significantly reduces the vulnerability of retinal
      microvessels to damage caused by profound ischemia. During episodes of metabolic
      compromise, it appears likely that the opening of K(ATP) channels via activation
      of PDGF-beta receptors initiates an adaptive mechanism to enhance the survival of
      the retinal microvasculature.

PMID- 11840347
TI  - Immunosuppression by IL-10-transfected human retinal pigment epithelial cells in
      vitro.
AB  - PURPOSE: Retinal pigment epithelium (RPE) transplantation seems to be a possible
      therapy for restoring vision in the case of retinal degeneration. As there is a
      risk of allergic rejection, a gene-transfer of immunosuppressive cytokines into
      the graft may diminish this reaction. Therefore, we investigated the transfer of
      interleukin-10 (IL-10) into an immortalised human RPE cell line (hTERT-RPE1) and
      its effect on the proliferation of allogeneic immune competent cells. METHODS:
      The hTERT-RPE1 cells were transiently transfected with the cDNA of human IL-10
      using a lipid-based transfection reagent. The expression of IL-10 mRNA was ana
      lysed by reverse transcription-polymerase chain reaction and an enzyme-linked
      immunosorbent assay measured the secretion of the cytokine over 7 days. The
      effect of the secreted IL-10 on the proliferation of allogeneic T cells with and
      without homologous macrophages was investigated colorimetrically. To enhance this
      reaction, RPE cells were pre-activated with interferon-gamma (IFN-gamma). Anti-IL
      10 antibodies were used in a neutralising assay. RESULTS: A transfection
      efficiency of 23.3 +/- 9.03% was achieved. IL-10 mRNA could only be shown in IL
      10-transfected hTERT-RPE1 cells. The same was found for the level of cytokine,
      with a maximum on day 3 (10.34 +/- 0.09 ng/ml). A significant suppressive effect
      of the secreted IL-10 on T-cell proliferation was detectable on days 5 and 6.
      This effect could be significantly abolished with anti-IL-10 antibodies.
      CONCLUSIONS: The IL-10-producing hTERT-RPE1 cells had an immunosuppressive action
      on T-cell proliferation in vitro. A gene-transfer into RPE allografts before
      transplantation may be able to promote graft survival.

PMID- 11840348
TI  - High concentrations of glucose induce synthesis of argpyrimidine in retinal
      endothelial cells.
AB  - PURPOSE: To determine if high concentrations of glucose applied to cultured
      bovine retinal endothelial cells (BRE cells) would result in production of
      intracellular methylglyoxal (MG), and consequently, the synthesis of MG-derived
      advanced glycation end products (AGEs). METHODS: BRE cells were incubated with 30
      mM D-glucose or 30 mM L-glucose for 7 days. Cells incubated with medium that had
      5-mM glucose served as controls. Cells were lysed and the lysate was centrifuged
      to get a supernatant and a pellet fraction. We measured argpyrimidine, a MG
      derived fluorescent AGE in the two fractions by a competitive ELISA using a
      monoclonal antibody. RESULTS: BRE cells incubated with 30 mM D-glucose produced
      significantly higher (P < 0.05) levels of intracellular MG than control cells or
      cells incubated with 30 mM L-glucose. Incubation with 30 mM D-glucose
      significantly (P < 0.05) enhanced the synthesis of argpyrimidine in both
      supernatant and pellet fractions when compared to control cells.
      Immunofluorescence studies confirmed results obtained by ELISA and showed higher
      levels of argpyrimidine in cells incubated with 30 mM D-glucose. CONCLUSION:
      These results suggest that MG-mediated protein modification can occur in elevated
      glucose, and might contribute to endothelial cell changes associated with
      diabetic retinopathy.

PMID- 11840349
TI  - Proliferation in the posterior region of the lens of c-maf-/- mice.
AB  - PURPOSE: To examine the involvement of the c-maf gene in the proliferation of the
      lens cells. METHODS: Eyes of the E13 and E18 stages of the wild-type and c-maf-/-
      mice were analyzed by BrdU incorporation assay, TUNEL assay and
      immunocytochemistry using a anti-P27(KIP1) and a anti-P57(KIP2) antibody.
      RESULTS: In the E13 and E18 c-maf mutant lens, BrdU-positive cells were detected
      at the posterior region of the lens. Cell-cycle inhibitor P27(KIP1) and P57(KIP2)
      were expressed in the equatorial and posterior region of the lens of both wild
      type and c-maf-/- lenses. CONCLUSION: These results suggest that the expression
      of c-maf is required for differentiation and cell cycle arrest of lens fiber
      cells. It is also suggested that P27(KIP1) and P57(KIP2) were not involved in the
      continued proliferation of posterior region of the c-maf-/- lens.

PMID- 11840350
TI  - Effects of serotonergic compounds on aqueous humor dynamics in monkeys.
AB  - PURPOSE: The effects of several serotonergic agonists on aqueous humor formation
      (AHF), total outflow facility (OF) and intraocular pressure (IOP) were
      investigated in living cynomolgus monkeys. METHODS: We determined the effect of a
      single topical unilateral 300 microg or 3 mg dose of the 5-HT agonists serotonin,
      5-carboxamidotryptamine (5-CT), sumatripan, gepirone, and 8-hydroxy-2(di-n
      propylaminotetralin) (8-OH-DPAT) and a 450 microg dose of flesinoxan on IOP
      (Goldmann applanation tonometry), AHF (scanning ocular fluorophotometry) and
      total OF (8-OH-DPAT only, topically and intracamerally). RESULTS: Serotonin, 5
      CT, sumatripan or gepirone had no significant effect on IOP or AHF. 8-OH-DPAT
      caused an AHF increase of approximately 70% over 6 hr in both ipsilateral drug-
      and contralateral vehicle-treated eyes, but no significant change in IOP compared
      with baseline measured on a separate occasion in the same animals. 8-OH-DPAT did
      not increase protein levels or rate of entry of systemically administered
      fluorescein in the anterior chamber aqueous humor compared to historic controls,
      and no difference was seen between ipsilateral and contralateral eyes. Flesinoxan
      had no effect on IOP and produced an insignificant 25% increase in flow in
      treated eyes compared to baseline. CONCLUSION: The results for 8-OH-DPAT and
      possibly flexinoxan indicate the presence of a secretion-stimulating 5-HT1A
      receptor in monkey ciliary epithelium that has little effect on IOP. OF was
      unchanged following 8-OH-DPAT administered topically or following intracameral
      exchange.

PMID- 11840351
TI  - The effect of nipradilol, an alpha-beta blocker, on retinal blood flow in healthy
      volunteers.
AB  - PURPOSE: To study the effects of topically applied nipradilol, an alpha-beta
      blocker recently developed in Japan as an ocular hypotensive drug, on retinal
      blood flow (RBF) in healthy volunteers. METHODS: Seven healthy volunteers (mean
      age, 33 years) underwent measurement of RBF using a newly developed stabilized
      laser Doppler velocimetry system. In a double-blind trial, retinal arterial blood
      flow, intraocular pressure (IOP), and blood pressure (BP) were measured before
      and after the instillation of nipradilol or saline every hour for 5 hours.
      RESULTS: Retinal arterial blood flow and the diameter of the retinal artery
      significantly (p< 0.05) increased at 4 hours after instillation in nipradilol
      treated eyes. Retinal blood velocity did not change significantly. Nipradilol
      evoked a significant (p< 0.05) bilateral decrease in IOP. Mean BP decreased
      significantly (p< 0.05) 3 hours after instillation. Ocular perfusion pressure
      (OPP), calculated from the mean BP and IOP, did not change significantly during
      the study. CONCLUSION: Topical nipradilol significantly increased retinal
      arterial blood flow in healthy volunteers, not through a secondary effect
      dependent on a change in OPP, but likely through the vasodilatory action of the
      drug.

PMID- 11840352
TI  - The effect of topical CS-088, an angiotensin AT1 receptor antagonist, on
      intraocular pressure and aqueous humor dynamics in rabbits.
AB  - PURPOSE: To evaluate the ocular hypotensive effect of topical CS-088, an
      angiotensin AT1 receptor antagonist, and the effect of CS-088 on aqueous humor
      dynamics. METHODS: The effects of CS-088 on intraocular pressure (IOP) were
      studied in 2 models of rabbit ocular hypertension. Experimental ocular
      hypertension was induced in albino rabbits by injecting alpha-chymotrypsin into
      the anterior chamber (alpha-chymotrypsin rabbit). The effects of the single
      application of CS-088 were examined. Additionally, CS-088 was repeatedly
      administered over a period of 3 weeks to hereditary ocular hypertensive rabbits
      (buphthalmic rabbits, JWHR bu/bu) and the IOPs were monitored throughout the
      experiment. The effects of CS-088 on aqueous humor dynamics were also examined in
      normal rabbits. In this study, the methods of IOP recovery rate, two-level
      constant pressure perfusion and fluorescein-dextran perfusion were used
      respectively to determine the aqueous inflow, outflow facility and uveoscleral
      outflow (USF). RESULTS: CS-088 at 1% and 2% significantly lowered the IOP in the
      alpha-chymotrypsin rabbits with a maximum IOP reduction of 10.1 mmHg. The maximum
      effect obtained with 2% CS-088 was no greater than that with 1% CS-088. In the
      buphthalmic rabbits, 2% CS-088 also lowered IOP significantly. Timolol was
      effective in both models. In the study on aqueous humor dynamics, a slight
      increase in USF (17%) was seen after a topical application of CS-088 whereas
      changes in aqueous inflow or outflow facility were not observed. CONCLUSIONS:
      Topical CS-088 can decrease IOP in rabbits. Despite the USF change, the ocular
      hypotensive mechanism by CS-088 was not fully determined.

PMID- 11840353
TI  - The effect of angiotensin II on uveoscleral outflow in rabbits.
AB  - PURPOSE: In our previous study, we showed that the AT1 receptor antagonist
      increased uveoscleral outflow (USF) when topically applied to the rabbit eye.
      However this increase was too small to demonstrate a clear physiological role for
      ocular angiotensin II (AII). Hence, the purpose of this study was to determine
      whether ocular AII influenced USF regulation, and if so, how this occurred.
      METHODS: USF was measured by the FITC-dextran perfusion method in albino rabbits.
      AII and its receptor antagonists were directly applied into the anterior chamber
      by adding into the perfusate and by perfusing with FITC-dextran. We also analyzed
      angiotensin receptors on the rabbit ciliary body membrane by a receptor binding
      assay with 125I-[Sar1), Ile8]-AII as a ligand. RESULTS: CS-088 (1 microg/ml)
      increased USF by 24% while AII decreased USF in a concentration-dependent manner
      between 10 and 500 nM. Its maximum decrease of 19% occurred at 500 nM. At this
      AII concentration the USF reduction was antagonized by 1 microg/ml CS-088, an AT1
      receptor antagonist, but not by the same concentration of PD-123,177, an AT2
      receptor antagonist. Specific 125I-[Sar1, Ile8]-AII binding to the rabbit ciliary
      body membranes was inhibited by CS-088 with an inhibition constant of 7.05 nM,
      whereas inhibition by PD-123,177 was not observed. CONCLUSIONS: Ocular AII was
      indicated to attenuate USF via AT1 receptors in rabbits, however its
      physiological effect was not critical in IOP regulation.

PMID- 11840355
TI  - Recognizing periodic alternating nystagmus.
AB  - Congenital or acquired periodic alternating nystagmus (PAN) is characterized by
      nystagmus occurring in a cycle. The cycle consists of a left-beating nystagmus, a
      transition phase, a right-beating nystagmus, and a further transition phase. The
      purpose of this review is to assist the clinician in the recognition of periodic
      alternating nystagmus (PAN), either as a type of congenital nystagmus or in its
      acquired form, and to highlight why such identification is important. Recent
      studies using eye movement recordings are reviewed to point out the frequency of
      congenital PAN in samples of patients with congenital nystagmus, and to describe
      the characteristics of the waveforms and the influence of foveation time on the
      alternation of head turns. Classical and new surgical alternatives are reported.
      The identification of congenital PAN is essential when surgical treatment is
      being considered for the correction of anomalous head postures. Acquired PAN is
      usually due to cerebellar disease and causes oscillopsia. Unlike other forms of
      acquired nystagmus, it responds well to drug treatment.

PMID- 11840354
TI  - Flesinoxan, a 5-HT1A receptor agonist/alpha 1-adrenoceptor antagonist, lowers
      intraocular pressure in NZW rabbits.
AB  - PURPOSE: alpha1-Adrenoceptor antagonists and 5-HT1A receptor agonists reduce
      intraocular pressure (IOP) in the rabbit. The aims of this study were firstly, to
      determine the IOP-lowering effects of flesinoxan and selected other hybrid 5-HT1A
      receptor agonists/alpha1-adrenoceptor antagonists, and secondly, to investigate
      the mechanism of action of the IOP response to flesinoxan. METHODS: IOP and total
      outflow facility were measured in rabbits after administration of hybrid drugs.
      Inositol phosphates accumulation assays were performed using standard
      methodologies. RESULTS: Topical unilateral instillation of the drugs caused dose
      related reductions of IOP. Comparison of the compounds tested revealed a potency
      order of WB 4101 > flesinoxan > 5-methyl-urapidil > or = BMY7378 > urapidil. WB
      4101 caused a small increase in total outflow facility whereas flesinoxan had no
      effect. Measurement of the IC50 values for inhibition of phenylephrine-stimulated
      inositol phosphates accumulation in rabbit iris-ciliary body revealed a potency
      order of WB 4101 > 5-methyl-urapidil > flesinoxan > BMY 7378 = urapidil. Topical
      flesinoxan was ineffective in reversing phenylephrine-induced mydriasis, yet,
      pretreatment with the 5-HT1A receptor antagonists MDL 73005EF and pindolol only
      partially blocked the hypotensive effect of topical flesinoxan. CONCLUSIONS: The
      present studies indicate the potent and efficacious IOP-lowering capabilities of
      flesinoxan and certain other ligands with affinity for 5-HT1A receptors/alpha1
      adrenoceptors. The exact mechanisms by which these drugs lower IOP in the rabbit
      are complex but our results indicate that flesinoxan likely reduces aqueous
      secretion.

PMID- 11840356
TI  - Squint surgery in the over sixties.
AB  - We examined the indications for strabismus surgery in patients 60 years of age or
      older. A retrospective review was carried out of 111 case records of such
      patients operated on between January 1992 and May 1999. There were 59 females and
      52 males, ranging in from 60 to 90 years (mean 67.3 years). The diagnoses were
      varied: the largest groups were cranial nerve palsies and consecutive strabismus.
      Fifty-six patients demonstrated binocular potential pre-operatively and 60 post
      operatively. Twenty-three patients underwent reoperation. Twenty-eight patients
      also received botulinum toxin. The mean follow-up was 15 months, 54 patients were
      discharged within 6 months. Elective strabismus surgery in this age group
      constituted 7% of strabismus surgery activity (single surgeon). There were no
      complications. There is a demand for strabismus surgery in this ever increasing
      age group.

PMID- 11840357
TI  - Adjustable squint surgery in children.
AB  - The adjustable suture technique in adult strabismus surgery is well established.
      The aim of this study was to assess its feasibilty/outcome in a younger age
      group. A retrospective review of 359 case notes of patients, under the age of 16
      years, who underwent squint surgery between 1992 and 1999 was carried out. Of
      these, 45 (13%) had undergone surgery with the adjustable suture technique. Post
      operatively, 34 patients achieved an angle of +/- 10 pd and required no further
      treatment. We sought co-operation from the parents and encouraged their active
      participation during adjustment. It was not necessary for any child to return to
      the operating theatre to finalise adjustment. We conclude that this is an
      effective treatment in motivated children, as 76% (34/45) obtained an excellent
      result.

PMID- 11840358
TI  - Bilateral recession-resection surgery for convergent strabismus fixus associated
      with high myopia.
AB  - The authors report two patients with more than 20 diopters of myopia, severely
      restricted abduction, and more than 90Delta of acquired esotropia. Marked axial
      elongation of the globes was present. Each underwent large bilateral medial
      rectus recessions and bilateral lateral rectus resections. The deviations were
      significantly reduced and abduction improved with combined horizontal recession
      resection surgery on both eyes.

PMID- 11840359
TI  - Abduction paralysis with hypotropia: sign of weakness of a contralateral superior
      oblique.
AB  - background The clinical diagnosis of extraocular motor paralysis that is caused
      by severe cranial trauma can often be complicated. The resulting clinical picture
      can make the identification of all the components of potentially treatable
      oculomotor problems difficult. methods We examined five cases of complete
      abducens nerve paralysis with marked downshoot in attempted abduction seen after
      severe cranial trauma. results With the patients looking in the field of gaze of
      the paralysis, a marked infraductive movement of the paralytic eye occurred while
      the other eye maintained fixation. Other clinical findings confirmed this to be a
      secondary deviation due to a paresis of the contralateral superior oblique.
      conclusion Patients with a paralysis of the lateral rectus following a severe
      cranial trauma who demonstrate a marked downshoot of the involved eye should be
      suspected of having a paresis of the contralateral superior oblique. This
      diagnosis has helped us effectively to treat this vertical incomitance by a
      simple weakening procedure of the contralateral inferior oblique.

PMID- 11840360
TI  - Genomewide scan of hoarding in sib pairs in which both sibs have Gilles de la
      Tourette syndrome.
AB  - A genome scan of the hoarding phenotype (a component of obsessive-compulsive
      disorder) was conducted on 77 sib pairs collected by the Tourette Syndrome
      Association International Consortium for Genetics (TSAICG). All sib pairs were
      concordant for a diagnosis of Gilles de la Tourette syndrome (GTS). However, the
      analyses reported here were conducted for hoarding as both a dichotomous trait
      and a quantitative trait. Not all sib pairs in the sample were concordant for
      hoarding. Standard linkage analyses were performed using GENEHUNTER and Haseman
      Elston methods. In addition, novel analyses with a recursive-partitioning
      technique were employed. Significant allele sharing was observed for both the
      dichotomous and the quantitative hoarding phenotypes for markers at 4q34-35
      (P=.0007), by use of GENEHUNTER, and at 5q35.2-35.3 (P=.000002) and 17q25
      (P=.00002), by use of the revisited Haseman-Elston method. The 4q site is in
      proximity to D4S1625, which was identified by the TSAICG as a region linked to
      the GTS phenotype. The recursive-partitioning technique examined multiple markers
      simultaneously. Results suggest joint effects of specific loci on 5q and 4q, with
      an overall P value of.000003. Although P values were not adjusted for multiple
      comparison, nearly all were much smaller than the customary significance level
      of.0001 for genomewide scans.

PMID- 11840363
TI  - Hemodialysis-associated hypertension: pathophysiology and therapy.
AB  - The majority of end-stage renal disease (ESRD) patients are hypertensive.
      Hypertension in the hemodialysis patient population is multifactorial. Further,
      hypertension is associated with an increased risk for left ventricular
      hypertrophy, coronary artery disease, congestive heart failure, cerebrovascular
      complications, and mortality. Antihypertensive medications alone do not
      adequately control blood pressure (BP) in hemodialysis patients. There are,
      however, several therapeutic options available to normalize BP in these patients,
      often without the need for additional drug therapy (eg, long, slow hemodialysis;
      short, daily hemodialysis; nocturnal hemodialysis; or, most effectively, dietary
      salt and fluid restriction in combination with reduction of dialysate sodium
      concentration). Optimal BP in dialysis patients is not different from
      recommendations for the general population, even though definite evidence is not
      yet available. Predialysis systolic and diastolic BPs are of particular
      importance. Left ventricular mass correlates with predialysis systolic BP.
      Survival is better in hemodialysis patients with a mean arterial pressure below
      99 mm Hg as compared with those with higher BP. Low predialysis systolic BP (<110
      mm Hg) and low predialysis diastolic BP (<70 mm Hg) are associated with increased
      mortality, primarily because of severe congestive heart failure or coronary
      artery disease. Patients that experience repeated intradialytic hypotensive
      episodes should also be viewed with caution, and predialytic BP values should be
      reevaluated. A possible treatment option for these patients may be slow, long
      hemodialysis; short, daily hemodialysis; or nocturnal hemodialysis. Among the
      antihypertensive agents currently available, angiotensin-converting enzyme (ACE)
      inhibitors appear to have the greatest ability to reduce left ventricular mass.
      Pressure load can be satisfactorily determined by using the average value of
      predialysis BP measurements over 1 month. In selected hemodialysis patients,
      interdialytic ambulatory blood pressure monitoring (ABPM) may help to determine
      if the patient is in fact hypertensive. In addition, ABPM provides important
      information about the change in BP between day and night. Regular home BP
      monitoring, yearly echocardiography, and treatment of traditional risk factors
      for cardiovascular disease are recommended.

PMID- 11840364
TI  - Nutritional status in the HEMO Study cohort at baseline. Hemodialysis.
AB  - The nutritional status of the first 1,000 patients randomized into the
      Hemodialysis (HEMO) Study was analyzed at baseline when they received their
      typical dialysis dose (equilibrated Kt/V = 1.30 +/- 0.22) and dialysis membrane.
      This is the largest study to date of the nutritional status of chronic
      hemodialysis patients. The mean (+/- SD) values for these parameters included a
      serum albumin level of 3.65 +/- 0.38 g/dL, a dietary energy intake of 22.9 +/-
      8.4 kcal/kg/day, a dietary protein intake of 0.93 +/- 0.36 g/kg/day, and a double
      pool normalized protein catabolic rate (enPCR) of 1.00 +/- 0.25 g/kg/day. The
      percentage of patients below HEMO Study nutritional standards of care included
      29% of patients with a serum albumin level less than 3.5 g/dL, 76% of patients
      with a dietary energy intake less than 28 kcal/kg/day, 61% of patients with a
      dietary protein intake less than 1.0 g/kg/day, and 52% of patients with an enPCR
      of less than 1.0 g/kg/day. There was a strong correlation between dietary protein
      intake and dietary energy intake (r = 0.74, P < 0.0001). Significant correlations
      were also evident between serum albumin and double pool PCR and between dietary
      protein intake and double-pool PCR. Kt/V and membrane flux were not predictive of
      baseline dietary protein intake, dietary energy intake, or serum albumin level.
      Thus, a majority of patients in the HEMO Study had protein and energy intake
      levels and enPCR levels that were below National Kidney Foundation Kidney
      Dialysis Outcome Quality Improvement (NKF-K/DOQI) guidelines.

PMID- 11840365
TI  - Effects of exercise training plus normalization of hematocrit on exercise
      capacity and health-related quality of life.
AB  - The limitation to exercise capacity in hemodialysis patients has been attributed
      to anemia. We report the effects of normalization of hematocrit levels by using r
      hu-recombinant erythropoietin and exercise training on exercise capacity and self
      reported physical functioning in hemodialysis patients. Sixty-five patients were
      randomized into 1 of 4 groups: usual hematocrit (30%-33%) with no exercise
      training (UH); usual hematocrit (30%-33%) plus exercise training (UHX);
      normalized hematocrit (40%-42%) with no exercise training (NH); and normalized
      hematocrit (40%-42%) plus exercise training (NHX). Treadmill exercise testing was
      conducted at baseline and at 5 months after the initiation of the interventions.
      Analysis was performed on the data collapsed for 48 patients who met the criteria
      for hematocrit and exercise adherence and completed both baseline and post
      intervention (5.6 +/- 1.6 months) testing. Significant effects of exercise were
      found in peak oxygen uptake measurements (P = 0.03) and in self-reported physical
      functioning as measured by the Short Form-36 questionnaire (P = 0.01). There was
      a significant effect of hematocrit on the General Health scale on the SF-36 (P =
      0.03). The changes in peak oxygen uptake with exercise training were small and
      levels remained lower than age-predicted values at the end of the study. These
      results indicate that there are other physiologic limitations to exercise
      capacity that are not overcome by exercise training or normalization of
      hematocrit. The effects of exercise training on self-reported physical
      functioning may be of clinical importance because these scores have been shown to
      be highly predictive of outcomes such as hospitalizations and mortality in
      hemodialysis patients.

PMID- 11840366
TI  - Changes of serum albumin and C-reactive protein are related to changes of
      interleukin-6 release by peripheral blood mononuclear cells in hemodialysis
      patients treated with different membranes.
AB  - Protein malnutrition, a condition associated with an albumin concentration less
      than 3.5 g/dL, has been shown to be a major risk factor for increased mortality
      in hemodialysis patients. The aim of this cross-over study was to evaluate the
      relationship between the type of membrane adopted and serum albumin changes by
      measuring peripheral blood mononuclear cells (PBMC) interleukin-6 (IL-6) release,
      serum albumin, and plasma concentrations of C-reactive protein (CRP) in 18
      patients dialyzed with different membranes. During the study, all patients were
      dialyzed with cuprophan (CU), synthetically modified cellulosic (SMC) membrane (a
      new cellulosic membrane with lesser complement activation), and cellulose
      diacetate (CD) membrane, and have served as their own controls. IL-6 spontaneous
      release by PBMC resulted after 3 months of SMC (436.2 +/- 47.4 pg/mL)
      significantly (P < 0.05) reduced as compared with CU (569.3 +/- 24.5 pg/mL). This
      effect was more evident after 6 months of dialysis with SMC (220 +/- 35.3 pg/mL,
      P < 0.01 versus CU and versus 3 months of SMC). The passage to CD membrane was
      followed by a progressive new increase in the IL-6 PBMC release (332.3 +/- 30.7
      after 3 months, and 351.2 +/- 35.8 pg/mL after 6 months, respectively) that,
      however, remained significantly (P < 0.05) lower than CU. The behavior of CRP
      plasma levels resembled that of IL-6 PBMC release (23.3 +/- 4.7 in CU, 11.0 +/-
      2.1 after 3 months in SMC, and 7.9 +/- 1.5 after 6 months in SMC, respectively).
      IL-6 release values were positively correlated with circulating levels of CRP (r
      = 0.3264, P < 0.002). Serum albumin increased after 6 months of dialysis with SMC
      membranes (3.25 +/- 0.09 g/dL in CU and 3.64 +/- 0.07 g/dL in SMC, P < 0.05).
      When the patients were switched to CD, serum albumin showed a slight, though not
      statistically significant, decrease. Serum albumin concentrations negatively
      correlated with both IL-6 release values (r = -0.247, P < 0.05) and CRP plasma
      levels (r = -0.433, P < 0.001). In conclusion, our data clearly show that a
      significant relationship exists between biocompatibility of the membranes and
      serum albumin changes; serum albumin levels, in fact, are negatively correlated
      with the PBMC spontaneous IL-6 release values and CRP circulating levels.

PMID- 11840367
TI  - Elevated interleukin-6 predicts progressive carotid artery atherosclerosis in
      dialysis patients: association with Chlamydia pneumoniae seropositivity.
AB  - The cardiovascular mortality rate is unacceptably high in patients with end-stage
      renal disease (ESRD), which suggests an accelerated atherogenic process. The
      cause(s) of the accelerated atherogenesis in ESRD patients are not known, though
      recent studies suggest that persistent infection, such as Chlamydia pneumoniae,
      and proinflammatory cytokines may contribute. Forty-five ESRD patients (26 men)
      aged 51 +/- 2 years was studied at a time-point close to start of dialysis
      treatment and again after about 12 months of dialysis treatment. By using
      noninvasive B-mode ultrasonography, we evaluated changes in a surrogate marker of
      atherosclerosis, calculated intima media (cIM) area, in the common carotid
      artery. C-reactive protein (CRP), S-albumin, and interleukin-6 (IL-6) assessed
      the presence of an inflammatory reaction. We also measured C pneumoniae
      antibodies by microimmunofluorescence, nutritional status by subjective global
      assessment, lipid parameters, smoking habits, and the presence of comorbidity
      close to the start of dialysis. No significant changes in the prevalence of
      carotid plaques or the mean cIM area were observed during the first 12 months of
      dialysis. However, because some patients showed marked increases in the cIM area
      during only 12 months of dialysis we divided the patients into 2 groups: 23
      nonprogressors ((delta)cIM area -2.7 +/- 0.4 mm2) and 22 progressors ((delta)cIM
      area 3.6 +/- 0.7 mm2). Sex, age, body mass index, comorbidity, blood lipid
      levels, S-albumin, and CRP levels did not differ significantly between the 2
      groups. On the other hand, progressors had a significantly elevated basal median
      level of IL-6 (5.7 versus 3.1 pg/mL; P < 0.05) and an increased prevalence of
      positive (> or 1/64) immunoglobulin (Ig) A antichlamydia antibodies (59% versus
      17%; P < 0.01) compared with nonprogressors. A significant positive (R = 0.41; P
      < 0.01) correlation was found between Log IL-6 and changes in the cIM area during
      12 months of dialysis. In a stepwise multiple regression model, Log IL-6 did
      predict, independently (P < 0.01) of traditional risk factors and C pneumoniae
      antibodies, changes in the cIM area. These data suggest that a persistent
      chlamydial infection stimulates IL-6 levels, which in turn may be involved in the
      pathogenesis of accelerated carotid atherosclerosis in dialysis patients.

PMID- 11840368
TI  - Safety and efficacy of simvastatin in hypercholesterolemic patients undergoing
      chronic renal dialysis.
AB  - Dyslipidemia is universal but hypercholesterolemia per se is present in around
      50% of dialysis patients. Although dietary therapy is of benefit in some, the
      majority require drug therapy. We compared the efficacy and safety of simvastatin
      plus an optimized lipid-lowering dialysis diet with placebo plus diet in a
      randomized, double-blind trial stratified for dialysis modality. Patients treated
      with hemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD) for at
      least 9 months and with serum non-high-density lipoprotein (HDL) cholesterol
      greater than 135 mg/dL, low-density lipoprotein (LDL) greater than 116 mg/dL, and
      triglyceride less than 600 mg/dL after a 6-week dietary treatment phase and an 8
      week diet plus placebo run-in phase, were enrolled in the 24-week double-blind
      treatment phase. Fifty-seven patients (16 men, 41 women, median age 63 years,
      range 22-75 yr) were randomized 2:1 to diet plus 5 mg/day simvastatin (n = 38: 22
      HD, 16 CAPD) or diet plus placebo (n = 19: 12 HD, 7 CAPD) for 24 weeks. Dose was
      doubled bimonthly (maximum 20 mg/day) if non-HDL cholesterol was greater than 135
      mg/dL. Forty-two patients (73.7%) completed the trial. Comparing baseline and 24
      weeks, simvastatin (median 10 mg/day) was significantly more effective than
      placebo in reducing serum non-HDL cholesterol concentrations. For HD, the median
      percentage changes for total cholesterol (TC) (simvastatin versus placebo) were 
      21.4% and -12.1% (P = 0.011), respectively; for LDL cholesterol, -33.0% and -8.8%
      (P = 0.023); for non-HDL cholesterol, -25.2% and -14.0% (P = 0.008); and for
      TC:HDL, -17.65% and -1.67% (P = 0.008). For CAPD, changes for TC were -22.1% and 
      1.5% (P = 0.003), respectively; for LDL, -36.4% and 0.0% (P = 0.001); for non-HDL
      cholesterol, -24.9% and -3.6% (P = 0.002); and for TC:HDL ratio, -21.49% and
      +9.74% (P = 0.045). Changes with CAPD in apolipoprotein (Apo) A1 were -4.7% and
      +4.0% (P = 0.031); and for ApoB, -19.9% and +2.6%, respectively (P = 0.031).
      There were no significant changes in ApoA1 or ApoB with HD. Compared with
      placebo, triglyceride levels fell 10.2% with HD and 6.2% with CAPD. HDL
      cholesterol was unchanged with HD but rose 8.5% with CAPD. These trends, however,
      did not reach statistical significance (P > 0.05). There was no effect on Lp (a).
      The incidence of clinical and laboratory adverse experiences were not increased
      in the simvastatin-treated patients compared with placebo. Simvastatin appears to
      be a safe and effective treatment for the reduction of serum non-HDL cholesterol
      levels in both HD and, particularly, CAPD patients.

PMID- 11840369
TI  - Conjunctival and corneal calcification and bone metabolism in hemodialysis
      patients.
AB  - Conjunctival and corneal calcification is well recognized as a metastatic
      calcification in patients undergoing hemodialysis. In 44 male hemodialysis
      patients, we examined the relationship between the severity of conjunctival and
      corneal calcification and age; duration of hemodialysis; serum levels of calcium
      (Ca), phosphorus (P), intact parathyroid hormone (iPTH), alkaline phosphatase
      (ALP), and osteocalcin; and bone mineral density (BMD). The mean age was 58.3
      years (range, 33-79 yr), and the mean duration of hemodialysis was 94.3 months
      (range, 25-258 mo). The serum level of Ca was 9.6 +/- 0.1 mg/dL, P was 5.9 +/-
      0.1 mg/dL, Ca x P was 57.5 +/- 1.2, iPTH was 204.0 +/- 34.6 pg/mL, ALP was 173.8
      +/- 11.8 U/L, and osteocalcin was 62.8 +/- 9.5 ng/mL. Lumbar BMD was 0.997 +/-
      0.022 g/cm2 and radial BMD was 0.642 +/- 0.015 g/cm2. There was a significant
      positive correlation between the severity of conjunctival and corneal
      calcification and the duration of hemodialysis (P < 0.0001), the serum levels of
      P (P = 0.0035), the Ca x P (P = 0.0034), the iPTH (P = 0.0154), the ALP (P <
      0.0001), and the osteocalcin (P = 0.0010), and was negatively correlated with
      radial BMD (P = 0.0008). However, the severity of conjunctival and corneal
      calcification was not significantly correlated with age (P = 0.986), serum Ca
      levels (P = 0.138), or lumbar BMD (P = 0.449). Based on these findings, we
      suggest that the conjunctival and corneal calcification developed by excessive
      serum levels of Ca and P associated with abnormal bone and mineral metabolism.
      This resulted in an increased bone turnover and decreased BDM after prolonged
      hemodialysis even though efforts were made to maintain the homeostasis of Ca and
      P metabolism in hemodialysis patients by using various therapeutic approaches.

PMID- 11840370
TI  - Long-term glycemic control measurements in diabetic patients receiving
      hemodialysis.
AB  - Cardiovascular morbidity is increased in patients with diabetes mellitus and
      there is a great prevalence of diabetes and cardiovascular disease among patients
      with end-stage renal disease (ESRD). Control of glycemia can decrease
      cardiovascular and end-organ damage. Because the validity of glycemic control
      tests have not been rigorously studied in patients with ESRD, we evaluated the
      value of various measures in these patients. The overall clinical goal was to
      investigate whether hemoglobin A1C (A1C) accurately reflects actual glycemic
      control as compared with other measures in light of the importance of attaining
      appropriately controlled blood glucose (BG). The commonly used tests of total
      glycated hemoglobin (GHb) and A1C may be unreliable in patients with ESRD because
      of the presence of anemia, shortened red blood cell (RBC) survival, and assay
      interferences from uremia. The primary aim of this study was to assess the
      relationship of capillary BG measurements to A1C, GHb, total glycated plasma
      proteins (GPP), and fructosamine (Fr) in diabetic patients receiving
      hemodialysis. Twenty-three patients were instructed to obtain BG evaluations
      twice daily for 7 days by using the Elite glucometer (Bayer Corporation, Elkhart,
      IN). These determinations included 6 fasting, 6 preprandial, and 3 separate 2
      hour postprandial levels. Blood was obtained on day 7 for measurement of A1C,
      GHb, GPP, and Fr. A1C was analyzed by an immunoassay, GPP and GHb were assayed by
      affinity high-performance liquid chromatography (HPLC), and Fr by automated
      nitroblue colorimetric assay. Scatter plots were generated by plotting the
      average BG versus A1C, GHb, GPP, or Fr. Linear regression was performed for each
      plot showing the following relationships: A1C = 0.0174 (BG) + 4.76 (r = 0.58; P <
      0.05): GHb = 0.0371 (BG) + 3.57 (r = 0.584; P < 0.05): GPP = 0.0083 (BG) + 26.13
      (r = 0.065; P = 0.77): Fr = 0.6865 (BG) + 250 (r = 0.345; P = 0.11). Despite
      anemia and shortened RBC lifespan in patients with ESRD, A1C in the range of 6%
      to 7% estimates glycemic control similarly to patients without severe renal
      impairment. A1C values above 7.5% may overestimate hyperglycemia in patients with
      ESRD. Thus, diabetic patients receiving hemodialysis may have long-term BG that
      are more properly controlled than previously determined, reducing their risks of
      the macro- and microvascular complications of diabetes mellitus.

PMID- 11840371
TI  - Predicting 30-minute postdialysis blood urea concentrations using the stop
      dialysate flow method.
AB  - The stop dialysate flow (SDF) method has been the recommended method of
      postdialysis urea sampling by the Scottish Renal Association since November 1998.
      However, this method does not lend itself to calculation of Kt/V using currently
      favored formulas, which require either a 30-minute postdialysis sample or a 20
      second "slow flow" sample. We, therefore, derived a formula that uses a 5-minute
      postdialysis urea sample using the SDF method to estimate the urea concentration
      at 30 minutes. Blood samples were obtained from 70 hemodialysis patients
      immediately before dialysis and at 0, 5, and 30 minutes postdialysis. Half of the
      patients from each unit were randomly selected to form the linear regression
      equation: Estimated 30-minute urea concentration = 1.06 x (5-minute urea
      concentration) + 0.22. This equation was validated using the data from the
      remaining 35 patients. This showed a very close correlation between measured and
      estimated urea concentration at 30 minutes (R2 = 0.97), and a Bland-Altman plot
      confirmed this close relationship. The sensitivity, specificity, positive, and
      negative predictive values of this equation were high when used to estimate 30
      minute urea reduction ratio (URR) greater than 65% (100%, 85.7%, 97%, and 100%,
      respectively) and 30-minute Kt/V greater than 1. 2 (96.7%, 100%, 100%, and 80%,
      respectively). The coupling of the SDF method with the above formula combines the
      advantages of simple and reproducible postdialysis blood sampling with an
      accurate estimation of the 30-minute postdialysis blood urea concentration, URR,
      and Kt/V. This method should be a useful tool for comparative audit of
      hemodialysis adequacy.

PMID- 11840372
TI  - Regional citrate anticoagulation for hemodialysis using a conventional calcium
      containing dialysate.
AB  - Regional citrate anticoagulation is currently a frequently applied technique for
      hemodialysis patients at increased risk of bleeding. Most experience exists with
      isotonic citrate in combination with a calcium-free dialysate and separate
      substitution with calcium chloride. This method is effective, but rather
      cumbersome and laborious. In search for a less demanding, but equally safe and
      effective technique, we performed 203 double-needle hemodialysis sessions in 45
      patients at high risk of bleeding using regional anticoagulation with hypertonic
      trisodium citrate (TSC) and a conventional calcium-containing dialysate. At the
      start of dialysis, citrate was infused at a rate of 75 mL/h; adjustments were
      made during dialysis according to the degree of anticoagulation and level of
      ionized calcium within the systemic circuit. The efficacy and short-term safety
      of regional anticoagulation with TSC as compared with heparin anticoagulation was
      ascertained in a cohort of 19 stable hemodialysis patients. Systemic
      anticoagulation did not occur, and plasma-ionized calcium remained on a stable
      level. Manifestations of citrate toxicity or hypocalcemia were not observed.
      Clotting within the dialyzer was noted in 18 of the 203 sessions (8.87%) and
      resulted in early termination of dialysis in only 3 cases (1.48%). In conclusion,
      the use of hypertonic TSC and a conventional calcium-containing dialysate was
      shown to be safe and effective. The risk of clotting of the extracorporeal
      circuit is limited and outweighed by the advantage of reduced procedural
      complexity. Compared with the use of a calcium-free dialysate, the number of
      analyses can be reduced substantially, making this method financially attractive.

PMID- 11840373
TI  - Comorbidity and other factors associated with modality selection in incident
      dialysis patients: the CHOICE Study. Choices for Healthy Outcomes in Caring for
      End-Stage Renal Disease.
AB  - Case-mix factors influence both the selection of dialysis modality and outcomes
      in end-stage renal disease (ESRD). A detailed characterization of the case-mix
      differences between peritoneal dialysis (PD) and hemodialysis (HD) patients at
      the onset of dialysis therapy has not been performed, despite the importance of
      accounting for baseline differences in future comparisons of outcomes across
      modality groups. We compared baseline characteristics of 279 PD and 759 HD
      patients enrolled in the Choices for Healthy Outcomes in Caring for End-Stage
      Renal Disease (CHOICE) Cohort Study, a prospective study of incident dialysis
      patients. Comorbidity was assessed using the Index of Coexistent Diseases (ICED),
      consisting of a medical record review of 19 medical conditions and an observer
      based assessment of 11 physical functions. ICED scores range from 0 to 3, with
      higher levels reflecting more severe comorbidity. Comorbidity was less severe in
      PD patients than in HD patients: the proportions of patients with ICED 0-1, ICED
      2, and ICED 3 were 52%, 26%, and 22%, respectively, among the PD patients and
      30%, 39%, and 31%, respectively, among the HD patients (P < 0.001). After
      controlling for all other factors, the differences in comorbidity remained
      significant. As compared with patients with ICED 0-1, the odds of being treated
      with PD for patients with ICED 2 and ICED 3 were less (odds ratio [OR] and 95%
      confidence intervals) 0.31 (0.17 to 0.56) and 0.50 (0.28 to 0.90), respectively.
      The number and severity of comorbid conditions at the onset of ESRD is
      significantly lower in patients choosing PD, independent of other factors
      influencing modality selection. The increased survival of PD patients reported in
      recent studies may simply reflect the self- or physician-directed selection of
      healthier patients to PD. Adjustment for case-mix differences in patients treated
      with PD versus HD is essential to the assessment of the independent effect of the
      dialysis modality on outcomes.

PMID- 11840374
TI  - Mupirocin resistance after long-term use for Staphylococcus aureus colonization
      in patients undergoing chronic peritoneal dialysis.
AB  - Mupirocin (Mup) has been used extensively to prevent Staphylococcus aureus (SAu)
      infections in patients undergoing peritoneal dialysis (PD). Resistance to Mup has
      been reported, but its relevance after long-term use of this drug in PD is
      unknown. Colonization by SAu was treated with topic Mup in our unit between
      September 1990 and December 2000. Sensitivity to Mup was tested in 437 strains of
      SAu isolated from 155 PD patients and 62 dialysis partners. Resistance to Mup was
      classified as low (minimal inhibitory concentration [MIC] > or = 8 microg/mL) or
      high (MIC > or = 512 microg/mL) degree. MIC90 was 0.125 microg/mL in 1990 to 1996
      (5% low, 0% high-degree resistance), 64 microg/mL in 1997 to 1998 (6.6% low, 8.3%
      high-degree resistance), and 1,024 microg/mL in 1999 to 2000 (2.3% low, 12.4%
      high-degree resistance). Mup-resistant SAu were isolated from 25 patients and 13
      partners a median of 15 months after starting PD. Resistance was associated
      frequently with repeated treatments of SAu recolonization, but was detected in 3
      cases at the start of PD therapy. The accumulated incidence of SAu exit-site
      infection in the period 1997 to 2000 was 32.3% in patients colonized by Mup
      resistant SAu as compared with 14.5% in those colonized by Mup-sensitive SAu (P =
      0.03). Mup-resistant SAu have emerged in a significant proportion of our PD
      patients and dialysis partners. This emergence has resulted in a moderate, but
      significant, increase in the risk of SAu exit-site infection and raises concerns
      about the future of Mup as the therapy of choice for SAu colonization in patients
      undergoing chronic PD.

PMID- 11840375
TI  - Persistent elevation of C-reactive protein and ischemic heart disease in patients
      with continuous ambulatory peritoneal dialysis.
AB  - We evaluated the association between a persistent elevation of C-reactive protein
      (CRP) level and the presence or severity of ischemic heart disease (IHD) in
      patients with continuous ambulatory peritoneal dialysis (CAPD). Seventy-three
      patients, who were over 40 years old, underwent dipyridamole thallium single
      photon emission computed tomography (SPECT), and followed-up for more than 1 year
      were enrolled. We measured stored plasma for CRP every 3 months. Elevation of CRP
      was defined as greater than or equal to 5 mg/L and persistent elevation of CRP as
      elevated CRP levels that lasted longer than 6 months. Serum albumin, cholesterol,
      lipoprotein(a), and plasma fibrinogen were measured at 3 months after the start
      of CAPD. Twenty-six patients showed an elevation of CRP for more than 6 months
      during the follow-up period. Twenty-eight patients showed positive findings on
      thallium SPECT. Coronary angiography showed significant stenosis (narrowing of
      the diameter more than 50%) in 23 of the 25 patients studied. Seventeen (65%) of
      26 patients who had an elevated CRP level for longer than 6 months had positive
      thallium SPECT. The presence of diabetes, albumin, fibrinogen, and the presence
      of a persistent elevation of CRP were different between the patients with
      positive (n = 28) or negative thallium SPECT (n = 45). A multivariate logistic
      regression analysis showed that a persistent elevation of CRP is the only
      predictor of positive thallium SPECT (P = 0.002). There was a tendency of
      association, although it was not statistically significant, between the
      persistence of CRP elevation and the severity of IHD (P = 0.066). Three of 9
      patients who had a persistent elevation of CRP and a negative thallium SPECT had
      a history of cerebral infarction or peripheral vascular disease. Therefore, 77%
      (20/26) of an elevated CRP level that lasted longer than 6 months can be
      explained by the presence of IHD or other atherosclerotic vascular disease. In
      conclusion, a persistent elevation of CRP level in patients with CAPD was
      strongly associated with IHD. For patients who have a persistent elevation of CRP
      without an apparent cause, we recommend a workup for IHD or other atherosclerotic
      cardiovascular disease.

PMID- 11840376
TI  - Role of macrophages and lymphocytes in the induction of neovascularization in
      renal allograft rejection.
AB  - The aim of this study was to clarify the relationship between angiogenesis and
      mononuclear cell infiltration in renal allografts. Kidney biopsies from 70 renal
      transplant recipients were evaluated. The density of CD68, CD3, and HLA-DR
      positive infiltrating cells were semiquantitatively assessed by
      immunohistochemistry. Microvessels were highlighted by immunostaining endothelial
      cells for factor VIII-RA. Of the 70 patients, 38 showed acute rejection (AR), and
      32 showed chronic rejection (CR). The mean microvessel density (MVD) in the AR
      cases was 931.6 +/- 82 and 481.6 +/- 43.6 in the CR cases. MVD in the controls
      was 210.4 +/- 21.7. A significant difference was found between the 3 groups (P <
      0.001). There were significant positive correlations between MVD and the
      proportions of the various types of mononuclear cells in the interstitial tissue
      in both the AR (P < 0.001) and CR (P < 0.001) groups. In the CR group, mean MVD
      increased in parallel with increasing interstitial fibrosis (P < 0.001). In
      follow-up biopsies, 23 of 38 patients with AR showed variable degrees of
      interstitial fibrosis. The mean MVD in the initial biopsy was 537.2 +/- 46.8 in
      cases that showed no fibrosis in follow-up biopsies, whereas mean MVD in the
      initial biopsy was 1,196 +/- 98.7 in 23 patients who showed interstitial fibrosis
      in follow-up biopsies. The difference between these values was significant (P <
      0.001). Patients with AR whose initial biopsies showed high MVD developed
      interstitial fibrosis earlier and had poorer graft outcome than those whose
      initial biopsies showed low MVD. The results suggest that advanced
      tubulointerstitial injury and mononuclear cell infiltration may play an important
      role in the induction of angiogenesis. Mononuclear cells may potentiate
      interstitial fibrosis in vivo by stimulating neovascularization, which leads to
      early fibrotic changes and poor outcome.

PMID- 11840377
TI  - Changes in thyroxine requirements in patients with hypothyroidism undergoing
      renal transplantation.
AB  - Hypothyroidism is common in the renal failure population and is both influenced
      by the onset of renal failure and its correction with renal transplantation. We
      report a series of 20 consecutive patients on oral thyroxine, in which
      restoration of renal function following transplantation resulted in reduced
      thyroxine requirements. We speculate that iodide excess, reduced bioavailability,
      and drug interactions may have contributed both to their hypothyroidism and the
      increased requirements for thyroxine in these patients while on dialysis. Failure
      to recognize the changes following renal transplantation may result in
      significant morbidity.

PMID- 11840378
TI  - A population-based, cross-sectional survey of the Zuni Pueblo: a collaborative
      approach to an epidemic of kidney disease.
AB  - Approximately 80% of the Zuni Indians live in Zuni Pueblo in rural New Mexico.
      The Zuni are relatively endogamous and differ culturally and ethnically from
      neighboring tribes. The Zuni Pueblo is experiencing an epidemic of renal disease.
      The prevalence of end-stage renal disease (ESRD) among the Zuni Indians, adjusted
      for age and gender, is 6-fold and 21-fold higher than the prevalence rates for
      Native Americans and European Americans. Almost all Zuni tribal members have a
      relative with ESRD. This has led to strong public support for renal research. In
      response, the Zuni community has partnered with the Indian Health Service (IHS),
      University of New Mexico Health Sciences Center (UNMHSC), Southwest Foundation
      for Biomedical Research (SFBR), Dialysis Clinic Inc (DCI), and the National
      Institutes of Health (NIH) to establish a research consortium, the Zuni Kidney
      Project (ZKP). The goal of the ZKP is to reduce the burden of renal disease in
      the Zuni community. The ZKP combines traditional, population-based, epidemiologic
      methods with modern techniques of population genetics. The foundation of the ZKP
      is a population-based, cross-sectional survey (PBCSS). The PBCSS has 3 specific
      aims: (1) estimate the prevalence of renal disease in Zuni; (2) assess risk
      factors for renal disease susceptibility; and (3) identify participants for
      planned case-control, longitudinal cohort, and family studies designed to
      identify environmental, familial, and genetic risk factors for the susceptibility
      and/or progression of renal disease. Preliminary results of the PBCSS confirm
      that the epidemic of renal disease in Zuni Indians is due to high rates of both
      diabetic and nondiabetic renal disease.

PMID- 11840379
TI  - Body composition and energy metabolism in chronic renal insufficiency.
AB  - Malnutrition and wasting are important determinants of morbidity and mortality in
      patients with chronic renal failure on dialysis. The aim of this study was to
      determine body composition and energy metabolism in patients with chronic renal
      insufficiency before dialysis. We compared 15 patients (9 women and 6 men) with
      chronic renal failure (creatinine, 1.5 to 4.2 mg/dL) with 15 normal subjects pair
      matched for sex, age (renal failure versus normal, 71 +/- 3 years versus 64 +/- 3
      years), height (1.61 +/- 0.02 m versus 1.64 +/- 0.02 m), and weight (64.5 +/- 2.7
      kg versus 66.4 +/- 1.5 kg). Body composition was measured by dual-energy x-ray
      absorptiometry, and total body water was measured by bioelectrical impedance.
      Energy metabolism was determined by indirect calorimetry. The average glomerular
      filtration rate for the patients with chronic renal insufficiency was 23.9 +/-
      2.6 mL/min/1.73 m2. Lean body mass (41.1 +/- 2.0 kg versus 44.5 +/- 2.2 kg; P =
      0.003) and bone mineral content (2.35 +/- 0.11 kg versus 2.72 +/- 0.12 kg; P =
      0.007) were significantly lower in chronic renal insufficiency; however, fat body
      mass was the same (19.9 +/- 2.1 kg versus 19.1 +/- 1.4 kg; P = 0.68). Total body
      water was similar in renal failure (33.4 +/- 1.5 L versus 34.4 +/- 1.3 L; P =
      0.13). Basal energy expenditure was significantly lower in chronic renal
      insufficiency (1,085 +/- 50 kcal/24 hours versus 1,280 +/- 54 kcal/24 hours; P =
      0.02), even after adjustment for the differences in lean body mass. Daily caloric
      intake indicated energy intake was similar in the patients with chronic renal
      insufficiency and the controls. Patients with a relatively modest degree of
      chronic renal insufficiency are characterized by reduced lean body mass, bone
      mineral content, and basal energy expenditure. The determinants of lean body mass
      in chronic renal insufficiency require further investigation.

PMID- 11840380
TI  - Cigarette smoking predicts faster progression of type 2 established diabetic
      nephropathy despite ACE inhibition.
AB  - Blood pressure reduction and angiotensin-converting enzyme (ACE) inhibitors slow
      but do not stop progressive decline of renal function in established diabetic
      nephropathy (DN), but predictors of this decline in patients undergoing these
      interventions are unknown. We prospectively examined patients to determine
      whether age, sex, ethnicity, mean blood pressure, plasma creatinine, urine
      protein excretion, and cigarette smoking predict renal function decline in type 2
      DN treated toward the recommended mean blood pressure goal of 92 mm Hg (about
      125/75 mm Hg) with antihypertensives including ACE inhibitors. Thirty-three DN
      patients with initial plasma creatinine less than 1.4 mg/dL were followed 64.0 +/
      1.1 months. After correcting for differences in follow-up time, demographic
      variables, and other relevant variables, plasma creatinine increased, indicating
      renal function decline despite mean blood pressure reduction to 92 +/- 1 mm Hg
      and administration of ACE inhibitors. Regression analysis showed that smoking was
      the only examined parameter that significantly predicted renal function decline.
      Smokers (n = 13) and nonsmokers (n = 20) had similar follow-up (61.4 +/- 2.1
      months versus 65.7 +/- 1.1 months), mean blood pressure (91 +/- 1 mm Hg versus 92
      +/- 1 mm Hg), and initial plasma creatinine (1.05 +/- 0.08 mg/dL versus 1.08 +/-
      0.03 mg/dL). Nevertheless, follow-up plasma creatinine was higher in smokers than
      nonsmokers (1.78 +/- 0.20 mg/dL versus 1.32 +/- 0.04 mg/dL). The data show that
      renal function declines faster in smokers than nonsmokers with type 2 DN
      undergoing treatment to improve blood pressure including ACE inhibitors.
      Cigarette smoking remains a risk factor for renal function decline in type 2 DN
      despite currently recommended therapy.

PMID- 11840381
TI  - Dosage of potassium citrate in the correction of urinary abnormalities in
      pediatric distal renal tubular acidosis patients.
AB  - Potassium citrate is an alkaline agent that has been recommended for the
      prevention of nephrolithiasis in distal renal tubular acidosis (RTA). Information
      on the effectiveness and the optimal dose of potassium citrate in the correction
      of urinary abnormalities in pediatric distal RTA is limited, however. We
      conducted this study to determine the effectiveness and the optimal dose of
      potassium citrate for the correction of urinary abnormalities and the prevention
      of nephrolithiasis in children with distal RTA. Eight pediatric distal RTA
      patients participated in this study. The mean +/- SEM age was 9.7 +/- 1.2 years,
      and mean body weight was 29.1 +/- 4.7 kg. After initial evaluation, all patients
      were treated with increasing dosages of potassium citrate starting from 2
      mEq/kg/d in three divided doses. The dosage was increased progressively in a
      stepwise fashion every 2 months from 2 mEq/kg/d to 3 mEq/kg/d, then to 4
      mEq/kg/d. Blood and 8-hour overnight urine samples were obtained at baseline and
      every 2 months before increasing the dosage of potassium citrate. Urinary
      saturations for calcium oxalate and calcium phosphate were estimated by using
      Tiselius's indices. The basal urinary calcium-to-creatinine, phosphate-to
      creatinine, and calcium-to-citrate ratios and urinary saturation for calcium
      oxalate and calcium phosphate were elevated significantly, whereas citrate-to
      creatinine ratio was reduced significantly in distal RTA patients. These ratios
      were normalized gradually with the increasing dosage of potassium citrate. All
      the aforementioned abnormalities were normalized only after the dosage of
      potassium citrate was raised to 4 mEq/kg/d. The elevation in urinary saturation
      of calcium phosphate could not be normalized throughout the study, however. These
      results suggest that 4 mEq/kg/d of potassium citrate supplement can correct
      successfully most of the urinary abnormalities and the elevated urinary
      saturation for calcium oxalate but not for calcium phosphate in children with
      distal RTA. Monitoring of urinary calcium-to-creatinine ratio or citrate-to
      creatinine ratio is valuable to ensure adequate potassium citrate supplementation
      in this group of patients.

PMID- 11840382
TI  - Changes in urinary excretion of six biochemical parameters in normotensive
      pregnancy and preeclampsia.
AB  - We evaluated renal functions by urinary biochemical parameters in normotensive
      pregnancy and preeclampsia. The parameters are expected to be altered resulting
      from different abnormalities of renal glomeruli and tubules. We chose N-acetyl
      beta-d-glucosaminidase (NAG), beta2-microglobulin (beta2MG), total protein (TP),
      albumin (Alb), urea nitrogen (UN), uric acid (UA), and creatinine (Cr). Urinary
      excretion of these biochemical parameter concentrations (relative to Cr) was
      measured simultaneously in first morning fasting urine samples from 27 healthy
      nonpregnant women (group 1), 32 women with normotensive pregnancies (group 2),
      and 26 women with preeclampsia (group 3). The average gestational age at entry
      was 36 weeks. Serum UN and serum UA also were measured. All the ratios were
      significantly higher in group 2 than in group 1. The NAG-to-Cr, TP-to-Cr, and Alb
      to-Cr ratios were significantly higher in group 3 than in group 2. In contrast,
      the UN-to-Cr and UA-to-Cr ratios were significantly lower in group 3 than in
      group 2. The percent increase in the beta2MG-to-Cr ratio in group 2 relative to
      that in group 1 was the highest, followed by percent increases in the NAG-to-Cr,
      TP-to-Cr, Alb-to-Cr, UA-to-Cr, and UN-to-Cr ratios. In contrast, the percent
      increase in the Alb-to-Cr ratio in group 3 relative to that in group 2 was the
      highest, followed by percent increases in the TP-to-Cr, NAG-to-Cr, beta2MG-to-Cr,
      UA-to-Cr, and UN-to-Cr ratios. The percent increases in the NAG-to-Cr and beta2MG
      to-Cr ratios rose markedly in normotensive pregnancy, whereas percent increases
      of the Alb-to-Cr and TP-to-Cr ratios were far greater in preeclampsia than in
      normotensive pregnancy. Renal tubular damage and reabsorption dysfunction may be
      impaired markedly even in normotensive pregnancy, and further deterioration in
      reabsorption dysfunction may be slight in preeclampsia. Renal glomerular
      permeability of TP and Alb may be enhanced in normotensive pregnancy and markedly
      enhanced in preeclampsia.

PMID- 11840383
TI  - Primary IgA nephropathy with low histologic grade and disease progression: is
      there a "point of no return"?
AB  - Histologic low-grade chronic renal lesions in 144 adults with primary
      immunoglobulin A (IgA) nephropathy were correlated with clinical parameters of
      disease progression over a median follow-up of 93 months. Using chronicity-based
      histologic grading, 50, 59, and 35 patients were glomerular grade (GG) 1a, GG1b,
      and GG2; 83 and 61 patients were tubulointerstitial grade (TIG) 1 and TIG2; and
      25 patients had hyaline arteriolosclerosis. On follow-up, GG and TIG were
      predictive of disease progression by impairment of renal function, development of
      hypertension, and significant proteinuria (>1 g/d). Hyaline arteriolosclerosis
      correlated only with the development of hypertension. Histologic lesions GG1a or
      TIG1 predicted a significant low risk for disease progression compared with other
      renal lesions, regardless of the renal manifestation at the time of biopsy.
      Combined GG1a, TIG1, and isolated hematuria at the time of biopsy enhanced the
      sensitivity to determine early IgA nephropathy and to define a nonearly cohort
      with a higher risk of disease progression appropriate for recruitment into
      clinical therapeutic trials within realistic time frames. The significant risk of
      progression in other low-grade lesions, such as GG1b or TIG2, suggests that the
      point of no return in IgA nephropathy may occur much earlier than perceived and
      that delayed biopsy in these patients no longer may be justified.

PMID- 11840384
TI  - CD44 expression in IgA nephropathy.
AB  - Immunoglobulin A (IgA) nephropathy is a frequent, chronic renal disease
      characterized by a broad spectrum of clinical presentations and pathologic
      findings. CD44, a family of type I transmembrane glycoproteins involved in cell
      cell and cell-matrix interactions, may orchestrate partially the cascade of
      inflammation, accumulation of myofibroblasts, and fibrosis leading to end-stage
      renal disease. To clarify the possible role of CD44 in the progression of IgA
      nephropathy, the expression of CD44 in glomeruli and the tubulointerstitial
      compartment was analyzed in 25 renal biopsy specimens of patients with IgA
      nephropathy and was correlated to histopathologic, serologic, and urinary
      parameters. The expression of CD44 correlated significantly with the degree of
      glomerular and interstitial damage, even better than the accumulation of alpha
      smooth muscle actin-positive myofibroblasts, which is recognized as a reliable
      marker for the progression of IgA nephropathy. A positive correlation also was
      found between proteinuria and the expression of CD44 in the tubulointerstitial
      compartment. The glomerular and tubulointerstitial expression of CD44 correlated
      with the degree of renal damage in IgA nephropathy and could be a reliable marker
      of the progression of IgA nephropathy. CD44 may have a pivotal role in the
      cascade of renal inflammation and fibrosis.

PMID- 11840385
TI  - Treatment of systemic lupus erythematosus by immunoadsorption in a patient
      suffering from tuberculosis.
AB  - We report on a 40-year-old man, admitted with fever and weight loss, in whom
      systemic lupus erythematosus (lupus nephritis World Health Organization type IV)
      and concomitant acute lung tuberculosis were diagnosed. Conventional treatment of
      diffuse proliferative nephritis with cytotoxic drugs was thought to be too
      dangerous in the presence of active tuberculosis. A combination of
      immunoadsorption and steroids was instituted for the treatment of systemic lupus
      erythematosus. Antibodies against double-stranded DNA decreased, and proteinuria
      decreased from 10 g/24 hours to less than 1 g/24 hours. Tuberculosis was treated
      initially with quadruple-drug therapy, then a triple-drug protocol. Primarily
      enlarged lymph nodes decreased to normal size after 3 months. The combined
      treatment modality of steroids and immunoadsorption was effective and safe, even
      in this patient with active tuberculosis.

PMID- 11840386
TI  - Safety and efficacy of simvastatin in patients undergoing chronic renal dialysis:
      are we ready to treat hypercholesterolemia?

PMID- 11840387
TI  - What are the causes of protein-energy malnutrition in chronic renal
      insufficiency?

PMID- 11840388
TI  - Just the FAQs: frequently asked questions about iron and anemia in patients with
      chronic kidney disease.

PMID- 11840389
TI  - An 11-year-old African-American girl with systemic lupus erythematosus and ANCA
      negative renal vasculitis.

PMID- 11840392
TI  - Nonconvulsive status epilepticus in dialysis patients.

PMID- 11840393
TI  - Is vitamin D receptor gene polymorphism an independent predictor of mortality in
      hemodialysis patients?

PMID- 11840394
TI  - Gender differences in responsiveness to erythropoietin.

PMID- 11840397
TI  - Diagnosis of pheochromocytoma and laparoscopic adrenalectomy in two anephric
      patients with von Hippel-Lindau disease.
AB  - This study reports the first two cases of laparoscopic treatment of functional
      pheochromocytomas in patients with von Hippel-Lindau (VHL) disease receiving
      regular dialysis treatment. The genetic changes predisposing to pheochromocytoma,
      diagnostic procedures, and surgical management were analyzed. Both patients were
      considered at low risk of developing pheochromocytoma because they belonged to
      VHL families with 10 and 25 affected relatives without pheochromocytoma (VHL type
      1 families). The mutation responsible for the disease was a stop codon in one
      case and a missense change in the other. Multiple renal cell carcinomas had
      required removal of the kidneys at age 37 in one patient and age 25 in the other
      patient. Computed tomography scan was crucial for diagnosis, showing a unilateral
      enlarged adrenal gland after 3 and 6 years on regular dialysis. No change in
      blood pressure was observed. MIBG scintigraphy was negative. Plasma epinephrine
      in one case and dopamine in the other were increased compared with patients on
      hemodialysis without pheochromocytoma. Pheochromocytomas were removed
      successfully by laparoscopic adrenalectomy. Lifelong follow-up of all affected
      tissues is required in all VHL patients, and pheochromocytoma should be screened
      for even in the absence of family history in large kindreds. Computed tomography
      scan allows early recognition, and patients on hemodialysis are responsive to
      laparoscopic adrenalectomy.

PMID- 11840399
TI  - Hypercalcemia in a renal transplant recipient suffering with Pneumocystis carinii
      pneumonia.
AB  - Hypercalcemia occurs frequently after renal transplantation. Preexisting
      hyperparathyroidism is the most common cause of post-transplantation
      hypercalcemia. We describe a renal transplant recipient infected with
      Pneumocystis carinii pneumonia (PCP) who developed hypercalcemia, elevated 1,25
      dihydroxyvitamin D, and suppressed parathyroid hormone levels. This phenomenon
      mimics the extrarenal production of 1,25-dihydroxyvitamin D by activated alveolar
      macrophages in granulomatous diseases with hypercalcemia. To the best of our
      knowledge, this is the first report of 1,25-dihydroxyvitamin D-mediated
      hypercalcemia caused by PCP in a renal transplant recipient. This entity should
      be included in the differential diagnosis for renal transplant recipients with
      hypercalcemia, especially in patients who develop lung infections.

PMID- 11840398
TI  - Medical management of pneumonia caused by Rhodococcus equi in a renal transplant
      recipient.
AB  - Rhodococcus equi is an animal pathogen that occasionally causes opportunistic
      infections in immunocompromised patients. The most common clinical picture is one
      of necrotizing pneumonia with a tendency toward cavitation and the formation of
      abscesses. We report a case of pneumonia caused by R equi in a renal transplant
      patient. An excellent response was shown to antibiotic treatment. Symptoms
      regressed, and the progressive disappearance of the lesion was confirmed on
      follow-up computed tomography scans. Surgical intervention or other invasive
      procedures were not required. To our knowledge, 14 cases of infection by R equi
      in solid-organ transplant patients have been described to date. Nine were
      recipients of a renal allograft. Surgery was required in many of these patients,
      and all the renal transplant recipients required the use of invasive therapeutic
      techniques, such as pleural drainage. This is the first case of a renal
      transplant recipient in whom radiologic presentation was as a solid nodule
      without ensuing cavitation that resolved exclusively with antibiotic treatment.

PMID- 11840400
TI  - Retransplantation in a patient with type 2 Jeune's syndrome.
AB  - Jeune's syndrome is a rare inherited cause of kidney failure associated with
      skeletal dysplasia in children. We report the case of a 20-year-old girl who had
      Jeune's syndrome type 2 and underwent a second kidney transplant after failure of
      the first allograft. The patient had 16 years of good allograft function with the
      first transplant and successfully received a second cadaveric graft.

PMID- 11840401
TI  - Pharmacokinetics of 5-fluorouracil and its catabolites determined by 19F nuclear
      magnetic resonance spectroscopy for a patient on chronic hemodialysis.
AB  - 5-fluorouracil (5-FU), widely used for chemotherapy of colorectal carcinoma,
      requires intracellular anabolic conversion to cytotoxic nucleotides and exhibits
      a narrow therapeutic range with dose-dependent and concentration-dependent
      effects. 5-FU undergoes extensive metabolic degradation to several catabolites,
      which are excreted mainly by the kidneys. Alteration of the pharmacokinetics of 5
      FU and its catabolites as a result of renal dysfunction might augment systemic
      toxicity. Because no data are available for patients with severe renal failure,
      the pharmacokinetic parameters of 5-FU and its catabolites were determined for a
      patient with colorectal carcinoma and end-stage renal disease on maintenance
      hemodialysis therapy. Plasma was analyzed by 19F nuclear magnetic resonance
      spectroscopy for the first 5-day treatment cycle (daily bolus injections of 5-FU
      for 5 days in combination with low-dose folinic acid). On days 1 and 5, the
      pharmacokinetic parameters for 5-FU (total area under the plasma concentration
      time curve, terminal half-life, total plasma clearance, volume of distribution
      based on the terminal phase) and its initial catabolite dihydrofluorouracil
      (total area under the plasma concentration-time curve, terminal half-life) were
      in the ranges reported in the literature for patients with normal renal function,
      implying no need for primary dose adjustment. In contrast, the final 5-FU
      catabolite alpha-fluoro-beta-alanine (FBAL) accumulated to a concentration of 276
      micromol/L on day 5 (approximately twofold higher than expected from the
      literature) despite good removal by hemodialysis with extraction ratios of 0.6 to
      0.85 over the filter membrane. Negative effects of FBAL or enhancement of 5-FU
      related toxicity could not be judged in this individual case, but further study
      is warranted to determine the possible benefits of more intensive dialysis
      treatment.

PMID- 11840402
TI  - A case of late-onset primary hyperoxaluria type 1.
AB  - Primary hyperoxaluria type 1 (PH1) is an inherited metabolic disorder
      characterized by recurrent urolithiasis and nephrocalcinosis frequently leading
      to progressive renal insufficiency during the second decade of life. Systemic
      organ involvement as a result of the accumulation of calcium oxalate crystal
      deposits in vessel walls often is observed. We report a case of a 56-year-old
      woman with late-onset of PH1 who developed rapidly progressive renal failure and
      severe systemic oxalosis with skin and eye involvement despite intensified
      hemodialytic therapy during the waiting period for combined liver and kidney
      transplantation. This case illustrates the difficulties in treatment of PH1
      induced end-stage renal disease. Combined liver and kidney transplantation should
      be offered to these patients as soon as possible to reverse the underlying
      metabolic defect and to restore renal function.

PMID- 11840403
TI  - Research beyond September 11...everything changes.

PMID- 11840404
TI  - Memory improvement in octogenarians.
AB  - This pre-post quasiexperimental study tested the eight-session Cognitive
      Behavioral Model of Everyday Memory in residents (58 women, 20 men) of a
      retirement village in Northeast Ohio. Their average age was 82 years, with 16
      years of education and Mini-Mental State Examination score of 28; 13% were
      depressed. All participants were pretested and posttested at 8 weeks. The largest
      gains were in memory self-efficacy and use of internal memory strategies.
      Moderate gains were made in instrumental activities and change, and smaller gains
      were made in locus and memory performance. The dose of the intervention (eight
      sessions) was adequate, and practice in each class session facilitated mastery of
      memory strategies and techniques.

PMID- 11840405
TI  - Patient identification of caregivers' titles: do they know who you are?
AB  - This study investigated patients' abilities to identify licensed nurse and
      unlicensed assistive personnel (UAP) and whether this knowledge is related to
      satisfaction with care. Of 100 patients from two hospitals, 28% did not know
      whether caregivers were nurses or UAP on sight. Fifteen percent of patients asked
      to identify UAP assumed that the caregiver was a nurse. Patients could not
      recognize their nurse or UAP caregivers 59% of the time from a list of names.
      Patients were three times more likely to know the names and titles of their
      nurses. Older patients were less likely to remember the names and titles of their
      caregivers. Satisfaction with nursing care was not predicted by patients'
      knowledge of caregiver name or title.

PMID- 11840406
TI  - Preoperative physical activity, anesthesia, and analgesia: effects on early
      postoperative walking after total hip replacement.
AB  - This study explored whether preoperative activity, anesthesia, or analgesia
      influence early postoperative walking after total hip replacement (THR). Data
      were collected as part of a randomized intervention study of standard or
      augmented postoperative activity and its influence on wound healing. More than
      half of all subjects did not exercise regularly. Subjects who performed strength
      activities preoperatively walked significantly greater distances. Anesthesia or
      analgesia did not affect walking distances. Upper arm strength is needed after
      THR because walking is dependent on the use of assistive devices. These results
      suggest: (1) preoperative exercise may promote recovery of mobility after THR,
      and (2) a need to evaluate preoperative exercise programs for effect on mobility
      and independence after THR.

PMID- 11840407
TI  - Comparison of normal saline and heparinized saline for patency of IV locks in
      neonates.
AB  - In this randomized double-blind experiment of 49 neonatal intensive care unit
      patients, probable time to catheter failure was significantly longer (p =.0358)
      for catheters flushed with heparinized saline (median = 127) compared with those
      flushed with normal saline (median = 39). This is in contrast to the
      nonsignificant difference (p =.841) in mean scores for six heparin-flushed
      catheters (M = 41.5 hours, SD = 44.0) compared with 18 saline-flushed catheters
      (M = 30.4 hours, SD = 20.8) discontinued for reasons other than completion of
      treatment. We concluded that survival time analysis is necessary when evaluating
      results of time-dependent studies in which the end point may not be elective.

PMID- 11840408
TI  - Reciprocity and retaining African-American women with HIV in research.
AB  - Retaining African-American women who are human immunodeficiency virus (HIV)
      positive in longitudinal research is crucial to improving prevention and
      treatment in this population. Interviews with 22 African-American HIV-positive
      women conducted at the end of a 2-year study indicated that over the course of
      the study, reports of discomfort with participation gave way to reports of
      appreciating the benefits of participation. Women commented on the importance of
      their relationships with researchers, in which they received benefits and
      provided a service to the researchers. We postulate that developing reciprocity
      between research teams and participants may be helpful in retaining African
      American women in research.

PMID- 11840409
TI  - Comparison of oral and tympanic temperatures in adult surgical patients.
AB  - Monitoring patients' temperatures is an important aspect of clinical nursing. In
      surgical areas, we rely on accurate temperature readings to determine appropriate
      therapy. Various body sites have been used for temperature measurement: oral,
      axillary, rectal, and tympanic. Oral temperature readings have long been
      considered the gold standard. However, oral temperature readings may be
      contraindicated, depending on surgical incision and level of consciousness or in
      cases of seizure. Tympanic temperature monitoring is often the next choice. The
      literature supports the accuracy of tympanic monitoring; however, some clinicians
      have questioned its accuracy. This study used a repeated-measures design to
      determine the reproducibility of tympanic and oral temperature measurements. A
      difference of 0.2 degrees C was considered clinically significant. Outcome data
      indicated that variability was similar with oral and tympanic temperatures. There
      was no significant difference between average tympanic and average oral
      temperatures. Therefore, this study supports the use of tympanic thermometers in
      addition to oral thermometers in obtaining temperatures.

PMID- 11840410
TI  - Nursing Care Quality Initiative (NCQI) for hospitalized elders and their
      families: a demonstration and quality improvement model of nursing care.

PMID- 11840411
TI  - What is a systemic review?

PMID- 11840412
TI  - A compendium of innovative nursing leadership projects: the American Organization
      of Nurse Executives' 2001 poster presentations.

PMID- 11840413
TI  - Surgical management of ovarian cancer.
AB  - The management of ovarian cancer presents one of the greatest challenges to
      physicians caring for patients with cancer. The treatment almost always involves
      a combination of surgery and chemotherapy. Over the past 75 years we have formed
      a rational system for the surgical management of this disease. Initial surgical
      therapy should include the following three objectives: (1) staging, (2)
      cytoreduction, and (3) determining a definitive histologic diagnosis. The
      importance of meticulous staging cannot be overstated. Fully one third of
      patients not compulsively staged will be upstaged if surgically restaged.
      Cytoreductive surgery is the mainstay of initial treatment. Data clearly
      demonstrate that ovarian cancer is different from other solid tumors in that
      reduction of the tumor burden is important in the management of this disease.
      Patients with less than 1 to 2 cm of disease remaining at the conclusion of
      initial surgery have a survival advantage over those who do not. The benefits of
      secondary cytoreduction are less clear, and data support the concept of
      cytoreduction in many circumstances. These surgical issues surrounding ovarian
      cancer support the concept that physicians trained to treat ovarian cancer be
      involved in its management. Data are emerging that clearly suggest that
      gynecologic oncologists should be involved in both the surgical and medical
      management of patients with ovarian cancer.

PMID- 11840414
TI  - Second-line treatment of ovarian cancer with single-agent gemcitabine.
AB  - Single-agent gemcitabine has been examined in several phase II trials in platinum
      and paclitaxel-resistant advanced ovarian cancer. In this population, where
      patients are often heavily pretreated prior to the administration of gemcitabine,
      an acceptable dose and schedule is 800 to 1,000 mg/m(2) weekly for 3 weeks,
      followed by a 1-week rest. The anticipated objective response rate in the
      platinum/taxane-resistant population is approximately 15%. This level of activity
      (confirmed in several phase II trials), and the generally favorable toxicity
      profile for gemcitabine in this group of patients, leads to the conclusion that
      single-agent gemcitabine is a reasonable second-line treatment option in
      previously treated women with advanced ovarian cancer.

PMID- 11840415
TI  - The role of gemcitabine-based doublets in the management of ovarian carcinoma.
AB  - Efforts to improve further therapy for advanced ovarian carcinoma currently focus
      on addition of a third active agent to front-line chemotherapy. Three agents with
      activity against disease clinically resistant to paclitaxel and the platinum
      compounds are of greatest interest: gemcitabine, topotecan, and liposome
      encapsulated doxorubicin. Three strategies to add a third agent include a triplet
      regimen that adds a third agent concurrently; a sequential doublet regimen giving
      three to four cycles of the new agent plus a platinum followed by three to four
      cycles of paclitaxel plus a platinum; and sequential single agents consisting of
      three to four cycles of the new agent with three to four cycles each of
      paclitaxel and a platinum. Gemcitabine in combination with another agent has been
      evaluated to develop doublet regimens for the second of these three strategies.
      Combinations both feasible and active include gemcitabine plus cisplatin or
      carboplatin, gemcitabine plus paclitaxel, gemcitabine plus topotecan, gemcitabine
      plus liposome-encapsulated doxorubicin, gemcitabine plus vinorelbine, and
      gemcitabine plus treosulfan. The combinations of gemcitabine plus a platinum
      compound appear most promising with synergism suggested by the data. A
      gemcitabine/carboplatin doublet for four cycles followed by four cycles of
      paclitaxel/carboplatin is currently under evaluation in a randomized phase III
      trial (Gynecologic Oncology Group [GOG] protocol 0182).

PMID- 11840416
TI  - Gemcitabine, platinum, and paclitaxel regimens in patients with advanced ovarian
      carcinoma.
AB  - In advanced ovarian cancer, gemcitabine is a candidate for combination
      chemotherapy due to its unique mechanism of action, favorable toxicity profile,
      and proven activity. Gemcitabine, paclitaxel, and platinum have demonstrated a
      response rate of 100% in patients with relapsed ovarian cancer. The median time
      to progression was 10 months and the median survival was more than 27 months. Two
      trials with gemcitabine, paclitaxel, and carboplatin in previously untreated
      patients, including 24 and 13 evaluable patients, respectively, have both
      demonstrated 100% response rates. A complete remission (CR) rate of 60% has been
      described in one trial, and the median time to progression in this trial was 16
      months. The median survival has not been reached but is more than 30 months. In
      conclusion, gemcitabine, paclitaxel, and carboplatin is a very active combination
      in previously untreated patients with advanced ovarian cancer. Ongoing and future
      randomized trials will show whether or not this finding translates into improved
      survival.

PMID- 11840417
TI  - Developmental chemotherapy in advanced ovarian cancer: incorporation of newer
      cytotoxic agents in a phase III randomized trial of the Gynecologic Oncology
      Group (GOG-0182).
AB  - Despite improvements in median and overall survival using a combination of
      platinum and paclitaxel, long-term survival rates for patients with advanced
      epithelial ovarian carcinoma (EOC) remain disappointing, and the development of
      more effective primary therapy remains a priority. In particular, several
      interesting chemotherapy agents have demonstrated activity individually in
      patients with recurrent EOC. Among these are gemcitabine, topotecan, liposomal
      doxorubicin, and prolonged oral etoposide. Preclinical models have suggested an
      advantage for combinations of these agents with platinum, which has been
      attributed to inhibition of DNA synthetic pathways involved in the repair of
      platinum-DNA adducts. However, efforts to develop multidrug combinations with
      platinum and paclitaxel have encountered substantial bone marrow toxicity,
      prompting exploration of alternative schedules and sequences of drug
      administration. In this regard, the Gynecologic Oncology Group (GOG) and other
      organizations have conducted a series of phase I pilot studies in previously
      untreated patients to define combinations that are suitable for group-wide phase
      III trials. With international collaboration, GOG has launched a five-arm trial
      (GOG-0182) that will compare these combinations against carboplatin-paclitaxel.
      The selection of candidate regimens for this trial illustrates the challenges of
      drug development in EOC.

PMID- 11840418
TI  - Future directions in the treatment of ovarian cancer.
AB  - Standard chemotherapy for previously untreated patients with advanced ovarian
      cancer consists of the combination of a taxane and a platinum compound. While the
      majority of patients respond to therapy, median time to progression is less than
      2 years. Patients with recurrent disease frequently respond to second-line
      treatments, but the impact on survival remains uncertain. Consequently, new
      treatment approaches are needed. Based on the results of phase II trials that
      demonstrated activity in previously treated patients with ovarian cancer, new
      combination regimens are being tested in which drugs such as gemcitabine,
      topotecan, or encapsulated doxorubicin are added to or sequenced with carboplatin
      plus paclitaxel. In addition, new platinum and taxane analogs are also under
      clinical development. Biological approaches to the treatment of patients with
      ovarian cancer are also in clinical development and include drugs that interfere
      with angiogenesis, matrix metalloproteinases, and signal transduction pathways.
      These drugs are currently being tested in previously treated patients with
      recurrent ovarian cancer. However, ultimately there may be a new paradigm of
      treatment in which patients receive combination chemotherapy together with a
      biologic agent for six cycles of treatment and, at that point, the chemotherapy
      is stopped and patients continue with chronic maintenance biologic therapy. Semin
      Oncol 29 (suppl 1):32-42.

PMID- 11840419
TI  - Overview: the management of lower extremity venous problems.

PMID- 11840420
TI  - The epidemiology, pathophysiology, and natural history of chronic venous disease.
AB  - Chronic venous disease includes a spectrum of clinical presentations ranging from
      varicose veins through chronic lower extremity pain and edema to venous skin
      changes and ulceration. Such manifestations may result from primary venous
      insufficiency or be secondary to other disorders, primarily acute deep venous
      thrombosis. Regardless of etiology, chronic venous disease has significant
      socioeconomic consequences and is among the most common problems encountered in
      surgical practice. Ambulatory venous hypertension underlies most of the sequelae
      of chronic venous disease, although such hemodynamic derangements may result from
      either valvular incompetence or venous obstruction. Unfortunately, the factors
      responsible for the progression of disease from mild to severe manifestations are
      only beginning to be understood. However, a thorough understanding of the
      pathophysiology and natural history of chronic venous disease is essential in its
      management.

PMID- 11840421
TI  - PPG, APG, duplex: which noninvasive tests are most appropriate for the management
      of patients with chronic venous insufficiency?
AB  - Numerous noninvasive tests have been described for assistance in the diagnosis
      and treatment of patients with chronic venous insufficiency (CVI). These tests
      include venous duplex ultrasound examination in the supine and standing
      positions, photoplethysmography (PPG), and air plethysmography (APG). The goal of
      these studies is to provide accurate information describing the anatomic or the
      hemodynamic characteristics of the patient with CVI, precluding the need for
      invasive studies. These tests will be reviewed including the typical information
      obtained, the usefulness of this information, and the relevance for clinical
      management of patients with CVI. Based on the clinical class, recommendations for
      a noninvasive testing protocol are outlined.

PMID- 11840422
TI  - Varicose veins: hooks, clamps, and suction. Application of new techniques to
      enhance varicose vein surgery.
AB  - Surgical principles that guided varicose vein surgery for nearly 75 years have
      been time honored and taught to generations of surgeons. Each of these principles
      has been challenged successfully, and, as a result, varicose vein surgery has
      changed markedly. The fundamental principle of totally removing varicose clusters
      from the circulation remains firmly established. However, methods of
      accomplishing this have changed and continue to change. Hook phlebectomy and
      clamp phlebectomy have replaced open dissection and tributary ligation. The place
      of tumescent anesthesia, transilluminated-powered phlebectomy, and sclerotherapy
      remain unsettled. However, there now are a number of alternatives in planning
      patient care.

PMID- 11840423
TI  - Conservative hemodynamic surgery for varicose veins.
AB  - Conservative hemodynamic surgery for varicose veins is a minimally invasive,
      nonablative technique that preserves the saphenous vein and helps avoid excision
      of varicosities. It represents a physiologic approach to the surgical treatment
      of varicose veins based on knowledge of the underlying venous pathophysiology
      gained through detailed duplex scanning. A change in venous hemodynamics is
      attained through fragmentation of the blood column by interruption of the
      refluxing saphenous trunks, closure of the origin of the refluxing varicose
      branches, and preservation of the communicating veins that drain the incompetent
      varicose veins into the deep venous system. After surgery, varicose veins regress
      through a reduction in hydrostatic pressure and efficient emptying of the
      superficial system by the musculo-venous pump. Obvious advantages of this
      technique are that it is done in an ambulatory setting, minimizes the risk of
      surgical complications, and permits a rapid return to full activity. The long
      term hemodynamic improvement and recurrence rate of this technique remain to be
      established.

PMID- 11840424
TI  - Radiofrequency ablation of the long saphenous vein without high ligation versus
      high ligation and stripping for primary varicose veins: pros and cons.
AB  - Primary varicose vein disease is prevalent in our society, and although it is
      infrequently the cause of serious venous insufficiency, it often is associated
      with symptoms of local discomfort. These symptoms eventually may outweigh any
      cosmetic concerns of patients with this disease. Greater saphenous vein (GSV)
      reflux is the most important pathophysiologic component of primary venous
      insufficiency. To date, the surgical treatment of GSV reflux has evolved into 1
      of 3 procedures: high ligation of the saphenofemoral junction, with or without
      perforator ligation; high ligation and stripping of the GSV; and high ligation
      with retrograde sclerotherapy of the GSV. High ligation and stripping of the GSV
      to below the knee enjoys the most durable success yet is associated with
      significant perioperative morbidity. A new treatment, radiofrequency ablation of
      the GSV without high ligation, recently has been described and promises a less
      invasive alternative to stripping with decreased morbidity and increased patient
      acceptance. The results of high ligation and stripping of the GSV will be
      compared with those with radiofrequency ablation of the GSV without high
      ligation.

PMID- 11840425
TI  - Subfascial endoscopic perforator vein surgery: who benefits?
AB  - The advent of minimally invasive endoscopic surgery has rekindled interest in
      perforator vein ligation. Subfascial endoscopic perforator vein surgery (SEPS)
      utilizes techniques to interrupt incompetent perforators under direct vision
      using an endoscopic videocamera and instrumentation placed through small ports
      remote from the active ulcer or area of diseased skin. The safety and early
      efficacy of SEPS has been established in several studies, and it yields lower
      wound complication rates than observed with open surgical techniques such as the
      Linton procedure. Available results confirm the superiority of SEPS over open
      perforator ligation, but do not address the its role in the surgical treatment of
      advanced chronic venous insufficiency (CVI) and venous ulceration. Ablation of
      superficial reflux by high ligation and stripping of the greater saphenous vein
      with avulsion of branch varicosities is concomitantly performed in the majority
      of patients undergoing SEPS. The clinical and hemodynamic improvements
      attributable to SEPS thus are difficult to ascertain. As with open perforator
      ligation, clinical and hemodynamic results are better in patients with primary
      valvular incompetence (PVI) than in those with the postthrombotic (PT) syndrome.
      Until prospective, randomized, multicenter clinical trials are carried out to
      answer lingering questions regarding the efficacy of SEPS, the procedure is
      recommended in patients with advanced CVI secondary to PVI of superficial and
      perforating veins, with or without deep venous incompetence. The performance of
      SEPS in patients with PT syndrome remains controversial.

PMID- 11840426
TI  - Surgical management of deep venous reflux.
AB  - Axial deep venous reflux can be found in the majority of extremities with
      advanced skin changes and ulceration. It frequently is associated with recurrent
      disease and tends to progress with time. More than 30 years' experience with deep
      venous reconstructive surgery, as well as recent advances in diagnostic imaging,
      makes possible the rational use of such techniques in the management of chronic
      venous insufficiency. This report reviews the role of deep venous reflux in the
      natural history and progression of venous disease, the options for surgical
      correction of deep venous reflux, the current diagnostic abilities and
      limitations, and the results of surgical interventions.

PMID- 11840427
TI  - Proximal lower extremity chronic venous outflow obstruction: recognition and
      treatment.
AB  - As postthrombotic disease becomes better understood, the importance of venous
      outflow obstruction is recognized increasingly. It appears that obstruction of
      the iliac vein is particularly important and results in more severe symptoms than
      more distal segmental blockages. Unfortunately, no accurate invasive or
      noninvasive test for the evaluation of obstruction is available. In fact, it is
      not known what degree of venous stenosis should be considered hemodynamically
      "critical." Thus, currently it is impossible to detect borderline obstructions of
      potential hemodynamic significance. A high index of suspicion must be maintained.
      The diagnosis relies on clinical signs and symptoms, and treatment must be based
      on results of morphologic investigations such as transfemoral phlebography or,
      preferably, intravascular ultrasonography. Percutaneous iliac venous balloon
      dilation and insertion of a stent offers a safe and efficient method to correct
      pelvic venous obstruction. It is less invasive and relatively safer than open
      surgery and can, therefore, be offered to a larger group of patients.
      Furthermore, initial percutaneous management does not preclude subsequent bypass
      or reflux surgery. Although the technique is recent and follow-up relatively
      short, there is cautious optimism that this treatment will be useful and replace
      bypass surgery for iliac venous obstruction.

PMID- 11840428
TI  - Congenital vascular malformations: when and how to treat them.
AB  - Congenital vascular malformations may involve arterial, venous, and lymphatic
      structures, can present in a variety of forms, and present many diagnostic and
      therapeutic challenges. Two-thirds of all congenital vascular malformations are
      predominantly venous, and their management will be emphasized in this article,
      because of the focus of this issue. The majority of the venous malformations are
      asymptomatic and should be treated conservatively. However, the clinical
      presentation of venous malformations associated with lymphatic anomalies is
      variable, and management may be more challenging. The diagnosis and management of
      arteriovenous malformations is straightforward. Selective catheter-directed
      embolization of the feeding arteries, occasionally followed by tumor excision, is
      the treatment of choice. Hemangiomas often will grow rapidly and then begin to
      regress. When they produce troublesome symptoms and are well localized, they
      should be excised. Deeply seated or diffuse malformations require a complete
      diagnostic evaluation to select the most appropriate time and type of
      intervention. Both our own experience and that of others can provided some basis
      for therapeutic recommendations in treating the different vascular malformations.

PMID- 11840429
TI  - Treating rheumatoid arthritis early: a window of opportunity?

PMID- 11840430
TI  - The diagnosis and prognosis of early arthritis: rationale for new prognostic
      criteria.

PMID- 11840432
TI  - How important are T cells in chronic rheumatoid synovitis?: II. T cell
      independent mechanisms from beginning to end.

PMID- 11840431
TI  - Pregnancy and microchimerism in autoimmune disease: protector or insurgent?

PMID- 11840433
TI  - Management of uveitis: a rheumatologic perspective.

PMID- 11840434
TI  - Diagnosing reactive arthritis: role of clinical setting in the value of serologic
      and microbiologic assays.

PMID- 11840435
TI  - Guidelines for the management of rheumatoid arthritis: 2002 Update.

PMID- 11840436
TI  - COBRA combination therapy in patients with early rheumatoid arthritis: long-term
      structural benefits of a brief intervention.
AB  - OBJECTIVE: The Combinatietherapie Bij Reumatoide Artritis (COBRA) trial
      demonstrated that step-down combination therapy with prednisolone, methotrexate,
      and sulfasalazine (SSZ) was superior to SSZ monotherapy for suppressing disease
      activity and radiologic progression of rheumatoid arthritis (RA). The current
      study was conducted to investigate whether the benefits of COBRA therapy were
      sustained over time, and to determine which baseline factors could predict
      outcome. METHODS: All patients had participated in the 56-week COBRA trial.
      During followup, they were seen by their own rheumatologists and were also
      assessed regularly by study nurses; no treatment protocol was specified. Disease
      activity, radiologic damage, and functional ability were the primary outcome
      domains. Two independent assessors scored radiographs in sequence according to
      the Sharp/van der Heijde method. Outcomes were analyzed by generalized estimating
      equations on the basis of intent-to-treat, starting with data obtained at the
      last visit of the COBRA trial (56 weeks after baseline). RESULTS: At the
      beginning of followup, patients in the COBRA group had a significantly lower mean
      time-averaged 28-joint disease activity score (DAS28) and a significantly lower
      median radiologic damage (Sharp) score compared with those in the SSZ monotherapy
      group. The functional ability score (Health Assessment Questionnaire [HAQ]) was
      similar in both groups. During the 4-5 year followup period, the time-averaged
      DAS28 decreased 0.17 points per year in the SSZ group and 0.07 in the COBRA
      group. The Sharp progression rate was 8.6 points per year in the SSZ group and
      5.6 in the COBRA group. After adjustment for differences in treatment and disease
      activity during followup, the between-group difference in the rate of radiologic
      progression was 3.7 points per year. The HAQ score did not change significantly
      over time. Independent baseline predictors of radiologic progression over time
      (apart from treatment allocation) were rheumatoid factor positivity, Sharp score,
      and DAS28. CONCLUSION: An initial 6-month cycle of intensive combination
      treatment that includes high-dose corticosteroids results in sustained
      suppression of the rate of radiologic progression in patients with early RA,
      independent of subsequent antirheumatic therapy.

PMID- 11840437
TI  - How to diagnose rheumatoid arthritis early: a prediction model for persistent
      (erosive) arthritis.
AB  - OBJECTIVE: To develop a clinical model for the prediction, at the first visit, of
      3 forms of arthritis outcome: self-limiting, persistent nonerosive, and
      persistent erosive arthritis. METHODS: A standardized diagnostic evaluation was
      performed on 524 consecutive, newly referred patients with early arthritis.
      Potentially diagnostic determinants obtained at the first visit from the
      patient's history, physical examination, and blood and imaging testing were
      entered in a logistic regression analysis. Arthritis outcome was recorded at 2
      years' followup. The discriminative ability of the model was expressed as a
      receiver operating characteristic (ROC) area under the curve (AUC). RESULTS: The
      developed prediction model consisted of 7 variables: symptom duration at first
      visit, morning stiffness for > or =1 hour, arthritis in > or =3 joints, bilateral
      compression pain in the metatarsophalangeal joints, rheumatoid factor positivity,
      anti-cyclic citrullinated peptide antibody positivity, and the presence of
      erosions (hands/feet). Application of the model to an individual patient resulted
      in 3 clinically relevant predictive values: one for self-limiting arthritis, one
      for persistent nonerosive arthritis, and one for persistent erosive arthritis.
      The ROC AUC of the model was 0.84 (SE 0.02) for discrimination between self
      limiting and persistent arthritis, and 0.91 (SE 0.02) for discrimination between
      persistent nonerosive and persistent erosive arthritis, whereas the
      discriminative ability of the American College of Rheumatology 1987
      classification criteria for rheumatoid arthritis was significantly lower, with
      ROC AUC values of 0.78 (SE 0.02) and 0.79 (SE 0.03), respectively. CONCLUSION: A
      clinical prediction model was developed with an excellent ability to
      discriminate, at the first visit, between 3 forms of arthritis outcome.
      Validation in other early arthritis clinics is necessary.

PMID- 11840438
TI  - Comparative assessment of leflunomide and methotrexate for the treatment of
      rheumatoid arthritis, by dynamic enhanced magnetic resonance imaging.
AB  - OBJECTIVE: Ethical constraints on the conduct of placebo-controlled trials
      evaluating new therapies for serious chronic diseases, such as rheumatoid
      arthritis (RA), indicate the need for discerning methods to assess treatment
      effect in active-controlled clinical trials. Dynamic gadolinium-enhanced magnetic
      resonance imaging (DEMRI) is a sensitive technique for the detection of synovial
      inflammation in RA. Therefore, this investigation was undertaken to evaluate
      DEMRI as an efficacy assessment tool for differentiating treatment effect in a
      randomized, active-controlled trial comparing leflunomide and methotrexate.
      METHODS: Patients with active RA (n = 39) were randomized in a 2-center,
      prospective, double-blind clinical trial to receive either leflunomide (n = 18)
      or methotrexate (n = 21) therapy for 4 months. DEMRI scans were obtained at
      baseline and at 4 months, and the initial rate of enhancement (IRE) and the
      maximal signal intensity (SI) enhancement (ME) were calculated from the SI
      curves. Clinical improvement was assessed by conventional outcome measures.
      RESULTS: Thirty-four patients (17 treated with leflunomide and 17 with
      methotrexate) had usable baseline and end point DEMRI scans. Leflunomide
      treatment was associated with a significantly greater improvement in IRE compared
      with methotrexate treatment (P < 0.05). Average values of ME indicated reduction
      of inflammation with both leflunomide and methotrexate. The improvement in
      clinical signs and symptoms, as measured by traditional assessments, was
      comparable for both active treatments. CONCLUSION: Results of this study validate
      the sensitivity of DEMRI in detecting inflammatory changes in active RA in
      response to treatment. Improvement in synovial inflammation as measured by IRE
      was significantly better with leflunomide than with methotrexate over 4 months of
      therapy.

PMID- 11840439
TI  - Expression of extracellular matrix metalloproteinase inducer and enhancement of
      the production of matrix metalloproteinases in rheumatoid arthritis.
AB  - OBJECTIVE: To investigate the expression of extracellular matrix
      metalloproteinase inducer (EMMPRIN) at sites of joint destruction in rheumatoid
      arthritis (RA) and to correlate it with the production of matrix
      metalloproteinases (MMPs). METHODS: Reverse transcription-polymerase chain
      reaction was performed to study the existence of EMMPRIN in synovial tissue
      derived from RA and osteoarthritis (OA) patients. In situ hybridization with a
      human complementary DNA specific for EMMPRIN and immunohistochemistry were
      performed to characterize the EMMPRIN-expressing cells at sites of joint
      destruction, including bone. Northern blot analysis was performed to detect the
      level of expression of EMMPRIN messenger RNA (mRNA) in synovial tissue. The
      production of MMP-1 and MMP-3 by synovial tissue from RA patients was examined by
      enzyme-linked immunosorbent assay. RESULTS: Expression of EMMPRIN mRNA was
      detected in synovium from 9 of 11 patients with RA and 1 of 5 patients with OA.
      The presence of mRNA encoding EMMPRIN was recognized in the invasive synovium at
      sites of joint destruction in RA but not OA. Fibroblast-like synovial cells and
      granulocytes were demonstrated to express EMMPRIN mRNA. MMP-1 and MMP-3
      production by synovial tissue was correlated with levels of expression of EMMPRIN
      mRNA, as detected by Northern blotting. CONCLUSION: The expression of EMMPRIN
      stimulates the production of MMP-1 and MMP-3 in the synovial tissue of affected
      joints in RA. The results of this study suggest that EMMPRIN may be one of the
      important factors in progressive joint destruction in RA.

PMID- 11840440
TI  - Involvement of CD4+,CD57+ T cells in the disease activity of rheumatoid
      arthritis.
AB  - OBJECTIVE: To evaluate the relationship between the frequency of peripheral CD57+
      T cells and the physical status of rheumatoid arthritis (RA) patients, and to
      perform cytokine analysis of these CD57+ T cells. METHODS: Four-color
      fluorescence-activated cell sorter analysis was performed to detect both cell
      surface antigens and intracellular cytokines in peripheral blood leukocytes,
      using monoclonal antibodies against CD3, CD4, CD8, CD57, interferon-gamma
      (IFNgamma), and interleukin-4 (IL-4). RA patients were clinically evaluated with
      a modified Health Assessment Questionnaire (M-HAQ), joint score, face scale, and
      visual analog scale (VAS) assessing pain and disease activity. RESULTS: There was
      a significant correlation between the frequency of CD4+,CD57+ T cells and
      erythrocyte sedimentation rate (ESR), whereas a correlation was not found between
      the frequency of CD8+,CD57+ T cells and ESR. The frequency of CD4+,CD57+ T cells
      also showed a significant correlation with the mHAQ score, VAS, and face scale.
      Again, there was no significant correlation between the above-mentioned clinical
      scores and the frequency of CD8+,CD57+ T cells. Flow cytometric analysis of
      intracellular cytokines revealed that 14.5% of the CD57+ T cells produced
      IFNgamma, whereas only 2.8% of the CD57+ T cells produced IL-4 in RA patients.
      CONCLUSION: Evidence showing that the frequency of CD4+,CD57+ T cells among CD3+
      cells of RA patients had a significant correlation not only with ESR but also
      with the physical status of the patients, and that a large proportion of the
      CD4+,CD57+ T cells had the capacity to produce IFNgamma, strongly suggests that
      these CD4+,CD57+ T cells are involved in the immunopathogenesis of RA.

PMID- 11840441
TI  - Magnetic resonance imaging of normal and osteoarthritic trabecular bone structure
      in the human knee.
AB  - OBJECTIVE: To use high-resolution magnetic resonance imaging (MRI) to evaluate
      the trabecular bone structure in the distal femur and the proximal tibia and its
      to correlate the findings with different stages of osteoarthritis (OA) of the
      human knee. METHODS: Axial images of the distal femur and proximal tibia were
      obtained at 1.5 T in patients without and with mild OA and with severe OA. The
      spatial resolution was 195 x 195 microm(2) with a 1-mm slice thickness. Apparent
      measures of trabecular bone volume fraction (BV/TV), trabecular number (Tb.N),
      trabecular separation (Tb.Sp), and trabecular thickness (Tb.Th) were calculated.
      RESULTS: Significant differences existed in the trabecular bone structure of the
      femur and tibia. Differences in trabecular bone structure between the tibia and
      the femur decreased with the degree of OA. The apparent BV/TV, Tb.N, and Tb.Sp in
      the femoral condyles could be used to differentiate healthy patients or patients
      with mild OA from patients with severe OA (P < 0.05). Among individuals, the
      structural variation of the lateral and medial femoral condyle was indicative of
      the extent of the disease. CONCLUSION: High-resolution MRI of the knee joint can
      provide a noninvasive assessment of trabecular bone structure. Trabecular bone
      structure, determined by high-resolution MRI, shows significant variation in
      patients with varying degrees of OA. The impact of OA on trabecular bone is
      different in the tibia than in the femur, and this difference depends on the
      extent of the disease.

PMID- 11840442
TI  - Nitric oxide-mediated chondrocyte cell death requires the generation of
      additional reactive oxygen species.
AB  - OBJECTIVE: Chondrocyte cell death, possibly related to increased production of
      endogenous nitric oxide (NO), has been observed during the pathogenesis of
      osteoarthritis and rheumatoid arthritis. The purpose of this study was to
      investigate the potential role of NO in causing chondrocyte cell death and to
      determine the contribution of other reactive oxygen species (ROS). METHODS: Cell
      death and cytotoxicity were evaluated in human articular chondrocytes in response
      to various NO donor compounds with and without agents that stimulate or inhibit
      the production of additional ROS using both the alginate bead and the monolayer
      culture systems. Cell death was quantified by a total cell count with fluorescent
      labels, and cytotoxicity was measured as a function of cellular NADH- and NADPH
      dependent dehydrogenase activity. To determine if the redox status of the
      chondrocyte could influence the observed effect of NO, cells were preincubated
      for 24 hours in L-cystine- and glutathione (GSH)-depleted media to reduce
      intracellular GSH levels, a major defense mechanism against oxidative stress.
      Apoptosis was analyzed with the quantification of histone-associated DNA
      fragments. RESULTS: Treatment of chondrocytes with peroxynitrite (ONOO-), 3
      morpholinosydnonimine (SIN-1), and sodium nitroprusside (SNP) resulted in
      apoptotic cell death at concentrations of 0.5 mM, 1.0 mM, and 0.5 mM,
      respectively. In contrast, treatment of chondrocytes with diazeniumdiolates (or
      the "NOC" compounds, NOC-5 and NOC-12) at concentrations as high as 2.0 mM did
      not cause cell death. Furthermore, NOC-5 and NOC-12, at all concentrations tested
      (0.125-2.0 mM), could prevent cell death caused by oxidative stress. Selective
      ROS scavengers protected against cell death caused by either SIN-1 or ONOO-;
      however, no protection could be afforded against the cytotoxicity of SNP with any
      of the ROS scavengers tested. CONCLUSION: These results show that NO by itself is
      not cytotoxic to cultured chondrocytes and can even be protective under certain
      conditions of oxidative stress. Chondrocyte cell death from NO occurs under
      conditions where other ROS are also generated.

PMID- 11840443
TI  - Assessment of the gene expression profile of differentiated and dedifferentiated
      human fetal chondrocytes by microarray analysis.
AB  - OBJECTIVE: To study the changes in patterns of gene expression exhibited by human
      chondrocytes as they dedifferentiate into fibroblastic cells in culture in order
      to better understand the mechanisms that control this process and its
      relationship to the phenotypic changes that occur in chondrocytes during the
      development of osteoarthritis (OA). METHODS: Human fetal epiphyseal chondrocytes
      (HFCs) were cultured either on poly-(2-hydroxyethyl methacrylate)-coated plates
      (differentiated HFC cultures) or in plastic tissue culture flasks as monolayers
      (dedifferentiated HFC cultures). Following 11 days of culture under either
      condition, poly(A+) RNA was isolated from the two cell populations and subjected
      to a gene expression analysis using a microarray containing approximately 5,000
      known human genes and approximately 3,000 expressed sequence tags (ESTs).
      RESULTS: A > or =2-fold difference in the expression of 62 known genes and 6 ESTs
      was observed between the two cell types. The differences in expression of several
      of the genes detected by the microarray hybridization were confirmed by Northern
      analyses. Two transcription factor genes, TWIST and HIF-1alpha, and a cellular
      adhesion protein gene, cadherin 11, were markedly regulated in response to
      differentiation and dedifferentiation. Expression of these genes was also
      detected in adult normal and OA cartilage and chondrocytes. Analysis of the gene
      expression profile of HFCs revealed a complex pattern of gene expression,
      including many genes not yet reported to be expressed by chondrocytes.
      CONCLUSION: Chondrocytes in monolayer become dedifferentiated, acquiring a
      fibroblast-like appearance and changing their pattern of gene expression from one
      of expression of chondrocyte-specific genes to one that resembles a fibroblastic
      or chondroprogenitor-like pattern. Changes in gene expression associated with the
      process of dedifferentiation of HFCs in vitro were observed in a wide variety of
      genes, including genes encoding extracellular matrix proteins, transcription
      factors, and growth factors. At least 3 of the genes that were regulated in
      response to dedifferentiation were also found to be expressed in adult normal and
      OA articular cartilage and chondrocytes.

PMID- 11840444
TI  - Urea as a passive transport marker for arthritis biomarker studies.
AB  - OBJECTIVE: To develop a method to correct for the unknown dilution of synovial
      fluid that occurs during lavage of a joint, we evaluated the utility of urea, a
      molecule that is neither synthesized nor metabolized by joint tissues, as a means
      of correcting for the dilutional effects of lavage procedures and effusions.
      METHODS: Joint fluids were obtained from normal canine joints by direct
      aspiration (n = 41) and lavage (n = 10). Acute joint injury was induced in 4
      joints by intraarticular injection of chymopapain. Serum and joint fluid levels
      of urea and joint fluid concentrations of glucose, lactate, cartilage oligomeric
      matrix protein (COMP), and keratan sulfate (KS) were measured in these 55 joints.
      RESULTS: Urea concentrations in joint fluid were directly proportional to those
      in serum throughout a wide range of concentrations in normal joints. From this
      relationship, the dilution factor introduced by joint lavage was determined. This
      method was applied to quantify biomarker concentrations in synovial lavage fluid
      and was found to successfully correct for lavage-induced dilution of glucose,
      lactate, COMP, and KS to levels equivalent to those in samples aspirated
      directly. In the context of chymopapain-induced joint effusion, urea
      concentrations continued to be proportional to serum concentrations, but were
      much lower, enabling an estimation of the change in the volume of distribution
      (V(d)) of a marker due to a change in joint water content in the setting of
      inflammation characterized by effusion. Lactate and KS levels rose markedly in
      response to chymopapain. After adjustment for the V(d), the glucose concentration
      in the chymopapain-injected joints did not change. CONCLUSION: Urea provides a
      robust method of quantifying and correcting for the dilution of synovial fluid
      due to joint lavage or inflammation. This method is potentially applicable to
      surrogate marker studies in human arthritis.

PMID- 11840445
TI  - Increased prevalence of renal disease in systemic lupus erythematosus families
      with affected male relatives.
AB  - OBJECTIVE: To distinguish familial differences from sex-related differences in
      the clinical manifestations of systemic lupus erythematosus (SLE). METHODS: A
      total of 372 affected individuals from 160 multiplex SLE pedigrees were analyzed.
      Twenty-five of these pedigrees contained at least 1 affected male relative.
      Comparisons of the presence of each of the 11 1982 American College of
      Rheumatology criteria for SLE were made between female family members with
      affected male relatives and those without affected male relatives, using Fisher's
      exact tests. RESULTS: The presence of renal disease was significantly increased
      in female family members with an affected male relative when compared with those
      with no affected male relative (68% and 43%, respectively; P = 0.002). This trend
      remained after stratifying by race and was most pronounced in European Americans.
      A familial basis for differences in hematologic and immunologic manifestations
      was also suggested, while arthritis and dermatologic features appeared to be most
      influenced by sex. CONCLUSION: Our results demonstrate that the increased
      prevalence of renal disease previously reported in men with SLE is, in large
      part, a familial rather than sex-based difference, at least in multiplex SLE
      families. Distinguishing familial from sex-related differences may facilitate
      efforts to understand the genetic and hormonal factors that underlie this complex
      autoimmune disease.

PMID- 11840446
TI  - Risk factors for damage in childhood-onset systemic lupus erythematosus:
      cumulative disease activity and medication use predict disease damage.
AB  - OBJECTIVE: The Systemic Lupus International Collaborating Clinics/American
      College of Rheumatology (SLICC/ACR) Damage Index measures damage in adult
      patients with systemic lupus erythematosus (SLE), but its usefulness in patients
      with childhood-onset SLE has not been examined. This study was conducted to
      evaluate the sensibility of the SLICC/ACR Damage Index, to investigate how
      cumulative disease activity is related to damage in childhood-onset SLE, and to
      identify other risk factors for damage in childhood-onset SLE. METHODS: Disease
      activity and damage in 66 patients with newly diagnosed childhood-onset SLE were
      assessed retrospectively, and information on potential risk factors for damage
      (age, race, sex, medications, duration of disease, hypertension, body mass index,
      antiphospholipid antibodies, kidney disease, acute thrombocytopenia) was
      obtained. In addition, a group of physicians was surveyed to establish the
      sensibility of the SLICC/ACR Damage Index in childhood-onset SLE. RESULTS: The
      SLICC/ACR Damage Index was found to have face, content, and construct validity
      when used in children. The mean SLICC/ACR Damage Index score of the patients was
      1.76 (mean followup 3.3 years). Cumulative disease activity over time was the
      single best predictor of damage (R(2) = 0.30). Other, possibly important risk
      factors for damage were corticosteroid treatment, the presence of
      antiphospholipid antibodies, and acute thrombocytopenia. It was determined that
      immunosuppressive agents may be protective. CONCLUSION: The SLICC/ACR Damage
      Index, though useful in childhood-onset SLE, may benefit from the introduction of
      weightings and redefinition of some of the items. Ongoing disease activity leads
      to disease damage, and treatment should be prompt. Prolonged use of high-dose
      corticosteroids may further increase damage, but use of immunosuppressive agents
      may protect against disease damage; this latter finding may have potential
      implications for the treatment of childhood-onset SLE and deserves further study.
      The relationship between disease activity and concomitant use of medication also
      requires further investigation.

PMID- 11840447
TI  - Th2-oriented profile of male offspring T cells present in women with systemic
      sclerosis and reactive with maternal major histocompatibility complex antigens.
AB  - OBJECTIVE: To characterize the cytokine production profile of male-offspring T
      cells reactive against maternal major histocompatibility complex (MHC) antigens
      present in the peripheral blood and/or skin from women with systemic sclerosis
      (SSc). METHODS: T cell clones were generated from peripheral blood and/or skin
      biopsy specimens from 3 women with SSc of recent onset and from peripheral blood
      from 3 healthy women, all of whom had 1 male child. All clones were screened for
      their proliferative response in vitro to maternal MHC antigens by measuring (3)H
      thymidine uptake and for their expression of Y chromosome by using fluorescence
      in situ hybridization. The concentrations of interferon-gamma and interleukin-4
      (IL-4) released by T cell clones in response to maternal MHC antigens were
      evaluated in culture supernatants, using appropriate enzyme-linked immunosorbent
      assays. RESULTS: Thirty-nine of 202 T cell clones generated from women with SSc
      and 11 of 312 from healthy women proliferated in vitro in response to maternal
      MHC antigens. Seven MHC-reactive T cell clones obtained from women with SSc and 1
      obtained from healthy women exhibited the Y chromosome, thus indicating that the
      clones were derived from T cells of male offspring. All clones generated from
      male-offspring T cells of SSc women (but not from those of healthy women)
      produced significantly higher levels of IL-4 in response to stimulation with
      maternal MHC antigens than did all other clones generated from the same women.
      The other clones proliferated in response to maternal or allogeneic MHC antigens
      but did not exhibit the Y chromosome. CONCLUSION: Male-offspring T cells that are
      present in the blood and skin of women with SSc and react with maternal MHC
      antigens exhibit a Th2-oriented profile, supporting the possibility that a
      chronic graft-versus-host reaction attributable to long-term microchimerism plays
      a pathogenic role in SSc.

PMID- 11840448
TI  - Reproductive factors and the risk of scleroderma: an Italian case-control study.
AB  - OBJECTIVE: To investigate the association between scleroderma (systemic
      sclerosis; SSc) and reproductive factors in a hospital-based case-control study
      conducted at the University Hospital of Verona in Northeastern Italy. METHODS:
      Forty-six confirmed cases of SSc in women (42 with diffuse SSc and 4 with limited
      SSc) and 153 female control subjects with orthopedic disorders were recruited at
      the University Hospital. For each subject, information on age at first pregnancy,
      number of children and abortions, and use of oral contraceptives was obtained by
      means of a structured questionnaire, and information on the subject's
      occupational history and lifestyle factors was also sought. RESULTS: Parous women
      had a reduced risk of SSc (age-adjusted odds ratio [OR] 0.3, 95% confidence
      interval [95% CI] 0.1-0.8) compared with nulliparous women. The risk decreased
      with an increasing number of children: the age-adjusted OR was 0.6 (95% CI 0.2
      1.7) for those women who had had 1 child, 0.3 (95% CI 0.1-0.7) for those having
      had 2 children, and 0.3 (95% CI 0.1-0.8) for those having had 3 or more children.
      Abortive pregnancies were inversely related to SSc risk: for women who had an
      abortion, the OR was 0.5 (95% CI 0.2-1.5) compared with women with no history of
      abortion. The overall history of any pregnancy (abortive or age-adjusted
      complete) was associated with a reduced risk of SSc (age-adjusted OR 0.3, 95% CI
      0.1-0.7). CONCLUSION: Since the incidence of SSc is higher in women and has its
      peak after childbearing age, it has been hypothesized that immunobiologic
      modifications during pregnancy may be associated with SSc development. Our
      findings showing a reduced risk of SSc among parous women seem to exclude the
      possibility of pregnancy itself as a risk factor for SSc. The role of HLA
      compatibility between the mother and the fetus, however, should be evaluated in
      further research.

PMID- 11840449
TI  - Therapeutic effects of acetylsalicylic acid in giant cell arteritis.
AB  - OBJECTIVE: In giant cell arteritis (GCA), inflammatory lesions typically produce
      interferon-gamma(IFNgamma)-- and nuclear factor kappaB (NF-kappaB)-dependent
      monokines. Corticosteroids influence disease activity by repressing NF-kappaB
      dependent genes but have only marginal effects on IFNgamma. The current study
      explored whether acetylsalicylic acid (ASA) had cytokine-repressing activity in
      GCA and could function as a steroid-sparing agent. METHODS: Temporal artery
      severe combined immunodeficiency (SCID) mouse chimeras were created by engrafting
      inflamed temporal arteries into SCID mice. Chimeras were treated with ASA,
      indomethacin, or dexamethasone for 3 weeks. Temporal artery grafts were harvested
      and cytokine message was semiquantified by polymerase chain reaction-enzyme
      linked immunosorbent assay. The ability of dexamethasone and ASA to suppress
      IFNgamma and interleukin-1beta (IL-1beta) messenger RNA and protein production
      was also tested in vitro using T cell clones and monocytes derived from patients
      with GCA. Drug-induced effects on the transcription factors NF-kappaB and
      activator protein 1 (AP-1) were assessed by electrophoretic mobility shift assays
      (EMSAs). RESULTS: At clinically relevant doses, 20-100 mg/kg, ASA was a highly
      effective inhibitor of cytokine transcription in temporal arteries. While
      dexamethasone preferentially targeted NF-kappaB-regulated monokines, ASA acted
      predominantly by suppressing IFNgamma. Indomethacin failed to reduce tissue
      IFNgamma transcription, which therefore excluded the inhibition of
      cyclooxygenases as a critical mechanism. IFNgamma production by T cell clones was
      highly sensitive to ASA-mediated suppression, whereas IL-1beta production by
      lipopolysaccharide-stimulated monocytes responded primarily to dexamethasone. The
      combination of ASA and dexamethasone had synergistic effects. EMSAs demonstrated
      that ASA interfered with the formation of AP-1, whereas dexamethasone suppressed
      the nuclear translocation of NF-kappaB. CONCLUSION: The results of this study
      provide evidence of the complementary action of ASA and corticosteroids in
      suppressing proinflammatory cytokines in the vascular lesions of GCA.

PMID- 11840450
TI  - Results and long-term followup of intravenous immunoglobulin infusions in
      chronic, refractory polymyositis: an open study with thirty-five adult patients.
AB  - OBJECTIVE: Polymyositis is a rare inflammatory muscular disease of unknown cause.
      Corticosteroids and immunosuppressive drugs are the first choice of therapy but
      are not always effective and may cause serious side effects. Many studies have
      shown that polyvalent intravenous immunoglobulin (IVIG) may be of interest for
      the treatment of dermatomyositis. We carried out an open, prospective study to
      evaluate the efficacy of IVIG in subjects with polymyositis that was refractory
      to traditional treatments, and we evaluated the benefits of this therapy over a
      long-term period of followup. METHODS: Thirty-five adult white patients (20
      female, 15 male, mean age 43.5 years [SD 16.8]) with chronic, refractory
      polymyositis were treated with high doses of IVIG, after the patients had
      received the following traditional treatments: prednisone (n = 35), methotrexate
      (n = 24), azathioprine (n = 13), cyclophosphamide (n = 4), cyclosporine (n = 7),
      chlorambucil (n = 1), plasmapheresis (n = 8), lymphopheresis (n = 1), and total
      body irradiation (n = 1). There had been no changes in the patients' treatment in
      the 2 months before the initiation of IVIG therapy, and doses were not increased
      during IVIG treatment. We used preparations of polyvalent human IVIG with
      increased concentrations of intact IgG. The patients received 1 gm/kg/day for 2
      consecutive days per month. The mean course of treatment was 4-6 months. The
      clinical assessment involved the evaluation of proximal muscle power, muscle
      disability scale score, and esophageal disorders. The biochemical evaluations
      carried out before each treatment period were compared by Student's t-test and
      nonparametric Wilcoxon test. Results were considered to be significant at P =
      0.05. RESULTS: In the short-term, significant clinical improvement was noted in
      25 of the 35 patients (71.4%). Mean muscle power was estimated before and after
      IVIG therapy and was found to be significantly improved (P < 0.01). All patients
      had a significant biochemical response. Mean creatine kinase levels during IVIG
      therapy decreased significantly before the fourth IVIG perfusion (P < 0.01). Side
      effects, usually minor, were noted in 6 patients. This benefit allowed the
      initial prednisone dose to be reduced by >50% in all patients. The mean (+/- SD)
      followup time for the 25 patients who responded favorably to IVIG treatment was
      51.4 +/- 13.1 months. Twelve of these 25 patients remained in full remission
      following their initial course of IVIG, resulting in complete stoppage of
      medication in 5 patients or low doses of steroids in 7 patients. The condition of
      6 patients remained improved and no other drugs were prescribed, but the patients
      remained dependent on IVIG infusions. Seven of the 25 patients who responded well
      to IVIG treatment relapsed at an average of 17.1 months (range 4-23 months) after
      the discontinuation of IVIG. CONCLUSION: IVIG is an interesting therapy for the
      treatment of polymyositis, with results showing that the condition of
      approximately 70% of the patients tested improved. After the discontinuation of
      the IVIG therapy, the efficacy remained stable in 50% of the patients, with a
      followup of over 3 years.

PMID- 11840451
TI  - Magnesium abnormalities of skeletal muscle in dermatomyositis and juvenile
      dermatomyositis.
AB  - OBJECTIVE: To characterize abnormalities in magnesium levels in the muscles of
      patients with dermatomyositis (DM) and juvenile dermatomyositis (JDM) and to
      evaluate the beneficial effects of prednisone and immunosuppressive therapy in
      elevating free magnesium (Mg(2+)) and ATP-bound magnesium (Mg-ATP). METHODS: The
      study groups consisted of 12 adult patients with DM and 10 juvenile patients with
      JDM. The 2 control groups were 11 normal adults and 6 healthy children. Levels of
      total ATP in the quadriceps muscles of the subjects were determined during rest,
      exercise, and recovery, using noninvasive P-31 magnetic resonance spectroscopy
      (MRS). Concentrations of the biologically active free Mg(2+) and the
      enzymatically active Mg-ATP complex were determined from the spectroscopy data by
      calculation of the chemical shifts of the beta-phosphate peak of ATP. RESULTS: Mg
      ATP levels in DM and JDM myopathic muscles were at least 37% lower than those in
      normal muscles during rest, exercise, and recovery from exercise (P < 0.0005).
      Free Mg(2+) levels were normal in DM and JDM myopathic muscles at rest, but were
      significantly lower than control values during exercise and recovery (P < 0.029
      and P < 0.005 for DM and JDM, respectively). Prednisone and immunosuppressive
      therapy partially reversed the magnesium abnormalities, as evidenced by elevation
      of the levels of Mg-ATP and free Mg(2+). CONCLUSION: Low levels of Mg-ATP and
      free Mg(2+) are concordant with weakness and fatigue observed in DM and JDM
      patients. Immunosuppressive therapy alleviates, in part, the magnesium deficits
      in the diseased muscles. Therefore, Mg-ATP and free Mg(2+) may play a significant
      role in the pathophysiology of these diseases.

PMID- 11840452
TI  - The role of biomechanical factors and HLA-B27 in magnetic resonance imaging
      determined bone changes in plantar fascia enthesopathy.
AB  - OBJECTIVE: To study the role of biomechanical factors and HLA-B27 in plantar
      fasciitis. METHODS: T1-weighted and T2 spectral presaturation with inversion
      recovery (fat suppressed) magnetic resonance imaging (MRI) sequences of the
      plantar fascia insertion and adjacent bone were performed on 28 patients with
      plantar fasciitis; 17 had spondylarthropathy (SpA)-associated disease, and 11 had
      mechanically induced disease. The relationship between the degree of bone edema,
      scored on a semiquantitative scale (from absent to severe), and the patient's HLA
      B27 status was determined. RESULTS: On MRI, edema within the soft tissue at the
      enthesis was evident in both groups. Bone edema in the adjacent calcaneum was
      evident in 64.7% (11 of 17) of patients with SpA and in 45% (5 of 11) of those
      with mechanically induced disease (P = 0.441). HLA-B27 was identified in 9 (53%)
      of the patients with SpA but in none (0%) of those with mechanically induced
      disease. All 6 of the SpA patients with extensive bone edema but none of the 5
      SpA patients with mild bone edema were HLA-B27 positive (P = 0.002). CONCLUSION:
      The association of HLA-B27 with bone pathology in early enthesitis may have
      implications for a better understanding of the pathogenesis of SpA.

PMID- 11840453
TI  - Nimesulide, a preferential cyclooxygenase 2 inhibitor, suppresses peroxisome
      proliferator-activated receptor induction of cyclooxygenase 2 gene expression in
      human synovial fibroblasts: evidence for receptor antagonism.
AB  - OBJECTIVE: To characterize the inhibitory effects of therapeutic concentrations
      of the nonsteroidal antiinflammatory drug nimesulide (NIM) on peroxisome
      proliferator-activated receptor (PPAR)-induced cyclooxygenase 2 (COX-2) gene
      expression in human synovial fibroblasts (HSFs) from patients with osteoarthritis
      (OA) and to define the intracellular mechanisms mediating the response. METHODS:
      PPARalpha and PPARgamma messenger RNA (mRNA) expression and protein synthesis in
      OA HSFs were measured by reverse transcription-polymerase chain reaction and
      electrophoretic mobility shift assay, respectively. Experiments investigating
      endogenous and overexpressed PPARalpha and PPARgamma activation of COX-2 mRNA and
      protein were conducted by incubating nontransfected and transfected cells with
      increasing concentrations of cognate ligands WY-14,643 (alpha agonist),
      ciglitasone (gamma agonist), and 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d
      PGJ(2)) in the absence or presence of NIM and NS-398 (1 microM). COX-2 mRNA and
      protein were measured by Northern and Western blotting procedures, respectively.
      Receptor activation studies were evaluated by cotransfecting pSG5-Gal 4 DNA
      binding domain (DBD)-PPARalpha ligand binding domain (LBD) or pSG5-Gal 4 DBD
      PPARgamma LBD chimeric constructs with a 5x Gal 4 enhancer site tk-tataa
      luciferase reporter under ligand stimulation in the presence or absence of
      increasing concentrations of NIM. Gene transactivation analyses were conducted by
      treating cells overexpressing cytomegalovirus (CMV)-PPARalpha or CMV-PPARgamma
      expression constructs with either a PPAR response element (PPRE)-luciferase
      construct containing 3 DR1 acyl-coenzyme A (acyl-CoA) oxidase gene response
      elements or human COX-2 promoter constructs with WY-14,643, ciglitasone, and 15d
      PGJ(2) in the presence or absence of increasing concentrations of NIM. RESULTS:
      Human synovial cells expressed functional PPAR isoforms, PPARalpha and PPARgamma.
      Neither receptor agonists nor antagonists modulated the intracellular protein
      levels of PPAR. PPARalpha and, especially, PPARgamma mediated the induction of
      COX-2 gene expression by receptor agonists. Stimulation of COX-2 mRNA expression
      and protein synthesis by 15d-PGJ(2) appeared to occur through a receptor
      independent process. NIM inhibited PPAR agonist stimulation of COX-2 expression
      and synthesis in a dose-dependent manner in both nontransfected cells and cells
      overexpressing both receptor isoforms. NIM potently abrogated basal and ligand
      stimulated PPRE(3X) DR1 acyl-CoA oxidase-driven luciferase activity and also
      human PPRE-containing COX-2 promoter activity. CONCLUSION: PPAR-mediated
      induction of COX-2 expression and synthesis in human OA synovial fibroblasts is
      inhibited by therapeutic concentrations of NIM through the functional antagonism
      of ligand-dependent receptor activation, with the resultant suppression of PPAR
      dependent transactivation of target genes (e.g., COX-2).

PMID- 11840454
TI  - Inflammation is preceded by tumor necrosis factor-dependent infiltration of
      mesenchymal cells in experimental arthritis.
AB  - OBJECTIVE: To determine the involvement of mesenchymal progenitor cells in the
      induction of collagen-induced arthritis (CIA). METHODS: DBA/1 mice were immunized
      with type II collagen in adjuvant or adjuvant alone, and the presence of
      mesenchymal cells in the joints of prearthritic mice was studied by
      immunohistochemistry. RESULTS: An analysis of the joints on day 10
      postimmunization (at least 10 days before the onset of arthritis) revealed
      synovial hyperplasia without leukocytic infiltration. Large, round cells
      expressing bone morphogenetic protein receptors (BMPRs), which serve as markers
      for primitive mesenchymal cells, were present in increased numbers in the bone
      marrow adjacent to the joint, in the synovium itself, and within enlarged bone
      canals that connect the bone marrow to the synovium. Similar changes were
      observed in mice given adjuvant without collagen. Adjuvant-induced infiltration
      of BMPR(+) cells and enlargement of bone canals were abrogated by anti-tumor
      necrosis factor (anti-TNF) treatment and were absent in TNFR p55/p75(-/-) mice.
      Increased numbers of bone marrow cells and enlarged bone canals were observed in
      nonimmunized TNF transgenic mice (which spontaneously develop arthritis).
      CONCLUSION: These findings suggest that in CIA, there is an antigen-independent
      (innate) prearthritic phase that prepares the joint for the subsequent immune
      mediated arthritis. The induction phase involves marrow-derived mesenchymal cells
      and requires the presence of TNF.

PMID- 11840455
TI  - Constitutive expression of BCL-X(L) in the T lineage attenuates collagen-induced
      arthritis in Bcl-X(L) transgenic mice.
AB  - OBJECTIVE: To determine if inhibition of T cell apoptosis through constitutive
      expression of Bcl-X(L) in the T lineage influences inflammatory arthritis in the
      mouse collagen-induced arthritis (CIA) model. METHODS: The incidence and severity
      of arthritis were quantified in Bcl-X(L) transgenic mice and nontransgenic
      littermates after immunization with type II collagen (CII). To correlate T cell
      responses with disease phenotype, antigen-specific T cell proliferation was
      measured by (3)H-thymidine incorporation. Apoptosis and cell cycle progression
      were analyzed by flow cytometry using propidium iodide. Production of CII
      specific interferon-gamma (IFNgamma), interleukin-5 (IL-5), and IL-10 was
      determined by enzyme-linked immunosorbent assay. RESULTS: Disease severity in CIA
      was significantly attenuated in Bcl-X(L) transgenic mice compared with their
      nontransgenic littermates. Inhibition of CIA was associated with decreased T cell
      apoptosis, delayed cell cycle progression, and reduced IFNgamma production.
      CONCLUSION: Rather than promoting inflammation, inhibition of apoptosis by
      expression of the Bcl-X(L) protein in the T lineage attenuates disease
      progression in CIA, probably through inhibition of IFNgamma production.

PMID- 11840456
TI  - Vitamin E uncouples joint destruction and clinical inflammation in a transgenic
      mouse model of rheumatoid arthritis.
AB  - OBJECTIVE: Reactive oxygen species are thought to play a role in rheumatoid
      arthritis (RA) in humans. We postulated that antioxidant treatment could have a
      beneficial effect in this disease. We therefore investigated the effects of
      vitamin E in the transgenic KRN/NOD mouse model of RA. METHODS: Mice were treated
      by gavage with oral vitamin E (alpha-tocopherol). Clinical, histologic, and
      biochemical parameters were assessed for 6 weeks. RESULTS: Vitamin E treatment
      did not modify the clinical features of the disease (date of onset or disease
      intensity, as measured by the articular index), but it did prevent joint
      destruction, as measured by qualitative and semiquantitative analyses. Redox
      status did not differ between treated and control mice. White blood cell
      chemiluminescence was higher in transgenic KRN/NOD mice than in controls, but
      vitamin E treatment attenuated this difference. Vitamin E treatment of the
      transgenic animals led to a significant decrease in the levels of interleukin-(IL
      1beta) but not tumor necrosis factor alpha. CONCLUSION: Vitamin E seems to
      uncouple joint inflammation and joint destruction in this model of RA, with a
      beneficial effect on joint destruction. Since many investigations are currently
      in progress to evaluate the benefit of interventions targeted toward anti-IL
      1beta, our findings suggest opportunities of therapeutic interest in human RA.

PMID- 11840457
TI  - Suppression of autoimmune arthritis in interleukin-1-deficient mice in which T
      cell activation is impaired due to low levels of CD40 ligand and OX40 expression
      on T cells.
AB  - OBJECTIVE: To elucidate the roles of interleukin-1 (IL-1) in the development of 2
      etiologically different rheumatoid arthritis (RA) models: the type II collagen
      (CII)-induced arthritis (CIA) model and the human T cell leukemia virus type I
      transgenic (HTLV-I Tg) mouse model. METHODS: For the CIA model, DBA/1J-background
      IL-1alpha-/-, IL-1beta-/-, IL-1alpha/beta-/-, and wild-type littermate mice were
      immunized with CII. For the HTLV-I Tg model, BALB/c IL-1beta-/- or IL-1alpha/beta
      /- mice were crossed with HTLV-I Tg mice. The effects of IL-1 deficiency were
      assessed as follows: Development of arthritis was assessed both macroscopically
      and microscopically. Serum antibody titer was measured by enzyme-linked
      immunosorbent assay. Proliferative response of lymph node cells was assayed by
      measurement of (3)H-thymidine incorporation. Expression of T cell surface
      molecule CD40 ligand (CD40L) and OX40 was determined by multicolor flow
      cytometric analysis. RESULTS: The development of arthritis was markedly
      suppressed in IL-1alpha/beta-/- mice in both models, although the effect was less
      prominent in HTLV-I Tg mice. Deficiency of only IL-1alpha or only IL-1beta was
      also associated with disease suppression. Antibody production after immunization
      with CII was normal in IL-1alpha/beta-/- mice, while autoantibody production was
      suppressed in IL-1alpha/beta-/- HTLV-I Tg mice. In IL-1alpha/beta-/- mice, the T
      cell proliferative response against CII was greatly reduced in both the CIA and
      the HTLV-I Tg models, suggesting inefficiency of T cell activation. Furthermore,
      expression of CD40L and OX40 on T cells was greatly reduced in IL-1alpha/beta-/-
      mice. CONCLUSION: These observations suggest that T cell activation by IL-1 is
      important for the development of autoimmunity and arthritis in these mice.

PMID- 11840458
TI  - Antiphospholipid antibodies induced in mice by immunization with a
      cytomegalovirus-derived peptide cause thrombosis and activation of endothelial
      cells in vivo.
AB  - OBJECTIVE: To characterize the binding and functional properties of
      antiphospholipid antibodies (aPL) induced by immunization with a viral peptide
      and to determine whether aPL are pathogenic in vivo. METHODS: Ten murine
      monoclonal aPL were generated from spleen cells of PL/J mice immunized with TIFI,
      a phospholipid-binding peptide spanning Thr(101)-Thr(120) of ULB0-HCMVA from
      human cytomegalovirus (CMV), which shares structural similarity with the
      phospholipid-binding site of beta(2)-glycoprotein I (beta(2)GPI). RESULTS: The
      antibodies generated had aPL activity that was inhibited by cardiolipin
      liposomes, and this inhibition was enhanced in the presence of beta(2)GPI. Some
      of the antibodies exhibited binding to cultured endothelial cells in vitro, and
      some had lupus anticoagulant activity. Injection with 2 of the monoclonal aPL in
      mice resulted in a significant increase in the number of leukocytes adhering to
      endothelial cells and enhanced thrombus formation in vivo. CONCLUSION: These
      results indicate that aPL induced by immunization with a phospholipid-binding CMV
      peptide are pathogenic in vivo. The results also suggest a mechanism (molecular
      mimicry) by which pathogenic aPL may be generated in patients with
      antiphospholipid syndrome.

PMID- 11840459
TI  - The HLA-B*2709 subtype confers susceptibility to spondylarthropathy.

PMID- 11840460
TI  - Variant mannose-binding lectin genotypes and outcome in early versus late
      rheumatoid arthritis: comment on the article by Ip et al.

PMID- 11840462
TI  - Association of Fcgamma receptor IIIA polymorphism with rheumatoid arthritis:
      comment on the article by Morgan et al.

PMID- 11840464
TI  - Effect of etanercept on tenosynovitis and nodules in rheumatoid arthritis.

PMID- 11840465
TI  - How frequently and how soon should we screen our patients for the presence of
      antimalarial retinopathy?

PMID- 11840466
TI  - Distinguishing congenital from acquired heart block: comment on the article by
      Julkunen and Eronen.

PMID- 11840468
TI  - The difficulties in establishing a birth order or maternal age effect in
      ankylosing spondylitis: comment on the article by Baudoin et al.

PMID- 11840470
TI  - Somatization does not fit all fibromyalgia patients: comment on the article by
      Winfield.

PMID- 11840471
TI  - Gouty tophi in a pancreatic pseudocyst.

PMID- 11840472
TI  - Clinical images: Unrecognized SAPHO syndrome as a rare cause of chronic anterior
      chest.

PMID- 11840474
TI  - Vesicular glutamate transporter DNPI/VGLUT2 mRNA is present in C1 and several
      other groups of brainstem catecholaminergic neurons.
AB  - The mouse glutamate vesicular transporter VGLUT2 has recently been characterized.
      The rat homolog of VGLUT2, differentiation-associated Na(+)/P(i) cotransporter
      (DNPI), was examined using a digoxigenin-labeled DNPI/VGLUT2 cRNA probe in the
      present study to determine which, if any, of the various groups of pontine or
      medullary monoaminergic neurons express DNPI/VGLUT2 mRNA and, thus, are
      potentially glutamatergic. DNPI/VGLUT2 mRNA was widely distributed within the
      brainstem and seemed exclusively neuronal. By using a double in situ
      hybridization method, the presence of the mRNA for DNPI/VGLUT2 and glutamic acid
      decarboxylase (GAD)-67 was mutually exclusive. By combining DNPI/VGLUT2 mRNA
      detection and conventional immunohistochemistry, DNPI/VGLUT2 mRNA was
      undetectable in lower brainstem cholinergic and serotonergic cells, but it was
      present in several tyrosine hydroxylase-immunoreactive (TH-ir) cell groups.
      DNPI/VGLUT2 mRNA was detected in most of the adrenergic neurons of the C1, C2,
      and C3 groups (75-80% of TH-ir neurons), in the A2 noradrenergic group (80%), and
      in vast numbers of area postrema cells. Within the A1 region, many fewer TH-ir
      cells contained DNPI/VGLUT2 (16%). Finally, DNPI/VGLUT2 mRNA was undetectable in
      the pontine noradrenergic cell groups (A5 and A6/locus coeruleus). In conclusion,
      the general pattern of DNPI/VGLUT2 expression and its exclusion from GABAergic,
      cholinergic, and serotonergic neurons supports the notion that DNPI/VGLUT2 mRNA
      identifies a subset of glutamatergic neurons in the lower brainstem. Within this
      region several catecholaminergic cell groups appear to be glutamatergic,
      including but not limited to the adrenergic cell groups C1-C3. Based on the
      present evidence, the noradrenergic cell groups of the pons (A5 and A6) do not
      contain either known vesicular glutamate transporter and are most likely not
      glutamatergic.

PMID- 11840475
TI  - Vesicular glutamate transporter DNPI/VGLUT2 is expressed by both C1 adrenergic
      and nonaminergic presympathetic vasomotor neurons of the rat medulla.
AB  - The main source of excitatory drive to the sympathetic preganglionic neurons that
      control blood pressure is from neurons located in the rostral ventrolateral
      medulla (RVLM). This monosynaptic input includes adrenergic (C1), peptidergic,
      and noncatecholaminergic neurons. Some of the cells in this pathway are suspected
      to be glutamatergic, but conclusive evidence is lacking. In the present study we
      sought to determine whether these presympathetic neurons express the vesicular
      glutamate transporter BNPI/VGLUT1 or the closely related gene DNPI, the rat
      homolog of the mouse vesicular glutamate transporter VGLUT2. Both BNPI/VGLUT1 and
      DNPI/VGLUT2 mRNAs were detected in the medulla oblongata by in situ
      hybridization, but only DNPI/VGLUT2 mRNA was present in the RVLM. Moreover, BNPI
      immunoreactivity was absent from the thoracic spinal cord lateral horn.
      DNPI/VGLUT2 mRNA was present in many medullary cells retrogradely labeled with
      Fluoro-Gold from the spinal cord (T2; four rats). Within the RVLM, 79% of the
      bulbospinal C1 cells contained DNPI/VGLUT2 mRNA. Bulbospinal noradrenergic A5
      neurons did not contain DNPI/VGLUT2 mRNA. The RVLM of six unanesthetized rats
      subjected to 2 hours of hydralazine-induced hypotension contained tenfold more c
      Fos-ir DNPI/VGLUT2 neurons than that of six saline-treated controls. c-Fos-ir
      DNPI/VGLUT2 neurons included C1 and non-C1 neurons (3:2 ratio). In seven
      barbiturate-anesthetized rats, 16 vasomotor presympathetic neurons were filled
      with biotinamide and analyzed for the presence of tyrosine hydroxylase
      immunoreactivity and/or DNPI/VGLUT2 mRNA. Biotinamide-labeled neurons included C1
      and non-C1 cells. Most non-C1 (9/10) and C1 presympathetic cells (5/6) contained
      DNPI/VGLUT2 mRNA. In conclusion, DNPI/VGLUT2 is expressed by most blood pressure
      regulating presympathetic cells of the RVLM. The data suggest that these neurons
      may be glutamatergic and that the C1 adrenergic phenotype is one of several
      secondary phenotypes that are differentially expressed by subgroups of these
      cells.

PMID- 11840477
TI  - Orcokinin peptides in developing and adult crustacean stomatogastric nervous
      systems and pericardial organs.
AB  - The orcokinins are a family of neuropeptides recently isolated from several
      crustacean species. We found orcokinin-like immunoreactivity in the
      stomatogastric nervous systems and pericardial organs of three decapod crustacean
      species, Homarus americanus, Cancer borealis, and Panulirus interruptus. The
      neuropil of the stomatogastric ganglion was stained in adults of all three
      species as well as in embryonic and larval H. americanus. In H. americanus, the
      somata giving rise to this projection were found in the inferior ventricular
      nerve. Matrix-assisted laser desorption/ionization mass spectrometry mass
      profiling and sequencing with postsource decay led to the identification of six
      different orcokinin family peptides, including those previously described in
      other decapods and two novel shorter peptides. Application of exogenous
      [Ala(13)]orcokinin to the stomatogastric ganglion of H. americanus resulted in
      changes in the pyloric rhythm. Specifically, the number of lateral pyloric (LP)
      neuron spikes/burst decreased, and the phase of firing of the pyloric neurons was
      altered. Together, these data indicate that the orcokinins are likely to function
      as modulators of the crustacean stomatogastric ganglion.

PMID- 11840476
TI  - Trigeminal collaterals in the nasal epithelium and olfactory bulb: a potential
      route for direct modulation of olfactory information by trigeminal stimuli.
AB  - The nasal epithelium is richly invested with peptidergic (substance P and
      calcitonin gene-related peptide [CGRP]) trigeminal polymodal nociceptors, which
      respond to numerous odorants as well as irritants. Peptidergic trigeminal sensory
      fibers also enter the glomerular layer of the olfactory bulb. To test whether the
      trigeminal fibers in the olfactory bulb are collaterals of the epithelial
      trigeminal fibers, we utilized dual retrograde labeling techniques in rats to
      identify the trigeminal ganglion cells innervating each of these territories.
      Nuclear Yellow was injected into the dorsal nasal epithelium, and True Blue was
      injected into the olfactory bulb of the same side. Following a survival period of
      3-7 days, the trigeminal ganglion contained double-labeled, small (11.8 x 8.0
      microm), ellipsoid ganglion cells within the ethmoid nerve region of the
      ganglion. Tracer injections into the spinal trigeminal complex established that
      these branched trigeminal ganglion cells also extended an axon into the
      brainstem. These results indicate that some trigeminal ganglion cells with
      sensory endings in the nasal epithelium also have branches reaching directly into
      both the olfactory bulb and the spinal trigeminal complex. These trigeminal
      ganglion cells are unique among primary sensory neurons in having two branches
      entering the central nervous system at widely distant points. Furthermore, the
      collateral innervation of the epithelium and bulb may provide an avenue whereby
      nasal irritants could affect processing of coincident olfactory stimuli.

PMID- 11840478
TI  - Identification of orcokinins in single neurons in the stomatogastric nervous
      system of the crayfish, Cherax destructor.
AB  - The orcokinins are a highly conserved family of crustacean peptides that enhance
      hindgut contractions in the crayfish Orconectes limosus (Stangier et al. [1992]
      Peptides 13:859-864). By combining immunocytochemical and mass spectrometrical
      analysis of the stomatogastric nervous system (STNS) in the crayfish Cherax
      destructor, we show that multiple orcokinins are synthesized in single neurons.
      Immunocytochemistry demonstrated orcokinin-like immunoreactivity in all four
      ganglia of the STNS and in the pericardial organs, a major neurohaemal organ.
      Identified neurons in the STNS were stained, including a pair of modulatory
      interneurons (inferior ventricular nerve neuron, IVN), a neuron with its cell
      body in the stomatogastric ganglion that innervates cardiac muscle c6 via the
      anterior median nerves (AM-c6), and a sensory neuron (anterior gastric receptor
      neuron). Five orcokinin-related peptides were identified by matrix-assisted laser
      desorption ionization time of flight mass spectrometry (MALDI-TOF MS) post source
      decay fragmentation in samples of either the stomatogastric ganglion or the
      pericardial organs. Four of these peptides are identical to peptides derived from
      the cloned Procambarus clarkii precursor (Yasuda-Kamatani and Yasuda [2000] Gen.
      Comp. Endocrinol. 118:161-172), including the original [Asn(13)]-orcokinin
      (NFDEIDRSGFGFN, [M+H](+) = 1,517.7 Da), [Val(13)]-orcokinin ([M+H](+) = 1,502.7
      Da), [Thr(8)-His(13)]-orcokinin ([M+H](+) = 1,554.8 Da), and FDAFTTGFGHS
      ([M+H](+) = 1,186.5 Da). The fifth peptide is a hitherto unknown orcokinin
      variant: [Ala(8)-Ala(13)]-orcokinin ([M+H](+) = 1,458.7 Da). The masses of all
      five peptides were also detected in the inferior ventricular nerve of C.
      destructor, which contains the cell bodies and axons of the IVNs as well as the
      axons of two other orcokinin-like immunoreactive neurons. In the oesophageal
      nerve, in which all the orcokinin-like immunoreactivity derives from the IVNs, at
      least two of the orcokinins were detected, indicating that multiple orcokinins
      are synthesized in these neurons. Similarly, all four orcokinin masses were
      detected in the anterior median nerves, in which all the orcokinin-like
      immunoreactivity derives from the AM-c6 neuron. This study therefore lays the
      groundwork to investigate the function of the orcokinin peptide family using
      single identified neurons in a well-studied system.

PMID- 11840479
TI  - Expression of neuronal nicotinic acetylcholine receptor subunit mRNAs within
      midbrain dopamine neurons.
AB  - Many behavioral effects of nicotine result from activation of nigrostriatal and
      mesolimbic dopaminergic systems. Nicotine regulates dopamine release not only by
      stimulation of nicotinic acetylcholine receptors (nAChRs) on dopamine cell bodies
      within the substantia nigra and ventral tegmental area (SN/VTA), but also on
      presynaptic nAChRs located on striatal terminals. The nAChR subtype(s) present on
      both cell bodies and terminals is still a matter of controversy. The purpose of
      this study was to use double-labeling in situ hybridization to identify nAChR
      subunit mRNAs expressed within dopamine neurons of the SN/VTA, by using a
      digoxigenin-labeled riboprobe for tyrosine hydroxylase as the dopamine cell
      marker and (35)S-labeled riboprobes for nAChR subunits. The results reveal a
      heterogeneous population of nAChR subunit mRNAs within midbrain dopamine neurons.
      Within the SN, almost all dopamine neurons express alpha2, alpha4, alpha5,
      alpha6, beta2, and beta3 nAChR mRNAs, with more than half also expressing alpha3
      and alpha7 mRNAs. In contrast, less than 10% express beta4 mRNA. Within the VTA,
      a similar pattern of nAChR subunit mRNA expression is observed except that most
      subunits are expressed in a slightly lower percentage of dopamine neurons than in
      the SN. Within the SN, alpha4, beta2, alpha7, and beta4 mRNAs are also expressed
      in a significant number of nondopaminergic neurons, whereas within the VTA this
      only occurs for beta4. The heterogeneity in the expression of nAChR subunits
      within the SN/VTA may indicate the formation of a variety of different nAChR
      subtypes on cell bodies and terminals of the nigrostriatal and mesolimbic
      pathways.

PMID- 11840480
TI  - Glycine and GABA(A) receptor subunits on Renshaw cells: relationship with
      presynaptic neurotransmitters and postsynaptic gephyrin clusters.
AB  - Inhibitory synapses with large and gephyrin-rich postsynaptic receptor areas are
      likely indicative of higher synaptic strength. We investigated the presynaptic
      inhibitory neurotransmitter content (GABA, glycine, or both) and the presence and
      subunit composition of GABA(A) and glycine postsynaptic receptors in one example
      of gephyrin-rich synapses to determine neurochemical characteristics that could
      also contribute to enhance synaptic strength. Hence, we analyzed subunit receptor
      expression in gephyrin patches located on Renshaw cells, a type of spinal
      interneuron that receives powerful excitatory and inhibitory inputs and displays
      many large gephyrin patches on its surface. GABA(A) and glycine receptors were
      almost always colocalized inside Renshaw cell gephyrin clusters. According to the
      subunit-immunoreactivities detected, the composition of GABA(A) receptors was
      inferred to be either alpha(3)beta((2or3))gamma(2), alpha(5)beta((2or3))gamma(2),
      alpha(3)alpha(5)beta((2or3))gamma(2) or a combination of these. The types of
      neurotransmitters contained inside boutons presynaptic to Renshaw cell gephyrin
      patches were also investigated. The majority (60-75%) of terminals presynaptic to
      Renshaw cell gephyrin patches contained immunocytochemical markers for GABA as
      well as glycine, but a proportion contained markers only for glycine.
      Significantly, 40% of GABA(A) receptor clusters were opposed to presynaptic
      boutons that contained only glycinergic markers. We postulate that GABA and
      glycine corelease, and the presence of alpha3-containing GABA(A) receptors can
      enhance the postsynaptic current and contribute to strengthen inhibitory input on
      Renshaw cells. In addition, a certain degree of imprecision in the localization
      of postsynaptic GABA(A) receptors in regard to GABA release sites onto adult
      Renshaw cells was also found.

PMID- 11840481
TI  - The end of the beginning of chromosome ends.

PMID- 11840482
TI  - Detecting rearrangements in children using subtelomeric FISH and SKY.
AB  - The etiology of mental retardation (MR), often presenting as developmental delay
      in childhood, is unknown in approximately one-half of cases. G-banding is the
      standard method for investigating those suspected of having a chromosomal
      etiology; however, detection of structural abnormalities is limited by the size
      and pattern of the G-bands involved. Rearrangements involving subtelomeric
      regions have been shown to cause MR and this has generated interest in
      investigating the prevalence of these rearrangements using telomere-specific
      probes. In addition, because cryptic interchromosomal rearrangements may not be
      small or confined to chromosomal ends, spectral karyotyping (SKY) using
      chromosome-specific painting probes may be of value. We report here a study using
      these two FISH-based techniques in 50 children with idiopathic MR or
      developmental delay and normal GTG-banded karyotypes. Our objective was to assess
      the prevalence of cryptic rearrangements in this population using subtelomeric
      FISH and SKY. Three rearrangements were detected by subtelomeric FISH: a
      derivative 5 from a maternal t(5;21); a recombinant 11 from a paternal
      pericentric inversion; and a 2q deletion that was also present in the mother.
      Only the derivative 5 was detected by SKY. SKY did not detect any interstitial
      interchromosomal rearrangement. The prevalence of clinically significant cryptic
      rearrangements by subtelomeric FISH and SKY was thus 4% (95% confidence interval
      0.5-13.7) and 2% (95% CI 0.05-10.7), respectively. This study supports the view
      that G-banding does not detect all clinically significant chromosomal
      abnormalities and that subtelomeric FISH and SKY can detect some of these
      abnormalities.

PMID- 11840483
TI  - Subtelomeric rearrangements detected in patients with idiopathic mental
      retardation.
AB  - A screening for submicroscopic rearrangements was performed in 111 patients with
      idiopathic mental retardation (MR) using fluorescence in situ hybridization
      (FISH) probes from the subtelomeric regions of all chromosome arms. Ten cryptic
      rearrangements were found (9%): five de novo deletions; one unbalanced de novo
      translocation; three unbalanced inherited translocations; and one unbalanced
      recombinant chromosome, inherited from a parent with a pericentric inversion. In
      addition, 50 of the patients were screened for interstitial rearrangements with
      spectral karyotyping (SKY), but no aberrations were found. However, SKY detected
      the subtelomeric rearrangement in three of the four unbalanced translocations.
      Dysmorphic features were present in all patients with detected subtelomeric
      rearrangements.

PMID- 11840484
TI  - Study of 250 children with idiopathic mental retardation reveals nine cryptic and
      diverse subtelomeric chromosome anomalies.
AB  - Cryptic subtelomeric chromosome anomalies have been recognized as a significant
      cause of dysmorphology and mental retardation. To determine whether the clinical
      cytogenetics laboratory should screen routinely for these aberrations, we have
      tested 250 patients with idiopathic mental retardation/developmental delay,
      either isolated (53) or associated with dysmorphic features and/or malformations
      in the absence of a recognizable syndrome (197). All had normal karyotypes at the
      550-850 band level. Subtelomeric anomalies were found in 1/53 of the first group
      (1.9%) and 8/197 of the second group (4.1%). In one patient, two separate
      anomalies were present: a deletion (not inherited) and a duplication (inherited).
      It is possible that one of these 10 observed aberrations might represent a rare
      and previously unreported polymorphism and one a rare cross-hybridization. Our
      study supports the proposition that cryptic subtelomeric rearrangements are a
      significant cause of idiopathic mental retardation/developmental delay, but both
      the diversity of the phenotypes of the positive cases and the wide diversity of
      their associated chromosome abnormalities emphasize the central problem for the
      clinical cytogenetics laboratory-that of choosing the most productive patient
      base for this useful diagnostic test.

PMID- 11840485
TI  - Association of tetralogy of Fallot with a distinct region of del22q11.2.
AB  - Congenital heart defects (CHDs) appear in greater frequency among relatives of
      patients and in individuals with DiGeorge syndrome (DGS) or velo-cardio-facial
      syndrome (VCFS). A majority of these patients and part of the apparently
      nonsyndromic CHD patients with conotruncal defects manifest hemizygous deletions
      within chromosome 22q11.2 (del22q11). We tested myocardial tissues of 31 CHD
      patients, 21 with tetralogy of Fallot (TOF) and 10 with a double-chamber right
      ventricle (DCRV). DNA isolated from tissues removed at corrective surgery was
      analyzed for homo- or heterozygosity of nine polymorphic short tandem repeat
      (STR) markers along the 22q11.2 region. DNA from the blood of 45 healthy
      individuals represented the general population. Ten of the 21 TOF patients (48%)
      showed homozygosity for three or more consecutive markers, indicating deletions
      of various sizes. No such indication was found for DCRV patients. Heterozygosity
      for markers D22S1648, D22S941, and D22S944 was lower in the TOF group than in
      normal controls, defining a minimal critical region (MCR) for the deletion. Our
      findings support an association between TOF and hemizygosity in 22q11.2,
      suggesting a distinct region, between markers D22S1638 and COMT, that may harbor
      TOF susceptibility genes.

PMID- 11840486
TI  - Detection of Y-specific sequences in 122 patients with Turner syndrome: nested
      PCR is not a reliable method.
AB  - The incidence of Y chromosome sequences in patients with Turner syndrome has been
      evaluated in several studies, and its frequency varied from 0% to 61%, depending
      on the molecular methodology used. The aim of our study was to screen for Y
      chromosome sequences in 122 patients with Turner syndrome without cytogenetic
      evidence of this chromosome. DNA of 100 normal women was also screened and it was
      used as a negative control. To identify cryptic Y mosaicism, eight regions of Y
      chromosome were amplified by PCR. In order to increase the sensitivity of Y
      sequence detection, a nested PCR of the SRY and TSPY genes was also performed.
      All patients had several stigmata of Turner syndrome and none of them presented
      with signs of virilization. The most frequent karyotype was 45,X (54.1%),
      followed by mosaicism involving structural aberration of the X chromosome. There
      were 12 patients who carried a marker or ring chromosome. First-round PCR
      identified Y chromosome sequences in only four patients (3%), and all of them had
      a chromosome mosaicism with at least one cell lineage with a marker chromosome.
      After nested PCR, 25% of the patients and 14% of the normal women were positive
      for the presence of Y sequences. Contamination with extraneous genomic DNA was
      ruled out by microsatellite studies, but we cannot eliminate the possibility of
      contamination with PCR products, despite careful handling. We conclude that
      nested PCR overestimated the frequency of Y sequences in patients with Turner
      syndrome and should be avoided to prevent false positive results, which lead to
      unnecessary surgical treatment of these patients.

PMID- 11840487
TI  - Idiopathic congenital central hypoventilation syndrome: evaluation of brain
      derived neurotrophic factor genomic DNA sequence variation.
AB  - Idiopathic congenital central hypoventilation syndrome (CCHS) is an unique
      disorder of respiratory control, occurring in association with Hirschsprung
      disease (HSCR), tumors of neural crest origin, and symptoms of autonomic nervous
      system dysfunction (ANSD). CCHS is thought to be genetic in origin based upon 1)
      affected sib pairs, 2) genetic analysis, and 3) identification of genetic
      mutations in both HSCR and CCHS patients. Because these mutations have been found
      in but a few cases of CCHS, exploration of other candidate genes has continued.
      Brain-derived neurotrophic factor (BDNF) represents a potential candidate gene to
      consider because of altered respiratory control in the BDNF knock-out mouse model
      and localization to the enteric nervous system in human tissue. The objective of
      this study was to determine the frequency of BDNF mutations among 19 children
      with CCHS (five with HSCR) compared to 40 unaffected unrelated controls. Using
      the known genomic DNA sequence for BDNF, polymerase chain reaction (PCR)
      amplified genomic DNA was analyzed by standard sequencing methods. A discrete
      mutation was identified in one of 19 children with isolated CCHS and the
      unaffected father. Specifically, an isoleucine was substituted for a threonine or
      serine in the amino acid sequence. Absence of this mutation in 40 controls
      confirmed that this mutation was likely not a common polymorphism. These data
      further support a genetic basis for CCHS, though mutations of BDNF are not
      consistent in this disorder.

PMID- 11840488
TI  - Association analysis of polymorphisms at the interleukin-1 locus in essential
      hypertension.
AB  - Infection with microorganisms such as Helicobacter pylori and Chlamydia
      pneumoniae has been associated with coronary heart disease (CAD) and hypertension
      (HT). Infection increases the release of pro-inflammatory cytokines, thus
      facilitating interactions that lead to vascular damage and other effects. We
      hypothesized that genetically determined differences in activity or
      responsiveness of cytokine(s) might contribute to HT. The interleukin-1 gene
      (IL1) cluster on chromosome 2q14 contains three related genes (IL1A, IL1B, and
      IL1RN) located within a 430-kb region. These encode IL-1alpha and IL-1beta, as
      well as their endogenous receptor antagonist, IL-1ra. The IL1RN gene has a penta
      allelic 86-bp tandem repeat in intron 2. Allele IL1RN* 2 is associated with a
      wide range of chronic inflammatory and autoimmune conditions, and its combination
      with the -31T variant of an IL1B C(-31)T polymorphism constitutes a pro
      inflammatory haplotype that leads to vigorous IL-1beta production. We therefore
      tested each of these polymorphisms for association with HT. Subjects were white
      Anglo-Celtic residents of Sydney, Australia. Frequencies of IL1B C(-31)T
      genotypes CC, CT, and TT were 0.50, 0.40, and 0.10 in normotensive (NT) and 0.46,
      0.46, and 0.08 in HT, respectively (chi(2) = 1.2, P = 0.55). T allele frequency
      in NT (0.30) was similar to that in HT (0.31). For the IL1RN variant, frequencies
      of alleles IL1RN* 1 and * 2 and combined minor alleles * 3, * 4, and * 5 were
      0.61, 0.36, and 0.03 in NT and 0.54, 0.36, and 0.10 in HT, respectively (chi(2) =
      11, P = 0.004). In conclusion, no association of the IL1B C(- 31)T with HT was
      found, whereas combined frequency of the minor alleles of the IL1RN polymorphism
      was increased in the HT cohort studied.

PMID- 11840489
TI  - Craniofacial phenotypes in segmentally trisomic mouse models for Down syndrome.
AB  - Trisomy for chromosome 21 (Chr 21) has profound effects on development that
      result in a constellation of phenotypes known as Down syndrome (DS). Distinctive
      craniofacial manifestations are among the few features common to all individuals
      with DS. The characteristic face of a person with DS results primarily from
      maldevelopment of the underlying craniofacial skeleton. The Ts65Dn mouse, which
      has segmental trisomy 16, producing dosage imbalance for about half the genes
      found on human Chr 21, exhibits specific skeletal malformations corresponding
      directly to the craniofacial dysmorphogenesis in DS. Here we demonstrate that
      Ts1Cje mice, which are at dosage imbalance for about 3/4 of the genes triplicated
      in Ts65Dn, demonstrate a very similar pattern of anomalies in the craniofacial
      skeleton. However, one characteristic of Ts65Dn mice, a broadening of the cranial
      vault contributing to brachycephaly, is not seen in Ts1Cje mice. These
      observations independently confirm that a dosage imbalance for mouse genes
      orthologous to those on human Chr 21 has corresponding effects in both species.
      The subtle differences in the craniofacial phenotypes of Ts1Cje and Ts65Dn mice
      have implications for elucidation of the mechanisms by which this aneuploidy
      disrupts development.

PMID- 11840490
TI  - Acute hemorrhagic leukoencephalitis in male sibs.
AB  - Male siblings developed acute hemorrhagic leukoencephalitis (AHL) at age five
      months and eight months, respectively. This rare condition has not been reported
      in individuals less than two years of age or with a recurrence in the family. The
      diagnosis was based on neuropathologic features after ruling out potentially
      mimicking conditions. Genetic counseling of early onset AHL should include the
      possibility of recurrence in siblings.

PMID- 11840491
TI  - Hypoplastic left heart in a female infant with partial trisomy 4q due to de novo
      4;21 translocation.
AB  - We present a female infant with mild dysmorphic features and congenital heart
      defect: hypoplastic left heart with aortic atresia and hypoplastic aortic arch,
      ventricular septal defect, and a nonrestrictive atrial communication. Chromosome
      analysis showed an unbalanced translocation that contained additional material
      from 4q translocated onto 21q. This resulted in partial trisomy 4 and monosomy
      for the 21q telomeric region. The derivative chromosome was characterized using G
      banding, M-FISH, and whole chromosome painting. The karyotype was described as
      46,XX,der(21)t(4;21)(q25;q22.3).ish(wcp4+;wcp21+). Additional analyses with FISH
      probes specific for 21q 22.3, 21q22.2, 21q21.1, and 21q11.2 did not indicate any
      chromosome 21 duplication within the derivative chromosome 21. Monosomy for the
      telomeric portion of 21q was demonstrated using a tel 21q probe (Oncor). The
      patient underwent stage 1 Norwood procedure to manage her heart defect. Poor
      feeding and failure to thrive complicated the postsurgical period. The child
      subsequently underwent funduplication and feeding tube placement, and at 4.5
      months of age presented with microcephaly and developmental delay. Hypoplastic
      left heart was previously reported with increased frequency in relatively common
      numeric chromosomal aberrations, such as monosomy X, trisomies 21, 18, and 13,
      and in various structural chromosomal defects. Our report presents new evidence
      for the co-occurrence of hypoplastic left heart with a duplicated portion of
      chromosome 4 distal to 4q25. In addition, monosomy for the telomeric region of
      chromosome 21 may have implications in the phenotype.

PMID- 11840492
TI  - Paternal origin of a small, class I inv dup(15).

PMID- 11840493
TI  - Amyoplasia associated with a balanced de novo insertion of a segment of the long
      arm of chromosome 5 into chromosome 2.

PMID- 11840494
TI  - Reproductive risks for paracentric inversion heterozygotes: Inversion or
      insertion? That is the question.

PMID- 11840495
TI  - Comparison of FMR1-protein expression in lymphocytes, methylation pattern in
      Southern blot analysis, and IQ values in three sisters with the fragile X
      syndrome.

PMID- 11840496
TI  - Benign mental health consequences of screening for mutations of BRCA1/BRCA2.

PMID- 11840498
TI  - Genetic association mapping at the crossroads: which test and why? Overview and
      practical guidelines.
AB  - Until about a decade ago, genetic association testing essentially meant case
      control association analysis using genetic markers. Concerns about population
      stratification propelled family-based tests of association into widespread use
      and challenged the classic case control design. The literature now contains a
      vast collection of different family-based methods, most of which are based on the
      transmission/disequilibrium test (TDT). Some methods extend the original TDT to
      accommodate multiallelic markers, variable pedigree constellations, multiple
      loci, etc. Other methods go beyond the original design of the TDT to detect
      genetic association via haplotype sharing. Most recently, we have witnessed a
      revival of case control methods that control for population stratification. The
      purpose of this review is to help orient readers to the rapidly developing
      methods of association testing and enhance their understanding of the basic
      principles of these approaches. We present an overview of the development of
      genetic association tests, with practical guidelines on which test might be the
      most suitable for a given study.

PMID- 11840499
TI  - Human metabotropic glutamate receptor 2 gene (GRM2): chromosomal sublocalization
      (3p21.1-p21.2) and genomic organization.
AB  - Imbalances in glutamatergic function have been implicated in the pathogenesis of
      neuropsychiatric disorders. Consequently, glutamate receptors genes are promising
      candidates in search of susceptibility genes for these disorders. In the present
      study, we report the chromosomal sublocalization and genomic organization of the
      human metabotropic glutamate receptor 2 gene (GRM2). Using monochromosomal hybrid
      cell lines of NIGMS Mapping Panel 2 (Coriell Cell Repository), the GRM2 gene was
      localized to human chromosome 3, confirming previously reported localization. In
      addition, using the radiation hybrid panel RH3 (Research Genetics), we
      sublocalized the GRM2 gene to chromosomal region 3p21.1-p21.2. The genomic
      organization of the GRM2 gene was established using a premade library of adaptor
      ligated, human-specific genomic DNA fragments. The gene consists of 5 exons, with
      sizes ranging from 74 to 1,076 bp.

PMID- 11840500
TI  - Mutation analysis of the retinoid X receptor beta, nuclear-related receptor 1,
      and peroxisome proliferator-activated receptor alpha genes in schizophrenia and
      alcohol dependence: possible haplotype association of nuclear-related receptor 1
      gene to alcohol dependence.
AB  - Because retinoid cascades are involved in the regulation and development of the
      central nervous system, including dopaminergic neurons, retinoic acid signaling
      defects may contribute to schizophrenia and substances dependence. Retinoid X
      receptors (RXRs) form heterodimer complexes with nuclear-related receptor 1
      (NURR1) or with peroxisome proliferator-activated receptors (PPARs). We examined
      48 Japanese patients with schizophrenia and 32 patients with alcohol dependence
      to detect mutations in the retinoid X receptor beta gene (RXRB) on chromosome
      6p21.3, the NURR1 gene (NR4A2) on chromosome 2q22-q23, and the PPAR alpha gene
      (PPARA) on chromosome 22q12.2-13.1. A Val95Ala polymorphism of the RXRB gene, a
      Val227Ala polymorphism in the PPARA gene, and two synonymous single-nucleotide
      and CA repeat polymorphisms in the 5' region and 3' untranslated region of the
      NR4A2 gene were identified. Extended case control samples did not suggest an
      association between the diseases and the RXRB or PPARA polymorphisms. However,
      they revealed a significant association between the NR4A2 gene haplotype and
      alcohol dependence, indicating that 2q22-q23 including the NR4A2 gene locus is a
      possible genomic region contributing to genetic susceptibility to alcohol
      dependence.

PMID- 11840501
TI  - Lack of association between HoxA1 and HoxB1 gene variants and autism in 110
      multiplex families.
AB  - A recent report suggested that the HoxA1 and/or HoxB1 genes play a role in
      susceptibility to autism. To determine whether these findings could be confirmed,
      we screened these genes for DNA polymorphisms by sequencing all exons in 24
      individuals with autism. We identified the same sequence variants in the genes
      that appeared in this report, which include one single-base substitution variant
      in HoxA1 and a common haplotype in HoxB1. We performed an association study by
      applying the transmission disequilibrium test to detect possible association of
      these variants to autism in 110 multiplex families. Our results demonstrated no
      deviation from the null hypothesis of no association. We have also separately
      examined transmissions within individual mating types, for paternal versus
      maternal alleles, to affected versus unaffected children, and for transmission to
      affected boys versus girls. None of these subsets revealed significant deviation
      from the null expectation. Our interpretation of these findings is that it is
      unlikely that HoxA1 and HoxB1 play a significant role in the genetic
      predisposition to autism.

PMID- 11840502
TI  - Lack of association between cathepsin D genetic polymorphism and Alzheimer
      disease in a Spanish sample.
AB  - Cathepsin D (catD) is an intracellular aspartyl protease that exhibits beta and
      gamma secretase-like activity to cleave amyloid precursor protein into beta
      amyloid peptide. The T-allele of a biallelic (alleles C and T) polymorphism in
      the exon 2 of the catD gene has been found to be associated with increased risk
      of Alzheimer disease (AD) in two independent German populations. Other groups
      have been unable to replicate this association in Caucasian American and Northern
      Ireland populations. Moreover, a small and no significant tendency for the T
      allele to be protective for AD has been demonstrated in Caribbean Hispanics. A
      case control study utilizing a clinically well-defined group of 311 sporadic AD
      patients and 346 control subjects was performed to test this association in an
      ethnically homogeneous population from Spain. We did not observe any association
      between the T-allele of the catD gene and the disease. Furthermore, catD was not
      predictive of AD in an interactive fashion when considering apolipoprotein E,
      age, or gender.

PMID- 11840503
TI  - Mutation screening of the dopamine D2 receptor gene in attention-deficit
      hyperactivity disorder subtypes: preliminary report of a research strategy.
AB  - Attention-deficit hyperactivity disorder (ADHD) is a highly heritable syndrome
      with onset in childhood that is associated with clinical response to drugs, which
      increase the release of monoamines, especially dopamine. A variety of studies
      have reported on genetic associations of ADHD with polymorphisms for various
      component genes of the dopamine pathway. The promise of preliminary associations
      found with several genes is mitigated by the significant controversy that exists
      over what are the appropriate clinical characteristics of ADHD associated with
      its familial transmission. In the current report, we describe a strategy for
      mutation screening in common, complex disorders and its application to the
      systematic screening for coding region variation in the dopamine D2 receptor
      (DRD2) gene. We used groups of individuals who met diagnostic criteria for DSM-IV
      defined ADHD subtypes, as well as recently defined latent class criteria for pure
      familial forms of ADHD. No coding region sequence variations were identified in
      the DRD2 gene that met our requirements for prevalence to be considered a
      candidate variant contributing to susceptibility for ADHD.

PMID- 11840504
TI  - HLA class I distribution in Japanese patients with schizophrenia.
AB  - Several Caucasian studies and one Japanese study have observed associations
      between human leukocyte antigen (HLA) class I specificities, including A24 (9)
      and A26 (10) and schizophrenia. Most of those studies were conducted in 1970s and
      early 1980s, when the typing technique of HLA was not adequately reliable. Also,
      an operational diagnostic system was not employed in many of the studies. The
      present study investigated frequencies of HLA-A specificities in schizophrenia
      patients (ICD-10 and DSM-III-R, n=98) and sex-matched healthy controls (n=392)
      from population in the southwestern part of Japan. HLA-B and -C specificities
      were studied in addition. Frequencies of subjects possessing A24 and A26 were not
      different between the patients and controls (54% and 24% in the patients and 62%
      and 24% in the controls, respectively). No significant difference was found in
      frequencies of other class I (A, B, and C) specificities between the patients and
      the controls. Thus, the present study provided no evidence for an association
      between the HLA class I specificities, including A24, A26, and others, and
      schizophrenia in the Japanese population.

PMID- 11840505
TI  - Metabotropic glutamate receptor 3 (GRM3) gene variation is not associated with
      schizophrenia or bipolar affective disorder in the German population.
AB  - In the present study, we sought to identify genetic variation in the metabotropic
      glutamate receptor 3 (GRM3) gene, which has been mapped to chromosome 7q21.1
      q21.2 [Scherer et al., 1996] and might contribute to genetic predisposition to
      schizophrenia and/or bipolar affective disorder. Using single-strand conformation
      analysis (SSCA), we screened the complete coding sequence as well as adjacent
      splice sites of the GRM3 gene in a sample of 46 bipolar affective and 46
      schizophrenic patients. We detected three sequence variants: a rare C/T
      substitution at nucleotide position +885 (T209T), a C/T substitution at
      nucleotide position +2130 (Y624Y), and a more common C/T substitution at
      nucleotide position +1131 (A291A). The occurrence of the +1131C/T variant was
      investigated in a sample of bipolar affective patients (n=283), schizophrenic
      patients (n=265), and ethnically matched controls (n=227). We observed a
      significant overrepresentation of the +1131T allele in schizophrenic patients
      when compared to controls (P=0.0022). This finding was followed up in an
      independent sample of schizophrenic patients (n=288) and controls (n=162) and 128
      schizophrenic trios but could not be confirmed. It is therefore unlikely that
      this variant plays a major role in predisposing to schizophrenia and/or bipolar
      affective disorder at least in the German population.

PMID- 11840506
TI  - Chromosome 1q12-q22 linkage results in eastern Quebec families affected by
      schizophrenia.
AB  - An impressive LOD score of 6.5 has recently been reported for schizophrenia on
      chromosome 1q21-22 in large families from eastern Canada [Brzustowicz et al.,
      2000: Science 288:678-682]. We did not reproduce such a finding in large
      pedigrees of eastern Quebec based on seven markers spanning the 1p13-1q22 region
      and using both the models and phenotypes of Brzustowicz et al. and those used in
      our ongoing genome scan in 21 large French Canadian families. There was no
      significant total LOD scores in that chromosomal region (a maximum of 0.57)
      either for schizophrenia or bipolar disorders, nor any signal in individual large
      pedigrees. However, the samples of Brzustowicz et al. and ours differed in terms
      of their origins, the latter being of French ancestry and the former of Celtic
      and German descent. Population difference, genetic heterogeneity, and differences
      in ascertainment might explain the lack of replication. The result reported by
      Brzustowicz et al. cannot be discarded and should probably be considered as a
      susceptibility locus for a subset of the schizophrenic population.

PMID- 11840507
TI  - Motor immaturity and specific speech and language impairment: evidence for a
      common genetic basis.
AB  - Previous studies have found an association between motor immaturity and specific
      language impairment in children. Data from two twin studies were used to address
      the question of whether these linked deficits have a common etiology. Study 1
      involved 57 MZ and 22 DZ pairs where one or both twins had specific
      speech/language impairment. A control group of 173 single-born children was also
      tested. Motor skill was assessed using a tapping task, which was carried out with
      left and right hands. Tapping scores were converted to scaled scores adjusted for
      age and sex. Unaffected twins and single-born controls did not differ in motor
      skill, but twins with speech and/or language impairments obtained significantly
      poorer tapping scores than controls. Bivariate DeFries-Fulker analysis pointed to
      shared genetic influence on tapping speed and a measure of speech production
      accuracy. In study 2, 37 twin pairs from study 1 were retested 2-3 years later
      and combined with 100 twin pairs from a general population sample. A timed peg
      moving task was used to assess motor skill. Children with combined speech and
      language impairments obtained poorer peg-moving scores than unaffected children.
      Bivariate DeFries-Fulker analysis found significant shared genetic variance for
      impairments on peg-moving and on a test of nonword repetition. It is concluded
      that genes that put the child at risk for communicative problems also affect
      motor development, with the association being most evident when speech production
      is affected.

PMID- 11840508
TI  - Symptom domains in autism and related conditions: evidence for familiality.
AB  - Heterogeneity in autism impairs efforts to localize and identify the genes
      underlying this disorder. As autism comprises severe but variable deficits and
      traits in three symptom domains (social interaction, communication, and
      repetitive behaviors) and shows variability in the presence and emergence of
      useful phrase speech, different genetic factors may be associated with each. The
      affected cases (n=457) in multiply affected siblingships (n=212), including a
      proband with autism and one or more siblings with either autism or marked
      deficits in autism symptom domains, were assessed using the Autism Diagnostic
      Interview, Revised. Symptom domain scores and language features were examined to
      determine their similarity within siblingships. The variance within siblingships
      was reduced for the repetitive behavior domain and for delays in and the presence
      of useful phrase speech. These features and the nonverbal communication subdomain
      provided evidence of familiality when we considered only the diagnosis of autism
      to define multiply affected siblingships (cases: n=289; siblingships: n=136). In
      addition, the same familial features identified also appeared familial for those
      with autism-related conditions. Finally, the level of severity of almost all of
      the familial features varied within multiplex siblingships independently. The
      features identified as familial replicate the combined set suggested in earlier,
      smaller studies. Furthermore, the familiality of these features extend to related
      conditions of milder severity than autism and appear to be independent. Making
      distinctions among families by the severity of these features may be useful for
      identifying more genetically homogeneous subgroups in studies targeted at genes
      for specific autism-related symptom domains.

PMID- 11840509
TI  - Association between a polymorphism in the pseudoautosomal X-linked gene SYBL1 and
      bipolar affective disorder.
AB  - In the past decade, several chromosomal regions have been analyzed for linkage
      with bipolar affective disorder (BPAD). There have been conflicting results
      regarding the involvement of X-chromosomal regions in harboring susceptibility
      genes for BPAD. Recently, a new candidate gene (SYBL1) for BPAD has been
      described on Xq28. SYBL1, which maps to the Xq pseudoautosomal region (PAR),
      encodes a member of the synaptobrevin family of proteins involved in synaptic
      vesicle docking, exocytosis, and membrane transport. A subsequent case-control
      association study, including 110 US-American patients with BPAD and 119 unrelated
      controls, investigated a potential etiological role of a novel polymorphism (G-
      >C transversion) in a regulatory region of the SYBL1 gene. In this analysis, the
      C allele showed a statistical trend to be more frequent in males with BPAD than
      in respective controls (P=0.06). This finding prompted us to verify whether a
      similar effect was also present in a larger German sample of 164 unrelated
      patients with BPAD (148 patients with BP I disorder, 16 patients with BP II
      disorder) and 267 controls. We observed a significantly increased frequency of
      genotypes homozygous for the C allele in females with BPAD in comparison with
      controls (P=0.017). Thus, our data strengthen the role of the SYBL1 gene as a
      candidate gene for BPAD.

PMID- 11840510
TI  - Mutation analysis of synapsin III gene in schizophrenia.
AB  - Synapsin III is a new synapsin family gene with the putative function of
      synaptogenesis regulation and neurotransmitter release in the brain. The gene was
      mapped to 22q12-q13, a schizophrenia susceptible region gene as suggested by
      several linkage studies. Hence, the synapsin III gene is considered a candidate
      gene of schizophrenia. We systematically sequenced the protein coding and 5'
      promoter regions of the synapsin III gene to look for mutations in 62 Han Chinese
      schizophrenic patients from Taiwan with positive family history. Further case
      control association study was performed among 163 patients and 151 controls using
      the genetic polymorphic markers identified from these 62 patients. Three single
      nucleotide polymorphisms (SNPs) were identified: g.-631C > G and g.-196G>A at 5'
      promoter region, and g.69G>A at exon 1. Besides, no other mutations were
      identified in these patients. The g.69G>A polymorphism does not alter the amino
      acid threonine at codon 23 (ACG>ACA). Further case-control association studies
      also did not find significant differences of genotype or allele frequency
      distributions of these three polymorphisms between 163 patients and 151 non
      psychotic comparison individuals. Hence, our data are not in favor of a large
      effect of synapsin III gene in the pathogenesis of schizophrenia.

PMID- 11840511
TI  - Molecular analysis, mutation screening, and association study of adenylate
      cyclase type 9 gene (ADCY9) in mood disorders.
AB  - Chromosome 16p13 has been shown to display modest linkage signals for mood
      disorders in a number of studies. An interesting candidate gene in this region is
      the adenylate cyclase (AC) type 9 gene (ADCY9). ACs are critical in neuronal
      signaling, and perturbation of brain AC activity has been reported in mood
      disorder postmortem brains. ACs may also act as targets of antidepressants. Two
      distinct length transcripts for the ADCY9 gene have been reported, but molecular
      mechanisms are unknown. To investigate the potential role of ADCY9 in mood
      disorders, we clarified alternative poly(A) sites for the two mRNA species,
      delineated the exon-intron structure, and screened the gene for genetic variants.
      The two transcripts encoded by ADCY9 shared the first 10 exons, but exon 11 was
      shorter in one of the mRNA species. Seven single nucleotide polymorphisms,
      including a missense mutation and one polymorphic microsatellite repeat in the 3'
      UTR, were identified. However, a case-control study using the missense
      polymorphism, 2316A>G (Ile772Met), and the tetranucleotide repeat (TTTA)n showed
      no significant association with mood disorders in Japanese samples. The DNA
      polymorphisms detected in this study can be tested in other ethnic samples and/or
      other psychiatric diseases.

PMID- 11840512
TI  - Reduced size of the amygdala in individuals with 47,XXY and 47,XXX karyotypes.
AB  - The excess of 47,XXX and 47,XXY karyotypes found in cytogenetic screening studies
      of individuals with schizophrenia has given support for an increased risk of
      psychiatric illness among men and women with sex chromosomal aneuploidy (SCA).
      Mesial temporal lobe structures, including the amygdala and hippocampus, are
      thought to be associated with abnormalities of mood and behavior in humans and in
      the neurobiology of schizophrenia. This study focuses on variations in volumes of
      mesial temporal lobe structures in men and women with SCA. Utilizing an
      unselected birth cohort of subjects with SCA and high-resolution magnetic
      resonance imaging (MRI), we investigated the neuroanatomical consequences of a
      supernumerary X chromosome on the morphology of the amygdala and hippocampus.
      Regional and total brain volumes were measured in 10 subjects with 47,XXY, 10
      subjects with 47,XXX, and 20 euploid controls. Amygdala volumes were
      significantly reduced in men with 47,XXY, compared to control men, while the
      decrease in women with 47,XXX was not as pronounced. Hippocampus volumes were
      preserved in both groups, compared to same-gender controls. Longitudinal studies
      of SCA individuals have shown an increased incidence of mild psychopathology and
      behavioral dysfunction in men with 47,XXY and more overt psychiatric illness in
      women with 47,XXX, compared to control populations. The alteration in amygdala
      volumes in individuals with a supernumerary X chromosome may provide a
      neuroanatomic basis for these findings.

PMID- 11840513
TI  - Genomic screen and follow-up analysis for autistic disorder.
AB  - Autistic disorder (AutD) is a neurodevelopmental disorder characterized by
      significant impairment in social, communicative, and behavioral functioning. A
      genetic basis for AutD is well established with as many as 10 genes postulated to
      contribute to its underlying etiology. We have completed a genomic screen and
      follow-up analysis to identify potential AutD susceptibility loci. In stage one
      of the genome screen, 52 multiplex families (two or more AutD affected
      individuals/family) were genotyped with 352 genetic markers to yield an
      approximately 10 centimorgan (cM) grid, inclusive of the X chromosome. The
      selection criterion for follow-up of interesting regions was a maximum
      heterogeneity lod score (MLOD) or a maximum nonparametric sib pair lod score
      (MLS) of at least 1.0. Eight promising regions were identified on chromosomes 2,
      3, 7, 15, 18, 19, and X. In the stage two follow-up study we analyzed an
      additional 47 multiplex families (total=99 families). Regions on chromosomes 2,
      3, 7, 15, 19, and X remained interesting (MLOD> or =1.0) in stage two analysis.
      The peak lod score regions on chromosomes 2, 7, 15, 19, and X overlap previously
      reported peak linkage areas. The region on chromosome 3 is unique.

PMID- 11840514
TI  - No association between the WNT2 gene and autistic disorder.
AB  - Autistic disorder is a pervasive neurodevelopmental disorder characterized by
      deficits in language and social communication, as well as stereotyped patterns of
      behavior. Peak LOD scores from several genomic screening efforts indicate the
      presence of an autistic disorder susceptibility locus within the distal long arm
      of human chromosome 7 (7q31-q35). Wassink et al. [2001: Am J Med Genet 105:406
      413] reported that WNT2, located at 7q31, influences genetic risk in autistic
      disorder. These findings were enhanced when examined in a subset of families with
      severe language impairment. WNT genes encode secreted growth factor-like proteins
      that participate in growth regulation, differentiation, and tumorigenesis. We
      tested for genetic association of two WNT2 variants in an independent data set of
      135 singleton and 82 multiplex families. No significant association was found
      between autistic disorder and the WNT2 genotypes in either the overall data set
      or in the language-impaired subset of families. However, differences in allele
      frequencies of the 3' UTR single nucleotide polymorphism between the present
      population and that of Wassink et al. may account for the inability to detect
      association between WNT2 and autistic disorder in the present data set. We also
      screened the two reported autistic disorder mutations previously detected by
      Wassink et al. We did not identify any activating mutation in the coding region
      of the WNT2 gene. Thus, we conclude that activating mutations of the WNT2 gene
      are not a major contributor to the development of autistic disorder in these
      data.

PMID- 11840515
TI  - Association studies of the HOPA dodecamer duplication variant in different
      subtypes of autism.
AB  - The HOPA gene in Xq13 is coding for a protein involved in a nuclear thyroid
      receptor complex. Previous studies suggested association of the dodecamer
      duplication in the OPA-repeat region in exon 43 (according to the genomic
      database sequence) with autism, mental retardation, and
      schizophrenia/hypothyroidism. We determined the frequency of this 12 bp
      duplication variant in a sample of 155 patients divided in different subtypes of
      autism, 278 parents of those patients, and 157 control individuals. The allele
      frequency of the duplication variant was not significantly different between
      autistic patients, their parents, and the control group. Therefore, it is
      unlikely that this 12 bp duplication variant of the HOPA gene has major relevance
      to the susceptibility to different subtypes of autism at least in this German
      patient sample. In addition, we identified a third variant with a 15 bp deletion
      in the OPA-repeat region, recently described by another group, in one autistic
      patient. This third allele was also present in the patient's nonautistic mother
      and sister, who are heterozygous for this variant, but could not be detected in
      any other individual genotyped in this study. Expression analysis revealed
      transcription of all three allelic variants in lymphoblastoid cell lines.
      Furthermore, we identified a new splice variant that utilizes an additional 9 bp
      of the 3' intron subsequent to exon 39. Both alternative transcripts are
      coexpressed in all fetal and adult tissues examined.

PMID- 11840517
TI  - Proceedings of the Meeting of the International Council of Electrophoresis
      Societies. Verona, Italy, June 10-13, 2001.

PMID- 11840516
TI  - Association between the COMT locus and obsessive-compulsive disorder in females
      but not males.
AB  - A polymorphism in the coding region of catechol-O-methyltransferase gene (COMT)
      was previously reported to be associated with obsessive-compulsive disorder
      (OCD), particularly in male probands. We attempted to replicate the previous
      finding using a family-based genetic design in haplotype relative risk (HRR) and
      transmission disequilibrium (TDT) analyses. Fifty-six OCD probands and their
      parents were genotyped for the COMT locus using established methods. Analysis of
      allele and genotype frequencies between the proband genotypes and the control
      (parental nontransmitted) genotypes failed to replicate the previous finding of
      gender divergence, gave no evidence of overall association, nor was linkage
      detected by TDT. However, further analysis of the COMT allele frequencies by
      proband gender gave evidence of a mildly significant association with the low
      activity COMT allele in female probands (P=0.049), but not in male probands.
      These findings indicate that COMT may be etiologically relevant to OCD in a
      gender-specific manner opposite to that shown in previous studies.

PMID- 11840518
TI  - Lipoproteins modulate growth and differentiation of cultured human epidermal
      keratinocytes.
AB  - The effects of various lipoproteins on the growth and the differentiation of
      cultured normal human keratinocytes were investigated. Primary cultures of human
      epidermal keratinocytes were obtained from neonatal foreskin, and then added with
      lipoproteins, very low density lipoprotein (VLDL), low density lipoprotein (LDL),
      and high density lipoprotein (HDL). Cell growth potential was examined using the
      3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. VLDL
      and LDL enhanced keratinocytes growth and LDL receptor expression at the plasma
      membrane level. These effects were more remarkably observed in cells cultured
      with VLDL than in cells cultured with LDL. Apolipoprotein E (ApoE) was highly
      increased in VLDL treated cells. These results suggest that VLDL binds with high
      affinity to cell surface receptors and induces cell proliferation.

PMID- 11840519
TI  - The use of gel and capillary electrophoresis to investigate some of the
      fundamental physical properties of DNA.
AB  - Electrophoresis is a powerful technique which can be used not only for the size
      based separation of DNA in slab gels and sieving liquid polymers, but also for
      the analysis of sequence-dependent variations in DNA conformation and structure.
      Polyacrylamide gels are useful for conformational analysis, because bent or
      curved DNA molecules migrate anomalously slowly in this gel medium. Bending is
      often (but not always) associated with runs of adenine residues (A-tracts) that
      occur in phase with the helix repeat. The unique structure responsible for DNA
      bending "melts out" at a temperature considerably below that of strand
      separation. The circular permutation assay is another polyacrylamide gel-based
      method of detecting bending. It has usually been applied to small restriction
      fragments, but can also be used to detect bending in plasmid-sized DNA molecules.
      The apparent bends in plasmid DNAs tend to be located near biologically important
      regions of the sequence, such as the origin of replication, the start site of
      transcription, and the promoters of certain genes. Finally, capillary
      electrophoresis in free solution (without sieving liquid polymers) can be used to
      determine the diffusion coefficients of small DNA molecules, detect DNA-buffer
      interactions, and analyze the sequence dependence of counterion binding.
      Counterions appear to be preferentially bound to DNA oligomers containing A
      tracts, especially the A(n)T(n) sequence motif. Typical examples of these
      applications of gel and capillary electrophoresis to the study of DNA
      conformation and structure are described.

PMID- 11840520
TI  - Adaptive weighted least squares method for the estimation of DNA fragment lengths
      from agarose gels.
AB  - The size of DNA fragments is most frequently estimated from their electrophoretic
      mobilities. Agarose gels are used to estimate the size of DNA fragments ranging
      from a few hundred nucleotides to more than 20 kbp. The common practice when
      estimating the unknown fragment sizes is to plot the log of the size of molecular
      weight standards against their mobility and read the values of unknowns from this
      graph. However, due to perturbations in the gel, such plots often show pronounced
      curvature which may introduce significant subjectivity into the interpolation
      process. We present a new method "adaptive weighted least squares (AWLS)" based
      on the significance test to choose the order of polynomial. We compare this with
      the method introduced by Schaffer based on the modification of the Southern
      method. The results obtained by AWLS are significantly better than the method
      introduced by Schaffer. Different lanes are tested for consistency.

PMID- 11840521
TI  - Mean free path and peak dispersion in the geometration motion in gel
      electrophoresis.
AB  - The concept of the mean free path, i.e., the mean distance between subsequent
      collisions of DNA molecules with gel fibers, is introduced to the model
      description of the geometration effect. A new formula is derived for the
      correction to the velocity v of long molecules in gel due to the geometration
      process: v = v(r)/(1+3s/4b), where v(r) is the velocity without geometration, s
      is the molecule length and b is the mean free path of molecules. The peak
      dispersion sigma(x) is evaluated with the same model approach. We get the
      contribution to the bandwidth from the geometration effect. For b = s the
      bandwidth is about 2(sx)(1/2), where x is the length of the path of the molecules
      in gel. The results are compared with experimental data on the linearized plasmid
      pKecNOS in 4% agarose gel.

PMID- 11840522
TI  - Polymerase chain reaction-restriction fragment length polymorphism of ribosomal
      internal transcribed spacer region analysis on polyacrylamide gel electrophoresis
      reveals two haplotypes coexisting in Myzus persicae.
AB  - Aphids are geographically and economically the most important group of
      phytophagous insects. They are responsible for various damage on cultivated
      plants. In our laboratory, we are interested in their ability to transmit
      phytoviruses such as Rhabdovirus, Cucumovirus, Potyvirus, and Caulimavirus which
      cause many crop diseases. The present work deals with the study of vectors as
      analyzed by polymerase chain reaction-restriction fragment length polymorphism
      (PCR-RFLP) of internal transcribed spacer (ITS) regions. Electrophoresis of PCR
      RFLP products using EcoRV, AluI and DraI restriction enzymes on 10% polyacrylamid
      gel reveals the coexistence of two different haplotypes in the same individual
      genome. This result seems to explain some features of aphid evolution.

PMID- 11840523
TI  - Multiple advantages of capillary zone electrophoresis for exploring protein
      conformational stability.
AB  - This review summarizes the work of our laboratory to explore the use of capillary
      zone electrophoretic (CZE) methods for the investigation of protein
      conformational stability. Early CZE works on protein denaturation as well as
      fundamental and theoretical considerations are discussed. Instrumental aspects of
      the CE-based approach including general and particular CE requirements are
      documented. Several aspects dealing with estimation of stability of enzymes
      (cholinesterases and organophosphate-hydrolyzing enzymes) interacting with
      organophosphates profusely illustrate the multiple advantages of CZE. The
      discrimination of parameters controlling the "good compromise"
      stability/plasticity for allowing functional efficiency of these enzymes is
      exemplified. Thermal stability, susceptibility to high electric field, alteration
      of stability by bound ligands and the role of associated cations in
      metalloenzymes have been successfully investigated.

PMID- 11840524
TI  - Repartition effect of aromatic polyaniline coatings on the separation of
      bioactive peptides in capillary electrophoresis.
AB  - The capillary walls of fused-silica capillary electrophoresis (CE) columns were
      modified with a thin film of polyaniline (PANI), providing open-tubular columns
      with a stable coating containing aromatic groups and amine functionalities. Fast
      and efficient separations were observed for small bioactive peptides under acidic
      conditions on PANI-coated columns. The mechanism of separation is based on
      hydrophobic interactions between the analytes and the polymeric matrix. Good
      reproducibility was observed from run-to-run. Due to the simple derivatization
      procedure, method flexibility, the uniformity of the coating and its stability,
      conjugated polymers could find practical application in capillary zone
      electrophoresis (CZE) separations.

PMID- 11840525
TI  - Development of an integrated capillary electrophoresis/sensor for L-ascorbic acid
      detection.
AB  - A CE/biosensor for measuring ascorbic acid was developed by coupling a
      polyaniline optical sensor and capillary electrophoresis (CE). The capillary
      column was partially modified with a thin film of polyaniline redox sensitive
      material. Ascorbic acid was detected by monitoring the changes in optical
      absorbance occurring to the polyaniline film upon the reduction reaction. The
      sensor response (change in optical absorbance at 650 nm) is proportional to the
      concentration of ascorbic acid over a range of 2.5-250 mg/L and the response
      range has shown a clear dependence on the characteristics of the polymerized
      film. High specificity and sensitivity of the present method, low sample
      consumption, short times of response (ca. 2 min) and the reproducibility of the
      results demonstrate that the CE/polyaniline-sensor could be further employed in
      the study of the relation between the content of L-ascorbic acid in body fluids
      and clinical parameters, e.g., cell ageing.

PMID- 11840526
TI  - Analysis and characterization of phosphinic pseudopeptides by capillary zone
      electrophoresis.
AB  - Capillary zone electrophoresis (CZE) was applied to analysis and characterization
      of phosphinic pseudopeptides with the general structure N-Ac-Val-Ala(psi)(PO2(-)
      CH(2)) Leu-Xaa-NH(2), where Xaa represents one of 20 proteinogenic amino acid
      residues. Pseudopeptides containing neutral or acidic amino acid residues in
      position Xaa were analyzed as anions in weakly alkaline (pH 8.1) Tris-Tricine
      background electrolyte (BGE), pseudopeptides with basic amino acid residues in
      position Xaa were analyzed as cations in acid BGEs (Tris-phosphate buffers).
      Acidity of phosphinic acid moiety in peptides with basic amino acid residues was
      determined from the dependence of effective mobility of these peptides on pH in
      the acid pH region (pH 1.4-2.8). Additionally, separation of diastereomers of
      some peptides was achieved.

PMID- 11840527
TI  - Application of capillary zone electrophoresis to the screening of some
      angiotensin II receptor antagonists.
AB  - A capillary zone electrophoretic (CZE) method was optimized for the separation of
      five angiotensin II receptor antagonists (Losartan, Irbesartan, Valsartan,
      Telmisartan and Eprosartan) and two of their metabolites (EXP 3174 and
      Candesartan M1) by means of experimental design methodologies. The aim of this
      study was to define rapidly experimental conditions under which the analytes can
      be resolved for quantitation. The effects of the buffer (pH, concentration and
      composition), the organic modifier and voltage were studied. Critical factors
      were identified in a screening design (fractional factorial design) and
      sequentially an optimization design (central composite design) was used to choose
      optimal conditions for separation. The most favorable electrophoretic conditions
      were found by setting the resolution at a threshold value (Rs < or = 1.5) and
      minimizing, if possible, analysis time. Successful results were obtained with a
      50 mM potassium dihydrogen phosphate:boric acid (25:75 v/v) buffer at pH 5.5 in
      the presence of 5% methanol and application of a 25 kV voltage. Analysis time was
      8 min in a conventional fused-silica capillary (50 cm effective length) in a
      normal cationic mode (anode at the inlet and cathode at the outlet) after
      hydrostatical sample injection for 30 s.

PMID- 11840528
TI  - Separation of the high-ceiling diuretic Torasemide and its metabolites by
      capillary zone electrophoresis with diode-array detection.
AB  - A capillary zone electrophoretic method was developed for the separation of the
      high-ceiling loop diuretic Torasemide and three of its metabolites (M1, M3 and
      M5) using an experimental design approach. Two different experimental designs
      were employed to optimize the developed method: (i) a fractional factorial design
      examining six factors at two levels (2(6-2)) and (ii) a central composite design
      examining two factors at two levels (2(2)+2x2+p). The factors studied were: pH,
      buffer concentration, proportion of boric acid in the mixed boric acid:potassium
      dihydrogen phosphate background electrolyte, temperature, applied voltage and
      percentage of organic modifier. Resolution between peaks was established as
      response. Separation of the four studied compounds was achieved in less than 8
      min, using an electrolyte of 20 mM boric acid:potassium dihydrogen phosphate
      (75:25 v/v) with 15% MeOH adjusted to pH 9.7 with KOH, at a potential of 28 kV.
      Detection wavelength and temperature were 206 nm and 35 degrees C, respectively.

PMID- 11840529
TI  - Capillary electrochromatographic study of sapphyrin-organophosphoric acid
      derivatives interaction.
AB  - Interaction of phosphate moiety possessing compounds with sapphyrin was studied
      using open-tubular electrochromatography in sapphyrin-coated capillaries. It was
      revealed that phenylthiohydantoin (PTH)-phosphoserine and PTH-phosphothreonine
      exert such a strong interaction that they can not be eluted from the sapphyrin
      coated capillary even at prolonged run times (70 min). Nucleoside polyphosphates
      show generally strong interaction (but weaker than the above mentioned serine and
      threonine derivatives) no matter whether they possess one or two bases. Also the
      number of phosphate residues present in nucleoside polyphosphates tested plays a
      secondary role only. p-Aminobenzylphosphoric (p-ABPA) acid exhibited an
      unexpected behavior. It was retained more in the phosphate containing buffer than
      in borate-acetate. This appears to indicate that other than complexing of the
      phosphate moiety may be involved in the interaction. As no such effects were
      observed with the PTH-derivatives of serine and threonine it was concluded that
      additional interaction (if involved) depends on the nature of the organic part of
      the molecule.

PMID- 11840530
TI  - Study of perrhenate reduction by capillary electrophoresis.
AB  - The influence of perrhenate concentration, the concentration of the reducing
      agent and pH of the reaction mixture on the yield of perrhenate reduction were
      studied to find a possibility to decrease the stannous chloride concentration in
      the reaction mixture without negative changes on the yield of perrhenate
      reduction. Britton-Robinson buffer solutions were selected as the background
      electrolytes because of their buffering capacity in a wide pH interval. The
      highest degree of perrhenate reduction was obtained at pH 2 at perrhenate
      concentrations ranging from 10(-4) to 10(-3) mol/L. The stability of reduced
      rhenium against pH change from 2 to 5.5 and against dilution of rhenium in the
      reaction mixture to the concentration suitable for the application in
      radiotherapy were studied as well. The results obtained by capillary
      electrophoresis and by thin-layer chromatography with radiometric detection were
      compared.

PMID- 11840531
TI  - Analysis of artichoke (Cynara cardunculus L.) extract by means of micellar
      electrokinetic capillary chromatography.
AB  - The main constituents of artichoke extract were separated by micellar
      electrokinetic chromatography (MEKC), using a buffer consisting of 100 mM sodium
      dodecyl sulfate (SDS) in 20 mM sodium dihydrogen phosphate, 20 mM disodium
      tetraborate (pH 8.6) as background electrolyte. Optimum separation voltage of 28
      kV (positive polarity) and a capillary temperature of 25 degrees C gave the best
      analysis. The UV detection was performed at 200 nm. The method was successfully
      used to analyze plant and drug samples as well as for the study of artichoke
      antioxidant activity. The quantitative MEKC results were in good agreement to
      those obtained previously by reversed-phase high-performance liquid
      chromatography (RP-HPLC).

PMID- 11840532
TI  - Determination of lignans in Schisandra chinensis using micellar electrokinetic
      capillary chromatography.
AB  - Micellar electrokinetic capillary chromatography (MEKC) has been developed as a
      promising method for the determination of lignans in plant samples. The
      separation conditions have been optimized with respect to the different
      parameters including sodium dodecyl sulfate (SDS) and acetonitrile concentration,
      pH of the background electrolyte, separation voltage, and capillary temperature.
      The background electrolyte consisting of 40 mM SDS and 35% acetonitrile in 10 mM
      tetraborate buffer (pH 9.3) was found to be the most suitable electrolyte for
      this analysis. The applied voltage of 28 kV (positive polarity) and the capillary
      temperature 25 degrees C gave the best separation of lignans. The interday
      reproducibility of the peak areas and the migration times was below 2.0%. The
      results of MEKC analyses were compared with those obtained by capillary
      electrochromatography (CEC) and reversed-phase high-performance liquid
      chromatography (RP-HPLC). The possibilities of using this method for the
      determination of lignans in drug and in serum samples were also tested.

PMID- 11840533
TI  - Electrophoretic behavior of adamantane derivatives possessing antiviral activity
      and their determination by capillary zone electrophoresis with indirect
      detection.
AB  - Separation and determination of adamantane derivatives with antiviral activity,
      namely amantadine (1-adamantan amine), memantine (1-amino-3,5-dimethyl
      adamantane) and rimantadine (alpha-methyl-1-adamantane methylamine), were
      examined by capillary zone electrophoresis. After optimization, an indirect
      detection method using 5 mM 4-methylbenzylamine in ethanol/water solution (1:4)
      as simultaneously absorbing and buffering background electrolyte with detection
      at 210 nm was found suitable for determination of the individual compounds (limit
      of detection was 0.35 mg L(-1) for memantine hydrochloride, S/N = 3). Baseline
      separation of all the three compounds was reached by addition of alpha- or beta
      cyclodextrins to the electrolyte in concentrations of 20 and 2 mM, respectively.

PMID- 11840534
TI  - Simultaneous determination of trans-resveratrol and sorbic acid in wine by
      capillary zone electrophoresis.
AB  - A method for separation and determination of sorbic acid, a food and beverage
      preservative, and trans-resveratrol, a biomedically active substance, in wine by
      capillary zone electrophoresis is described. A solid-phase extraction step on C18
      column prior to the electrophoretic separation providing lower detection limits
      was used for trans-resveratrol determination. For determination of sorbic acid
      direct analysis of wine (without a preconcentration step) was used. The method is
      rapid and sensitive and was applied to the analysis of wines from Alsace, France.

PMID- 11840535
TI  - Capillary zone electrophoresis of humic acids from the American continent.
AB  - A multicomponent background electrolyte (BGE) was developed and its composition
      optimized using artificial neural networks (ANN). The optimal BGE composition was
      found to be 90 mM boric acid, 115 mM Tris, and 0.75 mM EDTA (pH 8.4). A
      separation voltage of 20 kV, 20 degrees C and detection at 210 nm were used. The
      method was applied to characterize several humic acids originating from various
      countries of the American continent: soil (Argentina), peat (Brazil), leonardite
      (Guatemala and Mexico) and coal (United States). Comparison with humic acids of
      International Humic Substances Society (IHSS) standard samples was also done.
      Well reproducible electropherograms showing a relatively high number of peaks
      were obtained. Characterization of the samples by elemental analysis and UV
      spectrophotometry was also done. In spite of the very different origins, the
      similarities between humic acids are high and by matrix assisted
      desorption/ionization-time of flight (MALDI-TOF)-mass spectrometry it was shown
      that most of the m/z patterns are the same in all humic acids. This means that
      humic acids of different origin have the same structural units or that they
      contain the same components.

PMID- 11840536
TI  - Dermal nitrate: an old marker of firearm discharge revisited with capillary
      electrophoresis.
AB  - The present work describes a capillary electrophoretic method for nitrite and
      nitrate determination to be used as a screening tool for investigating the
      residues of firearm discharge. The use of capillary electrophoresis allowed the
      rapid determination of nitrite and nitrate, which are major inorganic components
      of gunshot residues, offering a quantitative and selective alternative to the
      traditional paraffin test (dermal nitrate test). The method is simpler, cheaper,
      and faster than the modern approaches to gunshot residue analysis based on the
      determination of barium, lead and antimony by using flameless absorption
      spectrometry, inductively coupled plasma-mass spectrometry (ICP-MS), or scanning
      electron microscopy. The analysis was carried out in a bare fused-silica
      capillary (75 microm inner diameter) with a 100 mM borate buffer (pH 9.24). The
      detection was by UV absorption at 214 nm. Separation took place under reversed
      voltage of 15 kV. Bromide was used as the internal standard. Sensitivity was
      about 1 mM for both nitrite and nitrate. Reproducibility (intraday and day-to
      day) was also good with relative standard deviations (RSDs) < 1.0% for relative
      migration times and < 4.5% for peak areas in both standard solutions and real
      matrix. Hair and skin samples from a victim shot in the head were successfully
      analyzed for the presence of nitrite and nitrate.

PMID- 11840537
TI  - Spot overlapping in two-dimensional polyacrylamide gel electrophoresis
      separations: a statistical study of complex protein maps.
AB  - A statistical approach able to extract the information contained in a two
      dimenisional polyacrylamide gel electrophoresis (2-D PAGE) separation is here
      reported. The method is based on the quantitative theory of peak overlapping, a
      procedure previously developed by the authors and here extended to 2-D
      separations. The whole map is divided into many strips in order to obtain 1-D
      separations on which the statistic procedure is applied: the developed
      algorithms, on the basis of spot experimental data (intensity and spatial
      coordinates) permit to estimate the intrinsic number of components and to single
      out the specific order present in spot positions. The procedure was validated on
      computer-simulated maps. Its applicability to real samples was tested on maps
      obtained from literature sources. The following important information on protein
      mixtures can be extracted: (i) the number of proteins can be accurately
      estimated, on the basis of the spatial coordinates and intensities of spots
      detected in the 2-D PAGE map; (ii) the model describing distribution of
      interdistance between adjacent spots can be identified in both the separation
      dimensions; (iii) the presence of repeated interdistances in spot positions in
      the maps can be easily singled out: these regularities suggest specific protein
      modifications.

PMID- 11840538
TI  - Two-dimensional maps in soft immobilized pH gradient gels: a new approach to the
      proteome of the Third Millennium.
AB  - Same major improvements in proteome analysis of cytosolic and membrane proteins
      by two-dimensional mapping are here reported. A much improved transfer of
      proteins from the first to the second dimensional sodium dodecyl sulfate (SDS)
      gel is obtained by simply diluting the gel matrix, normally composed of 4%T
      polyacrylamide in all commercially available Immobiline strips down to as low as
      3%T. In the analysis of total lysates of platelets, this augmented transfer has
      been evaluated as being 2-3 times higher than in standard 4%T gels. A second
      major improvement, in the case of analysis of membrane protein preparations, has
      been demonstrated to consist in a delipidation step in a tertiary solvent mixture
      composed of tri-n-butyl phosphate:acetone:methanol in a 1:12:1 ratio. By adopting
      this protocol, large amounts of spectrins (240-220 kDa, filamentous proteins of
      the red blood cell membranes) could be transferred vs. essentially none when
      delipidation was omitted. The present report also confirms the importance of a
      reduction and alkylation step of the protein sample prior to all electrophoretic
      steps, including focusing in the Immobiline gel, as recently reported by Herbert
      et al.

PMID- 11840539
TI  - Proteome analysis of rat polymorphonuclear leukocytes: a two-dimensional
      electrophoresis/mass spectrometry approach.
AB  - The development of a two-dimensional (2-D) map of rat polymorphonuclear (PMN)
      leukocytes is here reported for the first time. The map is built up by utilizing
      a wide immobilized pH gradient (IPG), pH 3-10, in the first dimension and also a
      narrower IPG pH 4.5-8.5 gradient. In addition, the map is constructed by adopting
      the most recent protocols in 2-D mapping, which call for reduction and alkylation
      of the sample prior to the start of any electrophoretic step, including the IPG
      dimension. Fifty-two major protein spots have been so far identified by utilizing
      both matrix assisted laser desorption/ionization-time of flight (MALDI-TOF) and
      electrospray quadrupole (Q)-TOF mass spectrometry. A large number of house
      keeping and cytoskeleton proteins were detected, together with proteins which are
      specific to PMN organelles or related to PMN functions such as phagocytosis and
      chemotaxis. The results obtained demonstrate the possibility of obtaining a
      single 2-D gel based proteomic map of PMN with representative proteins from
      different cellular compartments, also including membrane components, allowing the
      study of PMN protein expression on a proteome-wide scale. The aim of this project
      is to build an extensive database of such proteins, to be utilized for future
      studies where the expression of PMN proteins is used as a disease- or drug
      treatment marker.

PMID- 11840540
TI  - The rat liver mitochondrial proteins.
AB  - Subcellular fractionation increases the probability of detection of low-abundance
      proteins. We prepared a fraction highly enriched in mitochondrial proteins from
      rat liver. The proteins were analyzed by two-dimensional (2-D) electrophoresis
      using broad-and narrow-range immobilized pH gradient strips, and identified by
      matrix assisted laser desorption/ionization-mass spectrometry (MALDI-MS). 192
      different gene products were detected, of which approximately 70% were enzymes
      with a broad spectrum of catalytic activities. Most of the identified proteins
      were detected in other rat protein samples as well, which were analyzed in our
      laboratory. Eight gene products were detected for the first time. These were
      represented by one spot each, whereas most of the frequently detected proteins
      were represented by multiple spots. In average, approximately 10-15 spots
      corresponded to one gene product.

PMID- 11840541
TI  - Electrophoretic analysis of phosphorylation of the yeast 20S proteasome.
AB  - The 26S proteasome complex, consisting of two multisubunit complexes, a 20S
      proteasome and a pair of 19S regulatory particles, plays a major role in the
      nonlysosomal degradation of intracellular proteins. The 20S proteasome was
      purified from yeast and separated by two-dimensional gel electrophoresis (2-DE).
      A total of 18 spots separated by 2-DE were identified as the 20S proteasome
      subunits by peptide mass fingerprinting with matrix assisted laser
      desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS). The alpha2
      , alpha4- and alpha7-subunits gave multiple spots, which converged into one spot
      for each subunit when treated with alkaline phosphatase. The difference of pI
      between phosphorylated and dephosphorylated spots and their reaction against anti
      phosphotyrosine antibody suggested that the alpha2- and alpha4-subunits are
      phosphorylated either at Ser or at Thr residue, and the alpha7-subunit is
      phosphorylated at Tyr residue(s). These phosphorylated subunits were analyzed by
      electrospray ionization-quadrupole time of flight-tandem MS (ESI-QTOF-MS/MS) to
      deduce the phosphorylation sites. The 20S proteasome has three different protease
      activities: chymotrypsin-like, trypsin-like and peptidylglutamyl peptide
      hydrolyzing activities. The phosphatase treatment increased K(m) value for
      chymotrypsin-like activity of the 20S proteasome, indicating that phosphorylation
      may play an important role in regulating the proteasome activity.

PMID- 11840542
TI  - Comparative two-dimensional mapping of prion protein isoforms in human
      cerebrospinal fluid and central nervous system.
AB  - The cellular prion protein (PrP(C)) is a glycosylphosphatidylinositol (GPI)
      anchored glycoprotein abundant in neurons. Although its precise function is
      unknown, PrP(C) represents the substrate for the generation of a conformational
      pathogenic isoform (PrP(Sc)) in human and animal transmissible spongiform
      encephalopathies, or prion diseases. By applying novel solubilization cocktails,
      we analyzed normal human brain and cerebrospinal fluid (CSF) PrP(C) by immunoblot
      of two-dimensional (2-D) gel electrophoresis preparations, using specific
      antibodies. Here, we show that PrP(C) from brain and CSF is composed of several
      charge isomers of differently glycosylated isoforms of the full-length PrP(C) and
      two N-terminally truncated fragments of 20 and 18 kDa. In the CSF, substantial
      amounts of the highly glycosylated PrP(C) isoforms and of the unglycosylated 18
      kDa fragment are detected. Our study, for the first time, provides a detailed 2-D
      map of human PrP(C) both in brain and CSF, and establishes an innovative and
      sensitive method that might help in detecting the CSF pathological PrP(Sc)
      isoform in vivo. It also shows the incredible microheterogeneity of such isoforms
      (ca. 60 spots!), as revealed in 2-D mapping, as opposed to 3-4 main zones by mono
      dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE).

PMID- 11840543
TI  - Two-dimensional mapping of three phenotype-associated isoforms of the prion
      protein in sporadic Creutzfeldt-Jakob disease.
AB  - Transmissible spongiform encephalopathies (TSE), or prion diseases, are mammalian
      neurodegenerative disorders characterized by a conformational modification of the
      host-encoded prion protein (PrP(C)) into an isoform which is detergent-insoluble
      and partially resistant to protease treatment (PrP(Sc)). Distinct types of
      PrP(Sc), differing in conformation and variation in the relative amount of their
      glycoforms, have been associated with different phenotypes of TSE. In sporadic
      Creutzfeldt-Jakob disease (sCJD), two major types of PrP(Sc), with proteinase K
      (PK)-resistant fragments of 21 and 19 kDa, have been described. No consensus
      exists, however, on the molecular classification of PrP(Sc) in sCJD, since
      further heterogeneity within PrPSc conformers has been reported. We studied 19
      subjects with dementia or dementia/ataxia at onset and 12 subjects with ataxia at
      onset. Following two-dimensional gel electrophoresis, we characterized PrP(C) and
      PrP(Sc) species in normal and sCJD brains by immunoblotting with antibodies
      recognizing N-terminal and C-terminal PrP regions. Three types of PrP(Sc) were
      detected in detergent-insoluble fractions from sCJD brains, mainly consisting of
      full-length PrP(Sc) in subjects with rapidly progressive dementia, and two
      different sets of amino-truncated PrP(Sc) glycoforms in subjects with
      dementia/ataxia and ataxia at onset. Examination of the PrP(Sc) core fragment,
      following PK treatment and deglycosylation, confirmed the existence of three
      distinctive patterns. These findings have immediate implications for the
      molecular classification of sCJD.

PMID- 11840544
TI  - Proteomics and immunomapping of reactive lymph-node and lymphoma.
AB  - In the present study we show that two-dimensional (2-D) maps together with immuno
      detection allow the precise identification of important leukocyte differentiation
      and tumor markers (e.g., CD3 and CD5), and important cell cycle regulatory
      molecules such as cyclin dependent kinases, notably CDK6. In addition, the
      comparative evaluation of molecular expression (e.g., CD5) in maps developed with
      normal and lymphoma samples can provide reproducible and precise information
      regarding the molecular expression in different cell populations. Accordingly, we
      could detect a much increased level of expression of CD5 in mantle cell lymphoma,
      up to ten times higher than in the control. In addition, CD5 in tumor tissues
      seems to be microheterogeneous as compared to normal samples.

PMID- 11840547
TI  - Tricarboxylic acid cycle of glia in the in vivo human brain.
AB  - In the brain, acetate is exclusively oxidized by glia. To determine the
      contribution of glial metabolism to the tricarboxylic acid cycle (TCA), 1-(13)C
      acetate was infused in six studies in three normal adult subjects and -one
      epileptic receiving valproic acid for seizure control. Ten grams of 99% 1-(13)C
      labeled acetate were infused intravenously as a 3.3% w/v solution over 60 min,
      during which in vivo 13C MR spectra of the brain were acquired. As expected, 13C
      label rapidly enriched cerebral bicarbonate, glutamate and glutamine C5. The mean
      rate of acetate oxidation calculated from steady-state 13C enrichment of
      bicarbonate in fasted normal subjects was 0.13 +/- 0.03 micromol/g/min (n=4),
      approximately 20% of the total cerebral TCA cycle rate.

PMID- 11840548
TI  - Monitoring cytotoxic tumour treatment response by diffusion magnetic resonance
      imaging and proton spectroscopy.
AB  - Exposure of tumours to anti-cancer drugs, gene or radiation therapy consistently
      leads to an increase in water diffusion in the cases expressing favourable
      treatment response. The diffusion change coincides cytotoxic cell eradication and
      precedes volume reduction in drug or gene therapy-treated experimental tumours.
      Interestingly, the recent studies from human brain tumour patients undergoing
      chemotherapy show similar behaviour of diffusion, suggesting important
      application for MRI in patient management. In this review observations from
      diffusion MRI and MRS in the tumours during cytotoxic treatment are summarized
      and the cellular mechanisms affecting molecular mobility are discussed in the
      light of tissue microenvironmental and microdynamic changes.

PMID- 11840549
TI  - Phosphorus-31 MR spectroscopy of normal adult human brain and brain tumours.
AB  - Localized phosphorus-31 MR spectra were obtained in vivo in a large series of
      normal human brain tissue specimens of healthy volunteers (n=36) and various
      brain tumours (n=52). Tumour types examined included grade II and grade III
      gliomas (n=15 and n=1, respectively), glioblastomas (n=16) and meningeomas
      (n=12). An additional eight tumours were analysed during chemo- or radiotherapy.
      Spectra were acquired using a modified ISIS pulse sequence with a repetition time
      of 3 s. Voxel sizes ranged from 56 to 129 ml. The spectra were evaluated using a
      least-square variable projection (VARPRO) fitting procedure in the time domain,
      which allows semi-quantitative determination of relative metabolite
      concentrations. The measurements in normal cerebrum of healthy volunteers
      revealed the following results of metabolite signal intensity ratios: pH 7.04 (+/
      0.01), PCr/alpha-ATP 0.51 (+/- 0.03), P(i)/alpha-ATP 0.17 (+/-0.02), PCr/P(i)
      2.09 (+/-0.12), PDE/alpha-ATP 3.65 (+/-0.13) and PME/alpha-ATP 0.41 (+/-0.04).
      Meningiomas showed the most obvious changes when compared with normal brain
      tissue. They are characterized by an alkaline environment (pH 7.16 +/- 0.03;
      p<0.005), a decrease in the phosphocreatine peak (p<0.0001) and significantly
      decreased phosphodiesters (p<0.0001). Glioblastomas also showed alkalization (pH
      7.12 +/- 0.02; p<0.001) and a decrease in PDE/alpha-NTP (p<0.05), but no
      significant changes in PCr/alpha-NTP or PCr/Pi. In gliomas with low malignancy,
      less distinct changes could be detected with slight alkalization (pH 7.09 +/-
      0.02; p<0.05) and more than a two-fold reduction in the PDE/alpha-NTP ratio
      (p<0.05). The spectra of brain tumours during chemo- and radiotherapy indicated
      clear but inconsistent influence of the therapy.

PMID- 11840550
TI  - Spectrally inhomogeneous BOLD contrast changes detected in rodent tumors with
      high spectral and spatial resolution MRI.
AB  - MRI detects changes in blood-oxygenation-level dependent (BOLD) contrast in
      tumors caused by tumor oxygenating agents. These changes can be used to guide the
      design of improved tumor oxygenating treatments (TOXs). The conventional approach
      to detection of BOLD effects assumes that the water resonance is a single,
      homogeneously broadened Lorentzian line, and that changes in the T2* of this line
      owing to changes in deoxyhemoglobin are spectrally homogeneous. This model may
      not adequately describe BOLD contrast changes in complex water resonances that
      are often detected in tumors. The present work investigated: (a) whether changes
      in the water resonance in very small voxels caused by tumor oxygenating agents
      are spectrally inhomogeneous; and (b) whether high spectral and spatial
      resolution (HiSS) MRI of the water and fat resonances detects these changes more
      accurately than conventional gradient-recalled echo (GRE) imaging. Carbogen (95%
      oxygen, 5% CO2) was used to increase tumor oxygenation. In two tumor models
      [mammary adenocarcinoma (R3230Ac; n=5) and rhabdomyosarcoma (BA1112; n=5)] proton
      signals were often complex and inhomogeneously broadened. Spectrally
      inhomogeneous changes during carbogen breathing occurred in at least 10% of the
      R3230AC tumor voxels that responded to carbogen and 18% of BA1112 tumor voxels.
      The largest changes during carbogen breathing in many voxels occurred at
      frequencies that were significantly different from the frequency of the primary
      water peak. Carbogen-induced changes in proton T2* detected by simulated GRE and
      HiSS differed by more than 75% in 67% of voxels in R3230Ac tumors and in 65% of
      voxels in BA1112 tumors. The spectrally inhomogeneous effects of tumor
      oxygenating agents may reflect changes in sub-voxelar microenvironements and thus
      may be important for accurate evaluation of the effects of therapy.

PMID- 11840551
TI  - A comparison of cell and tissue extraction techniques using high-resolution 1H
      NMR spectroscopy.
AB  - Analysis of brain metabolites by a wide range of analytical techniques is
      typically achieved using biochemical extraction methodologies that require either
      two separate samples or two separate extraction steps to prepare both aqueous and
      organic metabolite fractions. However there are a number of brain pathologies in
      which both aqueous metabolite and lipid changes occur so that a simultaneous
      extraction of both fractions would be valuable. The methanol-chloroform (M/C)
      technique enables extraction of both aqueous metabolites and lipids
      simultaneously. It is already well established for lipid extraction of cells and
      tissue but its efficiency and reproducibility for extraction of aqueous
      metabolites is unknown. Therefore, we compared the aqueous metabolite yield and
      the reproducibility of the M/C method to the commonly used perchloric acid (PCA)
      method, using 1H-NMR spectroscopy of adult rat brain and purified rat astrocyte
      culture extracts. The results indicate that M/C is a superior technique for
      aqueous metabolite extraction from both brain tissue and cells when compared to
      the PCA method. The M/C extraction technique enables the simultaneous extraction
      of both lipids and aqueous metabolites from a single sample using small solvent
      volumes, making it well suited for NMR investigations of both tissues and cells.

PMID- 11840552
TI  - Hepatic gluconeogenesis and Krebs cycle fluxes in a CCl4 model of acute liver
      failure.
AB  - Acute liver failure was induced in rats by CCl4 administration and its effects on
      the hepatic Krebs cycle and gluconeogenic fluxes were evaluated in situ by 13C
      NMR isotopomer analysis of hepatic glucose following infusion of [U
      13C]propionate. In fed animals, CCl4 injury caused a significant increase in
      relative gluconeogenic flux from 0.80+/-0.10 to 1.34 +/-0.24 times the flux
      through citrate synthase (p<0.01). In 24-h fasted animals, CCl4-injury also
      significantly increased relative gluconeogenic flux from 1.36+/-0.16 to 1.80+/
      0.22 times the flux through citrate synthase (p<0.01). Recycling of PEP via
      pyruvate and oxaloacetate was extensive under all conditions and was not
      significantly altered by CCl4 injury. CCl4 injury significantly reduced hepatic
      glucose output by 26% (42.8+/-7.3 vs 58.1+/-2.4 micromol/kg/min, p=0.005), which
      was attributed to a 26% decrease in absolute gluconeogenic flux from PEP (85.6+/
      14.6 vs 116+/-4.8 micromol/kg/min, p<0.01). These changes were accompanied by a
      47% reduction in absolute citrate synthase flux (90.6+/-8.0 to 47.6+/-8.0
      micromol/kg/min, p<0.005), indicating that oxidative Krebs cycle flux was more
      susceptible to CCl4 injury. The reduction in absolute fluxes indicate a
      significant loss of hepatic metabolic capacity, while the significant increases
      in relative gluconeogenic fluxes suggest a reorganization of metabolic activity
      towards preserving hepatic glucose output.

PMID- 11840553
TI  - PCr overshoot': a study of the duration in canine myocardium.
AB  - The phosphocreatine (PCr) overshoot is a well-documented phenomenon and is
      readily observable by 31P MRS. In addition, a second 31P MRS observation during
      ischemia with reperfusion is a diminution in ATP levels. Combining these two as
      the 'PCr Overshoot' the PCr/ATP ratio may provide an index of viability. However
      little information is available regarding the duration of this 'overshoot'. For
      this approach to be useful clinically, the duration of this phenomenon must be
      ascertained. An open chest canine model of 12 min of ischemia followed by
      reperfusion (6h) was used. A 2 cm surface coil was sutured to the myocardium and
      spectra were acquired at 4.7 T. Gated spectra were acquired in <2.5 min with an
      interpulse delay of 5 s. Integrals of the PCr and ATP (beta) resonances were
      analyzed using a line-fitting routine. Overall, the PCr signal increased from
      22.0+/-0.8 to 25.5+/-0.9 and ATP decreased from 11.7+/-0.4 to 10.0+/-0.4
      (arbitrary units). The PCr remained elevated for the entire 6h period and the
      percentage increase was 15.9%. The ATP remained depleted for the entire 6h period
      and the percentage decrease was 17.0%. Thus, the clinically relevant and readily
      observable PCr/ATP is a product of both an increase in PCr and a decrease in ATP
      for a calculated net increase in PCr/ATP of 39.6%. The PCr/ATP ratio of the
      ischemia group for baseline, ischemia, 6h reflow, were: 2.33+/-0.18, 1.04+/-0.29
      and 3.22+/-0.21. We demonstrate that the 'PCr overshoot' is readily observable
      and can be monitored noninvasively and nondestructively for 6h. Therefore, the
      'PCr overshoot' may be a viable marker of reversible injury in this model and may
      prove to be applicable for detecting myocardial viability in patients.

PMID- 11840554
TI  - 31P NMR spectroscopy of blood plasma: determination and quantification of
      phospholipid classes in patients with renal cell carcinoma.
AB  - Advanced renal cell carcinoma (RCC) has a poor prognosis and is characterized by
      an unpredictable clinical course. The aim of this study was to assess the
      systemic phospholipid distribution as a possible marker of tumor stage and tumor
      spread beyond the kidney. To this end, the effect of renal cell carcinoma (RCC)
      on phospholipid concentrations in blood plasma using 31P NMR spectroscopy was
      studied in: (a) 29 patients with RCC prior to nephrectomy; (b) 19 healthy
      volunteers; (c) three patients with other renal tumors (renal metastases of
      bronchial carcinoma and of renal pelvic carcinoma, and a benign renal tumor).
      Furthermore, the phospholipid concentrations of eight patients of group (a) were
      determined 6 months after nephrectomy, when they were in remission. We found
      considerable deviations in the concentrations of the lysophosphatidylcholines
      (LPC1, LPC2) in both male and female patients with RCC compared to healthy
      volunteers (male--LPC1 0.217+/-0.062 vs 0.297+/-0.049 mmol/l, LPC2 0.036+/-0.014
      vs 0.068+/-0.024 mmol/l; female--LPC1 0.195+/-0.071 vs 0.296+/-0.044 mmol/l, LPC2
      0.037+/-0.027 vs 0.044+/-0.014 mmol/l). In addition, female patients with RCC
      showed lower concentrations of phosphatidylcholines (PC; 1.409+/-0.268 vs 1.947+/
      0.259 mmol/l). The low phospholipid concentrations normalized for patients in
      remission. Phospholipid concentrations were found to depend on tumor stage and
      metastatic spread. The deviations in phospholipid concentrations (LPC1, LPC2, PC)
      observed may be attributable to systemic effects caused by the tumor as well as
      changes in enzyme activities.

PMID- 11840556
TI  - Current awareness.

PMID- 11840555
TI  - Diffusion-weighted in vivo localized proton MR spectroscopy of human cerebral
      ischemia and tumor.
AB  - The apparent diffusion coefficients (ADCs) of water and brain metabolites were
      determined by proton MR spectroscopy on a clinical MR scanner for healthy
      volunteers and for pathological changes in cases of acute cerebral infarction and
      brain tumor. The ADCs of N-acetyl aspartate (NAA) and creatines in tissue
      involved in acute infarction were decreased compared to normal control values,
      while in tumors they showed increased values. Since NAA is a neuronal marker,
      these findings suggest that neuronal cell viscosity changes according to the
      pathological status of the tissue. The lactate ADC was significantly larger than
      the values for other major metabolites in cases of ischemia and tumor, suggesting
      that lactate is present in a different compartment. These results indicate that
      metabolite diffusion data can be used to reveal changes in the intracellular
      environment depending on the pathological status.

PMID- 11840558
TI  - Preparative two-dimensional gel electrophoresis at alkaline pH using narrow range
      immobilized pH gradients.
AB  - A reproducible high-resolution protein separation method is the basis for a
      successful differential proteome analysis. Of the techniques currently available,
      two-dimensional gel electrophoresis is most widely used, because of its
      robustness under various experimental conditions. With the introduction of narrow
      range immobilized pH gradient (IPG) strips (also referred to as ultra-zoom gels)
      in the first dimension, the depth of analysis, i.e. the number of proteins that
      can be resolved, has increased substantially. However, for poorly understood
      reasons isoelectric focusing on ultra-zoom gels in the alkaline region above pH 7
      has suffered from problems with resolution and reproducibility. To tackle these
      difficulties we have optimized the separation of semipreparative amounts of
      proteins on alkaline IPG strips by focusing on two important phenomena:
      counteracting water transport during isoelectric focusing and migration of
      dithiothreitol (DTT) in alkaline pH gradients. The first problem was alleviated
      by the addition of glycerol and isopropanol to the focusing medium, leading to a
      significant improvement in the resolution above pH 7. Even better results were
      obtained by the introduction of excess of the reducing agent DTT at the cathode.
      With these adaptations together with an optimized composition of the IPG strip,
      separation efficiency in the pH 6.2-8.2 range is now comparable to the widely
      used acidic ultra-zoom gels. We further demonstrated the usefulness of these
      modifications up to pH 9.5, although further improvements are still needed in
      that range. Thus, by extending the range covered by conventional ultra-zoom gels,
      the depth of analysis of two-dimensional gel electrophoresis can be significantly
      increased, underlining the importance of this method in differential proteomics.

PMID- 11840559
TI  - Development of improved cell lysis, solubilization and imaging approaches for
      proteomic analyses.
AB  - Analysis of complex biochemical processes at the level of the proteome requires
      methods that quantitatively solubilize cytosolic and membrane bound proteins yet
      are compatible with isoelectric focusing and sodium dodecyl sulfate
      polyacrylamide gel electrophoresis. In addition, it is often necessary to employ
      several highly sensitive detection methods to identify key proteins that are
      modified or exhibit a change in expression levels in response to a given
      experimental stimulus or condition. Methods were developed that efficiently
      extract tissues or lyse cultured cells and quantitatively solubilize proteins in
      a single step without the need to shear nucleic acids. These approaches utilize
      urea, thiourea, a mixture of detergents, low levels of an ampholyte blend,
      reductant and a combination of alcohols. To aid in the detection of low abundance
      proteins and the accurate identification of specific proteins of interest in
      these samples, two approaches were pursued. In one, proteins are transferred from
      two-dimensional (2-D) gels to blot membranes. Proteins are then detected by
      staining with SYPRO Ruby and the resulting 2-D protein pattern is captured using
      a charge-coupled device (CCD) camera. The blots are then probed with antibodies
      directed against the protein(s) or functionalities of interest. The resulting
      chemiluminescent blot image is also generated with the CCD camera and the
      fluorescent SYPRO Ruby image is recaptured again without moving the membrane. It
      is thereby possible to generate a direct image overlay of the blot pattern on
      that of the stained protein pattern. This approach significantly aids in the
      accurate identification of the dye-stained protein that is detected by the
      specific antibody. In addition to detecting protein post-gel transfer, a second
      approach utilizes protein samples labeled with fluorescent dyes prior to 2-D
      electrophoresis in an effort to increase the sensitivity of protein detection and
      to facilitate protein quantitation. It is also possible to stain the blots with
      different dyes and overlay these images as well. Using these approaches, it is
      possible to perform more rapid and accurate comparative analyses and proteomic,
      post-gel characterization of proteins of interest than using comparative image
      analysis of multiple gels.

PMID- 11840560
TI  - Multiwell in-gel protein digestion and microscale sample preparation for protein
      identification by mass spectrometry.
AB  - In-gel peptide digestion has become a widely used technique for characterizing
      proteins resolved by two-dimensional gel electrophoresis. Peptides generated from
      gel pieces are frequently contaminated with detergent and salts. Prior to matrix
      assisted laser desorption/ionization-time of flight mass spectrometry analysis,
      these contaminants are removed using micro scale C18 sample preparation columns.
      In this paper, data are presented to demonstrate the application of a solvent
      resistant MultiScreen 96-well plate with a low peptide binding membrane and
      ZipTip micropipette based sample preparation. Recoveries of peptides (m/z of 1000
      to 5000 Da) derived from standard protein protease digests, were estimated at
      various stages of the analytical process. An optimized protocol has been
      established and all the reagents and consumables have been packaged in a ready to
      use commercial kit. Data will be presented to show the application of this
      technology package to accelerate the throughput of protein characterization by
      protease fragmentation.

PMID- 11840561
TI  - Protein purification by Off-Gel electrophoresis.
AB  - A novel free-flow protein purification technique based on isoelectric
      electrophoresis is presented, where the proteins are purified in solution without
      the need of carrier ampholytes. The gist of the method is to flow protein
      solutions under an immobilised pH gradient gel (IPG) through which an electric
      field is applied perpendicular to the direction of the flow. Due to the buffering
      capacity of the IPG gel, proteins with an isoelectric point (pI) close to pH of
      the gel in contact with the flow chamber stay in solution because they are
      neutral and therefore not extracted by the electric field. Other proteins will be
      charged when approaching the IPG gel and are extracted into the gel by the
      electric field. Both a demonstration experiment with pI markers and a simulation
      of the electric field distribution are presented to highlight the principle of
      the system. In addition, an isoelectric fractionation of an Escherichia coli
      extract is shown to illustrate the possible applications.

PMID- 11840562
TI  - Stable isotope labelling in vivo as an aid to protein identification in peptide
      mass fingerprinting.
AB  - Peptide mass fingerprinting (PMF) is a powerful technique for identification of
      proteins derived from in-gel digests by virtue of their matrix-assisted laser
      desorption/ionization-time of flight mass spectra. However, there are
      circumstances where the under-representation of peptides in the mass spectrum and
      the complexity of the source proteome mean that PMF is inadequate as an
      identification tool. In this paper, we show that identification is substantially
      enhanced by inclusion of composition data for a single amino acid. Labelling in
      vivo with a stable isotope labelled amino acid (in this paper, decadeuterated
      leucine) identifies the number of such amino acids in each digest fragment, and
      show a considerable gain in the ability of PMF to identify the parent protein.
      The method is tolerant to the extent of labelling, and as such, may be applicable
      to a range of single cell systems.

PMID- 11840563
TI  - Comparative proteome analysis of Chlamydia trachomatis serovar A, D and L2.
AB  - Chlamydia trachomatis represents a group of human pathogenic obligate
      intracellular and gram-negative bacteria. The genome of C. trachomatis D
      comprises 894 open reading frames (ORFs). In this study the global expression of
      genes in C. trachomatis A, D and L2, which are responsible for different
      chlamydial diseases, was investigated using a proteomics approach. Based on
      silver stained two-dimensional polyacrylamide gel electrophoresis (2-D PAGE),
      gels with purified elementary bodies (EB) and auto-radiography of gels with 35S
      labeled C. trachomatis proteins up to 700 protein spots were detectable within
      the range of the immobilized pH gradient (IPG) system used. Using mass
      spectrometry and N-terminal sequencing followed by database searching we
      identified 250 C. trachomatis proteins from purified EB of which 144 were derived
      from different genes representing 16% of the ORFs predicted from the C.
      trachomatis D genome and the 7.5 kb C. trachomatis plasmid. Important findings
      include identification of proteins from the type III secretion apparatus, enzymes
      from the central metabolism and confirmation of expression of 25 hypothetical
      ORFs and five polymorphic membrane proteins. Comparison of serovars generated
      novel data on genetic variability as indicated by electrophoretic variation and
      potentially important examples of serovar specific differences in protein
      abundance. The availability of the complete genome made it feasible to map and to
      identify proteins of C. trachomatis on a large scale and the integration of our
      data in a 2-D PAGE database will create a basis for post genomic research,
      important for the understanding of chlamydial development and pathogenesis.

PMID- 11840564
TI  - The characterisation of novel secreted Ly-6 proteins from rat urine by the
      combined use of two-dimensional gel electrophoresis, microbore high performance
      liquid chromatography and expressed sequence tag data.
AB  - A proteomic study of rat urine was undertaken using two-dimensional gel
      electrophoresis, microbore high performance liquid chromatography, mass
      spectrometry and N-terminal sequencing. Five known urinary proteins were
      identified but two novel peptide fragments matched a large number of rat
      expressed sequence tags (ESTs) from a liver library. By combining protein
      chemical and nucleotide data, two 101-residue open reading frames with 90% amino
      acid identity were determined, rat urinary protein 1 (RUP-1) and RUP-2. The data
      established signal peptide removal and provided evidence for N-glycosylation. A
      third related sequence, rat spleen protein (RSP-1) was confirmed from EST
      searches. These three proteins have been submitted to SWISS-PROT as P81827,
      P81828 and Q9QXN2, respectively. A fourth novel homologue was found in porcine
      and bovine ESTs from embryo libraries. Alignment with known homologues showed
      conserved cysteine positions characteristic of a secreted subfamily of Ly-6
      proteins. In two cases, antineoplastic urinary protein and caltrin, these
      homologues have unverified functional annotations. The RUP sequences showed high
      scoring matches to three unrelated rat mRNAs subsequently established to be
      chimeric. Two of these share extended sectional identity to RUP-1 but the third
      may represent another novel Ly-6 homologue. These chimeras have caused serious
      annotation errors in secondary databases.

PMID- 11840565
TI  - Characterization of plasma factors that alter the permeability to albumin within
      isolated glomeruli.
AB  - Focal segmental glomerulosclerosis (FSGS) is responsible for intractable
      proteinuria and has become the leading cause of renal insufficiency in children.
      Protenuria in FSGS is probably due to the effect of one or more permeability
      plasma factors which increase the glomerular permeability to proteins. We
      fractioned serum from children with FSGS using two mixed chromatographic
      electrophoretic approaches and have purified ten proteins among several hundreds
      which maintained the original permeability activity after renaturation, utilizing
      an isolated rat glomeruli assay. Six proteins were successfully characterized by
      mass spectometry as fibulin, apolipoprotein J, vitronectin, albumin isoforms,
      gamma chain fibrinogen and mannan-binding lectin-associated serine protease. Both
      procedures utilized for purification were based on affinity chromatography with
      Protein A-Sepharose and ended with two-dimensional electrophoresis, whereas the
      intermediate steps were different. Cross inhibition with zinc and aprotinin of
      purified factors and whole FSGS serum indicate strong homology. These are the
      first data demonstrating permeability activity for serum proteins, an observation
      with important implications in pathogenesis of proteinuria. Determination of the
      serum levels of each protein and a careful differentiation of FSGS from normal
      serum could provide the basis for clarifying the mechanism of proteinuria.

PMID- 11840566
TI  - A functional proteomic analysis of secreted fibrinolytic enzymes from Bacillus
      subtilis 168 using a combined method of two-dimensional gel electrophoresis and
      zymography.
AB  - Here we describe a proteomic approach to detect fibrinolytic enzymes from the
      culture supernatant of Bacillus subtilis 168. Following isoelectric focusing
      without dithiothreitol, two gels, one for sodium dodecyl sulfate polyacrylamide
      gel electrophoresis (SDS-PAGE) and the other for zymography, were run in
      parallel. After silver staining of SDS-PAGE and activity staining of zymography
      gel, the two gels were superimposed to detect protein spots that coincided with
      clear zones on the zymography gel. We identified four protein spots and
      characterized them with matrix-assisted laser desorption/ionization mass
      spectrometry. Database search revealed that four spots contained at least one of
      the extracellular serine proteases such as WprA and Vpr. This combined method of
      two-dimensional gel and zymography can be used as a powerful tool to detect
      proteases from various organisms.

PMID- 11840567
TI  - Cluster analysis of an extensive human breast cancer cell line protein expression
      map database.
AB  - In the current study, the protein expression maps (PEMs) of 26 breast cancer cell
      lines and three cell lines derived from normal breast or benign disease tissue
      were visualised by high resolution two-dimensional gel electrophoresis. Analysis
      of this data was performed with ChiClust and ChiMap, two analytical
      bioinformatics tools that are described here. These tools are designed to
      facilitate recognition of specific patterns shared by two or more (a series)
      PEMs. Both tools use PEMs that were matched by an image analysis program and
      locally written programs to create a match table that is saved in an object
      relational database. The ChiClust tool uses clustering and subclustering methods
      to extract statistically significant protein expression patterns from a large
      series of PEMs. The ChiMap tool calculates a differential value (either as
      percentage change or a fold change) and represents these graphically. All such
      differentials or just those identified using ChiClust can be submitted to ChiMap.
      These methods are not dependent on any particular commercial image analysis
      program, and the whole software package gives an integrated procedure for the
      comparison and analysis of a series of PEMs. The ChiClust tool was used here to
      order the breast cell lines into groups according to biological characteristics
      including morphology in vitro and tumour forming ability in vivo. ChiMap was then
      used to highlight eight major protein feature-changes detected between breast
      cancer cell lines that either do or do not proliferate in nude mice. Mass
      spectrometry was used to identify the proteins. The possible role of these
      proteins in cancer is discussed.

PMID- 11840571
TI  - Guidelines for good medical practice in psychosomatic obstetrics and gynecology:
      entering the rat race?

PMID- 11840572
TI  - The prevalence of violence investigated in a pregnant population in Sweden.
AB  - All women registered for antenatal care within a Swedish municipality during a 6
      month period were assessed regarding acts of violence. The Abuse Assessment
      Screen was used on two occasions during pregnancy, and once between 4 and 20
      weeks after delivery. The efficacy of repeated interviews was investigated, and
      characteristics of abused and non-abused women were compared. The participation
      rate was 93% (1038 women). Physical abuse by a close acquaintance or relative
      during or shortly after pregnancy was reported by 1.3%, and by 2.8% when the year
      preceding pregnancy was included. The lifetime prevalence of emotional, physical
      or sexual abuse was 19.4%. Repeated questioning increased the detection of abuse.
      Women abused during pregnancy reported more preceding ill-health and more
      elective abortions than non-abused women. Intervention against sexual violence
      has been on the political agenda in Sweden for several decades. Even so, physical
      abuse is a risk factor comparable in frequency to obstetric complications such as
      gestational diabetes and pre-eclampsia. Routines need to be established to make
      questioning about violence an integral part of the standardized screening for
      risk factors during pregnancy.

PMID- 11840573
TI  - What doctors and patients think about false-negative sentinel lymph nodes in
      vulvar cancer.
AB  - The sentinel lymph node procedure is a relatively new, minimally-invasive method
      for the assessment of nodal status in malignancies such as breast cancer,
      cutaneous melanoma and vulvar cancer. Although highly accurate, this new method
      is inevitably associated with a certain false-negative rate, possibly leading to
      worse survival in a small subset of patients. The clinical implementation of the
      sentinel lymph node procedure is therefore a matter of ongoing debate, especially
      among doctors. The aim of this study was to assess opinions on the acceptable
      false-negative rate of the sentinel lymph node procedure in patients with vulvar
      cancer, who in the past had undergone standard routine radical vulvectomy and
      complete inguinofemoral lymphadenectomy (and frequently experienced
      complications), and in gynecologists treating patients with vulvar cancer.
      Structured questionnaires were sent to both patients and gynecologists. The
      patients had been treated for vulvar cancer between 1985 and 1993, and were all
      in complete remission with a median follow-up of 118 months (range: 76-185).
      Questions to the patients dealt with experienced side-effects of the standard
      treatment and opinion on the acceptable false-negative rate of the sentinel lymph
      node procedure. The response rate among patients was 91% (106/117). Forty per
      cent of the patients experienced one or more infections in the legs (cellulitis)
      and 49% of the patients still experience either severe pain and/or severe
      lymphedema in the legs. Sixty-six per cent of the patients preferred complete
      inguinofemoral lymphadenectomy in preference to a 5% false-negative rate of the
      sentinel lymph node procedure of 5%. Their preference was not related to age or
      the side-effects they had experienced. The response rate among gynecologists was
      80% (80/100), of whom 60% were willing to accept a 5-20% false-negative rate of
      the sentinel lymph node procedure. While gynecologists may consider the sentinel
      lymph node procedure to be a promising diagnostic tool, the majority of vulvar
      cancer patients, who have undergone complete inguinofemoral lymphadenectomy in
      the past and have frequently experienced complications, would not advise
      introduction of this technique because they do not want to take any risk of
      missing a lymph node metastasis.

PMID- 11840574
TI  - Birth as a multidimensional experience: comparison of the English- and German
      language versions of Salmon's Item List.
AB  - Results concerning satisfaction with the birth experience in different trials are
      difficult to compare, owing to a lack of internationally used research scales.
      Salmon's Item List (SIL) is easy-to-handle and would therefore be very helpful
      for research as well as for obstetric clinic quality control. Two hundred and
      fifty-one patients were investigated using a German-language version of SIL (SIL
      ger); the statistical evaluation was carried out by means of a principal
      components analysis. Principal components analysis revealed two major findings:
      (1) as stated by other authors the birth experience is multidimensional, each
      aspect influencing the others in a non-linear way; (2) in addition to Salmon's
      dimensions (i.e. postnatal 'fulfillment', intranatal 'physical discomfort' and
      intranatal 'emotional distress') another postnatal dimension labeled 'negative
      emotional experience' was detected. Not only are intranatal experiences
      multidimensional, but so too are evaluative feelings afterwards. In addition to
      fulfillment, as developed by Salmon, a dimension of negative emotional experience
      needs to be taken into account. This dimension does not correlate in a linear way
      with fulfillment. It is appropriate to use SIL in research. Before using it for
      purposes of clinical quality control, however, larger samples need to be
      evaluated in order to prove the stability of the factor structure.

PMID- 11840575
TI  - Honor your father and your mother.
AB  - While on the one hand there is much mutual love and care in the relationship
      between parents and their offspring, there may, on the other hand, be also much
      mutual 'sound and fury', which sometimes is far from 'signifying nothing'
      (William Shakespeare, Macbeth). Indeed, from conception on, individuals are
      confronted with parent-offspring conflicts of all kinds. Initially these
      conflicts concern physiological matters (implantation, nutrition, weaning, etc.),
      but later in life the accent is on psychological ('you must this', 'you must
      that', 'don't do that' etc.) and social affairs, and phenomena such as child
      abuse, infanticide and incest may occur. It is, therefore, certainly not self
      evident that children honor their parents. To reinforce their position, parents
      (societies) may appeal to a 'divine' commandment which helps them make their
      children suppress any tendency to conflict toward them (and hence to their
      culture), so that children conform to their parents' norms and values. When such
      psychological and sociological parent-offspring conflicts are not resolved
      satisfactorily, it can be suggested, children may (consciously or unconsciously)
      have aggressive feelings toward their parents: Freud's 'Oedipus complex'. This
      complex, it is argued, can also be seen as a parent-offspring conflict. Given
      their biological basis, parent-offspring conflicts can hardly be considered as
      abnormal. Conflicts between adults and their offspring have always existed and
      will always exist, simply because it is inherent in our genetic make-up: parents
      and offspring of sexually reproducing species--humans included--are only about
      50% genetically related and hence have different interests at all levels of
      being. Indeed, parent-offspring conflicts are such stuff as we are made on, and
      our little life is rounded with its consequences (adapted from William
      Shakespeare, The Tempest).

PMID- 11840576
TI  - Psychological and sexual functioning in women with vulvar vestibulitis.
AB  - OBJECTIVE: The purpose of the study was to compare psychological and sexual
      functioning in women with vestibulitis with healthy controls. It was hypothesized
      that women with vestibulitis would experience greater psychological stress and
      sexual dissatisfaction than controls. STUDY DESIGN: Fifty-two women with
      vestibulitis recruited from a vulvovaginal disease clinic and 46 healthy controls
      recruited from an outpatient gynecology clinic completed five standardized
      measures of psychological and sexual functioning. Multivariate analyses of
      variance and covariance were used to examine group differences. RESULTS: Women
      with vestibulitis reported significantly higher scores than controls on the
      measures of depression (p < or = 0.001), psychological distress (p < or = 0.001)
      and sexual depression (p < or = 0.001). They reported significantly lower scores
      on the measures of sexual satisfaction (p < or = 0.001), sexual behavior (p < or
      = 0.001) and sexual self-esteem (p < or = 0.01). CONCLUSION: The results of this
      study highlight the importance of addressing psychological distress and sexual
      dissatisfaction in women with vestibulitis.

PMID- 11840577
TI  - Security associated with pregnancy and childbirth--experiences of pregnant women.
AB  - The aim of this study was to describe security associated with pregnancy and
      childbirth. Security was described as a human need and as human value. Data were
      collected in semi-structured interviews in two maternity health care clinics.
      Data interpretation was based on the method of content analysis. A convenience
      sample of 20 volunteer Finnish women was interviewed during pregnancy. The
      elements creating security associated with pregnancy and childbirth were
      maternity health care, social support, sense of control, and attitudes. The
      feeling of security was manifested in different resources, feelings and behavior.
      If the feeling of security associated with pregnancy and childbirth was impaired,
      the participants would resort to their network of social support, contact health
      care or social welfare services, or try to achieve a sense of security by their
      own resources. Feeling secure during pregnancy influences the pregnant woman's
      resources, feelings and behavior. It is important that professionals in maternity
      health care talk with the client about issues that influence her individually
      experienced security associated with pregnancy and childbirth. These include
      examination of the client's network of social support and informing the client
      about the health care and social welfare services available.

PMID- 11840578
TI  - Obstetrician-gynecologists' attitudes towards premenstrual dysphoric disorder and
      major depressive disorder.
AB  - Nine hundred ninety-seven fellows of the American College of Obstetricians and
      Gynecologists were surveyed by mailed questionnaire regarding their attitudes
      toward the conceptualization, diagnosis and treatment of premenstrual dysphoric
      disorder (PMDD) and major depressive disorder (MDD). Hypothesized differences in
      attitudes based on age, gender and professional identity as a primary care
      provider versus non-primary care provider were examined. Comparisons between
      attitudes toward PMDD and MDD were also investigated. Approximately 36% of the
      questionnaires were completed and returned. Overall attitudes toward PMDD versus
      MDD were found to be significantly different. Roughly one in three respondents
      disagreed with statements indicating responsibility for and confidence in their
      ability to treat MDD, but not PMDD. When significant differences were found for
      age, gender and professional identity, younger physicians, women physicians and
      those who self-identified as primary care providers reported attitudes that may
      be more likely to be associated with diagnosis and treatment of MDD and PMDD in
      gynecologic practice. For example, about 41% of self-identified non-primary care
      providers and 14.8% of primary care providers disagreed with the statement
      'treating depression is my responsibility as a gynecologist'. Differences in
      gynecologists' attitudes toward MDD versus PMDD may be associated with under
      treatment of MDD in gynecologic practice.

PMID- 11840579
TI  - Foreseeing the future by reviewing the past--a reminiscence of Acta
      Anaesthesiologica Sinica through forty years and its prospect.

PMID- 11840580
TI  - Prevention of PONV with dexamethasone in female patients undergoing desflurane
      anesthesia for thyroidectomy.
AB  - BACKGROUND: Desflurane is associated with a higher incidence of 24-h
      postoperative nausea and vomiting (PONV) as compared with sevoflurane or
      isoflurane. Dexamethasone 5 mg i.v. is suggested to be the minimum effective dose
      for prophylaxis of PONV in women undergoing thyroidectomy with isoflurane
      anesthesia. The objective of this study was to investigate whether a 5 mg dose of
      dexamethasone could be enough for, or a larger dose at 8 mg, could be more
      capable of preventing PONV in women undergoing desflurane anesthesia for
      thyroidectomy. METHODS: One hundred and thirty five patients were assigned to
      receive one of three treatment regimens prior to induction i.e., dexamethasone 8
      mg i.v. (Group D8), dexamethesone 5 mg i.v. (Group D5) or saline (Group S).
      RESULTS: It was demonstrated that the prophylactic administration of either
      dexamethasone 8 mg or 5 mg significantly reduced the overall incidence of PONV in
      patients undergoing thyroidectomy with desflurane anesthesia (P < 0.001, Group D8
      vs. Group S; Group D5 vs. Group S). However, patients who received dexamethasone
      8 mg showed a higher incidence of complete responses (no vomiting or need of
      rescue antiemetic medication for a 24-h postoperative period) in comparison with
      those receiving dexamethasone 5 mg (86% vs. 67%; P < 0.01). CONCLUSIONS: The
      results of this study showed that in PONV prophylaxis, in female patients
      undergoing desflurane anesthesia for thyroidectomy, the effect of dexamethasone 8
      mg was superior to that of dexamethasone 5 mg.

PMID- 11840581
TI  - Reversal of mivacurium chloride: edrophonium of spontaneous recovery in
      microscopic laryngeal surgery.
AB  - BACKGROUND: A double-blind, randomized study was designed to compare the recovery
      manner of mivacurium infusion with or without edrophonium reversal in microscopic
      laryngeal surgery. Neuromuscular blockade was quantified using the train-of-four
      stimuli to the ulnar nerve and quantification of the ratio of the fourth twitch
      to the first twitch. METHODS: With the approval of the Human Studies Committee of
      the Taipei Veterans General Hospital and patient informed consent, 40 healthy
      (ASA I or II) patients with age from 24 to 54 years, undergoing microscopic
      laryngeal surgery were randomly selected for study. Mivacurium chloride 0.2 mg/kg
      was given intravenously, and then it was given in continuous infusion to maintain
      muscle relaxation at 90% twitch block during the procedure. At the end of
      operation, mivacurium infusion was terminated. In a double-blind manner, group I
      patients (n = 20) received intravenous edrophonium 1 mg/kg and atropine 0.01
      mg/kg for reversal when T1 was at 10% recovery whereas patients in Group II (n =
      20) received placebo in the same manner. Mean infusion rate, recovery index
      (RI50, time from T1 25% to T1 50%; RI75, time from T1 25% to T1 75%), extubation
      time, and discharge time between groups were compared. Nausea, vomiting, and
      dysrhythmias were also documented until the patient was discharged from hospital.
      RESULTS: The demographic data between two groups were similar. The recovery index
      (RI75) for group I was shorter than that of placebo group (5.3 +/- 2.19 min vs.
      7.3 +/- 0.9 min) and the difference was statistically significant (P = 0.017).
      There were no statistically significant differences in mean infusion rate,
      incidence of nausea and vomiting, and discharge time from the POR. The incidence
      of tachycardia or arrhythmia in group I was significantly greater than that in
      group placebo. CONCLUSIONS: Mivacurium, a short-acting nondepolarizing agent, is
      a suitable muscle relaxant for patients receiving microscopic laryngeal surgery.
      Recovery time with the use of edrophonium as reversal agent was shorter than with
      placebo, but extubation and discharge time did not differ in two groups. The time
      which could be saved by the use of edrophonium for reversal of mivacurium to
      hasten the maximal recovery appears to be less than a few minutes. Therefore,
      clinically, the value of routine use of edrophonium to obtain a faster recovery
      does not outweigh its demerits of cost and risk and is not worthy of
      recommendation.

PMID- 11840582
TI  - Incidence of oral tissue trauma after the administration of general anesthesia.
AB  - BACKGROUND: Administration of general anesthesia necessitates certain amounts of
      manipulation or instrumentation within the mouth that may cause some oral tissue
      injuries. The purpose of this study was to determine the incidence of oral tissue
      trauma after receiving general anesthesia. Some possible risk factors were
      explored. METHODS: Four hundred and four adult patients receiving surgical
      procedures under general anesthesia facilitated by endotracheal intubation were
      included in this prospective survey. In each patient detailed oral and dental
      conditions were evaluated and recorded by an oral surgeon before and after
      operation. The extent of oral tissue trauma were computed and the type and
      character of the injury were recorded. RESULTS: Twenty-eight patients (6.9%) were
      found to sustain various degrees of oral trauma that included soft tissue
      laceration, tooth fracture, prosthesis damage, tooth avulsion, ecchymosis and
      numbness of tongue. Preexistence of missing tooth, crown, and residual root were
      some possible risk factors that might predispose to complication. CONCLUSIONS:
      Oral tissue trauma as it seems to be a common anesthetic complication that should
      be considered as a recognized hazard of general anesthesia. Understanding and
      recognizing oral anatomical condition and pathological change before anesthesia
      may help the anesthesiologists in preventing oral and dental complications and
      thus to avoid legal suits.

PMID- 11840583
TI  - Premedication with low-dose oral midazolam reduces the incidence and severity of
      emergence agitation in pediatric patients following sevoflurane anesthesia.
AB  - BACKGROUND: Sevoflurane is a volatile anesthetic agent with low pungency, non
      irritating odor, and low blood/gas partition coefficient that makes it an
      attractive alternative to halothane. However, a high incidence of emergence
      agitation (EA) has been reported in pediatric patients after sevoflurane
      anesthesia. The underlying mechanism of sevoflurane-induced EA remains unclear.
      Rapid recovery of consciousness (emergence) from sevoflurane anesthesia has been
      proposed as one possible mechanism. We, therefore, hypothesized that sedatives
      such as midazolam may counteract sevoflurane's rapid emergence and thus reduce
      the incidence and the severity of sevoflurane-induced EA. METHODS: A prospective,
      controlled, single-blinded study was carried out in 88 ASA class I or II
      pediatric patients scheduled for elective outpatient surgery. Patients were
      assigned to receive either midazolam (oral midazolam, 0.2 mg/kg as anesthetic
      premedication) or saline (oral normal saline as premedication) before the conduct
      of anesthesia. When separation from parents was due its process was watched and
      evaluated. Induction of anesthesia and maintenance of anesthesia were uniform in
      both groups. Induction of anesthesia was made possible with 8% sevoflurane and
      N2O in 50% O2. Intubation was performed straight without the aid of muscle
      relaxant and the ventilator was set to maintain normocapnia. Anesthesia was
      maintained with 3% sevoflurane and N2O in 50% O2 until the surgery was over. All
      matters of relevant time periods were recorded (induction, surgical procedure,
      extubation and transportation). In the post-anesthesia care unit (PACU), adverse
      events, the incidence and the severity of EA, analgesic requirement, duration of
      PACU stay, and parental as well as PACU nurses' satisfaction were evaluated.
      RESULTS: A significant lower incidence and less severity of EA were noted in
      patients premedicated with midazolam. Less postoperaive analgesia was required in
      patients who had received midazolam. Although midazolam-premedicated patients
      remained sedated after sevoflurane anesthesia, the duration of the PACU stay was
      not significantly different from that of saline-treated patients. Both parents
      and PACU nurses were more satisfied with midazolam as premedication. No solid
      evidence showed that there was close correlation between the process of
      separation from parents and the occurrence of EA. CONCLUSIONS: Premedication with
      oral midazolam is safe, convenient and effective in decreasing the occurrence of
      sevoflurane-induced EA. It does not delay discharge from PACU and is suitable for
      outpatient surgery.

PMID- 11840584
TI  - A modified method for intubation of a patient with ankylosing spondylitis using
      intubating laryngeal mask airway (LMA-Fastrach)--a case report.
AB  - We present an instance of successful use of an intubating laryngeal mask airway
      (LMA-Fastrach) and a Cook airway exchanger (CAE) for ventilation and intubation
      in a patient with severe ankylosing spondilitis (AS) receiving total hip
      arthroplasty. This measure may serve as an effective alternative for airway
      management in patients with difficult airway. A 61-year-old male was scheduled
      for right total hip arthroplasty because of degenerative osteoarthritis. He had
      been suffering from extensive ankylosing spondylitis, with the cervical spine
      markedly fixed in anterior flexion. Besides he could not open his mouth widely
      (35 mm when fully open) also because of ankylosis of jaw. Although we advised an
      awake fiberoptic tracheal intubation for anesthesia but he refused owing to a
      previous painful experience. After induction of anesthesia with glycopyrrolate,
      fentanyl, thiamylal sodium and succinylcholine, we inserted a # 5 Fastrach ILMA
      for primary airway maintenance. Then through the lumen of the ILMA we introduced
      the CAE as a guide for endotracheal tube (ETT) intubation. After applying the
      RAPI-FIT adapter to the CAE, we connected it to the capnography monitor for the
      confirmation of airway. We finally inserted an endotracheal tube into the trachea
      using the CAE as a guide. The whole procedure was uneventful and smooth. In sum,
      the modified Fastrach intubation method may facilitate tracheal intubation in
      patients with severe ankylosing spondilitis. It may be an alternative way for
      successful airway management in patients with difficult airway.

PMID- 11840585
TI  - Diagnosis of progressive compression of the aortic true lumen with intraoperative
      transesophageal echocardiography during repair of dissection of thoracic aorta--a
      case report.
AB  - We report an incident of progressive compression of the true lumen of aorta which
      happened immediately after cardiopulmonary bypass (CPB) and was diagnosed with
      intraoperative transesophageal echocardiography (TEE) in a patient undergoing an
      emergent repair of type A aortic dissection under femoral perfusion. During the
      CPB period, intraoperative TEE revealed gradual expansion of the false lumen
      which nearly obstructed the true lumen of the dissected aorta. The possible
      mechanism was related with distension of the false lumen by a dominant flow from
      retrograde femoral perfusion of CPB. With the application of intraoperative TEE,
      we could easily detect the hemodynamic changes of thoracic aorta and find the
      real causes so as to solve the perfusion abnormalities.

PMID- 11840586
TI  - Anesthetic management of a patient with relapsing polychondritis--a case report.
AB  - Relapsing polychondritis is a rare multisystem disorder of uncertain etiology. It
      is characterized by recurrent and progressive destruction of both elastic and
      hyaline cartilages as well as connective tissue. Respiratory tract involvement is
      associated with high mortality and morbidity. General anesthesia may be required
      in these patients for tracheostomy, bronchoscopy, nasal reconstruction, aortic
      valve replacement, and recent tracheobronchial stenting which they usually
      sustain. Tracheostomy was once the most likely surgical procedure in relapsing
      polychondritis. However, this procedure is only effective in patients with upper
      subglottic involvement. In cases of extensive tracheobronchial involvement,
      tracheostomy is ineffective because the distant tracheal collapse below the
      tracheostomy is still unresolved. We would like to report a case of relapsing
      polychondritis with tracheobronchial involvement, who underwent an emergent
      tracheostomy. Tracheostomy with continuous positive airway pressure (CPAP)
      effectively improved her airway collapse. Herein, we also discuss the anesthetic
      management after review of the current literature.

PMID- 11840587
TI  - Bullous eruptions caused by extravasation of mannitol--a case report.
AB  - Extravasation is one of the common complications seen with intravenous infusion.
      We bring forward a case of subcutaneous mannitol extravasation, which caused
      swelling and multiple cutaneous bullous eruptions in the hand and forearm during
      craniotomy. Treatment consisting of elevation of the affected extremity and
      application of silver sulfadiazine ointment twice daily to the injured area was
      successful. The possible mechanisms relevant to extravasation and its tissue
      damage are reviewed and discussed. Selecting proper intravenous infusion site,
      using pliable catheters and frequent inspection are important steps for
      prevention of extravasation.

PMID- 11840588
TI  - Use of pro-, pre- and synbiotics in the ICU--future options.
AB  - Although the word synbiotics was coined to describe the combined action of pre-
      and probiotics, the ability to, like antibiotics, control infection, the term is
      now increasingly used in a wider sense, as a name for all the substances released
      by microbial fermentation in the lower gut. One obvious reason is that most of
      the substances released seem to influence the immune defense, increase resistance
      to disease, and, most important, prevent complications to surgery such as
      infections and thrombosis. Protection layer of lactobacillus does not exist only
      on the GI tract mucosa, it is important at all exterior body surfaces including
      those of the eye, the nose, the mouth, the respiratory tract, the vagina, not to
      forget the skin. It is clearly reduced at all sites when the patient is in the
      settings of ICU. Each human being has his/her own unique microbial collection,
      especially of strains of Bifidobacterium and Lactobacillus, and it should be
      possible to identify an individual on the basis of his/her personal intestinal
      microflora. The flora seems always to be significantly reduced in the sick,
      especially in connection with severe disease, care in ICU, and in patients with
      little food intake or on parenteral nutrition. Supply of both pre- and probiotics
      can modify functions such as appetite, sleep, mood and circadian rhythm, and this
      most likely through metabolites produced by microbial fermentation in the gut.
      Supply of lactic acid bacteria (LAB) can also significantly reduce serum levels
      of a variety of toxins such as endotoxin. An umbrella of supplemented probiotics
      could provide to the patients with liver cirrhosis a tool to reduce septic
      manifestations and the incidence of bleeding. LAB are effective in controlling
      diarrhea of both bacterial and viral origin. A series of experimental studies and
      several uncontrolled clinical studies support the idea of using probiotics in
      patients with IBD. Ecoimmunonutrition with pre- pro- and synbiotics offer to be
      suitable tools in the new millennium.

PMID- 11840589
TI  - [Current situation of domiciliary enteral nutrition in Galicia. A multicenter
      study].
AB  - AIM: To determinate the prevalence of patients with Home Enteral Nutrition (HEN)
      in Galicia. DESIGN: Transversal study. SUBJECTS: Patients aged > or = 14 years,
      treated with HEN in our community since January 1998 to December 1999. Population
      of reference was 1.789.983. METHOD: Questionnaire previously designed. MAIN
      RESULTS: During the study period were treated 2,784 patients which represent a
      prevalence of 10.34 cases/10,000 inhabitants, being 18.8 for La Coruna, 1.3 for
      Lugo, 0.4 for Ourense and of the 20.85 for Pontevedra. The mean age of the
      patients was of 56 +/- 2.29 years (range 14-96). The Clinics units that required
      more frequently HEN were the Medical Units (48.3%), followed of the Surgery Units
      (20.2%) and the Primary Care Units (19.2%). Neurological abnormalities (43.6%),
      Neoplasias (30.7%) and Intestinal Inflammatory Disease (10.5%) were patients more
      frequently required HEN. Regarding to administration route 58.3%, 28.46%, 9.87%,
      0.5% and 0.65% used oral, nasogastric tube, PEG, gastrostomy and yeyunostomy
      respectively. The Index of complications was 0.18 of patient-year, due to
      gastrointestinal anomalies 0.12 patient-year, mechanical 0.09 patient-year. The
      index of hospitalizations in relation to the nutritional treatment was 0.026
      patient-year. CONCLUSIONS: The prevalence of HEN in our community is of 10.34
      cases/10,000 inhabitants. This kind of treatment is more frequently in the areas
      with high-density population. The frequency of complications was low. This data
      may be useful to compare with date from other areas and countries.

PMID- 11840591
TI  - [Evaluation of the journal Nutricion Hospitalaria. II. Productivity and
      collaboration].
AB  - An analysis is effected of the production by authors publishing their papers in
      Nutricion Hospitalaria (Hospital Nutrition), as well as by the institutions at
      which these authors work. The productivity figures indicate a large group of
      sporadic authors, whereas the "regular contributors" exceed figure 1 in the
      indices established. In terms of collaboration, Nutricion Hospitalaria articles
      present between 3 and 5 signatories per paper, lower than in other journals in
      the same scientific field.

PMID- 11840590
TI  - [Gastric enteral intolerance in mechanically ventilated patients with traumatic
      cerebral lesion].
AB  - OBJECTIVE: To check the correlation between gastric intolerance and hypertension
      intracranial pressure and their association with the clinical parameters and
      severity indexes in patients with severe head injury (HI); to evaluate the
      advantages of transpyloric feeding. DESIGN: Prospective and observational
      clinical study. SETTING: Intensive Care Unit (ICM) of a General University
      Hospital. PATIENTS AND PARTICIPANTS: 25 brain injured patients requiring
      sedation, mechanical ventilation and hypertension intracranial monitoring.
      INTERVENTIONS: Analysis of the incidence of delayed gastric emptying (area under
      the curve (AUC60)) and of gastrointestinal intolerance; study of their
      correlation with hypertension intracranial, severity indexes and sedative
      medication administered; evaluation of the alternative effectiveness of
      transpyloric feeding. MEASUREMENTS AND RESULTS: 44% of the patients showed GI,
      which was measured by means of the paracetamol test (AUC60). The sedative
      medication was related to IG (p < 0.005), HIC (p < 0.01) and AUC60 (p < 0.01). Of
      the severity indexes, there was a correlation between Glasgow Coma Score and
      AUC60 (p < 0.01); the Marshall score HIC (p < 0.005) and AUC60 (p < 0.01). Of the
      quantitative variables, we found a correlation between HIC and IG (p < 0.001),
      HIC and pneumonia (p < 0.01), IG as well pneumonia (p < 0.001), and AUC60 (p <
      0.001) and AUC60 and pneumonia (p < 0.05). CONCLUSIONS: Enteral intolerance in
      patients with HI is due to delayed gastric emptying (DGE) which is proportional
      to the severity of the head injury and to the intensity of the systemic response.
      The high incidence of GI makes transpyloric feeding advisable in order to attain
      the nutritional objective and to reduce the risk of aspirative nosocomial
      pneumonia.

PMID- 11840592
TI  - [24-hour oral intake in patients with upper aerodigestive tumors].
AB  - BACKGROUND: A lot of works have shown, alterations in oral intake of micro and
      macronutrients, in patients with upper aerodigestive tumors. The main aim of our
      work was to compare the daily intake in a group of patients with upper
      aerodigestive tumors versus a control group. METHODS: A group pf 35 patients with
      upper aerodigestive tumors were studied (8 oral cavity and 27 larynx). A group of
      35 subjects were use as control group. In all patients the next parameters were
      taken; age, sex, smoking and alcohol consumption, type of tumors and a 24 hours
      oral intake questionnaire. RESULTS: Patients with upper aerodigestive tumors
      showed a high increase of calories intake (1545.3 +/- 359 cal/day vs 1264.4 +/-
      240 cal/day; p < 0.05), carbohydrates intake (177.9 +/- 57.9 g/day vs 135.9 +/-
      38.5 g/day; p < 0.05), total fats (58.2 +/- 18.4 g/day vs 45.9 +/- 15.4 g/day; p
      < 0.05) and saturated fats intake (19.4 +/- 7.7 g/day vs 11.9 +/- 6.1 g/day; p <
      0.05). In micronutrients intake differences were detected, a low intake in
      tumoral patients of vitamin C (59.4 +/- 18.5 mg/day vs 141.5 +/- 83 mg/dia; p <
      0.05), folic acid (116.5 +/- 56.3 mg/day vs 180.5 +/- 78.5 mg/day; p < 0.05), and
      vitamin B2 (1.53 +/- 0.5 mg/day vs 23.9 +/- 6.5 g/day; p < 0.05). In minerals
      intake we detected a low intake in tumoral patients of calcium (702.9 +/- 363
      mg/day vs 942.4 +/- 327 mg/day; p < 0.05). CONCLUSIONS: Patients with upper
      aerodigestive tumors take a high amount of calories, saturated fats and
      carbohydrates, and a low intake of vitamin C, folic, vitamin B12 and calcium.

PMID- 11840593
TI  - [Awareness of and attitude towards deviation in clinical medical practice].

PMID- 11840594
TI  - Correlates of psychiatric morbidity in patients with leprosy.
AB  - The relationship between psychiatric morbidity in 30 leprosy patients under
      treatment as assessed by the General Health Questionnaire (GHQ-12) and certain
      variables of their illness and psychosocial factors is examined in this paper.
      Physical disability and duration of illness were the illness variables
      considered; knowledge and adjustment were the psychosocial variables included.
      Bell's Adjustment Inventory (BAI) measured the latter, psychiatric morbidity was
      positively correlated with physical disability (p < 0.05), knowledge about the
      disease (p < 0.01) and social, emotional and health maladjustment (p < 0.01), but
      not with duration of illness (p > 0.05). The importance of appropriate knowledge,
      social stigma and physical disability in leprosy is discussed in addressing the
      psychiatric morbidity of leprosy patients.

PMID- 11840595
TI  - Comparative study of anti-PGL-1, anti-35 kDa and anti-lipoarabinomannan assays
      for serodiagnosis of leprosy.
AB  - Three antibody assays (anti-PGL-1, anti-35 kDa and anti-LAM) were used to
      determine the levels of antibodies in the sera of untreated leprosy patients. All
      the three assays showed higher levels of antibodies in BL/LL patients as compared
      to I and TT/BT patients, as well as healthy controls. BL/LL patients showed
      positivity of 100%, 84.2% and 78.9% by anti-PGL-1, anti-35 kDa and anti-LAM
      assays respectively. All the three assays were negative for leprosy in healthy
      controls. Anti-PGL-1 assay was positive in 20% of TT/BT patients and 17.9% of I
      patients. Anti-35 kDa assay was negative in all the TT/BT patients and positive
      in 7.14% of I patients. Anti-LAM assay was positive in 13.3% of TT/BT patients
      and in 10.7% of I patients. Hence, while these assays are valuable in diagnosing
      BL/LL patients, their usefulness in diagnosing I, BT or TT leprosy is limited.

PMID- 11840596
TI  - Poor correlation of systemic immunological parameters with clinical features in
      macular leprosy.
AB  - On the basis of clinical features and bacteriological status, macular skin
      lesions of nine cases of leprosy were classified as falling within a spectrum
      between the tuberculoid at one end and the lepromatous at the other. While
      histologic correlation was seen in 60% of cases, humoral and cellular systemic
      immunologic features were found to be uncharacteristic. It is suggested that
      macular lesions form an early stage in the development of leprosy where the
      systemic immunological response is yet to set in fully.

PMID- 11840597
TI  - History and development of the Hind Kusht Nivaran Sangh and its contribution to
      leprosy work in India.

PMID- 11840598
TI  - Actinomycotic mycetoma due to Nocardia brasiliensis in a case of leprosy.
AB  - Various bacterial and fungal infections associated with non-healing ulcers in
      cases of leprosy have been reported (G Ebenzer et al, 2000, Rama Ramani et al,
      1990). There are no reports of mycetoma associated with leprosy patients in the
      literature. We report here a case of actinomycotic mycetoma due to Nocardia
      brasiliensis associated with the non-healing plantar ulcer of a leprosy patient.

PMID- 11840600
TI  - Persisting M. leprae in a nerve in the pampiniform plexus of a lepromatous
      patient: an unusual finding.

PMID- 11840599
TI  - Lucio leprosy with lucio phenomenon.
AB  - Leprosy is one of the commonly seen disease in any dermatology outpatient
      department in our country. India accounts for a major portion of the leprosy
      patients in the world. All types of the disease, such as tuberculoid, borderline,
      lepromatous, neuritic and indeterminate leprosy, are seen. However, "lucio
      leprosy" which is considered a special type of lepromatous leprosy characterised
      by diffuse involvement has not been reported from India. We are presenting here
      two cases of "lucio leprosy" with "lucio phenomenon", the lucio phenomenon being
      a special type of lepra reaction seen in lucio leprosy.

PMID- 11840602
TI  - Admission procedure as predictor of performance in medical colleges.

PMID- 11840601
TI  - Changing face of leprosy in south India.

PMID- 11840603
TI  - Selection procedure as predictor of performance in university examination.
AB  - OBJECTIVE: To determine the correlation of SSC, HSC, ZMU achievement test and
      interview scores with the scores achieved in MBBS 1st, 2nd and 3rd Professional
      Examinations. METHOD AND PROCEDURE: The SSC, HSC, ZMU admission test and
      interview scores of 159 MBBS students admitted in 1995, 1996 and 1997 were
      correlated with the scores of the 1st, 2nd and 3rd professional examinations.
      Data analysis was done on SPSS Software. RESULTS: No significant relationship was
      found between the SSC, HSC, ZMU admission test and interview scores and the
      scores obtained in the professional examinations. SSC scores did not correlate
      with any variables/matrices, whereas for batches 1 and 2 the HSC school leaving
      examination scores correlated significantly with ZMU interview score (p < 0.05).
      No correlation was found between ZMU test and ZMU interviews. Results showed
      significant relationship (p < 0.01) between all 1st, 2nd and 3rd professionals of
      all three batches. CONCLUSION: None of the admission criteria (SSC, HSC, ZMU
      admission test and interview scores) predict the performance of medical students
      in the professional examinations.

PMID- 11840604
TI  - Development and testing of an assessment tool for integrated learning.
AB  - OBJECTIVE: Development of integrated questions for undergraduate medical students
      and assessing students' capability to retain and apply basic concepts in an
      integrated way. METHOD: Multiple choice questions, attempting to probe
      understanding and application of different concepts, affiliated with different
      subjects and topics, were developed. As a pilot these were administered to the
      students of third year and final year at the end of their certifying examinations
      as a mock test. The following year these questions were introduced in the
      continuous assessments and subsequently the certifying examinations (in third
      year) as 33% of the whole examination. Difficult indices, item analysis and
      internal consistency (alpha) were calculated for all the questions. RESULTS: The
      difficulty indices of integrated questions indicated that students found the
      integrated questions difficult. CONCLUSION: There was a significant change of
      distribution in terms of scoring for the integrated questions. Students' power to
      integrate showed reliable improvement when tested in the certifying examinations.

PMID- 11840605
TI  - Knowledge and misconceptions about sexually transmitted infections in married
      women--perspective from Islamabad.
AB  - OBJECTIVE: To study the knowledge of married women regarding existence of
      sexually transmitted infection (STI) their complications, treatment seeking, ways
      of preventing STI acquisition and opinion about sex education in schools/colleges
      and media. SETTING: The Mother and Child Health Center, a tertiary care hospital
      in Islamabad. METHODS: A cross-sectional survey based on sample of convenience
      was conducted, using a structured questionnaire with both close and open-ended
      questions. Trained women physician interviewers conducted the interviews after
      obtaining verbal consent. RESULTS: Out of 218 women approached for interviewing,
      only two refused to participate in the study. The mean age of the respondents was
      28.5 years (range 18-53 years). One hundred and sixty-eight (77.8%) respondents
      had heard/knew about sexually transmitted infections STIs. Two hundred and ten
      (97.2%) respondents had heard/knew about AIDS and out of these 162 (77.1%) knew
      that it is also transmitted through sexual contact. One hundred and eight two
      (84.2%) felt a need for sex education in the media, both print and electronic and
      204 (94.4%) respondents said that they would like to learn more about sexually
      transmitted infections. One hundred ninety four (98.8%) respondents had heard the
      Latin term Luekorrhoea. Of these 158 (81.5%) thought it was a gynecological
      disease. Majority thought it caused weakness. CONCLUSION: Widespread
      misperceptions were found to exist, which does not augur well for the effective
      prevention of STIs in the country. Population based studies are required to study
      the knowledge and epidemiology of STIs, as well as a need for a health education
      campaign in the country.

PMID- 11840606
TI  - Comparison of clinical and laparascopic features of infertile women suffering
      from genital tuberculosis (TB) or pelvic inflammatory disease (PID) or
      endometriosis.
AB  - OBJECTIVE: The objective of the study was to analyze the clinical and
      laparoscopic features, which may help to differentiate between infertility in
      females due to Genital Tuberculosis from Pelvic Inflammatory Disease (PID) and
      Endometriosis. METHODS: This case control study was carried out in a teaching
      tertiary care hospital. Medical records were searched from 1st January 1987 to
      31st December 2000 and 43 infertile women with biopsy proven genital tract
      tuberculosis were found. Equal number of infertile females with diagnosed PID and
      Endometriosis were randomly selected. Comparisons were done between features of
      Genital Tuberculosis with PID and Endometriosis separately and also genital
      tuberculosis with combined controls of PID and Endometriosis. RESULTS: Patients
      with genital tuberculosis commonly had primary infertility. PID and Endometriosis
      patients had early menarche and increased duration of menstruation. On physical
      examination, patients with Genital Tuberculosis were found to have short heights.
      No significant findings were observes in the pelvic examination and menstruation
      history between the comparison groups. Laparascopic examination revealed that
      fallopian tubes were abnormal, tortuous, bilaterally blocked and thickly adherent
      more commonly in Genital Tuberculosis when compared to other groups. CONCLUSION:
      The primary infertility patients with chronic malnutrition and massive adhesive
      fallopian tubes on laproscopic examination should be evaluated for genital
      tuberculosis.

PMID- 11840607
TI  - Phase 1 trial of ifosfamide and adriamycin in metastatic breast cancer.
AB  - OBJECTIVE: A Phase 1 trial was conducted in patients with estrogen negative
      receptors (ER) or hormone refractory metastatic breast cancer to determine the
      maximum tolerated dose (MTD) of ifosfamide with a fixed dose of doxorubicin. A
      secondary objective was to determine the efficacy of the combination in
      metastatic breast cancer. METHODS: Fifteen patients were entered in the study in
      cohorts of three patients at each dose level of ifosfamide. The dose of
      doxorubicin was fixed at 45 mg/m2. Five different dose levels of ifosfamide were
      tested ranging from dose level 1 of 1.5 gms/m2 day 1-3 to level V at 2.5 gms/m2
      day 1-3. RESULTS: Dose escalation of ifosfamide was stopped at 2.5 gms/m2. The
      MTD of ifosfamide was 2.25 gms/m2 day 1-3 in combination with doxorubicin. All
      patients in the study were assessable for toxicity. Neutropenia and
      thrombocytopenia were the major dose limiting toxicities. Other toxicities
      included anemia, confusion and hematuria. Objective responses were documented in
      11 of 15 patients (73.3%). Median time to treatment failure (TTF) was 13 months.
      Median overall survival (OS) was 18 months. CONCLUSION: The combination of
      ifosfamide and doxorubicin was a practical well tolerated regimen. There was
      substantial evidence of clinical activity in this phase I trial. This combination
      should be further evaluated, as an attractive alternative to taxanes for patients
      in developing countries where cost effectiveness is important.

PMID- 11840608
TI  - Prevalence of smokers among air-conditioned coaches, Pakistan.
AB  - OBJECTIVE: To estimate the proportion of smokers among passengers of air
      conditioned (A/C) coaches running between Karachi and Hyderabad. Pakistan.
      METHOD: A cross-sectional survey was done on passengers and staff members of 20
      air-conditioned coaches. RESULTS: Of 847 passengers interviewed, 17.3% were
      smokers and 11.7% passengers smoked during travel while rest of them remained
      passive smokers. Out of 147 smokers 91.2% were literate persons. Among staff
      members 59.3% were smokers. Approximately 56% of smokers among passengers were in
      the age range of 14-40 years. In 95% of A/C coaches there were no anti-smoking
      warning signs or written words present. CONCLUSION: In this study majority of
      smokers were literate, so inter-personal communication and counseling may change
      the smoking behavior. Ministry of Health should disseminate educational messages
      regarding hazards of passive smoking among commuters of AC coaches and above all
      proper implementation of legislation for smoking at public places especially in
      transport.

PMID- 11840609
TI  - Multi locular presentation of hepatocellular carcinoma.

PMID- 11840610
TI  - Tuberculosis of prostate.

PMID- 11840619
TI  - Our house. Assisted living providers fashion highly specialized facilities for
      residents with shared life experiences.

PMID- 11840620
TI  - Assisted living goes to Washington.

PMID- 11840621
TI  - Why some 'happy' customers walk away.

PMID- 11840622
TI  - Focus on caregiving. When it's time to call the doctor....

PMID- 11840623
TI  - More reasons to stay. Increasing services such as medication management and extra
      assistance with ADLs leads assisted living providers into uncharted territory.

PMID- 11840624
TI  - Top 30 assisted living chains.

PMID- 11840625
TI  - Patient abuse: when prevention strategies fail.

PMID- 11840626
TI  - From the shadow of OBRA.

PMID- 11840627
TI  - When to bill for ambulance services.

PMID- 11840628
TI  - Focus on caregiving. Assessing pain in nonverbal patients.

PMID- 11840629
TI  - Long-term care buyer's guide 2001.

PMID- 11840630
TI  - The hectic life of an MDS (minimum data set) coordinator.

PMID- 11840631
TI  - Pharmacy automation gains ground. Using technology to improve safety, efficiency.

PMID- 11840632
TI  - Adding fitness to the long-term care mix.

PMID- 11840633
TI  - The criminalizing of long-term care.

PMID- 11840634
TI  - Focus on caregiving. Learning to love the MDS.

PMID- 11840635
TI  - The ABCs of Internet security.

PMID- 11840636
TI  - AHCA corporate profiles 2001.

PMID- 11840637
TI  - Will claims workers dislike a computerized fraud detector?
AB  - The computerized fraud detector (CFRD) assigns suspicion scores to questionable
      automobile insurance claims. Evaluators pilot tested this algorithm in three
      offices, comparing its effects with three matched offices. Observers uncovered
      that in two target offices and one comparison office, Millennium 2000 (M2K) also
      was being installed. The study design thus became as follows: Two offices had two
      interventions, one office had CFRD but not M2K, another office had M2K but not
      CFRD, and two offices had neither. Hierarchical linear models document that
      offices with both new computer systems will have the most unfavorable employee
      attitudes toward computerized fraud detection, followed by offices with only one
      new system. Employees with jobs of higher rank and employees not receptive to
      innovation will dislike computerized fraud detection. Implementation of one
      computer system, CFRD or M2K, may have minor negative fixed effects on employee
      attitudes, but their effects on the between-office variance are inconsequential.

PMID- 11840639
TI  - Testing privatization of "long arm" service of process.
AB  - The research addresses questions about the desirability of privatizing a key
      component of the child support enforcement process, namely, the serving of legal
      documents or "service of process" for cases in which the noncustodial parent is
      living in another state. Child support enforcement cases that require this type
      of "long arm" service of process were randomly assigned to a private vendor and
      to out-of-state sheriff offices using an experimental research design. The author
      finds that although there is no difference in the time it took the two groups to
      process cases, the private vendor was more successful, on average, at performing
      this function. Furthermore, he finds that the higher success rate of the private
      vendor is sufficient to produce a substantively important increase in collections
      in child support enforcement cases. Additional questions about the suitability of
      privatizing "service of process" and other like services are also discussed.

PMID- 11840638
TI  - Evaluation of the effects of a smoking cessation intervention using the
      multilevel thresholds of change model.
AB  - The multilevel thresholds of change model is used to analyze the effect of a
      smoking cessation intervention on stage of readiness to quit across a 2-year
      follow-up period. The intervention, targeted to females with high school or less
      education, consisted of a televised component and a written manual. Any exposure
      to the intervention had a significant effect on stages that precede quitting but
      not on quitting; participation in the intervention had significant effects at all
      levels of change, including quitting. The written component had a stronger
      independent effect than the televised component. Intervention effects were
      strongest within women who were initially precontemplative.

PMID- 11840640
TI  - Evaluating the effects of information technology on problem-oriented-policing. If
      it doesn't fit, must we quit?
AB  - Technologies promise to make our organizations more productive, efficient or
      effective. But our experience does not always fulfill this promise. Public safety
      agencies are the target of a barrage of new information technologies offering
      better performance, many of which are attractive because they can be financed
      through federal grants. But when evaluations are performed of these technologies,
      improvements do not always result. This article describes the experiences of a
      state police agency (SPA) during its use of cellular digital packet data (CDPD)
      systems to support its problem-oriented policing (POP) project. The CDPD system
      should have improved the SPA's POP operations; in practice, it was not as clear.
      Although participants believed the CDPD technology worthwhile, there were only a
      few minor differences between POP officers that did and did not use it. This
      evaluation suggests the need for better databases to measure performance as well
      as more informed federal funding of ways to assess the impact of technologies.

PMID- 11840642
TI  - Dependence of malformation upon gestational age and exposed dose of gamma
      radiation.
AB  - In order to evaluate the importance of gestational age and the dose-incidence
      relationship by gamma radiation, pregnant ICR mice at gestational days from 2.5
      to 15.5 days post-coitus (p.c.) were exposed to a single dose of 2.0 Gy and also
      at day 11.5 after conception, which was the most sensitive stage for the
      induction of major congenital malformations. The animals were sacrificed on day
      18 of gestation and the fetuses were examined for mortality, growth retardation,
      changes in head size and other morphological abnormalities. The only demonstrable
      effect of irradiation during the pre-implantation period was an increase in
      prenatal mortality. Resorptions were maximal on exposure at day 2.5 after
      conception. The pre-implantation irradiated embryos which survived did not show
      any major fetal abnormalities. A small head, growth retardation, a cleft palate,
      dilatation of the cerebral ventricle, a renal pelvis, and abnormalities of the
      extremities and tail after exposure were prominent during the organogenesis
      period, especially on day 11.5 of gestation. As for the dose-incidence
      relationship, the incidence of a small head, growth-retarded fetuses, a cleft
      palate, dilatation of cerebral ventricle and abnormalities of the extremities in
      live fetuses rose as the radiation dose increased. The result indicated that the
      late period of organogenesis in the development of the brain, skull and
      extremities of a mouse was a particularly sensitive phase. The threshold doses of
      radiation that induced a cleft palate and dilatation of the cerebral ventricle,
      and abnormal extremities were between 1.0 and 2.0 Gy, and between 0.5 and 1.0 Gy,
      respectively.

PMID- 11840641
TI  - Sequence specificity of the 8-hydroxyguanine repair activity in rat organs.
AB  - The base excision repair system for 8-hydroxyguanine (8-OH-Gua) is believed to
      play a role in the prevention of mutations, such as GC-to-TA transversion, which
      leads to cancer development. However, the exact repair mechanism is still
      unclear. In this study, we examine whether the repair activity level for 8
      hydroxyguanine, one of the major forms of oxidative DNA damage, depends on the
      sequence of the substrate DNA. We prepared six different oligonucleotides
      containing 8-hydroxyguanine as substrates and reacted them with crude extracts
      from the livers and kidneys of 8-week-old Sprague-Dawley rats. As a result, up to
      a 10-fold difference in the repair activity levels was observed, depending on the
      substrates used. Based on this observation, we suggest that the repair systems
      may act with sequence specificity on the damaged DNA.

PMID- 11840643
TI  - The combined effects of MRI and X-rays on ICR mouse embryos during organogenesis.
AB  - The combined effects of X-rays and magnetic resonance imaging (MRI) on mouse
      embryos at an early stage of organogenesis were investigated. Pregnant ICR mice
      were irradiated on day 8 of gestation with X-rays at a dose of 1 Gy and/or MRI at
      0.5 T for 1 hour. The mortality rates of the embryos or fetuses, the incidence of
      external malformations, the fetal body weight and the sex ratio were observed at
      day 18 of gestation. A significant increase in embryonic mortality was observed
      after exposure to either 1 Gy of X-radiation or 0.5 T MRI. However, the combined
      X-rays and MRI did not show a statistically significant increase in embryonic
      mortality compared with the control. External malformations, such as exencephaly,
      a cleft palate and anophthalmia, were observed in mice irradiated with X-rays
      and/or MRI. The incidence of each malformation in all treated groups increased
      with statistical significance compared with the control mice. The incidence in
      mice irradiated with both X-rays and MRI was lower than in mice irradiated with
      only X-rays. The combined effects of the combination of radiation and MRI on the
      external malformations might be antagonistic. There were no statistically
      significant differences in fetal death, fetal body weight and sex ratio among all
      experimental groups.

PMID- 11840644
TI  - Effects of a 4.7 T static magnetic field on fetal development in ICR mice.
AB  - In order to determine the effects of a 4.7 T static magnetic field (SMF) on fetal
      development in mice, we evaluated fetal teratogenesis and endochondral
      ossification following exposure in utero. Pregnant ICR mice were exposed to a 4.7
      T SMF from day 7.5 to 9.5 of gestation in a whole-body dose, and sacrificed on
      day 18.5 of gestation. We examined the incidence of prenatal death, external
      malformations and fetal skeletal malformations. There were no significant
      differences observed in the incidence of prenatal death and/or malformations
      between SMF-exposed mice and control mice. Further, we evaluated the
      immunoreactivity for the vascular endothelial growth factor (VEGF), which is
      implicated in angiogenesis and osteogenesis, in the sternum of fetal mice
      following magnetic exposure. Our studies also indicated that on day 16.5 of
      gestation following SMF exposure, the immunoreactivity for VEGF was increased
      compared to unexposed controls. However, it was decreased in the exposed group
      compared to the control group on day 18.5 of gestation. DNA and proteoglycan (PG)
      synthesis were also measured in rabbit costal growth plate chondrocytes in vitro.
      No significant differences were observed in DNA synthesis between the SMF exposed
      chondrocytes and the control chondrocytes; however, PG synthesis in SMF exposed
      chondrocytes increased compared to the controls. Based on these results, we
      suggest that while SMF exposure promoted the endochondral ossification of
      chondrocytes, it did not induce any harmful effects on fetal development in ICR
      mice.

PMID- 11840645
TI  - Effects of 2-deoxy-D-glucose on DNA repair and mutagenesis in UV-irradiated
      yeast.
AB  - We have studied the effects of 2-deoxy-D-Glucose (2-DG) on the recovery of
      potentially lethal damage (PLDR), repair of chromosomal DNA, cyclobutane
      pyrimidine dimers (CPDs), reverse mutation and gene-conversion in UVC (254 nm)
      irradiated yeast. As studied by pulsed-field gel electrophoresis, post
      irradiation chromosomal DNA repair kinetics in a phosphate buffer (PB) with 10 mM
      glucose (G) was biphasic, where the first phase exhibited a decrease and the
      second phase showed an increase in the band intensities. A post-irradiation
      treatment in PB + G (10 mM) with 2-DG (10, 20, 50 mM) reduced the decrease in the
      DNA band intensities in the first phase of DNA repair. As compared to a post
      irradiation (125 J/m2) treatment in PB + G (10 mM), a treatment in PB + G (10 mM)
      + 2-DG (10 mM) showed a decreased PLDR, but increased revertants and gene
      convertants.

PMID- 11840646
TI  - Relationship between ultraviolet-B sensitivity and cyclobutane pyrimidine dimer
      photorepair in rice.
AB  - Among Indica rice cultivars (Oryza sativa L. cvs.) that belong to the aus ecotype
      from the tropical Bengal region, where the amount of ultraviolet-B (UV-B)
      radiation in the solar radiation is relatively great, Marich-bati cultivar has
      exhibited resistance to UV-B radiation, while Surjamkhi cultivar appeared to be
      less resistant. We have examined the susceptibility to cyclobutane pyrimidine
      dimer (CPD) induction by UV-B radiation and the ability to photorepair CPDs using
      these two cultivars. UV-B radiation produced similar dimer levels in the leaves
      of the two cultivars. In contrast, the ability to photorepair CPDs in the UV
      sensitive Surjamkhi cultivar was lower than that in the UV-resistant Marich-bati
      cultivar. These results were similar to our previous data, namely, that a UV
      sensitive Japanese rice cultivar (Oryza sativa L. cv. Norin 1) cultivated in the
      moderate climate of Japan is deficient in its ability to photorepair CPDs. Thus,
      these results suggest that a strong correlation exists between the sensitivity to
      UV-B and the photorepair deficiency, and that a low ability in CPD photorepair
      may be a principal factor in determining the UV-B sensitivity in rice plants.

PMID- 11840647
TI  - Medium-mediated bystander effects on HSG cells co-cultivated with cells
      irradiated by X-rays or a 290 MeV/u carbon beam.
AB  - The mechanisms of medium-mediated bystander effects on cell survival and
      micronucleus (MN) induction were investigated by co-cultivating unirradiated HSG
      cells with cells irradiated by X-rays or 290 MeV/u carbon beams. It was found
      that the survival of the irradiated cells exponentially decreased along with the
      dose, and that the plating efficiency (PE) of the unirradiated recipient cells
      was obviously more enhanced than that of the control cells. Moreover, MN was
      induced in the unirradiated recipient cells and its yield had a maximum
      distribution corresponding to the donor dose, which was different from the linear
      quadratic dose response of the yield of MN in the irradiated cells. The treatment
      of PTIO, a scavenger of nitric oxide (NO), decreased both PE and MN of the
      unirradiated recipient cells to control levels. Moreover, nitrite was detected in
      the co-culture medium, and its concentration was related to the donor dose. These
      results indicated that NO was involved in the above mentioned medium-mediated
      bystander effects. In addition, an equation was deduced to well fit the induction
      of MN of the unirradiated recipient cells.

PMID- 11840649
TI  - On immediacy: "vivid contrast between past and present".

PMID- 11840648
TI  - Reparability of lethal lesions produced by phosphorus photoabsorption in yeast
      cells.
AB  - The characteristics of DNA lesions produced by the photoabsorption of phosphorus
      in yeast cells were studied using monochromatized soft X-rays tuned to the
      absorption peak of the phosphorus K-edge (2153 eV) and below the peak energy
      (2147 eV). The repaired fractions of DNA double-strand breaks (dsb) were measured
      relatively by using both a mutant, rad 54-3, which shows the temperature
      sensitive dsb repair-deficient phenotype, and a wild-type strain. The repaired
      fraction of lesion in rad 54-3, which corresponds to the relative yield of dsb
      reparable by the RAD 54 pathway, was not affected by the phosphorus
      photoabsorption. Repair of the produced lesions in the wild-type cells was also
      measured by comparing the surviving fraction of the immediately plated cells to
      that of those cells plated after holding in a non-nutrient medium for 80 hrs. The
      recovery of the surviving fraction after the holding treatment was dependent upon
      the irradiated X-ray energy. These results suggest that irreparable lesions are
      produced by the inner-shell photoabsorption of phosphorus in DNA, although its
      yield is small.

PMID- 11840650
TI  - Defining the goals of a clinical psychoanalysis.

PMID- 11840651
TI  - Internalized homophobia in men: wanting in the first person singular, hating in
      the first person plural.
AB  - This paper focuses on the expression of internalized homophobia in men, arguing
      that the most powerful clinical use of this term depends upon its applicability
      to any man, without limitation to those whose primary object choice is
      homosexual. A number of dynamic situations are described to which the term might
      apply, elaborated by examples from contemporary culture and clinical practice. A
      central dynamic elucidated here is the move from an anxiety-ridden, first person
      singular voice to the promised safety of a first person plural voice--that is,
      from the dangerous position of "I want" to the more protected "we hate."

PMID- 11840652
TI  - Defenses against goodness.
AB  - This paper examines the fantasies and conflicts of analysands who avoid the
      experience and expression of positive reactions to the goodness of others and who
      hide feelings that would elicit that goodness. Envious wishes to spoil good
      objects, attachments to bad objects, defenses against gratitude and dependence,
      negative therapeutic reactions, and other such conflictual developments can help
      forestall depressive anxiety in these analysands. They dread abandoning
      narcissistic, omnipotent, sadomasochistic, and persecutory paranoidschizoid
      positions, and fear moving toward the mature depressive position, with its
      burdens of seemingly intolerable guilt, concern, felt ambivalence, and
      vulnerability to humiliation and disappointment.

PMID- 11840653
TI  - The innocence of sexuality.
AB  - The author explores aspects of sexual experiencing as they emerge in the course
      of development, especially as structured between parents and children. Is a
      certain mode of "innocent" sexual relating an important outcome of the
      developmental process, and does this mode have a place in the analytic process?
      The author suggests that the restoration of a capacity for sexual experiencing
      that is relatively free of convoluted developmental legacies may represent an
      important achievement in analytic work; and that the analyst's participation in
      this process, using his or her own capacity for "innocent" sexual responsiveness,
      may be essential to this outcome.

PMID- 11840654
TI  - Conviction and interpretation: hiding and seeking with words.
AB  - A patient who was developing her career as a writer evolved a unique process of
      reading her fiction aloud during analytic sessions. This paper explores this
      unconventional approach and the inevitable illusions, fantasies, meaningful
      explanations, and creative fictions that form a part of every
      technical/theoretical choice. How do analysts reach an integrated, rather than a
      theory-led, sense of conviction about a theoretical/technical choice? The
      development of integrated conviction is illustrated by showing the accumulation
      of ordinary, everyday emotional responses that are gradually integrated with
      theory, over time, until the analyst achieves an inner feeling of fit.

PMID- 11840655
TI  - [Fatty acid-induced reversal of general anesthesia: chain length-dependence of
      antagonizing potencies of fatty acids].
AB  - Anesthesia is always antagonized by high pressure in the range of 100 atm. The
      pressure reversal means that the volume of the macromolecule in the anesthetized
      state is larger than the awake state. Long-chain fatty acids tightened the
      structure of firefly luciferase whereas anesthetics unfolded the enzyme
      structure. As expected from these findings, myristate (C 14 fatty acid) at 40
      microM increased the EC50 values of volatile anesthetics 250% in goldfish. This
      study was performed to test the hypothesis that anesthesia antagonism by fatty
      acid in goldfish was caused by nonspecific action on proteins. We therefore
      studied the chain length-dependence of the antagonizing potencies of fatty acids.
      The chain length of 6, 8, 10, 12, and 14 was studied. Ten goldfish were placed in
      a tub containing 3200 ml distilled water without (control) or with fatty acids.
      After 30 min of bubbling with halothane vaporized with oxygen into the tub,
      goldfish were electrically stimulated by constant voltage 20 V for 0.2 sec. Those
      did not respond to the stimuli were counted as anesthetized. All fatty acids
      except C 10 increased EC50 of halothane by 50-100% compared to the control (1.13%
      atm). However, the fatty acid concentrations required for antagonizing halothane
      increased as the chain length decreased, 300 microM in C 6 30-fold higher than 10
      microM in C 14. Because water solubility of short-chain fatty acid is higher than
      long-chain fatty acid, the antagonizing potencies of fatty acids were thus
      determined not by their concentrations but by their thermodynamic activities
      (Ferguson's rule). These results suggest that fatty acid-induced anesthesia
      antagonism may be caused by physical and nonspecific actions on proteins.

PMID- 11840656
TI  - [Effect of ropivacaine on Ca function of skinned skeletal muscle].
AB  - It is well know that the amide-linked local anesthetics such as lidocaine
      accelerate Ca induced Ca release (CICR) rate. Since ropivacaine is a new amide
      linked local anesthetic, effects of ropivacaine on Ca functions were studied
      using skinned skeletal muscle. The extensor digitorum longus muscle of male
      Hartley guinea pigs of about 500 g was prepared for this study. According to
      Endo's method, CICR rates were measured using chemically skinned fibers.
      Ropivacaine accelerated the (CICR) rate only at concentrations of 3 mM and 10 mM
      with pCa 5.0. Ropivacaine at a concentration of 10 mM inhibited initial rate of
      Ca uptake by sarcoplasmic reticulum. Ca sensitivity of the contractile system was
      not affected with 10 mM of ropivacaine. These results suggest that ropivacaine
      can be used safely in patients susceptible to malignant hyperthermia since
      ropivacaine 3 mM is not a concentration for clinical use.

PMID- 11840657
TI  - [Effect of sevoflurane on spinal dorsal horn WDR neuronal activity in cats].
AB  - The effects of sevoflurane (0.5%, 1.5%, and 2.5%) on the spinal dorsal horn wide
      dynamic range (WDR) neuronal activity were studied in either spinal cord intact
      or spinal cord-transected cats. Extracellular activity was recorded in the dorsal
      horn from single WDR neurons responding to noxious and non-noxious stimuli
      applied to the cutaneous receptive fields on the left hind foot pads of intact
      cats or decerebrate and spinal cord-transected (L 1-2) cats. The experiment was
      divided into two sections. When bradykinin (BK) 10 micrograms was injected into
      the femoral artery contralateral to the recording site as a noxious test stimulus
      in the spinal cord-transected cat, 7 of 15 WDR neurons gave inhibitory responses
      which were depressed by 0.5%, 1.5%, and 2.5% sevoflurane. On the other hand, when
      the injection of BK 10 micrograms into the femoral artery contralateral to the
      recording site was used in the spinal cord-intact cat, all of 7 WDR neurons gave
      inhibitory responses, which were significantly depressed by 0.5%, 1.5%, and 2.5%
      sevoflurane. The results suggest that sevoflurane reduces the inhibition of
      dorsal horn WDR neuronal activities induced by BK injection in spinal cord-intact
      cats as well as in spinal cord-transected cats.

PMID- 11840658
TI  - [Two cases of intraoperative cerebral hemorrhage caused by undiagnosed metastatic
      brain tumors].
AB  - The authors report two cases of intraoperative cerebral hemorrhage caused by
      metastatic brain tumors. Delayed recovery from general anesthesia and
      neurological deficit were found in these patients. Brain CT in case 1 showed
      bilateral subdural hemorrhage and parenchymal massive hemorrhage in case 2. It is
      thought that the causes of hemorrhage are due to the changes in morphology of
      vessels, deterioration in cerebral circulatory regulated system, and increased
      intracranial pressure caused by tumors. Since the incidence of metastatic brain
      tumor has increased with prolonged survival time induced by progress in cancer
      therapy, preoperative brain examination and careful attention to vital signs
      during anesthesia are needed.

PMID- 11840659
TI  - [Intraoperative management for a patient with heparin-induced thrombocytopenia
      (HIT) undergoing off-pump coronary bypass surgery using argatroban, a direct
      thrombin inhibitor].
AB  - HIT type II is one of the severe complications of heparin therapy. The antibody
      for the heparin-PF 4 complex, which causes thrombocytopenia of less than 100 x
      10(3).microliter-1, thrombosis and DIC-like symptoms, is produced. We managed the
      patient with HIT type II, who underwent off-pump CABG using argatroban, a direct
      thrombin inhibitor, as an anticoagulant. Intraoperative activated coagulation
      time (ACT) was maintained above 250 sec with 5.0 micrograms.kg-1.min-1 of
      argatroban infusion and all the procedures were successful. We also investigated
      the platelet count in the 100 patients with heparin therapy in CCU. The incidence
      of the platelet depression after heparin administration was as high as 59%, and
      in 12% of the patients the platelet count dropped below 100 x 10(3).microliter-1.
      In conclusion, thrombocytopenia by heparin therapy is not rare, and argatroban as
      an anticoagulant during off-pump CABG is thought to be useful.

PMID- 11840660
TI  - [Accurate placement of central venous catheter--ECG-guided method vs patient
      height method].
AB  - Correct positioning of central venous catheters (CVC) is important. We compared
      the positioning of CVCs by ECG-monitoring via the guidewire and that by method
      using patient height. "Certofix" triple-lumen CVCs were inserted in 60 cardiac
      surgical patients via right internal jugular puncture. Of these, 30 were placed
      with ECG guidance via the guidewire (Group ECG), and 30 with reference to patient
      height (modified Pere's method) (Group H). The distance from CVC tip to the
      superior vena cava/right atrial junction (C-J distance) was measured by
      postoperative chest X-ray. There was no difference in height between the two
      groups. The depth of insertion of CVC and C-J distance (cm) were 15.1 +/- 0.3 and
      3.6 +/- 2.0 in group H and 14.3 +/- 1.5 and 4.9 +/- 1.2 in group ECG,
      respectively, with no statistically significant differences between the two
      groups. In one case of group H, the catheter tip was placed in the right atrium.
      In group ECG, there was a significant correlation between height and the depth of
      insertion of CVC. In conclusion, ECG guidance via the guidewire is useful for
      avoiding CVC displacement.

PMID- 11840661
TI  - [Anesthesia for a patient with Cockayne's syndrome].
AB  - Cockayne's syndrome is a rare, inherited, autosomal recessive disorder,
      characterised by dwarfism and progressive physical and mental retardation. A case
      is described of a 6-year-old girl (height 75 cm, weight 5.0 kg) with Cockayne's
      syndrome who was scheduled for liver biopsy under general anesthesia. Anesthesia
      was induced using 5% sevoflurane combined with 67% nitrous oxide in oxygen. After
      the end-tidal sevoflurane concentration of 3.5% had been maintained for 10
      minutes, laryngoscopy was attempted. The vocal cord was visualised and the
      trachea was intubated easily without muscle relaxant. Anesthesia was maintained
      with sevoflurane and nitrous oxide in oxygen. The procedure lasted for 13
      minutes. The tracheal tube was removed uneventfully following the return of
      adequate spontaneous respiration and airway reflexes. There were no postoperative
      problems. Concerning Cockayne's syndrome, there have been some reports of
      difficult airway, laryngospasm, aspirations of gastric contents and others. It is
      important to prevent laryngospasm by keeping the adequate depth of anesthesia for
      endotracheal intubation.

PMID- 11840662
TI  - [High dose L-dopa infusion during general anesthesia for gastrectomy in a patient
      with parkinsonism].
AB  - A 68-year-old man with parkinsonism was scheduled for gastrectomy. Levodopa 1400
      mg, droxidopa 300 mg and bromocriptine-mesylate 7.5 mg had been administered
      orally per day to control the symptom before surgery. On the day before surgery,
      oral medication was stopped and intravenous infusion of levodopa 100 mg.h-1 was
      started. Without any premedication but with levodopa infusion, anesthesia was
      induced with thiopental 175 mg and fentanyl 0.05 mg. Tracheal intubation was
      facilitated with vecuronium 6 mg and an epidural catheter was inserted.
      Anesthesia was maintained with O2, N2O and sevoflurane, combined with epidural
      block using mepivacaine. When blood pressure decreased, phenylephrine but not
      ephedrine was effective to increase blood pressure. Intravenous infusion of
      levodopa was continued for 19 days with decreasing doses from 8th postoperative
      day when injection of levodopa into the intestinal tube was started. On the 53rd
      day, he left the hospital without any complications. Serum concentrations of
      levodopa during and after surgery were 50 to 100 times higher than the
      therapeutic levels. However, he developed no complications, which suggests a wide
      safety range of levodopa. In conclusion, high dose levodopa infusion was
      effective in controlling the symptoms of Parkinsonism during general anesthesia.

PMID- 11840663
TI  - [A neonate with Beckwith-Wiedemann syndrome who developed upper airway
      obstruction after glossopexy].
AB  - We report a case of a female neonate with Beckwith-Wiedemann syndrome who
      manifested upper airway obstruction soon after birth and suffered from
      intractable hypoglycemia and abdominal distention caused by nephromegaly. She was
      delivered at 31 weeks of gestation with 2480 g and was diagnosed as Beckwith
      Wiedeman syndrome, manifesting macroglossia, hepatomegaly, nephromegaly and
      omphalocele. Her trachea was intubated 30 minutes after birth due to upper airway
      obstruction. At 12 days of life, glossopexy was performed to relieve the airway
      obstruction. Although tracheal extubation was successfully accomplished 12 days
      later, 21 days after the glossopexy she manifested apnea and hypoxia and required
      tracheal intubation and mechanical ventilation again. We suspected hypoglycemia
      or central apnea to be the cause of apnea and started the administration of
      somatostatin analog as a treatment for hypoglycemia. In addition to the apnea,
      abdominal distention caused by nephromegaly exacerbated her respiratory
      condition. At 69 days of life she died of sepsis complicated with disseminated
      intravascular coagulation and renal failure. A needle biopsy at autopsy revealed
      nephroblastomatosis.

PMID- 11840664
TI  - [Anesthetic experience of endoscopic umbilical cord ligation in a case of twin
      pregnancy with acardia].
AB  - We had an opportunity to engage in anesthetic management for umbilical cord
      ligation under endoscopy in a case of twin pregnancy with acardia. The patient
      was a 24-year-old woman. At the time of surgery, she was at 18 weeks and 2 days
      of pregnancy. Anesthesia was induced with diazepam 10 mg, fentanyl 150
      micrograms, and vecuronium 8 mg, and it was maintained with oxygen (1 l.min-1),
      air (3 l.min-1) and isoflurane 0.8 to 1.2%. To prevent uterine contraction,
      ritodrine administration was started before surgery and continued throughout the
      anesthesia. Throughout the surgery, the fetuses remained immobile, with no sign
      of uterine contractions. However, an arterial blood sample obtained after
      anesthetic induction showed mild lactic acidosis, suggesting its relation to
      ritodrine administration. Anesthetic management for fetal surgery is unique in
      that it is a non-obstetrical surgical procedure performed on a pregnant patient.
      Particular attention must be directed to specific aspects, such as the anesthetic
      effect on the fetus, uterine relaxation during peri-operative period, and
      prevention of spontaneous abortion or premature labor after surgery. The use of
      tocolytic agents and fetal monitoring remain for further investigation.

PMID- 11840665
TI  - [Droperidol causes multifocal ventricular dysrhythmias].
AB  - We report a case of ventricular chaotic arrhythmia after droperidol
      administration. A 49-year-old woman with chronic renal failure receiving
      hemodialysis, was scheduled for total hysterectomy under general anesthesia.
      General anesthesia was induced with thiopental 200 mg, fentanyl 0.1 mg and
      vecuronium 5 mg for endotracheal intubation. Anesthesia was maintained with 1%
      isoflurane and 60% nitrous oxide in oxygen. Droperidol 10 mg was injected for
      neuroleptanalgesia. After two minutes, ventricular chaotic arrhythmia occurred.
      Lidocaine 80 mg was injected. General anesthesia was stopped. After two minutes,
      arrhythmia disappeared. Several reports suggest that patients with preexisting
      conduction defects or prolonged QTc interval may be at risk to develop
      ventricular arrhythmias after droperidol administration. Administration of
      droperidol may have exaggerated prolongation of QTc interval.

PMID- 11840666
TI  - [Marked reduction of life-threatening ventricular tachyarrhythmias in a
      critically ill patient by intravenous administration of magnesium sulfate].
AB  - A 90-year-old man with ischemic heart disease underwent an emergent operation for
      a ruptured abdominal aortic aneurysm. The patient was brought to the operating
      room in a state of hypovolemic shock, and developed myocardial ischemia and
      intractable ventricular arrhythmias during the operation. Intensive
      cardiopulmonary resuscitation including rapid transfusion, external cardiac
      massage, electrical defibrillation, and extensive use of cardiovascular drugs
      restored hemodynamic stability temporarily. However, ventricular tachyarrhythmias
      readily recurred and caused cardiovascular collapse. Despite a normal value of
      blood ionized magnesium, we administered two grams of magnesium sulfate
      intravenously, which drastically reduced ventricular arrhythmias. Although a
      number of reports have shown the effectiveness of magnesium in correcting lethal
      ventricular arrhythmias, the rank of magnesium administration has not been well
      established in standard algorithms for arrhythmia therapy. Now that the
      concentration of ionized magnesium in the blood can be easily measured in
      clinical settings, its role as an antiarrhythmic agent should be extensively
      reevaluated.

PMID- 11840667
TI  - [Severe low back pain and muscular weakness in the thigh following urological
      surgery in the hyperlordotic position].
AB  - A 57-year-old male with prostatic cancer was scheduled for a radical
      prostatectomy under general anesthesia combined with epidural anesthesia. An
      epidural catheter was introduced at the L 1-2 interspace without problem. The
      patient was placed in a hyperlordotic supine position with a bolster under his
      lower back for the seven and a half hour operation. Upon emergence from
      anesthesia, he complained of severe low back pain in addition to incisional pain.
      On the second postoperative day, the epidural catheter was removed. After
      residural analgesic effects had fully disappeared, he experienced muscular
      weakness in the left thigh and could not walk. Regional sensory loss and edema
      were also observed where pressure had been applied by the bolster, although
      spinal cord magnetic resonance imaging studies were almost normal. It took him
      seven weeks to walk without the support of a brace after surgery. Hyperextension
      of the lumbar spine could increase the pressure on the inferior vena cava which
      is transmitted to the intraspinal vein, and could lead to the disci
      intervertebrales compression and the stress on the facet joint. We believe that
      the primary cause of the presented symptoms was related to this position.
      Prolonged and/or excessive hyperlordosis during surgery should be avoided.

PMID- 11840668
TI  - [Anesthetic management of a patient with hereditary spastic paraplegia].
AB  - We experienced the anesthetic management of a 39 year-old-male with hereditary
      spastic paraplegia (HSP) associated with pain due to pes cavus. He underwent
      orthomorphia ostectomy and tenodesis. Preoperative neurological examination
      revealed that he had slight dementia, symptoms of the pyramidal tract, lower limb
      bathyhypesthesia, and neurogenic bladder in addition to spastic paraplegia, and
      he was diagnosed as having combined type of HSP. Spinocerebellar degeneration is
      often accompanied with this type of HSP. To avoid the use of muscle relaxants and
      narcotics, we tried to induce anesthesia with inhalation of nitrous oxide (N2O),
      oxygen and sevoflurane (sevo). A laryngeal mask (LM) was inserted at the
      expiratory concentration of sevo 3.5%. Anesthesia was maintained by N2O, oxygen
      and sevo (2-3%) under spontaneous respiration. The patient recovered from
      anesthesia after the end of surgery, and the LM was removed smoothly. The
      patient's respiratory condition was stable, and no problems were found in the
      postoperative period.

PMID- 11840670
TI  - [A survey on cardio-pulmonary resuscitation knowledge of the nursing staff in the
      Asahikawa Medical College Hospital].
AB  - We surveyed the knowledge of the 66 nursing staffs on cardio-pulmonary
      resuscitation (CPR) and compared the results with that of 53 students of the
      Department of Nursing of the Asahikawa Medical College. The average scores of the
      test among the nursing staffs and the student nurses were 61 points and 54
      points, respectively. Although a significant difference in the percentage of
      total correct answers was demonstrated between the two groups, the rate of
      correct answers of the observation items was high, whereas that of skill items
      was comparatively low in each group. The "Ability" defined as an indicator of
      capability of practicing CPR of the nursing staffs was 17% and that of the
      student nurses was 0%. Our results show that the CPR knowledge of both the
      nursing staffs and the student nurses was not sufficient, indicating the
      necessity of CPR education for both nursing staffs and student nurses.

PMID- 11840671
TI  - [Concentrations of sevoflurane with and without nitrous oxide to block vasomotor
      reflexes to incision (MACBVR)].
AB  - The minimum alveolar concentration of an anesthetic that blocks the skin
      vasomotor reflex to surgical incision (MACBVR) for sevoflurane was determined in
      37 patients aged 30-60 years scheduled for laparotomies with or without nitrous
      oxide. Thirty seven patients were randomly allocated to one of the two groups: a
      sevoflurane group and a sevoflurane/N2O (50 vol%) group. The skin blood flow of
      the finger tip was measured using a laser Doppler flowmeter. Anesthesia was
      induced with sevoflurane and N2O and tracheal intubation was facilitated with
      vecuronium 0.1 mg.kg-1. Predetermined end tidal concentrations of sevoflurane and
      N2O were maintained for at least 15 min before incision. The MACBVR values of
      sevoflurane in O2 and in the presence of 50% N2O were 3.07% and 1.63%,
      respectively. The MACBVR level in the total anesthetic MAC multiple was 1.75 MAC
      for sevoflurane alone and the value decreased to 1.43 MAC when 50% N2O was used.
      There were no relations between the amplitude of the reduction in skin blood flow
      and the changes of hemodynamic variables in each group. However, the changes in
      SBP and HR at incision were significantly suppressed by addition of N2O (changes
      in SBP and HR: 41.6 +/- 20.4 mmHg and 35.4 +/- 12.5 bpm in the sevoflurane group
      vs. 24.6 +/- 10.2 mmHg and 18.1 +/- 9.5 bpm in the sevoflurane/N2O group, P <
      0.01). The results suggest that N2O is useful to suppress adrenergic responses to
      a surgical stimulus during sevoflurane anesthesia.

PMID- 11840672
TI  - [Perioperative mortality and morbidity in the year 2000 in 502 Japanese certified
      anesthesia-training hospitals: with a special reference to ASA-physical status-
      report of the Japan Society of Anesthesiologists Committee on Operating Room
      Safety].
AB  - Perioperative mortality and morbidity in Japan from Jan. 1 to Dec. 31, 2000 were
      studied retrospectively. Committee on Operating Room Safety in Japanese Society
      of Anesthesiologists (JSA) sent confidential questionnaires to 794 certified
      training hospitals of JSA and received answers from 67.6% of the hospitals. We
      analyzed their answers with a special reference to ASA physical status (ASA-PS).
      The total number of anesthesia available for this analysis was 897,733. The
      percentages of patients with ASA-PS of I, II, III, IV, I E, II E, III E, and IV E
      are 38.0, 40.3, 8.5, 0.4, 4.3, 5.3, 2.5, and 0.7%, respectively. Mortality and
      morbidity from all kinds of causes including anesthetic management,
      intraoperative events, co-existing diseases, and surgical problems were as
      follows. The incidences of cardiac arrest (per 10,000 cases of anesthesia) were
      1.11, 3.26, 12.25, 54.60, 0.77, 4.46, 21.08 and 217.75 in patients with ASA-PS of
      I, II, III, IV, I E, II E, III E, and IV E, respectively. The incidences of
      critical events including cardiac arrest, severe hypotension, and severe
      hypoxemia were 6.89, 20.22, 62.18, 148.21, 6.71, 20.38, 106.72 and 592.21 in
      patients with ASA-PS of I, II, III, IV, I E, II E, III E, and IV E, respectively.
      The mortality rates (death during anesthesia and within 7 postoperative days)
      after cardiac arrest were 0.26, 0.77, 3.69, 41.60, 0.00, 1.06, 9.42 and 163.31
      per 10,000 cases of anesthesia in patients with ASA-PS of I, II, III, IV, I E, II
      E, III E, and IV E, respectively. The overall mortality rates were 0.32, 1.38,
      9.75, 70.20, 0.26, 2.12, 29.15 and 353.02 in patients with ASA-PS of I, II, III,
      IV, I E, II E, III E, and IV E, respectively. Overall mortality and morbidity
      were higher in emergency anesthesia than in elective anesthesia. ASA-PS
      correlated well with overall mortality and morbidity, regardless of etiology. The
      incidences of cardiac arrest totally attributable to anesthesia were 0.23, 0.50,
      1.32, 0.00, 0.00, 0.85, 2.69 and 4.95 in patients with ASA-PS of I, II, III, IV,
      I E, II E, III E, and IV E, respectively. The incidences of all critical events
      totally attributable to anesthesia were 3.13, 5.56, 11.46, 5.20, 3.87, 5.94,
      13.90 and 14.85 in patients with ASA-PS of I, II, III, IV, I E, II E, III E, and
      IV E, respectively. The mortality rates after cardiac arrest totally attributable
      to anesthesia were 0.03, 0.03, 0.00, 0.00, 0.00, 0.21, 0.45 and 3.30 in patients
      with ASA-PS of I, II, III, IV, I E, II E, III E, and IV E, respectively. The
      overall mortality rates totally attributable to anesthesia were 0.03, 0.06, 0.00,
      0.00, 0.00, 0.21, 0.45 and 6.60 in patients with ASA-PS of I, II, III, IV, I E,
      II E, III E, and IV E, respectively. The overall mortality rate totally
      attributable to anesthesia among patients with good physical status (ASA-PS of I,
      II, I E, II E) was 0.05. Anesthetic management was mainly responsible for
      critical events in patients with good physical status, while coexisting diseases
      were in those with poor physical status. Surgical problems including procedures
      and massive hemorrhage were the leading causes of mortality in patients with good
      physical status. We reconfirmed that ASA-PS is useful to predict perioperative
      mortality and morbidity. It also seems likely that we should make much more
      efforts to reduce anesthetic morbidity in patients with good physical status, and
      to improve preanesthetic assessment and preparation in those with poor physical
      status. Reducing mortality and morbidity from surgical problems is also required
      for improving perioperative mortality.

PMID- 11840673
TI  - [mRNA surveillance].

PMID- 11840674
TI  - [His-Asp phosphorelay signal transduction].

PMID- 11840675
TI  - [Development of a new technology to manipulate gene activity by photo
      illumination using a new DNA/RNA caging compound, Bhc-diazo].

PMID- 11840676
TI  - [Retrotransposition of group II intron].

PMID- 11840677
TI  - [Unusual structure and its biological implications of GGA triplet repeat DNA].

PMID- 11840678
TI  - [NMR structural study of disulfide intermediates of hen lysozyme: toward
      unraveling the protein folding problem].

PMID- 11840679
TI  - [First atomic view of alpha V beta 3 integrin extracellular domain].

PMID- 11840680
TI  - [Modern methods for protein fold recognition].

PMID- 11840681
TI  - Smallpox eradication: destruction of variola virus stocks.

PMID- 11840682
TI  - Legacy of implementing industrial health and safety in developing countries.
AB  - Aiming to develop public attention to the hindrance of national and international
      efforts on industrial health and safety, this paper explores some important
      issues, such as the reasons for the lack of motivation to implement necessary
      measures in developing countries. Examples are likewise given to show why working
      people are significantly exposed to a number of occupational problems that are
      reflected in a deterioration of their health, safety and well being. In lieu
      thereof, an introduction of health and safety is not itself a solution, if
      certain changes are not rationalised according to the local need. While health
      and safety intervention is concerned, then local need is of prime importance. If
      individual situation is not clearly outlined, then preventive and control
      measures can be treated as a de facto measure. Hence immediate attention,
      collaboration and co-operation is needed from all the concerned parties such as
      local government authorities, semi-government or private organisations and
      international communities for proper implementation of work regulations as well
      as industrial acts and rules in various workplaces in each of the developing
      countries.

PMID- 11840683
TI  - Utility of ADL index for partially dependent older people: discriminating the
      functional level of an older population.
AB  - In the present study, the ADL index for the partially dependent older people
      (Demura et al., 1999) was applied to 218 bedridden (BED), 466 partially dependent
      (PD) and 245 independent living (IL) people in older groups. The purposes of this
      study were to clarify the meaning of the evaluation of this index and to examine
      how ADL items are useful in determining each older group. It is suggested that a
      perfect score with our ADL index means independent living level, and a score of
      zero means bedridden level. The results of discriminant analysis indicated that
      four items with low-difficulty, such as "eating," "going to the toilet," "tossing
      about in bed" and "writing," are useful in determining if the PD is becoming
      bedridden. While five items with high-difficulty, such as "putting on slacks,"
      "putting on trousers," "standing up from a sitting posture," "going up stairs"
      and "washing the whole body," are useful in determining if the PD is becoming
      independent living. Furthermore, it is inferred that the possibility of falling
      into a bedridden situation increases when the total score is 5 or less, while the
      functional level is close to independent living when the total score is 13 or
      more. These findings make clear the meaning of the evaluation of our ADL index.
      Furthermore, the functional level of older population may be screened using
      evaluation of total and item scores of this ADL index.

PMID- 11840684
TI  - Effect of skin pressure by clothing on small bowel transit time.
AB  - We examined the effect of increased skin pressure from tight clothing on small
      bowel transit time by means of the breath hydrogen test, using milk that
      contained lactulose as an additional indigestible disaccharide, which is used as
      a test meal after overnight fasting. In this experiment, we measured the small
      bowel transit time from 9 healthy and non-constipated female subjects with two
      different skin pressures that were applied by loose-fitting experimental garment
      or an additional tight-fitting girdle on two consecutive days. The skin pressure
      of the latter condition was 8-9 mmHg higher than that of the former one on the
      participants' waist, abdomen and hip region. The experimental order of the two
      skin pressure conditions was counterbalanced. As a result, the small bowel
      transit time obtained with and without girdle did not differ significantly (165.0
      +/- 26.0 minutes for less skin pressure condition and 173.3 +/- 26.8 minutes for
      more skin pressure condition, n = 9, p = 0.43). This result indicated that the
      skin pressure from clothing has no effect on the passage rate of food through the
      small intestine.

PMID- 11840685
TI  - Acute phase proteins, body temperature and urinary melatonin under the influence
      of bright and dim light intensities during the daytime.
AB  - Concentrations of five acute phase proteins: C-reactive protein (CRP), alpha 1
      antichymotrypsin (ACT), transferin (Tf), alpha 2-macroglobulin (alpha 2-M) and
      haptoglobin (Hp) as well as glycosylation profiles of alpha 1-antichymotrypsin
      (ACT) were studied in sera samples with 7 healthy volunteers under the influence
      of two different light intensities during the daytime dim (100 lx) and bright
      (3000 lx) light. Concentration of transferin (negative proteins) under the
      influence of bright light during the daytime decreased significantly. Other
      proteins have the tendency to increase (positive proteins) under the influence of
      daytime bright light. The microheterogeneity of ACT did not change under the
      influence of different light intensities. Melatonin and rectal temperature were
      also measured simultaneously. Rectal temperature decreased to be lower during the
      first half of the night and urinary melatonin secretion rate increased to be
      higher during the night when the subjects spent time under the bright light
      during the day. Thus, it is concluded that the diurnal bright light exposure may
      activate some parameters of acute phase proteins, increase nocturnal melatonin
      secretion and accelerate a fall of rectal temperature during first half period of
      night sleep.

PMID- 11840686
TI  - The relationships among exercise behavior, functional ADL, and psychological
      health in the elderly.
AB  - The purpose of this study was to examine the relationships among exercise
      behavior, the ability to live independently as assessed by functional activities
      of daily living (ADL), and psychological health as measured by the Philadelphia
      Geriatric Center morale scale, using data from 202 elderly residents aged 70 and
      living in their own home. The main results obtained from the analysis were as
      follows. 1. Exercise behavior had a significant effect on functional ADL. In
      particular, subjects who had been exercising regularly for 6 months or longer had
      higher functional ADL than subjects who did not exercise. 2. For psychological
      health, the functional ADL level was statistically significant, whereas exercise
      behavior was not. 3. Multiple regression analysis showed a positive and
      significant association between psychological health and functional ADL, but not
      between psychological health and exercise behavior, gender or family type. The
      results of this study demonstrated that elderly people's efforts to maintain and
      enhance their psychological health play important roles in their ability to live
      independently, and that regular exercise is necessary to an elderly person's
      ability to live independently.

PMID- 11840687
TI  - Influence of bright light during daytime on sleep parameters in hospitalized
      elderly patients.
AB  - Nurses frequently care for sleepless elderly patients on bed rest in a hospital
      environment. Our previous study with young adults showed that bright light
      exposure during the daytime affected the induction of nocturnal deep sleep. The
      purpose of this study is aimed at finding whether similar research could be
      observed with hospitalized elderly patients. Seven patients (mean age 67; range
      57-77 yrs, males 3: females 4) served as participants and their informed written
      consent was obtained. A fluorescent lamp fixed in the bed frame near the head of
      the patient was turned on at 10:00 h and off at 15:00 h each day for 1 week (BL).
      Moreover, each patient was required to stay near this light during this period.
      The patients lived in a room facing north, where the ambient light intensities
      ranged from 50 to 300 lx during the daytime. Their activities were continuously
      measured using an Actiwatch (model-AWL, Mini-Mitter, USA). Salivary samples were
      collected at midnight for the measurement of melatonin. The findings were
      compared between 2 days before BL exposure (baseline) and the last 2 days during
      BL exposure, respectively. The bright light exposure during the daytime prolonged
      "Time in Bed" (p < 0.05), increased "Immobile Minutes" (p < 0.05), and delayed
      "Get up Time" (p < 0.01). The average melatonin secretion at midnight in four
      patients increased from 7.5 +/- 2.6 pg/ml to 13.3 +/- 9.2 pg/ml. These findings
      suggest that diurnal bright light exposure for hospitalized elderly patients
      lying in bed under dark condition during the daytime may favor clinically the
      induction of nocturnal deep sleep. Attention should be given to the illumination
      conditions for elderly patients in hospitals to improve their impaired sleep.

PMID- 11840688
TI  - Vegetarian diet ameliorates symptoms of atopic dermatitis through reduction of
      the number of peripheral eosinophils and of PGE2 synthesis by monocytes.
AB  - Many patients with atopic dermatitis are dissatisfied with conventional
      treatments based on topical steroids and have experienced some traditional
      remedies and alternative therapies. However, most of such therapies have not been
      evaluated scientifically and clinically by specialists. This study was designed
      to assess whether a certain vegetarian diet might be effective for atopic
      dermatitis and if so, to identify the mechanisms of this remedy through analyses
      of immunological parameters. An open-trial study was carried out in twenty
      patients with atopic dermatitis. An improvement of dermatitis was evaluated by
      SCORAD index and serological and immunological parameters were monitored. After a
      two-month treatment, the severity of dermatitis was strikingly inhibited, as
      assessed by SCORAD index and serological parameters including LDH5 activity and a
      number of peripheral eosinophils. A sharp reduction in eosinophils and
      neutrophils was observed prior to improvement in the skin inflammation. In
      addition, PGE2 production by peripheral blood mononuclear cells was reduced by
      this treatment. In contrast, serum IgE levels did not change during the same
      period. Although this study is an open-trial one, it suggests that this treatment
      may be useful for the treatment of adult patients with severe atopic dermatitis.

PMID- 11840689
TI  - Epidemiological study on improving the QOL and oral conditions of the aged--Part
      1: The relationship between the status of tooth preservation and QOL.
AB  - In part 1 of this epidemiological study, a survey was conducted for all senior
      citizens aged 70 and over who resided in a mountainous village in the mid-section
      of Hyogo Prefecture. It focused on the relationship among the number of existing
      teeth, life environment, health status, and activities of daily living; and the
      correlation between oral status and QOL was analyzed. The daily activities of
      individuals were compared between those having one or more teeth and others who
      were totally edentulous. Subsequently, it was found that for both males and
      females, the odds ratio was significantly high for the dentulous individuals, in
      comparison with edentulous individuals, to exhibit a behavior indicative of a
      better QOL (such as "opportunity for conversation with family members or
      others)", "regular physical activities", and "attend meetings or group outings").
      The result of this survey indicates that the presence of teeth is very closely
      related to one's daily activities. It was concluded that preventing tooth loss is
      vital for maintaining the masticatory function; so to prevent tooth loss,
      periodontal disease must be averted.

PMID- 11840690
TI  - Epidemiological study on improving the QOL and oral conditions of the aged--Part
      2: Relationship between tooth loss and lifestyle factors for adults men.
AB  - Oral health in early- and mid-adulthood is essential for the improvement of one's
      QOL, this study was investigated to include an epidemiological analysis of the
      relationship between tooth loss and life style, such as smoking, regular
      exercise, and the food habits of approximately 2,000 employees. Compared with the
      group with mild or no periodontal disease (CPI of 0, 1, or 2), the frequency of
      tooth loss in the group with advanced periodontal disease (CPI of 4) was 2.00
      times (odds ratio, 2.00; 95% confidence limit, 1.37 to 2.93). The probability of
      tooth loss showed statistical significance in relation to smoking, alcohol
      drinking, and frequency of meals. Compared with non-smokers, the probability that
      current smokers will lose teeth is 1.53 times greater (odds ratio, 1.53; 95%
      confidence limit, 1.20 to 1.96). It was concluded that periodontal disease and
      smoking must be averted for preventing tooth loss.

PMID- 11840691
TI  - Distributions of skin thermoreceptors and clothing weights of Korean urbanites
      and farmers.

PMID- 11840692
TI  - Rheumatoid arthritis. The genetic components.
AB  - Rheumatoid arthritis is a multifactorial disease, with genetic, environmental,
      and stochastic components to its susceptibility. The search for susceptibility
      genes is still in progress. Preliminary results suggest the involvement of
      multiple genes, each with relatively modest effect. Genes within the major
      histocompatibility complex appear to have the strongest influence on disease
      susceptibility.

PMID- 11840693
TI  - Recent advances in the genetics of systemic lupus erythematosus.
AB  - In recent years, we have witnessed an explosion in our understanding of the
      biology of SLE through the study of lupus-prone mice and the identification and
      subsequent narrowing of the genomic intervals likely responsible for SLE in human
      beings. The data from these efforts support the hypothesis that multiple genes
      contribute to disease susceptibility. Clearly, there is no single locus operating
      in all families multiplex for SLE, and the degree of ethnic and genetic
      heterogeneity seems to be quite significant. In this respect, the genetics of SLE
      resemble those of many other complex genetic diseases. The list of candidate
      genes and pathways (see Table 1) implicated in the pathogenesis of SLE is
      expanding at a rapid rate. Understanding how alterations in these genes and
      pathways lead to the lupus phenotype is the primary objective of future genetic
      studies in SLE.

PMID- 11840694
TI  - Gene therapy for rheumatoid arthritis. Lessons from animal models, including
      studies on interleukin-4, interleukin-10, and interleukin-1 receptor antagonist
      as potential disease modulators.
AB  - Evidence from animal models convincingly supports the fact that gene therapy can
      be an advantageous strategy in the treatment of chronic destructive RA. In this
      article, we review the state of the art in anticytokine gene transfer into the
      synovial arthritic joint with the emphasis on IL-1Ra, IL-4, and IL-10 effects on
      CIA in mice. In CIA, only high and continuous release of IL-1Ra protein
      systemically by mini-osmotic pumps could prevent disease onset and was curative
      in mice. Local gene transfer seemed to be the obvious way to reach the high local
      levels that are demanded for protection. It was shown that local IL-1Ra
      overexpression reduced arthritis incidence and severity as well as tissue
      destruction. In line with observations about neutralizing antibodies and soluble
      receptors, gene therapy with TNF soluble receptors provided anti-inflammatory
      activity in early arthritis but not in advanced arthritis. The limited efficacy
      at later stages and poor protection against destruction imply that the
      combination of gene constructs for TNF and IL-1 inhibitors is the obvious
      direction for future therapy. Apart from targeting of proinflammatory cytokines,
      adenoviral overexpression of IL-10 and IL-4 may have therapeutic applicability.
      Local injection of AdIL-10 in the knee joint was effective at the site, but also
      highly reduced spreading to ipsilateral sites. High local dosages caused
      suppression in contralateral sites as well. The reports on the anti-inflammatory
      effect of AdIL-4 are conflicting; however, all present data showed that IL-4
      overexpression provides impressive protection against cartilage and bone erosion.
      Apart from the local effects in the injected joint, it is becoming more and more
      clear that local treatment also affects arthritis in nearby joints. This is an
      intriguing general finding, which may enlarge the therapeutic applicability of
      gene transfer in human arthritis. Proving the feasibility of gene therapy in
      experimental arthritis, most research efforts are now focused on improving local
      gene delivery by enhanced viral infection of synovial cells, using RGD-modified
      adenovirus, or achieving prolonged persistence and regulated expression with AAV.
      Elegant future alternatives are the application of in vitro engineered T cells as
      a vehicle capable of specific homing to joint tissues. The feasibility of viral
      transduction of chondrocytes to obtain a tissue-specific approach to treat
      articular cartilage damage in arthritis needs further attention.

PMID- 11840695
TI  - Transcript array analysis in rheumatology.
AB  - Transcript array analysis is a novel technique that examines the expression of
      thousands of genes simultaneously. Transcript array analyses are being used to
      clarify the diagnosis and prognosis of malignancies, and to understand the
      underlying pathogenesis of complex human disorders such as the rheumatic
      diseases. In this review, the authors will outline the use of transcript arrays
      to simultaneously assess gene activation of hundreds or thousands of genes, and
      their potential use in understanding and managing rheumatic disorders. The
      authors focus on the use of transcript arrays to confirm and refine disease
      diagnoses, to generate new hypotheses regarding pathophysiology of rheumatic
      diseases, and to the possible profiling of patients with respect to their likely
      response to therapies.

PMID- 11840696
TI  - Prognostic use of human leukocyte antigen genotyping for rheumatoid arthritis
      susceptibility, disease course, and clinical stratification.
AB  - HLA markers of the class II region are important for determination of the
      predisposition to RA, clinical manifestations, and rate of progression of joint
      destruction in this autoimmune disease. Furthermore, evidence emerges indicating
      that HLA markers also have an impact on treatment outcome in RA. Currently,
      several immunopathogenetic models of HLA-dependent influences in RA are under
      debate. These models insufficiently explain the graded influence of HLA-DR and
      HLA-DQ on manifestation and joint destruction, however. Currently, there is not
      enough evidence to unequivocally identify a primary susceptibility locus or to
      pinpoint the HLA-dependent mechanism in RA. Overall, the influence of HLA class
      II markers on disease susceptibility is rather restricted, and, in turn, their
      utility in establishing the diagnosis of RA is of limited use. Although relative
      risks are higher for the association of particular genotypes with extra-articular
      forms of RA, HLA genotyping may not contribute to prognostication in individual
      patients but may aid in disease stratification. In contrast, HLA genotyping in
      early RA, particularly when combined with the determination of RFs and
      determination of the presence of bony erosions, is of value to identify patients
      at risk for poor outcome. In turn, these patients may benefit from early
      aggressive therapy, and HLA genotyping should be useful to aid in risk
      stratification in patients and thus helpful for the choice of treatment. Lastly,
      disease and risk stratification based on HLA markers along with the elucidation
      of HLA-dependent mechanisms may facilitate the development of specific
      immunotherapy modalities.

PMID- 11840697
TI  - Genetic studies, clinical heterogeneity, and disease outcome studies in
      rheumatoid arthritis.
AB  - HLA haplotypes influence various clinical RA features considered to reflect
      severity in case-control and cohort studies. Of particular note is the fact that
      HLA generally influences the development of erosive and sometimes seropositive
      and nodular disease; in prospective studies, it noticeably affects joint surgical
      intervention. These are valuable clues indicating that HLA influences RA severity
      and chronicity. Nevertheless, HLA influences are generally weak enough so as to
      require large study subject numbers for detection. As a result, HLA genotyping
      has restricted usefulness for prediction of clinical severity in individual
      patients.

PMID- 11840698
TI  - The shared epitope and severity of rheumatoid arthritis.
AB  - After two decades of research involving thousands of RA patients, it is still not
      possible to precisely define the relation of HLA-DRB1 SE alleles to RA severity.
      Improvements in our understanding require more careful consideration of several
      factors such as ethnicity, gender, and the specific SE allele and genotype
      inherited. Large studies of heterogeneous groups of patients are required and
      indicate the need for collaborative efforts among researchers. In the interim,
      meta-analysis of the existing literature may provide some insight, because it
      allows utilization of the tremendous amount of research already completed. A
      preliminary meta-analysis highlighted the significant heterogeneity among the
      existing literature, and a more ambitious meta-analysis that uses individual
      patient-level data is currently ongoing. Profound implications exist for
      determination of the precise relationship between the SE and RA severity. This
      information could be valuable in identifying patients at greater risk of severe
      complications or as a stratification variable for clinical trials. Moreover,
      patients genetically predisposed to severe disease may benefit from early
      initiation of more aggressive therapy. Ultimately, clarification of the role of
      the SE may be valuable for the development of specific therapies directed toward
      DRB1 and related targets.

PMID- 11840699
TI  - The genetics of the target tissue in rheumatoid arthritis.
AB  - The genetic mechanisms that are complementary in predisposing and then
      establishing disease are yet to be fully elucidated. During a lifetime, the
      genetic composition of the host is not only hereditary but undergoes
      rearrangements, integrations, and more subtle single-base pair alterations. These
      changes can be inconsequential or lead to aberrant and deleterious pathologic
      changes. In a complex multifactorial disease such as RA, the relative roles of
      the dynamic versus germline elements of the disease have yet to be fully
      determined. Further studies of large populations are likely to segregate out
      factors affecting specific ethnic, clinical, and genetic subgroups.

PMID- 11840700
TI  - Genome studies and linkage in primary osteoarthritis.
AB  - Genetic epidemiologic studies have demonstrated that primary OA has a major
      genetic component that segregates in families in a complex manner. Some of these
      studies suggest that genetic susceptibility may be more relevant to female OA
      than to male OA and that genes may have a greater role in OA development and
      progression at certain joint groups compared with others. These observations are
      not universal, however, and discrepancies between different studies may simply
      serve to highlight the complex nature of the transmittance of OA susceptibility.
      The numerous OA linkage studies that have now been performed have revealed a
      number of regions of the human genome that are likely to harbor genes
      predisposing to OA. Several of these regions, particularly those identified in
      genome-wide scans of ASPs, have relatively low LOD scores; as a result, their
      reliability must be questioned. Nevertheless, a few of these regions have already
      been linked in more than one study, and these linkages can be considered as more
      robust. Such confirmation is a prerequisite to finer linkage mapping, which
      should narrow the linkage intervals to a point at which comprehensive association
      analysis of DNA sequence variants can be undertaken.

PMID- 11840701
TI  - Quality factors in interventional neuroradiology.
AB  - The interest we take in medical economics and strategy is like the one we take in
      politics: we may scorn politics, but it cannot be denied that it commands our
      entire life. For this reason, we must try to determine the conditions required to
      evaluate the quality of interventional neuroradiology, its operators, its
      practice, its advances, its teaching, and to maintain this quality. It is
      probably vital to the freedom of our future therapeutic decisions that we
      contribute effectively to this discussion before the standard is forced upon us
      by an exclusively economical or administrative logic. On the other hand, any
      advance can only be turned into progress if it is diffused and applied. There is
      no doubt that several levels of quality are acceptable, thus the best approach
      will be to look for and identify the minimum standard for quality or the limits
      of non-quality. We shall refrain from suggesting that the level of excellence at
      a given moment should be imposed upon all operators and constitute the standard
      level of practice. Practice is based on knowledge and competence. The most
      skilled surgical act cannot guarantee safe medical treatment if it is not
      supported by sufficient knowledge about the diseases and their symptoms.
      Mastership of the decision process requires a thorough vision of the therapeutic
      decision tree involved. Quality is a composition of global view and detailed
      analysis to allow a fuzzy gestion of the performance. Regardless of the plan
      chosen, openmindedness should be kept to allow adaptation, correction or
      interruption of a given therapeutic process in view of unpredicted pieces of
      information. Such input is a predictable possibility that should be explained to
      the patient prior to starting the procedure. Dealing with human beings, the
      attitude along with the technical management will be of paramount importance in
      the overall quality assessment.

PMID- 11840702
TI  - Minimally invasive neurosurgery.

PMID- 11840703
TI  - Quality management in neurosurgical nursing.

PMID- 11840704
TI  - Keeping track of critical incidents and complications.

PMID- 11840705
TI  - Principles of the morbidity and mortality conference.
AB  - The goals of the morbidity and mortality conference are learning from mistakes,
      recognising problems, and being aware of the risks of one's own procedures. Data
      are continuously collected, complications are classified, and the results of
      surgery are analyzed. By analysing and discussing the results every three months,
      total case mortality, mortality of specific procedures, incidence of haematomas,
      infection rate and incidence of thromboses and emboli are known and a continuous
      quality control is possible.

PMID- 11840706
TI  - Mechanisms to improve treatment standards in neurosurgery, cerebral aneurysm
      surgery as example.

PMID- 11840707
TI  - Techniques for hazard analysis and their use at CERN.
AB  - CERN, The European Organisation for Nuclear Research is situated near Geneva and
      has its accelerators and experimental facilities astride the Swiss and French
      frontiers attracting physicists from all over the world to this unique
      laboratory. The main accelerator is situated in a 27 km underground ring and the
      experiments take place in huge underground caverns in order to detect the
      fragments resulting from the collision of subatomic particles at speeds
      approaching that of light. These detectors contain many hundreds of tons of
      flammable materials, mainly plastics in cables and structural components,
      flammable gases in the detectors themselves, and cryogenic fluids such as helium
      and argon. The experiments consume high amounts of electrical power, thus the
      dangers involved have necessitated the use of analytical techniques to identify
      the hazards and quantify the risks to personnel and the infrastructure. The
      techniques described in the paper have been developed in the process industries
      where they have been to be of great value. They have been successfully applied to
      CERN industrial and experimental installations and, in some cases, have been
      instrumental in changing the philosophy of the experimentalists and their
      detectors.

PMID- 11840708
TI  - Mechanisms to improve teamworking in neurosurgery.
AB  - Team-working has been seen as an important essential in the delivery of modern
      medical care and quality. It should increase the range of skills and knowledge in
      dealing with clinical problems and needs to make better use of scarce
      professional resources. In addition many see the team as reducing the risk of the
      harmful consequences of idiosyncratic practice. Team-working requires a named
      consultant to be responsible for individual patients with corporate
      responsibility for the practice. Doctors and managers will need to work together.
      The structure of teams will by necessity change but the requirements are
      constant. These are to provide a basis for continuing professional development,
      the monitoring of standards of performance and capacity, and above all, to
      improve patient care and outcome. An essential prerequisite is the provision of
      resources to provide a supportive environment if clinical excellence is to be the
      norm.

PMID- 11840709
TI  - A complication conference for internal quality control at the Neurosurgical
      Department of the University of Heidelberg.
AB  - The registration of adverse events is an important issue in the field of
      medicine. Even today adverse event screening and registration is not part of the
      routine in most medical areas. In 1994, the Department of Neurosurgery at the
      University of Heidelberg implemented a conference for screening and registering
      adverse events. The aim was to record all complications occurring for an internal
      quality control. High priority was given to improving the process of data
      screening and registering. The conference is held every 2 weeks and all medical
      staff and residents of the department are obligated to be present. Screening of
      the adverse events encompasses all operations performed during a bi-weekly
      period. Every single operation is revised for an adverse event during or
      following the hospital stay. Adverse events are registered on a standardized data
      sheet and later transferred to a database for use in further investigations.
      After 6 years, the conference has been fully accepted and become an integral part
      of the workflow of the department. During this period, 8160 operations were
      screened and 1335 adverse events registered. The next step will be to integrate
      the data-collection process into the daily ward rounds using a personal digital
      assistant (PDA). This process is less time consuming and may perhaps augment the
      number of registered cases.

PMID- 11840710
TI  - Proficiency in neurosurgery.
AB  - This evaluation of proficiency is a comparison of other high performance
      occupations with neurosurgeons, an attempt to understand the minimal number of
      cases required for proficiency during both residency training and after, and the
      effect of human factors.

PMID- 11840711
TI  - Competency based residency training: the next advance in graduate medical
      education.

PMID- 11840712
TI  - The semi-annual residency rotation summary: a means to assess the quality of
      neurosurgical training.
AB  - The periodic evaluation of the progress made by the trainees is an adequate means
      for quality control of a training programme. The combination of the Neurosurgical
      Log-book and the new Evaluation Sheet allows a comprehensive assessment of the
      knowledge, progress, as well as the personal and professional development of the
      individual resident. Upcoming problems can be recognised at an early time point
      and be corrected immediately. With such periodic supervision the quality of
      training will improve with time and with experience.

PMID- 11840713
TI  - Continuing education--the EANS concepts.
AB  - Continuing Medical Education (CME) is becoming to be an important part of
      professional conduct of neurosurgeons in the member countries of EANS. It is
      therefore a task for the EANS to harmonize various systems of CME and to offer a
      compatible programme of continuing education that would meet the expectations and
      needs of the neurosurgeons. It should help choose fields in which updating
      knowledge is indispensable, offer teaching and training opportunities and provide
      systems of evaluation and certification of progress in neurosurgical CME.

PMID- 11840714
TI  - Continuing education: the British experience.
AB  - The methods used to assess proficiency in neurosurgical trainees and consultant
      staff are reviewed. Under the auspice of the Surgical Royal Colleges trainees
      undergo a formal assessment 6 monthly by their trainer, annually by a local
      training committee and in their 3rd year of training by the Specialist Advisory
      Committee (SAC) in Neurosurgery. This committee supervises all neurosurgical
      training in the UK and Ireland and recommends trainees for the Certificate of
      Completion of Training if their training assessments and operative experience are
      satisfactory and if they have passed the Intercollegiate Specialty Examination in
      Neurosurgery. Assessing proficiency of consultant staff in the UK poses greater
      difficulty. For several years neurosurgeons have registered Continuing Medical
      Education (CME) credits on a voluntary basis. Such action is insufficient to
      reassure the public of professional competence. The General Medical Council (GMC)
      have submitted proposals for revalidation based on- (i) the maintenance of a
      'folder' including details of performance, CME and complaints, (ii) annual
      appraisals carried out internally, (iii) a 5 yearly external assessment which if
      satisfactory would lead to revalidation by the GMC. Team working will be
      encouraged and consultants made responsible for the quality of service of their
      professional colleagues. A national comparative audit of subarachnoid haemorrhage
      should permit comparison of outcomes between neurosurgical units.

PMID- 11840715
TI  - Is there a need for periodical recertification?

PMID- 11840716
TI  - How to control the risk of novel surgical procedures.
AB  - Novel surgical procedures impose particular problems in addition to the general
      issues of clinical research [1, 7]. Surgical procedures are usually highly
      technical and therefore difficult to judge by the institutional ethics committee.
      The ethics committee has therefore to rely on external experts and a relatively
      large responsibility remains with the surgeon in charge. There are no generally
      valid regulations regarding new surgical procedures. At our institution, informed
      consent by the patient, a detailed risk analysis, testing and training in the
      anatomy/animal lab are required, and in addition a formation/training visit if
      know-how is available elsewhere. In emergency situations, if during a procedure
      circumstances call for a new surgical procedure, all the above preconditions
      cannot be met. A suggested minimum requirement in such a situation is that the
      decision for a new procedure is achieved by agreement of two board certified
      specialists. A problem that has to be solved in the future is how to make the
      negative experiences with new surgical procedures generally available in order to
      prevent that the same mistakes are repeated in other institutions.

PMID- 11840717
TI  - Measuring the importance of scientific results--in neurosurgery.

PMID- 11840718
TI  - Learning from errors in aviation.

PMID- 11840719
TI  - Quality management in hospitals--quo vadis?

PMID- 11840720
TI  - How can the ISO 9000 concept be applied to neurosurgery?

PMID- 11840721
TI  - Introduction of ISO 9000 and other quality concepts applied to neurosurgery.

PMID- 11840722
TI  - "Emerging unwanted side effects of quality control, or the value of the
      immeasurable qualities of medical care".
AB  - The author reviews briefly the sociocultural aspects of the quality control
      movements and how they relate to the medical profession. The "ethos" of the
      neurosurgical practice and the way to harmonize the new paradigms of modern
      medicine and the need to define parameters to evaluate quality are discussed.

PMID- 11840723
TI  - Ethics and quality of neurosurgical care.

PMID- 11840724
TI  - Research and clinical routine in the next century, segregation or cooperative
      networks?

PMID- 11840725
TI  - Guidelines for guidelines.
AB  - Clinical practice guidelines (CPGs) are suited tools for controlling and
      improving the effectiveness and efficiency of medical care. With the upcoming
      internet, the numbers of CPGs have increased rapidly, however, only few offer the
      attributes of good guidelines such as reliability/reproducibility, applicability,
      flexibility, clarity, multidisciplinary process, scheduled review and
      documentation of clinical and scientific evidence. Nearly identical criteria for
      appraisal of CPGs have been developed in many countries consisting of a checklist
      with questions concerning the quality of development, the content and format, and
      the applicability of the guideline. In the United States, guidelines which
      successfully passed the appraisal (or clearing) process, were stored in the
      National Guideline Clearinghouse, an internet-based database. A German
      counterpart is under construction, which will comprise clearing reports reviewing
      and appraising all existent guidelines covering a medical topic. Developing high
      quality CPGs is a time consuming and expensive process. A widely accepted
      guideline for guideline development was published by the Scottish Intercollegiate
      Guideline Network. CPGs touching neurosurgical topics are rare and often
      developed without neurosurgical participation. Due to the potential medico
      economic impact of CPGs in the future, national neurosurgical societies and their
      international associations should play a more active role in the development and
      implementation of CPGs.

PMID- 11840726
TI  - Safety of novel projects, the battle against Murphy's law.
AB  - With great pleasure and respect I have accepted the offer to speak in this
      congress. Medicine was a dream for me sometime ago and my second choice for
      studies. I remained with my first choice engineering and I am still happy with
      it; but I never forgot my love and enthusiasm for medicine. My career brought me
      in contact with many countries and technologies, but the development towards
      safety management became a dominant trend. At CERN I am a Group Leader in Matters
      of Safety for the Compact Muon Solenoid (CMS) experiment. In the last few years
      my attention has been increasingly focused on human and institutional safety
      aspects, besides the technical ones. My paper deals with three major topics:
      Safety management at CERN-CMS Murphy's law and the growing importance of
      institutional and human factors in safety Future outlook for safety and
      conclusions. In the conclusions the commonalities between different technologies
      become more evident as the importance of the human nature and man's role and
      enticement to actively and intelligently contribute to safety are presented.
      Based on experience and references an appeal is launched to pay more attention to
      the human factor in safety and recognize the rules and regularities of human
      behaviour in order to better combat Murphy's law.

PMID- 11840727
TI  - Principles of risk and safety.
AB  - Studies of error and adverse events in medicine have brought a growing awareness
      of the extent of harm to patients. The psychology of human error strongly
      suggests that individual liability to error is strongly influenced by the
      conditions and organisation of the working environment and the nature of the
      task, in particular the complex and inherently uncertain judgements frequently
      made in medicine. Research into accidents in medicine and other high risk areas
      has lead to a much broader concept of causation, with less focus on individuals
      and more on pre-existing organisational factors. These ideas have been adapted to
      practical use in healthcare in the analysis of adverse events and in working
      towards developing safer systems of care. The final section of the paper
      summarises the implications of this approach for healthcare in terms of an
      overall systems approach, the need for basic information about clinical
      incidents, the benefits of systematic investigation and analysis, the nature of
      safety interventions, the need to study success as well as failure and the need
      to develop an open, safety aware culture in healthcare.

PMID- 11840728
TI  - The psychology of team interaction.
AB  - This paper aims to review psychological research results and methods which might
      be relevant to the issue of team interaction in the medical domain. The complex
      research on team performance is coherently organized into a proposed framework
      focussing in detail on task and social orientations of interacting team members.

PMID- 11840729
TI  - Crew coordination in aviation.

PMID- 11840730
TI  - Principles of quality management in medicine: the British concept.
AB  - The National Health Service in Great Britain is undergoing radical change
      particularly with regard to clinical governance, self-regulation, revalidation,
      career structures and training and patterns of healthcare delivery. All these
      changes are relevant to risk-control and quality management. This review surveys
      these generic changes and illustrates the implications for neurosurgery.
      Neurosurgery in the UK has the opportunity to enhance their patients care by
      expanding the number of consultants, developing further sub-specialisation and
      enhancing its training and review and dissemination programmes but only if extra
      resources are provided.

PMID- 11840731
TI  - Quality assurance in neurosurgery: United States concepts.
AB  - At present, quality assurance in United States neurosurgery is based primarily on
      neurosurgeons meeting requirements for certification by the American Board of
      Neurological Surgery and residency training programs meeting requirements for
      approval by the neurosurgical Residency Review Committee. These organizations,
      plus a number of other private, autonomous, physician directed groups have
      assumed responsibility for assuring neurosurgical quality. There are, however, no
      reliable data that such processes are effective and it is likely that
      neurosurgical quality assurance will move toward outcomes based documentation in
      the future. This article presents a brief review of the concepts of quality
      assurance and assessment as they are applied in the healthcare system of the
      United States. A more detailed review of the process of neurosurgical
      credentialing is also presented and a paradigm for evaluating and improving
      neurosurgical quality is proposed. It must be clearly stated that the opinions
      expressed in this article are those of the author and do not represent the
      official position of any neurosurgical organization.

PMID- 11840732
TI  - Principles and problems of assessing the results of medical treatment.
AB  - The integration of clinical expertise with the best available evidence from
      systematic research is the foundation of evidence-based medicine (EBM). The
      results from a well-designed randomised controlled trial (RCT) is regarded as the
      best evidence on which to base treatment. In neurosurgical practice fewer
      treatments are based on the results of RCTs than in medical practice. The reasons
      are historical, ethical, practical and can be compounded by the surgical learning
      curve. In neurosurgical practice treatment protocols and surgical indications
      vary widely. In addition there is a lack of patient orientated, disease specific
      and generic outcome measures. However, it is a neurosurgical responsibility to
      provide hierarchical evidence upon which treatment can be based. Comparative
      audit may offer a solution provided there is high quality data collection,
      relevant measures of outcome, a defined case-mix and a representative population.
      Comparative audit can produce bias but neurosurgeons will need to meet the
      challenge of EBM. Their patients will expect it.

PMID- 11840733
TI  - Impacts of socio-economic restrictions on quality in neurosurgery and other
      specialities.

PMID- 11840734
TI  - Quality, risk and health care: another view.

PMID- 11840735
TI  - Quality management in neuropathology.
AB  - Quality management will have an increasing impact on the field of clinical
      neurosciences. The neuropathological examination of surgical or autopsy samples
      obtained from the central nervous system (CNS) and related structures,
      cerebrospinal fluid, peripheral nerve or skeletal muscle serves three major
      purposes: to identify a structural correlate of the disease, provide a reliable
      basis for treatment strategies and to investigate underlying pathogenic
      mechanisms. In order to achieve histopathological diagnosis at a consistent
      quality, quality management and control have to be implemented at different
      levels. At the local site, these concern neuropathological services, such as
      acquisition of tissue specimens, handling and staining procedures as well as
      diagnostic examination. Training programs offered in slide seminars and
      diagnostic workshops are important tools to highlight new developments and
      maintain high standards. National reference centers for brain tumors,
      neurodegenerative disorders, prion or muscle and nerve diseases assist with a
      second opinion in difficult cases and support epidemiological as well as clinical
      therapy trials. An international panel of neuropathologists has established
      guidelines for the classification of brain tumors, recently updated during a WHO
      2000 consensus conference. Finally, the standardized histopathological and
      cytological diagnosis of CNS disorders plays also an important role in providing
      quality control for associated fields of the clinical neurosciences, such as
      neuroradiology, neurology, psychiatry and neurosurgery.

PMID- 11840736
TI  - Quality management in laboratory medicine.
AB  - In the context of total quality management the paper is focused on analytical
      quality with special emphasis on the preanalytical steps from the patient to the
      sample. At the present time those are the most important limiting factors of the
      quality of laboratory results.

PMID- 11840737
TI  - Patient information in the light of quality assurance.
AB  - The relationship between patients and doctors has markedly changed over the last
      century. While until the turn of the 19th/20th century the patient was considered
      an object upon whom the doctor had the right to exert his art, the patient was
      then thought to have an integrity which the doctor could only legally injure with
      the consent of the patient. This was reflected in many court rulings, e.g. in
      Germany in 1894, requesting a doctor to inform the patient about therapy before
      performing surgery or even before giving medication, but also before performing
      invasive diagnostic procedures. The intensity of information required by
      law/court to be given to the patient varies also over time. Details of the
      implications to today's medical treatments are discussed.

PMID- 11840738
TI  - What diagnostics are necessary before and after surgery?

PMID- 11840739
TI  - Standards of neurosurgical procedures.
AB  - Written specifications with regard to procedures performed, equipment used, and
      training of the involved personnel are widely used in the industry and aviation
      to guarantee constant quality. Similar systems are progressively being introduced
      to medicine. We have made an effort to standardize surgical procedures by
      introducing step-by-step guidelines and checklists. The current experience shows
      that a system of written standards is applicable to neurosurgery and that the use
      of checklists contributes to the prevention of forgetting essential details.
      Written standards and checklists are also a useful training tool within a
      university hospital and facilitate communication of essentials to the residents.
      Comparison with aviation suggests that standardization leads to a remarkable but
      nonetheless limited reduction of adverse incidents.

PMID- 11840740
TI  - Standards of neuroanesthesia.
AB  - Currently there are no published standards of neuroanesthesia. However, consensus
      guidelines based on physiological considerations, published literature, clinical
      experience and expert opinions do exist. Four areas of the practice of
      neuroanesthesia: premedication, intraoperative algorithms, emergency algorithms,
      and postoperative care of the neurosurgical patient will be reviewed.

PMID- 11840741
TI  - Towards European standards in neuroradiology.

PMID- 11840742
TI  - [Pay attention to prevention and treatment of glucocorticoid glaucoma].

PMID- 11840743
TI  - [Nonperforating trabecular surgery with reticulated hyaluronic acid implant].
AB  - OBJECTIVE: To evaluate the clinical results of nonperforating trabecular surgery
      (NPTS) with reticulated hyaluronic acid implant. METHODS: Twenty cases (28 eyes)
      of advanced open angle glaucoma (C/D = 0.86 +/- 0.14) underwent NPTS with
      reticulated hyaluronic acid implant. Postoperatively, the intraocular pressure
      (IOP), intraocular reactions and the bleb appearance were recorded, gonioscopy
      and ultrasound biomicroscopy were performed. RESULTS: The mean follow-up was (9.2
      +/- 3.4) months. The mean IOP was (28.1 +/- 10.2) mm Hg preoperatively and (17.5
      +/- 4.1) mm Hg postoperatively, the difference being significant (t = 5.776, P <
      0.001). The number of drugs used for anti-glaucoma was (2.04 +/- 0.74)
      preoperatively, and (0.71 +/- 0.71) postoperatively (t = 8.103, P < 0.001). On
      the last visit, in 27 eyes (96.4%) the IOP was < or = 21 mm Hg, and among them,
      there were 12 eyes (42.8%) without anti-glaucoma medicine and 15 eyes with anti
      glaucoma medicine. In 13 eyes (46.4%) the IOP was decreased > or = 10 mm Hg in
      which 6 eyes did not take any anti-glaucoma medicine and 7 eyes used anti
      glaucoma medicine. There were no flare and cells in the anterior chamber in 14
      eyes. In 10 eyes there was only slight flare that disappeared in 2-6 days. In 4
      eyes there was a small amount of hyphema that was absorbed in 3-7 days. After
      operation, there was an obvious diffuse bleb in each eye, at the last visit,
      there were functional blebs in 19 eyes, the successful filtration was ceased in 9
      eyes within 1.5-3 months. Intra-operatively, in 5 eyes microperforations occurred
      in the trabecular meshwork without iris prolapse, and after operation, under the
      gonioscope, the perforation could be observed in 3 eyes. In another 4 eyes, there
      was no intra-operative perforation, but a small fissure was seen by gonioscopy.
      In the post-operative 1-8 months, ultrasound biomicroscopy was performed, and it
      was shown that the implant was not degraded. CONCLUSIONS: The elevated IOP in
      patients with open angle glaucoma can be effectively reduced by NPTS, and the
      number of drugs used for anti-glaucoma was decreased. The post-operative
      complications were much less because of no intra-operative penetration of the
      anterior chamber. Therefore, NPTS is a very hopeful and practicable new anti
      glaucoma surgery.

PMID- 11840744
TI  - [Glaucoma seton implantation surgery via different pathways for complicated
      glaucoma].
AB  - OBJECTIVE: To evaluate the effectiveness of glaucoma seton implantation surgeries
      via three different pathways for complicated glaucoma. METHODS: Ninety-nine cases
      (99 eyes) with complicated glaucoma having undergone glaucoma seton implantation
      surgeries were divided into three groups. Fifty-eight cases were included (58
      eyes) in the group with anterior chamber implantation (AC group), 16 cases (16
      eyes) were in the group with posterior chamber implantation (PC group) and 25
      cases (25 eyes) were in the group with vitreous cavity implantation (VC group).
      RESULTS: The follow-up ranged from 6 to 34 months (mean 19.6 months). In the AC
      group, the postoperative intraocular pressure (IOP) of 40 cases (69.0%) was < 21
      mm Hg (1 mm Hg = 0.133 kPa) without using any pressure-lowering agents. The
      postoperative IOP of 6 cases (10.3%) was < 21 mm Hg with pressure-lowering
      agents. Patients with IOP controlled < 21 mm Hg were altogether 46 cases (79.3%).
      The IOP of 11 cases (68.8%) in the PC group was controlled without agents and
      another 1 case (6.2%) was controlled with medications. Therefore, the total
      success rate was 75.0% (12 cases). The corresponding rates for the VC group were
      10 cases (40.0%), 3 cases (12.0%) and 13 cases (52.0%) respectively. Statistical
      significant difference (chi 2 = 6.525, P = 0.038) was found in the success rates
      among these 3 groups. But if we excluded cases with neovascular glaucoma, no
      statistical difference (chi 2 = 4.231, P = 0.121) was found of the success rates
      among these 3 groups. CONCLUSION: No influence on surgical effectiveness was
      found among glaucoma seton implantation surgeries via different pathways for
      complicated glaucoma.

PMID- 11840745
TI  - [Evaluation of optic disc in open-angle glaucoma with hemifield defect by
      Heidelberg retinal tomography].
AB  - OBJECTIVE: To investigate whether the glaucomatous optic disc change demonstrated
      by Heidelberg retinal tomography (HRT) is consistent to the distribution of the
      visual field defects and whether Heidelberg retinal tomography, (HRT) parameters
      in primary open angle glaucoma (POAG) and normal tension glaucoma (NTG) are
      different. METHOD: Sixty-four eyes of 64 patients with open angle glaucoma (27 of
      POAG, 37 of NTG) and hemifield abnormality detected by Humphery Field Analyzer
      (HFA) were tested by HRT. The HRT parameters and the visual field results were
      divided into two parts (0 degree-180 degrees and 180 degrees-360 degrees) for the
      corresponding analysis. RESULTS: Comparing with the half disc corresponding to
      the intact hemifield, the half disc corresponding to the defective hemifield has
      significantly higher values of cup/disc area ratio and cup shape measure, but has
      significantly lower values of rim area, the thickness and cross-section area of
      the retinal nerve fiber layer. No significant differences were found between NTG
      and POAG eyes in the HRT parameters of the half disc corresponding to the
      defective hemifield. CONCLUSIONS: The optic disc changes detected by HRT are
      consistent to the distribution of the visual field defects, cup/disc area ratio,
      cup shape measure, rim area, mean thickness and cross-section area of the retinal
      nerve fiber layer, and they are the relatively sensitive parameters. That the HRT
      parameters of NTG and POAG are similar suggests they possibly have certain
      similar mechanisms in the development of glaucomatous neuropathy.

PMID- 11840746
TI  - [Muscarinic receptor subtype-3 expression in trabecular meshwork of normal human
      eye and primary open-angle glaucoma].
AB  - OBJECTIVE: To identify the muscarinic receptor subtype-3 (M3-receptor) expression
      in trabecular meshworks (TM) of normal human eyes and eyes with primary open
      angle glaucoma (POAG) and discuss the pathological changes of TM in POAG. METHOD:
      TM specimens were taken from 5 normal persons and 10 patients with POAG at late
      stage. Then LSAB immunohistochemical technique was used to identify M3-receptors.
      The results were observed under microscope and compared with computer-image
      analysis system. RESULTS: (1) The trabecular meshwork cells in all the 5 normal
      persons expressed M3-receptors. The positive cells mainly existed in the uveal
      part of TM, from Schwalbe's line to scleral spur. (2) In TM from eyes with POAG,
      the amount of both TM cells and M3-receptor positive cells were reduced
      obviously, even some specimens had no such positive expression. The positive
      cells were correspondingly decreased in number and scattered in distribution.
      CONCLUSION: The TM cells in normal human eyes express M3-receptors. The TM cells
      and M3-positive cells in eyes with late POAG are reduced in number and their
      distribution is irregular.

PMID- 11840747
TI  - [Vitreoretinal surgery with intraocular C3F8 tamponade for retinal detachment due
      to macular hole without face-down positioning].
AB  - OBJECTIVE: To evaluate the effectiveness of vitreoretinal surgery with 16%
      perfluoropropane (C3F8) tamponade without face-down positioning in treatment of
      retinal detachment due to macular hole. METHODS: Twenty-seven consecutive eyes in
      27 patients with retinal detachment due to myopic macular hole underwent closed
      vitrectomy, membrane peeling, gas-fluid exchange with C3F8 tamponade in the whole
      vitreous chamber. In 3 eyes, phacoemulsification was performed, and 2 of them
      received intraocular lens implantation. Postoperatively, except avoiding the
      supine position, the body position was not restricted. RESULTS: Twenty-one cases
      (78%) obtained successful retinal reattachment without the postoperative face
      down positioning. In another 6 cases, because of the relatively quick absorption
      of the gas, the white macular hole and the subretinal proliferation, the
      operation was not successful, the hole being not sealed and the retinal
      detachment at the lower part still existing. In the 3 cases with quick absorption
      of the gas, on the 10th day after the operation, the body position was changed
      into a face-down one. In 2 of them, the retinal reattachment occurred. After > 6
      months of follow-up, the retinal reattachment remain the same in 22 cases (81%),
      the macular hole was healed, and the visual acuity was elevated to > or = 0.1 in
      19 cases. The main complications were lens opacity in 6 cases (31%), temporary
      elevation of intraocular pressure in 3 cases (11%). CONCLUSION: Use the methods
      for the treatment of macular hole and retinal detachment mentioned above may
      obtain relatively good therapeutic results, particularly suitable for senile and
      unhealthy cases.

PMID- 11840748
TI  - [The morphologic structure of vitreous hemorrhage and posterior vitreous
      detachment].
AB  - OBJECTIVE: To investigate the morphologic structures of vitreous hemorrhage that
      may be beneficial to its treatment. METHODS: The clinical data of 74 cases (79
      eyes) with vitreous hemorrhage resulting from proliferative diabetic retinopathy,
      retinal vasculitis and retinal vein occlusion in December 1995 to January 2000
      and having undergone vitrectomy were studied retrospectively, which focused on
      the morphologic characteristics of vitreous body by B-scan, surgical microscopy
      and surgical manipulation, to evaluate the relation of retina and vitreous body
      in order to discern the relationships among the retina, neovascular fibromembrane
      and the posterior hyaloid surface. RESULTS: Posterior vitreous detachment (PVD)
      in various degrees was observed in all the cases. The morphologic character was
      classified as the complete and partial vitreous detachment. The latter one can be
      subdivided into "V", "L" types and posterior vitreoschisis that was not rarely
      seen in the proliferative phase of ischemic retinopathy. CONCLUSIONS: To evaluate
      the characteristics of posterior vitreous detachment and vitreoschisis may
      provide valuable information for vitreoretinal surgery, elevate the rate of
      success and improve the prognosis of the surgery.

PMID- 11840749
TI  - [Phacofragmentation of dislocated lens in vitreous cavity].
AB  - OBJECTIVE: To discuss the surgical techniques and therapeutic effects of
      phacofragmentation of the dislocated lens in the vitreous cavity. METHODS:
      Phacofragmentation was performed on 23 eyes of 23 patients with dislocated lens
      or subluxated lens in the vitreous cavity. With high suction and moderate
      ultrasound, the nucleus could be emulsified. Energy and time of emulsification:
      50%-60% of energy was set up and emulsification spent 43 s to 3 min 23 s (mean 1
      min 57 s). The pressure of maximum vacuum aspiration was 110-120 mm Hg (1 mm Hg =
      0.133 kPa). In 11 eyes, anterior chamber intraocular lens (ACIOL) was implanted.
      Cryoapplications and encircling procedure were also performed on one eye.
      RESULTS: Phacofragmentation was successful in all patients. After follow-up for 5
      19 months (mean 7.2 months), the corrected visual acuity was obviously improved
      in the cases of ACIOL and Marfan's syndrome, with 12 patients achieving visual
      acuity of 0.12-0.6. The major complications were corneal edema and damage of
      iris. CONCLUSIONS: It is demonstrated that phacofragmentation in the central
      vitreous cavity is safe and fairly easy procedure without adverse effects on
      retina and sclera. It helps to reduce intraoperative risks of alternative
      methods, avoiding a large opening of the anterior chamber and hypotony of the
      globe.

PMID- 11840750
TI  - [A clinical report on hydrophilic acrylic foldable lens implantation].
AB  - OBJECTIVE: To investigate the therapeutic effects of hydrophilic acrylic foldable
      lens implantation. METHODS: This prospective randomized placebo-controlled study
      comprised 214 eyes of 190 patients after phacoemulsification. The hydrophilic
      acrylic foldable lens was implanted in group 1 (114 eyes), and the PMMA
      intraocular lens (IOL) implanted in the control group 2 (100 eyes). Within the 3
      6 month follow-up period, the changes of visual acuity, corneal astigmatism and
      endothelial cells, the location of IOL and the degree of posterior capsular
      opaqueness postoperatively between the two groups were compared. RESULTS: The
      visual acuity of group 1 was significantly better than that of group 2 within 3
      days postoperatively (P < 0.05), but there was no statistically significant
      difference after 3 months. The surgically induced astigmatism, incidents of
      posterior capsular opaqueness and subluxation of IOL of group 1 were
      significantly lower than that of group 2 after 3 months postoperatively (P <
      0.05). The comparison of the endothelial cell loss ratio between the two groups
      was not significantly different (P > 0.05). CONCLUSION: The hydrophilic acrylic
      foldable IOL is easy to handle during implantation, highly biocompatible in the
      eyes, with less postoperative inflammatory reactions and shorter recovery period,
      and may provide satisfactory therapeutic effects.

PMID- 11840751
TI  - [The black diaphragm intraocular lens implantation].
AB  - OBJECTIVE: To evaluate the clinical effect of the black diaphragm intraocular
      lens (IOL) implantation. METHODS: The black diaphragm IOL implantation performed
      on 23 cases (23 eyes) of traumatic aniridia (21 eyes) and congenital aniridia (2
      eyes) was studied retrospectively. RESULTS: Photophobia was reduced obviously and
      the naked visual acuity was improved in all 23 cases after the black diaphragm
      IOL implantation, VA > or = 0.1 in 16 cases (70%). The complications included
      vitreous hemorrhage (2 eyes) in the operation, and there were exudates on the
      surface of IOL (13 eyes), IOP elevation (3 eyes), macular hole (1 eye), recurrent
      retinal detachment (1 eye) and corneal decompensation (5 eyes) after the
      operation. CONCLUSION: The black diaphragm IOL implantation provides an effective
      means of treating traumatic or congenital aniridia, but the indication should be
      strictly controlled.

PMID- 11840752
TI  - [The investigation with contrast sensitivity after implantation with UV and UVCY
      types of intraocular lens].
AB  - OBJECTIVE: To research the difference in vision after UV and UVCY two types of
      intraocular lens implantation (The light 380-790 nm may transmit through the UV
      lens, and the UVCY lens may partly filter the light < 640 nm including part of
      the light < 460 nm.). METHODS: MCT 8000 contrast tester was used in the
      postoperative two months. RESULTS: The contrast sensitivity of the patients with
      UVCY lenses was superior to that with UV lenses obviously (P < 0.05) under the
      condition of glare and 3 c/d, 6 c/d space frequency. CONCLUSION: The UVCY lens is
      more advantageous to improve visual function.

PMID- 11840753
TI  - [Phacoemulsification for short eye axis cataract].
AB  - OBJECTIVE: To analyze the operative difficulty of cataract phacoemulsification in
      an eye with shorter axial length and discuss its preventive measures. METHODS: A
      retrospective study was performed to analyze the 122 patients (143 eyes) who had
      undergone cataract phacomulsification. Their ocular axial lengths were 20.21 to
      22.10 mm. RESULTS: Because these patients had shorter ocular axis, shallower
      anterior chamber depth, narrower space in the anterior ocular segment and higher
      vitreous pressure, the operation was hard to perform. The rate of posterior
      capsular rupture was 7.69%. The postoperative inflammatory reaction was severe.
      The rate of reversible corneal edema (29.37%) was obviously higher than that in
      cataractous eyes with normal ocular axis (6.7%, P < 0.01), and also higher than
      that in eyes with normal ocular axis and hard nucleus (12.5%, P < 0.05).
      CONCLUSIONS: It is emphasized that the correct technique of incision, application
      of chopping and breaking nucleus technique, lower energy and higher aspiration
      for effective phacoemulsification with the help of Viscoat viscoelastic material
      and maintenance of deep anterior chamber are the key procedures to obtain
      satisfactory operative results.

PMID- 11840754
TI  - [Orthokeratology induced infective corneal ulcer].
AB  - OBJECTIVE: To investigate the clinical course, treatment and outcome of infective
      corneal ulcer induced by orthokeratology. METHODS: Sixteen cases of infective
      corneal ulcer caused by orthokeratology were reported, including 7 cases of
      pseudomonas corneal ulcers, 8 cases of acanthamoeba keratitis and 1 case of
      mycotic keratitis. Smears and cultures from corneal scrapings for bacteria, fungi
      and amoeba were performed for all of the patients. According to the results of
      pathogenic microorganisms, different therapeutic approaches were given. Lamellar
      keratoplasty or penetrating keratoplasty was performed for 9 patients whose
      corneal lesions were serious and unresponsive to medical therapy. RESULTS: After
      medical treatment or keratoplasty, corneal infections of all the patients were
      controlled. The visual acuity of most cases was improved. CONCLUSIONS: The
      infective corneal ulcer is the most serious complication of orthokeratology. The
      treatment of infective corneal ulcer should be directed toward the elimination of
      the pathogenic microorganisms from the cornea. Keratoplasty continues to have a
      central role in the management of some advanced cases. Although the infections
      can be controlled, the vision of these patients is seriously damaged.

PMID- 11840755
TI  - [The value of color Doppler imaging ultrasound in diagnosis of orbital diseases].
AB  - OBJECTIVE: To study the useful value of color Doppler imaging (CDI) ultrasound in
      the diagnosis and differential diagnosis of orbital diseases. METHODS: By using
      the technique of CDI ultrasound, 288 cases with orbital diseases were examined to
      show color Doppler flow imaging and pulsed wave Doppler (PWD) spectrum. RESULTS:
      Among 288 cases of the orbital diseases, 38 cases of malignant tumors and 23
      cases inflammatory pseudotumors showed the signals of blood flow. From CDI
      ultrasound examination, there were 18 in 23 cases with benign mixed tumors of the
      lacrimal gland showing artery blood flow and 22 in 28 cases with neurilemoma
      showing signals of blood flow. No blood flow was obtained in 62 among 74 cases
      with cavernous hemangioma, in 16 cases of dermoid cysts or epidermoid cysts and 1
      case of lipoma. From CDI, rich blood flow was seen in 4 and scarce in 3 cases
      with meningioma, and in 6 cases of optic nerve gliomas, there were 5 cases
      without any blood flow signals. Other 2 cases with benign hemangioendothelioma, 2
      hemangiopericytoma and 1 neurofibroma showed rich or scarce blood flow signals.
      Among 29 cases of venous hemangiomas, 16 cases showed venous flow. Three cases
      with arteriovenous aneurysms showed artery blood flow in the CDI. Fifteen cases
      with varicosis exhibited a dynamic blood flow changes in the CDI. Six cases with
      infantile hemangioma, the decreased blood supply was shown in the CDI after
      treatment. In the thirteen cases with carotid artery cavernous sinus fistula,
      including 8 cases of internal carotid artery cavernous sinus fistula (CCF) and 5
      dural cavernous sinus fistula (DCF), dilated superior ophthalmic vein (SOV) with
      arterialized blood flow was seen. In the mean time, PWD showed that the SOV of
      CCF had a higher velocity and a higher flow volume than that of DCF, while its
      resistance index was lower than that of the DCF. In 1 case with thrombophlebitis,
      its SOV showed dilated superior ophthalmic vein without blood flow. CONCLUSIONS:
      CDI can provide the information of color blood flow in orbital diseases,
      especially the tumors with rich vascular tissue and orbital vascular diseases. It
      is important in the diagnosis and differential diagnosis of the orbital diseases
      in combination with B-mode ultrasound, CT or MRI.

PMID- 11840756
TI  - [A study on expression of CD44V6 and PCNA in squamous cell carcinomas].
AB  - OBJECTIVE: To investigate the expression of cluster of differentiation 44 variant
      6 (CD44V6) and proliferating cell nuclear antigen (PCNA) in squamous cell
      carcinomas (SCC) in eyes. METHOD: Streptavidinbiotin peroxidase complex (SABC)
      immunohistochemical method was used to study the expression of CD44V6 and PCNA in
      35 cases with squamous cell carcinoma in eyes, 20 cases with papilloma, 11 cases
      with normal eyelid tissue. RESULTS: The CD44V6 positive rate was 62.9% (22/35) in
      squamous cell carcinomas in eyes, 15.0% (3/20) in papillomas, none in 11 cases
      with normal eyelid tissue. The positive expression rate of CD44V6 in the
      malignant group was significantly higher than that in the benign and control
      group, and the positive expression rate of CD44V6 in cases with metastasis was
      significantly higher than that without metastasis. PCNA labeling index (PI) in
      the CD44V6 positive expression of tumors was significantly higher than that in
      the CD44V6 negative expression of tumors (t = 20.21, P < 0.01). CONCLUSIONS: The
      over-expression of CD44V6 is correlated with the progress and metastasis of SCC.
      CD44V6 protein expression is correlated positively with PCNA expression, and the
      evaluation of both CD44V6 and PCNA is useful for predicting the prognosis.

PMID- 11840757
TI  - [The relation between expression of basic fibroblast growth factor and mast cells
      in pterygium].
AB  - OBJECTIVE: To examine the expression and distribution of basic fibroblast growth
      factor (bFGF) and mast cells in pterygium, and evaluate its effects in the
      pterygium formation and progression. METHOD: The expression of bFGF and mast cell
      tryptase in 17 primary pterygia, 6 recurrent pterygia and 6 normal conjunctival
      specimens were studied. The mast cell count and bFGF expression situation were
      observed. RESULTS: The bFGF was specifically localized in the epithelium, blood
      vessels and a subset of connective tissue cells. The bFGF expression was
      increased in the recurrent pterygium. The numbers of infiltrating mast cells
      (five 400 x sights) were (45.47 +/- 5.50) cells and (48.83 +/- 3.19) cells in the
      primary and recurrent pterygium respectively. In the comparisons between the
      cells in the pterygium (primary and recurrent) and (4.24 +/- 2.36) cells in the
      normal connective tissue, there were significant differences (F = 200.3128; q =
      26.6762, 23.7341; P < 0.05). The shape and distribution of all the tryptase
      positive cells (mast cells) in the pterygium tissues were similar to that of the
      cells with bFGF expression in the connective tissue. And the majority of bFGF
      positive cells (87.54 +/- 3.60)% were similar to that of mast cells in the
      connective tissue. CONCLUSIONS: All infiltrating mast cells in pterygium have
      bFGF-positive expression. The bFGF expression is increased in the epithelium,
      blood vessels and infiltrating mast cells of the pterygium, and may contribute to
      the formation and progression of a pterygium.

PMID- 11840758
TI  - [The change of tear secretion and tear film stability in castrated male rabbits].
AB  - OBJECTIVE: To evaluate the effect of androgen on tear secretion and tear film
      stability by observing the changes of ocular surface and tear film in the
      castrated male rabbit. METHODS: Sixteen male rabbits were selected and randomly
      divided into the normal control group (8 rabbits) and the castrated group (8
      rabbits). Schirmer's tests, tear film break-up time (BUT) and rose bangle (rb)
      staining were performed on the eyes of two groups at 1, 2, 3, 4 weeks, 2 and 3
      months. The Chiron Diagnostics ACS: 180 Automato Chemilluminescence Systems was
      used to determine the two groups' testosterone level in serum at pre-castrate and
      post-castrate. Results were analyzed statistically. Lacrimal gland, Harder's
      gland, conjunctiva, cornea and limbus were removed for observation
      histopathologically after three months. RESULTS: Both Schirmer's test and break
      up time scores were significantly lower in the castrated group compared with the
      control group. The difference became more and more prominent in the course of
      observation. Rose bangle staining was positive in the castrated group.
      Testosterone level in serum was significantly lower in the post-castrate than
      that in the pre-cartrate. Histopathological observation showed that lacrimal
      glandular epithelial cells were atrophic and flat, the lumen of gland was
      enlarged and vesicular mucous in acinus cells disappeared. PAS positive material
      and conjunctival globlet cells were significantly decreased in the castrated
      group. Compared with the control group there were no significant morphologic
      changes in the corneal epithelium and limbal stem cells. CONCLUSIONS: The low
      level of testosterone in castrated rabbit may contribute to the atrophy and
      applanation of lacrimal glandular epithelium, disappearance of vesicular mucous
      in acinar cells and the significant decrease of the number of conjunctival
      globlet cells. All these can lead to decrease of both the quantity and quality of
      tear secretion and thus cause the instability of tear film.

PMID- 11840759
TI  - [Keratoprosthesis design and biological response to a synthetic cornea].
AB  - OBJECTIVE: To evaluate the biological response to three different designs of
      synthetic cornea in vivo. METHODS: All devices consist of a transparent center
      and a porous blown periphery. Thirty-five devices were implanted into 35 rabbits'
      corneas and followed up to more than 6 months. Rabbit corneal stromal cells were
      inoculated onto the anterior surface of the synthetic cornea and cultured in
      vitro for one week before the operation. The anterior surface of the optic center
      hydrogel was modified with radio frequency (rf)-argon plasma treatment. RESULTS:
      Fibroplasia occurred 2 weeks after surgery and collagen was detected by 28 days.
      The anterior chamber was normal without detectable leakage of aqueous humor.
      Basic fibroblast growth factor (bFGF) was detected at the interface between the
      device and the tissue by 42 days. CONCLUSIONS: It is demonstrated that rabbit
      limbal epithelial cells can migrate onto the synthetic cornea in vivo.

PMID- 11840761
TI  - [Effects of supplementing calcium, iron and zinc on the fetus development and
      growth during pregnancy].
AB  - OBJECTIVES: The purpose of the present study is to determine the effects of
      supplementing the biscuits fortified with calcium (Ca), iron (Fe) and zinc (Zn)
      for pregnant women from the 5th month of gestation until delivery on the growth
      and development of fetus and to explore the best way to improve infant growth.
      METHODS: A total of 313 healthy and primary pregnant women were enrolled and
      divided into five study groups based on their order visiting the hospitals for
      prenatal care. Each woman of the study groups was given three pieces of biscuit
      fortified with VD, Ca and VD, Ca, Zn and VD (Ca + Zn + VD), Ca, Fe, VC and VD (Ca
      + Fe + VD), Ca, Fe, VC, Zn and VD (Ca + Fe + Zn + VD), respectively, from the 5th
      month of gestation until delivery (24 weeks in total) daily. The fortified levels
      were 10 micrograms Ca from carbonate calcium, 10 mg Zn from lactate zinc, 10 mg
      Fe from ferrous lactate, and 50 mg VC, respectively. A parturient women was
      selected from the same hospital as control after one trial subject for each study
      groups selected. Placenta was weighed and umbilical cord venous blood and
      placenta tissue samples were collected after delivery for measuring Ca and other
      trace elements. Body weight and height of the new-born babies were measured.
      RESULTS: The weight of placenta in control group (551.1 +/- 64.2) g was
      significantly (P < 0.05) heavier than other trial groups with Ca + Fe + Zn + VD
      (467.1 +/- 36.6) g, but contents of Ca and other trace elements in placenta of
      the control group were lower, which probably because of the lower nutrients
      intake of mothers in control group that would result in a compensation
      enlargement of placenta to get enough nutrients for fetus from mother. The Hb
      level in cord venous blood was significantly higher than that of maternal blood.
      There was no significant difference in activity of alkaline phosphatase between
      cord venous blood and material blood. The contents of Ca, Fe and Zn in cord
      venous plasma were all significantly higher than those in maternal plasma. Birth
      weight and height in Ca + Fe + Zn + VD group were the highest in all the groups,
      with birth weight of (3.53 +/- 0.33) kg, as compared with (3.28 +/- 0.54) kg in
      the control group. There was significant correlation between birth weight, weight
      for age and intake of Ca, Fe and Zn during pregnancy. CONCLUSION: Supplementation
      of Ca + Fe + Zn + VitD during pregnancy is the best way to improve infant
      development and growth, based on the current Recommended Dietary Allowances (RDA)
      for pregnant women.

PMID- 11840760
TI  - [Effects of supplementing of calcium, iron and zinc on women's health during
      pregnancy].
AB  - OBJECTIVES: To determine the effects of supplementing biscuits fortified with
      calcium (Ca) and vitamin D (VD), iron (Fe), vitamin C (VC) and zinc (Zn) to
      pregnant women from the 5th month of gestation until delivery on their health,
      and to explore a way to improve their Ca, Fe and Zn nutritional status during
      pregnancy. METHODS: A total of 313 healthy and primary pregnant women were
      enrolled and divided into five study groups based on their order visiting the
      hospitals for prenatal care. Each woman of the study groups was given three
      pieces of biscuit fortified with VD, Ca and VD, Ca, Zn and VD (Ca + Zn + VD), Ca,
      Fe, VC and VD (Ca + Fe + VD), Ca, Fe, VC, Zn and VD (Ca + Fe + Zn + VD),
      respectively, from the 15th month of gestation until delivery (24 weeks in total)
      daily. The fortified levels were 10 micrograms VD, 400 mg Ca from carbonate
      calcium, 10 mg Zn from lactate zinc, 10 mg Fe from ferrous lactate, and 50 mg VC,
      respectively. A parturient women was selected from the same hospital as control
      after one trial subject for each study groups selected. RESULTS: The daily
      dietary intakes of Ca, Zn and Fe in pregnant women were only 47.7%, 54.7% and
      86.7% of the Recommended Dietary Allowances for Chinese. Incidence of anemia for
      mid-term pregnant women was 35.2%, and Fe-supplementation could significantly
      improved their hemoglobin level (P < 0.05). Prevalence of anemia in the groups of
      Ca + Fe + Zn + VD and Ca + Fe + VD was 35.3% and 40.7%, respectively, before Fe
      supplementation and reduced to zero and 4.0%, respectively, after Fe
      supplementation. Whereas, prevalence of anemia in the other groups without Fe
      supplementation still kept in a relatively high level. In the groups supplemented
      with Ca, their plasma Ca level increased, especially with the best results in Ca
      + VD group. Plasma level of Zn declined with length of gestation, which could be
      improved by Zn supplementation. Serum level of alkaline phosphatase activity
      increased a little bit with length of gestation. There was no significant
      difference in radial and ulnar bone mineral density (BMD) between trial groups
      and controls two months after delivery. Maternal radial and ulnar BMD correlated
      significantly with their dietary Ca intakes in Ca + VD group. CONCLUSION: The
      best way to improve maternal nutritional status is supplementation of Ca + Fe +
      Zn + VitD, based on the Recommended Dietary Allowances for Chinese.

PMID- 11840762
TI  - [Effects of vitamin A and iron supplementation on the improvement of iron status
      and immunological function in preschool children].
AB  - OBJECTIVE: In order to understand the changes in immunological function in rural
      preschool children with lower levels of vitamin A and iron, and the effect of
      vitamin A and iron supplementation on the improvement of iron status and
      immunological function. METHODS: Serum vitamin A concentration and hemoglobin
      (Hb), serum iron (SI), transferrin saturation (TS), serum ferritin (SF) were
      determined in 270 rural preschool children aged 3-7 years in Beijing, and the
      subjects were divided into four groups based on their determinations: control,
      lower serum vitamin A, lower iron, and both lower iron and serum vitamin A. Forty
      subjects were selected from each group, and serum IgA, IgG, IgM and interleukin-2
      (IL-2) were determined for them. Forty-one subjects who had lower iron and lower
      serum vitamin A (< 1.12 mumol/L) were divided into two groups: one of them
      supplemented with 30 mg iron element (ferrous sulfate 0.15 g) once a day for 8
      weeks, and the other group supplemented with iron and 12,500 IU vitamin A twice a
      week for 8 weeks. After supplementation of vitamin A and iron, their serum
      vitamin A, hematological iron index and serum immunological index were determined
      again for the two groups. RESULTS: Serum IgM were (1,260 +/- 310) mg/L in both
      lower iron and serum vitamin A groups, significantly higher than that in normal
      group (1,070 +/- 170) mg/L (P < 0.05). But there were no significant differences
      in serum levels of IgG, IgA and IL-2. After supplementation of iron and vitamin
      A, their serum TS increased to (26.5 +/- 8.6)%, significantly higher than that
      before supplementation and that supplemented with iron only (22.3 +/- 3.8)%. And,
      their serum IL-2 were (278.9 +/- 117.7) ng/L after supplementation, significantly
      higher than that before supplementation (161.6 +/- 90.3) ng/L and that in those
      supplemented with iron only (189.5 +/- 89.3) ng/L. There was no significant
      difference in other biochemical indices of iron and immunological indices.
      CONCLUSIONS: Supplementation with vitamin A and iron was helpful to improve body
      iron nutritional status and immunological function obviously in preschool
      children with iron-deficiency and sub-clinical deficiency of vitamin A.

PMID- 11840763
TI  - [Correlation between nutrient levels of vitamin A and zinc and HOX C4 gene
      expression in mice embryos].
AB  - OBJECTIVE: Correlation between nutrient levels of vitamin A and zinc and HOX C4
      (3.5) gene expression in mice embryos was studied. METHODS: The Kunming female
      mice were divided three groups: deficient group (DG) fed with fodder deficient of
      vitamin A and zinc, replenished group (RG) fed with fodder deficient of vitamin A
      and zinc until the 7th day after conception and then fed with fodder rich in
      vitamin A and zinc, and normal group (NG), fed with normal fodder. After obvious
      symptoms of vitamin A and zinc deficiency appeared, the mice were mated. On the
      12th day after conception, pregnant mice were killed and their levels of vitamin
      A and zinc were determined and the content of mRNA of HOX C4 (3.5) were
      determined for the embryos with situ hybridization. RESULTS: The level of vitamin
      A was 0.44 mumol/L, 1.03 mumol/L and 1.40 mumol/L, respectively and that of zinc
      124.3 mg/kg, 152.1 mg/kg and 193.8 mg/kg in DG, RG and NG, respectively. The mRNA
      of HOX C4 (3.5) gene expression in mouse embryos increased significantly in DG,
      RG and NG (P < 0.05). CONCLUSIONS: Levels of vitamin A and zinc in the body of
      pregnant mice positively correlated significantly with their HOX C4 (3.5) gene
      expression, with coefficients of correlation of 0.78 to 0.99.

PMID- 11840764
TI  - [A study on the resources coping with occupational stress in teachers].
AB  - OBJECTIVE: To explore the status of the resources coping with occupational stress
      in teachers. METHODS: Occupational stress inventory revised edition (OSI-R) was
      used to measure their occupational stress, strain and psychological coping
      resources for 1,460 teachers in primary and secondary schools and 319 non-teacher
      intellectuals. Analyses were focused on coping resources of teachers. RESULTS:
      The higher the level of coping resource of teachers, the lower the personal
      strain in them, with an inverse correlationship. Coping resource in the teacher
      group was significantly higher than that in the non-teacher group, with scores of
      (130.4 +/- 18.2) and (126.9 +/- 19.1), respectively. Coping resource in teachers
      decreased with the increase of age, with the scores from (134.1 +/- 18.1) in the
      group aged less than 30 to (128.5 +/- 17.5) in the group aged 50. Coping resource
      in the female teachers was significantly higher than that in the male teachers,
      with scores of (131.4 +/- 18.3) and (129.4 +/- 18.1), respectively. Coping
      resource in the primary school teachers was significantly higher than that in the
      secondary school teachers, with scores of (132.7 +/- 18.1) and (128.5 +/- 18.1),
      respectively. CONCLUSION: It is important to enhance teacher's coping resource,
      especially for the male teachers in the secondary schools, for improving their
      teaching efficiency.

PMID- 11840765
TI  - [Evaluation of protective efficacy of two tuberculosis DNA vaccines by lung
      histopathological analysis].
AB  - OBJECTIVE: To evaluate the protective efficacy of MPT64 and ESAT6 DNA vaccines
      from M. tuberculosis. METHODS: BALB/c mice were randomly divided into five groups
      and subjected to the following treatments respectively, i.e. immunized with
      saline (A), plasmid vector (B), M. bovis BCG (C), MPT64 DNA vaccine (D) or ESAT6
      DNA vaccine (E); and then infected by intraperitoneal injection with M.
      tuberculosis H37Rv. The lung histopathological changes were observed 5 or 10
      weeks after infection by microscopy. RESULTS: At 5 weeks after infection, the
      lung lesions in the mice of group A and B had inflammatory infiltration with
      epithelial cell granulomas. In the mice of group C, main pathological changes
      were epithelial cell granulomas with moderate granulate hyperplasia in alveolar
      walls. The lung lesions of 3 mice in group D and 1 mice in group E were similar
      to those seen in the mice in group A and B. The lung lesions of 2 mice in group D
      and 4 mice in group E were similar to those seen in the mice in group C. At 10
      weeks after infection, their tuberculous pneumonia tended to recovery. For the
      mice in groups A, B and D, their lung pathology exhibited tuberculous granulomas
      consisted of numerous macrophages, lymphocytes and a few epithelial cells with
      moderate granulate hyperplasia in alveolar walls. For the mice in groups of C and
      E, their lung developed epithelial cell and lymphocytic granulomas with moderate
      to severe granulate hyperplasia in alveolar walls. Lung tissue necrosis was not
      observed in any mouse. CONCLUSIONS: MPT64 and ESAT6 DNA vaccines from M.
      tuberculosis could enhance immunity against M. tuberculosis. The protective
      efficacy of ESAT6 DNA vaccine is stronger than that of MPT64 DNA vaccine, but not
      stronger than that of Mycobacterium bovis BCG.

PMID- 11840766
TI  - [A field evaluation of the epidemiological efficacy of an attenuated live
      hepatitis A vaccine (H2 strain)].
AB  - OBJECTIVE: To evaluate the epidemiological efficacy of an attenuated live
      hepatitis A vaccine (H2 strain). METHODS: A randomized and controlled field trial
      was carried out in part of Zhengding County and the Jiaoqu District of
      Shijiazhuang city. There were about 37,000 children in these areas involved in
      the study and they were randomly divided into a vaccine group and a control group
      according to the months they were born. Children in the vaccine group were given
      a dose of 10(6.5) TCID50/ml attenuated live hepatitis A vaccine while those in
      the control group were given nothing. As soon as the children in the vaccine
      group had been vaccinated, all the subjects were carefully followed up for
      hepatitis A cases. RESULTS: In the 3.5 years of follow-up, there were 20
      hepatitis A cases in the control group and the incidence rate was 136.4 per
      100,000 population. There was only one hepatitis A case in the vaccine group and
      the incidence rate was 8.1 per 100,000 population. The difference of the
      incidence rates between the two groups was highly significant (P < 0.001) and the
      protective efficacy of the vaccine was 94.4% (95% CI: 67.1%-100%). CONCLUSION:
      The protective efficacy of the vaccine was excellent and the vaccine is suitable
      to be widely used.

PMID- 11840767
TI  - [Intrauterine growth retardation and cerebral palsy].
AB  - OBJECTIVE: To obtain the prevalence of cerebral palsy in children affected with
      intrauterine growth retardation (IUGR) and to explore the association between
      IUGR and cerebral palsy. METHODS: A cross-sectional survey was carried out among
      children aged under 7 years in seven cities of south Jiangsu Province. RESULTS:
      There were 5.6% (95% CI 5.6% to 5.7%) of the children classified as IUGR with a
      bimodal distribution, the highest in the 35-36 and 42-43 weeks of gestational
      age. The prevalence of cerebral palsy (CP) in IUGR children was 5.7@1000 (95% CI
      of 4.7@1000 to 6.9@1000), 4.2 times more than that in non-IUGR children (95% CI
      of 3.4-5.2). The prevalence of CP in IUGR children of preterm and term delivery
      (< 37 weeks and > or = 37 weeks of gestational age) was 1.9 (95% CI of 1.2 to
      3.0) and 4.2 (95% CI of 3.3 to 5.3) times more than that in non-IUGR children,
      respectively. Multiple logistic regression analysis showed the effect of IUGR on
      CP for children with birth weight greater than 2,500 g, after controlling for
      birth weight and gestational age. CP prevalence in IUGR children was two times
      more than that in non-IUGR children. Furthermore, prevalence of IUGR in children
      with birth weight lower than the 3rd percentile and in those with the 3rd
      percentile to lower than the 10th percentile was 3.4 and 1.8 times more than that
      in non-IUGR children, respectively. CONCLUSIONS: The prevalence of cerebral palsy
      in IUGR children was 5.7@1000, 4.2 times that in non-IUGR children and IUGR is an
      independent risk factor for cerebral palsy.

PMID- 11840768
TI  - [The associations between concentration of selenium in semen and sperm parameters
      as well as oxidative DNA damage in human sperm].
AB  - OBJECTIVE: To explore the associations between concentrations of selenium (Se) in
      serum and semen and sperm parameters as well as oxidative DNA damage in human
      sperm. METHODS: Concentrations of selenium in serum and semen were determined
      using atomic absorption spectrophotometer (AAS). The sperm parameters were
      detected according to WHO laboratory manual for the examination of human sperm.
      The levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and deoxyguanosine (dG) in
      human sperm DNA were measured using HPLC-ECD and HPLC-UV. RESULTS: Mean semen
      concentration of selenium was significantly higher in fertile subjects (0.74
      mumol/L) than that in infertile subjects (0.56 mumol/L), while there was no
      significant difference in serum concentrations of selenium between the two
      groups. Semen volume (3.91 ml vs. 2.79 ml), sperm density (46.4 x 10(9)/L vs.
      36.5 x 10(9)/L) and sperm count (168.0 x 10(6) vs. 102.0 x 10(6)) were
      significantly higher in fertile subjects than those in infertile subjects. There
      was no significant difference in motility and viability of sperm, and proportion
      of deformity sperm between the two groups, Significantly positive correlation was
      observed between semen concentration of Se and sperm density (r = 0.48, P < 0.01
      for fertile subjects and r = 0.32, P < 0.05 for infertile subjects) as well as
      sperm count (r = 0.32, P < 0.05 for fertile subjects and r = 0.26, P < 0.05 for
      infertile subjects), sperm motility (r = 0.46, P < 0.01 for fertile subjects and
      r = 0.65, P < 0.01 for infertile subjects) and viability (r = 0.33, P < 0.05 for
      fertile subjects and r = 0.64, P < 0.01 for infertile subjects). There was no
      correlation between serum Se concentrations and sperm parameters. Moreover, 8
      OHdG levels in sperm DNA inversely correlated with semen Se concentrations in
      fertile (r = -0.21, P < 0.05) and infertile (r = -0.28, P < 0.05) subjects.
      However, no significant correlation was found between 8-OHdG levels in sperm DNA
      and serum Se concentrations in all subjects. CONCLUSIONS: Semen concentrations of
      Se were associated with sperm quality and 8-OHdG levels in human sperm. Serum
      concentrations of Se did not affect sperm quality and oxidative DNA damage in
      human sperm.

PMID- 11840770
TI  - [Experimental study on carcinogenic activity of the organic extracts from water
      of the sifangtai section of songhua river].
AB  - OBJECTIVES: To study the carcinogenic activity and potential mechanism of the
      organic extracts from the Songhua River in vitro. METHODS: The in vitro cell
      transformation and single cell gel electrophoresis (SCGE) tests were detected
      with the ether extracts of water. The expression of anticancer genes p53, p16,
      and p21 measured by immunohistochemical assays and the apoptosis by TUNEL assay
      were also studied. RESULTS: The extracts from the water induced malignant
      transformation of BALB/C mouse embryo fibroblast cells and induce DNA damage.
      p53, p16 and p21 failed to express in transformed cells induced by the water
      extracts, and the apoptosis rate of transformed cells decreased. CONCLUSION: This
      study demonstrates that the organic extracts from the Songhua River has potential
      carcinogenicity.

PMID- 11840769
TI  - [Effects of aluminum on amino acid neurotransmitters in hippocampus of rats].
AB  - OBJECTIVES: To study the effects of long-term exposure to aluminum on amino acid
      transmitters in hippocampus of rats. METHODS: Sprague-Dawley rats were randomly
      divided into four groups based on their body weight. Aluminum chloride was added
      into diet at doses of 0, 11.2, 55.9 and 111.9 mg/kg BW for 90 days successively.
      Neurobehavioral testing consisted of open field and passive-avoidance
      conditioning. The contents of amino acids were detected by HPLC. Aluminum was
      measured by atomic absorption spectroscopy. RESULTS: The spontaneous motor
      ability in the open field and the latency of passive avoidance in aluminum
      treated rats were decreased as compared with the controls. In hippocampus, the
      contents of aspartate (Asp) and glutamine (Gln) were significantly increased at
      the dose of 111.9 mg Al3+/kg BW (P < 0.05, P < 0.01), while taurine (Tau) was
      significantly increased at doses of 55.9 and 111.9 mg Al3+/kg BW(P < 0.05) as
      compared with control. The increased values of aluminum were significantly
      related to the dosage of aluminum. CONCLUSION: The altered content of amino acid
      neurotransmitters in hippocampus might be one of the important mechanisms of
      aluminum neurotoxicity.

PMID- 11840771
TI  - [Studies on the effects of tea catechins against hepatitis B virus infection].
AB  - OBJECTIVE: To examine the effects of tea catechins against hepatitis B virus and
      their roles in protecting liver damage. METHODS: A duck hepatitis B virus
      infection model was established by using one-day-old Beijing ducklings. The
      infected ducklings were divided into six groups: three treatment groups of
      different dosages (60, 120 and 240 mg/kg of tea catechins p.o., 93.7% total
      catechins and 48.7% EGCG), positive control group (Are-AMP, i.v.), model group
      (water, p.o.) and negative control group (no DHBV, no catechins). Serum DHBV-DNA
      was tested by dot blot hybridization (marked with digogenin), DHBsAg was assayed
      by ELISA. The morphologic changes of liver and the activities of ALT and AST were
      also measured. RESULTS: Levels of DHBsAg and DHBV-DNA in duck serum were
      significantly decreased in all the three catechin treated groups (P < 0.05, P <
      0.01). Activities of ALT and AST were also significantly decreased after
      treatment for 25 days and 14 days after the end of the treatment (P < 0.05, P <
      0.01). Results of liver pathological examinations also provided positive
      evidence. CONCLUSIONS: The protective effects of tea catechins against hepatitis
      B virus infection were significant. It protected the liver functions and reduced
      the pathological changes of the liver tissue.

PMID- 11840772
TI  - [Meta-analysis on the association of ACE/ID polymorphism and essential
      hypertension in Chinese population].
AB  - OBJECTIVE: To study on the association of the insertion(I)/deletion(D)
      polymorphism of the angiotensin-converting enzyme gene intron 16 (ACE/ID) and
      essential hypertension(EH) in Chinese population by the means of meta-analysis.
      METHODS: Odds ratios of ACE/ID genotype distributions in EH patients against
      healthy control were analysed. All the relevant studies were identified, poor
      qualified studies were eliminated, and the risk of publication bias was excluded.
      The meta-analysis software, REVMAN3.1, was applied for investigating
      heterogeneity among individual studies and summarising effects across studies.
      RESULTS: A total of 1,612 cases and 1,710 controls from 18 studies were included.
      No heterogeneity among the studies has been found. The frequencies of the ACE DD,
      ID and II genotypes were 23%, 41%, and 36% in cases and 19%, 46% and 35% in
      controls respectively. The pooled odds ratio (with 95% CI) of DD vs ID + II is
      1.37(1.15-1.63) (P < 0.01), while the pooled odds ratio of II vs ID + DD is 0.96
      (0.83-1.12) (P > 0.05). CONCLUSION: In Chinese population (mainly the Hans), DD
      genotype is associated with the increased risk of EH.

PMID- 11840773
TI  - [Effects of polymorphism of apolipoprotein E gene on body mass index and plasma
      lipid levels in obese children].
AB  - OBJECTIVE: To investigate the association between body mass index (BMI) and
      plasma lipid levels in obese children with different apolipoprotein E (ApoE)
      genotypes. METHODS: BMI, ApoE genotype and plasma level of lipid were measured in
      324 obese children. Genotype of ApoE was performed with polymerase chain reaction
      (PCR). RESULTS: Distribution of genotypes was E3/3 in 198(61.1%), E3/4 in
      36(11.1%), E2/3 in 54 (16.7%) and E4/4 in 36(11.1%). In the ApoE3 group, BMI
      correlated significantly with all indices of blood lipid (P < 0.05). However,
      with the exception of low-density lipoprotein-cholesterol (LDL-C), triglyceride
      (TG), apolipoprotein B (ApoB), correlation between other indices of blood lipid
      and BMI varied in the ApoE genotypes. In the ApoE2 group, BMI correlated
      significantly with TG (P < 0.05), but not with ApoA I or high-density lipoprotein
      cholesterol (HDL-C). In the ApoE4 group, BMI correlated significant with HDL-C
      and ApoA I (P < 0.05), but not with TG. CONCLUSION: Polymorphism of the ApoE gene
      could play a role in association of BMI with plasma level of lipid.

PMID- 11840774
TI  - [Oocyst structure and problem of coccidian taxonomy].
AB  - A comparative ultrastructural study was made of both thin- and thick-walled
      oocysts of Cryptosporidium parvum. According to the authors' findings, all the
      oocysts in C. parvum should be considered as thin-walled, since their walls have
      been composed of a single membrane or of two, closely apposed membranes without
      any additional substance in between. Despite the presence of two types of wall
      forming bodies (WFB) in the maturing macrogamete or zygote, there is no evidence
      of their involvement in oocyst wall formation. In this concern, the function and
      destiny of WFB in C. parvum oocysts still remain obscure. Similar structure of
      the oocysts wall was reported elsewhere for thin-walled oocysts of fish coccidia
      of the genera Goussia and Eimeria. In C. parvum, the "thick-walled" oocysts
      differ from oocysts with thin walls in the availability in the former of a single
      sporocyst. The sporocyst wall consists of two unequal layers: a thin outer layer
      and a thicker inner one, in which a characteristic suture line is occasionally
      seen. By this feature the thick-walled oocysts of C. parvum bear similarities
      with oocysts of the cyst-forming coccidia (Cystoisospora, Toxoplasma,
      Sarcocystis) and of the genus Goussia: in all these the valves making up the
      sporocyst wall are joint just along the suture line. The literary and the
      authors' own data make it possible to suppose that the suture detected in C.
      parvum oocysts is located in the sporocyst wall, joining its valves, rather than
      in the oocyst wall proper, known to be composed of one or two, closely apposed
      unit membranes. Again, the availability of a suture (or sutures) in the sporocyst
      hardly provides enough reason to relate C. parvum with either cyst-forming, or
      fish coccidia, since this structure itself may be of a convergency character,
      rather than of systematic value. This may be substantiated, at least in part, by
      the authors' previous findings (Beyer, Sidorenko, 1984) of a similar structure,
      originally referred to as a "slit channel", in the intraerythrocytic capsule
      around gamont stage of haemogregarines--the adeleid coccidia of the genus
      Karyolysus. The suture-like structure could have originated in the evolution
      independently in different groups of parasitic protozoa to serve eventually as a
      suitable mechanism for immediate separation of elements involved in protective
      formation harbouring different developmental stages, including, for example,
      sporozoites in the eimeriid coccidia, or gamonts in the adeleid coccidia.

PMID- 11840775
TI  - [Ultrastructure of melanocytes from retina and choroid of the Pacific salmon].
AB  - The ultrastructure of the retina and choroid cells in three species of the
      Pacific salmon, Oncohrynchus gorbuscha, O. keta and O. masou, was studied. The
      structure of retina pigment cells is similar in all the three species, only a
      small difference was found in the percentage of lengthened and rounded forms of
      melanosomes. Melanocytes of the masu salmon differ also in the structure of their
      nuclei. The pigment cells of choroid differ from those of retina by a more
      extended form of melanosomes and by the presence of less rounded melanosomes. In
      the chum salmon retina we found electron lucent "contact vesicles", whose
      assignment is open to discussion. In retina pigment cells of the masu salmon
      smolts ready for migration, the activity of Golgi appararus rises, mitochondria
      and mature melanosomes increase in number. The choroid pigment cells are slightly
      swollen, their processes more often and deeper penetrate into the walls of
      vessels, down to the endothelium. Results of the experiment with the application
      of an artificial magnetic field (AMF) have shown that the retina and choroid
      pigment cells in the masu salmon fry react to the field of a certain direction.
      The phenomenon of magnetosensitivity of pigment cells is discussed in addition to
      their possible involvement in magnetoreception.

PMID- 11840776
TI  - [Effect of clinorotation on the intensity of lipid peroxidation and superoxide
      dismutase activity in pea chloroplasts].
AB  - The lipid peroxidation intensity and the antioxidant enzyme superoxide dismutase
      (SOD) activity were studied in chloroplasts of Pisum sativum under clinorotation
      (for 7 and 14 days) for elucidating mechanisms of biological effect of altered
      gravity. In comparison with the control, increased LP levels in chloroplasts were
      established during both the terms of clinorotation. The SOD activity rose in the
      chloroplasts of plants clinorotated for 7 days, which has a significant
      protective effect. However, under a longer clinorotation (for 14 days) the SOD
      activity fell, being, however, higher than in the control samples. In accordance
      with the Selye oxidative stress theory, plants clinorotated for 7 days are in the
      phase of growing stability, while plants clinorotated for 14 days are in the
      phase of decreasing stability.

PMID- 11840777
TI  - [Rat embryo fibroblasts transformed by complementation with oncogenes E1A+E1B-19
      and E1A+cHa-ras differ in the ability to realize the G1/S block in serum free
      media].
AB  - The capability of REF cells transformed by EA + E1B-19 kDa and EA + cHa-ras
      oncogenes to realize the G1/S cell cycle arrest upon serum starvation was
      studied. The amount of cyclin-kinase inhibitor protein p27/Kip was shown to
      increase in both normal and transformed cells. However, the p27/Kip-bound cyclin
      kinase complexes of transformed cells were found to be active, implying the
      functional inactivation of p27/Kip inhibitor. Nevertheless, in contrast to E1A +
      cHa-ras transformants, E1A + E1B-19 kDa transformants undergo the G1 cell cycle
      arrest. The G1 cell cycle block correlates with the decrease in cyclinE-Cdk2
      activity. Since cyclinE-Cdk2 complexes need Thr-160 phosphorylation of Cdk2 by
      CAK-kinase for full activity, we have analysed the Cdk-7 associated activity upon
      serum starvation using gst-Cdk2 as a substrate. Serum starvation did not affect
      CAK activity either in E1A + cHa-ras or in E1A + E1B-19 kDa transformants. Thus,
      selective suppression of cyclineE-Cdk2 activity in E1A + E1B-19 kDa transformants
      upon serum starvation does not arise from the action of cyclin-kinase inhibitors,
      or from change in CAK activity.

PMID- 11840778
TI  - [The role of SRC kinase in activation of transcription factor STAT1].
AB  - Transcription factor STAT1 (Signal Transducers and Activators of Transcription)
      takes part in signal transduction from receptors of growth factors and many
      cytokines, including interferons. In this paper, the role of tyrosinkinases Src
      and JAK2 was estimated in activation of STAT1 by epidermal growth factor (EGF)
      and hyperosmotic shock. Using a pharmacological inhibitor of Src kinases CGP77675
      and cells with knockout c-src, it was shown that Src activated STAT1 upon
      stimulation by both epidermal growth factor and hypersomatic shock. In contrast,
      JAK2 activity exerted no influence on these processes.

PMID- 11840779
TI  - [Identification of elements responsible for regulation of keratinocyte growth
      factor gene by steroid hormones and 1,25-dihydroxyvitamin D3].
AB  - Data are provided on the up-regulation of keratinocyte growth factor gene (kgf)
      at mRNA and protein level in prostate cancer cells (LNCaP) stimulated by 1,25
      dihydroxy-vitamin D3 and 17-beta-estradiol (E2). The computer analysis of the 5
      flanking region of kgf gene using different software and databases (TESS,
      TRANSFAC etc.) enabled us to identify some potential elements responsible for
      binding the nuclear receptors of vitamin D3, E2, and some other steroid hormones.

PMID- 11840780
TI  - [The inhibition enzymatic hydrolysis of acetylthiocholine by acetylcholinesterase
      using principal alkaloids isolated from celandine and macleya and their
      derivatives].
AB  - A study was made of a possible inhibitory action on the enzymatic hydrolysis of
      acetylthiocholine by human erythrocyte acetylcholinesterase of principal
      alkaloids isolated from Chelidonium majus L. and Macleaya (Bocconia) cordata and
      microcarpa (namely sanguinarine, chelidonine, berberine), and of drugs "Ukrain"
      (thiophosphoric acid derivative of a sum of the alkaloids isolated from
      Chelidonium majus L.) and "Sanguirythrine" (a mixture of unseparated closely
      related to benzo[c]phenanthridine alkaloids sanguinarine and chelerythrine,
      isolated from Chelidonium majus L. and other plants of Papaveraceae family). All
      agents under study have been shown to be reversible inhibitors of the enzymatic
      hydrolysis of acetylthiocholine. On the basis of the kinetic data it has been
      determined that chelidonine belonged to reversible inhibitors of a competitive
      type. All other examined agents have been demonstrated to be inhibitors of a
      mixed competitive-noncompetitive type, and a greater contribution to the
      inhibition was made by the competitive constituent. Among all examined agents
      berberine, sanguinarine and "Sanguirythrine" were the strongest inhibitors of
      this reaction (the values of generalized inhibitory constants being 0.23, 0.23
      and 0.29 microM, respectively) and cheliodonine and "Ukrain" were much weaker
      (2.0 and 2.5 microM, respectively). Judging from the data obtained, sanguinarine
      and chelerythrine exert similar inhibitory effects on the reaction of enzymatic
      hydrolysis of acetylthiocholine, since sanguinarine and "Sanguirythrine" have
      nearly equal generalized inhibitory constants.

PMID- 11840781
TI  - [Effect of arachidonic and other fatty acids on the intracellular calcium
      concentration and calcium signaling in peritoneal macrophages].
AB  - Effects of arachidonic and other fatty acids on the intracellular Ca2+
      concentration ([Ca2+]i) in rat peritoneal macrophages was investigated. It has
      been shown that cis-polyunsaturated arachidonic and linoleic induce a significant
      and dose-dependent increase in [Ca2+]i, which is due to depletion of thapsigargin
      sensitive Ca2+ store and to stimulation of Ca2+ entry from the extracellular
      medium. Pharmacological characteristics of Ca2+ entry induced by arachidonic acid
      appeared to be similar to those of store-dependent Ca2+ entry activated by
      thapsigargin or cyclopiazonic acid; Ca2+ entry is attenuated by the same Ca2+
      channel inhibitors, by tyrosine kinase inhibitor genistein and epoxygenase
      inhibitor proadifen. Cis-monounsaturated oleic and saturated myristic acids
      appeared to be less effective and induced only a slight increase in [Ca2+]i at
      much higher concentrations. Arachidonic and other fatty acids can also stimulate
      Ca(2+)-ATPase in the macrophage plasma membrane. The data are compatible with the
      important role played by arachidonic and other free fatty acids in the regulation
      of [Ca2+]i in peritoneal macrophages.

PMID- 11840782
TI  - [The effect of medium viscosity on actin polymerization].
AB  - A comparative study of the influence of two factors--excluded volume effect, and
      medium viscosity--on actin polymerization was carried out. Dextrane--500 (1%),
      poly(ethylene)glycol--6000 (2.7%), Ficol (1.8%), methyl cellulose (0.04%),
      saccharose (10%), and glycerine (10%) were used for creating a viscous medium.
      The concentrations of these agents in actin solution made approximately the same
      viscosity commensurable with the cytoplasm viscosity. By this it was possible to
      bring conditions of actin polymerization in vitro closer to those in vivo. It is
      shown that the medium viscosity in contrast to the excluded volume effect,
      prolongs the nucleation phase during actin polymerization. A conclusion is made
      that in the cell both factors can be involved in the regulation of actin filament
      formation.

PMID- 11840783
TI  - [ Effect of gamma radiation, cis-diamminedichloroplatinum and its derivates on
      the Escherichia coli cell survival and potentiality for adaptive response].
AB  - The sensitivity to the lethal effect of gamma-rays, cis- and trans
      diamminedichloroplatinum (DDP), cis- and trans-iminoethers of DDP (IE) was
      compared in two groups of E. coli--K12 and B. In all experiments, cells of wild
      types appeared to be most resistant to these agents. gamma-Resistant and gamma
      sensitivity/hypersensitive strains occupy an intermediate position according to
      their sensitivity to cis-DDP derivatives. In almost all the cases, both single
      and especially double mutants defective for the systems of nucleotide excision
      repair, recombination repair, and inducible SOS-repair are most sensitive to DDP
      derivatives. The data obtained show that in E. coli the repair of lethal lesions
      after cis-DDP action is more complicated than after gamma-irradiation. Of DDP
      derivatives cis-DDP is most effective, while trans-DDP is less effective, and cis
      and trans-IE are considerably less effective, respectively. It is shown that the
      effects of ionizing radiation in low doses (more than 10 different regimes), or
      of treatment with cis-DDP in low concentrations do not change the survival of E.
      coli after their respective effects in high doses. In other words, under the
      effect of ionizing radiation and cis-DDP no adaptive response for the lethal
      action was found in E. coli.

PMID- 11840784
TI  - [Karyotype polymorphism in species of Daiswa hainanensis subsp. vietnamensis
      Takht].
AB  - Karyotypes of two plants Daiswa hainanensis (Merrill) Takht. subsp. vietnamensis
      from Northern Vietnam were investigated. On using nucleotid-specific
      fluorochromes, heterochromatin blocks rich in AT- and GC-nucleotid pairs were
      revealed. Parameters and idiograms of these karyotypes are given. In the
      karyotype of one plant, a somatic abbreviation (a clearly marked morphological
      heteromorphism of homologues) was found. The karyotype of the other plant
      contains a supernumerary chromosome of euchromatin nature. Cytogenetic features
      of the genus Daiswa corroborate the correctness of A. L. Takhtajan's suggestion
      that Daiswa is a separate genus. The population polymorphism as a base for
      speciation in the process of phylogenesis is discussed.

PMID- 11840785
TI  - [Chromosome-like bodies of dysentery ameba Entamoeba histolytica].
AB  - Intact and surface stretched amembraneous nuclei of Entamoeba histolytica
      (Rhizopoda, Lobosea, Entamoebidae) trophozoites were studied by light and
      electron microscopy. A moderately dense karyosome about 1.5 microns in diameter,
      localized in the central part of the interphase nucleus, contains the bulk of
      nuclear DNA. Within the karyosome, beaded and ribbon-like chromatin bodies
      surrounding a loose fibrillar core are commonly recognized. The peripheral domain
      of both interphase and several mitotic nuclei is filled with a heterogeneous
      material similar in its ultrastructure to the nucleolar substance. A wide
      fibrogranular domain lies between this unusual nucleolus and the karyosome.
      Rosette-like intranuclear inclusions 0.2-0.4 micron in diameter are often seen in
      both the fibrogranular and nucleolar domains. At the prophase-metaphase, nearly
      50 linear chromosome-like bodies are detected as being in close association with
      several large beaded and ribbon-like chromatin bodies. At the anaphase-telophase,
      the chromatin bodies per surface-stretched daughter nucleus of live entamoebae,
      and in each amembraneous daughter nuclear preparation number nearly 14 and 6,
      respectively. Besides, in each amembraneous DAPI-stained nucleus a set of 50 or
      so linear chromosome-like bodies are clearly identified. We infer that the
      nucleus of E. histolytica contains more than 50 linear chromosomes which at
      different stages of the cell cycle can unite into several beaded and ribbon-like
      associations. These form a single moderately dense chromatin karyosome in the
      central part of the interphase nucleus.

PMID- 11840786
TI  - [In memory of Sir Alan Hodgkin (1914-1998)].

PMID- 11840787
TI  - [On the sidelines? Comments on asthenopia].

PMID- 11840788
TI  - [Cyclotropia in macula translocation. Possible eye muscle surgery solutions].
AB  - BACKGROUND: Macular translocation for treatment of age-related maculopathy often
      necessitates surgical counter-rotation of the external eye muscles.
      Excyclorotatory effects can be attained generally by various surgical methods on
      all extraocular eye muscles. If procedures on different muscles are combined,
      anterior segment perfusion has to be maintained. PATIENTS AND METHODS: The
      results of 29 operations were analysed in order to examine the excyclorotatory
      effects of 4 different combined surgical approaches. RESULTS: In 23 patients a
      partial transposition of all 4 m. recti together with a high dose combined
      operation on both oblique muscles yielded a mean effect of 21.6 degrees
      excyclorotation. In four patients a vertical transposition of the horizontal m.
      recti in opposite directions together with a high dose combined operation on both
      oblique muscles led to a mean excyclorotation of 22 degrees. A full tendon
      transposition of the superior oblique muscle to the nasal part of the orbit in
      one case combined with a downward transposition of the medial rectus muscle
      resulted in an excyclorotation of 37 degrees, in another case combined with an
      anterior margin advancement of the inferior oblique muscle led to an
      excyclorotation of 35 degrees. CONCLUSIONS: All approaches yielded mean counter
      rotatory effects over 20 degrees. The indications are discussed under the aspects
      of the possibility of a one-step correction of horizontal or vertical angles,
      dosage, induction of inconcomitancies and operation time.

PMID- 11840790
TI  - [Does the type of lens influence stereoscopic vision].
AB  - PURPOSE: Age and monofocal intraocular lens (IOL) are assumed to reduce the
      quality of stereopsis, whereas multifocal intraocular lenses (MIOL) are supposed
      to provide better random dot stereopsis than monofocal IOL. The following study
      investigates whether and how the different IOL types (including the different
      existing principles of MIOL) influence stereopsis. PATIENTS AND METHODS: We
      included 153 persons from six groups (young and elder phakic subjects, patients
      with bilateral monofocal IOL, with bilateral diffractive MIOL, with bilateral
      refractive MIOL, and with unilateral diffractive/refractive MIOL). Stereopsis
      measurements were performed using the Pola test with a two-dimensional and a
      random dot test for far and near distances and the results for near distance were
      compared with the Lang random dot, two-dimensional Titmus, and the Monje real
      three-dimensional tests. Near and distance monocular and binocular visual acuity
      and orthoptic examinations had been previously carried out. RESULTS: Of the young
      phakic subjects, 81-92% correctly perceived the Pola test figures, and 100% did
      so in the Lang, Titmus, and Monje tests. Of the elder phakic subjects, 36-73%
      correctly perceived the Pola test, and 52-88% did so in the Lang, Titmus, and
      Monje tests. Of the patients with bilateral monofocal IOL, 19-62% perceived the
      Pola test figures, as did 30-61% of the patients with bilateral diffractive MIOL,
      12-53% of the patients with bilateral refractive MIOL, and 5-29% of the patients
      with unilateral diffractive/refractive MIOL. CONCLUSION: All patients with
      bilateral mono- or different multifocal IOL had good binocular vision in far and
      near distance including random dot stereopsis.

PMID- 11840789
TI  - [Differential regulation of expression of PDGF receptors on corneal epithelial
      cells].
AB  - BACKGROUND: The function of platelet-derived growth factor (PDGF) during corneal
      wound healing is only incompletely understood to date. Previous studies have
      shown that the mRNA of PDGF receptor type alpha (PDGFR alpha) and type beta
      (PDGFR beta) is expressed in cultured corneal epithelial cells (CEP). To add to
      the current knowledge, the following study was designed to compare the expression
      of mRNA and protein of both PDGF receptor subtypes in cultured CEPs and in CEPs
      ex vivo. METHODS: Total RNA and protein were extracted from cultured CEPs and
      from CEPs ex vivo according to standard protocols. The reverse-transcription
      polymerase chain reaction (RT-PCR) was applied to detect specific expression of
      the mRNA of PDGFR alpha and PDGFRss. The expression of the corresponding proteins
      was detected using Western blotting. RESULTS: MRNA and protein of both PDGF
      receptor subtypes could be detected in cultured CEPs but not in CEPs ex vivo.
      CONCLUSION: The present study shows for the first time that mRNA and protein of
      both PDGF receptor subtypes are expressed in cultured human corneal epithelial
      cells, while corneal epithelial cells ex vivo do not express these receptors. The
      differential up-regulation of PDGF receptors in activated cells during wound
      healing could be of pathophysiological importance.

PMID- 11840791
TI  - [20-MHz ultrasound of pre-saccular lacrimal ducts].
AB  - BACKGROUND: In clinical practice, ultrasound examination of the lacrimal drainage
      system is not able to represent the lacrimal canaliculi with a high quality but
      the high-resolution ultrasound with 20 MHz transducer is a better possibility to
      get images of the lacrimal canaliculi. PATIENTS AND METHODS: A total of 20
      patients suffering from diseases of the lacrimal drainage system were examined
      ultrasonographically. Detection and localisation of the lacrimal canaliculi was
      made by a 20 MHz sector scanner in combination with the ultrasound diagnostic
      system I. After patient positioning, the high-resolution ultrasound investigation
      was done via immersion connection (methylcellulose). Instillation of viscoelastic
      substances (e.g. Healon) was necessary to detect the lacrimal canaliculi.
      RESULTS: In all investigated patients, the high-resolution ultrasound (transducer
      frequency of 20 MHz) allowed reproducible images of the lacrimal drainage system.
      Without viscoelastic substances, a good echographic visualisation of canaliculi
      structures was obtained from patients with chronic canaliculitis or dislocated
      punctum plugs. In chronic canaliculitis the ultrasonic images showed an ectatic
      canaliculus (diverticulum) and high-reflective structures (concrements).
      CONCLUSION: The high-resolution ultrasound (transducer frequency of 20 MHz) seems
      to be well suited for investigations of the lacrimal drainage system. In
      comparison with ultrasound biomicroscopy the resolution is lower but the depth of
      penetration is higher. The use of 20 MHz ultrasonic examination can be helpful in
      the clinical diagnostic of chronic canaliculitis.

PMID- 11840792
TI  - [Intracameral anesthesia with lidocaine in cornea guttata].
AB  - BACKGROUND: Combined topical and intracameral anesthesia has become increasingly
      popular in cataract surgery. We analyzed the use of intracameral anesthesia in
      patients with corneal dystrophy who had undergone cataract surgery. PATIENTS AND
      METHODS: We measured the number of endothelial cells in 40 eyes with Fuchs'
      corneal endothelial dystrophy preoperatively as well as three times
      postoperatively (after 1 day, 4 weeks, and 3 months). Performing sponge
      anesthesia, the additional application of 0.15 ml lidocaine 1% was randomized.
      RESULTS: The lidocaine group showed the following loss of endothelial cells in
      the central cornea: 1 day postoperatively 9.2%, 4 weeks later 9.7%, and 3 months
      after surgery 10.7%. The other group had a postoperative loss of endothelial
      cells in the central cornea of 8.8% (1 day), 9.3% (4 weeks), and 10.5% (3
      months). No significant differences between the two groups were observed.
      CONCLUSIONS: Cornea guttata is not a contraindication for the use of intraocular
      lidocaine.

PMID- 11840793
TI  - [Prism correction in heterophoria].
AB  - Unlike heterotropia (= manifest strabismus), heterophoria (= latent strabismus)
      is not a primarily existing condition but is a reaction to an interruption of the
      sensory-motor feedback control system. The reaction consists of a deviation from
      the orthovergence position. Binocular vision causes a continuous calibration of
      the vergence position. This "orthophorisation" explains that in most persons,
      heterophoria differs only slightly from zero. Nevertheless, a small heterophoria
      is common (70-80% of the population). The need to compensate for heterophoria by
      sensory-motor fusion can cause asthenopic complaints, such as headaches with
      prolonged reading. Since a variety of other defects can lead to similar symptoms,
      a causal relationship with heterophoria can be assumed only after a thorough
      differential diagnosis. Prism spectacles or eye muscle surgery for heterophoria
      should be recommended only after prism trials in free space, which include yoked
      prisms as a placebo control. Heterophoria should be distinguished from
      "Winkelfehlsichtigkeit", which is a deviation from orthoposition that results
      from the "measuring and correcting methodology after H.-J. Haase" (MKH) and is
      based on the idea that fixation disparity, a minute deviation from orthovergence
      position, indicates an inability to overcome a larger "vergence angle at rest".
      Objective recordings have, however, revealed that the subjective tests with
      stereo cues applied in the MKH can mislead to the assumption of a fixation
      disparity although both eyes are aligned exactly to the fixation point. A trial
      conducted in the Netherlands concerning the therapy of asthenopic complaints
      showed no statistically significant advantage of prism spectacles determined with
      the MKH over conventional spectacles.

PMID- 11840794
TI  - [Childhood vision disorders. Screening programs in international comparison].
AB  - Worldwide in a number of countries, screening programs aimed at detecting visual
      disorders in children are established. Repeatedly, proposals are brought forward
      to optimize already existing programs. Countries without such a program are
      interested in learning about current models as a guide for planning their own
      program. This study was performed to take stock of the screening programs for
      visual dysfunction in children in existence in the years 1999-2000 worldwide. The
      aspects considered were the child's age at examination, examiner's qualification,
      type of examinations performed, cost-bearing entity, and cost-efficacy analysis.
      The health ministries of 190 sovereign countries were asked via a questionnaire
      for information about possibly existing screening programs. The results of the
      survey were analyzed quantitatively regarding geographic, political, and
      socioeconomic aspects, yielding data for the exchange of experience in optimizing
      existing programs and developing new programs.

PMID- 11840795
TI  - [Immune suppression by combination therapy with basiliximab and cyclosporin in
      high risk keratoplasty. A pilot study].
AB  - BACKGROUND: The risk of postoperative immune reaction/transplant rejection is
      increased in the presence of distinct risk factors. In these situations, the use
      of established immunosuppressive agents (steroids, cyclosporin) is indicated.
      However, immune reactions can occur despite this therapy. Basiliximab is a
      monoclonal antibody with a high specific binding affinity to the IL-2 receptor of
      activated T-cells. After renal transplantation, the combination therapy with
      basiliximab and cyclosporin reduces the risk of acute rejection by 30% against
      placebo. The aim of this study was to investigate the effect of complementary
      immune suppression with the IL-2 synthesis inhibitor cyclosporin and the IL-2
      receptor antagonist basiliximab on the incidence of transplant rejection after
      high-risk keratoplasty. PATIENTS AND METHODS: In an open pilot study, seven
      patients with high-risk keratoplasty were treated with basiliximab
      perioperatively and cyclosporin postoperatively. All patients had penetrating
      keratoplasty with a non-HLA-matched corneal graft. RESULTS: Seven patients were
      operated on from 12/98 through 12/99 with a corneal transplant diameter between
      7.1 and 9.5 mm. Risk factors included extensive corneal neovascularization in all
      patients (indications for surgery: 4 cases with corneal scars after herpetic
      disease, 2 cases with conditions after alkali burns, 1 case with corneal
      ulceration after thermal burn). During the follow-up of 14-25 months, no immune
      reaction has occurred, and all transplants are clear. The mean visual acuity
      increased from 0.04 to 0.41 postoperatively. DISCUSSION: The preliminary data on
      a combination therapy with basiliximab and cyclosporin are promising. For further
      evaluation a prospective multicenter study is planned.

PMID- 11840796
TI  - [Intracorneal silicone oil deposits].
AB  - BACKGROUND: A patient with intraocular silicone oildeposits underwent paracentral
      corneal incision but the corneal sutures were never removed and 7 years later a
      perforating corneal transplantation was performed due to corneal opacification.
      METHODS: The corneal button was fixed in 10% buffered paraformaldehyde, embedded
      in celloidin and sections 200 microns thick were cut and stained with van Gieson.
      Some of these sections were embedded in paraffin and 5 microns thick sections
      were cut. RESULTS: Celloidin sections showed intrastromal silicone oil droplets
      located adjacent to defects in Descemets' membrane and corneal sutures but the
      endothelial cells contained no silicone oil droplets. CONCLUSION: Silicone oil
      can penetrate the corneal stroma in cases of defects in Descemets' membrane.

PMID- 11840797
TI  - [Mono- or bilateral abducens paralysis as the initial symptom of sinus vein
      thrombosis].
AB  - BACKGROUND: Sinus vein thrombosis is a rare intracerebral complication of
      mastoiditis. We report on the clinical ophthalmologic symptomatology of this
      secondary illness. PATIENTS AND METHODS:  HISTORY: two young female patients,
      aged 14 and 3.5 years, presented at our pediatric ophthalmology section due to
      diplopia. Both girls had suffered 1-2 weeks earlier from otitis media, which had
      been treated with antibiotics. Other neurological symptoms were not reported.
      CLINICAL COURSE: Best corrected visual acuity was 20/20 OD/OS in both patients.
      Ocular alignment revealed a bilateral abduction deficit in the 14-year-old girl
      and a monolateral abduction deficit of the right eye in the younger patient.
      Ophthalmoscopic examination evidenced bilateral papilledema in both patients.
      Magnetic resonance tomography and magnetic resonance angiography showed
      mastoiditis and thrombosis of the sigmoid and transverse sinuses. THERAPY:
      Following mastoidectomy, high-dose antibiotic therapy, and full-dose heparin
      therapy, rapid improvement occurred. CONCLUSIONS: Thrombosis of the sigmoid sinus
      following mastoiditis is a rare but severe complication of middle ear
      inflammation. Immediate surgical and antibiotic therapy is necessary. Symptoms
      can possibly occur even when the primary focus seems to resolve.

PMID- 11840798
TI  - [Diagnosis and therapy of LASIK-induced neurotrophic epitheliopathy].
AB  - Laser in situ keratomileusis (LASIK) has emerged as the standard surgical
      procedure for the correction of refractive errors and in the last years a lot of
      experience has been gained. Consequently, the amount of intraoperative, early and
      late postoperative complications have significantly decreased. Keratitis punctata
      superficialis and dry eye symptoms are the most frequent postoperative
      complications. A decreased corneal sensitivity attributable to the cutting of the
      corneal sensory nerves has been described after LASIK. In addition pathological
      tear secretion tests and typical dry eye symptoms have been reported. Until know
      it has not been completely evaluated, if these symptoms are a combination of the
      dry eye disease and LASIK-induced symptoms or if they are due to an independent
      LASIK complication, the so-called LASIK-induced neurotrophic epitheliopathy.
      Independently of the incompletely understood etiology, much care and a sufficient
      therapy with artificial tears should be applied to such patients. To increase the
      comfort of LASIK, adequate intra- and postoperative treatment is necessary to
      enhance the patient satisfaction.

PMID- 11840799
TI  - [Subacute, unilateral vision loss. Schwannoma of the orbital apex].

PMID- 11840800
TI  - [Ocular complications of diode laser epilation in the area of the face. Loss of
      pupillary symmetry and pigment layer defect as well as coagulation of the ciliary
      body with intraocular inflammation caused by laser treatment].

PMID- 11840801
TI  - [Good clinical practice. Significance for clinical research].

PMID- 11840802
TI  - [Clinical and hemodynamic effects of anaprilin and carvedilol in patients with
      coronary heart disease].
AB  - 50 patients with postinfarction cardiosclerosis and angina pectoris (functional
      class I-IV) having left ventricular ejection fraction < 45% entered a comparative
      cross-over trial of antianginal effectiveness of anaprilin and carvediolol
      (dilatrend). In 10 patients carvedilol was compared to placebo. Carvedilol is
      shown to demonstrate higher antianginal activity which is the highest in patients
      with angina pectoris of low load. The analysis of peripheral vascular resistance
      and double product attributes antianginal advantages of carvedilol to its more
      potent effect on cardiac performance due to peripheral vasodilatation.

PMID- 11840803
TI  - [ECG based diagnosis of right ventricular hypertrophy in patients with chronic
      obstructive bronchitis].
AB  - Two mathematical models developed on the basis of a discriminant analysis of the
      evidence obtained in examination of 84 patients with chronic obstructive
      bronchitis (COB) are proposed in early diagnosis of right ventricular hypertrophy
      (RVH) by ECG readings in COB patients. Application of hierarchic classification
      model is recommended for diagnosis of RVH in screening. The probability model is
      intended for follow-up of COB patients.

PMID- 11840804
TI  - [Apolipoprotein genes in patients with ischemic heart disease].
AB  - The role of allele variants of apoB, apoCIII, and apoE genes in genetical
      predisposition to coronary disease was studied in Kazakhs and Uigurs. A total of
      241 coronary patients and 205 healthy controls (all males) were examined. ApoB,
      apoCIII, and apoE gene polymorphism was studied by the polymerase chain reaction
      with thermostable Tag DNA polymerase. No significant relationship between the
      studied genes polymorphism and coronary disease was detected in the Kazakhs and
      Uigurs.

PMID- 11840805
TI  - [Analysis of tuberculosis mortality in a general hospital of a large city].
AB  - In thanatogenesis of tuberculosis in emergency cases admitted to general
      hospitals in 1998-2000 predominated acute destructive prigressive forms which are
      most unfavourable epidemiologically. At autopsies tuberculosis is encountered 3
      times more frequently. The diagnosis of tuberculosis is missed because of
      critical condition of the patients and their short stay in hospital due to early
      lethal outcome which doesn't allow adequate examination for tuberculosis.

PMID- 11840806
TI  - [The role of hepatitis C virus RNA detection in various substrates of patients
      with chronic hepatitis C].
AB  - Puncture biopsy of the liver and blood count were made in 72 patients with
      chronic hepatitis C (CHC). Morphological alterations in the liver were assessed
      by Knodell index. The blood serum, lymphocytes and hepatic tissue were examined
      for a genome form of hepatitis C virus (HCV) RNA, blood lymphocytes and hepatic
      tissue--for a relevant replication form. HCV RNA was detected using "nested" RT
      PCR. Only 26% patients had symptoms of asthenovegetative and dyspeptic syndromes.
      Normal alaninaminotransferase (ALT) level was observed in 24% patients, the rest
      had it high. HCV RNA was encounted more frequently in hepatic tissue than
      lymphocytes or serum (83, 68 and 46%, respectively). A replication form of HCV
      RNA was present in hepatic tissue of 31% patients and was absent in the
      lymphocytes. The incidence of the RNA detection was not related either to the
      disease symptoms or morphological alterations in hepatic tissue. The occurrence
      of the genome and replication forms in hepatic tissue does not correlate to ALT
      level. HCV RNA occurs more often in the serum, blood lymphocytes and in three
      substrates simultaneously in patients with hyperalatemia.

PMID- 11840807
TI  - [Prediction and diagnosis of drug intolerance in patients with purulent infection
      and burn disease].
AB  - The immunological study was made in which the drug sensitivity index according to
      S. M. Demyanenko was estimated in 76 patients (24 women and 52 men aged 17-73
      years): in patients with soft tissue purulent infection (group 1, n = 46) and
      surface thermal burns (degree III-IV) of 40% body surface (group 2, n = 30).
      Patients with satisfactory drug tolerance served control (16 patients of group 1
      and 10 ones of group 2). Correlations between humoral and cellular immunity
      parameters and drug sensitivity index were studied. The results may serve a basis
      for development of early and adequate correction of immunological disorders in
      the above patients, of drug-related complications caused by immunological
      imbalance.

PMID- 11840808
TI  - [Chrono-pharmacodynamics of capoten in patients with ischemic heart disease,
      postinfarction cardiosclerosis with cardiac failure].
AB  - Hemodynamic parameters were measured before and 30 min, 1, 2 and 3 hours after
      intake of 12.5 mg capoten in acute pharmacological test at 7.00, 10.00, 13.00,
      16.00, 19.00 and 22.00 in 70 patients with ischemic heart disease, postinfarction
      cardiosclerosis with heart failure stage I-II. The patients were randomized into
      6 groups according to the time of the pharmacological test. As shown by
      tetrapolar chest rheography, the lowest peripheral vascular resistance and the
      highest cardiac ejection occurred if capoten was used at 10.00. In contrast,
      vascular resistance rose and cardiac ejection fell in capoten intake at 13.00. At
      the other hours circulation responded more favourably than at 13.00 but not so
      strongly as at 10.00. Different hemodynamic reaction to capoten within 24 hours
      demands further studies.

PMID- 11840809
TI  - [Tavanik effectiveness and safety in the treatment of urinary tract infection
      complications].
AB  - 20 patients with complicated urinary infection (CUI) have been treated with
      levofloxacine (tavanik) for 10 days in a single daily dose 250 mg. They were
      compared with 23 acute pyelonephritis patients given ciprofloxacin in a dose 1
      g/day. None of the patients had purulent inflammation or was treated with
      antibacterial drugs. The response to tavanik and its safety were good or very
      good in 95% patients. With ciprofloxacin the same results were achieved in 88%
      patients. 3 patients failed this treatment. 2 patients developed purulent
      pyelonephritis and were operated. The number and intensity of side effects were
      higher were less in the tavanik group. Thus, tavanik, a new antibacterial drug
      from fluoroquinolone group, is effective and low-toxic in complicated infection
      of the urinary tracts.

PMID- 11840810
TI  - [Galstena therapy of some hepatobiliary diseases].
AB  - Galstena was given to 10 patients with chronic cholecystitis, 15 patients with
      chronic hepatitis and 15 patients with fatty degeneration of the liver for 30
      days in a dose 10 drops 3 times a day 30 min before meal. The effect of the drug
      was assessed in relation to biliary inflammation and motility, inflammation and
      metabolism in a hepatic cell. It was found that galstena improves motor function
      of the biliary tract and exocrine function of the liver, reduces activity of
      mesenchymo-inflammatory syndrome and fatty degeneration of the liver.

PMID- 11840811
TI  - [Electric methods of catheter ablation of cardiac arrhythmia].

PMID- 11840812
TI  - [Diagnosis of angina pectoris].

PMID- 11840814
TI  - [Arrhythmias and cardiac conduction disorders: psychosomatic and
      psychotherapeutic aspects].

PMID- 11840813
TI  - [Desaggregation therapy of acute glomerulonephritis].

PMID- 11840815
TI  - [Differential diagnosis of joint hypermotility syndrome].

PMID- 11840816
TI  - [Recurrent thrombosis of deep veins of the lower limbs in a patient with
      hyperhomocysteinemia].

PMID- 11840817
TI  - [A case of infectious endocarditis with affection of the three valves in a
      patient on chronic hemodialysis].

PMID- 11840818
TI  - [Two cases of Gaucher's disease in adults].

PMID- 11840819
TI  - [Adaptation and health. A letter to the editor about R. M. Baevskii's article
      "Problems of Health and Standard Parameters: the Position of a Physiologist"].

PMID- 11840820
TI  - [Clinico-biological significance of hepatitis B virus mutations].

PMID- 11840821
TI  - [Evaluation of colorimetric method for analysis of glycated hemoglobin].
AB  - The level of glycated hemoglobin (GH) measured by the Diabetic test colorimetric
      method did not depend on the compensation. On the other hand, its level was
      increased in diabetes mellitus decompensation in comparison with subcompensation,
      if isoelectrofocussing of the studies hemolysates was carried out prior to
      colorimetry. Study of colorimetric migration of hemolysates showed that they were
      represented by a background which could distort the results.

PMID- 11840822
TI  - [Blood carboxyhemoglobin in anemia of pregnancy].
AB  - Carboxyhemoglobin was measured over the course of normal gestation (in the first,
      second, and third trimesters) and in patients with anemia of the first, second,
      and third degree of severity. Carboxyhemoglobin level increased 2-fold by the end
      of gestation. Its level depended on the severity of anemia, the highest
      concentration (2.8 times increased) being detected in the patients with third
      degree anemia.

PMID- 11840823
TI  - [Microsatellites instability--actuality and clinical significance in hyperplastic
      processes and endometrium neoplasm (review of literature)].

PMID- 11840824
TI  - [The role of erythrocyte rheological determinants in the regulation of bloodflow
      structure].
AB  - Correlations of rheological determinants of the erythrocyte viscous
      characteristics were studied in normal subjects and coronary patients treated
      traditionally and with photohemotherapy. A rigid relationship between erythrocyte
      deformability and aggregation was detected in the patients. Blood exposure to He
      Ne laser and UV is a potent method for correcting the blood rheology.
      Physiological significance of the rigid relationship of erythrocyte deformability
      and aggregation consists in the maintenance of the structure of flowing blood,
      characteristic of its native status, and represents an additional mechanism of
      realization of the adaptive potential of blood viscosity regulation in mammals.

PMID- 11840825
TI  - [Modern technologies in clinical microbiology and chemotherapy. Automated working
      place of a medical microbiologist, chemotherapist and epidemiologist (Lecture)].

PMID- 11840827
TI  - [Effect of sex on rheological properties of blood in adults].
AB  - The purpose of this study was to evaluate blood rheology in adult subjects aged
      17-95 years. A total of 1035 volunteers (515 men and 520 women) took part in the
      study. The criterion of participation in the study was age over 17 years and that
      precluding the participation was hospital treatment. Blood, plasma, and serum
      viscosity and erythrocyte aggregation and deformability were analyzed on a
      rotation viscosimeter. Blood rheological properties depended on sex. Whole blood
      viscosity and plasticity were notably higher in men than in women at all ages.
      Whole blood viscosity in women aged 20-29, 40-49, and over 60 years is lower than
      in men of the same age, despite changed protein/water ratio in the plasma and
      serum.

PMID- 11840826
TI  - [The content of double bonds in blood serum lipids from patients with myocardial
      infarction].
AB  - Hypocholesterolemia and hypotriglyceridemia during the first days of myocardial
      infarction (MI) is a result of enhanced absorption of saturated fatty acids in
      the form of triglycerides within very low density lipoproteins (VLDL) through
      apoE/B-100 receptors. This is followed by inhibition of this endocytosis,
      accumulation of saturated fatty acids VLDL in the blood, and
      hypertriglyceridemia. Permanent level of double bonds in MI (ozone titration)
      results not from MI but from blocking of cell absorption of polyenic fatty acids
      in the form of cholesterol polyesters in low-density lipoproteins (LDL) through
      apoB-100 receptors, which is characteristic of atherosclerosis. High molar ratio
      of double bonds/cholesterol in comparison with the double bonds/glycerol ratio
      indicates that the majority of polyenic fatty acids in the blood lipoproteins
      present as cholesterol polyesters. Lipoprotein transfer and cell absorption of
      saturated fatty acids alone are selectively impaired in MI. Selective impairment
      of cell absorption of saturated or polyenic fatty acids alone or a combination of
      both is observed in some diseases. Ozone titration of serum lipid double bonds
      reflects impaired absorption of essential polyenic fatty acids by cells.

PMID- 11840828
TI  - [Membrane and immunological aspects of perinatal nervous system disorders in
      newborns].
AB  - Results of clinical, biochemical, and immunological studies in 157 full-term
      newborns with perinatal hypoxic damage to the nervous system are analyzed.
      Activation of lipid peroxidation processes in platelet membranes (increased
      levels of dienic conjugates and Schiff bases), activation of endogenous
      phospholipases and lysosomal enzymes (cathepsin D and acid phosphatase) were
      revealed. Free-radical and enzymatic aggression led to stabilization of the lipid
      bilayer, which manifested by increase of enzymatic lysoforms and decrease in the
      total phospholipid content of membranes. Study of lymphocyte subpopulations by
      means of monoclonal antibodies and measurements of immunoglobulin concentrations
      showed that perinatal hypoxia impaired the formation of immune status. Acute
      hypoxia promoted the formation of transitory "stress immunodeficiency", while
      chronic hypoxia induced more stubborn immune disorders.

PMID- 11840829
TI  - [Cytokine regulation of liver inflammation and fibrosis during chronic hepatic
      diseases].
AB  - Serum concentrations of antiinflammatory cytokines and growth factors were
      measured in 30 patients with chronic viral hepatitis (HCV), mainly HCV RNA, and
      10 patients with liver cirrhosis (LC), classes B and C according to Child-Pew.
      Serum concentrations of tumor necrosis factor-alpha (TNF alpha), granulocytic
      macrophagal colony-stimulating factor (GM-CSF), and growth-transforming factor-1
      beta (TGF1 beta) were increased in 63.86 and 80% patients with HCV and LC,
      respectively, and differed significantly (p < 0.05) from the control. The level
      of TNF alpha positively correlated with the concentration of alanine
      aminotransferase (r = 0.14). A positive correlation between TGF1 beta and
      histologic activity index was detected (r = 0.16). Increased levels (p < 0.05) of
      IL-5, TNF alpha, and TGF1 beta were detected in LC patients in comparison with
      the control. Patients with LC concomitant with anemia had higher (though not
      significantly) concentrations of TNF alpha in comparison with patients without
      anemia. Increased levels of proinflammatory cytokines and growth factors in the
      sera of patients with HCV and LC indicate activation of immunocompetent cells,
      including mononuclear phagocytes. These data are in line with experimental
      findings, indicating an important role of the studied cytokines in the
      development of hepatic inflammation, fibrosis, and cytopenic syndromes.

PMID- 11840831
TI  - [The quality of laboratory diagnosis of viral hepatitis and analysis of factors
      affecting the reliability of results].

PMID- 11840830
TI  - [ An out-break of opisthorchiasis in 1999 in Cheliabinsk as a result of eating
      the imported fish. Use of modern method of laboratory diagnosis].

PMID- 11840832
TI  - [Rationalization of cooperation of physicians and a clinical laboratory as
      exemplified by Medical Center of the Russia Central Bank].

PMID- 11840833
TI  - [Evaluation of informative value of laboratory tests and test complexes for the
      occupational diseases].
AB  - The authors discuss the criteria for rational selection of laboratory parameters
      most informative for the diagnosis of occupational diseases. Such criteria as
      diagnostic significance, diagnostic specificity, diagnostic informative value
      according to Kulback (Igx), and diagnostic selectiveness ensure the optimal
      selection of laboratory parameters for the diagnosis of occupational diseases.
      Diagnostic sensitivity is not a stable value, as it depends on the disease
      severity and degree of exposure to harmful factors. Basic requirements, which
      should be taken account of when selecting the complex of laboratory methods for
      the diagnosis of occupational diseases, are defined.

PMID- 11840834
TI  - [Methodological aspects of the use of furanacryloyl-phenylalanyl-glycyl-glycine
      for the photometric detection of angiotensin converting enzyme activity].
AB  - Photometric evaluation of serum activity of angiotensin-converting enzyme (ACE)
      making use of synthetic chromogenic substrate N-(3-[2-furyl]acryloyl)-phe-gly-gly
      (FAPGG) is analyzed. Spectral characteristics of FAPGG are investigated. The
      Burger-Lambert-Bar dependence is not observed in any of the working
      concentrations. Extension of the spectral weight band is associated with the
      appearance of the absorbency/concentration linear function for FAPGG solution.
      Under such conditions the registered intensity of the analyzer sign (delta
      OD/min) is in strong correlation with the spectral weight band. As a result, high
      inter-analyzer variations were observed. This impedes the standardization of the
      method and prompts the use of attested calibrators. Linear function of analyzer's
      sign and ACE level is theoretically achieved at FAPGG concentration 1.0 +/- 0.2
      mM (Km = 0.35 +/- 0.05 mM, minimum saturation concentration 1.4 +/- 0.2 mM).
      Synthetic ACE inhibitors are recommended to rule out the interference.

PMID- 11840835
TI  - Risk of inadequate intakes of vitamins A, B1, B6, C, E, folate, iron and calcium
      in the Spanish population aged 4 to 18.
AB  - A meta-analysis of the most representative Spanish nutrition studies was carried
      out to identify inadequate intakes of vitamins, A, B1, B6, C, E, folate, iron,
      and calcium in children aged 4 to 18. Information on vegetable, fruit and fruit
      juice/beverage intake was also solicited. Data drawn from the selected studies
      yielded a total of 6540 children and adolescents in eight geographical areas. The
      sample was stratified by age (children: 4 to 14 years old and adolescents: 13-18
      years old) and sex. Inadequate intakes (below two-thirds of the recommended
      values) were notable in children for vitamin E, vitamin C, and vitamin A and in
      girls, iron. In adolescents, low intakes were especially marked for vitamin E and
      vitamin A, and in girls, calcium, folate, and iron. Adolescents consumed more
      vegetables, fruit juice, and fruit drinks whereas children had higher fruit
      intakes. Regional differences in consumption were also detected. Strategies for
      improving nutrient intake in these vulnerable populations are discussed.

PMID- 11840836
TI  - Plasma protein oxidation and antioxidant defense during aging.
AB  - BACKGROUND: Oxidative stress is an important process that occurs in vivo during
      aging and is considered one of the main causes of molecular damage to cellular
      and tissue structures. These changes can accumulate in biological structures
      during aging. OBJECTIVE: The aim of this work is to evaluate plasma protein
      oxidative damage, measured as carbonyl groups content, and the concentration of
      some antioxidant molecules (vitamins and carotenoids) in 122 healthy volunteers
      (50 males and 72 females), 25 to 89 years old. RESULTS: Total plasma proteins
      slightly decreased with age, but the level of carbonyl groups was similar in the
      adult (< 65 years) and in the old, and was similar in both sexes. Plasma
      concentration of antioxidant molecules such as alpha-tocopherol, beta-carotene
      and other carotenoids, increased with age and correlated with the level of
      lipoproteins; plasma total cholesterol and triglycerides were significantly
      correlated with age as well. CONCLUSIONS: The surprisingly normal level of plasma
      protein carbonyl groups in our older subjects suggests two possibilities: a) the
      older people in our study are healthy and free from pathologies because of better
      protection against oxidative injury during their lifetimes, i.e., they maintained
      low-level oxidative damage on plasma proteins; or b) the level of carbonyl groups
      is normal because of the high turnover in plasma: the oxidized circulating
      proteins are preferentially and quickly removed; in this case oxidative damage is
      not discernible in plasma proteins but may proceed silently in other tissues.

PMID- 11840837
TI  - Effect of dietary cholesterol and fat levels on lipid peroxidation and the
      activities of antioxidant enzymes in rats.
AB  - The aim of this study was to investigate the effect of dietary fat levels, with
      or without cholesterol, on lipid peroxidation and the activities of antioxidant
      enzymes in rats. Thirty-two Wistar rats aged 4 weeks were divided into 4 groups
      and fed high (20%; HF) or low (5%; LF) fat, with or without 1% cholesterol, for 6
      weeks. Cholesterol feeding resulted in significantly higher concentrations of
      serum cholesterol, but lowered serum triacylglycerol levels. Cholesterol feeding
      also led to markedly decreased levels of hepatic thiobarbituric acid reactive
      substances (TBARS) and lower activities of hepatic superoxide dismutase (SOD),
      glutathione peroxidase (GSH-Px), catalase, and glucose-6-phosphate dehydrogenase
      (G6PDH) when compared with cholesterol-free counterparts in both HF and LF diets.
      On the other hand, rats fed high-fat diets showed increased serum and liver
      TBARS, but decreased hepatic GSH-Px, SOD, and G6PDH activities. Hepatic catalase
      activity was lower in rats fed cholesterol-containing diets, but higher in rats
      fed high-fat diets, and interaction existed between cholesterol and fat feeding.
      These results suggested that dietary cholesterol might delay lipid peroxidation
      and decrease the activities of the hepatic antioxidant enzymes. The degree of
      lipid peroxidation was also influenced by dietary fat levels.

PMID- 11840838
TI  - Lycopene supplementation attenuates the inflammatory status of colitis in a rat
      model.
AB  - The aim of this study was to examine the influence of lycopene and beta-carotene
      on the inflammatory status in a rat model of induced-colitis. Using the 2,4,6
      trinitrobenzenesulfonic acid (TNBS) model, colitis was induced in thirty-two male
      Wistar rats divided into four groups. Each group received a different diet regime
      in parallel with the induction of colitis and was sacrificed after seven days.
      The groups were divided as follows: Group A: without colitis and fed a normal
      chow diet; Group B: induced with colitis and fed a diet supplemented with
      lycopene (300 micrograms/rat/day); Group C: induced with colitis and fed a diet
      supplemented with beta-carotene (300 micrograms/rat/day); Group D: induced with
      colitis and fed a normal chow diet. Colonic inflammation following TNBS induction
      was characterized by hemorrhagic necrosis and fibrosis of the mucosa, increased
      colonic wall thickness, infiltration of inflammatory cells, and increased
      myeloperoxidase (MPO) activity. Supplementation of lycopene in the diet had a
      beneficial effect on the various macroscopic parameters examined including:
      colonic thickness, colon weight, and total area of inflammation. Furthermore, the
      level of myeloperoxidase (MPO) was significantly lower in the lycopene-treated
      group compared to the control group. In terms of microscopic changes, a more
      attenuated inflammatory reaction was observed in the group fed a diet
      supplemented with lycopene. No significant effect was noted in the beta-carotene
      supplemented group. Therefore, we propose that the dietary supplementation of
      lycopene may be an effective approach for reducing the level of oxidative stress
      and improving the inflammatory status of colitis.

PMID- 11840839
TI  - Dietary adrenergic active compounds and the response of broilers to isoproterenol
      and cyclic adenosine monophosphate in vitro.
AB  - Broiler chickens, growing from 7-28 days of age, were fed diets containing 18%
      protein and 0, 1, 10 or 100 mg/kg yohimbine (alpha 2-adrenergic antagonist) or
      metaproterenol (beta-adrenergic agonist) to determine the role of adrenergic
      agents in the regulation of feeding behavior and metabolism. Data from this
      experiment suggest that beta-adrenergic agonists have slight effects on feed
      intake, growth and more pronounced effects on metabolism in the broiler chicken.
      In vitro lipogenesis (IVL) was determined by incubating liver explants for 2 h at
      37 degrees C in the presence of cAMP or isoproterenol (ISO) and [2-14C]acetate
      and by measuring acetate incorporation into total hepatic lipid. Metaproterenol
      and yohimbine (100 mg/kg) depressed growth from 7 to 28 days. Both metaproterenol
      and yohimbine (100 mg/kg) decreased (P < 0.05) IVL compared to controls. These
      dietary additions also decreased (P < 0.05) hepatic malic enzyme activity without
      affecting the activities of either isocitrate dehydrogenase or aspartate
      aminotransferase.

PMID- 11840841
TI  - A matter of antitrust. Revamp of task force appears to be up in air.

PMID- 11840840
TI  - Significance of fortified beverages in the long-term diet of German children and
      adolescents: 15-year results of the DONALD Study.
AB  - Fortified beverages and instant drinks are the most frequently consumed fortified
      products in children and adolescents in Germany. However, little is known about
      the contribution of these products to micronutrient intake. Between 1986 and
      2000, consumption of fortified food (total and the subgroup of fortified
      beverages) and time trends in energy and micronutrient intake were assessed on
      the basis of 3 day-weighed dietary records (n = 4358) of males and females
      between the ages of 2 and 14 years (n = 398/408) enrolled in the DONALD Study
      (Dortmund Nutritional and Anthropometric Longitudinally Designed Study). As
      percentage of recent references for micronutrient intake, a significant increase
      in intake from fortified beverages was observed for calcium (from 1 to 3%), iron
      (3 to 4%), vitamin A (5 to 15%), and vitamin C (5 to 60%). Significant increases
      in intakes were only observed from 1995-1997 for vitamin E, folate, and niacin
      (all 5 to 15-25%), vitamin B1 and B2 (both 10-15 to 25-30%) and vitamin B6 (20 to
      55%). Thereafter significant decreases were found. Among the fortified beverages,
      juice was the most important for micronutrient intake, followed by soft drinks
      (calcium, vitamin A, E, C, folate, niacin) or by instant beverages (energy, iron,
      vitamin B1, B2, B6). Significant linear and nonlinear time trends in
      micronutrient intakes from fortified food and fortified beverages were observed
      in German children and adolescents.

PMID- 11840842
TI  - A new view of eye-care suit. Utah firm sees optometrists' case as groundless.

PMID- 11840843
TI  - Runaway costs. Healthcare inflation at highest level in 7 years.

PMID- 11840845
TI  - Henry Ford to cut and consolidate.

PMID- 11840844
TI  - Settling down. AHERF to pay $93.7 million to creditors, trusts.

PMID- 11840846
TI  - Which rules-state law or ERISA? Patients' rights case before high court could
      have big impact on HMO enrollees.

PMID- 11840847
TI  - The little hospital that could. Rural Tennessee two-bed facility uses critical
      access program to advantage.

PMID- 11840848
TI  - Happy new year. New York lawmakers approve $1.8 billion to boost healthcare
      industry.

PMID- 11840849
TI  - Up to the challenge. AMA head Maves ready to put controversy aside and take on
      his 'dream job'.

PMID- 11840850
TI  - Debt will keep us together. Mount Sinai NYU Health fights rumors of split.

PMID- 11840852
TI  - Patient steering of another sort. Doctors, fearing bad care, tell those sicker to
      stay clear of capitated plans.

PMID- 11840851
TI  - Life at the top. Philanthropy keeps Sloan-Kettering in the black.

PMID- 11840853
TI  - Costly coverage law. Battling uphill to change Hawaii's healthcare statute.

PMID- 11840855
TI  - Invitation only. HIMSS hopes survey will glean credible results.

PMID- 11840854
TI  - Spend money to make money. Study: medical groups benefit from ample budgets.

PMID- 11840856
TI  - Special report: Washington outlook.

PMID- 11840857
TI  - Web survey. December results: 'looking forward to 2002'.

PMID- 11840858
TI  - 'Wave of the future'. Leapfrog's release of hospital information sets off swell
      of activity.

PMID- 11840859
TI  - Anthrax: the hunt narrows.

PMID- 11840860
TI  - To test or not to test?

PMID- 11840862
TI  - Defining and managing chronic fatigue syndrome.

PMID- 11840861
TI  - Stun guns for everyone.

PMID- 11840864
TI  - [The effect of G-loads on gravity tolerance of monkeys Macaca rhesus during
      antiorthostatic hypokinesia].
AB  - Reported are results of 200 centrifuge runs of 24 monkeys Macaca mulatta.
      Microgravity effects were simulated by 4-wk immobilization with the head tilted
      down at -6 degrees. The investigation was divided into two series. During series
      1, one group of animals was not exposed to centrifugal training, whereas the
      other group was exposed to +Gz at the magnitudes of 1.2, 1.4 and 1.6 G for 30-40
      min 4 to 5 times a week. In series-2, again one group of animals was not trained
      on the centrifuge but the other was trained at +1.2 Gz for 30 min 2 or 3 times a
      week. Functional testing by 30-s runs at +3 Gz was performed before and after
      head-down immobilization. Deterioration of g-load tolerance following simulated
      microgravity in both groups of untrained macaques was ascribed to the
      deconditioning effect of simulated microgravity on the body systems. Centrifugal
      training had, as a rule, positive effect on g-tolerance of the animals though it
      failed to fully eliminate the negative consequences of simulated microgravity.
      This means that search after optimal protocols of application of artificial
      gravity generated by centrifuge needs to be continued. Evaluation of the
      effectiveness of combining centrifugation with other countermeasures against the
      adverse effects of microgravity and development of associated protocols can be
      another area of future research.

PMID- 11840863
TI  - [Evaluation of effectiveness of water-salt supplement in the long-duration "MIR"
      missions].
AB  - Long-term stay of human in microgravity instigates body hypohydration.
      Specifically, it leads to noticeable reduction in the extracellular fluid volume
      and consequent orthostatic instability and some other hemodynamic disorders
      immediately after flight. To prevent these developments and to improve g
      tolerance during descent, the cosmonauts administered a complex of end-of-flight
      countermeasures consisting of, besides the physical and LBNP training sessions,
      water-salt supplements (WSS). Basing on the experience of WSS application in long
      duration space flights we can assert the effectiveness of this method of
      pharmacological body hydration maintenance on the phase of preparation for
      descent and the post-landing period. The present work is an attempt to analyze
      the data about WSS administration and effectiveness on the program of the MIR
      long-term missions.

PMID- 11840865
TI  - [Combined effect of immobilization stress and gamma-irradiation on the blood
      forming system in mice].
AB  - Experiments with mice BALB/C were aimed at studying effects of immobilization
      stress and consecutive total gamma-irradiation at the dose of 2.0 Gy. Disorders
      in the blood system were shown to be a function of phase of the general
      adaptation syndrome (GAS). Acute gamma-irradiation on the stage of GAS resistance
      inhibited adaptive and compensatory potentials of the blood-forming system,
      whereas chronic stress by itself increased the spontaneous rate of chromosomal
      aberrations in nucleus-containing bone marrow cells in experimental animals.

PMID- 11840866
TI  - [Levels of radiation exposure and radiation risk in flights aboard the orbital
      complex "Mir" and the International space station].
AB  - The paper presents results of calculating mean daily values of absorbed and
      equivalent doses from galactic cosmic rays (GCR) and Earth's radiation belts
      (ERB) to crew members on orbital missions aboard Mir and the International space
      station during solar minimum and maximum. Calculated doses were corrected in
      accordance with the dosimetric and spectrometric data from Mir missions 18
      through to 23 that took place in the period of solar minimum. Contribution of
      local and albedo neutrons to equivalent dose was also taken into account.
      Presented are calculated total radiation risk and tumor risk over life time for
      Mir and ISS crews following missions of varying duration, and predictions for
      reduction in life span in view of recent dosimetric data.

PMID- 11840867
TI  - [Immobilized biocatalysts in biotechnological processes].
AB  - In recent years, biotechnology has been stuck with the problem of choosing the
      most technologically convenient way of utilization of biocatalysts using
      bacterial cells or structural formations. Immobilization of bio-objects on solid
      carriers uses the advantages of heterogenic catalysis over homogenous like simple
      separation of byocatalyst from end product on completion of biotechnological
      process, and highly effective transformation or synthesis of organic compounds
      through biomass concentration in fermenter. In addition, immobilized biocatalysts
      exhibit better stability in case of exposure to aggressive temperatures, active
      environmental reactions, and "attack" of foreign microflora. Immobilized
      biocatalyzers can operate repeatedly and owing to the unique specificity show
      promise for wide application in aerospace and environmental medicine.

PMID- 11840868
TI  - [Prediction of individual radio-resistance in animals by the parameters of
      initial endocrine functioning of the organism].
AB  - Predictability of individual radioresistance by initial parameters of endocrine
      functions, i.e. peripheral blood levels of adrenal hormones (corticosterone) and
      thyroid hormones (triiodthyronin and thyroxin) was tested. An integral
      logarithmic index of parameter deviation from the mean statistical norm was used
      as a predictive criterion. The initial corticosterone content was found to be
      very informative of future radioresistance and allowed identification of
      subgroups of animals whose survivability reached 92.3% against group-average
      57.2%. Triiodthyronin also turned to be a predictor as survivability of animals
      positively qualified by the parameter made up 83.5%. In the experiment with
      irradiation of rats with a higher dose resulting in group-average survivability
      of 28.7%, a subgroup with 2.2-fold higher survivability was identified.

PMID- 11840870
TI  - [Morphological and functional study of human endothelium response to hyperthermia
      in vitro].
AB  - Effects of hyperthermia (+42.5 degrees C) on the endothelial monolayer
      organization, actin cytoskeleton and cell viability have been examined in culture
      of human aortic endothelial cells (EC). Short-lasting hyperthermia (1-4 hrs)
      provoked disappearance of stress fibers, redistribution of actin filaments to the
      area of cell-to-cell contacts, shape changes and reorganization of the monolayer.
      It also stimulated formation of intercellular contacts in a preconfluent EC
      culture. The cAMP content was elevated one hour after heat treatment and then
      lowered to negligible values (comparing to the basal cAMP level). Long-lasting
      hyperthermia (6-72 hrs) resulted in EC injury, and damage of endothelial
      monolayer accompanied by increased Chromium-51 release and almost complete
      blockade of [3H]-thymidine incorporation into DNA. Addition of cAMP elevating
      drugs (forskolin, 8-Br-cAMP or isobutylmethylxanthine) into the cell culture
      medium prevented heat-induced decrease in cAMP concentration, stimulated EC
      spreading, protected EC from injury, and promoted integrity of endothelial
      monolayers. Obtained results indicate that long-lasting hyperthermia can be
      regarded as an additional factor of endothelium injury involved in development of
      vascular pathology.

PMID- 11840869
TI  - [Hypoxia as a modality to correct disturbances in bone oxygen uptake at various
      static-kinetic conditions].
AB  - Osteodystrophy models consisted in removing weight loading from hind limbs and
      rats' immobilization; disturbances in bone oxygen uptake were quelled by induced
      gaseous environment with low PO2. Unloading of the hind limbs for 28 days was
      found to decrease oxygen uptake by fragments of the iliac bone, and oxygen
      pressure in m. gastrocnemius. These parameters were unchanged in atmosphere with
      12% of oxygen. Motor restraint of rats in hypoxic atmosphere leads to less marked
      reductions in oxygen demand in iliac fragments and oxygen pressure in m.
      gastrocnemius as compared with breathing ambient air.

PMID- 11840871
TI  - [Influence of geomagnetic activity on the cardiorespiratory system in healthy
      humans].
AB  - Changes in a number of respiration and circulation parameters during magnetic
      storms of varying intensity were analyzed in 126 normal humans belonging to two
      age groups: 19-21 yr. old young men and women (29 of each) and 51-53 yr. old men
      (n = 36) and women (n = 32). Geomagnetic components D, H and Z were used.
      Systolic pressure, respiration volume, minute respiration volume and peak
      expiration rate were shown to be the most labile characteristics of the
      cardiorespiratory system responding by increases on magnetodisturbed days. The
      parameters under study exhibited sexual and age differences equally on quiescent
      and magnetodisturbed days. Adaptation to growing tension of the magnetic field of
      Earth involves the neuroendocrine system and manifests itself by activation of
      the sympathetic nervous system entailing relative shifts in the cardiorespiratory
      parameters under study.

PMID- 11840872
TI  - [Technology of biological management of plant and animal wastes].
AB  - Analytical, research and design efforts were made to modify the technology of
      anaerobic fermentation of plant and animal wastes. Results were publication of a
      register of wastes of a middle size Russian town, development of a simulator of
      natural food wastes, and development and testing of a laboratory prototype of
      original system for anaerobic degradation of natural food wastes. It was shown
      that association of Clostridia and lactobacilli is best to initiate and implement
      the first phase of biodegradation of natural wastes.

PMID- 11840873
TI  - [Recovered water mineralization technique].
AB  - The possibility to mineralize water by metering out concentrated salt solutions
      in the amounts necessary to bring it to within the potable water standards with
      intermediate exchange of chlorine ions for bicarbonate-ions has been
      demonstrated. The proposed technique ensures physiological quality and stability
      of recovered water mineralized with solutions of inorganic salts. Stability of
      concentrated salt solutions kept in metering syringes and potable water was
      evaluated. Organoleptic tests of resultant potable water were conducted.

PMID- 11840874
TI  - [Normal values of optokinetic nystagmus during mono- and binocular panorama
      stimulation].
AB  - Optokinetic nystagmus was studied in 20 normals (14 females and 6 males) aged
      from 23 up to 35 with the use of mono- and binocular panorama stimulation (a 1.5
      m optokinetic cylinder) with the intensity of 0.67, 1.33 and 2 Hz. In normal
      subjects, the coefficient of OKN amplitude asymmetry was equal to 6% and the
      coefficient of slow phase velocity was 7.7%. None of the subjects displayed
      inversion, i.e. change in nystagmus direction for opposite. Temporal nasal
      asymmetry in adult subjects was not registered either.

PMID- 11840875
TI  - [Morphological reactivity of neurons following chronic exposure to wide-range
      electromagnetic impulses].
AB  - In an experiment with white nubilous male rats the morphofunctional state of
      neurons in the cerebral hemisphere cortex was evaluated with the morphological
      and statistical methods following electromagnetic exposure (500 impulses once a
      week for 5, 7 and 10 mos.) inducing in the animal body the averaged current
      densities of 0.21 and 1.5 kA/m2. Chronic exposure to electromagnetic fields with
      the density of 0.21 kA/m2 was found to increase the biosynthetic activity of
      neurons by way of compensation and adaptation and level at the end of experiment,
      whereas the density of 1.5 kA/m2 brings about profound structural and functional
      disorders in and inhibits the biosynthetic activity of the neurons.

PMID- 11840876
TI  - [The concept of the use of information complexes of the Russian space industry in
      the telemedicine program].

PMID- 11840877
TI  - [Computerized analysis of graphic information in Telemedicine projects].

PMID- 11840878
TI  - Health promotion strategies an other clinical issues in spina bifida.
AB  - A routine approach to reviewing spina bifida helps clinicians detect problems
      requiring early treatment and referral.  In addition, information, such as
      dietary and other lifestyle information can help promote a sense of health
      wellbeing.

PMID- 11840880
TI  - Organizations and further resources.
AB  - Local organizations can put you into contact with specialist centres and other
      resources in your area.

PMID- 11840879
TI  - Sexuality and reproductive issues.
AB  - Managing issues of incontinence inevitably raises issues of sexuality.  The
      complications of spina bifida that affect urinary and bowel function also affect
      sexual functioning.  Routine review requires regular assessment of sexual issues
      while taking into account any special needs.  This chapter highlights some of the
      common issues general practitioners need to know when treating people with spina
      bifida.

PMID- 11840881
TI  - An approach to adolescent drug use.
AB  - BACKGROUND: Substance abuse is one of the most challenging and emotionally
      charged areas of general practice as it is in society at large. When this is
      combined with some of the difficulties in engaging the adolescent patient, it is
      not uncommon for the general practitioner to feel overwhelmed and unsure about
      how to approach the issue. OBJECTIVE: This article discusses strategies for GPs
      in managing adolescent patients with substance abuse, including referral services
      and opportunities for collaboration and a team approach. DISCUSSION: While there
      are good reasons to be concerned about substance abuse among adolescents and
      uncertainty about where to turn for specialised help, there is much the GP can do
      alone, and in collaboration with other services, to care for the adolescent with
      a substance use issue.

PMID- 11840882
TI  - Naltrexone for opioid dependence. An additional tool for general practitioners.
AB  - BACKGROUND: For over two years, naltrexone has been available as a treatment for
      opioid dependence. It is a useful addition to the limited range of available drug
      treatments. OBJECTIVE: This article outlines the major pharmacological features
      of naltrexone and provides some guidelines on its use in opioid dependence for
      general practitioners. DISCUSSION: In the past, options for GPs in assisting
      opioid dependent patients have been limited, and referral to alcohol and drug
      programs has usually been the most practical response. Over the past five years
      there has been a significant increase in the range of available treatments. One
      relatively recent addition to the options is the drug naltrexone (Revia) which
      can be used by the GP with rewarding results if patients are carefully chosen and
      safety guidelines for the drug are adhered to.

PMID- 11840884
TI  - Lipid lowering agents. How important are they in secondary prevention of coronary
      heart disease?
AB  - BACKGROUND: Coronary heart disease (CHD) is still the single major cause of death
      in our community despite the dramatic decline in prevalence over the past 20
      years or so. The first presentation of CHD in up to 50% of patients is one of the
      acute coronary syndromes, either acute myocardial infarction or unstable angina.
      Ninety percent of patients survive the acute episode and remain at high risk of
      further coronary events. OBJECTIVE: To review recent evidence regarding the
      importance of lipid lowering in preventing further coronary events--secondary
      prevention. DISCUSSION: The statins ushered in a new era of CHD prevention. Their
      discovery facilitated an enormous amount of basic research regarding pathogenesis
      of atherosclerosis and huge clinical trials that demonstrated dramatic reduction
      of vascular events and improved survival. Lipid lowering is central to secondary
      prevention in CHD and almost all patients who have had an acute coronary event
      benefit from statin therapy.

PMID- 11840885
TI  - Opioid dependence. Are pharmacotherapies effective?

PMID- 11840883
TI  - Smoking cessation in schizophrenia. General practice guidelines.
AB  - BACKGROUND: The rate of cigarette smoking in people with schizophrenia is up to
      three times that of the general population, and causes much ill health and high
      mortality rates. There are physiological and pharmacological interactions between
      the symptoms of schizophrenia, antipsychotic medication and smoking which
      contribute to this high rate and make it more difficult for those with
      schizophrenia to cease smoking. OBJECTIVE: This article aims to inform general
      practitioners of the extent and nature of the problem, and ways to assist people
      with schizophrenia to reduce/cease smoking. DISCUSSION: Patients with
      schizophrenia often experience physical, financial and social disadvantages
      because of their illness. Actively encouraging and assisting smoking
      reduction/cessation is important to improve their quality of life as well as
      longevity.

PMID- 11840886
TI  - Balint groups. Examining the doctor-patient relationship.
AB  - BACKGROUND: The psychological care of patients in a general practice setting is
      an important issue, and one currently receiving attention, as are the problems of
      stress and the mental health of general practitioners. Balint groups have been
      effectively used to assist in these domains. OBJECTIVE: To describe the
      functioning of Balint groups as they were originally developed, and review the
      findings that have arisen from them concerning the nature of general practice and
      the doctor-patient relationship and to examine the role Balint groups can play in
      modern general practice. DISCUSSION: Balint groups are a way of helping doctors
      reflect upon their style of relating to patients. This helps in gaining a deeper
      understanding of patients and their needs. At the same time, Balint groups
      facilitate understanding of the uncertainties of medical practice, reducing GP
      stress and increasing work satisfaction. Balint groups make a useful contribution
      to general practice CME, helping GPs to be receptive to the psychological needs
      of patients and facilitating the understanding and management of difficult cases.

PMID- 11840887
TI  - Doctor as patient. Part 1: When the unexpected happens.
AB  - The folk philosophers will tell you the job that is put off is the one that takes
      longest to finish. The psychologists will verify the benefit of committing one's
      thoughts to paper as a way of exorcising the ghosts of the past. These two
      sentiments are by way of an explanation as to why this story needs to be written
      and why it has taken so long to get round to it. The years in between have
      allowed some of the ghosts to assume manageable proportions, that is to say they
      might now be managed as opposed to denied. This tale, while being an objective
      record of some of the events of late 1988, is also a record of some of the
      feelings attached to those events--a more difficult task.

PMID- 11840888
TI  - Medical fees. Lodge practice.
AB  - Paying the doctor often imposed a severe financial burden on patients. Various
      ways were devised to help patients to access medical care. One such way to pay
      the doctor was through Friendly Societies. This article looks at the role of
      these groups in medical practice.

PMID- 11840889
TI  - Factors influencing career development of Australian general practitioners.
AB  - OBJECTIVE: To evaluate factors influencing career experiences and career choices
      made by former general practitioner registrars and to ascertain the reasons for
      these career decisions. METHOD: A postal questionnaire was sent to all former
      registrars who completed the RACGP Training Program between 1994 and 1996. In
      addition 21 selected respondents were interviewed to obtain deeper insights into
      the comments recorded in returned questionnaires. All data were analysed for
      variance according to age, gender, state and locality of current general practice
      (i.e. whether metropolitan, rural or remote). RESULTS: Altogether, 472 of the 988
      questionnaires distributed were completed and returned. Of the respondents, 62.3%
      were female and 36.4% male; 68% were aged 30-34 years. Most (85.4%) lived with a
      partner, and 53.8% had at least one child. The majority (87.9%) of respondents
      gained their primary medical qualification in Australia. In addition to the
      FRACGP, 35.6% had also gained a Diploma of Obstetrics and Gynaecology. A number
      of other qualifications were recorded. Three-quarters (75.6%) of participants
      were currently working as group GPs, two-thirds of whom were employees; 5.9% were
      solo GPs; 3.4% locums; and 1.3% rural hospital medical officers. About one-third
      (32.4%) held a second job; most of these were in subspecialty clinics or
      attachments. Sixty-six percent were currently in metropolitan practice, 17.6% in
      rural and 2.7% in remote practice. The two highest ranked career options were
      continued professional development (70.8%) and performance of minor procedures
      (67.2%). Family and domestic circumstances stood out as the most influential
      factor for 79.0% of GPs. The majority (75.8%) felt that vocational training had
      exerted a positive effect on their careers through, for example, exposure to
      varied practice types and good overall clinical training. CONCLUSION: While
      general practice experience in undergraduate education is an important factor in
      career choice, vocational training strongly influences preparation for, and the
      type of general practice undertaken. Nevertheless, family circumstances were
      reported as the most important consideration, although male and female work
      patterns differed markedly. It is concluded that these differences reflect
      different priorities in balancing professional and personal demands. The
      particular needs of the growing proportion of female practitioners have strong
      implications for future educational and workforce planning.

PMID- 11840890
TI  - Chronic illness care as a balancing act. A qualitative study.
AB  - OBJECTIVE: Current health care reforms aim to assist general practitioners in
      providing chronic illness care. This study investigates GPs' models of care
      including their role and responsibilities and their delivery of care models.
      METHODS: Sixteen GPs, as key informants representing diverse backgrounds, were
      interviewed about their general chronic illness care and responses to case
      vignettes. Thematic analysis was based upon the categorizing of GP interviews.
      RESULTS: The key responsibility in GP models of care was to address the
      presenting problem and to manage disease and treatment. Models encompassed
      providing preventive and psychosocial care; and care coordination, but in
      relation to need as time permitted. Experience and education, rather than reforms
      and incentives shaped care models. While patient-centredness was a universal
      theme, gender and location influenced its implementation. Care delivery was an
      individualized balance of patient needs with other pressures over a series of
      consultations. DISCUSSION: General practitioners balance models of care with
      organisational and resource constraints in everyday consultations. Consistent
      common models of care are subjected to a wide range of influences and translated
      into varied modes of service delivery and presumably patient outcomes.
      CONCLUSION: Reforms to improve outcomes for people with chronic illness must
      address GP care models and adaptive balancing of needs and resources and
      recognise internal and external constraints that encroach upon patient centred
      comprehensive care. Policymakers need to research and consult in order that
      reforms can realistically facilitate care.

PMID- 11840891
TI  - Bier's block and fasting.

PMID- 11840892
TI  - Participating in end of life decisions. The role of general practitioners.
AB  - BACKGROUND: 'Advance directives' are instructions given by an individual
      regarding future health care decisions should they become incapacitated. AIM: To
      explore the issues for GPs when introducing advance directives to their patients
      as a basis for further research into this process. METHOD: Interviews with GPs
      before and after the introduction of advance directives to patients during a
      normal consultation. General practitioners, from two medical practices in South
      Australia, were asked to record demographic details, time taken, patient's
      reaction and information requested. RESULTS: Five GPs introduced advance
      directives to 26 patients. The average age was 77 years. Six of the 26 patients
      completed an advance directive. The main issues identified when introducing
      advance directives were the time factor and difficulty in advising patients about
      the kinds of medical treatment they might want to record in advance. DISCUSSION:
      General practitioners require time and information if they are to assist patients
      in the process of completing an advance directive. Further research and extensive
      public education are necessary to develop relevant strategies to encourage the
      use of advance directives if they are to be utilised to assist people to face
      death with some sense of control.

PMID- 11840893
TI  - Spina bifida. Key primary issues.
AB  - Spina bifida is a static congenital neural tube disorder resulting in continuing
      evolving disease involving multiple organ systems.  Those affected require
      lifelong surveillance with coordinated management involving the patient, parents,
      general practitioners, neurologists, physiotherapists, occupational therapists,
      social workers, nurses, neurosurgeons, urologists, orthopaedic surgeons,
      physicians and other health professionals.

PMID- 11840894
TI  - Breast self examination.

PMID- 11840895
TI  - The spinal cord and brain in myelodysplasias.
AB  - This chapter defines various neurological abnormalities and terms specific to the
      management of spina bifida and related disorders..

PMID- 11840896
TI  - The impact of hydrocephalus and other CNS conditions on case management.
AB  - Hydrocephalus affects most people with spina bifida and can impact upon
      continence management adversely in two main areas.  Firstly, increased
      intracranial pressure can cause a deterioration of  continence and mental status,
      which sometimes can be insidious and at other times dramatic.  Secondly, the
      effect of cognitive deficits secondary to central nervous system abnormalities
      can be subtle, but can be a profound barrier to achieving successful case
      management, including continence control and independent living.

PMID- 11840897
TI  - Substance abuse in teenagers. Trends and consequences.
AB  - BACKGROUND: Over the past few decades there has been growing concern about the
      use and abuse of alcohol and other drugs by adolescents. OBJECTIVE: To outline
      the trends in and consequences of adolescent substance abuse. DISCUSSION: Alcohol
      and tobacco remain the most often used drugs in adolescence, and are the drugs
      associated with greatest morbidity and mortality, but there is some evidence that
      the use of illicit drugs is increasing. Morbidity and mortality from substance
      abuse can occur directly from the effects of the drug, from the mode of
      administration or from environmental factors associated with drug use. Drug
      related deaths compromise 24% of all deaths in the 12-24 year old age group. This
      is likely to be an underestimate as alcohol related traffic accidents are
      excluded from this figure.

PMID- 11840898
TI  - Spinal cord tethering.
AB  - Tethering of the spinal cord is an insidious cause of worsening incontinence that
      requires urgent medical assessment and possibly surgical intervention to prevent
      any further deterioration.  Clinicians monitoring young people and adults with
      spina bifida need to maintain a high degree of suspicion to ensure the early
      detection of tethered cord syndrome to help promote and maintainindependent
      living.

PMID- 11840899
TI  - Urological management of spina bifida (including management of urinary tract
      infections).
AB  - Active and ongoing surveillance for urological problems helps to minimize the
      impact of the major source of mortality and morbidity in spina bifida.

PMID- 11840900
TI  - Controlling urinary incontinence.
AB  - Achieving control of urinary continence is the key to achieving an independent
      lifestyle.  A wide range of interventions and resources exist to assist in the
      successful management of urinary incontinence.  This chapter provides the
      clinician with and introduction to management principles, some resources and also
      outlines the roles o specialist clinics in the management of incontinence ( for
      issues of faecal incontinence, see chapter 6)..

PMID- 11840901
TI  - Medicaid patients in a private health maintenance organization: patterns of
      chemical dependency treatment.
AB  - Although many Medicaid beneficiaries receive health care through commercial
      health maintenance organizations (HMOs), the impact of private managed care on
      low-income individuals seeking treatment for substance abuse has rarely been
      studied. This study examined treatment patterns of 234 Medicaid recipients who
      presented for care at an HMO between 1995 and 1997. After adjustment for
      demographic factors and duration of health plan membership, the Medicaid patients
      returned to start treatment after intake less often (odds ratio = 0.60) and
      dropped out of treatment sooner (median = 14 versus 28 days) than non-Medicaid
      patients. While many Medicaid patients received significant amounts of substance
      abuse treatment, further research is needed to explain the observed treatment gap
      and to identify areas where HMOs can improve services for some of their most
      vulnerable members.

PMID- 11840902
TI  - Access to new medications to treat schizophrenia.
AB  - Between 1989 and 1997, the Food and Drug Administration approved four new
      generation antipsychotic medications for use in the treatment of schizophrenia.
      This article examines factors associated with the use of new antipsychotic
      medications as compared with traditional antipsychotic medications from patient
      interviews, medical records, and a physician survey administered at schizophrenia
      treatment sites around the country as part of the Schizophrenia Care and
      Assessment Program. The following variables were significantly associated with a
      higher probability of receiving an atypical antipsychotic medication in multiple
      regression analysis at p < .05: female, younger age, younger age of onset, non
      African American, having a higher Positive and Negative Syndrome Scale-Negative
      Syndrome subscale score. Some physician characteristics were statistically
      significant in the bivariate results but not in the multivariate analyses. Access
      to new atypical antipsychotic medications is dependent on more than clinical
      characteristics. In particular, barriers to access may exist for African
      Americans. Physician access to information about advances in drug therapies also
      may play a substantial role in the rate of diffusion of new medications.

PMID- 11840905
TI  - Utilization and cost of behavioral health services: employee characteristics and
      workplace health promotion.
AB  - The study sought to (1) model demographic and employment-related influences on
      behavioral health care utilization and cost; (2) model behavioral health care
      utilization and cost influences on general health care cost, job performance, and
      earnings; and (3) assess workplace-based health promotion's impact on these
      factors. Behavioral health care utilization was more common in employees who were
      female, over age 30, with below-median earnings, or with above-median general
      (non-behavioral) health care costs. Among employees utilizing behavioral health
      care, related costs were higher for employees with below-median earnings.
      Employees utilizing behavioral health care had higher general health care costs
      and received lower performance ratings than other employees. Health promotion
      participants were compared with a nonparticipant random sample matched on gender,
      age, and pre-intervention behavioral health care utilization. Among employees
      without pre-intervention behavioral health care, participants and nonparticipants
      did not differ in post-intervention utilization. Among employees utilizing
      behavioral health care adjusting for pre-intervention costs, participants had
      higher short-term post-intervention behavioral health care costs than
      nonparticipants.

PMID- 11840903
TI  - Prevalence of alcohol and drug use in a highly educated workforce.
AB  - This study examined alcohol and licit and illicit drug use in a highly educated
      workforce. A comprehensive health survey of a 10% random sample of a workforce (n
      = 8,567) yielded a 60% response rate (n = 504) after accounting for 15
      undeliverable surveys. Many respondents reported past-year use of alcohol (87%).
      Thirteen percent of respondents consumed three or more drinks daily; 15% were
      binge drinkers. Twelve percent of the workforce was assessed as having a high
      likelihood of lifetime alcohol dependence; 5% of respondents met criteria for
      current problem drinking. Overall, 42% reported using mood-altering prescription
      drugs (analgesics, antidepressants, sedatives, or tranquilizers). Eleven percent
      reported using illicit drugs (cocaine, hallucinogens, heroin, or marijuana) in
      the past year. Significant relationships were found between gender, age,
      ethnicity, and occupation with some measures of alcohol consumption and use of
      mood-altering drugs. These results indicate prevention and early intervention
      programs need to address use of mood-altering substances (including alcohol) in
      highly educated workforces.

PMID- 11840904
TI  - Referral sources, diagnoses, and service types of youth in public outpatient
      mental health care: a focus on ethnic minorities.
AB  - Racial/ethnic variations in clinical and service delivery characteristics among
      youth in public outpatient mental health services were examined using data from
      San Diego County mental health service programs for fiscal year 1996 to 1997 (N =
      3,962). Differences in referral sources, primary diagnoses, and service types
      were investigated for three racial/ethnic groups (African Americans,
      Asian/Pacific Islander Americans, and Latinos) compared to non-Hispanic whites.
      Controlling for age, gender, functional impairment, and prior service use,
      significant differences by race/ethnicity were found for all three variables
      studied. Possible explanations for these variations and future directions for
      research are discussed.

PMID- 11840906
TI  - Use of measurement audit in outcomes management.
AB  - With the growing emphasis on accountability in mental health services, outcomes
      management strategies are gaining popularity. However, for these techniques to be
      credible, it is necessary to ensure the reliability of clinical data. In other
      words, outcomes measures must accurately reflect the actual status of service
      recipients. This article presents the use of the measurement audit as one means
      of monitoring and improving the reliability of outcomes measurements. The methods
      and findings from an audit of crisis assessment workers for children in state
      custody are presented. Clinical assessments completed at the time of service were
      compared with assessments using the same measure completed via retrospective file
      review. Findings suggest generally good reliability, 0.72 overall, with some
      variation by provider and type of information.

PMID- 11840907
TI  - Issues related to combining risk factor reduction and clinical treatment for
      eating disorders in defined populations.
AB  - Population-based psychotherapy considers the provision of services to a
      population at risk for or already affected with a disease or disorder. Using
      existing data on prevalence, incidence, risk factors, and interventions (both
      preventive and clinical) for eating disorders (anorexia excluded), this article
      examines issues related to integrating and providing risk reduction and treatment
      to a population of female college students. Population-based psychotherapy models
      have important implications for the provision of services and for future
      directions in research on eating and other types of mental health disorders, but
      the assumptions need to be carefully examined. Studies that provide data
      combining population-based risk factor reduction and clinical treatment are
      needed to advance this field.

PMID- 11840908
TI  - Mental health service use and cost of care for older adults in assisted living
      facilities: implications for public policy.
AB  - With changing demographics prompting greater demand for assisted living facility
      (ALF) care, indigent older adults with mental health needs face underfunded
      residential care options and mental health systems currently unprepared to meet
      their service requirements. In particular, over-reliance on inpatient mental
      health services for older individuals with mental illness and inadequate
      reimbursement of ALF facilities potentially increase costs and threaten
      availability of ALF care. This article analyzes Florida's administrative data and
      presents findings on mental health service use and cost of care for poor older
      persons. Using Florida as an example, the authors recommend policy changes to
      ensure the quality and availability of residential care for low-income adults
      with mental health needs.

PMID- 11840910
TI  - Dermatology.

PMID- 11840911
TI  - Emergency medicine.

PMID- 11840912
TI  - Endocrinology.

PMID- 11840909
TI  - The effect of technical support on clinician attitudes toward an outcome
      assessment instrument.
AB  - This study evaluated the impact of technical support on mental health clinicians'
      attitudes and use of an outcome assessment (OA) instrument. Technical support
      involved providing clinicians with the scored and profiled results of an OA
      instrument administered to their patients. It was predicted that temporary
      exposure to the instrument's uses would improve clinicians' attitudes toward the
      instrument and that improved attitudes would lead to greater use. The results
      indicated that subsequent to support clinicians' attitudes toward the instrument
      were generally more positive, as they had generally more favorable opinions, saw
      it as more relevant, and reported that it was relatively easy to use. Contrary to
      expectations, however, clinicians did not use the OA instrument more frequently
      or regularly after support. The implications for clinics seeking to implement OA
      protocols are discussed.

PMID- 11840913
TI  - Forensic pathology.

PMID- 11840914
TI  - Gastroenterology and hepatology.

PMID- 11840915
TI  - Gastrointestinal surgery.

PMID- 11840916
TI  - General internal medicine.

PMID- 11840917
TI  - General practice.

PMID- 11840918
TI  - Genetics.

PMID- 11840920
TI  - Surveying the specialist silos.

PMID- 11840919
TI  - Haematology.

PMID- 11840921
TI  - Health informatics.

PMID- 11840922
TI  - HIV medicine.

PMID- 11840923
TI  - Immunology and allergy.

PMID- 11840924
TI  - Infectious diseases.

PMID- 11840925
TI  - Intensive care medicine.

PMID- 11840926
TI  - Medical oncology.

PMID- 11840927
TI  - Neurology and neurosurgery.

PMID- 11840928
TI  - Nuclear medicine.

PMID- 11840929
TI  - Obstetrics and gynaecology.

PMID- 11840930
TI  - Ophthalmology.

PMID- 11840931
TI  - Adolescent medicine.

PMID- 11840932
TI  - Orthopaedics.

PMID- 11840933
TI  - Otolaryngology/head and neck surgery.

PMID- 11840935
TI  - Palliative medicine.

PMID- 11840934
TI  - Paediatrics and paediatric surgery.

PMID- 11840936
TI  - Plastic surgery.

PMID- 11840937
TI  - Psychiatry.

PMID- 11840938
TI  - Public health.

PMID- 11840939
TI  - Radiation oncology.

PMID- 11840940
TI  - Radiology.

PMID- 11840941
TI  - Renal medicine.

PMID- 11840942
TI  - Aged-care medicine.

PMID- 11840943
TI  - Respiratory medicine and thoracic surgery.

PMID- 11840944
TI  - Rheumatology.

PMID- 11840945
TI  - Urology.

PMID- 11840946
TI  - Vascular surgery.

PMID- 11840947
TI  - Alcohol and drugs.

PMID- 11840948
TI  - Anaesthesia.

PMID- 11840949
TI  - Anatomical pathology.

PMID- 11840950
TI  - Cardiology and cardiac surgery.

PMID- 11840951
TI  - Clinical pharmacology.

PMID- 11840952
TI  - Sharing scientific development as an alternative to the brain drain.

PMID- 11840953
TI  - The myth of technology in health care.
AB  - Technology is believed to have liberated health care from dogmas, myths and
      speculations of earlier times. However, we are accused of using technology in an
      excessive, futile and even detrimental way, as if technology is compelling our
      actions. It appears to be like the monster threatening Dr. Frankenstein or like
      the sorcerer's broom in the hand of the apprentice. That is, the same technology
      that should liberate us from myths, appears to be mythical. The objective of this
      article is to investigate the background for the re-entrance of the myth: How we
      encounter it and how we can explain it. The main point is that a myth of
      technology is normative: it relates 'is' and 'ought' and directs our actions.
      This becomes particularly clear in health care. Hence, if there is a myth of
      technology, it is an ethical issue, and should be taken seriously.

PMID- 11840954
TI  - Science and technology for the good of society?

PMID- 11840955
TI  - Apologizing for the past: German science and Nazi medicine.
AB  - Recently, religious organisations, governments and public institutions have begun
      to offer apologies for historical wrongs. Can they legitimately do so? Departing
      from the tendency, Professor Hubert Markl, President of the Max Planck Society,
      has offered strong reasons for not apologizing for the crimes of medical
      scientists who experimented on human subjects during the Nazi era. He argues that
      only the perpetrators can meaningfully apologize. Markl's position is considered
      and rejected in favour of the view that apologies by proxy for historical wrongs
      are justifiable and should be made by institutions that have the authority to do
      so.

PMID- 11840956
TI  - Ethics and science: educating the public.
AB  - This article looks at the public debate which took place in the first half of the
      twentieth century and has repercussions to the present day. It was about the
      ethical stance of scientists, and how science should be organized. In particular,
      it examines the positions taken by Professor F. Soddy, F.R.S. and Nobel Laureate,
      who stressed the responsibility of scientists for the uses made of their
      research, Professor Michael Polanyi, F.R.S., who emphasised the obligation of
      scientists to the truth and the essential role of morality in the organization of
      science, and Professor J.D. Bernal, F.R.S., who insisted that science was
      practiced for utilitarian reasons and should be consciously developed for the
      good of society.

PMID- 11840957
TI  - International science and fair-play practices.

PMID- 11840958
TI  - Representation and misrepresentation: Tufte and the Morton Thiokol engineers on
      the Challenger.
AB  - This paper examines the role of the Morton Thiokol engineers in the decisions
      surrounding the launch of the Challenger, particularly with reference to an
      analysis of this event by Edward Tufte. The engineers at Morton Thiokol
      recommended against the launch of Challenger because the projected launch
      temperature between 26 degrees F to 29 degrees F was far outside their field
      database of successful launches. The engineers had asked for, but not received,
      data necessary to determine the cause of massive blow-by on the launch the
      previous January, and they had informed their managers and NASA that continuing
      flights could be catastrophic if the cause of the problems with the launches was
      not discovered. The authors conclude that the engineers thus did what they were
      ethically as well as professionally obligated to do.

PMID- 11840959
TI  - Diverse knowledges and competing interests: an essay on socio-technical problem
      solving.
AB  - Solving complex socio-technical problems, this paper claims, involves diverse
      knowledges (cognitive diversity), competing interests (social diversity), and
      pragmatism. To explain this view, this paper first explores two different cases:
      Canadian pulp and paper mill pollution and siting nuclear reactors in
      systematically sensitive areas of California. Solving such socio-technically
      complex problems involves cognitive diversity as well as social diversity and
      pragmatism. Cognitive diversity requires one to not only recognize relevant
      knowledges but also to assess their validity. Finally, it is suggested,
      integrating the resultant set of diverse relevant and valid knowledges determines
      the parameters of the solution space for the problem.

PMID- 11840960
TI  - Peer review and innovation.
AB  - Two important aspects of the relationship between peer review and innovation
      includes the acceptance of articles for publication in journals and the
      assessment of applications for grants for the funding of research work. While
      there are well-known examples of the rejection by journals of first choice of
      many papers that have radically changed the way we think about the world outside
      ourselves, such papers do get published eventually, however tortuous the process
      required. With grant applications the situation differs in that the refusal of a
      grant necessarily curtails the possible research that may be attempted. Here
      there are many reasons for conservatism and reservation as to the ability of a
      grant allocation process based on peer review to deliver truly innovative
      investigations. Other methods are needed; although such methods need not be
      applied across the board, they should constitute the methods whereby some 10-20%
      of the grant monies are assigned. The nomination of prizes for specific
      accomplishments is one way of achieving innovation although this presumes that
      investigators or institution already have available the money necessary to effect
      the innovations; otherwise it is a question of the selection and funding of
      particular individuals or institutions and requiring them to solve particular
      problems that are set in the broadest of terms.

PMID- 11840961
TI  - [Involvement of dopamine in amplification of cortical signals activating NMDA
      receptors in the striatum (hypothetic mechanism)].
AB  - Possible mechanisms of amplification/attenuation of cortical signals opening or
      not opening NMDA-channels in striatal spine cells while passing through basal
      ganglio-thalamocortical network and relegated to either "strong" or "weak"
      signals, are considered. In absence of dopamine, a relative increase in intensity
      of the "strong" or "weak" cortical signals should result in the LTP/LTD on both
      striatonigral and striatopallidal cells, the thalamic cells being affected in the
      opposite way. Activation of the dopamine receptors on the striatonigral
      (striatopallidal) cells prompts the LTP/LTD expression. Thereof, the "strong"
      cortical signals are synergistically amplified whereas the "weak" signals are
      synergistically attenuated at the thalamic output.

PMID- 11840962
TI  - [Effect of a dopamine agonist on working memory in monkeys].
AB  - Prior to and after pharmacological effect of Agroclavine (a dopamine receptors'
      agonist) following its per os administration, its optimal dose (5 mg/kg) for
      cognitive processes was established in monkeys. Psychotropic effect of
      Agroclavine resulting in cognitive dysfunction manifested itself to a greater of
      lesser extent in all the experimental animals. Correctness of visual
      differentiation, probability of refusal to solve a task, time of a correct motor
      response were assumed as the behavioural criteria. In fact, all the animals
      revealed absence of any increase in the number of wrong solutions in visual
      differentiation or spatial choice, although the time of correct morot response
      and the number of refusal to solve the task mostly increased. The Agroclavine
      effect was found to be rather variable in respect to different types of visual
      information. A possible structural-functional organisation of the working memory
      processes is discussed.

PMID- 11840963
TI  - [Localization of corticoliberin receptors in the rat brain].
AB  - Using the in situ hybridization, a distribution of corticotropin-releasing
      hormone (CRH) receptors CRH-1 and CRH-2 in the rat brain has been studied. Brain
      levels of CRH-1 mRNA were higher than the those of CRH-2 mRNA. Most intensive CRH
      1 gene expression was observed in the forebrain, including neocortex,
      archicortex, paleocortex and cerebellar cortex. In addition, significant CRH-1
      mRNA expression was detected in the red nucleus, pontine nucleus, cochlear
      nucleus and reticular tegmental nucleus. CRH-2 mRNA was intensively expressed in
      the olfactory structures, corticomedial amygdala, CA1-CA4 of hippocampus,
      ventramedial hypothalamus and several modullar nuclei. Moderate CRH-2 mRNA level
      were seen in the dorsomedial neostriatum. The findings indicate that within the
      brain two types of CRH receptors are widely expressed. A distinct pattern of CRH
      1 and CRH-2 expression in the brain appears to underline the functional specifics
      of the CRH actions in brain structures.

PMID- 11840964
TI  - [Hemodynamic mechanisms of blood flow regulation in the vena cava anterior].
AB  - A similarity of the blood flow shifts in response to every single pressor or
      depressor stimulus in the v. cava anterior in cats and a possibility of
      dissimilar changes of capacity of the vein's vascular basin under the effect of
      one and the same stimulus, are revealed. This dissimilarity is mainly due to a
      skin-muscular component of this vascular basin. An increase in the central venous
      pressure from 0 to 40 mm of water limits the extent of shifts in the capacity
      function of the v. cava anterior's basin. The blood flow changes in the v. cava
      anterior is mainly due to a relationship among regional components of the
      vessels' total peripheral resistance. A potential possible contribution of the v.
      cava anterior basin vessels capacitance's shifts constitutes 17.5%, whereas under
      the effect of neurogenic stimuli in the increase of the blood flow in the v. cava
      anterior may be completely (up to 100%) maintained by a drop of the capacitance
      of the vein's vascular basin.

PMID- 11840965
TI  - [Effect of emotional stress on the cardiac rhythm variability in rats].
AB  - A degree of irregularities of the heart rhythm was studied by two methods: chaos
      analysis and the HRV (heart rate variability) analysis. Our study shows an
      individual response in 3 groups of animals: 1--animals with low initial level of
      chaos (correlation dimension (PD2 < 2); 2--animals with high level of chaos (PD2
      > 4); and animals with middle level of chaos (2 < PD2 < 4). The first two groups
      proved to be more sensitive to stress than the third group. Moreover we found
      that the electrical stability of the heart as measured by the fibrillation
      threshold, was higher for the chaos third group. The animals of the first two
      groups had low cardiac stability and high risk of stress-induced cardiac
      disturbances.

PMID- 11840966
TI  - [Changes in alpha1-, alpha2-, and beta-adrenergic responses of blood pressure in
      blood vessels of the rabbit hindlimbs during cold adaptation].
AB  - Changes in major parameters of alpha 1-, alpha 2- and beta-adrenergic responses
      (EC50 and Pm) were studied in hind-limb arterial vessels of the rabbits adapted
      to cold for 1-30 days (daily cold exposures for 6 hours at -10 degrees C). It was
      shown that responses to phenylephrine, noradrenaline, adrenaline (alpha 1
      agonists), clondine (alpha 2-agonist), isopropylnoradrenaline (beta-agonist)
      corresponded to the equation p = (Pm.An)/(EC50n = An) with n = 1 and n = 2,
      respectively. Adaptation to cold induced radically different changes in the major
      parameters of alpha- and beta-adrenergic responses. In the alpha-adrenergic
      responses, the parameters EC50 and Pm changed reciprocally. In the beta
      adrenergic response, only the Pm value changed while EC50 did not differ from the
      control over the entire period of adaptation to cold. The pronounced differences
      from the control gradually decreased within 1-5 days of adaptation but remained
      significant until the 30th day.

PMID- 11840967
TI  - [Morphofunctional changes in the pineal gland during adaptation to hypothermia].
AB  - The influence of hypothermal stress (+4 degrees during 3 h) on the ways of
      serotonin metabolism in pineal gland and its structure has been studied in
      dynamics on adult male Wistar rats. It has been revealed that melatonin-producing
      epiphyseal function suffers from phase changes in dynamics of adaptation-
      significant rising during 15 min. after beginning of the experiment,
      rehabilitation up to normal--in 30 min, and fast suppressing--in 3 hrs.
      Suppressing of the functional pineal activity is not due to switched serotonin
      metabolism with melatonin and new indoles release, but to a partial pinealocytes
      breaking from their active function.

PMID- 11840969
TI  - [Contractile responses of the myoepithelial cells of the mouse mammary gland in
      situ].
AB  - In experiments on laboratory mice in situ, a contractile response of the mammary
      gland's myoepithelial cells was electromechanically studied. A gradual response
      to oxytocin application, with a relatively fast front of contraction and a
      prolonged relaxation period, was recorded. The contraction time up to the maximum
      was 8.5 s, the relaxation period--31 s. In many experiments (73%), following a
      single oxytocin application, a few successive contractions of the alveola were
      registered. The high velocity of the myoepithelium contraction maintains a
      necessary pressure for fast transport of the secret within the ducts. The
      contraction low velocity as well as appearance of new myoepithelium contraction
      waves creates conditions for keeping the secret within the ducts, extending the
      time when the litter can receive the feeding.

PMID- 11840968
TI  - [Neurite-stimulating activity of secretions from the Hirudo medicinalis salivary
      gland in cultured sensory neurons].
AB  - Components of leech (Hirudo medicinalis) salivary gland secretion (high molecular
      mass bdelin B, bdellastasin, eglin C, destabilize) were used to investigate their
      neurotrophic effect on organotypic culture of dorsal root ganglia of the 10-11
      day old chicken embryos. Destabilize and high molecular mass bdelin B in
      concentrations of 0.01, 0.02, 0.05 and 0.1 ng/ml, bdellastasin in concentrations
      of 0.02 and 0.05 ng/ml, eglin C in concentrations of 0.1 ng/ml exhibit neurite
      stimulating effect as compared to the control.

PMID- 11840970
TI  - [Various effects of prostaglandin E2 on reabsorption of water and urea in the
      amphibia osmosis-regulating epithelium].
AB  - Principal similarities between molecular pathways providing the enhancement of
      water and urea reabsorption under the action of argininvasotocin (AVT) in
      amphibian urinary bladder suggest that prostaglandin E2 (PGE2) could be a
      negative regulator of urea transport. To analyse this hypothesis, the role of
      PGE2 in regulation of urea transport was studied in isolated frog (Rana
      temporaria L.) urinary bladder. The urea permeability (Pu) was determined from
      the rate of efflux of (14) Curea from mucosal to serosal solution in isoosmotic
      conditions. The water permeability was measured in separate experiments in
      presence of an osmotic gradient. In contrast to water permeability, we were
      unable to demonstrate any inhibitory effect of 10-1000 nM PGE2 on AVT-stimulated
      urea transport using a variety of protocols. It was found that basolateral PGE2
      exposure (10 nM-1 microM) caused an increase in Pu with no effect on osmotic
      water flow. The PGE2 effect was markedly inhibited by phloretin, a specific
      inhibitor of urea transporter. Sulprostone, an EP1/EP3 prostaglandin E2 receptor
      agonist, had no effect on Pu suggesting the contribution of EP2/EP4 receptor
      subtypes. In presence of osmotic water flow, the AVT-induced urea transport was
      significantly higher. This water flow-dependent urea permeability was inhibited
      by PGE2 although the inhibitory effect was less pronounced in comparison to the
      action of PGE2 on osmotic water flow. On the basis of these results we can make a
      conclusion that PGE2 has different role in regulation of water and urea transport
      in the frog urinary bladder. PGE2 could be considered as a stimulator of urea
      transport and an inhibitor of osmotic water flow activated by the AVT. The
      ability of PGE2 to regulate various types of cAMP-dependent transport by
      different mechanisms seems to be based on the presence of multiple basolateral
      PGE2 receptor subtypes in amphibian osmosis-regulatory epithelium.

PMID- 11840971
TI  - [Effect of unilateral trauma of the sciatic nerve on characteristics of motor and
      reflex responses of paired gastrocnemius muscles].
AB  - The influence of unilateral n. ischiadicus lesion of conductivity on the
      electromyographic characteristics of the rat gastrocnemius muscles was
      investigated. The lesion was made by n. ischiadicus crashing. Motor and reflex
      gastrocnemius muscles' responses caused by n. ischiadicus stimulation (single
      impulses of various intensity and 0.3 ms duration) were estimated on broken and
      symmetric hind-limb before and 1, 5, 10, 20 and 30 days after the nerve crashing.
      Considerable changes of threshold and amplitude of the registered gastrocnemius
      muscle responses were observed ipsi- and contralaterally. It is suggested that
      the central dependence of processes arising in the motor centres of symmetric
      gastrocnemius muscles, follows unilateral n. ischiadicus lesion.

PMID- 11840972
TI  - [Role of sex steroids in development of anxiety in female mice].
AB  - Level of sex steroid hormones being changed throughout an estrous cycle
      influences physiological and behavioral features of female subjects. To test how
      estrogen and progesterone affect the anxiety level in mice the ovariectomy (OVX)
      followed by hormone treatment was carried out. After 1 week of recovery period
      estradiol benzonate (20 micrograms, s/c) was injected once a day during 7
      consequent days. By the 7th day in addition to EB injection progesterone (500
      micrograms, s/c) was also injected. Four hours later the mice were tested in
      elevated plus-maze to measure the anxiety level. Control animals were treated
      with sesame oil only. Behavioral data obtained demonstrate that the hormonal
      treatment altered anxiety state in experimental animals. In plusmaze paradigm, it
      has been demonstrated that progesterone-treated mice revealed the lowest level of
      open arm activity. In contrast, these mice showed the highest grooming activity
      as compared to other experimental groups. Immunohistochemical data on
      progesterone receptor (PR), immunoreactivity in brain have shown that the
      manipulation with different hormonal treatments modified the number of PR-ir
      cells in many brain areas. Our data suggest that sex steroid hormones play an
      important role in induction of anxiety level, as measured by elevated plus-maze,
      and this action might be partially mediated through the classical steroid
      receptors.

PMID- 11840973
TI  - Proceedings of the 14th European Congress of Radiology. March 1-5, 2002. Vienna,
      Austria.

PMID- 11840975
TI  - [Ovarian cancer: emerging problems. Proceeding of a meeting. Napoli, Italy, 10-12
      October 2000].

PMID- 11840974
TI  - Screening for viral markers in volunteer and replacement blood donors in West
      Africa.
AB  - BACKGROUND AND OBJECTIVES: West Africa is a highly endemic area for viral
      infections. The prevalence of five viral markers was determined in Ghanaian blood
      donors. MATERIALS AND METHODS: Replacement and volunteer blood donors were
      screened using enzyme immunoassays (EIAs) for hepatitis B surface antigen
      (HBsAg), human immunodeficiency virus antibodies (anti-HIV), HIV p24 antigen,
      human T-cell lymphocytotrophic virus-I and -II antibodies (anti-HTLV-I/II) and
      hepatitis C virus antibodies (anti-HCV). RESULTS: HBsAg was present at an equally
      high frequency (15%) in young volunteer (median age 18 years) and older
      replacement (median age 33 years) blood donors. In contrast, the prevalence of
      anti-HIV and anti-HCV was significantly higher in replacement blood donors (2.4
      and 0.3%, respectively, P < 0.001). HCV RNA was detected in 74 or 55% of
      seropositive donors, depending on the confirmatory criteria used. No p24 antigen
      positive/anti-HIV-negative donations were found. The prevalence of HTLV-I/II was
      generally low (0.5%). CONCLUSION: All blood donations should be screened for
      hepatitis B virus (HBV), HIV and HCV markers.

PMID- 11840977
TI  - Abstracts of the 10th Annual Meeting of the Japanese Society of Clinical
      Neuropsychopharmacology. Tokyo, Japan, 15-16 November 2000.

PMID- 11840978
TI  - [Proceedings of the 24th Seminar of Environmental Hygiene: Spread of pathogenic
      agents through handling and transportation of animals and animal products. 23
      February 2001, Hannover].

PMID- 11840979
TI  - Abstracts of the International School of Neurological Sciences 11th annual
      meeting of the child neurology section. Venice, Italy, September 28-29, 2001.

PMID- 11840980
TI  - Proceedings of the International Symposium "Update in Thrombolysis 2000:
      Arteriosclerosis, Thrombosis and Cardiovascular Biology". October 12-14, 2000,
      Vienna, Austria.

PMID- 11840982
TI  - The Genetic Effects on Aging Meeting III. Bar Harbor, Maine, USA. August 4-8,
      2000. Proceedings.

PMID- 11840983
TI  - Proceedings of the 2nd International Symposium on Free Radical and Vascular
      Biology of Diabetes. Seoul, Korea, 24-25 February 2000.

PMID- 11840984
TI  - Proceedings of the 6th Novo Nordisk Symposium on Treatment of Bleeding and
      Thrombotic Disorders. Copenhagen, Denmark, May 3-4, 2001.

PMID- 11840981
TI  - Abstracts of the 8th International Pituitary Pathology Meeting. October 5-9,
      2001. Greece.

PMID- 11840985
TI  - The fate of the haloacetates in drinking water--chemical kinetics in aqueous
      solution.

PMID- 11840986
TI  - Review of vinyl graft copolymerization featuring recent advances toward
      controlled radical-based reactions and illustrated with chitin/chitosan trunk
      polymers.

PMID- 11840987
TI  - Peroral route: an opportunity for protein and peptide drug delivery.

PMID- 11840988
TI  - Hydrides of the main-group metals: new variations on an old theme.

PMID- 11840989
TI  - Organoboranes as a source of radicals.

PMID- 11840991
TI  - "Let's twist again"--double-stranded, triple-stranded, and circular helicates.

PMID- 11840990
TI  - Palladium-catalyzed Reppe carbonylation.
AB  - PdX2L2/L/HA (A = weakly coordinating anion, L = phosphine) complexes are active
      catalysts in the hydroesterification of alkenes, alkynes, and conjugated dienes.
      Shell, the only major corporate player in the field, recently developed two very
      active catalyst systems tailored to the hydroesterification of either alkenes or
      alkynes. The hydroesterification of propyne with their Pd(OAc)2/PN/HA (PN = (2
      pyridyl)diphenylphosphine, HA = strong acid with weakly coordinating anion, like
      methanesulfonic acid) catalyst has been declared commercially ready. However,
      despite the significant progress in the activity of Pd-hydroesterification
      catalysts, further improvements are warranted. Thus, for example, activity
      maintenance still seems to be an issue. Homogeneous Pd catalysts are prone to a
      number of deactivation reactions. Activity and stability promoters are often
      corrosive and add to the complexity of the system, making it less attractive.
      Nonetheless, the versatility of the process and its tolerance toward the
      functional groups of substrates should appeal especially to the makers of
      specialty products. Although hydroesterification yields esters from alkenes,
      alkynes, and dienes in fewer steps than hydroformylation does, the latter has
      some advantages at the current state of the art. (1) Hydroformylation catalysts,
      particularly some recently published phosphine-modified Rh systems, can achieve
      very high regioselectivity for the linear product that hydroesterification
      catalysts cannot match yet. By analogy with hydroformylation, bulkier ligands
      ought to be tested in hydroesterification to increase normal-ester selectivity.
      (2) Hydroformylation is proven, commercial. Hydroesterification can only replace
      it if it can provide significant economic incentives. Similar or just marginally
      better performance could not justify the cost of development of a new technology.
      (3) Hydroesterification requires pure CO while hydroformylation uses syngas, a
      mixture of CO and H2. The latter is typically more available and less expensive
      (for industrial applications CO is most often separated from syngas). (4) The
      acid component of the hydroesterification catalyst makes the process corrosive.
      It would be desirable to develop new hydroesterification catalysts that do not
      require acid stabilizer/activity booster. Clearly, any new hydroesterification
      technology will directly compete with the hydroformylation route. This is
      especially true for olefin feeds, since both processes add one CO to the olefin,
      yielding oxygenates that can be converted into identical products. For some niche
      applications, like the production of MMA from propyne, hydroesterification seems
      to have an advantage as compared to hydroformylation due to the high activity and
      selectivity of the Pd(OAc)2/(2-pyridyl)diphenylphosphine catalyst. Since
      hydroesterification is an emerging technology, it is reasonable to assume that
      the potential for improvement is greater than in the mature hydroformylation. It
      is therefore possible that hydroesterification will become competitive in the
      future; thus, continued effort in the field is warranted.

PMID- 11840992
TI  - Synthetic applications of nonmetal catalysts for homogeneous oxidations.
AB  - Nonmetal oxidation catalysts have gained much attention in recent years. The
      reason for this surge in activity is 2-fold: On one hand, a number of such
      catalysts has become readily accessible; on the other hand, such catalysts are
      quite resistant toward self-oxidation and compatible under aerobic and aqueous
      reaction conditions. In this review, we have focused on five nonmetal catalytic
      systems which have attained prominence in the oxidation field in view of their
      efficacy and their potential for future development; stoichiometric cases have
      been mentioned to provide overview and scope. Such nonmetal oxidation catalysts
      include the alpha-halo carbonyl compounds 1, ketones 2, imines 3, iminium salts
      4, and nitroxyl radicals 5. In combination with a suitable oxygen source (H2O2,
      KHSO5, NaOCl), these catalysts serve as precursors to the corresponding oxidants,
      namely, the perhydrates I, dioxiranes II, oxaziridines III, oxaziridinium ions
      IV, and finally oxoammonium ions V. A few of the salient features about these
      nonmetal, catalytic systems shall be reiterated in this summary. The first class
      entails the alpha-halo ketones, which catalyze the oxidation of a variety of
      organic substrates [figure: see text] by hydrogen peroxide as the oxygen source.
      The perhydrates I, formed in situ by the addition of hydrogen peroxide to the
      alpha-halo ketones, are quite strong electrophilic oxidants and expectedly
      transfer an oxygen atom to diverse nucleophilic acceptors. Thus, alpha-halo
      ketones have been successfully employed for catalytic epoxidation, heteroatom (S,
      N) oxidation, and arene oxidation. Although high diastereoselectivities have been
      achieved by these nonmetal catalysts, no enantioselective epoxidation and
      sulfoxidation have so far been reported. Consequently, it is anticipated that
      catalytic oxidations by perhydrates hold promise for further development,
      especially, and should ways be found to transfer the oxygen atom
      enantioselectively. The second class, namely, the dioxiranes, has been
      extensively used during the last two decades as a convenient oxidant in organic
      synthesis. These powerful and versatile oxidizing agents are readily available
      from the appropriate ketones by their treatment [figure: see text] with potassium
      monoperoxysulfate. The oxidations may be performed either under stoichiometric or
      catalytic conditions; the latter mode of operation is featured in this review. In
      this case, a variety of structurally diverse ketones have been shown to catalyze
      the dioxirane-mediated epoxidation of alkenes by monoperoxysulfate as the oxygen
      source. By employing chiral ketones, highly enantioselective (up to 99% ee)
      epoxidations have been developed, of which the sugar-based ketones are so far the
      most effective. Reports on catalytic oxidations by dioxiranes other than
      epoxidations are scarce; nevertheless, fructose-derived ketones have been
      successfully employed as catalysts for the enantioselective CH oxidation in vic
      diols to afford the corresponding optically active alpha-hydroxy ketones. To
      date, no catalytic asymmetric sulfoxidations by dioxiranes appear to have been
      documented in the literature, an area of catalytic dioxirane chemistry that
      merits attention. A third class is the imines; their reaction with hydrogen
      peroxide or monoperoxysulfate affords oxaziridines. These relatively weak
      electrophilic oxidants only manage to oxidize electron-rich substrates such as
      enolates, silyl enol ethers, sulfides, selenides, and amines; however, the
      epoxidation of alkenes has been achieved with activated oxaziridines produced
      from perfluorinated imines. Most of the oxidations by in-situ-generated
      oxaziridines have been performed stoichiometrically, with the exception of
      sulfoxidations. When chiral imines are used as catalysts, optically active
      sulfoxides are obtained in good ee values, a catalytic asymmetric oxidation by
      oxaziridines that merits further exploration. The fourth class is made up by the
      iminium ions, which with monoperoxysulfate lead to the corresponding
      oxaziridinium ions, structurally similar to the above oxaziridine oxidants except
      they possess a much more strongly electrophilic oxygen atom due to the positively
      charged ammonium functionality. Thus, oxaziridinium ions effectively execute
      besides sulfoxidation and amine oxidation the epoxidation of alkenes under
      catalytic conditions. As expected, chiral iminium salts catalyze asymmetric
      epoxidations; however, only moderate enantioselectivities have been obtained so
      far. Although asymmetric sulfoxidation has been achieved by using stoichiometric
      amounts of isolated optically active oxaziridinium salts, iminium-ion-catalyzed
      asymmetric sulf-oxidations have not been reported to date, which offers
      attractive opportunities for further work. The fifth and final class of nonmetal
      catalysts concerns the stable nitroxyl-radical derivatives such as TEMPO, which
      react with the common oxidizing agents (sodium hypochlorite, monoperoxysulfate,
      peracids) to generate oxoammonium ions. The latter are strong oxidants that
      chemoselectively and efficiently perform the CH oxidation in alcohols to produce
      carbonyl compounds rather than engage in the transfer of their oxygen atom to the
      substrate. Consequently, oxoammonium ions behave quite distinctly compared to the
      previous four classes of oxidants in that their catalytic activity entails
      formally a dehydrogenation, one of the few effective nonmetal-based catalytic
      transformations of alcohols to carbonyl products. Since less than 1 mol% of
      nitroxyl radical is required to catalyze the alcohol oxidation by the inexpensive
      sodium hypochlorite as primary oxidant under mild reaction conditions, this
      catalytic process holds much promise for future practical applications.

PMID- 11840993
TI  - Anellated heterophospholes and phospholides and analogies with related non
      phosphorus systems.

PMID- 11840994
TI  - U.S. markets for dental implants 2001: executive summary.

PMID- 11840995
TI  - Proceedings of a symposium on the treatment of psychoses in older people.
      Barcelona, November 2000.

PMID- 11840996
TI  - Absence of mycoplasma contamination in the anthrax vaccine.

PMID- 11840997
TI  - [German Pain Conference. 3-7 October 2001, Berlin. Abstracts].

PMID- 11840998
TI  - The relationship between pharmacists' tenure in community setting and moral
      reasoning.
AB  - OBJECTIVE: To explore the relationship between pharmacists' tenure in the
      community setting and their moral reasoning abilities. DESIGN: Systematic random
      sample design. SETTING: A large southeastern city in the United States.
      PARTICIPANTS: 450 independent and chain community pharmacists identified from the
      state board of pharmacy list of licensed community pharmacists. INTERVENTIONS: A
      mailed questionnaire that included a well-known moral reasoning instrument and
      collected demographic information. MAIN OUTCOME MEASURES: Moral Reasoning
      abilities and tenure of community pharmacists. RESULTS: As a group, community
      pharmacists with greater years of tenure in community practice scored
      significantly lower on moral reasoning than those pharmacists with fewer years of
      tenure (p=0.016). CONCLUSION: Four plausible explanations for the results are
      given including: a) a selection of lower ethical reasoners and/or an exodus of
      higher ethical reasoners from the community setting; b) a retrogression in the
      moral reasoning skills as community pharmacists obtain tenure in this setting; c)
      differences between the low and high moral reasoning groups may be due to a
      cohort effect; and d) the obtained practitioner sample may not have been
      representative of the population of community pharmacists.

PMID- 11840999
TI  - Cancer prevention: molecular mechanisms to clinical applications. Proceedings of
      a conference. New York City, New York, USA. November 10-11, 2000.

PMID- 11841001
TI  - Proceedings and abstracts of the 3rd International Symposium on Stallion
      Reproduction. January 10-12, 2001. Fort Collins, Colorado, USA.

PMID- 11841000
TI  - Meeting industry challenges.

PMID- 11841002
TI  - Title tattles.

PMID- 11841003
TI  - Title tattles.

PMID- 11841004
TI  - Research of the Holiday kind. Celestial determinants of success in research.

PMID- 11841005
TI  - Research of the Holiday kind. Case report: microcardia secondary to chronic
      adrenocortical insufficiency.

PMID- 11841006
TI  - Research of the Holiday kind. The PATE trial: prevention of appendicitis using
      Trident exclusively.

PMID- 11841007
TI  - Research of the Holiday kind. Ants.

PMID- 11841008
TI  - Research of the Holiday kind. Shake, rattle and roil.

PMID- 11841009
TI  - The well-made bed: an unappreciated public health risk.

PMID- 11841010
TI  - Canadians out of bounds. Rapid needs assessment.

PMID- 11841011
TI  - Canadians out of bounds. The 55th patient.

PMID- 11841012
TI  - Canadians out of bounds. Hold the soup!

PMID- 11841013
TI  - Canadians out of bounds. Sooner or later, everyone is going to die anyway.

PMID- 11841014
TI  - Diversions. Grand rounds: osteodensosis.

PMID- 11841016
TI  - Diversions. To whom it may concern.

PMID- 11841015
TI  - Diversions. There was a young surgeon who swallowed a flea.

PMID- 11841017
TI  - Diversions. Motel New Hampshire.

PMID- 11841018
TI  - New York, Sept. 11, 2001.

PMID- 11841019
TI  - Newfoundland, Sept. 11, 2001.

PMID- 11841020
TI  - Sky doc.

PMID- 11841021
TI  - The medical Cervantes.

PMID- 11841022
TI  - Spittoon Christmas.

PMID- 11841023
TI  - Diversions. The xerotic nephrologist.

PMID- 11841024
TI  - CMAJ, 90 years ago.

PMID- 11841025
TI  - CMAJ turns 90. September examinations, 1910.

PMID- 11841026
TI  - Proceedings of the 26th Annual ISCE Conference: Research and Technology Transfer
      in Computerized Electrocardiology. April 21-26, 2001. Stuart, Florida.

PMID- 11841027
TI  - Mysteries of life: Is there "something else"?

PMID- 11841028
TI  - Ethical issues in biomedical publishing.

PMID- 11841029
TI  - The scientist demanding wisdom: the "Bridge to the Future" by Van Rensselaer
      Potter.

PMID- 11841030
TI  - 1999 Membership directory.

PMID- 11841031
TI  - Preconception gender selection.
AB  - Safe and effective methods of preconception gender selection through flow
      cytometric separation of X- and Y-bearing sperm could greatly increase the use of
      gender selection by couples contemplating reproduction. Such a development raises
      ethical, legal, and social issues about the impact of such practices on
      offspring, on sex ratio imbalances, and on sexism and the status of women. This
      paper analyzes the competing interests in preconception gender selection, and
      concludes that its use to increase gender variety in a family, and possible for
      selecting the gender of firstborn, might in many instances be ethically
      acceptable.

PMID- 11841032
TI  - Proceedings of the 1st Beaune Seminar in Transplantation Research. Beaune,
      France, 7-8 June 2001.

PMID- 11841034
TI  - Widespread microdysgenesis in therapy-resistant epilepsy--a case report on post
      mortem findings.
AB  - Microdysgenesis is a subtle malformation, which is often found in specimens from
      epilepsy surgery. It is, however, not clear whether the changes are focal or
      diffuse. A recent autopsy case offered an opportunity to investigate whether
      microdysgenesis found after temporal lobe surgery was focal or widespread in the
      brain. The entire brain of a 20-year-old patient who died suddenly and
      unexpectedly was examined histologically. Microdysgenesis had previously been
      diagnosed after a left temporal lobectomy performed because of therapy-resistant
      seizures. A light microscopic examination was performed on specimens stained with
      Luxol-fast blue-cresyl violet and polyclonal antibodies to glial fibrillary
      acidic protein. Widespread microdysgenesis with irregular nerve cell distribution
      in the cortex and an increased number of nerve cells in cortical layer I and in
      the white matter was found in the right temporal and parietal lobes and
      bilaterally in the frontal and occipital lobes. The post-mortem examination
      confirmed the previous diagnosis of microdysgenesis and showed that the changes
      were widespread in a patient who was operated on because of focal epilepsy.

PMID- 11841033
TI  - Caspase-3 activation and caspase-like proteolytic activity in human perinatal
      hypoxic-ischemic brain injury.
AB  - Human perinatal hypoxic-ischemic brain injury is an important cause of death and
      morbidity. One relatively common pattern of perinatal injury involves selective
      neuronal death in the ventral gray matter of the pons and in the subiculum of the
      hippocampal formation, classically termed 'pontosubicular neuronal necrosis'
      (PSN). The vulnerable neurons undergo karyorrhectic condensation of their nuclear
      chromatin and exhibit in situ end labeling for DNA fragmentation, leading to the
      recent reclassification of cell death in PSN as apoptotic. Caspase activation
      plays a central role in apoptosis and caspase-3 appears to be an especially
      important effector enzyme in neuronal apoptosis. In this study we performed
      immunohistochemistry on brain sections from six postmortem cases of PSN using two
      polyclonal antisera; CM1, a specific marker of caspase-3 activation, and fractin,
      which specifically recognizes a neoepitope at a caspase cleavage site in actin,
      and is therefore a marker of caspase-like proteolytic activity. Numerous CM1- and
      fractin-immunolabeled neurons were seen in the nuclei pontis and subiculum in
      each case, and the great majority showed karyorrhectic morphology. The
      immunostaining involved the nuclei and cytoplasm of these cells and the proximal
      portions at least of their neuritic processes. Some neurons exhibited a more
      extensive pattern of dendritic fractin labeling. Frequent CM1- and fractin
      immunoreactive axonal segments were also seen. The identification of caspase-3
      activation and caspase-like proteolytic activity in PSN cases in this study
      suggests that caspase inhibitors may potentially have a therapeutic
      neuroprotective role in human perinatal hypoxic-ischemic brain injury.

PMID- 11841035
TI  - Healthcare task force cut. But Justice Department still watching for antitrust.

PMID- 11841037
TI  - Preparing for battle. HCA whistleblowers bring in big guns for trial.

PMID- 11841036
TI  - N.J. law allows docs to bargain.

PMID- 11841038
TI  - [The cause of the incontinence was solved by laparotomy].

PMID- 11841039
TI  - Development of a Vietnamese version of the Short form-36 Health Survey.
AB  - We aimed to test the psychometric properties of a culturally relevant translation
      of the medical outcomes study short form-36 health survey (SF-36) with
      prospective Vietnamese migrants. The translated survey was interviewer
      administered to 1610 Vietnamese aged over 15 years who had applied to migrate to
      Australia. All but two SF-36 items had good discriminant validity, and all eight
      scales of the Vietnamese version of the SFS-36 had good discriminant validity,
      which supports the use of SF-36 constructs to assess self-reported health status
      among Vietnamese migrants. However, the mental health, vitality and bodily pain
      scales demonstrated low internal consistency. This finding is likely to be a
      product of the increased diversity among scale items following modifications to
      improve cultural relevance. Further modifications to improve the internal
      consistency of these scales are required.

PMID- 11841040
TI  - Mechanisms of reduced human vascular cell migration after photodynamic therapy.
AB  - Restenosis results from intimal hyperplasia and constrictive remodeling following
      cardiovascular interventions. Photodynamic therapy (PDT) has been shown to
      inhibit intimal hyperplasia in vivo by preventing neointimal repopulation of the
      treated vessel. This study was undertaken in an attempt to further dissect the
      mechanisms by which PDT acts on secreted and extracellular matrix proteins to
      inhibit migration of cultured human vascular cells. PDT of three-dimensional
      collagen gels inhibited invasive human smooth muscle cell (SMC) migration,
      whereas cell-derived matrix metalloproteinase production remained unaltered.
      Additionally, PDT generated cross-links in the collagen gels, a result
      substantiated in an ex vivo model whereby PDT rendered the treated vessels
      resistant to pepsin digestion and inhibited invasive migration of SMC and
      fibroblasts. These data support the premise that by inducing matrix protein cross
      links, rendering the vessel resistant to degradation, in vivo PDT inhibits
      repopulation of the vessel and therefore intimal hyperplasia.

PMID- 11841041
TI  - Effects of surfactants on the photosensitized production of tyrosine radicals
      studied by photo-CIDNP.
AB  - The influence of the surfactants sodium dodecyl sulphate, cetyltrimethyl-ammonium
      bromide and triton X-100 on the photochemically induced dynamic nuclear
      polarization (CIDNP) of N-acetyl tyrosine has been investigated. Three
      photosensitizers were used to generate polarization: thionin, eosin Y and flavin
      mononucleotide. 600 MHz 1H photo-CIDNP experiments, supported by laser flash
      photolysis transient absorption measurements, indicate that the neutral triton
      surfactant has no influence on the nuclear polarization, but that the other two,
      charged, amphiphiles affect the photochemistry in a variety of ways, depending on
      the surfactant concentration and the identity of the sensitizer.

PMID- 11841042
TI  - The opposed effect of 5-azacytidine and light on the development of reproductive
      structures in Neurospora crassa.
AB  - Blue light inhibits the formation of asexual cycle spores (conidia) and
      stimulates the development of the sexual (female) reproductive structures
      (protoperithecia) in the nitrogen-starved mycelium of Neurospora crassa. The DNA
      methylation inhibitor, 5-azacytidine (3-300 microM), opposed the effect of light
      by suppressing the protoperithecia formation and stimulating a conidiation. The
      addition of 300 microM 5-azacytidine inhibited protoperithecia formation in the
      dark-cultivated mycelium by about two orders of magnitude and activated
      conidiation in the light-exposed mycelium by almost three orders of magnitude.
      Both in the dark-cultivated and the irradiated mycelium treated with various 5
      azacytidine concentrations, the yield of conidia and protoperithecia demonstrated
      an inverse relationship. We suggest that DNA methylation and blue light are
      involved in the organism's selection of sexual or asexual reproductive cycle.

PMID- 11841044
TI  - Application of resampling techniques to estimate exact significance levels for
      covariate selection during nonlinear mixed effects model building: some
      inferences.
AB  - PURPOSE: One of the main objectives of the nonlinear mixed effects modeling is to
      provide rational individualized dosing strategies by explaining the
      interindividual variability using intrinsic and/or extrinsic factors
      (covariates). The aim of the current study was to evaluate, using computer
      simulations and real data, methods for estimating the exact significance level
      for including or excluding a covariate during model building. METHODS: Original
      data were simulated using a simple one-compartment pharmacokinetic model with
      (full model) or without (null model) covariates (one or two). The covariate
      values in the original data were resampled (using either permutations or
      parametric bootstrap methods) to generate data under the null hypothesis that
      there is no covariate effect. The original and permuted data were fitted to null
      and full models, using first-order and first-order condition estimation (with or
      without interaction) methods in NONMEM, to compare the asymptotic and conditional
      p-value. Target log-likelihood ratio cutoffs for assessing covariate effects were
      derived. RESULTS: The simulations showed that for sparse as well as dense data,
      the first-order condition estimation methods yielded the best results while the
      first-order method performs somewhat better for sparse data. Depending on the
      modeling objective, the appropriate asymptotic p-value can be substituted for the
      conditional significance level. Target log-likelihood ratio cutoffs should be
      determined separately for each covariate when exact p-values are important.
      CONCLUSIONS: Resampling methods can be employed to estimate the exact
      significance level for including a covariate during nonlinear mixed effects model
      building. Some reasonable inferences can be drawn for potential application to
      design future population analyses.

PMID- 11841043
TI  - The antiviral protein human lactoferrin is distributed in the body to
      cytomegalovirus (CMV) infection-prone cells and tissues.
AB  - PURPOSE: Lactoferrin has anti-Cytomegalovirus (CMV) and -HIV properties in vitro.
      However, the pharmacokinetic behavior of the 80-kD protein has not been well
      defined. We, therefore, assessed the plasma decay and body distribution of
      lactoferrin after intravenous administration to freely moving rats. Furthermore,
      the systemic availability of lactoferrin after intraperitoneal dosing was
      determined. METHODS AND RESULTS: After intravenous injection, human lactoferrin
      (hLF) was rapidly cleared from the plasma, but higher doses resulted in prolonged
      plasma levels. Immunohistochemical analysis revealed a pronounced distribution of
      hLF to endothelial cells in the liver whereas diffuse staining in hepatocytes
      indicated the presence of considerable amounts in this large cell population.
      This endothelial association, which also was found in other organ/tissues,
      including blood vessels. was confirmed by in vitro cell-binding studies. In
      addition, leukocytes in plasma that were infiltrated in various organs showed
      binding of hLF. A small fraction of hLF was transported into the lymphatic
      system. Western blot analysis revealed that hLF, present in the various organs.
      mainly consisted of an 80-kD protein. After intraperitoneal administration, small
      amounts of 80-kD hLF distributed to the general circulation. The bioavailability
      was 0.6% but increased to 3.6% after multiple administrations. CONCLUSIONS: The
      affinity of hLF for endothelial cells and leukocytes, and its penetration into
      the lymphatic system, indicates that this protein reaches target cells and body
      compartments that are crucial for CMV and HIV replication. The ability to reach
      the blood compartment after intraperitoneal dosing offers opportunities for
      parenteral administration of the protein in future studies on its antiviral
      effects in vivo.

PMID- 11841045
TI  - In search of health parity: an opportunity or another disparity?

PMID- 11841047
TI  - Australian Dental Research Foundation research grant abstracts.

PMID- 11841046
TI  - Guidelines for the use of parenteral and enteral nutrition in adult and pediatric
      patients.

PMID- 11841048
TI  - Autochthonous mucosal leishmaniasis in a hemodialyzed Italian patient.
AB  - A case of mucosal leishmaniasis in a 60-year old hemodialysis patient who had
      never lived outside Italy is described. The patient complained of fever,
      epistaxis and nasal obstruction. An anterior rhinoscopy disclosed a mass of two
      centimetres in diameter in the right nasal fossa. Histological examination
      revealed Leishmania amastigotes. Serology for Leishmania was positive with
      antibody titer of 1/320. A culture yielded a very slow growth of Leishmania
      infantum MON-24. In spite of a two-month treatment with oral itraconazole, the
      lesions progressively worsened. Treatment with topical paromomycin sulfate
      determined the complete resolution of the lesions within four months, with a
      residual perforation of the septum. This case demonstrates that localization of
      Leishmania spp must be considered in the differential diagnosis of mucosal
      lesions in hemodialyzed patients, even in countries not at risk for this
      parasite. Moreover, this case indicates the important role of the immune system
      in the evolution of the disease.

PMID- 11841049
TI  - Ralstonia pickettii bacteraemia in a cord blood transplant recipient.
AB  - A seven-year old boy with acute lymphoblastic leukemia underwent an HLA
      mismatched cord blood transplant. He developed grade 2 mucositis requiring
      morphine infusion and grade 3-4 hyperacute graft-versus-host disease affecting
      the skin, gastrointestinal tract, and liver requiring pulse methylprednisolone.
      On days 21, 23, and 24 post-transplant, blood culture obtained through the
      central line and periphery were positive for Ralstonia pickettii. The same strain
      (with the same biochemical profile and antibiotic susceptibility pattern) was
      also recovered from surveillance throat swab cultures from day 11 to day 24 and
      surveillance rectal swab cultures from day 16 to day 24. The patient responded to
      intravenous cefoperazone/sulbactam and ciprofloxacin and blood culture became
      negative 3 days after commencement of the antibiotics. Although R. pickettii is
      of low virulence and is a frequent contaminant of blood cultures, it should not
      be overlooked when it is repeatedly recovered from sterile body fluids,
      especially in immunocompromised hosts.

PMID- 11841050
TI  - Effects of silymarin MZ-80 on oxidative stress in patients with alcoholic
      cirrhosis. Results of a randomized, double-blind, placebo-controlled clinical
      study.
AB  - BACKGROUND: The role of silymarin in the treatment of liver cirrhosis is
      controversial. AIM: Clinical outcome,biochemical profile and the antiperoxidative
      effects of silymarin MZ-80 during 6 months treatment were investigated in
      patients with alcoholic liver cirrhosis. METHODS: Sixty consecutive patients with
      alcoholic liver cirrhosis were randomized to receive either silymarin MZ-80 (S)
      (150 mg t.i.d. per day) or placebo (P) for periods of 6 months. Erythrocyte total
      glutathione (GSH) content, platelet malondialdehyde (MDA) and serum amino
      terminal propeptide of procollagen Type III (PIIINP) were determined at baseline
      and at the end of treatment. RESULTS: Forty-nine patients completed the study (24
      S and 25 P). The 2 groups were well-matched for demographic as well as baseline
      clinical and laboratory parameters. Silymarin increased total GSH at 6 months
      (4.5 +/- 3.4 to 5.8 +/- 4.0 micromol/g Hb) whereas, in the placebo group, GSH
      remained unchanged (4.1 +/- 3.9 to 4.4 +/- 4.1 micromol/gHb) (p < 0.001), and
      platelet-derived non-induced MDA decreased by 33% (p < 0.015). A parallel
      decrease in PIIINP values was seen with silymarin (1.82 1.03 to 1.36 +/- 0.5
      U/ml, p < 0.033) but not with placebo (1.31 +/- 0.4 to 1.27 +/- 0.6 U/ml). There
      were no concurrent changes on laboratory indices of the pathology. CONCLUSIONS:
      Silymarin is well-tolerated and produces a small increase in glutathione and a
      decrease in lipid peroxidation in peripheral blood cells in patients with
      alcoholic liver cirrhosis. Despite these effects no changes in routine liver
      tests were observed during the course of therapy.

PMID- 11841051
TI  - Multilayer Gafchromic film detectors for breast skin dose determination in vivo.
AB  - Assessment of skin dose delivered to patients from radiotherapy x-ray beams
      should be performed both inside and outside the prescribed treatment fields. A
      multilayer Gafchromic film detector which has high sensitivity for detection of
      radiation can be used to measure skin dose in a two-dimensional map over the skin
      surface if required. This is an advantage over other detectors, which only
      provide point dose estimates. A study of 25 patients undergoing breast
      irradiation was performed to analyse the ability of the multilayer detector to
      analyse skin dose and to assess both in-field and out-of-field radiation doses
      delivered during tangent field breast irradiation. Results show that the main
      contributor to total skin dose within the treatment field was delivered by exit
      dose. However, outside the field, most dose was delivered by entry beams.
      Patients with smaller breast separations where found, in general, to receive a
      higher total skin dose from entry and exiting beams at the central axis. Results
      also showed that a significant skin dose was delivered outside the treatment
      field and the main cause of this dose was from electron contamination from entry
      beams. The multilayer Gafchromic film detector provided adequate skin dose
      assessment within one fraction of treatment for in vivo results.

PMID- 11841052
TI  - An algorithm for the optimum combination of data from arbitrary magnetic
      resonance phased array probes.
AB  - When summing the spectra acquired with phased array coils, signals with low
      signal-to-noise ratio or wrongly corrected phase may degrade the overall signal
      to-noise ratio (SNR). Here we present a mathematical expression predicting the
      dependence of combined SNR on the signal-to-noise ratios and errors in phase
      correction of composite signals. Based on this equation, signals that do not lead
      to an overall increase in signal-to-noise ratio can be identified and excluded
      from the weighted sum of signals. This tool is particularly useful for the
      combination of large numbers of signals. Additionally, a simple and robust
      algorithm for calculating the complex weighting factors necessary for the signal
      to-noise weighted combination of spectroscopic data is presented. Errors in the
      calculation and correction of relative phase differences between composite
      spectra are analysed. The errors have a negligible effect on the overall spectral
      SNR for typical clinical magnetic resonance spectroscopy (MRS). The signal
      combination routine developed here has been applied to the first in vivo MRS
      study of human rectal adenocarcinomas at 1.5 T (Dzik-Jurasz A S K, Murphy P S,
      George M, Prock T, Collins D J, Swift I and Leach M O 2001 Magn. Reson. Med. at
      press), showing improvements of combined spectral SNR of up to 34% over the
      maximum SNR from a single element.

PMID- 11841053
TI  - The three-dimensional effects of orthodontic treatment on the facial soft tissues
      -a preliminary study.
AB  - OBJECTIVE: To examine the three-dimensional effects of extraction and non
      extraction orthodontic treatment on the facial soft tissues. SETTING: Department
      of Orthodontics, Royal London Hospital. DESIGN: Longitudinal study of two
      prospective cohorts of patients who were attending for orthodontic treatment.
      METHOD 12 patients were included in each group, in accordance with the selection
      criteria. Three-dimensional optical surface scans of these patients were obtained
      in the one month prior to having fixed appliances placed and this was repeated at
      the end of treatment. RESULTS: The average face of the non-extraction patients
      was of greater general dimensions than the extraction average, both at the start
      and the end of treatment. During the fixed appliance treatment, the vermilion of
      the upper lip became more protrusive to a similar extent in both groups in
      relation to the reference plane. The lower lip vermilion and the philtrum showed
      no change for either group over the treatment time. The labiomental fold area
      showed a slightly greater forward movement in the extraction group with
      treatment. CONCLUSION: Three-dimensional optical surface scanning allows data
      from the whole of the face to be assessed, as opposed to the lateral profile view
      used in the majority of the studies to date. The effects of the two types of
      treatment on the facial soft tissues were very similar, indicating that
      orthodontic treatment involving the extraction of teeth does not have a
      detrimental effect on the face.

PMID- 11841054
TI  - Removable appliances.

PMID- 11841055
TI  - Good occlusal practice in the provision of implant borne prostheses.
AB  - The increased use of endosseous dental implants means that many dentists will
      encounter patients with dental implants in their everyday practice. Dental
      practitioners might be actively involved in the provision of implant borne
      prostheses at both the surgical and restorative phases, or only at the
      restorative stage. This section is written for all dentists and aims to examine
      the subject of occlusion within implantology. It aims to provide guidelines of
      good occlusal practice to be used in the design of the prosthesis that is
      supported or retained by one or more implants. As implantology is a 'new'
      discipline of dentistry, there are fewer standard texts and this section,
      therefore, is much more extensively referenced than the subjects that have been
      considered to date.

PMID- 11841056
TI  - Influence of load distribution and recycle rate in step-fed facultative ponds.
AB  - This study presents the results of research on a wastewater treatment system with
      four identical facultative ponds in series with step-feeding and recirculation
      (SFFPR). Four modes of distribution of the influent were studied, which were (in
      percentages of the inflow per pond): C1 = 25/25/25/25; C2 = 50/20/20/10; C3 =
      50/50/0/0; C4 = 100/0/0/0. The organic loading applied to the four ponds overall
      was around 200 kg BOD5/ha.d. The distribution C4 = 100/0/0/0 was selected for
      studying the recycle rate. Three recycling rates were studied: 0.5Q, 1Q and 2Q.
      COD and BOD5 removal efficiencies were high whatever the step-feed distribution.
      For the distribution C1 and C2, the four ponds were homogeneous. The equal
      distribution of organic loading rate in C2 distribution was most beneficial for
      algal growth. For piston pattern distributions (C3 and C4), the ponds receiving
      the highest loading showed a bacterial biomass higher than that of the primary
      production. Increasing the recirculation rate seemed to lead towards
      homogenisation of the ponds, while a decrease appeared to lead to their
      individualisation and increased their productivity. The SFFPR constitutes a stage
      of the treatment process which can replace the facultative stage; it produces a
      high effluent quality and decreases land area requirements.

PMID- 11841057
TI  - Performance of a baffled facultative pond treating piggery wastes.
AB  - This paper shows the performance of a baffled facultative pond for the treatment
      of piggery wastes. The full-scale system is composed of an equalizer, one
      decanter (DP), two anaerobic ponds (LA1 and LA2), one facultative pond (LF), with
      five baffles, and one maturation pond with water hyacinths (LAG). The studies
      were conducted over a 12 month period in the west region of Santa Catarina,
      Brazil. The system was supplied daily with a volume of 3 m3/day of farm wastes. A
      good performance of the treatment system was obtained with average removal
      efficiencies of 98% for chemical oxygen demand, 93% for total solids, 98% for
      total phosphorus, 92% for total nitrogen, 7 log units of faecal coliforms and 5
      log units of total coliforms. The facultative pond performed well, removing 43%
      of the chemical oxygen demand, 47% of total nitrogen and 54% of total phosphorus.
      It was found that the first baffle in the facultative pond was mainly responsible
      for the efficiency of this pond, and compared with another study the introduction
      of the baffles improved the removal efficiency by 20% for total phosphorus.

PMID- 11841058
TI  - Treatment of piggery wastes in waste stabilization ponds.
AB  - The piggery industry produces high effluent loads. This is due to the high
      concentration of animals kept in a confined space, foods with high protein
      content that are not well assimilated by the animals, and poor on-farm water
      management. In this study, we present the characteristics, design, site
      selection, soil study, and the construction of a pilot pond system for a family
      farm located in a warm climate area. The design includes a solids sedimentation
      phase, an anaerobic pond, a facultative pond and three maturation ponds. Once the
      system had reached steady state, the organic and bacterial kinetic constants were
      determined for each pond. The control parameters were determined and the
      dissolved oxygen and removal efficiency profiles were obtained. The results
      indicate that the effluent from the second maturation pond complies with the
      Official Mexican Standard for reuse in agriculture ("1000 FC/100 ml).

PMID- 11841059
TI  - Process performance assessment of algae-based and duckweed-based wastewater
      treatment systems.
AB  - A pilot plant experiment was carried out to assess differences in environmental
      conditions and treatment performance in two systems for wastewater treatment:
      algae-based ponds (ABP) and duckweed-based (Lemna gibba) ponds (DBP). Each system
      consisted of a sequence of 4 equal ponds in series and was fed with a constant
      flow rate of partially treated wastewater from Birzeit University. Physico
      chemical parameters and the removal of organic matter, nutrients and faecal
      coliforms were monitored within each treatment system over a period of 12 months.
      The results show clear differences in the environmental conditions. In ABP
      significantly (P>0.05) higher pH and DO values were observed than in DBP. DBP
      were more efficient in removal of organic matter (BOD and TSS) than ABP. The
      faecal coliform reduction was higher in ABP. However, the quality of the effluent
      from the third and fourth duckweed pond (total retention time of 21 and 28 days)
      did not exceed the WHO-criteria for unrestricted irrigation during both the
      summer and winter period, respectively. During the summer period, the average
      total nitrogen was reduced more in ABP (80%) than in DBP (55%). Lower values were
      measured during the winter period. Seasonal nitrogen reductions of the two
      systems were significantly different (P>0.05). In DBP, 33% and 15% of the total
      nitrogen was recovered into plant biomass and removed from the system via
      duckweed harvesting during the summer and winter period, respectively. This study
      showed that there were differences in the environmental conditions and treatment
      efficiencies between the two systems.

PMID- 11841060
TI  - Optimization of a monitoring network for sulfur dioxide.
AB  - In this study, we develop and apply a methodology to reduce an existing
      monitoring network to find an optimal configuration of a smaller network. We use
      a criterion based on locally weighted regression with two different weight
      functions. The methodology is applied to the Dutch national SO2 network and
      offers the possibility to include different politically relevant options in the
      model by weight criteria. Because full enumeration of all monitoring networks is
      impossible, a combinatorial search algorithm is applied to find a (sub)optimal
      solution. If different (optimal) monitoring networks result from different
      criteria, then the best can be selected.

PMID- 11841061
TI  - Soil solid-phase controls lead activity in soil solution.
AB  - Lead pollution of the environment is synonymous with civilization. It has no
      known biological function, and is naturally present in soil, but its presence in
      food crops is deemed undesirable. The concern regarding Pb is mostly due to
      chronic human and animal health effects, rather then phytotoxicity. However, not
      much is known about the chemistry and speciation of Pb in soils. We determined
      the activity of Pb2+, in near neutral and alkaline soils, representative of
      alluvial, desertic and calcareous soils of Egypt, using the competitive chelation
      method. Lead activity ranged from 10(-6.73) to 10(-4.83) M, and was negatively
      correlated with soil and soil solution pH (R2 = -0.92, P < 0.01 and R2 = -0.89, P
      < 0.01, respectively). It could be predicted in soil solution from the equation:
      log(Pb2+) = 9.9 - 2pH. A solubility diagram for the various Pb minerals found in
      soil was constructed using published thermodynamic data obtained from the
      literature, and our measured Pb2+ activities compared with this information. The
      measured Pb2+ activities were undersaturated with regard to the solubility of
      PbSiO3 in equilibrium with SiO2 (soil). However, they were supersaturated with
      regard to the solubilities of the Pb carbonate minerals PbCO3 (cerussite) and
      Pb3(CO3)2(OH)2 in equilibrium with atmospheric CO2 and hydroxide Pb(OH)2. They
      were also supersaturated with regard to the solubilities of the Pb phosphate
      minerals Pb3(PO4)2, Pb5(PO4)3OH, and Pb4O(PO4)2 in equilibrium with tricalcium
      phosphate and CaCO3. The activity of Pb2+ was not regulated by any mineral of
      known solubility in our soils, but possibly by a mixture of Pb carbonate and
      phosphate minerals.

PMID- 11841062
TI  - Adsorption of cadmium, copper, nickel, and zinc to a poly(tetrafluorethene)
      porous soil solution sampler.
AB  - Suction cups made of poly(tetrafluorethene) (PTFE) are widely used for sampling
      of soil solution. A brand (Prenart) of PTFE cups was tested for adsorption of Cd,
      Cu, Ni, and Zn at low concentrations under different conditions. In a laboratory
      experiment adsorption from a 10 microg L(-1) heavy metal solution with a 0.01 M
      NaCl background electrolyte was investigated at pH 3.6, 4.5, and 5.8 by pumping
      the solutions through the cups. The effect of three different ionic compositions
      was also investigated using 0.01 M CaCl2, 0.01 M NaCl, and no background
      electrolyte at pH 4.5. In 0.01 M NaCl electrolyte at pH 5.8 the cups acted as
      effective filters. At pH 3.6 after 300 mL of solution had passed through the cup,
      equivalence between the Cd and Ni concentrations in influent and effluent was
      found. No equivalence between effluent and influent concentrations was found for
      Zn and Cu at pH 4.5 and 5.8. With Ca as the electrolyte, no adsorption of Cd, Ni,
      or Zn was found. In Na electrolyte, equivalence between influent and effluent
      concentrations for Cd, Ni, and Zn was reached. The difference between effluent
      and influent concentrations of Zn, Ni, and Cd remained significant in the absence
      of electrolyte. For all pH values and electrolytes the difference between
      effluent and influent concentrations of Cu was significant. It is concluded that
      PTFE cups affect the concentrations of heavy metals sampled at low soil solution
      concentrations. Cadmium, Cu, Ni, and Zn adsorb to the cup at pH > 4.5 and low
      ionic strength.

PMID- 11841063
TI  - Runoff and drainage losses of atrazine, metribuzin, and metolachlor in three
      water management systems.
AB  - Rainfall can transport herbicides from agricultural land to surface waters, where
      they become an environmental concern. Tile drainage can benefit crop production
      by removing excess soil water but tile drainage may also aggravate herbicide and
      nutrient movement into surface waters. Water management of tile drains after
      planting may reduce tile drainage and thereby reduce herbicide losses to surface
      water. To test this hypothesis we calculated the loss of three herbicides from a
      field with three water management systems: free drainage (D), controlled drainage
      (CD), and controlled drainage with subsurface irrigation (CDS). The effect of
      water management systems on the dissipation of atrazine (6-chloro-N2-ethyl-N4
      isopropyl-1,3,5-triazine-2,4-diamine), metribuzin [4-amino-6-(1,1-dimethylethyl)
      3-(methylthio)-1,2,4-triazine-5(4H)-one), and metolachlor [2-chloro-N-(2-ethyl-6
      methylphenyl)-N-(2-methoxy-1-methylethyl)acetamide] in soil was also monitored.
      Less herbicide was lost by surface runoff from the D and CD treatments than from
      CDS. The CDS treatment increased surface runoff, which transported more herbicide
      than that from D or CD treatments. In one year, the time for metribuzin residue
      to dissipate to half its initial value was shorter for CDS (33 d) than for D (43
      d) and CD (46 d). The half-life of atrazine and metolachlor were not affected by
      water management. Controlled drainage with subsurface irrigation may increase
      herbicide loss through increased surface runoff when excessive rain is received
      soon after herbicide application. However, increasing soil water content in CDS
      may decrease herbicide persistence, resulting in less residual herbicide
      available for aqueous transport.

PMID- 11841064
TI  - Web-based CBT for selective mutism.

PMID- 11841065
TI  - Assessment of activities of daily living with an ambulatory monitoring system: a
      comparative study in patients with chronic low back pain and nonsymptomatic
      controls.
AB  - OBJECTIVE: The aim of this study was twofold: (1) to investigate whether
      differences in activities of daily living exist between patients with chronic low
      back pain (CLBP) and nonsymptomatic controls; (2) to investigate the day-to-day
      variability in daily activities. DESIGN: Physical activities were measured over a
      24-hour period with an ambulant monitoring system. SETTING: Measurements were
      carried out in the subject's own environment. SUBJECTS: Forty-seven CLBP patients
      and 10 nonsymptomatic controls participated in this study. RESULTS: On group
      level, CLBP patients show a lower activity pattern compared with controls,
      especially during the evening. This is reflected in a lower walking step
      frequency during the day and evening, more lying time during the day and a lower
      physical activity level, less standing time and more lying time during the
      evening. The day-to-day variability in activity pattern is high and similar for
      both the patient and control group. CONCLUSION: The lower activity level
      especially found during the evening might indicate that patients need all their
      capacity to perform the tasks imposed during the day and as a consequence have
      less capacity left for their leisure time, in general the evening. This suggests
      the existence of an imbalance between the patient's physical capacity and the
      imposed environmental load. The large but similar day-to-day variability in
      activity pattern, which does not support the clinical findings of 'bad days' in
      CLBP patients, suggests the need for repeated measures.

PMID- 11841066
TI  - Beyond disability: perceived participation in people with a chronic disabling
      condition.
AB  - OBJECTIVE: To describe the impact of a chronic disabling condition on
      participation and to identify variables that may explain perceived restrictions
      in participation. STUDY DESIGN: Cross-sectional. SETTING: People were recruited
      from the outpatient clinics of two rehabilitation centres and the rehabilitation
      department of an academic hospital. SUBJECTS: One hundred and twenty-six people
      from five diagnostic groups (neuromuscular disease, rheumatoid arthritis, spinal
      cord injury, stroke, fibromyalgia) participated in the study. METHOD: The IPA
      (Impact on Participation and Autonomy) questionnaire was used to describe
      perceived participation. Explanatory variables were studied in terms of
      sociodemographic factors and health status variables. RESULTS: Some restrictions
      in participation seem comparable among diagnostic groups, others are specific to
      one or two groups. People with stroke, rheumatoid arthritis or fibromyalgia
      perceived more restrictions in participation than people with spinal cord injury
      or neuromuscular disorders. Emotional distress was the most important factor
      contributing to restrictions in participation. CONCLUSIONS: Perceived
      participation remains a complex concept in which many factors are involved. To
      make a contribution to meaningful participation of people with a chronic
      disabling condition, rehabilitation treatment should address physical, social,
      emotional and environmental aspects.

PMID- 11841067
TI  - Biocompatible membranes do not promote graft recovery following cadaveric renal
      transplantation.
AB  - BACKGROUND: Controversy surrounds the role of biocompatible membrane dialyzers in
      treatment of acute renal failure. Studies that have shown a benefit have involved
      critically ill patients where renal recovery and patient mortality are influenced
      by other comorbid disease. The aim of the present work is to clarify this issue
      in a more homogeneous population of patients with acute renal failure following
      cadaveric renal transplantation. METHODS: All patients with delayed graft
      function between January 1996 and February 1998 were randomized to receive either
      a biocompatible (BCM, polysulfone) membrane or bioincompatible (BICM, cuprophane)
      membrane for dialysis until onset of graft function. RESULTS: Forty-one patients
      were randomized, 23 to receive BCM and 18 BICM. Five patients (2 BCM, 3 BICM; p =
      NS) with primary non-function of graft were excluded from analysis, leaving 36
      cases of acute tubular necrosis (ATN). Patient and donor characteristics were
      similar in both groups. The BCM group had significantly longer periods of
      dialysis dependency compared to the BICM group (14 vs 10 days; p = 0.03). There
      was a tendency towards higher serum creatinine levels in the short term in the
      BCM group (318 vs 164 micromol/l at 1 month (p = 0.1), 190 vs 169 micromol/l at
      latest visit (p = 0.07)) and a greater number of acute rejection episodes in the
      BCM group (3.7 vs 1.7 episodes per 100 days of dialysis dependency, p = 0.1).
      With an intention-to-treat analysis of all 41 patients originally randomized,
      there was no significant difference in time to graft recovery between the 2
      groups (p = 0.18). CONCLUSIONS: In the setting of ARF posttransplantation, we
      have found no evidence to support the use of biocompatible membranes for
      dialysis. Rather, our study provides argument against a large benefit for the use
      of BCM in the recovery of ARF, as suggested by earlier studies.

PMID- 11841068
TI  - Early progressive interstitial fibrosis in human renal allografts.
AB  - BACKGROUND: Early fibrosis has been described in renal allografts and implicated
      in the progression of chronic allograft nephropathy (CAN). The precise factors
      implicated in the initiation and progression of early allograft fibrosis remain
      uncertain. PATIENTS AND METHODS: We studied retrospectively 23 cadaveric renal
      allograft recipients over a 3-year period, who had paired renal biopsies (Bx) (at
      implantation and as clinically indicated) within 3 months of transplantation
      (Tx). Eight of them have progressed over an average period of 3.16 +/- 0.83 years
      to CAN. Histological evaluation of interstitial fibrosis (IF) relied on point
      count analysis of Masson's trichrome (MT) staining as well as immunostainable
      collagens III (iCol III) and IV (iCol IV). The severity of the IF scores was
      correlated with the clinical, biochemical and histological parameters. The nature
      and severity of the interstitial inflammatory infiltrate were also evaluated by
      immunofluorescence. In addition, patients were subdivided into those whose
      fibrosis progressed (> 50% increase in IF/iCol IlI; Group 1) and non-progressors
      (< 50% increase in fibrosis score; Group 2) in an attempt to determine
      discriminatory features. RESULTS: In the whole group, there was a significant
      increase in the IF score, as estimated by MT staining and iCol III, from
      implantation to follow-up Bx (p = 0.0027 and p = 0.0088, respectively). The
      changes in iCol IV were not significant. Further, the increase in interstitial
      inflammatory infiltrate of total T lymphocytes, and not of macrophages, from
      implantation (modal category = 2) to follow-up (modal category = 0) was
      significant (p = 0.0121). The predictive value of such increase was significant
      (R2 = 0.617, p = 0.03). The donor's age (R2 = 0.892, p = < 0.0001), death from
      cerebrovascular accident (CVA) (R2 = 0.822, p = 0.047), as well as recipient's
      body weight (R2 = 0.892, p = 0.001), male gender (R2 = 0.687, p = 0.041) and
      elevated mean arterial pressure (MAP) (R2 = 0.892, p = < 0.0001) were all
      significant risk factors for early IF. Delayed graft function (DGF) proved to be
      a significant predictor of early IF (R2 = 0.822, p = 0.003) and became more
      significant in the presence of superimposed acute rejection (AR) (p = 0.0001).
      Proteinuria > 1 g/day (R2 = 0.882, p = 0.004) and hypertriglyceridemia > 2.25
      mmol/l (R2 = 0.808, p = < 0.0001) were also associated with early IF. Of the
      implantation histological parameters, iCol III proved to be a highly significant
      predictor of early IF (R2 = 0.892, p = < 0.0001). Interestingly, the predictive
      value of iCol III for graft survival in terms of CAN was significant (Cox p =
      0.088). Group 1 progressor patients (n = 10) were all males (p = 0.038) and
      received their kidneys from donors who died from CVAs in 90% of cases (p =
      0.011). They had, compared to non-progressors, a lower cyclosporin A level (p =
      0.047), a higher incidence of AR episodes (80% versus 54%), a higher serum
      creatinine at 10 days post-Tx (p = 0.005), a higher proteinuria (2.07 +/- 3.89
      g/l vs 0.96 +/- 0.97 g/l, p = 0.041) and a higher serum triglyceride (2.48 +/-
      1.37 mmol/l vs 1.69 +/- 0.81 mmol/l, p = 0.039) level. 8% of Group 1 patients had
      DGF compared to 30% in Group 2 (p = 0.023). Of note, the modal category of
      cytotoxic: helper T lymphocytes ratio was greater than 1 in Group 1 (2:1)
      patients and not in Group 2 (1:1). CONCLUSION: Implantation histology, and in
      particular iCol III, is a predictor of early IF in a subgroup of patients with
      DGF and AR. Additional risk factors include hypertension, proteinuria and
      hypertriglyceridemia especially in patients receiving kidneys from older donors
      who died of CVAs.

PMID- 11841069
TI  - Abstracts of the International Society for Heart and Lung Transplantation 22nd
      annual meeting. April 10-13, 2002. Washington, DC, USA.

PMID- 11841070
TI  - Fish chromatophores as cytosensors in a microscale device: detection of
      environmental toxins and bacterial pathogens.
AB  - Fish chromatophores from Betta splendens are used as the cytosensor element in
      the development of a portable microscale device capable of detecting certain
      environmental toxins and bacterial pathogens by monitoring changes in pigment
      granule distribution. The adaptation of chromatophores to a microscale
      environment has required the development of enabling technologies to produce
      miniaturized culture chambers, to integrate microfluidics for sample delivery, to
      miniaturize image capture, and to design new statistical methods for image
      analyses. Betta splendens chromatophores were selected as the cytosensor element
      because of their moderate size, their toleration of close contact, and most
      importantly, for their responses to a broad range of chemicals and pathogenic
      bacteria. A miniaturized culture chamber has been designed that supports
      chromatophore viability for as long as 3 months, and that can be easily
      transported without damage to the cells. New statistical methods for image
      analyses have been developed that increase sensitivity and also decrease the time
      required for detection of significant changes in pigment granule distribution.
      Betta chromatophores have been tested for their responses to selected pathogenic
      bacteria and chemical agents. We discuss in detail the aggregation of pigment
      granules seen when chromatophores are incubated with Bacillus cereus, a common
      cause of food poisoning. Also described are the more subtle responses of
      chromatophores to a class of environmental chemical toxins, polynuclear aromatic
      hydrocarbons. We show that the chromatophores are able to detect the presence of
      certain polynuclear aromatic hydrocarbons at concentrations lower than the
      Environment Protection Agency (EPA) 550.1 standards.

PMID- 11841071
TI  - Application of parallel liquid chromatography/mass spectrometry for high
      throughput microsomal stability screening of compound libraries.
AB  - Solution-phase and solid-phase parallel synthesis and high throughput screening
      have enabled biologically active and selective compounds to be identified at an
      unprecedented rate. The challenge has been to convert these hits into viable
      development candidates. To accelerate the conversion of these hits into lead
      development candidates, early assessment of the physicochemical and
      pharmacological properties of these compounds is being made. In particular, in
      vitro absorption, distribution, metabolism, and elimination (ADME) assays are
      being conducted at earlier and earlier stages of discovery with the goal of
      reducing the attrition rate of these potential drug candidates as they progress
      through development. In this report, we present an eight-channel parallel liquid
      chromatography/mass spectrometry (LC/MS) system in combination with custom Visual
      Basic and Applescript automated data processing applications for high throughput
      early ADME. The parallel LC/MS system was configured with one set of gradient LC
      pumps and an eight-channel multiple probe autosampler. The flow was split
      equivalently into eight streams before the multiple probe autosampler and
      recombined after the eight columns and just prior to the mass spectrometer ion
      source. The system was tested for column-to-column variation and for
      reproducibility over a 17 h period (approximately 500 injections per column). The
      variations in retention time and peak area were determined to be less than 2 and
      10%, respectively, in both tests. The parallel LC/MS system described permits
      time-course microsomal incubations (t(o), t5, t15, t30) to be measured in
      triplicate and enables estimations of t 1/2 microsomal stability. The parallel
      LC/MS system is capable of analyzing up to 240 samples per hour and permits the
      complete profiling up to two microtiter plates of compounds per day (i.e., 176
      test substrate compounds + sixteen controls).

PMID- 11841072
TI  - Far-lateral approach to intradural lesions of the foramen magnum without
      resection of the occipital condyle.
AB  - OBJECT: The goal of this study was to determine whether drilling out the
      occipital condyle facilitates surgery via the far-lateral approach by comparing
      data from 10 clinical cases with that from studies of eight cadaver heads.
      METHODS: During the last 6 years at Louisiana State University Health Sciences
      Center-Shreveport, 10 patients underwent surgery via the far-lateral approach to
      the foramen magnum. Six of these patients harbored anterior foramen magnum
      meningiomas, one patient a dermoid cyst, two patients vertebral artery (VA)
      aneurysms, and an additional patient suffered from rheumatoid disease of the
      craniocervical junction. The surgical approach consisted of retromastoid
      craniectomy and C-1 laminectomy. The seven tumors and the pannus of rheumatoid
      disease were completely excised, and the two aneurysms were clipped without
      drilling the occipital condyle. In one patient a chronic subdural hematoma was
      found 3 months after surgery, but no patient displayed any complication
      associated with surgery. It is significant that in no patient was a cerebrospinal
      fluid leak present. All patients experienced improved neurological function
      postoperatively. To compare surgical visibility, eight cadaveric specimens (16
      sides) were studied, including delineation of the VA and its segments around the
      craniocervical junction. Increase in visibility as a function of fractional
      removal of the occipital condyle was quantified by measuring the degrees of
      visibility gained by removing one third and one half of the occipital condyle.
      Removal of one third of the occipital condyle produced a mean increase of 15.9
      degrees visibility, and removal of one half produced a mean increase of 19.9
      degrees. CONCLUSIONS: On the basis of their findings the authors conclude that
      removal of the occipital condyle is not necessary for the safe and complete
      resection of anterior intradural foramen magnum tumors.

PMID- 11841073
TI  - Recurrent intraventricular and subarachnoid hemorrhage due to an intracranial
      schwannoma. Case illustration.

PMID- 11841074
TI  - Abstracts of the XIth Biennial Winter Workshop on Schizophrenia. Davos,
      Switzerland, February 24-March 1, 2002.

PMID- 11841077
TI  - Gynaecomastia.
AB  - Gynaecomastia is the commonest benign condition of the male breast. Management
      consists primarily of taking a complete history and making a thorough clinical
      examination. Ultrasound is recommended as the first-line imaging investigation
      although mammography may be added to confirm the diagnosis. The results of fine
      needle aspiration cytology may be poor as an adequate yield of pathological
      specimens is low, and it should be reserved for suspected malignant lesions.
      Endocrine evaluation of gynaecomastia is rarely productive and such testing is
      best done selectively. Many patients can be treated simply with reassurance about
      the benign nature of the condition. In those patients in whom a stimulus has been
      identified modification of treatment may improve symptoms. Hormonal manipulation
      may be appropriate in younger patients, but a testicular neoplasm must be
      excluded. Operations should be reserved for those who fail to respond to hormones
      and in those with severe cosmetic deformities.

PMID- 11841075
TI  - Ethnicity and treatment response in schizophrenia: a comparison of 3 ethnic
      groups.
AB  - BACKGROUND: Numerous cultural and ethnic factors may directly and indirectly
      influence treatment outcome in schizophrenia. The present study compared the
      response to antipsychotic treatment in 3 ethnic groups of patients with
      schizophrenia. METHOD: Fifty black, 63 mixed descent, and 79 white patients with
      DSM-IV-diagnosed schizophrenia or schizophreniform disorder who were participants
      in multinational clinical drug trials were assessed by means of the Positive and
      Negative Syndrome Scale (PANSS). Treatment response was measured by the change in
      PANSS total scores and the change in positive, negative, and general
      psychopathology subscale scores from baseline to 6 weeks. Also, the percentage of
      responders (defined as > or = 40% reduction in PANSS total scores) was calculated
      for each group. RESULTS: Baseline PANSS scores differed significantly, being
      higher for black and mixed descent patients. Mixed descent patients showed the
      greatest mean +/- SD percentage reduction in PANSS total score (29.4 +/- 21.6)
      followed by black (28.4 +/- 14.7) and white (11.4 +/- 27.6) patients. Analysis of
      covariance revealed a significant effect of ethnicity on the reduction in PANSS
      total scores (p < .0001). The numbers of responders were 20 mixed descent (32%),
      12 black (24%), and 7 white (9%) patients (p = .002). CONCLUSION: Significant
      ethnic differences in acute antipsychotic treatment response are demonstrated by
      this study. Factors such as diet, nutritional status, body mass, and substance
      use could be important, as well as genetically determined ethnospecific
      pharmacokinetic and pharmacodynamic differences. Delayed help-seeking may account
      for the higher baseline scores in the black and mixed descent patients.

PMID- 11841078
TI  - Imaging of experimental end-to-side anastomoses in a cast model.
AB  - OBJECTIVE: To evaluate cast models in the imaging of experimental end-to-side
      anastomoses. DESIGN: Experimental study. SETTING: Teaching hospital, Finland.
      INTERVENTIONS: 20 non-stenosed and 10 stenosed end-to-side anastomoses were
      constructed using a Dacron prosthesis 8 mm in diameter. Cast models were made of
      all anastomoses, and anteroposterior and oblique projection radiographs were
      taken of them. Cross-sectional radiographs were also taken of the stenosed
      anastomoses. MAIN OUTCOME MEASUREMENTS: The diameters and areas of anastomoses
      were measured on the radiographs and compared with the corresponding measurements
      of the casts. RESULTS: No filling defects were observed in any of the cast models
      and only minor differences were found between the corresponding measurements of
      the anteroposterior and oblique projection radiographs and casts. The lower
      density of the contrast medium in the stenotic anastomoses indicated a stenosis.
      In the cross-sectional radiographs of the stenotic anastomoses there was a
      significant reduction (p < 0.001) both in the diameter and the area, the mean of
      which was 63% and the median 61%. CONCLUSIONS: Radiographs of cast models look
      promising in imaging of experimental end-to-side anastomoses when cross-sectional
      projections are also used.

PMID- 11841079
TI  - Preoperative bowel preparation with meglumine and sodium diatrizoate
      (Gastrografin): a prospective randomised comparison.
AB  - OBJECTIVE: To test the use of meglumine and sodium diatrizoate (Gastrografin) as
      an agent for preoperative mechanical bowel preparation. DESIGN: Prospective
      randomised comparison. SETTING: County general hospital, Greece. SUBJECTS: 58
      patients listed for elective colorectal operations were randomly divided into 2
      groups. The first (n = 30) was given Gastrografin 200 ml orally for 2 consecutive
      days before operation, and the second (n = 28) was given Ringer's solution
      through a nasogastric tube. MAIN OUTCOME MEASURES: Tolerability, acceptability,
      quality of cleansing, and complications. RESULTS: There were no disturbances in
      electrolyte concentrations, and other laboratory variables also remained
      unchanged. Two patients treated with Ringer's solution had appreciable increases
      in arterial blood pressure, but there were no significant overall changes. About
      half the patients given Ringer's felt nauseated and a third vomited. Such
      symptoms were uncommon in patients treated with Gastrografin (p < 0.01). 28/30
      and 26/28 (93%) had a clean colonic lumen at operation, whereas in the reminder
      the lumen was evaluated as containing "slight residue". There were no operation
      related complications. CONCLUSIONS: Gastrografin can be used successfully as an
      agent for mechanical bowel preparation before elective colorectal surgery, as it
      gives equally good cleansing results compared with the established method of
      whole gut irrigation. It also seems to be better tolerated and accepted by
      patients.

PMID- 11841080
TI  - Incisional hernia repair: tensiometry for the selection of the appropriate
      procedure.
AB  - OBJECTIVE: To audit the early and late results of repairs of incisional hernias
      before and after the introduction of peroperative tensiometry. DESIGN:
      Retrospective study. SETTING: University hospital, Germany. PATIENTS: 675
      operations on 553 patients in 18 years. INTERVENTIONS: Before we introduced
      tensiometry we closed 560 incisional hernias by direct suture and 63 by the inlay
      onlay technique. Since we took up tensiometry the numbers were 9 and 43,
      respectively. MAIN OUTCOME MEASURES: Postoperative complications including
      recurrences. RESULTS: Recurrences developed in 246/560 (44%) after direct suture
      in the early series, compared with 2/9 (22%) after adoption of tensiometry. After
      inlay-onlay operations there were 4/63 (6%) recurrences before, and 1/43 (2%)
      after adoption of tensiometry. CONCLUSIONS: Tensiometry allows the surgeon to
      tailor his operation to the conditions that he finds during the operation.

PMID- 11841081
TI  - Biomechanical and morphological types of the linea alba and its possible role in
      the pathogenesis of midline incisional hernia.
AB  - OBJECTIVE: To review the tensile strength of the different histological types of
      fibres in the linea alba and correlate the anatomical features of the anterior
      abdominal wall with the tensile strength of the linea alba to see whether the
      tensile strength of the linea alba might contribute to the development of midline
      incisional hernias. DESIGN: Laboratory study. SETTING: University hospital,
      Germany. SUBJECTS: 46 cadavers in part one, and 9 freshly frozen and 38 formalin
      fixed cadavers in part two. INTERVENTIONS: In the first part of the study the
      histological examination was by binocular dissection microscopy, magnification
      x10, but this was not sufficiently reproducible so in the second part we used an
      Olympus BX50 microscope, magnification x20, and Optimas 5.22 picture processing
      software. Tensile strength was measured using a Loosenhausen ZHP 1-6 tensiometer.
      MAIN OUTCOME MEASURES: Correlation between anatomical features and tensile
      strength. RESULTS: The method used in part one of the study failed to
      differentiate between the three types of fibres in the linea alba (weak,
      intermediate, and compact). In the second part of the study we found that the
      fibres were irregular, with no systematic crossing of the fibres of the
      aponeurosis. There was a significant correlation between the thickness and
      density of fibres in the linea alba and its tensile strength (r = 0.9). The
      thickness of fibres ranged from 21.9-38.2 microm and the density from 48% to 90%.
      The tensile strength ranged from 3-25 kp. CONCLUSION: A combination of low
      density and thin fibres in the linea alba could be a predisposing factor for
      development of midline incisional hernias

PMID- 11841082
TI  - Multiple adenomatous polyps of the gallbladder presenting as carcinoma of the
      gallbladder.

PMID- 11841083
TI  - Emphysematous pancreatitis.

PMID- 11841085
TI  - A rare fistula: obturator hernia producing a colocutaneous fistula.

PMID- 11841084
TI  - Anaphylaxis after peritumoral injection of sulphan blue 1% for identification of
      the sentinel node in lymphatic mapping of the breast.

PMID- 11841086
TI  - Giant cystic lymphangioma of the stomach.

PMID- 11841087
TI  - Physiological mass measurements on Skylab 1/2 and 1/3.
AB  - Mass measurements of crewmen and objects were made for the first time in space
      during Skylab. A description of the new devices designed for such measurements
      and of the technique of their use is detailed. Results from ground-based chamber
      simulation tests and from those during Skylab II and III show similar patterns of
      simple metabolic deficits, of a rapid loss during the first few days of flight
      followed by a reciprocal gain for the first few postflight days, and other
      transient changes. It is concluded that two major causes of weight loss are
      present: (1) a fluid redistribution and loss, and (2) metabolic losses. Added to
      these are short-term changes from transient stress. Smaller, simpler, and cheaper
      devices have since been designed which should allow mass measurements on
      virtually any object in almost any spacecraft.

PMID- 11841088
TI  - Endocrine responses in long-duration manned space flight.
AB  - The bioassay of body fluids experiment is designed to evaluate the biochemical
      adaptation resulting from extended exposure to space flight environment by
      identifying changes in hormonal and associated fluid and electrolyte parameters
      reflected in the blood and urine of the participating crewmen. The combined
      stresses of space flight include weightlessness, acceleration, confinement,
      restraint, long-term maintenance of high levels of performance, and possible
      desynchronosis. Endocrine measurements to assess the physiological cost of these
      stresses have been considered from two aspects. Fluid and electrolyte balance
      have been correlated with weight loss, changes in the excretion of aldosterone
      and vasopressin and fluid compartments. The second area involves the estimation
      of the physiological cost of maintaining a given level of performance during
      space flight by analysis of urinary catecholamines and cortisol. Inter-individual
      variability was demonstrated in most experimental indices measured; however,
      constant patterns have emerged which include: body weight change; increases in
      plasma renin activity; elevations in urinary catecholamines, ADH, aldosterone and
      cortisol concentrations. Plasma cortisol decreases in immediate postflight
      samples with subsequent increase in 24-hour urines. The measured changes are
      consistent with the prediction that a relative increase in thoracic blood volume
      upon transition to the zero-gravity environment is interpreted as a true volume
      expansion resulting in an osmotic diuresis. This diuresis in association with
      other factors ultimately results in a reduction in intravascular volume, leading
      to an increase in renin and a secondary aldosteronism. Once these compensatory
      mechanisms are effective in reestablishing positive water balance, the crewmen
      are considered to be essentially adapted to the null-gravity environment.
      Although the physiological cost of this adaptation must reflect the electrolyte
      deficit and perhaps other factors, it is assumed that the compensated state is
      adequate for the demands of the environment; however, this new homeostatic set is
      not believed to be without physiological cost and could, except with proper
      precautions, reduce the functional reserve of exposed individuals.

PMID- 11841089
TI  - Bone mineral measurement: Skylab experiment M-078.
AB  - The observation that bone mineral is lost in patients who are either immobilized
      or remain in bed for extended periods of time formed the basis for the concern
      that large amounts of bone mineral may be lost during long periods of
      weightlessness. This concern was magnified when early X-ray densitometry studies
      suggested that rather large amounts of mineral could be lost during rather short
      periods of weightlessness (4-14 days). Even though these Gemini results have
      recently been modified, they still reflect substantial losses in the upper
      extremity. This led to a series of prolonged bed-rest studies (30-36 weeks)
      which, in addition to careful calcium balance, also employed a newer, more
      precise method of estimating bone mineral in the radius, ulna, and os calcis. It
      employed an essentially monoenergetic photon source (125I) and a scintillation
      detector operating in a rectilinear scanning mode to measure bone mineral by the
      absorptiometric technique. Bed-rest studies revealed variable mineral losses but
      suggested that little if any is lost during 4-6 weeks, with variable amounts
      being lost in 8 weeks. Losses up to 40% were noted in the os calcis after 9
      months, with essentially none in the radius and ulna. When this technique was
      employed during the Apollo 14, 15, and 16 missions, only one crewman (CMP Apollo
      15) showed significant losses in the os calcis and none in the radius or ulna.
      These results were, therefore, in concert with the bed-rest data but at variance
      with the earlier Gemini data. The variability observed during bed rest was
      reconciled when it was observed that the rate of loss could be correlated with
      the initial 24-hour urinary hydroxyproline excretion and the initial os calcis
      mineral content. Prediction terms were established. Measurements of the SL-II
      crew after 28 days of weightlessness revealed no significant bone mineral losses.
      The Skylab data lie within the predicted limits obtained from the bed-rest data.
      The relevance of the prediction terms to the Skylab and longer missions
      discussed.

PMID- 11841090
TI  - Skylab experiment results: hematology studies.
AB  - These studies were designed and coordinated to evaluate specific aspects of man's
      immunologic and hematologic systems which might be altered by or respond to the
      space flight environment. The biochemical functions investigated included
      cytogenetic damage to blood cells, immune resistance to disease, regulation of
      plasma and red cell volumes, metabolic processes of the red blood cell, and
      physical chemical aspects of red blood cell functions. Only minor changes were
      observed in the functional capacity of erythrocytes as determined by measuring
      the concentrations of selected intracellular enzymes and metabolites. Tests of
      red cell osmotic regulation indicated some elevation in the activity of the
      metabolic dependent Na-K pump, with no significant alterations in the cellular Na
      and K concentrations or osmotic fragility. A transient shift in red cell specific
      gravity profile was observed on recovery, possibly related to changes in cellular
      water content. Measurements of hemoconcentration (hematocrit, hemoglobin
      concentration, red cell count) indicated significant fluctuations postflight,
      reflecting observed changes in red cell mass and plasma volume. There was no
      apparent reticulocytosis during the 18 days following the first manned Skylab
      mission in spite of a significant loss in red cell mass. However, the
      reticulocyte count and index did increase significantly 5 to 7 days after
      completion of the second, longer duration, flight. There were no significant
      changes in either the while blood cell count or differential. However, the
      capacity of lymphocytes to respond to an in vitro mitogenic challenge was
      repressed postflight, and appeared to be related to mission duration. The cause
      of this repression is unknown at this time. Only minor differences were observed
      in plasma protein patterns. In the second mission there were changes in the
      proteins involved in the coagulation process which suggested a hypercoagulative
      condition.

PMID- 11841091
TI  - Individual differences in susceptibility to motion sickness among six Skylab
      astronauts.
AB  - One of the Skylab experiments dealt with motion sickness, comparing
      susceptibility in the workshop aloft with susceptibility preflight and
      postflight. Tests were conducted on and after mission-day 8 (MD 8) by which time
      the astronauts were adapted to working conditions. Stressful accelerations were
      generated by requiring the astronauts, with eyes covered, to execute standardized
      head movements (front, back, left, and right) while in a chair that could be
      rotated at angular velocities up to 30 rpm. The selected endpoint was either 150
      discrete head movements or a very mild level of motion sickness. In all rotation
      experiments aloft, the five astronauts tested (astronaut 1 did not participate)
      were virtually symptom free, thus demonstrating lower susceptibility aloft than
      in preflight and postflight tests on the ground when symptoms were always
      elicited. Inasmuch as the eyes were covered and the canalicular stimuli were the
      same aloft as on the ground, it would appear that lifting the stimulus to the
      otolith organs due to gravity was an important factor in reducing susceptibility
      to motion sickness even though the transient stimuli generated under the test
      conditions were substantial and abnormal in pattern. Some of the astronauts
      experienced motion sickness under operational conditions aloft or after
      splashdown, but attention is centered chiefly on symptoms manifested in zero
      gravity. None of the Skylab-II crew (astronauts 1 to 3) was motion sick aloft.
      Astronaut 6 of the Skylab-III crew (astronauts 4 to 6) experienced motion
      sickness within an hour after transition into orbit; this constitutes the
      earliest such diagnosis on record under orbital flight conditions. The eliciting
      stimuli were associated with head and body movements, and astronaut 6 obtained
      relief by avoiding such movements and by one dose of the drug combination 1
      scopolamine 0.35 mg + d-amphetamine 5.0 mg. All three astronauts of Skylab-III
      experienced motion sickness in the workshop where astronaut 6 was most
      susceptible and astronaut 4, least susceptible. The higher susceptibility of SL
      III crewmen in the workshop, as compared with SL-II crewmen, may be attributable
      to the fact that they were based in the command module less than one-third as
      long as SL-II crewmen. The unnatural movements, often resembling acrobatics,
      permitted in the open spaces of the workshop revealed the great potentialities in
      weightlessness for generating complex interactions of abnormal or unusual
      vestibular and visual stimuli. Symptoms were controlled by body restraint and by
      drugs, but high susceptibility to motion sickness persisted for 3 days and
      probably much longer; restoration was complete on MD 7. From the foregoing
      statements it is clear that on and after MD 8 the susceptibility of SL-II and SL
      III crewmen to motion sickness under experimental conditions was
      indistinguishable. The role played by the acquisition of adaptation effects prior
      to MD 8 is less clear and is a subject to be discussed.

PMID- 11841092
TI  - Recent advances in the physiology of whole body immersion.
AB  - Recent investigations have furnished a complete analysis of the hemodynamic
      events accompanying whole-body immersion. About 700 ml of blood are translocated
      into the intrathoracic circulation, and heart volume increases by 180 +/- 62 ml.
      These changes are followed by an increase in stroke volume and cardiac output of
      over 30%. At the same time a reflex reduction of total peripheral resistance and
      venous tone occurs. Renin and aldosterone activity are reduced while the 17
      hydroxycorticosteroid is not affected. Treatment of the subject with DOCA
      attenuates but does not extinguish the excess sodium excretion of immersion. This
      finding strengthens the arguments in favor of an unknown factor enhancing sodium
      excretion. Finally, the relative activation of the three factors that serve
      volume control, the excretory function of the kidney, capillary filtration
      pressure, and the thirst mechanism, is discussed.

PMID- 11841093
TI  - Long-term biological investigations in space.
AB  - Missions in space within the next two decades will be of longer duration than
      those carried out up to the present time, and the effects of such long-term
      flights on biological organisms are unknown. Results of biological experiments
      that have been performed to date cannot be extrapolated to results in future
      flights because of the unknown influence of adaptation over a long period of
      time. Prior experiments with Axolotl, fishes, and vertebrates by our research
      team (in part with sounding rockets) showed that these specimens did not appear
      to be suitable for long-term missions on which minimization of expense,
      technique, and energy is required. Subsequent investigations have shown the
      suitability of the leech (Hirudo medicinalis), which consumes blood of mammals up
      to ten times its own weight (1 g) and can live more than 2 years without further
      food supply. Emphasis in the experiments with Hirudo medicinalis is placed on
      metabolic rhythm and motility. Resorption and diffusion in tissue, development,
      and growth under long-term effects of cosmic proton radiation and zero-gravity
      are other focal points. The constancy of cellular life in the mature animals is a
      point in favor of these specimens. We have also taken into account the
      synergistic effects of the space environment on the problems just mentioned. The
      life-support system constructed for the leech has been tested successfully in
      four sounding rocket flights and, on that basis, has been prepared for a long
      term mission. Long-term investigations out of the terrestrial biosphere will
      provide us with information concerning the degree of adaptation of certain
      physiological and biochemical functions and as to what extent biological
      readjustment or repair processes can occur under the specific stress conditions
      of space flight.

PMID- 11841094
TI  - Vestibular function in the space environment.
AB  - Adaptation to the weightless state and readaptation after space flight to the 1-G
      environment on the ground are accompanied by various transitory symptoms of
      vestibular instability, kinetosis, and illusory sensations. Aside from the
      problem of how to treat and if possible prevent such symptoms, they offer a clue
      to a better understanding of normal vestibular functions. Weightlessness is a
      powerful new "tool" of vestibular research. Graybiel reported as early as 1952
      that human subjects observed the illusion that a real target and the visual
      afterimage seemed to raise in the visual field during centrifugation when the
      subjects were looking toward the axis of rotation (oculogravic illusion). In
      aircraft parabolic-flight weightlessness, human subjects observed that fixed real
      targets appeared to have moved downward while visual afterimages appeared to have
      moved upward (oculoagravic illusion). It can be shown by electronystagmography as
      well as by a method employing double afterimages that part of this illusion is
      caused by eye movements that are triggered by the changing input from the otolith
      system. Another part of the illusion is based on a change of the subjective
      horizontal and must be caused by convergence of vestibular and visual impulses
      "behind" the eyes. This part was measured independently of the first one by using
      a new method. Eye movements could be prevented during these experiments by
      optical fixation with the right eye on a target at the end of a 24-in. long tube
      which was rigidly attached parallel to the longitudinal axis of an aircraft. At
      the same time the subject tried to line up a shorter tube, which was pivoting
      around his left eye, with the subjective horizon.

PMID- 11841095
TI  - Development of Skylab medical equipment and flight preparations.
AB  - The purpose of this report is to provide an introduction and overview of the
      Skylab medical program. Some of the more important medical systems and equipment
      provided for crew sustenance are described. The major inflight medical
      experiments are reviewed, and the test programs are discussed. The medical
      operations procedures and the techniques used to monitor crew health are reviewed
      to provide an understanding of the medical management of this complex mission.

PMID- 11841096
TI  - Weightlessness: a case history.
AB  - The facts presented represent, for convenience, a composite clinical picture of
      the three crewmen aboard Skylab II as observed by me.

PMID- 11841097
TI  - Quantitative electrocardiography during extended space flight.
AB  - To assess the effects of prolonged space flight on the electrophysiological
      properties of the heart, vectorcardiograms (VCG) were obtained on the Skylab
      crews at regular intervals during flight and the pre- and postflight periods. The
      VCG signals were telemetered from Skylab and analyzed by digital computer.
      Conventional 12-lead electrocardiograms were derived from the VCG signals by a
      lead transformation program. Standardized exercise loads were incorporated into
      the experiment protocol to increase the sensitivity of the VCG for effects of
      deconditioning and to detect susceptibility for arrhythmias. In Skylab II, 24
      preflight, 21 inflight, and 19 postflight experiments were analyzed.
      Statistically significant inflight changes observed in two or more crew members
      included: decreased resting heart rate, increased QRS duration, anterior shift
      QRS vector, increased QRS vector magnitude, anterior shift T vector, and
      increased T vector magnitude. One astronaut had occasional premature ventricular
      contractions (PVC) during the pre- and postflight phases. He had a single episode
      of multiple PVC's during heavy-load exercise testing in flight. A second
      astronaut had no arrhythmia during pre- or inflight testing. On postflight day 21
      he had multiple PVC's and salvos of ectopic ventricular beats. He has had no
      recurrence of the arrhythmia. With the exception of the cardiac arrhythmias, no
      deleterious electrophysiological changes were observed during Skylab II.

PMID- 11841098
TI  - Papers presented at the Fifth International Symposium on Basic Environmental
      Problems of Man in Space, Washington, D.C., 27-30 November 1973.

PMID- 11841099
TI  - Israeli-Palestinian conflict. Health consequences of Israeli settlements in
      occupied lands.

PMID- 11841100
TI  - Conflict in Sri Lanka. Doctors can influence people and promote peace.

PMID- 11841101
TI  - 2001 Claude Bernard Lecturer. Philip E. Cryer.

PMID- 11841102
TI  - Markets in health care: individualistic values versus communitarian claims.

PMID- 11841103
TI  - What kinds of people should we create?
AB  - The advent of genetic engineering will give people the power to design the
      members of the succeeding generation, and thus will render practical the issue
      how such a power ought to be exercised. Here I address that issue in a general
      way. I point out that the aim of making future people better adapted to the
      modern social environment is implicitly circular, since the natures of the
      peoples themselves will determine the nature of the social environment. I claim
      that the human property the enhancement of which would do most to enrich
      experience is intelligence; accordingly increased intelligence should be a
      primary aim of genetic designers. The tendency to feel pain should be attenuated,
      as positive motivation is substituted for negative (to some extent). People
      should be designed so as to be motivated more by reason than by any non-rational
      drives (though rational motivation may still involve pleasure and pain). The sex
      drive, having outlived its usefulness, will probably be replaced by some other
      source of pleasure. As a side effect of these changes in people, the arts and
      social sciences will be transformed beyond recognition.

PMID- 11841104
TI  - What if prospective clients knew how managed care impacts psychologists' practice
      and ethics? An exploratory study.
AB  - Modal responses to items from a recent survey of independent practitioners
      regarding the impact of managed care on their practices and ethics (Murphy,
      DeBernardo, & Shoemaker, 1998) were presented to participants as the responses of
      a hypothetical independent practitioner. Participants were asked to consider
      seeing this hypothetical practitioner both before and after being informed of the
      practitioner's responses to the managed care survey. Results indicate that when
      participants were informed of the practitioner's views toward managed care, their
      own attitudes toward therapy changed significantly. Specifically, compared to
      uninformed participants, informed participants were significantly more likely to
      believe that managed care would have a negative impact on treatment and
      significantly less likely to see an independent practitioner, use insurance
      benefits, expect to benefit from treatment, expect to form a strong working
      relationship, and trust that the practitioner would work in their best interest.
      Implications regarding ethics and informed consent are discussed.

PMID- 11841105
TI  - Through the community looking glass: reevaluating the ethical and policy
      implications of research on adolescent risk and sociopathology.
AB  - Drawing on a conception of scientists and community members as partners in the
      construction of ethically responsible research practices, this article urges
      investigators to seek the perspectives of teenagers and parents in evaluating the
      personal and political costs and benefits of research on adolescent risk
      behaviors. Content analysis of focus group discussions involving over 100 parents
      and teenagers from diverse ethnic and socioeconomic backgrounds revealed
      community opinions regarding the scientific merit, social value, racial bias, and
      participant and group harms and benefits associated with surveys, informant
      reports, intervention studies, blood sampling, and genetic research on youth
      problems. Participants comments highlight new directions for socially responsible
      research.

PMID- 11841106
TI  - LET distributions from CR-39 plates on Space Shuttle missions STS-84 and STS-91
      and a comparison of the results of the CR-39 plates with those of RRMD-II and
      RRMD-III telescopes.
AB  - The LET distributions during the Space Shuttle missions STS-84 (altitude 270-412
      km, average 375 km; inclination angle, 51.6 degrees) and STS-91 (altitude 328-397
      km, average 373 km; inclination angle, 51.6 degrees) were measured using CR-39
      plastic nuclear track detectors. A correction for the dip-angle dependence of the
      track-formation sensitivity of the CR-39 plates was applied to the data analysis.
      The absorbed doses and the dose equivalents around RRMD Detector Units, estimated
      from the LET distributions in the LET region of 4-200 keV/micrometers, fluctuated
      with standard deviations of +/- 21% to +/- 35% in both flight experiments. The
      LET distributions obtained from the CR-39 plates agreed well with that obtained
      from RRMD-II in STS-91. However, the particle fluxes obtained from RRMD-III in
      STS-84 and STS-91 were two or three times higher than those obtained from RRMD-II
      and the CR-39 plates. It was concluded that the LET distributions obtained from
      RRMD-II and the CR-39 plates in the present flight experiments did not include
      the contribution of target-fragmented secondary heavy particles produced by low
      LET particles, such as relativistic or semi-relativistic protons and helium ions,
      whereas RRMD-III was able to detect these secondary particles because of its low
      triggering level.

PMID- 11841107
TI  - Analysis of the calibration results obtained with Liulin-4J spectrometer
      dosimeter on protons and heavy ions.
AB  - We are developing a portable dosimeter (Liulin-4J) based on a silicon
      semiconductor detector for use in measuring the absorbed dose from primary or
      secondary cosmic rays to astronauts and airplane crews. The dosimeter can measure
      not only the flux and dose rate, but also the deposited energy spectrum for
      silicon in per unit time. In order to calibrate the dosimeter, we have carried
      out exposures at the NIRS cyclotron and HIMAC heavy ion synchrotron facilities.
      We obtained a detector response function for using in measuring energy deposition
      and LET.

PMID- 11841108
TI  - Comparison between superficial and deep acupuncture in the treatment of the
      shoulder's myofascial pain: a randomized and controlled study.
AB  - The principle aim of the present work is the evaluation of the importance of the
      variable "depth" of needle insertion in the determination of acupuncture's
      therapeutic results. A randomized clinical trial carried out on 44 patients
      belonging to two groups of 22 each, suffering from shoulder myofascial pain:
      group A: superficial acupuncture; group B: deep acupuncture. All of them
      subjected to the same model of treatment with 13 needles and the treatment of the
      most painful 4 trigger points (TP) found in the shoulder's area. In the group A
      patients, the needles were introduced in the skin at a depth of 2 mm, on the TP.
      In the group B patients, the needles were placed deeply both in the muscular
      acupuncture points and in the TP. The treatment was planned for a cycle of 8
      sessions, the first 4 to be performed twice a week, the last 4 weekly. The
      intensity of pain was evaluated with the McGill Pain Questionnaire before
      beginning the therapy, at the end of the therapy, and at the follow-up after 1
      and 3 months. Both techniques had efficacy in controlling pain. A statistically
      significant difference rose between the two needling techniques at the end of the
      treatment and at the follow up after one and three months. Deep acupuncture shows
      to be better at all times and this underlines the importance of the muscular
      afferences in acupunctural stimulation in the control of pain.

PMID- 11841109
TI  - Effect of manual acupuncture and transcutaneous electrical nerve stimulation on
      the H-reflex.
AB  - Several studies find that manual acupuncture and transcutaneous electrical nerve
      stimulation (TENS) are via different mechanisms and generate different effect on
      the central nervous system, therefore, the aim of the present study was to
      compare the effect of manual acupuncture (MA) and TENS on the spinal cord using H
      reflex recordings. A total of 13 healthy adult volunteers were studied. The
      electrical stimuli were delivered to the posterior tibial nerve transcutaneously
      at the left popliteal fossa to evoke the soleus H-reflex. MA, 2Hz TENS, 100 Hz
      TENS, respectively, was applied to the surface of the right first dorsal
      interosseous muscle exactly at the Hegu acupoint (LI.4). Four assessments were
      performed randomly, separated by an interval of at least three days in all the
      subjects as follows: 1) Control assessment: a pair of electrodes placed on the
      surface of the right Hegu acupoint (LI.4), but no electrical stimulation was
      delivered throughout the test; 2) MA assessment: MA was done at the right Hegu
      acupoint (LI.4) for 15 minutes; 3) TENS assessment at 2Hz: electrical stimulation
      (40 mA in intensity) at 2Hz was applied to the surface of the right Hegu acupoint
      (LI.4) for 15 minutes; 4) TENS assessment at 100 Hz: electrical stimulation (20
      mA in intensity) at 100 Hz was applied to the surface of the right Hegu acupoint
      (LI.4) for 15 minutes. Each assessment was divided into three periods as follows:
      1) Baseline period: H-reflexes recorded prior to MA or TENS; 2) TENS period: six
      H-reflex recordings after MA or TENS for a duration of 4-5 min, 9-10 min and 14
      15 min, respectively; 3) Post TENS period: H-reflex recordings of 6 after TENS
      period 4-5 min and 9-10 min, respectively. Our results indicate that both 2Hz
      TENS and 100 Hz TENS increased the amplitude of the H-reflex, and that these
      increases may be retained longer with 100 Hz TENS than with 2 Hz TENS, whereas MA
      could not increase the amplitude of the H-reflex. MA, TENS at 2 Hz or 100 Hz
      didn't change the latencies of the H-reflexes. We conclude that both 2Hz and 100
      Hz TENS increased the amplitude of the H-reflex, suggesting that TENS enhances
      the excitability of the motoneuron pool in the spinal cord, and 100 Hz TENS has a
      greater effect than 2Hz TENS, whereas MA was not similar effect to TENS on spinal
      cord.

PMID- 11841110
TI  - Monitoring of muscle fatigue during isokinetic exercise.
AB  - The aim of this study was to evaluate and clarify the usefulness of different
      spectral characteristics of myoelectrical activity in the follow-up of
      development of muscle fatigue. Vastus lateralis (part of quadriceps) muscle
      loaded in a simple isokinetic exertion test was used as a model. Twelve, well
      trained athletes served as study subjective to minimize the inter-individual
      variations. They went through one-minute test with isokinetic device at the range
      of 90 degrees extension and flexion at the level of their maximal force. The
      myoelectrical signals were registered from middle of the vastus lateralis muscle
      by a computerized fast Fourier transform analyzing system based on 80286 and
      80287 microprocessors and using surface electrodes. Mean power frequency (MPF)
      was 65.6 (SE=Standard Error, 1.6) Hz, median frequency (MF) 55.8 Hz and zero
      crossing rate (ZCR) 92.5 (SE 1.5) during first performance. All these parameters
      decreased apparently linearly and significantly from the beginning of the test
      (P<0.001). The decrease rate of ZCR was fastest and MF slowest. The area of power
      spectrum (PSA) was 1753 (SE 320) units during first performance, and it increased
      markedly with slightly accelerating rate during the test. In conclusion, for the
      evaluation of the muscular performance during the development of fatigue it is
      beneficial to monitor simultaneously MPF, MF and ZCR.

PMID- 11841111
TI  - Atlanto-axial subluxation syndrome and management of intractable headache, neck
      pain and shoulder pain with auricular stimulation: a clinical case report.
AB  - Atlanto-axial subluxation syndrome is a condition that is easily overlooked,
      misdiagnosed and mismanaged. Anatomy, neurovascular involvement and description
      of clinical manifestations are reviewed. Bi-Digital O-Ring Test is employed to
      establish an accurate diagnosis and its value and accuracy described briefly. Bi
      Digital O-Ring Test has been an important diagnosis confirmation method
      (reconfirmed by CT or MRI in over 95% of more than 850 clinical cases) in this
      author's practice of spinal disorder and intractable pain management. A newly
      described device, the KIM-STIM, offers auricular stimulation of multiple points,
      using electrical microcurrent. Each unit is individually custom-molded to the
      patient's ear, and fitted with multiple electrodes. It was found to be very
      effective in managing the majority of intractable pain, especially pain requiring
      multiple daily treatments in order for the patient to live and function normally.
      The KIM-STIM device allows the patient to self-manage the pain, by day or night,
      thus allowing for a reduction or elimination of medication intake and diminishing
      the necessity for frequent doctor visits.

PMID- 11841112
TI  - Minor methylated pyranoamentoflavones from Calophyllum venulosum.
AB  - Two new biflavonoids, pyranoamentoflavone 7-methyl ether (1) and
      pyranoamentoflavone 4'-methyl ether (2), have been isolated from the leaves of
      Calophyllum venulosum. The structures of these two new compounds were elucidated
      by spectroscopic data.

PMID- 11841113
TI  - New galactolipids from the marine bacillariophycean microalga Nitzschia sp.
AB  - Two new galactopyranosyldiacylglycerols have been isolated from the marine
      bacillariophycean microalga Nitzschia sp. and their structures were determined as
      (2S)-3-O-beta-D-galactopyranosyl-1,2-di-O-(9Z-hexadecenoyl)glycerol (1) and (2S)
      3-O-beta-D-galactopyranosyl-1-O-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-2-O-(9Z
      hexadecenoyl)glycerol (2) by physicochemical evidence.

PMID- 11841114
TI  - A new antibacterial diterpene from the roots of Salvia caespitosa.
AB  - From the roots of Saliva caespitosa Montbret and Aucher ex. Bentham a new
      diterpene 6beta-hydroxyisopimaric acid (1) has been isolated together with four
      known diterpenes, one new triterpenoid, 3-acetylvergatic acid (2), as well as
      five known triterpenoids, two steroids and a flavone. The structures of the
      compounds were established by spectroscopic analyses. The isolated compounds were
      tested against standard bacterial strains. Only the new diterpene, 6beta
      hydroxyisopimaric acid has strong activity (MIC 9 microg/ml) against S. aureus
      and (MIC 18 microg/ml) against S. epidermidis as well as against B. subtilis (MIC
      9 microg/ml).

PMID- 11841115
TI  - A new biologically active triterpenoid saponin from the leaves of Lepidagathis
      hyalina Nees.
AB  - A new biologically active triterpenoid saponin m.f. C42H68O13, m.p. 315 degrees
      317 degrees C was isolated from the ethyl acetate soluble fraction of the
      methanolic extract of the leaves of Lepidagathis hyalina. Its structure was
      characterized as 3-beta-O-[alpha-L-rhamnopyranosyl(1-->4)O-beta-D
      glucopyranosyl]16-alpha-hydroxy-olean-12-en(13)-28-oic acid by several spectral
      and chemical analysis. This new triterpenoid saponin showed antimicrobial
      activity against various plants pathogenic bacteria and fungi.

PMID- 11841116
TI  - Krametosan, a new trinorlignan from the roots of Krameria tomentosa.
AB  - A new phenylcoumarone type trinorlignan, krametosan (1), along with the known
      norlignans, ratanhiaphenol I (2) and 2-(2'-hydroxy-4',6'-dimethoxyphenyl)-5-(E)
      propenylbenzofuran (3), the lignan conocarpan (4) and dinorlignan decurrenal (5),
      were isolated from the CHCl3 extract of the roots of Krameria tomentosa. The
      structure of these compounds were elucidated by the spectroscopic methods.

PMID- 11841117
TI  - A new cyclobutane lignan from Cinnamomum balansae.
AB  - A new cyclobutane lignan, named cinbalansan (6), was isolated from the leaves of
      Cinnamomum balansae, along with five known compounds, 1,2-dimethoxy-4-(1-E
      propenyl)benzene (1), 1,2-dimethoxy-4-(1-Z-propenyl)benzene (2), 1,2-dimethoxy-4
      (2-propenyl)benzene (3), 3,4-dimethoxybenzaldehyde (4), and E-(3,4
      dimethoxyphenyl)-2-propenal (5). The structure of cinbalansan was shown to be
      1beta,2beta,3alpha,4alpha-1,2-dimethyl-3,4-bis(3,4-dimethoxyphenyl)cyclobutane by
      a combination of 1H-, 13C-NMR, and NOE- experiments and by direct analysis of the
      1H-NMR spectrum by the method of X-application.

PMID- 11841118
TI  - A new oleanane triterpenoid from Gordonia ceylanica.
AB  - The chemical investigation of the hexane extract of the stem bark of Gordonia
      ceylanica afforded 3beta-acetoxy-11alpha(2',3'-epoxyferulyloxy)-olean-13(18)-ene
      as a new natural product and alpha-spinasterol for the first time from Gordonia.

PMID- 11841119
TI  - Iridoid and phenylethanoid glycosides from Phlomis longifolia var. longifolia.
AB  - From the aerial parts of Phlomis longifolia var. longifolia four iridoid
      glucosides, shanzhiside methyl ester (1), 5-deoxypulchelloside I (2), lamalbide
      (3), phlomiol (4) and three phenylethanoid glycosides, verbascoside (5),
      forsythoside B (6), leucosceptoside A (7) along with the caffeic acid ester,
      chlorogenic acid (8) were isolated. The structures of the isolated compounds were
      established by spectroscopic (UV, IR, 1D- and 2D-NMR, FABMS) and chemical
      evidence. The structure elucidation of the iridoid compounds 2 and 3 are
      discussed in detail.

PMID- 11841120
TI  - Metabolites from fungi 15. New isocoumarins from an endophytic fungus isolated
      from the Canadian thistle Cirsium arvense.
AB  - One known (1) and five new polyketide metabolites (2-6) were isolated from the
      culture extract of an endophytic fungus, Mycelia sterila, from the Canadian
      thistle Cirsium arvense. Compounds 1-4 are members of the isocoumarin family,
      whereas metabolite 5 is a dihydrobenzofuran and 6 has an open chain structure.
      All compounds have an unusual methyl group at the aromatic ring that does not fit
      into the usual polyketide pattern.

PMID- 11841121
TI  - Cycloartane triterpenes from Euphorbia tuckeyana.
AB  - Investigation of the acetone extract of the whole plant of Euphorbia tuckeyana
      afforded a new cycloartane-type triterpene named as cyclotucanol. Its structure
      was established as cycloartane-24-methylene-3beta,25-diol (1). The known
      cycloartane triterpenes cycloeucalenol (2), 3beta-hydroxycycloart-25-en-24-one
      (3), cycloart-25-ene-3beta,24-diol (4), 25,26,27-trisnor-3beta-hydroxycycloartan
      24-al (5) and cycloart-23-ene-3beta,25-diol (6) were also isolated and
      identified.

PMID- 11841123
TI  - Clinical correlates of depression following myocardial infarction.
AB  - OBJECTIVE: Post-MI depression increases mortality, especially in the first 18
      months after MI. Identifying patients at risk for post-MI depression is therefore
      important. In the present study we investigated possible correlates for post-MI
      depression on an a priori basis. METHOD: Based on the literature, four clinically
      easily attainable variables were selected as possible correlates for post-MI
      depression. These were prescription of benzodiazepines during acute
      hospitalization, cardiac complications during acute hospitalization, history of
      depression, and not being able to stop smoking within six months after MI. A
      consecutive cohort of 173 first-MI patients was screened with the SCL-90
      depression scale and DSM-III-R criteria for major depression. Of this cohort 35
      depressed patients were compared with 35 non-depressed post-MI patients, matched
      for gender, age, and severity of MI. RESULTS: In univariate analyses,
      complications during hospitalisation (OR = 2.14; CI = 0.89-5.14), prescription of
      benzodiazepines (OR = 3.67; CI = 1.11-12.1), history of depression (OR = 3.0; CI
      = 0.87-10.4), and not being able to stop smoking (OR = 4.5; CI = 1.11-18.2) were
      clinical correlates for post-MI depression. Multivariate analyses showed that
      none of these variables were independent of the others in predicting depression.
      CONCLUSIONS: A number of easily measurable patient characteristics identify those
      MI-patients at risk of post-MI depression. Further investigations should focus on
      the predictive value of these factors in relation to post-MI depression.

PMID- 11841122
TI  - Narrowing the gap in treatment of depression.
AB  - OBJECTIVE: Although effective treatments for depression exist, under or non
      treatment of depression is common. Efforts were made in the early 1990s to
      improve recognition and treatment of depression, with many of those efforts
      targeted at groups most vulnerable to under-treatment. The purpose of this study
      is to assess treatment rates in 1993-1994 and 1996-1997. METHOD: Using nationally
      representative surveys of office-based practice covering the years 1993, 1994,
      1996, and 1997, we obtained estimates of visits by adults in which depression was
      diagnosed and a prescription for antidepressant medication and/or psychotherapy
      was provided or ordered. RESULTS: The proportion of physician office visits in
      which a depression diagnosis was recorded did not change from 1993-1994 (3.48
      percent) to 1996-1997 (3.40 percent). However, the rate of antidepressant
      prescription or psychotherapy rose from 74.2 percent of visits with a depression
      diagnosis in 1993-1994 to 82.3 percent of these visits in 1996-1997.
      Significantly lower rates of treatment for depression during office visits made
      by African American patients, elderly patients, and patients on Medicaid occurred
      in 1993-1994, but were not evident in 1996-1997, reflecting improved rates of
      depression treatment in these populations. CONCLUSIONS: Although rates of
      diagnosis of depression during office visits have not increased, treatment rates
      for depression are improving among those who are diagnosed, including groups of
      people who historically were less likely to be offered treatment. Additional
      efforts to improve recognition and diagnosis of depression in ambulatory medical
      practice and to improve dissemination of treatment are needed.

PMID- 11841124
TI  - The use of an emergency ward by patients with depressive or anxiety disorders: a
      one year follow-up study.
AB  - OBJECTIVE: The present study examined patients during the year after the index
      hospitalization in an Emergency Ward (ED) to determine whether patients with
      depressive or anxiety disorders have a higher rate of readmission than patients
      without these conditions. METHOD: For this purpose, 165 subjects (85 diagnosed
      with DSM-IV depressive or anxiety disorders and 80 controls) were evaluated with
      the Hospital Anxiety and Depression Scale (HADS) and with the Duke Severity of
      Illness Scale both during the index hospitalization and one year later.
      Hospitalizations during the follow-up period were determined using the hospital
      database. RESULTS: During the follow-up period, depressed and anxious patients
      were more frequently rehospitalized in ED wards than controls (p = 0.006), after
      controlling for the effect of medical illnesses severity, marital status, living
      arrangement, and employment status. No difference was found regarding the
      admissions to wards different from ED. CONCLUSIONS: Patients with depressive or
      anxiety disorders use the ED ward more frequently than controls for the diagnosis
      and treatment of somatic symptoms.

PMID- 11841125
TI  - Methodological issues in the recruitment of primary care patients with
      depression.
AB  - OBJECTIVE: To compare two strategies of patient recruitment, waiting room (WR)
      screening and screening after physician referral (PR), for participation in a
      treatment-outcome study of minor depression and dysthymia in primary care. The
      influence of demographic factors on patients' refusal to participate in WR
      screening was also examined. METHOD: Of a convenience sample of 3,344 first stage
      patients, a total of 609 patients were evaluated in a semi-structured manner
      using a two-stage screening procedure from the mood module of the Primary Care
      Evaluation of Mental Disorders (PRIME-MD). RESULTS: Male and older patients were
      more likely to refuse participation in screening than female and younger
      patients. Waiting room screens yielded a higher number of qualified patients
      compared to PR screens, but PR screens yielded a higher percentage of patients
      who qualified for further participation. CONCLUSIONS: The recruitment of male and
      older primary care patients is complicated by their tendency to refuse
      participation in WR screening for a treatment-outcome study of milder depression.
      Although each recruitment strategy offers advantages and disadvantages, the
      simultaneous use of both is recommended to recruit the most patients in the least
      amount of time.

PMID- 11841126
TI  - Lessons learned: Outcomes and methodology of a coping skills intervention trial
      comparing individual and group formats for patients with cancer.
AB  - OBJECTIVE: Nucare, a short-term psychoeducational coping skills training
      intervention was evaluated in a randomized controlled clinical trial (RCT) of 225
      newly diagnosed breast and colon cancer patients. METHOD: Measures of
      psychosocial distress, well being and optimism were evaluated every four months
      during a one-year period. Patients were randomized to one of four arms: Nucare
      presented in an individual basis; Nucare presented in a group format; a non
      directive supportive group; and a no-intervention control. The interventions were
      provided in five sessions of ninety minutes each. RESULTS: Patients with breast
      cancer who received Nucare presented in an individual format showed more
      significant improvements in well-being over time compared to those in the control
      and group arms. CONCLUSIONS: We were unable to develop functioning groups within
      the RCT. Partial explanations for the latter finding include the structural
      limitations of the RCT: the groups were small, difficult to schedule and patients
      indicated that they would have preferred to choose whether or not to participate
      in a group. The positive changes in women with breast cancer who received Nucare
      persisted at 12 months.

PMID- 11841127
TI  - Depression, medical illness, and interleukin-1beta in older cardiac patients.
AB  - OBJECTIVE: A model has been proposed in which atherosclerosis contributes to
      depression in later life by the effects of cytokines on central monoamine
      systems. We collected pilot data to test the hypothesis that interleukin-1beta
      (IL-1beta) is associated with depression in a cardiac patient group. METHOD:
      Thirty-seven subjects completed research evaluations that included depression
      diagnosis (Structured Clinical Interview for DSM-III-R), depressive symptom
      severity (Hamilton Rating Scale for Depression), medical illness burden
      (Cumulative Illness Rating Scale), and serum IL-1beta level measured by enzyme
      linked immunosorbent assay. RESULTS: Serum IL-1beta level was not significantly
      associated with depressive symptom severity or depression diagnosis, whether or
      not controlled for medical illness burden, age, and gender. IL-1beta level was
      significantly correlated with medical illness burden. CONCLUSIONS: We did not
      confirm our study hypothesis. The correlation of IL-1beta level with medical
      illness burden likely reflects its release as part of the "sickness response" in
      a wide variety of disease states. Further research using a larger sample size and
      a non-cardiac comparison group is warranted.

PMID- 11841128
TI  - Obsessive-compulsive disorder and immunocompetence.
AB  - OBJECTIVE: A postinfectious, autoimmune response may be associated with the
      development of pediatric obsessive-compulsive disorder (OCD). According to this
      model, antistreptococcal antibodies cross-react with basal ganglia neurons
      following streptococcus infection. This autoimmune reaction disrupts a basal
      ganglia-thalamocortical circuit and generates obsessive-compulsive symptoms. One
      implication of this model is that prolonged immunologic stress may be a risk
      factor for OCD. That is, immunologic stress may compromise the blood-brain
      barrier and permit the influx of antistriatal antibodies into the central nervous
      system. This article explores one part of this putative relationship by
      investigating whether adult OCD patients, compared to members of other
      psychiatric groups, demonstrate a higher incidence of recurrent infections and
      other conditions suggestive of compromised immune function. METHOD: To test this
      hypothesis, we conducted a medical records review of 100 consecutive patients
      evaluated at a private psychiatric clinic specializing in the treatment of
      anxiety disorders. Sixty-five patients met diagnostic criteria for an Axis-I
      syndrome. Primary diagnoses included OCD, posttraumatic stress disorder, social
      anxiety disorder, generalized anxiety disorder, panic disorder with agoraphobia,
      and dysthymic disorder. Each medical record was reviewed for the presence of
      target syndromes or presenting symptoms suggestive of compromised immune
      function. RESULTS: Chart review revealed an increased rate of immune-related
      symptoms and syndromes among OCD patients in comparison to other anxiety and mood
      disorder groups. Groups did not differ significantly in the incidence of non
      immune symptoms and syndromes. CONCLUSION: Adult OCD patients appear to have an
      increased rate of immune-related diseases above and beyond that seen in other
      psychiatric disorders.

PMID- 11841129
TI  - Religion and medicine IV: religion, physical health, and clinical implications.
AB  - In the fourth and final article of this religion and medicine series, I summarize
      the results of a comprehensive and systematic review of research examining
      religion's relationship to physical health and mortality. This review focuses on
      pain and disability, cardiovascular disease, immune and neuroendocrine function,
      susceptibility to infection, cancer, and overall mortality. I also explore what
      these research findings mean for medical practice and suggest patient-centered
      applications that are sensitive to ethical concerns.

PMID- 11841130
TI  - Psychiatric complications of hydrocephalus.
AB  - This article explores the association between normal pressure hydrocephalus and
      psychiatric symptoms, such as depressed mood, delusions, and hallucinations. We
      are reporting a case of a 30-year-old female with a history of congenital
      hydrocephalus, is used to illustrate this association. Such patients may benefit
      from treatment with ventriculoperitoneal or ventriculoatrial shunt procedures.

PMID- 11841131
TI  - Schizophrenic-like symptoms in a patient with thrombo-angiitis obliterans
      (Winiwarter-Buerger's disease).
AB  - In this article a case of schizophrenic-like symptoms in a patient with thrombo
      angiitis obliterans (TAO) is presented. His CT and MRI findings indicated a
      diffuse ischemia in the white matter, suggestive of TAO, not of focal lesions.
      The patient, except for age, did not have other risk factors for other
      cerebrovascular diseases. Psychotic symptoms may be the result of cerebral TAO,
      via deep and periventricular white matter lesions.

PMID- 11841132
TI  - Rectal prolapse: a possibly underrecognized complication of anorexia nervosa
      amenable to surgical correction.
AB  - OBJECTIVE: Rectal prolapse is a complication of anorexia nervosa (AN) that may be
      more common than previously recorded experience would suggest. METHOD: In this
      report we document, for the first time, the association of (AN) and rectal
      prolapse in a series of three patients seen in the past three years. An extensive
      review of the literature using Medline over the period from 1966 to Jan 2000
      failed to reveal any previous example of this association. RESULTS AND
      CONCLUSION: The finding could have significant health care implications if
      confirmed. It would suggest that patients with either the psychiatric or surgical
      problem may not be receiving the appropriate complementary referrals:
      psychiatrist to surgeon and vice versa. The importance of recognition of this
      association in anorectic patients is the availability of effective surgical
      therapy.

PMID- 11841133
TI  - Assuring the accuracy of home glucose monitoring.
AB  - BACKGROUND: An estimated 2.5 million diabetic patients in the United States
      practice self-monitoring of blood glucose (SMBG). The validity of the glucose
      values they obtain is in doubt. An American Diabetes Association consensus panel
      reported that up to 50% of SMBG determinations might vary more than 20% from
      their true value. Accurate glucose values are an integral part of intensive
      treatment and reduction of long-term complications. The objective of this study
      was to determine the technical skill and accuracy of SMBG in an outpatient
      population. METHODS: This study was conducted in two family practice residency
      sites where 111 patients with type 1 and type 2 adult diabetes were observed
      testing their blood glucose values on their own glucose monitors. Patient
      measured glucose levels were immediately compared with a laboratory value
      obtained from a calibrated hand-held glucose monitor. RESULTS: Fifty-three
      percent of patient glucose values were within 10% of the control value, 84% were
      within 20% of the control value, and 16% varied 20% or more from the control
      value. Two patients had dangerously inaccurate glucose determinations. Four
      glucose monitors required replacement. The patients were observed using a 13
      point checklist of critical steps in calibration and operation of their glucose
      monitor. Only 1 patient made no errors in testing. CONCLUSIONS: Despite multiple
      technical errors when using SMBG, most patients obtained clinically useful
      values. This project can be easily introduced into a medical office.

PMID- 11841134
TI  - Prospective study of brief neuropsychological measures to assess crash risk in
      older primary care patients.
AB  - BACKGROUND: Practicing primary care physicians often encounter the difficult
      clinical situation of evaluating the older driver. We wanted to investigate the
      relation between self-reported driving behavior, neuropsychological measures, and
      crash risk to inform the development of a test battery that could predict unsafe
      driving behavior and was feasible for use by primary care physicians. METHODS:
      This study was a prospective follow-up of 107 drivers aged 65 years and older
      recruited from a primary care setting in 1995. Tests of attention, visual
      information processing, spatial orientation, and general mental status were
      administered at baseline. At baseline and after 2 years of follow-up, patients
      were asked about their driving history using the driving questionnaire. Risk for
      reported crashes in the follow-up period was assessed in relation to baseline
      driving history and measures of cognition. RESULTS: Baseline self-reports of
      driving habits and attitudes were associated with an increased risk of reporting
      a crash after 2 years of follow-up (relative risk ratio = 5.31; 95% confidence
      interval [CI], 0.63, 44.63). In addition, baseline tests of attention, visual
      information processing, and spatial orientation were associated with an increased
      risk of reporting motor vehicle crash at follow-up. For example, respondents with
      poor performance on the Trail Making Test-part A, were almost four times more
      likely to report a crash at follow-up (risk ratio = 3.15; 95% CI, 0.76, 13.07).
      CONCLUSION: Although our conclusions are tempered by small sample size, this
      preliminary study suggests that brief cognitive tests and simple questions about
      driving habits warrant further investigation as indicators of crash risk with
      potential utility for assessing older drivers in primary care.

PMID- 11841135
TI  - Obstetric care in family practice residencies: a 5-year follow-up survey.
AB  - BACKGROUND: The percentage of family physicians delivering babies decreased from
      46% in 1978 to 32% in 1992. Some family practice leaders predicted that, by the
      turn of the century, training for family practice obstetrics would focus
      primarily on those planning to work in remote or rural settings. A 1993 study
      found three primary factors associated with an increased incidence of future
      maternity care. In 1997 the Residency Review Commission (RRC) stipulated that all
      family practice residencies have at least 1 family physician serve as an
      intrapartum attending physician for family practice resident deliveries. METHODS:
      Using an instrument similar to that used in 1993, we surveyed the directors of
      462 family practice residencies in the United States. Sixty-four percent (295) of
      the program directors responded to one of two mailings. RESULTS: Compared with
      the survey published in 1993, program directors estimated a 16% increase in the
      number of residents who included obstetrics in their first practice after
      residency. Factors associated with increased obstetric participation included
      having only family physician faculty supervise uncomplicated deliveries and
      having family physician faculty who could perform other perinatal procedures.
      Programs that had 4 or more family physician faculty doing obstetrics and those
      that had more than 10 deliveries per month also produced more physicians who
      provided maternity care. Fifty-three percent of residencies that did not have
      family physician faculty attending deliveries before 1997 now meet this RRC
      requirement. CONCLUSIONS: This study shows that, according to their program
      directors' estimates, more family practice residents are including obstetrics in
      their first practice after residency compared with 5 years ago. The new RRC
      regulation was associated with more than 50% of previously noncompliant programs
      adding or retraining faculty who could attend resident deliveries within 12
      months of the inception of the new policy.

PMID- 11841136
TI  - Physician-patient communication in the primary care office: a systematic review.
AB  - BACKGROUND: The physician-patient interview is the key component of all health
      care, particularly of primary medical care. This review sought to evaluate
      existing primary-care-based research studies to determine which verbal and
      nonverbal behaviors on the part of the physician during the medical encounter
      have been linked in empirical studies with favorable patient outcomes. METHODS:
      We reviewed the literature from 1975 to 2000 for studies of office interactions
      between primary care physicians and patients that evaluated these interactions
      empirically using neutral observers who coded observed encounters, videotapes, or
      audiotapes. Each study was reviewed for the quality of the methods and to find
      statistically significant relations between specific physician behaviors and
      patient outcomes. In examining nonverbal behaviors, because of a paucity of
      clinical outcome studies, outcomes were expanded to include associations with
      patient characteristics or subjective ratings of the interaction by observers.
      RESULTS: We found 14 studies of verbal communication and 8 studies of nonverbal
      communication that met inclusion criteria. Verbal behaviors positively associated
      with health outcomes included empathy, reassurance and support, various patient
      centered questioning techniques, encounter length, history taking, explanations,
      both dominant and passive physician styles, positive reinforcement, humor,
      psychosocial talk, time in health education and information sharing,
      friendliness, courtesy, orienting the patient during examination, and
      summarization and clarification. Nonverbal behaviors positively associated with
      outcomes included head nodding, forward lean, direct body orientation, uncrossed
      legs and arms, arm symmetry, and less mutual gaze. CONCLUSION: Existing research
      is limited because of lack of consensus of what to measure, conflicting findings,
      and relative lack of empirical studies (especially of nonverbal behavior).
      Nonetheless, medical educators should focus on teaching and reinforcing behaviors
      known to be facilitative, and to continue to understand further how physician
      behavior can enhance favorable patient outcomes, such as understanding and
      adherence to medical regimens and overall satisfaction.

PMID- 11841137
TI  - Higher expectations for management of heart failure: current recommendations.
AB  - BACKGROUND: Some 4.6 million Americans are estimated to suffer from heart
      failure, and approximately 400,000 new cases are diagnosed each year. Each year
      260,000 patients die as a direct or indirect result of the disorder, with annual
      costs estimated between $21 billion to $40 billion. METHODS: The medical
      literature was searched using the key words "heart failure," "beta-adrenergic
      blockade," "angiotensin-converting enzyme inhibition," and "carvedilol." A case
      study illustrates the value of an emerging pharmacologic approach for some heart
      failure patients and places it in clinical perspective. RESULTS: During the past
      decade, placebo-controlled clinical trials have shown decreased morbidity and
      mortality resulting from timely intervention using a targeted multidrug approach:
      first, diuresis; then angiotensin-converting enzyme inhibition and beta
      adrenergic-receptor blockade, possibly with digoxin for symptomatic relief.
      CONCLUSIONS: An emerging approach to therapy aims to reverse the course of left
      ventricular dysfunction and arrest the underlying disease process, as well as
      improve hemodynamic function. Management of heart failure has thus entered a new
      era of more effective pharmacotherapy, often delivered within the primary care
      setting.

PMID- 11841138
TI  - Lewy body dementia: case report and discussion.
AB  - BACKGROUND: Lewy body dementia is a common but frequently underdiagnosed cause of
      dementia often mistaken for the more familiar entity of Alzheimer disease.
      Clinically the distinction is important, because it can have profound
      implications for management. METHODS: The medical literature was searched using
      the keywords "Lewy bodies," "Lewy body dementia," "Alzheimer dementia," and
      "parkinsonian disorders." A case of Lewy body dementia is described. RESULTS: An
      elderly man had long-standing diagnoses of Alzheimer disease and Parkinson
      disease. After he was evaluated thoroughly, the diagnosis was revised to Lewy
      body dementia, leading to changes in treatment that were associated with dramatic
      improvement in the patient's mental status. Evidence from the literature suggests
      that Lewy body dementia can be diagnosed in primary care settings based on
      clinical criteria. The physician should be alert to this diagnosis, and special
      attention should be paid to dementia patients who exhibit parkinsonism,
      hallucinations, fluctuating cognition, or prominent visuosperceptual deficits.
      CONCLUSIONS: The diagnosis of Lewy body dementia has important implications. It
      is associated with a high incidence of neuroleptic sensitivity, necessitating
      great caution in the use of these common antipsychotic agents. Early studies
      indicate cholinesterase inhibitors can be beneficial for treating the
      hallucinations and behavior disturbances that afflict these patients and might
      also improve cognition.

PMID- 11841139
TI  - Successful pharmacologic treatment of lower extremity ulcerations in 5 patients
      with chronic critical limb ischemia.
AB  - BACKGROUND: Ischemic ulcerations of the distal lower extremities are a
      manifestation of chronic critical limb ischemia. Without restoration of arterial
      flow, subsequent gangrene and limb loss can ensue. Unfortunately,
      revascularization is not always possible. METHODS: A literature search of MEDLINE
      was performed and a case series of 5 patients with lower extremity ischemic
      ulcerations is described. RESULTS AND CONCLUSION: Five patients with severe
      peripheral artery disease had nonhealing lower extremity ischemic ulcerations.
      Because 3 patients were not ideal candidates for percutaneous or surgical
      intervention, and 2 refused invasive therapy, they were treated with cilostazol.
      Between 7 and 24 weeks after beginning cilostazol therapy, the ulcerations healed
      in all 5 patients. Three of the patients experienced resolution of concurrent
      ischemic rest pain. One patient underwent a posttreatment noninvasive arterial
      study that documented improved large- and small-vessel perfusion. The
      antiplatelet, antithrombotic, and vasodilatory effects, in addition to possible
      unrecognized actions of cilostazol, appeared to promote wound healing in this
      small group of patients with chronic critical limb ischemia. When
      revascularization is not ideal therapy for ischemic ulcers, a pharmacologic
      approach with cilostazol might induce healing and obviate limb amputation.

PMID- 11841140
TI  - A case of SSRI-induced hyponatremia.

PMID- 11841141
TI  - Acute manic psychosis induced by triple therapy for H. pylori.

PMID- 11841142
TI  - Alprazolam-induced panic disorder.

PMID- 11841144
TI  - Family practice in Thailand: will it work?

PMID- 11841143
TI  - Determining risk between Depo-Provera use and increased uterine bleeding in obese
      and overweight women.
AB  - BACKGROUND: Millions of women worldwide use depot medroxyprogesterone acetate
      (DMPA) for contraception. Common side effects include bleeding irregularities and
      weight gain. This study examines whether a relation exists between DMPA use in
      obese and overweight women and increased uterine bleeding. METHODS: Medical
      record data were gathered retrospectively from three family medicine clinics,
      documenting weight and height, DMPA therapy, and increased or excessive bleeding.
      Body mass index was calculated for each individual and used as the identifier for
      group assignment. Comorbid conditions, such as concomitant medication use,
      history of pregnancy while on DMPA, age, socioeconomic status (determined by
      insurance source), marital status, and number of children (live births only),
      were also documented. RESULTS: An inverse association was found, indicating that
      excess weight or obesity was associated with a decreased risk of (risk ratio
      0.47) or possible protective factor against increased or excessive bleeding while
      the patient was on DMPA therapy. There was no significant outcome when
      consideration was made for age, marital status, socioeconomic status, medical
      conditions, or number of children. CONCLUSIONS: The finding that excessive weight
      or obesity was associated with a lower risk of increased or excessive bleeding
      can be advantageous when counseling this patient population on contraception
      options, especially with the knowledge that decreased side effects increase the
      propensity toward compliance and satisfaction.

PMID- 11841145
TI  - Obstetrics in family medicine: can it survive?

PMID- 11841146
TI  - Heroes lost--11 September 2001.

PMID- 11841147
TI  - Maternal smoking and congenital birth defects.

PMID- 11841148
TI  - Evaluation and management coding by family physicians.

PMID- 11841149
TI  - Association and characteristics for screening mammography.

PMID- 11841150
TI  - Restenosis after angioplasty: have we found the holy grail?

PMID- 11841151
TI  - Gender differences in arrhythmias.
AB  - Electrocardiographic and electrophysiologic differences between men and women
      have long been noted. Women have a higher intrinsic heart rate than men, along
      with a longer corrected QT interval and a shorter sinus nodal recovery time. The
      incidence of and risk factors for a variety of arrhythmias differ between men and
      women. Atrioventricular nodal reentry tachycardia has a 2:1 female-to-male
      predominance, while accessory pathways are twice as frequent in men. Although
      atrial fibrillation is more prevalent in men of all age groups, the absolute
      numbers of men and women with atrial fibrillation are equal, and the associated
      morbidity and mortality experienced by women with atrial fibrillation appear to
      be worse. Women have a lower incidence of sudden cardiac death, and female
      survivors of sudden cardiac death have a lower frequency of spontaneous or
      inducible ventricular tachycardia. On the other hand, drug-induced torsade de
      pointes and symptomatic long QT syndrome have a female predominance. Therefore,
      greater caution should be used when prescribing QT-prolonging drugs in women. The
      incidence of arrhythmias is increased during pregnancy, and management of
      pregnant patients poses a significant challenge. The mechanisms of these gender
      differences are unclear but may be related to hormonal effects and the shorter QT
      interval in adult males. Pharmacologic and nonpharmacologic therapies are usually
      equally efficacious, but the risks of pharmacologic therapy are different in men
      and women. Atrial fibrillation may be more difficult to treat in women.

PMID- 11841152
TI  - Acute myocardial infarction is associated with increased susceptibility of serum
      lipids to copper-induced peroxidation in vitro.
AB  - BACKGROUND: Low-density lipoprotein (LDL) oxidation in the arterial intima plays
      a pivotal role in atherogenesis. Under physiologic conditions, several mechanisms
      protect LDL against oxidation, including hydrolysis of oxidation products by high
      density lipoprotein (HDL)-associated enzymes. Some of these protective mechanisms
      are less effective under acute phase conditions. HYPOTHESIS: Conditions of acute
      phase response, including acute myocardial infarction (MI), may be expected to
      result in increased susceptibility of serum lipids to oxidation. The present
      study was undertaken to test this possibility. METHODS: Using our previously
      developed spectroscopic method, we have monitored prospectively the kinetics of
      copper-induced oxidation of serum lipids obtained from 15 men during and after
      acute MI. This was tested within 6 h from the onset of chest pain, on Days 1, 3,
      and 7 of infarction and 1 year after recovery. RESULTS: The lag phase preceding
      oxidation of serum lipids was much shorter during the first week after MI when
      compared with values obtained after recovery (52-59 vs. 107 min, respectively, p
      <0.001). During the first week after MI, we observed no significant correlations
      between kinetic parameters and serum lipid composition, in contrast both to the
      correlations previously reported for hyperlipidemic patients and to the similar
      correlations observed in the present study after recovery. CONCLUSIONS: Acute MI
      is associated with an increased susceptibility of serum lipids to oxidation in
      vitro. This propensity for oxidation may reflect enhanced in vivo formation of
      free radicals and/or reduced efficiency of defense mechanisms. Both these
      possibilities may carry detrimental effects on the course, complications, and
      prognosis of the patients after acute MI.

PMID- 11841154
TI  - Hypertrophic cardiomyopathy complicated by severe bradycardias: a pedigree
      report.
AB  - We describe four patients with nonobstructive hypertrophic cardiomyopathy (HCM)
      from an extended Chinese family. The patients had remarkably similar physical and
      echocardiographic findings including a harsh localized systolic murmur and apical
      left ventricular hypertrophy. All four had severe sinus bradycardia and atrial
      ventricular conduction block (AVB) manifest by recurrent syncope. Two died
      suddenly due to bradycardia. Holter monitoring showed no tachycardias. Late
      potentials were not present. We conclude that this unusual form of HCM may be
      caused by a new and as yet unknown gene mutation.

PMID- 11841153
TI  - Investigation of the predictors of transition to persistent atrial fibrillation
      in patients with paroxysmal atrial fibrillation.
AB  - BACKGROUND: Until now, no clinically useful indicators have existed that predict
      the transition from paroxysmal to persistent atrial fibrillation (AF).
      HYPOTHESIS: The current prospective study was conducted for identifying
      predictors of progression to persistent AF over the long term. METHODS: We
      studied 102 consecutive patients (mean age: 55 +/- 10 years: 75 men and 27 women)
      diagnosed with paroxysmal AF. Standard 12-lead electrocardiography,
      echocardiography, and P-wave-triggered signal-averaged electrocardiography (P
      SAECG) were performed on all patients at the time of their entry into the study.
      RESULTS: The mean follow-up period was 61 +/- 13 months. Group 1 (n = 66)
      comprised patients in whom paroxysmal AF did not progress to persistent AF, and
      Group 2 (n = 36) comprised those who developed persistent AF. In Group 2 the
      patients were significantly older, and P-wave dispersion, filtered P-wave
      duration (FPD), and left atrial dimension were significantly higher than in Group
      1 (p < 0.05). The root mean square voltage for the last 30 ms of the filtered P
      wave was also significantly lower in Group 2 (p < 0.05). Multivariate logistic
      regression analysis using these five factors identified left atrial dimension
      (odds ratio [OR] 2.29; 95% confidence interval [CI] 1.16-4.54; p = 0.02) and FPD
      (OR 2.71; 95% CI 1.78-4.13; p < 0.01) as independent predictors of transition to
      persistent AF. Left atrial dimension > or = 40 mm predicted progression to
      persistent AF with a sensitivity of 64%, specificity of 76%, positive predictive
      value of 59%, negative predictive value of 79%, and an accuracy of 71%. An FPD >
      or = 150 ms predicted persistent AF with a sensitivity of 81%, specificity of
      91%, positive predictive value of 88%, negative predictive value of 90%, and an
      accuracy of 87%. Filtered P-wave duration was a significantly more sensitive and
      specific predictor than left atrial dimension (p < 0.05). CONCLUSION: We conclude
      that FPD is a clinically useful predictor of progression from paroxysmal to
      persistent AF over the long term.

PMID- 11841155
TI  - Double saphenous vein graft patency 23 years following coronary artery bypass
      surgery.

PMID- 11841156
TI  - Primary pericardial fibrosarcoma presenting as "near" cardiac tamponade.
AB  - A 19-year-old male presented with fever, substernal pain, dyspnea, and distended
      neck veins. Diagnostic investigations, such as echocardiography and magnetic
      resonance imaging, provided evidence of a large mass within the pericardial sac,
      attached by a broad base to the parietal pericardium and lying along the right
      ventricular free wall. A partial pericardiectomy was performed to relieve the
      patient's symptoms, and histologic examination of a biopsy specimen showed
      features of a malignant, spindle cell, mesenchymal neoplasm. The patient
      underwent surgical treatment during which the tumor was found to infiltrate the
      anterior surface of the right ventricle. Histologically, the tumor was identified
      as a high-grade fibrosarcoma, and additional chemotherapy was given.

PMID- 11841157
TI  - Dennis Michael Krikler.

PMID- 11841158
TI  - Variability of genetic sex determination in poeciliid fishes.
AB  - Poeciliids are one of the best-studied groups of fishes with respect to sex
      determination. They present an amazing variety of mechanisms, which span from
      simple XX-XY or ZZ-ZW systems to polyfactorial sex determination. The gonosomes
      of poeciliids generally are homomorphic, but very early stages of sex chromosome
      differentiation have been occasionally detected in some species. In the platyfish
      Xiphophorus maculatus, gene loci involved in melanoma formation, in different
      pigmentation patterns and in sexual maturity are closely linked to the sex
      determining locus in the subtelomeric region of the X- and Y- chromosomes. The
      majority of traits encoded by these loci are highly polymorphic. This phenomenon
      might be explained by the high level of genomic plasticity apparently affecting
      the sex-determining region, where frequent rearrangements such as duplications,
      deletions, amplifications, and transpositions frequently occur. We propose that
      the high plasticity of the sex-determining region might explain the variability
      of sex determination in Xiphophorus and other poeciliids.

PMID- 11841160
TI  - Chromosome painting supports lack of homology among sex chromosomes in
      Oncorhynchus, Salmo, and Salvelinus (Salmonidae).
AB  - The sex chromosome pair has been identified previously as the largest
      submetacentric pair in the genome in several species of the genus Salvelinus
      (eastern trouts and chars) including S. namaycush (lake trout) and as a large
      subtelocentric/acrocentric pair in several species of the genus Oncorhynchus
      (Pacific trouts and salmon). Sex chromosomes have not been identified in Salmo
      (Atlantic salmon and brown trout). Two paint probes, one specific for the short
      arm (Yp) and the other for the long arm (Yq) of the sex chromosome pair in
      Salvelinus namaycush were hybridized to chromosomes of Oncorhynchus mykiss
      (rainbow trout) and O. tshawytscha (chinook salmon) and Salmo salar (Atlantic
      salmon) and S. trutta (brown trout). The two probes hybridized to two different
      autosomal pairs in each of the Oncorhynchus species, supporting lack of homology
      between the sex chromosomes in the two genera. The Yp probe hybridized to
      interstitial regions on two different chromosome pairs in S. salar and one pair
      in S. trutta. The Yq probe hybridized to a different pair in both species.

PMID- 11841159
TI  - Sex identification by male-specific growth hormone pseudogene (GH-psi) in
      Oncorhynchus masou complex and a related hybrid.
AB  - It is often difficult to identify sexes of many fish species by conventional
      cytological method because of the lack of heteromorphic sex chromosomes.
      Isolation of sex-specific molecular markers is thus important for sexing and for
      understanding sex chromosome evolution in these species. We have identified
      genetic sexes by PCR-based male-specificity of a growth hormone pseudogene (GH
      psi) in masu and Biwa salmon, two subspecies of the Oncorhynchus masou complex,
      and their hybrid Honmasu. PCRs with primers designed from sequences of chinook
      salmon GH genes amplified GH-I and GH-II fragments in both sexes, but a third GH
      psi fragment was detected in predominant proportion of males and very few
      phenotypic females. The consistency of phenotypic sex with genetic sex identified
      by GH-psi for masu salmon, Biwa salmon and Honmasu was 93.1, 96.7 and 94%,
      respectively. The remaining individuals showed inconsistency or deviation from
      sex-specificity: a few phenotypic males lacked the GH-psi, whereas a few
      phenotypic females possessed the GH-psi. Sequence of the putative GH-psi fragment
      from such females was identical to that from genetic males, and shared about 95%
      homology with the corresponding GH-psi fragment from chinook salmon. This result
      confirmed that these females were really GH-psi-bearing individuals. PCR analyses
      with primers designed from masu salmon GH-psi gave identical results, indicating
      that the absence of GH-psi in a few males was not resulted from primer
      mismatching. These GH-psi-bearing females and GH-psi-absent males were more
      likely to originate from spontaneous sex reversion than from crossing-over
      between GH-psi and the sex determination gene/region.

PMID- 11841162
TI  - Heteromorphic sex chromosomes of lizardfish (Synodontidae): focus on the ZZ-ZW1W2
      system in Trachinocephalus myops.
AB  - The karyotype and DNA content of four lizardfish species (family Synodontidae),
      that is, Saurida elongata, Synodus ulae, Synodus hoshinonis and Trachinocephalus
      myops, were analyzed. The karyotype of T. myops significantly differed from that
      of the other three species having diploid chromosome number of 48 with mainly
      acrocentric chromosomes and the ZZ-ZW sex chromosome system. The chromosome
      number of male T. myops was 2n = 26, while that of female T. myops was 2n = 27.
      The karyotype consisted of 11 pairs of metacentrics, one pair of acrocentrics
      and, in addition, two large metacentrics in the male and a single large
      metacentric, a distinctly small subtelocentric and a microchromosome in the
      female. C-banding demonstrated that in the female the subtelocentric chromosome
      and the microchromosome were heterochromatic. The karyotype of T. myops was
      thought to be derived from a 48 chromosome type synodontid fish through the
      involvement of Robertsonian rearrangement; the rearrangement of the sex
      chromosomes proceeded during karyotype evolution. Among the chromosomes, the
      large metacentrics were determined to be neo-Z (a fusion of the original Z and an
      autosome), the microchromosomes the W1 (originally W), and the subtelocentric
      chromosomes the W2 (derived from an autosome pair). The miniaturization of W1 and
      W2 chromosomes and their heterochromatinization suggested that sex chromosomes in
      this species have been already highly differentiated. The findings on DNA content
      implied that the karyotype of T. myops evolved by centric fusion events without
      loss in DNA amount.

PMID- 11841161
TI  - Characterization of sex chromosomes in rainbow trout and coho salmon using
      fluorescence in situ hybridization (FISH).
AB  - With the aim of characterizing the sex chromosomes of rainbow trout (Oncorhynchus
      mykiss) and to identify the sex chromosomes of coho salmon (O. kisutch), we used
      molecular markers OmyP9, 5S rDNA, and a growth hormone gene fragment (GH2), as
      FISH probes. Metaphase chromosomes were obtained from lymphocyte cultures from
      farm specimens of rainbow trout and coho salmon. Rainbow trout sex marker OmyP9
      hybridizes on the sex chromosomes of rainbow trout, while in coho salmon,
      fluorescent signals were localized in the medial region of the long arm of one
      subtelocentric chromosome pair. This hybridization pattern together with the
      hybridization of a GH2 intron probe on a chromosome pair having the same
      morphology, suggests that a subtelocentric pair could be the sex chromosomes in
      this species. We confirm that in rainbow trout, one of the two loci for 5S rDNA
      genes is on the X chromosome. In males of this species that lack a heteromorphic
      sex pair (XX males), the 5S rDNA probe hybridized to both subtelocentrics. This
      finding is discussed in relation to the hypothesis of intraspecific polymorphism
      of sex chromosomes in rainbow trout.

PMID- 11841163
TI  - Identification of putative sex chromosomes in the blue tilapia, Oreochromis
      aureus, through synaptonemal complex and FISH analysis.
AB  - Sex determination in the blue tilapia, Oreochromis aureus, is primarily a ZW
      female-ZZ male system. Here, by analysis of the pachytene meiotic chromosomes of
      O. aureus, we demonstrate the presence of two distinct regions of restricted
      pairing present only in heterogametic fish. The first, a subterminal region of
      the largest bivalent is located near to the region of unpairing found in the
      closely related species O. niloticus, while the second is in a small bivalent,
      most of which was unpaired. These results suggest that O. aureus has two separate
      pairs of sex chromosomes.

PMID- 11841164
TI  - Genetic manipulations in aquaculture: a review of stock improvement by classical
      and modern technologies.
AB  - The aim of this review was to highlight the extent to which the genetic
      technologies are implemented by the aquaculture industry. The review shows that
      some of the modern genetic technologies are already extensively applied by the
      diverse aquaculture industries, though not to the same extent for all important
      aquacultured species (according to FAO 1998 figures). Some species (common carp,
      Atlantic salmon, rainbow trout, channel catfish, Nile tilapia, and the Pacific
      oyster) received concentrated breeding efforts, while other major cultured
      species (Chinese and Indian carps and the giant tiger shrimp) received, so far,
      relatively limited attention, and a few species (Yesso scallop, blue mussel,
      white Amur bream, and milkfish) have, apparently, not been genetically improved
      at all. Most of the genetically improved strains reaching the aquaculture
      industry were developed through traditional selective breeding (selection,
      crossbreeding, and hybridization). Emerging, more modern technologies for genetic
      manipulation seem to take 10-20 years from being established experimentally until
      applications affect the industry. Thus, chromosome-set and sex manipulations
      started to affect the industry during the 1980's and 1990's. DNA marker
      technology and gene manipulations have yet hardly affected the industry. The
      former have not matured yet, but hold much promise. The latter could have
      affected the industry already had it not been restricted by public concern.

PMID- 11841165
TI  - Induction of triploidy and gynogenesis in teleost fish with emphasis on marine
      species.
AB  - The induction of triploidy and gynogenesis by chromosome set manipulation has
      traditionally been studied more intensively in freshwater than in marine fish. In
      the last years, however, several studies have applied these manipulations in
      about a dozen marine species, including mainly sparids, moronids and flatfishes.
      This paper focuses on the methodologies used to induce, verify, and assess
      performance of both triploids and gynogenetics of these marine species. Since
      many of them are batch spawners and have small and fragile eggs and larvae,
      peculiarities relating to broodstock management, gamete quality and mortality
      assessment during early larval stages are also taken into account. However, data
      show that if handling is correct and the treatments are optimized, triploid and
      gynogenetic rates of 100% can be easily achieved. Survival of triploids with
      respect to the controls is about 70-80%, whereas in gynogenetics it is generally
      low and more variable, depending on the species considered. In the marine fish
      investigated so far, triploidy has not resulted in significantly higher growth
      rates. On the other hand, the induction of gynogenesis has resulted in the
      production of both all-female and mix-sex stocks. Throughout the paper, special
      reference is made to the European sea bass (Dicentrarchus labrax L.), a species
      of both basic and applied interest, for which a comprehensive study has been
      carried out on the induction, verification and performance of triploids and
      gynogenetics.

PMID- 11841166
TI  - Ocean migration and recaptures of tagged, triploid, mixed-sex and all-female
      Atlantic salmon (Salmo salar L.) released from rivers in Ireland.
AB  - Fiftyfour thousand diploid and triploid Atlantic salmon were tagged with coded
      wire micro-tags and released to the sea as smolts from two freshwater sites in
      Ireland in 1996 and 1997. Over 36,000 were mixed-sex groups in which the
      triploids (MS3N) were treated batches and the diploids (MS2N) were untreated
      batches of a single group of fertilized eggs at each site and year class. Over
      17,000 were all-females, the triploids (AF3N) being treated batches and the
      diploids (AF2N) untreated batches of a single group of fertilized eggs at each
      site and year class. Adult tagged fish were subsequently recovered in the coastal
      fishery and in freshwater traps and angling fisheries in the rivers of release
      during 1997, 1998 and 1999. Recoveries from migration ranged from 0.08 to 9.79%.
      Diploid recoveries were within the normal ranges for salmon ranched from these
      sites, being between 0.64 and 1.82% at one site and between 3.85 and 9.79% at the
      other. Triploid recoveries, which occurred in the coastal fishery and in
      freshwater, ranged from 0.08 to 0.40% at the first site and from 0.98 to 2.05% at
      the other. Overall, triploid recoveries were between 12 and 24% of their diploid
      siblings within each release group. There were two peaks of recapture in the
      coastal fishery, the first in mid-June and the second in mid to late July. All
      female diploids appeared to enter the fishery in advance of mixed-sex diploids.
      Triploids were the latest to arrive. There was no evidence of increased straying
      in triploids relative to diploids and the mean lengths, weights and condition
      factors were not significantly different between the ploidy groups.
      Triploidisation therefore reduced the home water harvest of treated salmon to
      less than 25% but did not completely eliminate triploid recaptures. The way in
      which triploidisation may influence the return of salmon from the oceanic feeding
      grounds is discussed.

PMID- 11841168
TI  - Germ-line chimera by lower-part blastoderm transplantation between diploid
      goldfish and triploid crucian carp.
AB  - Germ-line chimerism was successfully induced by blastoderm transplantation from
      donor triploid crucian carp, which reproduces gynogenetically, to recipient
      diploid goldfish, which reproduces bisexually. Lower part of donor blastoderm
      including primordial germ cells (PGCs) was sandwiched between recipient
      blastoderm at the mid- to late-blastula stage. When donor grafts were prepared
      from intact embryos or ventralized ones by removing vegetal yolk hemisphere at
      the 1- to 2-cell stage, malformations including double axes were observed in the
      resultant chimeras transplanted with grafts from intact embryos at the hatching
      stage, while a few malformations in those from ventralized embryos. PGCs
      originated from donor grafts were observed around the gonadal anlage at 10 days
      post-fertilization in chimeras. When ploidy of erythrocytes and epidermal cells
      in chimeric fish was examined by flow-cytometry, no triploid cells were detected
      at 1- and 5-year-old chimeras. Three-year-old chimeric fish (n = 5) laid eggs
      originated from the donor together with those from the recipient. The frequency
      of eggs from the donor crucian carp blastoderm varied from 3.1 to 89.3% between
      chimeras.

PMID- 11841167
TI  - Green fluorescent protein (GFP) transgenic fish and their applications.
AB  - The coupling of the GFP reporter system with the optical clarity of embryogenesis
      in model fish such as zebrafish and medaka is beginning to change the picture of
      transgenic fish study. Since the advent of first GFP transgenic fish in 1995, GFP
      transgenic fish technology have been quickly employed in many areas such as
      analyses of gene expression patterns and tissue/organ development, dissection of
      promoters/enhancers, cell lineage and axonal pathfinding, cellular localization
      of protein products, chimeric embryo and nuclear transplantation, cell sorting,
      etc. The GFP transgenic fish also have the potentials in analysis of upstream
      regulatory factors, mutagenesis screening and characterization, and
      promoter/enhancer trap. Our own studies indicate that GFP transgenic fish may
      become a new source of novel variety of ornamental fish. Efforts are also being
      made in our laboratory to turn GFP transgenic fish into biomonitoring organisms
      for surveillance of environmental pollution.

PMID- 11841169
TI  - Geographic heterogeneity in natural selection on an MHC locus in sockeye salmon.
AB  - Balancing selection maintains high levels of polymorphism and heterozygosity in
      genes of the MHC (major histocompatibility complex) of vertebrate organisms, and
      promotes long evolutionary persistence of individual alleles and strongly
      differentiated allelic lineages. In this study, genetic variation at the MHC
      class II DAB-beta1 locus was examined in 31 populations of sockeye salmon
      (Oncorhynchus nerka) inhabiting the Fraser River drainage of British Columbia,
      Canada. Twenty-five percent of variation at the locus was partitioned among
      sockeye populations, as compared with 5% at neutral genetic markers. Geographic
      heterogeneity of balancing selection was detected among four regions in the
      Fraser River drainage and among lake systems within regions. High levels of beta1
      allelic diversity and heterozygosity, as well as distributions of alleles and
      allelic lineages that were more even than expected for a neutral locus, indicated
      the presence of balancing selection in populations throughout much of the
      interior Fraser drainage. However, proximate populations in the upper Fraser
      region, and four of six populations from the lower Fraser drainage, exhibited
      much lower levels of genetic diversity and had beta1 allele frequency
      distributions in conformance with those expected for a neutral locus, or a locus
      under directional selection. Pair-wise FST values for beta1 averaged 0.19 and
      tended to exceed the corresponding values estimated for neutral loci at all
      levels of population structure, although they were lower among populations
      experiencing balancing selection than among other populations. The apparent
      heterogeneity in selection resulted in strong genetic differentiation between
      geographically proximate populations with and without detectable levels of
      balancing selection, in stark contrast to observations at neutral loci. The
      strong partitioning and complex structure of beta1 diversity within and among
      sockeye populations on a small geographic scale illustrates the value of
      incorporating adaptive variation into conservation planning for the species.

PMID- 11841170
TI  - Combining the analyses of introgressive hybridisation and linkage mapping to
      investigate the genetic architecture of population divergence in the lake
      whitefish (Coregonus clupeaformis, Mitchill).
AB  - Adaptation and reproductive isolation, the engines of biological diversity, are
      still elusive when discussing the genetic bases of speciation. Namely, the number
      of genes and magnitude of selection acting positively or negatively on genomic
      traits implicated in speciation is contentious. Here, we describe the first steps
      of an ongoing research program aimed at understanding the genetic bases of
      population divergence and reproductive isolation in the lake whitefish (Coregonus
      clupeaformis). A preliminary linkage map originating from a hybrid cross between
      dwarf and normal ecotypes is presented, whereby some of the segregating AFLP
      markers were found to be conserved among natural populations. Maximum-likelihood
      was used to estimate hybrid indices from non-diagnostic markers at 998 AFLP loci.
      This allowed identification of the most likely candidate loci that have been
      under the influence of selection during the natural hybridisation of whitefish
      originating from different glacial races. As some of these loci could be
      identified on the linkage map, the possibility that selection of traits in
      natural populations may eventually be correlated to specific chromosomal regions
      was demonstrated. The future prospects and potential of these approaches to
      elucidate the genetic bases of adaptation and reproductive isolation among
      sympatric ecotypes of lake whitefish is discussed.

PMID- 11841171
TI  - Use of a genetic marker to examine genetic interaction among subpopulations of
      pink salmon (Oncorhynchus gorbuscha).
AB  - In 1979 and 1981, a genetic marker was bred into one of the five identifiable
      subpopulations of pink salmon [Oncorhynchus gorbuscha (Walbaum)] in the Auke Lake
      drainage in Southeast Alaska. As a result of the marking effort, the frequencies
      of two malate dehydrogenase (MDH-B1, 2*) alleles were changed in the marked
      subpopulation, but not in other subpopulations that spawn at different times or
      places. Between 1983 and 1989, the marker allele frequencies were monitored in
      many of these subpopulations and in early- and late-run pink salmon spawning in
      nearby Waydelich Creek, located approximately 1 km away. Changes in allele
      frequencies at MDH-B1, 2*, used to obtain direct estimates of average migration
      rates (m) from the marked to the unmarked subpopulations, revealed little or no
      introgression into early subpopulations or into nearby Waydelich Creek. Moreover,
      spatially distinct late-run Auke Creek subpopulations were not immediately
      overrun by the more abundant marked subpopulation. These observations suggest
      that genetic isolation exists between temporally distinct spawning runs and that
      small temporal and spatial (or ecological) differences contribute to population
      structure. These observations should be considered in taking actions that affect
      conservation and harvest management or extensive culture of salmonids.

PMID- 11841172
TI  - Microsatellite analyses of the trout of northwest Mexico.
AB  - The trout of northwest Mexico represent an undescribed group of fish considered
      part of the Oncorhynchus mykiss (Pacific trout) complex of species and
      subspecies. Recent genetic studies have shown these fish to have important
      genetic diversity and a unique evolutionary history when compared to coastal
      rainbow trout. Increased levels of allelic diversity have been found in this
      species at the southern extent of its range. In this study we describe the trout
      in the Sierra Madre Occidental from the rios Yaqui, Mayo, Casas Grandes and de
      Bavispe, and their relationship to the more southern distribution of Mexican
      golden trout (O. chrysogaster) using 11 microsatellite loci. Microsatellite
      allelic diversity in Mexican trout was high with a mean of 6.6 alleles/locus,
      average heterozygosity = 0.35, and a mean Fst = 0.43 for all loci combined.
      Microsatellite data were congruent with previously published mtDNA results
      showing unique panmictic population structure in the Rio Yaqui trout that differs
      from Pacific coastal trout and Mexican golden trout. These data also add support
      for the theory of headwaters transfer of trout across the Continental Divide from
      tributaries of the Rio de Bavispe into the Rio Casas Grandes. Rio Mayo trout
      share a close genetic relationship to trout in Rio Yaqui, but sample sizes from
      the Rio Mayo prevent significant comparisons in this study. Microsatellite
      analyses show significant allelic frequency differences between Rio Yaqui trout
      and O. chrysogaster in Sinaloa and Durango Mexico, adding further support for a
      unique evolutionary status for this group of northwestern Mexican trout.

PMID- 11841173
TI  - Genetics of the guppy as a model for experiment in aquaculture.
AB  - The guppy, Poecilia reticulata, is one of the most famous tropical ornamental
      fish in the world. There are many varieties and breeds which have been bred by
      aqua lists for many years. The guppy has frequently been used as model organism
      for experiments in fish genetics because of its short life cycle, ease of
      breeding and reproductive capacity. The laboratory strains which were created
      from local (Japanese) strains and varieties were used as an experimental genetic
      model for aquaculture. These laboratory strains were maintained as closed
      colonies for five to 20 years in our laboratory. One of the roles of model
      experiments in fish genetics to perform experiments which take a long time in
      which are commercially important, such as genetic drift, as the effect of
      inbreeding during the growth and maintenance of population. In this review, we
      mainly considered the results obtained in our laboratory relating to genetic
      drift, and the effects of inbreeding, heterosis and inheritance of quantitative
      traits.

PMID- 11841174
TI  - Selective recovery of founder genetic diversity in aquacultural broodstocks and
      captive, endangered fish populations.
AB  - Hatchery broodstocks used for genetic conservation or aquaculture may represent
      their ancestral gene pools rather poorly. This is especially likely when the fish
      that found a broodstock are close relatives of each other. We re-analysed
      microsatellite data from a breeding experiment on red sea bream to demonstrate
      how lost genetic variation might be recovered when gene frequencies have been
      distorted by consanguineous founders in a hatchery. A minimal-kinship criterion
      based on a relatedness estimator was used to select subsets of breeders which
      represented the maximum number of founder lineages (i.e., carried the fewest
      identical copies of ancestral genes). UPGMA clustering of Nei's genetic distances
      grouped these selected subsets with the parental gene pool, rather than with the
      entire, highly 'drifted' offspring generation. The selected subsets also captured
      much of the expected heterozygosity and allelic diversity of the parental gene
      pool. Independent pedigree data on the same fish showed that the selected subsets
      had more contributing parents and more founder equivalents than random subsets of
      the same size. The estimated mean coancestry was lower in the selected subsets,
      meaning that inbreeding in subsequent generations would be lower if they were
      used as breeders. The procedure appears suitable for reducing the genetic
      distortion due to consanguineous and over-represented founders of a hatchery gene
      pool.

PMID- 11841175
TI  - Gene mapping in fishes: a means to an end.
AB  - Genetic research in fishes is poised to contribute a vast amount of information
      on the structural organization and function of vertebrate genomes. Recent
      advances in molecular biology have made possible the widescale characterization
      of genomes in all living organisms. This includes defining chromosomes at the
      cytological level down to their linear composition at individual nucleotide base
      pairs. Pioneering gene mapping studies into the genomes of fishes will only serve
      as the starting point for more detailed studies into the function of these
      genomes. Future research directed at understanding the mechanisms of gene actions
      and interactions will benefit all areas of biology, including ecology, ethology,
      evolution, and physiology. Gene mapping data from brown trout and rainbow trout
      are used to exemplify how basic information on gene transmission in a species may
      help to localize centromeres onto a genetic map and identify chromosomal regions
      possessing a high degree of segregation distortion. Genetic maps may also be used
      to identify differences in recombination levels among individuals and between the
      sexes when multiple mapping families are utilized in studies. Observations of
      this type are the antecedents to more complex biological investigations on the
      genetic architecture underlying these phenomena.

PMID- 11841176
TI  - A modified stepping-stone model of population structure in red drum, Sciaenops
      ocellatus (Sciaenidae), from the northern Gulf of Mexico.
AB  - Genetic studies of population or 'stock' structure in exploited marine fishes
      typically are designed to determine whether geographic boundaries useful for
      conservation and management planning are identifiable. Implicit in many such
      studies is the notion that subpopulations or stocks, if they exist, have fixed
      territories with little or no gene exchange between them. Herein, we review our
      long-term genetic studies of red drum (Sciaenops ocellatus), an estuarine
      dependent sciaenid fish in the Gulf of Mexico and western Atlantic Ocean.
      Significant differences in frequencies of mitochondrial DNA haplotypes and of
      alleles at nuclear-encoded microsatellites occur among red drum sampled across
      the northern Gulf of Mexico. The spatial distribution of the genetic variation,
      however, follows a pattern of isolation-by-distance consistent with the
      hypothesis that gene flow occurs among subpopulations and is an inverse (and
      continuous) function of geographic distance. However, successful reproduction and
      recruitment of red drum depend on estuarine habitats that have geographically
      discrete boundaries. We hypothesize that population structure in red drum follows
      a modified one-dimensional, linear stepping-stone model where gene exchange
      occurs primarily (but not exclusively) between adjacent bays and estuaries
      distributed linearly along the coastline. Gene flow does occur among estuaries
      that are not adjacent but probabilities of gene exchange decrease as a function
      of geographic distance. Implications of our hypothesis are discussed in terms of
      inferences drawn from patterns of isolation-by-distance and relative to
      conservation and management of estuarine-dependent species like red drum. Based
      on estimates of the ratio of genetic effective population size and census size in
      red drum, observed patterns of gene flow in red drum may play a significant role
      in recruitment.

PMID- 11841177
TI  - Highly repetitive DNA families restricted to germ cells in a Japanese hagfish
      (Eptatretus burgeri): a hierarchical and mosaic structure in eliminated
      chromosomes.
AB  - It is known that in eight hagfishes chromosome elimination occurs during early
      embryogenesis. The eliminated chromosomes are mostly C-band positive, so that
      none of the somatic cells have any C-band-positive chromatin. Recently, some
      highly repetitive DNA sequences have been reported as eliminated elements in
      these hagfishes based on molecular biological methods. However, no germline
      restricted repetitive DNA have been directly isolated from the Japanese hagfish
      Eptatretus burgeri, from which approximately 21% of the total DNA is eliminated
      from presumptive somatic cells. Through electrophoretic investigation after
      digestion with restriction endonucleases, two DNA families that are restricted to
      germline DNA were isolated. Molecular cloning and sequence analysis revealed that
      these families are composed of closely related sequences of 64 and 57bp in
      length, respectively. Southern blot hybridization revealed that the two DNA
      families are restricted to germline DNA and were thus named EEEb1 and EEEb2,
      respectively. Moreover, these eliminated elements were highly and tandemly
      repeated, and it is predicted that they might amplify by saltatory replication
      and have evolved in a concerted manner. By densitometric scanning, EEEb1 and
      EEEb2 were found to amount to make up approximately 18.5 and 0.024% of the total
      germline genomic DNA, accounting for 88.6% of the total eliminated DNA. A
      fluorescence in situ hybridization experiment demonstrated that EEEb1 is located
      on all C-band-positive chromosomes that are limited to germ cells, suggesting
      that EEEb1 is the primary component of eliminated DNA of E. burgeri.

PMID- 11841178
TI  - Selachian cytogenetics: a review.
AB  - The karyotype of Chondrichthyes is still the least investigated among
      vertebrates. Over the last 40 years, the karyotypes of 63 out of the 1100 known
      species (5.73%) have been described in literature, namely seven squalomorph, one
      squatinomorph, 20 galeomorph, 33 batoid and two holocephalian species. Generally,
      the diploid number ranges from a minimum of 28 to a maximum of 106 elements, with
      more frequent values observed between 50 and 100 chromosomes. None of the four
      superorders is characterized by a peculiar chromosome set or morphology; the
      number of uniarmed and biarmed elements is variable in all the karyotypes, and
      microchromosomes are often present. The general trend in all groups seems to be a
      progressive reduction of the telocentric chromosome number in the most
      specialized species, followed by the loss of the microchromosomes. Polyploidy,
      followed by diploidization events and Robertsonian rearrangements, might have
      played a key role in the karyological evolution of elasmobranch fish.
      Chondrichthyes have the largest genome sizes among vertebrates, with the
      exception of dipnoans and urodeles. In the whole class, the species examined vary
      greatly in size, from 3 to 34pg/N: the lowest values have been observed in
      holocephalians, while galeoids and batoids have a DNA amount ranging from 5 to 15
      pg/N. Squaloids show heterogeneous DNA amounts, ranging from 8 to 34 pg/N. In
      more recent years, karyological studies have provided new data on the
      characterization of selachian karyotypes by C-banding, NOR staining, restriction
      enzymes in situ digestion and FISH with specific DNA probes, such as telomeric
      and SINE sequences.

PMID- 11841179
TI  - The phylogenetic placement of chondrichthyes: inferences from analysis of
      multiple genes and implications for comparative studies.
AB  - Elasmobranch fishes (sharks and rays) have proven valuable for inferring general
      and specific properties of molecular evolution through comparative studies with
      crown group vertebrates because they are the most ancient group of gnathostomes.
      Recent studies have questioned the conventional phylogenetic placement of sharks
      in the vertebrate tree, however. In this paper I review the importance of the
      basal position of Chondrichthyes for comparative biology and compile evidence
      from multiple, independent genes to evaluate the phylogenetic placement of
      sharks. The results suggests that alternative phylogenetic hypotheses of the
      relationships among the Chondrichthyes, Actinopterygii and Sarcopterygii can not
      be refuted with available data, implying that the assumption of the basal
      placement of sharks in the vertebrate tree is suspect. Resolving the phylogeny of
      basal vertebrates is important for testing hypotheses about the evolution of
      vertebrates, and the current lack of a robust phylogeny limits evolutionary
      inferences that can be gained from comparative studies that include sharks and
      rays.

PMID- 11841180
TI  - Sturgeon genetics and cytogenetics: recent advancements and perspectives.
AB  - The aim of this review is to introduce current knowledge in the field of sturgeon
      genetics. The first section deals with sturgeon cytogenetics, reviewing karyotype
      organization and polyploidization events during evolution of Acipenseriformes.
      The second section concerns the results of applications of molecular biology to
      studies of phylogenetic relationships between extant species, intraspecific
      analysis of wild populations and stocks for conservation purposes, together with
      characterization of molecular markers for species identification, relevant to
      forensic and conservation issues.

PMID- 11841182
TI  - Comparative chromosomal studies on two minnow fish, Phoxinus phoxinus (Linnaeus,
      1758) and Eupallasella perenurus (Pallas, 1814); an associated cytogenetic
      taxonomic considerations.
AB  - The present work provides new data on the banding pattern of two cyprinid fish
      species Phoxinus phoxinus and Eupallasella perenurus from Poland. C-banding,
      silver-staining (Ag), and fluorescent staining with chromomycin A3 techniques
      were used to describe the karyotypes. Both of the species karyotypes of 2n = 50
      were characterised by one pair of acrocentric chromosomes, the largest in the
      set, and by two pairs of NOR-bearing chromosomes. In the chromosome set of Ph.
      phoxinus Ag-stained NORs were located on telomeres of two metacentric and two
      submetacentric chromosomes, but in most metaphases only one of the two homologous
      was observed. The karyotype of E. perenurus was characterised by Ag-NOR regions
      at a telomeric position on the shorter arm of two submetacentric chromosome
      pairs. In most metaphases only three NOR-bearing chromosomes were observed. In
      both investigated species the location of the A3 positive signals corresponded
      with the location of Ag-stained NORs and these sites were associated with
      heterochromatin shown as C-bands. The results of cytogenetical studies on other
      related, mainly the North American phoxinins, species are compared and discussed.

PMID- 11841181
TI  - Evolution in action through hybridisation and polyploidy in an Iberian freshwater
      fish: a genetic review.
AB  - The Iberian minnow Leuciscus alburnoides represents a complex of diploid and
      polyploid forms with altered modes of reproduction. In the present paper, we
      review the recent data on the origin, reproductive modes, and inter-relationships
      of the various forms of the complex, in order to predict its evolutionary
      potential. The complex follows the hybrid-origin model suggested for most other
      asexual vertebrates. Diploid and triploid females from the southern river basins
      exhibit reproductive modes that cannot be conveniently placed into the categories
      generally recognised for these vertebrate complexes, which imply continuous
      shifting between forms, where genomes derived from both parental ancestors are
      cyclically lost, gained or replaced. Replacement of nuclear genomes allow the
      introduction of novel genetic material, that may compensate for the disadvantages
      of asexual reproduction. Contrasting with most other vertebrate complexes, L.
      alburnoides males are fertile and play an important role in the dynamics of the
      complex. Moreover, diploid hybrid males may have initiated a tetraploidization
      process, when a diploid clonal sperm fertilised a diploid egg. This direct route
      to tetraploidy by originating fish with the right constitution for normal meiosis
      (symmetric), may eventually lead to a new sexually reproducing polyploid species.
      This case-study reinforces the significance of hybridisation and polyploidy in
      evolution and diversification of vertebrates.

PMID- 11841183
TI  - Classical and molecular cytogenetics of the zebrafish, Danio rerio (Cyprinidae,
      Cypriniformes): an overview.
AB  - The zebrafish, Danio rerio, has recently become the model system for the genetic
      analysis of vertebrate development. This paper reviews the advances in zebrafish
      cytogenetics, obtained through classical and molecular techniques, which will
      lead to the assignment of specific linkage groups to specific chromosome pairs in
      the zebrafish genome project. Several chromosome pairs of the 50-chromosome
      karyotype of D. rerio were differentially stained by classical staining
      techniques and additional information has been obtained by molecular
      cytogenetics. Indeed, the analysis of constitutive heterochromatin by C-banding
      and base-specific fluorochrome staining had suggested a differential composition
      of peri- and paracentromeric constitutive heterochromatin. The chromosome mapping
      of distinct AT- and GC-rich zebrafish satellite DNAs by means of PRINS (Primed in
      situ) and multicolor FISH (Fluorescence in situ Hybridization) has confirmed this
      hypothesis, which therefore provided the chromosome localization of 10% of the
      zebrafish genome. The analysis of nucleolus organizer regions (NORs) by silver
      staining and by FISH with 18S rDNA has also revealed the existence of variable
      and inactive NORs, in addition to those on the terminal regions of the long arms
      of the three NOR-bearing chromosome pairs. Other multicopy genes, such as minor
      ribosomal genes, or multicopy repeats, such as telomere specific sequences, have
      now been mapped on zebrafish chromosomes. The latest advancement in zebrafish
      molecular cytogenetics is the chromosome mapping of single locus genes. Single
      copy genes from each of the 25 genetic linkage groups are now being mapped on
      zebrafish chromosomes by using PAC clones.

PMID- 11841184
TI  - Extensive polymorphism and chromosomal characteristics of ribosomal DNA in a
      loach fish, Cobitis vardarensis (Ostariophysi, Cobitidae) detected by different
      banding techniques and fluorescence in situ hybridization (FISH).
AB  - When surveying the karyotype diversity of European loaches of the genus Cobitis
      to identify species involved in hybrid polyploid complexes, an extensive
      polymorphism in number and location of NORs was discovered in C. vardarensis
      using Ag-staining, C-banding, CMA3-fluorescence and fluorescence in situ
      hybridization (FISH). This species had 2n = 50, the karyotype contained 13 pairs
      of metacentric, 10 pairs of submetacentric and two pairs of subtelocentric
      chromosomes. The NOR-bearing chromosomes included one medium-sized metacentric
      pair with a large CMA3-positive heterochromatic pericentromeric block, one small
      metacentric as well as one large submetacentric pairs. Ribosomal sites were
      always located in telomeres of these chromosomes. Each of the pair of NOR-bearing
      chromosomes occurred in three variants - (1) presence and/or (2) absence of NORs
      on both homologues and (3) heterozygous combination where only one of the
      homologues bears NORs. Altogether, 10 different NOR cytotypes from 27
      theoretically possible ones were discovered among 20 indviduals examined. The
      number of NORs ranged from two to five per specimen. The results regarding the
      number and locations of NORs as revealed by banding techniques were confirmed
      using FISH with rDNA probe. NOR sites were of CMA3-positive, suggesting that
      ribosomal sites are associated with GC-rich DNA. Very similar structural
      polymorphism with multiple NORs is expressed in the Danubian loach C.
      elongatoides indicating a close relationship between both species.

PMID- 11841185
TI  - Flexibility on the karyotype evolution in bitterlings (Pisces, Cyprinidae).
AB  - In bitterlings (Acheilognathinae) C- and Ag-banding karyotypes of 6 species
      subspecies collected in China and South Korea were analyzed. The chromosomal
      constitution of 2n =46 (4 SM + 42 ST) in Rhodeus atremius fangi was quite
      different from that of 2n = 48 (8 M + 20 SM + 20 ST) in other species-subspecies
      in Rhodeus. It was concluded from the analysis of banded chromosomes that the
      increase in number of ST during the karyotype change from 2n = 48 to 2n = 46 was
      achieved by a series of pericentric inversions from 24 M-SM to 24 ST, and the
      decrease in the diploid number was caused by an additional tandem fusion of 4 ST
      chromosomes, forming a new ST pair in the 2n = 46 karyotype. The karyotype of
      Tanakia koreensis, T. signifer, and Acheilognathus macropterus is 2n = 48 (8 M +
      20 SM + 20 ST), 2n = 48 (8 M + 20 SM + 14-16 ST + 4-6 A), 2n = 44 (14M + 16 SM +
      14 ST), respectively. In R. ocellatus ocellatus, T. koreensis, T. signifer and A.
      macropterus, karyotype changes from 2n = 48 to 2n = 44 due to centric fusion and
      inversion have also been estimated. It was suggested that C-banding
      heterochromatin was greatly concerned with the karyotype evolution in
      bitterlings.

PMID- 11841186
TI  - Genetic mapping of Y-chromosomal DNA markers in Pacific salmon.
AB  - Sex chromosomes in fish provide an intriguing view of how sex-determination
      mechanisms evolve in vertebrates. Many fish species with single-factor sex
      determination systems do not have cytogenetically-distinguishable sex
      chromosomes, suggesting that few sex-specific sequences or chromosomal
      rearrangements are present and that sex-chromosome evolution is thus at an early
      stage. We describe experiments examining the linkage arrangement of a Y
      chromosomal GH pseudogene (GH-Y) sequence in four species of salmon (chum,
      Oncorhynchus keta; pink, O. gorbuscha; coho, O. kisutch; chinook, O.
      tshawytscha). Phylogenetic analysis indicates that GH-Y arose early in
      Oncorhynchus evolution, after this genus had diverged from Salmo and Salvelinus.
      However, GH-Y has not been detected in some Oncorhynchus species (O. nerka, O.
      mykiss and O. clarki), consistent with this locus being deleted in some lineages.
      GH-Y is tightly linked genetically to the sex-determination locus on the Y
      chromosome and, in chinook salmon, to another Y-linked DNA marker OtY1. GH-Y is
      derived from an ancestral GH2 gene, but this latter functional GH locus is
      autosomal or pseudoautosomal. YY chinook salmon are viable and fertile,
      indicating the Y chromosome is not deficient of vital genetic functions present
      on the X chromosome, consistent with sex chromosomes that are in an early stage
      of divergence.

PMID- 11841187
TI  - Cytogenetic and molecular analysis of the pufferfish Tetraodon fluviatilis
      (Osteichthyes).
AB  - In view of their compact genome, pufferfish (Tetraodontiformes) have been
      proposed as model animal for the study of the vertebrate genome. Despite such
      interest, cytogenetic information about puffers is still scanty. To fill this
      gap, a cytogenetic analysis of T. fluviatilis has been performed using both
      classical and molecular techniques. C-banding, followed by DAPI staining,
      evidenced that in T. fluviatilis, like all other puffer species so far examined,
      heterochromatin is essentially AT-rich and it is located at centromeres, whereas
      staining with CMA3, silver staining and FISH with a 28S ribosomal RNA gene DNA
      probe showed 2-4 nucleolar organizing regions (NORs) located in heterochromatic
      regions in the considered puffer species. FISH with the 5S probe put in evidence
      both in T. fluviatilis and in T. nigroviridis only a 5S cluster per haploid
      genome that is physically unlinked with the major ribosomal RNA genes including
      the 28S rRNA genes. Hybridization with the (TTAGGG)n probe showed in all the
      puffers brightly fluorescent signals uniform both in size and intensity at the
      end of all the chromosomes. Finally, mariner-like elements (MLEs) have been
      identified in T. fluviatilis and they have located into the NOR-associated
      heterochromatin.

PMID- 11841188
TI  - Two 5S rDNA arrays in neotropical fish species: is it a general rule for fishes?
AB  - In this paper we describe Southern blot hybridization results probed with 5S rRNA
      genes for several Neotropical fish species representing different taxonomic
      groups. All the studied species showed a general trend with the 5S rDNA tandem
      repeats organized in two distinct size-classes. At the same time, data on 5S rDNA
      organization in fish genome were summarized. Previous information on the
      organization and evolution of 5S rRNA gene arrays in the genome of this
      vertebrate group are in agreement with the Southern results here presented.
      Sequences obtained for several fish species have revealed the occurrence of two
      distinct 5S rDNA classes characterized by distinct nontranscribed spacer
      sequences, which are clustered in different chromosomes in some species.
      Moreover, the 5S rDNA loci are generally distributed in an interstitial position
      in the chromosomes and they are usually not syntenic to the 45S rDNA. The
      presence of two classes of 5S rDNA in several non-related fish species suggests
      that this could be a common condition for the 5S rRNA gene organization in the
      fish genome.

PMID- 11841190
TI  - Gene-centromere mapping of medaka sex chromosomes using triploid hybrids between
      Oryzias latipes and O. luzonensis.
AB  - Four sex-linked genetic markers (SL1, SL2, B2.38 and stsOPQ05-1) on the sex
      chromosomes of the medaka, O. latipes, were mapped in relation to the centromere
      by means of triploid hybrids between O. latipes and O. luzonensis. Female F1
      hybrid O. latipes of two inbred strains, Hd-rR and HNI, were crossed with male O.
      luzonensis. Triploidization was induced by heat-shock treatment. Hatching rate of
      heat-shock treated eggs was 59%, and that of untreated hybrid eggs was 2%,
      indicating that most of the hatched fry were triploid. Using these triploid
      hatched fry, the map distances between the four loci and the centromere were
      examined. The order was SL2 - centromere - SL1 - B2.38 - stsOPQ05-1 and the map
      distances were: SL2 - centromere, 1%; centromere - SL1, 18%; SL1 - B2.38, 19%;
      B2.38 - stsOPQ05-1, 9%. Previous studies using FISH showed that SL2 is located on
      the short arm of large submetacentric chromosomes, and SL1 was closely linked to
      SDF (sex-determining factor). The results of gene-centromere mapping of this
      study show that SL1, B2.38 and stsOPQ05-1 are located on the long arm, and that.
      SDF is thus also on the long arm of the sex chromosomes.

PMID- 11841189
TI  - Microsatellite-centromere mapping in the loach, Misgurnus anguillicaudatus.
AB  - Primer sets for 15 polymorphic microsatellite loci were developed in the loach,
      Misgurnus anguillicaudatus (Cobitidae) by molecular cloning and sequencing
      techniques. Mendelian inheritance was confirmed for the 15 loci by examining the
      genotypic segregation produced with the primer sets in two full-sib families. The
      loci were mapped in relation to their centromere in four gynogenetic diploid
      lines, which were induced by inhibition of the second meiotic division after
      fertilization with genetically inert sperm. Microsatellite-centromere
      recombination rates ranged between 0.06 and 0.95 under the assumption of complete
      interference. Thus, these loci are distributed from the centromeres to the
      telomeres of their respective chromosomes. The success of mitotic gynogenesis,
      produced by suppression of the first cleavage, was verified by homozygosity at
      three diagnostic microsatellite loci that exhibited high gene-centromere meiotic
      recombination rates in the same family. The differences in heterozygosity levels
      observed with these markers were attributed to differences in the temporal
      application of heat shock following inert sperm activation.

PMID- 11841191
TI  - Improved fish lymphocyte culture for chromosome preparation.
AB  - Cytogenetic methodology is still underdeveloped in fishes compared with mammals.
      Culture condition for fish lymphocytes was optimized to improve chromosome
      preparation using the rainbow trout (Oncorhynchus mykiss) as a model after
      changing the combination of parameters such as mitogens, incubation periods,
      media, cell components, and freshness of blood. The optimized culture condition
      included isolation of lymphocytes from fresh blood by a stirring method, their
      culture in medium 199 supplemented with 10% FBS, 18 microg/ml of
      phytohemagglutinin (PHA-W) and 100 microg/ml of lipopolysaccharide (LPS) as
      mitogens, and harvested at 6 days after culture. This condition provided a
      notably increased mitotic index (MI) of 4.3-10.0% in rainbow trout lymphocytes.
      In addition, the condition was highly reproducible as shown by the similar level
      of MI in cultured lymphocytes from 181 individuals without failure. Applicability
      of this method in a wide range of fish groups was also proven with Ml of 1.1
      13.3% in cultured lymphocytes from other 16 freshwater species of Acipenseridae,
      Anguillidae, Solmonidae, Cyprinidae, and Centrarchidae, and five marine species
      of Sparidae, Kyphosidae, Paralichthyidae, and Scorpaenidae. Chromosome
      preparations of improved quality by the present method were successfully applied
      for the replication R-banding with incorporation of 5-bromo-2'-deoxyuridine and
      direct R-banding fluorescence in situ hybridization.

PMID- 11841192
TI  - Morphologically differentiated sex chromosomes in neotropical freshwater fish.
AB  - A general survey of the occurrence of morphologically differentiated sex
      chromosomes in the neotropical freshwater fishes is presented. The total number
      of 32 occurrences involving simple XX-XY and ZZ-ZW, and multiple X1X2Y, XY1Y2 and
      ZW1W2 sex chromosome systems is described, with comments on the aspects of sex
      chromosome evolution in this fish fauna. The occurrence of different sex
      chromosome systems in related species of the same genus, or in different
      populations of the same nominal species, involving male and sometimes female
      heterogamety, and differences in the molecular composition of sex-linked
      heterochromatin, are considered as indicative of the early stage of sex
      chromosomes evolution in fish.

PMID- 11841193
TI  - Potential antioxidant mechanism of action for metronidazole: implications for
      rosacea management.
AB  - Chronic inflammation is believed to account for some symptoms of rosacea. The
      efficacy of topical metronidazole in the treatment of rosacea may be due to its
      antimicrobial as well as anti-inflammatory activity. Neutrophils release potent
      inflammatory mediators, including reactive oxygen species (ROS), and
      intrafollicular neutrophils have been observed in stage II disease. ROS and other
      free radicals may contribute to intrinsic and extrinsic aging, both of which
      accentuate clinical manifestations of rosacea. If, as in vitro data suggest,
      metronidazole has antioxidant activity, it may help subdue the oxidative tissue
      damage of intrinsic and extrinsic aging as well as prevent and treat rosacea
      symptoms.

PMID- 11841194
TI  - Clindamycin phosphate 1% gel in acne vulgaris.
AB  - A 12-week study compared Clindagel, a unique water-based gel formulation of
      clindamycin phosphate 1%, administered once daily, and Cleocin T, a slightly
      different gel formulation indicated for twice-daily use, in the treatment of acne
      vulgaris. Clindagel was safe and effective and equivalent to Cleocin T gel,
      albeit with a better tolerability profile. Clindagel is a viable alternative to
      Cleocin T gel.

PMID- 11841195
TI  - Corticosteroids administered by nebulization to children with bronchial asthma.
AB  - Inhaled corticosteroids are recommended for long-term control of asthma in
      children, and nebulization simplifies administration to patients who lack hand-to
      lung coordination. Information on the efficacy and safety of nebulized
      corticosteroids in children with mild to moderate asthma is limited, however, and
      comparison between corticosteroids is lacking. One hundred thirty-three patients
      6 to 14 years of age with bronchial asthma were randomly assigned to receive
      flunisolide 500 microg or budesonide 500 microg, both administered twice daily by
      nebulizer for 4 weeks. Morning peak expiratory flow rate (primary efficacy
      endpoint) increased significantly from baseline (P<.001) with both medications (P
      = NS between treatments). Use of salbutamol as rescue medication decreased by
      82.6% with flunisolide and by 82.7% with budesonide; respective decreases in
      asthma score were 78.8% and 82.3% (P<.001 vs baseline, P = NS between
      treatments). Only flunisolide reduced the number of nocturnal awakenings
      (P<.001). Ten patients in the flunisolide group and 12 in the budesonide group
      reported adverse events, none of which required discontinuation of treatment. In
      children with asthma, nebulized corticosteroids are effective and have good
      safety and tolerability profiles. Flunisolide and budesonide seem to produce
      equivalent clinical responses.

PMID- 11841196
TI  - Oral beclomethasone dipropionate in patients with mild to moderate ulcerative
      colitis: a dose-finding study.
AB  - Systemic glucocorticosteroids have demonstrated efficacy in ulcerative colitis
      (UC) but cause undesired systemic side effects. Beclomethasone dipropionate (BDP)
      has potent topical activity and is extensively metabolized. This randomized
      double-blind study investigated an oral gastroresistant controlled-release
      preparation of BDP in 57 patients with mild to moderately severe extensive or
      left-sided UC. Patients were assigned to receive BDP 5 or 10 mg/d; a third group
      took a clinically inactive dose (1.6 g/d) of 5-aminosalicylic acid (5-ASA). Both
      BDP doses displayed excellent efficacy confirmed by results of endoscopy, biopsy,
      and clinical evaluation. Significant improvement from baseline occurred in most
      signs and symptoms of UC, particularly stool frequency, rectal bleeding, and
      mucus in the stool (P<.01). Tolerability was good in both BDP groups. Morning
      plasma cortisol levels decreased significantly from baseline with BDP 10 mg, but
      no significant changes in vital signs were observed at the end of treatment.
      Despite a small sample size and the open comparison with 5-ASA, this multicenter
      study showed the therapeutic equivalence of BDP 5 and 10 mg/d in alleviating
      clinical symptoms and improving endoscopic and biopsy scores in patients with
      mild to moderate UC. BDP 5 mg/d displayed better general tolerability and less
      reduction of plasma cortisol levels, however, and may be preferable to the higher
      dose in this indication.

PMID- 11841197
TI  - Medication adherence: a key factor in effective management of rosacea.
AB  - Rosacea is a chronic condition associated with relapses. Unsuccessful treatment
      is predicated, in part, on suboptimal adherence with the medication regimen.
      Motivating long-term compliance remains a challenge. The literature on adherence
      with rosacea medication is scant, but data from other diseases suggest that a
      multifactorial approach combining nonpharmacologic and adherence-enhancing
      pharmacologic interventions appears to offer the greatest success. The variety of
      topical metronidazole formulations that are relatively well tolerated and
      convenient to administer has been a notable advance in rosacea management. The
      dermatologist, by emphasizing the importance of adherence with therapy, can do
      much to facilitate this most critical behavior.

PMID- 11841198
TI  - Switching patients with glaucoma or ocular hypertension from dual therapy to
      monotherapy: evaluation of brimonidine as a model.
AB  - A multicenter open-label study investigated the clinical effectiveness and
      economic feasibility of switching 142 patients from dual therapy to twice-daily
      monotherapy with brimonidine for glaucoma or ocular hypertension. Evaluations
      were performed at baseline and 2 (visit 2) and 8 (visit 3) weeks after the
      switch. Patients completed a questionnaire that rated medication-related visual
      function and satisfaction (comfort, convenience, vision, ease of remembering to
      use drops) at each visit. At visit 3, investigators, taking into account IOP
      measurements, safety, and responses on the questionnaire, recommended whether the
      patient should remain on brimonidine. A pharmacoeconomic analysis, including the
      number of visits, cost of medication, and success rates, compared the cost of
      dual therapy with that of switching to brimonidine monotherapy. Of the 131
      patients who completed the study, 77 (59%) had no change or a decrease in IOP
      from baseline, and 53 (41%) had an increase. Investigators recommended that 77%
      of the study completers continue to take brimonidine monotherapy. Extending
      treatment with brimonidine for 12 months would achieve a significant cost savings
      of 16%. Brimonidine monotherapy is an efficacious and cost-effective alternative
      to dual therapy for glaucoma and ocular hypertension. Appropriate monotherapy may
      be as effective as dual therapy for many patients, and a clinically relevant
      trial such as this may be economically advantageous for testing a switch.

PMID- 11841199
TI  - The Ni-containing carbon monoxide dehydrogenase family: light at the end of the
      tunnel?

PMID- 11841200
TI  - Duplicated dockerin subdomains of Clostridium thermocellum endoglucanase CelD
      bind to a cohesin domain of the scaffolding protein CipA with distinct
      thermodynamic parameters and a negative cooperativity.
AB  - Mutagenized dockerin domains of endoglucanase CelD (type I) and of the
      cellulosome-integrating protein CipA (type II) were constructed by swapping
      residues 10 and 11 of the first or the second duplicated segment between the two
      polypeptides. These residues have been proposed to determine the specificity of
      cohesin-dockerin interactions. The dockerin domain of CelD still bound to the
      seventh cohesin domain of CipA (CohCip7), provided that mutagenesis occurred in
      one segment only. Binding was no longer detected by nondenaturing gel
      electrophoresis when both segments were mutagenized. The dockerin domain of CipA
      bound to the cohesin domain of SdbA as long as the second segment was intact.
      None of the mutated dockerins displayed detectable binding to the noncognate
      cohesin domain. Isothermal titration calorimetry showed that binding of the CelD
      dockerin to CohCip7 occurred with a high affinity [K(a) = (2.6 +/- 0.5) x 10(9)
      M(-1)] and a 1:1 stoichiometry. The reaction was weakly exothermic (DeltaHdegrees
      = -2.22 +/- 0.2 kcal x mol(-1)) and largely entropy driven (TDeltaSdegrees =
      10.70 +/- 0.5 kcal x mol(-1)). The heat capacity change on complexation was
      negative (DeltaC(p) = -305 +/- 15 cal x mol(-1) x K(-1)). These values show that
      cohesin-dockerin binding is mainly hydrophobic. Mutations in the first or the
      second dockerin segment reduced or enhanced, respectively, the hydrophobic
      character of the interaction. Due to partial enthalpy-entropy compensation, these
      mutations induced only small changes in binding affinity. However, the binding
      affinity was strongly decreased when both segments were mutated, indicating
      strong negative cooperativity between the two mutated sites.

PMID- 11841201
TI  - Mapping by site-directed mutagenesis of the region responsible for cohesin
      dockerin interaction on the surface of the seventh cohesin domain of Clostridium
      thermocellum CipA.
AB  - To locate the region involved in binding dockerin domains, 15 mutations were
      introduced across the surface of the seventh cohesin domain of the scaffolding
      protein CipA, which holds together the cellulosome of Clostridium thermocellum.
      Mutated residues were located on both faces of the nine-stranded beta-sandwich
      forming the cohesin domain and on the loops connecting beta-strands 4 and 5, 6
      and 7, and 8 and 9. The loop region was previously proposed, on the basis of
      sequence comparisons, to form a contiguous "recognition strip". Individual
      mutants of four residues, D39, Y74, E86, and G89, formed no complexes detectable
      by nondenaturing gel electrophoresis after incubation with CelD664, a shortened
      form of endoglucanase CelD lacking the residues linking the catalytic domain with
      the dockerin domain. The four sensitive residues encompass a hydrophobic region
      on the 5-6-3-8 face of the molecule, which overlaps partially with the
      recognition strip and with a hydrophobic zone involved in the formation of
      cohesin-cohesin dimers. Isothermal titration calorimetry showed that single
      cohesin mutations affecting the binding of CelD664 had significant effects on the
      enthalpy or entropy of binding of wild-type CelD but much lesser effects on the
      association constant, owing to enthalpy-entropy compensation. However, the
      affinity for wild-type CelD of the triple mutant affecting D39, Y74, and E86 was
      reduced by 2 orders of magnitude, due to negative cooperativity between mutations
      affecting D39 + Y74 on one hand and E86 on the other hand.

PMID- 11841202
TI  - Contribution of hydrogen bonding to protein stability estimated from isotope
      effects.
AB  - An unresolved issue in structural biology concerns the relative contribution of H
      bonds to protein stability. We use the small molecules 4-acetamidobenzoic acid
      and N-acetylanthranilic acid as model compounds to relate the energetic
      contribution from hydrogen bonds (H bonds) to the deuterium/hydrogen amide
      isotope effect. N-Acetylanthranilic acid models carbonyl-amide H bonds formed
      during protein folding; 4-acetamidobenzoic acid models the unfolded state in
      which the amide H bonds to water. NMR is used to measure shifts in the pK(a) of
      the ionizable carboxyl group when the amides of the compounds are either
      protonated or deuterated. From the pK(a) shift, we obtain a quantitative scale
      factor: SF = partial partial differential(DeltaG(HB))/partial partial
      differential(RT ln Phi), where DeltaG(HB) is the change in free energy of an H
      bond upon isotope substitution and Phi is the fractionation factor. Isotope
      effect data also are reported for a small globular protein, lambda repressor,
      using the "C(m) experiment". The protein's isotope effect, which reports on the
      shape of the energy well, is converted to H-bonding free energy by applying the
      scale factor. We estimate that amide-related H bonds (amide-carbonyl and amide
      water) contribute favorably to protein stability by approximately 30-50 kcal/mol
      in lambda repressor, GCN4 coiled coil, and cytochrome c but unfavorably by
      approximately 6 kcal/mol in ubiquitin. The results indicate that H-bond strength
      varies from one protein to another and presumably at different sites within the
      same protein.

PMID- 11841203
TI  - NMR structural study of two-disulfide variant of hen lysozyme: 2SS[6-127, 30-115]
      -a disulfide intermediate with a partly unfolded structure.
AB  - The 15N-labeled recombinant hen lysozyme and two species of two-disulfide
      variants, denoted as 2SS[6-127, 30-115] and 2SS[64-80, 76-94], were studied by
      means of NMR spectroscopy. The former variant contains two disulfide bridges in
      the alpha-domain, while the latter has one disulfide bridge in the beta-domain
      and the other one at the interface between two domains. Resonance assignments
      were performed using 3D TOCSY-HSQC and NOESY-HSQC spectra. The 15N-1H-HSQC
      spectrum of 2SS[6-127, 30-115] was similar to that of recombinant lysozyme as a
      whole, although a number of cross-peaks disappeared. On the other hand, the HSQC
      spectrum of 2SS[64-80, 76-94] was characteristic of unfolded proteins. The
      structure of 2SS[6-127, 30-115] was thoroughly examined on the basis of NOE
      contacts determined by NMR spectroscopy. The structure of the alpha-domain was
      quite similar to that of authentic lysozyme, while the beta-domain was largely
      unstructured. However, NMR data clearly demonstrated that some residual
      structures exist in the beta-domain. The beta1 and beta2 strands were maintained
      stably as an antiparallel beta-sheet. In addition, the residues 55 and 56 were
      located in the vicinity of the end of the B-helix. Further, the C-helix was
      properly set with side-chains of I88, V92, K96, and V99 facing toward the
      hydrophobic core in the alpha-domain. These residual structures inherent in the
      amino acid sequence were evaluated concerning the folding process of lysozyme.
      Our experiments imply that the establishment of the backbone conformation ranging
      from residues 76-99 plays a key role in attaining the cooperativity between two
      domains required for the folding transition.

PMID- 11841204
TI  - Native state EX2 and EX1 hydrogen exchange of Escherichia coli CspA, a small beta
      sheet protein.
AB  - Escherichia coli CspA is a small all-beta-sheet protein that folds fast (tau = 4
      ms) via an apparent two-state mechanism. Our previous studies have shown that a
      large aromatic cluster on the surface of the protein participates in the rate
      limiting step of folding and thus may be part of the folding nucleus of this
      protein. To obtain a more detailed picture of molecular events at the peptide
      backbone during unfolding and folding of CspA, we used native state hydrogen
      exchange and nuclear magnetic resonance spectroscopy (NMR). The experiments with
      native CspA were performed over a range of pH values from low pH, where exchange
      is governed by a rapid equilibrium before chemical exchange (EX2 exchange), to
      high pH, where exchange is dictated by the rate of unfolding (EX1 exchange).
      Rates of folding and unfolding were determined for 11 residues. The distribution
      of rates of folding within the structure of CspA suggests that hairpin turns,
      including one near the aromatic cluster, may nucleate the folding of CspA.

PMID- 11841205
TI  - NMR studies of the antibody-bound conformation of a carbohydrate-mimetic peptide.
AB  - Transferred nuclear Overhauser enhancement (TRNOE) experiments have been
      performed at 800 MHz to investigate the bound conformation of the hexapeptide
      DRPVPY, a functional molecular mimic of the group A Streptococcus cell-wall
      polysaccharide. The hexapeptide binds to the monoclonal antibody SA-3, mimicking
      the branched trisaccharide repeating unit, L-Rha-alpha-(1 --> 2)-(D-GlcNAc-beta
      (1 --> 3))-alpha-L-Rha (Rha, rhamnose; GlcNAc, N-acetylglucosamine). The peptide
      adopts a tight turn conformation with close contacts between the side chains of
      valine and tyrosine. Relaxation network editing experiments (QUIET-NOESY) were
      used to confirm the validity of the observed contacts and to evaluate the
      presence of spin diffusion pathways. Saturation transfer difference (STD-NMR)
      experiments with selective saturation of protein resonances revealed enhancements
      of many of the peptide resonances due to close contacts between the peptide and
      the protein within the antibody combining site.

PMID- 11841206
TI  - Novel activity of Escherichia coli mismatch uracil-DNA glycosylase (Mug) excising
      8-(hydroxymethyl)-3,N4-ethenocytosine, a potential product resulting from
      glycidaldehyde reaction.
AB  - Glycidaldehyde is an industrial chemical which has been shown to be genotoxic in
      in vitro experiments and carcinogenic in rodent studies. It is a bifunctional
      alkylating agent capable of reacting with DNA to form exocyclic hydroxymethyl
      substituted ethenobases. In this work, 8-(hydroxymethyl)-3,N4-etheno-2'
      deoxycytidine (8-HM-epsilondC), a potential nucleoside derivative of
      glycidaldehyde, was synthesized using phosphoramidite chemistry and site
      specifically incorporated into a defined 25-mer oligodeoxynucleotide. The 8-HM
      epsilonC adduct is structurally related to 3,N4-ethenocytosine (epsilonC), a
      product of reaction with vinyl chloride or through lipid peroxidation. In
      Escherichia coli, epsilonC has been shown previously to be a primary substrate
      for the mismatch uracil-DNA glycosylase (Mug). In this study, we report that the
      same glycosylase also acts on 8-HM-epsilonC in an oligonucleotide duplex. The
      enzyme binds to the 8-HM-epsilonC-oligonucleotide to a similar extent as the
      epsilonC-oligonucleotide. The Mug excision activity toward 8-HM-epsilonC is
      approximately 2.5-fold lower than that toward the epsilonC substrate. Both
      activities can be stimulated up to approximately 2-fold higher by the addition of
      E. coli endonuclease IV. These two adducts, when mispaired with normal bases,
      were all excised from DNA by Mug with similar efficiencies. Structural studies
      using molecular simulations showed similar adjustment and hydrogen bonding
      pattern for both 8-HM-epsilonC*G and epsilonC*G pairs in oligomer duplexes. We
      believe that these findings may have biological and structural implications in
      defining the role of 8-HM-epsilonC in glycosylase recognition/repair.

PMID- 11841207
TI  - Recombination analysis of the human minisatellite MsH42 suggests the existence of
      two distinct pathways for initiation and resolution of recombination at MsH42 in
      rat testes nuclear extracts.
AB  - We have previously described a GC-rich human minisatellite, termed MsH42, which
      exists in two allelic forms, long and short. Here, we have identified a third
      allele of medium length and localized the MsH42 locus in the chromosome 15q25.1
      inside an intron belonging to a gene of unknown function. The recombinogenic
      potential of the three alleles was assayed in vitro incubating pBR322-based
      constructs containing two copies of the minisatellite MsH42 with its flanking
      sequences, in the presence of rat testes nuclear extracts. This assay system was
      configured to monitor only reciprocal exchange type events and not gene
      conversion. All MsH42 allelic sequences enhanced intramolecular homologous
      recombination promoting high rates (approximately 76%) of equal crossover, the
      long allele showing the highest recombinogenic activity. Removal of the MsH42
      long allele flanking sequences, which are identical in the three alleles,
      provoked a decrease in the enhancement of recombination and in the frequency of
      equal crossovers, suggesting that these sequences are important for the
      recombinogenic activity and for the correct pairing between homologous sequences.
      The occurrence of some complex recombination events within the minisatellite
      MsH42 suggests the existence of processes related to polymerase slippage and
      unwinding with reinvasion during the repair synthesis. Our findings point toward
      the existence of two distinct biochemical pathways for initiation and resolution
      of recombination at the minisatellite MsH42. Finally, the in vitro recombination
      system employed in this study could provide an approach to dissect processes of
      repetitive DNA instability and recombination.

PMID- 11841209
TI  - Insertion of a reversible redox switch into a rare-cutting DNA endonuclease.
AB  - Target sites for homing endonucleases occur infrequently in complex genomes. As a
      consequence, these enzymes can be used in mammalian systems to introduce double
      strand breaks at recognition sites inserted within defined loci to study DNA
      repair by homologous and nonhomologous recombination. Using homing endonucleases
      for gene targeting in vivo would be more feasible if temporal or spatial
      regulation of their enzymatic activity were possible. Here, we show that the DNA
      cleavage activity of the yeast PI-SceI homing endonuclease can be turned on and
      off using a redox switch. Two cysteine pairs (Cys-64/Cys-344 and Cys-67/Cys-365)
      were separately inserted into flexible DNA binding loop(s) to create disulfide
      bonds that lock the endonuclease into a nonproductive conformation. The cleavage
      activities of the reduced Cys-64/Cys-344 and Cys-67/Cys-365 variants are similar
      or slightly lower than that of the control protein, but the activities of the
      proteins in the oxidized state are decreased more than 30-fold. Modulating the
      activity of the proteins is easily accomplished by adding or removing the
      reducing agent. We show that defects in DNA binding account for the decreased DNA
      cleavage activities of the proteins containing disulfide bonds. Interestingly,
      the Cys-67/Cys-365 variant toggles between two different DNA binding
      conformations under reducing and oxidizing conditions, which may permit the
      identification of structural differences between the two states. These studies
      demonstrate that homing endonuclease activity can be controlled using a molecular
      switch.

PMID- 11841208
TI  - Structure-based design of a leucine zipper protein with new DNA contacting
      region.
AB  - We have employed a structure-based design to construct a small folding domain
      from the F-actin bundling protein villin that contains the amino acids necessary
      for the DNA binding of the basic leucine zipper protein GCN4 and have compared
      its DNA binding with GCN4. The monomeric motif folds into a stable domain and
      binds DNA in a rigid-body mechanism, while its affinity is not higher than that
      of the basic region peptide. The addition of the leucine zipper region to the
      folded domain restored its sequence-specific DNA binding comparable to that of
      GCN4. Unlike the monomeric folded domain, its leucine zipper derivative undergoes
      a conformational change upon DNA binding. CD spectral and thermodynamic studies
      indicate that the DNA-contacting region is folded in the presence or absence of
      DNA and suggest that the junction between the DNA-contacting and the leucine
      zipper regions transits to a helix in the presence of DNA. These results
      demonstrate that the structural transition outside the direct-contacting region,
      which adjusts the precise location of the DNA-contacting region, plays a critical
      role in the specific complex formation of basic leucine zipper proteins.

PMID- 11841211
TI  - Structure of Escherichia coli aminodeoxychorismate synthase: architectural
      conservation and diversity in chorismate-utilizing enzymes.
AB  - Aminodeoxychorismate synthase is part of a heterodimeric complex that catalyzes
      the two-step biosynthesis of 4-amino-4-deoxychorismate, a precursor of p
      aminobenzoate and folate in microorganisms. In the first step, a glutamine
      amidotransferase encoded by the pabA gene generates ammonia as a substrate that,
      along with chorismate, is used in the second step, catalyzed by
      aminodeoxychorismate synthase, the product of the pabB gene. Here we report the X
      ray crystal structure of Escherichia coli PabB determined in two different
      crystal forms, each at 2.0 A resolution. The 453-residue monomeric PabB has a
      complex alpha/beta fold which is similar to that seen in the structures of
      homologous, oligomeric TrpE subunits of several anthranilate synthases of
      microbial origin. A comparison of the structures of these two classes of
      chorismate-utilizing enzymes provides a rationale for the differences in
      quaternary structures seen for these enzymes, and indicates that the weak or
      transient association of PabB with PabA during catalysis stems at least partly
      from a limited interface for protein interactions. Additional analyses of the
      structures enabled the tentative identification of the active site of PabB, which
      contains a number of residues implicated from previous biochemical and genetic
      studies to be essential for activity. Differences in the structures determined
      from phosphate- and formate-grown crystals, and the location of an adventitious
      formate ion, suggest that conformational changes in loop regions adjacent to the
      active site may be needed for catalysis. A surprising finding in the structure of
      PabB was the presence of a tryptophan molecule deeply embedded in a binding
      pocket that is analogous to the regulatory site in the TrpE subunits of the
      anthranilate synthases. The strongly bound ligand, which cannot be dissociated
      without denaturation of PabB, may play a structural role in the enzyme since
      there is no effect of tryptophan on the enzymic synthesis of
      aminodeoxychorismate. Extensive sequence similarity in the tryptophan-binding
      pocket among several other chorismate-utilizing enzymes, including isochorismate
      synthase, suggests that they too may bind tryptophan for structural integrity,
      and corroborates early ideas on the evolution of this interesting enzyme family.

PMID- 11841210
TI  - Characterization of the carboxylate delivery module of transcarboxylase:
      following spontaneous decarboxylation of the 1.3S-CO2- subunit by NMR and FTIR
      spectroscopies.
AB  - Transcarboxylase (TC) is a multisubunit enzyme that catalyzes the transfer of a
      carboxylate group from methylmalonyl-CoA (MMCoA) to pyruvate. The CO2- group is
      shuttled between the MMCoA and pyruvate binding sites by a biotin cofactor,
      covalently linked to the 1.3S subunit. Fully carboxylated 1.3S can be prepared in
      vitro using 1.3S, MMCoA, and catalytic amounts of the TC's MMCoA-binding subunit.
      The 1.3S-CO2- intermediate decarboxylates spontaneously over a period of hours,
      and this process was characterized by 1D and 2D NMR and FTIR spectroscopies. The
      NMR data yielded a first-order kinetic constant of 1.4 x 10(-3) min(-1) for the
      spontaneous decarboxylation. This rate was calculated from the 1D NMR spectrum by
      measuring the reappearance of biotin's ureido NH protons and the disappearance of
      peaks at 6.99 and 7.67 ppm assigned to Asn-8 and/or Asn-24 from the 1.3S's N
      terminus. The latter peaks are absent in the 1D spectrum of non-carboxylated 1.3S
      due to exchange between two or more conformations within the N-terminus causing
      line broadening. It is proposed that interactions between the biotin-CO2- and the
      N-terminal amino acids perturb this conformational equilibrium causing some N
      terminal residues to appear in the 1D NMR spectrum of the carboxylated form.
      Further details are apparent from a comparison of the 2D spectra of the 1.3S-CO2-
      and 1.3S proteins, where carboxylation causes several peaks from the C-terminal
      half to shift as well as the appearance of resonances due to some residues
      located at the N-terminal half of the protein. FTIR difference spectra were used
      also to follow spontaneous decarboxylation of the 1.3S-CO2-. For the carboxylated
      1.3S, the difference spectra provided the vibrational signature of the CO2- on
      the biotin ring. A doublet was identified at 1695 and 1699 cm(-1) that increased
      in intensity with increasing t. This is assigned to an antisymmetric stretching
      vibration of the CO2- group bound to biotin on the 1.3S protein. Its position and
      profile provide further evidence for interactions occurring between the biotin
      CO2- group and the 1.3S protein. These studies demonstrate the highly mobile,
      "poised" nature of the 1.3S protein engineered for its role as a CO2-
      translocator.

PMID- 11841212
TI  - Crystal structure of Vat(D): an acetyltransferase that inactivates streptogramin
      group A antibiotics.
AB  - The streptogramin class of antibiotics act to inhibit bacterial protein
      synthesis, and their semisynthetic derivatives, such as dalfopristin-quinupristin
      (Synercid), are used to treat serious or life-threatening infections due to
      multiply antibiotic resistant bacteria. Acquired resistance of the nosocomial
      pathogen Enterococcus faecium to the group A component of natural and
      semisynthetic streptogramin mixtures is a prerequisite for the streptogramin
      resistance phenotype and is mediated by a streptogramin acetyltransferase. The
      crystal structure of Vat(D), a streptogramin acetyltransferase from a human
      urinary isolate of E. faecium, has been determined as an apoenzyme and in complex
      with either acetyl-CoA or virginiamycin M1 and CoA. These structures illustrate
      the location and arrangement of residues at the active site, and point to His 82
      as a residue that may function as a general base. The structural similarity of
      Vat(D) to the xenobiotic acetyltransferase from Pseudomonas aeruginosa indicates
      similarities in the catalytic mechanism for these enzymes as well as several
      shared and distinctive antibiotic binding interactions between these enzymes and
      their respective substrates. These results reveal the molecular basis for a
      reaction by which Gram-positive cocci acquire resistance to a last resort
      antibiotic.

PMID- 11841213
TI  - Three subunits contribute amino acids to the active site of tetrameric
      adenylosuccinate lyase: Lys268 and Glu275 are required.
AB  - Tetrameric adenylosuccinate lyase (ASL) of Bacillus subtilis catalyzes the
      cleavage of adenylosuccinate to form AMP and fumarate. We previously reported
      that two distinct subunits contribute residues to each active site, including the
      His68 and His89 from one and His141 from a second subunit [Brosius, J. L., and
      Colman, R. F. (2000) Biochemistry 39, 13336-13343]. Glu(275) is 2.8 A from His141
      in the ASL crystal structure, and Lys268 is also in the active site region;
      Glu275 and Lys268 come from a third, distinct subunit. Using site-directed
      mutagenesis, we have replaced Lys268 by Arg, Gln, Glu, and Ala, with specific
      activities of the purified mutant enzymes being 0.055, 0.00069, 0.00028, and 0.0,
      respectively, compared to 1.56 units/mg for wild-type (WT) enzyme. Glu275 was
      substituted by Gln, Asp, Ala, and Arg; none of these homogeneous mutant enzymes
      has detectable activity. Circular dichroism and light scattering reveal that
      neither the secondary structure nor the oligomeric state of the Lys268 mutant
      enzymes has been perturbed. Native gel electrophoresis and circular dichroism
      indicate that the Glu275 mutant enzymes are tetramers, but their conformation is
      altered slightly. For K268R, the K(m)s for all substrates are similar to WT
      enzyme. Binding studies using [2-3H]-adenylosuccinate reveal that none of the
      Glu275 mutant enzymes, nor inactive K268A, can bind substrate. We propose that
      Lys268 participates in binding substrate and that Glu275 is essential for
      catalysis because of its interaction with His141. Incubation of H89Q with K268Q
      or E275Q leads to restoration of up to 16% WT activity, while incubation of H141Q
      with K268Q or E275Q results in 6% WT activity. These complementation studies
      provide the first functional evidence that a third subunit contributes residues
      to each intersubunit active site of ASL. Thus, adenylosuccinate lyase has four
      active sites per enzyme tetramer, each of which is formed from regions of three
      subunits.

PMID- 11841214
TI  - Obelin from the bioluminescent marine hydroid Obelia geniculata: cloning,
      expression, and comparison of some properties with those of other Ca2+-regulated
      photoproteins.
AB  - A cDNA encoding the Ca2+-regulated photoprotein of the bioluminescent marine
      hydroid Obelia geniculata was cloned and sequenced. The cDNA is a 774 bp fragment
      containing two overlapping open reading frames, one of which contained 585 bp
      encoding a 195 amino acid polypeptide which obviously has the primary structure
      of the apoprotein of a calcium-regulated photoprotein. Many of the residues are
      identical to those in other Ca2+-regulated photoproteins: 86% compared with that
      from Obelia longissima, 76% with that from Clytia (Phialidium), 64% with that
      from Aequorea, and 64% with that from Mitrocoma(Halistaura). The obelin from O.
      geniculata was overexpressed in Escherichia coli, refolded from inclusion bodies,
      and purified. The yield of highly purified recombinant protein was 55-80 mg/L of
      LB medium. O. geniculata obelin has absorption maxima at 280 and 460 nm and a
      shoulder at approximately 310 nm. The calcium-discharged protein loses visible
      absorption but exhibits a new absorption maximum at 343 nm. The bioluminescence
      of the obelin from O. geniculata is blue (lambda(max) = 495 nm). In contrast, the
      fluorescence of the calcium-discharged protein is yellow-green (lambda(max) = 520
      nm; excitation at 340 nm). This is in sharp contrast to aequorin in which the
      bioluminescence and fluorescence emission spectra of the calcium-discharged
      protein are almost identical (lambda(max) = 465 nm). The Ca2+ concentration
      effect curve for O. geniculata obelin is similar to those of many other
      photoproteins: at [Ca2+] below approximately 10(-8) M, calcium-independent
      luminescence is observed, and at [Ca2+] approximately 10(-3) M, the luminescence
      reaches a maximum. Between these extremes, the curve spans a vertical range of
      almost 8 log units with a maximum slope on a log-log plot of about 2.5. In the
      absence of Mg2+ the rate constant for the rise of bioluminescence determined by
      the stopped-flow technique is about 450 s(-1). The effects of Mg2+ on the
      kinetics of bioluminescence are complicated, but at all concentrations studied
      they are relatively small compared to the corresponding effects on aequorin
      luminescence. At least with respect to speed and sensitivity to Mg2+, the obelins
      from both O. longissima and O. geniculata would appear to be more suitable than
      aequorin for use as intracellular Ca2+ indicators.

PMID- 11841216
TI  - Native-like interactions favored in the unfolded bovine pancreatic trypsin
      inhibitor have different roles in folding.
AB  - Folding kinetics of a series of bovine pancreatic trypsin inhibitor (BPTI)
      variants with similar stabilities and structures have been measured. All are
      strongly destabilized relative to WT. In Y21A, F22A, Y23A, G37A, and F45A, the
      three native disulfide bonds are retained. In RM(14-38), Cys14 and Cys38 thiols
      are methylated while C30-C51 and C5-C55 disulfides remain intact. At pH 2 and 20
      degrees C, relaxation rate constants of the major kinetic phase range from
      approximately 10 ms to 0.71 s in the absence of denaturant. All mutants except
      G37A exhibit standard two-state behavior. Y21A, F22A, and Y23A fold much more
      slowly than other mutants. The experiments were designed to test the hypothesis
      that native-like structure detected in the unfolded BPTI is important in folding.
      Two native-like contacts are implied by NOEs in reduced and unfolded BPTI,
      between residues Tyr23 and Ala25, and between Gly37 NH and the Tyr35 ring. The
      results support an earlier hypothesis that formation of the central beta-hairpin,
      monitored by a local native interaction between Tyr23 and Ala25, is crucial to
      initiation of BPTI folding. The second native-like contact is important, not in
      folding initiation, but in preventing a kinetic trap later in the process.
      Evidence for this comes from mutant G37A, which behaves very differently from the
      others in displaying a phenomenon called rollover. G37A is, to our knowledge, the
      first reported case in which a single-site replacement causes rollover, while the
      wild type and all other known mutants of the same protein show typical two-state
      chevron plots. The best explanation is that the G37A mutation introduces a
      kinetic trap of the type described by Chan and Dill [(1998) Proteins 30, 2-33].
      In native BPTI, there is an unusual polar interaction between the ring of Tyr35
      and the backbone NH of Gly37. Our results suggest that the NH-aromatic
      interaction between residues 37 and 35 is important throughout folding in
      stabilizing native-like loop conformations and in preventing the flexible loops
      from being trapped in nonfunctional conformations during later stages of folding.

PMID- 11841215
TI  - A highly destabilizing mutation, G37A, of the bovine pancreatic trypsin inhibitor
      retains the average native conformation but greatly increases local flexibility.
AB  - A point mutation, G37A, on the surface of bovine pancreatic trypsin inhibitor
      (BPTI) destabilizes the protein by approximately 5 kcal/mol, which is very high
      for addition of one methyl group. In wild-type (WT) BPTI, Gly 37 HN is in an
      unusual NH-aromatic-NH network of interactions with the ring of Tyr 35 and the
      side chain HN of Asn 44. G37A was designed to disrupt this interaction, since the
      phi and psi backbone angles of G37 are not favorable for an amino acid containing
      a beta-carbon. Investigations of the structure and dynamics by NMR methods show
      that G37A retains the average WT structure. The NH-aromatic-NH interactions
      remain intact, as indicated by NOEs and the large upfield ring current shift
      (approximately 4 ppm) of A37 HN. The NMR structure, confirmed by molecular
      modeling calculations, requires phi and psi backbone angles that are highly
      destabilizing when alanine is in position 37. Although the average structure is
      essentially unchanged, the dynamics are altered dramatically. Many residues in
      the region of the mutation have increased flexibility, as probed by aromatic ring
      flip rates and native state hydrogen exchange. We conclude that a large fraction
      of the destabilization arises from maintaining A37 in a high-energy conformation.
      This suggests that disruption of the NH-aromatic-NH network is energetically very
      costly, and may involve other cooperatively linked interactions. The results
      illustrate the importance of the Gly-Gly sequence at positions 36 and 37 and the
      37 HN-35 aromatic interaction to the stability, folding, and dynamics of the
      BPTI.

PMID- 11841217
TI  - Conjugation of a magainin analogue with lipophilic acids controls hydrophobicity,
      solution assembly, and cell selectivity.
AB  - Our basic understanding of how to combat fungal infections has not kept pace with
      the recent sharp rise in life-threatening cases found particularly among immuno
      compromised individuals. Current investigations for new potential antifungal
      agents have focused on antimicrobial peptides, which are used as a cell-free
      defense mechanism in all organisms. Unfortunately, despite their high
      antibacterial activity, most of them are not active toward fungi, the reason of
      which is not clear. Here, we present a new approach to modify an antibacterial
      peptide, a magainin analogue, to display antifungal activity by its conjugation
      with lipophilic acids. This approach has the advantage of producing well-defined
      changes in hydrophobicity, secondary structure, and self-association. These
      modifications were characterized in solution at physiological concentrations
      using CD spectroscopy, tryptophan fluorescence, and analytical
      ultracentrifugation. In order of increasing hydrophobicity, the attachment to the
      magainin-2 analogue of (i) heptanoic acid results in a monomeric, unordered
      structure, (ii) undecanoic acid yields concentration-dependent oligomers of alpha
      helices, and (iii) palmitic acid yields concentration-independent alpha-helical
      monomers, a novel lipopeptide structure, which is resistant to proteolytic
      digestion. Membrane-lipopeptide interactions and the membrane-bound structures
      were studied using fluorescence and ATR-FTIR in PC/PE/PI/ergosterol (5/2.5/2.5/1,
      w/w) SUV, which constitute the major components of Candida albicans bilayers. A
      direct correlation was found between oligomerization of the lipopeptides in
      solution and potent antifungal activity. These results provide insight to a new
      approach of modulating hydrophobicity and self-assembly of antimicrobial peptides
      in solution, without altering the sequence of the peptidic chain. These studies
      also provide a general means of developing a new group of lipopeptide candidates
      as therapeutic agents against fungal infections.

PMID- 11841218
TI  - Functional role of "N" (nucleotide) and "P" (phosphorylation) domain interactions
      in the sarcoplasmic reticulum (SERCA) ATPase.
AB  - Experimental perturbations of the nucleotide site in the N domain of the SR Ca2+
      ATPase were produced by chemical derivatization of Lys492 or/and Lys515, mutation
      of Arg560 to Ala, or addition of inactive nucleotide analogue (TNP-AMP).
      Selective labeling of either Lys492 or Lys515 produces strong inhibition of
      ATPase activity and phosphoenzyme intermediate formation by utilization of ATP,
      while AcP utilization and reverse ATPase phosphorylation by Pi are much less
      affected. Cross-linking of the two residues with DIDS, however, drastically
      inhibits utilization of both ATP and AcP, as well as of formation of
      phosphoenzyme intermediate by utilization of ATP, or reverse phosphorylation by
      Pi. Mutation of Arg560 to Ala produces strong inhibition of ATPase activity and
      enzyme phosphorylation by ATP but has a much lower effect on enzyme
      phosphorylation by Pi. TNP-AMP increases the ATPase activity at low
      concentrations (0.1-0.3 microM), but inhibits ATP, AcP, and Pi utilization at
      higher concentration (1-10 microM). Cross-linking with DIDS and TNP-AMP binding
      inhibits formation of the transition state analogue with orthovanadate. It is
      concluded that in addition to the binding pocket delimited by Lys 492 and Lys515,
      Arg560 sustains an important and direct role in nucleotide substrate
      stabilization. Furthermore, the effects of DIDS and TNP-AMP suggest that
      approximation of N (nucleotide) and P (phosphorylation) domains is required not
      only for delivery of nucleotide substrate, but also to favor enzyme
      phosphorylation by nucleotide and nonnucleotide substrates, in the presence and
      in the absence of Ca2+. Domain separation is then enhanced by secondary
      nucleotide binding to the phosphoenzyme, thereby favoring its hydrolytic
      cleavage.

PMID- 11841219
TI  - Identification and characterization of allophenylnorstatine-based inhibitors of
      plasmepsin II, an antimalarial target.
AB  - Plasmepsin II is a key enzyme in the life cycle of the Plasmodium parasites
      responsible for malaria, a disease that afflicts more than 300 million
      individuals annually. Since plasmepsin II inhibition leads to starvation of the
      parasite, it has been acknowledged as an important target for the development of
      new antimalarials. In this paper, we identify and characterize high-affinity
      inhibitors of plasmepsin II based upon the allophenylnorstatine scaffold. The
      best compound, KNI-727, inhibits plasmepsin II with a K(i) of 70 nM and a 22-fold
      selectivity with respect to the highly homologous human enzyme cathepsin D. KNI
      727 binds to plasmepsin II in a process favored both enthalpically and
      entropically. At 25 degrees C, the binding enthalpy (DeltaH) is -4.4 kcal/mol and
      the entropic contribution (-TDeltaS) to the Gibbs energy is -5.56 kcal/mol.
      Structural stability measurements of plasmepsin II were also utilized to
      characterize inhibitor binding. High-sensitivity differential scanning
      calorimetry experiments performed in the absence of inhibitors indicate that, at
      pH 4.0, plasmepsin II undergoes thermal denaturation at 63.3 degrees C. The
      structural stability of the enzyme increases with inhibitor concentration in a
      manner for which the binding energetics of the inhibitor can quantitatively
      account. The effectiveness of the best compounds in killing the malaria parasite
      was validated by performing cytotoxicity assays in red blood cells infected with
      Plasmodium falciparum. EC50s ranging between 6 and 10 microM (3-6 microg/mL) were
      obtained. These experiments demonstrate the viability of the allophenylnorstatine
      scaffold in the design of powerful and selective plasmepsin inhibitors.

PMID- 11841220
TI  - Assignment of spectral substructures to pigment-binding sites in higher plant
      light-harvesting complex LHC-II.
AB  - The trimeric main light-harvesting complex (LHC-II) is the only antenna complex
      of higher plants of which a high-resolution 3D structure has been obtained
      (Kuhlbrandt, W., Wang, D., and Fujiyoshi, Y. (1994) Nature 367, 614-621) and
      which can be refolded in vitro from its components. Four different recombinant
      forms of LHC-II, each with a specific chlorophyll (Chl) binding site removed by
      site-directed mutagenesis, were refolded from heterologously overexpressed
      apoprotein, purified pigments, and lipid. Absorption spectra of mutant LHC-II
      were measured in the temperature range from 4 to 300 K and compared to likewise
      refolded wild-type complex and to native LHC-II isolated from pea chloroplasts.
      Chls at different binding sites have characteristic, well-defined absorption sub
      bands. Mixed occupation of binding sites with Chls a and b is not observed.
      Temperature-dependent changes of the mutant absorption spectra reveal a
      consistent shift of the major difference bands but an irregular behavior of minor
      bands. A model of the spectral substructure of LHC-II is proposed which accounts
      for the different absorption properties of the 12 individual Chls in the complex,
      thus establishing a first consistent correlation between the 3D structure of LHC
      II and its spectral properties. The spectral substructure is valid for
      recombinant and native LHC-II, indicating that both have the same spatial
      arrangement of Chls and that the refolded complex is fully functional.

PMID- 11841221
TI  - Mutants of the CuA site in cytochrome c oxidase of Rhodobacter sphaeroides: I.
      Spectral and functional properties.
AB  - To study the functional significance of the unusual bimetallic Cu(A) center of
      cytochrome c oxidase, the direct ligands of the Cu(A) center in subunit II of the
      holoenzyme were mutated. Two of the mutant forms, M263L and H260N, exhibit major
      changes in activity (10% and 1% of wild-type, respectively) and in near-infrared
      and EPR spectra, but metal analysis shows that both mutants retain two coppers in
      the Cu(A) center and both retain proton pumping activity. In M263L,
      multifrequency EPR studies indicate the coppers are still electronically coupled,
      while all the other metal centers in M263L appear unchanged, by visible, EPR, and
      FTIR spectroscopy. Nevertheless, heme a3 is very slow to reduce with cytochrome c
      or dithionite under stopped-flow and steady-state conditions. This effect appears
      to be secondary to the change in redox equilibrium between Cu(A) and heme a. The
      studies reported here and in Wang et al. [Wang, K., Geren, L., Zhen, Y., Ma, L.,
      Ferguson-Miller, S., Durham, B., and Millett, F. (2002) Biochemistry 41, 2298
      2304] demonstrate that altering the ligands of Cu(A) can influence the rate and
      equilibrium of electron transfer between Cu(A) and heme a, but that the native
      ligation state is not essential for proton pumping.

PMID- 11841222
TI  - Mutants of the CuA site in cytochrome c oxidase of Rhodobacter sphaeroides: II.
      Rapid kinetic analysis of electron transfer.
AB  - The function of the binuclear Cu(A) center in cytochrome c oxidase (CcO) was
      studied using two Rhodobacter sphaeroides CcO mutants involving direct ligands of
      the Cu(A) center, H260N and M263L. The rapid electron-transfer kinetics of the
      mutants were studied by flash photolysis of a cytochrome c derivative labeled
      with ruthenium trisbipyridine at lysine-55. The rate constant for intracomplex
      electron transfer from heme c to Cu(A) was decreased from 40000 s(-1) for wild
      type CcO to 16000 s(-1) and 11000 s(-1) for the M263L and H260N mutants,
      respectively. The rate constant for electron transfer from Cu(A) to heme a was
      decreased from 90000 s(-1) for wild-type CcO to 4000 s(-1) for the M263L mutant
      and only 45 s(-1) for the H260N mutant. The rate constant for the reverse
      reaction, heme a to Cu(A), was calculated to be 66000 s(-1) for M263L and 180 s(
      1) for H260N, compared to 17000 s(-1) for wild-type CcO. It was estimated that
      the redox potential of Cu(A) was increased by 120 mV for the M263L mutant and 90
      mV for the H260N mutant, relative to the potential of heme a. Neither mutation
      significantly affected the binding interaction with cytochrome c. These results
      indicate that His-260, but not Met-263, plays a significant role in electron
      transfer between Cu(A) and heme a.

PMID- 11841223
TI  - A structural investigation of the central chlorophyll a binding sites in the
      minor photosystem II antenna protein, Lhcb4.
AB  - Mutant proteins from light-harvesting complexes of higher plants may be obtained
      by expressing modified apoproteins in Escherichia coli, and reconstituting them
      in the presence of chlorophyll and carotenoid cofactors. This method has allowed,
      in particular, the engineering of mutant LHCs in which each of the residues
      coordinating the central Mg atoms of the chlorophylls was replaced by
      noncoordinating amino acids [Bassi, R., Croce, R., Cugini, D., and Sandona, D.
      (1999) Proc. Natl. Acad. Sci. U.S.A. 96, 10056-10061]. The availability of these
      mutants is of particular importance for determining the precise position of
      absorption bands for the different chlorophyll molecules, as well as the sequence
      of energy transfer events that occur within LHC complexes, provided that the
      structural impact of each mutation is precisely evaluated. Using resonance Raman
      spectroscopy, we have characterized the pigment-protein interactions in the minor
      photosystem II antenna protein, Lhcb4 (CP29), in which each of three of the four
      central chlorophyll a molecules has been removed by such mutations. By comparing
      the spectra of these mutants with those of the wild-type protein, the state of
      interaction of the carbonyl group, the coordination state of the central
      magnesium ion, and the dielectric constant (polarity) of the immediate
      environment in the binding pocket of the chlorophyll a molecule were defined for
      each cofactor binding site. In addition, the structural impact of the absence of
      one chlorophyll a molecule and the quality of protein folding were evaluated for
      each of these mutated polypeptides.

PMID- 11841224
TI  - Functional expression of human mitochondrial CYP11B2 in fission yeast and
      identification of a new internal electron transfer protein, etp1.
AB  - Mitochondrial cytochrome P450 enzymes play a crucial role in the steroid
      biosynthesis in human adrenals, catalyzing regio- and stereospecific
      hydroxylations. In search of a new model system for the study of these enzymes,
      we expressed the human CYP11B2 (aldosterone synthase, P450(aldo)) in fission
      yeast Schizosaccharomyces pombe. Analysis of the subcellular localization of the
      P450 enzyme by Western blot analysis, fluorescence microscopy, and electron
      microscopy demonstrated that the mitochondrial localization signal of the human
      protein is functional in S. pombe. The transformed yeasts show the inducible
      ability to convert in vivo considerable amounts of 11-deoxycortisol to cortisol
      and 11-deoxycorticosterone to corticosterone, 18-hydroxycorticosterone, and
      aldosterone, respectively. Although in mammalian cells, mitochondrial steroid
      hydroxylases depend for their activity on an electron transport chain that
      consists of two proteins, adrenodoxin and adrenodoxin reductase, no coexpression
      of these proteins is needed for efficient substrate conversion by intact fission
      yeast cells. Searching the fission yeast genome for adrenodoxin homologues, a
      gene was identified that codes for a protein with an amino terminal domain
      homologous to COX15 of Saccharomyces cerevisiae and a carboxy terminal ferredoxin
      domain. It was found that overexpression of this gene significantly enhances
      steroid hydroxylase activity of CYP11B2 expressing fission yeast cells. Moreover,
      the bacterially expressed ferredoxin domain of this protein can replace
      adrenodoxin in a reconstituted steroid hydroxylation assay and transfer electrons
      from adrenodoxin reductase to a mammalian or a bacterial cytochrome P450.
      Therefore, we suggest to name this protein etp1 (electron-transfer protein 1).

PMID- 11841225
TI  - Flash-induced FTIR difference spectra of the water oxidizing complex in
      moderately hydrated photosystem II core films: effect of hydration extent on S
      state transitions.
AB  - Differently hydrated films of photosystem II (PSII) core complexes from
      Synechococcus elongatus were prepared in a humidity-controlled infrared cell. The
      relative humidity was changed by a simple method of placing a different ratio of
      glycerol/water solution in the sealed cell. The extent of hydration of the PSII
      film was lowered as the glycerol ratio increased. FTIR difference spectra of the
      water oxidizing complex upon the first to sixth flashes were measured at 10
      degrees C using these hydrated PSII films. The FTIR spectra (1800-1200 cm(-1)) of
      the PSII films hydrated using 20% and 40% glycerol/water showed basically the
      same features as those of the core sample in solution [Noguchi, T., and Sugiura,
      M. (2001) Biochemistry 40, 1497-1502], and the prominent peaks exhibited clear
      period four oscillation patterns. These observations indicate that the S-state
      cycle properly functions in these hydrated samples. In the PSII films less
      hydrated, however, the efficiencies of S-state transitions decreased as the
      extent of hydration was lowered. This tendency was more significant in the S2 -->
      S3 and S3 --> S0 transitions than in the S1 --> S2 and S0 --> S1 transitions,
      indicating that the reactions or movements of water molecules are more strongly
      coupled with the former two transitions than the latter two. The implication of
      this observation was discussed in light of the water oxidizing mechanism
      especially in respect to the steps of substrate incorporation and proton release.
      Furthermore, in the OH stretching region (3800-3000 cm(-1)) of the first-flash
      spectrum, a differential signal was observed at 3618/3585 cm(-1), which was
      previously found in the S2/S1 spectrum of a frozen sample at 250 K and assigned
      to the water vibrations [Noguchi, T., and Sugiura, M. (2000) Biochemistry 39,
      10943-10949]. The fact that the signal appeared even in rather dehydrated PSII
      films at a physiological temperature (10 degrees C) supported the idea that this
      water is located in the close vicinity of the Mn cluster and directly involved in
      the water oxidizing reaction. The results also showed that moderate hydration of
      the PSII sample made the whole OH region measurable, escaping from absorption
      saturation by bulk water, and thus will be a useful technique to monitor the
      water reactions during the S-state cycle using FTIR spectroscopy.

PMID- 11841226
TI  - Proton and electron pathways in the bacterial nitric oxide reductase.
AB  - Electron- and proton-transfer reactions in bacterial nitric oxide reductase (NOR)
      have been investigated by optical spectroscopy and electrometry. In liposomes,
      NOR does not show any generation of an electric potential during steady-state
      turnover. This electroneutrality implies that protons are taken up from the same
      side of the membrane as electrons during catalysis. Intramolecular electron
      redistribution after photolysis of the partially reduced CO-bound enzyme shows
      that the electron transfer in NOR has the same pathway as in the heme-copper
      oxidases. The electron is transferred from the acceptor site, heme c, via a low
      spin heme b to the binuclear active site (heme b3/FeB). The electron-transfer
      rate between hemes c and b is (3 +/- 2) x 10(4) s(-1). The rate of electron
      transfer between hemes b and b3 is too fast to be resolved (>10(6) s(-1)). Only
      electron transfer between heme c and heme b is coupled to the generation of an
      electric potential. This implies that the topology of redox centers in NOR is
      comparable to that in the heme-copper cytochrome oxidases. The optical and
      electrometric measurements allow identification of the intermediate states formed
      during turnover of the fully reduced enzyme, as well as the associated proton and
      electron movement linked to the NO reduction. The first phase (k = 5 x 10(5) s(
      1)) is electrically silent, and characterized by the disappearance of absorbance
      at 433 nm and the appearance of a broad peak at 410 nm. We assign this phase to
      the formation of a ferrous NO adduct of heme b3. NO binding is followed by a
      charge separation phase (k = 2.2 x 10(5) s(-1)). We suggest that the formation of
      this intermediate that is not linked to significant optical changes involves
      movement of charged side chains near the active site. The next step creates a
      negative potential with a rate constant of approximately 3 x 10(4) s(-1) and a
      weak optical signature. This is followed by an electrically silent phase with a
      rate constant of 5 x 10(3) s(-1) leading to the last intermediate of the first
      turnover (a rate constant of approximately 10(3) s(-1)). The fully reduced enzyme
      has four electrons, enough for two complete catalytic cycles. However, the
      protons for the second turnover must be taken from the bulk, resulting in the
      generation of a positive potential in two steps. The optical measurements also
      verify two phases in the oxidation of low-spin hemes. Based on these results, we
      present mechanistic models of NO reduction by NOR. The results can be explained
      with a trans mechanism rather than a cis model involving FeB. Additionally, the
      data open up the possibility that NOR employs a P450-type mechanism in which only
      heme b3 functions as the NO binding site during turnover.

PMID- 11841227
TI  - Evidence of a tendency to self-association of the transmembrane domain of ErbB-2
      in fluid phospholipid bilayers.
AB  - The transmembrane domains of receptor tyrosine kinases are single-span helical
      structures suggested to participate directly in the formation of side-to-side
      receptor homodimers/homooligomers that modulate signal transduction.
      Transmembrane peptides from the class I receptor tyrosine kinase, ErbB-2, were
      examined directly by 2H NMR spectroscopy as a means of following such phenomena
      under the dynamic conditions that characterize fluid, fully hydrated bilayers of
      natural phospholipids. Appropriate peptides were expressed as 50-mers, containing
      the transmembrane domain of ErbB-2 plus contiguous stretches of amino acids from
      the cytoplasmic and extracellular domains. Deuterium probes were incorporated in
      place of 1H at a site within the helical intramembranous portion (the -CH3 side
      chain of Ala657), and the peptides were assembled into bilayers of 1-palmitoyl-2
      oleoylphosphatidylcholine (POPC) for study. An analogous peptide corresponding to
      the oncogenic variant characterized by a Val659-->Glu point mutation was also
      examined. At high peptide concentration, prominent spectral features could be
      assigned to rapidly rotating transmembrane monomers and to large oligomers
      rotating very slowly relative to a time scale of 10(-5) s. As peptide
      concentration was lowered, the latter feature was greatly reduced, and an
      additional population of mobile species became identifiable, consistent with the
      presence of homodimers and/or small oligomers. The defined nature of these latter
      spectral features suggests that preferred interaction sites exist on the
      peptides. The appearance of similar phenomena in the case of transmembrane
      peptides from both wild-type ErbB-2 and the transforming mutant argues for the
      involvement of additional factors in signal modulation, such as limitations
      normally imposed by the missing extramembranous portions.

PMID- 11841228
TI  - Six- to five-coordinate heme-nitrosyl conversion in cytochrome c' and its
      relevance to guanylate cyclase.
AB  - The 5-coordinate ferrous heme of Alcaligenes xylosoxidans cytochrome c' reacts
      with NO to form a 6-coordinate nitrosyl intermediate (lambdaSoret at 415 nm)
      which subsequently converts to a 5-coordinate nitrosyl end product (lambdaSoret
      at 395 nm) in a rate-determining step. Stopped-flow measurements at pH 8.9, 25
      degrees C, yield a rate constant for the formation of the 6-coordinate nitrosyl
      adduct, k(on) = (4.4 +/- 0.5) x 10(4) M(-1) x s(-1), which is 3-4 orders of
      magnitude lower than the values for other pentacoordinate ferrous hemes and is
      consistent with NO binding within the sterically crowded distal heme pocket.
      Resonance Raman measurements of the freeze-trapped 6-coordinate nitrosyl
      intermediate reveal an unusually high Fe-NO stretching frequency of 579 cm(-1),
      suggesting a distorted Fe-N-O coordination geometry. The rate of 6- to 5
      coordinate heme nitrosyl conversion is also dependent upon NO concentration, with
      a rate constant, k(6-5) = (8.1 +/- 0.7) x 10(3) M(-1) x s(-1), implying that an
      additional molecule of NO is required to form the 5c-NO adduct. Since
      crystallographic studies have shown that the 5-coordinate nitrosyl complex of
      cytochrome c' binds NO to the proximal (rather than distal) face of the heme, the
      NO dependence of the 6- to 5-coordinate NO conversion supports a mechanism in
      which the weakened His ligand, as well as the distally bound NO, is displaced by
      a second NO molecule which attacks and is retained in the proximal coordination
      position. The fact that a dependent 6- to 5-coordinate nitrosyl conversion has
      been previously reported for soluble guanylate cyclase suggests that the
      mechanism of Fe-His bond cleavage may be similar to that of cytochrome c' and
      strengthens the recent proposal that both proteins exhibit proximal NO binding in
      their 5-coordinate nitrosyl adducts.

PMID- 11841229
TI  - The sequence-specific association of the ETS domain of murine PU.1 with DNA
      exhibits unusual energetics.
AB  - PU.1 belongs to the ETS family of transcription factors whose DNA-binding domains
      recognize purine-rich sequences containing the consensus 5'-GGAA/T-3'. We have
      characterized the sequence-specific association of the ETS domain of murine PU.1
      to the lambdaB site of the Ig(lambda)2-4 enhancer as a function of temperature
      and pH by electrophoretic mobility shift, filter binding, and CD spectroscopy.
      From 0 to 25 degrees C, the dissociation equilibrium constant KD is, within
      experimental uncertainty, insensitive to temperature, and is only a weak function
      of temperature from 25 to 52 degrees C. van't Hoff analysis yielded a small value
      of DeltaCp = -2.1 kJ x mol(-1) x K(-1) in phosphate buffer, pH 7.4, containing
      250 mM Na+. KD also shows a weak dependence at 25 degrees C on pH from 6.7 to 9.0
      in phosphate, cacodylate, and Tris buffers that have disparate heats of
      ionization. The CD spectrum of the protein-DNA complex could be accounted for by
      a simple linear combination of the spectra of the free components throughout the
      binding temperature range. Structural calculations indicate that dehydration of
      solvent-accessible contact surfaces on the protein and DNA accounts for up to
      DeltaCp approximately -1 kJ x mol(-1) x K(-1). Taken together, these observations
      suggest that the hydrophobic effect and, in particular, coupled folding do not
      contribute significantly to the energetics of sequence-specific association. This
      is unusual with respect to other sequence-specific protein-DNA interactions for
      which significant enthalpic contributions and large negative heat capacities are
      commonly observed.

PMID- 11841230
TI  - Hepatitis C virus NS3 and simian virus 40 T antigen helicases displace
      streptavidin from 5'-biotinylated oligonucleotides but not from 3'-biotinylated
      oligonucleotides: evidence for directional bias in translocation on single
      stranded DNA.
AB  - Helicases are enzymes that use energy from nucleoside triphosphate hydrolysis to
      unwind double-stranded (ds) DNA, a process vital to virtually every phase of DNA
      metabolism. Helicases have been classified as either 5'-to-3' or 3'-to-5' on the
      basis of their ability to unwind duplex DNA adjacent to either a 5' or 3' single
      stranded (ss) DNA overhang. However, there has been debate as to whether this
      substrate preference is indicative of unidirectional translocation on ssDNA. We
      developed an assay that monitors the ability of a helicase to displace
      streptavidin from biotinylated oligonucleotides [Morris, P. D., and Raney, K. D.
      (1999) Biochemistry 38, 5164-5171]. Two helicases identified as having 5'-to-3'
      polarity displaced streptavidin from the 3'-end of biotinylated oligonucleotides
      but not from the 5'-end. We performed similar experiments using the 3'-to-5'
      helicases from the hepatitis C virus (NS3) and SV40 virus (SV40 T antigen). NS3
      and SV40 T antigen were able to displace streptavidin from a 5'-biotinylated
      oligonucleotide but not from a 3'-biotinylated oligonucleotide. NS3 and SV40 T
      antigen enhanced the spontaneous rate of dissociation of streptavidin from biotin
      340-fold and 1700-fold, respectively. The ssDNA binding protein, gp32, did not
      enhance dissociation of streptavidin from either end of an oligonucleotide. For
      NS3, the rate of displacement was faster from a 5'-biotinylated 60mer than from a
      5'-biotinylated 30mer. The strong directional bias in streptavidin displacement
      activity exhibited by each helicase is consistent with a directional bias in
      translocation on ssDNA. The dependence of the reaction with NS3 on the
      oligonucleotide length suggests that multiple NS3 monomers are necessary for
      optimal activity.

PMID- 11841231
TI  - Characterization of the propionyl-CoA synthetase (PrpE) enzyme of Salmonella
      enterica: residue Lys592 is required for propionyl-AMP synthesis.
AB  - The propionyl-CoA synthetase (PrpE) enzyme of Salmonella enterica catalyzes the
      first step of propionate catabolism, i.e., the activation of propionate to
      propionyl-CoA. The PrpE enzyme was purified, and its kinetic properties were
      determined. Evidence is presented that the conversion of propionate to propionyl
      CoA proceeds via a propionyl-AMP intermediate. Kinetic experiments demonstrated
      that propionate was the preferred acyl substrate (kcat/Km = 1644 mM(-1) x s(-1)).
      Adenosine 5'-propyl phosphate was a potent inhibitor of the enzyme, and
      inhibition kinetics identified a Bi Uni Uni Bi Ping Pong mechanism for the
      reaction catalyzed by the PrpE enzyme. Site-directed mutagenesis was used to
      change the primary sequence of the wild-type protein at positions G245A, P247A,
      K248A, K248E, G249A, K592A, and K592E. Mutant PrpE proteins were purified, and
      the effects of the mutations on enzyme activity were investigated. Both PrpEK592
      mutant proteins (K592A and K592E) failed to convert propionate to propionyl-CoA,
      and plasmids containing these alleles of prpE failed to restore growth on
      propionate of S. enterica carrying null prpE alleles on their chromosome. Both
      PrpEK592 mutant proteins converted propionyl-AMP to propionyl-CoA, suggesting
      residue K592 played no discernible role in thioester bond formation. To the best
      of our knowledge, these mutant proteins are the first acyl-CoA synthetases
      reported that are defective in adenylation activity.

PMID- 11841232
TI  - Characterization of a novel endo-beta-galactosidase specific for releasing the
      disaccharide GlcNAc alpha 1-->4Gal from glycoconjugates.
AB  - In contrast to the beta-linked GlcNAc, the alpha-linked GlcNAc has not been
      commonly found in glycoconjugates. We have recently revealed the presence of an
      unusual endo-beta-galactosidase (Endo-beta-Gal(GnGa)) in Clostridium perfringens
      capable of releasing GlcNAcalpha1-->4Gal from glycans expressed in the gastric
      mucous cell-type mucin [Ashida, H., Anderson, K., Nakayama, J., Maskos, K., Chou,
      C.-W., Cole, R. B., Li, S.-C., and Li, Y.-T. (2001) J. Biol. Chem. 276, 28226
      28232]. To characterize Endo-beta-Gal(GnGa), we have cloned its gene, gngC, from
      the genomic DNA library prepared from C. perfringens ATCC10543. The gene encodes
      420 amino acid residues including a 17-residue signal peptide at the N-terminus.
      Using pUC18, we were able to prepare 25 mg of the fully active and pure
      recombinant Endo-beta-Gal(GnGa) from 1 L of Escherichia coli DH5alpha culture,
      which was 170 times higher than that produced by the original clostridial strain.
      Endo-beta-Gal(GnGa) shares a low but significant sequence similarity with two
      other endo-beta-galactosidases (16-21% amino acid identity). It also shows some
      similarity with bacterial 1,3-1,4-beta-glucan 4-glucanohydrolases of the
      glycoside hydrolase family 16. Endo-beta-Gal(GnGa) was found to contain the
      EXDX(X)E sequence (Glu-168 to Glu-173), that has been identified as the catalytic
      motif of families 16 and 7 retaining glycoside hydrolases. We have used site
      directed mutagenesis to show that Glu-168 and Glu-173 were essential for the Endo
      beta-Gal(GnGa) activity. By NMR spectroscopy, Endo-beta-Gal(GnGa) was found to
      act as a retaining enzyme.

PMID- 11841233
TI  - Temperature- and pressure-induced unfolding and refolding of ubiquitin: a static
      and kinetic Fourier transform infrared spectroscopy study.
AB  - Temperature- and pressure-induced denaturation of the protein ubiquitin was
      investigated using FT-IR spectroscopy. On the basis of IR spectral parameters,
      different states are distinguished and a pressure/temperature-stability diagram
      of the protein has been determined. The evolution of the secondary structures
      with temperature illustrates that the band intensities of disordered structures
      decrease at the expense of the formation of intermolecular beta-sheets at 83
      degrees C, pD 7, and ambient pressure, with the population of intramolecular beta
      sheets and alpha-helices remaining essentially unchanged. At ambient temperature
      (T = 21 degrees C) and pD 7, ubiquitin denatures at 5.4 kbar. Contrary to other
      proteins studied so far, features of secondary structure of ubiquitin remain
      distinct at high pressure, suggesting that part of this small protein rearranges
      and does not unfold to disordered structures. The secondary structural changes
      during compression and decompression are fully reversible, and no aggregation
      occurs. With corresponding measurements of the pressure-induced denaturation of
      ubiquitin at different temperatures, a p/T-stability diagram of ubiquitin could
      be obtained. Furthermore, kinetic FT-IR measurements were carried out using the
      pressure-jump relaxation technique. The denaturation process is shown to occur on
      a time scale which is about twice as long as that of the renaturation process,
      and both processes are much slower than the unfolding-refolding kinetics observed
      at ambient pressure.

PMID- 11841234
TI  - Strand-specific binding of RPA and XPA to damaged duplex DNA.
AB  - The nucleotide excision repair (NER) pathway is a major pathway used to repair
      bulky adduct DNA damage. Two proteins, xeroderma pigmentosum group A protein
      (XPA) and replication protein A (RPA), have been implicated in the role of DNA
      damage recognition in the NER pathway. The particular manner in which these two
      damage recognition proteins align themselves with respect to a damaged DNA site
      was assessed using photoreactive base analogues within specific DNA substrates to
      allow site-specific cross-linking of the damage recognition proteins. Results of
      these studies demonstrate that both RPA and XPA are in close proximity to the
      adduct as measured by cross-linking of each protein directly to the platinum
      moiety. Additional studies demonstrate that XPA contacts both the damaged and
      undamaged strands of the duplex DNA. Direct evidence is presented demonstrating
      preferential binding of RPA to the undamaged strand of a duplex damaged DNA
      molecule.

PMID- 11841235
TI  - Novel interactions of Saccharomyces cerevisiae type 1 protein phosphatase
      identified by single-step affinity purification and mass spectrometry.
AB  - The catalytic subunit of Saccharomyces cerevisiae type 1 protein phosphatase
      (PP1(C)) is encoded by the essential gene GLC7 and is involved in regulating
      diverse cellular processes. To identify potential regulatory or targeting
      subunits of yeast PP1(C), we tagged Glc7p at its amino terminus with protein A
      and affinity-purified Glc7p protein complexes from yeast. The purified proteins
      were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS
      PAGE) and identified by peptide mass fingerprint analysis using matrix-assisted
      laser desorption/ionization (MALDI) mass spectrometry. To confirm the accuracy of
      our identifications, peptides from some of the proteins were also sequenced using
      high-performance liquid chromatography (HPLC) coupled to tandem mass
      spectrometry. Only four of the Glc7p-associated proteins that we identified
      (Mhp1p, Bni4p, Ref2p, and Sds22p) have previously been shown to interact with
      Glc7p, and multiple components of the CPF (cleavage and polyadenylation factor)
      complex involved in messenger RNA 3'-end processing were present as major
      components in the Glc7p-associated protein fraction. To confirm the interaction
      of Glc7p with this complex, we used the same approach to purify and characterize
      the components of the yeast CPF complex using protein A-tagged Pta1p. Six known
      components of the yeast (CPF) complex, together with Glc7p, were identified among
      the Pta1p-associated polypeptides using peptide mass fingerprint analysis. Thus
      Glc7p is a novel component of the CPF complex and may therefore be involved
      regulating mRNA 3'-end processing.

PMID- 11841236
TI  - Rhodanese can partially refold in its GroEL-GroES-ADP complex and can be released
      to give a homogeneous product.
AB  - Molecular chaperones GroEL and GroES facilitate reactivation of denatured
      rhodanese which folds poorly unless the process is assisted. The present work
      tests the hypothesis that more extensively unfolded forms of rhodanese bind
      tighter than those forms that appear later in the folding pathway. The study of
      the interaction of different urea-induced forms of rhodanese with GroEL suggests
      that species preceding the domain folded form bind directly and productively to
      GroEL. Rhodanese partially folds while in the GroEL-GroES-ADP complex, but it
      does not significantly reach an active state. Partially folded rhodanese can be
      released from the GroEL-GroES-ADP complex by subdenaturing concentrations of urea
      as a homogeneous species that is committed to fold to the native conformation
      with little or no partitioning to the aggregated state. Dilution of denatured
      rhodanese to the same final concentration gives less active enzyme and
      significant aggregation. Urea denaturation studies show that active rhodanese
      released from complexes behaves identically to native enzyme, while spontaneously
      folded rhodanese has a different stability. These results are interpreted using a
      previously proposed model based on studies of unassisted rhodanese folding
      [Gorovits, B. M., McGee, W. A., and Horowitz, P. M. (1998) Biochim. Biophys. Acta
      1382, 120-128. Panda, M., Gorovits, B. M., and Horowitz, P. M. (2000) J. Biol.
      Chem. 275, 63-70].

PMID- 11841237
TI  - Tryptophan interactions in bacteriorhodopsin: a heteronuclear solid-state NMR
      study.
AB  - The bulky and amphiphilic nature of tryptophan residues makes them particularly
      interesting components of proteins. In bacteriorhodopsin, four of the eight
      tryptophan residues are in the active site, forming parts of the retinal binding
      pocket. In this work, we use solid-state NMR to study the interactions of the
      tryptophan residues in wild-type bacteriorhodopsin, in the resting state, and in
      critical intermediates of the proton-motive photocycle. The range of the chemical
      shifts of the indole nitrogens suggests that all eight of them are hydrogen
      bonded. Using difference spectroscopy, we isolate several changes in these
      hydrogen bonds in the early and late M states. As found earlier for the peptide
      backbone, some perturbations found in the early M state relax in the transition
      to the late M state while new perturbations arise. Interestingly, Rotational Echo
      DOuble Resonance (REDOR) difference spectroscopy of [20-13C]retinal,[indole
      15N]Trp-bR shows that indole of Trp182 is not involved in the significant
      hydrogen bond perturbations. We also use REDOR to measure dipolar interactions in
      [20-13C]retinal,[indole-15N]Trp-bR, and thereby determine the distance between
      the C20 of retinal and the indole nitrogen of Trp182. The internuclear distance
      changes only slightly from the light-adapted state (3.36 +/- 0.2 A) to the early
      M state (3.16 +/- 0.4 A).

PMID- 11841238
TI  - Gastric H/K-ATPase liberates two moles of Pi from one mole of phosphoenzyme
      formed from a high-affinity ATP binding site and one mole of enzyme-bound ATP at
      the low-affinity site during cross-talk between catalytic subunits.
AB  - The maximum amount of acid-stable phosphoenzyme (E32P)/mol of alpha chain of pig
      gastric H/K-ATPase from [gamma-32P]ATP (K(1/2) = 0.5 microM) was found to be
      approximately 0.5, which was half of that formed from 32P(i) (K(1/2) = 0.22 mM).
      The maximum 32P binding for the enzyme during turnover in the presence of [gamma
      32P]ATP or [alpha-32P]ATP was due to 0.5 mol of E32P + 0.5 mol of an acid-labile
      enzyme-bound [gamma-32P]ATP (EATP) or 0.5 mol of an acid-labile enzyme-bound
      [alpha-32P]ATP, respectively. The K(1/2) for EATP formation in both cases was
      0.12 approximately 0.14 mM. The turnover number of the enzyme (i.e., the H+
      ATPase activity/(EP + EATP)) was very close to the apparent rate constants for EP
      breakdown and P(i) liberation, both of which decreased with increasing
      concentrations of ATP. The ratio of the amount of P(i) liberated to that of EP
      that disappeared increased from 1 to approximately 2 with increasing
      concentrations of ATP (i.e., equal amounts of EP and EATP exist, both of which
      release phosphate in the presence of high concentrations of ATP). This represents
      the first direct evidence, for the case of a P-type ATPase, in which 2 mol of
      P(i) liberation occurs simultaneously from 1 mol of EP for half of the enzyme
      molecules and 1 mol of EATP for the other half during ATP hydrolysis. Each
      catalytic alpha chain is involved in cross-talk, thus maintaining half-site
      phosphorylation and half-site ATP binding which are induced by high- and low
      affinity ATP binding, respectively, in the presence of Mg2+.

PMID- 11841239
TI  - The carboxyl terminus of the epsilon subunit of the chloroplast ATP synthase is
      exposed during illumination.
AB  - The epsilon subunit of the chloroplast ATP synthase is an inhibitor of activity
      of the enzyme. Recombinant forms of the epsilon subunit from spinach chloroplasts
      lacking the last 10, 32, or 45 amino acids were immobilized onto activated
      Sepharose. A polyclonal antiserum raised against the epsilon subunit was passed
      over these immobilized protein columns, and the purified antibodies which were
      not bound recognized the portions of the epsilon subunit missing from the
      recombinant form present on the column. The full polyclonal antiserum can strip
      the epsilon subunit from the ATP synthase in illuminated thylakoid membranes
      [Richter, M. L., and McCarty, R. E. (1987) J. Biol. Chem. 262, 15037-15040].
      Exposure of illuminated thylakoid membranes to antibodies recognizing the last 32
      amino acids of the epsilon subunit collapses the proton gradient and hinders ATP
      synthesis with similar efficiency as the full polyclonal preparation. These
      results indicate that antibodies against the last 32 amino acids of the epsilon
      subunit are capable of stripping the subunit from the ATP synthase in illuminated
      membranes. Neither of these effects was seen when the membranes were exposed to
      the antibodies in the dark. This is direct evidence that the chloroplast ATP
      synthase undergoes a conformational shift during its activation by the
      electrochemical proton gradient which specifically alters the conformation of the
      carboxyl-terminal domain of the epsilon subunit from protected to solvent
      exposed. The relation between this shift and activation of the enzyme by the
      electrochemical proton gradient is discussed.

PMID- 11841241
TI  - 11 Beta-hydroxysteroid dehydrogenase type 1 from human liver: dimerization and
      enzyme cooperativity support its postulated role as glucocorticoid reductase.
AB  - 11Beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD 1) is a microsomal enzyme
      that catalyzes the reversible interconversion of receptor-active 11-hydroxy
      glucocorticoids (cortisol) to their receptor-inactive 11-oxo metabolites
      (cortisone). However, the physiological role of 11beta-HSD 1 as prereceptor
      control device in regulating access of glucocorticoid hormones to the
      glucocorticoid receptor remains obscure in light of its low substrate affinities,
      which is in contrast to low glucocorticoid plasma levels and low Kd values of the
      receptors to cortisol. To solve this enigma, we performed detailed kinetic
      analyses with a homogeneously purified 11beta-HSD 1 from human liver. The
      membrane-bound enzyme was successfully obtained in an active state by a
      purification procedure that took advantage of a gentle solubilization method as
      well as providing a favorable detergent surrounding during the various
      chromatographic steps. The identity of purified 11beta-HSD 1 was proven by
      determination of enzymatic activity, N-terminal amino acid sequencing, and
      immunoblot analysis. By gel-permeation chromatography we could demonstrate that
      11beta-HSD 1 is active as a dimeric enzyme. The cDNA for the enzyme was cloned
      from a human liver cDNA library and shown to be homologous to that previously
      characterized in human testis. Interestingly, 11beta-HSD 1 exhibits Michaelis
      Menten kinetics with cortisol and corticosterone (11beta-dehydrogenation
      activity) but cooperative kinetics with cortisone and dehydrocorticosterone (11
      oxoreducing activity). Accordingly, this enzyme dynamically adapts to low
      (nanomolar) as well as to high (micromolar) substrate concentrations, thereby
      providing the fine-tuning required as a consequence of great variations in
      circadian plasma glucocorticoid levels.

PMID- 11841240
TI  - Stopped-flow analysis on anion binding to blue-form halorhodopsin from
      Natronobacterium pharaonis: comparison with the anion-uptake process during the
      photocycle.
AB  - Pharaonis halorhodopsin (phR), the light-driven chloride ion pump from
      Natronobacterium pharaonis with C-terminal histidine tag, was expressed in
      Escherichia coli cells. The protein was solubilized with 0.1% n-dodecyl beta-D
      maltopyranoside and purified with a nickel column. Removal of Cl- from the medium
      yields blue phR (phR(blue)) that has lost Cl- near the chromophore. Addition of
      Cl- converts phR(blue) to a red-shifted Cl--bound form (phR(Cl)). Circular
      dichroic spectra of phR(blue) and phR(Cl) exhibited a bilobe in the visual
      region, indicating specific oligomerization of the phR monomers. The order of
      anion concentration which induced a shift from phR(blue) to phR(X) was Br- < Cl-
      < NO3- < N3-, which was the same as in the case of phR purified from N. pharaonis
      membranes. Chloride binding kinetics was measured by time-resolved absorption
      changes with stopped-flow rapid mixing. Rates of Cl- binding consisted of fast
      and slow components, and the amplitude of the fast component was about 90% of the
      total changes. The rate constant of the fast component at 100 mM NaCl at 25
      degrees C was 260 s(-1) with an apparent activation energy of 35 kJ/mol. These
      values are in good agreement with the process of Cl- uptake in the photocycle (O 
      -> hR' reaction) reported previously [Varo et al. (1995) Biochemistry 34, 14500
      14507]. In addition, the Cl- concentration dependence on both rates was similar
      to each other. These observations suggest that the O-intermediate is similar to
      phR(blue) and that Cl- uptake during the photocycle may be ruled by a passive
      process.

PMID- 11841242
TI  - Iron nitrosyl hemoglobin formation from the reactions of hemoglobin and
      hydroxyurea.
AB  - Hydroxyurea represents an approved treatment for sickle cell anemia and acts as a
      nitric oxide donor under oxidative conditions in vitro. Electron paramagnetic
      resonance spectroscopy shows that hydroxyurea reacts with oxy-, deoxy-, and
      methemoglobin to produce 2-6% of iron nitrosyl hemoglobin. No S-nitrosohemoglobin
      forms during these reactions. Cyanide and carbon monoxide trapping studies reveal
      that hydroxyurea oxidizes deoxyhemoglobin to methemoglobin and reduces
      methemoglobin to deoxyhemoglobin. Similar experiments reveal that iron nitrosyl
      hemoglobin formation specifically occurs during the reaction of hydroxyurea and
      methemoglobin. Experiments with hydroxyurea analogues indicate that nitric oxide
      transfer requires an unsubstituted acylhydroxylamine group and that the reactions
      of hydroxyurea and deoxy- and methemoglobin likely proceed by inner-sphere
      mechanisms. The formation of nitrate during the reaction of hydroxyurea and
      oxyhemoglobin and the lack of nitrous oxide production in these reactions suggest
      the intermediacy of nitric oxide as opposed to its redox form nitroxyl. A
      mechanistic model that includes a redox cycle between deoxyhemoglobin and
      methemoglobin has been forwarded to explain these results that define the
      reactivity of hydroxyurea and hemoglobin. These direct nitric oxide producing
      reactions of hydroxyurea and hemoglobin may contribute to the overall
      pathophysiological properties of this drug.

PMID- 11841244
TI  - Protein N-glycosylation along the secretory pathway: relationship to organelle
      topography and function, protein quality control, and cell interactions.

PMID- 11841245
TI  - Glycosylation and the complement system.

PMID- 11841246
TI  - Structural investigations of glycoconjugates at high sensitivity.

PMID- 11841247
TI  - Conformational studies of oligosaccharides and glycopeptides: complementarity of
      NMR, X-ray crystallography, and molecular modelling.

PMID- 11841248
TI  - Thermodynamic studies of lectin-carbohydrate interactions by isothermal titration
      calorimetry.

PMID- 11841249
TI  - The emerging significance of O-GlcNAc in cellular regulation.

PMID- 11841250
TI  - Chemical diversity in the sialic acids and related alpha-keto acids: an
      evolutionary perspective.

PMID- 11841251
TI  - Recent advances in the synthesis of sialic acid derivatives and sialylmimetics as
      biological probes.

PMID- 11841252
TI  - Carbohydrate-based mimetics in drug design: sugar amino acids and carbohydrate
      scaffolds.

PMID- 11841253
TI  - Recent developments of transition-state analogue glycosidase inhibitors of non
      natural product origin.

PMID- 11841254
TI  - The cluster glycoside effect.

PMID- 11841256
TI  - An unexpected bispericyclic transition structure leading to 4+2 and 2+4
      cycloadducts in the endo dimerization of cyclopentadiene.
AB  - The stereospecific endo dimerization of cyclopentadiene takes place through an
      asynchronous and symmetrical bispericyclic transition structure, which shows a
      merging of the 4+2 and 2+4 cycloaddition paths. The shape of the transition
      structure testifies to the presence of attractive Salem/Houk secondary orbital
      interactions assisting the endo approach.

PMID- 11841255
TI  - Synthesis of glycoproteins.

PMID- 11841257
TI  - The fate of sulfur-bound hydrogen on formation of self-assembled thiol monolayers
      on gold: (1)H NMR spectroscopic evidence from solutions of gold clusters.
AB  - It is demonstrated that thiols can adsorb to gold without losing hydrogen.
      Dodecyl sulfide-capped gold clusters have been prepared and subjected to ligand
      exchange reactions in perdeuterated benzene by addition of dodecanethiol and
      subsequently dodecyl disulfide. It is shown by 1H NMR spectroscopy that
      dodecanethiol molecules are readily taken up as ligands producing characteristic
      broad signals corresponding to the alpha-methylene and S-H protons, with chemical
      shifts close to those found for thiol in solution; these signals are absent in
      spectra of thiolate-capped clusters. Addition of excess disulfide to such
      clusters capped with both dialkyl sulfides and thiols leads to the appearance of
      sharp signals for free dialkyl sulfide and intact thiol. Amounts of thiols up to
      50% of the ligand shell are, however, taken up by the clusters under rapid and
      irreversible loss of hydrogen.

PMID- 11841258
TI  - Phenanthroline complexes bearing fused dipyrrolylquinoxaline anion recognition
      sites: efficient fluoride anion receptors.
AB  - Novel anion recognition host molecules, tris-1,10-phenanthroline cobalt(III) and
      bis-2,2'-bipyridine mono-1,10-phenanthroline ruthenium(II) complexes bearing
      fused dipyrrolylquinoxaline moieties have been synthesized. As determined by UV
      vis spectroscopic and electrochemical studies, these metal complexes bind
      fluoride with high affinity in polar media both in absolute terms and relative to
      the metal-free phenanthroline dipyrrolylquinozaline precursor from which they are
      derived (fluoride is bound to the tris-1,10-phenanthroline cobalt(III)
      dipyrrolylquinoxaline system with a 1:1 binding constant of 54 000 M-1 in DMSO).
      The large observed binding constants are ascribed to two factors, (i) the
      presence of a phenanthroline-coordinated cationic charge that decreases the
      electron density on the pyrrole NH protons and (ii) pure electrostatic effects.

PMID- 11841259
TI  - Isolation of monomeric Mn(III/II)-H and Mn(III)-complexes from water: evaluation
      of O-H bond dissociation energies.
AB  - The syntheses and properties of the monomeric [MnIII/IIH31(OH)]-/2- and
      [MnIIIH31(O)]2- complexes are reported, where [H31]3- is the tripodal ligand
      tris[(N'-tert-butylureaylato)-N-ethyl)]aminato. Isotope-labeling studies with
      H218O confirmed that water is the source of the terminal oxo and oxygen in the
      hydroxo ligand. The molecular structures of the [MnIIH31(OH)]2- and
      [MnIIIH31(O)]2- complexes were determined by X-ray diffraction methods and show
      that each complex has trigonal bipyramidal coordination geometry. The MnIII-O
      distance in [MnIIIH31(O)]2- is 1.771(4) A, which is lengthened to 2.059(2) A in
      [MnIIH31(OH)]2-. Structural studies also show that [H31]3- provides a hydrogen
      bond cavity that surrounds the MnIII-O(H) units. Using a thermodynamic approach,
      which requires pKa and redox potentials, bond dissociation energies of 77(4) and
      110(4) kcal/mol were calculated for [MnIIH31(O-H)]2- and [MnIIIH31(O-H)]-,
      respectively. The calculated value of 77 kcal/mol for the [MnIIH31(O-H)]2-
      complex is supported by the ability of [MnIIIH31(O)]2- complex to cleave C-H
      bonds with bond energies of <80 kcal/mol.

PMID- 11841260
TI  - A new fluorescent biosensor for inositol trisphosphate.
AB  - An intracellular second messenger d-myo-inositol-1,4,5-trisphosphate (IP3) is a
      key biological signaling molecule that controls the cellular Ca2+ concentration.
      We report the preparation and evaluation of a functionalized protein-based sensor
      for IP3 by exploring the selective IP3 binding properties of pleckstrin homology
      (PH) domain. Signal transduction is imparted to the protein by mutation of
      proximal residues to cysteine and then alkylation of the active site by various
      fluorophore derivatives. This creates functionalized proteins that show
      micromolar affinity for IP3, reasonably strong fluorescence emission, and
      wavelength changes in the fluorophore and selectivity higher than the original PH
      domain among different inositol phosphate derivatives.

PMID- 11841261
TI  - Gemini-induced columnar jointing in vitreous ice. Cryo-HRSEM as a tool for
      discovering new colloidal morphologies.
AB  - A gemini surfactant is able to promote columnar jointing in vitreous ice where
      long pillars, often of hexagonal cross section, are formed. This jointing is
      visible by cryo-high-resolution scanning electron microscopy (cryo-HRSEM), in
      which colloidal suspensions in bulk water are cooled rapidly in liquid ethane,
      thereby avoiding the potential artifacts with other types of EM. The jointing is
      proposed to arise from a new type of colloidal morphology where the surfactant
      self-assembles into hexagonal columns. Evidence for this mechanism comes from a
      cryo-HRSEM photo of an ice-free hexagonal "skeleton" composed of surfactant. Cryo
      HRSEM, a method that is just beginning to realize its potential, would seem to
      have a promising future in the discovery of additional and as yet unimagined
      colloidal structures.

PMID- 11841262
TI  - Ordered morphologies in polymeric films produced by replication of convection
      patterns.
AB  - A new strategy for producing ordered polymeric films is proposed, which employs
      replication of interfacial instabilities. In the first step, a thin film of a
      monomeric fluid is brought in contact with a nonpolymerizable template layer of
      poly(dimethylsiloxane), and surface tension-driven convection is induced in the
      template liquid. In the second stage, Benard cells replicated in the monomeric
      layer by a viscous drug are trapped in the solid state by UV-induced
      polymerization. Following this step, the template fluid is removed. The
      topographic patterns "frozen" in the polymeric film have lateral and vertical
      periodicity determined by the properties of the template fluid.

PMID- 11841263
TI  - Reactions of zirconacyclopentadienes with C [double bond] ), C [double bond] N,
      and N [double bond] N moieties with electron-withdrawing groups: formation of six
      membered heterocycles.
AB  - Reactions of zirconacyclopentadienes with diethyl ketomalonate gave alpha-pyrans
      in excellent yields in the presence of BiCl3. In the absence of BiCl3,
      zirconacyclopentadienes did not react with diethyl ketomalonate.
      Tetraphenylzirconacyclopentadiene reacted with diethyl ketomalonate in the
      presence of BiCl3 to give a ring-opening product, dienolic ether, in 53% yield.
      The structures of the alpha-pyran prepared from
      diethyldiphenylzirconacyclopentadiene and the ring-opening product were
      determined by X-ray analysis. When oximinosulfonate was added to
      tetraethylzirconacyclopentadiene in THF at -78 degrees C, 3,4,5,6
      tetraethylpyridine-2-carbonitrile was obtained in 95% yield within 10 min. The
      structure of the product was confirmed by X-ray analysis. When
      tetraethylzirconacyclopentadiene was treated with azodicarboxylate in the
      presence of 2 equiv of CuCl at -78 degrees C, 1,2-dialkoxycarbonyl-3,4,5,6
      tetraethyl-1,2-dihydropyridazine derivatives were obtained. The structure of one
      of dihydropyridazine was also confirmed by X-ray analysis.

PMID- 11841264
TI  - Bilayer sample for fast or slow magic angle oriented sample spinning solid-state
      NMR spectroscopy.
AB  - An alternative setup for Magic Angle Oriented Spinning Spectroscopy is proposed.
      Samples were prepared by orienting lipid bilayers onto polymer films, which were
      wrapped into a spiral so as to fit into 4 or 7 mm MAS rotors. This geometry
      resulted in narrow line widths and a higher upper spinning limit when compared to
      the conventional MAOSS setup with stacked glass plates. Whereas orientational
      information was extracted from low spinning spectra, fast spinning will be
      applicable to high-resolution multidimensional NMR pulse sequences.

PMID- 11841265
TI  - Optimizing the least nucleophilic anion. A new, strong methyl(+) reagent.
AB  - The icosahedral carborane anions H-CB11X6H5- (X = Cl, Br, I) are among the most
      inert, least coordinating, and least basic anions known. These properties are
      enhanced by 2,3,4,5,6-pentamethylation with methyl triflate. The resulting
      anions, H-CB11X6Me5-, are more inert than their unmethylated precursors, have
      improved NMR handles, and their salts have higher solubility in low dielectric
      media. They sustain superacidity in H(H-CB11X6Me5). Protonated benzene has been
      isolated and characterized by X-ray crystallography, moving Wheland intermediates
      from the status of spectroscopically observable transients to weighable reagents.
      The new anions sustain extreme Lewis acidity in silylium ion-like R3Si(H
      CB11X6Me5) species. Treatment of Et3Si(H-CB11Br6Me5) with methyl triflate leads
      to a new methyl+ reagent CH3(H-CB11Br6Me5) that is more potent than methyl
      triflate. It methylates benzene without heating or acid catalysis to give the
      toluenium ion. The H-CB11X6Me5- anions come as close as any to the concept of a
      univeral weakly coordinating anion and, with cheaper starting materials now
      available, promise to become specialty chemicals of wide usage.

PMID- 11841266
TI  - Room temperature solution synthesis of alkyl-capped tetrahedral shaped silicon
      nanocrystals.
AB  - We report the room temperature solution synthesis of alkyl protected silicon
      nanocrystals. The nanocrystals are of unusually uniform tetrahedral morphology
      and of a limited size distribution. The nanocrystals were characterized by
      transmission and scanning electron microscopy as well as atomic force microscopy.

PMID- 11841268
TI  - Peptide pinwheels.
AB  - Electrospraying a mixture of Ac-(GA)7K and Ac-A(GA)7K (Ac = acetyl, G = glycine,
      A = alanine, and K = lysine) peptides produces strong signals for unsolvated
      dimers and trimers. The conformations of these multimers have been examined with
      use of ion mobility measurements in conjunction with molecular dynamics
      simulations. The results suggest that the trimers adopt a pinwheel arrangement of
      helices with the C-termini tethered together by the protonated lysine side chain
      from one peptide interacting with the C-terminus of a neighboring helix. This
      arrangement leads to a cooperative electrostatic stabilization of all the helices
      through the interaction of the combined charge with the helix dipoles. The dimer
      adopts a related V-shaped arrangement of helices which is also cooperatively
      stabilized.

PMID- 11841267
TI  - The direct detection of a hydrogen bond in the solid state by NMR through the
      observation of a hydrogen-bond mediated (15)N [bond] (15)N J coupling.
AB  - A new method for detecting hydrogen bonds in the solid state is presented. Using
      two-dimensional NMR correlation experiments, it is shown that a hydrogen-bond
      mediated J coupling can be observed in a powder under magic-angle spinning
      conditions, even though the J coupling is 2 orders of magnitude smaller than the
      dominant anisotropic interactions encountered in solid-state NMR. Specifically,
      the observation of a pair of peaks in a two-dimensional 15N-15N solid-state
      INADEQUATE experiment due to two nitrogens that have no covalent connectivity is
      attributed to the presence of a J coupling across a linking hydrogen bond.

PMID- 11841269
TI  - Synthesis of mesoporous silicas of controlled pore wall thickness and their
      replication to ordered nanoporous carbons with various pore diameters.
AB  - A synthesis strategy for the systematic control of the pore wall thickness has
      been developed for the mesoporous silicas with 2-D hexagonal order using ionic
      and nonionic surfactant mixtures. The mesoporous silicas have been used as
      templates for the synthesis of 2-D hexagonally ordered mesoporous carbons with
      controlled pore diameters. The synthesis strategy and results are useful not only
      for tailoring the properties of the mesoporous materials but also for extending
      our insights into the synthesis mechanism.

PMID- 11841270
TI  - The first halogen-substituted cyclotrigermenes: a unique halogen walk over the
      three-membered ring skeleton and facial stereoselectivity in the Diels-Alder
      reaction.
AB  - Dark red crystals of the halogen-substituted cyclotrigermenes [(tBu3Si)3Ge3X; X =
      Cl, Br, I] were obtained in good yields by the reaction of [(tBu3Si)3Ge3]+.TTFPB-
      (TTFPB- = tetrakis(2,3,5,6-tetrafluorophenyl)borate) with potassium halides (KCl,
      KBr, or KI) in diethyl ether. The crystal structures of the halogen-substituted
      cyclotrigermenes reveal a cis-bent Ge=Ge double bond, caused by the introduction
      of the electronegative halogen atom on the sp3 germanium atom of cyclotrigermene.
      In solution, an intramolecular halogen migration over the three-membered ring
      skeleton was observed. Facial stereoselectivity in the Diels-Alder reaction of
      new cyclotrigermenes with 2,3-dimethyl-1,3-butadiene is also reported.

PMID- 11841271
TI  - A site-specific low-enrichment (15)N,(13)C isotope-labeling approach to
      unambiguous NMR spectral assignments in nucleic acids.
AB  - We demonstrate that base and sugar protons within a DNA oligomer can be assigned
      unambiguously following site-specific 15N,13C isotope incorporation at levels as
      low as 1% enrichment. This simple and cost-effective methodology is demonstrated
      on the d(GGGTTCAGG) DNA sequence, which forms a dimeric G-quadruplex containing
      G.G.G.G tetrads sandwiched between G.(C-A) triads.

PMID- 11841272
TI  - A highly active Suzuki catalyst for the synthesis of sterically hindered biaryls:
      novel ligand coordination.
AB  - A catalyst system for the preparation of biaryls containing four ortho
      substituents via Suzuki coupling is described. The combination of a catalytic
      quantity of Pd2(dba)3 with either an electron-rich biarylphosphine or DPEPhos is
      effective using a wide range of substrates. The X-ray crystal structure of
      (dba)Pd(2-(9-phenanthryl)phenyl-dicyclohexylphosphine), in which the Pd is
      coordinated to the 9,10-double bond of the phenanthryl group, is also reported.

PMID- 11841273
TI  - Rhodium-catalyzed, regiospecific functionalization of polyolefins in the melt.
AB  - The rhodium-catalyzed, terminal-selective borylation of alkanes has been used to
      modify polyolefins. The functionalization of two materials, polyethylethylene
      (PEE) of molecular weights 1200 and 37 000, was conducted by combining bis
      pinacoldiboron and 2.5 mol % [Cp*RhCl2]2 in neat polymer and heating at 150
      degrees C. This procedure causes the polymer and boron reagent to melt, the
      catalyst to dissolve, and the reaction to form material with boryl groups at the
      terminal position of the polymer side chains. Oxidation of the borylated material
      generated polymers with hydroxyl groups at the terminal position of the side
      chains. The functionalization was conducted at various ratios of boron reagent to
      monomer. The resulting borylated and subsequent hydoxylated materials were
      characterized by 1H and 13C NMR spectroscopy, as well as MALDI-MS and GPC. Little
      change in polymer molecular weight and polydispersity was observed, and these
      data indicate that scission of the main chain does not occur. Measurements of the
      Tg of the polymers showed in increase in Tg of up to 50 degrees C after the
      modification. Thus, homogeneous, catalytic, selective alkane functionalization
      can be used to modify polymer properties.

PMID- 11841274
TI  - A new pathway for hydroamination. Mechanism of palladium-catalyzed addition of
      anilines to vinylarenes.
AB  - The mechanism of the hydroamination of vinylarenes with anilines catalyzed by
      phosphine-ligated palladium triflates was uncovered. eta3-Arylethyl diphosphine
      palladium triflate complexes, which result from migratory insertion of vinylarene
      into a palladium hydride triflate, were shown to be the resting state of the
      catalytic cycle. A series of these complexes has been isolated and fully
      characterized. The [(R)-Tol-BINAP][1-(2-naphthyl)ethyl]palladium triflate
      derivative 1a was crystallographically characterized. This complex reacted with
      aniline to form the N-phenethylaniline product in 83% yield. Reaction of the
      benzylic derivative [(R)-Tol-BINAP](eta3-benzyl)palladium triflate with aniline
      also formed the N-benzylaniline product in a high 87% yield. Predominant
      inversion of configuration from the reaction between 1a, which is enantiopure,
      and aniline showed that external attack of the amine on the eta3-arylethyl ligand
      occurred to form the product. This product from reaction of aniline with 1a is
      the opposite enantiomer to that obtained from the catalytic process. Thus, a
      minor diastereomer gives the major enantiomer in the catalytic cycle, and the
      major diastereomer gives the minor enantiomer. Consistent with this assertion,
      kinetic studies showed that the major diastereomer formed product with a rate
      constant roughly 3.5 times slower than the rate constant for the catalytic
      process that contains all diastereomers.

PMID- 11841275
TI  - A concise synthesis of the fully functional lactide core of cycloviracin B with
      implications for the structural assignment of related glycolipids.
AB  - The absolute stereochemistry at the site of attachment of the fatty acid residues
      to the lactide core of the glycolipids cycloviracin B1 (1) and glucolipsin A (13)
      has been elucidated as (3R,3'R) by comparison of their 13C NMR data with those of
      the three possible, differently configured core structures 9, 12, and 14.
      Moreover, a careful analysis of this set of NMR data allows us to conclude that
      the structures previously proposed for a seemingly closely related class of
      antivirally active compounds, i.e., the fattiviracin family, need revision. The
      key step en route to the symmetrical dilactones 9 and 12 consists of a highly
      efficient cyclodimerization process which exploits the template effect exerted by
      potassium cations on the hydroxy acid cyclization precursor. The latter is
      obtained in excellent overall yield by a sequence involving ring-opening Claisen
      condensation of pentadecanolide to form the functionalized beta-ketoester 4,
      asymmetric hydrogenation catalyzed by [(BINAP)RuCl2]2.NEt3, and a beta-selective
      glycosylation reaction using trichloroacetimidate 6. The unsymmetrical dilactone
      14, in contrast, is prepared by a stepwise approach based on a Yamaguchi
      lactonization as the means to close the macrocyclic ring.

PMID- 11841276
TI  - Toward inorganic electrides.
AB  - Electrides are materials in which alkali metals (Li through Cs) ionize to form
      bound alkali cations and "excess" electrons. The electrons reside in large
      cavities or channels or both in the host lattice. We report here the first
      synthesis of thermally stable inorganic electrides with cation-to-electron ratios
      of 1:1 as in organic electrides. Although alkali metal adducts to alumino
      silicate zeolites are well known, the cation-to-electron ratio is generally 3:1
      or greater because these zeolites contain alkali cations prior to incorporation
      of the alkali metal. In this work, two pure silica zeolites, ITQ-4and ITQ-7, with
      pore diameters of approximately 7 A, absorb up to 40 wt % cesium from the vapor
      phase (even at room temperature). The other alkali metals (except Li) can also be
      introduced at elevated temperatures. The optical and magnetic properties of the
      cesium-loaded samples suggest ionization to form Cs+ and e- with substantial
      electron-spin pairing. The metal-loaded samples are stable to at least 100
      degrees C and are able to reduce small aromatic molecules such as benzene and
      naphthalene to the radical anions within the pores of the zeolite.

PMID- 11841277
TI  - Enantioselective organocatalytic indole alkylations. Design of a new and highly
      effective chiral amine for iminium catalysis.
AB  - The indole framework has become widely identified as a "privileged" structure
      with representation in over 3000 natural isolates and 40 medicinal agents of
      diverse therapeutic action. A new strategy for asymmetric access to this
      important pharmacaphore has been accomplished that involves the amine catalyzed
      alkylation of indoles with alpha,beta-unsaturated aldehydes. Central to these
      studies has been the design of a new chiral amine catalyst that exhibits improved
      reactivity and selectivity for iminium catalysis. This new (2S,5S)-5-benzyl-2
      tert-butyl-imidazolidinone catalyst has enabled the conjugate addition of a
      variety of indole systems to a diverse range of alpha,beta-unsaturated aldehydes
      in high yield and with excellent levels of enantiocontrol (70-97% yield, 84-97%
      ee). A demonstration of the utility of this new organocatalytic alkylation for
      the rapid construction of biomedically relevant molecules is presented in the
      enantioselective synthesis of an indolobutyric acid COX-2 inhibitor.

PMID- 11841278
TI  - Synthesis of beta-lactones: a highly active and selective catalyst for epoxide
      carbonylation.
AB  - A new highly active and selective catalyst for the synthesis of beta-lactones
      from CO and epoxides is reported. The catalyst, [(N,N'-bis(3,5-di-tert
      butylsalicylidene) phenylenediamino)Al(THF)2][Co(CO)4]
      ([(salph)Al(THF)2][Co(CO)4]) is easily prepared from the corresponding
      (salph)AlCl and NaCo(CO)4. At 50 degrees C and 880 psi of CO, the catalyst (1 mol
      %) carbonylates epoxides such as propylene oxide, 1-butene oxide,
      epichlorohydrin, and isobutylene oxide to the lactones beta-butyrolactone, beta
      valerolactone, gamma-chloro-beta-butyrolactone, and beta-methyl-beta
      butyrolactone in high yield. (R)-Propylene oxide was carbonylated to (R)-beta
      butyrolactone with retention of stereochemistry.

PMID- 11841279
TI  - Catalytic regioselective introduction of allyl alcohol into the nonpolar
      polyolefins: development of one-pot synthesis of hydroxyl-capped polyolefins
      mediated by a new metallocene IF catalyst.
AB  - A new catalytic regioselective one-pot synthesis of hydroxyl-capped polyolefins
      is reported. This synthesis employs a new stereorigid bridged metallocene having
      an indenyl and a fluorenyl ligand named IF catalyst 1, exhibiting high catalytic
      performances. Here, we report on (1) the first example of allyl alcohol
      incorporation into the nonpolar polymer backbone using IF catalyst 1 and
      methylaluminoxane with high activity, high molecular weight, and high polar
      monomer uptake at high temperature, and (2) the first example of predominant end
      site-selective introduction of an alcohol group into the polyolefins. Moreover,
      we observed the mixed regioselectivity by the type of alkylaluminum.

PMID- 11841280
TI  - Fluorescent signaling based on control of excited state dynamics. Biarylacetylene
      fluorescent chemosensors.
AB  - We have previously reported that metal ion binding could restrict the excited
      state rotation of a biaryl chromophore, suppressing intersystem crossing and
      leading to increased emission. We have now applied the restriction of excited
      state dynamics to suppression of the other fundamental nonradiative decay
      pathway, internal conversion, in biarylacetylenes. This indicates that both
      nonradiative decay pathways are subject to conformational control, and that this
      signaling pathway should be generally accessible in simple flexible fluorophores.

PMID- 11841281
TI  - Direct assignment of the absolute configuration of a distinct class of
      deoxyribonucleoside cyclic N-acylphosphoramidites at phosphorus by M-GOESY
      nuclear magnetic resonance spectroscopy.
AB  - The determination of the absolute configuration of deoxyribonucleoside cyclic N
      acylphosphoramidites at phosphorus toward the synthesis of P-stereodifined
      phosphorothioated oligodeoxyribonucleotides is easily accomplished with computer
      assisted molecular modeling and M-GOESY NMR spectroscopy. Specifically, computer
      modeling diasteromeric phosphoramidite 3 has identifed a proximal (2.55 A)
      through-space interaction between benzylic H-5 and sugar H-2' ', which can
      predictably be detected by M-GOESY NMR in SP-3 but not in RP-3 because of being
      too distant (5.85 A). Consistent with computer-assisted modeling predictions, M
      GOESY NMR spectra of SP-3 and RP-3 revealed NOE signals generated from nuclei
      near the selectively excited H-2' ' that are common to both SP-3 and RP-3, namely
      those of H-2', H-4', H-3', and H-1'. In addition, a diagnostic NOE signal at 5.5
      ppm (benzylic H-5) is, as predicted, only detected in SP-3 and thus provides an
      unequivocal assessment of the configuration of the diastereomer at phosphorus. M
      GOESY NMR data also confirm that the condensation of deoxyribonucleoside cyclic N
      acylphosphoramidites with base-activated nucleosidic or nucleotidic 5'-hydroxyls
      proceeds via a single nucleophilic event.

PMID- 11841282
TI  - Light-harvesting heptadecameric porphyrin assemblies.
AB  - New porphyrin assemblies containing 17 porphyrin molecules are constructed by
      using free base TPP-type porphyrins having eight pyrazine moieties 1.
      Spectroscopic titration of dimeric [meso-tetrakis(2-carboxy-4
      nonylphenyl)porphyrinato]zinc(II) 2 with these porphyrins shows that the
      processes of the formation of the heptadecameric porphyrin assemblies may be
      analyzed as eight independent equilibrium processes with an identical binding
      constant. All binding constants are larger than 5 x 107 M-1 which is the
      determinable upper limit of the present titration method. In all cases, the
      fluorescence spectrum of the 1:8 mixture of 1 and 2 consists of the major
      fluorescence of 1 and the minor one of 2.pyrazine complex even in the presence of
      the large excess of the antenna pigments. The observed spectra are well
      reconstructed by the form of faF1 + fbF2, where F1 and F2 are the fluorescence of
      1 and the 2.pyrazine complex measured separately at the corresponding
      concentrations. Interestingly, the general trend that values of fa are nearly
      equal to those of r564 x (1 - fb) in all cases is found, where r564 is the
      absorption ratios of the 2.pyrazine moiety and the central free base porphyrin in
      the assemblies at 564 nm. The observation indicates the excitation of the central
      porphyrin is directly enhanced by the absorption of the antenna pigments even in
      such large scale assemblies. Thus, the antenna effect for 1 having largest r564
      results in 77 times fluorescence enhancement of the central free base porphyrin.
      The systems also show interesting dependency of energy-transfer efficiencies on
      the topological arrangement of the antenna elements.

PMID- 11841284
TI  - Synthesis of single-crystalline perovskite nanorods composed of barium titanate
      and strontium titanate.
AB  - We report the solution-based synthesis of single-crystalline nanorods composed of
      barium titanate (BaTiO3) and strontium titanate (SrTiO3), which yields well
      isolated nanorods with diameters ranging from 5 to 60 nm and lengths reaching up
      to >10 mum. Electron microscopy and diffraction measurements show that these
      nanorods are composed of single-crystalline cubic perovskite BaTiO3 and SrTiO3
      with a principal axis of the unit cell preferentially aligned along the wire
      length. These BaTiO3 and SrTiO3 nanorods should provide promising materials for
      fundamental investigations on nanoscale ferroelectricity, piezoelectricity, and
      paraelectricity.

PMID- 11841283
TI  - Recognition of polarized lipid bilayers by p-oligophenyl ion channels: from push
      pull rods to push-pull barrels.
AB  - Design, synthesis, and evaluation of 14-methoxy-84-methylsulfonyl
      22,33,42,53,62,73-hexa(Gla-Leu-Lys-Leu-NH2)-p-octiphenyl (1) and 14,84-bismethoxy
      22,33,42,53,62,73-hexa(Gla-Leu-Lys-Leu-NH2)-p-octiphenyl (2) are described (Gla =
      -OCH2CO-). Nanomolar concentrations of push-pull rod 1 are found to suffice to
      selectively form ion channels in polarized spherical bilayer membranes composed
      of egg yolk phosphatidylcholine. Exponential dependence of the ion-channel
      activity on membrane polarization reveals a gating charge of 0.85/channel.
      Independence of the activity of push-push rod 2 on membrane potential
      demonstrates that cell membrane recognition originates from the axial dipole in
      push-pull rod 1. Nonlinear concentration dependence of activity at -180 mV
      indicates parallel self-assembly of push-pull rod 1 into a tetrameric barrel
      stave supramolecule.

PMID- 11841285
TI  - Reversible control of enzymatic transglycosylations in supercritical fluoroform
      using a lipid-coated beta-D-galactosidase.
AB  - The transgalactosylation rate catalyzed by the lipid-coated beta-d-galactosidase
      in supercritical fluoroform (scCHF3) can be reversibly controlled by changing
      temperature or pressure (reflecting polarity changes) without damaging enzymes.

PMID- 11841286
TI  - Trans-hydrogen-bond (h2)J(NN) and (h1)J(NH) couplings in the DNA A-T base pair:
      natural bond orbital analysis.
AB  - Natural bond orbital (NBO) analysis described here demonstrates that trans
      hydrogen-bond (trans-H-bond) NMR J couplings in the DNA A-T base pair, h2JNN and
      h1JNH, are determined largely by three terms: two Lewis-type contributions (the
      single-orbital contribution from the adenine lone pair and the contribution from
      the sigmaN3H3 natural bond orbital of the thymine ring) and one contribution from
      pairwise delocalization of spin density (between the lone pair in adenine and the
      sigma* antibonding orbital linking N3 and H3 of thymine). For h2JNN coupling, all
      three contributions are positive, whereas for h1JNH coupling, the delocalization
      term is negative, and the other two terms are positive, resulting in a small net
      positive coupling constant. This result rationalizes the experimental findings
      that the two-bond coupling (h2JNN approximately 9 Hz) is larger than the one-bond
      coupling (h1JNH approximately 3 Hz) and demonstrates that the same
      hyperconjugative and steric mechanisms that stabilize the H-bond are involved in
      the transmission of J coupling information. The N1...H3-N3 H-bond of the DNA A-T
      base pair is found to exhibit significant covalent character, but steric effects
      contribute almost equally to the trans-H-bond coupling.

PMID- 11841287
TI  - The molecular mechanism of stabilization of proteins by TMAO and its ability to
      counteract the effects of urea.
AB  - Trimethylamine n-oxide (TMAO) is a naturally occurring osmolyte that stabilizes
      proteins and offsets the destabilizing effects of urea. To investigate the
      molecular mechanism of these effects, we have studied the thermodynamics of
      interaction between TMAO and protein functional groups. The solubilities of a
      homologous series of cyclic dipeptides were measured by differential refractive
      index and the dissolution heats were determined calorimetrically as a function of
      TMAO concentration at 25 degrees C. The transfer free energy of the amide unit (
      CONH-) from water to 1 M TMAO is large and positive, indicating an unfavorable
      interaction between the TMAO solution and the amide unit. This unfavorable
      interaction is enthalpic in origin. The interaction between TMAO and apolar
      groups is slightly favorable. The transfer free energy of apolar groups from
      water to TMAO consists of favorable enthalpic and unfavorable entropic
      contributions. This is in contrast to the contributions for the interaction
      between urea and apolar groups. Molecular dynamics simulations were performed to
      provide a structural framework for the interpretation of these results. The
      simulations show enhancement of water structure by TMAO in the form of a slight
      increase in the number of hydrogen bonds per water molecule, stronger water
      hydrogen bonds, and long-range spatial ordering of the solvent. These findings
      suggest that TMAO stabilizes proteins via enhancement of water structure, such
      that interactions with the amide unit are discouraged.

PMID- 11841288
TI  - Probing the structural determinants of type II' beta-turn formation in peptides
      and proteins.
AB  - The structural determinants of type II' beta-turns were probed through a
      comprehensive CD, NMR, and molecular dynamics analysis of 10 specially designed
      beta-hairpin peptides. The peptide model used in this study is a synthetic, water
      soluble, 14-residue cyclic analogue of gramicidin S which contains two well
      defined type II' beta-turns connected by a highly stable, amphipathic,
      antiparallel beta-sheet. A variety of coded and noncoded amino acids were
      systematically substituted in one of the two type II' turns to analyze the
      effects of backbone chirality, side-chain steric restriction, and side-chain/side
      chain interactions. beta-Sheet content (as measured through a variety of
      experimental methods), molecular dynamics, and 3D structural analysis of the turn
      regions were used to assess the effects of each amino acid substitution on type
      II' beta-turn stabilization. Our results demonstrate that backbone
      heterochirality, which determines equatorial and axial side-chain orientation at
      the i+1 and i+2 residues of type II' turns, may account for up to 60% of type II'
      beta-turn stabilization. Steric restriction through side-chain N-alkylation
      appears to enhance type II' beta-turn propensity and may account for up to 20% of
      type II' beta-turn stabilization. Finally, aromatic/proline side-chain
      interactions appear to account for approximately 10% of type II' beta-turn
      stabilization. We believe this information could be particularly useful for the
      prediction of beta-turn propensity, the development of peptide-based drugs, and
      the de novo design of peptides, proteins, and peptidyl mimetics.

PMID- 11841289
TI  - The nature of the intermediates in the reactions of Fe(III)- and Mn(III)
      microperoxidase-8 with H(2)O(2): a rapid kinetics study.
AB  - Kinetic studies were performed with microperoxidase-8 (Fe(III)MP-8), the
      proteolytic breakdown product of horse heart cytochrome c containing an
      octapeptide linked to an iron protoporphyrin IX. Mn(III) was substituted for
      Fe(III) in Mn(III)MP-8. The mechanism of formation of the reactive metal-oxo and
      metal-hydroperoxo intermediates of M(III)MP-8 upon reaction of H(2)O(2) with
      Fe(III)MP-8 and Mn(III)MP-8 was investigated by rapid-scan stopped-flow
      spectroscopy and transient EPR. Two steps (k(obs1) and k(obs2)) were observed and
      analyzed for the reaction of hydrogen peroxide with both catalysts. The plots of
      k(obs1) as function of [H(2)O(2)] at pH 8.0 and pH 9.1 for Fe(III)MP-8, and at pH
      10.2 and pH 10.9 for Mn(III)MP-8, exhibit saturation kinetics, which reveal the
      accumulation of an intermediate. Double reciprocal plots of 1/k(obs1) as function
      of 1/[H(2)O(2)] at different pH values reveal a competitive effect of protons in
      the oxidation of M(III)MP-8. This effect of protons is confirmed by the linear
      dependence of 1/k(obs1) on [H(+)] showing that k(obs1) increases with the pH. The
      UV-visible spectra of the intermediates formed at the end of the first step
      (k(obs1)) exhibit a spectrum characteristic of a high-valent metal-oxo
      intermediate for both catalysts. Transient EPR of Mn(III)MP-8 incubated with an
      excess of H(2)O(2), at pH 11.5, shows the detection of a free radical signal at g
      approximately equal to 2 and of a resonance at g approximately equal to 4
      characteristic of a Mn(IV) (S = 3/2) species. On the basis of these results, the
      following mechanism is proposed: (i) M(III)MP-8-OH(2) is deprotonated to M(III)MP
      8-OH in a rapid preequilibrium step, with a pK(a) = 9.2 +/- 0.9 for Fe(III)MP-8
      and a pK(a) = 11.2 +/- 0.3 for Mn(III)MP-8; (ii) M(III)MP-8-OH reacts with
      H(2)O(2) to form Compound 0, M(III)MP8-OOH, with a second-order rate constant
      k(1) = (1.3 +/- 0.6) x 10(6) M(-1) x s(-1) for Fe(III)MP-8 and k(1) = (1.6 +/-
      0.9) x 10(5) M(-1) x s(-1) for Mn(III)MP-8; (iii) this metal-hydroperoxo
      intermediate is subsequently converted to a high-valent metal-oxo species,
      M(IV)MP-8=O, with a free radical on the peptide (R(*+)). The first-order rate
      constants for the cleavage of the hydroperoxo group are k(2) = 165 +/- 8 s(-1)
      for Fe(III)MP-8 and k(2) = 145 +/- 7 s(-1) for Mn(III)MP-8; and (iv) the proposed
      M(IV)MP-8=O(R(*+)) intermediate slowly decays (k(obs2)) with a rate constant of
      k(obs2) = 13.1 +/- 1.1 s(-)(1) for Fe(III)MP-8 and k(obs2) = 5.2 +/- 1.2 s(-1)
      for Mn(III)MP-8. The results show that Compound 0 is formed prior to what is
      analyzed as a high-valent metal-oxo peptide radical intermediate.

PMID- 11841290
TI  - Stability and selectivity of unnatural DNA with five-membered-ring nucleobase
      analogues.
AB  - In an effort to develop an orthogonal third base pair for the storage of genetic
      information, thiophene and furan heterocycles have been examined as nucleobase
      analogues. The stability of the unnatural bases was evaluated in duplex DNA
      paired opposite other unnatural bases as well as opposite the natural bases.
      Several unnatural base pairs are identified that are both reasonably stable and
      strongly selective against mispairing with native bases. These results expand the
      potential nucleobase analogues with which the genetic alphabet may be expanded to
      include five-membered-ring heterocycles.

PMID- 11841291
TI  - Phosphonate lipid tubules II.
AB  - We describe a new chiral tubule-forming lipid in which the C-O-P phosphoryl
      linkage of the archetypal tubule-forming molecule, 1,2-bis(10,12-tricosadiynoyl)
      sn-glycero-3-phosphocholine, "DC(8,9)PC", is replaced by a C-P linkage. Tubule
      formation with this phosphonate analogue proceeds under the same mild conditions
      as with DC(8,9)PC and produces similar yields, but synchrotron small-angle X-ray
      scattering, atomic force microscopy, and optical microscopy show the new tubules
      to have diameters 1.94 times as great, to be significantly shorter, and to be
      thinner-walled. A significant portion of the enantiomerically pure chiral
      phosphonate precipitate is in the form of stable open helices, and these helices
      are divided almost evenly between left- and right-handed members.

PMID- 11841293
TI  - TreeDock: a tool for protein docking based on minimizing van der Waals energies.
AB  - Predicting protein-protein and protein-ligand docking remains one of the
      challenging topics of structural biology. The main problems are (i) to reliably
      estimate the binding free energies of docked states, (ii) to enumerate possible
      docking orientations at a high resolution, and (iii) to consider mobility of the
      docking surfaces and structural rearrangements upon interaction. Here we present
      a novel algorithm, TreeDock, that addresses the enumeration problem in a rigid
      body docking search. By representing molecules as multidimensional binary search
      trees and by exploring a sufficient number of docking orientations such that two
      chosen atoms, one from each molecule, are always in contact, TreeDock is able to
      explore all clash-free orientations at very fine resolution in a reasonable
      amount of time. Due to the speed of the program, many contact pairs can be
      examined to search partial or complete surface areas. The deterministic
      systematic search of TreeDock is in contrast to most other docking programs that
      use stochastic searches such as Monte Carlo or simulated annealing methods. At
      this point, we have used the Lennard-Jones potential as the only scoring function
      and show that this can predict the correct docked conformation for a number of
      protein-protein and protein-ligand complexes. The program is most powerful if
      some information is known about the location of binding faces from NMR chemical
      shift perturbation studies, orientation information from residual dipolar
      coupling, or mutational screening. The approach has the potential to include
      docking-site mobility by performing molecular dynamics or other randomization
      methods of the docking site and docking families to families of structures. The
      performance of the algorithm is demonstrated by docking three complexes of
      immunoglobulin superfamily domains, CD2 to CD58, the V(alpha) domain of a T-cell
      receptor to its V(beta) domain, and a T-cell receptor to a pMHC complex as well
      as a small molecule inhibitor to a phosphatase.

PMID- 11841292
TI  - A novel approach for characterizing protein ligand complexes: molecular basis for
      specificity of small-molecule Bcl-2 inhibitors.
AB  - The increasing diversity of small molecule libraries has been an important source
      for the development of new drugs and, more recently, for unraveling the
      mechanisms of cellular events-a process termed chemical genetics.(1)
      Unfortunately, the majority of currently available compounds are mechanism-based
      enzyme inhibitors, whereas most of cellular activity regulation proceeds on the
      level of protein-protein interactions. Hence, the development of small molecule
      inhibitors of protein-protein interactions is important. When screening compound
      libraries, low-micromolar inhibitors of protein interactions can be routinely
      found. The enhancement of affinities and rationalization of the binding mechanism
      require structural information about the protein-ligand complexes.
      Crystallization of low-affinity complexes is difficult, and their NMR analysis
      suffers from exchange broadening, which limits the number of obtainable
      intermolecular constraints. Here we present a novel method of ligand validation
      and optimization, which is based on the combination of structural and
      computational approaches. We successfully used this method to analyze the basis
      for structure-activity relationships of previously selected (2) small molecule
      inhibitors of the antiapoptotic protein Bcl-xL and identified new members of this
      inhibitor family.

PMID- 11841294
TI  - First systematic band-filling control in organic conductors.
AB  - The systematic study of band-filling control for four kinds of organic conductors
      with various kinds of ground states has succeeded. (1) By partial substitution of
      (GaCl(4))(-) by (MCl(4))(2-) [M = Co, Zn] in the anion blocking layer of lambda
      ET(2)(GaCl(4))(-) [ET = bis(ethylenedithio)tetrathiafulvalene], single crystals
      of lambda-ET(2)(GaCl(4))(-)(1-x)(MCl(4))(2-)(x) [x = 0.0, 0.05, 0.06] have been
      obtained. The resistivity at room temperature decreases from 3 Omega cm (x = 0.0)
      to 0.1 Omega cm (x = 0.06) by doping to the antiferromagnet with an effective
      half-filled band (x = 0.0). (2) Another 2:1 (donor/anion) salt, delta'
      ET(2)(GaCl(4))(-), which is a spin gap material, has been doped as delta'
      ET(2)(GaCl(4))(-)(1-x)(MCl(4))(2-)(x) [x = 0.05, 0.14]. The resistivity is
      lowered from 10 Omega cm (x = 0.0) to 0.3 Omega cm (x = 0.14). For both 2:1
      salts, the semiconducting behaviors have transferred to relatively conductive
      semiconducting ones by doping. (3) As for alpha-type 3:1 salts, the parent
      material is in a charge-ordering state such as alpha-(ET(+)ET(+)ET(0))(CoCl(4))(2
      )(TCE), where the charge-ordered donors are dispersed in the two-dimensional
      conducting layer. Although the calculation of alpha-ET(3)(CoCl(4))(2-)(TCE) shows
      a band-insulating nature, and the crystal structure analysis indicates that this
      material is in a charge-ordering state, the metallic behavior down to 165 K has
      been observed. With doping of (GaCl(4))(-) to the alpha-system, isostructural
      alpha-ET(3)(CoCl(4))(2-)(1-x)(GaCl(4))(-)(x)(TCE) [x = 0.54, 0.57, 0.62] have
      been afforded, where the pattern of the horizontal stripe-type charge ordering
      changes with an increase of x. (4) By doping (GaCl(4))(-) to the 3:2 gapless band
      insulator which is isostructural to beta'-ET(3)(MCl(4))(2)(2-) [M = Zn, Mn], the
      obtained beta'-ET(3)(CoCl(4))(2-)(2-x)(GaCl(4))(-)(x) [x = 0.66, 0.88] shows
      metallic behavior down to 100 and 140 K, respectively. They are the first
      metallic states in organic conductors by band-filling control of the gapless band
      insulator. These systematic studies of band-filling control suggest that the
      doping to the gapless band insulator with a pseudo-1/2-filled band is most
      effective.

PMID- 11841295
TI  - An improved catalyst for the asymmetric arylation of ketone enolates.
AB  - A new catalyst system for the enantioselective alpha-arylation of ketones is
      reported. This catalyst, prepared from Pd(2)(dba)(3) and a bulky dialkylphosphino
      binaphthyl ligand, is able to effect the asymmetric arylation of ketone enolates
      with aryl bromides utilizing NaO(t)()Bu as base. These new catalysts enjoy much
      higher reactivity than previous systems; arylation reactions could be effected at
      room temperature with only 2 mol % of the Pd catalyst. The coupling of alpha
      alkyl-alpha'-protected cyclopentanones proceeded in high yield, and the resulting
      quaternary stereogenic center was installed in up to 94% ee.

PMID- 11841296
TI  - Supramolecular organization of alpha,alpha'-disubstituted sexithiophenes.
AB  - The self-assembly of alpha,alpha'-linked sexithiophenes with chiral and achiral
      penta(ethylene glycol) chains attached at the alpha-positions of the terminal
      rings, that is, 2,2':5',2'':5'',2''':5''',2'''':5'''',2'''''-sexithiophene
      5,5'''''-dicarboxylic acid-2S)-2-methyl-3,6,9,12,15-pentaoxahexadecyl ester (1)
      and 2,2':5',2'':5'',2''':5'''',2''''':5''''',2'''''-sexithiophene-5,5'''''
      dicarboxylic acid-3,6,9,12,15-pentaoxahexadecyl ester (2), respectively is
      described. Analysis of the UV/vis, fluorescence, circular dichroism, and circular
      polarization of luminescence spectroscopic data shows that these compounds form
      chiral aggregates in polar solvents and in the solid state. In n-butanol
      aggregation occurs at temperatures below 30 degrees C, while above this threshold
      temperature the aggregates break up without an intermediate disordered state of
      aggregation, and the compounds are molecularly dissolved. The "melting
      temperature" of the aggregates depends on the concentration of sexithiophene,
      indicating that the optical changes observed are a result of intermolecular
      processes. Mass spectrometric measurements reveal that 1 and 2 can form mixed
      aggregates. Analysis of the optical spectra reveals that in these mixed
      aggregates, chiral 1 molecules act as "sergeants" to direct the packing of the
      "soldiers" 2, illustrating cooperativity within the columns. In water, the same
      type of chiral aggregates are formed as in n-butanol below 30 degrees C; however,
      these aggregates are still present, but the chirality is lost above 30 degrees C.
      In spin-coated films of 1 chiral aggregates are present. AFM studies show that 1
      self-organizes into chiral fiberlike structures in the solid state. Furthermore
      both 1 and 2 display thermotropic liquid crystalline behavior between 180 and 200
      degrees C.

PMID- 11841298
TI  - Controlling chemoselectivity in vinyl and allylic C-X bond activation with
      palladium catalysis: a pK(a)-based electronic switch.
AB  - It has been demonstrated that the same Pd catalyst can be used to effect allylic
      substitution or vinylic cross-coupling reactions selectively and interchangeably
      on polyfunctionalized olefin building blocks despite the differences in reaction
      mechanism. This was achieved by altering the pK(a) of the conjugate acid of the
      allylic leaving group while keeping the vinyl coupling partner constant. In the
      case of 2,3-dibromo-1-propene, Pd-catalyzed allylic ionization with malonate
      nucleophile proceeded selectively and quantitatively in the presence of the
      Suzuki reaction components necessary for cross-coupling. Conversely, the bromide
      of 2-bromo-1-(4-ethylphenoxy)-2-propene could be cross-coupled selectively
      without activation of the allylic phenoxy substituent. In both reactions, the
      same catalyst could then be used to complete the sequence, which typically
      involved heating as the trigger to promote the second, more reluctant reaction.
      Mechanistic considerations as well as synthetic applications demonstrating the
      value of this interchangeable catalyzed sequence are presented.

PMID- 11841297
TI  - Ring scission of diastereomeric 4-butylspiropentylcarbinyl radicals as a chemical
      model for identifying enzyme-catalyzed FAD adducts resulting from
      spiropentylacetyl-CoA.
AB  - Both diastereomeric 4-butylspiropentylcarbinyl bromides (14a and 14b) were
      synthesized in seven steps starting from 1-heptyne, and the stereochemical
      assignments based upon NOE experiments were confirmed by converting their
      immediate alcohol precursors (13a and 13b) to 1,4-dibutylspiropentanes (17a and
      17b) with C(1) and C(2) symmetry. Each bromide was used to generate its
      corresponding spiropentylcarbinyl radical (18a and 18b) via its AIBN-initiated
      tri-n-butyltin hydride reduction. The radical-trapped products are identified,
      the preferred ring scission mode is identified (C1[bond] C2 bond cleavage), and
      the estimated rates for the ring opening of 4-butylspiropentylcarbinyl radical
      (18, k(25) degrees C > or = approximately 5 x 10(9) s(-1)) and 2-butyl-1
      vinylcyclopropylcarbinyl radical (33, k(25) degrees C approximately 5 x 10(8) s(
      1)) are reported. High-level ab initio calculations addressing the ring-opening
      isomerizations of cyclopropylcarbinyl and spiropentylcarbinyl radicals also are
      presented. These results in conjunction with a previous study enable us to
      propose two structures for the enzyme-catalyzed FAD adducts resulting from
      spiropentylacetic acid-CoA, a synthetic byproduct of fatty acid metabolism.

PMID- 11841299
TI  - Mechanistic studies on the B(C(6)F(5))(3) catalyzed allylstannation of aromatic
      aldehydes with ortho donor substituents.
AB  - Mechanistic studies on the B(C(6)F(5))(3) catalyzed allylstannation of isomeric
      substituted benzaldehydes are reported. Confirming a report by Maruoka et al.,
      good (5:1) to excellent (>20:1) selectivities for ortho over para isomers are
      observed when 1:1 mixtures (X = OMe, Cl, F, OTBS) are allylstannated with
      C(3)H(5)SnBu(3) in the presence of B(C(6)F(5))(3) (2.5% per CHO). The best
      selectivities are observed for the anisaldehydes. Multinuclear NMR studies on
      solutions of B(C(6)F(5))(3) and C(3)H(5)SnBu(3) (1:1 to 1:5) show that the borane
      abstracts the allyl group from the organotin reagent, forming an adduct
      (C(6)F(5))(3)B...CH(2)CHCH(2)SnBu(3), 1, or ion pair
      [(C(6)F(5))(3)BCH(2)CH=CH(2)](-)[Bu(3)SnCH(2)CHCH(2)SnBu(3)](+), 2, depending on
      the reagent ratio. These compounds are important in the mechanism of Lewis acid
      catalyzed 1,3-isomerization of substituted allyl stannanes. When allyltin reagent
      is added to solutions of B(C(6)F(5))(3) and ortho-anisaldehyde (1:5) at -60
      degrees C, conversion to the stannylium ion pair [Bu(3)Sn(ortho
      anisaldehyde)(2)](+)[o-ArCH(allyl)OB(C(6)F(5))(3)](-), o,o-4, is observed. The
      structure of this species was confirmed by (1)H, (11)B, (19)F, and (119)Sn NMR
      spectroscopy and by forming related ion pairs (o-5 and o,o-5) utilizing the
      [B(C(6)F(5))(4)](-) counteranion via reaction of [Bu(3)Sn](+)[B(C(6)F(5))(4)](-)
      with aldehyde. The anion in o,o-4 is formed via direct allylation of the ortho
      anisaldehyde/B(C(6)F(5))(3) adduct o-3, while the cation arises upon aldehyde
      ligation of the resulting tributylstannylium ion. The crystal structure of the
      related derivative ortho-C(6)H(4)(OMe)CHO x SnMe(3)BF(4), 6, showed that the
      aldehyde binds the tin nucleus only through the carbonyl oxygen. Similar
      reactions using para-anisaldehyde show that formation of p,p-4 occurs at a much
      slower rate, again demonstrating the preference for the ortho substituted
      substrates. For similar experiments using benzophenone, however, formation of the
      ion pair [Bu(3)Sn(Ph(2)CO)(2)](+)[(C(3)H(5))B(C(6)F(5))(3)](-), 8, was observed,
      illustrating the differences subtle changes in substrate can bring. Ion pair 8 is
      formed via the trapping of 1 by the benzophenone substrate. In the presence of
      excess aldehyde and allyltin reagent, ion pair o,o-4 catalyzes the
      allylstannation of aldehyde to give the product stannyl ether. Several lines of
      experimental evidence suggest this is the true catalyst in the system. The
      chemoselectivity observed thus does not rely on classical chelation control in
      any way. Rather, we propose that the ortho donor group stabilizes the developing
      positive charge at the beta carbon of the allyl group and the tin atom during the
      allylation event. This stabilization renders the ortho substituted substrates
      kinetically favored toward allylation irrespective of the Lewis acid employed.

PMID- 11841301
TI  - Stereochemistry of lactide polymerization with chiral catalysts: new
      opportunities for stereocontrol using polymer exchange mechanisms.
AB  - The synthesis of chiral aluminum and yttrium alkoxides and their application for
      lactide polymerization are reported. The complexes (SalBinap)MOR [4, M = Al, R =
      (i)Pr; 5, M = Y, R = (CH(2))(2)NMe(2)] are synthesized by reacting the ligand
      (SalBinap)H(2) [2,2'-[(1,1'-binaphthalene)-2,2'
      diylbis(nitrilomethylidyne)]bisphenol] with the appropriate metal trisalkoxide.
      While enantiomerically pure yttrium complex 5 did not effect stereocontrol in the
      polymerization of either meso- or rac-lactide, homochiral 4 was found to exhibit
      excellent stereocontrol in a range of lactide polymerizations. Enantiomerically
      pure 4 polymerizes meso-lactide to syndiotactic poly(lactic acid) (PLA), while
      rac-4 polymerizes meso- and rac-lactide to heterotactic and isotactic stereoblock
      PLA, respectively. On the basis of the absolute stereochemistry of ring-opening
      of meso-lactide using (R)-4, a polymer exchange mechanism is proposed to account
      for the PLA microstructures resulting from rac-4.

PMID- 11841300
TI  - Highly selective hydrolytic kinetic resolution of terminal epoxides catalyzed by
      chiral (salen)Co(III) complexes. Practical synthesis of enantioenriched terminal
      epoxides and 1,2-diols.
AB  - The hydrolytic kinetic resolution (HKR) of terminal epoxides catalyzed by chiral
      (salen)Co(III) complex 1 x OAc affords both recovered unreacted epoxide and 1,2
      diol product in highly enantioenriched form. As such, the HKR provides general
      access to useful, highly enantioenriched chiral building blocks that are
      otherwise difficult to access, from inexpensive racemic materials. The reaction
      has several appealing features from a practical standpoint, including the use of
      H(2)O as a reactant and low loadings (0.2-2.0 mol %) of a recyclable,
      commercially available catalyst. In addition, the HKR displays extraordinary
      scope, as a wide assortment of sterically and electronically varied epoxides can
      be resolved to > or = 99% ee. The corresponding 1,2-diols were produced in good
      to-high enantiomeric excess using 0.45 equiv of H(2)O. Useful and general
      protocols are provided for the isolation of highly enantioenriched epoxides and
      diols, as well as for catalyst recovery and recycling. Selectivity factors
      (k(rel)) were determined for the HKR reactions by measuring the product ee at ca.
      20% conversion. In nearly all cases, k(rel) values for the HKR exceed 50, and in
      several cases are well in excess of 200.

PMID- 11841302
TI  - Synthesis and structural characterization of the first quaternary plutonium
      thiophosphates: K(3)Pu(PS(4))(2) and APuP(2)S(7) (A = K, Rb, Cs).
AB  - The first quaternary plutonium metal thiophosphates have been synthesized by the
      reactive flux method and characterized by single-crystal X-ray diffraction:
      K(3)Pu(PS(4))(2) (I), KPuP(2)S(7) (II), RbPuP(2)S(7) (III), and CsPuP(2)S(7)
      (IV). All four compounds crystallize in the monoclinic space group P2(1)/c with Z
      = 4. Compound I has cell parameters of a = 9.157(1) A, b = 16.866(2) A, c =
      9.538(1), and beta = 90.610(3)degrees. Compound II has cell parameters of a =
      9.641(1) A, b = 12.255(1) A, c = 9.015(1) A, and beta = 90.218(1)degrees.
      Compound III has cell parameters of a = 9.8011(6) A, b = 12.3977(7) A, c =
      9.0263(5) A, and beta = 90.564(1)degrees. Compound IV has cell parameters of a =
      10.1034(7) A, b = 12.5412(9) A, c = 9.0306(6) A, and beta = 91.007(1)degrees.
      Compound I is isostructural to a family of rare-earth metal thiophosphates and
      comprises bicapped trigonal prismatic PuS(8) polyhedra linked in chains through
      edge-sharing interactions and through thiophosphate tetrahedra. Compounds II-IV
      crystallize in a known structure type not related to any previously observed
      actinide thiophosphates and contain the (P(2)S(7))(4-) corner-shared
      bitetrahedral ligand as a structural building block. A summary of important bond
      distances and angles for these new plutonium thiophosphate materials is compared
      to the limited literature on plutonium solid-state compounds. Diffuse reflectance
      spectra confirm the Pu(III) oxidation state and Raman spectroscopy confirms the
      tetrahedral PS(4)(3-) building block in all structures.

PMID- 11841303
TI  - Calix[6]arene-based cuprous "funnel complexes": a mimic for the substrate access
      channel to metalloenzyme active sites.
AB  - Two calixarene-based model systems (a and b) for monocopper enzymes are compared.
      Both present a tris(pyridine) coordination site for Cu that mimics the imidazole
      rich neutral binding site in enzymes. Upon reaction with 1 equiv of copper(I),
      the tridentate ligands gave rise to ill-defined unsymmetrical complexes. However,
      in the presence of an organonitrile RCN (R = Me, Et, Ph), tetrahedral species
      were obtained, with the nitrilo ligand included in the calixarene hydrophobic
      cone. System b presents a larger cavity than system a, with a wider opening
      thanks to the removal of three tBu groups from the calixarene structure. As a
      result, the recognition pattern for MeCN vs PhCN is inverted, and the relative
      affinity constants differ by 3 orders of magnitude. The mechanism of the
      acetonitrile exchange at the cuprous centers was studied by (1)H NMR
      spectroscopy. Thermodynamic and kinetic data show that it follows a dissociative
      pathway in both cases. The main differences between systems a and b stem from the
      presence of a door that entraps the guest in case a. In system b indeed, the
      removal of three calixarene tBu groups led to a 100-fold acceleration of the MeCN
      exchange rate. Hence, these supramolecular systems provide a rare and interesting
      model for the hydrophobic substrate channel giving access to a metalloenzyme
      active site.

PMID- 11841304
TI  - Calix[4]tubes: a new class of potassium-selective ionophore.
AB  - A new class of cryptand-like ionophore based on a bis calix[4]arene structure has
      been developed. These molecules proved highly selective for complexation of
      potassium over all group I metal cations and barium. A range of symmetric and
      asymmetric calix[4]tubes featuring either alkyl or phenyl substituents at the
      upper rim have been synthesized in exceptional yield. Alteration of the
      calix[4]arene upper rim environment enables fine-tuning of the rate of potassium
      uptake, which can be evaluated through the conformational change on binding by
      NMR studies. Selectivity of potassium complexation has been demonstrated using
      NMR and electrospray mass spectral techniques. Molecular modeling studies,
      derived from crystallographic data, confirm that the potassium metal cation is
      complexed via the axial route, passing through the calix[4]arene annulus, and
      provide evidence for complexation rate and selectivity.

PMID- 11841305
TI  - Diversity-oriented synthesis of biaryl-containing medium rings using a one
      bead/one stock solution platform.
AB  - Diversity-oriented synthesis of structurally complex and diverse small molecules
      can be used as the first step in a process to explore cellular and organismal
      pathways. The success of this process is likely going to be dependent on advances
      in the synthesis of small molecules having natural product-like structures in an
      efficient and stereoselective manner. The development, scope, and mechanism of
      the oxidation of organocuprates was investigated and exploited in the
      atropdiastereoselective synthesis of biaryl-containing medium rings (9-, 10-, and
      11-membered rings). The methodology was performed on high-capacity, large
      polystyrene beads by metalating aryl bromides with i-PrBu(2)MgLi, followed by
      transmetalating with CuCN x 2LiBr and then oxidizing with 1,3-dinitrobenzene, and
      was used in a diversity-oriented synthesis of biaryl-containing medium rings
      (library total theoretical maximum 1412 members). The high capacity beads were
      arrayed into 384-well plates and, using a process optimized during the
      development of a one bead/one stock solution technology platform, converted into
      arrays of stock solutions, with each stock solution containing largely one
      compound. These stock solutions were used in numerous phenotypic and protein
      binding assays. The process described outlines a pathway that we feel will
      contribute to a comprehensive and systematic chemical approach to exploring
      biology (chemical genetics).

PMID- 11841306
TI  - A new class of functionalized terpyridyl ligands as building blocks for
      photosensitized supramolecular architectures. Synthesis, structural, and
      electronic characterizations.
AB  - A new class of triarylpyridinio-derivatized [4'-(p-phenyl)(n)]terpyridyl ligands,
      R(1)(2)R(2)TP(+)-(p)(n)tpy, was designed as a novel category of electron-acceptor
      (A)-substituted proto-photosensitizing molecules. The first elements of this
      versatile family of ligands (i.e., n = 0, 1 and R(1) = R(2) = H), H(3)TP(+)-tpy
      and H(3)TP(+)-ptpy, were synthesized as well as their Ru(II) and Os(II) complexes
      to form the related acceptor-functionalized M(tpy)(2)(2+) and M(ptpy)(2)(2+)
      photosensitizer components denoted P0 and P1, respectively. Within the P1 series
      of compounds, an electron-donor (D)-substituted ligand, Me(2)N-ptpy, was also
      involved and associated with H(3)TP(+)-ptpy, giving rise to various combinations
      (up to 10 polyad systems). The two resulting series of nanometer-scale rigid rod
      like photosensitized supramolecular architectures are of potential interest for
      long-range photoinduced electron transfer purposes. The main structural features
      of such supermolecules were determined by comparing the results obtained from (i)
      single-crystal X-ray analysis of the two free ligands together with that of the
      P0A/Ru and P1A(2)/Ru complexes and (ii) a detailed solution (1)H NMR study of the
      P0 series and, more specifically, of the P0A/Ru dyad (ROESY experiment). It is
      shown that the pseudoperpendicular conformation of the covalently linked A and P
      subunits found in the solid state is persistent in fluid medium; i.e., A is not
      conjugated with P (P0 and P1). The first insights regarding the consequences upon
      intercomponent couplings of combined substituent effects and conjugation (case of
      D-based polyads)-or absence of conjugation-are discussed in the light of ground
      state electronic properties of the compounds.

PMID- 11841307
TI  - C [bond] H activation by cationic platinum(II) complexes: ligand electronic and
      steric effects.
AB  - A series of bis(aryl)diimine-ligated methyl complexes of Pt(II) with various
      substituted aryl groups has been prepared. The cationic complexes [(ArN=CR [bond]
      CR=NAr)PtMe(L)](+)[BF(4)](-) (Ar = aryl; R = H, CH(3); L = water,
      trifluoroethanol) react smoothly with benzene at approximately room temperature
      in trifluoroethanol solvent to yield methane and the corresponding phenyl Pt(II)
      cations, via Pt(IV)-methyl-phenyl-hydrido intermediates. The reaction products of
      methyl-substituted benzenes suggest an inherent reactivity preference for
      aromatic over benzylic C [bond] H activation, which can however be overridden by
      steric effects. For the reaction of benzene with cationic Pt(II) complexes
      bearing 3,5-disubstituted aryl diimine ligands, the rate-determining step is C
      [bond] H activation, whereas for the more sterically crowded analogues with 2,6
      dimethyl-substituted aryl groups, benzene coordination becomes rate-determining.
      This switch is manifested in distinctly different isotope scrambling and kinetic
      deuterium isotope effect patterns. The more electron-rich the ligand is, as
      assayed by the CO stretching frequency of the corresponding carbonyl cationic
      complex, the faster the rate of C [bond] H activation. Although at first sight
      this trend appears to be at odds with the common description of this class of
      reaction as electrophilic, the fact that the same trend is observed for the two
      different series of complexes, which have different rate-determining steps,
      suggests that this finding does not reflect the actual C [bond] H activation
      process, but rather reflects only the relative ease of benzene displacing a
      ligand to initiate the reaction; that is, the change in rates is mostly due to a
      ground-state effect. The stability of the aquo complex ground state in
      equilibrium with the solvento complex increases as the diimine ligand is made
      more electron-withdrawing. Several lines of evidence, including the mechanism of
      degenerate acetonitrile exchange for the methyl-acetonitrile Pt(II) cations in
      alcohol solvents, suggest that associative substitution pathways operate to get
      the hydrocarbon substrate into, and out of, the coordination sphere; that is, the
      mechanism of benzene substitution proceeds by a solvent (TFE)-assisted
      associative pathway.

PMID- 11841309
TI  - Artificial lamellar mesostructures to WS(2) nanotubes.
AB  - A direct pyrolysis method from artificial lamellar mesostructures to nanotubes
      was developed for the synthesis of tungsten disulfide (WS(2)) nanotubes. In this
      process, a tungsten sulfide artificial lamellar mesostructure composite with
      intercalated cetyltrimethylammonium cations (WS-L) was prepared on the basis of
      the recently developed template self-assembly of anionic tungstates (WS(4)(2-))
      and cationic surfactant molecules (CTA(+)) in solution under appropriate
      conditions. After heating of this inorganic-surfactant lamellar composite
      material in an argon atmosphere to 850 degrees C, bulk quantities of uniform
      WS(2) nanotubes with diameters of 5-37.5 nm and lengths ranging from 0.2 to 5
      microm were produced, which revealed a general rolling mechanism of layered
      sheets for tubule formation. The observations of transmission electron microscopy
      are in good agreement with the proposed rolling mechanism.

PMID- 11841308
TI  - Electronic and medium effects on the rate of arene C [bond] H activation by
      cationic Ir(III) complexes.
AB  - A detailed mechanistic study of arene C [bond] H activation in CH(2)Cl(2)
      solution by Cp(L)IrMe(X) [L = PMe(3), P(OMe)(3); X = OTf, (CH(2)Cl(2))BAr(f);
      (BAr(f) = B[3,5-C(6)H(3)(CF(3))(2)](4))(-)] is presented. It was determined that
      triflate dissociation in Cp(L)IrMe(OTf), to generate tight and/or solvent
      separated ion pairs containing a cationic iridium complex, precedes C [bond] H
      activation. Consistent with the ion-pair hypothesis, the rate of arene activation
      by Cp(L)IrMe(OTf) is unaffected by added external triflate salts, but the rate is
      strongly dependent upon the medium. Thus the reactivity of Cp(PMe(3))IrMe(OTf)
      can be increased by almost 3 orders of magnitude by addition of (n
      Hex)(4)NBAr(f), presumably because the added BAr(f) anion exchanges with the OTf
      anion in the initially formed ion pair, transiently forming a cation/borate ion
      pair in solution (special salt effect). In contrast, addition of (n
      Hex)(4)NBAr(f) to [CpPMe(3)Ir(Me)CH(2)Cl(2)][BAr(f)] does not affect the rate of
      benzene activation; here there is no initial covalent/ionic pre-equilibrium that
      can be perturbed with added (n-Hex)(4)NBAr(f). An analysis of the reaction
      between Cp(PMe(3))IrMe(OTf) and various substituted arenes demonstrated that
      electron-donating substituents on the arene increase the rate of the C [bond] H
      activation reaction. The rate of C(6)H(6) activation by
      [Cp(PMe(3))Ir(Me)CH(2)Cl(2)][BAr(f)] is substantially faster than
      [Cp(P(OMe)(3))Ir(Me)CH(2)Cl(2)][BAr(f)]. Density functional theory computations
      suggest that this is due to a less favorable pre-equilibrium for dissociation of
      the dichloromethane ligand in the trimethyl phosphite complex, rather than to a
      large electronic effect on the C [bond] H oxidative addition transition state.
      Because of these combined effects, the overall rate of arene activation is
      increased by electron-donating substituents on both the substrate and the iridium
      complex.

PMID- 11841310
TI  - Vibrational progressions in the valence ionizations of transition metal hydrides:
      evaluation of metal-hydride bonding and vibrations in (eta(5)
      C(5)R(5))Re(NO)(CO)H [R = H, CH(3)].
AB  - The first examples of vibrational structure in metal-ligand sigma-bond
      ionizations are observed in the gas-phase photoelectron spectra of CpRe(NO)(CO)H
      and CpRe(NO)(CO)H [Cp = eta(5)-C(5)H(5), Cp = eta(5)-C(5)(CH(3))(5)]. The
      vibrational progressions are due to the Re-H stretch in the ion states formed by
      removal of an electron from the predominantly Re-H sigma-bonding orbitals. A
      vibrational progression is also observed in the corresponding ionization of the
      deuterium analogue, CpRe(NO)(CO)D, but with lower vibrational energy spacing as
      expected from the reduced mass effect. The vibrational progressions in these
      valence ionizations are directly informative about the nature of the metal
      hydride bonding and electronic structure in these molecules. Franck-Condon
      analysis shows that for these molecules the Re-H or Re-D bond lengthens by
      0.25(1) A when an electron is removed from the Re-H or Re-D sigma-bond orbital.
      This bond lengthening is comparable to that of H(2) upon ionization. Removal of
      an electron from the Re-H or Re-D bonds leads to a quantum-mechanical inner
      sphere reorganization energy (lambda(QM)) of 0.34(1) eV. These observations
      suggest that even in these low symmetry molecules the orbital corresponding to
      the Re-H sigma bond and the Re-H vibrational mode is very localized. Theoretical
      calculations of the electronic structure and normal vibrational modes of
      CpRe(NO)(CO)H support a localized two-electron valence bond description of the Re
      H interaction.

PMID- 11841311
TI  - Nucleation and growth of germanium nanowires seeded by organic monolayer-coated
      gold nanocrystals.
AB  - Germanium nanowires, ranging from 10 to 150 nm in diameter, were grown several
      micrometers in length in cyclohexane heated and pressurized above its critical
      point. Alkanethiol-protected gold nanocrystals, either 2.5 or 6.5 nm in diameter,
      were used to seed wire formation. Growth proceeded through a solution-liquid
      solid mechanism at growth temperatures ranging from 300 to 450 degrees C. At
      temperatures exceeding 500 degrees C, large Ge particulates formed due to
      unfavorable growth kinetics. Temperature, the nature of the precursor, precursor
      concentration, and the Au:Ge ratio were determining factors in nanowire
      morphology. The Ge nanowires were characterized using a range of techniques,
      including XPS, XRD, high-resolution TEM and SEM, nanometer-scale EDS mapping, and
      DTA.

PMID- 11841312
TI  - Proton-transfer dynamics in the activation of cytochrome P450eryF.
AB  - Molecular dynamics simulations are combined with quantum chemistry calculations
      of instantaneous proton-transfer energy profiles to investigate proton-transfer
      events in the transient pathway of cytochrome P450eryF (6-deoxyerythronolide B
      hydroxylase; CYP107A1), from the oxyferrous species to the catalytically active
      ferryl oxygen species (compound I). This reaction is one of the most fundamental
      unresolved aspects in the mechanism of oxidation that is common to all cytochrome
      P450s. We find that this process involves an ultrafast proton transfer from the
      crystallographic water molecule W519 to the distal oxygen bound to the heme
      group, and a subsequent proton-transfer event from W564 to W519. Both proton
      transfer events are found to be endothermic in the oxyferrous state, suggesting
      that the oxyferrous reduction is mechanistically linked to the proton-transfer
      dynamics. These findings indicate that the hydrogen bond network, proximate to
      the O(2)-binding cleft, plays a crucial functional role in the enzymatic
      activation of P450s. Our results are consistent with the effect of mutations on
      the enzymatic efficacy.

PMID- 11841313
TI  - Binding of aminoglycoside antibiotics to the small ribosomal subunit: a continuum
      electrostatics investigation.
AB  - The binding of paromomycin and similar antibiotics to the small (30S) ribosomal
      subunit has been studied using continuum electrostatics methods. Crystallographic
      information from a complex of paromomycin with the 30S subunit was used as a
      framework to develop structures of similar antibiotics in the same ribosomal
      binding site. Total binding energies were calculated from electrostatic
      properties obtained by solution of the Poisson-Boltzmann equation combined with a
      surface area-dependent apolar term. These computed results showed good
      correlation with experimental data. Additionally, calculation of the ribosomal
      electrostatic potential in the paromomycin binding site provided insight into the
      electrostatic mechanisms for aminoglycoside binding and clues for the rational
      design of more effective antibiotics.

PMID- 11841314
TI  - Slow internal dynamics in proteins: application of NMR relaxation dispersion
      spectroscopy to methyl groups in a cavity mutant of T4 lysozyme.
AB  - Recently developed carbon transverse relaxation dispersion experiments
      (Skrynnikov, N. R.; et al. J. Am. Chem. Soc. 2001, 123, 4556-4566) were applied
      to the study of millisecond to microsecond time scale motions in a cavity mutant
      of T4 lysozyme (L99A) using methyl groups as probes of dynamics. Protein
      expressed in E. coli cells with (13)CH(3)-pyruvate as the sole carbon source
      contained high levels of (13)C enrichment at a total of 80 Val gamma, Leu delta,
      Ile gamma (2), Ala beta, and Met epsilon methyl positions with little extraneous
      incorporation. Data for 72 methyl groups were available for analysis. Dispersion
      profiles with large amplitudes were measured for many of these residues and were
      well fit to a two-state exchange model. The interconversion rates and populations
      of the states, obtained from fitting relaxation dispersion profiles of each
      individual probe, were remarkably homogeneous and data for nearly all methyl
      groups in the protein could be collectively fit to a single cooperative
      conformational transition. The present study demonstrates the general
      applicability of methyl relaxation dispersion measurements for the investigation
      of millisecond time scale protein motions at a large number of side-chain
      positions. Potential artifacts associated with the experiments are described and
      methods to minimize their effects presented. These experiments should be
      particularly well suited for probing dynamics in high molecular weight systems
      due to the favorable NMR spectroscopic properties of methyl groups.

PMID- 11841315
TI  - Structural study of three isomers of Tm@C(82) by (13)C NMR spectroscopy.
AB  - The (13)C NMR spectra were measured for three isomers of Tm@C(82), which is one
      of the divalent metallofullerenes. The molecular symmetries were determined for
      each isomer: isomer I has C(s) symmetry, isomer II has C(2) symmetry, and isomer
      III has C(2v) symmetry. Moreover the cage structure of Tm@C(82)(III) was found to
      be C(82)(9). As a result, it was revealed that Tm@C(82)(III) has a cage identical
      to that of La@C(82), which is one of the trivalent metallofullerenes.

PMID- 11841316
TI  - Dihydroazulene/vinylheptafulvene photochromism: a model for one-way
      photochemistry via a conical intersection.
AB  - Dihydroazulene (DHA)/vinylheptafulvene (VHF) photochromism has been investigated
      by studying the isomerization of 1,2,3,8a,9-pentahydrocyclopent[a]azulene-9,9
      dicarbonitrile through complete active space-self consistent field calculations
      on the ground (S(0)) and first excited (S(1)) states of smaller model compounds.
      In each case, the S(1) reaction coordinate is characterized by a transition
      structure for adiabatic ring opening, connecting a DHA-like intermediate to a
      much more stable VHF-like structure. This VHF-like structure is not a real S(1)
      minimum but a crossing (i.e., a conical intersection) between the excited- and
      ground-state potential energy surfaces. The existence of such a crossing is
      consistent with the lifetime of approximately 600 fs recently measured for the
      DHA-like intermediate on S(1) (Ern, J.; Petermann, M.; Mrozek, T.; Daub, J.;
      Kuldova, K.; Kryschi, C. Chem. Phys. 2000, 259, 331-337). The shape of the
      crossing is also crucial; it not only explains the fact that the quantum yield
      approaches 1.0 for the forward DHA --> VHF reaction, but also the lack of any
      fluorescence or photochemical back-reaction from VHF. These findings are
      supported by ab initio direct dynamics calculations. This work suggests that
      calculating and understanding the topology of excited-state potential energy
      surfaces will be useful in designing photochromic molecules.

PMID- 11841317
TI  - Theoretical study of ammonia and methane activation by first-row transition metal
      cations M(+) (M = Ti, V, Cr).
AB  - The potential energy surfaces for the reaction of first-row transition metal
      cations Ti(+)((4)F,(2)F), V(+)((5)D,(3)F), and Cr(+)((6)S,(4)D) with NH(3) and
      CH(4) have been built up by using density functional theory. In all cases, the
      high-spin ion-dipole complex, which is the most stable species on the respective
      potential energy hypersurfaces, is initially formed. In the second step, a
      hydrogen shift process leads to the formation of the insertion products, which
      are more stable in a low-spin state. From these intermediates three dissociation
      channels have been considered. All the results have been compared with existing
      experimental and theoretical data and our earlier work on the reactivity of
      Sc(+), to clarify similarities and differences in the behavior of the transition
      metal ions considered.

PMID- 11841318
TI  - Carbon [bond] hydrogen bond activation by titanium imido complexes. Computational
      evidence for the role of alkane adducts in selective C [bond] H activation.
AB  - This paper reports calculations that probe the role of R (hydrocarbon) and R'
      (ligand substituent) effects on the reaction coordinate for C [bond] H
      activation: Ti(OR')(2)(=NR') + RH --> adduct --> transition state -->
      (OR')(2)Ti(N(H)R')(R). Compounds with R = H, Me, Et, Vy, cPr, Ph, Cy, Bz, and
      cubyl are studied using quantum (R' = H, SiH(3), SiMe(3)) and classical (R' =
      Si(t)Bu(3)) techniques. Calculated geometries are in excellent agreement with
      data for experimental models. There is little variability in the calculated
      molecular structure of the reactants, products, and most interestingly,
      transition states as R and R' are changed. Structural flexibility is greatest in
      the adducts Ti(OR')(2)(=NR')...HR. Despite the small structural changes observed
      for Ti(OR')(2)(double bond] NR') with different R', significant changes are
      manifested in calculated electronic properties (the Mulliken charge on Ti becomes
      more positive and the Ti [double bond] N bond order decreases with larger R'),
      changes that should facilitate C [bond] H activation. Substantial steric
      modification of the alkane complex is expected from R [bond] R' interactions,
      given the magnitude of Delta G(add) and the conformational flexibility of the
      adduct. Molecular mechanics simulations of Ti(OSi(t)Bu(3))(2)([double bond]
      NSi(t)Bu(3))...isopentane adducts yield an energy ordering as a function of the
      rank of the C [bond] H bond coordinated to Ti that is consistent with
      experimental selectivity patterns. Calculated elimination barriers compare very
      favorably with experiment; larger SiH(3) and TMS ligand substituents generally
      yield better agreement with experiment, evidence that the modeling of the major
      contributions to the elimination barrier (N [bond] H and C [bond] H bond making)
      is ostensibly correct. Calculations indicate that weakening the C [bond] H bond
      of the hydrocarbon yields a more strongly bound adduct. Combining the different
      conclusions, the present computational research points to the adduct,
      specifically the structure and energetics of the substrate/Ti-imido interaction,
      as the main factor in determining the selectivity of hydrocarbon (R) C [bond] H
      activation.

PMID- 11841319
TI  - Self-discrimination of enantiomers in hydrogen-bonded dimers.
AB  - The homochiral and heterochiral hydrogen-bonded (HB) dimers of a set of small
      model molecules (alpha-amino alcohols) have been studied by means of ab initio
      methods. The gas-phase calculations have been carried out with the hybrid HF/DFT
      B3LYP method and the 6-311++G** basis set. The electron density of the complexes
      has been analyzed using the atoms in molecules (AIM) methodology, which allows
      characterization of the HB interactions and additional intermolecular contacts.
      To take into account the water solvation effect, the polarized continuum model
      (PCM) method has been used to evaluate the Delta G(solv). The gas-phase results
      show that the heterochiral dimers are the most stable ones for each case studied,
      while in solution for several cases, the relative stability is reversed and the
      homochiral dimers become more stable. The AIM analysis shows the typical bond
      critical points characteristic of the HB and additional bond critical points
      denoting, in this case, destabilization of intermolecular interaction as
      CF(3)...F(3)C and CH(3)...H(3)C contacts.

PMID- 11841320
TI  - On the hardness evaluation in solvent for neutral and charged systems.
AB  - The influence of water on the hardness values of a series of neutral and charged
      molecules has been studied in the framework of density functional theory using
      the polarizable continuum model to take into account solvent effects. Three
      working formulas already widely tested in gas-phase have been used and the
      results compared. Two of the methods employed going from gas phase to solvent
      phase give values that do not change, while the results of the third method show
      remarkable changes. To check the reliability of the hardness behavior found, a
      test based on the hard-soft/acid-base principle and the calculation of the free
      energy of reaction has been applied using the adopted procedures.

PMID- 11841321
TI  - The short N [bond] F bond in N(2)F(+) and how Pauli repulsion influences bond
      lengths. Theoretical study of N(2)X(+), NF(3)X(+), and NH(3)X(+) (X [double bond]
      F, H).
AB  - Exceptionally short N [bond] F bond distances of only 1.217 A (crystal) and 1.246
      A (gas phase) have been reported for N(2)F(+), making it the shortest N [bond] F
      bond ever observed. To trace the origin of this structural phenomenon, we have
      analyzed the model systems N(2)X(+), NF(3)X(+), and NH(3)X(+) (X [double bond] F,
      H) using generalized gradient approximation density functional theory at
      BP86/TZ2P. In good agreement with experiment, the computations yield an extremely
      short N [bond] F bond for N(2)F(+): we find N [bond] F bond distances in
      N(2)F(+), NF(4)(+), and NH(3)F(+) of 1.245, 1.339, and 1.375 A, respectively. The
      N [bond] X bonding mechanisms are quantitatively analyzed in the framework of
      Kohn-Sham MO theory. At variance with the current hypothesis, reduced steric and
      other Pauli repulsion (of substituents or lone pairs at N with F) rather than the
      extent of s [bond] p hybridization of N (i.e., sp versus sp(3)) are responsible
      for the much shorter N [bond] F distance in N(2)F(+) compared to NF(4)(+). The
      results for our nitrogen compounds are furthermore discussed in the more general
      context of how bond lengths are determined by both bonding and repulsive orbital
      interactions.

PMID- 11841322
TI  - Hydrogen bond versus polar effects: an ab initio analysis on n --> pi* absorption
      spectra and N nuclear shieldings of diazines in solution.
AB  - The complex nature of the effect of H-bonding solvents on electronic and magnetic
      properties of diazines in dilute solution is analyzed by comparing results
      obtained with continuum, discrete, and mixed continuum-discrete solvation
      methods. For comparison, other, nonprotic solvents are also considered. The
      interpretation of the results shows that strong H-bonding effects, such as those
      exerted by water molecules on diazines nitrogens, are accompanied by comparable
      (or at least not negligible) long-range polar interactions. It is also shown that
      a continuum model not only well describes such "bulk effects" but becomes
      essential to get the correct description of the interactions due to explicit H
      bonded molecules. This double action (direct, as an additional long-range field,
      and indirect, through the H-bonded molecules) significantly modifies the solute
      electronic and nuclear charge distribution and the related response properties.
      This picture is confirmed by an NBO analysis on single diazines and the
      corresponding H-bonded clusters with and without an external continuum solvent.

PMID- 11841323
TI  - How to insulate a reactive site from a perfluoroalkyl group: photoelectron
      spectroscopy, calorimetric, and computational studies of long-range electronic
      effects in fluorous phosphines P((CH(2))(m)(CF(2))(7)CF(3))(3).
AB  - This study advances strategy and design in catalysts and reagents for fluorous
      and supercritical CO(2) chemistry by defining the structural requirements for
      insulating a typical active site from a perfluoroalkyl segment. The vertical
      ionization potentials of the phosphines P((CH(2))(m)R(f8))(3) (m = 2 (2) to 5
      (5)) are measured by photoelectron spectroscopy, and the enthalpies of
      protonation by calorimetry (CF(3)SO(3)H, CF(3)C(6)H(5)). They undergo
      progressively more facile (energetically) ionization and protonation
      (P(CH(2)CH(3))(3) > 5 > 4 approximately equal to P(CH(3))(3) > 3 > 2), as
      expected from inductive effects. Equilibrations of trans-Rh(CO)(Cl)(L)(2)
      complexes (L = 2, 3) establish analogous Lewis basicities. Density functional
      theory is used to calculate the structures, energies, ionization potentials, and
      gas-phase proton affinities (PA) of the model phosphines P((CH(2))(m)()CF(3))(3)
      (2'-9'). The ionization potentials of 2'-5' are in good agreement with those of 2
      5, and together with PA values and analyses of homodesmotic relationships are
      used to address the title question. Between 8 and 10 methylene groups are needed
      to effectively insulate a perfluoroalkyl segment from a phosphorus lone pair,
      depending upon the criterion employed. Computations also show that the first
      carbon of a perfluoroalkyl segment exhibits a much greater inductive effect than
      the second, and that ionization potentials of nonfluorinated phosphines
      P((CH(2))(m)CH(3))(3) reach a limit at approximately nine carbons (m = 8).

PMID- 11841325
TI  - Hierarchical self-assembly of amphiphilic metallohosts to give discrete
      nanostructures.
AB  - The synthesis and aggregation behavior of a new class of rigid metallohosts is
      described. The molecules consist of a ruthenium-bipyridine complex functionalized
      with a glycoluril-based receptor cavity. By specific molecular recognition
      processes in water, the metallohosts self-assemble to form large arrays of
      molecules. Depending on the size of the cavity side walls of the host, these
      arrays can grow in a hierarchical process into discrete rectangular and cigar
      like aggregates of nanometer size, which can be visualized by electron
      microscopy.

PMID- 11841324
TI  - Dynamics of energy transfer in peptide-surface collisions.
AB  - Classical trajectory simulations are performed to study energy transfer in
      collisions of protonated triglycine (Gly)(3) and pentaglycine (Gly)(5) ions with
      n-hexyl thiolate self-assembled monolayer (SAM) and diamond [111] surfaces, for a
      collision energy E(i) in the range of 10-110 eV and a collision angle of 45
      degrees. Energy transfer to the peptide ions' internal degrees of freedom is more
      efficient for collision with the diamond surface; i.e., 20% transfer to peptide
      vibration/rotation at E(i) = 30 eV. For collision with diamond, the majority of
      E(i) remains in peptide translation, while the majority of the energy transfer is
      to surface vibrations for collision with the softer SAM surface. The energy
      transfer efficiencies are very similar for (Gly)(3) and (Gly)(5). Constraining
      various modes of (Gly)(3) shows that the peptide torsional modes absorb
      approximately 80% of the energy transfer to the peptide's internal modes. The
      energy-transfer efficiencies depend on E(i). These simulations are compared with
      recent experiments of peptide SID and simulations of energy transfer in
      Cr(CO)(6)(+) collisions with the SAM and diamond surfaces.

PMID- 11841326
TI  - Phosphorus chemical shift tensors of phosphido ligands in ruthenium carbonyl
      compounds: (31)P NMR spectroscopy of single-crystal and powder samples and ab
      initio calculations.
AB  - The phosphorus chemical shift (CS) tensors of several ruthenium carbonyl
      compounds containing a phosphido ligand, micro), bridging a Ru [bond] Ru bond
      were characterized by solid-state (31)P NMR spectroscopy. As well, an analogous
      osmium compound was examined. The structures of most of the clusters investigated
      have approximate local C(2v) symmetry about the phosphorus atom. Compared to the
      "isolated" PH(2)(-) anion, the phosphorus nucleus of a bridging phosphido ligand
      exhibits considerable deshielding. The phosphorus CS tensors of most of the
      compounds have spans ranging from 230 to 350 ppm and skews of approximately zero.
      Single-crystal NMR was used to investigate the orientation of the phosphorus CS
      tensors for two of the compounds, Ru(2)(CO)(6)(mu(2)-C [triple bond] C [bond]
      Ph)(mu(2)-PPh(2)) and Ru(3)(CO)(9)(mu(2)-H)(mu(2)-PPh(2)). The intermediate
      component of the phosphorus CS tensor, delta(22), lies along the local C(2) axis
      in both compounds. The least shielded component, delta(11), lies perpendicular to
      the Ru [bond] P [bond] Ru plane while the most shielded component, delta(33),
      lies perpendicular to the C [bond]P [bond] C plane. The orientation of the
      phosphorus CS tensor for a third compound, Ru(2)(CO)(6)(mu(2)-PPh(2))(2), was
      investigated by the dipolar-chemical shift NMR technique and was found to be
      analogous, suggesting it to be the same in all compounds. Ab initio calculations
      of phosphorus magnetic shielding tensors have been carried out and reproduce the
      orientations found experimentally. The orientation of the CS tensor has been
      rationalized using simple frontier MO theory. Splittings due to (99,101)Ru [bond]
      (31)P spin-spin coupling have been observed for several of the complexes. A rare
      example of (189)Os [bond] (31)P spin-spin splittings is observed in the (31)P MAS
      NMR spectrum of the osmium cluster, where (1)J((189)Os, (31)P) is 367 Hz. For
      this complex, the (189)Os nuclear quadrupolar coupling constant is on the order
      of several hundred megahertz.

PMID- 11841336
TI  - Contact system. New concepts on activation mechanisms and bioregulatory
      functions.
AB  - This review considers the data of recent years concerning the contact system
      initiating the activation of blood plasma proteolytic systems, such as
      hemocoagulation, fibrinolysis, kininogenesis, and also complement and
      angiotensinogenesis. The main proteins of the contact system are the factors XII
      and XI, prekallikrein, and high-molecular-weight kininogen. The data on the
      structure, functions, and biosynthesis of these proteins and on their genes are
      presented. Studies in detail on the protein-protein interactions during formation
      of the ensemble of the contact system components on the anionic surface resulted
      in the postulation of the mechanism of activation of this system associated with
      generation of the XIIa factor and of kallikrein. This mechanism is traditionally
      considered a trigger of processes for the internal pathway of the hemocoagulating
      cascade. However, the absence of direct confirmation of such activation in vivo
      and the absence of hemorrhagia in the deficiency of these components stimulated
      the studies designed to find another mechanism of their activation and
      physiological role outside of the hemostasis system. As a result, a new concept
      on the contact system activation on the endothelial cell membrane was proposed.
      This concept is based on the isolation of a complex of proteins, which in
      addition to the above-mentioned proteins includes cytokeratin 1 and the receptors
      of the urokinase-like plasminogen activator and of the complement q-component.
      The ideas on the role of this system in the biology of vessels are developed.
      Some of our findings on the effect of leukocytic elastase on the key components
      of the contact system are also presented.

PMID- 11841335
TI  - Blood coagulation.
AB  - The process of tissue factor initiated blood coagulation is discussed. Reactions
      of the blood coagulation cascade are propagated by complex enzymes containing a
      vitamin K-dependent serine protease and an accessory cofactor protein that are
      assembled on a membrane surface in a calcium-dependent manner. These complexes
      are 105-109-fold more efficient in proteolyses of their natural substrates than
      enzymes alone. Based upon data acquired using several in vitro models of blood
      coagulation, tissue factor initiated thrombin generation can be divided into two
      phases: an initiation phase and a propagation phase. The initiation phase is
      characterized by the generation of nanomolar amounts of thrombin, femto- to
      picomolar amounts of factors VIIa, IXa, Xa, and XIa, partial activation of
      platelets, and almost quantitative activation of procofactors, factors V and
      VIII. The duration of this phase is primarily influenced by concentrations of
      tissue factor and TFPI. The characteristic features of the propagation phase are:
      almost quantitative prothrombin activation at a high rate, completion of platelet
      activation, and solid clot formation. This phase is primarily regulated by
      antithrombin III and the protein C system. Thrombin generation during the
      propagation phase is remarkably suppressed in the absence of factor VIII and IX
      (hemophilia A and B, respectively) and at platelet counts <5% of mean plasma
      concentration. The majority of data accumulated in in vitro models and discussed
      in this review are in good agreement with the results of in vivo observations.

PMID- 11841337
TI  - Gene targeting of tissue factor, factor X, and factor VII in mice: their
      involvement in embryonic development.
AB  - Inactivation of specific genes in mammals by gene targeting has accelerated our
      ability to determine gene function. Nearly all genes involved in the blood
      coagulation system have been knocked out in mice. Tissue factor (TF) is the main
      initiator of the coagulation system and functions as a cell surface receptor for
      coagulation factor VII (FVII). Knockout studies have shown that TF deficiency
      results in lethality around embryonic day (E) 8.5-10.5. The results suggest a
      role for TF in embryonic blood vessel development and maintenance of vascular
      integrity in the yolk sac. In addition, TF may be involved in the maintenance of
      the placental labyrinth. Factor X (FX) deficiency causes partial embryonic
      lethality between E11.5-12.5. FX-/- mice that were born died from fatal neonatal
      bleeding. In contrast, FVII deficiency is not embryonic lethal, but FVII-/-
      neonates died from hemorrhage within the first days after birth. The various
      lethal phenotypes of deficiencies of the different coagulation factors suggest
      involvement in processes beyond hemostasis. Both TF/FVIIa and FXa can trigger
      intracellular signaling events in certain cell types. Signaling by coagulation
      proteases and protease-activated receptors (PARs) may have important roles in
      embryonic development.

PMID- 11841338
TI  - Genetic mechanisms of hereditary hemostasis disorders.
AB  - This review summarizes known human genes whose mutations are associated with
      inherited hemostasis defects. These genes are divided into three groups. The
      genes of the first group are responsible for platelet adhesion, activation, and
      aggregation. The genes of the second group control the biosynthesis of blood
      clotting factors and cofactors. The genes of the third group are required for the
      functioning of proteins involved in the anticoagulant system and fibrinolysis.

PMID- 11841339
TI  - The blood platelet as a model for regulating blood coagulation on cell surfaces
      and its consequences.
AB  - Platelets actively participate in regulating thrombin production following
      physical or chemical injury to blood vessels. Injury to blood vessels initiates
      activation of the large numbers of platelets that appear in the subendothelium
      where they become exposed to tissue factor and to molecules adhesive for
      platelets and normally found in the extracellular matrix. The complex of plasma
      factor VIIa with extravascular tissue factor both initiates and localizes
      thrombin production on platelets and on extravascular cells. Thrombin production
      at these sites in turn enhances platelet activation and the subsequent hemostatic
      plug formation to minimize bleeding. Thrombin production and platelet activation
      also initiate the process of wound healing requiring thrombin-dependent cell
      activation and platelet-dependent formation of new blood vessels (angiogenesis).
      Activated platelets release from their storage granules several proteins and
      other factors that regulate local thrombin formation and the responses of blood
      vessel cells to injury to assure hemostasis and effective wound healing. Failure
      to localize and adequately regulate thrombin production and/or platelet
      activation can have pathological consequences, including the development and
      propagation of atherosclerosis and enhancement of tumor development. The primary
      basis for the pathological consequences of the failure to adequately regulate
      thrombin production is that the multi-functional thrombin activates several types
      of cells to initiate their mitogenesis. Mitogenesis precedes many of the
      undesirable consequences of poorly regulated thrombin production and platelet
      activation. In addition, activated platelets release a variety of products which
      influence the functions of several cell types to the extent that inadequate
      regulation of platelet activation (by excessive thrombin production) could
      contribute to the pathogenesis of acute and chronic arterial thrombosis and to
      tumor development. Activated platelets participate in tumor development by
      releasing several factors that positively (and negatively) regulate blood vessel
      formation.

PMID- 11841340
TI  - Thrombin regulation of cell function through protease-activated receptors:
      implications for therapeutic intervention.
AB  - The serine protease thrombin is well recognized as being pivotal to the
      maintenance of hemostasis under both normal and pathological conditions. Its
      cellular actions are mediated through a unique family of protease-activated
      receptors (PARs). These receptors represent a novel family of G protein-coupled
      receptors that undergo proteolytic cleavage of their amino terminus and
      subsequent autoactivation by a tethered peptide ligand. This paper reviews the
      consequences of PAR activation in thrombosis, vascular injury, inflammation,
      tissue injury, and within the tumor microenvironment.

PMID- 11841341
TI  - Receptors of the PAR family as a link between blood coagulation and inflammation.
AB  - Blood coagulation plays a key role among numerous mediating systems that are
      activated in inflammation. Receptors of the PAR family serve as sensors of serine
      proteinases of the blood clotting system in the target cells involved in
      inflammation. Activation of PAR-1 by thrombin and of PAR-2 by factor Xa leads to
      a rapid expression and exposure on the membrane of endothelial cells of both
      adhesive proteins that mediate an acute inflammatory reaction and of the tissue
      factor that initiates the blood coagulation cascade. Certain other receptors (EPR
      1, thrombomodulin, etc.), which can modulate responses of the cells activated by
      proteinases through PAR receptors, are also involved in the association of
      coagulation and inflammation together with the receptors of the PAR family. The
      presence of PAR receptors on mast cells is responsible for their reactivity to
      thrombin and factor Xa and defines their contribution to the association of
      inflammation and blood clotting processes.

PMID- 11841342
TI  - Molecular mechanisms of thrombin-induced endothelial cell permeability.
AB  - Confluent endothelium serves as a selective barrier between the vascular space of
      blood vessels and underlying tissues. Compromised barrier function of the
      endothelium in response to inflammation mediators, such as thrombin, is
      accompanied by reversible cell rounding and interendothelial gap formation.
      Endothelial barrier integrity substantially depends on the cytoskeleton, which
      ensures actin stress fiber formation and via actomyosin-driven contraction
      regulates cell shape and adhesion. Recent studies have shown the sequence of
      events that mediate signal transduction in endothelial cells. Binding of thrombin
      with its receptor initiates activation of heterotrimeric G-proteins, which, in
      turn, entails a decrease in cAMP level in the cell, increase in intracellular
      Ca2+ and diacylglycerol concentration, and activation of the small G-protein Rho.
      Phosphorylation of myosin light chains as a result of activation of myosin light
      chain kinase and inactivation of myosin phosphatases stimulates stress fiber
      formation and triggers actomyosin contraction. In addition, thrombin-induced
      rearrangement in the endothelial cytoskeleton is regulated by Ca2+/calmodulin
      dependent protein kinase, protein kinase C, and tyrosine protein kinases. This
      review focuses on presently known biochemical mechanisms of cell response to
      thrombin and their role in endothelial barrier dysfunction.

PMID- 11841343
TI  - Statin drugs and dietary isoprenoids downregulate protein prenylation in signal
      transduction and are antithrombotic and prothrombolytic agents.
AB  - Statins and various isoprenoids of dietary origins inhibit L-mevalonic acid
      synthesis, which in turn downregulates cholesterol and various other dependent
      substances, including farnesyl- and geranylgeranyl-conjugated proteins involved
      in cell signaling processes. Such signaling processes are stimulated by protease
      activated receptor-1 (PAR-1), which upon activation, causes the expression of
      various substances including tissue factor (TF) and plasminogen activator
      inhibitor-1 (PAI-1). Tissue factor promotes thrombin generation, where thrombin
      stimulates a variety of cellular processes, as well as activating PAR-1 to
      produce more thrombin. Statins downregulate TF mitigating thrombin generation and
      also downregulate PAI-1, which normally consumes tissue plasminogen activator
      (tPA). In the absence of PAI-1, tPA activates plasminogen to generate plasmin.
      Thus, statins behave as antithrombotic agents and prothrombolytic agents.

PMID- 11841344
TI  - Matrix metalloproteinases and cellular fibrinolytic activity.
AB  - Several molecular interactions between the matrix metalloproteinase (MMP) and the
      plasminogen/plasmin (fibrinolytic) system may affect cellular fibrinolysis. MMP-3
      (stromelysin-1) specifically hydrolyzes urokinase (u-PA), yielding a 17 kD NH2
      terminal fragment containing the functionally intact receptor (u-PAR)-binding
      sequence and a 32 kD COOH-terminal fragment containing the intact serine
      proteinase domain. MMP-3 generates an angiostatin-like fragment (containing
      kringles 1-4 with the cellular binding domains) from plasminogen. Treatment with
      MMP-3 of monocytoid THP-1 cells saturated with bound plasminogen, resulted in a
      dose-dependent reduction of the amount of u-PA-activatible plasminogen. Treatment
      with MMP-3 of cell-bound u-PA, in contrast, did not alter cell-associated u-PA
      activity. These data thus indicate that MMP-3 may downregulate cell-associated
      plasmin activity by decreasing the amount of activatible plasminogen, without
      affecting cell-bound u-PA activity. MMP-3 also specifically interacts with the
      main inhibitors of the fibrinolytic system. Thus, MMP-3 specifically hydrolyzes
      human alpha2-antiplasmin (alpha2-AP), the main physiological plasmin inhibitor.
      alpha2-AP cleaved by MMP-3 no longer forms a stable complex with plasmin and no
      longer interacts with plasminogen. Cleavage and inactivation of alpha2-AP by MMP
      3 may constitute a mechanism favoring local plasmin-mediated proteolysis.
      Furthermore, MMP-3 specifically hydrolyzes and inactivates human plasminogen
      activator inhibitor-1 (PAI-1). Stable PAI-1 bound to vitronectin is cleaved and
      inactivated by MMP-3 in a comparable manner as free PAI-1; the cleaved protein,
      however, does not bind to vitronectin. Cleavage and inactivation of PAI-1 by MMP
      3 may thus constitute a mechanism decreasing the antiproteolytic activity of PAI
      1 and impairing the potential inhibitory effect of vitronectin-bound PAI-1 on
      cell adhesion and/or migration. These molecular interactions of MMP-3 with
      enzymes, substrates and inhibitors of the fibrinolytic system may thus play a
      role in the regulation of (cellular) fibrinolysis. Furthermore, the temporal and
      topographic expression pattern of MMP components, as well as studies in gene
      deficient mice, suggest a functional role in neointima formation after vascular
      injury.

PMID- 11841345
TI  - The fibrinolysis system: regulation of activity and physiologic functions of its
      main components.
AB  - This review summarizes basic properties and mechanisms of activation and
      inhibition of main components of the fibrinolytic system that, acting in accord
      with the system of blood coagulation, provides temporal formation of fibrin clots
      at sites of vascular injury for the time required for the regeneration of
      vascular wall. Impairments in the fibrinolytic system may cause bleedings or
      thrombotic complications in patients. The predictive value of some components of
      the fibrinolytic system with respect to the development of complications of
      atherothrombosis is considered.

PMID- 11841346
TI  - Urokinase as a multidomain protein and polyfunctional cell regulator.
AB  - The urokinase type plasminogen activator (urokinase) plays a pivotal role in the
      regulation of cell adhesion and migration during tissue remodeling. Urokinase not
      only specifically cleaves plasminogen and converts it into plasmin but also
      activates intracellular signaling upon binding to certain receptors on the cell
      surface. The polyfunctional properties of this protein are associated with its
      three-domain structure as follows: the C-terminal proteolytic domain containing
      the serine protease active center, the central kringle domain, and the N-terminal
      domain homologous to epidermal growth factor. This review considers functional
      properties of urokinase and of its fragments generated on the cell surface as a
      result of proteolytic processing. This review will discuss the mechanisms of
      urokinase-mediated regulation of cellular function upon binding to membrane
      receptors.

PMID- 11841347
TI  - Plasminogen activators in vascular remodeling and angiogenesis.
AB  - This review considers cellular and molecular mechanisms of the involvement of
      plasminogen activators in extracellular proteolysis and cell migration and
      proliferation. The role of plasminogen activators in vascular remodeling in
      atherosclerosis, restenosis, and angiogenesis is discussed.

PMID- 11841348
TI  - Fibrinogen-fibrin system regulators from bloodsuckers.
AB  - Thrombin inhibitors from bloodsucking leeches and insects that block conversion
      of fibrinogen to fibrin are considered. Regulatory mechanisms influencing the
      fibrinogen-fibrin system in leeches include fibrinogen degradation, inhibition of
      factor XIIIa, and lysis of fibrin clots. The review also summarizes recent data
      on plasminogen activator from the vampire bat Desmodus rotundus and a role of
      fibrin as its cofactor.

PMID- 11841349
TI  - Vascular-platelet and plasma hemostasis regulators from bloodsucking animals.
AB  - Saliva of bloodsuckers (leeches, insects, ticks, vampire bats) contains various
      regulators of some hemostatic stages. This review summarizes information on their
      structural characteristics and mechanisms of action. Most bloodsuckers are shown
      to inhibit vascular-platelet hemostasis by blocking collagen-induced platelet
      adhesion/aggregation. Plasma hemostasis is inhibited by blocking activation of
      factor X or factor Xa directly.

PMID- 11841351
TI  - Adrenergic and cholinergic innervation of the mammary gland in the pig.
AB  - Adrenergic and acetylcholinesterase-positive (AChE-positive) innervation of the
      mammary gland in the sexually immature and mature pigs was studied using
      histochemical methods. Upon examining the adrenergic and cholinergic innervation,
      the adrenergic innervation was found to be much more developed. The majority of
      both sub-populations of the nerve fibres studied was localized in the
      subcutaneous tissue of the mammary gland. Adrenergic and AChE-positive nerve
      fibres also supplied structures of the nipple (subcutaneous tissue, blood
      vessels, smooth muscles fibres) and glandular tissue (blood vessels, lactiferous
      ducts). The glandular tissue contained the smallest number of adrenergic and AChE
      positive nerve fibres. No distinct differences were observed in the adrenergic
      and AChE-positive innervation of the porcine mammary gland between the juvenile
      and non-pregnant adult animals.

PMID- 11841352
TI  - Epithelial cell proliferation and apoptosis in the developing murine palatal
      rugae.
AB  - Epithelial cell proliferation and apoptosis during morphogenesis of the murine
      palatal rugae (PR) were examined histochemically by using anti-bromodeoxyuridine
      (BrdU) and the terminal deoxynucleotidyl transferase-mediated UTP nick-end
      labelling (TUNEL) technique. Formation of the PR rudiment was observed as an
      epithelial placode in fetuses at 12.5 days post-coitus (dpc). During the PR
      formation, BrdU-positive cells were detected mainly in the epithelium of the
      interplacode and interprotruding areas in fetuses administered BrdU maternally at
      2 h before killing. TUNEL-positive cells were detected only at the epithelial
      placode area in 12.5-14.5 dpc. At 16.5-18.5 dpc, the BrdU-positive cells were
      decreased in number in the epithelial cells at the interprotruding area of the
      PR. Only a few TUNEL-positive cells were observed in the protruding area of the
      PR at 16.5 dpc. These results suggest that cell proliferation and apoptosis in
      the palatal epithelium are involved spatiotemporally in the murine PR
      morphogenesis.

PMID- 11841353
TI  - Effects of dimecron on developing chick embryo: malformations and other
      histopathological changes.
AB  - The effect of dimecron, an organophosphorus insecticide, on developmental
      alterations and histopathological damage was determined in the developing chick
      embryo. The insecticide was administered at two different doses (25 microg and 35
      microg) into the egg yolk through a pore into the equatorial region at day 0 of
      incubation. Significant abnormalities in relation to organogenesis and overall
      retardation in growth were noted in the insecticide-treated embryos.
      Histopathological study of the treated whole embryo showed abnormal features in
      the formation of different vital organs. The liver and kidney were severely
      affected by the pesticide at both doses. Based upon these findings it may be
      concluded that dimecron does play a role in producing embryotoxicity at different
      stages of embryogenesis.

PMID- 11841354
TI  - A morphometric study of the structural characteristics of the aorta in pigs using
      an image analysis method.
AB  - The objective of this study was to evaluate multiple structural characteristics,
      in addition to vasa vasorum density, in different aortic regions. The aorta of
      healthy Landrace pigs was divided into four thoracic and three abdominal
      segments. Transverse sections were reserved for morphometric analysis. Image
      analysis showed the aortic diameter, the thickness of the media, the number of
      elastic lamellae and the thickness of elastic membranes being reduced with
      increased distance from the heart (P < 0.05). The average thickness of lamellar
      units remained constant in the thoracic, but increased in the abdominal aorta (P
      < 0.05). The number of lamellar units, contained in the avascular zone of the
      media, and the density of vasa vasorum decreased peripherally (P < 0.05), still
      the average thickness of the avascular zone was invariant. In conclusion, the
      anatomical properties of the vessel wall alter through the aorta, being optimal
      for the varying stresses to which the aorta is subjected along its length. The
      distinct aortic parts may exhibit inherent morphological features, responsible
      for the various pathological processes that affect the aorta.

PMID- 11841355
TI  - Labelling of rat endothelial cells with antibodies to vWF, RECA-1, PECAM-1, ICAM
      1, OX-43 and ZO-1.
AB  - Labelling with endothelium specific monoclonal antibodies, von Willebrand Factor
      (vWF), rat endothelial cell antigen-1 (RECA-1), platelet-endothelial cell
      adhesion molecule-1 (PECAM-1), intercellular adhesion molecule-1 (ICAM-1), OX-43
      and zonula occludentes-1 (ZO-1), was investigated in cryostat sections of vessels
      from rats of different ages using a confocal microscope. The results showed that
      labelling of the vWF was positive in endothelial cells from adult, fetal and
      different ages of embryonic rat. Labelling with RECA-1 was weakly positive in
      adult rat aorta and lung endothelial cells but not in embryonic yolk sac
      endothelial cells. Labelling using PECAM-1, ICAM-1 and OX-43 was negative in both
      adult and embryonic endothelial cells. ZO-1 showed positive but very weak
      reactivity in embryonic yolk sac endothelial cells. The expression of vWF on
      vessels from adult and 19.5-day fetal tissues was strongly positive. However, the
      expression of vWF in embryonic endothelial cells was dependent on the gestational
      age. While the 11.5-day yolk sac vessels stained weakly, staining gradually
      increased in 13.5-, 15.5- and 17.5-day-old yolk sac vessels. The results suggest
      that vWF is a reliable endothelial cell marker in rat vascular endothelial cells,
      including both fetal and embryonic stages.

PMID- 11841356
TI  - Periods and stages of the prenatal development of the domestic cat.
AB  - Twenty-two stages of the prenatal development of the domestic cat are described
      for intraspecies comparison in embryological studies. These are assigned to the
      15 embryonal periods based on the Nomina Embryologica Veterinaria to make the
      interspecies comparison possible.

PMID- 11841357
TI  - [The origin and function of the enamel cup, infundibulum dentis, on the incisors
      of the horse].
AB  - The enamel cups of equids originated phylogenetically through several phases in
      Oligocene and Miocene horses, which readjusted from hard to soft leaf food and
      from double nutrition (leaves and grass) to a pure grass intake. This has been
      proved experimentally. The resulting construction of the incisor is continually
      changed on its occlusal surface by erosion according to the pattern of the enamel
      crests. Referring to the whole incisor tooth, this results in an equid life cycle
      in which the good grip of the occlusal surface and the efficiency of ingestion
      favours the young, sexually mature horses, which are at the best age for food
      intake.

PMID- 11841358
TI  - Involution of bursa cloacalis (Fabricii) and thymus in Cyclosporin A-treated
      chickens.
AB  - Fifty-day-old Arbor Acres chickens received a daily oral dose of 30 mg/kg
      Cyclosporin A for 21 consecutive days. This treatment induced the striking
      morphological changes in the bursa cloacalis (Fabricii). The number of bursal
      follicles did not change, but they were markedly decreased in size. The pars
      lymphoreticularis was collapsed and contained smaller accumulations of
      lymphocytes. The pars lymphoepithelialis was almost totally devoid of lymphocytes
      and it was composed of an empty network of epithelial cells. Interfollicular
      epithelium, follicle-associated epithelium, basement-membrane-associated
      epithelium and bursal epithelial cytoreticulum were not changed. The thymus also
      displayed substantial structural changes, whereby the thymic medulla was strongly
      reduced in size.

PMID- 11841360
TI  - Pharmacogenetics in clinical dermatology.
AB  - Systemic therapies are increasingly used in the management of common skin
      diseases, and drug toxicity and relative lack of efficacy remain significant
      problems. In addition, we are unable to predict life-threatening adverse
      reactions such as toxic epidermal necrolysis. Pharmacogenetics, the study of how
      genetic differences influence the variability of individual patient responses to
      drugs, aims to distinguish responders from non-responders and predict those in
      whom toxicity is likely. Successful application of pharmacogenetics should lead
      to rationalized drug therapy. Recent advances in molecular genetic techniques
      such as high-throughput genotyping and microarrays have the potential to provide
      a practicable and economical approach to future pharmacogenetic testing.
      Pharmacogenetics will change not only the way drugs are selected but will also
      impact on clinical trial design and the costs of healthcare delivery.

PMID- 11841361
TI  - U.K. guidelines for the management of cutaneous melanoma.
AB  - These guidelines for management of cutaneous melanoma present evidence-based
      guidance for treatment, with identification of the strength of evidence available
      at the time of preparation of the guidelines, and a brief overview of
      epidemiological aspects, diagnosis and investigation. To reflect the
      collaborative process for the U.K., they are subject to dual publication in the
      British Journal of Dermatology and the British Journal of Plastic Surgery.

PMID- 11841362
TI  - Multiprofessional guidelines for the management of the patient with primary
      cutaneous squamous cell carcinoma.
AB  - These guidelines for management of primary cutaneous squamous cell carcinoma
      present evidence-based guidance for treatment, with identification of the
      strength of evidence available at the time of preparation of the guidelines, and
      a brief overview of epidemiological aspects, diagnosis and investigation.

PMID- 11841363
TI  - Epidermal-dermal interactions regulate gelatinase activity in Apligraf, a tissue
      engineered human skin equivalent.
AB  - BACKGROUND: Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs
      (TIMPs) have important functions during skin development, repair and maintenance.
      MMP-2 and MMP-9 (gelatinase A and gelatinase B) are involved in regulating
      keratinocyte migration. OBJECTIVES: To analyse whether Apligraf, a bilayered
      tissue-engineered human skin equivalent (HSE), produces gelatinases and TIMPs and
      whether or not epidermal-dermal interactions regulate MMP activity. METHODS: The
      tissue distribution of MMP-2, MMP-9, TIMP-1, TIMP-2 and fibronectin was analysed
      by immunohistochemistry. Secreted MMP activity was quantified by a fluorimetric
      assay and gelatin zymography was used to monitor gelatinases in tissue culture
      supernatants. RESULTS: Apligraf expressed MMP-2 and MMP-9 and contained
      immunohistochemically detectable amounts of TIMP-1 and TIMP-2. The gelatinases
      were predominantly produced in the epidermis, whereas immunostaining of TIMP-1
      and TIMP-2 was largely confined to the dermal component of the HSE. Fibronectin
      was expressed only in the dermis. Gelatin zymography demonstrated that intact
      Apligraf produced both MMP-2 and MMP-9, the latter predominantly in its latent
      form. Separation of the dermis from the epidermis resulted in an enhanced
      production and activation of MMP-9 by the epidermal layer, and secretion of
      latent and active MMP-2 by the dermal layer. Moreover, the incubation media of
      the separated epidermis demonstrated significantly stronger MMP activity than did
      intact Apligraf or its dermal component. CONCLUSIONS: These observations provide
      evidence that epidermal-dermal interactions suppress epidermal gelatinase
      activity. In addition, coexpression of TIMPs and fibronectin in the Apligraf
      dermis suggests that the product has the potential to counteract the imbalance
      between matrix production and degradation in chronic wounds and thus may support
      wound re-epithelialization.

PMID- 11841364
TI  - Tumour necrosis factor-alpha-induced migration of human Langerhans cells: the
      influence of ageing.
AB  - BACKGROUND: Langerhans cells (LCs) play essential roles in the initiation and
      regulation of cutaneous immune responses mediated through their successful
      migration from the epidermis to draining lymph nodes while carrying antigen.
      Tumour necrosis factor (TNF)-alpha, a keratinocyte-derived cytokine, has recently
      been shown to play an important role in the mobilization of LCs from human
      epidermis. Although it is known that with age the immune system changes, the
      influence of increasing age on the function of human LCs has not been defined
      clearly. OBJECTIVES: To examine the influence of age on the ability of TNF-alpha
      to induce LC migration. METHODS: Ten elderly (six men, four women; mean age 76
      years, range 72-79) and 10 young (six men, four women; mean age 23 years, range
      18-35) volunteers received intradermal injections of 200 U of human recombinant
      TNF-alpha diluted in sterile saline, and control injections of sterile saline
      alone, at each of two paired sites identified on photoprotected buttock skin. Two
      hours later, paired injection sites were excised by punch biopsy. One set of
      paired biopsies was processed for assessment of the frequency and morphology of
      epidermal LCs, following preparation of epidermal sheets and immunofluorescence
      staining for the LC marker CD1a. The remaining paired biopsies were processed in
      formalin and the inflammatory response to TNF-alpha was assessed by standard
      histological examination. RESULTS: Mean +/- SEM baseline values for LC frequency
      within epidermal sheets were significantly different between young (1156.3 +/-
      38.5 cells mm(-2)) and elderly subjects (835.7 +/- 48.2 cells mm(-2); P < 0.01).
      Intradermal injections of 200 U of TNF-alpha caused a significant reduction in
      the frequency of LCs in both elderly and young subjects (P < 0.01). However, the
      extent of TNF-alpha-induced LC migration was substantially different between the
      two groups, with a mean 9% reduction in LC frequency in elderly volunteers
      compared with a mean 23% decrease in young subjects. Exposure to TNF-alpha was
      associated with a perivascular polymorphonuclear infiltrate at 2 h in all young
      subjects; in contrast, only 50% of the elderly individuals showed evidence of
      such a response. CONCLUSIONS: There are significant differences between young and
      old skin with respect to both resting LC numbers and their response to TNF-alpha.
      These age-related changes in LC frequency and function may contribute to the
      altered cutaneous immune function observed in the elderly.

PMID- 11841365
TI  - Procyanidin B-2, extracted from apples, promotes hair growth: a laboratory study.
AB  - BACKGROUND: We have previously reported that several selective protein kinase C
      (PKC) inhibitors, including procyanidin B-2, promote hair epithelial cell growth
      and stimulate anagen induction. OBJECTIVES: We discuss the hypothesis that the
      hair-growing activity of procyanidin B-2 is related to its downregulation or
      inhibition of translocation of PKC isozymes in hair epithelial cells. METHODS: We
      examined the effect of procyanidin B-2 on the expression of PKC isozymes in
      cultured murine hair epithelial cells as well as PKC isozyme localization in
      murine dorsal skin at different stages in the hair cycle. RESULTS: We observed
      that procyanidin B-2 reduces the expression of PKC-alpha, -betaI, -betaII and 
      eta in cultured murine hair epithelial cells and also inhibits the translocation
      of these isozymes to the particulate fraction of hair epithelial cells. Our
      immunohistochemical analyses demonstrated that PKC-alpha, -betaI, -betaII and 
      eta are specifically expressed in the outer root sheaths of both anagen and
      telogen hair follicles. The hair matrix at the anagen stage showed no positive
      staining for these PKC isozymes. Moderate to intense staining for PKC-betaI and 
      betaII in the epidermis and hair follicles was observed in a telogen-specific
      manner; however, expression of PKC-alpha and -eta during the telogen stage was
      not conspicuous. Go 6976, an inhibitor of calcium-dependent (conventional) PKC,
      proved to promote hair epithelial cell growth. CONCLUSIONS: These results suggest
      that PKC isozymes, especially PKC-betaI and -betaII, play an important role in
      hair cycle progression and that the hair-growing mechanisms of procyanidin B-2
      are at least partially related to its downregulation of PKC isozymes or its
      inhibition of translocation of PKC isozymes to the particulate fraction of hair
      epithelial cells.

PMID- 11841366
TI  - Genotyping for HLA-A, B and C alleles in Japanese patients with pemphigus:
      prevalence of Asian alleles of the HLA-B15 family.
AB  - BACKGROUND: There have been only limited reports on major histocompatibility
      complex class I antigens in pemphigus. OBJECTIVES: To characterize HLA-A, B and C
      class I alleles by genotyping in Japanese patients with pemphigus, and to analyse
      the possible association of class I alleles with disease susceptibility within a
      relatively homogeneous ethnic population. METHODS: Alleles of HLA-A, B and C, and
      DRB1 and DQB1 loci were fully determined in 51 Japanese patients with pemphigus.
      RESULTS: Asian alleles of the HLA-B15 family, including the allele B*1507, which
      was significantly increased in comparison with normal controls, were prevalent in
      patients with pemphigus vulgaris (PV). The prevalence of B*15 alleles in patients
      with PV was not due to linkage disequilibrium with HLA-DR4 or DR14 alleles, which
      have been shown to confer strong susceptibility to PV across racial barriers. In
      contrast to the unique distribution of the HLA-B alleles, HLA-A and C alleles
      were unremarkable in patients with PV when compared with normal control subjects.
      CONCLUSIONS: These results suggest that there may be differences in the ethnic
      concentrations of different HLA-B alleles in patients with PV.

PMID- 11841367
TI  - Extracorporeal photopheresis in cutaneous T-cell lymphoma and graft-versus-host
      disease induces both immediate and progressive apoptotic processes.
AB  - BACKGROUND: Extracorporeal photopheresis (ECP) therapy is used in the treatment
      of many T-cell-mediated conditions including cutaneous T-cell lymphoma and graft
      versus-host disease and involves the reinfusion of a patient's own white cells
      following exposure to 8-methoxypsoralen and ultraviolet A. ECP has been
      demonstrated to induce significant levels of apoptosis in treated lymphocytes.
      Previous work has highlighted the importance of mitochondria and the caspase
      cascade in the regulation and execution of apoptosis and, more recently, a
      functional role for CD10 has been proposed for apoptotic lymphoid cells in vivo.
      OBJECTIVES: To determine the effect of ECP on phosphatidylserine (PS) exposure,
      mitochondrial function, caspase activation and CD10 expression of treated
      lymphocytes. METHODS: Lymphocytes were tested pre-ECP and at several stages post
      ECP for changes to PS, mitochondrial transmembrane potential (DeltaPsim),
      activated caspases and CD10 expression. RESULTS: Early apoptosis induced a
      disruption in DeltaPsim, while caspase activation was not observed until 24 h
      post-ECP. CD10 expression was very weak and "late" in the apoptotic process.
      CONCLUSIONS: The early induction of apoptosis by ECP involves mitochondrial
      dysfunction, while later apoptosis is associated with the activation of caspases.
      CD10 expression was very weak and "late", preceded by a strong PS exposure. These
      apoptotic processes, in vivo, would induce the immediate and progressive
      phagocytosis of the majority of ECP-treated lymphocytes within 48 h.

PMID- 11841368
TI  - Expression of a sonic hedgehog signal transducer, hedgehog-interacting protein,
      by human basal cell carcinoma.
AB  - BACKGROUND: Aberrant activation of the hedgehog pathway has been identified in
      various human tumours, including familial and sporadic basal cell carcinomas
      (BCCs). It has been postulated that binding of sonic hedgehog protein (SHH) to
      its receptor, patched protein (PTC), releases the inhibitory effect of PTC
      against smoothened protein (SMO), another protein of the SHH signalling pathway.
      The positive SMO signalling is not downregulated in BCCs because of the
      mutational inactivation of PTC. Recently, hedgehog-interacting protein (HIP) was
      found to bind to SHH directly and attenuate SHH signalling like PTC, while its
      expression was induced by SHH signals. OBJECTIVES: To examine the expression
      patterns of HIP, SHH and PTC gene mRNA by human BCCs, in comparison with those by
      normal human skin and various skin tumours. METHODS: We performed quantitative
      reverse transcriptase-polymerase chain reaction analyses with a series of samples
      from BCCs, other skin tumours and normal skin. RESULTS: We found that the mRNA
      expression of both HIP and PTC genes was enhanced in all samples of BCCs, whereas
      none of the other skin tumours tested exhibited an increased level of such mRNAs
      as compared with normal skin. The transcription of the SHH gene, however, was at
      a baseline level in most BCCs. CONCLUSIONS: These results indicate that both HIP
      and PTC gene expression are specifically involved in the development of BCCs, and
      that the production of HIP is linked with the expression of the PTC gene but not
      the SHH gene.

PMID- 11841369
TI  - Expression of the 67-kDa elastin receptor in perforating skin disorders.
AB  - BACKGROUND: Perforating skin dermatoses include elastosis perforans serpiginosa
      (EPS), reactive perforating collagenosis, Kyrle's disease and perforating
      folliculitis. In addition to these four diseases, an acquired form of perforating
      dermatosis associated with diabetes mellitus and/or chronic renal failure has
      been reported for which the term acquired perforating dermatosis (APD) was
      proposed. The molecular mechanism of transepidermal elimination of dermal
      components in perforating skin dermatoses remains unclear. We recently
      demonstrated that the 67-kDa elastin receptor can be detected in the epidermis
      eliminating altered elastic fibres in EPS, suggesting that the elastin
      keratinocyte interaction may play a role in transepidermal elimination in EPS.
      OBJECTIVES: To determine whether the 67-kDa elastin receptor is involved in other
      perforating diseases. METHODS: Paraffin-embedded skin specimens from new cases of
      EPS (n = 2), APD (n = 15) and perforating granuloma annulare (PGA; n = 2) were
      studied immunohistochemically using a specific antibody to the 67-kDa elastin
      receptor. In one case of EPS, two different sites from a single lesion, a central
      atrophic area and a peripheral keratotic area, were studied. RESULTS: Expression
      of the elastin receptor was detected in the epidermis surrounding the elastic
      materials in both cases of EPS. The elastin receptor was not detected in the
      central inactive area, whereas it was expressed strongly in the peripheral
      keratotic active area. The elastin receptor was also detected in three of 15
      cases of APD in which a few elastic fibres were found in the eliminated dermal
      materials. In one case of APD, the elastin receptor was not detected in spite of
      the presence of a few elastic fibres in the eliminated materials. The elastin
      receptor was not detected in either case of PGA. CONCLUSIONS: Expression of the
      elastin receptor in EPS was seen in both cases studied and was dependent on the
      stage of the lesion. Expression of the elastin receptor in APD appeared to be
      related to the amount of elastic fibres in the eliminated materials. Thus,
      expression of the elastin receptor in perforating skin disorders may depend on
      the stage of the lesion and/or the content of elastic fibres in the dermal
      materials being eliminated.

PMID- 11841370
TI  - Aberrant expression of complement regulatory proteins, membrane cofactor protein
      and decay accelerating factor, in the involved epidermis of patients with
      vitiligo.
AB  - BACKGROUND: Vitiligo is a pigmentary disorder of the skin characterized by the
      complete absence of melanocytes from the lesion. Complement-activating
      antimelanocyte antibodies have been implicated in vitiligo pathogenesis. As
      membrane regulators of complement activation, membrane cofactor protein, decay
      accelerating factor and CD59 protect cells from elimination by autologous
      complement, their absence or downregulation on melanocytes may be associated with
      autoantibody and complement-mediated melanocyte destruction in vitiligo.
      OBJECTIVES: We studied the expression of these regulatory proteins in non
      lesional, perilesional and lesional vitiligo skin compared with those of control
      specimens. METHODS: We used immunohistochemistry to study the expression of the
      regulatory proteins, and flow cytometric analysis of cultured melanocytes to
      investigate possible constitutive changes in the expression levels of these
      molecules. We also investigated whether melanocytes can influence keratinocyte
      susceptibility to autologous complement by regulating keratinocytic decay
      accelerating factor and membrane cofactor protein expression levels. RESULTS:
      Immunohistochemical data showed that expression of membrane cofactor protein and
      decay accelerating factor in whole epidermis was lower in lesional and
      perilesional skin in comparison with non-lesional skin. The reduced in situ
      expression appeared to be specific to vitiligo. However, coculture experiments
      indicated that melanocytes do not influence keratinocyte susceptibility to
      autologous complement. Further, flow cytometric analysis of cultured melanocytes
      convincingly demonstrated that non-lesional vitiligo and control melanocytes have
      comparable decay accelerating factor, membrane cofactor protein and CD59
      expression levels. CONCLUSIONS: It is therefore concluded that there is no
      constitutive melanocyte defect per se that could be related to the in vivo
      expression of these molecules in vitiligo. Nevertheless, the present data suggest
      that both keratinocytes and melanocytes in the involved vitiliginous whole
      epidermis express lower levels of decay accelerating factor and membrane cofactor
      protein compared with controls that could render them more vulnerable to
      autologous complement attack.

PMID- 11841371
TI  - Widespread insecticide resistance in head lice to the over-the-counter
      pediculocides in England, and the emergence of carbaryl resistance.
AB  - BACKGROUND: Increasing resistance to insecticides used for the control of head
      lice infestation has been documented over the last decade. Treatment failure and
      tolerance to insecticides have been validated in a number of studies undertaken
      in several U.K. centres. OBJECTIVES: To establish the extent of insecticide
      resistance in head lice and acetylcholinesterase activity in the presence of
      carbaryl in head lice. METHODS: Head lice were collected from school children in
      four centres across England (Exmouth, Loughborough, Leeds and South Shields), and
      tested in their response to the insecticides permethrin, phenothrin, malathion
      and carbaryl. Data were compared with information collected in Bristol and Bath
      in 1998 and with susceptible body lice. The activity of louse
      acetylcholinesterase was measured with and without carbaryl in head lice
      collected in Bristol, Leeds, Loughborough and in body lice. The efficacy of a 1%
      carbaryl lotion was compared in children in Bristol and Leeds. RESULTS: Compared
      with body lice, head lice from all six centres were significantly different in
      their response (P < 0.0001) to permethrin, phenothrin and malathion after 2-h
      exposure tests. There were significant differences in louse acetylcholinesterase
      activity in body lice, and head lice collected in Loughborough and Bristol in the
      presence or absence of carbaryl (P < 0.001), indicating enzyme inhibition.
      However, the difference for lice from Leeds was not significant (P = 0.363)
      suggesting that the enzyme was resistant to carbaryl. Eighty-nine per cent of
      children treated in Leeds with carbaryl were cured compared with 100% in Bristol.
      CONCLUSIONS: The data suggest head lice resistance is present in many parts of
      England to over-the-counter products containing synthetic insecticides
      (permethrin, phenothrin and malathion). They further suggest that resistance is
      starting to develop to carbaryl in head lice in Leeds and that extensive use of
      this product would lead to significant resistance.

PMID- 11841372
TI  - Topical treatment of actinic keratoses with 3.0% diclofenac in 2.5% hyaluronan
      gel.
AB  - BACKGROUND: Actinic keratoses (AKs) are premalignant skin lesions, which, if left
      untreated, can develop into squamous cell carcinoma. Current treatments for AKs
      are destructive and are often associated with significant adverse events. The
      development of an effective and well-tolerated topical treatment for AK is
      desirable. OBJECTIVES: To evaluate the efficacy and safety of 3.0% diclofenac in
      2.5% hyaluronan gel as a treatment for AK. METHODS: This was a multicentre,
      double-blind, placebo-controlled study in which 195 patients with at least five
      AKs in up to three designated treatment blocks were randomized to four treatment
      groups. Patients randomized into the active treatment groups A30 (n = 49) and A60
      (n = 48) received topical treatment with 3.0% diclofenac in 2.5% hyaluronan gel
      0.5 g twice daily for 30 or 60 days, respectively. Patients in the placebo
      (vehicle gel) groups V30 (n = 49) and V60 (n = 49) received topical treatment
      with 2.5% hyaluronan gel 0.5 g twice daily for 30 or 60 days, respectively.
      Treatment efficacy was assessed by target and cumulative lesion number scores
      (TLNS and CLNS, respectively) and lesion total thickness score (TTS).
      Investigator and patient global improvement indices (IGII and PGII) were also
      used to rate overall improvement. RESULTS: Compared with placebo, significantly
      more patients given active treatment for 60 days had TLNS = 0 (33% vs. 10%, P <
      0.05; an improvement of 64% compared with 34% with placebo), CLNS = 0 (31% vs.
      8%, P < 0.05; an improvement of 54% compared with 23% with placebo) and TTS = 0
      (25% vs. 6%, P < 0.05; an improvement of 59% compared with 31% with placebo). The
      IGII and PGII scores were also significantly better when active treatment was
      compared with placebo (P < 0.05). Both treatments were generally well tolerated
      and the incidence of the most common adverse events was similar between groups.
      CONCLUSIONS: Treatment with 3.0% diclofenac in 2.5% hyaluronan gel was effective
      when used for 60 days and was well tolerated in patients with AK.

PMID- 11841373
TI  - The prevalence and descriptive epidemiology of atopic dermatitis in Singapore
      school children.
AB  - BACKGROUND: Atopic dermatitis is a common disease that appears to be increasing
      in frequency during recent decades. Most of the studies are based on the Western
      population, and there are few data in the Asian population. OBJECTIVES: To
      determine the prevalence and descriptive epidemiology of atopic dermatitis among
      school children in the general community in Singapore. METHODS: This is a
      questionnaire study of 12 323 students done over a 1-year period, comprising 7
      year olds (4605), 12 year olds (3940) and 16 year olds (3778) from 19 primary and
      17 secondary schools randomly selected in Singapore. All children had a complete
      cutaneous examination. The diagnosis of atopic dermatitis was based on the U.K.
      Working Party diagnostic criteria. The questionnaire was translated into Chinese
      and both the English and Chinese versions were issued simultaneously to the
      students. RESULTS: The 1-year period prevalence of atopic dermatitis was 20.8%.
      Atopic dermatitis was present in 22.7% of 7 year olds, 17.9% of 12 year olds and
      21.5% of 16 year olds. The overall sex ratio was equal. There were slightly more
      boys with atopic dermatitis among the younger children (6 and 12 year olds, 1.18
      : 1 and 1.19 : 1, respectively) but more girls were affected (1.57 : 1) among the
      16 year olds. Atopic dermatitis was more common among the Chinese (21.6%) and
      Malays (19.8%) compared with the Indians (16%) and other races (14%). The onset
      of the disease occurred before the age of 10 years in 49.5% of the 16 year olds.
      "Pure" atopic dermatitis without concomitant respiratory allergies was noted in
      788 respondents (30.7%); 1775 (69.3%) suffered from a "mixed" type, with 34.3%
      having allergic rhinitis, 9.5% having asthma and 25.5% having both asthma and
      allergic rhinitis. More boys had atopic dermatitis and concomitant respiratory
      allergies whereas more girls were affected with "pure" atopic dermatitis alone
      (1.4 : 1). At least one first-degree family member with atopy was noted in 1435
      children (56%): atopic dermatitis (70%), asthma (62%) and allergic rhinitis
      (68%). Among siblings with one parent with atopic dermatitis, 37% had either a
      father or a mother with atopic dermatitis. Common aggravating factors reported
      included exercise, heat and sweating, grass intolerance, thick clothing and
      stress. Pityriasis alba was noted in 25% of the study population, keratosis
      pilaris in 13% and ichthyosis vulgaris in 8%. Most respondents had mild to
      moderate atopic dermatitis that could be controlled with a fairly simple regimen
      of moisturizers, topical steroids, antihistamines and antibiotics. CONCLUSIONS:
      The high prevalence of atopic dermatitis in Singapore is similar to that observed
      in developed countries, suggesting that environmental factors may be important in
      determining the expression of the disease.

PMID- 11841374
TI  - Genetic epidemiology of Darier's disease: a population study in the west of
      Scotland.
AB  - BACKGROUND: Darier's disease has a world-wide distribution, but estimates of
      prevalence have varied. The discovery that the disease is due to mutations in
      ATP2A2 provides the opportunity to study the genetic epidemiology of the disease
      in localized populations. OBJECTIVES: To survey the prevalence of Darier's
      disease in the west of Scotland and look for founder effects in this population.
      METHODS: We ascertained cases of Darier's disease in the west of Scotland and
      used genealogy and mutational analysis to seek common ancestry. RESULTS: Seventy
      eight current cases were identified, giving a prevalence of approximately 1 : 30
      000. While 63 cases gave a history of Darier's disease in previous generations,
      conventional genealogy identified only two pairs of two family groups with common
      ancestry within the last 180 years. Eleven patients (14%; three of whom had in
      total four affected children) had probable de novo mutations. Causative mutations
      in ATP2A2 have been identified in 11 of 15 pedigrees screened for mutation, but
      no two share the same mutation. CONCLUSIONS: High estimates of prevalence are
      likely to be due to intensive ascertainment, rather than founder effects.
      Darier's disease is likely to be more common than has been recognized in other
      populations.

PMID- 11841375
TI  - The natural history of chronic urticaria and angioedema in patients visiting a
      tertiary referral centre.
AB  - BACKGROUND: Data on the natural history and prognostic variables of chronic
      urticaria and its subtypes are scarce. METHOD: In order to inform our patients
      better about their prognosis we conducted an historical cohort study of patients
      who visited a tertiary referral centre at a university hospital between 1968 and
      1990. Of 950 patients who were seen in our clinic we could trace 544 patients by
      using telephone directories, general practitioner records and population
      registers. These patients were sent a questionnaire. RESULTS: The response to the
      questionnaire was 68.4% (372 patients). Patients with severe disease and longer
      lasting disease at the time of the first visit proved to have a worse prognosis
      than patients with milder disease. The proportion cleared after 5 and 10 years
      was 29% and 44%, respectively. Dermographism showed the best prognosis and cold
      urticaria the worst. Patients with idiopathic urticaria without angioedema and
      the patients with angioedema did not differ significantly in prognosis.
      CONCLUSIONS: Although in this retrospective study patients with severe disease
      may have been more inclined to respond, we may conclude that the study results
      indicate a very refractory course of chronic urticaria in patients visiting a
      specialized dermatological unit. The study is not comparable with studies in
      patients visiting a general practitioner or a dermatology unit in a general
      hospital, but highlights the chronicity of the disease in this subgroup of
      patients with severe urticaria.

PMID- 11841376
TI  - Type IV hypersensitivity reactions to natural rubber latex: results of a
      multicentre study.
AB  - BACKGROUND: Positive patch test reactions to natural rubber latex (NRL) have been
      interpreted as allergic or irritant by different groups. Additives to the NRL
      test solution have also caused positive reactions in previous studies.
      OBJECTIVES: Five centres of the British Contact Dermatitis Group conducted a
      prospective study on the prevalence of type IV hypersensitivity to NRL, using
      ammonia-preserved NRL solution for testing. PATIENTS AND METHODS: A total of 2738
      consecutive patients were patch tested. Where clinically indicated, specific IgE
      was measured or a prick test done. RESULTS: Twenty-seven patients (1%) had a
      positive patch test reaction to NRL, which was considered to be allergic and of
      current relevance in 19 (70%) patients. Fourteen of these also had a positive
      prick test or specific IgE. Thirteen patients (48%) were male, 19 (70%) atopic
      and 13 (48%) had eczema on their hands. CONCLUSIONS: We conclude that delayed
      type hypersensitivity to NRL is a problem for a proportion of patients with
      eczema, particularly on their hands, and that patch testing with ammonia
      preserved NRL can be recommended to identify these patients. Patients with a
      positive patch test should be investigated for contact urticaria to NRL.

PMID- 11841378
TI  - Lack of an association between granuloma annulare and type 2 diabetes mellitus.
AB  - BACKGROUND: Conflicting reports have been published regarding whether a
      relationship exists between granuloma annulare (GA) and diabetes mellitus (DM).
      OBJECTIVES: To evaluate the prevalence of DM in patients with GA using a case
      control design. METHODS: The incidence of DM was determined in 126 patients with
      GA. Fifty of the 126 patients with GA were further compared with an age-, sex-
      and race-matched population of psoriasis patients seen during a similar time
      period in the same clinical setting. RESULTS: Eleven (9%) of 126 GA patients
      suffered from type 2 DM. In the matched comparison of 50 patients, 11 (22%) GA
      patients and 10 (20%) psoriasis patients suffered from type 2 DM. CONCLUSIONS:
      This case-control study failed to reveal any statistically significant
      correlation between GA and type 2 DM.

PMID- 11841377
TI  - Etanercept for severe psoriasis and psoriatic arthritis: observations on
      combination therapy.
AB  - BACKGROUND: The antitumour necrosis factor (TNF) activity of etanercept has been
      utilized to generate an important and novel treatment for rheumatoid arthritis.
      TNF has also been implicated in the pathogenesis of psoriasis. OBJECTIVES: To
      determine whether blockade of TNF activity by etanercept may provide an
      additional treatment option for patients with psoriasis. METHODS: In an
      uncontrolled trial, etanercept was added to the treatment regimen in six patients
      with severe recalcitrant psoriasis (three also with psoriatic arthritis)
      partially resistant to other ongoing systemic agents. RESULTS: In each case, the
      disease activity showed marked improvement on addition of etanercept therapy. No
      added toxicity was found with etanercept. CONCLUSIONS: Etanercept appears to be a
      promising immunomodulatory agent that can be used in combination therapy for the
      treatment of psoriasis, and a prospective controlled trial may be warranted.

PMID- 11841379
TI  - Subungual perineurioma: a peculiar location.
AB  - We report the first case of subungual perineurioma presenting as clubbing of one
      finger, an unusual clinical feature. Histological study showed a myxoid tumour
      but with, unexpectedly, a diffuse expression of CD34. Differential diagnoses
      between perineurioma and myxoid soft tissue tumours expressing CD34 are
      discussed.

PMID- 11841380
TI  - Sclerosing perineuriomas affecting bilateral hands.
AB  - Sclerosing perineurioma is a rare, recently described variant of perineurioma
      that tends to affect the fingers and palms of adolescents or young adults. The
      process typically presents as a painless, well-circumscribed, unencapsulated
      nodule involving subcutis or reticular dermis. To our knowledge, all of the
      previously reported sclerosing perineuriomas were solitary. Hence, we report a 16
      year-old boy, without stigmata of neurofibromatosis, who developed one sclerosing
      perineurioma in the right palm and another on the left index finger.
      Microscopically, tumours at both sites revealed small epithelioid and plump
      spindle cells with trabecular, whorled, or Indian file growth pattern enmeshed
      within extensively hyalinizing stroma. Immunohistochemically, the tumour cells
      showed strong reactivity for EMA but negative staining for S-100 and
      neurofilament. Ultrastructually, the tumour cells in both lesions exhibited
      features of perineurial cells, including discontinuous external basal lamina,
      occasional pinocytotic vesicles, and encirclement of abundant collagen fibrils by
      the interdigitating cytoplasmic processes. This case confirms the fact that
      sclerosing perineurioma is not always solitary.

PMID- 11841381
TI  - Primary lymphoedema associated with xanthomatosis, vaginal lymphorrhoea and
      intestinal lymphangiectasia.
AB  - Primary lymphoedema associated with chylous reflux is a very rare clinical
      entity. We report a 3-year-old girl with unilateral lymphoedema, xanthomatosis
      and vaginal lymphorrhoea. Biopsy also revealed intestinal lymphangiectasia. This
      paper also presents a brief review of the literature and draws attention to the
      significance of the xanthomatous eruption in the diagnosis of a chylous reflux.

PMID- 11841382
TI  - Vegetative pyoderma gangrenosum in chronic renal failure.
AB  - We report the case of a 58-year-old woman with painful recurrent erythematous
      lesions on both legs of 6 months' duration. The patient had been treated with
      haemodialysis for chronic renal failure for the previous 10 years. Physical
      examination revealed pea-sized erythematous nodules with sinus formation and
      discharge of bloody pus, which yielded neither bacterial nor fungal cells in
      culture. These lesions healed leaving cribriform scars, after bed rest, topical
      disinfection and systemic and in some areas intralesional corticosteroids. Cases
      of pyoderma gangrenosum are usually classified as one of four clinical variants:
      ulcerative, pustular, bullous and vegetative. Our case might correspond to a
      vegetative form in view of the development of sinuses, neutrophilic abscesses and
      palisading granuloma, even though no ulceration was observed.

PMID- 11841383
TI  - Cutaneous large B-cell lymphoma of the leg masquerading as a chronic venous
      ulcer.
AB  - We report on a 74-year-old female patient with a primary cutaneous CD20+, diffuse
      large cell B-cell lymphoma of the lower leg resembling a chronic non-healing leg
      ulcer. There was no evidence of systemic involvement on computed tomography (CT)
      scans of the chest, abdomen and pelvis; a slightly enlarged lymph node in the
      right groin showed dermatopathic lymphadenopathy on histology and
      immunohistochemistry. Involvement of the bone marrow and peripheral blood was
      ruled out by punch biopsy and fluorescent activated cell sorter (FACS) analysis
      of the blood, respectively. Therapeutic anti-CD20 monoclonal antibody rituximab
      was given at 375 mg m(-2) i.v. once weekly for 7 weeks, without adverse effects,
      resulting in a minor improvement in the centre of the ulcerated tumour.
      Unfortunately, the response was not maintained, and after 7 weeks of treatment
      the patient started to develop new tumour lesions at the border of the ulcer.
      Local radiotherapy was started and combined photon and electron beam irradiation
      induced complete remission of the B-cell lymphoma.

PMID- 11841384
TI  - A case of lymphoblastoid natural killer (NK)-cell lymphoma: association with the
      NK-cell receptor complex CD94/NKG2 and TP53 intragenic deletion.
AB  - The clinical, histological, phenotypic and genotypic features of a lymphoblastoid
      natural killer (NK)-cell lymphoma presenting in the skin in a young caucasian
      woman are described. The disease behaved aggressively, but long-lasting remission
      was obtained by combination chemotherapy followed by autologous bone marrow
      transplantation. The blastoid cells were positive for terminal deoxynucleotidyl
      transferase, CD34, CD56 and CD4. Furthermore, the NK-cell receptor complex
      CD94/NKG2 was strongly expressed, as shown by examination with reverse
      transcription-polymerase chain reaction. The T-cell receptor (TCR)-gamma genes
      were in germline, and with the exception of CD4 all T-cell antigens were
      negative, including CD3, TCR-beta, TCR-delta, TIA-1, granzyme B and perforin.
      Epstein-Barr virus was negative, and no expression was seen of myeloid cell
      associated markers. Molecular analysis showed no abnormalities of the CDKN2A
      (p16), CDKN2B (p15) or TNFRSF6 (Fas) genes. By contrast, a 34-bp deletion in exon
      7 of the TP53 (p53) gene was detected. It is suggested that lymphoblastoid NK
      cell lymphoma, which is a rare but distinctive disease, originates from NK cell
      precursors and may be associated with and possibly caused by alterations in the
      TP53 gene. Experience is too limited to warrant therapeutic suggestions. However,
      stem cell transplantation may be a useful option in younger patients.

PMID- 11841385
TI  - Melanocytic agminated naevus on the sole.

PMID- 11841386
TI  - Onychopapilloma is not a distinct clinicopathological entity.

PMID- 11841387
TI  - Absence of human herpesvirus 8/Kaposi's sarcoma-associated herpesvirus in a case
      of benign lymphangioendothelioma associated with periosteal haemangioma.

PMID- 11841389
TI  - 'Wet wrap' dressings for eczema: an effective treatment but not to be misused.

PMID- 11841390
TI  - Two cases of bullous eosinophilic cellulitis.

PMID- 11841391
TI  - Vitamin E for dapsone-induced headache.

PMID- 11841392
TI  - Blood and blisters: porphyria cutanea tarda in myelodysplastic syndrome.

PMID- 11841393
TI  - Polyclonal hypergammaglobulinaemia with hyperviscosity syndrome.

PMID- 11841394
TI  - The Langerhans cell histiocytosis X files revealed.

PMID- 11841395
TI  - Chronic neutrophilic leukaemia: a distinct clinical entity?

PMID- 11841396
TI  - Signalling scaffolds and adaptors in T-cell immunity.

PMID- 11841397
TI  - Haematopoietic growth factors in children with neutropenia.

PMID- 11841399
TI  - Generation of cytokine-induced killer cells from leukaemic samples with in vitro
      cytotoxicity against autologous and allogeneic leukaemic blasts.
AB  - Cytokine-induced killer (CIK) cells are CD3(+)CD56(+) non-major
      histocompatibility complex (MHC)-restricted immune effector cells. The present
      report demonstrates that it was possible to expand CIK cells obtained at
      diagnosis from patients with acute leukaemia. The percentage of CD3(+)CD56(+) CIK
      cells generated following culture ranged between 7.6% and 65% (median of 35.3%)
      and these cells were able to kill the human natural killer target K562 cells.
      Although the same effector cells were able to lyse autologous acute myeloid
      leukaemia (AML) target cells, they were not able to lyse autologous acute
      lymphoblastic leukaemia target cells. Pre-absorption of the CIK effector cells by
      K562 cells did not completely abrogate the cytotoxicity of CIK cells against
      autologous blasts in 9 out of 12 samples tested. Moreover, it was observed that
      the cytotoxicity generated by the CIK effector cells against allogeneic leukaemic
      blasts was similar to that against autologous blasts. The present study suggests
      the potential application of CIK cells in the immunotherapy of AML, either in
      minimal disease state, as donor lymphocyte infusion in relapse post allogeneic
      transplant, or in cases of chemotherapy refractory leukaemia.

PMID- 11841398
TI  - Cellular signalling pathways: new targets in leukaemia therapy.

PMID- 11841400
TI  - The TEL-AML1 real-time quantitative polymerase chain reaction (PCR) might replace
      the antigen receptor-based genomic PCR in clinical minimal residual disease
      studies in children with acute lymphoblastic leukaemia.
AB  - Prospective studies in children with B-precursor acute lymphoblastic leukaemia
      (ALL) have shown that polymerase chain reaction (PCR)-based detection of minimal
      residual disease (MRD) using immunoglobin (Ig) and T-cell receptor (TCR) gene
      rearrangements as targets can be used to identify patients with a high relapse
      risk. The disadvantage of this approach is that for each patient preferably two
      different targets have to be identified. The t(12;21)(p13;q22) with the TEL-AML1
      fusion gene is present in approximately 25% of children with B-precursor ALL. In
      these patients, sensitive reverse transcription (RT)-PCR analysis of the TEL-AML1
      fusion transcript might be a more simple and less laborious alternative approach.
      However, it is unknown how stable the mRNA is and whether the number of
      transcripts per leukaemic cell remains constant during follow-up. We investigated
      whether the MRD results obtained using RT-PCR of TEL-AML1 transcripts correlated
      with the clinically validated genomic PCR for Ig and TCR gene rearrangements.
      Therefore, we used real-time quantitative (RQ)-PCR analysis for both types of
      targets and assessed the MRD levels in 36 follow-up bone marrow samples (obtained
      during the first 1.5 years after diagnosis) from 13 patients with B-precursor
      ALL. In 34/36 bone marrow samples the Ig/TCR RQ-PCR and TEL-AML1 RQ-PCR revealed
      equal levels of MRD and these results had a strong correlation (P < 0.0001, R2 =
      0.84). Therefore, we conclude that the TEL-AML1 RQ-PCR can, in principle, replace
      Ig/TCR RQ-PCR in B-precursor ALL with t(12;21).

PMID- 11841401
TI  - Matrix metalloproteinase-9 and vascular endothelial growth factor: a possible
      link in adult T-cell leukaemia cell invasion.
AB  - Plasma from a total of 57 patients with adult T-cell leukaemia (ATL) (acute ATL,
      39 patients; lymphoma ATL, one patient; chronic ATL, 15 patients; smouldering
      ATL, two patients) and 20 healthy controls was analysed for the presence of type
      IV gelatinase activity with clinical features. A significant elevation of plasma
      matrix metalloproteinase-9 (MMP-9) was observed in some ATL patients,
      particularly in the patients with malignant cell infiltration. MMP-9 was found to
      be secreted into the conditioned medium from all ATL cell lines examined.
      Moreover, the corresponding mRNA was detectable both in all ATL cell lines
      examined and in the majority of primary acute ATL cells, indicating that ATL
      cells are capable of synthesizing and secreting MMP-9. We previously demonstrated
      that a high incidence of ATL cell infiltration was closely related to a high
      plasma level of vascular endothelial growth factor (VEGF) produced by ATL cells
      themselves. This present study showed that the presence of increased plasma MMP-9
      was closely associated with elevated plasma VEGF in ATL patients. Furthermore, we
      showed that both increased plasma MMP-9 and VEGF were significantly related to
      high ATL cell infiltration. All these findings strongly suggest that MMP-9 and
      VEGF act co-operatively in the process of ATL cell invasion.

PMID- 11841402
TI  - Efficacy of granulocyte colony-stimulating factor in the treatment of acute
      myelogenous leukaemia: a multicentre randomized study.
AB  - To investigate the efficacy and safety of granulocyte colony-stimulating factor
      (G-CSF) in patients with acute myelogenous leukaemia, a multicentre randomized
      study was performed. From October 1993 to September 1996, 270 patients with newly
      diagnosed acute myelogenous leukaemia were randomized to G-CSF or control groups
      after remission induction therapy. The G-CSF group received G-CSF (Filgrastim)
      from 48 h after the completing chemotherapy until the absolute neutrophil count
      exceeded 1.5 x 10(9)/l. The control group did not receive G-CSF unless severe
      infection occurred. There were 245 evaluable patients (120 and 125 in the G-CSF
      and control groups respectively). The complete remission rate was similar in the
      G-CSF and control groups (80.8% versus 76.8%), as was the 5-year probability of
      disease-free survival (34.5% versus 33.6%) and overall survival (42.7% versus
      35.6%). Neutrophil recovery was significantly faster in the G-CSF group than in
      the control group (12 d versus 18 d, P = 0.0001). The median duration of febrile
      neutropenia was significantly shorter in the G-CSF group than in the control
      group (3 d versus 4 d, P = 0.0001). In conclusion, prophylactic administration of
      G-CSF after remission induction therapy for acute myelogenous leukaemia is safe
      and useful even in patients without infection on completing chemotherapy.

PMID- 11841403
TI  - Primary effusion lymphomas exhibit complex and recurrent cytogenetic
      abnormalities.
AB  - Cytogenetic findings in a few primary effusion lymphoma (PEL) cell lines have
      been reported, but only three complete karyotypes of primary specimens from
      patients with this neoplasm have been published. In this study, cytogenetic
      analysis was performed on 11 effusion specimens from 10 patients with PEL. We
      corroborate data obtained from the cell line studies that trisomy 7, trisomy 12
      and aberrations in the proximal long arm of chromosome 1 (1q) are recurring
      cytogenetic aberrations in PEL and also identify breakpoints at 3q23, 7p22, 7q22,
      10q24, 12q24, 13q22, 14q24, 14q32, 15p11.2 and Xq22 as well as +8, +15, +19, +X
      and -Y as recurring chromosome abnormalities. The identification of recurring
      cytogenetic aberrations may lead to delineation of the genetic events in PEL.

PMID- 11841404
TI  - T-cell analysis in identical twins reveals an impaired anti-follicular lymphoma
      immune response in the patient but not in the healthy twin.
AB  - In lymphomas an innate defect in the T-cell repertoire could account for the
      impaired tumour-specific immune response; alternatively, the tumour itself could
      exert an inhibitory effect on the immune system. To address this issue we
      analysed the T-cell responses against follicular lymphoma (FL) in identical twins
      as it can be postulated that their overall T-cell repertoire is identical. While
      differences between the T-cell response of the patient and the healthy twin would
      point to a tumour-induced T-cell unresponsiveness, impaired responses in both
      would point to a defective T-cell repertoire. We demonstrated an impaired tumour
      specific proliferation (P = 0.035 and P = 0.013) and cytokine release (P = 0.004
      and P = 0.0008) of both peripheral blood and tumour-derived T-cells,
      respectively, in the FL patient compared with the T-cell response of the healthy
      twin. Moreover, only syngeneic primed T cells were able to directly lyse
      unmodified FL cells of the patient. These data support previous findings in
      murine lymphomas and suggest that inhibitory mechanisms during tumour growth,
      rather than a defective T-cell repertoire, are responsible for the insufficient T
      cell response in lymphoma.

PMID- 11841406
TI  - Immunochemical studies of antigenic lymphoma-associated proteins.
AB  - We have previously reported that plasma from patients with anaplastic lymphoma
      kinase (ALK)-positive lymphoma contains antibodies against the oncogenic kinase
      NPM-ALK protein characteristic of this disease. We investigated whether this
      reactivity represents a phenomenon unique to ALK-positive lymphoma by screening
      plasma from patients with follicular lymphoma for antibodies to BCL-2 protein.
      Eight out of 10 samples showed such reactivity (and in six cases gave specific
      staining of BCL-2-transfected cells). As these findings suggest a new biochemical
      approach to the identification of oncogenic proteins in lymphoma, we investigated
      whether antibodies present in patients with ALK-positive lymphoma can precipitate
      NPM-ALK in quantities which should be sufficient for further analysis. We found
      that plasma samples from all10 patients studied immunoprecipitated NPM-ALK
      asaprotein visible in silver-stained sodium dodecyl sulphatepolyacrylamide gels.
      Finally we demonstrated that NPM-ALK could be visualized more clearly if it were
      immunoprecipitated from extracts of cells in which newly synthesized proteins had
      been labelled with 35S and then identified by autoradiography. These results
      suggest a strategy for using patients' autoantibodies to screen for antibodies to
      other tumour-associated proteins.

PMID- 11841405
TI  - Establishment and characterization of a Kaposi's sarcoma-associated herpesvirus-
      and Epstein-Barr virus-negative malignant lymphoma cell line (OHK) with primary
      effusion lymphoma immunophenotype.
AB  - A novel cell line, designated OHK, was established from ascites of a 59-year-old
      Japanese woman with diffuse large B-cell lymphoma showing a peculiar serosal
      tropism, as seen in primary effusion lymphomas (PEL). OHK exhibited a large
      pleomorphic morphology with irregular nuclei and distinct nucleoli, and included
      immunoblastic and Reed-Sternberg-like giant cells. On ultrastructural
      examination, rich intermediate filaments, and well-developed Golgi apparati and
      rough endoplasmic reticulum, were seen. Immunophenotypically, OHK lacked T and B
      cell-associated antigens, and had CD10, CD30, CD33 and CD138 antigens. Although
      OHK cells did not express immunoglobulin (Ig) protein, Southern blot analysis
      demonstrated clonal rearrangements of Ig heavy and light chain genes. These
      observations suggest that OHK cells are derived from preterminally differentiated
      B cells, and that they have features of PEL. Kaposi's sarcoma-associated
      herpesvirus and Epstein-Barr virus were not detected. OHK displayed hyperploid
      karyotypes with multiple structural abnormalities, and produced some cytokines
      such as macrophage-colony-stimulating factor (M-CSF), granulocyte-CSF,
      interleukin 6 and transforming growth factor beta 1. In particular, vascular
      endothelial growth factor (VEGF), whose stimulation of vascular permeability is
      thought to be critical to the pathogenesis of PEL, was also produced in large
      quantities. These results indicate that OHK may be a useful tool for the
      investigation of PEL.

PMID- 11841407
TI  - CD38 expression and secondary 17p deletion are important prognostic factors in
      chronic lymphocytic leukaemia.
AB  - CD38 expression and chromosomal abnormalities are novel prognostic factors in
      chronic lymphocytic leukaemia (CLL). However, their value remains undetermined.
      CD38 was evaluated in 123 patients and chromosomal aberrations in 111 cases with
      fluorescence in situ hybridization (FISH). CD38 expression was found in 27% of
      the cases. In addition, seven out of 32 CD38- patients became CD38+ during
      evolution of the disease. Chromosomal abnormalities included isolated 13q
      deletion (40%), 12q trisomy (14%), 11q deletion (without 17p deletion) (14%) and
      17p deletion (7%). CD38 expression was significantly associated with Binet stages
      B and C, atypical morphology and 11q deletion. On univariate analysis of survival
      estimates, advanced Binet stages, CD38+ phenotype, atypical morphology and 11q or
      17p deletions were associated with shorter event-free survival (EFS), treatment
      free interval (TFI) and overall survival (OS). Multivariate analysis identified
      both Binet stages and CD38 as independent prognostic factors with regard to EFS
      and TFI. However, CD38 appeared as an independent factor for OS when restricted
      to Binet stage A. Chromosomal aberrations were re-evaluated during evolution in
      31 cases. The 17p deletion was the most frequent new chromosomal abnormality
      (35%) and significantly associated with death (64%). In conclusion, CD38
      expression and secondary 17p deletion are important poor prognostic indicators,
      especially in Binet stage A CLL.

PMID- 11841408
TI  - Evolution of myelodysplastic syndrome and acute myelogenous leukaemia in children
      with hepatitis-associated aplastic anaemia.
AB  - In hepatitis-associated aplastic anaemia (HAA), an immune-mediated mechanism is
      solely responsible for the development of pancytopenia. We retrospectively
      analysed the clinical outcome of 61 children with HAA, diagnosed between 1988 and
      1996. Of 61 patients, 41 did not receive bone marrow transplantation (BMT) and
      their survival rate at 7 years was 61.4 +/- 9.3%(+/- SE). Five of these 41
      patients developed myelodysplastic syndrome (MDS) or acute myelogenous leukaemia
      (AML) 7-57 months after the diagnosis of HAA. The incidence of MDS/AML in severe
      HAA patients who did not receive BMT (n = 30, 27.0 +/- 10.8%) appeared to be
      similar to that of severe idiopathic AA patients (n = 155, 14.7 +/- 3.7%) treated
      in the same period.

PMID- 11841409
TI  - Chronic myeloid leukaemia with marked thrombocytosis in a patient with
      thalassaemia major: complete haematological remission under the combination of
      hydroxyurea and anagrelide.
AB  - The co-existence of thalassaemia major and chronic myeloid leukaemia (CML) is a
      very rare event. We report a 32-year-old man with thalassaemia major whose
      progressively increasing leukocytosis and thrombocytosis led to the diagnosis of
      CML confirmed by the characteristic t(9;22)(q34;q11) chromosomal translocation
      and the bcr-abl (b3a2) DNA fusion. The patient was treated with hydroxyurea and
      anagrelide. This combination resulted in the satisfactory control of both the
      white blood cell and platelet counts, which has continued over the past 14 months
      with no major side-effects, albeit with no molecular response. The administration
      of hydroxyurea was also associated with a significant HbF increase.

PMID- 11841410
TI  - High expression of MCL1 gene related to vascular endothelial growth factor is
      associated with poor outcome in non-Hodgkin's lymphoma.
AB  - We evaluated the level of MCL1 gene expression using quantitative reverse
      transcription polymerase chain reaction in lymph nodes of patients with non
      Hodgkin lymphoma (NHL). MCL1 expression in patients in complete remission (CR)
      was significantly lower than in patients with progressive disease (PD, P =
      0.0043). The disease-free survival rate was significantly higher in patients with
      MCL1 levels below the median level (P = 0.007). We also found that the level of
      expression of MCL1 mRNA was related to that of vascular endothelial growth factor
      mRNA in NHL lymph nodes. Our data suggest that the MCL1 expression level could be
      considered a prognostic factor in NHL.

PMID- 11841411
TI  - Effects of combinations of therapeutic agents on the proliferation of progenitor
      cells in chronic myeloid leukaemia.
AB  - Combination of STI571, a tyrosine kinase inhibitor, with other drugs may be
      beneficial in the treatment of chronic myeloid leukaemia (CML). We measured the
      effects of STI571, AG490, farnesyltransferase inhibitor (FTI), interferon alpha
      (IFN-alpha), cytosine arabinoside (Ara-C) and all-trans retinoic acid (ATRA),
      singly and in combination, on clonogenic leukaemic cell proliferation. STI571,
      IFN-alpha and ATRA each reduced proliferation by 50-60%; AG490, FTI and Ara-C had
      less effect. Comparing the observed and expected (i.e. additive) effects of drug
      combinations showed STI571 + FTI, STI571 + AG490 and IFN-alpha + ATRA were
      additive; STI571 + IFN-alpha, IFN-alpha + Ara-C and STI571 + AG490 + FTI were
      less than additive. Thus, STI571 + FTI, STI571 + AG490 and IFN-alpha + ATRA may
      be better combination therapies for CML than STI571 + IFN-alpha, IFN-alpha + Ara
      C or STI571 + AG490 + FTI.

PMID- 11841412
TI  - Lamivudine for the treatment of hepatitis B virus reactivation following
      chemotherapy for non-Hodgkin's lymphoma.
AB  - Chemotherapy for non-Hodgkin's lymphoma (NHL) patients with chronic hepatitis B
      virus (HBV) infection may be accompanied by severe hepatitis. Of 86 consecutive
      NHL patients, 11 (12.8%) exhibited a positive serum HBsAg. Six of these patients
      (54.5%) developed acute exacerbation of chronic HBV infection following
      chemotherapy and received lamivudine. Five of the six patients demonstrated a
      clinical improvement, one patient died from fulminant hepatic failure owing to
      delayed lamivudine therapy and poor compliance. These data suggest that HBsAg
      screening is necessary before commencing chemotherapy for NHL patients in a
      hyperendemic area and that lamivudine is effective in treating hepatitis B
      reactivation during chemotherapy.

PMID- 11841413
TI  - t(7;11)(p15;p15) Chronic myeloid leukaemia developed into blastic transformation
      showing a novel NUP98/HOXA11 fusion.
AB  - We encountered a patient with Philadelphia-negative chronic myeloid leukaemia,
      with t(7;11)(p15;p15), in whom acute leukaemia phase (acute myeloid leukaemia-M2
      morphology) developed within a short period. We detected a novel gene fusion
      between NUP98 and HOXA11 both in the chronic phase and in the acute leukaemia
      phase in this case. Although it is well known that a fusion of NUP98-HOXA9 in
      myeloid malignancies is created by the t(7;11)(p15;p15), this case suggests the
      possibility that HOXA11 might be another partner gene for NUP98 in
      t(7;11)(p15;p15) leukaemia.

PMID- 11841414
TI  - Interleukin 8 and venous thrombosis: evidence for a role of inflammation in
      thrombosis.
AB  - Elevated plasma levels of interleukin 8 (IL-8) were previously shown to be
      associated with recurrent venous thrombosis. To assess the risk of venous
      thrombosis, IL-8 plasma concentrations were measured in patients and control
      subjects of the Leiden Thrombophilia Study (LETS). This population based case
      control study included 474 patients with a first deep-vein thrombosis and 474 age
      and sex-matched controls. The risk of venous thrombosis for subjects with
      elevated IL-8 levels (above 90th percentile of controls) compared with subjects
      with IL-8 levels below the 90th percentile was increased 1.8-fold (95%CI 1.2
      2.8). Adjusted for age and sex, the odds ratio was 1.9 (95%CI 1.3-2.8). IL-8
      concentrations were weakly correlated with age, male sex, and concentrations of C
      reactive protein, factor VIII coagulation activity and homocysteine, but
      adjustment for these factors did not substantially affect the association between
      IL-8 and venous thrombosis. Our results suggest that IL-8 is a risk factor for
      venous thrombosis.

PMID- 11841415
TI  - Mechanisms responsible for the failure of protamine to inactivate low-molecular
      weight heparin.
AB  - Protamine is unable to completely reverse the anticoagulant effect of the low
      molecular-weight heparins (LMWH), a fact of clinical importance given the rapid
      increase in use of LMWH in clinical practice. This investigation sought to
      determine the mechanism by which LMWH were able to resist protamine-mediated
      inactivation. Affinity fractionation of LMWH by passage through a protamine
      column, with subsequent determination of molecular mass and sulphate charge
      density, demonstrated that the protamine-resistant fraction in LMWH is an ultra
      low-molecular-weight fraction with low sulphate charge density. This group of
      molecules was not found in unfractionated heparin, even when species of similar
      molecular mass were compared. We then determined that different commercially
      available LMWH varied in their ability to be neutralized by protamine, and that
      this variability correlated with the total sulphate content of the LMWH. We
      conclude that reduced sulphate charge, not molecular mass, is the principle
      reason that protamine is unable to fully inactivate LMWH. Furthermore, different
      LMWH vary in their ability to be neutralized by protamine, suggesting that
      product-specific recommendations for neutralization might be developed.

PMID- 11841416
TI  - Use of the collagen-binding assay for von Willebrand factor in the analysis of
      type 2M von Willebrand disease: a comparison with the ristocetin cofactor assay.
AB  - This study compares the utility of two functional assays for von Willebrand
      factor (VWF), the ristocetin cofactor assay (VWF:RCo) and the collagen-binding
      assay (VWF:CBA). We analysed a group of 32 patients with type 2 von Willebrand
      disease (VWD) (25 patients with type 2M, six with type 2A and one with type 2B)
      and 22 normal control subjects. VWF:RCo/VWF antigen (VWF:Ag) ratios and
      VWF:CBA/VWF:Ag ratios were compared between the patient and control groups. In
      the six patients with type 2A VWD, both VWF:RCo/VWF:Ag ratios and VWF:CBA/VWF:Ag
      ratios were discordant (< or = 0.7). In the 25 type 2M VWD patients, the
      VWF:CBA/VWF:Ag ratios were concordant (> 0.7), but the VWF:RCo/VWF:CBA ratios
      were discordant (< or = 0.7) (P = 0.001) compared with control subjects. Thus,
      VWF:RCo/VWF:Ag ratios were discordant in both type 2M and 2A VWD patient groups
      indicating a functional abnormality. However, VWF:CBA/VWF:Ag ratios were
      discordant in the type 2A VWD group but not in the type 2M VWD group. Our study
      showed that VWF:CBA is sensitive to functional variants associated with the loss
      of high-molecular-weight multimers, i.e. type 2A and 2B in VWD, but the assay was
      unable to discriminate defective platelet-binding VWD variants with normal
      multimeric patterns such as type 2M VWD. It was concluded that the VWF:CBA assay
      should be used in association with rather than as a replacement for the VWF:RCo
      assay.

PMID- 11841417
TI  - Prior treatment with alpha interferon does not adversely affect the outcome of
      allogeneic transplantation for chronic myeloid leukaemia.
AB  - The timing of transplantation in chronic myeloid leukaemia is still debated and
      previous treatment with interferon (IFN) alpha has been reported to be
      deleterious. We have analysed the outcome of 438 allogeneic transplants performed
      between 1984 and 1995 and reported to the Societe Francaise de Greffe de Moelle
      (SFGM) registry. One hundred and two patients (group I) received IFN for more
      than 6 weeks (median = 9 months) before transplant. Their outcome was compared
      with 336 other patients (group II) not pretreated with IFN. There were no
      significant differences between the groups for engraftment and chronic graft
      versus-host disease (GVHD) incidence. However, other significant differences
      included the incidence of acute GVHD > or = 2 at 3 months which was higher in
      group I (65 +/- 10%) than in group II (38 +/- 5%; P = 0.01). Moreover, disease
      free survival (DFS) and overall survival (OS) at 5 years were significantly
      shorter for group I than for group II (33 +/- 10% vs. 41 +/- 6%; P = 0.005)(95%
      CI) and (41 +/- 10% vs. 55 +/- 6%; P = 0.002)(95% CI) respectively. After
      adjustment for patient and transplant covariables in a multivariate analysis,
      prior IFN was not found to adversely affect transplant outcome.

PMID- 11841418
TI  - Negative selection of peripheral blood stem cells to support a tandem autologous
      transplantation programme in multiple myeloma.
AB  - We recently described a two-step negative selection procedure whereby peripheral
      blood stem cells (PBSCs) were efficiently purged of contaminating neoplastic
      cells by a combination of monoclonal antibodies. Here, we report 60 newly
      diagnosed multiple myeloma (MM) patients treated with a double transplant
      programme and randomized to receive either unmanipulated or in vitro purged
      PBSCs. We demonstrated that this technique is feasible and safe without
      significant loss of either CD34+ or CD3+ cells. Haematological engraftment and
      immunological reconstitution were rapid without treatment-related mortality.
      Using polymerase chain reaction (PCR), we compared the level of minimal residual
      disease (MRD) in PBSC before and after in vitro purging and in vivo after
      transplant. A median of one tumour cell per 10(2) normal cells (range 10(1)
      10(5)) was seen in the unmanipulated aphereses with a 3-4 log reduction after
      manipulation in vitro. However, despite this tumour debulking, all patients
      remained PCR positive in vivo. At 3 years, the estimated event-free survival was
      40% in the control arm and 72% in the experimental arm (P = 0.05), whereas the
      estimated overall survival was 83% in both arms. This suggests that autologous
      transplantation using efficiently purged PBSCs can be performed safely, but
      confirms the need for innovative protocols for MRD eradication in vivo.

PMID- 11841419
TI  - Predicting long-term (> or = 5 years) event-free survival in multiple myeloma
      patients following planned tandem autotransplants.
AB  - Although outcome in multiple myeloma (MM) patients has improved significantly
      with the introduction of autotransplants (AT), the curability of this approach
      remained to be demonstrated. Therefore, we analysed outcome and prognostic
      factors using a logistic regression model in 515 consecutive newly diagnosed and
      previously treated patients intended to receive melphalan-based tandem
      transplants with follow up of > or = 5 years. One quarter of patients had event
      free survivals (EFS) > or = 5 years with no further relapses seen after 7 years
      (46 patients on plateau). On multivariate analysis, factors associated with EFS >
      or = 5 years were absence of chromosome 11 and 13 abnormalities (odds ratio:
      6.1), < or = 12 months of preceding standard-dose therapy (SDT) (OR: 2.6) and
      beta-2 microglobulin (B2M) level < or = 2.5 mg/l at time of first AT (OR: 1.7).
      Patients with only favourable variables (25%) had a 7-year EFS in excess of 35%,
      compared with 15% and 10%, respectively, with one (43%) or two unfavourable
      variables (27%), and 0% for 5% of patients with three unfavourable variables (P <
      0.0001). Using a 1-year landmark analysis to allow for guaranteed time and
      thereby excluding early treatment failures, attaining a complete remission (CR)
      had no significant effect on long-term survival. Our data are consistent with
      cure in MM patients with a CR duration . or = 7 years and re-establishment of a
      monoclonal gammopathy of undetermined significance (MGUS) phase in those with
      persistent evidence of disease post transplantation, but without disease
      progression > or = 7 years.

PMID- 11841420
TI  - In vitro expansion of cord blood does not prevent engraftment of severe combined
      immunodeficient repopulating cells.
AB  - This study aimed to assess the potential of human cord blood (CB) cells to
      engraft in the xenogenic non-obese diabetic/severe combined immunodeficient
      (NOD/SCID) mouse model after in vitro expansion culture. We also studied the
      quality of human haemopoiesis arising from the transplantation of fresh or
      expanded cells in this model. Cord blood CD34(+) cells were cultured for 3, 7 or
      10 d with stem cell factor, Flt3, thrombopoietin, interleukin 3 (IL-3), IL-6 and
      granulocyte colony-stimulating factor, all at 10 ng/ml in serum-replete
      conditions. Transplantation of mice with fresh CB containing 3 x 10(4) CD34(+)
      cells and 1-2 SCID repopulating cells (SRC) resulted in a median of 7.4% (0.4%
      76.8%) human engraftment. When mice received the expanded product of 1-2 SRC, the
      ability to repopulate NOD/SCID mice was maintained even after 10 d of in vitro
      culture. Serial dilution of the expanded cells suggested that in vitro expansion
      had increased SRC numbers two- to fourfold. Expanded SRC produced long-term
      culture-initiating cells, clonogenic cells and CD34(+) cells in the same
      proportions as fresh cells after successful engraftment. Therefore, expanded SRC
      were able to differentiate in the same way as fresh SRC. There was a trend
      towards lower levels of engraftment when d 7 cultured cells were transplanted
      (median engraftment 0.8%, range 0.0-24.0%) compared with 1-2 fresh SRC. Our data
      suggest that this is owing to reduced proliferation of cultured cells in vivo. By
      utilizing limiting numbers of CB SRC, we confirmed that the engraftment potential
      of SRC in the NOD/SCID model was preserved after in vitro expansion. Furthermore,
      dilution experiments strongly suggest two- to fourfold expansion of SRC in vitro.
      These studies are relevant for developing clinical stem cell expansion
      strategies.

PMID- 11841422
TI  - Blastic natural killer cell leukaemia/lymphoma.

PMID- 11841421
TI  - A sequence of immuno-chemotherapy with Rituximab, mobilization of in vivo purged
      stem cells, high-dose chemotherapy and autotransplant is an effective and non
      toxic treatment for advanced follicular and mantle cell lymphoma.
AB  - Options for relapsed/refractory indolent lymphoma include chemotherapy,
      immunotherapy and high-dose therapy with autologous support. The best combination
      of these approaches, however, is not defined. We treated 10 patients with
      relapsed/refractory follicular (n = 7) or mantle cell lymphoma (n = 3) using
      chemotherapy, immunotherapy, high-dose therapy and autotransplant in a sequence
      of four phases, each designed to play a specific role in tumour eradication.
      After the debulking with VACOP-B (doxorubicin, cyclophosphamide, etoposide,
      vincristine, prednisone, bleomycin) (phase 1), 9/10 patients responded but none
      achieved a molecular response. After the immuno-chemotherapy phase, which
      combined Rituximab with vincristine and cyclophosphamide, seven patients were in
      complete response (CR) and three in good partial response (PR), and all those
      with a molecular marker of disease showed a disappearance of the signal from
      marrow and blood. Phase 3, which coupled high-dose cytarabine with Rituximab, was
      effective in mobilizing an adequate number of progenitor cells that were
      polymerase chain reaction negative in all informative cases. Phase 4 consisted of
      high-dose therapy with autologous support followed by two doses of Rituximab.
      Autograft was performed in nine patients. The haematopoietic recovery was as
      expected. This sequence of chemotherapy, immuno-chemotherapy, stem cell
      mobilization with in vivo purging and autotransplant, organized in four blocks of
      treatment, was simple to administer and devoid of toxic effects. It permits rapid
      attainment of clinical and molecular response and enables the harvest of lymphoma
      free peripheral blood progenitor cells even in heavily pretreated patients with
      relapsed or refractory disease.

PMID- 11841423
TI  - Demonstration of left iliofemoral deep vein thrombosis by magnetic resonance
      direct thrombus imaging.

PMID- 11841424
TI  - The optimal management of polycythaemia vera.

PMID- 11841425
TI  - Medication errors: causes, prevention and reduction.

PMID- 11841426
TI  - ETV6 (TEL)-AML1 pre-B acute lymphoblastic leukaemia cells are associated with a
      distinct antigen-presenting phenotype.
AB  - The recently recognized translocation t(12;21)(p13;q22), which results in the
      ETV6-AML1 fusion product, is the most common genetic rearrangement found in
      childhood pre-B acute lymphoblastic leukaemia (ALL). It has been associated with
      a more favourable prognosis and a distinct immunophenotype in terms of myeloid
      and B cell-associated antigen expression. Using flow cytometry, we investigated
      whether the unique ETV6-AML1 phenotype extended to molecules associated with
      antigen presentation by analysing 50 diagnostic bone marrow samples from
      paediatric pre-B ALL patients. Reverse transcription polymerase chain reaction
      for the ETV6-AML1 fusion transcript was positive in 14 patients. ETV6-AML1
      positive samples were characterized by a significantly higher expression of the
      co-stimulatory molecule CD40 (P < 0.0001), as well as a significantly higher
      class II HLA-DR mean channel fluorescence (P = 0.001). In contrast, CD86
      expression was significantly lower on fusion-positive samples (P = 0.010) while
      there was no difference in expression of CD80 or major histocompatibility complex
      class I between ETV6-AML1-positive and -negative samples. This is the first
      observation in acute leukaemia that the distinct immunophenotype associated with
      specific translocations includes the expression of molecules associated with
      antigen presentation. In the case of ETV6-AML1 pre-B ALL, this characteristic
      immunophenotype may have implications for the immunogenicity of the leukaemic
      cells.

PMID- 11841427
TI  - Differential expression of CD56 and CD44 in the evolution of extramedullary
      myeloma.
AB  - We report on the different expression of CD56 and CD44 in plasma cells (PCs)
      simultaneously collected from bone marrow, extramedullary locations and
      peripheral blood in seven patients with multiple myeloma. Extramedullary PCs
      showed absence of CD56. In the bone marrow, however, subsets with varying CD56
      expression were found in five out of seven patients, with one subset
      corresponding to that of extramedullar PCs. This differs from the de novo
      downregulation of CD56 in PC leukaemia, and suggests different mechanisms of
      spread of myeloma cells. CD44 expression was generally upregulated on
      extramedullary PCs. In three of the patients we investigated the clonal origin of
      extramedullary myeloma cells by sequencing the variable portion of the heavy
      chain immunoglobulin gene in phenotypically defined PCs isolated from different
      locations. In each patient we found malignant PCs with different homing behaviour
      originating from a common precursor cell.

PMID- 11841428
TI  - Myeloma interacts with the bone marrow microenvironment to induce
      osteoclastogenesis and is dependent on osteoclast activity.
AB  - Myeloma tumour growth, except in the most advanced stages of the disease, is
      restricted to the bone marrow. We used the severe combined immunodeficient-human
      (SCID-hu) host system, in which primary human myeloma cells grow in, disseminate
      to and interact with a human microenvironment, to study the interactions between
      myeloma cells and cells in the bone marrow microenvironment. We used inhibitors
      of osteoclast activity to determine the role of osteoclasts and their products in
      supporting myeloma cell growth. Treatment of myelomatous SCID-hu hosts with an
      inhibitor of osteoclast activity (pamidronate or zoledronate) or with a specific
      inhibitor of the receptor activator of NF-kappaB ligand (RANKL) halted myeloma
      induced bone resorption, when present, and resulted in inhibition of myeloma cell
      growth and survival. In contrast, myeloma cells from patients with extramedullary
      disease had a different growth pattern in the SCID-hu hosts and were not
      inhibited by these interventions, indicating that, while still dependent on a
      human microenvironment, these cells no longer required the bone marrow
      microenvironment for survival. This study demonstrates the dependence of myeloma
      cells on osteoclast activity and their products, and highlights the importance of
      the myeloma-osteoclast-myeloma loop for sustaining the disease process. Breaking
      this loop may help control myeloma.

PMID- 11841429
TI  - Identification of novel regions of amplification and deletion within mantle cell
      lymphoma DNA by comparative genomic hybridization.
AB  - We have carried out comparative genomic hybridization (CGH) analysis on archival
      biopsy material from a series of 30 UK mantle cell lymphomas. The most frequent
      aberrations were gains of 3q (21 cases), 6p (19 cases), 7q (8 cases), 12p (8
      cases), 12q (9 cases) and 17q11q21 (8 cases), and losses of 1p13p32 (10 cases),
      5p13p15.3 (9 cases), 6q14q27 (11 cases), 8p (7 cases), 11q13q23 (8 cases) and 13q
      (18 cases). Nineteen cases (63%) had a common region of amplification at 3q28q29,
      which was highly amplified in three cases, suggesting the presence of a mantle
      cell lymphoma (MCL)-related oncogene in this region. There was a minimal common
      region of deletion at 6q25q26 in nine cases (30%). No MCL-specific locus has
      previously been identified on chromosome 6 and this region may contain a tumour
      suppressor gene specifically implicated in the development of this subtype of
      lymphoma. An increased number of chromosome aberrations, gain of Xq and loss of
      17p were all significantly associated with a worse prognosis. A greater
      understanding of the genetics of mantle cell lymphoma may allow the
      identification of prognostic factors which will aid the identification of
      appropriate treatment regimens.

PMID- 11841430
TI  - Expansion of cytotoxic effectors with lytic activity against autologous blasts
      from acute myeloid leukaemia patients in complete haematological remission.
AB  - New therapeutic approaches are needed to improve the cure rates in acute myeloid
      leukaemia (AML). The present study was designed to investigate whether: (1)
      cytotoxic lymphocytes could be expanded from AML patients in complete remission;
      (2) their signal transduction machinery was preserved; (3) these cells were
      capable of producing cytokines involved in the cytolytic process; and (4) these
      cells showed cytotoxic activity against allogeneic and autologous blasts. By co
      culturing blood mononuclear cells with feeder cells, we obtained an average 5.3
      fold increase in the total cell number and a 35-fold increase in natural killer
      (NK) cells. Expression of the zeta chain and of tyrosine kinases of the Src and
      Syk-ZAP families involved in the triggering of NK functions was analysed on
      expanded cells. The results demonstrated a signal transduction apparatus
      preserved and quantitatively similar to that of normal donors. After phorbol
      myristate acetate and ionomicin stimulation, the ability of expanded cells to
      produce interferon gamma and tumour necrosis factor alpha was documented.
      Patients' expanded cells showed a cytotoxic activity against target lines and
      allogeneic blasts which was similar to that of normal donors. Purification
      experiments indicated that the NK cell fraction was responsible for most of the
      lytic effect. More significantly, these cells also exerted a lytic effect against
      autologous blasts that could be further enhanced following incubation with low
      dose interleukin 2. These findings document the possibility of expanding
      cytotoxic effectors with preserved signal transduction machinery and autologous
      killing capacity from AML patients in remission, and suggest a new potential
      immunotherapeutic strategy for the management of early disease recurrence or of
      residual disease.

PMID- 11841432
TI  - Cytoprotective antioxidant activity of serum albumin and autocrine catalase in
      chronic lymphocytic leukaemia.
AB  - Chronic lymphocytic leukaemia (CLL) cells are long lived in vivo but undergo
      spontaneous apoptosis when cultured in vitro. Intriguingly, CLL cells also appear
      to have a specific susceptibility to oxidative stress - a potent inducer of
      apoptosis. Here, we show that serum albumin can function as a cytoprotective
      antioxidant of potential relevance to circulating CLL cells, and that autocrine
      catalase - a hydrogen peroxide-inactivating enzyme that may be released
      extracellularly - can perform a similar role under the crowded conditions that
      prevail at sites of tissue involvement. Albumin lowered oxidative stress in
      cultured CLL cells and inhibited spontaneous and reactive oxidant-induced
      apoptosis. Maximal effects were observed at a concentration of 10 mg/ml -
      fourfold lower than that in plasma and twofold higher than that in standard
      culture medium containing 10% fetal calf serum. Oxidative stress and spontaneous
      apoptosis were also decreased by cell crowding and by conditioned medium (CM)
      from crowded CLL cells, indicating that these processes were subject to autocrine
      regulation. CLL cells were found to express catalase and release enzyme activity
      into the culture medium. Exogenous catalase decreased oxidative stress and
      spontaneous apoptosis, and the anti-apoptotic effect of CM from crowded CLL cells
      was abrogated by the specific catalase inhibitor, 3'-amino-1,2,4-triazole.
      Together, these data strongly implicate autocrine catalase as a cytoprotective
      antioxidant. Oxidative stress in CLL cells was greatly diminished by ruthenium
      red - an inhibitor of mitochondrial reactive oxidant production - and by the
      glutathione (GSH) precursor N-acetylcysteine, suggesting that the GSH peroxidase
      antioxidant system may be compromised by lack of available substrate. Our
      findings highlight the importance of endogenous reactive oxidants in regulating
      CLL-cell apoptosis, and help to explain why CLL cells survive for prolonged
      periods in vivo despite their vulnerability to oxidative stress and spontaneous
      apoptosis when cultured in vitro.

PMID- 11841431
TI  - Safety and early efficacy assessment of liposomal daunorubicin (DaunoXome) in
      adults with refractory or relapsed acute myeloblastic leukaemia: a phase I-II
      study.
AB  - We have conducted a phase I/II trial to determine the maximum tolerated dose,
      early safety and efficacy of single-agent liposomal daunorubicin in relapsed or
      refractory acute myeloid leukaemia (AML). Successive cohorts of six patients
      received escalated doses of 75, 100, 125 or 150 mg/m2 of DaunoXome for three
      consecutive days. Responding patients received a further consolidation cycle of
      DaunoXome at a dose identical to the one inducing complete or partial remission
      at the various dose levels. Twenty-eight patients with a median age of 50.5 years
      were enrolled. A maximum tolerated dose was determined at 150 mg/m2. Twelve
      patients received the second cycle. DaunoXome was well tolerated at all
      administered levels; dose-limiting toxicities included nausea and vomiting,
      mucositis and two episodes of cardiotoxicity resulting in the death of two
      patients. The overall response rate was 46% with a median duration of response of
      180 d and a median duration of survival of 208 d. Ten patients demonstrated a
      complete response following cycle 1, and a further four entered partial response
      with the first cycle (marrow blasts between 5% and 10%). Of these, three attained
      complete response with the second cycle (total complete response 13/28). Our
      results indicate that DaunoXome at a dose of 150 mg/m2 displays acceptable
      toxicity in a 3-d regimen followed by a 3-d consolidation course at 100 mg/m2/d.
      At this dose schedule, interestingly high remission rates were achieved,
      justifying further evaluation of DaunoXome for the treatment of relapsed or
      refractory AML patients.

PMID- 11841433
TI  - Clonally unrelated Hodgkin's disease following autologous stem cell transplant
      for B-cell lymphoma.
AB  - Lymphoproliferative disorders after autologous stem cell transplantation (SCT)
      are rare. We describe two cases of Hodgkin's disease (HD) as a late secondary
      neoplasia following autologous SCT for mantle cell lymphoma and B-cell chronic
      lymphocytic leukaemia respectively. Both HD cases were of mixed cellularity type,
      showed Epstein-Barr virus (EBV) positivity and followed an aggressive course.
      Clonal analysis of rearranged immunoglobulin genes from the primary B-cell
      neoplasm and the secondary HD provided evidence of separate clonal origins of the
      two tumours in both patients, thus excluding secondary transformation of the
      original B-cell clone through EBV as the causative event for development of HD.

PMID- 11841434
TI  - Infliximab chimaeric anti-tumour necrosis factor alpha monoclonal antibody
      treatment for patients with myelodysplastic syndromes.
AB  - Tumour necrosis factor alpha (TNF-alpha) is believed to play a major role in
      apoptotic death of bone marrow cells in myelodysplastic syndromes (MDS). We
      explored the efficacy and safety profile of infliximab chimaeric anti-TNF-alpha
      monoclonal antibody treatment in two MDS patients. They both had low
      /intermediate-risk MDS, isolated anaemia and elevated circulating levels of TNF
      alpha. Infliximab produced no adverse side-effects and resulted in sustained
      erythroid responses, one major and one minor. Laboratory studies indicated a
      remarkable decrease in the percentage of apoptotic stem cells in the bone marrow.
      This preliminary report indicates that infliximab may have an application as MDS
      therapy and warrants further investigation.

PMID- 11841435
TI  - Secondary acute myeloid leukaemia with monosomy 7 in identical adult twins.
AB  - We report the development of secondary acute myeloid leukaemia (AML) with
      monosomy 7 in identical twins, both at the age of 52 years. In the first twin,
      induction therapy resulted in complete remission (CR). At relapse 9 months later
      monosomy 7 was found. The patient died of sepsis 11 months after diagnosis. The
      other twin presented with leucopenia and thrombocytopenia and refractory anaemia
      (RA) was diagnosed. During follow-up, fluorescence in situ hybridization analysis
      demonstrated a monosomy 7 in 11% of the cells. Twenty-eight months following
      diagnosis the patient progressed to RA with excess blasts in transformation and
      induction chemotherapy was initiated without achieving CR. Three months later an
      allogeneic stem cell transplantation from a niece was performed, resulting in CR
      of the secondary AML.

PMID- 11841436
TI  - Spontaneous clinical regression in chronic lymphocytic leukaemia.
AB  - Chronic lymphocytic leukaemia (CLL) is a B-cell disorder, which has a median
      survival of over 10 years from diagnosis for stage A disease. The natural history
      of stage A disease is generally indolent or only slowly progressive. It is less
      well known that CLL may undergo spontaneous regression. We report a series of 10
      such cases (eight stage A and two stage B) followed at our institutions.

PMID- 11841437
TI  - Perforin defects of primary haemophagocytic lymphohistiocytosis in Japan.
AB  - The perforin gene was analysed in 15 Japanese patients with primary
      haemophagocytic lymphohistiocytosis (HLH). Perforin gene defects were found in
      two out of eight patients with familial HLH (FHL), and one out of seven without
      affected siblings. Four novel mutations were identified. Compound heterozygous
      mutations (one FHL and one sporadic HLH) and only one allele mutation (one FHL)
      were defined. Flow cytometry revealed no perforin expression in CD8+ or CD56+
      cells from a surviving patient with a mutation. The frequency of mutation was at
      least 20% of FHL in Japan. Flow cytometry for intracellular perforin may be
      useful for the screening of FHL2.

PMID- 11841439
TI  - Rapid recovery of platelet count following administration of liposome
      encapsulated clodronate in a mouse model of immune thrombocytopenia.
AB  - Immune thrombocytopenic purpura (ITP) is a haematological disorder characterized
      by increased platelet consumption. The destruction of platelets is mediated by
      the reticulo-endothelial system (RES), particularly by splenic and hepatic
      macrophages. Previously, we demonstrated in a mouse model of thrombocytopenia
      that the depletion of these cells by liposome-encapsulated clodronate (LIP-CLOD)
      induces the recovery of the platelet count. We now report that LIP-CLOD is
      capable of reversing the thrombocytopenia with minimal effects on both,
      functional RES integrity and platelet functionality. Our data indicate that
      thrombocytopenic mice treated with low doses of LIP-CLOD/body weight increase the
      platelet count to haemostatically safe values within 18 h of treatment. The
      predictable bleeding time was significantly decreased in these mice, suggesting
      that the circulating platelets have enhanced haemostatic capacity. Platelet
      functionality measured through the ADP-induced fibrinogen-binding assay showed
      normal platelet activation after treatment. Regarding immunological competence,
      mice treated with LIP-CLOD showed similar antibody titres against sheep red blood
      cells. However, antibody-dependent cell-mediated cytotoxicity carried out by
      splenocytes was reduced. All these data demonstrate that LIP-CLOD deserves
      consideration as a potential therapeutic approach in thrombocytopenic states in
      which the rapid increase of platelet count is the primary goal.

PMID- 11841438
TI  - Genotype at the secretor blood group locus is a determinant of plasma von
      Willebrand factor level.
AB  - Previous reports on the effect of Secretor and Lewis blood groups on plasma
      factor VIII-von Willebrand factor (FVIII-VWF) levels have produced conflicting
      findings. To determine whether either or both loci can influence plasma FVIII-VWF
      complex levels, we studied the relationship between Secretor and Lewis genotypes,
      determined definitively using polymerase chain reaction-restriction fragment
      length polymorphism analysis, and plasma FVIII coagulant activity (FVIII:C) and
      VWF antigen (VWF:Ag) levels in 136 healthy volunteers. Overall, significantly
      higher VWF:Ag levels were found in those individuals homozygous for the Se allele
      (genotype SeSe) than in those heterozygous for the Se allele (P < 0.001). To
      minimize any confounding influence of ABO genotype/phenotype, we investigated the
      relationship between Secretor genotype and plasma FVIII-VWF levels within
      individuals of the same ABO blood group genotype. In the subgroup analysis of
      group O1O1 individuals alone, VWF:Ag levels were again significantly higher in
      those individuals with Secretor genotype SeSe than in those either heterozygous
      or homozygous for the se null allele. Among A1O1 subjects, homozygous Secretors
      also had significantly higher VWF:Ag levels. In contrast, we found no
      relationship between Lewis genotype and either VWF:Ag or FVIII:C levels. This
      study is the first based on genotypic rather than serological analysis, and
      resolves the previously confounding effects of the Lewis and Secretor loci on
      plasma FVIII-VWF complex levels.

PMID- 11841440
TI  - Absence of mutations in the HoxA10, HoxA11 and HoxD11 nucleotide coding sequences
      in thrombocytopenia with absent radius syndrome.
AB  - Recent studies have suggested the HoxA10, HoxA11 and HoxD11 homeobox genes as
      candidate loci for the thrombocytopenia with absent radius (TAR) syndrome. For
      example, targeted disruptions of these Hox genes result in abnormal development
      of the mouse radius, while overexpression of HoxA10 stimulates mouse
      megakaryocyte (MK) development in vitro. To examine the expression of Hox genes
      in human MK cells, we utilized reverse transcription polymerase chain reaction
      with degenerate oligonucleotides to study megakaryocytic cell lines (MEG-01,
      DAMI), and primary human MK purified from adult and cord blood. Using this
      approach, 13 out of 40 clones isolated from cell lines, 10 out of 21 from cord
      MK, and 11 out of 21 from adult MK were identified as HoxA10, while HoxA11 and
      HoxD11 sequences were not detected. The normal genomic sequences for the human
      HoxA10, -A11, and -D11 genes were then determined and sequenced in 10 unrelated
      individuals with TAR syndrome. In all patients the derived amino acid sequence
      for the three Hox genes was identical to normal controls. Southern blotting did
      not reveal genomic rearrangements or deletions at these loci, and in two patients
      intact HoxA10 transcripts were detected by amplification in myeloid cells.
      Although these studies cannot completely exclude the possibility that the TAR
      syndrome results from non-coding mutations that affect the level of Hox gene
      expression in megakaryocytes, mutations in the coding sequence of the Hox genes
      known to affect radial development are not a common cause of TAR syndrome.

PMID- 11841442
TI  - Prevalence of IgG antibodies to human parvovirus B19 in haemophilia children
      treated with recombinant factor (F)VIII only or with at least one plasma-derived
      FVIII or FIX concentrate: results from the French haemophilia cohort.
AB  - Human parvovirus B19 (B19) has been transmitted by some brands of virally
      attenuated plasma-derived factor VIII (FVIII) or IX (FIX) concentrates. To
      quantify the differences of human parvovirus B19 risk transmission between
      albumin-stabilized recombinant factor and plasma-derived factor, we studied the
      prevalence of IgG antibodies to B19 (anti-B19) in 193 haemophiliac children
      between 1 and 6-years of age who had previously been treated with albumin
      stabilized recombinant FVIII only (n = 104), and in children previously treated
      with solvent/detergent high-purity non-immunopurified and non-nanofiltered FVIII
      or IX concentrates (n = 89). Association between the prevalence of anti-B19 and
      the treatment group was analysed using multivariate logistic regression. Age,
      severity and type of haemophilia, number of cumulative days of exposure to factor
      VIII or IX, previous history of red blood cells or plasma transfusion were
      considered as potential confounding variables. A higher prevalence of anti-B19
      was found in children previously treated with solvent/detergent high-purity non
      immunopurified and non-nanofiltered FVIII or IX concentrates than in children
      treated with albumin- stabilized recombinant FVIII only (OR: 22.3; CI: 7.9-62.8),
      independently of the other factors studied.

PMID- 11841441
TI  - Coagulation factor XIII polymorphisms and the risk of myocardial infarction and
      ischaemic stroke in young women.
AB  - The inconsistent findings among association studies that have examined the
      relationship between factor XIIIA Val34Leu and thrombosis may be owing to (1)
      population differences in the prevalence of other risk factors that modify the
      association with Val34Leu, or (2) linkage disequilibrium with other functional
      factor XIIIA polymorphisms. We therefore performed genotyping for factor XIIIA
      Val34Leu, Tyr204Phe and Pro564Leu in a population-based study of myocardial
      infarction (MI) and ischaemic stroke among white women <45-years of age and 345
      demographically similar controls, and examined potential interactions with other
      risk factors. The presence of the factor XIIIA Leu34 allele was associated with a
      slight decreased risk of MI [odds ratio (OR) = 0.80] that was most pronounced
      among women with traditional cardiovascular risk factors. Paradoxically, women
      carrying two copies of the Leu34 allele had a nearly fourfold increased risk of
      ischaemic stroke relative to the Val34/Val34 genotype. Heterozygosity for factor
      XIIIA Phe204 was associated with a milder increased risk of ischaemic stroke, and
      analysis of a kindred with congenital dysfibrinogenaemia suggested that co
      inheritance of the factor XIIIA Phe204 allele may increase susceptibility to
      ischaemic stroke. Our results suggest that the factor XIIIA Val34Leu variant may
      be associated with a decreased risk of MI among young women with other risk
      factors. The relationship of factor XIIIA polymorphisms to cerebrovascular
      disease requires further study.

PMID- 11841443
TI  - Axillary vein thrombosis in a healthy donor following platelet apheresis.
AB  - Platelet donation is a common and usually safe procedure accounting for almost
      half of the platelets donated in the UK. We describe a previously healthy female
      donor who developed an axillary vein thrombosis following an apheresis platelet
      donation.

PMID- 11841444
TI  - Fetal haemopoietic cells display enhanced migration across endothelium.
AB  - Fetal haemopoietic cells continually circulate and migrate into tissues, and thus
      may have specialized homing capabilities. In this study we investigated the in
      vitro features of haemopoietic cells in fetal blood and liver which are relevant
      to homing and engraftment. Fetal cells were examined for long-term culture
      initiating cell (LTC-IC) and progenitor content, adhesion molecule expression,
      cell cycle behaviour and transendothelial migratory activity. The LTC-IC content
      of fetal CD34+ cells is similar to that of CD34+ cells from cord and adult
      mobilized blood. In contrast to adult and cord blood CD34+ cells, fetal CD34+
      cells were actively cycling (11.0 +/- 1.7% and 28 +/- 1.1% of fetal blood and
      liver CD34+ cells, respectively, in S+G2M, P < 0.001, compared with cord and
      adult cells). The striking finding was that fetal haemopoietic cells (both LTC
      ICs and committed progenitors) displayed significantly higher levels of migration
      across endothelium (P < 0.05 compared with cord, P < 0.01 compared with adult
      blood and bone marrow CD34+ cells), which were further increased by chemokines
      and growth factors. The superior migratory activity of fetal haemopoietic cells
      may underlie a more efficient homing ability, in keeping with their physiological
      role.

PMID- 11841445
TI  - Expression of the Ly-6A (Sca-1) lacZ transgene in mouse haematopoietic stem cells
      and embryos.
AB  - The Sca-1 surface glycoprotein is used routinely as a marker for haematopoietic
      stem cell enrichment. Two allelic genes, Ly-6A and Ly-6E, encode this marker and
      appear to be differentially regulated in haematopoietic cells and haematopoietic
      stem cells. The Sca-1 protein has been shown to be expressed at a greater
      frequency in these cells from Ly-6A strains of mice. To study the specific
      expression pattern and haematopoietic regulation of the Ly-6A gene, we
      constructed a 14 kb cassette from a genomic Ly-6A fragment, inserted a lacZ
      reporter gene and created transgenic mice. We found that the Ly-6A lacZ transgene
      was expressed in the haematopoietic tissues and predominantly in the T-lymphoid
      lineage. Some expression was also found in the B-lymphoid and myeloid lineages.
      We demonstrated functional haematopoietic stem cell enrichment by sorting for
      beta-galactosidase-expressing cells from the bone marrow. In addition, we found
      an interesting embryonic expression pattern in the AGM region, the site of the
      first haematopoietic stem cell generation. Surprisingly, when compared with data
      from Ly-6E lacZ transgenic mice, our results suggest that the Ly-6A cassette does
      not improve lacZ marker gene expression in haematopoietic cells.

PMID- 11841446
TI  - Very low frequencies of human normal CD34+ haematopoietic progenitor cells
      express the Wilms' tumour gene WT1 at levels similar to those in leukaemia cells.
AB  - The Wilms' tumour gene, WT1, is expressed at high levels in leukaemia cells and
      plays an important role in leukaemogenesis. WT1 is also expressed in human normal
      CD34+ bone marrow (BM) cells at about 100 times lower levels than in leukaemia
      cells. To identify and characterize WT1-expressing cells in CD34+ BM cells, they
      were sorted into single cells and analysed for WT1 expression using two kinds of
      single-cell reverse transcriptase polymerase chain reaction (RT-PCR) methods.
      Using the semiquantitative single-cell polyA-PCR + sequence-specific (SS)-PCR
      method, WT1 expression was detected in four (1.3%) out of 319 CD34+ BM single
      cells. To confirm the above results, a single-cell nested sequence-specific (NSS)
      RT-PCR method that was less quantitative but more sensitive than the polyA-PCR +
      SS-PCR method was also performed, and WT1 expression was detected in 15 (1.1%)
      out of 1315 CD34+ BM single cells. In total, WT1 expression was found in 19
      (1.2%) out of 1634 CD34+ BM single cells. No significant differences in the
      frequencies of WT1-expressing cells were found between CD34+CD38- and CD34+CD38+
      BM single cells. Furthermore, WT1-expressing CD34+ BM single cells expressed WT1
      at levels similar to those in K562 leukaemia single cells. Analysis of lineage
      specific and cell cycle gene expression in WT1-expressing CD34+ BM single cells
      showed that the WT1 gene could be expressed in both uncommitted, dormant
      CD34+CD38- and lineage-committed, proliferating CD34+CD38+ BM cells. Our results
      could indicate that these WT1-expressing CD34+ BM cells were normal counterparts
      of leukaemia cells.

PMID- 11841447
TI  - p53-mediated downregulation of Chk1 abrogates the DNA damage-induced G2M
      checkpoint in K562 cells, resulting in increased apoptosis.
AB  - BCR-ABL confers apoptotic resistance to a range of genotoxic agents, and this
      protection is mediated in part by prolonging the G2 checkpoint. The p53 tumour
      suppressor protein regulates the transcription of regulatory genes involved in
      cell cycle arrest and apoptosis. To investigate the effect of p53 on the BCR-ABL
      mediated G2M checkpoint response, we transiently transfected the BCR-ABL
      positive, p53-negative cell line K562 with wild-type human p53. The p53
      transfected cells showed a decreased ability to arrest in G2 and an increase in
      apoptosis in response to etoposide treatment, relative to the control mock
      transfected cells. p53-transfected and control cells were treated with etoposide
      and trapped at mitosis with nocodazole. The mitotic index of p53-transfected
      cells was higher than that of the control cells, which suggests that p53
      abrogates the G2 checkpoint response to etoposide treatment in K562 cells. We
      found that the expression of the cell cycle checkpoint protein Chk1 was reduced
      in the etoposide-treated p53-transfected cells by 24 h, and this correlated with
      a reduction in the extent of etoposide-induced phosphorylation of CDK1 at
      tyrosine 15 (Y15). We conclude, therefore, that p53 overrides the strong G2
      checkpoint response to etoposide in K562 cells, by directly or indirectly
      downregulating Chk1 expression, which, in turn, contributes to the proapoptotic
      effect of p53.

PMID- 11841448
TI  - Expression of transcription factors Pu.1, Spi-B, Blimp-1, BSAP and oct-2 in
      normal human plasma cells and in multiple myeloma cells.
AB  - Differentiation of B lymphocytes into plasma cells is regulated by the
      interaction of distinct transcription factors (TFs) which activate gene
      expression in a lineage- and stage-specific pattern. Using reverse transcription
      polymerase chain reaction, we studied the expression of five TFs (octamer binding
      factor oct-2, ets family members PU.1 and Spi-B, pax gene family member BSAP, and
      Blimp-1) in (1) human cell lines with a plasma cell phenotype, (2) primary
      malignant plasma cells [obtained from patients with plasma cell leukaemia (PCL)
      and multiple myeloma], and (3) normal human plasma cells generated in vitro or
      isolated from normal bone marrows. The expression pattern was compared with TFs
      expressed by normal CD19+ B lymphocytes and by B cells from chronic lymphocytic
      leukaemia patients. Our results showed that plasma cells expressed a restricted
      set of TFs compared with CD19+ B lymphocytes, with continued expression of Spi-B
      and oct-2, increased Blimp-1 expression, and downregulation of BSAP and PU.1.
      Cells from PCL lost Spi-B and PU.1 expression completely and expressed only oct-2
      and Blimp-1, and thus resembled plasma cell lines. Human plasma cell
      differentiation therefore seems to be positively regulated by Blimp-1; whether
      this TF has any oncogenic potential will have to be analysed in future studies.

PMID- 11841451
TI  - A novel rearrangement of the human fetal globin genes leading to a six gamma
      globin gene haplotype.
AB  - Haematological as well as gene mapping data are reported for three members of a
      Portuguese Caucasian family with high G(gamma)-globin levels. A gamma-globin gene
      sextuplication of the G(gamma)AG(gamma)AG(gamma)AG(gamma)AG(gamma)A(gamma) type
      was present in the proband and her father. Comparison of gene mapping data with
      quantitative results of fetal haemoglobin (HbF) analysis provided an explanation
      for the extremely high G(gamma)-globin levels (> 90%) in the HbF from the two
      mentioned individuals. This rearrangement, for which a generation mechanism is
      proposed, is the first gamma-globin gene sextuplication described in the
      literature.

PMID- 11841450
TI  - Novel alleles at the JK blood group locus explain the absence of the erythrocyte
      urea transporter in European families.
AB  - The Kidd (JK) blood group system is of importance in transfusion medicine. The
      Jk(null) phenotype is associated with absence of the urea transporter in
      erythrocytes and moderately reduced ability to concentrate urine. We and others
      recently reported different molecular alterations in the silenced Jkb-like
      alleles of Polynesians and Finns, populations with higher Jk(null) frequencies.
      Here we report novel molecular bases of this phenotype in Caucasians. Blood
      samples from a Swiss and an English family were investigated by serological
      methods, urea haemolysis test and JK genotyping. Genomic DNA and JK mRNA were
      sequenced. Genotyping showed homozygosity for Jka-like alleles. The Swiss
      Jk(null) alleles deviated from wild-type Jka sequence by a nonsense mutation in
      exon 7 causing an immediate stop codon (Tyr194stop). The English Jk(null) alleles
      revealed a genomic 1.6 kilobase pair deletion including exons 4 and 5, the former
      of which includes the translation start codon. Multiple mRNA splicing variants
      were detected in reticulocytes but exons 3-5 were absent in all transcripts
      analysed. Screening for these alleles was negative in random donors. Two novel
      molecular alterations at the JK locus were defined and a multiplex polymerase
      chain reaction method for detection of the five known silent Jk alleles was
      developed to complement JK genotyping in clinical transfusion medicine.

PMID- 11841449
TI  - Nitric oxide donor properties of hydroxyurea in patients with sickle cell
      disease.
AB  - Hydroxyurea therapy reduces the rates of vaso-occlusive crisis in patients with
      sickle cell anaemia and recent data suggest that hydroxyurea treatment can
      generate nitric oxide (NO). Nitric oxide has been proposed as a novel therapy for
      sickle cell disease via a number of pathways. We therefore sought to determine
      whether hydroxyurea has NO donor properties in patients with sickle cell anaemia
      and explore potential mechanisms by which NO production could be therapeutic.
      Venous blood was collected from 19 fasting sickle cell anaemia patients, on
      chronic hydroxyurea therapy, at baseline and 2 and 4 h after a single morning
      dose of hydroxyurea, as well as 10 patients not taking hydroxyurea. The plasma
      and red cell NO reaction products nitrate, nitrite and nitrosylated- haemoglobin
      were measured using ozone-based chemiluminescent assays (using vanadium, KI and
      I3- reductants respectively). Consistent with NO release from hydroxyurea,
      baseline levels of total nitrosylated haemoglobin increased from 300 nmol/l to
      500 nmol/l (P = 0.01). Plasma nitrate and nitrite levels also significantly
      increased with peak levels observed at 2 h. Glutathionyl-haemoglobin levels were
      unchanged, while plasma secretory vascular cellular adhesion molecule-1 levels
      were reduced in patients taking hydroxyurea (419 +/- 40 ng/ml) compared with
      control patients with sickle cell anaemia (653 +/- 55 ng/ml; P = 0.003), and were
      inversely correlated with fetal haemoglobin levels (r = -0.72; P = 0.002). These
      results demonstrate that hydroxyurea therapy is associated with the intravascular
      and intraerythrocytic generation of NO. The role of NO in the induction of fetal
      haemoglobin and possible synergy between NO donor therapy and classic cytostatic
      and differentiating medications should be explored.

PMID- 11841452
TI  - Iron deficiency can upregulate expression of transferrin receptor at both the
      mRNA and protein level.
AB  - Expression of the transferrin receptor (TfR) is controlled essentially by post
      transcriptional regulation, which is mediated by the interaction between iron
      regulatory proteins (IRPs) and iron-responsive elements (IREs) located in the 3'
      untranslated region (UTR) of TfR mRNA. We examined whether additional controls of
      expression might occur by investigating the regulation of TfR in the absence of
      its' IREs by cloning 3'-UTR truncated TfR cDNA (TfRDeltaIRE) into pcDNA3.1(+) and
      stably expressing it in CHO-TRVb (Chinese Hamster Ovary, TfR variant cells, clone
      b) cells which have no endogenous TfR. Both the surface and the total cell TfR
      protein levels increased significantly after treating the stably transfected
      cells with the iron chelator desferrioxamine (DFO) compared with the control
      cells. In contrast, expression of the transferrin receptor 2 (TfR2), which was
      also cloned in the same vector and stably expressed in the TRVb-CHO cells, was
      not regulated by iron chelation. In addition, TfR2 fused to the 3'-UTR of TfR
      (TfR2-IRE) was cloned into the same vector and stably expressed in the CHO-TRVb
      cells. A comparison showed that expression of full-length TfR and TfR2-IRE
      increased by fivefold and twofold, respectively, after addition of DFO. Further
      experiments showed that TRVb-CHO cells, which were stably transfected with
      TfRDeltaIRE and exposed to either normal medium or DFO, resulted in similar
      levels of TfR mRNA, but the TfR protein biosynthetic rate increased with iron
      chelation. In summary, expression of TfR in cells placed in an iron-deficient
      milieu can increase by a mechanism which is independent of the IREs of TfR.

PMID- 11841453
TI  - Anti-CD20 monoclonal antibody (Rituximab) for life-threatening autoimmune
      haemolytic anaemia in a patient with systemic lupus erythematosus.
AB  - Innovative approaches are needed for patients with systemic lupus erythematosus
      (SLE) who develop autoimmune haemolytic anaemia (AIHA) that does not respond to
      conventional treatment. Rituximab, a chimaeric anti-CD20 monoclonal antibody, has
      been demonstrated to be highly effective for in vivo B-cell depletion. We report
      an 18-year-old-girl with SLE and life-threatening AIHA that did not respond to
      steroids, intravenous immunoglobulin and cyclosporin A. Rituximab was given
      weekly at 375 mg/m2 for two doses. The drug was well tolerated and the patient
      had no adverse effects. Her haemolytic disorder markedly ameliorated, with a
      progressive increase of haemoglobin levels, starting a few days after therapy.
      The patient remains disease-free 7 months later.

PMID- 11841454
TI  - Mobilization of peripheral blood stem cells with chemotherapy and recombinant
      human granulocyte colony-stimulating factor (rhG-CSF): a randomized evaluation of
      different doses of rhG-CSF.
AB  - To date, no randomized study has compared different doses of recombinant human
      granulocyte colony-stimulating factor (rhG-CSF) following submyeloablative
      mobilization chemotherapy. Therefore, we evaluated the effect of different doses
      of rhG-CSF following mobilization chemotherapy on yields of CD34+ peripheral
      blood stem cells (PBSC). Fifty patients were randomized to receive 8 (n = 25)
      versus 16 microg/kg/d (n = 25) of rhG-CSF following mobilization chemotherapy.
      The median number of CD34+ cells collected after 8 microg/kg/d of rhG-CSF was
      2.36 x 10(6)/kg (range, 0.21-7.80), compared with 7.99 (2.76-14.89) after 16
      microg/kg/d (P < 0.001). Twenty out of 25 (80%) patients in the low-dose and 23
      out of 25 (92%) in the high-dose rhG-CSF arm underwent high-dose chemotherapy
      (HDC) and autologous stem cell transplantation (ASCT). Median days to white blood
      cell engraftment in patients mobilized with 8 microg/kg and 16 microg/kg of rhG
      CSF were 12 (10-20) and 9 (8-11) respectively (P < 0.001). There was no
      difference between the two groups regarding the other parameters of
      peritransplant morbidity: days to platelet engraftment (P = 0.10), number of red
      blood cell (P = 0.56) and platelet transfusions (P = 0.22), days of total
      parenteral nutrition requirement (P = 0.84), fever (P = 0.93) and antibiotics (P
      = 0.77), and number of different antibiotics used (P = 0.58). These data showed
      that higher doses of rhG-CSF following submyeloablative mobilization chemotherapy
      were associated with a clear dose-response effect based on the collected cell
      yields. Based on the parameters of peritransplant morbidity, 8 microg/kg/d was as
      effective as 16 microg/kg/d except for a rapid neutrophil engraftment in the high
      dose arm. Therefore, in routine clinical practice, despite some advantage in the
      use of higher doses of rhG-CSF, lower doses may be used for PBSC collections
      following chemotherapy-based mobilization regimens in this cost-conscious era.

PMID- 11841455
TI  - Invasive fungal infections after allogeneic peripheral blood stem cell
      transplantation: incidence and risk factors in 395 patients.
AB  - We have analysed the incidence and risk factors for the occurrence of invasive
      fungal infections (IFI) among 395 recipients of an allogeneic peripheral blood
      stem cell transplantation (PBSCT) from a human leucocyte antigen (HLA)-identical
      sibling. IFI (n = 50) occurred in 46 patients, giving an overall probability of
      14%. There were 12 cases of invasive candidiasis (3%), with only one death. Non
      Candida IFI occurred in 37 patients (12% probability), mostly invasive
      aspergillosis (n = 32). In multivariate analysis the only two significant
      variables associated with a higher risk of developing a non-Candida IFI were the
      development of moderate-to-severe graft-versus-host disease (GvHD, P < 0.0001; OR
      4.6) and having received steroid prophylaxis for GvHD (P = 0.04; OR 2.1). In
      multivariate analysis the variables associated with a lower overall survival
      after PBSCT were development of a non-Candida IFI (P < 0.0001; OR 5.6), non-early
      disease phase (P = 0.0001; OR 1.9), steroid prophylaxis (P = 0.02; OR 1.4),
      moderate-to-severe GvHD (P = 0.01; OR 1.6) and cytomegalovirus infection post
      transplant (P = 0.001; OR 1.8). Our results show that non-Candida IFI (in
      particular aspergillosis) was an important cause of infectious morbidity and
      mortality after an HLA-identical sibling PBSCT, while invasive candidiasis was
      rare. Use of steroid prophylaxis and, in particular, the development of moderate
      to-severe GvHD post transplant were risk factors for non-Candida IFI.
      Prophylactic strategies for these infections should thus take into account these
      risk factors.

PMID- 11841456
TI  - Single-centre experience with allogeneic bone marrow transplantation for acute
      lymphoblastic leukaemia in childhood: similar survival after matched-related and
      matched-unrelated donor transplants.
AB  - Seventy percent of children with acute lymphoblastic leukaemia (ALL) who may
      benefit from bone marrow transplant (BMT) lack a human leucocyte antigen (HLA)
      matched related donor (MRD). For these children, BMT from a matched unrelated
      donor (MUD) represents a therapeutic option. We reviewed the course of 62
      children with ALL who received fully matched marrow allografts at our institution
      between 1990 and 1998: 36 with MRDs and 26 with MUDs. Clinical characteristics
      were similar in the two groups. The interval from attainment of pre-BMT complete
      remission to transplant was significantly longer in the MUD group. Conditioning
      (etoposide/total body irradiation) and graft-versus-host disease (GVHD)
      prophylaxis regimens were the same for all patients, and all received T cell
      replete bone marrow. There was no significant difference in probability of
      engraftment, or time to engraftment, in the two groups. MUD BMT recipients had a
      significantly greater incidence of grade II-IV acute GVHD (58% versus 24% in the
      MRD group; P = 0.02), and demonstrated a trend towards more chronic GVHD (39%
      versus 15%; P = 0.06). Three years post BMT, the probabilities of transplant
      related mortality were 33 +/- 11% and 20 +/- 8% in MUD and MRD groups
      respectively (P = 0.38); the probabilities of relapse were 28 +/- 12% and 41 +/-
      9% respectively (P = 0.19). Lansky or Karnofsky performance scores in event-free
      survivors were 90-100 in 87% of the MUD group and 83% of the MRD group. With a
      median follow up of 38 months (range, 3-97), 3-year event-free survival was 49 +/
      11% and 47 +/- 9% in the MUD and MRD BMT groups respectively (P = 0.71). These
      results suggest that MUD BMT is a valuable therapy for children with ALL in whom
      BMT is indicated, and underscore the importance of efforts aimed at expediting
      unrelated donor searches for patients lacking a MRD.

PMID- 11841457
TI  - Long-term follow-up of recipients of allogeneic bone marrow grafts reveals no
      progressive telomere shortening and provides no evidence for haematopoietic stem
      cell exhaustion.
AB  - Accelerated telomere shortening has been proposed as a possible long-term risk of
      allogeneic bone marrow transplantation (allo-BMT). In this study we monitored
      telomere length in white blood cells (WBC), granulocytes, and naive and memory
      CD4+ T lymphocytes in recipients of allo-BMT at long-term follow-up. Peripheral
      blood was collected from 10 allo-BMT recipients and donors at a median interval
      of 18 years after allo-BMT. Telomere length was determined using Southern blot
      analysis. Similar to results previously reported at short-term follow-up, a small
      difference in telomere length (0.1-0.3 kb) between recipients and donors was
      detected in WBC, granulocytes and naive CD4+ T cells. Our data therefore provide
      no evidence for sustained telomere shortening in leucocytes, and render the
      possibility of long-term haematopoietic graft failure unlikely. In addition, we
      observed two phenomena that may be related to involution of the thymus. First,
      the number of naive CD4+ T cells in the blood was significantly lower in
      recipients (0.4 x 10(9)/l) than in donors (0.7 x 10(9)/l) (P < 0.05). Second,
      telomeres in memory CD4+ T cells from recipients were on average 0.6 kb shorter
      than those from donors (P = 0.01). The latter may be related to the reported
      rapid peripheral expansion of memory T cells immediately after transplantation.

PMID- 11841458
TI  - Non-myeloablative bone marrow transplantation in an adult with Wiskott-Aldrich
      syndrome.
AB  - Early bone marrow transplant is now standard treatment for infants with severe
      immunodeficiencies such as Wiskott-Aldrich Syndrome (WAS), but results in older
      children and adults are poor. Non-myeloablative transplant has shown promise in
      the treatment of older children, who are likely to have active infections and
      organ damage. We describe a non-myeloablative transplant of a 26-year-old man
      with WAS, undertaken because of severe infections and vasculitis. Partial
      engraftment and immunorestoration were achieved. The patient is well 1 year post
      transplantation.

PMID- 11841459
TI  - Type of post-grafting immunosuppression after non-myeloablative blood cell
      transplantation may influence risk of delayed haemolysis due to minor ABO
      incompatibility.

PMID- 11841460
TI  - Clinical management of the avulsed tooth: present strategies and future
      directions.
AB  - The aim of this review article is to supplement the recently published
      International Association of Dental Traumatology (IADT) guidelines on treatment
      of the avulsed tooth. A thorough discussion on the reasoning behind each
      guideline is presented. In addition, the author's views on alternate treatment
      strategies and future directions, along with recent research on the subject of
      the avulsed tooth, are also presented.

PMID- 11841461
TI  - Effects and distribution of the enamel matrix derivative Emdogain in the
      periodontal tissues of rat molars transplanted to the abdominal wall.
AB  - The enamel matrix derivative Emdogain (EMD) has been found to promote
      regeneration of lost periodontal tissues. We have studied the effects and
      distribution of EMD in the periodontal tissues of maxillary rat molars
      transplanted to a subcutaneous position in the abdominal wall. The molars were
      transplanted with or without EMD either immediately after extraction or after
      drying for 30 min. After 2 days, 1, 2 or 4 weeks the rats were killed and the
      teeth were examined by means of light microscopy and immunohistochemistry with
      anti-amelogenin antibodies. Teeth transplanted immediately after extraction
      showed formation of alveolar bone separated from the dental roots by a
      periodontal space, regardless of the use of EMD. Among the teeth that were
      transplanted with EMD after drying for 30 min, new alveolar bone was formed in
      five out of eight teeth after 2 and 4 weeks. None of the teeth that were dried
      for 30 min and transplanted without EMD showed alveolar bone formation. Only one
      tooth transplanted with EMD showed root resorption after drying, while resorption
      was noted in all teeth transplanted without EMD. All teeth that were transplanted
      with EMD and none of the teeth that were transplanted without EMD showed an
      immunohistochemical reaction for amelogenin. After 2 days, amelogenin was
      precipitated on all surfaces exposed at the transplantation procedure. Later, the
      immunoreactive material was redistributed to cells at the root surface, where it
      was still demonstrable after 4 weeks. In conclusion, EMD is accumulated in cells
      at the root surface and promotes regeneration of the periodontal tissues of the
      transplanted teeth. It also seems to promote healing of root resorption.

PMID- 11841462
TI  - EVA mouthguards: how thick should they be?
AB  - A major consideration in the performance of mouthguards is their ability to
      absorb energy and reduce transmitted forces when impacted. This is especially
      important to participants in contact sports such as hockey or football. The
      thickness of mouthguard materials is directly related to energy absorption and
      inversely related to transmitted forces when impacted. However, wearer comfort is
      also an important factor in their use. Thicker mouthguards are not user-friendly.
      While thickness of material over incisal edges and cusps of teeth is critical,
      just how thick should a mouthguard be and especially in these two areas?
      Transmitted forces through different thicknesses of the most commonly used
      mouthguard material, ethylene vinyl acetate (EVA) (Shore A Hardness of 80) were
      compared when impacted with identical forces which were capable of damaging the
      oro-facial complex. The constant impact force used in the tests was produced by a
      pendulum and had an energy of 4.4 joules and a velocity of 3 meters per second.
      Improvements in energy absorption and reductions in transmitted forces were
      observed with increasing thickness. However, these improvements lessened when the
      mouthguard material thickness was greater than 4 mm. The results show that the
      optimal thickness for EVA mouthguard material with a Shore A Hardness of 80 is
      around 4 mm. Increased thickness, while improving performance marginally, results
      in less wearer comfort and acceptance.

PMID- 11841463
TI  - Rate of infraposition of reimplanted ankylosed incisors related to age and growth
      in children and adolescents.
AB  - In growing individuals, infraposition of a reimplanted, ankylosed tooth may
      disrupt normal alveolar development and compromise prosthetic treatment. The aims
      of this study were to analyze the rate of infraposition of ankylosed incisors in
      growing subjects and to provide guidelines for the timing of extraction. The
      subjects comprised 30 boys and 12 girls, selected consecutively from patients on
      annual post-trauma follow-up, and observed for periods ranging from 1 to 10
      years. Only patients with one replanted ankylosed maxillary central incisor were
      included, the homologous teeth with healthy periodontal ligaments serving as
      controls. Growth intensity was evaluated from analyses of annual body height
      measurements. The following four periods were established: before the growth
      spurt, from initial to maximal growth spurt, from maximal growth spurt to the end
      and after the growth spurt. In 11 patients, cephalograms were taken at diagnosis
      and at extraction. Progression of infraposition varied individually. Diagnosis
      before the age of 10 or before the growth spurt was associated with very high
      risk of severe infraposition. In these cases the ankylosed tooth should be
      removed within 2-3 years. If ankylosis develops during the growth spurt, the
      tooth should be monitored regularly, but no intervention is indicated provided
      the adjacent teeth do not tilt and infraposition is minor or stable. Annual body
      height measurements, indicating the intensity of skeletal growth, are an aid to
      assessment. Cephalometric radiographs are important for evaluating the direction
      of growth of the jaws since there is a difference between horizontal and vertical
      growers.

PMID- 11841464
TI  - Combined apexification and orthodontic intrusion of a traumatically extruded
      immature permanent incisor.
AB  - A patient with a traumatic extrusion of the maxillary right central incisor was
      referred to the Pedodontic Clinic of Gazi University Faculty of Dentistry after
      15 days. Orthodontic repositioning of the tooth was planned in 6 months. At the
      beginning of orthodontic therapy it was observed that the tooth was necrotic and
      needed an apexification procedure. The apexification procedure and orthodontic
      intrusion were successfully performed at the same time. In addition, a "walking
      bleach" was performed after the orthodontic and endodontic procedures were
      completed. At the 3-year recall, the tooth appeared normal in all respects.

PMID- 11841465
TI  - Vertical root fracture treated by bonding fragments and rotational replantation.
AB  - These case reports describe a new treatment method for complete vertical root
      fractures. This method is composed of two steps. First, the fractured tooth is
      intentionally extracted atraumatically, and then the separated fragments are
      bonded with an adhesive resin cement. The restored tooth is replanted by rotating
      approximately 180 degrees into the original socket and fixing with an orthodontic
      wire. For both cases reported here, bone regeneration was observed at the 3-year
      follow-up. Since this modality adopts the respective advantages of both
      intentional replantation and adhesive treatment, it might be the treatment of
      choice in cases of vertical root fracture.

PMID- 11841467
TI  - Ban human cloning.

PMID- 11841468
TI  - Cloning of Homo sapiens? No!
AB  - Animal cloning by nuclear transplantation was first developed in the northern
      leopard frog, Rana pipiens. It was soon extended to other amphibian species and
      within time, to various mammalian species. The production of a cloned sheep
      (Dolly) from an adult nuclear donor reawakened interest in human cloning. Nuclear
      transfer for the production of animal clones has served experimental biology
      well. Nonetheless, the potential burden of developmental hazards, scientists and
      funds diverted from more needy causes, as well as the potential assault on the
      concept of family has led the author to oppose human cloning.

PMID- 11841469
TI  - Commentary on human cloning.

PMID- 11841470
TI  - Recent progress and problems in animal cloning.
AB  - It is remarkable that mammalian somatic cell nuclei can form whole individuals if
      they are transferred to enucleated oocytes. Advancements in nuclear transfer
      technology can now be applied for genetic improvement and increase of farm
      animals, rescue of endangered species, and assisted reproduction and tissue
      engineering in humans. Since July 1998, more than 200 calves have been produced
      by nuclear transfer of somatic cell nuclei in Japan, but half of them were
      stillborn or died within several months of parturition. Morphologic abnormalities
      have also been observed in cloned calves and embryonic stem cell-derived mice. In
      this review, we discuss the present situation and problems with animal cloning
      and the possibility for its application to human medicine.

PMID- 11841471
TI  - Epigenetics by DNA methylation for development of normal and cloned animals.

PMID- 11841472
TI  - Biotechnology in reproductive medicine.
AB  - In this review I am summarizing the past and current progress in the field of
      pharmaceutical, diagnostic, therapeutic, and reproductive cloning in mammals.
      Several human gene products can be pharmaceutically explored in transgenic farm
      animals and employed for medical applications. Preimplantation genetic diagnosis
      (PGD) is utilizing modern molecular cloning techniques to detect genetic and
      chromosomal aberrations in early embryos originating from patients with inborn
      errors at risk for hereditary diseases or age-related risk for abnormal
      karyotype. Stem cell engineering from early human embryos is creating new and
      promising but also controversial applications for therapeutic and regenerative
      medicine. Potential risk factors for reproductive cloning are presented and
      discussed in the context of possible developmental malformations, frequently
      observed after embryo culture and cloning in farm animals. Future extension of
      biotechnology to human reproductive cloning is currently under worldwide dispute.

PMID- 11841473
TI  - Abnormal in utero development of cloned animals: implications for human cloning.

PMID- 11841474
TI  - Why care about the ethics of therapeutic cloning?

PMID- 11841475
TI  - To clone or not to clone: who will answer the question?

PMID- 11841476
TI  - Cloning humans? Current science, current views, and a perspective from
      Christianity.
AB  - Therapeutic cloning is urgent and should be vigorously supported. To successfully
      argue for this position, the distinction between a human embryo and a human
      nuclear transplant may be helpful. Even if current technical difficulties should
      be solved, global legislation should prohibit cloning for the purpose of
      fabricating babies. This position originates from a view on human nature in
      general and from a Christian perspective in particular.

PMID- 11841477
TI  - Telomerase and differentiation in multicellular organisms: turn it off, turn it
      on, and turn it off again.
AB  - Telomerase is a ribonucleoprotein complex that catalyses the addition of TTAGGG
      repeats onto telomeres, repetitive DNA structures found at the ends of linear
      chromosomes. The majority of human somatic tissues do not display telomerase
      activity and undergo telomeric shortening with consecutive divisions. This
      telomeric shortening results in replicative senescence in vitro and likely in
      vivo. Telomerase activity is present in the vast majority of tumors, preventing
      telomeric shortening and thereby enabling indefinite cell divisions. Telomerase
      activity is regulated throughout human development, undergoing silencing in
      almost all organ systems from embryogenesis onwards. However, regulated
      telomerase activity is seen in basal/stem cell compartments of highly
      regenerative tissues, such as those of the immune system, skin, and intestine.
      Avian species display telomerase repression and telomeric shortening similar to
      that seen in humans. However, rodents retain telomerase-competency throughout
      their lifespan and have not been shown to display division-dependent telomere
      shortening. The regulation of telomerase activity in plants is less well
      understood, although early indications suggest ubiquitous competency. The aim of
      this review is to present current data regarding developmental regulation of
      telomerase in humans, mice, chickens and flowering plants. Differentiation,
      quiescence and telomerase activity regulation will then be addressed in three
      human representative tissue systems; blood, skin, and intestine. We will also
      highlight similarities, differences and misconceptions in the developing field of
      telomere and telomerase biology.

PMID- 11841478
TI  - Notch signaling is involved in the regulation of Id3 gene transcription during
      Xenopus embryogenesis.
AB  - During Xenopus embryogenesis, XId3, a member of the Id helix-loop-helix protein
      family, is expressed in a large variety of differentiating tissues including
      epidermis, cement gland, brain, neural tube, neural crest cell derivatives,
      somites, and tailbud. Transcription of XId3 is mediated by several cis-regulatory
      elements including an enhancer of 440 bp located 870 bp upstream from the
      transcription initiation site. The enhancer activity in embryos was studied using
      transgenic methodology. A galactosidase reporter gene, driven by a regulatory
      element composed of the enhancer and a minimal promoter derived from the XId3
      gene, was expressed in transgenic embryos with a profile that faithfully
      reproduced that of the endogenous XId3 gene. The pattern resulted from a
      synergistic effect between the enhancer and the promoter, and in vitro
      transactivation assays showed that transcription can be stimulated by Notch
      signaling. The presence of potential Su(H) binding sites, in both the enhancer
      and the promoter, suggests that these represent candidates for in vivo cis
      regulatory elements. The data presented here suggest that Notch control of
      differentiation may involve activation of transcription of Id, a negative
      regulator of bHLH transcription factors.

PMID- 11841480
TI  - Xist expression and macroH2A1.2 localisation in mouse primordial and pluripotent
      embryonic germ cells.
AB  - The molecular mechanism underlying X chromosome inactivation in female mammals
      involves the non-coding RNAs Xist and its antisense partner Tsix. Prior to X
      inactivation, these RNAs are transcribed in an unstable form from all X
      chromosomes, both in the early embryo and in undifferentiated embryonic stem (ES)
      cells. Upon differentiation, the expression of these unstable transcripts from
      all alleles is silenced, and Xist RNA becomes stabilised specifically on the
      inactivating X chromosome. This pattern of expression is then maintained
      throughout subsequent somatic cell divisions. Once established, the inactive
      state of the X chromosome is remarkably stable, the only natural case of
      reactivation occurring in XX primordial germ cells (PGCs) when they enter the
      genital ridge. To gain insight into the X reactivation process, we have analysed
      Xist gene expression using RNA FISH in PGCs and also in PGC-derived embryonic
      germ (EG) cells. XX EG cells were shown to express unstable Xist/Tsix from both X
      chromosomes. In contrast, no unstable Xist/Tsix transcripts were detected in XX
      PGCs at any stage. Instead, a proportion of XX PGCs isolated from the genital
      ridge between 11.5 and 13.5 dpc (the period during which X chromosome
      reactivation occurs) showed an accumulation of stable Xist RNA on one X. The
      number of these cells decreased progressively and was nearly extinguished by 13.5
      dpc. As a late marker for the inactive state, we analysed localisation of the
      histone H2A variant macroH2A1.2. Although macroH2A1.2 expression was observed in
      PGCs, no significant localisation to the inactive X was detected at any stage. We
      discuss these results in the context of understanding X chromosome reactivation.

PMID- 11841479
TI  - In vitro differentiation of WB-F344 rat liver epithelial cells into the biliary
      lineage.
AB  - Differentiation of hepatic precursor cells in the biliary lineage has rarely been
      investigated, owing to the lack of convenient in vitro models. In this study, we
      used sodium butyrate and culture on Matrigel to promote differentiation of WB
      F344 rat liver epithelial cells along the biliary phenotype. This differentiation
      was assessed by following the expression of phenotypic markers at the protein or
      mRNA level. Sodium butyrate induced cytokeratin 19 expression and gamma
      glutamyltranspeptidase activity, together with a large increase in gamma
      glutamyltranspeptidase mRNA IV, a transcript expressed at high levels in biliary
      cells. We also observed an increase in aquaporin-1 and beta4 integrin mRNAs,
      encoding two proteins expressed in adult biliary cells. Culture on Matrigel
      increased cytokeratin 19, gamma-glutamyltranspeptidase, and BDS7 expression in WB
      F344 cells which still expressed aquaporin-1 and beta4 integrin. These results
      show that WB-F344 cells are able to differentiate in vitro along the biliary
      pathway, making them a candidate model for analyzing the molecular events
      associated with the hepatoblast-biliary cell transition.

PMID- 11841481
TI  - Prevalence of human leukocyte antigen (HLA) DRB1 alleles in Kuwaiti children with
      juvenile rheumatoid arthritis.
AB  - The prevalence of human leukocyte antigen (HLA) DR alleles has been determined in
      69 Kuwaiti Arab children with juvenile rheumatoid arthritis (JRA) and compared to
      that in 212 ethnically matched normal healthy controls using a PCR-sequence
      specific primers (PCR-SSP) method. A very high incidence of DR3 was detected in
      JRA patients compared to the controls (P < 0.0001, RR = 2.235). The high
      incidence of HLA-DR3 in JRA patients was accounted for mainly by an excess of
      DRB1*0307 (P < 0.05, RR = 3.072) and DRB1*0308 (P < 0.009, RR = 2.663) compared
      to the controls. Moreover, DR3 was more prevalent when patients with ANA-positive
      JRA were analysed separately; 73% compared to 58% for the whole JRA patient
      group. The frequency of DR1 was also higher in the JRA group compared to controls
      (P = 0.019, RR = 3.585). Although the incidence of some alleles was higher in the
      control group (DR13 and DR7), none reached a statistically significant level. All
      the patients with iridocyclitis had either a DR1 or DR3 allele, except for one
      child. The frequency of DRB1*03 was found to be much higher in the polyarticular
      subtype of Kuwaiti JRA cases compared to the oligoarticular subgroup and the
      controls. Also, a non-significant increase in the frequency of the DRB1*04, *11
      and *15 alleles was detected in the polyarticular subtype of the Kuwaiti JRA
      cases compared to the controls.

PMID- 11841482
TI  - Polymorphisms of tumour necrosis factors A and B in breast cancer.
AB  - We assayed for germline single nucleotide polymorphisms (SNPs) in the TNFB and
      TNFA genes in patients with breast cancer. SNPs were observed in the first intron
      of TNFB (G/A) and at -1031 (T/C), -863 (C/A), -857 (C/T) and -308 (G/A) in the
      promoter region of TNFA from peripheral leucocytes in 95 breast cancer patients
      and 190 healthy subjects as controls. The TNFB*G/TNFB*G homozygote (23.2% vs.
      5.8%, P= 0.001) was predominant in patients, while the TNFB*A/TNFB*A homozygote
      was less frequent in patients (34.7% vs. 46.3%, P = 0.041) than in the control
      subjects. Breast cancer was not associated with SNPs in the TNFA promoters.
      Although the TNFB SNP failed to associate with any clinicopathological parameter
      of breast cancer, a substantial difference in pathology among tumour stages for
      the -857 SNP in TNFA was detected. These results indicate that TNFB has both
      tumorigenic and antitumorigenic capabilities depending on the genotype: the TNFB
      SNP TNFB*G/TNFB*G genotype gave an increased risk for breast cancer and that of
      TNFB*A/TNFB*A gave resistance to breast cancer (OR = 5.3395%; CI: 2.33-12.19).
      The results suggest that the TNFB*G allele plays some role in the tumorigenesis
      or activation of dormant tumour cells, but the TNFB*A allele induces some
      function(s) leading to the inhibition of tumorigenesis.

PMID- 11841483
TI  - TCRBV3S1 and TCRBV18 gene segment polymorphisms in Brazilian Caucasoid and Black
      populations.
AB  - The T-cell receptor (TCR) repertoire plays an important role in shaping specific
      immune responses. Genetic polymorphisms at the TCR locus, in both constant and
      variable regions, seem to represent an important mechanism for generating inter
      individual and inter-population differences. Considering the scarcity of immune
      parameters characterized for normal human populations, we decided to determine
      the frequency of two TCRBV polymorphisms (located in the TCRBV3S1 and TCRBV18
      gene segments) in two ethnically distinct groups of the general Brazilian
      population. Both polymorphisms are related to the expression of these segments at
      the T-cell surface and can consequently modulate the T-cell repertoire,
      potentially modifying the capacity of a given individual to develop an immune
      response. These DNA polymorphisms were analysed in material obtained from adult,
      normal South-American Caucasoid and Black individuals. A total of 139 individuals
      were analysed for the TCRBV3S1 and 141 for the TCRBV18 gene segment
      polymorphisms. The data indicated statistically significant differences in
      allelic frequencies for the two ethnic groups analysed, suggesting that any
      correlation between TCR usage or T-cell repertoire and development of a given
      disease should take in account the ethnic origin of the population studied.

PMID- 11841484
TI  - Influence of TNFalpha and LTalpha single nucleotide polymorphisms on
      susceptibility to and prognosis in cutaneous malignant melanoma in the British
      population.
AB  - Cutaneous malignant melanoma (CMM) is a potentially fatal malignancy in which
      exposure to UV light is the most important risk factor. Several lines of evidence
      suggest that increased expression of tumour necrosis factor (TNF) alpha,
      upregulated by UV exposure, may contribute to tumour escape from the immune
      response. In this study, we addressed whether single nucleotide polymorphisms
      (SNPs) in the TNFalpha promoter and lymphotoxin (LT) alpha gene are associated
      with susceptibility to or known prognostic indicators (e.g. initial tumour growth
      phase, Breslow thickness, mitotic count in vertical growth phase tumours, and
      tumour regression) in CMM. One hundred and forty-six British Caucasian CMM
      patients and 220 controls were typed for TNFalpha-376, -308 and -238 and
      LTalpha+252 SNPs by ARMS-PCR. Only the TNFalpha -238 GG (P = 0.05) and GA (P =
      0.03) genotypes showed slight, but significant, associations with CMM, while
      LTalpha+252 AA was associated with a higher mitotic count in vertical growth
      phase tumours (P = 0.02). Both TNFalpha-238 and LTalpha+252 SNPs showed linkage
      disequilibrium with HLA-DQB1*0303 and *0301 alleles, variably implicated in CMM
      susceptibility/prognosis. In addition, TNFalpha-238, -308, LTalpha+252 haplotypes
      were assigned and compared. The GGA haplotype showed a modest association with
      CMM (P = 0.04) and with stage of disease (P = 0.03) and initial growth phase in
      CMM (P = 0.02), but these associations were only significant when P-values were
      uncorrected. Unlike basal cell carcinoma, these preliminary findings suggest that
      genetic variation associated with differential TNFalpha and LTalpha production is
      unlikely to play a major, independent role in susceptibility to, and perhaps
      prognosis in, CMM.

PMID- 11841485
TI  - Genetic analysis of the interleukin-1 receptor antagonist and its homologue IL
      1L1 in alopecia areata: strong severity association and possible gene
      interaction.
AB  - Alopecia areata is an inflammatory hair loss disease with a major genetic
      component. The presence of focal inflammatory lesions with perifollicular T-cell
      infiltrates reflects the importance of local cytokine production in the
      pathogenesis. In addition to its fundamental pro-inflammatory role, the
      interleukin-1 (IL-1) system has major effects on hair growth regulation in vitro,
      with the inhibitory actions of IL-1alpha and IL-1beta being opposed by the
      receptor antagonist IL-1ra. The novel interleukin-1 like molecule 1 (IL-1L1)
      which has greatest gene sequence homology with IL1RN, the gene encoding IL-1ra,
      is another potential IL-1 antagonist. In view of previous studies suggesting a
      significant role for IL1RN polymorphisms in the pathogenesis of
      autoimmune/inflammatory disease, we have analysed polymorphisms of IL-1ra
      (IL1RN+2018) and its homologue IL-1L1 (IL1L1+4734) in a case-control association
      study on 165 patients and a large number of matched controls. Homozygosity for
      the rare allele of IL1RN (IL1RN*2) was significantly associated with alopecia
      areata [odds ratio (OR) = 1.89, 95% CI (1.09, 3.28); P = 0.02], confirming our
      previous findings of significant association with the IL1RN variable number
      tandem repeat (VNTR). The results also revealed a novel association involving a
      polymorphism of the interleukin-1 receptor antagonist homologue IL1L1 at position
      + 4734, IL1RN+2018, and alopecia areata. The effect of a genotype combining three
      copies of the rare alleles at the IL1RN and IL1L1 loci conferred a more than
      additive increase in the risk of disease compared to IL1RN+2018 or IL1L1+4734
      alone [OR 3.37 (1.60, 7.06); P = 0.002], suggesting possible synergy between the
      IL1RN and IL1L1 genes. This effect was stronger in patients with severe disease
      (alopecia totalis/universalis) [OR 4.62 (1.87, 11.40), P = 0.0022], and in those
      with early age at onset (< 20 years) [OR = 6.38 (2.64, 15.42), P = 0.0002]. Our
      results suggest that these polymorphisms within IL1RN and IL1L1 themselves or a
      gene in linkage disequilibrium with IL1RN and IL1L1 predispose to the more severe
      forms of alopecia areata.

PMID- 11841486
TI  - Association between two tumour necrosis factor intronic polymorphisms and HLA
      alleles.
AB  - The gene for tumour necrosis factor (TNF) lies at the telomeric end of the class
      III region of the major histocompatibility complex (MHC). Polymorphisms within
      this gene have been implicated in the genetic background of a large number of
      common human diseases. Recently two polymorphisms, TNF +489 and +691, have been
      described in the first intron of TNF (+489, G to A transition; +691, G deletion)
      and disease associations have been reported; however, the pattern of linkage
      disequilibrium with other MHC alleles has not been studied. We have therefore
      studied the association of TNF alleles with HLA-DR, -DQ and -B alleles in 216
      healthy individuals from the north of England. The frequencies of the uncommon
      alleles were 0.08 (+489A) and 0.05 (+691Gdel). The +489A allele is associated
      with carriage of DRB1*1104, DQB1*0301, B18 and B35. The +691Gdel allele is
      associated with carriage of DRB1*13 *11, DQB1*0301 and B44. Knowledge of the
      pattern of association, indicating probable linkage disequilibrium, between these
      TNF alleles may be useful in studies aimed at determining the role of this locus
      in the genetic background of the large number of diseases which show genetic
      associations with MHC haplotypes.

PMID- 11841487
TI  - Further polymorphism of the MICA gene.
AB  - The MHC class I chain-related (MIC) gene family constitutes an interesting
      genetic group that is related to major histocompatibility complex (MHC) class I
      genes and is located within the MHC. The MIC gene products, MICA and MICB, have
      similar structures to HLA class I molecules. So far over 50 MICA alleles have
      been reported, which suggests that this genetic system is highly polymorphic. In
      order to investigate further the extent of MICA polymorphism we have studied
      exons 2-5 of the MICA gene in over 200 homozygous and heterozygous cell lines.
      Altogether we have identified 11 new MICA alleles and report 13 new nucleotide
      variations, one in exon 2, four in exon 3, four in exon 4, two in intron 1, one
      in intron 4 and one (a deletion) in exon 4. Eight of the 10 exonic variations are
      non-synonymous. The deletion in exon 4 leads to a frame-shift mutation and the
      introduction of a repeat of 12 leucine residues encoded by the microsatellite in
      exon 5. This study provides further evidence that the MICA gene is highly
      polymorphic. In contrast to MHC class I molecules, the polymorphic sites in MICA
      are predominantly within the alpha2 and alpha3 domains. The distribution of
      synonymous and non-synonymous substitutions suggests that there is selection for
      the polymorphic positions, which therefore define potential functional sites in
      the protein. We were also able to determine the association between MICA and HLA
      B alleles in a number of homozygous cell lines bearing extended haplotypes.

PMID- 11841489
TI  - Two new polymorphisms in the human interferon gamma (IFN-gamma) promoter.
AB  - Two new single-nucleotide polymorphisms are described within the human interferon
      gamma (IFN-gamma) promoter in a Sudanese population. One is a G to T transition
      at position -183 from the transcription start. The other is a A to G transition
      at position -155. Allelic frequency analysis indicated frequencies of 0.927 (G)
      and 0.073 (T) at position -183 and 0.977 (A) and 0.023 (G) at position -155.
      These two polymorphisms have not been detected in the Centre d'Etude du
      Polymorphisme Humain (CEPH) reference population. The polymorphism -183(G-->T)
      may alter the AP-1 binding domain and the regulation of transcription. The
      polymorphism -155(A-->G) is located close to the nuclear factor-activated T-cell
      site (NFAT site) (-168 TAAAGGAAA-160) and may affect the stability of this
      region.

PMID- 11841488
TI  - HLA-DQ and DRB1 polymorphism and susceptibility to type 1 diabetes in Jamaica.
AB  - Genetic susceptibility to type 1 diabetes is determined by a combination of HLA
      DQ and DRB1 alleles. In the present study, HLA associations with type 1 diabetes
      were investigated in the Jamaican population. DRB1 and DQ genotyping was
      performed on 45 type 1 diabetic patients and 132 control subjects born and
      resident in Jamaica. The small number of patients available for study reflected
      the low prevalence of type 1 diabetes in Jamaica. The results were compared with
      those from other African heritage populations and white Caucasians. The highest
      relative risk was associated with the DRB1*03-DQ2/DRB1*04-DQ8 genotype. Both
      DRB1*0401-DQ8 and DRB1*0408-DQ8 were positively associated with disease.
      DRB1*0408-DQ8 is uncommon amongst white Caucasians, where DRB1*0401-DQ8 is the
      major predisposing haplotype. The DRB1*1503-DQ6 haplotype was associated with
      protection from diabetes in the Jamaican population. This haplotype is rare
      amongst white Caucasians, where DRB1*1501-DQ6 is the protective haplotype. Data
      from African heritage populations suggest that DRB1*1503-DQ6 might be less
      protective than DRB1*1501-DQ6. DRB1*03-DQA1*0401-DQB1*0402 was associated with
      protection from diabetes in the Jamaican population, whereas in white Caucasians
      DRB1*08-DQA1*0401-DQB1*0402 is predisposing. These data demonstrate that
      comparison of genetic associations with type 1 diabetes in races with population
      specific DRB1-DQ haplotypes provides new information as to the exact determinants
      of disease susceptibility. Further support is provided for roles of the DQ genes
      and the DRB1 gene (or a gene in linkage disequilibrium with it) in determining
      susceptibility to type 1 diabetes.

PMID- 11841490
TI  - Promoter region polymorphism of the CD14 gene (C-159T) is not associated with
      psoriasis vulgaris.
AB  - Keratinocytes of psoriatic skin show aberrant expression of membrane-bound CD14
      (mCD14). In addition, soluble CD14 (sCD14) is elevated in the sera of psoriatic
      patients. The mechanisms leading to increased CD14 expression and secretion in
      psoriasis are poorly understood. A bi-allelic polymorphism in the promoter region
      of the CD14 gene controls CD14 expression on monocytes and sCD14 levels in the
      sera of healthy subjects. In this context, we explored the CD14 promoter region
      genotypes of 63 Finnish patients with psoriasis and 126 non-psoriatic controls
      using a new ARMS-PCR method. No differences in the CD14 genotype frequencies were
      found between the groups. Thus, our results suggest that the enhanced CD14
      expression in psoriasis is not attributable to functional variants of CD14 (
      159C/T).

PMID- 11841491
TI  - Organization of the mouse macrophage C-type lectin (Mcl) gene and identification
      of a subgroup of related lectin molecules.
AB  - A number of genes encoding C-type lectin molecules have been mapped to the
      natural killer gene complex (NKC) at the distal region of mouse chromosome 6 and
      to a syntenic region on human chromosome 12p12-p13. In addition to those
      receptors which regulate NK cell function, related structures expressed on other
      cells types have also been localized to this chromosomal region. Among these are
      a number of recently characterized genes, including macrophage C-type lectin
      (MCL), macrophage-inducible C-type lectin (Mincle), dendritic cell immunoreceptor
      (DCIR) and dendritic cell-associated lectin-2 (Dectin-2). The amino acid
      sequences comprising the single C-type lectin domains of MCL, Mincle, DCIR and
      Dectin-2 are shown here to be closely related to each other. These molecules show
      overall similarity to two groups of animal C-type lectins, groups II and V, which
      demonstrate type II transmembrane topology. In this study, sequence analysis
      suggests that MCL, Mincle, DCIR and Dectin-2 represent a subset of group II
      related C-type lectins which may participate in analogous recognition events on
      macrophages and dendritic cells. The genomic organization of the MCL gene and the
      sequence of the promoter region, with putative regulatory elements, were
      determined from a mouse MCL genomic DNA clone and are described here in detail.

PMID- 11841492
TI  - A BAC contig of approximately 400 kb contains the classical class I major
      histocompatibility complex (MHC) genes of cattle.
AB  - A cattle BAC library derived from an MHC homozygous animal was screened for MHC
      class I genes. This revealed at least nine class I-related genes in a contig
      spanning approximately 400 kb, and several additional genes on other clones. The
      three classical class I genes expressed on this haplotype (A14) were shown to be
      distributed over a region at most 212 kb apart.

PMID- 11841493
TI  - Confirmation of a recombinant allele B*5603 and a hypothetical reciprocal hybrid.
AB  - From its DNA sequence, B*5603 is thought to be a product of gene conversion. We
      present here serological evidence of such an event and further speculate on a
      possible reciprocal hybrid yet to be identified. In addition, we report the
      allelic frequency of B*5603 in the Taiwanese population and its association with
      A*1101, Cw*01 and DRB1*1201.

PMID- 11841494
TI  - CD45 exon 4 point mutation does not confer susceptibility to type 1 diabetes
      mellitus or Graves' disease.
AB  - A point mutation in the leukocyte common antigen (CD45, C-->G77, exon 4) was
      investigated in patients with type 1 diabetes (IDDM), patients with Graves'
      disease and controls. The distribution did not differ significantly between
      patients and controls. This CD45 variant does not therefore confer susceptibility
      to either IDDM or Graves' disease.

PMID- 11841495
TI  - Molecular analysis of HLA-DRB1 polymorphism in north-east Spain.
AB  - The DRB1* polymorphism in 941 randomly selected individuals from the Umbilical
      Cord Blood Bank of Barcelona (92.75% of Spanish origin) was determined by
      sequence-based typing. The HLA profile was similar to that of other Mediterranean
      populations, with DRB1*0701 and *0301 being the most frequent alleles. This may
      be a consequence of the mixture of alleles as a result of migration from
      contiguous geographical areas.

PMID- 11841496
TI  - Nomenclature for factors of the HLA System, update September 2001.

PMID- 11841497
TI  - Germ-line transformation of the Australian sheep blowfly Lucilia cuprina.
AB  - The Australian sheep blowfly, Lucilia cuprina, is the most important economic
      insect pest for the sheep industries in Australia and New Zealand. piggyBac
      mediated germ-line transformation of L. cuprina was achieved with a helper
      plasmid that had the Drosophila melanogaster hsp70 promoter controlling
      expression of the transposase and a piggyBac vector with an EGFP marker gene. Two
      transformant lines were obtained, at a frequency of approximately 1-2% per
      fertile G0. One of these lines has a single copy of the transgene, the other most
      likely has four copies. This is the first report of germ-line transformation of
      L. cuprina and is an important step towards the generation of engineered strains
      that would be suitable for male-only release eradication/suppression programmes.

PMID- 11841498
TI  - Evidence for genetic differentiation between the molecular forms M and S within
      the Forest chromosomal form of Anopheles gambiae in an area of sympatry.
AB  - We studied genetic variation at ten microsatellite DNA loci in Anopheles gambiae
      populations from the Forest chromosomal form collected in four villages in
      Cameroon (Central Africa). Both recently described M and S molecular forms occur
      in sympatry in this area. Geographic differentiation within form was low (Fst <
      0.017) despite geographical distance between collection sites ranging from 35 to
      350 km. However, higher (Fst > 0.035) and statistically significant levels of
      genetic differentiation were observed between forms, being the highest between
      sympatric M and S populations collected within the same village. Results were
      consistent across all loci spread throughout the genome, therefore reflecting a
      genome-wide pattern. Considering previous findings of strong assortative mating
      within forms and general lack of hybrids in areas of sympatry, we propose that
      there is now sufficient direct and indirect evidence to consider both M and S
      molecular forms of An. gambiae as distinct species that have probably speciated
      recently.

PMID- 11841499
TI  - Characterization of genomic DNA encoding cecropins from an Aedes albopictus
      mosquito cell line.
AB  - We used cDNA probes from Aedes albopictus mosquito cecropins AalCecA, B, and C to
      obtain genomic DNA copies and flanking DNA. Two gene copies (AalCecA1 and A2,
      AalCecB1 and B2, AalCecC1 and C2) encoding each of the three mature cecropin
      peptides were recovered. All these genes had a similar organization, into two
      exons interrupted by a single short intron. AalCecA1 and AalCecA2 encode mature
      protein products that differ by one amino acid residue, while AalCecB1 and
      AalCecB2, AalCecC1 and AalCecC2 encode identical mature cecropin peptides,
      respectively. The AalCecB and C gene pairs each share a common intergenic region
      of approximately 1 kb, with the two coding regions transcribed in opposite
      directions. With the exception of small insertions/deletions, the intergenic
      spacer region was highly conserved between the B1/C1 and B2/C2 clones. In
      transfected cells, 0.8 kb of upstream sequence was sufficient for inducible
      expression of AalCecA1. Within this region, a 28 bp sequence at positions -192 to
      -165 upstream of the transcription initiation site was found to contain a
      potential regulatory element. In electrophoretic mobility shift assays, synthetic
      double-stranded DNA containing this 28 bp sequence retarded protein in
      cytoplasmic and nuclear extracts from C7-10 cells.

PMID- 11841500
TI  - Identification and characterization of a Drosophila homologue of ATBP.
AB  - ATBP [(A+T)-stretch binding protein] activates the Sarcophaga defense protein
      genes in an (A+T)-stretch dependent manner as shown previously using a luciferase
      reporter assay [Aozasa et al. (2001) Eur J Biochem, 268, 2506-2511]. We
      identified the Drosophila homologue of ATBP. Drosophila ATBP has 388 amino acid
      residues and the amino acid sequence has high similarity with that of the
      Sarcophaga ATBP. In particular, residues 1-56 and 301-374 are highly conserved
      between Sarcophaga and Drosophila. Drosophila ATBP activated the Sarcophaga
      lectin gene promoter in SL-2 cells. The Drosophila ATBP gene is a single copy
      gene and is located in the 20E region of chromosome X.

PMID- 11841501
TI  - Population structure of the tsetse fly Glossina pallidipes estimated by allozyme,
      microsatellite and mitochondrial gene diversities.
AB  - Diversities at nuclear and mitochondrial loci were examined in eleven natural
      populations of Glossina pallidipes from east and southern Africa. Alleles in each
      class of loci are assumed to be selectively neutral. Allozyme gene diversities
      (heterozygosities) averaged over eight loci were 0.146 among seven Kenya
      populations and 0.201 among four southern African populations. Microsatellite
      diversity averaged over three loci was 0.250 in Kenya and only 0.218 in southern
      Africa. Mitochondrial diversities averaged 0.504 in Kenya and only 0.156 in
      southern Africa. Mitochondrial and microsatellite diversities in the populations
      were strongly correlated with each other, but uncorrelated with allozyme
      diversities. In contrast to the allozyme diversities, mitochondrial and
      microsatellite variation indicated a severe and prolonged reduction in population
      size in southern Africa. Genetic distances among populations increased with the
      geographical distances between them. Allozyme diversities in southern populations
      were conserved. Genetic differentiation at allozyme loci among populations was
      greatly damped when compared with the other markers. The foregoing can be
      explained if allozyme diversities were maintained by balancing selection. Three
      main points emerged: genetic data confirm the historical evidence that southern
      G. pallidipes populations experienced a severe and prolonged bottleneck; allozyme
      variation was conserved in the bottlenecked populations; and gene flow among
      populations is surprisingly restricted.

PMID- 11841502
TI  - A cluster of four D7-related genes is expressed in the salivary glands of the
      African malaria vector Anopheles gambiae.
AB  - Four genes expressed in the Anopheles gambiae adult female salivary glands and
      similar in sequence to the Aedes aegypti D7 gene were identified. The genes,
      called D7-related (D7r), are included in a single cluster encompassing
      approximately six kilobases on chromosome arm 3R. The deduced proteins contain
      secretory signals and they are probably injected by the mosquito into the host
      with the saliva during blood feeding. The region of similarity to D7 encompasses
      the carboxy-terminal part of the Ae. aegypti protein and the different An.
      gambiae D7r show a degree of similarity to each other, varying from 53% to 73%.
      The weak but significant similarity to members of a wide family of insect
      proteins, including odourant- and pheromone-binding proteins, raises the
      possibility that the D7r-encoded proteins may bind and/or carry small hydrophobic
      ligands.

PMID- 11841503
TI  - Molecular characterization of three gut genes from Glossina morsitans morsitans:
      cathepsin B, zinc-metalloprotease and zinc-carboxypeptidase.
AB  - Insect gut enzymes are involved in digestion of dietary proteins. Additionally,
      these enzymes have been implicated in the process of pathogen establishment in
      several insects including the tsetse fly (Diptera:Glossinidae), which is the
      vector for African trypanosomes. Both the male and female tsetse can transmit
      trypanosomes and are strict blood feeders during all stages of their development.
      Here, we describe the molecular characterization of three gut genes: cathepsin B
      (GmCatB), zinc-metalloprotease (GmZmp) and zinc-carboxypeptidase (GmZcp). The
      cDNA for GmCatB encodes a protein for 340 amino acids with a predicted molecular
      mass of 38.2 kDa, while the 854 bp GmZmp cDNA encodes a protein of 254 amino
      acids with a molecular mass of 29 kDa. The GmZcp cDNA is 1319 bp in length and
      has a 354 amino acids open reading frame for coding a 40 kDa protein. All three
      cDNAs have signal peptide sequences associated with their N-terminal domains and
      structure analysis indicates that GmCatB and GmZmp are expressed as zymogens with
      pro-domains proteolytically removed for activity. The activation domain
      associated with the carboxypeptidase sequences is lacking in GmZcp. While GmCatB
      transcription is constitutive, teneral flies express very low levels of
      transcripts for GmZmp and GmZcp prior to the first bloodmeal. Transcription of
      all genes is induced and remains high throughout the digestion cycle within a few
      hours following the first bloodmeal ingestion. Both GmCatB and GmZcp are parasite
      responsive, with the expression of both genes being higher in trypanosome
      infected flies.

PMID- 11841504
TI  - Identification of fat-cell enhancer regions in Drosophila melanogaster.
AB  - The insect fat body is a dynamic tissue involved in maintaining homeostasis. It
      functions not only in energy storage and intermediary metabolism but also in
      detoxification, communication and the immune response. Some of these functions
      are confined to distinct groups of fat body cells. In Drosophila melanogaster,
      discrete precursor-cell clusters populate the fat body [Hoshizaki, D.K.,
      Blackburn, T., Price, C., Ghosh, M., Miles, K., Ragucci, M. and Sweis, R. (1994)
      Embryonic fat-cell lineage in Drosophila melanogaster. Development 120: 2489
      2499; Hoshizaki, D.K., Lunz, R., Ghosh, M. and Johnson, W. (1995) Identification
      of fat-cell enhancer activity in Drosophila melanogaster using P-element enhancer
      traps. Genome 38: 497-506; Riechmann, V., Rehorn, K.P., Reuter, R. and Leptin, M.
      (1998) The genetic control of the distinction between fat body and gonadal
      mesoderm in Drosophila. Development 125: 713-723]. Whether these clusters
      populate defined morphological regions or whether they represent the precursors
      to functionally similar groups of fat-body cells has not been formally
      demonstrated. We have identified a 2.1 kb enhancer region from serpent (srp), a
      GATA transcription factor gene that is sufficient to induce fat-cell formation.
      This enhancer region drives expression in specific groups of precursor-cell
      clusters, which we show give rise to defined regions of the mature embryonic fat
      body. We present evidence that srp expression in different precursor fat cells is
      controlled by independent cis-acting regulatory regions, and we have tested the
      role of trans-acting factors in the specification of some of these cells. We
      suggest that the different positional cues regulating srp expression, and
      therefore general fat-cell specification, might also be involved in the
      functional specialization of fat cells. This may be a common mechanism in insects
      to explain the origin of biochemically distinct regions of the larval/adult fat
      body.

PMID- 11841505
TI  - A high affinity serotonin- and histamine-binding lipocalin from tick saliva.
AB  - To overcome the inflammatory response in its host, the cattle-feeding, brown ear
      tick secretes histamine-binding proteins into the feeding site. These proteins
      are beta-barrels with two internal binding sites: a high-affinity (H) site for
      histamine and a site (L) for which the natural ligand is unknown. Here we report
      a related protein (SHBP), secreted by a rodent- and cattle-feeding tick, that
      traps both histamine and serotonin. The histamine-binding H site is well
      conserved in SHBP, whereas residue changes in the L-like site are consistent with
      binding of the bulkier serotonin molecule. As histamine is a key inflammatory
      mediator in cattle, while serotonin takes on this role in rodents, the
      diversification of these tick proteins may reflect host adaptation.

PMID- 11841506
TI  - Intron-dependent stimulation of marker gene expression in cultured insect cells.
AB  - We tested in a systematic fashion the effect of an intron on the level of
      luciferase expression in cultured C6/36 Aedes albopictus cells. The intron was
      inserted in both orientations, upstream and downstream of the luciferase coding
      region in two different luciferase expression vectors. The two parental
      luciferase expression vectors differed only in their promoters, one containing
      the Drosophila melanogaster actin5C promoter and the other the Autographa
      californica nuclear polyhedrosis virus hr5/ie1 enhancer/promoter. All resulting
      intron-containing constructs were tested for their ability to express luciferase
      in transient assays following electroporation into C6/36 cells. We found that the
      introns stimulate luciferase expression between twelve and sixtyfold, depending
      on the promoter. Enhanced expression was only seen when the intron was present in
      the correct orientation upstream of the luciferase ORF. When the 3' splice sites
      of the enhanced intron-containing constructs were mutated, the expression level
      dropped back to below the level of the intronless parental constructs, suggesting
      that the intron-dependent stimulation of luciferase expression is depending on
      splicing and is not due to other effects the intron may have on transcription or
      translation. The luciferase transcripts of all constructs were analysed by
      reverse transcription, PCR amplification and sequencing, and the results show a
      perfect correlation between efficient splicing of the intron and elevated levels
      of luciferase expression. Our findings have the potential to be very useful for
      boosting expression of foreign proteins in the widely used baculoviral or non
      viral systems in insect cells.

PMID- 11841507
TI  - Transovarial transmission of sugarcane white leaf phytoplasma in the insect
      vector Matsumuratettix hiroglyphicus (Matsumura).
AB  - White leaf is a serious disease of sugarcane caused by phytoplasma. The disease
      is transmitted to the plant by the leafhopper Matsumuratettix hiroglyphicus
      (Matsumura). The reservoir of phytoplasma was suspected to be weeds that grow in
      sugarcane farming areas because they can be infected with phytoplasma and show
      symptoms similar to sugarcane white leaf. However in previous work we have
      demonstrated by RFLP and sequencing that this is not the case. Here we have
      reared M. hiroglyphicus through two generations by feeding them phytoplasma free
      sugarcane grown from tissue culture. By nested-PCR followed by sequencing, we
      demonstrated the presence of the phytoplasma in eggs, nymphs and adults of the
      first and second generations thereby showing transovarial transmission. We have
      also shown by in situ PCR that phytoplasmas were widely distributed throughout
      the body of the insect. RFLP and sequencing showed that the same phytoplasma was
      present in the vector and in the plant. Together, these data point to the
      leafhopper M. hiroglyphicus as the reservoir of phytoplasma that cause sugarcane
      white leaf disease.

PMID- 11841508
TI  - Multiple forms of U2 snRNA coexist in the silk moth Bombyx mori.
AB  - Eight U2 snRNA variants were isolated from several Bombyx mori U2-specific RT-PCR
      libraries. U2 sequences and secondary structures were generated and examined in
      terms of potential RNA and protein interactions. Analysis indicated that
      nucleotide changes occurred in both stem/loop and single-stranded areas. Changes
      in the double stranded areas were either compensatory, single substitutions (e.g.
      C <--> U) or prevented the double-stranded formation of one or two base pairs.
      The polymorphisms were clustered in moderately conserved regions. Some of the
      changes observed generated stronger base pairing. Inter-species conserved protein
      or RNA-binding sites were relatively unaffected. No polymorphic sites were found
      in known functional sequences. Bombyx mori and Drosophila melanogaster U2
      sequences are 95% and 70% similar at the 5'- and the 3'-ends of the molecule,
      respectively. Phylogenetic analysis of the U2 sequences demonstrates remarkable
      conservation across species.

PMID- 11841510
TI  - Microsatellite instability in human melanocytic skin tumors: an incidental
      finding or a pathogenetic mechanism?

PMID- 11841511
TI  - Subcutaneous pseudomembranous fat necrosis: new observations.
AB  - BACKGROUND: Pseudomembranous fat necrosis is a peculiar manifestation of necrosis
      of adipose tissue characterized by formation of pseudocystic cavities lined by
      crenulated membranes. The underlying mechanism for the formation of
      pseudomembranes is unknown and numerous hypotheses have been proposed. Despite
      divergent interpretations, most authors consider necrotic fat cells to be the
      anatomic substrate for the formation of pseudomembranes. METHODS: A total of 341
      panniculitides were reviewed for the presence of pseudomembranous fat necrosis.
      The specific diagnoses were established after correlation of all available
      clinical and laboratory data with the histopathology. Special attention was given
      to the time in the evolution of the disease when the biopsy was taken. Additional
      immunohistochemical studies were performed in 12 cases. RESULTS: Thirty of 341
      cases of different types of panniculitides were found to show pseudomembranous
      fat necrosis, namely: 10 of 15 cases of sclerosing panniculitis
      (lipodermatosclerosis), 6 of 95 cases of erythema nodosum, 7 of 34 cases of
      traumatic panniculitis, 1 of 7 cases of lupus panniculitis, 1 of 20 cases of
      erythema induratum Bazin (nodular vasculitis), 1 of 9 cases of necrobiosis
      lipoidica, 1 of 4 cases of sclerotic lipogranuloma, 1 of 9 cases of infectious
      panniculitis (erysipelas), 1 of 2 cases of pancreatic panniculitis, and 1 of 4
      cases of subcutaneous sarcoidosis. Pseudomembranous fat necrosis labelled
      strongly for the histiocytic markers CD68 and lysozyme. CONCLUSIONS: Our series
      provides data suggesting that pseudomembranous fat necrosis represents a dynamic
      process that varies according to the evolution of the lesion at the time of the
      biopsy. In biopsies taken from early foci of panniculitides pseudomembranes show
      vescicular or picnotic nuclei. Later, pseudomembranes retain their crenulated
      appearance but lack nuclear elements. Furthermore, we present histopathologic,
      histochemical, and immunohistochemical evidence that pseudomembranous fat
      necrosis results from the interaction of residual products of disintegrated fat
      cells and macrophages. Histiocytic markers such as CD68 and lysozyme may be used
      as reliable tools in order to detect pseudomembranes in panniculitides.

PMID- 11841512
TI  - Clear cell papulosis: an immunohistochemical study to determine histogenesis.
AB  - Clear cell papulosis is a rarely described disease characterized by multiple
      white maculopapules. Histopathologically, diagnostic clear cells are seen mainly
      among the basal cells of the epidermis. The origin of the clear cells has been
      thought to be eccrine or apocrine secretory cells in the epidermis because of the
      positive immunostaining with anticytokeratin antibody AE1, carcinoembryonic
      antigen (CEA), epithelial membrane antigen, and gross cystic disease fluid
      protein-15. IKH-4 and CEA have been reported to stain the eccrine secretory
      cells, but not the apocrine secretory cells. On the contrary, lysozyme has been
      reported to stain apocrine glands, but not eccrine glands. CAM5.2 has been
      reported to show a positive reaction to staining in secretory cells of eccrine
      glands, but only occasional weak staining in the inner surface of eccrine ducts.
      In our study, the clear cells in the epidermis stained with IKH-4, CEA and
      CAM5.2, but not with lysozyme. These results suggest that the clear cells may be
      eccrine secretory cells.

PMID- 11841513
TI  - Immunohistochemical and ultrastructural observations of desmoplastic
      trichoepithelioma with a special reference to a morphological comparison with
      normal apocrine acrosyringeum.
AB  - BACKGROUND: Desmoplastic trichoepithelioma is a benign neoplasm considered to
      have follicular differentiation. Its sweat gland- or sebaceous-lines of
      differentiation have been also reported. There have been, however, only a few
      reports regarding extensive immunohistochemical and ultrastructural
      investigations of this neoplasm. METHODS: Histopathological and
      immunohistochemical studies were performed on three cases of desmoplastic
      trichoepithelioma, comparing it with normal skin. One of these cases was
      ultrastructurally investigated. RESULTS: The cord-like basaloid nests were
      reacted with the anti-cytokeratin (CK)1/5/10/14, -CK5/8, -CK14 and -CK15
      antibodies, but not with the anti-CK6 antibody. Similar findings were observed in
      the outer layers of the normal follicular outer root sheath. Basaloid cell nests
      in one case, which showed ductal structures in the nests, also expressed CK7,
      CK8/18 and CK19. These keratins were also detected in the normal sweat glands. In
      addition, CK8/18 and CK19 were expressed in the basal cells of the outer root
      sheath. Keratinous cysts had inner reactions with the anti-CK10/11 and -CK6
      antibodies, and outer reactions with anti-CK5/8 and -CK14 antibodies.
      Ultrastructurally, the cells in the cord-like nests were basically immature and
      basaloid in appearance. A few cells contained Odland bodies, which were also
      observed in the normal apocrine acrosyringeum. The ductal structure was lined by
      the cells which bore numerous microvilli in the luminal surface. CONCLUSION: The
      cells in desmoplastic trichoepithelioma are suggested to be in close association
      with the basal cells in the outer root sheath, which can differentiate into
      various parts of the folliculosebaceous apocrine unit.

PMID- 11841514
TI  - A light microscopic and immunohistochemical evaluation of scars.
AB  - BACKGROUND: Scars are commonly encountered by dermatopathologists and usually do
      not present a diagnostic challenge. However, in some cases, the pathologist may
      need to consider a broad differential diagnosis including fibrohistiocytic
      tumors, smooth muscle tumors, myofibroblastic proliferations and desmoplastic
      malignant melanoma. Although specific histologic aspects of scars have been well
      studied, a complete histochemical profile of scars, especially at various stages
      of evolution, has not been described. METHODS: Twenty-five cases of scars
      including 8 normal scars, 5 hypertrophic scars and 12 keloids were studied.
      Sections were examined with Verhoeff van Giesson, colloidal iron, Giemsa, smooth
      muscle actin (SMA), CD34, Factor XIIIa and S-100. RESULTS: All scars were
      negative for CD34 expression. Factor XIIIa immunostaining identified only rare
      dermal dendrocytes. S-100 was absent in 23 of 25 cases and stained scattered
      cells (less than 10%) in the other 2 cases. SMA was positive in 14 of 25 cases
      with 6 of these showing staining of up to 50% of spindled cells. Elastic fibers
      were markedly reduced or absent in all cases, mucin showed moderate or marked
      staining in three-fourths of the cases and dermal mast cells showed a moderate
      increase in 5 cases. CONCLUSIONS: These findings confirm prior reports that
      negative staining with CD34, Factor XIIIa and S-100 can help differentiate scars
      from dermatofibrosarcoma protuberans, dermatofibroma and desmoplastic malignant
      melanoma, respectively. SMA staining is much more variable and requires careful
      interpretation.

PMID- 11841515
TI  - Benign lymphoepithelial lesion associated with squamous cell carcinoma of the
      skin: an immunohistochemical and molecular genetic study.
AB  - BACKGROUND: Benign lymphoepithelial lesions (BLEL) are usually found in salivary
      glands in autoimmune disorders. Some LEL are recognized to already be, or may
      progress to become, lymphomas. Skin lesions similar to LEL have been described in
      lymphomas, and are caused by neoplastic lymphocytes which infiltrate adnexal
      structures. To date, BLEL have not widely been recognized in the skin. METHODS:
      We describe skin lesions similar to BLELs, at the periphery of squamous cell
      carcinomas (SCC) in 8 healthy patients, in one of whom the lesion recurred.
      Immunocharacterization of both epithelial and lymphocytic components and
      molecular genetic investigation was performed. Polymerase chain reaction (PCR)
      analysis was done to detect IgH chain gene, and T-cell receptor beta and gamma
      gene rearrangements. Association with Epstein-Barr virus (EBV) was also tested by
      in situ hybridization (ISH) for EBV-encoded RNAs (EBERs). RESULTS: Epithelial
      cells showed the immunophenotype of eccrine sweat gland ducts. Infiltrating
      lymphocytes expressed overwhelming B antigens and CD5. Neither clonal B and/or T
      proliferations nor EBERs signals were demonstrable. CONCLUSIONS: We observed skin
      lesions similar to BLELs, showing modifications of sweat gland duct and CD5+, B
      lymphocytic expansion. In our cases there were no associated autoimmune
      disorders; the local immunoresponse to SCC might have caused BLEL.

PMID- 11841516
TI  - Immunohistochemical analysis of cytokeratin and human milk fat globulin
      expression in mucinous carcinoma of the skin.
AB  - BACKGROUND: Mucinous carcinoma of the skin (MCS) is a rare epithelial tumor which
      arises primarily in the skin. Metastatic MC from extracutaneous sites, especially
      breast or colon, mimics MCS and cannot be differentiated from MCS by routine
      histology alone. METHODS: Nine cases of MCS were analyzed immunohistochemically
      using monoclonal antibodies against cytokeratins (CKs) and human milk fat
      globulin 1 (HMFG) in order to clarify their nature and compare the
      immunophenotypes with those of other MCs studied in the literature. RESULTS:
      Expression of simple epithelial CKs in most of the tumor cells of all cases
      studied and co-expression of simple and stratified epithelial CKs in some tumor
      cells of two cases were recognized. CK 20 expression could not detected in any
      tumor cells. Focal HMFG expression in the luminal or outer surface of the nests
      was observed in three cases. CONCLUSION: From CKs expression, MCS was speculated
      to differentiated mainly toward the secretory cells of the sweat glands, and some
      tumor cells toward the transient portion between the dermal duct and the
      secretory portion. Focal HMFG expression suggested either a consequence of
      malignant transformation or apocrine differentiation. No expression of CK 20 in
      MCS suggests that we may exclude the diagnosis of metastatic colorectal MC which
      expressed CK 20.

PMID- 11841517
TI  - Dermatofibroma with sclerotic areas resembling a sclerotic fibroma of the skin.
AB  - BACKGROUND: Dermatofibromas are common benign tumors that occur as single or
      multiple nodules on the extremities in adults. Sclerotic fibroma of the skin
      (SFS) is a benign tumor characterized histopathologically by a well-demarcated,
      non-encapsulated dermal nodule composed of hypocellular, sclerotic collagen
      bundles with prominent clefts. The pathogenesis of these two conditions is still
      in dispute. METHODS: We present a case of dermatofibroma with sclerotic areas
      resembling a sclerotic fibroma of the skin and a review of the literature.
      RESULTS: The tumor showed a well-demarcated dermal, fibrocollagenous tumor with
      three different histopathological features. One-fourth of the lesion was
      consistent with dermatofibroma. Another area adjacent to dermatofibroma revealed
      hyalinized eosinophilic collagen bundles arranged in the characteristic
      interwoven pattern with prominent clefts, as is described in sclerotic fibroma of
      the skin. One-half of the lesion between the dermatofibroma and sclerotic fibroma
      showed transitional changes from dermatofibroma to sclerotic fibroma. CONCLUSION:
      According to these findings, the possibility that sclerotic fibroma is an ancient
      or degenerated stage of dermatofibroma cannot be completely ruled out, but some
      authors still consider that dermatofibroma and sclerotic fibroma of the skin are
      completely different neoplasms.

PMID- 11841518
TI  - Giant cell collagenoma: case report and review of the literature.
AB  - BACKGROUND: Giant cell collagenoma (GCC) is a recently described cutaneous
      fibrous neoplasm that usually affects young to middle-aged adults. Despite its
      similar histological appearance with circumscribed storiform collagenoma, no
      association of GCC with Cowden's syndrome has been described so far. To the best
      of our knowledge only five cases of this rare fibrous tumor have been reported so
      far. METHODS: We report a case of a 79-year-old male patient presenting with a
      slow growing flesh-colored dome-shaped lesion in his left forearm, with a
      clinical diagnosis of fibroma. No stigma of Cowden's syndrome was depicted.
      RESULTS: The histological analysis showed a symmetrical and well-circumscribed
      flat-dome-shaped lesion covered by an atrophic overlying epidermis. The neoplasm
      was composed of hyalinized collagen bundles disposed in a whorled storiform
      pattern. Admixed with the collagen matrix, there were two distinct cell
      populations, one composed by spindle-shaped mononuclear cells, and the other
      composed by bizarre multinucleated giant cells. Immunohistochemical analysis
      showed positivity for vimentin and actin HHF35 in the mononucleated. The
      multinucleated cells only immunoexpressed vimentin. CONCLUSION: GCC is an unusual
      cutaneous fibrous tumor that should be differentiated from circumscribed
      storiform collagenoma, pleomorphic fibroma, regressive forms of dermatofibroma,
      and solitary myofibroma based on its histological features.

PMID- 11841519
TI  - Acantholytic dyskeratotic epidermal nevus: a rare histopathologic feature.
AB  - BACKGROUND: Epidermal nevus is a congenital malformation of the epidermis
      consisting of verrucoid scaly plaques on the skin, often in a linear fashion.
      Different histologic features have been seen and, at times, acantholytic
      dyskeratosis has been observed. We report a new case of acantholytic dyskeratotic
      epidermal nevus. CASE REPORT: A 3-year-old girl presented, since birth,
      asymptomatic keratotic scaly lesions on the left hemithorax and left arm that
      followed Blaschko's lines. HISTOLOGY: Biopsies revealed acanthosis,
      papillomatosis, hyperkeratosis and focal areas of suprabasal clefting with
      acantholysis, as well as individual dyskeratotic cells (corps ronds et grains) in
      the upper layers of the epidermis. In the literature, this histologic feature has
      been reported twice. Generalized or localized Darier's disease are well
      established clinical entities with characteristic histologic features of
      acantholytic dyskeratosis. Because of the linear clinical appearance and the
      onset at birth or early childhood, the lesions should be regarded as epidermal
      nevi and not linear Darier's disease. CONCLUSION: We report here an additional
      case of dyskeratotic epidermal nevus, which is a rare histopathologic feature.

PMID- 11841520
TI  - Co-existent cutaneous cryptococcosis of the forearm and cutaneous alternariosis
      of the leg in patient with metastatic thymoma.
AB  - BACKGROUND: Cryptococcosis and alternariosis are rare opportunistic infections
      often observed in immunocompromised patients. Because Cryptococcus and Alternaria
      are ubiquitous fungi found in soil, the presence of fungi in the dermis has to be
      observed on histological examination to confirm a real cutaneous, invasive,
      infection. PATIENT: We report the first case of concomitant cutaneous
      cryptococcosis and cutaneous alternariosis, in an immunocompromised patient
      treated for a metastatic thymoma. CONCLUSION: This observation underlines the
      fact that the possible co-existence of several rare infections in
      immunocompromised patients should take into consideration pathogen identification
      in order to adapt the therapy to individual patient requirements.

PMID- 11841521
TI  - Intradermal spindle cell/pleomorphic lipoma of the vulva: case report and review
      of the literature.
AB  - BACKGROUND: Spindle cell/pleomorphic lipoma (SC/PL) is a benign adipose tissue
      tumor that usually affects the subcutaneous tissues of shoulders, backs, and neck
      region of middle-aged male patients. Histologically, it is characterized by the
      presence of primitive CD34-positive spindle cells arranged in short fascicles,
      bizarre floret-like multinucleated giant cells, mature adipocytes, and a small
      number of lipoblasts. Recently, an intradermal subset has been described, which
      mainly affects female patients and presents a wider antomical distribution when
      compared to the classical variant of SC/PL. METHODS: We report a case of
      intradermal SC/PL affecting the labium majus of a 56-year-old female patient.
      RESULTS: The histological examination disclosed the typical histological
      features, however the lesion showed poorly demarcated and infiltrative borders,
      as well as involvement of dermal nerves. The immunohistochemical analysis
      according to streptovidin-biotin-peroxidase technique showed immunoreactivity for
      CD34 and vimentin in the spindle cells, as well as S100 protein and vimentin in
      the adipocytic cells. CONCLUSIONS: To the best of our knowledge, this is the
      first case of intradermal SC/PL affecting the vulvar region. Care must be taken
      not to misdiagnosis this rare tumor as well-differentiated liposarcoma, cellular
      angiofibroma, solitary fibrous tumor, and cutaneous neurofibroma.

PMID- 11841523
TI  - Tensions in antibiotic prescribing: pitting social concerns against the interests
      of individual patients.
AB  - BACKGROUND: To reduce the prevalence of antibiotic-resistant bacteria in the
      community, physicians must optimize their use of antibiotics. However, optimal
      use from the perspective of the community (reserving newer agents for future use)
      is not always consistent with optimal use from the perspective of the individual
      patient (prescribing newer, broader agents). OBJECTIVES: To identify preferred
      patterns of antibiotic prescribing for patients with community-acquired pneumonia
      (CAP), measure explicit attitudes toward antibiotics and antibiotic resistance,
      and determine the relationship between these prescribing patterns and attitudes.
      DESIGN: Cross-sectional anonymous mail survey. PARTICIPANTS: National random
      sample of 400 generalist physicians (general internal medicine and family
      practice) and 429 infectious diseases specialists. MEASUREMENTS: Rank ordering of
      antibiotic preferences for a hypothetical outpatient with CAP and reasons for
      antibiotic selection. Endorsement of attitudes regarding antibiotic prescribing
      decisions and resistance. RESULTS: Both generalists and infectious diseases
      specialists were more likely to prefer newer, broader drugs for the treatment of
      CAP compared to older agents still recommended by national guidelines. Physicians
      rated the issue of contributing to antibiotic resistance lowest among 7
      determinants of their choices. CONCLUSIONS: Despite national guidelines and
      increasing public awareness, the public health concern of contributing to the
      problem of antibiotic resistance does not exert a strong impact on physician
      prescribing decisions for CAP. Future efforts to optimize antibiotic prescribing
      decisions will need to consider options for increasing the impact of public
      health issues on the patient-oriented decisions of individual physicians.

PMID- 11841524
TI  - Use of cholesterol-lowering therapy and related beliefs among middle-aged adults
      after myocardial infarction.
AB  - OBJECTIVE: To assess use of cholesterol-lowering therapy and related beliefs
      among middle-aged adults after myocardial infarction. DESIGN: Telephone survey
      and administrative data. SETTING: National managed-care company. PARTICIPANTS:
      Six hundred ninety-six adults age 30 to 64 surveyed in 1999, approximately 1 to 2
      years after a myocardial infarction. MEASUREMENTS: Use of cholesterol-lowering
      drugs, beliefs about the importance of lowering cholesterol, and knowledge of
      personal cholesterol level, adjusting for demographic and clinical factors with
      logistic regression. MAIN RESULTS: Among respondents, 62.5% reported they were
      taking a cholesterol-lowering drug. In adjusted analyses, these drugs were used
      significantly less often by African-American patients and those with congestive
      heart failure or peripheral vascular disease, and more often by college
      graduates, patients with hypertension, and those who had seen a cardiologist
      since their myocardial infarction. Lowering cholesterol was viewed as "very
      important"; by 87.1% of patients, but significantly less often by smokers and
      more often by those who had undergone coronary angioplasty or bypass surgery.
      Only 42.5% of respondents knew their cholesterol level, and this knowledge was
      significantly less common among less-educated or less-affluent patients, African
      American patients, and patients who smoked or had diabetes or peripheral vascular
      disease. CONCLUSIONS: Although most patients recognized the importance of
      lowering cholesterol after myocardial infarction, several clinical and
      demographic subgroups were less likely to receive cholesterol-lowering therapy,
      and many patients were unaware of their cholesterol level. Health-care providers
      and managed-care plans can use these findings to promote cholesterol testing and
      treatment for patients with coronary heart disease who are most likely to benefit
      from these efforts.

PMID- 11841526
TI  - Barriers to screening for domestic violence.
AB  - CONTEXT: Domestic violence has an estimated 30% lifetime prevalence among women,
      yet physicians detect as few as 1 in 20 victims of abuse. OBJECTIVE: To identify
      factors associated with physicians' low screening rates for domestic violence and
      perceived barriers to screening. DESIGN: Cross-sectional postal survey.
      PARTICIPANTS: A national systematic sample of 2,400 physicians in 4 specialties
      likely to initially encounter abused women. The overall response rate was 53%.
      MAIN OUTCOME MEASURE: Self-reported percentage of female patients screened for
      domestic violence; logistic models identified factors associated with screening
      less than 10%. RESULTS: Respondent physicians screened a median of only 10%
      (interquartile range, 2 to 25) of female patients. Ten percent reported they
      never screen for domestic violence; only 6% screen all their patients. Higher
      screening rates were associated with obstetrics-gynecology specialty (odds ratio
      [OR], 0.49; 95% confidence interval [CI], 0.31 to 0.78), female gender (OR, 0.51;
      CI, 0.35 to 0.73), estimated prevalence of domestic violence in the physician's
      practice (per 10%, OR, 0.72; CI, 0.65 to 0.80), domestic violence training in the
      last 12 months (OR, 0.46; CI, 0.29 to 0.74) or previously (OR, 0.54; CI, 0.34 to
      0.85), and confidence in one's ability to recognize victims (per Likert-scale
      point, OR, 0.71; CI, 0.58 to 0.87). Lower screening rates were associated with
      emergency medicine specialty (OR, 1.72; CI, 1.13 to 2.63), agreement that
      patients would volunteer a history of abuse (per Likert-scale point, OR, 1.60;
      CI, 1.25 to 2.05), and forgetting to ask about domestic violence (OR, 1.69; CI,
      1.42 to 2.02). CONCLUSIONS: Physicians screen few female patients for domestic
      violence. Further study should address whether domestic violence training can
      correct misperceptions and improve physician self-confidence in caring for
      victims and whether the use of specific intervention strategies can enhance
      screening rates.

PMID- 11841525
TI  - Barriers to initiating depression treatment in primary care practice.
AB  - OBJECTIVE AND DESIGN: This study used qualitative and quantitative methods to
      examine the reasons primary care physicians and nurses offered for their
      inability to initiate guideline-concordant acute-phase care for patients with
      current major depression. PARTICIPANTS AND SETTING: Two hundred thirty-nine
      patients with 5 or more symptoms of depression seeing 12 physicians in 6 primary
      care practices were randomized to the intervention arm of a trial of the
      effectiveness of depression treatment. Sixty-six (27.6%) patients identified as
      failing to meet criteria for guideline-concordant treatment 8 weeks following the
      index visit were the focus of this analysis. METHODS: The research team
      interviewed the 12 physicians and 6 nurse care managers to explore the major
      reasons depressed patients fail to receive guideline-concordant acute-phase care.
      This information was used to develop a checklist of barriers to depression care.
      The 12 physicians then completed the checklist for each of the 64 patients for
      whom he or she was the primary care provider. Physicians chose which barriers
      they felt applied to each patient and weighted the importance of the barrier by
      assigning a total of 100 points for each patient. Cluster analysis of barrier
      scores identified naturally occurring groups of patients with common barrier
      profiles. RESULTS: The cluster analysis produced a 5-cluster solution with
      profiles characterized by patient resistance (19 patients, 30.6%), patient
      noncompliance with visits (15 patients, 24.2%), physician judgment overruled the
      guideline (12 patients, 19.3%), patient psychosocial burden (8 patients, 12.9%),
      and health care system problems (8 patients, 12.9%). The physicians assigned
      4,707 (75.9%) of the 6,200 weighting points to patient-centered barriers.
      Physician-centered barriers accounted for 927 (15.0%) and system barriers
      accounted for 566 (9.1%) of weighting points. Twenty-eight percent of the
      patients not initiating guideline-concordant acute-stage care went on to receive
      additional care and met criteria for remission at 6 months, with no statistical
      difference across the 5 patient clusters. CONCLUSIONS: Current interventions fail
      to address barriers to initiating guideline-concordant acute-stage care faced by
      more than a quarter of depressed primary care patients. Physicians feel that
      barriers arise most frequently from factors centered with the patients, their
      psychosocial circumstances, and their attitudes and beliefs about depression and
      its care. Physicians less frequently make judgments that overrule the guidelines,
      but do so when patients have complex illness patterns. Further descriptive and
      experimental studies are needed to confirm and further examine barriers to
      depression care. Because few untreated patients improve without acute-stage care,
      additional work is also needed to develop new intervention components that
      address these barriers.

PMID- 11841527
TI  - The Voices of survivors documentary: using patient narrative to educate
      physicians about domestic violence.
AB  - This article describes a method of developing physician education materials using
      analysis of domestic violence patient experiences and patients' descriptions of
      their experiences. The process began with interviews of 21 domestic violence
      survivors, focusing on what they wanted to teach physicians. Qualitative analysis
      of these interviews identified 4 main themes regarding what survivors wanted
      physicians to understand about life in an abusive relationship: that domestic
      violence is universal, that it is more than just physical assaults, that it is
      all about power and control, and that it affects the entire family. Because what
      survivors wanted from physicians differed depending on where they were in their
      abusive relationships, recommendations were developed for each of 5 common
      situations: when a patient may not yet recognize the abuse, when s/he may not be
      ready or able to disclose the abuse, when s/he chooses to remain in an abusive
      relationship, when s/he is seeking care for an acute assault, and when s/he has
      left the relationship but not yet healed. Interview excerpts representing each of
      the identified themes are used to create a 30-minute educational documentary. A
      written companion guide covers the traditional aspects of domestic violence
      education. In teaching about domestic violence or other health problems where it
      is difficult for physicians to understand their patients intuitively, an
      educator's most important role may be to direct learners to listen to the
      experience and wisdom of patients.

PMID- 11841528
TI  - Insurance benefit preferences of the low-income uninsured.
AB  - OBJECTIVE: A frequently cited obstacle to universal insurance is the lack of
      consensus about what benefits to offer in an affordable insurance package. This
      study was conducted to assess the feasibility of providing uninsured patients the
      opportunity to define their own benefit package within cost constraints. DESIGN:
      Structured group exercises. SETTING: Community setting. PARTICIPANTS: Uninsured
      individuals recruited from clinical and community settings in central North
      Carolina. MEASUREMENTS: Insurance choices were measured using a simulation
      exercise, CHAT (Choosing Healthplans All Together). Participants designed managed
      care plans, individually and as groups, by selecting from 15 service categories
      having varied levels of restriction (e.g., formulary, copayments) within the
      constraints of a fixed monthly premium comparable to the typical per member/per
      month managed care premium paid by U.S. employers. MAIN RESULTS: Two hundred
      thirty-four individuals who were predominantly male (70%), African American
      (55%), and socioeconomically disadvantaged (53% earned <$15,000 annually)
      participated in 22 groups and were able to design health benefit packages
      individually and in groups. All 22 groups chose to cover hospitalization,
      pharmacy, dental, and specialty care, and 21 groups chose primary care and mental
      health. Although individuals' choices differed from their groups' selections, 86%
      of participants were willing to abide by group choices. CONCLUSIONS: Groups of
      low-income uninsured individuals are able to identify acceptable benefit packages
      that are comparable in cost but differ in benefit design from managed care
      contracts offered to many U.S. employees today.

PMID- 11841529
TI  - Risk factors for hepatitis C virus infection among homeless adults.
AB  - OBJECTIVE: To describe the prevalence of hepatitis C virus (HCV) infection in a
      sample of homeless and impoverished adults and examine risk factors for HCV
      infection in the overall sample and as a function of injection drug use. DESIGN:
      Assays were conducted on stored sera. Sociodemographic characteristics and risky
      sexual activity were measured by content-specific items. Substance use was
      measured by a structured questionnaire. HCV antibodies were tested by enzyme
      linked immunosorbent assay; a confirmatory level was defined by recombinant
      immunoblot assay. SETTINGS: Shelters ( N = 36) and outdoor locations in Los
      Angeles. PARTICIPANTS: Eight hundred eighty-four homeless women and/or partners
      or friends. RESULTS: Among this sample of 884 homeless and impoverished adults,
      22% were found to be HCV infected. Lifetime injection drug users (IDUs) (cocaine,
      crack, and methamphetamine) and recent daily users of crack were more likely than
      nonusers or less-frequent users of these drugs to be HCV-infected. Similar
      results were found for those who had been hospitalized for a mental health
      problem. Among non-injection drug users and persons in the total sample, those
      who reported lifetime alcohol abuse were more likely than those who did not to be
      HCV infected. Controlling for sociodemographic characteristics, multiple logistic
      regression analyses revealed IDUs have over 25 times greater odds of having HCV
      infection than non-IDUs. HCV infection was also predicted by older age, having
      started living on one's own before the age of 18, and recent chronic alcohol use.
      Males and recent crack users had about one and a half times greater odds of HCV
      infection when compared to females and non-chronic crack users. CONCLUSIONS:
      Targeted outreach for homeless women and their partners, including HCV testing
      coupled with referrals to HCV and substance abuse treatments, may be helpful.

PMID- 11841532
TI  - Antibiotic prescribing: can we make it easier?

PMID- 11841530
TI  - Adherence of low-income women to cancer screening recommendations.
AB  - BACKGROUND: African-American and low-income women have lower rates of cancer
      screening and higher rates of late-stage disease than do their counterparts.
      OBJECTIVE: To examine the effects of primary care, health insurance, and HMO
      participation on adherence to regular breast, cervical, and colorectal cancer
      screening. DESIGN: Random-digit-dial and targeted household telephone survey of a
      population-based sample. SETTING: Washington, D.C. census tracts with > or =30%
      of households below 200% of federal poverty threshold. PARTICIPANTS: Included in
      the survey were 1,205 women over age 40, 82% of whom were African American. MAIN
      OUTCOME MEASURES: Adherence was defined as reported receipt of the last 2
      screening tests within recommended intervals for age. RESULTS: The survey
      completion rate was 85%. Overall, 75% of respondents were adherent to regular Pap
      smears, 66% to clinical breast exams, 65% to mammography, and 29% to fecal occult
      blood test recommendations. Continuity with a single primary care practitioner,
      comprehensive service delivery, and higher patient satisfaction with the
      relationships with primary care practitioners were associated with higher
      adherence across the 4 screening tests, after considering other factors.
      Coordination of care also was associated with screening adherence for women age
      65 and over, but not for the younger women. Compared with counterparts in non-HMO
      plans, women enrolled in health maintenance organizations were also more likely
      to be adherent to regular screening (e.g., Pap, odds ratio [OR] 1.89, 95%
      confidence interval [CI] 1.11 to 3.17; clinical breast exam, OR 2.04, 95% CI 1.21
      to 3.44; mammogram, OR 1.95, 95% CI 1.15 to 3.31; fecal occult blood test, OR
      1.70, 95% CI 1.01 to 2.83.) CONCLUSIONS: Organizing healthcare services to
      promote continuity with a specific primary care clinician, a comprehensive array
      of services available at the primary care delivery site, coordination among
      providers, and better patient-practitioner relationships are likely to improve
      inner-city, low-income women's adherence to cancer screening recommendations.

PMID- 11841531
TI  - Influence of body weight on patients' satisfaction with ambulatory care.
AB  - Patients with obesity experience psychosocial consequences because of their
      weight and report physician bias. We examined whether obesity is associated with
      lower patient satisfaction with ambulatory care among 2,858 patients seen at 11
      academically affiliated primary care practices in Boston. Compared with normal
      weight patients (body mass index [BMI], 19.0 to 24.9 kg/M 2), overweight (BMI,
      25.0 to 29.9 kg/M 2) and obese patients (BMI > or =30 kg/M 2) reported lower
      overall satisfaction scores at their most recent visit; the scores were 85.5,
      85.0, and 82.6 out a possible 100, respectively (P =.05). After adjustment for
      potential confounders including illness burden, obese patients reported lower
      scores but the difference was not statistically significant (mean difference,
      1.23 [95% confidence interval -0.67 to 3.12]). Patient satisfaction with their
      usual provider and their practice did not vary by BMI group. Obesity is
      associated with only modest decreases in satisfaction scores with the most recent
      visit, which were explained largely by higher illness burden among obese
      patients.

PMID- 11841533
TI  - Domestic violence and clinical medicine: learning from our patients and from our
      fears.

PMID- 11841535
TI  - Transforming growth factor-beta signaling through the Smad pathway: role in
      extracellular matrix gene expression and regulation.
AB  - Transforming growth factor (TGF)-beta represents a prototype of multifunctional
      cytokine. Its broad activities include, among others, context-specific inhibition
      or stimulation of cell proliferation, control of extracellular matrix (ECM)
      synthesis and degradation, control of mesenchymal-epithelial interactions during
      embryogenesis, mediation of cell and tissue responses to injury, control of
      carcinogenesis, and modulation of immune functions. Regulation of production and
      turnover of ECM components is essential for tissue homeostasis and function. TGF
      beta exerts its effects on cell proliferation, differentiation, and migration in
      part through its capacity to modulate the deposition of ECM components.
      Specifically, TGF-beta isoforms have the ability to induce the expression of ECM
      proteins in mesenchymal cells, and to stimulate the production of protease
      inhibitors that prevent enzymatic breakdown of the ECM. Deregulation of these
      functions is associated with abnormal connective tissue deposition, as observed,
      for example, during scarring or fibrotic processes. In this review we discuss the
      current understanding of the signaling mechanisms used by TGF-beta to elicit its
      effects on target genes, focusing primarily on Smad proteins and their role in
      the transcriptional regulation of ECM gene expression. Other signaling
      mechanisms, such as the MAP/SAP kinase or Ras pathways, although potentially
      important for transmission of some of the TGF-beta signals, will not be
      described. Transforming growth factor-beta (TGF-beta) plays a critical role in
      the regulation of extracellular matrix gene expression. Its overexpression is
      believed to contribute to the development of tissue fibrosis. The recent
      identification of Smad proteins, TGF-beta receptor kinase substrates that
      translocate into the cell nucleus to act as transcription factors, has increased
      our understanding of the molecular mechanisms underlying TGF-beta action. This
      review focuses primarily on the mechanisms underlying Smad modulation of gene
      expression and how they relate to wound healing. Potential implications for the
      development of therapeutic approaches against tissue fibrosis are discussed.

PMID- 11841536
TI  - Molecular mechanisms regulating hair follicle development.
AB  - Clinical conditions causing hair loss, such as androgenetic alopecia, alopecia
      areata, and scarring alopecia, can be psychologically devastating to individuals
      and are the target of a multimillion dollar pharmaceutical industry. The
      importance of the hair follicle in skin biology, however, does not rest solely
      with its ability to produce hair. Hair follicles are self-renewing and contain
      reservoirs of multipotent stem cells that are capable of regenerating the
      epidermis and are thought to be utilized in wound healing. Hair follicles are
      also the sites of origin of many neoplasias, including some basal cell carcinomas
      and pilomatricoma. These diseases result from inappropriate activation of
      signaling pathways that regulate hair follicle morphogenesis. Identification of
      the signaling molecules and pathways operating in developing and postnatal,
      cycling, hair follicles is therefore vital to our understanding of pathogenic
      states in the skin and may ultimately permit the development of novel therapies
      for skin tumors as well as for hair loss disease. The purpose of this review is
      to summarize recent progress in our understanding of the molecular mechanisms
      regulating hair follicle formation, and to discuss ways in which this information
      may eventually be utilized in the clinic.

PMID- 11841537
TI  - hKAP1.6 and hKAP1.7, two novel human high sulfur keratin-associated proteins are
      expressed in the hair follicle cortex.
AB  - Hair fiber differentiation involves the expression of both hair keratin
      intermediate filament proteins and their associated proteins, termed keratin
      associated proteins. In this study, cDNA clones encoding two novel keratin
      associated proteins were isolated from human hair follicle mRNA. The predicted
      amino acid sequence derived from these clones revealed that these proteins
      represent members of the human keratin-associated protein 1 family. They show
      strong sequence homology to two previously described keratin-associated protein 1
      family members hKAP1.1 A and hKAP1.1B. We have called these new proteins hKAP1.6
      and hKAP1.7, respectively. RNA in situ hybridization studies of human anagen hair
      follicles using a conserved probe for these four keratin-associated protein 1
      members demonstrated the expression of this group in the differentiated portions
      of the hair cortex.

PMID- 11841538
TI  - Compound heterozygosity for non-sense and mis-sense mutations in desmoplakin
      underlies skin fragility/woolly hair syndrome.
AB  - The constitutive desmosomal plaque protein desmoplakin plays a vital part in
      keratinocyte adhesion in linking the transmembranous desmosomal cadherins to the
      cytoplasmic keratin filament network. Recently, mutations in desmoplakin have
      been shown to underlie some cases of the autosomal dominant disorder, striate
      palmoplantar keratoderma, as well as an autosomal recessive condition
      characterized by dilated cardiomyopathy, woolly hair, and keratoderma. Here, we
      describe two unrelated individuals with a new autosomal recessive genodermatosis
      characterized by focal and diffuse palmoplantar keratoderma, hyperkeratotic
      plaques on the trunk and limbs, varying degrees of alopecia, but no apparent
      cardiac anomalies. Mutation screening of desmoplakin demonstrated compound
      heterozygosity for a non-sense/mis-sense combination of mutations in both cases,
      C809X/N287K and Q664X/R2366C, respectively. Heterozygous carriers of any of these
      mutations displayed no phenotypic abnormalities. Immunohistochemistry of skin
      biopsies from both affected individuals revealed that desmoplakin was not just
      located at the cell periphery but there was also cytoplasmic staining. In
      addition, electron microscopy demonstrated acantholysis throughout all layers of
      the skin, focal detachment of desmosomes into the intercellular spaces, and
      perinuclear condensation of the suprabasal keratin intermediate filament network.
      Clinicopathologic and mutational analyses therefore demonstrate that desmoplakin
      haploinsufficiency can be tolerated in some cases, but that in combination with a
      mis-sense mutation on the other allele, the consequences are a severe
      genodermatosis with specific clinical manifestations.

PMID- 11841539
TI  - PpIX fluorescence kinetics and increased skin damage after intracutaneous
      injection of 5-aminolevulinic acid and repeated illumination.
AB  - Photodynamic therapy with topically applied 5-aminolevulinic acid is used
      successfully for superficial skin lesions. The results for thicker, nodular
      lesions are less favorable. The method of aminolevulinic acid administration, the
      concentrations of aminolevulinic acid, and the irradiation schemes used so far
      have not been investigated thoroughly. As aminolevulinic acid photodynamic
      therapy has high potential for the increasing problem of skin cancer, we
      investigated both visually and histopathologically the photodynamic-therapy
      induced skin damage after intracutaneous administration of aminolevulinic acid in
      normal porcine skin. We also investigated the kinetics of the aminolevulinic-acid
      induced photosensitizer protoporphyrin IX fluorescence after irradiation in
      relation to fluence and irradiance. Finally we investigated the effect on
      photodynamic-therapy-induced damage of a fractionated irradiation. This study
      demonstrates that intracutaneous administration of aminolevulinic acid leads to
      higher fluorescence levels and thus to formation of higher protoporphyrin IX
      concentrations than topical application of aminolevulinic acid cream. The peak
      level of protoporphyrin IX after intracutaneous administration of aminolevulinic
      acid is reached earlier than after topical administration. The comeback of
      fluorescence, indicating re-synthesis of protoporphyrin IX after irradiation, is
      inhibited with increasing fluence. Photodynamic-therapy-induced damage increases
      with increasing fluence, but is independent of the irradiance. Finally, the
      photodynamic-therapy-induced skin damage seems to be greater after fractionated
      irradiations with two equal light fractions of 15 J per cm2 separated by a dark
      interval of 2 h.

PMID- 11841540
TI  - Role of zyxin in differential cell spreading and proliferation of melanoma cells
      and melanocytes.
AB  - Cell spreading, proliferation, and survival are modulated by focal adhesions
      linking extracellular matrix proteins, integrins, and the cytoskeleton. Zyxin is
      a focal-adhesion-associated phosphoprotein with one domain involved in the
      control of actin assembly and three protein-protein adapter domains implicated in
      the regulation of cell growth and differentiation. We characterized zyxin
      expression in normal human melanocytes and six melanoma cell lines in relation to
      cell spreading, growth, and differentiation using Western immunoblotting
      techniques, image analysis, flow cytometry, and confocal microscopy. We found
      that zyxin, focal adhesion kinase, and paxillin were significantly upregulated in
      melanoma cells compared to melanocytes. Zyxin expression directly related to cell
      spreading and proliferation and inversely related to differentiation, whereas
      focal adhesion kinase correlated only to cell spreading and paxillin did not
      significantly correlate with any of the parameters. Treatment of melanoma cells
      with 12-O-tetradecanoylphorbol-13-acetate downregulated zyxin expression,
      inhibited cell spreading and proliferation, and promoted differentiation. In
      contrast, 12-O-tetradecanoylphorbol-13-acetate, a mitogen for melanocytes,
      induced upregulation of zyxin expression in melanocytes. These findings are
      consistent with a role of zyxin in modulation of cell spreading, proliferation,
      and differentiation. Therapies directed at the downregulation of this focal
      adhesion phosphoprotein in melanoma cells implicate a new approach for
      controlling melanoma cell growth.

PMID- 11841541
TI  - Histamine is involved in ultraviolet B-induced pigmentation of guinea pig skin.
AB  - We previously reported that histamine induced melanogenesis in cultured human
      melanocytes and that the stimulatory effect was mediated by protein kinase A
      activation via H2 receptors. It is well-known that ultraviolet B irradiation
      causes acute inflammation, known as erythema, and subsequent pigmentation, and
      there are several reports demonstrating an elevation of the histamine levels in
      ultraviolet B-irradiated skin. Thus, to evaluate the involvement of histamine in
      ultraviolet B-induced skin pigmentation, we examined the effect of an H2
      antagonist in brownish guinea pig skin. Daily exposure to 200 mJ per cm2
      ultraviolet B for 3 d evoked erythema and subsequent pigmentation in the skin
      samples tested. Moreover, a remarkable increase in dopa-positive melanocytes was
      observed in the pigmented area, which showed an increase in melanin synthesis.
      Topical application of famotidine, an H2 antagonist, significantly reduced
      pigmentation and moderated the increase of dopa-positive melanocytes in the
      ultraviolet B-irradiated skin. Even when the initiation of famotidine application
      was delayed to day 2 after irradiation, an inhibitory activity on ultraviolet B
      induced pigmentation was observed; however, the ultraviolet B-induced erythema
      was not suppressed by topically applied famotidine. Thus, we concluded that
      histamine is involved in ultraviolet B-induced pigmentation and that famotidine
      suppressed the pigmentation by the prevention of histamine binding to H2
      receptors in melanocytes but not by prevention of ultraviolet B permeability and
      inflammation.

PMID- 11841542
TI  - DCIR acts as an inhibitory receptor depending on its immunoreceptor tyrosine
      based inhibitory motif.
AB  - Major histocompatibility complex class II positive cells, namely dendritic cells,
      monocytes/macrophages, and B cells, are categorized as antigen-presenting cells.
      Dendritic cells, so-called professional antigen-presenting cells, use distinct
      sets of surface receptors before and after maturation: those to capture antigens
      and those to interact with T cells, respectively. But there remain many surface
      molecules whose functions are still unknown. In this study, we isolated dendritic
      cell immunoreceptor from mouse bone-marrow-derived mature dendritic cells.
      Dendritic cell immunoreceptor is a recently reported C-type lectin receptor
      characteristic with cytoplasmic immunoreceptor tyrosine-based inhibitory motif.
      Expression of mouse dendritic cell immunoreceptor mRNA was observed specifically
      in spleen and lymph node, slightly increased with dendritic cell maturation
      during in vitro culture of bone marrow cells, and was not detected in cultured
      natural killer cells. Surface expression of mouse dendritic cell immunoreceptor
      protein was observed in splenic antigen-presenting cells including B cells,
      monocytes/macrophages, and dendritic cells, but not in T cells. To reveal the
      downregulating capacity of dendritic cell immunoreceptor in antigen-presenting
      cells, the change of B-cell-receptor-mediated signals after coligation with a
      chimeric Fcgamma receptor IIB containing the cytoplasmic portion of mouse
      dendritic cell immunoreceptor was examined. As a result, we detected two distinct
      inhibitory effects of cytoplasmic dendritic cell immunoreceptor minus sign
      inhibition of B-cell-receptor-mediated Ca2+ mobilization and protein tyrosine
      phosphorylation minus sign and both of these effects required the tyrosine
      residue inside the immunoreceptor tyrosine-based inhibitory motif. This report
      presents immunoreceptor tyrosine-based inhibitory motif-dependent negative
      regulatory function of dendritic cell immunoreceptors. In conclusion, mouse
      dendritic cell immunoreceptor expressed on antigen-presenting cells can exert two
      distinct inhibitory signals depending on its immunoreceptor tyrosine-based
      inhibitory motif tyrosine residue.

PMID- 11841543
TI  - Type XVI collagen is expressed in factor XIIIa+ monocyte-derived dermal
      dendrocytes and constitutes a potential substrate for factor XIIIa.
AB  - We have previously reported that connective tissue cells in the superficial
      dermis preferentially express alpha1(XVI) collagen rather than those in the lower
      dermis. Double immunofluorescence labeling using the antibodies for alpha1(XVI)
      collagen and factor XIIIa (plasma transglutaminase), which is a marker of dermal
      dendrocytes, demonstrated that both antibodies reacted with the same cells in the
      superficial dermis of normal skin as well as the lesional skins of dermal
      dendrocyte-related disorders, dermatofibroma, and psoriasis. Dermal dendrocytes
      are considered to be established by a culture of peripheral blood monocytes in
      the presence of granulocyte macrophage-colony stimulating factor and interleukin
      4. Reverse transcription--polymerase chain reaction, metabolic labeling, and
      immunofluorescence studies demonstrated that treatment of CD14+ peripheral blood
      monocytes with granulocyte macrophage-colony stimulating factor/interleukin-4
      over a period of 8 d resulted in the induction of alpha1(XVI) collagen as well as
      factor XIIIa. The physiologic significance of colocalization of alpha1(XVI)
      collagen and factor XIIIa in the tissue and their coordinate induction in CD14+
      monocyte-derived dendritic cells in vitro was studied. Considerable incorporation
      of [3H]putrescine by factor XIIIa into recombinant noncollagenous domain (NC) 11
      but not into collagenous domain (COL) 1.NC1 domain of the alpha1(XVI) polypeptide
      was found. Incubation of recombinant NC11 of alpha1(XVI) polypeptide with factor
      XIIIa in vitro produced a covalent cross-linking complex on sodium dodecylsulfate
      polyacrylamide gel electrophoresis. The results indicate that alpha1(XVI)
      collagen is constitutively expressed by most dermal dendrocytes in the skin and
      dendritic cells differentiated from peripheral blood monocytes in vitro. Type XVI
      collagen is expressed in factor XIIIa+ dermal dendrocytes and may form an
      intermolecular cross-linking through NC11 domain by the reaction catalyzed by
      factor XIIIa contributing to the structural integrity of factor XIIIa+ dendritic
      cell-rich tissues.

PMID- 11841544
TI  - Human beta-defensin-2 production in keratinocytes is regulated by interleukin-1,
      bacteria, and the state of differentiation.
AB  - Intact human epidermis resists invasion by pathogenic microbes but the
      biochemical basis of its resistance is not well understood. Recently, an
      antimicrobial peptide, human beta-defensin-2, was discovered in inflamed
      epidermis. We used a recombinant baculovirus/insect cell system to produce human
      beta-defensin-2 and confirmed that at micromolar concentrations it has a broad
      spectrum of antimicrobial activity, with the striking exception of Staphylococcus
      aureus. Immunostaining with a polyclonal antibody to human beta-defensin-2 showed
      that the expression of human beta-defensin-2 peptide by human keratinocytes
      required differentiation of the cells (either by increased calcium concentration
      or by growth and maturation in epidermal organotypic culture) as well as a
      cytokine or bacterial stimulus. Interleukin-1alpha, interleukin-1beta, or live
      Pseudomonas aeruginosa proved to be the most effective stimuli whereas other
      bacteria and cytokines had little or no ability to induce human beta-defensin-2
      synthesis. In interleukin-1alpha-stimulated epidermal cultures, human beta
      defensin-2 first appeared in the cytoplasm in differentiated suprabasal layers of
      skin, next in a more peripheral web-like distribution in the upper layers of the
      epidermis, and then over a few days migrated to the stratum corneum. By
      semiquantitative Western blot analysis of epidermal lysates, the average
      concentration of human beta-defensin-2 in stimulated organotypic epidermal
      culture reached 15--70 microg per gram of tissue, i.e., 3.5-16 microM, well
      within the range required for antimicrobial activity. Because of the restricted
      pattern of human beta-defensin-2 distribution in the epidermis, its local
      concentration must be much higher. Defensins and other antimicrobial peptides of
      inflamed epidermis are likely to play an important antimicrobial role in host
      defense against cutaneous pathogens.

PMID- 11841545
TI  - Sequential reorganization of cornified cell keratin filaments involving filaggrin
      mediated compaction and keratin 1 deimination.
AB  - The final step of keratinocyte differentiation, transition from the granular
      cells to the cornified cells, involves various post-translational modifications
      that include deimination of arginine residues. Major deiminated epidermal
      proteins are derived from K1. Two preferred deimination sites were identified in
      mouse K1, one in the V1 and the other in the V2 subdomains. An antibody against
      the deiminated peptide sequence in the V2 subdomain recognized not only
      deiminated mouse K1 but also deiminated human K1. In this study we analyzed
      distribution of deiminated K1 in normal human skin and in bullous congenital
      ichthyosiform erythroderma at light and electron microscopic levels. In normal
      skin the first few (1-3) cornified cell layers were positive for filaggrin and
      negative for the antibody against deiminated mouse K1 peptide, whereas the more
      superficial cells were negative for filaggrin and strongly positive for the
      antibody against deiminated mouse K1 peptide, indicating slightly delayed onset
      of K1 deimination at the initial stage of cornification. The clumped keratin in
      bullous congenital ichthyosiform erythroderma that was not properly compacted
      with filaggrin was poorly positive to the antibody against deiminated mouse K1
      peptide. In addition, K1 derivatives in bullous congenital ichthyosiform
      erythroderma reacted poorly with the antibody against deiminated mouse K1 peptide
      compared with the normal control in immunoblot analyses. Our results suggest
      sequential reorganization of cornified cell keratin filaments involving filaggrin
      mediated compaction and K1 deimination. Abnormal keratin aggregation in bullous
      congenital ichthyosiform erythroderma is likely to disturb the normal deimination
      of K1.

PMID- 11841546
TI  - Skin as a potential organ for ectopic monoclonal antibody production.
AB  - The therapeutic potential of monoclonal antibodies for treating a variety of
      severe or life-threatening diseases is high. Although intravenous infusion
      appears the simplest and most obvious mode of administration, it is not
      applicable to many long-term treatments. It might be advantageously replaced by
      gene/cell therapies, however, rendering treatments cost-effective and eliminating
      the short- and long-term side-effects associated with injection of massive doses
      of antibodies. We have tested whether skin can potentially be used as an organ
      for production and systemic delivery of ectopic antibodies. Normal human primary
      keratinocytes were shown to be capable of synthesis and secretion of a model
      monoclonal antibody directed against human thyroglobulin upon retroviral gene
      transduction in vitro. Neo- epidermis reconstructed in vitro, either in cell
      culture inserts or on dermal substrates, from such modified keratinocytes also
      produced the monoclonal antibody. Interestingly, the latter could cross the
      epidermis basal layer and be released in culture fluids. Finally, grafting of
      epidermis reconstituted in vitro on dermal substrates to SCID mice permitted
      sustained monoclonal antibody delivery into the bloodstream to be achieved. Our
      data thus show that genetically engineered keratinocytes can potentially be used
      for genetic antibody-based immunotherapies. They also indicate that proteins as
      big as 150 kDa, after release by engineered keratinocytes into skin intercellular
      spaces, can migrate to the general circulation, which is potentially important
      for a number of other gene-based therapies.

PMID- 11841547
TI  - Non-invasive method for quantitative evaluation of exogenous compound deposition
      on skin.
AB  - Topical application of active compounds on skin is common to both pharmaceutical
      and cosmetic industries. Quantification of the concentration of a compound
      deposited on the skin is important in determining the optimum formulation to
      deliver the pharmaceutical or cosmetic benefit. The most commonly used techniques
      to date are either invasive or not easily reproducible. In this study, we have
      developed a noninvasive alternative to these techniques based on
      spectrofluorimetry. A mathematical model based on diffusion approximation theory
      is utilized to correct fluorescence measurements for the attenuation caused by
      endogenous skin chromophore absorption. The limitation is that the compound of
      interest has to be either fluorescent itself or fluorescently labeled. We used
      the method to detect topically applied salicylic acid. Based on the mathematical
      model a calibration curve was constructed that is independent of endogenous
      chromophore concentration. We utilized the method to localize salicylic acid in
      epidermis and to follow its dynamics over a period of 3 d.

PMID- 11841548
TI  - Role of the nude gene in epithelial terminal differentiation.
AB  - Loss-of-function mutations in Whn (Hfh11, Foxn1), a winged-helix/forkhead
      transcription factor, cause the nude phenotype, which is characterized by the
      abnormal morphogenesis of the epidermis, hair follicles, and thymus. To delineate
      the biochemical pathway of Whn, we investigated its upstream regulation and
      downstream effects using primary keratinocytes from wild-type and transgenic
      mice. The transgenic animals express whn from the involucrin promoter, which is
      active in keratinocytes undergoing terminal differentiation. In wild-type
      cultures, as in the epidermis, Whn was induced during the early stages of
      terminal differentiation and declined during later stages. In transgenic
      keratinocytes, whn overexpression altered the terminal differentiation program,
      stimulating an early differentiation marker (keratin 1) and suppressing later
      markers (profilaggrin, loricrin, and involucrin). These results suggest a role
      for Whn in the stepwise or temporal regulation of differentiation, as Whn can
      ensure that the differentiation program is carried out in proper sequence. Before
      the start of differentiation, Whn levels were suppressed by the p42/p44 mitogen
      activated protein kinase cascade, and this signaling pathway was rapidly
      inactivated as differentiation began. Thus, as keratinocytes commit to terminal
      differentiation, mitogen-activated protein kinase signaling decreases, which
      permits the induction of Whn; Whn then activates early features of the
      differentiation program.

PMID- 11841549
TI  - Gas chromatography/mass spectrometry characterization of corticosteroid
      metabolism in human immortalized keratinocytes.
AB  - To continue our studies on the cutaneous expression of a
      proopiomelanocortin/corticotropin-releasing hormone system, we investigated
      whether this is accompanied by adrenal-type enzymatic activity. Immortalized
      cultured human keratinocytes were incubated with radiolabeled corticosteroids.
      Analysis by thin-layer chromatography showed rapid transformation of both
      progesterone and deoxycorticosterone; one of the progesterone metabolites
      migrated at the same rate as deoxycorticosterone. Gas chromatography/mass
      spectrometry further identified as major species of deoxycorticosterone
      metabolites 3beta,6alpha,21-trihydroxy-5alpha-pregnan-20-one, 3alpha,6alpha,21
      trihydroxy-5alpha-pregnan-20-one, and 3alpha5alpha- and 3beta5alpha
      tetrahydrodeoxycorticosterone. Minor metabolites were 3alpha,21-dihydroxy-5
      pregnen-20- one (3alphaDelta5-21-OHpregnenolone), 3beta,21-dihydroxy-5-pregnen-20
      one (3betaDelta5-21-OHpregnenolone), 3alpha,21-dihydroxy-4-pregnen-20-one
      (3alphaDelta4-21-OHpregnenolone), 6-hydroxy-dihydrodeoxycorticosterone, and two 5
      dihydrodeoxycorticosterone species. Thus, in addition to sex steroids
      keratinocytes also actively metabolize corticosteroids along similar enzymatic
      pathways. The surprising detection of 3alphaDelta5-21-OHpregnenolone and 3
      betaDelta5-21-OHpregnenolone, indicating Delta4-ketosteroids to Delta5
      hydroxysteroids conversion, provides strong evidence for the occurrence, at least
      in human keratinocytes, of isomerase activity that allows the reaction to proceed
      in reverse of its usual direction. As skin expresses 3alpha/beta-hydroxysteroid
      dehydrogenase/Delta5-Delta4 isomerases, cutaneous reactions catalyzed by these
      enzymes must be reversible. In conclusion, besides elements of the corticotropin
      releasing hormone/proopiomelanocortin system human keratinocytes show high levels
      of corticosteroid metabolizing activity. Moreover, the wide array of steroid
      products generated from a single substrate indicates serial progressive
      conversion involving 5alpha-reductase, 6alpha-hydroxylase, 3alpha/beta
      hydroxysteroid dehydrogenase, and reverse Delta4minus signDelta5 isomerase
      enzymes. As distinct from the adrenal cortex, production of A, B, Aldo,
      18OHdeoxycorticosterone, or F in keratinocytes was absent or below limits of
      detectability.

PMID- 11841550
TI  - Mitogen- and ultraviolet-B-induced signaling pathways in normal human
      melanocytes.
AB  - In normal human melanocytes various mitogens activate the mitogen-activated
      protein kinases ERK1/2 and the downstream transcription factor CREB (Ca2+/cAMP
      response element binding protein). Endothelin-1, basic fibroblast growth factor,
      and alpha-melanotropin interact synergistically to stimulate human melanocyte
      proliferation. The former two mitogens phosphorylated ERK1/2, its substrate
      p90rsk, and CREB. Alpha-melanotropin, forskolin, or dibutyryl cAMP failed to
      phosphorylate any of those targets, however. The concomitant presence of
      endothelin-1, basic fibroblast growth factor, and alpha-melanotropin
      significantly potentiated CREB phosphorylation. The mitogen-induced
      phosphorylation of p90rsk and CREB was dependent on ERK1/2 activation, and was
      mediated by intracellular calcium mobilization and by protein kinase C and
      tyrosine kinase activation, but not by activation of the cAMP-dependent protein
      kinase A. Exposure of melanocytes to ultraviolet radiation B resulted in the
      phosphorylation of the stress-induced mitogen- activated protein kinases p38 and
      JNK/SAPK, but not ERK1/2. Ultraviolet radiation B induced the phosphorylation of
      CREB via a pathway that was partially dependent on p38, but had no effect on
      p90rsk or ERK1/2. Therefore, in human melanocytes, CREB is a common downstream
      target for distinct effectors that are involved in either mitogenic signaling or
      stress signaling initiated by ultraviolet radiation B.

PMID- 11841551
TI  - Especially polymorphonuclear leukocytes, but also monomorphonuclear leukocytes,
      roll spontaneously in venules of intact rat skin: involvement of E-selectin.
AB  - White blood cells roll spontaneously in venules of intact, noninflamed rat skin.
      We investigated noninvasively in two experimental series which leukocyte subtypes
      participate in this phenomenon and the possible involvement of E-selectin. Male
      Lewis rats were anesthetized with sodium pentobarbital, and intravital video
      microscopy was performed on postcapillary venules in the nail-fold of a hind leg.
      In series 1 acridine yellow was infused for 15 min (50 mg per kg intravenously)
      to stain the leukocyte nuclei in situ. With the use of fluorescence microscopy
      rolling leukocytes could be classified unequivocally as polymorphonuclear
      (granulocytes) or monomorphonuclear (lymphocytes/monocytes) by the shape of their
      nucleus. Irrespective of vessel depth beneath the skin surface (25-45 microm),
      most identified rolling leukocytes were classified as granulocytes (72%-100%;
      median 89%). This percentage was independent of total rolling leukocyte flux,
      systemic leukocyte count, or their in vitro differentiation pattern. In series 2,
      rats were treated with either a synthetic, highly selective E-selectin blocking
      peptide or a control peptide (intravenously, 12 mg peptide per kg bolus, followed
      by 50 mg per kg per h). E-selectin blockade significantly reduced the leukocyte
      rolling level to about 50% of baseline (p <0.01), whereas the rolling velocity
      increased (p <0.01); the control peptide had no effect. In summary, most of the
      leukocytes rolling spontaneously in postcapillary venules of intact rat skin are
      granulocytes, despite the absence of an acute inflammatory reaction. One of the
      adhesion molecules involved in this phenomenon is E-selectin.

PMID- 11841552
TI  - Expression and function of the mannose receptor CD206 on epidermal dendritic
      cells in inflammatory skin diseases.
AB  - The capability to take up mannosylated protein antigens is important for the
      biologic function of dendritic cells, as many glycoproteins derived from bacteria
      and fungi, e.g., Malassezia furfur, are mannosylated. The expression of the
      mannose receptor CD206 has been regarded a differentiation hallmark of immature
      dendritic cells, whereas monocytes and mature dendritic cells as well as
      epidermal Langerhans cells do not express CD206. This study describes some
      epidermal dendritic cells that may express CD206 under inflammatory skin
      conditions: Immunohistochemical and flow cytometric analysis with the CD206
      specific D547 antibody confirmed that Langerhans cells from normal human skin do
      not express CD206. Epidermal cell suspensions from atopic dermatitis and
      psoriasis revealed two distinct subsets of epidermal dendritic cells: a
      CD1a(+++)/CD206(-) cell population (i.e., Langerhans cells) and a
      CD1a(+)/CD206(++) cell population, corresponding to the previously described
      inflammatory dendritic epidermal cells. CD206-mediated endocytosis, assessed by
      dextran-fluorescein isothiocyanate uptake, was demonstrated in inflammatory
      dendritic epidermal cells but not in Langerhans cells. CD206-independent uptake
      of the fluorescent dye Lucifer yellow, a pinocytosis marker, was demonstrated in
      both Langerhans cells and inflammatory dendritic epidermal cells. Electron
      microscopic examination, known to distinguish Langerhans cells from inflammatory
      dendritic epidermal cells by their Birbeck granules, revealed Langerhans cells
      with Birbeck granules and inflammatory dendritic epidermal cells without Birbeck
      granules. Inflammatory dendritic epidermal cells exhibited numerous coated pits
      and vesicles, the latter fusing with large endosome-like structures, thus
      suggesting a high endocytotic activity. Immunogold staining with D547 monoclonal
      antibody confirmed that inflammatory dendritic epidermal cells were positive for
      CD206. In conclusion, inflammatory dendritic epidermal cells but not Langerhans
      cells are expressing CD206 in situ and use it for receptor-mediated endocytosis.

PMID- 11841553
TI  - Interleukin-1 receptor antagonist allele 2 and familial alopecia areata.
AB  - Alopecia areata affects 1%-2% of the population and is hypothesized to be an
      autoimmune, organ specific T-cell mediated reaction directed against the human
      hair follicle. It is characterized by loss of hair in patches (alopecia areata)
      with progression in some individuals to total loss of scalp hair (alopecia
      totalis) or to loss of all scalp and body hair (alopecia universalis). The
      interleukin-1 receptor antagonist (IL-1RN) gene was found to be associated with
      more severe clinical outcome in several chronic inflammatory diseases, including
      alopecia areata. The IL-1RN*2 allele was found to be associated with alopecia
      areata severity in a British case-control study. In this paper, we analyzed
      alopecia areata probands in a family-based sample (n = 131 parent-offspring
      trios) to study the association between alleles of the IL-1RN and various
      phenotypes of alopecia areata. In considering all patients with any form of
      alopecia areata, no association was found with IL-1RN. IL-1RN*2 allele was not
      associated with alopecia totalis and alopecia universalis. A borderline
      association was observed between IL-1RN and patchy alopecia areata but it was not
      statistically significant (p =0.06). We also observed an association between IL1
      RN*1 allele and patchy alopecia areata (p =0.045).

PMID- 11841554
TI  - Hailey-Hailey disease: molecular and clinical characterization of novel mutations
      in the ATP2C1 gene.
AB  - Hailey-Hailey disease is an autosomal dominant skin disorder characterized by
      suprabasal cell separation (acantholysis) of the epidermis. Mutations in ATP2C1,
      the gene encoding a novel, P-type Ca2+-transport ATPase, were recently found to
      cause Hailey-Hailey disease. In this study, we used conformation-sensitive gel
      electrophoresis to screen all 28 translated exons of ATP2C1 in 24 Hailey-Hailey
      disease families and three sporadic cases with the disorder. We identified 22
      different mutations, 18 of which have not previously been reported, in 25
      probands. The novel mutations comprise three nonsense, six insertion/deletion,
      three splice-site, and six missense mutations and are distributed throughout the
      ATP2C1 gene. Six mutations were found in multiple families investigated here or
      in our previous study. Haplotype analysis revealed that two of these are
      recurrent mutations that have not been inherited from a common ancestor.
      Comparison between genotype and phenotype in 23 families failed to yield any
      clear correlation between the nature of the mutation and clinical features of
      Hailey-Hailey disease. The extensive interfamilial and intrafamilial phenotypic
      variability observed suggests that modifying genes and/or environmental factors
      may greatly influence the clinical features of this disease.

PMID- 11841555
TI  - The founding members of xeroderma pigmentosum group G produce XPG protein with
      severely impaired endonuclease activity.
AB  - Of the eight human genes implicated in xeroderma pigmentosum, defects in XPG
      produce some of the most clinically diverse symptoms. These range from mild
      freckling to severe skeletal and neurologic abnormalities characteristic of
      Cockayne syndrome. Mildly affected xeroderma pigmentosum group G patients have
      diminished XPG endonuclease activity in nucleotide excision repair, whereas
      severely affected xeroderma pigmentosum group G/Cockayne syndrome patients
      produce truncated XPG proteins that are unable to function in either nucleotide
      excision repair or the transcription-coupled repair of oxidative lesions. The
      first two xeroderma pigmentosum group G patients, XP2BI and XP3BR, were reported
      before the relationship between xeroderma pigmentosum group G and Cockayne
      syndrome was appreciated. Here we provide evidence that both patients produce
      truncated proteins from one XPG allele. From the second allele, XP2BI generates
      full-length XPG of 1186 amino acids containing a single L858P substitution that
      has reduced stability and greatly impaired endonuclease activity. In XP3BR, a
      single base deletion and alternative splicing at a rare noncanonical AT-AC intron
      produces a 1185 amino acid protein containing 44 internal non-XPG residues. This
      protein is stably expressed but it also has greatly impaired endonuclease
      activity. These four XPG products can thus account for the severe ultraviolet
      sensitivity of XP2BI and XP3BR fibroblasts. These cells, unlike those from
      xeroderma pigmentosum group G/Cockayne syndrome patients, are capable of limited
      transcription-coupled repair of oxidative lesions. Our results suggest that the
      L858P protein in XP2BI and the almost full-length XPG protein in XP3BR are
      responsible for this activity and for the absence of severe early onset Cockayne
      syndrome symptoms in these patients.

PMID- 11841556
TI  - Netherton syndrome: disease expression and spectrum of SPINK5 mutations in 21
      families.
AB  - Netherton syndrome is a severe autosomal recessive skin disorder characterized by
      congenital erythroderma, a specific hair-shaft abnormality, and atopic
      manifestations with high IgE levels. Recently, we identified SPINK5, which
      encodes the serine protease inhibitor Kazal-type 5 protein (LEKTI), as the
      defective gene in Netherton syndrome. Here we describe the intron-exon
      organization of the gene and characterize the SPINK5 mutations in patients from
      21 families of different geographic origin, using denaturing high performance
      liquid chromatography and direct sequencing. We identified 18 mutations, of which
      13 were novel and seven (39%) were recurrent. The majority of the mutations were
      clustered between exons 1-8 and exons 21-26. They comprised four nonsense
      mutations (22%), eight frameshift insertions or deletions (44%), and six splice
      site defects (33%). All mutations predict the formation of premature termination
      codons. Northern blot analysis showed variable reduction of SPINK5 mutant
      transcript levels, suggesting variable efficiency of nonsense-mediated mRNA
      decay. Seven patients were homozygotes, eight were compound heterozygotes, and
      five were heterozygotes with only one identifiable SPINK5 mutation. Five
      mutations, one of which resulted in perinatal lethal disease in three families,
      were associated with certain ethnic groups. We also describe 45 intragenic
      polymorphisms in the patients studied. The clinical features of erythroderma,
      trichorrhexis invaginata, and atopic manifestations were present in the majority
      of affected individuals and ichthyosis linearis circumflexa was seen in 12 out of
      24 patients. Interfamilial and intrafamilial variation in disease severity was
      observed, with no clear correlation between mutations and phenotype, suggesting
      that the degree of severity may be affected by other factors.

PMID- 11841557
TI  - HLA-Cw6-positive and HLA-Cw6-negative patients with Psoriasis vulgaris have
      distinct clinical features.
AB  - Psoriasis is associated with HLA-Cw6, and Caucasians who carry this allele have
      about a 10-fold increased risk of developing psoriasis. We have HLA-C typed 369
      patients with familial psoriasis and compared the clinical features of the
      patients carrying HLA-Cw6 against those carrying other HLA-C types. Some striking
      clinical differences were observed between the two groups. Patients who are Cw6
      positive had a lower age at onset (p=3x10(-7)). Cw6-positive women had an earlier
      disease onset than Cw6-positive men (p =0.02), but such a difference was not
      observed for the Cw6-negative patients. The guttate-type onset of psoriasis was
      mostly confined to this group (p=2x10(-4)) and persistent disseminated guttate
      like papules were also predominantly observed in the Cw6-positive patients (p
      <10(-)4). The Cw6-positive patients also had more extensive plaques on their
      arms, legs, and trunk (p =0.001), more severe disease (p =0.003), higher
      incidence of the Koebner's phenomenon (p =0.005), reported more often that their
      psoriasis got worse during or after throat infections (p =0.02), and more often a
      favorable response to sunlight (p =0.008) In contrast, dystrophic nail changes
      were more common in the Cw6-negative patients (p =0.002) and also psoriatic
      arthritis, although this was not significant (p =0.135). It is concluded that
      patients with psoriasis have different clinical features depending on whether
      they are HLA-Cw6 positive or negative.

PMID- 11841559
TI  - Characterization of keratinocyte differentiation induced by ascorbic acid:
      protein kinase C involvement and vitamin C homeostasis.
AB  - Epidermal keratinocytes undergo differentiation in response to several stimuli to
      form the cornified envelope, a structure that contributes to the barrier function
      of skin. Although differentiation has been extensively analyzed, the precise role
      of vitamin C during this process is still not defined. Ascorbic acid, besides
      acting as a radical scavenger, has been shown to promote mesenchymal
      differentiation. In this study, we found that keratinocytes grown in ascorbate
      supplemented medium developed a differentiated phenotype, as demonstrated by
      enhanced expression of marker genes and increase in cornified envelope content.
      The pro-differentiating effects of ascorbate were mediated by the protein-kinase
      C-dependent induction of activating protein 1 DNA binding activity; indeed, down
      modulation of protein kinase C activity abolished differentiation triggered by
      ascorbic acid. Although vitamin C appeared to regulate the same signaling pathway
      modulated by calcium, a classical in vitro inducer of epidermal differentiation,
      nonetheless terminally differentiated keratinocytes exhibited different ascorbate
      homeostasis and cellular antioxidant status. Indeed, we found that, unlike
      calcium, differentiation promoted by ascorbate was accompanied by (i) an enhanced
      ascorbate transport, due to overexpression of specific transporters, (ii) a great
      efficiency of dehydroascorbate uptake, and (iii) an increase in glutathione
      content with respect to proliferating cells. Ascorbic acid may be useful to
      promote epidermal differentiation, avoiding depletion of hydrophilic antioxidant
      stores.

PMID- 11841558
TI  - Synergistic enhancement of cell-mediated immunity by interleukin-12 plus
      interleukin-2: basis for therapy of cutaneous T cell lymphoma.
AB  - Cutaneous T cell lymphoma is a clonally derived, skin-invasive malignancy of CD4+
      T lymphocytes with the phenotype of mature helper T cells. Previous work has
      demonstrated that the Sezary form, or typically leukemic form of cutaneous T cell
      lymphoma, is characterized by prominent immunologic defects, including depressed
      cell-mediated immunity associated with marked defects in the production of
      interleukin-12 and other type 1 helper T cell cytokines. Recent clinical trials
      with recombinant human interleukin-12 for cutaneous T cell lymphoma have
      demonstrated that it is a potent therapeutic agent, which induces cytotoxic T
      cell responses. Nevertheless, a high rate of refractoriness to recombinant human
      interleukin-12 occurred in these studies that may be related to the
      downmodulation of interleukin-12 receptor expression by chronic interleukin-12
      use. In an effort to enhance the overall response rate and to overcome the
      refractoriness to recombinant human interleukin-12 therapy, we studied the
      immunologic effects in vitro of adding interleukin-2 to interleukin-12 as a model
      to achieve these goals. We examined the stimulation of interferon-gamma
      production, natural killer cell activity and interleukin-12 receptor expression
      by T cells of cutaneous T cell lymphoma patients. The addition of interleukin-12
      to cutaneous T cell lymphoma patient peripheral blood cells resulted in the
      production of interferon-gamma (mean = 7914 pg per ml +/- 2161, n = 15) as did
      interleukin-2 alone (mean = 7222 pg per ml +/- 2228, n = 15). Importantly, the
      addition of interleukin-2 to the interleukin-12 synergistically enhanced the
      levels of interferon-gamma produced (mean = 16 792 pg per ml +/- 2492 n = 15) (p
      <0.01). Similarly, addition of interleukin-2 to interleukin-12 synergistically
      enhanced both the natural killer cell activity of 15 cutaneous T cell lymphoma
      patients as well as T cell surface interleukin-12 receptor expression in
      comparison with the effects of interleukin-12 or interleukin-2 alone. Thus,
      interleukin-2 plus interleukin-12 unequivocally produces the synergistic
      enhancement of multiple parameters of cell-mediated immunity as well as
      upmodulating interleukin-12 receptor expression; this indicates that protocols
      combining these two potent immune enhancing cytokines may have added therapeutic
      benefit for cutaneous T cell lymphoma.

PMID- 11841560
TI  - Agonists of proteinase-activated receptor 2 induce cytokine release and
      activation of nuclear transcription factor kappaB in human dermal microvascular
      endothelial cells.
AB  - Proteinase-activated receptor 2 belongs to a new G protein-coupled receptor
      subfamily activated by various serine proteases. It has been demonstrated to play
      a role during inflammation of many tissues including the skin. Proteinase
      activated receptor 2 is expressed by endothelial cells and regulates cutaneous
      inflammation in vivo. The underlying mechanisms of proteinase-activated receptor
      2 activation in the skin and the effects on human dermal microvascular
      endothelial cells, however, are still unknown. Agonists of proteinase-activated
      receptor 2 such as mast cell tryptase induce widespread inflammation in many
      organs including the skin. Trypsinogen is generated by endothelial cells during
      inflammation or tumor growth. Therefore we tested whether human dermal
      microvascular endothelial cells express functional proteinase-activated receptor
      2 and whether agonists of proteinase-activated receptor 2 regulate inflammatory
      responses in these cells. Calcium mobilization studies revealed that proteinase
      activated receptor 2 is functional in human dermal microvascular endothelial
      cells. Interleukin-6 and interleukin-8 were upregulated as detected by reverse
      transcription polymerase chain reaction or enzyme-linked immunosorbent assay
      indicating a role of proteinase-activated receptor 2 in stimulating human dermal
      microvascular endothelial cells. Electromobility shift assays revealed proteinase
      activated-receptor-2-induced activation of nuclear transcription factor kappaB
      with a maximum after 1 h. In conclusion, agonists of proteinase-activated
      receptor 2 upregulate interleukin-6 and interleukin-8 expression and release in
      human dermal microvascular endothelial cells. Thus, proteinase-activated receptor
      2 may play an important role in cutaneous inflammation by mediating inflammatory
      responses on dermal microvascular endothelial cells and activation of nuclear
      transcription factor kappaB.

PMID- 11841561
TI  - Failure to detect differences in proliferation status of nevi from CDKN2A
      mutation carriers and non-carriers.

PMID- 11841562
TI  - Glutathione decreases in dopaminergic PC12 cells interfere with the ubiquitin
      protein degradation pathway: relevance for Parkinson's disease?
AB  - Parkinson's disease (PD) is characterized by the presence of proteinaceous
      neuronal inclusions called Lewy bodies in susceptible dopaminergic midbrain
      neurons. Inhibition of the ubiquitin-proteasome protein degradation pathway may
      contribute to protein build-up and subsequent cell death. Ubiquitin is normally
      activated for transfer to substrate proteins by interaction with the E1 ubiquitin
      ligase enzyme via a thiol ester bond. Parkinson's disease is also characterized
      by decreases in midbrain levels of total glutathione which could impact on E1
      enzyme activity via oxidation of the active site sulfhydryl. We have demonstrated
      that increasing reductions in total glutathione in dopaminergic PC12 cells
      results in corresponding decreases in ubiquitin-protein conjugate levels
      suggesting that ubiquitination of proteins is inhibited in a glutathione
      dependent fashion. Decreased ubiquitinated protein levels appears to be due to
      inhibition of E1 activity as demonstrated by reductions in endogenous E1
      ubiquitin conjugate levels as well as decreases in the production of de novo E1
      ubiquitin conjugates when glutathione is depleted. This is a reversible process
      as E1 activity increases upon glutathione restoration. Our data suggests that
      decreases in cellular glutathione in dopaminergic cells results in decreased E1
      activity and subsequent disruption of the ubiquitin pathway. This may have
      implications for neuronal degeneration in PD.

PMID- 11841563
TI  - Intraplantar injection of glutamate evokes peripheral adenosine release in the
      rat hind paw: involvement of peripheral ionotropic glutamate receptors and
      capsaicin-sensitive sensory afferents.
AB  - Glutamate receptors have been identified on the peripheral terminals of both
      primary sensory afferents and sympathetic post-ganglionic neurons, and activation
      of these receptors produces peripheral sensitization and enhances nociception.
      Adenosine is an endogenous agent that has a regulatory effect on pain. In brain
      and spinal cord, adenosine release can be promoted by excitatory amino acids. In
      the present study, we used in vivo microdialysis to determine whether glutamate
      also can release adenosine in peripheral tissues. Rats were anesthetized with
      pentobarbital and microdialysis probes were implanted into the subcutaneous
      tissue of the plantar aspect of the rat hind paw. Subcutaneous injection of
      glutamate (50 microL, 0.3-100 micromol) evoked a short-lasting adenosine release
      immediately following drug injection. Co-administration of either the N-methyl-D
      aspartate (NMDA) receptor antagonist, dizocipine maleate (MK-801, 1 nmol) or the
      non-NMDA receptor antagonist, 6-cyano-7-nitroquinoxaline (CNQX, 10 nmol) with
      glutamate blocked such release, suggesting an involvement of peripheral
      ionotropic glutamate receptors in this response. Systemic pre-treatment with
      capsaicin, a neurotoxin selective for unmyelinated sensory afferents,
      significantly reduced glutamate-evoked peripheral adenosine release, but release
      was not affected by systemic pre-treatment with 6-hydroxydopamine, a neurotoxin
      selective for sympathetic nerve efferents. Neither MK-801 nor CNQX blocked 5%
      formalin-evoked adenosine release, suggesting adenosine release by formalin is
      not secondary to ionotropic glutamate receptor activation. We conclude that
      administration of glutamate evokes peripheral adenosine release, and that
      peripheral ionotropic glutamate receptors on unmyelinated sensory afferents are
      involved in such release. The released adenosine may provide a negative feedback
      control on nociception.

PMID- 11841564
TI  - Elevated hepatic and depressed renal cytochrome P450 activity in the Tg2576
      transgenic mouse model of Alzheimer's disease.
AB  - Recent studies indicate that the Tg2576 transgenic mouse model of Alzheimer's
      disease [tg(hAPP)] demonstrates disturbances in plasma glucose and neuroendocrine
      function reminiscent of Alzheimer's disease (AD). Alterations in any one of these
      systems can have a profound effect on hepatic cytochrome P450 (CYP) expression.
      Additionally, the recent discovery that amyloid beta 1-42 can induce the
      expression of CYP reductase in neuronal cultures further suggests that hepatic
      CYP-related metabolism may be affected by the expression of mutant human amyloid
      precursor protein in these tg(hAPP) mice. Therefore, the current study was
      conducted to investigate the activity and protein content of several CYP isoforms
      in the livers and kidneys of aged (20-month-old) tg(hAPP) mice. tg(hAPP) mice
      exhibit significant elevations in hepatic CYP2B, CYP2E1-, CYP3A- and CYP4A
      associated activities and CYP4A immunoreactive protein compared with wild-type.
      In contrast to the liver, a significant depression in renal CYP2E1- and CYP4A
      associated activities were demonstrated in tg(hAPP) mice. The presence of the
      mutant hAPP protein was detected in the brain, kidney and livers of tg(hAPP)
      mice.

PMID- 11841565
TI  - Up-regulation of tissue-type transglutaminase after traumatic brain injury.
AB  - Tissue-type transglutaminase (tTG, EC 2.3.2.13) has been implicated in various
      disease paradigms including neurodegenerative disease. In these studies, tTG
      induction after traumatic brain injury was studied using a rat cortical impact
      model. Using western blots, two forms of tTG protein expression were identified-
      an approximately 79-kDa primary form (tTG-L) and a less abundant approximately 70
      kDa form (tTG-S). Both forms of tTG protein were elevated after injury. In
      ipsilateral cortex, peak induction of tTG-L protein [561% +/- 80% of control (n =
      5)] was observed five days after injury, with expression remaining elevated after
      two weeks. Peak induction of tTG-S protein [302% +/- 81% of control (n = 5)] was
      observed three days after injury. Lesser tTG protein induction was observed in
      hippocampus. Northern blot analysis demonstrated two tTG transcripts in the
      ipsilateral cortex with peak induction of tTG-L mRNA three days after injury.
      However, tTG-S mRNA was not identified in control samples and only faintly
      detected in injured tissue. To facilitate analysis of low abundance transcripts
      in smaller tissue samples, a semiquantitative real-time PCR strategy was used.
      Semi-quantitative PCR analysis of tTG-L mRNA induction in ipsilateral cortex
      (peak after three days; 414% +/- 21% of control, n = 3) confirmed tTG-L mRNA
      induction determined by northern blot (410% of control).

PMID- 11841566
TI  - Lithium protection against glutamate excitotoxicity in rat cerebral cortical
      neurons: involvement of NMDA receptor inhibition possibly by decreasing NR2B
      tyrosine phosphorylation.
AB  - The therapeutic mechanisms of lithium for treating bipolar mood disorder remain
      poorly understood. Recent studies demonstrate that lithium has neuroprotective
      actions against a variety of insults. Here, we studied neuroprotective effects of
      lithium against excitotoxicity in cultured cerebral cortical neurons. Glutamate
      induced excitotoxicity in cortical neurons was exclusively mediated by NMDA
      receptors. Pre-treatment of cortical neurons with LiCl time-dependently
      suppressed excitotoxicity with maximal protection after 6 days of pre-treatment.
      Significant protection was observed at the therapeutic and subtherapeutic
      concentration of 0.2-1.6 mm LiCl with almost complete protection at 1 mM.
      Neuroprotection was also elicited by valproate, another major mood-stabilizer.
      The neuroprotective effects of lithium coincided with inhibition of NMDA receptor
      mediated calcium influx. Lithium pre-treatment did not alter total protein levels
      of NR1, NR2A and NR2B subunits of NMDA receptors. However, it did markedly reduce
      the level of NR2B phosphorylation at Tyr1472 and this was temporally associated
      with its neuroprotective effect. Because NR2B tyrosine phosphorylation has been
      positively correlated with NMDA receptor-mediated synaptic activity and
      excitotoxicity, the suppression of NR2B phosphorylation by lithium is likely to
      result in the inactivation of NMDA receptors and contributes to neuroprotection
      against excitotoxicity. This action could also be relevant to its clinical
      efficacy for bipolar patients.

PMID- 11841567
TI  - Prostacyclin-induced rundown of N-methyl-D-aspartate receptor currents in HEK293
      cells is protein kinase A-dependent and NR2 subunit-selective.
AB  - Previous studies in neurons have demonstrated a rapid decrease in NMDA receptor
      currents following tyrosine kinase inhibition or exposure to platelet-derived
      growth factor (PDGF). Inhibitors of protein kinase A (PKA) block the PDGF-induced
      rundown suggesting a multistep pathway that leads to decreased amplitudes of NMDA
      activated currents. In this study, HEK293 cells expressing different NMDA
      receptor subunits were used to study the effects of prostacyclin receptor
      mediated PKA activation on the magnitude of glutamate-activated currents. The
      prostacyclin agonist iloprost induced a rapid and time-dependent depression of
      otherwise stable glutamate-activated currents in cells expressing NR1-2a/2A or
      NR1-2a/2D receptors but not NR1-2a/2B or NR1-2a/2C receptors. This rundown was
      prevented by treatment of cells with the PKA inhibitor H89. The iloprost effect
      persisted in cells coexpressing NR1-2a/2A receptors and either wild-type or
      mutant Src kinase (SrcS17A). Co-expression of PSD-95 with NR1-2a/2A receptors
      reduced but did not eliminate the extent of rundown. Iloprost also produced
      current rundown in cells expressing NR1-2a and a C-terminal truncated NR2A
      subunit (NR2A1050stop) but not in those transfected with an NR2A tyrosine mutant
      (Y842F). The iloprost-induced rundown of wild-type NR1-2a/2A receptors was
      prevented by prior exposure of cells to hypertonic sucrose. These results suggest
      that PKA influences the functional activity of NMDA receptors in an NR2 subunit
      selective fashion.

PMID- 11841568
TI  - Sequential induction of embryonic and adult forms of glutamic acid decarboxylase
      during in vitro-induced neurogenesis in cloned neuroectodermal cell-line, NE-7C2.
AB  - The expression of different forms of glutamate decarboxylases and GABA was
      investigated in the course of retinoic acid-induced neuronal differentiation of
      NE-7C2 cell-line established from brain vesicles of 9-day-old mouse embryos
      lacking functional p53 gene. Non-induced NE-7C2 cells expressed embryonic GAD
      mRNAs with a low level of embryonic GAD25 protein and did not contain detectable
      amounts of GABA. Addition of 10(-6) M retinoic acid induced the expression of N
      tubulin and a significant increase in the level of embryonic GAD messages and
      GAD25 protein in early stage differentiating neurones. The enzymatically active
      embryonic GAD44 was detected at later stages of induction in neurone-like cells
      and showed a maximum of expression at the time of neurite elongation and network
      formation. With the advance of neuronal maturation, the expression of embryonic
      forms declined while the adult GAD65 and GAD67 transcripts became dominant. GABA
      containing neurones were first demonstrated on the sixth day of induction
      coinciding with the peak of GAD44 expression and the beginning of GAD65
      expression. The sequential induction of different GAD forms and the stage
      dependent GABA synthesis in NE-7C2 cells is highly reminiscent of the temporal
      pattern found in vivo and suggests that these processes might be involved in the
      differentiation of neuronal progenitors.

PMID- 11841570
TI  - Formation of carnosine-Cu(II) complexes prevents and reverts the inhibitory
      action of copper in P2X4 and P2X7 receptors.
AB  - To further analyze the action of copper on brain synaptic mechanisms, the brain
      dipeptide carnosine (beta-alanyl-L-histidine) was tested in Xenopus laevis
      oocytes expressing the rat P2X4 or P2X7 receptors. Ten micromolar copper halved
      the currents evoked by ATP in both receptors; co-application of carnosine plus
      copper prevented the metal induced-inhibition with a median effective
      concentration of 12.1 +/- 3.9 and 12.0 +/- 5.5 microm for P2X4 and P2X7,
      respectively. Zinc potentiated only the P2X4 ATP-evoked currents; carnosine had
      no effect over this metal. The relative potency and selectivity of classical
      metal chelators to prevent the copper inhibition was compared between carnosine
      and penicillamine (PA), bathophenanthroline (BPh) or L-histidine (His). Their
      rank order of potency in P2X4 and P2X7 receptors was carnosine = PA = His > BPh >
      Glycine (Gly) and carnosine = BPh = His > PA > Gly, respectively. The potency to
      prevent the zinc-induced potentiation in the P2X4 receptor was BPh > PA > His;
      carnosine, Gly and beta-alanine were inactive. Whereas 1-100 microm carnosine or
      His alone did not modify the ATP-evoked currents, 10-100 microm PA augmented and
      100 microm BPh decreased the ATP-evoked currents. Carnosine was able to revert
      the copper-induced inhibition restoring the maximal ATP gated current in a
      concentration-dependent manner. Electronic spectroscopy confirm the formation of
      carnosine-Cu(II) complexes, mechanism that can account for the prevention and
      reversal of the copper inhibition, revealing its potential in copper intoxication
      treatment.

PMID- 11841569
TI  - Mitochondrial DNA and respiratory chain function in spinal cords of ALS patients.
AB  - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized
      by selective motor neuron death. In order to address the question of a putative
      role of mitochondrial dysfunction in the pathogenesis of ALS, we studied the
      mitochondrial DNA (mtDNA) and mitochondrial respiratory chain enzyme activities
      in spinal cords of ALS patients and in control subjects without neuropathologic
      abnormalities. Using a "double PCR and digestion" technique to estimate the
      levels of randomly distributed point mutations in two small regions of the mtDNA,
      we found significantly higher levels of mutant mtDNA in the spinal cord of ALS
      patients compared to controls. No large-scale rearrangements were found, but the
      amount of mtDNA, measured by Southern blot, was significantly lower in the ALS
      samples. This reduction correlated well with a decrease of citrate synthase (CS)
      activity, a mitochondrial marker, as were the activities of respiratory chain
      complexes I + III, II + III, and IV, suggesting a loss of mitochondria in ALS
      spinal cords.

PMID- 11841571
TI  - Role of Ca2+ and calmodulin-dependent enzymes in the regulation of glycine
      transport in Muller glia.
AB  - Glycine (Gly) is considered an obligatory co-agonist at NMDA receptors. Muller
      glia from the retina harbor functional NMDA receptors, as well as low and high
      affinity Gly transporters, the later identified as GLYT1. We here studied the
      regulation of Gly transport in primary cultures of Muller glia, as this process
      could contribute to the modulation of NMDA receptor activity at glutamatergic
      synapses in the retina. We demonstrate that neither glutamate stimulation nor the
      activation or inhibition of protein kinases A or C modify transport. In order to
      assess a function for Ca2+ and calmodulin (CaM)-dependent processes in the
      regulation of Gly transport, we explored the participation of Ca2+ concentration,
      CaM and Ca2+/CaM-dependent enzymes on Gly transporter activity. ATP and
      carbachol, known to induce Ca2+ waves in Muller cells, as well as caffeine
      induced Ca2+ release from intracellular stores stimulated transport, whereas Ca2+
      chelation by BAPTA-AM markedly reduced transport. CaM inhibitors W-7, ophiobolin
      A, R-24571 and trifluoperazine, induced a specific dose-dependent inhibition of
      transport. The inhibition of CaMKII by the autocamtide-2-related inhibitory
      peptide or by KN62 caused a decrease in transport which, in the case of KN62, was
      due to the abolition of the high affinity component, ascribed to GLYT1. Our
      results further suggest that Gly transport is under cytoskeletal control, as
      activation of calpain by major increases in [Ca2+]i induced by ionophores, as
      well as actin destabilization clearly inhibit uptake. We here demonstrate for the
      first time the participation of CaM, CaMKII and the actin cytoskeleton in the
      regulation of Gly transport in glia. Ca2+ waves are induced in Muller cells by
      distinct neuroactive compounds released by neurons and glia, hence the regulation
      of [Gly] by this system may be of physiological relevance in the control of
      retinal excitability.

PMID- 11841572
TI  - Involvement of GABA and cholinergic receptors in the nucleus accumbens on
      feedback control of somatodendritic dopamine release in the ventral tegmental
      area.
AB  - The objectives of the present study were to examine the involvement of GABA and
      cholinergic receptors within the nucleus accumbens (ACB) on feedback regulation
      of somatodendritic dopamine (DA) release in the ventral tegmental area (VTA).
      Adult male Wistar rats were implanted with ipsilateral dual guide cannulae for in
      vivo microdialysis studies. Activation of the feedback system was accomplished by
      perfusion of the ACB with the DA uptake inhibitor GBR 12909 (GBR; 100 microm). To
      assess the involvement of GABA and cholinergic receptors in regulating this
      feedback system, antagonists (100 microm) for GABAA (bicuculline, BIC), GABAB
      (phaclofen, PHAC), muscarinic (scopolamine, SCOP), and nicotinic (mecamylamine,
      MEC) receptors were perfused through the probe in the ACB while measuring
      extracellular DA levels in the ACB and VTA. Local perfusion of the ACB with GBR
      significantly increased (500% of baseline) the extracellular levels of DA in the
      ACB and produced a concomitant decrease (50% of baseline) in the extracellular DA
      levels in the VTA. Perfusion of the ACB with BIC or PHAC alone produced a 200
      400% increase in the extracellular levels of DA in the ACB but neither antagonist
      altered the levels of DA in the VTA. Co-perfusion of either GABA receptor
      antagonist with GBR further increased the extracellular levels of DA in the ACB
      to 700-800% of baseline. However, coperfusion with BIC completely prevented the
      reduction in the extracellular levels of DA in the VTA produced by GBR alone,
      whereas PHAC partially prevented the reduction. Local perfusion of the ACB with
      either MEC or SCOP alone had little effect on the extracellular levels of DA in
      the ACB or VTA. Co-perfusion of either cholinergic receptor antagonist with GBR
      markedly reduced the extracellular levels of DA in the ACB and prevented the
      effects of GBR on reducing DA levels in the VTA. Overall, the results of this
      study suggest that terminal DA release in the ACB is under tonic GABA inhibition
      mediated by GABAA (and possibly GABAB) receptors, and tonic cholinergic
      excitation mediated by both muscarinic and nicotinic receptors. Activation of
      GABAA (and possibly GABAB) receptors within the ACB may be involved in the
      feedback inhibition of VTA DA neurons. Cholinergic interneurons may influence the
      negative feedback system by regulating terminal DA release within the ACB.

PMID- 11841574
TI  - Hydrocortisone decreases retinal endothelial cell water and solute flux
      coincident with increased content and decreased phosphorylation of occludin.
AB  - Corticosteroids provide an effective treatment to reduce edema for conditions in
      which the blood-brain or blood-retinal barrier is compromised. However, little is
      known about the mechanism by which these hormones affect endothelial cell
      function. We hypothesized that hydrocortisone would reduce transport of water and
      solutes across bovine retinal endothelial cell (BREC) monolayers coincident with
      changes to the tight junction protein occludin. Treatment of BREC with 103 nm
      hydrocortisone for two days significantly decreased water and solute transport
      across cell monolayers. Immunoblot analysis of occludin extracted in SDS or urea
      based buffers revealed a 1.65- or 2.57-fold increase in content, respectively. A
      similar two-fold increase in occludin mRNA was observed by real-time PCR.
      Immunocytochemistry revealed hydrocortisone dramatically increased both occludin
      and ZO-1 staining at the cell border. Additionally, 4 h of hydrocortisone
      treatment significantly reduced occludin phosphorylation. To our knowledge, this
      is the first example of a regulated decrease in occludin phosphorylation
      associated with increased barrier properties. In conclusion, hydrocortisone
      directly affects retinal endothelial cell barrier properties coincident with
      changes in occludin content, phosphorylation and tight junction assembly.
      Localized hydrocortisone therapy may be developed as a treatment option for
      patients suffering from retinal edema due to diabetes.

PMID- 11841573
TI  - Participation of protease-activated receptor-1 in thrombin-induced microglial
      activation.
AB  - Activation of microglia, the resident macrophages in the CNS, plays a significant
      role in neuronal death or degeneration in a broad spectrum of CNS disorders.
      Recent studies indicate that nanomolar concentrations of the serine protease,
      thrombin, can activate microglia in culture. However, in contrast to other neural
      cells responsive to thrombin, the participation of novel protease-activated
      receptors (PARs), such as the prototypic thrombin receptor PAR1, in thrombin
      induced microglial activation was cast in doubt. In this report, by utilizing
      primary microglial cultures from PAR1 knockout (PAR1-/-) mice, application of the
      PAR1 active peptide TRAP-6 (SFLLRN) in comparison to a scrambled peptide (LFLNR),
      we have unambiguously demonstrated that murine microglia constitutively express
      PAR1 mRNA that is translated into fully functional protein. Activation of the
      microglial PAR1 induces a rapid cytosolic free [Ca2+]i increase and transient
      activation of both p38 and p44/42 mitogen-activated protein kinases. Moreover,
      although in part, this PAR1 activation directly contributes to thrombin-induced
      microglial proliferation. Furthermore, although not directly inducing tumor
      necrosis factor-alpha (TNF-alpha) release, PAR1 activation up-regulates
      microglial CD40 expression and potentiates CD40 ligand-induced TNF-alpha
      production, thus indirectly contributing to microglial activation. Taken
      together, these results demonstrate an essential role of PAR1 in thrombin-induced
      microglial activation. In addition, strategies aimed at blocking thrombin
      signaling through PAR1 may be therapeutically valuable for diseases associated
      with cerebral vascular damage and significant inflammation with microglial
      activation.

PMID- 11841575
TI  - The human histamine H2-receptor couples more efficiently to Sf9 insect cell Gs
      proteins than to insect cell Gq-proteins: limitations of Sf9 cells for the
      analysis of receptor/Gq-protein coupling.
AB  - The human histamine H2-receptor (hH2R) couples to Gs-proteins to activate
      adenylyl cyclase and to Gq-proteins to activate phospholipase C, but
      phospholipase C activation has not consistently been observed. The aim of this
      study was to compare coupling of hH2R to insect and mammalian Gs- and Gq-proteins
      in Spodoptera frugiperda (Sf9) cells. Interaction of hH2R with mammalian G
      proteins was assessed with coexpressed proteins or receptor-Galpha fusion
      proteins that enhance coupling efficiency. hH2R efficiently coupled to insect Gs
      proteins to activate adenylyl cyclase. However, hH2R poorly coupled to insect Gq
      proteins as assessed by the lack of enhancement of histamine-stimulated steady
      state GTP hydrolysis by regulators of G protein signaling (RGS proteins). In
      contrast, RGS-proteins efficiently enhanced GTP hydrolysis stimulated by the
      human platelet-activating factor receptor (PAFR) and the histamine H1-receptor
      (H1R) from man and guinea pig. The measurement of intracellular free Ca2+
      concentration was not useful for studying receptor/Gq-protein coupling. hH2R also
      efficiently interacted with mammalian Gs-proteins, specifically with fused
      Gsalpha as assessed by guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS)-sensitive
      high-affinity agonist binding, agonist-stimulated [35S]GTPgammaS binding and
      adenylyl cyclase activation. In contrast, coupling of hH2R to coexpressed and
      fused mammalian Gqalpha was poor. However, our inability to reconstitute
      efficient coupling of PAFR and H1R to mammalian Gqalpha indicated that a large
      portion of the expressed G protein was functionally inactive. Taken together, our
      data show that hH2R couples more efficiently to insect cell Gs-proteins than to
      insect cell Gq-proteins. Unfortunately, there are significant limitations in the
      usefulness of Sf9 cells for comparing the coupling of receptors to mammalian Gs-
      and Gq-proteins and assessing Gq-mediated activation of effector systems.

PMID- 11841576
TI  - Ceramide activates microglia to enhance the production/secretion of brain-derived
      neurotrophic factor (BDNF) without induction of deleterious factors in vitro.
AB  - In analyzing the regulation of neurotrophin production/secretion from microglia,
      C8-ceramide (D-erythro-sphingosine, N-octanoyl-) was found to induce secretion of
      brain-derived neurotrophic factor (BDNF) from microglia in vitro. In the present
      study, the action of C8-ceramide in secreting neurotrophic and harmful factors
      was investigated and compared with the effects of lipopolysaccharide (LPS). C8
      ceramide as well as LPS enhanced the production/secretion of BDNF but, different
      from LPS, did not induce tumor necrosis factor alpha, interleukin-1beta, or
      nitric oxide. The C8-ceramide-induced BDNF release was significantly suppressed
      by protein kinase C (PKC) inhibitor, bisindolylmaleimide, which targets PKC
      isoforms, alpha, beta, gamma, delta and epsilon. However, it was not suppressed
      by a specific inhibitor of PKCalpha. Furthermore, PKCbeta and gamma were
      undetected in the microglia. Therefore, PKCdelta and/or epsilon appear to be
      functioning PKC isoforms. In contrast, none of the mitogen-activated protein
      kinases (MAPKs) and none of the transcription factors, including the cAMP
      response element-binding transcription factor (CREB) and nuclear factor kappaB
      (NFkappaB) were activated in the microglia in response to C8-ceramide. These
      results indicate that ceramide-induced BDNF release in microglia is mediated by a
      signaling pathway associated with PKCdelta and/or epsilon, but not with
      activation of MAPKs, CREB and NFkappaB.

PMID- 11841577
TI  - Multiple mechanisms of transmitter release evoked by "pathologically" elevated
      extracellular [K+]: involvement of transporter reversal and mitochondrial
      calcium.
AB  - The release of [3H]GABA evoked by depolarization with various concentrations of
      KCl was studied using superfused rat cerebrocortex synaptosomes. Elevating [K+]
      produced release of [3H]GABA over basal which was increasingly less dependent on
      external Ca2+ but more sensitive to the GABA transporter blocker SKF 100330 A.
      Accordingly, the sensitivity to clostridial toxins of the depolarization-evoked
      amino acid release was inversely correlated to the concentration of KCl used.
      However, at 50 mM K+, one-third of the stimulated release remained which was
      external Ca2+-independent but insensitive to SKF 100330 A. This release was
      prevented by BAPTA, thapsigargin or dantrolene; it also was inhibited by blocking
      in mitochondria the ATP production with oligomycin, the H+-dependent Ca2+
      uniporter with RU 360, the Na+/Ca2+ exchanger with CGP 37157 or by lowering
      extraterminal [Na+]. In fluorescence experiments with fura-2/AM, 50 mM K+ (in
      Ca2+ free medium) caused elevation of cytosolic [Ca2+] that was sensitive to
      thapsigargin or CGP 37157; these compounds produced partially additive effects.
      When exocytosis was monitored with the fluorescent dye acridine orange, the
      fluorescence elicited by 50 mM K+ was sensitive to thapsigargin or CGP 37157,
      which produced additive effects, and to low-Na+ media. To conclude, extracellular
      K+ concentrations occurring in the CNS in certain pathological conditions provoke
      GABA release by mechanisms different from classical exocytosis. These include
      carrier-mediated release and internal Ca2+-dependent exocytosis; in the latter,
      mitochondrial Ca2+ seems to play a primary role.

PMID- 11841578
TI  - Geldanamycin specifically modulates thrombin-mediated morphological changes in
      mouse neuroblasts.
AB  - Regulation of neuronal morphology and extension of cell processes are required
      for normal synaptic connections and signaling. Thrombin, a serine protease,
      regulates neuronal morphological changes by activating protease activated
      receptor-1 (PAR-1), a seven-transmembrane G protein-coupled receptor. Thrombin
      mediated morphological changes precede its diverse action on neurons, and the
      drugs that regulate these morphological changes have important therapeutic
      implications. The present study was carried out to evaluate the role of
      geldanamycin, a specific inhibitor of Hsp90 on thrombin-induced regulation of
      neuronal morphology. Incubation of mouse neuroblasts (NB2a) with geldanamycin
      prevented thrombin-mediated neurite retraction in a dose-dependent manner.
      Geldanamycin also blocked thrombin-induced activation of RhoA, a small GTP
      binding protein involved in the cytoskeletal signaling. To determine the
      specificity of geldanamycin action, its effect on lysophosphatidic acid (LPA)
      induced morphological changes was examined. Geldanamycin did not have any effect
      on LPA-induced neurite retraction and RhoA activation indicating a specific role
      for this drug in the regulation of thrombin-mediated morphological changes.

PMID- 11841593
TI  - No evidence for a phase delay in human circadian rhythms after a single morning
      melatonin administration.
AB  - Although there is good consensus that a single administration of melatonin in the
      early evening can phase advance human circadian rhythms, the evidence for phase
      delay shifts to a single melatonin stimulus given in the early morning is sparse.
      We therefore carried out a double-blind randomized-order placebo-controlled study
      under modified constant routine (CR) conditions (58 hr bedrest under
      approximately 8 lux with sleep 23:00-07:00 hr) in nine healthy young men. A
      single (pharmacological) dose of melatonin (5 mg p.o.) or a placebo was
      administered at 07:00 hr on the first morning. Core body temperature (CBT) and
      heart rate (HR) were continuously recorded, and saliva was collected half-hourly
      for assay of melatonin. Neither the timing of the mid-range crossing times of
      temperature (MRCT) and HR rhythms, nor dim light melatonin onset (DLMOn) or
      offset (DLMOff) were phase shifted the day after melatonin administration
      compared with placebo. The only change was an altered wave form of the CBT
      rhythm: longer duration of higher-than-average temperature after melatonin
      administration. Under the same modified CR conditions we have previously
      demonstrated a clear phase advance of the above circadian rhythms following a
      single administration of 5 mg melatonin in the evening. This study's failure to
      find significant delays to a single administration does not negate other positive
      findings with multiple doses, which may be necessary for a 'weak zeitgeber'.

PMID- 11841594
TI  - Melatonin induces tyrosine hydroxylase mRNA expression in the ventral
      mesencephalon but not in the hypothalamus.
AB  - We have evaluated the effect of chronic administration of melatonin in terms of
      mRNA expression for tyrosine hydroxylase (TH), the rate-limiting enzyme in
      catecholamine biosynthesis, and in the terms of dopamine (DA) transporter (DAT)
      by means of in situ hybridization. Experimental rats received daily late
      afternoon injections of 1.5 mg/kg melatonin for 30 days and analysis were
      performed in the ventral mesencephalon including the substantia nigra (SN) and
      ventral tegmental area (VTA), and hypothalamus. In the ventral mesencephalon,
      melatonin treatment significantly induced TH mRNA levels in individual
      dopaminergic neurons in SN and VTA. In contrast, DAT mRNA levels remained at
      control levels. Striatal synaptosomal DA uptake was not modified by melatonin
      treatment as compared with controls. Analysis of glutamic acid decarboxylase
      (GAD) mRNA in SN, the biosynthetic enzyme for GABAergic neurons, revealed no
      effect of melatonin treatment on mRNA levels for this marker. In the
      hypothalamus, we performed mRNA quantitation for TH in arcuate nucleus (Arc) and
      supraoptic nucleus (SO). Melatonin treatment failed to alter mRNA levels in
      either area. We detected weak but significant mRNA levels for DAT in Arc, SO,
      zona incerta (ZI) and periventricular hypothalamic nucleus (Pe). However, because
      of the low levels of mRNA in hypothalamic areas we were unable to perform a
      reliable measurement of DAT mRNA levels in response to melatonin treatment. We
      conclude that melatonin administration, that combines antioxidant capacity and a
      tissue-specific TH inducing effect, may be useful as a pharmacological agent to
      protect dopaminergic neurons from degeneration.

PMID- 11841595
TI  - Testicular activity is restored by melatonin replacement after suprachiasmatic
      nucleus lesion or superior cervical ganglionectomy in mink.
AB  - Subcutaneous melatonin implants were inserted in mink subjected to natural
      (autumn) or experimental gonadostimulatory short-days (4L:20D), after lesion of
      the suprachiasmatic nucleus (SCNx) or after superior cervical ganglionectomy
      (SCGx). Gonad stimulation was assessed by measuring testicular volume and plasma
      testosterone level. In SCNx and SCGx animals, all measurements were indicative of
      sexual quiescence. In contrast, both SCNx and SCGx animals with melatonin,
      maintained in natural or experimental gonadostimulating short-days, showed an
      increase in testicular activity 2 months after melatonin implantation. Thus,
      melatonin (and pineal activity) is a prerequisite for the photoperiodic
      stimulation of reproductive activity, and the SCN is not necessarily the target
      site for melatonin action on the renewal of reproduction in the mink.

PMID- 11841596
TI  - The effect of melatonin on bleomycin-induced pulmonary fibrosis in rats.
AB  - The present investigation was designed to determine the protective effects of
      melatonin against bleomycin (BLM)-induced oxidant lung toxicity. Wistar-albino
      rats were divided into four groups: saline (SA, 0.4 mL/animal), 1% ethanol-saline
      (ALC, 0.4 mL/animal), bleomycin sulphate (BLM, 10 mg/kg), or bleomycin sulphate +
      melatonin (BLM, 10 mg/kg + MLT, 10 mg/kg). All injections were given
      intraperitoneally (i.p.), twice weekly for a period of 3 wk (a total of seven
      injections for each group). Twenty-five days after BLM treatment, pulmonary
      fibrosis was assessed as hydroxyproline content in lung homogenates. Findings
      show that BLM-induced pulmonary injury resulted in increases in bronchoalveolar
      lavage fluid (BALF) biomarkers including total protein, lactate dehydrogenase
      (LDH), glutathione-peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase
      (CAT). Additionally, the levels of thiobarbituric acid reactive substances
      (TBARS), an index of lipid peroxidation (LPO), were also increased in BALF.
      Conversely, the level of glutathione (GSH) was reduced in BALF of BLM-treated
      rats. Melatonin provided protection against BLM-induced pulmonary fibrosis by
      suppressing oxidative stress. It abolished BLM-stimulated LPO and reversed the
      imbalance between oxidants and antioxidants in the BALFs. Results thus indicate
      that melatonin inhibits BLM-induced lung toxicity associated with oxidative
      damage.

PMID- 11841597
TI  - Long-term melatonin administration reduces hyperinsulinemia and improves the
      altered fatty-acid compositions in type 2 diabetic rats via the restoration of
      Delta-5 desaturase activity.
AB  - The objective of this study was to investigate the effect of long-term melatonin
      administration on plasma levels of triglycerides, insulin and leptin, and on the
      fatty-acid metabolism of plasma and hepatic lipids in type 2 diabetic rats.
      Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an animal model of type 2
      diabetes mellitus, were divided into two groups: one untreated (n=6), and one
      implanted with time-releasing melatonin pellets (1.1 mg/day for 30 wk) under the
      abdominal skin (n=6). Age-matched Long-Evans Tokushima Otsuka (LETO) rats (n=6)
      were used as healthy controls. The untreated diabetic rats had the increased
      plasma levels of triglycerides, cholesterol, insulin and leptin at 35 wk, as
      compared with the healthy control rats (n=6). The diabetic rats also had
      augmented ratios of 20:3n-6/20:4n-6 fatty acids, owing to diminished activity of
      Delta-5 desaturase, an insulin-permissive enzyme, in the liver. Melatonin
      administration to OLETF rats reduced the hypertriglyceridemia (-39%, P < 0.05),
      hyperinsulinemia (-33%, P < 0.01) and hyperleptinemia (-43%, P < 0.01), and
      restored hepatic Delta-5 desaturase activity (148%, P < 0.005). This resulted in
      a return to normal ratios of 20:3n-6/20:4n-6 fatty acids in plasma and hepatic
      lipids. There was a significant correlation (r=0.64, P < 0.005) between plasma
      levels of insulin and the ratios of 20:3n-6/20:4n-6 in plasma phospholipids of
      all rats in the three groups. Thus, subcutaneous implantation of a melatonin
      releasing pellet thus resulted in improved lipid metabolism in diabetic rats,
      probably through restored insulin resistance.

PMID- 11841598
TI  - Influence of light intensity, spectrum and orientation on sea bass plasma and
      ocular melatonin.
AB  - Melatonin is involved in the transduction of light information and the
      photoperiodic control of many important physiological functions in fish. Although
      artificial photoperiods have been used to improve fish growth and manipulate
      reproduction, there is little information about the characteristics of light
      'quality'. In this paper we describe the effects of a light pulse in the middle
      of the dark phase on plasma and ocular melatonin in European sea bass. We first
      determined the light intensity necessary to elicit a melatonin response using
      white light of varying intensities (0.6-600 mu W/cm(2), experiment 1). Secondly,
      we tested the effect of the light spectrum on melatonin production using three
      differently coloured lights (half-peak bandwidth=434-477, 498-575 and 610-687 nm
      for the blue, green and red lamp, respectively, experiment 2) and, finally, we
      determined the effect of light orientation (downwards directed versus upwards
      directed, experiment 3). The results show that the minimum light intensity needed
      to inhibit or stimulate melatonin levels in both plasma and the eye was 6.0 mu
      W/cm(2). A linear correlation was found between the logarithm of light intensity
      and the relative inhibition. In addition, the blue wavelength was more effective
      in decreasing melatonin levels in the former and increasing the levels in the
      latter. Nevertheless, red light at sufficient intensity proved effective at
      significantly suppressing circulating melatonin. Downwards light had a greater
      effect than upward-directed illumination in suppressing plasma melatonin. In
      conclusion, the results point to the importance of giving proper consideration to
      the characteristics of light, to adequately control melatonin production and its
      related physiological processes.

PMID- 11841599
TI  - A multifactorial approach employing melatonin to accelerate resynchronization of
      sleep-wake cycle after a 12 time-zone westerly transmeridian flight in elite
      soccer athletes.
AB  - Rapid transmeridian translocation through multiple time zones has a negative
      impact on athletic performance. The aim of the present study was to test the
      timely use of three factors (melatonin treatment, exposure to light, physical
      exercise) to hasten the resynchronization of a group of elite sports competitors
      and their coaches to a westerly transmeridian flight comprising of 12 time-zones.
      Twenty-two male subjects were included in the study. They were professional
      soccer players and their coaches who travelled to Tokyo to play the final game of
      the Intercontinental Coup. The day prior to departure, urine was collected from
      each subject from 18:00 to 06:00 hrs to measure the melatonin metabolite 6
      sulphatoxymelatonin. Participants were asked to complete sleep log diaries from
      day 0 (preflight) to the day before returning to Buenos Aires (day 8). All
      subjects received 3 mg of melatonin p.o. daily at expected bedtime at Tokyo
      immediately after leaving Buenos Aires. Upon arrival at Tokyo the subjects
      performed a daily physical exercise routine outdoors at two restricted times of
      the day (from 08:00 to 11:00 hrs in the morning and from 13:00 to 16:00 hrs in
      the afternoon). Exposure to sunlight or physical exercise at other times of the
      day was avoided. Except for the number of awakenings (which increased on days 1
      and 3) and sleep latency (which decreased on days 2, 6 and 8), there was an
      absence of significant changes in subjective sleep parameters as compared with
      preflight assessment. Sleep quality and morning alertness at Tokyo correlated
      significantly with preflight 6-sulphatoxymelatonin excretion. Mean
      resynchronization rate of sleep-wake cycle to the 12 hr-time shift was 2.13 +/-
      0.88 days, significantly different from the minimal resynchronization rate of 6
      days expected after a 12-time-zones flight. The results indicate that the
      combination of melatonin treatment, an appropriate environmental light schedule
      and timely applied physical exercise can be useful to help elite athletes to
      overcome the consequences of jet lag.

PMID- 11841600
TI  - Melatonin attenuates MPTP-induced dopaminergic neuronal injury associated with
      scavenging hydroxyl radical.
AB  - To clarify the relationship between melatonin's hydroxyl radical (*OH) scavenging
      ability and its protective effect in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
      (MPTP)-induced neuronal injury, in the present study, the salicylate trapping
      method combined with high-performance liquid chromatography (HPLC)
      electrochemical detection were used to measure the contents of dihydroxybenzoic
      acid (DHBA) and dopamine (DA) in brain tissues of C57BL/6 mice.
      Immunocytohistochemistry was used to detect tyrosine hydroxylase (TH)-like
      positive staining neurons. Results show that MPTP treatment induced an increase
      in the content of DHBA and decrease in the level of DA as well as the number of
      TH positive stained neurons in the mouse brain. However, melatonin dose
      dependently inhibited the increase of DHBA levels in ventral midbrain tissues,
      the decrease of DA content and the loss of dopaminergic neurons. Moreover, the
      relationship between the changes of DHBA and DA levels in the brain of mice
      following MPTP and melatonin treatment showed a statistically significant
      negative correlation. Present results suggest that melatonin can ameliorate MPTP
      induced dopaminergic neuronal lesions probably, at least partially, because of
      its inhibition of *OH generation.

PMID- 11841601
TI  - Melatonin reduces phosphine-induced lipid and DNA oxidation in vitro and in vivo
      in rat brain.
AB  - Phosphine (PH(3)), a widely used pesticide, was found in our recent study to
      induce oxidative damage in the brain, liver and lung of rats. We also observed
      that melatonin significantly blocked this action. The present study focused on
      brain and the magnitude and mechanism of protection of PH(3)-induced oxidative
      damage by melatonin in vitro and in vivo. PH(3) in whole brain homogenate (3 mg
      protein/mL Tris-HCl pH 7.4 buffer) induced increasing lipid peroxidation [as
      malondialdehyde (MDA) and 4-hydroxyalkenals (4-HDA)] dependent on concentration
      (0.25-2 mM) and time (30-150 min), reaching a maximum level of 2.9-fold at 90 min
      after PH(3) at 1 mM. Elevation of MDA + 4-HDA levels by PH(3) at 1 mM was also
      observed in homogenates of cerebral cortex, cerebellum, hippocampus and
      hypothalamus examined individually. Melatonin at 0.1-2 mM progressively inhibited
      PH(3)-induced lipid peroxidation in brain and regions thereof. Additionally,
      PH(3) induced brain DNA oxidation in vitro and in vivo determined as 8
      hydroxyguanosine (8-OH-dG). Melatonin at 1 mM significantly suppressed PH(3)
      induced brain DNA oxidation in vitro. PH(3) at 4 mg/kg i.p. significantly
      elevated 8-OH-dG in frontal cortex and melatonin prevented it. PH(3) in vivo
      marginally lowered brain glutathione peroxidase activity and melatonin restored
      it completely. In contrast, PH(3) and melatonin both stimulated superoxide
      dismutase production. Brain glutathione (GSH) levels in PH(3)-treated rats were
      significantly reduced at 30 min and recovered gradually. It is concluded that
      melatonin, probably because of its free radical scavenging ability, confers
      marked protection against PH(3)-induced oxidative toxicity in brain.

PMID- 11841602
TI  - Increased melatonin 1a-receptor immunoreactivity in the hippocampus of
      Alzheimer's disease patients.
AB  - The pineal secretory product melatonin has, in addition to regulating retinal,
      circadian and vascular functions, neuroprotective effects. Blood melatonin levels
      are often decreased in Alzheimer's disease (AD), a progressively disabling
      neurodegenerative disorder. In this study we provide the first
      immunohistochemical evidence for the localization of melatonin 1a-receptor
      (MT(1)) in aged human hippocampus and a comparison of AD cases. MT(1) was
      localized to pyramidal neurons in the hippocampal cornu ammonis (CA)1-4
      subfields. There was a distinct increase in staining intensity in all AD cases
      indicating an up-regulation of the receptor, possibly as a compensatory response
      to impaired melatonin levels in order to augment melatonin's neuroprotective
      effects.

PMID- 11841604
TI  - Gene therapy and renal disease. Introduction.

PMID- 11841603
TI  - Homocysteine levels are increased due to lack of melatonin in pinealectomized
      rats: is there a link between melatonin and homocysteine?

PMID- 11841605
TI  - Herpes simplex virus as a model vector system for gene therapy in renal disease.
AB  - The past decade has been marked by significant advances in the application of
      gene transfer into living cells of animals and humans. These approaches have been
      tested in a few animal models of inherited and acquired renal diseases, including
      carbonic anhydrase II deficiency [1] and experimental glomerulonephritis [2, 3].
      Gene transfer into proximal tubular cells has been successfully accomplished by
      intrarenal arterial infusion of a liposomal complex [4] or an adenoviral vector
      [5]. Tubular cells from the papilla and medulla have been selectively transduced
      by retrograde infusion into the pelvi-calyceal system of an adenoviral vector
      containing a reporter for beta-galactosidase [5]. Although the results of these
      initial studies are promising, further studies to optimize viral vectors,
      maximize gene delivery, minimize side-effects, and develop cell-specific and long
      term regulated gene expression are critical to the success of gene therapy
      targeted to specific compartments of the kidney. Our recent efforts have focused
      on defining the cellular pathways responsible for viral entry and infection into
      renal epithelial cells using herpes simplex virus (HSV) as a model vector. We
      anticipate that a solid understanding of the basic scientific principles
      underlying viral entry and gene expression into specific populations of renal
      cells will facilitate the design of successful therapeutic viral-based gene
      transfer strategies.

PMID- 11841606
TI  - Recent advances in recombinant adeno-associated virus vector production.
AB  - Adeno-associated virus (AAV) is a replication-defective parvovirus that is being
      developed as a vector for human gene transfer. Recombinant AAV (rAAV) vectors are
      being proposed as a gene transfer vehicle for an array of human diseases. The
      recent interest in rAAV has been driven by the unexpected finding that these
      simple vectors can efficiently transduce a variety of postmitotic cells,
      resulting in long-lived, robust gene expression. However, a major obstacle to
      commonplace usage of rAAV vectors was the production in sufficient quantities for
      preclinical and human trials. Fortunately, several recent technological advances
      in vector production, purification, and titration have resulted in significant
      increases (>10-fold) in production capacity. Thus, there are several methods for
      the production of rAAV in excess of 10(4) particles/cell, levels that should
      permit widespread use of this technology for clinical applications.

PMID- 11841607
TI  - Adenovirus-mediated gene transfer to renal glomeruli in rodents.
AB  - BACKGROUND: The expression of foreign genes into renal glomerular cells holds
      enormous potential to modulate the outcome of renal diseases. Recombinant
      adenoviruses (rAds) are promising gene transfer vectors because they have the
      ability to infect a wide range of nondividing cells. However, despite the fact
      that renal glomeruli are easily accessible via the renal circulation, adenovirus
      mediated gene transfer into rodent glomeruli has been problematic. Here, we
      described our experience using rAd vectors to express foreign genes in rodent
      renal glomeruli in vivo and in cultured human renal glomerular cells. METHODS: We
      developed two techniques--the "portal clamping" and "prolonged renal infusion"-
      to infect mouse and rat renal glomeruli in vivo, respectively. We used E-1
      deleted rAd vectors carrying the lacZ gene encoding beta-galactosidase (Ad.
      CBlacZ) under the control of the cytomegalovirus enhancer and chicken beta-actin
      promoter. Cultured human renal glomerular podocytes, endothelial and mesangial
      cells were grown following standard techniques. Transgene expression was
      evaluated by doing beta-galactosidase staining and reverse transcription
      polymerase chain reaction studies. RESULTS: We found that both a prolonged
      exposure and a high concentration of circulating adenoviral vectors were required
      to achieve efficient gene transfer to renal glomerular cells in rodents. The
      virus-mediated transgene expression in renal glomeruli lasted for at least 42
      days in mice and 21 days in rats without causing significant renal injury.
      CONCLUSIONS: These data demonstrate the feasibility of using rAd vectors as a
      tool to express foreign genes in rodent renal glomerular cells and suggest that
      all types of human renal glomerular cells are equally susceptible to rAd
      infection.

PMID- 11841608
TI  - New generation adenoviral vectors improve gene transfer by coxsackie and
      adenoviral receptor-independent cell entry.
AB  - Adenoviral (Ad) vectors possess many attributes that have lead to their use as
      gene delivery agents in human clinical trials. However, gene transfer efficiency
      has generally been less than that needed for meaningful clinical responses. The
      restricted tropism of the virus for its native receptor, the coxsackie and
      adenoviral receptor (CAR), is emerging as a key limitation to the use of these
      agents. By developing strategies to achieve Ad infection via alternate receptor
      pathways, enhanced and more specific gene delivery can be achieved. This new
      generation of tropism-modified agents holds promise for the improved clinical
      utility of Ad vectors for gene therapy.

PMID- 11841609
TI  - In vivo gene transfer to kidney by lentiviral vector.
AB  - BACKGROUND: The growing understanding of the molecular basis of renal diseases
      makes the development of gene therapy for kidney disorders a potential treatment
      alternative. Work aimed at determining the feasibility and the efficiency of gene
      transfer to the kidney using different viral and nonviral transduction systems is
      a necessary component to understanding the full potential. Lentiviral vectors
      have been shown to transduce stably different tissues and cell types that are
      refractory to other gene transfer approaches. To date, the potential of
      lentiviral vectors to transfer genes in kidney has not been investigated. The
      scope of this work was to analyze the efficiencies of in vivo transduction of
      kidney by a lentiviral vector. METHODS: A pseudotyped lentiviral vector carrying
      the gene for the enhanced green fluorescent protein (EGFP) was delivered into one
      kidney of experimental mice by retrograde infusion through the ureter. The
      presence of the virus and the expression of the reporter protein were monitored
      over time. RESULTS: Both viral DNA and EGFP expression were measurable in the
      kidney infused with the lentiviral vector but not in the contralateral kidney.
      Protein expression was detected by immunostaining, as EGFP fluorescence was
      masked by the high background fluorescence of the kidney. Expression of EGFP
      persisted for the entire two-month duration of the experiments. CONCLUSIONS:
      Lentiviral vectors can effectively deliver exogenous genes to the kidney in vivo,
      resulting in persistent expression of the introduced gene.

PMID- 11841610
TI  - Gene electrotransfer: potential for gene therapy of renal diseases.
AB  - The ability to pursue gene therapy has been limited by the availability of an
      effective and safe system for gene delivery, especially to the kidney.
      Electroporation is an efficient method to transfer physiologically the gene to
      the cells without complicated preparation. Given that the systemic delivery of
      the functional protein can serve for the therapy of the renal diseases, skeletal
      muscle targeting gene therapy might be an alternative strategy for treatment of
      renal disease. Gene therapy to the transplant kidney may potentially improve the
      graft outcome by reducing acute and chronic rejections. We review on an emerging
      strategy of gene electrotransfer and discuss the potential application of gene
      therapy to renal diseases.

PMID- 11841611
TI  - Targeted adenoviral gene transfer to the kidney.

PMID- 11841612
TI  - Chimeric RNA/DNA oligonucleotide-based gene therapy.
AB  - BACKGROUND: Chimeric RNA/DNA oligonucleotides, emerging as a potential strategy
      for gene therapy, have been shown to induce site-specific correction of point
      mutations in several genetic disease models. METHODS: Six recent studies of
      chimeric RNA/DNA oligonucleotide-based gene therapy in genetic disease models are
      reviewed. Chimeric RNA/DNA oligonucleotides, complementary to 25 to 30 residues
      of genomic DNA flanking the mutation site with the exception of a mismatch in the
      center, were delivered via different routes and delivery vehicles to target
      different tissues and organs. Corrections of the mutation at genotypic and
      phenotypic levels were assessed using various methods, including allele-specific
      polymerase chain reaction assay, restriction enzyme digestion, colony-lifting
      assays, sequencing, Northern and Western blot analyses, enzyme activity assay,
      immunohistochemical staining, and functional studies. RESULTS: The gene
      correction frequency varied, ranging from less than 1% to more than 40%. This
      represented several magnitudes higher conversion rate compared with homologous
      recombination frequency, which is in the range of 10(-5) to 10(-6). The resulting
      phenotype changes lasted longer than one year in some studies. CONCLUSION:
      Chimeric RNA/DNA oligonucleotide-based gene therapy has the potential to develop
      into powerful therapeutic modality for genetic diseases. It can offer permanent
      expression and normal regulation of corrected genes in appropriate cells or
      tissues. Further efforts to elucidate the mechanisms of chimeric RNA/DNA
      oligonucleotide-based gene therapy are warranted in order to increase the
      efficacy and safety of this method.

PMID- 11841613
TI  - Polarity of alpha-galactosidase A uptake by renal tubule cells.
AB  - BACKGROUND: Congenital absence of alpha-galactosidase in Fabry disease leads
      eventually to renal failure. Fabry disease is an attractive candidate for gene
      therapy, but uptake mechanisms of the enzyme must be understood for it to be used
      in treating patients with Fabry disease. METHODS: Immortalized human renal
      epithelial cells from three regions of the tubule were grown in culture on
      collagen-coated Transwell filters and were incubated with recombinant alpha
      galactosidase protein placed at either the luminal or basolateral side of the
      cells. Uptake into cells was measured, and kinetic studies were performed.
      Blocking experiments were done with mannose 6-phosphate. RESULTS: Uptake from the
      basolateral side of the filters predominated in all three cell types. Only in
      distal tubule cells was mannose 6-phosphate able to block uptake to any degree.
      The kinetic data reveal a high Km for both luminal and basolateral cell surfaces.
      CONCLUSIONS: These data suggest that to correct the renal phenotype in Fabry
      disease, high levels of the enzyme will be need to be delivered to kidney cells.
      This will likely best be achieved with local administration of a vector
      containing the transgene directly to the kidney.

PMID- 11841614
TI  - Gene therapy and solid-organ transplantation.
AB  - Recent developments in transplantation medicine improved the short- and long-term
      survival of solid-organ transplantation. However, chronic allograft rejection,
      the side effects of the long-term immunosuppressive treatment, and organ shortage
      are still the major obstacles to achieving long-term survival. Gene therapy has
      the potential to meet these challenges and has unique advantages in
      transplantation. In this review we summarize the studies using gene therapy in
      solid-organ transplantation.

PMID- 11841615
TI  - Approaches to understanding susceptibility to nephropathy: from genetics to
      genomics.
AB  - The incidence of end-stage renal disease (ESRD) is increasing worldwide despite
      efforts to slow the progression of chronic renal failure (CRF) by controlling
      blood pressure and hyperglycemia. Two available therapies for ESRD, dialysis and
      transplantation, are expensive and are at best palliative. Recently, data from
      several laboratories have demonstrated that ESRD is under substantial genetic
      control, and efforts to identify these genetic determinants are underway.
      Identifying genes for ESRD pathogenesis has several goals. First, understanding
      the genetic basis of ESRD offers a means to clarify the mechanisms that result in
      kidney pathobiology. Second, better and new treatments for prevention of
      progression of CRF to ESRD may be developed. Third, individuals at risk could be
      identified early in their course and targeted for intensive therapy. Finally, the
      products of genes causing disease become target molecules for gene therapy. In
      this article, we discuss data from our laboratories, which employ two different
      molecular genetic strategies for identifying ESRD pathogenesis genes. In contrast
      to traditional experimental design, both approaches are hypothesis generating,
      identifying candidate molecules for further study, rather than hypothesis driven
      and may provide novel insights into mechanisms of renal disease progression.

PMID- 11841617
TI  - Gene expression and identification of gene therapy targets in diabetic
      nephropathy.
AB  - A number of novel genes that are up-regulated in diabetic kidneys have been
      identified. Recently, transforming growth factor-beta (TGF-beta)--driven secreted
      proteins, i.e., connective tissue growth factor (CTGF) and gremlin, were
      identified. They are up-regulated in kidneys of diabetic animals and modulate the
      biology of mesangial cells. CTGF mediates TGF-beta--induced matrix overproduction
      by the mesangial cells. Gremlin is a putative antagonist of bone morphogenetic
      protein-2 that blocks mesangial cell proliferation. Thus, gremlin may modulate
      the biology of mesangium by stimulating mesangial cell proliferation and in turn
      production of matrix. In addition, transcriptionally regulated kinases, serum
      glucocorticoid-regulated kinase and munc-13 have been identified. The former
      stimulates renal tubular Na+ transport and is involved in hyperfiltraion of
      diabetic kidneys by a Na+ transport feedback mechanism. Munc-13 has been shown to
      induce apoptosis in hyperglycemic state via diacylglycerol-activated, PKC
      independent signaling pathway. Another pathway relevant to diabetic nephropathy
      is polyol pathway, where glucose is reduced to sorbitol by aldose reductase.
      Recently, a renal-specific reductase of the aldo-keto reductase family was
      isolated. It is up-regulated in diabetic mice, and this could serve as a suitable
      target for gene therapy in renal complications of diabetes. Several mitochondrial
      genome-encoded genes, such as, cytochrome oxidase and NADH dehydrogenase, are up
      regulated in diabetic kidneys. A novel nuclear-encoded mitochondrial gene, i.e.,
      translocase inner mitochondrial membrane 44 (Tim44), is up-regulated in diabetic
      kidneys, and it may also serve as another target for molecular therapeutic
      intervention at the core storage energy sites, i.e., mitochondria. In this
      review, these novel differentially regulated genes that respond to hyperglycemic
      stress are described, and they may serve as possible targets for gene therapy in
      the treatment of diabetic nephropathy.

PMID- 11841616
TI  - Glomerular beta-galactosidase expression following transduction with microsphere
      adenoviral complexes.
AB  - The aortic injection of adenoviral-microsphere complexes is a useful technique
      for in vivo gene transfer (transduction) to the glomerulus. In this approach, the
      appearance of the foreign transprotein in the glomerulus may result from
      glomerular cell gene transfer and local synthesis or hepatic cell transduction
      followed by synthesis, secretion, and deposition in the glomerulus. We postulated
      that glomerular expression of the foreign transgene was the result of glomerular
      cell transduction. To test this question, male SD rats underwent aortic
      injections with adenovirus containing the LacZ expression cassette [expressing
      beta-galactosidase (betagal)] coupled to 16 microm diameter microspheres. After
      48 hours, histologic staining confirmed glomerular expression of the betagal
      transprotein and reverse transcription in situ polymerase chain reaction
      demonstrated the presence of the betagal transgene in the glomerulus. In
      addition, hepatic expression of the betagal transprotein was minimal and
      substantially less than that observed in the glomeruli. These data support the
      contention that adenoviral-microsphere complexes result in glomerular cell
      transduction with the desired transgene, followed by local transprotein
      synthesis. This approach may prove useful for facilitating glomerular gene
      transfer in the development of gene therapy for glomerulonephritis.

PMID- 11841618
TI  - Cytoprotection of pancreatic islets before and early after transplantation using
      gene therapy.
AB  - Pancreatic islet transplantation (PIT) is an attractive alternative to insulin
      dependent diabetes treatment but is not yet a clinical reality. The first few
      days after PIT are characterized by substantial pancreatic islet dysfunction and
      death. Apoptosis has been documented in PI after extracellular matrix removal,
      during culture time, after exposure to proinflammatory cytokines, hypoxic
      conditions before islet revascularization, and rejection. Targeting the apoptosis
      pathway by adenoviral-mediated gene transfer of the anti-apoptotic Bcl-2 gene
      exerts a major cytoprotective effect on isolated macaque pancreatic islets. Bcl-2
      transfection ex vivo protects islets from apoptosis induced by disruption of the
      islet extracellular matrix during pancreatic digestion. Additionally, over
      expression of Bcl-2 confers long-term, stable protection and maintenance of
      functional islet mass after transplantation into diabetic SCID mice. Genetic
      modification of PI also reduced the islet mass required to achieve stable
      euglycemia. Ex vivo gene transfer of anti-apoptotic genes has potential as a
      therapeutic approach to both minimize loss of functional islet mass post
      transplant and reduce the high islet requirement currently needed for successful
      stable reversal of insulin-dependent diabetes [1, 2].

PMID- 11841619
TI  - New intra-renal graft genes associated with tolerance or rejection.
AB  - BACKGROUND: Recipient type mononuclear cells infiltrating kidney allografts have
      different phenotypes and functions according to the fate of the graft. We
      hypothesized that different genetic programs were involved in rejected or
      accepted tissues and thus, transcripts that correlated with the clinical status
      could be identified by a differential expression strategy. This strategy was
      applied to miniature swine class II matched, class I disparate kidney grafts,
      which are accepted in recipient animals treated for 12 days with Cyclosporin A
      (CsA). METHODS: The mRNA differential display RT-PCR technique (DDRT-PCR) was
      used to detect clinical status-specific transcripts. cDNA templates for this
      analysis were derived from biopsies of accepted (CsA treated) and rejected
      (untreated) kidney grafts 8 days post-transplantation. RESULTS: A first screening
      procedure identified 23 PCR products differentially amplified in either tolerant
      or rejector samples. Nucleotide sequence of these partial transcripts showed that
      11 out of 23 (48%) sequences had unknown open reading frames while 12 had
      substantial homology to known sequences. To validate the approach, rejection
      associated (RA) cDNA 1 (RA-1) was characterized further. The results indicated
      that RA-1 is the porcine equivalent of secreted protein acidic and rich in
      cysteine (SPARC). Expression studies demonstrated that upregulation of SPARC gene
      transcription preceded other indicators of kidney dysfunction and correlated with
      the extent of graft infiltration. CONCLUSION: DDRT-PCR appears to be a powerful
      technique to identify genes differentially expressed in grafted tissues that
      correlate with tolerance or rejection. One of the gene transcripts identified
      through this method, SPARC, may be a reliable marker of tissue injury consequent
      to cellular infiltration and rejection.

PMID- 11841620
TI  - Gene transfer of Smad7 using electroporation of adenovirus prevents renal
      fibrosis in post-obstructed kidney.
AB  - BACKGROUND: Unilateral ureteral obstruction (UUO) leads to interstitial fibrosis
      of the obstructed kidney, and TGF-beta is considered to play an important role in
      this fibrotic process. Smad7 has been recently identified as an antagonist of TGF
      beta signaling. To investigate whether this novel molecule can be exploited for
      therapy of renal fibrosis, we determined the effect of exogenous Smad7,
      introduced by a recombinant adenovirus vector combined with in vivo
      electroporation (EP), on UUO-induced renal fibrosis in rats. METHODS: A model of
      UUO was made in SD rats by ligating their left ureters. The next day, the rats
      were divided into four groups and adenovirus was injected into the extended
      pelvic space (two groups received AdCMV-LacZ and two groups received AdCMV
      Smad7). Then, EP was performed in one group of AdCMV-LacZ-injected rats and one
      group of AdCMV-Smad7-injected rats. The renal tissues were obtained 3, 5, 10, and
      14 days after the UUO operation. We detected the efficiency of transgene by
      immunoblots of renal cortical and medullary tissues and immunohistochemical
      studies for Smad7 and FLAG (the FLAG gene was introduced in the AdCMV-Smad7 as a
      marker). The renal fibrosis was monitored by histological scoring of Masson
      stainings. RESULTS: In immunoblotting, both Smad7 and FLAG were clearly detected
      in the renal medullary tissue of the rats given AdCMV-Smad7 with EP. In contrast,
      immunoblots of renal cortical tissue did not demonstrate positive bands. In
      immunohistological study, Smad7 was stained in the renal medulla in the rats
      given AdCMV-Smad7 with EP. In the rats given AdCMV-Smad7 without EP, only a weak
      signal was detected in renal medullary tissue. The rats given AdCMV-Smad7 with EP
      demonstrated significantly more suppression of renal fibrosis than rats treated
      with AdCMV-LacZ. The rats treated with AdCMV-Smad7 without EP did not demonstrate
      significant suppression of renal fibrosis. CONCLUSION: These data indicate that
      gene transfer of Smad7 prevents UUO-induced renal fibrosis, suggesting that Smad7
      may be applicable for the treatment of renal fibrosis. In vivo electroporation of
      adenovirus may be a powerful tool for gene delivery in renal tissue.

PMID- 11841621
TI  - Emerging targets: molecular mechanisms of cell contact-mediated growth control.
AB  - Contact inhibition of cell proliferation evokes a unique cellular program of
      growth arrest compared with stress, age, or other physical constraints. The last
      decade of research on genes activated by cell-cell contact has uncovered features
      of transmembrane signaling, cytoskeletal reorganization, and transcriptional
      control that initiate and maintain a quiescent phenotype. This review will focus
      on mechanisms controlling contact inhibition of cell proliferation, highlighting
      specific gene expression responses that are activated by cell-cell contact.
      Although a temporal framework for imposition of these mechanisms has not yet been
      well described, contact inhibition of cell proliferation clearly requires their
      coordinated function. Novel targets for intervention in proliferative disorders
      are emerging from these studies.

PMID- 11841622
TI  - Effects of amino acids and glucose on mesangial cell aminopeptidase a and
      angiotensin receptors.
AB  - BACKGROUND: High protein diets and diabetes increase renal renin angiotensin
      system (RAS) activity, which is associated with glomerular injury. Aminopeptidase
      A (APA) is a cell surface metalloprotease that degrades angiotensin II (AII) in
      the mesangium. Mesangial cells (MC) also possess receptors for AII; the type 1
      (AT1 receptor) promotes proliferation and fibrosis, while the type 2 (AT2
      receptor) opposes these effects. We evaluated whether amino acids and glucose
      alter expression of APA, AT1 receptor and AT2 receptor in a manner that further
      augments RAS activity. METHODS: Confluent rat MC were grown in serum-free media
      for 48 hours prior to exposing to experimental conditions: control (C), high
      amino acids (HA, mixed amino acid solution added to raise concentrations 5- to 6
      fold over C), high glucose (HG 30, mM glucose). Semi-quantitative RT-PCR was used
      to assess mRNA for APA, AT1 receptor, AT2 receptor, and beta-actin. Values are
      expressed relative to beta actin. RESULTS: Both HA and HG reduced APA mRNA (HG
      1.13 plus minus 0.19, HA 1.12 plus minus 0.16 versus C 1.27 plus minus 0.16 P <
      0.05, N = 8). HA increased AT1 receptor mRNA (HA 2.11 plus minus 0.43 versus C
      1.14 plus minus 0.28 P < 0.05, N = 8). HG increased AT2 receptor mRNA (HG 1.31
      plus minus 0.43 versus C 0.82 plus minus 0.33 P < 0.05, N = 6). CONCLUSIONS: A
      reduction of APA, in response to high levels of amino acids or glucose, could
      contribute to increased AII as a result of decreased degradation in MC. The
      effect of amino acids to increase AT1 receptor expression may further enhance
      adverse hemodynamic and pro-fibrotic actions of AII. Conversely, glucose
      increased AT2 receptor expression, which could modulate responses mediated by the
      AT1 receptor.

PMID- 11841623
TI  - Angiogenic gene therapy: pre-clinical studies and phase I clinical data.
AB  - Over the last three decades, significant progress has been made in the management
      of patients with atherosclerotic coronary and peripheral vascular diseases using
      medical, surgical, and percutaneous therapies. Despite these advances, there
      remains a significant population of patients who are not optimal candidates for
      surgical or percutaneous revascularization. These patients continue to suffer
      from the debilitating symptoms of their disease and remain at risk for myocardial
      infarction, limb loss, or death. It was this clinical need, coupled with the
      advances in the understanding of angiogenesis, that has led to efforts to develop
      angiogenic therapies for patients with peripheral and myocardial ischemia. In
      general, these conditions are characterized by local hypovascularity, and the
      approach to treatment is therefore focused on stimulating neovascularization.

PMID- 11841624
TI  - Impediments to successful gene transfer to the kidney in the context of
      transplantation and how to overcome them.
AB  - BACKGROUND: Manipulation of the graft with immunosuppressive genes represents a
      novel approach to overcome the toxicity of immunosuppressants currently used to
      prevent acute rejection. Here we compared the efficiency of a non-viral versus a
      viral technique of gene transfer to the kidney in the setting of
      isotransplantation and evaluated whether transfection with adenovirus encoding
      CTLA4Ig prolonged allograft survival. METHODS: Donor rat kidneys were perfused
      with a medium containing the cationic polymer polyethylenimine PEI 25k complexed
      to a vector coding for the beta-galactosidase (beta-gal) gene or with a
      replication-deficient adenovirus encoding the beta-gal gene (AdCMVbeta-gal; 1 x
      10(9) pfu) before isotransplantation. In another set of experiments, donor
      kidneys were perfused with an adenovirus encoding the murine CTLA4Ig gene
      (AdmCTLA4Ig; 1 x 10(9) pfu) before allotransplantation. RESULTS: Perfusion with
      PEI/DNA complexes resulted in large areas of hypoperfusion, histology showed
      glomerular and tubular injury, capillary thrombosis, and complement activation.
      Reperfusion with lower PEI/DNA ratio was possible but no detectable transfection
      observed. In animals receiving adenovirus, beta-gal activity increased with time
      and localized mainly in proximal and distal tubular cells as documented by beta
      gal histochemistry and in situ hybridization. Adenovirus-mediated transduction of
      CTLA4Ig, a recombinant fusion protein that blocks T cell activation, resulted in
      a prolonged allograft survival. CONCLUSIONS: The toxic effects observed in
      kidneys exposed to PEI 25k prevent any future possibility of their use in
      clinical transplantation. By contrast, adenovirus-mediated gene transfer to the
      kidney offers exciting perspectives for the future of transplant medicine.
      Transducing the graft with a gene encoding CTLA4Ig effectively prolongs renal
      graft survival and induces sustained unresponsiveness to the donor antigens
      without the need of immunosuppression.

PMID- 11841625
TI  - Aquaporin gene delivery to kidney.
AB  - BACKGROUND: Several aquaporin- (AQP) type water channels are expressed in kidney
      tubules and microvessels, including AQP1 in proximal tubule, thin descending limb
      of Henle and vasa recta, AQP2 in collecting duct apical membrane, and AQP3 and
      AQP4 in collecting duct basolateral membrane. Mice deficient in these aquaporins
      have distinct phenotypic abnormalities. AQP1 null mice are polyuria and unable to
      generate a concentrated urine after water deprivation. AQP2-T126M mutant mice and
      AQP3 null mice manifest nephrogenic diabetes insipidus (NDI) with severe
      polyuria, whereas AQP4 null mice have only a mild defect in maximal urinary
      concentrating ability. We reasoned that these mice could serve as useful models
      for gene replacement because of their predictable and unambiguous phenotypes.
      METHODS: In an initial feasibility study, an adenovirus directing the expression
      of AQP1 was introduced into AQP1 null mice by intravenous infusion. RESULTS: At 1
      week after adenovirus infusion, AQP1 was seen in many proximal tubules and
      microvessels. Compared with untreated null mice, the treated mice were able to
      partially concentrate their urine and lost less weight after water deprivation.
      However, AQP1 transgene expression and functional correction were lost over 3-5
      weeks. CONCLUSION: Although there remain many technical problems to overcome,
      aquaporin gene replacement has potential applications in hereditary and acquired
      NDI, and in the transient modulation of renal fluid conservation.

PMID- 11841626
TI  - c-myc antisense oligonucleotide treatment ameliorates murine ARPKD.
AB  - BACKGROUND: Overexpression of c-myc is postulated to play a role in the
      pathogenesis of polycystic kidney disease (PKD). c-myc expression is increased in
      all rodent models of PKD that have been examined as well as in human ADPKD. To
      determine whether overexpression of renal c-myc contributes to renal cyst
      formation, C57BL/6J-cpk litters (an animal model of ARPKD) were treated with an
      antisense oligomer (ASO) to c-myc mRNA. METHODS: Injections of 30 microg of a c
      myc ASO were given to C57BL/6J-cpk litters on postnatal days 7-20. Control mice
      received either sham injections or injections of an equal amount of a scrambled
      ASO. At 20 days, kidney weight, body weight, serum urea nitrogen (SUN),
      hematocrit, and renal concentration of ASO were determined. In kidney, c-Myc and
      PCNA protein were assessed by immunoblotting and steady state levels of renal RNA
      for c-myc, EGF, SGP-2, and histone H4 were assessed by northern blot
      hybridization. c-Myc and PCNA proteins were localized by immunohistochemistry.
      RESULTS: Cystic mice treated with the c-myc ASO had a decreased relative kidney
      weight, improved renal function, and a reduced amount of cystic change compared
      with sham and scrambled ASO controls. The abnormal expression of several PKD
      related proteins and mRNAs were partially reversed by c-myc antisense treatment.
      c-myc staining appeared to be reduced in the noncystic tubules. Treatment with
      the c-myc ASO did not cause a reduction in hematocrit or total body weight
      indicating that the beneficial effects were not due to a generalized inhibition
      of cell proliferation in rapidly growing tissue. CONCLUSIONS: c-Myc appears to
      play a role in the cystogenesis of cpk-induced murine PKD and antisense targeting
      the overexpression of c-myc partially ameliorated the renal changes.

PMID- 11841627
TI  - Impaired endocytosis may represent an obstacle to gene therapy in polycystic
      kidney disease.
AB  - BACKGROUND: Autosomal-dominant polycystic kidney disease (ADPKD) is the most
      common hereditary renal disease and a frequent cause of chronic renal failure.
      The cloning of the PKD1 and PKD2 genes, which are mutated in the great majority
      of patients with this disease, opens up the opportunity for somatic gene therapy
      by introduction of the wild-type gene or cDNA. Several publications have provided
      evidence, that many portions of the nephron and the collecting duct can form
      cysts, including the proximal tubule. Alterations in the proximal tubule may
      prevent the efficient endocytosis of filtered proteins and thus contribute to
      proteinuria, a frequent symptom in patients with polycystic kidney disease. At
      the same time this may also negatively affect various gene therapy strategies,
      since endocytosis is important for the uptake of foreign DNA at least under some
      circumstances. In the (cy/+) rat, a widely used animal model for ADPKD, cysts
      almost exclusively develop from proximal tubules, and we have therefore
      investigated whether proteinuria and defective endocytosis also occur in this
      model. METHODS: Proteinuria was demonstrated by direct measurement and by protein
      gel electrophoresis of urines from 16 week-old (cy/+) rats. Endocytosis was
      investigated by injection of FITC-dextran and immunohistochemical staining with
      anti-ClC-5 and anti-megalin antibodies. RESULTS: Similar to the observations made
      in ADPKD patients, proteinuria also develops in the (cy/+) rat. Using FITC
      labeled dextran as an in vivo tracer for renal tubular endosomal function, we
      could show that portions of cyst-lining epithelia from proximal tubules have lost
      the ability to endocytose, which is necessary for the reabsorption of albumin and
      lower-molecular-weight proteins. By immunohistochemistry the expression of other
      proteins implicated in endocytosis, such as the chloride channel ClC-5 and the
      albumin receptor megalin, correlated well with the presence and absence of FITC
      dextran in cyst wall epithelia. CONCLUSION: These data indicate that proteinuria
      and albuminuria in the (cy/+) rat model for ADPKD are due to a loss of the
      endocytic machinery in epithelia of proximal tubular cysts. Such a defect may
      also reduce the efficacy of certain gene therapy protocols.

PMID- 11841628
TI  - Tinea capitis in infants less than 1 year of age.
AB  - Tinea capitis is the most frequent manifestation of dermatophyte infection in
      children, but because it is rare in the first months of life it is often
      misdiagnosed. Here we report 15 cases of tinea capitis observed in Italy in
      infants less than 1 year of age. There were 10 boys and 5 girls (mean age 6
      months). Diagnosis was confirmed by mycologic examination. Microsporum canis was
      isolated in nine cases and Trichophyton mentagrophytes in three. These 12 infants
      were Italian and animals were the source of infection. Trichophyton erinacei was
      isolated in one Italian infant, and the source was soil. In the other two cases,
      Trichophyton tonsurans and Trichophyton violaceum were isolated; these infants
      were from Central America and India, respectively, and had contracted the
      infection from humans. All achieved clinical and mycologic recovery after
      systemic and topical antimycotic therapy.

PMID- 11841629
TI  - Dermatosurgery using subcutaneous infusion anesthesia with prilocaine and
      ropivacaine in children.
AB  - Pediatric surgical procedures under local anesthesia have been limited by the
      pain of injections and, because of low body weight, rapidly reached maximum
      doses. In subcutaneous infusion anesthesia (SIA) highly diluted local anesthetics
      are administered by flow- and volume-controlled infusion pumps. This article
      presents a retrospective review of the use of SIA in children undergoing excision
      of dermatologic problem lesions. A total of 354 surgical procedures,
      predominantly excisions of nevi in 271 children (3 months-16 years) were
      performed in 1999: 67 children were operated on under general anesthesia and 204
      children with local anesthesia. For local anesthesia we used SIA with diluted
      prilocaine and ropivacaine (equivalent mixtures of 0.3%, 0.15%, 0.08%). The 67
      children operated on under general anesthesia were younger (mean age 3.05 +/-
      2.93 years, median age 2.00 years) than the 204 children who had surgery with SIA
      (mean age 9.00 +/- 4.2 years, median age 9.00 years). The sizes of excisions
      under general anesthesia were larger (maximum 1060 cm2, mean 76 +/- 225 cm2,
      median 7 cm2) than those under SIA (maximum 628 cm2, mean 22 +/- 100 cm2, median
      3 cm2). No side effects of local anesthesia were observed in these pediatric
      procedures. The additional use of ropivacaine resulted in prolonged postoperative
      analgesia. SIA in children is a well-accepted, safe anesthesia that in some cases
      offers an alternative to general anesthesia.

PMID- 11841630
TI  - Parental knowledge and practice of primary skin cancer prevention: gaps and
      solutions.
AB  - Over the past two decades there have been significant efforts in the United
      States to heighten awareness about skin cancer. Our goal was to assess parental
      knowledge, practice, and source of information about sun protection for their
      children. A questionnaire was administered to 158 parents of children at a
      dermatology clinic and 96 parents of children at a pediatric clinic (n=254). The
      survey included four parts: demographics, knowledge about skin cancer, sun
      protection practices, and sources of sun protection information. The mean
      knowledge score was 61% correct. Independent predictors of a higher score were
      fewer children and being a health care or other professional (p < 0.03).
      Independent predictors of parental sunscreen use were higher knowledge score,
      younger age, and fewer lifetime sunburns (p < 0.03); predictors of sunscreen use
      for children were higher knowledge score and fairer skin (p < 0.03). The top
      sources of sun protection information ranked by respondents were television and
      magazines; the top desired sources were primary care physicians and
      dermatologists. The knowledge results suggest the need for increased education
      about skin cancer prevention. Because the media is a major information source, it
      is important to ensure that messages about sun risks/protection are correct. The
      respondents' desire to learn more from primary care physicians emphasizes the
      need to educate physicians about sun protection.

PMID- 11841631
TI  - Atrophia maculosa varioliformis cutis: a pediatric case.
AB  - Atrophia maculosa varioliformis cutis was described in 1918 by Heidingsfeld as a
      type of idiopathic noninflammatory macular atrophy typically occurring in young
      individuals. Only 13 cases have been reported since the first description.
      Considering that atrophia maculosa varioliformis cutis can be mistaken for a
      scarring and artifact dermatitis, it is important for physicians to distinguish
      this condition. We report a new case in a 5-year-old boy.

PMID- 11841632
TI  - Persistent atypical lymphocytic hyperplasia following tick bite in a child:
      report of a case and review of the literature.
AB  - We report a 6-year-old girl who developed a red papule on the posterior neck at
      the site of a previous tick bite. Initial biopsy was performed a year after the
      bite and the specimen showed a dense lymphoid infiltrate with admixed CD30+
      cells. The patient was referred to our center because of concern about the
      development of a CD30+ lymphoproliferative disorder. The lesion was completely
      excised. Histology showed no evidence of a clonal lymphoproliferative disorder or
      Borrelia infection, but persistence of CD30+ cells. This case demonstrates that a
      tick bite reaction can persist for more than 1 year and show immunophenotypic and
      morphologic overlap with a CD30+ lymphoproliferative disorder. Complete history
      with thorough clinical and histopathologic evaluation is necessary to arrive at
      the correct diagnosis.

PMID- 11841633
TI  - Ellis-van Creveld Syndrome: a report of two cases.
AB  - Ellis-van Creveld syndrome (EVC) or chondroectodermal dysplasia, a rare autosomal
      recessive disorder, is a tetrad of chondrodysplasia, ectodermal dysplasia,
      polydactyly, and congenital heart disease, of which chondrodystrophy of the
      tubular bones is the most common feature, while central nervous system (CNS) and
      urinary tract anomalies are some of its rarer associations. This report describes
      EVC syndrome in two sisters of Indian origin, ages 8 and 6 years, the products of
      nonrelated, unaffected parents. The patients had chondrodysplasia of tubular
      bones resulting in disproportionate dwarfism, polydactyly, severely dystrophic
      nails, partially absent teeth, and short and bound-down upper lips with multiple
      frenulae. Other features noted in the girls were syndactyly and mild mitral
      regurgitation. All four of the classic features of EVC syndrome were present in
      patient 1 and three in patient 2. Additional findings were ichthyosis and plantar
      keratoderma in the former and absent clavicles in the latter, which have not been
      reported previously. The importance of prenatal diagnosis of EVC is stressed and
      a multidisciplinary approach for the management of these patients is highlighted.

PMID- 11841634
TI  - Association of piebaldism and neurofibromatosis type 1 in a girl.
AB  - We report an 11-year-old girl with both piebaldism and neurofibromatosis type 1
      (NF1). The patient had large depigmented patches on her lower limbs and a white
      forelock since birth. In addition, some cafe au lait spots were present on her
      trunk at birth and had increased in number and size during childhood in
      concomitance with the appearance of axillary and inguinal freckling. Neither
      neurofibromas nor Lisch nodules were detected and the patient was otherwise
      healthy. Pedigree analysis revealed inheritance for piebaldism on the paternal
      side. To our knowledge, the association of piebaldism and NF1 has been described
      previously in only three patients. Awareness of this rare association is relevant
      to ensure early diagnosis and adequate follow-up for NF1.

PMID- 11841635
TI  - Multiple agminated Spitz nevi arising on a cafe au lait macule: review of the
      literature with contribution of another case.
AB  - The majority of Spitz nevi are acquired solitary lesions. Multiple Spitz nevi are
      rare and may develop on hyperpigmented skin. We report a 16-year-old girl with
      multiple Spitz nevi arranged on a cafe au lait macule. Immunohistochemistry
      showed positivity for S-100 and HMB-45. Of interest, expression of Polo-like
      kinase (PLK), a novel proliferation marker that recently proved to be positive in
      up to 98% of malignant melanoma cells, showed positivity in 40% of the nevus
      cells. The clinical development of multiple Spitz nevi is not yet clear, as they
      are preferentially excised. Reviewing 70 cases in the literature we found that
      multiple agminated Spitz nevi occur more frequently than reported previously. In
      about one-third of these cases Spitz nevi arose on congenitally hyperpigmented
      skin.

PMID- 11841636
TI  - The first case of exophytic pilomatricoma in an Asian male.
AB  - Pilomatricomas are benign cutaneous neoplasms that occur frequently in children
      and usually present as slow-growing, firm, dermal nodules. They are the second
      most common skin lesion excised from children. A rare exophytic variety has been
      described, but to our knowledge this has not previously been reported in Asian
      children. We present this case to highlight the clinical features and to affirm
      that race may not play a role in the etiology of pilomatricomas. We also
      illustrate how these lesions can be effectively treated by shave excision.

PMID- 11841637
TI  - New-onset ichthyosis and diabetes in a 14-year-old.
AB  - Diabetes has not been linked to acquired ichthyosis or ichthyosis vulgaris. We
      report a newly diagnosed diabetic 14-year-old girl with bilateral tibial and
      sacral ichthyosiform plaques and a hemoglobin A1c of 20.1%. The patient had no
      personal or family history of atopy or ichthyosis and lacked keratosis pilaris or
      hyperlinear palms. A biopsy specimen of an ichthyosiform plaque showed compact
      lamellar orthohyperkeratosis and hypogranulosis, histopathology consistent with
      either ichthyosis vulgaris or acquired ichthyosis. We speculate that our
      patient's new-onset diabetes induced acquired ichthyosis.

PMID- 11841638
TI  - Infantile McCune-Albright syndrome.
AB  - McCune-Albright syndrome is a rare disorder caused by an activating mutation of
      the alpha subunit of the Gs protein and is characterized by multiple hormonal
      abnormalities, fibrous dysplasia of bone, and cutaneous pigmentation. We report a
      10-week-old infant with McCune-Albright syndrome. He presented with failure to
      thrive, cardiorespiratory distress, and pigmented macules on his face, trunk, and
      limbs. Following the clinical diagnosis of McCune-Albright syndrome, he was
      subsequently shown to have hypercortisolism and hyperthyroidism.

PMID- 11841640
TI  - Lymphangioma circumscriptum treated with pulsed dye laser.
AB  - Lymphangioma circumscriptum is a lymphatic malformation that involves the skin
      and may extend to subcutaneous tissue and muscle. Treatment of these lesions is
      challenging. Surgical excision may be performed but recurrence is common. Herein
      we report a child with a symptomatic lymphangioma circumscriptum that was treated
      with pulsed dye laser with good results. For superficial lymphatic malformations
      containing blood, pulsed dye laser might be considered as a treatment option.

PMID- 11841639
TI  - Guttate psoriasis following Kawasaki disease.
AB  - Guttate psoriasis developed in a 3.5-year-old boy during the course of Kawasaki
      disease (KD). The pathogenesis of this unusual complication may be production of
      superantigens, which is also considered to be a cause of KD.

PMID- 11841641
TI  - Aplasia cutis congenita in surviving co-twins: four unrelated cases.
AB  - Four unrelated patients born from twin pregnancies and showing extracranial
      aplasia cutis congenita are reported. All the patients lost their co-twins during
      the first half of the pregnancy. Two of the patients had the characteristic
      truncal and symmetrical type of aplasia cutis associated with fetus papyraceus
      and placental abnormalities. The presence of multiple hepatic hematomas in one of
      them gives further credit to a "vascular disruption" as the possible pathogenetic
      mechanism of the disorder. The two other patients were born with symmetrical
      aplasia cutis at the extensory aspects of both knees, which presumably represents
      a milder expression of the former defect. Thus the so-called aplasia cutis with
      fetus papyraceus shows heterogeneity in localization, extension, presence of
      extracutaneous abnormalities, and possible association with fetus papyraceus at
      birth. To include all the patients affected by this peculiar type of aplasia
      cutis congenita, the designation of aplasia cutis with extracranial symmetrical
      involvement is proposed.

PMID- 11841642
TI  - Gianotti-Crosti syndrome preceded by oral polio vaccine and followed by varicella
      infection.
AB  - Gianotti-Crosti syndrome (papular acrodermatitis of childhood) is considered a
      nonspecific cutaneous host response to a variety of infectious agents,
      particularly viruses. Herein we report a case of Gianotti- Crosti syndrome
      preceded by oral polio vaccine and followed by varicella infection. The present
      case may support the hypothesis of initial immunization and following viral
      infection as a possible mechanism for Gianotti-Crosti syndrome.

PMID- 11841643
TI  - Itraconazole is effective in the treatment of tinea capitis caused by Microsporum
      canis.
AB  - Tinea capitis is a relatively common superficial fungal infection in children
      which requires oral antifungal therapy. In a prospective, open study over 24
      weeks, itraconazole 5 mg/kg/day, given as capsules or as an oral suspension for a
      period of 2-12 weeks, was used to treat children 1-12 years of age who had M.
      canis tinea capitis. Children with mycologic evidence of M. canis tinea capitis
      were entered into the study and asked to return at week 2 and then every 2 weeks
      thereafter until cured, with a maximum of 12 weeks of active treatment. At each
      visit the scalp was sampled and the material processed for light microscopy and
      culture examination. An extra 2 weeks of itraconazole was prescribed if the
      mycology from the sample obtained on the previous visit indicated that there was
      still presence of the organism. Patients were administered either 2, 4, 6, 8, 10,
      or 12 weeks of treatment. The final follow-up visit was at 12 weeks from the
      cessation of drug therapy. Laboratory blood testing was performed only if
      indicated by history, examination, or the development of side effects. There were
      107 patients (49 boys, 58 girls; mean +/- standard error =5.6 +/- 0.2 years).
      Thirteen of the 107 children were given the oral suspension. At week 12 from the
      cessation of treatment there was complete (clinical and mycologic) cure in all
      107 children. Increasing age of the patient correlated significantly with the
      length of itraconazole capsule therapy (p=0.03). The duration of itraconazole
      treatment also correlated significantly with the severity of tinea capitis at
      baseline (p=0.02). Adverse effects were observed in 5 children receiving
      itraconazole capsules (n=94). These were regarded as being possibly or probably
      due to the drug in two children (mild transient stomach ache in one and moderate
      diarrhea in one). The child with diarrhea stopped therapy at week 4 with complete
      resolution of symptoms. One of 13 children receiving the oral suspension had
      mild, transient diarrhea. There were no drop-outs in this group. Laboratory
      testing was not required in any patient. Compliance was very good in the patient
      group. Itraconazole 5 mg/kg/day given either as a capsule or an oral suspension
      for 4-8 weeks is effective and safe in the treatment of tinea capitis caused by
      M. canis.

PMID- 11841644
TI  - The true and the false: pixel-byte syndrome.
AB  - The possible use of retouched images for fraudulent purposes in scientific
      articles, posters, and conferences is not a future but a present possibility
      (probably already used) that poses serious questions as to the need for
      additional control mechanisms other than scientific peer quality review in
      evaluating and accepting articles. We propose the term "pixel-byte syndrome" to
      illustrate how easy it might be to electronically create a new syndrome for
      fraudulent purposes. The aim of this article is to stimulate discussion among
      professionals, add some examples of easy-to-realize frauds and sow the seeds of
      doubt in the minds of some of the referees of journal articles and the scientific
      secretariat of congresses in reviewing digitally retouched images.

PMID- 11841645
TI  - Subcutaneous infusion anesthesia for dermatologic surgery in children: are we
      ready?

PMID- 11841646
TI  - What syndrome is this? Gingival fibromatosis-hypertrichosis syndrome.

PMID- 11841647
TI  - Grouped vesicular lesions on the abdomen of a 12-year-old girl.

PMID- 11841648
TI  - Antihistamine syrups and alcohol.

PMID- 11841649
TI  - Junctional epidermolysis bullosa with pyloric stenosis.

PMID- 11841650
TI  - Scalp alopecia as a result of immobilization following a traffic accident.

PMID- 11841651
TI  - Two cases of juvenile pemphigus vulgaris: long-term follow-up.

PMID- 11841652
TI  - Pachyonychia congenita: a case report.

PMID- 11841653
TI  - Rectorrhagia and lichen sclerosus in childhood.

PMID- 11841654
TI  - A case of malignant histiocytosis associated with skin involvement mimicking
      kwashiorkor.

PMID- 11841658
TI  - Molecular and genetic aspects of plant responses to osmotic stress.
AB  - Drought, high salinity and freezing impose osmotic stress on plants. Plants
      respond to the stress in part by modulating gene expression, which eventually
      leads to the restoration of cellular homeostasis, detoxification of toxins and
      recovery of growth. The signal transduction pathways mediating these adaptations
      can be dissected by combining forward and reverse genetic approaches with
      molecular, biochemical and physiological studies. Arabidopsis is a useful genetic
      model system for this purpose and its relatives including the halophyte
      Thellungiella halophila, can serve as valuable complementary genetic model
      systems.

PMID- 11841659
TI  - Drought- and desiccation-induced modulation of gene expression in plants.
AB  - Desiccation is the extreme form of dehydration. Tolerance of desiccation is
      acquired by seeds and in resurrection plants, a small group of angiosperms.
      Desiccation tolerance is the result of a complex cascade of molecular events,
      which can be divided into signal perception, signal transduction, gene activation
      and biochemical alterations leading to acquisition of tolerance. Many of these
      molecular processes are also observed during the dehydration of non-tolerant
      plants. Here we try to give an overview of the gene expression programmes that
      are triggered by dehydration, with particular reference to protective molecules
      and the regulation of their expression. Potential transgenic approaches to
      manipulating stress tolerance are discussed.

PMID- 11841660
TI  - Abscisic acid regulation of gene expression during water-deficit stress in the
      era of the Arabidopsis genome.
AB  - Changes in gene expression may lead to cellular adaptation of water-deficit
      stress, yet all of the induced mRNAs may not play this role. Changes in gene
      expression must be signalled by transduction mechanisms that first sense a water
      deficit. This first step triggers changes in gene expression that function to
      synthesize additional signals such as abscisic acid (ABA). The enzymes involved
      in ABA biosynthesis have been cloned and their regulation during water-deficit
      stress is being characterized. Once ABA levels are increased, further signalling
      mechanisms are initiated to signal new gene expression patterns that are proposed
      to play a role in cellular adaptation to water-deficit stress. As the genome of
      Arabidopsis is now completed, much more information can be exploited to
      characterize these responses.

PMID- 11841661
TI  - The role of glycine betaine in the protection of plants from stress: clues from
      transgenic plants.
AB  - The acclimation of a plant to a constantly changing environment involves the
      accumulation of certain organic compounds of low molecular mass, known
      collectively as compatible solutes, in the cytoplasm. The evidence from numerous
      investigations of the physiology, genetics, biophysics and biochemistry of plants
      strongly suggests that glycine betaine (GB), an amphoteric quaternary amine,
      plays an important role as a compatible solute in plants under various types of
      environmental stress, such as high levels of salts and low temperature. Plant
      species vary in their capacity to synthesize GB and some plants, such as spinach
      and barley, accumulate relatively high levels of GB in their chloroplasts while
      others, such as Arabidopsis and tobacco, do not synthesize this compound. Genetic
      engineering has allowed the introduction into GB-deficient species of
      biosynthetic pathways to GB from both micro-organisms and higher plants; this
      approach has facilitated investigations of the importance of GB in stress
      protection. In this review, we summarize recent progress in the genetic
      manipulation of the synthesis of GB, with special emphasis on the relationship
      between the protective effects of GB in vivo and those documented in vitro.

PMID- 11841662
TI  - Plant aquaporins: multifunctional water and solute channels with expanding roles.
AB  - There is strong evidence that aquaporins are central components in plant water
      relations. Plant species possess more aquaporin genes than species from other
      kingdoms. According to sequence similarities, four major groups have been
      identified, which can be further divided into subgroups that may correspond to
      localization and transport selectivity. They may be involved in compatible solute
      distribution, gas-transfer (CO2, NH3) as well as in micronutrient uptake (boric
      acid). Recent advances in determining the structure of some aquaporins gives
      further details on the mechanism of selectivity. Gating behaviour of aquaporins
      is poorly understood but evidence is mounting that phosphorylation, pH, pCa and
      osmotic gradients can affect water channel activity. Aquaporins are enriched in
      zones of fast cell division and expansion, or in areas where water flow or solute
      flux density would be expected to be high. This includes biotrophic interfaces
      between plants and parasites, between plants and symbiotic bacteria or fungi, and
      between germinating pollen and stigma. On a cellular level aquaporin clusters
      have been identified in some membranes. There is also a possibility that
      aquaporins in the endoplasmic reticulum may function in symplasmic transport if
      water can flow from cell to cell via the desmotubules in plasmodesmata.
      Functional characterization of aquaporins in the native membrane has raised doubt
      about the conclusiveness of expression patterns alone and need to be conducted in
      parallel. The challenge will be to elucidate gating on a molecular level and
      cellular level and to tie those findings into plant water relations on a
      macroscopic scale where various flow pathways need to be considered.

PMID- 11841663
TI  - ABA-based chemical signalling: the co-ordination of responses to stress in
      plants.
AB  - There is now strong evidence that the plant hormone abscisic acid (ABA) plays an
      important role in the regulation of stomatal behaviour and gas exchange of
      droughted plants. This regulation involves both long-distance transport and
      modulation of ABA concentration at the guard cells, as well as differential
      responses of the guard cells to a given dose of the hormone. We will describe how
      a plant can use the ABA signalling mechanism and other chemical signals to adjust
      the amount of water that it loses through its stomata in response to changes in
      both the rhizospheric and the aerial environment. The following components of the
      signalling process can play an important part in regulation: (a) ABA
      sequestration in the root; (b) ABA synthesis versus catabolism in the root; (c)
      the efficiency of ABA transfer across the root and into the xylem; (d) the
      exchange of ABA between the xylem lumen and the xylem parenchyma in the shoot;
      (e) the amount of ABA in the leaf symplastic reservoir and the efficiency of ABA
      sequestration and release from this compartment as regulated by factors such as
      root and leaf-sourced changes in pH; (f) cleavage of ABA from ABA conjugates in
      the leaf apoplast; (g) transfer of ABA from the leaf into the phloem; (h) the
      sensitivity of the guard cells to the [ABA] that finally reaches them; and lastly
      (i) the possible interaction between nitrate stress and the ABA signal.

PMID- 11841665
TI  - A possible stress physiological role of abscisic acid conjugates in root-to-shoot
      signalling.
AB  - Abscisic acid (ABA) conjugates, predominantly their glucose esters, have recently
      been shown to occur in the xylem sap of different plants. Under stress
      conditions, their concentration can rise substantially to levels that are higher
      than the concentration of free ABA. External ABA conjugates cannot penetrate
      apoplastic barriers in the root. They have to be hydrolysed by apoplastic enzymes
      in the root cortex. Liberated free ABA can then be redistributed to the root
      symplast and dragged directly across the endodermis to the stele. Endogenous ABA
      conjugates are formed in the cytosol of root cells, transported symplastically to
      the xylem parenchyma cells and released to the xylem vessels. The mechanism of
      release is unknown; it may include the action of ABC-transporters. Because of its
      extremely hydrophilic properties, ABA-GE is translocated in the xylem of the stem
      without any loss to the surrounding parenchyma. After arrival in the leaf
      apoplast, transporters for ABA-GE in the plasmalemma have to be postulated to
      redistribute the conjugates to the mesophyll cells. Additionally, apoplastic
      esterases can cleave the conjugate and release free ABA to the target cells and
      tissues. The activity of these esterases is increased when barley plants are
      subjected to salt stress.

PMID- 11841664
TI  - Interaction with ethylene: changing views on the role of abscisic acid in root
      and shoot growth responses to water stress.
AB  - Shoot and root growth are differentially sensitive to water stress. Interest in
      the involvement of hormones in regulating these responses has focused on abscisic
      acid (ABA) because it accumulates in shoot and root tissues under water-limited
      conditions, and because it usually inhibits growth when applied to well-watered
      plants. However, the effects of ABA can differ in stressed and non-stressed
      plants, and it is therefore advantageous to manipulate endogenous ABA levels
      under water-stressed conditions. Studies utilizing ABA-deficient mutants and
      inhibitors of ABA synthesis to decrease endogenous ABA levels, and experimental
      strategies to circumvent variation in plant water status with ABA deficiency, are
      changing the view of the role of ABA from the traditional idea that the hormone
      is generally involved in growth inhibition. In particular, studies of several
      species indicate that an important role of endogenous ABA is to limit ethylene
      production, and that as a result of this interaction ABA may often function to
      maintain rather than inhibit shoot and root growth. Despite early speculation
      that interaction between these hormones may influence many of the effects of
      water deficit, this topic has received little attention until recently.

PMID- 11841666
TI  - Signalling drought in guard cells.
AB  - A number of environmental conditions including drought, low humidity, cold and
      salinity subject plants to osmotic stress. A rapid plant response to such stress
      conditions is stomatal closure to reduce water loss from plants. From an external
      stress signal to stomatal closure, many molecular components constitute a signal
      transduction network that couples the stimulus to the response. Numerous studies
      have been directed to resolving the framework and molecular details of stress
      signalling pathways in plants. In guard cells, studies focus on the regulation of
      ion channels by abscisic acid (ABA), a chemical messenger for osmotic stress.
      Calcium, protein kinases and phosphatases, and membrane trafficking components
      have been shown to play a role in ABA signalling process in guard cells. Studies
      also implicate ABA-independent regulation of ion channels by osmotic stress. In
      particular, a direct osmosensing pathway for ion channel regulation in guard
      cells has been identified. These pathways form a complex signalling web that
      monitors water status in the environment and initiates responses in stomatal
      movements.

PMID- 11841667
TI  - Comparative physiology of salt and water stress.
AB  - Plant responses to salt and water stress have much in common. Salinity reduces
      the ability of plants to take up water, and this quickly causes reductions in
      growth rate, along with a suite of metabolic changes identical to those caused by
      water stress. The initial reduction in shoot growth is probably due to hormonal
      signals generated by the roots. There may be salt-specific effects that later
      have an impact on growth; if excessive amounts of salt enter the plant, salt will
      eventually rise to toxic levels in the older transpiring leaves, causing
      premature senescence, and reduce the photosynthetic leaf area of the plant to a
      level that cannot sustain growth. These effects take time to develop. Salt
      tolerant plants differ from salt-sensitive ones in having a low rate of Na+ and
      Cl-- transport to leaves, and the ability to compartmentalize these ions in
      vacuoles to prevent their build-up in cytoplasm or cell walls and thus avoid salt
      toxicity. In order to understand the processes that give rise to tolerance of
      salt, as distinct from tolerance of osmotic stress, and to identify genes that
      control the transport of salt across membranes, it is important to avoid
      treatments that induce cell plasmolysis, and to design experiments that
      distinguish between tolerance of salt and tolerance of water stress.

PMID- 11841668
TI  - Water deficits and hydraulic limits to leaf water supply.
AB  - Many aspects of plant water use -- particularly in response to soil drought --
      may have as their basis the alteration of hydraulic conductance from soil to
      canopy. The regulation of plant water potential (Psi) by stomatal control and
      leaf area adjustment may be necessary to maximize water uptake on the one hand,
      while avoiding loss of hydraulic contact with the soil water on the other.
      Modelling the changes in hydraulic conductance with pressure gradients in the
      continuum allows the prediction of water use as a function of soil environment
      and plant architectural and xylem traits. Large differences in water use between
      species can be attributed in part to differences in their 'hydraulic equipment'
      that is presumably optimized for drawing water from a particular temporal and
      spatial niche in the soil environment. A number of studies have identified
      hydraulic limits as the cause of partial or complete foliar dieback in response
      to drought. The interactions between root:shoot ratio, rooting depth, xylem
      properties, and soil properties in influencing the limits to canopy water supply
      can be used to predict which combinations should optimize water use in a given
      circumstance. The hydraulic approach can improve our understanding of the
      coupling of canopy processes to soil environment, and the adaptive significance
      of stomatal behaviour.

PMID- 11841669
TI  - Co-ordination of vapour and liquid phase water transport properties in plants.
AB  - The pathway for water movement from the soil through plants to the atmosphere can
      be represented by a series of liquid and vapour phase resistances. Stomatal
      regulation of vapour phase resistance balances transpiration with the efficiency
      of water supply to the leaves, avoiding leaf desiccation at one extreme, and
      unnecessary restriction of carbon dioxide uptake at the other. In addition to
      maintaining a long-term balance between vapour and liquid phase water transport
      resistances in plants, stomata are exquisitely sensitive to short-term, dynamic
      perturbations of liquid water transport. In balancing vapour and liquid phase
      water transport, stomata do not seem to distinguish among potential sources of
      variation in the apparent efficiency of delivery of water per guard cell complex.
      Therefore, an apparent soil-to-leaf hydraulic conductance based on relationships
      between liquid water fluxes and driving forces in situ seems to be the most
      versatile for interpretation of stomatal regulatory behaviour that achieves
      relative homeostasis of leaf water status in intact plants. Components of dynamic
      variation in apparent hydraulic conductance in intact plants include, exchange of
      water between the transpiration stream and internal storage compartments via
      capacitive discharge and recharge, cavitation and its reversal, temperature
      induced changes in the viscosity of water, direct effects of xylem sap
      composition on xylem hydraulic properties, and endogenous and environmentally
      induced variation in the activity of membrane water channels in the hydraulic
      pathway. Stomatal responses to humidity must also be considered in interpreting
      co-ordination of vapour and liquid phase water transport because homeostasis of
      bulk leaf water status can only be achieved through regulation of the actual
      transpirational flux. Results of studies conducted with multiple species point to
      considerable convergence with regard to co-ordination of stomatal and hydraulic
      properties. Because stomata apparently sense and respond to integrated and
      dynamic soil-to-leaf water transport properties, studies involving intact plants
      under both natural and controlled conditions are likely to yield the most useful
      new insights concerning stomatal co-ordination of transpiration with soil and
      plant hydraulic properties.

PMID- 11841670
TI  - Photosynthetic carbon assimilation and associated metabolism in relation to water
      deficits in higher plants.
AB  - Experimental studies on CO2 assimilation of mesophytic C3 plants in relation to
      relative water content (RWC) are discussed. Decreasing RWC slows the actual rate
      of photosynthetic CO2 assimilation (A) and decreases the potential rate (Apot).
      Generally, as RWC falls from c. 100 to c. 75%, the stomatal conductance (gs)
      decreases, and with it A. However, there are two general types of relation of
      Apot to RWC, which are called Type 1 and Type 2. Type 1 has two main phases. As
      RWC decreases from 100 to c. 75%, Apot is unaffected, but decreasing stomatal
      conductance (gs) results in smaller A, and lower CO2 concentration inside the
      leaf (Ci) and in the chloroplast (Cc), the latter falling possibly to the
      compensation point. Down-regulation of electron transport occurs by energy
      quenching mechanisms, and changes in carbohydrate and nitrogen metabolism are
      considered acclimatory, caused by low Ci and reversible by elevated CO2. Below
      75% RWC, there is metabolic inhibition of Apot, inhibition of A then being partly
      (but progressively less) reversible by elevated CO2; gs regulates A progressively
      less, and Ci and CO2 compensation point, Gamma rise. It is suggested that this is
      the true stress phase, where the decrease in Apot is caused by decreased ATP
      synthesis and a consequent decreased synthesis of RuBP. In the Type 2 response,
      Apot decreases progressively at RWC 100 to 75%, with A being progressively less
      restored to the unstressed value by elevated CO2. Decreased gs leads to a lower
      Ci and Cc but they probably do not reach compensation point: gs becomes
      progressively less important and metabolic limitations more important as RWC
      falls. The primary effect of low RWC on Apot is most probably caused by limited
      RuBP synthesis, as a result of decreased ATP synthesis, either through inhibition
      of Coupling Factor activity or amount due to increased ion concentration.
      Carbohydrate synthesis and accumulation decrease. Type 2 response is considered
      equivalent to Type 1 at RWC below c. 75%, with Apot inhibited by limited ATP and
      RuBP synthesis, respiratory metabolism dominates and Ci and Gamma rise. The
      importance of inhibited ATP synthesis as a primary cause of decreasing Apot is
      discussed. Factors determining the Type 1 and Type 2 responses are unknown.
      Electron transport is maintained (but down-regulated) in Types 1 and 2 over a
      wide range of RWC, and a large reduced/oxidized adenylate ratio results.
      Metabolic imbalance results in amino acid accumulation and decreased and altered
      protein synthesis. These conditions profoundly affect cell functions and
      ultimately cause cell death. Type 1 and 2 responses may reflect differences in gs
      and in sensitivity of metabolism to decreasing RWC.

PMID- 11841671
TI  - Induction of Crassulacean acid metabolism by water limitation.
AB  - Crassulacean acid metabolism (CAM), a key adaptation of photosynthetic carbon
      fixation to limited water availability, is characterized by nocturnal CO2
      fixation and daytime CO2 re-assimilation, which generally results in improved
      water-use efficiency. However, CAM plants display a remarkable degree of
      photosynthetic plasticity within a continuum of diel gas exchange patterns.
      Genotypic, ontogenetic and environmental factors combine to govern the extent to
      which CAM is expressed. The ecological diversity of CAM is mirrored by plasticity
      in a range of biochemical and physiological attributes. In C3/CAM-intermediate
      plants, limited water availability can induce or enhance the expression of CAM.
      CAM induction is controlled by a combination of transcriptional, post
      transcriptional and post-translational regulatory events. Early events in CAM
      induction point to a requirement for calcium and calcium-dependent protein kinase
      activities. Gene discovery efforts, improved transformation technologies and
      genetic models for CAM plants, coupled with detailed physiological
      investigations, will lead to new insights into the molecular genetic basis of
      induction processes and the circadian oscillator that governs carbon flux during
      CAM. Future integration of genomic, biochemical and physiological approaches in
      selected CAM models promise to provide a detailed view of the complex regulatory
      dynamics involved in CAM induction and modulation by water deficit. Such
      information is expected to have broad significance as the ecological and
      agricultural importance of CAM species increases in the face of global warming
      trends and the associated expansion of desertification in semi-arid regions
      around the world.

PMID- 11841672
TI  -  Soil conditions and plant growth'
AB  - Plants can respond to soil conditions in ways that can not readily be explained
      in terms of the ability of the roots to take up water and nutrients. Roots may
      sense difficult conditions in the soil and thence send inhibitory signals to the
      shoots which harden the plants against the consequences of a deteriorating or
      restrictive environment, especially if the plants' water supply is at risk.
      Generally, this behaviour can be interpreted as feedforward responses to the soil
      becoming too dry or too hard, or to the available soil volume being very small as
      with bonsai plants, or to roots' becoming infected with pathogens. However, soil
      that is too soft or in which the roots are forced to grow in very large pores can
      also induce large conservative responses, the significance of which is unclear.
      The inhibitory signals may affect stomatal conductance, cell expansion, cell
      division and the rate of leaf appearance. Their nature is still under debate, and
      the debate is becoming increasingly complex, which probably signifies that a
      network of hormonal and other responses is involved in attuning the growth and
      development of a plant to its environment.

PMID- 11841673
TI  - Plant water relations at elevated CO2 -- implications for water-limited
      environments.
AB  - Long-term exposure of plants to elevated [CO2] leads to a number of growth and
      physiological effects, many of which are interpreted in the context of
      ameliorating the negative impacts of drought. However, despite considerable
      study, a clear picture in terms of the influence of elevated [CO2] on plant water
      relations and the role that these effects play in determining the response of
      plants to elevated [CO2] under water-limited conditions has been slow to emerge.
      In this paper, four areas of research are examined that represent critical, yet
      uncertain, themes related to the response of plants to elevated [CO2] and
      drought. These include (1) fine-root proliferation and implications for whole
      plant water uptake; (2) enhanced water-use efficiency and consequences for
      drought tolerance; (3) reductions in stomatal conductance and impacts on leaf
      water potential; and (4) solute accumulation, osmotic adjustment and dehydration
      tolerance of leaves. A survey of the literature indicates that the growth of
      plants at elevated [CO2] can lead to conditions whereby plants maintain higher
      (less negative) leaf water potentials. The mechanisms that contribute to this
      effect are not fully known, although CO2-induced reductions in stomatal
      conductance, increases in whole-plant hydraulic conductance and osmotic
      adjustment may be important. Less understood are the interactive effects of
      elevated [CO2] and drought on fine-root production and water-use efficiency, and
      the contribution of these processes to plant growth in water-limited
      environments. Increases in water-use efficiency and reductions in water use can
      contribute to enhanced soil water content under elevated [CO2]. Herbaceous crops
      and grasslands are most responsive in this regard. The conservation of soil water
      at elevated [CO2] in other systems has been less studied, but in terms of
      maintaining growth or carbon gain during drought, the benefits of CO2-induced
      improvements in soil water content appear relatively minor. Nonetheless, because
      even small effects of elevated [CO2] on plant and soil water relations can have
      important implications for ecosystems, we conclude that this area of research
      deserves continued investigation. Future studies that focus on cellular
      mechanisms of plant response to elevated [CO2] and drought are needed, as are
      whole-plant investigations that emphasize the integration of processes throughout
      the soil--plant--atmosphere continuum. We suggest that the hydraulic principles
      that govern water transport provide an integrating framework that would allow CO2
      induced changes in stomatal conductance, leaf water potential, root growth and
      other processes to be uniquely evaluated within the context of whole-plant
      hydraulic conductance and water transport efficiency.

PMID- 11841674
TI  - Osmolyte accumulation: can it really help increase crop yield under drought
      conditions?
AB  - Osmolyte accumulation (OA) is frequently cited as a key putative mechanism for
      increasing yields of crops subjected to drought conditions. The hypothesis is
      that OA results in a number of benefits that sustain cell and tissue activity
      under water-deficit conditions. It has been proposed as an effective tolerance
      mechanism for water deficits, which could be enhanced in crops by traditional
      plant breeding, marker-assisted selection or genetic engineering, to generate
      drought-tolerant crops. However, field studies examining the association between
      OA and crop yield have tended to show no consistent benefit. The few, often
      cited, investigations with positive associations were obtained under severe water
      deficits with extremely low yields or conditions with special water-supply
      scenarios when much of the benefit is plant survival. Under conditions where
      water deficits threaten crop survival, yields are so low that even large
      fractional yield gains offer little practical benefit to growers. Indeed, the
      often-cited benefit of turgor maintenance in cells is likely to result in crop
      behaviour that is exactly opposite to what is beneficial to crops. The one clear
      mechanism identified in this review for beneficial yield responses to OA is in
      the maintenance of root development in order to reach water that may be available
      deeper in the soil profile.

PMID- 11841675
TI  - Editorial.

PMID- 11841677
TI  - Dropping out of maternal and child home visits.
AB  - The purpose of this study was to examine the relationship between nurse and
      client characteristics and the reason for client termination from public health
      nursing maternal and child home visits. The results indicate that clients who
      dropped out of services received more contacts from the nurses, missed more
      appointments with the nurses, and were given advice from the nurses on more
      topics. They also differed from clients who continued with services until the
      nursing care plan goals were met in reference to marital status, mental illness,
      source of payment for services, and use of WIC and food stamps. Nurses whose
      clients were more likely to continue until goals were met were higher in
      conscientiousness, learned more from experience, and learned less from coworkers
      or learning on their own. They also worked more hours per week. These findings
      have implications for practice and research.

PMID- 11841678
TI  - Outcome effectiveness of community health workers: an integrative literature
      review.
AB  - Community health workers (CHWs) are promoted as a mechanism to increase community
      involvement in health promotion efforts, despite little consensus about the role
      and its effectiveness. This article reviews the databased literature on CHW
      effectiveness, which indicates preliminary support for CHWs in increasing access
      to care, particularly in underserved populations. There are a smaller number of
      studies documenting outcomes in the areas of increased health knowledge, improved
      health status outcomes, and behavioral changes, with inconclusive results.
      Although CHWs show some promise as an intervention, the role can be doomed by
      overly high expectations, lack of a clear focus, and lack of documentation.
      Further research is required with an emphasis on stronger study design,
      documentation of CHW activities, and carefully defined target populations.

PMID- 11841679
TI  - Home visitation practice: models, documentation, and evaluation.
AB  - This article presents an evaluation of an in-home support program for at-risk
      mothers and their children. The program was multidisciplinary and was focused on
      development of parenting capacity and child-development competencies. The authors
      examine issues and problems that resulted from the blending of two models of
      practice-stabilization/crisis intervention and early intervention/health
      promotion-and describe the outcome-based evaluation that was used to assess
      initial and ongoing child development, parent-child interaction, family
      environment, and social support. When documentation and evaluation of practice
      and its effect on outcomes proved a considerable challenge, the authors developed
      a classification system to describe practice in three areas: situations
      addressed, interventions used, and referrals made. The article describes
      challenges surrounding program development, implementation, and evaluation.

PMID- 11841680
TI  - Smoking patterns among ninth-grade adolescents in the Pitkaranta district
      (Russia) and in eastern Finland.
AB  - This study describes how ninth-grade adolescents' smoking behavior in the
      Pitkaranta district (Russia) differs from their eastern Finland counterparts.
      Cross-sectional data from the second North Karelia Youth Study and the Pitkaranta
      Youth Study were used. Subjects were all (n=385) ninth-grade students in 10
      comprehensive schools in Pitkaranta and all (n=2098) students of the same age in
      24 comprehensive schools in eastern Finland. Students were asked about their
      smoking status, intentions to smoke, smoking situations, acquisition of tobacco
      products, and opportunity to smoke in the school area. The results showed very
      large differences in the smoking prevalence between Pitkaranta and eastern
      Finland. For boys, the prevalence of daily smoking was 29% and 19% in Pitkaranta
      and eastern Finland, respectively. The differences in girls were adverse: 7% and
      21% of girls in Pitkaranta and eastern Finland, respectively, were daily smokers.
      However, as many as one third of the nonsmoking girls in Pitkaranta stated that
      they may experiment or start smoking later. Boys in Pitkaranta had vaguer
      attitudes about remaining nonsmokers than boys in eastern Finland. This situation
      anticipates worsening of the smoking epidemic in Pitkaranta and requires an
      effective prevention policy and cooperation between different groups in society.

PMID- 11841681
TI  - A nursing model of community organization for change.
AB  - Community health nursing has the potential to reach beyond the individual and
      create interventions that affect the community as a whole. The Nursing Model of
      Community Organization for Change presented in this article describes the
      relationships among the concepts of empowerment, partnership, participation,
      cultural responsiveness, and community competence within a community organizing
      context. These concepts are implemented through the use of the Nursing Model of
      Community Organization for Change, which consists of four phases:
      assessment/reassessment, planning/design, implementation, and
      evaluation/dissemination. This nursing model provides a theoretical framework for
      community health professionals when creating community health interventions in
      partnership with community members.

PMID- 11841682
TI  - A participatory assessment of environmental health concerns in an Ojibwa
      community.
AB  - This research employed a participatory approach to explore environmental health
      (EH) concerns among Lac Courte Oreilles (LCO) Ojibwa Indians in Sawyer County,
      Wisconsin. The project was grounded in a broad ecological conceptualization of EH
      and in principles of health promotion and community participation. Community
      participation was accomplished through a steering committee that consisted of the
      primary author and LCO College faculty and community members. The selected
      assessment methodology was a self-administered survey mailed to LCO members in
      Sawyer County. Concern for environmental issues was high in this tribal
      community, especially for future generations. Concern was higher among older
      members and tribal members living on rather than off the reservation. Local
      environmental issues of concern were motorized water vehicles, effects from
      global warming, aging septic systems on waterways, unsafe driving, and
      contaminated lakes/streams. The LCO community can use survey results to inform
      further data needs and program development.

PMID- 11841683
TI  - Predictors of initiation of early sex in black and white adolescent females.
AB  - This study examined the extent to which problem solving, self-image, and other
      health-related factors predict age at first intercourse among Black and White
      adolescent females. The volunteer sample was 16 to 19 years old; 52% were Black
      (n=105), and 48% (n=97) were White. Adolescents were recruited from family
      planning clinics throughout South Carolina. Stratified analyses identified race
      as a modifier of the relationship between problem solving and time of first
      intercourse (early or delayed). Logistic regression revealed three predictors of
      early age at first intercourse in Black girls, but only one predictor in White
      girls. There were no race differentials in either age or the proportion of girls
      initiating early intercourse. However, Black girls who had less problem solving
      skill than their peers were five times more likely to have early intercourse,
      three times more likely to practice fewer health-promoting behaviors, and seven
      times more likely to have 10 or fewer years of education. Early intercourse was
      significantly associated with unprotected first intercourse. Our findings suggest
      that interventions may need to be tailored for different risk groups within Black
      populations of adolescent girls.

PMID- 11841684
TI  - Sexual risk taking among Taiwanese youth.
AB  - The purpose of this grounded theory study was to understand sexual risk-taking
      behavior among Taiwanese youth. Thirty-six participants were purposively selected
      for two to three semistructured, in-depth individual interviews. The constant
      comparative method and coding process were used for data analysis. The core
      category of preserving the fantasy of romantic innocence emerged from the initial
      data analysis to explain how and why young people engage in sexual risk taking.
      Accordingly, the subcategories of suppressing carnal knowledge and being swept
      away by love were developed. Suppressing carnal knowledge consisted of keeping
      silent, having an inadequate sexual education, and having stereotypical thinking
      and was identified as an explanation as to why young people cannot relate
      knowledge to actual practice. Being swept away by love included a false knowledge
      of one's sexual partner, shifting levels of intimacy, and nonacceptance of one's
      own sexuality. This conceptualization emphasizes the reasons why young people
      engage in sexual risk taking; that is, cultural reluctance to discuss sexuality
      openly. The implication of this theorizing is that interventions to reduce sexual
      risk taking should be done on an individual basis and should consider one's
      developmental context in order to increase one's skills in effectively discussing
      sex and sexuality.

PMID- 11841687
TI  - Hyaluronic acid and chondroitin sulphate A rapidly promote differentiation of
      immature DC with upregulation of costimulatory and antigen-presenting molecules,
      and enhancement of NF-kappaB and protein kinase activity.
AB  - Dendritic cells (DCs) have been identified as effective antigen-presenting cells
      (APCs). We demonstrate that extracellular matrix (ECM), hyaluronic acid (HA) and
      chondroitin sulphate A (CSA), in the presence of granulocyte-macrophage colony
      stimulating factor (GM-CSF), can rapidly promote the differentiation of monocyte
      derived immature DCs, as characterized by the remarkable upregulation of human
      leucocyte antigen (HLA-DR), CD40, CD54, CD80 and CD86 expression to levels higher
      than those in the DCs generated by culturing with GM-CSF and interleukin (IL)-4
      for 7 days and aggregation of the cells within 48 h. The upregulation of
      expression of HLA-DR, CD40, CD54, CD80 and CD86 was dose-dependent. Further
      studies showed that HA and CSA were able to augment nuclear factor (NF)-kappaB
      activity, as determined by gel mobility shift assay and promote protein
      phosphorylation. Inhibition of NF-kappaB by pyrolidine dithiocarbamate and sodium
      salicylate, and serine-threonine and tyrosine kinase by starosporine as well as
      phosphatidylinositide-3-kinase (PI-3-K) by wortmannin could prevent the effects
      of HA and CSA on the expression of HLA-DR, CD40, CD80 and CD86 in various
      degrees. Thus, our data demonstrate that HA or CSA can effectively and rapidly
      promote the differentiation of immature DC, suggesting that HA and CSA may
      possess a potential capacity in regulating immune responses.

PMID- 11841688
TI  - Non-lethal viral challenge of influenza haemagglutinin and nucleoprotein DNA
      vaccinated mice results in reduced viral replication.
AB  - Influenza DNA vaccines have been widely studied in experimental animal models and
      protection documented after lethal viral challenge. In this study, we have
      investigated the humoral response after a non-lethal viral challenge of mice
      vaccinated with plasmids encoding the influenza haemagglutinin (HA) or
      nucleoprotein (NP) genes. BALB/c mice were immunized intramuscularly with three
      doses (100 microg) of HA, NP or backbone plasmid at 3-week intervals, or
      alternatively infected intranasally, before being challenged with homologous
      virus 13 weeks later. Mice were then sacrificed at weekly intervals and the
      antibody-secreting cell response was examined systemically (spleen and bone
      marrow) and in the respiratory tract (nasal associated lymphoid tissue (NALT) and
      lungs). Sera were collected after each dose of vaccine and at sacrifice and
      analyzed by ELISA, haemagglutination inhibition and virus neutralization assays.
      We found that previous viral infection apparently elicits sterilizing immunity.
      Vaccination with HA or NP DNA significantly reduced viral replication in the
      nasal cavity after viral challenge, however, increases in serum antibody titres
      were observed after challenge. Prior to challenge, specific antibody-secreting
      cells were observed in the systemic compartment after HA or NP DNA vaccination
      but were also found in the NALT after viral challenge. In conclusion,
      intramuscular DNA vaccination resulted in immunological memory in the systemic
      compartment, which was rapidly reactivated upon viral challenge.

PMID- 11841690
TI  - The biological activity of serum IgE changes over the course of a primary
      response.
AB  - Mast-cell degranulation is triggered by the bridging of Fc receptor-bound antigen
      specific immunoglobulin IgE on the cell surface. In vitro experiments suggest
      that antibody affinity and nonspecific IgE may affect the mast-cell function,
      however, their importance in vivo is unclear. Investigations of the effects of
      these parameters on mast-cell sensitization were therefore carried out in a rat
      immunization model in which the IgE response is transient and peaks on days 10
      15. Between these two timepoints, significant changes in the level of specific
      IgE were not observed, but the avidity of specific IgE increased (P < 0.05).
      Total serum IgE peaked on day 10 and slowly declined, with the relative
      proportion of specific to total IgE increasing from day 10-15 (P < 0.05). Despite
      similar levels of antigen-specific IgE, increasing avidity and an increased
      proportion of specific IgE between days 10 and 15, the biological activity of IgE
      in the serum peaks on day 10 and declines rapidly, dropping around seven-fold by
      day 15 (P < 0.001). Mechanisms that could explain this finding, such as
      differential expression of IgE isoforms and changes in the fine specificity of
      the IgE response, are discussed.

PMID- 11841689
TI  - In vitro effect of bioactive compounds on influenza virus specific B- and T-cell
      responses.
AB  - In vitro studies have demonstrated positive effects of bioactive compounds on
      several functions of the immune system. In the present study, 25 of such
      compounds were tested for their immune modulating properties on influenza virus
      specific human B- and T-cell responses in vitro. One of these compounds, N-acetyl
      L-cysteine was shown to increase influenza virus specific lymphocyte
      proliferation and interferon(IFN)-gamma production at a concentration of 1.0
      mmol/l. Furthermore, N-acetyl-L-cysteine was found to enhance a specific activity
      of two influenza specific CD8+ cytotoxic T-lymphocyte clones directed towards HLA
      A*0201 and HLA-B*2705 restricted epitopes. A second compound, chlorogenic acid,
      was shown to enhance antigen specific proliferation of lymphocytes in three out
      of four donors, at concentrations of 10-50 micromol/l. Neither of the two
      compounds exhibited a positive effect on the production of influenza virus
      specific antibodies by human peripheral blood mononuclear cells in vitro.

PMID- 11841691
TI  - Modulation of IgD and CD20 by ligation of CD5 on tonsillar B cells.
AB  - The CD5 molecule, pan T cell marker, has been known to be expressed on a minor
      population of B cells, termed B-1 cells. However, the physiological function and
      pathological role of CD5+B (B-1) cells remain to be fully elucidated in humans.
      In the present study, we aimed to clarify the significance of CD5 expression on
      the B lymphocytes in human tonsil. Using flow cytometric analysis by three-colour
      immunofluorescence staining, we observed a majority of the cell surface CD5
      positive (sCD5+) B cells among the sIgD+ B-cell population, as previously
      described. Contrary to our expectation, approximately half of the sIgD+/sCD5+ B
      cells expressed CD38 on their cell surface. Furthermore, a small number of sCD5+
      were observed in the sIgD- B cell population. The addition of anti-CD5 monoclonal
      antibody (MoAb) to the culture induced downmodulation of sCD20 and sIgD of the
      tonsillar B cells, resulting in an increase of sCD38-/sIgD- (memory) B cells
      during the 10 day culture periods in the CD40/l cell culture system. Our findings
      suggest that ligation of CD5 might transduce the signal to regulate B cell
      maturation.

PMID- 11841692
TI  - Expression of CTLA-4 by human monocytes.
AB  - Cytotoxic T lymphocyte-associated molecule-4 (CTLA-4) is a receptor present on T
      cells that plays a critical role in the downregulation of antigen-activated
      immune responses. CTLA-4 interacts with the ligands CD80 and CD86 on antigen
      presenting cells (APC), and also directs the assembly of inhibitory signalling
      complexes that lead to quiescence or anergy. In this study, we show that human
      monocytes constitutively express CTLA-4. About 3% of monocytes expressed CTLA-4
      on the cell surface, whereas the intracellular expression was higher and present
      in about 20% of the monocytes. The sequences of the cDNAs from human monocytes
      were identical to the sequences of CTLA-4 from T cells. Expression of CTLA-4 was
      also confirmed in the activated myelomonocytic cell lines U937 and THP-1.
      Monocytes, but not T cells, activated by interferon (IFN)-gamma also secreted
      soluble CTLA-4 in vitro. The CTLA-4 expression was upregulated upon treatment
      with phorbol 12-myristate 13-acetate (PMA) and IFN-gamma. This increased
      expression could be partially abolished by staurosporine, an inhibitor of protein
      kinase C (PKC). Ligation of CTLA-4 in the monocyte-like cell-line U937 with
      antibodies against CTLA-4 partially inhibited the proliferation of cells and the
      upregulation of cell-surface markers CD86, CD54, HLA-DR and HLA-DQ induced by IFN
      gamma and Staphylococcus aureus, Cowan I strain (SAC). Ligation of CTLA-4
      suppressed the PMA-stimulated activation of transcription activator protein 1 (AP
      1) and nuclear factor (NF)-kappaB in the U937 cell line, indicating the
      involvement of an inhibitory signal transduction. These data provide the first
      evidence that CTLA-4 is constitutively expressed by monocytes and thus might be
      important for the regulation of immune mechanisms associated with monocytes.

PMID- 11841693
TI  - Human CD8+ CTL recognition and in vitro lysis of herpes simplex virus-infected
      cells by a non-MHC restricted mechanism.
AB  - Cytotoxic T lymphocytes (CTL) are important for the recognition and lysis of
      virally infected cells, but their effectiveness can be limited by viral immune
      evasion mechanisms. We investigated the immunophenotype and function of human
      CD8+ T cells raised in response to herpes simplex virus (HSV). The expanded
      population contained cells of an activated and mature phenotype, as determined by
      the expressions of CD25, CD45RO, CD57, CD95 and HLA-DR. Cultured cells also
      expressed CD45RA. These cells lysed autologous and allogeneic HSV-infected
      lymphoblastoid cell line (LCL) targets via a non-major histocompatibility complex
      (MHC) restricted recognition pathway. Inhibition assays showed the mechanism of
      cytotoxicity to be calcium-dependent, granule exocytosis pathway, rather than the
      internal disintegration pathway. Cold target competition assays indicated that a
      common CTL population contributed to the recognition of autologous and allogeneic
      infected targets. These effectors showed recognition of infected targets which
      was distinct from that of K562 cells. Non-MHC restricted lysis-associated
      molecule 2B4 (CD244) was upregulated on culturing and made a significant
      contribution to lysis of FcgammaR-bearing targets in a redirected killing assay.
      These findings suggest that CTL can recognize virally infected cells through a
      combination of non-MHC restricted mechanisms and may result in more efficient
      lysis than classical CD8+ T cells.

PMID- 11841694
TI  - Fc receptors are critical for autoimmune inflammatory damage to the central
      nervous system in experimental autoimmune encephalomyelitis.
AB  - Multiple sclerosis (MS) is simulated by various forms of experimental autoimmune
      encephalomyelitis, in which T cells, antibodies, cytokines and complementary
      factors interact with the central nervous system (CNS) myelin proteins and lead
      to inflammatory damage. We investigated the role of Fc receptors (FcRs), which
      link the cellular and humoral branches of the immune system, in myelin
      oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune
      encephalomyelitis (EAE), using two different FcRgamma knockout DBA/1 mice. The
      first knockout were the FcRgamma chain-deficient mice, which lack FcgammaRI,
      FcgammaRIII and Fc(epsilon)RI, while the second knockout mice lack only
      FcgammaRII. The lack of FcgammaRII enhanced the disease susceptibility with
      associated increased CNS demyelination. While FcRgamma+/+ DBA/1 mice also
      developed pronounced CNS infiltration and myelin destruction, FcRgamma-/-
      littermates were protected despite initial peripheral autoimmune responses to
      MOG. In vitro analyses revealed equivalent potentials of fluid phase phagocytosis
      of myelin and MOG in bone-marrow macrophages derived from both FcRgamma+/+ and
      FcRgamma-/- mice, while MOG-immunoglobulin (Ig)G immune complexes were only
      internalized by FcRgamma+/+ macrophages. This was associated with cellular
      activation in FcRgamma+/+ but not FcRgamma-/- macrophages, as assessed by the
      activation of intracellular mitogen activated protein (MAP)-kinase signalling
      elements. We propose that protection from EAE in FcRgamma-deficient mice is due
      to the inefficient antigen processing/presentation of myelin proteins during the
      induction of secondary immune responses locally in the CNS, which leads to
      demyelination. This demonstrates the importance of FcR in the promotion of
      autoimmune inflammation of the CNS and highlights the therapeutic possibility of
      treatment of MS with FcR-directed modalities.

PMID- 11841695
TI  - Generation of antibodies to the signal peptide of the MPT83 lipoprotein of
      Mycobacterium tuberculosis.
AB  - The mpt83 gene (Rv2873) encodes the exported MPT83 lipoprotein of Mycobacterium
      tuberculosis. The corresponding identical mpb83 gene of Mycobacterium bovis is
      expressed to varying extents in different substrains of M. bovis Bacille Calmette
      Guerin (BCG), BCG Tokyo and BCG Moreau being high producers and BCG Danish 1331,
      a low producer of the MPB83 protein. Immunization with the 13-mer N-terminal part
      of the signal peptide of MPT83, MINVQAKPAAAASC, coupled to keyhole limpet
      haemocyanin (KLH) through the added C-terminal cysteine resulted in rapid
      antibody formation monitored by enzyme-linked immunosorbent assay (ELISA) with
      free immunizing peptide on the solid phase. In ELISA, with four 20-mer
      overlapping peptides covering the N-terminal part of the MPT83 sequence, three
      polyclonal rabbit antisera reacted only with the N-terminal peptide. Antigenic
      signal peptide could not be detected in sonicates of BCG Tokyo and BCG Moreau.
      After SDS-PAGE and blotting, the antibodies reacted with sonicates of recombinant
      Escherichia coli containing the entire mpt83 gene including the signal sequence,
      but not with the 22 kDa form of native MPB83 purified from BCG culture filtrate.
      In partition chromatography the recMPT83 partitioned in the water phase while 26
      kDa MPB83 in BCG culture filtrate partitioned in the lipid phase confirming that
      lipidation at the N-terminal cysteine residue occurs after the splitting of the
      polypeptide chain by signal peptidase II.

PMID- 11841696
TI  - Megakaryothrombopoiesis during ex vivo expansion of human cord blood CD34+ cells
      using thrombopoietin.
AB  - Thrombopoietin (TPO) is one of the most promising stimulants for ex vivo
      expansion of haematopoietic stem cells. Previously, we have found that TPO
      induces a characteristic pattern of apoptosis during ex vivo expansion of human
      cord blood (CB) CD34+ cells and that the TPO-induced apoptotic cells belong to
      megakaryocyte (MK) lineage. In this study, we have examined the maturation of MK
      and platelet production in association with the TPO-induced apoptosis. CD34+
      cells, purified from human CB, were expanded in serum-free conditions stimulated
      with TPO. Apoptosis was confirmed by terminal deoxynucleotidyl transferase
      mediated deoxyuridine triphosphate-biotin nick end labelling (TUNEL) assay and
      electron microscopy (EM). Simultaneous measurement of DNA content and
      immunophenotyping revealed that the cells with higher DNA content (>8 N)
      constituted less than 5% of the CD41+ fractions until day 14, implying premature
      apoptosis of MKs before full polyploidization. Nevertheless, EM observation
      showed not only platelet territories but also newly produced platelets in which
      granules and microfilaments could be identified. Furthermore, flow cytometry
      demonstrated that the platelet fraction expressed P-selectin and an activation
      motif on GPIIb/IIIa recognized by monoclonal antibody PAC-1 upon stimulation with
      adenosine diphosphate (ADP). In addition, periodic acid-Schiff (PAS)-positive
      materials and nonspecific esterase activities could be demonstrated. Therefore,
      it is suggested that platelet production and the accompanying processes, rather
      than apoptosis only, be hastened during the ex vivo expansion of CB CD34+ cells
      when using TPO.

PMID- 11841697
TI  - NK1.1+ cells and T-cell activation in euthymic and thymectomized C57Bl/6 mice
      during acute Trypanosoma cruzi infection.
AB  - Natural killer (NK) cells may provide the basis for resistance to Trypanosoma
      cruzi infection, because the depletion of NK1.1 cells causes high levels of
      parasitemia in young C57Bl/6 mice infected with T. cruzi. Indeed, NK1.1 cells
      have been implicated in the early production of large amounts of interferon (IFN)
      gamma, an important cytokine in host resistance. The NK1.1 marker is also
      expressed on special subpopulations of T cells. Most NK1.1+ T cells are of thymic
      origin, and their constant generation may be prevented by thymectomy. This
      procedure, by itself, decreased parasitemia and increased resistance in young
      mice. However, the depletion of NK1.1+ cells by the chronic administration of a
      monoclonal antibody (MoAb) (PK-136) did not increase the parasitemia or mortality
      in thymectomized C57Bl/6 mice infected with T. cruzi (Tulahuen strain). To study
      the cross-talk between NK1.1+ cells and conventional T cells in this model, we
      examined the expression of activation/memory markers (CD45RB) on splenic CD4+ and
      CD8+ T cells from young euthymic or thymectomized mice with or without depletion
      of NK1.1+ cells and also in aged mice during acute infection. Resistance to
      infection correlated with the amount of CD4+ T cells that are already activated
      at the moment of infection, as judged by the number of splenic CD4+ T cells
      expressing CD45RB(-). In addition, the specific antibody response to T. cruzi
      antigens was precocious and an accumulation of immunoglobulin (Ig)M with little
      isotype switch occurred in euthymic mice depleted of NK1.1+ cells. The data
      presented here suggest that NK1.1+ cells have important regulatory functions in
      euthymic, but not in thymectomized mice infected with T. cruzi. These regulatory
      functions include a helper activity in the generation of effector or
      activated/memory T cells.

PMID- 11841699
TI  - Does Brussels listen? European health systems research in developing countries at
      the edge of extinction.

PMID- 11841698
TI  - Complement activation mediated by mannan-binding lectin in plasma from healthy
      individuals and from patients with SLE, Crohn's disease and colorectal cancer.
      Suppressed activation by SLE plasma.
AB  - We have developed a method for quantitating mannan-binding lectin (MBL)-induced
      activation of the complement system (MBL-C4-AC) in human plasma. This method and
      an assay for MBL concentration were applied to plasma samples from healthy
      individuals and patients with systemic lupus erythematosus (SLE), Crohn's disease
      (CD) and colorectal cancer (CRC). The MBL concentration was measured by an enzyme
      linked immunosorbent assay (ELISA) using monoclonal anti-MBL-antibodies and MBL
      C4-AC by an ELISA using solid-phase mannan, incubating with plasma samples and
      quantitating the complement (C) activation by the use of antibodies against the C
      split-products C4b/C4c. The MBL concentration was nonsignificantly elevated in
      plasma from SLE-patients, whereas MBL-C4-AC was suppressed (P < 0.04). There was
      no correlation between MBL concentration and MBL-C4-AC in plasma from SLE
      patients. In contrast, a significant correlation was found between the MBL
      concentration and MBL-C4-AC in plasma from healthy individuals. The C4
      concentration was significantly reduced (P < 0.002) in plasma from the SLE
      patients and showed a significant correlation to MBL-C4-AC. The MBL-C4-AC assay
      was highly effective in discriminating the SLE patients from the other patient
      groups and healthy individuals.

PMID- 11841700
TI  - Heavy schistosomiasis associated with poor short-term memory and slower reaction
      times in Tanzanian schoolchildren.
AB  - Cross-sectional studies of the relationship between helminth infection and
      cognitive function can be informative in ways that treatment studies cannot.
      However, interpretation of results of many previous studies has been complicated
      by the failure to control for many potentially confounding variables. We gave
      Tanzanian schoolchildren aged 9-14 a battery of 11 cognitive and three
      educational tests and assessed their level of helminth infection. We also took
      measurements of an extensive range of potentially confounding or mediating
      factors such as socioeconomic and educational factors, anthropometric and other
      biomedical measures. A total of 272 children were moderately or heavily infected
      with Schistosoma haematobium, hookworm or both helminth species and 117 were
      uninfected with either species. Multiple regression analyses, controlling for all
      confounding and mediating variables, revealed that children with a heavy S.
      haematobium infection had significantly lower scores than uninfected children on
      two tests of verbal short-term memory and two reaction time tasks. In one of
      these tests the effect was greatest for children with poor nutritional status.
      There was no association between infection and educational achievement, nor
      between moderate infection with either species of helminth and performance on the
      cognitive tests. We conclude that children with heavy worm burdens and poor
      nutritional status are most likely to suffer cognitive impairment, and the
      domains of verbal short-term memory and speed of information processing are those
      most likely to be affected.

PMID- 11841702
TI  - Evaluation of the World Health Organization standard tourniquet test and a
      modified tourniquet test in the diagnosis of dengue infection in Viet Nam.
AB  - OBJECTIVES: A positive tourniquet test is one of several clinical parameters
      considered by the World Health Organization to be important in the diagnosis of
      dengue haemorrhagic fever, but no formal evaluation of the test has been
      undertaken. As many doctors remain unconvinced of its usefulness, this study was
      designed to assess the diagnostic utility of both the standard test and a
      commonly employed modified test. METHODS: A prospective evaluation of the
      standard sphygmomanometer cuff tourniquet test, compared with a simple elastic
      cuff tourniquet test, was carried out in 1136 children with suspected dengue
      infection admitted to a provincial paediatric hospital in southern Viet Nam.
      RESULTS: There was good agreement between independent observers for both
      techniques, but the sphygmomanometer method resulted in consistently greater
      numbers of petechiae. This standard method had a sensitivity of 41.6% for dengue
      infection, with a specificity of 94.4%, positive predictive value of 98.3% and
      negative predictive value of 17.3%. The test differentiated poorly between dengue
      haemorrhagic fever (45% positive) and dengue fever (38% positive). The simple
      elastic tourniquet was less sensitive than the sphygmomanometer cuff, but at a
      threshold of 10 petechiae (compared with the WHO recommendation of 20) per 2.5
      cm2 the sensitivity for the elastic tourniquet rose to 45% (specificity 85%).
      Other evidence of bleeding was frequently present and the tourniquet test
      provided additional information to aid diagnosis in only 5% of cases. CONCLUSION:
      The conventional tourniquet test adds little to the diagnosis of dengue in
      hospitalized children. The simple, cheap elastic tourniquet may be useful in
      diagnosing dengue infection in busy rural health stations in dengue endemic areas
      of the tropics. A positive test should prompt close observation or early hospital
      referral, but a negative test does not exclude dengue infection.

PMID- 11841701
TI  - Pattern and associated factors of the neurolathyrism epidemic in Ethiopia.
AB  - OBJECTIVES: To describe the neurolathyrism epidemic in Ethiopia and to identify
      associated household factors. METHODS: We interviewed 589 randomly selected heads
      of household in Debre Sina district of Ethiopia, the area afflicted by the recent
      neurolathyrism epidemic. Disease information was obtained for 2987 family
      members. RESULTS: Neurolathyrism patients were detected in 56 (9.5%) households
      (prevalence rate 2.38%). The mean number of affected family members per household
      was 1.27 (SD 0.65, range 1-3). Most (77.5%) patients developed the disability
      during the epidemic (1995-1999). The median age at onset of paralysis was 11
      years with a range of 41 (range 3-44). Younger people were more affected during
      the epidemic than during the non-epidemic period (P=0.01). The presence of a
      neurolathyrism patient in the family was associated with illiteracy [adjusted OR
      (95% CI)=2.23 (1.07-5.10)] of the head of household, with owning a grass pea farm
      [adjusted OR (95% CI)=2.01 (1.04-3.88)] and with the exclusive cooking of grass
      pea foods using handmade traditional clay pots [adjusted OR (95% CI=2.06 (1.08
      3.90)]. CONCLUSION: Males aged 10-14 years were most affected by neurolathyrism.
      Increased household risk was associated with illiteracy of the head of the
      household and exclusive cooking of grass pea foods with handmade traditional clay
      pots.

PMID- 11841703
TI  - Taking a medical history and using a colour scale during clinical examination of
      pallor improves detection of anaemia.
AB  - We developed a colour tint scale to use as an aid in the clinical assessment of
      anaemia by measuring conjunctival pallor. The objectives of this study were to
      evaluate the accuracy and agreement among observers in detecting anaemia in three
      sequential phases with incremental information using clinical pallor of different
      anatomical sites, subsequently adding subjects' medical history for physical
      symptoms and the colour scale. After training in the application of these three
      sequential assessments, 12 primary health workers were assigned to independently
      examine 198 anaemic and 254 non-anaemic pregnant women while blind to the true
      anaemic status. Their assessments in each phase were then compared with the
      anaemic status based on haemoglobin level, measured using HemoCue, taken as the
      gold standard, to determine sensitivity and specificity, and agreements among
      observers in detecting anaemia were calculated. In the three sequential phases of
      assessment the sensitivities were 73.8, 78.3, 82.9% and specificities 76.0, 84.7
      and 90.9%, respectively. In each subsequent step, the improvements in both the
      sensitivity and specificity were statistically significant [P(chi2(McNemar)) <
      0.01]. Kappa statistics for agreement among 12 observers for assessing anaemia in
      the sequential phases were 0.50, 0.71 and 0.82, respectively. The Spearman rank
      correlation coefficient between haemoglobin level and the colour scale reading
      was 0.68 (P < 0.001). Taking medical history and incorporating a simple colour
      tint scale with examination of pallor improved the sensitivity, specificity and
      agreement for detection of anaemia by health workers.

PMID- 11841704
TI  - A systematic review of current knowledge of HIV epidemiology and of sexual
      behaviour in Nepal.
AB  - OBJECTIVE: To systematically review information on HIV epidemiology and on sexual
      behaviour in Nepal with a view to identifying gaps in current knowledge. METHODS:
      Systematic review covering electronic databases, web-based information, personal
      contact with experts and hand searching of key journals. RESULTS: HIV-1
      seroprevalence has been rising rapidly in association with high-risk behaviours,
      with current levels of 40% amongst the nation's injecting drug users and
      approaching 20% amongst Kathmandu's female commercial sex workers (FCSWs). HIV
      seroprevalence remains low in the general population (0.29% of 15-49 year olds).
      There are significant methodological limitations in many of the seroprevalence
      studies identified, and these estimates need to be treated with caution. There
      are extensive migration patterns both within the country and internationally
      which provide the potential for considerable sexual networking. However, studies
      of sexual behaviour have focused on FCSWs and the extent of sexual networks
      within the general population is largely unknown. CONCLUSIONS: Whilst some of the
      ingredients are present for an explosive HIV epidemic in Nepal, crucial knowledge
      on sexual behaviour in the general population is missing. Research on sexual
      networking is urgently required to guide HIV control in Nepal. There is also a
      need for further good-quality epidemiological studies of HIV seroprevalence.

PMID- 11841705
TI  - Socially marketed insecticide-treated nets improve malaria and anaemia in
      pregnancy in southern Tanzania.
AB  - OBJECTIVES: To study the uptake of socially marketed insecticide-treated nets
      (ITNs) and their impact on malaria and anaemia in pregnancy; and to report on a
      discount voucher system which aimed to increase coverage in pregnancy. METHODS: A
      12-month cross-sectional study of women in the second or third trimester of
      pregnancy. ITN use and other factors were assessed by questionnaire and a blood
      sample taken for malaria parasitaemia and anaemia. 'Non-users' of ITNs included
      both women not using any net and women using untreated nets. RESULTS: Fifty three
      per cent of pregnant women used ITNs. Women aged 15-19, primigravidae, unmarried
      women, and those with no access to cash had the lowest ITN use. Fewer ITN users
      were positive for malaria than ITN non-users (25 vs. 33%: P=0.06), and the
      protective efficacy (PE) for parasitaemia was 23% (CI 2-41). Multiparous ITN
      users had a twofold decrease in parasite density compared with multiparous non
      ITN users (625 parasites/microl vs. 1173 parasited/microl: P=0.01). Fewer ITN
      users were anaemic (Hb < 11 g/dl) than ITN non-users (72 vs. 82%: P=0.01). ITNs
      had a PE of 12% (CI 2-21) against mild anaemia and a PE of 38% (CI 4-60) against
      severe anaemia (Hb < 8 g/dl). There was a trend in the prevalence of severe, mild
      and no anaemia, and of high density, low density and no malaria infection by ITN
      status. Recently treated nets were most effective at preventing malaria and
      anaemia (prevalence of mild anaemia was 68% compared with 82% for those without
      nets (P=0.002); prevalence of malaria was 22% compared with 33% for those without
      nets (P=0.02). Knowledge and reported use of the discount voucher system were
      low. Further qualitative research is ongoing. CONCLUSIONS: A modest impact of
      ITNs on pregnancy malaria and anaemia was shown in our high malaria transmission
      setting. The development of ITN programmes for malaria control should include
      pregnant women as a specific target group.

PMID- 11841706
TI  - Female genital cutting in Kilimanjaro, Tanzania: changing attitudes?
AB  - OBJECTIVES: To study the prevalence, type, social correlates and attitudes
      towards female genital cutting (FGC) among urban women in Kilimanjaro, Tanzania;
      and to examine the association between FGC and gynaecological problems,
      reproductive tract infections (RTIs) and HIV. METHODS: In 1999, 379 women
      attending reproductive health care clinics were interviewed and underwent pelvic
      examination. Specimens for RTI/HIV diagnosis were taken. RESULTS: Seventeen per
      cent had undergone FGC, mostly clitoridectomy (97%). Female genital cutting
      prevalence was significantly lower among educated, Christian and Chagga women.
      Women aged >or=35 were twice as likely to be cut as those < 25 years. Seventy-six
      per cent of those who had undergone FGC intend not to perform the procedure on
      their daughters. Age < 25 years (P < 0.0001) and low parity (P < 0.01) were
      predictors of that intention. There was no association between RTIs, HIV or
      hepatitis B and FGC. CONCLUSION: FGC is still fairly common but there is evidence
      of a change of attitude towards the practice, especially among young women. The
      opportunity to educate women who attend reproductive health care facilities on
      FGC should be taken.

PMID- 11841707
TI  - Pathological differentiation of suspected cases of pentastomiasis in China.
AB  - We report nine cases of suspected pentastomiasis from China, and propose that
      diagnosis of this rare parasitic disease should be made aetio-pathologically,
      subaetio-pathologically, and presumptively. In none of our cases' lesions we
      could find either a whole or part of an embedded nymph; hence, no aetio
      pathologic diagnosis of pentastomid infection was established. In three cases,
      subaetio-pathologic diagnoses of pentastomiasis were made upon the discovery of a
      peculiar set of relics from lesions, namely two pairs of circumoral hooks of
      pentastomid from lesions. In one of these three cases, an extra scissors-like
      image indicating a longitudinal section of a hook of the embedded pentastomid
      nymph, probably Linguatula serrata, was found. In the other six cases, none of
      the relics of the aetiological agents were found, and our diagnoses were made
      presumptively by a series of relatively specific pathologic features, i.e. pearly
      lesions over the peritoneal surface of the abdominal cavity under the serosa of
      the intestinal wall or under the capsules of liver and spleen. They tend to be
      uniquely protuberant, sometimes linked by a short thin stalk to the surface. The
      hyalinization and calcification of these centrally caseated granulomatous nodules
      tend to be concentric and targetoid in appearance. Tuberculosis, the most easily
      confused condition, was easily ruled out pathohistologically. We believe that
      there is a need for presumptive pathologic diagnosis of human pentastomid
      infection not only in China, but worldwide.

PMID- 11841708
TI  - Adherence to treatment guidelines in primary health care facilities in Botswana.
AB  - OBJECTIVES: To assess the quality of nurses' prescribing through an assessment of
      their prescription in relation to diagnosis, and to investigate trends in drug
      use in Botswana primary health care. METHODS: Key data regarding nurses'
      adherence to national prescription and treatment guidelines were obtained through
      participatory observation using a questionnaire, related to each consultation.
      Adherence was categorized into (i) Full adherence, (ii) acceptable adherence,
      (iii) acceptable adherence, but one or more useless, but not dangerous, drugs and
      (iv) insufficient or dangerous treatment. The study comprises data on nurses'
      prescriptions, diagnoses and quality of dispensing in 2994 consecutive
      consultations in 30 primary health care facilities in three districts of
      Botswana: Ngami East, Gaborone and Kgalagadi North. RESULTS: The average number
      of drugs prescribed per patient was 2.3. Antibiotics were prescribed in 27% of
      all encounters. Full adherence was found in 44%, acceptable compliance in 20%,
      'acceptable, but one or more useless, but not dangerous, drugs' in 33% and
      'insufficient or dangerous treatment' in 3% of the consultations. Four factors
      were found to be independently associated with full adherence: patient age 16-31
      years, specified diagnosis, type of health facility and nurses' years of practice
      (4-11 years best). CONCLUSION: Although Botswana's health workers perform
      relatively well in terms of drug use indicators, there is a clear potential for
      improving health workers' adherence to national treatment guidelines.

PMID- 11841709
TI  - Examining out-of-pocket expenditure on health care in Nouna, Burkina Faso:
      implications for health policy.
AB  - OBJECTIVE: To examine household out-of-pocket expenditure on health care,
      particularly malaria treatment, in rural Burkina Faso. METHOD: Comprehensive
      analysis of out-of-pocket expenditure on health care through a descriptive
      analysis and a second, multivariate analysis using the Tobit model with emphasis
      on malaria, based on 800 urban and rural households in Nouna health district.
      RESULTS: Households will spend less on malaria, either in or outside the health
      facility, if given the choice to do so, because they feel confident to self-treat
      malaria. Seeking health care from a qualified health worker incurs more out-of
      pocket expenditure than self-treatment and traditional healers, and if necessary,
      households sell off assets to offset the expenditure. More than 80% of household
      out-of-pocket expenditure is allocated to drugs. CONCLUSION: This has policy
      implications for malaria control and the Roll Back Malaria Initiative.
      Communities need to be educated on the risks of malaria complications and the
      potential risk of inappropriate diagnosis and treatment. Drug or health services
      pricing policy needs to create an incentive to use the health services. In the
      fight against malaria, building alliances between households, traditional healers
      and health workers is essential.

PMID- 11841710
TI  - Nonvestibular schwannomas of the brain: a 7-year experience.
AB  - OBJECTIVE: Nonvestibular schwannomas are uncommon tumors of the brain. Trigeminal
      nerve schwannomas are the most common of this group, followed by
      glossopharyngeal, vagal, facial, accessory, hypoglossal, oculomotor, trochlear,
      and abducens nerve schwannomas, in descending order of frequency. We present a
      series of nonvestibular schwannomas that were surgically treated during a 7-year
      period. METHODS: Forty-six patients with schwannomas of Cranial Nerves V (26
      cases), VII (7 cases), IX, X, and XI (9 cases), XII (3 cases), and III (1 case)
      were microsurgically treated by the senior author (LNS) during a 7-year period,
      from 1993 to 2000. The clinical presentations, operative approaches,
      complications, and results were studied. RESULTS: Forty-five patients underwent
      gross total tumor resection in the first operation. One patient who had undergone
      subtotal tumor resection in the initial operation experienced a large recurrence
      after 4 years, and gross total tumor resection was achieved in the second
      operation. There were no postoperative deaths. Postoperative morbidity consisted
      of cerebrospinal fluid leaks for 5 patients (3 patients required a second
      operation to repair the leak, and 2 patients responded to lumbar drain
      placement), meningitis for 3 patients (2 cases were aseptic and 1 involved
      bacterial meningitis, which resolved with antibiotic therapy), vasospasm
      requiring angioplasty for 1 patient, temporary hemiparesis for 2 patients (who
      experienced good recoveries), and permanent hemiparesis for 1 patient. New
      cranial nerve deficits were observed for 24% of patients but were usually
      partial. The mean follow-up period was 33.3 months (range, 0.2-93 mo). No patient
      experienced tumor recurrence after complete tumor removal. The patient who
      experienced regrowth of the tumor did not exhibit recurrence after the second
      operation. The Karnofsky Performance Scale scores at the latest follow-up
      examination were 80 or more for 45 patients (98%) and 70 for 1 patient.
      CONCLUSION: Nonvestibular schwannomas can be treated via microsurgical excision,
      with excellent functional results. Recurrence is rare after total tumor excision,
      although much longer follow-up monitoring is required.

PMID- 11841711
TI  - Facial nerve neuromas: report of 10 cases and review of the literature.
AB  - OBJECTIVE: This study reviewed the management and outcomes of facial neuromas
      during the past decade at our institution. The goal was to analyze differences in
      presentation on the basis of location of the facial neuroma, review facial nerve
      function and hearing preservation postoperatively, and understand the
      characteristics of patients with tumors limited to the cerebellopontine angle or
      internal auditory canal. We also report an unusual case of a facial neuroma
      limited to the nervus intermedius. METHODS: Nine patients with facial neuromas
      and one with Jacobson's nerve neuroma underwent surgery, and total resection was
      accomplished in nine patients. A chart review for pre- and postoperative data was
      performed, after which all patients were evaluated on an outpatient basis.
      RESULTS: The mean age of the patients was 47 years; mean follow-up time was 33.1
      months. The most common presenting symptoms were hearing loss (six patients) and
      facial paresis (five patients). A total of five patients had progressive (four
      patients) or recurrent (one patient) facial paresis. No patient experienced
      worsened hearing as a result of surgery, and one experienced improvement in a
      conductive hearing deficit. Five patients required cable graft repair of the
      facial nerve; four improved to House-Brackmann Grade 3 facial paresis. Four of
      five patients with preserved anatomic continuity of the facial nerve regained
      normal facial function. There were no surgical complications. No tumors have
      recurred during follow-up. We report the second nerve sheath tumor limited to the
      nervus intermedius. CONCLUSION: This series documents that facial neuromas can be
      resected safely with preservation of facial nerve and hearing function.
      Preservation of anatomic continuity of the facial nerve should be attempted, and
      it does not seem to lead to frequent recurrence. Tumors limited to the
      cerebellopontine angle/internal auditory canal are a unique subset of facial
      neuromas with characteristics that vary greatly from facial neuromas in other
      locations, and they are indistinguishable clinically from acoustic neuromas.

PMID- 11841712
TI  - Early endovascular treatment of ruptured cerebral aneurysms in patients in very
      poor neurological condition.
AB  - OBJECTIVE: In patients in very poor neurological condition (World Federation of
      Neurosurgical Societies Grade V) with aneurysmal subarachnoid hemorrhage, early
      surgery to prevent rebleeding and to allow appropriate treatment of complications
      is often difficult. The aim of the present study was to evaluate whether early
      endovascular treatment followed by aggressive proactive treatment of
      complications (prophylactic hypervolemic hemodilution, hypertensive treatment in
      the event of systemic hypotension, and appropriate treatment of intracranial
      hypertension) is an acceptable management strategy for these patients. METHODS:
      We prospectively studied 11 consecutive patients who presented with acutely
      ruptured aneurysms and were in very poor neurological condition after
      resuscitation (World Federation of Neurosurgical Societies Grade V) but did not
      have a significant intracerebral hemorrhage. These patients received endovascular
      treatment with Guglielmi detachable coils (Boston Scientific/Target, Fremont,
      CA). Follow-up consisted of a clinical evaluation based on the Glasgow Outcome
      Scale. A control angiogram was obtained after 6 months in patients with favorable
      outcomes to evaluate the occlusion of the aneurysm. RESULTS: There were no deaths
      or complications directly related to the procedure. Two patients died as a
      consequence of increased intracranial pressure. The mean follow-up of the
      surviving patients was 12 months. Two patients had early rebleeding after the
      coiling and required further treatment. Four patients had good outcomes, two
      patients were moderately disabled, and three patients were severely disabled.
      CONCLUSION: This study demonstrates that early endovascular treatment of acutely
      ruptured cerebral aneurysms in patients evaluated as World Federation of
      Neurosurgical Societies Grade V allows for aggressive treatment of intracranial
      hypertension and vasospasm. More than half of the patients had favorable
      outcomes. Therefore, early endovascular treatment seems to be a valuable
      alternative to early surgery in patients who present with a very poor clinical
      grade after subarachnoid hemorrhage. The results of this study are promising but
      must be interpreted with caution, because a small number of patients were
      studied.

PMID- 11841714
TI  - Detection of the residual lumen of intracranial aneurysms immediately after coil
      embolization by three-dimensional digital subtraction angiographic virtual
      endoscopic imaging.
AB  - OBJECTIVE: Detection of a small residual lumen after coil embolization is often
      difficult because of the coil mass and the overlap of the cerebral arteries. The
      purpose of this study was to assess the usefulness of virtual endoscopic (VE)
      analysis of three-dimensional digital subtraction angiographic (DSA) images for
      evaluation of aneurysmal occlusion immediately after the procedure. METHODS:
      Twenty-seven intracranial aneurysms were treated with coil embolization using a
      three-dimensional DSA system. Biplane and rotational DSA scanning was performed
      before and immediately after the procedures. VE images were obtained at a
      separate workstation, after transfer of the rotational images. Two-dimensional
      (2D) DSA images and VE images obtained after the procedure were assessed with
      respect to aneurysmal occlusion. Morphological outcomes and other factors,
      including location, size, volumetric ratio (coil volume/aneurysm volume), and
      residual sites, were also evaluated. RESULTS: Seven aneurysms were evaluated as
      complete occlusion (CO) on both 2D DSA images and VE images. Twelve aneurysms
      exhibited residual lumina on both 2D DSA images and VE images. Five aneurysms
      were evaluated as CO on 2D DSA images and as incomplete occlusion on VE images.
      There were no recurrences among the aneurysms that were evaluated as CO on VE
      images. Two of five aneurysms that were evaluated as CO on 2D DSA images and as
      incomplete occlusion on VE images demonstrated regrowth in follow-up
      examinations. Residual sites and volumetric ratios were correlated with
      aneurysmal regrowth. CONCLUSION: VE imaging can demonstrate a residual lumen more
      frequently than can 2D DSA imaging and is useful for evaluating aneurysmal
      occlusion after coil embolization.

PMID- 11841713
TI  - Carotid angioplasty and stent placement: a prospective analysis of perioperative
      complications and impact of intravenously administered abciximab.
AB  - OBJECTIVE: To determine the frequency of perioperative complications since the
      introduction of abciximab, we prospectively evaluated our experience in a
      consecutive series of patients undergoing carotid angioplasty and stent placement
      (CAS). CAS has been introduced recently for treatment of carotid artery stenosis.
      A major limitation to this modality is the risk of perioperative thromboembolic
      and ischemic events. To reduce the risk of ischemic complications, abciximab, a
      platelet glycoprotein IIb/IIIa receptor inhibitor, has been introduced as
      adjunctive treatment for high-risk patients. METHODS: Each patient was evaluated
      by a neurologist before, immediately after, and 24 hours after CAS for
      identification and classification of new neurological deficits. Bleeding events
      or other complications during hospitalization were recorded. Bleeding
      complications were classified as major (hemoglobin decrease,g5 g/dl), minor
      (hemoglobin decrease, 3-5 g/dl), or insignificant. Abciximab was administered
      intravenously as a single bolus (0.25 mg/kg) and then via infusion (10
      microg/min) for 12 hours as an adjunct to CAS in patients considered to be at
      high risk for thromboembolic events owing to recent ischemic symptoms and/or
      complex lesion morphology. RESULTS: Intravenously administered abciximab was used
      in 37 patients (mean age, 70 yr; 21 patients were men) as an adjunct to high-risk
      CAS. Thirty-three other patients underwent CAS performed with standard
      intraprocedural heparinization (mean age, 69 yr; 17 patients were men). Minor
      ischemic strokes were observed in 1 of 37 abciximab-treated patients and in 4 of
      33 heparin-treated patients. No major ischemic strokes were observed in either
      group. Transient neurological deficits were observed in nine patients in the
      abciximab-treated group and in one patient in the heparin-treated group.
      Transient neurological deficits in abciximab-treated patients were mainly related
      to hemodynamic factors (associated with balloon inflation in two patients and
      with hypotension in another two patients) or occurred after completion of
      infusion (in three patients). Minor bleeding complications were observed in three
      patients who received abciximab and in four patients who received standard
      heparinization. Major bleeding complications were observed in four patients from
      each group. Two patients who received abciximab developed intracerebral
      hemorrhages; one hemorrhage was fatal. CONCLUSION: The frequency of ischemic
      stroke in high-risk patients (3%) with the use of intravenously administered
      abciximab was lower, but not significantly so, than rates observed in lower-risk
      patients (12%), although the benefit was lost because of the high rate of
      intracranial hemorrhages (5%). Further efforts are required to determine
      appropriate selection criteria for use of intravenously administered abciximab
      and the effect of other strategies that involve distal protection devices.

PMID- 11841715
TI  - Reoperation for acute hemispheric stroke after carotid endarterectomy: is there
      any value?
AB  - OBJECTIVE: Because the clinical benefit of urgent investigation and carotid re
      repair for acute stroke complicating carotid endarterectomy (CEA) is uncertain,
      the results of this approach were examined in a large series of patients.
      METHODS: In a consecutive series of 700 CEAs, 24 patients (3.4%) had a
      postoperative stroke. Thirteen of these 24 patients experienced major hemispheric
      deficits (hemiplegia with or without aphasia, forced eye deviation, and decreased
      consciousness) that prompted either immediate surgical reexploration or cerebral
      angiography with reoperation on the basis of angiogram results; these 13 patients
      are the subject of this report. Neurological improvement was attributed to
      carotid reopening when affected muscle strength increased to antigravity power
      within 6 hours of reoperation. RESULTS: Of the 13 patients with severe
      postoperative deficits, 5 (38%) had the deficits when they awakened, 7 deficits
      occurred within 12 hours of surgery, and the only intracerebral hemorrhage in
      this series occurred 8 days after surgery. Five patients underwent urgent
      reoperation without angiography, and carotid occlusions were found and repaired
      in two patients. In another patient, the carotid was patent, and an intra
      arterial injection of tissue plasminogen activator (20 mg) was given. In the
      seven patients who underwent cerebral angiography as the first step, two carotid
      occlusions and one residual stenosis with thrombus were found and repaired on an
      urgent basis. Surgical reopening of occluded arteries was followed by improvement
      in two of four patients, and early improvement was noted in one patient with a
      stenosis correction as well as in the patient who received intraoperative tissue
      plasminogen activator. Four patients who underwent urgent reoperation did not
      demonstrate a benefit soon after surgery. Two patients died, two were left with
      major deficits and five with moderate deficits, and four patients eventually had
      good recovery at a minimum of 6 months of follow-up. CONCLUSION: In this series,
      approximately one-half of hemispheric strokes complicating CEA had an underlying
      correctable lesion (occlusion or stenosis), and these patients typically had
      delayed-onset strokes. Approximately one-half of these patients improved early as
      a result of reopening, although computed tomography revealed new infarcts in most
      of them. Urgent carotid repair may benefit a minority of selected patients who
      have a major stroke after CEA.

PMID- 11841716
TI  - Repeat radiosurgery for refractory trigeminal neuralgia.
AB  - OBJECTIVE: Stereotactic radiosurgery has become an important and minimally
      invasive alternative for patients with refractory trigeminal neuralgia. When a
      second procedure is necessary, the outcomes are unknown. The degree of pain
      relief and morbidity after repeat radiosurgery were studied. METHODS: Thirty-one
      patients underwent a second gamma knife radiosurgery procedure because of
      unsatisfactory or unsustained relief of pain after the first procedure. Twenty
      seven patients were assessable at median follow-up periods of 42.7 and 20.4
      months after the first and second procedures, respectively. Most patients had
      undergone multiple previous operations of other types (microvascular
      decompression, radiofrequency rhizotomy, glycerol rhizotomy, balloon
      compression). The median target doses of the first and second radiosurgeries were
      75 and 64 Gy, respectively. All patients were evaluated by a physician who did
      not participate in patient treatment. RESULTS: After the first radiosurgical
      procedure, 13 patients had an excellent response initially (complete relief
      without any medication), 3 had a good response (complete relief with some
      medication), 7 had a fair response (>50% relief), and 4 had a poor response (<50%
      pain relief or treatment failure). Repeat radiosurgery was performed in patients
      with recurrent or residual pain. After the second radiosurgical procedure, 5
      patients had an excellent response, 8 had a good response, 10 had a fair
      response, and 4 had a poor response. Thirteen patients (48%) achieved complete
      pain relief (with or without medication). Two patients (7.4%) experienced new
      sensory symptoms after the first radiosurgical procedure, and three (12.7%,
      actuarial) experienced new sensory symptoms after the second procedure.
      CONCLUSION: Repeat radiosurgery provided a similar rate of pain relief as the
      first procedure, despite a modest dose reduction. The risk of new sensory
      symptoms was increased, but no other morbidity was identified. For patients who
      experience recurrent pain and choose to undergo a second procedure, our current
      procedure is to deliver a maximum dose of 50 to 60 Gy to a trigeminal target
      anterior to the root entry zone near the entrance of the nerve beneath the
      petrous dura.

PMID- 11841717
TI  - Pure subdural hematomas: a postmortem analysis of their form and bleeding points.
AB  - OBJECTIVE: Although the literature concerning subdural hematomas (SDHs) is vast,
      few data are available as to the sources and related clinical differences of
      SDHs. Pure SDHs of arterial versus venous origin should be compared in terms of
      cause, size, space-occupying effect, and form. METHODS: We analyzed data from 46
      patients who died as a result of pure SDHs. Twenty-three SDHs resulted from
      bridging vein ruptures and 23 from torn cortical arteries. We performed a
      morphometric analysis of the intracranial situation on the horizontal plane at
      the level of the greatest fronto-occipital diameter. We included in our analysis
      the clinical one-dimensional parameters (e.g., hematoma thickness, midline
      shift); the areas of the hemispheres, the SDHs, and their displacement; and the
      hematoma volume. RESULTS: Most of the investigated postmortem characteristics of
      both types of hematomas were similar, with the exception of the form and the
      midline shift. SDHs resulting from arterial ruptures (which are generally located
      in the temporoparietal region) differ in form from those caused by bridging vein
      ruptures (which typically rupture in the frontoparietal parasagittal region).
      CONCLUSION: The form difference allows the probable rupture site to be estimated;
      this observation might prove useful for clinical purposes.

PMID- 11841718
TI  - Persistent iliac crest donor site pain: independent outcome assessment.
AB  - OBJECTIVE: This study objectively defines the incidence of donor site pain in an
      independent outcome analysis. In addition, this study identifies the significant
      discrepancies that are observed when independent outcome assessment results are
      compared with the incidences determined by review of the operating surgeon's
      documented findings. METHODS: A review of patients who underwent iliac bone graft
      harvesting by a single neurosurgeon was conducted. The presence of iliac crest
      donor site pain, at a time remote from surgery, as determined by specific
      questioning and recorded in the neurosurgeon's written evaluation was compared
      with independent assessment findings obtained in structured telephone
      questionnaire interviews. During a 4-year period, 105 patients met the inclusion
      criteria. Both the operating surgeon' and independent interviewer's follow-up
      evaluations were completed for all study patients. Pain was classified into three
      categories, i.e., no pain, acceptable pain, or unacceptable pain. Patients were
      also asked to assess the severity of their donor site pain by using a visual
      analog scale. Statistical analyses comparing the incidences of iliac crest donor
      site pain in the operating surgeon's evaluations and the independent assessments
      were performed. RESULTS: When evaluated at a time remote from surgery, the true
      incidence of iliac crest donor site pain after graft harvest procedures (34%) was
      significantly greater than previously appreciated by the neurosurgeon (8%).
      Although occasional or mild pain was observed for 31% of patients, only 3% of all
      patients experienced unacceptable pain. CONCLUSION: Independent outcome
      assessment values should be provided to patients in preoperative discussions
      regarding donor site morbidity. Objective outcome analysis, based on independent
      observations, is crucial for the most accurate interpretation of perceptions of
      iliac crest donor site pain.

PMID- 11841719
TI  - Efficacy of the morphine-Adcon-L compound in the management of postoperative pain
      after lumbar microdiscectomy.
AB  - OBJECTIVE: Epidural analgesia is a pharmacological technique for operative and
      postoperative pain control. It has been used with lumbar microdiscectomy to
      facilitate management of surgical pain, shorten patient recovery time, and
      increase patient satisfaction with the procedure and the hospital stay. Adcon-L
      (Gliatech, Inc., Cleveland, OH) (adhesion control in a barrier gel) has been
      demonstrated to act as a barrier to the development of epidural fibrosis after
      lumbar procedures, minimizing the formation of fibrotic scar and improving the
      long-term outcome. In this study, we used Adcon-L as a vehicle to administer 1 mg
      of morphine epidurally to patients who underwent lumbar microdiscectomy. Our
      objective was to evaluate the safety and analgesic efficacy of this compound.
      METHODS: A randomized, controlled, double-blind study was conducted in 100
      patients. Patients were randomized to two groups: the morphine-Adcon-L (M-ADL)
      group (n = 51 patients) or the Adcon-L control group (n = 49 patients). Outcome
      measures included: 1) a visual analog scale to assess the intensity of
      spontaneous low back and radicular pain, 2) a straight leg-raising maneuver to
      assess the degree of leg elevation in relation to evoked sciatic pain, 3)
      postoperative time to comfortable walking, 4) duration of postoperative
      hospitalization, 5) required amount of postoperative analgesics, and 6)
      postoperative work time loss. RESULTS: No intraoperative or postoperative
      complications were observed. No clinically relevant adverse events, such as
      urinary retention, respiratory disturbances, or wound infections were reported in
      the M-ADL group. At the time of hospital discharge, results were as follows: 1)
      the M-ADL group had significantly lower pain intensity scores (mean value of
      postoperative visual analog scale, 12.3 mm +/- 0.9 in the M-ADL group versus 24.7
      mm +/- 11.5 in the control group[P < 0.0001]); 2) the M-ADL group consumed
      significantly less analgesics: 57.4% of M-ADL patients versus 95.9% of controls
      received analgesics in the hospital, and 23.5% of M-ADL patients versus 55.1% of
      controls used analgesics at home (P < 0.0001); 3) the M-ADL group had
      significantly shorter hospital stays (1.37 +/- 0.07 d versus 2.53 +/- 0.12 d in
      the control group[P < 0.0001]); 4) the M-ADL group had a significantly higher
      degree of symptomatic leg elevation in the straight leg raising (mean
      postoperative straight leg-raising test, 64.41 degrees +/- 1.59 versus 57.77
      degrees +/- 1.85 in the controls[P = 0.02]); and 5) the M-ADL group lost
      significantly less postoperative work time (21.67 +/- 0.92 d versus 29.47 +/-
      1.18 d in the control group). In addition, at 1 year of follow-up, there was no
      clinical evidence of late-onset neurological complications. CONCLUSION: The
      epidural application of the compound M-ADL after lumbar microdiscectomy was found
      to be safe and effective, and it significantly improved postoperative pain
      control and return to function.

PMID- 11841720
TI  - Cerebral autoregulation among patients with symptoms of hydrocephalus.
AB  - OBJECTIVE: To study the relationship between the resistance to cerebrospinal
      fluid (CSF) outflow and cerebral autoregulation. METHODS: We examined 35 patients
      who presented with ventricular dilation and clinical symptoms of communicating
      hydrocephalus. For all of these patients, CSF compensatory reserve was
      investigated by using a computerized infusion test, with simultaneous recording
      of blood flow velocity wave forms (by using transcranial Doppler ultrasonography)
      and arterial blood pressure (with a Finapress finger cuff). The resistance to CSF
      outflow was calculated as the absolute increase in intracranial pressure
      (interpolated over vasogenic waves) divided by the infusion rate (1.5 ml/min in
      most cases). The index of autoregulation was assessed as a correlation
      coefficient (moving time window of 5 min) between slow waves (with periods of 20
      s to 2 min) in mean blood flow velocity and cerebral perfusion pressure. RESULTS:
      The mean intracranial pressure increased during the test, from 6 mm Hg (standard
      deviation, 6 mm Hg) to 20 mm Hg (standard deviation, 10 mm Hg) (P < 0.0001). The
      index of autoregulation was significantly correlated with the resistance to CSF
      outflow (r = -0.41, P < 0.03), indicating better autoregulation with greater
      resistance to CSF outflow. CONCLUSION: Patients presenting with ventricular
      dilation may exhibit either decreased (atrophy) or increased (normal-pressure
      hydrocephalus) resistance to CSF outflow. Increased resistance is correlated with
      preserved autoregulation. Patients with low resistance, suggesting brain atrophy,
      more often have disturbed autoregulation in the middle cerebral artery territory,
      as assessed by transcranial Doppler ultrasonography.

PMID- 11841721
TI  - Measurement of cerebrospinal fluid flow at the cerebral aqueduct by use of phase
      contrast magnetic resonance imaging: technique validation and utility in
      diagnosing idiopathic normal pressure hydrocephalus.
AB  - OBJECTIVE: We analyzed the reliability of a protocol for measuring quantitative
      cerebrospinal fluid (CSF) flow at the cerebral aqueduct and established the range
      of CSF flows in normal elderly patients, patients with Alzheimer's and other
      forms of dementia, and patients with idiopathic normal pressure hydrocephalus
      (NPH). METHODS: A constant flow phantom was used to establish the accuracy of the
      CSF flow measurement. The clinical variability of the measurement was estimated
      by calculating the standard deviations and coefficients of variation of intra-
      and interobserver and intertrial data sets derived from three normal volunteers.
      A total of 236 patients were studied, including 47 normal elderly patients, 115
      patients with cognitive impairment (9 with mild cognitive impairment, 46 with
      Alzheimer's disease, and 60 with other cognitive impairment), 31 patients in whom
      NPH was suspected but ultimately excluded, and 43 patients with a final clinical
      diagnosis of NPH. RESULTS: The intraobserver, interobserver, and intertrial
      measurement variations of 6.4, 5.4, and 8.8%, respectively, were substantially
      smaller than the wide variation observed among subjects. There was no
      statistically significant difference in flow between normal elderly patients and
      patients with cognitive impairment (P = 0.91). When these populations were
      pooled, the average flow was 8.47 ml/min (standard deviation, 4.23; range, 0.9
      18.5 ml/min). The average flow rate in patients with a final clinical diagnosis
      of NPH was 27.4 ml/min (standard deviation, 15.3; range, 3.13-62.2 ml/min). This
      was significantly higher than the flow rate in each of the other three groups
      (all, P < 0.001). CONCLUSION: CSF flow measurements of less than 18 ml/min with a
      sinusoidal flow pattern are normal. CSF flow of greater than 18 ml/min suggests
      idiopathic NPH.

PMID- 11841722
TI  - Levels of soluble adhesion molecules are elevated in the cerebrospinal fluid of
      children with moyamoya syndrome.
AB  - OBJECTIVE: The pathogenesis of moyamoya syndrome is unknown; however, previous
      studies suggested an inflammatory component. Because adhesion molecules mediate
      inflammation during cerebral ischemia, we measured the levels of soluble isoforms
      of the endothelial adhesion molecules vascular cell adhesion molecule Type 1,
      intercellular adhesion molecule Type 1, and E-selectin in serum and cerebrospinal
      fluid (CSF) samples from children with moyamoya syndrome. METHODS: Serum and CSF
      samples were obtained from children with moyamoya syndrome (n = 20) and patients
      with congenital spinal deformities (n = 20). Soluble vascular cell adhesion
      molecule Type 1, intercellular adhesion molecule Type 1, and E-selectin levels
      were measured in enzyme-linked immunoassays. The correlation between the levels
      of soluble adhesion molecules and the Suzuki angiographic classification was
      analyzed. CSF/serum albumin index values were also measured, to determine the
      integrity of the blood-brain barrier. RESULTS: Compared with the control group,
      children with moyamoya syndrome exhibited significantly elevated CSF levels of
      soluble vascular cell adhesion molecule Type 1, intercellular adhesion molecule
      Type 1, and E-selectin. The albumin index for the moyamoya group was 9, which was
      significantly higher than that for the control group. However, there were no
      differences in the serum levels of the three soluble adhesion molecules and no
      correlations between age, Suzuki classification, and serum and CSF levels of
      adhesion molecules. CONCLUSION: Our study demonstrates increased CSF levels of
      soluble endothelial adhesion molecules, suggesting that children with moyamoya
      syndrome have ongoing central nervous system inflammation, with slight impairment
      of the blood-brain barrier. These soluble adhesion molecules may be clinically
      useful as indicators of this inflammatory process and may provide some insight
      into this enigmatic disease process.

PMID- 11841723
TI  - Working area and angle of attack in three cranial base approaches: pterional,
      orbitozygomatic, and maxillary extension of the orbitozygomatic approach.
AB  - OBJECTIVE: This study was designed to quantify the operative exposure obtained in
      the pterional, orbitozygomatic, and modified orbitozygomatic with maxillary
      extension surgical approaches. METHODS: The pterional and orbitozygomatic
      approaches and a variation of the orbitozygomatic osteotomy that included an
      extra centimeter of bone resection in the inferior direction ("maxillary
      extension") were performed on cadaveric heads. For each surgical exposure, the
      working area was determined by using triangles defined with anatomic points. The
      "angle of attack" of the approaches for the same target point was determined with
      the use of a robotic microscope. RESULTS: The maximum allowable angle of attack
      was significantly greater with the orbitozygomatic approach (37.2 +/- 4.7
      degrees) than that with the pterional approach (27.1 +/- 4.3 degrees) (P <
      0.001). The angle of attack with the maxillary extension (42.0 +/- 4.9 degrees)
      was significantly greater than that with the orbitozygomatic approach (P <
      0.001). The working areas were 281, 343, and 371 mm(2) for the pterional,
      orbitozygomatic, and maxillary extension approaches, respectively. The
      orbitozygomatic approach with maxillary extension had a significantly larger
      working area than the pterional approach (P = 0.011). CONCLUSION: Increments in
      bony removal open a wider angle in which to work more than they increase the
      actual amount of working area. Increasing the amount of bone removed by using an
      orbitozygomatic approach instead of a pterional approach converts a narrow space
      into a wide portal, allowing surgeons to work closer to the surgical target while
      decreasing the need for brain retraction. Extending the orbitozygomatic approach
      into the maxillary region also improves the exposure area and angle, but less
      significantly.

PMID- 11841724
TI  - Ophthalmic segment aneurysm surgery.

PMID- 11841725
TI  - Microsurgical anatomic features of the lamina terminalis.
AB  - OBJECTIVE: The lamina terminalis (LT) is a structure of considerable interest for
      microneurosurgery, and precise knowledge regarding its normal anatomic features
      and the variations thereof is required. The purpose of this study, which was
      based on microanatomic dissection of human cadaveric specimens, was to review the
      microsurgical anatomic features of the LT and its neurovascular relationships.
      The surgical implications of the morphometric data are discussed. METHODS: The
      region of the LT was examined in 10 human cadaveric heads, obtained from 8 fresh
      adult cadavers and 2 formalin-fixed adult cadavers, and in 10 formalin-fixed,
      isolated, adult brains. An operating microscope was used for all dissections and
      measurements. RESULTS: Assuming the LT to be a triangular structure, we performed
      measurements of the distance between the midportion of the upper edge of the
      chiasm and the lower edge of the anterior commissure (height), which averaged
      8.25 mm. The distance between the medial edges of the optic tracts (base)
      averaged 12.81 mm. The area averaged 52.84 mm(2). A minimal amount of retraction
      was needed to fully expose the LT, and generally there was no need to mobilize
      the anterior cerebral artery-anterior communicating artery complex. Perforating
      branches to the hypothalamus and optic apparatus are laterally located and do not
      interfere with LT incision and/or fenestration. CONCLUSION: The LT constitutes a
      clearly identifiable microsurgical target. The allowable extent of LT opening is
      sufficient to provide wide access into and free cerebrospinal fluid flow from the
      third ventricle. Fenestration of the LT is a safe procedure, provided that the
      relevant anatomic landmarks are identified and respected.

PMID- 11841726
TI  - Predictive values of beta-trace protein (prostaglandin D synthase) by use of
      laser-nephelometry assay for the identification of cerebrospinal fluid.
AB  - OBJECTIVE: beta-Trace protein (beta-TP) is an immunological marker for the
      detection of cerebrospinal fluid traces. The aim of the study was to evaluate the
      predictive values of a new research assay for beta-TP. METHODS: A total of 154
      specimens from patients with otorrhea or rhinorrhea were investigated for
      cerebrospinal fluid (CSF) by use of a laser-nephelometric assay for beta-TP.
      Samples were obtained between January 1994 and November 2000. A sample was
      reported to be positive for CSF when the beta-TP concentration was more than 6
      mg/L. Case evaluations were performed retrospectively and tabulated for
      indication, clinical course, additional investigations, surgical procedure, and
      follow-up. RESULTS: beta-TP was detected in 16 specimens; 138 samples were
      negative for beta-TP with a value less than 3 mg/L. One sample was suggestive of
      CSF traces at 4.6 mg/L. In correlation with the clinical course, the
      intraoperative findings, intraoperative visualization with sodium fluorescein,
      high-resolution computed tomography of the paranasal sinuses or the petrous bone,
      computed tomographic cisternography, magnetic resonance imaging, and radionuclide
      cisternography, there was no false-positive result. On four occasions, false
      negative results occurred, with an overall accuracy of 0.974. The beta-TP test
      had a negative predictive value of 0.971 and a positive predictive value of 1.
      CONCLUSION: Analysis of betas-TP via the nephelometric assay is a valuable and
      reliable test in cranial base surgery for the identification of CSF.

PMID- 11841727
TI  - SI-27, a novel inhibitor of matrix metalloproteinases with antiangiogenic
      activity: detection with a variable-pressure scanning electron microscope.
AB  - OBJECTIVE: Degradation of basement membrane is one the of crucial steps in tumor
      angiogenesis and is performed by matrix metalloproteinases (MMPs). This study was
      designed to investigate the suppression of tumor angiogenesis by SI-27, an MMP
      inhibitor. METHODS: SI-27 was applied at noncytotoxic concentrations (1-100
      micromol/L), and its effect on nonmitogenic vascular endothelial growth factor
      (VEGF)-enhanced cell motility and in vitro angiogenesis by human umbilical vein
      endothelial cells was determined. The activity of MMP-1, MMP-2, and tissue
      inhibitor of metalloproteinase 1 was determined by enzyme-linked immunosorbent
      assay. The effect of SI-27 on in vitro angiogenesis stimulated by supernatants of
      human glioma cell lines (U87MG, U251MG, and U373MG) also was examined.
      Angiogenesis was detected with variable vacuum scanning electron microscopy.
      RESULTS: Cell motility and in vitro angiogenesis by human umbilical vein
      endothelial cells were significantly increased by VEGF. The maximal effect on
      cell motility by VEGF was noted at 5 ng/ml (P < 0.001), and the maximal effect on
      the capillary network was observed at 10 ng/ml (P < 0.001), along with elevated
      MMP-1 and MMP-2 activity. Whereas SI-27 significantly suppressed VEGF-mediated in
      vitro angiogenesis (50 micromol/L; P < 0.001) and inactivated both MMP-1 and MMP
      2, the expression of tissue inhibitor of metalloproteinase 1 and VEGF-mediated
      cell motility were not affected by SI-27. The angiogenesis promoted by glioma
      supernatants showed a significant reduction in the presence of SI-27 (10
      micromol/L; U87MG, P < 0.01; U251MG, P < 0.01; U373MG, P < 0.01). CONCLUSION: SI
      27 inhibited in vitro tumor angiogenesis by suppression of MMP. This agent may be
      anticipated to prevent tumor growth through an angiosuppressive effect.

PMID- 11841728
TI  - Intraventricular infusion of vascular endothelial growth factor promotes cerebral
      angiogenesis with minimal brain edema.
AB  - OBJECTIVE: Therapeutic cerebral angiogenesis, i.e., using angiogenic factors to
      enhance collateral vessel formation within the central nervous system, is a
      potential method for cerebral revascularization. Vascular endothelial growth
      factor (VEGF) is a potent endothelial cell mitogen that also increases capillary
      permeability, particularly in ischemic tissue. The purpose of this study was to
      assess the angiogenic and capillary permeability effects of chronic
      intraventricular infusion of exogenous VEGF in nonischemic brain tissue, because
      many patients with impaired cerebrovascular reserve do not exhibit chronic
      cerebral ischemia. METHODS: Recombinant human VEGF(165) was infused into the
      right lateral ventricle of rats at a rate of 1 microl/h for 7 days, at
      concentrations of 1 to 25 microg/ml, with osmotic minipumps. Control animals
      received vehicle only. Vessels were identified in laminin immunohistochemical
      analyses. Capillary permeability and brain edema were assessed with Evans blue
      extravasation, [(3)H]inulin permeability, and brain water content measurements.
      RESULTS: Vessel density was dose-dependently increased by VEGF(165) infusions,
      with significant increases occurring in animals treated with 5 or 25 microg/ml,
      compared with control animals (P h 0.01). Significant enlargement of the lateral
      ventricles was observed for the highest-dose group but not for animals treated
      with other doses. Capillary permeability was assessed in animals treated with a
      dose of 5 microg/ml. An increase in capillary permeability in the diencephalon
      was identified with Evans blue extravasation and [(3)H]inulin permeability
      assessments; however, the brain water content was not significantly increased.
      CONCLUSION: Chronic intraventricular infusions of VEGF(165) increased vascular
      density in a dose-dependent manner. There seems to be a therapeutic window,
      because infusion of VEGF(165) at a concentration of 5 microg/ml resulted in a
      significant increase in vessel density with minimal associated brain edema and no
      ventriculomegaly.

PMID- 11841729
TI  - A herpes simplex virus type 1 mutant with gamma 34.5 and LAT deletions
      effectively oncolyses human U87 glioblastomas in nude mice.
AB  - OBJECTIVE: We previously constructed a novel recombinant herpes simplex virus
      with deletions in the gamma 34.5 and LAT genes. LAT was replaced by the gene for
      green fluorescent protein, to allow monitoring of viral transduction in vitro and
      in vivo. We previously confirmed that this virus, designated DM33, retains its
      oncolytic properties in vitro and is inhibited with respect to spontaneous
      reactivation. The objective of this study was to demonstrate the therapeutic
      efficiency of this virus in the treatment of human gliomas in nude mice. METHODS:
      Thirty BALB/c nude mice underwent stereotactic implantation of U-87 MG gliomas in
      the right corpus striatum. Subsequently, mice received intratumoral inoculations
      of either DM33 (n = 20) or virus-free medium (n = 10). Ten mice given injections
      of DM33 were also treated intraperitoneally with ganciclovir. RESULTS:
      Intratumoral administration of DM33 to nude mice bearing intracranial U-87 MG
      human gliomas prolonged survival times, compared with saline-treated control
      animals (P < 0.05). Histological analyses of treated tumors demonstrated
      decreased tumor size and tumor cell lysis. Control tumors averaged 7.05 +/- 0.83
      mm(2) (mean +/- standard error), whereas the average for the DM33 group was 4.61
      +/- 1.57 mm(2) and that for the DM33 plus ganciclovir group was 2.49 +/- 1.32
      mm(2). The difference in tumor sizes between the control group and the DM33 plus
      ganciclovir group was statistically significant (P = 0.044). Viral infection was
      limited to the tumors, and replication was not observed in normal neurons or
      glia. CONCLUSION: The efficacy of this virus in the treatment of experimental
      gliomas, its safety (as confirmed by its inability to reactivate), and its
      attenuated neurovirulence make DM33 a promising oncolytic agent for glioma
      therapy.

PMID- 11841730
TI  - Sir Victor Horsley (1857-1916): pioneer of neurological surgery.
AB  - Immortalized in surgical history for the introduction of "antiseptic wax," Sir
      Victor Horsley played a pivotal role in shaping the face of standard
      neurosurgical practice. His contributions include the first laminectomy for
      spinal neoplasm, the first carotid ligation for cerebral aneurysm, the curved
      skin flap, the transcranial approach to the pituitary gland, intradural division
      of the trigeminal nerve root for trigeminal neuralgia, and surface marking of the
      cerebral cortex. A tireless scientist, he was a significant player in discovering
      the cure for myxedema, the eradication of rabies from England, and the invention
      of the Horsley-Clarke stereotactic frame. As a pathologist, Horsley performed
      research on bacteria and edema and founded the Journal of Pathology. Horsley's
      kindness, humility, and generous spirit endeared him to patients, colleagues, and
      students. Born to privilege, he was nonetheless dedicated to improving the lot of
      the common man and directed his efforts toward the suffrage of women, medical
      reform, and free health care for the working class. Knighted in 1902 for his many
      contributions to medicine, Sir Victor met an untimely death during World War I
      from heat stroke at the age of 59. An iconoclast of keen intellect, unlimited
      energy, and consummate skill, his life and work justify his epitaph as a "pioneer
      of neurological surgery."

PMID- 11841731
TI  - Bilateral metachronous germinoma of the basal ganglia occurring long after total
      removal of a mature pineal teratoma: case report.
AB  - OBJECTIVE AND IMPORTANCE: We report the extremely rare occurrence of a second
      germ cell tumor at a different site and with different histological types long
      after total removal of a mature pineal teratoma. CLINICAL PRESENTATION: A 10-year
      old boy who presented with headache and vomiting was admitted to our hospital.
      Neuroradiological studies revealed a tumor in the pineal region. The tumor was
      totally removed. Histologically, the tumor proved to be a mature teratoma. The
      patient's postoperative course was uneventful. The patient received no adjuvant
      therapy and was followed in the outpatient clinic. Three years later, he was
      readmitted with transient left upper limb weakness and vomiting.
      Neuroradiological studies showed a tumor in the bilateral basal ganglia.
      INTERVENTION: The second tumor, which was located in the right basal ganglion,
      was partially removed for biopsy. Histologically, the tumor proved to be a
      germinoma. The patient received three cycles of combination chemotherapy
      consisting of carboplatin and etoposide with radiotherapy. After the second
      course of chemotherapy, magnetic resonance imaging studies revealed no evidence
      of the tumor. CONCLUSION: The second tumor was considered to be a de novo
      metachronous neoplasm rather than a recurrence of the original mature teratoma.
      We think that if primordial germ cell groups exist along the midline of the
      brain, more than two primordial germ cell groups could give rise to metachronous
      neoplasms at different sites and with different histological types.

PMID- 11841732
TI  - Suprasellar adrenocorticotropic hormone-secreting ectopic pituitary adenoma: case
      report and literature Review.
AB  - OBJECTIVE AND IMPORTANCE: Functional ectopic pituitary adenomas are rare and can
      be misdiagnosed as extensions of pituitary adenomas when they are located in the
      vicinity of the normal gland. In this report, we present a case of an ectopic
      adrenocorticotropic hormone-secreting suprasellar pituitary adenoma that caused
      Cushing's disease. A literature review of previously reported ectopic pituitary
      adenomas is included to illustrate the diverse clinical manifestations of this
      disease entity. CLINICAL PRESENTATION: An 11-year-old boy was noted to have
      hirsutism, a buffalo hump, and unexplained weight gain consistent with Cushing's
      syndrome. Laboratory investigations revealed that the boy had elevated
      adrenocorticotropic hormone and serum cortisol levels unsuppressed by
      dexamethasone. Magnetic resonance imaging scans were suggestive of a pituitary
      adenoma with suprasellar extension. INTERVENTION: The initial transsphenoidal
      approach failed to achieve complete surgical resection. A repeat operation in
      which the pterional approach was used revealed a suprasellar pituitary adenoma
      without association with intrasellar contents. The patient's cushingoid symptoms
      improved significantly 3 months after surgery. CONCLUSION: Ectopic pituitary
      adenomas should be considered in the differential diagnosis for all patients with
      Cushing's syndrome. Furthermore, surgical approaches should be chosen carefully
      once the diagnosis of ectopic pituitary adenoma is made.

PMID- 11841733
TI  - Cerebellopontine angle lipomas: report of four cases and review of the
      literature.
AB  - OBJECTIVE: To define the management of internal acoustic meatus and
      cerebellopontine angle (CPA) lipomas according to their clinical, histological,
      and surgical characteristics. METHODS: We report four new cases of CPA lipomas
      diagnosed in the Department of Otorhinolaryngology-Head and Neck Surgery of
      Hopital Pitie-Salpetriere and review 94 cases reported previously in the
      literature. RESULTS: Lipomas represented 0.14% of CPA and internal acoustic
      meatus tumors. Localization was on the left side in 59.9%, on the right side in
      37%, and bilateral in 3.1% of the patients. The diagnosis was confirmed
      radiologically in 33 of 98 patients, surgically in 60 patients, and by autopsy in
      5 patients. The most frequent associated symptoms were of cochleovestibular
      origin, such as hearing loss (62.2%), dizziness (43.3%), and unilateral tinnitus
      (42.2%). Other associated symptoms involved the facial nerve (9%) or the
      trigeminal nerve (14.4%). Complete resection was performed in only 32.8% of the
      patients with frequent cranial nerve involvement. Frequent cranial nerve
      involvement was seen in 95.4% of all patients. After surgery, patient
      symptomatology was unchanged in 9.2% of the patients, and 50% were improved;
      however, new postoperative deficits occurred in two-thirds of the patients.
      Overall, 72.2% of the patients experienced new postoperative deficits such as
      hearing loss (64.8%). Preservation of hearing was possible in only 26% of the
      patients. Only 18% of patients were improved after surgery without any new
      postoperative deficits. CONCLUSION: Preoperative diagnosis of internal acoustic
      meatus/CPA lipomas is based on magnetic resonance imaging. The aim of surgery in
      these cases is not tumor removal but cranial nerve decompression or vestibular
      transection, and surgery is performed only in patients with disabling and
      uncontrolled symptoms.

PMID- 11841734
TI  - Intracranial trigeminal neuroma involving the infratemporal fossa: case report
      and review of the literature.
AB  - OBJECTIVE AND IMPORTANCE: Intracranial trigeminal neuroma extending
      extracranially is not a common finding. We report the case of a patient with a
      right cystic trigeminal neuroma arising in the middle temporal fossa and
      infratemporal areas. The clinical, radiological, and intraoperative features of
      these unusual lesions are discussed, and the relevant literature is reviewed.
      CLINICAL PRESENTATION: A 35-year-old woman presented with a 4-year history of
      right serous otitis media associated with recent right facial paresthesia. A
      neurological examination revealed hypesthesia in the mandibular division of the
      right trigeminal nerve. Computed tomographic and magnetic resonance imaging scans
      demonstrated a 6 x 6 x 4-cm well-enhancing cystic mass arising from the middle
      temporal fossa and extending extracranially to the infratemporal fossa through
      the enlarged foramen ovale. INTERVENTION: The tumor was extradural and originated
      from the right mandibular nerve. It was subtotally removed via a subtemporal
      intradural and extradural approach. A pathological examination revealed a cystic
      neuroma. The patient has remained well during 12 months of follow-up, and no
      evidence of recurrence has been noted on magnetic resonance imaging studies.
      CONCLUSION: Unilateral serous otitis media by obstruction of the eustachian tube
      is a rare initial manifestation of trigeminal neuroma. We emphasize the benefit
      of neuroradiological examinations (both computed tomographic scanning and
      magnetic resonance imaging), which provided the clearest preoperative
      localization of this large intra- and extracranial tumor. A combined
      frontotemporal and infratemporal fossa approach is preferred, considering the
      difficulty of surgical removal. The prognosis for most patients was good. Twenty
      five previously reported cases were also reviewed.

PMID- 11841735
TI  - Ectopic recurrence of craniopharyngioma after an interhemispheric transcallosal
      approach: case report.
AB  - OBJECTIVE AND IMPORTANCE: Ectopic recurrence of a craniopharyngioma is a rare
      postoperative complication. We present a case of a craniopharyngioma that
      ectopically recurred along the tract of a previous surgical route. CLINICAL
      PRESENTATION: A 73-year-old female patient presented 8 years earlier with a
      suprasellar craniopharyngioma. She underwent a right frontal craniotomy, with an
      interhemispheric transcallosal approach, for total microsurgical resection of the
      tumor. No postoperative radiotherapy was administered. Four years after surgery,
      magnetic resonance imaging studies revealed a well-circumscribed, heterogeneously
      enhancing, parasagittal mass with significant vasogenic edema in the right
      frontal lobe. Enlargement of the lesion was noted in subsequent radiological
      evaluations until 8 years after surgery, when the patient experienced a
      significant decline in neurocognitive status and the mass was surgically
      resected. INTERVENTION: Gross total resection of a histologically confirmed
      craniopharyngioma was achieved. CONCLUSION: To our knowledge, only eight previous
      case reports described the ectopic recurrence of a craniopharyngioma.
      Transplantation of tumor cells along the tract of a previous surgical route in
      six cases and dissemination in cerebrospinal fluid in two cases are presumed to
      be the primary mechanisms by which these ectopic recurrences occurred. The
      results of our literature review led us to conclude that total surgical
      resection, combined with careful inspection and irrigation of the surgical field,
      is the optimal treatment for preventing ectopic recurrences. Furthermore, it is
      recommended that, after primary craniopharyngioma resection, patients undergo
      long-term clinical and radiological follow-up monitoring for the rare development
      of an ectopically recurring tumor.

PMID- 11841736
TI  - De novo development of a cavernous malformation of the brain: significance of
      factors with paracrine and endocrine activity: case report.
AB  - OBJECTIVE AND IMPORTANCE: De novo development of cavernous malformations is
      poorly documented in the literature. CLINICAL PRESENTATION: We report the case of
      a 37-year old woman with de novo growth of a cavernous malformation of the brain.
      The patient presented with a 12-month history of nonspecific headaches and
      paresthesias after two pregnancies. After computed tomographic scanning of the
      cranium, a cavernous malformation located parieto-occipitally within the right
      brain hemisphere was diagnosed. Control magnetic resonance imaging scans obtained
      12 years earlier did not reveal a similar lesion. INTERVENTION: Surgery was
      performed, and the specimen was analyzed histopathologically. CONCLUSION:
      Immunohistochemistry demonstrated lack of expression of pituitary hormones as
      well as of androgen, estrogen, and progesterone hormone receptors. However,
      strong expression of both basic fibroblast growth factor and CD44 was detected in
      surrounding tissue, and expression of CD44 was noted within the matrix of the
      cavernous malformation.

PMID- 11841737
TI  - Tuberculoma of the conus medullaris: case report.
AB  - OBJECTIVE AND IMPORTANCE: Intramedullary spinal tuberculoma is a rare form of
      central nervous system tuberculosis. This article describes an affected patient
      who presented with left leg paresis. CLINICAL PRESENTATION: A 46-year-old man
      presented with a 7-day history of left leg weakness. The patient's medical
      history included infection with pulmonary tuberculosis 15 years previously, at
      which time he had been treated with antituberculosis therapy. The neurological
      examination performed at admission revealed left leg paresis with Grade 2/5 power
      in all muscle groups. The patient reported no urinary or bowel problems.
      INTERVENTION: Surgery was performed with the patient in the prone position. The
      procedure involved laminectomies at T11, T12, and L1, followed by a midline
      myelotomy. The mass was excised completely. Histopathological examination
      revealed a granulomatous lesion that contained Langhans' giant cells,
      inflammatory cells, and evidence of caseating necrosis. The patient was
      prescribed a 6-month course of antituberculosis therapy with pyrazinamide,
      isoniazid, and rifampin. CONCLUSION: The outcome was favorable. Recently, a
      number of authors have reported success with medical management of intraspinal
      tuberculoma. Intraspinal tuberculoma produces a mass effect that can jeopardize
      spinal cord function. The optimal treatment is a combination of microsurgical
      resection and antituberculosis chemotherapy.

PMID- 11841738
TI  - Intradural hemangiopericytoma of the lumbar spine: case report.
AB  - OBJECTIVE AND IMPORTANCE: Hemangiopericytoma is a rare tumor of the central
      nervous system, most often found supratentorially. Thirty-nine cases within the
      spinal column, of which five were intradural, have been reported. To date, no
      magnetic resonance imaging descriptions of intradural hemangiopericytomas have
      been published. This article is the first report of an intradural
      hemangiopericytoma of the lumbar spine and the first magnetic resonance imaging
      description of such a lesion. CLINICAL PRESENTATION: A 31-year-old man presented
      with progressive bilateral leg paresthesia and increased lower extremity cramping
      and fatigue during a period of several months. This progressed to urinary
      urgency, frequency, and sexual dysfunction. A neurological examination revealed
      no motor or sensory deficits. Gadolinium-enhanced magnetic resonance imaging of
      the lumbar spine revealed a centrally located intradural mass posterior to the L4
      vertebral body. TECHNIQUE: The patient underwent a laminectomy of L4 and partial
      laminectomy of L3 with complete en bloc resection of the tumor. A discrete,
      intradural, red-appearing lesion was found and resected en bloc. Pathological
      findings were consistent with hemangiopericytoma. CONCLUSION: Intradural
      hemangiopericytomas, although rare, cannot be differentiated from other, more
      benign tumors. Spinal hemangiopericytomas ideally should be resected en bloc to
      reduce operative blood loss and potentially increase disease-free survival time.
      Despite total surgical resection of these benign-seeming lesions, the high
      recurrence rate mandates close follow-up and consideration of adjuvant therapy.

PMID- 11841739
TI  - Treatment of an iatrogenic petrous carotid artery pseudoaneurysm with a Symbiot
      covered stent: technical case report.
AB  - OBJECTIVE AND IMPORTANCE: Surgery involving the middle ear or the temporal bone
      may cause an injury to the petrous carotid artery resulting in a pseudoaneurysm.
      Conventional treatment of such pseudoaneurysms has ranged from carotid occlusion
      to conservative management. The use of a balloon-expandable stent and/or
      Guglielmi detachable coils may be effective in a partially healed pseudoaneurysm.
      This report details the case of an acute petrous carotid pseudoaneurysm after a
      myringotomy procedure that was effectively treated with an expanded
      polytetrafluoroethylene-covered stent. CLINICAL PRESENTATION: During a right
      myringotomy procedure, pulsatile blood was encountered in a 42-year-old woman
      with a history of repeated ear infections and bilateral middle ear ventilation
      tube placement. The blood was adequately tamponaded with gauze packing. Computed
      tomography of the temporal bone demonstrated a dehiscent carotid artery, and
      cerebral angiography revealed a 6-mm right petrous carotid pseudoaneurysm.
      INTERVENTION/TECHNIQUE: An 8-French guide catheter was positioned via a
      transfemoral approach into the cervical right internal carotid artery, and the
      patient was systemically heparinized. A 4- x 31-mm Symbiot covered stent (Boston
      Scientific/Scimed, Maple Grove, MN) was passed over a Choice PT exchange wire
      (Boston Scientific/Scimed) to cover the neck of the pseudoaneurysm, obliterating
      the pseudoaneurysm. The patient was given aspirin and clopidogrel after stenting,
      and ear exploration was possible later the same day. Follow-up computed
      tomographic angiography performed 6 weeks later verified patency of the stent.
      CONCLUSION: The use of an expanded polytetrafluoroethylene-covered stent may
      effectively treat intracranial internal carotid artery pseudoaneurysms in an
      acute setting. This treatment allows preservation of the parent artery and
      immediate treatment by reconstruction of the incompetent arterial wall to prevent
      potentially life-threatening hemorrhagic complications.

PMID- 11841740
TI  - Extracranial-intracranial vein graft bypass for giant intracranial aneurysm
      surgery for pediatric patients: two technical case reports.
AB  - OBJECTIVE AND IMPORTANCE: Herein we describe two cases of extracranial
      intracranial vein graft bypasses for the treatment of giant intracranial
      aneurysms in prepubertal pediatric patients. One patient is, we think, the
      youngest patient reported in the literature to have been successfully treated in
      such a manner, with a good long-term outcome. Such grafts seem to enlarge
      longitudinally during the growth spurt, making such techniques reasonable long
      term therapeutic options for the management of complex intracranial aneurysms in
      pediatric patients. CLINICAL PRESENTATION: Patient 1, a 13-year-old boy,
      presented with headaches and rapidly progressive right cavernous sinus syndrome.
      Computed tomography and cerebral angiography revealed a giant, fusiform, right
      intracavernous internal carotid artery aneurysm. Patient 2, a 23-month-old girl,
      was discovered to harbor an asymptomatic, recurrent, giant, fusiform, left M1
      middle cerebral artery aneurysm 1 year after presenting with seizures related to
      subarachnoid hemorrhage from the aneurysm, for which she had been treated with
      clipping and an M2-M2 anastomosis. INTERVENTION: Both patients underwent
      craniotomies, with sacrifice of the proximal parent vessel (the distal cervical
      internal carotid artery and the proximal middle cerebral artery, respectively),
      combined with cerebral revascularization through extracranial-intracranial
      saphenous vein bypass grafts. Both patients experienced excellent long-term
      clinical outcomes, have undergone significant growth, and exhibit excellent long
      term graft patency and aneurysm obliteration. CONCLUSION: These two cases
      highlight the safety and efficacy of extracranial-intracranial vein graft
      bypasses among prepubertal pediatric patients. The indications for bypass
      procedures to treat giant intracranial aneurysms are discussed, and the technical
      aspects of maximizing vein bypass graft patency are reviewed.

PMID- 11841741
TI  - The sizer-dissector for aneurysm clip selection: technical note.
AB  - OBJECTIVE: Appropriate clip selection frequently becomes a matter of trial and
      error because of inadequate dissection of the pathway for each clip blade. To
      facilitate selection of the proper clip size, a series of dissectors have been
      designed that mimic the exact caliber of each category of Sugita clips. METHODS:
      Three lines of sizer-dissectors reflecting the wire size of the most commonly
      used Sugita clips were developed by attaching a single aneurysm clip blade to a
      rounded microdissector handle. Each sizer-dissector is scaled in millimeters and
      is available in straight and angled configurations. Once dissection is presumed
      to be complete, the device is passed through the pathway of the intended aneurysm
      clip blades, and the clip with the appropriate caliber and length for permanent
      occlusion is selected. RESULTS: During dissection and clip ligation of 83
      aneurysms, the sizer-dissector was used to select the blade length in 16 lesions
      and the blade caliber in 5 lesions. There were no complications associated with
      deployment of the device. CONCLUSION: By use of the sizer-dissector before
      attempting clip placement, clip selection is facilitated, safety is enhanced, and
      clip wastage is reduced.

PMID- 11841742
TI  - Implantation of a reservoir for refractory chronic subdural hematoma.

PMID- 11841743
TI  - Treatment of temporomandibular joint ankylosis: a case report.
AB  - Bony ankylosis of the temporomandibular joint (TMJ) in a male patient was not
      diagnosed until the patient reached his early teens, at which time the condition
      was treated with a costochondral graft. At the time of treatment, there was an
      expectation that further orthognathic surgery would be required to correct the
      skeletal deformity. However, with the release of the ankylosis and growth of the
      costochondral graft, a good functional and esthetic result was achieved without
      further surgery. It is important that family dentists be aware of the clinical
      signs and symptoms of TMJ ankylosis, to allow early diagnosis and treatment.

PMID- 11841745
TI  - Arteriovenous malformation of the mandible: review of literature and case
      history.
AB  - Vascular malformations of the jaws can lead to disastrous complications, but
      there seems to be no consensus as to their treatment. The literature presents the
      pathophysiology and clinical aspects of these lesions, as well as the divergent
      views of the authors. Treatment by catheterization and embolization, with direct
      transosseous injection of cyanoacrylate, appears to be the least harmful and most
      permanent treatment in certain conditions, as evidenced by the case of this 9
      year-old patient having a high-flow mandibular vascular malformation

PMID- 11841744
TI  - The epidemiology of mandibular fractures treated at the Toronto general hospital:
      A review of 246 cases.
AB  - BACKGROUND: Mandibular fractures constitute a substantial proportion of cases of
      maxillofacial trauma. This study investigated the incidence, causes and treatment
      of mandibular fractures at a hospital in Toronto. METHODS: The medical records
      and radiographs for 246 patients treated for mandibular fracture at the Toronto
      General Hospital over a 51 2-year period (from 1995 to 2000) were reviewed. Data
      on the patients age, sex, smoking status, alcohol and drug use, mechanism of
      injury, treatment modality, and post-operative complications were recorded and
      assessed. RESULTS: Men 21 to 30 years of age sustained the most mandibular
      fractures. The ratio of males to females was 5:1. Most fractures were caused by
      violent assault (53.5%), followed by falls (21.5%) and sports activities (12.2%).
      Alcohol was a contributing factor at the time of injury in 20.6% of fractures for
      which this information was available. Nearly half of all cases were treated by
      open reduction (49.1%). Complications occurred in 5.3% of patients. CONCLUSION:
      The incidence and causes of mandibular fracture reflect trauma patterns within
      the community and, as such, can provide a guide to the design of programs geared
      toward prevention and treatment.

PMID- 11841746
TI  - Obstructive sleep apnea syndrome: diagnosis and management.
AB  - Increased awareness that changes in sleeping habits and daytime behaviour may be
      attributable to obstructive sleep apnea syndrome (OSAS) has led many patients to
      seek both information and definitive treatment. The purpose of this article is to
      provide information to dentists that will enable them to identify patients who
      may have OSAS and to assist these patients in making informed decisions regarding
      treatment options. In patients who have identifiable anatomic abnormalities of
      the maxilla and mandible resulting in a narrow pharyngeal airway, orthognathic
      surgery appears to be an excellent treatment option.

PMID- 11841747
TI  - Nodular fasciitis in the oral cavity.
AB  - Rapidly growing soft-tissue lesions in the oral and maxillofacial region can
      represent a variety of diagnoses involving radically different treatment
      modalities. Accurate diagnosis is important to avoid unnecessary and often
      mutilating surgery. Nodular fasciitis is a rapidly proliferating fibroblastic
      lesion that presents as a tumour-like mass. Although up to 20% of cases occur in
      the head and neck region, lesions of the oral cavity are extremely rare. A case
      of oral nodular fasciitis is described, and a review of the literature is
      presented.

PMID- 11841748
TI  - Cleft lip and palate: a review for dentists.
AB  - The goals of primary closure of cleft lip and palate include not only re
      establishing normal insertions for all of the nasolabial muscles but also
      restoring the normal position of all the other soft tissues, including the
      mucocutaneous elements. Conventional surgical wisdom, which recommends waiting
      until growth is complete before undertaking surgical correction of the
      postoperative sequelae of primary cheiloplasty, carries with it many
      disadvantages. If, after primary surgery of the lip, orolabial dysfunctions
      remain, they will exert their nefarious influences during growth and will
      themselves lead to long term dentofacial imbalances. These imbalances can
      significantly influence facial harmony. Unless accurate, symmetric and functional
      reconstruction of the nasolabial muscles is achieved during the primary surgery,
      not only will the existing dentoskeletal imbalances be exaggerated, but other
      deformities will be caused during subsequent growth, among which the most
      important are nasal obstruction and mouth breathing, reduced translation of the
      maxilla, dysymmetry of the nose and inability of the patient to symmetrically
      project the upper lip

PMID- 11841750
TI  - [Change in Latin-American health systems and future perspectives].

PMID- 11841751
TI  - [Challenges to Latin-American health systems: what can be learned from the
      European experience?].
AB  - This article compares the challenges of health systems in Latin America and the
      experience in Europe. The framework is the analysis of four functions: a) to
      generate resources; b) to produce activities; c) to finance, and d) to exercise
      stewardship. It is at this level where actors can influence health system
      responsiveness. Five challenges are identified in Latin America: a) to extend
      (prepayment and solidarity) financial protection; b) to stabilise that protection
      for crisis times; c) to equilibrate resources in accordance to capacity for
      financing services; d) to increase efficiency (technical and of placement) to
      produce services, and e) to improve the stewardship function in public and
      private sectors (the most important and difficult challenge Latin-American
      systems have nowadays). The experience of reform in Europe is analysed, showing:
      a) experiences about financial protection in Beveridge and Bismarck systems; b)
      stability in crisis times, recently confirm (West) and with important obstacles
      (East); c) efforts to equilibrate hospital beds and health care professionals,
      combining regulation and incentives; d) increase of efficiency in services
      production, with more express prioritisation, empowering patients, decentralising
      management and with market incentives, and e) improvement of stewardship with
      better (not less, sometimes even more) regulation. Three areas of European
      experience stand out: a) to combine solidarity with financial sustainability; b)
      to introduce market incentives in a measured way, but maintaining a clear
      stewardship role for the state, and c) to adopt innovations in organising and
      producing services. In spite of methodological difficulties, convergence of
      challenges and adopted solutions justify this analysis, but learning must be seen
      in each national context. A future article will analyse lessons offered by reform
      in Latin-American systems for European reforms.

PMID- 11841752
TI  - [Decentralization of the health sector in Latin America].
AB  - This paper analyzes the Latin American experience of decentralizing health
      services within the context of health reform. We examine the meaning of the term
      decentralization and discuss the various modalities of this concept:
      geographical, institutional and functional. The objectives that, in general,
      these objectives have not been achieved. After reviewing the literature and
      drawing on our own fieldwork, we conclude that in many instances the Latin
      American decentralization programs have produced results opposite to those
      intended, i.e., these programs have increased inequality and the cost of services
      and have reduced efficiency and quality of care. We point out that existing
      information is insufficient to determine with exactitude whether the failure of
      decentralization is due to the selection of inappropriate policies or to failures
      in the implementation process. Decentralization is a complex political process,
      policy makers should decide on the modality of decentralization they wish to
      implement, estimate the costs, identify the potential obstacles that could
      surface during the implementation phase and provide solutions. We conclude by
      suggesting that the multilateral banks have erred by pressing governments to
      improvise the implementation of decentralization programs without taking into
      account the different historical, political and socioeconomic contexts.

PMID- 11841753
TI  - [The reform process and social participation in health in Latin America].
AB  - Currently, many countries throughout the world are reforming their health
      services. Even though these reforms differ according to the country's
      characteristics, they share many policies, one of which is the promotion of
      social participation in health-related matters. This policy, however, is not new
      in the field of health service organization. Throughout the last century,
      individual or collective collaboration between the population and health services
      has been promoted by several philosophies and concepts with different aims: from
      the search for collaboration with the general public to broaden public health
      system coverage to the promotion of the creation of mechanisms that would allow
      society to exercise control over these services' performance. Nevertheless, for
      the public to be involved with these services, several factors concerning both
      the services themselves and the population, need to converge. Although the
      theoretical frameworks that have encouraged social participation throughout the
      history of the development of health systems differ considerably, their practical
      implementation shares many common elements in all periods, from participation as
      a means of obtaining certain objectives to being an end in itself, as a
      democratic process. This can also be applied to the current promotion of social
      participation policies in the context of health care reforms, which are analyzed
      using Colombia and Brazil as examples.

PMID- 11841754
TI  - [Health reform and its political component: a feasibility analysis].
AB  - The political dimension of the health reform is a fundamental aspect that not
      only influences the project's feasibility, but also its form and content.
      Therefore the study of the political aspects involved in the health reform
      process is essential to determine the political feasibility of the reform. Based
      on the case studies of Colombia and Mexico, this study concentrates on the
      State's capability to promote health reform projects successfully. It
      specifically focuses on those elements that seek to improve the political
      feasibility of formulating, legislating and implementing reform proposals. The
      relevant variables under study are: the institutional context in which the reform
      initiatives develop; the political dynamic of the reform process; and the
      characteristics and strategies of the teams in charge of leading the reforms
      (change teams). The similarities in the political strategies used by the teams in
      charge of the health reform, and those of similar technocratic teams in charge of
      economic reform, stand out as one the study's main findings. It is argued that,
      although these strategies were effective in bringing about the creation of new
      actors in the health sector such as private organizations for the financing and
      provision of health services, they did not have the same impact on the
      transformation of the old actors the health ministries and the social security
      institutes, therefore considerably limiting the scope of the reforms.

PMID- 11841755
TI  - [Evaluation of health system decentralization and reform of the Social Security
      system in Colombia].
AB  - The aim of this study is to present the results of the reforms in the health
      sector that have taken place in Colombia since 1990. These reforms replaced the
      previous national health system and the so-called Bismarkian social security
      system. The new system has three basic characteristics: a) the public subsidies
      are decentralized in the municipalities and territorial departments; b) the
      public hospitals have been converted into state social enterprises, which has led
      them towards a management model, and c) the health and social security system
      monopoly has been abolished and a system of health subsidies has been created for
      the poorest citizens. This article systematically collects secondary information
      extracted from the most important studies evaluating the health sector reforms in
      Colombia. The present author participated in some of these studies. The reforms
      have increased financial resources, which, has led to an increase in public
      system staff and their salaries. The availability of hospitals' budgetary
      resources has increased and the social security system has become wider,
      including 20% of the poorest population who have benefited from subsidies on
      demand. Ease of access and equity in the health system have significantly
      improved. However, indicators of public health have fallen and health
      professionals are critical of a system based on mediation, which increases
      transaction costs.

PMID- 11841756
TI  - [Health services privatization: the experiences of Chile and Costa Rica].
AB  - This study questions the premises that justify the neoliberal privatization of
      financing, managing and delivering health services. It also analyses the meaning
      of privatization and its strategies. We compare privatization in Chile and Costa
      Rica and suggest that the more limited, selective and locally designed
      privatization process in Costa Rica has resulted in a more equitable, and
      efficient health system than the imported privatization model introduced in
      Chile. The Costa Rican system also produces greater patient satisfaction and at
      the same time preserves the solidarity principle.

PMID- 11841757
TI  - [Collective medical care institutions in Uruguay. Impact of the regulation].
AB  - Collective medical care institutions have been in existence for more than a
      century and have provided medical care to more than half of Uruguayans through a
      modality that integrates insurance and provision of services. In the last decade,
      these institutions have presented a persistent deficit: 52% of the beneficiaries
      are members of institutions with a deficit of more than 4%. We analyze the impact
      of the regulation of certain aspects related to the behavior of supply (market
      concentration and quotas, risk selection, price fixing) and demand (adverse
      selection and the effect of the co-payments in services utilization). The
      regulation seems not to have promoted the necessary incentives to efficiency and
      quality by the IAMC, one of the key aspects to be approached in the context of
      sectorial reform.

PMID- 11841758
TI  - [Health inequalities in Panama].
AB  - OBJECTIVES: To document socioeconomic inequalities in health and health services
      in Panama and thus create a baseline for the prospective monitoring of the impact
      of health policies on equity. METHODS: Analysis of data from the 1997 Living
      Standards Measurement Survey, the 1990 National Population Census and birth
      registration data for 1996. The relative index of inequality and concentration
      coefficient were calculated for a wide range of indicators of out-of-pocket
      health expenditure, access, utilization and quality of health services and of
      health outcomes. RESULTS: Large and statistically significant socioeconomic
      differences in many of the variables examined were detected, almost all of which
      favored the rich. The inequalities identified included qualitative factors such
      as the type of care received as well as quantitative factors such as travelling
      times and utilization rates. Some of the inequalities were concentrated among a
      small, very poor segment of the population whilst others were the result of
      gradually increasing advantage with increased levels of outcome. CONCLUSIONS: The
      results obtained provide a valuable starting point for the Panamanian government
      from which it can identify the most serious inequalities in health and health
      service provision and develop policies to eliminate or reduce them. They also
      offer a baseline to monitor changes in the magnitude of these inequalities over
      time.

PMID- 11841759
TI  - [Changes in the hiring of health personnel: the family health program in Brazil].
AB  - This article analyzes the procedures involved in the hiring of health personnel
      in the Family Program in Brazil. We examine the values, problems and relative
      outcomes of each of the processes used in hiring doctors, nurses and health
      community workers. Before analyzing hiring procedures, the author briefly
      describes the importance and role of the Family Health Program of the Brazilian
      health care system. Based on these factors, this article aims to demonstrate the
      characteristics and effects of this key program, considered a pivotal reform in
      the Brazilian health system, on the development of human resources.Finally, after
      presenting and analyzing the data available on the hiring models and the various
      salaries of physicians and nurses in several Brazilian states and municipalities,
      the author highlights the new social context in which the government, at
      different levels, flouts the labor regulations, which are their responsibility to
      enforce. This fact alone reinforces the hypothesis that a new phase of reforms
      has already begun.

PMID- 11841760
TI  - [Human resources and the health system in Brazil].
AB  - This article discusses some questions related to human resources that act on
      Brazilian health system. At the beginning, it identifies the trends on health
      human resources in the last years. Then it shows on a brief discussion the health
      system reform, pointing out changes in the health model design through the
      implementation of the Family Health Program. This program tries to reorder the
      health care model, bringing the primary health care, in order to substitute the
      traditional model, designed to the cure of diseases and centered on hospitals. It
      also points out important changes on work conditions, such as: doctors' and
      dentists' no liberal work, low salaries, consultations paid by the HMO's,
      flexibilization of work, loss of work guarantees. Finally, it identifies serious
      problems in the Family Health Program, especially those related to the
      instability of work process and decreasing of social protection of workers who
      act on this program.

PMID- 11841761
TI  - [Transparency in public sector acquisitions. The case of hospitals in the City of
      Buenos Aires].
AB  - This paper deals with corruption and the lack of transparency in public sector
      purchases as well as with the main instruments to obtain adequate results in
      purchase negotiation.Firstly, we discuss how corruption causes concern to
      national governments, international organizations, academic centers, non
      governmental organizations and society in general. The consequences of corruption
      in Argentina and other Latin American countries are highlighted, especially the
      effect of corruption on economic growth and the way it creates economic
      inefficiency and inequality.Secondly, the database created by the Subsecretary of
      Strategic Management of the Autonomous Government of the City of Buenos Aires is
      analyzed. The central purpose of this study is to evaluate the impact of the
      Administrative Reform of 1998 on the prices of 24 products acquired by 13 general
      acute care hospitals from 1998-1999. The weighted prices, the number of units
      purchased and the total number of contracts given in this period, as well as the
      products with the greatest utilization rate, are analyzed. Multivariante analysis
      was used to identify hospitals with appropriate activity and efficient budget
      administration (activity and negotiation indicators). Price development was
      analyzed using the regression technique (ordinary least squares), which
      demonstrated an 8% reduction in prices for the year 1999. The contribution of
      each hospital to this variation is presented using dummy variables. Thus, six of
      the 13 hospitals significantly contributed to the decrease in prices. Of these
      six, three hospitals also contributed to reduction in price dispersion. The
      results obtained allow us to conclude that, if public hospitals have adequate
      purchase negotiation instruments and a uniform legal framework, they can achieve
      a good level of activity. Furthermore, public hospitals can contribute to
      reductions in price and price dispersion, at the same time as improving
      efficiency in the assignation and utilization of resources.

PMID- 11841762
TI  - [Complexity index and analysis of digestive endoscopies at a university
      hospital].
AB  - BACKGROUND: In Spain neither the cost of digestive endoscopies nor the complexity
      index (CI) have been objectively estimated. Consequently, the profitability of an
      endoscopy unit cannot be evaluated. OBJECTIVES: 1: To classify endoscopies
      according to the time taken to accomplish them in order to estimate the CI and
      determine the relative value unit (RVU). 2: To evaluate the cost of each
      examination in order to determine the profitability of endoscopy as a diagnostic
      and therapeutic tool. 3: To measure unnecessary delays in examinations and to
      determine whether there are differences in the time an examination takes
      according to the endoscopist's experience and the patient's age or sex. MATERIAL
      AND METHODS: The cost per hour of an endoscopy room was estimated by dividing the
      cost per year of employees, equipment, maintenance and the hospital's general
      costs between the hours of work per year of the endoscopy team. The time taken to
      perform endoscopies was estimated and the result was used to calculate the RVI,
      the CI and the cost of 500 consecutive endoscopies. RESULTS: The annual cost
      amounted to 349,617.69 E. Staffing costs represented 65.5%, of which 56.3% were
      direct costs. Gastroscopy was taken as the RVU (cost = 27.52 E). Anoscopy was the
      simplest procedure (RVU = 0.61, cost = 15.08 E) and colonoscopy plus polypectomy
      was the most complex procedure (RVU = 4.41, cost = 74.28 E). The greater the
      experience of the member of staff performing the procedure, the less time it took
      (p < 0.01). CONCLUSION: CI was lowest for anoscopy (URV = 0.61) and highest for
      total colonoscopy plus polypectomy (URV = 4.41). Cost and exploration time
      depended on the endoscopist's experience. Staff represented the highest
      percentage of cost.

PMID- 11841763
TI  - [Value of power Doppler ultrasonography with intravenous contrast medium
      (Levograf) in the diagnosis of acute cholecystitis].
AB  - The aim of this study was to evaluate the potential capacity of color and power
      Doppler sonography with intravenous contrast medium in the diagnosis of acute
      cholecystitis. We examined 18 patients with acute cholecystitis, 5 patients with
      chronic cholecystitis and a control group of 11 patients without gallbladder
      disease. In these patients, vascularization of the gallbladder wall was evaluated
      by color and power Doppler sonography before and after intravenous administration
      of contrast medium (Levograf). Vascularization was evaluated with a 3-point scale
      (grades 0, 1 and 3) according to the intensity and localization of signs of
      color. In the diagnosis of acute cholecystitis, basal examination with power
      Doppler had a sensitivity of 38.8%. After administration of intravenous contrast
      medium, sensitivity was 100%. In conclusion, the use of sonographic contrast
      media in the diagnosis of acute cholecystitis showed a sensitivity and
      specificity of 100%. This technique represents a viable diagnostic alternative to
      other complementary or imaging studies.

PMID- 11841764
TI  - [Clinical practice guideline on the management of patients with gastroesophageal
      reflux disease (GERD)].

PMID- 11841766
TI  - [Aceroluplasminemia, a new disease caused by iron accumulation].

PMID- 11841765
TI  - [More on amoxicillin-clavulanic acid in patients with spontaneous bacterial
      peritonitis].

PMID- 11841767
TI  - [Toxic hepatitis caused by amlodipine].

PMID- 11841768
TI  - [Dietary intake of n-3 fatty acids and the risk of acute myocardial infarction: a
      case-control study].
AB  - BACKGROUND: There is some dispute about the role of fish and n-3 polyunsaturated
      fatty acids (n-3 PUFA) consumption on the prevention of coronary heart disease.
      The aim of this study was to analyze the relationship between n-3 PUFA and fish
      consumption and the risk of a first acute myocardial infarction (AMI) in a low
      risk population from Navarre (Spain). METHOD: A hospital-based case-control study
      was conducted in Pamplona (Spain). We included 171 patients (81% males, age < 80
      years) who were admitted with a first acute myocardial infarction and 171 age,
      gender and hospital-matched controls were selected. A validated semi-quantitative
      food frequency questionnaire was administered and face-to-face interviews were
      performed. Conditional logistic regression modeling was used to take into account
      potential confounders. RESULTS: Adjusted odds ratio (OR) and 95% confidence
      intervals (CI) for the second and third tertile of n-3 PUFA intake were 0.44 (95%
      CI, 0.21-0.91) and 0.47 (95% CI, 0.22-1.00), respectively. Trend test was not
      statistically significant. Adjusted OR and 95% CI for the second and third
      tertile of fish consumption were 0.40 (95% CI, 0.19-0.83) and 0.42 (95% CI, 0.19
      0.93), respectively. Additional adjusting for n-3 PUFA led to a non-significant
      association between fish consumption and AMI. CONCLUSIONS: This study reveals a
      protective effect of n-3 PUFA and fish consumption against AMI. Our results
      suggest that a threshold exists in the quantitative dose-response relationship
      between fish intake and AMI.

PMID- 11841769
TI  - [Testing a new in-office test for determination of faecal Helicobacter pylori
      antigen].
AB  - BACKGROUND: To date, the search for an in-office reliable test for Helicobacter
      pylori infection has been unsuccessful. The aim of the present study was to
      evaluate a new immunocromatographic in-office test using monoclonal antibodies to
      determine the presence of Helicobacter pylori antigen in faeces (Stick H. pyl,
      Operon S.A. Zaragoza). We compared its reliability and reproducibility to the
      currently available test (HpSA, EIA, Premier Platinum HpSA, Meridian Diagnosis
      Inc, Cincinnati, Ohio). PATIENTS AND METHOD: 71 consecutive dyspeptic patients
      were enrolled. Helicobacter pylori status was determined by rapid urease test and
      Giemsa stain of antral biopsy. Patients with a positive result in the two tests
      were considered as infected and those with a negative result in both tests were
      regarded as not infected. Faecal Helicobacter pylori antigen was tested twice by
      means of HpSA. Four consecutive determinations of Stick H. pyl were also
      performed. We calculated sensitivity, specificity and positive and negative
      predictive values of each determination. Concordance between determinations was
      estimated by the kappa statistics. RESULTS: Forty-eight of 68 patients were
      infected by Helicobacter pylori. Sensitivity, specificity and positive and
      negative predictive values were 89-96%, 60-70% 85-88% and 74-87%, respectively,
      for Stick H. pyl and 70-75%, 60-85%, 85-92% and 55-80%, respectively, for HpSA.
      Correlation coefficients were 0.82-0.93 for Stick H. pyl and 0.57 for HpSA.
      CONCLUSIONS: The new Stick H. pyl test shows excellent sensitivity and
      reproducibility for diagnosis of H. pylori infection. Its reliability appears to
      be far better than that of HpSA.

PMID- 11841770
TI  - [Pulmonary function and quality of life in relation to bronchial colonization in
      adults with bronchiectasis not caused by cystic fibrosis].
AB  - BACKGROUND: We aimed at assessing the pulmonary function and life quality of
      patients with bronchiectasis not caused by cystic fibrosis (CF) on the basis of
      the presence or absence of colonization (with Pseudomonas or other
      microorganisms). PATIENTS AND METHOD: Prospective, randomised control-case study
      of patients with bronchiectasis who came to the Pneumology area of the Hospital
      Universitario de Canarias between January 1999 and December 2000 in a stable
      clinic situation. Patients must had no antibiotic therapy over last six weeks
      before the study. Patients with CF and patients who had an acute respiratory
      disease were excluded. We obtained two sputum samples for culture with an
      interval of six weeks between both. We determined the expiratory flow in the
      first second (FEV1), the forced vital capacity (FVC) and arterial gases. Quality
      of life was measured by the St. George respiratory questionnaire. RESULTS: We
      included 70 patients, 25 males (35%) and 45 females (64%), with a mean (SD) age
      of 56 (17) years. There were 14 patients who had Pseudomonas (Ps-group), 10 who
      had other microorganisms (another-group) and 46 patients who had no microorganism
      in sputum culture (no-group). The pulmonary function of the no-group (FEV<SUB<1%:
      73 [24] and FVC%: 79 [21]) was better than that of the Ps-group (FEV1%: 47 [27];
      p = 0.00; FVC%: 61 [28]; p = 0.04). The quality of life of the no-group (total
      score (TS): 33.2 [18.9]) was better than that of the Ps-group (TS: 54 [23.2]; p =
      0.00) and that of the another-group (TS: 52.2 [20.4]; p = 0.02). CONCLUSIONS: Non
      CF patients whose bronchiectasis are colonized with Pseudomonas have worse
      pulmonary function and quality of life than uncolonized ones. Moreover, patients
      having microorganisms other than Pseudomonas have a worse quality of life than
      those without microorganisms.

PMID- 11841772
TI  - [Guillain-Barre syndrome].

PMID- 11841771
TI  - [Distribution of the serum concentration of vitamin C, folic acid and vitamin B12
      in a representative sample of the adult population of Catalonia (Spain)].
AB  - BACKGROUND: The subclinical deficiency of certain micronutrients (vitamin C,
      folic acid, vitamin B12) has been associated with disorders as cardiovascular
      diseases, cancer, cataracts, immunodepression and fetal neural tube defects. The
      purpose of this study was to determine the serum concentration of vitamin C,
      folic acid and vitamin B12 in the Catalan population and to examine the
      prevalence of deficits of these micronutrients. SUBJECTS AND METHOD: We studied a
      subsample of individuals (n = 378) from a representative sample of people aged 18
      to 75 years who had participated in the study of the Nutritional Status of the
      Catalan Population (1992-93). Serum concentrations of vitamin C, folic acid and
      vitamin B12 were determined. RESULTS: The serum concentration of vitamin C was
      lower in men than in women. 4.6 and 0.5% subjects were found to have marginal and
      severe deficits of vitamin C, respectively. 4 and 1.6% subjects had marginal and
      severe deficits of folic acid, respectively. Folic acid deficit involved up to
      12.9% women aged 18-34 years and up to 9.1% men within the same age group.
      Subjects who had a severe deficit of folic acid consumed more than 20 g/day of
      alcohol. The serum concentration of vitamin B12 was greater in women than in men.
      1.9% individuals had a marginal deficit of this vitamin. CONCLUSION: The sample
      of individuals studied were found to have a correct nutritional status with
      regard to vitamin C, folic acid and vitamin B12. This may explain the lower
      incidence of cancer and ischemic heart disease associated with the Mediterranean
      diet.

PMID- 11841773
TI  - [Preventable kidney diseases: on nephrology's return].

PMID- 11841774
TI  - [The syndrome of right bundle branch block, ST segment elevation in V1-V3 and
      sudden cardiac death].

PMID- 11841775
TI  - [Inappropriate admissions and stays in internal medicine].

PMID- 11841776
TI  - [Are really objective the criteria of Appropriateness Evaluation Protocol
      (AEP)?].

PMID- 11841778
TI  - [Human resource in the health-care system: pending reforms].

PMID- 11841780
TI  - [Fibrinogen and monocyte count during the initial phase of ischaemic ictus].

PMID- 11841781
TI  - A novel mechanism of action and potential use for lobeline as a treatment for
      psychostimulant abuse.
AB  - Lobeline, an alkaloidal constituent of Lobelia inflata LINN., has a long history
      of therapeutic usage ranging from emetic and respiratory stimulant to tobacco
      smoking cessation agent. Although classified as both an agonist and an antagonist
      at nicotinic receptors, lobeline has no structural resemblance to nicotine, and
      structure--function relationships do not suggest a common pharmacophore. Lobeline
      inhibits nicotine-evoked dopamine release and [3H]nicotine binding, thus acting
      as a potent antagonist at both alpha3beta2(*) and alpha4beta2(*) neuronal
      nicotinic receptor subtypes. However, lobeline does not release dopamine from its
      presynaptic terminal, but appears to induce the metabolism of dopamine
      intraneuronally. Reevaluation of the mechanism by which lobeline alters dopamine
      function reveals that its primary mechanism is inhibition of dopamine uptake and
      promotion of dopamine release from the storage vesicles within the presynaptic
      terminal, via an interaction with the tetrabenazine-binding site on the vesicular
      monoamine transporter (VMAT2). Thus, lobeline appears to perturb the fundamental
      mechanisms of dopamine storage and release. Based on its neurochemical mechanism,
      the ability of lobeline to functionally antagonize the neurochemical and
      behavioral effects of the psychostimulants amphetamine and methamphetamine was
      examined. Lobeline was found to inhibit the amphetamine-induced release of
      dopamine in vitro, and amphetamine-induced hyperactivity, drug discrimination,
      and self-administration. However, lobeline does not support self-administration
      in rats, suggesting a lack of addiction liability. Thus, lobeline may reduce the
      abuse liability of these psychostimulants. The development of lobeline and
      lobeline analogs with targeted selectivity at VMAT2 represents a novel class of
      therapeutic agents having good potential as efficacious treatments for
      methamphetamine abuse.

PMID- 11841782
TI  - Antimicrobial effect of resveratrol on dermatophytes and bacterial pathogens of
      the skin.
AB  - The phytoalexin resveratrol is commonly found in food and drinks, including red
      wine, grapes, and peanuts. Many studies have shown that this compound has anti
      inflammatory properties, and it has been ascribed as having health benefits that
      help to prevent cancer and coronary heart disease. A treatment that combines
      antimicrobial and anti-inflammatory actions may be desirable for alleviating many
      skin conditions that range in severity. Therefore, we evaluated the antimicrobial
      activity of resveratrol against bacteria and dermatophytes that are major
      etiologic agents of human skin infections. Using the broth microdilution protocol
      of the National Committee for Clinical Laboratory Standards (NCCLS) M7-A5, growth
      of the bacterial species Staphylococcus aureus, Enterococcus faecalis, and
      Pseudomonas aeruginosa was inhibited at 171-342 microg/mL of resveratrol in the
      solvent dimethyl sulfoxide. Using the NCCLS protocol M38-P, activity against the
      fungal species Trichophyton mentagrophytes, Trichophyton tonsurans, Trichophyton
      rubrum, Epidermophyton floccosum, and Microsporum gypseum was also tested. The
      growth of dermatophytes was inhibited at 25-50 microg/mL of resveratrol. Thus,
      this study indicates a novel application for resveratrol, a molecule of plant
      defense, to combat human fungal pathogens. Resveratrol and its analogs may have
      wide application to skin conditions that afflict a significant portion of our
      population, and may also have promising clinical potentials in diabetic wounds.

PMID- 11841783
TI  - Multiple mechanisms of resistance to methotrexate and novel antifolates in human
      CCRF-CEM leukemia cells and their implications for folate homeostasis.
AB  - We determined the mechanisms of resistance of human CCRF-CEM leukemia cells to
      methotrexate (MTX) vs. those to six novel antifolates: the polyglutamatable
      thymidylate synthase (TS) inhibitors ZD1694, multitargeted antifolate,
      pemetrexed, ALIMTA (MTA) and GW1843U89, the non-polyglutamatable inhibitors of
      TS, ZD9331, and dihydrofolate reductase, PT523, as well as DDATHF, a
      polyglutamatable glycinamide ribonucleotide transformylase inhibitor. CEM cells
      were made resistant to these drugs by clinically relevant intermittent 24 hr
      exposures to 5-10 microM of MTX, ZD1694, GW1843U89, MTA and DDATHF, by
      intermittent 72 hr exposures to 5 microM of ZD9331 and by continuous exposure to
      stepwise increasing concentrations of ZD9331, GW1843U89 and PT523. Development of
      resistance required only 3 cycles of intermittent drug exposure to ZD1694 and
      MTA, but 5 cycles for MTX, DDATHF and GW1843U89 and 8 cycles for ZD9331. The
      predominant mechanism of resistance to ZD1694, MTA, MTX and DDATHF was impaired
      polyglutamylation due to approximately 10-fold decreased folylpolyglutamate
      synthetase activity. Resistance to intermittent exposures to GW1843U89 and ZD9331
      was associated with a 2-fold decreased transport via the reduced folate carrier
      (RFC). The CEM cell lines resistant to intermittent exposures to MTX, ZD1694,
      MTA, DDATHF, GW1843U89 and ZD9331 displayed a depletion (up to 4-fold) of total
      intracellular reduced folate pools. Resistance to continuous exposure to ZD9331
      was caused by a 14-fold increase in TS activity. CEM/GW70, selected by continuous
      exposure to GW1843U89 was 50-fold resistant to GW1843U89, whereas continuous
      exposure to PT523 generated CEM/PT523 cells that were highly resistant (1550
      fold) to PT523. Both CEM/GW70 and CEM/PT523 displayed cross-resistance to several
      antifolates that depend on the RFC for cellular uptake, including MTX (95- and
      530-fold). CEM/GW70 cells were characterized by a 12-fold decreased transport of
      [3H]MTX. Interestingly, however, CEM/GW70 cells displayed an enhanced transport
      of folic acid, consistent with the expression of a structurally altered RFC
      resulting in a 2.6-fold increase of intracellular folate pools. CEM/PT523 cells
      displayed a markedly impaired (100-fold) transport of [3H]MTX along with 12-fold
      decreased total folate pools. In conclusion, multifunctional mechanisms of
      resistance in CEM cells have a differential impact on cellular folate
      homeostasis: decreased polyglutamylation and transport defects lead to folate
      depletion, whereas a structurally altered RFC protein can provoke expanded
      intracellular folate pools.

PMID- 11841784
TI  - Pathways for alpha-D-ribose utilization for nucleobase salvage and 5-fluorouracil
      activation in rat brain.
AB  - Recently, interest has increased in the use of alpha-D-ribose (Rib) as a
      naturally occurring nutriceutical for enhancement of cardiac and muscular
      performance. Most likely the elevation of available PRPP, following Rib
      administration, plays a key role in the salvage of purine nucleobases, thus,
      accelerating the restitution of ATP pool. In addition, administration of Rib
      improves some of the neurological symptoms in patients with adenylosuccinase
      deficiency. In this paper, we show that rat brain extract can catalyze the Rib
      mediated salvage of both adenine and uracil, as well as the activation of the
      pyrimidine pro-drug, 5-fluorouracil (5-FU). The results strongly support that the
      pentose may be converted to both PRPP and Rib1-P for the salvage of the adenine
      and uracil, respectively. Most likely two-reaction pathway, composed of
      ribokinase and PRPP synthetase, is responsible of the PRPP formation, needed to
      salvage adenine to adenine nucleotides. A two-reaction pathway, composed of
      ribokinase and phosphopentomutase, appears to be responsible of the Rib1-P
      formation, needed to salvage uracil to uracil-nucleotides and to activate 5-FU to
      cytotoxic 5-FU-ribonucleotides. alpha-D-2'-Deoxyribose (deoxyRib) has a
      negligible effect on both the salvage of natural nucleobases to
      deoxyribonucleotides and on the activation of 5-FU to cytotoxic 5-FU
      deoxynucleotides.

PMID- 11841785
TI  - Influence of t-butylhydroquinone and beta-naphthoflavone on formation and
      transport of 4-methylumbelliferone glucuronide in Caco-2/TC-7 cell monolayers.
AB  - Human Caco-2 cells have been established as a model system for intestinal
      biotransformation and permeability. When grown on Transwell polycarbonate filters
      they develop morphologic and biochemical characteristics of enterocytes with well
      separated apical and basolateral surfaces. In addition, Caco-2/TC-7 cells have
      proven to be useful to study regulation of human UDP-glucuronosyltransferases
      (UGTs) by Ah receptor agonists and antioxidant-type inducers such as beta
      naphthoflavone (BNF) and t-butylhydroquinone (TBHQ). In the present
      investigation, formation and transport of 4-methylumbelliferone glucuronide was
      studied in intact Caco-2 cell monolayers. The following results were obtained:
      when loaded with 50-200 microM MUF either apically or basolaterally, MUF-GA was
      the major metabolite which was mostly released (80%) at the basolateral surface,
      probably via the multidrug resistance protein isoform MRP3; MUF sulfate formation
      was low (5 +/-2%). Pretreatment of cells with 80 microM TBHQ or 50 microM BNF for
      72 hr before addition of 100 microM MUF enhanced basolateral secretion of MUF-GA
      1.4- and 1.7-fold, respectively. However, at >200 microM MUF, MUF-GA secretion
      and induction was smaller, probably due to inhibition of intracellular UGT
      activity. MRP3 protein was localized to the basolateral surface of Caco-2 cells
      but was not induced by TBHQ or BNF. The results suggest that MUF-GA is mostly
      secreted basolaterally in Caco-2 cell monolayers. Treatment with TBHQ or BNF
      significantly enhanced MUF-GA formation in the intact cell.

PMID- 11841786
TI  - Interaction of specifically chemically modified dextrans with transforming growth
      factor beta1: potentiation of its biological activity.
AB  - Transforming growth factor beta (TGFbeta), a potent multifunctional cytokine, is
      well known to demonstrate heparin binding ability. This study investigated the
      binding capacity of heparin-like family of chemically modified dextrans to
      TGFbeta1. Dextran derivatives with various substitution contents in
      carboxymethyl, benzylamide and sulfate groups were evaluated using a gel mobility
      shift assay. This structure-function study indicated that a synergistic role of
      benzylamide and sulfate substituents resulted in an optimal interaction with the
      growth factor. The effect of these polymers on the biological response of
      TGFbeta1 was assessed using mink lung epithelial cells transfected with a
      plasminogen activator inhibitor-1 promoter-luciferase construct (PAI/Luc). When
      the growth factor was mixed with 250 microg/mL of carboxymethyl-benzylamide
      dextran (DCMB) or carboxymethyl-benzylamide-sulfate-dextran (DCMBSu), the
      luciferase gene expression was enhanced. Only polymers exhibiting TGFbeta1
      binding demonstrated a biological potentiating effect. However, this effect was
      strongly amplified as the cell plating time increased (35-fold increase with a 2
      days plating time versus 1.1-fold increase with a 4 hr plating time at a 0.25
      ng/mL concentration of TGFbeta1). TGFbeta1 induced the PAI/Luc construct in a
      dose-dependent fashion but its effect diminished when added to cells previously
      cultured for 24 and 48 hr. The results indicated that the potentiating effect
      required a complex formation between TGFbeta1 and polymers, the action of which
      seeming to locally maintain TGFbeta1 in an active form. TGFbeta isoforms playing
      a key role in the process of bone repair, specifically designed functionalized
      dextrans could potentiate the in vivo TGFbeta1 biological effect and be used in
      the field of wound healing applications.

PMID- 11841787
TI  - Activation of transcription factors by drugs inducing oxidative stress in rat
      liver.
AB  - Chemically induced oxidative stress of the liver associates with gene
      reprogramming and activation of some transcription factors (TFs), in particular
      nuclear factor-kappaB (NF-kappaB). We have now investigated other TFs, such as
      activator protein-1 (AP-1) and hypoxia inducible factor-1 (HIF-1) that we had
      shown to be activated in rat liver during heat shock, ischemia or post-ischemic
      reperfusion, and signal transducer and activator of transcription (STAT),
      CCAAT/enhancer binding protein (C/EBP) and hepatocyte nuclear factor-1 (HNF-1),
      which may be involved in the response of the liver to injury. The expression of
      target genes, containing consensus sequences for these TFs was assessed by
      Northern and Western blot analysis. The rats were treated with buthionine
      sulfoximine, nitrofurantoin (NF) or phorone (Ph), which cause liver oxidative
      stress with different mechanisms. All these agents activated AP-1, known to
      depend on redox state, HIF-1, initially described as an hypoxia-responsive TF,
      and STAT3, generally connected to the response to cytokines. HNF-1 a constitutive
      TF associated with liver-specific gene expression was not affected. The
      composition of AP-1 was slightly different according to the drug used for
      treatment. The levels of the mRNAs for heme oxygenase-1 (HO-1), Aldolase A and
      alpha(1)-acid glycoprotein as well as the corresponding proteins increased after
      the treatments, thus, indicating that the activation of the TFs was functional.
      These observations suggest that the treatment of rats with drugs inducing
      oxidative stress causes a broad spectrum of changes in gene expression with
      features common to stresses generally considered as separate entities.

PMID- 11841788
TI  - Inhibitory effect of adrenomedullin on basal and tumour necrosis factor alpha
      stimulated endothelin-1 synthesis in bovine aortic endothelial cells is
      independent of cyclic AMP.
AB  - Adrenomedullin (ADM) is a potent vasodilator and reverses the vasoconstrictor
      action of endothelin-1 (ET-1). These studies aimed to determine the effect of ADM
      on ET-1 synthesis in bovine aortic endothelial cells (BAEC) and to identify the
      possible mechanisms involved. In this cell model, ADM increased cyclic AMP
      production by BAEC with threshold concentrations of 100 pM and an EC(50) of 1 nM.
      This effect was not blocked by co-treatment with the CGRP type 1 receptor
      antagonist CGRP(8--37). ADM caused a potent concentration-dependent inhibition of
      ET-1 release that was correlated with reduced preproET-1 mRNA levels. This
      reached a maximal reduction of 70% compared to basal levels after 2 and 6 hr
      exposure of BAEC to 1 nM ADM, with significant decreases at concentrations as low
      as 10 pM. However, a 100-fold discrepancy between the threshold ADM concentration
      for cyclic AMP production and inhibition of ET-1 release was observed. Treatment
      of BAEC with tumour necrosis factor alpha (TNFalpha; 10 ng/mL) caused a 2-fold
      increase over basal ET-1 release. ADM caused a more marked reduction in
      stimulated ET-1 synthesis with a threshold of 1 pM, and suppression of ET-1
      release to basal levels at 100 nM. 8-Bromo cyclic AMP, showed no concentration
      dependent inhibition of ET-1 release, yet caused a 50% reduction in TNFalpha
      stimulated intercellular adhesion molecule-1 (ICAM-1) mRNA levels. Thus,
      physiological ADM concentrations inhibit ET-1 synthesis independently of cyclic
      AMP in BAEC at the level of preproET-1 mRNA expression. The high sensitivity of
      this inhibition implicates ADM as an important physiological regulator of
      endothelial ET-1 production.

PMID- 11841789
TI  - Binding thermodynamics at the human A(3) adenosine receptor.
AB  - The thermodynamic parameters DeltaG , DeltaH and DeltaS of the binding
      equilibrium of six adenosine receptor agonists and five antagonists at adenosine
      A(3) receptors were determined by means of affinity measurements at six different
      temperatures (4, 10, 15, 20, 25 and 30) and van't Hoff plots were constructed.
      Affinity constants were measured on Chinese hamster ovary (CHO) cells transfected
      with the human A(3) receptors by inhibition assays of the binding of the
      selective A(3) antagonist [3H]MRE 3008F20. van't Hoff plots were linear for
      agonists and antagonists in the temperature range 4-30 degree. Their
      thermodynamic parameters fall in the ranges 21 < or = DeltaH < or = 67kJmol(-1)
      and 208 < or = DeltaS < or =410 J(Kmol)(-1) for agonists and -52 < or = DeltaH <
      or = -9 kJmol(-1) and 16 < or = DeltaS < or =81 J(K/mol)(-1) for antagonists,
      showing that agonist binding is always totally entropy-driven while antagonist
      binding is enthalpy- and entropy-driven. The results are discussed with the aim
      of obtaining new details on the nature of the forces driving the A(3) binding at
      a molecular level.

PMID- 11841790
TI  - Role of redox status on the activation of mitogen-activated protein kinase
      cascades by NSAIDs.
AB  - High concentrations of non steroidal antiinflammatory drugs (NSAIDs) exert
      preventive effects against carcinogenesis. Their molecular mechanism of action
      remains to be elucidated. Based on previous reports with salicylate, we have made
      the hypothesis that various NSAIDs can activate the mitogen-activated protein
      kinases (MAPK). Moreover, we tested the idea that NSAIDs act by increasing the
      effects of oxidative stress. We report that in human colorectal carcinoma cells
      NSAIDs stimulated the three families of MAPK, extracellular regulated kinases, c
      Jun N-terminal kinases, p38 MAPK and that this stimulation is prevented by N
      acetyl cysteine. In cultured astrocytes, a biological system less sensitive to
      oxidative stress, we show that a short treatment by NSAIDs strongly activated the
      three MAP kinases in the presence of H(2)O(2). A 25 microM H(2)O(2), unable to
      stimulate by itself the MAP kinases, promote an almost complete activation of MAP
      kinases in the presence of NSAIDs. The activation of MAP kinases by H(2)O(2) and
      NSAIDs was suppressed by quinone reductase inhibitors, suggesting that "redox
      cycling" was involved in the activation mechanisms of MAP kinases by H(2)O(2) and
      NSAIDs. The mobility on SDS-PAGE of the apoptosis signal-regulating kinase, which
      activates C-Jun N-terminal kinases and p38 MAPK cascades, was reduced by H(2)O(2)
      and NSAIDs, suggesting, that H(2)O(2) and NSAIDs activated apoptosis signal
      regulating kinase by increasing its state of phosphorylation. In conclusion, we
      demonstrate that various NSAIDs can activate the three families of MAP kinases
      and that this activation depends on the presence of reactive oxygenated species.
      These results give a new insight into the mechanism of the action of NSAIDs.

PMID- 11841791
TI  - Sensitivity of HaCat keratinocytes to diabetogenic toxins.
AB  - Metabolic, genetic and environmental factors very likely play an important role
      in the development of skin lesions in diabetes mellitus. While these lesions are
      involved in secondary diabetes complications, various diabetogenic genotoxic
      agents may induce direct skin damage. In the present study we examined the
      potential of known diabetogenic agents (streptozotocin (STZ) and alloxan (AL)),
      with different mechanisms of action, for induction of direct injury in an
      immortal human keratinocyte HaCat cell line. In contrast to STZ, which induces
      alkylation of DNA, a genotoxic effect of AL is achieved through reactive oxygen
      species. We found that HaCat cells are highly sensitive to STZ, but not to AL. At
      a concentration of 10mM STZ, cell viability decreased to 32 +/-13% of control
      (P<0.05), as compared to 82 +/-14% with 10mM of AL. Cells treated with 10 and
      20mM STZ showed a significant increase in apoptosis (3.9- and 6.7-fold), but not
      in necrosis, compared to naive cells (P<0.05). In contrast to STZ, no increase in
      apoptotic and necrotic cell death was observed after AL treatment. Pretreatment
      with non-metabolizable 3-O-methyl glucose (3-OMG), which can blockade glucose
      transporter, or with poly(ADP-ribose) polymerase inhibitors (nicotinamide or 3
      aminobenzamide), did not protect keratinocytes from STZ injury. Our results show
      that STZ, but not AL, is highly toxic to the HaCat cell line. Unlike insulin
      producing cells, STZ-induced injury of immortal human keratinocyte HaCat cells is
      independent of the glucose transporters as well as of the activation of poly(ADP
      ribose) polymerase.

PMID- 11841793
TI  - The polymorphic human glutathione transferase T1-1, the most efficient
      glutathione transferase in the denitrosation and inactivation of the anticancer
      drug 1,3-bis(2-chloroethyl)-1-nitrosourea.
AB  - A member of the Theta class of human glutathione transferases (GST T1-1) was
      found to display the greatest catalytic activity towards the cytostatic drug 1,3
      bis(2-chloroethyl)-1-nitrosourea (BCNU) of the GSTs studied. In this
      investigation (the most extensive to date), enzymes from four classes of the
      soluble human GSTs were heterologously expressed, purified, and kinetically
      characterized. From the 12 enzymes examined, only GST M2-2, GST M3-3 and GST T1-1
      had significant activities with BCNU. This establishes that the activity is not a
      characteristic of a particular class of GSTs. Although GST M3-3 was previously
      reported to have the greatest activity with BCNU, the current investigation
      demonstrates that GST M2-2 is equally active and that GST T1-1 has an
      approximately 20-fold higher specific activity than either of the Mu class
      enzymes. A more rigorous kinetic analysis of GST T1-1 gave the following
      parameters with BCNU: a k(cat) of 0.035 +/-0.003s(-1) and a K(M) of 1.0 +/-
      0.1mM. The finding that GST T1-1 has the highest activity towards BCNU is
      significant since GST T1-1 is expressed in the brain, a common target for BCNU
      treatment. Furthermore, the existence of a GST T1-1 null allele in up to 60% in
      some populations, may influence both the sensitivity of tumors to chemotherapy
      and the severity of adverse side-effects in patients treated with this agent.

PMID- 11841792
TI  - Matrix and serine protease expression during leukemic cell differentiation
      induced by aclacinomycin and all-trans-retinoic acid.
AB  - In myeloid leukemia, immature leukemic cells are able to egress into peripheral
      blood to infiltrate extra-medullary organs. We therefore analyzed the migrating
      and invasive potential of human HL-60 and NB4 cell lines, representative of acute
      myelogenous leukemia, their ability to express matrix metalloproteases (MMPs),
      tissue inhibitors of metalloproteases (TIMPs) and urokinase plasminogen activator
      (uPA) in response to differentiating agents. Granulocytic differentiation by all
      trans-retinoic acid (ATRA) and aclacinomycin (ACLA) strongly increased HL-60 and
      NB4 cell migration and invasion. At mRNA and protein levels, these cell lines
      produced significant amounts of MMP-9 (HL-60<NB4). Granulocytic differentiation
      by ACLA increased both pro and active forms of MMP-9 whereas ATRA decreased them
      and stimulated uPA mRNAs. TIMP-1, the physiological MMP inhibitor, increased
      during granulocytic differentiation whereas TIMP-2 did not significantly vary.
      Use of Batimastat and aprotinin suggests that ATRA was active by modulating the
      uPA system while ACLA interfered with MMP expression. In conclusion, our data
      demonstrate that HL-60 and NB4 cells express MMPs and uPA which are
      differentially regulated by the differentiating agents ATRA and ACLA and suggest
      the clinical usefulness of MMPs and serine protease inhibitors in the prophylaxis
      and treatment of the ATRA syndrome.

PMID- 11841794
TI  - Inhibitory effect of the plant-extract osthole on L-type calcium current in NG108
      15 neuronal cells.
AB  - The effects of osthole, a coumarin isolated from Cnidium monnieri (L.) Cusson, on
      ionic currents in a mouse neuroblastoma and rat glioma hybrid cell line, NG105
      18, were investigated with the aid of the whole-cell voltage-clamp technique.
      Osthole (0.3-100 microM) caused an inhibition of voltage-dependent L-type Ca(2+)
      current (I(Ca,L)) in a concentration-dependent manner. Osthole produced no change
      in the overall shape of the current-voltage relationship of I(Ca,L). The IC(50)
      value of the osthole-induced inhibition of I(Ca,L) was 4 microM. The presence of
      osthole (3 microM) shifted the steady state inactivation curve of I(Ca,L) to a
      more negative potential by approximately -15mV. Osthole (3 microM) also produced
      a prolongation in the recovery of I(Ca,L) inactivation. Although osthole might
      suppress phosophodiesterases to increase intracellular adenosine-3',5'-cyclic
      monophosphate (cyclic AMP) or guanosine-3',5'-cyclic monophosphate (cyclic GMP),
      sp-cAMPS did not affect I(Ca,L) and 8-bromo-cyclic GMP slightly suppressed it.
      Thus, osthole-mediated inhibition of I(Ca,L) was not associated with
      intracellular cyclic AMP or GMP. However, no effect of osthole on voltage
      dependent K(+) outward current was observed. Under a current-clamp mode, osthole
      could decrease the firing frequency of action potentials. Therefore, the channel
      blocking properties of osthole may, at least in part, contribute to the
      underlying mechanisms by which it affects neuronal or neuroendocrine function.

PMID- 11841795
TI  - Influence of isomerisation on the growth inhibitory effects and cellular activity
      of 13-cis and all-trans retinoic acid in neuroblastoma cells.
AB  - Treatment with 13-cis retinoic acid (13-cis RA) has been shown to significantly
      improve the clinical outcome of children with high-risk neuroblastoma. Despite
      the large number of studies investigating the cellular effects of retinoids in
      neuroblastoma cells, the influence of RA isomerisation and the factors that
      determine the extent of RA isomerisation and uptake are unknown. The aim of this
      study was to establish the extent of extra- and intracellular isomerisation of 13
      cis RA and all-trans retinoic acid (ATRA) in neuroblastoma cell lines, and to
      investigate the influence of isomerisation on their growth inhibitory effects and
      on the regulation of expression of cellular retinoic acid binding protein II
      (CRABP II) and RAR-beta. Limited extracellular isomerisation was observed up to
      72 hr after incubation of four neuroblastoma cell lines with 10 microM 13-cis RA
      or ATRA. The retinoic acid isomer present initially in the medium accounted for
      >75% of extracellular retinoid exposure. By contrast, incubation with 13-cis RA
      resulted in intracellular levels of ATRA comparable to those of 13-cis RA. This
      degree of intracellular isomerisation was not observed after ATRA incubations,
      with 13-cis RA accounting for <10% of total intracellular retinoids. No
      differences were observed in the sensitivity of three N-type neuroblastoma cell
      lines to either 13-cis RA (IC(50): 11.2-13.9 microM) or ATRA (IC(50): 12.9-14.4
      microM), despite 10-fold differences in intracellular retinoid levels. A decrease
      in sensitivity to 13-cis RA (IC(50)=137 microM), as compared to ATRA (IC(50)=41
      microM), was observed in the S-type cell line SH S EP. RAR-beta was induced in a
      dose-dependent manner in SH SY 5Y cells following incubation with ATRA, whereas a
      weaker and delayed induction was observed with 13-cis RA. Similarly, incubation
      with ATRA resulted in a greater induction of CRABP II in these cells. In summary,
      these results indicate either an intracellular conversion of 13-cis RA to ATRA or
      a selective uptake of ATRA and suggest that this may mediate the differential
      activity of 13-cis RA in neuroblastoma cell subtypes.

PMID- 11841796
TI  - Structure-activity studies of bufokinin, substance P and their C-terminal
      fragments at bufokinin receptors in the small intestine of the cane toad, Bufo
      marinus.
AB  - Bufokinin is a substance P-related tachykinin peptide with potent spasmogenic
      actions, isolated from the intestine of the cane toad, Bufo marinus. Bufokinin
      acts via a tachykinin receptor with similarities to the mammalian NK(1) receptor.
      In this structure-activity study of bufokinin, substance P (SP) and their C
      terminal fragments, we have used isolated segments and homogenates of toad small
      intestine to compare the contractile potencies and abilities to compete for the
      binding of [125I]-Bolton-Hunter bufokinin. In general, potency was very similar
      in both studies (r=0.956) and was primarily related to peptide length, with the
      natural undecapeptide tachykinins bufokinin - ranakinin>SP- cod SP -trout SP
      being most potent. The weakest peptides were [Pro(9)]SP, BUF(7-11) and SP(7-11).
      Bufokinin fragments (BUF) were approximately equipotent to the corresponding SP
      fragments, with only BUF(5-11) showing unexpectedly low binding affinity. Data
      obtained with SP, bufokinin and fragments were subjected to quantitative
      structure--activity (QSAR) analysis which demonstrated that molecular
      connectivity and shape descriptors yielded significant regression equations (r
      approximately 0.90). The predictive capacity of the equations was confirmed using
      ranakinin, trout SP and cod SP, but not using the synthetic analogs [Pro(9)]SP
      and [Sar(9)]SP. The study suggests that the full undecapeptide sequence of
      bufokinin is required for optimal activity, with high potency conferred by
      Lys(1), Pro(2), Gly(9) and probably Tyr(8). The finding that receptor-ligand
      interactions were correlated with the shape descriptor 2kappa(alpha) and favored
      by basic and rigid residues at position 1-3 is consistent with an important role
      of conformation at the N-terminus of bufokinin.

PMID- 11841797
TI  - Wogonin and fisetin induce apoptosis in human promyeloleukemic cells, accompanied
      by a decrease of reactive oxygen species, and activation of caspase 3 and Ca(2+)
      dependent endonuclease.
AB  - Seven structurally related flavonoids including luteolin, nobiletin, wogonin,
      baicalein, apigenin, myricetin and fisetin were used to study their biological
      activities on the human leukemia cell line, HL-60. On MTT assay, wogonin,
      baicalein, apigenin, myricetin and fisetin showed obvious cytotoxic effects on HL
      60 cells, with wogonin and fisetin being the most-potent apoptotic inducers among
      them. The cytotoxic effects of wogonin and fisetin were accompanied by the dose-
      and time-dependent appearance of characteristics of apoptosis including DNA
      fragmentation, apoptotic bodies and the sub-G1 ratio. Treatment with an apoptosis
      inducing concentration of wogonin or fisetin causes rapid and transient induction
      of caspase 3/CPP32 activity, but not caspase 1 activity. Further, cleavage of
      poly(ADP-ribose) polymerase (PARP) and decrease of pro-caspase 3 protein were
      detected in wogonin- and fisetin-treated HL-60 cells. An increase in the pro
      apoptotic protein, bax, and a decrease in the anti-apoptotic protein, Mcl-1, were
      detected in fisetin- and wogonin-treated HL-60 cells. However, Bcl-2, Bcl-XL, and
      Bad all remained unchanged in wogonin- and fisetin-treated HL-60 cells. In vitro
      chromatin digestion revealed that endonuclease activity was profoundly enhanced
      in wogonin- and fisetin-treated HL-60 cells, and the addition of
      ethylenediaminetetraacetic acid (EDTA) or ethyleneglycoltetraacetic acid (EGTA)
      into the reaction blocked endonuclease activation and at an optimum pH of 7.5.
      The caspase 3 inhibitor, Ac-DEVD-CHO, but not the caspase 1 inhibitor, Ac-YVAD
      CHO, attenuated wogonin- and fisetin-induced DNA ladders, PARP cleavage, and
      endonuclease activation. Pretreatment of HL-60 cells with N-acetyl-cysteine or
      catalase efficiently inhibited H(2)O(2) (200 microM)-induced apoptosis, but
      showed no inhibitory effect on wogonin- and fisetin-induced DNA ladders, caspase
      3 activation, or bax protein induction. Decrease in endogenous ROS production was
      detected in wogonin- and fisetin-treated HL-60 cells by DCHF-DA assay. In
      conclusion, our experiments indicate that a decrease in intracellular peroxide
      level was involved in wogonin- and fisetin-induced apoptosis; activation of
      caspase 3 and endonuclease, induction of bax protein and suppression of Mcl-1
      protein were detected in the process.

PMID- 11841798
TI  - Clofibric acid down-regulation of metallothionein IIA in HepG2 human hepatoma
      cells.
AB  - Among the different hypotheses advanced to explain the peroxisome proliferator
      (PP)-induced hepatocarcinogenicity in rodents, one is based on the development of
      an oxidative stress due to an imbalance in the production of reactive oxygen
      species that leads to DNA damages and lipid peroxidation. On the other hand,
      human cells appear to be nonresponsive to PPs. As metallothionein proteins play
      an important antioxidant role, the aim of the present study was to investigate
      the expression of metallothionein IA (MTIA) and IIA (MTIIA) in HepG2 human
      hepatoma cells exposed to clofibric acid. When HepG2 cells were treated for 24 hr
      with 0.50 or 0.75 mM CA, a significant decrease was observed in MT protein-level
      determined by Western blotting and in the MTIIA mRNA content analyzed by RT-PCR
      and Northern blotting. No significant change was observed in the MTIA mRNA amount
      whatever the CA concentration and the duration of treatment. The decrease in
      MTIIA mRNA-level was not mediated via peroxisome proliferator-activated receptor
      alpha as attested by our data from gel mobility shift DNA binding assays, Dot
      blotting and cotransfection experiments with MTIIA promoter-driven luciferase
      reporter gene and PPARalpha expression vector. These results provide new insights
      about the pleiotropic effects of PPs on human cells.

PMID- 11841799
TI  - The effect of methylglyoxal-bis(guanylhydrazone) on mitochondrial Ca(2+) fluxes.
AB  - Methylglyoxal-bis(guanylhydrazone) (MGBG) induces a dose-dependent inhibition of
      the electrophoretic Ca(2+) uptake by rat liver mitochondria (RLM) without
      affecting the electrical membrane potential. MGBG is also able to inhibit the
      electroneutral Ca(2+) release from mitochondria. These effects result in a
      progressive increase of Ca(2+) level in suspending medium indicating that Ca(2+)
      uptake is inhibited at higher extent than Ca(2+) efflux. Spermine instead,
      induces a lowering of external Ca(2+) concentration. This action is reversed by
      MGBG which again raises the external Ca(2+) concentration then in the absence of
      spermine, though at a lower extent. The mechanism of MGBG effects and their
      implications on energy metabolism are discussed.

PMID- 11841800
TI  - Inhibition of nucleotide excision repair and sensitisation of cells to DNA cross
      linking anticancer drugs by F 11782, a novel fluorinated epipodophylloid.
AB  - F 11782, or 2',3'-bis-pentafluorophenoxyacetyl-4',6'-ethylidene-beta-D-glucoside
      of 4'-phosphate-4'-dimethylepipodophyllotoxin 2-N-methyl glucamine salt, a novel
      dual catalytic inhibitor of topoisomerases I and II, was identified as a potent
      inhibitor of nucleotide excision repair (NER) by screening procedures using the
      in vitro 3D (DNA damage detection) assay. F 11782 was then shown predominantly to
      inhibit the incision rather than the repair synthesis step, using two new
      methodologies derived from this 3D assay, effectively ruling out any inhibition
      of polymerases delta/var epsilon. Moreover, data from two other in vitro assays
      showed an absence of any effect of F 11782 on: (i) the DNA damage binding of the
      XPA-RPA complex, and (ii) on SV40 large T-antigen helicase activity. Therefore,
      the inhibitory activity of F 11782 on NER may involve an inhibition of the ERCC1
      XPF or XPG endonuclease activity. Moreover, inhibition of DNA repair by F 11782
      was confirmed in human A549 cells by monitoring unscheduled DNA synthesis
      following mechlorethamine treatment. Such an inhibition provides an explanation
      for the highly synergistic cytotoxicity observed against cultured A549 lung
      tumour cells, when F 11782 was combined with cross-linking agents, such as
      cisplatin or mitomycin C. These results emphasise the unique mode of action of
      this novel molecule in inhibiting NER and provide a basis for its evaluation in
      clinical trials in combination with DNA cross-linking agents.

PMID- 11841801
TI  - Reduced DNA ligase activity in etoposide resistant human lymphatic leukaemia CEM
      cells.
AB  - Drug resistance is an obstacle preventing success of cancer chemotherapy.
      Resistance of vaccinia virus towards the topoisomerase II (topo II) targeting
      anti-cancer drug etoposide has been mapped to the viral DNA ligase gene. The
      present study was performed to elucidate if the DNA ligase activity, besides topo
      II levels, was altered in human lymphatic leukaemia cell strains with different
      levels of etoposide resistance. At measurements of DNA ligase activity with
      specific substrates, to distinguish between different DNA ligases, a reduced DNA
      ligase activity was observed in the resistant substrains. In contrast, the
      initial step of the ligation process, formation of DNA ligase--AMP complex, did
      not decrease in the resistant cell strains, suggesting an alteration in a later
      reaction leading to a deteriorated DNA ligation. The results suggest that
      decreased DNA ligase activity, besides topo II alterations, may contribute to
      etoposide resistance of the investigated CEM cells. The relevance of this finding
      will be further investigated.

PMID- 11841802
TI  - 5-Fluoroindole-3-acetic acid: a prodrug activated by a peroxidase with potential
      for use in targeted cancer therapy.
AB  - Indole-3-acetic acid and some derivatives are oxidized by horseradish peroxidase,
      forming a radical-cation that rapidly fragments (eliminating CO(2)) to form
      cytotoxic products. No toxicity is seen when either indole-3-acetic acid or
      horseradish peroxidase is incubated alone at concentrations that together form
      potent cytotoxins. Unexpectedly, 5-fluoroindole-3-acetic acid, which is oxidized
      by horseradish peroxidase compound I 10-fold more slowly than indole-3-acetic
      acid, is much more cytotoxic towards V79 hamster fibroblasts in the presence of
      peroxidase than the unsubstituted indole. The fluorinated prodrug/peroxidase
      combination also shows potent cytotoxic activity in human and rodent tumor cell
      lines. Cytotoxicity is thought to arise in part from the formation of 3-methylene
      2-oxindole (or analogues) that can conjugate with thiols and probably DNA or
      other biological nucleophiles. Levels of the fluorinated prodrug in the murine
      carcinoma NT after intraperitoneal administration of 50 mg/kg were about 200
      microM. Although these were 4-5-fold lower than plasma levels (which reached
      1mM), the integrated area under the concentration/time curve in tumors over 2 hr
      was approximately 20 mM min, almost double the exposure needed to achieve
      approximately 90-99% cell kill in human MCF7 breast or HT29 colon tumor cell
      lines and CaNT murine cells in vitro, although the human bladder T24 carcinoma
      cell line was more resistant. The high cytotoxicity of 5-fluoroindole-3-acetic
      acid after oxidative activation suggests its further evaluation as a prodrug for
      targeted cancer therapy involving antibody-, polymer-, or gene-directed delivery
      of horseradish peroxidase or similar activating enzymes.

PMID- 11841804
TI  - Role of mitochondria in Ca(2+) oscillations and shape of Ca(2+) signals in
      pancreatic acinar cells.
AB  - We studied the role of mitochondria in Ca(2+) signals in fura-2 loaded exocrine
      pancreatic acinar cells. Mitochondrial depolarization in response to
      carbonylcyanide-p-tryfluoromethoxyphenyl hydrazone or rotenone (assessed by
      confocal microscopy using rhodamine-123) induced a partial but statistically
      significant reduction in the decay of Ca(2+) signals under different experimental
      conditions. Spreading of Ca(2+) waves evoked by the pancreatic secretagogue
      cholecystokinin cholecystokinin octapeptide was accelerated by mitochondrial
      inhibitors, whereas the cytosolic Ca(2+) concentration ([Ca(2+)](i)) oscillations
      in response to physiological levels of this hormone were suppressed by rotenone
      and carbonylcyanide-p-tryfluoromethoxyphenyl hydrazone. Oligomycin, an inhibitor
      of mitochondrial ATP synthase, did no affect either propagation of calcium waves
      nor [Ca(2+)](i) oscillations. Individual mitochondria of rhod-2 loaded acinar
      cells showed heterogeneous matrix Ca(2+) concentration increases in response to
      oscillatory and maximal levels of cholecystokinin octapeptide. On the other hand,
      using Ba(2+) for unequivocal study of capacitative calcium entry we found that
      mitochondrial inhibitors did not affect this process. Our results show that
      although the role of mitochondria as a Ca(2+) clearing system in exocrine cells
      is quantitatively secondary, they play an essential role in the spatial
      propagation of Ca(2+) waves and in the development of [Ca(2+)](i) oscillations.

PMID- 11841803
TI  - The signalling pathway for BCG-induced interleukin-6 production in human bladder
      cancer cells.
AB  - Intravesical bacillus Calmette-Guerin (BCG) is currently the therapy of choice
      for superficial bladder cancer with a 60-70% response rate. Induction of cytokine
      production (e.g. IL-6, etc.) by BCG has been found in patient's urine in vivo as
      well as bladder cancer cell lines. However, the signalling mechanisms are still
      unclear. In this study, we investigated the effect of BCG on cAMP production and
      its role in regulating interleukin-6 expression in the human bladder cancer cell
      line, MGH. After 1 hr exposure to BCG, IL-6 gene expression in MGH cells
      increased by 2.5-3-fold and cAMP production increased by 8-10-fold in a time- and
      dose-dependent manner. BCG-induced cAMP production was inhibited by both
      antifibronectin antibody and an adenylate cyclase inhibitor, SQ22536 in a dose
      dependent way. In the presence of SQ22536, IL-6 expression in MGH cells was also
      greatly reduced. Furthermore, cAMP-dependent kinase inhibitors H7 and HA1004 also
      inhibited BCG-induced IL-6 expression in MGH, with HA1004 being much less
      effective than H7. Thus, BCG induces cAMP production and may regulate interleukin
      6 expression partially via a cAMP-dependent pathway in human bladder cancer
      cells.

PMID- 11841805
TI  - Effects of 5-aminoisoquinolinone, a water-soluble, potent inhibitor of the
      activity of poly (ADP-ribose) polymerase, in a rodent model of lung injury.
AB  - Poly (ADP-ribose) polymerase (PARP), a nuclear enzyme activated by strand breaks
      in DNA, plays an important role in the tissue injury associated with ischaemia-
      reperfusion injury and inflammation. The aim of the present study was to evaluate
      the effects of a novel and potent inhibitor of PARP activity on neutrophil
      recruitment in the acute inflammation induced by zymosan-activated plasma. Intra
      thoracic administration of zymosan-activated plasma leads to an increase in
      neutrophil infiltration of the lung at 24hr. The potent PARP inhibitor 5
      aminoisoquinolinone (5-AIQ) reduced the degree of lung injury and attenuated the
      expression of P-selectin and ICAM-1 as well as the recruitment of neutrophils
      into the injured lung. The up-regulation/expression of P-selectin and ICAM-1 in
      human endothelial cells exposed to oxidative stress (peroxynitrite) or to a pro
      inflammatory cytokine (tumor necrosis factor alpha, TNFalpha) was also attenuated
      by 5-AIQ. These findings provide the first evidence that the activation of PARS
      participates in neutrophil-mediated lung injury by regulating the expression of P
      selectin and ICAM-1.

PMID- 11841807
TI  - Identification of the phospholipase A(2) isoforms that contribute to arachidonic
      acid release in hypoxic endothelial cells: limits of phospholipase A(2)
      inhibitors.
AB  - Changes in endothelium functions during ischemia are thought to be of importance
      in numerous pathological conditions, with, for instance, an increase in the
      release of inflammatory mediators like prostaglandins. Here, we showed that
      hypoxia increases phospholipase A(2) (PLA(2)) activity in human umbilical vein
      endothelial cells. Both basal PLA(2) activity and PG synthesis are sensitive to
      BEL and AACOCF3, respectively, inhibitors of calcium-independent PLA(2) (iPLA(2))
      and cytosolic PLA(2) (cPLA(2)), while OPC, an inhibitor of soluble PLA(2)
      (sPLA(2)) only inhibited the hypoxia-induced AA release and PGF(2alpha)
      synthesis. Hypoxia does not alter expression of iPLA(2), sPLA(2) and cPLA(2) and
      cycloheximide did not inhibit PLA(2) activation, indicating that hypoxia-induced
      increase in PLA(2) activity is due to activation rather than induction. However,
      mRNA levels for sPLA(2) displayed a 2-fold increase after 2 hr incubation under
      hypoxia. BAPTA, an intracellular calcium chelator, partially inhibited the AA
      release in normoxia and in hypoxia. Direct assays of specific PLA(2) activity
      showed an increase in sPLA(2) activity but not in cPLA(2) activity after 2hr
      hypoxia. Taken together, these results indicate that the hypoxia-induced increase
      in PLA(2) activity is mostly due to the activation of sPLA(2).

PMID- 11841806
TI  - The involvement of L-gamma-glutamyl-L-cysteinyl-glycine (glutathione/GSH) in the
      mechanism of redox signaling mediating MAPK(p38)-dependent regulation of pro
      inflammatory cytokine production.
AB  - Redox regulation of mitogen-activated protein kinase (MAPK(p38))-mediated pro
      inflammatory cytokine production is not well characterized in the alveolar
      epithelium. It was hypothesized that the involvement of the MAPK(p38) pathway in
      regulating lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-alpha and
      interleukin-6 secretion is redox-sensitive and affected by NAC, an antioxidant
      and a precursor of glutathione, and L-buthionine-(S,R)-sulfoximine, an
      irreversible inhibitor of gamma-glutamylcysteine synthetase, the rate-limiting
      enzyme in GSH biosynthesis. Exposure of fetal alveolar type II epithelial cells
      to Escherichia coli-derived LPS induced, in a time-dependent manner, the
      phosphorylation/activation of MAPK(p38) (peak at 15min). In addition, LPS up
      regulated the phosphorylation of MAPK(p38) in a dose-dependent manner. The effect
      of LPS on the MAPK(p38) pathway was associated with the activation of MAPK
      activated protein kinase, which phosphorylated the small 27kDa heat-shock protein
      (Hsp27). LPS induced the phosphorylation of Hsp27 in a time- and dose-dependent
      manner. Selective blockage of the MAPK(p38) pathway by a pyridinyl-imidazole (SB
      203580) abrogated LPS-induced release of TNF-alpha and IL-6. Pre-treatment with
      NAC reduced LPS-mediated secretion of TNF-alpha and IL-6. Incubation of cells
      with NAC induced intracellular accumulation of GSH, but reduced the concentration
      of GSSG. On the other hand, pre-treatment with BSO augmented LPS-mediated
      secretion of TNF-alpha and IL-6. In addition, BSO induced intracellular
      accumulation of GSSG, but reduced the concentration of GSH. Whereas NAC blocked
      the phosphorylation/activation of MAPK(p38), BSO amplified the LPS-mediated
      effect on MAPK(p38). These results indicated that intracellular redox signaling
      plays an important role in regulating LPS-induced activation of the MAPK(p38)
      pathway and MAPK(p38)-mediated regulation of LPS-dependent inflammatory cytokine
      production in the alveolar epithelium.

PMID- 11841808
TI  - Differential regulation of multidrug resistance-associated protein 2 (MRP2) and
      cytochromes P450 2B1/2 and 3A1/2 in phenobarbital-treated hepatocytes.
AB  - Multidrug resistance-associated protein 2 (MRP2) is a drug efflux pump found at
      the biliary pole of hepatocytes. In the present study, we have investigated its
      expression in response to phenobarbital, a liver tumor promoter known to up
      regulate hepatic cytochromes P450 (CYPs), such as CYP2B1/2 and CYP3A1/2. MRP2
      mRNA and protein levels were found to be markedly increased in both primary rat
      and human hepatocytes exposed to phenobarbital. However, features of this up
      regulation, especially the dose-response, were different from those of the
      induction of CYP2B1/2 and CYP3A1/2. In addition, hepatic MRP2 expression remained
      unaltered in rats treated by phenobarbital that, by contrast, increased CYP2B1/2
      and CYP3A1/2 gene expression in the liver. Therefore, MRP2 and CYPs appeared
      differently regulated in response to phenobarbital in both in vivo and in vitro
      situations, suggesting that cellular and molecular mechanisms underlying up
      regulation of MRP2 are, at least in part, unrelated to those operating for CYPs.
      Phenobarbital-related MRP2 induction in primary rat hepatocytes was associated
      with some phenotypic effects of the barbiturate, such as prolonged cell survival
      and inhibition of cell proliferation. Phenobarbital also inhibited growth of
      human hepatoma HepG(2) cells and increased their level of MRP2 gene expression.
      Such results may favor a putative relationship between phenobarbital-mediated
      MRP2 regulation in cultured liver parenchymal cells and alteration of cell cycle
      and survival.

PMID- 11841809
TI  - Interaction of metal ions with D-glucobenzothiazoline: isolation and
      characterization of the resultant products.
AB  - Six different metal-ion complexes of D-glucobenzothiazoline were synthesized and
      characterized by analytical and spectral techniques. Formation of different types
      of species (ML and ML(2)) were observed with Cu(2+), Ag(+), Cd(2+), Hg(2+), and
      Zn(2+) ions. Existence of an anomeric mixture in the case of the Cu(2+) complex
      is identified from the EPR spectra, and the results were further supported by the
      simulated spectra. The structures were proposed based on different studies.

PMID- 11841810
TI  - Biosynthetic studies on the alpha-glucosidase inhibitor acarbose: the chemical
      synthesis of dTDP-4-amino-4,6-dideoxy-alpha-D-glucose.
AB  - To study the biosynthesis of the pseudotetrasaccharide acarbose, dTDP-4-amino-4,6
      dideoxy-alpha-D-glucose (3) was prepared from galactose in 16 steps. After
      initial protecting-group manipulations, the 6-position of galactose was
      deoxygenated by hydride displacement of a tosylate. Similarly a tosyl group at
      the 4-position was displaced upon reaction with sodium azide. Conversion of the
      resulting glycoside to a glycosyl phosphate was accomplished by reaction of a
      glycosyl trichloroacetimidate with dibenzyl phosphate. Subsequent removal of the
      benzyl protecting groups and reduction of the azide by hydrogenation and coupling
      with an activated nucleoside phosphate gave dTDP-4-amino-4,6-dideoxy-alpha-D
      glucose.

PMID- 11841811
TI  - X-ray structure analysis of the sodium salt of beijeran.
AB  - The three-dimensional structure of the sodium salt of beijeran has been
      determined by X-ray fiber diffraction analysis. The acidic polysaccharide forms
      an extended twofold helix. Two chains are nestled tightly in a monoclinic unit
      cell of dimensions a=12.72, b=11.41, c (fiber axis)=24.62 A and gamma=123.7
      degree in an antiparallel fashion. In the crystalline lattice, helices are
      stacked tightly to form a thick sheet along the vertical plane passing through
      the short diagonal of the basal net. Adjacent sheets associate via a network of
      sodium ions and water molecules embedded between them. The morphology of sodium
      beijeran in the solid state is consistent with its observed rheological
      properties.

PMID- 11841812
TI  - Biosynthesis of a substituted cellulose from a mutant strain of Xanthomonas
      campestris.
AB  - In Xanthomonas campestris the genes involved in polysaccharide (xanthan)
      biosynthesis are located in a gene cluster (gum) of 16 kb. A Tn5 insertion mutant
      with a reduced slimy phenotype has been characterized. This mutant failed to
      produce the pentasaccharide repeating-unit of xanthan. Only three sugars were
      transferred to the prenyl phosphate intermediate. Several lines of evidence
      suggested that the lipid-associated saccharide was the trisaccharide reducing end
      of the pentasaccharide from the wild-type strain. This trisaccharide was built up
      from UDP-Glc and GDP-Man, and a glucose residue was at the reducing end, linked
      to an allylic prenol through a diphosphate bridge. Results from one- or two-stage
      reactions showed that the trisaccharide-P-P-polyprenol was the precursor of the
      polymer. This new polymer, a polytrisaccharide, was detected also in vivo. The
      transposon responsible for the mutation was located within gumK gene. Therefore,
      this gene encodes for the glycosyltransferase IV, which catalyses the transfer of
      glucuronic acid to the lipid-linked beta-D-Manp-(1-->3)-beta-D-Glcp-(1-->4)-beta
      D-Glcp trisaccharide. A recombinant plasmid with the whole gum cluster restored
      the wild type phenotype.

PMID- 11841813
TI  - Production of highly phosphorylated glycopolymers by expression of R1 in
      Escherichia coli.
AB  - The possible involvement of the starch bound R1 protein from potato (Solanum
      tuberosum L.) in the phosphorylation of starch was investigated by functional
      expression and characterisation of R1 in Escherichia coli. By expression of R1 in
      E. coli it is shown that it is possible to produce glycopolymers, e.g., glycogen,
      with an increased degree of phosphate substitution. The expression of R1 in E.
      coli resulted in a sixfold increase in glycogen bound phosphate and in an
      increased accumulation of glycogen leading to a glycogen excess (gex) phenotype.
      There was an overall shift in the unit-chain length of the isolated glycogen
      towards smaller degrees of polymerisation. The pleiotropic effects on the
      glycogen biosynthetic and amylolytic enzyme activities was investigated and
      showed an increase in ADPglucose pyrophosphorylase activity, as well as a
      decrease in exo-amylolytic activity. These results are discussed in relation to
      starch phosphorylation and a possible role of R1 in this respect.

PMID- 11841814
TI  - Structural analysis and chemical depolymerization of the capsular polysaccharide
      of Streptococcus pneumoniae type 1.
AB  - NMR spectroscopy can be used to characterize bacterial polysaccharides such as
      that of Streptococcus pneumoniae type 1 which is a component of the 23-valent
      pneumococcal vaccine in clinical use. This particular polysaccharide gives NMR
      spectra with wide lines apparently due to restricted molecular mobility and chain
      flexibility which leads to rapid dipolar T(2) relaxation limiting the possibility
      of detailed spectral analysis. Removal of O-acetyl groups found on approximately
      two thirds of the repeating subunits of pneumococcal type 1 capsule leads to
      narrower NMR lines facilitating a complete assignment of the 1H and 13C NMR
      spectra. Degradation of the polysaccharide by periodate oxidation followed by
      base treatment leads to an oligosaccharide fragment of approximately three
      repeating trisaccharide units. This oligosaccharide has narrow NMR lines and 1H
      and 13C assignments very similar to those of the O-deacetylated polysaccharide.
      In the native polysaccharide, O-acetyl groups are located on the 2- and 3
      positions of the 4-linked galacturonic acid residue providing protection against
      periodate oxidation. Analysis of NOESY spectra combined with molecular modeling
      of the oligosaccharide shows that flexibility occurs in certain of the saccharide
      linkages.

PMID- 11841815
TI  - Kinetics and mechanism of Ru(III) and Hg(II) co-catalyzed oxidation of D
      galactose and D-ribose by N-bromoacetamide in perchloric acid.
AB  - Kinetics of oxidation of reducing sugars D-galactose (Gal) and D-ribose (Rib) by
      N-bromoacetamide (NBA) in the presence of ruthenium(III) chloride as a
      homogeneous catalyst and in perchloric acid medium, using mercuric acetate as a
      scavenger for Br(minus sign) ions, as well as a co-catalyst, have been
      investigated. The kinetic results indicate that the first-order kinetics in NBA
      at lower concentrations tend towards zero order at its higher concentrations. The
      reactions follow identical kinetics, being first order in the [sugar] and
      [Ru(III)]. Inverse fractional order in [H(+)] and [acetamide] were observed. A
      positive effect of [Hg(OAc)(2)] and [Cl(minus sign)] was found, whereas a change
      in ionic strength (mu) has no effect on oxidation velocity. Formic acid and D
      lyxonic acid (for Gal) and formic acid and L-erythronic acid (for Rib) were
      identified as main oxidation products of reactions. The various activation
      parameters have been computed and recorded. A suitable mechanism consistent with
      experimental findings has been proposed.

PMID- 11841816
TI  - Quantum mechanical and NMR spectroscopy studies on the conformations of the
      hydroxymethyl and methoxymethyl groups in aldohexosides.
AB  - The potential energy surfaces of the hydroxymethyl and methoxymethyl groups in
      methyl hexopyranosides have been extensively studied, employing quantum
      mechanical calculations and high resolution NMR data. The structure and energy of
      the C-5-C-6 rotamers were calculated at the B3LYP level of the density functional
      theory (DFT). For all, geometry optimizations were carried out for 264 conformers
      of 16 methyl D-gluco- and methyl D-galactopyranoside derivatives 1-16 at the
      B3LYP/6-31G** level. For all calculated minima, single-point calculations were
      performed at the B3LYP/6-311++G** level. Solvent effects were considered using a
      self-consistent reaction field method. Values of the vicinal coupling constants
      3J(H-5-H-6R), 3J(H-5-H-6S), 3J(C-4-H-6R), and 3J(C-4-H-6S) for methyl D
      glucopyranosides, methyl D-galactopyranosides and their 6-O-methyl derivatives 9
      16 were measured in two solvents, methanol and water. The calculated gg, gt, and
      tg rotamer populations of the hydroxymethyl and methoxymethyl groups in 9-16
      agreed well with experimental data. The results clearly showed that the
      population of gg, gt, and tg rotamers is sensitive to solvent effects. It was
      concluded that the preference of rotamers in 1-16 is due to the hydrogen bonding
      and solvent effects.

PMID- 11841817
TI  - New methods for the synthesis of N-benzoylated uridine and thymidine derivatives;
      a convenient method for N-debenzoylation.
AB  - An improved procedure for the synthesis of N-benzoyl-2',3'-O-isopropylidene
      uridine via one-step selective N-benzoylation of 2',3' -O-isopropylidene uridine
      has been developed. An efficient synthetic route to N-benzoyl thymidine via
      initial tribenzoylation, followed by selective hydrolysis of the benzoates is
      also described. De-N-benzoylation of N-benzoylated thymidine and uridine
      derivatives can be conveniently effected under neutral conditions, by heating
      with benzyl alcohol.

PMID- 11841818
TI  - Characterization of O-acetyl-(4-O-methylglucurono)xylan isolated from birch and
      beech.
AB  - The structures of water-soluble birch and beech xylans, extracted from
      holocellulose using dimethyl sulfoxide, were determined employing 1H and 13C NMR
      spectroscopy together with chemical analysis. These polysaccharides were found to
      be O-acetyl-(4-O-methylglucurono)xylans containing one 4-O-methylglucuronic acid
      substituent for approximately every 15 D-xylose residues. The average degree of
      acetylation of the xylose residues in these polymers was 0.4. The presence of the
      structural element -->4)[4-O-Me-alpha-D-GlcpA-(1-->2)][3-O-Ac]-beta-D-Xylp-(1-->
      was demonstrated. Additional acetyl groups were present as substituents at C-2
      and/or C-3 of the xylopyranosyl residues. Utilizing size-exclusion chromatography
      in combination with mass spectroscopy, the weight-average molar masses (and
      polydispersities) were shown to be 8000 (1.09) and 11,100 (1.08) for birch and
      beech xylan, respectively.

PMID- 11841821
TI  - Phase separations of alpha-tocopherol in aqueous dispersions of
      distearoylphosphatidylethanolamine.
AB  - The effect of alpha-tocopherol on the structure and thermotropic phase behaviour
      of distearoylphosphatidylethanolamine was examined by using synchrotron X-ray
      diffraction methods. There was evidence that alpha-tocopherol does not distribute
      randomly in the dispersed phospholipid but instead phospholipid phases enriched
      in alpha-tocopherol are formed. Heating codispersions from lamellar gel phase
      induced formation of hexagonal-II phase at temperatures below the main transition
      of the pure phospholipid and which were enriched in alpha-tocopherol.
      Codispersions containing 5 or 10 mol% alpha-tocopherol were induced to form a
      cubic phase at temperatures above the lamellar to hexagonal-II phase transition.
      Such phases were not observed in codispersions containing 2.5 or 20 mol% alpha
      tocopherol in which only lamellar and hexagonal-II phases were formed. The space
      group of the cubic phases were tentatively assigned as Pn3m. Equilibration of
      codispersions at 4 degrees C results in the formation of lamellar crystalline
      phases enriched in alpha-tocopherol and phase separated domains of pure
      phospholipid. Two lamellar crystalline phases were characterized on the basis of
      their particular wide-angle X-ray scattering patterns. The lamellar crystalline
      phases were also distinguished from other lamellar phases of the pure
      phospholipid by the lamellar repeat. Partitioning of alpha-tocopherol into
      phosphatidylethanolamine domains in membranes may introduce instability into the
      structure.

PMID- 11841822
TI  - Sphingomyelinase cleavage of sphingomyelin in pure and mixed lipid membranes.
      Influence of the physical state of the sphingolipid.
AB  - Sphingomyelin hydrolysis by sphingomyelinase is essential in regulating membrane
      levels of ceramide, a well-known metabolic signal. Since natural sphingomyelins
      have a gel-to-fluid transition temperature in the range of the physiological
      temperatures of mammals and birds, it is important to understand the influence of
      the physical state of the lipid on the enzyme activity. With that aim, large
      unilamellar vesicles consisting of pure egg sphingomyelin (gel-to-fluid
      crystalline transition temperature ca. 39 degrees C) were treated with
      sphingomyelinase in the temperature range 10-70 degrees C. The vesicles were also
      examined by differential scanning calorimetry (DSC). Shingomyelinase was active
      on pure sphingomyelin bilayers, leading to concomitant lipid hydrolysis, vesicle
      aggregation, and leakage of aqueous liposomal contents. Enzyme activity was found
      to be much higher when the substrate was in the fluid than when it was in the gel
      state. Sphingomyelinase activity was found to exhibit lag times, followed by
      bursts of activity. Lag times decreased markedly when the substrate went from the
      gel to the fluid state. When egg phosphatidylcholine, or egg
      phosphatidylethanolamine were included in the bilayer composition together with
      sphingomyelin, sphingomyelinase activity at 37 degrees C, that was negligible for
      the pure sphingolipid bilayers, was seen to increase with the proportion of
      glycerophospholipid, while the latency times became progressively shorter. A DSC
      study of the mixed-lipid vesicles revealed that both phosphatidylcholine and
      phosphatidyletanolamine decreased in a dose-dependent way the transition
      temperature of sphingomyelin. Thus, as those glycerophospholipids were added to
      the membrane composition, the proportion of sphingomyelin in the fluid state at
      37 degrees C increased accordingly, in this way becoming amenable to rapid
      hydrolysis by the enzyme. Thus sphingomyelinase requires the substrate in bilayer
      form to be in the fluid state, irrespective of whether this is achieved through a
      thermotropic transition or by modulating bilayer composition.

PMID- 11841823
TI  - Component-specific surface and physiological activity in bovine-derived lung
      surfactants.
AB  - Composition, surface activity and effects on pressure-volume (P-V) mechanics are
      examined for lavaged calf lung surfactant (LS) and the clinical exogenous
      surfactants Infasurf and Survanta. Lavaged LS and Infasurf had closely-matching
      compositions of phospholipids and neutral lipids. Survanta had higher levels of
      free fatty acids and triglycerides consistent with its content of added synthetic
      palmitic acid and tripalmitin. Infasurf and Survanta both contained less total
      protein than LS because of extraction with hydrophobic solvents, but the total
      protein content relative to phospholipid in Survanta was about 45% lower than in
      Infasurf. This difference was primarily due to surfactant protein (SP)-B, which
      was present by ELISA at a mean weight percent relative to phospholipid of 1.04%
      in LS, 0.90% in Infasurf, and 0.044% in Survanta. Studies on component fractions
      separated by gel permeation chromatography showed that SP-B was a major
      contributor to the adsorption, dynamic surface activity, and P-V mechanical
      effects of Infasurf, which approached whole LS in magnitude. Survanta had lower
      adsorption, higher minimum surface tension, and a smaller effect on surfactant
      deficient P-V mechanics consistent with minimal contributions from SP-B. Addition
      of 0.05% by weight of purified bovine SP-B to Survanta did not improve surface or
      physiological activity, but added 0.7% SP-B improved adsorption, dynamic surface
      tension lowering, and P-V activity to levels similar to Infasurf. The SP-B
      content of lung surfactants appears to be a crucial factor in their surface
      activity and efficacy in improving surfactant-deficient pulmonary P-V mechanics.

PMID- 11841824
TI  - Propofol, a general anesthetic, promotes the formation of fluid phase domains in
      model membranes.
AB  - The molecular site of anesthetic action remains an area of intense research
      interest. It is not clear whether general anesthetics act through direct binding
      to proteins or by perturbing the membrane properties of excitable tissues.
      Several studies indicate that anesthetics affect the properties of either
      membrane lipids or proteins. However, gaps remain in our understanding of the
      molecular mechanism of anesthetic action. Recent developments in membrane biology
      have led to the concept of small-scale domain structures in lipid and lipid-
      protein coupled systems. The role of such domain structures in anesthetic action
      has not been studied in detail. In the present study, we investigated the effect
      of anesthetics on lipid domain structures in model membranes using the
      fluorescent spectral properties of Laurdan (6-dodecanoyl-2-dimethylamino
      naphthalene). Propofol, a general anesthetic, promoted the formation of fluid
      domains in model membranes of dipalmitoyl phosphatidyl choline (DPPC) or mixtures
      of lipids of varying acyl chains (DPPC:DMPC dimyristoyl phosphatidyl choline
      1:1). The estimated size of these domains is 20--50 A. Based on these studies, we
      speculate that the mechanism of anesthetic action may involve effects on protein-
      lipid coupled systems through alterations in small-scale lipid domain structures.

PMID- 11841825
TI  - Effect of human Apo AIV against lipid peroxidation of very low density
      lipoproteins.
AB  - Recent studies have demonstrated that Apo AIV exerts a protective effect against
      atherosclerosis. Moreover, Qin et al. (Am. J. Physiol. 274 (1998) H1836) have
      demonstrated that Apo AIV, isolated from rat plasma, exerts an inhibitory effect
      against Cu(2+)-induced lipid peroxidation of intestinal lymph and LDL. The aim of
      the study was to investigate whether human Apo AIV exerts a protective effect
      against Cu(2+)-induced lipid peroxidation. Our results demonstrated that human
      Apo AIV exerted an inhibitory effect against Cu(2+) and AAPH induced lipid
      peroxidation of VLDL, as shown by the lower increase in the levels of TBARS and
      conjugated dienes in lipoproteins preincubated with Apo AIV. In addition, the
      tryptophan (Trp) and probe 2-(dimethylamino)-6-lauroylnaphthalene (Laurdan)
      fluorescence studies demonstrated that the modifications of spectral properties
      in both lipoproteins preincubated with Apo AIV were lower with respect to ox
      lipoproteins, suggesting that Apo AIV prevents the modification of physico
      chemical properties due to peroxidation.

PMID- 11841826
TI  - Synthesis and mesogenic properties of glycosyl diacylglycerols.
AB  - We synthesised glycosyl diacylglycerols bearing unsaturated or chiral methyl
      branched fatty acid chains. The thermotropism was measured with polarising
      microscopy and additionally the lyotropism with the contact preparation method.
      The synthesised compounds displayed thermotropic S(A) (lamellar), cubic and
      columnar phases and investigation of the lyotropic phase behaviour led to the
      observation of inverted bicontinuous cubic V(II) phases, lamellar L(alpha) phases
      and normal bicontinuous cubic V(I) phases. The phases are discussed with respect
      to the chemical structures that have been varied systematically to derive
      structure--property relationships.

PMID- 11841828
TI  - Highly cohesive monolayers of lipid derivatives of colchicine: a dynamics study.
AB  - Monolayers of lipid derivatives of colchicine spread at the air--water interface
      reach the thermodynamic equilibrium over an abnormally long period of time.
      Dynamics of this equilibration and the behavior of the film during compression-
      decompression cycles are observed by fluorescence microscopy. The
      thermodynamically disfavored structures observed are unrelated to previously
      described unusual shapes in the liquid expanded-gas coexistence regions. The
      relation between the cholesterol-like effect of the colchicinoid moiety, its
      propensity to dimerize, and the high viscosity of the monolayer are discussed.

PMID- 11841827
TI  - Copper-induced peroxidation of liposomal palmitoyllinoleoylphosphatidylcholine
      (PLPC), effect of antioxidants and its dependence on the oxidative stress.
AB  - In an attempt to deepen our understanding of the mechanisms responsible for
      lipoprotein peroxidation, we have studied the kinetics of copper-induced
      peroxidation of the polyunsaturated fatty acid residues in model membranes
      (small, unilamellar liposomes) composed of palmitoyllinoleoylphosphatidylcholine
      (PLPC). Liposomes were prepared by sonication and exposed to CuCl(2) in the
      absence or presence of naturally occurring reductants (ascorbic acid (AA) and/or
      alpha-tocopherol (Toc)) and/or a Cu(I) chelator (bathocuproinedisulfonic acid
      (BC) or neocuproine (NC)). The resultant oxidation process was monitored by
      recording the time-dependence of the absorbance at several wavelengths. The
      observed results reveal that copper-induced peroxidation of PLPC is very slow
      even at relatively high copper concentrations, but occurs rapidly in the presence
      of ascorbate, even at sub-micromolar copper concentrations. When added from an
      ethanolic solution, tocopherol had similar pro-oxidative effects, whereas when
      introduced into the liposomes by co-sonication tocopherol exhibited a marked
      antioxidative effect. Under the latter conditions, ascorbate inhibited
      peroxidation of the tocopherol-containing bilayers possibly by regeneration of
      tocopherol. Similarly, both ascorbate and tocopherol exhibit antioxidative
      potency when the PLPC liposomes are exposed to the high oxidative stress imposed
      by chelated copper, which is more redox-active than free copper. The biological
      significance of these results has yet to be evaluated.

PMID- 11841829
TI  - The formation of helical tubular vesicles by binary monolayers containing a
      nickel-chelating lipid and phosphoinositides in the presence of basic
      polypeptides.
AB  - Binary lipid monolayers consisting of equimolar proportions of a phosphoinositide
      and a nickel-chelating lipid formed helical tubular vesicular structures, which
      appeared to be induced and/or stabilized by myelin basic protein (MBP). Another
      basic polypeptide, poly-L-lysine, had a similar effect but not to as great a
      degree as MBP; the proteins thus appeared to act as polycations. Although, the
      nickel-chelating lipid is a synthetic product, other endogenous divalent cations
      such as Zn(2+), as well as phosphoinositides, are integral and dynamic components
      of the myelin sheath in vivo. There, comparable helical tubular structures might
      represent a means for sequestration of these lipids into domains of high local
      concentration, perhaps in regions where the membrane is greatly curved.

PMID- 11841831
TI  - Calcium and oxidative stress: from cell signaling to cell death.
AB  - Reactive oxygen and nitrogen species can be used as a messengers in normal cell
      functions. However, at oxidative stress levels they can disrupt normal
      physiological pathways and cause cell death. Such a switch is largely mediated
      through Ca(2+) signaling. Oxidative stress causes Ca(2+) influx into the
      cytoplasm from the extracellular environment and from the endoplasmic reticulum
      or sarcoplasmic reticulum (ER/SR) through the cell membrane and the ER/SR
      channels, respectively. Rising Ca(2+) concentration in the cytoplasm causes
      Ca(2+) influx into mitochondria and nuclei. In mitochondria Ca(2+) accelerates
      and disrupts normal metabolism leading to cell death. In nuclei Ca(2+) modulates
      gene transcription and nucleases that control cell apoptosis. Both in nuclei and
      cytoplasm Ca(2+) can regulate phosphorylation/dephosphorylation of proteins and
      can modulate signal transduction pathways as a result. Since oxidative stress is
      associated with many diseases and the aging process, understanding how oxidants
      alter Ca(2+) signaling can help to understand process of aging and disease, and
      may lead to new strategies for their prevention.

PMID- 11841832
TI  - Thioredoxin-mediated redox control of human T cell lymphotropic virus type I
      (HTLV-I) gene expression.
AB  - Thioredoxin (TRX) is a small ubiquitous protein with multiple biological
      functions, including the thiol-mediated redox-regulation of gene expression. We
      have previously demonstrated that human TRX is overexpressed as a major protein
      oxidoreductase in human T cell lymphotropic virus type I (HTLV-I)-infected cells.
      In the present study, we investigated the relationship between TRX and viral gene
      expression in HTLV-I infection. To study the mechanism that causes overexpression
      of TRX in HTLV-I-infected cells, we first examined the effect of the HTLV-I
      transactivator, Tax, on TRX expression. Induction of HTLV-I Tax protein increased
      the expression of TRX protein in a Tax-transfected Jurkat cell line, JPX-9.
      Moreover, chloramphenicol acetyltransferase (CAT) analysis with a reporter gene
      containing the TRX promoter revealed that Tax activates the transcription of TRX
      gene. To study the role of overexpressed TRX in HTLV-I infection, we next
      examined the effect of TRX on HTLV-I long terminal repeat (LTR)-mediated
      transcription using CAT analysis. In an HTLV-I-infected human T cell line MT-2,
      the HTLV-I LTR transactivation was suppressed by the overexpression of wild-type
      TRX, but activated by the introduction of inactive mutant TRX. Moreover, in HTLV
      I negative Jurkat T cells, the HTLV-I LTR transactivation induced by Tax was also
      repressed by overexpression of wild-type TRX. Because cellular redox changes were
      shown to affect the HTLV-I gene expression, it is likely that TRX modulates the
      HTLV-I gene expression by regulating cellular redox state. Taken together, these
      findings suggest that overexpressed TRX, which is induced by HTLV-I Tax, may play
      an important role in HTLV-I infection through the negative regulation of viral
      gene expression.

PMID- 11841833
TI  - Differential effects of the antioxidant alpha-lipoic acid on the proliferation of
      mitogen-stimulated peripheral blood lymphocytes and leukaemic T cells.
AB  - The effects of the antioxidant alpha-lipoic acid (LA) on the proliferation of
      mitogen-stimulated human peripheral blood lymphocytes (HPBL) were investigated in
      comparison to its effects on the proliferation of two leukaemic T cell lines,
      Jurkat and CCRF-CEM. At low mM concentrations, LA inhibited in a dose-dependent
      manner DNA synthesis of HPBL stimulated with either phorbol myristate acetate
      (PMA) in combination with ionomycin (IoM), or phytohaemagglutinin (PHA). At
      similar concentrations, LA inhibited the proliferation of Jurkat and CCRF-CEM
      cells. However, LA was preferentially cytotoxic to the leukaemic cell lines. The
      selective toxicity of LA to Jurkat cells was shown by electron microscopy (EM) to
      be due to the induction of apoptosis. Furthermore, LA had different effects on
      the secretion of interleukin-2 (IL-2) and steady-state levels of IL-2 mRNA in
      mitogen-stimulated HPBL depending on the mitogens used. LA dramatically increased
      the induction of IL-2 mRNA and IL-2 protein secretion in PMA/IoM-stimulated HPBL,
      whereas it inhibited these in HPBL stimulated with PHA. The differential effects
      of LA on normal and leukaemic T lymphocytes may indicate a new route towards
      development of therapeutic agents.

PMID- 11841834
TI  - Intracellular thiol redox status of macrophages directs the Th1 skewing in
      thioredoxin transgenic mice during aging.
AB  - We have been proposing the functional distinction of two classes of macrophages
      (Mp), namely the reductive macrophages (RMp) with high intracellular content of
      glutathione (GSH) and the oxidative macrophages (OMp) with reduced content. At
      the same time we have been investigating the variation of RMp/OMp balance during
      aging of mice, especially in relation to the age related onset of autoimmune
      diseases. In this paper we have investigated the Th1/Th2 balance of thioredoxin
      (TRX) transgenic (Tg) mice, with prolonged life longevity, during aging in the
      context of the intracellular redox status of Mp, which has been hypothesized to
      be crucial in regulating the Th1/Th2 balance. It was confirmed that peritoneal
      resident Mp of Tg mice showed the higher GSH/GSSG ratios compared with that of
      age matched wild type (WT) mice. The predominance of RMp was associated with the
      sustained maintenance of Th1 prevalence during aging until 2 years in Tg mice,
      whereas WT littermates showed rapid polarization to Th2 around the age of 8
      months. The Tg mice showed elevation of IFN-gamma and reduction of IL-10 with
      moderate change of IL-4 produced by CD4+ T cells. The WT mice showed inverse
      changes of IFN-gamma/IL-4 and IFN-gamma/IL-10 ratios during aging. In addition,
      IL-10 production by Mp was dramatically reduced in aged Tg mice. Thus, TRX Tg
      mice may be useful to investigate the contribution of the anti-oxidant defense
      mechanism during aging accompanied with increasing oxidative stress.

PMID- 11841835
TI  - Thioredoxin-(dithiol-)linked inactivation of elastase.
AB  - Following inactivation by the alpha-1-antitrypsin (AAT) inhibitor, the protease
      elastase was reduced by thioredoxin, itself reduced by NADPH and NADP-thioredoxin
      reductase (NTR). Under these conditions, reduction of enzyme disulfide groups was
      accompanied by loss of more than 60% of the activity measured following
      dissociation of the enzyme-inhibitor complex with NaCl. The inhibitor was
      required (1) to prevent proteolysis of both reduced thioredoxin and NTR and (2)
      to assess the progress of the reduction reaction. At elevated temperature,
      elastase was also reduced by dithiols (dithiothreitol and lipoic acid) but not by
      monothiols (reduced glutathione, beta-mercaptoethanol). When reduced by dithiols
      under these conditions, the enzyme digested itself. Self-digestion was
      independent of the antitrypsin inhibitor and was proportional to temperature in
      the 37-50 degree C range. These findings open the door to a new mode of
      regulation of elastase and to possible new therapies for treating diseases
      associated with the enzyme.

PMID- 11841836
TI  - Thioredoxin as a biomarker for oxidative stress in patients with rheumatoid
      arthritis.
AB  - There is no doubt that oxidative stress occurs in patients with rheumatoid
      arthritis (RA) and play an important role in both inflammation and destruction of
      RA joints. Thioredoxin (TRX) is a ubiquitous redox-active protein and is known to
      be induced in several cells against oxidative stress and to be secreted
      extracellularly. To clarify whether plasma thioredoxin levels could be a marker
      for oxidative stress in patients with RA, we measured plasma TRX levels in
      patients with RA using a sensitive sandwich enzyme-linked immunosorbent assay
      (ELISA) and investigated its relationship to TRX concentrations in the
      inflammatory joints. We have found that the plasma TRX levels of RA patients were
      significantly higher than those of normal subjects (86.8 +/-54.1 ng/ml versus
      38.6 +/-18.5 ng/ml, P<0.0001). The plasma levels were correlated with the disease
      activity of RA and also with serum C-reactive protein (CRP) values (P<0.01). The
      concentration of TRX in synovial fluid (SF) from RA was 353.3 +/- 220.1 ng/ml
      (mean +/- S.D.) which was significantly higher than that in SF from
      osteoarthritis patients (70.6 +/- 31.0 ng/ml, P<0.0001). The SF TRX concentration
      was significantly correlated with the number of leukocytes infiltrating in SF and
      with the serum CRP levels. The serum TRX levels were significantly positively
      correlated with the SF TRX concentrations in RA patients (P<0.05). By the
      histological examination for synovial tissue of RA patients, TRX was shown to be
      present on the surface of synovial lining layer as well as in the
      leukocytes.Moreover, urinary excretion of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a
      biomarker of oxidative DNA damage by endogenously generated oxygen radicals, was
      significantly higher in RA patients than in healthy subjects (11.55 +/- 4.71
      versus 7.76 +/- 2.26 ng/mg creatinine, P<0.0001). Plasma TRX levels were
      significantly correlated with urinary excretion of 8-OHdG (P<0.005). We concluded
      that plasma TRX level is a new biomarker for the disease activity of RA and may
      reflect higher levels of oxidative stress in RA patients.

PMID- 11841837
TI  - Protein glutathionylation: coupling and uncoupling of glutathione to protein
      thiol groups in lymphocytes under oxidative stress and HIV infection.
AB  - We show here that exposure to oxidative stress induces glutathione (GSH)
      modification of protein cysteinyl residues (glutathionylation) in T cell blasts.
      Treating the cells with the oxidant diamide induces thiolation of a series of
      proteins that can be detected by 2D electrophoresis when 35S-cysteine is used to
      label the intracellular GSH pool. This thiolation is reversible, proteins are
      rapidly dethiolated and GSH is released from proteins once the oxidants are
      washed and the cells are allowed to recover. Dethiolation is dependent on the
      availability of GSH and thiols, since it is inhibited by GSH-depleting agents and
      improved by N-acetyl-L-cysteine (NAC). The capacity of these agents to reverse
      glutathionylation is diminished in T cell blasts infected in vitro with HIV,
      which is known to cause oxidative stress. Consistent with these findings, the
      activity of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), an enzyme known to
      be inhibited by glutathionylation, is inhibited in diamide-treated cells and
      recovers rapidly when cells are allowed to dethiolate. Further, GAPDH activity is
      diminished by GSH-depleting agents and augmented by NAC. Thus, reversible
      glutathionylation of proteins can rapidly shift the activity of a key metabolic
      enzyme and thereby result in dramatic, reversible changes in cellular metabolism.

PMID- 11841838
TI  - Baicalin induces apoptosis via mitochondrial pathway as prooxidant.
AB  - Baicalin is a flavonoid and a major component of a herbal medicine, Sho-saiko-to,
      which is commonly used for treatment of chronic hepatitis in Japan and China.
      Flavonoids including baicalin have been reported to not only function as anti
      oxidants but also cause cytotoxic effect. We investigated the mechanism of
      baicalin-induced cytotoxicity in leukemia-derived T cell line, Jurkat cells. When
      cells were cultured with 50-200 microg/ml baicalin for 6h, caspase-3 was
      activated and then cells fell into apoptosis. Induction of apoptosis by baicalin
      was accompanied with the marginal generation of intracellular reactive oxygen
      species (ROS), the increase of the cytosolic fractions of cytochrome c, and the
      disruption of mitochondrial transmembrane potential (DeltaPsi(m)) prior to the
      activation of caspase-3. The pre-culture with 5 mM of buthionine sulfoximine
      (BSO), an inhibitor of glutathione (GSH) synthesis, facilitated baicalin-induced
      disruption of DeltaPsi(m) and induction of apoptosis. The pre-culture with N
      benzyloxycarbonyl-valyl-alanyl-aspartyl fluoromethylketone (Z-VAD-fmk), a pan
      caspase inhibitor, partially suppressed the induction of apoptosis. On the other
      hand, baicalin showed little toxic effect on peripheral blood mononuclear cells
      (PBMCs) from healthy volunteers. These results indicate that baicalin acts as a
      prooxidant and induces caspase-3 activation and apoptosis via mitochondrial
      pathway.

PMID- 11841839
TI  - Effects of a new anti-rheumatic drug KE-298 and its active metabolite: KE-758 on
      secretion of thioredoxin and on the level of intracellular glutathione in human
      monocytes and T cells.
AB  - Thioredoxin (TRX) and glutathione (GSH) are key regulators of the cellular
      balance of reduction/oxidation (redox). The impaired redox balance in joint
      cellular circumstances participates in immune dysfunctions seen in patients with
      rheumatoid arthritis (RA). We analyzed effects of a newly developed anti
      rheumatic drug, KE-298 (2-acetylthiomethyl-4-(4-methylphenyl)-4-oxobutanoic acid)
      and it is active metabolite; KE-758 (2-mercaptomethyl-4-(4-methylphenyl)-4
      oxobutanoic acid) on the secretion of TRX and the level of intracellular GSH in
      THP-1 cells, a human monocytic cell line and in Jurkat cells, a human T cell
      leukemia cell line, then we compared their effects with N-acetyl-L-cysteine
      (NAC). KE-298 (10-100 microg/ml) and KE-758 (10-100 microg/ml) as well as a high
      concentration of NAC (10mM) dose-dependently inhibited the secretion of TRX by
      THP-1 and Jurkat cells. RT-PCR analysis indicated that the suppressive effects of
      KE-298 and KE-758 on TRX secretion could be partly explained by the inhibition of
      TRX mRNA expression. On the other hand, KE-758 as well as a high concentration of
      NAC significantly increased the level of intracellular GSH. Thus, KE-298 is a
      novel sulphydryl drug which regulates the redox state of cellular circumstances.
      The potential of KE-298 to suppress the secretion of TRX and to increase the
      level of intracellular GSH may partly explain the efficacy in cases of RA.

PMID- 11841840
TI  - Liver nonparenchymal cells involved in hyporesponsiveness induced by portal vein
      injection of alloantigen.
AB  - INTRODUCTION: Intrahepatic injection of alloantigen prolongs allograft survival
      and inhibits T-lymphocyte release of both IL-2 and IFN-gamma but not IL-4. This
      suggests that intrahepatic processing of antigen lead to a predominance of Th2
      cell population with inhibition of Th1 cell type. This study examines the effects
      of hepatic nonparenchymal cells (NPCs) on T cell function and cytokine mRNA
      expression profiles. MATERIALS AND METHODS: Following portal vein (p.v.)
      injection of allogeneic splenic mononuclear cells (SMNC) in mice, heterotopic
      cardiac allograft survival and donor-specific immune responses were assessed. The
      cytokine profiles were evaluated in heart grafts and spleens from transplanted
      mice, or in recipient lymphocytes stimulated in vitro with alloantigen. The
      immunoregulatory role of NPCs from p.v. injected mice was evaluated. RESULTS:
      Transplanted mice with prolonged graft survival demonstrated increased IL-4, TGF
      beta and IL-10 and/or decreased IFN-gamma and IL-2 mRNA expression within the
      spleen and the transplanted graft. This correlated with increased antigen
      specific IL-4, IL-10 and TGF-beta expression in lymphocytes isolated from the
      p.v. injected mice. In mixed lymphocyte cultures using NPC from p.v. injected
      mice as regulatory cells, there was decreased proliferation of lymphocytes from
      the p.v. injected mice in response to allogeneic stimulation, associated with
      increased IL-4, TGF-beta and IL-10 production and decreased IFN-gamma and IL-2
      production. The regulatory effects of the NPC was reversed by prostaglandin E
      inhibitor. CONCLUSIONS: Interactions between allogeneic lymphocytes and NPCs
      results in an impaired Th1 response and preferential shift towards a Th2 cytokine
      response which may regulate allograft rejection.

PMID- 11841841
TI  - A DNA vaccine encoding the 42 kDa C-terminus of merozoite surface protein 1 of
      Plasmodium falciparum induces antibody, interferon-gamma and cytotoxic T cell
      responses in rhesus monkeys: immuno-stimulatory effects of granulocyte macrophage
      colony stimulating factor.
AB  - We have constructed a DNA plasmid vaccine encoding the C-terminal 42-kDa region
      of the merozoite surface protein 1 (pMSP1(42)) from the 3D7 strain of Plasmodium
      falciparum (Pf3D7). This plasmid expressed recombinant MSP1(42) after in vitro
      transfection in mouse VM92 cells. Rhesus monkeys immunized with pMSP1(42)
      produced antibodies reactive with Pf3D7 infected erythrocytes by IFAT, and by
      ELISA against yeast produced MSP1(19) (yMSP1(19)). Immunization also induced
      antigen specific T cell responses as measured by interferon-gamma production, and
      by classical CTL chromium release assays. In addition, immunization with
      pMSP1(42) primed animals for an enhanced antibody response to a subsequent boost
      with the recombinant yMSP1(19). We also evaluated Granulocyte-Macrophage Colony
      Stimulating Factor (GM-CSF) as an adjuvant for pMSP1(42.) We tested both rhesus
      GM-CSF expressed from a DNA plasmid, and E. coli produced recombinant human GM
      CSF. Plasmids encoding rhesus GM-CSF (prhGM-CSF) and human GM-CSF (phuGM-CSF)
      were constructed; these plasmids expressed bio-active recombinant GMCSF. Co
      immunization with a mixture of prhGM-CSF and pMSP1(42) induced higher specific
      antibody responses after the first dose of plasmid, but after three doses of DNA
      monkeys immunized with or without prhGM-CSF had the same final antibody titers
      and T cell responses. In comparison, rhuGM-CSF protein did not lead to
      accelerated antibody production after the first DNA dose. However, antibody
      titers were maintained at a slightly higher level in monkeys receiving GM-CSF
      protein, and they had a higher response to boosting with recombinant MSP1(19).
      The GM-CSF plasmid or protein appears to be less potent as an adjuvant in rhesus
      monkeys than each is in mice, and more work is needed to determine if GM-CSF can
      be a useful adjuvant in DNA vaccination of primates.

PMID- 11841842
TI  - Gender does not influence the susceptibility of C57BL/6 mice to develop chronic
      experimental autoimmune encephalomyelitis induced by myelin oligodendrocyte
      glycoprotein.
AB  - Multiple sclerosis (MS), an inflammatory demyelinating disease of the central
      nervous system (CNS), is more prevalent in females than males. It is well
      documented that a significant gender difference exits in the susceptibility of
      mice to develop experimental autoimmune encephalomyelitis (EAE), a model of MS,
      induced by myelin basic protein or proteolipid protein. In contrast, we report
      here that no significant difference between female mice and male mice with myelin
      oligodendrocyte glycoprotein (MOG)-induced EAE was observed in the incidence of
      disease, clinical course, histological findings in the CNS, T cell response and
      cytokine production of spleen cells to MOG, and anti-MOG IgG level in serum.
      These results suggest that gender-related difference in EAE depends on the
      encephalitogen and/or the strain of animals used. Given that MOG is a putative
      pathogenic myelin antigen in MS, the present findings may have implications for
      the pathogenesis of this disease.

PMID- 11841843
TI  - Endomorphins delay constitutive apoptosis and alter the innate host defense
      functions of neutrophils.
AB  - Recent studies have shown that opioid peptides are released from cells of the
      immune system during inflammation and stress, and are associated with altered
      immune responses. Moreover, concentrations of opioid peptides are increased in
      peripheral blood and at the sites of inflammatory reactions. The aim of this
      study was to evaluate immunological effects of opioid peptides endomorphins 1 and
      2 on constitutive apoptosis, superoxide anion production, hydrogen peroxide
      production, adhesion, phagocytosis, and chemotaxis of neutrophils. Neutrophils
      were isolated by peritoneal lavage from rats. Endomorphins 1 and 2 significantly
      delayed constitutive neutrophil apoptosis. The delay of neutrophil apoptosis was
      markedly attenuated by LY294002, a phosphoinositide 3-kinase inhibitor. Moreover,
      endomorphins 1 and 2 activated the phosphoinositide 3-kinase pathway as
      determined by phosphorylation of BAD. In contrast, endomorphins 1 and 2 blocked
      the production of superoxide anion and hydrogen peroxide by PMA-stimulated
      neutrophils. In addition, endomorphins 1 and 2 inhibited neutrophil adhesion to
      fibronectin. Moreover, endomorphins 1 and 2 potentiated neutrophil chemotaxis
      toward zymosan-activated serum and IL-8, respectively. However, endomorphins 1
      and 2 did not alter phagocytosis of Escherichia coli by neutrophils. These
      results suggest that endomorphins 1 and 2 may act to delay neutrophil apoptosis
      and alter the natural immune functions of neutrophils.

PMID- 11841844
TI  - Selective cleavage of human IgG by the matrix metalloproteinases, matrilysin and
      stromelysin.
AB  - We have shown that two of the matrix metalloproteinases (MMPs), matrilysin and
      stromelysin-1, are capable of cleaving all of the human IgG subclasses. The
      cleavage occurs at a conserved site in the CH(2) domain of the heavy chain of
      IgG, releasing a single chain Fc-like fragment. We have not been able to
      demonstrate cleavage of IgA, IgD, IgM or IgE classes, which lack the cleavage
      site, nor could we show cleavage of IgG by collagenase, gelatinase, macrophage
      metalloelastase or membrane-type (MT)-MMP. This cleavage of IgG, by separating
      the antigen-binding (Fabprime prime or minute)(2) from the Fc portion, will
      remove much of the immunoglobulins' functionality, e.g. complement fixation, Fc
      receptor binding. In the context of a tumour producing matrilysin or stromelysin,
      this may represent a way in which the tumour protects itself from ADCC. In
      inflamed or damaged tissues where plasma protein leakage occurs, degradation by
      MMPs may be a mechanism for clearance of IgG.

PMID- 11841845
TI  - Down regulation of B cells by immunization with a fusion protein of a self CD20
      peptide and a foreign IgG.Fc fragment.
AB  - In vivo studies of mice were performed to investigate whether auto-reactive
      antibodies specific for self CD20 antigen on B cells could be induced by
      immunizing with a CD20 peptide linked to a foreign, human IgG.Fc fragment through
      a T cell immunologically inert linker peptide and how such an auto-reactivity, if
      generated, would affect the levels of B cells. The dimeric Fc fusion protein
      containing the extracellular 44-amino acid portion of CD20, and the CH2-CH3
      domains of human gamma 1 immunoglobulin were prepared. After several subcutaneous
      immunizations with this CD20-Fc protein, mice produced anti-CD20 antibodies that
      can bind to native CD20 on normal B cells and B-lymphoma cells. In mice immunized
      with the CD20-Fc protein, the fraction of B cells in total peripheral blood
      lymphocytes decreased to about 40%, significantly lower than that of mice
      immunized with human IgG. In addition, antibody response towards an irrelevant
      bystander antigen, chicken ovalbumin, was weakened compared with that of mice
      immunized with human IgG. These results show that auto-reactive antibodies
      specific for CD20 can be induced by immunizing with an autologous CD20 peptide
      fused with a foreign IgG.Fc and that the auto-antibodies can partially reduce the
      levels of B cells and their response to other antigens.

PMID- 11841846
TI  - Expression of Notch ligands, Jagged1, 2 and Delta1 in antigen presenting cells in
      mice.
AB  - Notch1 is indispensable for T cell development. It is anticipated that Notch1 and
      other Notch receptors expressed on the surface of thymic T cell precursors are
      activated by ligands present on environmental cells, including antigen presenting
      cells (APCs), and involved in positive and negative selections. Notch receptors
      on peripheral T cells may also be activated by ligands on APCs. Here, we examined
      the expression pattern of three Notch ligands, Jagged1, 2 and Delta1 in APCs by
      an immunofluorescence cell staining method and a reverse transcriptase-polymerase
      chain reaction (RT-PCR) method. Peritoneal macrophages were strongly positive for
      Jagged1 staining. In contrast, macrophages separated from spleen and dendritic
      cells (DCs) separated from spleen and thymus showed positive staining for all the
      three ligands at a similar intensity. An analysis by RT-PCR revealed that
      peritoneal and splenic macrophages and splenic and thymic DCs, show a distinct
      pattern in Notch ligand expression. These findings may represent that expression
      of various Notch ligands in APCs has a physiological relevance in each organ.

PMID- 11841847
TI  - Enhanced T cells interactions with extracellular matrix proteins in infertile
      women with endometriosis.
AB  - Essential features of endometriosis involve interactions with extracellular
      matrix (ECM). Recent data emphasize the important role of ECM proteins in the
      regulation of T cell function. The aim of this study was to determine activated T
      cell adhesion to ECM proteins in infertile women with endometriosis. Nine women
      with endometriosis diagnosed by laparoscopy according to the Revised American
      Fertility Society classification and ten normal healthy women with a previous
      successful pregnancy outcome were studied. We investigated phorbol acetate
      myristate (PMA) or phytohemaglutinin (PHA) activated peripheral blood T cell
      adhesion to the following proteins of ECM: collagen IV (C-IV), elastin (E) and
      fibronectin (Fn). In addition, CD4, CD8, CD29, CD45RO expression on peripheral
      CD3(+) T cells were studied using flow cytometry. We determine that PHA-activated
      T cell adhesion to C-IV and Fn are significantly higher in infertile women with
      endometriosis when compared to normal healthy women (P<0.05). No significant
      differences were noted in T cell's surface antigens expression between study
      groups. Our data suggest the existence of disturbed T cell-ECM interactions in
      infertile women with endometriosis. Further studies are needed to determine the
      role of these abnormalities in the pathogenesis of endometriosis.

PMID- 11841848
TI  - Toll-like receptor 4 surface expression on human monocytes and B cells is
      modulated by IL-2 and IL-4.
AB  - Human Toll-like receptor 4 (TLR4) has recently been identified, and it has been
      shown to be the main protein involved in recognizing gram-negative bacteria. We
      examined the regulation of TLR4 surface expression in human peripheral blood
      monocytes and B cells by interleukin-2 (IL-2) and IL-4. IL-2 up-regulated TLR4
      surface expression on human peripheral blood monocytes, but did not change
      expression on human peripheral B cells. By contrast, IL-4 down-regulated TLR4
      surface expression on human peripheral blood monocytes, but up-regulated TLR4
      surface expression on human peripheral B cells. These results indicate that Th1
      cytokine IL-2 enhances receptors involved in the response to gram-negative
      bacteria and that activation of cellular immunity may enhance defense against
      these pathogens through monocytes, but not B cells, whereas Th2 cytokine IL-4
      modulates the receptor response to gram-negative bacteria and that activation of
      humoral immunity may enhance defense against these pathogens through B cells, but
      not monocytes.

PMID- 11841849
TI  - In vivo cytokine responses in gut-associated lymphoid tissue (GALT) and spleen
      following oral administration of staphylococcal enterotoxin B.
AB  - The mechanisms responsible for oral tolerance have been analyzed using various
      antigens. The induction of oral nonresponsiveness to low doses of Staphylococcal
      Enterotoxin B (SEB), in which SEB-reactive clonal anergy and deletion are
      involved, has also been confirmed. However, few reports have examined the
      cytokine milieu of the mucosal and peripheral lymphoid tissue during tolerance
      induction after the oral administration of SEB. In this study, to elucidate the
      mechanism responsible for the oral tolerance to low dose of SEB, the cytokine
      responses of the gut-associated lymphoid tissues (GALT) and the spleen were
      examined using the reverse transcription-polymerase chain reaction (RT-PCR)
      method. After the oral administration of a single low dose of SEB, the
      expressions of Th2 and TGF-beta, and to a lesser extent Th1 mRNA were observed in
      the mucosa. In contrast, following repeated oral low doses of SEB, in a manner
      different from previous results using conventional antigens, no cytokine
      enhancements were demonstrated in the GALT or the spleen. In conclusion, the
      involvement of unknown inhibitory or regulatory cytokines, together with SEB
      reactive clonal anergy and deletion, is suggested in the induction of oral
      tolerance to low dose SEB.

PMID- 11841850
TI  - Human endogenous retrovirus IDDMK(1,2)22 and mouse mammary tumor virus
      superantigens differ in their ability to stimulate murine T cell hybridomas.
AB  - Recently, a newly identified human HERV-K18 like endogenous retrovirus
      (IDDMK(1,2)22) has been associated to the etiology of type I diabetes (IDDM).
      Although the exact mechanism remains unclear, it was postulated that the 3' end
      ORF product of the env gene of IDDMK(1,2)22 would trigger a V beta 7-specific
      human T cell expansion leading to their infiltration in the pancreas of afflicted
      patients and to the autoimmune destruction of the insulin-producing beta cells.
      Since then, such superantigen (SAg)-like activity as well as the association
      between the IDDMK(1,2)22 virus and IDDM pathogenesis have been challenged. To
      further characterize functionally the putative IDDMK(1,2)22-encoded SAg, we have
      cloned from human DNA the identical 462bp ORF sequence originally described. The
      IDDMK(1,2)22 ORF fragment was transfected in the same human B cell line (Raji)
      originally used as APC to demonstrate the V beta 7 specificity. The
      immunostimulatory potential of IDDM ORF was tested on murine T cell hybridomas
      and compared to the well-characterized mouse mammary tumor virus Mtv7 SAg
      transfected in the same conditions. A panel of 16 T cell hybridomas encompassing
      14 different V betas was analyzed. We have failed to detect IDDMK(1,2)22-induced
      IL-2 production from any of these hybridomas, even those bearing the murine V
      beta 1 mV beta 1, V beta 4 or V beta 10 TcR beta chains which are most closely
      related to the human V beta 7 (hV beta 7). Our results suggest that IDDMK(1,2)22
      ORF is devoid of superantigenic activity as defined by classical criteria.

PMID- 11841851
TI  - Centromere round-up at the heterochromatin corral.

PMID- 11841852
TI  - Gene targeting comes to top-down drug screens.

PMID- 11841857
TI  - Anthrax-related panic is more dangerous than the disease.

PMID- 11841858
TI  - Tackling the bottleneck of protein crystallization in the post-genomic era.

PMID- 11841859
TI  - Membrane anchors for vacuolar targeting: application in plant bioreactors.
AB  - Transgenic plants are attractive expression systems for producing recombinant
      proteins. Plant cells compartmentalize and store metabolites and proteins in
      vacuoles, but foreign proteins need to be targeted to the correct compartments if
      they are to accumulate in a stable fashion. Here we present a general strategy in
      which unique transmembrane and cytoplasmic tail sequences are used as anchors for
      delivering recombinant proteins via distinct vesicular transport pathways to
      specific vacuolar compartments where stable accumulation can occur.

PMID- 11841860
TI  - Optimizing scale-up fermentation processes.
AB  - There are many aims associated with the optimization of fermentation processes.
      Optimization is expected to increase the yield of the final product but the
      process must be compliant with good manufacturing practices, the available
      equipment and the expected final scale of operation. Dealing with genetically
      modified microorganisms that overproduce recombinant protein has the advantage
      that the vast majority of the processes use only three different species, namely
      Escherichia coli, Saccharomyces cerevisiae and Pichia pastoris. Standard
      processes for each organism are described in textbooks and serve as a basis for
      the development of a tailored process. This article outlines the general
      philosophy that we have devised to ensure an efficient approach of scaling up
      fermentation processes for biopharmaceutical purposes, in a multidisciplinary
      environment.

PMID- 11841861
TI  - Using technology to address recruitment issues in the clinical trial process.
AB  - It takes nearly ten years to get a drug through the discovery and development
      pipeline and onto the market; most of this time is spent in the clinical phase.
      Clinical development times vary widely from drug to drug, but a drug typically
      spends just over 6 years going through clinical trials and regulatory processes.
      At least 3 years of this time is spent recruiting patients. Every month by which
      the development process can be shortened is worth US $25 million in additional
      income for the average drug. Can the recruitment time be shortened?

PMID- 11841862
TI  - Functional cell-based uHTS in chemical genomic drug discovery.
AB  - The availability of genomic information significantly increases the number of
      potential targets available for drug discovery, although the function of many
      targets and their relationship to disease is unknown. In a chemical genomic
      research approach, ultra-high throughput screening (uHTS) of genomic targets
      takes place early in the drug discovery process, before target validation. Target
      selective modulators then provide drug leads and pharmacological research tools
      to validate target function. Effective implementation of a chemical genomic
      strategy requires assays that can perform uHTS for large numbers of genomic
      targets. Cell-based functional assays are capable of the uHTS throughput required
      for chemical genomic research, and their functional nature provides distinct
      advantages over ligand-binding assays in the identification of target-selective
      modulators.

PMID- 11841863
TI  - Microfabricated devices in biotechnology and biochemical processing.
AB  - In the past few years, interdisciplinary science and technologies have converged
      to create exciting challenges and opportunities, which involve a new generation
      of integrated microfabricated devices. These new devices are referred to as 'lab
      on-a-chip' or Micro Total Analysis Systems. Their development involves both
      established and evolving technologies, which include microlithography,
      micromachining, Micro Electro Mechanical Systems technology, microfluidics and
      nanotechnology. This review summarizes the key device subject areas and the basic
      interdisciplinary technologies, and gives a better understanding of how these
      technologies can be used to provide appropriate technical solutions to
      fundamental problems. Important applications for this novel 'synergized'
      technology in chemical and biotechnological processing, in addition to the
      application of simulation methods in the development of microfabricated devices,
      will also be discussed.

PMID- 11841864
TI  - Artificial cells: prospects for biotechnology.
AB  - A variety of techniques can now be used to alter the genome of a cell. Although
      these techniques are very powerful, they have limitations related to cost and
      efficiency of scale. Artificial cells designed for specific applications combine
      properties of biological systems such as nanoscale efficiency, self-organization
      and adaptability at relatively low cost. Individual components needed for such
      structures have already been developed, and now the main challenge is to
      integrate them in functional microscopic compartments. It will then become
      possible to design and construct communities of artificial cells that can perform
      different tasks related to therapeutic and diagnostic applications.

PMID- 11841865
TI  - A shrewd and ethical approach to xenotransplantation.
AB  - Policies surrounding xenotransplantation, and many other emerging high-technology
      interventions, must balance opportunity and risk. Whereas traditional
      stakeholders, such as the researcher community, government agencies and the
      commercial sector, readily contribute to the debates that influence policies, the
      voice of the public is seldom heard. Not only does this raise ethical concerns
      but also it might ultimately prove to be shortsighted. Before any country settles
      unilaterally on comprehensive policies governing the practice of
      xenotransplantation, well-informed public opinions need to be taken into account.

PMID- 11841870
TI  - Pyrrolo[1,2-f]phenanthridines and related non-rigid analogues as antiviral
      agents.
AB  - The pyrrolo[1,2-f]phenanthridines 8-22 and the corresponding non-rigid analogues
      23-41 were synthesised and their ability to inhibit the replication of HIV-1 was
      tested. Only the polycyclic derivatives 10, 11, and 13 showed a weak anti-HIV
      activity, whereas several pyrrolo-phenanthridines (8, 10, 16-18) were found to
      stimulate the multiplication of MT-4 cells at low concentrations. Derivative 10
      demonstrated to possess the unique property of stimulating the multiplication of
      lymphocytes joined to HIV inhibition.

PMID- 11841871
TI  - Conformationally restrained analogues of sympathomimetic catecholamines.
      Synthesis and adrenergic activity of 5,6- and 6,7-dihydroxy-3,4
      dihydrospiro[naphthalen-1(2H)-2',5'-morpholines].
AB  - The 5,6- (10a) and 6,7-dihydroxy-3,4-dihydrospiro[naphthalen-1(2H)-)-2',5'
      morpholine](11a) and their N-isopropyl derivatives (10b and 11b) (DDSNMs), which
      can be viewed as the result of the combination of the structure of the 2-(3,4
      dihydroxyphenyl)morpholine 5a or 5b (DPMs) with the structure of the
      corresponding 1-(aminomethyl)-5,6-dihydroxy- (8a or 8b) or 1-(aminomethyl)-6,7
      dihydroxy-1,2,3,4-tetrahydro-1-naphthalen-ol (9a or 9b) (1-AMDTNs) were
      synthesised. The new compounds DDSNMs 10a,b and 11a,b were assayed for their
      alpha- and beta-adrenergic properties by means of binding experiments and
      functional tests and the results were compared with those obtained for
      catecholamines 1a, b and the previously described morpholine (5) and
      tetrahydronaphthalene (8, 9) derivatives. The affinity and activity indices thus
      obtained indicate in general a low ability of the new compounds 10 and 11 to
      interact with the alpha- and beta-adrenoceptors, which, in all cases, was lower
      than that of the corresponding morpholine (5) and tetrahydronaphthalene (8, 9)
      analogues.

PMID- 11841872
TI  - Identification, synthesis and pharmacological activity of moxonidine metabolites.
AB  - The metabolism of moxonidine, 4-chloro-N-(4,5-dihydro-1H-imidazol-2-yl)-6-methoxy
      2-methyl-5-pyrimidinamine, LY326869, in rats, mice, dogs, and humans has been
      examined. At least 17 metabolites were identified or tentatively identified in
      the different species by HPLC, LC/MS and LC/MS/MS. The identities of seven of the
      major metabolites have been verified by independent synthesis. The metabolites
      are generally derived from oxidation and conjugation pathways. Oxidation occurred
      at the imidazolidine ring as well as the methyl at the 2 position of the
      pyrimidine ring. All seven metabolites were examined in the spontaneously
      hypertensive rats (3 mg kg(-1), i.v.) for pressure and heart rate. Only one, 2
      hydroxymethyl-4-chloro-5-(imidazolidin-2-ylidenimino)-6-methoxypyrimidine,
      exerted a short-lasting decrease in blood pressure, albeit attenuated in
      magnitude compared to moxonidine.

PMID- 11841874
TI  - Design and synthesis of a series of indole glycoprotein IIb/IIIa inhibitors.
AB  - Synthesis of 1,3-disubstituted indoles derivatives as potential glycoprotein (GP)
      IIb/IIIa antagonists was reported. Substitution of the indolic nitrogen atom by
      piperidino or benzamidino moieties was used as mimics of an arginine residue. The
      acid carboxylic group was linked to the indole scaffold in position-3 via a
      methylene unit (compounds 4, 9, 10). Introduction of a beta-alanine chain was
      carried out on the acids (17-22) which after deprotection and basic hydrolysis
      afforded the final compounds 39-46. The distance between the indole scaffold and
      the amide bond was modulated from no methylene unit (compound 39) to 1 (compounds
      40, 41) or 2 methylene units (compounds 42-46). The presence of a tosylamino
      group on the beta-alanine chain (compound 56) slightly increased the inhibiting
      action on platelet aggregation initiated by collagen.

PMID- 11841873
TI  - Cytotoxic 1,4-bis(2-oxo-1-cycloalkylmethylene)benzenes and related compounds.
AB  - A series of 1,4-bis(2-oxo-1-cycloalkylmethylene)benzenes 2a-c and 4 and a related
      acyclic analogue 6a were synthesised and converted to the corresponding Mannich
      bases 3a-c, 5 and 6b. Evaluation of these compounds against murine P388 and L1210
      cells as well as human Molt 4/C8 and CEM T-lymphocytes revealed that the Mannich
      bases were more cytotoxic than the corresponding unsaturated ketones. 1,4-bis(3
      Dimethylaminomethyl-2-oxo-1-cyclohexylmethylene)benzene dihydrochloride (3a) had
      lower IC(50) values than melphalan against the four cell lines and was 15 times
      more potent than this drug when examined against a panel of human tumours.

PMID- 11841875
TI  - Bifunctional derivative of p,p'-dichlorochalcone. Part III. Synthesis and study
      for cytotoxic activity of a new compound, 2-[2,2-bis(4-chlorophenyl)ethyl]-2-(4
      chlorophenyl)-thiazolidin-4-one from p,p'-dichlorochalcone.
AB  - The synthesis of 2-(2,2-bis(4-chlorophenyl)ethyl]-2-(4-chlorophenyl)-thiazolidin
      4-one (3) from p,p'-dichlorochalcone (1) via 1,3,3-tris(4-chlorophenyl)-propan-1
      one (2) using thioglycollic acid in the presence of ammonium carbonate is
      described. Structural assignment, stereochemistry and biological assay are
      discussed.

PMID- 11841876
TI  - Synthesis and vasorelaxant activity of 4-(cyclic amido)-2H-naphtho[1,2-b]pyrans.
AB  - A series of 4-(cyclic amido)-2H-naphtho[1,2-b]pyrans related to cromakalim (1)
      has been prepared and their vasorelaxant activities on isolated rat thoracic
      aorta precontracted with phenylephrine have been evaluated. The relaxant
      mechanism of 3a was found not through ATP-sensitive K(+) channels as cromakalim,
      but through opening voltage-sensitive K(+) channels.

PMID- 11841877
TI  - 6-Arylamino-5,8-quinazolinediones as potent inhibitors of endothelium-dependent
      vasorelaxation.
AB  - 6-(Substituted-phenyl)amino-5,8-quinazolinediones (3) were synthesised by
      regioselective substitution of 5,8-quinazolinedione (5) with appropriate
      arylamines in the presence of Ce(III) ions. All synthesised 5,8-quinazolinediones
      3 showed a potent and efficacious inhibitory effect on the acetylcholine (ACh)
      induced vasorelaxation of rat aorta with the endothelium. The quinones 3, at a
      low concentration of 0.1 microM, reduced the maximal response with increase of
      EC(50) values for ACh. The results indicate that quinones 3 are potent inhibitors
      of endothelium-dependent vasorelaxation.

PMID- 11841878
TI  - 2-Arylalkyl-substituted anthracenones as inhibitors of 12-lipoxygenase enzymes.
      2. Structure-activity relationships of the linker chain.
AB  - A series of 2-arylalkyl-substituted anthracenones were tested as inhibitors of
      three types of 12-lipoxygenase isoforms in epidermal homogenate of mice, bovine
      platelets and porcine leukocytes. Their inhibitory activities were compared with
      those to inhibit the 5-lipoxygenase enzyme in bovine leukocytes. The compounds
      were synthesised by Marschalk, Wittig or Horner-Emmons reaction at the
      anthracenedione stage and then reduced to the anthracenones. Structure-activity
      relationship for the chain linking the anthracenone nucleus and the phenyl ring
      terminus was investigated. The 2-phenylethyl analogues were among the most potent
      inhibitors, and 3,4-dimethoxy-substituted 10f was identified as a selective
      inhibitor of the 12-LO enzymes over 5-LO. Selectivity for 12-LO isoforms was
      observed with an increase in the overall lipophilicity of the inhibitors.
      However, none of the linker chains of the 2-substituted anthracenones provided
      inhibitors that were able to discriminate between the 12-LO isoforms.

PMID- 11841880
TI  - L-selectin in health and disease.
AB  - This article reviews recent advances in the knowledge of the role of L-selectin,
      an adhesion molecule that is expressed on the surface of circulating leucocytes,
      in animal and human physiology and pathophysiology. After a brief discussion on
      nomenclature and structure, it progresses through the evidence for expression and
      regulation of L-selectin, cell collection and purification, physiological
      function and roles. The special role of knock out mice and monoclonal antibodies
      in determining a role for L-selectin in inflammatory states is described before
      proceeding to discuss the importance of L-selectin ligands and shed L-selectin. A
      second section describes a role for L-selectin in pathophysiological states in
      animals and man, with special reference to trauma, systemic inflammatory
      syndromes and sepsis. The review concludes with a summary of the potential role
      of anti-inflammatory medication and L-selectin blockers in the management of
      inflammation.

PMID- 11841881
TI  - Defibrillation by general practitioners.
AB  - OBJECTIVE: To investigate the mode of cardiac arrest in patients with acute
      myocardial infarction attended by general practitioners, and the effectiveness of
      early defibrillation. DESIGN: Retrospective observational study. SETTING: British
      general practice. PARTICIPANTS: General practitioners equipped with
      defibrillators by the British Heart Foundation. MAIN OUTCOME MEASURES: Cardiac
      rhythm when first monitored, response to defibrillation assessed by survival to
      reach hospital alive and survival to hospital discharge. INTERVENTIONS:
      Defibrillation and standard cardiopulmonary resuscitation in patients with
      cardiac arrest complicating acute myocardial infarction attended by British
      general practitioners. RESULTS: When a doctor equipped with a defibrillator
      witnessed an arrest or was able to initiate resuscitation within 4 min of the
      patient collapsing, 90% of patients were found to have developed a rhythm likely
      to respond to a defibrillatory shock. Defibrillation under these circumstances
      was very successful with more than 70% of patients subsequently admitted to
      hospital alive and approximately 60% surviving to be discharged alive. When the
      doctor commenced resuscitation later, fewer patients were found to have rhythms
      likely to be responsive to a DC shock. A greater proportion was in asystole and
      resuscitation was less frequently successful under these circumstances. When the
      arrest occurred in the doctor's surgery, 85% of patients were admitted to
      hospital alive and three quarters survived to hospital discharge. CONCLUSIONS:
      All those who provide the initial care for this vulnerable group of patients
      should be equipped with defibrillators. The more widespread deployment of
      defibrillators in the community may be a successful strategy for reducing
      unnecessary deaths from coronary heart disease.

PMID- 11841882
TI  - Beneficial effects of vasopressin in prolonged pediatric cardiac arrest: a case
      series.
AB  - Children who suffer cardiac arrest have a poor prognosis. Based on laboratory
      animal studies and clinical data in adults, vasopressin is an exciting new
      vasopressor treatment modality during cardiopulmonary resuscitation (CPR). In
      particular, vasopressin has resulted in short term resuscitation benefits as a
      "rescue" pressor agent in the setting of prolonged out-of-hospital CPR for
      ventricular fibrillation in adults. This retrospective series presents the first
      evidence for resuscitation benefit of bolus vasopressin therapy in the specific
      setting of pediatric cardiac arrest. All episodes of CPR initiated in a 120-bed
      tertiary care children's hospital over a three-year period (1997-2000) were
      reviewed. Four children in the pediatric ICU received vasopressin boluses as
      rescue therapy during six cardiac arrest events, following failure of
      conventional CPR, advanced life support, and epinephrine vasopressor therapy.
      Return of spontaneous circulation for greater than 60 min occurred in three of
      four patients (75%) and in four of six CPR events (66%) following vasopressin
      administration. Two of four vasopressin recipients survived >24 h; one survived
      to hospital discharge and one had withdrawal of supportive therapies following
      family discussion. Our observations are AHA level 5 (retrospective case series)
      evidence that vasopressin administration may be beneficial during prolonged
      pediatric cardiac arrest. Such reports should pave the way for prospective
      clinical trials comparing vasopressor medications in the setting of pediatric
      cardiac arrest.

PMID- 11841883
TI  - Feasibility of external cranial cooling during out-of-hospital cardiac arrest.
AB  - Hypothermia during brain ischemia can improve neurological outcome. This study
      tested whether local cranial cooling during the low-flow state of cardiopulmonary
      resuscitation (CPR) could produce clinically significant cerebral cooling. Ice
      was applied to the heads and necks of subjects (hypothermia group) with out-of
      hospital cardiac arrest (OOHCA) during CPR. Nasopharyngeal and tympanic
      temperatures were measured as surrogates for cerebral temperature. The rate of
      cranial cooling in the hypothermia group (-0.06 +/- 0.06 degrees C/min) was not
      significantly increased compared with a control group without ice (-0.04 +/- 0.07
      degrees C/min), although older age was associated with more rapid cranial
      cooling. Of note, many subjects with OOHCA are already mildly hypothermic (mean
      cranial temperature= 35.0 +/- 1.2 degrees C) when they are first encountered in
      the field. This study suggests that brief cranial cooling is ineffective for
      rapidly lowering brain temperature. However, most cardiac arrest victims are
      spontaneously mildly hypothermic and preventing rewarming may provide some of the
      desired benefits of cerebral hypothermia.

PMID- 11841884
TI  - Slow-infusion of calcium channel blockers in the emergency management of
      supraventricular tachycardia.
AB  - OBJECTIVE: To compare the efficacy of verapamil and diltiazem as slow infusions
      in terminating spontaneous supraventricular tachycardia (SVT) in the emergency
      department (ED). METHOD: Patients of at least 10 years of age who presented to
      our ED with regular narrow complex tachycardia not converted with a vagal
      manoeuvre with an ECG diagnosis of SVT were included. Those who were
      haemodynamically unstable were excluded. Patients were randomized to undergo
      either verapamil infusion at a rate of 1 mg/min to a maximum of 20 mg or
      diltiazem infusion at a rate of 2.5 mg/min to a maximum of 50 mg. RESULTS: Eighty
      one patients were randomized to receive verapamil infusion and 80 were randomized
      to receive the diltiazem infusion. There is no difference in success rate between
      verapamil (98.8%) and diltiazem (96.3%) infusion. The dose of medication required
      to convert 25,50 and 75% of SVTs were 4.0,5.0 and 8.0 mg for the verapamil
      infusion and 10.0,12.5 and 17.5 mg for the diltiazem infusion. There was one
      complication in each group. CONCLUSION: Calcium channel blockers infusions were
      safe and efficacious in terminating spontaneous SVT. There was no difference
      between the success rates of verapamil and diltiazem infusions.

PMID- 11841885
TI  - Calcium channel blockers as first line treatment for broad complex tachycardia
      with right bundle branch block: ingenuity or folly?
AB  - OBJECTIVE: To study the response of regular broad-complex tachycardia (BCT)
      demonstrating right bundle branch block (RBBB) to treatment in the Emergency
      department (ED). METHODS: Retrospective chart review of management of patients
      with BCT, RBBB without a history of ischaemic heart disease. A diagnosis of
      ventricular tachycardia (VT) was made if the ECG showed features such as
      atrioventricular dissociation, capture or fusion beats or if VT was demonstrated
      during electrophysiological studies (EPS). RESULTS: A total of 25 patients were
      eligible. Nineteen patients were given intravenous (IV) calcium channel blockers
      (either verapamil or diltiazem), as first line treatment. Of these, 18 converted
      to sinus rhythm and the other one patient subsequently converted with amiodarone.
      The remaining six patients were given IV adenosine (n=3), lignocaine (n=2) or
      amiodarone (n=1) as first line treatment but none of them were converted. Of
      these, four of them converted with IV calcium channel blockers eventually. Of the
      other two patients, who were both given lignocaine initially, one deteriorated
      haemodynamically with the use of verapamil and required synchronised
      cardioversion to convert. The other patient did not respond to amiodarone and
      synchronised cardioversion but was subsequently converted with verapamil. The
      difference between the success rate of calcium channel blockers and other anti
      arrhythmics is statistically significant (P<0.01 by Fischer's exact method).
      Fourteen cases had diagnoses of VT, including the two patients given lignocaine.
      Five cases were found to have supraventricular tachycardia with aberrant
      conduction. Six cases did not have confirmed diagnoses. CONCLUSION: In patients
      presenting with BCT and RBBB but without underlying ischaemic heart disease,
      there is evidence to suggest that calcium channel blockers could effectively be
      used as the treatment of choice.

PMID- 11841886
TI  - The use of the laryngeal mask airway and Combitube in cardiopulmonary
      resuscitation; a national survey.
AB  - The laryngeal mask airway (LMA) and Combitube have been recommended for use
      during cardiopulmonary resuscitation (CPR). An overview of current practice was
      sought by conducting a postal survey of 265 Resuscitation Training Departments,
      at different hospitals, throughout the UK. One hundred fifty-three (58%)
      completed questionnaires were returned. Only 38 (25%) hospitals which replied
      were currently using the LMA in resuscitation while seven (5%) were using the
      Combitube. The reasons for not using these airway adjuvants included concerns
      about airway protection, difficulties in training, cost, and the concept that
      when anaesthetists were available on cardiac arrest teams these devices were
      unnecessary.

PMID- 11841887
TI  - Pre-hospital care--the evolution of a course for undergraduates.
AB  - Newly qualified doctors are ill equipped to deal with pre-hospital trauma
      emergencies. There is a public perception that medical education provides both
      experience and knowledge in this field. In Birmingham, United Kingdom (UK),
      committed doctors and nurses trained in pre-hospital care have evolved a specific
      course designed to equip the medical undergraduate to deal with pre-hospital
      trauma scenario. The pre-hospital trauma course for medical students has run
      annually from 1993 to 2000. The course caters for 200 students with a faculty of
      30 instructors. Successful completion of the course which is rigorously assessed
      grants a certificate awarded by the Faculty of Pre-hospital Care at the Royal
      College of Surgeons of Edinburgh. Most importantly it equips the undergraduate
      with essential theoretical knowledge and practical skills to handle a pre
      hospital trauma emergency.

PMID- 11841888
TI  - Extending the golden hour of hemorrhagic shock tolerance with oxygen plus
      hypothermia in awake rats. An exploratory study.
AB  - In a previous study of volume-controlled hemorrhagic shock (HS) in awake rats,
      without fluid resuscitation, either breathing of 100% oxygen or moderate
      hypothermia while breathing air, increased survival time. We hypothesized that
      combining oxygen and hypothermia can maximally extend the "golden hour" of HS
      from which resuscitation can be successful in terms of survival rate. Rats were
      prepared under light general anesthesia, breathing spontaneously via face mask,
      and then awakened for 2 h. Then, 3.25 ml arterial blood/100 g were withdrawn over
      20 min. At the end of HS of 30, 60, 90 or 180 min duration, the shed blood was
      reinfused. Breathing was spontaneous. Survival endpoint was 24 h or earlier
      death. HS of 30 or 60 min was used for preliminary experiments; HS of 90 or 180
      min for 35 definitive experiments. Control groups A-1 and B-1 had normothermia
      (rectal temperature 37.5 degrees C) and were breathing air. Treatment groups A-2
      and B-2 had total body surface cooling during HS to rectal temperature 32 degrees
      C and were breathing 100% O(2). Arterial pressure during HS was higher in the
      hypothermia-O(2) groups. With HS of 90 min, in the normothermia-air group A-1
      (n=10), none of the 10 rats survived to 3 h; while in the hypothermia-O(2) group
      A-2 (n=5), all rats survived to 24 h (P<0.001). With HS of 180 min, in the
      normothermia-air group B-1 (n=10), three of 10 rats survived to 3 h and 24 h
      (hypotension during HS in these three survivors was less severe than in the non
      survivors); and in the hypothermia-O(2) group B-2 (n=10) all 10 rats survived to
      24 h (P<0.003). We conclude that moderate hypothermia (32 degrees C) plus 100%
      oxygen inhalation during volume-controlled HS in awake rats mitigates hypotension
      and increases the chance of survival. It enables survival even after 3 h of
      moderate HS.

PMID- 11841889
TI  - Synaptosomal susceptibility on global ischaemia caused by cardiac arrest
      correlated with early and late times after recirculation in rats.
AB  - The aim of the study was to assess the sensitivity of brain synaptosomes and
      their mitochondria to the effects of global cerebral ischaemia caused by
      temporary cardiac arrest and the early and late consequences. The effects of 10
      min of global ischaemia were measured immediately and after 1 h, 24 h and 7 days
      post-resuscitation. Ischaemia caused a reduction in oxygen consumption by
      synaptosomes of about 20%, a drop in ATP/ADP ratio of about 40%, a decrease in
      CrP/Cr ratio at about 45% and a reduction of synaptic vesicles and disturbances
      in the mitochondrial structure in isolated synaptosomes and in nerve endings of
      brain specimens. Morphometric analysis showed that ischaemic conditions caused a
      decrease in synaptic vesicles by about 61% and an increase of mitochondrial
      damage to 58 and 50% after 1 and 24 h postreperfusion time, respectively. Seven
      days postresuscitation, all the observed changes returned to normal but small
      numbers (about 2%) of neurones which were destroyed neurons appeared at that
      time. It is concluded that global ischaemia with early resuscitation after
      cardiac arrest may lead to damage of synaptosomes and synaptic mitochondria.
      This, in turn, modifies substrate oxidation, synthesis of energy variables and
      affects neurotransmitter function. The observed disturbances return to normal
      later after resuscitation but the ischaemic events and reoxygenation caused
      selective morphological injury of certain neurones and this may form the basis
      for irreversible brain damage.

PMID- 11841890
TI  - Vasopressin and epinephrine are equally effective for CPR in a rat asphyxia
      model.
AB  - Epinephrine has been administered as a drug essential for cardiopulmonary
      resuscitation (CPR). Recently, vasopressin has been reported to be more effective
      than epinephrine for CPR in a ventricular fibrillation (VF) model. As a different
      myocardial pathology is speculated to exist between the VF model and the asphyxia
      model, we investigated whether vasopressin is also effective in a rat asphyxia
      model. Twenty-one Sprague-Dawley male rats were divided into three groups:
      vasopressin 0.8 U/kg (Vaso-Gr), epinephrine 0.05 mg/kg (Epi-Gr), and saline same
      volume as the other two drugs (Sal-Gr). Five minutes after suffocation induced by
      obstruction of the tracheal tube, CPR was performed using each drug. Although
      only one animal survived (17%) in the Sal-Gr, 6/7 (85%) survived in both Vaso-Gr
      and Epi-Gr (P<0.01). Vasopressin is as effective as epinephrine for CPR in
      asphyxia-induced rats.

PMID- 11841891
TI  - Use of the laryngeal tube for out-of-hospital resuscitation.
AB  - Every physician involved in emergency medicine should be familiar with
      alternative techniques for managing the difficult airway. We report a case of a
      patient who was successfully ventilated and oxygenated with a laryngeal tube,
      when tracheal intubation failed. Ventilation was possible even during continuous
      chest compressions. Airway equipment, including one supraglottic alternative for
      patients of all ages and a set for cricothyroidotomy, for those experienced in
      its use, should be available on every ambulance equipped for advanced life
      support.

PMID- 11841892
TI  - GABA(B) receptor agonists for the treatment of drug addiction: a review of recent
      findings.
AB  - A growing preclinical and clinical literature suggests that GABA(B) receptor
      agonists promote abstinence and reduce the use of cocaine, heroin, alcohol and
      nicotine. The purpose of this paper is to critically review these data. GABA(B)
      receptor agonists, such as baclofen, appear to reduce the reinforcing effects of
      abused drugs in animal models under multiple experimental procedures. This occurs
      at doses that have little effect on responding for other positive reinforcers
      such as food or water. We review evidence that these potential therapeutic
      effects may be mediated by modulation of mesolimbic dopamine neurons. This review
      also examines the preliminary clinical data from studies of the efficacy of
      baclofen for treatment of cocaine, alcohol, and nicotine dependence. We suggest
      that these preliminary data provide a rationale for conducting more systematic
      studies of the effects of GABA(B) receptor agonists as treatment for drug abuse.
      This line of research may also improve our understanding of the neurochemical
      mechanisms underlying the drug dependence process.

PMID- 11841893
TI  - Association of a CB1 cannabinoid receptor gene (CNR1) polymorphism with severe
      alcohol dependence.
AB  - Due to the involvement of the endogenous cannabinoid system in brain reward
      mechanisms a silent polymorphism (1359G/A; Thr453Thr) in the single coding exon
      of the CB1 human cannabinoid receptor gene (CNR1) was analysed in 121 severely
      affected Caucasian alcoholics and 136 most likely non-alcoholic controls. The
      observed frequency of the A allele was 31.2% for controls and 42.1% for
      alcoholics with severe withdrawal syndromes (P=0.010). Post-hoc exploration
      indicated that this allelic association resulted from an excess of the homozygous
      A/A genotype in patients with a history of alcohol delirium (P=0.031, DF 2),
      suggesting s an increased risk of delirium (OR=2.45, 95% CI 1.14--5.25). This
      finding suggests that the homozygous genotype CNR1 1359A/A confers vulnerability
      to alcohol withdrawal delirium.

PMID- 11841895
TI  - Heavy cannabis use among UK teenagers: an exploration.
AB  - Findings are presented from a survey of a sample of 2641 UK school students aged
      15--16 years. This exercise was part of the 30 country European School Survey
      Project on Alcohol and other Drugs (ESPAD). The 201 students who reported using
      cannabis (marihuana) 40 times or more were examined using cluster analysis. They
      were also compared to other students. Three clusters of heavy cannabis users
      emerged. The smallest was largely distinguished by antisocial behaviour. Another
      cluster were clearly unhappy, with little support from parents and friends, high
      levels of depressed mood and low levels of self-esteem. The largest cluster were
      'ordinary' and had little to distinguish them apart from a belief that their
      environment was stable and predictable and that society's rules should be obeyed.
      Although clear relationships emerged between heavy cannabis use and heavy use of
      other substances, the 'ordinary' cluster of heavy cannabis users were less likely
      than the others to have used other illicit drugs. It is therefore concluded that
      teenage heavy cannabis users have varied motivations and contexts for their
      usage. They should not be seen as a homogeneous group and many do not appear to
      use other illicit drugs.

PMID- 11841894
TI  - Personality, drug of choice, and comorbid psychopathology among substance
      abusers.
AB  - The current study investigated the association between substance
      abuse/dependence, drug of choice, and the personality traits of negative
      emotionality, positive emotionality, and constraint (disinhibition) as measured
      by the Multidimensional Personality Questionnaire. The sample comprises 325
      subjects from the Yale Family Study, a family study investigating the relation
      between substance-use disorders and anxiety disorders and their transmission in
      families. A total of 205 (63%) met criteria for lifetime substance
      abuse/dependence, with the remainder comprising the comparison group. The
      substance abusers were placed into one of four predominant drug of
      abuse/dependence categories (opioid, cocaine or stimulants, marijuana or
      sedatives, or alcohol) based upon best-estimate diagnoses and one of five self
      reported drug of preference groups (polysubstance, opioid, cocaine or stimulants,
      marijuana or sedatives, and alcohol). First, findings demonstrate that
      individuals with substance abuse/dependence, compared to those without, scored
      lower on constraint even after adjusting for socio-demographic factors, comorbid
      psychiatric disorder, and current/remitted substance-use disorder. Individuals
      with substance abuse/dependence scored marginally higher on negative
      emotionality, but this difference was statistically significant only when
      comorbid psychopathology was not controlled. Second, findings show that
      individuals who differ with respect to drug of choice-whether defined in terms of
      the predominant drug of abuse/dependence or self-reported drug of preference-vary
      in terms of constraint. After controlling for socio-demographic indicators and
      comorbid psychopathology, scores on constraint generally decreased with the
      social deviance of the drug of choice, thereby underscoring a potentially
      important link between disinhibition and drug selection.

PMID- 11841896
TI  - Toluene inhalation produces regionally specific changes in extracellular
      dopamine.
AB  - The aim of the present study was to investigate the effect of toluene inhalation
      on dopaminergic transmission in two distinct brain areas presumably involved in
      mediating the reward processes important for toluene abuse. Extracellular
      dopamine (DA) levels were measured in prefrontal cortex (PFC) and nucleus
      accumbens (NACC) of freely moving rats using in vivo microdialysis. Inhalation of
      a behaviorally relevant concentration of toluene (3000 ppm) produced a
      significant increase in the PFC but not in the NACC. However, the odorant isoamyl
      acetate, increased PFC DA levels by only 37%, significantly less than the 96%
      increase observed following toluene exposure. When toluene inhalation was
      combined with cocaine administration (20 mg/kg i.p.), the response to the
      combined challenge was not different from the response to toluene alone in the
      PFC. However, the combination of these two drugs produced a supradditive response
      of 802% in the NACC, compared with the 450% increase observed following cocaine
      alone. Recent reports indicate that toluene influences the function of several
      ionotropic receptors in a subunit specific manner. As further evidence of
      specific effects, our results indicate regionally specific changes in
      dopaminergic transmission following toluene exposure.

PMID- 11841897
TI  - Conditioned suppression of behavior maintained by cocaine self-administration.
AB  - Shock-paired stimuli have produced conditioned suppression of behavior maintained
      by a variety of reinforcers such as food, water, sucrose, and intracranial self
      stimulation. With the ongoing pursuit of animal models for drug abuse treatment,
      it is surprising that this procedure for suppressing positively reinforced
      behavior has never been applied to drug-maintained behavior. The present study
      applied the conditioned suppression paradigm to behavior maintained by cocaine
      self-administration in rats. If shock-paired stimuli suppress ongoing cocaine
      self-administration, this would contrast with recent studies reporting that
      aversive stimuli can enhance the acquisition and reinstatement of behavior
      reinforced by cocaine. Rats were trained to bar-press for intravenous cocaine
      infusions on a variable-interval schedule. Then, a tone conditioned stimulus (CS)
      and a light CS were each paired with foot-shock while the rats were bar-pressing
      for cocaine. These CSs each came to reliably suppress responding in all subjects,
      just as shock-paired CSs suppressed responding by the positive reinforcers
      mentioned above. When the tone and the light were presented simultaneously in
      testing, suppression was significantly enhanced over that controlled by the
      single CSs. These results demonstrate that (1) cocaine-maintained behavior can be
      suppressed by environmental stimuli associated with non-drug reinforcers; and (2)
      combining stimuli that decrease drug self-administration can enhance their
      suppressive effects. Thus, the present findings can have implications for drug
      treatment.

PMID- 11841898
TI  - Effect of maternal methionine pre-treatment on alcohol-induced exencephaly and
      axial skeletal dysmorphogenesis in mouse fetuses.
AB  - Alcohol is known to induce folate deficiency and impair methionine synthase
      activity. Exogenous folic acid (FA) administered periconceptionally has been
      shown to prevent the first occurrence and recurrence of neural tube defects (NTD)
      in humans. Since folate, vitamin B(12) and methionine are metabolically
      interrelated, it was decided to determine the effect of methionine pre-treatment
      on alcohol-induced NTD and axial skeletal defects in mouse embryos. Following
      administration of a single dose of 70 or 150 mg/kg of methionine, 0.03 ml/g body
      weight of ethanol solution (25% v/v of absolute alcohol in saline) was injected
      intraperitoneally into pregnant mice at critical stages of neural tube
      development. The controls were either non-treated or saline treated and pair-fed
      and pair-watered. Fetuses were collected on gestation day 18. Alcohol and
      methionine plus alcohol numerically enhanced embryonic resorption and induced a
      significant reduction in fetal body weight. Alcohol alone caused a 3-fold
      increase in the background frequency of exencephaly in gestation days 7 and 8
      treatment groups. The low dose of methionine only numerically reduced the
      spontaneous exencephaly. Pre-treatment with methionine only produced a numerical
      but not statistically significant reduction in alcohol-induced exencephaly. The
      higher dose of methionine did not produce a particularly beneficial effect on
      embryonic survival, fetal body weight and occurrence of exencephaly. Alcohol
      induced cleft palate and limb malformations were ameliorated by methionine pre
      treatment. Craniofacial skeleton, vertebrae and ribs were extensively malformed
      both in the alcohol and methionine plus alcohol groups indicating a lack of
      rescue effects of methionine. Whereas supernumerary ribs and extra sternal ribs
      were augmented by methionine, occipitalization of the atlas vertebra was a
      malformation unique to the pre-treatment group. Plasma levels of several amino
      acids including that of methionine were significantly lowered by alcohol. Pre
      treatment with methionine produced a dose dependent enhancement of only
      methionine concentration. These data suggest that pre-administration of
      methionine only rescues mouse embryos of certain non-neural malformations and
      that the lack of ameliorative effect on NTD and axial skeletal defects may be due
      to the fact that alcohol lowers the concentration of a number of amino acids and
      therefore, supplementation should comprise a mixture of these amino acids and
      possibly FA and vitamin B(12).

PMID- 11841899
TI  - Retention rate and illicit opioid use during methadone maintenance interventions:
      a meta-analysis.
AB  - The efficacy of methadone maintenance in opioid addiction was assessed in terms
      of programme retention rate and reduction of illicit opioid use by means of a
      meta-analysis of randomised, controlled and double blind clinical trials. The
      results were compared with interventions using buprenorphine and levo
      acetylmethadol (LAAM). Trials were identified from the PubMed database from 1966
      to December 1999 using the major medical subject headings 'methadone' and
      'randomised controlled trial'. Data for a total of 1944 opioid-dependent patients
      from 13 studies were analysed. Sixty-four percent of patients received methadone,
      administered either as fixed or adjusted doses. Thus, 890 patients received > or
      = 50 mg/day (high dose group) and 392 were given < 50 mg/day (low dose group). Of
      662 controls, 131 received placebo, 350 buprenorphine (265 at doses > or = 8
      mg/day and 85 at doses < 8 mg/day) and 181 LAAM. High doses of methadone were
      more effective than low doses in the reduction of illicit opioid use (odds ratio
      [OR] 1.72, 95% confidence interval [CI] 1.26--2.36). High doses of methadone were
      significantly more effective than low doses of buprenorphine (< 8 mg/day) for
      retention rates and illicit opioid use, but similar to high doses of
      buprenorphine (> or = 8 mg/day) for both parameters. Patients treated with LAAM
      had more risk of failure of retention than those receiving high doses of
      methadone (OR 1.92, 95% CI 1.32--2.78). It is proposed that in agonist
      maintenance programmes, oral methadone at doses of 50 mg/day or higher is the
      drug of choice for opioid dependence.

PMID- 11841900
TI  - The effects of sponsorship in 12-step treatment of injection drug users.
AB  - What contributes to sustained abstinence from injection drug use by those who
      participate in community-based Narcotics Anonymous (NA) and Alcoholics Anonymous
      (AA) is not well understood. We know that sponsorship is a central element in
      these programs. To investigate the relationship between sponsorship and
      abstinence, we evaluated NA/AA sponsorship over a 1-year period in a longitudinal
      study of 500 former and current injection drug users in inner-city Baltimore
      recruited from the community-at-large, independent of treatment center
      affiliation. The findings indicated that having a sponsor in NA/AA for this
      population was not associated with any improvement in 1-year sustained abstinence
      rates than a non-sponsored group. However, being a sponsor over the same time
      period was strongly associated with substantial improvements in sustained
      abstinence rates for the sponsors, controlling for involvement with community
      organizations, NA/AA meeting attendance, marital status, employment,
      participation in drug and alcohol treatment centers and HIV status. Involvement
      in community organizations was also strongly associated with successful
      abstinence, controlling for the same variables. Of those participants involved
      with community organizations, more than half reported involvement in church
      activities. Our investigation suggests that, for NA/AA sponsors in this study
      population, providing direction and support to other addicts is associated with
      improved success in sustained abstinence for the sponsors but does little to
      improve the short-term success of the persons being sponsored.

PMID- 11841901
TI  - Pumping iron, risking infection? Exposure to hepatitis C, hepatitis B and HIV
      among anabolic-androgenic steroid injectors in Victoria, Australia.
AB  - AIMS: To measure exposure to the hepatitis C and B viruses and HIV among
      Victorian steroid injectors and evaluate associations between exposure and risk
      behaviour, and report other characteristics of the study group. DESIGN:
      Seroprevalence study using a convenience sample. SETTING: Victoria, Australia.
      PARTICIPANTS: Current injectors of illicit anabolic steroids. MEASUREMENTS:
      Prevalences of exposure to HIV and the hepatitis B and C viruses; associations of
      characteristics and behaviours with exposure; descriptive statistics for the
      sample. FINDINGS: Six of 63 blood samples (9.5%) contained hepatitis C virus
      antibodies; 12.0% tested positive for hepatitis B core antibody; none contained
      anti-HIV. Hepatitis C virus exposure was associated with heroin injection,
      imprisonment, sharing needles to inject other drugs, number of tattoos, and
      hepatitis B virus exposure. No significant differences existed in the steroid
      related risk behaviour of exposed and non-exposed individuals. Hepatitis B virus
      exposure was associated only with hepatitis C virus exposure, past imprisonment
      and age of first injection. CONCLUSIONS: Exposure to the hepatitis B and C
      viruses was detected; hepatitis C virus exposure was at much lower prevalence
      than normally found among other drug injectors. Factors other than steroid
      injecting were associated with exposure. Nonetheless, the hepatitis C-exposed
      reported many steroid-related and other risk behaviours which could spread the
      virus. Steroid injectors should not be neglected in blood-borne virus prevention
      efforts.

PMID- 11841902
TI  - Macromolecule absorption and cortisol secretion in newborn calves derived from in
      vitro produced embryos.
AB  - Earlier reports indicate that calves derived from in vitro produced (IVP) embryos
      are more susceptible to neonatal disease than calves produced after artificial
      insemination (AI) or natural mating. The aims of the present study were to
      investigate whether calves born after IVP embryos show an altered macromolecule
      absorption (immunoglobulin G (IgG) and porcine serum albumin (PSA)) compared with
      AI calves and whether the macromolecule absorption could be related to the degree
      of acidosis or to the cortisol secretion around birth. Hence, IgG and PSA
      absorption in control AI calves (n=7) was compared with that in two groups of IVP
      calves (IVP-defined: SOFaa embryo culture with polyvinyl alcohol, n=6; IVP-serum:
      SOFaa embryo culture with serum and co-culture, n=8). The calves were fed
      colostrum (40ml/kg) at 2, 6 and 12h after birth. At 24h after birth, both AI and
      IVP calves had achieved a level of plasma IgG sufficient to provide passive
      immunization (>15mg/ml). When the values were adjusted for the varying colostral
      IgG contents and the degree of acidosis, the IVP-defined calves had significantly
      lower peak plasma IgG concentrations than the AI calves at 18-24h after birth
      (P<0.04). However, when the macromolecule marker (PSA), was fed to all calves at
      2 and 12h after birth the resulting plasma PSA levels were significantly lower in
      the AI calves compared with the IVP calves during the whole observation period
      (P<0.0001). Calves with a moderate neonatal acidosis (mean pH<7.2 during the
      first 30min after birth) had reduced peak plasma IgG concentration at 18-24h
      after birth (P<0.02) compared to calves without acidosis. The basal and ACTH
      stimulated cortisol levels were lower in the newborn IVP-defined calves than in
      the AI calves (P<0.05) and the IVP-serum calves (P<0.002). Cortisol levels
      shortly after birth correlated positively with birth weight (r=0.60, P<0.0001)
      and with gestation length (r=0.34, P<0.04). Since, the IVP calves absorbed
      sufficient amounts of IgG from colostrum to acquire sufficient passive immunity,
      we conclude that the lower viability described in IVP offspring probably is not
      caused by an impaired passive immunization. IVP-defined calves had significantly
      lower absorption efficiency of IgG compared with AI calves, whereas absorption of
      a non-Ig macromolecule (PSA) was higher for IVP than AI calves. This might
      indicate a more selective absorption in AI calves in favor of IgG. Acidosis
      around birth affected immunoglobulin absorption negatively. IVP-defined calves
      had significantly lower cortisol levels the first 3h after birth and during an
      ACTH-challenge and a lower IgG absorption efficiency, which might indicate a mild
      degree of organ dysmaturity in these calves.

PMID- 11841903
TI  - Insulin-like growth factor I enhances gonadotropin-releasing hormone-stimulated
      luteinizing hormone release from bovine anterior pituitary cells.
AB  - The role of insulin-like growth factor I (IGF-I) in the release of luteinizing
      hormone (LH) is unclear in ruminants. In the present study, the effects of IGF-I
      on the release of LH stimulated by gonadotropin-releasing hormone (GnRH) were
      examined in primary cultures of bovine anterior pituitary (AP) cells, and the
      interaction between estradiol-17beta (E(2)) and IGF-I was characterized.
      GnRH(100nM)-stimulated LH release from the cultured cells was increased (P<0.05)
      12, 24 and 36h after addition of IGF-I (250ng/ml), with a maximum at 12h
      (48.4ng/ml media versus 35.4ng/ml media in controls). IGF-I at concentrations of
      25, 250 and 500ng/ml increased the release by 18.7, 24.2 and 28.9%, respectively
      (P<0.05), when compared with controls (37.2ng/ml media). E(2) (10nM), IGF-I
      (250ng/ml) and combined treatment of E(2) plus IGF-I also induced significant
      increases in LH release (P<0.05). The amounts of LH release after treatment with
      E(2) alone was 37.3% greater than with IGF-I alone (39.0ng/ml media versus
      28.4ng/ml media) (P<0.05). When E(2) and IGF-I were added together (45.6ng/ml
      media), the release of LH was significantly greater than with either E(2) alone
      or IGF-I alone (P<0.05). E(2) (10nM) significantly (P<0.05) increased the amount
      of GnRH bound to the cells by 51.6% when compared with controls, however, IGF-I
      (250ng/ml) failed to increase GnRH binding. These results show that IGF-I
      enhances GnRH-stimulated LH release without changing the number of GnRH receptors
      in cattle, and IGF-I interacts with E(2) to increase the response to GnRH.

PMID- 11841904
TI  - Reproductive responses of early postpartum dairy cattle to continuous treatment
      with a GnRH agonist (deslorelin) for 28 days to delay the resumption of
      ovulation.
AB  - An experiment was conducted to investigate the potential of chronic delivery of a
      potent GnRH agonist (deslorelin) via subcutaneous implants to delay the
      resumption of ovulatory cycles in postpartum dairy cattle. Cows received either a
      single deslorelin implant (n=40; DES) within 7 days of calving or were untreated
      (n=24; CON). Blood samples were collected thrice weekly during the period the
      implants were in place. Plasma concentrations of progesterone (P4) and 17beta
      oestradiol (E2) were measured along with selected serum metabolites. Implants
      were removed after 28 days and cattle monitored daily for behavioral oestrus.
      Serial weekly blood samples were collected to detect the occurrence of ovulation.
      Cows were artificially inseminated as they were detected in oestrus from 30 days
      after implant removal. Pregnancy status was subsequently determined by manual
      palpation of uterine contents at strategic intervals. Insertion of implants
      induced ovulation in 3/40 cows as determined by a rise in progesterone 7 days
      later. Deslorelin implants delayed the onset of ovulatory cycles compared with
      untreated herdmates (mean 43.4+/-4.2 versus 57.3+/-1.6 days postpartum; P<0.001).
      A noticeable delay of at least 12 days was observed between implant removal and
      the first animals ovulating. Mean plasma E2 concentrations during the period the
      implants were in place were similar for DES and CON cows that experienced a
      prolonged spontaneous postpartum anoestrus (low P4 >60 days), although both
      groups had concentrations only 20% of CON cows that had ovulated prior to 30 days
      postpartum. The patterns of recovery following implant removal were highly
      variable. A number of DES cows showed a low and transient rise in plasma
      progesterone around 21 days after implant removal. Some cows displayed oestrus
      but did not appear to form a fully functional corpus luteum with this phenomenon
      being more prevalent among DES cows (7 of 37 versus 1 of 21; P<0.05). Overall,
      significantly more DES cows were detected in oestrus without ovulating compared
      to CON cows. Final pregnancy rates did not differ between DES and CON groups. The
      mean time to conception for DES cows was longer (21.2+/-5.6 versus 41.1+/-7.4
      days, CON versus DES; P<0.01). This difference was not present if the time from
      first ovulation to conception was compared (50.5+/-5.3 versus 43.5+/-9.3 days,
      CON versus DES; P>0.05). Deslorelin implants provided a reliable method of
      inducing anoestrus when treatment was initiated prior to 3 days postpartum. A
      variable pattern of recovery was observed which delayed conception but did not
      ultimately reduce the final proportion pregnant at the completion of mating. The
      study demonstrates the potential of GnRH agonists to control postpartum
      reproductive function to manipulate the fertility of dairy cows.

PMID- 11841905
TI  - Temporary suppression of pulsatile LH release following a single injection of a
      GnRH agonist (deslorelin) in ovariectomised Holstein dairy cows.
AB  - The objective of the experiment was to investigate the potential for using a
      single injection of the GnRH agonist [D-Trp(6), Pro(9)-des-Gly(10)-NH(2)] GnRH
      ethylamide (deslorelin) to suppress LH secretion in ovariectomised Holstein cows.
      Each dose of 10, 100 and 1000 microg deslorelin was injected intravenously into
      each of four ovariectomised cows on day 0. Blood samples were collected hourly on
      day 0 to profile the induced LH release. Frequent serial blood samples were
      collected at 10min intervals over 4h on days -3, -1, +2, +4 and +6. The injection
      of deslorelin induced a surge-like release of LH that begun within 1h in all
      cows. There was no difference between deslorelin doses in terms of maximum LH
      concentration, area under the LH curve (AUC) or log(10)(AUC). The average
      interval from injection to maximum LH concentration was longer for cows receiving
      1000 microg than in those receiving 10 microg (3.5 versus 1.5h; P<0.01), though
      no different to 100 microg (2.8h; P>0.1). This relationship was described by a
      logarithmic function of deslorelin dose in micrograms (R(2)=73.3%, P<0.01). Pre
      treatment smoothed mean LH concentration was significantly correlated with peak
      LH concentration of the induced surge: max_LH=5.37+9.57 x pre-amplitude
      (R(2)=33.2%, P=0.05). Similarly, LH pulse amplitude pre-deslorelin was also
      correlated with peak LH of the induced surge max_LH=0.07+12.9 x pre-amplitude
      (R(2)=53.7%, P=0.07). Pulsatile release of LH was suppressed only with the 1000
      microg dose on day +2. Suppression was characterised by a reduction in mean LH,
      smoothed mean LH and LH pulse amplitude. By day +4, LH parameters were no
      different to pre-treatment ones. Pulse frequency was not affected by the
      treatment, although a small non-significant reduction at day +2 for 1000 microg
      dose was observed (3.9 versus 2.8, P=0.14). In conclusion, temporary suppression
      of LH output for at least 48h occurred following a single intravenous injection
      of 1000 microg of deslorelin, even though there were similar peak LH
      concentrations were for the three doses.

PMID- 11841906
TI  - Restoration of LH output and 17beta-oestradiol responsiveness in acutely
      ovariectomised holstein dairy cows pre-treated with a GnRH agonist (deslorelin)
      for 10 days.
AB  - The objectives of the study were firstly to identify the role of the ovary in
      maintaining plasma luteinising hormone (LH) concentrations in cows treated with
      an implant of a potent GnRH agonist (deslorelin), and secondly to characterise
      the changes in LH following ovariectomy (OVX) in the same animals. Oestrus was
      synchronised in mature Holstein dairy cows and deslorelin implants were inserted
      17 days later into two-third of the cows. A further 10 days later (day 0) all
      cows had bilateral OVX performed. A control group (CON; n=4) received no
      treatment and had blood samples collected at 15-min intervals for 8h on the day
      prior to OVX (day -1) and similarly on days 4 and 10. One group (DES_IN; n=4) had
      implants in place for the duration of the study while another group had implants
      removed (DES_OUT; n=4) at the time of OVX. DES_IN cows were sampled hourly at
      each sampling session (days -1, +4 and +10), whereas DES_OUT cows were sampled
      similarly to CON except on day -1 when hourly samples were collected. Predictable
      post-operative increases in mean LH (0.61 ng/ml versus 1.79 ng/ml; P<0.01) and LH
      pulse amplitude (0.66 ng/ml versus 1.56 ng/ml; day -1 versus day +10; P<0.01)
      occurred after CON cows were ovariectomised. Smoothed LH means showed a delayed
      effect of time compared to arithmetic means. Pulse frequency was unchanged
      following OVX in CON cows. A comparison of all cows that had been treated with
      deslorelin from day -1 showed a significant elevation of smoothed mean LH
      compared to untreated cows (0.80 ng/ml versus 0.34 ng/ml; DES_IN and DES_OUT
      versus CON; P<0.05). DES_IN cows had a 54% reduction in mean LH from day -1 to +4
      following OVX (1.05 ng/ml versus 0.48 ng/ml; P<0.01) indicating the probable
      involvement of the ovary in the maintenance of elevated basal LH. No further
      reduction was detected by day +10. The LH response to an intramuscular (IM)
      injection of 500 microg 17beta-oestradiol (E2) on day +11 varied significantly
      between treatment groups (P<0.01). CON cows showed a typical LH surge, reaching
      maximum concentrations (10.3 ng/ml) at 17.3h post-injection. Even though low
      amplitude LH pulsatility had been restored in DES_OUT cows by day +4, there was
      an inconsistent response to E2 on day +12; one cow had an apparently normal surge
      yet, others showed only attenuated responses. Pulse amplitude in DES_OUT cows was
      lower at days +4 and +10 compared to CON (P<0.05). DES_IN cows did not produce
      any surge after E2. Mean LH prior to OVX (day -1) remained unchanged following
      the 500 microg oestradiol injection (0.38 ng/ml versus 0.45 ng/ml pre-E2 versus
      post-E2 compared to 1.05 ng/ml pre-OVX). The results of this experiment
      implicated ovarian involvement in maintaining elevated basal LH output in cows
      that were chronically treated with a GnRH agonist. Individual cows varied in
      their LH surge response to exogenous E2 given 12 days after implant removal, even
      though LH pulse amplitude and frequency had been restored.

PMID- 11841907
TI  - Development of in vitro embryo production systems for red deer (Cervus elaphus).
      Part 1. Effect of epithelial oviductal monolayers and heparin on in vitro sperm
      motility and penetration of in vitro matured oocytes.
AB  - In vitro fertilisation (IVF) protocols for red deer have yielded low
      fertilisation rates, with no embryo development beyond the eight-cell stage when
      heparin was used as the in vitro capacitation agent. As this low fertilisation
      rate may result from reduced motility, the present study investigated the use of
      red deer oviduct epithelial cell monolayers (COEM) and conditioned medium (Cm)
      from the monolayers to maintain red deer sperm motility in vitro. A second
      experiment compared the fertilisability of red deer sperm pre-incubated for 4-12h
      on COEM or for 4h in TALP medium supplemented with 20 microg of heparin.COEM was
      superior in maintaining red deer sperm motility compared with either Sp-TALP
      alone or Cm (P<0.05). COEM sustained sperm motility at levels comparable to the
      initial motility over the 24h period. The motility of sperm incubated in Sp-TALP
      and Cm was similar and had declined to less than 10% by 4h and no motile sperm
      were observed by 8h. Overall, the penetration rates of in vitro red deer oocytes
      were low (5-28%) regardless of sperm treatment. Sperm pre-incubated on COEM
      penetrated more oocytes than sperm incubated with heparin (P<0.001). Penetration
      rates were similar for 4-12h pre-incubation of sperm on COEM (P>0.50).
      Penetration rates were greater across all treatments when both sperm and oocytes
      were co-incubated for 24h compared to 12h (P<0.001). There were no differences in
      penetration rates among the four donor stags used in the study. It was concluded
      that COEM sustains red deer sperm motility in vitro during the 24h observation
      period. Pre-incubating sperm on COEM does increase sperm penetration rates
      compared with heparin alone, but at a rate too low and variable to be used on a
      routine basis. Overall, the penetration rates were comparable to those previously
      reported for red deer even though differences in heparin concentration,
      fertilisation systems and stags were used.

PMID- 11841908
TI  - Development of in vitro embryo production systems for red deer (Cervus elaphus).
      Part 2. The timing of in vitro nuclear oocyte maturation.
AB  - The time course of in vitro red deer nuclear oocyte maturation was determined.
      Ovaries were obtained at slaughter and oocytes were aspirated from follicles
      greater than 2mm in diameter. Oocytes with compact cumulus cells were matured in
      50 microl microdrops (10 per drop) under mineral oil containing TCM 199
      supplemented with 0.33 mM pyruvate, 10 microg LH and FSH, 1 microg oestradiol and
      10% foetal bovine serum. Oocytes were matured at 39 degrees C and 5% CO(2) in
      air. At 3h intervals (0-27 h) oocytes were removed from incubation, cumulus
      expansion scored and removed, and fixed oocytes in ethanol:acetic acid (3:1) for
      48 h. Oocytes were stained with lacmoid (1%) and nuclear maturation assessed.
      Oocytes were arrested in the germinal vesicle (GV) stage at aspiration and up to
      6h of incubation. The nuclear membrane began to disperse after 6h and by 10.6+/
      0.6h of incubation 75% of the oocytes exhibited germinal vesicle breakdown
      (GVBD). The mean time for 50% of the oocytes to reach metaphase one (MI) and
      metaphase two (MII) was 11.7+/-0.4 and 24.8+/-0.9h, respectively. Cumulus
      oophorus were tightly compacted at aspiration and did not begin expansion until
      12h of culture. Full expansion was complete by 18 h of culture. Corona radiata
      cells did not begin expansion until 15 h and were fully expanded by 24h. Results
      indicate that in vitro red deer oocyte maturation follows a similar time course
      of nuclear maturation as reported for bovine and ovine oocytes.

PMID- 11841909
TI  - Development of in vitro embryo production systems for red deer (Cervus elaphus).
      Part 3. In vitro fertilisation using sheep serum as a capacitating agent and the
      subsequent birth of calves.
AB  - The following experiments investigated the use of sheep serum (SS) as a
      capacitating agent for red deer (Cervus elaphus) sperm during in vitro
      fertilisation. Red deer oocytes were collected at slaughter and matured in vitro
      for 24h in TCM-199 supplemented with 10% foetal calf serum, 10 microg ml(-1) FSH
      and LH, and 1microg ml(-1) of oestradiol. Fertilisation medium was IVF-SOF
      modified to contain 5mM Ca(2+) and no glucose. Experiment 1 investigated the
      addition of heparin, BSA (8 mg ml(-1)) or 20% SS. All oocytes were penetrated
      when IVF-SOF was supplemented with SS compared to 10 and 0% penetration when
      either heparin or BSA was present (P<0.01). However, 43.8% of these oocytes were
      polyspermic when the medium contained SS. In Experiment 2, the effect of sperm
      concentration on penetration rates during in vitro fertilisation was
      investigated. Total sperm penetration and monospermic penetration rates increased
      with increased sperm concentrations in a log linear manner (P<0.001) and both
      approached an asymptote at 0.4 x 10(6) sperm ml(-1) with 93.6 and 77% for total
      and monospermic penetration, respectively. Polyspermic fertilisation also
      increased with increasing sperm concentrations (P<0.05) but was variable (range
      3.5+/-4.2 to 42.3+/-10.6%), especially at the lower sperm concentrations.
      Experiment 3 investigated the viability of these oocytes after transfer into red
      deer recipients. Fifteen 2- and 4-cell embryos were transferred into the oviducts
      of synchronized recipients 28 h post in vitro insemination. An additional
      fourteen embryos (8-10 cell) were transferred into synchronised recipients after
      48 h of in vitro culture in either SOFaaBSA (n=10) or on red deer epithelial
      oviduct monolayers (n=4). Five (33% 5/15) of the recipients that received 2- and
      4-cell embryos were pregnant at Day 45 (verified by ultrasonography) and four
      recipients subsequently calved. One recipient receiving an embryo cultured in
      SOFaaBSA was pregnant at Day 45 and subsequently calved. The birth of five normal
      calves indicate that full developmental competence of red deer oocytes matured
      and fertilised in vitro can be achieved by the techniques described.

PMID- 11841910
TI  - Effects of single nucleotide polymorphisms in the 5'-flanking region of heat
      shock protein 70.2 gene on semen quality in boars.
AB  - This study aims to elucidate the effects of single nucleotide polymorphisms
      (SNPs) in the 5'-flanking region of porcine heat shock protein 70.2 gene
      (HSP70.2) on semen quality in boars. Genomic DNA isolated from 55 boars (41
      Duroc, nine Landrace, and five Yorkshire) was subjected to PCR amplification of
      the 5'-flanking region of HSP70.2. The nucleotide sequences were determined by
      automated sequencing. Five SNPs (sites 44, 232, 250, 345, and 393) were detected
      in this region. Semen quality was evaluated in terms of sperm motility,
      percentage of normal sperm, percentage of sperm with proximal plasma droplet,
      percentage of abnormal sperm, sperm concentration, semen volume per ejaculate and
      total sperm number per ejaculate. The effect of the SNPs on semen quality was
      evaluated based on breed-corrected data within a season. During the cool season,
      the sperm motility of boars with AA genotype at the 232 site was significantly
      higher than that of boars with CC genotype (P<0.05). Meanwhile, boars with AC
      genotype at the 232 site had higher total sperm number per ejaculate than did
      those with CC genotype. In the hot season, heterozygotes at both the 232 and 250
      sites had significantly higher total sperm number of per ejaculate than AA
      homozygotes (P<0.05). Semen volume of boars with TT and TC genotypes at the 345
      site was significantly larger than that of those with CC genotype (P<0.05).
      Meanwhile, semen quality for boars with TT genotype at the 345 site was
      significantly higher than that of boars with TC or CC genotype (P<0.05), that is
      the semen contained higher percentages of normal sperm and lower percentages of
      abnormal sperm or sperm with proximal plasma droplets. Results herein suggest
      that the SNPs in the 5'-flanking region of porcine HSP70.2 are associated with
      semen quality traits in the hot season.

PMID- 11841911
TI  - Growth hormone can regulate functions of porcine ovarian granulosa cells through
      the cAMP/protein kinase A system.
AB  - The action of growth hormone (GH) on the production of hormones, growth factors,
      growth factor binding protein and the occurrence of apoptosis in porcine ovarian
      granulosa cells, as well as the role of cAMP-stimulated protein kinase A (PKA) in
      the mediation of these effects, were studied. For this purpose, the effects of
      exogenous pGH (1-10,000 ng/ml), PKA blockers KT5720 (100 ng/ml) and Rp-cAMPS
      (1micromol), alone and in combination, on insulin-like growth factor type I (IGF
      I), insulin-like binding protein 3 (IGFBP-3), oxytocin (OT) and prostaglandin F
      alpha (PGF) secretion, PKA and cAMP response element binding transcription factor
      (CREB) content and the occurrence of apoptosis were investigated. It was found
      (using RIA/IRMA) that GH addition to culture medium significantly stimulated IGF
      I and PGF release and inhibited IGFBP-3 and OT secretion. GH significantly
      decreased the incidence of apoptosis (TUNEL method) in cultured cells.
      Immunocytochemical study and Western immunoblotting showed, that addition of GH
      caused a dramatic increase in the accumulation of immunoreactive PKA within the
      cells, whilst Western blotting did not reveal marked influence of GH on content
      of CREB in cell lysates. PKA blockers, given alone, were able to decrease IGFBP-3
      output (Rp-cAMPS, but not KT5720), reduce basal OT release (either Rp-cAMPS and
      KT5720) and increase PGF accumulation (KT5720, but not Rp-cAMPS). Furthermore,
      PKA blockers were able to prevent stimulatory effects of GH on IGF-I and PGF
      release, and inhibitory effect of GH on IGFBP-3, OT output and on apoptosis.
      These observations suggest the involvement of GH and a PKA-dependent
      intracellular mechanism in the control of IGF-I, IGFBP-3, OT, PGF, cAMP and
      apoptosis in porcine ovarian granulosa cells. Stimulation of PKA by GH and the
      prevention of GH-induced effects by PKA blockers suggest that both stimulatory
      and inhibitory effects of GH on porcine ovarian cells are probably mediated by
      the cAMP/PKA system.

PMID- 11841912
TI  - Effect of repeated ACTH-stimulation on early embryonic development and hormonal
      profiles in sows.
AB  - This study was conducted to evaluate the effect of adrenal stimulation by
      synthetic adrenocorticotrophic hormone (ACTH) on the first 2 days of pregnancy in
      22 multiparous sows. The experiment was performed during the second oestrus after
      weaning and the sows were divided into one control (C-group) and one experiment
      group (E-group). To determine the time of ovulation, transrectal ultrasonographic
      examination was performed. E-group sows were treated repeatedly with 0.1 mg/kg
      bodyweight of synthetic ACTH (tetracosactide) i.v. 4-8h after ovulation and
      continuing every 6h, until slaughter. Blood samples were collected every second
      hour from about 12h before expected ovulation until slaughter and were analyzed
      for cortisol, prostaglandin F(2 alpha) -metabolite, and progesterone (P(4)). All
      sows were slaughtered approximately 48 h after ovulation and the isthmic part of
      the oviduct was divided into three equally long segments and flushed separately
      with phosphate buffered saline (PBS). The uterine horns were also flushed with
      PBS. The embryos of the E-group sows tended (P=0.056) to have a lower cleavage
      rate than the embryos of the C-group sows but there was no difference between
      groups in oviductal transport rate of the embryos. In the E-group, significantly
      (P<0.05) more sows had only embryos with <20 spermatozoa attached to the ZP
      compared with the C-group. The plasma concentration of cortisol was significantly
      higher (P<0.0001) in the E-group sows during the time of treatment while the
      baseline level of prostaglandin F(2 alpha) -metabolite was significantly lower.
      The baseline level of progesterone increased in both groups after ovulation but
      there was no significant difference between the groups. Repeated ACTH-stimulation
      (1) had no effect on the oviductal transport rate of the embryos, (2) had a
      negative effect on the embryo development, (3) and caused a changed endocrine
      profile that might have changed oviductal milieu affecting embryo development.

PMID- 11841913
TI  - The relationship between rabbit semen characteristics and reproductive
      performance after artificial insemination.
AB  - The relationships between several rabbit buck semen traits, concerning either the
      ejaculate or the dose inseminated (volume, mass motility, pH, percentage of
      motile sperm (PMS), concentration, number of total and motile sperm per ejaculate
      and per insemination dose) and the reproductive performance of does was
      investigated in 839 inseminations involving 54 bucks and 111 does. Four genetic
      types were involved: INRA1601 strain (A), INRA2066 strain (B) and the two
      reciprocal crossbreds (AB and BA). The mating design was A x A, B x B, (AB or BA)
      x (AB or BA). Semen was diluted (1:9) and a constant volume of 0.5 ml was
      inseminated 2-4h after collection. Therefore, the total number of spermatozoa per
      dose was variable and proportional to the initial concentration. Mass motility
      significantly influenced the kindling rate. Taken separately, volume, PMS and
      concentration did not influence the kindling rate but their product, the number
      of motile sperm per ejaculate, did. Litter size (total born) was significantly
      influenced by concentration and all variables depending on it, particularly the
      number of total and motile sperm per dose. However, reproductive performances
      were predominantly influenced by the physiological status of the does at
      insemination (lactation stage and receptivity).

PMID- 11841915
TI  - Development of NADPH-diaphorase/nitric oxide synthase in the brain of the urodele
      amphibian Pleurodeles waltl.
AB  - In the present study, the ontogenesis of nitrergic neurons has been studied in
      the urodele amphibian Pleurodeles waltl by means of NADPH-diaphorase (NADPHd)
      histochemistry and neuronal nitric oxide synthase (NOS) immunohistochemistry.
      Embryonic and larval stages were studied. Except for the olfactory fibers and
      glomeruli, both methods were equally suitable to reveal nitrergic structures in
      the brain. The earliest positive neurons were observed in the inferior reticular
      nucleus (Ri) in the caudal rhombencephalon at embryonic stage 30. At stage 33b,
      weakly reactive cells appeared in the tegmentum of the mesencephalon and isthmus,
      in the ventral hypothalamus (VH), and in the proximity of the solitary tract
      (sol). At initial larval stages (stages 34-38), two new groups appeared in the
      caudal telencephalon (future amygdaloid complex (Am)) and in the middle reticular
      nucleus (Rm) of the rhombencephalon. During the active larval life (stages 39
      55c) the nitrergic system developed progressively both in number of cells and
      fiber tracts. At stages 39-42 reactive cells were found in the inner granular
      layer (igl) of the olfactory bulb, the telencephalic pallium, the pretectal
      region, the optic tectum (OT) and retina. New populations of nitrergic cells
      appear during the second half of the larval period (stages 52-55). Rostrally,
      reactive cells were found in the telencephalic diagonal band (DB) nucleus, medial
      septum and in the thalamic eminence (TE), whereas caudally cells appeared in the
      raphe (Ra) and the descending trigeminal nucleus (Vd). The last changes occurred
      during the juvenile period (metamorphic climax), when cells of the spinal cord
      (sc) and the preoptic area became positive. The sequence of appearance of
      nitrergic cells revealed a first involvement of this system in reticulospinal
      control, likely influencing locomotor behavior. As development proceeds, cells in
      different sensory systems expressed progressively nitric oxide synthase in a
      pattern that shows many similarities with amniotes.

PMID- 11841914
TI  - Principles of rat subcortical forebrain organization: a study using histological
      techniques and multiple fluorescence labeling.
AB  - In the present study, we introduce new views on neuro- and chemoarchitectonics of
      the rat forebrain subcortex deduced from traditional and current concepts of
      anatomical organization and from our own results. It is based on double and
      triple immunofluorescence of markers for transmitter-related enzymes, calcium
      binding proteins, receptor proteins, myelin basic protein (MBP) and
      neuropeptides, and on histological cell/myelin stains. The main findings can be
      summarized as follows: (i) the dorsal striatum of rat and other myomorph rodents
      reveals a small caudate equivalent homotopic to the caudate nucleus (C) of other
      mammals, and a large putamen (Pu). (ii) Shell and core can be distinguished also
      in the 'rostral pole' of nucleus accumbens (ACC) with the calretinin/calbindin
      and neuropeptide Y (NPY) immunostaining. The shell reveals characteristics of a
      genuine striatal but not of an extended amygdala (EA) subunit. (iii) EA and
      lateral septum show striking similarities in structure and fiber connections and
      may therefore represent a separate parastriatal complex. (iv) The meandering
      dense layer (DL) of olfactory tubercle (OT) forms longitudinal gyrus- and sulcus
      like structures converging in its rostral pole. (v) The core regions of the
      islands of Calleja that border the ventral pallidum (VP) sharing some of its
      features are invaded by myelinated fibers of the medial forebrain bundle (MFB).
      The island of Calleja magna is also apposed to an inconspicuous, slender dorsal
      appendage of VP. (vi) The VP is composed of a large dorsal reticulated part
      traversed by the myelinated GABAergic parvalbumin-immunoreactive axons of the MFB
      and a slender ventral non-reticulate part close to the islands of Calleja. (vii)
      Considering their close association to the limbic system, ventral striatum (VS)
      and VP may represent the oldest part of basal ganglia, whereas dorsal
      striatopallidal subunits were progressively developed in parallel to the growing
      neocortical influence on motor behavior.

PMID- 11841917
TI  - Intracerebroventricular infusion of neuropeptide Y up-regulates synthesis and
      accumulation of luteinizing hormone but not follicle stimulating hormone in the
      pituitary cells of prepubertal female lambs.
AB  - Neuropeptide Y (NPY) is a putative neuroregulator of the reproductive axis in the
      central nervous system. In this study we evaluated the effects of central
      infusion of exogenous NPY on the secretory activity of pituitary gonadotrophic
      cells in prepubertal lambs. Immature female Merino sheep (n=12) were infused of
      Ringer solution (control) or 50 microg of NPY to the third ventricle for 5 min
      and then slaughtered 3 h later. Immunoreactive luteinizing hormone (LH) and
      follicle stimulating hormone (FSH) cells were localised by immunohistochemistry
      using antibody raised against LHbeta and FSHbeta. Messenger RNA analyses were
      performed by in situ hybridisation using sense and antisense riboprobes produced
      from beta subunits of LH and FSH cDNA clones. The results were generated by
      computer image analysis to determine the area fraction occupied by immunoreactive
      and/or hybridising cells and optical density for immunostaining and hybridisation
      signal. LH in the blood plasma was determined by radioimmunoassay. It was found,
      that in the lambs infused with NPY the area fraction and optical density for
      immunoreactive LH cells and mRNA LHbeta-expressing cells increased significantly
      (P<0.001), compared to the vehicle-infused animals. The concentration of LH in
      the blood plasma did not differ between control and treated groups. The NPY
      infusions had no effect on the immunoreactivity of FSH cells or on expression of
      mRNA for FSHbeta. In conclusion we suggest that NPY may be an important component
      of mechanisms stimulating the synthesis and storage but not the release of LH in
      the pituitary gonadotrophs from prepubertal female sheep. In addition, this
      effect is specific for LH, no such effect was apparent on FSH.

PMID- 11841916
TI  - Cocaine- and amphetamine-regulated transcript peptide-immunoreactivity in
      adrenergic C1 neurons projecting to the intermediolateral cell column of the rat.
AB  - Cocaine- and amphetamine-regulated transcript (CART) peptide-immunoreactivity was
      detected in neurons of the rostral ventrolateral medulla (RVLM), but few in the
      caudal ventrolateral medulla (CVLM). Double-labeling the medullary sections with
      sheep polyclonal phenylethanolamine N-methyltransferase-antiserum (PNMT) or
      monoclonal tyrosine hydroxylase-antibody and rabbit polyclonal CART peptide
      antiserum revealed that nearly all adrenergic cells in the C1 area were CART
      peptide-positive and vice versa; tyrosine hydroxylase-positive cells in the A1
      area were not. In the thoracolumbar spinal cord, neurons in the intermediolateral
      cell column (IML) and other sympathetic autonomic nuclei were CART peptide
      positive; some of these were contacted by immunoreactive fibers arising from the
      lateral funiculus. By immuno-electron microscopy, axon terminals containing
      closely packed agranular CART peptide-immunoreactive vesicles appeared to make
      synaptic contacts with immunoreactive dendrites and soma in the IML, albeit the
      incidence of such contacts was low. Microinjection of the retrograde tracer
      Fluorogold into the lateral horn area of the T1-T3 spinal segments labeled a
      population of neurons in the C1 area, many of which were also CART peptide
      positive. The results indicate that CART peptide-immunoreactivity is expressed in
      C1 adrenergic neurons, some of which project to the thoracolumbar spinal cord.
      The presence of this novel peptide in C1 adrenergic neurons underscores the
      multiplicity of putative transmitters that may be involved in signaling between
      putative cardiovascular neurons in the medulla oblongata and sympathetic
      preganglionic neurons (SPNs) in the spinal cord.

PMID- 11841918
TI  - Biochemical and autoradiographic studies of the central noradrenergic system in
      dystonia musculorum mutant mice.
AB  - The autosomal recessive mutation dystonia musculorum (dt(J)/dt(J)) causes
      degenerative alterations of peripheral and central sensory pathways leading to
      ataxia. To determine the consequences of this pathology on the central
      noradrenergic (NA) system, NA contents were measured by high-performance liquid
      chromatography (HPLC) in 22 brain regions and spinal cord, while NA transporters,
      or uptake sites, were evaluated by quantitative ligand binding autoradiography,
      using [3H]nisoxetine, in wild-type and dt(J)/dt(J) mutant mice. The only
      significant differences in NA contents between the two genotypes were increased
      levels in hypothalamus and mesencephalic dopaminergic regions A9/A10 of
      dt(J)/dt(J) mutants. The dt(J)/dt(J) spinal cord showed a similar result, but its
      NA content remained unchanged when taking into account its reduced volume.
      Binding to NA transporters revealed increased densities in sensory nuclei of
      cranial nerves, granular layer of the cerebellar cortex, as well as in cerebellar
      related and basal ganglia structures, such as the lateral cuneate nucleus,
      pontine nuclei, substantia nigra, pontine reticular formation, median raphe
      nucleus and superior colliculus. Forebrain regions were relatively unaffected in
      the dt(J)/dt(J) mutants, although NA transporter densities were higher in
      piriform cortex, hippocampal subdivisions and ventro-anterior thalamic nucleus.
      In contrast, densities of NA transporters were decreased in hypothalamic
      subregions and in two ventrobasal thalamic nuclei. The results are discussed in
      relation to expression of the dystonin gene in normal brain, cellular defects
      resulting from the loss of gene transcription in the dt(J)/dt(J) mutation,
      functional circuits of the central nervous system and some of the phenotypical
      characteristics of dystonia musculorum mutants.

PMID- 11841919
TI  - Role of malondialdehyde-acetaldehyde adducts in liver injury.
AB  - Malondialdehyde and acetaldehyde react together with proteins in a synergistic
      manner and form hybrid protein adducts, designated as MAA adducts. MAA-protein
      adducts are composed of two major products whose structures and mechanism of
      formation have been elucidated. MAA adduct formation, especially in the liver,
      has been demonstrated in vivo during ethanol consumption. These protein adducts
      are capable of inducing a potent immune response, resulting in the generation of
      antibodies against both MAA epitopes, as well as against epitopes on the carrier
      protein. Chronic ethanol administration to rats results in significant
      circulating antibody titers against MAA-adducted proteins, and high anti-MAA
      titers have been associated with the severity of liver damage in humans with
      alcoholic liver disease. In vitro exposure of liver endothelial or hepatic
      stellate cells to MAA adducts induces a proinflammatory and profibrogenic
      response in these cells. Thus, during excessive ethanol consumption, ethanol
      oxidation and ethanol-induced oxidative stress result in the formation of
      acetaldehyde and malondialdehyde, respectively. These aldehydes can react
      together synergistically with proteins and generate MAA adducts, which are very
      immunogenic and possess proinflammatory and profibrogenic properties. By virtue
      of these potentially toxic effects, MAA adducts may play an important role in the
      pathogenesis of alcoholic liver injury.

PMID- 11841920
TI  - Iron regulation of hepatic macrophage TNFalpha expression.
AB  - Sustained TNFalpha induction is central to the pathogenesis of chronic liver
      disease including alcoholic liver disease (ALD). However, molecular understanding
      of this abnormality at the cellular level remains elusive. Redox regulation of NF
      kappaB is critical in the transcriptional control of TNFalpha expression.
      Evidence supports that increased iron storage in hepatic macrophages (HM) is
      causally associated with accentuated and sustained NF-kappaB activation in these
      cells in ALD. Treatment of cultured HM with a lipophilic iron chelator
      (deferiprone) abrogates LPS-induced NF-kappaB activation. HM from an animal model
      of ALD have increased nonheme iron content accompanied by increased generation of
      EPR-detected radicals, NF-kappaB activation, and TNFalpha induction, all of which
      are normalized by ex vivo treatment of the cells with deferiprone. A moderate
      increase in the nonheme iron content in HM by erythrophagocytosis, promotes
      subsequent LPS-stimulated NF-kappaB activation in a hemeoxygenase-dependent
      manner. Recent evidence also suggests a role of intracellular low molecular
      weight iron in the early signal transduction for LPS-mediated NF-kappaB
      activation.

PMID- 11841921
TI  - The "French Paradox" and beyond: neuroprotective effects of polyphenols.
AB  - Chronic ethanol ingestion is known to cause oxidative damage to a number of
      organs including the brain. This is partly due to the ability of ethanol to
      enhance oxygen free radical production and lipid peroxidation. Increase in
      oxidative stress has been regarded as an important underlying factor for a number
      of human health problems including cardiovascular diseases, aging, as well as
      many age-related neurodegenerative diseases. The strikingly low incidences of
      coronary heart diseases (CHD) in France, despite intake of a high-fat diet, have
      been attributed to the consumption of red wine containing high levels of
      polyphenolic compounds. In recent years, understanding the "French Paradox" has
      stimulated new research interest to investigate whether polyphenolic antioxidants
      may offer protective effects beyond the cardiovascular system, and whether
      polyphenols from other botanical sources may similarly offer beneficial effects
      to human health. Our studies with animal models have provided information clearly
      indicating the ability of grape polyphenols to ameliorate neuronal damages due to
      chronic ethanol consumption. Studies with resveratrol, an important component of
      grape polyphenols, also show protective effects on neuron cell death induced by
      ethanol and other oxidative agents. These studies demonstrate an urgent need to
      extend research beyond the "French Paradox" towards better understanding
      molecular mechanisms of action of polyphenolic compounds and their application to
      human health.

PMID- 11841923
TI  - Gas chromatography mass spectrometry analysis of carboxyethyl-hydroxychroman
      metabolites of alpha- and gamma-tocopherol in human plasma.
AB  - Alpha- and gamma-tocopherol (alpha- and gamma-T, respectively) metabolite
      analysis is of key relevance in the study of vitamin E metabolism. Whilst there
      is information on urinary excretion of the two major metabolites of these vitamin
      E homologues, namely the 2,5,7,8-tetramethyl-2-(beta-carboxyethyl)-6
      hydroxychroman (alpha-CEHC) and 2,7,8-trimethyl-2-(beta-carboxyethyl)-6
      hydroxychroman (gamma-CEHC), their concentration and response to supplements in
      plasma remains poorly investigated. In this study we describe a gas
      chromatography-mass spectrometry (GC/MS)-based assay to measure both alpha- and
      gamma-T and their corresponding CEHC metabolites in human plasma. As an example
      of the application of this method we report data obtained following the
      supplemention of two healthy volunteers with 100 mg of deuterium-labeled gamma-T
      acetate (d(2)-gamma-TAC). Under routine analytical conditions a good linearity in
      the range 0.0025--1 microM was observed for both the alpha- and gamma-CEHC
      deuterated standards. In plasma samples, the detection limit for alpha- and gamma
      CEHC was 2.5 and 5 nmol/l, respectively. The minimum amount of plasma required
      for the assay was 500 microl. The plasma concentrations of alpha-CEHC and gamma
      CEHC in unsupplemented healthy subjects were 12.6 +/-7.5 and 160.7 +/- 44.9
      nmol/l, respectively. In the two volunteers supplemented with 100 mg of d(2)
      gamma-TAC, plasma d(2)-gamma-T concentrations increased 250 to 450-fold 6 h
      postsupplementation. Plasma and urinary d(2)-gamma-CEHC concentrations increased
      20 to 40-fold 9--12 h postsupplementation. Interestingly, the acute increase in
      d(2) gamma-T did not significantly affect the baseline plasma concentrations of
      d(0)-gamma-T and only slight lowered alpha-T concentrations. Likewise, plasma
      alpha-CEHC levels were not influenced and urinary excretion of alpha-CEHC were
      unaltered. This GC/MS method provides a versatile and accurate mean for assessing
      carboxyethyl-hydroxychroman metabolites of vitamin E in plasma.

PMID- 11841922
TI  - Melatonin reduces oxidative damage and increases survival of mice infected with
      Schistosoma mansoni.
AB  - The tropical parasite Schistosoma mansoni causes granulomatous inflammation after
      its eggs lodge in hepatic portal capillaries. In vitro studies indicate that the
      host's response involves the production of reactive oxygen species, although
      whether this occurs in vivo at the site of the infection is unknown. The role of
      oxidative processes in mice infected with S. mansoni was investigated in the
      current study using the antioxidant melatonin. In Experiment 1, the survival rate
      of infected mice with and without daily melatonin (10 mg/kg) administration was
      determined. After 56 d, 25 of 25 infected mice that were diluent treated had
      died. In contrast, 22 or 25 infected mice (88%) given melatonin were still alive
      at 56 d. Of these 22 surviving mice, melatonin injections were continued in 11
      while the 11 others were switched to diluent. Within 10 d, 11 of 11 diluent
      injected mice that were infected with S. mansoni were dead while 6 of 11
      melatonin-treated mice survived. In Experiment 2, S. mansoni-infected mice were
      treated for 30 d with either melatonin or diluent. Uninfected, untreated mice
      served as controls. In these mice, the levels of lipid peroxidation (LPO)
      products, vitamin E, nitric oxide (NO), glutathione (GSH), and superoxide
      dismutase (SOD) activity in the liver, kidney, and spleen were measured. In the
      serum, cholesterol levels and liver damage (alkaline phosphatase (ALP), aspartate
      transaminases (AST), total protein, and albumin) were monitored. In addition,
      peroxynitrite anion (ONOO(-)) in the liver and kidney and inducible nitric oxide
      synthase (iNOS) in the spleen were immunocytochemically localized. Also,
      histopathological changes in the liver, kidney, and spleen were examined. The
      results documented increased LPO and NO levels and decreased vitamin E, GSH, and
      SOD activity in the liver, kidney, and spleen of S. mansoni-infected mice. Also,
      there was an increase in serum cholesterol and evidence of liver damage in the
      infected mice. Immunohistochemical results indicated positive staining of ONOO(-)
      in the liver and kidney and positive iNOS staining in the spleen of S. mansoni
      infected mice. Histopathological observations revealed granuloma formation in the
      liver with eosinophil infiltration, a large number of megakaryocytes in the
      spleen, and degeneration with necrotic cells in some tubules of the kidney cortex
      in the infected mice. Melatonin administration after S. mansoni infection
      prevented most of the previously described changes. These results suggest that
      oxidative processes occur at the site of inflammation and are involved in the
      damaging effects of schistosomiasis and indicate that free radicals may be a
      major component of the disease. Likewise, melatonin, presumably due to its
      antioxidant and free radical scavenging activity, is highly protective against
      the pathological changes associated with schistosomiasis.

PMID- 11841924
TI  - Roles of protein kinase C and alpha-tocopherol in regulation of signal
      transduction for GATA-4 phosphorylation in HL-1 cardiac muscle cells.
AB  - Our previous study demonstrated that endothelin-1 induced a phosphorylation of
      GATA-4 transcription factor, which plays important roles in cardiac hypertrophy
      and failure. The goal of the present study was to determine whether protein
      kinase C (PKC) is involved in the signaling pathway, and, if so, whether alpha
      tocopherol inhibits the GATA-4 phosphorylation. Treatment of HL-1 adult mouse
      cardiac muscle cells with PMA, a known activator of PKC, induced a transient
      phosphorylation of GATA-4. PMA also phosphorylated MEK and ERK, and PMA-induced
      GATA-4 phosphorylation was blocked by an MEK inhibitor, PD98059, suggesting that
      PMA phosphorylates GATA-4 via the MEK-ERK pathway. Treatment of HL-1 cells with 1
      microM PMA for 24 h resulted in a downregulation of PKC. In PKC-downregulated
      cells, PMA- or ET-1-induced GATA-4 phosphorylation was suppressed, suggesting the
      role of PKC in GATA-4 phosphorylation. However, alpha-tocopherol (5--100 microM)
      did not inhibit the phosphorylation of GATA-4 or ERK in HL-1 cells. In contrast,
      alpha-tocopherol potently inhibited the PMA-induced ERK activation in smooth
      muscle cells. Our studies in HL-1 cells showed that PKC inhibitors, such as
      calphostin C and chelerythrin, failed to inhibit the PMA signaling. Furthermore,
      HL-1 cells appear to possess a unique PKC-signaling mechanism as PKC is
      constitutively phosphorylated and PMA did not cause further phosphorylation.
      Thus, in HL-1 cardiac muscle cells, PMA activates the MEK-ERK-GATA-4 pathway,
      apparently via a PKC-independent mechanism.

PMID- 11841925
TI  - Diabetes impairs the enzymatic disposal of 4-hydroxynonenal in rat liver.
AB  - This study assesses whether the HNE accumulation we formerly observed in liver
      microsomes and mitochondria of BB/Wor diabetic rats depends on an increased rate
      of lipoperoxidation or on impairment of enzymatic removal. There are three main
      HNE metabolizing enzymes: glutathione-S-transferase (GST), aldehyde dehydrogenase
      (ALDH), and alcohol dehydrogenase (ADH). In this study we show that GST and ALDH
      activities are reduced in liver microsomes and mitochondria of diabetic rats; in
      contrast, ADH activity remains unchanged. The role of each enzyme in HNE removal
      was evaluated by using enzymatic inhibitors. The roles of both GST and ALDH were
      markedly reduced in diabetic rats, while ADH-mediated consumption was
      significantly increased. However, the higher level of lipohydroperoxides in
      diabetic liver indicated more marked lipoperoxidation. We therefore think that
      HNE accumulation in diabetic liver may depend on both mechanisms: increased
      lipoperoxidation and decreased enzymatic removal. We suggest that glycoxidation
      and/or hyperglycemic pseudohypoxia may be involved in the enzymatic impairment
      observed. Moreover, since HNE exerts toxic effects on enzymes, HNE accumulation,
      deficiency of HNE removal, and production of reactive oxygen species can generate
      vicious circles able to amplify the damage.

PMID- 11841926
TI  - Cellular lipid peroxidation end-products induce apoptosis in human lens
      epithelial cells.
AB  - Hydrogen peroxide (H(2)O(2)), an oxidant present in high concentrations in the
      aqueous humor of the elderly eyes, is known to impart toxicity to the lens--
      apoptosis being one of the toxic events. Since H(2)O(2) causes lipid peroxidation
      leading to the formation of reactive end-products, it is important to investigate
      whether the end-products of lipid peroxidation are involved in the oxidation
      induced apoptosis in the lens. 4-Hydroxynonenal (HNE), a major cytotoxic end
      product of lipid peroxidation, has been shown to mediate oxidative stress-induced
      cell death in many cell types. It has been shown that HNE is cataractogenic in
      micromolar concentrations in vitro, however, the underlying mechanism is not yet
      clearly understood. In the present study we have demonstrated that H(2)O(2) and
      the lipid derived aldehydes, HNE and 4-hydroxyhexenal (HHE), can induce dose- and
      time-dependent loss of cell viability and a simultaneous increase in apoptosis
      involving activation of caspases such as caspase-1, -2, -3, and -8 in the
      cultured human lens epithelial cells. Interestingly, we observed that Z-VAD, a
      broad range inhibitor of caspases, conferred protection against H(2)O(2)- and HNE
      induced apoptosis, suggesting the involvement of caspases in this apoptotic
      system. Using the cationic dye JC-1, early apoptotic changes were assessed
      following 5 h of HNE and H(2)O(2) insult. Though HNE exposure resulted in
      approximately 50% cells to undergo early apoptotic changes, no such changes were
      observed in H(2)O(2) treated cells during this period. Furthermore, apoptosis, as
      determined by quantifying the DNA fragmentation, was apparent at a much earlier
      time period by HNE as opposed to H(2)O(2). Taken together, the results
      demonstrate the apoptotic potential of the lipid peroxidation end-products and
      suggest that H(2)O(2)-induced apoptosis may be mediated by these end-products in
      the lens epithelium.

PMID- 11841928
TI  - New paradigms in the treatment of breast and colorectal cancer--an introduction.

PMID- 11841927
TI  - Hypothesis: the mitochondrial NO(*) signaling pathway, and the transduction of
      nitrosative to oxidative cell signals: an alternative function for cytochrome C
      oxidase.
AB  - Nitric oxide (NO(*)) signaling is diverse, and involves reaction with free
      radicals, metalloproteins, and specific protein amino acid residues. Prominent
      among these interactions are the heme protein soluble guanylate cyclase and
      cysteine residues within several proteins such as caspases, the executors of
      apoptosis. Another well characterized site of NO(*) binding is the terminal
      complex of the mitochondrial respiratory chain, cytochrome c oxidase, although
      the downstream signaling effects of this interaction remain unclear. Recently, it
      has been recognized that the intracellular formation of hydrogen peroxide
      (H(2)O(2)) by controlled mechanisms contributes to what we term "redox tone," and
      so controls the activity and activation thresholds of redox-sensitive signaling
      pathways. In this hypothesis paper, it is proposed that NO(*)-dependent
      modulation of the respiratory chain can control the mitochondrial generation of
      H(2)O(2) for cell signaling purposes without affecting ATP synthesis.

PMID- 11841929
TI  - Rational development of capecitabine.
AB  - Capecitabine is a fluoropyrimidine carbamate that was rationally designed as an
      oral drug capable of mimicking continuous infusion 5-fluorouracil (5-FU) and
      delivering 5-FU preferentially to tumour tissue. Following extensive absorption,
      capecitabine is rapidly converted to 5-FU via a three-step enzymatic pathway. The
      final step depends on thymidine phosphorylase, an enzyme present at higher
      concentrations in malignant compared with normal tissue. This results in the
      delivery of 5-FU preferentially to the tumour site. Capecitabine has demonstrated
      high activity in preclinical xenograft models for a wide range of human solid
      tumours, including those resistant to 5-FU. Phase I studies have determined the
      maximum tolerated dose (MTD) of capecitabine and identified a number of dosage
      regimens, which were subsequently evaluated in a randomised, phase II study as
      first-line treatment for metastatic colorectal cancer. This established an
      intermittent regimen of capecitabine 1250 mg/m2 twice daily for 14 days followed
      by a 7-day rest period as the most appropriate regimen for further clinical
      development.

PMID- 11841930
TI  - Clinical experience of capecitabine in metastatic breast cancer.
AB  - Results from two phase II studies in metastatic breast cancer have shown that the
      novel, tumour-selective fluoropyrimidine capecitabine provides an effective and
      well tolerated therapy in patients with metastatic breast cancer failing or
      resistant to anthracycline and taxane therapy. Response rates of between 20 and
      25% have been observed, with median survival of 12.2-12.6 months. In addition,
      there was an acceptable incidence of adverse events including diarrhoea and hand
      foot syndrome, which can be controlled with a dose reduction. Promising results
      from two further randomised, phase II studies have indicated that capecitabine
      may also play a role in first- and second-line treatment of metastatic breast
      cancer. Capecitabine compared favourably with paclitaxel in anthracycline
      resistant patients and with intravenous (i.v.) CMF
      (cyclophosphamide/methotrexate/5-fluorouracil (5-FU)) in post-menopausal women
      who had received no prior chemotherapy for metastatic disease, with high efficacy
      and good tolerability. The results of these four phase II studies demonstrate
      that capecitabine is active and well tolerated in a range of settings for
      metastatic breast cancer.

PMID- 11841931
TI  - Capecitabine as first-line treatment in colorectal cancer. Pooled data from two
      large, phase III trials.
AB  - The oral, tumour-selective fluoropyrimidine capecitabine represents a major new
      strategy for the treatment of colorectal cancer. Pooled results from two large,
      multicentre, open-label, phase III studies comparing oral capecitabine (1250
      mg/m2 twice daily for 14 days every 3 weeks) with the Mayo Clinic regimen (5
      fluorouracil [5-FU] 425 mg/m2 plus leucovorin 20 mg/m2 days 1-5, every 4 weeks)
      provide information on over 1200 patients receiving first-line chemotherapy for
      metastatic colorectal cancer. Analysis of all randomised patients demonstrated a
      significantly superior overall response rate as assessed by the investigator for
      capecitabine compared with 5-FU/leucovorin (25.7% versus 16.7%, P<0.0002),
      reinforcing the individual trial results. Median time to disease progression,
      overall survival and duration of response were equivalent in the two treatment
      groups. Furthermore, capecitabine showed a superior safety profile compared with
      5-FU/leucovorin, with a significantly lower incidence (P<0.001) of diarrhoea,
      stomatitis, nausea and alopecia, together with a reduced treatment-related
      hospitalisation rate. In addition, the incidence of neutropenic fever/sepsis was
      significantly lower in patients receiving capecitabine.

PMID- 11841932
TI  - Future treatment options with capecitabine in solid tumours.
AB  - The oral fluoropyrimidine, capecitabine is attracting great interest in the
      context of tumour-selective therapy and rationally designed combination regimens.
      Agents such as taxanes upregulate thymidine phosphorylase (TP), and there is
      therefore a clear rationale for their combination with capecitabine. Preclinical
      studies of capecitabine/taxane combination therapy demonstrated synergistic
      antitumour activity and phase I studies showed encouraging efficacy. Therefore, a
      randomised, phase III trial (docetaxel versus docetaxel/capecitabine) has been
      initiated in anthracycline-refractory metastatic breast cancer patients.
      Recruitment is complete. In colorectal cancer, capecitabine/oxaliplatin
      combination therapy is promising and a phase I, dose-finding trial has been
      conducted in patients with refractory metastatic solid tumours. A similar trial
      has evaluated capecitabine/irinotecan combination treatment. Capecitabine is also
      being investigated as adjuvant therapy for colorectal and breast cancers. The
      primary objective of the ongoing X-ACT trial in almost 2000 Dukes' C colon cancer
      patients is to demonstrate at least equivalent disease-free survival between
      capecitabine and the Mayo Clinic regimen. In addition, the CALGB is planning a
      randomised, phase III trial of capecitabine versus doxorubicin/cyclophosphamide
      or cyclophosphamide/methotrexate/5-fluorouracil (CMF) as adjuvant treatment in
      high-risk, node-negative breast cancer patients aged >65 years.

PMID- 11841933
TI  - Diversity-oriented organic synthesis and proteomics. New frontiers for chemistry
      & biology.

PMID- 11841934
TI  - Deacetylase enzymes: biological functions and the use of small-molecule
      inhibitors.

PMID- 11841935
TI  - Engineering selectivity and discrimination into ligand-receptor interfaces.
AB  - The reengineering of protein-ligand (or enzyme-substrate) interfaces using a
      combination of chemical and genetic methods has become an increasingly common
      technique to create new tools to manipulate and study biological systems. Many
      applications of ligand receptor engineering require that the engineered ligand
      and receptor function independently of endogenous ligands and receptors.
      Engineered ligands must selectively interact with modified receptors, and
      modified receptors must effectively discriminate against endogenous ligands. A
      variety of chemical design strategies have been used to reengineer ligand
      receptor interfaces. The advantages and limitations of various strategies, which
      involve the manipulation of hydrophobic, polar, and charged residues, are
      compared. New design strategies and potential applications of ligand-receptor
      engineering are also discussed.

PMID- 11841936
TI  - Mutant tyrosine kinases with unnatural nucleotide specificity retain the
      structure and phospho-acceptor specificity of the wild-type enzyme.
AB  - The direct substrates of one protein kinase in a cell can be identified by
      mutation of the ATP binding pocket to allow an unnatural ATP analog to be
      accepted exclusively by the engineered kinase. Here, we present structural and
      functional assessment of peptide specificity of mutant protein kinases with
      unnatural ATP analogs. The crystal structure (2.8 A resolution) of c-Src (T338G)
      with N(6)-(benzyl) ADP bound shows that the creation of a unique nucleotide
      binding pocket does not alter the phospho-acceptor binding site of the kinase. A
      panel of optimal peptide substrates of defined sequence, as well as a degenerate
      peptide library, was utilized to assess the phospho-acceptor specificity of the
      engineered "traceable" kinases. The specificity profiles for the mutant kinases
      were found to be identical to those of their wild-type counterparts.

PMID- 11841937
TI  - A chemical genetic screen for direct v-Src substrates reveals ordered assembly of
      a retrograde signaling pathway.
AB  - Using an ATP analog that is a specific substrate for an analog-specific allele of
      v-Src, we identified several novel cytoskeletal substrates that control actin
      assembly processes. A screen for less abundant v-Src substrates revealed the
      scaffolding protein Dok-1 as a direct substrate of v-Src. Further studies suggest
      that v-Src phosphorylation sites on Dok-1 are critical for its binding to RasGAP
      and Csk, negative regulators of Src signaling. This results in the downregulation
      of growth-promoting signals of the Src family kinases and the Ras pathway.
      Identification of the direct substrates of v-Src leads to a model for the precise
      order of assembly of a retrograde signaling pathway in v-Src-transformed cells
      and has provided new insight into the balance between those signals that promote
      cell transformation mediated by v-Src catalyzed tyrosine phosphorylation and
      those that inhibit it.

PMID- 11841938
TI  - Synthesis of calcineurin-resistant derivatives of FK506 and selection of
      compensatory receptors.
AB  - We used olefin metathesis to synthesize C40 derivatives of FK506 and measured
      their ability, when complexed to FKBP12, to inhibit calcineurin's phosphatase
      activity. We identified modular dimerization domains (CABs) containing segments
      of the calcineurin A and B polypeptides. These CABs respond to FK506 both when
      overexpressed in mammalian cells and in yeast or mammalian three-hybrid assays.
      Using chemical genetic selection, we identified compensatory mutant CABs that
      respond to a calcineurin-resistant FK506 derivative at concentrations well below
      the response threshold for CABs containing only wild-type calcineurin sequence.
      These reagents provide a small molecule-protein combination orthogonal to
      existing dimerizer systems and may be used with existing systems to increase the
      complexity of induced-proximity experiments. This new use of the "bump-hole"
      strategy protects target cells from complications arising from the inhibition of
      endogenous calcineurin.

PMID- 11841939
TI  - Novel mastoparan analogs induce differential secretion from mast cells.
AB  - Cationic amphiphilic peptides stimulate secretion via a receptor-independent
      action upon G proteins. We have previously utilized chimeric analogs of
      mastoparan (MP), including galparan (galanin(1-13)-MP ), as molecular probes of
      secretion. Here, we further resolve the structure-activity relationship of
      peptidyl secretagogs, including rationally designed chimeric MP analogs. The
      secretory efficacies of 10 MP analogs were significantly higher than 45 unrelated
      basic peptides. Comparative studies identified MP analogs that are differential
      secretagogs for 5-hydroxytryptamine (5-HT) and beta-hexosaminidase. Peptide
      induced activation of phospholipase D (PLD), an enzyme intimately involved in
      regulated exocytosis [5], correlated with the secretion of beta-hexosaminidase
      but not 5-HT. Thus, these data indicate that different mechanisms are responsible
      for the exocytosis of 5-HT and beta-hexosaminidase, respectively. Moreover,
      mastoparan analogs are novel tools for probing the molecular details of
      exocytosis and other biological phenomena.

PMID- 11841940
TI  - Expression analysis of the tylosin-biosynthetic gene cluster: pivotal regulatory
      role of the tylQ product.
AB  - Expression analysis by RT-PCR, applied to the entire tyl cluster, revealed that
      the pattern of transcription is more complex than expected. For example, the five
      tylG polyketide synthase genes are not necessarily cotranscribed or even
      coregulated. Among the regulatory genes, tylQ has emerged as a key factor.
      Although several genes (including the positive regulator, tylS) were possibly
      expressed constitutively, only tylQ was silent during secondary metabolism.
      Analysis of engineered strains, in which tylQ was disrupted or overexpressed,
      showed that the TylQ protein is a transcriptional repressor that blocks tylosin
      biosynthesis by controlling expression of the activator, tylR. Before tylosin
      production can be triggered, tylQ must be switched off, or at least
      downregulated.

PMID- 11841941
TI  - Hepatitis C virus NS3 protease requires its NS4A cofactor peptide for optimal
      binding of a boronic acid inhibitor as shown by NMR.
AB  - NMR spectroscopy was used to characterize the hepatitis C virus (HCV) NS3
      protease in a complex with the 24 residue peptide cofactor from NS4A and a
      boronic acid inhibitor, Ac-Asp-Glu-Val-Val-Pro-boroAlg-OH. Secondary-structure
      information, NOE constraints between protease and cofactor, and hydrogen
      deuterium exchange rates revealed that the cofactor was an integral strand in the
      N-terminal beta-sheet of the complex as observed in X-ray crystal structures.
      Based upon chemical-shift perturbations, inhibitor-protein NOEs, and the
      protonation state of the catalytic histidine, the boronic acid inhibitor was
      bound in the substrate binding site as a transition state mimic. In the absence
      of cofactor, the inhibitor had a lower affinity for the protease. Although the
      inhibitor binds in the same location, differences were observed at the catalytic
      site of the protease.

PMID- 11841942
TI  - Effects of novel taxanes SB-T-1213 and IDN5109 on tubulin polymerization and
      mitosis.
AB  - SB-T-1213 and IDN5109 are semisynthetic, orally available taxanes that are up to
      400-fold more active than paclitaxel against drug-resistant cells. IDN5109 is in
      clinical trials. We investigated the primary target for SB-T-1213 and IDN5109 and
      whether the compounds interact with microtubules differently than paclitaxel.
      Unlike paclitaxel, at 1-10 microM both novel taxanes initiate microtubule
      polymerization in vitro with no lag. They enhance polymerization equally or more
      potently than paclitaxel. SB-T-1213 induces unusual microtubules with attached
      extra protofilaments or open sheets, and IDN5109 induces large protofilamentous
      sheets. Both inhibit HeLa cell proliferation, block mitosis at the
      metaphase/anaphase transition, bundle microtubules at high drug concentrations,
      and induce abnormal metaphase spindles and apoptosis. They target microtubules
      but alter their polymerization and structure differently than paclitaxel. These
      differences may play a role in their enhanced cytotoxicity and efficacy.

PMID- 11841943
TI  - Formation of beta-hydroxy histidine in the biosynthesis of nikkomycin
      antibiotics.
AB  - Nikkomycins, a group of peptidyl nucleoside antibiotics produced Streptomyces
      tendae Tu901, are potent competitive inhibitors of chitin synthase. In this
      study, three nikkomycin biosynthetic enzymes, NikP1, NikQ, and NikP2, were
      overexpressed, purified, and characterized. The NikP1 activated L-His and
      transferred it to the carrier protein domain to form L-His-S-NikP1, which served
      as the beta-hydroxylation substrate of NikQ. The beta-OH-His was then
      hydrolytically released from NikP1 by NikP2. The results reported here
      substantiate our earlier proposal that the covalent tethering of an amino acid
      onto a carrier protein domain prior to downstream modification is a general
      strategy for diverting a fraction of the amino acid into secondary metabolism.

PMID- 11841944
TI  - An inhibitor of the human UDP-GlcNAc 4-epimerase identified from a uridine-based
      library: a strategy to inhibit O-linked glycosylation.
AB  - The biological study of O-linked glycosylation is particularly problematic, as
      chemical tools to control this modification are lacking. An inhibitor of the UDP
      GlcNAc 4-epimerase that synthesizes UDP-GalNAc, the donor initiating O-linked
      glycosylation, would be a powerful reagent for reversibly inhibiting O-linked
      glycosylation. We synthesized a 1338 member library of uridine analogs directed
      to the epimerase by virtue of substrate mimicry. Screening of the library
      identified an inhibitor with a K(i) value of 11 microM. Tests against related
      enzymes confirmed the compound's specificity for the UDP-GlcNAc 4-epimerase.
      Inhibitors of a key step of O-linked glycan biosynthesis can be discovered from a
      directed library screen. Progeny thereof may be powerful tools for controlling O
      linked glycosylation in cells.

PMID- 11841945
TI  - Precursor-directed biosynthesis: biochemical basis of the remarkable selectivity
      of the erythromycin polyketide synthase toward unsaturated triketides.
AB  - The structural basis for the striking stereochemical discrimination among
      triketide analogs has been investigated by incubating a series of N-acetyl
      cysteamine (-SNAC) esters of unsaturated triketides with DEBS module 2+TE. The
      triketide analogs were first screened under a standard set of short-term
      incubation conditions in the presence of the extender substrate methylmalonyl-CoA
      and NADPH. For those triketide analogs that served as substrates for module 2+TE,
      the relative specificity, represented by the k(cat)/K(M) values, was quantitated.
      Triketide diastereomers that were converted in precursor-directed biosynthesis
      experiments to unsaturated 16-membered ring macrolides by DEBS(KS1(0)) were good
      to excellent substrates for DEBS module 2+TE, whereas analogs that were converted
      to the 14-membered ring analogs of 10,11-dehydro-6-deoxyerythronolide B by
      DEBS(KS1(0)) were not turned over at all by module 2+TE.

PMID- 11841946
TI  - Metabolic mapping with bioluminescence: basic and clinical relevance.
AB  - This review is focused on metabolic mapping in biological tissue with
      quantitative bioluminescence and single photon imaging. Metabolites, such as ATP,
      glucose and lactate, can be imaged quantitatively and within microscopic
      dimensions in cryosections from shock frozen biological specimens using enzyme
      reactions and light emission by luciferases. The technique has been applied in
      numerous targets and models of experimental biomedical research, such as
      multicellular spheroids, various organs of laboratory animals in a physiological
      or pathophysiological state, and even in plant seeds. Among numerous other
      aspects, data obtained with this method have contributed to the elucidation of
      mechanisms that are involved in the development of necrosis in multicellular
      spheroids. The combination of the bioluminescence technique with
      immunohistochemistry, autoradiography or in situ hybridization can considerably
      reduce ambiguities in the interpretation of the experimental results. Although,
      an invasive technique, bioluminescence imaging has been used most intensively in
      clinical oncology using tumor biopsies taken at the first diagnosis of the
      disease. It has been shown for squamous cell carcinomas of the head and neck and
      of the uterine cervix that accumulation of high levels of lactate in the primary
      lesions is associated with a high risk of metastasis formation and a reduced
      overall and disease-free patient survival. Thus, metabolic imaging can provide
      additional information on the degree of malignancy and the prognosis of tumors
      which may help the oncologist in improving specific treatment approaches for each
      individual malignant disease. Last but not least, metabolic mapping in clinical
      oncology has stimulated a number of investigations in basic cancer research on
      mechanisms that underlie the correlation between tumor metabolism and malignancy.

PMID- 11841947
TI  - In vitro and in silico analysis of the predicted human MOB gene encoding a
      phylogenetically conserved transmembrane protein.
AB  - A novel evolutionary conserved human MOB gene of seven exons is predicted on the
      chromosome 10. MOB is supposed to express predominately in brain. At least three
      types of MOB transcripts are proposed. A protein encoded by MOB is five-pass
      transmembrane molecule.

PMID- 11841948
TI  - Recognition of cell-specific binding of phage display derived peptides using an
      acoustic wave sensor.
AB  - ASSLNIA, a peptide selected for murine myofibers using phage display technology,
      was immobilized onto an acoustic wave sensor. The sensor responded to murine and
      feline muscle homogenates indicating crosspieces interactions. Kidney, liver, and
      brain preparations produced insignificant responses.

PMID- 11841949
TI  - Comparison of two fluorescence immunoassay methods for the detection of endocrine
      disrupting chemicals in water.
AB  - We describe two fluorescence immunoassays capable of detecting endocrine
      disrupting compounds in waste water. The first fluorescence method is a
      heterogeneous assay using total internal reflection fluorescence (TIRF)
      detection. The second method is a homogeneous assay that utilizes energy transfer
      (ETIA). Both fluorescence immunoassays are compared with respect to detection
      principle and ability to quantify the model analytes estrone, estradiol, and
      ethinylestradiol in a complex matrix regarding recovery rates and limits of
      detection. Calibrations were performed for the three analytes using both
      fluorescence methods. Limits of detection between 0.01 and 0.85 microg/l are
      achieved. In addition, measurements in synthetic waste water spiked with the
      analytes were performed. Both immunoassays allow the detection in waste water
      with recovery rates in the range of 70-112%.

PMID- 11841952
TI  - Type 2 diabetes mellitus in adolescents.
AB  - While diabetes mellitus types 1 and 2 used to be distinguished largely by age at
      onset, in the past decade there has been an increase in the number of children
      presenting with diabetes that can be controlled with oral medications. This has
      lead to these children being diagnosed with type 2 diabetes mellitus despite
      their young age. This chapter offers an overview of presenting features,
      pathophysiology, treatment and prognosis of this disorder in the adolescent
      patient. Additionally, it offers information regarding the relationship between
      increasing childhood obesity and a rise in the reported cases of diabetes in
      children. Appropriate screening and laboratory tests and their results are
      explained, and the pros and cons of both pharmacologic and non-pharmacologic
      therapies are discussed. Some complications of diabetes in the developing
      adolescent differ from those adults will face, and the well-known complications
      of diabetes (hyperlipidemia, hypertension) must be addressed in a population that
      is not normally screened for these health concerns. It is hoped that by educating
      physicians to the potential for this disorder in their adolescent patients, long
      term complications can be reduced and advanced sequelae of vascular and
      neurologic problems can possibly be avoided altogether.

PMID- 11841950
TI  - Phylogenetic relationships and genetic polymorphisms in wild Indian mice.
AB  - Randomly amplified polymorphic DNA (RAPD) analysis was used to examine the extent
      of variability in 11 Indian wild derived commensal house mice (Mus musculus)
      populations and compared with inbred strains of musculus and domesticus
      subspecies as well as commonly used laboratory inbred strains C57BL/6J and
      DBA/2J. Arbitrary designed 10 mer oligonucleotide primers with 60-70% (G+C)
      content were used to amplify DNA template. Out of 52 primers screened initially
      on the laboratory strains, 20 were selected for analysis on the basis of
      amplification product in the size range of 200-1400 bp. Among 353 total
      polymorphic bands, 220 bands (64%) were found to be polymorphic in Indian wild
      mice, 85 bands (25%) in wild derived inbred strains and 37 bands (11%) in
      laboratory mice strains. The amplification patterns produced by primers were
      statistically analysed by Jaccard's similarity coefficient the value of which
      ranged from 0.56 to 0.80. High level of genetic diversity was seen in the Indian
      wild mice populations as compared to the controls. The UPGMA phenogram grouped
      mice population into two major clusters except Bikaner [BIK], Bilaspur [BIL] and
      Ranikhet [RK] populations which were placed outside the close-knit clusters.
      Inspite of low values of bootstrap estimates obtained by Wagner and Dollo
      parsimony analysis, the results were comparable with UPGMA phenogram when
      constitution of the populations in the major cluster was considered. Indian mice
      populations appeared to be diverse from laboratory inbred mice strains.

PMID- 11841953
TI  - Adolescent thyroid disorders.
AB  - Thyroid disorders are common in adolescence. Thyroid nodules can present in this
      age group, and although most are benign, malignancy is not unheard of. Chronic
      lymphocytic thyroiditis can present as hypothyroidism, while the adolescent with
      a goiter due to autoimmune thyroid disease is frequently euthyroid. Graves
      disease is a common etiology of hyperthyroid presentation in this age group.
      While there are known genetic and iatrogenic conditions that may predispose
      thyroid problems, they may also happen randomly in the general population.
      Thyroid problems may present as a goiter, a nodule, or a general cluster of
      abnormal symptoms and physical findings. The unique challenge to the provider of
      adolescent health care is that thyroid problems can adversely affect growth and
      development during puberty, a crucial period of hormonal interaction. This
      chapter addresses the diagnosis, treatment alternatives, and prognosis for a
      variety of common and uncommon thyroid abnormalities in adolescents. Many are
      readily treatable if recognized promptly, and even thyroid cancer often can be
      effectively treated and managed. Physicians treating the adolescent population
      have to be aware of the various thyroid problems that their patients can face.

PMID- 11841954
TI  - Hyperlipidemia in adolescents.
AB  - Coronary artery disease is the leading cause of morbidity and mortality in the
      United States. Studies increasingly indicate that atherosclerotic lesions are
      evident in the vasculature by late adolescence, and that hyperlipidemias are a
      common and remediable contributor to their development. Hence, health care
      providers dealing with adolescents must be familiar with contemporary concepts
      about the etiology, classification, and management of hyperlipidemias in children
      and adolescents. This chapter briefly reviews lipid metabolism, emphasizing
      lipoprotein composition, key components, enzymes, cellular receptors, transport,
      uptake, and fate. This framework provides a rational classification with
      exclusion and treatment of secondary causes such as obesity, poorly controlled
      diabetes, hypothyroidism, and oral contraceptive therapy, followed by currently
      recommended approaches to the primary hyperlipidemias, which affect at least
      1:500 persons. Guidelines for screening adolescents at risk and incremental
      treatment with diet and lipid-lowering medications, including  statins,  are
      reviewed in the context of current national recommendations.

PMID- 11841955
TI  - Bone strength and the adolescent.
AB  - The strength of adult bone reflects factors that regulate bone quality
      (architecture) and density (bone mass or quantity of calcium deposited/unit of
      bone) acquired during childhood and adolescence. Near-maximal or peak bone mass
      of the vertebrae and femurs is achieved at the completion of pubertal
      development. Because inexorable loss of bone mass begins in mid-adulthood in
      normal people, the magnitude of peak bone mass determines individual risk for
      later development of osteopenia and osteoporosis--disorders of compromised bone
      strength that lead to bone fragility and increased fracture risk. Osteoporosis is
      a disabling and costly disease with a high mortality rate; one in five patients
      with an osteoporotic fracture dies within 1 year of sustaining the fracture.
      Fifty percent of maximal peak bone mass is accumulated during puberty in normal
      people who have adequate intake of calcium (1300 mg/day), vitamin D (400 U/day),
      and other macro- and micro-nutrients but avoid excessive weight gain, undertake
      appropriate weight-bearing exercises (walking, jumping, hopping), secrete normal
      amounts of sex hormones (androgen and estrogen) and growth hormone, limit
      ingestion of cola beverages, and avoid alcohol intake and smoking. This chapter
      reviews the regulation of bone development in adolescents and the factors that
      positively or adversely affect this process.

PMID- 11841957
TI  - Hyperandrogenism in adolescents.
AB  - Signs and symptoms of excessive androgen secretion (hyperandrogenism) in
      adolescent and adult women include hirsutism, severe acne, and irregular menses.
      Because of the clinical features associated with hyperandrogenism, male
      adolescents do not usually present with signs or symptoms of androgen excess.
      This chapter focuses on causes of hyperandrogenism in adolescents, especially
      adolescent girls, including disorders of steroidogenesis, gonadal dysgenesis,
      Cushing's syndrome, tumors, and glucocorticoid resistance. Because polycystic
      ovary syndrome is discussed thoroughly in another chapter, it is not included.
      Brief discussions of androgen metabolism and steroidogenesis are followed by
      particulars of specific disorders. The chapter concludes with suggestions about
      differential diagnoses.

PMID- 11841956
TI  - Polycystic ovary syndrome in adolescents.
AB  - Recent findings suggest substantial metabolic sequelae to polycystic ovary
      syndrome (PCOS), including risk of diabetes and cardiovascular disease. Primary
      treatment of the metabolic sequelae should be the focus of the clinician. The
      definition of PCOS has been expanded from a disorder that presents at menarche
      and ends at menopause to a disorder that may be present from birth to senescence.
      The earliest recognized PCOS phenotype to date is premature pubarche
      characterized by excessively elevated levels of dehydroepiandosterone sulfate and
      hyperinsulinemia. Such girls are at high risk to develop the full PCOS phenotype,
      including ovarian hyperandrogenism and chronic anovulation. A fasting glucose-to
      insulin ratio of < 7 is a useful index of insulin resistance in adolescents.
      However, each patient should be evaluated for glucose intolerance and lipid
      abnormalities on a regular basis by completing a 2-hour oral glucose tolerance
      test and a fasting lipid profile. Primary prevention of diabetes and
      cardiovascular disease by lifestyle modifications, regular exercise, and a
      balanced diet are of utmost importance, especially in adolescents who have the
      opportunity to establish healthy habits before entering adulthood. The role of
      insulin-sensitizing medications is still under study. Although no clinical trials
      over 6 months in duration have assessed the long-term efficacy of metformin use
      in adolescents, short-term trials have shown promising effects in lowering
      insulin secretion, improving insulin sensitivity, restoring normal menstrual
      cycles, and correcting lipid abnormalities.

PMID- 11841958
TI  - Delayed puberty.
AB  - Normal puberty is a time of life and a process of development that results in
      full adult maturity of growth, sexual development, and psychosocial achievement.
      Delayed puberty describes the clinical condition in which the pubertal events
      start late (usually > +2.5 SD later than the mean) or are attenuated in
      progression. The differential diagnosis includes syndromes of low gonadotropin
      production, usually constitutional delay of growth and maturation associated with
      chronic disease, but also an array of gene-mediated disorders, and syndromes of
      primary gonadal dysfunction with hypergonadotropic hypogonadism, including Turner
      and Klinefelter syndromes, and a group of acquired and genetic abnormalities.
      Diagnostic assessment and varied therapeutic modalities are discussed. The issues
      of androgen or estrogen therapy are important to assess, and growth hormone
      treatment remains a difficult dilemma.

PMID- 11841959
TI  - Gender identity/role differentiation in adolescents affected by syndromes of
      abnormal sex differentiation.
AB  - Adolescents with abnormal sexual differentiation or intersex conditions present a
      unique challenge to their healthcare providers. While  sex  refers to the
      biologic considerations that specify a person as male or female,  gender  refers
      to the sex of rearing. For the child with an intersex condition, sex may differ
      from gender, and as that child grows into adolescence, this may lead to many
      concerns, questions, and decisions. Although gender is usually fixed by
      adolescence, there will be those adolescents with intersex conditions wishing a
      gender reassignment during this period. Often a physician is the best resource
      for information and counsel to these young adults. Although most infants with
      ambiguous genitalia will have a karyotype done to determine gender identity,
      there are occasions when a gender discrepancy is not noticed until an adolescent
      presents with delayed pubarche. Regardless of the age at diagnosis, at
      adolescence, the physician must the address the medical consequences of
      infertility, bone health, and hormone replacement in addition to handling the
      heightened psychological concerns of gender identity during puberty. It is hoped
      that adolescents with intersex conditions will have the support and information
      necessary to allow them to live as normal a life as possible.

PMID- 11841960
TI  - Endocrine aspects of eating disorders in adolescents.
AB  - Eating disorders are an important health concern among adolescents. Young women
      frequently present with signs and symptoms of anorexia nervosa and bulimia
      nervosa. These disorders represent clinically significant illnesses with serious
      and sometimes permanent medical complications, including a number of endocrine
      conditions, that, in general, result from the body s adaptive response to
      malnutrition. Examples include disorders of metabolism, cortisol and leptin
      regulation, fluid and electrolyte homeostasis, thyroid function, glucose
      regulation, growth and development, and reproductive function with the
      development of amenorrhea as well as the risk of osteoporosis.

PMID- 11841961
TI  - Endocrine complications of cystic fibrosis.
AB  - Patients with cystic fibrosis (CF) are now living longer, with a median survival
      of 32 years in 2000. With longer life expectancy and improved treatments for
      pulmonary disease, other complications of CF are becoming more apparent. The
      primary endocrine complications affecting adolescents with CF include (1) poor
      growth and pubertal development, (2) CF-related diabetes, and (3) poor bone
      mineralization. This chapter discusses pathophysiology, screening, and treatment
      of endocrine complications of CF.

PMID- 11841962
TI  - Endocrine sequelae in survivors of childhood cancer.
AB  - Long-term survival after treatment for childhood cancers has dramatically
      improved in the past 25 years. Overall 5-year survival rates for childhood cancer
      are greater than 70%. Residual endocrine disorders are as high as 40% in this
      population, with the most serious disturbances noted in growth and thyroid
      function. Dysfunction also is observed in the hypothalamic-pituitary-adrenal axis
      and the hypothalamic-pituitary-gonadal axis, and recent evidence cites
      alterations in bone and mineral metabolism, body composition, and lipid
      disorders. These abnormalities are most likely related directly to prior cancer
      treatment. This chapter focuses on a description of such disorders and offers
      suggestions for long-term endocrine management and follow-up evaluation.

PMID- 11841963
TI  - Genital size: a common adolescent male concern.
AB  - Long before adolescence, males hear insinuations about adequacy of penis size.
      This concern may heighten during teen years and persist to varying degrees into
      adulthood. Men tend to underestimate their own penis size. This chapter provides
      objective information about anatomy and growth of the penis, including data about
      normal sizes. Published data indicate that, although full growth may be reached
      at different ages during adolescence, size is similar for most adult males.
      Hopefully, this information will provide the basis for teenaged males to develop
      a healthy perspective and to avoid intimidation by unfounded claims about sexual
      enhancement or size enlargement techniques.

PMID- 11841964
TI  - Obesity in the adolescent.

PMID- 11841967
TI  - Clinical trials of intercessory prayers?

PMID- 11841968
TI  - Capitalizing on women's intellectual capital in the professions.

PMID- 11841969
TI  - Mission-based management and the improvement of medical students' education.

PMID- 11841970
TI  - How do medical schools use measurement systems to track faculty activity and
      productivity in teaching?
AB  - The authors describe their findings from a study that (1) identified 41 medical
      schools or medical school departments that used metric systems to quantify
      faculty activity and productivity in teaching and (2) analyzed the purposes and
      progress of those systems. Among the reasons articulated for developing these
      systems, the most common was to identify a "rational" method for distributing
      funds to departments. More generally, institutions wanted to emphasize the
      importance of the school's educational mission. The schools varied in the types
      of information they tracked, ranging from a selective focus on medical school
      education to a comprehensive assessment of teaching activity and educational
      administration, committee work, and advising. Schools were almost evenly split
      between those that used a relative-value-unit method of tracking activity and
      those that used a contact-hour method. This study also identified six challenges
      that the institutions encountered with these metric systems: (1) the lack of a
      culture of data in management; (2) skepticism of faculty and chairs; (3) the
      misguided search for one perfect metric; (4) the expectation that a metric system
      will erase ambiguity regarding faculty teaching contributions; (5) the lack of,
      and difficulty with developing, measures of quality; and (6) the tendency to
      become overly complex. Because of the concern about the teaching mission at
      medical schools, the number of institutions developing educational metric systems
      will likely increase in the coming years. By documenting and accounting
      financially for teaching, medical schools can ensure that the educational mission
      is valued and appropriately supported.

PMID- 11841971
TI  - Mission aligned management and allocation: a successfully implemented model of
      mission-based budgeting.
AB  - In response to declining funding support and increasing competition, medical
      schools have developed financial management models to assure that resource
      allocation supports core mission-related activities. The authors describe the
      development and implementation of such a model at the University of Wisconsin
      Medical School. The development occurred in three phases and included consensus
      building on the need for mission-based budgeting, extensive faculty involvement
      to create a credible model, and decisions about basic principles for the model.
      While each school may encounter different constraints and opportunities, the
      authors outline a series of generic issues that any medical school is likely to
      face when implementing a mission-based budgeting model. These issues include
      decisions about the amounts and sources of funds to be used in the budgeting
      process, whether funds should be allocated at the department or individual
      faculty level, the specific metrics for measuring academic activities, the
      relative amounts for research and teaching activities, and how to use the budget
      process to support new initiatives and strategic priorities. The University of
      Wisconsin Medical School's Mission Aligned Management and Allocation (MAMA) model
      was implemented in 1999. The authors discuss implementation issues, including
      timetable, formulas used to cap budget changes among departments during phase-in,
      outcome measures used to monitor the effect of the new budget model, and a
      process for school-wide budget oversight. Finally, they discuss outcomes tracked
      during two years of full implementation to assess the success of the new MAMA
      budget process.

PMID- 11841972
TI  - Creating a mission-based reporting system at an academic health center.
AB  - The authors developed a Web-based mission-based reporting (MBR) system for their
      university's (UC Davis's) health system to report faculty members' activities in
      research and creative work, clinical service, education, and community/university
      service. They developed the system over several years (1998-2001) in response to
      a perceived need to better define faculty members' productivity for faculty
      development, financial management, and program assessment. The goal was to create
      a measurement tool that could be used by department chairs to counsel faculty on
      their performances. The MBR system provides measures of effort for each of the
      university's four missions. Departments or the school can use the output to
      better define expenditures and allocations of resources. The system provides both
      a quantitative metric of times spent on various activities within each mission,
      and a qualitative metric for the effort expended. The authors report the process
      of developing the MBR system and making it applicable for both clinical and basic
      science departments, and the mixed success experienced in its implementation. The
      system appears to depict the activities of most faculty fairly accurately, and
      chairs of test departments have been generally enthusiastic. However, resistance
      to general implementation remains, chiefly due to concerns about reliability,
      validity, and time required for completing the report. The authors conclude that
      MBR can be useful but will require some streamlining and the elimination of other
      redundant reporting instruments. A well-defined purpose is required to motivate
      its use.

PMID- 11841973
TI  - Academic medicine and the search for meaning and purpose.
AB  - The transformation of the health care industry into a marketplace governed by
      commercialism and free competition challenges the doctrine of medicine as a
      profession valuing service to the patient above financial reward. Many physicians
      have become disenchanted with their ability to serve as advocates for and provide
      care to their patients. Financial success, the measure of the marketplace, has
      become the dominant standard of measurement or "value" for most academic medical
      centers (AMCs). Many doctors report their work is less fulfilling. As a result,
      all three social missions-patient care, teaching, and research-are in jeopardy.
      The growth of modernism, preeminence of biomedical research, and dominance of a
      market-driven clinical enterprise will continue to pose challenges to the health
      care system in the United States. However, AMCs can provide the leadership and
      serve as the ambassadors through which the health care system can be renewed with
      a sense of direction and purpose. Renewal must begin with more open discourse
      about what we value in health care and what kind of medical profession we want to
      have, to include addressing questions such as: What does it mean to be an
      academic physician? What gives my work meaning and purpose? This kind of dialogue
      could easily be built into the medical students' curricula and residency training
      programs, with the faculty taking the lead.

PMID- 11841976
TI  - The use of constrained optimization to facilitate admission decisions.
AB  - Weighting models do not adequately represent admission goals. A constrained
      optimization (CO) decision-analysis model is an alternative that allows a more
      useful and accurate translation of goals in the admission process. CO allows easy
      translation of class composition objectives into the model. The author used
      simulated data to demonstrate the CO technique within a medical-school-admission
      context. Variables related to class diversity and individual achievement were
      used to select a class from a simulated final applicant pool. Constraints in the
      model were evaluated for their effects on the class. The model performed well and
      yielded significant advantages over weighting equations.

PMID- 11841975
TI  - Arrogance among physicians.
AB  - Arrogance among physicians is, regrettably, common and violates the benevolent
      spirit of medicine-its very soul -as well the quality of medical care. The need
      for humility in the physician warrants greater emphasis in medical training, both
      in the classroom and, more critically, by example. Arrogance persists because of
      intersecting and mutually enhancing sociologic and psychological pressures.
      Regarding the sociologic elements, in earlier times, the great respect and
      prestige accorded physicians could foster arrogance in some. Today, physicians as
      a group are less likely to be idealized, but the health care system has
      depersonalized the doctor-patient relationship and created a kind of "system
      arrogance" in which the patient is seen not as a person but merely as a job to be
      done cost-effectively. As for psychological aspects, physicians are sometimes
      drawn to medicine by their unconscious concerns about illness and mortality-they
      become health experts in the hope of extending their own lives. Such physicians
      treat death as the enemy, and may practice unwarranted heroic measures. But the
      most critical variable in the development of arrogance is a physician's knowledge
      and thereby his or her power over the patient. This can delude some physicians
      into imagining that they are all-powerful. Seriously ill or injured patients tend
      to view the physician as an omnipotent parent and savior, and in this way
      unwittingly tempt physicians to be arrogant. The author concludes by reminding
      his fellow physicians that "we should not exaggerate our own importance. we are
      but an instrument of healing and not its source."

PMID- 11841977
TI  - The clinical skills laboratory: a cost-effective venue for teaching clinical
      skills to third-year medical students.
AB  - The authors taught clinical examination and procedural skills using manikins in a
      clinical skills laboratory as a part of an integrated curriculum in the third
      year clerk-ship. This teaching modality was effective and well received by
      students and faculty.

PMID- 11841981
TI  - The quality of in-house medical school examinations.
AB  - PURPOSE: Most medical schools test their students throughout the curriculum using
      in-house examinations written by the faculty who teach the courses. The authors
      assessed the quality of in-house examinations used in three U.S. medical schools.
      METHOD: In 1998, nine basic science examinations from the three schools were
      gathered and each question was subjected to quality assessment by three expert
      biomedical test developers, each of whom has had extensive experience in
      reviewing and evaluating questions for the United States Medical Licensing
      Examination (USMLE) Steps 1 and 2. Questions were rated on a five-point scale: 1
      = tested recall only and was technically flawed to 5 = used a clinical or
      laboratory vignette, required reasoning to answer, and was free of technical
      flaws. Each rater made independent assessments, and the mean score for each
      question was calculated. Mean quality scores for National Board of Medical
      Examiners (NBME) who were trained question writers were compared with the mean
      scores for question writers without NBME training. The raters' quality
      assessments were made without knowledge of the test writers' training background
      or the study's hypothesis. RESULTS: A total of 555 questions were analyzed. The
      mean score for all questions was 2.39 +/- 1.21. The 92 questions written by NBME
      trained question writers had a mean score of 4.24 +/- 0.85, and the 463 questions
      written by faculty without formal NBME training had a mean score of 2.03 +/- 0.90
      (p <.01). CONCLUSIONS: The in-house examinations were of relatively low quality.
      The quality of examination questions can be significantly improved by providing
      question writers with formal training.

PMID- 11841982
TI  - Making sense of trying not to teach: an interview study of tutors' ideas of
      problem-based learning.
AB  - PURPOSE: To explore how a cohort of first-ever "foundation" tutors in a new
      problem-based curriculum characterized and made sense of problem-based learning
      (PBL). METHOD: The sample consisted of all foundation tutors (n = 34) from The
      University of Liverpool's undergraduate medical curriculum, 1996-97, the first
      semester of the first year that PBL became a main vehicle for knowledge
      acquisition. The cross-sectional study design involved semistructured telephone
      interviews with the tutors about PBL and problem solving. The author taped and
      transcribed the interviews and conducted an inductive analysis of these
      qualitative data. RESULTS: All tutors responded, with interviews lasting about 20
      minutes: 26/34 (76%) were men and 23 (68%) were medically qualified. Twenty-nine
      (85%) facilitated 19-21 of the 21 PBL sessions. Most tutors conceptualized PBL as
      being student-centered (68%), involving small-group work (53%), but ignored its
      reflective component. They conceptualized good PBL tutors diversely, but mostly
      as "knowing" when and how to intervene (41%) and empathizing with students (29%).
      Few tutors characterized PBL in terms of problem solving, yet over half agreed,
      cursorily, that they were intimately related. The tutors were generally unclear
      about this relationship. CONCLUSION: These tutors mostly characterized PBL
      positively as a philosophy, yet missed its reflective elements and were
      particularly challenged by their own fallibility in knowing when and how to
      intervene without teaching. Internal motivation and direct experience of PBL
      helped balance some of the tutors' confusion with the educational rationale,
      highlighting possibilities for future staff development.

PMID- 11841983
TI  - Academic ranks and medical schools of underrepresented minority faculty in family
      medicine departments.
AB  - PURPOSE: To examine academic rankings and educational backgrounds of
      underrepresented minority (URM) family medicine faculty and compare their
      academic ranks with national trends. The authors also determined the extent to
      which international and historically black educational institutions contributed
      URM faculty to family medicine. METHOD: In 1999 questionnaires were sent to 129
      family medicine departments asking for academic ranks and educational
      institutions attended by their URM faculty. Comparisons were made between URM
      faculty's academic ranks and all family medicine faculty, medical school minority
      faculty, and medical school faculty. RESULTS: A total of 80% of URM faculty were
      assistant professors or instructors, and 4.4% were professors. URM family
      medicine faculty had significantly lower rankings compared with medical school
      minority faculty and all family medicine faculty. URM family medicine faculty at
      historically black medical schools were more likely to have received their
      degrees from historically black undergraduate institutions and medical schools
      than were URM family medicine faculty at non-historically-black medical schools.
      CONCLUSIONS: URM family medicine faculty appear to experience a double
      disadvantage: being minority and working for family medicine departments. Their
      academic ranks remain far below those of both minority medical school faculty and
      family medicine faculty, a discouraging finding considering the current shortage
      of URM faculty in family medicine departments. Historically black medical schools
      cannot address the shortage alone, so non-historically-black medical schools need
      to both recruit URM faculty and follow up with appropriate mentoring of those
      faculty.

PMID- 11841985
TI  - Validation of a global measure of faculty's clinical teaching performance.
AB  - PURPOSE: To validate the University of Michigan Global Rating Scale (GRS), a
      single-item, five-point global measure of faculty members' clinical teaching
      performances previously shown to be reliable. METHOD: In June 1998, 98 senior
      medical residents (98% of seniors) from four academic institutions completed the
      GRS for all teaching faculty at their institutions. Each resident also completed
      the 26-item Stanford Faculty Development questionnaire (SFDP26) for ten faculty
      with whom he or she had had teaching contact during residency. The SFDP26 is a
      validated instrument that measures seven specific aspects of clinical teaching
      (e.g., communication of goals, feedback). RESULTS: The mean GRS score (SE) was
      3.83 (.07). There was no difference in mean GRS or SFDP26 subscale scores across
      institutions. In a random-effects model that controlled for interrater
      reliability, correlation coefficients comparing the mean GRS scores and the mean
      scores for the individual SFDP26 subscales ranged from.86 to.98. CONCLUSIONS: The
      GRS correlates highly with measures of seven specific aspects of teaching
      effectiveness among senior medical residents. The GRS is a simple, readily
      administered measure of faculty's teaching performances that can be used by
      residency programs as part of an incentive or reward program, to identify
      teachers as potential candidates for faculty development, or for consideration in
      promotion decisions.

PMID- 11841987
TI  - Informed consent and patient videotaping.
AB  - PURPOSE: To determine whether videotaping consent forms used in family medicine
      residencies meet the criteria for informed consent, adhere to published
      guidelines for videotaping patients, and are written at a suitable reading level.
      METHOD: Three reviewers independently evaluated videotaping consent forms
      obtained from 20 family practice residencies to determine whether they included
      the elements of informed consent and conformed to published guidelines for
      ethical videotaping. The reading level of each consent form was also determined
      using a standardized assessment. RESULTS: Depending on the reviewer, only one to
      three of the 20 consent forms were judged adequate in providing a patient with
      enough information to make an informed choice. Specific aspects of voluntariness
      were absent from most of the forms. In addition, the reading level was, on
      average, well above recommended levels for patient comprehension. CONCLUSION:
      Most of the videotaping consent forms analyzed in this study did not provide
      adequate information to assist patients in making a voluntary, informed choice to
      be videotaped. The absence of this information raises the potential for
      violations of patient privacy and confidentiality.

PMID- 11841988
TI  - Medical students' occupational exposures to potentially infectious agents.
AB  - PURPOSE: To describe the epidemiology of occupational exposures sustained by
      third-year medical students at a state university medical school, and identify
      associated factors that may be modified to decrease exposure risk. METHOD: The
      cohort consisted of all third-year students after completion of each third-year
      clerkship rotation. At the end of each clinical rotation (a total of six for each
      student during the year), questionnaires were distributed to the 119 students.
      Demographic information, type of exposure, rotation, circumstances, compliance
      with CDC universal precaution recommendations, and post-exposure prophylaxis
      (PEP) were assessed. Inferential statistics were used to describe the results.
      RESULTS: Of a total of 714 questionnaires, 644 (90.2%) were returned. Of the 644,
      there were 60 reports (9.3%) of one or more exposures to blood or body fluids.
      The incidence of exposure varied with clerkship: 23 on surgery, 18 on obstetrics
      gynecology, eight on outpatient medicine, four on psychiatry, four on pediatrics,
      and three on internal medicine. Thirty-six (60%) were skin or mucous membrane
      exposures to blood, body fluid, or respiratory secretions, and 24 (40%) were
      percutaneous exposure by instrument. Ten (17%) of the exposures resulted in
      official incident reports and seven accepted PEP recommendations. CONCLUSION:
      Medical students are often exposed to body fluids during their initial clerkship
      year, primarily in their surgical rotations. Additional education on these
      rotations may be useful in reducing exposure risk.

PMID- 11841989
TI  - Cutting-edge technology. I. Global gene expression profiling using DNA
      microarrays.
AB  - Having the complete human genomic sequence poses a new challenge: to use genomic
      structural information to display and analyze biological processes on a genome
      wide scale to assign gene function. DNA microarrays are a miniaturized, ordered
      arrangement of nucleic acid fragments from individual genes located at defined
      positions on a solid support, enabling the analysis of thousands of genes in
      parallel by specific hybridization. This review describes technical aspects,
      discusses relevant applications, and suggests factors affecting the use of this
      technology and how it fits in the grand scheme of meeting the needs of the
      postgenomic era.

PMID- 11841990
TI  - Physiology of iron transport and the hemochromatosis gene.
AB  - Iron is essential for fundamental cell functions but is also a catalyst for
      chemical reactions involving free radical formation, potentially leading to
      oxidative stress and cell damage. Cellular iron levels are therefore carefully
      regulated to maintain an adequate substrate while also minimizing the pool of
      potentially toxic "free iron." The main control of body iron homeostasis in
      higher organisms is placed in the duodenum, where dietary iron is absorbed,
      whereas no controlled means of eliminating unwanted iron have evolved in mammals.
      Hereditary hemochromatosis, the prototype of deregulated iron homeostasis in
      humans, is due to inappropriately increased iron absorption and is commonly
      associated to a mutated HFE gene. The HFE protein is homologous to major
      histocompatibility complex class I proteins but is not an iron carrier, whereas
      biochemical and cell biological studies have shown that the transferrin receptor,
      the main protein devoted to cellular uptake of transferrin iron, interacts with
      HFE. This review focuses on recent advances in iron research and presents a model
      of HFE function in iron metabolism.

PMID- 11841991
TI  - N(omega)-nitro-L-arginine inhibits inducible HSP-70 via Ca(2+), PKC, and PKA in
      human intestinal epithelial T84 cells.
AB  - The nitric oxide (NO) synthase inhibitor N(omega)-nitro-L-arginine (L-NNA)
      inhibits heat stress (HS)-induced NO production and the inducible 70-kDa heat
      shock protein (HSP-70i) in many rodent organs. We used human intestinal
      epithelial T84 cells to characterize the inhibitory effect of L-NNA on HS-induced
      HSP-70i expression. Intracellular Ca(2+) concentration ([Ca(2+)](i)) was measured
      using fura-2, and protein kinase C (PKC), and PKA activities were determined. HS
      increased HSP-70i mRNA and protein in T84 cells exposed to 45 degrees C for 10
      min and allowed to recover for 6 h. L-NNA treatment for 1 h before HS inhibited
      the induction of HSP-70i mRNA and protein, with an IC(50) of 0.0471 +/- 0.0007
      microM. Because the HS-induced increase in HSP-70i mRNA and protein is Ca(2+)
      dependent, we measured [Ca(2+)](i) after treating cells with L-NNA. L-NNA at 100
      microM significantly decreased resting [Ca(2+)](i). Likewise, treatment with 1
      microM GF-109203X or H-89 (inhibitors of PKC and PKA, respectively) for 30 min
      also significantly decreased [Ca(2+)](i) and inhibited HS-induced increase in HSP
      70i. GF-109203X- or H-89-treated cells failed to respond to L-NNA by further
      decreasing [Ca(2+)](i) and HSP-70i. L-NNA effectively blocked heat shock factor-1
      (HSF1) translocation from the cytosol to the nucleus, a process requiring PKC
      phosphorylation. These results suggest that L-NNA inhibits HSP-70i by reducing
      [Ca(2+)](i) and decreasing PKC and PKA activity, thereby blocking HSF1
      translocation from the cytosol to the nucleus.

PMID- 11841992
TI  - Effect of GLP-1 on gastric volume, emptying, maximum volume ingested, and
      postprandial symptoms in humans.
AB  - Glucagon-like peptide-1 (GLP-1) relaxes the stomach during fasting but decreases
      hunger and food consumption and retards gastric emptying. The interrelationships
      between volume, emptying, and postprandial symptoms in response to GLP-1 are
      unclear. We performed, in healthy human volunteers, a placebo-controlled study of
      the effects of intravenous GLP-1 on gastric volume using (99m)Tc-single photon
      emission computed tomography imaging, gastric emptying of a nutrient liquid meal
      (Ensure) using scintigraphy, maximum tolerated volume (MTV) of Ensure, and
      postprandial symptoms 30 min after MTV. The role of vagal cholinergic function in
      the effects of GLP-1 was assessed by human pancreatic polypeptide (HPP) response
      to the Ensure meal. GLP-1 increased fasting and postprandial gastric volumes and
      retarded gastric emptying; MTV and postprandial symptoms were not different
      compared with controls. Effects on postprandial gastric function were associated
      with reduced postprandial HPP levels. GLP-1 does not induce postprandial symptoms
      despite significant inhibition of gastric emptying and vagal function; this may
      be partly explained by the increase in postprandial gastric volume.

PMID- 11841993
TI  - Role of epidermal growth factor and its receptor in chemotherapy-induced
      intestinal injury.
AB  - Several growth factors are trophic for the gastrointestinal tract and able to
      reduce the degree of intestinal damage caused by cytotoxic agents. However,
      studies of epidermal growth factor (EGF) for chemotherapy-induced intestinal
      injury are conflicting. The development of a transgenic mouse that specifically
      overexpresses EGF in the small intestine provided a unique opportunity to assess
      the contribution of EGF in mucositis. After a course of fluorouracil, transgenic
      mice fared no better than control mice. Weight recovery was inferior, and mucosal
      architecture was not preserved. Apoptosis was not decreased and proliferation was
      not increased in the crypts. To corroborate the findings in transgenic mice, ICR
      mice were treated with exogenous EGF after receiving fluorouracil. Despite ileal
      upregulation of native and activated EGF receptor, the mice were not protected
      from intestinal damage. No benefits were observed with different EGF doses or
      schedules or routes of EGF administration. Finally, mucositis was induced in
      mutant mice with specific defects of the EGF signaling axis. Compared with
      control mice, clinical and histological parameters of intestinal injury after
      fluorouracil were no different in waved-2 mice, which have functionally
      diminished EGF receptors, or waved-1 mice, which lack transforming growth factor
      alpha, another major ligand for the EGF receptor. These findings do not support a
      critical role for EGF or its receptor in chemotherapy-induced intestinal injury.

PMID- 11841994
TI  - The proximal colonic motor response to rectal mechanical and chemical
      stimulation.
AB  - We aimed to determine whether rectal distension and/or infusion of bile acids
      stimulates propagating or nonpropagating activity in the unprepared proximal
      colon in 10 healthy volunteers using a nasocolonic manometric catheter (16
      recording sites at 7.5-cm spacing). Sensory thresholds and proximal colonic motor
      responses were assessed following rectal distension by balloon inflation and
      rectal instillation of chenodeoxycholic acid. Maximum tolerated balloon volume
      and the volume that stimulated a desire to defecate were both significantly (P <
      0.01) reduced after rectal chenodeoxycholic acid. The frequency of colonic
      propagating pressure wave sequences decreased significantly in response to
      initial balloon inflations (P < 0.05), but the frequency doubled after subsequent
      chenodeoxycholic acid infusion (P < 0.002). Nonpropagating activity decreased
      after balloon inflation, was not influenced by acid infusion, and demonstrated a
      further decrease in response to repeat balloon inflation. We concluded that
      rectal chenodeoxycholic acid in physiological concentrations is a potent stimulus
      for propagating pressure waves arising in the proximal colon and reduces rectal
      sensory thresholds. Rectal distension inhibits all colonic motor activity.

PMID- 11841995
TI  - Caspase 8-mediated cleavage of plectin precedes F-actin breakdown in acinar cells
      during pancreatitis.
AB  - Pancreatic acinar cells depend on the integrity of the cytoskeleton for regulated
      secretion. Stimulation of isolated rat pancreatic acini with the secretagogue CCK
      serves as a model for human acute edematous pancreatitis. It induces the
      breakdown of the actin filament system (F-actin) with the consecutive inhibition
      of secretion and premature activation of digestive enzymes. However, the
      mechanisms that regulate F-actin breakdown are largely unknown. Plectin is a
      versatile cytolinker protein regulating F-actin dynamics in fibroblasts. It was
      recently demonstrated that plectin is a substrate of caspase 8. In pancreatic
      acinar cells, plectin strongly colocalizes with apical and basolateral F-actin.
      Supramaximal secretory stimulation of acini with CCK leads to a rapid
      redistribution and activation of caspase 8, followed by degradation of plectin
      that in turn precedes the F-actin breakdown. Inhibition of caspase 8 before CCK
      hyperstimulation prevents plectin cleavage, stabilizes F-actin morphology, and
      reverses the inhibition of secretion. Thus we propose that the caspase 8-mediated
      degradation of plectin represents a critical biochemical event during CCK-induced
      secretory blockade and cell injury.

PMID- 11841997
TI  - Localization and effects of orexin on fasting motility in the rat duodenum.
AB  - The orexins [orexin A (OXA) and orexin B (OXB)] are novel neuropeptides that
      increase food intake in rodents. The aim of this study was to determine the
      distribution of orexin and orexin receptors (OX1R and OX2R) in the rat duodenum
      and examine the effects of intravenous orexin on fasting gut motility. OXA-like
      immunoreactivity was found in varicose nerve fibers in myenteric and submucosal
      ganglia, the circular muscle, the mucosa, submucosal and myenteric neurons, and
      numerous endocrine cells of the mucosa. OXA neurons displayed choline
      acetyltransferase immunoreactivity, and a subset contained vasoactive intestinal
      peptide. OXA-containing endocrine cells were identified as enterochromaffin (EC)
      cells based on the presence of 5-hydroxytryptamine immunoreactivity. OX1R was
      expressed by neural elements of the gut, and EC cells expressed OX2R. OXA at 100
      and 500 pmol x kg(-1) x min(-1) significantly increased the myoelectric motor
      complex (MMC) cycle length compared with saline. Similarly, OXB increased the MMC
      cycle length at 100 pmol x kg(-1) x min(-1), but there was no further effect at
      500 pmol x kg(-1) x min(-1). We postulate that orexins may affect the MMC through
      actions on enteric neurotransmission after being released from EC cells and/or
      enteric neurons.

PMID- 11841996
TI  - Animal model for angiotensin II effects in the internal anal sphincter smooth
      muscle: mechanism of action.
AB  - Effect of ANG II was investigated in in vitro smooth muscle strips and in
      isolated smooth muscle cells (SMC). Among different species, rat internal and
      sphincter (IAS) smooth muscle showed significant and reproducible contraction
      that remained unmodified by different neurohumoral inhibitors. The AT(1)
      antagonist losartan but not AT(2) antagonist PD-123319 antagonized ANG II-induced
      contraction of the IAS smooth muscle and SMC. ANG II-induced contraction of rat
      IAS smooth muscle and SMC was attenuated by tyrosine kinase inhibitors genistein
      and tyrphostin, protein kinase C (PKC) inhibitor H-7, Ca(2+) channel blocker
      nicardipine, Rho kinase inhibitor Y-27632 or p(44/42) mitogen-activating protein
      kinase (MAPK(44/42)) inhibitor PD-98059. Combinations of nicardipine and H-7, Y
      27632, and PD-98059 caused further attenuation of the ANG II effects. Western
      blot analyses revealed the presence of both AT(1) and AT(2) receptors. We
      conclude that ANG II causes contraction of rat IAS smooth muscle by the
      activation of AT(1) receptors at the SMC and involves multiple intracellular
      pathways, influx of Ca(2+), and activation of PKC, Rho kinase, and MAPK(44/42).

PMID- 11841998
TI  - Region-specific ontogeny of alpha-2,6-sialyltransferase during normal and
      cortisone-induced maturation in mouse intestine.
AB  - Regional differences in the ontogeny of mouse intestinal alpha-2,6
      sialyltransferase activities (alpha-2,6-ST) and the influence of cortisone
      acetate (CA) on this expression were determined. High ST activity and alpha-2,6
      ST mRNA levels were detected in immature small and large intestine, with activity
      increasing distally from the duodenum. As the mice matured, ST activity
      (predominantly alpha-2,6-ST) in the small intestine decreased rapidly to adult
      levels by the fourth postnatal week. CA precociously accelerated this region
      specific ontogenic decline. A similar decline of ST mRNA levels reflected ST
      activity in the small, but not the large, intestine. Small intestinal sialyl
      alpha-2,6-linked glycoconjugates displayed similar developmental and CA induced
      precocious declines when probed using Sambucus nigra agglutinin (SNA) lectin. SNA
      labeling demonstrated age-dependent diminished sialyl alpha2,6 glycoconjugate
      expression in goblet cells in the small (but not large) intestine, but no such
      regional specificity was apparent in microvillus membrane. This suggests
      differential regulation of sialyl alpha-2,6 glycoconjugates in absorptive vs.
      globlet cells. These age-dependent and region-specific differences in sialyl
      alpha-2,6 glycoconjugates may be mediated in part by altered alpha-2,6-ST gene
      expression regulated by trophic factors such as glucocorticoids.

PMID- 11841999
TI  - Molecular cloning and functional analysis of the human Na(+)/H(+) exchanger NHE3
      promoter.
AB  - Na(+)/H(+) exchanger (NHE) isoforms NHE2 and NHE3, colocalized to the brush
      border membrane of the epithelial cells, exhibit differences in their pattern of
      tissue expression and regulation by various molecular signals. To investigate the
      mechanisms involved in regulation of NHE3 gene expression, the human NHE3
      promoter region was cloned and characterized. Primer extension experiments
      located the transcription start site to a position 116 nucleotides upstream from
      the translation start codon. The 5'-flanking region lacked a CCAAT box but
      contained a TATA-like sequence. Nucleotide sequencing of the 5'-flanking region
      revealed the presence of a number of cis elements including Sp1, AP-2, MZF-1,
      CdxA, Cdx-2, steroid and nonsteroid hormone receptor half sites, and a phorbol 12
      myristate 13-acetate-response element. Transient transfection experiments using
      C2/bbe cell line defined a maximal promoter activity in -95/+5 region. The
      regulatory response elements clustered within this region include a potential
      transcription factor IID (TF IID), a CACCC, two Sp1, and two AP-2 motifs.
      Deletion of a fragment containing the AP-2 and Sp1 motifs resulted in a drastic
      decrease in promoter activity. In gel mobility shift assays, an oligonucleotide
      spanning from -78 to -56 bp bound a recombinant AP-2, and the corresponding
      binding activity in nuclear extracts was supershifted with anti-AP2alpha
      antibody. Our studies suggest that the NHE3 expression is regulated by a
      combination of cis elements and their cognate transcription factors that include
      the AP-2 and Sp1 family members.

PMID- 11842001
TI  - Stimulation of chloride secretion by baicalein in isolated rat distal colon.
AB  - The effect of baicalein on mucosal ion transport in the rat distal colon was
      investigated in Ussing chambers. Mucosal addition of baicalein (1-100 microM)
      elicited a concentration-dependent short-circuit current (I(sc)) response. The
      increase in I(sc) was mainly due to Cl(-) secretion. The presence of mucosal
      indomethacin (10 microM) significantly reduced both the basal and subsequent
      baicalein-evoked I(sc) responses. The baicalein-induced I(sc) were inhibited by
      mucosal application of diphenylamine-2-carboxylic acid (100 microM) and
      glibenclamide (500 microM) and basolateral application of chromanol 293B (30
      microM), a blocker of K(v)LQT1 channels and Ba(2+) ions (5 mM). Treatment of the
      colonic mucosa with baicalein elicited a threefold increase in cAMP production.
      Pretreating the colonic mucosa with carbachol (100 microM, serosal) but not
      thapsigargin (1 microM, both sides) abolished the baicalein-induced I(sc).
      Addition of baicalein subsequent to forskolin induced a further increase in
      I(sc). These results indicate that the baicalein evoked Cl(-) secretion across
      rat colonic mucosa, possibly via a cAMP-dependent pathway. However, the action of
      baicalein cannot be solely explained by its cAMP-elevating effect. Baicalein may
      stimulate Cl(-) secretion via a cAMP-independent pathway or have a direct effect
      on cystic fibrosis transmembrane conductance regulator.

PMID- 11842002
TI  - Regulation of acid secretion and paracellular permeability by F-actin in the
      bullfrog, Rana catesbeiana.
AB  - Many studies have implicated F-actin in the regulation of gastric acid secretion
      using cytochalasin D (CD) to disrupt apical actin filaments in oxyntic cells.
      However, it is known that CD also affects mucosal permeability by disrupting
      tight junction structure. Here we investigated the contribution of F-actin to
      mucosal permeability and acid secretion in the stomach using CD. Stomachs were
      mounted in Ussing chambers and acid secretion (stimulated or inhibited),
      transepithelial resistance (TER), mannitol flux, bicarbonate transport, and dual
      mannitol/sodium fluxes were determined with or without CD. H(+) back diffusion
      was predicted from its diffusion coefficient. Incubation with CD resulted in a
      significant reduction in stimulated acid secretion. TER was unchanged in
      stimulated tissues but significantly reduced in inhibited tissues. Mannitol flux,
      bicarbonate transport, and H(+)-back diffusion increased significantly with CD.
      However, the rates of bicarbonate and H(+) flux were not large enough to account
      for the inhibition of acid secretion. These findings demonstrate that actin
      filaments regulate paracellular permeability and play an essential role in the
      regulation of acid secretion in the stomach.

PMID- 11842000
TI  - Alcohols enhance caerulein-induced zymogen activation in pancreatic acinar cells.
AB  - Activation of zymogens within the pancreatic acinar cell is an early feature of
      acute pancreatitis. Supraphysiological concentrations of cholecystokinin (CCK)
      cause zymogen activation and pancreatitis. The effects of the CCK analog,
      caerulein, and alcohol on trypsin and chymotrypsin activation in isolated
      pancreatic acini were examined. Caerulein increased markers of zymogen activation
      in a time- and concentration-dependent manner. Notably, trypsin activity reached
      a peak value within 30 min, then diminished with time, whereas chymotrypsin
      activity increased with time. Ethanol (35 mM) sensitized the acinar cells to the
      effects of caerulein (10(-10) to 10(-7) M) on zymogen activation but had no
      effect alone. The effects of ethanol were concentration dependent. Alcohols with
      a chain length of >or=2 also sensitized the acinar cell to caerulein; the most
      potent was butanol. Branched alcohols (2-propanol and 2-butanol) were less potent
      than aliphatic alcohols (1-propanol and 1-butanol). The structure of an alcohol
      is related to its ability to sensitize acinar cells to the effects of caerulein
      on zymogen activation.

PMID- 11842004
TI  - The ferrireductase paraferritin contains divalent metal transporter as well as
      mobilferrin.
AB  - Inorganic iron can be transported into cells in the absence of transferrin.
      Ferric iron enters cells utilizing an integrin-mobilferrin-paraferritin pathway,
      whereas ferrous iron uptake is facilitated by divalent metal transporter-1 (DMT
      1). Immunoprecipitation studies using antimobilferrin antibody precipitated the
      previously described large-molecular-weight protein complex named paraferritin.
      It was previously shown that paraferritin functions as an intracellular
      ferrireductase, reducing ferric iron to ferrous iron utilizing NADPH as the
      energy source. It functions in the pathway for the cellular uptake of ferric
      iron. This multipeptide protein contains a number of active peptides, including
      the ferric iron binding protein mobilferrin and a flavin monooxygenase. The
      immunoprecipitates and purified preparations of paraferritin also contained DMT
      1. This identifies DMT-1 as one of the peptides constituting the paraferritin
      complex. Since paraferritin functions to reduce newly transported ferric iron to
      ferrous iron and DMT-1 can transport ferrous iron, these findings suggest a role
      for DMT-1 in conveyance of iron from paraferritin to ferrochelatase, the enzyme
      utilizing ferrous iron for the synthesis of heme in the mitochondrion.

PMID- 11842003
TI  - Copper repletion enhances apical iron uptake and transepithelial iron transport
      by Caco-2 cells.
AB  - The influence of copper status on Caco-2 cell apical iron uptake and
      transepithelial transport was examined. Cells grown for 7-8 days in media
      supplemented with 1 microM CuCl(2) had 10-fold higher cellular levels of copper
      compared with control. Copper supplementation did not affect the integrity of
      differentiated Caco-2 cell monolayers grown on microporous membranes. Copper
      repleted cells displayed increased uptake of iron as well as increased transport
      of iron across the cell monolayer. Northern blot analysis revealed that
      expression of the apical iron transporter divalent metal transporter-1 (DMT1),
      the basolateral transporter ferroportin-1 (Fpn1), and the putative ferroxidase
      hephaestin (Heph) was upregulated by copper supplementation, whereas the recently
      identified ferrireductase duodenal cytochrome b (Dcytb) was not. These results
      suggest that DMT1, Fpn1, and Heph are involved in the iron uptake process
      modulated by copper status. Although a clear role for Dcytb was not identified,
      an apical surface ferrireductase was modulated by copper status, suggesting that
      its function also contributes to the enhanced iron uptake by copper-repleted
      cells. A model is proposed wherein copper promotes iron depletion of intestinal
      Caco-2 cells, creating a deficiency state that induces upregulation of iron
      transport factors.

PMID- 11842006
TI  - Role of TGF-beta1 in the development of pancreatic fibrosis in Otsuka Long-Evans
      Tokushima Fatty rats.
AB  - Recently established Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of
      naturally occurring obesity diabetes, exhibit progressive accumulation of
      connective tissue in the pancreas. The present study was designed to determine
      the pathogenic role of transforming growth factor-beta1 (TGF-beta1) in the
      development of pancreatic fibrosis in OLETF rats by investigating the serial
      changes in the expression of TGF-beta1 and extracellular matrix (ECM) in the
      pancreas. Progressive proliferation of connective tissue arose from the
      interstitial region surrounding islets at 20 wk of age and extended to the
      exocrine pancreas adjacent to the islets. TGF-beta1 mRNA levels in the pancreas
      increased at 20 wk of age and reached a peak value at 30 wk of age. Fibronectin
      (FN) and procollagen types I and III mRNAs peaked at 20 wk of age and remained at
      higher levels than those in the nondiabetic counterparts Long-Evans Tokushima
      Otsuka rats until 50 wk of age. Immunoreactivities for TGF-beta1 and FN were
      found in islets of OLETF rats at 20 wk of age and were seen in acinar and
      interstitial cells at 50 wk of age. Moreover, alpha-smooth muscle actin was
      located at interstitial region surrounding the islets. Proliferation of the
      connective tissue in the pancreas of OLETF rats closely correlated with
      expression of TGF-beta1 and ECM. Our results suggest that the development of
      pancreatic fibrosis in OLETF rats extends from endocrine to exocrine pancreas and
      that TGF-beta1 is involved in pancreatic fibrosis of OLETF rats.

PMID- 11842005
TI  - Asynchronous expression and colocalization of Bsep and Mrp2 during development of
      rat liver.
AB  - In the liver, function of the bile salt export pump (Bsep), a major canalicular
      exporter of bile salts, is complemented by activity of the multidrug resistance
      protein 2 (Mrp2), a canalicular organic anions transporter. Mrp2 was found
      capable of transporting various anticancer drugs out of cells, eventually
      undermining their therapeutic potential and contributing to multidrug resistance.
      We employed a RT-PCR, immunoblotting, and immunofluorescence to examine their
      gene, protein expression, and distribution of antigenic sites in the rat liver
      during development from 16-day-old fetus to adult animal. Bsep mRNA was almost
      undetectable before birth. It was first clearly expressed in the liver of newborn
      rats. On the contrary, Mrp2 mRNA was seen before birth, although at low levels.
      In concert with mRNA expression, Bsep protein was undetectable before birth,
      while Mrp2 protein was already expressed. Both proteins were clearly detectable
      in the postnatal period. Confocal immunofluorescent microscopy showed
      asynchronous appearance of Bsep and Mrp2 proteins during development but their
      colocalization in the bile canaliculi once each one is expressed. During the
      gestational period, a weak immunofluorescence for Mrp2 was observed only in
      livers of 16-day-old embryos. No fluorescence for Bsep was seen. Both proteins
      were clearly visualizable after birth, although the pattern of immunostaining
      varied. These findings provide molecular evidence that expression of both Bsep
      and Mrp2 during development is transcriptionally regulated. They also point out
      the differences in relevance to the liver function of the systems responsible for
      canalicular transport of bile salts versus organic anions.

PMID- 11842007
TI  - Ontogenetic expression and regulation of Na(+)-D-glucose cotransporter in jejunum
      of domestic chicken.
AB  - To evaluate the effect of age on sugar transport, we determined the uptake of
      methyl alpha-D-glucopyranoside and the abundance of the Na(+)-D-glucose
      cotransporter (SGLT1) in jejunal brush-border membrane (BBM) vesicles of 2-day-
      and 5-wk-old chickens. Methyl alpha-D-glucopyranoside transport per BBM protein
      was 40% lower in adults than in newly hatched chickens. This finding was matched
      by parallel declines in site density of SGLT1, which were detected by Western
      blot. The immunohistochemical study showed that SGLT1 was exclusively located in
      the BBM of enterocytes along the entire villus and was absent in the crypt in
      both age groups, and there was an 11-fold increase in the total absorptive area
      during development. Northern blot studies of the abundance of SGLT1 mRNA showed
      similar levels for the groups studied. We conclude that the age-related decline
      in Na(+)-dependent hexose transport per unit of BBM protein in the chicken
      jejunum is due to a reduction in the density of SGLT1 cotransporter and is
      regulated by a posttranscriptional mechanism.

PMID- 11842008
TI  - Adenovirus-mediated gene transfer to nonparenchymal cells in normal and injured
      liver.
AB  - Adenovirus-mediated gene transfer has become an important tool with which to
      introduce genetic material into cells. Available data emphasize efficient
      adenoviral transduction of parenchymal liver cells (i.e., hepatocytes) in both in
      vitro and in vivo model systems, typically in normal cells. The aim of this study
      was to evaluate gene transfer to nonparenchymal (and parenchymal) cells of the
      normal and injured rat liver. Hepatocytes, stellate cells, and endothelial cells
      were isolated by standard methods. Liver injury was induced by bile duct ligation
      or carbon tetrachloride administration. Cells were transduced in vitro with an
      adenovirus encoding beta-galactosidase (Ad.beta-gal) over a range of viral
      titers, and transduced cells were identified by detection of X-gal. In vivo
      transduction efficiency was studied in normal and injured livers using cell
      isolation techniques. Nonparenchymal cells were transduced with greater frequency
      than hepatocytes at all adenoviral titers tested, both in vitro and in vivo.
      After liver injury, adenoviral transduction was reduced for all liver cell types
      compared with that for cells from normal livers (at all virus titers). Notably,
      transduction efficiency remained greater in nonparenchymal cells than in
      hepatocytes after liver injury. This work implies that, to achieve comparable
      gene expression in the injured liver, higher adenoviral titers may be required,
      an important consideration as gene therapy in disease states is considered.

PMID- 11842009
TI  - Identification of an apical Cl(-)/HCO3(-) exchanger in the small intestine.
AB  - HCO3(-) secretion is the most important defense mechanism against acid injury in
      the duodenum. However, the identity of the transporter(s) mediating apical HCO3(
      ) secretion in the duodenum remains unknown. A family of anion exchangers, which
      include downregulated in adenoma (DRA or SLC26A3), pendrin (PDS or SLC26A4), and
      the putative anion transporter (PAT1 or SLC26A6) has recently been identified.
      DRA and pendrin mediate Cl(-)/base exchange; however, the functional identity and
      distribution of PAT1 (SLC26A6) is not known. In these studies, we investigated
      the functional identity, tissue distribution, and membrane localization of PAT1.
      Expression studies in Xenopus oocytes demonstrated that PAT1 functions in Cl(
      )/HCO3(-) exchange mode. Tissue distribution studies indicated that the
      expression of PAT1 is highly abundant in the small intestine but is low in the
      colon, a pattern opposite that of DRA. PAT1 was also abundantly detected in
      stomach and heart. Immunoblot analysis studies identified PAT1 as a approximately
      90 kDa protein in the duodenum. Immunohistochemical studies localized PAT1 to the
      brush border membranes of the villus cells of the duodenum. We propose that PAT1
      is an apical Cl(-)/HCO3(-) exchanger in the small intestine.

PMID- 11842010
TI  - How to tell a sea monster: molecular discrimination of large marine animals of
      the North Atlantic.
AB  - Remains of large marine animals that wash onshore can be difficult to identify
      due to decomposition and loss of external body parts, and in consequence may be
      dubbed "sea monsters." DNA that survives in such carcasses can provide a basis of
      identification. One such creature washed ashore at St. Bernard's, Fortune Bay,
      Newfoundland, in August 2001. DNA was extracted from the carcass and
      enzymatically amplified by the polymerase chain reaction (PCR): the mitochondrial
      NADH2 DNA sequence was identified as that of a sperm whale (Physeter catodon).
      Amplification and sequencing of cryptozoological DNA with "universal" PCR primers
      with broad specificity to vertebrate taxa and comparison with species in the
      GenBank taxonomic database is an effective means of discriminating otherwise
      unidentifiable large marine creatures.

PMID- 11842011
TI  - Apical sensory organ in larvae of the patellogastropod Tectura scutum.
AB  - The apical sensory organ in veliger larvae of a patellogastropod, a basal clade
      of gastropod molluscs, was studied using ultrastructural and immunohistochemical
      techniques. Immediately before veligers of Tectura scutum undergo ontogenetic
      torsion, the apical sensory organ consists of three large cells that generate a
      very long apical ciliary tuft, two cells that generate a bilateral pair of
      shorter ciliary tufts, and a neural ganglion (apical ganglion). Putative sensory
      neurons forming the ganglion give rise to dendrites that extend to the apical
      surface of the larva and to basal neurites that contribute to a neuropil. The
      ganglion includes only one ampullary neuron, a distinctive neuronal type found in
      the apical ganglion of other gastropod veligers. Serotonin immunoreactivity is
      expressed by a medial and two lateral neurons, all having an apical dendrite, and
      also by neurites within the neuropil and by peripheral neurites that run beneath
      the ciliated prototrochal cells that power larval swimming. The three cells
      generating the long apical ciliary tuft are lost soon after ontogenetic torsion,
      and the medial serotonergic cell stops expressing serotonin antigenicity in late
      stage veligers. The lateral ciliary tuft cells of T. scutum may be homologs of
      lateral ciliary tuft cells in planktotrophic opisthobranch veligers. A tripartite
      arrangement of sensory dendrites, as described previously for veligers of other
      gastropod clades, can be recognized in T. scutum after loss of the apical ciliary
      tuft cells.

PMID- 11842012
TI  - Localization and quantification of gonad serotonin during gametogenesis of the
      surf clam, Spisula solidissima.
AB  - In the surf clam, Spisula solidissima, serotonin was reported to induce spawning
      when injected into the gonads. At nanomolar concentrations, it facilitates the
      fertilizability of oocyte by sperm, at micromolar concentration, it triggers the
      meiotic maturation of prophase 1-arrested oocytes, thus mimicking the effect of
      sperm. To further understand the role of serotonin in the gametogenic and
      spawning processes, we used both immunohistochemistry and high-pressure liquid
      chromatography linked with electrochemical detection to detect serotonin in the
      gonads of the surf clam. We found serotonin-containing varicose fibers covering
      the surface of the germinal epithelium in both sexes. The area occupied by the
      serotonergic innervation field encircling gonad acini varied according to the
      gonadal stages (active phase, ripe phase, partially spawned phase, spent phase).
      We also found large variations in the serotonin concentration between specimens
      during the gametogenic cycle. The serotonin concentration was correlated with
      gonad growth: it decreased in the ripe phase in comparison with the previous
      phase, the active phase. We attribute the decrease to the increase of total gonad
      mass in this stage. In contrast, as spawning begins, the total gonad mass
      declines while the gonad serotonin concentration increases to a level similar to
      that found in active phase. The finding that prior to spawning, serotonin is
      present in the gonads within fibers exhibiting distinct varicosities suggests
      that it is implicated in spawning.

PMID- 11842013
TI  - Fertilization success in marine invertebrates: the influence of gamete age.
AB  - Gamete age has been postulated to be unimportant to the fertilization ecology of
      marine invertebrates. However, recent research suggests that, for some species at
      least, it may have a direct impact upon fertilization success. We present
      comparative data on the influence of gamete age on fertilization and development
      success in several marine invertebrates: the polychaetes Arenicola marina and
      Nereis virens and the asteroid echinoderm Asterias rubens. Oocytes are much
      longer lived in the polychaetes than in the echinoderm, with A. marina oocytes
      still capable of fertilizing and developing normally 96 h post-spawning.
      Developmental abnormalities and failure to reach blastula tend to occur well
      before the fertilizable life of the oocytes has expired. Sperm are similarly
      longer lived in the polychaetes; however, fertilizing capacity is markedly
      reduced following incubation in conspecific egg-conditioned seawater. These
      results are discussed in terms of the fertilization strategies of the three
      species. We further suggest that, for A. marina at least, longer-lived sperm and
      eggs are central to the fertilization strategy of this species.

PMID- 11842014
TI  - Morphological variations among larval-postlarval intermediates produced by
      eyestalk ablation in the snapping shrimp Alpheus heterochaelis Say.
AB  - The eyestalk of many crustaceans contains the X-organ, the presumptive site of
      production and release of many protein and peptide hormones into the hemolymph.
      Removal of the eyestalk deprives the animal of these hormones and is known to
      affect many physiological processes in the adult and developing larva. In the
      snapping shrimp Alpheus heterochaelis Say, eyestalk ablation performed early in
      larval development has profound effects on morphogenesis, causing the appearance
      of supernumerary larval stages, accompanied by retardation and even complete
      arrest of morphogenesis. In this study, we examined the effects on morphogenesis
      of bilateral eyestalk removal at carefully controlled intervals. We found that
      the crucial point for this operation-the point at which the animal attains the
      ability to metamorphose fully-is just before the onset of ecdysis to the third
      instar. Additionally, the pattern of development and morphogenesis among body
      segments follows a discernible double gradient pattern along the anterior
      posterior axis in which the extremities of the animal attain the potential for
      morphogenetic advance prior to the central thorax. This pattern of morphogenesis,
      punctuated by ecdysis, is a continuous rather than a stepwise or
      compartmentalized phenomenon.

PMID- 11842015
TI  - Uptake of the neurotransmitter histamine into the eyes of larvae of the barnacle
      (Balanus amphitrite).
AB  - The photoreceptors of adult barnacles use histamine as their neurotransmitter and
      take up (3)H-histamine selectively from the extracellular medium. We assayed for
      the uptake of (3)H-histamine into the eyes of the free-swimming (nauplius) and
      settling (cyprid) larval stages of Balanus amphitrite. The extracellular space of
      nauplii proved permeable to dyes below about 800 molecular weight (MW),
      indicating that (3)H-histamine (MW 111) introduced into seawater would have
      access to internal structures. (3)H-Histamine was taken up into nauplii by a
      process with a K(D) of 0.32 microM. Uptake was antagonized by chlorpromazine,
      which also blocks uptake of (3)H-histamine into adult photoreceptors. In
      autoradiographs of serial sections of nauplii and cyprids incubated in (3)H
      histamine, the ocelli and compound eyes were labeled; other structures in the
      animal were not. No eyes or other structures were labeled with (3)H-serotonin, a
      related amine whose transporter commonly transports histamine as well. These
      experiments show that a histamine-specific transporter similar to that found in
      the adult is expressed in all of the eyes of barnacle larvae. In the ocelli,
      where photoreceptors and pigment cells may be distinguished in the light
      microscope, label was unexpectedly concentrated far more over the pigment cells
      than over the photoreceptors.

PMID- 11842016
TI  - Glycoproteins from the cuticle of the Atlantic shore crab Carcinus maenas: I.
      Electrophoresis and Western-blot analysis by use of lectins.
AB  - The protein and glycoprotein content of four different neutral or acidic solvent
      extracts (0.5 M KCl, 10% EDTA, 0.1 N HCl, or 2% acetic acid) from the mineralized
      exoskeleton of a decapod crustacean, the Atlantic shore crab Carcinus maenas,
      were characterized by quantitative analysis of proteins, SDS-PAGE analysis, and
      probing with lectins on blots. The lectins used were Conconavalin A, Jacalin,
      soybean agglutinin, Maackia amurensis agglutinin II, and Sambucus nigra
      agglutinin. The results show that many proteins can be obtained from the crab
      cuticle without strong denaturants in the extraction medium. Many of the
      extracted cuticle proteins appeared to be glycosylated, bearing O-linked
      oligosaccharides and N-linked mannose-rich glycans. N-acetyl-galactosamine and N
      acetylneuraminic acids were revealed, for the first time, as terminal residues on
      N-linked mannose-rich structures of crab cuticle glycoproteins. Sialylated
      glycoproteins might thus be involved in organic-mineral interactions in the
      calcified crab exoskeleton. The amount and variety of glycoproteins extracted
      with the acidic solvents are obviously different from those extracted with
      neutral solvents. HCl proved to be the best of the tested extraction solvents and
      a valuable alternative to EDTA.

PMID- 11842017
TI  - Specificity of a model cnidarian-dinoflagellate symbiosis.
AB  - To understand the flexibility of symbiotic associations in coral reefs, we
      investigated the specificity of the Aiptasia (cf. insignis)-Symbiodinium
      association in the laboratory by rendering the anemones aposymbiotic and
      inoculating them with different isolates of SYMBIODINIUM: Infective algal
      symbionts were monitored over 3 months by re-isolation and identification using
      denaturing-gradient gel electrophoresis and sequence comparison of their
      amplified 18S rRNA hypervariable V1 + V2 gene region. Despite similarity in their
      external morphology, the algal isolates differed in their infectivity towards the
      host. Within days of single-isolate inoculation, aposymbiotic anemones formed
      associations with fresh or cultured isolates (clade B) from the anemones Aiptasia
      sp. or A. tagetes, respectively. They associated to a limited extent with
      cultured isolates (clade A) from the tridacnids Tridacna crocea or Hippopus
      hippopus, and not at all with a cultured isolate (clade C) from the stony coral
      Montipora verrucosa, nor with a free-living isolate (clade A) from subtidal
      sands. Aposymbiotic anemones inoculated with a mixture of all isolates had only
      the anemone taxon as their detectable symbionts. Re-inoculation of induced
      symbioses with a mixture of all isolates and incubation with wild anemones showed
      that the initial induced symbioses with the anemone taxon were stable. Anemones
      originally infected with tridacnid isolates either additionally acquired the
      anemone taxon or had the former outgrown by the latter. These results demonstrate
      the presence of a host-symbiont recognition mechanism, and possibly competition
      among potential algal symbionts in the Aiptasia-Symbiodinium association. Here we
      present a method that may be useful in monitoring the algal population dynamics
      in symbiotic corals in the field, along with an efficient method of rendering
      Aiptasia aposymbiotic for further laboratory investigation of Aiptasia
      Symbiodinium symbioses.

PMID- 11842018
TI  - Morphological plasticity in the tropical sponge Anthosigmella varians: responses
      to predators and wave energy.
AB  - The goal of the research presented here was to examine phenotypic plasticity
      exhibited by three morphotypes of the common Caribbean sponge Anthosigmella
      varians (Duchassaing & Michelotti). We were interested in examining the biotic
      (and, to a lesser extent, abiotic) factors responsible for branch production in
      this species. We also tested the hypothesis that the skeleton may serve an
      antipredator function in this sponge, focusing on vertebrate fish predators
      (i.e., angelfish) in this work. In transplant and caging experiments, unprotected
      forma varians replicates were immediately consumed by angelfish, while caged
      replicates persisted on the reef for several months. These findings support the
      hypothesis that predators (and not wave energy) restrict forma varians to
      lagoonal habitats. Branch production was not observed in A. varians forma
      incrustans when sponges were protected from predators or placed in predator-free,
      low-wave-energy environments. It is not clear from our work whether forma
      incrustans is capable of producing branches (i.e., whether branch production is a
      plastic trait in this morph). Additional field experiments demonstrated that A.
      varians forma varians increased spicule concentrations, compared to uninjured
      sponges, in response to artificial predation events, and A. varians forma rigida
      reduced spicule concentrations, compared to uncaged controls, when protected from
      predators. These findings indicate that spicule concentration is a plastic
      morphological trait that can be induced by damage, and that A. varians may be
      able to reduce spicule concentrations when environmental conditions change (e.g.,
      in the absence of predators). The potential significance of inducible defenses
      and structural anti-predator defenses in sponges is discussed in relation to
      recent work on sponge chemical defenses.

PMID- 11842019
TI  - Effects of carotid and aortic chemoreceptor denervation in newborn piglets.
AB  - The objective of the present study was to test the hypothesis that in neonatal
      piglets there would be no hypoventilation after sham denervation or aortic
      denervation (AOD) alone, but there would be transient hypoventilation after
      carotid body denervation (CBD) and the hypoventilation would be greatest after
      combined carotid and aortic denervation (CBD+AOD). There was a significant (P <
      0.05) hypoventilation in CBD and CBD+AOD piglets denervated at 5, 15, and 25 days
      of age. The hypoventilation in CBD+AOD piglets denervated at 5 days of age was
      greater (P < 0.05) than that of all other groups. Conversely, sham-denervated and
      AOD piglets did not hypoventilate after denervation. Injections of sodium cyanide
      showed that aortic chemoreceptors were a site of recovery of peripheral
      chemosensitivity after CBD. This aortic sodium cyanide response was abolished by
      prior injection of a serotonin 5a receptor blocker. Residual peripheral
      chemosensitivity after CBD+AOD was localized to the left ventricle. We conclude
      that 1) aortic chemoreceptors contribute to eupneic breathing in piglets that
      were carotid denervated at 5 days of age and 2) there are multiple sites of
      residual peripheral chemosensitivity after CBD.

PMID- 11842020
TI  - Mechanisms of flow and ACh-induced dilation in rat soleus arterioles are altered
      by hindlimb unweighting.
AB  - The purpose of this study was to test the hypothesis that endothelium-dependent
      dilation (flow-induced dilation and ACh-induced dilation) in rat soleus muscle
      arterioles is impaired by hindlimb unweighting (HLU). Male Sprague-Dawley rats
      (approximately 300 g) were exposed to HLU or weight-bearing control (Con)
      conditions for 14 days. Soleus first-order (1A) and second-order (2A) arterioles
      were isolated, cannulated, and exposed to step increases in luminal flow at
      constant pressure. Flow-induced dilation was not impaired by HLU in 1A or 2A
      arterioles. The cyclooxygenase inhibitor indomethacin (Indo; 50 microM) did not
      alter flow-induced dilation in 1As or 2As. Inhibition of nitric oxide synthase
      (NOS) with N(omega)-nitro-L-arginine (L-NNA; 300 microM) reduced flow-induced
      dilation by 65-70% in Con and HLU 1As. In contrast, L-NNA abolished flow-induced
      dilation in 2As from Con rats but had no effect in HLU 2As. Combined treatment
      with L-NNA + Indo reduced tone in 1As and 2As from Con rats, but flow-induced
      dilation in the presence of L-NNA + Indo was not different from responses without
      inhibitors in either Con or HLU 1As or 2As. HLU also did not impair ACh-induced
      dilation (10(-9)-10(-4) M) in soleus 2As. L-NNA reduced ACh-induced dilation by
      approximately 40% in Con 2As but abolished dilation in HLU 2As. Indo did not
      alter ACh-induced dilation in Con or HLU 2As, whereas combined treatment with L
      NNA + Indo abolished ACh-induced dilation in 2As from both groups. We conclude
      that flow-induced dilation (1As and 2As) was preserved after 2 wk HLU, but HLU
      decreased the contribution of NOS in mediating flow-induced dilation and
      increased the contribution of a NOS- and cyclooxygenase-independent mechanism
      (possibly endothelium-derived hyperpolarizing factor). In soleus 2As, ACh-induced
      dilation was preserved after 2-wk HLU but the contribution of NOS in mediating
      ACh-induced dilation was increased.

PMID- 11842021
TI  - Effects of fatigue and training on sarcoplasmic reticulum Ca(2+) regulation in
      human skeletal muscle.
AB  - Little is known about fatigue and training effects on sarcoplasmic reticulum (SR)
      function in human muscle, and we therefore investigated this in eight untrained
      controls (UT), eight endurance-trained (ET), and eight resistance-trained
      athletes (RT). Muscle biopsies (vastus lateralis) taken at rest and after 50
      maximal quadriceps contractions (180 degrees/s, 0.5 Hz) were analyzed for fiber
      composition, metabolites and maximal SR Ca(2+) release, Ca(2+) uptake, and Ca(2+)
      ATPase activity. Fatigue reduced (P < 0.05) Ca(2+) release (42.1 +/- 3.8%, 43.4
      +/- 3.9%, 31.3 +/- 6.1%), Ca(2+) uptake (43.0 +/- 5.2%, 34.1 +/- 4.6%, 28.4 +/-
      2.8%), and Ca(2+)-ATPase activity (38.6 +/- 4.2%, 48.5 +/- 5.7%, 29.6 +/- 5.0%),
      in UT, RT, and ET, respectively. These decreases were correlated with
      fatigability and with type II fiber proportion (P < 0.05). Resting SR measures
      were correlated with type II proportion (r > or = 0.51, P < 0.05). ET had lower
      resting Ca(2+) release, Ca(2+) uptake, and Ca(2+)-ATPase (P < 0.05) than UT and
      RT (P < 0.05), probably because of their lower type II proportion; only minor
      effects were found in RT. Thus SR function is markedly depressed with fatigue in
      controls and in athletes, is dependent on fiber type, and appears to be minimally
      affected by chronic training status.

PMID- 11842022
TI  - Postnatal expression of neurotransmitters, receptors, and cytochrome oxidase in
      the rat pre-Botzinger complex.
AB  - The pre-Botzinger complex (PBC) is postulated as the center of respiratory
      rhythmogenesis. Previously, we found a reduction or plateau of cytochrome oxidase
      (CO) activity in the PBC and other respiratory nuclei at postnatal days 3-4,
      despite a general increase of CO with age, suggesting a period of synaptic
      readjustment. The present study examined the expression of CO and a number of
      neurochemicals in the PBC at closer time intervals. At postnatal days 3-4 and,
      more prominently, at postnatal day 12, expression of CO, glutamate, and N-methyl
      D-aspartate receptor subunit 1 was reduced, whereas expression of GABA, GABA(B)
      receptor, glycine receptor, and alpha-amino-3-hydroxy-5-methylisoxazole-4
      propionic acid receptor subunit 2 was increased. These findings are consistent
      with our hypothesis that decreased CO activity is associated with an increase in
      inhibitory drive (mediated by GABA and glycine, their receptors, and possibly
      blockage of Ca(2+) entry by glutamate receptor subunit 2) and a decrease in
      excitatory drive (mediated by glutamate and its receptors). Our findings point to
      two critical periods during postnatal development of the rat when their
      respiratory system may be more vulnerable to respiratory insults.

PMID- 11842023
TI  - Gender modulates activation of renin-angiotensin and endothelin systems in
      hypertension and heart failure.
AB  - Sexual dimorphism may occur during the development of hypertension and congestive
      heart failure (CHF). Male and female spontaneous hypertension heart failure
      (SHHF) rats with established hypertension, but before CHF (age 5-8 mo) and during
      cardiac decompensation leading to CHF (age 18-20 mo in male rats and 22-24 mo in
      female rats), were studied. At 5-8 mo, male SHHF rats showed early activation of
      the renin-angiotensin system (RAS), as indicated by increased plasma renin
      activity (PRA) and higher serum angiotensin-converting enzyme activity compared
      with female rats. The increase in PRA in female rats was delayed compared with
      males rats, but it reached comparable levels just before CHF. Urinary endothelin
      excretion was significantly greater in 5- to 8-mo-old female rats compared with
      age-matched male rats. Urinary endothelin excretion increased in both male and
      female rats as CHF developed. Plasma atrial natriuretic peptide (ANP) was
      comparable at both time points, and both genders showed similar, marked increases
      as CHF developed. In conclusion, male rats show early activation of the RAS,
      whereas female rats show early activation of the endothelin vasopressor system.
      During cardiac decompensation, generalized activation of the RAS, endothelin, and
      ANP systems occurs and is similar in male and female SHHF rats.

PMID- 11842024
TI  - Alteration of contractile force and mass in the senescent diaphragm with beta(2)
      agonist treatment.
AB  - Aging is associated with a decrease in diaphragmatic maximal tetanic force
      production (P(o)) in senescent rats. Treatment with the beta(2)-agonist
      clenbuterol (CB) has been shown to increase skeletal muscle mass and P(o) in weak
      locomotor skeletal muscles from dystrophic rodents. It is unknown whether CB can
      increase diaphragmatic mass and P(o) in senescent rats. Therefore, we tested the
      hypothesis that CB treatment will increase specific P(o) (i.e., force per cross
      sectional area) and mass in the diaphragm of old rats. Young (5 mo) and old (23
      mo) male Fischer 344 rats were randomly assigned to one of the following groups
      (n = 10/group): 1) young CB treated; 2) young control; 3) old CB treated; and 4)
      old control. Animals were injected daily with either CB (2 mg/kg) or saline for
      28 days. CB increased (P < 0.05) the mass of the costal diaphragm in both young
      and old animals. CB treatment increased diaphragmatic-specific P(o) in old
      animals (approximately 15%; P < 0.05) but did not alter (P > 0.05) diaphragmatic
      specific P(o) in young animals. Biochemical analysis indicated that the improved
      maximal specific P(o) in the diaphragm of CB-treated old animals was not due to
      increased myofibrillar protein concentration. Analysis of the myosin heavy chain
      (MHC) content of the costal diaphragm revealed a CB-induced increase (P < 0.05)
      in type IIb MHC and a decrease in type I, IIa, and IIx MHC in both young and old
      animals. These data support the hypothesis that CB treatment can restore the age
      associated decline in both diaphragmatic-specific P(o) and muscle mass.

PMID- 11842025
TI  - Low-volume ventilation causes peripheral airway injury and increased airway
      resistance in normal rabbits.
AB  - Lung mechanics and morphometry of 10 normal open-chest rabbits (group A),
      mechanically ventilated (MV) with physiological tidal volumes (8-12 ml/kg), at
      zero end-expiratory pressure (ZEEP), for 3-4 h, were compared with those of five
      rabbits (group B) after 3-4 h of MV with a positive end-expiratory pressure
      (PEEP) of 2.3 cmH(2)O. Relative to initial MV on PEEP, MV on ZEEP caused a
      progressive increase in quasi-static elastance (+36%) and airway (Rint; +71%) and
      viscoelastic resistance (+29%), with no change in the viscoelastic time constant.
      After restoration of PEEP, quasi-static elastance and viscoelastic resistance
      returned to control levels, whereas Rint remained elevated (+22%). On PEEP, MV
      had no effect on lung mechanics. Gas exchange on PEEP was equally preserved in
      groups A and B, and the lung wet-to-dry ratios were normal. Both groups had
      normal alveolar morphology, whereas only group A had injured respiratory and
      membranous bronchioles. In conclusion, prolonged MV on ZEEP induces histological
      evidence of peripheral airway injury with a concurrent increase in Rint, which
      persists after restoration of normal end-expiratory volumes. This is probably due
      to cyclic opening and closing of peripheral airways on ZEEP.

PMID- 11842026
TI  - Measurement of hemodynamics in human carotid artery using ultrasound and
      computational fluid dynamics.
AB  - The objective of the study was to investigate the feasibility of using
      computational fluid dynamic modeling (CFD) with noninvasive ultrasound
      measurements to determine time-variant three-dimensional (3D) carotid arterial
      hemodynamics in humans in vivo. The effects of hyperoxia and hypoxic hypercapnia
      on carotid artery local hemodynamics were examined by use of this approach. Six
      normotensive volunteers followed a double-blind randomized crossover design.
      Blood pressure, heart rate, and carotid blood flow were measured while subjects
      breathed normal air, a mixture of 5% CO(2) and 15% O(2) (hypoxic hypercapnia),
      and 100% O(2) (hyperoxia). Carotid artery geometry was reconstructed on the basis
      of B-mode ultrasound images by using purpose-built image processing software.
      Time-variant 3D carotid hemodynamics were estimated by using finite volume-based
      CFD. Systemic blood pressure was not significantly affected by hyperoxia or
      hypoxic hypercapnia, but heart rate decreased significantly with hyperoxia. There
      was an increase in diastolic flow velocity in the external carotid artery after
      hypoxic hypercapnia, but otherwise carotid blood flow velocities did not change
      significantly. Compared with normal air, hyperoxic conditions were associated
      with a decrease in the width of the region of flow separation in the external
      carotid artery. During hyperoxia, there was also an increase in the minimum and a
      decrease in maximum shear stress in the bifurcation and hence a reduction in
      cyclic variation in shear stress. Hypoxic hypercapnia was associated with a
      reduced duration of flow separation in the external carotid artery and an
      increase in the minimum shear stress without affecting the cyclic variation in
      shear stress. This study demonstrates the feasibility of using noninvasive
      ultrasound techniques in conjunction with CFD to describe time-variant 3D
      hemodynamics in the human carotid arterial bifurcation in vivo.

PMID- 11842027
TI  - Nitric oxide mediates hypoxia-induced cerebral vasodilation in humans.
AB  - Nitric oxide (NO) plays a pivotal role in the regulation of peripheral vascular
      tone. Its role in the regulation of cerebral vascular tone in humans remains to
      be elucidated. This study investigates the role of NO in hypoxia-induced cerebral
      vasodilatation in young healthy volunteers. The effect of the NO synthase
      inhibitor N(G)-monomethyl-L-arginine (L-NMMA) on the cerebral blood flow (CBF)
      was assessed during normoxia and during hypoxia (peripheral O(2) saturation 97
      and 80%, respectively). Subjects were positioned in a magnetic resonance scanner,
      breathing normal air (normoxia) or a N(2)-O(2) mixture (hypoxia). The CBF was
      measured before and after administration of L-NMMA (3 mg/kg) by use of phase
      contrast magnetic resonance imaging techniques. Administration of L-NMMA during
      normoxia did not affect CBF. Hypoxia increased CBF from 1,049 +/- 113 to 1,209 +/
      143 ml/min (P < 0.05). After L-NMMA administration, the augmented CBF returned
      to baseline (1,050 +/- 161 ml/min; P < 0.05). Similarly, cerebral vascular
      resistance declined during hypoxia and returned to baseline after administration
      of L-NMMA (P < 0.05 for both). Use of phase-contrast magnetic resonance imaging
      shows that hypoxia-induced cerebral vasodilatation in humans is mediated by NO.

PMID- 11842028
TI  - Validation of improved recording site to measure phrenic conduction from surface
      electrodes in humans.
AB  - Phrenic nerve stimulation, electrical (ES) or from cervical magnetic stimulation
      (CMS), allows one to assess the diaphragm contractile properties and the
      conduction time of the phrenic nerve (PNCT) through recording of an
      electromyographic response, traditionally by using surface electrodes. Because of
      the coactivation of extradiaphragmatic muscles, signal contamination can
      jeopardize the determination of surface PNCTs. To address this, we compared PNCTs
      with ES and CMS from surface and needle diaphragm electrodes in five subjects (10
      phrenic nerves). At a modified recording site, lower and more anterior than usual
      (lowest accessible intercostal space, costochondral junction) with electrodes 2
      cm apart, surface and needle PNCTs were similar (CMS: 6.0 +/- 0.25 ms surface vs.
      6.2 +/- 0.13 ms needle, not significant). Electrodes recording the activity of
      the most likely sources of signal contamination, i.e., the serratus anterior and
      pectoralis major, showed distinct responses from that of the diaphragm, their
      earlier occurrence strongly arguing against contamination. With ES and CMS,
      apparently uncontaminated signals could be consistently recorded from surface
      electrodes.

PMID- 11842029
TI  - Central dopamine modulates anapyrexia but not hyperventilation induced by
      hypoxia.
AB  - Hypoxia causes hyperventilation and decreases body temperature (T(b)) and
      metabolism [O(2) consumption (VO(2))]. Because dopamine (DA) is released
      centrally in response to peripheral chemoreceptor stimulation, we tested the
      hypothesis that central DA mediates the ventilatory, thermal, and metabolic
      responses to hypoxia. Thus we predicted that injection of haloperidol (a DA D(2)
      receptor antagonist) into the third ventricle would augment hyperventilation and
      attenuate the drop in T(b) and VO(2) in conscious rats. We measured ventilation,
      T(b), and VO(2) before and after intracerebroventricular injection of haloperidol
      or vehicle (5% DMSO in saline), followed by a 30-min period of hypoxia exposure.
      Haloperidol did not change T(b) or VO(2) during normoxia; however, breathing
      frequency was decreased. During hypoxia, haloperidol significantly attenuated the
      falls in T(b) and VO(2), although hyperventilation persisted. The present study
      shows that central DA participates in the thermal and metabolic responses to
      hypoxia without affecting hyperventilation, showing that DA is not a common
      mediator of this interaction.

PMID- 11842030
TI  - Involuntary leg movements affect interstitial nutrient gradients and blood flow
      in rat skeletal muscle.
AB  - To evaluate the effect of passive muscle shortening and lengthening (PSL) on the
      transcapillary exchange of glucose, lactate, and insulin in the insulin
      stimulated state, microdialysis was performed in rat quadriceps muscle.
      Electrical pulsatile stimulation (0.1 ms, 0.3-0.6 V, 1 Hz) was performed on the
      sciatic nerve in one leg to induce passive tension on the quadriceps during a
      hyperinsulinemic-euglycemic clamp (10 mU x kg(-1) x min(-1)). In the non-insulin
      stimulated (basal) state, the muscle arterial-interstitial (A-I) concentration
      difference of glucose was 1.6 +/- 0.3 mM (P < 0.01). During insulin infusion, it
      remained unaltered in resting muscle (1.3 +/- 0.3 mM) but diminished during PSL.
      In the basal state there was no A-I concentration difference of lactate, whereas
      in the insulin infusion state it increased significantly and was significantly
      greater in moving (2.8 +/- 0.5 mM, P < 0.01) than in resting muscle (0.7 +/- 0.4
      mM). The A-I concentration difference of insulin was equal in resting and moving
      muscle: 86 +/- 7 and 100 +/- 8 microU/ml, respectively. Muscle blood flow
      estimated by use of radiolabeled microspheres increased during PSL from 17 +/- 4
      to 34 +/- 6 ml x 100 g(-1) x min(-1) (P < 0.05). These results confirm that
      diffusion over the capillary wall is partly rate limiting for the exchange of
      insulin and glucose and lactate in resting muscle. PSL, in addition to insulin
      stimulation, increases blood flow and capillary permeability and, as a result,
      diminishes the A-I concentration gradient of glucose but not that of insulin or
      lactate.

PMID- 11842031
TI  - Methacholine responsiveness of proximal and distal airways of monkeys and rats
      using videomicrometry.
AB  - Rat and monkey are species that are used in models of human airway
      hyperresponsiveness. However, the wall structures of rat and monkey airways are
      different from each other, with that of the monkey more closely resembling that
      of humans. We hypothesized that differences in wall structure would explain
      differences in airway responsiveness. Using videomicrometry, we measured airway
      luminal area in lung slices to compare proximal and distal airway responsiveness
      to methacholine in the rat and monkey. The airway type was then histologically
      identified. Proximal airways of the young rat and monkey were equally responsive
      to methacholine. In contrast, respiratory bronchioles of monkeys were less
      responsive than were their proximal bronchi, whereas the distal bronchioles of
      rats were more responsive than their proximal bronchioles. Both proximal and
      distal airways of younger monkeys were more responsive than those of older
      monkeys. Airway heterogeneity in young monkeys was greatest with regard to degree
      of airway closure of respiratory bronchioles. We conclude that responsiveness to
      methacholine varies with airway wall structure and location.

PMID- 11842032
TI  - Therapeutic effects of DCDDP, a calcium channel blocker, on chronic pulmonary
      hypertension in rat.
AB  - To explore the effect of dimethyl 4-(2-chlorophenyl)-1,4-dihydro-2,6-dimethyl-3,5
      pyridinedicarboxylate (DCDDP) on pulmonary hypertension (PH) induced by
      monocrotaline (MCT), the parameters of pulmonary hemodynamics, the contents of
      endothelin-like immunoreactivity, nitric oxide (NO), malondialdehyde, and
      superoxide dismutase in plasma and pulmonary homogenate were measured. DCDDP was
      administered in 5, 50, and 500 microg x kg(-1) x day(-1) ip doses, once a day for
      28 days. The antiserotonin effect of DCDDP was investigated by using
      immunohistochemistry, image analysis, and cell culture technique. The results
      showed that pulmonary arterial pressure was significantly dropped and pulmonary
      resistance was decreased in DCDDP groups, compared with the MCT group. DCDDP had
      no influence on endothelin-like immunoreactivity levels in plasma and pulmonary
      homogenate but reduced the contents of NO, superoxide dismutase, and
      malondialdehyde in pulmonary homogenate enhanced by MCT. DCDDP also significantly
      inhibited the increase in numbers of 5-hydroxytryptamine (5-HT) and 5-HT receptor
      positive cells in pulmonary tissue of PH rats induced by MCT. The proliferation
      and contraction of pulmonary arterial smooth muscle cells and the increase in
      concentration of free Ca(2+) in them evoked by 5-HT were inhibited significantly
      by DCDDP. The results suggest that DCDDP reduces the production of free radicals
      and content of 5-HT and 5-HT receptor and the increase in NO in pulmonary tissue,
      which underlies the mechanisms of DCDDP against MCT-induced PH.

PMID- 11842033
TI  - Older adults are less steady during submaximal isometric contractions with the
      knee extensor muscles.
AB  - This study compared the steadiness of submaximal contractions with the knee
      extensor muscles in young and old adults. Twenty young and twenty old subjects
      underwent assessment of isometric maximum voluntary contraction (MVC), one
      repetition maximum (1-RM) strength, and steadiness during isometric, concentric,
      and eccentric contractions with the knee extensor muscles. The old adults
      displayed 33% lower MVC force and a 41% lower 1-RM load. The coefficient of
      variation for force was significantly greater for the old adults during isometric
      contractions at 2, 5, and 10% of MVC but not at 50% MVC. The decline in
      steadiness at low forces experienced by the men was marginally greater than that
      experienced by the women. The steadiness of concentric and eccentric contractions
      was similar in young and old adults at 5, 10, and 50% of 1-RM load. Old subjects
      exhibited greater coactivation of an antagonist muscle compared with young
      subjects during the submaximal isometric and anisometric contractions. These
      results indicate that, whereas the ability to exert steady submaximal forces with
      the knee extensor muscles was reduced in old adults, fluctuations in knee joint
      angle during slow movements were similar for young and old adults.

PMID- 11842034
TI  - Critical developmental period for hyperoxia-induced blunting of hypoxic phrenic
      responses in rats.
AB  - Hypoxic ventilatory and phrenic responses are reduced in adult rats reared in
      hyperoxia (60% O(2)) for the first month of life but not after hyperoxia as
      adults. In this study, we identified the developmental window for susceptibility
      to hyperoxia. Phrenic nerve responses to hypoxia were recorded in anesthetized,
      vagotomized, paralyzed, and ventilated Sprague-Dawley rats (aged 3-4 mo) exposed
      to 60% O(2) for the first, second, third, or fourth postnatal week. Responses
      were compared with control rats and with rats exposed to 60% O(2) for the first
      month of life. Phrenic minute activity (burst amplitude x frequency) increased
      less during isocapnic hypoxia (arterial PO(2) = 60, 50, and 40 Torr) in rats
      exposed to hyperoxia for the first or second week, or the first month, of life (P
      < 0.01 vs. control). Functional impairment caused by 1 wk of hyperoxia diminished
      with increasing age of exposure (P = 0.005). Adult hypoxic phrenic responses are
      impaired by 1 wk of hyperoxia during the first and second postnatal weeks in
      rats, indicating a developmental window coincident with carotid chemoreceptor
      maturation.

PMID- 11842035
TI  - Ozone-induced airway hyperresponsiveness is reduced in immature mice.
AB  - During ozone (O(3)) exposure, adult mice decrease their minute ventilation (VE).
      To determine whether there are age-related differences in the ventilatory
      response to O(3), A/J mice, aged 2, 4, 8, or 12 wk, were exposed to O(3) (0.3-3.0
      parts/million for 3 h) in nose-only exposure plethysmographs. Baseline VE
      normalized for body weight (VE/g) decreased with increasing age, consistent with
      the higher metabolic rates of younger animals. O(3) caused a concentration
      related decrease in VE in mice of all ages, but the response was significantly
      less in 2-wk-old than in older mice. The increased baseline VE/g and smaller
      decrements in VE induced by O(3) in immature mice resulted in an inhaled dose of
      O(3) normalized for body weight that was three to four times higher than in adult
      mice. O(3) exposure caused a dose-related increase in airway responsiveness in 8-
      and 12-wk-old mice but did not cause airway hyperresponsiveness at any dose in
      either 2- or 4-wk-old mice, although higher inhaled doses of O(3) normalized for
      body weight were delivered to these younger animals. Interleukin-6 and macrophage
      inflammatory protein-2 levels in bronchoalveolar lavage fluid were also increased
      in 8-wk-old compared with 2-wk-old mice exposed to O(3). The results suggest that
      immature mice are less sensitive than adult mice to O(3), at least in terms of
      the ability of O(3) to induce airway hyperresponsiveness and promote release of
      certain cytokines.

PMID- 11842036
TI  - Thermal regulation and comfort during a mild-cold exposure in young Japanese
      women complaining of unusual coldness.
AB  - We examined body core and skin temperatures and thermal comfort in young Japanese
      women suffering from unusual coldness (C, n = 6). They were selected by interview
      asking whether they often felt severe coldness even in an air-conditioned
      environment (20-26 degrees C) and compared with women not suffering from coldness
      (N, n = 6). Experiments were conducted twice for each subject: 120-min exposure
      at 23.5 degrees C or 29.5 degrees C after a 40-min baseline at 29.5 degrees C.
      Mean skin temperature decreased (P < 0.05) from 33.6 +/- 0.1 degrees C (mean +/-
      SE) to 31.1 +/- 0.1 degrees C and from 33.5 +/- 0.1 degrees C to 31.1 +/- 0.1
      degrees C in C and N during the 23.5 degrees C exposure. Fingertip temperature in
      C decreased more than in N (P < 0.05; from 35.2 +/- 0.1 degrees C to 23.6 +/- 0.2
      degrees C and from 35.5 +/- 0.1 degrees C to 25.6 +/- 0.6 degrees C). Those
      temperatures during the 29.5 degrees C exposure remained at the baseline levels.
      Rectal temperature during the 23.5 degrees C exposure was maintained at the
      baseline level in both groups (from 36.9 +/- 0.2 degrees C to 36.8 +/- 0.1
      degrees C and 37.1 +/- 0.1 degrees C to 37.0 +/- 0.1 degrees C in C and N). The
      rating scores of cold discomfort for both the body and extremities were greater
      (P < 0.05) in C than in N. Thus the augmented thermal sensitivity of the body to
      cold and activated vasoconstriction of the extremities during cold exposure could
      be the mechanism for the severe coldness felt in C.

PMID- 11842037
TI  - Influence of delayed isotopic equilibration in urine on the accuracy of the
      (2)H(2)(18)O method in the elderly.
AB  - Isotopic determination of total energy expenditure (TEE) by the doubly labeled
      water (DLW) method may be affected by urine retention in the elderly. The
      isotopic enrichments in urine and plasma sampled simultaneously 4 h post-DLW dose
      were compared in a subset of 281 subjects [139 women, 142 men, 75 +/- 3 (SD) yr]
      of the 3,075 participants in the Health, Aging, and Body Composition study. Based
      on analytic precisions, a +/- 2% urine-plasma difference was set as the cut-off
      value. Ten percent of the population presented a difference lower than -2%,
      suggesting a delay in urine isotopic equilibration. This -13 +/- 10% urine-plasma
      difference was not linked to analytic errors, illnesses, the sampling time, or
      the time and quantity of water intake, suggesting that urine retention may be the
      main factor. The consequences are an 18 +/- 13 and 21 +/- 16% overestimation of
      the total body water and the TEE, respectively. Unexpectedly, 21% of the
      population presented a urine-plasma difference higher than +/- 2% that resulted,
      however, in a nonsignificant TEE underestimation of -3 +/- 5%. In conclusion, the
      delayed isotopic equilibration observed in urine reduces the accuracy of the DLW
      method in the elderly. It is recommended, when blood sampling is impossible, to
      adopt the intercept method with urine sampling 24 h postdose.

PMID- 11842038
TI  - Effect of exercise intensity on 24-h energy expenditure and nutrient oxidation.
AB  - The aim of this study was to determine the effects of exercise at different
      intensities on 24-h energy expenditure (EE) and substrate oxidation. Sixteen
      adults (8 men and 8 women) were studied on three occasions [sedentary day (Con),
      a low-intensity exercise day (LI; 400 kcal at 40% of maximal oxygen consumption)
      and a high-intensity exercise day (HI; 400 kcal at 70% of maximal oxygen
      consumption)] by using whole room indirect calorimetry. Both 24-h EE and
      carbohydrate oxidation were significantly elevated on the exercise days (Con < LI
      = HI), but 24-h fat oxidation was not different across conditions. Muscle
      enzymatic profile was not consistently related to 24-h fat or carbohydrate
      oxidation. With further analysis, it was found that, compared with men, women
      sustained slightly higher rates of 24-h fat oxidation (mg x kg FFM(-1) x min(-1))
      and had a muscle enzymatic profile favoring fat oxidation. It is concluded that
      exercise intensity has no effect on 24-h EE or nutrient oxidation. Additionally,
      it appears that women may sustain slightly greater 24-h fat oxidation rates
      during waking and active periods of the day.

PMID- 11842039
TI  - Wall stress misrepresents afterload in children and young adults with abnormal
      left ventricular geometry.
AB  - Wall stress, although commonly used as an index of afterload, fails to take into
      account forces generated within the wall of the left ventricle (LV) that oppose
      systolic fiber shortening. Wall stress may, therefore, misrepresent fiber stress,
      the force resisting fiber shortening, particularly in the presence of an abnormal
      LV thickness-to-dimension ratio (h/D). M-mode LV echocardiograms were obtained
      from 207 patients with a wide range of values for LV mass and/or h/D. Diagnoses
      were valvar aortic stenosis, coarctation repair, anthracycline treated, and
      severe aortic and/or mitral regurgitation. End-systolic wall stress (WS(es)) and
      fiber stress (FS(es)) were expressed as age-corrected Z scores relative to a
      normal population. The difference between WS(es) and FS(es) was extreme when h/D
      was elevated or reduced [WS(es) Z score - FS(es) Z score = 0.14 x (h/D)(-1.47) -
      2.13; r = 0.78, P < 0.001], with WS(es) underestimating FS(es) when h/D was
      increased and overestimating FS(es) when h/D was decreased. Analyses of
      myocardial mechanics based on wall stress have limited validity in patients with
      abnormal ventricular geometry.

PMID- 11842040
TI  - Gene expression of adrenomedullin in failing myocardium: comparison to atrial
      natriuretic peptide.
AB  - The expression of adrenomedullin (AM) and atrial natriuretic factor (ANF) were
      investigated in the myocardium of a rat model of chronic ischemic heart failure
      (CHF) compared with sham-operated controls. In addition, human myocardium of
      patients with end-stage heart failure due to idiopathic dilated cardiomyopathy
      compared with myocardium of normal subjects (NF) was studied. In CHF, similar AM
      levels but increased ANF expression were observed in left ventricular myocardium,
      as assessed by semiquantitative PCR. Functional experiments with freshly excised
      papillary muscles showed no influence of AM on myocardial contractility. In NF
      human myocardium, the expression of AM mRNA was threefold higher in atrial
      compared with ventricular tissue. In analogy, ANF mRNA was increased by
      approximately 15-fold in atrial tissue. In dilated cardiomyopathy, the expression
      of AM was significantly increased in right and left ventricles compared with NF.
      In parallel, ventricular ANF expression was enhanced.

PMID- 11842042
TI  - Effects of postnatal maturation on energetics and cross-bridge properties in rat
      diaphragm.
AB  - The effects of maturation on cross-bridge (CB) properties were studied in rat
      diaphragm strips obtained at postnatal days 3, 10, and 17 and in adults (10-12 wk
      old). Calculations of muscle energetics and characteristics of CBs were
      determined from standard Huxley equations. Maturation did not change the
      curvature of the force-velocity relationship or the peak of mechanical
      efficiency. There was a significant increase in the total number of CBs per cross
      sectional area (m) with aging but not in single CB force. The turnover rate of
      myosin ATPase increased, the duration of the CB cycle decreased, and the velocity
      of CBs decreased significantly only after the first week postpartum. There was a
      linear relationship between maximum total force and m (r = 0.969, P < 0.001), and
      between maximum unloaded shortening velocity and m (r = 0.728, P < 0.001). When
      this study in the rat and previous study in the hamster are compared, it appears
      that there are few species differences in the postnatal maturation process of the
      diaphragm.

PMID- 11842041
TI  - Time- and dose-dependent differential upregulation of three genes by 17 beta
      estradiol in endothelial cells.
AB  - The purpose of this study was to identify genetic targets in the vasculature for
      estrogen by profiling genes expressed in female human aortic endothelial cells
      exposed to various doses of 17 beta-estradiol at differing concentrations and for
      differing periods of time. Our approach employed a RT-PCR-based cloning strategy
      of DNA differential display analysis, with differential expression verified by
      semiquantitative PCR performed with gene-specific primers. A significant increase
      in mRNA expression in response to 17 beta-estradiol was observed for the
      following three genes: aldose reductase (3.4-fold), caspase homologue-alpha
      protein (4.2-fold), and plasminogen activator inhibitor-1 intron e (2.3-fold).
      For all three upregulated genes, estradiol-induced upregulation occurred with a
      similar time course and temporally clustered to the first 24 h after hormone
      treatment. In addition, the effect of estradiol dose on gene expression was
      consistent and occurred at physiological concentrations. Our results describe
      previously uncharacterized estradiol-sensitive time- and dose-dependent
      regulation of genes with potential importance to vascular function in human
      endothelial cells.

PMID- 11842043
TI  - ACE insertion/deletion polymorphism and submaximal exercise hemodynamics in
      postmenopausal women.
AB  - We sought to determine whether the angiotensin-converting enzyme (ACE) insertion
      (I)/deletion (D) polymorphism is associated with submaximal exercise
      cardiovascular hemodynamics. Postmenopausal healthy women (20 sedentary, 20
      physically active, 22 endurance athletes) had cardiac output (acetylene
      rebreathing) measured during 40, 60, and 80% VO(2 max) exercise. The interaction
      of ACE genotype and habitual physical activity (PA) level was significantly
      associated with submaximal exercise systolic blood pressure, with only sedentary
      women exhibiting differences among genotypes. No significant effects of ACE
      genotype or its interaction with PA levels was observed for submaximal exercise
      diastolic blood pressure. ACE genotype was significantly associated with
      submaximal exercise heart rate (HR) with ACE II having approximately 10 beats/min
      higher HR than ACE ID/DD genotype women. ACE genotype did not interact
      significantly with habitual PA level to associate with submaximal exercise HR.
      ACE genotype was not independently, but was interactively with habitual PA
      levels, associated with differences in submaximal exercise cardiac output and
      stroke volume. For cardiac output, ACE II genotype women athletes had ~25%
      greater cardiac output than ACE DD genotype women athletes, whereas for stroke
      volume genotype-dependent differences were observed in both the physically active
      and athletic women. ACE genotype was not significantly associated, either
      independently or interactively with habitual PA levels, with submaximal exercise
      total peripheral resistance or arteriovenous O(2) difference. Thus the common ACE
      locus polymorphic variation is associated with many submaximal exercise
      cardiovascular hemodynamic responses.

PMID- 11842044
TI  - Blood extraction from lancet wounds using vacuum combined with skin stretching.
AB  - Key factors and practical limits of blood extraction from lancet wounds on body
      sites other than the finger were determined by testing a large number of
      conditions. During these tests, the pain associated with lancing alternate body
      sites was rated as less painful than a fingerstick 98% of the time. Vacuum
      combined with skin stretching was effective in extracting an adequate volume of
      blood from the forearm for glucose testing, up to an average of 16 microl in 30
      s. The amount of blood extracted increases with the application of heat or vacuum
      before lancing, the level of vacuum, the depth of lancing, the time of
      collection, and the amount of skin stretching. Vacuum and skin stretching led to
      significant increases, up to fivefold in the perfusion of blood in the skin as
      measured by laser Doppler. Our observations suggest that vacuum combined with
      skin stretching increases blood extraction at alternate sites by increasing the
      lancet wound opening, increasing the blood available for extraction by
      vasodilatation, and reducing the venous return of blood through capillaries.

PMID- 11842045
TI  - Muscle type-specific response of HSP60, HSP72, and HSC73 during recovery after
      elevation of muscle temperature.
AB  - An original method to induce heat stress was used to clarify the time course of
      changes in heat shock proteins (HSPs) in rat skeletal muscles during recovery
      after a single bout of heat stress. One hindlimb was inserted into a stainless
      steel can and directly heated by raising the air temperature inside the can via a
      flexible heater twisted around the steel can. Muscle temperature was increased
      gradually and maintained at 42 degrees C for 60 min. Core rectal and
      contralateral muscle temperatures were increased <1.5 degrees C during the heat
      stress. HSP60, HSP72, and heat shock cognate (HSC) 73 content in the slow soleus
      and fast plantaris in both limbs were determined immediately (0 h) and 2, 4, 8,
      12, 24, 36, 48, or 60 h after heat stress. Within 0-4 h, all HSPs were
      approximately 1.5- to 2.2-fold higher in heat-stressed than contralateral soleus.
      Compared with the contralateral plantaris, the heat-stressed plantaris had a
      higher (1.5-fold) HSP60 content immediately and 2 h after heat stress and a
      higher (2.5- to 6.8-fold) HSP72 content between 24 and 48 h after heat stress.
      Plantaris HSC73 content was not affected by heat stress. This unique heat-stress
      method provides advantages over existing systems; muscle temperature can be
      controlled precisely during heating and the HSP response can be compared between
      muscles in heat-stressed and contralateral limbs of individual rats. Results show
      a differential response of HSPs in the soleus and plantaris during recovery after
      heat stress; soleus demonstrated a more rapid and broader HSP response to heat
      stress than plantaris.

PMID- 11842046
TI  - Damage to different motor units from active lengthening of the medial
      gastrocnemius muscle of the cat.
AB  - Slow-twitch motor units in the medial gastrocnemius muscle of the anesthetized
      cat were found to have an average optimum length for active tension that was 0.8
      +/- 0.5 (SE) mm longer than the whole muscle optimum. For fast-twitch units (time
      to peak < 50 ms), the average optimum was 1.3 +/- 0.3 mm shorter than the whole
      muscle optimum. After the muscle had been subjected to 10 stretches while
      maximally activated, beginning at the whole muscle optimum length, the optimum
      lengths of the 27 fast-twitch motor units shifted significantly further in the
      direction of longer muscle lengths (mean 4.3 +/- 0.3 mm) than for the eight slow
      twitch units (2.1 +/- 0.4 mm). A shift in the muscle's length-tension relation
      was interpreted as being due to sarcomere disruption. Statistical analysis showed
      that a motor unit's optimum length for a contraction, relative to the whole
      muscle optimum, was a better indicator of the unit's susceptibility to damage
      from active lengthenings than was motor unit type.

PMID- 11842047
TI  - Uncoupling protein 3 gene is associated with body composition changes with
      training in HERITAGE study.
AB  - The uncoupling protein 3 (UCP3) is a mitochondrial membrane transporter mainly
      expressed in skeletal muscle that we have shown to be associated with obesity. We
      have analyzed UCP3 polymorphisms, Val102Ile, Tyr210Tyr, and a new microsatellite
      GAIVS6 located in the sixth intron, among 276 black and 503 white subjects from
      the HERITAGE Family Study. Linkage and association studies were undertaken with
      body composition variables measured in a sedentary state (baseline) and after 20
      wk of endurance training (changes). Allele and genotype frequencies were found to
      be significantly different between whites and blacks. Suggestive linkages (0.009
      < or = P < or = 0.033) with Tyr210Tyr were found in blacks and whites for
      baseline body mass index, fat mass, or leptin level and with GAIVS6 in whites for
      changes in fat mass and percent body fat. Associations were also found in whites
      between GAIVS6 and changes in the sum of eight skinfold thicknesses (P = 0.0006),
      with a borderline result for body mass index (P = 0.06). We concluded that UCP3
      could be involved in body composition changes after regular exercise.

PMID- 11842048
TI  - Relationship of airway narrowing, compliance, and cartilage in isolated bronchial
      segments.
AB  - Structural components of the airway wall may act to load airway smooth muscle and
      restrict airway narrowing. In this study, the effect of load on airway narrowing
      was investigated in pig isolated bronchial segments. In some bronchi, pieces of
      cartilage were removed by careful dissection. Airway narrowing was produced by
      maximum electrical field stimulation. An endoscope was used to record lumen
      narrowing. The compliance of the bronchial segments was determined from the cross
      sectional area of the lumen and the transmural pressure. Airway narrowing and the
      velocity of airway narrowing were increased in cartilage-removed airways compared
      with intact control bronchi. Morphometric assessment of smooth muscle length
      showed greater muscle shortening to acetylcholine in cartilage-removed airways
      than in controls. Airway narrowing was positively correlated with airway
      compliance. Compliance and area of cartilage were negatively correlated. These
      results show that airway narrowing is increased in compliant airways and that
      cartilage significantly loads airway smooth muscle in whole bronchi.

PMID- 11842049
TI  - Gender differences in glucose kinetics and substrate oxidation during exercise
      near the lactate threshold.
AB  - The purpose of this investigation was to determine plasma glucose kinetics and
      substrate oxidation in men and women during exercise relative to the lactate
      threshold (LT). Subjects cycled for 25 min at 70 and 90% of O(2) uptake (VO(2))
      at LT (70 and 90% LT, respectively). Plasma glucose appearance (R(a)) and
      disappearance (R(d)) were determined with a primed constant infusion of [6,6
      (2)H]glucose. There were no significant differences in glucose R(a) between men
      [22.6 +/- 1.9 and 39.9 +/- 3.9 micromol x kg fat-free mass (FFM)(-1) x min(-1)
      for 70 and 90% LT, respectively] and women (22.3 +/- 2.7 and 33.9 +/- 5.7
      micromol x kg FFM(-1) x min(-1) for 70 and 90% LT, respectively). Similarly,
      there were no significant differences in glucose R(d) between men (21.2 +/- 1.9
      and 38.1 +/- 3.7 micromol x kg FFM(-1) x min(-1) for 70 and 90% LT, respectively)
      and women (21.3 +/- 2.8 and 33.3 +/- 5.6 micromol x kg FFM(-1) x min(-1) for 70
      and 90% LT, respectively). Although there were no differences between genders in
      the relative contribution of carbohydrate (CHO) to total energy expenditure, the
      relative contribution of muscle glycogen to total CHO oxidation (75.8 +/- 3.2 and
      64.2 +/- 8.0% for men and women, respectively, at 70% LT and 75.1 +/- 2.6 and
      60.1 +/- 11.2% for men and women, respectively, at 90% LT) was lower in women.
      Consequently, the relative contribution of blood glucose to total CHO oxidation
      was significantly higher in women. These results indicate that although plasma
      glucose R(a) and R(d) are similar in men and women, the relative contribution of
      muscle glycogen and blood glucose is significantly different in women during
      moderate-intensity exercise relative to LT.

PMID- 11842050
TI  - Periodic breathing in the mouse.
AB  - The hypothesis was that unstable breathing might be triggered by a brief hypoxia
      challenge in C57BL/6J (B6) mice, which in contrast to A/J mice are known not to
      exhibit short-term potentiation; as a consequence, instability of ventilatory
      behavior could be inherited through genetic mechanisms. Recordings of ventilatory
      behavior by the plethsmography method were made when unanesthetized B6 or A/J
      animals were reoxygenated with 100% O(2) or air after exposure to 8% O(2) or 3%
      CO(2)-10% O(2) gas mixtures. Second, we examined the ventilatory behavior after
      termination of poikilocapnic hypoxia stimuli in recombinant inbred strains
      derived from B6 and A/J animals. Periodic breathing (PB) was defined as clustered
      breathing with either waxing and waning of ventilation or recurrent end
      expiratory pauses (apnea) of > or = 2 average breath durations, each pattern
      being repeated with a cycle number > or = 3. With the abrupt return to room air
      from 8% O(2), 100% of the 10 B6 mice exhibited PB. Among them, five showed
      breathing oscillations with apnea, but none of the 10 A/J mice exhibited cyclic
      oscillations of breathing. When the animals were reoxygenated after 3% CO(2)-10%
      O(2) challenge, no PB was observed in A/J mice, whereas conditions still induced
      PB in B6 mice. (During 100% O(2) reoxygenation, all 10 B6 mice had PB with
      apnea.) Expression of PB occurred in some but not all recombinant mice and was
      not associated with the pattern of breathing at rest. We conclude that
      differences in expression of PB between these strains indicate that genetic
      influences strongly affect the stability of ventilation in the mouse.

PMID- 11842051
TI  - Gasping and autoresuscitation in the developing rat: effect of antecedent
      intermittent hypoxia.
AB  - Gasping is a critically important mechanism for autoresuscitation and survival
      during extreme tissue hypoxia. Evidence of antecedent hypoxia in sudden infant
      death syndrome suggests that intermittently occurring hypoxic episodes may modify
      gasping and autoresuscitation. To examine this issue, an intermittent hypoxia
      (IH) profile consisting of alternating room air and 10% O(2)-balance N(2) every
      90 s was applied to pregnant Sprague-Dawley rats (IHRA; n = 50) and to pups after
      a normal pregnancy (RAIH; n = 50) as well as to control pups (RARA; n = 50). At
      postnatal day 5, pups were exposed to 95% N(2)-5% CO(2), and gasping and the
      ability to autoresuscitate were assessed. Compared with RARA, IHRA- and RAIH
      exposed pups had a reduced number of gasps, decreased overall gasp duration, and
      were less likely to autoresuscitate on introduction of room air to the breathing
      mixture during the last phase of gasping (P < 0.001 vs. RARA). We conclude that
      both prenatal and early postnatal IH adversely affect gasping and related
      survival mechanisms.

PMID- 11842052
TI  - Nonuniform changes in arteriolar myogenic tone within skeletal muscle following
      hindlimb unweighting.
AB  - Hindlimb unweighting (HLU) has been shown to alter myogenic tone distinctly in
      arterioles isolated from skeletal muscles composed predominantly of fast-twitch
      (white gastrocnemius) compared with slow-twitch (soleus) fibers. Based on these
      findings, we hypothesized that HLU would alter myogenic tone differently in
      arterioles isolated from distinct fiber-type regions within a single skeletal
      muscle. We further hypothesized that alterations in myogenic tone would be
      associated with alterations in voltage-gated Ca(2+) channel current (VGCC)
      density of arteriolar smooth muscle. After 14 days of HLU or weight bearing
      (control), first-order arterioles were isolated from both fast-twitch and mixed
      fiber-type regions of the gastrocnemius muscle, cannulated, and pressurized at 90
      cmH(2)O. Mixed gastrocnemius arterioles of HLU rats demonstrated increased
      spontaneous tone [43 +/- 5% (HLU) vs. 27 +/- 4% (control) of possible
      constriction] and an approximately twofold enhanced myogenic response when
      exposed to step changes in intraluminal pressure (10-130 cmH(2)O) compared with
      control rats. In contrast, fast-twitch gastrocnemius arterioles of HLU rats
      demonstrated similar levels of spontaneous tone [6 +/- 2% (HLU) vs. 6 +/- 2%
      (control)] and myogenic reactivity to control rats. Neither KCl-induced
      contractile responses (10-50 mM KCl) nor VGCC density was significantly different
      between mixed gastrocnemius arterioles of HLU and control rats. These results
      suggest that HLU produces diverse adaptations in myogenic reactivity of
      arterioles isolated from different fiber-type regions of a single skeletal
      muscle. Furthermore, alterations in myogenic responses were not attributable to
      altered VGCC density.

PMID- 11842053
TI  - Hypoxia-induced pulmonary endothelin-1 expression is unaltered by nitric oxide.
AB  - Nitric oxide (NO) attenuates hypoxia-induced endothelin (ET)-1 expression in
      cultured umbilical vein endothelial cells. We hypothesized that NO similarly
      attenuates hypoxia-induced increases in ET-1 expression in the lungs of intact
      animals and reasoned that potentially reduced ET-1 levels may contribute to the
      protective effects of NO against the development of pulmonary hypertension during
      chronic hypoxia. As expected, hypoxic exposure (24 h, 10% O(2)) increased rat
      lung ET-1 peptide and prepro-ET-1 mRNA levels. Contrary to our hypothesis,
      inhaled NO (iNO) did not attenuate hypoxia-induced increases in pulmonary ET-1
      peptide or prepro-ET-1 mRNA levels. Because of this surprising finding, we also
      examined the effects of NO on hypoxia-induced increases in ET peptide levels in
      cultured cell experiments. Consistent with the results of iNO experiments,
      administration of the NO donor S-nitroso-N-acetyl-penicillamine to cultured
      bovine pulmonary endothelial cells did not attenuate increases in ET peptide
      levels resulting from hypoxic (24 h, 3% O(2)) exposure. In additional
      experiments, we examined the effects of NO on the activity of a cloned ET-1
      promoter fragment containing a functional hypoxia inducible factor-1 binding site
      in reporter gene experiments. Whereas moderate hypoxia (24 h, 3% O(2)) had no
      effect on ET-1 promoter activity, activity was increased by severe hypoxic (24 h,
      0.5% O(2)) exposure. ET-1 promoter activity after S-nitroso-N-acetyl
      penicillamine administration during severe hypoxia was greater than that in
      normoxic controls, although activity was reduced compared with that in hypoxic
      controls. These findings suggest that hypoxia-induced pulmonary ET-1 expression
      is unaffected by NO.

PMID- 11842054
TI  - Repeated exercise paired with "imperceptible" dead space loading does not alter
      VE of subsequent exercise in humans.
AB  - We employed an associative learning paradigm to test the hypothesis that exercise
      hyperpnea in humans arises from learned responses forged by prior experience.
      Twelve subjects undertook a "conditioning" and a "nonconditioning" session on
      separate days, with order of performance counterbalanced among subjects. In both
      sessions, subjects performed repeated bouts of 6 min of treadmill exercise, each
      separated by 5 min of rest. The only difference between sessions was that all the
      second-to-penultimate runs of the conditioning session were performed with added
      dead space in the breathing circuit. Cardiorespiratory responses during the first
      and last runs (the "control" and "test" runs) were compared for each session.
      Steady-state exercise end-tidal PCO(2) was significantly lower (P = 0.003) during
      test than during control runs for both sessions (dropping by 1.8 +/- 2 and 1.4 +/
      3 Torr during conditioning and nonconditioning sessions, respectively). This and
      all other test-control run differences tended to be greater during the first
      session performed regardless of session type. Our data provide no support for the
      hypothesis implicating associative learning processes in the ventilatory response
      to exercise in humans.

PMID- 11842055
TI  - Mechanical ventilation of isolated rat lungs changes the structure and
      biophysical properties of surfactant.
AB  - Mechanical ventilation is an essential but potentially harmful therapeutic
      intervention for patients with acute lung injury. The objective of this study was
      to investigate the effects of mechanical ventilation on large-aggregate
      surfactant (LA) structure and function. Isolated rat lungs were randomized to
      either a nonventilated control group, a relatively noninjuriously ventilated
      group [1 h, 10 ml/kg tidal volume, 3 cmH(2)O positive end-expiratory pressure
      (PEEP)], or an injuriously ventilated group (1 h, 20 ml/kg tidal volume, 0
      cmH(2)O PEEP). Injurious ventilation resulted in significantly decreased lung
      compliance compared with the other two groups. LA structure, as determined by
      electron microscopy, revealed that LA from the injurious group had significantly
      lower amounts of organized lipid-protein structures compared with LA obtained
      from the other groups. Analysis of the biophysical properties by using a captive
      bubble surfactometer demonstrated that adsorption and surface tension reduction
      were significantly impaired with LA from the injuriously ventilated lungs. We
      conclude that the injurious mechanical ventilation impairs LA function and that
      this impairment is associated with significant morphological alterations.

PMID- 11842056
TI  - Acute ethanol increases angiogenic growth factor gene expression in rat skeletal
      muscle.
AB  - Moderate ethanol consumption demonstrates a protective effect against
      cardiovascular disease and improves insulin sensitivity, possibly through
      angiogenesis. We investigated whether 1) ethanol would increase skeletal muscle
      growth factor gene expression and 2) the effects of ethanol on skeletal muscle
      growth factor gene expression were independent of exercise-induced growth factor
      gene expression. Female Wistar rats were used. Four groups (saline + rest; saline
      + exercise; 17 mmol/kg ethanol + rest; and 17 mmol/kg ethanol + exercise) were
      used to measure the growth factor response to acute exercise and ethanol
      administration. Vascular endothelial growth factor (VEGF), transforming growth
      factor-beta(1) (TGF-beta(1)), basic fibroblast growth factor (bFGF), Flt-1, and
      Flk-1 mRNA were analyzed from the left gastrocnemius by quantitative Northern
      blot. Ethanol increased VEGF, TGF-beta(1), bFGF, and Flt-1 mRNA at rest and after
      acute exercise. Ethanol increased resting Flk-1 mRNA. Ethanol increased bFGF mRNA
      independently of exercise. These findings suggest that 1) ethanol can increase
      skeletal muscle angiogenic growth factor gene expression and 2) the mechanisms
      responsible for the ethanol-induced increases in VEGF, TGF-beta(1), and Flt-1
      mRNA appear to be different from those responsible for exercise-induced
      regulation. Therefore, these results provide evidence in adult rat tissue that
      the protective cardiovascular effects of moderate ethanol consumption may result
      in part through the increase of angiogenic growth factors.

PMID- 11842057
TI  - Pulmonary capillaries are recruited during pulsatile flow.
AB  - Capillaries recruit when pulmonary arterial pressure rises. The duration of
      increased pressure imposed in such experiments is usually on the order of
      minutes, although recent work shows that the recruitment response can occur in <4
      s. In the present study, we investigate whether the brief pressure rise during
      cardiac systole can also cause recruitment and whether the recruitment is
      maintained during diastole. To study these basic aspects of pulmonary capillary
      hemodynamics, isolated dog lungs were pump perfused alternately by steady flow
      and pulsatile flow with the mean arterial and left atrial pressures held
      constant. Several direct measurements of capillary recruitment were made with
      videomicroscopy. The total number and total length of perfused capillaries
      increased significantly during pulsatile flow by 94 and 105%, respectively. Of
      the newly recruited capillaries, 92% were perfused by red blood cells throughout
      the pulsatile cycle. These data provide the first direct account of how the
      pulmonary capillaries respond to pulsatile flow by showing that capillaries are
      recruited during the systolic pulse and that, once open, the capillaries remain
      open throughout the pulsatile cycle.

PMID- 11842058
TI  - Long-term (6-wk) hindlimb suspension inhibits spermatogenesis in adult male rats.
AB  - The International Space Station will allow extended habitation in space and long
      term exposure to microgravity (microG). A concern is the impact of long-term
      microG exposure on the ability of species to reproduce. The model often used to
      simulate microG is rat hindlimb suspension (HLS), where the hindlimbs are
      elevated above the cage floor with a tail harness. Experiments described here are
      the first to examine the effect of long-term HLS on testicular function in adult
      male rats. Free-roaming (controls), animals with only the tail harnessed but
      hindlimbs in contact with the cage floor (TO), and HLS animals were tested for 6
      wk. Cryptorchidism was prevented in TO and HLS animals by partial constriction of
      the inguinal canal with sutures. All parameters were compared at the end of the 6
      wk experiment. Testicular weights and spermatogenesis were significantly reduced
      by HLS, such that no spermatogenic cells beyond round spermatids were present and
      epididymides were devoid of mature sperm. In many tubules, loss of all germ
      cells, except a few spermatogonia, resulting in histopathology similar to the
      Sertoli cell, was observed. Spermatogenesis appeared unaffected in control and TO
      animals. Sertoli and Leydig cell appearance, testosterone, luteinizing hormone,
      and follicle-stimulating hormone levels, and epididymal and seminal vesicle
      weight were unchanged by HLS. Cortisone was not elevated by HLS; thus stress may
      not be a factor. These results demonstrate that spermatogenesis is severely
      inhibited by long-term HLS, whereas testicular androgen production is not. These
      results have significant implications regarding serious effects of long-term
      exposure to microG on the reproductive capability of scrotal mammals, including
      humans.

PMID- 11842059
TI  - A novel rabbit model of variably compensated complete heart block.
AB  - Complete heart block (CHB) provides a useful substrate for study of bradycardia
      dependent ventricular arrhythmias and cardiac function. Existing CHB animal
      models are limited by surgical recovery time and reliance on intrinsic escape
      rhythms. We describe a novel closed-chest rabbit model of CHB involving
      transcatheter radiofrequency (RF) atrioventricular (AV) node ablation and
      ventricular rate control with chronic transvenous pacing. Permanent CHB was
      achieved in 34 of 38 attempts overall. Procedural mortality due to cardiac
      tamponade (n = 2), airway complications (n = 2), and unknown causes (n = 5)
      occurred in nine animals. Survivors with CHB (n = 28) were maintained for < or =
      22 days, during which there were three late deaths related to infection (n = 1)
      or respiratory distress (n = 2). None of the survivors with CHB showed recovery
      of AV conduction or pacemaker capture loss during chronic ventricular pacing at
      about one-half normal sinus rates, and 25 animals surviving to death showed no
      overt signs of hemodynamic compromise such as lethargy, poor feeding, or
      respiratory distress. This approach provides a reproducible nonsurgical CHB model
      with adjustable ventricular rate control.

PMID- 11842060
TI  - Bioenergetic adaptation of individual human diaphragmatic myofibers to severe
      COPD.
AB  - To assess the effect of severe chronic obstructive pulmonary disease (COPD) on
      the ability of human diaphragmatic myofibers to aerobically generate ATP relative
      to ATP utilization, we obtained biopsy specimens of the costal diaphragm from
      seven patients with severe COPD (mean +/- SE; age 56 +/- 1 yr; forced expiratory
      volume in 1 s 23 +/- 2% predicted; residual volume 267 +/- 30% predicted) and
      seven age-matched control subjects. We categorized all fibers in these biopsies
      by using standard techniques, and we carried out the following quantitative
      histochemical measurements by microdensitometry: 1) succinate dehydrogenase (SDH)
      activity as an indicator of mitochondrial oxidative capacity and 2) calcium
      activated myosin ATPase (mATPase) activity, the ATPase that represents a major
      portion of ATP consumption by contracting muscle. We noted the following: 1) COPD
      diaphragms had a larger proportion of type I fibers, a lesser proportion of type
      IIax fibers, and the same proportion of type IIa fibers as controls. 2) SDH
      activities of each of the fiber types were higher in COPD than control diaphragms
      (P < 0.0001); the mean increases (expressed as percent of control values) in
      types I, IIa, and IIax were 84, 114, and 130%, respectively. 3) COPD elicited no
      change in mATPase activity of type I and IIa fibers, but mATPase decreased in
      type IIax fibers (P = 0.02). 4) Mitochondrial oxidative capacity relative to ATP
      demand (i.e., SDH/mATPase) was higher (P = 0.03) in each of the fiber types in
      COPD diaphragms than in controls. These results demonstrate that severe COPD
      elicits an increase in aerobic ATP generating capacity relative to ATP
      utilization in all diaphragmatic fiber types as well as the previously described
      fast-to-slow fiber type transformation (Levine S, Kaiser L, Leferovich J, and
      Tikunov B, N Engl J Med 337: 1799-1806, 1997).

PMID- 11842061
TI  - Development of sex differences in the rabbit masseter muscle is not restricted to
      a critical period.
AB  - The proportions of muscle fibers of different phenotype in the adult rabbit
      masseter differ greatly in different sexes. These sex differences are not
      apparent in young adults, but arise under the influence of testosterone in the
      males. We examined whether this switch occurred during a critical period of
      postnatal development. Testosterone was administered to young adults 1, 2, or 4
      mo after castration, and also to adult females. Samples of masseter muscle were
      taken at four monthly intervals after the onset of treatment and examined for the
      expression of different myosin heavy chain (MyHC) isoforms by using a panel of
      monoclonal antibodies. Despite the length of androgen deprivation, treatment with
      testosterone produced a marked MyHC isoform switch from alpha-slow/beta to IIa.
      This male proportion of fibers of different phenotypes persisted well beyond the
      return of serum testosterone levels to pretreatment levels. Thus brief exposure
      to testosterone produces a permanent change in the proportions of masseter muscle
      fibers of different phenotypes, and the capacity for this change is not
      restricted to a critical period.

PMID- 11842062
TI  - Effect of positive pressure on venous return in volume-loaded cardiac surgical
      patients.
AB  - The hemodynamic effects of increases in airway pressure (Paw) are related in part
      to Paw-induced increases in right atrial pressure (Pra), the downstream pressure
      for venous return, thus decreasing the pressure gradient for venous return.
      However, numerous animal and clinical studies have shown that venous return is
      often sustained during ventilation with positive end-expiratory pressure (PEEP).
      Potentially, PEEP-induced diaphragmatic descent increases abdominal pressure
      (Pabd). We hypothesized that an increase in Paw induced by PEEP would minimally
      alter venous return because the associated increase in Pra would be partially
      offset by a concomitant increase in Pabd. Thus we studied the acute effects of
      graded increases of Paw on Pra, Pabd, and cardiac output by application of
      inspiratory-hold maneuvers in sedated and paralyzed humans. Forty-two patients
      were studied in the intensive care unit after coronary artery bypass surgery
      during hemodynamically stable, fluid-resuscitated conditions. Paw was
      progressively increased in steps of 2 to 4 cmH(2)O from 0 to 20 cmH(2)O in
      sequential 25-s inspiratory-hold maneuvers. Right ventricular (RV) cardiac output
      (CO(td)) and RV ejection fraction (EF(rv)) were measured at 5 s into the
      inspiratory-hold maneuver by the thermodilution technique. RV end-diastolic
      volume and stroke volume were calculated from EF(rv) and heart rate data, and Pra
      was measured from the pulmonary artery catheter. Pabd was estimated as bladder
      pressure. We found that, although increasing Paw progressively increased Pra,
      neither CO(td) nor RV end-diastolic volume changed. The ratio of change (Delta)
      in Paw to Delta Pra was 0.32 +/- 0.20. The ratio of Delta Pra to Delta CO(td) was
      0.05 +/- 00.15 l x min(-1) x mmHg(-1). However, Pabd increased such that the
      ratio of Delta Pra to Delta Pabd was 0.73 +/- 0.36, meaning that most of the
      increase in Pra was reflected in increases in Pabd. We conclude that, in
      hemodynamically stable fluid-resuscitated postoperative surgical patients,
      inspiratory-hold maneuvers with increases in Paw of up to 20 cmH(2)O have minimal
      effects on cardiac output, primarily because of an in-phase-associated
      pressurization of the abdominal compartment associated with compression of the
      liver and squeezing of the lungs.

PMID- 11842063
TI  - Mode shift of an inhaled aerosol bolus is correlated with flow sequencing in the
      human lung.
AB  - We studied the effects on aerosol bolus inhalations of small changes in
      convective inhomogeneity induced by posture change from upright to supine in nine
      normal subjects. Vital capacity single-breath nitrogen washout tests were used to
      determine ventilatory inhomogeneity change between postures. Relative to upright,
      supine phase III slope was increased 33 +/- 11% (mean +/- SE, P < 0.05) and phase
      IV height increased 25 +/- 11% (P < 0.05), consistent with an increase in
      convective inhomogeneity likely due to increases in flow sequencing. Subjects
      also performed 0.5-microm-particle bolus inhalations to penetration volumes
      (V(p)) between 150 and 1,200 ml during a standardized inhalation from residual
      volume to 1 liter above upright functional residual capacity. Mode shift (MS) in
      supine posture was more mouthward than upright at all V(p), changing by 11.6 ml
      at V(p) = 150 ml (P < 0.05) and 38.4 ml at V(p) = 1,200 ml (P < 0.05). MS and
      phase III slope changes correlated positively at deeper V(p). Deposition did not
      change at any V(p), suggesting that deposition did not cause the MS change. We
      propose that the MS change results from increased sequencing in supine vs.
      upright posture.

PMID- 11842064
TI  - Computational modeling of cardiovascular response to orthostatic stress.
AB  - The objective of this study is to develop a model of the cardiovascular system
      capable of simulating the short-term (< or = 5 min) transient and steady-state
      hemodynamic responses to head-up tilt and lower body negative pressure. The model
      consists of a closed-loop lumped-parameter representation of the circulation
      connected to set-point models of the arterial and cardiopulmonary baroreflexes.
      Model parameters are largely based on literature values. Model verification was
      performed by comparing the simulation output under baseline conditions and at
      different levels of orthostatic stress to sets of population-averaged hemodynamic
      data reported in the literature. On the basis of experimental evidence, we
      adjusted some model parameters to simulate experimental data. Orthostatic stress
      simulations are not statistically different from experimental data (two-sided
      test of significance with Bonferroni adjustment for multiple comparisons).
      Transient response characteristics of heart rate to tilt also compare well with
      reported data. A case study is presented on how the model is intended to be used
      in the future to investigate the effects of post-spaceflight orthostatic
      intolerance.

PMID- 11842065
TI  - Oral [(13)C]glucose and endogenous energy substrate oxidation during prolonged
      treadmill running.
AB  - Six male subjects were studied during running exercise (120 min, 69% maximal
      oxygen consumption) with ingestion of a placebo or 3.5 g/kg of [(13)C]glucose
      (approximately 2 g/min). Indirect respiratory calorimetry corrected for urea
      excretion in urine and sweat, production of (13)CO(2) at the mouth, and changes
      in plasma glucose (13)C/(12)C were used to compute energy substrate oxidation.
      The oxidation rate of exogenous glucose increased from 1.02 at minute 60 to 1.22
      g/min at minute 120 providing approximately 24 and 33% of the energy yield (%En).
      Glucose ingestion did not modify protein oxidation, which provided approximately
      4-5%En, but significantly increased glucose oxidation by approximately 7%,
      reduced lipid oxidation by approximately 16%, and markedly reduced endogenous
      glucose oxidation (1.25 vs. 2.21 g/min between minutes 80 and 120, respectively).
      The oxidation rate of glucose released from the liver (0.38 and 0.47 g/min, or 10
      13%En at minutes 60 and 120, respectively), and of plasma glucose (1.30-1.69
      g/min, or 34 and 45%En and 50 and 75% of glucose oxidation) significantly
      increased from minutes 60 to 120, whereas the oxidation of muscle glycogen
      significantly decreased (1.28 to 0.58 g of glucose/min, or 34 and 16%En and 50
      and 25% of glucose oxidation). These results indicate that, during moderate
      prolonged running exercise, ingestion of a very large amount of glucose
      significantly reduces endogenous glucose oxidation, thus sparing muscle and/or
      liver glycogen stores.

PMID- 11842066
TI  - Zero-stress state of intra- and extraparenchymal airways from human, pig, rabbit,
      and sheep lung.
AB  - Alterations in airway wall anatomic properties and the consequential effects on
      airway narrowing have been assessed by use of computational models. In these
      models, it is generally assumed that at zero transmural pressure the airway wall
      exists in a zero-stress state. Many studies have shown that this is often not the
      case, as evidenced by a nonzero opening angle. In this study, we measured the
      opening angle of airway rings at zero transmural pressure to test this
      assumption. The airway tree was dissected from human, pig, sheep, and rabbit
      lungs. Airways were excised from the tree, and the opening angle was measured.
      There were obvious species and regional differences in opening angle. Rabbit
      airways from both extraparenchymal and intraparenchymal sites exhibited marked
      opening angles (7-82 degrees). Extraparenchymal airways from sheep had large
      opening angles (up to 50 degrees), but ovine intraparenchymal airways had small
      opening angles. Measurable opening angles were rarely observed in human and
      porcine airways of any size. The assumption of a stable zero-stress state at zero
      transmural pressure is therefore valid for human and porcine, but not rabbit and
      sheep, airways.

PMID- 11842067
TI  - Low-O(2) affinity erythrocytes improve performance of ischemic myocardium.
AB  - O(2) transport and O(2) diffusion interact in providing O(2) to tissue, but the
      extent to which diffusion may be critical in the heart is unclear. If O(2)
      diffusion limits mitochondrial oxygenation, a change in blood O(2) affinity at
      constant total O(2) transport should alter cardiac O(2) consumption (VO(2)) and
      function. To test this hypothesis, we perfused isolated isovolumically working
      rabbit hearts with erythrocytes at physiological blood-gas values and P(50)
      (PO(2) required to half-saturate hemoglobin) values at pH of 7.4 of 17 +/- 1 Torr
      (2,3-bisphosphoglycerate depletion) and 33 +/- 5 Torr (inositol hexaphosphate
      incorporation). When perfused at 40 and 20% of normal coronary flow, mean VO(2)
      decreased from the control value by 37 and 46% (P < 0.001), and function,
      expressed as cardiac work, decreased by 38 and 52%, respectively (P < 0.001).
      Perfusion at higher P(50) during low-flow ischemia improved VO(2) by 20% (P <
      0.001) and function by 36% (P < 0.02). There was also modest improvement at basal
      flow (P < 0.02 and P < 0.002, respectively). The improvement in VO(2) and
      function due to the P(50) increase demonstrates the importance of O(2) diffusion
      in this cardiac ischemia model.

PMID- 11842068
TI  - Differential CO(2)-induced c-fos gene expression in the nucleus tractus solitarii
      of inbred mouse strains.
AB  - Genetic determinants confer variation between inbred mouse strains with respect
      to the magnitude and pattern of ventilation during hypercapnic challenge.
      Specifically, inheritance patterns derived from low-responsive C3H/HeJ (C3) and
      high-responsive C57BL/6J (B6) mouse strains suggest that differential hypercapnic
      ventilatory sensitivity (HCVS) is controlled by two independent genes. The
      present study also tests whether differential neuronal activity in respiratory
      control regions of the brain is positively associated with strain variation in
      HCVS. With the use of whole body plethysmography, ventilation was assessed in C3
      and B6 strains at baseline and during 30 min of hypercapnia (inspired CO(2)
      fraction = 0.15, inspired O(2) fraction = 0.21 in N(2)). Subsequently, in situ
      hybridization histochemistry was performed to determine changes in c-fos gene
      expression in the commissural subnucleus of the nucleus tractus solitarius (NTS).
      During hypercapnia, breathing frequency and tidal volume were significantly (P <
      0.01) different between strains: C3 mice showed a slow, deep-breathing pattern
      relative to a rapid, shallow phenotype of B6 mice. CO(2)-induced increase in c
      fos gene expression was significantly (P < 0.01) greater in NTS regions of B6
      compared with C3 mice. In this genetic model of differential HCVS, the results
      suggest that a genomic basis for varied hypercapnic chemoreception or
      transduction confers greater afferent neuronal activity in the caudal NTS for
      high-responsive B6 mice compared with low-responsive C3 mice.

PMID- 11842069
TI  - Clenbuterol prevents epinephrine from antagonizing insulin-stimulated muscle
      glucose uptake.
AB  - In the present study, we investigated the effects of chronic clenbuterol
      treatment on insulin-stimulated glucose uptake in the presence of epinephrine in
      isolated rat skeletal muscle. Insulin (50 microU/ml) increased glucose uptake in
      both fast-twitch (epitrochlearis) and slow-twitch (soleus) muscles. In the
      presence of 24 nM epinephrine, insulin-stimulated glucose uptake was completely
      suppressed. This suppression of glucose uptake by epinephrine was accompanied by
      an increase in the intracellular concentration of glucose 6-phosphate and a
      decrease in insulin-receptor substrate-1-associated phosphatidylinositol 3-kinase
      (IRS-1/PI3-kinase) activity. Clenbuterol treatment had no direct effect on
      insulin-stimulated glucose uptake. However, after clenbuterol treatment,
      epinephrine was ineffective in attenuating insulin-stimulated muscle glucose
      uptake. This ineffectiveness of epinephrine to suppress insulin-stimulated
      glucose uptake occurred in conjunction with its inability to increase the
      intracellular concentration of glucose 6-phosphate and attenuate IRS-1/PI3-kinase
      activity. Results of this study indicate that the effectiveness of epinephrine to
      inhibit insulin-stimulated glucose uptake is severely diminished in muscle from
      rats pretreated with clenbuterol.

PMID- 11842070
TI  - Effects of pH on the length-dependent twitch potentiation in skeletal muscle.
AB  - When muscle is elongated, there is a length dependence of twitch potentiation and
      an increased Ca(2+) sensitivity of the myofilaments. Changes in the charge
      potential of myofilaments, induced by a decrease in pH, are known to abolish the
      length dependence of Ca(2+) sensitivity. This study was aimed at testing the
      hypothesis that a decrease in pH, and the concomitant loss of length dependence
      of Ca(2+) sensitivity, depresses the length dependence of staircase potentiation.
      In vitro, isometric twitch contractions of fiber bundles dissected from the mouse
      extensor digitorum longus, performed before and after 10 s of 10-Hz stimulation
      (i.e., the staircase potentiation protocol) were analyzed at five different
      lengths, ranging from optimal length for maximal force production (L(o); = 12 +/-
      0.7 mm) to L(o) + 1.2 mm (L(o) + 10%). These measurements were made at an
      extracellular pH of 6.6, 7.4, and 7.8 (pH changes induced by altering the CO(2)
      concentration of the bath solution). At pH 7.4 and 7.8, the degree of
      potentiation after 10-Hz stimulation showed a linear decrease with increased
      fiber bundle length (r(2) = 0.95 and r(2) = 0.99, respectively). At pH 6.6, the
      length dependence of potentiation was abolished, and the slope of the length
      potentiation relationship was not different from zero (r(2) = 0.05). The results
      of this study indicate that length dependence of potentiation in intact skeletal
      muscle is abolished by lowering the pH. Because decreasing the pH decreases
      Ca(2+) sensitivity and changes the charge potential of the filaments, the
      mechanism of length-dependent potentiation may be closely related to the length
      dependence of Ca(2+) sensitivity, and changes in the charge potential of the
      myofilaments may be important in regulating this relationship.

PMID- 11842071
TI  - Effect of exercise training at different intensities on fat metabolism of obese
      men.
AB  - The present study investigated the effect of exercise training at different
      intensities on fat oxidation in obese men. Twenty-four healthy male obese
      subjects were randomly divided in either a low- [40% maximal oxygen consumption
      (VO(2 max))] or high-intensity exercise training program (70% VO(2 max)) for 12
      wk, or a non-exercising control group. Before and after the intervention,
      measurements of fat metabolism at rest and during exercise were performed by
      using indirect calorimetry, [U-(13)C]palmitate, and [1,2-(13)C]acetate.
      Furthermore, body composition and maximal aerobic capacity were measured. Total
      fat oxidation did not change at rest in any group. During exercise, after low
      intensity exercise training, fat oxidation was increased by 40% (P < 0.05)
      because of an increased non-plasma fatty acid oxidation (P < 0.05). High
      intensity exercise training did not affect total fat oxidation during exercise.
      Changes in fat oxidation were not significantly different among groups. It was
      concluded that low-intensity exercise training in obese subjects seemed to
      increase fat oxidation during exercise but not at rest. No effect of high
      intensity exercise training on fat oxidation could be shown.

PMID- 11842072
TI  - Lipolysis in human adipose tissue during exercise: comparison of microdialysis
      and a-v measurements.
AB  - Subcutaneous adipose tissue lipolysis was studied in vivo by Fick's arteriovenous
      (a-v) principle using either calculated (microdialysis) or directly measured
      (catheterization) adipose tissue venous glycerol concentration. We compared
      results during steady-state (rest and prolonged continuous exercise), as well as
      during non-steady-state (onset of exercise and early exercise) experimental
      settings. Fourteen healthy women [age: 74 +/- 1 (SE) yr] were studied at rest and
      during 60-min continuous bicycling at 60% of peak O(2) uptake. Calculated and
      measured subcutaneous abdominal adipose tissue venous glycerol concentrations
      increased substantially from rest to exercise but were similar both at rest and
      during later stages of exercise. In contrast, during the initial approximately 40
      min of exercise, calculated glycerol concentration was significantly lower
      (approximately 40%) than measured adipose tissue venous glycerol concentration.
      Despite several methodological limitations inherent to both techniques, the
      results strongly suggest that microdialysis and catheterization provide similar
      estimates of subcutaneous adipose tissue lipolysis in steady-state experimental
      settings like rest and continuous prolonged exercise. However, during shorter
      periods of exercise (<40 min), the results from the two techniques may differ
      quantitatively in the studied subjects. Caution should, therefore, be taken when
      lipolysis is evaluated, based on results obtained by the two techniques under non
      steady-state conditions.

PMID- 11842073
TI  - Brain activation by central command during actual and imagined handgrip under
      hypnosis.
AB  - The purpose was to compare patterns of brain activation during imagined handgrip
      exercise and identify cerebral cortical structures participating in "central"
      cardiovascular regulation. Subjects screened for hypnotizability, five with
      higher (HH) and four with lower hypnotizability (LH) scores, were tested under
      two conditions involving 3 min of 1) static handgrip exercise (HG) at 30% of
      maximal voluntary contraction (MVC) and 2) imagined HG (I-HG) at 30% MVC. Force
      (kg), forearm integrated electromyography, rating of perceived exertion, heart
      rate (HR), mean blood pressure (MBP), and differences in regional cerebral blood
      flow distributions were compared using an ANOVA. During HG, both groups showed
      similar increases in HR (+13 +/- 5 beats/min) and MBP (+17 +/- 3 mmHg) after 3
      min. However, during I-HG, only the HH group showed increases in HR (+10 +/- 2
      beats/min; P < 0.05) and MBP (+12 +/- 2 mmHg; P < 0.05). There were no
      significant increases or differences in force or integrated electromyographic
      activity between groups during I-HG. The rating of perceived exertion was
      significantly increased for the HH group during I-HG, but not for the LH group.
      In comparison of regional cerebral blood flow, the LH showed significantly lower
      activity in the anterior cingulate (-6 +/- 2%) and insular cortexes (-9 +/- 4%)
      during I-HG. These findings suggest that cardiovascular responses elicited during
      imagined exercise involve central activation of insular and anterior cingulate
      cortexes, independent of muscle afferent feedback; these structures appear to
      have key roles in the central modulation of cardiovascular responses.

PMID- 11842074
TI  - Femoral artery inflow in relation to external and total work rate at different
      knee extensor contraction rates.
AB  - Whether limb blood flow is directly regulated to match the work rate, independent
      of the rate of contraction, remains elusive. This study therefore investigated
      the relationship between femoral arterial blood flow (FABF; Doppler ultrasound)
      and "external" (applied load) as well as "total" [external + "internal"
      (potential and kinetic energy changes of the moving lower leg)] work rate, during
      steady-state one-legged, dynamic, knee extensor exercise (1L-KEE) in the sitting
      position at different contraction rates. Ten subjects performed 1L-KEE at 30, 60,
      and 90 contractions/min (cpm) 1) at constant resistive loads of 0.2 and 0.5 kg
      inducing incremental external work rates (study I) and 2) at different relative
      resistive loads inducing constant external work rates of 9 and 18 W (study II).
      Moreover, 3) six subjects performed 1L-KEE at 60 and 100 cpm at incremental total
      work rates of 40, 50, 60, and 70 W (study III). In study I, FABF increased (P <
      0.001) with increasing contraction frequency and external work rate, for each
      resistive load. In study II, FABF increased (P < 0.001) with increasing
      contraction frequency for each constant external work rate. Of major importance
      in study III, however, was that FABF, although increasing linearly with the total
      work rate, was not different (P = not significant) between contraction rates, at
      the total work rates of 40, 50, 60, and 70 W, respectively. Furthermore, FABF
      correlated linearly and positively with both the external and total work rate for
      each contraction frequency. In conclusion, the findings support the concept that
      leg blood flow during 1L-KEE in a normal knee extensor ergometer is matched
      directly in relation to the total work rate and metabolic activity, irrespective
      of the contraction frequency. The rate of contraction seems erroneously to
      influence the results only when it is related to the external work rate without
      taking into account the internal work component.

PMID- 11842075
TI  - Biopsy coupled to quantitative immunofluorescence: a new method to study the
      human vascular endothelium.
AB  - Limited availability of endothelial tissue is a major constraint when
      investigating the cellular mechanisms of endothelial dysfunction in patients with
      metabolic and cardiovascular diseases. We propose a novel approach that combines
      collection of 200-1,000 endothelial cells from a superficial forearm vein or the
      radial artery, with reliable measurements of protein expression by quantitative
      immunofluorescence analysis. This method was validated against immunoblot
      analysis in cultured endothelial cells. Levels of vascular endothelial cell
      activation, oxidative stress, and nitric oxide synthase expression were measured
      and compared in five patients with severe chronic heart failure and in four
      healthy age-matched subjects. In summary, vascular endothelial biopsy coupled
      with measurement of protein expression by quantitative immunofluorescence
      analysis provides a novel approach to the study of the vascular endothelium in
      humans.

PMID- 11842076
TI  - Invited review: genetic dissection of sleep.
AB  - Recent advances in genomics open up new avenues in the analysis of complex
      behaviors such as sleep. In this analysis, the mouse is the model species of
      choice because it is amenable to high throughput phenotype and genotype analysis.
      With the use of the mouse model, unprecedented progress in our understanding of
      sleep physiology and the treatment of sleep disorders is awaited. This review is
      intended to provide an overview of available methods and techniques for genetic
      dissection of sleep in mice. Limits and advantages of different approaches are
      discussed to highlight the necessity for combining methods to avoid erroneous
      interpretations. The gap between understanding mechanisms of sleep and its
      functions may be bridged by finding its molecular bases.

PMID- 11842077
TI  - Invited review: regulation of mammalian circadian clock genes.
AB  - The circadian clock is a self-sustaining oscillator that has a period of
      approximately 24 h and controls many physiological and behavioral systems. This
      clock can synchronize itself to changing environmental conditions to optimize an
      organisms performance. The underlying circadian rhythms are generated by periodic
      activation of transcription by a set of clock genes. Besides their own
      regulation, clock genes can influence biochemical processes by modulating
      specific genes of biochemical pathways. Developments in the last few years using
      genetics and molecular biological tools have led to a new understanding of the
      molecular basis of the circadian clock in mammals. In this mini-review, I will
      summarize these advances that have led us to begin understanding the mammalian
      circadian clock at the molecular level.

PMID- 11842079
TI  - Selected contribution: circadian rhythm of tumor necrosis factor-alpha uptake
      into mouse spinal cord.
AB  - Circadian variations in the actions of tumor necrosis factor-alpha (TNF-alpha)
      have been observed. Because a saturable transport system at the blood-brain
      barrier mediates most of the influx of TNF-alpha from blood to the central
      nervous system (CNS), the circadian variation of the CNS effects of TNF-alpha
      could be related to changes in this transport system. Accordingly, we measured
      the uptake of intravenously injected TNF-alpha into various CNS regions at
      different times and compared these measurements with the uptake into a peripheral
      control (muscle). We found that the spinal cord, but not the brain, showed a
      circadian rhythm in the uptake of TNF-alpha. This pattern is similar to that of
      leptin but different from that of interleukin-1. The circadian rhythm of the
      influx of TNF-alpha into this region of the CNS suggests a functional role for
      the spinal cord in the physiological actions of TNF-alpha.

PMID- 11842080
TI  - Structural requirements within the lipoyl domain for the Ca2+-dependent binding
      and activation of pyruvate dehydrogenase phosphatase isoform 1 or its catalytic
      subunit.
AB  - The inner lipoyl domain (L2) of the dihydrolipoyl acetyltransferase (E2) 60-mer
      forms a Ca(2+)-dependent complex with the pyruvate dehydrogenase phosphatase 1
      (PDP1) or its catalytic subunit, PDP1c, in facilitating large enhancements of the
      activities of PDP1 (10-fold) or PDP1c (6-fold). L2 binding to PDP1 or PDP1c
      requires the lipoyl-lysine prosthetic group and specificity residues that
      distinguish L2 from the other lipoyl domains (L1 in E2 and L3 in the E3-binding
      component). The L2-surface structure contributing to binding was mapped by
      comparing the capacities of well folded mutant or lipoyl analog-substituted L2
      domains to interfere with E2 activation by competitively binding to PDP1 or
      PDP1c. Our results reveal the critical importance of a regional set of residues
      near the lipoyl group and of the octanoyl but not the dithiolane ring structure
      of the lipoyl group. At the other end of the lipoyl domain, substitution of
      Glu(182) by alanine or glutamine removed L2 binding to PDP1 or PDP1c, and these
      substitutions for the neighboring Glu(179) also greatly hindered complex
      formation (E179A > E179Q). Among 11 substitutions in L2 at sites of major surface
      residue differences between the L1 and L2 domains, only the conversion of Val
      Gln(181) located between the critical Glu(179) and Glu(182) to the aligned Ser
      Leu sequence of the L1 domain greatly reduced L2 binding. Certain modified L2
      altered E2 activation of PDP1 differently than PDP1c, supporting significant
      impact of the regulatory PDP1r subunit on PDP1 binding to L2. Our results
      indicate hydrophobic binding via the extended aliphatic structure of the lipoyl
      group and required adjacent L2 structure anchor PDP1 by acting in concert with an
      acidic cluster at the other end of the domain.

PMID- 11842081
TI  - The phosphatidylinositol 3-kinase (PI3K)-Akt pathway suppresses Bax translocation
      to mitochondria.
AB  - Bax, a proapoptotic member of the Bcl-2 family, localizes largely in the
      cytoplasm but redistributes to mitochondria in response to apoptotic stimuli,
      where it induces cytochrome c release. In this study, we show that the
      phosphatidylinositol 3-OH kinase (PI3K)-Akt pathway plays an important role in
      the regulation of Bax subcellular localization. We found that LY294002, a PI3K
      inhibitor, blocked the effects of serum to prevent Bax translocation to
      mitochondria and that expression of an active form of PI3K suppressed
      staurosporine-induced Bax translocation, suggesting that PI3K activity is
      essential for retaining Bax in the cytoplasm. In contrast, both U0126, a MEK
      inhibitor, and active MEK had little effect on Bax localization. In respect to
      downstream effectors of PI3K, we found that expression of active Akt, but not
      serum and glucocorticoid-induced protein kinase (SGK), suppressed staurosporine
      induced translocation of Bax, whereas dominant negative Akt moderately promoted
      Bax translocation. Expression of Akt did not alter the levels of Bax, Bcl-2, Bcl
      X(L), or phosphorylated JNK under the conditions used, suggesting that there were
      alternative mechanisms for Akt in the suppression of Bax translocation.
      Collectively, these results suggest that the PI3K-Akt pathway inhibits Bax
      translocation from cytoplasm to mitochondria and have revealed a novel mechanism
      by which the PI3K-Akt pathway promotes survival.

PMID- 11842082
TI  - Activation of the inositol 1,4,5-trisphosphate receptor by the calcium storage
      protein chromogranin A.
AB  - Secretory granules of neuroendocrine cells are inositol 1,4,5-trisphosphate
      (InsP(3))-sensitive Ca(2+) stores in which the Ca(2+) storage protein,
      chromogranin A (CGA), couples with InsP(3)-gated Ca(2+) channels (InsP(3)R)
      located in the granule membrane. The functional aspect of this coupling has been
      investigated via release studies and planar lipid bilayer experiments in the
      presence and absence of CGA. CGA drastically increased the release activity of
      the InsP(3)R by increasing the channel open probability by 9-fold and the mean
      open time by 12-fold. Our results show that CGA-coupled InsP(3)Rs are more
      sensitive to activation than uncoupled receptors. This modulation of InsP(3)R
      channel activity by CGA appears to be an essential component in the control of
      intracellular Ca(2+) concentration by secretory granules and may regulate the
      rate of vesicle fusion and exocytosis.

PMID- 11842084
TI  - Haemophilus influenzae type b strain A2 has multiple sialyltransferases involved
      in lipooligosaccharide sialylation.
AB  - The lipooligosaccharide (LOS) of Haemophilus influenzae contains sialylated
      glycoforms, and a sialyltransferase, Lic3A, has been previously identified. We
      report evidence for two additional sialyltransferases, SiaA, and LsgB, that
      affect N-acetyllactosamine containing glycoforms. Mutations in genes we have
      designated siaA and lsgB affected only the sialylated glycoforms containing N
      acetylhexosamine. A mutation in siaA resulted in the loss of glycoforms
      terminating in sialyl-N-acetylhexosamine and the appearance of higher molecular
      weight glycoforms, containing the addition of phosphoethanolamine, N
      acetylgalactosamine, and N-acetylneuraminic acid. Chromosomal complementation of
      the siaA mutant resulted in the expression of the original sialylated LOS
      phenotype. A mutation in lic3A resulted in the loss of sialylation only in
      glycoforms lacking N-acetylhexosamine and had no effect on sialylation of the
      terminal N-acetyllactosamine epitope. A double mutant in siaA and lic3A resulted
      in the complete loss of sialylation of the terminal N-acetyllactosamine epitope
      and expression of the higher molecular weight sialylated glycoforms seen in the
      siaA mutant. Mutation of lsgB resulted in persistence of sialylated glycoforms
      but a reduction in N-acetyllactosamine containing glycoforms. A triple mutant of
      siaA, lic3A, and lsgB contained no sialylated glycoforms. These results
      demonstrate that the sialylation of the LOS of H. influenzae is a complex process
      involving multiple sialyltransferases.

PMID- 11842083
TI  - The insulin-sensitive glucose transporter, GLUT4, interacts physically with Daxx.
      Two proteins with capacity to bind Ubc9 and conjugated to SUMO1.
AB  - In this study we have used the yeast two-hybrid system to identify proteins that
      interact with the carboxyl-cytoplasmic domain (residues 464-509) of the insulin
      sensitive glucose transporter GLUT4 (C-GLUT4). Using as bait C-GLUT4, we have
      isolated the carboxyl domain of Daxx (C-Daxx), the adaptor protein associated
      with the Fas and the type II TGF-beta (TbetaRII) receptors (1,2 ). The two-hybrid
      interaction between C-GLUT4 and C-Daxx is validated by the ability of in vitro
      translated C-GLUT4 to interact with in vitro translated full-length Daxx and C
      Daxx. C-Daxx does not interact with the C-cytoplasmic domain of GLUT1, the
      ubiquitous glucose transporter homologous to GLUT4. Replacement of alanine and
      serine for the dileucine pair (Leu(489)-Leu(490)) critical for targeting GLUT4
      from the trans-Golgi network to the perinuclear intracellular store as well as
      for its surface internalization by endocytosis inhibits 2-fold the interaction of
      C-GLUT4 with Daxx. Daxx is pulled down with GLUT4 immunoprecipitated from lysates
      of 3T3-L1 fibroblasts stably transfected with GLUT4 and 3T3-L1 adipocytes
      expressing physiological levels of the two proteins. Similarly, GLUT4 is
      recovered with anti-Daxx immunoprecipitates. Using an established cell
      fractionation procedure we present evidence for the existence of two distinct
      intracellular Daxx pools in the nucleus and low density microsomes. Confocal
      immunofluorescence microscopy studies localize Daxx to promyelocytic leukemia
      nuclear bodies and punctate cytoplasmic structures, often organized in strings
      and underneath the plasma membrane. Daxx and GLUT4 are SUMOlated as shown by
      their reaction with an anti-SUMO1 antibody and by the ability of this antibody to
      pull down Daxx and GLUT4.

PMID- 11842085
TI  - The Trypanosoma cruzi enzyme TcGPXI is a glycosomal peroxidase and can be linked
      to trypanothione reduction by glutathione or tryparedoxin.
AB  - Trypanosoma cruzi glutathione-dependent peroxidase I (TcGPXI) can reduce fatty
      acid, phospholipid, and short chain organic hydroperoxides utilizing a novel
      redox cycle in which enzyme activity is linked to the reduction of trypanothione,
      a parasite-specific thiol, by glutathione. Here we show that TcGPXI activity can
      also be linked to trypanothione reduction by an alternative pathway involving the
      thioredoxin-like protein tryparedoxin. The presence of this new pathway was first
      detected using dialyzed soluble fractions of parasite extract. Tryparedoxin was
      identified as the intermediate molecule following purification, sequence
      analysis, antibody studies, and reconstitution of the redox cycle in vitro. The
      system can be readily saturated by trypanothione, the rate-limiting step being
      the interaction of trypanothione with the tryparedoxin. Both tryparedoxin and
      TcGPXI operate by a ping-pong mechanism. Overexpression of TcGPXI in transfected
      parasites confers increased resistance to exogenous hydroperoxides. TcGPXI
      contains a carboxyl-terminal tripeptide (ARI) that could act as a targeting
      signal for the glycosome, a kinetoplastid-specific organelle. Using
      immunofluorescence, tagged fluorescent proteins, and biochemical fractionation,
      we have demonstrated that TcGPXI is localized to both the glycosome and the
      cytosol. The ability of TcGPXI to use alternative electron donors may reflect
      their availability at the corresponding subcellular sites.

PMID- 11842086
TI  - HSP70 as endogenous stimulus of the Toll/interleukin-1 receptor signal pathway.
AB  - Human heat-shock protein (HSP)70 activates innate immune cells and hence requires
      no additional adjuvants to render bound peptides immunogenic. Here we tested the
      assumption that endogenous HSP70 activates the Toll/IL-1 receptor signal pathway
      similar to HSP60 and pathogen-derived molecular patterns. We show that HSP70
      induces interleukin-12 (IL-12) and endothelial cell-leukocyte adhesion molecule-1
      (ELAM-1) promoters in macrophages and that this is controlled by MyD88 and TRAF6.
      Furthermore, HSP70 causes MyD88 relocalization and MyD88-deficient dendritic
      cells do not respond to HSP70 with proinflammatory cytokine production. Using the
      system of genetic complementation with Toll-like receptors (TLR) we found that
      TLR2 and TLR4 confer responsiveness to HSP70 in 293T fibroblasts. The expanding
      list of endogenous ligands able to activate the ancient Toll/IL-1 receptor signal
      pathway is in line with the "danger hypothesis" proposing that the innate immune
      system senses danger signals even if they originate from self.

PMID- 11842087
TI  - Complete hemocyanin subunit sequences of the hunting spider Cupiennius salei:
      recent hemocyanin remodeling in entelegyne spiders.
AB  - Hemocyanins are large copper-containing respiratory proteins found in many
      arthropod species. Scorpions and orthognath spiders possess a highly conserved 4
      x 6-mer hemocyanin that consists of at least seven distinct subunit types (termed
      a to g). However, many "modern" entelegyne spiders such as Cupiennius salei
      differ from the standard arachnid scheme and have 2 x 6-mer hemocyanins. Here we
      report the complete primary structure of the 2 x 6-mer hemocyanin of C. salei as
      deduced from cDNA sequencing, gel electrophoresis, and matrix-assisted laser
      desorption spectroscopy. Six distinct subunit types (1 through 6) and three
      additional allelic sequences were identified. Each 1 x 6-mer half-molecule most
      likely is composed of subunits 1-6, with subunit 1 linking the two hexamers via a
      disulfide bridge located in a C-terminal extension. The C. salei hemocyanin
      subunits all belong to the arachnid g-type, whereas the other six types (a-f)
      have been lost in evolution. The reconstruction of a complex hemocyanin from a
      single g-type subunit, which commenced about 190 million years ago and was
      completed about 90 million years ago, might be explained by physiological and
      behavioral changes that occurred during the evolution of the entelegyne spiders.

PMID- 11842088
TI  - Cross-talk between ERK and p38 MAPK mediates selective suppression of pro
      inflammatory cytokines by transforming growth factor-beta.
AB  - Phagocytosis of apoptotic cells by macrophages results in the production of
      transforming growth factor-beta (TGF-beta), which plays an important role in
      induction of an anti-inflammatory phenotype and resolution of inflammation. In
      this study, we show that TGF-beta prevents pro-inflammatory cytokine production
      through inhibition of p38 mitogen-activated protein kinase (MAPK) and NF-kappaB.
      Blockade of extracellular signal-regulated kinase (ERK) signaling by the MEK-1/2
      inhibitor PD 98059 reversed the inhibitory effects of TGF-beta, suggesting that
      cross-talk between MAPKs is essential for this response. Further investigation
      indicated that TGF-beta activated ERK, which in turn up-regulated MAPK
      phosphatase-1, thereby inactivating p38 MAPK. On the other hand, TGF-beta
      maintained or slightly increased production of the CC chemokine MCP-1, which is
      regulated predominantly by AP-1. Although SB 203580, an inhibitor of p38 MAPK,
      and dominant-negative p38 MAPK both increased AP-1 transcription, lack of effect
      of TGF-beta on lipopolysaccharide-stimulated SAPK/JNK phosphorylation along with
      a demonstrated inhibition of TGF-beta-induced AP-1 activation by dominant
      negative Smad3 suggest that TGF-beta-stimulated AP-1 activation was not caused by
      inhibition of p38 MAPK but rather through the activation of Smads. Our data
      provide evidence that TGF-beta selectively inhibits inflammatory cytokine
      production through cross-talk between MAPKs.

PMID- 11842089
TI  - Increased expression of dihydrodiol dehydrogenase induces resistance to cisplatin
      in human ovarian carcinoma cells.
AB  - We employed cDNA microarrays to identify the differentially expressed genes in a
      cisplatin-sensitive parental (2008) human ovarian carcinoma cell line and its
      cisplatin-resistant variant (2008/C13*). Differential expression of five genes
      was found in the 2008/C13* cells, a result confirmed by semi-quantitative reverse
      transcription-PCR. The five genes were identified as fibroblast muscle-type
      tropomyosin and skeletal muscle-type tropomyosin, dihydrodiol dehydrogenase,
      apolipoprotein J and glucose-6-phosphate dehydrogenase variant-A. Treatment of
      the 2008 cells with cisplatin (at its IC(50) concentration of 2 microm) induced
      expression of these genes, as determined by semi-quantitative reverse
      transcription-PCR analysis using gene-specific primers. In contrast, treatment of
      the drug-resistant 2008/C13* cells with cisplatin (at its IC(50) concentration of
      20 microm) did not lead to the induction of any of the aforementioned genes. Most
      importantly, constitutive overexpression of dihydrodiol dehydrogenase (but not
      the other genes) in the 2008 cells led to induction of cisplatin resistance,
      clearly indicating its role in the development of the resistance phenotype in the
      2008/C13* cells. The development of cisplatin resistance in the transfected cells
      was associated with an increase in the dihydrodiol dehydrogenase enzyme activity.
      Although at present it is not clear how dihydrodiol dehydrogenase is involved in
      cisplatin resistance, the identification of this gene as a causal factor suggests
      the existence of a hitherto undefined pathway resulting in cisplatin resistance.

PMID- 11842090
TI  - The crystal structure of the allosteric non-phosphorylating glyceraldehyde-3
      phosphate dehydrogenase from the hyperthermophilic archaeum Thermoproteus tenax.
AB  - The NAD(+)-dependent non-phosphorylating glyceraldehyde-3-phosphate dehydrogenase
      (GAPN) from the hyperthermophilic archaeum Thermoproteus tenax represents an
      archaeal member of the diverse superfamily of aldehyde dehydrogenases (ALDHs).
      GAPN catalyzes the irreversible oxidation of d-glyceraldehyde 3-phosphate to 3
      phosphoglycerate. In this study, we present the crystal structure of GAPN in
      complex with its natural inhibitor NADP(+) determined by multiple anomalous
      diffraction methods. The structure was refined to a resolution of 2.4 A with an R
      factor of 0.21. The overall fold of GAPN is similar to the structures of ALDHs
      described previously, consisting of three domains: a nucleotide-binding domain, a
      catalytic domain, and an oligomerization domain. Local differences in the active
      site are responsible for substrate specificity. The inhibitor NADP(+) binds at an
      equivalent site to the cosubstrate-binding site of other ALDHs and blocks the
      enzyme in its inactive state, possibly preventing the transition to the active
      conformation. Structural comparison between GAPN from the hyperthermophilic T.
      tenax and homologs of mesophilic organisms establishes several characteristics of
      thermostabilization. These include protection against heat-induced covalent
      modifications by reducing and stabilizing labile residues, a decrease in number
      and volume of empty cavities, an increase in beta-strand content, and a
      strengthening of subunit contacts by ionic and hydrophobic interactions.

PMID- 11842091
TI  - Blood group A glycosyltransferase occurring as alleles with high sequence
      difference is transiently induced during a Nippostrongylus brasiliensis parasite
      infection.
AB  - Neutral mucin oligosaccharides from the small intestine of control rats and rats
      infected with the parasite Nippostrongylus brasiliensis were released and
      analyzed by gas chromatography-mass spectrometry. Infected animals expressed
      seven blood group A-like structures that were all absent in the control animals.
      The blood group A nature of these epitopes was confirmed by blood group A
      reactivity of the prepared mucins, of which Muc2 was one. Transferase assays and
      Northern blotting on small intestines from infected animals showed that an alpha
      N-acetylgalactosaminyltransferase similar to the human blood group A
      glycosyltransferase had been induced. The expression was a transient event, with
      a maximum at day 6 of the 13-day-long infection. The rat blood group A
      glycosyltransferase was cloned, revealing two forms with an amino acid similarity
      of 95%. Both types had blood group A transferase activity and were probably
      allelic because none of 12 analyzed inbred strains carried both types. The second
      type was found in outbred rats and in one inbred strain. First generation
      offspring of inbred rats of each type were heterozygous, further supporting the
      allelic hypothesis. The transient induction and the large allelic variation could
      suggest that glycosyltransferases are part of a dynamic system altering mucins
      and other glycoconjugates as a protecting mechanism against microbial challenges.

PMID- 11842092
TI  - Scheduled conversion of replication complex architecture at replication origins
      of Saccharomyces cerevisiae during the cell cycle.
AB  - Replication of DNA within Saccharomyces cerevisiae chromosomes is initiated from
      multiple origins, whose activation follow their own inherent time schedules
      during the S phase of the cell cycle. It has been demonstrated that a
      characteristic replicative complex (RC) that includes an origin recognition
      complex is formed at each origin and shifts between post- and pre-replicative
      states during the cell cycle. We wanted to determine whether there was an
      association between this shift in the state of the RC and firing events at
      replication origins. Time course analyses of RC architecture using UV
      footprinting with synchronously growing cells revealed that pre-replicative
      states at both early and late firing origins appeared simultaneously during late
      M phase, remained in this state during G(1) phase, and converted to the post
      replicative state at various times during S phase. Because the conversion of the
      origin footprinting profiles and origin firing, as assessed by two-dimensional
      gel electrophoresis, occurred concomitantly at each origin, then these two events
      must be closely related. However, conversion of the late firing origin occurred
      without actual firing. This was observed when the late origin was suppressed in
      clb5-deficient cells and a replication fork originating from an outside origin
      replicated the late origin passively. This mechanism ensures that replication at
      each chromosomal locus occurs only once per cell cycle by shifting existing pre
      RCs to the post-RC state, when it is replicated without firing.

PMID- 11842093
TI  - Calsarcin-3, a novel skeletal muscle-specific member of the calsarcin family,
      interacts with multiple Z-disc proteins.
AB  - The Z-disc is a highly specialized multiprotein complex of striated muscles that
      serves as the interface of the sarcomere and the cytoskeleton. In addition to its
      role in muscle contraction, its juxtaposition to the plasma membrane suggests
      additional functions of the Z-disc in sensing and transmitting external and
      internal signals. Recently, we described two novel striated muscle-specific
      proteins, calsarcin-1 and calsarcin-2, that bind alpha-actinin on the Z-disc and
      serve as intracellular binding proteins for calcineurin, a calcium/calmodulin
      dependent phosphatase shown to be integral in cardiac hypertrophy as well as
      skeletal muscle differentiation and fiber-type specification. Here, we describe
      an additional member of the calsarcin family, calsarcin-3, which is expressed
      specifically in skeletal muscle and is enriched in fast-twitch muscle fibers.
      Like calsarcin-1 and calsarcin-2, calsarcin-3 interacts with calcineurin, and the
      Z-disc proteins alpha-actinin, gamma-filamin, and telethonin. In addition, we
      show that calsarcins interact with the PDZ-LIM domain protein ZASP/Cypher/Oracle,
      which also localizes to the Z-disc. Calsarcins represent a novel family of
      sarcomeric proteins that serve as focal points for the interactions of an array
      of proteins involved in Z-disc structure and signal transduction in striated
      muscle.

PMID- 11842094
TI  - Kinetic characterization of human glutamine-fructose-6-phosphate amidotransferase
      I: potent feedback inhibition by glucosamine 6-phosphate.
AB  - Glutamine-fructose-6-phosphate amidotransferase (GFAT) catalyzes the first
      committed step in the pathway for biosynthesis of hexosamines in mammals. A
      member of the N-terminal nucleophile class of amidotransferases, GFAT transfers
      the amino group from the L-glutamine amide to D-fructose 6-phosphate, producing
      glutamic acid and glucosamine 6-phosphate. The kinetic constants reported
      previously for mammalian GFAT implicate a relatively low affinity for the
      acceptor substrate, fructose 6-phosphate (Fru-6-P, K(m) 0.2-1 mm). Utilizing a
      new sensitive assay that measures the production of glucosamine 6-phosphate (GlcN
      6-P), purified recombinant human GFAT1 (hGFAT1) exhibited a K(m) for Fru-6-P of 7
      microm, and was highly sensitive to product inhibition by GlcN-6-P. In a second
      assay method that measures the stimulation of glutaminase activity, a K(d) of 2
      microm was measured for Fru-6-P binding to hGFAT1. Further, we report that the
      product, GlcN-6-P, is a potent competitive inhibitor for the Fru-6-P site, with a
      K(i) measured of 6 microm. Unlike other members of the amidotransferase family,
      where glutamate production is loosely coupled to amide transfer, we have
      demonstrated that hGFAT1 production of glutamate and GlcN-6-P are strictly
      coupled in the absence of inhibitors. Similar to other amidotransferases,
      competitive inhibitors that bind at the synthase site may inhibit the synthase
      activity without inhibiting the glutaminase activity at the hydrolase domain.
      GlcN-6-P, for example, inhibited the transfer reaction while fully activating the
      glutaminase activity at the hydrolase domain. Inhibition of hGFAT1 by the end
      product of the pathway, UDP-GlcNAc, was competitive with a K(i) of 4 microm.
      These data suggest that hGFAT1 is fully active at physiological levels of Fru-6-P
      and may be regulated by its product GlcN-6-P in addition to the pathway end
      product, UDP-GlcNAc.

PMID- 11842095
TI  - Activator of G-protein signaling 1 blocks GIRK channel activation by a G-protein
      coupled receptor: apparent disruption of receptor signaling complexes.
AB  - The Ras-related protein, activator of G-protein signaling 1 (AGS1) or Dexras1,
      interacts with G(i)/G(o)alpha and activates heterotrimeric G-protein signaling
      systems independent of a G-protein-coupled receptor (GPCR). As an initial
      approach to further define the cellular role of AGS1 in GPCR signaling, we
      determined the influence of AGS1 on the regulation of G(betagamma)-regulated
      inwardly rectifying K(+) channel (GIRK) current (I(ACh)) by M(2)-muscarinic
      receptor (M(2)-MR) in Xenopus oocytes. AGS1 expression inhibited receptor
      mediated current activation by >80%. Mutation of a key residue (G31V) within the
      G(1) domain involved in nucleotide binding for Ras-related proteins eliminated
      the action of AGS1. The inhibition of I(ACh) was not overcome by increasing
      concentrations of the muscarinic agonist acetylcholine but was progressively lost
      upon injection of increasing amounts of M(2)-MR cRNA. These data suggest that
      AGS1 may antagonize GPCR signaling by altering the pool of heterotrimeric G
      proteins available for receptor coupling and/or disruption of a preformed
      signaling complex. Such regulation would be of particular importance for those
      receptors that exist precoupled to heterotrimeric G-protein and for receptors
      operating within signaling complexes.

PMID- 11842097
TI  - Integration sites for genetic elements in prokaryotic tRNA and tmRNA genes:
      sublocation preference of integrase subfamilies.
AB  - Most classical integrases of prokaryotic genetic elements specify integration
      into tRNA or tmRNA genes. Sequences shared between element and host integration
      sites suggest that crossover can occur at any of three sublocations within a tRNA
      gene, two with flanking symmetry (anticodon-loop and T-loop tDNA) and the third
      at the asymmetric 3' end of the gene. Integrase phylogeny matches this
      classification: integrase subfamilies use exclusively either the symmetric
      sublocations or the asymmetric sublocation, although tRNA genes of several
      different aminoacylation identities may be used within any subfamily. These two
      familial sublocation preferences imply two modes by which new integration site
      usage evolves. The tmRNA gene has been adopted as an integration site in both
      modes, and its distinctive structure imposes some constraints on proposed
      evolutionary mechanisms.

PMID- 11842098
TI  - Crystal structure of the Bse634I restriction endonuclease: comparison of two
      enzymes recognizing the same DNA sequence.
AB  - Crystal structures of Type II restriction endonucleases demonstrate a conserved
      common core and active site residues but diverse structural elements involved in
      DNA sequence discrimination. Comparative structural analysis of restriction
      enzymes recognizing the same nucleotide sequence might therefore contribute to
      our understanding of the structural diversity of specificity determinants within
      restriction enzymes. We have solved the crystal structure of the Bacillus
      stearothermophilus restriction endonuclease Bse634I by the multiple isomorphous
      replacement technique to 2.17 A resolution. Bse634I is an isoschisomer of the
      Cfr10I restriction enzyme whose crystal structure has been reported previously.
      Comparative structural analysis of the first pair of isoschisomeric enzymes
      revealed conserved structural determinants of sequence recognition and catalysis.
      However, conformations of the N-terminal subdomains differed between
      Bse634I/Cfr10I, suggesting a rigid body movement that might couple DNA
      recognition and catalysis. Structural similarities extend to the quaternary
      structure level: crystal contacts suggest that Bse634I similarly to Cfr10I is
      arranged as a tetramer. Kinetic analysis reveals that Bse634I is able to interact
      simultaneously with two recognition sites supporting the tetrameric architecture
      of the protein. Thus, restriction enzymes Bse634I, Cfr10I and NgoMIV, recognizing
      overlapping nucleotide sequences, exhibit a conserved tetrameric architecture
      that is of functional importance.

PMID- 11842099
TI  - Interactions of regulated and deregulated forms of the sigma54 holoenzyme with
      heteroduplex promoter DNA.
AB  - The bacterial sigma54 RNA polymerase holoenzyme binds to promoters as a stable
      closed complex that is silent for transcription unless acted upon by an enhancer
      bound activator protein. Using DNA binding and transcription assays the ability
      of the enhancer-dependent sigma54 holoenzyme to interact with promoter DNA
      containing various regions of heteroduplex from -12 to -1 was assessed. Different
      DNA regions important for stabilising sigma54 holoenzyme-promoter interactions,
      destabilizing binding, limiting template utilisation in activator-dependent
      transcription and for stable binding of a deregulated form of the holoenzyme
      lacking sigma54 Region I were identified. It appears that homoduplex structures
      are required for early events in sigma54 holoenzyme promoter binding and that
      disruption of a repressive fork junction structure only modestly deregulates
      transcription. DNA opening from -5 to -1 appears important for stable engagement
      of the holoenzyme following activation. The regulatory Region I of sigma54 was
      shown to be involved in interactions with the sequences in the -5 to -1 area.

PMID- 11842100
TI  - The Schizosaccharomyces pombe mgU6-47 gene is required for 2'-O-methylation of U6
      snRNA at A41.
AB  - Through a computer search of DNA databases, we have identified the homologs of
      the mgU6-47 snoRNA gene from the yeast Schizosaccharomyces pombe, the fly
      Drosophila melanogaster and human. The three box C/D-containing snoRNA genes
      showed no significant similarity in their sequences except for an 11 nt long
      complementarity to U6 snRNA, suggesting that the mechanism of snoRNA guided snRNA
      methylation is conserved from mammals to yeast. The corresponding snoRNAs have
      been positively detected by reverse transcription and northern blotting. Taking
      advantage of the fission yeast system, we have disrupted the yeast mgU6-47 gene
      and demonstrated that it is absolutely required for site-specific 2'-O
      methylation of U6 at position A41. No growth differences between mgU6-47 gene
      disrupted and wild-type cells were observed, suggesting that the mgU6-47 gene, as
      for most rRNA methylation guides, is dispensable in yeast. Nevertheless, it was
      revealed by temperature shift assay that abolition of A41 methylation in yeast U6
      snRNA might cause a small decrease in mRNA splicing efficiency. The timing of
      S.pombe U6 pre-RNA transport in the nucleus for splicing and methylation was also
      analyzed and is described.

PMID- 11842101
TI  - Role of nucleotidyltransferase motifs I, III and IV in the catalysis of
      phosphodiester bond formation by Chlorella virus DNA ligase.
AB  - ATP-dependent DNA ligases catalyze the sealing of 5'-phosphate and 3'-hydroxyl
      termini at DNA nicks by means of a series of three nucleotidyl transfer steps.
      Here we have analyzed by site-directed mutagenesis the roles of conserved amino
      acids of Chlorella virus DNA ligase during the third step of the ligation
      pathway, which entails reaction of the 3'-OH of the nick with the DNA-adenylate
      intermediate to form a phosphodiester and release AMP. We found that Asp65 and
      Glu67 in nucleotidyltransferase motif III and Glu161 in motif IV enhance the rate
      of step 3 phosphodiester formation by factors of 20, 1000 and 60, respectively.
      Asp29 and Arg32 in nucleotidyltransferase motif I enhance the rate of step 3 by
      60-fold. Gel shift analysis showed that mutations of Arg32 and Asp65 suppressed
      ligase binding to a pre-adenylated nick, whereas Asp29, Glu67 and Glu161 mutants
      bound stably to DNA-adenylate. We infer that Asp29, Glu67 and Glu161 are involved
      directly in the step 3 reaction. In several cases, the effects of alanine or
      conservative mutations on step 3 were modest compared to their effects on the
      composite ligation reaction and individual upstream steps. These results, in
      concert with available crystallographic data, suggest that the active site of DNA
      ligase is remodeled during the three steps of the pathway and that some of the
      catalytic side chains play distinct roles at different stages.

PMID- 11842102
TI  - Analysis of the structure of human telomerase RNA in vivo.
AB  - Telomerase is a ribonucleoprotein reverse transcriptase that synthesises
      telomeric DNA. The RNA component of telomerase acts as a template for telomere
      synthesis and binds the reverse transcriptase. In this study, we have performed
      in vivo and in vitro structural analyses of human telomerase RNA (hTR). In vivo
      mapping experiments showed that the 5'-terminal template domain of hTR folds into
      a long hairpin structure, in which the template sequence occupies a readily
      accessible position. Intriguingly, neither in vivo nor in vitro mapping of hTR
      confirmed formation of a stable 'pseudoknot' helix, suggesting that this
      functionally essential long range interaction is formed only temporarily. In
      vitro control mappings demonstrated that the 5'-terminal template domain of hTR
      cannot fold correctly in the absence of cellular protein factors. The 3'-terminal
      domain of hTR, both in vivo and in vitro, folds into the previously predicted box
      H/ACA snoRNA-like 'hairpin-hinge-hairpin-tail' structure. Finally, comparison of
      the in vivo and in vitro modification patterns of hTR revealed several regions
      that might be directly involved in binding of telomerase reverse transcriptase or
      other telomerase proteins.

PMID- 11842096
TI  - Natural and pharmacological regulation of telomerase.
AB  - The extremities of eukaryotic chromosomes are called telomeres. They have a
      structure unlike the bulk of the chromosome, which allows the cell DNA repair
      machinery to distinguish them from 'broken' DNA ends. But these specialised
      structures present a problem when it comes to replicating the DNA. Indeed,
      telomeric DNA progressively erodes with each round of cell division in cells that
      do not express telomerase, a specialised reverse transcriptase necessary to fully
      duplicate the telomeric DNA. Telomerase is expressed in tumour cells but not in
      most somatic cells and thus telomeres and telomerase may be proposed as
      attractive targets for the discovery of new anticancer agents.

PMID- 11842103
TI  - RNomics in Archaea reveals a further link between splicing of archaeal introns
      and rRNA processing.
AB  - The bulge-helix-bulge (BHB) motif recognised by the archaeal splicing
      endonuclease is also found in the long processing stems of archaeal rRNA
      precursors in which it is cleaved to generate pre-16S and pre-23S rRNAs. We show
      that in two species, Archaeoglobus fulgidus and Sulfolobus solfataricus,
      representatives from the two major archaeal kingdoms Euryarchaeota and
      Crenarchaeota, respectively, the pre-rRNA spacers cleaved at the BHB motifs
      surrounding pre-16S and pre-23S rRNAs subsequently become ligated. In addition,
      we present evidence that this is accompanied by circularization of ribosomal pre
      16S and pre-23S rRNAs in both species. These data reveal a further link between
      intron splicing and pre-rRNA processing in Archaea, which might reflect a common
      evolutionary origin of the two processes. One spliced RNA species designated 16S
      D RNA, resulting from religation at the BHB motif of 16S pre-rRNA, is a highly
      abundant and stable RNA which folds into a three-stem structure interrupted by
      two single-stranded regions as assessed by chemical probing. It spans a region of
      the pre-rRNA 5' external transcribed spacer exhibiting a highly conserved folding
      pattern in Archaea. Surprisingly, 16S-D RNA contains structural motifs found in
      archaeal C/D box small RNAs and binds to the L7Ae protein, a core component of
      archaeal C/D box RNPs. This supports the notion that it might have an important
      but still unknown role in pre-rRNA biogenesis or might even target RNA molecules
      other than rRNA.

PMID- 11842104
TI  - Archaeal ribosomal protein L7 is a functional homolog of the eukaryotic
      15.5kD/Snu13p snoRNP core protein.
AB  - Recent investigations have identified homologs of eukaryotic box C/D small
      nucleolar RNAs (snoRNAs) in Archaea termed sRNAs. Archaeal homologs of the box
      C/D snoRNP core proteins fibrillarin and Nop56/58 have also been identified but a
      homolog for the eukaryotic 15.5kD snoRNP protein has not been described. Our
      sequence analysis of archaeal genomes reveals that the highly conserved ribosomal
      protein L7 exhibits extensive homology with the eukaryotic 15.5kD protein.
      Protein binding studies demonstrate that recombinant Methanoccocus jannaschii L7
      protein binds the box C/D snoRNA core motif with the same specificity and
      affinity as the eukaryotic 15.5kD protein. Identical to the eukaryotic 15.5kD
      core protein, archaeal L7 requires a correctly folded box C/D core motif and
      intact boxes C and D. Mutational analysis demonstrates that critical features of
      the box C/D core motif essential for 15.5kD binding are also required for L7
      interaction. These include stem I which juxtaposes boxes C and D, as well as the
      sheared G:A pairs and protruded pyrimidine nucleotide of the asymmetric bulge
      region. The demonstrated presence of L7Ae in the Haloarcula marismortui 50S
      ribosomal subunit, taken with our demonstration of the ability of L7 to bind to
      the box C/D snoRNA core motif, indicates that this protein serves a dual role in
      Archaea. L7 functioning as both an sRNP core protein and a ribosomal protein
      could potentially regulate and coordinate sRNP assembly with ribosome biogenesis.

PMID- 11842106
TI  - Non-Watson-Crick interactions between PNA and DNA inhibit the ATPase activity of
      bacteriophage T4 Dda helicase.
AB  - Peptide nucleic acid (PNA) is a DNA mimic in which the nucleobases are linked by
      an N-(2-aminoethyl) glycine backbone. Here we report that PNA can interact with
      single-stranded DNA (ssDNA) in a non-sequence-specific fashion. We observed that
      a 15mer PNA inhibited the ssDNA-stimulated ATPase activity of a bacteriophage T4
      helicase, Dda. Surprisingly, when a fluorescein-labeled 15mer PNA was used in
      binding studies no interaction was observed between PNA and Dda. However,
      fluorescence polarization did reveal non-sequence-specific interactions between
      PNA and ssDNA. Thus, the inhibition of ATPase activity of Dda appears to result
      from depletion of the available ssDNA due to non-Watson-Crick binding of PNA to
      ssDNA. Inhibition of the ssDNA-stimulated ATPase activity was observed for
      several PNAs of varying length and sequence. To study the basis for this
      phenomenon, we examined self-aggregation by PNAs. The 15mer PNA readily self
      aggregates to the point of precipitation. Since PNAs are hydrophobic, they
      aggregate more than DNA or RNA, making the study of this phenomenon essential for
      understanding the properties of PNA. Non-sequence-specific interactions between
      PNA and ssDNA were observed at moderate concentrations of PNA, suggesting that
      such interactions should be considered for antisense and antigene applications.

PMID- 11842105
TI  - Molecular interactions of human Exo1 with DNA.
AB  - Human Exo1 is a member of the RAD2 nuclease family with roles in replication,
      repair and recombination. Despite sharing significant amino acid sequence
      homology, the RAD2 proteins exhibit disparate nuclease properties and biological
      functions. In order to identify elements that dictate substrate selectivity
      within the RAD2 family, we sought to identify residues key to Exo1 nuclease
      activity and to characterize the molecular details of the human Exo1-DNA
      interaction. Site-specific mutagenesis studies demonstrate that amino acids D78,
      D173 and D225 are critical for Exo1 nuclease function. In addition, we show that
      the chemical nature of the 5'-terminus has a major impact on Exo1 nuclease
      efficiency, with a 5'-phosphate group stimulating degradation 10-fold and a 5'
      biotin inhibiting degradation 10-fold (relative to a 5'-hydroxyl moiety). An
      abasic lesion located within a substrate DNA strand impedes Exo1 nucleolytic
      degradation, and a 5'-terminal abasic residue reduces nuclease efficiency 2-fold.
      Hydroxyl radical footprinting indicates that Exo1 binds predominantly along the
      minor groove of flap DNA, downstream of the junction. As will be discussed, our
      results favor the notion that the single-stranded DNA structure is pinched by the
      helical arch of the protein and not threaded through this key recognition loop.
      Furthermore, our studies indicate that significant, presumably biologically
      relevant, differences exist between the active site dynamics of Exo1 and Fen1.

PMID- 11842107
TI  - The MT domain of the proto-oncoprotein MLL binds to CpG-containing DNA and
      discriminates against methylation.
AB  - Alterations of the proto-oncogene MLL (mixed lineage leukemia) are characteristic
      for a high proportion of acute leukemias, especially those occurring in infants.
      The activation of MLL is achieved either by an internal tandem duplication of 5'
      MLL exons or by chromosomal translocations that create chimeric proteins with the
      N-terminus of MLL fused to a variety of different partner proteins. A domain of
      MLL with significant homology to the eukaryotic DNA methyltransferases (MT
      domain) has been found to be essential for the transforming potential of the
      oncogenic MLL derivatives. Here we demonstrate that this domain specifically
      recognizes DNA with unmethylated CpG sequences. In gel mobility shifts, the
      presence of CpG was sufficient for binding of recombinant GST-MT protein to DNA.
      The introduction of 5-methylCpG on one or both DNA strands precluded an efficient
      interaction. In surface plasmon resonance a KD of approximately 3.3 x 10(-8) M
      was determined for the GST-MT/DNA complex formation. Site selection experiments
      and DNase I footprinting confirmed CpG as the target of the MT domain. Finally,
      this interaction was corroborated in vivo in reporter assays utilizing the DNA
      binding properties of the MT domain in a hybrid MT-VP16 transactivator construct.

PMID- 11842108
TI  - A functional interaction between the putative primosomal protein DnaI and the
      main replicative DNA helicase DnaB in Bacillus.
AB  - In Gram negative Escherichia coli there are two well-characterised primosomal
      assembly processes, the PriA- and DnaA-mediated cascades. The presence of PriA
      and DnaA proteins in Gram positive Bacillus spp. supports the assumption that
      both the PriA- and DnaA-mediated primosomal assembly cascades also operate in
      these organisms. However, the lack of sequence homology between the rest of the
      primosomal proteins indicates significant differences between these two bacterial
      species. Central to the process of primosomal assembly is the loading of the main
      hexameric replicative helicase (DnaB in E.coli and DnaC in Bacillus subtilis) on
      the DNA. This loading is achieved by specialised proteins known as 'helicase
      loaders'. In E.coli DnaT and DnaC are responsible for loading DnaB onto the DNA
      during primosome assembly, in the PriA- and DnaA-mediated cascades, respectively.
      In Bacillus the identity of the helicase loader is still not established
      unequivocally. In this paper we provide evidence for a functional interaction
      between the primosomal protein DnaI from B.subtilis and the main hexameric
      replicative helicase DnaB from Bacillus stearothermophilus. Our results are
      consistent with the putative role of DnaI as the 'helicase loader' in the Gram
      positive Bacillus spp.

PMID- 11842110
TI  - Complete disproportionation of duplex poly(dT)*poly(dA) into triplex
      poly(dT)*poly(dA)*poly(dT) and poly(dA) by coralyne.
AB  - Coralyne is a small crescent-shaped molecule known to intercalate duplex and
      triplex DNA. We report that coralyne can cause the complete and irreversible
      disproportionation of duplex poly(dT)*poly(dA). That is, coralyne causes the
      strands of duplex poly(dT)*poly(dA) to repartition into equal molar equivalents
      of triplex poly(dT)*poly(dA)*poly(dT) and poly(dA). Poly(dT)*poly(dA) will remain
      as a duplex for months after the addition of coralyne, if the sample is
      maintained at 4 degrees C. However, disproportionation readily occurs upon
      heating above 35 degrees C and is not reversed by subsequent cooling. A titration
      of poly(dT)*poly(dA) with coralyne reveals that disproportionation is favored by
      as little as one molar equivalent of coralyne per eight base pairs of initial
      duplex. We have also found that poly(dA) forms a self-structure in the presence
      of coralyne with a melting temperature of 47 degrees C, for the conditions of our
      study. This poly(dA) self-structure binds coralyne with an affinity that is
      comparable with that of triplex poly(dT)*poly(dA)*poly(dT). A Job plot analysis
      reveals that the maximum level of poly(dA) self-structure intercalation is 0.25
      coralyne molecules per adenine base. This conforms to the nearest neighbor
      exclusion principle for a poly(dA) duplex structure with A*A base pairs. We
      propose that duplex disproportionation by coralyne is promoted by both the
      triplex and the poly(dA) self-structure having binding constants for coralyne
      that are greater than that of duplex poly(dT)*poly(dA).

PMID- 11842109
TI  - c-Maf, the gammaD-crystallin Maf-responsive element and growth factor regulation.
AB  - The transcription factor c-Maf has been suggested to regulate the activity of
      gamma-crystallin promoters in lens fibre cells. We here show that the
      transactivation potential of c-Maf and MafB for the rat gammaD-crystallin Maf
      responsive element (gammaD MARE) is dependent upon the cellular context and,
      using chimeric and single domain mutants, that c-Maf is most likely to be the
      cognate factor for the gammaD MARE in the lens. Transactivation of the gammaD
      MARE by c-Maf in lens cells was not enhanced by c-Fos or c-Jun and was not
      blocked by dominant negative c-Fos or c-Jun constructs. c-Maf can activate the
      gammaD MARE as a homodimer since activation of the gammaD-crystallin promoter in
      P19 embryonic carcinoma cells required only c-Maf, but none of a number of c-Fos
      and c-Jun family members tested. Transactivation by c-Maf was inhibited by
      activation of protein kinase A (PKA) (by signal transduction agonist forskolin)
      or of protein kinase C (PKC) (by signal transduction agonist tetradecanoyl
      phorbol acetate). Site-directed mutagenesis showed that this effect is not
      mediated by phosphorylation of the consensus PKA/PKC site in the extended DNA
      binding domain, but likely involves activation of MAP kinase kinase, as
      inhibition by PD98059 increased transactivation by c-Maf.

PMID- 11842111
TI  - Complex regulation of the human gene for the Z-DNA binding protein DLM-1.
AB  - Dlm-1 is a recently described gene which is upregulated in murine stromal cells
      lining tumors. The function of the 40 kDa DLM-1 protein is poorly understood. DLM
      1 contains an N-terminal Z-DNA binding domain homologous to the Zalpha domain in
      the RNA editing enzyme ADAR1. We report the cloning of human and rat DLM-1. In
      addition to the Zalpha domain, three further conserved regions were identified.
      One of these is homologous to the second Z-DNA binding domain, Zbeta, of ADAR1.
      We find that human DLM-1 is predominantly expressed in lymphatic tissues. The
      gene spans 17 kb and consists of 10 exons. DNA transcripts are extremely
      heterogeneous as a result of alternative splicing and the usage of exon variants
      combined with at least two transcriptional start sites and 3'-terminal exons. The
      exon coding for the Zalpha domain was present in approximately one-third of the
      analyzed mRNAs. Nearly half of the transcripts contained exon variants that had
      premature stop codons incorporated. Based on our analysis, over 2000 different
      mRNAs may be produced due to alternative splicing and usage of different 5' and
      3' ends. The cellular function of DLM-1 appears to call for a high degree of
      adaptation by this complex regulation.

PMID- 11842113
TI  - Involvement of Rad51C in two distinct protein complexes of Rad51 paralogs in
      human cells.
AB  - Genetic studies in rodent and chicken mutant cell lines have suggested that Rad51
      paralogs (XRCC2, XRCC3, Rad51B/Rad51L1, Rad51C/Rad51L2 and Rad51D/Rad51L3) play
      important roles in homologous recombinational repair of DNA double-strand breaks
      and in maintaining chromosome stability. Previous studies using yeast two- and
      three-hybrid systems have shown interactions among these proteins, but it is not
      clear whether these interactions occur simultaneously or sequentially in vivo. By
      utilizing immunoprecipitation with extracts of human cells expressing epitope
      tagged Rad51 paralogs, we demonstrate that XRCC2 and Rad51D, while stably
      interacting with each other, co-precipitate with Rad51C but not with XRCC3. In
      contrast, Rad51C is pulled down with XRCC3, whereas XRCC2 and Rad51D are not. In
      addition, Rad51B could be pulled down with Rad51C and Rad51D, but not with XRCC3.
      These results suggest that Rad51C is involved in two distinct in vivo complexes:
      Rad51B-Rad51C-Rad51D-XRCC2 and Rad51C-XRCC3. In addition, we demonstrate that
      Rad51 co-precipitates with XRCC3 but not with XRCC2 or Rad51D, suggesting that
      Rad51 can be present in an XRCC3-Rad51C-Rad51 complex. These complexes may act as
      functional units and serve accessory roles for Rad51 in the presynapsis stage of
      homologous recombinational repair.

PMID- 11842112
TI  - Interactions involving the Rad51 paralogs Rad51C and XRCC3 in human cells.
AB  - Homologous recombinational repair of DNA double-strand breaks and crosslinks in
      human cells is likely to require Rad51 and the five Rad51 paralogs (XRCC2, XRCC3,
      Rad51B/Rad51L1, Rad51C/Rad51L2 and Rad51D/Rad51L3), as has been shown in chicken
      and rodent cells. Previously, we reported on the interactions among these
      proteins using baculovirus and two- and three-hybrid yeast systems. To test for
      interactions involving XRCC3 and Rad51C, stable human cell lines have been
      isolated that express (His)6-tagged versions of XRCC3 or Rad51C. Ni2+-binding
      experiments demonstrate that XRCC3 and Rad51C interact in human cells. In
      addition, we find that Rad51C, but not XRCC3, interacts directly or indirectly
      with Rad51B, Rad51D and XRCC2. These results argue that there are at least two
      complexes of Rad51 paralogs in human cells (Rad51C-XRCC3 and Rad51B-Rad51C-Rad51D
      XRCC2), both containing Rad51C. Moreover, Rad51 is not found in these complexes.
      X-ray treatment did not alter either the level of any Rad51 paralog or the
      observed interactions between paralogs. However, the endogenous level of Rad51C
      is moderately elevated in the XRCC3-overexpressing cell line, suggesting that
      dimerization between these proteins might help stabilize Rad51C.

PMID- 11842114
TI  - Correlating protein footprinting with mutational analysis in the bacterial
      transcription factor sigma54 (sigmaN).
AB  - Protein footprints of the enhancer-dependent sigma54 protein, upon binding the
      Escherichia coli RNA polymerase core enzyme or upon forming closed promoter
      complexes, identified surface-exposed residues in sigma54 of potential functional
      importance at the interface between sigma54 and core RNA polymerases (RNAP) or
      DNA. We have now characterised alanine and glycine substitution mutants at
      several of these positions. Properties of the mutant sigma54s correlate protein
      footprints to activity. Some mutants show elevated DNA binding suggesting that
      promoter binding by holoenzyme may be limited to enable normal functioning. One
      such mutant (F318A) within the DNA binding domain of sigma54 shows a changed
      interaction with the promoter regulatory region implicated in transcription
      silencing and fails to silence transcription in vitro. It appears specifically
      defective in preferentially binding to a repressive DNA structure believed to
      restrict RNA polymerase isomerisation and is largely intact for activator
      responsiveness. Two mutants, one in the regulatory region I and the other within
      core interacting sequences of sigma54, failed to stably bind the activator in the
      presence of ADP-aluminium fluoride, an analogue of ATP in the transition state
      for hydrolysis. Overall, the data presented describe a collection sigma54 mutants
      that have escaped previous analysis and display an array of properties which
      allows the role of surface-exposed residues in the regulation of open complex
      formation and promoter DNA binding to be better understood. Their properties
      support the view that the interface between sigma54 and core RNAP is functionally
      specialised.

PMID- 11842115
TI  - Functional and physical interactions between components of the Prp19p-associated
      complex.
AB  - The Prp19p-associated complex is essential for the yeast pre-mRNA splicing
      reaction. The complex consists of at least eight protein components, but is not
      tightly associated with spliceosomal snRNAs. By a combination of genetic and
      biochemical methods we previously identified four components of this complex,
      Ntc25p, Ntc85p, Ntc30p and Ntc20p, all of them being novel splicing factors. We
      have now identified three other components of the complex, Ntc90p, Ntc77p and
      Ntc31p. These three proteins were also associated with the spliceosome during the
      splicing reaction in the same manner as Prp19p, concurrently with or immediately
      after dissociation of U4 snRNA. Two-hybrid analysis revealed that none of these
      proteins interacted with Prp19p or Ntc25p, but all interacted with Ntc85p. An
      interaction network between the identified components of the Prp19p-associated
      complex is demonstrated. Biochemical analysis revealed that Ntc90p, Ntc31p,
      Ntc30p and Ntc20p form a subcomplex, which, through interacting with Ntc85p and
      Ntc77p, can associate with Prp19p and Ntc25p to form the Prp19p-associated
      complex. Genetic analysis suggests that Ntc31p, Ntc30p and Ntc20p may play roles
      in modulating the function of Ntc90p.

PMID- 11842116
TI  - Neuroendocrine differentiation factor, IA-1, is a transcriptional repressor and
      contains a specific DNA-binding domain: identification of consensus IA-1 binding
      sequence.
AB  - A novel cDNA, insulinoma-associated antigen-1 (IA-1), containing five zinc-finger
      DNA-binding motifs, was isolated from a human insulinoma subtraction library. IA
      1 expression is restricted to fetal but not adult pancreatic and brain tissues as
      well as tumors of neuroendocrine origin. Using various GAL4 DNA binding domain
      (DBD)/IA-1 fusion protein constructs, we demonstrated that IA-1 functions as a
      transcriptional repressor and that the region between amino acids 168 and 263
      contains the majority of the repressor activity. Using a selected and amplified
      random oligonucleotide binding assay and bacterially expressed GST-IA-1DBD fusion
      protein (257-510 a.a.), we identified the consensus IA-1 binding sequence,
      TG/TC/TC/TT/AGGGGG/TCG/A. Further experiments showed that zinc-fingers 2 and 3 of
      IA-1 are sufficient to demonstrate transcriptional activity using an IA-1
      consensus site containing a reporter construct. A database search with the
      consensus IA-1 binding sequence revealed target sites in a number of pancreas-
      and brain-specific genes consistent with its restricted expression pattern. The
      most significant matches were for the 5'-flanking regions of IA-1 and
      NeuroD/beta2 genes. Co-transfection of cells with either the full-length IA-1 or
      hEgr-1AD/IA-1DBD construct and IA-1 or NeuroD/beta2 promoter/CAT construct
      modulated CAT activity. These findings suggest that the IA-1 protein may be auto
      regulated and play a role in pancreas and neuronal development, specifically in
      the regulation of the NeuroD/beta2 gene.

PMID- 11842117
TI  - Functional dissection of the ParB homologue (KorB) from IncP-1 plasmid RK2.
AB  - Active partitioning of low-copy number plasmids requires two proteins belonging
      to the ParA and ParB families and a cis-acting site which ParB acts upon. Active
      separation of clusters of plasmid molecules to the defined locations in the cell
      before cell division ensures stable inheritance of the plasmids. The central
      control operon of IncP-1 plasmids codes for regulatory proteins involved in the
      global transcriptional control of operons for vegetative replication, stable
      maintenance and conjugative transfer. Two of these proteins, IncC and KorB, also
      play a role in active partitioning, as the ParA and ParB homologues,
      respectively. Here we describe mapping the regions in KorB responsible for four
      of its different functions: dimerisation, DNA binding, repression of
      transcription and interaction with IncC. For DNA binding, amino acids E151 to
      T218 are essential, while repression depends not only on DNA binding but,
      additionally, on the adjacent region amino acids T218 to R255. The C-terminus of
      KorB is the main dimerisation domain but a secondary oligomerisation region is
      located centrally in the region from amino acid I174 to T218. Using three
      different methods (potentiation of transcriptional repression, potentiation of
      DNA binding and activation in the yeast two-hybrid system) we identify this
      region as also responsible for interactions with IncC. This IncC-KorB contact
      differs in location from the ParA-ParB/SopA-SopB interactions in P1/F but is
      similar to these systems in lying close to a masked oligomerisation determinant.

PMID- 11842118
TI  - GATA-4 interacts distinctively with negative and positive regulatory elements in
      the Fgf-3 promoter.
AB  - GATA-4 binds two sites in the Fgf-3 promoter, PS4A and PS13, which function as
      positive and negative regulatory elements, respectively. In spite of their
      opposite functions, both PS4A and PS13 acted as potent enhancer elements when
      three copies of each were appended to a minimal tk promoter. Mutational analysis
      showed that the negative regulatory activity of PS13 was dependent on its close
      proximity to the major transcription initiation site (P3), since it was a
      stronger repressor when moved closer to P3, but had no significant activity when
      moved to more distal positions. While only the C-terminal zinc finger and the
      basic domain of GATA-4 were required for binding to PS13, this was insufficient
      for binding at PS4A. In addition to the PS4A GATA site, the presence of sequences
      located 10-12 bp distant was required for efficient binding. Both the sequence
      and location of this second site was crucial for binding and enhancer activity.
      Truncation deletions of GATA-4 showed that efficient binding to PS4A was
      dependent on both zinc fingers and the basic domain, suggesting a direct
      interaction between one zinc finger domain and a possible second site (AGACAA)
      that shows some similarity to a GATA motif. GATA-4 binding to PS4A through both
      zinc finger domains was essential for Fgf-3 promoter activity. The substitution
      in PS4A of a GATA-binding sequence similar to PS13, which only requires a single
      zinc finger domain, bound GATA-4 efficiently but did not activate the Fgf-3
      promoter. These differences in GATA-4 binding were also reflected in DNA bending
      assays that suggested clear conformational differences between complexes formed
      on PS4A and PS13.

PMID- 11842119
TI  - In vitro structure-function studies of the Bacillus subtilis tyrS mRNA
      antiterminator: evidence for factor-independent tRNA acceptor stem binding
      specificity.
AB  - Expression of many aminoacyl-tRNA synthetase, amino acid biosynthesis and
      transport genes in Bacillus subtilis is controlled at the level of transcription
      termination using the T box system and requires the formation of specific
      secondary structures in the mRNA leader region. One structure functions as a
      transcriptional terminator, while an alternate form, the antiterminator, is
      necessary for transcription of the downstream coding regions. We have
      investigated the interaction of antiterminator model RNAs, based on the
      B.subtilis tyrS antiterminator with tRNA(Tyr) and tRNA acceptor stem models,
      using a gel shift assay. Binding of the antiterminator RNA to tRNA(Tyr) was
      dependent on complimentarity with the acceptor end of the tRNA or microhelix;
      affinity for the microhelix RNA was reduced relative to the tRNA. Alteration of a
      conserved position in the non-base pairing region of the bulge greatly reduced
      tRNA binding, consistent with in vivo studies. Therefore, it appears that some of
      the antiterminator-tRNA binding specificity is dependent on the structure of the
      antiterminator bulge alone and the complex it forms with tRNA in the absence of
      additional trans-acting factors. During the course of these studies we also
      discovered that the antiterminator can form a 'kissing' bulge complex, a unique
      RNA motif. The ease of formation of this RNA homodimer illustrates the propensity
      for the bulge of the antiterminator to bind RNA.

PMID- 11842120
TI  - Mutational analysis defines the 5'-kinase and 3'-phosphatase active sites of T4
      polynucleotide kinase.
AB  - T4 polynucleotide kinase (Pnk) is a bifunctional 5'-kinase/3'-phosphatase that
      aids in the repair of broken termini in RNA by converting 3'-PO4/5'-OH ends into
      3'-OH/5'-PO4 ends, which are then sealed by RNA ligase. Here we have employed
      site-directed mutagenesis (introducing 31 mutations at 16 positions) to locate
      candidate catalytic residues within the 301 amino acid Pnk polypeptide. We found
      that alanine substitutions for Arg38 and Arg126 inactivated the 5'-kinase, but
      spared the 3'-phosphatase activity. Conservative substitutions of lysine or
      glutamine for Arg38 and Arg126 did not restore 5'-kinase activity. These results,
      together with previous mutational studies, highlight a constellation of five
      amino acids (Lys15, Ser16, Asp35, Arg38 and Arg126) that likely comprise the 5'
      kinase active site. Four of these residues are conserved at the active sites of
      adenylate kinases (Adk), suggesting that Pnk and Adk are structurally and
      mechanistically related. We found that alanine substitutions for Asp165, Asp167,
      Arg176, Arg213, Asp254 and Asp278 inactivated the 3'-phosphatase, but spared the
      5'-kinase. Conservative substitutions of asparagine or glutamate for Asp165,
      Asp167 and Asp254 did not revive the 3'-phosphatase activity, nor did lysine
      substitutions for Arg176 and Arg213. Glutamate in lieu of Asp278 partially
      restored activity, whereas asparagine had no salutary effect. Alanine
      substitutions for Arg246 and Arg279 partially inactivated the 3'-phosphatase; the
      conservative R246K change restored activity, whereas R279K had no benefit. The
      essential phosphatase residues Asp165 and Asp167 are located within a 165DxDxT169
      motif that defines a superfamily of phosphotransferases. Our data suggest that
      the 3'-phosphatase active site incorporates multiple additional functional
      groups.

PMID- 11842121
TI  - Normalization for cDNA microarray data: a robust composite method addressing
      single and multiple slide systematic variation.
AB  - There are many sources of systematic variation in cDNA microarray experiments
      which affect the measured gene expression levels (e.g. differences in labeling
      efficiency between the two fluorescent dyes). The term normalization refers to
      the process of removing such variation. A constant adjustment is often used to
      force the distribution of the intensity log ratios to have a median of zero for
      each slide. However, such global normalization approaches are not adequate in
      situations where dye biases can depend on spot overall intensity and/or spatial
      location within the array. This article proposes normalization methods that are
      based on robust local regression and account for intensity and spatial dependence
      in dye biases for different types of cDNA microarray experiments. The selection
      of appropriate controls for normalization is discussed and a novel set of
      controls (microarray sample pool, MSP) is introduced to aid in intensity
      dependent normalization. Lastly, to allow for comparisons of expression levels
      across slides, a robust method based on maximum likelihood estimation is proposed
      to adjust for scale differences among slides.

PMID- 11842122
TI  - Enzymatic repair of selected cross-linked homoduplex molecules enhances nuclear
      gene rescue from Pompeii and Herculaneum remains.
AB  - Ancient DNA (aDNA) samples extracted from the bone remains of six equids buried
      by the Vesuvius eruption in 79 AD were investigated to test pre-amplification and
      enzymatic repair procedures designed to enhance the rescue of nuclear genes. The
      extracts, which proved all positive for Equidae mtDNA amplification, proved
      positive only four times out of 18 when tested for single-copy Equidae nuclear
      genes (epsilon globin, p53 and gamma interferon). Pre-amplification did not
      change the number of retrieved aDNA sequences but 10 times out of 14 enzymatic
      repair restored the amplifiability of the genes analysed, proving that repair
      increases the rate of successful rescue from 22 to
      alpha(lambda)mu(omicron)sigma(tau) 80%. These findings support the hypothesis
      that some of these cross-linked aDNA molecules, which are not completely
      separated when DNA is extracted under denaturing conditions, become homoduplex
      substrates for Pol I and/or T4 ligase action upon renaturation. aDNA authenticity
      is proved by the homology of the nucleotide sequences of loci tested to the
      corresponding modern Equidae sequences. Data also indicate that cross-linked
      homoduplex molecules selected by denaturation of the extract are repaired without
      any chimera formation. The general features of aDNA amplification with and
      without denaturation and enzymatic repair are discussed.

PMID- 11842123
TI  - A novel sensitive microarray approach for differential screening using probes
      labelled with two different radioelements.
AB  - We have developed a novel microarray approach for differential screening using
      probes labelled with two different radioelements. The complementary DNAs from the
      reverse transcription of mRNAs from two different biological samples were
      labelled with radioelements of significantly different energies (3H and 35S or
      33P). Radioactive images corresponding to the expressed genes were acquired with
      a MicroImager, a real time, high resolution digital autoradiography system. An
      algorithm was used to process the data such that the initially acquired
      radioactive image was filtered into two subimages, each representative of the
      hybridisation result specific for one probe. The simultaneous screening of gene
      expression in two different biological samples requires <100 ng mRNA without any
      amplification. In such conditions, the technique is sensitive enough to directly
      quantify the amount of mRNA even when present in small amounts: 10(7) molecules
      in the probe as assessed with an added control sequence and 2 x 10(5) molecules
      with an endogenous tyrosine hydroxylase mRNA. This novel technique of double
      radioactive labelling on a microarray is thus suitable for the comparison of gene
      expression in two different biological samples available in only small
      quantities. Consequently, it has great potential for various biological fields,
      such as neuroscience.

PMID- 11842124
TI  - Ethics, revisited.

PMID- 11842125
TI  - Settling down for a long winter's nap: focus on "coordinate expression of the
      PDK4 gene: a means of regulating fuel selection in a hibernating mammal".

PMID- 11842126
TI  - Coordinate expression of the PDK4 gene: a means of regulating fuel selection in a
      hibernating mammal.
AB  - Hibernation in mammals requires a metabolic shift away from the oxidation of
      carbohydrates and toward the combustion of stored fatty acids as the primary
      source of energy during torpor. A key element involved in this fuel selection is
      pyruvate dehydrogenase kinase isoenzyme 4 (PDK4). PDK4 inhibits pyruvate
      dehydrogenase and thus minimizes carbohydrate oxidation by preventing the flow of
      glycolytic products into the tricarboxylic acid cycle. This paper examines
      expression of the PDK4 gene during hibernation in heart, skeletal muscle, and
      white adipose tissue (WAT) of the 13-lined ground squirrel, Spermophilus
      tridecemlineatus. During hibernation PDK4 mRNA levels increase 5-fold in skeletal
      muscle and 15-fold in WAT compared with summer-active levels. Similarly, PDK4
      protein is increased threefold in heart, fivefold in skeletal muscle, and
      eightfold in WAT. High levels of serum insulin, likely to have an inhibitory
      effect on PDK4 gene expression, are seen during fall when PDK4 mRNA levels are
      low. Coordinate upregulation of PDK4 in three distinct tissues suggests a common
      signal that regulates PDK4 expression and fuel selection during hibernation.

PMID- 11842127
TI  - Chromosome 1 blood pressure QTL region influences renal function curve and salt
      sensitivity in SHR.
AB  - One or more quantitative trait locus (QTL) for blood pressure (BP) exists on rat
      chromosome 1, in the vicinity of the Sa gene. The present work examined whether
      this QTL region: 1) alters pressure-natriuresis relationship and 2) affects the
      BP response to salt load. Male spontaneously hypertensive rats (SHR), Wistar
      Kyoto (WKY) rats, and rats from an SHR congenic strain that contains a WKY
      chromosome 1 segment spanning the BP QTL region (SHR. WKY-Sa) were used. In an
      acute study in anesthetized animals, renal function was measured at several
      levels of renal perfusion pressure. In a chronic study, BP was measured in freely
      moving rats using telemetry during normal and high sodium intake (2% NaCl as
      drinking water for 2 wk). WKY rats showed a significantly higher glomerular
      filtration rate and increased pressure-natriuresis compared with SHR. SHR.WKY-Sa
      also demonstrated an increased glomerular filtration rate and enhanced pressure
      natriuresis, associated with a lower tubular sodium reabsorption, compared with
      SHR. These modifications were accompanied by a lower basal BP in SHR.WKY-Sa
      compared with SHR and a markedly reduced BP response to salt load. These findings
      suggest that the BP QTL(s) present in this region of chromosome 1 influences BP
      and salt sensitivity, at least partly, by modulating pressure-natriuresis.

PMID- 11842128
TI  - Gene expression profiles in human cardiac cells subjected to hypoxia or
      expressing a hybrid form of HIF-1 alpha.
AB  - The cellular response to hypoxia depends on rapid posttranslational modifications
      of proteins as well as regulation of gene expression. We performed serial
      analysis of gene expression (SAGE) on human cardiac cells under normoxia,
      subjected to hypoxia, or infected with Ad2/HIF-1alpha/VP16 (an adenoviral vector
      expressing a stable hybrid form of hypoxia-inducible factor 1alpha) or Ad2/CMVEV
      (an empty vector). Of the 97,646 SAGE tags that were sequenced, 27% matched
      GenBank entries, while an additional 32% matched expressed sequence tags (ESTs)
      in UniGene. We analyzed 161 characterized genes or ESTs with a putative
      identification. Expression of 35, 11, and 46 genes was increased by hypoxia,
      infection with Ad2/EVCMV, or infection with Ad2/HIF-1alpha/VP16, respectively,
      compared with normoxia; conversely, 20, 11, 38 genes, respectively, were
      expressed at lower levels. Genes regulated by hypoxia were associated with
      transcription, biosynthesis, extracellular matrix formation, glycolysis, energy
      production, cell survival, and cell stress. Changes following infection with
      Ad2/HIF-1alpha/VP16 mimicked the hypoxic response to a certain extent. Infection
      with Ad2/CMVEV affected expression of genes that were associated with
      extracellular matrix formation and membrane trafficking. Differential expression
      of select genes was confirmed using TaqMan in additional human cardiac cells and
      rat neonatal ventricular myocytes. These data provide insight into gene
      expression underlying the diverse and complex cellular response to hypoxia,
      expression of HIF-1alpha/VP16, or adenoviral infection.

PMID- 11842129
TI  - Integrating genomics technologies in health care: practice and policy challenges
      and opportunities.
AB  - To consider broadly the potential impacts of new genetic technologies on clinical
      practice, a conference was convened at the Banbury Center of the Cold Spring
      Harbor Laboratories. Stakeholders from all sectors (industry, academia, basic and
      applied research, clinical genetics, medicine, law, patient advocacy, bioethics,
      and policy and regulatory) were brought together to explore areas of agreement
      and disagreement on how best to foster these changes and to guide future
      deliberations. We first examined the current state of technology development and
      potential applications. Next, current genetic applications in medicine were
      reviewed with the goal of identifying lessons learned and practices that can be
      applied to new applications. Last, the group explored regulatory and policy
      environments necessary for translating new technologies and knowledge into
      practice. We sought to better define and facilitate the necessary interaction
      between research, application, and policy and regulation. This perspective
      provides a summary of the collective thinking that emerged and a tool to identify
      issues for consideration and aid future discussions.

PMID- 11842130
TI  - Cloning, tissue distribution, and functional expression of the human G protein
      beta 4-subunit.
AB  - Heterotrimeric G proteins (Galphabetagamma) play an essential role in coupling
      membrane receptors to effector proteins such as ion channels and enzymes. Among
      the five mammalian Gbeta-subunits cloned, the human G protein beta4 has not been
      described. The purpose of the present study was to functionally characterize the
      newly identified human Gbeta4 subunit. The Gbeta4 open reading frame (ORF) was
      amplified utilizing PCR from brain cDNA. Amplification primers were generated
      following 5' rapid amplification of cDNA ends (5'-RACE) from an expressed
      sequence tag (EST) containing the predicted 3' end of the protein. Multiple
      tissue cDNA panel analysis showed that Gbeta4 mRNA was strongly expressed in lung
      and placenta, whereas it is weakly expressed in brain and heart. Heterologous
      overexpression of Gbeta4gamma2 or Gbeta4gamma4 in rat sympathetic neurons
      resulted in tonic modulation of N-type voltage-gated Ca(2+) and G protein-gated
      inwardly rectifying K(+) currents. Furthermore, coexpression of Gbeta4gamma2 and
      Galpha(oA) resulted in heterotrimer formation. These results show that the newly
      cloned Gbeta subunit shares several properties with other human Gbeta family
      members.

PMID- 11842131
TI  - Zebrafish mitotic kinesin-like protein 1 (Mklp1) functions in embryonic
      cytokinesis.
AB  - To understand the functions of microtubule motors in vertebrate development, we
      are investigating the kinesin-like proteins (KLPs) of the zebrafish, Danio rerio.
      Here we describe the structure, intracellular distribution, and function of
      zebrafish mitotic KLP1 (Mklp1). The zebrafish mklp1 gene that encodes this 867
      amino acid protein maps to a region of zebrafish linkage group 18 that is
      syntenic with part of human chromosome 15. In zebrafish AB9 fibroblasts and in
      COS-7 cells, the zebrafish Mklp1 protein decorates spindle microtubules at
      metaphase, redistributes to the spindle midzone during anaphase, and becomes
      concentrated in the midbody during telophase and cytokinesis. The motor is
      detected consistently in interphase nuclei of COS cells and occasionally in those
      of AB9 cells. Nuclear targeting of Mklp1 is conferred by two basic motifs located
      in the COOH terminus of the motor. In cleaving zebrafish embryos, green
      fluorescent protein (GFP)-tagged Mklp1 is found in the nucleus in interphase and
      associates with microtubules of the spindle midbody in cytokinesis. One- or two
      cell embryos injected with synthetic mRNAs encoding dominant-negative variants of
      GFP-Mklp1 frequently fail to complete cytokinesis during cleavage, resulting in
      formation of multinucleated blastomeres. Our results indicate that the zebrafish
      Mklp1 motor performs a critical function that is required for completion of
      embryonic cytokinesis.

PMID- 11842132
TI  - Interacting QTLs for cholesterol gallstones and gallbladder mucin in AKR and SWR
      strains of mice.
AB  - We employed quantitative trait locus (QTL) mapping in a backcross between
      gallstone-susceptible SWR/J and gallstone-resistant AKR/J inbred mice to identify
      additional susceptibility loci for cholesterol gallstone formation. After 12 wk
      of feeding the mice a lithogenic diet, we phenotyped 330 backcross progeny for
      gallstones, gallbladder mucin accumulation, liver weight, and body weight. Marker
      based regression analysis revealed significant single QTLs associated with
      gallstone formation on chromosome 9 and the liver weight/body weight ratio on
      chromosomes 5 and X. A search for gene pairs detected significant gene-gene
      interactions for mucin accumulation between loci on chromosomes 5 and 11 and
      suggestive gene-gene interactions linked to gallstone formation between the QTL
      on chromosome 9 and loci on chromosomes 6 and 15. These findings uncover new QTLs
      for cholesterol gallstones, reveal independent loci for mucin accumulation, and
      demonstrate the importance of considering gene-gene interactions in cholesterol
      cholelithiasis. According to standard nomenclature, the gallstone QTL on
      chromosome 9 is named Lith5.

PMID- 11842136
TI  - Cellulose synthase-like genes of rice.

PMID- 11842137
TI  - When a day makes a difference. Interpreting data from endoplasmic reticulum
      targeted green fluorescent protein fusions in cells grown in suspension culture.

PMID- 11842138
TI  - The wall becomes surmountable.

PMID- 11842139
TI  - Cytokinins. New insights into a classic phytohormone.

PMID- 11842140
TI  - Plant two-component signaling systems and the role of response regulators.

PMID- 11842141
TI  - Voltage-dependent cation channels permeable to NH(+)(4), K(+), and Ca(2+) in the
      symbiosome membrane of the model legume Lotus japonicus.
AB  - The symbiosome of nitrogen fixing root nodules mediates metabolite exchange
      between endosymbiotic rhizobia bacteria and the legume host. In the present
      study, the ion currents of the symbiosome membrane of the model legume Lotus
      japonicus were analyzed by patch-clamp recording. Both excised and symbiosome
      attached patches exhibited a large inward (toward the cytosolic side of the
      membrane) current that is activated in a time-dependent manner by negative (on
      the cytosolic side) potentials. Based on reversal potential determinations and
      recordings with the impermeant cation N-methyl-glucamine, this current shows a
      high permeability for monovalent cations with no apparent permeability for
      anions. The current also showed a finite Ca(2+) permeability. However, the
      currents were predominantly carried by univalent cations with a slightly greater
      selectivity for NH(4)(+) over K(+). Increased Ca(2+) concentration inhibited the
      current with a K(0.5) for inhibition of 0.317 mM. The current showed strong
      rectification that is mediated by divalent cations (either Mg(2+) or Ca(2+)). The
      influence of divalent cations is symmetrical in nature, because rectification can
      be exerted in either direction depending upon which side of the membrane has the
      highest concentration of divalent cations. However, based on observations with
      symbiosome-attached patches, the direction of the current in vivo is proposed to
      be toward the cytosol with cytosolic Mg(2+) acting as the putative gating
      regulator. The findings suggest that L. japonicus possesses a voltage-dependent
      cation efflux channel that is capable of exporting fixed NH(4)(+), and may also
      play an additional role in Ca(2+) transport.

PMID- 11842142
TI  - Sodium fluxes through nonselective cation channels in the plasma membrane of
      protoplasts from Arabidopsis roots.
AB  - The aim of the present work was to characterize Na(+) currents through
      nonselective cation channels (NSCCs) in protoplasts derived from root cells of
      Arabidopsis. The procedure of the protoplast isolation was modified to increase
      the stability of Arabidopsis root protoplasts in low external Ca(2+) by digesting
      tissue in elevated Ca(2+). Experiments in whole-cell and outside-out modes were
      carried out. We found that Na(+) currents in Arabidopsis root protoplasts were
      mediated by cation channels that were insensitive to externally applied
      tetraethylammonium(+) and verapamil, had no time-dependent activation
      (permanently opened or completely activated within 1-2 ms), were voltage
      independent, and were weakly selective for monovalent cations. The selectivity
      sequence was as follows: K(+) (1.49) > NH(4)(+) (1.24) > Rb(+) (1.15)
      approximately equal to Cs(+) (1.10) approximately equal to Na(+) (1.00) > Li(+)
      (0.73) > tetraethylammonium(+) (0.47). Arabidopsis root NSCCs were blocked by
      H(+) (pK approximately equal to 6.0), Ca(2+) (K(1/2) approximately equal to 0.1
      mM), Ba(2+), Zn(2+), La(3+), Gd(3+), quinine, and the His modifier
      diethylpyrocarbonate. They were insensitive to most organic blockers (nifedipine,
      verapamil, flufenamate, and amiloride) and to the SH-group modifier p
      chloromercuriphenyl sulfonic acid. Voltage-insensitive, Ca(2+)-sensitive single
      channels were also resolved. Properties of Arabidopsis root NSCCs are discussed
      and compared with characteristics of similar conductances studied previously in
      plants and animals. It is suggested that NSCCs present a distinct group of plant
      ion channels, mediating toxic Na(+) influx to the cell and probably having other
      important roles in physiological processes of plants.

PMID- 11842143
TI  - Nonselective currents and channels in plasma membranes of protoplasts from coats
      of developing seeds of bean.
AB  - In developing bean (Phaseolus vulgaris) seeds, phloem-imported nutrients move in
      the symplast from sieve elements to the ground parenchyma cells where they are
      transported across the plasma membrane into the seed apoplast. To study the
      mechanisms underlying this transport, channel currents in ground parenchyma
      protoplasts were characterized using patch clamp. A fast-activating outward
      current was found in all protoplasts, whereas a slowly activating outward current
      was observed in approximately 25% of protoplasts. The two currents had low
      selectivity for univalent cations, but the slow current was more selective for
      K(+) over Cl(-) (P(K):P(Cl) = 3.6-4.2) than the fast current (P(K):P(Cl) = 1.8
      2.5) and also displayed Ca(2+) selectivity. The slow current was blocked by
      Ba(2+), whereas both currents were blocked by Gd(3+) and La(3+). Efflux of K(+)
      from seed coat halves was inhibited 25% by Gd(3+) and La(3+) but was stimulated
      by Ba(2+) and Cs(+), suggesting that only the fast current may be a component in
      the pathway for K(+) release. An "instantaneous" inward current observed in all
      protoplasts exhibited similar pharmacology and permeability for univalent cations
      to the fast outward current. In outside-out patches, two classes of
      depolarization-activated cation-selective channels were observed: one slowly
      activating of low conductance (determined from nonstationary noise to be 2.4 pS)
      and another with conductances 10-fold higher. Both channels occurred at high
      density. The higher conductance channel in 10 mM KCl had P(K):P(Cl) = 2.8. Such
      nonselective channels in the seed coat ground parenchyma cell could function to
      allow some of the efflux of phloem-imported univalent ions into the seed
      apoplast.

PMID- 11842144
TI  - Electrophysiological analysis of cloned cyclic nucleotide-gated ion channels.
AB  - Electrophysiological studies were conducted on the cloned plant cyclic nucleotide
      gated ion channels AtCNGC2 and AtCNGC1 from Arabidopsis, and NtCBP4 from tobacco
      (Nicotiana tobacum). The nucleotide coding sequences for these proteins were
      expressed in Xenopus laevis oocytes or HEK 293 cells. Channel characteristics
      were evaluated using voltage clamp analysis of currents in the presence of cAMP.
      AtCNGC2 was demonstrated to conduct K(+) and other monovalent cations, but
      exclude Na(+); this conductivity profile is unique for any ion channel not
      possessing the amino acid sequence found in the selectivity filter of K(+)
      selective ion channels. Application of cAMP evoked currents in membrane patches
      of oocytes injected with AtCNGC2 cRNA. Direct activation of the channel by cyclic
      nucleotide, demonstrated by application of cyclic nucleotide to patches of
      membranes expressing such channels, is a hallmark characteristic of this ion
      channel family. Voltage clamp studies (two-electrode configuration) demonstrated
      that AtCNGC1 and NtCBP4 are also cyclic nucleotide-gated channels. Addition of a
      lipophilic analog of cAMP to the perfusion bath of oocytes injected with NtCBP4
      and AtCNGC1 cRNAs induced inward rectified, noninactivating K(+) currents.

PMID- 11842145
TI  - Inactivation of the phloem-specific Dof zinc finger gene DAG1 affects response to
      light and integrity of the testa of Arabidopsis seeds.
AB  - We show here that seeds from the knockout mutant of the Arabidopsis DAG1 gene
      encoding a Dof zinc finger transcription factor have an altered response to red
      and far-red light. Mutant dag1 seeds are induced to germinate by much lower red
      light fluence rates, and germination reaches more quickly a point where it is
      independent of phytochrome signaling. Moreover, although microscopic analysis
      reveals no obvious structural alterations in the seed coat (testa) of dag1 seeds,
      staining assays with different dyes point to an abnormal fragility of the testa.
      By extensive in situ mRNA hybridization analysis we show here that the gene,
      which is not expressed in the embryo, is specifically expressed in the phloem of
      all organs of the mother plant.

PMID- 11842147
TI  - Differential substrate inhibition couples kinetically distinct 4
      coumarate:coenzyme a ligases with spatially distinct metabolic roles in quaking
      aspen.
AB  - 4-Coumarate:coenzyme A ligase (4CL) activates hydroxycinnamates for entry into
      phenylpropanoid branchways that support various metabolic activities, including
      lignification and flavonoid biosynthesis. However, it is not clear whether and
      how 4CL proteins with their broad substrate specificities fulfill the specific
      hydroxycinnamate requirements of the branchways they supply. Two tissue-specific
      4CLs, Pt4CL1 and Pt4CL2, have previously been cloned from quaking aspen (Populus
      tremuloides Michx.), but whether they are catalytically adapted for the
      distinctive metabolic roles they are thought to support is not apparent from
      published biochemical data. Therefore, single- and mixed-substrate assays were
      conducted to determine whether the 4CLs from aspen exhibit clear catalytic
      identities under certain metabolic circumstances. Recombinant Pt4CL1 and Pt4CL2
      exhibited the expected preference for p-coumarate in single-substrate assays, but
      strong competitive inhibition favored utilization of caffeate and p-coumarate,
      respectively, in mixed-substrate assays. The Pt4CL1 product, caffeoyl-CoA,
      predominated in mixed-substrate assays with xylem extract, and this was
      consistent with the near absence of Pt4CL2 expression in xylem tissue as
      determined by in situ hybridization. It is interesting that the Pt4CL2 product p
      coumaroyl-CoA predominated in assays with developing leaf extract, although in
      situ hybridization revealed that both genes were coexpressed. The xylem extract
      and recombinant 4CL1 data allow us to advance a mechanism by which 4CL1 can
      selectively utilize caffeate for the support of monolignol biosynthesis in
      maturing xylem and phloem fibers. Loblolly pine (Pinus taeda), in contrast,
      possesses a single 4CL protein exhibiting broad substrate specificity in mixed
      substrate assays. We discuss these 4CL differences in terms of the contrasts in
      lignification between angiosperm trees and their gymnosperm progenitors.

PMID- 11842146
TI  - AtREM1, a member of a new family of B3 domain-containing genes, is preferentially
      expressed in reproductive meristems.
AB  - We have isolated and characterized AtREM1, the Arabidopsis ortholog of the
      cauliflower (Brassica oleracea) BoREM1. AtREM1 belongs to a large gene family of
      more than 20 members in Arabidopsis. The deduced AtREM1 protein contains several
      repeats of a B3-related domain, and it could represent a new class of regulatory
      proteins only found in plants. Expression of AtREM1 is developmentally regulated,
      being first localized in a few central cells of vegetative apical meristems, and
      later expanding to the whole inflorescence meristem, as well as primordia and
      organs of third and fourth floral whorls. This specific expression pattern
      suggests a role in the organization of reproductive meristems, as well as during
      flower organ development.

PMID- 11842148
TI  - Functional analysis of the early steps of carotenoid biosynthesis in tobacco.
AB  - Carotenoids contribute to energy transduction in the light harvesting complexes
      and serve in protection from excess light fluence. Because of the importance of
      carotenoids, the genes encoding enzymes of carotenoid biosynthesis in higher
      plants are potential targets for herbicides. To obtain further insight into
      tobacco carotenoid biosynthesis and to investigate and prioritize potential
      herbicide targets in the pathway, the effects of changed phytoene synthase (PSY)
      and phytoene desaturase (PDS) gene expression were studied in transgenic tobacco
      (Nicotiana tabacum Petit Havana SR1) plants. Genes for both enzymes were cloned
      from tobacco, and surprisingly two functional PSY genes were found. Transgenic
      tobacco plants constitutively expressing these genes in both sense and antisense
      orientations were examined regarding phenotype, carotenoid content and transcript
      levels of carotene biosynthesis genes. Overexpression of either psy gene resulted
      in severe phenotypic effects including dwarfism, altered leaf morphology, and
      pigmentation. A correlation among phenotype, transcript level, and metabolic
      profile was demonstrated by comparison of hemizygous and homozygous plants from
      the same transformation event. Antisense expression of PSY and PDS also caused
      lethal phenotypes. Transcript levels of other carotene biosynthesis genes
      remained unaltered in the transgenic mutant. Phytoene accumulated in plants
      expressing antisense RNA to pds. However, elevated levels of phytoene were
      detected suggesting an increase in metabolic flux into this pathway.

PMID- 11842149
TI  - The N-terminal region of Arabidopsis cystathionine gamma-synthase plays an
      important regulatory role in methionine metabolism.
AB  - Cystathionine gamma-synthase (CGS) is a key enzyme of Met biosynthesis in
      bacteria and plants. Aligning the amino acid sequences revealed that the plant
      enzyme has an extended N-terminal region that is not found in the bacterial
      enzyme. However, this region is not essential for the catalytic activity of this
      enzyme, as deduced from the complementation test of an Escherichia coli CGS
      mutant. To determine the function of this N-terminal region, we overexpressed
      full-length Arabidopsis CGS and its truncated version that lacks the N-terminal
      region in transgenic tobacco (Nicotiana tabacum) plants. Transgenic plants
      expressing both types of CGS had a significant higher level of Met, S-methyl-Met,
      and Met content in their proteins. However, although plants expressing full
      length CGS showed the same phenotype and developmental pattern as wild-type
      plants, those expressing the truncated CGS showed a severely abnormal phenotype.
      These abnormal plants also emitted high levels of Met catabolic products,
      dimethyl sulfide and carbon disulfide. The level of ethylene, the Met-derived
      hormone, was 40 times higher than in wild-type plants. Since the alien CGS was
      expressed at comparable levels in both types of transgenic plants, we further
      suggest that post-translational modification(s) occurs in this N-terminal region,
      which regulate CGS and/or Met metabolism. More specifically, since the absence of
      the N-terminal region leads to an impaired Met metabolism, the results further
      suggest that this region plays a role in protecting plants from a high level of
      Met catabolic products such as ethylene.

PMID- 11842150
TI  - Oxygen deficiency responsive gene expression in Chlamydomonas reinhardtii through
      a copper-sensing signal transduction pathway.
AB  - Chlamydomonas reinhardtii activates Cpx1, Cyc6, and Crd1, encoding, respectively,
      coproporphyrinogen oxidase, cytochrome c(6), and a novel di-iron enzyme when
      transferred to oxygen-deficient growth conditions. This response is
      physiologically relevant because C. reinhardtii experiences these growth
      conditions routinely, and furthermore, one of the target genes, Crd1, is
      functionally required for normal growth under oxygen-depleted conditions. The
      same genes are activated also in response to copper-deficiency through copper
      response elements that function as target sites for a transcriptional activator.
      The core of the copper-response element, GTAC, is required also for the hypoxic
      response, as is a trans-acting locus, CRR1. Mercuric ions, which antagonize the
      copper-deficiency response, also antagonize the oxygen-deficiency response of
      these target genes. Taken together, these observations suggest that the oxygen-
      and copper-deficiency responses share signal transduction components.
      Nevertheless, whereas the copper-response element is sufficient for the
      nutritional copper response, the oxygen-deficiency response requires, in
      addition, a second cis-element, indicating that the response to oxygen depletion
      is not identical to the nutritional copper response. The distinction between the
      two responses is also supported by comparative analysis of the response of the
      target genes, Cyc6, Cpx1, and Crd1, to copper versus oxygen deficiency. A Crr1
      independent pathway for Hyd1 expression in oxygen-depleted C. reinhardtii
      demonstrates the existence of multiple oxygen/redox-responsive circuits in this
      model organism.

PMID- 11842151
TI  - Arabidopsis seedling growth, storage lipid mobilization, and photosynthetic gene
      expression are regulated by carbon:nitrogen availability.
AB  - The objective of the current work was to establish the degree to which the
      effects of carbon and nitrogen availability on Arabidopsis seedling growth and
      development are due to these nutrients acting independently or together. Growth
      of seedlings on low (0.1 mM) nitrogen results in a significant reduction of
      seedling and cotyledon size, fresh weight, chlorophyll, and anthocyanin content
      but a slight increase in endogenous sugars. The addition of 100 mM sucrose (Suc)
      to the nitrogen-depleted growth media results in a further reduction in cotyledon
      size and chlorophyll content and an overall increase in anthocyanins and
      endogenous sugars. Storage lipid breakdown is almost completely blocked in
      seedlings grown on low nitrogen and 100 mM Suc and is significantly inhibited
      when seedlings are grown on either low nitrogen or high Suc. Carbohydrate
      repression of photosynthetic gene expression can only be observed under low
      nitrogen conditions. Low (0.1 mM) nitrogen in the absence of exogenous
      carbohydrate results in a significant decrease in chlorophyll a/b-binding protein
      and ribulose bisphosphate carboxylase small subunit gene transcript levels. Thus,
      carbon to nitrogen ratio rather than carbohydrate status alone appears to play
      the predominant role in regulating various aspects of seedling growth including
      storage reserve mobilization and photosynthetic gene expression.

PMID- 11842152
TI  - Resistance against herbicide isoxaben and cellulose deficiency caused by distinct
      mutations in same cellulose synthase isoform CESA6.
AB  - Isoxaben is a pre-emergence herbicide that inhibits cellulose biosynthesis in
      higher plants. Two loci identified by isoxaben-resistant mutants (ixr1-1, ixr1-2,
      and ixr2-1) in Arabidopsis have been reported previously. IXR1 was recently shown
      to encode the cellulose synthase catalytic subunit CESA3 (W.-R. Scheible, R.
      Eshed, T. Richmond, D. Delmer, and C. Somerville [2001] Proc Natl Acad Sci USA
      98: 10079-10084). Here, we report on the cloning of IXR2, and show that it
      encodes another cellulose synthase isoform, CESA6. ixr2-1 carries a mutation
      substituting an amino acid close to the C terminus of CESA6 that is highly
      conserved among CESA family members. Transformation of wild-type plants with the
      mutated gene and not with the wild-type gene conferred increased resistance
      against the herbicide. The simplest interpretation for the existence of these two
      isoxaben-resistant loci is that CESA3 and CESA6 have redundant functions.
      However, loss of function procuste1 alleles of CESA6 were previously shown to
      have a strong growth defect and reduced cellulose content in roots and dark-grown
      hypocotyls. This indicates that in these mutants, the presence of CESA3 does not
      compensate for the absence of CESA6 in roots and dark-grown hypocotyls, which
      argues against redundant functions for CESA3 and CESA6. Together, these
      observations are compatible with a model in which CESA6 and CESA3 are active as a
      protein complex.

PMID- 11842153
TI  - Abscisic acid determines basal susceptibility of tomato to Botrytis cinerea and
      suppresses salicylic acid-dependent signaling mechanisms.
AB  - Abscisic acid (ABA) is one of the plant hormones involved in the interaction
      between plants and pathogens. In this work, we show that tomato (Lycopersicon
      esculentum Mill. cv Moneymaker) mutants with reduced ABA levels (sitiens plants)
      are much more resistant to the necrotrophic fungus Botrytis cinerea than wild
      type (WT) plants. Exogenous application of ABA restored susceptibility to B.
      cinerea in sitiens plants and increased susceptibility in WT plants. These
      results indicate that ABA plays a major role in the susceptibility of tomato to
      B. cinerea. ABA appeared to interact with a functional plant defense response
      against B. cinerea. Experiments with transgenic NahG tomato plants and
      benzo(1,2,3)thiadiazole-7-carbothioic acid demonstrated the importance of
      salicylic acid in the tomato-B. cinerea interaction. In addition, upon infection
      with B. cinerea, sitiens plants showed a clear increase in phenylalanine ammonia
      lyase activity, which was not observed in infected WT plants, indicating that the
      ABA levels in healthy WT tomato plants partly repress phenylalanine ammonia lyase
      activity. In addition, sitiens plants became more sensitive to
      benzo(1,2,3)thiadiazole-7-carbothioic acid root treatment. The threshold values
      for PR1a gene expression declined with a factor 10 to 100 in sitiens compared
      with WT plants. Thus, ABA appears to negatively modulate the salicylic acid
      dependent defense pathway in tomato, which may be one of the mechanisms by which
      ABA levels determine susceptibility to B. cinerea.

PMID- 11842154
TI  - Mutations in two independent genes lead to suppression of the shoot apical
      meristem in maize.
AB  - The shoot apical meristem (SAM), initially formed during embryogenesis, gives
      rise to the aboveground portion of the maize (Zea mays) plant. The shootless
      phenotype (sml) described here is caused by disruption of SAM formation due to
      the synergistic interaction of mutations at two genetic loci. Seedlings must be
      homozygous for both sml (shootmeristemless), and the unlinked dgr (distorted
      growth) loci for a SAM-less phenotype to occur. Seedlings mutant only for sml are
      impaired in their morphogenesis to different extents, whereas the dgr mutation
      alone does not have a recognisable phenotype. Thus, dgr can be envisaged as being
      a dominant modifier of sml and the 12 (normal):3 (distorted growth):1 (shoot
      meristemless) segregation observed in the F(2) of the double heterozygote is the
      result of the interaction between the sml and dgr genes. Other segregation
      patterns were also observed in the F(2), suggesting instability of the dgr gene.
      Efforts to rescue mutant embryos by growth on media enriched with hormones have
      been unsuccessful so far. However, mutant roots grow normally on medium
      supplemented with kinetin at a concentration that suppresses wild-type root
      elongation, suggesting possible involvement of the mutant in the reception or
      transduction of the kinetin signal or transport of the hormone. The shootless
      mutant appears to be a valuable tool with which to investigate the organization
      of the shoot meristem in monocots as well as a means to assay the origins and
      relationships between organs such as the scutellum, the coleoptile, and leaves
      that are initiated during the embryogenic process.

PMID- 11842155
TI  - The plastidic pentose phosphate translocator represents a link between the
      cytosolic and the plastidic pentose phosphate pathways in plants.
AB  - Plastids are the site of the reductive and the oxidative pentose phosphate
      pathways, which both generate pentose phosphates as intermediates. A plastidic
      transporter from Arabidopsis has been identified that is able to transport, in
      exchange with inorganic phosphate or triose phosphates, xylulose 5-phosphate (Xul
      5-P) and, to a lesser extent, also ribulose 5-phosphate, but does not accept
      ribose 5-phosphate or hexose phosphates as substrates. Under physiological
      conditions, Xul-5-P would be the preferred substrate. Therefore, the translocator
      was named Xul-5-P/phosphate translocator (XPT). The XPT shares only approximately
      35% to 40% sequence identity with members of both the triose phosphate
      translocator and the phosphoenolpyruvate/phosphate translocator classes, but a
      higher identity of approximately 50% to glucose 6-phosphate/phosphate
      translocators. Therefore, it represents a fourth group of plastidic phosphate
      translocators. Database analysis revealed that plant cells contain, in addition
      to enzymes of the oxidative branch of the oxidative pentose phosphate pathway,
      ribose 5-phosphate isomerase and ribulose 5-phosphate epimerase in both the
      cytosol and the plastids, whereas the transketolase and transaldolase converting
      the produced pentose phosphates to triose phosphates and hexose phosphates are
      probably solely confined to plastids. It is assumed that the XPT function is to
      provide the plastidic pentose phosphate pathways with cytosolic carbon skeletons
      in the form of Xul-5-P, especially under conditions of a high demand for
      intermediates of the cycles.

PMID- 11842156
TI  - Endogenous Nod-factor-like signal molecules promote early somatic embryo
      development in Norway spruce.
AB  - Embryogenic cultures of Norway spruce (Picea abies) are composed of pro
      embryogenic masses (PEMs) and somatic embryos of various developmental stages.
      Auxin is important for PEM formation and proliferation. In this report we show
      that depletion of auxin blocks PEM development and causes large-scale cell death.
      Extracts of the media conditioned by embryogenic cultures stimulate development
      of PEM aggregates in auxin-deficient cultures. Partial characterization of the
      conditioning factor shows that it is a lipophilic, low-molecular-weight molecule,
      which is sensitive to chitinase and contains GlcNAc residues. On the basis of
      this information, we propose that the factor is a lipophilic chitin
      oligosaccharide (LCO). The amount of LCO correlates to the developmental stages
      of PEMs and embryos, with the highest level in the media conditioned by
      developmentally blocked cultures. LCO is not present in nonembryogenic cultures.
      Cell death, induced by withdrawal of auxin, is suppressed by extra supply of
      endogenous LCO or Nod factor from Rhizobium sp. NGR234. The effect can be
      mimicked by a chitotetraose or chitinase from Streptomyces griseus. Taken
      together, our data suggest that endogenous LCO acts as a signal molecule
      stimulating PEM and early embryo development in Norway spruce.

PMID- 11842157
TI  - Temporal and spatial expression of a polygalacturonase during leaf and flower
      abscission in oilseed rape and Arabidopsis.
AB  - During leaf abscission in oilseed rape (Brassica napus), cell wall degradation is
      brought about by the action of several hydrolytic enzymes. One of these is
      thought to be polygalacturonase (PG). Degenerate primers were used to isolate a
      PG cDNA fragment by reverse transcriptase-polymerase chain reaction from RNA
      extracted from ethylene-promoted leaf abscission zones (AZs), and in turn a full
      length clone (CAW471) from an oilseed rape AZ cDNA library. The highest homology
      of this cDNA (82%) was to an Arabidopsis sequence that was predicted to encode a
      PG protein. Analysis of expression revealed that CAW471 mRNA accumulated in the
      AZ of leaves and reached a peak 24 h after ethylene treatment. Ethylene-promoted
      leaf abscission in oilseed rape was not apparent until 42 h after exposure to the
      gas, reaching 50% at 48 h and 100% by 56 h. In floral organ abscission,
      expression of CAW471 correlated with cell separation. Genomic libraries from
      oilseed rape and Arabidopsis were screened with CAW471 and the respective genomic
      clones PGAZBRAN and PGAZAT isolated. Characterization of these PG genes revealed
      that they had substantial homology within both the coding regions and in the 5'
      upstream sequences. Fusion of a 1,476-bp 5'-upstream sequence of PGAZAT to beta
      glucuronidase or green fluorescent protein and transformation of Arabidopsis
      revealed that this fragment was sufficient to drive expression of these reporter
      genes in the AZs at the base of the anther filaments, petals, and sepals.

PMID- 11842158
TI  - Overexpression of a 9-cis-epoxycarotenoid dioxygenase gene in Nicotiana
      plumbaginifolia increases abscisic acid and phaseic acid levels and enhances
      drought tolerance.
AB  - The plant hormone abscisic acid (ABA) plays important roles in seed maturation
      and dormancy and in adaptation to a variety of environmental stresses. An effort
      to engineer plants with elevated ABA levels and subsequent stress tolerance is
      focused on the genetic manipulation of the cleavage reaction. It has been shown
      in bean (Phaseolus vulgaris) that the gene encoding the cleavage enzyme (PvNCED1)
      is up-regulated by water stress, preceding accumulation of ABA. Transgenic wild
      tobacco (Nicotiana plumbaginifolia Viv.) plants were produced that overexpress
      the PvNCED1 gene either constitutively or in an inducible manner. The
      constitutive expression of PvNCED1 resulted in an increase in ABA and its
      catabolite, phaseic acid (PA). When the PvNCED1 gene was driven by the
      dexamethasone (DEX)-inducible promoter, a transient induction of PvNCED1 message
      and accumulation of ABA and PA were observed in different lines after application
      of DEX. Accumulation of ABA started to level off after 6 h, whereas the PA level
      continued to increase. In the presence of DEX, seeds from homozygous transgenic
      line TN1 showed a 4-d delay in germination. After spraying with DEX, the detached
      leaves from line TN1 had a drastic decrease in their water loss relative to
      control leaves. These plants also showed a marked increase in their tolerance to
      drought stress. These results indicate that it is possible to manipulate ABA
      levels in plants by overexpressing the key regulatory gene in ABA biosynthesis
      and that stress tolerance can be improved by increasing ABA levels.

PMID- 11842159
TI  - Salicylic acid has cell-specific effects on tobacco mosaic virus replication and
      cell-to-cell movement.
AB  - Tobacco mosaic virus (TMV) and Cucumber mosaic virus expressing green fluorescent
      protein (GFP) were used to probe the effects of salicylic acid (SA) on the cell
      biology of viral infection. Treatment of tobacco with SA restricted TMV.GFP to
      single-epidermal cell infection sites for at least 6 d post inoculation but did
      not affect infection sites of Cucumber mosaic virus expressing GFP.
      Microinjection experiments, using size-specific dextrans, showed that SA cannot
      inhibit TMV movement by decreasing the plasmodesmatal size exclusion limit. In SA
      treated transgenic plants expressing TMV movement protein, TMV.GFP infection
      sites were larger, but they still consisted overwhelmingly of epidermal cells.
      TMV replication was strongly inhibited in mesophyll protoplasts isolated from SA
      treated nontransgenic tobacco plants. Therefore, it appears that SA has distinct
      cell type-specific effects on virus replication and movement in the mesophyll and
      epidermal cell layers, respectively. Thus, SA can have fundamentally different
      effects on the same pathogen in different cell types.

PMID- 11842160
TI  - A grapevine gene encoding a guard cell K(+) channel displays developmental
      regulation in the grapevine berry.
AB  - SIRK is a K(+) channel identified in grapevine (Vitis vinifera), belonging to the
      so-called Shaker family. The highest sequence similarities it shares with the
      members of this family are found with channels of the KAT type, although SIRK
      displays a small ankyrin domain. This atypical feature provides a key to
      understand the evolution of the plant Shaker family. Expression in Xenopus laevis
      oocytes indicated that SIRK is an inwardly rectifying channel displaying
      functional properties very similar to those of KAT2. The activity of SIRK
      promoter region fused to the GUS reporter gene was analyzed in both grapevine and
      Arabidopsis. Like other KAT-like channels, SIRK is expressed in guard cells. In
      Arabidopsis, the construct is also expressed in xylem parenchyma.
      Semiquantitative reverse transcriptase-polymerase chain reaction experiments
      indicated that SIRK transcript was present at low levels in the berry, during the
      first stages of berry growth. After veraison, the period of berry development
      that corresponds to the inception of ripening and that is associated with large
      biochemical and structural modifications, such as evolution of stomata in
      nonfunctional lenticels and degeneration of xylem vasculature, the transcript was
      no longer detected. The whole set of data suggests that in the berries SIRK is
      expressed in guard cells and, possibly, in xylem tissues. The encoded channel
      polypeptide could therefore play a role in the regulation of transpiration and
      water fluxes in grapevine fruits.

PMID- 11842161
TI  - FQR1, a novel primary auxin-response gene, encodes a flavin mononucleotide
      binding quinone reductase.
AB  - FQR1 is a novel primary auxin-response gene that codes for a flavin
      mononucleotide-binding flavodoxin-like quinone reductase. Accumulation of FQR1
      mRNA begins within 10 min of indole-3-acetic acid application and reaches a
      maximum of approximately 10-fold induction 30 min after treatment. This increase
      in FQR1 mRNA abundance is not diminished by the protein synthesis inhibitor
      cycloheximide, demonstrating that FQR1 is a primary auxin-response gene. Sequence
      analysis reveals that FQR1 belongs to a family of flavin mononucleotide-binding
      quinone reductases. Partially purified His-tagged FQR1 isolated from Escherichia
      coli catalyzes the transfer of electrons from NADH and NADPH to several
      substrates and exhibits in vitro quinone reductase activity. Overexpression of
      FQR1 in plants leads to increased levels of FQR1 protein and quinone reductase
      activity, indicating that FQR1 functions as a quinone reductase in vivo. In
      mammalian systems, glutathione S-transferases and quinone reductases are
      classified as phase II detoxification enzymes. We hypothesize that the auxin
      inducible glutathione S-transferases and quinone reductases found in plants also
      act as detoxification enzymes, possibly to protect against auxin-induced
      oxidative stress.

PMID- 11842162
TI  - Gravity-stimulated changes in auxin and invertase gene expression in maize
      pulvinal cells.
AB  - Maize (Zea mays) stem gravitropism involves differential elongation of cells
      within a highly specialized region, the stem internodal pulvinus. In the present
      study, we investigated factors that control gravitropic responses in this system.
      In the graviresponding pulvinus, hexose sugars (D-Glc and D-Fru) accumulated
      asymmetrically across the pulvinus. This correlated well with an asymmetric
      increase in acid invertase activity across the pulvinus. Northern analyses
      revealed asymmetric induction of one maize acid invertase gene, Ivr2, consistent
      with transcriptional regulation by gravistimulation. Several lines of evidence
      indicated that auxin redistribution, as a result of polar auxin transport, is
      necessary for gravity-stimulated Ivr2 transcript accumulation and differential
      cell elongation across the maize pulvinus. First, the auxin transport inhibitor,
      N-1-naphthylphthalamic acid, inhibited gravistimulated curvature and Ivr2
      transcript accumulation. Second, a transient gradient of free indole-3-acetic
      acid (IAA) across the pulvinus was apparent shortly after initiation of
      gravistimulation. This temporarily free IAA gradient appears to be important for
      differential cell elongation and Ivr2 transcript accumulation. This is based on
      the observation that N-1-naphthylphthalamic acid will not inhibit gravitropic
      responses when applied to pulvinus tissue after the free IAA gradient peak has
      occurred. Third, IAA alone can stimulate Ivr2 transcript accumulation in non
      gravistimulated pulvini. The gravity- and IAA-stimulated increase in Ivr2
      transcripts was sensitive to the protein synthesis inhibitor, cycloheximide.
      Based on these results, a two-phase model describing possible relationships
      between gravitropic curvature, IAA redistribution, and Ivr2 expression is
      presented.

PMID- 11842163
TI  - Biosynthesis and distribution of chlorophyll among the photosystems during
      recovery of the green alga Dunaliella salina from irradiance stress.
AB  - To elucidate the mechanism of an irradiance-dependent adjustment in the
      chlorophyll (Chl) antenna size of Dunaliella salina, we investigated the
      regulation of expression of the Chl a oxygenase (CAO) and light-harvesting
      complex b (Lhcb) genes as a function of Chl availability in the photosynthetic
      apparatus. After a high-light to low-light shift of the cultures, levels of both
      CAO and Lhcb transcripts were rapidly induced by about 6-fold and reached a high
      steady-state level within 1.5 h of the shift. This was accompanied by repair of
      photodamaged photosystem II (PSII) reaction centers, accumulation of Chl a and
      Chl b (4:1 ratio), photosystem I (PSI), light-harvesting complex, and by
      enlargement of the Chl antenna size of both photosystems. In gabaculine-treated
      cells, induction of CAO and Lhcb transcripts was not affected despite substantial
      inhibition in de novo Chl biosynthesis. However, cells were able to synthesize
      and accumulate some Chl a and Chl b (1:1 ratio), resulting in a marked lowering
      of the Chl a to Chl b ratio in the presence of this inhibitor. Assembly
      incorporation of light-harvesting complex and a corresponding Chl antenna size
      increase, mostly for the existing photosystems, was noted in the presence of
      gabaculine. Repair of photodamaged PSII was not affected by gabaculine. However,
      assembly accumulation of new PSI was limited under such conditions. These results
      suggest a coordinate regulation of CAO and Lhcb gene transcription by irradiance,
      independent of Chl availability. The results are discussed in terms of different
      signal transduction pathways for the regulation of the photosynthetic apparatus
      organization by irradiance.

PMID- 11842164
TI  - Transgenic production of epoxy fatty acids by expression of a cytochrome P450
      enzyme from Euphorbia lagascae seed.
AB  - Seed oils of a number of Asteraceae and Euphorbiaceae species are enriched in 12
      epoxyoctadeca-cis-9-enoic acid (vernolic acid), an unusual 18-carbon Delta(12)
      epoxy fatty acid with potential industrial value. It has been previously
      demonstrated that the epoxy group of vernolic acid is synthesized by the activity
      of a Delta(12)-oleic acid desaturase-like enzyme in seeds of the Asteraceae
      Crepis palaestina and Vernonia galamensis. In contrast, results from metabolic
      studies have suggested the involvement of a cytochrome P450 enzyme in vernolic
      acid synthesis in seeds of the Euphorbiaceae species Euphorbia lagascae. To
      clarify the biosynthetic origin of vernolic acid in E. lagascae seed, an
      expressed sequence tag analysis was conducted. Among 1,006 randomly sequenced
      cDNAs from developing E. lagascae seeds, two identical expressed sequence tags
      were identified that encode a cytochrome P450 enzyme classified as CYP726A1.
      Consistent with the seed-specific occurrence of vernolic acid in E. lagascae,
      mRNA corresponding to the CYP726A1 gene was abundant in developing seeds, but was
      not detected in leaves. In addition, expression of the E. lagascae CYP726A1 cDNA
      in Saccharomyces cerevisiae was accompanied by production of vernolic acid in
      cultures supplied with linoleic acid and an epoxy fatty acid tentatively
      identified as 12-epoxyoctadeca-9,15-dienoic acid (12-epoxy-18:2Delta(9,15)) in
      cultures supplied with alpha-linolenic acid. Consistent with this, expression of
      CYP726A1 in transgenic tobacco (Nicotiana tabacum) callus or somatic soybean
      (Glycine max) embryos resulted in the accumulation of vernolic acid and 12-epoxy
      18:2Delta(9,15). Overall, these results conclusively demonstrate that Asteraceae
      species and the Euphorbiaceae E. lagascae have evolved structurally unrelated
      enzymes to generate the Delta(12)-epoxy group of vernolic acid.

PMID- 11842165
TI  - Selenium assimilation and volatilization from selenocyanate-treated Indian
      mustard and muskgrass.
AB  - Selenocyanate (SeCN(-)) is a major contaminant in the effluents from some oil
      refineries, power plants, and in mine drainage water. In this study, we
      determined the potential of Indian mustard (Brassica juncea) and muskgrass (a
      macroalga, Chara canescens) for SeCN(-) phytoremediation in upland and wetland
      situations, respectively. The tolerance of Indian mustard to toxic levels of
      SeCN(-) was similar to or higher than other toxic forms of Se. Indian mustard
      treated with 20 microM SeCN(-) removed 30% (w/v) of the Se supplied in 5 d,
      accumulating 554 and 86 microg of Se g(-1) dry weight in roots and shoots,
      respectively. Under similar conditions, muskgrass removed approximately 9% (w/v)
      of the Se supplied as SeCN(-) and accumulated 27 microg of Se g(-1) dry weight. A
      biochemical pathway for SeCN(-) degradation was proposed for Indian mustard.
      Indian mustard and muskgrass efficiently degraded SeCN(-) as none of the Se
      accumulated by either organism remained in this form. Indian mustard accumulated
      predominantly organic Se, whereas muskgrass contained Se mainly as selenite and
      organic Se forms. Indian mustard produced volatile Se from SeCN(-) in the form of
      less toxic dimethylselenide. Se volatilization by Indian mustard accounted for
      only 0.7% (w/v) of the SeCN(-) removed, likely because the biochemical steps in
      the production of dimethylselenide from organic Se were rate limiting. Indian
      mustard is promising for the phytoremediation of SeCN(-) -contaminated soil and
      water because of its remarkable abilities to phytoextract SeCN(-) and degrade all
      the accumulated SeCN(-) to other Se forms.

PMID- 11842166
TI  - Diurnal and circadian regulation of putative potassium channels in a leaf moving
      organ.
AB  - In a search for potassium channels involved in light- and clock-regulated leaf
      movements, we cloned four putative K channel genes from the leaf-moving organs,
      pulvini, of the legume Samanea saman. The S. saman SPOCK1 is homologous to KCO1,
      an Arabidopsis two-pore-domain K channel, the S. saman SPORK1 is similar to SKOR
      and GORK, Arabidopsis outward-rectifying Shaker-like K channels, and the S. saman
      SPICK1 and SPICK2 are homologous to AKT2, a weakly-inward-rectifying Shaker-like
      Arabidopsis K channel. All four S. saman sequences possess the universal K
      channel-specific pore signature, TXXTXGYG, strongly suggesting a role in
      transmembrane K(+) transport. The four S. saman genes had different expression
      patterns within four leaf parts: "extensor" and "flexor" (the motor tissues), the
      leaf blades (mainly mesophyll), and the vascular bundle ("rachis"). Based on
      northern blot analysis, their transcript level was correlated with the rhythmic
      leaf movements: (a) all four genes were regulated diurnally (Spick2, Spork1, and
      Spock1 in extensor and flexor, Spick1 in extensor and rachis); (b) Spork1 and
      Spock1 rhythms were inverted upon the inversion of the day-night cycle; and (c)
      in extensor and/or flexor, the expression of Spork1, Spick1, and Spick2 was also
      under a circadian control. These findings parallel the circadian rhythm shown to
      govern the resting membrane K(+) permeability in extensor and flexor protoplasts
      and the susceptibility of this permeability to light stimulation (Kim et al.,
      1993). Thus, Samanea pulvinar motor cells are the first described system
      combining light and circadian regulation of K channels at the level of transcript
      and membrane transport.

PMID- 11842167
TI  - Extrinsic photosystem II carbonic anhydrase in maize mesophyll chloroplasts.
AB  - One form of carbonic anhydrase (CA) has been observed in maize (Zea mays)
      thylakoids and photosystem II (PSII)-enriched membranes. Here, we show that an
      antibody produced against a thylakoid lumen-targeted CA found in Chlamydomonas
      reinhardtii reacts with a single 33-kD polypeptide in maize thylakoids. With
      immunoblot analysis, we found that this single polypeptide could be identified
      only in mesophyll thylakoids and derived PSII membranes, but not in bundle sheath
      thylakoids. Likewise, a CA activity assay confirmed a large amount of activity in
      mesophyll, but not in bundle sheath membranes. Immunoblot analysis and CA
      activity assay showed that the maximum CA can be obtained in the supernatant of
      the PSII-enriched membranes washed with 1 M CaCl(2), the same procedure used to
      remove all extrinsic lumenal proteins from PSII. Because this CA reacts with an
      antibody to lumen-directed CA in C. reinhardtii, and because it can be removed
      with 1 M CaCl(2) wash, we refer to it tentatively as extrinsic CA. This is to
      distinguish it from another form of CA activity tightly bound to PSII membranes
      that remains after CaCl(2) wash, which has been described previously. The
      function of extrinsic CA is not clear. It is unlikely to have the same function
      as the cytoplasmic CA, which has been proposed to increase the HCO(-)(3)
      concentration for phosphoenolpyruvate carboxylase and the C(4) pathway. We
      suggest that because the extrinsic CA is associated only with thylakoids doing
      linear electron flow, it could function to produce the CO(2) or HCO(-)(3) needed
      for PSII activity.

PMID- 11842168
TI  - Biochemical and molecular characterization of a mutation that confers a decreased
      raffinosaccharide and phytic acid phenotype on soybean seeds.
AB  - A single, recessive mutation in soybean (Glycine max L. Merr.), which confers a
      seed phenotype of increased inorganic phosphate, decreased phytic acid, and a
      decrease in total raffinosaccharides, has been previously disclosed (S.A.
      Sebastian, P.S. Kerr, R.W. Pearlstein, W.D. Hitz [2000] Soy in Animal Nutrition,
      pp 56-74). The genetic lesion causing the multiple changes in seed phenotype is a
      single base change in the third base of the codon for what is amino acid residue
      396 of the mature peptide encoding a seed-expressed myo-inositol 1-phospate
      synthase gene. The base change causes residue 396 to change from lysine to
      asparagine. That amino acid change decreases the specific activity of the seed
      expressed myo-inositol 1-phosphate synthase by about 90%. Radio tracer
      experiments indicate that the supply of myo-inositol to the reaction, which
      converts UDP-galactose and myo-inositol to galactinol is a controlling factor in
      the conversion of total carbohydrate into the raffinosaccharides in both wild
      type and mutant lines. That same decrease in myo-inositol 1-phosphate synthetic
      capacity leads to a decreased capacity for the synthesis of myo-inositol
      hexaphosphate (phytic acid) and a concomitant increase in inorganic phosphate.

PMID- 11842172
TI  - Antisense RNA-mediated suppression of benzophenanthridine alkaloid biosynthesis
      in transgenic cell cultures of California poppy.
AB  - California poppy (Eschscholzia californica Cham.) cell cultures produce several
      benzophenanthridine alkaloids, such as sanguinarine, chelirubine, and macarpine,
      with potent pharmacological activity. Antisense constructs of genes encoding two
      enzymes involved in benzophenanthridine alkaloid biosynthesis, the berberine
      bridge enzyme (BBE) and N-methylcoclaurine 3'-hydroxylase (CYP80B1), were
      introduced separately into California poppy cell cultures. Transformed cell lines
      expressing antisense BBE or antisense CYP80B1 constructs and displaying low
      levels of BBE or CYP80B1 mRNAs, respectively, showed reduced accumulation of
      benzophenanthridine alkaloids compared with control cultures transformed with a
      beta-glucuronidase gene. Pathway intermediates were not detected in any of the
      transformed cell lines. The suppression of benzophenanthridine alkaloid
      biosynthesis using BBE or CYP80B1 antisense RNA constructs also reduced the
      growth rate of the cultures. Two-dimensional (1)H-nuclear magnetic resonance and
      in vivo (15)N-nuclear magnetic resonance spectroscopy showed no difference in the
      abundance of carbohydrate metabolites in the various transgenic cell lines.
      However, transformed cells with reduced benzophenanthridine alkaloid levels
      contained larger cellular pools of several amino acids including alanine,
      leucine, phenylalanine, threonine, and valine compared with controls. The
      relative abundance of tyrosine, from which benzophenanthridine alkaloids are
      derived, was less than 2-fold higher in antisense-suppressed cells relative to
      controls. These results show that alterations in the metabolic flux through
      benzophenanthridine alkaloid biosynthesis can affect the regulation of amino acid
      pools. These data provide new insight into the metabolic engineering of
      benzophenanthridine alkaloid pathways.

PMID- 11842169
TI  - Functional regions of rice heat shock protein, Oshsp16.9, required for conferring
      thermotolerance in Escherichia coli.
AB  - Rice (Oryza sativa) class I low-molecular mass (LMM) heat shock protein (HSP),
      Oshsp16.9, has been shown to be able to confer thermotolerance in Escherichia
      coli. To define the regions for this intriguing property, deletion mutants of
      this hsp have been constructed and overexpressed in E. coli XL1-blue cells after
      isopropyl beta-D-thioglactopyranoside induction. The deletion of amino acid
      residues 30 through 36 (PATSDND) in the N-terminal domain or 73 through 78
      (EEGNVL) in the consensus II domain of Oshsp16.9 led to the loss of chaperone
      activities and also rendered the E. coli incapable of surviving at 47.5 degrees
      C. To further investigate the function of these two domains, we determined the
      light scattering changes of Oshsp16.9 mutant proteins at 320 nm under heat
      treatment either by themselves or in the presence of a thermosensitive enzyme,
      citrate synthase. It was observed that regions of amino acid residues 30 through
      36 and 73 through 78 were responsible for stability of Oshsp16.9 and its
      interactions with other unfolded protein substrates, such as citrate synthase.
      Studies of two-point mutants of Oshsp16.9, GST-N74E73K and GST-N74E74K, indicate
      that amino acid residues 73 and 74 are an important part of the substrate-binding
      site of Oshsp16.9. Non-denaturing gel analysis of purified Oshsp16.9 revealed
      that oligomerization of Oshsp16.9 was necessary but not sufficient for its
      chaperone activity.

PMID- 11842170
TI  - Disruption of the actin cytoskeleton results in the promotion of gravitropism in
      inflorescence stems and hypocotyls of Arabidopsis.
AB  - The actin cytoskeleton is hypothesized to play a major role in gravity perception
      and transduction mechanisms in roots of plants. To determine whether actin
      microfilaments (MFs) are involved in these processes in stem-like organs, we
      studied gravitropism in Arabidopsis inflorescence stems and hypocotyls.
      Localization studies using Alexa Fluor-phalloidin in conjugation with confocal
      microscopy demonstrated a longitudinally and transversely oriented actin MF
      network in endodermal cells of stems and hypocotyls. Latrunculin B (Lat-B)
      treatment of hypocotyls caused depolymerization of actin MFs in endodermal cells
      and a significant reduction of hypocotyl growth rates. Actin MFs in Lat-B-treated
      inflorescence stems also were disrupted, but growth rates were not affected.
      Despite disruption of the actin cytoskeleton in these two organs, Lat-B-treated
      stems and hypocotyls exhibited a promotion of gravitropic curvature in response
      to reorientation. In contrast, Lat-B reduced gravitropic curvature in roots but
      also reduced the growth rate. Thus, in contrast to prevailing hypotheses, our
      results suggest that actin MFs are not a necessary component of gravitropism in
      inflorescence stems and hypocotyls. Furthermore, this is the first study to
      demonstrate a prominent actin MF network in endodermal cells in the putative
      gravity-perceiving cells in stems.

PMID- 11842171
TI  - Protection against heat stress-induced oxidative damage in Arabidopsis involves
      calcium, abscisic acid, ethylene, and salicylic acid.
AB  - Plants, in common with all organisms, have evolved mechanisms to cope with the
      problems caused by high temperatures. We examined specifically the involvement of
      calcium, abscisic acid (ABA), ethylene, and salicylic acid (SA) in the protection
      against heat-induced oxidative damage in Arabidopsis. Heat caused increased
      thiobarbituric acid reactive substance levels (an indicator of oxidative damage
      to membranes) and reduced survival. Both effects required light and were reduced
      in plants that had acquired thermotolerance through a mild heat pretreatment.
      Calcium channel blockers and calmodulin inhibitors increased these effects of
      heating and added calcium reversed them, implying that protection against heat
      induced oxidative damage in Arabidopsis requires calcium and calmodulin. Similar
      to calcium, SA, 1-aminocyclopropane-1-carboxylic acid (a precursor to ethylene),
      and ABA added to plants protected them from heat-induced oxidative damage. In
      addition, the ethylene-insensitive mutant etr-1, the ABA-insensitive mutant abi
      1, and a transgenic line expressing nahG (consequently inhibited in SA
      production) showed increased susceptibility to heat. These data suggest that
      protection against heat-induced oxidative damage in Arabidopsis also involves
      ethylene, ABA, and SA. Real time measurements of cytosolic calcium levels during
      heating in Arabidopsis detected no increases in response to heat per se, but
      showed transient elevations in response to recovery from heating. The magnitude
      of these calcium peaks was greater in thermotolerant plants, implying that these
      calcium signals might play a role in mediating the effects of acquired
      thermotolerance. Calcium channel blockers and calmodulin inhibitors added solely
      during the recovery phase suggest that this role for calcium is in protecting
      against oxidative damage specifically during/after recovery.

PMID- 11842173
TI  - Characterization of calcium oxalates generated as biominerals in cacti.
AB  - The chemical composition and morphology of solid material isolated from various
      Cactaceae species have been analyzed. All of the tested specimens deposited high
      purity calcium oxalate crystals in their succulent modified stems. These deposits
      occurred most frequently as round-shaped druses that sometimes coexist with
      abundant crystal sand in the tissue. The biominerals were identified either as
      CaC(2)O(4).2H(2)O (weddellite) or as CaC(2)O(4).H(2)O (whewellite). Seven
      different species from the Opuntioideae subfamily showed the presence of
      whewellite, and an equal number of species from the Cereoideae subfamily showed
      the deposition of weddellite. The chemical nature of these deposits was assessed
      by infrared spectroscopy. The crystal morphology of the crystals was visualized
      by both conventional light and scanning electron microscopy. Weddellite druses
      were made up of tetragonal crystallites, whereas those from whewellite were most
      often recognized by their acute points and general star-like shape. These studies
      clearly demonstrated that members from the main traditional subfamilies of the
      Cactaceae family could synthesize different chemical forms of calcium oxalate,
      suggesting a definite but different genetic control. The direct relationship
      established between a given Cactaceae species and a definite calcium oxalate
      biomineral seems to be a useful tool for plant identification and chemotaxonomy.

PMID- 11842174
TI  - Purification and identification of a 42-kilodalton abscisic acid-specific-binding
      protein from epidermis of broad bean leaves.
AB  - Purification of abscisic acid (ABA)-binding proteins is considered to constitute
      a major step toward isolating ABA receptors. We report here that an ABA-binding
      protein was for the first time, to our knowledge, purified from the epidermis of
      broad bean (Vicia faba) leaves via affinity chromatography. Sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis, isoelectric focusing electrophoresis,
      and isoelectric focusing/sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis two-dimensional electrophoresis of the purified ABA-binding
      protein all identified a single protein band with a molecular mass of 42 kD and
      an isoelectric point 4.86. The Scatchard plot for the purified protein showed a
      linear function with a maximum binding activity of 0.87 mol mol(-1) protein and
      an equilibrium dissociation constant of 21 nM, indicating that the purified
      protein may be a monomeric one, possessing one binding site. The ABA-binding
      protein was enriched more than 300-fold with a yield of 14%. (-)ABA and trans-ABA
      were substantially incapable of displacing (3)H-(+/-)ABA bound to the ABA-binding
      protein, and (+/-)ABA was less effective than (+)ABA in the competition. These
      findings allow establishment of the stereospecificity of the 42-kD protein and
      suggest its ABA receptor nature. Pretreatment of the guard cell protoplasts of
      broad bean leaves with the monoclonal antibody raised against the 42-kD protein
      significantly decreased the ABA specific-induced phospholipase D activity in a
      dose-dependent manner. This physiological significance provides more clear
      evidence for the potential ABA-receptor nature of the 42-kD protein.

PMID- 11842175
TI  - Flavone glucoside uptake into barley mesophyll and Arabidopsis cell culture
      vacuoles. Energization occurs by H(+)-antiport and ATP-binding cassette-type
      mechanisms.
AB  - In many cases, secondary plant products accumulate in the large central vacuole
      of plant cells. However, the mechanisms involved in the transport of secondary
      compounds are only poorly understood. Here, we demonstrate that the transport
      mechanisms for the major barley (Hordeum vulgare) flavonoid saponarin (apigenin 6
      C-glucosyl-7-O-glucoside) are different in various plant species: Uptake into
      barley vacuoles occurs via a proton antiport and is competitively inhibited by
      isovitexin (apigenin 6-C-glucoside), suggesting that both flavone glucosides are
      recognized by the same transporter. In contrast, the transport into vacuoles from
      Arabidopsis, which does not synthesize flavone glucosides, displays typical
      characteristics of ATP-binding cassette transporters. Transport of saponarin into
      vacuoles of both the species is saturable with a K(m) of 50 to 100 microM.
      Furthermore, the uptake of saponarin into vacuoles from a barley mutant
      exhibiting a strongly reduced flavone glucoside biosynthesis is drastically
      decreased when compared with the parent variety. Thus, the barley vacuolar
      flavone glucoside/H(+) antiporter could be modulated by the availability of the
      substrate. We propose that different vacuolar transporters may be responsible for
      the sequestration of species-specific/endogenous and nonspecific/xenobiotic
      secondary compounds in planta.

PMID- 11842176
TI  - Control of gibberellin levels and gene expression during de-etiolation in pea.
AB  - Gibberellin A(1) (GA(1)) levels drop significantly in wild-type pea (Pisum
      sativum) plants within 4 h of exposure to red, blue, or far-red light. This
      response is controlled by phytochrome A (phyA) (and not phyB) and a blue light
      receptor. GA(8) levels are increased in response to 4 h of red light, whereas the
      levels of GA(19), GA(20), and GA(29) do not vary substantially. Red light appears
      to control GA(1) levels by down-regulating the expression of Mendel's LE
      (PsGA3ox1) gene that controls the conversion of GA(20) to GA(1), and by up
      regulating PsGA2ox2, which codes for a GA 2-oxidase that converts GA(1) to GA(8).
      This occurs within 0.5 to 1 h of exposure to red light. Similar responses occur
      in blue light. The major GA 20-oxidase gene expressed in shoots, PsGA20ox1, does
      not show substantial light regulation, but does show up-regulation after 4 h of
      red light, probably as a result of feedback regulation. Expression of PsGA3ox1
      shows a similar feedback response, whereas PsGA2ox2 shows a feed-forward
      response. These results add to our understanding of how light reduces shoot
      elongation during de-etiolation.

PMID- 11842177
TI  - Dynamic and steady-state responses of inorganic nitrogen pools and NH(3) exchange
      in leaves of Lolium perenne and Bromus erectus to changes in root nitrogen
      supply.
AB  - Short- and long-term responses of inorganic N pools and plant-atmosphere NH(3)
      exchange to changes in external N supply were investigated in 11-week-old plants
      of two grass species, Lolium perenne and Bromus erectus, characteristic of N-rich
      and N-poor grassland ecosystems, respectively. A switch of root N source from NO(
      )(3)to NH(4)(+) caused within 3 h a 3- to 6-fold increase in leaf apoplastic
      NH(4)(+) concentration and a simultaneous decrease in apoplastic pH of about 0.4
      pH units in both species. The concentration of total extractable leaf tissue
      NH(4)(+) also increased two to three times within 3 h after the switch. Removal
      of exogenous NH(4)(+) caused the apoplastic NH(4)(+) concentration to decline
      back to the original level within 24 h, whereas the leaf tissue
      NH(4)(+)concentration decreased more slowly and did not reach the original level
      in 48 h. After growing for 5 weeks with a steady-state supply of NO(-)(3)or
      NH(4)(+), L. perenne were in all cases larger, contained more N, and utilized the
      absorbed N more efficiently for growth than B. erectus, whereas the two species
      behaved oppositely with respect to tissue concentrations of NO(-)(3), NH(4)(+),
      and total N. Ammonia compensation points were higher for B. erectus than for L.
      perenne and were in both species higher for NH(4)(+)- than for NO(-)(3)-grown
      plants. Steady-state levels of apoplastic NH(4)(+), tissue NH(4)(+), and NH(3)
      emission were significantly correlated. It is concluded that leaf apoplastic
      NH(4)(+) is a highly dynamic pool, closely reflecting changes in the external N
      supply. This rapid response may constitute a signaling system coordinating leaf N
      metabolism with the actual N uptake by the roots and the external N availability.

PMID- 11842178
TI  - Manipulation of strawberry fruit softening by antisense expression of a pectate
      lyase gene.
AB  - Strawberry (Fragaria x ananassa, Duch., cv Chandler) is a soft fruit with a short
      postharvest life, mainly due to a rapid lost of firm texture. To control the
      strawberry fruit softening, we obtained transgenic plants that incorporate an
      antisense sequence of a strawberry pectate lyase gene under the control of the
      35S promoter. Forty-one independent transgenic lines (Apel lines) were obtained,
      propagated in the greenhouse for agronomical analysis, and compared with control
      plants, non-transformed plants, and transgenic lines transformed with the pGUSINT
      plasmid. Total yield was significantly reduced in 33 of the 41 Apel lines. At the
      stage of full ripen, no differences in color, size, shape, and weight were
      observed between Apel and control fruit. However, in most of the Apel lines,
      ripened fruits were significantly firmer than controls. Six Apel lines were
      selected for further analysis. In all these lines, the pectate lyase gene
      expression in ripened fruit was 30% lower than in control, being totally
      suppressed in three of them. Cell wall material isolated from ripened Apel fruit
      showed a lower degree of in vitro swelling and a lower amount of ionically bound
      pectins than control fruit. An analysis of firmness at three different stages of
      fruit development (green, white, and red) showed that the highest reduction of
      softening in Apel fruit occurred during the transition from the white to the red
      stage. The postharvest softening of Apel fruit was also diminished. Our results
      indicate that pectate lyase gene is an excellent candidate for biotechnological
      improvement of fruit softening in strawberry.

PMID- 11842179
TI  - Cyclic electron flow around photosystem I in C(3) plants. In vivo control by the
      redox state of chloroplasts and involvement of the NADH-dehydrogenase complex.
AB  - Cyclic electron flow around photosystem (PS) I has been widely described in vitro
      in chloroplasts or thylakoids isolated from C(3) plant leaves, but its occurrence
      in vivo is still a matter of debate. Photoacoustic spectroscopy and kinetic
      spectrophotometry were used to analyze cyclic PS I activity in tobacco (Nicotiana
      tabacum cv Petit Havana) leaf discs illuminated with far-red light. Only a very
      weak activity was measured in air with both techniques. When leaf discs were
      placed in anaerobiosis, a high and rapid cyclic PS I activity was measured. The
      maximal energy storage in far-red light increased to 30% to 50%, and the half
      time of the P(700) re-reduction in the dark decreased to around 400 ms; these
      values are comparable with those measured in cyanobacteria and C(4) plant leaves
      in aerobiosis. The stimulatory effect of anaerobiosis was mimicked by
      infiltrating leaves with inhibitors of mitochondrial respiration or of the
      chlororespiratory oxidase, therefore, showing that changes in the redox state of
      intersystem electron carriers tightly control the rate of PS I-driven cyclic
      electron flow in vivo. Measurements of energy storage at different modulation
      frequencies of far-red light showed that anaerobiosis-induced cyclic PS I
      activity in leaves of a tobacco mutant deficient in the plastid Ndh complex was
      kinetically different from that of the wild type, the cycle being slower in the
      former leaves. We conclude that the Ndh complex is required for rapid electron
      cycling around PS I.

PMID- 11842180
TI  - Chlorophyll biosynthesis. Expression of a second chl I gene of magnesium
      chelatase in Arabidopsis supports only limited chlorophyll synthesis.
AB  - Magnesium (Mg) chelatase is a heterotrimeric enzyme complex that catalyzes a key
      regulatory and enzymatic reaction in chlorophyll biosynthesis, the insertion of
      Mg(2+) into protoporphyrin IX. Studies of the enzyme complex reconstituted in
      vitro have shown that all three of its subunits, CHL I, CHL D, and CHL H, are
      required for enzymatic activity. However, a new T-DNA knockout mutant of the
      chlorina locus, ch42-3 (Chl I), in Arabidopsis is still able to accumulate some
      chlorophyll despite the absence of Chl I mRNA and protein. In barley (Hordeum
      vulgare), CHL I is encoded by a single gene. We have identified an open reading
      frame that apparently encodes a second Chl I gene, Chl I2. Chl I1 and Chl I2 mRNA
      accumulate to similar levels in wild type, yet CHL I2 protein is not detectable
      in wild type or ch42-3, although the protein is translated and stromally
      processed as shown by in vivo pulse labeling and in vitro chloroplast imports. It
      is surprising that CHL D accumulates to wild-type levels in ch42-3, which is in
      contrast to reports that CHL D is unstable in CHL I-deficient backgrounds of
      barley. Our results show that limited Mg chelatase activity and CHL D
      accumulation can occur without detectable CHL I, despite its obligate requirement
      in vitro and its proposed chaperone-like stabilization and activation of CHL D.
      Thus, the unusual post-translational regulation of the CHL I2 protein provides an
      opportunity to study the different steps involved in stabilization and activation
      of the heterotrimeric Mg chelatase in vivo.

PMID- 11842181
TI  - Mechanism of action and NAD+-binding mode revealed by the crystal structure of L
      histidinol dehydrogenase.
AB  - The histidine biosynthetic pathway is an ancient one found in bacteria,
      archaebacteria, fungi, and plants that converts 5-phosphoribosyl 1-pyrophosphate
      to l-histidine in 10 enzymatic reactions. This pathway provided a paradigm for
      the operon, transcriptional regulation of gene expression, and feedback
      inhibition of a pathway. l-histidinol dehydrogenase (HisD, EC ) catalyzes the
      last two steps in the biosynthesis of l-histidine: sequential NAD-dependent
      oxidations of l-histidinol to l-histidinaldehyde and then to l-histidine. HisD
      functions as a homodimer and requires the presence of one Zn(2+) cation per
      monomer. We have determined the three-dimensional structure of Escherichia coli
      HisD in the apo state as well as complexes with substrate, Zn(2+), and NAD(+)
      (best resolution is 1.7 A). Each monomer is made of four domains, whereas the
      intertwined dimer possibly results from domain swapping. Two domains display a
      very similar incomplete Rossmann fold that suggests an ancient event of gene
      duplication. Residues from both monomers form the active site. Zn(2+) plays a
      crucial role in substrate binding but is not directly involved in catalysis. The
      active site residue His-327 participates in acid-base catalysis, whereas Glu-326
      activates a water molecule. NAD(+) binds weakly to one of the Rossmann fold
      domains in a manner different from that previously observed for other proteins
      having a Rossmann fold.

PMID- 11842183
TI  - A liposome-based therapeutic vaccine against beta -amyloid plaques on the
      pancreas of transgenic NORBA mice.
AB  - Immune tolerance to beta-amyloid (Abeta) was broken in NORBA transgenic mice
      presenting Abeta plaques on their pancreases. Vaccination of Black C57, BALB/c,
      and NORBA mice with the synthetic Abeta(1-16) sequence modified by covalently
      attaching two palmitoyl residues at each end of the peptide, subsequently
      reconstituted in liposomes-Lipid A elicited titers of 1:5,000 of anti-Abeta(1-16)
      antibodies within 10 weeks after the first inoculation. On direct interaction,
      sera with antibody titers of 1:5,000 solubilized in vitro up to 80% of preformed
      Abeta(1-42) aggregates. Cryosections of pancreases of unvaccinated NORBA mice
      show, on staining with Thioflavin T, extensive areas of high-intensity
      fluorescence in the acinar cell fields. Quantitation of the average fluorescence
      intensity in each section indicated that: (i) whereas nonvaccinated NORBA mice
      develop plaques within 45-60 days after birth, vaccinated 8-week-old NORBA mice
      did not develop amyloid plaques on their pancreases over a period of 7 months;
      (ii) cryosections from pancreases of 9- and 15-month-old vaccinated NORBA mice
      showed less than 50% of the fluorescence shown by cryosections from unvaccinated
      animals of the same age. The results indicate that palmitoylated Abeta peptides,
      reconstituted in liposomes-lipid A, are highly immunogenic, eliciting
      "therapeutic" antibody titers within 3 months of the first inoculation and
      preventing amyloid plaque formation in young animals or significantly reducing
      existing plaques in older transgenic mice. Possible implications for the therapy
      of Alzheimer's disease are discussed.

PMID- 11842182
TI  - Conservation of Pax 6 function and upstream activation by Notch signaling in eye
      development of frogs and flies.
AB  - Loss of Pax 6 function leads to an eyeless phenotype in both mammals and insects,
      and ectopic expression of both the Drosophila and the mouse gene leads to the
      induction of ectopic eyes in Drosophila, which suggested to us that Pax 6 might
      be a universal master control gene for eye morphogenesis. Here, we report the
      reciprocal experiment in which the RNAs of the Drosophila Pax 6 homologs, eyeless
      and twin of eyeless, are transferred into a vertebrate embryo; i.e., early
      Xenopus embryos at the 2- and 16-cell stages. In both cases, ectopic eye
      structures are formed. To understand the genetic program specifying eye
      morphogenesis, we have analyzed the regulatory mechanisms of Pax 6 expression
      that initiates eye development. Previously, we have demonstrated that Notch
      signaling regulates the expression of eyeless and twin of eyeless in Drosophila.
      Here, we show that in Xenopus, activation of Notch signaling also induces eye
      related gene expression, including Pax 6, in isolated animal caps. In Xenopus
      embryos, the activation of Notch signaling causes eye duplications and proximal
      eye defects, which are also induced by overexpression of eyeless and twin of
      eyeless. These findings indicate that the gene regulatory cascade is similar in
      vertebrates and invertebrates.

PMID- 11842184
TI  - Soybean ENOD40 encodes two peptides that bind to sucrose synthase.
AB  - ENOD40 is expressed at an early stage in root nodule organogenesis in legumes.
      Identification of ENOD40 homologs in nonleguminous plants suggests that this gene
      may have a more general biological function. In vitro translation of soybean
      ENOD40 mRNA in wheat germ extracts revealed that the conserved nucleotide
      sequence at the 5' end (region I) encodes two peptides of 12 and 24 aa residues
      (peptides A and B). These peptides are synthesized de novo from very short,
      overlapping ORFs. Appropriate ORFs are present in all legume ENOD40s studied thus
      far. In this case small peptides are directly translated from polycistronic
      eukaryotic mRNA. The 24-aa peptide B was detected in nodules by Western blotting.
      Both peptides specifically bind to the same 93-kDa protein, which was affinity
      purified from soybean nodules. Using peptide mass fingerprinting, we identified
      this binding protein as nodulin 100, which is a subunit of sucrose synthase.
      Based on our data we suggest that ENOD40 peptides are involved in the control of
      sucrose use in nitrogen-fixing nodules.

PMID- 11842185
TI  - A dynamic model of the type-2 inositol trisphosphate receptor.
AB  - The dynamic properties of the inositol (1,4,5)-trisphosphate (IP(3)) receptor are
      crucial for the control of intracellular Ca(2+), including the generation of
      Ca(2+) oscillations and waves. However, many models of this receptor do not agree
      with recent experimental data on the dynamic responses of the receptor. We
      construct a model of the IP(3) receptor and fit the model to dynamic and steady
      state experimental data from type-2 IP(3) receptors. Our results indicate that,
      (i) Ca(2+) binds to the receptor using saturating, not mass-action, kinetics;
      (ii) Ca(2+) decreases the rate of IP(3) binding while simultaneously increasing
      the steady-state sensitivity of the receptor to IP(3); (iii) the rate of Ca(2+)
      induced receptor activation increases with Ca(2+) and is faster than Ca(2+)
      induced receptor inactivation; and (iv) IP(3) receptors are sequentially
      activated and inactivated by Ca(2+) even when IP(3) is bound. Our results
      emphasize that measurement of steady-state properties alone is insufficient to
      characterize the functional properties of the receptor.

PMID- 11842186
TI  - Arsenite-induced Cdc25C degradation is through the KEN-box and ubiquitin
      proteasome pathway.
AB  - Arsenite is a known human carcinogen that induces tumorigenesis through either a
      genotoxic or an epigenetic mechanism. In this study, the effect of arsenite on
      cell cycle regulation and the mechanisms that contribute to this effect were
      investigated. Treatment of the cells with arsenite suppressed cell proliferation
      and reduced cell viability in a dose- or time-dependent manner. Analysis of cell
      cycle profile and cell cycle regulatory proteins indicated that arsenite arrested
      the cell cycle at G(2)/M phase, partially through induction of cell division
      cycle 25 (Cdc25) isoform C (Cdc25C) degradation via ubiquitin-proteasome
      pathways. Mutation of the putative KEN box within the region 151 to 157 of human
      Cdc25C or treatment of the cells with a peptide competitor encompassing the KEN
      box partially inhibited arsenite-induced ubiquitination of Cdc25C. Thus, these
      results indicate that the regulated ubiquitination of Cdc25C may be involved in
      the arsenite-induced proteolytic down-regulation of Cdc25C activity in the G(2)/M
      phase of the cell cycle and suggest a link between cell cycle and the
      carcinogenic effects of arsenite.

PMID- 11842187
TI  - RNA hairpin-folding kinetics.
AB  - Based on the complete ensemble of hairpin conformations, a statistical mechanical
      model that combines the eigenvalue solutions of the rate matrix and the free
      energy landscapes has been able to predict the temperature-dependent folding
      rate, kinetic intermediates, and folding pathways for hairpin-forming RNA
      sequences. At temperatures higher than a "glass transition" temperature, T(g),
      the eigenvalues show a distinct time separation, and the rate-limiting step is a
      two-state single exponential process determined by the slowest eigenmode. At
      temperatures lower than T(g), no distinct time separation exists for the
      eigenvalues, hence multiple (slow) eigenmodes contribute to the rate-determining
      processes, and the folding involves the trapping and detrapping of kinetic
      intermediates. For a 21-nt sequence we studied, T(g) is lower than the transition
      temperature, T(m), for thermodynamic equilibrium folding. For T > T(m), starting
      from the native state, the chain undergoes a biphasic unfolding transition: a
      preequilibrated quasi-equilibrium macrostate is formed followed by a rate
      limiting two-state transition from the macrostate to the unfolded state. For T(g)
      < T < T(m), the chain undergoes a two-state on-pathway folding transition, at
      which a nucleus is formed by the base stacks close to the loop region before a
      rapid assembly of the whole hairpin structure. For T < T(g), the multistate
      kinetics involve kinetic trapping, causing the roll-over behavior in the rate
      temperature Arrhenius plot. The complex kinetic behaviors of RNA hairpins may be
      a paradigm for the folding kinetics of large RNAs.

PMID- 11842188
TI  - Resistance to Ralstonia solanacearum in Arabidopsis thaliana is conferred by the
      recessive RRS1-R gene, a member of a novel family of resistance genes.
AB  - The identification of two Arabidopsis thaliana genes involved in determining
      recessive resistance to several strains of the causal agent of bacterial wilt,
      Ralstonia solanacearum, is reported. Dominant (RRS1-S) and recessive (RRS1-R)
      alleles from susceptible and resistant accessions encode highly similar predicted
      proteins differing in length and which present a novel structure combining
      domains found in plant Toll-IL-1 receptor-nucleotide binding site-leucin-rich
      repeat resistance proteins and a WRKY motif characteristic of some plant
      transcriptional factors. Although genetically defined as a recessive allele, RRS1
      R behaves as a dominant resistance gene in transgenic plants. Sequence analysis
      of the RRS1 genes present in two homozygous intragenic recombinant lines
      indicates that several domains of RRS1-R are essential for its resistance
      function. Additionally, RRS1-R-mediated resistance is partially salicylic acid-
      and NDR1-dependent, suggesting the existence of similar signaling pathways to
      those controlled by resistance genes in specific resistance.

PMID- 11842189
TI  - Human DINB1-encoded DNA polymerase kappa is a promiscuous extender of mispaired
      primer termini.
AB  - Both in yeast and humans, DNA polymerase (Pol) (eta) functions in the error-free
      replication of UV-damaged DNA, and Pol(eta) has the unique ability to efficiently
      replicate through a cis-syn thymine-thymine (T-T) dimer by inserting two As
      opposite the two Ts of the dimer. Although human DINB1-encoded Pol(kappa) belongs
      to the same protein family as Pol(eta), Pol(kappa) shows no ability to bypass
      this DNA lesion and its biological function has remained unclear. Here, we
      examine Pol(kappa) for its ability to extend from primer-terminal mispairs
      opposite nondamaged and damaged DNA templates. We find that Pol(kappa) is a
      promiscuous extender of primer-terminal mispairs opposite nondamaged DNA
      templates, and interestingly, it is also very efficient at extending from a G
      opposite the 3'T of a T-T dimer. These observations provide biochemical evidence
      for a role of Pol(kappa) in the extension of mismatched base pairs during normal
      DNA replication, and in addition, they implicate Pol(kappa) in the mutagenic
      bypass of T-T dimers. In its proficient mismatch extension ability, Pol(kappa) is
      more similar to the unrelated DNA polymerase zeta than it is to the
      phylogenetically related Pol(eta) or Pol(iota). Thus, in humans, Pol(kappa) would
      compete with Pol(zeta) for the extension of mismatched base pairs on damaged and
      undamaged DNAs.

PMID- 11842190
TI  - Large extinctions in an evolutionary model: the role of innovation and keystone
      species.
AB  - The causes of major and rapid transitions observed in biological macroevolution
      as well as in the evolution of social systems are a subject of much debate. Here
      we identify the proximate causes of crashes and recoveries that arise dynamically
      in a model system in which populations of (molecular) species coevolve with their
      network of chemical interactions. Crashes are events that involve the rapid
      extinction of many species, and recoveries the assimilation of new ones. These
      are analyzed and classified in terms of the structural properties of the network.
      We find that in the absence of large external perturbation, "innovation" is a
      major cause of large extinctions and the prime cause of recoveries. Another major
      cause of crashes is the extinction of a "keystone species." Different classes of
      causes produce crashes of different characteristic sizes.

PMID- 11842191
TI  - Engineering gene expression and protein synthesis by modulation of nuclear shape.
AB  - The current understanding of the relationships between cell shape, intracellular
      forces and signaling, nuclear shape and organization, and gene expression is in
      its infancy. Here we introduce a method for investigating gene-specific responses
      in individual cells with controlled nuclear shape and projected area. The shape
      of the nuclei of primary osteogenic cells were controlled on microfabricated
      substrata with regiospecific chemistry by confining attachment and spreading of
      isolated cells on adhesive islands. Gene expression and protein synthesis were
      altered by changing nuclear shape. Collagen I synthesis correlated directly with
      cell shape and nuclear shape index (NSI), where intermediate values of nuclear
      distension (6 < NSI < 8) promoted maximum synthesis. Osteocalcin mRNA, a bone
      specific differentiation marker, was observed intracellularly by using reverse
      transcription in situ PCR at 4 days in cells constrained by the pattern and not
      detected in unconstrained cells of similar projected area, but different NSI. Our
      data supports the concept of gene expression and protein synthesis based on
      optimal distortion of the nucleus, possibly altering transcription factor
      affinity for DNA, transport to the nucleus, or nuclear matrix organization. The
      combination of microfabricated surfaces, reverse transcription in situ PCR, and
      NSI measurement is an excellent system to study how transcription factors, the
      nuclear matrix, and the cytoskeleton interact to control gene expression and may
      be useful for studying a wide variety of other cell shape/gene expression
      relationships.

PMID- 11842194
TI  - Sensitivity to Alternaria alternata toxin in citrus because of altered
      mitochondrial RNA processing.
AB  - Specificity in the interaction between rough lemon (Citrus jambhiri Lush.) and
      the fungal pathogen Alternaria alternata rough lemon pathotype is determined by a
      host-selective toxin, ACR-toxin. Mitochondria from rough lemon are sensitive to
      ACR-toxin whereas mitochondria from resistant plants, including other citrus
      species, are resistant. We have identified a C. jambhiri mitochondrial DNA
      sequence, designated ACRS (ACR-toxin sensitivity gene), that confers toxin
      sensitivity to Escherichia coli. ACRS is located in the group II intron of the
      mitochondrial tRNA-Ala and is translated into a SDS-resistant oligomeric protein
      in C. jambhiri mitochondria but is not translated in the toxin-insensitive
      mitochondria. ACRS is present in the mitochondrial genome of both toxin-sensitive
      and -insensitive citrus. However, in mitochondria of toxin-insensitive plants,
      the transcripts from ACRS are shorter than those in mitochondria of sensitive
      plants. These results demonstrate that sensitivity to ACR-toxin and hence
      specificity of the interaction between A. alternata rough lemon pathotype and C.
      jambhiri is due to differential posttranscriptional processing of a mitochondrial
      gene.

PMID- 11842193
TI  - Discrimination of MHC-derived odors by untrained mice is consistent with
      divergence in peptide-binding region residues.
AB  - Genes of the major histocompatibility complex (MHC) play a central role in immune
      recognition, yet they also influence the odor of individuals. Mice can be trained
      to distinguish odors mediated by classical MHC loci; however, training can
      introduce confounding behavioral artifacts. This study demonstrates that mice can
      distinguish some, but not all, naturally occurring allelic variants at classical
      MHC loci without prior training. This result suggests that MHC-disassortative
      mating preferences might operate by means of small MHC-based odor differences,
      and could therefore contribute to diversifying selection acting on MHC loci. Here
      we show that odors of two MHC mutant mouse strains (bm1 and bm3) can be
      distinguished, even after genetic background is controlled by intercrossing
      strains. These two strains differ by five amino acids, three of which are
      predicted to chemically contact peptides bound to the peptide-binding region
      (PBR), the site of antigen presentation for T cell recognition. However, the
      odors of neither bm1 nor bm3 were distinguished from their parental B6 haplotype
      after randomizing genomic background, despite discrimination of pure-bred B6 and
      bm1 strain odors. These combined results suggest that (i) there may be an MHC
      odor discrimination threshold based on divergence in PBR residues, providing a
      more logical pattern of MHC-based odor discrimination than found in previous
      training studies, where discrimination ability was not correlated with PBR
      divergence; and (ii) additional (non-MHC) mutations that influence odor have
      accumulated in these strains during the 100 generations of divergence between
      pure B6 and bm1 strains.

PMID- 11842195
TI  - Brain activity in ventromedial prefrontal cortex correlates with individual
      differences in negative affect.
AB  - Individuals differ in the extent to which they experience negative mood states
      over time. To explore the relationship between individual differences in negative
      affect (NA) and brain activity, we asked healthy subjects participating in
      positron-emission tomography scans to rate the extent to which they had
      experienced NA terms during the month before scanning. In two independent samples
      of subjects, resting regional cerebral blood flow within the ventromedial
      prefrontal cortex (VMPFC) correlated with ratings of NA. The finding converges
      with recent evidence implicating the VMPFC in emotional and autonomic processing.
      Moreover, it demonstrates that variability in basal VMPFC activity across
      subjects is related to individual differences in subjective emotional experience.

PMID- 11842197
TI  - Fabrication of aligned microstructures with a single elastomeric stamp.
AB  - The fabrication of complex patterns of aligned microstructures has required the
      use of multiple applications of lithography. Here we describe an approach for
      microfabrication that encodes the two-dimensional spatial information of several
      photomasks onto a single elastomeric stamp by mapping each photomask onto
      distinct heights on the surface of the stamp. Pressing the stamp against a
      surface collapses the topography of the stamp such that each recessed layer
      contacts the surface in stepwise sequence; the greater the applied pressure, the
      larger the area of the stamp that contacts the surface. After contact of each new
      layer with the surface, we use techniques of soft lithography (microcontact
      printing, microfluidics, and patterning through membranes) to pattern the
      surfaces that contact the stamp and those that do not with inorganic, organic, or
      living materials. Microfabrication through the use of multilevel stamps provides
      a promising alternative to conventional lithography for the construction of
      multicomponent, aligned surfaces; these structures may find use as components of
      microfluidic devices or biological patterns.

PMID- 11842196
TI  - Targeting protein inactivation through an oligomerization chain reaction.
AB  - A general strategy for inactivation of target proteins is presented, which we
      have termed "oligomerization chain reaction." This technique is based on the
      fusion of the self-associating coiled-coil (CC) domain of the nuclear factor
      promyelocytic leukemia (PML) to target proteins that are able to self-associate
      naturally. Oligomerization through the CC region of promyelocytic leukemia, and
      through the natural self-associating domain, triggers the oligomerization chain
      reaction, leading to formation of large molecular weight complexes and functional
      inactivation of the target. As a test case, we have chosen the oncosuppressor
      p53, naturally occurring as a tetramer. Fusion of the CC to p53 leads to
      formation of stable high molecular weight complexes-as shown by size exclusion
      chromatography-to which wild-type p53 is recruited with high efficiency. CC-p53
      chimeras delocalize wild-type p53 to the cytoplasm and inhibit its
      transcriptional regulatory properties, resulting in a loss of p53 function. We
      propose that this strategy may be of general application to self-associating
      factors and represent a complementary approach to currently used functional
      inactivation-based strategies.

PMID- 11842198
TI  - Topping off: a mechanism of first-male sperm precedence in a vertebrate.
AB  - Competition among the sperm of rival males is an important evolutionary
      phenomenon in many organisms. Yet, despite extensive research on sperm
      competition in some vertebrate taxa, very little progress has been made on this
      topic in amphibians. Urodele amphibians (newts and salamanders) are of particular
      interest to theories of sperm competition because most urodele females--in
      contrast to other vertebrate females--control the transfer of sperm from the
      male. Here we present a molecular study of sperm precedence and storage patterns
      in the rough-skinned newt (Taricha granulosa). First, we used microsatellite
      markers to show that female newts typically use sperm from 1-3 males under
      natural and seminatural conditions. Second, we mated experimental females
      sequentially to two males and collected fertilized eggs in a temporal series.
      Patterns of paternity were consistent with first-male sperm precedence and
      complete mixing of sperm within the female. This simple pattern of sperm usage,
      best described as "topping off," is consistent with the expectation from sexual
      conflict theory that free female choice before insemination eliminates selective
      pressures for the evolution of complex patterns of paternity manipulation
      involving cryptic female choice.

PMID- 11842199
TI  - Pattern formation by a cell surface-associated morphogen in Myxococcus xanthus.
AB  - In response to starvation, an unstructured population of identical Myxococcus
      xanthus cells rearranges into an asymmetric, stable pattern of multicellular
      fruiting bodies. Central to this pattern formation process are changes in
      organized cell movements from swarming to aggregation. Aggregation is induced by
      the cell surface-associated C-signal. To understand how aggregation is
      accomplished, we have analyzed how C-signal modulates cell behavior. We show that
      C-signal induces a motility response that includes increases in transient gliding
      speeds and in the duration of gliding intervals and decreases in stop and
      reversal frequencies. This response results in a switch in cell behavior from an
      oscillatory to a unidirectional type of behavior in which the net-distance
      traveled by a cell per minute is increased. We propose that the C-signal
      dependent regulation of the reversal frequency is essential for aggregation and
      that the remaining C-signal-dependent changes in motility parameters contribute
      to aggregation by increasing the net-distance traveled by starving cells per
      minute. In our model for symmetry-breaking and aggregation, C-signal transmission
      is a local event involving direct contacts between cells that results in a global
      organization of cells. This pattern formation mechanism does not require a
      diffusible substance or other actions at a distance. Rather it depends on contact
      induced changes in motility behavior to direct cells appropriately

PMID- 11842200
TI  - Ubiquitin-dependent mechanism regulates rapid turnover of AU-rich cytokine mRNAs.
AB  - An AU rich element (ARE) in the 3' noncoding region promotes the rapid
      degradation of mammalian cytokine and proto-oncogene mRNAs, such as tumor
      necrosis factor-alpha, granulocyte-macrophage colony-stimulating factor (GM-CSF)
      and c-fos. Destabilization of ARE-mRNAs involves the association of ARE-binding
      proteins tristetraprolin or AUF1 and proteasome activity, of which the latter has
      not been characterized. Here, we show that the stability of a model short-lived
      mRNA containing the GM-CSF ARE was regulated by the level of ubiquitin
      conjugating activity in the cell, which links ARE-mRNA decay to proteasome
      activity. Increased expression of a cytokine-inducible deubiquitinating protein
      (DUB) that impairs addition of ubiquitin to proteins fully blocked ARE-mRNA
      decay, whereas increased expression of a DUB that promotes ubiquitin addition to
      proteins strongly accelerated ARE-mRNA decay. ARE-mRNA turnover was found to be
      activated by the ubiquitin-addition reaction and blocked by the ubiquitin-removal
      reaction. Saturation of the ARE-mRNA decay machinery by high levels of ARE-mRNA,
      which is well established but not understood, was found to be relieved by
      increased expression of a DUB that promotes ubiquitin addition to proteins.
      Finally, inhibition of proteasome activity also blocked accelerated ARE-mRNA
      decay that is mediated by increased ubiquitin recycling. These results
      demonstrate that both ubiquitinating activity and proteasome activity are
      essential for rapid turnover of a model cytokine ARE-mRNA containing the GM-CSF
      ARE.

PMID- 11842201
TI  - Intracellular distribution of viral gene products regulates a complex mechanism
      of cauliflower mosaic virus acquisition by its aphid vector.
AB  - Interactions between Cauliflower mosaic virus (CaMV) and its aphid vector are
      regulated by the viral protein P2, which binds to the aphid stylets, and protein
      P3, which bridges P2 and virions. By using baculovirus expression of P2 and P3,
      electron microscopy, surface plasmon resonance, affinity chromatography, and
      transmission assays, we demonstrate that P3 must be previously bound to virions
      in order that attachment to P2 will allow aphid transmission of CaMV. We also
      show that a P2:P3 complex exists in the absence of virions but is nonfunctional
      in transmission. Hence, unlike P2, P3 and virions cannot be sequentially acquired
      by the vector. Immunogold labeling revealed the predominance of spatially
      separated P2:P3 and P3:virion complexes in infected plant cells. This specific
      distribution indicates that the transmissible complex, P2:P3:virion, does not
      form primarily in infected plants but in aphids. A model, describing the
      regulating role of P3 in the formation of the transmissible CaMV complex in
      planta and during acquisition by aphids, is presented, and its consequences are
      discussed.

PMID- 11842202
TI  - Developing nodes of Ranvier are defined by ankyrin-G clustering and are
      independent of paranodal axoglial adhesion.
AB  - Nodes of Ranvier are excitable regions of axonal membranes highly enriched in
      voltage-gated sodium channels that propagate action potentials. The mechanism of
      protein clustering at nodes has been a source of controversy. In this study,
      developmental analysis of nodes of Ranvier in optic nerve axons reveals that
      early node intermediates are defined by ankyrin-G. Other node components,
      including beta IV spectrin, voltage-gated sodium channels, and the L1 cell
      adhesion molecule neurofascin, are subsequently recruited to sites of ankyrin-G
      clustering. The role of intact paranodes in protein clustering was examined in
      the dysmyelinating mouse mutant jimpy. Jimpy mice do not have intact paranodal
      axoglial contacts, which is indicated by a complete lack of neurexin/contactin
      associated protein/paranodin clustering in paranodes. In the absence of intact
      paranodes, ankyrin-G was still able to cluster, although fewer ankyrin clusters
      were seen in jimpy optic nerves than in wild-type optic nerves. Recruitment of
      Na(v)1.2, Na(v)1.6, beta IV spectrin, and neurofascin to sites of ankyrin-G
      clustering is unimpaired in jimpy mice, indicating that node formation occurs
      independent of intact paranodal axoglial contacts.

PMID- 11842203
TI  - Increased pollen flow counteracts fragmentation in a tropical dry forest: an
      example from Swietenia humilis Zuccarini.
AB  - Habitat destruction and the resultant fragmentation of the remaining forest are a
      common phenomenon in the tropics. Most investigations emphasize the potential
      dangers of fragmentation in isolating patches of forest and exposing populations
      to loss of species diversity through founder effects, genetic drift, inbreeding,
      and restricted gene flow. However, a limited number of studies have shown that
      gene flow may be extensive in tropical trees, suggesting that it may occur
      between forest fragments and also "isolated" remnant trees. There is an urgent
      need to quantify pollen flow within and between forest fragments to test the
      veracity of such views and determine the genetic value of such fragments for in
      situ conservation. Microsatellite markers are used to genotype individuals of
      Swietenia humilis from a highly fragmented forest mosaic to directly quantify
      pollen-mediated gene flow. Distances of pollen flow more than 10 times greater
      than previously reported were detected. Our results show that some tropical
      angiosperm tree species may be much more adaptable and resilient to habitat
      destruction and fragmentation than previously considered. The description of many
      remnant trees as isolated or "living dead" may be more a conditioning of human
      perception than a true reflection of their potential conservation value.

PMID- 11842204
TI  - Intrinsic flexibility and gating mechanism of the potassium channel KcsA.
AB  - The gating mechanism of the potassium channel KcsA was studied by normal mode
      analysis. The results provided an atomic description of the locations of the
      pivot points and the motional features of key structural elements in the gating
      process. Two pivot points were found in the motions of the inner TM2 helical
      bundle that directly modulate the size of the central channel pore. One point is
      an intrasubunit hinge point that sharply divides the structural flexibility
      between the more rigid selectivity filter and the more mobile peripheral
      transmembrane helices. Such a division is vital for KcsA because it permits the
      large-scale motions of transmembrane helices required for the gating and, in the
      meantime, maintains the rigidity of the filter region essential for the
      selectivity. The other pivot point is an intersubunit one at which all four TM2
      helices are bundled together. During the gating process, each TM2 helix undergoes
      a lever-like swinging motion pivoting on the intrasubunit hinge, and the entire
      TM2 bundle undergoes a concerted rotational motion around the central channel
      axis constrained around the intersubunit bundle point. This series of motions
      leads to a dramatic enlargement of the intracellular gate without loosening up
      the structural integrity.

PMID- 11842205
TI  - Structure of adenylylsulfate reductase from the hyperthermophilic Archaeoglobus
      fulgidus at 1.6-A resolution.
AB  - The iron-sulfur flavoenzyme adenylylsulfate (adenosine 5'-phosphosulfate, APS)
      reductase catalyzes reversibly the reduction of APS to sulfite and AMP. The
      structures of APS reductase from the hyperthermophilic Archaeoglobus fulgidus in
      the two-electron reduced state and with sulfite bound to FAD are reported at 1.6-
      and 2.5- resolution, respectively. The FAD-sulfite adduct was detected after
      soaking the crystals with APS. This finding and the architecture of the active
      site strongly suggest that catalysis involves a nucleophilic attack of the N5
      atom of reduced FAD on the sulfur atom of APS. In view of the high degree of
      similarity between APS reductase and fumarate reductase especially with regard to
      the FAD-binding alpha-subunit, it is proposed that both subunits originate from a
      common ancestor resembling archaeal APS reductase. The two electrons required for
      APS reduction are transferred via two [4Fe-4S] clusters from the surface of the
      protein to FAD. The exceptionally large difference in reduction potential of
      these clusters (-60 and -500 mV) can be explained by interactions of the clusters
      with the protein matrix.

PMID- 11842206
TI  - Adeno-associated virus effectively mediates conditional gene modification in the
      brain.
AB  - The Cre/loxP system is increasingly showing promise for investigating genes
      involved in neural function. Here, we demonstrate that in vivo modification of
      genes in the mouse brain can be accomplished in a spatial- and temporal-specific
      manner by targeted delivery of an adeno-associated virus (AAV) encoding a green
      fluorescent protein/Cre recombinase (GFP/Cre) fusion protein. By using a reporter
      mouse, in which Cre recombinase activates beta-galactosidase expression, we
      demonstrate long-term recombination of neurons in the hippocampus, striatum, and
      septum as early as 7 days after stereotaxic injection of virus. Recombined cells
      were observed for at least 6 months postinjection without evidence of cell loss
      or neural damage. AAV-mediated delivery of GFP/Cre provides a valuable approach
      to alter the mouse genome, as AAV delivers genes efficiently to neurons with low
      toxicity. This approach will greatly facilitate the study of genetic
      modifications in the mouse brain.

PMID- 11842208
TI  - The first linkage disequilibrium (LD) maps: delineation of hot and cold blocks by
      diplotype analysis.
AB  - Linkage disequilibrium (LD) provides information about positional cloning,
      linkage, and evolution that cannot be inferred from other evidence, even when a
      correct sequence and a linkage map based on more than a handful of families
      become available. We present theory to construct an LD map for which distances
      are additive and population-specific maps are expected to be approximately
      proportional. For this purpose, there is only a modest difference in relative
      efficiency of haplotypes and diplotypes: resolving the latter into 2-locus
      haplotypes has significant cost or error and increases information by about 50%.
      LD maps for a cold spot in 19p13.3 and a more typical region in 3q21 are
      optimized by interval estimates. For a random sample and trustworthy map the
      value of LD at large distance can be predicted reliably from information over a
      small distance and does not depend on the evolutionary variance unless the sample
      size approaches the population size. Values of the association probability that
      can be distinguished from the value at large distance are determined not by
      population size but by time since a critical bottleneck. In these examples,
      omission of markers with significant Hardy-Weinberg disequilibrium does not
      improve the map, and widely discrepant draft sequences have similar estimates of
      the genetic parameters. The LD cold spot in 19p13.3 gives an unusually high
      estimate of time, supporting an argument that this relationship is general. As
      predicted for a region with ancient haplotypes or uniformly high recombination,
      there is no clear evidence of LD clustering. On the contrary, the 3q21 region is
      resolved into alternating blocks of stable and decreasing LD, as expected from
      crossover clustering. Construction of a genomewide LD map requires data not yet
      available, which may be complemented but not replaced by a catalog of haplotypes.

PMID- 11842207
TI  - 2',3'-Cyclic nucleotide 3'-phosphodiesterase: a membrane-bound, microtubule
      associated protein and membrane anchor for tubulin.
AB  - 2',3'-Cyclic nucleotide-3'-phosphodiesterase (CNP) is firmly associated with
      tubulin from brain tissue and FRTL-5 thyroid cells as demonstrated by
      copolymerization with microtubules through several warm/cold cycles, the presence
      of CNP activity in purified tubulin preparations, and identical behavior during
      various extraction procedures. CNP acts as a microtubule-associated protein in
      promoting microtubule assembly at low mole ratios. This activity resides in the C
      terminus of the enzyme, which, by itself, promotes microtubule assembly at higher
      mole ratios. Phosphorylation of CNP interferes with its assembly-promoting
      activity, as does deletion of the C terminus, which leads to abnormal microtubule
      distribution in the cell. Submembranous colocalization of the proteins and CNP
      dependent microtubule organization suggest that CNP is a membrane-bound
      microtubule-associated protein that can link tubulin to membranes and may
      regulate cytoplasmic microtubule distribution.

PMID- 11842209
TI  - HOX genes in the sepiolid squid Euprymna scolopes: implications for the evolution
      of complex body plans.
AB  - Molluscs display a rich diversity of body plans ranging from the wormlike
      appearance of aplacophorans to the complex body plan of the cephalopods with
      highly developed sensory organs, a complex central nervous system, and cognitive
      abilities unrivaled among the invertebrates. The aim of the current study is to
      define molecular parameters relevant to the developmental evolution of
      cephalopods by using the sepiolid squid Euprymna scolopes as a model system.
      Using PCR-based approaches, we identified one anterior, one paralog group 3, five
      central, and two posterior group Hox genes. The deduced homeodomain sequences of
      the E. scolopes Hox cluster genes are most similar to known annelid, brachiopod,
      and nemertean Hox gene homeodomain sequences. Our results are consistent with the
      presence of a single Hox gene cluster in cephalopods. Our data also corroborate
      the proposed existence of a differentiated Hox gene cluster in the last common
      ancestor of Bilaterians. Furthermore, our phylogenetic analysis and in particular
      the identification of Post-1 and Post-2 homologs support the Lophotrochozoan
      clade.

PMID- 11842210
TI  - Laser capture microdissection analysis of gene expression in macrophages from
      atherosclerotic lesions of apolipoprotein E-deficient mice.
AB  - Macrophage foam cells are integral in the development of atherosclerotic lesions.
      Gene expression analysis of lesional macrophage foam cells is complicated by the
      cellular heterogeneity of atherosclerotic plaque and the presence of lesions of
      various degrees of severity. To overcome these limitations, we tested the ability
      of laser capture microdissection (LCM) and real-time quantitative reverse
      transcription PCR to selectively analyze RNA from lesional macrophages of
      apolipoprotein E (apoE)-deficient mice. Proximal aortic tissue sections were
      immunostained for macrophagespecific CD68/macrosialin by a rapid (approximately
      15-min) protocol. Alternating sections from each animal were used to isolate RNA
      either from entire sections (analogous to isolation from whole tissue) or by LCM
      selection of CD68-positive cells. We measured the mRNA levels of CD68, a
      macrophage-specific marker, alpha-actin, a smooth muscle cell marker, and
      cyclophilin A, a control gene. Compared with whole sections, CD68 mRNA levels
      were greatly enriched (33.6-fold) in the laser-captured lesional macrophages. In
      contrast to whole sections, LCM-derived RNA had undetectable levels of alpha
      actin. To illustrate the ability of this method to measure changes in lesional
      macrophage gene expression, we injected 100 microg of lipopolysaccharide i.p.
      into apoE-deficient mice and detected in laser-captured lesional macrophages
      increased mRNA expression for vascular cell adhesion molecule-1, intercellular
      cell adhesion molecule-1, and monocyte chemoattractant protein-1 (11.9-, 32.5-,
      and 31.0-fold, respectively). By selectively enriching foam cell RNA, LCM
      provides a powerful approach to study the in situ expression and regulation of
      atherosclerosis-related genes. This approach will allow the study of macrophage
      gene expression under various conditions of plaque formation, regression, and
      response to genetic and environmental perturbations.

PMID- 11842211
TI  - WASp verprolin homology, cofilin homology, and acidic region domain-mediated
      actin polymerization is required for T cell development.
AB  - All members of the Wiskott-Aldrich syndrome protein (WASp) family contain a
      carboxyl-terminal verprolin homology, cofilin homology, and acidic region (VCA)
      domain that binds and activates the Arp2/3 complex, thereby linking these
      proteins to the induction of actin polymerization. Although the VCA domain imbues
      WASp and other WASp family members with the capacity to modulate cytoskeletal
      organization, little is known about the impact of this domain activity on
      lymphoid cell function. Here we demonstrate that T cell-restricted expression of
      VCA domain-deleted WASp (WASpdeltaVCA) in WAS(-/-) mice engenders a severe early
      block in T lymphopoiesis associated with impaired T cell antigen receptor
      alphabeta expression and a consequent failure to generate single-positive CD4(+)
      and CD8(+) T cells. These latter defects, which are not observed in WAS(-/-)
      mice, are associated with impaired induction of cellular actin polymerization and
      a failure in the terminal differentiation of double-negative thymocytes. These
      findings indicate that WASp family proteins play an essential role in modulating
      the signaling events required for early thymocyte development and reveal their
      capacity to subserve this role to depend on VCA domain-mediated actin
      polymerization.

PMID- 11842212
TI  - Functional implications of the localization and activity of acid-sensitive
      channels in rat peripheral nervous system.
AB  - Acid-sensitive ion channels (ASIC) are proton-gated ion channels expressed in
      neurons of the mammalian central and peripheral nervous systems. The functional
      role of these channels is still uncertain, but they have been proposed to
      constitute mechanoreceptors and/or nociceptors. We have raised specific
      antibodies for ASIC1, ASIC2, ASIC3, and ASIC4 to examine the distribution of
      these proteins in neurons from dorsal root ganglia (DRG) and to determine their
      subcellular localization. Western blot analysis demonstrates that all four ASIC
      proteins are expressed in DRG and sciatic nerve. Immunohistochemical experiments
      and functional measurements of unitary currents from the ASICs with the patch
      clamp technique indicate that ASIC1 localizes to the plasma membrane of small-,
      medium-, and large-diameter cells, whereas ASIC2 and ASIC3 are preferentially in
      medium to large cells. Neurons coexpressing ASIC2 and ASIC3 form predominantly
      heteromeric ASIC2-3 channels. Two spliced forms, ASIC2a and ASIC2b, colocalize in
      the same population of DRG neurons. Within cells, the ASICs are present mainly on
      the plasma membrane of the soma and cellular processes. Functional studies
      indicate that the pH sensitivity for inactivation of ASIC1 is much higher than
      the one for activation; hence, increases in proton concentration will inactivate
      the channel. These functional properties and localization in DRG have profound
      implications for the putative functional roles of ASICs in the nervous system.

PMID- 11842213
TI  - Characterization of the Met326Ile variant of phosphatidylinositol 3-kinase
      p85alpha.
AB  - Phosphatidylinositol 3-kinase is a key step in the metabolic actions of insulin.
      Two amino acid substitutions have been identified in the gene for the regulatory
      subunit of human p85alpha, Met-326Ile, and Asn-330Asp, and the former has been
      associated with alterations in glucose/insulin homeostasis. When the four human
      p85alpha proteins were expressed in yeast, a 27% decrease occurred in the level
      of protein expression of p85alpha(Ile/Asp) (P = 0.03) and a 43% decrease in
      p85alpha(Ile/Asn) (P = 0.08) as compared with p85alpha(Met/Asp). Both
      p85alpha(Ile/Asp) and p85alpha(Ile/Asn) also exhibited increased binding to
      phospho-insulin receptor substrate-1 by 41% and 83%, respectively (P < 0.001), as
      compared with p85alpha(Met/Asp). The expression of p85alpha(Ile) was also
      slightly decreased and the binding to insulin receptor substrate-1 slightly
      increased in brown preadipocytes derived from p85alpha knockout mice. Both
      p85alpha(Met) and p85alpha(Ile) had similar effects on AKT activity and were able
      to reconstitute differentiation of the preadipocytes, although the triglyceride
      concentration in fully differentiated adipocytes and insulin-stimulated 2
      deoxyglucose uptake were slightly lower than in adipocytes expressing
      p85alpha(Met). Thus, the Met-326Ile variant of p85alpha is functional for
      intracellular signaling and adipocyte differentiation but has small alterations
      in protein expression and activity that could play a role in modifying insulin
      action.

PMID- 11842215
TI  - Crosstalk among stress responses in plants: pathogen defense overrides UV
      protection through an inversely regulated ACE/ACE type of light-responsive gene
      promoter unit.
AB  - Plants often have to cope with two or more environmental hazards simultaneously.
      Such coincidences require instantaneous decisions on relative severity and
      consequential crosstalk between the respective signaling cascades. Among the
      frequently encountered threats are pathogen infections and UV irradiation, both
      of which trigger specifically targeted defense responses by means of changes in
      gene transcription rates. In Petroselinum crispum, pathogen defense has been
      shown to be associated with extensive metabolic reprogramming, including strong
      repression of the UV-protective flavonoid biosynthetic pathway. Here we show that
      one of the involved genes, encoding acyl-CoA oxidase, responds positively to UV
      light and negatively to a pathogen-derived elicitor through an inversely
      regulated promoter unit consisting of two almost identical ACGT-containing
      elements (ACEs). This unit, when either introduced into an unrelated promoter or
      generated by mutation of a differently composed unit, confers the same type of
      response pattern on the recipient genes, confirming its general functionality at
      a convergence site of two largely distinct signaling pathways. Similarly large,
      rapid, and partly inverse effects of UV light and elicitor were observed for
      several mRNAs encoding common plant regulatory factors (CPRFs) that exhibit
      distinct dimerization and DNA-binding properties. This striking coincidence
      suggests a major role of common plant regulatory factors in mediating the
      apparent switch in the function of ACGT-containing elements from positive UV
      light to negative elicitor or pathogen responsiveness.

PMID- 11842214
TI  - Alveolar epithelial type I cells contain transport proteins and transport sodium,
      supporting an active role for type I cells in regulation of lung liquid
      homeostasis.
AB  - Transport of lung liquid is essential for both normal pulmonary physiologic
      processes and for resolution of pathologic processes. The large internal surface
      area of the lung is lined by alveolar epithelial type I (TI) and type II (TII)
      cells; TI cells line >95% of this surface, TII cells <5%. Fluid transport is
      regulated by ion transport, with water movement following passively. Current
      concepts are that TII cells are the main sites of ion transport in the lung. TI
      cells have been thought to provide only passive barrier, rather than active,
      functions. Because TI cells line most of the internal surface area of the lung,
      we hypothesized that TI cells could be important in the regulation of lung liquid
      homeostasis. We measured both Na(+) and K(+) (Rb(+)) transport in TI cells
      isolated from adult rat lungs and compared the results to those of concomitant
      experiments with isolated TII cells. TI cells take up Na(+) in an amiloride
      inhibitable fashion, suggesting the presence of Na(+) channels; TI cell Na(+)
      uptake, per microgram of protein, is approximately 2.5 times that of TII cells.
      Rb(+) uptake in TI cells was approximately 3 times that in TII cells and was
      inhibited by 10(-4) M ouabain, the latter observation suggesting that TI cells
      exhibit Na(+)-, K(+)-ATPase activity. By immunocytochemical methods, TI cells
      contain all three subunits (alpha, beta, and gamma) of the epithelial sodium
      channel ENaC and two subunits of Na(+)-, K(+)-ATPase. By Western blot analysis,
      TI cells contain approximately 3 times the amount of alphaENaC/microg protein of
      TII cells. Taken together, these studies demonstrate that TI cells not only
      contain molecular machinery necessary for active ion transport, but also
      transport ions. These results modify some basic concepts about lung liquid
      transport, suggesting that TI cells may contribute significantly in maintaining
      alveolar fluid balance and in resolving airspace edema.

PMID- 11842216
TI  - Interactions between double positive thymocytes and high affinity ligands
      presented by cortical epithelial cells generate double negative thymocytes with T
      cell regulatory activity.
AB  - Previous studies on thymocyte differentiation by using reaggregate cultures (RC)
      of double positive T cell receptor (TCR) transgenic thymocytes and the thymic
      epithelial cell line ANV indicated that low concentrations of high affinity
      ligands for the TCR were efficient inducers of thymocyte maturation to CD4 single
      positive (SP) functional cells. In this study, it is demonstrated that, when high
      concentrations of high affinity ligands are used in this RC system, double
      positive (DP) cells down-modulate expression of both coreceptors and that, as a
      result, large numbers of double negative (DN) cells are generated. These DN cells
      proliferated modestly in response to stimulation by antigen, and this response
      was considerably augmented by the addition of IL-2 to the cultures. Notably,
      these antigen-stimulated DN cells produced large amounts of IL-10. When the DN
      cells generated in RC were cocultured with naive TCR transgenic T cells in the
      presence of antigen, they suppressed the proliferative response of the naive T
      cells. Thus, high affinity ligands, when presented to DP thymocytes by cortical
      thymic epithelial cells in reaggregate cultures, rather than causing deletion of
      the immature thymocytes, induce their differentiation into immunoregulatory DN
      cells, suggesting a distinct mechanism by which self tolerance may be maintained.

PMID- 11842217
TI  - The brain-derived neurotrophic factor enhances synthesis of Arc in
      synaptoneurosomes.
AB  - Protein synthesis in neurons is essential for the consolidation of memory and for
      the stabilization of activity-dependent forms of synaptic plasticity such as long
      term potentiation (LTP). Activity-dependent translation of dendritically
      localized mRNAs has been proposed to be a critical source of new proteins
      necessary for synaptic change. mRNA for the activity-regulated cytoskeletal
      protein, Arc, is transcribed during LTP and learning, and disruption of its
      translation gives rise to deficits in both. We have found that selective
      translation of Arc in a synaptoneurosomal preparation is induced by the brain
      derived neurotrophic factor, a neurotrophin that is released during high
      frequency stimulation patterns used to elicit LTP. This effect involves signaling
      through the TrkB receptor and is blocked by the N-methyl-d-aspartate-type
      glutamate receptor antagonist, MK801. The results suggest there is a synergy
      between neurotrophic and ionotropic mechanisms that may influence the specificity
      and duration of changes in synaptic efficacy at glutamatergic synapses.

PMID- 11842218
TI  - Biological water at the protein surface: dynamical solvation probed directly with
      femtosecond resolution.
AB  - Biological water at the interface of proteins is critical to their equilibrium
      structures and enzyme function and to phenomena such as molecular recognition and
      protein-protein interactions. To actually probe the dynamics of water structure
      at the surface, we must examine the protein itself, without disrupting the native
      structure, and the ultrafast elementary processes of hydration. Here we report
      direct study, with femtosecond resolution, of the dynamics of hydration at the
      surface of the enzyme protein Subtilisin Carlsberg, whose single Trp residue (Trp
      113) was used as an intrinsic biological fluorescent probe. For the protein, we
      observed two well separated dynamical solvation times, 0.8 ps and 38 ps, whereas
      in bulk water, we obtained 180 fs and 1.1 ps. We also studied a covalently bonded
      probe at a separation of approximately 7 A and observed the near disappearance of
      the 38-ps component, with solvation being practically complete in (time constant)
      1.5 ps. The degree of rigidity of the probe (anisotropy decay) and of the water
      environment (protein vs. micelle) was also studied. These results show that
      hydration at the surface is a dynamical process with two general types of
      trajectories, those that result from weak interactions with the selected surface
      site, giving rise to bulk-type solvation (approximately 1 ps), and those that
      have a stronger interaction, enough to define a rigid water structure, with a
      solvation time of 38 ps, much slower than that of the bulk. At a distance of
      approximately 7 A from the surface, essentially all trajectories are bulk-type.
      The theoretical framework for these observations is discussed.

PMID- 11842219
TI  - Low-temperature-induced accumulation of xanthophylls and its structural
      consequences in the photosynthetic membranes of the cyanobacterium
      Cylindrospermopsis raciborskii: an FTIR spectroscopic study.
AB  - The effects of the growth temperature on the lipids and carotenoids of a
      filamentous cyanobacterium, Cylindrospermopsis raciborskii, were studied., The
      relative amounts of polyunsaturated glycerolipids and myxoxanthophylls in the
      thylakoid membranes increased markedly when this cyanobacterium was grown at 25
      degrees C instead of 35 degrees C. Fourier transform infrared spectroscopy was
      used to analyze the low-temperature-induced structural alterations in the
      thylakoid membranes. Despite the higher amount of unsaturated lipids there,
      conventional analysis of the v(sym)CH(2) band (characteristic of the lipid
      disorder) revealed more tightly arranged fatty-acyl chains for the thylakoids in
      the cells grown at 25 degrees C as compared with those grown at 35 degrees C.
      This apparent controversy was resolved by a two-component analysis of the
      v(sym)CH(2) band, which demonstrated very rigid, myxoxanthophyll-related lipids
      in the thylakoid membranes. When this rigid component was excluded from the
      analysis of the thermotropic responses of the v(sym)CH(2) bands, the expected
      higher fatty-acyl disorder was observed for the thylakoids prepared from cells
      grown at 25 degrees C as compared with those grown at 35 degrees C. Both the
      carotenoid composition and this rigid component in the thylakoid membranes were
      only growth temperature-dependent; the intensity of the illuminating light during
      cultivation had no apparent effect on these parameters. We propose that, besides
      their well-known protective functions, the polar carotenoids in particular may
      have structural effects on the thylakoid membranes. These effects should be
      exerted locally--by forming protective patches, in-membrane barriers of low
      dynamics--to prevent the access of reactive radicals generated in either
      enzymatic or photosynthetic processes to sensitive spots of the membranes.

PMID- 11842220
TI  - TROSY-NMR reveals interaction between ERp57 and the tip of the calreticulin P
      domain.
AB  - The lectin chaperone calreticulin (CRT) assists the folding and quality control
      of newly synthesized glycoproteins in the endoplasmic reticulum (ER). It
      interacts with ERp57, a thiol-disulfide oxidoreductase that promotes the
      formation of disulfide bonds in glycoproteins bound by CRT. Here, we investigated
      the interaction between CRT and ERp57 by using biochemical techniques and NMR
      spectroscopy. We found that ERp57 binds to the P-domain of calreticulin, an
      independently folding domain comprising residues 189-288. Isothermal titration
      calorimetry showed that the dissociation constant of the CRT(189-288)/ERp57
      complex is (9.1 +/- 3.0) x 10(-6) M at 8 degrees C. Transverse relaxation
      optimized NMR spectroscopy provided data on the thermodynamics and kinetics of
      the complex formation and on the structure of this 66.5-kDa complex. The NMR
      measurements yielded a value of (18 +/- 5) x 10(-6) M at 20 degrees C for the
      dissociation constant and a lower limit for the first-order exchange rate
      constant of k(off) > 1,000 s(-1) at 20 degrees C. Chemical shift mapping showed
      that interactions with ERp57 occur exclusively through amino acid residues in the
      polypeptide segment 225-251 of CRT(189-288), which forms the tip of the hairpin
      structure of this domain. These results are analyzed with regard to the
      functional mechanism of the CRT/ERp57 chaperone system.

PMID- 11842221
TI  - Gonadotropin-releasing hormone neurons in the preoptic-hypothalamic region of the
      rat contain lamprey gonadotropin-releasing hormone III, mammalian luteinizing
      hormone-releasing hormone, or both peptides.
AB  - This study utilized a newly developed antiserum, specific for lamprey
      gonadotropin-releasing hormone III (l-GnRH-III), to determine the following: in
      which regions of the rat hypothalamus the neuronal perikarya producing l-GnRH-III
      are localized; and whether this peptide, known to selectively induce follicle
      stimulating hormone release, is coexpressed in neurons containing mammalian
      luteinizing hormone-releasing hormone (m-LHRH). Double-label immunocytochemistry
      was performed by using an l-GnRH-III polyclonal antiserum and an LHRH monoclonal
      antiserum. Immunopositive neurons for l-GnRH-III, m-LHRH, or neurons coexpressing
      both peptides were detected within the organum vasculosum lamina terminalis
      (OVLT) region of the preoptic area (POA). Caudal to the OVLT, l-GnRH-III-positive
      neurons were also observed dorso-medially, above the third ventricle in the
      medial POA. The m-LHRH neurons were not observed in this area. The lateral POA
      region contained neurons positive for both peptides along with single-labeled
      neurons for each peptide. Importantly, neurons that expressed l-GnRH-III, m-LHRH,
      or both peptides were also detected in the ventral regions of the rostral
      hypothalamus, dorsolateral to the borders of the supraoptic nuclei. In both of
      these latter areas, neurons containing l-GnRH-III were slightly dorsal to neurons
      containing only m-LHRH. The l-GnRH-III perikarya and fibers were eliminated by
      absorption of the primary antiserum with l-GnRH-III, but not by l-GnRH-I, chicken
      GnRH-II, or m-LHRH. These results indicate that, unlike other isoforms of GnRH
      found in the mammalian brain, l-GnRH-III neurons not only are observed in regions
      that control follicle-stimulating hormone release but also are colocalized with m
      LHRH neurons in areas primarily controlling LH release. These findings suggest an
      interrelationship between these two peptides in the control of gonadotropin
      secretion.

PMID- 11842222
TI  - Incision of DNA-protein crosslinks by UvrABC nuclease suggests a potential repair
      pathway involving nucleotide excision repair.
AB  - DNA-protein crosslinks (DPCs) arise in biological systems as a result of exposure
      to a variety of chemical and physical agents, many of which are known or
      suspected carcinogens. The biochemical pathways for the recognition and repair of
      these lesions are not well understood in part because of methodological
      difficulties in creating site-specific DPCs. Here, a strategy for obtaining site
      specific DPCs is presented, and in vitro interactions of the Escherichia coli
      nucleotide excision repair (NER) UvrABC nuclease at sites of DPCs are
      investigated. To create site-specific DPCs, the catalytic chemistry of the T4
      pyrimidine dimer glycosylase/apurinic/apyrimidinic site lyase (T4-pdg) has been
      exploited, namely, its ability to be covalently trapped to apurinic/apyrimidinic
      sites within duplex DNA under reducing conditions. Incubation of the DPCs with
      UvrABC proteins resulted in DNA incision at the 8th phosphate 5' and the 5th and
      6th phosphates 3' to the protein-adducted site, generating as a major product of
      the reaction a 12-mer DNA fragment crosslinked with the protein. The incision
      occurred only in the presence of all three protein subunits, and no incisions
      were observed in the nondamaged complementary strand. The UvrABC nuclease incises
      DPCs with a moderate efficiency. The proper assembly and catalytic function of
      the NER complex on DNA containing a covalently attached 16-kDa protein suggest
      that the NER pathway may be involved in DPC repair and that at least some subset
      of DPCs can be removed by this mechanism without prior proteolytic degradation.

PMID- 11842223
TI  - Motility initiation in herring sperm is regulated by reverse sodium-calcium
      exchange.
AB  - Sperm of the Pacific herring, Clupea pallasi, are unique in that they are
      immotile upon spawning in the environment. Herring sperm have evolved to remain
      motionless for up to several days after spawning, yet are still capable of
      fertilizing eggs. An egg chorion ligand termed "sperm motility initiation factor"
      (SMIF) induces motility in herring sperm and is required for fertilization. In
      this study, we show that SMIF induces calcium influx, sodium efflux, and a
      membrane depolarization in herring sperm. Sperm motility initiation by SMIF
      depended on decreased extracellular sodium (<350 mM) and could be induced in the
      absence of SMIF in very low sodium seawater. Motility initiation depended on > or
      =1 mM extracellular calcium. Calcium influx caused by SMIF involved both the
      opening of voltage-gated calcium channels and reverse sodium-calcium
      (Na(+)/Ca(2+)) exchange. Membrane depolarization was slightly inhibited by a
      calcium channel blocker and markedly inhibited by a Na(+)/Ca(2+) exchange
      inhibitor. Sodium efflux caused by SMIF-initiated motility was observed when
      using both extracellular and intracellular sodium probes. A Na(+)/Ca(2+) exchange
      antigen was shown to be present on the surface of the sperm, primarily over the
      midpiece, by using an antibody to the canine Na(+)/Ca(2+) exchanger. This
      antibody recognized a 120-kDa protein that comigrated with the canine myocyte
      Na(+)/Ca(2+) exchanger. Sperm of Pacific herring are now shown to use reverse
      Na(+)/Ca(2+) exchange in motility initiation. This mechanism of regulation of
      motility initiation may have evolved for both maintenance of immotility after
      spawning as well as ligand-induced motility initiation.

PMID- 11842224
TI  - The archetype STYX/dead-phosphatase complexes with a spermatid mRNA-binding
      protein and is essential for normal sperm production.
AB  - Differentiation of spermatids into spermatozoa is regulated via phosphorylated
      RNA-binding proteins that modulate the expression of stage-specific mRNAs. We
      demonstrate that the phosphoserine, -threonine or -tyrosine, interaction protein,
      Styx, complexes with a testicular RNA-binding protein and is essential for normal
      spermiogenesis. Ablation of Styx expression in mouse disrupts round and
      elongating spermatid development, resulting in a >1,000-fold decrease in
      spermatozoa production. Moreover, Styx(-/-) males are infertile because of
      structural head abnormalities in residual epididymal sperm. Immunoprecipitation
      of Styx with Crhsp-24, a phosphorylated RNA-binding protein implicated in
      translational repression of histone mRNAs, provides a strategy for regulating
      posttranscriptional gene expression.

PMID- 11842225
TI  - Top-down mass spectrometry of a 29-kDa protein for characterization of any
      posttranslational modification to within one residue.
AB  - A mass difference between the measured molecular weight of a protein and that of
      its DNA-predicted sequence indicates sequence errors and/or posttranslational
      modifications. In the top-down mass spectrometry approach, the measured molecular
      ion is dissociated, and these fragment masses are matched against those predicted
      from the protein sequence to restrict the locations of the errors/modifications.
      The proportion of the ion's interresidue bonds that are cleaved determines the
      specificity of such locations; previously, ubiquitin (76 residues) was the
      largest for which all such bonds were dissociated. Now, cleavages are achieved
      for carbonic anhydrase at 250 of the 258 interresidue locations. Cleavages of
      three spectra would define posttranslational modifications at 235 residues to
      within one residue. For 24 of the 34 possible phosphorylation sites, the
      cleavages of one spectrum would delineate exactly all -PO(3)H substitutions. This
      result has been achieved with electron-capture dissociation by minimizing the
      further cleavage of primary product ions and by denaturing the tertiary
      noncovalent bonding of the molecular ions under a variety of conditions.

PMID- 11842226
TI  - Long-term microclimatic stress causes rapid adaptive radiation of kaiABC clock
      gene family in a cyanobacterium, Nostoc linckia, from "Evolution Canyons" I and
      II, Israel.
AB  - Cyanobacteria are the only prokaryotes known thus far possessing regulation of
      physiological functions with approximate daily periodicity, or circadian rhythms,
      that are controlled by a cluster of three genes, kaiA, kaiB, and kaiC. Here we
      demonstrate considerably higher genetic polymorphism and extremely rapid
      evolution of the kaiABC gene family in a filamentous cyanobacterium, Nostoc
      linckia, permanently exposed to the acute natural environmental stress in the two
      microsite evolutionary models known as "Evolution Canyons," I (Mount Carmel) and
      II (Upper Galilee) in Israel. The family consists of five distinct subfamilies
      (kaiI-kaiV) comprising at least 20 functional genes and pseudogenes. The obtained
      data suggest that the duplications of kai genes have adaptive significance, and
      some of them are evolutionarily quite recent (approximately 80,000 years ago).
      The observed patterns of within- and between-subfamily polymorphisms indicate
      that positive diversifying, balancing, and purifying selections are the principal
      driving forces of the kai gene family's evolution.

PMID- 11842227
TI  - Disruption of primary auditory cortex by synchronous auditory inputs during a
      critical period.
AB  - In the primary auditory cortex (AI), the development of tone frequency
      selectivity and tonotopic organization is influenced by patterns of neural
      activity. Introduction of synchronous inputs into the auditory pathway achieved
      by exposing rat pups to pulsed white noise at a moderate intensity during P9-P28
      resulted in a disrupted tonotopicity and degraded frequency-response selectivity
      for neurons in the adult AI. The latter was manifested by broader-than-normal
      tuning curves, multipeaks, and discontinuous, tone-evoked responses within AI
      receptive fields. These effects correlated with the severe impairment of normal,
      developmental sharpening, and refinement of receptive fields and tonotopicity. In
      addition, paradoxically weaker than normal temporal correlations between the
      discharges of nearby AI neurons were recorded in exposed rats. In contrast, noise
      exposure of rats older than P30 did not cause significant change of auditory
      cortical maps. Thus, patterned auditory inputs appear to play a crucial role in
      shaping neuronal processing/decoding circuits in the primary auditory cortex
      during a critical period.

PMID- 11842228
TI  - Inhibitors of soluble epoxide hydrolase attenuate vascular smooth muscle cell
      proliferation.
AB  - Atherosclerosis, in its myriad incarnations the foremost killer disease in the
      industrialized world, is characterized by aberrant proliferation of vascular
      smooth muscle (VSM) cells in part as a result of the recruitment of inflammatory
      cells to the blood vessel wall. The epoxyeicosatrienoic acids are synthesized
      from arachidonic acid in a reaction catalyzed by the cytochrome P450 system and
      are vasoactive substances. Metabolism of these compounds by epoxide hydrolases
      results in the formation of compounds that affect the vasculature in a
      pleiotropic manner. As an outgrowth of our observations that urea inhibitors of
      the soluble epoxide hydrolase (sEH) reduce blood pressure in spontaneously
      hypertensive rats as well as the findings of other investigators that these
      compounds possess antiinflammatory actions, we have examined the effect of sEH
      inhibitors on VSM cell proliferation. We now show that the sEH inhibitor 1
      cyclohexyl-3-dodecyl urea (CDU) inhibits human VSM cell proliferation in a dose
      dependent manner and is associated with a decrease in the level of cyclin D1. In
      addition, cis-epoxyeicosatrienoic acid mimics the growth-suppressive activity of
      CDU; there is no evidence of cellular toxicity or apoptosis in CDU-treated cells
      when incubated with 20 microM CDU for up to 48 h. These results, in light of the
      antiinflammatory and antihypertensive properties of these compounds that have
      been demonstrated already, suggest that the urea class of sEH inhibitors may be
      useful for therapy for diseases such as hypertension and atherosclerosis
      characterized by exuberant VSM cell proliferation and vascular inflammation.

PMID- 11842231
TI  - Protein design from in silico dynamic information: the emergence of the 'turn
      dock-lock' motif.
AB  - A protein design methodology based on ab initio folding simulations is described
      and illustrated. First, the time evolution of the chain topology is generated to
      identify a collapse-triggering nucleus. Then, a minimal spliced sequence of
      nuclear residues is created and systematically mutated in silico until it can
      sustain a stable conformation retaining the original nucleus topology. The
      mutations introduce a structural compensation for the deletions and eventually
      lead to the recovery of the native fold motif beyond topological identity. For
      ubiquitin, the systematically modified sequence is predicted to be a resilient
      folder, since it is 92% homologous to the hyperthermophile variant of B1-domain
      in streptococcal protein G. The methodology enabling us to identify the nucleus
      is independently validated vis-a-vis site-directed mutagenesis experiments on
      chymotrypsin inhibitor (CI2).

PMID- 11842230
TI  - Mutation, specialization, and hypersensitivity in highly optimized tolerance.
AB  - We introduce a model of evolution in which competing organisms are represented by
      percolation lattice models. Fitness is based on the number of occupied sites
      remaining after removing a cluster connected to a randomly selected site. High
      fitness individuals arising through mutation and selection must trade off density
      versus robustness to loss, and are characterized by cellular barrier patterns
      that prevent large cascading losses to common disturbances. This model shows that
      Highly Optimized Tolerance (HOT), which links complexity to robustness in
      designed systems, arises naturally through Darwinian mechanisms. Although the
      model is a severe abstraction of biology, it produces a surprisingly wide variety
      of micro- and macroevolutionary features strikingly similar to real biological
      evolution.

PMID- 11842233
TI  - Determining the roles of different chain fragments in recognition of
      immunoglobulin fold.
AB  - We examine sequence-to-structure specificity of beta-structural fragments of
      immunoglobulin domains. The structure specificity of separate chain fragments is
      estimated by computing the Z-score values in recognition of the native structure
      in gapless threading tests. To improve the accuracy of our calculations we use
      energy averaging over diverse homologs of immunoglobulin domains. We show that
      the interactions between residues of beta-structure are more determinant in
      recognition of the native structure than the interactions within the whole chain
      molecule. This result distinguishes immunoglobulins from more typical proteins
      where the interactions between residues of the whole chain normally recognize the
      native fold more accurately than interactions between the residues of the
      secondary structure residues alone [Reva,B. and Topiol,S. (2000) BIOCOMPUTING:
      Proceedings of the Pacific Symposium. World Scientific Publishing Co., pp. 168
      178]. We also find that the predominant contributions of the secondary structure
      are produced by the four central beta-strands that form the core of the molecule.
      The results of this study allow us through quantitative means to understand the
      architecture of immunoglobulin molecules. Comparing the fold recognition data for
      different chain fragments one can say that beta-strands form a rigid frame for
      immunoglobulin molecules, whereas loops, with no structural role, can develop a
      broad variety of binding specificities. It is well known that protein function is
      determined by specific portions of a protein chain. This study suggests that the
      whole protein structure can be predominantly determined by a few fragments of
      chain which form the structural framework of the molecule. This idea may help in
      better understanding the mechanisms of protein evolution: strengthening a protein
      structure in the key framework-forming regions allows mutations and flexibility
      in other chain regions.

PMID- 11842232
TI  - Deriving structural and functional insights from a ligand-based hierarchical
      classification of G protein-coupled receptors.
AB  - G protein-coupled receptors (GPCRs) constitute the largest known family of cell
      surface receptors. With hundreds of members populating the rhodopsin-like GPCR
      superfamily and many more awaiting discovery in the human genome, they are of
      interest to the pharmaceutical industry because of the opportunities they afford
      for yielding potentially lucrative drug targets. Typical sequence analysis
      strategies for identifying novel GPCRs tend to involve similarity searches using
      standard primary database search tools. This will reveal the most similar
      sequence, generally without offering any insight into its family or superfamily
      relationships. Conversely, searches of most 'pattern' or family databases are
      likely to identify the superfamily, but not the closest matching subtype. Here we
      describe a diagnostic resource that allows identification of GPCRs in a
      hierarchical fashion, based principally upon their ligand preference. This
      resource forms part of the PRINTS database, which now houses approximately 250
      GPCR-specific fingerprints (http://www.bioinf.man.ac.uk/dbbrowser/gpcrPRINTS/).
      This collection of fingerprints is able to provide more sensitive diagnostic
      opportunities than have been realized by related approaches and is currently the
      only diagnostic tool for assigning GPCR subtypes. Mapping such fingerprints on to
      three-dimensional GPCR models offers powerful insights into the structural and
      functional determinants of subtype specificity.

PMID- 11842234
TI  - Probing the catalytically essential residues of the alpha-L-arabinofuranosidase
      from Thermobacillus xylanilyticus.
AB  - The alpha-L-arabinofuranosidase D3 from Thermobacillus xylanilyticus is an
      arabinoxylan-debranching enzyme which belongs to family 51 of the glycosyl
      hydrolase classification. Previous studies have indicated that members of this
      family are retaining enzymes and may form part of the 4/7 superfamily of glycosyl
      hydrolases. To investigate the active site of alpha-L-arabinofuranosidase D3, we
      have used sequence alignment, site-directed mutagenesis and kinetic analyses.
      Likewise, we have shown that Glu(28), Glu(176) and Glu(298) are important for
      catalytic activity. Kinetic data obtained for the mutant Glu(176)-->Gln, combined
      with the results of chemical rescue using the mutant Glu(176)-->Ala, have shown
      that Glu(176) is the acid-base residue. Moreover, NMR analysis of the arabinosyl
      azide adduct, which was produced by chemical rescue of the mutant Glu(176)-->Ala,
      indicated that alpha-L-arabinofuranosidase D3 hydrolyses glycosidic bonds with
      retention of the anomeric configuration. The results of similar chemical rescue
      studies using other mutant enzymes suggest that Glu(298) might be the catalytic
      nucleophile and that Glu(28) is a third member of a catalytic triad which may be
      responsible for modulating the ionization state of the acid-base and implicated
      in substrate fixation. Overall, these findings support the hypothesis that alpha
      L-arabinofuranosidase D3 belongs to the 4/7 superfamily and provide the first
      experimental evidence concerning the catalytic apparatus of a family 51
      arabinofuranosidase.

PMID- 11842229
TI  - Ischemic preconditioning acts upstream of GluR2 down-regulation to afford
      neuroprotection in the hippocampal CA1.
AB  - Animals subjected to sublethal transient global ischemia (ischemic
      preconditioning) exhibit neuroprotection against subsequent global ischemia
      induced neuronal death in the hippocampal CA1 (ischemic tolerance). The molecular
      mechanisms underlying ischemic tolerance are unclear. Here we report that
      ischemic preconditioning induced a small, transient down-regulation of GluR2 mRNA
      expression and greatly attenuated subsequent ischemia-induced GluR2 mRNA and
      protein down-regulation and neuronal death. Ischemic preconditioning and GluR2
      antisense knockdown acted synergistically to increase cell death. Sublethal
      antisense knockdown did not protect against subsequent ischemic insults or
      antisense knockdown. These findings indicate that ischemic preconditioning acts
      at step(s) upstream from suppression of GluR2 gene expression to afford
      neuroprotection and implicate transcriptional regulation of GluR2 expression in
      the adaptive mechanisms associated with ischemic tolerance.

PMID- 11842235
TI  - The effect of proline insertions on the thermostability of a barley alpha
      glucosidase.
AB  - The thermal stability of alpha-glucosidase is important because the conversion of
      starch to fermentable sugars during industrial production of ethanol (e.g.
      brewing, fuel ethanol production) typically takes place at temperatures of 65-73
      degrees C. In this study we investigate the thermostability of alpha-glucosidases
      from four plant species, compare their deduced amino acid sequences, and test the
      effect of substituting a proline for the residue present in the wild-type enzyme
      on the thermostability of alpha-glucosidase. The alpha-glucosidase from barley
      (Hordeum vulgare) was significantly less thermostable than the other three alpha
      glucosidases. A comparison of the published deduced amino acid sequences of these
      four alpha-glucosidases revealed conserved proline residues in the three most
      thermostable alpha-glucosidases that were not found in the barley enzyme. Site
      directed mutagenesis was done on recombinant barley alpha-glucosidase to create
      proteins with prolines at these conserved positions. The thermostability (T(50))
      of one of these mutant enzymes, T340P, was 10 degrees C higher than the non
      mutated enzyme.

PMID- 11842236
TI  - An absolute requirement of fructose 1,6-bisphosphate for the Lactobacillus casei
      L-lactate dehydrogenase activity induced by a single amino acid substitution.
AB  - Lactobacillus casei allosteric L-lactate dehydrogenase (L-LDH) absolutely
      requires fructose 1,6-bisphosphate [Fru(1,6)P2] for its catalytic activity under
      neutral conditions, but exhibits marked catalytic activity in the absence of
      Fru(1,6)P(2) under acidic conditions through the homotropic activation effect of
      substrate pyruvate. In this enzyme, a single amino acid replacement, i.e. that of
      His205 conserved in the Fru(1,6)P(2)-binding site of certain allosteric L-LDHs of
      lactic acid bacteria with Thr, did not induce a marked loss of the activation
      effect of Fru(1,6)P(2) or divalent metal ions, which are potent activators that
      improve the activation function of Fru(1,6)P(2) under neutral conditions.
      However, this replacement induced a great loss of the Fru(1,6)P(2)-independent
      activation effect of pyruvate or pyruvate analogs under acidic conditions,
      consequently indicating an absolute Fru(1,6)P(2) requirement for the enzyme
      activity. The replacement also induced a significant reduction in the pH
      dependent sensitivity of the enzyme to Fru(1,6)P(2), through a slight decrease
      and increase of the Fru(1,6)P(2) sensitivity under acidic and neutral conditions,
      respectively, indicating that His205 is also largely involved in the pH-dependent
      sensitivity of L.casei L-LDH to Fru(1,6)P(2). The role of His205 in the
      allosteric regulation of the enzyme is discussed on the basis of the known
      crystal structures of L-LDHs.

PMID- 11842237
TI  - Acetylcholinesterase engineering for detection of insecticide residues.
AB  - To detect traces of insecticides in the environment using biosensors, we
      engineered Drosophila acetylcholinesterase (AChE) to increase its sensitivity and
      its rate of phosphorylation or carbamoylation by organophosphates or carbamates.
      The mutants made by site-directed mutagenesis were expressed in baculovirus.
      Different strategies were used to obtain these mutants: (i) substitution of amino
      acids at positions found mutated in AChE from insects resistant to insecticide,
      (ii) mutations of amino acids at positions suggested by 3-D structural analysis
      of the active site, (iii) Ala-scan analysis of amino acids lining the active site
      gorge, (iv) mutagenesis at positions detected as important for sensitivity in the
      Ala-scan analysis and (v) combination of mutations which independently enhance
      sensitivity. The results highlighted the difficulty of predicting the effect of
      mutations; this may be due to the structure of the site, a deep gorge with the
      active serine at the bottom and to allosteric effects between the top and the
      bottom of the gorge. Nevertheless, the use of these different strategies allowed
      us to obtain sensitive enzymes. The greatest improvement was for the sensitivity
      to dichlorvos for which a mutant was 300-fold more sensitive than the Drosophila
      wild-type enzyme and 288 000-fold more sensitive than the electric eel enzyme,
      the enzyme commonly used to detect organophosphate and carbamate.

PMID- 11842238
TI  - A minimal receptor-Ig chimera of human FcepsilonRI alpha-chain efficiently binds
      secretory and membrane IgE.
AB  - We constructed a soluble minimal receptor-Ig chimera in which the two
      extracellular domains of human Fcepsilonhain (D1 and D2) were fused to the
      dimerizing C-terminal domain of human IgG1 heavy chain (gamma1-CH3). The protein
      was expressed and actively secreted by Chinese hamster ovary (CHO) cells as a
      fully glycosylated soluble dimeric protein. It showed efficient binding both to
      human membrane-bound IgE isoforms and to the two secretory IgE isoforms.
      Moreover, the dimeric receptor binds IgE with the expected 1:2 stoichiometry. The
      receptor-Ig chimera, in 2-fold molar excess, inhibited engagement of secretory
      IgE to rat basophilic leukemia cells expressing the human alphabetagamma
      receptor. Full self-nature and inability to bind Fcgamma receptors make this
      protein an attractive candidate for clinical applications and a novel
      biotechnological tool for atopic allergy research.

PMID- 11842239
TI  - Effect of the intermolecular disulfide bond on the conformation and stability of
      glial cell line-derived neurotrophic factor.
AB  - Glial cell line-derived neurotrophic factor (GDNF) is a member of the TGF-beta
      superfamily of proteins. It exists as a covalent dimer in solution, with the 15
      kDa monomers linked by an interchain disulfide bond through the Cys101 residues.
      Sedimentation equilibrium and velocity experiments demonstrated that, after
      removal of the interchain disulfide bond, GDNF remains as a non-covalent dimer
      and is stable at pH 7.0. To investigate the effect of the intermolecular
      disulfide on the structure and stability of GDNF, we compared the solution
      structures of the wild-type protein and a cysteine-101 to alanine (C101A) mutant
      using Fourier transform infrared (FTIR), FT-Raman and circular dichroism (CD)
      spectroscopy and sedimentation analysis. The elimination of the intermolecular
      disulfide bond causes only minor changes (approximately 4%) in the secondary
      structures of GDNF. The far- and near-UV CD spectra demonstrated that the
      secondary and tertiary structures were similar for both wild-type and C101A GDNF.
      Heparin binding and sedimentation velocity experiments also indicated that the
      folded structure of the wild-type and C101A GDNF are indistinguishable. The
      thermal stability of GDNF does not appear to be affected by the absence of the
      interchain disulfide bond and the biological activity of the C101A mutant is
      identical with that of the wild-type protein. However, small but significant
      changes in side chain conformations of tyrosine and aliphatic residues were
      observed by FT-Raman spectroscopy upon removal of the intermolecular disulfide
      bond, which may reflect structural changes in the area of dimeric contact. By
      comparing the Raman spectrum of wild-type GDNF with that of the C101A analog, we
      identified the conformation of the intermolecular disulfide as trans-gauche-trans
      geometry. These results indicate that GDNF is an active, properly folded molecule
      in the absence of the interchain disulfide bond.

PMID- 11842240
TI  - Mechanotransduction: all signals point to cytoskeleton, matrix, and integrins.
AB  - Mechanical stresses modulate cell function by either activating or tuning signal
      transduction pathways. Mechanotransduction, the process by which cells convert
      mechanical stimuli into a chemical response, occurs both in cells specialized for
      sensing mechanical cues and in parenchymal cells whose primary function is not
      mechanosensory. However, common among the various responses to mechanical stress
      is the importance of direct or indirect connections between the internal
      cytoskeleton, the extracellular matrix (ECM), and traditional signal transducing
      molecules. In many instances, these elements converge at focal adhesions, sites
      of structural attachment between the cytoskeleton and ECM that are anchored by
      cell surface integrin receptors. Alenghat and Ingber discuss the accumulating
      evidence for the central role of cytoskeleton, ECM, and integrin-anchored focal
      adhesions in several mechanotransduction pathways.

PMID- 11842241
TI  - ECM remodeling regulates angiogenesis: endothelial integrins look for new
      ligands.
AB  - The process of angiogenesis is a dynamic one. Vascular endothelial cells are
      changing at the same time the extracellular matrix is being remodeled. Stupack
      and Cheresh discuss how remodeling of the extracellular matrix (ECM) and changes
      in the endothelial cell protein production and integrin expression contribute to
      the complex process of new blood vessel growth from an existing vascular bed.

PMID- 11842242
TI  - Knowing how to navigate: mechanisms of semaphorin signaling in the nervous
      system.
AB  - Neuronal connections are made during embryonic development with astonishing
      precision to ultimately form the physical basis for the central nervous system's
      main capacity: information processing. Over the past few decades, much has been
      learned about the general principles of axon guidance. A key finding to emerge is
      that extracellular cues play decisive roles in establishing the connections. One
      family of such cues, the semaphorin proteins, was first identified as repellents
      for navigating axons during brain wiring. Recent studies have implicated these
      molecules in many other processes of neuronal development, including axonal
      fasciculation, target selection, neuronal migration, and dendritic guidance, as
      well as in the remodeling and repair of the adult nervous system. It appears that
      responding neuronal processes sense these semaphorin signals by a family of
      transmembrane molecules, namely the plexins, even though neuropilins were also
      found to be required for mediating the interaction between plexins and class 3
      semaphorins. Our understanding of the intracellular signaling machinery linking
      the receptors to the cytoskeleton machinery is still incomplete, but several
      molecules have been implicated in mediating or modulating semaphorin-induced
      responses. Adding to the complexity of semaphorin biology, new findings implicate
      semaphorins in functioning not only as signaling ligands, but also as signal
      transducing receptors. Thus, semaphorins may serve as important probes for
      exploring the mechanisms of intercellular communication during the development
      and function of the nervous system.

PMID- 11842243
TI  - Cytolytic viruses as potential anti-cancer agents.
AB  - The resistance of cancers to conventional therapies has inspired the search for
      novel strategies. One such approach, namely gene therapy, is based upon the
      introduction of genes such as those encoding suicide proteins, tumour suppressor
      proteins or cytokines into tumour cells by means of a genetic vector. The
      efficiency with which viruses transfer their genes from one host cell to another
      has led to the widespread use of viruses as genetic vectors. For safety reasons,
      such virus vectors are generally replication-defective but, unfortunately, this
      has limited the efficacy of treatment by restricting the number of cells to which
      the therapeutic gene is delivered. For this reason, the use of replication
      competent viruses has been proposed, since virus replication would be expected to
      lead to amplification and spread of the therapeutic genes in vivo. The
      replication of many viruses results in lysis of the host cells. This inherent
      cytotoxicity, together with the efficiency with which viruses can spread from one
      cell to another, has inspired the notion that replication-competent viruses could
      be exploited for cancer treatment. Some viruses have been shown to replicate more
      efficiently in transformed cells but it is unlikely that such examples will
      exhibit a high enough degree of tumour selectivity, and hence safety, for the
      treatment of patients. Our increasing knowledge of the pathogenesis of virus
      disease and the ability to manipulate specific regions of viral genomes have
      allowed the construction of viruses that are attenuated in normal cells but
      retain their ability to lyse tumour cells. Such manipulations have included
      modifying the ability of viruses to bind to, or replicate in, particular cell
      types, while others have involved the construction of replication-competent
      viruses encoding suicide proteins or cytokines. Naturally occurring or
      genetically engineered oncolytic viruses based upon adenovirus, herpes simplex
      virus, Newcastle disease virus, poliovirus, vesicular stomatitis virus, weasles
      virus and reovirus have been described. The results of animal studies are
      encouraging and a number of viruses are now being evaluated in clinical trials.

PMID- 11842244
TI  - The hinge region of the human papillomavirus type 8 E2 protein activates the
      human p21(WAF1/CIP1) promoter via interaction with Sp1.
AB  - The E2 proteins regulate papillomavirus (PV) gene expression by sequence-specific
      DNA binding. However, E2 is also able to activate in the absence of E2 binding
      sites. We show here that the E2 protein of human PV type 8 (HPV8) can activate
      the expression of p21(WAF1/CIP1) via promoter-proximal 200 nucleotides, which
      contain several Sp1 binding sites and no E2 binding sites. HPV8 E2 lacking the
      activation domain, which is rather conserved among E2 proteins, cooperated with
      co-expressed Sp1 in stimulation of the p21(WAF1/CIP1) promoter, in contrast to
      HPV18 E2 lacking the activation domain. We can demonstrate that the internal non
      conserved hinge region of HPV8 E2 is sufficient for this functional cooperativity
      with Sp1. In correlation, the hinge of HPV8 E2 directly binds to Sp1. These
      results suggest that HPV8 E2 might be able to 'super'-activate Sp1-mediated
      transcription by a direct interaction via the non-conserved hinge region.

PMID- 11842245
TI  - Topors, a p53 and topoisomerase I binding protein, interacts with the adeno
      associated virus (AAV-2) Rep78/68 proteins and enhances AAV-2 gene expression.
AB  - The adeno-associated virus type 2 (AAV-2) Rep proteins are essential for AAV DNA
      replication and regulation of AAV gene expression. We have identified a cellular
      protein interacting with Rep78 and Rep68 in yeast two-hybrid analysis and in GST
      pull-down assays. This protein has recently been described as both a p53 (p53BP3)
      and a topoisomerase I interacting protein (Topors). It contains an
      arginine/serine-rich domain, a RING finger domain and five PEST sequences. A
      minimal sequence sufficient for interaction with Rep was mapped to Topors amino
      acids 871 to 917. We show that the same region is also involved in the
      interaction with p53. Rep sequences involved in interaction with Topors were
      mapped to Rep amino acids 172 to 481. Overexpression of Topors stimulated AAV
      gene expression in the absence of helper virus, suggesting a function of Topors
      as a transcriptional regulator.

PMID- 11842246
TI  - Analysis of DNA binding by the adenovirus type 5 E1A oncoprotein.
AB  - Adenovirus type 5 E1A proteins interact with cellular regulators of transcription
      to reprogram gene expression in the infected or transformed cell. Although E1A
      also interacts with DNA directly in vitro, it is not clear how this relates to
      its function in vivo. The N-terminal conserved regions 1, 2 and 3 and the C
      terminal portions of E1A were prepared as purified recombinant proteins and
      analyses showed that only the C-terminal region bound DNA in vitro. Deletion of
      E1A amino acids 201-220 inhibited binding and a minimal fragment encompassing
      amino acids 201-218 of E1A was sufficient for binding single- and double-stranded
      DNA. This portion of E1A also bound the cation-exchange resins cellulose
      phosphate and carboxymethyl Sepharose. As this region contains six basic amino
      acids, in vitro binding of E1A to DNA probably results from an ionic interaction
      with the phosphodiester backbone of DNA. Studies in Saccharomyces cerevisiae have
      shown that expression of a strong transcriptional activation domain fused to a
      DNA-binding domain can inhibit growth. Although fusion of the C-terminal region
      of E1A to a strong transcriptional activation domain inhibited growth when
      expressed in yeast, this was not mediated by the DNA-binding domain identified in
      vitro. These data suggest that E1A does not bind DNA in vivo.

PMID- 11842247
TI  - Polymorphism of open reading frame 71 of equine herpesvirus-4 (EHV-4) and EHV-1.
AB  - Open reading frame (ORF) 71 genes of both equine herpesvirus-1 (EHV-1) and EHV-4
      encode a unique glycoprotein, which has been described to vary in molecular mass
      from 200 to 450 kDa. Using PCR and nucleotide sequence analysis, it was shown
      that the ORF 71 genes of EHV-1 and EHV-4 are polymorphic due to a variable number
      of reiterated sequences in two regions, designated regions A and B. Region A was
      threonine-rich and was located near the N terminus. Region B comprised a 38 amino
      acid repeat near the C terminus that expanded following cell culture adaptation.
      Western blot analysis of viruses showed that EHV-4 gp2 was modified by
      glycosylation and that variation in region A resulted in the marked differences
      in the molecular mass of EHV-4 gp2.

PMID- 11842248
TI  - Isolation and expression of three open reading frames from ovine herpesvirus-2.
AB  - Ovine herpesvirus-2 (OvHV-2), a member of the gammaherpesviruses (genus
      Rhadinovirus), asymptomatically infects its natural host, the sheep, but causes
      malignant catarrhal fever (MCF) in susceptible hosts, such as cattle, deer and
      pigs. A permissive cell culture system for virus replication has not been
      identified but viral DNA is present within lymphoblastoid cell lines (LCLs)
      established from cases of MCF. During this study, a cDNA expression library
      generated from LCLs was screened with sheep sera and two cDNAs were isolated. One
      cDNA contained two open reading frames (ORFs) that show similarity to ORFs 58 and
      59 of alcelaphine herpesvirus-1 (AlHV-1), a closely related gammaherpesvirus that
      also causes MCF. Both ORFs 58 and 59 are conserved throughout the
      gammaherpesviruses. ORF 58 is predicted to be a membrane protein, while ORF 59
      has been shown to be an early lytic gene that functions as a DNA polymerase
      processivity factor. The second cDNA clone contained a partial ORF showing
      limited similarity to AlHV-1 ORF 73, a homologue of the latency-associated
      nuclear antigen of human herpesvirus-8, which is associated with latent
      infections. The full-length OvHV-2 ORF 73 was cloned subsequently by PCR. The
      ORFs isolated from the library were cloned into a bacterial expression vector and
      the recombinant proteins tested for their reactivity to sera from OvHV-2-infected
      animals. An ORF 59 fusion protein was recognized specifically by sera from OvHV-2
      infected cattle and will be used to develop a sero-diagnostic test.

PMID- 11842249
TI  - The vaccinia virus soluble interferon-gamma receptor is a homodimer.
AB  - The vaccinia virus (VV) interferon (IFN)-gamma receptor (IFN-gammaR) is a 43 kDa
      soluble glycoprotein that is secreted from infected cells early during infection.
      Here we demonstrate that the IFN-gammaR from VV, cowpox virus and camelpox virus
      exists naturally as a homodimer, whereas the cellular IFN-gammaR dimerizes only
      upon binding the homodimeric IFN-gamma. The existence of the virus protein as a
      dimer in the absence of ligand may provide an advantage to the virus in efficient
      binding and inhibition of IFN-gamma in solution.

PMID- 11842250
TI  - Identification of T-cell epitopes in the structural and non-structural proteins
      of classical swine fever virus.
AB  - To identify new T-cell epitopes of classical swine fever virus (CSFV), 573
      overlapping, synthetic pentadecapeptides spanning 82% of the CSFV (strain
      Glentorf) genome sequence were synthesized and screened. In proliferation assays,
      26 peptides distributed throughout the CSFV viral protein sequences were able to
      induce specific T-cell responses in PBMCs from a CSFV-Glentorf-infected d/d
      haplotype pig. Of these 26 peptides, 18 were also recognized by PBMCs from a CSFV
      Alfort/187-infected d/d haplotype pig. In further experiments, it could be shown
      that peptide 290 (KHKVRNEVMVHWFDD), which corresponds to amino acid residues 1446
      1460 of the CSFV non-structural protein NS2-3 could induce interferon-gamma
      secretion after secondary in vitro restimulation. The major histocompatibility
      complex (MHC) restriction for stimulation of T-cells by this pentadecapeptide was
      identified as being mainly MHC class II and partially MHC class I. In cytolytic
      assays, CSFV-specific cytotoxic T-lymphocytes (CTLs) were able to lyse peptide
      290-loaded target cells. These findings indicate the existence of a CSFV-specific
      helper T-cell epitope and a CTL epitope in this peptide.

PMID- 11842251
TI  - Expression of hepatitis C virus envelope glycoproteins by herpes simplex virus
      type 1-based amplicon vectors.
AB  - Herpes simplex virus type 1 (HSV-1)-based amplicon vectors expressing hepatitis C
      virus (HCV) E1 and E2 glycoproteins were investigated. HSV-1 amplicon vectors
      carrying the E1E2p7- or E2p7-coding sequences of HCV type 1a under the control of
      the HSV-1 IE4 (alpha22/alpha47) promoter were constructed. Studies of infected
      HepG2, WRL 68 or Vero cells indicated that HSV-1-based amplicon vectors express
      high levels of HCV glycoproteins that are processed correctly. Immunofluorescence
      microscopy combined with immunoprecipitation and endoglycosidase treatment of
      cells infected with the HSV-1-based vectors expressing E1 and E2 showed that the
      two glycoproteins were retained in the endoplasmic reticulum and had the expected
      glycosylation patterns. Furthermore, although most of the E1 and E2 proteins
      formed disulfide-linked aggregates, significant amounts of monomeric forms of the
      two proteins were detected by SDS-PAGE under non-reducing conditions, suggesting
      the presence of non-covalently associated E1 and E2. Similar results were
      produced by a replication-competent recombinant HSV-1 vector expressing HCV E1
      and E2. These results indicated that HSV-1-based amplicon vectors represent a
      useful expression system for the study of HCV glycoproteins.

PMID- 11842252
TI  - In vitro and in vivo expression of foreign genes by transmissible gastroenteritis
      coronavirus-derived minigenomes.
AB  - A helper-dependent expression system based on transmissible gastroenteritis
      coronavirus (TGEV) has been developed using a minigenome of 3.9 kb (M39).
      Expression of the reporter gene beta-glucuronidase (GUS) (2-8 microg per 10(6)
      cells) and the porcine respiratory and reproductive syndrome virus (PRRSV) ORF5
      (1-2 microg per 10(6) cells) has been shown using a TGEV-derived minigenome. GUS
      expression levels increased about eightfold with the m.o.i. and were maintained
      for more than eight passages in cell culture. Nevertheless, instability of the
      GUS and ORF5 subgenomic mRNAs was observed from passages five and four,
      respectively. About a quarter of the cells in culture expressing the helper virus
      also produced the reporter gene as determined by studying GUS mRNA production by
      in situ hybridization or immunodetection to visualize the protein synthesized.
      Expression of GUS was detected in the lungs, but not in the gut, of swine
      immunized with the virus vector. Around a quarter of lung cells showing
      replication of the helper virus were also positive for the reporter gene.
      Interestingly, strong humoral immune responses to both GUS and PRRSV ORF5 were
      induced in swine with this virus vector. The large cloning capacity and the
      tissue specificity of the TGEV-derived minigenomes suggest that these virus
      vectors are very promising for vaccine development.

PMID- 11842253
TI  - Mutational analysis of the active centre of coronavirus 3C-like proteases.
AB  - Formation of the coronavirus replication-transcription complex involves the
      synthesis of large polyprotein precursors that are extensively processed by virus
      encoded cysteine proteases. In this study, the coding sequence of the feline
      infectious peritonitis virus (FIPV) main protease, 3CL(pro), was determined.
      Comparative sequence analyses revealed that FIPV 3CL(pro) and other coronavirus
      main proteases are related most closely to the 3C-like proteases of potyviruses.
      The predicted active centre of the coronavirus enzymes has accepted unique
      replacements that were probed by extensive mutational analysis. The wild-type
      FIPV 3CL(pro) domain and 25 mutants were expressed in Escherichia coli and tested
      for proteolytic activity in a peptide-based assay. The data strongly suggest
      that, first, the FIPV 3CL(pro) catalytic system employs His(41) and Cys(144) as
      the principal catalytic residues. Second, the amino acids Tyr(160) and His(162),
      which are part of the conserved sequence signature Tyr(160)-Met(161)-His(162) and
      are believed to be involved in substrate recognition, were found to be
      indispensable for proteolytic activity. Third, replacements of Gly(83) and
      Asn(64), which were candidates to occupy the position spatially equivalent to
      that of the catalytic Asp residue of chymotrypsin-like proteases, resulted in
      proteolytically active proteins. Surprisingly, some of the Asn(64) mutants even
      exhibited strongly increased activities. Similar results were obtained for human
      coronavirus (HCoV) 3CL(pro) mutants in which the equivalent Asn residue (HCoV
      3CL(pro) Asn(64)) was substituted. These data lead us to conclude that both the
      catalytic systems and substrate-binding pockets of coronavirus main proteases
      differ from those of other RNA virus 3C and 3C-like proteases.

PMID- 11842254
TI  - Conservation of substrate specificities among coronavirus main proteases.
AB  - The key enzyme in coronavirus replicase polyprotein processing is the coronavirus
      main protease, 3CL(pro). The substrate specificities of five coronavirus main
      proteases, including the prototypic enzymes from the coronavirus groups I, II and
      III, were characterized. Recombinant main proteases of human coronavirus (HCoV),
      transmissible gastroenteritis virus (TGEV), feline infectious peritonitis virus,
      avian infectious bronchitis virus and mouse hepatitis virus (MHV) were tested in
      peptide-based trans-cleavage assays. The determination of relative rate constants
      for a set of corresponding HCoV, TGEV and MHV 3CL(pro) cleavage sites revealed a
      conserved ranking of these sites. Furthermore, a synthetic peptide representing
      the N-terminal HCoV 3CL(pro) cleavage site was shown to be effectively hydrolysed
      by noncognate main proteases. The data show that the differential cleavage
      kinetics of sites within pp1a/pp1ab are a conserved feature of coronavirus main
      proteases and lead us to predict similar processing kinetics for the replicase
      polyproteins of all coronaviruses.

PMID- 11842255
TI  - N-Glycans attached to the stem domain of haemagglutinin efficiently regulate
      influenza A virus replication.
AB  - The haemagglutinin (HA) protein of fowl plague virus A/FPV/Rostock/34 (H7N1)
      contains three N-linked oligosaccharide side chains in its stem domain. These
      stem glycans, which are attached to the Asn residues at positions 12, 28 and 478,
      are highly conserved throughout all HA protein sequences analysed to date. In a
      previous study, in which mutant HA proteins lacking individual stem glycosylation
      sites had been expressed from an SV-40 vector, it was shown that these glycans
      maintain the HA protein in the metastable form required for fusion activity. In
      the present study, the functional role of the stem N-glycans for virus
      replication was investigated using recombinant influenza viruses generated by an
      RNA polymerase I-based system. Studies in Madin-Darby canine kidney cells and
      embryonated chickens' eggs revealed that the N-glycan at Asn(12) is crucial for
      virus replication. In both culture systems, growth of virus lacking this glycan
      (mutant cg1) was completely blocked at 37 degrees C and inhibited at 33 degrees
      C. Loss of the glycan from Asn(478) (mutant cg3) caused less striking, but still
      measurable, effects. Interestingly, it was not possible to generate mutant
      viruses containing the HA protein lacking the N-glycan at Asn(28). It is
      concluded from this that the N-glycan at Asn(28) is indispensable for the
      formation of replication-competent influenza viruses. When compared to viruses
      containing wild-type HA protein, mutants cg1 and cg3 showed a significantly
      decreased pH stability. Taken together, these data show that the HA stem glycans
      are potent regulators of influenza virus replication.

PMID- 11842256
TI  - Caveolin-1 is incorporated into mature respiratory syncytial virus particles
      during virus assembly on the surface of virus-infected cells.
AB  - We have employed immunofluorescence microscopy and transmission electron
      microscopy to examine the assembly and maturation of respiratory syncytial virus
      (RSV) in the Vero cell line C1008. RSV matures at the apical cell surface in a
      filamentous form that extends from the plasma membrane. We observed that
      inclusion bodies containing viral ribonucleoprotein (RNP) cores predominantly
      appeared immediately below the plasma membrane, from where RSV filaments form
      during maturation at the cell surface. A comparison of mock-infected and RSV
      infected cells by confocal microscopy revealed a significant change in the
      pattern of caveolin-1 (cav-1) fluorescence staining. Analysis by immuno-electron
      microscopy showed that RSV filaments formed in close proximity to cav-1 clusters
      at the cell surface membrane. In addition, immuno-electron microscopy showed that
      cav-1 was closely associated with early budding RSV. Further analysis by confocal
      microscopy showed that cav-1 was subsequently incorporated into the envelope of
      RSV filaments maturing on the host cell membrane, but was not associated with
      other virus structures such as the viral RNPs. Although cav-1 was incorporated
      into the mature virus, it was localized in clusters rather than being uniformly
      distributed along the length of the viral filaments. Furthermore, when RSV
      particles in the tissue culture medium from infected cells were examined by
      immuno-negative staining, the presence of cav-1 on the viral envelope was clearly
      demonstrated. Collectively, these findings show that cav-1 is incorporated into
      the envelope of mature RSV particles during egress.

PMID- 11842257
TI  - Six-helix bundle assembly and characterization of heptad repeat regions from the
      F protein of Newcastle disease virus.
AB  - Paramyxoviruses may adopt a similar fusion mechanism to other enveloped viruses,
      in which an anti-parallel six-helix bundle structure is formed post-fusion in the
      heptad repeat (HR) regions of the envelope fusion protein. In order to understand
      the fusion mechanism and identify fusion inhibitors of Newcastle disease virus
      (NDV), a member of the Paramyxoviridae family, we have developed an E. coli
      system that separately expresses the F protein HR1 and HR2 regions as GST fusion
      proteins. The purified cleaved HR1 and HR2 have subsequently been assembled into
      a stable six-helix bundle heterotrimer complex. Furthermore, both the GST fusion
      protein and the cleaved HR2 show virus-cell fusion inhibition activity (IC(50) of
      1.07-2.93 microM). The solubility of the GST-HR2 fusion protein is much higher
      than that of the corresponding peptide. Hence this provides a plausible method
      for large-scale production of HR peptides as virus fusion inhibitors.

PMID- 11842258
TI  - Immunological changes in simian immunodeficiency virus (SIV(agm))-infected
      African green monkeys (AGM): expanded cytotoxic T lymphocyte, natural killer and
      B cell subsets in the natural host of SIV(agm).
AB  - The African green monkey (AGM) model system for simian immunodeficiency virus
      (SIV(agm)) has been used to examine why prolonged infection with the relevant
      virus does not result in the development of immunodeficiency in its natural host.
      Blood lymphocyte subset values were determined in uninfected (n=88) and naturally
      SIV(agm)-infected AGMs (n=74). A number of blood cell subsets, such as
      CD8alpha(+)CD3(+)CD28(neg), CD8alpha(+)CD3(neg) and CD20(+) cells, were expanded
      significantly in clinically asymptomatic animals carrying a relatively high
      plasma load of viral RNA (10(4)-10(7) RNA copies/ml plasma). The expanded
      CD8alpha(+)CD3(+)CD28(neg) subpopulation (1094 +/- 986 cells/microl blood in
      infected animals versus 402 +/- 364 cells/microl blood, P=0.03) comprised cells
      that resembled terminally differentiated effector CD8 T cells (CD27(neg) and
      CD11a(+)). In SIV(agm)-infected animals, the expanded CD8alpha(+)CD3(neg) cell
      subset shared identity with the CD16(+) population (natural killer cells). These
      results demonstrate for the first time that apathogenic SIV(agm) infection causes
      significant changes in the immune system of its natural host. Although previous
      studies had indicated that noncytotoxic mechanisms might play an important role
      in the suppression of virus replication in the natural host of SIV(agm), this
      study sheds new light on the possible role of cytotoxic T lymphocytes, the innate
      immune system and double-positive T helper cells (CD4(+)CD8alpha(+)CD3(+)) in
      suppressing virus replication in this animal model of AIDS.

PMID- 11842259
TI  - Presentation of a new H-2D(k)-restricted epitope in the Tax protein of human T
      lymphotropic virus type I is enhanced by the proteasome inhibitor lactacystin.
AB  - Tax, the trans-activator of human T-lymphotropic virus type I (HTLV-I), is the
      dominant target antigen for cytotoxic T lymphocytes (CTLs) in the majority of
      infected individuals, although the reason for this immunodominance is not clear.
      Tax has been shown to associate physically with the proteasome, a protease that
      is responsible for the generation of the majority of major histocompatibility
      complex (MHC) class I ligands recognized by CTLs. This association could lead to
      the preferential targeting of Tax to the MHC class I pathway and account for its
      high immunogenicity. Here, the CTL response to Tax was investigated in mice by
      priming with a Tax expression vector and boosting with a Tax recombinant vaccinia
      virus (modified vaccinia virus Ankara strain). This approach led to the
      identification of a new H-2D(k)-restricted epitope in Tax, amino acid residues 38
      46, sequence ARLHRHALL. Surprisingly, presentation of this epitope was found to
      be enhanced by the proteasome inhibitor lactacystin, although Tax was shown to
      associate with proteasomes in murine cells. The difficulties encountered in
      generating Tax-specific CTL responses and the results of enzyme-linked immunospot
      (ELISpot) analysis suggested that Tax is only poorly immunogenic for CTLs in
      mice. Therefore, the immunodominance of Tax in human CTL responses to HTLV-I is
      probably not due to an intrinsic property of the protein itself, such as an
      association with the proteasome, but instead may result from the fact that Tax is
      the predominant protein synthesized early after infection.

PMID- 11842260
TI  - Dual-colour imaging of membrane protein targeting directed by poa semilatent
      virus movement protein TGBp3 in plant and mammalian cells.
AB  - The movement function of poa semilatent hordeivirus (PSLV) is mediated by the
      triple gene block (TGB) proteins, of which two, TGBp2 and TGBp3, are membrane
      proteins. TGBp3 is localized to peripheral bodies in the vicinity of the plasma
      membrane and is able to re-direct TGBp2 from the endoplasmic reticulum (ER) to
      the peripheral bodies. For imaging of TGBp3-mediated protein targeting, PSLV
      TGBp3 tagged with a red fluorescent protein (DsRed) was used. Coexpression of
      DsRed-TGBp3 with GFP targeted to the ER lumen (ER-GFP) demonstrated that ER-GFP
      was contained in typical ER structures and peripheral bodies formed by TGBp3
      protein, suggesting an ER origin for these bodies. In transient coexpression with
      viral membrane proteins tagged with GFP, DsRed-TGBp3 directed to the peripheral
      bodies the homologous TGBp2 protein and two unrelated membrane proteins, the 6
      kDa movement protein of beet yellows closterovirus and the putative movement
      protein encoded by the genome component 4 of faba bean necrotic yellows
      nanovirus. However, coexpression of TGBp3 with GFP derivatives targeted to the ER
      membranes by artificial hydrophobic tail sequences suggested that targeting to
      the ER membranes per se was not sufficient for TGBp3-directed protein trafficking
      to peripheral bodies. TGBp3-induced targeting of TGBp2 also occurred in mammalian
      cells, indicating the universal nature of the protein trafficking signals and the
      cotargeting mechanism.

PMID- 11842261
TI  - Factors determining vector competence and specificity for transmission of Tomato
      spotted wilt virus.
AB  - The competence of a Frankliniella occidentalis and a Thrips tabaci population to
      transmit Tomato spotted wilt virus (TSWV) was analysed. Adults of the F.
      occidentalis population transmitted this virus efficiently, whereas those of the
      thelytokous T. tabaci population failed to transmit. TSWV replicated in the
      midgut of the larvae of both populations after ingestion of virus; however, lower
      amounts accumulated in T. tabaci larvae than in F. occidentalis larvae. The virus
      was almost undetectable in T. tabaci adults, whereas high titres were readily
      detected in the F. occidentalis adults. The first infections in F. occidentalis
      larvae were detected by immunocytochemical studies in midgut epithelial and
      subsequently in midgut muscle cells, the ligaments, and finally in the salivary
      glands. The infections were weaker in the midgut epithelial and muscle cells of
      T. tabaci larvae, followed by an almost complete absence of any infection in the
      ligaments, and a complete absence in the salivary glands. Studies by electron
      microscopy revealed the budding of some virus particles from the basal membrane
      of midgut epithelial cells of F. occidentalis larvae into the extracellular space
      of the basal labyrinth. Enveloped virus particles were also seen in midgut muscle
      cells of F. occidentalis larvae. They were not discerned in epithelial and muscle
      cells of T. tabaci larvae and adults. This study showed that the rate of virus
      replication in the midgut and the extent of virus migration from the midgut to
      the visceral muscle cells and the salivary glands are probably crucial factors in
      the determination of vector competence.

PMID- 11842262
TI  - Comparative analysis of the complete genome sequences of Helicoverpa zea and
      Helicoverpa armigera single-nucleocapsid nucleopolyhedroviruses.
AB  - The complete nucleotide sequence of Helicoverpa zea single-nucleocapsid
      nucleopolyhedrovirus (HzSNPV) has been determined (130869 bp) and compared to the
      nucleotide sequence of Helicoverpa armigera (Ha) SNPV. These two genomes are very
      similar in their nucleotide (97% identity) and amino acid (99% identity)
      sequences. The coding regions are much more conserved than the non-coding
      regions. In HzSNPV/HaSNPV, the 63 open reading frames (ORFs) present in all
      baculoviruses sequenced so far are much more conserved than other ORFs. HzSNPV
      has four additional small ORFs compared with HaSNPV, one of these (Hz42) being in
      a correct transcriptional context. The major differences between HzSNPV and
      HaSNPV are found in the sequence and organization of the homologous regions (hrs)
      and the baculovirus repeat ORFs (bro genes). The sequence identity between the
      HzSNPV and HaSNPV hrs ranges from 90% (hr1) to almost 100% (hr5) and the hrs
      differ in the presence/absence of one or more type A and/or B repeats. The three
      HzSNPV bro genes differ significantly from those in HaSNPV and may have been
      acquired independently in the ancestral past. The sequence data suggest strongly
      that HzSNPV and HaSNPV are variants of the same virus species, a conclusion that
      is supported by the physical and biological data.

PMID- 11842263
TI  - Partial redistribution of the Autographa californica nucleopolyhedrovirus
      chitinase in virus-infected cells accompanies mutation of the carboxy-terminal
      KDEL ER-retention motif.
AB  - During virus infection of insect cells, the Autographa californica
      nucleopolyhedrovirus chitinase is localized primarily within the endoplasmic
      reticulum (ER), which is consistent with the presence of a carboxy-terminal ER
      retention motif (KDEL). Release of chitinase into the extracellular medium
      appears to be concomitant with terminal cell lysis, rather than by active
      secretion. In this study, we have shown that mutation of the KDEL motif induces a
      partial redistribution of the chitinase at both early and late times post
      infection. Deletion of the KDEL motif or substitution with glycine residues
      allowed chitinase to move through the secretory pathway, accumulating to
      detectable levels in the extracellular medium by 24 h post-infection; more than
      48 h prior to cell lysis. Deletion of the KDEL motif did not compromise enzyme
      activity, with the modified enzyme exhibiting characteristic endo- and exo
      chitinolytic activity. Trichoplusia ni larvae infected with the modified virus
      were found to liquefy approximately 24 h earlier than larvae infected with a
      control virus in which the chitinase KDEL motif had not been deleted.

PMID- 11842264
TI  - Strain characterization of natural sheep scrapie and comparison with BSE.
AB  - Scrapie was transmitted to mice from ten sheep, collected in the UK between 1985
      and 1994. As in previous natural scrapie transmissions, the results varied
      between scrapie sources in terms of the incidence of disease, incubation periods
      and neuropathology in challenged mice. This contrasted with the uniformity seen
      in transmissions of BSE to mice. The scrapie and BSE isolates were characterized
      further by serial passage in mice. Different TSE strains were isolated from each
      source according to the Sinc or PrP genotype of the mouse used for passage. The
      same two mouse-passaged strains, 301C and 301V, were isolated from each of three
      BSE sources. Despite the variation seen in the primary transmissions of scrapie,
      relatively few mouse-passaged scrapie strains were isolated and these were
      distinct from the BSE-derived strains. The ME7 scrapie strain, which has often
      been isolated from independent sheep sources in the past, was identified in
      isolates from four of the sheep. However, a new distinct strain, 221C, was
      derived from a further four scrapie sheep. These results suggest that there is
      agent strain variation in natural scrapie in sheep and that the spectrum of
      strains present may have changed over the last 20 years. The tested sample is too
      small to come to any conclusions about whether the BSE strain is present in
      sheep, but the study provides a framework for further more extensive studies.

PMID- 11842265
TI  - Expression of doppel in the CNS of mice does not modulate transmissible
      spongiform encephalopathy disease.
AB  - Late onset ataxia reported in three independently derived PrP null lines of mice
      has been attributed to the overexpression of the doppel protein in the CNS of
      these mice rather than to the loss of PrP. The central role of PrP in the
      transmissible spongiform encephalopathies (TSEs), the proximity of the gene which
      encodes doppel (Prnd) to the PrP gene (Prnp) and the structural similarity shared
      by PrP and doppel have led to the proposition that ataxia which develops during
      TSE disease could, in part, be due to doppel. In order to address this
      hypothesis, we have crossed our two inbred lines of PrP null mice, which either
      express (RCM) or do not express (NPU) the Prnd gene in the CNS, with mice
      expressing two Prnp(a[108F189V]) alleles of the PrP gene. We have found that the
      TSE infection does not influence the level of expression of Prnd in the CNS at
      the terminal stages of disease. Moreover, we have demonstrated that the level of
      expression of Prnd in the CNS has no influence on the incubation period, vacuolar
      pathology nor amount or distribution of PrP(Sc) deposition in the brains of the
      TSE-infected mice. Doppel has therefore no apparent influence on the outcome of
      TSE disease in transgenic mice, suggesting it is unlikely to be involved in the
      naturally occurring TSE diseases in other species.

PMID- 11842266
TI  - Prion protein gene polymorphisms in natural goat scrapie.
AB  - A total of 51 goats, including seven clinical cases, from the first herd in
      Greece reported to have scrapie was examined to discern an association between
      scrapie susceptibility and polymorphisms of the gene encoding the prion protein
      (PrP). Each animal was evaluated for clinical signs of the disease,
      histopathological lesions associated with scrapie, the presence of detectable
      protease-resistant PrP in the brain and PrP genotype. Eleven different PrP
      genotypes encoding at least five unique predicted mature PrP amino acid sequences
      were found. These genotypes included the amino acid polymorphisms at codons 143
      (H-->R) and 240 (S-->P) and 'silent' nucleotide alterations at codons 42 (a-->g)
      and 138 (c-->t). Additionally, novel caprine amino acid polymorphisms were
      detected at codons 21 (V-->A), 23 (L-->P), 49 (G-->S), 154 (R-->H), 168 (P-->Q)
      and 220 (Q-->H) and new silent mutations were found at codons 107 (g-->a) and 207
      (g-->a). The following variants were found in scrapie-affected goats: VV(21),
      LL(23), GG(49,) SS(49), HH(143), HR(143), RR(154), PP(168), PP(240), SP(240) and
      SS(240). All scrapie-affected animals carried the HH(143)RR(154) genotype, with
      the exception of two goats (HR(143)), both of which had detectable protease
      resistant PrP but showed no clinical signs or histopathological lesions
      characteristic of scrapie.

PMID- 11842267
TI  - The biomechanical foundations of a safe labor environment: Bernstein's vision in
      1930.

PMID- 11842268
TI  - Changes in multi-joint performance with age.
AB  - The purpose of this study was to determine whether elderly adults exhibit
      deficits in the performance of multi-joint movements. Two groups of subjects
      (mean ages, 68.9 and 30.1 years, respectively) participated in this experiment.
      Subjects performed planar arm pointing movements to various targets. One target
      could be achieved via elbow extension only, while the remaining 3 required both
      elbow extension and horizontal shoulder flexion, thus requiring coordination at
      the 2 joints. In contrast to the young adults, the elderly adults produced
      movements that became less smooth and less accurate with increasing shoulder
      joint contribution. The results imply a selective coordination deficit for the
      elderly adults. In addition, the elderly adults coactivated opposing muscles more
      than the young adults for the single-joint movement. However, the elderly adults
      reduced coactivation at both joints for the 2-joint actions, while the young
      adults did not. These data suggest a relationship between high coactivation
      levels and good performance for elderly adults. It may be more difficult for the
      elderly to implement high coactivation levels for multi-joint movements because
      of the increased energy costs and complexity of planning required in comparison
      to the single joint actions. Thus, to achieve motor performance, elderly persons
      appear to use coactivation in a manner that is fundamentally different than young
      adults.

PMID- 11842269
TI  - Initial muscle activity in planar ballistic arm movements with varying external
      force directions.
AB  - We have investigated, in fast movements, the hypothesis that bi-articular muscles
      are preferentially selected to control the direction of force exerted on the
      environment, while mono-articular muscles are selected to control both this
      exerted force direction as well as the movement direction. Fourteen subjects
      performed ballistic arm movements involving shoulder and elbow rotations in the
      horizontal plane, either with or without an external force applied at the wrist.
      Joint torques required to counteract the external force were in the same order of
      magnitude as those required to overcome the inertial load during movements. EMG
      was recorded from mono- and bi-articular flexors and extensors of the elbow and
      shoulder. Signals were rectified and integrated (IREMG) over 100 ms following the
      first detected activity. MANOVA revealed that, contrary to the hypothesis, IREMG
      of bi-articular muscles varied with movement direction just as that of the mono
      articular muscles. It was concluded that the present data do not support the
      hypothesis mentioned above. A second finding was that movement effects on IREMG
      were much stronger than external force effects. This could not be explained using
      Hill's force-velocity relationship. It may be an indication that in the
      initiation of fast movements, IREMG is not only tuned to movement dynamics and
      muscle contractile properties, but also to the dynamics of the build up of an
      active state of the muscle.

PMID- 11842270
TI  - Three-month-old infants can select specific leg motor solutions.
AB  - In this study we used a biofeedback system to evaluate the joint movements of 3
      month-old infants in real-time. The computer was set to discriminate a specific
      leg position as the motor task infants had to discover to receive the
      reinforcement from a mobile. Two groups of infants were given two different
      tasks: (1) to cross 85  knee flexion in the flexion group, and (2) to cross 35 
      knee extension in extension group. The results from this experiment suggest that
      infants in both groups learned the task; however, they used different motor
      solutions. Infants in the flexion group demonstrated two distinctly different
      motor solutions to make the mobile move. One was movement-based and was
      characterized by an increase in kicking frequency, while the other was posture
      based. In contrast, most infants in the extension group only used the movement
      based solution to gain the reinforcements. Controlling the knee at the 35 
      extension positions seems to be more difficult than at the 85  flexion positions
      for 3-month-old infants. These results indicate that infants are capable of
      discovering narrowly defined leg motor solutions and that, depending on their
      individual characteristics and the task demands, they select different motor
      solutions.

PMID- 11842271
TI  - Effects of creatine monohydrate supplementation during combined strength and high
      intensity rowing training on performance.
AB  - This study investigated the effect of creatine monohydrate (Cr) supplementation
      on performance and training volume in rowers. Twenty-two rowers trained with
      continuous and interval rowing and resistance training 4 and 2 days/week,
      respectively, for 6 weeks. Cr supplementation consisted of a 5-day load (0.3
      g/kg(-1) x day(-1)) followed by a 5-week maintenance dose (0.03 g/kg(-1) x day(
      1)) while training. Five days of Cr loading did not change body composition,
      repeated interval rowing performance, 2,000-m rowing times, or strength
      performance. Five additional weeks of training with a maintenance dose of Cr or
      placebo significantly improved body composition, VO2max, 2,000-m rowing times,
      repeated power interval performance, and strength to a similar extent in both
      groups. Subjects training with Cr did not perform more repetitions per set of
      strength exercise nor produce or maintain higher power outputs during repeated
      rowing sessions. Cr supplementation did not increase performance or training
      volume over a placebo condition in rowers that performed a combined high
      intensity rowing and strength program.

PMID- 11842272
TI  - Evaluation of the Monark Wingate ergometer by direct measurement of resistance
      and velocity.
AB  - The purpose of this study was to assess the accuracy of the new basket-loaded
      Wingate ergometer introduced by Monark (Model 834E). Velocity was measured
      directly from the pedal switch while tension was measured with transducers on
      each end of the brake lacing. Moment of inertia of the flywheel was determined
      and accounted for in the calculation of power. Constant load tests (39.24 to 98.1
      N), were done at pedaling speeds from 80 to 140 r x min(-1) (flywheel angular
      velocity = 30-50 rad x s(-1)). The load transmitted to the lacing at the front
      and back of the flywheel was 95.5 +/- 0.8% (mean +/- SEM) and 6.71 +/- 0.8%,
      respectively, of the load in the basket. Thus, the resultant tension (front minus
      back) was on average 88.8 +/- 0.57% of the applied load. The velocity recorded by
      the Monark Wingate Ergometer computer program (MWECP) was the same (100.4 +/-
      1.56%) as that determined from the pedal switch directly. Five male mountain
      bikers performed a 30-s all-out test. Peak power calculated by MWECP (1181 +/-
      55W) was always higher (p < .01) than that calculated from direct measures of
      tension and velocity (1102 +/- 66W), when not taking into account the moment of
      inertia. These experiments suggest that the basket-loaded Monark Wingate
      ergometer does not provide a correct calculation of power because of incomplete
      load transmission to the flywheel.

PMID- 11842273
TI  - Pulmonary responses during the cycle-run succession in elite and competitive
      triathletes.
AB  - OBJECTIVES: The purpose of this study was to determine the effect of performance
      level on the pulmonary responses in triathletes during the cycle-run succession.
      METHODS: Eight regionally and nationally ranked (Competitive) and six
      internationally ranked (Elite) male triathletes underwent 30 min of cycling
      followed by 20 min of running (C-R) and 30 min of control cycling (C). Before and
      10 min after each trial, the triathletes underwent lung function testing.
      Ventilatory data were collected every minute using an automated breath-by-breath
      system. RESULTS: The results showed that (a) cycling induced a significant
      increase in residual volume and functional residual capacity in the Elite group
      (P <.05); (b) although cycling induced a significant decrease in DLCO in both
      groups, this decrease persisted at the end of the cycle-run exercise in the
      Competitive group only (P <.05); and (c) the rise in breathing frequency was
      significantly greater in the Competitive triathletes during the first 8 min of
      the subsequent run (P <.04). CONCLUSIONS: We conclude that the internationally
      ranked--or elite-performance--triathletes may have developed specific responses
      to the cycle-run succession.

PMID- 11842274
TI  - Hormone responses to resistance vs. endurance exercise in premenopausal females.
AB  - Sixteen, cross-trained, premenopausal women participated in an endurance,
      resistance, and control session to compare hormone responses. The resistance
      session included 3 sets of eight exercises at 10 RM intensity. The endurance
      session consisted of a 40-min cycling protocol at 75% of maximal heart rate.
      During the control session, subjects rested for 35 min. Serum DHEA, estradiol,
      testosterone, growth hormone, IGF-I, cortisol, and plasma lactate concentrations
      were measured pre-exercise, post-exercise, and 30 min into recovery. Differences
      in intensity variables existed between the three sessions. Endurance exercise
      elicited increases in growth hormone, estradiol, and testosterone compared to the
      control session, and growth hormone increased after the resistance compared to
      the control session. The exercise protocols used in this study indicate that an
      acute bout of exercise can stimulate the endocrine system in premenopausal
      females. In addition, these results indicate that differences exist between these
      two exercise protocols when compared to a control session.

PMID- 11842275
TI  - Muscle protein metabolism in the elderly: influence of exercise and nutrition.
AB  - Although the causes of sarcopenia are multi-factorial, at least some, such as
      poor nutrition and inactivity, may be preventable. Changes in muscle mass must be
      a result of net muscle protein breakdown over that particular time period. Stable
      isotope methodology has been used to examine the metabolic basis of muscle loss.
      Net muscle protein breakdown may occur due to a decrease in the basal level of
      muscle protein synthesis. However, changes of this type would likely be of small
      magnitude and undetectable by current methodology. Hormonal mediators may also be
      important, especially in association with forced inactivity. Net muscle protein
      breakdown may be also attributed to alterations in the periods of net muscle
      protein synthesis and breakdown each day. Reduced activity, combined with
      ineffectual nutrient intake, could lead to decreased net muscle protein balance.
      Chronic resistance exercise training clearly is an effective means of increasing
      muscle mass and strength in elderly individuals. Although sometimes limited,
      acute metabolic studies provide valuable information for maintenance of muscle
      mass with age.

PMID- 11842276
TI  - Effects of very long (up to 10 years) proton pump blockade on human gastric
      mucosa.
AB  - BACKGROUND: Long-term use of proton pump inhibitors (PPI) has been reported to
      worsen oxyntic mucosa gastritis and the resulting gland atrophy has been
      considered a potential risk factor for neoplastic changes in the gastric mucosa.
      AIMS: The present study examines the effect of extended continuous PPI treatment
      for up to 10 years on the exocrine and endocrine stomach of patients with acid
      related diseases of the upper GI tract. METHODS: Biopsies from the antral and
      oxyntic mucosa taken at regular time intervals were examined for gastritis,
      atrophy, intestinal metaplasia, Helicobacter pylori and argyrophil cells and
      correlated to serum gastrin levels. RESULTS: A general amelioration of antral
      gastritis without relevant changes of atrophy or intestinal metaplasia,
      contrasted with the worsening of gastritis and gland atrophy seen in the oxyntic
      mucosa of reflux esophagitis (but not gastric or duodenal ulcer) patients in the
      presence of H. pylori infection. In association with PPI- induced
      hypergastrinemia, argyrophil cell hyperplasia (but not dysplasia or neoplasia)
      developed in the oxyntic mucosa. CONCLUSION: The present results outline the
      milder pretreatment pattern and higher proneness to PPI-related, H. pylori
      restricted worsening of oxyntic mucosa gastritis in reflux esophagitis compared
      to gastric ulcer or duodenal ulcer patients. In addition, they confirm a
      substantial safety of long-term PPI therapy as concerns neoplastic changes in the
      exocrine and endocrine human stomach.

PMID- 11842277
TI  - Less damaging effect of whisky in rat stomachs in comparison with pure ethanol.
      Role of ellagic acid, the nonalcoholic component.
AB  - BACKGROUND/AIM: Ellagic acid (EA), one of the polyphenols that are abundantly
      contained in whisky as a nonalcoholic component, has antioxidant and anti
      inflammatory activities. In the present study, we compared the action of whisky
      and pure ethanol on the rat gastric mucosa, and examined the role of EA in the
      less-damaging effect of whisky in the stomach. METHODS: Under urethane
      anesthesia, a rat stomach was mounted in an ex vivo chamber, perfused with
      saline, and the transmucosal potential difference (PD) was measured before and
      after exposure to whisky (Yamazaki, Suntory) and ethanol (43%). In a separate
      study, the animals were given whisky or ethanol (1 ml, 43%) p.o. under
      unanesthetized conditions, killed 1 h later, and the gastric mucosa was examined
      for hemorrhagic lesions. RESULTS: Both whisky and ethanol caused a PD reduction,
      resulting in damage in the stomach, but these responses were less marked in the
      case of whisky. Although the reduced PD recovered gradually after removal of
      ethanol, this process was significantly expedited by co-application of EA (80
      microg/ml), the recovery rate being much the same as that observed after exposure
      to whisky. The less-damaging effect of whisky was confirmed in unanesthetized
      rats after p.o. administration of these agents. In addition, EA (1-30 mg/kg),
      administered p.o. together with absolute ethanol (99.9%), reduced the severity of
      gastric lesions induced by ethanol, in a dose-dependent manner, and the effect at
      30 mg/kg was equivalent to that obtained by the whisky component containing
      several low- and high-molecular-weight polyphenols. EA had a scavenging action
      against both oxygen and hydroxyl radicals in vitro, the effect being equivalent
      to that of catechol or alpha-tocopherol. CONCLUSION: These results suggest that
      whisky is less irritating to the gastric mucosa, as compared with pure ethanol,
      and this property of whisky may be explained by EA, one of polyphenols contained
      in whisky, and its radical scavenging action.

PMID- 11842278
TI  - Second-line Helicobacter pylori eradication with a furazolidone-based regimen in
      patients who have failed a metronidazole-based regimen.
AB  - BACKGROUND/AIM: In developing countries the standard quadruple therapy containing
      metronidazole results in suboptimal eradication rates of Helicobacter pylori
      (<75%). In a retrospective study, we undertook to evaluate efficacy and
      tolerability of a furazolidone-based regimen (omeprazole, furazolidone, bismuth,
      and tetracycline) in patients who had previously failed the standard
      metronidazole-based regimen (omeprazole, metronidazole, bismuth, and
      amoxicillin). METHODS: The records of H. pylori infected patients who were
      referred to outpatient clinic (from March 1999 to August 1999) and who underwent
      previous eradication regimens were studied. A total of 320 cases were noted to
      have received a metronidazole-based quadruple regimen. From these 320 patients,
      80 were noted to have failed this regimen based on a urea breath test. These 80
      patients were enrolled in the study and given the furazolidone-based regimen.
      Side effects were assessed at follow-up visits. At least 2 months after the end
      of each therapy regimen, a (14)C-urea test was performed in each subject to
      document the cure of the patients. RESULTS: A total of 80 patients (39 males and
      41 females) with a mean age of 43.8 +/- (SD) 13.3 years were studied. The H.
      pylori eradication rate was 90% with the furazolidone-based regimen. The side
      effects of this regimen were minor. CONCLUSIONS: A furazolidone-based regimen is
      effective in patients who do not achieve cure of H. pylori infection with the
      metronidazole-based quadruple therapy. In areas where the metronidazole
      resistance is high, initial therapy with a furazolidone-based regimen is
      recommended.

PMID- 11842279
TI  - R116C mutation of cationic trypsinogen in a Turkish family with recurrent
      pancreatitis illustrates genetic microheterogeneity of hereditary pancreatitis.
AB  - Hereditary pancreatitis is due to heterozygosity for gain-of-function mutations
      in the cationic trypsinogen gene which result in increased levels of active
      trypsin within pancreatic acinar cells and autodigestion of the pancreas. The
      number of disease-causing defects is generally considered to be low. To gain
      further insight into the molecular basis of this disorder, DNA sequence analysis
      of all five exons was performed in 109 unrelated patients with idiopathic chronic
      pancreatitis in order to determine the variability of the underlying mutations.
      Two German females and one German male were carriers of the most common N29I and
      R122H mutations (trypsinogen numbering system). In a Turkish proband, an arginine
      (CGT) to cysteine (TGT) substitution at amino acid position 116 was identified.
      Family screening demonstrated that the patient had inherited the mutation from
      his asymptomatic father and that he had transmitted it to both of his children,
      his daughter being symptomatic since the age of 3 years. In addition, a German
      male was found to be a heterozygote for a D100H (GAC-->CAC) amino acid
      replacement. Our data provide evidence for genetic heterogeneity of hereditary
      pancreatitis. The growing number of cationic trypsinogen mutations is expected to
      change current mutation screening practices for this disease.

PMID- 11842281
TI  - Cyclooxygenase 2 expression in chronic pancreatitis: correlation with stage of
      the disease and diabetes mellitus.
AB  - BACKGROUND: Fibrotic replacement of the exocrine pancreatic parenchyma and
      infiltration of inflammatory cells are the main characteristics of chronic
      pancreatitis (CP). Inflammation involves prostaglandin production in numerous
      inflammatory and noninflammatory cells, and cyclooxygenase 2 (COX-2) is the
      dominant regulator of prostaglandin synthesis. AIMS: In the present study, we
      analyzed the expression of COX-2, the key enzyme for prostaglandin synthesis in
      pancreatic tissues, and evaluated its relation to exocrine and endocrine tissue
      alterations in CP. PATIENTS AND METHODS: Pancreatic tissue specimens from 27
      patients undergoing pancreatic head resection for CP were included in the study.
      Pancreatic tissues from 14 organ donors served as controls. The tissue specimens
      were analyzed histopathologically and for COX-2 immunoreactivity. RESULTS: In
      normal pancreatic tissue samples, COX-2 immunoreactivity was restricted to islet
      cells. In contrast, in early-stage CP, islets as well as ductal cells showed
      intense COX-2 immunoreactivity. In advanced-stage CP, ductal cells were still
      strongly positive for COX-2, yet islets displayed a variable COX-2 staining
      pattern which was associated with the distribution of insulin-positive cells and
      with the clinical diabetes mellitus status of the patient. Thus, patients with
      normal or latent diabetes mellitus status showed COX-2 immunoreactivity, whereas
      in diabetic patients the COX-2 immunoreactivity was decreased or absent in
      pancreatic islets. CONCLUSION: The presence of COX-2 in ductal cells of early and
      advanced CP, the relationship between COX-2 and insulin expression in the islets,
      and the diabetes mellitus status of CP patients suggest that this enzyme plays a
      role in the pathogenesis of exocrine and endocrine damage in CP.

PMID- 11842280
TI  - Pancreatitis-associated protein (HIP/PAP) gene expression is upregulated in NOD
      mice pancreas and localized in exocrine tissue during diabetes.
AB  - We have previously shown a specific significant overexpression in the exocrine
      pancreatic tissue of two members of the regenerating gene multifamily: reg I and
      reg II in the non-obese diabetic (NOD) mouse during active diabetogenesis. To
      strengthen the hypothesis that the overexpression of these genes may represent a
      defence of the acinar cell against pancreatic endocrine agression, we studied the
      pancreatic expression and the localization of another member of this family: the
      pancreatitis-associated protein (PAP) in NOD mice under the same conditions. We
      found that NOD mice present significantly higher PAP mRNA levels than control
      IOPS-OF1 mice. There is no difference between female NOD mice which progressively
      develop type I diabetes between 100 and 200 days and male NOD mice which are
      protected. The only difference observed was in function of the age of onset of
      diabetes. Before 180 days, the PAP mRNA levels were similar to those found in NOD
      males and nondiabetic females, but above 180 days the levels of PAP mRNA
      increased significantly. More importantly immunohistological studies demonstrate
      a striking difference in the protein localization between normal or nondiabetic
      NOD mice and diabetic NOD mice. If the protein is mainly detected in the islet
      cells in the absence of diabetes, a specific and intense expression of PAP was
      observed in the acinar cells of diabetic NOD mice. In conclusion, our data
      demonstrates that the acinar cells may react to a long-lasting pancreatic
      endocrine aggression by an induction of PAP and underlines the existence of a
      symbiotic relationship between endocrine and exocrine tissue.

PMID- 11842282
TI  - Germinated barley foodstuff exhibits different adsorption properties for
      hydrophilic versus hydrophobic bile acids.
AB  - BACKGROUND/AIMS: Germinated barley foodstuff (GBF), a type of dietary fiber,
      exhibits therapeutic effects in ulcerative colitis (UC) patients. However, the
      precise mechanisms responsible for these effects are still under investigation.
      On the other hand, it has been suggested that bile salts in the gut lumen play an
      important role in the integrity of the intestinal mucosa. The aim of the present
      study was to investigate the ability of GBF to adsorb bile salts in vitro.
      METHODS: The binding capacities of GBF, enzymatically digested GBF (GBF-fiber),
      and alpha-cellulose for unconjugated and conjugated bile salts were measured
      using Langmuir's method. The morphology of these fibers was observed by light and
      fluorescence microscopy. RESULTS: GBF adsorbed bile salts very strongly,
      especially hydrophobic bile salts. Even after enzymatic digestion, the GBF fiber
      still exhibited strong binding capacity, whereas alpha-cellulose exhibited very
      low binding capacity. Microscopically, GBF consists mainly of aleurone, a lattice
      like cell wall with cytoplasm enclosed. After enzymatic digestion, the cytoplasm
      was also digested. CONCLUSION: GBF possesses a great capacity to adsorb bile
      salts. This may be part of the mechanism for the therapeutic effects of GBF in UC
      patients.

PMID- 11842283
TI  - An unusual metastatic motilin-secreting neuroendocrine tumour with a 20-year
      survival. Pathological, biochemical and motility features.
AB  - Motilin-secreting neuroendocrine tumours have been rarely described.
      Immunohistochemical, biochemical and motility investigations were performed in a
      62-year-old man with liver and bone metastases of a motilin-secreting
      neuroendocrine tumour originating from a rectal polyp removed 14 years
      previously. Symptoms related to liver metastases were reduced by a right
      hepatectomy whereas plasma motilin levels were decreased. The patient also
      underwent two operations for spinal cord decompression and survived 6 more years
      under medical treatment, mainly octreotide. Immunohistochemistry revealed
      predominant expression of motilin-containing cells, with rare cells expressing
      somatostatin and pancreatic polypeptide, and staining for only one panendocrine
      marker, neurone-specific enolase. A liver tumour extract contained 17.9 microg
      motilin per gram of tissue, which permitted to isolate and characterize human
      motilin, which was identical to porcine motilin. Plasma column gel chromatography
      revealed a main peak corresponding apparently to porcine motilin. The patient had
      no symptoms of disturbed motility. Gastric emptying and gastroduodenojejunal
      motility were found within normal limits. The absence of alterations of gut
      motility was perhaps related to sustained autonomous motilin production. The long
      evolution of this type of tumour suggests that plasma motilin determination
      should be added to the investigations for neuroendocrine tumours.

PMID- 11842284
TI  - The long-term efficacy of the intrahepatic portosystemic shunt (TIPS) for the
      treatment of bleeding anorectal varices in cirrhosis. A case report and review of
      the literature.
AB  - BACKGROUND: In patients with portal hypertension and variceal hemorrhage, the
      transjugular intrahepatic portosystemic shunt (TIPS) is indicated when drug
      therapy or endoscopic treatment fails to control bleeding. Ruptured esophageal or
      gastric varices are the most frequent causes of portal hypertension-related
      hemorrhage, but anorectal varices may also bleed. Although several case reports
      have proposed TIPS in this situation, the long-term results of this procedure
      have not been described. METHODS: We report here the case of a 68-year-old
      patient with decompensated cirrhosis who presented with recurrent hematochezia
      due to anorectal varices. RESULTS: A successful control of bleeding could be
      obtained after placement of TIPS. After 3 years of follow-up, rectal bleeding did
      not recur, the shunt remained primarily patent, and the patient did not present
      overt hepatic encephalopathy. CONCLUSION: TIPS procedure should be considered as
      an effective treatment of recurrent bleeding from anorectal varices in patients
      with decompensated cirrhosis.

PMID- 11842286
TI  - The Melbourne Asthma Study: 1964-1999.
AB  - A group of children with a past history of wheezing was randomly selected from
      the Melbourne community at the age of 7 years in 1964, and a further group of
      children with severe wheezing was selected from the same birth cohort at the age
      of 10 years. These subjects have been followed prospectively at 7-year intervals,
      with the last review in 1999, when their average age was 42 years. Eighty-seven
      percent of the original cohort who were still alive participated in the 1999
      review. This study showed that the majority of children who had only a few
      episodes of wheezing associated with symptoms of a respiratory infection had a
      benign course, with many ceasing to wheeze by adult life. Most who continued with
      symptoms into adult life were little troubled by them. Conversely, those children
      with asthma mostly continued with significant wheezing into adult life, and the
      more troubled they were in childhood, the more likely symptoms continued. There
      was a loss in lung function by the age of 14 years in those with severe asthma,
      but the loss did not progress in adult life. The childhood asthma had been
      treated before the availability of inhaled steroids. There was no significant
      loss of lung function in those with milder symptoms.

PMID- 11842287
TI  - Pathways for bradykinin formation and inflammatory disease.
AB  - Bradykinin is formed by the interaction of factor XII, prekallikrein, and high
      molecular-weight kininogen on negatively charged inorganic surfaces (silicates,
      urate, and pyrophosphate) or macromolecular organic surfaces (heparin, other
      mucopolysaccharides, and sulfatides) or on assembly along the surface of cells.
      Catalysis along the cell surface requires zinc-dependent binding of factor XII
      and high-molecular-weight kininogen to proteins, such as the receptor for the
      globular heads of the C1q subcomponent of complement, cytokeratin 1, and
      urokinase plasminogen activator receptor. These 3 proteins complex together
      within the cell membrane, and initiation depends on autoactivation of factor XII
      on binding to gC1qR (the receptor for the globular heads of the C1q subcomponent
      of complement). There is also a factor XII-independent bypass mechanism requiring
      a cell-derived cofactor or protease that activates prekallikrein. Bradykinin is
      degraded by carboxypeptidase N and angiotensin-converting enzyme. Angioedema that
      is bradykinin dependent results from hereditary or acquired C1 inhibitor
      deficiencies or use of angiotensin-converting enzyme inhibitors to treat
      hypertension, heart failure, diabetes, or scleroderma. The role for bradykinin in
      allergic rhinitis, asthma, and anaphylaxis is to contribute to tissue
      hyperresponsiveness, local inflammation, and hypotension. Activation of the
      plasma cascade occurs as a result of heparin release and endothelial-cell
      activation and as a secondary event caused by other pathways of inflammation.

PMID- 11842288
TI  - Asthma biomarkers and drug trials.

PMID- 11842289
TI  - Bioterrorism: relevance to allergy and immunology in clinical practice.
AB  - It has become clear in recent months that the threat of bioterrorism is very
      real. All physicians need to be aware of the presenting signs and symptoms of the
      most likely agents. Allergists and immunologists care for a unique population of
      patients with several alterations of their immune system that might change the
      expected course of illnesses from biologic terror agents. In this review, we
      discuss specific bioterrorism agents, focusing on their presentation,
      pathogenesis, and immunology. In addition, we describe how these illnesses might
      differ in the population of patients followed by allergists and immunologists.

PMID- 11842290
TI  - Reducing disparities in asthma care: priorities for research--National Heart,
      Lung, and Blood Institute workshop report.
AB  - Minority groups with diverse racial and ethnic heritages and persons living in
      poverty are much more likely to die of asthma and to require emergency care for
      exacerbations of asthma than white persons not living in poverty. The National
      Heart, Lung, and Blood Institute convened a multidisciplinary group of expert
      scientists and clinicians to review current research aimed at understanding risk
      factors for these disparities in asthma health outcomes, to describe key barriers
      to improving asthma outcomes, and to establish priorities for future research.
      Education programs for asthma and other chronic diseases were reviewed.
      Successful elements of clinic and community-based programs were identified.
      Factors potentially involved in producing disparities include gene-environment
      interaction, psychologic and social factors, and socioeconomic status. Stress
      potentially contributes to asthma morbidity at both the individual and community
      level. Recommendations are made to stimulate research to understand risk factors
      for disparities and their mechanisms (e.g., gene-by-environment interactions and
      the role of stress), to define appropriate research designs and methods for
      evaluating behavioral and community interventions, and to examine how
      differential access to care contributes to morbidity. Research is encouraged to
      identify strategies that improve cultural adaptation and adoption of proven
      programs in a variety of populations.

PMID- 11842291
TI  - Histone deacetylation inhibits IL4 gene expression in T cells.
AB  - BACKGROUND: Dysregulated expression of IL-4 has been linked with allergic
      diseases. IL-4 expression is controlled at the level of gene transcription by the
      coordinated action of multiple factors that bind regulatory promoter elements. In
      addition, alterations in chromatin structure are thought to play a role in
      regulating the expression of cytokines in the T(H)2 gene cluster, although the
      biochemical basis for these alterations in human T cells is not well understood.
      OBJECTIVE: We sought to define the role of histone acetylation in the regulation
      of IL4 gene expression in human T cells. METHODS: IL-4 protein production was
      measured by means of ELISA. IL-4 promoter activity was measured with luciferase
      based reporter constructs transiently transfected into Jurkat T cells. The
      acetylation status of histones associated with the IL4 gene was analyzed with
      chromatin immunoprecipitation assays. RESULTS: IL-4 production from activated
      peripheral blood T cells was enhanced by the histone deacetylase inhibitor
      trichostatin A. Overexpression of the type 1 histone deacetylases 1, 2, and 3
      inhibited transcription driven by the IL-4 promoter in Jurkat T cells, whereas
      cotransfection of the histone acetyltransferase CREB-binding protein potentiated
      IL-4 promoter activity. Using chromatin immunoprecipitation assays, we show that
      nucleosomes in the proximal IL-4 promoter are acetylated on T-cell activation.
      CONCLUSION: Our results demonstrate that the acetylation state of histones
      associated with the IL-4 promoter is a key regulator of IL4 gene expression.

PMID- 11842292
TI  - A calcium-activated chloride channel (HCLCA1) is strongly related to IL-9
      expression and mucus production in bronchial epithelium of patients with asthma.
AB  - BACKGROUND: One of the cardinal features of airway remodeling in asthma is mucus
      gland hyperplasia and mucus overproduction and hypersecretion. Recently, a
      calcium-activated chloride channel, HCLCA1, was described that is upregulated by
      IL-9 and thought to regulate the expression of soluble gel-forming mucins, such
      as MUC5A/C, a critical component of mucus in the airways. OBJECTIVE: We sought to
      examine the expression of HCLCA1 in bronchial biopsy specimens of asthmatic
      subjects compared with those of control subjects and to demonstrate its
      relationship with IL-9, IL-9 receptor (IL-9R), and markers of mucus production.
      METHODS: Bronchial biopsy specimens from asthmatic (n = 9) and control (n = 10)
      subjects were stained with periodic acid-Schiff to identify mucus
      glycoconjugates. IL-9- and IL-9R-positive cells were identified with
      immunocytochemistry, and HCLCA1 expression was detected by means of in situ
      hybridization with cRNA probes. RESULTS: We demonstrate significant increases in
      IL-9 (P <.001) and IL-9R (P <.05) immunoreactivity, as well as increased
      expression of HCLCA1 mRNA (P <.001), in the epithelium of asthmatic patients
      compared with that found in control subjects. There was also an increase in the
      number of mucusproducing cells in biopsy specimens from asthmatic subjects (P
      <.001). HCLCA1 mRNA was strongly and selectively colocalized with periodic acid
      Schiff and IL-9R-positive epithelial cells. In particular, a strong positive
      correlation was observed between HCLCA1 mRNA expression and IL-9-positive (r =
      0.69, P < 0.01) or IL9R-positive (r = 0.79, P <.01) cells. CONCLUSION: An
      upregulation of HCLCA1 in the IL-9- responsive mucus-producing epithelium of
      asthmatic subjects compared with that seen in control subjects supports the
      hypothesis that this channel may be responsible, in part, for the overproduction
      of mucus in asthmatic subjects. These preliminary findings suggest the inhibition
      of HCLCA1 may be an important new therapeutic approach to control mucus
      overproduction in chronic airway disorders.

PMID- 11842293
TI  - Pollen immunotherapy reduces the development of asthma in children with seasonal
      rhinoconjunctivitis (the PAT-study).
AB  - BACKGROUND: Children with allergic rhinitis are likely to develop asthma.
      OBJECTIVE: The purpose of this investigation was to determine whether specific
      immunotherapy can prevent the development of asthma and reduce bronchial
      hyperresponsiveness in children with seasonal allergic rhinoconjunctivitis.
      METHODS: From 6 pediatric allergy centers, 205 children aged 6 to 14 years (mean
      age, 10.7 years) with grass and/or birch pollen allergy but without any other
      clinically important allergy were randomized either to receive specific
      immunotherapy for 3 years or to an open control group. All subjects had moderate
      to severe hay fever symptoms, but at inclusion none reported asthma with need of
      daily treatment. Symptomatic treatment was limited to loratadine, levocabastine,
      sodium cromoglycate, and nasal budesonide. Asthma was evaluated clinically and by
      peak flow. Methacholine bronchial provocation tests were carried out during the
      season(s) and during the winter. RESULTS: Before the start of immunotherapy, 20%
      of the children had mild asthma symptoms during the pollen season(s). Among those
      without asthma, the actively treated children had significantly fewer asthma
      symptoms after 3 years as evaluated by clinical diagnosis (odds ratio, 2.52; P
      <.05). Methacholine bronchial provocation test results improved significant in
      the active group (P <.05). CONCLUSION: Immunotherapy can reduce the development
      of asthma in children with seasonal rhinoconjunctivitis.

PMID- 11842295
TI  - Direct and indirect costs of asthma to an employer.
AB  - BACKGROUND: Asthma is a chronic inflammatory condition of the airways that has a
      significant effect on the use of health care resources. OBJECTIVE: This study is
      the first of its kind to estimate the overall cost of asthma to a major employer
      in the United States and to profile the nature of the asthma expenses. METHODS:
      The annual per capita cost of asthma was determined for beneficiaries of a major
      employer by analyzing medical, pharmaceutical, and disability claims data. The
      incremental cost of asthma was determined by using a case-control method matching
      asthmatic patients to individuals with no record of asthma treatment. RESULTS:
      The use of health care services, as well as the rate of disability, was
      substantially higher among asthmatic patients than among control subjects. Annual
      per capita employer expenditures for asthmatic patients were approximately 2.5
      times those for control subjects ($5385 vs. $2121, respectively). Among asthmatic
      employees with disability claims, total costs were approximately 3 times higher
      than those among disability claimants in the employee control sample ($14,827 vs.
      $5280). For asthmatic employees, wage-replacement costs for workdays lost as a
      result of disability and sporadic absenteeism (40%) accounted for almost as much
      as did medical care (43%). CONCLUSION: Failure to account fully for the broader
      consequences of asthma in terms of indirect and comorbid treatment costs would
      result in a significant underassessment of the cost of asthma to an employer.

PMID- 11842294
TI  - A randomized, double-blind trial of the effect of treatment with montelukast on
      bronchial hyperresponsiveness and serum eosinophilic cationic protein (ECP),
      soluble interleukin 2 receptor (sIL-2R), IL-4, and soluble intercellular adhesion
      molecule 1 (sICAM-1) in children with asthma.
AB  - BACKGROUND: Anti-inflammatory properties of leukotriene modifiers and their
      effect on bronchial hyperresponsiveness have not been studied in children with
      asthma. OBJECTIVE: The primary objective of this study was to determine the
      changes in serum levels of inflammatory mediators, clinical efficacy, and
      bronchial hyperresponsiveness after treatment with montelukast. METHODS: In this
      double-blind, randomized, placebo-controlled trial, 39 children with mild-to
      moderate atopic asthma were randomly allocated to receive montelukast or placebo
      for 6 weeks. Main outcome measures were changes in serum concentrations of
      soluble interleukin 2 receptor (sIL-2R), IL-4, and soluble intercellular adhesion
      molecule 1 (sICAM-1); peripheral blood eosinophil count; and eosinophilic
      cationic protein (ECP). Asthma severity score, FEV(1), and bronchial
      hyperreactivity (BHR) for histamine were secondary end points. RESULTS: Compared
      to placebo, serum concentrations of IL-4, sICAM-1, and ECP and eosinophil blood
      counts significantly decreased after 6 weeks of treatment with montelukast.
      Montelukast significantly improved asthma control and FEV(1). Montelukast
      resulted in within-group significant decrease in levels of serum sIL-2R (611 vs.
      483 pg/mL), IL-4 (0.123 vs 0.102 pg/mL), sICAM-1 (280 vs. 244 ng/mL), and ECP (74
      vs. 59 microg/mL) and in eosinophil blood counts (349 vs. 310 cells/mm(3)). Mean
      FEV(1) value changed from 85% of predicted to 95% (P <.001) and for histamine
      (PC(20)H) from 2.8 mg/mL to 3.8 mg/mL (P <.001) after treatment with montelukast.
      There was no significant difference between montelukast and placebo recipients in
      the serum concentrations of sIL-2R and PC(20)H after treatment. CONCLUSION:
      Montelukast provides clinical benefit to patients with chronic asthma and
      decreases bronchial hyperresponsiveness. Montelukast caused a statistically
      significant decrease of serum concentrations in cytokine, ICAM-1, and ECP and
      peripheral blood eosinophil counts over the 6-week treatment period. This
      observation raises the possibility that leukotriene receptor antagonists, such as
      montelukast, may have effects on parameters of asthmatic inflammation.

PMID- 11842296
TI  - Array-based diagnostic gene-expression score for atopy and asthma.
AB  - Whether gene expression is useful in discriminating different atopic phenotypes
      is unclear. The aim of the study was to evaluate a gene-expression score for the
      diagnosis of atopy and asthma and to assess disease activity as a guide for
      therapeutic decisions. Purified mRNA from PBMCs of 18 atopic asthmatic subjects,
      8 atopic nonasthmatic subjects, and 14 healthy control subjects was hybridized to
      cDNA membranes. A composite atopy gene expression (CAGE) score was determined by
      using 10 genes dysregulated in atopic individuals according to a specific
      algorithm. The CAGE score was better than total IgE in differentiating atopic
      from nonatopic subjects (sensitivity, 96%; specificity, 92%). Correlation between
      the CAGE score and total IgE (P <.001) was found, and there was a trend for
      correlation with asthma severity (P =.051). The CAGE score was able to quantify
      phenotype-specific alteration in gene expression of atopic individuals. The CAGE
      score might be used as a diagnostic tool or to monitor the effects and side
      effects of therapy.

PMID- 11842297
TI  - Efficacy of combination treatment with anti-IgE plus specific immunotherapy in
      polysensitized children and adolescents with seasonal allergic rhinitis.
AB  - BACKGROUND: Specific immunotherapy (SIT) and treatment with monoclonal anti-IgE
      antibody have complementary modes of action. OBJECTIVE: The purpose of this study
      was to determine whether combined therapy could provide better efficacy than
      either treatment alone. METHODS: We conducted a randomized, double-blinded trial
      to assess the efficacy and safety of subcutaneously administered anti-IgE
      (omalizumab) or placebo in children and adolescents with seasonal allergic
      rhinitis in both a birch pollen season and a grass pollen season (sequential
      seasons together lasting an average of 84 days). There were 4 treatment arms.
      Each subject was started on SIT-birch or SIT-grass, and anti-IgE or placebo was
      started before and maintained during the anticipated pollen seasons (a total of
      24 weeks). The primary efficacy variable was symptom load, the sum of daily
      symptom severity score plus rescue medication use. RESULTS: A total of 221
      subjects (intent-to-treat population) aged 6 to 17 years were analyzed for
      efficacy. Combination therapy reduced symptom load over the 2 pollen seasons by
      48% (P <.001) over SIT alone. When analyzed separately by season, the 2 groups
      receiving unrelated SIT were considered placebo controls. In the grass season,
      symptom loads were as follows: unrelated (birch) SIT + placebo, 0.89 (reference
      value); unrelated (birch) SIT + anti-IgE, 0.49 (-45%); SIT-grass + placebo, 0.61
      (-32%); SIT-grass + anti-IgE, 0.26 (-71%). CONCLUSION: Anti-IgE therapy conferred
      a protective effect independent of the type of allergen. Additional clinical
      benefit was demonstrated in both pollen seasons, whether there was coverage by
      SIT or not. This combination might prove useful for the treatment of allergic
      rhinitis, particularly for polysensitized patients.

PMID- 11842298
TI  - IL-10 production in circulating T cells differs between allergen-induced isolated
      early and dual asthmatic responders.
AB  - BACKGROUND: IL-10 is an anti-inflammatory cytokine released from various cells,
      including T cells. The role of IL-10 in asthma pathogenesis remains uncertain.
      Allergen inhalation by atopic asthmatic subjects results in 2 bronchoconstrictor
      phenotypes: isolated early response and dual response. Persistence of allergen
      induced airway inflammation is a feature of dual responders. OBJECTIVES: The
      kinetics of IL-10 production in circulating T cells were investigated to examine
      a potential role of IL-10 in allergen-induced responses and airway inflammation.
      METHODS: Fourteen subjects with mild asthma (7 isolated early and 7 dual
      responders) were challenged with allergen. PBMCs taken before and 24 hours after
      allergen challenge were processed for intracellular IL-10 staining with
      fluorescent-conjugated anti-IL-10 antibody. The frequency of IL-10-producing
      cells was assessed for CD4(+) and CD8(+) T-cell subsets by using flow cytometry.
      RESULTS: Before allergen administration, the frequency of IL-10-producing CD4(+)
      cells was significantly higher in dual than in isolated early responders. IL-10
      producing CD4(+) cells significantly increased after allergen in early
      responders, whereas IL-10-producing CD4(+) cells significantly decreased in dual
      responders. Simultaneous assessments of IL-5-producing T cells did not show any
      differences between each group before or after allergen administration.
      CONCLUSIONS: These results suggest that the contrasting profiles of IL-10
      production may be associated with the different time course of allergen-induced
      airway inflammation between allergen-induced early and dual responders.

PMID- 11842299
TI  - Characterization of mast-cell tryptase-expressing peripheral blood cells as
      basophils.
AB  - BACKGROUND: Mast-cell tryptase is a protease with proinflammatory activity, the
      expression of which by peripheral blood leukocytes (PBLs) has not been fully
      characterized. OBJECTIVE: We examined tryptase expression in human PBLs to
      further characterize this tryptase-expressing cell population for lineage and
      disease association. METHODS: PBLs were fixed, permeabilized, stained with
      antibodies to tryptase and a panel of mast cell- and basophil-specific markers,
      and analyzed by means of flow cytometry. RESULTS: Tryptase expression was
      restricted to a population of cells that stained positive for IgE and negative
      for the panel of lineage markers (IgE(+), lin(-)). This IgE(+), lin(-) population
      did not stain for the mast-cell markers Kit or chymase but did stain for the
      basophil-specific granule proteins recognized by the 2D7 and BB1 mAbs. Per-cell
      tryptase expression demonstrated a greater than 100-fold range of expression
      among donors but did not correlate with disease status (asthma or mastocytosis),
      FEV(1), or serum tryptase concentration. Tryptase was released by purified
      basophils after anti-IgE activation. CONCLUSIONS: The phenotype of tryptase
      expressing PBLs and their lack of increase in patients with mastocytosis
      demonstrates that these cells are basophils. Per-cell basophil tryptase
      expression is highly variable between donors, with some donors expressing levels
      approaching those of mast cells. As such, anti-tryptase antibodies cannot be used
      to distinguish these 2 cell types from one another by means of flow cytometry.
      These results demonstrate that tryptase represents an additional mediator through
      which basophils may contribute to allergic inflammation.

PMID- 11842300
TI  - Intracellular IL-5 and T-lymphocyte subsets in atopic and nonatopic bronchial
      asthma.
AB  - BACKGROUND: Allergen-stimulated IL-5 production by CD4+ T cells is the key issue
      in atopic asthma. On the other hand, virus-specific CD8+ T cells produce IL-5 and
      might play an important role in the pathogenesis of nonatopic asthma. OBJECTIVES:
      We sought to compare the IL-5-producing T-lymphocyte subsets in the peripheral
      blood of atopic and nonatopic asthmatic subjects, especially the contribution of
      IL-5-producing CD8(+) T cells in nonatopic asthma. METHODS: Heparinized blood
      samples were obtained from subjects with atopic asthma (n = 10), subjects with
      nonatopic asthma (n = 10), and healthy subjects (n = 10) and stimulated with
      ionomycin and phorbol myristate acetate in the presence of brefeldin A. Two-color
      flow cytometric analysis with mAbs to cell-surface antigens and intracellular IL
      5 was used to detect the IL-5-producing T-cell subsets. RESULTS: A higher
      percentage of IL-5-producing CD3(+) T cells was detected in subjects with atopic
      and nonatopic asthma than that seen in the healthy subjects. The percentage of IL
      5-producing CD4(+) T cells was significantly higher in subjects with atopic
      asthma than in the healthy subjects. The percentage of IL-5-producing CD8(+) T
      cells was significantly higher in subjects with nonatopic asthma than in the
      healthy subjects. The percentage of IL-5-producing CD8(+) T cells was higher in
      subjects with nonatopic asthma than in those with atopic asthma, but the
      difference was not statistically significant. CONCLUSIONS: CD4(+) T cells are the
      major source of IL-5 among CD3(+) lymphocytes in subjects with atopic asthma. On
      the other hand, increased IL-5 production by CD8(+) T cells, as well as by CD4(+)
      T cells, is a characteristic feature of nonatopic asthma.

PMID- 11842301
TI  - Expression of eosinophil target SNAREs as potential cognate receptors for vesicle
      associated membrane protein-2 in exocytosis.
AB  - BACKGROUND: Exocytosis of eosinophil granule-derived mediators is thought to be
      an important effector response contributing to allergic inflammation. Secretion
      from many cell types has been shown to be dependent on the formation of a docking
      complex composed of soluble N-ethylmaleimide-sensitive factor attachment protein
      (SNAP) receptors (SNAREs) located on the vesicle (v-SNAREs) and the target
      membrane (t-SNAREs). The SNARE isoforms VAMP-2, SNAP-23, and syntaxin-4 have been
      described in secretory processes in myeloid cells. Previously, we have
      demonstrated that the v-SNARE VAMP-2 is a candidate v-SNARE involved in
      eosinophil exocytosis and is localized to a pool of RANTES-positive vesicles that
      translocate to the cell periphery after IFN-gamma-induced degranulation.
      OBJECTIVE: We sought to determine whether eosinophils express the t-SNARE
      isoforms SNAP-23 and syntaxin-4 as potential binding targets for VAMP-2 during
      exocytosis. METHODS: Human peripheral blood eosinophils (>97%) from atopic
      subjects were subjected to RT-PCR and sequence analysis by using specific primers
      for SNAP-23 and syntaxin-4. Protein expression and localization was determined by
      means of Western blot analysis of eosinophil subcellular fractions and confirmed
      with confocal laser scanning microscopy. RESULTS: Nucleotide sequences obtained
      from PCR products exhibited nearly identical (>95%) homology with reported
      sequences for human SNAP-23 and syntaxin-4. Both SNAP-23 and syntaxin-4 were
      present in plasma membranes, with some staining in endoplasmic reticulum and
      Golgi membranes. Negligible expression was detected in crystalloid and small
      secretory granules. CONCLUSIONS: The plasma membrane-associated t-SNAREs SNAP-23
      and syntaxin-4 are expressed in human eosinophils and are likely candidates for
      association with VAMP-2 during docking, which is followed by exocytosis. These
      findings support a role for SNARE molecules in eosinophil mediator release.

PMID- 11842302
TI  - Retinoic acid modulates IL-5 receptor expression and selectively inhibits
      eosinophil-basophil differentiation of hemopoietic progenitor cells.
AB  - BACKGROUND: IL-5 plays a central role in eosinophil and basophil differentiation,
      exerting its effects through the IL-5 receptor (IL-5Ralpha). Currently, little is
      known concerning regulation of IL-5Ralpha expression in the context of commitment
      of hemopoietic progenitor cells to the eosinophil and basophil lineages.
      OBJECTIVE: Because all-trans retinoic acid (ATRA) is known to modulate some
      aspects of hemopoietic differentiation, we examined the effects of ATRA on
      eosinophil-basophil differentiation and IL-5Ralpha expression. METHODS:
      Progenitor cells were obtained from bone marrow aspirates and cord blood samples.
      Enriched populations of CD34(+) cells were isolated by means of positive
      immunomagnetic selection with MACS beads. RESULTS: In semisolid methylcellulose
      cultures of normal human bone marrow, ATRA (10(-6) mol/L) selectively suppressed
      eosinophil-basophil colony-forming units but had no effect on granulocyte
      macrophage colony-forming units. Similarly, ATRA (10(-6) mol/L) inhibited
      eosinophil-basophil differentiation of cord blood CD34(+) cells in liquid
      culture, whereas neutrophil differentiation proceeded without impediment. Most
      importantly, these effects of ATRA (10(-8) to 10(-6) mol/L) on CD34(+) cells were
      associated with a dose-dependent inhibition of IL-5Ralpha but no change in GM-CSF
      receptor expression, as detected with flow cytometry. CONCLUSIONS: These findings
      indicate that retinoids can differentially regulate expression of IL-5Ralpha, but
      not GM-CSF receptor, and that these effects have functional consequences in vitro
      on eosinophil and basophil differentiation.

PMID- 11842303
TI  - Molecular, structural, and immunologic relationships between different families
      of recombinant calcium-binding pollen allergens.
AB  - BACKGROUND: Calcium-binding plant allergens can be grouped in different families
      according to the number of calcium-binding domains (EF hands). OBJECTIVE: We
      sought to identify pollens containing crossreactive calcium-binding allergens and
      to investigate structural and immunologic similarities of members belonging to
      different families of calcium-binding allergens. METHODS: By means of multiple
      sequence alignment and molecular modeling, we searched for structural
      similarities among pollen allergens with 2 (Phl p 7, timothy grass; Aln g 4,
      alder), 3 (Bet v 3, birch) and 4 EF hands (Jun o 4, prickly juniper). Purified
      recombinant Aln g 4 and Jun o 4 were used to determine the prevalence of IgE
      recognition in 210 patients sensitized to different pollens and to search, by
      means of ELISA competition, for the presence of cross-reactive epitopes in
      pollens from 16 unrelated plant species. IgE cross-reactivity among the allergen
      families was studied with purified rPhl p 7, rAln g 4, rBet v 3, and rJun o 4 and
      2 synthetic peptides comprising the N-terminal and C-terminal EF hands of Phl p 7
      by means of ELISA competition. RESULTS: Structural similarities were found by
      using molecular modeling among the allergens with 2, 3, and 4 EF hands. Pollens
      from 16 unrelated plants contained Aln g 4- and Jun o 4-related epitopes. Twenty
      two percent of the patients with multiple pollen sensitization reacted to at
      least one of the calcium-binding allergens. A hierarchy of IgE cross-reactivity
      (rPhl p7 > rAln g 4 > rJun o 4 > rBet v 3) could be established that identified
      rPhl p 7 as the EF-hand allergen containing most IgE epitopes in the population
      studied. CONCLUSION: The demonstration that members of different families of
      calcium-binding plant allergens share similarities suggests that it may be
      possible to use representative molecules for the diagnosis and therapy of
      allergies to EF-hand allergens.

PMID- 11842304
TI  - Scavenger receptor-specific allergen delivery elicits IFN-gamma-dominated
      immunity and directs established TH2-dominated responses to a nonallergic
      phenotype.
AB  - BACKGROUND: Immunotherapeutic approaches to allergy consist of reliably changing
      allergen-specific T(H)2 immunity associated with secretion of IL-4, IL-5, and IL
      13, along with IgE antibodies in atopic individuals to T(H)1 immunity. Our
      earlier data show that targeting of protein antigens to antigen-presenting cells
      (APCs), such as macrophages, by means of scavenger receptors (SRs) results in a
      pronounced T(H)1 immunity. Here we demonstrate a novel experimental approach for
      the conversion of T(H)2 immunity to T(H)1 immunity by using SR delivery of
      allergens. OBJECTIVES: We sought to show that targeting of allergens by means of
      SRs to APCs triggers T(H)1 immunity and that an established T(H)2 immunity to the
      Der p 1-immunodominant peptide 111-139 (p1, 111-139) can be modulated to a
      nonallergic T(H)1 phenotype. METHODS: Analysis of the T cell-derived cytokines IL
      4, IL-5, IL-13, and IFN-gamma in response to p1, 111-139 in C57BL/6 mice 7 to 42
      days after immunization, measurement of specific antibody responses, eosinophilic
      infiltrate, and skin hypersensitivity in response to allergen challenge
      constitute the parameters of in vivo immunity. RESULTS: We show that p1, 111-139,
      when delivered to APCs by means of SR, elicits a T(H)1-dominant immunity. If it
      is delivered to APCs either after chemical coupling to SR ligands or by means of
      mere coadsorption on alum in the presence of an SR ligand, the established T(H)2
      immunity can be modified to T(H)1 immunity. CONCLUSIONS: SR-mediated delivery of
      allergens has immunotherapeutic potential that may be usable in atopic
      individuals.

PMID- 11842306
TI  - T(H)1/T(H)2 immune response profiles differ between atopic children in eastern
      and western Germany.
AB  - BACKGROUND: Lower prevalence rates for childhood respiratory allergies have been
      reported in eastern Germany than in western Germany. OBJECTIVE: Because allergic
      phenotypes are thought to be associated with an unbalanced T(H)1/T(H)2 T cell
      effector response, a cross-sectional investigation was carried out as part of the
      German ISAAC Phase II study to determine whether T(H)1/T(H)2 capacity might have
      developed in different directions during the separation between the 2 parts of
      the country. METHODS: In a community-based random sample of 9- to 11-year-old (n
      = 6399) and 5- to 7-year-old (n = 6202) children in eastern and western Germany,
      the prevalence of atopy was assessed. Heparinized blood samples were collected
      from a subgroup of children stratified according to the number of older siblings.
      T(H)1 and T(H)2 cytokine productivity was determined after stimulation with
      phorbol ester plus ionomycin. RESULTS: Individuals who grew up in eastern Germany
      had a marked bias toward T(H)0 responsiveness (>60%), regardless of whether they
      were atopic. In contrast, the children of western Germany, particularly when they
      were atopic, showed T(H)2 polarization. CONCLUSIONS: This is the first
      epidemiologic survey to demonstrate regional differences in the T(H)1/T(H)2
      response pattern and their relation to atopic disease between regions.

PMID- 11842305
TI  - T cells and eosinophils cooperate in the induction of bronchial epithelial cell
      apoptosis in asthma.
AB  - BACKGROUND: Asthma is an inflammatory airway disease associated with an
      infiltration of T cells and eosinophils, increased levels of pro-inflammatory
      cytokines, and shedding of bronchial epithelial cells (ECs). OBJECTIVE: Shedding
      of bronchial ECs is characterized by loss of the normal bronchial
      pseudostratified epithelium and the maintenance of a few basal cells on a
      thickened basement membrane. The aim of this study was to investigate whether,
      and by which mechanism, T cells and eosinophils can cause damage to airway ECs.
      METHODS: Bronchial ECs, cultured and exposed to cytokines, eosinophil cationic
      protein, activated T cells, and eosinophils were studied for the expression of
      apoptosis receptors (flow cytometry, immunoblotting, and RNA expression) and for
      the susceptibility for undergoing apoptosis. In addition, bronchial biopsy
      specimens from patients with asthma were evaluated for EC apoptosis. RESULTS: We
      demonstrate herein that the respiratory epithelium is an essential target of the
      inflammatory attack by T cells and eosinophils. Bronchial ECs underwent cytokine
      induced cell death with DNA fragmentation and morphologic characteristics of
      apoptosis mediated by activated T cells and eosinophils. T cell- and eosinophil
      induced EC apoptosis was blocked by inhibition of IFN-alpha and TNF-alpha; the
      Fas ligand-Fas pathway appears to be less important. Recombinant eosinophil
      cationic protein induced mainly necrosis of ECs. Furthermore, we demonstrated in
      situ apoptotic features of ECs in bronchial biopsy specimens of asthmatic
      patients. CONCLUSION: T cell- and eosinophil-induced apoptosis represents a key
      pathogenic event leading to EC shedding in asthma.

PMID- 11842307
TI  - Aromatic components of food as novel eliciting factors of pseudoallergic
      reactions in chronic urticaria.
AB  - BACKGROUND: Pseudoallergic reactions (PARs) against both additives and natural
      foods have been reported to elicit chronic urticaria, but in natural food the
      responsible ingredients are largely unknown. OBJECTIVE: The study was aimed at
      identifying novel pseudoallergens in food and focused on evaluating tomatoes,
      white wine, and herbs as frequently reported food items eliciting wheal responses
      in urticaria. METHODS: In 33 patients with chronic urticaria and PARs to food
      (proved by means of elimination diet and subsequent re-exposure with provocation
      meals), oral provocation tests were performed with field-grown tomatoes,
      organically grown white wine (whole food, steam distillates, and residues), oily
      extracts from herbs, and food additives. In addition, skin biopsy specimens from
      patients were studied for in vitro mast-cell histamine release with tomato
      distillate alone or on subsequent stimulation with anti-IgE, substance P, and
      C5a. RESULTS: Seventy-six percent of patients reacted to whole tomato (steam
      distillate, 45%; residue, 15%), 50% to food additives, 47% to herbs, and 44% to
      whole wine (extract, 27%; residue, 0%). Histamine, protein, and high levels of
      salicylate were only found in residues. The tomato distillate was further
      analyzed by means of mass spectroscopy, identifying low molecular-weight
      aldehydes, ketones, and alcohol as major ingredients. In vitro histamine release
      was not caused by tomato extract itself but was enhanced by means of subsequent
      stimulation with substance P and C5a but not by anti-IgE. CONCLUSION: Aromatic
      volatile ingredients in food are novel agents eliciting PARs in chronic
      urticaria. Histamine, salicylate, and a direct mast-cell histamine release are
      not involved in this reactivity to naturally occurring pseudoallergens.

PMID- 11842308
TI  - Evidence for aberrant regulation of the p21Ras pathway in PBMCs of patients with
      chronic idiopathic urticaria.
AB  - BACKGROUND: Recent data suggest that a subpopulation of patients with chronic
      urticaria has an autoimmune disorder. Aberrant expression and regulation of the
      p21Ras pathway has been reported in lymphoid cells in a variety of systemic
      autoimmune diseases but not in chronic idiopathic urticaria (CIU). OBJECTIVES:
      The aim of this study was to examine the expression, regulation, and function of
      the p21Ras pathway in patients with CIU. METHODS: Twenty-four patients with CIU
      and 14 control subjects were enrolled. All patients and 9 control subjects were
      intradermally injected with autologous serum. PBMCs were isolated, and the p21Ras
      and its regulatory proteins were studied. RESULTS: We found increased expression
      of the p21ras proto-oncogene in patients with CIU. This was associated with a low
      expression of the p21Ras stimulatory element human son of sevenless (hSOS1) but
      normally expressed p21Ras inhibitory element p120GTPase-activating protein. The
      basal nonstimulated membrane/cytoplasmic ratio of hSOS1, which indicates the
      p21Ras pathway activity, was higher in patients compared with that seen in
      control subjects. Moreover, after stimulation, both patients and control subjects
      decreased their hSOS1 membrane/cytoplasmic ratio. The magnitude of this decrease
      was much higher in patients than in control subjects: 14- and approximately 2
      fold, respectively. The basal and stimulated activities of the p21Ras downstream
      key regulatory enzyme mitogen-activated protein kinase were comparable in
      patients and control subjects, as was their in vitro mitogen-stimulated
      lymphocyte proliferation. CONCLUSION: Our data demonstrate for the first time an
      aberrant signaling through the p21Ras pathway in lymphocytes of patients with
      CIU. This finding further supports the autoimmune basis of this disease.

PMID- 11842310
TI  - The use of skin prick tests and patch tests to identify causative foods in
      eosinophilic esophagitis.
AB  - BACKGROUND: Eosinophilic esophagitis is a disease entity in which patients have
      (1) elevated eosinophils on esophageal biopsy and (2) symptoms of
      gastroesophageal reflux. The symptoms do not improve on aggressive acid blockade
      but do improve on elimination diet or corticosteroid treatment, which tentatively
      links food allergies to this disorder. OBJECTIVE: The purpose of this study was
      to identify potential food antigens in eosinophilic esophagitis. METHODS:
      Patients with eosinophilic esophagitis were identified by biopsy. Potential food
      antigens were identified prospectively by skin prick testing and patch testing,
      which were performed through use of standard methods. Atopic tendencies,
      demographics, and potential food allergies were identified. Repeat esophageal
      biopsies were reviewed when possible. RESULTS: A total of 26 patients (22 male, 4
      female) with a biopsied-confirmed diagnosis of eosinophilic esophagitis underwent
      both skin prick testing and patch testing to identify potential causative foods.
      Milk and egg were the most common positive foods with skin prick testing. Wheat
      was the most common positive food with patch testing. The patients were advised
      to avoid positive foods as identified by skin prick testing and patch testing. In
      all, 18 patients had resolution of their symptoms, 6 patients had partial
      improvement, and 2 were lost to follow-up. Overall, after intervention,
      esophageal eosinophil counts improved from 55.8 to 8.4 eosinophils per high-power
      field. The foods most commonly identified by patients as causing symptoms were
      milk and egg. CONCLUSION: The combination of skin prick testing and patch testing
      can identify potential causative foods that might contribute to the pathogenesis
      of eosinophilic esophagitis.

PMID- 11842309
TI  - Cell-surface expression of CD25, CD26, and CD30 by allergen-specific T cells is
      intrinsically different in cow's milk allergy.
AB  - BACKGROUND: The release of T(H)2 cytokines by food-specific T cells is thought to
      be important in the etiology of food allergy. It has been suggested that the
      activation state of food-specific T cells also plays a significant role, but this
      has not yet been studied at the single-cell level. OBJECTIVE: Differences in the
      expression of cell-surface markers by cow's milk protein (CMP)-specific T cells
      between infants with and without cow's milk allergy (CMA) were evaluated at the
      clonal level. In addition, expression after the spontaneous development of
      tolerance of cow's milk in infants with CMA was analyzed. METHODS: We established
      CMP-specific T-cell clones (TCCs) from blood of infants with CMA and atopic
      dermatitis, from atopic controls with atopic dermatitis but without CMA, and from
      nonatopic controls. In addition, we established TCCs from infants with CMA after
      they had spontaneously developed tolerance to cow's milk. Expression levels of
      CD25, CD26, and CD30 by each TCC were analyzed by use of flow cytometry. RESULTS:
      Cow's milk protein-specific T cells from infants with CMA expressed much higher
      levels of CD25 and CD30 than CMP-specific T cells from infants without CMA.
      Expression of CD26 was much lower than in normal controls. After development of
      tolerance for cow's milk, expression of CD25 and CD30 was decreased, whereas the
      expression of CD26 was increased to normal levels. CONCLUSION: Antigen-specific T
      cells from patients with food allergy display an increased expression of cell
      surface markers of activation compared with cells of patients without food
      allergy. This suggests an intrinsically stronger food-specific T-cell response in
      food-allergic patients, and points to the key role of food-specific T cells in
      the pathogenesis of food allergy.

PMID- 11842311
TI  - A defect in corticosteroid-induced IL-10 production in T lymphocytes from
      corticosteroid-resistant asthmatic patients.

PMID- 11842312
TI  - Urticaria and angioedema induced by COX-2 inhibitors.

PMID- 11842313
TI  - Fresh-frozen plasma as a treatment for life-threatening ACE-inhibitor angioedema.

PMID- 11842314
TI  - A case of allergy to airborne, heat-labile shrimp allergens.

PMID- 11842315
TI  - Chronic sinusitis with rofecoxib.

PMID- 11842317
TI  - Therapeutic significance of distal airway inflammation in asthma.
AB  - Inflammation in asthma is not merely confined to the large central airways but
      also extends to the small peripheral airways. Distal lung inflammation can be
      observed even in patients with asthma with mild disease and normal spirometric
      readings. Subjects with asymptomatic asthma can exhibit significant increases in
      peripheral airway resistance, likely the result of distal lung inflammation. As
      determined from measurements of eosinophilic and other cellular infiltrates, the
      inflammatory response in the distal lung can exceed that in the large airways.
      Nocturnal asthma, a natural model of cyclic asthma worsening, is associated with
      an increase in nighttime distal lung inflammation, as evidenced by the
      accumulation of alveolar tissue eosinophils. Distal lung disease appears to
      increase the risk of recurrent asthma exacerbation, whereas disease-related
      anatomic changes in the small airways of the distal lung are prominent in fatal
      asthma. The clinical significance of distal lung disease makes this region an
      important therapeutic target. Chlorofluorocarbon (CFC)-based preparations of
      inhaled corticosteroids used to treat airway inflammation produce aerosols of
      relatively large particle size (approximately 4 microm); such aerosols have poor
      access to the distal lung. New formulations of inhaled corticosteroids that use
      hydrofluoroalkane (HFA) propellants can have smaller particle sizes
      (approximately 1 microm). Extrafine HFA aerosols have better access to the distal
      lung, with less oropharyngeal deposition. Imaging studies suggest that anti
      inflammatory medication delivered as an extrafine aerosol produces beneficial
      changes in distal lung function. In one study, an HFA formulation of an inhaled
      corticosteroid reduced air trapping to a greater degree than a CFC formulation of
      the same corticosteroid. By extending the delivery of anti-inflammatory
      medication to the distal lung, the new HFA-based corticosteroids have the
      potential to treat asthma more effectively and at reduced steroid doses.

PMID- 11842319
TI  - Microbial contamination of medicinal plants--a review.
AB  - Medicinal plants may be associated with a broad variety of microbial
      contaminants, which are represented by bacteria, fungi and viruses. Inevitably,
      this microbiological background depends on several environmental factors and
      exerts an important impact on the overall quality of herbal products and
      preparations. Risk assessment of the microbial load of medicinal plants has
      therefore become an important subject in the establishment of modern Hazard
      Analysis and Critical Control Point (HACCP) schemes. This study intends to
      contribute to this knowledge by giving a survey of published data regarding the
      microbial contamination of herbal plants, by dealing with methodological aspects
      and by considering the influence of different commonly used pharmaceutical
      preparation techniques on the microbiological status of the products. Finally,
      quality standards are discussed, which could be considered for guidelines and/or
      possible inclusion in the Ph.Eur. 2000.

PMID- 11842320
TI  - Antioxidant effects of 1,5-anhydro-D-fructose, a new natural sugar, in vitro.
AB  - The antioxidant effects of 1,5-anhydro-D-fructose (1,5-AF), a unique
      anhydrohexulose, were studied in 1,1-diphenyl-2-picrylhydrazyl (DPPH) solution,
      in human cells along with lipid peroxidation of low-density lipoprotein (LDL). We
      have confirmed that 1,5-AF scavenges DPPH radicals directly in solution and
      inhibits the formation of hydrogen peroxide and superoxide anion, typical
      reactive oxygen species (ROS), induced by phorbol myristate acetate (PMA) in a
      dose-dependent manner in THP-1 cells. We also observed the dose-dependent
      antioxidant effects of 1,5-AF on copper-mediated LDL oxidation. These findings
      suggest that 1,5-AF might play a role in reducing the risk of atherosclerosis and
      may help prevent coronary heart disease.

PMID- 11842321
TI  - Antiviral activity of simalikalactone D, a quassinoid from Quassia africana.
AB  - After removing lipophilic material, the ground root bark of Quassia africana
      Baill. (Simaroubaceae) was extracted with ethanol 95 %. Partitioning between
      chloroform, ethyl acetate and water yielded three crude extracts. Pronounced
      activities were shown by the chloroform and ethyl acetate crude extracts against
      Herpes simplex, Semliki forest, Coxsackie and Vesicular stomatitis viruses. By
      repeated column chromatography and preparative thin layer chromatography on
      silica gel, two quassinoids, i. e., quassin and simalikalactone D were isolated.
      Structures of the pure compounds were established primarily using NMR
      spectroscopy. Mass spectral information confirmed the assigned structures.
      Simalikalactone D was responsible, at least in part, for the high antiviral
      activity observed for the chloroform crude extract. Quassin showed no activity.
      For quassinoids the ester group at C-15 and the epoxymethano bridge between C-8
      and C-13 appeared to be important structural features in order to exhibit a
      pronounced antiviral activity.

PMID- 11842322
TI  - Antiplatelet and anti-inflammatory constituents and new oxygenated xanthones from
      Hypericum geminiflorum.
AB  - Two new pentaoxygenated xanthones, 2,3-dihydroxy-1,6,7-trimethoxyxanthone (1) and
      3,6-dihydroxy-1,5,7-trimethoxyxanthone (2) were isolated from the leaf of
      Hypericum geminiflorum. The antiplatelet activities of the constituents, 2,6
      dimethoxy-p-benzoquinone (3), gemichalcone A (4), gemichalcone B (5), and
      cycloartocarpin (6), of this plant, were assessed in vitro by determining their
      inhibitory effects on the aggregation of washed rabbit platelets induced by
      various inducers. The anti-inflammatory effects of 4 and 5 were assessed in vitro
      by determining their inhibitory effects on the chemical mediators released from
      mast cells and neutrophils. Of the compounds tested, 4 exhibited the most potent
      inhibition of platelet aggregation induced by arachidonic acid (AA) and 4 and 5
      strongly inhibited the release of beta-glucuronidase and lysozyme in formyl-Met
      Leu-Phe (fMLP)-stimulated rat neutrophils.

PMID- 11842323
TI  - Mechanisms of relaxant action of 3-O-methylquercetin in isolated guinea pig
      trachea.
AB  - We investigated the mechanisms of action of 3-O-methylquercetin (3-MQ), isolated
      from Rhamnus nakaharai (Hayata) Hayata (Rhamnaceae) which is used as a folk
      medicine for treating constipation, inflammation, tumors and asthma in Taiwan.
      The tension changes of tracheal segments were isometrically recorded on a
      polygraph. 3-MQ concentration-dependently relaxed histamine (30 microM)-,
      carbachol (0.2 microM)- and KCl (30 mM)-induced precontractions, and inhibited
      cumulative histamine-, and carbachol-induced contractions in a non-competitive
      manner. 3-MQ also concentration-dependently and non-competitively inhibited
      cumulative Ca(2+)-induced contractions in depolarized (K(+), 60 mM) guinea-pig
      trachealis. The nifedipine (10 microM)-remaining tension of histamine (30 microM)
      induced precontraction was further relaxed by 3-MQ, suggesting that no matter
      whether VDCCs were blocked or not, 3-MQ may have other mechanisms of relaxant
      action. The relaxant effect of 3-MQ was unaffected by the removal of epithelium
      or by the presence of propranolol (1 microM), 2',5'-dideoxyadenosine (10 microM),
      methylene blue (25 microM), glibenclamide (10 microM), N(omega)-nitro-L-arginine
      (20 microM), or alpha-chymotrypsin (1 U/ml). However, 3-MQ (7.5 - 15 microM) and
      IBMX (3 - 6 microM), a positive control, produced parallel and leftward shifts of
      the concentration-response curve of forskoline (0.01 - 3 microM) or nitroprusside
      (0.01 - 30 microM). 3-MQ or IBMX at various concentrations (10 - 300 microM)
      concentration-dependently and significantly inhibited cAMP- and cGMP-PDE
      activities of the trachealis. The IC50 values of 3-MQ were estimated to be 13.8
      and 14.3 microM, respectively. The inhibitory effects of 3-MQ on both enzyme
      activities were not significantly different from those of IBMX, a non-selective
      PDE inhibitor. The above results reveal that the mechanisms of relaxant action of
      3-MQ may be due to its inhibitory effects on both PDE activities and its
      subsequent reducing effect on [Ca(2+)]i of the trachealis.3-MQ:3-O
      methylquercetinIBMX:3-isobutyl-1-methylxanthineVDCCs:voltage dependent calcium
      channelscAMP:adenosine 3',5'-cyclic monophosphatecGMP:guanosine 3',5'-cyclic
      monophosphatePDE:phosphodiesteraseWe investigated the mechanisms of action of 3-O
      methylquercetin (3-MQ), isolated from Rhamnus nakaharai (Hayata) Hayata
      (Rhamnaceae) which is used as a folk medicine for treating constipation,
      inflammation, tumors and asthma in Taiwan. The tension changes of tracheal
      segments were isometrically recorded on a polygraph. 3-MQ concentration
      dependently relaxed histamine (30 microM)-, carbachol (0.2 microM)- and KCl (30
      mM)-induced precontractions, and inhibited cumulative histamine-, and carbachol
      induced contractions in a non-competitive manner. 3-MQ also concentration
      dependently and non-competitively inhibited cumulative Ca(2+)-induced
      contractions in depolarized (K(+), 60 mM) guinea-pig trachealis. The nifedipine
      (10 microM)-remaining tension of histamine (30 microM)-induced precontraction was
      further relaxed by 3-MQ, suggesting that no matter whether VDCCs were blocked or
      not, 3-MQ may have other mechanisms of relaxant action. The relaxant effect of 3
      MQ was unaffected by the removal of epithelium or by the presence of propranolol
      (1 microM), 2',5'-dideoxyadenosine (10 microM), methylene blue (25 microM),
      glibenclamide (10 microM), N(omega)-nitro-L-arginine (20 microM), or alpha
      chymotrypsin (1 U/ml). However, 3-MQ (7.5 - 15 microM) and IBMX (3 - 6 microM), a
      positive control, produced parallel and leftward shifts of the concentration
      response curve of forskoline (0.01 - 3 microM) or nitroprusside (0.01 - 30
      microM). 3-MQ or IBMX at various concentrations (10 - 300 microM) concentration
      dependently and significantly inhibited cAMP- and cGMP-PDE activities of the
      trachealis. The IC50 values of 3-MQ were estimated to be 13.8 and 14.3 microM,
      respectively. The inhibitory effects of 3-MQ on both enzyme activities were not
      significantly different from those of IBMX, a non-selective PDE inhibitor. The
      above results reveal that the mechanisms of relaxant action of 3-MQ may be due to
      its inhibitory effects on both PDE activities and its subsequent reducing effect
      on [Ca(2+)]i of the trachealis.3-MQ:3-O-methylquercetinIBMX:3-isobutyl-1
      methylxanthineVDCCs:voltage dependent calcium channelscAMP:adenosine 3',5'-cyclic
      monophosphatecGMP:guanosine 3',5'-cyclic monophosphatePDE:phosphodiesterase

PMID- 11842324
TI  - Taxanes in Taxus baccata pollen: cardiotoxicity and/or allergenicity?
AB  - Diterpenic alkaloids belonging to taxine (yield: 0.18 % dry weight) and taxoids
      (paclitaxel, baccatine III and 10-deacetylbaccatine III, cumulated yield: 0.004 %
      dry weight) were isolated from Taxus baccata L. pollen. Moreover, taxoids
      conjugated to macromolecules were also detected by ELISA. According to these data
      and to semi-quantitative measurements of pollen production, a hundred-year-old
      yew during its flowering time releases several grams of taxanes contained in 16
      to 20 kg of pollen. Toxicity assays on mice indicated that any risk of acute
      toxicity resulting from Taxus pollen inhalation and subsequent taxine absorption
      is unlikely. On the other hand, anti-paclitaxel IgG were above all detected in
      sera of subjects displaying hypersensitivity reactions during the pollination
      periods of Taxus sp. and Betula sp. This natural anti-paclitaxel IgG acquisition
      by individuals living in the distribution areas of these trees could be at the
      origin of atopic manifestations. We also postulate that such a natural
      sensitization could have a marked influence on the tolerance to anticancer
      taxoids.

PMID- 11842325
TI  - New and antifungal xanthones from Calophyllum caledonicum.
AB  - Two new xanthones, namely caledonixanthones E (1) and F (2), were isolated from
      the stem bark of Calophyllum caledonicum (Guttiferae). The structural elucidation
      of these compounds was mainly established on the basis of 1D, 2D NMR and HRMS
      spectroscopic analysis. Among the isolated compounds, eight other known xanthones
      were also identified in the course of this phytochemical study. In addition to
      this report, a preliminary evaluation of the antifungal properties of these
      polyphenolic compounds against Aspergillus fumigatus and Candida albicans is
      presented.

PMID- 11842326
TI  - Evaluation of antimycobacterial, antiplasmodial and cytotoxic activities of
      preussomerins isolated from the lichenicolous fungus Microsphaeropsis sp. BCC
      3050.
AB  - A new preussomerin isomer, 3'-O-demethylpreussomerin I, five known preussomerins
      E - I, and two known deoxypreussomerins, deoxypreussomerin A and bipendensin
      (palmarumycin C11), were isolated from a lichenicolous fungus Microsphaeropsis
      sp. BCC 3050. These structures were elucidated by spectroscopic methods,
      especially 1D- and 2D-NMR. The preussomerins were evaluated for their
      antimycobacterial and antiplasmodial activities as well as cytotoxicity against
      KB, BC-1 and vero cell lines.

PMID- 11842328
TI  - Eremophilane sesquiterpenes from Cacalia ainsliaeflora.
AB  - Chemical investigation of Cacalia ainsliaeflora afforded four new eremophilane
      sesquiterpenes (1 - 3, 5) and a known sesquiterpene (4), which were identified as
      3 beta-angeloyloxy-8 alpha-hydroxy-6 beta-methoxyeremophil-7(11),9(10)-dien-8,12
      olide (1), 3 beta-angeloyloxy-6 beta,8 alpha-dihydroxyeremophil-7(11),9(10)-dien
      8,12-olide (2), 3 beta-angeloyloxy-8 alpha-hydroxy-6 beta-ethoxyeremophil
      7(11),9(10)-dien-8,12-olide (3), 3 beta-angeloyloxy-8-oxo-eremphila-6,9-dien-12
      oic acid (4), and 3,8-oxo-eremophila-6,9-dien-12-oic acid (5) respectively. These
      compounds were assayed against Escherichia coli, Staphylococcus aureus and
      Bacillus subtilis, and compounds 1, 2, 4 and 5 showed weak antibacterial
      activity. The structures of the compounds were established by 1D and 2D NMR
      experiments.

PMID- 11842327
TI  - Natural products inhibiting Candida albicans secreted aspartic proteases from
      Tovomita krukovii.
AB  - Assay-guided fractionation of the ethanol extract of Tovomita krukovii resulted
      in the identification of four new xanthones (1 - 4) and ten known compounds (5 -
      14). The structures of compounds 1 - 14 were determined by spectral data to be
      3,5-dihydroxy-4-methoxyxanthone (1), 1,3,5,7-tetrahydroxy-8-isoprenylxanthone
      (2), 1,3,5-trihydroxy-8-isoprenylxanthone (3), 1,5,7-trihydroxy-8
      isoprenylxanthone (4), 1,3,7-trihydroxy-2-isoprenylxanthone (5), 1,5
      dihydroxyxanthone (6), 1,6-dihydroxy-5-methoxyxanthone (7), 1,3,5
      trihydroxyxanthone (8), 1,3,6-trihydroxy-5-methoxyxanthone (9), 1,6-dihydroxy-3,5
      dimethoxyxanthone (10), 1,3,7-trihydroxyxanthone (11), 3-geranyl-2,4,6
      trihydroxybenzophenone (12), betulinic acid (13), and 3,4-dihydroxybenzoic acid
      (14). Compounds 2, 3, 12 and 13 showed inhibitory effects against Candida
      albicans secreted aspartic proteases (SAP) with IC50 values of 15 microg/ml, 25
      microg/ml, 40 microg/ml, and 6.5 microg/ml, respectively, while the other
      compounds were inactive. In addition, compound 12 showed activity against C.
      albicans, C. neoformans, S. aureus and methicillin resistant S. aureus (MRS).

PMID- 11842329
TI  - DNA fingerprinting of Cannabis sativa using inter-simple sequence repeat (ISSR)
      amplification.
AB  - Chemical analysis of cannabinoid, and Inter-Simple Sequence Repeat (ISSR)
      fingerprinting of DNA were used to identify different samples of Cannabis sativa
      L. for forensic purposes. Three samples were classified into two types,
      tetrahydrocannabinol (THC) and cannabidiol (CBD) chemo-types, by high performance
      liquid chromatography (HPLC). The two samples of the CBD type were not
      distinguished by their HPLC patterns. ISSR fingerprinting identified polymorphic
      DNA patterns between these samples. ISSR fingerprinting clearly differentiated
      between cannabis samples that could not be achieved by HPLC analysis.

PMID- 11842330
TI  - Radical scavengers from the entomogenous deuteromycete Beauveria amorpha.
AB  - The culture medium of Beauveria amorpha Hohn. exhibited strong radical scavenging
      properties. Activity-directed fractionation assisted by a radical scavenging
      assay on TLC afforded two active compounds which were identified as 6-methyl-2,4
      dihydroxyphenyl 4-O-methyl-beta-D-glucopyranoside (1) and (-)-terredionol (2).
      Compound 1 displays radical scavenging and lipid peroxidation inhibitory activity
      comparable to those of TroloxC, ascorbic acid or quercetin.

PMID- 11842331
TI  - Methyl psilalate: a new antimicrobial metabolite from Psila boliviensis.
AB  - Psila boliviensis (Wedd.) Cabr. yielded a new phenylpropanoid, named methyl
      psilalate. The structure was established by means of standard spectroscopic
      techniques. The microbiological evaluation of the compound revealed antibacterial
      activity against Gram-positive and Gram-negative bacteria.

PMID- 11842332
TI  - Antiplasmodial and cytotoxic activity of galipinine and other
      tetrahydroquinolines from Galipea officinalis.
AB  - The antimalarial and toxicological properties of four tetrahydroquinoline
      alkaloids from Galipea officinalis trunk bark were studied. Crude extracts and
      pure alkaloids were tested for in vitro antimalarial activity on Plasmodium
      falciparum. The IC50 were evaluated after 24 and 72 h contact between compounds
      and the parasite culture, and ranged from 1.8 to 40 microg/ml for the chloroquine
      sensitive strain (CQS) and from 0.09 to 38 microg/ml for the chloroquine
      resistant strains (CQR). Galipinine yielded the best antimalarial effect (IC50:
      0.09 - 0.9 microg/ml on CQR strain) and this compound interacted particularly
      between the 32(nd) and the 40(th) hour of the P. falciparum erythrocytic cycle.
      The cytotoxicity of the extracts and pure tetrahydroquinoline alkaloids was
      assessed on the HeLa cell line and showed IC50 values ranging from 5.8 to above
      50 microg/ml.

PMID- 11842333
TI  - Saponins-mediated potentiation of cisplatin accumulation and cytotoxicity in
      human colon cancer cells.
AB  - The triterpene saponins jenisseensosides A, B, C, D were found to increase the
      accumulation and cytotoxicity of the anticancer agent cisplatin in human colon
      tumor cells. These compounds are glycosides of quillaic acid whose fucose residue
      was acylated by a trans- or cis-p methoxycinnamic acid. In contrast, other
      saponins derivatives without this acyl moiety were not found to potentiate the
      accumulation and cytotoxicity of cisplatin. These results suggested the
      importance of the acyl moiety for activity.

PMID- 11842334
TI  - Iridoids with anti-inflammatory activity from Vitex peduncularis.
AB  - A new iridoid, pedunculariside, together with the known iridoid agnuside were
      isolated from the butanol extract of Vitex peduncularis stem bark. Both
      pedunculariside and agnuside showed preferential inhibition of COX-2, with IC50
      values of 0.15 +/- 0.21 mg/ml and 0.026 +/- 0.015 mg/ml respectively, while
      having only small inhibitory effects on COX-1. Both compounds did not exhibit
      cytotoxicity against vero cells.

PMID- 11842335
TI  - Chemical properties and biological activity of a polysaccharide from Melocactus
      depressus.
AB  - An arabinogalactan with mean Mr of 6.85 x 10(4), was isolated from the pulps of
      Melocactus depressus Hook by fractionation on Sephacryl S-300 HR. Chemical and
      spectroscopic studies indicated that it has a branched arabinogalactan type
      structure composed of beta-(1-->4) linked D-galactopyranose residues with beta-(1
      ->3) and beta-(1-->6) branching points. Its structural features include also
      alpha-(1-->2), alpha-(1-->3) and alpha-(1-->5) linked L-arabinofuranose residues.
      The polysaccharide demonstrated a phagocytosis stimulating property.

PMID- 11842336
TI  - Biflavones of Ginkgo biloba stimulate lipolysis in 3T3-L1 adipocytes.
AB  - Ginkgo biloba L. biflavones were shown to increase cAMP phosphodiesterase
      activity and to stimulate skin microcirculation. The aim of this study was to
      investigate whether biflavones were able to stimulate lipolysis in adipocytes.
      Lipolysis was assayed in fully differentiated 3T3-L1 fat cells in the presence of
      biflavones at 0.005 - 100 microM. Cell viability was evaluated at 0.5 -100
      microM. Theophylline and caffeine were used as reference compounds. Lipolytic
      activity in untreated cells was 0.62 +/- 0.15 micromoles glycerol/mg DNA/h. All
      biflavones except sciadopitysin stimulated lipolysis in a concentration-dependent
      fashion. Maximal stimulation was observed at 0.1 - 0.5 microM. At higher
      concentrations the effect diminished progressively and was lost at 100 microM.
      Only a partial loss of cell viability was observed with biflavones at 10 - 100
      microM.

PMID- 11842338
TI  - A new coumarin from Murraya paniculata.
AB  - A new natural product, 2'-O-ethylmurrangatin (1) was isolated along with two
      previously known compounds murranganone (2) and paniculatin (3) from the leaves
      of Murraya paniculata. The structure of compound 1 was elucidated with the help
      of spectroscopic studies and by chemical reactions. Compounds 2 and 3 have been
      found to be cholinesterase inhibitors.

PMID- 11842337
TI  - The skin-lightening effects of artocarpin on UVB-induced pigmentation.
AB  - This study was conducted to evaluate the effects of the prenylated flavonol
      artocarpin from the heartwood of Artocarpus incisus on ultraviolet (UV)-induced
      hyperpigmentation of guinea pig skin. An efficient lightening effect was observed
      following topical application of artocarpin to UV-stimulated hyperpigmented
      dorsal skins of brownish guinea pigs.

PMID- 11842339
TI  - Monoamine oxidase inhibitory coumarin from Zanthoxylum schinifolium.
AB  - A methanol extract of Zanthoxylum schinifolium stems at a concentration of 250
      microg/ml showed potent inhibitory activity against monoamine oxidase (MAO) in a
      mouse brain. Activity-guided separation and purification of the extract yielded
      lacinartin (1) as an active coumarin compound. Lacinartin showed significant
      inhibitory effects on MAO in a dose-dependent manner. The IC(50) value on MAO
      activity was 9.2 microM. The MAO-A (IC(50) value, 5.7 microM) sensitivity to
      lacinartin was greater than that of MAO-B (IC(50) value, 28.6 microM). An enzyme
      kinetic study revealed that lacinartin inhibited MAO activity by a non
      competitive mode.

PMID- 11842340
TI  - Inhibition of HIV-1 reverse transcriptase and HIV-1 replication by Calophyllum
      coumarins and xanthones.
AB  - As part of our continuing study on the Calophyllum species, a number of
      coumarins, xanthones and chromene acids from different Calophyllum species of Sri
      Lanka were tested for inhibitory activity against the HIV-1 and its virally
      encoded reverse transcriptase (RT). These compounds were found to be inactive in
      both the HIV-1 RT and whole virus systems. In contrast, cordatolide A and B
      demonstrated IC(50) values of 19.3 and 11.7 microM, respectively, against HIV-1
      replication in a novel green fluorescent protein (GFP)-based reporter cell assay
      (HOG.R5).

PMID- 11842341
TI  - Phenolic compounds from Hypericum perforatum.
AB  - During a re-investigation of phenolic compounds from the dried crude drug
      material of St. John's wort (Hypericum perforatum L.) 22 phenolic compounds were
      detected by HPLC; 14 of them were quantified using the same system. Twelve
      phenolic compounds were isolated from the plant material and their structures
      identified mainly by spectroscopic methods, among them quercetin-3-O-(2"-O
      acetyl)-beta-D-galactoside as a new natural product. Cryptochlorogenic acid,
      protocatechuic acid, 3-O-[Z]-p-coumaroylquinic acid, isoorientin, cyanidin-3-O
      alpha-L-rhamnoside, and astilbin were obtained for the first time from this
      source; the earlier suspected neochlorogenic acid, 3-O-[E]-p-coumaroylquinic
      acid, mangiferin, miquelianin and guaijaverin were confirmed.

PMID- 11842342
TI  - New norsesquiterpenoids from Cucubalus baccifer.
AB  - The chemical investigation of Cucubalus baccifer L. afforded three new
      norsesquiterpenoids, cucubalol, cucubalactone and drummondol-11-O-beta-D
      glucopyranoside together with two known related compounds, drummondol and 5,7[E]
      megastigmadiene-3 beta,4 alpha,9 xi-triol. Their structures were established
      based on spectral and chemical evidence. No activity was observed in anti-cancer
      (CDC25), antibacterial (PEPT) and antifungal (YNG) assays.

PMID- 11842343
TI  - Genetic identification of cinnamon (Cinnamomum spp.) based on the trnL-trnF
      chloroplast DNA.
AB  - Genetic identification among cinnamon species was studied by analyzing nucleotide
      sequences of chloroplast DNA from four species (Cinnamomum cassia, C. zeylanicum,
      C. burmannii and C. sieboldii). The two regions studied were the intergenic
      spacer region between the trnL 3'exon and trnF exon (trnL -trnF IGS) and the trnL
      intron region. We found nucleotide variation at one site in the trnL-trnF IGS,
      and at three sites in the trnL intron. With the sequence data from analysis of
      these regions, the four Cinnamomum species used in this study were correctly
      identified. Furthermore, single-strand conformation polymorphism (SSCP) analysis
      of PCR products from the trnL-trnF IGS and the trnL intron resulted in different
      SSCP band patterns among C. cassia, C. zeylanicum and C. burmannii.

PMID- 11842344
TI  - [Care deficits in pneumological rehabilitation].

PMID- 11842345
TI  - [Therapy of bronchial carcinoma: interdisciplinary and with expertise].

PMID- 11842346
TI  - [Efficacy and safety of salmeterol (50 microgram) and fluticasone (250 microgram)
      in a single inhaler device (diskus) in patients with mild to moderate asthma].
AB  - BACKGROUND: Inhaled corticosteroids and long-acting beta-agonists are first-line
      agents for the treatment of patients with persisting bronchial asthma. Several
      lines of evidence have shown, that inhaled corticosteroids and long-acting beta
      agonist have multiple synergisms both in vivo and in vitro, leading to improved
      clinical asthma control. METHODS: A prospective, open, multi-centre study was
      performed to evaluate the efficacy and safety of a fixed combination of inhaled
      Fluticasone (250 microgram BID) and Salmeterol (50 microgram BID) in a single
      inhaler device (Diskus). 3345 patients (48 % male, mean age 52 years, range 17 -
      90 years) with mild to moderate asthma were treated over a period of 8 weeks.
      Lung function, quality of life and adverse events were evaluated as primary
      outcome variables. RESULTS: After 8 weeks of treatment, forced expiratory volume
      in one second (FEV1) improved from 2.37 +/- 0.86 l to 2.7 +/- 0.96 l (p < 0.001).
      Accordingly, morning peak expiratory flow (PEF) increased from 4.9 +/- 2.1 l/s to
      5.6 +/- 2.2 l/s (p < 0.001). Quality of life improved in 90 % of all patients,
      with an overall increase of 1.1. points. Frequent adverse events included
      symptoms of asthma (5.3 % of all adverse events) and infections (2.7 %). Typical
      side-effects of the study medication, e. g. oral candidiasis or tachycardia were
      observed in less than 2 % of all patients. CONCLUSIONS: These results confirm the
      efficacy and tolerability of a fixed combination of salmeterol and fluticasone in
      a single inhaler device (Diskus). Lung function and quality of life were
      significantly improved in mild to moderate asthmatics. A fixed combination of
      long-acting beta-agonists and inhaled corticosteroids is therefore considered as
      a valuable therapeutic option for the treatment of patients with asthma.

PMID- 11842347
TI  - [Spiroergometry in patients with severe chronic obstructive pulmonary disease
      confined to bed].
AB  - BACKGROUND: Exercise training is recommended for patients with severe chronic
      obstructive pulmonary disease (COPD) to improve the endurance capacity. While
      many patients confined to bed are not able to run exercise training, we
      investigated the influence of a bedside passive-ergometry on ventilation in
      patients with severe COPD. METHODS: In nine patients with severe COPD confined to
      bed (FEV1.0 0,94 +/- 0,18 l, IVC 2,3 +/- 0,8 l, Raw 0,91 +/- 0,13 kPa/l/s) we
      measured oxygen uptake O2, breathing frequency BF and minute ventilation E during
      rest, passive movement (30 revolutions per minute), additional active movement
      and maximal exercise. As a control group six healthy men were investigated during
      rest and passive movement. RESULTS: During maximal exercise in COPD patients O2
      peak reached 618 +/- 177 ml/min, BF 26 +/- 7,2/min and E max 24,1 +/- 5 l/min. In
      rest O2 was 311 +/- 56 ml/min (53 % O2 peak), BF 17,6 +/- 3,1/min and E 13,3 +/-
      2,7 ml/min (55 % E max), while during passive movement O2 was increased to 369 +/
      88 (62 % O2 peak), BF to 19 +/- 5,3 and E to 16,4 +/- 4,1 (68 % E max). In
      contrast O2 in control subjects dropped from 377,5 +/- 38 in rest to 336 +/- 27
      ml/min during passive action, BF from 14 +/- 2,1 to 12 +/- 2,4/min and E from
      11,1 +/- 1,3 to 9,1 +/- 1 ml/min. CONCLUSIONS: In patients with severe COPD
      oxygen uptake, breathing frequency and minute ventilation increased not only
      during active, but even during passive movement of a bedside ergometer. With this
      method an exercise training is possible even in COPD patients confined to bed.

PMID- 11842348
TI  - [Induction of direct antimicrobial activity through mammalian toll-like
      receptors].
AB  - Drosophila, the toll gene controls a powerful innate defense system against
      bacteria and fungi. Conserved through evolution, the mammalian innate immune
      system retains a family of homologous Toll-like receptors (TLRs) that are
      activated by microbial ligands to release cytokines that instruct the adaptive
      immune responses. Here we show that TLR2 activation leads to killing of
      intracellular Mycobacterium (M.) tuberculosis in both mouse and human
      macrophages. In mouse macrophages, bacterial lipoprotein activation of TLR2 leads
      to a nitric oxide-dependent killing of intracellular tubercle bacilli. In human
      monocytes and alveolar macrophages, bacterial lipoproteins similarly activated
      TLR2 to kill intracellular M. tuberculosis, however by an antimicrobial pathway
      that is nitric oxide independent. TLR2+CD14+CD68+ macrophages were detected in
      human lesions of tuberculous lymphadenitis within granulomas and surrounding foci
      of necrosis. These data provide evidence that mammalian TLRs have retained not
      only the structural features of Drosophila Toll that allow them to respond to
      microbial ligands, but also the ability directly to activate antimicrobial
      effector pathways at the site of infection.

PMID- 11842350
TI  - [Recommendations on the therapy of bronchial carcinoma].

PMID- 11842349
TI  - [Late pulmonary manifestation of ovarian and breast cancer--which contribution
      provide immunohistochemical techniques?].
AB  - The two case studies are describing 2 females with tumor-suspicious lung
      opacities including pleural effusions. Both patients have had a smoking history
      of more than 20 packyears and both underwent surgery for a breast respectively an
      ovarian cancer 10/15 years before. Conventional staining of the biopsies does not
      allow in most cases the differentiation between a primary lung carcinoma or the
      metastasis of an extrapulmonary tumor. Immunohistochemical techniques can give
      clues as to the origin of the primary tumor. The contribution of these methods in
      finding the correct diagnosis in the two presented cases is discussed. The
      cooperation between clinician and pathologist should be emphasized. The transfer
      of all important information is essential.

PMID- 11842351
TI  - [Difficult to manage asthma: clinical phenotypes and principles of therapy].

PMID- 11842352
TI  - Maintenance of bone mass and mechanical properties after short-term cessation of
      high impact exercise in rats.
AB  - Abstract. The effects of cessation of high-impact exercise on bone mass in female
      Wistar rats was assessed. Fifty 10-week old rats were randomly divided into five
      groups (n = 10): 4 weeks jump-exercise (4JEX), 4 weeks sedentary control (4S), 8
      weeks jump-exercise (8JEX), 4 weeks jump-exercise followed by 4 weeks sedentary
      (4JEX4S) and 8 weeks sedentary control (8S). The rats were jumped trained 40
      times/session, 5 days/week. After 4 weeks or 8 weeks the mass and breaking force
      in tibia and cross-sectional areas of the tibia were measured. The tibia in the
      4JEX and 8JEX groups had significantly greater fat-free dry weight and maximum
      loads at the fracture tests than those in the 4S and 8S groups. The tibia of 4JEX
      and 8JEX also had significantly larger cortical area without a significant change
      in the medullary area at the cross-sectional analysis. Bone mass acquired in
      4JEX4S group was retained after cessation of exercise. The results indicate that
      high-impact jump-exercise, which is osteotropic, leads to an increased cortical
      bone with enhanced periosteal bone formation, which is also, however, maintained
      after cessation of exercise. It is therefore suggested that high-impact jump
      exercise may provide greater safety margin against disuse-related or/and age
      related bone loss and skeletal fragility later in life.

PMID- 11842353
TI  - Evidence for exercise-induced bone formation in premature infants.
AB  - We assessed the effect of a four weeks exercise training intervention on bone
      turnover markers in premature infants. Twenty-four very low birth weight
      premature infants were matched for gestational age, birth weight, gender, as well
      as for corrected age and weight at initiation of the study. Then the subjects
      were randomly divided into an exercise (n = 12) and a control group (n = 12).
      Exercise consisted of passive range of motion exercise with gentle compression of
      both the upper and lower extremities lasting 5 - 10 minutes each day, 5 days per
      week for 4 weeks. This protocol has been shown to increase bone mineral density
      in premature infants. Bone formation was assessed by measurements of circulating
      bone specific alkaline phosphatase (BSAP) and the C-terminal procollagen peptide
      (PICP). Bone resorption was determined by serum measurements of C- terminal cross
      links telopeptide of type-I collagen (ICTP). Training led to a significant (P <
      0.05) increase in weight gain (767 +/- 49 versus 586 +/- 24 gr in trained and
      control premature infants, respectively); and to a significant increase in BSAP
      (37.2 +/- 14.6 versus 4.1 +/- 8.4 % in trained and control premature infants,
      respectively). PICP increased also following exercise (34.6 +/- 18.9 versus 5.4
      +/- 9.1 % in trained and control subjects, respectively), however, this increase
      was not statistically significant. Exercise led to a significant decrease in ICTP
      (-24.7 +/- 3.1 versus -5.5 +/- 5.4 % in trained and control subjects,
      respectively). A relatively brief exercise intervention was associated with a
      biochemical evidence of bone formation in very low birth weight premature
      infants.

PMID- 11842354
TI  - Effect of cold exposure on older humans.
AB  - Epidemiological studies have shown excess winter mortality particularly in older
      age groups. A question is how much these statistics are affected by age-related
      physiological changes in cold thermoregulation and how much due to other factors
      related to aging. In experimental studies concerning age and cold stress both
      whole-body and local exposures have been used mostly in resting subjects with
      minimal clothing. Older persons, particularly men over ca. 60 years, are less
      able to maintain core temperature during a given cold challenge compared to
      younger individuals. Older persons have a reduced cutaneous thermal sensitivity,
      and a reduced subjective thermal perception during cooling. Thus, older people
      may require a more intense stimulus to perform protective actions against cold
      stress. Older persons' skin vasoconstrictive response to cold is diminished
      compared to younger persons, which seems partly related to a reduced skin
      vasomotor sensitivity to sympathoneuronal stimuli. The cold-induced rise in
      metabolic rate is attenuated in older persons, but the mechanism is unknown. Both
      central and peripheral components seem to be involved in the age-related changes
      in regulatory effector functions. Enhanced aerobic fitness may not give added
      protection against core cooling during cold stress in the elderly, but seems to
      attenuate older subjects' heightened blood pressure response to cold. Bronchial
      responsiveness to face cooling may increase with age. Further studies are needed
      to examine the age-related changes in non-thermoregulatory responses to cold (e.
      g. hemodynamics, cardiac function, respiration, autonomic nervous function), and
      the modifying effects of acute exercise and physical training.

PMID- 11842355
TI  - Validity and reliability of critical speed, critical stroke rate, and anaerobic
      capacity in relation to front crawl swimming performances.
AB  - The purpose of this investigation was to determine whether the concepts of
      critical swimming speed, critical stroke rate and anaerobic swimming capacity
      could be used by coaches as a reliable index in order to monitor endurance
      performances in competitive swimmers. The results of this study conducted with
      well-trained swimmers showed that the 30-min test velocity (V30) is not different
      from the critical swimming speed determined from 200- and 400-m tests but is
      overestimated by 3.2 %. Furthermore, a regression analysis of the number of
      stroke cycles on time calculated for each swimmer showed a linear relationship
      (r(2) greater than 0.99 and p less than 0.01). The 30-min stroke rate test (SR30)
      was not different from the critical stroke rate determined from 200- and 400-m
      tests after a correction of minus 3.9 %. These data suggest that the slope of
      this regression line represents the critical stroke rate defined as the maximal
      stroke rate value, which can theoretically be maintained continuously without
      exhaustion. Coaches could easily use critical swimming speed combined with
      critical stroke rate in order not only to set aerobic training loads but also to
      control the swimming technique during training. Besides, anaerobic swimming
      capacity (ASC) values defined as the y-intercept of the regression line between
      distance and time were not correlated (p > 0.05) with the determined distance
      over which a significant drop in the maximal speed could be noticed on a 25-m
      test. Thus, ASC does not provide a reliable estimation of the anaerobic capacity.

PMID- 11842357
TI  - The locomotory index: a new proposal for evaluating walking impairments.
AB  - The energy cost of walking per unit of body mass and of distance (Cw) was
      determined before total hip (n = 17) or total knee (n = 16) arthroplasty and ten
      days, two, six or twelve months after surgery. The ratio of Cw observed on
      patients (at the self selected speed) relative to that observed in healthy
      subjects of the same age at the same speed was defined Locomotory Index (Index
      Locomotorius, IL). So, IL is a quantitative measure of the economy of walking;
      for both groups of patients IL amounted to about 1.40 before surgery; it
      increased significantly 10 days after the operation to 1.86 or to 1.58, for hip
      or knee patients, respectively. Two, six and twelve months after the operation IL
      had decreased significantly below presurgery values (1.29, 1.30 and 1.30) for
      knee replacement, whereas it was still larger, albeit not significantly so, after
      hip replacement (IL = 1.61; 1.56 and 1.50). It was also observed that the self
      selected speed increased and the traditional clinical scores (Harris for hip and
      B.O.A. for knee) improved, with decreasing IL. It is suggested that IL is a
      useful quantitative tool, in addition to the more traditional clinical scores,
      for evaluating ambulatory disability in patients.

PMID- 11842356
TI  - Coordination in front crawl in elite triathletes and elite swimmers.
AB  - The aim of this study was to compare the arm coordination in 19 elite triathletes
      and 15 elite swimmers at six different velocities between 80 % and 100 % of their
      maximal velocity (Vmax). The different phases of the stroke (A: entry; B: pull;
      C: push; D: recovery) were identified by video analysis. An index of coordination
      (IdC) was calculated. It was the time that separated the beginning of the
      propulsive phase of one arm from the end of the propulsive phase of the other
      arm. IdC allows to express the mode of arm coordination: catch-up, IdC < 0;
      opposition, IdC = 0; superposition, IdC > 0. Between 80 % and 98 % Vmax, elite
      triathletes showed similar increases in IdC than swimmers (from -8.8 % to 2.6 %
      vs from -8.6 % to 0.3 %) switching from a catch-up to a superposition
      coordination. Between 88 % and Vmax, triathletes increased the propulsive phase
      (B+C) less (p < 0.01) than swimmers (3.4 % vs 8.5 %) and increased the recovery
      phase (0.8 %) when swimmers reduced it (-1.6 %). Between V5 and Vmax, both
      triathletes and swimmers had a significant (p < 0.01) difference in IdC change (
      1.7 % vs 2.3 %). Moreover, triathletes reduced the propulsive phase when swimmers
      increased it (-0.6 % vs 3.2 %). The lower velocity of the triathletes was
      associated to a shorter stroke length when compared to the swimmers (1.70 m vs
      2.15 m at Vmax). The stroke rates were not statistically different (55.1 vs 51.2
      stroke x min(-1) at Vmax). Thus, monitoring IdC and stroke length is recommended
      for triathletes mainly at maximal velocity.

PMID- 11842358
TI  - The effects of strength training, cardiovascular training and their combination
      on flexibility of inactive older adults.
AB  - The purpose of this study was to investigate the effects of aerobic training,
      strength training and their combination on joint range of motion of inactive
      older individuals. Thirty-two inactive older men (65 - 78 yr) were assigned to
      one of four groups (n = 8 per group): control (C), strength training (ST),
      cardiovascular training (CT), and combination of strength and aerobic training
      (SA). Subjects in the S, A, and SA trained three times a week for 16 weeks. ST
      included 10 resistance exercises for the major muscle groups at an intensity of
      55 - 80% of 1-RM and CT included walking/jogging at 50 - 80 % of maximal heart
      rate. Body weight and height, physical activity level and maximal oxygen uptake
      (.VO(2)max) were measured before the training period. Isokinetic (60 and 180 deg
      x sec(-1)) and concentric strength (1-RM in bench and leg press) were assessed
      prior to and at the end of the training period. Hip flexion, extension,
      abduction, and adduction, shoulder extension, flexion, and adduction, knee
      flexion, elbow flexion and sit-and-reach score were determined before and at 8
      and 16 weeks of training. There were no differences between groups in .VO(2)max,
      body weight, and height (p < 0.05). ST and SA but not CT and C increased
      isokinetic and concentric strength at the end of the training period (p < 0.05).
      ST and SA increased significantly (p < 0.05) sit-and-reach performance, elbow
      flexion, knee flexion, shoulder flexion and extension and hip flexion and
      extension both at mid- and post-training. CT increased (p < 0.05) only hip
      flexion and extension at post training. Results indicate that resistance training
      may be able to increase range of motion of a number of joints of inactive older
      individuals possibly due to an improvement in muscle strength.

PMID- 11842359
TI  - Spontaneously chosen crank rate variations in submaximal arm exercise with
      inexperienced subjects. Effects on cardiorespiratory and efficiency parameters.
AB  - The aim of the present study was to compare the physiological responses during
      arm exercises when the crank rate was chosen spontaneously (TS) or set at +/- 20
      % (T-20, T+ 20) of the spontaneously chosen crank rate (SCCR). Eight physical
      education male students, aged 22 +/- 3.2 years, performed an upper body exercise
      in which intensities ranged from unload to 80 % of maximal power. No significant
      difference was observed in oxygen uptake, ventilation, gross and net efficiency
      values between TS and T+ 20 or T-20. Nevertheless, oxygen uptake and ventilation
      were significantly (p < 0.05) lower and gross and net efficiencies higher (p <
      0.05) during T-20 than T+ 20. No significant difference was noticed for heart
      rate, delta and work efficiency between TS, T-20 and T+ 20. The hypothesis that
      SCCR is the most economical one according to the efficiency parameters was not
      quite verified. However, crank rates lower than SCCR could be interesting because
      they increase gross efficiency compared to higher crank rates. Moreover, the
      selection of crank rates depends on power output. Indeed, SCCR increased
      significantly (p < 0.05) with power output. In the physical reconditioning of
      injured or handicapped subjects, the latter are very sensitive to the power
      output, and the crank rate could be another constraint.

PMID- 11842360
TI  - Aerobic demands of the dance simulation game.
AB  - The purpose of this study was to assess the intensity and energy cost of dance
      simulation in relation to the American College of Sports Medicine (ACSM)
      recommendations on the quantity and quality of exercise for developing and
      maintaining cardiorespiratory fitness, and to assess its safety. Forty subjects
      (21 males and 19 females, age 17.5 +/- 0.7 years) had their heart rate (HR) and
      oxygen consumption (.VO(2)) measured during maximal treadmill exercise and during
      a dance simulation game at a self-selected level of difficulty. They were
      monitored for injuries during and after the study. The results showed a mean HR
      of 137 beats x min(-1) (139 beats x min(-1) for males and 136 beats x min(-1) for
      females) and a mean .VO(2) of 24.6 ml x kg(-1) x min(-1) (25.3 ml x kg(-1) x min(
      1) for males and 23.8 ml x kg(-1) x min(-1) for females) during the dance
      simulation game test, with an estimated energy expenditure of 480 W (550 W for
      males and 410 W for females). The dance intensity only just meets the minimum
      ACSM guidelines, so dancer-players will need to play for extended periods to
      improve or maintain cardiorespiratory fitness or to lose weight. No injuries
      occurred during 201 hours of dance time.

PMID- 11842361
TI  - A comparison of the lactate Pro, Accusport, Analox GM7 and Kodak Ektachem lactate
      analysers in normal, hot and humid conditions.
AB  - This study aimed to compare the performance of a new portable lactate analyser
      against other standard laboratory methods in three conditions, normal (20 +/- 1.3
      degrees C; 40 +/- 5 % RH), hot (40 +/- 2.5 degrees C; 40 +/- 5 % RH), and humid
      (20 +/- 1.1 degrees C; 82 +/- 6 % RH) conditions. Seven healthy males, ([Mean +/-
      SE]: age, 26.3 +/- 1.3 yr; height, 177.7 +/- 1.6 cm; weight, 77.4 +/- 0.9 kg,
      .VO(2)max, 56.1 +/- 1.9 ml x kg x min(-1)) undertook a maximal cycle ergometry
      test to exhaustion in the three conditions. Blood was taken every 3 min at the
      end of each stage and was analysed using the Lactate Pro LT-1710, the Accusport,
      the Analox GM7 and the Kodak Ektachem systems. The MANOVA (Analyser Type x
      Condition x Workload) indicated no interaction effect (F(42,660), = 0.45, p >
      0.99, Power = 0.53). The data across all workloads indicated that the machines
      measured significantly differently to each other (F(4,743) = 14.652, p < 0.0001,
      Power = 1.00). The data were moderately to highly correlated. We conclude that
      the Lactate Pro is a simple and effective measurement device for taking blood
      lactate in a field or laboratory setting. However, we would caution against using
      this machine to compare data from other machines.

PMID- 11842362
TI  - Moment and power of lower limb joints in running.
AB  - The aim of this study was to test the suitability of inverse dynamics method for
      instantaneous expression of joint kinetics and muscle function with various parts
      of the ground contact when running at different speeds. Nine male runners ran at
      speeds of 4.0 m x s(-1), 6.0 m x s(-1) and at their maximal speed. 2-D video
      analysis (200-frame x s(-1)) was synchronized with 3-D ground reaction force
      measurements (10 m-long force platform). Mechanical joint power was computed from
      2-D segment dynamics associated with joint forces and net moments in multi-body
      movements. From these computations two successive functional phases during
      contact were found in the ankle and knee joints: 1) extensor negative and 2)
      extensor positive work. The hip joint showed three phases: 1) extensor positive,
      2) flexor negative and 3) flexor positive work. Peak joint power increased in
      every investigated joint with increasing running speed. The highest changes were
      observed in the hip joint: from 327 +/- 203 W at a speed of 4.0 m x s(-1) to 1642
      +/- 729 W (p < 0.01) at the maximal speed. The results may suggest that the role
      of the ankle and knee extensors is to create high joint stiffness before and
      during the contact phase, while the hip extensors are the prime forward movers of
      the body with increasing running speed. In conclusion, the inverse dynamics
      method may be of importance for use in specifying the joint kinetics and muscle
      function. However, the interpretation may become clearer when this method is used
      simultaneously with EMG measurements.

PMID- 11842363
TI  - The effect of glucose ingestion on endurance upper-body exercise and performance.
AB  - The physiological responses to glucose supplementation during arm crank exercise
      were investigated. Ten subjects of mean age 28 +/- 8 years; stature 180.8 +/- 6.5
      cm; mass 82.7 +/- 11.5 kg, .VO(2) peak 3.10 +/- 0.50 l x min(-1) were tested on
      two occasions separated by a week. A 7.6% glucose drink or placebo was
      administered in a blind crossover design 20 min prior to exercise. Subject's arm
      cranked for 60 min at an exercise intensity of 65% .VO(2)peak followed by a 20
      min performance test. Rate of ventilation, oxygen uptake, RER, heart rate and
      blood lactate demonstrated similar responses between trials throughout the course
      of the hour. The blood glucose concentrations at rest were similar between trials
      increasing after glucose ingestion to show a significant difference (p < 0.05) to
      the placebo trial at the onset of exercise, then returning to resting values
      after 20 min. The 20 min performance tests revealed that after glucose ingestion
      athletes achieved a greater mean distance of 12.55 +/- 1.29 km than in the
      placebo trial of 11.50 +/- 1.68 km (p < 0.05). In conclusion, the results showed
      that after one-hour of arm crank exercise, performance over a further twenty
      minutes was improved when glucose was ingested twenty minutes prior to exercise.

PMID- 11842364
TI  - Effect of mandibular orthopedic repositioning appliance on kinematic pattern in
      golf swing.
AB  - Experience has shown that repositioning the mandible may have an influence on the
      athletic performance. Many athletes with or without occlusal problems are now
      using mandibular orthopedic repositioning appliance (MORA) supposedly to optimize
      their performance. In golf, the players do not have any direct opponent and they
      have different clubs to reach various distances. Therefore, an automatic swing
      permits the uncertainty of the movement to be restricted. The aim of this study
      was to analyze if the use of the MORA could have an effect on the stability of
      the kinematic pattern in golf swing, connected to the capacity of the golfers to
      reproduce their swing from kinematic perspective. The measures of kinematic data
      have been established with the optoelectronic system VICON (Oxford's Metrix,
      Oxford, UK) with five cameras operating at 50 frames per second. Measurements of
      the speed of the ball at impact were obtained with a radar (Bridgestone HD.01,
      Science eye, USA). Six professional (current handicap ranging from 0 to 4) right
      handed golfers participated in the study. Six MORA were made and adjusted to fit
      each player. Each golfer performed five swings without mouthpiece and five with
      the MORA. The results of this study show that there was no difference related to
      the MORA on kinematic pattern of the golf swing. Moreover, there were significant
      differences concerning the ball speed at the impact, among the two test
      conditions, with or without the appliance (p < 0.03). The percentage of
      variability indicates that the speed with MORA was more regular than the speed
      without the appliance.

PMID- 11842365
TI  - [Ultrasonic examinations in pregnancy--a tool as good as the user].

PMID- 11842366
TI  - [Quality demands on continuing differential diagnostic sonography in prenatal
      diagnostics (DEGUM stage II) during the 18th to 22nd weeks of gestation].

PMID- 11842367
TI  - [Ultrasound examination of non-traumatic acute abdomen].
AB  - Amongst all imaging procedures available for the exploration of an acute non
      traumatic abdomen, ultrasound comprises the first line technology. Non ionising,
      easily accessible, cheap and usable at the bedside, this imaging technique also
      has the advantage of close contact with the patient, which may help to focus the
      exploration on painful regions. Moreover, ultrasound has not only diagnostic
      capabilities, but also therapeutic ones. Nevertheless, sonography has
      limitations, which have to be known in order to avoid misdiagnosis or inadequate
      reassurance. The aim of this review is to present and discuss the most recent
      opinions about ultrasound diagnosis of acute non-traumatic abdomen related to
      digestive system diseases.

PMID- 11842368
TI  - [Screening for aneuploidy by first trimester nuchal translucency measurement:
      results from a prospective trial including 1980 cases in a single center in
      Switzerland].
AB  - AIM: The purpose of this study was to evaluate the efficiency of first trimester
      screening for chromosomal abnormalities using the sonographically determined
      thickness of nuchal translucency (NT) combined with maternal age. PATIENTS AND
      METHODS: Risk screening was offered to all patients with a fetal crown rump
      length (CRL) between 45 and 84 mm after extensive counselling. For the risk
      assessment the software provided by the Fetal Medicine Foundation was used. In
      accordance with the recommendation of the Swiss Working Group on First Trimester
      Screening a cut-off risk of 1 : 400 was chosen. RESULTS: A total of 1980
      consecutive pregnancies participating in the risk screening programme with due
      dates prior to May 1, 2001 were included. Mean maternal age was 30.1 yrs and 522
      (26.4 %) patients were 35 yrs or older. A positive risk screening result was
      obtained in a total of 219 (11.1 %) pregnancies including 33 of the 37 (1.9 %)
      cases with unbalanced chromosomal abnormalities. CONCLUSIONS: The detection rate
      for unbalanced chromosome abnormalities in general (89.2 %) as well as the one
      for trisomy 21 (93.3 %) in particular are very high with a moderate false
      positive rate (9.6 %) in this series. As a comparison in the series presented
      here, traditional "maternal age screening" (cut-off age 35 yrs) would have
      yielded detection rates of 64.9 % for all unbalanced chromosome abnormalities and
      73.3 % for trisomy 21 at a false-positive rate of 25.0 %. Reducing the false
      positive rate by raising the cut-off age to 38 yrs would yield detection rates of
      40.5 % for all unbalanced chromosome abnormalities and 46.7 % for trisomy 21 at a
      false-positive rate of 8.9 %. The number of invasive procedures performed to
      detect one unbalanced chromosome count may be calculated as 21.75 using the cut
      off age of 35 yrs as compared to 6.4 using NT measurement and maternal age. The
      outcome of this ongoing study is in good accordance with the earlier observation
      that the main benefit of the addition of first trimester NT measurements to the
      risk screening protocol is a very high detection rate at a moderate false
      positive rate.

PMID- 11842369
TI  - [Ultrasound examinations in the context of suspected fetal malformations:
      satisfaction of concerned women and their appraisals].
AB  - BACKGROUND AND RESEARCH QUESTIONS: Fetal malformations can be detected at an
      early stage during pregnancy by today's ultrasound technology. This study
      examined how pregnant women appraise the application of ultrasound technology
      when a fetal malformation is suspected and how this appraisal is influenced by
      the confirmation or rejection of the diagnosis and by the subsequent course of
      the pregnancy. METHOD: In a prospective study 86 pregnant women for whom a fetal
      malformation had been suspected in an ultrasound examination were assessed at
      three points in time: before the ultrasound examination at a specialized centre,
      one to two weeks after the examination, and four weeks after giving birth or
      after the premature termination of pregnancy. Assessments were conducted by means
      of questionnaire and semi-structured interviews. RESULTS: 96.4 % of pregnant
      women advocated routine ultrasound examinations, irrespective of whether the
      suspected malformation was confirmed or not and irrespective of whether the
      pregnancy was continued or terminated prematurely. The women rated as being most
      important the medical goals of the examination (e. g. determination of the
      child's health status) and less so the subjective and personal goals (e. g.
      visualization of the child). Communicative competence in the context of the
      examination (e. g. quality of information) were judged less favourably than
      technical competence (e. g. performance of the exam). 94.2 % of the women
      believed that the cost of the ultrasound exam should be carried by health
      insurances. DISCUSSION: The findings of the study show the strong significance
      which prenatal ultrasound examinations have for pregnant women. Acceptance of
      ultrasound technology is high even when the examination results cause
      psychological stress. However, they also indicate that more attention should be
      given to aspects of communication and interaction in training and application of
      ultrasound technology.

PMID- 11842370
TI  - [Suspected fetal malformation in ultrasound examination: effects on the
      psychological well-being of pregnant women].
AB  - OBJECTIVE: Today's ultrasound technology permits the detection of foetal
      malformations during pregnancy. This study examined pregnant women's
      psychological responses to a suspected fetal anomaly and the subsequent course of
      psychological well-being. METHOD: 86 pregnant women with a suspected fetal
      malformation were assessed by means of questionnaires three times: before an
      ultrasound examination at a specialized centre, one to two weeks after the
      examination, and four weeks after giving birth or after premature termination of
      the pregnancy. Anxiety (STAI), depression (HADS-D) and feelings towards the child
      were assessed. RESULTS: A suspected fetal malformation results in psychological
      stress with anxiety and depression levels significantly higher than in normal
      samples. Regardless of either confirmation or rejection of the diagnosis of a
      malformation, stress decreases significantly after the ultrasound examination at
      the specialized centre. Only women who decide to terminate the pregnancy
      prematurely show increasing levels of stress in this period. Four weeks after
      giving birth or termination of pregnancy the assessed psychological parameters of
      all participants fall within the normal range. CONCLUSIONS: A suspected fetal
      malformation results in immediate psychological stress but not in an enduring
      psychological disorder. Women facing immediate premature termination of pregnancy
      exhibited the highest stress levels. The psychosocial distress caused by the
      diagnosis of a fetal malformation should be taken into consideration in the
      psychosocial consultation and treatment of concerned women and their partners.

PMID- 11842371
TI  - [Colonic diverticulosis: A comparison between sonography and endoscopy].
AB  - AIM: To investigate the ability of sonography to diagnose diverticulosis and to
      demonstrate the typical appearance of normal diverticula. PATIENTS AND METHODS:
      Sixty consecutive patients underwent sonography for prospective evaluation of the
      presence of diverticulosis of the left hemicolon. Diverticula were assessed for
      number, diameter, echogenicity, and wall thickness. Sonographic results were
      compared with those of endoscopy. RESULTS: Sonography yielded positive results in
      28/33 patients (85 %) with endoscopically proven diverticulosis. Sonography on
      average could demonstrate less diverticula per patient than endoscopy. Two
      sonographic results were false positive. Diverticula had a maximum average
      diameter of 8.7 mm and the diverticular wall measured 1 mm at most. In many cases
      the diverticular wall could not be demonstrated by sonography. All diverticula
      except for one were hyperechoic. In 39 % of patients with diverticulosis one or
      more diverticula showed clear acoustic shadowing indicative of a faecalith. The
      maximum diameter of the colonic wall was 3.3 mm on average. Sonography could
      demonstrate the descending colon in all cases. The sigmoid colon was not visible
      in 3 cases and could rarely be evaluated in its entire length. CONCLUSION:
      Sonography can diagnose diverticulosis of the left hemicolon in most cases.
      Normal diverticula present as hyperechoic protuberances of the colonic wall with
      acoustic shadowing of varying intensity. The diverticular wall is thin and often
      not demonstrable at sonography.

PMID- 11842372
TI  - [Ultrasonographic imaging of pneumarthrosis of the knee joint--case report and
      experimental cadaver study].
AB  - In case of penetrating injuries near to the knee joint showing only a small skin
      lesion and no damage to tendons and neuro-vascular structures, opening of the
      joint cavity has to be taken into consideration. Besides surgical revision of the
      penetration canal, radiological depiction of free intraarticular air may be
      useful. We report the cases of two patients, who suffered from intraarticular
      effusion and pain two, respectively three days after a penetrating injury. In
      both of them, free intraarticular air in the suprapatellar region could be
      depicted by ultrasonographic assessment. Subsequent evaluation of radiographs
      showed intraarticular air already being there at the day of admittance.
      Performing an experimental study in fifteen cadaver knee joint specimens, the
      reliability of this technique was evaluated and documented. Using an injection
      needle, air was insufflated into the knee joints with or without previous
      instillation of fluid. Afterwards sonographic assessment was performed using 7,5 
      13 MHz linear probes and Siemens (Elegra) equipment. Ultrasonographic detection
      of pneumarthrosis of the knee joint was possible early and reliably in both of
      the patients reported. With sufficient experience of the clinician and adequate
      equipment, even singular intraarticular air blisters are detectable, especially
      in cases of concomitant intraarticular effusion. By ultrasound it was possible to
      detect pneumarthrosis with at least 0,5 ml, by X-ray with at least 2 ml.
      Ultrasonography proved to be a reliable diagnostic tool for the detection of free
      intraarticular air within the knee joint. This fact should be considered in the
      differential diagnosis of unclear knee joint disorders after penetrating
      injuries.

PMID- 11842373
TI  - [Sonographically guided fine-needle aspiration of abscesses in cases of abdominal
      actinomycosis].
AB  - This report describes two cases of isolated abdominal actinomycosis. a) A 52-year
      old man developed a peripancreatic abscess in the course of two years after
      laparoscopic cholecystectomy and repeated laparotomy because of postoperative
      peritonitis. b) A 19-year-old man, who had a perityphlitic abscess following
      appendectomy performed because of appendicitis. The definitive diagnosis of
      abdominal actinomycosis was confirmed by percutaneous ultrasound-guided fine
      needle aspiration: In both cases culture of the aspirated material yielded
      Actinomyces (A.) israelii. As concomitant microflora we found Klebsiella and
      Actinobacter species in the first case and Haemophilus (Actinobacillus)
      actinomycetem comitans in the other case. "Sulfur granules" obtained from the pus
      showed histological aggregates of Actinomyces in both cases. After surgical
      treatment and antibiotic therapy, both patients recovered completely.

PMID- 11842374
TI  - Laryngeal osteosarcoma: a clinicopathologic analysis of four cases and comparison
      with a carcinosarcoma.
AB  - We report the clinicopathologic findings of four cases of laryngeal osteosarcoma
      and one of carcinosarcoma with osteosarcoma components. The tumors occurred in
      men ranging in age from 50 to 69 years within a median age of 63.3 years. The
      most common symptoms were hoarseness, dyspnea, and obstruction, or a combination
      of these. Biopsy material and intraoperative frozen sections usually showed a
      high-grade sarcoma, but the diagnosis of osteosarcoma was quite apparent on
      microscopic examination of the surgical specimen. The primary differential
      diagnosis is spindle cell carcinoma with osteoid formation. Pulmonary metastases
      and local recurrences were common. Surgery is the treatment of choice, followed
      by adjuvant chemotherapy. Whether to use radiotherapy or not should be decided on
      an individual basis.

PMID- 11842375
TI  - Pathology of the autonomously functioning (hot) thyroid nodule.
AB  - We describe the pathologic findings of 73 clinically and scintigraphically
      confirmed hot nodules. In general, hot nodules from an unselected group primarily
      treated by surgery were smaller and the sex ratio was closer to equality compared
      with the ample female predominance in the referral, pre-, and post-prophylaxis
      groups. Malignancy was observed in six cases (8.2%) (5 follicular, 1 papillary).
      Of the 67 benign tumors, 48 (71.6%) were adenomas which showed the
      cytoarchitectural features of hot nodules described previously, and 19 (28.3%)
      were less well-differentiated adenomas that included a few oxyphil tumors.
      Intracolloid oxalate crystals from background thyroid tissue were present in 59
      assessable cases (83%) overall, the majority showed more than occasional crystals
      that had a tendency to increase in number with decreasing morphologic activity of
      the thyroid epithelium. Thyroglobulin protein and mRNA stainings tended to be
      more pronounced in cell cytoplasm of the tumors than in background thyroid. This
      study shows that hot nodules may show a wide morphologic spectrum of follicular
      neoplasms and can be occasionally malignant. It is inferred from the morphologic
      and other findings that it is likely that some, if not all, of the primary
      follicular cancers associated with hyperfunction arise by clonal progression from
      benign hot nodules. This progression is rare, probably because most hot nodules
      present with the symptoms of hyperfunction and receive early treatment.

PMID- 11842377
TI  - Cytopathology-histopathology of the mediastinum: epithelial, lymphoproliferative,
      and germ cell neoplasms.
AB  - The last several years have witnessed an increase in reports regarding the
      pathology and classification of mediastinal neoplasms that heretofore have
      received relatively scant attention in comparison to tumors from other anatomic
      locations. Some of these, such as thymoma, remain controversial and contentious
      subjects. The sampling and diagnosis of mediastinal tumors using the technique of
      fine-needle aspiration biopsy has not gained acceptance among radiologists,
      surgeons, and pathologists to the degree it has for tumors of the thyroid or
      breast. Thus, the literature regarding aspiration cytopathology of mediastinal
      neoplasms is extremely limited. This report focuses on the salient cytopathologic
      features of epithelial, lymphoid, and germ cell tumors of the mediastinum and
      correlates the cytomorphology with their histologic equivalent.

PMID- 11842376
TI  - A method for quantifying adrenocortical nodular hyperplasia at autopsy: some use
      of the method in illuminating hypertension and atherosclerosis.
AB  - Quantifying the severity of adrenocortical nodular hyperplasia at autopsy or
      surgery has much potential practical value. For instance, this inquiry explores
      the correlation of adrenal nodularity with features of atherosclerosis in
      coronary arteries and microvascular features of hypertension in the renal cortex.
      Tissue retrieved from forensic autopsies in 96 men and women ages 16 to 88 years
      were evaluated for adrenal nodularity, coronary atheroma, and hypertensive renal
      microvasculopathies. Formalin-fixed adrenal glands were cut into 0.5-cm thick
      slices and fixed to plastic sheets with SuperGlue (Ross Products, Inc, Columbus,
      OH). After ranking the specimens on increasing nodularity, they were judged to
      fall into 10 distinguishable grades of increasing severity; photographs of a
      representative in each grade were arranged onto a panel. Each gland was then
      assigned the grade of the photograph it most resembled. Coronaries and kidneys
      were evaluated in paraffin sections. Weight and nodularity of adrenal glands
      increased with age. Men with at least one instance of atheroma in the coronary
      sample had heavier and more nodular glands (age-adjusted) than in men without
      atheroma. The differences held stronger statistical significance for nodularity
      than for weight because nodularity continued to show significance even within age
      groups sometimes represented by few cases. Hypertensive renal microvasculopathies
      failed to correlate with any of the adrenal features. Women were too few for the
      analysis. Findings made with the panel of photographs now available for grading
      adrenocortical nodular hyperplasia showed interesting correlations with coronary
      atherosclerosis in this data set, suggesting that use of this method might offer
      some insight into cardiovascular disease.

PMID- 11842378
TI  - Collision of a syncytial meningioma and malignant astrocytoma.
AB  - The coexistence of two or more primary brain tumors is a relatively rare
      occurrence. We report an 87-year-old woman with a 5-cm cystic-solid, peripherally
      enhancing, right frontal lobe mass. The woman presented with progressive
      hemiparesis, difficulty ambulating, and urinary incontinence. Histologic
      examination of the surgically excised lesion showed geographically distinct areas
      of syncytial meningioma (World Health Organization grade I) and malignant
      astrocytoma (World Health Organization grade III). Focally, infiltration of the
      meningioma by astrocytoma was observed. Differential diagnostic issues are
      considered and the literature reviewed.

PMID- 11842379
TI  - Inverted transitional cell papilloma of the uterine cervix.
AB  - A rare case of inverted transitional cell papilloma of the uterine cervix in a 54
      year-old woman is described. A polypoid nodule 8 mm in diameter showed histologic
      features similar to those of urinary tract inverted papilloma. It contained
      inverted anastomosing epithelial nests divided by scarce fibrovascular septa. The
      epithelial nests with peripheral palisading had uniform and oval nuclei with
      longitudinal grooves and swirling orientation. Significant atypia and mitotic
      activity were absent. Inside the nests there were foci of intraepithelial
      glandular metaplasia resembling glandular cystitis of the urinary bladder. MIB-1
      index was 6%, and the distribution of MIB-1-positive nuclei was similar to that
      of immature metaplasia. A recurrence-free follow-up period of 16 months along
      with a low level of proliferation assessed by histology and immunohistochemistry
      suggests a benign nature of the lesion. A review of published transitional cell
      (urothelial) lesions of the female genital tract is added.

PMID- 11842380
TI  - Gonadal tumor with granulosa cell tumor features in an adult testis.
AB  - Granulosa cell tumor is almost exclusively an ovarian tumor. Rare cases of
      granulosa cell tumor have been reported involving the testes. We report a
      testicular gonadal stromal tumor with granulosa cell differentiation in a 54-year
      old white man. The tumor was discovered by an ultrasound evaluation for left
      hydrocele. The patient was clinically asymptomatic. On frozen section, the
      initial impression was a malignant lymphoma. Final histology on the orchiectomy
      specimen showed a gonadal stromal tumor with granulosa cell features.
      Immunohistochemical studies excluded malignant lymphoma and germ cell tumors,
      consistent with a stromal tumor. This case report illustrates the challenges for
      the pathologist in making an accurate diagnosis in unusual testicular tumors.

PMID- 11842381
TI  - Hodgkin-like transformation of a marginal zone B-cell lymphoma of the larynx.
AB  - Primary larynx lymphomas, specifically of the mucosa-associated lymphoid tissue,
      are a rare but documented phenomenon. Transformation of any type of lymphoma that
      has the presence of Reed-Sternberg cells is unusual in lymph nodes and
      exceptional in extranodal sites. Herein, we report the first case (to the best of
      our knowledge in a review of the English literature [MEDLINE 1966-2001]) in which
      both of these unusual findings are present; that is, an extranodal marginal zone
      B-cell lymphoma of laryngeal mucosa-associated lymphoid tissue with Hodgkin-like
      transformation. The patient is a 78-year-old man who presented with intermittent
      shortness of breath, progressive dysphagia, and intermittent hoarseness. On
      examination, a large mass of the left supraglottic larynx was identified with a
      "ball-valve" effect into the laryngeal inlet with inspiration. Examination of the
      neck showed no palpable masses. Histologic examination of the incisional biopsy
      showed replacement of the submucosa by sheets of atypical monocytoid B cells
      (CD20+, CD79a+, lambda+, CD3-) characterized by nuclear atypia, mitotic activity,
      plasmacytoid differentiation, and restricted for lambda light chains. Dutcher
      bodies were easily identified. Interspersed throughout the neoplastic lymphoid
      population were numerous Reed-Sternberg cells and variants immunoreactive for
      CD30 and CD15 and nonreactive for CD45RB. The patient was treated with 44 cGy to
      the neck and larynx and was alive and free of disease at last contact, 2.6 years
      after the original presentation.

PMID- 11842382
TI  - The significance and etiology of intestinal metaplasia of the esophagogastric
      junction.
AB  - Biopsies from the vicinity of the esophagogastric junction occasionally show foci
      of intestinal metaplasia. Whether these biopsies represent Barrett's esophagus in
      all cases is controversial and of clinical importance because patients with
      Barrett's esophagus are at significantly increased risk for developing esophageal
      adenocarcinoma. Recent evidence suggests that intestinal metaplasia of the
      gastric cardia is also quite common. Although prospective data are relatively
      sparse, it has been suggested that the risk of progressing to dysplasia and
      adenocarcinoma is significantly lower for intestinal metaplasia of the gastric
      cardia when compared with esophageal intestinal metaplasia (Barrett's esophagus).
      Immunohistochemical stains for cytokeratins 7 and 20 may be useful in more
      precisely localizing the site of intestinal metaplasia in biopsy specimens taken
      from the vicinity of the esophagogastric junction. Correlation of all clinical,
      endoscopic, histologic, and immunohistochemical data may be used by the
      gastroenterologist to determine the likely source of the intestinal metaplasia
      and whether the patient should be followed by endoscopic surveillance.

PMID- 11842383
TI  - Rituximab: mechanism of action and resistance.
AB  - Rituximab (Rituxan; Genentech, Inc, South San Francisco, CA, and IDEC
      Pharmaceuticals, San Diego, CA)-mediated killing of CD20-positive tumor cells is
      likely caused by a combination of immune-mediated effects including complement
      mediated lysis and antibody-dependent cell-mediated cytotoxicity and direct
      effects induced by CD20 ligation. In vivo, the clearance of damaged or
      preapoptotic cells through specific receptors for phosphatidylserine translocated
      to the outer cell membrane may also be important. Direct effects, including
      growth inhibition and apoptosis, have been shown in vitro; however, their
      contribution to the clinical effect is not known. Currently, most data suggest
      that the predominant effector mechanism is antibody-dependent cell-mediated
      cytotoxicity, with a minor role of complement. With treatment, resistance to
      rituximab-mediated killing may emerge. Little is known regarding the molecular
      pathogenesis of this resistance. In rare cases, the CD20 antigen may be lost.
      Complement-resistance proteins may also increase, but it is not clear that this
      is the reason for loss of sensitivity. A better understanding of these mechanisms
      should allow combination therapy with agents capable of augmenting antibody-based
      killing.

PMID- 11842384
TI  - Modulating apoptosis pathways in low-grade B-cell malignancies using biological
      response modifiers.
AB  - Collectively, low-grade B-cell malignancies constitute the fifth most common form
      of potentially lethal cancer in North America and Europe, with chronic
      lymphocytic leukemia (CLL) and follicular non-Hodgkin's lymphoma (FL)
      representing the most prevalent of these disorders. Chronic lymphocytic leukemia
      and FL represent quintessential examples of human malignancies that are caused
      primarily by defects in programmed cell death (apoptosis). During the early
      stages of disease, the mature B lymphocytes that comprise most CLLs and FLs are
      largely quiescent G(0) phase cells, which accumulate not because they are
      dividing more rapidly than normal but because they survive longer than their
      normal counterparts because of defects in the normal pathways for apoptosis.
      Defects in apoptosis pathways contribute to chemoresistance, rendering tumor
      cells less sensitive to the cytotoxic actions of currently available anticancer
      drugs, and can also promote resistance to cellular immune responses. Several
      biological agents or their synthetic derivatives show promise as apoptosis
      modulators, having the potential to place neoplastic cells into a more
      susceptible state or activating latent programs for cell suicide. These
      biological response modifiers include monoclonal antibodies such as rituximab
      (Rituxan; Genentech, Inc, South San Francisco, CA, and IDEC Pharmaceuticals, San
      Diego, CA) that alter signal transduction pathways, cytokines such as TRAIL (Apo2
      ligand), ligands for retinoid/steroid family nuclear receptors, and small
      molecule compounds that bind and inhibit protein kinases. Knowledge about the
      mechanisms by which these agents influence apoptosis pathways in neoplastic
      diseases may suggest strategies for more effective and less toxic therapies for
      patients suffering from CLL, FL, and other malignancies.

PMID- 11842385
TI  - Rituximab as first-line and maintenance therapy for patients with indolent non
      Hodgkin's lymphoma: interim follow-up of a multicenter phase II trial.
AB  - The purpose of this study is to evaluate the activity of rituximab (Rituxan;
      Genentech, Inc, South San Francisco, CA, and IDEC Pharmaceuticals, San Diego, CA)
      in the first-line treatment of patients with indolent non-Hodgkin's lymphoma, and
      to evaluate the role of scheduled maintenance courses of rituximab in prolonging
      duration of remission. Sixty-two patients with stages II to IV indolent non
      Hodgkin's lymphoma (follicular or small lymphocytic) who had received no previous
      systemic therapy entered this multicenter, community-based trial. All patients
      received rituximab 375 mg/m(2) weekly for 4 consecutive weeks, and were evaluated
      for response at week 6. Patients who had an objective response or stable disease
      continued treatment every 6 months with repeat 4-week courses of rituximab for a
      total of four treatment courses. Interim results of this ongoing trial are
      available. When evaluated at week 6, 28 of 60 evaluable patients (47%) had
      objective response and 27 patients (45%) had minor response or stable disease.
      With further follow-up and repeat courses of rituximab, the major response rate
      increased from 47% to 65% and the complete response rate increased from 7% to
      27%. Response rates were similar in patients with follicular lymphoma and small
      lymphocytic lymphoma (63% and 66%, respectively). Median progression-free
      survival has not been reached, but will be greater than 24 months. There has been
      no cumulative toxicity observed with repeat courses of rituximab. Rituximab is
      highly effective as a first-line single agent for the treatment of indolent non
      Hodgkin's lymphoma. The initial response rate can be improved by using scheduled
      maintenance courses of rituximab administered every 6 months. Final information
      regarding duration of response and time to progression awaits further follow-up.

PMID- 11842386
TI  - Rituximab in the treatment of diffuse large B-cell lymphomas.
AB  - A review of the use of rituximab (Rituxan; Genentech, Inc, South San Francisco,
      CA, and IDEC Pharmaceuticals, San Diego, CA) in diffuse large B-cell lymphomas is
      presented, focusing on the recent presentation of the combination of CHOP
      (cyclophosphamide/doxorubicin/vincristine/prednisone) plus rituximab in elderly
      patients. This combination increased the response rates, event-free survival, and
      overall survival of patients older than 60 years in comparison with CHOP alone.
      The toxic events observed with the combination were not more numerous or severe
      than those observed with CHOP alone. Rituximab is a chimeric anti-CD20 antibody
      that increases the treatment options in patients with B-cell lymphomas.

PMID- 11842387
TI  - Rituximab in combination with CHOP or fludarabine in low-grade lymphoma.
AB  - Non-Hodgkin's lymphoma (NHL) is composed of a group of lymphoid malignancies that
      has been increasing in incidence at an annual rate of 4% to 7% over the last 20
      years in both the United States and Europe. The reasons for this rise in
      incidence in NHL are not yet defined but most likely involve environmental
      exposures. Low-grade and follicular lymphomas account for approximately 40% of
      the incidences of NHL in the United States. While patients with intermediate- and
      high-grade lymphomas are potentially curable with combination chemotherapy, low
      grade and follicular lymphomas are still considered to be essentially incurable
      with standard therapy. Although low-grade lymphomas characteristically respond
      well to treatment with chemotherapeutic agents, the disease typically follows a
      course of recurrent relapse and progressively shorter remissions, and ultimately
      death from lymphoma. Median survival for patients with low-grade lymphoma is 6.2
      years from diagnosis and just 5 years from time of first relapse. Therefore,
      novel therapeutic strategies are urgently needed for these patients. One approach
      to the development of innovative strategies for treatment of NHL has been the
      generation of monoclonal antibodies to specific B-cell antigens expressed on NHL
      cells.

PMID- 11842388
TI  - The role of rituximab and chemotherapy in aggressive B-cell lymphoma: a
      preliminary report of dose-adjusted EPOCH-R.
AB  - Accumulating evidence suggests that the ability to activate apoptotic pathways
      may be an important determinant of chemotherapy sensitivity and presents a
      potentially important new therapeutic strategy. Monoclonal antibodies against the
      CD20 antigen directly induce apoptosis and may serve to modulate the threshold
      for chemotherapy-induced apoptosis. Rituximab (Rituxan; Genentech, Inc, South San
      Francisco, CA, and IDEC Pharmaceuticals, San Diego, CA), a monoclonal antibody
      against CD20, was combined with dose-adjusted EPOCH (infusional
      etoposide/vincristine/doxorubicin/bolus cyclophosphamide/prednisone) chemotherapy
      and tested in 38 untreated or relapsed poor-prognosis aggressive lymphomas.
      Twenty-three patients were untreated. Of these patients, all had large B-cell
      histologies, a median age of 52 years, Eastern Cooperative Oncology Group
      performance status > or = 2 in 30%, and high-intermediate or high International
      Prognostic Index scores in 61%. Fifteen patients had relapsed or refractory
      lymphomas. These patients had received a median of two (range, one to four) prior
      regimens, 67% had aggressive histologies, and 60% had high-intermediate or high
      International Prognostic Index scores. Complete remissions were achieved in 85%
      and 64% of untreated and previously treated patients, respectively; additionally
      42% of patients with disease refractory before therapy achieved complete
      remission. At a median follow-up of 12 months, progression-free and overall
      survival in the previously untreated group was 85% and 79%, respectively, and no
      patient in complete remission has relapsed. These results suggest that rituximab
      may modulate the sensitivity of B-cell lymphomas to chemotherapy.

PMID- 11842389
TI  - Quantitative real-time polymerase chain reaction for monitoring minimal residual
      disease in patients with advanced indolent lymphomas treated with rituximab,
      fludarabine, mitoxantrone, and dexamethasone.
AB  - Fludarabine and rituximab (Rituxan; Genentech, Inc, South San Francisco, CA, and
      IDEC Pharmaceuticals, San Diego, CA) are active against indolent lymphomas. We
      have previously shown the safety and efficacy of the combination of FND
      (fludarabine/mitoxantrone/dexamethasone) in relapsed and subsequently untreated
      patients with stage IV indolent lymphomas. Currently, we treat patients with
      stage IV indolent lymphomas who are previously untreated, younger than 60 years,
      human immunodeficiency virus-negative, and have adequate organ and marrow
      function with FND and random assignment to concurrent or delayed administration
      of rituximab. We have developed a quantitative real-time polymerase chain
      reaction assay for t(14;18). With 1 microg of DNA, this assay detects 0.6 copies
      in 55% of reactions, as expected for the Poisson distribution. When 1microg of
      DNA was analyzed in duplicate, cells with the t(14;18) were detected in
      peripheral blood of 22% of 152 volunteer blood donors. Quantitation showed that
      numbers of t(14;18) cells were higher than the statistical upper normal limit
      (mean of all volunteer values plus standard deviations) in 2% of volunteer blood
      donors. By contrast, 36% of blood or marrow specimens from follicular lymphoma
      patients were positive, and the number of cells with t(14;18) was higher than the
      normal upper limit in 26%. The presence of cells with t(14;18) and their numbers
      are prospectively quantitated in blood and marrow of patients treated with FND
      plus rituximab to determine their clinical significance both at presentation and
      during therapy.

PMID- 11842390
TI  - Immunotherapy with rituximab following high-dose therapy and autologous stem-cell
      transplantation for mantle cell lymphoma.
AB  - Advanced-stage mantle cell lymphoma (MCL) is a disease for which no curative
      treatment strategy exists. Results with standard combination chemotherapy, with
      or without an anthracycline, are disappointing, and new and better therapies are
      needed. High-dose therapy and autologous stem-cell transplantation (ASCT) have
      been performed in patients with MCL both up front and at relapse with varying
      degrees of success. Rituximab (Rituxan; Genentech, Inc, South San Francisco, CA,
      and IDEC Pharmaceuticals, San Diego, CA) has shown moderate response rates in
      patients with MCL. It has also been used safely and effectively as an in vivo
      purge during ASCT for patients with lymphoma. We are currently investigating an
      aggressive protocol in patients with newly diagnosed, untreated MCL using a
      combination of two promising therapeutic modalities, high-dose therapy-ASCT and
      rituximab. Since 1999, 13 patients with newly diagnosed MCL have been enrolled in
      this phase II clinical trial. CHOP
      (cyclophosphamide/prednisone/vincristine/doxorubicin) is used as debulking
      chemotherapy. Stem cells are mobilized with 5 days of granulocyte colony
      stimulating factor 10 microg/kg/d, with a single infusion of rituximab 375
      mg/m(2) used as an in vivo purge before stem-cell collection by large-volume
      leukapheresis. The transplant conditioning regimen is
      cyclophosphamide/carmustine/etoposide. Post-transplant consolidative
      immunotherapy consists of rituximab 375 mg/m(2), administered as two 4-week
      cycles at 2 and 6 months post-transplant. So far, 12 patients (7 men/5 women)
      with a median age of 55 years (range, 41 to 65 years) have been transplanted.
      Patients were first assessed and then transplanted a median of 40 and 201 days,
      respectively, from diagnosis. International Prognostic Index at diagnosis was low
      (n = 3), low-intermediate (n = 8), and high-intermediate (n = 1). A median of six
      cycles of CHOP was required to debulk tumor sufficiently for transplant. Response
      to CHOP was 100% with six complete responses, one complete response unconfirmed,
      and five partial responses. Transplantation was well tolerated. Patients
      engrafted quickly, with a median of 11.5 days to neutrophil engraftment and 10
      days to platelet independence. Patients had modest transfusion requirements,
      requiring a median of four units of packed red blood cells and two and a half
      platelet transfusions. Six to 8 weeks post-transplant, six patients were in
      complete response, four in complete response unconfirmed, and two in partial
      response. Eight patients have received all eight maintenance rituximab
      treatments, and four have received only their first cycle. Following rituximab,
      the two patients in partial response and two in complete response unconfirmed
      converted to complete response. With a median follow-up of 239 days from
      transplant (range, 61 to 727 days), all patients remain alive and well with no
      documented relapses. Samples for molecular monitoring have been drawn from the
      stem-cell graft, and serially from the peripheral blood and bone marrow of
      patients at baseline, preapheresis, pretransplant, and post-transplant at 3-month
      intervals. This data shows that ASCT followed by rituximab immunotherapy is
      feasible and safe in patients with MCL. Although patient numbers are low and
      follow-up time is short, preliminary results are encouraging. Rituximab may
      convert partial responders to complete responders. The durability of responses
      will be determined with longer follow-up.

PMID- 11842391
TI  - Emerging information on the use of rituximab in chronic lymphocytic leukemia.
AB  - Rituximab (Rituxan; Genentech, Inc, South San Francisco, CA, and IDEC
      Pharmaceuticals, San Diego, CA) is a chimeric monoclonal antibody that targets
      mature B cells in most lymphoid B-cell malignancies. While rituximab was approved
      by the US Food and Drug Administration for the treatment of recurrent B-cell
      lymphoma, initial studies suggested that it had less activity in small
      lymphocytic lymphoma, the nodal counterpart of chronic lymphocytic leukemia
      (CLL). Two studies have now investigated the activity of higher-dose and more
      intensive therapy with rituximab in CLL. They have shown a dose-response
      relationship and a higher response rate than previously seen in the lower-dose
      studies. This is presumably caused by the overcoming of lower antigen density on
      CLL cells compared with lymphoma cells, and the shorter half-life of rituximab in
      small lymphocytic lymphoma. There is now evidence that CD20 is shed into the
      plasma in patients with CLL, which may explain the shorter half-life of the
      antibody in small lymphocytic lymphoma/CLL. The higher dose may then be effective
      in overcoming this so-called "antigen sink." Toxicity was uncommon except in
      previously untreated patients and those with atypical forms of CLL such as mantle
      cell lymphoma and prolymphocytic leukemia. There is now evidence in vitro of
      additive or synergistic activity of rituximab with a variety of chemotherapeutic
      agents including fludarabine and cyclophosphamide. Combinations of fludarabine
      with rituximab or these two drugs combined with cyclophosphamide have given very
      high complete response rates in series of patients with both previously untreated
      and treated CLL. It is apparent that rituximab is playing a significant role in
      the management of patients with CLL as salvage therapy and is a potential
      potentiating agent for combined chemoimmunotherapy strategies for front-line or
      relapsed patients with CLL.

PMID- 11842392
TI  - Conceptual aspects of combining rituximab and Campath-1H in the treatment of
      chronic lymphocytic leukemia.
AB  - Monoclonal antibody-based therapy has emerged as a novel approach in the
      treatment of hematologic malignancies. The safety and tolerability of monoclonal
      antibodies make these compounds attractive and easy to administer, even in
      elderly, heavily pretreated patients. Chronic lymphocytic leukemia is an
      incurable disease with few therapeutic options once patients fail purine analogue
      based therapy. Two monoclonal antibodies have shown activity in this disease. The
      first is rituximab (Rituxan; Genentech, Inc, South San Francisco, CA, and IDEC
      Pharmaceuticals, San Diego, CA), a chimeric human-mouse anti-CD20 antibody. The
      second is Campath-1H, a humanized form of a rat antibody active against CD52. We
      hypothesize that combining both antibodies in patients who have failed
      conventional therapies and express both CD20 and CD52 might have enhanced
      efficacy and therapeutic benefit. This concept is being explored at our
      institution in the context of a phase I/II clinical trial. The outcome and
      feasibility of this combination opens the way for future combination therapies
      using novel biologic agents.

PMID- 11842393
TI  - Immunotherapy of non-Hodgkin's lymphoma with hLL2 (epratuzumab, an anti-CD22
      monoclonal antibody) and Hu1D10 (apolizumab).
AB  - Clinical activity of anti-CD20 monoclonal antibodies both in the unlabeled
      (rituximab [Rituxan; Genentech, Inc, South San Francisco, CA, and IDEC
      Pharmaceuticals, San Diego, CA]) and radiolabeled forms, as well as
      radioimmunoconjugates targeting other antigens, has resulted in the exploration
      of alternative targets for immunotherapeutic strategies in lymphoma. We report on
      the rationale for and initial efforts in the development of two unlabeled,
      humanized monoclonal antibodies directed against molecules commonly expressed in
      B-cell malignancies. hLL2 (epratuzumab; Immunomedics, Inc, Morris Plains, NJ)
      binds to the CD22 antigen, while Hu1D10 (apolizumab; Protein Design Labs, Inc,
      Fremont, CA) reacts with a polymorphism on the HLA-DR beta chain. Preclinical
      studies and early clinical evaluations suggest that these agents have a potential
      role as novel therapeutic targets for lymphoma with acceptable toxicity profiles.
      Further efforts will explore optimal clinical settings for their use, as well as
      define treatment regimens either as single agents or in combination with
      chemotherapy or other biologics.

PMID- 11842394
TI  - Yttrium 90 ibritumomab tiuxetan radioimmunotherapy for relapsed or refractory low
      grade non-Hodgkin's lymphoma.
AB  - The treatment of malignant lymphoma has improved over the past 20 years, but the
      majority of patients are not cured. New modalities using targeted therapy based
      on new information in molecular biology and immunology hold promise for better
      outcomes with less toxicity. We review data on the use of radiolabeled monoclonal
      antibodies directed against the CD20 antigen on malignant B cells. We discuss the
      major radionuclides available, iodine 131 ((131)I), tositumomab, and yttrium 90
      ((90)Y) ibritumomab tiuxetan (Zevalin; IDEC Pharmaceuticals, San Diego, CA) and
      present data on new approaches in labeling antibodies that have facilitated their
      use. Clinical trial data with the yttrium-labeled antibodies are discussed. The
      use of dosimetry as a means for predicting toxicity is discussed, and the
      questions of long-term toxicity (late effects) are addressed. These targeted
      approaches to the treatment of malignancy, and lymphoma in particular, hold great
      promise.

PMID- 11842395
TI  - Synergism between cytosine-guanine oligodeoxynucleotides and monoclonal antibody
      in the treatment of lymphoma.
AB  - Synthetic oligodeoxynucleotides containing unmethylated cytosine-guanine
      dinucleotides (CpG ODN) are potent immunostimulatory agents that can activate
      various immune cell subsets. We have found that CpG ODN show a variety of effects
      that could be useful in enhancing the efficacy of antibody therapy of lymphoma.
      In a mouse model, CpG ODN alone had no effect on survival of animals inoculated
      with lymphoma. In contrast, CpG ODN plus monoclonal antibody (MAb) was more
      effective at inhibiting tumor growth than MAb alone or MAb plus control ODN.
      Cytosine-guanine ODN plus MAb cured mice with a large tumor burden that could not
      be cured with MAb therapy alone. We also evaluated the effects of CpG ODN on the
      phenotype of human malignant B cells. Cytosine-guanine ODN upregulated the
      expression of a number of antigens, including CD20. The upregulation of CD20 was
      most extensive in cells that had low baseline expression of this antigen. We
      conclude that CpG ODN enhances the efficacy of MAb in a murine lymphoma model,
      most likely by activating effector cells, and upregulates expression of CD20 on
      primary human malignant B cells. Given the effects of CpG ODN on both target
      antigen expression and effector-cell function, further evaluation of the
      combination of CpG ODN plus rituximab (Rituxan; Genentech, Inc, South San
      Francisco, CA, and IDEC Pharmaceuticals, San Diego, CA) and CpG ODN plus other
      MAbs is warranted.

PMID- 11842396
TI  - Advances in classification and therapy of indolent B-cell malignancies.
AB  - Advances in our understanding of normal B-cell differentiation have allowed for
      improved classification and therapy of B-cell malignancies. B-cell neoplastic
      diseases may be classified more accurately according to the differentiation
      stages of presumed normal B-cell counterparts. These advances have challenged the
      notion that chronic lymphocytic leukemia represents a malignancy of naive CD5 B
      cells. Analyses of immunoglobulin genes and gene expression patterns through
      microarray have defined at least two types of chronic lymphocytic leukemia that
      differ in their tendency toward disease progression. Nevertheless, these types
      still share more in common than they do with other lymphoid malignancies, and
      both may be derived from memory-type B cells. Advances in immune therapy are
      revolutionizing the approach to therapy. B-cell surface differentiation antigens
      constitute tissue-specific targets for passive immune therapy. Since the US Food
      and Drug Administration approval of rituximab (Rituxan; Genentech, Inc, South San
      Francisco, CA, and IDEC Pharmaceuticals, San Diego, CA) for use in the treatment
      of follicular lymphoma, monoclonal antibody therapy is being considered for all
      types of B-cell malignancies. The ability to transform leukemia and lymphoma B
      cells into effective antigen-presenting cells through CD40 ligation allows for
      autologous immune recognition of neoplastic cells. Together, active and passive
      immune approaches have potential for effective treatment of patients with these
      diseases.

PMID- 11842397
TI  - Rituximab: ongoing and future clinical development.
AB  - Monoclonal antibodies have been used as therapeutic agents for many years. In
      1997, rituximab (Rituxan; Genentech, Inc, South San Francisco, CA, and IDEC
      Pharmaceuticals, San Diego, CA) became the first monoclonal antibody to be
      approved by the US Food and Drug Administration for a cancer indication. The use
      of rituximab in the treatment of low-grade or follicular, relapsed, or refractory
      CD20-positive B-cell non-Hodgkin's lymphoma was approved in November 1997 for
      United States marketing under the trade name Rituxan. In June 1998, rituximab was
      approved for all European Union countries under the trade name MabThera as
      therapy for patients with stage III/IV, follicular, chemoresistant, or relapsed
      (> or = 2 relapses) non-Hodgkin's lymphoma. To date, rituximab has been approved
      in 56 countries. Over 125,000 patients have been treated with this antibody in
      the United States alone. Rituximab served to heighten interest in the therapeutic
      applications of monoclonal antibodies. Literally dozens of antibodies are
      currently under investigation for a variety of malignant and non-neoplastic
      indications. The US Food and Drug Administration approved a new (revised) package
      insert in early 2001. These revisions have been communicated to physicians via a
      "Dear Doctor Letter" and will appear in the 2002 edition of the Physicians' Desk
      Reference. A significant amount of clinical research has been performed over the
      past 9 years, which has served to further our understanding of the potential
      clinical applications for this novel therapeutic agent. Ongoing and future
      clinical trials are reviewed in this article. However, much remains to be
      accomplished in key areas such as combinations with chemotherapy, biologics
      (including other antibodies), and radiotherapy/radioimmunotherapy; its role
      within multimodality regimens; and other malignant (beyond low-grade non
      Hodgkin's lymphoma) and nonmalignant applications.

PMID- 11842399
TI  - Variability of metapodials in primates with rudimentary digits: Ateles geoffroyi,
      Colobus guereza, and Perodicticus potto.
AB  - A tenet of evolutionary theory is that, within a species, phenotypic variability
      is inversely related to the intensity of stabilizing selection. A corollary is
      that a rudimentary or vestigial structure should be highly variable. This
      relationship between rudimentation and variability, however, may simply be part
      of a continuum, as several studies have shown that variability and size of a
      structure are inversely related. This study tests whether the first metacarpal
      (MC1) in Ateles geoffroyi and Colobus guereza and the second metacarpal (MC2) in
      Perodicticus potto are highly variable in their lengths relative to their other
      metapodials. The former two species have rudimentary thumbs, and the latter
      species has a rudimentary index finger. Fourteen other species of primates are
      included in the comparison. The results show that MC1 in A. geoffroyi and C.
      guereza and MC2 in P. potto are the relatively shortest first and second
      metapodials, respectively, in this sample of primates. However, an intraspecific
      analysis shows that neither MC1 in A. geoffroyi and C. guereza nor MC2 in P.
      potto is significantly more variable than the other metapodials. Nevertheless, an
      interspecific analysis shows that MC1 in A. geoffroyi and C. guereza is
      relatively the most variable among the first metapodials (i.e., MC1 and first
      metatarsal) in this study. MC2 in P. potto, however, is of relatively low
      variability compared with the other primates. These contrasting results are
      interpreted in terms of the developmental and evolutionary biology of digits.

PMID- 11842400
TI  - Finger length and distal finger extent patterns in humans.
AB  - The fingers in the adult human hand differ in length and in distal extent. The
      literature agrees that in the clear majority of males, the distal extent of the
      ring finger tends to be relatively greater (using the middle finger as standard)
      than the index finger. However, the results for females vary considerably, with
      some studies reporting that females show a similar pattern to that of males,
      while others suggest that the prevalence of a longer index finger is relatively
      or absolutely more common in females. We provide a review of the literature, and
      a set of data for both finger length and distal fingertip extent of the finger
      for a contemporary cohort of young adult females and males (n = 502). Finger
      length measures favor the ring finger of both sexes, with smaller between-finger
      differences for females than for males. However, while the distal fingertip
      extent favors the ring finger of both hands in males, in females the left hand
      shows no significant differences, and the right hand shows a small index finger
      advantage. Thus, the sexual dimorphism in finger measures is more strongly
      expressed in the distal extent of fingertips than in the length of fingers. The
      sex differences in distal fingertip extent derive from the index finger only,
      with a lesser distal extent of the index finger, relative to the middle finger,
      in males than in females.

PMID- 11842401
TI  - Morphological and hormonal parameters in two species of macaques: impact of
      seasonal breeding.
AB  - To compare physiological and developmental differences between two cogeneric
      species that differ by seasonal vs. aseasonal breeding, values for morphological
      measurements, testicular volume, serum testosterone, estradiol, and
      dehydroepiandrosterone-sulfate levels were obtained from 53 rhesus during the
      early breeding season, as well as 41 pig-tailed macaque males maintained at the
      Tulane Primate Center. The two species exhibited similar body size, testosterone,
      and estradiol levels, but differed substantially in testicular volume (3.00 +/-
      1.7 vs. 1.72 +/- 1.3 cc), abdominal skinfold measures (15.7 +/- 9.2 vs. 9.0 +/-
      7.7 mm), and DHEA-S levels (18.0 +/- 11.7 vs. 7.6 +/- 5.4 microg/dl). Significant
      interaction effects for species by age group were found for weight, tricep
      circumference, length, and estradiol level. In addition, length was more closely
      related to testicular volume among rhesus compared to pig-tailed macaques,
      suggesting different developmental patterns between the species. Predictors of
      hormonal levels differed between the two species. In the rhesus, estradiol levels
      were related to testicular volume and testosterone levels while there were no
      anthropometric predictors of testosterone or DHEA-S. For the pig-tailed macaques,
      testicular volume was related to tricep circumference, testosterone to triceps
      skinfold and testicular volume, and estradiol to weight. It is argued that rhesus
      have larger testes for body size and more abdominal fat deposits during the early
      breeding season relative to pig-tailed macaques reflecting the increased demands
      of sperm competition in a seasonally breeding species. Hormonal differences
      associated with the difference in breeding system appear to be primarily related
      to adrenal rather than testicular activity.

PMID- 11842402
TI  - Factors affecting the work productivity of Oraon agricultural laborers of
      Jalpaiguri district, West Bengal.
AB  - In developing countries like India, where the incidence of protein-calorie
      malnutrition is high and mechanization is at a minimum, human labor provides much
      of the power for physical activity. This study presents anthropometric
      measurements, somatotypes, food intakes, energy expenditures, and work outputs of
      Oraon agricultural laborers of the Jalpaiguri district, West Bengal, in an
      attempt to identify the factors that predict high work productivity.
      Specifically, this study investigates 1) the relationship between morphological
      variation (anthropometric measurements and somatotype) and work productivity, 2)
      the nature and extent of the relationship between nutritional status and work
      productivity, and 3) the best predictor variables of work output. Classification
      of groups on the basis of median values of work output show that in the
      aggregate, the high productive groups are significantly younger than low
      productive groups in both sexes. Before age-adjustment, the high productive
      groups show higher mean values of a few body dimensions, though these differ by
      sex, and both males and females exhibit a normal range of blood pressure and
      pulse rate values. Mean values of grip strength and back strength are higher in
      high-output men and women. Mean values of both food intake and energy expenditure
      are also higher among men in high-output groups, with only food intake higher in
      high-output women. However, after eliminating the effects of age, the differences
      between low-productive groups and high-productive groups in most of the variables
      are not significant. Productivity predictors in males consist of age, food intake
      and chest girth (inhalation). Females, on the other hand, show age and grip
      strength (left) as work output predictors.

PMID- 11842403
TI  - Thin-plate spline analysis of allometry and sexual dimorphism in the human
      craniofacial complex.
AB  - The relationship between allometry and sexual dimorphism in the human
      craniofacial complex was analyzed using geometric morphometric methods. Thin
      plate splines (TPS) analysis has been applied to investigate the lateral profile
      of complete adult skulls of known sex. Twenty-nine three-dimensional (3D)
      craniofacial and mandibular landmark coordinates were recorded from a sample of
      52 adult females and 52 adult males of known age and sex. No difference in the
      influence of size on shape was detected between sexes. Both size and sex had
      significant influences on shape. As expected, the influence of centroid size on
      shape (allometry) revealed a shift in the proportions of the neurocranium and the
      viscerocranium, with a marked allometric variation of the lower face. Adjusted
      for centroid size, males presented a relatively larger size of the nasopharyngeal
      space than females. A mean-male TPS transformation revealed a larger piriform
      aperture, achieved by an increase of the angulation of the nasal bones and a
      downward rotation of the anterior nasal floor. Male pharynx expansion was also
      reflected by larger choanae and a more posteriorly inclined basilar part of the
      occipital clivus. Male muscle attachment sites appeared more pronounced. In
      contrast, the mean-female TPS transformation was characterized by a relatively
      small nasal aperture. The occipital clivus inclined anteriorly, and muscle
      insertion areas became smoothed. Besides these variations, both maxillary and
      mandibular alveolar regions became prognathic. The sex-specific TPS deformation
      patterns are hypothesized to be associated with sexual differences in body
      composition and energetic requirements.

PMID- 11842404
TI  - Nuclear and mitochondrial genetic variation in the Yanomamo: a test case for
      ancient DNA studies of prehistoric populations.
AB  - Ancient DNA provides a potentially revolutionary way to study biological
      relationships in prehistoric populations, but genetic patterns are complex and
      require careful interpretation based on robust, well-tested models. In this
      study, nuclear and mitochondrial markers were compared in the Yanomamo, to assess
      how well each data set could differentiate among closely related groups. The
      villages selected for the study share a recent fission history and are closely
      related to each other, as would likely be the case among prehistoric peoples
      living in the same valley or region. The Yanomamo generally practice village
      level endogamy, but some migration and gene flow are known to occur between
      villages. Nuclear and mitochondrial DNA data were compared using F-statistics and
      genetic distance analyses. The nuclear data performed as expected, males and
      females from the same village were similar, and the villages were genetically
      distinct, with the magnitude of genetic differences correlated with historical
      relationship. However, mtDNA analyses did not yield the expected results. The
      genetic distances between villages did not correlate with historical
      relationship, and the sexes were significantly different from each other in two
      villages. Both the Lane and Sublett and the Spence methods, used to test for
      archaeological residence patterns, were consistent with endogamy. Hence, ancient
      DNA can, in principle, provide us with a unique opportunity to study genetic
      structure and gene flow in archaeological populations. However, interpretations,
      particularly those based on single loci such as mitochondrial DNA, should be
      cautious because sex-specific migration and sampling issues may have dramatic
      effects.

PMID- 11842405
TI  - Discerning evolutionary processes in patterns of tamarin (genus Saguinus)
      craniofacial variation.
AB  - Quantitative genetic theory specifies evolutionary expectations for morphological
      diversification by genetic drift in a monophyletic clade. If genetic drift is
      responsible for the evolutionary morphological diversification of a clade,
      patterns of within- and between-taxon morphological variance/covariance should be
      proportional. We tested for proportionality of within- and between-species
      craniofacial morphological variation in 12 species of tamarins (genus Saguinus).
      We found that within- and between-taxon morphological variations across the
      entire genus were not proportional, and hence not likely to be due to genetic
      drift alone. The primary deviation from proportionality is that size and size
      related shape in the cranium is more variable relative to other aspects of
      cranial morphology than expected under genetic drift, suggesting differential
      size selection between the two major clades, the small-bodied and large-bodied
      tamarins. Within each of these major clades, most of the interspecific variation
      is consistent with the pattern expected under genetic drift, although specific
      contrasts may indicate the involvement of differential selection. Morphological
      distances among taxa do not correspond very closely to the phylogeny derived from
      mtDNA. In particular, S. oedipus and S. geoffroyi are very distinct
      morphologically from the rest of the tamarins, although they are phylogenetically
      the sister clade to a clade containing S. midas and S. bicolor. Morphological
      similarity is not a good guide to phylogenetic affinity in the tamarins,
      especially with regard to deeper nodes in the phylogenetic tree.

PMID- 11842406
TI  - Technical note: CT-guided biopsy: A new diagnostic method for paleopathological
      research.
AB  - The aim of this paper was to demonstrate the application of computerized
      tomographic (CT)-guided biopsy in a paleopathological examination. Researchers
      dealing with such special tasks should be aware of this method. We performed a CT
      guided percutaneous biopsy of an ancient Egyptian child mummy, which allowed us
      to revise its initial diagnosis. Based on this experience, extended
      preinterventional planning and the choice of equipment (needle type) preferred by
      performing radiologists are strongly recommended, since they will influence
      diagnostic outcome. Easy documentation, suitable approaches according to the
      object's condition, and a reliable anatomical orientation without superposition
      effects during the procedure are some of the advantages of this method. It its
      already widely established in clinical practice. This technique is recommended
      for future tissue-sampling of human paleopathologic remains like mummies that are
      still wrapped within their original bandages, or any small bone lesion of unclear
      etiology.

PMID- 11842408
TI  - Medical applications of Raman spectroscopy: from proof of principle to clinical
      implementation.
AB  - Raman spectroscopy has recently been applied ex vivo and in vivo to address
      various biomedical issues such as the early detection of cancers, monitoring of
      the effect of various agents on the skin, determination of atherosclerotic plaque
      composition, and rapid identification of pathogenic microorganisms. This leap in
      the number of applications and the number of groups active in this field has been
      facilitated by several technological advancements in lasers, CCD detectors, and
      fiber-optic probes. However, most of the studies are still at the proof of
      concept stage. We present a discussion on the status of the field today, as well
      as the problems and issues that still need to be resolved to bring this
      technology to hospital settings (i.e., the medical laboratory, surgical suites,
      or clinics). Taken from the viewpoint of clinicians and medical analysts, the
      potential of Raman spectroscopic techniques as new tools for biomedical
      applications is discussed and a path is proposed for the clinical implementation
      of these techniques.

PMID- 11842410
TI  - Vibrational coupling as diagnostic for intramolecular hydrogen bonds of
      carbohydrates in aqueous solution.
AB  - The coupling of nuC-O and deltaO-D vibrations in the 1200-900 cm(-1) IR range
      leads to band shifting in opposite directions, which provides information on
      intramolecular hydrogen bonding of carbohydrates in aqueous solution. The aqueous
      solution IR spectra of 2-acetamide-1,6-anhydro-2-deoxy-D-glucopyranose and cis
      1,2-cyclopentanediol and tetrahydrofuran-ethanol mixtures are reported. Frequency
      upshifting upon deuteration is observed for the nuC-O bands of both a hydrogen
      bond acceptor and donor in ether-hydroxyl and hydroxyl-hydroxyl contacts. The
      1200-900 cm(-1) range can be used to reveal the presence of intramolecular
      hydrogen bonds in aqueous carbohydrates, unlike the OH stretching region, which
      cannot be used in this sense due to carbohydrate band masking by the strong nuOH
      IR absorption of water.

PMID- 11842409
TI  - Changes in protein conformation and dynamics upon complex formation of brain
      derived neurotrophic factor and its receptor: investigation by isotope-edited
      Fourier transform IR spectroscopy.
AB  - The interactions of brain-derived neurotrophic factor (BDNF) with the
      extracellular domain of its receptor (trkB) are investigated by employing isotope
      edited Fourier transform IR (FTIR) spectroscopy. The protein secondary structures
      of individual BDNF and trkB in solutions are compared with those in their
      complex. The temperature dependence of the secondary structures of BDNF, trkB,
      and their complex is also investigated. Consistent with the crystal structure, we
      observe by FTIR spectroscopy that BDNF in solution contains predominantly beta
      strands (approximately 53%) and relatively low contents of other secondary
      structures including beta turns (approximately 16%), disordered structures
      (approximately 12%), and loops (approximately 18%) and is deficient in alpha
      helix. We also observe that trkB in solution contains mostly beta strands (52%)
      and little alpha helix. Conformational changes in both BDNF and trkB are observed
      upon complex formation. Specifically, upon binding of BDNF, the conformational
      changes in trkB appear to involve mostly beta turns and disordered structures
      while the majority of the beta-strand conformation remains unchanged. The IR data
      indicate that some of the disordered structures in the loop regions are likely
      converted to beta strands upon complex formation. The FTIR spectral data of BDNF,
      trkB, and their complex indicate that more amide NH groups of trkB undergo H-D
      exchange within the complex than those of the ligand-free receptor and that the
      thermal stability of trkB is decreased slightly upon binding of BDNF. The FT
      Raman spectra of BDNF, trkB, and their complex show that the six intramolecular
      disulfide bonds of trkB undergo significant conformational changes upon binding
      of BDNF as a result of changes in the tertiary structure of trkB. Taken together,
      the FTIR and Raman data are consistent with the loosening of the tertiary
      structure of trkB upon binding of BDNF, which leads to more solvent exposure of
      the amide NH group and decreased thermal stability of trkB. This finding reveals
      an intriguing structural property of the neurotrophin ligand-receptor complex
      that is in contrast to other ligand-receptor complexes such as a cytokine
      receptor complex that usually shows protection of the amide NH group and
      increased thermal stability upon complex formation.

PMID- 11842411
TI  - Physical properties of compounds promoting oral delivery of macromolecular drugs.
AB  - The spectroscopic and solution properties of a series of amidated acids (delivery
      agents), which promote the gastrointestinal absorption of USP heparin and other
      drugs that show poor oral bioavailability, are investigated using Raman and NMR
      spectroscopy. The results show evidence for self-association at low
      concentrations of delivery agents that increases as the concentration of the
      delivery agent is increased. The self-associate is characterized by ring-ring
      stacking interactions, and the best geometrical arrangement for the stacking is
      the parallel-shifted arrangement of the rings. In addition, the amide group
      participates in the formation of intermolecular hydrogen bonds in the self
      associate. Unlike the rigid ring, the tails of these delivery agents remain
      relatively flexible in the self-associate. It is suggested that the limited
      solubility of the delivery agents at physiological pH arises from a percentage of
      protonated carboxyls. Their presence promotes the formation of intermolecular
      hydrophobic and ring stacking interactions, which are otherwise weakened by an
      ionized carboxyl group.

PMID- 11842412
TI  - Interactions of amidated acids with heparin.
AB  - Raman and NMR studies are performed to characterize the solution structures of
      complexes between heparin and a group of amidated acids, which act as delivery
      agents that facilitate the gastrointestinal absorption of orally administered
      heparin. At concentrations typically employed for the oral drug delivery of
      heparin, the contact points between heparin complexed with the delivery agents
      include points near the OH groups of heparin. The results suggest that heparin
      interacts rather nonspecifically with the amidated acids as monomers and with
      self-associated complexes of the delivery agents. It is also found that the
      carboxyl groups of at least one of the bioactive delivery agents easily
      protonates when it forms complexes with itself or heparin. This attribute may be
      one reason why this class of compounds is effective in the oral delivery of
      heparin.

PMID- 11842413
TI  - Circular dichroism study of interactions of Fungizone or AmBisome forms of
      amphotericin B with human low density lipoproteins.
AB  - Amphotericin B (AmB), a potent antifungal agent used to treat invasive fungal
      infections, is still employed more than 40 years after its introduction in the
      pharmacopea. When injected into the blood stream, this antibiotic is carried by
      low density lipoproteins (LDLs) to which it induces the formation of oxidation
      products responsible in part for some of the severe adverse effects of the drug.
      However, the oxidative damages induced to LDLs are not yet understood. We present
      here the effects of the Fungizone and AmBisome forms of AmB on LDLs as compared
      to those of CuSO(4), a well-known powerful oxidant of LDLs. We use circular
      dichroism (CD) spectroscopy, which is particularly useful because it allows the
      investigation of the structural integrity of the proteic moiety of LDL upon
      interaction with AmB. The CD spectra also yield information on the drug itself
      because in its oligomer form it presents a strong dichroic signal in a spectral
      region different from that of the protein. Our results show that neither form of
      AmB changes the secondary structure of the protein while the helical content of
      the LDL is increased either in the presence of CuSO(4) alone or in the presence
      of CuSO(4) and AmBisome or Fungizone. On the other hand, the CD spectra of the
      antibiotic indicate that Fungizone AmB suffers important oxidative damage in the
      presence of LDLs and CuSO(4) while this damage is not present with AmBisome AmB.
      These observations lead us to propose that the structural modifications of the
      proteic part of LDLs induced by the Cu(2+) ions are involved in the important
      oxidative damage suffered by Fungizone AmB, which in this form is much more
      susceptible to interaction with its environment than AmBisome.

PMID- 11842414
TI  - Analysis of mebendazole polymorphs by Fourier transform IR spectrometry using
      chemometric methods.
AB  - A diffuse reflectance IR Fourier transform IR spectrometry (DRIFTS) method was
      developed for the rapid, direct measurement of mebendazole in drugs. Conventional
      KBr spectra and DRIFTS spectra were compared for the best determination of the
      active substance in the drug formulations. Two chemometric approaches were used
      in the data processing: multicomponent partial least squares (PLS2) and principal
      component regression. The best results were obtained with the PLS2 method.

PMID- 11842415
TI  - Spectroscopic studies and PM3 semiempirical calculations of Schiff bases of
      gossypol with L-amino acid methyl esters.
AB  - Three Schiff bases of racemic gossypol with L-amino acid methyl esters are
      synthesized and studied by FTIR and (1)H-NMR spectroscopy, and their structures
      are calculated by the PM3 semiempirical method. The Schiff bases in the study
      exist in the solid state and in solutions as enamine forms. The existence of
      diastereoisomers is very visible in the (1)H-NMR spectra. The amount of the
      diastereoisomers depends on the amount of time the solutions are rested in
      diffused light. The epimerization from D,L-isomer to L,L-isomer is very slow. The
      structures of the Schiff bases and the hydrogen bonds within these structures are
      discussed.

PMID- 11842416
TI  - Characterization of dioxygenated cobalt(II)-carnosine complexes by Raman and IR
      spectroscopy.
AB  - Raman and IR studies are carried out on carnosine (beta-alanyl-L-histidine,
      Carnos) and its complexes with cobalt(II) at different metal/ligand ratios and
      basic pH. Binuclear complexes that bind molecular oxygen are formed and
      information regarding the O-O bridge is obtained from the Raman spectra. When the
      Co(II)/Carnos ratio is <or=1, peroxobinuclear complexes are the predominant
      species and two forms (monobridged and dibridged) are identified by the presence
      of two Raman peaks in the nuO-O region (750-850 cm(-1)). These peroxo complexes
      can be oxidized to yield a superoxo complex when the metal slightly exceeds the
      Carnos concentration, and there are consequent shifts of the nuO-O band to higher
      wavenumbers. In addition, the chelated species in the 2 : 1 Co(II)/Carnos system
      is found to bind oxygen to a lesser degree. With respect to the coordination
      sites, each Co(II) ion of the binuclear dioxygenated complexes is bound to one
      oxygen atom and four nitrogen atoms: N(pi) and N(tau) of two Carnos molecules,
      the peptide, and the terminal amino nitrogen atoms. Conversely, when the
      metal/ligand ratio is 2, in addition to the dioxygenated complexes, a complex is
      formed in which the imidazole moiety of Carnos binds two different cobalt ions
      because the N(pi) and N(tau) nitrogens are both deprotonated.

PMID- 11842417
TI  - Foreword.

PMID- 11842418
TI  - Section I: Alphabetic list of terms with definitions.

PMID- 11842420
TI  - Section III: Abbreviations.

PMID- 11842419
TI  - Section II: Illustrations of selected waveforms.

PMID- 11842421
TI  - Molecular recognition: identifying compounds and their targets.
AB  - As a result of gene sequencing and proteomic efforts, thousands of new genes and
      proteins are now available as potential drug targets. The milieu of these
      proteins is complex and interactive; thousands of proteins activate, inhibit, and
      control each other's actions. The effect of blocking or activating a protein in a
      cell is far-reaching, and can affect whole, as well as adjacent pathways. This
      network of pathways is dynamic and a cellular response can change depending on
      the stimulus. In this section, the identification and role of individual proteins
      within the context of networked pathways, and the regulation of the activity of
      these proteins is discussed. Diverse chemical libraries, combinatorial libraries,
      natural products, as well as unnatural natural products that are derived from
      combinatorial biology (Chiu [2001] Proc. Natl. Acad. Sci. USA. 98:8548-8553),
      provide the chemical diversity in the search for new drugs to block new targets.
      Identifying new compounds that can become drugs is a long, expensive, and arduous
      task and potential targets must be carefully defined so as not to waste valuable
      resources. Equally important is the selection of compounds to be future drug
      candidates. Target selectivity in no way guarantees clinical efficacy, as the
      compound must meet pharmaceutical requirements, such as solubility, absorption,
      tissue distribution, and lack of toxicity. Thus matching biological diversity
      with chemical diversity involves something more than tight interactions, it
      involves interactions of the compounds with a variety host factors that can
      modulate its activity.

PMID- 11842423
TI  - Current practices in generation of small molecule new leads.
AB  - The current drug discovery processes in many pharmaceutical companies require
      large and growing collections of high quality lead structures for use in high
      throughput screening assays. Collections of small molecules with diverse
      structures and "drug-like" properties have, in the past, been acquired by several
      means: by archive of previous internal lead optimization efforts, by purchase
      from compound vendors, and by union of separate collections following company
      mergers. More recently, many drug discovery companies have established dedicated
      efforts to effect synthesis by internal and/or outsourcing efforts of targeted
      compound libraries for new lead generation. Although high
      throughput/combinatorial chemistry is an important component in the process of
      new lead generation, the selection of library designs for synthesis and the
      subsequent design of library members has evolved to a new level of challenge and
      importance. The potential benefits of screening multiple small molecule compound
      library designs against multiple biological targets offers substantial
      opportunity to discover new lead structures. Subsequent optimization of such
      compounds is often accelerated because of the structure-activity relationship
      (SAR) information encoded in these lead generation libraries. Lead optimization
      is often facilitated due to the ready applicability of high-throughput chemistry
      (HTC) methods for follow-up synthesis. Some of the strategies, trends, and
      critical issues central to the success of lead generation processes are discussed
      below.

PMID- 11842422
TI  - New technologies for chemical genetics.
AB  - Chemical genetics, in which small molecules are used in lieu of mutations to
      study biological processes, requires large and diverse chemical libraries to
      specifically perturb different biological pathways. Here we describe a suite of
      technologies that enable chemical libraries prepared by split-pool solid phase
      synthesis to be screened in a diverse range of chemical genetic assays. Compounds
      are synthesized on 500 micron high-capacity polystyrene beads, and arrayed into
      individual wells of 384-well plates using a hand-held bead arrayer. Compounds are
      cleaved from synthesis beads using a chemically-resistant ceramic dispensing
      system, producing individual stock solutions of single compounds. Nanoliter
      volumes of these solutions are then transferred into assay plates using an array
      of stainless steel pins mounted on a robotic arm. We have designed reusable 1536-
      and 6144-well assay plates made of silicone rubber that can be cast in the
      laboratory and filled by hand. This integrated technology platform enables
      hundreds of biological assays to be performed from the product of a single
      synthesis bead, enabling the results of different chemical genetic experiments to
      be directly compared.

PMID- 11842424
TI  - Life in the fast lane: high-throughput chemistry for lead generation and
      optimisation.
AB  - The pharmaceutical industry has come under increasing pressure due to regulatory
      restrictions on the marketing and pricing of drugs, competition, and the
      escalating costs of developing new drugs. These forces can be addressed by the
      identification of novel targets, reductions in the development time of new drugs,
      and increased productivity. Emphasis has been placed on identifying and
      validating new targets and on lead generation: the response from industry has
      been very evident in genomics and high throughput screening, where new
      technologies have been applied, usually coupled with a high degree of automation.
      The combination of numerous new potential biological targets and the ability to
      screen large numbers of compounds against many of these targets has generated the
      need for large diverse compound collections. To address this requirement, high
      throughput chemistry has become an integral part of the drug discovery process.

PMID- 11842425
TI  - Solid phase chemical technologies for combinatorial chemistry.
AB  - This article describes the exploration of synthetic methodologies on solid phase
      for combinatorial chemistry. Examples will cover various cyclisation strategies
      that include; the intramolecular Heck cyclisation leading to the formation of
      oxindoles, the radical cyclisation mechanism in the synthesis of furans, and a
      stereoselective cyclisation to form oxopiperazines.

PMID- 11842426
TI  - Applications of display technologies to proteomic analyses.
AB  - With the rapid accumulation of genetic information, development of general
      experimental approach suitable for large scale annotation and profiling of the
      whole proteome have become one of the major challenges in postgenomic era.
      Biomolecular display technologies, which allow expressing of a large pool of
      modularly coded biomolecules, are extremely useful for accessing and analyzing
      protein diversity and interaction profile on a large scale. Recent advances in
      protein display technologies and their applications to proteomic analyses have
      been discussed.

PMID- 11842427
TI  - Signal transduction driving technology driving signal transduction: factors in
      the design of targeted therapies.
AB  - A significant number of human diseases can be attributed to defects in cellular
      signal transduction pathways. Large-scale proteomics projects now in progress
      seek to better define critical components of signal transduction networks, to
      enable more intelligent design of therapeutic agents that can specifically
      correct disease-specific signaling alterations by targeting individual proteins.
      A complicating factor in this endeavor is the fact that intracellular signaling
      involves many diverse mechanisms that in sum finely modulate the activity of
      individual proteins in response to different biological inputs. Ability to
      develop reagents that selectively correct disease-associated signaling
      activities, while leaving intact benign or essential activities, encompassed
      within a single protein requires an intimate knowledge of pathway-specific
      control mechanisms. To illustrate these points, we provide examples of some of
      the complex control mechanisms regulating the Cas proteins, which contribute to
      integrin-dependent biological response. We then discuss issues involved in
      systematically incorporating information related to complex control mechanisms in
      proteomic databases. Finally, we describe some recent instances in which protein
      interaction technologies have been specifically adapted to identify small
      molecule agents that regulate protein response in physiologically desirable ways,
      and discuss issues relevant to future drug discovery efforts.

PMID- 11842428
TI  - Identifying and modifying protein-DNA and protein-protein interactions using a
      bacterial two-hybrid selection system.
AB  - A bacterial two-hybrid system based on transcriptional activation in E. coli has
      recently been described. A variety of different protein-DNA and protein-protein
      interactions from bacteria, yeast, and humans have been studied using this
      bacterial-based system. The method, because it is based in bacteria, offers
      significant advantages relative to its yeast counterpart including the ability to
      analyze complex libraries > 10(8) in size, ease of use, and speed. The ability to
      easily and rapidly process very large libraries make this system a powerful tool
      for identifying, modifying, or optimizing protein-DNA and protein-protein
      interactions.

PMID- 11842429
TI  - Computationally focusing the directed evolution of proteins.
AB  - Directed evolution has proven to be a successful strategy for the modification of
      enzyme properties. To date, the preferred experimental procedure has been to
      apply mutations or crossovers randomly throughout the gene. With the emergence of
      powerful computational methods, it has become possible to develop focused
      combinatorial searches, guided by computer algorithms. Here, we describe several
      computational methods that have emerged to aid the optimization of mutant
      libraries, the targeting of specific residues for mutagenesis, and the design of
      recombination experiments.

PMID- 11842430
TI  - Farnesylated proteins and cell cycle progression.
AB  - Post-translational modification of proteins by the addition of a farnesyl group
      is critical for the function of a number of proteins involved in signal
      transduction. Farnesylation facilitates their membrane association and also
      promotes protein-protein interaction. Recently, progress has been made in
      understanding the biological significance of farnesylation. First, effects of
      farnesyltransferase inhibitors (FTIs) on cancer cells have been examined using a
      variety of human cancer cells. This study showed that one of the major effects of
      FTIs is to alter cell cycle progression. Both G0/G1 enrichment and G2/M
      accumulation were observed depending on the cell line examined. Second, a number
      of novel farnesylated proteins have been characterized. Of these, Rheb and CENP
      E,F are of particular interest. Rheb, a novel member of the Ras superfamily G
      proteins, may play a role in the G1 phase of the cell cycle. CENP-E,F are
      centromere associated motors that play critical roles in mitosis. These results
      suggest important contributions of farnesylated proteins in the regulation of
      cell cycle progression.

PMID- 11842431
TI  - Resonance light scattering particles as ultrasensitive labels for detection of
      analytes in a wide range of applications.
AB  - We have developed a new detection technology that uses resonance light scattering
      (RLS) particles as labels for analyte detection in a wide range of formats
      including immuno and DNA probe type of assays in solution, solid phase, cells,
      and tissues. When a suspension of nano sized gold or silver particles is
      illuminated with a fine beam of white light, the scattered light has a clear (not
      cloudy) color that depends on composition and particle size. This scattered light
      can be used as the signal for ultrasensitive analyte detection. The advantages of
      gold particles as detection labels are that (a) their light producing power is
      equivalent to more than 500,000 fluorescein molecules, (b) they can be detected
      at concentrations as low as 10(-15) M in suspension by eye and a simple
      illuminator, (c) they do not photobleach, (d) individual particles can be seen in
      a simple student microscope with dark field illumination, (e) color of scattered
      light can be changed by changing particle size or composition for multicolor
      multiplexing, and (f) they can be conjugated with antibodies, DNA probes,
      ligands, and protein receptors for specific analyte detection. These advantages
      allow for ultra-sensitive analyte detection with easiness of use and simple and
      relatively inexpensive instrumentation. We have shown that our RLS technology can
      indeed be used for ultra-sensitive detection in a wide range of applications
      including immuno and DNA probe assays in solution and solid phases, detection of
      cell surface components and in situ hybridization in cells and tissues. Most of
      the assay formats described in this article can be adapted for drug fast
      throughput screening.

PMID- 11842432
TI  - Incorporating target heterogeneity in drug design.
AB  - Traditionally, structure-based drug design has been predicated on the idea of the
      lock-and-key hypothesis, i.e., the ideal drug should have a structure that
      complements the target site structurally and energetically. The implementation of
      this idea has lead to the development of drug molecules that are conformationally
      constrained and pre-shaped to the geometry of the selected target. The main
      drawback of this strategy is that conformationally constrained molecules cannot
      accommodate to variability in the target and, therefore, lose significant binding
      affinity even in the presence of small changes in the target site. There are
      three common situations that lead to binding site heterogeneity: (1) genetic
      diversity; (2) drug resistant mutations; and (3) binding site dynamics. The
      development of drugs that effectively deal with target heterogeneity requires the
      introduction of certain degree of flexibility. However, flexibility cannot be
      introduced indiscriminately because it would lead to a loss of binding affinity
      and specificity. Recently, structure-based thermodynamic strategies aimed at
      developing adaptative ligands that target heterogeneous sites have been proposed.
      In this article, these strategies are discussed within the context of the
      development of second generation HIV-1 protease inhibitors.

PMID- 11842433
TI  - High resolution, high-throughput amide deuterium exchange-mass spectrometry
      (DXMS) determination of protein binding site structure and dynamics: utility in
      pharmaceutical design.
AB  - Mass spectrometry-based peptide amide deuterium exchange techniques have proven
      to be increasingly powerful tools with which protein structure and function can
      be studied, and are unparalleled in their ability to probe sub-molecular protein
      dynamics. Despite this promise, the methodology has remained labor-intensive and
      time consuming, with substantial limitations in comprehensiveness (the extent to
      which target protein sequence is covered with measurable peptide fragments) and
      resolution (the degree to which exchange measurements can be ascribed to
      particular amides). I have developed and integrated a number of improvements to
      these methodologies into an automated high throughput, high resolution system
      termed Deuterium Exchange Mass Spectrometry (DXMS). With DXMS, complete sequence
      coverage and single-amide (amino acid) resolution are now rapidly accomplished.
      DXMS is designed to work well with large proteins and when only small amounts of
      material are available for study. Studies can be performed upon a receptor-ligand
      pair as they exist on or within a living cell (in vivo) without prior
      purification, allowing effective in situ study of integral membrane protein
      receptors. We have ambitious initiatives underway to make DXMS widely available
      both for basic academic research studies and commercial drug discovery efforts.
      In this paper I present an overview of DXMS technology and highlight some of the
      benefits it will provide in drug discovery and basic proteomics research.

PMID- 11842434
TI  - Object-oriented approach to drug design enabled by NMR SOLVE: first real-time
      structural tool for characterizing protein-ligand interactions.
AB  - As a result of genomics efforts, the number of protein drug targets is expected
      to increase by an order of magnitude. Functional genomics efforts are identifying
      these targets, while structural genomics efforts are determining structures for
      many of them. However, there is a significant gap in going from structural
      information for a protein target to a high affinity (K(d) < 100 nM) inhibitor,
      and the problem is multiplied by the sheer number of new targets now available.
      nature frequently designs proteins in classes that are related by the reuse,
      through gene duplication events, of cofactor binding domains. This reuse of
      functional domains is an efficient way to build related proteins in that it is
      object-oriented. There is a growing realization that the most efficient drug
      design strategies for attacking the mass of targets coming from genomics efforts
      will be systems-based approaches that attack groups of related proteins in
      parallel. We propose that the most effective drug design strategy will be one
      that parallels the object-oriented manner by which nature designed the gene
      families themselves. IOPE (Integrated Object-Oriented PharmacoEngineering) is
      such an approach. It is a three-step technology to build focused combinatorial
      libraries of potential inhibitors for major families and sub-families of enzymes,
      using cogent NMR data derived from representatives of these protein families. The
      NMR SOLVE (Structurally Oriented Library Valency Engineering) data used to design
      these libraries are gathered in days, and data can be obtained for large proteins
      (> 170 kDa). Furthermore, the process is fully object-oriented in that once a
      given bi-ligand is identified for a target, potency is retained if different
      cofactor mimics are swapped. This gives the drug design process maximum
      flexibility, allowing for the more facile transition from in vitro potency to in
      vivo efficacy.

PMID- 11842435
TI  - Computational method to assign microbial genes to pathways.
AB  - We present techniques that mine fully sequenced microbial genomes for functional
      relationships between genes. We show that genes related by one of four techniques
      are more likely to belong to the same cellular pathways. Furthermore, we
      demonstrate that the pathway of an uncharacterized gene may be inferred from
      those of its functionally related partners. Therefore, we are now able to assign
      most of the genes within bacteria to cellular pathways.

PMID- 11842436
TI  - Genomics approaches to drug discovery.
AB  - New approaches to drug discovery have come about in recent years as a result of
      important advances in genomics and bioinformatics. The availability of genome
      scale sequence data, the development of new tools for high-throughput gene
      expression monitoring, and improvements in the ability to analyze large data sets
      have revolutionized the field. In this article, we discuss three applications of
      genomics data in the drug discovery process: target discovery, prodrug
      strategies, and vaccine development.

PMID- 11842437
TI  - Feature extraction and normalization algorithms for high-density oligonucleotide
      gene expression array data.
AB  - Algorithms for performing feature extraction and normalization on high-density
      oligonucleotide gene expression arrays, have not been fully explored, and the
      impact these algorithms have on the downstream analysis is not well understood.
      Advances in such low-level analysis methods are essential to increase the
      sensitivity and specificity of detecting whether genes are present and/or
      differentially expressed. We have developed and implemented a number of
      algorithms for the analysis of expression array data in a software application,
      the DNA-Chip Analyzer (dChip). In this report, we describe the algorithms for
      feature extraction and normalization, and present validation data and comparison
      results with some of the algorithms currently in use.

PMID- 11842438
TI  - Revealing and utilizing receptor recognition mechanisms in a high-throughput
      world.
AB  - Recent genomic mapping promises to identify essentially all of the proteins that
      underpin normal and aberrant biology in humans. What genomics leaves undone is to
      determine how these proteins interact and integrate into molecular pathways in
      health and disease. Specific molecular interactions provide the fundamental
      mechanism for selectivity in virtually every aspect of biological structure and
      function. The convergence of structural and mutational studies makes it possible
      to define what parts of a protein are important for recognition. Still, knowing
      what is important does not necessarily foretell how binding epitopes actually
      function. We have applied the approach of epitope randomization on phage to
      explore how structural elements in such receptor recruitment systems as
      interleukin-5 (IL-5) and HIV-1 function in receptor recognition. This work has
      led in the IL-5 case to differentiation of recognition and activation epitopes,
      and this in turn has potential to help in the design of non-activating mimetics
      that could stimulate development of therapeutic antagonists for allergic
      inflammations such as asthma. Whether it is possible to differentiate recognition
      and activation in designing inhibitors in cases such as HIV-1 cell attachment and
      infection remains a tantalizing, but unsolved goal at present. Overall, these
      studies portray advances as well as limitations in the effort to decipher protein
      recognition mechanisms and utilize the wisdom gained for mechanism-based
      antagonist design in an increasingly high throughput world stimulated by the
      advent of genomics and proteomics.

PMID- 11842440
TI  - Reduced field response to perforant path stimulation after adrenalectomy: effect
      of nimodipine treatment.
AB  - Adrenalectomy enhances apoptosis in the rat dentate gyrus and concurrently
      decreases the field response of dentate cells to perforant path stimulation.
      Recent data showed that calcium current amplitude is increased 1 day prior to the
      appearance of apoptotic cells, pointing to calcium as a risk factor for the onset
      of apoptosis. We here tested if in vivo administration of nimodipine-thus
      presumably reducing dentate calcium influx through L type calcium channels
      prevents the appearance of apoptotic cells and the change in field responses
      after adrenalectomy. It was found that nimodipine does not largely alter the
      number of animals with apoptosis nor the average number of apoptotic cells in the
      tip of the suprapyramidal blade of the dentate gyrus. After nimodipine treatment,
      field responses in the dentate gyrus of adrenalectomized rats were comparable to
      responses in adrenally intact rats. However, this was due to a reduction of the
      field response in slices from adrenally intact rats, rather than a prevention of
      synaptic impairment in adrenalectomized rats. The data clearly indicates that in
      vivo nimodipine treatment is insufficient to prevent apoptosis and synaptic
      impairment after adrenalectomy.

PMID- 11842441
TI  - Enhancement of presynaptic performance in transgenic Drosophila overexpressing
      heat shock protein Hsp70.
AB  - Prior heat shock confers protection to Drosophila synapses during subsequent heat
      stress by stabilizing quantal size and reducing the decline of quantal emission
      at individual synaptic boutons. The major heat shock protein Hsp70, which is
      strongly induced by high temperatures in Drosophila, may be responsible for this
      synaptic protection. To test this hypothesis, we investigated synaptic protection
      and stabilization at larval neuromuscular junctions of transgenic Drosophila
      which produce more than the normal amount of Hsp70 in response to heat shock.
      Overexpression of Hsp70 coincides with enhanced protection of presynaptic
      performance, assayed by measuring mean quantal content and percentage success of
      transmission. Quantal size was not selectively altered, indicating no effects of
      overexpression on postsynaptic performance. Thus, presynaptic mechanisms can be
      protected by manipulating levels of Hsp70, which would provide stability to
      neural circuits otherwise susceptible to heat stress.

PMID- 11842442
TI  - Time window of autoreceptor-mediated inhibition of limbic and striatal dopamine
      release.
AB  - Forebrain dopamine release is under the local control of D2 family (D2 and D3)
      autoreceptors. In this study, autoreceptor-mediated modulation of forebrain
      dopamine release was investigated using amperometry in brain slices following
      local electrical stimulation. 350 microm-thick slices of nucleus accumbens or
      dorsolateral neostriatum were prepared from male Wistar rats (150-200 g) and
      superfused with artificial cerebrospinal fluid at 32 degrees C. Dopamine release
      was evoked by electrical pulses (0.1 ms, 10 mA) across bipolar tungsten
      stimulating electrodes and measured at carbon fibre microelectrodes using fixed
      potential amperometry (+300 mV vs. Ag/AgCl). Peak dopamine release on stimulation
      (single pulse) was 0.75 microM (neostriatum) and 1.37 microM (nucleus accumbens).
      Metoclopramide (1 microM) had no significant effect on DA efflux from a single
      pulse in either region. Using paired pulse stimuli, dopamine release on the
      second pulse varied according to the interval between the two pulses. At very
      long intervals (>20 sec), dopamine release was similar to that for the first
      pulse. At shorter intervals, dopamine efflux was attenuated. Metoclopramide had
      no effect on second pulse dopamine release when the pulse was applied at short
      (<0.1 sec) or long (>5.0 sec) intervals after the first. At intermediate
      intervals, metoclopramide significantly increased second pulse dopamine release.
      The peak dopamine autoreceptor effect occurred at approximately 550 ms in
      neostriatum and approximately 700 ms in nucleus accumbens. The onset time is due
      both to diffusion of dopamine from the release sites to the autoreceptors and
      receptor-effector mechanisms. These findings may have implications for the local
      control of forebrain dopamine function in physiological and pathological states.

PMID- 11842443
TI  - Alleviation of motor hyperactivity and neurochemical deficits by endocannabinoid
      uptake inhibition in a rat model of Huntington's disease.
AB  - Recent studies have demonstrated a loss of cannabinoid CB1 receptors in the
      postmortem basal ganglia of patients affected by Huntington's disease (HD) and in
      transgenic mouse models for this disease. These studies have led to the notion
      that substances that increase the endocannabinoid activity, such as receptor
      agonists or inhibitors of endocannabinoid uptake and/or metabolism, might be
      useful in the treatment of hyperkinetic symptoms of this disease. In the present
      study, we employed a rat model of HD generated by bilateral intrastriatal
      injections of 3-nitropropionic acid (3-NP), a toxin that selectively damages
      striatal GABAergic efferent neurons. These rats exhibited biphasic motor
      disturbances, with an early (1-2 weeks) hyperactivity followed by a late (3-4
      weeks) motor depression. Analysis of GABA, dopamine, and their related enzymes,
      glutamic acid decarboxylase and tyrosine hydroxylase, in the basal ganglia proved
      marked decreases compatible with the motor hyperkinesia. In addition, mRNA levels
      for CB1 receptor, neuronal-specific enolase, proenkephalin, and substance P
      decreased in the caudate-putamen of 3-NP-injected rats. There were also
      reductions in CB1 receptor binding in the caudate putamen, the globus pallidus,
      and, to a lesser extent, the substantia nigra. By contrast, mRNA levels for
      tyrosine hydroxylase in the substantia nigra remained unaffected. Interestingly,
      the administration of AM404, an inhibitor of endocannabinoid uptake, to 3-NP
      injected rats attenuated motor disturbances observed in the early phase of
      hyperactivity. Administration of AM404 also tended to induce recovery from the
      neurochemical deficits caused by the toxin in GABA and dopamine indices in the
      basal ganglia. In summary, morphological, behavioral, and biochemical changes
      observed in rats intrastriatally lesioned with 3-NP acid were compatible with a
      profound degeneration of striatal efferent GABAergic neurons, similar to that
      occurring in the brain of HD patients. As expected, a loss of CB1 receptors was
      evident in the basal ganglia of these rats. However, the administration of
      substances that increase endocannabinoid activity, by inhibiting the uptake
      process, allowed an activation of the remaining population of CB1 receptors,
      resulting in a significant improvement of motor disturbances and neurochemical
      deficits. These observations might be relevant to the treatment of hyperkinetic
      symptoms in HD, a human disorder with unsatisfactory symptomatic treatment for
      most patients.

PMID- 11842444
TI  - Inhibition of glutamate release by fluspirilene in cerebrocortical nerve
      terminals (synaptosomes).
AB  - Fluspirilene, a neuroleptic drug which is used clinically to treat schizophrenic
      patients, is a dopamine D2 receptor antagonist. Besides its well-known actions on
      the dopamine receptors, fluspirilene also displays calcium channel-blocking
      activity. The aim of this study was to investigate the effect of fluspirilene on
      the 4-aminopyridine (4AP)-evoked glutamate release in the cerebrocortical nerve
      terminals (synaptosomes). Fluspirilene reduced 4AP-evoked glutamate release in a
      concentration-dependent manner. This inhibitory effect was associated with a
      decrease in the depolarization-evoked increase in the cytoplasmic free Ca2+
      concentration ([Ca2+]C), which could be completely abolished by the Ca2+ channel
      blocker omega-CgTX GVIA. Furthermore, fluspirilene did not produce any effect on
      ionomycin-evoked glutamate release. These results suggest that fluspirilene
      inhibits glutamate release primarily by reducing presynaptic Ca2+ influx via N
      type Ca2+ channels in rat cerebrocortical nerve terminals. This finding implies
      that presynaptic Ca2+ channel blockade concomitant with inhibition of glutamate
      release and possibly other neurotransmitters release may contribute to the
      antischizophrenic action of fluspirilene.

PMID- 11842445
TI  - Demonstration of competition between endogenous dopamine and [11C]raclopride
      binding in in vitro brain slices using a dynamic autoradiography technique.
AB  - To elucidate the mechanism of in vivo binding competition between radioligand and
      endogenously released transmitter, we examined the influence of depolarization
      induced dopamine (DA) release on [11C]raclopride-specific binding to D2 receptors
      in slices of living brain tissues using dynamic positron autoradiography. Rat
      brain slices were incubated in a chamber with [11C]raclopride in oxygenated
      medium at 34 degrees C for 150 min. Two-dimensional images of radioactivity in
      the slices were recorded on a storage phosphor screen and dynamic changes were
      measured. When the brain slices were exposed to the depolarization agents (25 mM
      K+, 50 mM K+, and 20 microM veratridine), the percentage inhibition of striatal
      [11C]raclopride-specific binding was 22 +/- 4%, 44 +/- 8% and 54 +/- 7% of the
      control, respectively. The percentage inhibition of [11C]raclopride-specific
      binding during each depolarization treatment agreed proportionally with the
      amount of DA released into the medium. However, preexposure of brain slices to
      the same depolarization treatment (50 mM K+) did not affect the [11C]raclopride
      specific binding, suggesting that the reduction in receptor density and/or
      affinity was not involved in the decrease of [11C]raclopride-specific binding.
      [11C]Raclopride-specific binding decreased dose-dependently in the presence of
      exogenously added DA (range 0.005-3mM). The synaptic DA concentration during each
      depolarization treatment estimated using three different methods. These results
      suggest that the decrease of [11C]raclopride-specific binding to striatal slices
      following evoked DA release is due to competition between endogenous DA and
      raclopride. It is unlikely that changes in D(2) receptor density or in affinity
      of the receptors for raclopride are involved. These results provide supportive
      evidence for in vivo binding competition between radioligand and endogenous
      neurotransmitter.

PMID- 11842448
TI  - Issues involved in the accrual of respondents.

PMID- 11842446
TI  - Altered prolactin response to M-chlorophenylpiperazine in monkeys previously
      treated with 3,4-methylenedioxymethamphetamine (MDMA) or fenfluramine.
AB  - 3,4-Methylenedioxymethamphetamine ("Ecstasy," MDMA) and fenfluramine, widely used
      by humans, are potent brain serotonin (5-HT) neurotoxins in animals. Thus, there
      is concern that humans previously exposed to these amphetamine derivatives may
      have incurred brain 5-HT neurotoxicity. However, assessing the status of brain 5
      HT neurons in the living organism is challenging. To determine whether MDMA-
      and/or fenfluramine-induced 5-HT neurotoxicity can be detected during life using
      neuroendocrine methods, groups of monkeys previously treated with neurotoxic
      regimens of MDMA or fenfluramine, along with saline-treated controls, underwent
      neuroendocrine challenge with the direct 5-HT agonist and 5-HT-releasing drug, m
      chlorophenylpiperazine (m-CPP). Animals treated 2 weeks previously with MDMA
      exhibited a nonsignificant reduction in the prolactin response to m-CPP. In
      contrast, monkeys treated 3 1/2 years previously with MDMA or 2 years previously
      with fenfluramine exhibited significantly increased prolactin responses to m-CPP.
      No significant differences in cortisol concentrations were noted between groups
      at any time point. These data indicate that neuroendocrine challenge with m-CPP
      is capable of detecting substituted amphetamine-induced 5-HT neurotoxicity in
      living primates, but that the recency of drug exposure is an important
      consideration. Changes in the neuroendocrine response to m-CPP over time in
      animals with substituted amphetamine-induced neurotoxicity may be related to
      aberrant 5-HT reinnervation of the basal forebrain that occurs over time in
      monkeys previously treated with neurotoxic doses of MDMA or fenfluramine.

PMID- 11842447
TI  - Anesthesia affects the disposition of [18F]fluoro-A-85380: a PET study in
      monkeys.

PMID- 11842450
TI  - Advancing the quality of oncology nursing care: Interlink Community Cancer
      Nurses' model for reflective practice.
AB  - Since 1996, Interlink Community Cancer Nurses have been using reflective practice
      as a team to share knowledge and experience amongst peers. The use of reflective
      practice enables the nurse to examine decision-making in patient situations and
      uncover the knowledge and artistry that is embedded in nursing practice. This
      article describes how reflection is practised by specialist cancer nurses to
      advance the quality of caregiving. The use of a structured framework for
      reflection which incorporates ways of knowing in nursing is an essential feature
      of the Interlink model for reflection. The development of a process for
      reflection within the Interlink program has at times been challenging. However,
      the Interlink nurses' experience with reflection is believed to be critical to
      the ongoing development of the program and the individual nurse. Interlink nurses
      have found that guided reflection, the creation of an environmental milieu for
      reflection and personal knowing, and self-evaluation are critical to the process
      of becoming a self-reflective practitioner.

PMID- 11842449
TI  - Effects of an educational intervention on the anxiety of women awaiting
      mastectomies.
AB  - The purpose of this experimental study was to assess the effects of an
      individualized psychocognitive educational intervention on preoperative anxiety
      in women awaiting mastectomies. A total of 60 women aged between 27 and 65 years
      were randomly distributed to two groups of 30 participants. Using the Situational
      Anxiety Inventory (IAS) along with repeated-measures variance analysis, it was
      noted that, immediately following the educational interventions (both
      experimental and control) there was a significant reduction (p < 0.01) of anxiety
      with the experimental group having an additional reduction of 4.83 (p = 0.05).
      The day before surgery, only the experimental educational intervention resulted
      in a significant reduction (p = 0.03) of anxiety, but the difference between the
      two educational interventions was not significant. These results appear to
      support Lazarus and Folkman's stress, appraisal and coping theory which states
      that direct action on cognitive perception can influence a feeling of threat as
      assessed through the level of anxiety.

PMID- 11842452
TI  - A country of contrasts.

PMID- 11842451
TI  - The impact and management of cancer-related fatigue on patients and families.
AB  - Fatigue has been identified as both a chronic and recurrent problem for
      individuals diagnosed with and treated for cancer, yet there is little
      information on how to manage the impact of fatigue. Describing what happens to
      individuals and their families as a result of fatigue and identifying what
      individuals do to manage or reduce the impact of fatigue are essential elements
      in determining multidimensional nursing interventions. The purpose of this pilot
      study was to examine the impact of fatigue on individuals with cancer of the lung
      and their families, and explore how they managed as a result of the fatigue. A
      semi-structured interview guide was used with 22 lung cancer patients and 14
      family members six weeks post completion of radiation therapy. Results indicated
      that fatigue was not reported as a major concern by many of the participants in
      this study. For those who did experience fatigue, it was considered an
      inconvenience and a frustration that had to be dealt with for a limited time
      period. Some patients appeared to gradually adjust and accommodate to the fatigue
      and were not really aware of the changes that took place over time. Over half of
      the family members felt more of the impact of fatigue than did their loved ones.
      Family subtly assumed or took over responsibilities and activities the patient
      could no longer perform. The symptom of fatigue has been well documented in the
      cancer experience as both a chronic and recurrent problem for individuals
      diagnosed with and treated for cancer. The emphasis of previous work has been on
      deriving a conceptual definition of fatigue, achieving consensus on a definition,
      and developing theoretical frameworks to guide further study of this complex
      construct. Fatigue has been conceptualized as a multidimensional phenomenon,
      attributable to multiple causes and having a negative effect on quality of life
      (Piper, 1993; Tiesinga, Dasson, & Halfens, 1996). Describing what happens to
      individuals and their families as a result of fatigue and identifying what
      individuals do to manage or reduce the effects caused by the fatigue are
      essential elements in determining multidimensional nursing interventions.

PMID- 11842453
TI  - Nursing's role in shaping cancer control for the future: the Canadian Strategy
      for Cancer Control.

PMID- 11842454
TI  - Report from ONS 2001: the Oncology Nursing Society 26th Annual Congress, May 17
      20, 2001, San Diego, California.

PMID- 11842455
TI  - Was the House of Lords right to dismiss Mrs Pretty's appeal?

PMID- 11842456
TI  - The answer to reducing patient violence towards NHS staff.

PMID- 11842457
TI  - No automatic disclosure to patients of healthcare staff HIV status.

PMID- 11842458
TI  - Nurse who disclosed to the press details about a celebrity patient.

PMID- 11842460
TI  - Urinary tract stones: causes, complications and treatment.
AB  - Stones or calculi in the urinary tract affect up to 12% of men and 5% of women by
      the age of 70 years, with more than a third of individuals having a strong family
      history (Unwin, 1996). Complications include obstruction in the urinary tract,
      pain, nausea, vomiting and sepsis. Common causes are: urine stasis, infection,
      presence of foreign bodies, dehydration, diet and periods of immobility.
      Encouraging initial diuresis could exacerbate rather than relieve symptoms.
      Discharge advice is a key feature of preventing recurrence once the predisposing
      factors have been identified. The relationship between patient and nurse is an
      invaluable and ideal opportunity for nurses to educate patients in appropriately
      changing dietary habit and in maintaining a urine output of greater than 2 litres
      per day.

PMID- 11842461
TI  - Emergency nurse practitioners: should the role be developed?
AB  - Trusts have to face a number of challenges in the provision of accident and
      emergency (A&E) services. One suggested way forward is to introduce the emergency
      nurse practitioner (ENP) role into A&E. However, this is not without controversy.
      Thus, this review has been undertaken in order to identify and assess any
      available evidence. A total of nine studies met the inclusion criteria. The
      studies fell into a number of categories, e.g. overall evaluation of the role,
      the use of radiography, and patient satisfaction. Several studies monitored
      transit times though A&E and there was some limited cost-benefit analysis.
      Overall, there was little difference found between the performance of ENPs in
      comparison with that of senior house officers (SHOs). The studies available for
      review are of poor quality, which limits the conclusions that can be made. At
      best, it would be reasonable to state that there is no evidence to demonstrate
      that ENPs are better or worse than SHOs in seeing, treating and discharging
      patients with minor injuries in A&E.

PMID- 11842459
TI  - Acceptability of early discharge with drain in situ after breast surgery.
AB  - The aim of this study was to evaluate a policy of early discharge at 48 hours
      with suction drains in situ in a cohort of patients undergoing surgery for breast
      cancer and to compare this with a similar cohort of patients discharged 5 days
      postoperatively. This was an integrated qualitative/quantitative study using a
      questionnaire given to both groups providing comparable results by using averages
      and percentages to describe and synthesize the data. A questionnaire of open and
      closed questions was given to 19 patients who chose to be discharged at 48 hours
      with drains in situ, and 16 patients who opted to be discharged at 5 days after
      drain removal. The study demonstrated that patients regarded early discharge as
      being safe and were satisfied with their care when they were given a high level
      of support from hospital and community staff. The results also identified that it
      was important for patients to make their own decision about either early
      discharge or standard discharge in order to be satisfied with the outcome of
      their care.

PMID- 11842462
TI  - Introducing a professional doctorate in nursing and midwifery.
AB  - The convergence of a number of factors has led to the emergence of what has come
      to be known as the 'professional doctorate'. This new doctoral education diverges
      from the model of research doctorates that have historically predominated for
      more than a century. The background to these changes and the impetus for the
      development of this relatively new approach to doctoral preparation is outlined
      in this article. The infancy of the professional doctorate means little empirical
      data exist about their operation or their success. In this light, the development
      of an evaluative framework is described in relation to the implementation of a
      new professional doctorate for nurses and midwives that has been introduced at
      the University of Sheffield.

PMID- 11842463
TI  - Legal aspects of consent 18: issues relating to euthanasia.

PMID- 11842464
TI  - Reflection: possible strategies to improve its use by qualified staff.
AB  - Reflection is now a prerequisite for all nurses, midwives and health visitors
      (UKCC, 2001). It is the method endorsed by the UKCC to promote the development of
      informed, knowledgeable and safe practice, and qualified practitioners are
      required to maintain a personal professional profile containing evidence of
      reflection on practice. The aim of this article is to examine why qualified
      practitioners may be reluctant to reflect formally, to speculate on the possible
      barriers to reflection, and to suggest how reflection can be promoted positively
      as an integral part of nursing practice. The article begins with an examination
      of definitions of reflection, reflective theory and the purpose of reflection,
      and continues by questioning whether the concept of reflection has been embraced
      as eagerly by nurses at 'grass roots' as it has by academia, the nursing press
      and the UKCC. It is suggested that several barriers to effective reflection may
      create a division between practitioners and the professional hierarchy regarding
      the conceived common practice of reflection, and strategies are proposed that may
      help to overcome these barriers. The discussion concludes by prioritizing the
      need for a clear definition and concept analysis of reflection, supported by long
      term investment into research that explores the effect of reflection on clinical
      practice and patient care.

PMID- 11842466
TI  - Ward sister/charge nurse: the key role in nursing.

PMID- 11842465
TI  - Oasis: an innovative alternative dressing for chronic wounds.
AB  - Chronic wounds in patients with multiple systemic factors present a significant
      clinical challenge for clinicians. Oasis Wound Dressing is derived from porcine
      small intestine which, when placed in a non-infected wound, stimulates new tissue
      and an absorbable, natural template for the growth of new tissue. Emerging
      evidence suggests that it is beneficial for patients with chronic, non-healing
      wounds complicated by multiple systemic factors.

PMID- 11842467
TI  - The use of honey in the treatment of infected wounds: case studies.
AB  - Honey is gaining popularity as a dressing for chronic wounds. Existing literature
      attributes honey with a number of useful properties, such as a broad-spectrum
      antimicrobial activity, deodorization, debriding and anti-inflammatory actions
      and stimulation of new tissue growth. Case studies are being published
      increasingly which record positive outcomes with its use. Recent national media
      attention has featured the beneficial effects of honey in wound care and patients
      are beginning to request treatment. While honey may become a useful and widely
      accepted product for wound management in the future, the following case studies
      demonstrate that not all the expected beneficial effects are always realized in
      practice.

PMID- 11842468
TI  - Evaluating pressure-reducing foam mattresses and electric bed frames.
AB  - It could be argued that pressure ulcer prevention is simply a matter of matching
      those patients at risk of developing tissue damage with suitable pressure
      reducing equipment. However, as many authors have identified, this can be
      complicated because of the lack of reliable evidence to support many products.
      This article seeks to evaluate the combination of a pressure-reducing mattress
      with an electric profiling bed frame. The study was conducted in a high
      dependency cardiac surgery unit. Forty-four subjects were recruited during a 6
      month period and their progress observed. Two outcome measures were used:
      pressure ulcer incidence and perceptions of comfort. No pressure ulcers developed
      during the trial and the perceptions of comfort were generally positive. The
      small sample size restricts the conclusions that can be drawn from the study, but
      when taken in conjunction with other small studies in this area there appear to
      be benefits from using such a combination of equipment.

PMID- 11842469
TI  - Tissue viability nurses must have  a united front.

PMID- 11842470
TI  - Assessment and management of pain in fungating wounds.
AB  - Pain is a complex phenomenon that affects individuals in different ways. Wound
      pain is often seen as an inevitable consequence of wound care and many patients
      may suffer from chronic wound pain. One group of patients that presents a
      challenge in wound pain management are those with fungating malignant wounds. The
      effective management of wound pain may be compromised by inappropriate or non
      existent pain assessment, the inefficient prescribing of analgesia, and confusion
      about the appropriate use of dressing products to reduce wound pain. Many
      healthcare professionals lack knowledge about pain and pain control and hold
      inappropriate beliefs and attitudes about analgesic medications, in particular
      relating to opioid drugs. This article aims to address these issues by providing
      a brief overview of pain physiology followed by strategies for pain assessment
      and options for the management of pain related to fungating wounds, including
      pharmacological treatments, wound care techniques and complementary therapies.

PMID- 11842471
TI  - The current status of maggot therapy in wound healing.
AB  - The clinical use of sterile maggots under the brand name LarveE has increased
      steadily in the UK since they were introduced in the UK in late 1995. Some 50
      articles have been published in the last 4 years that describe the cost
      effectiveness of maggot therapy in a variety of wound types including leg ulcers,
      pressure ulcers and diabetic ulcers. The ability of these creatures to combat
      wound infection has been well documented including those caused by antibiotic
      resistant strains of bacteria such as methicillin-resistant Staphylococcus
      aureus. No significant risks or adverse events have been linked to the use of
      maggots, although their presence may increase pain levels in leg ulcers
      associated with ischaemic disease.

PMID- 11842473
TI  - Compliance with science: benefits of developing community leg clubs.
AB  - As a district nurse providing leg ulcer management in a rural community, the
      author was aware that the effectiveness of compression therapy was, in many
      cases, compromised by poor compliance to treatment. Once the author had
      researched the underlying causes of non-compliance, she addressed the issues by
      developing innovative leg ulcer clinics ('Leg Clubs') to provide holistic care in
      an environment of patient empowerment, destigmatization and peer support.
      Analysis of data acquired over an 11-month period illustrates that this new
      approach has yielded significant reductions in the incidence of non-compliance,
      allowing the benefits of compression therapy to be realized.

PMID- 11842472
TI  - Developing an equipment library: the solution to increasing demand.
AB  - Within the clinical practice arena there appears to be an increasing reliance on
      the use of dynamic pressure-relieving mattress systems to prevent and treat
      pressure damage. This has increased the financial burden for many trusts despite
      the efficacy and effectiveness of such products being largely unknown. Cullum et
      al (2000) suggest that studies that evaluate specific products or types of
      products to prevent or cure pressure ulcers are limited in size and quality. This
      article describes the experiences of an acute NHS trust in managing the
      increasing demand for pressure-relieving equipment. By setting up an equipment
      library, resources have been effectively managed, traditional cultures regarding
      ownership of equipment have been challenged, and financial benefits have been
      demonstrated.

PMID- 11842474
TI  - Mental health nursing in 2001: what happens next?

PMID- 11842475
TI  - Can models of post-traumatic stress disorder contribute to the application of
      cognitive therapy by nurse therapists when dealing with individuals affected by
      the Omagh bombing? An overview.
AB  - As mental health professionals practising in an evolving multidisciplinary trauma
      and recovery team in Omagh, Northern Ireland, the by now infamous Omagh bombing
      of 15 August 1998 brought abruptly to attention the potential for adverse
      psychological consequences resulting from exposure to such trauma. As nurse
      therapists, this event provoked interest in the entity of post-traumatic stress
      disorder (PTSD) as being one of the possible negative psychological consequences,
      and the relevance and application of cognitive theory and practice in its
      treatment. Whilst recognizing that there is no single cognitive theory or model
      of anxiety disorder, this paper focuses on the approach of Beck and allied
      approaches when referring to cognitive theory and practice. It is intended to
      proffer a broad overview of areas the authors consider relevant in order to
      develop an appreciation of the entity of PTSD, and its evolution, having given a
      synopsis of the event that provoked interest. Finally, acknowledgement and a
      brief explication of some of the theoretical models of PTSD to date will be made,
      and the relevance and application of cognitive theory and principals in the
      treatment of the disorder will be considered.

PMID- 11842477
TI  - Legal and ethical aspects of seclusion: an Australian perspective.
AB  - The debate about the appropriateness of seclusion as a nursing practice in
      inpatient settings in the 21st century continues, with powerful and often emotive
      arguments from those who view it as an anachronistic and punitive form of ward
      management, and from others who see it as a useful emergency measure to protect
      individuals from imminent harm. This is the first paper, however, to focus on
      legal and ethical issues in relation to the use of seclusion, with policies and
      practices in Australian psychiatric institutions viewed within the context of
      worldwide trends. The interplay of ethical principles and international mental
      health law has encouraged a move towards the provision of care and treatment of
      the disturbed psychiatric patient within the least restrictive environment,
      supposedly reducing the potential for the inappropriate use of control
      mechanisms. Nevertheless, current legislation can be seen to preserve the status
      quo because it legitimizes seclusion as an acceptable nursing practice, albeit
      within given parameters, thereby defusing the imperative to promote the reduction
      and abolition of psychiatric control mechanisms and seek new possibilities in
      mental health care.

PMID- 11842476
TI  - An initial exploration of community mental health nurses' attitudes to and
      experience of sexuality-related issues in their work with people experiencing
      mental health problems.
AB  - Human sexuality is a complex dynamic concept that escapes simple definition.
      Within nursing there seems to be a preference for broad holistic definitions that
      emphasize sexuality as an aspect of the unique human character. Whilst the
      nursing literature mostly portrays sexuality as wholesome and good, it also notes
      that sexuality can be a vehicle for the expression of power, hostility or hatred.
      In this study, the authors did not prescribe or limit the definition of
      'sexuality'. Rather the term 'sexuality' was used in a broad sense in order to
      embrace the range of variables within the concept and allow respondents to
      consider the issues according to their own perspective. Despite broad acceptance
      of sexuality as a legitimate focus of health care, clinicians remain ambivalent
      about actively broaching sexual issues and there is a potential for clients'
      needs to go unmet. A number of intertwining variables can influence sexuality
      related nursing practice. Nurses' attitudes are regarded as major barriers that
      prevent open discussion on the topic. This study aims to explore a sample of
      community mental health nurses' views on the topic of sexuality in relation to
      their work with clients. The authors adapted a sexual ideology scale previously
      used for the purposes of teaching students and promoting discussion. The
      questionnaire was distributed to nurse delegates at an annual CPNA conference.
      Two of the authors were available throughout the conference to discuss the study.
      Delegates were asked to recruit CMHN colleagues following the conference in order
      to increase the sample. The data are described and analysed using SPSS for
      Windows. Respondent characteristics have been cross-tabulated with item responses
      and analysed using chi-square and other statistical tests of association. The
      respondents (n = 122) confirmed sexuality as a relevant clinical issue and there
      was an overwhelming affirmation of people with mental health problems as sexual
      beings. Sixty-three per cent (n = 77) of respondents anticipated that people with
      mental health problems who are in relationships might experience sexual problems,
      and 52.4% (n = 64) agreed that a sexual history should be routinely included in
      assessment. Seventeen per cent (n = 21) had encountered clients becoming sexually
      aroused during the administration of a depot injection in the community. The
      authors identify this as an area of concern that warrants further investigation.
      The results indicate that although awareness of sexuality issues may be high
      there may be less agreement as to how such awareness should translate into CMHN
      practice.

PMID- 11842478
TI  - Comprehensive nursing education in Victoria: rhetoric or reality?
AB  - Significant and widespread changes to the education of the psychiatric nursing
      workforce in Victoria, Australia are resulting in serious problems in the
      recruitment of new nursing staff. In reviewing the available literature, it is
      evident that undergraduate nursing students do not commence their educational
      program with a strong interest in pursuing a career in psychiatric nursing. In
      light of this knowledge, the role of education in providing a comprehensive view
      of the nursing profession becomes paramount. Research investigating the impact of
      education on the attitudes of students to psychiatric nursing as a career option
      has produced mixed and often inconclusive results. A longitudinal study was
      undertaken in Victoria, Australia. Students of the majority of universities in
      which undergraduate nursing programs were operating participated in this study.
      The participants were asked to rank nine areas of nursing specialty in order of
      preference at the commencement and immediately prior to the completion of the
      nursing program. Despite a significant improvement in the popularity of
      psychiatric nursing as a career choice, this area was ranked at number 8 at both
      pre- and post-program test. The analysis of open-ended questions demonstrated a
      marked change in the overall attitudes towards the mentally ill and psychiatric
      nursing.

PMID- 11842479
TI  - Fiction, poetry and mental health: expressive and therapeutic uses of literature.
AB  - People with experience as mental health clients, mental health nurses, writers
      and other professionals have used literature to benefit mental health service
      users in various ways. These include expressive writing, as well as applications
      in psychotherapy and counselling and to deal with specific problems and symptoms.
      In addition, therapeutic story-telling, bibliotherapy and poetry therapy have
      been used. Various benefits have been described, but some accounts do not include
      evidence of clinical effectiveness. However, positive treatment outcomes have
      been reported in research papers and other literature, with particular evidence
      of clinical effectiveness in some studies of bibliotherapy, therapeutic writing
      and poetry therapy. Further work is needed to clarify and measure the
      effectiveness of various expressive and therapeutic uses of literature. The
      authors also recommend collaboration among practitioners and the need for
      supporting evidence for proposals for increased resources in this field.

PMID- 11842480
TI  - Primary nursing: staff perception of changes in ward atmosphere and role.

PMID- 11842481
TI  - A systematic review of the effects of interprofessional education on staff
      involved in the care of adults with mental health problems.
AB  - Interprofessional education (IPE) is commonly advocated in policy documentation
      as a means of enhancing collaboration between heath and social care staff.
      However, little is known about the effects of this type of education. This paper
      reports findings from a systematic review which was commissioned to search and
      begin assessing the quality of the published evidence relating to the effects of
      IPE on staff involved in the care of adults with mental health problems. Results
      from this study indicate that there is a current lack of rigorous evidence into
      the effects of IPE in this field. Conclusions from this work are made in
      connection to mental health policy and recommendations are offered for
      strengthening the evaluation of IPE.

PMID- 11842482
TI  - Absconding of patients from an independent UK psychiatric hospital: a 3-year
      retrospective analysis of events and characteristics of absconders.
AB  - The need for accurate local information on the scale, nature and outcome of
      absconding or Absence Without Leave (AWOL) from an independent UK psychiatric
      hospital led to this 3-year (1997-1999) retrospective analysis of of AWOL data.
      One hundred and forty-eight AWOL incidents involving 88 patients were identified.
      Absconders were found to be significantly younger, more likely to be detained
      upon admission and more likely to be unmarried than a control group (n = 1378) of
      non-absconders. There were no significant differences for sex, length of
      admission or ethnicity. Descriptive data on the circumstances surrounding AWOL
      events are given, with at least 24 (16.2%) incidents having serious adverse
      outcomes. Baseline absconding rates are presented for the specialist clinical
      divisions within the hospital. There is a need for more detailed studies of
      absconding by patients within the Adolescent Mental Health Service subgroup where
      the absconding rate was relatively high and engagement in risk activity whilst
      AWOL relatively frequent.

PMID- 11842484
TI  - New agents and future directions in biotherapy.
AB  - Many new biotherapy agents to treat cancer are being studied as single agents and
      in combination with conventional cancer therapy, such as chemotherapy. These
      agents include the monoclonal antibodies, rituximab, trastuzumab, alemtuzumab,
      and IMC-C225. Radioimmunotherapy, a type of biotherapy that combines a
      radioactive isotope with a monoclonal antibody, also is being studied and has
      shown promise in the treatment of lymphoma. A tyrosine kinase inhibitor, STI 571,
      has been approved recently by the U.S. Food and Drug Administration. Several
      vaccines as cancer treatment are currently under investigation. Other biotherapy
      agents being investigated include angiogenesis inhibitors, such as endostatin,
      antivascular endothelial cell growth factor, and thalidomide, an agent that
      inhibits the formation of blood vessels that supply tumors.

PMID- 11842483
TI  - Rasburicase: an innovative new treatment for hyperuricemia associated with tumor
      lysis syndrome.
AB  - Rasburicase is a new treatment for hyperuricemia, a metabolic manifestation of
      tumor lysis syndrome (TLS). Rasburicase has a unique mechanism of action that
      allows uric acid byproducts to be easily excreted in the urine. Clinical trials
      have shown that rasburicase has a rapid onset of action that allows chemotherapy
      to be delivered on time and prevents hyperuricemia-related complications,
      including renal compromise. The drug has been used successfully in adults and
      children. The main side effect of rasburicase is the potential for a
      hypersensitivity reaction. The drug is contraindicated in patients with glucose 6
      phosphate dehydrogenase (G6PD) deficiency because this can precipitate hemolytic
      anemia. The drug has not been studied in patients with a history of allergies or
      asthma. Oncology nurses play a major role in the assessment and management of TLS
      related complications. They must assess patients for G6PD deficiency and signs
      and symptoms of hypersensitivity reaction before and during chemotherapy or other
      therapeutic interventions. Nurses play a direct role in preventing complications
      related to TLS and contributing to the quality of life in this patient
      population.

PMID- 11842486
TI  - The ABCs of low blood cell count.
AB  - Children with cancer often receive treatment that may include both chemotherapy
      and radiation. These agents primarily can affect the body's hematopoietic system.
      The authors designed a teaching poster, in both English and Spanish, to assist in
      teaching the key concepts of low blood cell counts to pediatric patients and
      their families. Having a child with cancer often is an overwhelming experience,
      and most parents and family members need to learn new information in a variety of
      ways to maximize their understanding and retention. This poster was not designed
      to be a substitute for patient-family teaching but, rather, to serve as a
      reinforcement tool.

PMID- 11842485
TI  - Revisiting the road not taken: integrating palliative care into oncology nursing.

PMID- 11842487
TI  - Deep vein thrombosis in the patient with cancer.
AB  - The association between thromboembolic disease and cancer has long been
      recognized. Armand Trousseau first brought this association to the attention of
      the medical profession in 1868 (Haire, 2000). Oncology nurses need to be
      knowledgeable about preventive measures, early signs and symptoms of
      thromboembolic disease, and complications of therapy.

PMID- 11842488
TI  - Painful lesions in a pancytopenic patient.

PMID- 11842489
TI  - Addressing patients' end-of-life needs: the role of the oncology nurse.

PMID- 11842490
TI  - Massage therapy for patients with cancer.
AB  - Patients with cancer often use massage therapy as an adjunct treatment. Oncology
      nurses can be advocates for patients seeking massage therapy by educating them to
      be informed consumers of massage therapy. They can stress that patients with
      cancer use massage therapists who have graduated from accredited programs, meet
      state licensure requirements, and have specialized training in the massage of
      patients with cancer. Oncology nurses often are the link between the physician
      ordering or approving this therapy and the LMT delivering the therapy. LMT's need
      information about a patient's cancer diagnosis, comorbidities, type of treatment,
      and reponse to treatment to safely provide massage therapy. Nurses play an
      important role in conveying this information and information LMT's about any
      special considerations, such as the presence of neutropenia or thrombocytopenia.
      Safe and effective massage therapy to patients with cancer only is achieved when
      the patient, healthcare providers, and LMT collaborate effectively.

PMID- 11842491
TI  - Herpes zoster. Treating postherpetic neuralgia.

PMID- 11842492
TI  - Liposomal doxorubicin.

PMID- 11842494
TI  - End of life care: symptom management.

PMID- 11842493
TI  - Smoking withdrawal and prolonged hospitalization.
AB  - Many individuals who smoke are hospitalized for extended periods of time for
      treatment of their diseases. These patients are at increased risk for developing
      withdrawal symptoms and maladaptive behavior because hospitals have adopted smoke
      free policies in accordance with federal law and consumer pressures. Tobacco
      addiction often is overlooked by healthcare providers or receives low priority on
      admission. Oncology nurses care for a chronic population of people who often
      require lengthy treatments and frequent complications resulting in admissions to
      the hospital. Nurses need to identify high-risk patients; continually educate
      themselves, their patients, and their patients' families about smoking withdrawal
      and cessation therapies; anticipate coping difficulties; and be prepared to
      manage inappropriate behavior when necessary. A multidisciplinary team approach
      using consistent reinforcement and support offers the best patient outcomes while
      maximizing safety.

PMID- 11842495
TI  - End of life care: ethical issues.
AB  - Nurses spend more time with patients who are facing the end-of-life than any
      other member of the health care team. Yet, studies have shown that many nurses
      feel inadequately prepared to provide the comprehensive care so important at the
      end-of-life. Penny Marshall, RN, PhD nursing professor at Johnson County
      Community College has recently attended a three-day course on end-of-life care
      held in Pasadena, CA. The American Associate of Colleges of Nursing (AACN) and
      the City of Hope (COH) National Medical Center received a 3 1/2 year grant from
      the Robert Wood Johnson Foundation to conduct this training program for
      undergraduate nursing school faculty members (Geraldine Bednash, PhD, FAAN and
      Betty R. Ferrell, PhD, FAAN, Principal Investigators). The training program,
      entitled End-of-Life Nursing Education Consortium (ELNEC), was conducted by
      distinguished faculty of researchers, educators, authors, and leaders in the
      field of palliative care; and aimed to provide faculty with comprehensive
      information on end-of-life care and resources to integrate into nursing school
      programs. The following two articles draw on this extensive curriculum to discuss
      two important aspects of end-of-life care: 1) common ethical dilemmas and complex
      questions that arise in the practice setting; and 2) symptom management during
      palliative care.

PMID- 11842497
TI  - Stages of grief. Fact or fiction?

PMID- 11842496
TI  - Nursing education: advocating for the dying.

PMID- 11842498
TI  - Health care: the engine that drives economic recovery?

PMID- 11842499
TI  - Smith: consolidating Catholic and community health systems benefits the
      community.

PMID- 11842500
TI  - Leading IDSs heed the call to invest in IT.
AB  - Case studies of 11 leading integrated delivery systems (IDSs) found all of these
      organizations are committed to investing in the development of sophisticated IT
      systems. The case-study IDSs' primary concerns regarding IT investments were
      related to achieving adequate financial and patient care returns, accessing
      capital, finding qualified IT staff, finding reliable IT vendors, achieving
      physician acceptance, and sharing software and IT solutions with other IDSs.
      Among the competitive advantages these IDSs have gained from advanced IT
      capabilities are improved patient satisfaction due to superior service outcomes
      and the IDS's ability to access clinical information from any point within its
      delivery system, reduced prescription errors and adverse drug reactions, enhanced
      quality-improvement efforts, reduced costs associated with telephone calls and
      paper processing, and enhanced ability to recruit clinical personnel.

PMID- 11842503
TI  - Business associates: a HIPAA compliance challenge.
AB  - The final rule implementing the privacy standards mandated by the Health
      Insurance Portability and Accountability Act (HIPAA) of 1996 imposes substantial
      requirements on covered entities with respect to their business associates--those
      parties providing certain services to, or on behalf of, the covered entities. A
      covered entity must develop a contract with each of its business associates that
      sets forth the conditions under which the business associate may use or disclose
      the protected health information it receives from the covered entity. The
      contract also must delineate the covered entity's obligations with respect to the
      business associate, which include ensuring individuals' access to their protected
      health information and taking certain steps to respond to a breach of the privacy
      standards by the business associate. The business associate requirements do not
      apply to the covered entity's workforce, disclosures to providers for treatment
      purposes, certain financial transactions, certain jointly administered government
      programs, and, provided that certain other restrictions are met, disclosures made
      by group health plans to plan sponsors.

PMID- 11842502
TI  - The HIPAA privacy rule: practical advice for academic and research institutions.
AB  - The Final Standards for Privacy of Individually Identifiable Health Information
      (privacy rule) of the Health Insurance Portability and Accountability Act (HIPAA)
      of 1996 holds particular importance for academic and research organizations
      because they use patient information in the provision of experimental healthcare
      services. In developing a strategy to comply with the final privacy rule, these
      organizations require an understanding of certain standards that hold
      significance for them. Specifically, organizations should establish patient
      privacy guidelines for non-employee researchers the organization should consider
      partners in business with whom the organization should share its researcher
      guidelines. These organizations also should understand the difference between
      consent and authorization, how requirements of the final privacy rule build upon
      those of the Federal Policy for the Protection of Human Subjects, and the
      differing roles of privacy boards and institutional review boards.

PMID- 11842501
TI  - Projecting the budget impacts of HIPAA.
AB  - Although the Health Insurance Portability and Accountability Act (HIPAA) of 1996
      was meant to simplify and reduce the cost of delivering health care, the initial
      steps to comply with all areas of the law are projected to be very costly.
      Healthcare organizations should take the time to figure the cost of HIPAA
      compliance into their budgets to avoid costly surprises as compliance measures
      are implemented. There are several steps a healthcare finance manager can take to
      manage budget expectations for HIPAA compliance.

PMID- 11842504
TI  - AICPA allows low-cost options for compiled financial statements.
AB  - The AICPA Accounting and Review Services Committee's (ARSC) SSARS No. 8,
      Amendment to Statement on Standards for Accounting and Review Services No. 1,
      Compilation and Review of Financial Statements, issued in October 2000, allows
      financial managers to provide plain-paper, compiled financial statements for the
      exclusive use of management. Such financial statements were disallowed in 1979
      when the AICPA issued SSARS No. 1, Compilation and Review of Financial
      Statements. With the issuance of SSARS No. 8, financial managers can prepare
      plain-paper, compiled financial statements when third parties are not expected to
      rely on the financial statements, management acknowledges such restrictions in
      writing, and management acknowledges its primary responsibility for the adequacy
      of the financial statements.

PMID- 11842505
TI  - Cost analysis can help a group practice increase revenues.
AB  - Undertaking a cost analysis to determine the cost of providing specific services
      can help group practices negotiate increased payment and identify areas for cost
      reduction. An OB/GYN practice in Pennsylvania undertook a cost analysis using the
      resource-based relative value system. Using data from the cost analysis, the
      practice was able to negotiate increased payment for some of its services. The
      practice also was able to target some of its fixed costs for reduction. Another
      result of the analysis was that the practice was able to focus marketing efforts
      on some of its most profitable, elective services, thereby increasing revenues.
      In addition, the practice was able to reduce the provision of unprofitable
      services.

PMID- 11842506
TI  - Healthcare providers face bumpy transition to 2002 outpatient PPS rates.

PMID- 11842507
TI  - 15 essential steps of IT project management.

PMID- 11842508
TI  - Evaluating a defined-contribution employee pension plan.

PMID- 11842509
TI  - Improving employer/employee commitment.

PMID- 11842510
TI  - One impressive analyst.

PMID- 11842511
TI  - Latex allergy & dermatitis.

PMID- 11842512
TI  - Feet first.

PMID- 11842513
TI  - Critical elements for effective ergonomics.

PMID- 11842514
TI  - Environmental design for the older worker.

PMID- 11842515
TI  - Taking motivation and recognition online.

PMID- 11842516
TI  - The hidden hazard of protective apparel.

PMID- 11842517
TI  - What do the new form 300 regulations mean to you?

PMID- 11842518
TI  - 2002 outlook: caution prevails.

PMID- 11842519
TI  - Driven to distraction.

PMID- 11842520
TI  - Protecting against Bacillus anthracis.

PMID- 11842521
TI  - Knowledge management for EHS professionals.

PMID- 11842522
TI  - IAQ hazards in commercial buildings.

PMID- 11842523
TI  - Breaking the mold.

PMID- 11842524
TI  - Behavior genetic research on gambling and problem gambling: a preliminary meta
      analysis of available data.
AB  - A meta-analysis of family and twin studies on gambling and problem gambling was
      initiated in an effort to determine the probable role of genetic factors in high
      risk wagering. Two twin studies and 17 investigations employing the family
      history or family study method were included in this meta-analysis. A summation
      of the 19 studies produced a small but significant overall effect size (weighted
      phi = .10, unweighted phi = .13), with both family (weighted phi = .12,
      unweighted phi = .14) and twin (weighted phi = .06, unweighted phi = .05) studies
      achieving significant individual mean effects. Given the paucity of twin data,
      further analysis was confined to family studies and revealed a stronger familial
      effect for the sons of problem gambling fathers than for the daughters of problem
      gambling mothers and for more severe forms of problem gambling than for less
      severe forms of problem wagering, and was strongest for high severity problem
      gambling in males. The implications of these results are discussed.

PMID- 11842525
TI  - A comparison of gambling by Minnesota public school students in 1992, 1995, and
      1998.
AB  - The purpose of this study was to compare rates of gambling among Minnesota public
      school students between 1992, 1995, and 1998. The three samples included 75,806
      students in the 9th and 12th grades in 1992; 73,897 9th and 12th grade students
      in 1995; and 78,564 9th and 12th grade students in 1998. Students were
      administered the Minnesota Student Survey, a 121-item, anonymous, self
      administered, paper-and-pencil questionnaire that inquires about multiple
      behavioral domains, including gambling behaviors. The same questionnaire, with
      minor revisions to the gambling items, was administered in 1992, 1995, and 1998
      to students in their classrooms by the Minnesota Department of Education. The
      results showed two opposite trends. On the one hand, fewer students gambled in
      1998 than in 1995 and 1992. On the other hand, there was a small, but growing
      number of 12th grade students who gambled frequently. In terms of trends over
      time for specific games, the lottery showed a significant decline in the number
      of 9th grade students who played at all. There was also a significant increase in
      the number of 12th grade students who played the lottery weekly or more often.
      The findings that frequent lottery gambling has increased among 12th grade
      students and that underage gambling continues among these students, are both
      cause for concern. This is the first generation of youth to be exposed to
      widespread accessability to legalized gambling venues and gambling advertising.
      Legalized gambling may be a new "rite of passage" for some of today's youth. It
      will be important to continue to monitor youth gambling and to provide
      information and resources to assist youth in making healthy decisions about their
      gambling behavior.

PMID- 11842526
TI  - Manipulations of the features of standard video lottery terminal (VLT) games:
      effects in pathological and non-pathological gamblers.
AB  - The present study was conducted to identify game parameters that would reduce the
      risk of abuse of video lottery terminals (VLTs) by pathological gamblers, while
      exerting minimal effects on the behavior of non-pathological gamblers. Three
      manipulations of standard VLT game features were explored. Participants were
      exposed to: a counter which displayed a running total of money spent; a VLT
      spinning reels game where participants could no longer "stop" the reels by
      touching the screen; and sensory feature manipulations. In control conditions,
      participants were exposed to standard settings for either a spinning reels or a
      video poker game. Dependent variables were self-ratings of reactions to each set
      of parameters. A set of 2(3) x 2 x 2 (game manipulation [experimental
      condition(s) vs. control condition] x game [spinning reels vs. video poker] x
      gambler status [pathological vs. non-pathological]) repeated measures ANOVAs were
      conducted on all dependent variables. The findings suggest that the sensory
      manipulations (i.e., fast speed/sound or slow speed/no sound manipulations)
      produced the most robust reaction differences. Before advocating harm reduction
      policies such as lowering sensory features of VLT games to reduce potential harm
      to pathological gamblers, it is important to replicate findings in a more
      naturalistic setting, such as a real bar.

PMID- 11842528
TI  - Through a narrow window. Opportunities to attract real prospects can be slim.

PMID- 11842529
TI  - A well of wishes. Residents' dreams come true with help from the community.

PMID- 11842527
TI  - What makes gambling news?
AB  - This paper examines print media coverage of casino and electronic gambling in one
      Canadian province from 1992 to 1997. It provides a theme analysis of content of
      234 gambling stories printed in the top two daily newspapers in Nova Scotia. The
      findings of our content analysis indicate that pro-gambling corporate and
      political newspaper sources waged a successful media campaign and constructed a
      powerful public rhetoric in support of new gambling products, services, and
      institutions. The media, for their part, gave visibility and form to these
      structured messages. They helped create expectations about gambling and economics
      and gambling and government. Law and order, and moral and medical discourses
      about gambling, we discovered, were minor representations in the news coverage,
      although moral narratives were a pervasive secondary theme in much of the
      reporting. At bottom, the press produced a "politics of truth" about gambling
      that was both an external exercise of power and an internal organizational
      production.

PMID- 11842530
TI  - LTC confidential. How--and why--to get a customer's-eye view of your facility.

PMID- 11842531
TI  - HIPAA and the death of silos. A model for the insurance industry to follow.

PMID- 11842533
TI  - [Chronological and regional differences of testicular cancer--epidemiological
      analysis of incidence in gunma prefecture and estimated data of national survey,
      and of death in Japan].
AB  - PURPOSE: The incidence of testicular cancer is rare. However, it is a significant
      cancer in that it develops not only in old age but also in children and younger
      age. We investigated the epidemiological characteristics of testicular cancer in
      Japan, in order to elucidate its features and problems. PATIENTS AND METHODS: We
      surveyed hospitals and clinics in and around Gunma prefecture that treated
      patients with urologic diseases and reviewed the pathology records from 1985 to
      1994, and calculated the annual age-adjusted incidence rates of testicular
      cancer. Incidence rates in Japan were taken from the estimates made by 'The
      Research Group for Population-based Cancer Registration in Japan'. The annual
      number of deaths, annual age-adjusted death rates from 1947 and 1998, the age
      specific death rates and decrease rate of them, and the prefectural standardized
      mortality ratio (SMR) from 1973 and 1998 was calculated from the data reported by
      Ohno et al. and statistical tables kept in 'Statistics and Information
      Department, Minister's Secretariat, Ministry of Health and Welfare'. RESULTS: In
      Gunma Prefecture, the annual age-adjusted incidence rates tended to increase. In
      estimated data of national survey, it slightly increased from 1975-79 to 1980-84,
      and remained stable thereafter. The annual number of deaths and age-adjusted
      death rates tended to decrease from around 1980. The peak of age-specific death
      rates was seen in infants, age 20 to 40 and old age. The decrease in the age
      specific death rate was prominent for age under 20 and old age, but not
      significant for age 25 to 34. Prefectures in which SMR was high (> or = 120) were
      distributed all over Japan, but prefectures in which SMR was low (< or = 80) were
      concentrated in western Japan. CONCLUSIONS: The annual number of deaths and age
      adjusted death rates began to decrease from around 1980, which coincided with the
      time the clinical trial of cis-platinum began. More than 100 deaths of testicular
      cancer are reported even now, early diagnosis, early treatment, and improvement
      of treatment strategy to far-advanced cases are necessary.

PMID- 11842532
TI  - Alternatives for Alzheimer's. Three basic approaches offer help and hope.

PMID- 11842534
TI  - [Management of enterovesical fistula in patients with Crohn's disease].
AB  - PURPOSE: Enterovesical fistula in patients with Crohn's disease is intractable.
      Although there are some reports that the enterovesical fistula were successfully
      treated conservatively, closure of the fistula cannot always be achieved and
      surgical intervention may required for those patients. Since surgical closure of
      entero-entero fistula has a high risk of relapse, the strategy for treating
      enterovesical fistula has not been established. We evaluated the clinical
      findings especially in management of enterovesical fistula in Crohn's disease.
      PATIENTS AND METHODS: Two hundred two patients (mean age was 28.4 year old, range
      12-69; 152 men and 50 women) were diagnosed as Crohn's disease during a period of
      15 years between 1986 and 2000 in our institute. The incidence and the clinical
      results regarding the diagnosis and the treatment of enterovesical fistula in
      these patients were retrospectively evaluated. RESULTS: Seven in 202 patients
      were diagnosed to have an enterovesical fistula (3.5%, 6 men and 1 woman). The
      period from the initial diagnosis of Crohn's disease to the recognition of the
      enterovesical fistula was 11 to 204 months (mean 92.1 months). Enterovesical
      fistula was revealed and/or visualized by radiological enterography in 6,
      cystography in 2, cystoscopy in 6, and CT in 4 patients. Surgical interventions
      were finally conducted in all 7 patients after the failure of conservative
      treatment for 10 to 146 days (mean 68.2 days). Surgical procedures performed for
      closing the enterovesical fistula were partial cystectomy with fistulectomy in 5,
      fistulectomy with bladder wall overlay-suture in 2, and bladder wall overlay
      suture alone in 1. No relapse of enterovesical fistula was recognized in any
      patient in the average observation of 41.6 months. CONCLUSION: Although the
      treatment of Crohn's disease has been advanced, enterovesical fistula is shown to
      be resistant to conservative treatment options and it makes patients in
      unfavorable status for relatively long duration. Our evaluation shown here
      demonstrated the sufficient surgical results on the closure of enterovesical
      fistula without any relapse, and was different from the high relapse rate after
      the surgical management of entero-entero fistula in similar observation period.
      Surgical interventions of enterovesical fistula caused by Crohn's disease might
      have an advantage to make diseased patients improved in shorter duration.

PMID- 11842535
TI  - [Transition zone index in predicting therapeutic efficacy of benign prostatic
      hyperplasia].
AB  - PURPOSE: We studied how transition zone index (TZ index) influenced the
      therapeutic efficacy of benign prostatic hyperplasia (BPH). In addition, we
      retrospectively investigated the availability of TZ index in selection of the
      more effective therapeutic method for BPH. METHOD: One hundred twenty-five
      patients with symptomatic BPH whose prostate volume (PV) was more than 15 ml by
      transrectal ultrasonography were investigated. Sixty-nine men underwent
      transurethral resection of the prostate (TURP) whereas 56 were treated with alpha
      1-blocker. Tamsulosin hydrochloride. These patients were evaluated based on TZ
      index as well as ordinary parameters of BPH; international prostatic symptom
      score, QOL score, peak flow rate and PV. RESULTS: The patients with TZ index > or
      = 0.5 showed good therapeutic results in the TURP group. On the other hand, the
      patients with TZ index < 0.5 showed favorable response in alpha 1-blocker group.
      Multivariate analysis revealed that TZ index affected the therapeutic efficacy
      more strongly than the other parameters. CONCLUSION: TZ index had strong
      influence on therapeutic efficacy of TURP or alpha 1-blocker and seemed to be a
      useful tool for the selection of BPH therapy.

PMID- 11842536
TI  - [Experience of nephroureterectomy with modified "pluck" method--En bloc removal
      of kidney and ureter].
AB  - PURPOSE: Transurethral removal of the ureter in nephroureterectomy has been
      reported by several centers as being a useful procedure. We also have employed
      this procedure in selective cases, but we had several problems in this procedure.
      So we tried the modified pluck nephroureterectomy technique (En bloc removal of
      kidney and ureter) to improve the procedure. MATERIALS AND METHODS: Since October
      1999 to September 2000, we employed this technique in 9 cases with renal pelvic
      or ureteral tumor, 2 with renal cell carcinoma and 3 with benign diseases.
      Standard nephrectomy is performed. After transurethral resection of the ureteral
      meatus, the distal ureter is freed by blind retroperitoneal dissection and
      plucked out of the bladder in continuity with the kidney. The bladder is
      drainaged for 6-10 days after surgery. RESULTS: The average time and blood loss
      during the operation were 247 minutes and 287 ml. No appreciable complications
      such as retroperitoneal urine leakage or hemorrhage during or after the procedure
      were observed. CONCLUSIONS: The modified pluck technique is useful because of its
      easiness and minimal invasiveness.

PMID- 11842537
TI  - [Upregulation of costimulatory adhesion molecule (CD80) in rat kidney with
      ischemia/reperfusion injury].
AB  - PURPOSE: Ischemia/reperfusion injury associated with organ transplantation
      affects early graft function and acute rejection. Recently, it has been suggested
      that ischemic insult increases the immunogenicity of the organ. The purpose of
      this study was to determine the expression of a cell adhesion molecule, CD80,
      which plays an important role in the costimulatory pathway for full T-cell
      activation in organ transplantation. MATERIALS AND METHODS: Wistar male rats
      weighing 150-180 g were divided into control group and ischemia groups with
      temporary clamping of the left renal artery for 30, 60 and 180 minutes. The left
      kidneys obtained at 1 hour, 1, 3, 7 and 14 days after reperfusion were subjected
      to total RNA extraction followed by reverse transcriptase-PCR (RT-PCR),
      fluorescence immunostaining and histological staining. RESULT: The expression of
      CD80 by RT-PCR was not observed in the control group, but was observed in the
      ischemia groups from 1 to 14 days after reperfusion. Fluorescence immunostaining
      of CD80 was positive in the ischemia groups, but not in the control group. CD80
      expression was detected mainly in the endothelium of the glomeruli and the
      peritubular vessels. CONCLUSION: These results indicate that CD80 is upregulated
      by ischemic insult, and that the costimulatory pathway may be enhanced by
      ischemia/reperfusion injury without alloantigens.

PMID- 11842539
TI  - [Toxic shock syndrome due to methicillin resistant staphylococcus aureus (MRSA)
      after total prostatectomy].
AB  - A 55-year-old man with prostate cancer received a total prostatectomy. Two days
      after the operation, he suffered from high fever and shaking chilliness, followed
      by skin eruption, hypotension, diarrhea and chest pain. The results of blood
      bacterial culture and endotoxin were negative. Toxic shock syndrome was
      suspected, and the administration of vancomycin (VCM) and continuous hemodialysis
      filtration (CHDF) were performed. The steroid pulse therapy for adult respiratory
      distress syndrome (ARDS) and the treatments for DIC were also done, and they were
      effective. The desquamation of the extremity was observed on 10 days after the
      operation. MRSA was finally identified from pus discharge of the operation wound
      13 days after the operation. The prevention and treatments for toxic shock
      syndrome were discussed.

PMID- 11842538
TI  - [Management of pregnancy and delivery after augmentation cystoplasty].
AB  - We report 2 cases of women who became pregnant and experienced vaginal delivery
      after augmentation cystoplasty. CASE 1: A 23-year-old woman with spina bifida
      became pregnant 3 years after augmentation sigmoidocystoplasty which had been
      performed to treat intractable urinary tract infection and urinary incontinence.
      During pregnancy, she developed febrile urinary tract infection twice which
      required antibiotics together with tight adherence to clean intermittent
      catheterization. At 36 weeks of gestation, she was safely delivered of a healthy
      baby. No deterioration of urinary continence level and renal function was
      observed after the delivery. CASE 2: A 32-year-old woman became pregnant 23 years
      after augmentation ileocecocystoplasty which had been performed to reconstruct
      diverted urinary tract due to a congenital hour-glass bladder. At 19 weeks of
      gestation, she developed acute pyelonephritis and hydronephrosis at right kidney
      which required antibiotics and indwelling urethral catheter. At 21 weeks of
      gestation, a drip infusion of ritodrine hydrochloride was started and maintained
      until 34 weeks of gestation to inhibit premature uterine contraction. At 29 weeks
      of gestation, she developed acute pyelonephritis and progressive hydronephrosis
      at left kidney, for which percutaneous nephrostomy drainage was deemed to be
      mandatory. She was delivered of a healthy baby at 36 weeks of gestation. Ten days
      after the delivery, both nephrostomy tube and indwelling urethral catheter were
      removed and clean intermittent catheterization was resumed. Total renal function
      was maintained during and after the pregnancy, and no deterioration of urinary
      continence was observed after the delivery. Since urinary tract infection is
      extremely common during pregnancy after augmentation cystoplasty, prevention and
      prompt intervention for urinary tract infection should be mandatory. Significant
      upper tract obstruction, if developed, should be treated by an effective urinary
      drainage. Thus, urological as well as obstetrical appropriate management is
      mandatory for the safe accomplishment of pregnancy and delivery after
      augmentation cystoplasty.

PMID- 11842540
TI  - [Rapidly growing renal angiomyolipoma during pregnancy with tumor thrombus into
      the inferior vena cava: a case report].
AB  - A case of renal angiomyolipoma rapidly growing during pregnancy with tumor
      thrombus into the inferior vena cava is reported. Angiomyolipoma in a 31-year-old
      woman was incidentally found by ultrasonography. CT scan revealed a fat
      containing tumor in the right kidney with 4 cm in diameter. The patient was
      followed at outpatient clinic without any treatment. Fifteen months later, the
      post-delivery follow-up CT scan showed that tumor size had grown up to 11 cm in
      diameter. Although laparoscopic right nephrectomy was tried, open transperitoneal
      right nephrectomy was performed because the tumor thrombus extending into the
      inferior vena cava was found during the laparoscopic procedure. Pathological
      diagnosis was angiomyolipoma of the kidney. There are several reports that
      indicate angiomyolipoma grows rapidly during pregnancy. Our case demonstrates
      that careful follow-up is required for angiomyolipoma in women with possible
      conception and delivery.

PMID- 11842541
TI  - [Phyllodes tumor of the prostate: a case report].
AB  - Prostatic phyllodes tumor is an unusual lesion for which there are only
      occasional reports in the literature. We encountered a phyllodes tumor of the
      prostate in a 36-year-old man who had complained of urinary frequency and dysuria
      for one month. In October 1998, he visited our hospital and had a transurethral
      resection of the prostate (TUR-P) for obstructive symptoms. He experienced
      recurrent same symptoms in September 1999 and underwent another TUR-P. The
      pathologic examination at this time revealed phyllodes tumor. In the tumor,
      despite its regular alternating growth of ducts and stroma, the stromal element
      appeared histologically malignant, showing marked atypia and rhabdomyosarcoma
      like components. Consequently, in December 1999, the patient underwent radical
      prostatectomy with lymph node dissection. The resection margins and pelvic lymph
      nodes were free of tumor. The patient remains alive and well after 14 months.

PMID- 11842542
TI  - [A case of transitional cell carcinoma of the bladder with active urinary tract
      tuberculosis].
AB  - A 63-year-old man was admitted to our hospital complaining of painful urination.
      Urinalysis demonstrated pyuria and microscopic hematuria. Cystoscopy revealed the
      bladder tumor and the reddish mucosa. Transurethral biopsy was performed and the
      pathological examination showed transitional cell carcinoma in the bladder tumor
      and epithelioid granuloma in the reddish mucosa. Acid-fast bacilli smeas of urine
      sample and urine culture of Mycobacterium tuberculosis were positive. Therefore
      the treatment of urinary tuberculosis was started and the patient received intra
      arterial chemotherapy combined with radiation. After the therapy, radical
      cystectomy and bilateral cutaneous ureterostomies were performed. Pathological
      study revealed transitional cell carcinoma and epithelioid granuloma in the
      removed bladder. The reports of urinary epithelial carcinoma with urinary tract
      tuberculosis were rare and, including our case, the 10 cases in Japanese
      literature are reviewed.

PMID- 11842543
TI  - [Sling suspension of incontinent urinary reservoir].
AB  - We report a case and surgical technique of successful sling suspension of
      insufficient efferent limb of continent urinary reservoir, which has occurred
      urinary incontinence. A 64-year-old male, who received radical cystectomy with
      continent urinary reservoir, had been suffered urinary incontinence from the
      reservoir about one year after surgery. Various procedures, such as the repair of
      the efferent limb of the reservoir, addition of the ileal patch, instillation of
      scopolamine, oxybutynin into the reservoir and an injection of GAX collagen in
      the efferent limb, were not effective for his urinary incontinence. Finally, anti
      incontinence procedure of sling at an efferent limb using abdominal rectus muscle
      fascia was employed and obtained a continence for 2 years after operation. The
      principle of this surgery is same with that of sling suspension for female stress
      incontinence. It is advisable for the incontinent urinary reservoir when it has
      an enough length of efferent limb.

PMID- 11842544
TI  - [The use of predeposited autologous blood transfusion for radical prostatectomy].
AB  - PURPOSE: In reference to the cases in which radical prostatectomy was performed
      after storage of autologous blood, we retrospectively study the usefulness of
      this procedure and proper amount of blood stored. PATIENTS AND METHODS: The
      subjects included 62 cases in which radical prostatectomy was performed after
      storage of autologous blood from October, 1997 to March, 2000. As the amount of
      blood to be stored, either 800 ml or 1,200 ml was selected optionally as the
      amount of blood to be stored, and blood was stored at a rate of 400 ml once a
      week. Erythropoietin, 24,000 units was injected subcutaneously after storage of
      blood, and an iron preparation 200 mg/day was administered orally throughout the
      period. RESULTS: Homologous blood transfusion could be avoided in 58 out of 62
      cases, the avoidance rate being 93.5%. With 200 ml of autologous blood as 1 unit,
      104 units out of 330 units were discarded, the disposal rate being 31.5%. To
      lower the disposal rate, we studied whether there is any parameter that can
      predict the loss of blood preoperatively. As a result, we found a significant
      difference in the loss of blood between the body mass index of less than 24 and
      that of more than 24. Blood storage and transfusion produced no side-effects.
      CONCLUSION: Storing autologous blood in radical prostatectomy is considered
      useful since homologous blood transfusion can be avoided at a high percentage and
      no side-effects are produced. The body mass index is useful for predicting the
      loss of blood and determining a proper amount of blood to be stored.

PMID- 11842545
TI  - [Coronary artery bypass grafting in the patients with renal dysfunction].
AB  - We studied coronary artery bypass grafting (CABG) in patients with renal
      dysfunction. From April 1994 to October 1999, 59 patients with renal dysfunction
      underwent CABG. The patients were divided into 2 groups: group A: 18 patients
      with end stage renal disease who were receiving hemodialysis, group B; 41
      patients with creatinine levels higher than 1.5 mg/dl who were not supported by
      dialysis. We compared and analyzed the findings of there 2 groups. Regarding
      preoperative factors, the incidence of old myocardial infarctions, diabetes
      mellitus and old cerebral infarctions did not differ significantly between the 2
      groups. Regarding perioperative factors, the incidence of the number of vessel
      diseases, emergency operations, operation times and blood transfusions did not
      differ significantly between the 2 groups. Regarding the post-operative course,
      the hospital mortality rates demonstrated low levels in 2 groups. The graft
      patency of group A was 95%, while it was 99% in group B. The post-operative in
      hospital days was 24.8 days in the group A, while it was 30.1 days in the group
      B. No significant difference was observed between the 2 groups. As a results,
      post-operative hemodialysis was needed in 8 of the patients who underwent on-pump
      CABG from group A. The actual survival rates were 75.3% in group A and 84.3% in
      group B at 4 years. The cardiac event free rate for group A was 93.3%, while it
      was 97.5% in group B at 4 years. In conclusion, CABG may improve the post
      operative outcome in renal dysfunction patients. In addition, the use of off-pump
      CABG is also considered to achieve a better renal function than on-pump CABG.

PMID- 11842546
TI  - [Cases of death after surgery for pathologic stage I non-small cell lung cancer].
AB  - We clinically examined cases of death from pathologic stage I non-small cell lung
      cancer with the aim of improving the 5-year survival rate after surgery for this
      condition. The subjects were 70 patients with p-stage IA (20 cases of death) and
      59 patients with p-stage IB (26 cases of death) from among those who underwent
      surgery for p-stage I non-small cell lung cancer between 1986 and 2000. 1) Of 30
      patients who died from p-stage I lung cancer, 20 had distant metastases and 10
      had recurrence in the thoracic cavity. Of 16 patients who died from other
      diseases, 5 had respiratory organ disease, 5 had cancers of other organs and 6
      had circulatory organ disease. 2) Of 30 patients who died from p-stage I lung
      cancer, 20 (66.7%) had distant metastases, with lung metastasis occurring most
      frequently, in 10 of them (33.3%). The most common cause of death of patients
      with p-stage IB lung cancer was recurrence in the thoracic cavity. 3) The mean
      durations of survival (mean +/- standard deviation) after surgery for lung cancer
      of the patients who died from p-stage I lung cancer (30 patients) were 36.3 +/-
      22.2 months for the 20 patients with distant metastases and 26.2 +/- 14.3 months
      for the 10 patients with recurrence in the thoracic cavity, the difference
      between groups was 10 months, but was not significant. 4) The 5-year survival
      rate in 45 patients who underwent p-stage IA mediastinal lymph node dissection
      was 83.1% whereas that in 25 patients without p-stage IB mediastinal lymph node
      dissection was 50.9% showing a significant difference of 32.2% (p < 0.01). 5) The
      patients in p-stage IA who died from other diseases were all men (10 patients).
      The mean durations of survival after surgery for lung cancer in the patients who
      died from other diseases were 35.2 +/- 19.0 months in the patients with
      respiratory organ disease, 37.0 +/- 23.9 months in those with cancers of other
      organs and 60 +/- 19.1 months in those with circulatory organ disease. 6) The 5
      year survival rate after surgery in all cases of death was 76% in the patients in
      p-stage IA and 61.4% in those in p-stage IB. The 5-year survival rates in the
      patients excluding those who died from other diseases were 85% in the patients in
      p-stage IA (60 patients) and 60.3% in those in p-stage IB (53 patients) (p <
      0.01). 7) To improve the 5-year survival rate in the patients with p-stage IA
      lung cancer, it is necessary to prevent death from other diseases in men. It is
      still possible to improve the 5-year survival rate in the patients with p-stage
      IB lung cancer by raising the accuracy of mediastinal lymph node dissection
      during surgery.

PMID- 11842548
TI  - [Transportation for a pediatric heart transplant candidate to Germany].
AB  - A 8-year-old girl who underwent a total cavopulmonary connection as an one-staged
      repair for tricuspid atresia (Ic) had had a progressive dilated cardiomyopathy.
      Despite of any medical support, her left ventricular ejection fraction had been
      ranged from 10% to 20% since 4 months after Fontan operation. This patient was
      decided to apply for a heart transplantation in Germany 17 months after Fontan
      operation. An administration of the sufficient amount of inotropics and oxygen,
      volume resuscitation, reduction of the peripheral circulation at the time of take
      off, and a meticulous monitoring may contribute to the successful transportation
      of the critically ill patient.

PMID- 11842547
TI  - [A case of acute erythroblastic anemia due to infection with human parvovirus B19
      after coronary artery bypass grafting].
AB  - A 37-year-old male developed reticulocytopenia and leukopenia with fever from the
      11th patient day after coronary artery bypass grafting. Bone-marrow puncture
      revealed a marked decrease of erythroblasts and appearance of giant
      proerythroblasts. Thus, infection with human parvovirus B 19 (HPV-B 19) was
      suspected. At the onset of the disease, only IgM antibody was positive, but later
      IgG antibody also turned positive, and DNA of HPV-B19 was detected by polymerase
      chain reaction (PCR) from the bone marrow specimen of the patient. Then the
      patient was diagnosed with acute erythroblastic anemia due to infection with HPV
      B19. In this case, DNA of HPV-B19 was detected by PCR from a fibrin sealant used
      during operation. The fibrin sealant was found to be the source of infection.
      Fibrin sealants are used widely in the domain of surgery. Therefore, we should
      perform screening of plasma and make examination of the sealants, while paying
      attention to infections with HPV-B 19 in the future.

PMID- 11842549
TI  - [Bilateral sleeve upper lobectomy for metachronous squamous cell carcinoma of the
      lung; report of a case].
AB  - A 67-year-old man admitted to our hospital complaining cough. Bronchoscopic
      findings showed tumor at inlet of the left upper bronchus. Left upper sleeve
      lobectomy was performed. Six years 6 months later, he admitted to our hospital.
      Bronchoscopic findings showed tumor at inlet of the right upper bronchus. Right
      upper sleeve lobectomy was performed. He received radiation therapy, and
      discharged from the hospital 2 months after the operation. It is quite a rare
      case that the tumor lesions, to which bronchoplasty need to be applied, develop
      at 2 separate locations. This case proves that sleeve lobectomy can be applied to
      2 separate locations successfully.

PMID- 11842550
TI  - [A review of Japanese literatures concerning surgery for lung cancer with
      idiopathic interstitial pneumonia].
AB  - OBJECTIVE: The aim of the present study is to investigate the perioperative
      management of acute exacerbation of idiopathic interstitial pneumonia (IIP) after
      pulmonary resection for lung cancer. METHODS: We reviewed 5 Japanese literatures
      published from 1992 through 1998. The present study included 50 lung cancer
      patients with IIP, of which 3 were our cases and 47 were reported cases. RESULTS:
      Within 30 days after operation, acute exacerbation of IIP occurred in 12 cases
      (24.0%). Preoperative profiles (gender, age, smoking status, respiratory
      function, pathologic stage) of the exacerbated cases did not differ from those of
      non-exacerbated cases. The mean intraoperative PaO2 of the exacerbated cases was
      significantly higher than that of non-exacerbated cases (224 +/- 45.6 Torr vs 120
      +/- 41.2 Torr, p = 0.005). The rate of acute exacerbation increased with the
      extent of resection, that is 42.8% in pneumonectomy, 24.3% in lobectomy, and 0%
      in wedge resection although the difference was not significant. After acute
      exacerbation of IIP, all 12 cases were given high doses of steroids. However, 11
      cases died due to the disease progression (mortality rate = 91.7%). CONCLUSION:
      In order to establish the perioperative management for prevention of acute
      exacerbation of IIP, multi-institutional study is warranted on the basis of the
      present results (intraoperative FiO2, administration schedule of steroids etc).

PMID- 11842551
TI  - [Dissecting aneurysm of ventricular septum following acute inferior myocardial
      infarction].
AB  - Dissecting aneurysm of the ventricular septum as a complication after myocardial
      infarction (MI) is very rare. The patient was a 70-year-old women who was
      diagnosed with acute inferior MI. Three months after MI, catheterization showed a
      left ventricular aneurysm of the inferior wall, and left-to-right ventricular
      shunt flow was detected in the aneurysm. Echocardiography showed that the
      inferior left ventricular free wall was aneurysmal and dissected from the septal
      wall. Nine months after MI, chronic heart failure was uncontrollable by
      medication. At surgery, a tear (5 mm long) in the dissecting aneurysm of the
      ventricular septum was found and closed directly using 2 felt patches, and
      aneurysmectomy was performed using felt strips. The postoperative course was
      uneventful and she has been free from any complication for over 1 year.

PMID- 11842554
TI  - [Surgical treatment of aneurysm of the ductus arteriosus in the adult].
AB  - Aneurysm of the ductus arteriosus is rare, however, reports on this lesion have
      increased recently with the progress of thoracic aortic surgery in Japan. We
      report 3 male cases aged 58, 59, 73 years. Aneurysms and total aortic arch were
      replaced by artificial graft through median sternotomy using selective cerebral
      perfusion in 2 cases. Through left posterolateral thoracotomy using deep
      hypothermia with circulatory arrest, proximal descending thoracic aorta including
      the aneurysm was replaced in 1 case. Their postoperative courses were uneventful.
      Surgery for this lesion is safe and various surgical approaches and circulatory
      supporting methods can be selected depending on the size of aneurysm and
      associated lesions.

PMID- 11842552
TI  - [Comparison of mediansternotomy approach vs left thoracotomy approach for distal
      aortic arch aneurysm, and their postoperative complications].
AB  - We performed surgery for distal arch aneurysm in 22 patients; through a
      mediansternotomy in 11 patients (group M), and through a left thoracotomy
      approach in 11 patients (group L). If the distal position of an aneurysm was
      located at the pulmonary hilus without severe calcification of the ascending
      aorta, the mediansternotomy approach was chosen, whereas if we suspected that
      distal anastomosis would be difficult due to severe calcification of the
      descending aorta or aortic dissection type B, the left thoracotomy approach was
      selected. The mean cardiopulmonary bypass time (min.) was 229 +/- 56 in group M
      and 225 +/- 47 in group L, the mean circulation arrest time (min.) was 39 +/- 19
      in group M and 31 +/- 5 in group L, and the mean lowest temperature (degree C)
      was 22 +/- 1 in group M and 20 +/- 2 in group L. No severe cerebral or cardiac
      complications developed in any patients. The hospital mortality was 9% (1/11) in
      group M and 9% (1/11) in group L. Following discharge, 8 (73%) patients from
      group M and 9 (92%) from group L resumed a normal lifestyle. There were no
      significant differences between the 2 groups and the operative results of both
      approaches proved satisfactory. Therefore our indications for each surgical
      approach to treat distal arch aneurysm seemed appropriate.

PMID- 11842553
TI  - [A report of initial clinical use of left ventricular assist system with left
      ventricular inflow cannula for acute myocardial infarction].
AB  - Previous clinical results of left ventricular assist system (LVAS) therapy for
      cardiogenic shock due to acute myocardial infarction (AMI) are still
      unacceptable. Japanese LVAS was designed for left atrial inflow cannulation.
      However, to obtain higher initial LVAS flow and more decompression of left
      ventricular (LV) cavity and to avoid thromboembolic event, LV inflow cannulation
      is a preferable procedure. Therefore, LV inflow cannula for Japanese LVAS
      (Toyobo) was developed. We treated three AMI cases with Toyobo-LVAS using the new
      LV inflow cannula. All patients were in cardiogenic shock status since broad
      antero-septal AMI and treated with percutaneous cardio-pulmonary support before
      the LVAS installation. The LVAS was effective for recovery from cardiogenic shock
      status and multiple organ failure. Two patients died because of serious LVAS
      associated complications such as bleeding (case 1, 8 days) and cerebral
      thromboembolism (case 2, 45 days). One of them was assisted for 202 days and
      underwent second operation. Sixty days after removal of LVAS, the patient died
      due to sepsis. The technique of LV inflow cannulation is improved through our
      experiences. However, our result suggests that renovation of the regimen for anti
      coagulation and anti-septic therapy are necessary.

PMID- 11842556
TI  - [A case of quadricuspid aortic valve associated with coronary artery disease].
AB  - A 65-year-old man with aortic regurgitation was found to have a quadricuspid
      aortic valve. Surgical correction consisted of aortic valve replacement with a 21
      mm Hyper dynamic plus St. Jude Medical valve and coronary revascularization of
      LAD and the first diagonal branch. During the operation, a quadricuspid aortic
      valve with 1 smaller and 3 larger cusps and normal coronary orifice were noticed.
      Accurate information by the transesophageal echo proved to be quite valuable. Our
      case is one of 43 cases which have been reported in Japan.

PMID- 11842555
TI  - [Esophageal rupture just after the graft replacement of thoracoabdominal aorta
      for chronic aortic dissection].
AB  - A 51-year-old man with thoracoabdominal aortic aneurysm (DeBakey IIIb type
      chronic aortic dissection) first underwent the graft replacement of thoracic
      aorta with elephant trunk technique. Postoperatively, the residual false lumen
      just distal to the inserted graft as an elephant trunk enlarged in a short
      period, and it compressed the esophagus. He underwent the second graft
      replacement of thoracoabdominal aorta 2 months after the first surgery. Just
      after the second surgery, he had the esophageal rupture probably because of
      direct damage due to the enlarged aneurysm and loss of the arterial blood supply
      due to the graft replacement. He died of bleeding from the distal anastomosis
      because of the uncontrolled graft infection. It may have to be kept in mind that
      the esophageal rupture after the graft replacement could be one of the reason of
      the graft infection when the aortic aneurysm severely compressed the esophagus
      preoperatively.

PMID- 11842557
TI  - [A case of atypical aortic coarctation with mitral and aortic regurgitation and
      ascending aortic dilatation].
AB  - A 67-year-old female presented with dyspnea on exertion as a chief complaint.
      Diagnosed as having severe mitral regurgitation, aortic regurgitation, dilatation
      of the ascending aorta and atypical coarctation due to aortitis syndrome, she
      underwent mitral valve replacement, aortic valve replacement, ascending aorta and
      hemiarch replacement and ascending aorta-abdominal aorta extraanatomical bypass
      in one stage. Pathologically, typical findings of aortitis syndrome were not
      observed in the wall of the ascending aorta and aortic valve, but cystic
      medionecrosis was noted in the wall of the ascending aorta. Follow-up
      observations are needed for the remaining aortic wall.

PMID- 11842558
TI  - [A case of elderly in shock due to ruptured stanford type A acute aortic
      dissection with cardiac tamponade].
AB  - An 87-year-old female in shock was referred to our hospital. Emergency chest
      computed tomography and echocardiography showed a dissecting aneurysm of the
      ascending aorta and remarkable epicardial effusion. She was diagnosed as having
      rupture of Stanford type A acute aortic dissection with cardiac tamponade and an
      emergency operation was performed. While anesthesia was administered, cardiac
      arrest occurred and the chest was opened. We managed to establish an extra
      corporeal circulation and performed graft replacement of the ascending aorta with
      GRF glue. The patient followed a satisfactory postoperative course and was
      discharged from the hospital at the 48th postoperative day. The proper indication
      for operation and minimally invasive procedure enabled us to operate on the
      elderly patient.

PMID- 11842559
TI  - [A case of paraffinoma after plombage with spinal paralysis].
AB  - A 55-year-old woman was presented with large left-sided chest wall mass and
      spinal paralysis. She had undergone pleural plombage using paraffin for pulmonary
      tuberculosis at age 40 years. Thoracotomy was performed and all paraffin was
      removed. Paraffin provoked granulomatous change (paraffinoma) and invaded to
      vertebral canal. She remains well at 16 months postoperatively without spinal
      paralysis.

PMID- 11842561
TI  - Tips to increase success for teaching online: communication!
AB  - Advancement in technology and the World Wide Web have allowed student learning
      capabilities to expand to unexpected horizons. The majority of today's younger
      students are computer literate; therefore, new styles of teaching and learning
      are rapidly developing. Online education is in demand, and universities are
      rushing into the competitive e-learning marketplace for students. Currently, 6000
      accredited college courses are offered online, and 84% of 4-year universities are
      predicted to offer online courses by 2002. Faculty are expected to expand their
      teaching styles to include teaching online courses. It is estimated that only 10%
      to 15% of universities have avoided online programs. Some faculty resist this
      teaching strategy because of problems encountered when teaching online. Few
      articles address issues to overcome problems in online education in the nursing
      literature. This article provides tips on getting a course up and running using
      the acronym COMMUNICATION. Faculty can use these recommendations to assist them
      in the development of their online courses.

PMID- 11842560
TI  - [A resected case of solitary fibrous tumor of the pleura].
AB  - A 45-year-old female with solitary fibrous tumor (SFT) of the pleura was
      reported. Chest X-ray and CT scan on admission showed a large tumor in the right
      thoracic cavity. A preoperative needle biopsy was performed. The microscopic
      appearance of biopsied specimen revealed many spindle cells. And an
      immunohistochemical study was positive for CD 34 and negative for keratin,
      epithelial membrane antigen, alpha-smooth muscle actin, S-100 protein. So SFT was
      strongly suspected and an operation was performed. A tumor arised from the
      visceral pleura of right middle lobe and was pedunculated. The tumor was 13 x 10
      x 7.5 cm in size. An immunohistochemical study of the tumor was positive for CD
      34, and negative for SMA, ki-67. From these immunohistochemical stainings and
      microscopic findings, the tumor was diagnosed as SFT. An immunohistochemical
      study of the tumor seems to be very useful for the diagnosis of SFT.

PMID- 11842562
TI  - The 19th Annual International Nursing Computer and Technology Conference.

PMID- 11842563
TI  - Trade in your call center for an integrated medical contact center. Smart network
      technology solutions breakdown cost barriers--and create opportunities.

PMID- 11842564
TI  - OpenClinical.

PMID- 11842565
TI  - [Methods to evaluate occupational risk in industrial medicine].
AB  - The authors present methods to evaluate occupational risk in industrial medicine.
      Those methods are based on MACs and MALs with consideration of WHO and ISO
      concepts, European instructions and other countries' experience. The authors
      justified hygienic criteria for evaluation and classification of working
      conditions, quantitative criteria to evaluate links of health disorders and work,
      methods to analyze structure and degrees of occupational risk, to analyze
      etiology relationships between work conditions and health disorders. The article
      covers based categories of occupational risks according to socially valuable
      medical and biologic parameters. Methodology is a basis for realization of new
      Federal Laws on safety and occupational medicine.

PMID- 11842566
TI  - [Comparative analysis of respiratory function in miners suffering from
      anthracosilicosis and silicosis].
AB  - The authors revealed differences in pulmonary volumes, bronchial patency of
      bronchi at various levels, integral time of air transit in individuals having
      early anthracosilicosis and silicosis signs vs in healthy miners. During stage 1
      of anthracosilicosis and silicosis respiratory function progressively
      deteriorates and demonstrates moderate disorders. When compared to
      anthracosilicosis ones, patients having polymetallic dust silicosis showed more
      significant decrease of the studied parameters.

PMID- 11842567
TI  - [On mechanisms underlying bronchial obstruction in chronic dust bronchitis in
      workers of deep coal mines].
AB  - Healthy miners demonstrated increased relative levels of lysophosphatidyl choline
      and especially phosphatidyl inositol subunits. Metabolism of the latter could
      result in membrane accumulation of inositol triphosphate leading to cytoplasmic
      calcium increase and to bronchial smooth muscles contraction. Oral 20% choline
      chloride solution lowers bronchospasm in dust bronchitis patients with decreased
      serum subunits of phosphatidyl inositol and increased serum levels of
      phosphatidyl choline.

PMID- 11842568
TI  - [Influence of facultative irritants on pathogenesis of occupational skin diseases
      (review of literature)].

PMID- 11842569
TI  - [Children's health as a subject to sanitary and hygienic monitoring].
AB  - Sanitary and hygienic monitoring in town near Moscow evaluated health of children
      living in areas under various ecologic circumstances. The results proved that
      living near automobile roads and in town's industrial district is associated with
      considerably lower health state of the children. Increased level of acoustic
      exposure in the district corresponds to more frequent appeals to medical
      establishments for cardiovascular care.

PMID- 11842570
TI  - [Features of surfactant system in pulmonary tuberculosis in patients with
      occupational risk for pneumoconiosis].

PMID- 11842571
TI  - [Hygienic characteristics of workplace air pollution with fibrogenic aerosol
      during enriched sand production].

PMID- 11842572
TI  - [Value of new diagnostic technologies in assessing prognosis for occupational
      diseases].
AB  - The review covers recent literature data on value of various diagnostic tools in
      evaluating prognosis for occupational morbidity, course and outcomes of
      occupational diseases. Special attention is focused on various forecasting
      patterns of occupational morbidity, on genetic markers for propensity to and
      resistance against occupational diseases, on ultrasound methods of vascular
      examination, on new X-ray densitometry of bones, on novel biochemistry methods.

PMID- 11842573
TI  - A practical approach. Maine Medical Center works toward HIPAA compliance as part
      of an enterprise-wide IT strategic plan.

PMID- 11842574
TI  - IT in the ED. The nature of emergency department medicine means specific and
      comprehensive IT needs for clinicians.

PMID- 11842575
TI  - Teaching future physicians. Technology, academics and patient care join forces in
      a mobile world.

PMID- 11842576
TI  - At the speed of EDI. Physician practice converts to EDI and slashes both its
      claims turnaround and accounts receivable days.

PMID- 11842577
TI  - Assessing risk based on episodes of care. Software helps MCOs identify future
      risks and rally resources.

PMID- 11842578
TI  - Influencing physician practice variation. The future of evidence-based medicine
      portends use of information that is cumulative and evolutionary, not static.

PMID- 11842579
TI  - What works: speech recognition. Talking it through. Busy physical therapy
      practice converts from manual transcription to voice recognition.

PMID- 11842580
TI  - What works: document management. Image this. Document imaging carves a clear path
      to automation for Louisville group practice.

PMID- 11842581
TI  - What works: staff scheduling. Matching skill levels to unit needs. The Johns
      Hopkins Hospital creates a successful master schedule in obstetrics units with
      the help of technology.

PMID- 11842582
TI  - What works: wireless. Reaping the benefits of wireless. Minnesota hospital
      consortium improves patient care with bedside network access.

PMID- 11842584
TI  - Emergency department systems HotList.

PMID- 11842583
TI  - Conveying an effective message in voice mail or e-mail.

PMID- 11842585
TI  - Write-offs: doing it right the first time.

PMID- 11842586
TI  - Ocular inflammatory disease: use of topical and systemic anti-inflammatory
      agents.

PMID- 11842587
TI  - Pharmacological considerations in the treatment of glaucoma.

PMID- 11842588
TI  - Update on refractive surgery.

PMID- 11842589
TI  - Topical ocular allergy medications.

PMID- 11842590
TI  - Prevention and treatment of diabetic retinopathy and age-related macular
      degeneration.

PMID- 11842591
TI  - An update from the Veterinary Drugs Directorate.

PMID- 11842593
TI  - Primary hyperparathyroidism and concurrent hyperthyroidism in a cat.
AB  - A cat was presented for anorexia and vomiting. Hyperthyroidism and primary
      hyperparathyroidism were diagnosed. A thyroid adenoma and parathyroid adenoma,
      respectively, were responsible for these conditions. Unilateral thyroidectomy and
      parathyroidectomy successfully resolved both disorders.

PMID- 11842594
TI  - Evaluation and treatment of an adult quarter horse with an unusual fracture of
      the humerus and septic arthritis.
AB  - Humeral fractures are rare and usually carry a guarded prognosis in adult horses.
      This paper describes the evaluation and the successful surgical management of a
      fracture of the lateral supracondyloid crest and part of the epicondyle of the
      humerus in an adult quarter horse.

PMID- 11842592
TI  - Antimicrobial drug use and resistance in dogs.
AB  - Fifteen years (1984-1998) of records from a Veterinary Teaching Hospital were
      analyzed to determine whether antimicrobial drug resistance in coagulase-positive
      Staphylococcus spp. (S. aureus, S. intermedius) isolated from clinical infections
      in dogs has increased, and whether there has been a change in the species of
      bacteria isolated from urinary tract infections in dogs. In coagulase-positive
      Staphylococcus spp., a complex pattern showing both increases and decreases of
      resistance to different classes of antimicrobial drugs was observed, reflecting
      the changing use of different antimicrobial drug classes in the hospital over a
      similar period (1990-1999). In canine urinary tract infections identified from
      1984 to 1998, an increase in the incidence of multiresistant Enterococcus spp.
      was apparent, with marginal increases also in incidence in Enterobacter spp. and
      in Pseudomonas aeruginosa, both of which, like Enterococcus spp., are innately
      antimicrobial-resistant bacteria. A survey of directors of veterinary teaching
      hospitals in Canada and the United States identified only 3 hospitals that had
      any policy on use of "last resort" antimicrobial drugs (amikacin, imipenem,
      vancomycin). Evidence is briefly reviewed that owners may be at risk when dogs
      are treated with antimicrobial drugs, as well as evidence that some resistant
      bacteria may be acquired by dogs as a result of antimicrobial drug use in
      agriculture. Based in part on gaps in our knowledge, recommendations are made on
      prudent use of antimicrobial drugs in companion animals, as well as on the need
      to develop science-based infection control programs in veterinary hospitals.

PMID- 11842595
TI  - [A case of zoonosis associated with Streptococcus equi ssp. zooepidemicus].
AB  - A sexagenarian couple operating a dairy farm, where there were also many horses,
      suffered a severe respiratory infection associated with the bacterium
      Streptococcus equi ssp. zooepidemicus. The investigation revealed that the source
      of infection was due to contacts with a horse having an infected wound from which
      we isolated this zoonotic agent.

PMID- 11842596
TI  - Thyroid carcinoma and hyperthyroidism in a dog.
AB  - A 10-year old spayed, female Labrador retriever, with an 8-month history of
      weight loss, increased heart rate, and hyperactivity, was diagnosed with
      hyperthyroidism and a thyroid neoplasm. Thyrotoxic heart disease is documented in
      this case.

PMID- 11842597
TI  - Perirectal abscess, colic, and dyschezia in a horse.
AB  - A quarter horse gelding with intermittent colic was diagnosed with a perirectal
      abscess and dyschezia. Rectal ultrasonography identified a multiloculated, fluid
      filled mass. A perirectal abscess was diagnosed when the mass ruptured and
      drained into the rectum. The abscess was treated successfully with warm soapy
      water enemas and trimethoprim and sulfamethoxazole.

PMID- 11842598
TI  - Sudden mortality caused by cardiac deformities following seining of preharvest
      farmed Atlantic salmon (Salmo salar) and by cardiomyopathy of
      postintraperitoneally vaccinated Atlantic salmon parr in British Columbia.

PMID- 11842599
TI  - Fractures involving the distal extremity of the femur: Part 2--the mature
      patient.

PMID- 11842600
TI  - Practice success: the challenge of recruiting and retaining technicians.

PMID- 11842601
TI  - History and clinical signs.

PMID- 11842602
TI  - Assessing the need for booster vaccination.

PMID- 11842603
TI  - An ethicist's commentary on equating productivity and welfare.

PMID- 11842604
TI  - A resources for veterinarians on recognizing and reporting animal abuse.

PMID- 11842605
TI  - [The role of neuropeptide Y in anxiety].
AB  - Neuropeptide Y (NPY), one of the most abundant peptides in the mammalian brain,
      is implicated in the control of many physiological processes. It is also
      suggested the involvement of NPY in several neuropsychiatric illnesses. This
      review summarizes the present knowledge concerning the role of NPY in anxiety and
      discusses probable sites and receptors involved in the anxiolytic-like effect of
      NPY as well as interactions between the NPY and corticotropin-releasing factor
      (CRF) systems. The possible role of the NPY system in human psychopathological
      conditions associated with anxiety is also reviewed. Based on our data, we
      suggest that the NPY system is involved in antianxiety effects of diazepam and
      buspirone.

PMID- 11842606
TI  - [Symptoms profile of mixed anxiety and depressive disorder].
AB  - The paper describes symptoms of mixed depressive and anxiety disorder (ICD-10).
      The study was carried out in three medical dispensaries: two psychiatric (42
      persons) and one primary care (62 persons). Patients with or without anxiety and
      depressive symptoms were included. Exclusion criteria was: psychoactive substance
      abuse, physical diseases affecting mental state, and mental disorders other than
      anxiety or mood disorders. A total of 104 patients (65 women and 39 men in mean
      age of 41.1 years) were inquired with General Health Questionnaire (GHQ-30),
      Global Assessment of Functioning (GAF) and diagnostic questionnaire based on
      Schedules for Clinical Assessment in Neuropsychiatry, Version 2.0. There was no
      pattern of symptoms specific for mixed disorder that could be a basis for
      operational criteria. The most frequent were symptoms of generalised anxiety
      disorder (GAD), depression and dysthymia. The most specific symptoms, selected
      using discriminant analysis were: (1) difficulty in concentrating, (2) feeling
      mentally tense, (3) feeling of hopelessness or despair, (4) shortening of breath,
      (5) lowered mood, (6) feeling dizzy, unsteady, faint, or light headed; (7) early
      waking up, (8) nightmares, (9) dry mouth, (10) hot flushes or cold chills, (11)
      frequent tearfulness. The results contribute to the concept that mixed depression
      and anxiety disorder is closely related to generalised anxiety disorder (GAD).

PMID- 11842607
TI  - [Anxiety and depression in bronchial asthma].
AB  - The aim of the study was to establish the frequency and follow the clinical
      course of depression and anxiety in patients with bronchial asthma. 57 patients
      (37 atopic and 20 nonatopic) with mild and moderate bronchial asthma and 53
      subjects matched for age and sex as control groups were included in the study.
      The following questionnaires: Beck Depression Inventory (BDI), State-Trait
      Anxiety Inventory (STAI) and Hospital Anxiety and Depression Scale (HADS) were
      used to evaluate anxiety and mood state. The level and prevalence of anxiety and
      depression were significantly higher in both groups of asthmatics in comparison
      to healthy subjects. Symptoms were mild and moderate. Nonatopic patients were
      more depressed and anxious than atopics.

PMID- 11842608
TI  - [Anxiety-depressive disorders in women after hysterectomy. Literature review].
AB  - In the common opinion amongst woman, the surgical removal of the uterus and
      ovaries can be a cause of limited physical and sexual activity and have an effect
      on their attractiveness. The majority of women after hysterectomy can be
      permanently depressed and can also show symptoms of mixed anxiety-depressive
      disorder. The review of literature allows for an assumption that the topic of
      anxiety and depression should not be underrated, by treating it as an exaggerated
      theme, as some researchers do. By considering the research quoted in this paper
      the collected directions of diagnostic and therapeutic procedures undertaken by
      the psychiatrist and psychologist can be used before the planned operation.
      Special consideration must be given to patients who have a history of affective
      disorders or sexual abuse. Pharmacotherapy and psychotherapy should applied in
      order to prevent post-operative affective disorders.

PMID- 11842609
TI  - [Anxiety-depressive disorder in women after hysterectomy. Own study].
AB  - Hysterectomy is a surgical procedure that significantly affects the quality in
      which the operated person views herself, lowers self-esteem and brings about
      changes in the quality of life. The results of the presented study show the
      necessity of a more accurate and specific dealing with the problem of affective
      disorders and anxiety states in women who have undergone such an operation. The
      course of the post-operative period and the return of the patients to full health
      are largely affected by their psychological state and the quality of life they
      experience. A successful (in a medical sense) surgical procedure is not a
      guarantee of the bringing back health in a holistic sense. The results of studies
      and clinical observations show that half of the group of women operated suffer
      from anxiety-depressive disorders as a cause of the operation, and a quarter of
      all those operated require specialist help. No psychological preparation for the
      operation, absence of closest people in the decision making before the operation,
      lack of knowledge on the surgical operational-span, lacking psychological aid
      after the operation--all these can significantly affect the rehabilitation and
      the process of regaining the social functions. It appears vital to introduce a
      psychological programme and special care taking of the women who declare having
      symptoms which appear to lead to the development of depressive disorders. The
      appearance of depressive symptoms post-operatively as well as the earlier
      presence of affective disorder symptoms can be prognostic in the further
      development of the disorder. The early diagnosis of the affective disorder and
      the higher level of anxiety in women post-hysterectomy and the fast application
      of appropriate treatment can inhibit further symptom elevation and persistence.
      Catamnestic studies on women post-hysterectomy due to non-oncologic causes will
      allow seeing the dynamics of the changes in the affective disorders at different
      time intervals from the operation.

PMID- 11842610
TI  - [Assessment of short-term neuropsychologic changes after normothermic versus
      hypothermic coronary artery bypass grafting].
AB  - BACKGROUND: Coronary artery bypass grafting (CABG) is one of the main methods of
      treatment of coronary artery disease. Neuropsychological testing is a sensitive
      method for quantitative assessment of cognitive dysfunctioning following
      cardiopulmonary bypass. The aim of the present clinical study was to evaluate the
      neuropsychologic changes in CABG patients, operated with normothermic or
      hypothermic cardiopulmonary bypass (CPB). METHODS: Neuropsychological changes
      were assessed in 33 first-time CABG patients before and 3-10 days after surgery.
      Patients underwent CABG with hypothermic (Gr. H, n = 17) or normothermic (Gr. N,
      n = 16) CPB with standard anesthesia. Neuropsychological performance was assessed
      using a well-established battery of 10 tests. A neuropsychological test battery
      includes: Digit Span-subtest of WAIS-R (PL), the Trail Making Test, Raven Test,
      Benton, Bourdon, Verbal Fluency (F,A,S), Turm von Hanoi, Rey Auditory Verbal
      Learning Test, Supermarket, WAIS-R (PL) Digit Symbol-subtest of WAIS-R (PL). All
      patients completed the test for perception, attention, immediate and delayed
      verbal and visual memory, visual and verbal learning, problem-solving strategies,
      abstraction, recognition, word fluency, visual- motor coordination and
      psychomotor speed. For comparison, the incidence of decline using the 1.5
      standard deviation (at least in 2 tests) also was calculated. RESULTS: Comparing
      the reliable change and SD methods, statistically significant differences in the
      incidence of decline were observed in 6 of the 10 neuropsychological measures.
      Patients' scores showed a significant deterioration in concentration of
      attention, immediate verbal memory, psychomotor speed, visuoconstructive tasks
      and verbal learning. Neuropsychological deficits were found in 66.7% of patients
      after surgery. Post-operative deficits were not associated with the method used
      (normothermia or hypothermia).

PMID- 11842611
TI  - [An episode of depression in a patient with coronary artery disease].
AB  - An episode of depression in a patient with Ischaemic Heart Disease is presented.
      The patient had undergone coronary angioplasty with optimal results. The clinical
      picture of the depressive disorder consisted mainly of chest pain complaints in
      the cardiac area, which made the diagnosis all the more difficult. The
      application of antidepressive treatment caused the depressive symptoms together
      with the chest pain to disappear. A therapeutic success was achieved owing to the
      good co-operation between the invasive cardiologist and the psychiatrist.

PMID- 11842612
TI  - [Dysfunction of the hypothalamic-pituitary-adrenal axis in adolescents after a
      suicide attempt].
AB  - The subject of the research were two populations: 84 adolescents aged 14-21,
      after sui cidal attempts (ASA--drug overdose), never treated psychiatrically, and
      30 adolescents after accidental intoxication (ACI). The objective of this
      research was to find whether there is a relation between the observed suicidal
      behaviors, psychic disorders and dysfunction of the hypothalamo--pituitary-
      adrenal axis. In each patient the plasma levels of cortisol and ACTH were
      assessed, and also the Dexamethasone Suppression Test (DST) was made. It was
      found that most patients in the ASA group were females. Additionally, in this
      group statistically higher levels of cortisol after DST were found, comparing to
      the ACI group. Considering the sex of patients, the differences of serum cortisol
      levels were significant only in females. We found that higher cortisol levels in
      ASA were related to diagnosed depressive disorders (mostly in females), presence
      of psychosocial and environmental problems, and elevated risk level of repeated
      suicidal attempt.

PMID- 11842613
TI  - [Detection of anti-Borna disease virus antibodies in patients hospitalized in
      psychiatric hospitals located in the mid-Western region of Poland].
AB  - Borna Disease Virus (BDV) is single stranded RNA virus, which may infect a wide
      range of animal species. Manifestations of the experimental BDV infection show
      some resemblance to psychopathological symptoms of mental disorders in humans.
      Several reports suggest the higher prevalence of anti-BDV antibodies in
      psychiatric patients than in healthy controls. However, the seroprevalence of
      anti-BDV antibodies varied due to the different serological methods used in the
      previous studies. Electrochemiluminescence Immunoassay (ECLIA) is a recently
      developed, highly specific method of detecting antibodies directed toward two BDV
      proteins: p24 and p40. We used the ECLIA method for the assessment of
      seropositivity in 946 psychiatric patients hospitalized in the psychiatric
      hospitals in the western part of Poland. All patients were clinically diagnosed
      with ICD-10 criteria. Anti-p40 antibodies have not been found in the studied
      sample. We found anti p-24 antibodies in 23 cases, which give the seroprevalence
      rate of 2.4%. This result is consistent with the outcome of Japanese population
      assessment, done with the same methodology. The seropositive cases did not show
      diagnostic specificity. We did not find statistically significant gender
      differences in rate of seropositivity. The seroprevalence of anti-BDV antibodies
      was not significantly different in patients of urban and rural residence, and in
      patients of different age groups. This is the first demonstration of anti-BDV
      antibodies in the Polish population of patients hospitalized in psychiatric
      hospitals.

PMID- 11842614
TI  - [Psychological factors in psoriasis: review of literature].
AB  - Psoriasis is an inflammatory and proliferative disease, which is seen in most
      classifications of psychocutaneous disorders as being mainly due to genetic and
      environmental factors. Over decades of observation, physicians and patients have
      learned that it's course is strongly influenced by psychological stress. Review
      of literature shows, however, that this relationship is multifactorial. Psoriasis
      itself may cause depression as a stigmatizing disease. Also there is evidence
      that depression and anxiety disorders can be the cause of psoriasis. Because of
      this fact, additional treatment with psychotherapy and/or medication may be
      advisable and worth further exploration.

PMID- 11842615
TI  - [The ethical code of psychotherapist].

PMID- 11842616
TI  - [Visceral neuroses: clinical approaches to the problem].
AB  - Visceral neuroses are regarded as psychosomatic pathology represented by
      functional symptom complexes common for both psychic (personality,
      psychopathologic disorders of anxietyphobic, affective, hypochondriac spectrum)
      and somatic pathology. Two hundreds fourteen patients: 67 with hyperventilation
      syndrome (HVS), 77 with Da Costa syndrome (DCS), 70 with irritable bowl syndrome
      (IBS) have been studied. The study suggest that visceral neuroses represent a
      group of independent diseases. In contrast to converse neuroses, a topical
      projection (respiratory, cardiovascular system, gastrointestinal tract, etc.) of
      visceral neuroses reflects not only a psychosomatic disorder's specificity but
      also the course and prognosis regularities inherent to them. HVS course is wavy
      with periodic exacerbations and incomplete remissions, DCS one is phased
      (remissive), IBS is chronic without distinct phases and intervals. HVS and DCS
      are comorbid to milder psychic (personality and anxiety phobic disorders) and
      somatic pathology. IBS is associated with not only more severe mental disorders
      (overvalued, hypochondriac, affective) but also with chronic somatic diseases
      (alimentary system).

PMID- 11842617
TI  - [Differential diagnostic criteria of lateral amyotrophic sclerosis].
AB  - Differential diagnostic criteria of lateral amyotrophic sclerosis (LAS) and
      lateral amyotrophic sclerosis syndrome were elaborated on the basis of complex
      investigation, including EMG and blood plasma trace element analysis. Fifty-two
      patients (25 with LAS, 27 with LAS syndrome) have been examined, the diagnoses
      being established according to the World Neurologist Federation criteria. LAS
      syndrome was stipulated by a vascular spinal cord lesion-discircular myelopathy;
      in some cases vascular deficit was combined with an inherent narrowness of spinal
      cord channel. All patients were followed-up with a 6-month interval. The results
      of the study allow to differentiate LAS and LAS syndrome of vascular genesis,
      already during the first medical examination.

PMID- 11842620
TI  - [Pharmacokinetic aspects of carbamazepine and valproic acid using in reproductive
      age women with epilepsy].
AB  - Dynamics of carbamazepine and valproic acid concentrations in the middle of
      follicular and lutein menstrual cycle phases has been studied in women with
      epilepsy, aged 21-30 years. Nineteen patients were treated with valproic acid
      (Depakine 900-2000 mg/day), 35--with carbamazepine (500-1200 mg/day). All the
      patients have been treated during at least 6 months, the remission being observed
      during the last 3 months. Control group consists of 17 healthy age-matched women
      with no positive familial history of nervous and endocrine diseases.
      Carbamazepine and valproic acid concentrations were measured in blood serum using
      high-performance liquid chromatography. Blood for analysis was donated on an
      empty stomach in the morning before the next dose (i.e. at the lowest
      concentration) and two hours after the drug taking. Mean carbamazepine
      concentrations (4-12 mcg/ml) in the women with epilepsy were adequate when the
      day dose was more than 10 mg/kg. Carbamazepine concentrations during lutein phase
      were significantly lower (p < 0.03), comparing to those in the follicular phase.
      However, in the lutein phase, progesterone, which concentration was ten times
      higher is follicular one, has an additional effect, acting as anticonvulsive
      agent. Valproic acid concentrations do not significantly differ in the lutein and
      follicular phases that allows Depakine using in catamenial epilepsy.
      Practitioners are not recommended to overestimate the anti-epileptic drug (AED)
      concentration monitoring because the usage of the lower AED individual
      therapeutic dose, not achieving even the mean therapeutic drug concentrations, is
      acceptable. This seems to be of extremely importance for women with potential
      maternal role function.

PMID- 11842619
TI  - [Clinical aspects of "folie du doute"].
AB  - "Folie du doute" related to obsessive disorders manifests with doubts about
      managing habitual actions, reality of what is happening and existence of
      surrounding subjects; ruminations, indecision emerged as incapability to choose a
      definite behavior line. Sixty-six patients, 27 men and 39 women (mean age 31.3
      years) have been examined. Three clinical "folie du doute" variants were
      distinguished: "repeated control" obsessions (doubts are realized by re-control
      of the actions committed); obsessive doubts defined by contrastive ideas of
      expedience for choosing the approach contrastive to the taken decision; anxious
      ruminations (lack of assurance in the past actions and obsessive doubts of the
      variants supposed-to-be). "Folie du doute" emerged in different psychic
      disorders, the first variant manifesting in the scope of neurotic-like
      schizophrenia; the second one--in psychogenic states or psychogenically-provoked
      exacerbations of psychopathic-like schizophrenia; the third one being regarded in
      the structure of cyclothymiac's depressive phases. In the clinical contest,
      "folie du doute" manifestation proves to be unfavorable prognostic marker.

PMID- 11842621
TI  - [Betaserc in symptomatic therapy of multiple sclerosis].

PMID- 11842618
TI  - [Non-psychotic mental disorders in opioid abusers].
AB  - The purpose of the study was to estimate the structure and prognostic value of
      mental disorders in opioid addiction. 173 males and 34 females aged 16-58 years
      with opioid addiction duration from 6 months to 14 years were studied. Mental
      disorders were mostly expressed at the peak of withdrawal state and in the early
      post-withdrawal period but they occurred at other stages of the illness. Anxiety
      was leading in the picture of psychic disturbances, representing some kind of "a
      psychopathologic background", on which other disorders (phobias, hypochondriac,
      psychopath-like and others) developed or intensified. Marked mental and physical
      discomfort intolerance dominates in personality change spectrum of the opioid
      users. The anxiety intensity did not correlate with withdrawal symptom-complex
      severity. But anxiety state plays an essential role in nonpsychotic disturbance
      formation and addictive disorders proper. Stable and progredient anxiety
      hypochondriac disorders determine a pathological development of the patient's
      personality and unfavourable disease prognosis.

PMID- 11842623
TI  - [Electroneuromyographic criteria of partial motor conduction block and temporal
      dispersion in patients with alcoholic polyneuropathy].
AB  - The aim of the investigation was to determine electroneuromyographic diagnostic
      criteria of conduction block (CB) and temporal dispersion on the basis of 78
      healthy volunteers and 82 patients with alcoholic polyneuropathy examination. We
      investigated motor fiber ulnar, median, peroneal and tibial nerves on distal
      segments of extremities at the level of forearm and leg, respectively. We
      determined a percentage of the maximal degree of negative peak (NP) and "peak to
      peak" amplitude reduction, the NP area and the total M-response as well as the
      degree of NP duration increase and the total M-response obtained from proximal
      nerve stimulation point versus to distal one. The area of M-response was shown to
      be the less changeable index, while the degree of amplitude, area and M-response
      duration changes depended on the nerve studied. The greatest changes of these
      parameters were revealed during a tibial nerve study in the controls and in the
      patients with alcohol polyneuropathy. The CB presence proves being identified
      when the proximal NP area reduction and the total M-response is over than 30 and
      35%, respectively. The temporal dispersion can be confirmed if NP duration
      increase is over than 30%. CB is likely suspected when the proximal NP area and
      the total M-response reduction is greater than 20 and 25% for the peroneal, ulnar
      and median nerves.

PMID- 11842622
TI  - [The use of normobaric hypoxia in the therapy of epilepsy].
AB  - The article concerns the usage of discrete normobaric hypoxic therapy as a way to
      enhance non-specific resistance in epilepsy treatment. The optimising effect of
      hypoxia on physiological functions of the patients with epilepsy consists in an
      increase of haemoglobin and erythrocytes in blood, less systole frequency, a
      systolic and diastolic pressure reduction, prolongation of a breathing hold
      during a Stange's test). As a result of these changes, the frequency of epileptic
      attacks decrease and normalization of behavioural responses was observed.

PMID- 11842624
TI  - [The analysis of serotonin receptor type 2A gene polymorphism in patients of
      different nationalities with acute alcoholic psychosis].
AB  - The analysis of Msp1 polymorphism (-1438G/A) in the promoter region of serotonin
      receptor type 2A (5HTR2A) gene has been conducted using polymerase chain reaction
      method in the men with an acute alcoholic psychosis of Russian and Tartar
      nationalities. The results obtained indicate the 5HTR2A gene is involved in
      development of the given pathology and allow to conclude that (1) 5HTR2A
      genotype's and allele's frequency distributions in Russians and Tartars do not
      significantly differ and correspond to those for the white Americans; (2) for the
      men of Russian nationality the genotype G/G is associated with the early onset of
      a chronic alcoholization and acute alcoholic psychosis development; (3) for the
      men older than 35 years of Russian and Tartar nationalities with genotypes
      carrying an allele G the relative risk of the given pathology is estimated as
      5.81.

PMID- 11842626
TI  - [Clinical aspects of late sequelae of birth-related brachial plexopathy in
      children].

PMID- 11842625
TI  - [Auditory evoked potentials in patients with schizophrenia and affective
      disorders].
AB  - Eighteen patients with schizophrenia and 18 patients with affective disorders
      (depression) underwent regisTration of auditory event-related potentials (ERPs)
      recording in oddball paradigm. All the patients were in remission. In both groups
      of the patients, the N100 ERPs amplitudes to non-target stimuli were
      significantly smaller and N200 and P300 latencies were longer than in 18 normals.
      In the patient's group with affective disorders, prolongation of P200 and N100
      ERPs latencies to target stimuli has been found. The group of patients with
      schizophrenia was characterized by P300 amplitude reduction. The results show
      stimuli processing decrease in patients with affective disorders, while in
      patients with schizophrenia a cognitive function disturbance was recorded.

PMID- 11842627
TI  - [Blood erythrocyte antigens as a factor of genetic predisposition to alcoholism
      and drug addiction].

PMID- 11842628
TI  - [A rare form of demyelinating polyneuropathy: hereditary neuropathy with
      predisposition to pressure palsies].

PMID- 11842629
TI  - Six Sigma effort paying dividends for CT hospital.

PMID- 11842630
TI  - Predictive modeling, integrated DM emerge as popular strategies.
AB  - The traditional managed care strategies of capitation and selective provider
      contracting are losing their punch, as members have demanded broader networks and
      providers have pushed demands for fee-for-service payment. Health plans looking
      to regain an advantage can capitalize on two emerging disease management
      strategies--both of which rely on analyzing member data.

PMID- 11842631
TI  - Computer simulation improves on laboratory benchmarking.
AB  - Benchmarking of hospital laboratory services is about to take a new twist, as
      computer simulations allow managers to see proposed efficiency improvements in
      action before investing in new equipment or staff changes.

PMID- 11842633
TI  - Ninth Circuit examines False Claims Act's Civil penalties and treble damages
      provisions. United States v. Mackby.

PMID- 11842632
TI  - North Philadelphia Health System employs handhelds to check data.
AB  - Quality control professionals typically do their work after patients have been
      seen and treated. But North Philadelphia Health System (NPHS) in Philadelphia,
      PA, is using wireless technology to collect and analyze data while the patient is
      still in the hospital, giving the quality control department the opportunity to
      improve care on the spot.

PMID- 11842634
TI  - Courts rule physicians had no duty. Prosise v. Foster.

PMID- 11842635
TI  - Seventh Circuit reverses dismissal of physician's ADA claim. Mattice v. Memorial
      Hospital of South Bend Inc.

PMID- 11842636
TI  - Office of Inspector General approves hospital-physician surgery center joint
      venture.

PMID- 11842637
TI  - Recent cases and decisions.

PMID- 11842639
TI  - Perspectives. People problems plague switch to chronic care models.

PMID- 11842638
TI  - Surgical and specialty hospitals: a legal primer.

PMID- 11842640
TI  - 10 good questions for understanding nursing research.

PMID- 11842641
TI  - Opening the door--biofeedback and meditation.

PMID- 11842642
TI  - Recognizing the sublime in the familiar.

PMID- 11842643
TI  - Aromatherapy for health professionals.

PMID- 11842644
TI  - 'Regulatory lag' in Minnesota.

PMID- 11842645
TI  - Introduction to the Joint Global Ocean Flux Study (JGOFS).

PMID- 11842647
TI  - What do we know about maternal-fetal attachment?
AB  - A review of the literature suggests that there are three critical attributes
      related to the concept of maternal-fetal attachment, including cognitive,
      affective, and altruistic attachment. Cognitive attachment is the desire to know
      the baby. Affective attachment is the pleasure associated with thoughts of or
      interaction with the fetus. Altruistic attachment refers to a desire to protect
      the unborn child. Existing measurements on maternal-fetal attachment are
      developed based on low-risk and white pregnant women and previous research has
      not yet resulted in a consistent theoretical model. Future research should focus
      on development of culturally sensitive instruments and combining qualitative and
      quantitative measures to broaden theoretical understanding of the concept.
      Nursing assessment of maternal-fetal attachment is an on-going process. The
      nurse's role is to reassure those who have developed attachment to their fetuses
      and to motivate those who are unaware of or unconcerned about their attachment to
      their fetuses. Collecting data from different attributes of attachment helps
      nurses identify each woman's attachment patterns and areas of concern.

PMID- 11842646
TI  - A new vision of ocean biogeochemistry after a decade of the Joint Global Ocean
      Flux Study (JGOFS).

PMID- 11842648
TI  - Effects of S-adenosyl-L-methionine on liver damage in experimental obstructive
      jaundice.
AB  - S-adenosyl-l-methionine (SAMe) is a naturally occurring molecule distributed
      throughout the body tissues, including the liver. It acts as a methyl group donor
      and as an enzyme activator in a number of biochemical reactions. Methionine is
      metabolized in the liver, where it is converted to SAMe by SAMe-synthetase. In
      patients with liver diseases, these pathways are impaired because of the
      decreased contents of glutathione, the major abnormality being a reduction in
      SAMe-synthetase activity. Exogenous SAMe may overcome the results of impaired
      SAMe-synthetase activities. We conducted this study to evaluate the effect of
      SAMe administration on liver damage induced by biliary obstruction. Rats with
      common bile duct ligation exhibited abnormal liver functions, increased lipid
      peroxide levels, and decreased reduced glutathione contents when compared with
      the shammed-controls, which indicated that there was oxidative stress in rats
      with obstructive jaundice; however, SAMe application improved these injuries.
      There were significant alterations of the levels of amino acid profiles in
      animals with obstructive jaundice. The ratio between branch chain and aromatic
      amino acid was depressed, which indicated that the condition of liver was
      worsening, but SAMe administration improved these alterations significantly. In
      conclusion, SAMe administration alleviated the liver damage, indicating an
      important hepatoprotective effect of this methyl donor.

PMID- 11842649
TI  - Antitumor and immunoenhancing activities of polysaccharide from culture broth of
      Hericium spp.
AB  - The fruiting body and culture broth of many edible mushrooms contain water
      soluble polysaccharides. Numerous researchers have reported that these
      polysaccharides have immunoenhancing effects. In this study, Hericium erinaceus
      and Hericium laciniatum were separately cultivated in a shaker at 25 degrees C
      for 25 days. Polysaccharides were extracted from the culture broth. The molecular
      weights were larger than 1 x 10(5) k Da and their polysaccharide components were
      mainly glucose in H. erinaceus and galactose in H. laciniatum. Furthermore, we
      investigated these two purified water-soluble polysaccharides for their anti
      artificial pulmonary metastatic tumor and immunoenhancing effects in ICR mice.
      The results revealed that both polysaccharides had significant anti-artificial
      pulmonary metastatic tumor effects in mice (p < 0.05). Additionally, the
      polysaccharide from H. erinaceus was more effective than that from H. laciniatum.
      However, both of the polysaccharides enhanced the increase of T cells and
      macrophages. The numbers of CD4+ cells and macrophages were significantly higher
      in the test group than in the control group (p < 0.05). From our results, no
      differences were found between the two purified water-soluble polysaccharides in
      the antitumor effects and immunoenhancing activities (p > 0.05).

PMID- 11842650
TI  - Insulin action and insulin secretion in newly diagnosed type 2 diabetic patients.
AB  - To clarify the insulin action and insulin secretion in newly diagnosed type 2
      diabetic subjects, we investigated insulin and C-peptide response to an oral
      glucose tolerance test (OGTT) in 15 newly diagnosed type 2 diabetic patients and
      17 healthy subjects. For insulin action, we found fasting hyperinsulinemia (8.4
      +/- 0.8 vs. 6.0 +/- 0.5 microIU/ml, p = 0.014), higher insulin resistance by
      homeostasis model assessment (HOMA) (4.33 +/- 0.2 vs. 1.34 +/- 0.1
      microIU/ml.mmol/l, p < 0.001), and lower insulin sensitivity index (ISI) (51.0 +/
      0.7 vs. 104.0 +/- 0.8, p < 0.001) in newly diagnosed diabetic patients compared
      to normal subjects. For insulin secretion, the increments of AUCI (area under
      curve of insulin) and AUCC-P (area under curve of C-peptide) (increment of AUCI:
      26.1 +/- 1.4 vs. 82.8 +/- 4.5 microIU/ml.hour, p < 0.001; increment of AUCC-P:
      3.9 +/- 0.2 vs. 11.4 +/- 0.6 ng/ml.hour, p < 0.001), insulin secretion by HOMA
      model (20.7 +/- 1.2 vs. 79.1 +/- 3.8 IU/mol, p < 0.001), and ratio of 30 min
      increment of fasting insulin to glucose during OGTT (1.14 +/- 0.1 vs. 13.1 +/-
      0.5 IU/mol, p < 0.001) were significantly lower in the newly diagnosed diabetic
      patients than normal subjects. In addition, body mass index (BMI) in our type 2
      diabetes is relatively lower (24 +/- 0.65 kg/m2) than those in western countries.
      These findings revealed poor insulin action and decreased insulin secretion in
      relatively less obese Taiwanese with newly diagnosed type 2 diabetes.

PMID- 11842651
TI  - Rehabilitation fees, length of stay and efficiency for hospitalized stroke
      patients: a preliminary study based on function-related groups.
AB  - The purpose of this study was to examine the relationships between severity of
      disability and factors such as rehabilitation fees, length of stay and efficiency
      for hospitalized stroke patients. One hundred and seven first-time stroke
      patients were studied consecutively for this study. They were recruited from a
      rehabilitation ward in a university medical center during 1997. Functional
      ability was evaluated using the Functional Independence Measure (FIM) instrument
      on admission and discharge. Stroke patients who presented with similar degrees of
      disability were put together using the admission FIM score (FIM Function-Related
      Groups, FIM-FRGs) for further analysis. Twenty-eight (26.2%) patients examined
      were categorized as severely disabled (scored 18-36), 48 (44.8%) moderately
      disabled (scored 37-72) and 31 (29.0%) mildly disabled (scored 73-126). The
      average expense on rehabilitation fees, for the average rehabilitation length of
      stay (LOSR) of 34.7 +/- 16.7 days, was NT$ 27,645 +/- 13,812. The FIM score
      improved from 56.8 +/- 24.2 on admission to 76.6 +/- 26.2 at discharge, with a
      rehabilitation efficiency index (EIR) of 0.7 +/- 0.7. Further analysis indicated
      that there were significant differences among the three disability groups on
      rehabilitation fees and LOSR while EIR was unaffected. The findings of this study
      suggest that FIM-FRGs can differentiate different rehabilitation needs in terms
      of rehabilitation fees and LOSR; therefore, a prospective case payment system
      based on FIM-FRGs is suggested for stroke rehabilitation reimbursement scheme in
      the future.

PMID- 11842652
TI  - Superior mesenteric artery syndrome associated with hereditary motor and sensory
      neuropathy type II--a case report.
AB  - A 14-year-old girl with superior mesenteric artery (SMA) syndrome associated with
      hereditary motor and sensory neuropathy (HMSN) type II is reported. The initial
      presentations of HMSN type II were developmental delay and gait disturbance at 2
      years of age. All deep tendon reflexes were absent. Nerve conduction velocities
      and left sural nerve biopsy all revealed axonal changes. Recently, she suffered
      from intermittent bilious vomiting and epigastralgia for 6 months. That caused
      body weight loss from 40 kg to 28 kg. Abdominal echography showed narrowed
      superior mesenteric artery angle. Upper gastrointestinal series revealed
      obstruction of third portion of duodenum. Accordingly, SMA syndrome was
      diagnosed. To the best of our knowledge, this case is the first report of SMA
      with HMSN type II in the world. When a child with chronic neurological disease
      presents with intermittent vomiting, SMA should be considered as a disease entity
      of differential diagnosis.

PMID- 11842653
TI  - Early recognition of cerebral hyperperfusion syndrome after carotid stenting--a
      case report.
AB  - The hyperperfusion syndrome is a recognized complication of carotid
      endarterectomy. Reports of cerebral hyperperfusion injury following internal
      carotid artery angioplasty and stenting are few We report a case of 76-year-old
      hypertensive man who was admitted to our hospital for assessment 2 years after
      experiencing an ischemic stroke of right hemisphere. Angiography confirmed 60%
      stenosis of left internal carotid artery (ICA). Percutaneous transluminal
      stenting of left internal carotid artery was performed without any immediate
      complications. Two hours after the procedure, the patient suddenly deteriorated.
      Computed tomography (CT) of the brain revealed extensive intracerebral hemorrhage
      and he died 5 days later. There was precipitating migranous headache, and his
      blood pressure was moderately elevated at the time of deterioration. Sentinel
      headache could solely indicate the early sign of hyperperfusion injury after
      carotid stenting, especially in the presence of arterial hypertension. Patients
      with sentinel headache after angioplasty should be recognized early and they
      deserve intensive study for other features of cerebral hyperperfusion injury and
      prompt early management.

PMID- 11842654
TI  - Tentative surgical repair of leaking filtering bleb with amniotic membrane
      transplantation--a case report.
AB  - To repair a traumatic leaking cystic bleb in a 50-year-old male patient who had
      received multiple glaucoma filtering surgeries with the application of mitomycin
      C, an amniotic membrane covered over the leaking bleb and sutured it to the
      adjacent conjunctiva with 10-0 nylon was done. The anterior chamber gradually
      formed after the amniotic membrane transplantation (AMT) and intraocular pressure
      returned to the level before trauma. Three weeks after the operation, the
      amniotic membrane was removed. No more leakage from the bleb was observed during
      four months follow-up. However, another bleb revision surgery was performed later
      to repair recurrent bleb leakage. Although conjunctival advancement or free
      conjunctival autograft have been reported to repair leaking bleb successfully,
      the simple primary method of using AMT is still encouraged in repair of a
      ruptured bleb with tentative maintenance of adequate filtration.

PMID- 11842655
TI  - Chasing a miracle: why infertile women continue to stay in treatment.
AB  - This article discusses the reasons infertile couples continue to remain in
      infertility treatment. Through a qualitative research approach, using eight open
      ended questions, the author interviewed a convenience sample of fourteen women in
      a large Midwestern academic health center reproductive endocrinology group
      practice, to identify reasons that influenced their decision to stay in
      treatment. The desire to have one's own children was the motivating force which
      helped sustain a sense of hope in these women fueled by the advanced technology
      advocated by their physicians. Support for these women were mostly from spouses
      and family members with friends with children not being very supportive. The lack
      of patient education was seen as a very negative influence by most of the
      participants.

PMID- 11842656
TI  - Emergency 911: America was called....
AB  - This author expresses her thoughts and feelings about the terrorist attack on the
      World Trade Center in New York City carried out on September 11, 2001.

PMID- 11842657
TI  - Description and evaluation of a health education program for women offenders.
AB  - One percent of the population of the United States consists of women offenders,
      who are at-risk for numerous preventable diseases. Since health promotion is not
      a high priority when women are incarcerated, the author used group education as
      one way of increasing participants' knowledge and self-efficacy. Results
      indicated that a group health education program is an excellent way to change
      participants' knowledge and self-efficacy in a women's prison population.

PMID- 11842658
TI  - Case of the month. More than meets the eye.

PMID- 11842659
TI  - Size matters. Understanding morbid obesity & its associated complications.
AB  - America is facing a health crisis that will test the limits of EMS resources and
      resourcefulness in coming years. In the United States, obesity is second only to
      cigarette smoking as the leading cause of preventable death--causing more than
      300,000 deaths annually. It has also been implicated in the dramatic rise in
      diabetes and heart disease.

PMID- 11842660
TI  - Caring for Karen. How one patient changed an EMS agency's overall transport
      attitude.

PMID- 11842661
TI  - Handle with care. Specialized methods & devices for moving morbidly obese
      patients.

PMID- 11842662
TI  - If the bubble bursts.... EMS response to aortic aneurysms & dissections.
AB  - An aortic disease patient is typically an older male with a history of
      atherosclerosis and hypertension. He might have Marfanoid characteristics, a
      history of cocaine or methamphetamine abuse or history of syphilis.
      Alternatively, suspect dissection in a pregnant female with complaints consistent
      with possible aortic problems. During your assessment, zero in on the patient's
      anatomy. Include aortic phenomena in your differential for chest and back pain.
      Take blood pressures in both arms. Search the abdomen for pulsatile masses, and
      be wary of hoarseness and Horner's syndrome.

PMID- 11842663
TI  - New approach seeks to conquer physician resistance to DM.

PMID- 11842664
TI  - Online program for treating chemical dependency breaks down barriers.
AB  - Providers caring for patients with substance abuse difficulties know how hard it
      is to get those patients the kind of help they need. Beyond insurance
      difficulties and a significant shortage of treatment programs, many patients lack
      the time needed to enter into traditional programs or they have privacy concerns
      that keep them from accessing this type of care. A new online approach to
      treatment seeks to address all these barriers while providing a traditional 12
      step approach to care.

PMID- 11842666
TI  - Beyond guidelines: tool arms physicians with critical knowledge at the point of
      care.
AB  - Any generalist knows that it is virtually impossible to stay on top of all new
      developments that impact management of chronic disease. Further, the complexity
      involved with individual cases makes optimal care an even tougher challenge.
      However, a growing number of practitioners and organizations are addressing this
      problem by making use of a unique software tool that matches current knowledge
      and advice with specific patients at the point of care. Early studies show the
      approach can go a long way toward making sure evidence-based guidelines are
      followed while offering the potential for substantial cost savings.

PMID- 11842665
TI  - New tools help behavioral health providers boost quality while documenting value.
AB  - One California-based provider of behavioral health services was in that position
      until it implemented a system that not only documents the progress of treatment
      for payers, but also helps the organization provide better care by supplying
      continuous updates on patient status. The system uses two research-based tools
      that look at critical triggers as well as a patient's overall level of distress.
      See how implementation of this innovative approach has facilitated provider/payer
      discussions while fueling quality improvement.

PMID- 11842667
TI  - Preventing 9-1-1 calls.

PMID- 11842668
TI  - Chemical and biological weapons.

PMID- 11842669
TI  - BORSTAR: border patrol EMS.

PMID- 11842670
TI  - Surviving tough times: how to ride out an uncertain economy.

PMID- 11842671
TI  - The anatomy and physiology of respiration.

PMID- 11842672
TI  - The expert take: assessing the terrorism issues facing EMS. Interview by John
      Erich.

PMID- 11842673
TI  - The rules have changed.

PMID- 11842674
TI  - PASG: bad wrap or bad rap?

PMID- 11842675
TI  - Advanced airway techniques.

PMID- 11842676
TI  - Blind nasal intubation.

PMID- 11842677
TI  - Health care workers shape up.

PMID- 11842678
TI  - Building better practice: legal, ethical, and other concerns.

PMID- 11842679
TI  - The tyrannies of palliative care.

PMID- 11842680
TI  - The safe use of syringe drivers for palliative care: an action research project.
AB  - A palliative care team in north Scotland identified serious drug errors occurring
      in the local health-care trust. These were connected with the use of variable
      rate syringe drivers (IVAC P100) to deliver pain and symptom management rather
      than the more suitable Graseby MS26. An action research approach was taken to
      effecting change. An educational workshop was set up which 23 nurses attended.
      Clinical support was provided and 3 months later an evaluation was carried out.
      Of the 13 nurses who had used an MS26, most were able to correctly follow the
      process of setting up the driver and had made appropriate observations, but drug
      calculations were a problem. Change was stated to have taken place in seven
      clinical areas but the degree of change was variable. Facilitators and obstacles
      to the change process are identified and recommendations made for the next round
      in the action research cycle.

PMID- 11842681
TI  - A programme of individualized and self-administration of medicines in a hospice.
AB  - Hospice care is changing. Statistics show that people are surviving longer with
      cancer and many more are choosing to be cared for in the community. The hospice
      is no longer an institution solely for the care of people in the terminal phase
      of their illness but is involved in the palliation of symptoms, so allowing
      patients to return home to independent living. It was with this in mind that we
      recognized the need for the introduction of a programme of individualized and
      self-administration of medication at the hospice where we work. Although self
      administration of medication was our first aim, the individuality of care brought
      about by its introduction, the adaptations required to include all palliative
      care patients and the resulting enhancement of holistic patient care, has become
      the main thrust of the project. This article will explore the term 'self
      administration of medication'; the evidence of its use in other areas of health
      care; the rationale for change within the hospice movement; consequences to
      practice; and the staged implementation of a programme of individualized and self
      administration of medication.

PMID- 11842682
TI  - Cancer in Western Australian Indian families: concerns and coping strategies.
AB  - Discussion with families of Indian clients with cancer living in Western
      Australia and their anecdotal reports of stress related to care lead to the
      development of this descriptive, qualitative study. In particular, the study
      addresses the concerns of Western Australian families of Indian clients with
      cancer and the coping strategies they employed. Six family members participated
      in face-to-face interviews. Content analysis revealed a four-phase process that
      family members described in response to the cancer diagnosis: initial reactions,
      immediate concerns, ongoing concerns, and coping strategies used. Culturally
      specific observations and recommendations are offered for nursing practice and
      further research.

PMID- 11842683
TI  - Student nurses' knowledge of palliative care: evaluating an education module.
AB  - There is evidence that education in palliative care in the UK is somewhat patchy
      and that this important area of health care should be given a greater emphasis in
      the nursing curriculum. This article describes an evaluation of a palliative care
      module taken by a group of third year student nurses. The effect of the module
      was evaluated using the palliative care quiz for nursing (PCQN), administered at
      the beginning and at the end of the module. The results demonstrate that the
      students significantly increased their understanding of aspects of pain and
      symptom control. In particular, they became knowledgeable about adjuvant
      therapies and opioid use. In contrast to previous studies, the students rejected
      the 'fear of addiction' associated with opioid use. Deficits in knowledge
      included side-effects of codeine, use of sedation and the use of placebos. The
      results support the need to develop a compulsory module in palliative care that
      is formally assessed and includes a palliative care placement. This would enable
      comprehensive and systematic coverage of palliative care in the undergraduate
      nursing curriculum.

PMID- 11842684
TI  - Hypnotherapy in a specialist palliative care unit: evaluation of a pilot service.
AB  - There is evidence that hypnotherapy may have an application in the palliative
      care setting by relieving stress and helping patients to cope with their illness
      and the prospect of dying. It may also be of benefit to health professionals
      working in this sometimes stressful field. This article reports on the audit of a
      pilot hypnotherapy service for patients, carers and staff at a specialist
      palliative care unit. The audit explored the demand for hypnotherapy, the
      practicalities of providing the service and identified benefits as perceived by
      the clients and the therapist. Evaluation methods included questionnaires for
      quantifiable and qualitative data. The study was conducted over 5 months and
      involved 11 clients (seven staff and four patients). The main findings depicted
      unanimous positive coping and relaxation benefits to the clients. At the end of
      the therapy, 82% felt it had assisted in improving the presenting problem and 91%
      felt it had been of benefit in general. Further issues are discussed such as the
      therapeutic relationship, non-attendance and the environment used during the
      sessions.

PMID- 11842686
TI  - [What is the status of nursing care after introduction of the new reimbursement
      system?].

PMID- 11842687
TI  - [Rationing in public health service].

PMID- 11842688
TI  - [Graduate and continuing education in ambulatory care and inpatient geriatric
      nursing].

PMID- 11842685
TI  - Rural palliative care needs: a survey of primary care professionals in Powys,
      Wales.
AB  - The county of Powys in rural Wales has a population of about 125,000 people and
      no district general hospitals. In 1999, 12 Macmillan general practitioner
      clinical facilitators were appointed as part of a pilot project aiming to provide
      a coordinated framework for the commissioning of specialist cancer and palliative
      care services, extended clinical care to cancer and non-cancer patients, and an
      educational intervention to raise the standards of generalist palliative care. A
      survey of facilitators, general practitioners, district nurses and community
      hospital nurses was undertaken early in the project. Palliative care formed a
      small but significant part of respondents' workload. Specialist palliative care
      services were seen as helpful but distant from the patients. Pain and symptom
      control were seen to be problematic in patients with diagnoses other than cancer.
      Services that provided 24-hour nursing care at home were thought to be in need of
      development by most respondents.

PMID- 11842689
TI  - [Ethical responsibility of nursing occupations].

PMID- 11842690
TI  - [No fear of hospital discharge. Home care services for elderly tumor patients
      according to the palliative treatment concept].

PMID- 11842691
TI  - [Superiority of Sandimmune Optoral C-2 monitoring].

PMID- 11842692
TI  - [Whooping cough--origin of a pathogen].

PMID- 11842694
TI  - Health care 2010: the "new rules" of health care strategy and management.

PMID- 11842695
TI  - The "new rules" of health care management in 2010.

PMID- 11842696
TI  - Long-range strategies for sustainable competitive advantage.

PMID- 11842697
TI  - Caring about carepaths.
AB  - This short paper describes an experiment in the use of clinical pathways for
      orthopaedic patients at Cairns Base Hospital. We rapidly found they improved the
      management of cost and quality, and that there were many beneficial side-effects.
      Our approach was subsequently adopted in other departments. Unfortunately,
      external support for further developments has not been forthcoming and we argue
      that this may be an unwise move.

PMID- 11842698
TI  - Contemporary issues in Australian midwifery regulation.
AB  - This paper reports on research that examined the Nurses' Acts, regulations and
      current policies of each state and territory in Australia, in order to determine
      their adequacy in regulating the education and practice of midwifery. This is
      part of a three-year study (Australian Midwifery Action Project) set up to
      identify and investigate barriers to midwifery within the provision of mainstream
      maternity services in Australia. Through an in-depth examination and comparison
      of key factors in the various statutes, the paper identifies their effect on
      contemporary midwifery roles and practices. The work assessed whether the current
      regulatory system that subsumes midwifery into nursing is adequate in protecting
      the public appropriately and ensuring that minimum professional standards are
      met. This is of particular importance in Australia, where many maternity health
      care services are seeking to maximise midwives' contributions through the
      development of new models of care that increase midwives' autonomy and level of
      accountability. A lack of consistency and evidence of discrepancies in the
      standards of midwifery education and practice regulation nationally are
      identified. When these are considered alongside the planned development of a
      three-year Bachelor of Midwifery, due to be introduced into Australia in mid
      2002, there exists an urgent need for regulatory change. The need is also
      identified for appropriate national midwifery competency standards that meet
      consumer, employer and practitioner expectations, which can be used to guide
      state and territory regulations. We argue the importance of a need for change in
      the view and legal positioning of the Australian Nursing Council and all Nurses
      Boards regarding the identification of midwifery as distinct from nursing, and
      substantiate it with a rationale for a national and consistent approach to
      midwifery regulation.

PMID- 11842699
TI  - Carving an identity for allied health.
AB  - This paper outlines the development, growth and performance of the Division of
      Allied Health at Lottie Stewart Hospital, Sydney. It discusses the choice of a
      suitable organisational model, the findings from three evaluations conducted and
      a summary of the significant outcomes of the Division. An early version of this
      paper was presented at the 4th National Allied Health Conference in March 2001.

PMID- 11842700
TI  - Employees' perceptions of workplace change.
AB  - Change is endemic, but it creates fear in the workplace. In this study, five
      people from a health care organisation were interviewed to gain a better
      understanding of their concerns in the workplace. Each person regarded the
      effects of workplace change somewhat differently in variety and intensity but in
      general terms they all identified two major spheres of influence. Each sphere
      represents a complex dynamic relationship of several effects. The first, which is
      at an individual level, includes feelings and attitudes, and behavioural,
      psychological and social effects. The second, which is at an organisational
      level, includes culture, leadership, decision making and strategy implementation.
      Communication and education were viewed as key elements that facilitated the
      change process. In the surveyed organisation, service closure was viewed as the
      overriding concern that dominated most participants' perceptions of change.
      Additional research is required to ascertain if this model can be generalised to
      other workplace environments.

PMID- 11842701
TI  - Management and the creation of occupational stressors in an Australian and a UK
      ambulance service.
AB  - Qualitative methods were used to explore the aetiology of occupational stress
      experienced by on-road ambulance officers. The researcher found that the way in
      which a service is organised and its officers valued can create and reproduce
      workplace stressors that are as causative of occupational stress as the often
      acknowledged occupational specific stressors like night shifts, irregular work
      hours and witnessing human trauma and tragedy. These stressors thought to be
      intrinsic to the work of ambulance officers were found to have an organisational
      dimension.

PMID- 11842702
TI  - Hands-on nursing and carepaths: a commentary.

PMID- 11842703
TI  - The provision of hanbang herbal medicine in the Korean community in Australia:
      entrepreneurial or caring for fellow Koreans?
AB  - This study explores the underlying factors that sustain the practice of herbal
      medicine in a non-English speaking background (Korean) community in Australia.
      Qualitative study was undertaken of 8 herbal doctors' practice of herbal
      medicine, their understanding of Korean immigrants' life and work involvement,
      and the use of herbal medicine, using semi-structured interview schedules. The
      demand for herbal medicine is linked to Korean immigrants' involvement in manual
      work or long working hours irrespective of their qualifications. Hanbang tonic
      medicine is a way to maintain their health--that is, a capacity to work. Although
      hanbang doctors claim that hanbang medicine differs from biomedicine, they share
      more similarities than differences under the current economic environment. The
      increasing interest in complementary therapies has ramifications on people's
      health and health care industry. Government and professional regulations on
      complementary therapies could be developed in close consultation with relevant
      stakeholders. Health care practice in the migrant community is an area to be
      approached with caution.

PMID- 11842704
TI  - Caring about carepaths in Queensland and Bulgaria: a commentary.

PMID- 11842705
TI  - Hospital patient libraries and information services in Australia.
AB  - In order to find out how many and what kind of Hospital Patient Libraries exist
      in Australia I placed a "Request for Information" on our national electronic
      discussion list entitled 'aliaHealth'. This discussion list has presently nearly
      300 subscribers. Most of them are located in Australia, but they also come from
      Canada, Germany, Hong Kong, the United Kingdom and New Zealand. The e-mail
      address for 'aliaHealth' is: aliaHealth@alianet.alia.org.au. The result of my
      enquiry was rather poor: there are three Hospital Patient Libraries in Western
      Australia, one in Queensland and two in Victoria. The criterion was that the
      Library or Patient Information Service had to be located within the Hospital
      grounds. The six Libraries or Information Services are described in detail.

PMID- 11842706
TI  - Falls Clinics in Australia: a survey of current practice, and recommendations for
      future development.
AB  - The aim of this study was to identify common themes and differences in structure
      and function of Falls Clinics in Australia, to provide a framework for planning
      future activity. A paper-based survey was circulated to 20 identified Falls
      Clinic services throughout Australia in late 2000. Fifteen responses (75%) were
      received, although two of the 15 Clinics were not operating at the time of the
      survey, and so their responses were not included. Nine of the Clinics had
      commenced operation since 1998. Staffing commonly included a physiotherapist,
      geriatrician, and an occupational therapist, with the comprehensive
      multidisciplinary assessment process taking an average of 130 minutes. Although
      standard assessment tools were used by more than half of the Clinics, there were
      no universally applied assessment tools. Waiting lists for initial assessments
      ranged up to 16 weeks (average 6 weeks). Most Clinics instituted a number of
      management options themselves, but also used a range of existing community
      services to provide some of the planned interventions. Limited formal evaluation
      of the effectiveness of Clinics was reported. Recommended future activity
      included increasing staff levels and operating times for Clinics to more
      adequately meet identified need, increased networking and data sharing between
      Clinics, and a greater emphasis on research and staff training. We conclude that
      the recent increase in the number of Falls Clinics around Australia has occurred
      in a relatively unstructured manner, with many differences in staffing, operation
      and evaluation. There is a need for improved communication and standardisation of
      core procedures and assessment tools to facilitate best practice in all Clinics,
      and to provide a framework for a systematic evaluation of the effectiveness of
      Falls Clinics in Australia.

PMID- 11842707
TI  - Using non-geriatric clinical indicators in a department of rehabilitation and
      aged care.
AB  - We describe an audit using Gastroenterology Clinical Indicators (CIs) to measure
      quality of care for older patients with gastrointestinal haemorrhage. The
      gastroenterology CI for gastroscopy within 24 hours of admission was 60%, it was
      70% for diagnosis of a cause of acute gastrointestinal bleeding after upper
      gastroscopy, and it was 30% for death after blood transfusion in a geriatric
      restorative unit. We discuss whether it is appropriate for a hospital department
      (Geriatric Medicine) to use the CIs for the specialty (Gastroenterology)
      providing the service to measure the quality of service being provided. This may
      be a useful approach given the trend towards cost recouping between different
      clinical departments.

PMID- 11842708
TI  - Caring about carepaths: on locus of control, holons and weltanschauung.

PMID- 11842709
TI  - Cost comparison of hospital- and home-based treatment models for acute chronic
      obstructive pulmonary disease.
AB  - This trial compared the cost of an integrated home-based care model with
      traditional inpatient care for acute chronic obstructive pulmonary disease
      (COPD). 25 patients with acute COPD were randomised to either home or hospital
      management following request for hospital admission. The acute care at home group
      costs per separation ($745, CI95% $595-$895, n = 13) were significantly lower (p
      < 0.01) than the hospital group ($2543, CI95% $1766-$3321, n = 12). There was an
      improvement in lung function in the hospital-managed group at the Outpatient
      Department review, decreased anxiety in the Emergency Department in the home
      managed group and equal patient satisfaction with care delivery. Acute care at
      home schemes can substitute for usual hospital care for some patients without
      adverse effects, and potentially release resources. A funding model that allows
      adequate resource delivery to the community will be needed if there is a move to
      devolve acute care to community providers.

PMID- 11842710
TI  - Concurrent opioid dependence and mental health problems: a review of the issues
      for general practice.
AB  - The literature is reviewed on the issue of concurrent opioid dependence and
      mental health problems within the general practice setting. People with such
      problems have poorer personal, clinical and social outcomes than people with
      either mental health or drug and alcohol (D&A) problems alone. Mental health and
      drug services operate from different policy systems and are generally not co
      ordinated with each other, leaving the onus on the patient to move effectively
      through health systems. The common statement that GPs are ideal health
      professionals to manage concurrent problems is contrasted with the evident
      barriers in general practice such as lack of time, knowledge, skills and
      confidence. Models for managing concurrent problems tend towards shared care.
      However, these models either have received mixed evidence (e.g. consultant
      liaison psychiatry) or are amenable to development but remain untested (e.g. co
      ordinated care, community health centre programs). The Enhanced Primary Care
      items introduced in 1999/2000 may provide an incentive for GPs to participate in
      shared care arrangements with other health professionals. However, there is a
      need for mechanisms to increase the links between GPs and other health services.

PMID- 11842711
TI  - A neurobehavioural-informed approach to the use of clinical competencies in
      supporting the community-based care of individuals with multi-axial diagnoses.
AB  - Individuals with multiple diagnoses most often present with social difficulties,
      with either aggressive or withdrawn behaviour predominating. In individuals with
      behaviours that represent changes at a neural level, and in those with comorbid
      psychiatric diagnoses, these behaviours often represent obstacles to
      rehabilitation. Consequently there is little consensus as to how such patients
      can be assessed, treated and interacted with, and so too there is little
      potential to improve outcomes with guided training. When multiple agencies are
      involved, such patients may 'fall between the cracks' and undergo prolonged and
      disempowering interventions with poor outcomes in the absence of individual
      programmes. This article addresses the core issue of empowerment in the
      assessment and community-based rehabilitation of patients with multiple mental
      health issues, and utilises a case report format to illustrate the methodology.

PMID- 11842712
TI  - Multi-presenter mental health patients in emergency departments--a review of
      models of care.
AB  - Only a small proportion of the treatment of mental illness occurs in an
      institution or hospital. By far the most significant treatment happens in the
      community and in the patient's own social and family environment. However, de
      institutionalisation of mental health services has brought increasing numbers of
      patients to the emergency department in need of psychiatric assistance. The
      traditional service model of emergency departments, focusing on physical illness
      and injury, is being challenged. The literature review identified numerous
      psychiatric service models in place but dramatically highlighted the lack of a
      specific service model addressing psychiatric patients who present on multiple
      occasions [multi-presenters] in emergency departments. At present, accurate data
      on the effects of multi-presentation of psychiatric disorders are not available.
      Recent international and local research into models of service delivery
      management and best practice is examined.

PMID- 11842713
TI  - Cost-effective clinical pathways at the Alfred Hospital: international lessons
      from Bayside Health, Australia.

PMID- 11842714
TI  - Thoughts on barriers and enablers for incorporating ordinary theorising into the
      community participation in health debate.

PMID- 11842715
TI  - Designing teams that work.
AB  - This paper describes the development of clinical improvement teams in a multi
      disciplinary acute health care setting. The process included an information
      gathering phase that enabled a match of team structure and leadership to staff
      skills and experience. It was found that an environment that supported
      collaborative practice and shared decision-making was critical to staff support
      of the teams and the outcomes achieved.

PMID- 11842716
TI  - Clinicians' contributions to healthcare management.
AB  - Primary tasks for clinical directors are to disseminate information to
      colleagues, provide feedback to senior professional managers, and to play key
      roles in strategic planning and resource allocation in health services. These
      tasks are seen to reduce barriers between clinicians and management. The
      application of clinical directorates across healthcare organisations is
      inconsistent and ambiguous. When set clear guidelines, clinical directors can
      impact on the decision-making process within senior management. As further
      applications of clinical directors in management occur, development of the role
      is required to realise the potential.

PMID- 11842717
TI  - Hospital utilisation expectancies in New Zealand, 1980-98.
AB  - The need to synthesise mortality and morbidity information to achieve a more
      global and relevant measure of population health status is well recognised, with
      health expectancy indices being the most common approach used to date. Using New
      Zealand hospital discharge and mortality data over the 1980-98 period, we
      introduce readers to a newly developed health index, the Hospital Utilisation
      Expectancy (HUE). We describe how HUE changes with age and over time. New Zealand
      national and regional trends are described. The methodological strengths of the
      measure and its applications in the health sector are discussed.

PMID- 11842718
TI  - Empirical comparison of DRG variants using cardiovascular surgery data: initial
      results of a project at 18 German hospitals.
AB  - In 2000, the responsibility for selecting a DRG variant for use in Germany was
      assigned to a body comprising representatives of hospitals and insurers called
      the Self-Administration Board (or Board in this paper). To help the Board, we
      applied cardiac surgery data from 18 German hospitals to eight different DRG
      variants. The error caused by bad coding quality could be minimized this way,
      since all diagnoses and procedures in cardiac surgery must be recorded for
      quality assurance purposes. To match the German code to the appropriate code
      required by the DRG variant, we created mapping tables whenever needed. As far as
      cardiac surgery is concerned, the Australian AR-DRG and the French GHM variants
      provided the best medical relevance, while the AR-DRG variant considered the
      level of severity better. Other variants would have to be updated to better
      reflect the level of medical complexity. Three main causes for wrong grouping
      could be identified for all systems: incomplete mapping, not enough reference to
      multidisciplinary treatments, and system construction problems.

PMID- 11842719
TI  - Identification of factors contributing to increased length of stay in two
      diagnosis related groups.
AB  - This paper discusses a study conducted to identify factors that contributed to
      increased length of stay for two diagnosis related groups (DRGs) and their
      consequential impact on nursing salaries. The study shows that three separate
      clusters of cost drivers (DRG-related, nurse-related, and patient-related)
      contributed to increased length of stay for DRG 177 (chronic obstructive airways
      disease) and DRG 367 (cholecystectomy without exploration of the common bile
      duct). It was not possible to establish a link between length of stay and nursing
      salaries due to lack of relevant data. The results of the study can be used to
      raise professional awareness to the difficulties encountered by nurse managers in
      controlling length of stay when there are substantial numbers of different DRGs
      in acute care wards. The results can also be used as a basis for conducting
      larger studies into DRGs with higher than expected lengths of stay.

PMID- 11842720
TI  - Why aren't clinicians caring about carepaths? A commentary.

PMID- 11842721
TI  - A critical review of rural medical workforce retention in Australia.
AB  - The problem of how best to recruit and retain doctors in rural and remote
      communities has led governments to adopt a range of medical workforce incentives,
      including retention grants. A comprehensive literature survey suggests that
      medical workforce retention has been poorly distinguished from other supply
      issues such as recruitment, and that its determinants and the process leading to
      retention are poorly understood. Such a knowledge gap is likely to limit the
      effectiveness of retention incentives. This article reports the results of this
      literature review, and advances a conceptual framework as the basis for ongoing
      research and evaluating how best to deliver effective retention interventions.

PMID- 11842722
TI  - [Heparin or aspirin in the treatment of acute cerebral infarction?].

PMID- 11842723
TI  - [The hypersomnia of Ambroise Vollard, exceptional art dealer and editor].

PMID- 11842724
TI  - [Liver abscess].
AB  - Liver abscesses are bacterial or parasitic. In a patient presenting with fever,
      fatigue and upper right abdominal pain, abdominal ultrasound must be performed to
      reveal a liver mass. Clinical history and serologies allow presumptive diagnosis.
      Pyogenic abscesses are mostly secondary to biliary tree infection. Pus aspiration
      and culture confirm the diagnosis. Gram-negative bacilli and anaerobes are the
      most frequent germs. Percutaneous drainage combined with antibiotics is the
      standard treatment. Earlier diagnosis, better techniques for bacterial culture
      and adapted treatment have improved prognosis. Amoebic abscesses are less
      frequent but their incidence is increasing in the presence of immunosuppressed
      state. The diagnosis is based on abdominal ultrasound and serology. Treatment is
      principally medical.

PMID- 11842725
TI  - [Hepatic granulomas of infectious origins].
AB  - Hepatic granulomas of infectious origin are due to several causes. Bacterial and
      rickettsial infections are the most frequent (mainly tuberculosis, infections due
      to atypical mycobacteria, Q fever). However parasitic and fungal infections may
      also be involved. Histological characteristics of the granuloma are sometimes
      suggestive of the cause, but the aetiological diagnosis often results from a
      careful confrontation of clinical, biological, and histological data. One should
      always have in mind the possibility of tuberculosis, where an effective treatment
      must be given as early as possible. The cause of granulomas remains unknown in
      approximately half the cases after careful investigations.

PMID- 11842726
TI  - [Bacterial perihepatitis].
AB  - The Fitz-Hugh-Curtis syndrome is a peri-hepatitis following a genital infection.
      It usually occurs in young women. Chlamydia trachomatis is the most frequent
      causal agent. Clinical signs include acute or recurrent pain in the right
      hypochondria. Liver tests are not modified and the sonographic examination is
      normal. Diagnosis can be suspected on the basis of serology, and formally
      established by laparoscopy showing violin string-like adhesions. Prolonged
      antibiotic treatment is effective.

PMID- 11842727
TI  - [Leptospiroses].
AB  - Leptospirosis is a worldwide zoonosis, that is most frequently encountered in
      tropical and subtropical areas. In France, during the last years, its incidence
      has increased. Epidemiology is conditioned by a wide animal reservoir. Important
      clinical polymorphism makes diagnosis difficult. Laboratory abnormalities such as
      increased serum C-reactive protein and triglycerides and suggestive. Early
      diagnosis is now possible by using polymerase chain reaction methods. Early
      treatment with an aminopenicillin can improve prognosis which remains poor,
      especially in case of renal or pulmonary involvement. Pathophysiology of the
      disease still needs to be thoroughly studied.

PMID- 11842729
TI  - [Visceral leishmaniases].
AB  - Leishmanioses are a group of infections caused by the protozoa Leishmania. Humans
      are infected by female sandfly bites. Leishmaniosis is found in Mediterranean
      Europe, America, Africa and Asia. Various clinical expressions are possible:
      visceral (kala-azar) or cutaneous (Old world cutaneous leishmaniosis). In
      Mediterranean Europe, visceral leishmaniosis with the classical triad,
      splenomegaly, pallor, fever, was traditionally a childhood disease whereas today
      the disease with atypical clinical expressions strikes immunocompromised
      patients. In these atypical forms of visceral leishmaniosis, diagnosis and
      treatment are particularly difficult. Leishmania-DNA research using polymerase
      chain reaction is often necessary to perform the diagnosis, and lipid-associated
      formulations of amphotericin B, rapidly effective and well-tolerated in patients
      without immunodeficiency, do not prevent recurrences in immunocompromised
      patients.

PMID- 11842728
TI  - [Schistosoma mansoni schistosomiasis].
AB  - Schistosomosis are parasitic diseases caused by blood flukes of the Schistosoma
      genus. The pathology of schistosomosis is mostly brought about by ova trapped in
      the tissues. In the liver, granuloma around ova eventually trigger periportal
      fibrosis and portal hypertension. In S. mansoni infection, the infection
      intensity and the onset of liver fibrosis are under distinct genetic control.
      Liver fibrosis is the main cause of death in the 20 millions individuals
      suffering from chronic schistosomosis. However, liver fibrosis is reversible if
      antischistosomal drugs are administered before the onset of severe hepatic
      insufficiency.

PMID- 11842731
TI  - [Psychology of choice behavior: medical application].

PMID- 11842730
TI  - [Non-viral liver infections in immunocompromised patients].
AB  - Bacterial, parasitic and fungal liver infections have been reported in severely
      immunocompromized patients. The liver is usually involved when the infection is
      disseminated. Clinical manifestations are non specific and commonly associated
      with increased in alcaline phosphatases serum level. Liver insufficiency and
      portal hypertension are very uncommon. Liver biopsy remains necessary for the
      diagnosis. Mycobacterial infections represent the major cause of liver infection
      in this population. Prevalence of biliary cryptosporidiosis and microsporidiosis
      in patients with AIDS has hugely declined since the use of highly active
      antiretroviral therapy. Liver fungal infections have been reported in patients
      with T lymphocytes dysfunction, are mainly related to Candida species, but remain
      infrequent.

PMID- 11842732
TI  - [Acute inflammatory polyradiculoneuritis (Guillain-Barre syndrome)].

PMID- 11842733
TI  - [Pelvic pain in women. Diagnostic orientation].

PMID- 11842734
TI  - [Splenomegaly. Diagnostic orientation].

PMID- 11842736
TI  - [Acute peritonitis].

PMID- 11842737
TI  - [Vertigo (and treatment)].

PMID- 11842735
TI  - [Hypoglycemia].

PMID- 11842738
TI  - [Asthma in children].

PMID- 11842739
TI  - Planning target volume and dose prescription in definitive radiotherapy for
      prostate cancer with favourable prognostic factors.

PMID- 11842740
TI  - Dose escalation for prostate cancer: which dose for which person?

PMID- 11842741
TI  - Outcome of patients undergoing radical cystectomy for invasive bladder cancer.

PMID- 11842742
TI  - Invasive bladder cancer: organ preservation by radiochemotherapy.

PMID- 11842743
TI  - Radiation, chemotherapy and transurethral surgery: an organ-sparing alternative
      to the radical cystectomy.

PMID- 11842744
TI  - T1G3 bladder cancer--the case for TUR and BCG.

PMID- 11842745
TI  - Radiochemotherapy for T1G3 bladder cancer.

PMID- 11842746
TI  - The technique of 125I permanent implants.

PMID- 11842747
TI  - Planning target volume definition in dose-escalation studies.

PMID- 11842748
TI  - Interstitial brachytherapy with permanent seed implants in early prostate cancer.
AB  - Excellent clinical results after permanent seed implantation have been reported
      by various centers in large cohorts of patients. However, all of these had
      extensive experience in this special field of radiotherapy and the therepy and
      the follow-up time is too short for definite conclusions. The fact that this
      option of treatment can be carried out on an outpatient basis and that it allows
      to get the patient back to normal as far as social environment and work are
      concerned, has led to wide acceptance of this particular mode of therapy.
      Therefore, permanent seed implantation is a possible treatment option for
      localized prostate cancer and can be  offered to patients with T1- T2a  tumors,
      PSA levels of < 10 and a Gleason score of < 7. By using permanent seed
      implantation in these selected patients, it seems possible to achieve results
      comparable with surgery alone or  percutaneous, 3D-planned radiotherapy.

PMID- 11842749
TI  - Interstitial hyperthermia using thermoseeds in combination with conformal
      radiotherapy for localized prostate cancer.

PMID- 11842750
TI  - High-dose rate brachytherapy--the Charite experience.

PMID- 11842752
TI  - Inverse planning and intensity-modulated radiotherapy in patients with prostate
      cancer.
AB  - Inverse planning and IMRT are methods with the potential to improve substantially
      clinical results in radiotherapy of prostate cancer. Available early clinical
      data demonstrate the feasibility and safety of high-dose IMRT for patients with
      localized prostate cancer and provide a proof-of-principle that this method
      improves dose conformality relative to tumor coverage and exposure to normal
      tissues.

PMID- 11842751
TI  - Anatomy-related and transrectal sonography-guided interstitial high-dose rate
      brachytherapy combined with elective irradiation of the pelvic lymphatics for
      localized prostate cancer: the Kiel experience.

PMID- 11842753
TI  - Radiotherapy after radical prostatectomy in patients with prostate-specific
      antigen elevation.

PMID- 11842754
TI  - Is radiotherapy of pelvic lymph nodes successful in prostate cancer?

PMID- 11842755
TI  - Hormone therapy in advanced prostate cancer.

PMID- 11842756
TI  - Intermittent androgen ablation as a treatment for prostate cancer.

PMID- 11842758
TI  - Adjuvant hormone therapy in locally advanced and localized prostate cancer: three
      EORTC trials.

PMID- 11842757
TI  - Controversies in chemotherapy of prostate cancer.

PMID- 11842759
TI  - Neoadjuvant androgen suppression and external beam radiation therapy.

PMID- 11842760
TI  - Quality of life following radical prostatectomy.

PMID- 11842761
TI  - OR directors share their advice for surviving a building project.

PMID- 11842762
TI  - Tissue banking: industry grows but federal regulation lagging.

PMID- 11842763
TI  - Key decisions in designing a new OR.

PMID- 11842764
TI  - Advice on preanesthesia evaluation.

PMID- 11842765
TI  - New guidelines on postanesthesia care.

PMID- 11842766
TI  - A new look at the OR substerile area.

PMID- 11842767
TI  - How must we secure anesthesia drugs?

PMID- 11842768
TI  - Surgery centers do away with PACUs.

PMID- 11842769
TI  - CDC reports five knee allograft infections.

PMID- 11842770
TI  - Nursing where the food comes from the sky.

PMID- 11842772
TI  - Expanding the role: nurses in general practice.

PMID- 11842771
TI  - Palliative care ethics: autonomy in aged care.

PMID- 11842773
TI  - Research identifies perioperative trauma.

PMID- 11842775
TI  - Nurses say health & safety concerns play major role in employment decisions.

PMID- 11842774
TI  - ASNA home study CE program. What is my responsibility?

PMID- 11842776
TI  - Specifications for an industrial nursing job.

PMID- 11842777
TI  - Defining the roles and functions of occupational and environmental health nurses.
      Results of a national job analysis.
AB  - 1. Effective occupational health nursing practice requires expertise in the
      occupational and environmental health sciences, knowledge of principles of
      business and management, and an understanding of regulatory processes. 2.
      Certification is an effective mechanism for occupational health nurses to
      demonstrate their mastery of knowledge. The validity of the certification
      examination is established through the completion of a job analysis, a systematic
      process that provides a means to describe the various elements of a job including
      the duties and tasks, responsibilities, worker characteristics, and working
      conditions. 3. The job analysis conducted for this study found that respondents
      who were Certified Occupational Health Nurses are more likely to practice in the
      clinician role and those who were Certified Occupational Health Nurse-Specialists
      were more likely to practice in the educator and management role. 4. Because of
      the dynamic and multidimensional nature of occupational health nursing practice,
      it is essential that job analyses be conducted on a regular basis to ensure the
      validity of the certification examination.

PMID- 11842778
TI  - The UAW-GM health promotion program. Successful outcomes.
AB  - 1. The success of the LifeSteps program may rest in the UAW and GM leadership's
      vision to use a high level joint steering committee, a day to day working
      committee, third party program providers, support of confidentiality throughout
      the entire program, and a comprehensive data driven decision making system. 2.
      The program design is a multiplatform method of program delivery to a diverse and
      nationwide population of the active and retired employees and dependents (more
      than 1 million individuals older than age 18). They receive an annual health risk
      appraisal, telephone access to a registered nurse 24 hours a day. LifeSteps
      website, a quarterly health information newsletter and a health care book sent to
      each of the households, and access to a telephonic audiotape library. 3. A pilot
      program has a more intense design of low risk maintenance and high risk reduction
      programs specifically for all active employees who work in the pilot locations. A
      telephonic program for behavior change is available only to high risk individuals
      in the total pilot population of active and retired employees and dependents. 4.
      The major success criterion for the LifeSteps program is helping workers, former
      employees, and their families maintain or achieve low risk status. The increased
      number of employees at low risk status (4% gain the second year and a 2% gain
      from the second to the third year) documents the improved health status of the
      population. Moreover, of surveyed participants and nonparticipants, 85% supported
      program continuation and 74% said they had an improved opinion of the UAW and GM
      due to the program.

PMID- 11842779
TI  - Cervical cancer screening in the workplace. Research review and evaluation.
AB  - 1. The workplace has become an increasingly important site for disseminating
      health information and implementing health promotion activities, including cancer
      screening. 2. Few studies have focused on the benefits and effectiveness of
      worksite programs for Pap tests. 3. It is unclear from studies conducted to date
      if cervical cancer screening in the workplace is more likely to prevent cervical
      cancer than alternative approaches outside the workplace. 4. The occupational and
      environmental health nurse has an important role to play in worksite cancer
      screening programs.

PMID- 11842780
TI  - Resolving ethical dilemas. Applying the institute for Global Ethics' Ethical
      Fitness model to occupational and environmental health practice issues.
AB  - 1. Technological advancements have rapidly increased the need for careful ethical
      choices to preserve life and environment of the global community. 2. No formula
      exists to resolve ethical dilemmas, but using an ethical decision making model
      can help maintain a state of ethical fitness. 3. The Ethical Fitness model relies
      on the assumption that certain core values are universal. Maintaining ethical
      fitness is essential to resolve ethical dilemmas. 4. The process of resolving
      ethical dilemmas consists of analyzing the dilemma using nine checkpoints, four
      dilemma paradigms, and three resolution principles.

PMID- 11842781
TI  - "The strangulation theory" a strangled concept.

PMID- 11842782
TI  - [Cessation of fluoridation of drinking water; results of caries research in Tiel
      and Culemborg in the period of 1968-1988].
AB  - In December 1973 water fluoridation was discontinued in Tiel, the Netherlands.
      Six years later an epidemiological study was started, with the aim to investigate
      the consequences. In the period from 1979 to 1988 a yearly caries investigation
      was carried out in 15 year old children born and living in Tiel and children
      living in the control town of Culemborg, where the drinking water had never been
      fluoridated. The 15 year old children in 1979-1980 in Tiel had a 18% higher
      caries experience than the same age group in 1968-1969, to whom fluoridated water
      had been available from birth onward. In the same period a 28% decrease of the
      caries was found in Culemborg. In 1979-1980 the DMFS-index in Tiel was still 36%
      lower than in Culemborg. Between 1979-1980 and 1987-1988 the caries experience
      decreased in both towns.

PMID- 11842783
TI  - [Dental survey. Part XV. Dental visits 2: motivation and practice].
AB  - This paper is part of a series on the national oral health survey in the
      Netherlands (LEOT-project). In a previous article the results on dental
      attendance (as far as behavior and knowledge are concerned) were described. This
      paper presents the results concerning the other determinants of the dental
      attendance behavior of the dentate Dutch population. The dentate Dutch is
      reasonably content with the dentists behavior. About 10% however, requires more
      information. Anxiety remains for about 55% a negative aspect of dental visits; in
      10% of the cases this leads to postponement of the visits.

PMID- 11842784
TI  - [Adaptation capacity of elderly to new (or improved) dentures; use of a geriatric
      assessment subscale].
AB  - Elderly people's diminished adaptability is an important factor in their
      acceptance of new or improved dentures. This research project shows that a
      geriatric rating scale for infirmity may have a valuable predictive function for
      adaptability.

PMID- 11842785
TI  - Antiretroviral therapy is only part of it.

PMID- 11842786
TI  - HAART--the need for strategically focused investments.

PMID- 11842787
TI  - AIDS care is learnt by doing it.

PMID- 11842788
TI  - HAART in Haiti--evidence needed.

PMID- 11842789
TI  - Ectopic IUD complicating pregnancy. A case report.
AB  - BACKGROUND: For the most part, intrauterine devices (IUDs) have a low
      complication rate and minimal side effects. However, one of the most common
      reasons for contraceptive failure while using an IUD is its translocation or
      extrauterine migration. Pregnancy complicated by translocation or an ectopic IUD
      can present a formidable clinical challenge. CASE: A 23-year-old woman, gravida
      3, para 2, using a copper-7 IUD for contraception, presented at 7 weeks'
      gestation. Transvaginal sonogram confirmed the presence of a fetal pole with
      cardiac activity; however, the IUD was not detectable. An anteroposterior
      roentgenogram showed 90 degrees counterclockwise rotation of the IUD relative to
      the normal position. Laparoscopy was performed at 14 weeks. The IUD was
      extrauterine, buried in omental adhesions attached to the anterior abdominal
      wall. The IUD was dissected free and removed without difficulty. The remainder of
      the pregnancy was uncomplicated. CONCLUSION: Uterine perforation is a recognized
      and potentially hazardous complication of IUD use. Localization of a lost IUD
      should follow an organized and systematic approach utilizing an assortment of
      radiologic and operative techniques. We report the third known case utilizing
      laparoscopy to remove an ectopic IUD complicating early pregnancy. Laparoscopy,
      even during pregnancy, has proven to be a safe and simple tool for managing a
      variety of surgical conditions.

PMID- 11842791
TI  - Health costs rise 13% in 2002.

PMID- 11842790
TI  - California launches drug rebate program for elderly and disabled.

PMID- 11842792
TI  - BCBC tries an unusual disease care plan.

PMID- 11842793
TI  - High use of certain drug classes driving costs in Medicaid managed care plans.

PMID- 11842794
TI  - Michigan sets medication restrictions.

PMID- 11842796
TI  - Terrorist activity pushes health care costs higher.

PMID- 11842795
TI  - Rx prices projected to increase 20% in 2002.

PMID- 11842797
TI  - Insurers brace for 9/11/01 disability claims.

PMID- 11842798
TI  - New institute focuses on health costs.

PMID- 11842799
TI  - [Abundant hemorrhage in the ear after tympanostomy].

PMID- 11842800
TI  - 166mHo: a multi-gamma standard for the calibration of Ge spectrometers.
AB  - Efficiency calibration curves for germanium detectors are usually established by
      using a large number of standard gamma-ray sources of specific radionuclides,
      that decay with few gamma-rays, or radionuclides with complex decay schemes, such
      as 133Ba or 152Eu. But these multi-gamma radionuclides cannot be used alone,
      because the gamma-rays of high intensity are irregularly distributed across the
      energy spectrum. 166mHo is a more suitable single source for such calibrations,
      because this radionuclide decays by beta(-)emission to the excited states of
      166Er with the subsequent emission of about 20 strong and well distributed gamma
      rays ever the energy range 50-1000 keV. Moreover, with a relatively long half
      life (1200 yr) and characteristic X-rays between 40 and 50 keV, this nuclide is a
      good standard for the calibration of germanium detectors. The X- and gamma-ray
      emission probabilities of their main lines need to be known with good accuracy in
      order to resolve the discrepancies found in the literature. A combination of 4pi
      beta-gamma coincidence and X- and gamma-ray spectrometric techniques have been
      used to determine 50 photon emission probabilities.

PMID- 11842801
TI  - Radioactivity standardization in South Africa.
AB  - South Africa's national radioactivity measurement standard is maintained at a
      satellite laboratory in Cape Town by the National Metrology Laboratory (NML) of
      the Council for Scientific and Industrial Research. Standardizations are
      undertaken by a number of direct methods utilizing liquid scintillation counting
      (LSC). The successful application of LSC to the 4pi beta-gamma coincidence method
      is reviewed. The activity unit is maintained through radionuclide specific
      calibration factors relating to a pressurized re-entrant well type ionization
      chamber. A comparison is made between normalized factors given by the
      manufacturer and deduced factors obtained by a method used to transfer
      calibration factors from the International Reference System of the International
      Bureau of Weights and Measures based on the NML's own absolute standardizations.

PMID- 11842802
TI  - Study of inhomogeneities in sources prepared for alpha-particle spectrometry
      using scanning probe microscopy.
AB  - For high-resolution alpha-particle spectrometry, sources of high quality must be
      prepared by methods giving the thinnest and most homogeneous deposit possible on
      a suitable support. Surface characteristics of several types of alpha-particle
      sources were studied using a scanning probe microscope. Major inhomogeneities
      were observed, which means that the materials and techniques used for thc
      preparation of sources must be improved.

PMID- 11842803
TI  - Performance of dose calibrators in Brazilian hospitals for activity measurements.
AB  - In order to obtain information on the accuracy of activity measurements in
      Brazilian hospitals, several intercomparison exercises have been organized since
      1998. The first exercise consisted of two intercomparison runs of 131I and 99mTc
      and had the participation of 21 hospitals localized in Rio de Janeiro city and
      surroundings. The second, with 131I (47 hospitals) and 123I (12 hospitals), had
      the participation of hospitals localized in the whole country. The results were
      analyzed under the statistical point of view and conformity to the norms of
      Regulatory Authority. These results have shown that such exercises are necessary
      to improve the quality of the measurements and to identify those instruments that
      are producing incorrect values.

PMID- 11842804
TI  - NIST radiochemistry intercomparison program: a summary of four-year performance
      evaluation study. National Institute of Standards and Technology.
AB  - This paper summarizes the methods currently applied by the National Institute of
      Standards and Technology (NIST) for the preparation and verification of
      environmental and radiobioaasay performance evaluation materials for the
      traceability testing of low-level radioactivity measurements. The evaluation of
      measurement quality of the all participants indicated that over 90% of the
      intercomparison results complied with ANSI N42.22 and/or HPS N13.30 standards.
      Overall, the differences from the NIST values observed for all test nuclides and
      matrices are less than -7%, with a typical measurement precision better than 10%
      (1 s). The dependency of measurement quality on the test radionuclides, sample
      matrices, and radiochemical methods is identified by statistical analyses.

PMID- 11842805
TI  - Study of the representativity of uranium and thorium assays in soil and sediment
      samples by alpha spectrometry.
AB  - The activity concentrations of soil and sediment samples are determined by alpha
      spectrometry with a sample size usually < 1 g. Hence, a systematic and careful
      procedure must be followed in the sampling and pre-treatment of the sample in
      order to ensure that the aliquot analysed represents the activity concentration
      of the entire sample. Statistical analyses of the activity concentrations of
      uranium and thorium isotopes in soil and sediment samples were performed to study
      the activity variation due to the lack of the representativity of the sample.
      These studies showed that, although some uncertainty in the determination of the
      sample activity concentration may be due to the lack of representativity (about
      10%), the procedure followed for the pre-treatment of the sample can be
      considered adequate, providing an acceptable level of representativity.

PMID- 11842806
TI  - Metrological capability of the Brazilian laboratories of analyses of
      radionuclides in environmental samples.
AB  - The metrological capability of 24 Brazilian laboratories of radionuclide
      determinations in environmental samples was analysed for purposes to establish
      requirements for accreditation of laboratory for each radionuclide. For each type
      of analysis, the range of activity per unit mass or volume, the range of the
      reference value and its correspondent uncertainty were described. The accuracy
      was established using the statistical criteria of USE.P.A. for the laboratory
      performance classification. The precision of the analyses, expressed by its
      variation coefficient of the laboratory determinations, was classified in
      intervals of 5%. The data base was constituted by 3013 results of analyses
      obtained in 28 intercomparison runs performed from 1991 to 2000, for K, Th, Unat,
      gross alpha, gross beta, and other 27 radionuclides, in matrices of water, soil,
      vegetation, air filter and milk. The quality criteria established were the
      variation coefficient less than 5% and good performance in intercomparison runs.
      Results included from 5% to 10% are also considered, for special types of
      matrices and radionuclides.

PMID- 11842807
TI  - Standardization of a 89Sr solution from a BIPM intercomparison using a liquid
      scintillation method.
AB  - A procedure to standardize 89Sr (as strontium chloride) solutions, within the
      frame of a BIPM intercomparison, by the CIEMAT/NIST method was presented for
      Instagel Plus, HiSafe III and Ultima Gold liquid scintillation cocktails. The
      stability was studied for two types of samples: those obtained by direct addition
      of the 89Sr solution and those by the extra addition of 0.5 ml of HCl (0.1 mol l(
      1)) to the cocktails. The results only showed good stability with the three
      scintillants used when additional HCl was added to the cocktails. The activities
      per unit mass determined for 89Sr were: 26.344 kBq g(-1) for Instagel Plus;
      26.335 kBq g(-1) for HiSafe III; and 26.310 kBq g(-1) for Ultima Gold (at a
      reference time of 2000.10.01, 00 h UT) with a total uncertainty of 0.5% in each
      case (k = 1).

PMID- 11842808
TI  - The effect of energy losses in alpha-particle sources on the shape of peaks in
      spectra obtained with wide-angle geometry.
AB  - It has been shown that two main effects contribute to the tailing in the shapes
      of alpha-peaks measured with silicon detectors: the ionization loss in the source
      and the response of the detector. We studied the relative influence of both
      factors in measurements with small source-to-detector distances. The computer
      simulation code 'the stopping and range of ions in matter' has been used to
      obtain the energy spectra of a 226Ra source as a function of the source
      thickness. Results of the simulation are compared with experimental measurements.

PMID- 11842809
TI  - Competence of alpha spectrometry analysis algorithms used to resolve the 241Am
      and 243Am alpha peak overlap.
AB  - Five alpha spectrometry analysis algorithms were evaluated for their ability to
      resolve the 241Am and 243Am peak overlap present under typical low-level counting
      conditions. The major factors affecting the performance of the algorithms were
      identified using design-of-experiment combined with statistical analysis of the
      results. The study showed that the accuracy of the 241Am/243Am ratios calculated
      by the algorithms depends greatly on the degree of peak deformation and tailing.
      Despite the improved data quality obtained using an algorithm that may include
      peak addition and tail estimation, the accurate determination of 241Am by alpha
      spectrometry relies primarily on reduction of peak overlap rather than on
      algorithm selection.

PMID- 11842811
TI  - A tribute to Nikola Tesla.

PMID- 11842810
TI  - Traumatic false aneurysm in the popliteal artery of a child.

PMID- 11842812
TI  - JAMA patient page. Heart failure.

PMID- 11842814
TI  - Collection of airborne fluorinated organics and analysis by gas
      chromatography/chemical ionization mass spectrometry.
AB  - The ubiquitous detection of perfluorooctane sulfonate (PFOS) in humans and
      animals has produced a need for sensitive and compound-specific analytical
      methods to determine the environmental distribution of fluorinated organic
      contaminants. A suite of potential PFOS precursors (sulfonamides) and
      fluorotelomer alcohols (FTOHs) were separated by gas chromatography and detected
      by chemical ionization mass spectrometry (GC/CI-MS). Full-scan spectra were
      collected in both positive and negative chemical ionization (PCI and NCI,
      respectively) mode to determine retention time windows and fragmentation
      patterns. In selected ion monitoring (SIM) mode, instrumental detection limits
      ranged from 0.2 to 20 pg for individual analytes, depending on ionization mode.
      PCI mode was preferred for routine analysis because of the simple mass spectra
      produced, typified by the presence of a major molecular ion [M + H]+. High-volume
      air samplers collected gaseous and particle-bound fluoroorganics on composite
      media consisting of XAD-2, polyurethane foam (PUF), and quartz-fiber filters. The
      combined collection efficiency for individual analytes was 87 to 136% in
      breakthrough experiments. Application of the method to the analysis of ambient
      air from urban and rural sites confirmed the presence of six novel fluorinated
      atmospheric contaminants at picogram per meter3 concentrations. Low
      concentrations of fluoroorganics were consistently detected in blanks (<4 pg m(
      3)); however, this did not prevent confirmation or quantification of
      environmental concentrations.

PMID- 11842815
TI  - Polymorphism of the CTLA-4 gene is associated with autoimmune hypothyroidism in
      the United Kingdom.
AB  - The cytotoxic T-lymphocyte-associated-4 (CTLA-4) molecule plays an important role
      in immune regulation by downregulating activation of T cells by antigen
      presenting cells. Polymorphisms of the CTLA-4 gene have been shown to be
      associated with susceptibility to a number of autoimmune diseases. Some, but not
      all, studies suggest association between the CTLA-4 gene and autoimmune
      hypothyroidism. The aim of this study was to determine whether allelic
      association was present between the A-G single nucleotide polymorphism (SNP) at
      position 49 in exon 1 of the CTLA-4 gene and autoimmune hypothyroidism. The study
      was performed in 158 patients with autoimmune hypothyroidism and 384 control
      subjects. All subjects were white Caucasians from the United Kingdom. Genotyping
      was carried out by polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP) using the restriction enzyme Bbv1. There was a
      significant excess of the G allele in patients with autoimmune hypothyroidism
      compared with controls (43% vs. 32% respectively; chi2 = 10.7, p = 0.001; odds
      ratio 1.57). The GG and the AG genotypes were found to be more frequent in
      patients with autoimmune hypothyroidism than controls (17% vs. 8.8% and 50% vs.
      46% respectively; chi2 = 11.7, p = 0.003). These results suggest that the CTLA-4
      gene region on chromosome 2q33 is a susceptibility locus for autoimmune
      hypothyroidism in the United Kingdom.

PMID- 11842813
TI  - The novel BLM3 gene encodes a protein that protects against lethal effects of
      oxidative damage.
AB  - Mutational alteration of the BLM3 gene in Saccharomyces cerevisiae confers
      hypersensitivities to lethal effects of ionizing radiation, anticancer bleomycins
      and structurally-related phleomycins. Bleomycin is used clinically in the
      treatment of many types of cancers, including Kaposi's sarcoma. The BLM3 gene was
      cloned from a genomic library by complementing the drug hypersensitivities
      conferred by the codominant blm3-1 mutation. The nucleotide sequence of BLM3
      encodes a predicted integral protein of 1804 amino acids with seven to ten
      potential transmembrane domains and additional motifs. The blm3 null mutation was
      created by gene replacement, and found not to be essential for growth in the
      absence of the bleomycin-phleomycin antibiotics. Sequence analyses suggest the
      Blm3p could be a potential member of the major facilitator superfamily (MFS) of
      permeases. Northern dot blot analyses using a human RNA master tissue blot
      containing RNA from fifty different fetal and adult tissues revealed sequence
      homology in adult tissues to BLM3, but no sequence homology in fetal tissues. The
      function of the Blm3p is presently unknown. We propose several functions for the
      Blm3p in protecting cells against oxidative agents, including roles in
      detoxification, transport and defending against DNA damage.

PMID- 11842816
TI  - Epidemiology and control of an outbreak of classical swine fever in wild boar in
      Switzerland.
AB  - An outbreak of classical swine fever in wild boar in the southern part of
      Switzerland (Canton of Ticino) was investigated after the implementation of
      control measures in a defined infected area (the risk zone), and in a surrounding
      surveillance zone (the non-risk zone). After the disease had been detected,
      hunting was not allowed in the risk zone for over six months, during which the
      disease was left to run its course, but hunting was continued in the non-risk
      zone for one month. After seven months, a hunting strategy targeted at young
      animals was implemented in both zones. Between May 1998 and January 2000,1294
      wild boar were shot or found dead, and diagnostic and biological data were
      collected and analysed. Only one animal from the non-risk zone was found to be
      seropositive for antibodies to the virus, whereas 179 of 528 wild boar from the
      risk zone were virus positive and 162 were seropositive. The proportion of virus
      positive animals decreased from 62.7 per cent to zero over one year. During the
      first hunting season, seropositive animals were found in all age groups, but 12
      months later only animals more than one year old had antibodies against the
      virus.

PMID- 11842817
TI  - Mycoplasmas affecting the eyes of poultry.

PMID- 11842818
TI  - Evaluation of peripheral lymphoreticular biopsy techniques and their clinical
      side effects in sheep.
AB  - Tissue samples were collected postmortem from 126 sheep at five lymphoreticular
      sites by different techniques. The three most successful combinations of sites
      and techniques were: the third eyelids, using a forceps and scissors, which
      provided a mean (se) of 5.32 (0.70) lymphoid follicles per 5 microm tissue
      section, a mandibular lymph node, using a Biopty gun, which gave 1.19 (0.26)
      lymphoid follicles per 5 microm tissue section, and tonsil, using a biopsy
      forceps, which gave 1.14 (0.27) lymphoid follicles per 5 microm tissue section.
      These three techniques were repeated once a month for five months on five sheep
      under general anaesthesia, and their clinical effects were compared with five
      control sheep which were restrained and anaesthetised in the same way but from
      which no biopsies were taken. Most lymphoid follicles (3.47 [0.58] per 5 pm
      tissue section) were obtained by using the third eyelid biopsy technique. There
      were no clinical side effects associated with the biopsy procedure. There were
      increases in the plasma concentration of cortisol in all the animals, suggesting
      that the restraint and anaesthesia were more stressful than the biopsy procedure.

PMID- 11842819
TI  - A practical approach to and long-term results of fitting silicone contact lenses
      in aphakic children after congenital cataract.
AB  - PURPOSE: This prospective study investigated characteristics of fit and
      performance of silicone contact lenses under conditions of permanent wear in
      cases of aphakia after congenital cataract. METHODS: Seventeen aphakic children
      (8 eyes unilateral, 18 eyes bilateral) were fitted with silicone contact lenses
      on an empirical basis without the use of keratometry. The lenses were worn on a
      permanent basis, with a routine replacement every 3 months. The follow up was 6
      years, with evaluation lens parameters, fitting characteristics, lens condition,
      replacement rate, wearing time, complications, and visual acuity. RESULTS: The
      back optical zone radius (BOZR) remained stable at 7.50 mm, up to the age of 1.5
      years old. At the age of 4 years, almost all eyes needed a BOZR of 7.90 mm. Mean
      +/- SD contact lens power was +25.47 diopter (D) +/- 4.0 (range +32.00 D - +20.00
      D) at 3 months of age, and +17.94 D +/- 3.8 (range +29.00 D - +15.00 D) at 3
      years of age. This represents an average decrease of 0.23 D per month. The power
      decrease in unilateral cases was significantly lower (P < 0.01) than in bilateral
      aphakia. Snellen visual acuity at 4 years of age was 0.1 to 0.3 (20/200-20/60) in
      15 eyes, 0.3 to 0.5 (20/60-20/40) in 10 eyes and greater than 0.5 (>20/40) in 1
      eye. Lens usage over a total period of 90 wearing years was 5.6 lenses/eye/year,
      including the regular exchange every 3 months. No serious complications occurred.
      A positive correlation (r = 0.89) was found between age and deposit buildup. With
      the need for permanent wear reduced, therefore, 73% of the eyes were refitted
      with high-water content soft lenses or high gas-permeable (HGP) lenses, when the
      patients ranged in age from 4 to 6 years old. CONCLUSIONS: The procedure for
      fitting silicone lenses in aphakic children is feasible in an easy and logical
      way without keratometry. Permanent wear with a low complication rate is possible
      up to the age of 3. with a lens usage (including a 3-month regular exchange) of
      5.6 lenses/eye/year. From the age of 3, deposit formation is the determining
      factor for refitting with high-water content soft or HGP lenses.

PMID- 11842820
TI  - Health belief and health practice in contact lens wear--a dichotomy?
AB  - PURPOSE: To establish if the hygiene practice of contact lens wearers (CLWs) can
      be influenced by "health belief." METHODS: A nested case-control study based on
      questionnaires was conducted in Hong Kong over a 17-month period between 45 CLW
      patients with microbial keratitis and 135 matched asymptomatic CLW volunteer
      controls. RESULTS: There was no significant difference between keratitis patients
      and controls (volunteers) in the perceived benefits of optometrists' instructions
      generally. When asked specifically, however, keratitis patients scored
      significantly higher than controls in the perceived benefit of checking initially
      with the optometrist for the correct method of lens cleaning. Contact lens
      wearing patients with keratitis were confident that their care of lenses would
      prevent complications, but this probably represented over confidence in
      themselves. Patients also scored significantly more neutrally in self-efficacy.
      Surprisingly, patients were significantly less likely to perceive the cost of
      lens care as a barrier but did not use their disinfecting regimes properly.
      CONCLUSION: We have found that CLWs still regard their eye care professional as
      being the most important for giving them advice on hygiene. There is considerable
      opportunity to educate and influence CLWs in ways to prevent infection, but the
      advice given must be correct. Continuing education of optometrists is also
      required.

PMID- 11842821
TI  - Functional disability in relation to radiological damage and disease activity in
      patients with rheumatoid arthritis in remission.
AB  - OBJECTIVE: To investigate the relationship between functional disability, disease
      activity and radiological damage in patients with rheumatoid arthritis (RA) in
      remission. METHODS: One hundred and eighty-six patients with RA in remission or
      with low disease activity were studied. The following variables were assessed at
      one time point: joint count, visual analog scale for pain, functional disability,
      i.e., health assessment questionnaire (HAQ) score, radiological joint damage as
      assessed by radiographs of hands and feet and scored according the Sharp-van der
      Heijde method, and presence of comorbidity. Disease activity was expressed as the
      disease activity score (DAS). Correlations were calculated by Spearman's rho
      coefficient of correlation. In addition, variables associated with the score were
      analyzed by logistic regression. RESULTS: The median HAQ score was 0.25
      [interquartile (IQR) range 0-0.75] and the median DAS was 1.0 (IQR 0.7-1.5). Of
      the 186 RA patients included, 82% were in remission according to the DAS. The
      median joint damage as assessed by the Sharp-van der Heijde score was 21 (IQR 9
      74). Functional disability was significantly correlated with pain (rho 0.48, p <
      0.001), disease activity (rho 0.42; p < 0.001), disease duration (rho 0.39; p <
      0.001), radiographic joint damage (rho 0.37; p < 0.001), and age (rho 0.19; p =
      0.01). In a logistic regression model functional disability was independently
      related to presence of pain, disease activity, radiographic joint damage and
      disease duration in decreasing order of strength, but not to age. sex and co
      morbidity. CONCLUSION: Patients with RA who are in remission might experience
      minimal functional disability and radiographic joint damage. Functional
      disability in RA patients in remission is most strongly related to the presence
      of pain and in lesser extent to disease activity, radiographic joint damage, and
      disease duration.

PMID- 11842822
TI  - Patients chosen for treatment with cyclosporine because of severe rheumatoid
      arthritis are more likely to carry HLA-DRB1 shared epitope alleles, and have
      earlier disease onset.
AB  - OBJECTIVE: To determine whether patients with rheumatoid arthritis (RA) selected
      for treatment with cyclosporin A (CSA) because of severe disease are more likely
      to carry HLA-DRB1 alleles encoding the conserved "shared epitope" (SE) sequence.
      METHODS: The majority of patients (n = 178) were currently being treated with
      methotrexate (MTX), either alone or in combination with chloroquine and/or CSA.
      In about 30% of patients, treatment with CSA had been initiated because of
      limited response to MTX or MTX and chloroquine. Patients were treated as
      clinically indicated without knowledge of their HLA-DRB1 status. HLA-DRB1 typing
      was by a reverse dot blot method. RESULTS: Patients that had been treated with
      CSA were significantly more likely to carry an SE allele than patients not
      treated with CSA (81.5% vs 60.5%; OR 2.9, p = 0.006). Patients with 2 SE alleles
      were the most likely to have been treated with CSA. Results were still
      significant after correction for age, sex, and disease duration in a logistic
      regression model. There was no association between rheumatoid factor positivity
      and requirement for CSA therapy. Examination of individual SE alleles by multiple
      logistic regression analysis indicated that the strongest association was with
      presence of HLA-DRB1**0401 (p = 0.004). The DRB1*0401/*0404 genotype provided the
      greatest risk of requiring CSA treatment. Patients selected for CSA treatment had
      developed RA at a significantly earlier age than those not requiring CSA (44.4 vs
      51.3 yrs; p = 0.004). CONCLUSION: Patients requiring treatment with CSA because
      of severe RA were significantly more likely to carry an SE allele than patients
      not requiring such treatment. CSA treated patients were also more likely to have
      had earlier age of disease onset. These data provide further evidence that
      bearing the SE (particularly 2 alleles) is associated with development of severe
      RA.

PMID- 11842824
TI  - Cyclophosphamide with low or high dose prednisolone for systemic sclerosis lung
      disease.
AB  - OBJECTIVE: To evaluate the safety and efficacy of monthly intravenous pulses of
      cyclophosphamide (CP) in combination with low or high doses of prednisolone in
      patients with systemic sclerosis (SSc) related interstitial lung disease (ILD)
      with FVC < 70% of predicted. METHODS: An open label, non-parallel arm study,
      performed in the rheumatology outpatient clinic of a university hospital. Twenty
      eight patients with SSc related ILD were evaluated. Endpoint evaluations included
      the evolution of high resolution computed tomography, pulmonary function tests,
      skin involvement and dyspnea over 12 months. Patients were treated with monthly
      IV CP in combination with prednisolone at low (< 10 mg/day; n = 12) or high doses
      (1 mg/kg/day for 4 weeks, then reducing the prednisolone by 5 mg/day on
      alternating days each 2 weeks; n = 16). RESULTS: In the low dose steroid group,
      no improvement was seen for any endpoint at 6 and 12 months of followup. In the
      high dose steroid group, at 12 months there was significant improvement in the
      percentage of "ground glass" parenchymal lung involvement (-5.7%; p = 0.003), as
      well as in the percentage of predicted FVC (12.4%; p < 0.001), the percentage of
      predicted DLCO (7.3%; p = 0.029), the percentage of skin involvement (-5.4%; p =
      0.01), and the severity of dyspnea (p = 0.012). Substantial improvement was seen
      as early as 6 months. One patient (low dose group) died from ILD. CONCLUSION: A
      combination of IV pulse CP with high doses of prednisolone shows promising
      efficacy in improving the clinical, physiological, and radiological evolution of
      SSc related ILD with reversal of the underlying alveolitis.

PMID- 11842825
TI  - Peak oxygen uptake and ventilatory anaerobic threshold in fibromyalgia.
AB  - OBJECTIVE: To compare maximum oxygen uptake and anaerobic threshold in patients
      with fibromyalgia (FM) and healthy sedentary controls matched by sex, age,
      weight, and body mass index. METHODS: Fifty women with FM aged 18-60 years and 50
      healthy sedentary controls were studied. All were submitted to a maximum
      treadmill incremental test. Expired gas, ventilatory anaerobic threshold, and
      maximum oxygen uptake (VO2max) were evaluated. The influence of FM on quality of
      life was evaluated by questionnaires: the Fibromyalgia Impact Questionnaire and
      the Medical Outcomes Study Short-Form (SF-36). RESULTS: In patients with FM, the
      anaerobic threshold and peak oxygen uptake were significantly reduced. Maximum
      heartbeat rate was significantly lower in FM, indicating submaximum effort.
      Linear regression data showed a correlation between peak VO2 and the "Role
      physical" domain of the SF-36. No such correlations were noted with anaerobic
      threshold. CONCLUSION: These results confirm the hypothesis of lower physical
      fitness in patients with FM. Considering that patients with FM do not achieve a
      maximum effort, ventilatory anaerobic threshold should be considered as a better
      fitness index than VO2max.

PMID- 11842826
TI  - Automatic fusion of freehand endoscopic brain images to three-dimensional
      surfaces: creating stereoscopic panoramas.
AB  - A major limitation of the use of endoscopes in minimally invasive surgery is the
      lack of relative context between the endoscope and its surroundings. The purpose
      of this work was to fuse images obtained from a tracked endoscope to surfaces
      derived from three-dimensional (3-D) preoperative magnetic resonance or computed
      tomography (CT) data, for assistance in surgical planning, training and guidance.
      We extracted polygonal surfaces from preoperative CT images of a standard brain
      phantom and digitized endoscopic video images from a tracked neuro-endoscope. The
      optical properties of the endoscope were characterized using a simple calibration
      procedure. Registration of the phantom (physical space) and CT images
      (preoperative image space) was accomplished using fiducial markers that could be
      identified both on the phantom and within the images. The endoscopic images were
      corrected for radial lens distortion and then mapped onto the extracted surfaces
      via a two-dimensional 2-D to 3-D mapping algorithm. The optical tracker has an
      accuracy of about 0.3 mm at its centroid, which allows the endoscope tip to be
      localized to within 1.0 mm. The mapping operation allows multiple endoscopic
      images to be "painted" onto the 3-D brain surfaces, as they are acquired, in the
      correct anatomical position. This allows panoramic and stereoscopic
      visualization, as well as navigation of the 3-D surface, painted with multiple
      endoscopic views, from arbitrary perspectives.

PMID- 11842823
TI  - Brachial endothelial function is impaired in patients with systemic lupus
      erythematosus.
AB  - OBJECTIVE: To verify if endothelial function is impaired in pre-menopausal women
      with systemic lupus erythematosus (SLE) and whether endothelial dysfunction is
      related to disease duration, cumulative prednisone dose, antimalarial use,
      anticardiolipin antibody (aCL), hypertension, Raynaud's phenomenon, disease
      activity score, and vasculitis. METHODS: Using high-resolution ultrasound, we
      measured the diameter of brachial artery at rest, during reactive hyperemia, and
      after glyceryl trinitrate (GTN). We compared 69 pre-menopausal female patients
      with SLE (mean age 29 +/- 8 years) with 35 age and sex-matched controls (mean age
      29 +/- 6 years), The mean disease duration was 72 months. RESULTS: There was no
      significant difference in baseline brachial artery diameter. The flow-mediated
      dilation (endothelial dependent dilation) was significantly impaired in SLE
      patients when compared to controls (5.0 +/- 5.0% vs 12.0 +/- 6.0%, p < 0.001),
      even in the subgroup of patients without coronary artery disease risk factor (4.5
      +/- 4.0% vs 12.0 +/- 6.0%, p < 0.001). The GTN induced dilation (endothelial
      independent dilation) was significantly lower in the aCL positive SLE patients
      when compared to the controls (11.9 +/- 4.0% vs 16.3 +/- 6.0%, p < 0.05). The
      endothelium-dependent dilation was not related to disease duration, cumulative
      prednisone dose, antimalarial use, anticardiolipin antibody, hypertension
      history, Raynaud's phenomenon, SLE disease activity score or vasculitis.
      CONCLUSION: This is the first study using brachial artery ultrasound imaging to
      evaluate endothelium function in SLE. Patients with SLE presented lower flow
      mediated dilation (endothelium dependent dilation) than sex and age-matched
      controls, even in patients without traditional cardiovascular risk factors and
      this may represent an early atherosclerotic process.

PMID- 11842828
TI  - Demand increasing for women in gastroenterology.

PMID- 11842827
TI  - Hepatitis B "X" gene linked to cellular calcium release.

PMID- 11842829
TI  - Image of the month. Nodular fatty infiltration of the liver in Wilson's disease.

PMID- 11842830
TI  - Informed consent for the neurosurgeon.
AB  - Obtaining informed consent from patients contemplating neurosurgical procedures
      is an important process in preoperative care. A surgeon's failure to fulfill his
      or her legally prescribed duty to inform the patient and obtain consent can
      result in unnecessary exposure to liability. This paper describes the legal
      background, doctrine, and elements of informed consent. It also outlines the
      dialog that should legally take place between physician and patient before a
      planned procedure and discusses special circumstances that may affect the
      informed consent process.

PMID- 11842831
TI  - Quiz page. IgA nephropathy.

PMID- 11842832
TI  - Fever after coronary artery bypass graft surgery increases likelihood of
      cognitive loss.

PMID- 11842833
TI  - Hormone levels predict congestive heart failure, mortality.

PMID- 11842834
TI  - The American Alliance of TMD Organizations.

PMID- 11842835
TI  - The growth of articular eminence height during craniofacial growth period.
AB  - This study was done to study the growth of the articular eminence height during
      the postnatal craniofacial growth period. Ninety (90) skulls were divided into
      three equal groups, named A, B, and C. The A group belonged to individuals
      showing deciduous dentition, the B group showed mixed dentition, and the C group
      permanent dentition. The skulls were stabilized so that the FH plane was really
      horizontal. This was assured using a common facial bow, inserted into the
      acoustic meatuses and the infraorbital foramen, and a common water-level device.
      Using a silicone type impression material, impressions were taken of all temporal
      fossae. Special care was taken in order that the base of the materials was
      parallel to the FH plane. After setting, the impression was removed and a common
      eggslicer was used to cut the material into sections of 2.5 mm each. The three
      middle sections were removed, photocopied with a common photocopy machine,
      enlarged to a 200% scale and the height of the eminentia were measured by using
      an electronic caliper. The mean of the three calculations was reduced to its
      normal value, and was tabulated for each eminence. The study concluded that the
      articular eminence height grows at a very high rate until the age of seven (the
      period of deciduous dentition, development, and function), almost stops until the
      age of eleven (the period of mixed dentition), and acquires the rest of its
      height by the age of 20. This growth plan more nearly approximates the somatic or
      the general growth curve.

PMID- 11842836
TI  - The effect of four-week administration of amitriptyline on sleep bruxism. A
      double-blind crossover clinical study.
AB  - The purpose of this study was to evaluate the effect of a tricyclic
      antidepressant (amitriptyline) on nocturnal masseteric activity and duration of
      sleep in bruxists. Using a randomized, double blind, crossover design, ten
      females (mean age 39 yrs, +/- sd seven yrs) received active (amitriptyline 25
      mg/night) and inactive (placebo 25 mg/night) medication, over a period of four
      weeks each. A portable EMG integrator recorded the nocturnal, unilateral, and
      cumulative myoelectrical activity (microV/min of sleep) of the masseter muscle
      during the fourth and eighth weeks of the study. The results showed that
      amitriptyline did not significantly decrease the mean EMG activity (df = 9, alpha
      = 0.05, paired-t = 0.892, p = 0.3964), nor did it significantly increase the
      duration of sleep (df = 9, alpha = 0.05, paired-t = 2.140, p = 0.061). The
      results of this study do not support the administration of 25 mg of amitriptyline
      per night over a period of four weeks for the management of sleep bruxism.

PMID- 11842837
TI  - An investigation of the effectiveness of exercise and manual therapy in treating
      symptoms of TMJ osteoarthritis.
AB  - The background and purpose of this investigation was to evaluate the use of a
      treatment protocol which included active and passive jaw movements, manual
      therapy techniques, correction of body posture, and relaxation techniques for the
      treatment of temporomandibular joint (TMJ) osteoarthrosis (OA). Twenty
      consecutive patients suffering from TMJ OA participated in this study. INCLUSION
      CRITERIA: a. pain in the temporomandibular region; b. symptoms lasting at least
      three months; and c. radiologically proven OA. All patients were assigned to a
      waiting list, serving as a no treatment control period. Nineteen patients
      completed the study. No adverse effects occurred. During the control period (mean
      duration 35 days), the parameters did not change significantly. After treatment
      (mean duration 46 days) pain, impairment, and incisal edge clearance improved
      significantly (Wilcoxon test p < 0.001). At follow-up, pain and impairment were
      further reduced. The number of patients experiencing no pain at rest (80%), chi
      square test p = 0.02) and stress (47%), chi-square test p = 0.03), and no
      impairment (37%), chi-square test p = 0.05) increased significantly. This
      therapeutic treatment protocol seems to be useful treatment for the symptoms of
      clinical dysfunction in OA of the TMJ.

PMID- 11842838
TI  - Did the vote destroy us?

PMID- 11842839
TI  - Classic symptoms in temporomandibular disorder patients: a comparative study.
AB  - Numerous symptoms have been reported in the literature associated with
      temporomandibular disorders (TMD). However, it has not been stated what TMD
      symptoms are the most important and consistent and in turn, can be referred to as
      the gold standard or classic symptoms. The purpose of this study was: 1. To
      review the literature regarding TMD symptoms; 2. To compare so-called classic TMD
      symptoms with the symptoms of patients diagnosed as having TMD. Out of 52
      consecutive patients, 40 were diagnosed as having TMD and were selected for this
      study. Forty non-TMD subjects served as a control group. A total range of
      subjective symptoms, from a self-administered TMD history form, was collected,
      but only so-called classic or the most common TMD symptoms were reported in this
      study. Results revealed that the major complaints of the TMD patients, including
      headaches, were similar to the suggested classic TMD symptoms derived from the
      literature.

PMID- 11842840
TI  - Effect of a thick palatal appliance on muscular symptoms in craniomandibular
      disorders: a preliminary study.
AB  - Several treatment modalities for myofascial pain dysfunction syndrome (MPD) are
      being used at present. However, from the standpoint of patients' quality of life,
      it would be reasonable to seek a more effective treatment modality. This study
      aimed to show clinical data of a preliminary study regarding the effect of a
      thick palatal appliance, designed to fill the palatal concavity with a thick
      resin base, on muscular symptoms in eighteen MPD patients. Shown here are the
      clinical results of two volunteer patients using palatal appliances of two
      different thicknesses. In this study, MPD patents were divided into the three
      following groups: 1. no-treatment group; 2. thick palatal appliance group; and 3.
      medication group. Based on the results of this study, it was suggested that the
      thick palatal appliance could bring about early improvement of MPD syndrome. It
      is suggested that the thickness of the palatal plate was an important factor in
      obtaining the clinical effect.

PMID- 11842841
TI  - Anatomically and physiologically based guidelines for use of the sphenopalatine
      ganglion block versus the stellate ganglion block to reduce atypical facial pain.
AB  - This literature review is designed to develop guidelines needed for the use of a
      sphenopalatine ganglion block versus a stellate ganglion block to reduce atypical
      facial pain. We have reviewed the basic anatomy of both ganglia and the
      physiological responses usually associated with each, and have given an opinion
      on appropriate use of these therapeutic modalities.

PMID- 11842842
TI  - A trigeminal neuralgia-like paroxysmal pain condition presumably due to buccal
      nerve compression in the temporalis muscle.
AB  - We encountered three patients with trigeminal neuralgia-like paroxysmal pain in
      the buccal nerve region. In all cases, paroxysmal pain was felt spreading to the
      receptive field of the ipsilateral buccal nerve, and clear tenderness was
      observed during intraoral palpation at the inner side of the mandibular ramus
      where the temporalis muscle runs and attaches. It was assumed that the paroxysmal
      pain might be caused by nerve compression related to temporalis muscle
      hyperactivity. To lend support to this hypothesis, we also studied the anatomical
      relationship between the buccal nerve and the masticatory muscles. In this
      autopsy study, the buccal nerve pierced the temporalis muscle in six (12%) of 52
      specimens from 26 cadavers. These findings support the hypothesis that peripheral
      buccal nerve compression could be an etiology of paroxysmal neuropathic pain in
      the unilateral orofacial region.

PMID- 11842843
TI  - Tooth wear: use of overlays with metallic structures.
AB  - This work is a clinical case report of a patient presenting with marked tooth
      wear in all teeth, a reduction in the vertical dimension of occlusion, and
      fatigue in the muscles of mastication. The treatment proposed and effected used a
      muscle-relaxing appliance and mandibular and maxillary overlay appliances which
      were adjusted according to the occlusal contacts, vertical dimension of
      occlusion, and the mandibular positioning. The results obtained were satisfactory
      in terms of relaxing the muscles involved, reestablishing the dimensions of the
      lower third of the face, and the functional activities of deglutition,
      mastication, and speech.

PMID- 11842844
TI  - The trigeminal nerve. Part II: the ophthalmic division.
AB  - The ophthalmic, or first division (V1) of the trigeminal nerve, is the smallest
      of the three divisions and is purely sensory or afferent in function. It supplies
      sensory branches to the ciliary body, the cornea, and the iris; to the lacrimal
      gland and conjunctiva; to portions of the mucous membrane of the nasal cavity,
      sphenoidal sinus, and frontal sinus; to the skin of the eyebrow, eyelids,
      forehead, and nose; and to the tentorium cerebelli, dura mater, and the posterior
      area of the falx cerebri. At first glance, one might not expect one interested in
      the diagnosis and treatment of orofacial pain and temporomandibular joint
      disorders to have a need to be concerned with the ophthalmic division. Although
      much of this division's influence is dedicated to structures within the orbit,
      nose, and cranium, still, the ophthalmic division may be afflicted with a lesion
      or structural disorder which can cause all sorts of orofacial pain. Ignorance of
      this or any portion of the trigeminal nerve will lead to diagnostic and
      therapeutic failures. In this, the second of four (4) articles concerning the
      trigeminal nerve, the first division of this vast cranial nerve will be described
      in detail.

PMID- 11842845
TI  - Human movement characteristics of target acquisition.
AB  - Objective. This paper deals with the problem of human movement characteristics of
      target acquisition. Method. A hypothetical model was posed by using experimental
      data. Result. The conception of final target size was put forward, an equation
      for calculating the movement time of target acquisition was obtained, and a new
      definition of index of difficulty was given. Conclusion. Analysis of experimental
      data showed that this equation could give a better description of target
      acquisition in a wide range.

PMID- 11842846
TI  - [The dynamic changes of NOSmRNA in endothelial cells of aortae and pulmonary
      arteries in rats under tail suspension].
AB  - Objective. Through the observations of dynamic changes of eNOSmRNA and iNOSmRNA
      in arterial endothelial cells of systematic circulation and pulmonary circulation
      under simulated weightlessness, to collect some data for studies of the adaptive
      mechanisms of local regulation in arterial systems. Method. Wistar rats were -30
      degrees tail suspended to simulate the effects of weightlessness. The rats were
      randomly divided into three groups: control group (CON), 7-day tail suspension
      group (TS7) and 14-day tail suspension group (TS14). Changes of NOSmRNA expresses
      in endothelial cells of the thoracic aortae and pulmonary arteries were observed
      with in situ hybridization technique. Result. The eNOSmRNA and iNOSmRNA of
      thoracic aortic and pulmonary arterial endothelial cells in TS7 rats increased
      very significantly. The eNOSmRNA of thoracic aortic endothelial cells from TS14
      rats returned to control level, but remained very significantly increased in
      pulmonary arteries. The iNOSmRNA in pulmonary arterial endothelial cells from
      TS14 rats decreased very significantly, but that in thoracic aortae returned to
      the control level. Conclusion. The responses of eNOSmRNA and iNOSmRNA in arterial
      endothelial cells of systematic circulation to tail suspension were similar, but
      they were different in pulmonary arterial endothelial cells, which might be due
      to the difference in the peak course of the shift of fluid from lower body
      entering the pulmonary or systematic circulation during initial period of
      simulated weightlessness. It could be a kind of important sign of depressed local
      regulative function under simulated weightlessness and might contribute to
      orthostatic intolerance after simulated weightlessness.

PMID- 11842848
TI  - [Analysis of heart rate variability during acute exposure to hypoxia].
AB  - Objective. To investigate the changes of autonomic nervous system during acute
      exposure to an altitude of 5000 m by analysing heart rate variability (HRV).
      Method. 11 healthy male volunteers aged 18-30 were observed during inhalation of
      low oxygen gas mixture to simulate acute exposure to hypoxia. HRV was analyzed
      with both time domain and frequency domain methods. The eleven subjects were
      divided into two groups--Group A with good tolerance and Group B with poor
      tolerance. Result. During hypoxia heart rate increased markedly and RMSSD (the
      square root of the mean squared differences of successive RR intervals) decreased
      markedly; normalized low-frequency (LFn. u.) and LF/HF ratio increased
      significantly, while HF and normalized high-frequency (HFn. u.) reduced
      significantly. LFn. u. and LF/HF increased more apparently in group B than in
      group A during hypoxia of 5-10 min and RMSSD decreased more in group B during 10
      15 min. Conclusion. The results suggested that cardiac sympathetic activity
      increased and cardiac vagal activity decreased during acute hypoxia. The analysis
      of HRV could predict the tolerance to hypoxia.

PMID- 11842849
TI  - [Effect of 7 d -6 degrees head-down tilt (HDT) on electromyogram of gastrocnemius
      and anterior tibialis muscles].
AB  - Objective. To assess the effect of 7 d -6 degrees HDT on electromyogram of the
      weightbearing muscles. Method. Eight healthy males, aged 33-42, were exposed to 
      6 degrees HDT bed-rest for 7 d, electromyogram from the gastrocnemius and
      anterior tibialis muscles were recorded before and after HDT, and day 4 of
      recovery. Result. The latency of SLR (short latency response) recorded from lower
      leg muscles after HDT was not different from that pre-HDT. But the latency of MLR
      (middle latency response) and LLR (long latency response) after HDT were
      significantly increased as compared with that pre-HDT, and recovered to pre-HDT
      level on day 4 of recovery. The durations of SLR recorded from right leg muscles
      after HDT were significantly longer as compared with that pre-HDT, and did not
      recover. The integrated amplitude of SLR and MLR after HDT were significantly
      increased as compared with that pre-HDT, and only the integrated amplitude of SLR
      recovered, but that of MLR did not. Conclusion. Seven day -6 degrees HDT bed-rest
      had significant effects on electromyogram of the weightbearing muscles.

PMID- 11842847
TI  - [Counter-effect of intermittent +Gz exposures on vasoreactivity in decline in
      hind body arteries of rats under simulated weightlessness].
AB  - Objective. To investigate the counter-effect of intermittent artificial gravity,
      the present study examined vasoreactivity changes of femoral and mesenteric
      arteries in rats subjected to simulated weightlessness plus standing or
      centrifugation. Method. Forty male Sprague-Dawley rats were divided into
      simultaneous control (CON), simulated weightlessness (SUS), simulated
      weightlessness plus 1 h standing (STD1), simulated weightlessness plus 1.5 G
      centrifugation (1.5 G), and simulated weightlessness plus 2.6 G centrifugation
      (2.6 G) groups. Responses of arteries to vasoconstrictor were examined in vitro
      using isolated femoral and mesenteric arterial rings. Result. The contractile
      responsiveness to KCl or PE of femoral and mesenteric arterial rings isolated
      from SUS significantly decreased as compared with CON. And those of STD1 and the
      two centrifuged groups significantly enhanced as compared with that of SUS.
      Whereas there was no difference among STD1, 1.5 G, 2.6 G and CON. Conclusion.
      Simulated weightlessness may result in decreased contractile responses to KCl and
      PE of rat femoral and mesenteric arteries. Both STD1, 1.5 G, and 2.6 G prevented
      the decrease of contractile response to KCl and PE of femoral arteries.

PMID- 11842850
TI  - [Effects of vitamin K on bone metabolism in tail-suspended rats].
AB  - Objective. To study the effects of vitamin K on bone metabolize in simulated
      weightlessness rats. Method. Male SD rats were divided into three groups (n = 9):
      the free active control (FAC), the tail-suspended control (SC), and the tail
      suspended group treated with vitamin K (SVK) (50 mg/kg weight/d). The experiment
      lasted for 3 weeks. Bone biomechanical properties, bone mineral contents (BMC)
      and bone biochemical markers of bone metabolism were determined. Result. Compared
      with SC, total and bound bone gla protein (BGP) of serum, BMC of the femur and
      tibia, femoral mechanical properties, ALP activity of tibia all increased
      significantly; while NO content of femoral trunk decreased significantly.
      Conclusion. Vitamin K improved the bone metabolism and bone structure, decreased
      bone loss, increased bone biomechanical properties, decreased catagmatic
      fatalness. It proved that vitamin K prevented bone loss of simulated
      weightlessness rats.

PMID- 11842851
TI  - [A biomechanical model of left ventricle regional ischemia: a computer
      simulation].
AB  - Objective. To analyze the biomechanical mechanism of left ventricular regional
      ischemia and to investigate the changes of myocardial contractilities in
      different ventricular regions during regional ischemia. Method. A time-dependent
      mathematical model for simulating left ventricle regional ischemia has been
      developed basing on geometry of left ventricle, spatial angle distribution,
      propagation of electrical activation signals and biomechanical properties of
      cardiac muscle fibers. Then the model was incorporated into a multi-element
      circulatory model established by us previously. By using this model, some
      simulation experiments relating myocardium contractility to regional ischemia in
      inner or outer layers of ventricular wall were performed. Result. Myocardial
      contractility of the ischemic layers decreased whereas that of normal layers
      increased significantly. Compared with ischemia in outer layers of ventricular
      wall, ischemia in inner layers of ventricular wall had more effects upon cardiac
      function. Conclusion. The myocardium of normal region had the ability to increase
      its contractility in order to maintain a normal cardiac function. A method to
      simulate the relationship between cardiovascular function and left ventricular
      regional ischemia was developed.

PMID- 11842852
TI  - [Feasibility of the use of degraded inedible biomass of plants as a nutrient
      liquid for hydroponic cultivation].
AB  - Objective. To demonstrate that the recycled liquid, which originated from lettuce
      inedible biomass degraded by fixed microorganism (correction of microorgannism)
      and enzyme, can be used as a nutrient solution for lettuce hydroponic
      cultivation. Method. After biologically degrading the weighted, oven-dried and
      milled leaves and roots of lettuce in a biological reactor under aerobic
      condition, the original effluent and its supplemented effluent were used as
      nutrients for lettuce hydroponic cultivation. Result. The average dried weight
      (ADW) of lettuce from the original effluent group was approximately half of that
      from the control group, and the ADW from supplemented effluent group was about
      equal to that from the control group; some qualities of the lettuce such as a
      relatively lower content of NO3- from both the original effluent group and the
      supplemented effluent one improved, and some of those such as a relatively higher
      content of NO2- dropped. Conclusion. The biologically-degraded effluent was able
      to be used as nutrient solution for lettuce hydroponic cultivation, although the
      effects of the inorganic ion-supplemented effluent were much better; the plants
      of lettuce from the biologically-degraded effluent were safely edible.

PMID- 11842853
TI  - Evidence to the independent inquiry into clinical trials in North Staffordshire.

PMID- 11842854
TI  - Report of the review into the research framework in North Staffordshire.
AB  - This review began because of complaints about the conduct of research studies in
      the paediatric department of the North Staffordshire Hospital in Stroke-on-Trent.
      As it progressed other issues were also examined such as diagnosing Munchausen's
      Syndrome by Proxy by the use of covert video surveillance. The following extracts
      concentrate on research issues, and include the whole of the framework for
      research governance outlined in the report.

PMID- 11842856
TI  - Preimplantation diagnosis--points to consider.

PMID- 11842855
TI  - Hospice in the nursing home--a valuable collaboration.
AB  - Long-term care facilities have one of the most difficult tasks in health care: to
      maximize the health of frail elderly people. However, our society's resistance to
      the natural process of dying commands the assistance of hospice services in
      helping patients and their families cope with illness and death. The presence of
      such hospice services in long-term facilities is relatively recent, and the two
      teams are still negotiating an optimal collaboration.

PMID- 11842857
TI  - Preimplantation genetic diagnosis (PGD) in a European context.
AB  - This paper reviews the main aspects of the ethical and legal stance on
      preimplantation genetic diagnosis taken in Germany, France, the United Kingdom
      and the Netherlands. Each of the four countries has taken a different line.
      Germany has taken a prohibitive approach, while France has a cautious regulatory
      system and the UK a liberal one. The Netherlands does not yet have legislation
      which applies directory to PGD.

PMID- 11842858
TI  - How to become an ethicist? A narrative reflection.

PMID- 11842859
TI  - Adults with Incapacity (Scotland) Act 2000--excerpt.

PMID- 11842860
TI  - Embryonic stem cells and totipotency.

PMID- 11842861
TI  - Sleep disturbance in orofacial pain patients: pain-related or emotional distress?
AB  - Associations between pain, depression, and sleep disturbance have been documented
      in several chronic pain patient samples. The current study assessed the
      prevalence and magnitude of sleep disturbance in a sample of 128 orofacial pain
      patients referred for clinical evaluation and tested linkages between sleep,
      depression, anxiety, and pain using cross-sectional and longitudinal data.
      Seventy-seven percent of the patients reported reduced sleep quantity since pain
      onset. In cross-sectional analyses, reduced sleep quantity was associated with
      depression and pain. Reduced sleep quality was associated with negative affect.
      Longitudinally, initial depression and pain predicted sleep at time two and
      initial pain predicted negative affect. Sleep did not predict pain. Results
      support the hypothesis that pain, rather than sleep disturbance, increases
      negative affect across time, whereas negative affect is more a cause of
      concurrent reduced sleep quality than is pain. The results highlight the
      importance of assessing for sleep disturbance in orofacial pain patients.

PMID- 11842862
TI  - Oral jaw behaviors in TMD and bruxism: a comparison study by severity of bruxism.
AB  - The purpose of this study was to document the prevalence of oral jaw behaviors
      concomitant to bruxism in TMD+bruxing behavior patients and in nonbruxer
      controls. Clinical examination, questionnaires, and specific criteria to allocate
      patients to mild, moderate, and severe groups of TMD and bruxers were used. The
      sample consisted of 274 TMD+bruxing behavior patients and 52 control non-bruxing
      behavior groups evaluated at the Center for the Study of TMD. The mean age of the
      TMD+bruxing behavior group was about 33.11 years old (range 16.66, SD = 11.52) as
      compared to 34.90 years old (range 17-67, SD = 14.26) in the control group. Oral
      jaw behaviors were assessed in the mild, moderate, and severe TMD+bruxing groups,
      and in the corresponding control group. It was found that the prevalence of oral
      jaw behaviors was higher in the TMD+bruxing behavior group as compared to the
      control. Hence, concomitant oral jaw behaviors predominated in bruxers and
      increased with its severity. The data reinforce the need to assess TMD patients
      in terms of the presence of bruxism, its severity, and concomitant oral jaw
      habits. Such approach will enable the clinician to have better understanding
      about the role of these behaviors in TMD. Epidemiological data was also provided
      regarding jutting the jaw forward (a rarely-described oral jaw habit) in a
      relatively large sample of TMD+bruxing patients, suggesting a more clinical
      intervention in children and adolescents. This study is the first to document the
      prevalence of specific oral jaw habits in a relatively large sample of
      TMD+bruxing behavior classified by degree of severity. Results suggest that
      TMD+bruxing patients may present many other additional oral jaw habits which may
      concur to increase masticatory muscle activity thus leading to TMD signs and
      symptoms. Factors responsible for the increased frequency of oral jaw habits with
      the severity of bruxism behavior remain unknown and therefore further studies are
      needed.

PMID- 11842863
TI  - Emotional stress and craniomandibular dysfunction in children.
AB  - This study investigated the relationship between craniomandibular dysfunction
      (CMD) and emotionally stressful states measured by the urinary catecholamines in
      314 children aged six to eight years. The children were examined clinically and
      interviewed by the same investigator. During the clinical examination the
      following variables were recorded: maximal mouth opening with and without pain,
      deviation of the mandible in opening wide, muscle and temporomandibular joint
      (TMJ) tenderness or pain and sounds from the TMJ. The variables recorded during
      the interview were headaches, difficulties in opening wide, pain upon opening
      wide, and clicking. A questionnaire was distributed to the parents to collect
      information regarding socioeconomic factors. A 24-hour urine sample was collected
      for each subject and analyzed by the high performance liquid chromatography
      (HPLC) technique to assay the catecholamine content. The logistic multiple
      regression analysis was carried out to test whether craniomandibular dysfunction
      was affected by the studied variables. A 95% probability level was used. The
      results showed that epinephrine had a significant effect on TMJ tenderness, while
      norepinephrine and dopamine did not have a significant association with any of
      the signs and symptoms of CMD. The data suggest that emotionally stressful states
      increase the probability of developing TMJ tenderness in children of this age.

PMID- 11842865
TI  - The clinical evaluation of posture: relationship of the jaw and posture.

PMID- 11842864
TI  - A randomized double-blind clinical trial of the effect of chondroitin sulfate and
      glucosamine hydrochloride on temporomandibular joint disorders: a pilot study.
AB  - Previous studies have shown chondroitin sulfate and glucosamine hydrochloride
      have beneficial effects on symptoms of osteoarthritis of the knee. Our aim was to
      study the effect of a daily dose of 1500 mg of glucosamine hydrochloride (GH) and
      1200 mg of chondroitin sulfate (CS) taken for twelve weeks on subjects diagnosed
      with capsulitis, disk displacement, disk dislocation, or painful osteoarthritis
      of the temporomandibular joint (TMJ). Forty-five subjects were enrolled in the
      study and were randomly assigned to either an active medication group or a
      placebo group. Eleven subjects were lost from the study for various reasons,
      resulting in fourteen subjects remaining in the active medication group and
      twenty subjects remaining in the placebo group. Subjects taking CS-GH had
      improvements in their pain as measured by one index of the McGill Pain
      Questionnaire, in TMJ tenderness, in TMJ sounds, and in the number of daily over
      the-counter medications needed. Subjects taking the placebo medication had
      improvements in their pains as measured by the visual analog scale and by four
      indices of the McGill Pain Questionnaire. Additional studies are required to
      evaluate the clinical effectiveness of CS-GH and to determine the exact mechanism
      by which CS-GH affects the articular cartilage of synovial joints.

PMID- 11842866
TI  - Electronic diagnostic aids: A role in dental education?

PMID- 11842867
TI  - Controlling knowledge.

PMID- 11842868
TI  - The trigeminal nerve. Part III: The maxillary division.
AB  - The maxillary nerve gives sensory innervation to all structures in and around the
      maxillary bone and the midfacial region including the skin of the midfacial
      regions, the lower eyelid, side of nose, and upper lip; the mucous membrane of
      the nasopharynx, maxillary sinus, soft palate, palatine tonsil, roof of the
      mouth, the maxillary gingivae, and maxillary teeth. This vast and complex
      division of the trigeminal nerve is intimately associated with many sources of
      orofacial pain, often mimicking maxillary sinus and/or temporomandibular joint
      involvement. For those who choose to treat patients suffering with orofacial pain
      and temporomandibular disorders, knowledge of this nerve must be second nature.
      Just providing the difficult services of a general dental practice should be
      stimulus enough to understand this trigeminal division, but if one hopes to
      correctly diagnose and treat orofacial pain disorders, dedication to
      understanding this nerve cannot be overstated. In this, the third of a four part
      series of articles concerning the trigeminal nerve, the second or maxillary
      division will be described and discussed in detail.

PMID- 11842869
TI  - Wavelet transforms of TM joint vibrations: a feature extraction tool for
      detecting reducing displaced disks.
AB  - The objective of this study was to determine if wavelet transforms (WTs) of
      vibrations recorded from temporomandibular joints (TMJs) with reducing displaced
      disks could be visually separated from WTs of vibrations recorded from normal TM
      joints by blinded observers. From a continuous series of 124 diagnosed TMD
      patients, 28 were confirmed with at least one reducing displaced disk. Vibrations
      were recorded from each affected joint, together with incisal point movements,
      using BioPAK (BioResearch, Inc., Milwaukee, WI) during opening, closing, and
      lateral excursions. Identical recordings were taken from 28 patients who were
      determined to have normal "nondisplacing, nondisplaced" joints. A 3x7
      Biorthogonal Spline Wavelet Transform was used to create three-dimensional time
      frequency graphs of the vibration events for each subject. Printed copies of the
      graphs were then shown sequentially to seven blinded observers who were asked to
      separate them into two groups without any knowledge of their significance. Each
      observer was independently able to separate the two groups without committing
      more than one error. We conclude that the vibrations generated by reducing
      displaced disks are sufficiently different from the vibrations of normal joints
      to be separable by visual inspection of their respective wavelet transforms.

PMID- 11842870
TI  - Condylar hyperplasia associated to synovial chondromatosis of the
      temporomandibular joint: a case report.
AB  - Condylar hyperplasia is a slowly developing malformation of the mandible, with
      elongation of the mandibular neck, that generally results in facial asymmetry.
      Synovial chondromatosis is a benign chronic disorder characterized by the
      formation of multiple small nodules of hyaline cartilage as a result of
      metaplasia of the synovial connective tissue. It affects mostly the large joints,
      particularly the knee, hip, elbow and ankle. The temporomandibular joint (TMJ) is
      rarely affected. The case of a 42-year-old male with a history of left
      preauricular pain and swelling and deviation of the mandible to the left upon
      opening the mouth is presented. Computed tomography disclosed hyperplasia of the
      left condyle with loose radiopaque bodies within the joint cavity. The left TMJ
      was subject to open surgery, which included resection of four loose bodies and a
      remodeling condylectomy. The histopathological study confirmed the diagnosis of
      condylar hyperplasia and chondromatosis of the left TMJ.

PMID- 11842871
TI  - Translation and rotation of the mandible during habitual mouth opening movement
      in children with anterior reverse bite in the primary dentition.
AB  - Translation and rotation of the mandible during habitual mouth opening movements
      were studied in 13 children with skeletal-based anterior reverse bite (reverse
      bite group) and in 13 children with normal occlusion (normal occlusion group)
      whose dental stage was the primary dentition. Movements were recorded by an opto
      electronic movement-analyzing system that could measure mandibular movements with
      six degrees of freedom. Inferior translation of the mandible was analyzed at the
      left primary central incisor, both of the primary canines, and both of the
      primary second molars. Anterior translation of the mandible was analyzed at both
      of the condyles. Rotation of the mandible was measured in the sagittal plane. The
      results showed that the associations between the translation and rotation of the
      mandible during habitual mouth opening in the reverse bite group differed from
      those in the normal occlusion group. The reverse bite group had greater anterior
      translation of both of the condylar points than did the normal occlusion group.
      No significant differences were found in the inferior translation or rotation of
      the mandible between the two groups.

PMID- 11842872
TI  - The role of taste in the recovery from specific nutrient deficiencies in rats.
AB  - Humans and animals have an impressive ability to use behavioral means to recover
      from nutritional deficits. Under some conditions, recovery ray be manifest in the
      form of a specific appetite for the missing nutrient. This review will discuss
      how the gustatory system is used by the rat to aid in the recovery from
      deficiencies of sodium, vitamin B, and individual essential amino acids. While it
      is likely that a deficient rat will use all available cues to guide intake of a
      limited nutrient, the role of taste can be partitioned out using techniques that
      measure immediate behavioral responses to brief exposures of taste stimuli and/or
      by measuring responsiveness before and after nerve transection. Taste can be used
      to identify stimuli in the environment as well as serve to motivate intake in
      terms of producing a particular affective reaction. Compensatory alterations in
      these aspects of the gustatory system are considered for three types of
      deficiencies. For learned appetites the utility of conditioning paradigms is
      presented as a potential means to gain a further understanding of behavioral
      recovery from specific micronutrient deficiencies.

PMID- 11842873
TI  - Expression of transferrin mRNA in rat oligodendrocytes is iron-independent and
      changes with increasing age.
AB  - As transferrin in the brain may originate principally from synthesis by three
      different cell types, i.e. hepatocytes, oligodendrocytes and choroid plexus, this
      study employed a morphological analysis to specifically address oligodendrocytic
      expression of transferrin mRNA in young (P17) and adult (P50) rats. In spite of a
      lowering of the concentration of brain iron by approximately 22% in the young
      iron deficient rats transferrin mRNA expression in oligodendrocytes was not
      affected when measured by quantitative densitometry. In adult rats, the baseline
      transferrin mRNA expression in oligodendrocytes was higher than in the young
      animals, but did not change in spite of a reduction in brain iron by
      approximately 19%. Brain iron and transferrin mRNA expression in oligodendrocytes
      were unaltered in iron overloaded rats when compared to age-matched controls. As
      transferrin expression was lower in the young rat, when constituents from the
      blood have a relatively higher concentration in the brain than during adulthood,
      it seems unlikely that blood-borne factors such as transition metals act as
      inducers of transferrin gene expression in oligodendrocytes. Instead, the higher
      but constitutive expression of transferrin mRNA at later ages, when the blood
      brain barrier segregates the brain from other body parts, may indicate that
      molecules released from the brain interior are responsible for regulating
      transcription of the transferrin gene.

PMID- 11842874
TI  - Reports on dietary intervention in autistic disorders.
AB  - Autism is a developmental disorder for which no cure currently exists. Gluten
      and/or casein free diet has been implemented to reduce autistic behaviour, in
      addition to special education, since early in the eighties. Over the last twelve
      years various studies on this dietary intervention have been published in
      addition to anecdotal, parental reports. The scientific studies include both
      groups of participants as well as single cases, and beneficial results are
      reported in all, but one study. While some studies are based on urinary peptide
      abnormalities, others are not. The reported results are, however, more or less
      identical; reduction of autistic behaviour, increased social and communicative
      skills, and reappearance of autistic traits after the diet has been broken.

PMID- 11842875
TI  - Plasma leptin and hypothalamic neuropeptide Y and galanin levels in Long-Evans
      rats with marked dietary preferences.
AB  - Neuropeptides present in the hypothalamus and new messengers in the periphery
      such as leptin modulate food intake in mammals. Neuropeptide Y (NPY) and galanin
      in microdissected brain areas and plasma leptin levels were measured by specific
      radioimmunoassays during the resting period in rats selected for their strong
      preference either for carbohydrate or fat, but with identical energy intake. NPY
      concentrations were 23% lower (p <.02) in carbohydrate-preferring (CP) than in
      fat-preferring (FP) rats in the parvocellular part of the paraventricular nucleus
      (PVN), which is one of the main areas involved in the regulation of feeding
      behavior. On the other hand, galanin was significantly (+25%, p = .03) higher in
      CP rats than in FP rats in the magnocellular part of the PVN. Plasma leptin was
      more than 50% higher in FP rats than in CP rats (p < .01) and highly correlated
      with the fat preference (r = 0.57; p = .003) and body weight gain. We conclude
      that the rats with a spontaneous and marked dietary preference have a
      characteristic peptidergic profile. Due to their anatomical relationships,
      neuropeptide Y could act in conjunction with galanin in a peptidergic balance
      located in the paraventricular nucleus. This model integrates information
      provided by the energy stores and translated by peripheral messengers such as
      leptin which could act in a counterregulatory manner in order to limit the
      overweight induced by the ingestion of unbalanced diets.

PMID- 11842876
TI  - Amino acid levels and ratios in serum and cerebrospinal fluid of patients with
      optic neuropathy in Cuba.
AB  - Twenty-one amino acids were determined in serum and cerebrospinal fluid of 12
      patients with endemic, and in the cerebrospinal fluid of 22 patients with
      epidemic optic neuropathy. For the endemic patients, there was a decrease in
      aspartate and taurine in the serum with respect to controls. The ratios
      aspartate/taurine and taurine/valine were decreased, and glutamate/taurine was
      increased in the serum. Some of the altered amino acid ratios indicate
      preponderance of excitatory to inhibitory molecules. The ratio with valine
      corresponded to the decrease in taurine and the maintenance of valine
      concentration, an amino acid related to anthropometric parameters. A typical
      malnutrition pattern was not observed, as the levels of essential amino acids
      were not significantly modified. In the cerebrospinal fluid there were increases
      in aspartate, glutamate and threonine, the first two probably indicating a
      neurodegenerative disorder or some type of metabolic alteration, primary or
      secondary to the disease. The increase in threonine could be related to lipid
      metabolism, but it is not clear at present. A wide variety of amino acid ratios
      were increased in the cerebrospinal fluid of patients with endemic optic
      neuropathy, mainly pointing to an excitatory condition and some metabolic
      alterations. In the cerebrospinal fluid of patients with epidemic optic
      neuropathy there was an increase in aspartate and glutamate, and increase in
      glutamate/taurine, glutamate/glycine, and gamma-aminobutyric acid/glycine ratios.
      Interesting differences were also observed between patients from different
      periods of time, but with the same clinical features, and the modifications of
      amino acid concentrations in the cerebrospinal fluid, such as glutamine,
      threonine and tryptophan. The present results indicate a disorder in the
      metabolism of amino acids, support a specific deficit, especially for taurine, an
      imbalance between excitatory and inhibitory amino acids, and a possible relation
      to viral infections.

PMID- 11842877
TI  - Effects of pure macronutrient ingestion on plasma tryptophan and large neutral
      amino acids.
AB  - The role of tryptophan and its competitor large neutral amino acids, proposed
      earlier for serotonin synthesis following carbohydrate or protein ingestion, was
      reassessed in relation to a recent study investigating serotonin release,
      including the so far unknown effects of fats. In the present study, meals of
      either carbohydrates, casein, or lard, were supplied to rats for 30 min and blood
      samples collected every 15 min to follow the changes in plasma large neutral
      amino acids. In response to carbohydrates, amino acid levels fell and the ratio
      tryptophan over sum of other amino acids increased. Following casein ingestion,
      all amino acids were enhanced, tryptophan somewhat less, leading to a decreased
      ratio. The lard meal induced a slight decrease in some amino acids while the
      ratio remained constant. Only in response to casein, and partly to carbohydrates,
      did a consistent relation appear between the previously observed serotonin
      changes and the ratio. These data suggest that a relationship between the ratio
      and the previously observed serotonin changes is not always encountered because
      the release is not obligatorily coupled to synthesis and is subject to behavioral
      influences. It remains that serotonin release is affected by the composition of
      the meal through peripheral metabolic mechanisms.

PMID- 11842878
TI  - Treatment of hemorrhagic stroke with arachidonic acid.
AB  - Eighty-seven year old man, previously healthy, active and independent, was
      admitted to a hospital unconscious with hemorrhagic stroke. Treatment with
      arachidonic acid was initiated two weeks after his admission. After one year,
      despite his age, large hemorrhagic area and a history of ischemic heart disease,
      he had no physical disability or mental impairment and scored 95 points on the
      Barthel Scale.

PMID- 11842879
TI  - Development and modulation of GABA(A) receptor-mediated neurotransmission in the
      CA1 region of prenatally protein malnourished rats.
AB  - Prenatal protein malnutrition has been demonstrated to result in alterations in
      the serotonergic and GABAergic neurotransmitter systems in the rat hippocampus.
      In the present study, whole-cell patch clamp recordings of CA1 pyramidal cells
      were employed in an effort to gain insight into the specific cellular locus and
      functional consequences of the previously reported changes. Hippocampal slices
      were prepared from Sprague-Dawley rats whose dams were fed either a normal (25%
      casein) or low (6% casein) protein diet during pregnancy. The development of
      GABA(A) receptor-mediated miniature inhibitory postsynaptic currents (mIPSCs) and
      their modulation by the benzodiazipine agonist zolpidem were compared in cells
      from the two nutritional groups at postnatal days 7, 14, 21 and >90. The
      modulation of mIPSCs by serotonin was also examined in cells from 21 day old
      rats. No significant differences were observed in the characteristics of mIPSCs
      in cells from control vs. prenatally protein malnourished rats at any of the ages
      studied, although there was a trend for a higher frequency of mIPSCs in adult
      (>p90) prenatally protein malnourished rats. At all ages, zolpidem produced a
      significant increase in the mean decay time of mIPSCs that was not significantly
      different in cells from the two nutritional groups. Serotonin application
      resulted in a significant increase in the frequency of mIPSCs in CA1 pyramidal
      cells but there was no significant difference between cells from the two
      nutritional groups in the characteristics of this effect. These data demonstrate
      that the previously observed alterations in the serotonergic and GABAergic
      systems that result from prenatal protein malnutrition do not have significant
      functional consequences at a single cell level in the CA1 region of the rat
      hippocampus as measured in vitro.

PMID- 11842880
TI  - The influence of soy-derived phosphatidylserine on cognition in age-associated
      memory impairment.
AB  - Phosphatidylserine (PS) is a phospholipid widely sold as a nutritional
      supplement. PS has been claimed to enhance neuronal membrane function and hence
      cognitive function, especially in the elderly. We report the results of a
      clinical trial of soybean-derived PS (S-PS) in aging subjects with memory
      complaints. Subjects were 120 elderly (> 57 years) of both sexes who fulfilled
      the more stringent criteria for age-associated memory impairment (AAMI); some
      also fulfilled the criteria for age-associated cognitive decline. Subjects were
      allocated at random to one of the three treatment groups: placebo, 300mg S-PS
      daily, or 600mg S-PS daily. Assessments were carried out at baseline, after 6 and
      12 weeks of treatment, and after a wash-out period of 3 weeks. Tests of learning
      and memory, choice reaction time, planning and attentional functions were
      administered at each assessment. Delayed recall and recognition of a previously
      learned word list comprised the primary outcome measures. No significant
      differences were found in any of the outcome variables between the treatment
      groups. There were also no significant interactions between treatment and
      'severity of memory complaints'. In conclusion, a daily supplement of S-PS does
      not affect memory or other cognitive functions in older individuals with memory
      complaints.

PMID- 11842882
TI  - Action of CCK and 5-HT on lateral hypothalamic neurons depends on early postnatal
      nutrition.
AB  - Wistar rats grown up during the early postnatal life (3-21 days after birth) in
      artificially built normal, small or large lifters developed a significantly
      different body weight. This difference persisted also during adulthood when they
      had free access to food and water. The influence of iontophoretically
      administered cholecystokinin (CCK8S), serotonin (5-HT) or co-ejection of both on
      firing of lateral hypothalamic neurons was investigated in adult, urethane
      anesthetized rats of the three groups. The responsiveness to CCK8S was
      significantly higher in large- and small-litter rats than in the normal control
      group. The differences were greater in males than in females. They resulted in
      the male large-litter group from an increase of excitatory responses, whereas in
      the male small-litter group the proportion of inhibitory responses was augmented.
      Co-administration of 5-HT generally reduced the neuronal responsiveness.
      Especially in the large-litter group excitatory responses were significantly
      reduced. It may be speculated that the availability of food in the early
      postnatal life influences the development of the hypothalamic regulatory network
      in such a way that it stabilizes the high or low food ingestion all the life. At
      least in males, a changed responsiveness and type of response to cholecystokinin
      of lateral hypothalamic neurons might be involved in this altered regulation.

PMID- 11842881
TI  - Minimal effects from developmental exposure to St. John's wort (Hypericum
      perforatum) in Sprague-Dawley rats.
AB  - Increasing widespread use of St. John's Wort (SJW, Hypericum perforatum) has led
      to concerns about its use in pregnant women. Behavioral and physiological
      alterations resulting from developmental treatment were investigated in Sprague
      Dawley rats exposed to diets containing 0, 180, 900, 1800 or 4500ppm SJW
      beginning on gestational day 3 and ending at offspring weaning on postnatal day
      (PND) 21. These dietary doses span 1-25 times the recommended human dose. Post
      weaning behavioral assessments of male and female offspring included: open field
      activity, acoustic startle, performance of complex and Morris water mazes, and
      activity in an elevated plus-maze. There were no SJW effects on maternal weight
      gain or duration of gestation; offspring body weights were similar to controls
      from PND 2 through PND 56 after which, some treated groups weighed significantly
      less than the controls. There were no SJW-related behavioral alterations on any
      measure. Whole and regional brain weights of offspring at adulthood indicated no
      significant effects of SJW. These results indicate that there are few
      neurobehavioral alterations resulting from developmental SJW treatment in rats.

PMID- 11842883
TI  - Diet restriction in mice causes a decrease in hippocampal choline uptake and
      muscarinic receptors that is restored by administration of tyrosine: interaction
      between cholinergic and adrenergic receptors influencing cognitive function.
AB  - We have studied the effects of diet restriction (DR) to 60% and 40% of daily
      requirements, and tyrosine administration on cognitive function in mice, to
      define the nutritional-neurochemical interactions on autonomic tone involved in
      behavior and energy regulation. Cognitive function in the Morris Water maze was
      significantly impaired after 40% DR compared to both control and 60% DR. It was
      restored after tyrosine in association with increased M1 cholinergic and beta
      adrenergic receptor function, and decreased alpha-adrenergic function. DR to 40%
      significantly decreased choline uptake (p <.05) and M1 receptor number (Bmax) (p
      <.05), without changes in affinity (Kd), choline acetyl transferase (ChAT) or
      acetyl cholinesterase (AChE) activity. Tyrosine administration significantly
      increased choline uptake (Bmax) (p <.05) and M1 density in the 40% DR (p <.01)
      without changes in affinity. ChAT activity was decreased after tyrosine-
      significantly after 40% DR (p <.05) while AChE was not affected. Both M1 mRNA and
      protein were not influenced by DR or tyrosine administration. Tyrosine
      hydroxylase mRNA was decreased significantly by 40% DR (p <.01). The effect of DR
      and tyrosine appeared to be both pre- and post-synaptic, indicating modulation of
      cholinergic activity by adrenergic tone. Nutritional effect on behavior and
      autonomic tone may have implications for the treatment of mood changes associated
      with weight loss and semi-starvation.

PMID- 11842884
TI  - Selenium and the brain: a review.
AB  - Similar to other tissues selenium from selenomethionine is deposited in the brain
      at higher concentrations than selenium in other forms. Vitamin E has a greater
      effect than selenium in reducing lipid peroxidation in various brain regions.
      Selenium does not have as great effect on glutathione peroxidase (GPX) activity
      in the brain as in most other organs. Prolonged selenium and iodine deficiencies
      will compromise thyroid hormone homeostatus in the brain and this is due to
      changes in deiodinases activities and lipid peroxidation. Even though selenium
      deficiency results in reduced GPX activity and selenium content in the brain,
      there is no reduction in thioredoxin reductase activity or selenoprotein W
      levels. Selenoprotein P is taken up in greater amounts by the brain but not by
      other organs in selenium deficient animals, suggesting a critical function of
      this selenoprotein in this organ. Selenium will influence compounds with hormonal
      activity (and neurotransmitters) in the brain, and this is postulated to be the
      reason selenium affects moods in humans and behavior in animals. Even though
      selenium counteracts the neurotoxicity of mercury, cadmium, lead and vanadium, it
      causes them to accumulate in the brain, presumably in a nontoxic complex.

PMID- 11842886
TI  - The influence of phosphatidylserine supplementation on mood and heart rate when
      faced with an acute stressor.
AB  - There have been previous reports that supplements of phosphatidylserine (PS)
      blunted the release of cortisol in response to exercise stress and that it
      improved mood. The present study extended these observations by considering
      whether PS supplementation influenced subjective feelings of stress and the
      change in heart rate when a stressful mental arithmetic task was performed. In
      young adults, with neuroticism scores above rather than below the median, the
      taking of 300mg PS each day for a month was associated with feeling less stressed
      and having a better mood. The study for the first time reports an improvement in
      mood following PS supplementation in a sub-group of young healthy adults.

PMID- 11842885
TI  - Effects of low-protein diet on the baroreflex and Bezold-Jarisch reflex in
      conscious rats.
AB  - The present study evaluated the effects of a low-protein diet (LP, 6% protein) on
      cardiovascular reflexes of Male Fisher rats. Three experimental groups, and their
      respective controls (15% protein), were used: (1) Baroreceptor reflex (BAR); (2)
      Bezold-Jarisch reflex (BJR); and (3) Prazosin treated. Dietary restriction began
      after weaning (three weeks) and lasted for a period of five weeks, after which
      animals were subjected to the experimental protocols. The BAR group was evaluated
      through injections of phenylephrine (0.5-5.0 microgram/Kg, i.v.) and sodium
      nitroprusside (0.7-7.0 microgram/Kg, i.v.) while the BJR was evaluated through
      injections of serotonin (2.5-10 microgram/Kg, i.v.). Our results showed an
      increased baroreflex gain bradycardia for the LP group (-0.96+/-0.34 vs. -2.12+/
      1.06 bpm/mmHg) and a larger bradycardia for the BJR the LP group (160+/-18%
      greater than controls). Basal cardiovascular parameters were not different
      between LP and control rats, however LP animals treated with prazosin resulted in
      a larger fall of blood pressure (-19+/-3 vs. -28+/-5 mmHg). In conclusion, LP
      rats present an increased responsiveness of BAR and BJR, which could contribute
      to their normal levels of cardiovascular parameters, in spite of the possible
      increase in the sympathetic vasomotor tonus observed with the prazosin protocol.

PMID- 11842887
TI  - Delta9-tetrahydrocannabinol stimulates palatable food intake in Lewis rats:
      effects of peripheral and central administration.
AB  - To further study effects of delta9-tetrahydrocannabinol (THC) on food intake,
      male Lewis rats were maintained on rat chow and, on testing days, presented with
      chocolate cake batter (CCB) for 4h in addition to chow. Chow intake was not
      affected by THC administration in either experiment. In experiment 1 (n = 13) THC
      was administered intraperitoneally, and low doses produced increases in CCB
      intake for up to 1 h while the highest dose significantly decreased CCB intake
      over this same time period. In experiment 2 (n = 10) THC was injected
      intracerebroventricularly. Doses of 2.5, 10 and 25 microg significantly increased
      CCB intake for up to 1 h while stimulatory effects following 5 microg lasted up
      to 2h. Overall THC produced short-term increases in palatable food intake
      following both peripheral and central administration. Intraperitoneal
      administration resulted in an "inverted U" dose-response curve at all time
      points, while all central doses resulted in increased intake early in the time
      course and the hyperphagic effects were of greater duration than those following
      peripheral administration.

PMID- 11842888
TI  - Malnutrition and environmental stimulation in rats: interpeak intervals of the
      brainstem auditory evoked potentials.
AB  - The aim of this study was to investigate the effects of malnutrition, nutritional
      recovery, environmental stimulation and click intensity on the interpeak
      intervals of the waves of the Brainstem Auditory Evoked Potentials (BAEPs). The
      animals were divided into Well-nourished (W) and Malnourished (M) groups. At
      weaning, half of the M rats were submitted to nutritional recovery (R) until the
      test day. These groups were further subdivided into Stimulated (S) and Non
      stimulated (N) rats. The BAEPs interpeak intervals I-III, I-IV and III-IV were
      analysed in independent groups of rats on the 18th, 22nd, 32nd and 42nd days of
      age. During the lactation period, stimulated rats presented shorter I-III, I-IV
      and III-IV interpeak intervals than Non-stimulated animals. This analysis also
      indicated a diet x stimulation x age interaction during the lactation period. The
      WN and MN groups showed a longer I-IV interval than the WS and MS groups,
      respectively, on the 18th and 22nd day of age, and the MN group also presented a
      longer I-IV interpeak interval than the WN group on the 22nd day of age. During
      the post-lactation period, stimulated animals showed shorter I-III and I-IV
      intervals than non-stimulated rats. Post hoc analysis indicated longer I-III and
      I-IV interpeak intervals in the MN than in the WN, RN and MS groups.
      Additionally, malnourished animals showed longer I-III and I-IV intervals than
      well-nourished and recovered rats when exposed to clicks of 90, 80 or 70 dB
      intensity. Malnutrition resulted in a delay of normal development of the
      brainstem auditory pathway indicated by the increases in the interpeak intervals
      of BAEPs waves, and environmental stimulation reduced these intervals, promoting
      faster nervous impulse transmission.

PMID- 11842889
TI  - Malnutrition and environmental stimulation in rats: wave latencies of the
      brainstem auditory evoked potentials.
AB  - It has been shown that environmental stimulation may reduce the damage caused by
      malnutrition to morphological and behavioural parameters; however, there are no
      data on the effects of stimulation on the Brainstem Auditory Evoked Potentials
      (BAEPs). The aim of this study was to evaluate the effects of protein
      malnutrition, nutritional recovery and environmental stimulation on the BAEPs of
      the rat. On the first day of life, the animals were divided into Well-nourished
      (W) and Malnourished (M) groups. At weaning, half the M rats were submitted to
      nutritional recovery (R) until the test day. All groups were subdivided into
      Stimulated (S) and Non-Stimulated (N) rats. BAEPs was tested in animals exposed
      to clicks of 90, 80 and 70 dB of intensity. The BAEPs latencies of waves I, II,
      III and IV in the left ear were analysed in independent groups of rats on the
      14th, 18th, 22nd, 32nd, and 42nd days of age. Statistical analysis showed diet
      and environmental stimulation interaction on the latencies of waves I, II, III
      and IV at all tested ages. WN rats showed longer latencies of waves I, II, III
      and IV than WS rats, and MN rats also showed longer latencies of these waves
      compared to WN, MS and RN at all tested ages. The results showed that
      malnutrition caused a delay in the latency of all BAEPs waves in rats of all
      ages. However, environmental stimulation reduced these latencies, reversing some
      damage caused by malnutrition. These data suggest that the auditory brainstem
      pathway is vulnerable to nutritional insults, and its structures show plasticity
      with environmental stimulation.

PMID- 11842890
TI  - Sulfur amino acid deficiency depresses brain glutathione concentration.
AB  - Dietary sulfur amino acid content is a major determinant of glutathione
      concentration in some tissues. We examined whether brain glutathione (GSH), a key
      component of antioxidant defense important for minimizing ischemic injury, was
      also responsive to short-term sulfur amino acid deficiency. Female Long-Evans
      adult rats were fed a sulfur-deficient L-amino acid defined diet for five days;
      the control diet was supplemented with L-cystine and L-methionine (n = 6). Sulfur
      amino acid deficiency was confirmed by a reduction in liver cysteine and GSH
      concentrations, marked decreases in food intake, and weight loss. GSH
      concentration analyzed by reverse-phase high performance liquid chromatography
      was significantly depressed in the neocortex and thalamus of deficient rats.
      Brain cysteine was not decreased in a parallel manner. Classical glutathione
      peroxidase activity was increased in the liver and brain of sulfur amino acid
      deficient rats. This suggests an upregulation of antioxidant defense but these
      findings may be complicated by alterations in tissue composition. The depletion
      of brain GSH by a reduced supply of dietary precursors may be important during
      brain ischemia when the rate of GSH utilization and the need for synthesis are
      increased.

PMID- 11842891
TI  - The GAbAergic and cholinergic systems in the retina are differentially affected
      by postnatal malnutrition during the suckling period.
AB  - Malnutrition by severe protein deprivation induces deleterious consequences in
      the nervous system particularly in the initial period of development. These
      deficits can alter several important events during development, such as the
      expression of neurotransmitters. The induction of nutritional deficiency by using
      low protein diet, similar to that consumed by low income populations in Brazil,
      was applied in rats to investigate the effect of malnutrition on cells containing
      gamma-aminobutyric acid (GABA) and acetylcholine in the retina. GABA
      immunoreactivity was present in cells in the inner nuclear and ganglion cell
      layers and in processes in the inner and outer plexiform layers in retinas of
      control and malnourished animals. At postnatal day 8, there is a decrease (ca.
      40%) of the GABAergic neurons in malnourished animals. At P13 and P21 the
      percentage of these neurons increased and was equivalent to control animals in
      the adult. Glutamic acid decarboxylase activity did not show significant changes
      between the two groups along development. Choline acetyltransferase
      immunoreactivity was localized in amacrine cells in the inner nuclear and
      ganglion cell layers and their processes in the inner plexiform layer. The
      percentage of cholinergic cells was always higher in malnourished animals than
      that observed in the control until postnatal day 30, when the same proportion of
      cholinergic neurons was found in the retinas of both groups. Choline
      acetyltransferase activity did not show significant changes between the two
      groups along development. In conclusion, our results show that despite the
      extreme somatic and behavioral changes observed the neurotransmitter systems
      studied were at a certain extent shielded from the insult.

PMID- 11842892
TI  - Effects of mercaptoacetate on feeding, circulating glucose and lipids, and
      gastric emptying in rats fed a carbohydrate-free high-fat diet.
AB  - In the present study we investigated whether glucose deprivation contributes to
      feeding induced by mercaptoacetate (MA), an inhibitor of fatty acid oxidation, in
      Sprague-Dawley rats fed a carbohydrate-free, high-fat diet (HF-rats). The results
      show that inhibition of fatty acid oxidation by MA, reflected by a decrease in
      plasma beta-hydroxybutyrate, elicited eating in the HF-rats and that the eating
      response was not associated with a decrease in circulating glucose. The effect of
      MA on food intake was tested in two different substrains (Zur:SD and Ico:OFA SD)
      of Sprague-Dawley rats. The threshold dose of MA for eliciting eating was much
      higher in Zur:SD (between 800 and 1,600 micromol/kg) in comparison to Ico:OFA SD
      rats (between 200 and 400 micromol/kg). At a high dose of MA (1,200 micromol/kg),
      but not at a low dose (400 micromol/kg) the feeding response in the Ico:OFA SD
      rats was associated with hyperglycemia due to an increase in glycogenolysis.
      Unlike in Zur:SD, in Ico:OFA SD rats the higher doses of MA (800 and 1,200
      micromol/kg but not 400 micromol/kg) produced a long-term suppression of feeding,
      which partly might be causally related to the observed inhibitory effect of MA on
      gastric emptying. The present results indicate that glucose deprivation does not
      contribute to feeding elicited by MA-induced inhibition of fatty acid oxidation
      in rats fed a carbohydrate-free, high-fat diet.

PMID- 11842893
TI  - Improving mental health through nutrition: the future.
AB  - Tell me what you eat, and I will tell you what you are (Anthelme Brillat
      Savarin). When I behold a fashionable table set out in all its magnificence, I
      fancy that I see gouts and dropsies, fever and lethargies, with other innumerable
      distempers, lying in ambuscade among the dishes. Nature delights in the most
      plain and simple diet. Every animal, but man, keeps to one dish. Herbs are the
      food of this species, fish of that, and flesh of a third. Man falls upon
      everything that comes in his way; not the smallest fruit or excrescence of the
      earth, scarce a berry or a mushroom can escape him (Joseph Addison). The
      pleasures of the palate deal with us like the Egyptians thieves, who strangle
      those whom they embrace (Seneca). Let food be your medicine and medicine be your
      food (Hippocrates).

PMID- 11842894
TI  - Increased protein intake during recovery from zinc deficiency is accompanied by
      alterations in hypothalamic growth hormone releasing factor and somatostatin.
AB  - To determine if alterations in growth hormone releasing factor (GRF) and
      somatostatin (SRIF) occur during recovery from zinc deficiency and to examine the
      relationship between these peptides and the increased protein intake observed
      during zinc repletion, both the hypothalamic release and mRNA levels of GRF and
      SRIF were measured during zinc deficiency and zinc repletion. Groups of male rats
      (n = 4-8 each) were provided 3-choice macronutrient diets made either zinc
      adequate (Zn+) or deficient (Zn-; 30 vs. 1 mg Zn/kg diet). Pair fed, calorie
      restricted (PF) rats were also maintained. After 28 days, Zn- rats were repleted
      with Zn+ diets for 2 days and one PF group was allowed free access to the same
      Zn+ diets for 2 days. Additionally, groups of Zn- and PF rats were repleted 2
      days with Zn+ carbohydrate and fat diets but no protein. Hypothalamic GRF and
      SRIF release was measured in vitro. Basal GRF secretion was not significantly
      different between Zn-, PF, or Zn+ groups although there was a significant
      increase (P<0.05) during zinc repletion. PF and Zn- rats repleted 2 days with
      diets devoid of protein had highest GRF secretion (P<0.01) compared to other
      groups. There were no differences in GRF mRNA levels among groups. Basal SRIF
      secretion was significantly lower in Zn- and PF groups compared to Zn+, and SRIF
      mRNA levels were significantly higher in zinc repleted groups compared to Zn-.
      These results demonstrate that during zinc repletion, GRF and SRIF secretion and
      SRIF gene expression are altered concomitantly with protein intake. The present
      data support involvement of GRF in protein intake changes during zinc repletion.

PMID- 11842895
TI  - Growth hormone-releasing factor affects macronutrient intake during the anabolic
      phase of zinc repletion: total hypothalamic growth hormone-releasing factor
      content and growth hormone-releasing factor immunoneutralization during zinc
      repletion.
AB  - Growth hormone-releasing factor (GRF) is thought to perform two distinct
      functions within the brain. GRF synthesized in the median eminence (ME)
      stimulates the release of growth hormone (GH) from the pituitary, while GRF in
      the suprachiasmatic nucleus and median preoptic area (SCN/MPOA) may stimulate
      selection of dietary protein. These two functions may be coupled to regulate and
      enhance growth. During zinc repletion, a period characterized by increased
      protein intake and accelerated growth, we examined this coupling by measuring GRF
      peptide content in hypothalamic sites and neutralizing GRF function by infusing
      anti-GRF antibody into the hypothalamus during zinc repletion. Total GRF content
      and GRF content in the ME and SCN/MPOA were decreased in zinc-deficient (Zn-)
      rats compared to zinc-adequate (Zn+) rats (P < 0.05). There were no differences
      in GRF content during zinc repletion in either nuclei. Subsequently, we
      investigated the macronutrient feeding patterns of rats chronically infused with
      anti-GRF IgG into the lateral ventricle of the brain during zinc repletion. All
      Zn- and Zn+ rats administered anti-GRF IgG exhibited a reduction in protein
      intake during zinc repletion. The Zn- rats receiving anti-GRF-IgG consumed equal
      amounts of total diet compared to those receiving vehicle during the repletion
      period however they consumed less carbohydrate (P < 0.05) and considerably more
      fat (P < 0.02). There were no significant differences in carbohydrate or fat
      intake in Zn+ rats receiving anti-GRF antibody. These results suggest that GRF
      likely directs protein intake during normal growth, but may interact with
      additional appetite-controlling neuropeptides during zinc repletion.

PMID- 11842896
TI  - Dose dependent changes in cognitive performance and mood following acute
      administration of Ginseng to healthy young volunteers.
AB  - Recent evidence suggests that chronic administration of Ginseng can improve
      cognitive performance in animals and in humans. No previous study has examined
      the possibility of cognitive effects following single doses of Ginseng in healthy
      adults. The present study investigated whether acute administration of Ginseng
      (G115, Pharmaton SA) had any consistent effect on mood and four aspects of
      cognitive performance ("Quality of Memory", "Speed of Memory", "Quality of
      Attention" and "Speed of Attention") that can be derived by factor analysis of
      the Cognitive Drug Research computerised assessment battery. The study followed a
      placebo-controlled, double-blind, balanced, crossover design. Twenty healthy
      young adult volunteers received 200, 400, and 600 mg of G115, and a matching
      placebo, in counterbalanced order, with a 7 day wash-out period between
      treatments. Following a baseline cognitive assessment, further test sessions took
      place 1, 2.5, 4 and 6 h after the day's treatment. The most striking result was a
      significant improvement in "Quality of Memory" and the associated "Secondary
      Memory" factor at all time points following 400 mg of Ginseng. Both the 200 and
      600 mg doses were associated with a significant decrement of the "Speed of
      Attention" factor at later testing times only. Subjective ratings of alertness
      were also reduced 6 h following the two lowest doses. To the best of our
      knowledge this represents the first demonstration of a modulation of mood and
      cognitive performance by acute administration of Ginseng.

PMID- 11842897
TI  - Recovery of long-term maternal behavioral deficiencies of neonatally underfed
      rats by early sensory stimulation: effects of successive parturitions.
AB  - The study examines the effects of two paradigms of neonatal food deprivation
      (daily mother-litter separation, Experiment 1 or nipple-ligation of mothers,
      Experiment 2) associated or not to early sensory stimulation (daily handling or
      the exposure to an enriched sensory environment) during the pre-weaning period of
      Wistar strain female rats. The effects of experimental manipulations were
      evaluated by measuring the nest building, retrieving latencies and nursing time
      of adult dams along three successive parturitions. Undernourished dams of
      Experiment 1, showed significant alterations in maternal responsiveness in the
      first delivery, which were attenuated by the maternal experience of two
      additional parturitions. Moreover, maternal alterations were importantly
      compensated by the association to early sensory stimulation (except nest
      building). Underfed mothers of Experiment 2 exhibited less alterations of the
      maternal response during the first parturition, and these were ameliorated by the
      maternal experience of successive parturitions. Additionally, complete recovery
      of maternal responsiveness alterations was obtained when sensory stimulation was
      associated to the maternal experience. Data suggest differential vulnerability to
      neonatal food and sensory deprivation of the neural mechanisms underlying
      maternal performance.

PMID- 11842898
TI  - Role of neuropeptide Y and galanin in high altitude induced anorexia in rats.
AB  - Anorexia causing weight loss at high altitude (HA) is a major problem.
      Neuropeptide Y (NPY) and galanin are considered to have appetite regulatory
      function. The present study was therefore undertaken to investigate the changes
      in these two peptides at simulated HA and its possible role in anorexia. Male
      Sprague-Dawley rats (n = 8 in each group) were exposed to simulated HA (7620 m)
      for 1, 7, 14 and 21 days for 6 h a day and to an altitude of 6,096 m for 72 h to
      study the effect of intermittent and continuous exposure, respectively. NPY and
      galanin levels were estimated in different brain parts and plasma of exposed and
      unexposed control animals. Significant reduction in food intake was observed in
      rats during both intermittent as well as continuous exposure. In case of 72 h
      continuous exposure severe reduction in food intake was observed (73.2%) with
      reduction in body mass (approximately 29.7g/rat in 48h). Hypothalamic NPY levels
      were decreased by 54.7, 35.0 and 15.4% in 1, 7, and 14 days, respectively, in
      case of intermittent exposure to HA. However in case of 72 h HA exposure no
      significant change in hypothalamic and circulating NPY levels were observed.
      Plasma galanin levels were decreased in both intermittent and 72 h continuous HA
      exposed rats. Hypothalamic galanin levels were also decreased in 72h exposed
      rats. The changes in levels of these peptides may be responsible for anorexia at
      HA.

PMID- 11842899
TI  - EMG and pain severity evaluation in patients with TMD using two different
      occlusal devices.
AB  - PURPOSE: The purpose of this study was to compare the electromyographic (EMG)
      activity level and signs and symptoms in patients with myogenous
      temporomandibular disorders (TMD) treated with two different types of occlusal
      devices. MATERIALS AND METHODS: Eleven TMD patients were treated with maxillary
      occlusal devices. The first group received a flat-plane stabilization occlusal
      device, while the second group received an anatomic occlusal device that
      maintained the anatomy of the original occlusal surfaces. The severity of signs
      and symptoms and the masseter EMG activity were recorded and evaluated before
      treatment and at 72 hours, 2 weeks, and 4 weeks following the delivery of the
      occlusal device. EMG activity was measured during maximum clenching and during
      chewing on the right and left sides. The EMG was also recorded for seven normal
      subjects as a control group. RESULTS: All patients showed reduction of reported
      and clinically found muscle pain, with no statistically significant differences
      between the two groups. A reduction in the EMG activity level at maximum
      clenching was seen in both patient groups, but was significant only with the
      anatomic occlusal device. Mean EMG activity during chewing was highly variable
      within and between groups. CONCLUSION: The subjective and objective improvements
      with both types of occlusal devices suggest that either type of occlusal device
      can be beneficial to TMD patients.

PMID- 11842900
TI  - Flexural properties of the bulk fiber-reinforced composite DC-tell used in fixed
      partial dentures.
AB  - PURPOSE: The aim of this study was to measure the flexural properties of fiber
      reinforced composite (FRC) used in frameworks of fixed partial dentures. In
      addition, the influence of water storage on the properties was determined.
      MATERIALS AND METHODS: Rhombic test specimens for four groups were milled from
      bulk FRC material DC-Tell. The test specimens of the first group were stored and
      tested dry. In the second group, the test specimens were water stored for 3
      months at 37 +/- 1 degrees C and tested in water. The specimens of the third
      group were also water stored, but they were tested dry at room temperature. Water
      stored test specimens of the fourth group were dehydrated and tested dry at room
      temperature. A three-point bending test was used to measure the flexural
      properties. The quantity of glass fibers in the test specimens was determined by
      combustion analysis. Water uptake was calculated after 3 months of water
      immersion. The direction and length of fibers were examined, and elemental
      composition was determined. RESULTS: Water storage decreased the flexural
      strength by 66% and flexural modulus by 60%. After dehydration, the flexural
      strength did not recover to the same level as the flexural strength of the dry
      group specimens. The fiber content was 38% by volume. Water uptake was 3 wt%. The
      reinforcement of DC-Tell was short fibers in random orientation, and the
      elemental composition of fibers was similar to that of E-glass. CONCLUSION: Water
      storage decreases the flexural properties of the bulk fiber-reinforced composite
      DC-Tell. This may restrict the use of DC-Tell as a framework of crowns and
      bridges in the oral cavity in the long term.

PMID- 11842901
TI  - The outcome of implant overdentures from a prosthodontic perspective: proposal
      for a classification protocol.
AB  - PURPOSE: This article proposes a classification protocol for reporting the
      outcome of implant overdentures. MATERIALS AND METHODS: Review of the literature
      pertaining to postinsertion prosthodontic procedures for maxillary and mandibular
      implant overdentures revealed a wide range in the terminology used and methods of
      reporting outcome, usually as a result of the use of varying designs among
      different implant systems. A need for comparative evaluation of the prosthodontic
      success of implant overdentures was identified. RESULTS: An existing
      classification protocol for implant-fixed prostheses containing six objectively
      defined fields was modified for implant overdentures. This new protocol, which
      also uses the descriptive fields of success, survival, unknown, dead, and
      retreatment (repair or failure), provides a method whereby postinsertion
      prosthodontic procedures and subsequent time to retreatment can be quantified
      regardless of design, method of attachment, or implant system. A ratio method for
      identifying prosthodontic treatment cost effectiveness of implant overdentures is
      included. CONCLUSION: This protocol could assist clinicians in their choices of
      implant overdenture therapy by providing accurate comparisons of varying implant
      overdenture systems and designs, and by identifying prosthodontic treatment cost
      effectiveness.

PMID- 11842902
TI  - The flexural properties of fiber-reinforced composite with light-polymerized
      polymer matrix.
AB  - PURPOSE: The aim of this study was to measure the flexural strength and the
      elastic modulus of composite resin with and without reinforcing fibers and to
      evaluate the reinforcing effect of various fibers. MATERIALS AND METHODS: A
      polyethylene fiber (Ribbond), a polyaramid fiber (Fibreflex), and three glass
      fibers (FibreKor, GlasSpan, Vectris) were used to reinforce composite resins. The
      flexural strength and elastic modulus of specimens in the three-point bending
      mode were measured using a universal testing machine at a cross-head speed of 1
      mm/min after storage in water at 37 degrees C for 24 hours. All tests were
      carried out in a water bath at 37 degrees C. The data were analyzed using
      analysis of variance and the Sheffe test at P= 0.05. After testing, the fractured
      surface was evaluated using a scanning electron microscope at 50x, 500x, and
      3,000x magnifications. RESULTS: Yield flexural strengths of nonreinforced resins
      were 48 to 56 MPa, and those of reinforced resins were 56 to 134 MPa. Ultimate
      flexural strengths of nonreinforced specimens were 96 to 119 MPa, and those of
      reinforced ones were 203 to 386 MPa. Elastic modulus of nonreinforced resin was 6
      to 9 GPa, and fiber reinforcing increased the value to 9 to 15 GPa, while it had
      no effect in Ribbond. CONCLUSION: Most of the fibers used in this study increased
      both yield and ultimate flexural strengths of composite resins, with the
      exception of the yield strength of Vectris. GlasSpan, Fibreflex, and FibreKor
      were effective in reinforcing elastic modulus, while Ribbond had no effect on it.
      Unidirectional glass fibers and polyaramid fiber were effective in reinforcing
      both flexural strength and elastic modulus of composite resin.

PMID- 11842903
TI  - Microstructures of brazings and welds using grade 2 commercially pure titanium.
AB  - PURPOSE: Microstructural analyses of commercially pure titanium (CpTi) are
      scarce. The present report presents the micrographs, fractographs, elemental
      characteristics, and hardness profiles of brazed joints and weldments using
      machined rods of CpTi. MATERIALS AND METHODS: CpTi rods were joined using four
      techniques: laser welding, electric-arc welding, electron-beam welding, and gold-
      and Ti-filler brazing. The specimens were then subjected to tensile and fatigue
      loading. After sectioning and patterning, optical micrographs of intact joints
      were obtained. Fractured surfaces were investigated using scanning electron
      microscopy (SEM). The joint's composition was determined by SEM-energy dispersive
      x-ray analysis. Hardness was determined at specific locations using a
      microindenter. RESULTS: While laser welding left the parent metal's equiaxed
      structure fairly intact, electric-arc welding, electron-beam welding, and brazing
      created a heat-affected zone in the vicinity of the joint. The extent and
      characteristics of the heat-affected zone depended on the amount of heat
      transferred to the specimens. In this respect, brazing essentially increased
      grain size and altered their shape. Electron-beam welding augmented this
      phenomenon, yielding grains that encompassed the full diameter of the joint.
      Electric-arc welding disrupted the granular pattern and generated highly
      lamellar/acicular structures. CONCLUSION: Hardness was not a good indicator of
      mechanical resistance, nor was the joint's structural continuity with the parent
      substrate. Still, acicular microstructures were characterized by a peculiar
      behavior in that such joints were highly resistant to tensile stresses while
      their fatigue strength ranged among the lowest of the joints tested.

PMID- 11842904
TI  - Growth of Candida species on commercial denture adhesives in vitro.
AB  - PURPOSE: Although denture adhesives are widely used by the elderly, it is unknown
      whether denture adhesives support microbial growth. Therefore, we investigated
      the growth of Candida species on six commercial denture adhesives. MATERIALS AND
      METHODS: The growth of a single isolate of C albicans and C tropicalis on six
      commercial denture adhesives was investigated by monitoring pH changes in growth
      media. RESULTS: In the preliminary study, the effect of each product on the pH
      value of the medium was examined; a single product itself significantly reduced
      the pH of medium below 5.0. When the yeast was grown on the materials, the pH
      changes in the media varied depending on the adhesive materials and, to a greater
      or lesser extent, on whether they showed antifungal activity. Two products
      (Cushion Collect and Collect Soft A) significantly suppressed C albicans growth
      (P < 0.01), and one product (Collect Soft A) effectively reduced C tropicalis
      growth (P < 0.01). CONCLUSION: Our results suggest that denture adhesives possess
      antifungal activity to a greater or lesser degree. However, one product caused
      the reduction of pH below 5.0. Thus, in the daily use of denture adhesives,
      attention should be paid to both the materials and their microbiologic
      properties.

PMID- 11842905
TI  - Evaluation of research and the IJP award.

PMID- 11842906
TI  - The effect of oscillation and low seating forces on pulpward pressure
      transmission and seating during crown cementation: a laboratory study.
AB  - PURPOSE: This study investigated the effects of low seating force (5 N) with and
      without oscillation on pulpward pressure transmission during crown cementation.
      MATERIALS AND METHODS: Thirty human premolars received standardized complete
      crown preparations. They were randomly allocated into three experimental groups
      of ten: group 1 = 100-N static load; group 2 = 5-N static load; and group 3 = 5-N
      load with oscillation. Crowns were constructed of base-metal alloy and attached
      to a purpose-built loading device. Pulpal pressures were recorded using a 0- to
      104-kPa pressure transducer that was connected via the sectioned root of the
      premolar to the pulp chamber, which was perfused with saline driven by nitrogen
      gas at 83 kPa until a steady rate was achieved. The crowns were cemented using
      zinc phosphate cement, and postcementation elevations were measured with a linear
      variable differential transformer. An amalgam condenser provided oscillation for
      1 minute. RESULTS: The pulpal pressures were: group 1 = 455 Pa; group 2 = 26 Pa;
      and group 3 = 76 Pa. The postcementation crown elevations were: group 1 = -48
      microm; group 2 = 362 microm; and group 3 = 26 microm. CONCLUSION: Acceptable
      crown seating can be obtained using low force (5 N) combined with oscillation,
      and lower pressure pulses are generated compared to using high force (100 N)
      alone.

PMID- 11842909
TI  - Comparison of deformation by stereophotogrammetry of various kinds of major
      connectors in maxillary Kennedy Class I removable partial dentures.
AB  - PURPOSE: Major connectors must be rigid to perform their functions with maximum
      efficacy. This study investigated the deformation of four major connectors for
      maxillary Kennedy Class I removable partial dentures. MATERIALS AND METHODS: The
      designs were palatal plate, U-shaped plate, palatal strap, and anteroposterior
      bar. The deformation properties of major connectors were comparatively analyzed
      by two methods. In the photogrammetric part, a stereometric camera, Avipan-100
      glass films, and an analytic apparatus were used. A computerized hydraulic
      machine was programmed to load the eight test dentures at 4-Hz frequency under a
      vertical load of 100 kg and a maximum of 300,000 cycles. The fluorescence
      penetrant liquid inspection test was used to detect the surface microcracks.
      RESULTS: The anteroposterior bar showed the least deformation. The other
      connectors, ranked in increasing order for the amount of deformation, were the U
      shaped plate, the palatal strap, and the palatal plate. There were no microcracks
      in the U-shaped plate and the anteroposterior bar designs. CONCLUSION:
      Anteroposterior bar major connectors showed the least deformation among the
      maxillary major connector types tested. Microscopic cracks were seen in major
      connectors showing the highest degree of deformation and located at the depth of
      the hard palate.

PMID- 11842907
TI  - Survival rate and fracture strength of endodontically treated maxillary incisors
      with moderate defects restored with different post-and-core systems: an in vitro
      study.
AB  - PURPOSE: This study compares the survival rate and fracture strength of
      endodontically treated maxillary incisors with moderate coronal defects restored
      with different post-and-core systems after exposure to an artificial mouth.
      MATERIALS AND METHODS: Sixty-four caries-free human maxillary central incisors
      were selected for standardized size and quality, endodontically treated, and
      decoronated 2 mm coronal to the cementoenamel junction. Group 1 was restored with
      titanium posts and composite cores, group 2 received zirconia posts and a
      composite core, and in group 3 zirconia posts with a heat-pressed ceramic core
      were used. Teeth restored with cast posts and cores served as controls. All teeth
      were prepared and restored with complete cast crowns. All samples were exposed to
      1.2 million cycles in a computer-controlled chewing simulator with simultaneous
      thermocycling. In addition, the samples were loaded until fracture in a static
      testing device. RESULTS: The survival rates of the different groups were: 94% for
      titanium/composite, 63% for zirconia/composite, 100% for the all-ceramic post and
      core, and 94% for the cast post and core. The following mean fracture strengths
      were obtained: titanium/composite = 425 +/- 155 N, zirconia/composite = 202 +/-
      212 N, zirconia/ceramic = 378 +/- 64 N, cast post and core = 426 +/- 178 N. The
      lower fracture load in the group with zirconia posts and composite cores was
      statistically significant. The use of zirconia posts resulted in fewer oblique
      root fractures. CONCLUSION: Prefabricated titanium posts with composite cores,
      zirconia posts with heat-pressed ceramic cores, and cast posts and cores yield
      comparable survival rates and fracture strengths for the restoration of crowned
      maxillary incisors with moderate coronal defects. Survival rates and fracture
      strengths for zirconia posts with composite cores are significantly lower, so
      this combination cannot be recommended for clinical use.

PMID- 11842908
TI  - Severity, distribution, and correlates of occlusal tooth wear in a sample of
      Mexican-American and European-American adults.
AB  - PURPOSE: The objective of this study was to determine the severity, distribution,
      and correlates of tooth wear in a sample of Mexican-American and European
      American adults drawn from a community-based longitudinal aging study on oral
      health. MATERIALS AND METHODS: The maxillary teeth of 71 subjects enrolled in a
      longitudinal aging study were assessed using a previously introduced five-point
      (0 to 4) ordinal scoring system in which each tooth is given a score describing
      the severity of wear. The tooth wear scores were compared with data concerning
      demographic factors, functional/parafunctional habits, soft drink consumption,
      and bite force measurements to determine specific correlates of tooth wear.
      RESULTS: The mean wear score for all teeth was 1.50 on the five-point scale.
      There was a significant difference between the mean wear score of anterior teeth
      (1.85) and posterior teeth (1.17). Bivariate analyses detected a moderate degree
      of correlation between maxillary tooth wear and age and bite force. Maxillary
      tooth wear was significantly greater in males and in subjects with reported teeth
      clenching/grinding. Multivariate analyses revealed that age, gender, bite force,
      self-reported teeth clenching/grinding, and number of daily meals/snacks had
      significant correlations with maxillary tooth wear. CONCLUSION: The overall
      severity of maxillary tooth wear in this sample of Mexican-American and European
      American adults was low, with anterior teeth having a greater degree of wear than
      posterior teeth. Age, gender, bite force, teeth clenching/grinding, and number of
      daily meals/snacks are potential factors that may have contributed to tooth wear
      in the study sample.

PMID- 11842912
TI  - One-piece castings in fixed prosthodontics.

PMID- 11842910
TI  - Correlation between quality of life and denture satisfaction in elderly complete
      denture wearers.
AB  - PURPOSE: This study was done to clarify the correlation between the quality of
      life (QOL), defined as overall satisfaction with daily life, and denture
      satisfaction in elderly complete denture wearers. MATERIALS AND METHODS: A new
      method for quantifying overall satisfaction with daily life (QOL) among 2,079
      elderly people (age > or = 65 years) was developed by evaluating the contribution
      of 13 factors (eating, health problems, daily exercise, fatigue, sleep quality,
      smooth communication, physical comfort, aging, loneliness, job and hobbies,
      meaningfulness, social life, and economic problems) to overall daily life
      satisfaction by a multiple regression analysis. Then, correlation between the QOL
      and denture satisfaction was analyzed by the regression model in 84 randomly
      selected complete denture wearers from the above population. RESULTS:
      Quantification of the QOL was completed by converting category scores to integers
      between 0 and 100 for eight highly correlated factors (eating, smooth
      communication, physical comfort, loneliness, job and hobbies, meaningfulness,
      social life, and economic problems) to overall satisfaction with daily life (P <
      0.01). Significant positive correlation was found between the QOL score and
      denture satisfaction score (P < 0.05). CONCLUSION: Edentulous elderly people who
      are well satisfied with their daily lives are also satisfied with their complete
      dentures.

PMID- 11842911
TI  - Short-term clinical evaluation of inlay and onlay restorations made with a
      ceromer.
AB  - PURPOSE: This prospective clinical trial evaluated the clinical acceptability of
      a new material, ceromer, used for inlay and onlay restorations in single- or
      multisurface cavities of posterior teeth. MATERIALS AND METHODS: Forty-three
      Targis inlay and onlay restorations were placed in 25 patients and evaluated
      using the United States Public Health Service criteria. The laboratory work was
      conducted by three dental technicians according to the manufacturer's
      recommendations. Twenty-five restorations were luted with Syntac bonding system
      and Variolink II, and 18 were luted with Scotchbond Multi Purpose and Opal Luting
      Composite. The recalls were done at 6, 12, and 18 months. Restorations were
      evaluated for six parameters and scored as ideal (A), clinically acceptable (B),
      or clinically unacceptable (C). RESULTS: Indirect restorations received, after 18
      months, scores of A at the following rates: color match 77%; marginal
      discoloration 93%; secondary caries 100%; anatomic form 93%; and marginal
      integrity 95%. For these parameters, statistical analysis indicated no
      significant differences at baseline and after 18 months. Postoperative
      hypersensitivity was reported by seven patients at baseline, but it decreased and
      there was no hypersensitivity at 12- and 18-month follow-ups. CONCLUSION: Over an
      18-month period the Targis restorative system yielded good clinical service.

PMID- 11842914
TI  - Is age-induced decline in immune response associated with hypothalamic glutamate
      receptor density and dietary protein?
AB  - Manipulation of dietary protein has been found to be the most useful dictator in
      the age-associated decline of neuroimmune activity in mammals. In the present
      study, we sought to clarify the effect of dietary protein on age-induced
      alterations of hypothalamic glutamatergic activity and immune response. The
      hypothalamic glutamatergic activity and immune response were found to increase
      and decrease, respectively, with the increase in age of rats from young (3
      months) to old (18 months) maintained with normal (20%) protein diet. Intake of
      low (5%) protein diet (LPD) and high (40%) protein diet (HPD) under short-term
      period (7 days) failed to alter the age-associated loss of immune response and
      increase in hypothalamic glutamatergic activity. However, long-term (30 days)
      supplementation of LPD retarded the age-induced decline in immune response and
      increase in hypothalamic glutamatergic activity, whereas, HPD consumption under
      similar condition potentiated the age-related immunosuppression and increase in
      hypothalamic glutamatergic activity. These results suggest that (a) the age
      associated immunosuppression may be inversely related to the hypothalamic
      glutamatergic activity and (b) consumption of diets having variable quantity of
      protein without variation of calorie content modulates immune response and
      hypothalamic glutamatergic activity depending upon age and duration of dietary
      supplementation.

PMID- 11842915
TI  - Neuroprotective effects of pyridoxal phosphate and pyridoxal against ischemia in
      monkeys.
AB  - Previously, in monkeys undergoing 20 min whole brain ischemia we demonstrated
      that the activated calpain-induced lysosomal disruption with the resultant
      leakage of cathepsins B and L, causes neuronal death in the cornu Ammonis (CA) 1
      sector on day 5. Selective cathepsin inhibitors significantly protected ischemic
      CA1 neurons from delayed necrosis. Recently, pyridoxal phosphate (PLP) and
      pyridoxal (hydrochloride) (PL) were demonstrated to inhibit cathepsins B and L in
      vitro, because the active aldehyde at position 4 of the pyridine ring has an
      affinity for the active site -SH of cysteine residues of cathepsins. Here, we
      studied whether PLP and PL can, in vivo, protect monkey CA1 neurons from ischemic
      insult. In monkeys undergoing 20 min whole brain ischemia, 15 mg/kg body
      weight/day of drugs were intravenously injected for 10 days before and after the
      ischemic insult. Histological analysis of the surviving CA1 neurons was done
      using the hippocampus resected on day 5 after ischemia. For PLP or PL,
      approximately 17% (P = 0.0639) or 54% (P < 0.0001) of the total population (100%)
      of control CA1 neurons were, respectively, saved from the ischemia-induced
      neuronal death, showing a remarkable contrast to the surviving neurons
      (approximately 3.9%) in non-treated monkeys. These data suggested that PL
      (perhaps PLP intracellularly) is useful as a novel neuroprotectant in primates.

PMID- 11842913
TI  - Influence of posts and cores on light transmission through different all-ceramic
      crowns: spectrophotometric and clinical evaluation.
AB  - PURPOSE: The influence of different types of posts and cores on light
      transmission through all-ceramic crowns was assessed by spectrophotometric
      analysis and clinical evaluation. MATERIALS AND METHODS: Three extracted natural
      teeth were replicated in acrylic resin, with roots prepared to receive
      standardized posts and cores. Using a silicone impression material as a template,
      various prosthodontic reconstructions were obtained by combining four types of
      posts and cores (polished and matte-finished gold alloy, all-ceramic, and
      ceramized metal alloy) and three types of all-ceramic crowns (IPS-Empress 2
      surface-colored, IPS-Empress 2 stratified, and In-Ceram). The spectrophotometric
      analysis was performed in the dark at 25 degrees C. The teeth were backlit with
      an incandescent lamp at the color temperature of A illuminant and shielded to
      avoid spurious light entering the spectrophotometer. The transmitted light was
      analyzed in terms of luminance at four points of the sample surface (cervical,
      middle, incisal, and proximal). Twelve measurements were performed for the
      natural teeth, and 144 were performed for the artificial teeth. RESULTS: Natural
      teeth had the highest luminance. Among all-ceramic crowns, surface-colored IPS
      Empress 2 had the highest luminance, and stratified IPS-Empress 2 had the lowest.
      Regarding posts and cores, the luminance was highest with the all ceramic, lower
      with the ceramized and the polished gold alloy (which had very similar
      luminance), and lowest with the matte-finished gold alloy. No significant
      difference among prosthodontic combinations was detected under clinical
      observation. CONCLUSION: The surface-colored glass ceramic (IPS-Empress 2) was
      the most translucent crown. At the standard crown thickness used, there were
      small, significant spectrophotometric, but not clinical, differences among the
      combinations tested. These findings show no esthetic contraindications for the
      use of polished gold alloy posts and cores with all-ceramic crowns.

PMID- 11842916
TI  - Differential, dose dependent changes in cognitive performance following acute
      administration of a Ginkgo biloba/Panax ginseng combination to healthy young
      volunteers.
AB  - We have previously shown differential cognitive improvements following single
      doses of Ginkgo biloba and of Ginseng. There is also evidence that chronic
      administration of a combination of standardised extracts of Ginkgo biloba and
      Panax ginseng may improve aspects of cognitive performance both in pathological
      populations and the healthy middle aged. No investigation has thus far looked
      either at the cognitive effects of single doses of such a combination, nor the
      effects of the combination on healthy young volunteers. The present study
      investigated whether acute administration of a combination of standardised
      extracts of Ginkgo biloba (GK501, Pharmaton SA) and Ginseng (G115, Pharmaton SA)
      had any consistent effect on mood and aspects of cognitive performance ("quality
      of memory", "secondary memory", "working memory", "speed of memory", "quality of
      attention" and "speed of attention") that can be derived by factor analysis of
      the cognitive drug research computerised assessment battery. The study followed a
      placebo-controlled, double blind, balanced, crossover design. Twenty healthy
      young adult volunteers received 320, 640, and 960 mg of the combination, and a
      matching placebo, in an order dictated by random allocation to a Latin square,
      and with a seven-day wash-out period between treatments. Following a baseline
      cognitive assessment, further test sessions took place 1, 2.5,4 and 6 h after the
      day's treatment. The most striking result was a dose-dependent improvement in
      performance on the "quality of memory" factor for the highest dose. Further
      analysis revealed that this effect was differentially targeted at the secondary
      memory rather than the working memory component. There was also a dose dependent
      decrement in performance of the "speed of attention" factor for both the 320 and
      640 mg doses. These results are discussed in the context of previous findings
      within this series of studies.

PMID- 11842917
TI  - Plasma Trp/LNAA ratio increases during chronic ingestion of an alpha-lactalbumin
      diet in rats.
AB  - Brain serotonin synthesis depends on the uptake of its precursor, tryptophan
      (Trp), and is correlated to the plasma ratio of Trp to large neutral amino acids
      (LNAA) which compete for the same transporter system in the brain. As the plasma
      Trp/LNAA ratio decreases when the dietary protein content exceeds 5%, we tested
      whether a diet containing 17% of a Trp-rich protein, namely alpha-lactalbumin
      (LAC), might increase the plasma Trp/LNAA ratio over a long period. Blood samples
      were obtained at different days (-1, 3, 6 and 9) from rats receiving either a LAC
      or casein (CAS) diet, and plasma amino acids and insulin concentrations were
      determined. The increase in plasma Trp concentration was much higher during the
      LAC diet (49 vs 26%; P<0.001), while the plasma LNAA concentration remained
      fairly constant. Consequently, the plasma Trp/LNAA ratio increased by 40% during
      the LAC diet while it decreased by 15% during the CAS diet (P<0.001). The above
      results were not related to plasma insulin concentration differences during these
      diets. These data suggest that a balanced diet containing a natural Trp rich
      protein increases the plasma Trp/LNAA ratio over a long period, leading to a
      probable increase in brain serotonin activity.

PMID- 11842918
TI  - Specificity of Ca2+ signaling in polarized cells.

PMID- 11842919
TI  - Salivary histatin 5 and its similarities to the other antimicrobial proteins in
      human saliva.
AB  - Non-immune salivary proteins--including lactoperoxidase, lysozyme, lactoferrin,
      and histatins--are key components of the innate host defense system in the oral
      cavity. Many antimicrobial proteins contain multiple functional domains, with the
      result that one protein may have more than one mechanism of antimicrobial
      activity. These domains may be separated by proteolytic cleavage, creating
      smaller proteins with functional antimicrobial activity in saliva as described
      for lysozyme, lactoferrin, and histatins. These small cationic proteins then
      exert cytotoxic activity to oral bacteria and fungi. Salivary histatin 5
      initiates killing of C. albicans through binding to yeast membrane proteins and
      non-lytic release of cellular ATP. Extracellular ATP may then activate fungal ATP
      receptors to induce ultimate cell death. This mechanism for fungal cytotoxicity
      may be shared by other antimicrobial cationic proteins. Microbicidal domains of
      salivary and host innate proteins should be considered as potential therapeutic
      agents in the oral cavity.

PMID- 11842920
TI  - Saliva and dental pellicle--a review.

PMID- 11842921
TI  - Saliva and dental plaque.
AB  - Dental plaque is being redefined as oral biofilm. Diverse overlapping microbial
      consortia are present on all oral tissues. Biofilms are structured, displaying
      features like channels and projections. Constituent species switch back and forth
      between sessile and planktonic phases. Saliva is the medium for planktonic
      suspension. Several major functions can be defined for saliva in relation to oral
      biofilm. It serves as a medium for transporting planktonic bacteria within and
      between mouths. Bacteria in transit may be vulnerable to negative selection.
      Salivary agglutinins may prevent reattachment to surfaces. Killing by
      antimicrobial proteins may lead to attachment of dead cells. Salivary proteins
      form conditioning films on all oral surfaces. This contributes to positive
      selection for microbial adherence. Saliva carries chemical messengers which allow
      live adherent cells to sense a critical density of conspecifics. Growth begins,
      and thick biofilms may become resistant to antimicrobial substances. Salivary
      macromolecules may be catabolized, but salivary flow also may clear dietary
      substrates. Salivary proteins act in ways that benefit both host and microbe. All
      have multiple functions, and many do the same job. They form heterotypic
      complexes, which may exist in large micelle-like structures. These issues make it
      useful to compare subjects whose saliva functions differently. We have developed
      a simultaneous assay for aggregation, killing, live adherence, and dead adherence
      of oral species. Screening of 149 subjects has defined high killing/low
      adherence, low killing/high adherence, high killing/high adherence, and low
      killing/low adherence groups. These will be evaluated for differences in their
      flora.

PMID- 11842923
TI  - Xerostomia and hyposalivation.
AB  - Dry mouth must not be considered a trivial problem in the population, since it
      constitutes a phenomenon with many aspects relative to oral function as well as
      quality of life. Up until today, no global consensus has been reached with regard
      to the terminology of dry mouth, creating a substantial problem for research,
      education, diagnosis, and therapy. In this report, salivary gland hypofunction
      has been selected as the overarching term for subjective symptoms and objective
      signs of dry mouth. Its different aspects--xerostomia, hyposalivation, and
      altered saliva composition--are reviewed with respect to prevalence, diagnosis,
      and etiology. It is concluded that these aspects of salivary gland hypofunction
      are separate entities, which in many respects are interrelated, constituting not
      merely a dental but also a medical and social concern.

PMID- 11842922
TI  - Saliva and dental caries.
AB  - Caries is a unique multifactorial infectious disease. Our understanding of
      etiological factors, the progress of the disease, and the effectiveness of
      prophylactic procedures have led us to believe that we understand the disease.
      However, we still have too few answers to many questions: "Why can we not predict
      who will get the disease?" "Why do we not become immunized?" "How much saliva is
      enough?" or "Which salivary components are protective?" and "Which salivary
      components predispose for caries?" It is generally accepted, however, that saliva
      secretion and salivary components secreted in saliva are important for dental
      health. The final result, "caries to be or not to be", is a complex phenomenon
      involving internal defense factors, such as saliva, tooth surface morphology,
      general health, and nutritional and hormonal status, and a number of external
      factors-for example, diet, the microbial flora colonizing the teeth, oral
      hygiene, and fluoride availability. In this article, our aim is to focus on the
      effects of saliva and salivary constituents on cariogenic bacteria and the
      subsequent development of dental caries.

PMID- 11842925
TI  - Natural history and prevention of radiation injury.
AB  - Radiation therapy for cancers of the head and neck can irreversibly damage the
      salivary glands. Xerostomia (subjective oral dryness) develops within the first
      week of therapy and is progressive, with devastating effects on the quality of
      life of the individual. The xerostomia does not correlate with the degree of
      salivary gland hypofunction. The mechanism of tissue injury in humans is still
      unclear, but much progress has been made with animal models. This paper reviews
      the natural history of radiation damage to human salivary glands and highlights
      the inter-individual variations in the responses to and recovery from therapeutic
      radiation. The degree of salivary gland damage is correlated to the dose of
      radiation delivered and the volume of gland included in the field of radiation.
      The molecular mechanism of acute radiation damage is not fully understood;
      however, long-term salivary gland dysfunction is associated with both loss of
      gland weight and loss of acinar cells. Various strategies have been used to
      prevent or alleviate the problem of salivary gland hypofunction following
      therapeutic radiation. This paper reviews the progress made to date and the
      possibilities for future interventions to prevent radiation damage.

PMID- 11842924
TI  - What can transgenic and gene-targeted mouse models teach us about salivary gland
      physiology?
AB  - Thousands of genetically modified mice have been developed since the first
      reports of stable expression of recombinant DNA in this species nearly 20 years
      ago. This mammalian model system has revolutionized the study of whole-animal,
      organ, and cell physiology. Transgenic and gene-targeted mice have been widely
      used to characterize salivary-gland-specific expression and to identify genes
      associated with tumorigenesis. Moreover, several of these mouse lines have proved
      to be useful models of salivary gland disease related to impaired immunology,
      i.e., Sjogren's syndrome, and disease states associated with pathogens. Despite
      the availability of genetically modified mice, few investigators have taken
      advantage of this resource to better their understanding of salivary gland
      function as it relates to the production of saliva. In this article, we describe
      the methods used to generate transgenic and gene-targeted mice and provide an
      overview of the advantages of and potential difficulties with these models.
      Finally, using these mouse models, we discuss the advances made in our
      understanding of the salivary gland secretion process.

PMID- 11842926
TI  - Adrenoceptor-activated nitric oxide synthesis in salivary acinar cells.
AB  - We investigated the cellular regulation of nitric oxide synthase (NOS) activity
      in isolated acinar cells from rat parotid and human labial salivary glands, using
      the newly developed fluorescent nitric oxide (NO) indicator, DAF-2. We found that
      sympathetic stimulation with norepinephrine (NE) caused a strong increase in NO
      synthesis that was not seen after parasympathetic stimulation with acetylcholine.
      In rat parotid acinar cells, we furthermore investigated to which extent the NOS
      activity was dependent on the intracellular free Ca2+ concentration ([Ca2+]i) by
      simultaneously measuring NO synthesis and [Ca2+]i. It was found that a simple
      correlation between the rise in [Ca2+]i and the rate of NO production following
      NE stimulation does not exist, and studies in which [Ca2+]i was elevated by means
      of the Ca2+ ionophore, ionomycin, further established that even a very large rise
      in [Ca2+]i did not cause significant NO synthesis. We furthermore found that
      activating adrenoceptors with NE causes synthesis of cGMP by activating a
      guanylyl cyclase, and that an enhanced [cGMP] evoked by use of caged cGMP causes
      Ca2+ release from internal stores. Thus, upon sympathetic stimulation, salivary
      gland acini synthesize NO that, in addition to playing a role in controlling
      intracellular [Ca2+]i, also might play a role in retrograde signaling processes
      to the surrounding tissue.

PMID- 11842927
TI  - Heterogeneity of high-molecular-weight human salivary mucins.
AB  - The existence of high-molecular-weight glycoproteins in saliva and salivary
      secretions has been recognized for nearly 30 years. These proteins, called
      mucins, are essential for oral health and perform many diverse functions in the
      oral cavity. Mucins have been intensively studied, and much has been learned
      about their biochemical properties and their interactions with oral micro
      organisms and other salivary proteins. In the past several years, the major high
      molecular-weight mucin in salivary secretions has been identified as MUC5B, one
      of a family of 11 human mucin gene products expressed in tissue-specific patterns
      in the gastrointestinal, respiratory, and reproductive tracts. MUC5B is one of
      four gel-forming mucins which exist as multimeric proteins with molecular weights
      greater than 20-40 million daltons. The heavily glycosylated mucin multimers form
      viscous layers which protect underlying epithelial surfaces from microbial,
      mechanical, and chemical assault. Another class of mucin molecules, the membrane
      bound mucins, is structurally and functionally distinct from the gel-forming
      mucins. These proteins do not form multimers and can exist as both secreted and
      membrane-bound forms, with the latter anchored to epithelial cell membranes
      through a short membrane-spanning domain. In the present work, we show that two
      of the membrane-bound mucins, MUC1 and MUC4, are expressed in all major human
      salivary glands as well as in buccal epithelial cells. While the functions of
      these mucins in the oral environment are not understood, it is possible that they
      form a structural framework on the cell surface which not only is cytoprotective,
      but also may serve as a scaffold upon which MUC5B, and possibly other salivary
      proteins, assemble.

PMID- 11842929
TI  - First insights into the molecular basis of pleomorphic adenomas of the salivary
      glands.
AB  - Pleomorphic adenoma, or mixed tumor of the salivary glands, is a benign tumor
      originating from the major and minor salivary glands. Eighty-five percent of
      these tumors are found in the parotid gland, 10% in the minor (sublingual)
      salivary glands, and 5% in the submandibular gland. It is the most common type of
      salivary gland tumor, accounting for almost 50% of all neoplasms in these organs.
      In fact, after the first observation of recurrent loss of chromosome 22 in
      meningioma, this was the second type of benign tumor for which non-random
      chromosomal changes were reported. The rate of malignant change with the
      potential to metastasize has been reported to be only 2 to 3%, and only a few
      cases of metastasizing pleomorphic salivary gland adenomas have been described to
      date. The fact that these tumors arise in organs located in an ontogenetic
      transitional zone, a region where endoderm and ectoderm meet, might be one of the
      reasons for the often-problematic histopathological classification. This type of
      benign tumor has been cytogenetically very well-characterized, with several
      hundreds of tumors karyotyped. In addition to the cytogenetic subgroup with an
      apparently normal diploid stemline (making up approximately 30% of the cases),
      three major cytogenetic subgroups can be distinguished. In addition to a subgroup
      showing non-recurrent clonal abnormalities, another subgroup is various
      translocations involving 12q15. By far the largest cytogenetic subgroup, however,
      consists of tumors with chromosome 8 abnormalities, mainly showing translocations
      involving region 8q12. The most frequently encountered aberration in this group
      is a t(3;8)(p21;q12).

PMID- 11842928
TI  - Salivary cellular signaling and gene regulation.
AB  - Protein tyrosine kinase and protein serine kinase activation has been implicated
      in the regulation of salivary cell proliferation and differentiation. Aberrant
      expression and alterations of certain tyrosine or serine kinases, such as Raf or
      erbB2, are known to trigger salivary tumor development (Li et al., 1997; Cho et
      al., 1999). It has been estimated that there are about 1000 to 2000 protein
      kinases in the mammalian genome, with 100 to 200 of them (i.e., 10%) being
      tyrosine kinase (Hanks and Hunter, 1995). At present, there are approximately 85
      different tyrosine kinases identified in the GenBank database. Based on the
      relatively slow rate of discovery in the past few years, 100 is a better
      approximation of the total number of tyrosine kinases encoded by each mammalian
      genome. It is reasonable to assume that there are about 30 to 50 tyrosine kinases
      expressed in a given cell at a given differentiation/proliferation stage. This
      number is large enough to provide a characteristic tissue-specific tyrosine
      kinase expression profile, but small enough to be identified in a simple
      screening. The hope for tyrosine kinases as differentiation or proliferation
      markers rests with the possibility for the identification and characterization of
      a differentiation/proliferation stage-specific expression pattern in salivary
      cells. Several ligands that transmit signal through receptor tyrosine kinases
      and/or Ras/Raf/ERK kinases have been extensively studied in salivary cells. This
      review focuses mainly on the signaling pathways activated by Raf and Etk.

PMID- 11842930
TI  - Prospects for re-engineering salivary glands.
AB  - In the last decade, two areas of biomedical research--gene therapy and tissue
      engineering--have especially captured the imagination of the public. Both areas
      offer the potential for the treatment of clinical conditions that now are
      considered impossible or extremely difficult to manage by conventional
      therapeutic measures. Gene therapy has made remarkable scientific progress in the
      laboratory, but has yet to realize its enormous clinical promise. Tissue
      engineering studies have led to some tangible clinical breakthroughs, but the
      routine replacement of whole internal organs is still well into the future. This
      report will examine the applications of gene therapy and tissue engineering to
      salivary glands, with a focus on the repair of irreversible gland damage.

PMID- 11842931
TI  - Early genes required for salivary gland fate determination and morphogenesis in
      Drosophila melanogaster.
AB  - Studies of Drosophila salivary gland formation have elucidated the regulatory
      pathway by which the salivary gland fate is determined and the morphogenetic
      processes by which the primordial cells are internalized to form the tubular
      glands. Both the position of the salivary primordia and the number of cells
      recruited to a salivary gland fate are established through a combination of the
      localized expression of the transcription factors SEX COMBS REDUCED (SCR),
      TEASHIRT (TSH) and ABDOMINAL-B (ABD-B), and localized DPP-signaling. Similarly,
      the distinction between the two major cell types, duct and secretory, is
      determined by spatially limited EGF-signaling. Salivary gland formation also
      requires the function of two transcription factors expressed in nearly all cells
      of the developing embryo, EXTRADENTICLE (EXD) and HOMOTHORAX (HTH). Once the
      salivary gland fate is determined, cells of the secretory primordia are
      internalized by an apical constriction mode of invagination. We have
      characterized three genes encoding transcription factors, trachealess (trh),
      huckebein (hkb), and fork head (fkh), that are downstream targets of the salivary
      gland regulators. Mutations in these transcription factors profoundly affect
      salivary gland morphogenesis. trh is required for the formation of the salivary
      duct tubes. hkb determines the order of secretory cell invagination, a regulated
      process critical for determining the final shape of the salivary gland. fkh has
      two early roles in salivary gland formation. fkh both promotes secretory cell
      survival and facilitates secretory cell internalization. trh, hkb, and fkh are
      involved in the formation of not only the salivary duct and secretory tubes, but
      also of other tubular structures, such as the trachea and the gut endoderm. We
      propose that trh, hkb, and fkh may serve as "morphogenetic cassettes" responsible
      for forming tubular structures in a variety of tissues.

PMID- 11842932
TI  - Salivary growth factors in health and disease.
AB  - The salivary gland is considered to be a reservoir of many growth factors in
      rodents. In humans, the epidermal growth factor, basic fibroblast growth factor,
      and insulin and insulin-like growth factor family have also been detected in this
      gland, but their physiological role remains unclear. In this study, we focused on
      bFGF, which is a well-known mitogen for various types of cells, and is present in
      the salivary gland as well as in saliva. The roles of bFGF in the salivary gland
      were investigated by three different procedures. First, the effects of bFGF on
      the salivary gland cells were investigated with a monolayer culture of normal
      submandibular gland cells. The effects of different concentrations of bFGF on the
      second passage of these cultured cells were examined. In both human and rat
      cultured submandibular gland cells, bFGF accelerated the cell proliferation at a
      concentration of 100 ng/mL or higher. Next, an atrophic model of the rat
      submandibular gland was used to examine the ability of bFGF to accelerate tissue
      repair. Two weeks after ductal ligation, the ligature was removed, and various
      amounts of bFGF, isoproterenol, or saline were administered via a retrograde duct
      instillation. Both isoproterenol and bFGF increased acinar and ductal cell
      proliferation significantly. To determine the role of bFGF in saliva, we
      investigated its effect on the healing process of oral mucosal defects. Four
      millimeter mucosal defects were made to the depth of the periosteum in the rat
      palate under anesthesia. bFGF or vehicle alone was applied once only at the time
      of surgery as a suspension. At days 3, 5, and 7 in the bFGF group, significant
      increases in the degree of re-epithelialization were found in treated groups.
      These results indicate that its action as a mitogen stimulus is the major effect
      of bFGF on salivary gland cells and mucosal epithelium.

PMID- 11842934
TI  - Distribution pattern of versican, link protein and hyaluronic acid in the rat
      periodontal ligament during experimental tooth movement.
AB  - The ability of the periodontal ligament (PDL) to rapidly remodel is the basis of
      orthodontic tooth movement. During the tooth movement, matrix proteoglycans (PGs)
      may play important roles in spatial, mechanical and biological aspects for the
      maintenance and repair of the PDL. The aim of this study was to characterize the
      distribution of a large hyaluronic acid (HA)-binding proteoglycan, versican, link
      protein (LP) and HA in the rat molar PDL during experimental tooth movement by
      histochemical and immunohistochemical methods. Experimental tooth movement was
      performed according to Waldo's method. Histologically, regressive changes, such
      as decrease of fibroblasts and collagen fibers and exudative change of edema were
      observed in the compressive side and progressive changes, such as proliferation
      of fibroblasts and collagen fibers, in the strain side one day after treatment.
      By 3 days after tooth movement, regressive or progressive changes were not
      observed in either side. Using monoclonal antibodies specific to versican core
      protein or LP, the positive immunoreactivity for both molecules was constantly
      observed throughout the PDL. After the experimental force was applied to the
      tooth, however, the immunostainings of versican and LP became significantly
      intense only in the compressive side but decreased in the strain side. The
      intensity in the compressive side was strongest one day after the force was
      applied and gradually diminished thereafter. HA of both sides did not change
      during experimental tooth movement. Since HA is present in the PDL, large amounts
      of versican and LP expressed in the compressive side may create large hydrated
      aggregates via their association with HA that dissipates the compressive force
      applied to this tissue.

PMID- 11842933
TI  - Inhibition of alveolar bone loss by matrix metalloproteinase inhibitors in
      experimental periodontal disease.
AB  - Periodontal disease is characterized by excessive host collagenase resulting in
      loss of gingival and periodontal ligament collagen and adjacent alveolar bone.
      Intragingival endotoxin injection induces a model of periodontal disease
      characterized by rapid bone loss with biochemical features similar to that of
      naturally occurring adult periodontitis. CH1766, a peptide with a zinc binding
      moeity which fits into the active site of the enzyme, and CH6631, a hydroxamic
      acid derivative with aryl-substituted sulphonamide residues, are inhibitors of
      matrix metalloproteinases (MMPIs) with differing inhibitory profiles as
      characterized by in vitro assays. In this study, endotoxin was injected into the
      gingivae of rats which were then treated orally with either 3 mg/kg or 30 mg/kg
      of one of the two inhibitory compounds. The gingival tissues were assessed for
      collagenase and gelatinase activity, plus three different pro-inflammatory
      cytokines. In addition, alveolar bone height in defleshed jaws was studied by
      computerized morphometric analysis and scanning electron microscopy. Both drugs
      reduced active and/or total MMP activity, in many cases to normal, and also
      partially normalized cytokine levels as well. A dose-response effect was seen
      with regard to amelioration of lipopolysaccharide-induced alveolar bone loss with
      both drugs. Other than studies with tetracyclines, this is the first report of
      beneficial effects of MMPIs in a model of periodontal disease, strongly
      suggesting that this class of agents could bring therapeutic benefit to patients
      with this disorder, and that periodontal disease can be used as a model to
      demonstrate in vivo efficacy of this class of drugs.

PMID- 11842935
TI  - Expression of fibrillins and tropoelastin by human gingival and periodontal
      ligament fibroblasts in vitro.
AB  - The elastic system fibers consist of three different types, oxytalan, elaunin and
      elastic fibers, which differ in the relative content of microfibrils and elastin.
      In periodontal tissues, oxytalan fibers are known to be distributed in the
      periodontal ligament and gingiva, while elaunin and elastic fibers are present
      only in the gingiva. We examined the in vitro synthesis of microfibrils and
      elastin by human gingival fibroblasts (HGF) and periodontal ligament fibroblasts
      (HPLF). The two kinds of HGF and HPLF were cultured in MEM containing 10% newborn
      calf serum for 30 days. Since fibrillin-1 and fibrillin-2 are the major
      components of microfibrils involved in elastogenesis, we investigated the
      synthesis of fibrillins and tropoelastin in the conditioned medium of HGF and
      HPLF. Western blot analysis revealed fibrillin-1 and fibrillin-2 to occur in the
      HGF and HPLF culture medium, HGF exhibiting a higher level of synthesis than
      HPLF. Tropoelastin, on the other hand, was detected only in the medium of HGF
      after day 24. In addition, analysis of RNA extracted from HGF and HPLF on day 30
      showed that only HGF expressed mRNA encoding tropoelastin. Immunohistochemically,
      accumulation of tropoelastin in the perinuclear area was found only in HGF. These
      results show that HGF expressed microfibrils and elastin, while HPLF expressed
      only microfibrils for the experimental period, and suggest a biochemical basis
      for the different distribution of elastic system fibers of the gingiva and
      periodontal ligament in vivo.

PMID- 11842936
TI  - Binary regulation of interleukin (IL)-6 production by EP1 and EP2/EP4 subtypes of
      PGE2 receptors in IL-1beta-stimulated human gingival fibroblasts.
AB  - Prostaglandin E2 (PGE2) exerts its biological actions via EP receptors, which are
      divided into four subtypes of EP1, EP2, EP3 and EP4. In the present study, we
      investigated whether PGE2 regulated interleukin (IL)-6 production in human
      gingival fibroblasts (HGF) stimulated with IL-1beta and if so, which subtype(s)
      of PGE2 receptors were involved. Indomethacin, a cyclooxygenase inhibitor,
      significantly enhanced IL-1beta-induced IL-6 production by HGF, although it
      completely inhibited IL-1beta-induced PGE2 production. Exogenous PGE2 suppressed
      the IL-1beta-induced IL-6 production. Reverse transcription-polymerase chain
      reaction analysis demonstrated that mRNA of EP1, EP2 and EP4, but not EP3 mRNA,
      was expressed in unstimulated and IL-1beta-stimulated HGF. 11-deoxy-PGE1, a
      selective EP2/EP3/EP4 agonist, and butaprost, a selective EP2 agonist, inhibited
      IL-1beta-induced IL-6 production, although butaprost was less potent than 11
      deoxy-PGE1. 17-phenyl-omega-trinor PGE2, an EP1 agonist, enhanced IL-1beta
      induced IL-6 production. Based on these data, we suggest that PGE2 can up- or
      downregulate IL-1beta-induced IL-6 production via EP1 receptors or via EP2/EP4
      receptors in HGF, respectively. Expression and function of EP1, EP2 and EP4
      receptors in HGF may play critical roles in controlling inflammatory periodontal
      conditions.

PMID- 11842938
TI  - Compositional analysis of root cementum and dentin after Er:YAG laser irradiation
      compared with CO2 lased and intact roots using Fourier transformed infrared
      spectroscopy.
AB  - The present study examines the dental root after Er:YAG laser irradiation,
      compared with CO2 lased and non-treated surfaces, using Fourier Transformed
      Infrared (FTIR) spectroscopy. Freshly extracted human teeth were irradiated by
      Er:YAG laser at an energy output of 40 mJ/pulse, 10 Hz (0.4 watts), with or
      without water coolant, and by CO2 laser at an energy output of 0.5 watts in
      continuous wave mode without coolant. The surfaces were chalky and smooth after
      irradiation by Er:YAG laser with water coolant, were charred and irregular after
      irradiation by Er:YAG laser without water coolant, and were completely carbonized
      after CO2 laser irradiation. The FTIR profiles from samples of the surfaces that
      were irradiated by Er:YAG laser with water coolant were similar to those from non
      treated samples, except for a slight decrease on the OH and amide bands, which
      are mainly related to organic components. This decrease was observed to be
      extreme after CO2 laser irradiation and moderate after Er:YAG laser irradiation
      without coolant. The formation of new bands showing toxic substances was observed
      to a large extent after CO2 laser irradiation and to a smaller extent after
      Er:YAG laser irradiation without water coolant. In contrast, no such bands were
      detected after Er:YAG laser irradiation with water coolant. The present results
      show that these laser treatments selectively ablated more organic components than
      inorganic components and that Er:YAG laser irradiation with water coolant did not
      cause major compositional changes or chemically deleterious changes in either
      root cementum or dentin.

PMID- 11842939
TI  - Plasminogen activating capacity in gingival fluid from deteriorating and stable
      periodontal pockets.
AB  - The plasminogen activating system plays an important role in tissue proteolysis
      in physiological as well as pathological processes. Earlier studies have shown
      high concentrations of the plasminogen activator t-PA as well as its inhibitor
      PAI-2 in gingival crevicular fluid (GCF). In addition, gingival inflammatory
      reactions have been related to increases in t-PA and PAI-2. In order to explore
      the potential role of the plasminogen activating system for the development of
      destructive periodontal disease, the aim of this study was to assess the balance
      of the activator t-PA to the inhibitor PAI-2 in GCF from patients, clinically
      defined to represent different periodontal conditions. The Progression Group
      consisted of 12 periodontitis patients with 1 or more sites having shown an
      increased pocket depth of > or = 3 mm during the last 2 years of maintenance care
      and with > or = 8 unchanged or improving sites during the period. The Non
      Progression Group consisted of patients who had shown a decreased or unchanged
      pocket depth of all sites during the last 3 years of maintenance care. Sampling
      of GCF was done with small disks of Millipore-filter, and t-PA and PAI-2 were
      analyzed with ELISAs. There was no difference in the t-PA/PAI-2 ratio between the
      two groups. However, an intra-individual comparison within the Progression Group
      showed a higher ratio at the deteriorating sites than at the stable sites. Even
      though no difference was found between the groups, the higher t-PA/PAI-2 ratio at
      the deteriorating sites in the Progression Group suggests an involvement of the
      plasminogen activating system in the proteolytic events leading to breakdown of
      the tooth supporting tissues.

PMID- 11842937
TI  - Effects of interleukin-4 on proteoglycan accumulation in human gingival
      fibroblasts.
AB  - In inflammatory gingival diseases, cytokines have been demonstrated to play
      critical roles by coordinating the stimulation of immunological and connective
      tissue cells. The activities of these cells, degrading and remodeling
      extracellular matrices, constitute the major pathological and repair processes.
      Thus, elucidating cellular and molecular events occurring in inflamed connective
      tissues is crucial for the understanding and treatment of inflammation. In order
      to test a hypothesis that proinflammatory cytokines affect metabolism of major
      extracellular matrix molecules, we studied metabolism of proteoglycans (PGs) by
      human gingival fibroblasts (HGF) under the influence of interleukin-4 (IL-4) as a
      model of gingivitis. HGF in cell culture were metabolically radiolabeled using
      [3H]glucosamine and [35S]sulfate in the presence or absence of IL-4, and the
      labeled PGs were analyzed by chromatographic techniques. The incorporation of 35S
      into PGs increased with IL-4 both in media and cell layer. At 100 ng/ml of IL-4,
      the increment of 35S incorporation over control culture was 16-39% (p<0.001) in
      media and 12-35% (p=0.01) in cell layer. The 35S-labeled macromolecules were PGs
      containing heparan sulfate (HS) and chondroitin sulfate (CS) chains. From the
      molecular weight and glycosaminoglycan composition analyses, versican and
      perlecan-type and biglycan and decorin-type were very likely to be the major PG
      constituents both in media and cell layer. IL-4 stimulated synthesis of versican
      and perlecan-type more potently than biglycan and decorin-type. With IL-4
      treatment, the ratio of CSPG/HSPG decreased in media and increased in cell layer.
      This ratio suggested that syndecan family HSPGs were also present in HGF. In
      conclusion, IL-4 stimulated accumulation of CS/HSPGs in human gingival
      fibroblasts.

PMID- 11842941
TI  - Dialister pneumosintes, a new putative periodontal pathogen.
AB  - Recent studies have implicated Dialister pneumosintes as a candidate periodontal
      pathogen. This study determined the association of subgingival D. pneumosintes
      with demographic variables (age and gender) and the presence of subgingival
      periodontopathic Bacteroides forsythus and Porphyromonas gingivalis. Microbial
      identification by established PCR techniques was performed in samples from 149
      periodontitis patients. Subgingival D. pneumosintes occurred with significantly
      higher prevalence in older individuals and was closely associated with
      subgingival B. forsythus. D. pneumosintes may play an important role in the
      microbial complex responsible for destructive periodontal disease.

PMID- 11842940
TI  - Keratinocyte growth factor (KGF)-1 and -2 protein and gene expression in human
      gingival fibroblasts.
AB  - The onset and progression of periodontal disease is associated with significant
      changes in the epithelial component of the attachment complex. From the early to
      the advanced stages of periodontal disease increased epithelial cell
      proliferation, migration and invasion into the surrounding connective tissue
      takes place. Concomitantly there is a significant increase in proinflammatory
      cytokine expression in periodontal tissue and quantitative and qualitative
      changes in the subgingival microflora, including an increase in gram-negative
      microorganisms. One of the most significant virulence factors of these bacteria
      is lipopolysaccharide (LPS) connected to the outer membrane. Two important growth
      factors controlling epithelial behavior are Keratinocyte Growth Factor-1 (KGF-1)
      and -2 (KGF-2). Connective tissue cells express these growth factors, but only
      epithelial cells respond to them. We studied the effect of proinflammatory
      cytokines and LPS on gingival fibroblast expression of KGF-1 and KGF-2 in vitro.
      Gingival fibroblasts were found to express KGF-1 and -2 in culture but only KGF-1
      protein and gene expression was stimulated by serum, in a concentration-dependent
      manner by proinflammatory cytokines IL-1alpha, IL-1beta, TNF-alpha and IL-6 and
      LPS isolated from Porphyromonas gingivalis and Escherichia coli. The local
      increase in proinflammatory cytokine expression and the accumulation of LPS in
      disease sites may therefore stimulate gingival fibroblast expression of KGF-1. We
      hypothesize that this local increase in KGF-1 expression may, via a paracrine
      mechanism, stimulate local epithelial cell proliferation, migration and invasion
      during the onset and progression of periodontitis.

PMID- 11842943
TI  - The role of nutrition in human acid-base homeostasis.

PMID- 11842942
TI  - Hepatocyte growth factor (HGF) in periodontal disease: detection of HGF in
      gingival crevicular fluid.
AB  - Hepatocyte growth factor (HGF) acts as a mitogen, motogen, morphogen, anti
      apoptotic factor, and scatter factor for various kinds of epithelial cells. It is
      a protein secreted by mesenchymal cells such as fibroblasts, and promotes
      motility and matrix invasion of epithelial cells. To clarify whether HGF is
      involved in periodontal disease, this study was conducted to determine whether
      HGF is present in gingival crevicular fluid (GCF) and to investigate the
      relationship between levels of HGF and the clinical parameters of periodontal
      disease, probing depth (PD), gingival index (GI) and bleeding on probing (BOP).
      We examined and collected GCF samples from 80 sites in 38 subjects with
      periodontal or other oral diseases. The concentrations of HGF, IL-1beta and PGE2
      were determined by ELISA, and active collagenase activity was determined by
      functional assay. The HGF level correlated positively with PD and GI, and was
      significantly higher in specimens from BOP-positive sites and those where PD
      exceeded 4 mm compared with those from sites that were BOP-negative or with a PD
      less than 3 mm. There was a significant positive correlation between the
      concentrations of HGF and IL-1beta. These results indicate that the HGF level in
      GCF correlates well with clinical parameters of periodontal disease, and suggest
      that HGF may be involved in epithelial invasion through its role as a scatter
      factor.

PMID- 11842944
TI  - History of nutrition and acid-base physiology.
AB  - In the 17th century the notion of nutrition and diet changed in northern European
      countries. First chemical experiments fostered the idea that salts resulted from
      a union of acids and bases. Digestion was no more regarded as a process of
      cooking but a succession of fermentations controlled by a balanced production of
      acids and alkali. Life seemed to depend on the equilibrium of acids and alkalis.
      In the 19th century food was systematically analysed for the content of energy
      and macronutrients and first scientifically based nutritional standards were
      formulated. The preferred use of processed food from the new food industry
      resulted in epidemics of nutritional disorders. Acidosis seemed to be a plausible
      pathogenic factor. Practitioners (S Ishizuka, H Hay, FX Mayr) formulated holistic
      doctrines integrating the concept of balance of acids and bases and recommending
      food with an excess of alkali. New micromethods to determine the concentration of
      electrolytes and blood acid-base status promoted physiological and clinical
      research into acid-base metabolism in the 1960s. In the new physiologically based
      terminology of systemic acid-base status, the relationship between blood acid
      base status and net acid intake or excretion was, however, incorrectly
      simplified. In the 1970s metabolic acidosis was observed in patients on
      chemically defined diets and parenteral nutrition. Based on the data of
      comprehensive acid-base balance studies, calculation models were used to estimate
      renal net acid excretion from nutrient intake and to predict the potential renal
      acid load of single foods. Extrapolating current trends to the future, one can
      say that acid-base physiology will probably remain a challenge in nutrition and
      functional medicine over the next few years. The challenge will include new
      concepts for the manipulation of nutritional acid load in sports, dietetics and
      preventive medicine as well as new definitions of the upper intake level of
      potential renal acid load in functional foods and the monitoring of renal net
      acid excretion in populations.

PMID- 11842946
TI  - Influence of nutrition on acid-base balance--metabolic aspects.
AB  - BACKGROUND: Nutrition has long been known to strongly influence acid-base
      balance. Recently, we have shown that it is possible to appropriately estimate
      the renal net acid excretion (NAE) of healthy subjects from the composition of
      their diets. AIM OF THE STUDY: 1) To briefly present a physiologically based
      calculation model that allows a reasonable estimation of the analytically
      determined urinary NAE, 2) to summarize the underlying metabolic mechanisms and
      3) to study the specific effect of protein on ammoniagenesis which may
      counteract, to a small degree, the primary acid load-increasing potential of
      protein. METHODS: The calculation model and the algorithm for predicting the
      dietary acid load are summarized, major metabolic (and intestinal) pathways of
      acid and base equivalents are explained, and urinary excretion rates of ammonium
      and NAE were specifically examined with special regard to the respective protein
      intake levels. For the latter examinations, data from diet experiments in adults
      and epidemiological data from children (protein intake; NAE, pH, and ammonium
      excretion in 24-h urine samples) were analyzed. RESULTS: The paper shows that the
      diet-induced generation of acidity and alkalinity is not only determined by the
      metabolism (oxidation) of sulfur-containing amino acids and organic acid anions
      of alkali salts, respectively. The intestine is also directly involved in the
      generation of food-derived acid or alkali loads which is due to the considerably
      different intestinal absorption rates of relevant food components, i. e., protein
      and minerals. Further analyses of the interrelation between diet and acid-base
      status revealed that increasing protein intake (despite its potential to increase
      NAE) also significantly improves the capacity for renal net acid excretion by
      stimulating urinary ammonium excretion. CONCLUSION: An adequate concept to
      estimate renal NAE and potential renal acid loads from dietary intakes must
      consider the specific bioavailability of the individual nutrients. Furthermore,
      an increased protein intake does not necessarily result in an accordingly
      increased use of endogenous acid excretion capacity for two reasons: 1)
      additional alkali loads in an appropriately composed diet can compensate for the
      protein-related raised acid production and 2) protein itself moderately improves
      the renal capacity to excrete net acid by increasing the endogenous supply of
      ammonia which is the major urinary hydrogen ion acceptor.

PMID- 11842945
TI  - Diet, evolution and aging--the pathophysiologic effects of the post-agricultural
      inversion of the potassium-to-sodium and base-to-chloride ratios in the human
      diet.
AB  - Theoretically, we humans should be better adapted physiologically to the diet our
      ancestors were exposed to during millions of years of hominid evolution than to
      the diet we have been eating since the agricultural revolution a mere 10,000
      years ago, and since industrialization only 200 years ago. Among the many health
      problems resulting from this mismatch between our genetically determined
      nutritional requirements and our current diet, some might be a consequence in
      part of the deficiency of potassium alkali salts (K-base), which are amply
      present in the plant foods that our ancestors ate in abundance, and the exchange
      of those salts for sodium chloride (NaCl), which has been incorporated copiously
      into the contemporary diet, which at the same time is meager in K-base-rich plant
      foods. Deficiency of K-base in the diet increases the net systemic acid load
      imposed by the diet. We know that clinically-recognized chronic metabolic
      acidosis has deleterious effects on the body, including growth retardation in
      children, decreased muscle and bone mass in adults, and kidney stone formation,
      and that correction of acidosis can ameliorate those conditions. Is it possible
      that a lifetime of eating diets that deliver evolutionarily superphysiologic
      loads of acid to the body contribute to the decrease in bone and muscle mass, and
      growth hormone secretion, which occur normally with age? That is, are
      contemporary humans suffering from the consequences of chronic, diet-induced low
      grade systemic metabolic acidosis? Our group has shown that contemporary net acid
      producing diets do indeed characteristically produce a low-grade systemic
      metabolic acidosis in otherwise healthy adult subjects, and that the degree of
      acidosis increases with age, in relation to the normally occurring age-related
      decline in renal functional capacity. We also found that neutralization of the
      diet net acid load with dietary supplements of potassium bicarbonate (KHCO3)
      improved calcium and phosphorus balances, reduced bone resorption rates, improved
      nitrogen balance, and mitigated the normally occurring age-related decline in
      growth hormone secretion--all without restricting dietary NaCl. Moreover, we
      found that co-administration of an alkalinizing salt of potassium (potassium
      citrate) with NaCl prevented NaCl from increasing urinary calcium excretion and
      bone resorption, as occurred with NaCl administration alone. Earlier studies
      estimated dietary acid load from the amount of animal protein in the diet,
      inasmuch as protein metabolism yields sulfuric acid as an end-product. In cross
      cultural epidemiologic studies, Abelow found that hip fracture incidence in older
      women correlated with animal protein intake, and they suggested a causal relation
      to the acid load from protein. Those studies did not consider the effect of
      potential sources of base in the diet. We considered that estimating the net acid
      load of the diet (i. e., acid minus base) would require considering also the
      intake of plant foods, many of which are rich sources of K-base, or more
      precisely base precursors, substances like organic anions that the body
      metabolizes to bicarbonate. In following up the findings of Abelow et al., we
      found that plant food intake tended to be protective against hip fracture, and
      that hip fracture incidence among countries correlated inversely with the ratio
      of plant-to-animal food intake. These findings were confirmed in a more
      homogeneous population of white elderly women residents of the U.S. These
      findings support affirmative answers to the questions we asked above. Can we
      provide dietary guidelines for controlling dietary net acid loads to minimize or
      eliminate diet-induced and age-amplified chronic low-grade metabolic acidosis and
      its pathophysiological sequelae. We discuss the use of algorithms to predict the
      diet net acid and provide nutritionists and clinicians with relatively simple and
      reliable methods for determining and controlling the net acid load of the diet. A
      more difficult question is what level of acidosis is acceptable. We argue that
      any level of acidosis may be unacceptable from an evolutionarily perspective, and
      indeed, that a low-grade metabolic alkalosis may be the optimal acid-base state
      for humans.

PMID- 11842947
TI  - Nutrition, acid-base status and growth in early childhood.
AB  - Optimal growth is only possible in a well-balanced "inner milieu". Premature
      infants are especially vulnerable for disturbances of acid-base metabolism with a
      predisposition to metabolic acidosis due to a transient disproportion between age
      related low renal capacity for net acid excretion (NAE) and an unphysiologically
      high actual renal NAE on nutrition with standard formulas. During a 50 month
      period, 452 low birth-weight infants were screened for spontaneous development of
      incipient late metabolic acidosis (ILMA), an early stage during the development
      of retention acidosis, characterized by maximum renal acid stimulation (MRAS,
      urine-pH < 5.4) on two consecutive days but still compensated systemic acid-base
      status. Compared with controls, patients with ILMA showed higher serum creatinine
      values, an increased urinary excretion of sodium, aldosterone and nitrogen, but
      only slightly lower blood pH (7.38 vs 7.41) and base excess (-2.8 vs. 0.2 mmol/l)
      with respiratory compensation (PCO2 35 vs 37 mm Hg). Patients with altogether 149
      episodes of ILMA were subsequently randomly allocated to either treatment with
      NaHCO3 2 mmol/kg/d for 7 days or no special therapy in protocol I, or NaHCO3 vs
      NaCl each 2 mmol/kg/d for 7 days in protocol II. Patients of protocol I with
      persistent MRAS for 7 days showed lowest weight gain and a tendency for a further
      increase in urinary aldosterone and nitrogen excretion. NaCl supplementation
      (protocol II) seemed to promote weight gain without affecting either impaired
      mineralization or suboptimal nitrogen retention. Patients with alkali therapy
      under both protocols showed normal weight gain and normalization of hormonal
      stimulation, mineralization (protocol II) and nitrogen assimilation. Modification
      of the mineral content of a standard preterm formula decreased renal NAE to the
      low level seen on alimentation with human milk and reduced the incidence of ILMA
      in preterm and small-for-gestational-age infants to 1%. The data show that ILMA
      is associated with impaired growth. Activation of secondary homeostatic
      mechanisms (extracellular volume contraction, depletion of disposable net base
      pools) might be important for impaired growth. Production of new formulas for
      reduced renal NAE could be an effective general preventive measure to reduce the
      clinical importance of one component of mixed acid-base disorders in early
      childhood.

PMID- 11842948
TI  - The acid-base hypothesis: diet and bone in the Framingham Osteoporosis Study.
AB  - BACKGROUND: There continues to be considerable debate about the role of acid vs.
      basic components of the diet on the long-term status of bone mineral density.
      AIM: In a set of two analyses, we examined the effect of components in the diet
      thought to have basic effects (magnesium, potassium, fruit, vegetables) and acid
      effects (protein) on bone mineral density in an elderly cohort. METHODS: Bone
      mineral density of participants in the Framingham Osteoporosis Study was measured
      at three hip sites and one forearm site at two points in time, four years apart.
      At the time of baseline measurement, participants ranged in age from 69-97 years.
      Dietary intake was assessed at baseline by food frequency questionnaire. RESULTS:
      As hypothesized, magnesium, potassium, fruit and vegetable intakes were
      significantly associated with bone mineral density at baseline and among men,
      with lower bone loss over four years. In contrast to the hypothesis, higher
      rather than lower protein intakes were associated with lower bone loss.
      CONCLUSION: Together these results support the role of base forming foods and
      nutrients in bone maintenance. The role of protein appears to be complex and is
      probably dependent on the presence of other nutrients available in a mixed diet.
      A balanced diet with ample fruit and vegetables and adequate protein appears to
      be important to bone mineral density.

PMID- 11842950
TI  - Animal nutrition and acid-base balance.
AB  - In domestic animals, acid-base balance may be influenced by nutrition. The major
      research effort in this area has been made on the prevention of hypocalcemic
      postparturient paresis in dairy cows. This disorder is caused by the sudden
      increase of calcium secretion into the colostrum. The manipulation of the dietary
      cation-anion difference makes it possible to maintain the cows in metabolic
      acidosis during the critical period that precedes calving, presumably via a
      mechanism that involves the strong ion difference in the extracellular fluid. As
      a consequence the mobilization of calcium is enhanced and the incidence of the
      disorder is decreased. Conversely, a dietary induced metabolic alkalosis leads to
      a more severe degree of hypocalcemia and the incidence of the disease is
      increased. The underlying mechanisms of the prevention are only partially
      understood. Nevertheless, this preventive method is already widely applied in
      practice. Nutrition effects on acid-base balance also influence growth and food
      intake in higher vertebrates and fish. As a consequence, the incidence of
      developmental orthopedic diseases in fast-growing domestic animal species may be
      affected. Also, the bone mineral content of athletic horses may be influenced by
      dietary induced modification of the acid-base status. The mineral loss due to
      metabolic acidosis may lead to an increase in the incidence of stress fractures.
      This overview should give insight into relevant aspects of nutrition and acid
      base balance in domestic animal species.

PMID- 11842949
TI  - Acid-base imbalance and the skeleton.
AB  - Humans generally consume a diet that generates metabolic acids leading to a
      reduction in the concentration of systemic bicarbonate and a fall in pH. In vitro
      experiments indicate that this metabolic acidosis causes a release of calcium
      from bone that initially is simply due to physicochemical dissolution of the
      mineral. On a more chronic basis metabolic acidosis alters bone cell function;
      there is an increase in osteoclastic bone resorption and a decrease in
      osteoblastic bone formation. Concomitant with the dissolution and resorption of
      the bone mineral there is buffering of the addition protons by bone leading to
      restoration of the systemic pH. Interestingly respiratory acidosis, caused by an
      increase in the partial pressure of carbon dioxide induces far less bone
      dissolution and resorption and the additional hydrogen ions are not buffered by
      bone. As we age we are less able to excrete these metabolic acids due to the
      normal decline in renal function. We hypothesize that a slight, but significant,
      metabolic acidosis leads to greater loss of bone mineral and increase potential
      to fracture.

PMID- 11842951
TI  - Minimal-invasive approach to study pulmonary, metabolic and renal responses to
      alimentary acid-base changes in conscious rabbits.
AB  - BACKGROUND: Systemic acid-base balance is maintained by the complex interplay of
      renal and pulmonary control functions and metabolic adaptations, whereby intake
      and mineral composition of feed are important factors. AIM OF THE STUDY: It was
      intended to explore the role of alimentary acid-base load and carbonic anhydrase
      activity for regulatory responses of renal, pulmonary or metabolic origin in
      rabbits as typical herbivores. METHODS: Sixty-eight conscious male rabbits (about
      3.5 kg) were kept in a metabolic cage, to determine daily water intake, urine
      excretion and food consumption. Different groups were fed either alkali-rich
      rabbit standard pellets, or modified rabbit chow with low Ca++-content, or a
      special diet with very low alkali content, or standard food together with a low
      oral dose (about 20 mg x kg(-1) x d(-1)) acetazolamide. Samples from the central
      ear artery were analyzed for blood gases (PaO2, PaCO2), pHa, base excess (BE) and
      actual bicarbonate (HCO3a-). The metabolic CO2 production (VCO2 STPD) was
      determined, to calculate alveolar ventilation (VA BTPS). Anaerobically collected
      urine was analyzed for pHu and for concentrations of bicarbonate/carbonate (HCO3
      /CO3--), ammonium (NH4+), and phosphate. RESULTS: 1) Systemic BE was not affected
      by alimentary alkali load, either varied spontaneously by standard food intake or
      by the low-Ca++ diet, and decreased only slightly on the low-alkali diet, but
      distinctly upon carbonic anhydrase inhibition. 2) Under all conditions of
      alimentation, PaCO2 was closely correlated with BE without a detectable set
      point, the normal-range variability of BE being sufficient to elicit
      corresponding changes in VA. In contrast, acetazolamide led to much lower values
      of PaCO2 than predicted by the reference PCO2/BE relationship, being primarily
      caused by significant reductions in VCO2 (> 20%). 3) Prior to other systems,
      renal base excretion, normally being high on species-adapted standard chow,
      closely followed any variation of alimentary alkali load and approached zero upon
      the low-alkali diet. It was, however, not significantly influenced by carbonic
      anhydrase (CA) inhibition on alkalirich alimentation. CONCLUSIONS: Blood acid
      base balance in rabbits is maintained over a wide range of alimentary alkali load
      by effective adaptation of renal base excretion, independent of CA activity.
      Ventilatory pH control is perpetuated even in the normal range of BE, provided
      metabolic rate is not impaired, e. g., by CA inhibition. These results may help
      one understand the different manifestations of acid-base disorders in body fluids
      under clinical conditions.

PMID- 11842952
TI  - Necrotizing fasciitis: a fourteen-year retrospective study of 163 consecutive
      patients.
AB  - This review was prompted by continued public and professional interest of
      necrotizing fasciitis as well as worldwide increases in the incidence of
      streptococcal invasive infections. Our objective was to outline the clinical
      course of necrotizing fasciitis and delineate factors relating to mortality among
      163 diagnosed patients. Over 14 years patients diagnosed with necrotizing
      fasciitis were reviewed for patient history, comorbid conditions, and progression
      of clinical course. A logistic regression model was used to identify factors
      increasing mortality risk among necrotizing fasciitis patients. Nearly 17 per
      cent of the patients showed no identifiable antecedent trauma. Seventy-one per
      cent of tissue culture-positive patients (145) had multibacterial infections.
      Although no streptococcal species were recovered from one-third of these culture
      positive patients there was an increase in mortality noted with beta
      Streptococcus infections. Ninety-six per cent of the patient deaths were
      correlated with variables organized into the following categories: 1) patient
      history (intravenous drug use and age <1 or >60 years), 2) comorbid conditions
      (cancer, renal disease, and congestive heart failure), 3) characteristics of
      clinical course (trunk involvement, positive blood cultures, peripheral vascular
      disease, and positive cultures for beta-streptococcus or anaerobic bacteria), and
      4) quantitative timeline of clinical course (time: injury to diagnosis, diagnosis
      to treatment). Mortality is correlated to patient history, comorbid conditions,
      and progression of clinical course. Necrotizing fasciitis can occur
      idiopathically and is generally a polymicrobial infection that sometimes occurs
      in the absence of streptococci. Clearly the mortality and morbidity associated
      with necrotizing fasciitis can be decreased with clinical awareness, early
      diagnosis, adequate surgical debridement, and intensive supportive care.

PMID- 11842953
TI  - Percutaneous endoscopic gastrostomy complications in a tertiary-care center.
AB  - Since its introduction in 1980 the percutaneous endoscopic gastrostomy (PEG) has
      become the procedure of choice for establishing enteral access. However, there is
      still a relatively high complication rate associated with PEG placement. We
      reviewed the complications associated with PEG placement at our tertiary-care
      referral center. A retrospective chart review was conducted on patients over 17
      years of age undergoing PEG placement between January 1, 1994 and March 1, 1996.
      Indications for surgery, antibiotic use, and postoperative complications were
      determined. There were 166 PEGs placed during this time and 27 (16.3%)
      complications. There was one death (0.6%) directly related to PEG placement.
      Thirteen patients (7.8%) died within 30 days of PEG placement and an additional
      12 patients (7.2%) died before leaving the hospital. Wound infections occurred in
      nine (5.4%) patients including one case of necrotizing fasciitis. Only four of
      153 (2.6%) patients who received preoperative antibiotics developed wound
      infections, whereas five of 13 (38.5%) patients without antibiotic prophylaxis
      developed infections. We conclude that percutaneous endoscopic gastrostomy is a
      safe and effective way of establishing enteral access in most patients. A
      relatively high mortality rate can be expected as a result of underlying medical
      problems. Antibiotics should be given to help prevent local wound infections.

PMID- 11842954
TI  - Primary malignant large bowel lymphoma.
AB  - Primary gastrointestinal (GI) lymphomas constitute about 5.6 per cent of total
      gut neoplasms. The involvement of large bowel as primary site is all the more
      rare. We carried out this study to evaluate the prevalence and
      clinicopathological features of large bowel lymphoma at Gujarat Cancer and
      Research Institute and to compare our findings with published literature. We
      carried out a retrospective analysis of the records of histologically diagnosed
      cases of large bowel lymphoma over a 5 year period. A total of eight cases of
      large bowel lymphoma were identified compared with 57 cases of primary GI
      lymphoma of other sites, constituting about 12.3 per cent (eight of 65) of all GI
      lymphomas. Peak incidence was observed in the second decade of life with a mean
      age at presentation of 30.6 years (range 4-70 years). A male-to-female ratio of
      one to two was observed. The most commonly presenting feature was altered bowel
      habits and diarrhea in more than 50 per cent of the patients. One patient
      presented with acute intestinal obstruction. Diagnosis was made by colonoscopic
      biopsies in all but one case. All of the patients were treated with surgery and
      adjuvant chemotherapy. A 4-year disease-free survival of 66.7 per cent was
      observed (95% confidence interval 0.05-1.28). There was no significant difference
      in survival in patients with high-grade versus low-grade tumors (50% vs 66.7%; P
      = 0.88) and stage of disease (75% vs 50%; P = 0.45) in stage II and III
      respectively. We conclude that large bowel lymphoma is a curable disease if
      treated aggressively. We suggest that all patients should be treated by primary
      surgery and should receive adjuvant chemotherapy.

PMID- 11842955
TI  - Compartment syndrome in multiple uninjured extremities: a case report.
AB  - Compartment syndrome is a common problem in trauma patients. It can occur within
      any space bound by a dense fascial layer, such as the extremities or abdomen. It
      exists when increased tissue pressure within the limited anatomic space
      compromises perfusion. Failure to decompress the compartment leads to a self
      perpetuating ischemia-edema process and resultant irreversible tissue damage. In
      the extremities, it typically arises from a vascular injury in that same
      extremity. Herein is reported a case of the unexpected development of compartment
      syndrome in multiple uninjured extremities in a trauma patient with hypotension
      requiring systemic vasopressors.

PMID- 11842956
TI  - Transduodenal extended sphincteroplasty and removal of ventral duct pancreatic
      calculi.
AB  - The surgical treatment of chronic pancreatitis and associated ductal calculi
      typically involves drainage of the main pancreatic duct or parenchymal resection.
      Treatment of isolated symptomatic pancreatic duct calculi is usually approached
      by endoscopic techniques. Herein is described a case report of operative
      transduodenal extraction of symptomatic pancreatic calculi of the ventral
      pancreas in a patient with a prior distal pancreatectomy. This case represents an
      uncommon yet valuable option in selected patients in whom endoscopic treatments
      have failed or are unavailable.

PMID- 11842957
TI  - Epithelial (epidermoid) splenic cysts in childhood: surgical management of eight
      cases.
AB  - We report eight cases of splenic epithelial cysts in childhood to summarize our
      clinical experience and to discuss surgical management. Six boys and two girls,
      aged 8 to 14 years (mean 10.8 years) were diagnosed over a 16-year period. No
      patients had a history of preceding trauma or related infection. Presenting
      symptoms were dull (two) or acute (one) left hypochondrium pain and diffuse
      abdominal pain (one). In four children the cyst was an incidental finding.
      Ultrasound and/or CT revealed cysts of diameter 2.9 to 14 cm and radionuclide
      scan showed a reduced uptake in the splenic area of concern. At operation
      variable amounts--up to 1500 mL--of liquid were aspirated from the cysts. Splenic
      artery ligation was undertaken in six cases adjunctively to cystectomy. One total
      splenectomy was performed because the splenic parenchyma was totally replaced by
      the cyst. Recurrence occurred in one case, in which multiple tiny communicating
      cysts were detected. Histology revealed epithelial (n = 5) or stratified squamous
      (n = 3) lining. Five patients were seen again 0.5 to 5 years later and they were
      asymptomatic and with a normal ultrasound, CT, or radionuclide scan. Cyst
      excision was an effective treatment. Adjunctive splenic artery ligation when
      performed controlled hemorrhage. Other surgical methods to manage splenic cysts
      are discussed.

PMID- 11842958
TI  - Daedalus revisited: a call for redesign of the bougie esophageal dilator.
AB  - We report a case of a patient undergoing gastric bypass in which an improperly
      introduced bougie dilator resulted in esophageal perforation and we examine the
      matter using a human-factors approach. The Institute of Medicine's widely
      distributed 1999 report estimated that up to 98,000 Americans die each year as a
      result of preventable errors with the operating room being a particularly error
      prone environment. The report suggests that the majority of errors are not the
      result of poor provider performance but instead are the result of inherent
      systems-based problems. Perforation can be associated with significant negative
      outcome; modifying factors include experience, appreciating anatomical details,
      and cognizance of mechanisms of perforation. Human-factors research reveals that
      1) humans are prone to err and 2) the majority of errors are not the result of
      personal inadequacy but instead are the product of defects in the design of
      health care environmental systems in which that work occurs. Here during a highly
      complex surgical procedure a simple preventable human error occurred, one often
      associated with significant negative outcome. We suggest a simple solution in
      line with a human-factors approach that might prevent future occurrences.

PMID- 11842959
TI  - Renal artery pseudoaneurysm and arteriovenous fistula to the inferior vena cava:
      a late complication following laparoscopic cholecystectomy.
AB  - Major vascular injuries during laparoscopic procedures are rare but potentially
      life-threatening if not promptly diagnosed and treated. We report a case in which
      the placement of a trocar during a laparoscopic cholecystectomy caused damage to
      the right renal artery and led to the development of a pseudoaneurysm. The
      pseudoaneurysm of the right renal artery then eroded into the inferior vena cava
      resulting in an arteriovenous fistula that eventually caused right renal failure,
      systolic and diastolic hypertension, and congestive heart failure. The
      recognition of this complication was delayed and the patient was referred for
      surgery 5 years after the laparoscopic procedure. He then successfully underwent
      right nephrectomy, resection of the pseudoaneurysm, and closure of the fistula.

PMID- 11842960
TI  - The economic benefit of practice guidelines for stress ulcer prophylaxis.
AB  - The development of practice guidelines is an effective way to provide consistent
      and cost-effective patient care. Despite much progress in developing practice
      guidelines for various other clinical problems data documenting the efficacy of
      these guidelines are lacking. The purpose of this study was to compare usage
      patterns and cost effectiveness of a stress ulcer prophylaxis guideline in a
      trauma intensive care unit. The trauma intensive care unit team was observed for
      a 50-day period. Immediately after this period a stress ulcer prophylaxis
      guideline was implemented, and the team was again observed for a 50-day period.
      All information was recorded prospectively. The trauma intensive care unit team
      was blind to the existence of the study. The days of appropriate use of
      prophylaxis (ulcer prophylaxis prescribed per the practice guidelines) and
      inappropriate use (use other than per the practice guidelines) in each study
      phase and the resulting costs were calculated as the primary measurement of
      outcome. Forty-six patients were studied. The use of practice guidelines in the
      period after the guideline was implemented of the study reduced overall stress
      ulcer prophylaxis by 17 per cent (P = 0.04). The appropriate prophylaxis was not
      significantly different when comparing the two periods of study; however,
      inappropriate use of prophylaxis (and associated charges) was statistically
      significantly less frequent after implementation of the practice guidelines. No
      patients developed clinically important gastrointestinal bleeding. The estimated
      annual savings of $102,895 in patient charges and $11,333 in actual drug costs in
      our trauma intensive care unit were due to the implementation of stress ulcer
      prophylaxis guidelines. We conclude that use of practice guidelines can
      significantly reduce patient charges without compromising patient care.

PMID- 11842961
TI  - Hand-assisted laparoscopic radical nephrectomy: comparison with transabdominal
      radical nephrectomy.
AB  - The purpose of this study was to investigate whether hand-assisted laparoscopic
      radical nephrectomy (HALN) has benefits over the traditional transabdominal
      radical nephrectomy. More specifically we focused on the use of the hand-assisted
      technique as a definitive oncologic procedure for renal cancers. This study is a
      retrospective nonrandomized study comparing 12 hand-assisted laparoscopic radical
      nephrectomies with 12 transabdominal radical nephrectomies. All patients included
      in the study had the preoperative diagnosis of renal mass. HALN population
      averaged 1.83 +/- 1.64 (mean +/- standard deviation) major comorbidities versus
      1.08 +/- 0.8 open (P = 0.032). The HALN OR time averaged 103 +/- 32.8 versus 57
      +/- 18.3 minutes open (P = 0.001). The estimated blood loss mean for HALN was 83
      versus 318 cm3 open (P = 0.001). Length of stay for HALN was 4.9 +/- 2.2 versus
      5.9 +/- 2.9 days (P = 0.35). Days to regular diet was 2.9 +/- 2.3 in HALN versus
      3.5 +/- 2.11 open (P = 0.52). Days of intravenous pain medications were 1.8 +/-
      0.72 HALN versus 3.0 +/- 1.28 open (P = 0.016). Postoperative complication rates
      for the two groups were identical: two of 12 (ileus and post-operative bleeding).
      Tumor size mean was 6.8 +/- 2.99 cm for HALN versus 4.2 +/- 1.29 cm open (P =
      0.012). Tumor margins were negative for 12 of 12 in HALN versus 11 of 12 open.
      Selection bias (selecting ailing patients to the HALN cohort) diminished the
      statistical significance of our postoperative recovery data. It is likely that a
      prospectively randomized study with a larger population may prove the hand
      assisted approach equal if not superior to the open technique. The use of HALN in
      patients with renal tumors is an effective alternative to traditional
      transabdominal radical nephrectomy.

PMID- 11842962
TI  - Cardiac surgery after renal transplantation.
AB  - Renal transplantation remains a mainstay of therapy for end-stage renal disease.
      Cardiac disease has a high prevalence in this patient population. This study
      reviews the factors and outcomes associated with cardiac surgery in renal
      transplant recipients. We performed a retrospective review of all patients at our
      institution with a functioning renal allograft at the time of their cardiac
      surgical procedure. Between June 1971 and April 2000, 2343 patients underwent
      renal transplantation at Vanderbilt University Medical Center. Twenty-six
      patients with a functioning renal allograft subsequently underwent a cardiac
      procedure requiring cardiopulmonary bypass. There were 11 women and 15 men.
      Twenty-four patients underwent coronary bypass, one had a double valve
      replacement, and one had a combined coronary bypass/valve replacement. The
      interval from renal transplant to heart surgery ranged between 0.6 and 227 months
      (mean 79.1). Operative mortality was zero but there were two hospital deaths: one
      due to multisystem organ failure and one due to pulmonary embolism. Six
      additional patients died late with only one due to heart disease. Four patients
      required perioperative dialysis, and one of these went on to require permanent
      dialysis. Two additional patients returned to dialysis late postoperatively. The
      requirement for acute perioperative dialysis was predicted by preoperative
      creatinine, hematocrit, and intraoperative urine output. The overall survival is
      69 per cent (18 of 26) with a median follow-up of 38 months. The majority of long
      term survivors have minimal cardiac symptoms. Standard cardiac surgery procedures
      can be performed with relative safety in patients with functioning renal
      allografts. The incidence of perioperative and late development of renal failure
      requiring dialysis is low. The long-term survival and symptomatic improvement
      achieved are favorable and warrant continued performance of cardiac surgery in
      patients with functioning renal allografts.

PMID- 11842963
TI  - Withholding/withdrawal of life support in trauma patients: is there an age bias?
AB  - Our objective was to examine patterns of withholding/withdrawal (WH/WD) of life
      support in trauma patients and to determine whether WD/WH of life support is used
      more frequently in elderly patients. This is a retrospective cohort study of
      injured elderly (> or = 65 years) and young patients (< 65 years) from 1994
      through 1998 treated at a surgical intensive care unit in a community tertiary
      care hospital. We studied the cases of 82 patients (30 elderly and 52 young
      patients) with WH/WD of life support after injury. Our main outcome measures were
      demographic and clinical characteristics of elderly and young patients undergoing
      WH/WD of life support after injury with an association between age and WH/WD of
      life support. Of 102 total trauma patient deaths 82 had WH/WD of life support.
      This mode was chosen in 52 (80%) patients under the age of 65 and in 30 (81%)
      patients age 65 or greater. Patients in the younger cohort had a higher mean
      Injury Severity Score and Abbreviated Injury Score of 5 (P < 0.05). The elderly
      cohort had a higher incidence of pre-existing disease (< 0.001). Length of stay
      was similar between the populations. We conclude that the elderly were no more
      likely to have WH/WD of life support than were younger patients. However, the
      older patients were less severely injured as measured by Injury Severity Score
      and percentage with Abbreviated Injury Score head of 5. Other factors such as the
      presence of pre-existing disease may influence the decision to withhold or
      withdraw life support to a greater degree than the actual severity of injuries.

PMID- 11842964
TI  - Obesity: is there an increase in perioperative complications in those undergoing
      elective colon and rectal resection for carcinoma?
AB  - The hypothesis of this study was that obese and overweight patients undergoing
      elective resection for colon and rectal cancer have longer operative times,
      increased intraoperative blood loss, and more postoperative complications
      compared with normal-weight individuals. Our study cohorts included all patients
      undergoing elective first-time colon resection for proven colorectal carcinoma.
      Patients undergoing resection for recurrent disease or for emergent indications
      such as obstruction, perforation, or hemorrhage and those who underwent an
      additional surgical procedure at the time of colon resection were excluded from
      analysis. We conducted a retrospective chart review of all patients undergoing
      resection for colorectal carcinoma during a 30-month period. One hundred fifty
      three consecutive patients were identified. Body Mass Index was calculated for
      each patient. Each patient was labeled as normal, overweight, or obese on the
      basis of World Health Organization criteria. Estimated intraoperative blood loss,
      duration of surgery, and postoperative complications were recorded for each
      patient. Comparisons of continuous variables were made using one- or two-way
      analysis of variance testing. Comparisons of discrete variables were made with
      chi-square testing. Level of confidence was defined as P < 0.05. Forty-eight
      normal, 54 overweight, and 51 obese patients were identified. The type of colon
      resection, age range, and premorbid conditions were well matched between groups.
      There was no statistical difference in intraoperative blood loss between groups.
      The operative times were statistically longer in obese and overweight groups
      compared with the normal group. No statistical differences existed in
      postoperative complications between groups. We conclude that obese and overweight
      patients undergoing resection for colorectal carcinoma when compared with normal
      weight patients have similar intraoperative blood loss and postoperative
      complications but longer operative times.

PMID- 11842965
TI  - The impact of positive pressure ventilation on the diagnosis of traumatic
      diaphragmatic injury.
AB  - Initial chest radiography (CXR) has been noted to have limited diagnostic
      sensitivity to detect acute diaphragmatic injury (ADI). A further confounding
      variable may be intubation and positive pressure ventilation which may prevent
      herniation of abdominal organs until weaning is achieved. We sought to determine
      the impact of positive pressure ventilation on the sensitivity of the initial CXR
      to identify ADI as well as to document the incidence of late herniation occurring
      as positive pressure ventilation is weaned. A retrospective chart review of 166
      patients over an 8-year period in whom diagnosis of ADI was made on the same
      admission was performed. Etiology was penetrating trauma in 91 (55%). Eighty-five
      (51%) patients were intubated and ventilated with positive pressure before the
      initial chest radiograph. Diagnosis was made within 24 hours in 144 (87%) cases.
      The ability to correctly identify ADI by CXR was affected by whether or not the
      patient was intubated (intubated 12% vs nonintubated 27%; P = 0.001), side (right
      10% vs left 27%; p = 0.04), and injury size (> 5 cm 81% vs < or = 5 cm 3%, P =
      0.02). Late diagnosis was made in 22 cases: eight during surgery, six because of
      persistent radiographic abnormalities, and six when high levels of ventilator
      support were decreased with subsequent herniation of stomach above the diaphragm.
      Two cases were described at autopsy. Diaphragmatic injuries cannot be excluded if
      patients are intubated. Late diagnosis can be facilitated if chest radiographs
      are reviewed in sequence as ventilator support is decreased.

PMID- 11842967
TI  - Survey of resident training in robotic surgery.
AB  - Robotics has been recognized as a major driving force in the advancement of
      minimally invasive surgery. However, the extent to which General Surgery
      residents are being trained to use robotic technology has never been assessed. A
      survey was sent to program directors of accredited General Surgery training
      programs to determine the prevalence and application of robotics in surgical
      training programs. Responses were tabulated and analyzed. Thirty-three per cent
      indicated interest in minimally invasive surgery. Twelve per cent of responders
      have used robotics in their practice, and 65 per cent felt robotics will play an
      important role in the future of General Surgery. Currently residents from 14 per
      cent of the responding training programs have exposure to robotic technology, and
      residents from an additional 4 per cent of these programs have limited didactic
      exposure. Program directors from 23 per cent of responding programs identified
      plans to incorporate robotics into their program. Robotics have been shown to
      make standard endoscopic surgical procedures more efficient and cost-effective as
      well as allowing a variety of procedures that were only possible with
      conventional methods to be completed with minimally invasive techniques. This new
      technology promises to be a large part of the future of surgery and as such
      deserves more attention in the training of General Surgery residents.

PMID- 11842966
TI  - Spontaneous infarction of a parathyroid adenoma: two case reports and review of
      the literature.
AB  - The spontaneous infarction of a parathyroid adenoma is an uncommon event,
      although it has been previously described. Patients may present symptomatically
      or experience resolution of their hyperparathyroidism. As such the appropriate
      clinical management of these patients remains unclear. We present two cases of
      spontaneous infarction of parathyroid adenomas. The first presented with neck
      pain and dysphagia and experienced at least temporary resolution of her
      hyperparathyroidism. The second patient experienced a fall in his parathyroid
      hormone and calcium levels before neck exploration. Infarcted parathyroid adenoma
      was diagnosed on pathologic evaluation of the surgical specimen. Inflammation
      surrounding the infarcted adenoma provided for a technically difficult operation.
      Although resolution of hyperparathyroidism has been described postinfarction, a
      regeneration of the parathyroid adenoma may occur. Therefore neck exploration and
      parathyroidectomy should still be considered. We propose a period of observation
      after diagnosis of spontaneous parathyroid adenoma infarction to avoid these
      acute inflammatory changes that have been described.

PMID- 11842968
TI  - Impact of a voluntary trauma system on mortality, length of stay, and cost at a
      level I trauma center.
AB  - Trauma systems have been shown to decrease injury-related mortality; however,
      their development has been slow often requiring legislative codification. The
      purpose of this study was to evaluate the impact of a voluntary regional trauma
      system on outcomes at a Level I trauma center. We conducted a retrospective
      cohort study in an American College of Surgeons-verified Level I trauma center
      including all patients admitted to a Level I trauma center during the periods
      April 1995 through March 1996 (T-1) and April 1997 through March 1998 (T-2). Our
      main outcome measures were in-hospital mortality, hospital length of stay, cost
      of care Compared with T-1 patients T-2 patients had lower mortality (odds ratio
      0.48, 95% confidence interval 0.32-0.71). A similar decline in mortality was
      observed for the entire six-county region compared with the remainder of the
      state. Among the most severely injured patients (Injury Severity Score > or = 16)
      T-2 patients had a shorter length of stay (16.5 vs 19.5 days; P < 0.05) and lower
      mean cost of care ($29,795 vs $34,983; P < 0.05). A voluntary trauma system can
      be implemented without the need for legislative mandate. After system
      implementation patient and financial outcomes were improved at an individual
      Level I trauma center.

PMID- 11842969
TI  - Percutaneous removal of spilled gallstones in a subhepatic abscess.
AB  - Abscess formation from spilled gallstones after laparoscopic cholecystectomy is
      infrequent. However, if an abscess does form and contains the spilled stones
      simple percutaneous drainage will not resolve the dilemma of a recurrent abscess.
      Open drainage has previously been recommended to remove the retained stones and
      decrease recurrent abscess formation. We report two cases in which the retained
      stones within an abscess were successfully removed using a percutaneous minimally
      invasive urological technique.

PMID- 11842970
TI  - Endoscopically placed nasogastrojejunal feeding tubes: a safe route for enteral
      nutrition in patients with hepatic encephalopathy.
AB  - Patients with hepatic encephalopathy are at particular risk for aspiration when
      given oral or gastric feedings. An ideal strategy might combine distal enteral
      feeding with proximal gastric decompression, which is offered by a
      nasogastrojejunal (NGJ) feeding tube. One objective was to determine the efficacy
      and safety of endoscopically placed NGJ feeding tubes in patients with hepatic
      encephalopathy. Charts of patients who underwent NGJ tube placements between
      April 1997 and January 2000 were retrospectively reviewed. Two endoscopic
      techniques ("push" and "pull") were used. Eighteen patients (nine male and nine
      female) underwent 32 procedures. Twelve patients had undergone liver
      transplantation, four had decompensated cirrhosis, and two had fulminant hepatic
      failure. Twenty procedures used the push technique and 12 required the pull
      technique. The insertion time was shorter for the push technique compared with
      the pull technique (21.8 vs 39.6 min, P < 0.05). Enteral feedings were begun at
      an average of 5.2 hours after tube placement. The tubes remained in place for an
      average of 13.9 days. Complications related to the NGJ tubes included self
      removal in eight, tube clogging in five, proximal migration in four, and
      intraduodenal migration of the gastric port in one. No aspiration episodes
      occurred. We conclude that NGJ feeding tubes may be placed endoscopically as a
      bedside procedure for patients with hepatic encephalopathy and provide a safe,
      efficacious, and rapid route for enteral nutrition in these patients.

PMID- 11842972
TI  - Gynecomastia: complications of the subcutaneous mastectomy.
AB  - Gynecomastia is a benign enlargement of the male breast secondary to gland
      proliferation. Subcutaneous mastectomy is performed for symptomatic patients and
      in those desiring cosmetic changes. The aim of this study was to assess the risk
      factors and complications associated with the operation. We retrospectively
      examined the records of all patients undergoing a subcutaneous mastectomy for
      gynecomastia. Ninety-one patients were identified. We conducted telephone
      interviews with 52 patients and performed 65 subcutaneous mastectomies on those
      52 patients. Thirty of the 65 procedures (46%) developed complications. These
      included sensory changes, pain, seromas, scarring, breast asymmetry, hematomas,
      and wound infection. No preoperative risk factors were significant for
      postoperative complications. Eighteen of 22 cases with drains placed
      intraoperatively developed complications as compared with 12 of 43 cases without
      drains (P = 2.6 x 10(-7)). Specimens removed from the patients who had drains
      placed were significantly larger than those from patients who did not have drains
      placed (P = 1.5 x 10(-5)). However, specimen size was not an independent risk
      factor for development of a complication (P = 0.14). We found a relatively high
      complication rate in subcutaneous mastectomy for gynecomastia. Most complications
      are minor with no long-term effect. Drain placement was the only risk factor
      associated with postoperative complications.

PMID- 11842971
TI  - Urachal carcinoma: key points for the general surgeon.
AB  - Urachal carcinoma is a rare neoplasm with the majority of cases reported in the
      urologic literature. Because of its presentation as an intra-abdominal mass with
      involvement of adjacent structures the general surgeon may be consulted early in
      the diagnostic evaluation. One should be aware of this entity as early
      recognition and appropriate surgery provides the best opportunity for long-term
      survival. Herein we describe a typical case, appropriate evaluation, and review
      of the literature.

PMID- 11842973
TI  - Re: Routine perioperative pulmonary artery catheterization has no effect on rate
      of complications in vascular surgery: a meta-analysis.

PMID- 11842974
TI  - Hutchinson-Gilford progeria syndrome: a pathologic study.
AB  - Hutchinson-Gilford progeria syndrome is an extremely rare condition with features
      of premature and accelerated aging. The pattern of inheritance if unclear,
      although both autosomal recessive and autosomal dominant modes have been
      proposed. The children usually present in late infancy and early childhood with a
      characteristic phenotype of alopecia; short stature; abnormal skin, teeth, and
      nails; beaked nose; loss of subcutaneous fat; and failure to thrive. This
      condition has been reported on all inhabited continents and has been described in
      all major races. Laboratory findings note an increased urinary excretion of
      hyaluronic acid. Death results from cardiovascular abnormalities in the majority
      of cases and usually occurs in the second decade of life. There is no effective
      treatment. We report the pathologic changes noted at autopsy on a 20-year-old
      woman with classic features of Hutchinson-Gilford progeria syndrome.

PMID- 11842975
TI  - Nephroblastoma. DNA characteristics and their modifications induced by
      prenephrectomy chemotherapy: a cytofluorimetric study.
AB  - Treatment of nephroblastoma (Wilms' tumor) has presently achieved a 90% survival
      rate. Stage and grade are considered the most reliable prognostic parameters, but
      other biological factors are under study in order to improve patient
      stratification. Deoxyribonucleic acid (DNA) ploidy has been suggested to be
      useful in this setting. We retrospectively studied 79 patient with nephroblastoma
      (58 pretreated with chemotherapy and 21 not pretreated) by means of flow
      cytometry. DNA content and synthetic phase values were correlated with pathologic
      features and outcome. DNA modifications induced by chemotherapy were
      investigated. Sixty-nine tumors were diploid and 10 aneuploid. DNA content did
      not correlate with clinical course and was not modified by pretreatment.
      Aneuploid tumors were restricted to lower stages. Mean S-phase rate was lower and
      did not vary according to histology in pretreated tumors, while it was higher and
      increased with grade (p = 0.007) in previously untreated tumors. The fraction of
      cells in synthetic activity was related to outcome: Patients whose tumors
      displayed higher S-phase rates had a more favorable clinical course. Ploidy did
      not appear to be of prognostic significance. S-phase rate decreased after
      chemotherapy (p = 0.0002) and was related to survival. The worse outcome of
      pretreated patients might be attributed to a minor sensitivity to postoperative
      treatment: Preoperative chemotherapy would decrease the cell proliferation and
      might select resistant cellular clones of (possible) neoplastic residues.

PMID- 11842976
TI  - Acute liver disease and aplastic anemia associated with the persistence of B19
      DNA in liver and bone marrow.
AB  - We observed a 12-year-old boy with acute hepatitis and associated aplastic anemia
      (AA), where parvovirus B19 genome was repeatedly detected in liver and bone
      marrow biopsies, but not in blood samples. We conclude that: (1) B19 infection
      may be underdiagnosed as the causative agent responsible for acute hepatitis and
      associated AA if no organ-specific diagnostic tests are applied; (2) B19
      deoxyribonucleic acid (DNA) can persist in the liver; (3) during the acute phase
      of hepatitis, extramedullary hematopoiesis may be involved in the susceptibility
      for hepatic B19 infection.

PMID- 11842977
TI  - T and B cell repertoire in gastric lymph follicles in children with Helicobacter
      pylori infection.
AB  - Helicobacter pylori infection has been implicated in the development of
      gastrointestinal malignancy in adults and children. The histopathological
      processes that lead to such development are unknown. We compared the immune cell
      repertoire of mucosal lymph follicles in children with H. pylori infection to B
      cell type mucosal associated lymphoid tissue (MALT)-lymphoma of adults. The B and
      T cell populations residing within the lymph follicles and/or within B cell type
      MALT lymphoma were characteriZed by an immunohistochemical technique, utilizing B
      and T cell markers including: CD3, CD4, CD8 (T cells); CD20, CD40, GD74, BLA36,
      CD80, CD86 (B cells). Stain intensity was compared between the samples. T cell
      repertoire was observed within the lymph follicles, but not in the B cell MALT
      lymphoma specimens. No significant difference was observed between the staining
      of CD40, CD74, CD8, and BLA36. The B cell markers, CD80 and CD86, were found
      within the centrocytic zone of the lymph follicle. In the B cell repertoire, no
      significant difference was observed between the lymph follicles of children with
      H. pylori infection and the adult MALT-lymphoma specimens except in CD20. B and T
      cells were in close anatomical proximity, enabling them to interact and exchange
      immunological information.

PMID- 11842978
TI  - Follicular bronchiolitis associated with Legionella pneumophilia infection.
AB  - An 8-month-old girl with respiratory distress and stridor was admitted to our
      hospital. Two days later, she died of respiratory insufficiency due to pneumonia.
      Autopsy confirmed the presence of follicular bronchiolitis (FBB) in both lungs.
      After consideration of her clinical course, we focused on three pathogens:
      Legionella pneumophilia, Pneumocystis carinii, and Mycobacterium tuberculosis.
      Only Legionella pneumophilia was detected by both immunohistochemistry and
      polymerase chain reaction.

PMID- 11842979
TI  - Inflammatory myofibroblastic tumor of the gastroesophageal junction in childhood.
AB  - We report a unusual case of an inflammatory myofibroblastic tumor arising at the
      gastroesophageal junction in a 14-year-old girl. The bland histologic appearance
      with concurrent infiltration into adjacent structures made diagnostic
      interpretation difficult, but suggested a neoplastic process. A literature review
      was undertaken to address diagnostic and management issues raised in this case.
      Although the anatomic location was unusual, clinical, grass, histopathologic, and
      immunohistochemical data substantiated the diagnosis of inflammatory
      myofibroblastic tumor. The bland histologic appearance was consistent with the
      most widely accepted view of inflammatory myofibroblastic tumor as a low-grade
      neoplasm. Wide surgical excision was performed. This is considered the preferred
      treatment given the potential risk of recurrence and aggressive behavior, most
      frequently noted with extrapulmonary disease. Although inflammatory
      myofibroblastic tumor represents an heterologous spectrum of benign to malignant
      neoplastic proliferations, the prognosis is good in casts with benign histologic
      features.

PMID- 11842980
TI  - Pathology teach and tell: chondroblastoma.

PMID- 11842982
TI  - Enterococcal bacteremia in cancer patients.

PMID- 11842981
TI  - Pathology teach and tell: neonatal infective endocarditis.

PMID- 11842983
TI  - Recommendations for preventing hepatitis C virus infection: analysis of a
      Brooklyn endoscopy clinic's outbreak.

PMID- 11842984
TI  - Legionella in the hospital water supply: a plea for decision making based on
      evidence-based medicine.

PMID- 11842985
TI  - Presence and chromosomal subtyping of Legionella species in potable water systems
      in 20 hospitals of Catalonia, Spain.
AB  - OBJECTIVE: To investigate the presence and clonal distribution of Legionella
      species in the water supply of 20 hospitals in Catalonia, Spain. SETTING: 20
      hospitals in Catalonia, an area of 32,000 km2, located in northeast Spain.
      METHODS: Environmental cultures of 186 points of potable water supply and 10
      cooling towers were performed for the presence of Legionella species. Following
      filtration and acid treatment, the samples were seeded in selective MWY (modified
      Wadowsky Yee)-buffered charcoal yeast extract-alpha agar. All isolates obtained
      were characterized microbiologically and genotyped by SfiI pulsed-field gel
      electrophoresis (PFGE). RESULTS: 73 of 196 water samples, representing 17 of the
      20 hospitals included in the study, were positive for Legionella pneumophila
      (serogroups 1, 2-14, or both). The degree of contamination ranged from 200 to
      74,250 colony-forming units/L. Twenty-five chromosomal DNA subtypes were detected
      by PFGE. A single DNA subtype was identified in 10 hospitals, 2 DNA subtypes were
      observed in 6 hospitals, and 1 hospital exhibited 3 different DNA subtypes. Each
      hospital had its own Legionella DNA subtype, which was not shared with any other
      hospitals. CONCLUSIONS: Legionella was present in the water of most of the
      hospitals studied; each such hospital had a unique, dominant chromosomal DNA
      subtype. The verification of several genomic DNA restriction profiles in such a
      small geographic area demonstrates the great genetic diversity of Legionella in
      the aquatic environment.

PMID- 11842986
TI  - Surveillance and control of methicillin-resistant Staphylococcus aureus
      infections in French hospitals.
AB  - OBJECTIVE: To assess the way French hospitals conduct surveillance for, and
      control infections caused by, methicillin-resistant Staphylococcus aureus (MRSA),
      and to evaluate the incidence of these infections. DESIGN: Retrospective analysis
      of sample surveillance data. SETTING: Representative sample of French hospitals.
      PARTICIPANTS: Representative sample of 38 French public hospitals. METHODS:
      Hospitals were selected randomly in 1996, taking into account their location and
      number of beds. Administrative data, surveillance denominators used,
      antimicrobial resistance rates, and infection control practices were analyzed for
      the period 1990 to 1995. The same 38 centers were contacted 3 years later, in
      1998, to reassess their surveillance and control activities. RESULTS: French
      hospitals were slow to implement MRSA surveillance programs; only 5% had such
      programs in 1990, when the median incidence per admission (0.37%) and per patient
      days (0.04%) of MRSA infections was already high. Despite the implementation of
      surveillance programs in 66% of French hospitals in 1995 and 87% in 1998, the
      MRSA infection rates remained stable from 1990 to 1995 and increased from 1995 to
      1998. The proportion of French hospitals having a policy for the transfer of MRSA
      infected patients to other hospitals increased from 47% in 1995 to 61% in 1998,
      whereas screening for MRSA colonization (42%-53%) and isolation for colonized or
      infected patients (87%-89%) remained stable. CONCLUSIONS: This first national
      survey showed that French hospitals probably were not optimally prepared to
      control and prevent MRSA infections, since they were slow to respond to the
      growing problem.

PMID- 11842988
TI  - Colonization with methicillin-resistant Staphylococcus aureus in ICU patients:
      morbidity, mortality, and glycopeptide use.
AB  - OBJECTIVE: To determine the impact of methicillin-resistant Staphylococcus aureus
      (MRSA) colonization on the occurrence of S. aureus infections (methicillin
      resistant and methicillin-susceptible), the use of glycopeptides, and outcome
      among intensive care unit (CU) patients. DESIGN: Prospective observational cohort
      survey. SETTING: A medical-surgical ICU with 10 single-bed rooms in a 460-bed,
      tertiary-care, university-affiliated hospital. PATIENTS: A total of 1,044 ICU
      patients were followed for the detection of MRSA colonization from July 1, 1995,
      to July, 1 1998. METHODS: MRSA colonization was detected using nasal samples in
      all patients plus wound samples in surgical patients within 48 hours of admission
      or within the first 48 hours of ICU stay and weekly thereafter. MRSA infections
      were defined using Centers for Disease Control and Prevention standard
      definitions, except for ventilator-associated pneumonia and catheter-related
      infections, which were defined by quantitative distal culture samples. RESULTS:
      One thousand forty-four patients (70% medical patients) were included in the
      analysis. Mean age was 61+/-18 years; mean Simplified Acute Physiologic Score
      (SAPS) II was 36.4+/-20; and median ICU stay was 4 (range, 1-193) days. Two
      hundred thirty-one patients (22%) died in the ICU. Fifty-four patients (5.1%)
      were colonized with MRSA on admission, and 52 (4.9%) of 1,044 acquired MRSA
      colonization in the ICU. Thirty-five patients developed a total of 42 S. aureus
      infections (32 MRSA, 10 methicillin-susceptible). After factors associated with
      the development of an S. aureus infection were adjusted for in a multivariate Cox
      model (SAPS II >36: hazard ratio [HR], 1.64; P=.09; male gender: HR, 2.2; P=.05),
      MRSA colonization increased the risk of S. aureus infection (HR, 3.84; P=.0003).
      MRSA colonization did not influence ICU mortality (HR, 1.01; P=.94).
      Glycopeptides were used in 11.4% of the patients (119/1,044) for a median
      duration of 5 days. For patients with no colonization, MRSA colonization on
      admission, and ICU-acquired MRSA colonization, respectively, glycopeptide use per
      1,000 hospital days was 37.7, 235.2, and 118.3 days. MRSA colonization per se
      increased by 3.3-fold the use of glycopeptides in MRSA-colonized patients, even
      when an MRSA infection was not demonstrated, compared to non-colonized patients.
      CONCLUSIONS: In our unit, MRSA colonization greatly increased the risk of S.
      aureus infection and of glycopeptide use in colonized and non-colonized patients,
      without influencing ICU mortality. MRSA colonization influenced glycopeptide use
      even if an MRSA infection was not demonstrated; thus, an MRSA control program is
      warranted to decrease vancomycin use and to limit glycopeptide resistance in gram
      positive cocci.

PMID- 11842987
TI  - Changing pattern of antibiotic resistance in methicillin-resistant Staphylococcus
      aureus from German hospitals.
AB  - OBJECTIVE: To investigate the background of changes of resistance phenotypes in
      methicillin-resistant Staphylococcus aureus (MRSA) from nosocomial infections in
      German hospitals by molecular typing and identification of particular resistance
      genes. METHODS: Isolates from the network for monitoring the spread of MRSA in
      Germany were subjected to quantitative susceptibility testing, to molecular
      typing, and to polymerase chain reaction identification of resistance genes.
      PARTICIPANTS: The network consists of 175 German clinical microbiological
      laboratories collaborating with the German Reference Center for Staphylococci,
      which performs typing of staphylococcal isolates from nosocomial infections and
      data analysis. RESULTS: During the past 5 years, MRSA susceptible to other
      antibiotics such as oxytetracycline, erythromycin, and gentamicin became more
      frequent. The proportion of epidemic MRSA clones that had been disseminated in
      the past and that exhibited broad resistance phenotypes decreased, whereas the
      proportion of recently emerging MRSA carrying only a few other resistance
      determinants has increased (1994, 11.5%; 1998, 39%). CONCLUSIONS: The changing
      pattern of resistance phenotypes of MRSA from nosocomial infections in Germany is
      mainly due to the spread of recently emerging epidemic strains that are less
      frequently resistant to antibacterials other than oxacillin. The observed changes
      cannot simply be attributed to overall antibiotic consumption.

PMID- 11842989
TI  - Association between hospital-acquired infections and patients' transfers.
AB  - OBJECTIVE: To assess the risk of nosocomial infection in transferred patients and
      to determine whether transfer is only a risk marker or is independently
      associated with nosocomial infection. DESIGN: Retrospective analysis. SETTING: A
      400-bed general hospital in the Paris area. PATIENTS: All the patients
      hospitalized on the days of the surveys were included. METHODS: Epidemiological
      analysis of data collected in four annual nosocomial infection prevalence surveys
      conducted between 1993 and 1996. RESULTS: Of the 1,326 patients included in the
      four surveys, 70 (5.3%) had been transferred from another hospital and 199
      (15.0%) from another ward of our hospital. Transferred patients more frequently
      had known risk factors of nosocomial infection: age >65 years (P<10(-5)), a
      length of hospital stay >7 days on the day of the survey (P<10(-6)), at least one
      invasive procedure (34.2% vs 27.2%; P<.05), a recent surgical intervention
      (P<.05), and an immunosuppression (P<.01). The prevalence rate of infected
      patients was 6.7% (95% confidence interval, 5.3-8.1). The risk of being infected
      on a given day was more than 4 times higher in transferred patients (P<10(-6));
      however, the risk was similar between patients transferred from another hospital
      (20.0%) and patients transferred within the hospital (17.1%). The multivariate
      analysis performed by logistic regression showed that intrahospital transfer, a
      length of hospital stay >7 days, and having had at least one invasive procedure
      were independent risk factors of infection. CONCLUSION: According to this study,
      patient transfer is both a risk marker (associated with several known risk
      factors) and independently associated with nosocomial infection. The origin of a
      transferred patient is readily known at admission. It would be useful to adopt
      specific measures for such patients, particularly if they have other risk factors
      of nosocomial infection, both to protect them and to prevent transmission of the
      infection to other hospitalized patients.

PMID- 11842990
TI  - Transmission of hepatitis C in a pharmacologic study.
AB  - OBJECTIVE: To describe an outbreak of hepatitis C in a clinical research study.
      DESIGN: Observational study. SETTING: Tertiary-care hospital. PATIENTS:
      Healthcare workers who volunteered to be subjects in a study of the metabolic
      effects of inhaled and oral corticosteroids who were unwittingly exposed to
      hepatitis C virus (HCV). METHODS: Epidemiological investigation and serological
      analyses. RESULTS: One chronic carrier of HCV was identified. Four fellow workers
      volunteering in the studies became infected with HCV, with 96% homology among
      strains. There was no evidence of spread from infected healthcare workers to
      patients on whom they had performed arterial punctures (2 of 214 positive,
      unrelated to each other and to the outbreak strain). CONCLUSION: Infection
      control standards in clinical research must be maintained vigorously to prevent
      transmission of blood-borne pathogens such as HCV.

PMID- 11842991
TI  - Hepatitis C in a ward for cystic fibrosis and diabetic patients: possible
      transmission by spring-loaded finger-stick devices for self-monitoring of
      capillary blood glucose.
AB  - OBJECTIVE: To identify the routes of transmission in a nosocomial outbreak of
      hepatitis C virus (HCV) infection. DESIGN: Epidemiological investigation,
      including screening for HCV of hospitalized patients, and a retrospective cohort
      study, review of hygiene and medical practices, and molecular comparison of HCV
      isolates. SETTING: A specialized care unit for cystic fibrosis (CF) and diabetic
      patients at an acute-care facility in the south of France. RESULTS: Of the 57 CF
      patients (age in 1995: 2-28 years), 38 (66.7%) were tested and 22 (57.9%) were
      anti-HCV positive. Eight (50%) of 16 patients with anti-HCV antibody tested by
      polymerase chain reaction were viremic. No patients had received blood products
      or had any history of intravenous drug use. All 18 (100%) patients with CF who
      had ever undergone self-monitoring of capillary blood glucose in the unit were
      anti-HCV positive, compared to 4 (20%) of 20 who had not (relative risk, 5.0; 95%
      confidence interval, 2.1-12.0). Seventy (39.5%) of the patients with diabetes
      were screened for anti-HCV; 12 (18.8%) tested positive, with 3 (25%) positive for
      HCV-RNA. Patients with diabetes had routine capillary blood glucose monitoring
      while hospitalized and shared with CF patients the same spring-triggered devices
      for capillary blood glucose monitoring. The disposable platform of the devices
      was not changed between patient use. All HCV isolates belonged to the type 1,
      subtype b, and phylogenetic analysis showed a close homology by sequencing of
      NS5b and E2/HVR regions. CONCLUSION: As reported earlier for the hepatitis B
      virus, shared spring-triggered devices for capillary blood glucose monitoring by
      finger puncture may transmit HCV. Strict application of Standard Precautions
      procedures is warranted in any healthcare setting.

PMID- 11842992
TI  - Proportion of hospital deaths potentially attributable to nosocomial infection.
AB  - OBJECTIVE: To determine the fraction of hospital deaths potentially associated
      with nosocomial infection (NI). DESIGN: A matched (1:1) case-control study.
      SETTING: An 800-bed, tertiary-care, teaching hospital. PATIENTS: All patients
      older than 14 years who were admitted to the hospital between January 1, 1990,
      and January 1, 1991, were eligible. All 524 consecutive deaths that occurred in
      the hospital comprised the case group. For each case, a control patient was
      matched for primary admission diagnosis and admission date. OUTCOME MEASURES: The
      proportion of hospital deaths potentially associated with NI was estimated from
      the population attributable risk (PAR) adjusted for age, gender, service,
      severity of illness, length of stay, and quality of the medical record. RESULTS:
      For stays longer than 48 hours, the PAR for all NIs was estimated to be 21.3%
      (95% confidence interval [CI95], 16.8%-30.5%). The greatest proportion of deaths
      potentially associated with NIs was observed in patients with only one infection
      (PAR, 15.0%; CI95, 10.9%-22.6%) and bacteremia or sepsis (PAR, 7.7%; CI95, 4.6%
      11.6%). CONCLUSIONS: NIs are associated with a large proportion of intrahospital
      deaths. This information may help clinicians and healthcare managers to assess
      the impact of programs for the prevention and control of NIs on intrahospital
      death.

PMID- 11842993
TI  - Hospital management of tuberculosis in a region with a low incidence of
      tuberculosis and a high prevalence of nontuberculous mycobacteria.
AB  - We prospectively assessed the management of patients with suspected tuberculosis
      (TB) in an area with a high prevalence of nontuberculous mycobacteria (NTM) and a
      low incidence of TB. Clinicians' assessments were sensitive for TB but had poor
      predictive value. The acid-fast smear was a weak predictor of TB, owing to a high
      rate of isolation of NTM.

PMID- 11842994
TI  - Environmental contamination by multidrug-resistant Acinetobacter baumannii in an
      intensive care unit.
AB  - Contamination in an intensive care unit caused by multidrug-resistant
      Acinetobacter baumannii complex (MRAB)-colonized patients was evaluated using
      environmental and patient cultures. MRAB occurred in 21% of patients' cultures,
      2.1% of 513 areas surrounding MRAB-patients, and one of 372 common areas. No
      transmission to other patients occurred. Barrier precautions and ethanol
      disinfection may prevent dissemination.

PMID- 11842995
TI  - Presence of polyclonal Pseudomonas aeruginosa in an intensive care unit: a 27
      month prospective study on molecular epidemiology.
AB  - Pseudomonas aeruginosa was isolated in 22.2% of 305 intensive care unit
      environmental cultures. A high genetic heterogeneity (18 pulsotypes) was evident.
      Taps and related surfaces were a stable reservoir for certain pulsotypes. The
      15.4% of the P. aeruginosa-positive cultures were polyclonal. Different colony
      morphotypes should be assayed in surveillance studies.

PMID- 11842996
TI  - Multiresistant extended-spectrum beta-lactamase-producing Klebsiella pneumoniae
      causing an outbreak of nosocomial bloodstream infection.
AB  - This article describes an outbreak of bloodstream infection due to clonal
      dissemination of multiresistant Klebsiella pneumoniae in a neonatal area, during
      August 1999, in Mexico City General Hospital. The intestinal tract was the likely
      reservoir, and intensification of Contact Precaution measures contained the
      outbreak.

PMID- 11842997
TI  - Outbreak of nosocomial sepsis and pneumonia in a newborn intensive care unit by
      multiresistant extended-spectrum beta-lactamase-producing Klebsiella pneumoniae:
      high impact on mortality.
AB  - We describe a case-control study of a small outbreak of nosocomial sepsis and
      pneumonia with high mortality due to clonal dissemination of a multiresistant
      Klebsiella pneumoniae in the neonatal intensive care unit of a Mexican
      institution. Our study helped to change nosocomial infection control policy in
      this hospital.

PMID- 11842998
TI  - High-density lipoproteins: effects of alcohol, estrogen, and phytoestrogens.
AB  - Plasma high-density lipoproteins (HDL) play an important role in the reverse
      cholesterol transport pathway. Factors affecting plasma HDL levels may be
      important, therefore, in the prevention of cardiovascular disease. Among the
      lifestyle and environmental factors that have been shown to increase HDL
      cholesterol are moderate alcohol intake and estrogen administration.
      Phytoestrogens, molecules of plant origin that resemble estrogen and act as weak
      estrogens, do not have a clear effect on HDL cholesterol. The molecular
      mechanisms of action of alcohol, estrogen, and phytoestrogens on HDL are under
      investigation.

PMID- 11842999
TI  - The history and future of food fortification in the United States: a public
      health perspective.
AB  - For more than 50 years, the United States federal government has regulated food
      fortification. During this time, the nutritional situation in the United States
      has improved greatly, whereas scientific information about the role of vitamins
      and minerals in human growth and development has increased exponentially.
      Concurrently, government authority to regulate food fortification has declined.
      This paper provides a brief history of U.S. food fortification policy and
      describes the contribution of food fortification to U.S. nutrient intakes. The
      paper highlights future directions of food fortification in the United States in
      light of these important developments, and addresses the issue of risk and the
      need to balance deficiency and toxicity in a generally well nourished population.

PMID- 11843000
TI  - Obesity is not protective for bones in childhood and adolescence.
AB  - Although body weight is considered to positively affect bones of children and
      adults, recent studies suggest that overweight and obesity in childhood and
      adolescence reduce bone mineral content below what would be predicted based on
      weight and are associated with an increase in incidence of childhood fractures.

PMID- 11843001
TI  - The babel of the ABCs: novel transporters involved in the regulation of sterol
      absorption and excretion.
AB  - Hypercholesterolaemia is a major risk factor for coronary heart disease (CHD).
      Therefore, the reduction of low-density lipoprotein (LDL) cholesterol is one of
      the primary targets of the current recommendations to decrease CHD risk in the
      population. Whereas, the mechanisms involved in de novo cholesterol synthesis and
      its uptake by cells via the LDL receptor are well known, we still need better
      understanding about the mechanisms involved in intestinal cholesterol absorption
      and excretion. The recent discovery of ABCG5 and ABCG8 transporters will
      significantly improve our understanding of cholesterol trafficking and it will
      lead to better and new therapeutic strategies to maintain cholesterol
      homeostasis.

PMID- 11843002
TI  - Does vitamin C intake slow the progression of gastric cancer in Helicobacter
      pylori-infected populations?
AB  - Vitamin C's role in the prevention of disease and malignancy has been studied
      over the last several decades. Vitamin C intake has been shown to have an inverse
      relationship with gastric cancer. Recent follow-up studies on high-risk
      populations suggest that ascorbic acid, the reduced form of vitamin C, protects
      against gastric cancer, for which H. pylori is a significant risk factor. In
      populations infected with H. pylori, there is a reduction in gastric juice
      ascorbic acid concentration. This article reviews the risk factors for gastric
      cancer and the role of vitamin C in prevention of the disease.

PMID- 11843003
TI  - Modulation of monocyte-macrophage function with alpha-tocopherol: implications
      for atherosclerosis.
AB  - Cardiovascular disease is the leading cause of morbidity and mortality in the
      Western world. Monocyte-macrophages are crucial cells in atherogenesis. Several
      lines of evidence suggest that antioxidants, especially alpha-tocopherol, have
      beneficial effects with regard to cardiovascular disease. Alpha-tocopherol has
      beneficial effects on cell functions that are pivotal in atherogenesis. Alpha
      tocopherol inhibits platelet aggregation and proinflammatory activity of
      monocytes. In vitro data also support an effect of alpha-tocopherol on smooth
      muscle cell proliferation and endothelial function. Finally, recent data support
      an effect of alpha-tocopherol on macrophage function. The mounting evidence from
      in vitro and in vivo studies provides a sound scientific basis for alpha
      tocopherol supplementation. Further clinical trials are required, however, before
      a definitive recommendation can be made for primary and secondary prevention of
      heart disease.

PMID- 11843004
TI  - A call for honesty.

PMID- 11843005
TI  - Unusual medieval dental abrasion.

PMID- 11843006
TI  - Assessing quality control.

PMID- 11843007
TI  - Bilateral temporomandibular joint pseudogout.
AB  - Pseudogout is an acute presentation of one type of crystal deposition disease in
      which calcium pyrophosphate dihydrate crystals are found in the joint spaces of
      synovial joints. In this case, a 56-year-old caucasian male presented with right
      sided preauricular swelling, temporomandibular joint arthralgia and restricted
      mouth opening; he developed identical symptoms on the left side two days later.

PMID- 11843008
TI  - NHS dental treatment.

PMID- 11843009
TI  - Ehlers Danlos syndrome.

PMID- 11843010
TI  - Female discrimination?

PMID- 11843011
TI  - Vacant posts reported in dental practice: implications for human resource
      planning.
AB  - OBJECTIVES: To describe the proportion of dental practitioners who report
      vacancies within their dental practice for the following: dental surgeons, dental
      hygienists, dental nurses and dental receptionists. To determine the proportion
      of dental practitioners working in general dental practice who would consider
      employing a dental therapist. METHOD: Analysis of data from the British Dental
      Association Omnibus Survey 2000. The sample comprised 992 qualified dentists in
      all fields of practice. FINDINGS: The most commonly reported vacancies were for
      dental surgeons (18% of practitioners reported vacancies), dental nurses (17%)
      and dental hygienists (12%). Approximately 46% of general dental practitioners
      reported that they would employ a dental therapist if legislation permitted. The
      main reason for not employing a dental therapist was insufficient space in the
      dental practice. CONCLUSIONS: A large number of vacancies exist for dental
      surgeons, dental nurses and dental hygienists in the United Kingdom. Around half
      of dental practices express an interest in employing dental therapists should
      legislation permit.

PMID- 11843013
TI  - Electronic future of dentistry.

PMID- 11843012
TI  - General dental practitioners' beliefs on the perceived effects of and their
      preferences for remuneration mechanisms.
AB  - OBJECTIVE: To identify GDPs preferences for differing remuneration mechanisms and
      their beliefs on the effect of the mechanisms in care provision. DESIGN: Postal
      questionnaire survey of 300 GDPs holding an NHS contract with a London Health
      Authority. RESULTS: GDPs perceive that remuneration mechanisms are important in
      determining the provision of care but not overall disease levels. There were
      differences in the preferred remuneration mechanisms when working under the NHS
      compared with the non-NHS sector. When providing care under the NHS, either the
      current remuneration system or a salaried plus bonus would be the preferred
      choice, while for non-NHS care a fee-per-item mechanism is preferred. Fee-per
      item arrangement was the preferred choice of younger general practitioners
      compared with older practitioners. Females showed a greater preference for a
      salaried with bonus arrangement compared with males. CONCLUSIONS: If policy
      makers are to use remuneration mechanisms to influence the provision of care
      effectively, the beliefs that care providers hold about various mechanisms are
      important to understand how they would respond to changes in the system.

PMID- 11843014
TI  - Parvovirus B19 in pregnancy.
AB  - Parvovirus B19 is a common, self-limiting, usually benign childhood virus that
      causes erythema infectiosum, also known as fifth disease. Acute infection in
      pregnancy can cause B19 infection in the fetus, leading to nonimmune fetal
      hydrops or fetal loss, depending on gestational age at the time of infection.
      Susceptibility to parvovirus B19 infection should be determined in selected
      pregnant women at high risk for exposure, and counseling should be provided
      regarding prevention, testing, and treatment options if exposed.

PMID- 11843015
TI  - Breastfeeding policy.

PMID- 11843016
TI  - Breastfeeding initiation and duration: a 1990-2000 literature review.
AB  - OBJECTIVE: To review the literature on breastfeeding initiation and duration and
      to delineate effective strategies for promoting positive breastfeeding behaviors.
      DATA SOURCES: Computerized searches on MEDLINE, CINAHL, and the Cochrane Library.
      STUDY SELECTION: Articles from indexed journals relevant to the objective and
      published after 1990 (except for classic findings) were reviewed. Although a
      myriad of pertinent articles was located, referenced citations were limited to
      three per point. When article selection was required for a specific point,
      preferences were given to (a) randomized controlled trials; (b) meta-analyses;
      (c) studies with the largest, most representative samples; and (d) investigations
      conducted in North America. DATA EXTRACTION: Data were extracted and organized
      under the following headings: benefits of breastfeeding, breastfeeding initiation
      and duration, personal characteristics, attitudinal and intrapersonal
      characteristics, hospital policies and intrapartum experience, sources of
      support, breastfeeding interventions, and review implications. DATA SYNTHESIS:
      Although the health benefits of breastfeeding are well documented and initiation
      rates have increased over the past 20 years, most mothers wean before the
      recommended 6-months postpartum because of perceived difficulties with
      breastfeeding rather than due to maternal choice. Women least likely to
      breastfeed are those who are young, have a low income, belong to an ethnic
      minority, are unsupported, are employed full-time, decided to breastfeed during
      or late in pregnancy, have negative attitudes toward breastfeeding, and have low
      confidence in their ability to breastfeed. Support from the mother's partner or a
      nonprofessional greatly increases the likelihood of positive breastfeeding
      behaviors. Health care professionals can be a negative source of support if their
      lack of knowledge results in inaccurate or inconsistent advice. Furthermore, a
      number of hospital routines are potentially detrimental to breastfeeding.
      Although professional interventions that enhance the usual care mothers receive
      increase breastfeeding duration to 2 months, these supportive strategies have
      limited long-term effects. Peer support interventions also promote positive
      breastfeeding behaviors and should be considered. CONCLUSIONS: A promising
      intervention is the complementation of professional services with peer support
      from a mother experienced in breastfeeding. This lay support appears to be an
      effective intervention with socially disadvantaged women.

PMID- 11843017
TI  - Embracing global similarities: a framework for cross-cultural obstetric care.
AB  - In this era of consistent global migration, cultural competency is necessary in
      all aspects of the care nurses provide to families. Cultural competency is
      particularly significant in maternal-newborn nursing because childbirth, as one
      of life's most significant events, is culturally shaped and socially constructed.
      In this article, a framework is provided to enable nurses to focus on several
      global phenomena and thus provide care that is more culturally sensitive,
      congruent with the client's needs, and competent. Suggestions for integrating
      cultural issues into nursing curricula are offered.

PMID- 11843018
TI  - Smoke free families: a tobacco control program for pregnant women and their
      families.
AB  - Tobacco use during pregnancy continues to cause health problems for women and
      children. Nurses can facilitate smoking cessation during pregnancy through the
      use of tobacco control guidelines and counseling tailored to pregnant women. In
      this article, the Treating Tobacco Use and Dependence: Clinical Practice
      Guideline is reviewed; the Smoke Free Families program, which is tailored for
      pregnancy, stage matched, and includes second-hand smoke control assistance, is
      described; and two models for integrating smoking cessation counseling into
      prenatal services are offered.

PMID- 11843019
TI  - Labor support: nurses' self-efficacy and views about factors influencing
      implementation.
AB  - OBJECTIVE: To develop and evaluate a questionnaire assessing nurses' self
      efficacy for labor support and to describe nurses' perceptions of factors
      assisting and preventing the provision of labor support. DESIGN: Two surveys
      completed by participants. SETTING: Five Canadian hospitals. PARTICIPANTS: For
      Phase 1, 81% (55/68) of maternity nurses at one hospital participated; for Phase
      2, 88% (152/173) of labor and delivery (L&D) nurses at four hospitals
      participated. MAIN OUTCOMES: Phase 1, psychometric properties of a new scale;
      Phase 2, nurses' self-efficacy for labor support and content analysis of nurses'
      comments. RESULTS: Phase 1: The Cronbach's alpha coefficient of the self-efficacy
      scale was .98, with a test-retest correlation of r(s) = .93. Higher (more
      positive) self-efficacy scores were found for L&D nurses compared with postpartum
      nurses, p < .0001. Phase 2: Mean self-efficacy scores for L&D nurses were high
      (range 86.9 to 92.1 out of 98). Written comments (n = 304) about the influencing
      factors in each work setting were coded into the following categories: staffing,
      physical environment, teamwork, management support, and negative staff attitudes.
      CONCLUSIONS: Phase 1 provided beginning evidence of the reliability and validity
      of the Self-Efficacy Labor Support Scale. Phase 2 found that L&D nurses' self
      efficacy or confidence to provide labor support was high. Therefore, it is
      recommended that future attention needs to be focused on factors related to the
      provision of labor support (staffing, physical environment, teamwork, management
      support, and negative staff attitudes). Attention to organizational factors is
      vital if nurses are the professional group to provide the evidence-based practice
      of continuous support for women in labor.

PMID- 11843020
TI  - Growth patterns of extremely low-birth-weight hospitalized preterm infants.
AB  - OBJECTIVE: To characterize the growth of extremely low-birth-weight (ELBW)
      infants during hospitalization in terms of weight gain, growth velocity, and
      relative change in weight. DESIGN: Retrospective, descriptive design. SETTING:
      Two neonatal intensive-care units located in the midwestern United States.
      PATIENTS: Thirty-five ELBW infants with a birth weight less than 1,000 g and
      appropriate for gestational age. MAIN OUTCOME MEASURES: Clinical data related to
      the infant's growth and nutrition were obtained from a chart review. Birth weight
      and discharge weight were compared following conversion of the weights to z
      scores. The discharge weight was compared to the median weight of a fetus of
      comparable gestational age based on an intrauterine growth reference. Growth
      velocity was determined (grams/day). RESULTS: Weight-for-age z scores decreased
      significantly between birth and discharge. By discharge, 89% of the infants had
      discharge weights less than the 10th percentile. The mean discharge weight was
      significantly less than the median weight of a fetus of comparable gestational
      age. Days to regain birth weight significantly affected growth outcomes.
      CONCLUSION: ELBW infants develop a growth deficit during the first few weeks of
      life that not only persists but also worsens during hospitalization. Potential
      causes of this growth deficit include the medical and nutritional management that
      are part of the usual care of ELBW infants. Because these infants are discharged
      with this growth deficit, catch-up growth will have to occur at home.

PMID- 11843021
TI  - Resolving the uncertainty of preterm symptoms: women's experiences with the onset
      of preterm labor.
AB  - OBJECTIVE: To describe expectant women's experiences with the onset of preterm
      labor. DESIGN: Qualitative, using grounded theory methods. SETTING: Southwestern
      tertiary women's hospital. PARTICIPANTS: Thirty pregnant women who were less than
      35 weeks gestation, had experienced preterm labor within the past 7 days, and had
      no previous experience with preterm labor. DATA SOURCE: Taped and transcribed
      interviews. RESULTS: Themes that emerged from the interview data included the
      following: recognition and naming of sensations, a consistent pattern of
      attribution of symptoms, the threat or risk inferred by the attributed cause of
      the symptom pattern, the associated certainty or uncertainty about these
      attributions, the process of interpreting and verifying symptom meaning, and the
      decision to self-manage the symptoms or engage health care assistance. The core
      process of women experiencing the onset of preterm labor symptoms was identified
      as "resolving the uncertainty of preterm labor symptoms: recognizing and
      responding to the possibilities." CONCLUSIONS: Preterm labor often is not within
      expectant women's consciousness. They may attribute the symptoms to
      nonthreatening causes, which results in delays in seeking care for preterm labor.
      Education about symptom patterns at the onset of preterm labor will increase the
      probability that women and their health care providers will recognize and
      interpret the early, subtle symptoms that herald the onset of preterm labor.
      Uncertainty in illness theory and attribution theory offer frameworks for
      understanding women's experiences with the onset of preterm labor.

PMID- 11843023
TI  - Cytomegalovirus infection: perinatal implications.
AB  - Cytomegalovirus (CMV), a member of the herpes virus family, is the most common
      cause of congenital infection in humans, affecting 0.5-3% of all newborns
      worldwide. Congenital cytomegalovirus infection is the leading infectious cause
      of deafness, learning disabilities, and mental retardation in children. The high
      prevalence of cytomegalovirus in the general population, unpredictability of
      transmission, and asymptomatic nature of the disease in otherwise healthy women
      challenge prevention and treatment efforts.

PMID- 11843022
TI  - The menopause experience: a woman's perspective.
AB  - OBJECTIVE: To understand the complexities of the experience of menopause in
      American women from diverse ethnic and socioeconomic backgrounds. The specific
      aims of this phenomenologic study were to (a) examine and interpret the reality
      of the menopausal transition as experienced by American women and (b) identify
      common elements and themes that occur as a result of the complexities of this
      experience. DESIGN: Data for this qualitative study were gathered through
      semistructured interviews with 15 women who experienced natural menopause.
      PARTICIPANTS: A multiethnic sample of 15 menopausal American women in
      Massachusetts was selected from a pool of voluntary participants from the Boston
      area. DATA ANALYSIS: The interviews were analyzed to identify themes pertinent to
      the personal experience of menopause. Those themes, extracted from the
      similarities and differences described, represent broad aspects of these women's
      experiences. RESULTS: Three major themes or phases were identified: expectations
      and realization, sorting things out, and a new life phase. Although some women
      expressed similar thoughts in particular categories, no two women had the same
      experience of menopause. CONCLUSIONS: The data support the premise that the
      experience of menopause in American women is unique to each individual and that
      the meaning or perspective differs among women. The data revealed the
      complexities of this human experience by explicating personal meanings related to
      experiences, expectations, attitudes, and beliefs about menopause.

PMID- 11843024
TI  - Chlamydia during pregnancy: implications and impact on perinatal and neonatal
      outcomes.
AB  - Chlamydia is the most prevalent sexually transmitted disease in the United
      States, with an estimated 3 million cases occurring annually. Untreated Chlamydia
      can cause severe, costly reproductive and other health problems with both short-
      and long-term consequences. When Chlamydia coexists with pregnancy, it can have
      negative consequences for the woman, the pregnancy, and the newborn. Nurses are
      in important positions to ensure safe health care practices for all pregnant
      women. Awareness of the perinatal implications and routine screening for
      Chlamydia in pregnant women will provide safer health care for the mother and her
      baby.

PMID- 11843025
TI  - Diagnosis and treatment of herpes simplex infection during pregnancy.
AB  - When pregnant women acquire primary herpes simplex genital infections or
      experience recurrent infections around the time of delivery, the risk of
      transmitting the disease to their newborns is significant. This perinatal
      transmission can result in a serious neonatal illness. Issues surrounding
      screening, treatment, and mode of delivery to prevent perinatal transmission
      often are confusing and controversial. Nurses delivering care to childbearing
      women and their newborns must be aware of the current information to give
      accurate and helpful information and support. Nurses also need to understand the
      effect this disease has both physiologically and psychosocially on women with
      primary infections, recurrent infections, and women at risk of acquiring the
      infection during pregnancy.

PMID- 11843026
TI  - Obstructive jaundice results in increased liver expression of uncoupling protein
      2 and intact skeletal muscle glucose metabolism in the rat.
AB  - BACKGROUND: A majority of patients with pancreatic cancer have obstructive
      jaundice and diabetes with skeletal muscle insulin resistance. Surgery for these
      patients is associated with significant morbidity. Uncoupling protein 2 (UCP2)
      has been proposed to regulate energy expenditure and promote liver vulnerability.
      The effects of obstructive jaundice on muscle glucose metabolism and expression
      of UCP2 in liver and muscle are unknown. METHODS: Rats were operated with bile
      duct ligation (BDL). After 7 days, UCP2 mRNA levels were determined in liver and
      muscle. Simultaneously, insulin-stimulated glucose transport and glycogen
      synthesis in skeletal muscle were analyzed in vitro. RESULTS: The jaundiced rats
      lost more weight than pair-fed controls. UCP2 mRNA levels were increased 5-fold
      in liver but not in muscle in jaundiced rats compared to pair-fed controls. The
      jaundiced rats were hypoglycemic and hypoinsulinemic but demonstrated intact or
      enhanced insulin action on skeletal muscle glucose transport and glycogen
      synthesis in vitro. Muscle glycogen content was increased in the jaundiced rats.
      CONCLUSIONS: Experimental obstructive jaundice in the rat is associated with
      increased liver expression of UCP2, rapid weight loss, and intact insulin action
      on skeletal muscle glucose metabolism. Obstructive jaundice, by upregulated liver
      UCP2, may contribute to the cachexia and high surgical morbidity observed in
      these patients, but not to skeletal muscle insulin resistance in pancreatic
      cancer patients.

PMID- 11843027
TI  - Identification of Helicobacter pylori DNA in human cholesterol gallstones.
AB  - BACKGROUND: The gallbladder mucosa secretes hydrogen ions and is covered by
      mucus. The environmental conditions for bacterial colonization are similar to
      those in the stomach. Gallbladder stones often contain DNA from enteric bacteria,
      but no compelling evidence demonstrates that Helicobacter spp. have been present.
      The aim of this study was to establish bacterial DNA profiles in cholesterol
      gallstones with special reference to Helicobacter pylori. METHODS: Cholesterol
      gallstones from 20 patients were subjected to polymerase chain reaction,
      bacterial profiling by temporal temperature gradient gel electrophoresis,
      automated DNA sequencing, and Southern blot analysis using a Helicobacter sp.
      specific primer. A nested ureI-PCR assay was used to discriminate between gastric
      and non-gastric H. pylori. RESULTS: TTGE, partial 16S rDNA sequencing, and
      hybridization analysis revealed the presence of DNA presumably representing a
      mixed bacterial flora in cholesterol gallstones, including H. pylori in the
      gallstone centres in 11 out of 20 patients. In three cases, the urel-PCR assay
      revealed non-gastric H. pylori. CONCLUSIONS: These data support the presence of
      DNA from a mixed bacterial population, including H. pylori in cholesterol
      gallstones, reflecting either that H. pylori is an indigenous part of a flora in
      the stone-containing gallbladder or, alternatively, that H. pylori colonization
      in the biliary tract predisposes to cholesterol gallstone formation.

PMID- 11843028
TI  - Post-infantile giant cell hepatitis associated with autoimmune hepatitis and
      polyarteritis nodosa.
AB  - We report the case of a patient with corticosteroid-responsive giant cell
      hepatitis associated with typical manifestations and changes of polyarteritis
      nodosa from the kidney and central nervous system. Initially, the patient
      presented with transient right hemiparesis, followed by spontaneous remission
      without any abnormalities on computed tomography scan, magnetic resonance imaging
      and cerebrospinal fluid examination. A few months later he was admitted to our
      clinic because of icterus, peripheral oedema and abdominal distension. He was
      found to have clinical signs of active cirrhosis. Serological tests for hepatitis
      B, C and HIV virus were negative. Serum ceruloplasmin. a1-AT and ferritin levels
      were within normal limits. Antinuclear antibodies were positive (1: 160). Liver
      biopsy showed micronodular cirrhosis with many eosinophils in the portal tracts
      and giant hepatocytes with multiple nucleoli in the lobule. Fulfilling the
      diagnostic criteria for autoimmune hepatitis, he was started on treatment with
      prednisolone and azathioprine, resulting in both clinical and biochemical
      responses. Four years later he presented with severe pain at the right
      costovertebral angle. Ultrasonography revealed a haematoma at the right kidney,
      and selective angiography of the abdominal aorta, renal arteries and hepatic
      artery documented microaneurysms in both kidney and liver arteries. Because of
      severe haemorrhage, right nephrectomy was performed. Histology of kidney specimen
      showed characteristic lesions of polyarteritis nodosa. Several months later,
      while on treatment with prednisolone and cyclophosphamide, the patient
      experienced a fatal episode of brain haemorrhage. An association between
      autoimmune hepatitis, polyarteritis nodosa and postinfantile giant cell hepatitis
      has not been reported previously.

PMID- 11843029
TI  - Effect of ethanol on spontaneous phasic contractions of cat gastric smooth
      muscle.
AB  - BACKGROUND: Ethanol is generally believed to inhibit extracellular Ca2+ influx,
      thereby inhibiting gastric muscle contraction. Recently, we observed that
      verapamil inhibited only the amplitude of spontaneous phasic contractions,
      whereas ethanol inhibited both amplitude and frequency. In our objective to
      investigate the mechanism of ethanol's inhibition of gastric motility, the
      involvement of various protein kinases in ethanol-inhibited spontaneous phasic
      contractions of the stomach muscle strips was tested. METHODS: Circular muscle
      strips (2.0 x 0.2 cm) were prepared from the corpus of cat stomach in order to
      measure isometric contraction in a chamber filled with Krebs-Ringer solution (pH
      7.4, temperature 36 degrees C) bubbled with 5% CO2 in O2. RESULTS: Spontaneous
      phasic contraction was not affected by various receptor antagonists (I microM
      atropine, 1 microM hexamethonium, 1 microM phentolamine and 1 microM propranolol)
      or 1 microM tetrodotoxin. EGTA and verapamil dose-dependently inhibited only the
      amplitude of spontaneous phasic contractions and not the frequency. Ethanol dose
      dependently inhibited both the amplitude and frequency of phasic contractions.
      The amplitude and frequency of spontaneous phasic contractions were significantly
      inhibited by protein kinase C and tyrosine kinase inhibitors. However, neither
      protein kinase C activator nor various phosphatase inhibitors blocked the
      inhibitory effect of ethanol. CONCLUSIONS: Ethanol appears to inhibit spontaneous
      phasic contractions by a mechanism other than the inhibition of protein kinase C
      or tyrosine kinase or the inhibition of extracellular Ca2+ influx.

PMID- 11843030
TI  - Analysis of the CTLA4 gene in Swedish coeliac disease patients.
AB  - BACKGROUND: A genetic susceptibility to coeliac disease is well established,
      involving HLA and non-HLA components. CTLA4 is an important regulator of T-cell
      function and some studies have suggested that sequence variation in the gene
      might be a determinant of disease susceptibility, although the evidence is
      conflicting. METHODS: Sixty-two children with biopsy-proven coeliac disease
      attending a single centre in Sweden were studied. All were genotyped for presence
      of the HLA-DQA1*0501, B 1*0201 alleles. Those who carried the HLA-DQ heterodimer
      (58/62) were genotyped for the +49 (A/G) exon I polymorphism. The transmission
      disequilibrium test (TDT) was used to test for association between coeliac
      disease and the A allele. The entire CTLA4 gene was screened for other sequence
      variants using a combination of conformation-sensitive gel electrophoresis and
      direct sequencing. RESULTS: A significant association between the exon I
      polymorphism and coeliac disease was observed (P = 0.02). No other sequence
      variants in CTLA4 were detected. CONCLUSIONS: This study provides further
      evidence that variation in CTLA4 is a determinant of coeliac disease
      susceptibility. If not mediated through the +49 (A/G) dimorphism directly, then
      the effect is likely to be mediated through linkage disequilibrium.

PMID- 11843031
TI  - Effect of calories and fat on postprandial gastro-oesophageal reflux.
AB  - BACKGROUND: Gastro-oesophageal reflux (GOR) is commonly considered to be worsened
      by fatty food, but it has recently been shown that changing the fat content of
      equicaloric meals has no effect on GOR over a 3-h postprandial period. Our aims
      were to verify this finding over a longer postprandial period and test the
      hypothesis that increasing the caloric content of balanced meals increases GOR.
      METHODS: Thirteen healthy subjects (6 men) aged 19-31 years underwent 6-h
      oesophageal pH monitoring after 3 solid/liquid meals of the same volume and
      osmolarity eaten on separate days in a randomized order: a) high fat (58% fat)
      2.8 MJ; b) balanced (23% fat) 2.8 MJ; and c) balanced low calorie (25% fat) 1.6
      MJ. RESULTS: The mean percentage of time at pH < 4 and the mean number of reflux
      episodes after the balanced 2.8 MJ meal (3.0% and 11.5. respectively) were higher
      (P < 0.05) than after the balanced 1.6 MJ meal (1.6% and 7.2) and similar to
      those after the equicaloric (2.8 MJ) high-fat meal (2.5% and 9.3). Acid clearance
      time was similar after all three meals. CONCLUSIONS: Our data suggest that advice
      on dietary habits in patients with GOR disease should be concentrated on
      decreasing the caloric load of meals rather than their fat content.

PMID- 11843032
TI  - Production of anti-endomysial antibodies in cultured duodenal mucosa: usefulness
      in coeliac disease diagnosis.
AB  - BACKGROUND: Although anti-endomysial antibodies (EmA) have been found in the
      supernatants of cultured intestinal mucosa from patients with coeliac disease
      (CD), in no study has the clinical reliability of this new diagnostic tool been
      investigated. Our aims were to evaluate the clinical usefulness of the in vitro
      production of EmA in CD diagnosis in consecutive patients with suspected CD, and
      to evaluate the reliability of the in vitro challenge in CD patients on a gluten
      free diet (GFD). METHODS: For the former aim, consecutive patients who were due
      to undergo intestinal biopsy for suspected diagnosis of CD were enrolled:
      according to the final diagnosis, these patients were divided into two groups:
      Group 1 comprised 91 newly diagnosed CD patients (40 males; age range 7 months to
      84 years), Group 2 included 100 subjects with diseases other than CD (44 males;
      age range 9 months to 76 years). For the latter aim, we also studied 21 CD
      patients on a gluten-free diet after 16-123 months (8 males; age range 3-51
      years), with normal intestinal architecture (Group 3) and 22 patients who served
      as controls (12 males; age range 4-60 years) with gastroesophageal reflux disease
      like symptoms (Group 4). All patients underwent determination of serum anti
      gliadin (AGA) and EmA antibodies, histology evaluation of the intestinal biopsies
      and EmA assay in the supernatants of in vitro gliadin-challenged duodenal mucosa.
      RESULTS: EmA assay in the supernatants showed a sensitivity and specificity of
      96% and 100%, respectively; these were not significantly different from those
      observed for serum EmA (88% and 99%, respectively). However, EmA assay in the
      supernatants was useful in CD patients with mild intestinal histology lesions
      (infiltrative/hyperplastic type): in this subgroup it was positive in 9/12 of
      cases, but serum EmA was positive in only 2/12. As regards the reliability of the
      in vitro gliadin challenge, EmA production in supernatants was recorded only in
      10/21 CD patients on a gluten-free diet. The patients with a positive in vitro
      challenge had a higher number of intra-epithelial lymphocytes than patients with
      a negative challenge. CONCLUSIONS: 1) EmA assay in the medium of cultured
      intestinal biopsy can detect gluten-sensitive enteropathy, characterized by an
      infiltrative/hyperplastic histological pattern, which is often associated with
      negative serum EmA. 2) The in vitro challenge in CD patients on a gluten-free
      diet detects EmA production in the culture medium only in half of the cases and
      other studies must be performed to evaluate whether EmA production after in vitro
      challenge can be considered a reliable test for confirming CD diagnosis.

PMID- 11843033
TI  - Living with coeliac disease: controlled study of the burden of illness.
AB  - BACKGROUND: Coeliac patients improve vastly when started on a gluten-free diet.
      After 10 years. however, women show a lower level of subjective health than men
      do. We investigated whether this could be explained by differences in the
      perceived disease burden. METHODS: We studied 68 coeliac patients (34 women)
      (mean age 57 years, range 32-75) and matched type-2 diabetes controls treated for
      a mean of 10 years. They were examined by a 9-item Burden of Illness (BI)
      protocol comprising perceived worries, restrictions and subjective outcome. The
      subjective health was assessed with the Short Form 36 Health Survey (SF-36)
      questionnaire. RESULTS: The importance of complying with the diet was ranked
      similarly high by male and female coeliac patients. However, women were less
      satisfied with the outcome at 10 years than men were, and expressed more concern
      about the impact on socializing with friends and having to abstain from important
      things in life. None of these aspects distinguished male and female diabetic
      patients. Coeliac women showed a higher BI sum score than men did, and this was
      inversely related to their SF-36 General health, Vitality and Mental Health
      scores. CONCLUSIONS: Coeliac women adhering to the treatment regimen for several
      years perceive the disease burden to be worse than men do. In the light of
      similar differences in their quality of life, inquiry is warranted into the way
      coeliac men and women are coping with the disorder.

PMID- 11843034
TI  - Electrogenic ion transport in duodenal biopsies from children with coeliac
      disease.
AB  - BACKGROUND: The aim of this work was to study whether different degrees of
      duodenal mucosal damage in coeliac disease (CD) influenced secretory responses to
      well-known secretagogues. METHODS: Intestinal biopsies from 53 patients in
      different clinical phases of CD and 34 patients without CD and with normal
      histology were studied in a modified Ussing chamber. The electrogenic responses
      with and without pretreatment with indomethacin-to prostaglandin E2,
      aminophylline, dibutyryl-cAMP and acetylcholine were followed by continuous
      measurements of potential difference (Pd). Tissue resistance and epithelial
      current (Im) were calculated. RESULTS: All secretagogues induced a similar
      pattern, with a greater increase in Pd and Im in biopsies with villous atrophy
      compared to controls. The electrophysiological response was correlated to the
      serum levels of IgA gliadin antibodies. The most prominent electrophysiological
      increase was found in the biopsies with partial atrophy. Indomethacin had a
      greater impact on the response to secretagogues in the more severely damaged
      mucosa. CONCLUSION: The electrogenic secretory response in the proximal small
      intestine was enhanced and related to serum levels of IgA gliadin antibodies and
      to the degree of mucosal damage in biopsies from children with active CD compared
      to controls.

PMID- 11843035
TI  - First-degree relatives are frequently affected in coeliac disease and dermatitis
      herpetiformis.
AB  - BACKGROUND: Coeliac disease and dermatitis herpetiformis are phenotypically
      distinct gluten-sensitive diseases. Coeliac disease is known to cluster in
      families, whereas there is little evidence for dermatitis herpetiformis and for
      the occurrence of both diseases in the same families. METHODS: The study group
      comprised 380 patients with coeliac disease and 281 patients with dermatitis
      herpetiformis, with a total of 3158 first-degree relatives, followed up for a
      mean of 14 years. The patients were questioned about affected first-degree
      relatives. The prevalence and incidence of biopsy-proven coeliac disease and
      dermatitis herpetiformis in relatives were determined. RESULTS: Seventy-three
      (19.2%) patients with coeliac disease and 51 (18.1%) with dermatitis
      herpetiformis had affected first-degree relatives. The prevalence among relatives
      was similar for both diseases; 4.7% and 3.9% of the relatives had coeliac disease
      and 0.8% and 1.5% had dermatitis herpetiformis, respectively. The disease
      prevalence was 7% among siblings, 4.5% among parents and 3.5% among children. The
      annual incidence was 3/1,000 relatives, which is 15 times higher than among the
      general population. Coeliac disease and dermatitis herpetiformis were mixed in
      several multiple-case families. CONCLUSIONS: The present long-term follow-up
      study of coeliac disease and dermatitis herpetiformis shows that every fifth
      patient can have affected first-degree relatives, and that the prevalence among
      relatives is 5.5%. Dermatitis herpetiformis segregates also in the families of
      patients with coeliac disease, and vice versa, indicating the same genetic
      background.

PMID- 11843036
TI  - Not all HLA DR3 DQ2 haplotypes confer equal susceptibility to coeliac disease:
      transmission analysis in families.
AB  - BACKGROUND: HLA-DQ is the only established susceptibility factor for coeliac
      disease. We tested whether all HLA haplotypes with the known risk marker, HLA
      DQ2, confer equal susceptibility to coeliac disease, i.e. whether haplotype
      transmission from DQ2 homozygous parents to patients is random. The random
      transmission would strengthen the importance of DQ2 as the only risk factor
      within the HLA region. METHODS: Inheritance of DQ2-positive haplotypes from
      parent to patients was investigated in 14 of 127 Finnish coeliac families who had
      an HLA-DQ2 homozygous parent. HLA alleles and 18 HLA-linked microsatellite
      markers were used to determine the haplotypes, which were divided into those
      transmitted and those non-transmitted from DQ2-homozygous parents to patients:
      RESULTS: Transmitted haplotypes differed clearly from those not transmitted. The
      alleles in the transmitted haplotypes were strongly conserved and predominantly
      consisted of the well-known HLA-A*01, B*08, DRB1*03, DQ2, DPB1*0101 haplotype.
      The non-transmitted haplotypes, on the other hand, were significantly more
      heterogeneous; in particular, markers near HLA-A and -B genes differed from the
      transmitted haplotypes. CONCLUSIONS: The results suggest that DQ2 is not the only
      HLA-linked genetic risk factor for coeliac disease but the conserved haplotype
      harbours at least one other risk gene.

PMID- 11843037
TI  - Reliability of 24-hour oesophageal pH monitoring under standardized conditions.
AB  - BACKGROUND: Twenty-four-hour pH monitoring is an investigation technique that can
      give both false-positive and false-negative results, depending on patient factors
      such as diet and different activities. The aim was to study the reproducibility
      of 24-h oesophageal pH monitoring under as standardized conditions as possible in
      patients with symptoms of gastro-oesophageal reflux disease. METHODS: Antimony pH
      electrodes were used in 22 adult patients who were investigated twice, 6 weeks
      apart, under identical conditions. They were hospitalized and were served a
      standardized diet which had been tested to contain no lower than pH 5.0. Neither
      coffee nor smoking was allowed. The patients had to refrain from proton-pump
      inhibitors for 10 days and H2 blockers for 2 days prior to the investigation. The
      paired t test was used. RESULTS: There was no significant difference in total
      reflux time, upright or supine reflux time, or longest reflux periods between the
      two test occasions. However, there were discordant results in six patients who
      had normal total reflux time on one test occasion but pathological results on the
      other. CONCLUSION: Since the biological variability of gastro-oesophageal reflux
      is not negligible from time to time, a normal 24-h oesophageal pH test should be
      assessed with caution.

PMID- 11843039
TI  - Surgery for Crohn colitis over a twenty-eight-year period: fewer stomas and the
      replacement of total colectomy by segmental resection.
AB  - BACKGROUND: This study describes how surgery for Crohn colitis developed between
      1970 and 1997, towards the end of which period limited resection and medical
      maintenance treatment was introduced. METHODS: A cohort of 211 patients with
      Crohn colitis (115 population-based), of which 84 had a primary colonic resection
      (42 population-based), was investigated regarding indication for surgery, the
      time from diagnosis to operation, type of primary colonic resection, risk for
      permanent stoma and medication over four 7-year periods. RESULTS: Comparison of
      the periods 1970-90 and 1991-97 revealed that active disease as an indication for
      surgery decreased from 64% to 25% (P<0.01) while stricture as an indication
      increased from 9% to 50% (P < 0.001). Median time from diagnosis to operation
      increased from 3.5 to 11.5 years (P < 0.01). Proctocolectomy or colectomy fell
      from 68.8% to 10% of the primary resections, whereas segmental resection
      increased from 31.2% to 90%. At the end of the first 7-year period, 26% had
      medical maintenance treatment, steroids or azathioprine taken by 7%.
      Corresponding figures for the last period were 70% and 49%. Patients diagnosed
      during the last two time-periods had less risk for surgery (P = 0.017), permanent
      stoma (P < 0.01) and total colectomy (P < 0.01). Findings were similar in the
      population-based cohort. CONCLUSIONS: Current management of Crohn colitis implies
      a longer period between diagnosis and surgery, a reduced risk for surgery and
      permanent stoma, and the replacement of total colectomy by segmental resection.

PMID- 11843038
TI  - Hyperhomocysteinaemia, coagulation pathway activation and thrombophilia in
      patients with inflammatory bowel disease.
AB  - BACKGROUND: The 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C-->T
      polymorphism encoding the thermolabile variant is, when present as homozygote
      type (TT variant), a known genetic cause of mild hyperhomocysteinaemia (HHCY).
      This polymorphism has been observed in increased numbers in patients with
      inflammatory bowel disease (IBD). Coagulation and fibrinolysis are activated in
      patients with active IBD, but it is not known whether raised plasma homocysteine
      (HCY) found in patients with IBD significantly contributes to this activation.
      The aim of this study was to investigate if HHCY or presence of the TT variant
      significantly induces a hypercoagulable state in IBD patients receiving anti
      inflammatory therapy during active disease, and to study if genetic determinants
      for thromboembolic disease are more frequent in these patients. METHODS: The
      study was designed as a cross-sectional study in an outpatient clinic comprising
      106 IBD patients receiving anti-inflammatory therapy. Markers of coagulation were
      measured in order to elucidate whether patients with HHCY or the MTHFR TT variant
      were hypercoagulant compared with patients with no impairment of HCY metabolism.
      In addition, markers of inflammation and acute-phase reactants were measured in
      order to compare activity during active disease and during remission. Genetic
      determinants of thromboembolic disease in patients with IBD and in relevant
      controls were investigated in the expectation of a more frequent occurrence of
      these markers of thrombophilia if hypercoagulability could be a primary or
      contributory factor in IBD. RESULTS: No significant difference could be found in
      coagulation activity, acute-phase reactants or inflammatory markers in IBD
      patients with the TT variant of the 677C-->4T polymorphism or high (>15
      micromol/L) plasma HCY levels, compared with IBD patients with no impairment of
      HCY metabolism. In patients with IBD, the coagulation activity was significantly
      increased during active disease compared with a state of remission. As expected,
      a significant difference regarding interleukin 6, C-reactive protein and
      erythrocyte sedimentation rate was present in IBD, comparing active disease with
      a state of remission. No significant complement activation was present in either
      of the groups or during active disease. Neither of the allele frequencies of
      genetic determinants for thrombophilia (coagulation factor V 1691G-->A (factor V
      Leiden) and factor II 20210G-->A polymorphisms) in the background population
      differed significantly from that in IBD patients. CONCLUSIONS: This study found
      no correlation between the MTHFR TT variant or HHCY and a hypercoagulable state
      in IBD patients receiving anti-inflammatory treatment. This coagulation activity
      is high during exacerbations of disease, but a considerable reduction is seen in
      patients on anti-inflammatory therapy compared with non-treated patients.
      Coagulation activation in IBD is probably a consequence of the inflammatory
      nature of the disease. That thrombophilia could be a contributory or primary
      factor in the development of IBD is not supported by the present study, as the
      frequencies for the genetic determinants for thrombophilia are similar in IBD
      patients and controls.

PMID- 11843040
TI  - Phenol toxicity and conjugation in human colonic epithelial cells.
AB  - BACKGROUND: Colonic epithelial cells are exposed to a range of potentially
      harmful luminal factors. including phenols, but it is unresolved whether these
      compounds impair the integrity of the epithelium. The aim of this study was to
      describe the effect of phenol exposure on human colonic epithelial cells in vitro
      and the conjugation pathways involved in detoxification. METHODS: Primary human
      colonic epithelial cell cultures or HT-29 cell cultures were exposed to
      paracetamol, dinitrophenol or phenol (0.1-5 mM) for 24 h. Cell viability was
      measured using the methyltetrazoleum test. Phenol conjugation products released
      from cell cultures were identified by high-pressure liquid chromatography. Phenol
      glucuronidase (PGD) and sulphotransferase (PST) enzyme activities were measured
      in isolated cell homogenates. RESULTS: Paracetamol, dinitrophenol and phenol
      (>1.25 mM) significantly impaired the viability of primary colonic epithelial
      cell cultures. No differences between cell cultures from ulcerative colitis and
      control patients were observed. Paracetamol (5 mM) also induced significant cell
      damage in HT-29 cells. Glucuronidation was the preferred conjugation pathway in
      both cell models, despite the presence of PGD and PST activity. CONCLUSION:
      Phenols have a direct toxic effect on human colonic epithelial cells in vitro,
      which supports the view that dietary fermentation metabolites may be involved in
      the modulation of chronic bowel inflammation.

PMID- 11843041
TI  - Does intake of alcohol increase the risk of presence and growth of colorectal
      adenomas followed-up in situ for three years?
AB  - BACKGROUND: Alcohol has been suggested as a promoter in the development of
      colorectal cancer (CRC). Our aim was to examine if alcohol intake was related to
      the presence and growth of colorectal adenomas <9 mm followed up in situ for 3
      years. METHODS: We compared 87 adenoma cases to 35 'hospital' and 35 healthy
      controls (age- and sex-matched and proven to be polyp-free). These cases were
      participating in a 3-year intervention study against growth and recurrence of
      polyps. Alcohol data were obtained using a structured interview (I) and a 5-day
      dietary record by weighing (DR). RESULTS: The median intakes of alcohol were 5
      g/day (I) and 6 g/day (DR). Increasing differences were found between I and DR
      with increasing alcohol intake. Increasing total alcohol intake showed a tendency
      to an inverse association with adenoma occurrence (ORs <0.5), in contrast to the
      tendency of a positive association with adenoma growth (ORs >5.8). No significant
      beverage-specific effects were observed at this low alcohol intake level. Those
      with an intake of >20 g alcohol/day (18%) had several indicators of an
      'unhealthy' lifestyle that may also be independently associated with adenomas,
      and even CRC. CONCLUSION: A very low intake of alcohol (<5 g/day) did not
      increase the risk of presence and of growth of adenomas followed-up in situ for 3
      years, but we cannot exclude that an increased intake may increase the risk of
      adenoma growth.

PMID- 11843042
TI  - Demonstration of a direct stimulatory effect of bile salts on rat colonic
      epithelial cell proliferation.
AB  - BACKGROUND: Despite the clear demonstration that an increase in faecal bile salt
      concentration can augment colonocyte proliferation, it is still controversial
      whether bile salts act on these cells as direct mitogens or by inducing a damage
      related proliferative response. The goal of this study was to define the
      mechanism mediating the proliferative effect of bile salts on rat colonocytes.
      METHODS: Faecal bile salt concentration was increased by feeding rats on diets
      enriched with either bile salts or fats. Colonic mucosa proliferating cell
      nuclear antigen (PCNA) expression, histology and apoptosis, and faecal water
      cytolytic activity were evaluated to assess proliferation and direct or indirect
      signs of mucosal damage. RESULTS: Compared to standard diet, chenodeoxycholate-,
      deoxycholate- and fat-enriched diets produced a significant increase in both
      faecal water total bile salt concentration (46.0 versus 124.1, 145.9 and 498.5
      micromol/L, respectively) and percentage of PCNA-positive nuclei (30.5, versus
      37.7, 33.9 and 47.1, respectively) that appeared significantly correlated (r =
      0.8; P < 0.001). Chenodeoxycholate and deoxycholate fed animals showed colonic
      mucosa histology and faecal water cytolytic activity similar to controls, with a
      significantly reduced apoptotic index. Rats fed on high fat diet, however, showed
      a mild inflammatory infiltrate associated with an increased apoptosis and faecal
      water cytolytic activity, all conditions not apparently determined by the
      increased faecal water total bile salt concentration. CONCLUSIONS: The results
      obtained in this study demonstrate that bile salts act as direct mitogens on
      colonic epithelial cells.

PMID- 11843043
TI  - Increased gastric acid secretion in cholecystokinin-1 receptor-deficient Otsuka
      Long-Evans Tokushima fatty rats.
AB  - BACKGROUND: It is hypothesized that cholecystokinin stimulates acid secretion
      directly and indirectly by binding to CCK-2 (CCK-B/gastrin) receptors on both
      parietal and enterochromaffin-like cells. At the same time, however, it inhibits
      acid responses by stimulating the paracrine secretion of somatostatin from D
      cells and thereby exerts a tonic inhibition on the parietal cells. To test the
      validity of this hypothesis, we determined gastric acid secretion in the CCK-1
      (CCK-A) receptor-deficient Otsuka Long-Evans Tokushima fatty (OLETF) rats.
      METHODS: Gastric acid secretion was determined in the acute fistula OLETF and the
      control Long-Evans Tokushima Otsuka (LETO) rats. Plasma concentrations of
      gastrin, CCK, somatostatin and histamine were determined by radioimmunoassay. The
      levels of CCK-2 receptor mRNA in the mucosa of the glandular stomach were
      determined by Northern blot analysis. RESULTS: Pentagastrin- and CCK-8-stimulated
      as well as basal acid outputs in OLETF rats were significantly higher than those
      in LETO rats. CCK-2 receptor antagonist reduced basal acid outputs and completely
      suppressed CCK-8-stimulated acid secretion in both strains. CCK-8 enhanced the
      pentagastrin-stimulated gastric acid output in OLETF rats, but not in LETO rats.
      In LETO rats, CCK-1 receptor antagonist increased CCK-8-stimulated gastric acid
      secretions to those in OLETF rats. The level of CCK-2 receptor mRNA in the
      stomach in OLETF rats was 2-fold higher than that in LETO rats. In OLETF rats,
      plasma concentrations of CCK and histamine were higher, whereas somatostatin
      concentrations were lower than those in LETO rats, with no change in basal plasma
      gastrin concentrations. CONCLUSIONS: These results in the CCK-1 receptor
      deficient OLETF rats confirmed that CCK stimulates acid secretion by binding to
      CCK-2 receptors, but at the same time inhibits acid responses by stimulating the
      paracrine secretion of somatostatin from D cells in the gastric mucosa.

PMID- 11843044
TI  - Upper gastrointestinal cancer in a population-based screening program with fecal
      occult blood test for colorectal cancer.
AB  - BACKGROUND: Screening with Hemoccult-II (H-II) followed by colonoscopy, when
      fecal occult blood is demonstrated, reduces mortality from colorectal cancer.
      Whether upper gastrointestinal investigation is necessary when colonoscopy does
      not reveal any significant colorectal lesion is doubtful, and is the subject of
      this study. MATERIAL: In 1985, 30,967 persons from the general population
      register of Funen were randomized to biennial H-II screening. A positive test was
      followed by colonoscopy and no attempt was made to evaluate the upper
      gastrointestinal tract. Based on the information from the Funen Patient Database,
      the National Board of Health's Register of Death Causes, the Cancer Register and
      the National Register of Patients, all persons with malignancy of the
      gastrointestinal tract were identified. RESULTS: During 15 years and 8 screening
      rounds, 1,767 tests were positive; 1,536 complete colonic investigations detected
      colorectal cancer in 182 persons, adenoma > or = 10 mm in 440 persons, and in 879
      investigations no colorectal lesion was found. Upper GI cancers were diagnosed in
      209 persons within 2 years of the H-II test (199 after a negative H-II and no
      more than 10 persons within 2 years of a positive test). Among the 10, two were
      diagnosed as a consequence of symptoms at the time of screening. CONCLUSION: It
      is unjustified to perform upper gastrointestinal investigation in asymptomatic
      persons with a positive H-II in a Danish population screening for colorectal
      cancer.

PMID- 11843045
TI  - Aminosalicylates: potential antineoplastic actions in colon cancer prevention.

PMID- 11843046
TI  - Laparoscopic antireflux surgery in routine hospital care.
AB  - BACKGROUND: The frequency of antireflux surgery has tripled since laparoscopic
      techniques were introduced. In Sweden, laparoscopic antireflux surgery is often
      done at local hospitals with a very low annual number of patients. Many surgeons.
      who may have limited experience with conventional antireflux surgery, have
      started to perform laparoscopic antireflux procedures, in spite of the well-known
      fact that there is a long learning curve for laparoscopic antireflux surgery.
      METHODS: A random sample of 225 of 660 patients operated on at high-volume and
      all 220 patients from low-volume hospitals were identified through a nation-wide
      register. Outcome 4 years after laparoscopic antireflux surgery was studied using
      a disease-specific questionnaire. RESULTS: Treatment failures were more common in
      the high-volume group than among patients operated on at low-volume hospitals,
      29.0% and 19.7%, respectively. In the high volume group, medication (specifically
      to relieve heartburn or acid regurgitation) was taken at least once a week and
      revisional surgery was found in 19.5% and 6.0%, respectively. Corresponding
      results in the low-volume group were 11.1% and 2.9%, respectively. None of these
      differences was statistically significant at the overall 0.05 level. CONCLUSION:
      A failure rate of almost 30% at 4 years' follow-up for patients operated on at
      relatively high-volume hospitals was disappointing, despite the fact that these
      results are population-based. Hospitals are encouraged to provide accounts of
      their results in an effort to identify the reasons for treatment failures, and
      for the public to have access to more objective information on different
      therapeutic options.

PMID- 11843047
TI  - Comorbidity of aerophagia in GERD patients: outcome of laparoscopic antireflux
      surgery.
AB  - BACKGROUND: While there is evidence that physiological data correlate poorly with
      quality-of-life data or patient-perceived symptom severity, most outcome studies
      of antireflux surgery still refer physiologic criteria. The aim of this
      prospective study was to establish whether concomitant aerophagia in GERD
      (gastroesophageal reflux disease) patients might influence the surgical outcome
      of laparoscopic 'floppy' Nissen fundoplication. METHODS: A total of 112 patients
      were divided into 2 subgroups: group 1 comprising GERD patients without
      aerophagia (n = 94; 84%); group 2 of GERD patients with concomitant aerophagia (n
      = 28; 16%). In all patients, requirements for surgery included an evaluation of
      symptoms (list of 17 symptoms; patients' grading from no--mild to moderate-
      severe), quality of life (Gastrointestinal Quality of Life Index: GIQLI),
      esophagogastroduodenoscopy, esophageal manometry and 24-h pH monitoring.
      Additionally, we asked for any potential stress relations to GERD symptoms.
      Surgical outcome was assessed 3 months and 1 year postoperatively. RESULTS: In
      group 2 patients before surgery, we found a significantly higher percentage with
      a mild impairment of esophageal motility, with a subjectively and objectively
      dominant reflux in the upright position, with a lower grading of esophagitis or
      Barrett esophagus, and with a stronger belief that stress was in any relation to
      perceived symptoms compared with group 1 patients. Additionally, these patients
      perceived typical and untypical symptoms more intensively. Factors such as
      DeMeester score and lower esophageal sphincter pressure did not differ
      preoperatively, the same as after antireflux surgery. Both groups profit
      significantly from surgery-a continuous reduction of symptom severity and quality
      of-life improvement was found. Group 1 patients showed an improvement in mean
      GIQLI from 93.4+/-8.3 points preoperatively to 123.1+/-7.3 and 122.9+/-9.0 points
      3 months and 1 year postoperatively, whereas group 2 patients demonstrated a
      lower outcome, from 82.2+/-9.1 points to 112.4+/-8.1 and 116.8+/-7.9 points
      postoperatively. This lesser improvement is the result of preoperative symptoms
      such as belching, bloating or flatulence, which many patients had after surgery.
      In addition, some of the group 2 patients suffered from subjective mild to
      moderate heartburn or dysphagia, but without any objective correlation.
      CONCLUSION: GERD patients with concomitant aerophagia demonstrated less
      symptomatic relief than patients without aerophagia. Moreover, patients with
      aerophagia showed less quality-of-life improvement after laparoscopic antireflux
      surgery. There were no significant differences in physiological outcome data
      between groups. Surgery in GERD patients with symptoms relating to aerophagia
      should be approached with great care. An additional psychological intervention in
      these patients might improve surgical outcome.

PMID- 11843048
TI  - Does Helicobacter pylori eradication reduce the long-term requirements for acid
      suppressants in patients with a history of peptic ulcer disease in general
      practice? Results from a four-year longitudinal study.
AB  - BACKGROUND: Acid suppressants, especially proton-pump inhibitors, are major
      contributors to the drug costs in primary care. Although Helicobacter pylori
      eradication reduces peptic ulcer relapse, some studies suggest that patients may
      remain symptomatic and continue to require acid-suppressant therapy. METHODS: We
      identified all patients taking long-term acid suppressants in a large primary
      health care clinic to determine the proportion who had peptic ulcer disease and
      to examine the effect of H. pylori eradication on their long-term requirement for
      acid suppressants. RESULTS: 126/394 patients taking long-term acid suppressants
      had a definite diagnosis of peptic ulcer. Of these 126 patients, 60 were
      considered appropriate for the study. At Stage 1 (May 1994), all patients were
      tested for H. pylori infection and positive patients (60/66) received eradication
      therapy with omeprazole 20 mg bd and amoxycillin (1 gm bd) or clarithromycin (500
      mg tds) for 2 weeks. Six weeks later (Stage 2) patients, requirements for
      continued acid-suppressant treatment were determined and previously positive
      subjects retested using the 13C urea breath rest. This showed that 70% (42/60)
      had been successfully eradicated. One year later (Stage 3), 44% (18/41) of the
      patients successfully eradicated still required acid suppressants. The majority
      of these patients (11/18; 61%) continued to remain on acid-suppressant treatment
      at 4 years (Stage 4) (95% CI 38%, 83%). CONCLUSIONS: We found that about 1/3 of
      all patients on long-term acid-suppressant therapy in General Practice had a
      confirmed diagnosis of peptic ulcer disease. Despite successful eradication
      treatment for H. pylori at the start of the study, about half of these patients
      still used acid suppressants after 1 year and 1/4 patients (11/41) in this group
      continued to remain on acid-suppressant treatment for another 3 years.

PMID- 11843050
TI  - Involvement of tumor necrosis factor alpha in intestinal epithelial cell
      proliferation following Paneth cell destruction.
AB  - BACKGROUND: An intravenous injection of diphenylthiocarbazone (dithizone), a zinc
      chelator, induces selective killing of Paneth cells which have a large amount of
      zinc in their cytoplasmic granules. A transient wave of intestinal epithelial
      cell proliferation occurs at 12 h after the injection. Paneth cells have tumor
      necrosis factor (TNF)-alpha protein in their cytoplasmic granules, and TNF-alpha
      has a proliferative effect on intestinal epithelial cells in vitro. The aim of
      this study is to clarify the in vivo role of TNF-alpha in intestinal epithelial
      cell proliferation using a dithizone-treated rat model. METHODS: Male Wistar rats
      received a dithizone (100 mg/kg of body weight) injection with or without TNF
      alpha inhibitor, pentoxifylline (100 mg/kg), neutralizing anti-TNF-alpha antibody
      (2 mg/kg), or nuclear transcription factor kappaB (NF-kappaB) inhibitors:
      pyrrolidine dithiocarbamate (100 mg/kg) or N-acetyl-L-cystein (100 mg/kg). The
      activation of NF-kappaB was examined by the electrophoretic mobility shift assay,
      and cellular proliferation by BrdU labeling. RESULTS: Without any inhibitors,
      dithizone treatment evoked NF-kappaB activation in the ileal mucosa with its peak
      level at 2 h after the injection. TNF-alpha inhibition reduced the NF-kappaB
      activation, and blocked a transient wave of epithelial cell proliferation 12 h
      after the injection. NF-kappaB inhibitors also reduced the NF-kappaB activation
      and epithelial cell proliferation. CONCLUSIONS: TNF-alpha released from
      degenerated Paneth cells was, in part, responsible for the intestinal cell
      proliferation through the activation of NF-kappaB, suggesting its proliferative
      effect on intestinal epithelial cells.

PMID- 11843049
TI  - Weak response of helicobacter pylori antibody is high risk for gastric cancer: a
      cross-sectional study of 10,234 endoscoped Japanese.
AB  - BACKGROUND: A large number of endoscoped members of the general Japanese
      population were surveyed to investigate the relationship between Helicobacter
      pylori infection and gastric cancer. Special attention was given to antibody
      titer and age of the subjects. METHODS: We performed gastrointestinal endoscopy
      and measured serum anti-H. pylori antibody in 10,234 consecutive Japanese who
      participated in a health examination program. Gastric cancer, when suspected, was
      confirmed by histology. We graded the H. pylori antibody titer into three groups
      in accordance with optical density values by ELISA: 'strongly positive', 'weakly
      positive', and 'negative'. RESULTS: Among the 10,234 subjects (men/women,
      7.021/3,213; mean age, 49.1 years), 4,909 (48%) were strongly positive, 1,750
      (17%) were weakly positive, and 3,575 (35%) were negative for H. pylori antibody.
      Thirty-seven cases of gastric cancer were found among the 10,234 subjects
      (0.36%); 23/4,909 (0.47%) in the strongly positive group, 9/1,750 (0.51%) in the
      weakly positive group, and 5/3,575 (0.14%) in the negative group. Both the
      strongly and weakly positive groups showed a higher risk of gastric cancer than
      the negative group. In the subjects over age 60, the weakly positive group seemed
      to show the highest risk for gastric cancer. CONCLUSIONS: In this investigation
      of 10,234 Japanese, based on endoscopy results, those with serum H. pylori
      antibody had an increased risk for gastric cancer, while those 'weakly positive'
      showed a high risk, particularly in the elderly.

PMID- 11843051
TI  - Coeliac disease among healthy members of multiple case coeliac disease families.
AB  - BACKGROUND: The main objective of the study was to assess the frequency of
      undetected coeliac disease among the first-degree relatives of families with two
      or more previously diagnosed coeliac disease patients. The value of the serum
      endomysial antibody test as a single means of detecting clinically silent coeliac
      disease was evaluated. The correlation of endomysial and tissue transglutaminase
      antibodies and the correlation of endomysial antibodies to the HLA typical for
      coeliac disease was determined. METHODS: A total of 137 multiple-case coeliac
      disease families with 872 family members were recruited; 466 healthy family
      members were simultaneously screened for gliadin and endomysial antibodies and
      thereafter for tissue tranglutaminase antibodies. Antibody-positive persons were
      typed for HLA-DQ2 and DQ8. The diagnosis of coeliac disease was based on the
      typical mucosal lesion on small-bowel biopsies. RESULTS: Forty-four (9.4%) of the
      healthy family members were positive for endomysial and 48 (10.3%) for gliadin
      antibodies; 42 biopsies revealed 29 new coeliac disease patients (6.2% of healthy
      individuals). Endomysial antibodies detected 97% and gliadin antibodies 52% of
      the new cases. All 44 endomysial-antibody-positive and 35 of 48 gliadin-antibody
      positive individuals were positive for DQ2. Tissue transglutaminase antibodies
      corresponded well with endomysial antibodies. CONCLUSIONS: Undetected coeliac
      disease is common even among healthy first-degree relatives of multiple case
      families. The findings emphasize the value of serum endomysial antibodies in the
      detection of clinically silent coeliac disease. Endomysial-antibody-positive
      individuals, unlike gliadin-antibody-positive ones, share the coeliac disease
      type HLA-DQ.

PMID- 11843052
TI  - A role for autoantibodies in some cases of acquired non-paraneoplastic gut
      dysmotility.
AB  - BACKGROUND: Antibody-mediated autoimmunity underlies a diverse range of
      disorders, particularly in the nervous system where domains of ion channels and
      receptors are potential targets. The aetiology of many adult-onset conditions of
      severe gut dysmotility is not known. We looked for antibodies to neuronal
      antigens in patients with severe (slow-transit-type) constipation (STC). METHODS:
      Eleven sera from adult-onset STC patients and 18 from childhood onset cases were
      tested by routine immunoprecipitation assays for antibodies against neuronal
      antigens including voltage-gated potassium channels (VGKCs), calcium channels
      (VGCCs), both muscle and neuronal acetylcholine receptor and glutamic acid
      decarboxylase (GAD). Results were compared with positive and negative control
      populations. RESULTS: Two of the 11 sera from patients with adult-onset STC
      showed highly positive anti-VGKC antibodies. Both had onset of symptoms de novo
      in adulthood without evidence of autoimmune, neoplastic or neurological disease.
      One of these patients, and one other, had anti-GAD antibodies. None of the
      childhood-onset STC had evidence of anti-neuronal antibodies. CONCLUSIONS: Anti
      neuronal antibodies are found in some patients with a condition of severe
      acquired gut dysmotility of previously unknown aetiology. Future studies may
      demonstrate an autoimmune role for such antibodies.

PMID- 11843054
TI  - Clinical and colonoscopic investigation of skipped periappendiceal lesions in
      ulcerative colitis.
AB  - BACKGROUND: Ulcerative colitis (UC) is typically a continuous and diffuse
      inflammation extending proximally from the rectum. However, skipped lesion in the
      appendiceal region has been reported recently. Although appendectomy has been
      shown to reduce the risk of UC, the clinical significance of skipped
      periappendiceal lesion remains unclear. The present study examined the
      relationship between the continuous distal lesion of UC and the skipped
      periappendiceal lesion by observing colonoscopic changes in both lesions.
      METHODS: Among 279 patients with UC who underwent total colonoscopy from January
      1994 to December 2000, 54 patients (19.4%) had skipped periappendiceal lesions.
      Serial colonoscopic examinations were performed in 35 of the 54 patients to
      determine the activities in the distal UC lesion and skipped periappendiceal
      lesion during the course of disease. RESULTS: Patients with skipped
      periappendiceal lesions were younger and had a longer history of UC than those
      without them, but no differences in sex ratio and treatment modality were
      observed between the two groups. In 28 of 35 patients (80%), the activity in the
      distal lesion correlated well with that in the skipped periappendiceal lesion.
      Both lesions were improved in 17 patients, unchanged in 5 patients and worsened
      in 6 patients. Linear regression analysis showed a significant correlation
      between the changes in colonoscopic activity index in the two lesions.
      CONCLUSION: A close association is found between disease activity in the skipped
      periappendiceal lesion and that in the distal lesion of UC.

PMID- 11843053
TI  - Risk of osteopenia after proctocolectomy and ileal pouch-anal anastomosis for
      ulcerative colitis.
AB  - BACKGROUND: The aim of our study was to evaluate the influence of pouchitis and
      villous atrophy on bone mineral density and metabolism at least 5 years after
      ileal pouch-anal anastomosis for ulcerative colitis (UC). METHODS: Eighty-eight
      subjects with a J-pouch operated on between 1985 and 1994, and 20 ulcerative
      colitis subjects with a conventional ileostomy were enrolled. Endoscopy was
      performed and spine and femoral neck bone mineral densities measured. Bone
      metabolism was assessed by measurement of serum levels of parathyroid hormone,
      osteocalcin, 25-hydroxyvitamin D3, calcium, alkaline phosphatase and urinary N
      telopeptide cross-linked of type I collagen (NTX). RESULTS: In the lumbar spine,
      37% of the J-pouch subjects with subtotal to total villous atrophy had osteopenia
      (Z score <-1), whereas none of the subjects with normal villous structure had
      reduced bone densities in the spine or femoral neck. The highest prevalence of
      osteopenia (66.7%) and the lowest spine (mean -0.89+/-0.36; P = 0.006) and
      femoral neck (mean -0.63+/-0.29; P = 0.07) Z scores were found among the patients
      (n = 12) with inflammation in the proximal limb of the pouch. No biochemical
      parameters were found to predict osteopenia and in stepwise regression analysis,
      the only independent risk factors for osteopenia were low body mass index and
      villous atrophy. CONCLUSIONS: Patients with a J-pouch showing high inflammatory
      activity and villous atrophy in the pouch need long-term follow-up and should be
      ensured adequate intake of calcium and vitamin D.

PMID- 11843055
TI  - Colonic production of nitric oxide gas in ulcerative colitis, collagenous colitis
      and uninflamed bowel.
AB  - BACKGROUND: Nitric oxide (NO) produced in excess by the inflamed human colon is
      generally considered a pathway of mucosal damage. In an attempt to quantify
      colonic mucosal production of NO in various forms of colitis we performed 'steady
      state' gas perfusion of whole colon in 11 patients with ulcerative colitis, 10
      patients with collagenous colitis and 20 controls with uninflamed mucosa.
      METHODS: The tip of a Teflon tube was placed in the caecum during colonoscopy.
      Subsequently, argon was infused at a constant rate for 70-180 min. Argon and NO
      in gas sampled from the rectum were measured by neutron activation analysis and
      the chemiluminescence technique, respectively. RESULTS: The use of argon as a
      marker of colonic NO output was justified by complete recovery (96%+/-2; mean +/-
      s(x); n = 5) of argon in gas collected from the rectum and a constant output of
      NO at varying perfusion rates (25, 50 and 75 ml/min coefficient of variation 21%;
      n = 6). In patients with ulcerative colitis, colonic output of NO was 10-fold
      higher (P < 0.001) than in controls and positively correlated (P < 0.01) to
      indices of disease activity. In patients with collagenous colitis, colonic output
      of NO was 50-fold higher (P < 0.01) than in controls during periods with watery
      diarrhoea (n = 6), but within the range observed in ulcerative colitis in the
      absence of diarrhoea (n = 4). CONCLUSIONS: Argon gas perfusion of whole colon
      using chemiluminescence technique for measurement of NO is a reliable method for
      quantification of colonic mucosal NO production. Increased colonic production of
      NO in collagenous colitis, which exceeds the output observed even in extensive
      ulcerative colitis, militates against the theory that NO per se is a cause of
      mucosal injury.

PMID- 11843056
TI  - A polymorphism in the CD14 gene is associated with Crohn disease.
AB  - BACKGROUND: Inflammatory bowel diseases (IBD) are multifactorial disorders,
      characterized by failure to limit the inflammatory response to luminal antigens.
      Although genetic factors play an important role in the pathogenesis, little is
      known about the genes accountable. Immune response to intestinal bacteria seems
      to be crucial in the pathogenesis of IBD. METHODS: To evaluate the role of the
      CD14 gene in IBD, a functionally relevant polymorphism in the promoter region
      (T/C at position -159) has been genotyped in 219 patients with Crohn disease
      (CD), 142 patients with ulcerative colitis (UC) and 410 healthy controls by RFLP
      analysis. RESULTS: T allele and TT genotype frequencies were found increased in
      CD patients compared to controls (Pc=0.044 and 0.005, respectively). CONCLUSION:
      An altered immune response to LPS seems to play a role in the genetic
      predisposition to CD but not to UC.

PMID- 11843057
TI  - Vitamin D status, parathyroid hormone and bone mineral density in patients with
      inflammatory bowel disease.
AB  - BACKGROUND: Although the pathogenesis of osteoporosis in inflammatory bowel
      disease (IBD) is not established, vitamin D deficiency and disturbances in
      calcium metabolism are thought to be of importance, especially in Crohn disease
      (CD). Vitamin D status is assessed and the relation between indices of calcium
      metabolism, including 25-hydroxyvitamin D and parathyroid hormone concentrations.
      and bone mineral density (BMD) in CD and ulcerative colitis (UC) are examined.
      Sixty patients with CD and 60 with UC were investigated. Each group comprised 24
      men and 36 women. METHODS: Vitamin D metabolites, parathyroid hormone and
      biochemical markers of bone metabolism were measured in blood and urine. Lumbar
      spine, femoral neck and total body BMD were measured by dual X-ray absorptiometry
      (DXA) and Z-scores were obtained by comparison with age- and sex-matched normal
      values. RESULTS: Vitamin D deficiency (25-hydroxyvitamin D3 <30 nmol/l) was
      present in 27% of patients with CD and in 15% with UC. Furthermore, CD patients
      had a significantly lower mean concentration of 25-hydroxyvitamin D3 compared
      with UC patients. Vitamin D status was not related to BMD at any of the skeletal
      sites measured. Secondary hyperparathyroidism was found in 10 out of 27 patients
      with CD after small-bowel resections. No differences were found in serum
      osteocalcin and urine pyridinoline between patients with CD and those with UC.
      CONCLUSIONS: Hypovitaminosis D is common in CD patients. Patients with CD and
      small-bowel resections are at risk of developing secondary hyperparathyroidism
      and low BMD.

PMID- 11843058
TI  - Biopsy pathology predicts patients with ulcerative colitis subsequently requiring
      surgery.
AB  - BACKGROUND: The clinical course of patients with ulcerative colitis (UC) is
      unpredictable, and 17%-38% ultimately require surgery. We hypothesized that
      mucosal histology may differ between patients requiring surgery and those
      receiving medication alone. The aim of this study was to elucidate comprehensive
      criteria consisting of specific histologic features enabling the prediction of
      failure to medical treatment. METHODS: We studied colorectal biopsy specimens
      from 67 patients ultimately requiring surgery (UC-S) and 90 receiving medication
      alone for more than 3 years (UC-M), and conducted multiple logistic regression
      analysis on 70 histologic features together with endoscopic disease extent and
      patient age. The analysis constructed an equation finding probability of UC-S
      (P(UC-S)). Based on a receiver-operating characteristic curve, we selected four
      cut-off values of P(UC-S), and determined criteria of five categories: highest
      risk, higher-risk, unpredictable, lower-risk and lowest-risk of surgery.
      Sensitivity and specificity of criteria were evaluated in a 2 x 5 table. RESULTS:
      Statistically significant features predicting UC-S were deep ulceration (X1),
      frequent crypt abscesses (X2), focal and segmental mononuclear cell infiltration
      (X3 and X4), paucity of eosinophils (X5: eosinophil infiltration) and wide extent
      of the disease (X6). The regression equation was as follows: logitP(UC-S) = 
      16.26 + 3.20X1 + 4.83X2 + 11.65X3 + 5. 10X4 - 5.59X5 + 5.53X6. Higher-risk and
      lower-risk showed sensitivity exceeding 91.0% and specificity exceeding 98.5% in
      predicting the outcome. CONCLUSIONS: Our criteria incorporating specific
      histologic features and endoscopic disease extent reliably predict eventual
      clinical outcome, and are expected to prove useful in determining the necessity
      of surgery.

PMID- 11843059
TI  - The phosphodiesterase inhibitor, pentoxifylline, alters rat intestinal epithelial
      cell proliferation via changes in the expression of transforming growth factors.
AB  - BACKGROUND: Phosphodiesterase (PDE) inhibitors, among which pentoxifylline (PTX),
      are candidate molecules for the treatment of TNF-alpha-dependent inflammatory
      diseases. Based on the controversial effects of PTX observed in experimentally
      induced colitis, the aim of this work was to analyse its influence on intestinal
      epithelial cell proliferation and growth factor expression using the well
      established IEC18 cell line. METHODS: The effects of PTX, and of an activation
      (addition of dibutyryl-cAMP, db-cAMP) or inhibition (by a specific cAMP-protein
      kinase inhibitor, PKI) of the cAMP pathway, were examined after 3 days of
      culture. The IEC18 cell proliferation and [3H] thymidine incorporation, as well
      as the expression of TGF-alpha, TGF-beta1 and -beta2 mRNAs, were analysed in
      basal culture conditions and in the presence of the pro-inflammatory cytokine,
      TNF-alpha. RESULTS: PTX, like exogenous db-cAMP, inhibited in a dose-dependent
      manner the basal and TNF-alpha-modulated IEC18 cell proliferation; this effect
      was partly prevented by PKI. We confirmed that PTX induced a dose-related
      increase in intracellular cAMP. Concomitantly, the expression of TGF-alpha mRNA
      dropped and that of TGF-beta2 increased. Addition of db-cAMP instead of PTX also
      decreased TGF-alpha mRNA, but did not change TGF-beta2 transcripts. The decrease
      in the expression of TGF-alpha mRNA caused by PTX and db-cAMP was completely
      abolished by PKI; in contrast, TGF-beta2 remained unaltered. Yet, anti-TGF-beta2
      antibodies partially restored the PTX-inhibited cell proliferation. CONCLUSION:
      The phosphodiesterase inhibitor, PTX, inhibits IEC18 cell proliferation via a
      differential modulation of TGF-alpha and TGF-beta2 expression. The drop in TGF
      alpha mRNA is related to increasing intracellular cAMP, whereas the effect upon
      TGF-beta2 appears cAMP-independent.

PMID- 11843060
TI  - Effects of lactic acid bacteria on the uptake and distribution of the food
      mutagen Trp-P-2 in mice.
AB  - BACKGROUND: Lactic acid bacteria have been reported to have antimutagenic and
      anticarcinogenic properties in vivo and in vitro. Lactobacillus acidophilus and
      Bifidobacterium longum have earlier been shown to bind the food mutagen Trp-P-2
      in vitro. METHODS: The influence of oral supplementation with L. acidophilus NCFB
      1748 and B. longum BB 536 on the uptake and distribution of 14C-labelled Trp-P-2
      in several mouse tissues was quantified by liquid scintillation measurements and
      examined by tape section autoradiography (gives an unbiased qualitative
      registration of differences in overall tissue distribution) in the present
      investigation. Furthermore, the effect of 13-naphthoflavone (BNF), a cytochrome
      P4501A (CYP1A)-inducing agent, on the distribution of 14C-labelled Trp-P-2 was
      examined. RESULTS: After oral (6 mg/kg; 5 microCi) or iv (1.2 mg/kg; 1 microCi)
      administration of 14C-labelled Trp-P-2, high levels of radioactivity were
      observed in the bile, urine and contents of the gastrointestinal tract. Lower
      levels were present in the liver, lung, kidney, intestines, brown fat,
      submaxillary salivary gland and thymus. In mice supplemented with lactic acid
      bacteria there was a significantly decreased level (29%-73%) of radioactivity in
      the lung, thymus, liver, kidney, submaxillary salivary gland and small intestine
      as compared with controls. In mice pretreated with BNF, a low but distinct
      localization of radioactivity in the lung was observed, whereas no similar
      localization occurred in controls. CONCLUSIONS: The results suggest that (i)
      there is a decreased bioavailability of the Trp-P-2 in the majority of the
      tissues examined in bacteria supplemented mice and (ii) there is a low but
      distinct CYP1A-dependent activation of Trp-P-2 in the lung of BNF-treated mice.

PMID- 11843062
TI  - Effect of combined interferon-alpha induction therapy and ribavirin on chronic
      hepatitis C virus infection: a randomized multicentre study.
AB  - BACKGROUND: The efficacy of interferon-alpha (IFN) induction in combination with
      ribavirin for chronic hepatitis C virus (HCV) infection is not known. METHODS: A
      total of 256 treatment-naive HCV RNA-positive patients with biopsy-confirmed
      chronic hepatitis were enrolled in a randomized multicentre study. The patients
      received either standard combination therapy with 3 MIU interferon-alpha2b thrice
      weekly for 26 weeks or 6 MIU interferon-alpha2b daily for 4 weeks and 3 MIU 3/7
      days for 22 weeks. All patients received ribavirin 1000 mg or 1200 mg (weight
      dependent) daily during the 26-week treatment period. Patients were monitored for
      HCV RNA during and following treatment. RESULTS: The sustained virological
      response rates (26 weeks after end of treatment) were 54% and 47% for patients
      receiving IFN induction/ribavirin and standard IFN/ribavirin, respectively (P =
      0.35). Among patients infected with genotype 1a/1b, the sustained response rates
      were 32% and 35%. In patients infected with genotype 2b/3a IFN
      induction/ribavirin led to a sustained response rate of 80% as compared to 65% in
      the standard combination therapy group (P = 0.073). Steatosis was more frequently
      seen in liver biopsies from patients infected with genotype 3a as compared to
      genotypes la/lb. Among genotype 1a/1b infected patients. steatosis was a highly
      significant predictor of failure to achieve sustained virological response.
      Logistic regression analysis (multivariate analysis) showed that independent
      predictors of sustained virological response were low age, female gender,
      genotype 2b/3a and HCV RNA negativity at 2 weeks. CONCLUSIONS: IFN induction in
      combination with ribavirin does not increase the sustained virological response
      rate among patients infected with HCV. Absence of steatosis is an independent
      predictor of sustained virological response in patients infected with genotypes
      1a/1b.

PMID- 11843061
TI  - Absence of therapeutic efficacy of the somatostatin analogue lanreotide in
      advanced primary hepatic cholangiocellular cancer and adenocarcinoma of the
      gallbladder despite in vivo somatostatin-receptor expression.
AB  - BACKGROUND: Carcinoma of the biliary system is a rare tumour entity, and patients
      with advanced disease face a dismal prognosis. Because of the absence of standard
      chemotherapy for advanced biliary carcinoma and reports of expression of
      receptors for somatostatin (SST), we performed a phase II study to evaluate the
      clinical potential of the long-acting SST analogue lanreotide (LAN) for treatment
      of this disease. METHODS: Twenty consecutive patients with histologically
      verified primary hepatic cholangiocellular cancer or primary adenocarcinoma of
      the gallbladder were enrolled in the study. Before initiation of therapy, SST
      receptor scintigraphy using 111In-DOTA-LAN was carried out in eight patients to
      check for in vivo expression of SST receptors. Thirty milligrams of a slow
      release formulation of LAN was administered by deep intramuscular injection every
      2 weeks until progression or patients wished to withdraw. Restaging by means of
      computed tomography was performed every 8 weeks, and response was assessed
      according to World Health Organisation standard criteria. In addition, weight,
      performance status, analgesic intake and subjective pain perception were recorded
      every 4 weeks, along with evaluation of tumour markers CEA and Ca 19-9. RESULTS:
      Tumour sites were visualized by means of 111In-DOTA-LAN in all 8 patients. A
      total of 161 injections were administered, the median number per patient being 5
      (range 2-36). Side effects were generally mild, only two patients complained of
      mild nausea and one patient had meteorism attributed to therapy. Therapeutic
      results, however, were disappointing, with only one patient demonstrating
      complete remission (CR), which lasted for 18 months before diagnosis of
      recurrence. Four patients had stable disease (SD) lasting between 3.5 and 9+
      months accompanied by weight gain and improvement in performance status in 2
      cases, while the remaining 15 patients progressed during therapy. The median time
      to progression was 2.5 months (range 1-18), and the median survival was 4.5
      months (range 1.5-18+ months). No clear-cut correlation between scan result and
      therapeutic outcome could be demonstrated, as not only the patient with CR and
      two with SD, but also five patients with progressive disease had a positive scan
      result. CONCLUSION: Our data show that adenocarcinomas of the gallbladder and
      hepatic cholangiocellular carcinomas express SST receptors in vivo as judged by
      111In-DOTA-LAN scintigraphy. Despite this fact, LAN did not display therapeutic
      activity in this study.

PMID- 11843063
TI  - Transforming growth factor-beta 1, activin and follistatin in patients with
      hepatocellular carcinoma and patients with alcoholic cirrhosis.
AB  - BACKGROUND: Transforming growth factor-beta 1 (TGF-beta1) exerts an inhibitory
      effect on DNA synthesis in hepatocytes. Activin, through different mechanisms,
      also exhibits an apoptotic effect on hepatocytes. Follistatin antagonizes the
      actions of activin. METHODS: Patients with hepatocellular carcinoma (HCC, n =
      20), patients with alcoholic cirrhosis (n = 12), patients with cirrhosis due to
      other causes (n = 5) and normal controls (n = 19) were studied. TGF-beta1,
      activin and follistatin concentrations in blood and ascites were measured by
      ELISA. RESULTS: All three groups of patients had significantly higher serum
      levels of total TGF-beta1, activin and follistatin compared to those of controls.
      In patients with HCC, the total TGF-beta1 level correlated negatively with tumour
      size (r = -0.644, P = 0.001). The activin level correlated with alkaline
      phosphatase (ALP) level (r = 0.374, P = 0.046). The follistatin level correlated
      with the ALP level (r = 0.404, P = 0.026), and the glutamyl transpeptidase level
      (r = 0.457, P = 0.01). In patients with alcoholic cirrhosis, serum activin
      correlated with the Child-Pugh score (r = 0.601, P = 0.01). The levels of the
      cytokines in ascites (n = 16) did not correlate with the corresponding levels in
      serum. CONCLUSIONS: Serum levels of total TGF-beta1, activin and follistatin were
      elevated in patients with hepatocellular carcinoma and in patients with alcoholic
      cirrhosis. Apoptosis of tumour cells may be reduced by a subsequent decrease in
      serum TGF-beta1 levels when the tumours expand in size. Activin and follistatin
      were associated with tumour activity, as both correlated with ALP and/or GGT
      levels. Further studies are required to define the exact relationships between
      these cytokines, the dynamics of tumour growth and their significance in
      cirrhosis.

PMID- 11843064
TI  - Interleukin-17 stimulates chemokine (interleukin-8 and monocyte chemoattractant
      protein-1) secretion in human pancreatic periacinar myofibroblasts.
AB  - BACKGROUND: Interleukin (IL)-17 is a newly identified T-cell-derived cytokine
      that can regulate the functions of a variety of cell types. In this study, we
      investigated the effects of CD4+ T-cell-derived cytokines on chemokine secretion
      in human pancreatic periacinar myofibroblasts. METHODS: The secretion of IL-8 and
      monocyte chemoattractant protein (MCP)-1 was evaluated by ELISA and Northern
      blot. The expression of IL-17 receptor (R) was analyzed by Northern blot and a
      binding assay using 125I-labeled IL-17. The activation of nuclear factor-kappaB
      (NF-kappaB) was assessed by an electrophoretic gel mobility shift assay (EMSA).
      RESULTS: IL-17 induced a dose-dependent increase in IL-8 and MCP-1 secretion. The
      effects of IL-17 on IL-8 and MCP-1 mRNA abundance reached a maximum as early as 3
      h. and then gradually decreased. IL-17 and IFN-gamma synergistically increased IL
      8 secretion and additively enhanced MCP-1 secretion. IFN-gamma induced a weak
      increase in IL-17R mRNA abundance, but incubation with IFN-gamma for 24 h had no
      effects on 125I-labeled IL-17-binding, indicating that the co-stimulatory effects
      of IL-17 and IFN-gamma were not regulated by the modulation of IL-17R expression.
      Furthermore, IL-17 induced a rapid increase in NF-kappaB DNA-binding activity,
      and the combination of IL-17 and IFN-gamma further enhanced NF-kappaB DNA-binding
      activity. CONCLUSIONS: In conclusion, it becomes clear that IL-17 is an inducer
      of IL-8 and MCP-1 secretion in human pancreatic periacinar myofibroblasts. The
      combination of IL-17 with IFN-gamma further enhances chemokine secretion. These
      findings indicate a linkage between T-cell-mediated immunity and inflammatory
      responses in the pancreas.

PMID- 11843065
TI  - Management of enterochromaffin-like gastric carcinoid tumour metastasized to the
      liver.
AB  - We report the rare case of a patient suffering from pernicious anaemia and a
      history of flushing and diarrhoea. The patient was found to have microcarcinoids
      with multiple gastric polyps and a solitary liver metastasis. He was successfully
      managed with subtotal gastrectomy, while the liver metastasis was cured by
      Interferon-alpha and octreotide administration.

PMID- 11843066
TI  - Age-related working memory impairments in children with prefrontal dysfunction
      associated with phenylketonuria.
AB  - The prefrontal cortex of the brain has been shown to play a crucial role in
      working memory, and age-related changes in prefrontal function may contribute to
      the improvements in working memory that are observed during childhood. We
      examined the developmental trajectory of working memory in school-age children
      with early-treated phenylketonuria (PKU), a metabolic disorder that results in
      prefrontal dysfunction. Using a recognition procedure, we evaluated working
      memory for letters, abstract objects, and spatial locations in 20 children with
      PKU and 20 typically developing control children. Children in both groups ranged
      from 6 to 17 years of age. Our findings revealed poorer performance across all
      three types of materials for children with PKU. In addition, there was a
      significant difference in the developmental trajectory of working memory for
      children with PKU as compared with controls. Specifically, deficits were not
      apparent in younger children with PKU. Instead, deficits were observed only in
      older children, suggesting the presence of a developmental deficit rather than a
      developmental delay in the working memory of children with PKU.

PMID- 11843067
TI  - Crossover is not a consequence of neglect: a test of the orientation/estimation
      hypothesis.
AB  - Most patients with neglect demonstrate a crossover effect on line bisection.
      Crossover refers to a pattern of performance in which long lines (>10 cm) are
      bisected ipsilateral to brain injury and short lines (<2 cm) are bisected
      contralateral to brain injury. Crossover bisections on short lines are of
      interest because they are not predicted by contemporary theories concerning
      neglect. However, we propose that the effect depends on two independent factors
      that normally influence bisection performance but are merely exaggerated in
      neglect--a tendency to overestimate the length of short lines and underestimate
      long lines and a tendency to orient attention preferentially in one spatial
      direction. We predicted that both patients with unilateral left and right
      hemisphere injury would demonstrate crossover on line bisection and that they
      would overestimate short lines and underestimate long lines upon direct visual
      inspection. Further, the 2 groups were predicted to demonstrate crossover in
      opposite directions owing to different lesion-induced biases in attentional
      orientation. Testing 5 patients with right hemisphere injury and 7 patients with
      left hemisphere injury confirmed each prediction. Additionally, errors in length
      estimation were exaggerated among patients with right hemisphere injury, most of
      whom had neglect. It is concluded that while crossover is accentuated in cases of
      neglect, it is not a consequence of neglect per se. As such, crossover bisections
      are not at odds with contemporary neglect theory.

PMID- 11843068
TI  - Attentional processes and their remediation in children treated for cancer: a
      literature review and the development of a therapeutic approach.
AB  - It is now generally accepted that central nervous system treatments for childhood
      cancer can result in significant cognitive impairment, most commonly in the areas
      of attention/concentration. We review the literature on attentional and
      neurocognitive deficits in this population, and also efforts to remediate
      attentional deficits in other brain injured populations. It was our goal to
      develop an innovative, psychologically based outpatient rehabilitation program
      that would improve dysfunctional attentional processes and associated
      neuropsychological deficits. The characteristics of this program and a pilot
      study of its effectiveness are described. Participants were 31 off-therapy cancer
      survivors with documented attention deficits. Twenty-one completed the cognitive
      remediation program (CRP) and 10 served as comparisons. All participants
      completed a test of vigilance attention, 2 tests with an attentional component,
      and an arithmetic academic achievement measure. When the scores of the 2 groups
      were compared, the CRP group exhibited statistically significant improvement on
      all attentional measures. In contrast, the comparison group did not manifest any
      significant changes. Neither group demonstrated statistically significant changes
      on the arithmetic achievement test. We believe that the CRP has potential for
      improving attention/concentration, but generalization to academic achievement
      remains unproven. Phase 3 clinical trials and the documentation of long-term
      treatment gains are needed. Furthermore, it will be necessary to demonstrate the
      ecological validity of the CRP. With these caveats, this therapeutic approach may
      be helpful in other populations of cognitively impaired children and young
      adults, such as patients who have suffered traumatic brain injury.

PMID- 11843069
TI  - Visual attention in preschool children prenatally exposed to cocaine:
      implications for behavioral regulation.
AB  - The presence of cocaine during the prenatal period disrupts the development of
      neural systems involved in mediating visual attention; therefore, it is possible
      that prenatal cocaine exposure results in impairments in visual attention in
      early childhood. In the current study we hypothesized that preschool children
      with prenatal cocaine exposure would exhibit difficulties in the disengagement
      operation of visual attention and in sustaining attention, particularly for
      targets presented in the right visual field. Fourteen cocaine-exposed children
      and 20 control children between 14 and 60 months of age were assessed on measures
      of visual attention, cognition, and behavior. Cocaine-exposed children had slower
      reaction times on disengagement trials in the second half of our attention task,
      supporting our hypotheses that impairments in disengagement and sustained
      attention are associated with prenatal cocaine exposure. There was a trend for
      slower reaction times to targets presented in the right visual field, but not to
      targets presented in the left visual field. Cocaine-exposed children also
      exhibited greater difficulties in behavioral regulation. Overall, our findings
      suggest that children with prenatal cocaine exposure demonstrate specific
      impairments in visual attention and behavioral regulation.

PMID- 11843070
TI  - Cognitive functioning in individuals with "benign" essential tremor.
AB  - Essential tremor (ET) is the most common type of movement disorder, although its
      etiology and neurophysiological substrates remain unclear. While thought to be a
      benign condition, it has yet to be studied from a neuropsychological perspective.
      We examined the neurocognitive functioning of 13 nondemented subjects with severe
      ET, including aspects of memory, cognitive flexibility, and attention. Results
      revealed that 12/13 subjects demonstrated impairment on 1 or more cognitive
      measures in comparison with published normative data. The pattern of findings was
      suggestive of relative dysfunction of frontal-mediated processes not unlike that
      seen in Parkinson's disease. These deficits were found in subjects irrespective
      of the presence of cognitive complaints, depression, or the existence of other
      potential neurocognitive risk factors. These findings suggest that mild cognitive
      deficits are not uncommon in association with severe ET and may be related to
      subcortical systems.

PMID- 11843071
TI  - Emotional experience and perception in the absence of facial feedback.
AB  - The facial feedback hypothesis suggests that facial expressions are either
      necessary or sufficient to produce emotional experience. Researchers have noted
      that the ideal test of the necessity aspect of this hypothesis would be an
      evaluation of emotional experience in a patient suffering from a bilateral facial
      paralysis; however, this condition is rare and no such report has been
      documented. We examined the role of facial expressions in the determination of
      emotion by studying a patient (F.P.) suffering from a bilateral facial paralysis.
      Despite her inability to convey emotions through facial expressions, F.P.
      reported normal emotional experience. When F.P. viewed emotionally evocative
      slides her reactions were not dampened relative to the normative sample. F.P.
      retained her ability to detect, discriminate, and image emotional expressions.
      These findings are not consistent with theories stating that feedback from an
      active face is necessary to experience emotion, or to process emotional facial
      expressions.

PMID- 11843073
TI  - Perception of illness: nonspecificity of postconcussion syndrome symptom
      expectation.
AB  - A growing number of studies show postconcussion syndrome (PCS) symptom report is
      influenced by factors other than head injury, suggesting symptoms typically
      associated with PCS may not be specific to head injury. Given the role that
      symptom expectation has been hypothesized to play in PCS symptom etiology, a
      comparison of symptoms expected for various disorders seems overdue. The present
      study asked 82 undergraduates to report the symptoms they currently experience,
      and then to report the symptoms they would expect to experience if they had had
      suffered either a head injury, an orthopedic injury, posttraumatic stress, or
      depression. No current differences in overall symptoms or in symptom subscales
      emerged. Results showed individuals portraying head injury, posttraumatic stress,
      and depression expected an increase in total symptoms, though individuals
      portraying an orthopedic injury did not expect such an increase. Results also
      showed simulators of head injury, posttraumatic stress, and depression expected
      equivalent rates of overall symptoms, memory/cognitive complaints, somatic
      concerns, and distracter symptoms, though head-injured individuals reported fewer
      affective symptoms than those portraying psychological disorders. In all, these
      findings suggest that individuals have a relative lack of specificity in symptom
      expectation for various disorders, with the implication that symptom checklists
      for "PCS" may not be useful for diagnosis.

PMID- 11843072
TI  - Planum temporale asymmetry and ear advantage in dichotic listening in
      Developmental Dyslexia and Attention-Deficit/Hyperactivity Disorder (ADHD).
AB  - The planum temporale is clearly involved in language processing, for it serves as
      the auditory association cortex. Research has consistently demonstrated that 60
      to 70% of the population has leftward asymmetry of the planum temporale. Research
      has also suggested that dyslexic individuals tend to have either rightward
      asymmetry or symmetrical plana. Moreover, many studies have found a relationship
      between the presence of dyslexia and/or language impairment and deficits in the
      normal right ear advantage found in dichotic listening paradigms. In this
      context, this study examined the relationship between planum temporale asymmetry
      and ear preference in dichotic listening performance in children with
      Developmental Dyslexia and Attention-Deficit/Hyperactivity Disorder (ADHD).
      Subjects included 19 children with dyslexia (10 of whom had a comorbid diagnosis
      of ADHD), 23 children with ADHD, and 12 diagnosed normal control children.
      Dichotic listening data were not collected for 8 of the 12 normal control
      children and for 3 of the 23 ADHD children. Results revealed no significant
      difference between ADHD and dyslexic subjects in regard to ear advantage on the
      free recall dichotic listening task. In addition, although the directed dichotic
      listening tasks were not related to degree of planum asymmetry, as predicted,
      results indicated that subjects who consistently displayed an atypical left ear
      advantage tended to have larger right bank lengths than those who consistently
      displayed a typical right ear advantage. These findings support the notion that
      some individuals with dyslexia or language deficits tend to have a larger right
      planum temporale and that performance on dichotic listening tasks may reflect
      this relatively unusual pattern.

PMID- 11843074
TI  - Predicting functional performance by patients with Alzheimer's disease using the
      Problems in Everyday Living (PEDL) Test: a preliminary study.
AB  - Findings from a recent population-based survey indicate that about 33% of
      patients with dementia reside alone. Because many of these patients may not have
      a caregiver who visits them regularly, the need for a neuropsychological (NP)
      test to predict patients' functional competence to live alone safely is evident.
      In this study, we compared the accuracy of predicting Instrumental and Basic
      Activities (IADLs and ADLs) of 22 patients with Alzheimer's disease using several
      standard NP tests and the newly developed Problems in Everyday Living (PEDL)
      test. Performance of IADLs and ADLs as rated by caregivers was significantly
      correlated with performance on the PEDL, the Mini-Mental State Exam (MMSE), and
      with the Shipley Institute of Living Test of Verbal Abstraction (SILS-A), but not
      with vocabulary or naming. The PEDL was the best predictor of IADL scores (r =
      0.71), compared to the MMSE (r = 0.52) and the SILS-A (r = 0.57), while the MMSE
      was the best predictor of ADL performance (r = 0.69), compared to the PEDL (r =
      0.58) and the SILS-A (r = 0.50).

PMID- 11843075
TI  - Paired associate performance in the early detection of DAT.
AB  - Subjects underwent longitudinal neuropsychological assessment in order to
      retrospectively determine which measures of cognitive function best predicted
      later development of dementia of the Alzheimer type (DAT). Three groups of
      subjects were studied: normal controls, patients with early DAT, and questionable
      dementia subjects (QD). All subjects were assessed using a battery of standard
      neuropsychological measures and two subtests from the Cambridge
      Neuropsychological Test Automated Battery (CANTAB), paired associate learning and
      delayed matching to sample. A structured interview was also used to elicit a
      profile of the subject's daily functioning. Subjects were assessed every 6 months
      for 2 years. At the 6 month assessment, almost half of the QD group exhibited
      significant deterioration in scores on the computerized paired associate learning
      subtest, while maintaining their scores on standard measures. At the conclusion
      of the study, all of this QD subgroup fulfilled the NINCDS-ADRDA criteria for
      probable DAT pertaining to significant cognitive and functional deterioration.
      Performance on the C

PMID- 11843076
TI  - Mathematics skills in good readers with hydrocephalus.
AB  - Children with hydrocephalus have poor math skills. We investigated the nature of
      their arithmetic computation errors by comparing written subtraction errors in
      good readers with hydrocephalus, typically developing good readers of the same
      age, and younger children matched for math level to the children with
      hydrocephalus. Children with hydrocephalus made more procedural errors (although
      not more fact retrieval or visual-spatial errors) than age-matched controls; they
      made the same number of procedural errors as younger, math-level matched
      children. We also investigated a broad range of math abilities, and found that
      children with hydrocephalus performed more poorly than age-matched controls on
      tests of geometry and applied math skills such as estimation and problem solving.
      Computation deficits in children with hydrocephalus reflect delayed development
      of procedural knowledge. Problems in specific math domains such as geometry and
      applied math, were associated with deficits in constituent cognitive skills such
      as visual spatial competence, memory, and general knowledge.

PMID- 11843077
TI  - What do Alzheimer's disease patients know about animals? It depends on task
      structure and presentation format.
AB  - Deficits on tasks requiring semantic memory in Alzheimer's disease (AD) may be
      due to storage loss, a retrieval deficit, or both. To address this question, we
      administered multiple tasks involving 9 exemplars of the category "animals,"
      presented as both words and pictures, to 12 AD patients and 12 nondemented
      individuals. Participants made semantic judgments by class (sorting task),
      similarity (triadic comparison task), and dimensional attributes (ordering task).
      Relative to control participants, AD patients were impaired on an unstructured
      sorting task, but did not differ on a constrained sorting task. On the triadic
      comparison task, the patients were as likely to make judgments based on size as
      domesticity attributes, whereas control participants made judgments based
      primarily on domesticity. The patients' judgments were also less consistent
      across tasks than those of control participants. On the ordering tasks,
      performance was generally comparable between groups with pictures but not words,
      suggesting that pictures enable AD patients to access information from semantic
      memory that is less accessible with lexical stimuli. These results suggest that
      AD patients' semantic judgments are impaired when the retrieval context is
      unstructured, but perform normally under supportive retrieval conditions.

PMID- 11843079
TI  - Accelerator radiation protection.

PMID- 11843078
TI  - Object-based and action-based visual perception in children with spina bifida and
      hydrocephalus.
AB  - Children with spina bifida and hydrocephalus (SBH) have long been known to have
      difficulties with visual perception. We studied how children with SBH perform 12
      visual perception tasks requiring object identification, multistable
      representations of visual space, or visually guided overt actions. Four tasks
      required object-based processing (visual constancy illusions, face recognition,
      recognition of fragmented objects, line orientation). Four tasks required the
      representation of visual space in egocentric coordinates (stereopsis, visual
      figure-ground identification, perception of multistable figures, egocentric
      mental rotation). Four tasks required the coupling of visual space to overt
      movement (visual pursuit, figure drawing, visually guided route finding, visually
      guided route planning). Effect sizes, measuring the magnitude of the difference
      between SBH children and controls, were consistently larger for action-based than
      object-based visual perception tasks. Within action-based tasks, effect sizes
      were large and roughly comparable for tasks requiring the representation of
      visual space and for tasks requiring visually guided action. The results are
      discussed in terms of the physical and brain problems of children with SBH that
      limit their ability to build effective situation models of space.

PMID- 11843080
TI  - Radiation protection at low energy proton accelerators.
AB  - A sample is provided of the radiological safety issues particular to low energy
      proton accelerators. 'Low' energy in this context is taken to mean proton
      energies of less than about 1 GeV. Many of the radiation issues are common to all
      particle accelerators. Here, those issues are addressed that may require perhaps
      not unique treatment but those which benefit from a different approach. Among the
      problems discussed are the generation of prompt radiation and its transmission
      through shielding, the estimation of induced radioactivity, and the assessments
      of both the off-site prompt radiation hazard and the effect of releases of
      radioactive effluents to the environment.

PMID- 11843081
TI  - Radiation protection at high energy proton accelerators.
AB  - The radiological problems associated with proton accelerators having maximum
      energies higher than a few GeV are discussed. Examples are given from
      accelerators where the authors have had practical experience for a number of
      years. The main focus will be on those problems which are unique to high energy
      proton accelerators, and which may not be necessarily associated with the proton
      beam operation itself.

PMID- 11843082
TI  - Radiation protection and environmental management at the relativistic heavy ion
      collider.
AB  - The Relativistic Heavy Ion Collider (RHIC) is a high energy hadron accelerator
      built to study basic nuclear physics. It consists of two counter-rotating beams
      of fully stripped gold ions that are accelerated in two rings to an energy of 100
      GeV/nucleon or protons at 250 GeV/c. The beams can be stored for a period of five
      to ten hours and brought into collision for experiments during that time. The
      first major physics objective is to recreate a state of matter, the quark-gluon
      plasma, that has been predicted to have existed at a short time after the
      creation of the universe. Because there are only a few other high energy particle
      accelerators like RHIC in the world, the rules promulgated in the US Code of
      Federal Regulations under the Atomic Energy Act, State regulations, or
      international guidance documents do not cover prompt radiation from accelerators
      to govern directly the design and operation of a superconducting collider.
      Special design criteria for prompt radiation were developed to provide guidance
      tor the design of radiation shielding. Environmental Management at RHIC is
      accomplished through the ISO 14001 Environmental Management System. The
      applicability, benefits, and implementation of ISO 14001 within the framework of
      a large research accelerator complex are discussed in the paper.

PMID- 11843083
TI  - Radiation protection at high energy electron accelerators.
AB  - An overview is presented of radiation protection at high energy electron
      accelerator facilities. By 'high energy' is meant the energy domain beyond a few
      tens of MeV, where electromagnetic showers are the determining and dominant
      factor for beam interactions with matter. The basic components of electron
      accelerators are described and their potential impact on radiation safety. The
      paper then concentrates on sources of prompt radiation which distinguish these
      machines from other accelerator facilities and briefly describe other features
      such as shielding or safety systems as relevant to electron machines. A more
      comprehensive description of these aspects can be found elsewhere in these
      proceedings. In addition, general concepts presented in this review are
      complemented and illustrated by specific examples in the authors' synchrotron
      radiation work in these proceedings.

PMID- 11843085
TI  - Shielding high energy accelerators.
AB  - After introducing the subject or shielding high energy accelerators, point
      source, line-of-sight models, and in particular the Moyer Model, are discussed.
      Their use in the shielding of proton and electron accelerators is demonstrated
      and their limitations noted, especially in relation to shielding in the forward
      direction provided by large, flat walls. The limitations of reducing problems to
      those using a cylindrical geometry description are stressed. Finally the use of
      different estimators for predicting dose is discussed. It is suggested that dose
      calculated from track-length estimators will generally give the most satisfactory
      estimate.

PMID- 11843084
TI  - Radiation protection at synchrotron radiation facilities.
AB  - A synchrotron radiation (SR) facility typically consists of an injector, a
      storage ring, and SR beamlines. The latter two features are unique to SR
      facilities, when compared to other types of accelerator facilities. The SR
      facilities have the characteristics of low injection beam power, but high stored
      beam power. The storage ring is generally above ground with people occupying the
      experimental floor around a normally thin concrete ring wall. This paper
      addresses the radiation issues, in particular the shielding design, associated
      with the storage ring and SR beamlines. Normal and abnormal beam losses for
      injection and stored beams, as well as typical storage ring operation, are
      described. Ring shielding design for photons and neutrons from beam losses in the
      ring is discussed. Radiation safety issues and shielding design for SR beamlines,
      considering gas bremsstrahlung and synchrotron radiation, are reviewed. Radiation
      source terms and the methodologies for shielding calculations are presented.

PMID- 11843087
TI  - Special radiation protection aspects of medical accelerators.
AB  - Radiation protection aspects relevant to medical accelerators are discussed. An
      overview is first given of general safety requirements. Next, shielding and
      labyrinth design are discussed in some detail for the various types of
      accelerators, devoting more attention to hadron machines as they are far less
      conventional than electron linear accelerators. Some specific aspects related to
      patient protection are also addressed. Finally, induced radioactivity in
      accelerator components and shielding walls is briefly discussed. Three classes of
      machines are considered: (1) medical electron linacs for 'conventional' radiation
      therapy, (2) low energy cyclotrons for production of radionuclides mainly for
      medical diagnostics and (3) medium energy cyclotrons and synchrotrons for
      advanced radiation therapy with protons or light ion beams (hadron therapy).

PMID- 11843088
TI  - Radiation protection at medical accelerators.
AB  - This paper focuses on radiation protection at proton and light ion accelerators
      for radiotherapy. The National Centre of Hadrontherapy, which is planned to he
      built in Italy in the next five years, is considered as a reference facility for
      applying the various methodologies presented. The shielding design is firstly
      discussed, together with that of the access maze to the treatment rooms.
      Subsequently, the main aspects for the estimate of the air activation in the
      environment hosting the accelerator system are described. The estimate of the
      dose equivalent due to the activated air transferred to the neighbourhood
      population is also treated. Outlines are given of the radioactivity induced by
      the primary beam in the materials constituting the magnets and the patient's
      personal collimator.

PMID- 11843086
TI  - Induced activity in accelerator structures, air and water.
AB  - A summary is given of several rules of thumb' which can be used to predict the
      formation and decay of radionuclides in the structure of accelerators together
      with the dose rates from the induced radioactivity. Models are also given for the
      activation of gases (air of the accelerator vault) and liquids (in particular
      cooling water), together with their transport from the activation region to the
      release point.

PMID- 11843089
TI  - The impact of ICRP/ICRU quantities on high energy neutron dosimetry: a review.
AB  - Unlike other fields of toxicology, radiation protection has a dual system of
      quantities, one set for assessment and the derivation of authorised limits and
      another set for monitoring radiation performance and compliance. Neutrons are an
      important or dominant constituent of the radiation field around high energy
      accelerators and the evolution of the radiation protection quantities used to
      measure neutrons is described. In 1990 ICRP introduced a new quantity, the
      effective dose. E. with which to express its protection limits. E represented a
      radical departure from previous advice of the Commission, particularly in the
      manner by which it weighted the absorbed dose deposited by high LET radiations.
      This advice had profound consequences for neutron dosimetry. Over the past decade
      analyses have revealed logical flaws and inconsistencies in the definition of
      effective dose. These are briefly discussed with most emphasis being placed on
      inconsistencies in radiation weighting. Suggestions are made with a view to
      resolving these inconsistencies.

PMID- 11843090
TI  - Determination of personal dose equivalents in accelerator radiation fields.
AB  - Values for the dose equivalent are required for radiation protection purposes,
      but determination of such values can be quite difficult for high energy
      radiations. The accurate determination of personal dose equivalents in
      accelerator radiation fields requires the propel use of appropriate radiological
      quantities and units, knowledge of the dose equivalent response of the personal
      dosemeters used, measurement or calculation of the fluence spectrum in the
      workplace and the fluence spectrum of the reference radiation used to calibrate
      the dosemeters, in addition to knowledge of the appropriate fluence-to-dose
      equivalent conversion coefficients. This information can then be used to select
      the appropriate dosemeters, set up the optimum calibration conditions, or to
      establish correction factors that account for differences in the calibration and
      workplace fluence spectra. High energy neutrons account for a significant
      fraction of the dose equivalent received by workers at accelerator facilities,
      and this work discusses the procedures and methods needed to determine dose
      equivalent produced by neutrons in the vicinity of high energy particle
      accclerators.

PMID- 11843091
TI  - Radiation safety systems for accelerator facilities.
AB  - The radiation safety system RSS) of an accelerator facility is used to protect
      people from prompt radiation hazards associated with accelerator operation. The
      RSS is a fully interlocked, engineered system with a combination of passive and
      active elements that are reliable, redundant and fail-safe. The RSS consists of
      the access control system (ACS) and the radiation containment system (RCS). The
      ACS is to keep people away from the dangerous radiation inside the shielding
      enclosure. The RCS limits and contains the beam/radiation conditions to protect
      people from the prompt radiation hazards outside the shielding enclosure in both
      normal and abnormal operations. The complexity of an RSS depends on the
      accelerator and its operation. as well as associated hazard conditions. The
      approaches of RSS among different facilities can be different. This report gives
      a review of the RSS for accelerator facilities.

PMID- 11843092
TI  - The history and future of accelerator radiological protection.
AB  - The development of accelerator radiological protection from the mid-1930s, just
      after the invention of the cyclotron, to the present day is described. Three
      major themes--physics, personalities and politics--are developed. In the sections
      describing physics the development of shielding design though measurement,
      radiation transport calculations, the impact of accelerators on the environment
      and dosimetry in accelerator radiation fields are described. The discussion is
      limited to high-energy, high-intensity electron and proton accelerators. The
      impact of notable personalities on the development of both the basic science and
      on the accelerator health physics profession itself is described. The important
      role played by scholars and teachers is discussed. In the final section. which
      discusses the future of accelerator radiological protection, some emphasis is
      given to the social and political aspects that must he faced in the years ahead.

PMID- 11843093
TI  - Community interventions to promote healthy social environments: early childhood
      development and family housing. A report on recommendations of the Task Force on
      Community Preventive Services.
AB  - The sociocultural environment exerts a fundamental influence on health.
      Interventions to improve education, housing, employment, and access to health
      care contribute to healthy and safe environments and improved community health.
      The Task Force on Community Preventive Services (the Task Force) has conducted
      systematic reviews of early childhood development interventions and family
      housing interventions. The topics selected provide a unique, albeit small,
      beginning of the review of evidence that interventions do effectively address
      sociocultural factors that influence health. Based on these reviews, the Task
      Force strongly recommends publicly funded, center-based, comprehensive early
      childhood development programs for low-income children aged 3-5 years. The basis
      for the recommendation is evidence of effectiveness in preventing developmental
      delay, assessed by improvements in grade retention and placement in special
      education. The Task Force also recommends housing subsidy programs for low-income
      families, which provide rental vouchers for use in the private housing market and
      allow families choice in residential location. This recommendation is based on
      outcomes of improved neighborhood safety and families' reduced exposure to
      violence. The Task Force concludes that insufficient evidence is available on
      which to base a recommendation for or against creation of mixed-income housing
      developments that provide safe and affordable housing in neighborhoods with
      adequate goods and services. This report provides additional information
      regarding these recommendations, briefly describes how the reviews were
      conducted, and discusses implications for applying the interventions locally.

PMID- 11843094
TI  - Prostaglandin D2 in sleep-wake regulation: recent progress and perspectives.
AB  - Prostaglandin (PG) D2 is one of the most active endogenous sleep-promoting
      substances, which induces physiological sleep in rodents, primates, and most
      probably in humans as well. In this update article, we review recent experimental
      results concerning the molecular mechanisms underlying sleep-wake regulation by
      PGD2, the link between the humoral regulation by the PGD2 system, and the neural
      network involved in the promotion of non-rapid eye movement (NREM) sleep and the
      abnormality of NREM sleep regulation found in gene-manipulated mice for PGD
      synthase.

PMID- 11843095
TI  - Teaching neuroscience through Web adventures: adolescents reconstruct the history
      and science of opioids.
AB  - New technological and cultural developments surrounding adolescents' use of the
      World Wide Web offer an opportunity for turning aspects of the Internet gaming
      phenomenon to the advantage of neuroscience education. Specifically, an
      experimental project to transmit aspects of problem-based learning and the
      National Science Standards through an interactive Web adventure is reported here.
      The Reconstructors is an episodic Web-based adventure series entitled Medicinal
      Mysteries from History. It is funded by the National Institute on Drug Abuse, and
      the first series focuses on opioids. It was created with the input of middle
      school students and teachers. Through the use of multimedia technologies, middle
      school students enter a futuristic world in which they become "reconstructors,"
      members of an elite scientific unit charged with recovering lost medical
      knowledge about analgesic drugs. Two of the four episodes have been evaluated
      through a comprehensive review process involving middle school students,
      teachers, neuroscience researchers, and clinicians. Analysis of the pretest and
      posttest scores demonstrated significant knowledge gain that validly can be
      attributed to use of the game. These data provide evidence that science content
      can be transmitted through innovative online techniques without sacrificing
      compelling content or effective pedagogical strategies.

PMID- 11843096
TI  - Iron and Parkinson's disease.
AB  - Multiple studies implicate iron in the pathophysiology of Parkinson's disease
      (PD). In the brains of patients with PD, iron levels are elevated and the levels
      of iron-binding proteins are abnormal. Iron has been suspected to contribute to
      PD because Fe(II) is known to promote oxidative damage. Recent studies suggest
      that an additional mechanism by which iron might contribute to PD is by inducing
      aggregation of the alpha-synuclein, which is a protein that accumulates in Lewy
      bodies in PD.

PMID- 11843097
TI  - Recruiting the immune response to promote axon regeneration in the injured spinal
      cord.
AB  - Myelin contains molecules that can inhibit the growth and regeneration of axons.
      Neutralizing the activity of these inhibitors can enhance axon regeneration in
      the adult mammalian central nervous system (CNS). The complexity of the CNS
      immune system interactions after CNS trauma is now beginning to be better
      understood. Recent studies indicate that both cell-mediated and antibody-mediated
      immune responses can help in promoting axon regeneration after CNS injury. It is
      hoped that such advances will lead to the development of safe and effective
      vaccine and cytokine treatments for spinal cord injuries.

PMID- 11843098
TI  - How do we tell time?
AB  - Animals time events on scales that range more than 10 orders of magnitude-from
      microseconds to days. This review focuses on timing that occurs in the range of
      tens to hundreds of milliseconds. It is within this range that virtually all the
      temporal cues for speech discrimination, and haptic and visual processing, occur.
      Additionally, on the motor side, it is on this scale that timing of fine motor
      movements takes place. To date, psychophysical data indicate that for many tasks
      there is a centralized timing mechanism, but that there are separate networks for
      different intervals. These data are supported by experiments that show that
      training to discriminate between two intervals generalizes to different
      modalities, but not different intervals. The mechanistic underpinnings of timing
      are not known. However various models have been proposed, they can be divided
      into labeled-line models and population clocks. In labeled-line models, different
      intervals are coded by activity in independent and discrete populations of
      neurons. In population models, time is coded by the population activity of a
      large group of neurons, and timing requires dynamic interaction between neurons.
      Population models are generally better suited for parallel processing of
      interval, duration, order, and sequence cues and are thus more likely to underlie
      timing in the range of tens to hundreds of milliseconds.

PMID- 11843099
TI  - Neurotrophins and plasticity in the visual cortex.
AB  - The visual cortex is one of the favorite models for the study of experience
      dependent changes in neuronal structure and function. A number of recent
      investigations indicate that the neurotrophic factors of the nerve growth factor
      family (neurotrophins) play a pivotal role in visual cortical plasticity.
      Neurotrophins and their receptors are present in the cortex during the critical
      period for plasticity, and neurotrophin levels are regulated by electrical
      activity. Neurotrophins modulate synaptic transmission and patterns of neuronal
      connectivity in the cortex. This review summarizes the in vivo and in vitro data
      that demonstrate the involvement of neurotrophins in visual cortical plasticity
      and discusses the possible mechanisms of their action.

PMID- 11843100
TI  - Coding of objects in the prefrontal cortex in monkeys and humans.
AB  - The prefrontal cortex is an area of high-level association cortex that plays an
      important part in the processing of visual objects. In this update, we summarize
      recent experimental findings that have investigated object processing in the
      frontal cortex in monkeys and humans. We highlight several common themes that
      have emerged from the study of these different systems, including the short-term
      maintenance of object information in working memory and the processing of novel
      information. Together, these findings suggest that regions of the prefrontal
      cortex participate in the selection, maintenance, and evaluation of task-relevant
      attributes. At a larger level, the convergence of findings from monkey and human
      studies demonstrates that concurrent investigation of scientific questions in
      both species can be a fruitful approach and promises to lead to future advances.

PMID- 11843101
TI  - Cell death in the peripheral nervous system: potential rescue strategies.
AB  - Neuronal death occurs in many diseases of the peripheral nervous system including
      genetic, developmental, metabolic, degenerative, and toxic disorders. Specific
      diseases are mediated by one or several interlinked death-initiating pathways.
      These may involve oxidative stress, excitotoxicity, membrane disruption, loss of
      calcium homeostasis, DNA damage, trophic factor loss, or aberrant entry into the
      cell cycle. The death initiators activate two major final common pathways that
      lead to cell death. Necrosis is a catastrophic loss of ionic integrity caused by
      membrane disruption or loss of energy supply. Apoptosis is an endogenous
      programmed cell death pathway normally active in development and tissue
      homeostasis. It leads to orderly disassembly of the cell. Advances in
      understanding of the pathways from specific disease to neuronal death are leading
      to new strategies designed to prevent death and treat diseases of the nervous
      system.

PMID- 11843102
TI  - Cortical neurons that localize sounds.
AB  - Efforts to locate a cortical map of auditory space generally have proven
      unsuccessful. At moderate sound levels, cortical neurons generally show large or
      unbounded spatial receptive fields. Within those large receptive fields, however,
      changes in sound location result in systematic changes in the temporal firing
      patterns such that single-neuron firing patterns can signal the locations of
      sound sources throughout as much as 360 degrees of auditory space. Neurons in the
      cat's auditory cortex show accurate localization of broad-band sounds, which
      human listeners localize accurately. Conversely, in response to filtered sounds
      that produce spatial illusions in human listeners, neurons signal systematically
      incorrect locations that can be predicted by a model that also predicts the
      listeners' illusory reports. These results from the cat's auditory cortex, as
      well as more limited results from nonhuman primates, suggest a model in which the
      location of any particular sound source is represented in a distributed fashion
      within individual auditory cortical areas and among multiple cortical areas.

PMID- 11843103
TI  - A curriculum framework for nursing.
AB  - Nursing education has struggled for decades to develop a framework that would
      adequately reflect nursing and provide a stable yet dynamic curriculum for
      nursing education. Unfortunately, most of the frameworks the profession has used
      in the past either were adapted from other disciplines or based on processes,
      concepts, and theories that were too narrow to serve in the capacity of a
      unifying framework. Perhaps it is time that nursing begins to focus more on the
      profession's epistemological forest than on isolated trees when developing and
      selecting curricular frameworks. This article offers a framework that may help us
      do just that.

PMID- 11843104
TI  - A new perspective on competencies for self-directed learning.
AB  - In baccalaureate in nursing programs, self-directed methods of education have
      been used for many decades. A major goal of this type of approach to education is
      to provide students with the necessary competencies to become lifelong learners.
      Students must be exposed to self-directed learning competencies to obtain the
      knowledge, skills, and attributes unique to their personal and professional
      growth. It has been proposed that six competencies are required for students to
      become self-directed learners: self-assessment of learning gaps; evaluation of
      self and others; reflection; information management; critical thinking; and
      critical appraisal. Each of these skills are not mutually exclusive but are
      interrelated in such a way that students use all or a combination of them
      simultaneously to direct and control their learning.

PMID- 11843105
TI  - A congruent curriculum: philosophical integrity from philosophy to outcomes.

PMID- 11843106
TI  - The development of an organizing framework to implement AACN guidelines for
      nursing education. American Association of Colleges of Nursing.

PMID- 11843108
TI  - Challenges of teaching in an emancipatory curriculum.

PMID- 11843107
TI  - New curriculum for a new century: beyond repackaging.
AB  - A plan to evaluate the effectiveness of the changes is in progress. Focus groups
      with health care agencies in the community validate the life skills as essential
      to nursing practice. Evaluation of students and graduates is ongoing to determine
      the overall effectiveness of this curriculum. Preparing nurses for a new century
      requires developing a new curriculum. But it requires much more than changing
      what is taught. The students who are recruited, the teaching methods used, and
      the academic policies must be rethought. These all are reflected in this model
      that allows students to learn and practice skills needed for a lifetime in
      nursing.

PMID- 11843110
TI  - NCVEI core competency projects funded by board.

PMID- 11843109
TI  - Conceptual frameworks in undergraduate nursing curricula: report of a national
      survey.
AB  - A national survey was conducted to analyze the components of conceptual
      frameworks to assess how they are being used to organize the curricula of nursing
      programs and to determine whether there was a difference among types of programs
      (i.e., baccalaureate degree, associate degree, diploma). A stratified, random
      sample of 300 National League for Nursing Accrediting Committee-accredited
      schools of nursing was selected based on percentages of each type of program.
      Questionnaires were returned from 160 programs. The survey found that the
      conceptual frameworks of most nursing programs were eclectic and that the nursing
      process was the most commonly cited component for all types of programs.
      Significant differences were identified among the three types of programs in
      their use of simple-to-complex organization, the medical model, and the nursing
      process. Significant differences also were identified among the three types of
      programs in incorporation of the metaparadigm concepts of nursing, person,
      health, and environment, and the emphasis placed on critical thinking, problem
      solving, and therapeutic nursing interventions.

PMID- 11843111
TI  - Effect of reproductive status on intraocular pressure in cats.
AB  - OBJECTIVE: To measure intraocular pressure (IOP) and progesterone concentrations
      in cats and to examine their reproductive organs to determine whether
      reproductive status affects IOP in cats. ANIMALS: 75 sexually intact domestic
      shorthair cats scheduled to be neutered, including 28 males, 21 females not in
      estrus, 13 females in estrus, and 13 pregnant females. PROCEDURES: Applanation
      tonometry was conducted to measure IOP and radioimmunoassay was used to determine
      progesterone concentrations. Reproductive organs were examined at time of
      surgery. RESULTS: The IOP in female cats that were in estrus was significantly
      higher than IOP in female cats that were not in estrus. Progesterone
      concentrations significantly affected IOP in pregnant cats. CONCLUSIONS AND
      CLINICAL RELEVANCE: In cats, IOP is affected by changes in reproductive status.
      Such changes should be considered when interpreting tonometry results in this
      species.

PMID- 11843112
TI  - Associations between dietary factors in canned food and formation of calcium
      oxalate uroliths in dogs.
AB  - OBJECTIVE: To identify dietary factors in commercially available canned foods
      associated with the development of calcium oxalate (CaOx) uroliths in dogs.
      ANIMALS: 117 dogs with CaOx uroliths and 174 dogs without urinary tract disease.
      PROCEDURE: Case dogs were those that developed CaOx uroliths submitted to the
      Minnesota Urolith Center for quantitative analysis between 1990 and 1992 while
      fed a commercially available canned diet. Control dogs were those without urinary
      tract disease evaluated at the same veterinary hospital just prior to or
      immediately after each case dog. A content-validated multiple-choice
      questionnaire was mailed to each owner of case and control dogs with the
      permission of the primary care veterinarian. Univariate and multivariate logistic
      regressions for each dietary component were performed to test the hypothesis that
      a given factor was associated with CaOx urolith formation. RESULTS: Canned foods
      with the highest amount of protein, fat, calcium, phosphorus, magnesium, sodium,
      potassium, chloride, or moisture were associated with a decreased risk of CaOx
      urolith formation, compared with diets with the lowest amounts. In contrast,
      canned diets with the highest amount of carbohydrate were associated with an
      increased risk of CaOx urolith formation. CONCLUSIONS AND CLINICAL RELEVANCE:
      Feeding canned diets formulated to contain high amounts of protein, fat, calcium,
      phosphorus, magnesium, sodium, potassium, chloride, and moisture and a low amount
      of carbohydrate may minimize the risk of CaOx urolith formation in dogs.

PMID- 11843113
TI  - Evaluation of acetaminophen absorption in horses with experimentally induced
      delayed gastric emptying.
AB  - OBJECTIVE: To evaluate the correlation between the half-time of liquid-phase
      gastric emptying (T50) determined by use of nuclear scintigraphy, using
      technetiumTc 99m pentetate, and absorption variables of orally administered
      acetaminophen in horses with experimentally delayed gastric emptying. ANIMALS: 6
      mature horses. PROCEDURE: Delayed gastric emptying was induced by IV injection of
      atropine sulfate. Twenty minutes later, acetaminophen and technetium Tc 99m
      pentetate were administered simultaneously via nasogastric tube. Serial lateral
      images of the stomach region were obtained, using a gamma camera. Power
      exponential curves were used for estimation of T50 and modified R2 values for
      estimation of goodness-of-fit of the data. Serial serum samples were obtained,
      and acetaminophen concentration was determined, using fluorescence polarization
      immunoassay. Maximum serum concentration (Cmax), time to reach maximum serum
      concentration (Tmax), area under the curve for 480 minutes, and the appearance
      rate constant were determined, using a parameter estimation program. Correlations
      were calculated, using a Spearman rank correlation coefficient. RESULTS: A
      significant correlation was detected between T50 determined by use of
      scintigraphy and Tmax determined by use of acetaminophen absorption. Correlation
      between T50 and other absorption variables of acetaminophen was not significant.
      CONCLUSIONS AND CLINICAL RELEVANCE: The acetaminophen absorption method was a
      valid technique in this model of delayed gastric emptying in horses. The method
      may be a valuable tool for use in research as well as in clinical evaluation of
      gastric emptying in horses.

PMID- 11843114
TI  - Effects of adenosine pretreatment on detection of free radicals in ischemic and
      reperfused canine gracilis muscle flaps by use of spin-trapping electron
      paramagnetic resonance spectroscopy.
AB  - OBJECTIVE: To determine whether adenosine pretreatment attenuates free radical
      production and muscle damage in ischemic and reperfused canine skeletal muscle.
      ANIMALS: 9 healthy mixed-breed dogs. PROCEDURE: Dogs were anesthetized, and both
      gracilis muscles were isolated, leaving only the major vascular pedicle intact.
      Saline (0.9% NaCl) solution was injected into the artery supplying the control
      flap, whereas adenosine (10 mg) was injected into the contralateral artery.
      Ischemia was induced in both flaps for 4 hours. alpha-Phenyl-N-tert-butylnitrone
      was administered IV to each dog 1 hour prior to reperfusion. Following 15 minutes
      of reperfusion, effluent blood samples from each muscle flap were obtained and
      processed for spin-trapping electron paramagnetic resonance (EPR) spectroscopy.
      Muscle biopsy specimens were obtained for histologic evaluation, and dogs were
      euthanatized. RESULTS: EPR spectra of strong intensity were obtained from
      analysis of 5 of 9 paired samples. Signals identified were characteristic of
      oxygen- and carbon-centered free radical adducts. Signal intensity of spectra
      from adenosine-treated flaps was significantly less than that of control flaps;
      mean signal attenuation was 36% in the adenosine-treated group. Histologic
      evaluation of muscle flaps did not reveal significant differences between groups.
      CONCLUSIONS AND CLINICAL RELEVANCE: Treatment of canine muscle flaps with
      adenosine prior to a period of ischemia reduced but did not completely attenuate
      free radical production after reperfusion. However, adenosine pretreatment did
      not affect histologic abnormalities.

PMID- 11843115
TI  - Identification and concentration of soy isoflavones in commercial cat foods.
AB  - OBJECTIVE: To determine the absolute and relative soy isoflavone content in
      commercial cat foods. SAMPLE POPULATION: 14 dry, 6 semimoist, and 22 moist
      commercial cat foods. PROCEDURE: Soy isoflavone content of each food was
      determined by use of acid-methanol hydrolysis and high-pressure liquid
      chromatography with ultraviolet absorbance detection. Isoflavones were identified
      and quantified by reference to authentic standards. RESULTS: Genistein and
      daidzein were the major soy isoflavones identified in 24 of 42 foods, with
      concentrations ranging from 1 to 163 microg/g of food. Foods labeled as
      containing soybean solids (16/42) had isoflavone concentrations > 11 microg/g.
      More dry (13/14) and semimoist (6/6) foods contained isoflavones than moist foods
      (5/22). Isoflavone content and food cost were negatively correlated for dry and
      semimoist foods but not for moist foods. Total amount of isoflavone consumed by
      cats fed these soy-containing foods as a sole maintenance diet was estimated to
      be between 0.6 and 4.5 mg/kg of body weight/d, which is comparable to
      concentrations in humans that result in a measurable although modest effect on
      serum concentrations of steroid and thyroid hormones. CONCLUSIONS AND CLINICAL
      RELEVANCE: Genistein and daidzein are common constituents of commercial cat
      foods. Predictors of isoflavone content included ingredient labeling, food type,
      and food cost. Soy isoflavones in some commercial cat foods were detected in
      amounts predicted to have a biological effect.

PMID- 11843116
TI  - In vitro characterization of chondrocytes isolated from naturally occurring
      osteochondrosis lesions of the humeral head of dogs.
AB  - OBJECTIVE: To characterize chondrocytes from naturally occurring osteochondrosis
      (OC) lesions of the humeral head of dogs. SAMPLE POPULATION: 15 cartilage
      specimens from 13 client-owned dogs with humeral head OC and 10 specimens from
      the humeral head of healthy dogs (controls). PROCEDURE: Chondrocytes were
      isolated and cultured in a 3-dimensional system. On days 7, 10, 15, 20, and 25,
      glycosaminoglycan and hydroxyproline content and cytologic characteristics were
      evaluated. Expression of collagen types I, II, and X was assessed by use of
      immunohistochemistry. RESULTS: Chondrocytes from OC lesions were less viable,
      compared with control chondrocytes. Glycosaminoglycan content in the OC group was
      significantly less than in the control group on all days except day 20.
      Hydroxyproline content was also significantly less in the OC group on days 10,
      20, and 25. Expression of collagen type II was significantly less in the OC
      group, compared with the control group on all days, whereas expression of
      collagen type I was significantly greater in the OC group on days 20 and 25.
      Expression of collagen type X was significantly less in the OC group on all days
      except day 25. CONCLUSIONS AND CLINICAL RELEVANCE: Chondrocytes from naturally
      occurring OC lesions of the humeral head of dogs cultured in a 3-dimensional
      system were less viable and less capable of producing appropriate extracellular
      matrix molecules than chondrocytes from unaffected dogs. Alterations in the
      synthetic capabilities of chondrocytes from OC-affected cartilage may be a cause
      or an effect of the disease process.

PMID- 11843118
TI  - Quantitative analysis of motor unit action potentials in the subclavian muscle of
      healthy horses.
AB  - OBJECTIVE: To evaluate the application of analysis of motor unit action
      potentials (MUAP) in horses and to obtain values of MUAP for the subclavian
      muscle of horses. ANIMALS: 10 healthy adult Dutch Warmblood horses. PROCEDURE:
      Electromyographic examination of the subclavian muscle in conscious nonsedated
      horses was performed to evaluate insertional activity, spontaneous activity, MUAP
      variables, and recruitment patterns. Muscle and body temperatures were measured
      at the beginning and end of the procedure. Amplitude, duration, number of phases,
      and number of changes in direction (ie, turns) for all representative MUAP were
      analyzed to determine values for this muscle in this group of horses. RESULTS:
      Mean +/- SD duration of insertional activity was 471.7 +/- 33.45 milliseconds.
      Mean MUAP amplitude in the examined horses was 379 RV (95% confidence interval
      [CI], 349 to 410 microV). Mean MUAP duration of the subclavian muscle was 727
      milliseconds (95% CI, 6.84 to 7.71 milliseconds). Mean number of phases was 2.9,
      and mean number of turns was 3.0. Prevalence of polyphasic MUAP defined as MUAP
      with > 4 phases, was 77%. Number of MUAP that had > 5 turns was 2.4%. Satellite
      potentials were found in 1.0% of the MUAP CONCLUSIONS AND CLINICAL RELEVANCE:
      This study revealed that electromyography including MUAP analysis can be
      performed in horses, and values for the subclavian muscle in healthy adult horses
      can be obtained. Analysis of MUAP could be a valuable diagnostic tool for use in
      discriminating between myogenic and neurogenic problems in horses.

PMID- 11843117
TI  - Cloning and sequence analysis of the complementary DNA for feline
      preproparathyroid hormone.
AB  - OBJECTIVES: To clone and sequence the cDNA for feline preproparathyroid hormone
      (preproPTH) and to compare that sequence with other known parathyroid hormone
      (PTH) sequences. SAMPLE POPULATION: Parathyroid glands from 1 healthy cat.
      PROCEDURES: A cDNA library was constructed in lambda phage from feline
      parathyroid gland mRNA and screened with a radiolabeled canine PTH probe.
      Positive clones were sequenced, and nucleic acid and deduced amino acid sequences
      were analyzed and compared with known preproPTH and PTH sequences. RESULTS:
      Screening of approximately 2 X 10(5) recombinant plaques revealed 3 that
      hybridized with the canine PTH probe; 2 clones comprised the complete sequence
      for feline preproPTH. Feline preproPTH cDNA consisted of a 63-base pair (bp) 5'
      untranslated region (UTR), a 348-bp coding region, and a 326-bp 3'-UTR. The
      coding region encoded a 115-amino acid peptide. Mature feline PTH consisted of 84
      amino acids. Amino acid sequence analysis revealed that feline PTH was > 83%
      identical to canine, bovine, swine, equine, human, and macaque PTH and 69, 71,
      and 44% identical to mouse, rat, and chicken PTH, respectively. Within the region
      responsible for hormonal activity (amino acids 1 to 34), feline PTH was > 79%
      identical to other mammalian PTH sequences and 64% identical to the chicken
      sequence. CONCLUSIONS AND CLINICAL RELEVANCE: The amino acid sequence of PTH is
      conserved among mammalian species. Knowledge of the cDNA sequence for feline PTH
      may be useful to investigate disturbances of calcium metabolism and alterations
      in PTH expression in cats.

PMID- 11843119
TI  - Effects of adenosine on bacterial lipopolysaccharide- and interleukin 1-induced
      nitric oxide release from equine articular chondrocytes.
AB  - OBJECTIVE: To determine whether adenosine influences the in vitro release of
      nitric oxide (NO) from differentiated primary equine articular chondrocytes.
      SAMPLE POPULATION: Articular cartilage harvested from the metacarpophalangeal and
      metatarsophalangeal joints of 11 horses (3 to 11 years old) without history or
      clinical signs of joint disease. PROCEDURE: Chondrocytes were isolated, plated at
      a high density (10(5) cells/well), and treated with adenosine, the adenosine
      receptor agonist 5'-N-ethylcarboxamidoadenosine (NECA), bradykinin, or other
      agents that modify secondary messenger pathways alone or in combination with
      bacterial lipopolysaccharide (LPS) or recombinant human interleukin-1alpha (rhIL
      1alpha). Nitric oxide release was measured indirectly by use of the Griess
      reaction and was expressed as micromol of nitrite in the supernatant/microg of
      protein in the cell layer. Inducible nitric oxide synthase (iNOS) activity was
      determined by measuring the conversion of radiolabeled arginine to radiolabeled
      citrulline. RESULTS: Treatment of chondrocytes with adenosine alone had no
      significant effect on NO release. However, adenosine and NECA inhibited LPS- and
      rhIL-1alpha-induced NO release. This response was mimicked by forskolin, which
      acts to increase adenylate cyclase activity, but not by the calcium ionophore
      A23187 Treatment of chondrocytes with phorbol myristate acetate, which acts to
      increase protein kinase C activity, potentiated LPS-induced NO release. Adenosine
      treatment also significantly inhibited the LPS-induced increase in iNOS activity.
      CONCLUSIONS AND CLINICAL RELEVANCE: Adenosine and the nonspecific adenosine
      receptor agonist NECA inhibited inflammatory mediator-induced release of NO from
      equine articular chondrocytes. Modulation of adenosine receptor-mediated pathways
      may offer novel methods for treatment of inflammation in horses with joint
      disease.

PMID- 11843120
TI  - Use of color doppler imaging for determining the resistive index of the medial
      long posterior ciliary artery in clinically normal conscious dogs.
AB  - OBJECTIVE: To evaluate the use of color Doppler imaging (CDI) for determining the
      resistive index (RI) of the medial long posterior ciliary artery (mLPCA) in
      clinically normal conscious dogs. ANIMALS: 18 (10 sexually intact males, 8
      sexually intact females) dogs between 1 and 5 years old. PROCEDURE: Color Doppler
      ultrasonography was performed on both eyes with dogs in a sitting position. Each
      eye was imaged from the region dorsal to the zygomatic arch with the transducer
      positioned in a horizontal plane. The mLPCA was localized, and RI was calculated
      from velocities obtained for 3 similar Doppler waveforms. To determine the
      reproducibility of CDI-derived RI, measurements were repeated twice at a 10-day
      interval. RESULTS: Mean (+/- SD) RI of the mLPCA was 0.68 +/- 0.07 (95%
      confidence interval, 0.65 to 0.70; n = 36 eyes). Resistive index did not
      significantly differ between right and left eyes or male and female dogs. In
      addition, body weight was not correlated with RI. Repeated measurements of RI did
      not yield significantly different results (interclass correlation coefficient,
      0.8297). CONCLUSION AND CLINICAL RELEVANCE: Color Doppler imaging appears to be a
      valid technique for determination of RI of the mLPCA in conscious dogs. This
      technique may be useful for investigating the pathophysiologic processes of many
      ocular and orbital vascular disorders in dogs.

PMID- 11843121
TI  - Microanatomic characteristics of the insertion of the distal sesamoidean impar
      ligament and deep digital flexor tendon on the distal phalanx in healthy feet
      obtained from horses.
AB  - OBJECTIVE: To describe microanatomic characteristics of the insertion of the
      aistal sesamoidean impar ligament (DSIL) and deep digital flexor tendon (DDFT) on
      the distal phalanx in horses. SAMPLE POPULATION: Healthy feet obtained from 62
      horses of various breeds. PROCEDURE: Feet from 23 horses were used to
      histologically examine the insertion of the DSIL and DDFT (n = 7), its
      vasculature (10), and neural elements (6). In 39 other horses, the insertion zone
      was examined for proteoglycan. RESULTS: The insertion of the DSIL and dorsal half
      of the DDFT contained bundles of collagen fibers with intervening loose
      connective tissue septa with arteriovenous complexes (AVC) and nerve fibers.
      Microscopic examination revealed adaptive changes in the insertion with regard to
      proteoglycan content. In young adult horses, little or no staining for
      proteoglycans was evident, whereas in middle-aged horses, moderate proteoglycan
      staining was seen. Six older horses had slight proteoglycan staining at the
      insertion. CONCLUSIONS AND CLINICAL RELEVANCE: The study revealed that this
      region contained a rich neurovascular complex between the collagen bundles. A
      gradual increase in production of proteoglycan, evident at the insertion of the
      DSIL and DDFT on the distal phalanx, indicates that adaptive responses to stress
      rather than age alone may be the primary determining factor. These observations
      indicate that this insertion site may be susceptible to stress during stance and
      impact loading, because this region appears to be strategically situated to
      regulate important neurovascular functions of the foot.

PMID- 11843122
TI  - Evaluation of tachykinins and their receptors to determine sensory innervation in
      the dorsal hoof wall and insertion of the distal sesamoidean impar ligament and
      deep digital flexor tendon on the distal phalanx in healthy feet of horses.
AB  - OBJECTIVE: To localize substance P (SP) and neurokinin A (NKA) and their
      receptors in the insertion of the distal sesamoidean impar ligament (DSIL), deep
      digital flexor tendon (DDFT), and dorsal hoof wall of healthy feet of horses.
      SAMPLE POPULATION: 18 healthy feet from horses. PROCEDURE: Samples from the
      dorsal hoof wall and insertion of the DSIL and DDFT of 10 feet were processed for
      immunocytochemical analysis, using rabbit polyclonal antisera raised against SP
      and NKA. Tissue sections from 8 feet were incubated with 125-labeled SP to
      localize tachykinin receptors and their specificity and with control solutions of
      radioactive SP and excess nonradioactive SP to identify areas of nonspecific
      binding. RESULTS: Many nerves immunoreactive for SP and NKA were localized to the
      region of the insertion of the DSIL and DDFT and the accompanying
      microvasculature and arteriovenous complexes (AVC) as well as to the
      microvasculature of the dorsal hoof wall. Specific neurokinin 1 receptors were
      localized over the microvessels and AVC of the insertion zone and small
      microvessels of the hoof wall. CONCLUSIONS AND CLINICAL RELEVANCE: These results
      document that the microvasculature of the equine foot is richly innervated and
      has specific receptors for tachykinins. Distributions of these tachykinin
      receptors on the microvasculature suggest that they form an important
      vasodilatory mechanism for controlling blood flow through the DSILDDFT insertion
      and dorsal hoof wall.

PMID- 11843123
TI  - Isolation and measurement of carbonic anhydrase isoenzyme III in plasma, sera,
      and tissues of dogs.
AB  - OBJECTIVE: To purify canine carbonic anhydrase isoenzyme III (CA-III) and
      determine plasma, serum, and tissue concentrations of CA-III in healthy dogs and
      dogs with experimentally induced muscle damage. ANIMALS: 121 healthy Beagles.
      PROCEDURE: Muscle was obtained from 2 Beagles after euthanasia, and CA-III was
      purified and characterized by use of column chromatography and electrophoresis,
      respectively. A CA-III-specific ELISA was developed to determine concentrations
      of CA-III in plasma of 116 dogs and tissues of 1 dog. Serum creatine kinase (CK)
      activity and CA-III concentration were also determined before and after induction
      of muscle damage by IM injection of 2 ml of 10% lidocaine to 2 dogs. RESULTS:
      Canine CA-III had a molecular weight of 28 kd and an isoelectric point of 8.2.
      Mean (+/- SD) concentration of CA-III in plasma of healthy dogs was 16.91 +/-
      9.55 ng/ml. The highest tissue concentration of CA-III was detected in skeletal
      muscle. Serum concentration of CA-III increased and peaked within the first 2 to
      3 hours after induction of muscle damage. The increase in CA-III concentration
      was more rapid than that of CK activity, and concentration reached its maximum
      and returned to baseline sooner than did CK activity. CONCLUSIONS AND CLINICAL
      RELEVANCE: The CA-III ELISA we developed was a sensitive method for determining
      CA-III concentrations in plasma, serum samples, and tissue specimens of dogs. Use
      of this ELISA requires only a small volume of serum and may enable the study of
      changes in CA isoenzyme concentrations associated with muscle disorders in dogs.

PMID- 11843124
TI  - Apoptosis and oxidative stress of infiltrated neutrophils obtained from mammary
      glands of goats during various stages of lactation.
AB  - OBJECTIVE: To examine apoptosis in infiltrated neutrophils during involution of
      mammary glands and compare them with those obtained during late and peak
      lactation, and to measure oxidative stress and activities of antioxidant enzymes
      and determine involvement of free radicals in apoptosis of infiltrated
      neutrophils. SAMPLE POPULATION: Neutrophils from mammary gland secretions of 8
      goats at 4 stages (late and peak lactation and 1 and 2 weeks after end of
      lactation). PROCEDURE: DNA fragmentation was evaluated to characterize apoptosis.
      Concentration of thiobarbituric acid reactive substances (TBARS) was used to
      evaluate oxidative stress. Activities of superoxide dismutase and glutathione
      peroxidase were determined. RESULTS: Neutrophils from secretions obtained after
      end of lactation of all goats and from late-lactation milk of some goats
      underwent prominent apoptosis, whereas neutrophils from peak lactation secretions
      did not. Higher lipid peroxidation and lower antioxidant enzyme activities in
      neutrophils during involution were observed, compared with those during late and
      peak lactation. A significant negative correlation existed between TBARS
      concentrations and antioxidant enzyme activities during the nonlactating period.
      CONCLUSIONS AND CLINICAL RELEVANCE: Apoptosis is a feature of infiltrated
      neutrophils during involution of mammary glands in goats. This feature may allow
      prompt resorption and clearance of infiltrated neutrophils without damaging
      surrounding tissues. Increased oxidative stress in infiltrated neutrophils from
      secretions obtained after end of lactation is probably related to a deficiency in
      antioxidant enzyme activities. Understanding the relationship between apoptosis
      and oxidative stress will lead to new strategies for manipulating involution and
      reducing tissue damage.

PMID- 11843125
TI  - Evaluation of a lateral-flow immunoassay for use in monitoring passive transfer
      of immunoglobulins in calves.
AB  - OBJECTIVE: To determine the predictive ability of a commercially available
      lateral-flow immunoassay used for determining passive transfer of immunoglobulins
      in calves. ANIMALS: 204 male Holstein calves ranging from 4 to 8 days old.
      PROCEDURE: Serum samples were obtained from each calf. Results of refractometry,
      zinc sulfate turbidity technique, and the lateral-flow immunoassay were
      determined. Sensitivity, specificity, accuracy, and predictive ability were
      calculated on the basis of IgG concentrations determined by turbidimetric
      immunoassay (TIA). RESULTS: Mean IgG concentration in the study was 10.9 mg/ml as
      determined by TIA. Rate of failure of passive transfer in this study population
      was 56%. Associations between the values for the refractometry and zinc sulfate
      turbidity techniques were established by regression analysis. Accuracy for the
      lateral-flow immunoassay, refractometry, and zinc sulfate turbidity methods was
      95, 80, and 73%, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: The lateral
      flow immunoassay was better at determining the status of passive transfer of
      immunoglobulins, compared with the refractometry or zinc sulfate turbidity
      methods. The ability of the lateral-flow immunoassay to provide accurate results
      should enable clinicians to make immediate management or intervention decisions.

PMID- 11843126
TI  - Effects of vaccination prior to transit and administration of florfenicol at time
      of arrival in a feedlot on the health of transported calves and detection of
      Mannheimia haemolytica in nasal secretions.
AB  - OBJECTIVE: To determine effects of vaccination prior to transit and prophylactic
      administration of florfenicol at time of arrival at a feedyard on health of
      cattle and colonization of the nasopharynx by Mannheimia haemolytica (MH).
      ANIMALS: 121 steers from Tennessee and 84 steers from New Mexico. PROCEDURE: Half
      of the steers were vaccinated before transport to a feedyard. Steers from
      Tennessee were vaccinated with MH bacterin-toxoid, and steers from New Mexico
      were vaccinated intranasally with modified-live leukotoxin-deficient MH. Half of
      the vaccinates and nonvaccinates were randomly selected to receive florfenicol on
      arrival at the feedyard. Steers were observed daily for respiratory tract disease
      (RTD). RESULTS: Administration of florfenicol at time of arrival reduced the
      incidence of RTD, delayed the interval before onset of RTD, and reduced the
      incidence of MH colonization of the nasopharynx for at least 4 days, but
      vaccination did not have any effect. Vaccination elicited an increase in serum
      antibody titers to MH. Administration of florfenicol at time of arrival reduced
      the development of serum antibody titers in intranasally vaccinated steers and
      both groups of nonvaccinated steers, but intranasal vaccination did not affect
      colonization by wild-type MH. CONCLUSIONS AND CLINICAL RELEVANCE: Administration
      of florfenicol at time of arrival decreased the incidence of MH organisms in the
      nasopharynx and delayed the onset of RTD. Prophylactic use of suitable
      antibiotics is likely to reduce the incidence of acute RTD in calves for several
      days after arrival at feedyards, which is the period when they are most
      susceptible to infectious organisms.

PMID- 11843127
TI  - Morphologic features of degeneration and cell death in the neurosensory retina in
      dogs with primary angle-closure glaucoma.
AB  - OBJECTIVE: To investigate cellular death in the neurosensory portion of the
      retina during the first 7 days after onset of clinical signs of overt primary
      angleclosure glaucoma (PACG) in dogs. SAMPLE POPULATION: 14 globes from dogs with
      PACG and 2 normotensive globes from dogs with PACG in the opposite eye.
      PROCEDURES: Retinas were examined via light microscopy and terminal
      deoxynucleotidyl transferase-mediated biotin-dUTP nick end-labeling. RESULTS:
      Necrosis of ganglion cells and segmental degeneration of the nerve fiber layer
      rapidly progressed to scattered full-thickness retinal attenuation and
      disorganization. Apoptosis was detectable within 1 day after onset of PACG and
      was prominent by 3 days. Necrosis of ganglion cells was significantly greater in
      retinas affected for < or = 1 day, compared with retinas affected for > 1 day. In
      contrast, apoptosis in the ganglion cell layer was significantly greater in
      retinas affected for > 1 day, compared with retinas affected for < or = 1 day.
      End-stage retinal atrophy was seen by day 7. CONCLUSIONS AND CLINICAL RELEVANCE:
      The presence of necrotic ganglion cells within 1 day after onset of clinical
      signs suggests a narrow window of opportunity to initiate effective therapy in
      overt PACG. Photoreceptor death is an important and striking aspect of
      neurosensory retinal degeneration after acute onset of PACG.

PMID- 11843128
TI  - Prevalence and characteristics of attaching and effacing strains of Escherichia
      coli isolated from diarrheic and healthy sheep and goats.
AB  - OBJECTIVE: To determine the prevalence and characteristics of attaching and
      effacing Escherichia coli (AEEC) in diarrheic and healthy small ruminants.
      ANIMALS: 502 lambs and kids with diarrhea and 511 healthy sheep and goats.
      PROCEDURE: Fecal samples from diarrheic and healthy sheep and goats were screened
      for the eae gene. In addition, E coli isolates with positive results for the eae
      gene (E coli eae+) were analyzed for the espB gene, production of verotoxins
      (VT), and serogroup. RESULTS: A significantly higher prevalence of healthy lambs
      and kids were infected with AEEC, compared with diarrheic lambs and kids and
      healthy adult sheep and goats. Some differences in the characteristics of E coli
      eae strains isolated from diarrheic and healthy animals were detected. Thus, the
      espB gene was detected more frequently among E coli eae+ strains isolated from
      healthy animals than in those isolated from diarrheic animals, and VT production
      was only detected in E coli eae+ strains isolated from healthy lambs and kids.
      The E coli eae+ isolates belonged to several O serogroups. However, 17 of 40
      (42.5%) isolates from diarrheic lambs and only 4 of 168 (2.4%) isolates from
      healthy sheep belonged to serogroup 026. CONCLUSIONS AND CLINICAL RELEVANCE: Our
      results suggest that E coli eae+ 026 strains may play a role in diarrheal disease
      in lambs, whereas E coli eae+ strains that also had VT production and eae+
      strains that had positive results for the espB gene did not appear to be
      associated with diarrhea in small ruminants.

PMID- 11843129
TI  - Use of an extracorporeal circuit to evaluate effects of intraluminal distention
      and decompression on the equine jejunum.
AB  - OBJECTIVE: To use an extracorporeal circuit to evaluate effects of intraluminal
      distention on the jejunum of healthy horses. SAMPLE POPULATION: 2 jejunal
      segments from each of 5 horses. PROCEDURE: Jejunal segments were harvested and
      maintained in an extracorporeal circuit. One segment was subjected to distention
      (intraluminal pressure, 25 cm H2O) followed by decompression, and 1 segment was
      maintained without distention. The influence of distention-decompression on
      vascular resistance was calculated. Mucosal permeability was evaluated by
      measuring the clearance of albumin from blood to lumen. After distention and
      decompression, tissue specimens were collected for histomorphologic evaluation.
      In addition, the contractile response of the circular smooth muscle layer was
      determined following incubation with 3 prokinetic agents. RESULTS: Intestinal
      vascular resistance increased during intraluminal distention and returned to
      baseline values after decompression. Albumin clearance rate increased after
      distention, compared with baseline and control values. Histologic examination of
      the distended segments revealed grade-1 and -2 lesions of the mucosal villus.
      Edema and hemorrhage were evident in the submucosa and muscular layers.
      Mesothelial cell loss, edema, and hemorrhage were also evident in the serosa.
      Mucosal surface area and villus tip height decreased and submucosal volume
      increased in the distended tissue. Compared with responses in control specimens,
      distention decreased the contractile response induced by cisapride, erythromycin,
      and metoclopramide. CONCLUSIONS AND CLINICAL RELEVANCE: Intraluminal distention
      of the jejunum followed by decompression increased mucosal permeability and
      injury and decreased responses to prokinetic agents. Horses with intraluminal
      intestinal distention may have a decreased response to prokinetic agents.

PMID- 11843130
TI  - Effects of immobilization followed by remobilization on mineral density,
      histomorphometric features, and formation of the bones of the metacarpophalangeal
      joint in horses.
AB  - OBJECTIVE: To determine microradiographic appearance, bone histomorphometry, and
      mineral density of the long bones of the metacarpophalangeal joint in horses
      after immobilization followed by remobilization. ANIMALS: 5 healthy horses.
      PROCEDURE: One forelimb of each horse was immobilized in a fiberglass cast for 7
      weeks, followed by 8 weeks of increasing exercise. Calcein and oxytetracycline
      were administered IV during the immobilization and exercise phases, respectively,
      for bone labeling and analysis after euthanasia. Sagittal sections of metacarpal
      bones and proximal phalanges were examined via radiography, dual energy x-ray
      absorptiometry, histomorphometry, and bone label analysis. RESULTS: Radiography
      revealed loss of bone mineral opacity in the subarticular regions of the
      immobilized metacarpal bones and phalanges and subchondral lesions in metacarpal
      bones in 2 horses. In phalanges, a significant decrease in subarticular
      volumetric bone mineral density was detected. There was significantly less bone
      volume and calcein-labeled bone surface and more vascular volume and
      oxytetracycline-labeled bone surface in immobilized phalanges, compared with
      contralateral phalanges. CONCLUSIONS AND CLINICAL RELEVANCE: Eight weeks of
      exercise after single-limb immobilization is insufficient for recovery of
      volumetric bone mineral density. During immobilization and remobilization, the
      subchondral and trabecular bone appear to be actively remodeling.

PMID- 11843131
TI  - Clinical evaluation of the effects of immobilization followed by remobilization
      and exercise on the metacarpophalangeal joint in horses.
AB  - OBJECTIVES: To evaluate clinical effects of immobilization followed by
      remobilization and exercise on the metacarpophalangeal joint (MPJ) in horses.
      ANIMALS: 5 healthy horses. PROCEDURE: After lameness, radiographic, and force
      plate examinations to determine musculoskeletal health, 1 forelimb of each horse
      was immobilized in a fiberglass cast for 7 weeks, followed by cast removal and
      increasing amounts of exercise, beginning with hand-walking and ending with
      treadmill exercise. Lameness examination, arthrocentesis of both MPJ, single
      emulsion radiographic examination, nuclear scintigraphic examination, ground
      reaction force-plate analysis, and computed tomographic examination were done at
      various times during the study. RESULTS: All horses were lame in the immobilized
      MPJ after cast removal; lameness improved slightly with exercise. Force plate
      analysis revealed a significant difference in peak forces between immobilized and
      contralateral limbs 2 weeks after cast removal. Range of motion of the
      immobilized MPJ was significantly decreased, and joint circumference was
      significantly increased, compared with baseline values, during the exercise
      period. Osteopenia was subjectively detected in the immobilized limbs.
      Significant increase in the uptake of radionucleotide within bones of the
      immobilized MPJ after cast removal and at the end of the study were detected.
      Loss of mineral opacity, increased vascular channels in the subchondral bone, and
      thickening within the soft tissues of the immobilized MPJ were detected.
      CONCLUSIONS AND CLINICAL RELEVANCE: Results indicate that 8 weeks of enforced
      exercise after 7 weeks of joint immobilization did not restore joint function or
      values for various joint measurements determined prior to immobilization.

PMID- 11843132
TI  - Evaluation of laparoscopic adhesiolysis for the treatment of experimentally
      induced adhesions in pony foals.
AB  - OBJECTIVE: To assess the efficacy of laparoscopic adhesiolysis in the treatment
      of experimentally induced adhesions in foals. ANIMALS: 8 healthy pony foals.
      PROCEDURE: Celiotomy was performed and adhesions created at the jejunoileal
      junction and at sites 0.5 and 1 m proximal to this junction, using a serosal
      abrasion method. Ten days after celiotomy, exploratory laparoscopy was performed.
      Laparoscopic adhesiolysis was performed in the treatment group only (4 foals,
      randomly selected). Thirty days after the exploratory laparoscopy, a final
      laparoscopic examination was performed, and the foals were euthanatized. The
      number and characteristics of abdominal adhesions were recorded during
      laparoscopy 10 and 30 days after celiotomy and during necropsy. RESULTS: At 30
      days after celiotomy, the number of adhesions in the control group was
      significantly higher than the number in the treatment group. In the control
      group, all adhesions observed during the exploratory laparoscopy were still
      evident at the final laparoscopy and necropsy. In the treatment group, adhesions
      did not form again after separation. During final laparoscopy and necropsy, a
      focal adhesion between the omentum and site of the initial laparoscope portal was
      observed in 5 of 8 foals. CONCLUSIONS AND CLINICAL RELEVANCE: The serosal
      abrasion model is useful for studying abdominal adhesions in foals. Laparoscopic
      adhesiolysis was an effective technique to break down experimentally induced
      adhesions in the early maturation stage of formation in pony foals. Studies are
      required to investigate prevention of de novo adhesions at the laparoscope portal
      sites.

PMID- 11843133
TI  - Effect of short-chain fatty acids on contraction of smooth muscle in the canine
      colon.
AB  - OBJECTIVE: To determine effects of short-chain fatty acids (SCFA) on canine
      colonic smooth muscle. SAMPLE POPULATION: Colonic tissue obtained from 14 healthy
      dogs. PROCEDURE: Short-chain fatty acid (SCFA; acetate, propionate, and butyrate;
      1 to 100 mmol/L)-induced contractions were compared with responses obtained with
      acetylmethylcholine (AMCh; 10(-4) mol/L). Roles of enteric neurons, cholinergic
      receptors, calcium stores in the sarcoplasmic reticulum, and extracellular
      calcium in the SCFA-induced responses were investigated by incubating muscle
      strips with tetrodotoxin (1 micromol/L), atropine (1 micromol/L), ryanodine (10
      micromol/L), nifedipine (1 micromol/L), ethylene glycol-bis (beta
      aminoethylether)-N,N,N',N'-tetra-acetate (EGTA; 0.1 mmol/L), or an extracellular
      calcium-depleted (zero extracellular calcium) solution prior to the addition of
      propionate or butyrate. RESULTS: Incubation with SCFA elicited isometric stress
      responses (0.25 to 2.15 x 10(4) N/m2) in colonic longitudinal smooth muscle.
      Maximal responses to butyrate and propionate (50 mmol/L) were 37 and 23%,
      respectively, of the maximal AMCh response. Acetate was least effective in
      stimulating contractile responses. Tetrodotoxin and atropine did not affect SCFA
      induced contractions. Nifedipine and zero extracellular calcium solution
      abolished responses to butyrate and propionate, whereas EGTA attenuated (> 60%)
      but did not abolish those responses. Ryanodine did not affect SCFA-induced
      contractile responses. The SCFA did not affect colonic circular smooth muscle.
      CONCLUSIONS AND CLINICAL RESPONSE: The SCFA stimulate longitudinal but not
      circular colonic smooth muscle contractions via a direct effect on smooth muscle.
      The mechanism of the SCFA effect appears to involve the influx of extracellular
      calcium. These findings may account for some of the effects of fiber on canine
      colonic motility [corrected].

PMID- 11843135
TI  - Inactivation of infectious salmon anaemia virus, viral haemorrhagic septicaemia
      virus and infectious pancreatic necrosis virus in water using UVC irradiation.
AB  - The UVC irradiation doses necessary for a 99.9% (3-log) inactivation of 3
      different fish pathogenic viruses diluted in freshwater/seawater and wastewater
      from a fish processing plant were determined. The results showed that both
      infectious salmon anaemia virus (ISAV) and viral haemorrhagic septicaemia virus
      (VHSV) were very sensitive to UVC irradiation, showing a 3-log reduction of
      infectivity in freshwater of 33 +/- 3.5 and 7.9 +/- 1.5 J m(-2), respectively,
      while that of infectious pancreatic necrosis virus (IPNV) was substantially
      higher, 1188 +/- 57 J m(-2). Using ISAV as a model, a comparison of the effect of
      UVC irradiation on virus isolation versus reverse transcription polymerase chain
      reaction (RT-PCR) showed that considerably higher UVC doses, depending on the
      length of the amplified product, were necessary to abolish RT-PCR detection of
      viral RNA.

PMID- 11843134
TI  - Phenotypic expression of equine articular chondrocytes grown in three-dimensional
      cultures supplemented with supraphysiologic concentrations of insulin-like growth
      factor-1.
AB  - OBJECTIVE: To assess the effects of supraphysiologic concentrations of insulin
      like growth factor-1 (IGF-1) on morphologic and phenotypic responses of
      chondrocytes. SAMPLE POPULATION: Articular cartilage obtained from 2 young
      horses. PROCEDURE: Chondrocytes were suspended in fibrin cultures and
      supplemented with 25, 12.5, or 0 mg of IGF-1/ml of fibrin. Chondrocyte morphology
      and phenotypic expression were assessed histologically, using H&E and Alcian blue
      stains, immunoreaction to collagen type I and II, and in situ hybridization.
      Proteoglycan content, synthesis, and monomer size were analyzed. The DNA content
      was determined by bisbenzimide-fluorometric assay, and elution of IGF-1 into
      medium was determined by IGF-1 radioimmunoassay. RESULTS: Both 12.5 and 25 kg of
      IGF-1/ml enhanced phenotypic expression of chondrocytes without inducing
      detrimental cellular or metabolic effects. Highest concentration of IGF-1 (25
      microg/ml) significantly increased total DNA content, glycosaminoglycan (GAG)
      content, GAG synthesis, and size of proteoglycan monomers produced, compared with
      cultures supplemented with 12.5 microg of IGF-1/ml or untreated cultures.
      Histologic examination confirmed these biochemical effects. Matrix metachromasia,
      type-II collagen in situ hybridization and immunoreaction were increased in
      cultures treated with 25 microg of IGF-1/ml, compared with cultures supplemented
      with 12.5 microg of IGF-1/ml or untreated cultures. CONCLUSIONS AND CLINICAL
      RELEVANCE: Chondrocytes exposed to high concentrations of IGF-1 maintained
      differentiated chondrocyte morphology and had enhanced synthesis of matrix
      molecules without inducing apparent detrimental effects on chondrocyte
      metabolism. These results suggest that application of such composites for in vivo
      use during cartilage grafting procedures should provide an anabolic effect on the
      grafted cells.

PMID- 11843136
TI  - Iridovirus infections in farm-reared tropical ornamental fish.
AB  - A systemic viral infection in both gourami Trichogaster spp. and swordtail
      Xiphophorus hellerii and an outbreak of lymphocystis in scalare Pterophyllum
      scalarae and gourami are reported to have occurred in fish reared in ornamental
      fish farms in Israel. The systemic infection developed in endothelial cells that
      became hypertrophic and their contents were modified. The presence of such cells
      in light-microscopically examined stained smears and sections provides an initial
      indication for this systemic viral infection. Infection in gourami caused
      hemorrhagic dropsy. Transmission electron microscopic (TEM) images of iridovirus
      like particles recovered from gouramies showed them to be 138 to 201 nm from
      vertex to vertex (v-v); those from swordtails were 170 to 188 nm v-v. TEM images
      of lymphocystis virions from scalare were 312 to 342 nm v-v and from gourami 292
      to 341 nm v-v. Lymphocystis cells from the gourami were joined by a solid hyaline
      plate, which was lacking in the infection in scalare where the intercellular
      spaces between the lymphocystis cells consisted of loose connective tissue.

PMID- 11843137
TI  - Characterization of an iridovirus from the cultured pig frog Rana grylio with
      lethal syndrome.
AB  - Three virus isolates, RGV-9506, RGV-9807 and RGV-9808, were obtained from
      cultured pig frogs Rana grylio undergoing lethal infections. Previously, the
      first isolate, RGV-9506, was shown to be an iridovirus based on ultrastructural
      and morphological studies. In the present study, the original isolate, along with
      2 recent ones, were more extensively characterized by experimental infection
      studies, histopathology, electron microscopy, serological reactivity, gel
      electrophoresis of viral polypeptides and DNA restriction fragments, PCR
      amplification, and nucleic acid sequence analysis of the major capsid protein
      (MCP) gene. The 3 isolates were shown to be identical to each other, and very
      similar to FV3, the type species of the genus Ranavirus (family Iridoviridae).
      These results suggest that RGV should be considered a strain of FV3, and indicate
      that FV3-like iridoviruses are capable of causing widespread, severe disease
      among cultured frogs.

PMID- 11843138
TI  - Portals of entry and systemic localization of proliferative gill disease
      organisms in channel catfish Ictalurus punctatus.
AB  - Immunized rabbit serum adsorbed in live catfish was used in indirect fluorescent
      antibody test (IFAT) to detect developmental life stages of Henneguya ictaluri n.
      sp. This myxozoan parasite is associated with proliferative gill disease in
      channel catfish Ictalurus punctatus (Rafinesque) in the USA. Specific pathogen
      free fingerlings were experimentally infected with the actinosporean stage of H.
      ictaluri and necropsied 24, 48, 72, and 96 h post-infection. At 24 h post
      infection parasite stages were observed primarily in the gastric mucosa and
      submucosa but were also observed in the skin and buccal cavity. Ovoid organisms
      were detected in heart and blood vessels of the liver. From 48 to 72 h after
      exposure, fewer fluorescent organisms were located in all organs, with the
      exception of the gills, than were observed at 24 h. These organisms appeared to
      be degenerating except for those in the gills, which appeared to be
      multinucleated. By 96 h post-infection, the organisms could not be detected in
      fish tissues with the exception of the stages in the gills, which appeared to be
      a preferred site of development. Throughout the entire 96 h period of study, no
      stage of the organism was detected in the brain. Infected tissue sections treated
      with non-immune rabbit serum and non-infected tissue sections treated with immune
      rabbit sera all showed negative results by IFAT.

PMID- 11843139
TI  - Effect of temperature and salinity on in vitro zoosporulation of Perkinsus sp. in
      Manila clams Ruditapes philippinarum.
AB  - The effects of temperature and salinity on in vitro development of Perkinsus sp.
      prezoosporangia isolated from cultured Manila clams in Korea were investigated,
      and the difference in resistance to low temperature between prezoosporangia
      collected in winter and those collected in summer was compared. Temperature and
      salinity had significant effects on the development of prezoosporangia, and the
      developmental rates increased with increasing temperature and salinity.
      Prezoosporangia isolated in winter sporulated and released motile zoospores at 10
      degrees C, although the rates were significantly lower than those at 20 and 30
      degrees C. However, no prezoosporangia collected in summer sporulated at 10
      degrees C. Low salinities (< or = 10/1000) had a significant negative effect on
      the development of prezoosporangia. A small number of prezoosporangia sampled in
      summer did sporulate at 5/1000, but further developments including formation and
      release of zoospores were not observed. However, prezoosporangia sampled in
      winter and incubated at 5/1000 released motile zoospores, although the rates were
      significantly lower than those at higher salinities.

PMID- 11843140
TI  - Mantle-shell complex reactions elicited by digenean metacercariae in Gaimardia
      trapesina (Bivalvia: Gaimardiidae) from the Southwestern Atlantic Ocean and
      Magellan Strait.
AB  - The host response to 3 different larval digeneans affecting Southwestern Atlantic
      and Magellanic populations of the bivalve Gaimardia trapesina (Lamarck, 1819)
      (Gaimardiidae) is described. Unencysted metacercariae of 2 species of
      Gymnophallidae and 1 species of Lepocreadiidae co-exist in the peripheral and
      general extrapallial spaces. Differences in host responses to stimuli generated
      by each parasite are described. Infections by Gymnophallidae gen. sp. 1
      metacercariae elicit a mantle-shell complex reaction involving both alteration of
      the mantle epithelium (hyperplasia and metaplasia) and calcium carbonate
      deposition to form an incomplete calcareous covering of single larvae, comprising
      individual crystallites in an organic matrix. The calcareous covering covers only
      the posterior two-thirds of the larval body, having its anterior end free in the
      extrapallial space, which ensures survival of the larvae. The peculiar features
      of the host response result from a successful process of adjustment to the
      parasite's life cycle. Metacercariae of Gymnophallidae gen. sp. 2 occur in one or
      more small groups of up to 30 individuals, either in the general or in the
      peripheral extrapallial spaces. The outer mantle reaction includes hyperplasia
      and metaplasia of the epithelium adjacent to the larvae. Deposition of calcium
      carbonate did not occur. Lepocreadiidae gen. sp. metacercariae were observed
      exclusively in the general extrapallial space lodged in single shallow pits whose
      shape fit the parasite's body shape and size. In simultaneous infections,
      metacercariae of Gymnophallidae and Lepocreadiidae elicited different responses
      in an individual, which suggests that each parasitic entity involves a different
      stimulus to the host.

PMID- 11843141
TI  - Diseases, prophylaxis and treatment of the Atlantic halibut Hippoglossus
      hippoglossus: a review.
AB  - After substantial investments in research, the Atlantic halibut Hippoglossus
      hippoglossus is now being cultivated commercially in Norway, Iceland, Scotland
      and Canada. As with other domesticated species, disease problems have been
      experienced. This review summarizes the current state of knowledge of diseases of
      the Atlantic halibut, and their diagnosis, prophylaxis and treatment. In economic
      terms, the most important losses have been suffered at the larval and juvenile
      stages. The most important infections are caused by nodaviruses, causative agents
      of Viral Encephalopathy and Retinopathy (VER), which are the major reason why
      Norway's production of halibut fry has been level since 1995. An aquatic
      birnavirus, Infectious Pancreatic Necrosis Virus, is also an important agent of
      mortality. Vibrio anguillarum, Flexibacter ovolyticus and atypical Aeromonas
      salmonicida are the major bacterial pathogens. The protozoan parasites recorded
      include Ichthyobodo sp., the microsporidium Enterocytozoon sp., Trichodina
      hippoglossi, and the metazoan pathogens include myxozoans, helminths, Entobdella
      hippoglossi, Lepeophtheirus hippoglossi and other parasitic copepods.
      Experimental vaccines have been tested against V anguillarum and atypical A.
      salmonicida, with good results. A recombinant vaccine against nodaviruses is
      under development. A few trials have been carried out on non-specific
      immunostimulants, but no such treatment is currently available. A number of
      efficacy and pharmacokinetic trials with various antibacterial agents have also
      been published.

PMID- 11843143
TI  - Accumulation of the lipophilic environmental contaminant lindane in metacercariae
      of Bucephaloides gracilescens (Trematoda, Bucephalidae) in the central nervous
      system of bullrout Myoxocephalus scorpius.
AB  - Bucephaloides gracilescens is a common parasite in the intestine of the angler
      fish Lophiuspiscatorius, and the metacercariae have been recorded from a number
      of gadoid intermediate hosts. In a toxicokinetic study of lindane (gamma
      hexachlorocyclohexane) in bullrout Myoxocephalus scorpius, metacercariae of B.
      gracilescens were found in the central nervous system (CNS). Furthermore, the
      metacercariae accumulated concentrations of lindane that were higher than in the
      surrounding CNS tissue. This is the first report of metacercariae of B.
      gracilescens in bullrout. In addition the present results contribute knowledge of
      the disposition of an important environmental contaminant in the metacercarial
      stage of a trematode that has been pointed out as a promising sentinel species of
      pollution in the marine environment.

PMID- 11843144
TI  - Green chemical approaches toward high-quality semiconductor nanocrystals.
AB  - Green chemistry principles have gradually been implemented into the development
      of the synthetic chemistry of high-quality semiconductor nanocrystals. In
      comparison with the original organometallic approach, the resulting alternative
      routes are safe, simple, inexpensive, reproducible, versatile, "user friendly",
      and yield nanocrystals with well-controlled size, shape, and size/shape
      distribution. Further developments in this direction will promote the
      understanding of crystallization in general.

PMID- 11843142
TI  - Isolation and characterisation of rhabdovirus from wild common bream Abramis
      brama, roach Rutilus rutilus, farmed brown trout Salmo trutta and rainbow trout
      Oncorhynchus mykiss in Northern Ireland.
AB  - Rhabdovirus was isolated from wild common bream Abramis brama during a disease
      outbreak with high mortality in Northern Ireland during May 1998. Rhabdovirus was
      also isolated at the same time from healthy farmed rainbow Oncorhynchus mykiss
      and brown trout Salmo trutta on the same stretch of river and 11 mo later from
      healthy wild bream and roach Rutilus rutilus in the same river system.
      Experimental intra-peritoneal infection of bream and mirror carp Cyprinus carpio
      var specularis with 2 of these isolates produced low mortality rates of < or =
      12%. Serological testing of these isolates by virus neutralisation indicated that
      they were antigenically closely related to pike fry rhabdovirus (PFRV) but not to
      spring viraemia of carp virus (SVCV), while testing by enzyme-linked
      immunosorbent assay indicated them to be antigenically different from both.
      Comparison of nucleotide sequence data of a 550 base pair segment of the viral
      glycoprotein generated by reverse transcription-polymerase chain reaction
      indicated a high (> or = 96.6%) degree of similarity between these isolates and a
      previous Northern Ireland isolate made in 1984, a 1997 isolate from bream in the
      Republic of Ireland and an earlier Dutch isolate from roach. In contrast,
      similarity between these isolates and PFRV was < 82.4%, indicating that these
      viruses belong to 2 distinct genogroups, while similarity to SVCV was even lower
      (< 67.4%).

PMID- 11843145
TI  - Inorganic radicals in organic synthesis.
AB  - Inorganic radicals have so far led a shadowy existence in synthetic organic
      radical chemistry. This article briefly reviews the synthetic applications of the
      most important inorganic radicals. In addition, a new synthetic concept is
      presented, which should demonstrate that with inorganic, oxygen-centered radicals
      of the type X-O*, in which X is NO2, SO3-, and H, respectively, novel oxidative
      radical reactions could be performed, which in turn are difficult or impossible
      with their organic counterparts, the alkoxyl radicals R-O*.

PMID- 11843146
TI  - Synthesis, X-ray and neutron diffraction characterization, and ionic conduction
      properties of a new oxothiomolybdate Li3[Mo8S8O8(OH)8[HWO5(H2O)]] x 18H2O.
AB  - The new oxothiomolybdate anion [Mo8S8O8(OH)8[HWO5(H2O)]]3- (denoted HMo8W3-) has
      been synthesized in aqueous solution by an acido-basic condensation reaction.
      Four (Mo(V)2S2O2) building blocks are connected through hydroxo bridges around a
      central [W(VI)O6] octahedron. X-ray and neutron diffraction studies have been
      performed on single crystals of the lithium salt Li3[Mo8S8O8(OH)8[HWO5(H2O)]] x
      18H2O (Li3HMo8W x 18H2O) in an aqueous grown from HMo8W3- solution of LiCl (1 M).
      The neutron diffraction experiment enabled us to locate both the protons and the
      lithium ions. In the structure of Li3HMo8W x 18H20, ring-shaped anions
      interleaved by a cluster of disordered hydrogen-bonded water molecules stack on
      top of each other along lithium pillars. The lithium columns are formed by
      alternating edge-sharing octahedra and tetrahedra, with one lithium site in four
      being totally vacant. Ionic conductivity measurements on pressed pellets have
      shown that Li3HMo8W x 18H2O is a good ionic conductor at room temperature (sigma
      = 10(-5) S cm(-1)), but the ionic conductivity on single crystals is smaller by
      two orders of magnitude and is isotropic; this suggests the main path of
      conduction involves surface protons rather than lithium ions of the bulk.

PMID- 11843147
TI  - Phenylacetylene macrocycles with two opposing bipyridine donor sites: syntheses,
      X-ray structure determinations, and Ru complexation.
AB  - Reaction of the known macrocycle 1a, which contains two bipyridine units in
      opposing sides, with two equivalents of [Ru(bipy)2Cl2] furnishes the doubly
      exocyclically complexed macrocycle 8a in 55% yield. Synthesis of the shape
      persistent macrocycle 1c by Hagihara-Sonogashira cross-coupling chemistry of
      suitably functionalized building blocks is reported. This macrocycle was also
      converted into a Ru complex (8c). X-ray analysis of single crystals of 1b and 1c
      shows a layered structure that contains "channels" filled with solvent molecules
      and parts of the flexible chains, with which the cycle is decorated for
      solubility reasons.

PMID- 11843148
TI  - Polybenzimidazole-supported [Rh(cod)Cl]2 complex: effective catalyst for the
      polymerization of substituted acetylenes.
AB  - The first heterogeneous catalyst which affords polymerization of substituted
      acetylenes into readily available high molecular weight polymers is reported. The
      catalyst (Rh/PBI) has been prepared by supporting di-mu-chloro-bis(eta4-cycloocta
      1,5-diene)dirhodium(I), [Rh(cod)Cl]2, on commercial polybenzimidazole (PBI)
      porous beads by means of a simple quantitative adsorption from THF solution, and
      tested in polymerization of phenylacetylene, 4-fluorophenylacetylene, and 4
      pentylphenylacetylene. The polymer molecules formed were found to be released
      from the Rh/PBI to surrounding solution during the polymerization performed in
      THF. Formation of high molecular weight ((M)w values up to 325,000) polymers in
      prevailing cis-transoid configuration has been observed with all monomers. In a
      comparison with free [Rh(cod)Cl]2 used as the homogeneous catalyst, the Rh/PBI
      can be used repeatedly, exhibits somewhat lower polymerization activity but
      almost no oligomerization activity, and provides polymers of higher molecular
      weight.

PMID- 11843149
TI  - Stepwise formation of quasi-octahedral macrocyclic complexes of rhodium(III) and
      iridium(III) bearing a pentamethylcyclopentadienyl group.
AB  - Reactions of [[MCl2(Cp*)]2] (1: M=Ir, 2: M=Rh) with bidentate ligands (L) such as
      1,4-diisocyano-2,5-dimethylbenzene (a), 1,4-diisocyano-2,3,5,6-tetramethylbenzene
      (b), pyrazine (c) or 4,4'-dipyridyl (d) gave the corresponding dinuclear
      complexes [[MCl2(Cp*)]2(L)] (M=Ir: 3a, 3b, 5c, 5d; M=Rh: 4b, 6c, 6d), which were
      converted into tetranuclear complexes [[M2(mu-Cl)2(Cp*)2]2(L)2](OTf)4 (M=Ir: 7c,
      7d, 9a, 9b; M=Rh: 8e, 8d, 10b) on treatment with Ag(OTf). X-ray analyses of 8c
      and 8d revealed that each of four pentamethylcyclopentadienyl metal moieties was
      connected by two mu-Cl-bridged atoms and a bidentate ligand to construct a
      rectangular cavity with the dimensions of 3.7 x 7.0 A for 8c and 3.7 x 11.5 A for
      8d. Both the Rh2Cl2 and pyrazine (or 4,4'dipyridyl) ring planes are perpendicular
      to the Rh4 plane. Treatment of Cl-bridged complexes (7c, 7d, 8e, 8d, 9b, and 10b)
      with a different ligand (L') resulted in cleavage of the Cl bridges to produce
      two-dimensional complexes [[MCl(Cp*)]4[(L)-(L')]2](OTf)4 (11ac, 11bc, 11bd, 12bc,
      and 12bd) with two different ligand "edges". Complex 10b reacted readily with 1,4
      diisocyano-2,3,5,6-tetramethylbenzene (b) to give a tetranuclear rhodium(III)
      complex 12bb. The structure of tetranuclear complexes was confirmed by X-ray
      analysis of 11bc. Each [MCp*] moiety is surrounded by a Cl atom, isocyanide, and
      pyrazine (or 4,4'-dipyridyl) and the dimensions of its cavity are 7.0 x 11.6 A.

PMID- 11843151
TI  - Metal-induced B-H activation: addition of acetylene, propyne, or 3-methoxypropyne
      to Rh(Cp*), Ir(Cp*), Ru(p-cymene), and Os(p-cymene) half-sandwich complexes
      containing a chelating 1,2-dicarba-closo-dodecaborane-1,2-dichalcogenolato
      ligand.
AB  - The addition reactions of the 16e half-sandwich complexes [M(eta5
      Cp*)[E2C2(B10H10)]] (Cp*=pentamethylcyclopentadienyl: 1S: E=S, M=Rh; 2S: E=S;
      M=Ir; 2Se: E=Se, M=Ir) and [M(eta6-p-cymene)[S2C2(B10H10)]] (p-cymene=4
      isopropyltoluene; 3S: M=Ru; 4S: M=Os), with acetylene, propyne, and 3
      methoxypropyne lead to the 18e complexes 5-19 with a metal-boron bond in each
      case. The reactions start with an insertion of the alkyne into one of the metal
      chalcogen bonds, followed by B-H activation, transfer of one hydrogen atom from
      the carborane via the metal to the terminal carbon of the alkyne, and concomitant
      ortho-metalation of the carborane. The E-eta2-CC and the C(1)B units are arranged
      either cisoid or transoid at the metal. X-ray structural analyses are reported
      for one of the starting 16e complexes (4S), the cisoid complex 12S (from 2S and
      HC[triple bond]C-CH3), and the transoid complexes 9S and 14S (from 1S and
      HC[triple bond]C-CH2OMe, and from 3S and HC[triple bond]CH, respectively). All
      new complexes 5-19 were characterized by NMR spectroscopy (1H, 11B, 13C, and 77Se
      and 103Rh NMR spectroscopy when appropriate).

PMID- 11843150
TI  - A kinetic study of S-nitrosothiol decomposition.
AB  - Under anaerobic conditions S-nitrosothiols 1a-e undergo thermal decomposition by
      homolytic cleavage of the S-N bond; the reaction leads to nitric oxide and
      sulfanyl radicals formed in a reversible manner. The rate constants, k(t), have
      been determined at different temperatures from kinetic measurements performed in
      refluxing alkane solvents. The tertiary nitrosothiols 1c (k1(69 degrees C) = 13 x
      10(-3) min(-1)) and 1d (k1(69 degrees C) = 91 x 10(-3) min(-1)) decomposed faster
      than the primary nitrosothiols 1a (k1(69 degrees C) = 3.0 x 10(-3) min(-1)) and
      1b (k1(69 degrees C) = 6.5 x 10(-3) min(-1)). The activation energies (E# = 20.5
      22.8 Kcal mol(-1)) have been calculated from the Arrhenius equation. Under
      aerobic conditions the decay of S-nitrosothiols 1a-e takes place by an
      autocatalytic chain-decomposition process catalyzed by N2O3. The latter is formed
      by reaction of dioxygen with endogenous and/or exogenous nitric oxide. The
      autocatalytic decomposition is strongly inhibited by removing the endogenous
      nitric oxide or by the presence of antioxidants, such as p-cresol, beta-styrene,
      and BHT. The rate of the chain reaction is independent of the RSNO concentration
      and decreases with increasing bulkiness of the alkyl group; this shows that
      steric effects are crucial in the propagation step.

PMID- 11843152
TI  - Toward the design and synthesis of lithium-ion intercalation into a coordination
      pi-pi framework host.
AB  - A pi-stacked coordination solid, [[[(VO)2(OH)2(C4O4)(phen)2] x H2O]n] (1: phen =
      phenanthroline), was synthesized by hydrothermal methods and structurally
      characterized by X-ray single-crystal diffraction. The structure of 1 adopts a
      neutral open framework in which channeling apertures and windows are surrounded
      by four oxovanadyl dimers, two squarates, and two pairs of pi-pi interactions of
      phenanthroline groups; the dimensions of the windows are about 5.38 x 7.55 A
      along the c axis. Surprisingly, the porous framework with hydrophilic and
      hydrophobic characteristics was thermally stable up to 250 degrees C, as
      indicated from powder X-ray diffraction patterns and thermogravimetric analysis.
      Further investigation of lithium-ion intercalation into the channel matrix of 1
      was conformed by 7Li NMR spectroscopy and cyclic votammetry measurements. The
      present case represents the first example of a porous coordination solid that
      possesses polar channels capable of mediating lithium-ion insertion.

PMID- 11843153
TI  - Efficient synthesis of tetrasubstituted alkenes by allylsilane-terminated domino
      Heck double cyclisation.
AB  - The domino-Heck double cyclisation of the arylbromides 1, which contain an
      allylsilane and an alkyne moiety and are easily accessible by an addition of the
      corresponding lithiated alkynes 5 to the aldehydes 4, leads to the
      tetrasubstituted alkenes 2 and 3 in good yield. The reaction produces exclusively
      compounds with an E double bond and additionally proceeds with good to excellent
      induced diastereoselectivity in the case of 1e and 1f. Irradiation of 2e leads to
      a steady state equilibrium of the E and Z compounds in a 1:1 ratio.

PMID- 11843154
TI  - End-cap stabilized oligoynes: model compounds for the linear sp carbon allotrope
      carbyne.
AB  - Three series of differently 3,5-disubstituted alpha,omega-diphenylpolyynes Ar
      (C[triple bond]C)n-Ar (n=2, 4, 6, 8, 10) were synthesized under optimized Cadiot
      Chodkiewicz conditions, isolated and completely characterized. These compounds
      can be considered as model substances for the hypothetical one-dimensional carbon
      allotrope carbyne Cx. The longest sp-carbon chain contains 20 atoms and is
      therefore the longest, purely organic polyyne studied with NMR techniques.
      Extinction coefficients over 600,000 M(-1) cm(-1) represent the highest measured
      quantitative values for that compound class so far. Comparisons with previous
      investigations and electrochemical studies allow the assignment of absorption for
      both wavelength regions structuring the UV/Vis spectra. Based on the trends in
      the spectroscopic behaviour of those molecules with increasing chain length,
      electronic as well as the NMR properties of carbyne are predicted, in line with
      our previously reported results. The observed stability properties promise the
      synthesis of even longer polyynes.

PMID- 11843155
TI  - Quantification of aromaticity in oxocarbons: the problem of the fictitious
      "nonaromatic" reference system.
AB  - Despite the extensive research reported in the literature, the concept of
      aromaticity has eluded rigorous quantification. The main reason for this
      undesirable reality is the fact that aromaticity is a differential property.
      While bond orders, atomic charges and electronegativity differences are
      properties of the molecule under analysis, the aromaticity concept often refers
      to the difference between some property of the molecule and that of an artificial
      "nonaromatic" reference system. A rigorous definition of such a reference system
      is non-existing and therefore constituting the main barrier to obtain a
      satisfactory quantification of the aromatic concept. Oxocarbon acids and their
      anions are examples where the criteria of aromaticity that use reference systems
      are unsuccessful, only NICS criterion gives satisfactory results. Wiberg bond
      indexes and 17O NMR chemical shifts are also useful to study such compounds.

PMID- 11843156
TI  - Total synthesis of amiclenomycin, an inhibitor of biotin biosynthesis.
AB  - We describe the first synthesis of amiclenomycin, a natural product that has been
      found to inhibit biotin biosynthesis and, as a consequence, to exhibit antibiotic
      properties. Structure 1, with a trans relationship between the ring substituents.
      had previously been proposed for amiclenomycin on the basis of its 1H NMR
      spectrum. We have prepared the trans and cis isomers 1 and 2 by unequivocal
      routes and we conclude that the natural product is in fact the cis isomer 2. The
      properly substituted cyclohexadienyl rings were constructed first. A
      cycloaddition reaction between 1,2-di(phenylsulfonyl)ethylene and the N
      allyloxycarbonyl diene 13, followed by reductive elimination of the
      phenylsulfinyl groups, gave the cis isomer 15. To obtain the trans isomer, the O
      trimethylsilyl diene was used to give the cis hydroxylated Diels-Alder adduct 33,
      which was transformed into the corresponding trans amino derivative by means of a
      Mitsunobu reaction. The L-alpha-amino acid functionality was introduced by means
      of a Strecker reaction on the aldehydes 16 and 42, followed by enzymatic
      hydrolysis with immobilised pronase.

PMID- 11843157
TI  - Effect of phase behavior and pressure on the constant-volume heat capacity and
      intermolecular interaction of CO2-ethanol and CO2-n-pentane mixtures in the
      critical region.
AB  - Study on the properties of the fluids near the critical point of mixed systems is
      a key for the development of supercritical (SC) technology and for the further
      understanding of the features of supercritical fluids (SCFs). The constant-volume
      molar heat capacity (Cv) of a solution is directly related to the internal
      energy, intermolecular interaction, and the microstructure of the solution. In
      this work, the Cv of CO2-n-pentane and CO2-ethanol systems was determined at
      308.15 K in different phase regions. This work focuses on how the properties of
      the mixtures change with pressure, composition, and the structure of the
      components near the critical point of the mixtures. It was found that at fixed
      composition, a maximum in Cv versus pressure curve exists (Cv(max)) that occurs
      at the pressure at which the isothermal compressibility (K(T)) is the largest. We
      deduced that breaking the "clusters" in the SC mixtures is an endothermic
      process. It is very interesting that Cv increases sharply as the pressure
      approaches the critical point (CP) or bubble point (BP), while Cv is nearly
      independent of pressure and composition at the pressures well above the CP or BP
      pressure, and that the Cv at CP or BP can be several times larger than that at
      the high pressures. It can be deduced that at fixed composition the degree of
      "clustering" changes significantly with pressure near the CP or BP, and is the
      largest at CP and BP.

PMID- 11843159
TI  - Synthesis of alternating polystyrene/poly(ethyleneoxide) branched
      polymacromonomers.
AB  - Newly designed PS/PEO alternating branched polymacromonomers have been obtained
      by polycondensation of alpha-dicarboxy-functionalized polystyrene and alpha
      dihydroxy-functionalized polyethyleneoxide. 4-[3,5
      Bis(methoxycarbonyl)phenoxymethyl]benzyl bromide was used as atom-transfer
      radical polymerization (ATRP) initiator for the synthesis of alpha-dicarboxy
      functionalized polystyrenes. These macromonomers possess low polydispersities and
      molecular weights in the range of 7000 to 100,000, as proved by gel permeation
      chromatography (GPC) and 1H NMR. Alpha-dihydroxy functionalized polyethyleneoxide
      (PEO) was synthesized by treatment of monofunctionalized PEO with 3,5
      bis(benzyloxy)benzoyl chloride. Polycondensation of the alpha-dicarboxy PS with
      the alpha-dihydroxy PEO in solution or in bulk resulted in alternating PS/PEO
      polymacromonomers, which were effectively purified from the unreacted
      macromonomers and characterized by using 1H NMR, GPC, thermal analysis, and
      optical microscopy. Light-scattering measurements in organic solvents like THF or
      dioxane have shown that these polymacromonomers form stable micelles.

PMID- 11843158
TI  - Theoretical prediction of the hydrogen-bond basicity pK(HB).
AB  - Ab initio and DFT calculations on around 65 hydrogen bond or Lewis bases and
      their complexes with hydrogen fluoride have been performed, and a range of
      calculated properties from both free bases and complexes correlated with pK(HB),
      an experimental scale of hydrogen-bond basicity. For the entire range of bases,
      we found that the hydrogen-bond binding Gibbs free energy computed at the B3LYP/6
      31+G(d,p) level of theory linearly correlated with pK(HB). Further improvements
      in the correlation and prediction of pK(HB) were possible with a non-linear fit
      by considering the hydrogen bonding Gibbs free energy of another possible
      stereoisomeric 1:1 complex and/or that of a linear 2:1 complex, which included a
      second hydrogen fluoride.

PMID- 11843160
TI  - Novel bis-betaines and betaines within [1(4)]meta-heterophane frameworks.
AB  - After prior selection of betaine building blocks for the construction of
      quadrupolar heterophane frameworks, a convergent "3+1" synthetic strategy is
      reported for the synthesis of the title macrocycles composed of heterocyclic
      betaine subunit(s). These typify the first example of simple cyclophanes
      constructed out of both highly pi-excessive and highly pi-deficient
      heteroaromatic moieties linked in a 1,3-alternating fashion. The chemical
      reactivity of the quadrupolar heterophanes 1a and 1c toward electrophiles under
      neutral conditions corroborated their bis-betaine structure. The structural
      features of the bis-betaines 1, betaines 2 x PF6 and 5 x X, and the corresponding
      dicationic [1(4)]heterophanes 3 x 2X and 4 x 2Cl were studied by 1H and 13C NMR
      spectroscopy and electrospray ionization mass spectrometry, and confirmed by
      single-crystal X-ray diffraction analysis of macrocycles 1a and 2a x PF6.

PMID- 11843161
TI  - Chelation-assisted Rh(I)-catalyzed ortho-alkylation of aromatic ketimines or
      ketones with olefins.
AB  - Described herein is the Rh(I)-catalyzed ortho-alkylation of aromatic ketimines or
      ketones with olefins. This method showed high reactivity and selectivity to
      monoalkylation for a variety of olefins including 1-alkenes with an allylic
      proton, alpha,omega-dienes, and internal olefins. For a mechanistic study, H/D
      exchange experiments were carried out, which demonstrated that the ortho C-H bond
      could be easily cleaved even at the low temperature of 45 degrees C. The key step
      of this reaction is the formation of a stable five-membered metallacycle by a
      chelation-assisted ortho C-H bond activation. Furthermore, the direct ortho
      alkylation of aromatic ketones with the Rh(I) complex was successfully achieved
      by adding 50 mol % of benzylamine as a chelation-assistant tool.

PMID- 11843162
TI  - Transition metal ion directed supramolecular assembly of one- and two-dimensional
      polyrotaxanes incorporating cucurbituril.
AB  - This paper reports a synthetic strategy to construct one- and two-dimensional (1D
      and 2D) polyrotaxanes, in which a number of rings are threaded onto a
      coordination polymer, by the combination of self-assembly and coordination
      chemistry. Our approach to construct polyrotaxanes with high structural
      regularity involves threading a cucurbituril (CB) "bead" with a short "string" to
      form a stable pseudorotaxane, followed by linking the pseudorotaxanes with metal
      ions as "linkers" to organize into a 1D or 2D polyrotaxane. A 4- or 3
      pyridylmethyl group is attached to each end of 1,4-diaminobutane or 1,5
      diaminopentane to produce the short "strings", which then react with the
      cucurbituril "bead" to form stable pseudorotaxanes. The reaction of the
      pseudorotaxanes with various transition metal ions including CuII, CoII, NiII,
      AgI, and CdII produces 1D or 2D polyrotaxanes, in which many molecular "beads"
      are threaded onto 1D or 2D coordination polymers as confirmed by X-ray
      crystallography. The overall structure of a polyrotaxane is the result of
      interplay among various factors that include the coordination preferences of the
      metal ion, spatial disposition of the donor atoms with respect to the CB beads in
      the pseudorotaxane, and the size and coordination ability of the counteranion.

PMID- 11843163
TI  - Unsaturated dodecahedranes--in quest of the C20H14 1,4,16-triene and C20H12
      1,4,10(14),16-tetraene, and their cations and anions.
AB  - The highly pyramidal, highly strained 1,4,16-dodecahedratriene (4) and C20H12
      1,4,10(14),16-dodecahedratetraene (5) are cage olefins with an intriguing "inner
      life". For 5 DFT calculations give information about the energetic and
      geometrical consequences of one-/two-electron oxidation and reduction. Attempts
      to prepare 4 and 5 through thermal retro[2+2]/[4+2]cycloaddition strategies
      proved unsuccessful. Still, the C20H14/C20H12 cage cations and anions are
      liberated upon electron impact or gas-discharge ionization of their thermally
      extremely stable tris-/tetrakisanthraceno-anellated derivatives. Mass-selection
      (photoelectron (PE) characterization) of the anions failed, however, due to the
      very small anion intensity, the preferential formation of hydrogen-poor ions, and
      minor cage disruption.

PMID- 11843164
TI  - Analytical determination of the [Ln-aminoxyl radical] exchange interaction taking
      into account both the ligand-field effect and the spin-orbit coupling of the
      lanthanide ion (Ln = DyIII and HoIII).
AB  - Numerous compounds in which a paramagnetic LnIII ion is in an exchange
      interaction with a second spin carrier, such as a transition metal ion or an
      organic radical, have been described. However, except for GdIII, very little has
      been reported about the magnitude of the interactions. Indeed, for these ions
      both the ligand-field effects and the exchange interactions between the magnetic
      centers become relevant in the same temperature range; this makes the analysis of
      the magnetic behavior of such compounds more difficult. In this study,
      quantitative analyses of the thermal variations of the static isothermal initial
      magnetic susceptibility measured on powdered samples of the [Ln(NO3)3-[organic
      radical]2] (Ln = DyIII and HoIII) compounds were performed. The ligand-field
      effects on the Ln ions were taken into account, and the exchange interactions
      within a molecule were treated exactly within an appropriate Racah formalism.
      Values of the intramolecular [Ln-aminoxyl radical] exchange parameter have thus
      been rigorously deduced for both the Dy Kramers and Ho non-Kramers ion-based
      compounds. Ferromagnetic [Ln-radical] interactions are found for both the Dy and
      Ho derivatives with J = 8 cm(-1) and J = 4.5 cm(-1), respectively.

PMID- 11843165
TI  - The deprotonation of benzyl alcohol radical cations: a mechanistic dichotomy in
      the gas phase as in solution.
AB  - The gas-phase acidity of ionized benzyl alcohol and of some of its derivatives
      with selected reference bases has been studied by Fourier Transform Ion Cyclotron
      Resonance (FT-ICR) mass spectrometry. The aim was to relate the gas-phase
      reactivity to the behavior in aqueous solution of the radical cations of benzyl
      alcohols bearing methoxy substituent(s) on the phenyl ring which are known to
      undergo deprotonation at both the CH2 and OH groups. The dual reactivity behavior
      is confirmed in the gas phase, in which the prototypical ion, C6H5CH2OH*+, is
      deprotonated at both the CH2 and OH groups, whereas the ring hydrogens are not
      involved. An increasing extent of O-deprotonation is shown as the strength of the
      base increases. Appropriate methyl substitution, as in the radical cations of
      C6H5C(Me)2OH and C6H5CH2OMe, allows only O- or C-acidity. The two processes are
      characterized by comparable thermodynamic features with a Gas-phase Basicity (GB)
      value of 852 kJ mol(-1) for the cumyloxyl radical and 850 kJ mol(-1) for the
      alpha-methoxybenzyl radical. The possible origin of the observed mechanistic
      dichotomy is discussed.

PMID- 11843166
TI  - Autoimmune uveitis in children: clinical correlation between antinuclear antibody
      positivity and ocular recurrences.
AB  - OBJECTIVE: The aim of this study was to identify the correlation between
      antinuclear antibody (ANA) titre and the onset and clinical course of uveitis in
      children with juvenile idiopathic arthritis (JIA) or without any other systemic
      autoimmune disease, i.e., idiopathic uveitis (IU). METHODS: Twenty-two patients
      affected by uveitis were examined. Ten had JIA-associated uveitis, 12 had IU.
      Follow-up ranged from 7 to 101 months. The ANA were titrated three times per year
      and additionally in case of ocular recurrences. All patients were treated with
      immunosuppressive drug combination therapy (IDCT). RESULTS: JIA-associated
      uveitis: ocular recurrences were noted in three ANA-positive patients and in one
      ANA-negative patient. IU uveitis: ocular recurrences were noted in one ANA
      positive and in one ANA-negative patient. No significant rise in ANA titre was
      noted in either group during uveitis recurrence. CONCLUSIONS: (1) ANA had no
      value in predicting the recurrence of uveitis. (2) IDCT does not influence ANA
      production.

PMID- 11843167
TI  - Exercise-induced apoptosis of rat skeletal muscle and the effect of meloxicam.
AB  - The aim of this study was to evaluate the effect of exercise on apoptosis in rat
      gastrocnemius and soleus muscle tissue and to determine the effect of meloxicam,
      a novel non-steroidal anti-inflammatory drug (NSAID), on the ratio of exercise
      induced apoptosis. Forty male Wistar rats were used in the experiments.
      Spontaneous wheel-running was used as an exercise protocol. Rats were divided
      randomly into four groups. Group A (n = 10) was the control group, in which rats
      did not perform any exercise. In group B (n = 10), gastrocnemius and soleus
      muscles were biopsied immediately after exercise. The rats in group C (n = 10)
      were placed back in their cages after exercise and allowed to rest for 48 h,
      after which the gastrocnemius and soleus muscles were biopsied. In group D (n =
      10), rats were given 11 mg meloxicam (Mobic, Boehringer Ingelheim) per kilogram
      body weight per day p.o. for 2 days, after which gastrocnemius and soleus muscles
      were biopsied 48 h after exercise. The terminal deoxynucleotidyl transferase
      mediated deoxyuridine triphosphate (dUTP)-biotin nick end labelling (TUNEL)
      technique was used to detect DNA fragmentation in situ. TUNEL-positive nuclei
      were identified and counted. The apoptosis ratio in gastrocnemius muscle was
      0.50x10(-3)+/-0.96x10(-3) in group A, 5.42x10(-3)+/-3.58x10(-3) in group B,
      3.55x10(-3)+/-3.23x10(-3) in Group C and 3.52x10(-3)+/-1.00 in Group D; the
      ratios in soleus muscle were 0.98x10(-3)+/-1.83x10(-3), 3.03x10(-3)+/-2.78x10(
      3), 4.48x10(-3)+/-3.32x10(-3) and 2.91x10(-3) 1.98x10(-3), respectively. The
      differences between the apoptosis ratios in group A and B, Group A and C, and
      Group A and D were statistically significant (P < 0.05). There was no
      statistically significant difference between group C and D. In conclusion,
      exercise increased apoptosis in gastrocnemius and soleus muscle tissue, and the
      apoptosis ratios were not affected by meloxicam.

PMID- 11843168
TI  - Unchanged global fibrinolytic capacity despite increased factor VIIa activity in
      Behcet's disease: evidence of a prethrombotic state.
AB  - The aim of this study was to evaluate coagulation and fibrinolytic systems in
      Behcet's disease (BD). Accordingly, various parameters of the coagulation and
      fibrinolytic systems were investigated in 39 patients with BD and 31 age- and sex
      matched healthy volunteers as the control group. Seven of these patients with BD
      had histories of thrombotic complication. Three were found to have decreased
      protein S activity, and one patient had diminished protein C activity. Each of
      those patients had experienced a thromboembolic event. Activated protein C
      resistance was present in two patients, one of whom had had a thromboembolic
      episode. Activated FVII (FVIIa), fibrinogen, and cholesterol levels were
      significantly higher in patients with BD than in the control group. In the
      patient group, plasma FVIIa level was inversely correlated with age. Plasma
      global fibrinolytic capacity (GFC) did not differ between the patients and
      control group. No statistically significant difference was found in the GFC and
      FVIIa levels between patients with and without histories of thrombosis. Although
      the coagulation system was activated in vivo in patients with BD, there was no
      reactive activation in the fibrinolytic system to counteract the activated
      coagulation system. These findings suggest a relative hypofibrinolytic state in
      BD.

PMID- 11843169
TI  - Levels of circulating intercellular adhesion molecule-1 in patients with Behcet's
      disease.
AB  - The purpose of this study was to investigate the possible relationship between
      circulating intercellular adhesion molecule-1 (cICAM-1) plasma levels and
      Behcet's disease. Plasma levels of cICAM-1 were measured in 44 patients with
      Behcet's disease and in 30 healthy controls. cICAM-1 levels were higher in
      patients with Behcet's disease than in the controls (P=0.001). The difference was
      more marked between patients with active Behcet's disease and controls (P <
      0.001). cICAM-1 levels were also higher in patients with active Behcet's disease
      than in those with inactive disease (P<0.001). cICAM-1 seems to be related to
      disease activity in Behcet's disease. It may be useful in assessing disease
      activity in Behcet's disease, as well as in monitoring response to treatment.

PMID- 11843170
TI  - Correlation of serum levels of soluble intercellular adhesion molecule-1 with
      disease activity in systemic lupus erythematosus.
AB  - Intercellular adhesion molecule-1 (ICAM-1) is a membrane-bound molecule primarily
      involved in cell-cell adhesive interactions of the immune system. It is a
      cytokine-induced glycoprotein involved in the recruitment of cells into tissues
      undergoing inflammatory responses. The levels of soluble ICAM-1 were measured in
      sera of patients with systemic lupus erythematosus (SLE) using sandwich enzyme
      linked immunoassay. Serum levels (mean +/- SD) of soluble ICAM-1 (sICAM-1) were
      significantly higher in 24 patients with SLE than in 20 controls (372+/-42 ng/dL
      vs 231+/-29 ng/dL, P < 0.001). A statistically significant positive correlation
      was observed between sICAM-1 levels and SLE disease activity index (SLEDAI) score
      in SLE patients, and no correlation was found between sICAM-1 and CRP, SLEDAI and
      CRP, or SLEDAI and ESR in patient groups (P>0.05). These findings suggest that
      sICAM-1 measurement may serve as an additional serologic marker of disease
      activity in patients with SLE.

PMID- 11843171
TI  - Pulmonary tuberculosis in patients with rheumatoid arthritis (four case reports).
AB  - Pulmonary involvement is one of the most common extra-articular manifestations of
      rheumatoid arthritis (RA). We studied four smear-positivepulmonary tuberculosis
      patients who had had RA for 2.5-12 years. Three of them were using
      corticosteroids at the time of diagnosis. The clinical, radiological and
      bacteriological features of all the patients were examined. We conclude that when
      patients with RA have symptoms related to pulmonary involvement, tuberculosis
      should be considered, particularly in developing countries.

PMID- 11843172
TI  - Disabling pansclerotic morphea of childhood and hypogammaglobulinemia: a curious
      association.
AB  - This communication describes a 1.5-year-old girl who presented with multiple
      episodes of infection since early infancy and stiffening of limbs for 2 months.
      Biopsy of the involved areas showed features consistent with pansclerotic
      morphea. Immunoglobulin estimation revealed hypogammaglobulinemia. This unique
      combination of pansclerotic morphea with hypogammaglobulinemia has not been
      reported before.

PMID- 11843173
TI  - Initial presentation of hemolytic uremic syndrome in a boy with systemic lupus
      erythematosus.
AB  - Associating systemic lupus erythematosus (SLE) with an initial presentation of
      hemolytic uremic syndrome (HUS) is rare. We report on a 13-year-old boy admitted
      to our hospital with an initial complaint of bilateral knee pain and multiple
      petechiae on both lower extremities. Diagnosis of atypical HUS was established
      according to the clinical triad of HUS without a veriotoxin-producing organism in
      his stool and the pathological finding compatible to thrombotic microangiopathy.
      In addition, his symptoms fulfilled the 1982 revised criteria for the
      classification of SLE. After methylprednisolone and cyclophosphamide pulse
      therapies, his laboratory findings and general condition improved. No
      plasmapheresis or any plasma infusion was required.

PMID- 11843174
TI  - Complex regional pain syndrome post mastectomy.
AB  - Complex regional pain syndrome includes the previously termed condition reflex
      sympathetic dystrophy. It is a chronic pain disorder diagnosed on the basis of
      symptoms and skin changes and is known to have a psychological element. It is a
      rare complication after surgery, especially mastectomy. We present two females
      who developed this syndrome after undergoing mastectomy for chronic mastalgia.
      These cases demonstrate that amputation of an organ for chronic pain can result
      in reflex sympathetic dystrophy developing in a nearby limb.

PMID- 11843175
TI  - A patient who developed dermatomyositis after suffering for 7 years from
      rheumatoid arthritis.

PMID- 11843176
TI  - New control of mitochondrial membrane potential and ROS formation--a hypothesis.
AB  - A new control of mitochondrial membrane potential delta(psi)m and formation of
      reactive oxygen species (ROS) is presented, based on allosteric ATP-inhibition of
      cytochrome c oxidase at high intramitochondrial ATP/ADP ratios. Since the rate of
      ATP synthesis by the ATP synthase is already maximal at low membrane potentials
      (100-120 mV), the ATP/ADP ratio will also be maximal at this delta(psi)m (at
      constant rate of ATP consumption). Therefore the control of respiration by the
      ATP/ADP-ratio keeps delta(psi)m low. In contrast, the known 'respiratory control'
      leads to an inhibition of respiration only at high delta(psi)m values (150-200
      mV) which cause ROS formation. ATP-inhibition of cytochrome c oxidase is switched
      on and off by reversible phosphorylation (via cAMP and calcium, respectively). We
      propose that 'stress hormones' which increase intracellular [Ca2+] also increase
      delta(psi)m and ROS formation, which promote degenerative diseases and accelerate
      aging.

PMID- 11843177
TI  - Brix from xenopus laevis and brx1p from yeast define a new family of proteins
      involved in the biogenesis of large ribosomal subunits.
AB  - A clone was isolated from a cDNA library from early embryos of Xenopus laevis
      that codes for a highly charged protein containing 339 amino acids. Two putative
      nuclear localization signals could be identified in its sequence, but no other
      known motifs or domains. Closely related ORFs are present in the genomes of man,
      C. elegans, yeast and Arabidopsis. A fusion protein with GFP expressed in HeLa
      cells or Xenopus oocytes was found to be localized in the nucleolus and coiled
      (Cajal) bodies. Moreover, immunoprecipitation experiments demonstrated that the
      new Xenopus protein interacts with 5S, 5.8S and 28S RNAs of large ribosomal
      subunits. The name Brix (biogenesis of ribosomes in Xenopus) is proposed for this
      protein and the corresponding gene. In Saccharomyces cerevisiae, the essential
      gene YOL077c, now named BRX1, codes for the Brix homolog, which is also localized
      in the nucleolus. Depletion of Brx1 p in a conditional yeast mutant leads to
      defects in rRNA processing, and a block in the assembly of large ribosomal
      subunits.

PMID- 11843178
TI  - Mig-6 is a negative regulator of the epidermal growth factor receptor signal.
AB  - In contrast to signal generation and transmission, the mechanisms and molecules
      that negatively regulate receptor tyrosine kinase (RTK) signaling are poorly
      understood. Here we characterize Mig-6 as a novel negative feedback regulator of
      the epidermal growth factor receptor (EGFR) and potential tumor suppressor. Mig-6
      was identified in a yeast two-hybrid screen with the kinase active domain of the
      EGFR as bait. Upon EGF stimulation Mig-6 binds to the EGFR involving a highly
      acidic region between amino acids 985-995. This interaction is kinase activity
      dependent, but independent of tyrosine 992. Mig-6 overexpression results in
      reduced activation of the mitogenactivated protein kinase ERK2 in response to
      EGF, but not FGF or PDGF, stimulation and in enhanced receptor internalization
      without affecting the rate of degradation. The induction of Mig-6 mRNA expression
      in response to EGF, but not FGF, indicates the existence of a negative regulatory
      feedback loop. Consistent with these findings, a possible role as tumor
      suppressor is indicated by Mig-6-mediated inhibition of EGFR overexpression
      induced transformation of Rati cells.

PMID- 11843180
TI  - Ligand-mediated protection against phage lysis as a positive selection strategy
      for the enrichment of epitopes displayed on the surface of E. coli cells.
AB  - We present a novel strategy, termed CISTEM, which allows direct in vivo screening
      of polypeptides displayed on the surface of E. coli cells by a combination of
      ligand-mediated protection and phage-mediated selection. The effectiveness of
      this new approach was demonstrated by displaying the T7.tag on the surface of E.
      coli as a fusion with the outer membrane protein A, the receptor for
      bacteriophage K3. A monoclonal T7.tag antibody was used as protective ligand for
      T7.tag-displaying cells and phage K3 for the elimination of unprotected cells.
      When populations of bacteria, containing between 6 to 10,000 cells displaying the
      T7.tag and approximately 10(8) cells displaying an unrelated OmpA fusion protein,
      were infected with phage K3, specific and antibody-dependent survival of T7.tag
      displaying cells was observed, yielding an enrichment factor of up to 10(7)-fold.
      The CISTEM technology was used to select sequences from a T7.tag-based,
      randomised library and the results were compared to those obtained from selection
      by MACS with the same library. Together, these results reveal a novel in vivo
      screening strategy in which an E. coli phage receptor is used as display plafform
      and selection is performed in suspension upon addition of a protective ligand and
      a bacteriophage. Extentions and modifications of the basic strategy should lead
      to novel applications for the identification of protein-ligand interactions.

PMID- 11843179
TI  - Beta-carotene inhibits growth of human colon carcinoma cells in vitro by
      induction of apoptosis.
AB  - Epidemiological studies suggest that beta-carotene is able to modulate the risk
      of cancer. A number of in vitro studies reported that beta-carotene inhibits the
      growth of cancer cells; however, so far little is known about the molecular
      mechanisms of the antiproliferative effect of beta-carotene. Here we have
      investigated the effects of two beta-carotene preparations, (i) beta-carotene
      dissolved in tetrahydrofuran (final concentration in cell culture medium: 0.5%)
      and (ii) beta-carotene incorporated in a water dispersible bead form, on cultured
      human colon carcinoma cells HT29. The treatment of cells with beta-carotene up to
      30 microM for 72 h led to a significant increase in the cellular beta-carotene
      concentration and formation of retinol. Beta-Carotene showed only low
      cytotoxicity for confluent cells tested up to 30 microM, but at dietary relevant
      concentrations for the intestinal tract (10, 30 microM) beta-carotene was
      strongly cytotoxic for growing cells and induced apoptosis in HT29 cells as
      assessed by the Annexin-V assay (the maximal effect was observed 15 h after
      treatment with beta-carotene). Exposure of cells to retinol at concentrations
      yielding cellular retinol levels similar to those observed by beta-carotene
      treatment had no antiproliferative or cytotoxic effect. Furthermore, beta
      carotene did not affect the activation of the extracellular signal-regulated
      kinases (ERK1 and ERK2) that are essential for cellular growth. In summary, beta
      carotene can inhibit growth of human colon carcinoma cells in vitro by induction
      of apoptosis in proliferating cells.

PMID- 11843181
TI  - Structural and redox properties of the leaderless DsbE (CcmG) protein: both
      active-site cysteines of the reduced form are involved in its function in the
      Escherichia coli periplasm.
AB  - The thiol/disulfide oxidoreductases play important roles in ensuring the correct
      formation of disulfide bonds, of which the DsbE protein, also called CcmG, is the
      one implicated in electron transfer for cytochrome c maturation in the periplasm
      of Escherichia coli. The soluble, N-terminally truncated DsbE was overexpressed
      and purified to homogeneity. Here we report the structural and redox properties
      of the leaderless form (DsbEL-). During the redox reaction, the protein undergoes
      a structural transformation resulting in a more stable reduced form, but this
      form shows very low reactivity in thiol/ disulfide exchange of cysteine residues
      and low activity in accelerating the reduction of insulin. The standard redox
      potential (E'0) for the active thiol/ disulfide was determined to be -0.186 V;
      only one of the two cysteines (Cys80) was suggested to be the active residue in
      the redox reaction. From the aspect of biochemical properties, DsbE can be
      regarded as a weak reductant in the Escherichia coli periplasm. This implies that
      the function of DsbE in cytochrome c maturation can be ascribed to its active
      site cysteines and the structure of the reduced form.

PMID- 11843182
TI  - Polyphenols of cocoa: inhibition of mammalian 15-lipoxygenase.
AB  - Some cocoas and chocolates are rich in (-)-epicatechin and its related oligomers,
      the procyanidins. Fractions of these compounds, isolated from the seeds of
      Theobroma cacao, caused dose-dependent inhibition of isolated rabbit 15
      lipoxygenase-1 with the larger oligomers being more active; the decamer fraction
      revealed an IC50 of 0.8 microM. Among the monomeric flavanols, epigallocatechin
      gallate (IC50 = 4 microM) and epicatechin gallate (5 microM) were more potent
      than (-)-epicatechin (IC50 = 60 microM). (-)-Epicatechin and procyanidin nonamer
      also inhibited the formation of 15-hydroxy-eicosatetraenoic acid from arachidonic
      acid in rabbit smooth muscle cells transfected with human 15-lipoxygenase-1. In
      contrast, inhibition of the lipoxygenase pathway in J774A.1 cells transfected
      with porcine leukocyte-type 12-lipoxygenase (another representative of the 12/15
      lipoxygenase family) was only observed upon sonication of the cells, suggesting a
      membrane barrier for flavanols in these cells. Moreover, epicatechin (IC50
      approx. 15 microM) and the procyanidin decamer inhibited recombinant human
      platelet 12-lipoxygenase. These observations suggest general lipoxygenase
      inhibitory potency of flavanols and procyanidins that may contribute to their
      putative beneficial effects on the cardiovascular system in man. Thus, they may
      provide a plausible explanation for recent literature reports indicating that
      procyanidins decrease the leukotriene/prostacyclin ratio in humans and human
      aortic endothelial cells.

PMID- 11843183
TI  - Total antioxidant capacity and nuclear DNA damage in keratinocytes after exposure
      to H2O2.
AB  - Studies of oxidative stress have classically been performed by analyzing
      specific, single antioxidants. In this study, susceptibility to oxidative stress
      in the human keratinocyte cell line NCTC2544 exposed to hydrogen peroxide (H2O2)
      was measured by the TOSC (total oxyradical scavenging capacity) assay, which
      discriminates between the antioxidant capacity toward peroxyl radicals and
      hydroxyl radical. The generation of H2O2-induced DNA damage, total antioxidant
      capacity and levels of antioxidant enzymes (catalase, superoxide dismutase,
      glutathione reductase, glutathione S-transferase, glutathione peroxidase) were
      studied. Exposure to H2O2-induced DNA damage that was gradually restored while a
      significant reduction in cellular TOSC values was obtained independently of
      stressor concentrations and the degree of DNA repair. Whereas TOSC values and
      cell resistance to H2O2 showed a good relationship, the extent of DNA damage is
      independent from cellular total antioxidant capacity. Indeed, maximum DNA damage
      and cell mortality were observed in the first 4 h, whereas TOSC remained
      persistently low until 48 h. Catalase levels were significantly lower in exposed
      cells after 24 and 48 h. Keratinocytes exposed after 48 h to a second H2O2
      treatment exhibited massive cell death. A possible linkage was observed between
      TOSC values and NCTC2544 resistance to H2O2 challenge. The TOSC assay appears to
      be a useful tool for evaluating cellular resistance to oxidative stress.

PMID- 11843184
TI  - Recombinant cryptic human fibronectinase cleaves actin and myosin: substrate
      specificity and possible role in muscular dystrophy.
AB  - The N-terminal heparin/fibrin binding domain of human plasma fibronectin (pFN)
      contains a cryptic proteinase. The enzyme could be generated and activated in the
      presence of Ca2+ from the purified 70 kDa pFN fragment produced by cathepsin D
      digestion of pFN. In this work we cloned and expressed the serine proteinase,
      designated fibronectinase (Fnase), in E. coli. The recombinant pFN protein
      fragment was isolated from inclusion bodies, subjected to folding and
      autocatalytic degradation in the presence of Ca2+, and yielded an active enzyme
      capable of digesting fibronectin. Cleavage of pFN and the synthetic peptides Ac-I
      E-G-K-pNA and Bz-I-E-G-R-pNA demonstrated identical specificity of the
      recombinant and the isolated fibronectinase. Further investigations of the
      substrate specificity revealed for the first time the muscle proteins actin and
      myosin as being substrates of fibronectinase. The enzyme can be inhibited by
      alpha1-proteinase inhibitor. In the context of induced cathepsin D release, e. g.
      from granulocytes under inflammatory conditions, these results indicate an
      increase in specific proteolytic potential against muscular proteins in
      dystrophic diseases by the release of cryptic fibronectinase.

PMID- 11843185
TI  - Rat tripeptidyl peptidase I: molecular cloning, functional expression, tissue
      localization and enzymatic characterization.
AB  - We purified tripeptidyl peptidase I (TPP I) to homogeneity from a rat kidney
      lysosomal fraction and determined its physicochemical properties, including its
      molecular weight, substrate specificity and partial amino acid sequence. The
      molecular weight of the enzyme was calculated to be 280,000 and 290,000 by non
      denaturing PAGE and gel filtration, respectively, and to be 43 000 and 46 000 on
      SDS-PAGE in the absence and presence of beta-ME, respectively. These findings
      suggest that the enzyme is composed of six identical subunits. The Km, Vmax, kcat
      and kcat/Km values of TPP I at optimal pH (pH 4.0) were 680 microM, 3.7 micromol
      x mg(-1) x min(-1), 33.1 s(-1) and 4.87 x 10(4) s(-1) x M(-1) for Ala-Ala-Phe
      MCA, respectively. TPP I was significantly inhibited by PCMBS and HgCl2, and
      moderately by DFP. These findings also suggest that TPP I is an exotype serine
      peptidase that is regulated by SH reagent. TPP I released the tripeptide Arg-Val
      Tyr from angiotensin III more rapidly than from Ala-Ala-Phe-MCA, and also
      released Gly-Asn-Leu from neuromedin B with the same velocity as from Ala-Ala-Phe
      MCA. Angiotensin III and neuromedin B have recently been found to be good natural
      substrates for lysosomal TPP I. Furthermore, we determined the rat liver cDNA
      structure and deduced the amino acid sequence. The cDNA, designated as lambdaRTI
      1, is composed of 2485 bp and encodes 563 amino acids in the coding region. By
      Northern blot analysis, the order for TPP I mRNA expression was kidney > or =
      liver > heart > brain > lung > spleen >> skeletal muscle and testis. In parallel
      experiments, the TPP I antigen was detected in various rat tissues by
      immunohistochemical staining.

PMID- 11843186
TI  - Determination of NADH in frozen rat brain sections by laser-induced fluorescence.
AB  - Methods to assess metabolism are important analytical tools in neuroscience. The
      fluorophore nicotinamide adenine dinucleotide (NADH) is a parameter of cellular
      metabolism. NADH fluorescence was measured using a laser-based fluorescence
      detector with spectral and temporal filters. Distribution and intensity of NADH
      fluorescence were investigated in frozen brain sections. In sections containing
      hippocampus the intensity of NADH fluorescence was correlated to brain
      structures. In order to investigate the consequences of neurotoxic lesions, 5,7
      dihydroxytryptamine was injected into the dorsal raphe nucleus 4 to 240 days
      prior to the measurement. NADH fluorescence decreased in the affected region by
      50%, indicating that no recovery in metabolic activity had occurred.

PMID- 11843188
TI  - On techniques for the measurement of the mass fractal dimension of aggregates.
AB  - A review is presented of a number of techniques available for the
      characterisation of the structure of aggregates formed from suspensions of sub
      micron particles. Amongst the experimental techniques that have been commonly
      used are scattering (light, X-ray or neutron), settling and imaging and these are
      the focus of this work. The theoretical basis for the application of fractal
      geometry to characterisation of flocs and aggregates is followed by a discussion
      of the strengths and limitations of the above techniques. Of the scattering
      techniques available, light scattering provides the greatest potential for use as
      a tool for structure characterisation even though interpretation of the scattered
      intensity pattern is complicated by the strong interaction of light and matter.
      Restructuring further complicates the analysis. Although settling has long been
      used to characterise particle behaviour, the absence of an accurate permeability
      model limits the technique as a means of determining the porosity of fractal
      aggregates. However, it can be argued that the determination of fractal dimension
      is relatively unaffected. The strength of image analysis lies in its ability to
      provide a great deal of information about particle morphology and the weaknesses
      lie in the difficulties with image processing and sample size as this is a
      particle counting technique. There are very few papers which compare the fractal
      dimension measured by more than one technique. Light scattering potentially
      provides a useful tool for checking settling results. However, further work is
      required to develop proper models for aggregate permeability and flow-through
      effects.

PMID- 11843187
TI  - Human micro-calpain: simple isolation from erythrocytes and characterization of
      autolysis fragments.
AB  - Heterodimeric p-calpain, consisting of the large (80 kDa) and the small (30 kDa)
      subunit, was isolated and purified from human erythrocytes by a highly
      reproducible four-step purification procedure. Obtained material is more than 95%
      pure and has a specific activity of 6-7 mU/mg. Presence of contaminating proteins
      could not be detected by HPLC and sequence analysis. During storage at -80
      degrees C the enzyme remains fully activatable by Ca2+, although the small
      subunit is partially processed to a 22 kDa fragment. This novel autolysis product
      of the small subunit starts with the sequence 60RILG and is further processed to
      the known 18 kDa fragment. Active forms and typical transient and stable
      autolysis products of the large subunit were identified by protein sequencing. In
      casein-zymograms only the activatable forms 80 kDa+30 kDa, 80 kDa+22 kDa and 80
      kDa+18 kDa displayed caseinolysis.

PMID- 11843189
TI  - Interfacial activity of metal ion extractant.
AB  - The interfacial activity of metal ion extractants is discussed. The interfacial
      tension isotherms are processed by matching the Szyszkowski equation, and
      estimation of selected parameters to discuss the interfacial activity of
      extractants. Results are presented in comprehensive tables and figures. The
      interfacial activity depends mainly on three different parameters; type of
      extractant, acidity of the aqueous phase and organic diluent. Strongly acidic
      extractants and protonated amine reagents exhibit the highest interfacial
      activity. The solvating reagents and non-protonated amines are on the opposite
      side of the scale, while the chelating reagents are somewhere in the middle. The
      acidity of the aqueous phase affects the interfacial activity of extractants,
      mainly by the ionisation (protonation and dissociation) of extractant molecules.
      Solvating diluents always decrease the interfacial activity of extractants.

PMID- 11843190
TI  - Methods of theoretical study of vibrational phenomena in liquids--comparative
      analysis.
AB  - In this review, existing theoretical models of vibrational phenomena in liquids
      are analyzed and compared. Most attention is paid to sonoluminescence, sonolysis
      and related phenomena. The criteria of selection of the optimal theoretical model
      involve analyzing experimental results, its usefulness for evaluation of
      thermodynamic and other parameters of the liquid under vibration, simplicity of
      the mathematical solution and the time needed for computing. It is concluded
      that, according to these criteria, the optimal (between existing models) is the
      chemical model of vibration in liquid, while the best perspectives are for its
      combinations with other models.

PMID- 11843191
TI  - Dynamic scaling method and interface growth.
AB  - The dynamic scaling approach is an important tool for describing the time
      evolution of rough interfaces. It computes dynamic scaling parameters alpha and
      beta, which characterize surface and time correlations. Applications of dynamic
      scaling to random deposition and ballistic deposition are discussed. A model of
      random adsorption on fractal substrates is presented. Then the influence of
      surface diffusion on adsorption is analyzed. The dependence of alpha and beta on
      the substrate fractal dimension, together with the dependence of the fractal
      dimension of the gas-solid interface on adsorption coverage are computed.

PMID- 11843192
TI  - Wetting film stability and flotation kinetics.
AB  - Single bubble experiments performed with different size fractions of quartz
      particles and different, but known, contact angles revealed two modes of
      flotation dynamics in superclean water. (1.) A monotonic increase of collection
      efficiency Ecoll with increasing particle size was observed at high particle
      hydrophobicity and, correspondingly, a low wetting film stability (WFS). (2.) At
      low particle hydrophobicity and, correspondingly, high WFS, an extreme dependence
      of Ecoll on particle size was observed. The use of superclean water in our
      experiments prevented the retardation of bubble surface movement caused by
      surfactants or other impurities that is usual for other investigations and where
      particle-bubble inertial hydrodynamic interactions are suppressed. In the present
      study the free movement of the bubble surface enhances particle-bubble inertial
      interaction, creating conditions for different flotation modes, dependent on WFS.
      At the instant of inertial impact, a particle deforms the bubble surface, which
      may cause its rebound. Where the stability of the thin water film, formed between
      opposing surfaces of a bubble and a particle, is low, its rupture is accompanied
      with three phase contact line extension and contact angle formation before
      rebound. This prevents rebound, i.e. the first collision is accompanied by
      attachment. A high WFS prevents rupture during an impact. As a result, a contact
      angle does not arise and rebound is not prevented. However, rebound is
      accompanied by a second collision, the kinetic energy of which is smaller and can
      cause attachment at repetitive collision. These qualitative considerations are
      confirmed by the model quantification and comparison with measured Ecoll. For the
      first time the Sutherland equation (SE) for Ecoll is confirmed by experiment for
      smaller particle sizes and, correspondingly, very small Stokes numbers. The
      larger the particle size, the larger is the measured deviation from the SE. The
      SE is generalized, accounting for the centrifugal force, pressing hydrodynamic
      force and drainage in the low WFS case and, correspondingly, attachment occurs at
      first collision or during sliding. The derived generalized Sutherland equation
      (GSE) describes experimental data at low WFS. However, its application without
      account for possible rebound does not explain the measured extreme dependence in
      the case of high WFS. The theory for drainage during particle impact and the
      beginning of rebound enables conditions for either attachment or rebound in terms
      of the normal component of the impact velocity and the critical film thickness to
      be derived. Combining this condition with the GSE allowed the equation for Ecoll
      to be derived, accounting for attachment area shrinkage and attachment during a
      repetitive collision. This equation predicts the extreme dependence. Thus the WFS
      determines the modes of flotation dynamics and, in turn, probably affects the
      mechanisms, which control the flotation domain. At low WFS its upper boundary is
      controlled by the stability of the particle-bubble aggregate. At high WFS the
      upper boundary can be controlled by rebound because the latter reduces the
      attachment efficiency by a factor of 30 or more even with repetitive collision.

PMID- 11843193
TI  - Kinetics of adsorption from micellar solutions.
AB  - Previous studies on surfactant adsorption mostly deal with dilute systems without
      aggregation in the bulk phase. At the same time, micellar solutions can be more
      important from the point of view of applications. If one attempts to estimate the
      equilibrium adsorption, neglecting the influence of micelles can lead to
      reasonable results. The situation differs for non-equilibrium systems when the
      adsorption rate can increase by an order of magnitude at the increase of the
      surfactant concentration beyond the CMC. A critical survey of various models
      describing the influence of micelles on adsorption kinetics at the liquid-gas
      interface is given and the theoretical results are compared with existing
      experimental data. The theories proposed for the case of large deviations from
      the equilibrium are usually based on some unjustifiable assumptions and can
      describe the kinetic dependencies of adsorption in only a limited number of
      situations. Consequently, only rough estimates of the kinetic coefficients of
      micellization can be obtained from experimental data on dynamic surface tension.
      More rigorous equations can be derived if the system only deviates slightly from
      equilibrium. In the latter case, the agreement between theoretical and
      experimental results is essentially better and measurements of the dynamic
      surface elasticity of micellar solutions allow us to study the micellization
      kinetics.

PMID- 11843194
TI  - Interaction potentials, structural ordering and effective charges in dispersions
      of charged colloidal particles.
AB  - As colloidal dispersions of charged particles exhibit a wide variety of
      commercial, technological and scientific applications, a considerable theoretical
      effort has been devoted to finding an effective interaction potential from
      primitive models. The forces derived from this potential should justify the
      spatial ordering experimentally observed under certain conditions. This paper
      reviews the advances in these theoretical studies as well as some experiments
      (based on the mentioned order) that try to corroborate them. Special attention
      has been paid to the Derjaguin-Landau-Verwey-Overbeek (DLVO) potential. Nowadays,
      many of these theoretical investigations suggest that it could be applied if some
      of its parameters are renormalized. Nevertheless, to achieve a renormalization
      procedure in a strict way (from a primitive model) is a difficult task as a
      result of the size and charge asymmetries between small ions and macroions. Thus,
      several procedures for computing renormalized charges in a simple way have been
      developed. However, the notion of effective charge has also been widely used (as
      a adjustable parameter) in order to justify results found for several kinds of
      colloids (like solid particle dispersions or micellar systems) by means of quite
      different experimental techniques. Renormalization (as well as ion condensation)
      approaches, experiments and the controversial relationship between theoretical
      and phenomenological effective charges are also reviewed in this work.

PMID- 11843195
TI  - Calorimetric effects accompanying ion adsorption at the charged metal
      oxide/electrolyte interfaces: effects of the correlations between the binding-to
      surface energies of various surface complexes.
AB  - As has been shown in our earlier publications, a theoretical description of ion
      adsorption at the real, energetically heterogeneous oxide/electrolyte interfaces,
      involves necessary assumption about the correlations between the adsorption
      energies of the various surface complexes formed at this interface. So far, only
      two extreme models have been considered in such theoretical descriptions: one
      model assuming that high correlations exist, and the other assuming that
      practically no correlations exist. The purpose of this paper is to develop yet
      another description based on a model assuming that some partial correlations
      exist between the adsorption energies of the various surface complexes. The other
      purpose of this publication is to test these three models by analysing some
      experimental data reported so far in literature. Such data sets must include
      necessary information about the enthalpic effects accompanying ion adsorption.
      This is because enthalpic effects are known to be more sensitive to the
      mechanistic models underlying a theoretical description of adsorption systems.
      With such requirements in mind, we have selected three adsorption systems:
      Al2O3/NaCl, TiO2/NaCl and silica/NaCl, for our analysis. Our theoretical
      numerical analysis of the behaviour of these adsorption systems suggests that
      either none or partial correlations exist between the adsorption energies of the
      various surface complexes. However, that analysis also shows, that the present
      accuracy of the experimental data does not allow us to draw more elaborate
      conclusions.

PMID- 11843196
TI  - An evaluation of retrofit engineering control interventions to reduce
      perchloroethylene exposures in commercial dry-cleaning shops.
AB  - Real-time monitoring was used to evaluate the ability of engineering control
      devices retrofitted on two existing dry-cleaning machines to reduce worker
      exposures to perchloroethylene. In one dry-cleaning shop, a refrigerated
      condenser was installed on a machine that had a water-cooled condenser to reduce
      the air temperature, improve vapor recovery, and lower exposures. In a second
      shop, a carbon adsorber was retrofitted on a machine to adsorb residual
      perchloroethylene not collected by the existing refrigerated condenser to improve
      vapor recovery and reduce exposures. Both controls were successful at reducing
      the perchloroethylene exposures of the dry-cleaning machine operator. Real-time
      monitoring was performed to evaluate how the engineering controls affected
      exposures during loading and unloading the dry-cleaning machine, a task generally
      considered to account for the highest exposures. The real-time monitoring showed
      that dramatic reductions occurred in exposures during loading and unloading of
      the dry-cleaning machine due to the engineering controls. Peak operator exposures
      during loading and unloading were reduced by 60 percent in the shop that had a
      refrigerated condenser installed on the dry-cleaning machine and 92 percent in
      the shop that had a carbon adsorber installed. Although loading and unloading
      exposures were dramatically reduced, drops in full-shift time-weighted average
      (TWA) exposures were less dramatic. TWA exposures to perchloroethylene, as
      measured by conventional air sampling, showed smaller reductions in operator
      exposures of 28 percent or less. Differences between exposure results from real
      time and conventional air sampling very likely resulted from other uncontrolled
      sources of exposure, differences in shop general ventilation before and after the
      control was installed, relatively small sample sizes, and experimental
      variability inherent in field research. Although there were some difficulties and
      complications with installation and maintenance of the engineering controls, this
      study showed that retrofitting engineering controls may be a feasible option for
      some dry-cleaning shop owners to reduce worker exposures to perchloroethylene. By
      installing retrofit controls, a dry-cleaning facility can reduce exposures, in
      some cases dramatically, and bring operators into compliance with the
      Occupational Safety and Health Administration (OSHA) peak exposure limit of 300
      ppm. Retrofit engineering controls are also likely to enable many dry-cleaning
      workers to lower their overall personal TWA exposures to perchloroethylene.

PMID- 11843197
TI  - Effects of retrofit emission controls and work practices on perchloroethylene
      exposures in small dry-cleaning shops.
AB  - The effectiveness of commercially available interventions for reducing workers'
      perchloroethylene exposures in three small dry-cleaning shops was evaluated.
      Depending upon machine configuration, the intervention consisted of the addition
      of either a refrigerated condenser or a closed-loop carbon adsorber to the
      existing dry-cleaning machine. These relatively inexpensive (less than $5000)
      engineering controls were designed to reduce perchloroethylene emissions when dry
      cleaning machine doors were opened for loading or unloading. Effectiveness of the
      interventions was judged by comparing pre- and postintervention perchloroethylene
      exposures using three types of measurements in each shop: (1) full-shift,
      personal breathing zone, air monitoring, (2) next-morning, end-exhaled worker
      breath concentrations of perchloroethylene, and (3) differences in the end
      exhaled breath perchloroethylene concentrations before and after opening the dry
      cleaning machine door. In general, measurements supported the hypothesis that
      machine operators' exposures to perchloroethylene can be reduced. However, work
      practices, especially maintenance practices, influenced exposures more than was
      originally anticipated. Only owners of dry-cleaning machines in good repair, with
      few leaks, should consider retrofitting them, and only after consultation with
      their machine's manufacturer. If machines are in poor condition, a new machine or
      alternative technology should be considered. Shop owners and employees should
      never circumvent safety features on dry-cleaning machines.

PMID- 11843198
TI  - Occupational exposure to cotton dust in cottonseed oil mills.
AB  - Air samples were collected at breathing height in the hulling-separation
      department of a modern cottonseed oil mill in Uzbekistan. The average elutriated
      mass concentration measured by standard cotton dust samplers was 4.6 mg/m3, much
      lower than the average total dust concentration measured by stationary personal
      samplers, 12.49 mg/m3, and by personal samplers attached to workers, 14.53 mg/m3.
      Differences in readings among the vertical elutriators, stationary personal
      samplers, and roving personal samplers are attributed to the distinct sampling
      nature and dynamics of these samplers. The data suggest that most of the dust
      consisted of particles larger than 15 microm, the particle size cutoff of the
      vertical elutriator. Differences in readings among stationary and roving personal
      samplers are statistically significant, presumably representing biased sampling
      by the roving personal samplers of regions characterized by high dust
      concentration (due to machines malfunctioning), the nonstatic nature of the
      sampling, and the interaction between the sampler and the worker (the personal
      cloud). Cotton dust concentrations in the hulling-separation room were
      nonuniform, peaking in front of and between the huller-separator pairs. The high
      total mass readings show that workers were exposed to very high levels of
      nonthoracic airborne dust, which upon inhalation tends to deposit in the
      extrathoracic airways. The high elutriated mass concentrations suggest that
      workers were exposed to respirable cotton dust at levels higher than 1 mg/m3 mean
      concentration, the current Occupational Safety and Health Administration (OSHA)
      Permissible Exposure Limit (PEL) for cotton dust. Regressions between dust
      concentrations measured by stationary vertical elutriators and by personal
      samplers attached to workers serve for estimating the potential occupational
      exposure to cotton dust of workers in the hulling-separation room.

PMID- 11843199
TI  - Field evaluation of a transportable open-path FTIR spectrometer for real-time air
      monitoring.
AB  - To effectively and accurately evaluate human exposures to chemicals, it is
      important to quantify mixtures of chemicals in air, at low levels, and in real
      time. The purpose of this study was to evaluate, in the field, a prototype of a
      new transportable instrument that can fill an important gap in methods available
      to industrial hygienists. This instrument is a cross between extractive and open
      path Fourier Transform Infrared spectrometers and measures chemicals passively
      and in real time in the vicinity of the breathing zone. The spectrometer has a
      folded optical path that can be enclosed, similar to an extractive system. The
      enclosure can be removed, enabling the optical path to be open to the atmosphere;
      thus, the instrument could be operated as an open-path spectrometer. A field
      study was conducted in three different occupational settings, including a
      prosthodontics dental laboratory, a surgery recovery area, and a cytology
      laboratory. Chemicals that were identified and quantified included methyl
      methacrylate, nitrous oxide, xylene isomers, toluene, and ethanol. Simultaneous
      side-by-side sampling was conducted with the prototype instrument and recognized
      National Institute of Occupational Safety and Health (NIOSH) analytical methods.
      The distinct infrared "fingerprint" of each chemical made identification and
      quantification of multiple chemicals possible with the prototype instrument. This
      attribute allowed the industrial hygienist to quantify short-term exposures and
      ceiling levels, correlate work practices with concentration levels, evaluate the
      effectiveness of engineering controls, and identify the presence of unexpected
      compounds. There was no significant difference between the mean time-weighted
      averages (TWAs) of the prototype instrument and traditional methods (p > 0.03).
      Regression analysis found good correlation between the two methods with no
      significant differences between the slope and unity and between the y-intercept
      and zero (p > 0.03). The technology and design of the prototype instrument
      incorporated a unique combination of features and advantages not found in other
      methods or instruments. The instrument produced results comparable to recognized
      analytical methods under field conditions and shows promise as a powerful tool in
      industrial hygiene air monitoring applications.

PMID- 11843200
TI  - Occupational exposures in seismic retrofitting operations.

PMID- 11843201
TI  - Ignition hazard from drilling into sealed frames of agricultural equipment.

PMID- 11843202
TI  - Industrial hygiene at the World Trade Center disaster.

PMID- 11843203
TI  - Evaluation of concurrent personal measurements of acrylonitrile using different
      sampling techniques.
AB  - In a retrospective assessment of employee exposure to acrylonitrile (AN) for an
      epidemiological study, investigators from the National Cancer Institute (NCI) and
      the National Institute for Occupational Safety and Health (NIOSH) evaluated the
      feasibility of using historic acrylonitrile air samples without modification. The
      evaluation discussed here was to determine whether the air sampling results
      across plants were comparable. During site visits to each plant conducted between
      1984 and 1986, study investigators collected personal air samples for four days
      on approximately ten jobs per day. During these visits, IHs at seven of the eight
      plants also collected personal samples to compare their sample values to the
      study-collected sample values. Each plant's IH collected these concurrent
      measurements for their own use and independent of the IHs at the other plants.
      The plant IHs had no common sampling protocol but, rather, used professional
      judgment in deciding sampling logistics for their concurrent measurement. In
      addition, each plant IH used a different laboratory to analyze samples (the study
      industrial hygienists used one laboratory). Three sampling methods were used by
      plant industrial hygienists to collect concurrent measurements: charcoal tubes,
      passive monitors, and porous polymer tubes. The study investigators only used
      charcoal tubes. Two hundred and sixty four (264) pairs of concurrent measurements
      were collected. To assess the +/- comparability of the data sets, paired
      observation tests were used. The two sets of charcoal tubes were found to compare
      favorably with each other. The study's charcoal tubes were 1.2 times higher than
      results from plant passive monitors. No correlation was found between the study's
      charcoal tube results and plant porous polymer tube results, although the means
      for 34 pairs of samples were equivalent. As a result of this evaluation, the
      investigators decided that no adjustments would be made to the plant
      measurements. This type of evaluation should be considered when using measurement
      data in multisite epidemiological studies.

PMID- 11843205
TI  - Idiopathic photodermatoses: clinical, diagnostic and therapeutic aspects.
AB  - Idiopathic photodermatoses are a group of photosensitivity dermatoses, which are
      not very frequent with the exception of polymorphous light eruption. Therefore,
      their recognition may not be easy for dermatologists who are not familiar with
      photosensitivity diseases. LEARNING OBJECTIVE: The information in this review is
      intended for giving clinical, diagnostic and therapeutic clues for the correct
      management of patients. Clinical features will be described together with
      diagnostic relevant procedures and usual therapeutic measures.

PMID- 11843204
TI  - Differential pressure response of 25-mm-diameter glass fiber filters challenged
      with coal and limestone dust mixtures.
AB  - This article summarizes results of research conducted by the National Institute
      for Occupational Safety and Health (NIOSH) at its Pittsburgh Research Laboratory.
      The objective of this work was to determine the correlation between the mass (M)
      of respirable coal and limestone dusts collected on 25-mm-diameter glass fiber
      filters mounted in cassettes and the increase in differential pressure (deltaP)
      that develops across the filters when drawing at constant air flow. Test aerosols
      were generated inside a laboratory dust chamber using various coal dusts,
      limestone dust, and mixes of the two. Dusts with different particle size
      distributions were deposited on the filters by sampling from the chamber through
      cyclone preclassifiers at different flow rates. Results show that the
      relationship between differential pressure increase (cm water) and dust mass (mg)
      is linear and can be approximated by the equation deltaP = KM. The K values
      (slopes) range from 1.14 to 1.64, depending on the parent coal of the samples.
      The influence of particle size distribution was also found. The overall K value
      for all the data summarized in this article is 1.35, with R2 = 0.84 for the
      summary equation. When calibrated for individual work sites, or other
      circumstances where great variability in dust characteristics is avoided, the
      relationship between collected dust mass and increase in differential pressure
      may provide an exploitable principle for measurement of respirable dust
      concentrations.

PMID- 11843206
TI  - The invisible melanoma.

PMID- 11843207
TI  - Photodynamic therapy in dermatology: state of the art.

PMID- 11843208
TI  - Vitiligo: news in surgical treatment.

PMID- 11843209
TI  - The use of antidepressant drugs in dermatology.
AB  - This paper provides an updated review of the use of antidepressant drugs in
      dermatology. Some of the psychiatric disorders that are usually comorbid with
      dermatological disorders and respond to antidepressants include major depressive
      disorder, obsessive compulsive disorder, body dysmorphic disorder, social phobia
      and post-traumatic stress disorder usually secondary to trauma and abuse during
      early life. Cutaneous symptoms may be the feature of a primary psychiatric
      disorder, e.g. cutaneous body image problems, dermatitis artefacta, neurotic
      excoriations and trichotillomania, or psychiatric syndromes may be comorbid with
      a primary dermatological disorder such as the association of major depressive
      disorder or social phobia with psoriasis and obsessive compulsive disorder with
      acne excoriee. Some of the salient pharmacological properties of the tricyclic
      antidepressants (TCAs) and the selective serotonin reuptake inhibitor (SSRI)
      antidepressants are reviewed. The review indicates that the SSRI antidepressants
      are potentially beneficial in the management of all the major psychiatric
      syndromes that are encountered in dermatological disorders. The generally more
      favourable side-effect profile of the SSRIs, such as lower cardiotoxicity in
      contrast to the TCAs, has made them the first-line agents for the treatment of
      depression. Furthermore, some of the pharmacological properties of the
      antidepressant agents that are not related to their antidepressant activity, such
      as the histamine H1 blocking effect of TCAs, such as doxepin, amitriptyline and
      trimipramine, are of benefit in dermatological conditions such as urticaria and
      pruritus. This paper reviews the general guidelines for use of antidepressants
      and salient drug-drug interactions resulting mainly from the inhibition of the
      cytochrome P450 (CYP) 2D6 and 3A3/4 isoenzymes by some of the SSRI
      antidepressants. Before prescribing an antidepressant agent, the specific
      guidelines, side-effect profile, drug-drug interactions and most current
      indications should always be obtained.

PMID- 11843210
TI  - Cheilitis granulomatosa.
AB  - Cheilitis granulomatosa is a rare inflammatory disorder with unclear aetiology.
      It is a disorder characterized by recurrent or persistent swelling of one or both
      lips that may be part of the Melkersson-Rosenthal syndrome or may be a
      manifestation of Crohn's disease. An overview of the clinical features,
      histopathology, differential diagnosis, management strategies and prognosis of
      cheilitis granulomatosa is presented and discussed with regard to the literature.

PMID- 11843211
TI  - Multicentric reticulohistiocytosis.
AB  - BACKGROUND: Multicentric reticulohistiocytosis (MR) is a rare histiocytic
      systemic disease mainly affecting the skin and synovia. OBJECTIVE: To present the
      main and newest aspects of MR. METHOD: A review of the current medical
      literature, composing a retrospective study of 96 case reports published world
      wide since 1977. RESULTS: Facial and hand skin nodules with symmetric arthritis
      were the most frequent clinical presentation. The pathognomonic sign of'coral
      beads' and vermicular erythematous lesions bordering nostrils, seems to be very
      characteristic of MR. There is a significant association with cancer. Histiocytic
      cells of MR are best characterized on immunohistochemistry by its
      immunoreactivity for vimentin, CD68 and CD45 and non-reactivity for S-100
      protein, CD34 and factor XIIIa. Although the outcome of the disease is usually
      very limiting for the patients, treatment with immunosuppressive drugs may be
      useful. CONCLUSION: MR is a unique histiocytic proliferative disease with a
      peculiar immunophenotypic pattern and distinctive clinical and histopathological
      aspects.

PMID- 11843212
TI  - Acne inversa (alias hidradenitis suppurativa).
AB  - Acne inversa is a recurrent, suppurative disease manifested by abscesses,
      fistulas, and scarring. Once considered to be a disease of the apocrine glands,
      it is actually a defect of follicular epithelium. Thus, the term hidradenitis
      suppurativa is a misnomer and should be abandoned. In cases of familial acne
      inversa, the pattern of transmission and number of affected individuals are
      consistent with autosomal dominant inheritance. Aetiological factors such as
      hyperandrogenism, obesity, smoking and chemical irritants are not consistently
      associated with the affection. Bacterial involvement is not a primary event in
      acne inversa, but is secondary to the disease process. Potential complications
      include dermal contraction, local or systemic infection due to the spread of
      microorganisms, systemic amyloidosis, arthropathy, and squamous cell carcinoma.
      As spontaneous resolution is rare and progressive disability is the rule, early
      definitive surgical intervention is advisable. The surgical procedure of choice
      in most cases is wide local excision and healing by secondary intention.
      Pharmacotherapeutic drugs, including synthetic retinoids and antiandrogens, do
      not prevent progression of the disease.

PMID- 11843213
TI  - An epidemiological study of acne in female adults: results of a survey conducted
      in France.
AB  - BACKGROUND: Acne is usually perceived as a disease of teenagers, and most
      epidemiological studies have focused on adolescents. OBJECTIVE: The primary
      objective was to investigate the prevalence of acne in a representative sample of
      French females. Information about skin type, life-style factors influencing acne
      and quality of life were also recorded. METHODS: A self-administered
      questionnaire was sent to 4,000 adult women aged 25-40 years, after a validation
      test by three dermatologists. A definition of acne severity, according to
      questionnaire answers, was established before the questionnaire was sent out.
      RESULTS: A total of 3394 women completed the questionnaire of which 3,305 were
      useable. The data showed a prevalence of acne in 17% of the population, and
      physiological acne in 24%. Thus, the total acne prevalence was 41%. Forty-nine
      per cent of the acne patients had acne sequelae (scars and/or pigmented macules).
      Forty-one per cent of adult acne patients had not experienced acne during their
      adolescence. A premenstrual flare and stress was recorded as causing acne in 78%
      and 50%, respectively. Twenty-two per cent of acne subjects were currently
      receiving therapy. For most patients, acne did not severely impair their quality
      of life. CONCLUSION: This study shows a prevalence of acne in 41% of women in the
      general population. A high proportion of these acne cases are late onset acne.

PMID- 11843214
TI  - Treatment of Miescher's cheilitis granulomatosa in Melkersson-Rosenthal syndrome.
AB  - Cheilitis granulomatosa is the most frequent dermatological sign in the
      Melkersson-Rosenthal syndrome. We reviewed 27 cases of this syndrome diagnosed
      and treated in the last 20 years. All the patients were surgically treated and
      received intralesional corticosteroids during surgery and tetracycline
      hydrochloride (500 mg, twice daily) after the operation to prevent recurrence.

PMID- 11843215
TI  - Photodynamic therapy with violet light and topical 6-aminolaevulinic acid in the
      treatment of actinic keratosis, Bowen's disease and basal cell carcinoma.
AB  - BACKGROUND: Most clinical studies using photodynamic therapy (PDT) with topical
      application of delta-aminolaevulinic acid (delta-ALA) use red light because it
      allows greater depth of penetration. However, given the porphyrin-like spectrum
      of delta-ALA-induced photosensitivity, violet light provides a maximal overlap
      with the excitation spectrum of protoporphyrin IX, meaning that PDT with violet
      light uses less light energy to induce the phototoxic reaction. AIM: To study the
      efficacy of violet light in combination with topical delta-ALA PDT in the
      treatment of pre-malignant and malignant skin lesions. METHODS: Eight hours after
      20% delta-ALA was applied topically, photoirradiation was performed with an
      incoherent light source (Philips HPM-10, 400 W) emitting predominantly violet
      light (400-450 nm). Lesions received 10-20 J/cm2 during an exposure time of 30
      min. The 38 subjects treated included three with basal cell naevus syndrome with
      multiple (> 30) superficial and nodular basal cell carcinomas (BCCs), one subject
      had multiple lesions of Bowen's disease, involving 50% of the scalp, and the
      remaining 34 subjects presented a total of 35 superficial BCCs, 10 nodular BCCs,
      four large solar keratoses and five solitary lesions of Bowen's disease. RESULTS:
      Complete remission both clinically and histologically was seen after a single
      treatment in 82% of the superficial BCCs (100% after a second treatment), 50% of
      the nodular BCCs, one of the four solar keratosis lesions (partial remission in
      the other three) and 90-100% of the solitary lesions of Bowen's disease.
      CONCLUSIONS: delta-ALA PDT using violet light appears to be a well tolerated and
      effective alternative treatment for premalignant and malignant skin lesions,
      especially when there are multiple lesions or large patches comprising a large
      area of skin.

PMID- 11843216
TI  - Botulinum toxin A for palmar hyperhidrosis.
AB  - OBJECTIVE: We evaluated the efficacy and safety of intracutaneous injections of
      botulinum toxin A on severe palmar hyperhidrosis. METHODS: Ten patients with
      recalcitrant palmar hyperhidrosis were treated with intercutaneous injections of
      botulinum toxin A (Botox; 200 U for each hand). Patients were followed up to 23
      months (mean +/- SD: 12.1 +/- 6.2 months). RESULTS Botulinum toxin significantly
      reduced abnormal sweating within 1 week in 100% of the patients. In six patients
      with a follow-up of 12 months or more the antisudorific effect lasted 12.3 +/-
      5.5 months. The longest response duration was 22 months. Repeated treatment was
      performed in five patients with unchanged clinical efficacy. The only side-effect
      was tolerable pain from the intracutaneous injections in patients where a nerve
      block was not performed. CONCLUSIONS: Botulinum toxin A (200 U Botox per palm)
      was able to induce long-term remission in palmar hyperhidrosis without
      significant acute and long-term side-effects. Strictly intracutaneous injection
      of small volumes is recommended. So far, response to repeated treatments did not
      show evidence of neutralizing antibody induction.

PMID- 11843217
TI  - Nd:YAG 1064 nm laser in the treatment of facial and leg telangiectasias.
AB  - BACKGROUND: Facial and leg telangiectasias are a frequent cosmetic concern for
      both females and males with various skin types and ages. To date the different
      treatments for these problems, in particular leg telangiectasias, have frequently
      failed or led to negative side-effects. OBJECTIVE: This study examines the
      clinical effects and safety of applications with a 1064-nm Nd:YAG laser system
      (SmartEpil II, DEKA M.e.l.a., Florence, Italy) to treat vessels on the face and
      legs. MATERIALS AND METHODS: Twenty-five subjects with facial telangiectasias
      underwent one treatment at 100 J/cm2, 10 ms and 2 Hz repetition rate. Thirty-two
      subjects with leg telangiectasias, measuring 0.1-3 mm in diameter, were treated
      at 125-200 J/cm2, 10-30 ms and 2 Hz repetition rate. Subjects in this group
      underwent one to five treatment sessions at 8 week intervals. RESULTS: All
      subjects showed visible improvement, with 95-100% clearing of the face
      telangiectasias after only one treatment, and 50-100% clearing of the lower
      extremity vessels after three to five treatments. Transitory hypopigmentation was
      seen in two cases subjected to leg vessel treatment. CONCLUSIONS: Treatment of
      facial and leg telangectasias using a true long pulse 1064 nm Nd:YAG laser is an
      effective and safe method. The relative lack of discomfort combined with a high
      degree of individual satisfaction should play a part in the fairly high level of
      acceptance of this new form of therapy for the treatment of leg and face
      telangiectasias.

PMID- 11843218
TI  - Plasma cell mucositis.
AB  - A case of plasma cell mucositis is described for its rarity. A probable
      aetiological correlation with periodontitis is discussed. The patient showed good
      response to intralesional and topical steroids.

PMID- 11843219
TI  - Resolution of recurrent perianal condylomata acuminata by topical cidofovir in
      patients with HIV infection.
AB  - Anogenital condylomata acuminata are the most frequent clinical manifestation of
      genital human papillomavirus (HPV) infection. Association between human
      immunodeficiency virus (HIV) and HPV infections is frequent (range: 26-60% in
      males). Topical cidofovir (a nucleotide analogue antiviral drug active against a
      broad range of DNA viruses) is a potential treatment for anogenital warts in
      immunocompromised patients. We treated three HIV-infected patients with HPV
      perianal condylomas with topical 1% cidofovir in flexible collodion once a day
      for 2 weeks. The treatment resulted in complete clearance of the HPV lesions. The
      patients experienced mild transient erythema without any other side-effects. None
      of the patients relapsed during the 10-14-month follow-up period.

PMID- 11843221
TI  - The Laugier-Hunziker syndrome.
AB  - Laugier and Hunziker described a syndrome consisting of asymptomatic benign areas
      of hyperpigmentation affecting the lips, buccal mucosa and, in 50%, the
      fingernails. We report a 67-year-old woman with the clinical features of Laugier
      Hunziker syndrome in association with vulval pigmentation. Histology,
      immunohistochemistry and electron microscopy from the various areas of
      pigmentation on the body confirmed the benign nature of the pigmentation. We
      review potential causes of oral and genital pigmentation, and suggest an
      expansion of the original syndrome described by Laugier and Hunziker to include
      more widespread areas of benign hyperpigmentation, which may associated.

PMID- 11843220
TI  - Blue naevus with satellitosis mimicking malignant melanoma.
AB  - Blue naevus is an acquired benign melanocytic naevus. It is a firm, sharply
      defined dark blue to grey-black papule or nodule, which is likely to arise from
      the arrested dermal melanocytes in the dermis. In the last few years, blue naevus
      has attracted much attention due to the recognition of new entities and to its
      confusion with malignant melanoma. We report a 69-year-old man who developed a
      blue-black nodular lesion with satellitosis on his scalp. Although clinically it
      was thought to be a malignant melanoma, histopathological investigation and
      conservative methods such as dermatoscopy and power Doppler ultrasonography did
      not confirm this diagnosis. Histopathological examination excluded malignant
      melanoma, as there were no cellular atypia and mitotic activity in either the
      nodular lesion or the satellitosis. Doppler ultrasonography confirmed the benign
      nature of the lesion. Dermatoscopic examination showed homogeneous steel-blue
      pigmentation with individual blue globules, dots and some brown veils, and
      confirmed the histopathological diagnosis. To the best of our knowledge, our case
      is the third reported case of a blue naevus with satellitosis mimicking malignant
      melanoma.

PMID- 11843222
TI  - Treatment of widespread cutaneous larva migrans with thiabendazole.
AB  - Cutaneous larva migrans (CLM) is a characteristic eruption that is caused by
      penetration and migration in the skin of nematode larvae. Both animal and human
      hookworms have been implicated in the pathogenesis of the condition, with
      Ancylostoma braziliensis and A. caninum being the most common among them. CLM is
      quite common in tropical areas, but, due to travelling, several cases have also
      been described in Europe. We present a patient with CLM who presumably contacted
      the disease during a holiday in Singapore. The patient was treated successfully
      with oral thiabendazole.

PMID- 11843223
TI  - Sporotrichosis masquerading as pyoderma gangrenosum: case report and review of 19
      cases of sporotrichosis.
AB  - We present the case of a 59-year-old woman who had large ulcerations on her right
      leg that were diagnosed initially as pyoderma gangrenosum and treated with three
      immunosuppressive agents (cyclosporin, prednisone and azathioprine) for 6 months.
      Results of a biopsy at 6 months showed numerous cigar-shaped bodies consistent
      with Sporothrix schenckii; identification was confirmed by tissue culture. A
      retrospective review was performed for all cases diagnosed as sporotrichosis from
      tissue culture or biopsy specimens at the Mayo Clinic. Nineteen cases were
      identified. The present case was the only one in which fungal organisms were
      visible on histological examination. The present case emphasizes the importance
      of making a definitive histological diagnosis in unusual ulcer cases or in
      suspected cases of pyoderma gangrenosum before the initiation of
      immunosuppressive therapy. The large number of cigar-shaped bodies in the tissue
      is a rare finding in sporothrix infection and has been reported in only two cases
      previously.

PMID- 11843224
TI  - Five cases of livedo-like dermatitis (Nicolau's syndrome) due to bismuth salts
      and various other non-steroidal anti-inflammatory drugs.
AB  - The authors report five cases of Nicolau's syndrome observed over a period of
      about 25 years. The disease had occurred after intramuscular injections of
      different drugs (bismuth, diclofenac and ibuprofen). In all the described cases
      the clinical aspect was characterized by a livedoid pattern followed by a slow
      necrotizing evolution with scar formation; in some cases surgical debridement and
      plastic reconstructive surgery were performed. In the past Nicolau's syndrome was
      described after intramuscular injections of bismuth salts for the treatment of
      syphilis; now, although still rare, it is described after injections of various
      aqueous drug solutions. The pathogenesis of Nicolau's dermatitis appears to be
      more complex than the previous hypothesized embolism caused by oleous drugs.

PMID- 11843225
TI  - Angioimmunoblastic T-cell lymphoma with cutaneous involvement.

PMID- 11843226
TI  - Confluent and reticulated papillomatosis: failure of response to calcipotriol and
      coincidental association with vascular mottling.

PMID- 11843227
TI  - Current perspectives on the treatment of acne vulgaris and implications for
      future directions.

PMID- 11843228
TI  - New photographic techniques for clinical evaluation of acne.
AB  - Clinical evaluation of acne is usually based on direct visual assessment and
      ordinary flash photography, both of which are compromised by viewer subjectivity.
      It is difficult to accurately assess individual acne lesions and to observe early
      response to therapy. Standard flash photography has inherent limitations owing to
      the physics of light; it does not permit consistent visualization of subtle
      cutaneous characteristics like erythema or microcomedones, and it tends to blur
      distinctions between active inflammatory lesions and older hyperpigmented
      macules. Over the last decade there has been increasing interest in newer
      techniques aimed at increasing the accuracy and objectivity of acne evaluation.
      These include parallel-polarized light photography, cross (or perpendicular)
      polarized light photography, videomicroscopy, and fluorescence photography. This
      article will review the advances of the past decade and summarize new techniques
      to evaluate acne lesions. Moreover, findings of a study that evaluated the course
      of individual acne lesions and the effects of adapalene gel 0.1% on inflammatory
      and non-inflammatory acne lesions will be viewed. In this study, the use of
      parallel-polarized and cross-polarized photography, in combination with
      videomicroscopy and sebum production measurement, provided objective, detailed
      information on the evolution of different variable acne lesions and their
      response to adapalene gel 0.1%. Adapalene treatment produced rapid resolution of
      inflammatory and non-inflammatory lesions, and inhibited formation of new
      lesions. Sebum secretion rates also declined during treatment. Use of the new
      assessment techniques proved to be a valuable, non-invasive and reliable method
      of assessing acne vulgaris and its response to treatment.

PMID- 11843229
TI  - Pivotal clinical trials of adapalene in the treatment of acne.
AB  - Adapalene, a naphthoic-acid derivative, possesses some of the biological
      activities of tretinoin but has distinct physicochemical properties and binding
      properties for selective affinity for retinoic acid receptors. As such, adapalene
      is less likely to be associated with certain local tolerability problems (e.g.
      burning, erythema, pruritus). Over the past 5 years, numerous clinical trials
      have been conducted to compare the efficacy and tolerability of adapalene and
      tretinoin in the treatment of acne vulgaris. Three pivotal, large, well
      controlled studies involving almost 900 patients showed that adapalene gel 0.1%
      and adapalene solution 0.1% are at least as effective as tretinoin gel 0.025%,
      with superior local tolerability. Adapalene cream 0.1% has proven to be
      significantly more effective than vehicle, with response rates comparable to
      those observed with the gel and solution. A meta-analysis of trials with the gel
      formulation confirmed these findings, showing equivalent efficacy and improved
      tolerability vs. tretinoin gel 0.025%. Moreover, the onset of clinical effect was
      shown to be significantly more rapid than that of tretinoin gel. Taken together,
      these studies demonstrated that adapalene has overall efficacy similar to that of
      topical tretinoin, but with a superior therapeutic ratio that may result in
      superior outcomes in clinical practice through improved compliance. This may be
      expected because of its lesser potential for skin irritation, especially early in
      treatment, and because of greater convenience in that no waiting period is
      required between face washing and application of the product. Therefore, 5 years
      of clinical experience have established that adapalene in its various
      formulations is a valuable addition to current treatments for acne vulgaris.

PMID- 11843230
TI  - An update of recent clinical trials examining adapalene and acne.
AB  - Topical retinoids are a mainstay in the treatment of acne vulgaris. In the past
      these agents have been associated with irritant effects, however, newer
      generations of topical retinoids have emerged that have been designed to be less
      irritating. This paper focuses on the newer topical retinoid products, and
      specifically looks at adapalene and recent clinical studies that evaluate its
      efficacy and tolerability. Most of these studies evaluate adapalene in comparison
      with the new tretinoin formulations, which, like adapalene, have been designed to
      be less irritating than their predecessors. The various studies comparing the
      efficacy and tolerability of adapalene with the new formulations of tretinoin are
      described. A summary of the findings and their implications follows.

PMID- 11843232
TI  - Adapalene in the treatment of African patients.
AB  - AIM: To assess the efficacy and safety of topical adapalene gel 0.1% as a
      treatment for acne vulgaris in black South African patients. BACKGROUND: African
      and other darker skin types represent a particular clinical challenge for
      dermatologists treating acne. In many cases, this is due to the higher risk of
      postinflammatory hyperpigmentation in patients with dark skin. Acne vulgaris is
      an extremely common dermatological problem among Africans and people of African
      descent worldwide. Few studies of any of the major acne therapies have been
      carried out in exclusively black populations, and relatively little is known
      about the specific responsiveness of black skin to these agents. The ideal acne
      treatment for black people would specifically target the inflammatory process,
      which so often results in hyperpigmentation. Topical retinoids do this to some
      degree, but they can be highly irritating and this in itself can provoke post
      treatment hyperpigmentation. METHODS: An open-label study of adapalene 0.1% gel
      in 65 black South Africans, aged 12-30, for 12 weeks. Patients all had mild to
      moderate facial acne as defined by the Leeds scoring system; they were instructed
      to apply the medication once daily. Lesion counts and severity scores were
      assessed at 4, 8 and 12 weeks. RESULTS: A total of 44 subjects completed the
      trial and all three follow-up visits. Adapalene gel 0.1% showed clear efficacy
      against both inflammatory and non-inflammatory lesions. The drop in mean total
      facial-lesion count ranged from 46 to 72% between the first and last visit, and
      in most cases, there was clear improvement in cosmesis. In two-thirds of cases,
      patients experienced reductions in both number of hyperpigmented macules and
      density of hyperpigmentation. CONCLUSION: Adapalene gel 0.1% is an effective,
      well-tolerated topical therapy for black patients. It is able to reduce both
      inflammatory and non-inflammatory lesions, as well as prevent and alleviate acne
      associated hyperpigmentation.

PMID- 11843231
TI  - A comparison of adapalene gel 0.1% vs. tretinoin gel 0.025% in the treatment of
      acne vulgaris in China.
AB  - AIM: To compare the efficacy, safety and tolerability of adapalene gel 0.1% vs.
      tretinoingel 0.025% in a Chinese patient population. BACKGROUND: Although acne
      vulgaris is a common problem among Asians and Asian-Americans, little has been
      published on the specific manifestations, sequelae, and treatment-responsiveness
      of this disorder in Asian skin types. Since Asian skin types tend to be more
      highly pigmented than those of white people of European descent, many Asians
      share the predisposition toward postinflammatory hyperpigmentation seen in
      Africans, African-Americans and other dark-skinned peoples. It is generally
      assumed that the efficacy and safety of topical retinoids is the same in Asians
      as in white people. Tretinoin has been available in China for decades; adapalene
      became available in 1998. METHODS: A total of 150 patients with grade II-III acne
      vulgaris seen at three dermatology clinics were randomized to 8 weeks of daily
      treatment with either adapalene gel 0.1% or tretinoin gel 0.025%. Counts of total
      lesions, inflammatory lesions and non-inflammatory lesions were made at baseline
      and again at treatment weeks 2, 4, 6 and 8. Global assessment ratings, based on
      percent lesion reduction from baseline were also made. Erythema, burning,
      pruritus, scaling and dryness were rated on a 0-3 severity scale. RESULTS: A
      total of 139 patients completed the efficacy evaluation, and 144 patients
      completed the safety evaluation. Both adapalene and tretinoin produce dramatic
      reductions in total, inflammatory and non-inflammatory lesion counts, in the
      range of 69-74% on average. More than 70% of patients in both groups had complete
      clearance or marked improvement. In general, irritation was mild, but was both
      more common and more severe in the tretinoin group vs. the adapalene group. No
      systemic side effects were seen. CONCLUSIONS: Adapalene offers comparable
      efficacy to tretinoin, but is less irritating. It represents a good alternative
      for the treatment of mild to moderate acne vulgaris in Chinese patients.

PMID- 11843233
TI  - The integral role of topical and oral retinoids in the early treatment of acne.
AB  - This article will review the rationale for early use of topical retinoids alone
      or in combination with topical antimicrobials in light of the pathogenesis of
      microcomedones and later lesions. Knowledge of the pathogenic processes in acne
      vulgaris has risen dramatically over the last three decades. It is now widely
      accepted that acne is the result of four distinct processes: increased
      proliferation, cornification, and shedding of follicular epithelium; increased
      sebum production; colonization of the follicle with Propionibacterium acnes; and
      induction of inflammatory responses by bacterial antigens and cell signals.
      Clinical focus of disease management has shifted toward earlier treatment
      targeting these fundamental processes. Elimination of microcomedones, the
      precursor to all subsequent lesions, would optimize acne therapy by preventing
      the later inflammatory stages of disease. With the exception of oral
      isotretinoin, no single first-line agent addresses all pathogenic mechanisms.
      Topical retinoids have comedolytic and in some cases anti-inflammatory effects,
      but have no direct impact on P. acnes. Thus treatment with a combination of
      topical retinoid and topical antimicrobial is warranted. The former can also
      enhance penetration of the latter by increasing microcomedonal extrusion. In
      selecting a combination, one must consider efficacy, cost, and likelihood of
      compliance. Once thought to be effective primarily for treating comedones,
      topical retinoids have also been demonstrated to be effective in reducing
      inflammatory lesions. The activity of a topical retinoid combined with an
      antimicrobial agent has been shown to clear more lesions and to clear them more
      rapidly than antimicrobial therapy alone. Topical retinoids are also used
      effectively to maintain remissions.

PMID- 11843234
TI  - Adapalene biochemistry and the evolution of a new topical retinoid for treatment
      of acne.
AB  - The emergence of oral and topical retinoids was a major advance in the clinical
      management of acne vulgaris. However, the benefits of these agents were somewhat
      limited by the degree of side effects caused by these drugs. Over the last 15
      years, researchers have sought compounds that can provide the manifold
      therapeutic benefits obtained with tretinoin and isotretinoin while minimizing
      the potential for irritation and other unwanted effects. Adapalene, a naphthoic
      acid derivative, is one result of this search, and it serves as an example of
      rational drug development: the formulation of a novel substance with specific
      pharmacological properties and clinical objectives in mind. These goals included
      enhancing stability, enhancing anti-inflammatory effects, maintaining
      effectiveness and minimizing cutaneous irritation. This paper reviews the history
      of the development of adapalene, its unique physical and biochemical properties,
      and the pharmacological studies that demonstrate a wide range of retinoid
      receptor, genetic and anti-inflammatory effects, all of which contribute to the
      therapeutic efficacy and improved tolerability of adapalene observed in the
      clinical use of this agent for the treatment of acne.

PMID- 11843235
TI  - Current issues in antimicrobial therapy for the treatment of acne.
AB  - This review summarizes current information regarding the use of antimicrobial
      agents for the treatment of patients with inflammatory acne. A number of drugs
      have been used effectively as topical or systemic therapy, often in combination
      with benzoyl peroxide or a retinoid. Propionibacterium acnes exhibits high in
      vitro sensitivity to a wide range of antimicrobials, including ampicillin,
      clindamycin, erythromycin, tetracycline, doxycycline, nadifloxacin, ofloxacin,
      minocycline, cephalexin, and gentamycin. However, not all of these drugs are
      equally effective in penetrating the lipid-filled microcomedo and reducing
      numbers of P. acnes in the skin. Antimicrobial therapy, particularly systemic
      treatment, may be complicated by the potential for drug-drug interactions.
      Historically, the potential for antimicrobials to reduce the effectiveness of
      oral contraceptives has been a concern in the treatment of acne. However, there
      is evidence to suggest that such an interaction does not take place in patients
      being treated with the antimicrobials most often used in dermatological practice.
      Antimicrobial therapy for acne has also been complicated by the emergence of
      antibiotic-resistant strains of P. acnes. Increasing P. acnes resistance can be
      combated by judicious use of retinoids in combination with antibiotics to reduce
      inflammation and infection, and employment of retinoids for maintenance therapy.

PMID- 11843236
TI  - Endocrinological evaluation and hormonal therapy for women with difficult acne.
AB  - Acne vulgaris is the most common skin condition observed in the medical
      community. Convention is to treat this condition with a combination of
      comedolytics, anti-inflammatory and antibacterial topical agents, or if
      indicated, oral antibiotics or retinoids. In addition to these therapies,
      hormonal therapy is potentially an option in women whose acne is not responding
      to conventional treatment or if signs of endocrine abnormalities are present.
      This paper focuses on the use of hormonal therapy in women with severe or
      recalcitrant acne. After a brief description of the pathogenesis of acne
      vulgaris, and the conventional treatment modalities, indications for hormonal
      therapy are discussed. This is followed by an outline of a suggested endocrine
      evaluation, and interpretation of the evaluation test results. Various options
      for hormonal therapy are then described, including a further discussion of oral
      contraceptives (OCs) in the treatment of acne.

PMID- 11843239
TI  - Drug reimbursement by medicare: a response from ASCO, valid elsewhere?

PMID- 11843237
TI  - Exploration of retinoid activity and the role of inflammation in acne: issues
      affecting future directions for acne therapy.
AB  - The review summarizes new results concerned with several important issues in the
      treatment of patients with acne. The first section reviews studies which show
      that 13-cis retinoic acid, a molecule with strong biological activity but low
      binding affinity for retinoid receptors and cellular-binding proteins in
      sebocytes, undergoes rapid intracellular conversion to all-trans retinoic acid.
      This active metabolite exerts its actions on sebocyte gene expression by binding
      to the nuclear retinoic acid receptor rather than the retinoid X receptor.
      Importantly, 13-cis retinoic acid, unlike all-trans retinoic acid, does not
      induce cytochrome P450 1A1, an enzyme responsible for the metabolism of
      xenobiotics. Thus, administration of 13-cis retinoic acid permits high long-term
      intracellular accumulation of its active metabolite. The second section reviews
      studies which suggest that leukotriene B4 may play a key role in acne-related
      inflammation. Results from a preliminary clinical study indicate that therapy
      with a specific lipoxygenase inhibitor is clinically effective in the treatment
      of patients with inflammatory acne and that its clinical efficacy is correlated
      with the drug's ability to reduce total lipid levels, and especially pro
      inflammatory lipids, in sebum. Interestingly, 13-cis retinoic acid has been shown
      to modulate the activities of LTB4 and inflammatory events in the development of
      acne. Therefore, future compounds targeting acne have to inhibit pro-inflammatory
      lipids in sebum, and thus down-regulate acne-related inflammatory signals and
      reduce the LTB4-induced migration of inflammatory cells.

PMID- 11843240
TI  - Managing poor performance non-small-cell lung cancer patients.

PMID- 11843241
TI  - Adjuvant interferon-alpha for melanoma revisited: news from old and new studies.
AB  - Currently the data from 12 randomised phase III trials investigating the role of
      interferon-alpha (IFNalpha) in patients with stage II-III high-risk melanoma are
      available. The most prominent differences between these trials concern the dose
      of IFNalpha, the duration of IFNalpha administration, and the stage of disease.
      Some of these trials have not yet reached maturity, but despite this the positive
      results from some immature trials have attracted considerable attention. When
      only data from mature trials is considered, one may conclude that the use of high
      dose IFNalpha does prolong disease-free survival (DFS) but not overall survival
      (OS). Combined data from low-dose IFNalpha trials does not suggest a benefit in
      either DFS or OS. A trial with intermediate-dose IFNalpha is still immature.
      Therefore currently the routine use of IFNalpha cannot be recommended outside the
      scope of clinical trials.

PMID- 11843242
TI  - Do all patients with advanced non-small-cell lung cancer benefit from cisplatin
      based combination therapy?
AB  - BACKGROUND: Platinum-based chemotherapy has been shown to be effective in
      improving survival and quality of life in advanced non-small-cell lung cancer
      (NSCLC) patients. The objective of this study was to identify patients more
      likely to benefit from chemotherapy in order to avoid the indiscriminate
      treatment of all patients. PATIENTS AND METHODS: A multivariate analysis of
      survival was performed using the database of the European randomized phase III
      trial that compared vinorelbine (navelbine) (NVB), vinorelbine-cisplatin (NVB-P)
      and vindesine-cisplatin (VDS-P) in 612 patients with inoperable NSCLC (stage III
      or IV). Interactions between treatment and the prognostic factors singled out by
      the Cox procedure were specifically tested. RESULTS: The performance status (PS)
      was the only significant interaction among the selected prognostic factors and
      treatment. Subgroup analysis showed that the advantage obtained with NVB-P
      predominantly concerned PS 0-1 patients, whose median survival lasted 43 weeks
      (95% confidence interval (95% CI): 39-50 weeks) with a one-year survival rate of
      38% (95% CI: 31%-46%) versus 36 weeks (95%, CI: 30-40 weeks) and 34% (95% CI: 27%
      42%) for NVB alone, and 33 weeks (95% CI: 30-39 weeks) and 29% (95% CI: 22%-36%)
      for VDS-P. In sharp contrast, survival in PS 2 patients was similar (median 18
      weeks) (NVB-P 95% CI: 11-34 weeks; NVB 95% CI: 11-35 weeks; VDS-P 95% CI: 14-32
      weeks) whatever the treatment. CONCLUSION: PS 2 patients with advanced NSCLC
      might not benefit from cisplatin combination therapy.

PMID- 11843243
TI  - The benefits of chemotherapy in patient subgroups with unresectable non-small
      cell lung cancer.
AB  - BACKGROUND: Cisplatin-based chemotherapy improves survival in advanced non-small
      cell lung cancer. Using data from phase III trials of mitomycin, ifosfamide and
      cisplatin, this paper investigates whether the beneficial effect of chemotherapy
      on survival and quality of life seen overall is limited to certain patient
      subgroups. PATIENTS AND METHODS: The survival benefit of chemotherapy was
      compared with standard treatment using hazard ratios for subgroups specified by
      stage, sex, age, histology and performance status (PS). The effect on quality of
      life was investigated for three subgroups defined by performance status. RESULTS:
      The overall unstratified hazard ratio for all 797 eligible patients shows a 16%
      reduction in the risk of death with chemotherapy (P = 0.02). This benefit was
      seen for both locally advanced and extensive stage disease (significantly in
      extensive disease). Subgroups defined by sex, age and histology consistently
      benefitted from chemotherapy. The hazard ratios for the three levels of
      performance status suggest that PS2 patients gain no survival benefit from
      chemotherapy. In contrast, these patients experienced the greatest improvement in
      quality of life during the first six weeks of chemotherapy. CONCLUSIONS: Subgroup
      analysis suggests that the prolongation of life from cisplatin-based chemotherapy
      is confined to PS0/1 patients. Palliation is greater in PS2 patients.

PMID- 11843244
TI  - Oral vinorelbine: feasibility and safety profile.
AB  - BACKGROUND: Patient preference as well as concerns and difficulties with
      intravenous access and pharmaco-economic issues have driven the development of
      oral vinorelbine. PATIENTS AND METHODS: Four phase II studies were conducted in
      chemotherapy-naive non-small-cell lung cancer (NSCLC) and as first-line
      chemotherapy of advanced breast cancer (ABC). As recommended in the phase I dose
      finding study, the first step used a weekly dose of 80 mg/m2. This regimen was
      associated with an excessive rate of early deaths (10%) due to complicated
      neutropenia and led to discontinuation of the first two studies. In a second
      step, the dose of 60 mg/m2/week was given for the first three courses and
      subsequently increased to 80 mg/m2/week, in the absence of severe neutropenia.
      RESULTS: One hundred and thirty eight patients (76 with NSCLC and 62 with ABC)
      received this regimen, of whom only five were unable to undergo dose escalation.
      The incidence of febrile neutropenia and neutropenic sepsis were low (2.9 and
      3.6%, respectively). Although severe events were uncommon, nausea/vomiting and
      diarrhoea were frequent and primary prophylaxis with antiemetics should be
      recommended. CONCLUSIONS: Overall, the safety profile of oral vinorelbine at 60
      mg/m2/week for the first three courses with escalation to 80 mg/m2 is
      qualitatively comparable to that of i.v. vinorelbine at standard doses. Similarly
      to i.v. chemotherapy, close haematological monitoring is necessary.

PMID- 11843245
TI  - Phase I and pharmacokinetic study of weekly oral therapy with vinorelbine in
      patients with advanced breast cancer (ABC).
AB  - BACKGROUND: A phase I dose-escalation study of a new formulation of oral
      vinorelbine was conducted to determine the maximum tolerated dose (MTD) of a once
      weekly regimen and preliminary pharmacokinetic profile in patients with advanced
      breast cancer (ABC). Twenty-six patients were treated at dose levels ranging from
      60 to 100 mg/m2/week. Pharmacokinetics was assessed during the first
      administration. PATIENTS AND METHODS: All patients had histologically confirmed
      locally advanced or metastatic breast cancer and had received no more than two
      prior chemotherapy regimens for ABC. RESULTS: The MTD was 100 mg/m2/week due to
      the occurrence of dose-limiting neutropenia, nausea/vomiting and constipation in
      five of six patients. Toxicities at 80 mg/m2/week were manageable, neutropenia
      being the main toxicity (grade 3-4 seen in 10 of 13 patients). Nausea, vomiting
      and diarrhoea were common but rarely severe. Vinorelbine was rapidly absorbed
      with maximum blood concentration (Cmax) of 103.8 +/- 41.6 ng x ml(-1) observed
      1.2 +/- 0.8 hours (Tmax) after administration of 80 mg/m2. Pharmacokinetic
      exposure increased linearly with dose. Area under the concentration-time curve
      (AUC) and concentration measured 24 hours after drug intake (C24h) were
      significantly correlated with depletion of neutrophils. Objective tumour
      responses were reported in 6 of the 14 evaluable patients treated at doses > or =
      80 mg/m2/week. CONCLUSION: The safety profile of oral vinorelbine appears
      comparable to that of intravenous dosing. The recommended phase II dose is 80
      mg/m2/week and requires regular monitoring of neutrophil counts.

PMID- 11843246
TI  - Maspin and mammaglobin genes are specific markers for RT-PCR detection of minimal
      residual disease in patients with breast cancer.
AB  - BACKGROUND: This study evaluates the specificity of some reverse-transcriptase
      polymerase chain reaction (RT-PCR) assays for the detection of residual tumor
      cells in breast cancer patients. The following markers have been analysed:
      carcinoembryonic antigen (CEA), cytokeratins (CK19 and CK20), polymorphic
      epithelial mucin (MUC-1), epidermal growth factor receptor (EGFR), maspin, and
      mammaglobin. RT-PCR was employed to detect breast cancer cells in peripheral
      blood (PB), bone marrow (BM), and stem cell leukoaphereses (PBPC). PATIENTS AND
      METHODS: We evaluated the specificity of our RT-PCR assays on a panel of breast
      cancer specimens (n = 30), on PBPC in patients undergoing high-dose chemotherapy
      (n = 38), on BM (n = 7) and PB (n = 5) samples obtained from patients with breast
      cancer. Marrow cells, PB, and PBPC from normal subjects or hematological tumor
      patients were tested as negative controls. RESULTS: Only maspin and mammaglobin
      met the criteria of sensitivity and specificity required for the detection of
      residual disease; they were expressed in 80% and 97% of breast cancer specimens,
      respectively, and not expressed in normal controls. CK19, CK20. EGFR, MUC-1, and
      CEA were sometimes expressed in normal blood cells and/or hematological tumors.
      CONCLUSIONS: Our data support the notion that maspin and mammaglobin are useful
      markers for RT-PCR detection of minimal residual disease (MRD) in breast cancer
      patients, and that perspective clinical studies are needed to determine wether RT
      PCR assays will be useful in assessing prognosis, tailoring therapy, or
      developing new strategies for ex vivo purging.

PMID- 11843247
TI  - BRCA2 mutation analysis of 87 Spanish breast/ovarian cancer families.
AB  - BACKGROUND: It is estimated that about 5% -10% of breast cancer (BC) cases is due
      to inherited predisposition. Early works reported that 45%-50% of site-specific
      BC families had BRCA1 mutations and 25%-35% BRCA2 mutations. However, these
      percentages could have been overestimated and likely vary among the populations
      studied. PATIENTS AND METHODS: We analysed the BRCA2 gene in 87 Spanish
      breast/ovarian cancer families in which the BRCA1 mutation screening was
      negative. RESULTS: We detected 15 (17.2%) disease-causing mutations and 11
      polymorphisms and unclassified variants. Four mutations were recurrent, and five
      were novel. Seven (47%) mutations were found in site-specific female BC families,
      five (33%) in families with OC cases, and three (20%) mutations in families with
      male BC cases. There was incomplete penetrance of the mutations in some families,
      and considerable phenotypic variations with respect to the age of diagnosis and
      cancer types. CONCLUSIONS: The percentage of mutations detected reinforces the
      possibility that some of these families have mutations in genes other than BRCA1
      or BRCA2 that confer lower BC risks.

PMID- 11843248
TI  - Weekly cisplatin and oral etoposide as treatment for relapsed epithelial ovarian
      cancer.
AB  - BACKGROUND: Response rates to chemotherapy in relapsed, platinum resistant
      epithelial ovarian cancer remain poor. We have explored the effectiveness of
      weekly cisplatin combined with prolonged oral etoposide in this patient group.
      PATIENTS AND METHODS: Forty-two women with relapsed, advanced ovarian cancer were
      treated with cisplatin 60 mg/m2 on days 1, 8, 15, 29, 36 and 43 and oral
      etoposide 50 mg given from day 1-14 and day 29-43. In those who were responding
      and tolerating treatment (n = 13) oral etoposide 50 mg was continued for two
      further cycles (days 1-21 repeated every 28 days). The interval since last
      platinum containing chemotherapy was > 6 months in 28 patients and < 6 months in
      16 patients. RESULTS: Thirty-six patients were evaluable for response according
      to CA 125 criteria giving an overall response rate of 44%. The response rate in
      evaluable patients declined with increasing numbers of previous treatments: 57%
      with one prior treatment, 42% with two, 40% with three or more. The response rate
      in patients who had received platinum chemotherapy within six months prior to
      treatment was 46%. The only significant non-haematological toxicity was nausea
      and vomiting in 4 patients who experienced greater than grade 2 toxicity. The
      number of patients experiencing haematological toxicity more than grade 2 was as
      follows: haemoglobin 3, white blood count 12, platelets 6. Sixteen patients had
      dose delays and two had dose reductions. CONCLUSION: We conclude that this short
      but intensive regimen provides worthwhile response rates, even in those patients
      who would ordinarily be considered refractory to platinum, and has an acceptable
      toxicity profile.

PMID- 11843250
TI  - Impact of surgery on survival in palliative patients with metastatic colorectal
      cancer after first line treatment with weekly 24-hour infusion of high-dose 5
      fluorouracil and folinic acid.
AB  - BACKGROUND: In palliative first-line treatment of colorectal cancer, the
      secondary resection of distant metastases after downstaging has constantly gained
      in importance. The objective of this prospective study was to examine the tumor
      response rate, the toxicity, the median survival time and the prognostic impact
      of metastatic resection after downstaging of consecutively enrolled patients with
      primary nonresectable colorectal cancer treated with once weekly 24-hour (24-h)
      infusion of high-dose 5-fluorouracil (5-FU) and folinic acid. PATIENTS AND
      METHODS: Between January 1995 and July 1997, 53 consecutive patients with primary
      nonresectable metastases were recruited for a prospective phase II study. The
      patients received in out-patient care 500 mg/m2 folinic acid in the form of a 1-2
      hour infusion followed by 2600 mg/m2 5-FU administered as a 24-h infusion once
      weekly. One treatment cycle comprised six weekly infusions followed by a two week
      rest. Three cycles were administered, and in the event of complete remission (CR)
      or partial remission (PR) and good tolerability, a fourth cycle was undertaken.
      Thereafter, the possibility of performing a curative metastatic resection was
      investigated. RESULTS: Of the 53 patients treated, 7 showed a CR (13%), 15
      patients a PR (28%), 26 patients stable disease (SD) (49%), and 5 patients
      progressive disease (PD) (10%). As the main symptom of toxicity, diarrhea (CTC
      grade 3 + 4) was observed in 11 patients (21%), followed by leucocytopenia (CTC
      grade 3 + 4) in 2 patients (4%), and the hand-foot syndrome in 1 patient (2%).
      The median survival time was 17 months with a median follow-up of 41 months
      (range: 28-59 months). In 9 patients (17%), a secondary metastatic resection was
      considered; in 6 patients (11%) curative resection was performed, and 4 patients
      (8%) showed no evidence of disease for at least three years. CONCLUSION: In this
      phase II study, we have been able to show prospectively that, after downstaging
      by palliative treatment using a weekly 24-h infusion of high-dose 5-FU and
      folinic acid, secondary curative metastatic resection was technically feasible in
      11% of the patients. For some of these patients, long-term survival is therefore
      possible. Secondary metastatic resection should be carried out in close
      interdisciplinary cooperation, and should be further investigated in prospective
      phase III studies.

PMID- 11843249
TI  - Randomised trial of SIR-Spheres plus chemotherapy vs. chemotherapy alone for
      treating patients with liver metastases from primary large bowel cancer.
AB  - PURPOSE: SIR-Spheres are radioactive yttrium90 microspheres (SIR-Spheres, Sirtex
      Medical Limited, Australia) used to selectively target high levels of ionising
      radiation to tumors within the liver. This trial was designed to measure any
      increased patient benefit by adding a single administration of SIR-Spheres to a
      regimen of regional hepatic artery chemotherapy (HAC) administered as a 12 day
      infusion of floxuridine and repeated at monthly intervals, vs. the same
      chemotherapy alone. PATIENTS AND METHODS: A phase III randomised clinical trial
      entering 74 patients was undertaken on patients with bi-lobar non-resectable
      liver metastases from primary adenocarcinoma of the large bowel. Patient benefit
      criteria assessed in the trial were tumor response, time to disease progression
      in the liver, overall survival, quality of life, and treatment related toxicity.
      Tumor response was measured by serial changes in both cross-sectional tumor areas
      and total tumor volumes, provided any response lasted not less than three months
      as well as changes in serum carcino-embryonic antigen (CEA). RESULTS: The partial
      and complete response rate (PR + CR) was significantly greater for patients
      receiving SIR-Spheres when measured by tumor areas (44%) vs. 17.6%, P = 0.01)
      tumor volumes (50% vs. 24%, P = 0.03) and CEA (72% vs. 47%, P = 0.004). The
      median time to disease progression in the liver was significantly longer for
      patients receiving SIR-Spheres in comparison to patients receiving HAC alone when
      measured by either tumor areas (9.7 vs. 15.9 months, P = 0.001), tumor volumes
      (7.6 vs. 12.0 months, P = 0.04) or CEA (5.7 vs. 6.7 months, P = 0.06). The one,
      two, three and five-year survival for patients receiving SIR-Spheres was 72%,
      39%, 17% and 3.5%, compared to 68%, 29%, 6.5% and 0% for HAC alone. Cox
      regression analysis suggests an improvement in survival for patients treated with
      SIR-Spheres who survive more than 15 months (P = 0.06). There was no increase in
      grade 3-4 treatment related toxicity and no loss of quality of life for patients
      receiving SIR-Spheres in comparison to patients receiving HAC alone. CONCLUSION:
      The combination of a single injection of SIR-Spheres plus HAC is substantially
      more effective in increasing tumor responses and progression free survival than
      the same regimen of HAC alone.

PMID- 11843251
TI  - Phase I-II study of irinotecan combined with mitomycin-C in patients with
      advanced gastric cancer.
AB  - BACKGROUND: Irinotecan (CPT-11) shows synergism with mitomycin-C (MMC) in a
      preclinical setting. The goals of this study were to determine the maximum
      tolerated dose (MTD), the dose limiting toxicity, the recommended dose (RD), and
      preliminary anti-tumor activity in a combined CPT-11 and MMC treatment of
      advanced gastric cancer. PATIENTS AND METHODS: The study was designed to evaluate
      escalated doses of CPT-11 and MMC administered every two weeks. Five escalating
      dose levels were studied (CPT-11/ MMC: 100/5; 125/5; 150/5; 150/7; 150/10 mg/m2).
      RESULTS: Thirty-one patients were enrolled. Thirty patients were assessable for
      toxicity and tumor response for 89 treatment cycles. The median age was 60 years
      (32-73 years), and most patients (90%) had a performance status of 0 to 1.
      Fourteen patients were previously treated and 17 were chemotherapynaive. The MTD
      was CPT-11 150 mg/m2 plus MMC 10 mg/m2, in which all three patients experienced
      grade 4 neutropenia. including one episode of prolonged and one of febrile
      neutropenia, and one patient experienced grade 3 diarrhea during the first cycle.
      Fifteen partial responses were observed. CONCLUSIONS: The RD based on this phase
      I-II study was CPT-11 150 mg/m2 plus MMC 5 mg/m2 administered every two weeks.
      This combination demonstrates promising activity against advanced gastric cancer
      and warrants further investigation in another phase II study.

PMID- 11843252
TI  - Capecitabine and oxaliplatin in advanced colorectal cancer: a dose-finding study.
AB  - PURPOSE: Capecitabine and oxaliplatin are both active anticancer agents in the
      treatment of patients with advanced colorectal cancer (ACRC). The aim of this
      dose-finding trial was to determine the maximum-tolerated dose (MTD), the dose
      limiting toxicities (DLTs) and the activity of the combination in patients with
      advanced colorectal cancer. PATIENTS AND METHODS: Twenty-five chemotherapy
      pretreated patients received the combination of capecitabine and oxaliplatin.
      Capecitabine was administered orally twice a day continuously for 14 days in
      doses ranging from 1,650 to 2,500 mg/m2/d, and oxaliplatin was administered as a
      two-hour infusion on day 1 using dose, ranges from 100 to 130 mg/m2 repeated
      every three weeks. RESULTS: Twenty-five patients were assessable for toxicity,
      and DLTs were diarrhea (grade > or = 3: 27%) and stomatitis (grade > or = 3: 9%)
      at dose level VI. Dose level V (capecitabine 2500 mg/m2 and oxaliplatin 120
      mg/m2) was found to be the MTD. Hematological toxicity was minimal, overall
      neurotoxicity (grade 1-4) was 27% with 1% grade 3-4. A global response rate was
      17% (95% confidence interval (95% CI): 2%-32%) and the median overall survival
      was 12 months. CONCLUSION: The recommended dose for further phase II studies is
      capecitabine 2,500 mg/m2/d with intermittent schedule and oxaliplatin 120 mg/m2
      every three weeks. The toxicities were mainly gastrointestinal: diarrhea,
      stomatitis and vomiting. This combination should be studied in phase II trials in
      advanced colorectal.

PMID- 11843253
TI  - Phase I study of pegylated liposomal doxorubicin, paclitaxel, and cisplatin in
      patients with advanced solid tumors.
AB  - BACKGROUND: The combination of doxorubicin, paclitaxel, and cisplatin has
      activity in gynecologic malignancies but requires colony stimulating factor (G
      CSF) support. Moreover, there is concern about cardiotoxicity with
      doxorubicin/paclitaxel combinations. Pegylated liposomal doxorubicin may result
      in less myelosuppression and cardiac toxicity than free doxorubicin. The purpose
      of this study was to determine the maximal tolerated dose of pegylated liposomal
      doxorubicin with fixed doses of paclitaxel and cisplatin without using G-CSF
      support in advanced solid malignancies. PATIENTS AND METHODS: Twenty-three
      patients were enrolled; none of the patients had received prior doxorubicin.
      Patients received paclitaxel (90 mg/m2 for dose level one, escalating to 135
      mg/m2 for all subsequent dose levels), with a fixed dose of cisplatin (60 mg/m2),
      followed by escalating doses of pegylated liposomal doxorubicin every 21 days.
      RESULTS: A total of 73 cycles was administered. Grade 4 neutropenia was seen
      after cycle one in two of eight patients receiving 30 mg/m2 of pegylated
      liposomal doxorubicin and three of seven patients receiving 40 mg/m2 of pegylated
      liposomal doxorubicin when combined with 135 mg/m2 of paclitaxel and 60 mg/m2 of
      cisplatin. Two additional patients at the 40 mg/m2 dose level developed grade 4
      neutropenia following cycles 2 and 5. The mean decline in left ventricular
      ejection fraction (LVEF) after 2 cycles was 5 percentage points (P = 0.012).
      CONCLUSION: The combination of pegylated liposomal doxorubicin, paclitaxel and
      cisplatin is feasible without G-CSF support.

PMID- 11843256
TI  - Hand-foot syndrome associated with short infusions of combination chemotherapy
      with gemcitabine and vinorelbine.
AB  - The hand-foot syndrome (palmar-plantar erythrodysesthesia) is a side-effect which
      is associated with several cytotoxic agents (e.g. 5-fluorouracil, UFT,
      capecitabine, cytarabine, doxorubicin, liposomal-encapsulated doxorubicin). An
      association with a prolonged infusion of high doses of vinorelbine has also been
      described. To date a hand-foot syndrome after gemcitabine or short infusions of
      vinorelbine has not been reported before. The patient described here had a non
      small-cell lung cancer stage IIIB disease and developed a hand-foot syndrome
      after short infusions of standard-dose chemotherapy of a combination with
      gemcitabine and vinorelbine.

PMID- 11843257
TI  - Gastrointestinal metastases in lobular breast cancer.

PMID- 11843254
TI  - Tandem autotransplant as first-line consolidative treatment in poor-risk
      aggressive lymphoma: a pilot study of 36 patients.
AB  - PURPOSE: In the previous LNH87-2 study, consolidative high-dose therapy followed
      by stem cell transplantation (HDT) improved disease-free survival, as well as
      survival for patients (pts) presenting with two or three factors of the age
      adjusted international prognostic index (Aa-IPI) in first complete remission
      (CR). In order to improve further the outcome of such patients, we conducted a
      pilot study of consolidative tandem autotranplant. PATIENTS AND METHODS: Thirty
      six patients (pts) under 60 years of age with two or three factors of the Aa-IPI
      were enrolled. Their main characteristics were: diffuse large B-cell lymphoma
      (83%), Aa-IPI three factors (50%), and marrow involved (36)%. The procedure
      consisted of 1) induction with four cycles of ACVBP (doxorubicin,
      cyclophosphamide, vindesine, bleomycin, prednisone) 2) in responding pts,
      peripheral blood stem cell (PBSC) collection after the fourth cycle of ACVBP (11
      pts) or after an additional mobilization regimen (Cyclophosphamide-VP16) (17 pts)
      3) a first HDT (mitoxantrone, cyclophosphamide, VP16 and carmustine) followed by
      PBSC infusion 4) a second HDT (busulfan, carboplatin and melphalan) followed by
      PBSC infusion. Among the 29 patients responding to induction, 28 received the
      first HDTand 24 the second. RESULTS: The rates of three-year-event free survival
      and survival are 47% (95% confidence interval (95% CI: 31%-63%) and 50% (95% CI:
      37%-69%), respectively. Eighteen patients remained free of evolutive disease and
      18 patients have died, 15 from disease progression and three from treatment
      related toxicity after tandem transplant (two veno-occlusive disease and one
      cerebral toxoplasmosis). CONCLUSION: We conclude that tandem transplant did not
      improve the results of the LNH87-2 study in which patients received a single
      consolidative HDT.

PMID- 11843255
TI  - Carcinomatous meningitis as a clinical manifestation of pancreatic carcinoma.
AB  - Carcinomatous meningitis (CM) is clinically less common than brain metastasis or
      spinal cord compression, having dire consequences for both the quality of life
      and the overall survival of patients with solid tumors. It occurs in about 5% of
      all adult cancer patients, but autopsies may double this number. If leukemia and
      lymphoma are excluded, most cases are due to breast cancer, lung cancer and
      melanoma. In this report, we describe a 49-year-old male patient with metastatic
      pancreatic adenocarcinoma who developed carcinomatous meningitis. To our
      knowledge, this is only the second case of carcinomatous meningitis secondary to
      a pancreatic carcinoma described so far.

PMID- 11843258
TI  - Detection of tyrosinase mRNA in tumor tissue microdissections from classic
      Kaposi's sarcoma.

PMID- 11843260
TI  - Immunization registry use and progress--United States, 2001.
AB  - Immunization registries are confidential, population-based, computerized
      information systems that collect vaccination data about all children within a
      geographic area. Registries are key tools used to increase and sustain high
      vaccination coverage by providing complete and accurate information on which to
      base vaccination decisions. Registries consolidate vaccination records of
      children from multiple healthcare providers, identify children who are due or
      late for vaccinations, generate reminder and recall notices to ensure that
      children are appropriately vaccinated, and identify provider sites and geographic
      areas with low vaccination coverage. One of the national health objectives for
      2010 is to increase to 95% the proportion of children aged <6 years who
      participate in fully operational population-based immunization registries
      (objective 14-26). CDC analyzed data from 50 states and the District of Columbia
      (DC) from the calendar year 2000 Immunization Registry Annual Report (CY 2000
      IRAR) to assess current registry activity. This report summarizes the results of
      those analyses, which indicate that 32 (63%) of the 51 grantees are operating
      population-based immunization registries (Figure 1). These 32 projects represent
      49% of the U.S. population aged <6 years.

PMID- 11843261
TI  - Emergency medical system responses to suicide-related calls--Maine, November 1999
      October 2000.
AB  - Suicidal acts are morbid and potentially lethal events that are risks for
      subsequent completed suicide and possibly other health problems (e.g., substance
      abuse and depression). Suicidal behavior also can have negative consequences on
      family members, friends, and caregivers. In 1996, the cost of health care and
      lost wages for suicide attempts in Maine was approximately $115 million. In 1999,
      a total of 1,079 persons were hospitalized in Maine for self-injurious behavior.
      Although Maine has no injury-related surveillance systems, the Maine Bureau of
      Health (MBOH) assessed the use of Emergency Medical Service (EMS) response data
      to estimate incidence of EMS responses to suicide-related calls in Maine and to
      summarize the distribution of these responses by patient and event
      characteristics. This report describes EMS suicide-related responses during
      November 1999-October 2000 and indicates that EMS data would be a useful
      component of an integrated statewide suicidal behavior surveillance system.

PMID- 11843259
TI  - Recent trends in mortality rates for four major cancers, by sex and
      race/ethnicity--United States, 1990-1998.
AB  - In 1998, 53% of all cancer-related deaths in the United States were associated
      with four sites: lung/bronchus, colon/rectum, prostate, and female breast. Cancer
      related death does not affect racial/ethnic populations similarly. In 1996, the
      National Cancer Institute (NCI) published cancer incidence and death rates during
      1988-1992 in 10 categories of race/ethnicity. To examine trends during 1990-1998
      in annual death rates for the four major cancers by sex and race/ethnicity (i.e.,
      blacks, whites, Hispanics, American Indians/Alaska Natives [AI/ANs], and
      Asians/Pacific Islanders [APIs]), CDC analyzed data from the National Center for
      Health Statistics' National Vital Statistics System. This report summarizes the
      results of that analysis, which indicated that, except for lung cancer in women
      and lung, colorectal, and breast cancer in AI/ANs, trends in death rates from
      these cancers have generally declined. But the rates remained high for blacks,
      have not decreased equally among all populations, and have increased in certain
      instances. Continuing research and prevention efforts are needed to reach high
      risk and underserved populations and to understand the reasons for differences in
      cancer mortality among racial/ethnic populations.

PMID- 11843262
TI  - Lipoic acid confers protection against oxidative injury in non-neuronal and
      neuronal tissue.
AB  - In the past decade or so, a convincing link between oxidative stress and
      degenerative conditions has been made and with the knowledge that oxidatiye
      changes may actually trigger deterioration in cell function, a great deal of
      energy has focussed on identifying agents which may have possible therapeutic
      value in combating oxidative changes. One agent which has received attention,
      because of its powerful antioxidative effects, particularly in neuronal tissue,
      is lipoic acid.

PMID- 11843263
TI  - Taurine as a micronutrient in development and regeneration of the central nervous
      system.
AB  - Taurine is an amino acid known to possess trophic properties in the central
      nervous system. The relevance of its presence in maternal milk is related to its
      role as an essential nutrient. Taurine deficiency around birth produces
      anatomical and functional modifications in the brain and in the retina. In
      addition, taurine favors neuron proliferation and survival, as well as neurite
      extension. The mechanisms by which taurine exerts its trophic role in the
      regenerating retina are related to increases in calcium fluxes, to modifications
      of protein phosphorylation, and to influence of the target organ. Moreover,
      taurine-zinc interaction might be crucial in the development of structures such
      as the hippocampal formation. Thus, taurine can be considered as one of the
      determinant nutritional molecules during development and regeneration of the
      central nervous system.

PMID- 11843264
TI  - A study of the behavioral effects of prenatal ethanol exposure in mice fed a diet
      marginally deficient in essential fatty acids for two generations.
AB  - This study investigated the effects of prenatal ethanol exposure on measures of
      fecundity, growth, behavioral development and learning in mice that had been fed
      a diet, marginal in essential fatty acid (EFA) content for two generations. The
      first generation of mice were fed one of two diets (adequate or marginal EFA)
      from conception. They were mated at 10 weeks, and from days 5 to 17 of gestation
      dams on each diet were fed equivalent daily amounts of a liquid diet containing
      either 22.5% of the calories as ethanol or with maltose-dextrin substituted
      isocalorically for ethanol. An additional control group was fed lab chow ad
      libitum. Offspring were maintained on their respective diets after weaning. The
      marginal-EFA diet led to a large increase in perinatal mortality; it also
      decreased body and brain weight in the surviving pups, and retarded behavioural
      development. Ethanol retarded behavioral development in females, and delayed the
      acquisition of learning the position of an escape platform in a T water-maze in
      the mice fed the adequate-EFA diet. The effects of ethanol did not appear to be
      worse in the mice fed the marginal-EFA diet, but these data must be considered in
      light of the high mortality on this diet, where only the healthiest pups may have
      survived.

PMID- 11843266
TI  - Relationship between plasma cyclo (His-Pro), a neuropeptide common to processed
      protein-rich food, and C-peptide/insulin molar ratio in obese women.
AB  - Cyclo (His-Pro) (CHP) is a gut-brain peptide whose plasma levels in humans are
      increased after glucose ingestion and preferentially altered by oral glucose
      ingestion compared to intravenous administration in rats, suggesting a role in
      the enteroinsular response to nutrient ingestion. We were interested in examining
      levels of CHP in women of differing weights and comparing these levels to various
      parameters of insulin secretion. Plasma from 26 fasting, nondiabetic women
      ranging from 21 to 70 years of age and weighing 43 to 114 kg was assayed for CHP.
      Insulin and C-peptide levels were measured in 17 of the 26. Fasting CHP levels
      were elevated in obese compared to nonobese women (2075+/-144 vs. 905+/-187
      pg/ml; p < 0.001) and were related by regression analysis to weight (r = 0.668, p
      < 0.001) and body mass index (r = 0.636, p = 0.001). The fasting C
      peptide/insulin molar ratio, which may be used as an estimate of hepatic insulin
      clearance (HIC), was inversely related to CHP levels (r = -0.568, p = 0.017). We
      conclude CHP levels are increased in obese women and inversely related to their C
      peptide/insulin molar ratio. The elevation of CHP in those with a decrease in
      this estimate of HIC (obese) is interesting as the greater insulin response seen
      in normal persons after oral glucose compared to intravenous glucose has been
      postulated to be due to a decrease in HIC by some gut factor. The presence of
      such a factor in excess in the obese might explain part of their
      hyperinsulinemia.

PMID- 11843265
TI  - Differential effects of dietary cholesterol on aminopeptidase A, B and M in the
      frontal cortex of male and female mice.
AB  - Although hypercholesterolemia and hypertension have been extensively associated,
      the regulatory mechanism underlying this relationship is poorly understood.
      Systemic and local renin-angiotensin systems are involved in the control of blood
      pressure. Angiotensin II has been considered as the main effector peptide of
      renin-angiotensin system. However, other peptides derived from the metabolism of
      angiotensin II, as angiotensins III and IV have been shown to play significant
      roles. The aim of this study is to analyse the effect of dietary cholesterol on
      the activity of the enzymes involved in the metabolism of angiotensins II and
      III. Soluble and membrane-bound aminopeptidase A (aspartyl- and glutamyl
      aminopeptidases), B (arginyl-aminopeptidase) and M (alanyl-aminopeptidase)
      activities were measured in the frontal cortex of male and female mice fed a
      cholesterol enriched-diet (1% cholesterol; 0.5 cholic acid). Soluble and membrane
      bound aminopeptidases B and M did not change in male or female cholesterol
      groups. Significant increases were observed in membrane-bound aspartyl- and
      glutamyl-aminopeptidase activities in both cholesterol groups. Soluble aspartyl-
      and glutamylaminopeptidases did not change in male cholesterol group, but
      significant decreases were detected in female cholesterol group. Our results may
      indicate that the metabolism of angiotensin II to angiotensin III by
      aminopeptidase A is increased, but angiotensin III metabolism by aminopeptidases
      B and M is not modified after cholesterol intake; so cholesterol may enhance the
      effects of angiotensin III, at least, at the cortical level.

PMID- 11843268
TI  - Benefits and rationale of differential bracket slot sizes: the use of 0.018-inch
      and 0.022-inch slot sizes within a single bracket system.

PMID- 11843267
TI  - Effect of perinatal food deficiencies on the compound action potential evoked in
      sensory nerves of developing rats.
AB  - The aim of this study was to analyze the possible alterations produced by
      inadequate perinatal food intake, in quantity (undernutrition) or quality
      (malnutrition), on the generation and propagation of the compound action
      potential (CAP) evoked in sensory sural nerves, during the postnatal development
      of the rat. Low intensity stimulation (2-3 times the threshold of the most
      excitable nerve fibers; xT) of the sural nerve evoked an early potential (CAP-A
      component) which is due to activation of low-threshold, fast-conducting
      myelinated group A afferent fibers. Meanwhile, at higher stimulus intensity (20
      30T) it produced a second, long-lasting potential (CAP-C component) probably due
      to activation of high-threshold, slow-conducting group Adelta or C afferent
      fibers. Compared to control nerves, the CAP-A component, but not the CAP-C
      component of undernourished and malnourished nerves showed significant changes in
      amplitude, area, electrical threshold and conduction velocity (except absolute
      refractory period) at several postnatal ages. Our results may suggest that a
      relative large number of myelinated group A afferent fibers in the sural nerve of
      undernourished and malnourished animals suffer severe alterations on their
      electrophysiological properties of generation and propagation of the action
      potential during the postnatal development of the rat.

PMID- 11843269
TI  - Does malocclusion affect masticatory performance?
AB  - This purpose of this study was to evaluate the largely untested assumption that
      malocclusion negatively affects masticatory performance. A sample of 185
      untreated subjects (48% male and 52% female) from 7 to 37 years of age,
      representing subjects with normal occlusion (n = 38), Class I (n = 56), Class II
      (n = 45), and Class III (n = 46) malocclusion, were evaluated. Masticatory
      performance was evaluated objectively using artificial (CutterSil, median
      particle size and broadness of the distribution) and real foods (number of chews
      for jerky and almonds), and subjectively using a visual analog scale. The results
      showed no significant differences in age or the body mass index (Wt/Ht2) between
      the occlusion groups. Subjects with normal occlusion had significantly smaller
      particle sizes (P = .001) and broader particle distributions (P < .001) than
      subjects with malocclusion. Compared with the normal occlusion group, the median
      particle sizes for the Class I, II, and III malocclusion groups were
      approximately 9%, 15%, and 34% larger, respectively. There were also significant
      group differences in their subjective ability to chew fresh carrots or celery (P
      = .019) and firm meat (P = .003). Class III subjects reported the greatest
      difficulty, followed by Class II subjects, Class I subjects, and subjects with
      normal occlusion, respectively. We conclude that malocclusion negatively affects
      subjects' ability to process and break down foods.

PMID- 11843270
TI  - Facial asymmetry in subjects with skeletal Class III deformity.
AB  - We investigated the frequency, site, amount, and direction of facial asymmetry in
      human adults with mandibular prognathism and examined if these characteristics
      were associated postnatally with cardinal clinical signs that may indicate a
      predisposition to facial asymmetry. Two hundred twenty young Japanese adults (69
      men and 151 women) who exhibited skeletal Class III malocclusions were selected.
      The sample was divided into a Postnatal Factor Group and a Nonpostnatal Factor
      Group. The former group included those who had: (1) received orthodontic
      treatment using a chin cap; (2) exhibited clinical symptoms of temporomandibular
      joint (TMJ) disorder; (3) reported a history of maxillofacial trauma; or (4)
      radiographic abnormality of the condyles. Subjects with a deviation of more than
      2 mm from the facial midline associated with any of the 4 landmarks (ANS, U1, L1
      and Me) were classified as asymmetric and the asymmetry was measured on a postero
      anterior (P-A) cephalogram. Radiographic facial asymmetry was found frequently
      (70%-85%, for Menton), and most obviously in the lower jaw (P < .05). Lateral
      displacement toward the left side of the face occurred more often than right
      sided deviation (P < .001, for Menton). However, the Postnatal Factor Group
      showed a higher proportion of subjects with lateral deviation toward the right
      side (P = .0031) and a greater amount (P < .0001) of chin deviation. This was due
      to the fact that the subjects having TMJ problems as a postnatal factor showed no
      directional uniqueness in jaw deviation and exhibited a longer distance of
      deviation.

PMID- 11843271
TI  - Effect of head rotation on posteroanterior cephalometric radiographs.
AB  - The purpose of this study was to identify the potential projection errors of
      posteroanterior cephalometric radiographs due to head rotation in the vertical Z
      axis. For this investigation, 20 human dry skull samples with permanent dentition
      were collected from the Department of Anatomy in the College of Medicine, Chosun
      University, Korea. They had no gross asymmetries and were well preserved. Each
      dry skull was rotated from 0 degrees to +/- 10 degrees at 1 degrees intervals. A
      vertical axis, the Z-axis, was used as a rotational axis for the exposure of 420
      posteroanterior cephalometric radiographs. Most of the abscissa values of each
      landmark showed statistically significant differences in the head rotation from
      each rotational angle (P < .05), whereas the ordinate values were almost the same
      in all rotational angles regardless of the head rotation. The abscissa values of
      each landmark anterior to the vertical rotational axis displaced in the same
      direction as the head rotation, whereas those of other landmarks posterior to the
      vertical rotational axis displaced in the opposite direction. The mean
      differences of the abscissa values, per 1 degrees of head rotation, were larger
      as the landmark was located further anteroposteriorly from the vertical
      rotational axis and smaller as the landmark was located nearer the vertical
      rotational axis. In view of the projection error, a posteroanterior cephalometric
      radiograph is a more valuable diagnostic tool when it is exposed with no head
      rotation about the vertical Z-axis.

PMID- 11843272
TI  - Effects of maxillary protraction on craniofacial structures and upper-airway
      dimension.
AB  - This study was conducted to examine the effect of treatment with a maxillary
      protraction appliance on the development of the craniofacial structures and upper
      airway dimensions. A total of 25 patients (mean age: 9.8 years) with Class III
      malocclusions were evaluated by the use of lateral cephalograms. A significant
      increase in maxillary forward growth, inhibition of mandibular forward growth,
      and clockwise rotation of the mandible were observed. The maxillary incisors were
      significantly proclined and the mandibular incisors significantly retroclined. A
      multiple-regression analysis revealed that maxillary growth had a significant
      positive effect on the superior upper-airway dimension. These findings indicate
      that the superior upper-airway dimension can be altered during maxillary
      protraction.

PMID- 11843273
TI  - Nocturnal masseter and suprahyoid muscle activity induced by wearing a bionator.
AB  - The purpose of this study was to examine the effect of a bionator on masseter and
      suprahyoid muscle activities during sleep. Ten healthy Japanese males (mean age:
      26.3 years) participated in this study. Electromyographic (EMG) activities of the
      right masseter and bilateral suprahyoid muscles were recorded during sleep with
      and without a bionator. Although no significant changes were observed in the
      maximal EMG activities of these muscles, the maximal EMG activity of suprahyoid
      muscles tended to decrease while wearing the bionator. The number of events over
      40% maximal voluntary contraction (MVC) tended to decrease in these muscles with
      a bionator, but these changes were not statistically significant. These findings
      indicate that there are no significant changes or there is only a tendency to
      decrease the activities of the masseter and suprahyoid muscles while wearing a
      bionator during sleep.

PMID- 11843274
TI  - Comparative long term post-treatment changes in hyperdivergent Class II Division
      1 patients with early cervical traction treatment.
AB  - This was a retrospective study of 45 Class II Division I hyperdivergent patients
      treated in the mixed dentition with cervical traction and an incisor biteplane.
      The interjaw or "B" angle (mandibular plane to palatal plane angle) was used to
      determine hyperdivergency. The treated sample was subdivided into 2 groups
      reflecting whether the mandibular or palatal plane contributed the greatest
      amount to the more than 1 standard deviation of the "B" angle from the mean value
      of the "B" angle present in the 89 untreated Class I controls. Complete records
      including lateral cephalometric head films were acquired at the start of
      treatment and 18 to 91 months after discontinuing all retention. Null hypotheses
      were designed to determine if any significant changes in the "B" angle,
      mandibular plane angle, or palatal plane angle occurred in the control group or
      the treated group. Thirty-two angular, linear, and proportional data were
      accumulated to determine the presence or absence of significant differences. The
      only significant angular differences found were in the group in which the palatal
      plane inclination was increased relative to Frankfort Horizontal. In this group,
      the palatal plane became more nearly parallel to Frankfort Horizontal than in the
      control group, and showed an increase instead of a decrease in the Y-axis.
      Proportional and linear data indicated the palatal plane change was a lack of
      descent of Posterior Nasal Spine while the descent of Anterior Nasal Spine was
      equal to that of the control group. The increase in the Y-axis was not the result
      of bite opening, but a lack of mandibular horizontal development as indicated by
      less of an increase in the Facial Angle. Of the 45 patients, only 4 (9%) required
      2 phases of treatment and 1 of those required extraction. Thirty patients (67%)
      completed treatment with alignment and retraction of the maxillary anterior
      segment and 11 (24%) had additional alignment of the mandibular anterior segment.

PMID- 11843275
TI  - A cephalometric analysis of patients with recessive dystrophic epidermolysis
      bullosa.
AB  - Patients diagnosed with Recessive Dystrophic Epidermolysis Bullosa (RDEB) suffer
      from severe growth inhibition due to reduced food intake as a result of severe
      oropharyngeal and esophageal blistering. This investigation examined the patterns
      of facial growth in a group of 42 children with RDEB for whom lateral skull
      radiographs were available. The differences between RDEB patients and patients
      with normal cephalometric values were also assessed. Lateral skull radiographs
      were digitized and a number of orthodontic indices were compared to the published
      normal values. The RDEB patients examined demonstrated smaller maxillae than
      normal (length 41.3 +/- 2.9 mm compared to 47.4 +/- 2.5 mm) and smaller mandibles
      than normal (length 82.3 +/- 6.1 mm compared to 93.1 +/- 4.2 mm). This impaired
      growth may result from reduced food intake or severe orofacial scarring
      associated with RDEB. This contributes significantly to dento-alveolar
      disproportion and dental crowding and puts patients at increased risk of dental
      caries.

PMID- 11843276
TI  - Effects of a modified acrylic bonded rapid maxillary expansion appliance and
      vertical chin cap on dentofacial structures.
AB  - The aim of this study was to determine the sagittal, transverse, and vertical
      effects of a modified acrylic bonded rapid maxillary expansion (RME) device used
      with a vertical chin cap on dentofacial structures. The study group consisted of
      34 patients (25 girls and 9 boys) who were selected without regard to their
      skeletal class and gender. All subjects had permanent dentition (mean age, 12.7
      years) and needed maxillary expansion. Study Group I (RME only) was composed of
      17 subjects, and study Group II (RME with vertical chin cap) was composed of 17
      subjects. Twenty-nine measurements were made on the patients' cephalometric films
      and plaster models. The means and standard deviations for linear and angular
      cephalometric measurements were analyzed statistically, and intra-group and inter
      group changes were evaluated by paired and Student's t-tests using SPSS 10.1 for
      windows. We found that the maxilla moved anteriorly relative to the anterior
      cranial base. The nasal width, maxillary width, intercanine width, mandibular
      intermolar width, maxillary intermolar width, and overjet all increased, while
      the upper molars tipped buccally in both groups. In Group I, the mandible rotated
      posteriorly, the lower anterior facial height increased, and the overbite
      decreased. These effects were reduced in Group II. We conclude that the vertical
      chin cap is an effective appliance for preventing the adverse vertical effects of
      RME in patients with a crossbite and a vertical growth pattern.

PMID- 11843277
TI  - Ethnic differences in the soft tissue profile of Korean and European-American
      adults with normal occlusions and well-balanced faces.
AB  - Orthodontic diagnosis typically includes comparing a patient's cephalometric
      measurements to standard values. Lateral cephalometric norms, however, may be
      specific to an ethnic group and cannot always be applied to other ethnic types.
      The purpose of this study was to compare the soft tissue profiles obtained from
      Korean and European-American adults with normal occlusions and well-balanced
      faces, in order to understand the ethnic differences in the soft tissue profile
      between these two ethnic groups. The lateral cephalograms of 60 Korean (30 men
      and 30 women) and 42 European-American adults (15 men and 27 women) were traced
      and digitized by one investigator. Ten angular measurements of facial form and
      seven linear and angular measurements of lip position were computed. A comparison
      of the slope of the forehead showed no significant differences between the two
      groups. The Korean sample, however, had a lower angle of nasal inclination and a
      higher degree of lip protrusion compared to the European-American adults. Chin
      protrusion of the Koreans was less prominent than that of the European-Americans.
      These differences between ethnic groups should be taken into consideration when
      formulating an orthodontic treatment plan for patients of varying ethnic
      backgrounds.

PMID- 11843279
TI  - Current challenges and future dilemmas facing the orthodontic profession.
      Proceedings of a Workshop, The College of Diplomates of the American Board of
      Orthodontics. Sun Valley, Idaho, July 21-25, 2001.

PMID- 11843278
TI  - Three-dimensional magnetic resonance image of the mandible and masticatory
      muscles in a case of juvenile chronic arthritis treated with the Herbst
      appliance.
AB  - The present report documents, in a case of juvenile chronic arthritis (JCA) with
      mandibular retrognathia, three-dimensional (3D) changes in the mandible and the
      relationship between the mandible and the masticatory muscles resulting from
      treatment with the Herbst appliance after cessation of growth. Magnetic resonance
      scanning of the whole head was carried out before and after treatment. The
      mandible, the masseter, and the medial and lateral pterygoid muscles were
      segmented bilaterally and reconstructed in 3D for both stages. Superimposition of
      the datasets was carried out according to anatomical structures in the brain
      (cranial base). Mandibular superimposition was performed according to the
      mandibular symphysis and the lower mandibular border. The mandible moved forward
      and downward relative to the anterior cranial base. In addition, bone apposition
      was observed at the superior and posterior surfaces of both mandibular condyles
      and at the roof of the glenoid fossa. The masticatory muscles remained relatively
      stable in position in relation to the anterior cranial base. To our knowledge,
      such information in JCA patients has not previously been published in the
      literature. Using magnetic resonance imaging (MRI), it was possible to gain
      improved insight into the 3D morphology including soft tissues without the
      overlap of the surrounding tissues observed in the conventional radiographs.
      Accordingly, it is suggested that 3D magnetic resonance analysis is a more useful
      method for the follow-up of the JCA patients than radiographic techniques.

PMID- 11843281
TI  - Successful unrelated bone marrow transplantation after arsenic trioxide treatment
      in a patient with relapsed acute promyelocytic leukemia.

PMID- 11843280
TI  - Superior mesenteric venous thrombosis associated with a familial missense
      mutation (Pro626Leu) in the SHBG-like domain of the protein S molecule.
AB  - A 76-year-old Japanese woman was hospitalized for ileus symptoms caused by
      extensive thrombosis of the superior mesenteric vein. Because laboratory test
      results suggested type III protein S (PS) deficiency, molecular changes in PS
      were investigated. A single-base transition, CCG to CTG at codon 626 in exon XV,
      resulting in the missense mutation Pro626Leu, was identified in an allele of the
      patient and in her son. Reverse transcriptase polymerase chain reaction analysis
      indicated the presence of both normal and mutant types of PS messages in platelet
      derived messenger RNAs. Our findings thus suggest that Pro626 in SHBG-like domain
      7 may be crucial for in vivo antithrombotic activity of the PS molecule.

PMID- 11843282
TI  - Secondary acute promyelocytic leukemia in a patient with non-Hodgkin's lymphoma
      treated with VP-16 and MST-16.

PMID- 11843283
TI  - Thrombopoietin in human milk.

PMID- 11843284
TI  - Toxoplasmic encephalitis in a non-HIV patient with follicular lymphoma.

PMID- 11843285
TI  - Functional property of von Willebrand factor under flowing blood.
AB  - von Willebrand factor (vWF) is produced in megakaryocytes and endothelial cells,
      is stored in the alpha-granule of platelets and in the Weibel-Palade body of
      endothelial cells, and is present in plasma and vascular subendothelium. This
      huge protein with a unique multimeric structure plays a pivotal role in both
      hemostasis and pathological intravascular thrombosis, in which vWF contributes to
      both platelet adhesion/aggregation and blood coagulation through its multiple
      adhesive functions for the platelet membrane receptors, glycoprotein Ib-IX-V
      complex, integrin alphaIIbbeta3, heparin, various types of collagen, and
      coagulation factor VIII. Among various functions, the most characteristic feature
      of vWF is its determinant role on platelet thrombus formation under high-shear
      rate conditions. Indeed, at in vivo rheological situations where platelets are
      flowing with high speed in the bloodstream, the only reaction that can initiate
      mural thrombogenesis is the interaction of vWF with platelet glycoprotein
      Ibalpha. The recent x-ray analysis of the crystal structure of various functional
      domains and functional studies of this protein under experimental flow conditions
      have rapidly advanced and revised our knowledge of the structure-function
      relationships of vWF, a key protein for hemostasis and arterial thrombosis.

PMID- 11843287
TI  - Molecular and cellular biology of von Willebrand factor.
AB  - von Willebrand factor (VWF) is a plasma protein that performs 2 main functions in
      hemostasis: it mediates platelet adhesion to the injured vessel wall, and it
      carries and protects coagulation factor VIII. VWF is synthesized through a
      multistep process in endothelial cells and megakaryocytes as a very large polymer
      composed of identical disulfide-linked 250-kd subunits. In endothelial cells, VWF
      not only directs the formation of its own storage granules, the Weibel-Palade
      bodies, but it also acts as a chaperone molecule to direct other proteins, such
      as P-selectin, into these granules. Upon stimulation of the endothelium, the
      Weibel-Palade bodies will be translocated to the plasma membrane, and their
      contents will be secreted into the plasma milieu. The expression of VWF can be
      regulated at different levels by a number of genetic and environmental factors,
      resulting in control of its activity. New roles for VWF, especially in
      inflammatory processes, have recently been suggested, indicating that some
      aspects of this well-studied protein remain to be investigated.

PMID- 11843286
TI  - Von Willebrand factor-cleaving protease and Upshaw-Schulman syndrome.
AB  - Vascular endothelial cell (EC)-produced plasma von Willebrand factor (vWF) plays
      a critical role in primary hemostasis through its action of anchoring platelets
      onto the injured denuded subendothelial matrices under high shear stress.
      Unusually large vWF multimers (UL-vWFMs), present in plasma immediately after
      release from ECs, are most biologically active, but they are soon cleaved and
      degraded into smaller vWFMs by a specific plasma protease, termed vWF-cleaving
      protease (vWF-CPase), in normal circulation. Recent studies on the relationship
      between UL-vWFMs and vWF-CPase, together with its autoantibody (inhibitor) have
      brought about a clear discrimination between thrombotic thrombocytopenic purpura
      and hemolytic uremic syndrome. Furthermore, a congenital deficiency of this
      enzyme activity has been shown to cause Upshaw-Schulman syndrome, a complex
      constitutional bleeding diathesis. Successful purification of vWF-CPase revealed
      that this enzyme is composed of a single polypeptide with a molecular mass of
      approximately 190 kd, and its complementary DNA cloning unambiguously indicated
      that it is uniquely produced in the liver and its gene is located on chromosome
      9q34. The messenger RNA of vWF-CPase had a span of 4.6 kb, and its enzyme was
      designated ADAMTS 13. The predicted complete amino acid sequence of this enzyme
      consisted of 1427 residues, including a signal peptide, a short propeptide
      terminating in the sequence RQRR, a reprolysin-like metalloprotease domain, a
      disintegrin-like domain, a thrombospondin-1 repeat (TSP1), a cysteine-rich
      domain, an ADAMTS spacer, 7 additional TSP1 repeats, and 2 CUB domains.

PMID- 11843288
TI  - Triple heterozygosity of a hemoglobin variant: hemoglobin Pyrgos with other
      hemoglobinopathies.
AB  - This article is the first report of hemoglobin (Hb) Pyrgos along with other Hbs
      forming triple-heterozvgous patterns. Of 2 cases, the first occurred in a Thai
      girl with thalassemic facies, marked anemia, and hepatosplenomegaly, who had Hb
      Pyrgos in association with Hb H disease with Hb Constant Spring (CS). This case
      represents a triple heterozygosity comprising Hb Pyrgos, alpha-thalassemia 1, and
      Hb CS. Hb electrophoresis revealed an abnormal Hb in addition to Hbs CS, A2, A,
      Bart's, and H. This abnormal Hb moved slightly faster than Hb A but more slowly
      than Hb Bart's. Polymerase chain reaction revealed that the abnormal Hb was
      caused by a missense mutation within codon 83 of the beta-globin gene (GGC to
      GAC) resulting in a glycine-to-aspartic acid substitution, which corresponds to
      Hb Pyrgos. The patient required blood transfusions by the age of 3 years. A
      splenectomy was performed when she was 5 years old, after which her hematocrit
      level remained above 32%. The second case was the patient's older sister who was
      also triple heterozygous (Hb Pyrgos, E, and CS) but was healthy.

PMID- 11843289
TI  - Detection of CD55- and/or CD59-deficient red cell populations in patients with
      plasma cell dyscrasias.
AB  - Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal disorder
      characterized by a decrease or absence of glycosylphosphatidylinositol (GPI)
      anchored molecules such as CD55 and CD59 from the surface of affected cells,
      resulting in intravascular hemolysis, cytopenia, and venous thrombosis. A PNH
      like phenotype has been detected in various hematological disorders, mainly in
      aplastic anemia and myelodysplastic syndromes, but also in lymphoproliferative
      syndromes (LPSs). To the best of our knowledge, CD55- or CD59-deficient red cells
      have not been detected in plasma cell dyscrasias (PCDs). The aim of this study
      was the detection of CD55- and/or CD59-deficient red cell populations in patients
      with PCD. Seventy-seven patients were evaluated; 62 with multiple myeloma (MM), 7
      with Waldenstrom macroglobulinemia (WM), 6 with monoclonal gammopathy of
      undetermined significance (MGUS), and 2 with heavy chain disease (HCD). The
      sephacryl gel microtyping system was applied; Ham and sucrose lysis tests were
      also performed on all samples with CD55- or CD59-negative populations. Red cells
      deficient in both molecules were detected in 10 (12.9%) of 77 patients with PCD:
      2 (28.6%) of 7 with WM, 1 (16.6%) of 6 with MGUS, 6 (9.6%) of 62 with MM, and 1
      of 2 patients with HCD. Isolated CD55 deficiency was found in 28.5% of all PCD
      patients, whereas isolated CD59 deficiency was not observed in any patients.
      These findings illustrate the existence of the PNH phenotype in the red cells of
      patients with PCD; further investigation is needed into the mechanisms and
      significance of this phenotype.

PMID- 11843290
TI  - Prognosis of elderly patients with acute myelogenous leukemia: analysis of 126
      AML cases.
AB  - We retrospectively analyzed 126 acute myelogenous leukemia (AML) patients aged >
      or =60 years who had all been referred to the same hematological department
      between 1989 and 1999. In 76 de novo AML cases, 53 patients (median age, 72
      years) were treated with combination chemotherapy (CT) for remission induction.
      Complete remission (CR) rate was 57.1%. The median overall survival (OS) was 16
      months, and the rate of 3-year OS was 28%. The favorable prognostic factors were
      performance status < or =2, cholinesterase > or =100 IU, and intermediate or
      favorable karyotype (P < .01). Seventeen patients (median age, 78 years) with
      hypocellular bone marrow or poor general condition were treated with low-dose
      cytosine arabinoside (LDAraC). In these patients, the CR rate was 50% and the
      median OS was 11 months, with an OS estimate at 3 years of 14%. All patients with
      hypocellular bone marrow who received LDAraC for 21 days achieved CR. In 50
      patients who developed AML following a myelodysplastic syndrome (MDS/AML), 22
      patients (median age, 74 years) were treated with CT, and 14 (median age, 74
      years) patients were treated with LDAraC. The CR rates were 22.7% and 21.4%,
      respectively, and the median OS durations were 8 months and 11 months,
      respectively. There were no significant factors that would indicate a good
      prognosis in MDS/AML patients.

PMID- 11843291
TI  - Constitutive activation of Stat1 and Stat3 in primary erythroleukemia cells.
AB  - Signal transducers and activators of transcription (Stat) proteins play important
      roles in the regulation of hematopoiesis as downstream molecules of cytokine
      signal transduction. Previously, we demonstrated that Stat1 and Stat3 are
      activated by erythropoietin (EPO) in a human EPO-dependent erythroleukemia cell
      line UT-7/EPO. We report here that Stat1 and Stat3 are constitutively activated
      in freshly isolated erythroleukemia cells. In addition, EPO promoted cell growth
      of these cells, accompanied by enhanced activities of Stat1 and Stat3.
      Furthermore, mutation in the Statl/Stat3-binding sites of the c-myc gene promoter
      clearly blocked its promoter activity in EPO-stimulated primary erythroleukemia
      cells. Thus, Stat1 and Stat3 may support cell growth in part via c-myc gene
      activation in primary erythroleukemia cells.

PMID- 11843294
TI  - Therapy-related myelodysplastic syndrome in a case of cutaneous adult T-cell
      lymphoma.
AB  - We report a case of therapy-related myelodysplastic syndrome (t-MDS) in adult T
      cell lymphoma. A 69-year-old man suffered from cutaneous adult T-cell lymphoma,
      which was treated with radiation to the skin and combination chemotherapy of CHOP
      V-MMV and VEPA-B. After 14 months of these therapies, anemia and thrombocytopenia
      appeared, and bone marrow aspiration smears showed immature myeloblasts,
      dysplastic erythroblasts, and micromegakaryocytes. Therapy-related MDS of
      refractory anemia with an excess of blasts was diagnosed. Cytogenetic study of
      the bone marrow cells showed 5q- and additional abnormalities. Rearrangement of
      the MLL gene was observed in the bone marrow cells. Mutations of N-ras codons at
      12,13, and 61, p53 tumor suppressor gene, and monoclonal integration of human T
      lymphotrophic virus -1 provirus DNA were not observed in the bone marrow cells.
      The patient died of pneumonia 21 months after diagnosis of cutaneous adult T-cell
      lymphoma.

PMID- 11843293
TI  - Philadelphia chromosome-positive acute myeloid leukemia with tetraploidy.
AB  - The patient was a 62-year-old man. His hematological data in April 2000 had shown
      no abnormalities, but he was referred to our hospital because of a fever and
      leukocytosis in June 2000. The peripheral blood showed 29.8 x 10(9)/L white blood
      cells, with 68.0% blasts. A bone marrow aspirate showed hypercellularity with a
      proliferation of large leukemic blasts. The leukemic cells were positive for CD13
      (91%), CD33 (54.8%), CD34 (94.5%), and HLA-DR (97.9%). Some leukemic cells
      (15.6%) also expressed CD14. Cytogenetic analysis revealed
      92,XXYY,t(9;22)(q34;q11)x2 in all 20 metaphase cells. Reverse transcriptase
      polymerase chain reaction analysis detected the minor BCR/ABL messenger RNA
      (mRNA) but failed to detect the major BCR/ABL mRNA. The patient achieved complete
      remission after induction chemotherapy, with no evidence of Philadelphia
      chromosome (Ph) or minor BCR/ABL mRNA. Ph-positive acute myeloid leukemia (Ph
      AML) has rarely been reported. Herein, we report a case of Ph-AML with
      tetraploidy and review the previously reported Ph-AML cases.

PMID- 11843292
TI  - The generation of immunocompetent dendritic cells from CD34+ acute myeloid or
      lymphoid leukemia cells.
AB  - The ability of CD34+ leukemic cells to differentiate to dendritic cells (DCs) was
      investigated in 18 acute myeloid leukemia (AML) and 4 lymphoid leukemia (ALL)
      patients. The generation of DCs was determined by the expression of DC-associated
      CD1a or CD83 (more than 30%) with costimulatory molecules, by CD80 antigens
      (>20%), and by the exhibition of allostimulatory activity. In the AML patients,
      allostimulatory mature DCs were generated from 3 of 9 M0 or M1, 2 of 5 M2,2 of 4
      M4 or M5, and 3 of 4 ALL (L2) cases. In total, DCs were more efficiently induced
      from cases expressing over 75% of CD34+ among whole bone marrow mononuclear cells
      (8 of 12), compared with those under 75% (2 of 10; P < .05). B-cell (CD19),
      natural killer (NK)-cell (CD56), or T-cell (CD7) lineage markers, which were
      aberrantly expressed on the blasts, were rarely found on leukemic DCs at the end
      of the culture period, and myeloid (CD13, CD33), not lymphoid (CD10), markers
      were shown on ALL-derived DCs. In Philadelphia chromosome-positive ALL or AML
      patients with t (8;21), DCs were confirmed to be of leukemic origin by
      fluorescence in situ hybridization analysis.

PMID- 11843295
TI  - Establishment of a monosomy 7 leukemia cell line, MONO-7, with a ras gene
      mutation.
AB  - A monosomy 7 leukemia cell line, designated MONO-7, was established from the
      peripheral blood of a patient with monosomy 7 acute myelocytic leukemia (French
      American-British classification M0). The cells were cultured continuously for
      more than 24 months in RPMI-1640 medium supplemented with 10% heat-inactivated
      fetal calf serum. The cell line exhibits an unclassified appearance.
      Cytochemically, alpha-naphthol-acetate esterase and myeloperoxidase are negative.
      Immunophenotypically, the cell line expresses CD33, CD13, CD56, CD34, CD38, HLA
      DR, and CD45, but lacks T and B cell-associated antigens. Karyotypic analysis of
      the cell line showed only 45,XY,-7. Analysis of the N-ras gene mutation
      demonstrated identical mutations in fresh leukemic cells and the MONO-7 cell
      line. Clonal rearrangements of the immunoglobulin heavy-chain gene, T-cell
      receptor beta-chain gene, or T-cell receptor gamma-chain gene were not found in
      DNA extracted from MONO-7 cells. The growth of MONO-7 cells in vitro was
      stimulated by recombinant human granulocyte-macrophage colony-stimulating factor
      or interleukin 3. To our knowledge, this is the first report of the establishment
      of a cell line with the karyotype 45,XY,-7 without any other abnormality and with
      a ras gene mutation.

PMID- 11843296
TI  - Detection of Epstein-Barr virus and human T-cell lymphotropic virus type 1 in
      malignant nodal lymphoma, studied in Okinawa, a subtropical area in Japan.
AB  - Formalin-fixed paraffin-embedded lymph node samples were collected from 100 cases
      of malignant nodal lymphoma documented in Okinawa in the period from 1973 through
      1998. According to the new World Health Organization classification, 12 cases
      were Hodgkin's lymphoma (HL). Eighty-eight cases of non-Hodgkin's lymphoma (NHL)
      included 54 cases of T-cell type and 34 cases of B-cell type. Using polymerase
      chain reaction (PCR), Epstein-Barr virus (EBV) was detected in 11 cases (91.7%)
      of HL and in 57 cases (64.8%) of NHL, and human T-cell lymphotropic virus type 1
      (HTLV-1) was detected in 23 cases (26.1%) of NHL. Clonal integration of HTLV-1
      was detected in 10 (43.5%) of 23 HTLV-1 PCR-positive cases by the inverse PCR
      technique. The EBV-infected cells were detected by EBER-1 in situ hybridization
      in 11 (91.7%) of 12 HL cases and in 64 (72.7%) of 88 NHL cases. Irrespective of
      phenotype and tissue type of the malignant lymphoma, the rate of EBV-positive
      infection in Okinawa was higher than that in any other districts reported in
      Japan. This characteristic high rate of EBV-positive infection in Okinawa can be
      ascribed to various factors, such as racial and geographical differences.

PMID- 11843297
TI  - Primary hepatic low-grade B-cell lymphoma of the mucosa-associated lymphoid
      tissue type: a case report and review of the literature.
AB  - Primary hepatic lymphoma, mostly diffuse large B-cell lymphoma, is a rare
      disease. We describe an extremely rare case of low-grade B-cell lymphoma of the
      mucosa-associated lymphoid tissue (MALT) type occurring in the liver. A 61-year
      old man with a history of hepatitis A presented with early gastric cancer and a
      liver mass. Needle biopsy of the liver tumor suggested low-grade B-cell lymphoma
      by histology and polymerase chain reaction of the immunoglobulin heavy chain
      gene. The tumor (3.4 x 2.8 x 2.4 cm) was completely resected from the anterior
      segment of the right lobe of the liver. Atypical lymphoid cells of small to
      intermediate size proliferated in the tumor, and lymphoepithelial lesions were
      recognized. Immunohistochemically, lymphoma cells were positive for CD20 and
      negative for CD5, CD10, and cyclin D1. Staging procedures showed no lymphoma
      lesion other than the liver tumor. Thus, the patient was diagnosed with low-grade
      hepatic marginal zone B-cell lymphoma of the MALT type. The patient has been
      followed up for 1.5 years since surgical resection with no recurrence. The
      clinicopathologic characteristics and management of this rare disease are
      discussed.

PMID- 11843299
TI  - Plasma thrombopoietin in patients with cavernous transformation of the portal
      vein.
AB  - Thrombopoietin (TPO), the primary regulator of thrombopoiesis, is produced mainly
      in the liver. Previous studies investigating blood TPO in chronic liver diseases
      revealed conflicting results. It has been suggested that hepatic TPO production
      is regulated by the portal blood supply to the liver. However, the role of TPO in
      the pathobiological basis of idiopathic portal vein thrombosis (PVT) and
      cavernous transformation of the portal vein (CTPV) has not been elucidated. The
      objective of this study is to assess plasma TPO concentrations in patients with
      CTPV. Eleven patients (4 men and 7 women, aged 38+/-12 years) with CTPV were
      studied. Sixteen healthy adults served as the control group (8 men and 8 women,
      aged 34+/-12 years). Median plasma TPO concentration was 326 pg/mL (range, 15
      1402 pg/mL) in the patients with CTPV and 62.65 pg/mL (range, 38.5-102 pg/mL) in
      the control group (P = .003). In this study, we found significantly higher TPO
      concentrations in the plasma of patients with CTPV. The higher concentrations
      could be a result of the altered portal hemodynamics due to thrombosis. Moreover,
      TPO release by activated platelets might lead to the subsequent propagation of
      thrombosis in PVT.

PMID- 11843300
TI  - Successful use of recombinant factor VIIa for hemostasis during total knee
      replacement in a severe hemophiliac with high-titer factor VIII inhibitor.
AB  - A 32-year-old male patient with severe factor VIII (FVIII) deficiency had
      developed a high-titer FVIII inhibitor at age 13. Recurrent hemarthroses caused
      bony destruction in both knees, significantly impairing his ability to walk. Knee
      examination revealed 20 degrees of varus, destruction of the medial joint line,
      and flexion contracture. Total knee arthroplasty was performed using recombinant
      factor VIIa (rFVIIa, NovoSeven) for hemostatic control. rFVIIa (85 microg/kg
      given intravenously over 3-5 minutes) was given just prior to surgery. The dose
      was repeated every 2 hours during and for the first 48 hours after surgery. When
      the tourniquet was removed, rFVIIa had not been infused for 1.5 hours, and
      significant hemorrhage was noted. The hemorrhage responded promptly to rFVIIa
      infusion. The infusion interval was extended to every 4 hours for an additional
      48 hours, and subsequent doses were given every 6 hours until the patient
      returned to the clinic 2 days postdischarge. Hemoglobin levels dropped from 16.9
      gm/dL on admission to 9.1 gm/dL at discharge. After 2 months, the patient
      returned to work. We recommend that tourniquet release be performed immediately
      after rFVIIa administration and that aggressive physical therapy be considered in
      the early postoperative period when rFVIIa infusions are frequent.

PMID- 11843298
TI  - Molecular genetics of type 2 von Willebrand disease.
AB  - Type 2 von Willebrand disease (VWD) is characterized by a wide heterogeneity of
      functional and structural defects. These abnormalities' cause either defective
      von Willebrand factor (VWF)-dependent platelet function in subtypes 2A, 2B, and
      2M or defective VWF-factor VIII (FVIII) binding in subtype 2N. The diagnoses of
      types 2A, 2B, and 2M VWD may be guided by the observation of disproportionately
      low levels of ristocetin cofactor activity or collagen-binding capacity relative
      to VWF antigen. The abnormal platelet-dependent function is often associated with
      the absence of high molecular weight (HMW) multimers (type 2A, type 2B), but the
      HMW multimers may also be present (type 2M, some type 2B), and supranormal
      multimers may exist ("Vicenza" variant). The observation of a low FVIII-to-VWF:Ag
      ratio is a hallmark of type 2N VWD. in which the FVIII levels depend on the
      severity of the FVIII-binding defect. Today, the identification of mutations in
      particular domains of the pre-pro-VWF is helpful in classifying these variants
      and providing further insight into the structure-function relationship and the
      biosynthesis of VWF. Thus, mutations in the D2 domain, involved in the
      multimerization process, are found in patients with type 2A, formerly named IIC
      VWD. Mutations located in the D' domain or in the N terminus of the D3 domain
      define type 2N VWD. Mutations in the D3 domain characterize Vicenza and IIE
      patients. Mutations in the A1 domain may modify the binding of VWF multimers to
      platelets, either increasing (type 2B) or decreasing (type 2M, 2A/2M) the
      affinity of VWF for platelets. In type 2A VWD, molecular abnormalities identified
      in the A2 domain, which contains a specific proteolytic site, are associated with
      alterations in folding, impairing VWF secretion or increasing its susceptibility
      to proteolysis. Finally, a mutation localized in the carboxy-terminus CK domain,
      which is crucial for the dimerization of the VWF subunit, has been identified in
      a rare subtype 2A, formerly named IID.

PMID- 11843301
TI  - Root, root hair, and symbiotic mutants of the model legume Lotus japonicus.
AB  - To gain an overview of plant factors controlling nodule number and organogenesis,
      an extensive screening using model legume Lotus japonicus was carried out. This
      screening involved 40,000 M2 seeds, and 32 stable mutant lines were isolated.
      From these, 16 mutant lines maintaining the phenotypic variation were selected
      and genetically analyzed. With respect to nodule number, four loci were
      identified, Ljsym77, Ljsym78, slippery root (slp), and radial organization1
      (rdo1). The former two mutants have an increased number of nodules, while the
      latter two have a decreased number. Ljsym78-1 and Ljsym78-2 are hypernodulating
      mutants with a branched root system and were found to be allelic to Ljsym16. The
      phenotype of the Ljsym77 mutant was highly pleiotropic, being deficient in light
      and gravity responses. The slp mutant was isolated as a low-nodulating mutant
      lacking root hairs. Concerning nodule organogenesis, nine symbiotic loci were
      identified, including the two loci alb1 and fen1. Mutants affecting the
      developmental process of nodule organogenesis were placed in three phenotypic
      categories: Nod- (Ljsym70 to Ljsym73), Hist- (alb1-1, alb1-2, and Ljsym79), and
      Fix- (fen1, Ljsym75, and Ljsym81).

PMID- 11843302
TI  - Characterization of the salA, syrF, and syrG regulatory genes located at the
      right border of the syringomycin gene cluster of Pseudomonas syringae pv.
      syringae.
AB  - Sequence analysis of the right border of the syr gene cluster of Pseudomonas
      syringae pv. syringae strain B301D revealed the presence of the salA gene 8,113
      bp downstream of syrE. The predicted SalA protein of strain B301D differs by one
      amino acid from that of strain B728a. Two homologs of salA, designated syrF and
      syrG, were identified between syrE and salA. All three proteins contain helix
      turn-helix DNA-binding motifs at their C termini and exhibit homology to
      regulatory proteins of the LuxR family. A salA mutant failed to produce
      syringomycin, whereas syrF and syrG mutants produced 12 and 50%, respectively, of
      syringomycin relative to the wild-type strain. The salA, syrF, and syrG mutants
      were significantly reduced in virulence, forming small, nonspreading lesions in
      immature cherry fruits. Translational fusions to the uidA gene were constructed
      to evaluate expression of syrB1 in regulatory mutant backgrounds and to determine
      the relationship among the three regulatory loci. Expression of a syrB1::uidA
      fusion required functional salA and syrF genes and, in series, the expression of
      a syrF::uidA fusion required a functional salA gene. These results demonstrate
      that salA is located upstream of syrF in the regulatory hierarchy controlling
      syringomycin production and virulence in P. syringae pv. syringae.

PMID- 11843303
TI  - MucR and mucS activate exp genes transcription and galactoglucan production in
      Sinorhizobium meliloti EFB1.
AB  - When grown under standard conditions, Sinorhizobium meliloti EFB1 simultaneously
      produces two acidic exopolysaccharides, succinoglycan and galactoglucan, yielding
      very mucoid colonies. In this strain, MucR is essential for galactoglucan
      synthesis. A mutation in the mucS gene resulted in less mucoid colonies than in
      the wild-type EFB1. This mucS- strain was complemented to the wild-type phenotype
      by the cloned mucS gene, indicating that mucS is necessary for a wild-type level
      of galactoglucan production. Reverse transcription-polymerase chain reaction
      analysis of exp genes, which encode the pathway for galactoglucan production, in
      EFB1 and in the mutants affected in mucS, mucR, and both genes simultaneously,
      showed that MucS is a transcriptional activator of the exp genes but does not
      affect its own transcription. Furthermore, MucR is necessary for mucS
      transcriptional activation. As introduction of a cloned mucS gene in a mucR-
      strain yielded colonies less mucoid than the wild type, MucR could also activate
      exp genes transcription through other pathways. Deletion analysis of the expE
      promoter showed a region important for transcription and MucS activation. This
      region, containing a palindrome, is present in the putative expA, expC, expD, and
      expE promoters but not in the mucS promoter, suggesting that it is the target for
      MucS. A mucR-mucS- mutant, which does not produce galactoglucan, was impaired in
      competitive nodulation of alfalfa in soil microcosms, indicating another possible
      role for this exopolysaccharide in symbiosis.

PMID- 11843304
TI  - Analysis of the structure of the AVR1-CO39 avirulence locus in virulent rice
      infecting isolates of Magnaporthe grisea.
AB  - The AVR1-CO39 gene that came from a Magnaporthe grisea isolate from weeping
      lovegrass controls avirulence on the rice cultivar CO39. AVR1-CO39 was not
      present in the genome of the rice-infecting M. grisea isolate Guyll from French
      Guyana, suggesting that the gene had been deleted. Molecular analysis of the
      deletion breakpoints in the AVR1-CO39 locus revealed the presence of a truncated
      copy of a previously unknown retrotransposon at the left-hand border. At the
      right-hand border was a truncated copy of another repetitive element that is
      present at multiple locations in the genome of Guyll. The structures of avr1-CO39
      loci were further examined in 45 rice-infecting isolates collected in Brazil,
      China, Japan, India, Indonesia, Mali, and the Philippines. Most isolates showed
      no hybridization signal with the AVR1-CO39 probe and had the same locus structure
      as Guyll. Some isolates from Japan showed a signal with the AVR1-CO39 probe, but
      the region specifying avirulence activity was rearranged. These findings suggest
      that widespread virulence to 'CO39' among rice-infecting M. grisea isolates is
      due to ancestral rearrangements at the AVR1-CO39 locus that may have occurred
      early in the evolution of pathogenicity to rice.

PMID- 11843305
TI  - Competitive nodulation blocking of cv. Afghanistan pea is related to high levels
      of nodulation factors made by some strains of Rhizobium leguminosarum bv. viciae.
AB  - Cultivar Afghanistan peas are resistant to nodulation by many strains of
      Rhizobium leguminosarum bv. viciae but are nodulated by strain TOM, which carries
      the host specificity gene nodX. Some strains that lack nodX can inhibit
      nodulation of cv. Afghanistan by strain TOM. We present evidence that this
      "competitive nodulation-blocking" (Cnb) phenotype may result from high levels of
      Nod factors inhibiting nodulation of cv. Afghanistan peas. The TOM nod gene
      region (including nodX) is cloned on pIJ1095, and strains (including TOM itself)
      carrying pIJ1095 nodulate cv. Afghanistan peas very poorly but can nodulate other
      varieties normally. The presence of pIJ1095, which causes increased levels of Nod
      factor production, correlates with Cnb. Nodulation of cv. Afghanistan by TOM is
      also inhibited by a cloned nodD gene that increases nod gene expression and Nod
      factor production. Nodulation of cv. Afghanistan can be stimulated if nodD on
      pIJ1095 is mutated, thus severely reducing the level of Nod factor produced.
      Repression of nod gene expression by nolR eliminates the Cnb phenotype and can
      stimulate nodulation of cv. Afghanistan. Addition of Nod factors to cv.
      Afghanistan roots strongly inhibits nodulation. The Cnb+ strains and added Nod
      factors inhibit infection thread initiation by strain TOM. The sym2A allele
      determines resistance of cv. Afghanistan to nodulation by strains of R.
      leguminosarum bv. viciae lacking nodX. We tested whether sym2A is involved in Cnb
      by using a pea line carrying the sym2A region introgressed from cv. Afghanistan;
      nodulation in the introgressed line was inhibited by Cnb+ strains. Therefore, the
      sym2A region has an effect on Cnb, although another locus (or loci) may
      contribute to the stronger Cnb seen in cv. Afghanistan.

PMID- 11843306
TI  - How to reduce smoking among teenagers.

PMID- 11843307
TI  - Lymphocyte activation after exposure to swine dust: a role of humoral mediators
      and phagocytic cells.
AB  - Exposure to swine dust causes intense airway inflammation with multifold increase
      in inflammatory cells and secretion of pro-inflammatory cytokines. This in vitro
      study focuses on the swine-dust activation of lymphocytes in whole blood, in
      phagocyte-depleted whole blood and in peripheral blood mononuclear cells (PBMC),
      in order to investigate whether phagocytic cells and/or soluble mediators are
      involved in the activation of T-cells following exposure to organic dust from a
      swine confinement house. T-cell activation was analysed by flow cytometry with
      double staining for CD3 and the activation marker CD69. Swine dust (50 microg)
      incubated (24 h) with heparinized whole blood was shown to activate 27.6% of the
      T-cells, while swine dust incubated with whole blood depleted from phagocytic
      cells or PBMC only activated 4.5%, and 4.8% of the T-cells, respectively. Plasma
      separated from whole blood preincubated with swine dust for 24 h stimulated as
      much as 32.4% of PBMC T-cells and contained high levels of interleukin (IL)-12
      (14 pg x mL) and interferon (IFN)-gamma (2284 pg x mL(-1)), while plasma from
      PBMC incubated with swine dust contained low levels of IL-12 (2 pg x mL(-1)) and
      IFN-gamma (196 pg x mL(-1)). This study demonstrates that activation of T-cells
      by organic dust from a swine confinement building seems to require phagocytic
      cells, most likely acting through the release of soluble mediators. Also,
      conditioned plasma from swine-dust exposed whole blood, which was capable of
      activating T-cells, contained high concentrations of interleukin-12 and
      interferon-y.

PMID- 11843308
TI  - Snoring detection during auto-nasal continuous positive airway pressure.
AB  - A bench study using an artificial lung model was performed to evaluate the
      snoring detection sensitivity of six (commercially available) auto-nasal
      continuous positive airway pressure (NCPAP) devices. Snoring was simulated by a
      loudspeaker connected to the lung model and abruptly activated during 1 s of each
      inspiratory period to induce pressure oscillation. The oscillation frequencies
      chosen were 30, 60, 90, and 120 Hz. For each frequency, the amplitude of the
      pressure oscillation produced by the loudspeaker was adjusted to find the
      threshold at which the auto-nCPAP devices detected snoring. Differences in
      pressure-amplitude thresholds of up to three-fold were found across auto-nCPAP
      devices. A randomized clinical study to compare the effects of the least
      sensitive (Virtuoso LX; Respironics, Nantes, France) and one of the most
      sensitive, (Goodknight 418A; Malinckrodt, Nancy, France) devices, in two groups
      of six patients with obstructive sleep apnoea syndrome was then conducted.
      Goodknight 418A was more sensitive than Virtuoso LX for detecting snoring (mean
      +/- SD 92 +/- 11% versus 50 +/- 39% respectively, p = 0.03). To conclude,
      striking differences exist between auto-nasal continuous positive airway pressure
      devices in sensitivity for detecting snoring.

PMID- 11843309
TI  - Quality of life in patients with chronic alveolar hypoventilation.
AB  - Measurements of health-related quality of life (HRQL) have not been reported in
      patients with chronic alveolar hypoventilation (CAH) before starting home
      mechanical ventilation. The purpose of this study was to investigate quality of
      life in a population of such patients. Forty-four consecutive patients with CAH
      due to previous polio, scoliosis, healed pulmonary tuberculosis or neuromuscular
      disease answered a battery of condition specific and generic (Sickness Impact
      Profile, Hospital Anxiety and Depression scale, Mood Adjective Check List) self
      report questionnaires. Spirometry, arterial blood gases and overnight oxygen
      saturation were measured. Patients with untreated CAH had significantly impaired
      HRQL compared to historical data from a healthy reference population. Sleep
      related problems were frequent. Age, underlying disease, and standard bicarbonate
      correlated significantly with HRQL measures, albeit with modest levels of
      explained variance (8-37%). Patients with chronic alveolar hypoventilation due to
      neuromuscular or restrictive chest wall disorders had severely impaired health
      related quality of life. Age, the underlying disease and severity of
      hypoventilation are each related to the health-related quality of life
      decrements. Health-related quality of life measurements add important information
      to traditional clinical observations.

PMID- 11843310
TI  - The SleepStrip: an apnoea screener for the early detection of sleep apnoea
      syndrome.
AB  - Sleep apnoea svndrome (SAS) is a largely undiagnosed and prevalent disorder. It
      is associated with cardiovascular morbidity as well as excessive daytime
      sleepiness and poor quality of life. In the present study the SleepStrip, a novel
      screening device is introduced, which is low cost and easy to use and is aimed
      for widespread use. The results of three independent validation studies, which
      compared the SleepStrip score (Sscore) against "gold standard"
      polysomnographically-determined apnoea/ hypopnoea index (AHI), are reported both
      separately and combined. Four hundred and two patients suspected of SAS underwent
      full polysomnography recordings concomitantly with the use of the SleepStrip. For
      all samples combined, the correlation between AHI and Sscore was r=0.73,
      sensitivity and specificity values ranged from 80-86% and 57-86% respectively,
      and the area under the curve derived from receiver-operating characteristic
      curves ranged from 0.81-0.92 at varying AHI thresholds. Though not intended as a
      substitute for polysomnography, the SleepStrip may provide initial screening
      information, which may be useful in both clinical and experimental settings.

PMID- 11843311
TI  - Lung cancer risk in a population-based cohort of patients hospitalized for asthma
      in Sweden.
AB  - It has been suggested that asthma increases the risk of lung cancer in males but
      not in females. However, previous studies may suffer from report bias and are
      based on a small numbers of cases. The objective of the present study was to
      assess the incidence of lung cancer in males and females using a nationwide
      Swedish cohort of asthma patients. Patients (n=92,986) aged > or = 20 yrs with a
      hospital-discharge diagnosis of asthma and who were alive and free from
      malignancy I yr after first hospitalization were followed-up, for incidence of
      lung cancer during the period 1965-1994 (average duration of follow-up, 8.5 yrs).
      Their incidence of lung cancer was compared with that of the national population.
      The authors observed 713 lung cancers (standardized incidence ratio (SIR) 1.58,
      95% confidence interval (CI) 1.47-1.70). The SIR was 1.51 in males (95% CI 1.38
      1.65, 492 cases) and 1.78 in females (95% CI 1.55-2.03, 221 cases). The SIR
      decreased with duration of follow-up and increased with calendar period and age
      at first hospitalization. The risk of lung cancer was higher for squamous cell
      and small cell carcinoma than for adenocarcinoma, and it was higher in patients
      with other diseases as the main diagnosis and in patients hospitalized in
      departments other than internal and respiratory medicine. It was confirmed that
      asthma patients are at increased risk of lung cancer, but there is no
      heterogeneity in risk between the sexes. Several indirect arguments point towards
      a noncausal explanation of these findings; in particular, confounding by tobacco
      smoking is a plausible explanation.

PMID- 11843312
TI  - BAX and p16INK4A are independent positive prognostic markers for advanced tumour
      stage of nonsmall cell lung cancer.
AB  - Clinical studies suggest prognostic relevance of p16INK4A in nonsmall cell lung
      cancer (NSCLC) while conflicting results for p53 have been published. However,
      the importance of the apoptosis regulating gene BAX, a downstream regulator of
      p53, on the prognosis of NSCLC is unknown. The present study investigated the
      prognostic relevance of BAX with respect to the status of p53 and P16INK4A in 61
      patients with advanced NSCLC. Protein expression of BAX, p53 and p16INK4A was
      investigated retrospectively by immunohistochemistry. Tumour deoxyribonucleic
      acid (DNA) was screened for p53 mutations by single strand-conformation
      polymorphism polymerase chain reaction (PCR) and BAX frameshift mutations by
      fragment length analysis. Patients with positive BAX protein expression had a
      significantly longer median survival (14 months) than those patients without BAX
      expression (6 months, p=0.0004). In contrast, p53 status did not influence
      prognosis. Patients with p161NK4A negative tumours had a significantly shorter
      survival (4 months) than those with p16INK41 protein expression (15 months,
      p=0.0001). Furthermore, the loss of p16INK4A protein expression correlated
      strongly with the pressure of distant and advanced lymph-node metastases. The
      best survival was seen in a subgroup of 20 patients with positive p16INK4A
      expression and intact BAX (p=0.0002). The results of the present study suggest
      that the loss of BAX and p16INK4A expression are independent markers for poor
      prognosis in nonsmall cell lung cancer. The study suggests that multimarker
      analysis of genes involved in apoptosis may be useful for determining individual
      therapy and for identifying targets for gene-replacement therapy. This should be
      assessed in a prospective study with a larger cohort of patients.

PMID- 11843313
TI  - A portable forced oscillation device for respiratory home monitoring.
AB  - The increase in the prevalence of chronic respiratory diseases has resulted in a
      rise in health services provided at home. The forced oscillation technique (FOT)
      proves to be a useful tool when it is desired to assess lung function
      noninvasively, and particularly for patients in whom spirometry cannot be
      applied. As no portable FOT device is currently available, the aim of this study
      was to design and test a portable FOT system for ambulatory and home care
      applications. The system devised is based on a microprocessor, which allows
      online computation of respiratory resistance (Rrs) and reactance (Xrs) and
      reliability indices. The portable device was compared with a conventional FOT
      system by using signals from 14 patients with chronic respiratory disease. This
      device has the same computation capabilities and flexibility as conventional FOT
      systems and meets the requirements for home application. Rrs (14.2 +/- 6.0 cmH2O
      x s x L(-1), mean +/- SD) and Xrs (-5.3 +/- 2.7 cmH2O x s x L(-1)) measured at 5
      Hz by the portable system virtually coincided with those computed with the
      reference conventional FOT system: mean differences +/-SD were 0.074 +/- 0.025
      and 0.005 +/- 0.009 cmH2O x s x L(-1), respectively. This portable forced
      oscillation technique device could be a useful tool for monitoring respiratory
      mechanics in ambulatory and home care applications.

PMID- 11843314
TI  - Allergy and immunity to fungal infections and colonization.
AB  - Innate and cell-mediated immunity are considered as the principal defence lines
      against fungal infections in humans. Most opportunistic mycoses occur in
      individuals with defective innate and/or adaptive cellular immunity. The
      morbidity and mortality rates associated with infections caused by fungal
      pathogens are high, and prevention, diagnosis and treatment of these infections
      remain quite difficult. A variety of pathological conditions, including impaired
      immune function, are believed to cause host susceptibility to fungal infections
      as well as to determine the severity and characteristics of the associated
      pathology. Nonspecific cellular immunity, mediated by macrophages, neutrophils
      and natural killer cells, provides efficient protection against fungal infections
      in healthy individuals. A major reason for the increase in systemic mycoses is
      undoubtedly related to an increased number of patients with congenital or
      acquired immunodeficiencies. However, there is increasing clinical and
      experimental evidence indicating that antigen-specific cellular immunity may also
      play a critical role in host protection against fungi. A better understanding of
      reciprocal regulation between innate, humoral and adaptive immune responses in
      the development of an optimal antifungal immunity and, in particular, the
      improved definition of fungal antigens, may lead to a clarification of the
      mechanisms involved in host immunity to fungal infections. Molecular cloning and
      characterization of fungal antigens reveals the involvement of related cross
      reactive molecular structures produced by different fungi as pathological
      molecules involved in development of allergic reactions.

PMID- 11843315
TI  - The bidirectional capacity of bacterial antigens to modulate allergy and asthma.
AB  - In recent decades, the prevalence of allergic diseases including bronchial
      asthma, hay fever and atopic dermatitis, has risen steadily in high-income
      countries. The underlying mechanisms for this phenomenon remain largely unknown.
      Since the natural mutation rate is low, altered environmental and lifestyle
      conditions are thought to play an important role. Epidemiological and clinical
      studies have provided indirect evidence that infections may prevent the
      development of atopy and atopic disease. This is referred to as the "hygiene
      hypothesis". According to the hygiene hypothesis, viral and/or bacterial
      infections could inhibit the T-helper (Th)-2 immune response associated with
      atopic reactions by stimulating a Th-1 response involved in defence of bacterial
      infections and delayed-type hypersensitivity reactions. In particular, the
      prenatal period and early childhood are considered to be critical for the
      establishment and maintenance of a normal Th-1/Th-2 balance. On the other hand,
      several studies suggested that infections exacerbate established allergic
      diseases, e.g. bronchial asthma, airway hyperresponsiveness and atopic
      dermatitis. Therefore, viral and/or microbial infections and/or their products
      may have bidirectional effects on the development of allergy and asthma. This
      review will focus on recent findings related to the interaction between allergic
      disorders and infectious diseases, with the main emphasis on bacterial
      infections.

PMID- 11843316
TI  - Nasal peak inspiratory flow at altitude.
AB  - The present study investigated whether there are changes in nasal peak
      inspiratory flow (NPIF) during hypobaric hypoxia under controlled environmental
      conditions. During operation Everest III (COMEX '97), eight subjects ascended to
      a simulated altitude of 8,848 m in a hypobaric chamber. NPIF was recorded at
      simulated altitudes of 0 m, 5,000 m and 8,000 m. Oral peak inspiratory and
      expiratory flow (OPIF, OPEF) were also measured. Ambient air temperature and
      humidity were controlled. NPIF increased by a mean +/- SD of 16 +/- 12% from sea
      level to 8,000 m, whereas OPIF increased by 47 +/- 14%. NPIF rose by 0.085 +/-
      0.03 L x s(-1) per kilometre of ascent (p<0.05), significantly less than the rise
      in OPIF and OPEF of 0.35 +/- 0.10 and 0.33 +/- 0.04 L x s(-1) per kilometre
      (p<0.0005). Nasal peak inspiratory flow rises with ascent to altitude. The rise
      in nasal peak inspiratory flow with altitude was far less than oral peak
      inspiratory flow and less than the predicted rise according to changes in air
      density. This suggests flow limitation at the nose, and occurs under controlled
      environmental conditions, refuting the hypothesis that nasal blockage at altitude
      is due to the inhalation of cold, dry air. Further work is needed to determine if
      nasal blockage limits activity at altitude.

PMID- 11843318
TI  - Detection of Chlamydia pneumoniae in unexplained pulmonary hypertension.
AB  - The pathogenesis of primary pulmonary hypertension is still unclear. The case of
      a 68-yr-old female patient who complained of recurrent dizzy spells and collapses
      over a period of 6 weeks and died of global cardiac failure is presented. Autopsy
      revealed severe pulmonary hypertension, slight chronic bronchitis, and
      bronchiolitis as well as intra-alveolar accumulation of macrophages. Chlamydiae
      were detected within the pulmonary arteries and in intramural and intra-alveolar
      macrophages by immunofluorescence, confocal laser scanning microscopy, scanning
      and transmission electron microscopy. Nested-polymerase chain reaction (PCR) and
      nonradioactive deoxyribonucleic acid (DNA) hybridization of PCR products from
      pulmonary arteries revealed Chlamydia pneumoniae DNA. Chlamydia pneumoniae has
      already been detected in atherosclerosis and in pulmonary emphysema. It can
      induce proliferation of smooth muscle cells. Chlamydia pneumoniae might be
      relevant in aggravation of primary pulmonary hypertension and might perhaps be a
      trigger factor in some cases.

PMID- 11843317
TI  - Scientific rationale for inhaled combination therapy with long-acting beta2
      agonists and corticosteroids.
AB  - The addition of an inhaled long-acting beta2-agonist (LABA) to an inhaled
      corticosteroid (ICS) gives optimal control of asthma in most patients and two
      fixed combination inhalers (salmeterol/fluticasone and formoterol/budesonide) are
      increasingly used as a convenient controller in patients with persistent asthma.
      There is a strong scientific rationale for the combination of these two drug
      classes. ICS suppress the chronic inflammation of asthma and reduce airway
      hyperresponsiveness and this is achieved at low doses in most patients. LABA act
      on different aspects of the pathophysiology of asthma. In addition to their
      bronchodilator action, LABA also inhibit mast cell mediator release, plasma
      exudation and may reduce sensory nerve activation. Thus these two classes of drug
      address complementary aspects of the pathophysiology of asthma that neither drug
      class is able to achieve alone. There are several positive interactions between
      LABA and ICS. Corticosteroids increase the expression of beta2-receptors by
      increasing gene transcription. Experimentally this protects against the loss of
      beta2-receptors in response to long-term exposure to beta2-agonists. While this
      is unlikely to be important in bronchodilator responses to beta2-agonists, in
      view of the large beta-receptor reserve, it is probably important in preventing
      loss of beta-agonist effects on the nonbronchodilator actions of LABA discussed
      earlier. beta2-Agonists may potentiate the molecular mechanism of corticosteroid
      actions, with increased nuclear localization of glucocorticoid receptors and
      additive or sometimes synergistic suppression of inflammatory mediator release.
      Thus LABA and ICS may optimize each others beneficial actions in the airways, but
      the low systemic effects of these drugs do not result in any increase in adverse
      effects. Long-acting beta2-agonists corticosteroid inhaler therapy is therefore a
      logical advance and results in effective control of asthma in the majority of
      patients without significant adverse effects. This simplified approach to long
      term asthma therapy has a strong scientific rationale.

PMID- 11843319
TI  - Ehlers-Danlos syndrome type IV with few extrathoracic findings: a newly
      recognized point mutation in the COL3A1 gene.
AB  - Ehlers-Danlos syndrome type IV (EDS IV) is caused by mutation within the COL3AI
      gene, resulting in the disorder of type III procollagen. The diagnosis is
      confirmed by demonstrating the synthesis of abnormal type III procollagen
      molecules from cultured dermal fibroblasts or by identifying the mutation in the
      COL3A1 gene. The authors report a case of EDS IV caused by a novel point mutation
      in the COL3A1 gene in a 16-yr-old female. Recurrent haemoptysis and cavitary
      formation of the lung were evidence of pulmonary involvement. However,
      extrathoracic manifestations of EDS IV were mostly absent. To the best of the
      authors' knowledge, all previously reported Ehlers-Danlos syndrome IV patients
      with respiratory disease had the characteristic findings or histories of Ehlers
      Danlos syndrome IV. In the present case, connective tissue friability was
      suspected due to tissue laceration observed in the biopsied lung specimen, and
      the diagnosis was made beginning from this pivotal finding.

PMID- 11843320
TI  - Recurrent pneumonia after cardiac surgery.

PMID- 11843321
TI  - Obliterative bronchiolitis: varying presentations and clinicopathological
      correlation.
AB  - In obliterative bronchiolitis, inflammation and fibrosis lead to narrowing or
      occlusion of bronchiolar lumina. To determine how bronchiolar structural
      alterations relate to lung physiology, 19 patients with a pathological diagnosis
      of obliterative bronchiolitis were studied. The bronchiolar inflammatory and
      fibrotic features were correlated to the clinical presentation, and lung function
      tests. Eleven patients demonstrated airflow limitation, one had a restrictive
      pattern and one had a mixed pattern, two had isolated gas trapping, but four had
      normal spirometry. Mild-to-moderate bronchiolar inflammation was invariably
      present. It involved 60% of bronchioles subepithelially and 54% in the
      adventitia. Subepithelial fibrosis was observed in 15 patients and adventitial in
      12. Adventitial bronchiolar inflammation correlated with forced expiratory volume
      in one second and forced vital capacity and inversely correlated with residual
      volume. Subepithelial fibrosis inversely correlated with subepithelial and
      adventitial inflammation. High-resolution computed tomography in 10 patients
      revealed inspiratory (five out of 10) and expiratory air trapping (five out of
      five), ground glass opacities (seven out of 10), bronchial wall thickening (five
      out of 10), bronchiectasis (two out of 10) and centrilobular nodules (two out of
      10). The present study suggests that inflammation and fibrosis occurs in
      bronchioles at different time points in the disease process, or that there is no
      transition between these types of pathology in the same patient. No correlation
      was observed between the degree of bronchiolar fibrosis and the degree of airflow
      limitation.

PMID- 11843322
TI  - Prevalence of nasal symptoms and their relation to self-reported asthma and
      chronic bronchitis/emphysema.

PMID- 11843323
TI  - Early diagnosis of bronchial stent related malignant respiratory fistulas.

PMID- 11843324
TI  - Pertechnegas lung clearance in different forms of interstitial lung disease.
AB  - Interstitial lung diseases (ILD) are characterized by an acute or chronic
      inflammation of the alveolar capillary membrane, which affects the permeability
      of this membrane. A possible way to measure the permeability of the membrane is
      by radionuclide aerosol imaging. Pertechnegas, a gas composed of technetium
      labelled carbon particles, has recently been proposed as a new ventilation agent
      to measure this lung clearance. The clearance by pertechnegas in the four most
      common forms of ILD (eight patients with connective tissue disease, 10 with
      hypersensitivity pneumonitis, nine with idiopathic interstitial pneumonia and 10
      with sarcoidosis) was measured and compared with 10 nonactive smoking controls.
      Because forced vital capacity (FVC), total lung capacity (TLC) and carbon
      monoxide diffusing capacity of the lung (DL,CO) are used in the assessment of
      functional severity of the ILD, the pertechnegas clearance was correlated with
      these lung-function indices. It was found that the time to half clearance of
      pertechnegas of the lung is significantly decreased in idiopathic interstitial
      pneumonia (p<0.0001), hypersensitivity pneumonitis (p=0.0005) and connective
      tissue disease (p=0.002) but not in sarcoidosis when compared with 10 nonsmoking
      controls. A significant correlation is also found between time to half clearance
      and FVC (r=0.76; p<0.0001), TLC (r=0.63; p<0.0001) and DL,CO (r=0.75; p<0.0001)
      for all groups together. For all subjects as a group, the time to half clearance
      is shorter in the upper lung zones than in the lower zones (p<0.0001) and the
      ratio between both zones is not significantly different between the different
      types of disease. These results indicate that pertechnegas clearance is increased
      in idiopathic interstitial pneumonia, hypersensitivity pneumonitis and connective
      tissue disease, but not in sarcoidosis and is related to the functional severity
      of the disease.

PMID- 11843325
TI  - Relationship of carbon dioxide tension in arterial blood to pulmonary wedge
      pressure in heart failure.
AB  - Hypocapnia contributes to the genesis of Cheyne-Stokes respiration and central
      sleep apnoea in patients with congestive heart failure (CHF) and is associated
      with increased mortality. However, the cause of hypocapnia in patients with
      chronic stable CHF is unknown. Since pulmonary congestion can induce
      hyperventilation via stimulation of pulmonary vagal afferents, the present study
      tested the hypothesis that in patients with CHF (carbon dioxide tension in
      arterial blood (Pa,CO2)) is inversely related to pulmonary capillary wedge
      pressure (PCWP), and that alterations in PCWP would cause inverse changes in
      Pa,CO2. In 11 CHF patients undergoing diagnostic cardiac catheterization,
      haemodynamic variables and arterial blood gas tensions were measured
      simultaneously at baseline. In three patients, these measurements were repeated
      after coronary angiographic dye infusion and nitroglycerine infusion. At
      baseline, Pa,CO2 correlated inversely with PCWP (r=-0.80, p=0.003). In the three
      patients in whom multiple measurements were made, acute alterations in PCWP
      caused inversely proportional changes in Pa,CO2. The present study concludes that
      in patients with congestive heart failure, pulmonary capillary wedge pressure is
      an important determinant of carbon dioxide tension in arterial blood. These
      findings imply that hypocapnia in patients with chronic stable congestive heart
      failure is a respiratory manifestation of elevated left ventricular filling
      pressures.

PMID- 11843326
TI  - Nasal airflow resistance at simulated altitude.

PMID- 11843327
TI  - Improved quality of life after lung volume reduction surgery.
AB  - Lung volume reduction surgery (LVRS) improves dyspnoea, pulmonary function, and
      physical performance in patients with severe pulmonary emphysema. This study
      investigated the impact of LVRS on health-related quality of life (HRQL) over a 2
      yr period following surgery. Thirty-nine consecutive patients were prospectively
      assessed before LVRS, and followed over 24 months postoperatively. The
      assessments included pulmonary function, dyspnoea (Medical Research Council (MRC)
      dyspnoea score), 6-min walking distance (6MWD) and HRQL using the Short Form 36
      item questionnaire (SF-36). Several domains of SF-36 improved considerably over 2
      yrs after surgery: Physical Functioning: 39 +/- 4 (mean +/- SEM) versus 16 +/- 2
      (p<0.01); Vitality: 51 +/- 3 versus 32 +/- 3 (p<0.01); Social Functioning: 72 +/-
      4 versus 51 +/- 5 (p<0.01). Also, improvements in pulmonary function (forced
      expiratory volume in one second (FEV1): 27 +/- 1% predicted, residual volume
      (RV)/total lung capacity (TLC): 0.65 +/- 0.01), 6 MWD (274 +/- 16 m) and dyspnoea
      (MRC: 3.9 +/- 01) were sustained for up to 2 yrs after LVRS (FEV1 36 +/- 2% pred,
      RV/TLC: 0.58 +/- 0.02; 6 MWD: 342 +/- 19 m; MRC: 2.0 +/- 0.2; p<0.05). In
      patients with severe emphysema, lung volume reduction surgery had positive
      effects on health-related quality of life and pulmonary function over 2 yrs.

PMID- 11843328
TI  - Understanding cough.

PMID- 11843329
TI  - Costs of asthma are correlated with severity: a 1-yr prospective study.
AB  - Asthma prevalence is increasing and asthma-related costs are likely to increase,
      but few studies have analysed the relationship of asthma costs and severity. The
      impact of severity on costs was quantified in a cohort of 318 asthmatic patients
      followed up prospectively for 1 yr. Patients presenting with a broad range of
      severity of the disease (intermittent, mild persistent, moderate persistent,
      severe persistent) were recruited by chest physicians throughout France and
      treated for 1 yr according to customary clinical practice and following
      international guidelines. Severity, direct and indirect costs, and quality of
      life (QoL) were assessed. A multivariate analysis was conducted to relate factors
      contributing to the costs measured. Mean direct costs for goods and services
      excluding hospitalization, numbers of consultations, supplementary examinations,
      and the use and cost of bronchodilators and corticosteroids, indirect costs of
      days lost from work, and adverse QoL parameters all increased significantly with
      increasing severity. This also applied to mean age, body weight, asthma duration,
      depression of forced expiratory volume in one second, and inhaled corticosteroid
      posology in the 234 patients completing the study. There was a significant
      relationship (r=0.614, p<0.001) between direct costs (hospitalization and cures
      were excluded) and three domains of the QoL questionnaire (mobility, pain and
      energy). Overall costs of asthma (including individual direct costs, indirect
      costs, and intangible quality of life costs) are clearly related to severity.
      This is the first study in asthma to combine rigorous independent classification
      of grades of severity in statistically valid numbers of patients of grades
      receiving "real-world" treatment and followed-up prospectively for 1 yr. It
      allowed severity to be accurately related to direct, indirect and intangible
      costs of asthma. Quality of life explained a significant part of these costs.

PMID- 11843330
TI  - Dissociation between airway responsiveness to methacholine and responsiveness to
      antigen.
AB  - Repeated aerosolized antigen challenges to brown Norway (BN) rats generate
      nonspecific airway hyperresponsiveness (AHR). On the other hand, some studies
      have demonstrated that repeated antigen challenge could attenuate antigen
      specific AHR in BN rats. The authors questioned whether such dissociation in
      airway responses actually occurs when assessed in a single study in the same
      animals. The authors simultaneously measured AHR to methacholine and antigen
      specific AHR in rats that were repeatedly exposed to aerosolized ovalbumin (OA)
      for 1 or 3 months after sensitization. Four days after the last challenge, airway
      responses to methacholine and OA, morphometry of the airways, the cell profile in
      bronchoalveolar lavage fluid, and cytokine messenger ribonucleic acid (mRNA)
      expression in the lungs were evaluated. The two types of AHR were modulated in
      opposite directions by repeated antigen challenges. The AHR to methacholine was
      significantly increased in the rats receiving antigen challenges compared with
      the control rats receiving saline challenges after sensitization; whereas, the
      antigen-specific AHR was significantly decreased. The number of alveolar
      macrophages in lavaged fluid and the expression of transforming growth factor
      beta1 mRNA in lung tissue was significantly different between the antigen
      challenged rats and the control rats. In conclusion, dissociation between
      nonspecific airway hyperresponsiveness and antigen-specific airway
      hyperresponsiveness in brown Norway rats after repeated antigen challenges was
      demonstrated. Sustained airway inflammation with macrophages and/or upregulation
      of transforming growth factor-beta1 messenger ribonucleic acid in the lung tissue
      may be responsible for this dissociation.

PMID- 11843331
TI  - Physical exercise, sports, and lung function in smoking versus nonsmoking
      adolescents.
AB  - Associations between adolescent smoking habits and exercise, particularly
      participation in sports and lung function were studied. All students aged 13-19
      yrs in Nord-Trondelag County, Norway, 1995-1997, were invited to join a cross
      sectional study. Information on smoking habits and exercise was obtained by self
      administered questionnaire. Spirometry was performed in accordance with American
      Thoracic Society standards. Of the 6,811 students (aged 13-18 yrs, without
      asthma), 2,993 (44%) reported never-smoking, and 1,342 (20%) reported current
      smoking (90% daily). Frequency of physical exercise was inversely associated with
      smoking, but participants in individual sports with lesser endurance, especially
      body-building and fighting sports, were more likely to be daily smokers than
      nonparticipants. Both daily (53%) and occasional smokers (43%) were more likely
      to have quit sports than never-smokers (26%)). Never-smokers showed a positive
      dose-response between physical exercise and lung function (forced vital capacity
      and forced expiratory volume in one second, adjusted for age and height). No
      similar significant association was observed in daily smokers. These data suggest
      that smoking habits in different sports should be considered when promoting
      physical activity as smoking prevention, and sports organizations should include
      smoking prevention programmes. Adolescents with better lung function may self
      select into sports; this possibility needs to be studied in a longitudinal
      design.

PMID- 11843332
TI  - Occupational asthma in France: a 1-yr report of the observatoire National de
      Asthmes Professionnels project.
AB  - Observatoire National des Asthmes Professionnels (ONAP) was created in 1996 by
      two French professional societies to estimate the incidence of occupational
      asthma and to promote preventive measures against it. Occupational and chest
      physicians were asked to report newly diagnosed cases of work-related asthma and
      reactive airway dysfunction syndrome (RADS), the information collected included
      age, sex, occupation, suspected causal agents and diagnostic methods. In 1997,
      82.3% of 559 cases reported (64% males, mean age 36 +/- 13 yrs) involved
      occupational asthma, 4.7% RADS and 12.7% atypical asthma syndromes. Incidence
      rates (expressed as number of cases per million workers) showed a regional
      variation that ranged from 4 to 73 (national mean: 25.7). The most frequently
      suspected agents were flour (23.3%), followed by isocyanates (16.6%), latex
      (7.5%), aldehydes (5.5%), and persulphates (4.1%). Occupations at risk were
      bakers (23.9%), healthcare workers (12%), painters (9.1%), hairdressers (5.2%),
      wood industry workers (4.8%) and cleaners (3.5%). These results are compared to
      those of other systems set up in Europe and North America. Because of the
      considerable bias inherent in a surveillance system based on voluntary,
      reporting, the number of occupational asthma cases reported is probably lower
      than the real incidence. Nevertheless, the French National Observatory for
      Occupational Asthma encourages physician awareness of occupational asthma and
      provides an estimate of its incidence and aetiologies in France.

PMID- 11843333
TI  - Excess incidence of asthma among Finnish cleaners employed in different
      industries.
AB  - The incidence and risk of asthma among female cleaners employed in different
      industries was explored. An increased risk of asthma has been associated with the
      cleaning profession, in some but not all studies. All Finnish females employed as
      cleaners and all those employed in administrative work were followed for asthma
      incidence through a record linkage in 1986-1998. An individual was defined as an
      "incident case of asthma" if they received rights for special reimbursement of
      asthma medication from the national health insurance or were recognized as having
      occupational asthma. Age-adjusted relative risks (RR) were estimated for cleaners
      in comparison with those employed in administrative work. There were 2,414 and
      5,235 cases of asthma among the cleaners and administrative workers,
      respectively. The RR was 1.50 (95% confidence interval (CI) 1.43-1.57) in
      cleaners. The risk was increased in cleaners working in nearly all major sectors
      of economic activity, but cleaners employed by companies concerned with the
      manufacture of basic metals (RR 2.47; 95% CI 1.68-3.64) and food products (RR
      2.19; 95% CI 1.69-2.85) had the highest risk. Only 25 of the "cases of asthma"
      among cleaners had been recognized as being occupational asthma. It could be
      concluded that cleaners have an increased risk of persistent adult-onset asthma.
      Factors inherent to the environment where cleaning is performed or differences in
      the cleaning agents used may explain the observed differences between industries.

PMID- 11843334
TI  - Host determinants for the development of allergy in apprentices exposed to
      laboratory animals.
AB  - The aim of this study was to evaluate whether determinants of work-related
      symptoms, skin sensitization and diseases differ between atopic and nonatopic
      subjects starting a career with exposure to laboratory animals (LA). A cohort of
      417 apprentices in animal-health technology was prospectively followed during 32
      or 44 months. The effect on the study outcomes of variables derived from
      questionnaire, skin reactivity, and lung function assessments at baseline were
      compared in atopic (n=212) and nonatopic (n=183) subjects. Eighty-five incident
      cases of sensitization to a LA-derived allergen were identified, 67 among atopic
      and 18 among nonatopic subjects. Baseline rhinitis symptoms in contact with pets
      and skin sensitization to pets were associated with the development of work
      related rhinoconjunctivitis (RC) symptoms in atopic subjects, whereas perannual
      rhinitis symptoms and having a PC20 (provocative concentration causing a 20% fall
      in forced expiratory volume in one second) < or = 32 mg x mL(-1) were associated
      in nonatopic subjects. Baseline rhinitis symptoms on contact with pets and a PC20
      value < or = 32 mg x mL(-1) were significant determinants for developing
      sensitization to a specific allergen in atopic subjects only. Finally, baseline
      rhinitis symptoms in contact with pets and perannual rhinitis symptoms were
      associated with the development of occupational RC in atopic subjects, whereas in
      nonatopic subjects this was associated with having a PC20 value < or = 32 mg x
      mL(-1). In conclusion, the determinants for the development of specific skin
      sensitization, symptoms and disease are different between atopic and nonatopic
      apprentices starting occupational exposure to laboratory-animal-derived
      allergens.

PMID- 11843335
TI  - On the proper use of quantities and units.

PMID- 11843336
TI  - Differential dosimetry in a neutron-proton mixed field with low-pressure
      proportional counters.
AB  - For a mixed radiation field of neutrons and protons, radiation events were
      discriminated between photons, neutrons, and protons using a thin plastic
      scintillator. Distributions of lineal energy were measured with low-pressure
      proportional counters (LPPCs). To estimate the distribution of lineal energy for
      ICRU muscle, measurements were carried out using A-150-walled, graphite-walled,
      ZrO2-walled, and Zr-walled counters. Data were corrected for different atomic
      compositions between the A-150 plastic and ICRU muscle.

PMID- 11843337
TI  - A Monte Carlo investigation of electron backscattering.
AB  - Kearsley's, Haider's and Frujinoiu's cavity expressions depend upon the existence
      of reliable data on electron backscattering in different media. These data are
      not available in the literature. By using MCNP, backscatter distributions and
      their saturation values were obtained for electron beams with energies between
      0.1 MeV and 9 MeV traversing different materials such as polyethylene, solid
      water, lithium fluoride, aluminium, copper and lead. The data obtained using MCNP
      show that electron backscatter probability most strongly depends on the
      scatterer's effective atomic number and electron energy. Backscatter probability
      becomes less dependent on energy and is mostly a function of the effective atomic
      number of the scatterer for electron energies below 0.5 MeV. For low atomic
      number materials MCNP data suggest that the backscatter saturation values are
      distributed linearly with the effective atomic number of the scatterer for all
      energies investigated.

PMID- 11843338
TI  - Long-term retention of injected barium-133 in man.
AB  - Data are presented on the whole-body retention of 133Ba (half-life 10.74 y), over
      periods of up to 13 y after injection into six healthy male volunteers aged 25
      81, and on their levels of biochemical markers for bone turnover. The results are
      relevant to propositions underlying the ICRP's current (Publication 67) and
      former (Publication 20) models of alkaline earth metabolism. The tracer was
      predominantly skeletal within weeks of the injection, as predicted in the current
      model. The mean retention accorded satisfactorily throughout with predictions
      based on the current model, but this accord does not necessarily validate the
      model, for two reasons. First, parameter values attributed to barium were
      influenced by data emerging during the early years of this study. Second, bone
      resorption rates in these subjects, as indicated by urinary markers, appear
      insufficient to explain the long-term reductions in skeletal retention which, in
      the present model, arise exclusively through this mechanism.

PMID- 11843339
TI  - Human absorption and retention of polonium-210 from caribou meat.
AB  - The gastrointestinal (GI) absorption factors and the biological retention times
      for polonium were determined for a group of 14 volunteers--seven men and seven
      women--from Saskatoon, Saskatchewan, Canada. Each volunteer consumed 2.0 kg of
      caribou meat containing known amounts of naturally occurring 210Po. Urine and
      faecal samples were collected for up to 65 days after meat consumption and
      analysed for 210Po. The average GI absorption factor for the 14 volunteers was 56
      +/- 4% (range = 31-71%), not significantly different from the ICRP value of 50%.
      About 3% of absorbed polonium underwent prompt excretion by the urinary pathway.
      The remainder was retained by the body with a half-time >100 days, compared to
      the ICRP value of 50 days. The effect of these findings increases the dose
      estimate for ingestion of 210Po in food by a factor of 1.5 to 3.5. Thus,
      background doses to people consuming caribou and reindeer may be higher than
      previously thought.

PMID- 11843340
TI  - Personal radon dosimetry from eyeglass lenses.
AB  - Eyeglass lenses are commonly composed of allyl-diglycol carbonate (CR-39), an
      alpha-particle detecting plastic, thus making such lenses personal radon
      dosemeters. Samples of such lenses have been obtained, etched to reveal that
      radon and radon progeny alpha tracks can be seen in abundance, and sensitivities
      have been calibrated in radon chambers as a primary calibration, and with a
      uranium-based source of alpha particles as a convenient secondary standard. With
      one exception natural, environmental (fossil) track densities ranged from less
      than 3,000 to nearly 70,000 per cm2 for eyeglasses that had been worn for various
      times from one to nearly five years. Average radon concentrations to which those
      wearers were exposed are inferred to be in the range 14 to 130 Bq x m(-3) (0.4 to
      3.5 pCi x l(-1)). A protocol for consistent, meaningful readout is derived and
      used. In the exceptional case the fossil track density was 1,780,000 cm(-2) and
      the inferred (24 h) average radon concentration was 6500 Bq x m(-3) (175 pCi x l(
      1)) for a worker at an inactive uranium mine that is used for therapy.

PMID- 11843341
TI  - Radon exposures from the use of natural gas in buildings.
AB  - Low levels of natural radioactivity in the ground produce radon-222 and its decay
      products which can be entrained with gas streams and become distributed with gas
      supplies to commercial and domestic users. Levels of radon in blended gas
      received by most users are comparable with the levels that are present naturally
      in buildings as a result of ingress from the ground and this is further diluted
      during the combustion process. For typical rates of gas usage with an average
      radon level of about 200 Bq x m(-3), the estimated dose from the use of natural
      gas is estimated at 4 microSv, less than 1% of the dose from radon exposure at
      the average level in UK homes. Commercial users may receive somewhat higher
      doses, and the estimate for a critical group is a few tens of microsievert. The
      total radon emission to the environment is estimated at about 10(13) Bq x y(-1)
      which represents less than 10(-4) of the natural emission rate from the ground.
      There is some variability of radon levels in gas from different sources and it
      would be prudent to keep this source of exposure under review. A standard
      sampling and measurement protocol has been developed in conjunction with a
      technical group representing the industry.

PMID- 11843342
TI  - Radon exposure in Slovenian spas.
AB  - Radon and gamma dose rates were surveyed in five Slovenian spas, at Rogaska
      Slatina, Radenci, Moravci, Podcetrtek, and Catez. Due to effective ventilation
      systems, the indoor air radon concentration rarely exceeds 200 Bq x m(-3) and is
      usually lower. Uncer the present operationsal conditions and working regimes of
      the spas, there is no basis for concern about elevated exposure of personnel to
      radon.

PMID- 11843343
TI  - 241Am as a metabolic tracer for inhaled plutonium nitrate in external chest
      counting.
AB  - The plutonium (Pu) treated in the nuclear fuel cycle is usually accompanied by
      241Am produced from 241Pu by beta disintegration, which emits gamma rays of 60
      keV with the emission rate of 0.36, being more penetrating than the L X rays from
      Pu. The 241Am could imprve the detection limit of chest counting of Pu, if it was
      being used as a metabolic tracer for Pu in lungs. Young adult male Wistar rats
      were exposed to polydisperse aerosols of Pu(NO3)4 with 0.6 microm in activity
      median aerodynamic diameter. They were periodically killed and the radioactivity
      of 241Am was cleared from the lungs at almost the same rate as the Pu at least
      for half a year post-inhalation, which proved the validity of 241Am as a
      metabolic tracer for inhaled Pu nitrate in external chest counting.

PMID- 11843344
TI  - Patient dose variation investigated in four Irish hospitals for barium meal and
      barium enema examinations.
AB  - Four hospitals have been studied, intra- and inter-hospital variations examined
      and the mean DAP values recorded for barium enemas and barium meals. Mean DAP
      values for barium meals and barium enemas at 11.4 Gy x cm2 and 20.1 Gy x cm2
      respectively have been shown. Differences between individual examinations for
      barium meals varied by up to a factor of 185 and for barium enemas, up to a
      factor of 19, with hospital means for barium meal and enema examinations each
      differing by up to a factor of 3. The data provided by this study have suggested
      that large variations in patient dose do exist in Ireland for barium meal and
      barium enema examinations. Fluoroscopy time was shown to be a major contributor
      to the variations reported, with number of images playing a minor role. Results
      have demonstrated the need for standardisation of technique throughout the
      country for these examinations.

PMID- 11843345
TI  - Is the linear-no-threshold hypothesis appropriate for use in radiation
      protection? Favouring the proposition.

PMID- 11843346
TI  - Is the linear-no-threshold hypothesis appropriate for use in radiation
      protection? Opposing the proposition.

PMID- 11843347
TI  - The magnitude of the unit of gray.

PMID- 11843348
TI  - Current research activity in the measurement of thorium and the identification of
      future research needs.
AB  - A pre-requisite in the setting and enforcement of regulatory limits for exposure
      to thorium in the workplace is that thorium and its progeny can be accurately
      measured. Literature surveys have shown that the majority of thorium measurements
      were performed using either a radiochemical technique, such as alpha or gamma
      spectroscopy, or ICP-MS. For many methods. there was a separation step to isolate
      and pre-concentrate thorium from the sample matrix. Thorium was most commonly
      measured in geological matrices and industrial materials. A survey of current
      research activity was performed through distribution of a questionnaire to
      laboratories and national centres. From the rcsponses, four areas of current
      activity were identified: (i) development of methods for low level thorium
      determination, (ii) biological monitoring and metabolism of thorium, (iii)
      environmental monitoring for thorium, and (iv) health risks from X ray contract
      media. Two key areas for priority research were identified by the thorium
      Thematic Network: namely sample preparation methods and for traceable standards
      and reference materials for thorium analysis.

PMID- 11843349
TI  - Experiences in the determination of activity in thorium contaminated materials in
      working areas, using gamma spectrometer measurements, from the viewpoint of
      practical radiation protection.
AB  - In industrial processes, classification and clearance of thorium contaminated
      material is often a time problem. Short-term decisions have to be made about
      acceptance limits, industrial safety as the workers are in contact with the
      contaminated material. and the environmental aspect regarding the disposal of the
      wastes. The use of gamma ray spectrometry measurements is an easy method to
      estimate the level of activity in materials. Under the precondition of
      equilibrium of activity within the thorium decay chain, which can be assumed only
      with knowledge of the materials' history, adequate results can be produced in a
      reasonable time. The advantages of gamma ray spectrometry are the low investment
      and operational costs, simple sample preparation, and a system that is relatively
      quick and easy to operate.

PMID- 11843350
TI  - Thorium isotopic analysis by alpha spectrometry.
AB  - The technique of alpha spectrometry is used to detect alpha particles and to
      determine their energy. In this way the technique is able to provide
      simultaneously quantitative information (i.e. the activity) and qualitative
      information (the identity) on any radionuclide that emits an alpha particle. The
      longer-lived naturally occurring isotopes of thorium are all alpha emitters so
      the technique can be used to quantify them directly and this is extremely
      important if radiation doses due to intakes of these isotopes into the body are
      to be accurately assessed. The principle of the technique is discussed, its
      advantages and disadvantages, and the instrumentation that is commonly used
      today. The need for radiochemical separation is discussed and illustrated by
      reference to analysis procedures in current use for thorium isotopic analysis.
      Practical issues such as detection limits, quality control procedures. sample
      throughput and cost will be covered.

PMID- 11843351
TI  - Determination of thorium by ICP-MS and ICP-OES.
AB  - Natural thorium (232-Th) has traditionally been measured by radiometric
      techniques such as alpha and gamma spectrometry. However. with both ICP-OES and
      ICP-MS instruments becoming relatively common in many analytical laboratories.
      these techniques have become more acceptable in thorium analysis. This paper will
      briefly describe an overview of the instrumentation currently available and the
      techniques themselves applied to thorium analysis. Both techniques have low
      detection limits and require little sample treatment after the sample digestion.
      Routine sample analysis time is short and spectra easy to interpret. usually
      giving results with low uncertainties, Whereas ICP-OES measures total thorium
      only, ICP-MS also offers the potential to measure other long-lived thorium
      isotopes (t 1/2 > 10(4) years), such as 232Th. However, other important isotopes,
      such as 228Th. are still out of reach for routine analysis. The main disadvantage
      of the techniques is the requirement for a sample digestion stage.

PMID- 11843352
TI  - Determination of 232Th by neutron activation analysis using isotope-related ki
      factors.
AB  - Neutron activation analysis was applied to determine the 232Th activity in
      different matrices. Since in nature thorium consists of almost 100% of the long
      lived 232Th, the instrumental trace element analysis method of neutron activation
      analysis can be applied to determine the thorium content in a sample. which can
      then be converted into the corresponding specitic activity. For the analysis
      about 100 mg of the sample was irradiated at a thermal neutron flux of phi(th) =
      8 x 10(13) n.cm(-2) x s(-1). After irradiation the activity of the indicator
      nuclid 232Pa--produced by the (n,gamma) reaction--was measured by gamma
      spectrometry. The content of thorium was calculated using the activation equation
      and the isotope-related ki constant. Finally, the concentration of thorium in the
      sample was converted into the specific activity. The activities of 232Th measured
      by applying neutron activation analysis in different samples were compared with
      the results found by a spectrometry and gamma spectrometry for the daughter
      nuclides 228Ac and 224Ra.

PMID- 11843353
TI  - Separation and measurement techniques for the determination of 228Th, 230Th and
      232Th in various matrices.
AB  - Three analytical techniques are presented which are used at PSI for determination
      of U and Th isotopes (234U, 235U, 238U, 228Th, 230Th, 232Th) in different
      materials, i.e. environmental samples (soils, minerals) and dental ceramics as
      well as in urine for in vitro monitoring of potentially exposed workers.
      Depending on the sample quantity available and/or required detection limits the
      measurements are performed either directly via gamma spectrometry or via alpha
      particle counting with preceding separation chemistry. The separation methods
      applied are based on either extraction chromatography or on sorption of U and Th
      on actinide selective resin. Following sample digestion, chemical yield spike
      additions (232U, 225Th or 225Th), chemical purification and electro-depositional
      source preparation, alpha particle measurement is carried out using low-level
      alpha spectrometry. This technique allows detection limits of less than 0.2 mBq
      per counting source if the assay lasts over a few days and is therefore suitable
      for determination of trace quantities of short-lived 225Th that can be hardly
      detected by means of mass spectrometric techniques.

PMID- 11843354
TI  - Nuclear data used in the analysis of thorium in the workplace.
AB  - The analysis of thorium in the workplace can be achieved using a variety of
      metrological techniques. The uncertainty on the final measured values will
      include components that arise from the uncertainties in the nuclear data that are
      used. These data include half-lives, branching ratios and gamma ray emission
      probabilities. It is important that a common, consistent and reliable data set is
      used in order to minimise the potential differences between analytical results.
      With particular reference to the problems associated with thorium analysis, some
      of the various sources of nuclear data are discussed and a recommended set of
      data is proposed.

PMID- 11843355
TI  - Thorium in the workplace: the preparation and validation of comparison samples
      for a European-based measurement comparison project.
AB  - The quality of any comparison exercise depends critically on the quality.
      accuracy and fitness for purpose of the comparison samples. The comparisons were
      designed to move progressively from the testing of the analysis capabilities for
      relatively simple. aqueous solutions through to the more complex natural matrix
      materials encountered in the workplace. In each case, it was imperative that the
      comparison samples were prepared and validated in such a way as to ensure
      traceability of their activity values to national and international standards of
      radioactivity, to enable a reasonable estimate to be made of the uncertainty on
      those values and to ensure homogencity both within and between samples. The
      processes involved are discussed.

PMID- 11843356
TI  - Thorium in the workplace: results from a European-based measurement comparison
      project.
AB  - A Series of comparisons were conducted to test the capabilities of a range of
      metrological techniques and analytical laboratories engaged in the assay of
      thorium in the workplace. The results of these exercises are presented together
      with the decision criteria used to determine whether results are significantly
      different from the true value. The discussion highlights those aspects which
      warrant closer and further attention.

PMID- 11843357
TI  - Distribution of natural thorium in the tissues of a whole body.
AB  - The distribution of thorium in the tissues of a whole body donor to the United
      States Transuranium and Uranium Registries is described. This case, identified by
      the USTUR as Case 0212, had two documented intakes of plutonium and americium
      from occupational accidents while employed at Hanford but no known occupational
      exposure to thorium. Concentrations of 239+240Pu, 241Am, and 232Th in the tissues
      are compared and the distribution of these isotopes in this case is evaluated.
      The distribution data for 232Th are compared to those from previous studies of
      thorium in human tissues resulting from environmental exposure and to an
      individual exposed to Thorotrast (colloidal ThO2) in a medical diagnostic
      procedure. The 232Th distribution data from this work are also compared against
      ICRP 30 and ICRP 69 models for the behaviour of thorium in the human body.

PMID- 11843358
TI  - In vitro dissolution characteristics of aged and recrystallised high-fired
      232ThO2.
AB  - The dissolution characteristics of 232Th from ThO2 in the lung have been
      determined in an in vitro study. Two types of ThO2 were examined to determine if
      the age of the material had any effect; an aged high-fired ThO2 that had its
      progeny in secular equilibrium, and a recently recrystallised and high-fired ThO2
      in disequilibrium. The results show the amount of 232Th that dissolved from the
      aged ThO2 was approximately 10 times greater than the amount that dissolved from
      the recrystallised and fired ThO2 which was the result of recoil damage to the
      crystal structure of the aged material. A model based on nuclear track theory was
      developed to relate the size of the observed rapidly soluble fraction of 232Th to
      the age of the material and its experimentally determined surface area.

PMID- 11843359
TI  - Ultra low-level gamma ray spectrometry of thorium in human bone samples.
AB  - Following the use of in vivo measurements of 210Pb to estimate retrospectively
      radon exposure, interest has been expressed in the use of in vivo measurements of
      208Tl to estimate thorium intake. To aid with calibration and to determine the
      optimum part of the body on which in vivo measurements should be made, the
      distribution of 208Tl and 228Ac amongst different human bones was measured in the
      underground laboratory HADES. The 208Tl activity was determined by the 2614.5 keV
      and the 583.2 keV gamma ray lines. The 225Ac activity was determined by the 911.2
      keV and the 969.0 keV gamma ray lines. The background under those peaks when
      measured on the 106% relative efficiency coaxial HPGe detector in HADES is of the
      order of 1 d(-1), resulting in detection limits in the order of 1 mBq for both
      radionuclides for a typical 10 g bone sample and for a measuring time of I week.

PMID- 11843360
TI  - The in vivo assessment of thorium body burden by gamma ray sepctrometry.
AB  - Thorium is used in many different industrial technologies and is widely found in
      nature. Internal contamination with thorium is considered as highly hazardous
      because of its radiological and chemical toxicities, which depend on the chemical
      form in which thorium appears. The assessment of the thorium body burden is then
      of primary importance in detecting the risks of personal contamination, and for
      appropriate counteractions when contamination is detected. The in vivo assessment
      of the thorium lung burden is commonly achieved by gamma ray spectrometry of its
      progeny. Three methods for the assessment of thorium in the lungs are compared.
      In the first method, the radionuclide examined is 208Tl, measured with a Nal(TI)
      detector. This simple method can be affected by systematic errors due to 220Rn
      exhalation and because of the assumption of equilibrium between 232Th and 228Th.
      The second method, based on the measurement of the gamma rays emitted by 228Ac,
      requires the use of high-resolution gamma spectrometry (HPGe detectors). The
      accuracy of the thorium quantification is better with this technique. The third
      method is based on the measurement of exhaled 220Rn.

PMID- 11843361
TI  - Thorium in mineral products.
AB  - Many ores contain low levels of thorium. When these ores are processed, the
      associated radioactivity can be found in mineral concentrates, intermediates and
      final products. There is an incentive for industries to remove radioactivity from
      mineral products to allow the movement and sale of these materials, both
      nationally and internationally, without the need for licensing. Control of
      thorium in various products involves the development and optimisation of process
      steps to be able to meet product specifications. The Australian Nuclear Science
      and Technology Organisation (ANSTO) has undertaken a range of R & D programmes
      targeting the treatment of thorium-bearing minerals. This paper discusses the
      application of a microprobe technique for siting radioactivity in zircon and
      ilmenite and the problems experienced in measuring the concentrations in solid
      rare earth products.

PMID- 11843362
TI  - Analysis of thorium and its progeny by gamma ray spectrometry and alpha track
      methods.
AB  - Samples originating from an EU sponsored intercomparison exercise were analysed
      by gamma ray spectrometry (a thorium solution sample, a zircon sand sample and a
      thorium ore sample). An alpha track method was also used to analyse the solution
      sample. The detection efficiency calibration for the gamma ray spectrometry
      measurements on the solid samples was established using an in-house standard of
      thorium nitrate. A GESPECOR Monte Carlo simulation program was utilised in the
      analysis of the solution sample. The in-house thorium nitrate standard was also
      used to prepare standards for the alpha track method. The relative differences
      between the 232Th activity concentration values determined in these
      intercomparison samples and values supplied by the NPL, UK, were found to be less
      than 5% when determined by the gamma ray spectrometry method and less than 8%
      when determined by the alpha track method.

PMID- 11843363
TI  - Thorium determination in intercomparison samples and in some Romanian building
      materials by gamma ray spectrometry.
AB  - Thorium content in zircon sand, thorium ore and a thorium liquid sample (EU
      Laboratories Network Intercomparison), as well as in some Romanian building
      materials: sand, wood, tufa, asbestos-cement. cement mill dust, coal fly ash,
      bricks, and tile (28 samples) was deterimined by gamma ray spectrometry. For the
      building materials, 226Ra, 40K and 137Cs specific activities were also measured.
      The results were compared with the Romanian legal norms concerning the highest
      admissible levels for 232Th, 226Ra. and 40K radioactivity. and to Th, U, and K
      concentration values previously determined in our laboratory on similar types of
      samples.

PMID- 11843364
TI  - Analytical methods for thorium determination: a journey from conventional methods
      to novel applications.
AB  - Thorium may be determined using a variety of analytical methods. These may be
      based on chemical or physical principles or may make use of the radioactive decay
      of the individual thorium isotopes. The method to be used for a certain
      analytical purpose is selected as a function of the matrix of the sample and of
      the concentration of thorium. The present paper describes different
      methodologies, their range of application and discusses selected results. The
      methods described cover a concentration range of more than twelve orders of
      magnitude, i.e. from concentrated solutions to micrometre-sized particles.
      Emphasis is given to active radiometric techniques, chemical and instrumental
      analysis.

PMID- 11843365
TI  - Standard reference materials for thorium analysis.
AB  - Reference materials (RMs) are used in analytical measurements for several
      purposes--to develop and validate analytical measurements, as quality control
      indicators and for calibration. It is therefore essential that suitable reference
      materials are available. Because thorium is usually found in very acid-resistant,
      mineral phases, this becomes even more critical when techniques such as ICP-MS
      are used, which require complete sample digestion. This paper gives an overview
      of the reference materials that are currently available for thorium (232Th and
      other thorium isotopes) in various matrices, sources and indicative costs. The
      IAEA database is identified as a particularly useful source of information, and
      the website address is: http://www.iaea.org/programmes/nahunet/e4/nmrm/index.htm
      A brief summary of the discussion held at the '1st European Workshop on the
      Analysis of Thorium in Workplace Materials', regarding reference materials, is
      given at the end of the paper. A general need for new RMs, specifically for
      workplace materials, was identified as a priority.

PMID- 11843366
TI  - Dosimetric models for thorium and practical problems in assessing intakes.
AB  - An overview is given of the models recommended by the International Commission on
      Radiological Protection (ICRP) for assessing intakes and doses, and summarises
      biokinetic data obtained after the deposition of different chemical compounds of
      thorium in the rat lung. The results emphasise the importance of using material
      specific data rather than default reference values for absorption into blood. The
      limitations of external monitoring of the chest or urine analysis are discussed,
      and comments made on alternative strategies for radiological protection of the
      worker.

PMID- 11843367
TI  - The EC Thematic Network on the Analysis of Thorium and its isotopes in Workplace
      Materials.
AB  - Accurate measurements of workplace exposure to 232Th and its progeny are required
      to estimate internal radiation doses received by persons working with thorium
      containing materials. However, a small intercomparison carried out in the mid
      nineteen nineties raised doubts about the reliability of results obtained by
      methods available for measurement of thorium. An EC-funded thematic network was
      therefore established to bring together experts in the field of thorium analysis
      in order to coordinate research activity and identify best analytical practice.
      requirements for reference materials. etc. This network has now successfully
      completed its work programme. which included a survey to determine future
      research needs; a series of intercomparisons to test the performance of methods
      for measuring thorium in workplace materials, and a workshop held to promote best
      practice and transfer information to regulatory authorities and industry. Results
      of the work have been used to make various recommendations concerning future
      needs in this field.

PMID- 11843368
TI  - Autoimmune thrombocytopenia in women with carcinoma of the uterine cervix
      developing after cisplatin and radiation therapy.

PMID- 11843369
TI  - Uterine torsion due to a fibroid, emergency myomectomy and transverse upper
      segment caesarean section.

PMID- 11843370
TI  - Randomised trial of amnioinfusion during labour with meconium stained amniotic
      fluid.
AB  - OBJECTIVE: To assess the effect of amnioinfusion during labour with meconium
      stained amniotic fluid on caesarean section rate and perinatal outcome. DESIGN:
      Prospective randomised controlled study. SETTING: A tertiary care teaching
      hospital in India. POPULATION: Women in labour at term with meconium stained
      amniotic fluid. METHODS: Two hundred women in labour with > or = 37 weeks
      gestation, single cephalic presentation with moderate or thick meconium were
      randomised to control and amnioinfusion groups at a 1:1 ratio. Amnioinfusion was
      performed using 500 mL of normal saline over a period of 30 minutes in a study
      group. The control group received routine care. Both groups had intermittent
      auscultation of fetal heart rate during labour. MAIN OUTCOME MEASURES: The
      primary outcome measure was caesarean section rate. Secondary outcome measures
      were meconium aspiration syndrome, 1 minute and 5 minute apgar < 7, hypoxic
      ischaemic encephalopathy, neonatal intensive care unit admission, meconium at the
      level of vocal cords. RESULTS: The caesarean section rate in the amnioinfusion
      group was less than the control group (RR 0.47; 95% CI 0.24-0.93). Amnioinfusion
      was associated with a significant decrease in the incidence of meconium at the
      vocal cords (P = 0.001); improvement in 1 minute apgar scores (P < 0.05),
      respiratory distress (P = 0.002) and fewer admissions to nursery compared with
      the controls. This sample size was inadequate to study the impact on meconium
      aspiration syndrome. CONCLUSION: Amnioinfusion in an under resourced labour ward
      decreases caesarean section rates and fetal morbidity.

PMID- 11843371
TI  - Maternal use of cannabis and pregnancy outcome.
AB  - OBJECTIVE: To document the prevalence of cannabis use in a large sample of
      British women studied during pregnancy, to determine the association between
      cannabis use and social and lifestyle factors and assess any independent effects
      on pregnancy outcome. DESIGN: Self-completed questionnaire on use of cannabis
      before and during pregnancy. SAMPLE: Over 12,000 women expecting singletons at 18
      to 20 weeks of gestation who were enrolled in the Avon Longitudinal Study of
      Pregnancy and Childhood. METHODS: Any association with the use of cannabis before
      and during pregnancy with pregnancy outcome was examined, taking into account
      potentially confounding factors including maternal social background and other
      substance use during pregnancy. MAIN OUTCOME MEASURES: Late fetal and perinatal
      death, special care admission of the newborn infant, birthweight, birth length
      and head circumference. RESULTS: Five percent of mothers reported smoking
      cannabis before and/or during pregnancy; they were younger, of lower parity,
      better educated and more likely to use alcohol, cigarettes, coffee, tea and hard
      drugs. Cannabis use during pregnancy was unrelated to risk of perinatal death or
      need for special care, but, the babies of women who used cannabis at least once
      per week before and throughout pregnancy were 216 g lighter than those of non
      users, had significantly shorter birth lengths and smaller head circumferences.
      After adjustment for confounding factors, the association between cannabis use
      and birthweight failed to be statistically significant (P = 0.056) and was
      clearly non-linear: the adjusted mean birthweights for babies of women using
      cannabis at least once per week before and throughout pregnancy were 90 g lighter
      than the offspring of other women. No significant adjusted effects were seen for
      birth length and head circumference. CONCLUSIONS: The results of this study
      suggest that the use of cannabis during pregnancy was not associated with
      increased risk of perinatal mortality or morbidity in this sample. However,
      frequent and regular use of cannabis throughout pregnancy may be associated with
      small but statistically detectable decrements in birthweight.

PMID- 11843372
TI  - Thrombophilia and immunological disorders in pregnancies as risk factors for
      small for gestational age infants.
AB  - OBJECTIVES: To determine if inherited thrombophilia and immunological disorders
      represent risk factors for small for gestational age infants, and to assess their
      relationship with neonatal status. DESIGN: Case-control study. POPULATION: Ninety
      seven consecutive women who had pregnancies complicated by unexplained small for
      gestational age infants, defined as a birthweight below the third centile and 97
      women as controls who delivered infants with a birthweight > or = 10th centile.
      METHODS: Patients were included in the immediate postpartum period and tested for
      antithrombin III, protein C, protein S, anticardiolipin and antinuclear
      antibodies, lupus anticoagulant, Factor V Leiden mutation, prothrombin 20210A
      mutation, and methylenetetrahydrofolate reductase (MTHFR) polymorphism. Women
      with small for gestational age infants were then divided into subgroups depending
      on haemostatic and immunologic status in order to compare neonatal events.
      RESULTS: Frequencies for anticardiolipin and antinuclear antibodies were higher
      in women with small for gestational age infants compared with controls (P = 0.02
      and P = 0.004, respectively), and overall prevalence of inherited thrombophilia
      were comparable in cases and controls (19.6% and 18.6%, respectively). The
      subgroups of patients with small for gestational age infants were women with only
      one inherited thrombophilia (n = 10), only one immunological disorder (n = 14),
      combined disorders (n = 9), and no detected abnormality (n = 64). Admission to
      paediatric ward significantly increased in the group with combined disorders (P =
      0.002) compared with the other groups. Also one-third of the babies from this
      group had a poor neonatal outcome. However, most of the neonatal deaths (6/7 =
      85.7%) occurred in the group with no detected abnormality. CONCLUSION: The
      prevalence of inherited thrombophilia was considered to be similar between the
      case and the control groups even when immunological disorders were significantly
      elevated in pregnancies complicated by the baby being small for gestational age.
      Combined disorders may represent a potential risk factor for severe small for
      gestational age infants. However, the aetiology of small for gestational age
      infants with poor neonatal outcomes remains unknown in most cases.

PMID- 11843373
TI  - Antenatal ultrasound screening for fetal abnormalities: a systematic review of
      studies of cost and cost effectiveness.
AB  - OBJECTIVE: To review systematically and critically evidence to derive estimates
      of costs and cost effectiveness of routine ultrasound screening for fetal
      abnormalities. DESIGN: A systematic review of the literature using explicit
      criteria for inclusion of primary research studies, a stated electronic strategy
      to identify relevant material, and an explanation of why apparently relevant
      studies have not been included. SETTING: All countries of origin were included.
      The results of this review are important to obstetricians and to health service
      managers in the allocation of resources, and others who are considering
      conducting further research in this area. MAIN OUTCOME MEASURE: Formal economic
      evaluations and cost studies of routine ultrasound screening. Costs of routine
      anomaly scans and costs of other procedures carried out as part of antenatal
      screening by ultrasound. RESULTS: One hundred and ninety-nine studies were
      identified in total, 24 reaching the final stage of the review. Nine studies were
      formal economic evaluations and 15 reported costs studies or clinical
      effectiveness studies with some assessment of cost. The studies were carried out
      mainly in Europe and in the United States. After quality criteria were applied,
      data were extracted from six of the economic evaluations and six of the costs
      studies. One economic evaluation conducted alongside a randomised trial concluded
      that screening for fetal abnormalities by ultrasound in the second trimester was
      cost effective, compared with routine antenatal care. The costs of routine scans
      ranged from Pound Sterling 18 to Pound Sterling 204 and for non-routine ranged
      from Pound Sterling 32 to Pound Sterling 113. CONCLUSIONS: There is a lack of
      good quality primary studies of the costs of ultrasound screening in pregnancy.
      Typically, economic evaluations of ultrasound screening have been based on poor
      quality evidence of clinical effectiveness. There is a need for more published
      data on the costs and cost effectiveness of routine ultrasound screening for
      fetal anomalies, and of the longer term consequences of screening for anomalies.

PMID- 11843374
TI  - Violent deaths: the hidden face of maternal mortality.
AB  - OBJECTIVE: To review pregnancy-related deaths due to injuries, to identify the
      characteristics of these women and to compare the magnitude of injury-related
      maternal deaths to that of other causes of maternal death. DESIGN: A
      retrospective study was performed during a five-year period (1991-1995), covering
      deaths from injuries, including suicide, homicide and accidents in Maputo,
      Mozambique. SETTING: Department of Forensic Medicine at the Maputo Central
      Hospital, Mozambique. POPULATION: The pregnant or recently pregnant (post
      abortion and postpartum) population of Maputo city, the national capital of
      Mozambique. Twenty-seven cases of pregnancy-related deaths caused by injuries
      were identified. MAIN OUTCOME MEASURES: Proportion of deaths due to homicide,
      suicide, and accidents in pregnant women or within 42 days after termination of
      pregnancy. RESULTS: Ten cases were due to alleged homicide, nine to alleged
      suicide and six to alleged accident. Fifty-nine percent (16/27) of women
      suffering an injury-related maternal death were younger than 25 years of age.
      Eighty-five percent of pregnancies were less than 28 weeks of gestational age.
      The magnitude of the problem of violence-related maternal deaths compares with
      the magnitude of pregnancy-induced hypertension as the fourth cause of maternal
      death at Maputo Central Hospital. CONCLUSION: The contribution of violence
      related deaths tomaternal mortality is significant and must not be neglected.

PMID- 11843375
TI  - The role of arginine vasopressin in human labour: functional studies, fetal
      production and localisation of V1a receptor mRNA.
AB  - OBJECTIVE: To investigate labour-associated changes in: 1. the myometrial
      contractile response to arginine vasopressin compared with oxytocin in vitro 2.
      fetal production of arginine vasopressin and 3. myometrial vasopressin V1a
      receptor mRNA. DESIGN: The contractile response to vasopressin (compared with
      oxytocin) was investigated in paired myometrial strips in vitro. Blood was taken
      from the umbilical artery and vein at delivery and arginine vasopressin measured
      by radio-immunoassay. V1a receptor mRNA was determined by in situ hybridisation.
      RESULTS: Myometrium was more sensitive to arginine vasopressin than oxytocin
      (P<0.05 for frequency, amplitude and activity integral in paired strips) after,
      but not before labour. There was a marked umbilical arteriovenous difference in
      arginine vasopressin concentration at delivery suggesting fetal production which
      was not influenced by labour. Myometrial vasopressin V1a receptor mRNA was not
      increased after the onset of labour. CONCLUSIONS: The human uterus is extremely
      sensitive to arginine vasopressin in vitro. Arginine vasopressin is produced by
      the fetus but fetal formation is not increased during labour.

PMID- 11843376
TI  - Effect of twin-to-twin delivery interval on umbilical cord blood gas in the
      second twins.
AB  - OBJECTIVE: To examine the effect of twin-to-twin delivery interval on the
      umbilical cord blood gas status of the second twin following vaginal delivery.
      DESIGN: A retrospective study. SETTING: The department of obstetrics and
      gynaecology in a university teaching hospital. POPULATION: Twin deliveries at or
      beyond 34 weeks of gestation over a period of five years, with the first twin
      delivered vaginally. Twins with any antepartum complications including discordant
      growth, intrauterine growth restriction, intrauterine death, fetal malformations
      and pre-eclampsia were excluded. METHODS: The correlation between the twin-to
      twin delivery interval, and both the umbilical arterial and venous blood gas
      parameters of the second twin, including pH, partial pressure of CO2 and base
      excess, were studied. RESULTS: A total of 118 cases were reviewed. The mean
      gestation at delivery was 37.1 weeks. The median twin-to-twin delivery interval
      was 16.5 minutes. There were significant negative correlations between twin-to
      twin delivery interval and both the umbilical cord arterial and venous pH and
      base excess of the second twin (P <0.05). There were also significant positive
      correlations between both arterial and venous partial pressure of CO2 and the
      delivery interval (P <0.05). Similar changes were found even if the analyses were
      limited to those who had normal vaginal deliveries. The umbilical arterial pH of
      Twin 2 was <7.00 in none of the cases delivered within 15 minutes of the birth of
      Twin 1, 5.9% if within 16-30 minutes, and 27% if more than 30 minutes. Among
      those with an inter-twin delivery interval of more than 30 minutes, 73% had
      cardiotocographic evidence of fetal distress which required operative delivery.
      CONCLUSIONS: Umbilical cord arterial and venous values of pH, partial pressure of
      CO2 and base excess of the second twin deteriorate with increasing twin-to-twin
      delivery interval. Risks of fetal distress and acidosis in the second twin are
      high when the twin-to-twin delivery interval is beyond 30 minutes.

PMID- 11843377
TI  - Oral versus intra-vaginal imidazole and triazole anti-fungal agents for the
      treatment of uncomplicated vulvovaginal candidiasis (thrush): a systematic
      review.
AB  - OBJECTIVES: To compare the relative effectiveness, cost effectiveness and safety
      of oral versus intra-vaginal anti-fungal treatments for uncomplicated
      vulvovaginal candidiasis (thrush) and establish patient preference for the route
      of anti-fungal administration. DESIGN: A systematic review of studies comparing
      oral and intra-vaginal anti-fungal treatments for uncomplicated vulvovaginal
      candidiasis. Standard Cochrane Collaboration methods were used. DATA SOURCES: The
      following sources were searched: the Cochrane Controlled Trials Register; the
      Cochrane Sexually Transmitted Disease review group Specialised Register of
      Controlled Trials; EMBASE (January 1980 to January 2000); and MEDLINE (January
      1985 to May 2000). The reference list of each trial was checked for additional
      references. The manufacturers of anti-fungal treatments in the UK were asked for
      information on trials fulfilling the inclusion criteria. METHODS: There was
      duplicate, independent examination and selection of the electronic search results
      followed by duplicate data abstraction. Disagreements regarding inclusion status
      and data abstraction were resolved by discussion between reviewers and the editor
      of the Cochrane Sexually Transmitted Disease group. Randomised controlled trials
      conducted worldwide and published in any language were included. The primary
      outcome measure was clinical cure. Mycological cure, patient preference and
      safety were secondary outcome measures. RESULTS: Seventeen trials were included
      in the review, reporting 19 oral versus intra-vaginal anti-fungal treatment
      comparisons. No statistically significant differences were shown between oral and
      intra-vaginal anti-fungal treatment for clinical or mycological cure. All 10
      trials that reported a preference favoured oral treatment (compared with intra
      vaginal or no preference). No trials presented cost data. CONCLUSIONS: There is
      no difference between the relativeeffectiveness of oral and intra-vaginal anti
      fungal treatment for thrush.

PMID- 11843378
TI  - Women's perceptions and experiences of routine enquiry for domestic violence in a
      maternity service.
AB  - OBJECTIVE: A qualitative study examining women's perceptions and experiences of
      routine enquiry for domestic violence in a maternity service. DESIGN: Purposive
      sampling was used to select a sub-sample from a larger group of women who
      participated in a domestic violence in pregnancy screening study undertaken at
      Guy's and St Thomas' Hospitals in London. SETTING: Interviews were conducted in
      women's homes and general practitioner's surgeries. SAMPLE: Ten women who
      experienced domestic violence in the last 12 months (including pregnancy), six
      women who experienced domestic violence in the last 12 months, but not in
      pregnancy, and 16 women with no history of domestic violence. METHODS: Semi
      structured interviews conducted during the postpartum period (up to 14 months).
      MAIN OUTCOME MEASURES: Women's views on the acceptability and relevance of
      routine enquiry for domestic violence. RESULTS: Routine enquiry for domestic
      violence in maternity settings is acceptable to women if conducted in a safe,
      confidential environment by a trained health professional who is empathic and non
      judgemental. The effectiveness of routine enquiry to elicit a history of domestic
      violence is influenced by factors such as lack of time, confidential consulting
      time, continuity of care, training and availability of resources. CONCLUSIONS:
      Further research is needed to determine whether the use of on-site specialist
      domestic violence workers will increase midwives' ability to routinely enquire
      about domestic violence.

PMID- 11843379
TI  - Risk of partial and complete hydatidiform molar pregnancy in relation to maternal
      age.
AB  - All cases of first histologically confirmed complete and partial moles registered
      between 1985 and 1999 were identified from the database of a Trophoblastic
      Disease Registration Centre. The maternal age distribution at diagnosis was
      calculated for the 7916 molar pregnancies and compared with the maternal age
      distribution of an unselected population of women from a routine obstetric
      database. Likelihood ratios were calculated for complete and partial molar
      pregnancies by maternal age. A positive relationship was found between the risk
      of molar pregnancy and both upper and lower extremes of maternal age (> or = 45
      years and < or = 15 years, respectively). This association, although present for
      both complete and partial moles, is much greater for complete mole at all
      maternal ages, and the degree of risk is much greater with older (> or = 45
      years) rather than younger (< or = 15 years) maternal age. This study provides,
      for the first time, data regarding specific risk of partial versus complete
      hydatidiform mole with maternal age.

PMID- 11843380
TI  - Breast and pelvic examination in women taking hormone replacement therapy.

PMID- 11843381
TI  - Human papillomavirus and cervical cancer: where are we now?

PMID- 11843382
TI  - Overview of the relationship between use of progestogen-only contraceptives and
      bone mineral density.
AB  - OBJECTIVES: To summarise the available epidemiological evidence regarding the
      relationship between the use of progestogen-only contraceptives and bone mineral
      density. DESIGN AND METHODS: Overview of the published epidemiological
      literature. RESULTS: Overall, 17 studies of the use of progestogen-only
      contraceptives and bone mineral density were identified, involving 1529 women
      exposed to progestogen-only contraceptives and 2086 controls. Sixty-eight percent
      of the data relate to the effects of use of depot medroxyprogesterone acetate.
      Average bone mineral density was reduced in current users of depot
      medroxyprogesterone acetate compared with non-users, although density in users
      was within one standard deviation of the mean in non-users. There was significant
      heterogeneity between the results of different studies (P < 0.0001). The
      reduction in bone mineral density appeared to be greater at the lumbar spine,
      femoral neck and ultradistal forearm than at the midshaft of the ulna. Studies
      involving women with a longer average duration of use of depot
      medroxyprogesterone acetate displayed greater reductions in bone mineral density
      compared with studies of women with shorter durations of use. Based on limited
      data, no difference in bone mineral density was observed between former and never
      users of depot medroxyprogesterone acetate. Results regarding the effect of
      levonorgestrel implants were conflicting. Studies of progestogen-only oral
      contraceptives and the progesterone vaginal ring were small and restricted to
      lactating women. CONCLUSIONS: Women currently using depot medroxyprogesterone
      acetate have a lower average bone mineral density than non-users. The magnitude
      of this effect is uncertain but appears to be greater with longer durations of
      use.

PMID- 11843383
TI  - Five-year follow up of women randomised to medical management or transcervical
      resection of the endometrium for heavy menstrual loss: clinical and quality of
      life outcomes.
AB  - OBJECTIVE: To assess clinical status, changes in health related quality of life,
      and subsequent management five years after medical management or transcervical
      resection of the endometrium for treatment of heavy menstrual loss. DESIGN: Five
      year follow up using postal questionnaires and operative databank review.
      SETTING: Gynaecology department of a large UK teaching hospital. POPULATION:
      Women referred to the gynaecologist for treatment of heavy menstrual loss.
      METHODS: Eligible women, without a treatment preference, were randomised equally
      to either medical treatment or transcervical resection of the endometrium. MAIN
      OUTCOME MEASURES: Women's satisfaction with treatment, menstrual status, changes
      in health related quality of life, and additional treatments received at five
      years. RESULTS: One hundred and forty-four patients completed questionnaires,
      achieving 77% follow up (medical n = 71/94; transcervical resection of the
      endometrium n = 73/93). At five-year follow up, 7/71 (10%) of those randomised to
      the medical arm still used medical treatment, while 72/94 (77%) had undergone
      surgical treatment and 17/94 (18%) a hysterectomy. Twenty-five (27%) women
      allocated to transcervical resection of the endometrium had undergone further
      surgery, 18/93 (19%) a hysterectomy. At five years women initially randomised to
      medical treatment were significantly less likely to be totally satisfied (P <
      0.01, difference 21%, 95% CI -37% to -4%), or to recommend their allocated
      treatment to a friend (P < 0.001, difference 59%, 95% CI -73% to -45%). Bleeding
      and pain scores were similar in both groups and highly significantly reduced.
      Significantly more women in the transcervical resection of the endometrium arm
      had no bleeding or very light bleeding (P < 0.02, difference -22%, CI -31% to 
      4%), and they had significantly less days heavy bleeding (P < 0.02). Short Form
      36 health survey scores were significantly improved from baseline for all eight
      health scales in the transcervical resection of the endometrium arm, and four in
      the medical arm. CONCLUSIONS: A policy of immediate transcervical resection of
      the endometrium for women referred to a gynaecologist for treatment of heavy
      menstrual loss achieves higher levels of satisfaction, better menstrual status,
      and greater improvements in health related quality of life than medical
      treatment. In addition, transcervical resection of the endometrium is safe and
      does not lead to an increase in the number of hysterectomies. An effective
      endometrial ablative technique should be offered to all eligible women seeking
      treatment of their heavy menses from a gynaecologist.

PMID- 11843384
TI  - The clinical application of a dual head gamma camera with coincidence detection
      in 20 women with suspected ovarian cancer.
AB  - OBJECTIVE: To assess the effectiveness of a dual head coincidence gamma camera in
      identifying ovarian cancer as a less expensive alternative to the traditional 2
      [18F] fluoro-2-deoxy-D-glucose (18FDG) system using positron emission tomography.
      DESIGN: Prospective study. POPULATION: Twenty consecutive women suspected of
      having ovarian carcinoma. Inclusion was based on abnormal serum CA125 (reference
      range is 0-35 units/L), ultrasound, computerised tomography or clinical findings.
      METHODS: Women underwent assessment before staging laparotomy. Two nuclear
      medicine physicians, who were blinded to the pre-operative assessment, reported
      on 18FDG- dual head coincidence gamma camera imaging. MAIN OUTCOME MEASURES: The
      histology and operative staging were compared with the 18FDG- dual head
      coincidence gamma camera findings. RESULTS: Twelve women had pelvic malignancies
      (nine primary and three recurrences), seven women had benign pathology and one
      patient had a borderline malignancy. We were able to image accurately all
      malignant pelvic masses with dual head coincidence gamma camera, as well as
      accurately demonstrate disease spread. Two of the benign pelvic masses localised
      18FDG. The positive predictive value for detecting malignancy was 86%.
      CONCLUSIONS: Dual head coincidence gamma camera offers accurate and affordable
      imaging in suspected ovarian masses, with improved specificity over CA125,
      ultrasound and computerised tomography. These results are similar to those
      obtained on more expensive dedicated PET systems. We report on a series of
      patients believed to have primary or recurrent carcinoma and recognise the need
      to include patients more likely to have benign lesions to assess false positive
      results. However, we believe that dual head coincidence gamma camera is useful in
      the pre-operative assessment of women with suspected ovarian cancer.

PMID- 11843385
TI  - Comparability of published perinatal mortality rates in Western Europe: the
      quantitative impact of differences in gestational age and birthweight criteria.
AB  - OBJECTIVE: To quantify the impact of publication criteria on differences in
      published national perinatal mortality rates among Western European countries.
      DESIGN: Descriptive study of perinatal mortality rates in Western European
      countries with adjustments for international differences in publication data.
      POPULATION: All live births and perinatal deaths in 1994 in Western European
      countries. METHODS: The 1994 perinatal mortality rates were obtained from
      national and Eurostat publications for Belgium, Denmark, Finland, France,
      Germany, Greece, The Netherlands. Norway, Portugal, Spain, Sweden, United Kingdom
      (England, Wales, Scotland, Northern Ireland). Two methods, one direct and one
      indirect, were used for adjusting these officially published rates for
      differences in registration laws or publication practices. For the indirect
      method adjustment factors were derived from an analysis of a large Finnish
      database using different cutoff points for gestational age and birthweight. For
      the direct method a common cutoff point was imposed for birthweight (1000g) and
      gestational age (28 completed weeks) on national perinatal mortality data,
      obtained from civil registration or hospital/obstetrics databases in each
      country. RESULTS: The published perinatal mortality rates ranged from 5.4 per
      1000 total births in Sweden and Finland to 9.7 in Greece and Northern Ireland.
      The indirect adjustment method showed that some countries apply cutoff points for
      registration or publication of perinatal mortality which may raise the perinatal
      mortality rate by up to 17% above the most commonly used threshold for including
      live and stillbirths. The direct adjustment method showed that a common lower
      limit of 1000g for birthweight or 28 weeks for gestational age would reduce the
      perinatal mortality rate, but by a differing extent ranging from 14% to 40%. Both
      adjustment methods reduced the contrast between the countries' perinatal
      mortality rates, and changed their rank order. CONCLUSION: These quantitative
      results confirm that international differences in countries' published perinatal
      mortality rates partly reflect differences between countries' criteria for
      registration and publication of perinatal deaths.

PMID- 11843386
TI  - Outcome for children born after in utero laser ablation therapy for severe twin
      to-twin transfusion syndrome.
AB  - OBJECTIVE: To examine the postnatal development of a group of children born after
      in utero laser ablation therapy for severe twin-to-twin transfusion syndrome.
      DESIGN: Retrospective cohort outcome study involving assessment of
      neurodevelopment and physical well being. SETTING: Harris Birthright Centre,
      King's College Hospital, London. PARTICIPANTS: Twins and singleton survivors
      treated via laser ablation therapy for twin-to-twin transfusion syndrome over a
      four-year period. METHODS: Of 54 families contacted to participate in the study,
      who had been treated for twin-to-twin transfusion syndrome during a four-year
      period, 24 families attended for paediatric assessment; 12 pairs of twins and 12
      singleton survivors were assessed for perinatal, neurological and
      neurodevelopmental outcome using the Griffiths scales of mental development. A
      further 20 families were assessed via a proforma after contact with their general
      practitioner. A comparison of these groups showed no significant differences in
      sociodemographic factors or severity of disease between responders (44 families,
      81.5%) and non-responders (10 families). RESULTS: The group of children assessed
      by a paediatrician had low birthweight (1619g donor, 1814g recipient, 1877g
      singleton) and had been born preterm (33 weeks twins, 31.2 weeks singleton) with
      attendant increased resuscitation, neonatal unit admission (mean 40 days) and
      instrumental delivery. Mean Griffiths scores were within the normal range of
      ability (91.2 donor vs 97.7 recipient and 101.6 singletons) with the only
      significant difference being in the locomotor subscale where donor (82.6) and
      recipient (85.3) were less than singletons: -99.1 (P < 0.05). There was no
      cerebral palsy in the singleton survivors, but there were five cases in the twin
      group. All except one affected child (with quadriplegia) had mean Griffiths
      scores in the normal range. In the GP proforma group there was one case, in a
      twin, of cerebral palsy. CONCLUSION: The overall cerebral palsy rate was 9%: 0%
      in the singleton survivors group and 13.3% in the twin survivors group. This
      pilot data highlights the need for careful long term follow up of children
      affected by twin-to-twin transfusion syndrome.

PMID- 11843387
TI  - Factor V Leiden and G20210A prothrombin mutations are risk factors for very early
      recurrent miscarriage.
AB  - OBJECTIVE: To determine whether there is an association between early recurrent
      miscarriage (before 10 weeks of pregnancy) and Factor V Leiden and G20210A
      prothrombin mutations. DESIGN: A prospective study. SETTING: Department of
      Gynaecology and Obstetrics, Saint Antoine Hospital, Paris, France. POPULATION:
      Two groups of women: those with early unexplained recurrent miscarriage before 10
      weeks of pregnancy (n = 260) and control healthy women without a previous history
      of thromboembolism (n = 240). METHODS: Screening for defects in the protein C
      anticoagulant pathway was performed using the anticoagulant response to
      agkistrodon confortrix venom (ACV test). Protein C and Factor V Leiden mutation
      testing was performed for each low ACV level. Each sample was tested for the
      G20210A prothrombin mutation. RESULTS: Factor V Leiden and G20210A mutations were
      found to be associated with early recurrent spontaneous miscarriage before 10
      weeks of pregnancy, the odds ratios being 2.4 (95% CI 1-5) and 2.7 (95% CI 1-7),
      respectively. Similar results were found whether or not women had had a previous
      live birth. CONCLUSIONS: Early recurrent miscarriage before 10 weeks of pregnancy
      is significantly associated with Factor V or G20210A prothrombin mutations. These
      results indicate a possible role for anticoagulant prevention in these early
      miscarriages.

PMID- 11843388
TI  - Induction of labour with a viable infant: a randomised clinical trial comparing
      intravaginal misoprostol and intravaginal dinoprostone.
AB  - OBJECTIVE: To compare the efficacy and safety of vaginal misoprostol (50 microg)
      with vaginal dinoprostone. DESIGN: Double-blind randomised trial. SETTING:
      Obstetrics Department, Poissy Hospital, France. PARTICIPANTS: 370 patients with
      medical indications for induction of labour. OUTCOME MEASURES: Vaginal deliveries
      within 24 hours, as well as time to vaginal deliveries, caesarean rates, costs,
      and fetal, neonatal and maternal condition. RESULTS: Compared with vaginal
      dinoprostone, vaginal misoprostol resulted in greater efficacy in several areas:
      vaginal delivery within 24 hours; time to vaginal delivery; and vaginal delivery
      within 12 hours. There was a non-significant increase in the caesarean section
      rate for fetal distress in the misoprostol group, but fewer caesarean sections
      for failed induction. Fetal tolerance was similar in the two groups, although
      significantly more neonates had a cord pH <7.20 and (non-significantly) none had
      meconium stained amniotic fluid in the misoprostol group. The incidence of poor
      neonatal outcome was similar in both groups. Subgroup analysis by indication for
      induction showed that the higher rates of arterial cord pH <7.20 and of meconium
      stained amniotic fluid with misoprostol persisted only in possible fetal
      compromise. Poor neonatal outcome was less frequent in the misoprostol group in
      cases of induction for non-fetal indications. CONCLUSIONS: Vaginal misoprostol
      resulted in successful and earlier induction of labour more often than
      dinoprostone, but the safety of misoprostol raises some concern in potentially
      compromised infants. Misoprostol should be preferred to dinoprostone in cases of
      induction for non-fetal indications.

PMID- 11843389
TI  - Body composition and energy metabolism in normotensive and hypertensive
      pregnancy.
AB  - OBJECTIVE: To determine whether the insulin resistance syndrome and altered body
      composition are features of hypertensive pregnancy. DESIGN: Women were recruited
      in the third trimester of pregnancy from the antenatal clinic, day assessment
      unit, and maternity ward of St George Hospital, Sydney. POPULATION: Women with
      pre-eclampsia (n = 12), gestational hypertension (n = 12), essential hypertension
      in pregnancy (n = 11), and normotensive pregnancy (n = 10). METHODS: Energy
      metabolism was assessed by indirect calorimetry to measure basal metabolic rate
      and diet-induced thermogenesis. Body composition was measured as lean body mass,
      total body water and fat mass by bio-electrical impedance. Blood was collected
      for measurement of glucose, insulin and lipid profiles. Insulin resistance was
      indirectly assessed by the insulin and glucose concentrations and diet-induced
      thermogenesis. RESULTS: Women with essential hypertension and gestational
      hypertension were heavier than women with normotensive pregnancies both pre
      pregnancy and in the third trimester, whereas women with pre-eclampsia were
      similar to those with normotensive pregnancy. Women with essential hypertension
      were otherwise similar to normotensive pregnancy but women with gestational
      hypertension had a reduced diet-induced thermogenesis and almost double insulin
      levels. Women with pre-eclampsia had a similar body composition and insulin
      levels but reduced basal metabolic rate, diet-induced thermogenesis and glucose
      levels compared with normotensive pregnancy. CONCLUSIONS: Women who develop
      gestational hypertension, but not pre-eclampsia, are more likely to be
      overweight. Women with essential hypertension are similar to women with
      normotensive pregnancy throughout pregnancy. Both gestational hypertension and
      pre-eclampsia appear to be associated with some degree of insulin resistance,
      greater than that occurring in normal pregnancy.

PMID- 11843390
TI  - The relationships between leptin and inflammatory cytokines in women with pre
      eclampsia.
AB  - OBJECTIVE: To compare maternal serum leptin concentration in women with pre
      eclampsia and women with normal pregnancy, and to evaluate the relationships
      between leptin and several inflammatory cytokines. DESIGN: Prospective clinical
      study. SETTING: University Hospital of Puerto Real, Cadiz, Spain. SAMPLE: Twenty
      seven women with pre-eclampsia and 25 normotensive pregnant women. METHODS:
      Maternal serum levels of TNF-alpha, TGF-beta1, interleukin 6, and leptin were
      measured using a commercially available immunoassay. MAIN OUTCOME MEASURES:
      Maternal serum levels of leptin and its relationship to levels of TNF-alpha, TGF
      beta1 and interleukin 6. RESULTS: Maternal serum leptin levels were higher in
      women with pre-eclampsia, but this difference was of borderline statistical
      significance (median 15.9 ng/mL; interquartile range (5.4-31.9) vs 30.5 ng/mL
      (13.9-64) (P = 0.05). The concentration of maternal serum leptin was correlated
      with pre-gestational and gestational body mass index (r = 0.45, P = 0.03; r =
      0.44, P = 0.04), TNF-alpha concentration (r = 0.57, P = 0.002) and interleukin-6
      level (r = 0.46, P = 0.02) in women with normal pregnancy. In women with pre
      eclampsia, only a significant correlation between maternal serum leptin level and
      TNF-alpha concentration (0.47, P = 0.01) was found. CONCLUSIONS: The level of
      maternal serum leptin is increased and correlates positively with the level of
      TNF-alpha in women with pre-eclampsia. In women with a normal pregnancy leptin
      levels not only correlate with TNF-alpha, but also with IL-6 and body mass index.

PMID- 11843391
TI  - Maternal endothelial soluble cell adhesion molecules with isolated small for
      gestational age fetuses: comparison with pre-eclampsia.
AB  - OBJECTIVE: 1. To evaluate the activation profile of the endothelium in
      pregnancies complicated by small for gestational age fetuses compared with pre
      eclampsia and normal pregnancy, by measuring the plasma levels of soluble
      adhesion molecules soluble E-selectin, intercellular cell adhesion molecule-1 and
      vascular cell adhesion molecule-1. 2. To determine whether soluble adhesion
      molecules were related to the severity of small for gestational age fetuses and
      pre-eclampsia. DESIGN: Observational study. PARTICIPANTS: Sixteen women with
      small for gestational age fetuses; 15 women with pre-eclampsia and 15 healthy
      primigravidae were recruited as controls. METHODS: Plasma levels of soluble E
      selectin, intercellular cell adhesion molecule-1 and vascular cell adhesion
      molecule-1 were measured by ELISA. RESULTS: Compared with the healthy controls,
      soluble E-selectin was significantly increased in both small for gestational age
      fetuses and pre-eclampsia, whereas intercellular cell adhesion molecule-1 and
      vascular cell adhesion molecule-1 were increased only in pre-eclampsia. In the
      small for gestational age fetuses group, soluble E-selectin correlated inversely
      with the ratio between birthweight and the expected normal birthweight (r = -0.4,
      P = 0.007). In the pre-eclampsia group, a significant correlation was observed
      between vascular cell adhesion molecule-1 and blood pressure (r = 0.54, P =
      0.039). CONCLUSIONS: Endothelial activation, reflected by raised levels of
      soluble E-selectin, is a feature of small for gestational age fetuses and is
      correlated with the severity of the disease. Differences in the profile of
      soluble cell adhesion molecules suggest variations in the degrees of endothelial
      activation between pre-eclampsia and small for gestational age fetuses.

PMID- 11843392
TI  - Oxidative stress in the fetal lamb brain following intermittent umbilical cord
      occlusion: a path analysis.
AB  - OBJECTIVE: To evaluate the relative contribution of cord occlusion length
      intervals between occlusions and experimental duration on oxidative stress in the
      fetal lamb brain. DESIGN: Acute, partially exteriorised fetal lambs with
      intermittent total cord occlusion. SETTING: The Vivarium of Westmead Hospital,
      University of Sydney, Australia and The Chinese University of Hong Kong. MAIN
      OUTCOME MEASURES: Arterio-venous differences in the concentration of organic
      hydroperoxides, measured in paired samples of carotid arterial and jugular venous
      blood, as an index of oxidative stress in the brain. METHODS: Thirty-two fetal
      lambs were exposed to graded hypoxia, induced by intermittent total umbilical
      cord compression of 30 seconds, 60 seconds and 90 seconds duration, occurring
      every minute for a total of 27 occlusions over 81 minutes. Three sham experiments
      were also performed. In addition to organic hydroperoxides, carotid arterial
      blood samples were also assayed in 15 animals (two sham) for oxygen saturation,
      pH, hypoxanthine, xanthine and urate concentrations. A causal model for oxidative
      stress was defined: occlusions leading to hypoxia with a rise in hypoxanthine;
      reperfusion during intervals between occlusions leading to the accelerated
      production of xanthine and uric acid and the generation of oxygen free radicals,
      which in turn, are responsible for the rise in lipid peroxidation. Path analysis
      was performed to assess the strength of the relationships between these variables
      and the cord occlusion length, the interval between occlusions and the duration
      of the experiment. RESULTS: Sham experiments showed no change in organic
      hydroperoxide production. Following 30-second umbilical cord occlusions a sixfold
      drop in mean organic hydroperoxides was observed between carotid arterial and
      jugular venous levels. In contrast, following occlusions of 60 seconds duration
      (or longer) a median 20-fold increase in organic hydroperoxide production was
      observed. Path analysis revealed a strong indirect pathway from occlusion length 
      -> hypoxanthine --> urate and weak positive pathways from oxygen saturation -->
      urate and from interval between occlusions --> urate. After accounting for these
      pathways reflecting oxidative stress, a strong direct path remained from time
      from first occlusion --> organic hydroperoxide production. CONCLUSIONS:
      Peroxidation of lipids in the brain occurs under conditions of severe hypoxia and
      reperfusion associated with intermittent umbilical cord occlusions of 60 seconds
      or longer. The path analysis supported the causal model as originally defined,
      with the exception that the indirect pathway via pH was found to be trivial.

PMID- 11843393
TI  - Fetal magnetoencephalography: a non-invasive method for the assessment of fetal
      neuronal maturation.
AB  - OBJECTIVE: To assess the maturation of auditory evoked cortical responses in the
      human fetus using fetal magnetoencephalography. DESIGN: Prospective case series
      over a three-year period. SETTING: Antenatal clinics, university hospital.
      POPULATION: Singleton pregnancies at 29-40 weeks of gestation. METHODS: We used a
      31-channel-SQUID-biomagnetometer in a magnetically-shielded room to perform fetal
      magnetoencephalography. To record auditory evoked fields from the fetal brain we
      applied 500 monotonal bursts generated by a computerised sound generator directly
      to the maternal abdominal wall near the fetal head. The continuously recorded
      data sets were analysed stepwise using a specially developed heart artefact
      rejection software, Fourier filtering, principle component analysis and half
      split analysis of the averaged data. RESULTS: In 36 of 64 examinations we
      detected signals of auditory evoked fields comparable to the P2m component in
      adults. The earliest recording succeeded in the 29th gestational week. The
      latencies of the auditory evoked responses declined during the third trimester
      from 300 ms to nearly 150 ms at term. The maturation of different components of
      the auditory evoked field could be demonstrated from the 31st gestational week
      onwards. CONCLUSION: The maturation of a fetal auditory cortical function using
      fetal magnetoencephalography could be assessed directly for the first time. We
      believe that this method will add information to current indirect methods of
      assessing the normal maturation of the human fetal brain.

PMID- 11843394
TI  - Mass closure: a new technique for closure of the vaginal vault at vaginal
      hysterectomy.
AB  - A variety of methods of management of the vaginal vault have been described, all
      of which maintain certain principles. In techniques that advocate closure of the
      vault, the peritoneum and vaginal epithelium are treated with separate sutures.
      This leaves a potential space above the vaginal closure. We describe a simple
      technique of mass closure which obliterates this space and incorporates the
      pedicles to provide support for the vault. This method may hold potential
      advantages in terms of haemostasis, risk of vault haematoma, and post-operative
      vaginal cuff infections.

PMID- 11843395
TI  - Skull fracture and contralateral cerebral infarction after ventouse extraction.

PMID- 11843396
TI  - Herniation of the amniotic sac into the bladder through a vesico-uterine fistula
      in the 32nd week of pregnancy.

PMID- 11843397
TI  - Ovarian dysgerminoma presenting with hypercalcaemia.

PMID- 11843398
TI  - Resection of recurrent bulky gynaecological side wall malignancy with iliac
      vessel reconstruction.

PMID- 11843399
TI  - Haematocolpos following allogenic bone marrow transplantation for chronic myeloid
      leukaemia.

PMID- 11843400
TI  - An evaluation of the Norwegian Salmonella surveillance and control program in
      live pig and pork.
AB  - Population data and apparent prevalence data from the Salmonella surveillance and
      control program in pigs (NSSCP) from 1998 and 1999 were used in a simulation
      model to evaluate the efficacy of the program. The model consists of three parts:
      modelling of individual prevalence at the abattoir (abattoir part), modelling of
      the number of sampled herds of different sizes when carcasses are randomly
      sampled at the abattoir (sampling strategy part) and finally, modelling of the
      within herd prevalence (within herd part). A total of 136,550 sows and 2,866,550
      finishing pigs slaughtered, 4446 herds and 11 herds positive for Salmonella in
      1994/1995-2000 were included in the abattoir part, sampling strategy part and the
      within herd part of the model, respectively. The abattoir part showed an average
      estimated prevalence of Salmonella in sows and finishing pigs of (median) 0.4% (5
      95 percentiles = 0.03-2%) and 0.1% (0.04-0.2%) respectively. The estimated number
      of infected sow carcasses that entered the market was 502 (37-2157) while the
      estimated number of finishing pig carcasses was 2919 (1218-5771). The probability
      of being sampled for the 10% smallest herds was (mean) 1.9% (1.6-2.2), to 25%
      (24.7-26.5%) for the 10% largest herds. The within herd prevalence was estimated
      to be from 1% to 4% for Norwegian pig herds. The conclusions drawn from this
      evaluation are that the NSSCP does not have any significant consumer protection
      effect, and that the documentation could be done more effectively using the herd
      rather than the individual animal as the unit of sampling. Sampling should focus
      on the larger herds supplying most of the meat on the market and on herds that
      produce breeding sows and piglets and thus can contribute to the spread of
      Salmonella among herds.

PMID- 11843401
TI  - On calculating sterility in thermal preservation methods: application of the
      Weibull frequency distribution model.
AB  - A simple and parsimonious model which originated from the Weibull frequency
      distribution was proposed to describe nonlinear survival curves of spores. This
      model was suitable for downward concavity curves (Bacillus cereus and Bacillus
      pumilus), as well as for upward concavity curves (Clostridium botulinum). It was
      shown that traditional F values calculated from this new model were no longer
      additive, to such an extent that a heat treatment should be better characterized
      by the obtained decimal reduction of spores. A modified Bigelow method was then
      proposed to assess this decade reduction or to optimize the heat treatment for a
      target reduction ratio.

PMID- 11843402
TI  - Accumulation of type A trichothecenes in maize, wheat and rice by Fusarium
      sporotrichioides isolates under diverse culture conditions.
AB  - Toxigenic isolates of Fusarium sporotrichioides were tested for the production of
      type A trichothecenes (T-2 toxin, HT-2 toxin, diacetoxyscirpenol and neosolaniol)
      when grown on three substrates (maize, rice and wheat) under various conditions
      of temperature and water activity in the laboratory for 3 weeks. Trichothecenes
      were determined by high-performance liquid chromatography with fluorescence
      detection, after derivatisation with coumarin-3-carbonyl chloride. This is the
      first time this analytical method has been applied to an extensive study of
      trichothecene accumulation. With minor exceptions, greater trichothecene
      production occurred when samples were incubated at 20 degrees C and moistened
      with 35% water (water activity 0.990) although incubation conditions affected the
      substrates studied in different ways. No correlation between the different pairs
      of trichothecenes was found except for neosolaniol and diacetoxyscirpenol
      (r=0.56). Principal component analysis results show that the data points can be
      grouped in three rough clusters related to cereal type, which points out that the
      composition of these cereals can influence the production of type A
      trichothecenes.

PMID- 11843403
TI  - Bacteriocin production by Enterococcus faecium FAIR-E 198 in view of its
      application as adjunct starter in Greek Feta cheese making.
AB  - Bacteriocin production by Enterococcus faecium FAIR-E 198, isolated from Greek
      Feta cheese, was studied in batch fermentations, under conditions simulating Feta
      cheese preparation. Maximum enterocin activity and growth rate was obtained in de
      Man-Rogosa-Sharpe (MRS) broth at 37 degrees C with controlled pH 6.5. The
      enterocin was produced throughout the growth phase of the microorganism, showing
      primary metabolite kinetics with a peak activity during the mid-exponential
      phase. The use of skimmed milk as substrate revealed low enterocin activity. When
      fermentations were performed in skimmed milk in the presence of rennet, CaCl2,
      and a mixed starter culture, no enterocin activity was observed, although the
      examined strain grew well under the above conditions. Finally, when E. faecium
      FAIR-E 198 was applied as adjunct starter in Feta cheese making, no enterocin
      activity was detected throughout ripening. Results obtained underline the
      frequently underestimated finding that in vitro production by novel
      bacteriocinogenic starter or co-cultures is no guarantee for in situ efficiency.
      It was concluded that the complex food environment thoroughly interferes with
      bacteriocin production levels.

PMID- 11843404
TI  - Reduction of the native microflora on alfalfa sprouts during propagation by
      addition of antimicrobial compounds to the irrigation water.
AB  - Alfalfa and other types of sprouts are known to harbor large populations of
      native microorganisms. As some of these microbes may be causes of reduced shelf
      life of the product (plant pathogens and other spoilage organisms) and sprouts
      may, on occasion, harbor bacteria pathogenic towards humans, the addition of
      antimicrobial compounds to the irrigation water may be warranted. In this study,
      we tested the efficacy of several antimicrobial compounds for reducing the native
      microbial populations on alfalfa sprouts during propagation. These compounds
      included H2O2, peroxyacetic acid+hydrogen peroxide (Tsunami 100), acidified
      NaClO2, NaClO2 (Aquatize), EDTA, Na3PO4 and NaOCl. When added to the irrigation
      water at vanous concentrations, none of the antimicrobial compounds reduced the
      levels of any class of native microflora by more than 1 log10 without evidence of
      phytotoxicity.

PMID- 11843405
TI  - Characterization of Listeria monocytogenes isolates from the meat, poultry and
      seafood industries by automated ribotyping.
AB  - A total of 564 Listeria monocytogenes isolates were characterized by automated
      ribotyping. The samples were taken from equipment, personnel and the environment
      after cleaning procedures and during food processing, as well as from raw
      materials and products from six meat, two poultry and five seafood processing
      plants located in the Faroe Islands, Finland, Iceland, Norway and Sweden.
      Altogether, 25 different ribotypes (RTs) were generated. Two RTs occurred in the
      samples from all three food sectors--meat, poultry and seafood. Four RTs occurred
      in meat and poultry plant samples and other four RTs occurred in meat and seafood
      plant samples. Five RTs occurred only in meat plant samples, five only in poultry
      plant samples and five only in seafood plant samples. Eight of the thirteen
      plants had their own in-house L. monocytogenes ribotype. There was geographical
      differences between the RTs, but no correlation between RTs and food sectors was
      detected. The discrimination power of automated ribotyping was satisfactory to
      trace the contamination sources in the food processing plants clearly indicating
      the sites at which improved cleaning procedures were necessary. In addition, it
      was possible to screen a large number of isolates with two instruments located at
      different institutes and to make a reliable combination of the results.

PMID- 11843406
TI  - Identification of lactic acid bacteria from spoiled, vacuum-packaged 'gravad'
      rainbow trout using ribotyping.
AB  - A total of 296 lactic acid bacteria (LAB) isolated from spoiled, vacuum-packaged
      'gravad' rainbow trout stored at 3 and 8 degrees C were characterised and
      identified using a molecular approach. The isolates were initially grouped
      according to their HindIII restriction endonuclease profiles and further
      identified to species level using an rRNA gene restriction pattern (ribotype)
      identification database. Lactobacillus sakei, L. curvatus and Carnobacterium
      piscicola were the three main species detected. Only one isolate was identified
      as C. divergens. Most of the carnobacteria were found in the samples stored at 3
      degrees C. The relative proportion of L. sakei was higher in the samples stored
      at 8 degrees C.

PMID- 11843407
TI  - Bacteriocin production by Enterococcus faecium RZS C5 is cell density limited and
      occurs in the very early growth phase.
AB  - Enterocins, bacteriocins produced by enterococci, are gaining interest because of
      their antilisterial activity. Enterococcus faecium RZS C5, a natural isolate from
      cheese, produces such a bacteriocin. Generally, bacteriocin production by lactic
      acid bacteria is a growth-associated process which ceases when cell growth starts
      to level off. Remarkably, enterocin production by Ent. faecium RZS C5 seems to be
      limited to the very early growth phase and is switched off at a well-defined cell
      density of 0.4 g cell dry mass (CDM) l(-1). However, at pH values higher than
      6.5, enterocin production displays distinct kinetics. At such pH values,
      enterocin production is reduced but is maintained until the end of the active
      growth phase. The relation with cell concentration suggests that enterocin
      production is part of a severely regulated mechanism. A kinetic model is set up
      for the description of the early enterocin activity peak. Furthermore, the
      influence of pH and temperature on the kinetics of growth and bacteriocin
      production of Ent. faecium RZS C5 was investigated. At pH 6.5, high enterocin
      activity was obtained in the temperature range 20-35 degrees C. At 35 degrees C,
      enterocin activity could only be detected between pH 5.5 and 8.0.

PMID- 11843408
TI  - Prevalence of Salmonella and Campylobacter in retail chicken meat in Spain.
AB  - From February to November 1999, 198 samples of chicken meat for sale in retail
      outlets and supermarkets in nine provinces of Castilla and Leon (Spain) were
      analysed for the prevalence of Salmonella and Campylobacter. Salmonella was
      isolated from 71 (35.83%) of the samples analysed. The predominant serovars were
      S. enteritidis (47.88%), S. hadar (25.35%) and serotype 4,12:b:-(II) (19.71%).
      Other serovars such as S. mbandaka, S. derby, S. virchow and S. paratyphi B were
      isolated in much lower levels. Thermophilic campylobacters were isolated in
      49.50% of the samples studied.

PMID- 11843409
TI  - Occurrence of Clostridium botulinum in fresh and cured fish in retail trade in
      Cochin (India).
AB  - The occurrence of Clostridium botulinum in fresh (67) and cured fish (278)
      samples in retail trade in Cochin was studied. An overall prevalence of 19%
      (13/67) was found in fresh retail fish and types A to D were detected in the
      positive samples. In pelagic fish, incidence of C. botulinum was 18% (7/39)
      whereas in demersal fish, 21% (5/24) of the samples harboured C. botulinum.
      Incidence of C. botulinum in shrimp was 25% (1/4) and type D was found in the
      positive sample. Of 257 cured fish in retail trade tested for the presence of C.
      botulinum, the overall contamination level was 10% (25/257). Among the C.
      botulinum types A to D prevalent in fresh fish, types C and D were the
      predominant types found in cured products. In salt-dried shrimp, of the 21
      samples analysed, 10 samples (48%) harboured C. botulinum.

PMID- 11843410
TI  - Improving artificial neural networks with a pruning methodology and genetic
      algorithms for their application in microbial growth prediction in food.
AB  - The application of Artificial Neural Networks (ANN) in predictive microbiology is
      presented in this paper. This technique was used to build up a predictive model
      of the joint effect of NaCl concentration, pH level and storage temperature on
      kinetic parameters of the growth curve of Lactobacillus plantarum using ANN and
      Response Surface Model (RSM). Sigmoid functions were fitted to the data and
      kinetic parameters were estimated and used to build the models in which the
      independent variables were the factors mentioned above (NaCl, pH, temperature),
      and in some models, the values of the optical densities (OD) vs. time of the
      growth curve were also included in order to improve the error of estimation. The
      determination of the proper size of an ANN was the first step of the estimation.
      This study shows the usefulness of an ANN pruning methodology. The pruning of the
      network is a process consisting of removing unnecessary parameters (weights) and
      nodes during the training process of the network without losing its
      generalization capacity. The best architecture has been sought using genetic
      algorithms (GA) in conjunction with pruning algorithms and regularization methods
      in which the initial distribution of the parameters (weights) of the network is
      not uniform. The ANN model has been compared with the response surface model by
      means of the Standard Error of Prediction (SEP). The best values obtained were
      14.04% of SEP for the growth rate and 14.84% for the lag estimation by the best
      ANN model, which were much better than those obtained by the RSM, 35.63% and
      39.30%, respectively. These were very promising results that, in our opinion,
      open up an extremely important field of research.

PMID- 11843411
TI  - Inhibitory substances produced by Lactobacilli isolated from sourdoughs--a
      review.
AB  - Several sourdough lactic acid bacteria (LAB) produce inhibitory substances other
      than organic acids. Bacteriocins (bavaricin A, and plantaricin ST31), a
      bacteriocin-like inhibitory substance (BLIS C57), and a new antibiotic
      (reutericyclin) have been discovered. Maximum antimicrobial production was found
      in the pH range 4.0-6.0. Temperature optima vary strongly. The substances are
      resistant to heat and acidity, and inactivated by proteolytic enzymes, except for
      reutericyclin. Bavaricin A and plantaricin ST31 have been purified to
      homogeneity. Bavaricin A is classified as a class IIa bacteriocin. Reutericyclin
      is a new tetramic acid. The mode of action of bavaricin A, BLIS C57, and
      reutericyclin is bactericidal. Some of these substances are active towards some
      Bacilli, Staphylococci and Listeria strains. Up to now, only the application
      potential of purified bavaricin A has been examined. More research should be done
      to study the production, the activity, and the stability of these inhibitory
      substances in food systems as these often differ from the broths mostly used in
      this kind of studies. Furthermore, an extensive screening of the sourdough
      microflora must be performed, in particular towards Bacilli and fungi. This could
      lead to the discovery of additional inhibitory substances, although it seems that
      the frequency of isolating bacteriocin-producing sourdough LAB is low. However,
      potent antimicrobials towards Bacilli as well as antifungal substances will have
      to be found using rational screening strategies and novel purification and
      analytical techniques.

PMID- 11843412
TI  - High prevalence of Clostridium botulinum types A and B in honey samples detected
      by polymerase chain reaction.
AB  - A test protocol for reliable detection of Clostridium botulinum types A and B
      spores in honey by polymerase chain reaction (PCR) was developed and used for a
      prevalence survey of C. botulinum spores in 190 honey samples. The inhibiting
      effects of honey on microbial growth and PCR analysis were overcome by using a
      method of supernatant filtration (SF) in the preparation of the samples before
      enrichment and PCR. By using this method, an inoculum of 0.1 spore of C.
      botulinum/g honey could be detected. In the prevalence survey, spores of C.
      botulinum were detected in 8 (7%) of the 114 Finnish and in 12 (16%) of the 76
      imported honey samples. The quantity of spores in PCR-positive samples varied
      from less than 18 to 140 spores/kg. Neurotoxin gene sequences corresponding to C.
      botulinum type A were detected in 17 samples and proteolytic type B in 12 samples
      by PCR analysis. Both types A and B were detected in nine samples. Strains of C.
      botulinum type A were isolated from 14 and type B from 2 of the 20 PCR-positive
      samples. This is the first report of type A spores of C. botulinum being detected
      and isolated in Fennoscandia.

PMID- 11843413
TI  - New efficient amylase-producing strains of Lactobacillus plantarum and L.
      fermentum isolated from different Nigerian traditional fermented foods.
AB  - Amylolytic lactic acid bacteria (ALAB) were isolated from Nigerian traditional
      fermented foods (fufu, burukutu, ogi-baba and kunu-zakki) with the aim of
      selecting efficient amylase-producing strains. Nine isolates were characterized
      on the basis of their phenotypic and taxo-molecular characteristics. Three groups
      could be distinguished by their fermentation profiles and this was confirmed by
      DNA restriction analysis. Though fermentation profiles gave good identification
      of strain K9 (unique representative of group III) as Lactobacillus fermentum,
      they could not be used to ascertain the taxonomic position of strains of groups I
      and II. Analysis of partial 16S rRNA sequences led to the identification of these
      groups as L. plantarum strains and confirmed the species of strain K9 as L.
      fermentum. The two distinct phenotypic groups of L. plantarum differed in their
      use of D-xylose, L-arabinose, melibiose and were different from the previously
      described amylolytic L. plantarum A6 isolated from retted cassava in Congo. L.
      fermentum K9 was different from L. fermentum OgiE1 and Mw2 isolated from Benin
      maize sourdough and it is the first amylolytic L. fermentum described from
      Nigerian fermented products. Enzymatic profiles showed some differences between
      the strains of a similar fermentation group. One of the most relevant
      characteristics of the isolates was a higher yield of amylase production than
      those reported for previously described ALAB grown under the same conditions.
      Furthermore, all isolates were tolerant to an exposure at pH 2 and to bile salts.

PMID- 11843414
TI  - Colony-blot assay with anti-p60 antibodies as a method for quick identification
      of Listeria in food.
AB  - The present study evaluated the ability to isolate Listeria from foods, using
      shortened procedure of sample enrichment followed by immunomagnetic separation or
      filtration methods, and serological identification of isolated bacteria by colony
      blot and Western blot methods with anti-p60 antibodies. By these rapid methods,
      identification of Listeria was achieved in much shorter time (40-48 h) than with
      standard cultivation and biochemical identification procedures. The rapid methods
      used are easy to perform and, what is most important, their specificity is very
      high and fulfills the expectations. The possibility to select Listeria colonies
      growing on non-selective media by blotting with anti-p60 antiserum seems to be
      particularly valuable in examination of food samples containing/not too many
      Listeria (1-10 CFU/25 g). However, the blot method using anti-PepD mAb specific
      to unique region of L. monocytogenes p60 is necessary to distinguish L.
      monocytogenes from other Listeria species.

PMID- 11843415
TI  - Fungal spoilage of bottled mineral water.
AB  - The occurrence of filamentous fungi together with bacteriological parameters was
      assessed in 126 samples of still bottled mineral water of eight different
      commercial brands in Argentina. In spoiled samples with visible mycelium growth,
      the most frequently isolated fungal species were Penicillium citrinum, P.
      glabrum, other Penicillium species, Cladosporium cladosporioides and Alternaria
      alternata. In unspoiled samples, the genera found were Penicillium, Cladosporium,
      Rhizopus, Aspergillus and Phoma. Only three of the 126 samples failed to meet the
      required microbiological standards because they were found to contain faecal
      streptococci.

PMID- 11843416
TI  - Antimicrobial effect of electrolyzed water for inactivating Campylobacter jejuni
      during poultry washing.
AB  - The effectiveness of electrolyzed (EO) water for killing Campylobacter jejuni on
      poultry was evaluated. Complete inactivation of C. jejuni in pure culture
      occurred within 10 s after exposure to EO or chlorinated water, both of which
      contained 50 mg/l of residual chlorine. A strong bactericidal activity was also
      observed on the diluted EO water (containing 25 mg/l of residual chlorine) and
      the mean population of C. jejuni was reduced to less than 10 CFU/ml (detected
      only by enrichment for 48 h) after 10-s treatment. The diluted chlorine water (25
      mg/l residual chlorine) was less effective than the diluted EO water for
      inactivation of C. jejuni. EO water was further evaluated for its effectiveness
      in reducing C. jejuni on chicken during washing. EO water treatment was equally
      effective as chlorinated water and both achieved reduction of C. jejuni by about
      3 log10 CFU/g on chicken, whereas deionized water (control) treatment resulted in
      only 1 log10 CFU/g reduction. No viable cells of C. jejuni were recovered in EO
      and chlorinated water after washing treatment, whereas high populations of C.
      jejuni (4 log10 CFU/ml) were recovered in the wash solution after the control
      treatment. Our study demonstrated that EO water was very effective not only in
      reducing the populations of C. jejuni on chicken, but also could prevent cross
      contamination of processing environments.

PMID- 11843417
TI  - Fusarium toxins in wheat flour collected in an area in southwest Germany.
AB  - A total of 60 samples of wheat flour were collected during the first 6 months of
      1999 from mills and food stores in an area in southwest Germany. Samples included
      whole-grain and two types of white flour with these three groups characterized by
      a high, medium and low ash content. The contents of deoxynivalenol (DON),
      nivalenol (NIV), 3- and 15-acetyldeoxynivalenol, HT-2 toxin (HT-2), T-2 toxin (T
      2) and fusarenon-X (FUS-X) were determined by gas chromatography/mass
      spectrometry, and those of zearalenone (ZEA), alpha- and beta-zearalenol (alpha-
      and beta-ZOL) by high performance liquid chromatography with fluorescence
      detection. FUS-X, alpha- and beta-ZOL were not detected in any sample. Based on
      incidence and level, DON was the predominant toxin followed by NIV and ZEA for
      all three flour types. The overall degree of toxin contamination was lower with
      decreasing ash content. This suggests a localization of the toxins analyzed
      primarily in the outer parts of the original wheat kernels. The median DON
      content was significantly (P<0.05) higher for wheat flour originating from wheat
      of conventional than of organic production.

PMID- 11843418
TI  - Occurrence of xerophilic fungi in bakery gingerbread production.
AB  - The production process of a coconut type of gingerbread was examined for possible
      sources of contamination with xerophilic fungi. In the production flow chart,
      critical control points were found at which some effective steps could be made to
      eliminate undesirable fungal contamination, affected by water activity and
      temperature, and to prevent mould spoilage of the products. The following
      xerophilic fungi were detected, isolated and identified: Eurotium amstelodami, E.
      chevalieri, E. herbariorum, E. rubrum and Wallemia sebi. The resistance of these
      fungi against elevated temperature and preserving agents was investigated. It was
      found that Eurotium species were more resistant than W. sebi. Preservation
      against xerophilic fungi was more effective with the use of propionic acid than
      with potassium sorbate.

PMID- 11843419
TI  - Molecular typing techniques to characterize the development of a lactic acid
      bacteria community on vacuum-packaged beef.
AB  - The development of a community of lactic acid bacteria from vacuum-packaged beef
      was investigated during a 6-week storage trial at 2 degrees C. The lactic acid
      bacteria population was monitored by using molecular techniques to identify a
      random sample of isolates at biweekly intervals during the storage trial. The
      polymerase chain reaction and a randomly amplified polymorphic DNA technique were
      used to identify and distinguish populations of lactic acid bacteria that
      developed during the storage trial. At week 0, the population of lactic acid
      bacteria was 3.5 log cfu/120 cm2 and by week 6, the population reached a maximum
      of 7.6 log cfu/120 cm2. A sampling from the week 0 population indicated a mixed
      community of Lactobacillus curvatus, Lactobacillus sakei and Leuconostoc spp.
      However, the sampling from week 6 indicated the population composition had
      changed to one where a single Leuconostoc strain predominated. This strain
      demonstrated antagonism towards the growth of other lactic acid bacteria isolated
      during the study. Additionally, the strain inhibited the growth of foodborne
      pathogens Escherichia coli O157:H7 and Listeria monocytogenes. DNA sequence data
      from the 16S rRNA gene suggested that the isolate may be a Leuconostoc gelidum
      strain.

PMID- 11843420
TI  - Exposures and their determinants in radiographic film processing.
AB  - Radiographers process X-ray films using developer and fixer solutions that
      contain chemicals known to cause or exacerbate asthma. In a study in British
      Columbia, Canada, radiographers' personal exposures to glutaraldehyde (a
      constituent of the developer chemistry), acetic acid (a constituent of the fixer
      chemistry), and sulfur dioxide (a byproduct of sulfites, present in both
      developer and fixer solutions) were measured. Average full-shift exposures to
      glutaraldehyde, acetic acid, and sulfur dioxide were 0.0009 mg/m3, 0.09 mg/m3,
      and 0.08 mg/m3, respectively, all more than one order of magnitude lower than
      current occupational exposure limits. Local exhaust ventilation of the processing
      machines and use of silver recovery units lowered exposures, whereas the number
      of films processed per machine and the time spent near the machines increased
      exposures. Personnel in clinic facilities had higher exposures than those in
      hospitals. Private clinics were less likely to have local exhaust ventilation and
      silver recovery units. Their radiographers spent more time in the processor areas
      and processed more films per machine. Although exposures were low compared with
      exposure standards, there are good reasons to continue practices to minimize or
      eliminate exposures: glutaraldehyde and hydroquinone (present in the developer)
      are sensitizers; the levels at which health effects occur are not yet clearly
      established, but appear to be lower than current standards; and health effects
      resulting from the mixture of chemicals are not understood. Developments in
      digital imaging technology are making available options that do not involve wet
      processing of photographic film and therefore could eliminate the use of
      developer and fixer chemicals altogether.

PMID- 11843421
TI  - Residential and commercial painters' exposure to lead during surface preparation.
AB  - The California Painters Project was a 2-year intervention research project aimed
      at preventing lead poisoning among a group of residential and commercial painters
      in San Francisco, Calif. As part of this project 12 contractors invited project
      staff to conduct employee exposure monitoring. Twenty-five full-shift samples
      were collected, with 8-hr TWA results ranging from 0.8 to 550 microg/m3
      (arithmetic mean: 57 microg/m3). Six of the 25 samples (24%) were above the
      Occupational Safety and Health Administration (OSHA) permissible exposure limit;
      all of these involved dry manual sanding or uncontrolled power sanding. Fifty
      eight 30-minute task-specific samples also were collected. The arithmetic mean
      concentration results for heat gun use, wet sanding, and open flame burning were
      all under 10 microg/m3; the mean concentration for HEPA-exhausted power sanding
      was 33 microg/m3; dry manual scraping, 71 microg/m3; dry manual sanding, 420
      microg/m3; and uncontrolled power sanding, 580 microg/m3. Analysis and modeling
      based on the 30-min results for dry manual sanding and uncontrolled power sanding
      indicate that painters' full-shift exposures often exceed 500 microg/m3 and the
      OSHA assigned level of protection for a half-mask air-purifying respirator. These
      results are cause for concern because both of these surface preparation methods
      are widely performed wearing half-mask respirators. The data show that HEPA
      exhausted power sanding reduces paint dust exposure levels by approximately 80 to
      90%. These tools should be more widely promoted as a safer alternative work
      method.

PMID- 11843422
TI  - Validity of occupational energy expenditure assessed by interview.
AB  - Measuring physical activity at work has been a field of growing interest in
      recent decades, and there is a need for reliable, standardized assessment
      instruments for application in large population studies. The present study
      examined the validity of a task-oriented interview for assessing energy
      expenditure in occupational work. The interview was developed for use in the
      MUSIC-Norrtalje study, a population study with the overall aim of identifying
      risk and preventive factors for musculoskeletal disorders. Twenty-seven persons
      were included in the study. Each respondent defined all tasks performed during a
      typical workday and estimated their durations. For each task the interviewer then
      assessed the level of energy expenditure in multiples of the resting metabolic
      rate (MET) and calculated a time-weighted average MET (TWA-MET) for a typical
      workday. Measurements of oxygen consumption and observations of duration of each
      work task were performed during 2 workdays in all the interviewed subjects. The
      validity was tested by comparing TWA-MET derived from the interviews with those
      derived from measurements; the product moment correlation coefficient was 0.70.
      The interview may offer sufficient validity for assessment of energy expenditure
      in large population studies.

PMID- 11843423
TI  - Evaluation of an occupational health and safety management system performance
      measurement tool-II: scoring methods and field study sites.
AB  - With the proliferation of occupational health and safety management systems
      (OHSMSs) in the 1990s, an assessment instrument was developed at the University
      of Michigan to measure a wide range of OHSMSs. Due to the range of systems it was
      designed to measure, the instrument is referred to as a universal assessment
      instrument (UAI). This article is part of a series of UAI-related articles and
      presents methods used in the UAI's initial field evaluation efforts. The UAI's
      measurement scale, case study methods, data management methods, and test site
      selection criteria are presented. Three test sites were selected from a pool of
      15 that responded to a study solicitation. The case study methods, measurement
      scales, and data management system were found to be effective in performing the
      initial validation efforts. It is concluded that the qualitative methods used
      were effective in collecting the necessary information to further understand the
      complex nature of management system measurement. Companion articles address the
      actual evaluation assessment.

PMID- 11843424
TI  - Estimation of mean and standard deviation.

PMID- 11843425
TI  - Evaluation of an occupational health and safety management system performance
      measurement tool-III: measurement of initiation elements.
AB  - With the proliferation of occupational health and safety management systems
      (OHSMS) in the 1990s, an assessment instrument was developed at the University of
      Michigan to measure a wide range of OHSMSs. Due to the range of systems it was
      designed to measure, the instrument is referred to as a universal assessment
      instrument (UAI). Initial evaluation of the instrument's first four sections is
      reported here. This study shows that the UAI's initiation measurement criteria
      and measurement scales could make distinctions between the OHS management systems
      at three test sites. This was particularly evident in the case in an organization
      in which a standards-based OHSMS was not implemented. In this case the UAI's two
      measurement scales could distinguish between areas that were being developed
      (development scale) and areas that were in conformance with the measurement
      criteria (conformance scale). The score totals were consistent with the
      qualitative assessment using case study methods during field pilot testing; with
      the exception of Section 2.0, Employee Participation, in which scoring at one
      test site was not consistent with case study findings. It is suggested that the
      variables/measures presented in the UAI's OHSMS initiation organizing category
      may contain performance measures that may serve as key leading indicators of
      overall OHS performance.

PMID- 11843426
TI  - Occupant perception of indoor air and comfort in four hospitality environments.
AB  - This article reports on a survey of customer and staff perceptions of indoor air
      quality at two restaurants, a billiard hall, and a casino. The survey was
      conducted at each environment for 8 days: 2 weekend days on 2 consecutive
      weekends and 4 weekdays. Before and during the survey, each hospitality
      environment satisfied ventilation requirements set in ASHRAE Standard 62-1999,
      Ventilation for Acceptable Indoor Air. An objective of this study was to test the
      hypothesis: If a hospitality environment satisfies ASHRAE ventilation
      requirements, then the indoor air is acceptable, that is, fewer than 20% of the
      exposed occupants perceive the environment as unacceptable. A second objective
      was to develop a multiple regression model that predicts the dependent variable,
      the environment is acceptable, as a function of a number of independent
      perception variables. Occupant perception of environmental, comfort, and physical
      variables was measured using a questionnaire. This instrument was designed to be
      efficient and unobtrusive; subjects could complete it within 3 min. Significant
      differences of occupant environment perception were identified among customers
      and staff. The dependent variable, the environment is acceptable, is affected by
      temperature, occupant density, and occupant smoking status, odor perception,
      health conditions, sensitivity to chemicals, and enjoyment of activities.
      Depending on the hospitality environment, variation of independent variables
      explains as much as 77% of the variation of the dependent variable.

PMID- 11843427
TI  - Effect of rise distance on droplets generated from bubble bursting on the surface
      of chromic acid solutions.
AB  - In the processes of chromium electroplating, bursting bubbles are the major
      sources of chromium droplets that may lead to nasal septum disorders among
      workers. The gas bubbles form as a result of electrochemical reactions on the
      surfaces of pieces being plated, rise through the liquid, and then burst into
      droplets at liquid surfaces. The dimensions of the pieces being plated differ
      from piece to piece, and therefore the rise distance of the bubbles varies. This
      study is aimed at evaluating the effect of rise distance on the characteristics
      of droplets generated from bubbles bursting on the surface of chromic acid
      solutions by an experimental bubbling system. Two rise distances, 15 and 30 cm,
      were tested. An aerodynamic particle sizer was used to determine the droplet size
      distribution over the range of 0.8-30 microm. A Marple personal impactor was
      employed to collect droplet samples on polyvinyl chloride filters for Cr(VI)
      analysis. It was found that the Cr(VI) concentrations in droplets increased when
      the bubble rise distance increased. The result suggests that soluble ions such as
      Cr(VI) are scavenged by rising bubbles.

PMID- 11843428
TI  - A new direction in low-back pain research.
AB  - This article suggests reasons for the difficulty in understanding and preventing
      low-back pain (LBP), provides a framework for understanding the causes of
      reported LBP, and highlights an important new direction in research that could
      accelerate progress in reducing LBP. Fundamental to understanding LBP is the
      recognition that it is a symptom not an underlying condition. Worker reports of
      LBP depend not only on the extent and nature of underlying injury but also the
      worker's perceptions and the likelihood of reporting the symptoms. Each of these
      factors, in turn, depends on a number of other proximal and distal factors.
      Identifying the root causes of underlying injury is essential to improving
      prevention programs. Yet, many of the methods used to study LBP and its causes
      have serious shortcomings, adding to the confusion over appropriate preventive
      strategies. An important gap in LBP research has been the factors influencing
      preventive behaviors for both workers and managers. If workers or managers
      attribute the causes of LBP to the wrong factors, preventive behaviors will be
      misdirected and ineffective. Attribution theory, a relatively recent application
      in the occupational health field, offers promise for identifying incorrect
      attributions and modifying these attributions so that appropriate protective
      actions are taken.

PMID- 11843429
TI  - A comparative analysis of glove permeation resistance to paint stripping
      formulations.
AB  - Although there is a wide variety of work gloves available to users of commercial
      paint stripping products, there are no published studies examining which type of
      gloves provide the best protection. To address this need, a multiphase study was
      undertaken to evaluate how several types of gloves resist multichemical-based
      paint stripping formulations. Due to the wide range of commercial paint stripping
      formulations available, seven categories of surrogate paint stripper formulations
      were created to evaluate glove performance initially. Twenty different glove
      types were identified for initial evaluation. Degradation resistance screening
      was carried out for each glove style and paint stripping formulation. Screening
      results were used to identify those glove styles least affected by the surrogate
      paint strippers. Those gloves were then evaluated for their resistance to
      permeation using continuous contact testing based on ASTM Test Method F 739.
      Glove styles showing extensive permeation with early breakthrough were then
      evaluated to see how they performed with only intermittent contact with the
      surrogate paint strippers using a modified form of ASTM Test Method F 1383. These
      results were used to select glove styles to be tested using commercially
      available paint stripping products. Gloves made of plastic laminate and butyl
      rubber were the most effective against the majority of paint strippers. More
      glove styles resisted permeation by N-methylpyrrolidone and dibasic ester-based
      paint strippers than conventional solvent products such as methylene chloride,
      methanol, isopropanol, acetone, and toluene. The study also found that decreased
      contact time caused relatively little change in permeation resistance and that
      the surrogate paint stripper data did not always accurately predict resistance to
      the commercial paint stripper formulations.

PMID- 11843430
TI  - Assessment of the effectiveness of respirator usage in coke oven workers.
AB  - This program protection factor study was conducted to evaluate the effectiveness
      of filter cartridge respirators while coke oven workers performed their normal
      work. Benzene soluble fraction (BSF) of total particulate concentrations was
      measured inside and outside the respirators of nine coke oven workers who worked
      on the top of the battery of one older coke oven plant and who reported regular
      use of respirators. The measurements were taken for 3 consecutive days. Excluding
      two undetectable measurements inside the respirator, it was found that the
      outside respirator BSF concentrations (25 sets) ranged from 87 to 807 microg/m3,
      whereas the inside respirator BSF concentrations ranged from 16 to 509 microg/m3.
      A program protection factor (PPF) for each set of observations was calculated as
      the ratio of outside to inside air BSF concentrations. The mean PPF was 2.5 with
      a range of 1.1 to 9.6, and 12 of the 25 measurements (48%) were below 2.0.
      Although the workers claimed they regularly wore their respirators, the wide
      range and the low PPF findings suggest that worker behavior and respirator fit
      may influence the level of protection provided by the respirator.

PMID- 11843431
TI  - Preliminary assessment of worker and ambient air exposures during soil
      remediation technology demonstration.
AB  - Hazardous waste site remediation workers or neighboring residents may be exposed
      to particulates during the remediation of lead-contaminated soil sites.
      Industrial hygiene surveys and air monitoring programs for both lead and dust
      were performed during initial soil sampling activities and during pilot scale
      technology demonstration activities at two lead-contaminated soil sites to assess
      whether worker protection or temporary resident relocation would be suggested
      during any subsequent remediation technology activities. The concentrations of
      lead and dust in the air during pilot scale technology demonstration studies were
      within applicable exposure guidelines, including Occupational Health and Safety
      Administration permissible exposure limits, National Institute for Occupational
      Safety and Health recommended exposure limits, American Conference of
      Governmental Industrial Hygiene threshold limit values, and the United States
      Environmental Protection Agency's National Ambient Air Quality Standards program
      limits.

PMID- 11843432
TI  - ELPAT Program report: background and current status. Environmental Lead
      Proficiency Analytical Testing.

PMID- 11843433
TI  - AIHA consultants listing. American Industrial Hygiene Association.

PMID- 11843434
TI  - Surveillance systems for pesticide intoxications.
AB  - The intent of this article is to provide an overview of surveillance systems
      dealing with pesticide intoxications. Surveillance, medical monitoring, and the
      components of a surveillance system are discussed. Information is presented on
      how to make a diagnosis of environmental or occupational pesticide intoxication,
      examples of different case definitions, and the steps in investigating a
      pesticide disease outbreak. Examples from various countries are used to
      illustrate acute pesticide intoxication surveillance, pesticide exposure
      surveillance, and medical monitoring of pesticide-exposed workers. Finally, a
      list of informational sources for pesticide toxicology, medical diagnosis and
      treatment, and surveillance data is provided. It is anticipated that this
      information will assist those individuals or organizations seeking to develop
      such a system, evaluate an existing system, or gain a better understanding of
      data derived from such systems.

PMID- 11843435
TI  - Contact dermatitis caused by pesticides among banana plantation workers in
      Panama.
AB  - To characterize dermatitis related to pesticide exposures among banana plantation
      workers in Panama, the authors studied 281 workers seen at The Occupational
      Health Department of the Social Security Hospital of Changuinola and Puerto
      Armuelles between 1988-1992 and in 1993. Exposure data were collected through a
      standardized occupational health history. Physical examination, a standard patch
      test, and a pesticide patch test (PPT) were carried out. Of the 244 men (86.8%)
      and 37 women (13.2%), 17 and 37, respectively, were packing station workers. The
      other 227 men were field workers, exposed to many pesticides (propiconazole,
      maneb, chlorothalonil, dithane, dalaphon, ametrine; and gramoxone). The 54
      packing station workers were exposed to imazalil, thiabendazole, aluminum
      hydroxide solutions, and formaldehyde. The hands were the most frequently
      affected areas (82%), followed by the thorax and abdomen (9%), legs and feet
      (5%), and genital area (4%). There were 78 positive PPTs (27.8%) in 281 patients.
      The most frequent reactions were to the fungicides chloro-thalonil (51.4%),
      thiabendazole (12.8%), imazalil (10.2%), and aluminum hydroxide (10.2%), which
      accounted for 85% of all positive tests. The majority of the cases were related
      to exposures to fungicides; 246 with negative PPTs were classified as irritant
      contact dermatitis patients; 48 controls were negatives. Contact dermatitis
      related to pesticide exposure is a significant occupational health problem for
      banana workers in Panama.

PMID- 11843436
TI  - Onset of grip- and pinch-strength impairment after acute poisonings with
      organophosphate insecticides.
AB  - The course of organophosphate-induced delayed polyneuropathy (OPIDP) in humans
      has not been quantitatively measured in epidemiologic studies. This study
      evaluated the association of acute OP poisonings with motor neurologic
      impairment. Hand grip and pinch strength were evaluated among 62 Nicaraguan men
      hospitalized for acute OP poisoning between 1992 and 1996; 39 cattle ranchers and
      fishermen who had never experienced pesticide poisoning were controls. Exposure
      categories were moderate and severe poisonings with neuropathic and non
      neuropathic OPs. Strength was measured at hospital discharge and seven weeks
      after poisoning. Grip and pinch strength were impaired among all OP-poisoned
      subjects at both examinations, more noticeably among those poisoned with OPs with
      suspected neuropathic effects, methamidophos and chlorpyrifos. In those with
      severe poisonings with neuropathic OPs, impairments were more marked among
      intentional than among occupational poisonings. The performances of suicidal
      subjects worsened at the second examination, consistent with OPIDP. Early motor
      impairment at the time of hospital discharge is consistent with cholinergic
      depolarization blockade after acute poisoning. The persistence of deficits in
      motor strength in all severely poisoned patients regardless of pesticide type was
      unexpected, and may reflect persistent cholinergic blockade or intermediate
      syndrome, neuropathy, or a combination of these.

PMID- 11843437
TI  - Long-term neurobehavioral effects of mild poisonings with organophosphate and n
      methyl carbamate pesticides among banana workers.
AB  - Organophosphate poisoning has been associated with chronic neurobehavioral
      dysfunction, but no epidemiologic data exist with regard to long-term
      consequences from carbamate poisoning. This cross-sectional study evaluated the
      neurobehavioral performances of 81 banana workers who, on average 27 months
      earlier, had received medical attention not requiring hospitalization for mild
      occupational poisoning by either an organophosphate or a carbamate pesticide.
      These performances were compared with those of 130 banana workers who had never
      sought medical attention for pesticide poisoning. Poisoned subjects did less well
      than controls on tests measuring psychomotor and visuomotor skills, language
      function, and affect, the differences being significant for coding skills on the
      Digit-Symbol test and two tests of neuropsychiatric symptoms. These deficits, in
      particular a marked increase of neuropsychiatric symptoms, occurred among the
      organophosphate-poisoned subjects, but small deficits in performance were also
      seen in the carbamate-poisoned subjects. The performances of the previously
      poisoned subjects who had had contact with cholinesterase inhibitors within three
      months before testing were particularly poor. These findings in workers with mild
      poisoning are consistent with previous findings of persistent damage to the
      central nervous system from organophosphate poisoning. The possibility of
      persistent neurobehavioral effects associated with poisonings by nmethyl
      carbamate insecticides cannot be excluded. Workers with histories of poisoning
      may be more susceptible to neurobehavioral effects with subsequent exposures.

PMID- 11843438
TI  - Effects of pesticide applications on respiratory health of Ethiopian farm
      workers.
AB  - The effects of pesticide use on the respiratory health of agricultural farm
      workers were studied in 203 farm workers and 131 controls. The farm workers were
      sprayers, supervisors, technicians, and pest assessors. Pulmonary function was
      found to be remarkably poor among the non-smoker supervisors, followed by the non
      smoker sprayers, as compared with that of the non-smoker controls. The means (SD)
      of FVC and FEV1 for supervisors and sprayers were 2.88 (0.41), 3.05(0.50) and
      2.74(0.38), 2.89(0.54), respectively, p < 0.05. The non-smoker technicians had
      the most respiratory symptoms, with wheezing and breathlessness being the most
      frequent (35.7% in 14 technicians). Farm workers with various job experiences are
      subject to reduction of pulmonary function and frequent complaints of respiratory
      symptoms that could possibly lead to chronic respiratory health problems.

PMID- 11843439
TI  - Pesticide-related symptoms among farm workers in rural Honduras.
AB  - A survey of 96 families in a rural region of Honduras, conducted in 1998, showed
      that 80 of these predominantly (95 or 96) farming families used pesticides in
      their work or at home. Paraquat was used most often, and safety measures were
      very rarely taken in its use. Seventy-seven families stored pesticide containers
      in their homes, often within the reach of children. Every worker who used
      paraquat had at least one symptom potentially related to its use, and the
      prevalences of childhood disorders in the region are abnormally high compared
      with national averages.

PMID- 11843440
TI  - Pesticide usage and health consequences for women in developing countries: out of
      sight, out of mind?
AB  - Pesticide exposures of women in developing countries are aggravated by economic
      policy changes associated with structural adjustment programs and globalization.
      Women in these countries, particularly in the agricultural sector, are
      increasingly exposed. Since they are concentrated in the most marginal positions
      in the formal and informal workforces, and production is organized in a gender
      specific way, opportunities for women to control their exposures are limited.
      Data from developing countries show that: 1) women's exposures to pesticides are
      significantly higher than is recognized; 2) poisonings and other pesticide
      related injuries are greatly underestimated for women; 3) for a given adverse
      outcome from exposure, the experience of that outcome is gender-discriminatory;
      4) erroneous risk perception increases women's exposures. The hiatus in knowledge
      of gender-specific exposures and effects is related to gender biases in the
      nature of epidemiologic inquiry and in the literature, and the gendered nature of
      health workers' practices and surveillance. Recommendations are made for strong,
      independent organizations that provide opportunities for women to control their
      environments, and the factors affecting their health, as well as gender-sensitive
      research to address the particularities of women's pesticide exposures.

PMID- 11843441
TI  - International impacts of pesticides on children.
AB  - Pesticide exposures among children fall into a range of regulatory concerns. A
      survey encompassing children's exposures in rural farming communities in Honduras
      illustrates the complexity and magnitude of the problem. Further study and
      international guidelines for prevention are recommended.

PMID- 11843442
TI  - Ames, pesticides, and cancer revisited.
AB  - The case for continuing use of existing levels of pesticides in agriculture,
      espoused by Bruce Ames, is refuted. Ames' contentions that naturally occurring
      carcinogens are far more widespread than man-made ones, that pesticides prevent
      cancer by providing fruits and vegetables at lower costs to the poor, and that
      animal data on high risks with high doses cannot predict low risks from low doses
      in humans do not address key issues: 1) fruits and vegetables contain mixtures of
      carcinogens and anti-carcinogens, and selection effects from human exposures to
      these mixtures go back more than a million years; 2) exposures from
      bioconcentrations of biopersistent organochlorines in the food chain create
      particular risks for meat-eaters, who have higher cancer risks than vegetarians;
      3) even low doses from ingestion of produce containing pesticide residues can
      cause tissue injury, which could itself promote cancer; 4) epidemiologic data
      show rises in cancer incidences in older people in many countries, major
      differences in cancer risks between countries, and converging trends in risks for
      populations migrating to certain countries; 5) studies of pesticide-exposed
      workers consistently show increased rates of cancers and birth defects and
      cancers in their offspring; 6) epidemiologic studies based on large databases
      tend to underestimate risks from environmental causes because of exposure
      misclassification; 7) exposures to many organochlorines may have pervasive
      effects on endocrine function; 8) crop yields can be increased with less use of
      pesticides. Studies demonstrating the latter need replication, and should be
      supported as part of a coherent government agenda to develop alternative farming
      methods.

PMID- 11843443
TI  - Carcinogenicity of pesticides: is everything under control?

PMID- 11843444
TI  - Prosthodontics 21: toward a new era?

PMID- 11843445
TI  - Fracture resistance of all-ceramic and metal-ceramic inlays.
AB  - PURPOSE: Metal-ceramic inlay designs were developed to determine if the esthetic
      qualities of all-ceramic inlays could be duplicated and at the same time improve
      their strength and stability. The objectives of this study were to: (1) compare
      the fracture resistance of metal-ceramic inlays with that of all-ceramic inlays;
      (2) determine the correlation between the degree of preparation taper and
      fracture resistance; and (3) determine the correlation between marginal gap width
      and fracture resistance. MATERIALS AND METHODS: Inlay preparations were made on
      60 Dentoform teeth, with 30 teeth allocated for metal-ceramic inlays and 30 teeth
      for all-ceramic inlays. Each group was further subdivided into 5-, 10-, and 20
      degree taper preparations. Metal-ceramic inlays were fabricated using Goldtech
      Bio 2000 metal and Ceramco porcelain extending to the margin, while all-ceramic
      inlays were made from Empress II ceramic. Marginal gap widths were measured at
      six critical areas after fabrication. The load at failure was measured using an
      Instron Universal Testing Machine. RESULTS: The mean fracture load for all
      ceramic inlays and metal-ceramic inlays at 5, 10, and 20 degrees was 70+/-40 N,
      48+/-37 N, 33+/-7 N, and 40+/-23 N, 29+/-22 N, and 14+/-4 N, respectively. The
      mean gap width was 105 microm and 126 microm for all-ceramic and metal-ceramic
      inlays, respectively. CONCLUSION: The mean fracture load for Empress inlays was
      significantly higher than that for metal-ceramic inlays. Inlays with a 5-degree
      taper were significantly more fracture resistant than those with a 20-degree
      taper. There was no relation between marginal gap width and fracture resistance.

PMID- 11843446
TI  - A finite element stress analysis of the transmandibular implant system.
AB  - PURPOSE: The aim of this work was a simulation of the onset of osseointegration
      of the transmandibular implant system in the mandible. This was achieved by
      imposing joint elements at the implant-bone interface. MATERIALS AND METHODS: The
      geometric model was derived from the anatomic measurement of several mandibles by
      tomographic scanning. The spring constants of the joint elements interposed at
      the implant-bone interface were varied between 1 N/mm and 10(9) N/mm to represent
      the conditions leading to osseointegration. RESULTS: Increasing the value of the
      spring constant at the joint elements gradually increases the effective stress in
      an increasing volume of crestal cortical bone. Additionally, a larger volume of
      crestal cortical bone assumes a higher stress value as the simulation proceeds.
      CONCLUSION: This work indicates that considerable changes in stress magnitude and
      distribution occur in the crestal cortical bone margins as osseointegration is
      simulated, which may be the necessary stimulus for bone remodeling.

PMID- 11843447
TI  - The prevalence of radiologic TMJ findings and self-reported orofacial pain in a
      patient group wearing implant dentures.
AB  - PURPOSE: This study had a twofold aim: first, to gather knowledge about the
      prevalence of radiologic signs of temporomandibular joint osteoarthritis (TMJ-OA)
      and possible risk factors in patients who had worn an implant prosthesis for
      between 2.5 and 10 years; and second, to investigate the diagnostic value of
      radiologic TMJ-OA signs for orofacial pain in a non-temporomandibular disorders
      group. MATERIALS AND METHODS: Two hundred thirty patients (134 women, 96 men)
      answered a questionnaire regarding orofacial pain. In mean, they were 64 years
      old and wore 98 fixed and 132 removable implant dentures. The effect of age,
      gender, state of the dentition, time span after prosthesis placement,
      parafunction, and TMJ sounds on radiologic TMJ-OA signs was estimated through
      multiple logistic regression. The predictive values were calculated to assess the
      diagnostic value of severe TMJ-OA signs to predict orofacial pain. RESULTS:
      Prevalence of TMJ-OA signs was 70% for flattening, 23% for osteophytes, and 24%
      for erosion. Some effect on radiologic TMJ-OA signs of gender and state of the
      dentition was found. The predictive values for orofacial pain from radiologic TMJ
      OA ranged from 0.22 to 0.81. CONCLUSION: Radiologic signs of TMJ-OA were common
      findings. The study gave no indication that long-term wearing of an implant
      prosthesis has a negative effect on TMJ-OA. It was not possible to predict
      orofacial pain from radiologic TMJ-OA signs.

PMID- 11843448
TI  - Effect of acidulated phosphate fluoride solution on veneering particulate filler
      composite.
AB  - PURPOSE: The objective of the current study was to investigate the surface
      morphologic characteristics of prosthodontic composite materials treated with an
      acidulated phosphate fluoride (APF) agent. MATERIALS AND METHODS: Seven composite
      materials (Artglass, Axis, Belleglass, Cesead II, Dentacolor, Solidex, and
      Targis) were examined. Each material was packed into a split plastic mold and was
      polymerized with a laboratory photo-curing unit. Half of each composite disk
      surface was coated with a varnish, and the entire surface of the sample was
      treated with an APF agent. After removal of the varnish, surface roughness values
      (Ra) for the treated and untreated (ie, previously varnish coated) sides of all
      specimens were recorded with a surface analyzer and observed with a scanning
      electron microscope. RESULTS: Ra values for Cesead II, Solidex, and Targis showed
      a significant increase as a result of treatment with the APF solution.
      Microphotographs demonstrated that the macroinorganic fillers in the Cesead II
      and Solidex materials showed substantial dissolution caused by the APF agent.
      There were no significant statistical differences in the Ra values between the
      treated and untreated halves for any of the materials containing inorganic
      fillers composed entirely of diameters up to 1.0 microm. In particular,
      microphotographs of prepolymerized silica composite (classified as microfilled
      materials in Axis and Dentacolor) did not reveal any change of the specimen
      surfaces. CONCLUSION: The APF agent attacked inorganic fillers in the composite
      materials. Microfilled material surfaces were insensitive to the agent in
      comparison with macroinorganic filled material surfaces.

PMID- 11843449
TI  - Effectiveness of maxillary overdentures supported by implants: maintenance and
      prosthetic complications.
AB  - PURPOSE: The aim of this study was to evaluate the prosthetic complications with
      implant-supported overdentures in the maxilla. MATERIALS AND METHODS: Forty-one
      patients (mean age 61 years) were consecutively admitted for treatment from 1991
      to 1998. A total of 173 ITI implants were placed. Four to six implants either
      connected with a bar (34 overdentures) or with single anchors (seven
      overdentures) supported the denture, and only a few parties had fewer than four
      implants. The overdentures had a horseshoe design and were reinforced by a cast
      metal framework. The mean observation time was 3.2 years. Oral hygiene and
      periimplant parameters were regularly assessed, and records were kept of
      prosthetic maintenance service. All prosthetic complications encountered were
      classified related to (1) implant components and anchorage devices, (2)
      mechanical and structural failures of dentures, or (3) denture-related
      adjustments. RESULTS: Three implants did not osseointegrate, and five implants
      were lost after loading. Thus, the overall survival rate of the implants was
      95.5%. Altogether, 85 prosthetic complications were encountered. The most
      frequent finding was retightening of the bar screw and adjustments of the bar
      retainers. Repair of dentures was not frequent and was mostly related to broken
      teeth. No fracture of dentures was observed. Renewal of dentures occurred twice,
      once after loss of all implants in one patient. Thirty-nine overdentures had been
      continuously worn; thus, the overall denture stability was 95%. Mucosal
      irritation and need for occlusal adjustment were the most frequent findings in
      the first year. Over time, a decrease of complications was observed. CONCLUSION:
      Planned maxillary overdentures supported by implants are a successful treatment
      modality on a short-term basis.

PMID- 11843450
TI  - Fracture resistance and primary failure mode of endodontically treated teeth
      restored with a carbon fiber-reinforced resin post system in vitro.
AB  - PURPOSE: This study was undertaken to characterize the fracture resistance and
      mode of fracture of endodontically treated incisors restored with cast post-and
      core, prefabricated stainless steel post, or carbon fiber-reinforced composite
      post systems. MATERIALS AND METHODS: Ten endodontically treated teeth restored
      with each technique were subjected to a compressive load delivered at a 130
      degree angle to the long axis until the first sign of failure was noted. The
      fracture load and the mode of fracture were recorded. RESULTS: The failure loads
      registered in the three groups were not significantly different. Between 70%, and
      80% of teeth from any of the three groups displayed fractures that were located
      above the simulated bone level. CONCLUSION: The use of carbon fiber-reinforced
      composite posts did not change the fracture resistance or the failure mode of
      endodontically treated central incisors compared to the use of metallic posts.

PMID- 11843451
TI  - Accuracy of mechanical digitizing with a CAD/CAM system for fixed restorations.
AB  - PURPOSE: Most research on the accuracy of dental computer-aided
      design/manufacturing (CAD/CAM) systems focuses on the marginal gap. A detailed
      analysis of the various components of CAD/CAM systems (digitizer, software, and
      milling machine) using this approach is nearly impossible. The purpose of this
      study was to determine the accuracy of the manual mechanical digitizer of the
      Precident-DCS system. MATERIALS AND METHODS: Gauge blocks were aligned to the
      coordinate planes of the digitizer to determine the point and length measurement
      uncertainty. The values for each measuring point were compared for statistical
      differences concerning first versus second operator, pressure, and mode of
      sensing using analysis of variance. The measurement uncertainty was given by 95th
      percentiles. RESULTS: The mean one-dimensional point measurement uncertainty in
      the Y direction was 11 microm for the first, 8 microm for the second, and 37
      microm for both operators. The three-dimensional point measurement uncertainty in
      the Y direction was 10 microm for the first, 33 microm for the second, and 60
      microm for both operators. The point measurement uncertainty was significantly
      influenced by the pressure during sensing and by the operator as well. There were
      significant differences between the first and second recordings. The length
      measurement uncertainty in the Y direction for a gauge block of 20 mm was 52
      microm for both operators. CONCLUSION: The reliability of the manually guided
      Precident-DCS digitizer is limited because of the significant influence of the
      operator and the mode of sensing (one or three dimensional). Compared with an
      automatic digitizing system, the measurement uncertainty of the manually guided
      digitizer exceeds the values published in the literature.

PMID- 11843452
TI  - A laboratory investigation of the accuracy of two impression techniques for
      single-tooth implants.
AB  - PURPOSE: This laboratory study investigated the accuracy of four implant
      impression procedures using two impression techniques and two different
      materials. MATERIALS AND METHODS: A master model was used to produce 40 different
      stone casts incorporating laboratory implant or abutment analogues from the
      different combinations of two impression techniques (the repositioning impression
      coping technique at the implant level and the pickup impression technique at the
      abutment level) and materials (President polyvinyl siloxane and Impregum F
      polyether). Variations in the resulting working casts were measured using the
      Reflex Microscope to derive distances and angles from the three-dimensional
      coordinates of optical targets that were attached to a test coping placed on the
      implant analogue and on a reference device positioned on the occlusal surfaces of
      the casts. RESULTS: The results showed greater variations in analogue position
      with the repositioning impression technique than with the pickup technique. The
      rotational errors were large enough to be of clinical concern. No significant
      differences were found between polyvinyl siloxane and polyether impression
      materials for the two tested types of impression techniques. CONCLUSION: The
      repositioning impression technique at the implant level can produce less
      predictable results than the pickup technique at the abutment level. The choice
      of impression material made no significant difference.

PMID- 11843454
TI  - Periodontal considerations in removable partial denture treatment: a review of
      the literature.
AB  - PURPOSE: A critical review of the literature on the periodontal considerations in
      removable partial denture (RPD) treatment is presented. MATERIALS AND METHODS: A
      MEDLINE search was conducted for studies pertaining to the effects of RPDs on the
      periodontal tissues during the various phases of prosthetic treatment. The review
      included both in vivo and in vitro studies. RESULTS: The use of RPDs leads to
      detrimental qualitative and quantitative changes in plaque. There seems to be a
      lack of information regarding the effects of RPDs on the status of periodontally
      compromised abutments. A number of studies, mainly in vitro, have failed to agree
      on the ideal RPD design. Clinical trials have shown that if basic principles of
      RPD design are followed (rigid major connectors, simple design, proper base
      adaptation), periodontal health of the remaining dentition can be maintained.
      CONCLUSION: Removable partial dentures do not cause any adverse periodontal
      reactions, provided that preprosthetic periodontal health has been established
      and maintained with meticulous oral hygiene. Frequent hygiene recalls and
      prosthetic maintenance are essential tools to achieve a good long-term prognosis.
      More prospective clinical trials are needed on the effect of RPDs on the
      condition of periodontally involved abutment teeth.

PMID- 11843453
TI  - A 1-year clinical report of a one-piece implant abutment.
AB  - PURPOSE: Solid one-piece standard and conical abutments, which do not involve the
      external implant hex when seated, have been designed. The present clinical study
      represents a 1-year follow-up of the use of these abutments for anchorage of
      implant-supported fixed prostheses for oral rehabilitation of 36 completely and
      eight partially edentulous patients. MATERIALS AND METHODS: After 1 year of
      loading, the implant-supported dentures were removed, and the seating of the 214
      one-piece abutments was inspected clinically and radiographically. RESULTS: After
      1 year of loading, no loose abutments were observed. One complication was
      reported; it involved fracture of two abutment screws within the same fixed
      denture. Prosthesis mobility and gold screw loosening accompanied this
      complication. Ninety-one percent of the patients exhibited healthy gingiva, and
      9% showed erythema/edema. No periimplantitis was identified. CONCLUSION: The
      results of this study--healthy marginal tissue, a mean bone loss of 0.3+/-0.6 mm,
      and no abutment retightening 1 year after loading--support the use of the one
      piece abutment design in implant-supported screw-retained restorations.

PMID- 11843455
TI  - A study of the use of photographs for denture tooth selection.
AB  - PURPOSE: The aim was to examine a method described by Wehner et al for
      calculating the width of a missing central incisor using preextraction
      photographs. MATERIALS AND METHODS: Three photographic views were obtained for
      each of 30 dentate subjects: full face, oblique, and reduced-size full face. The
      width of the maxillary right central incisor (MR1) was calculated using a
      formula. The difference between the actual width and calculated width of MR1 was
      determined for each subject. The median difference and interquartile range were
      determined because the data were skewed. RESULTS: The width of MR1 calculated
      using the larger full-face view was typically smaller than the actual width, with
      a median difference of -0.18 mm. The interquartile range of the difference was
      from -0.42 to 0.05 mm. For both the oblique and reduced-size views, the
      calculated width was typically larger, with a median difference of 1.19 mm with
      an interquartile range from 0.82 to 1.76 mm and a median difference of 0.84 mm
      with an interquartile range from 0.59 to 1.41 mm, respectively. CONCLUSION: The
      technique described by Wehner et al is of proven value in calculating the width
      of a central incisor when the only available evidence is a preextraction
      photograph. However, it is of value only when the photograph is a full-face
      portrait of sufficient size.

PMID- 11843456
TI  - A pivoting appliance for intracavitary brachytherapy in patients with reduced
      mouth opening.
AB  - PURPOSE: The risks of radiotherapy to normal tissues are well known. In many
      cases, a tumor patient suffering a relapse cannot undergo radiotherapy a second
      time. One exception may be the local application of brachytherapy. Afterloading
      devices allow the position of radiating materials near the site for treatment
      exactly according to three-dimensional treatment planning. This report shows the
      technical procedure for the fabrication of an intracavitary afterloading
      radiation device. MATERIALS AND METHODS: A 48-year-old woman who had received
      neutron radiotherapy and tumor surgery for adenoid cystic carcinoma had to be
      treated for relapse. The mouth opening was limited to 15 mm. The mixing tip of a
      silicone impression system was used as an axis for a pivoting appliance. RESULTS:
      Two years after reradiation, the patient was free of relapse symptoms, although
      an increased limitation of mouth opening was recorded. CONCLUSION: Even if the
      mouth opening is severely limited after tumor surgery and/or radiation,
      intracavitary brachytherapy still can be performed in edentulous patients using a
      pivoting device.

PMID- 11843458
TI  - Geographic differences in implantable cardioverter defibrillator usage.
AB  - Despite the demonstrated efficacy of implantable cardioverter defibrillators
      (ICDs) in reducing sudden and total mortality in selected patients, their
      implantation rates vary greatly among countries. In the United States, the
      implantation rate is 185 implants per million inhabitants compared with only 31
      implants per million in western Europe. The differences in ICD use may be
      explained by the following factors: manner in which sudden cardiac death is
      perceived by politicians and physicians (sudden cardiac death is perceived as a
      "nice way of dying"); differences in indications; physicians' information;
      prevalence of coronary artery disease; sudden cardiac death survival rates;
      perceived reliability of alternative treatment (namely, antiarrhythmics including
      amiodarone); economic backgrounds; and health care politics. Furthermore, the
      cost of this treatment strategy must be considered. This issue has been raised
      because generalization of ICD use in patients matching clinical characteristics
      of patients enrolled in the primary prevention trials may represent a significant
      economic burden to be added to the already overloaded health care system. This
      low acceptance may not be entirely related to budget constraint but also to the
      perceived efficacy of ICDs by physicians and health authorities.

PMID- 11843457
TI  - A 3-year prospective study of a single-tooth implant--prosthodontic
      complications.
AB  - PURPOSE: The objective of this 3-year prospective study was to evaluate a new
      titanium dental implant system and to identify any mechanical concerns or
      deficiencies in its design. MATERIALS AND METHODS: One periodontist placed 78
      single-tooth implants in 59 subjects. One restorative dentist using one dental
      laboratory fabricated all of the crowns. Each patient then was seen eight times
      by the authors for clinical, radiographic, and laboratory testing. RESULTS: One
      of the 78 implants failed to integrate and was removed. There were no structural
      failures per se, although six of the cemented crowns and six of the restorative
      posts and cores (abutments) became loose. On a few occasions, the emergence
      profile was esthetically or functionally unsatisfactory. The manufacturer
      introduced changes in design and created an adjustable torque wrench, a torque
      adjusting beam scale, and die replicas of the abutment posts in response to the
      identified concerns. CONCLUSION: The clinical trial helped in the development of
      an implant system that is user friendly, cost effective, and able to withstand
      parafunctional forces in the absence of antirotational features.

PMID- 11843459
TI  - Role of implantable cardioverter defibrillators in dilated cardiomyopathy.
AB  - Idiopathic dilated cardiomyopathy (DCM) accounts for about 10,000 deaths per year
      in western countries. Of these deaths, 8% to 51% occur suddenly, with more than
      half of the events due to a ventricular arrhythmia. Improvement in diagnostic
      techniques and therapeutic strategies, together with changes in secular trends,
      have likely contributed to the reported trend toward improved survival in recent
      years. Identification of DCM patients at higher risk of sudden death is
      difficult. Poor left ventricular function is the strongest predictor of all-cause
      death, whereas a history of sustained unstable ventricular arrhythmia or cardiac
      arrest identifies patients at high risk of sudden death. Recent data suggest that
      a history of syncope, regardless of inducibility at programmed electrical
      stimulation, may be a risk factor of sudden death. Despite the absence of
      controlled studies, use of implantable cardioverter defibrillator therapy for
      primary prevention can be considered in patients with unexplained syncope as well
      as subgroups of DCM patients awaiting transplantation. In patients who survive a
      cardiac arrest or an unstable ventricular tachycardia, use of implantable
      cardioverter defibrillator therapy is associated with improved survival during
      follow-up and should be considered as a first-line therapy.

PMID- 11843460
TI  - Cost-effectiveness of implantable cardioverter defibrillator therapy.
AB  - Cost-efficacy assessment of implantable cardioverter defibrillator (ICD) therapy
      has proved contentious and may have limited uptake of ICD therapy, particularly
      in Europe. Published modeling assessments are too inaccurate to determine
      clinical practice, and assessments based on clinical studies are incomplete (from
      the cost-efficacy viewpoint). Although ICD therapy seems certain to be most cost
      effective in patients who are likely to have good longevity if their risk of
      sudden cardiac death is countered, the benefit of ICD therapy is not necessarily
      limited to such groups. Physicians and health economists need to develop a better
      understanding of how to assess high-technology therapy costs so that uptake of
      such therapy is appropriately expedited with due regard to ethical and cost
      constraints.

PMID- 11843461
TI  - How and when to pace in vasovagal syncope.
AB  - This article discusses the indications for pacing in vasovagal syncope. It also
      reviews the literature on pacing results; notably, there are two small randomized
      controlled trials of pacing versus no therapy (or continued nondevice therapy)
      that show a clear benefit for pacing. The mode of benefit is, as yet, unclear.
      Pacing has to be dual chamber with some form of rate hysteresis. Ways of
      improving pacemaker therapy delivery in vasovagal syncope are anticipated.

PMID- 11843462
TI  - We have come a long way with device therapy: historical perspectives on
      antiarrhythmic electrotherapy.
AB  - The history of device therapies 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 BC, Wang Shu He wrote 10 books about the pulse. The
      Greeks called the pulse "sphygmos"; thus, sphygmology 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 growing clinical importance of electrical
      cardiac stimulation was recognized and renewed as Zoll in 1952 described a
      successful resuscitation in cardiac standstill by external stimulation.
      Meanwhile, millions of patients with cardiac arrhythmias worldwide have been
      treated with pacemakers in the last 40 years. The concept of a fully automatic
      implantable cardioverter defibrillator system 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 involved atrial and atrioventricular defibrillators, radiofrequency
      ablation, laser therapy, and advanced antiarrhythmic surgery. Since 1990, there
      has been a growing interest in using cardiac pacing as additional treatment in
      severe cardiac failure. Recent reports have suggested that intervention with left
      ventricular or biventricular pacing may be helpful for a subgroup of patients
      with congestive heart failure. Despite encouraging (preliminary) acute and short
      term results, pacing strategies for heart failure still are limited and currently
      regarded as investigational. Advances in the field of therapeutic application of
      pharmacologic and electrical tools as well as alternative methods will continue
      as rapidly as before and provide us further significant aid in taking care of
      patients.

PMID- 11843463
TI  - Geographic differences of pacemaker implant rates in Europe.
AB  - INTRODUCTION: Pacemaker therapy, which has proved to be the only treatment for
      symptomatic bradyarrhythmias, exhibits great variation from country to country
      around the world. The aim of this study was to examine the variations in the
      number of first implants per calendar year in different European countries and to
      relate the differences to certain socioeconomic indices. METHODS AND RESULTS:
      Information concerning new pacemaker implants during the year 1999 was obtained
      from the European Pacemaker Registry, which is maintained by the Working Group of
      Cardiac Pacing of the European Society of Cardiology. Comparisons of pacemaker
      and econometric indices between western and eastern Europe were carried out using
      the t-test. Correlations between selected pacemaker parameters and econometric
      indices were examined using univariate and multivariate regression analysis. Our
      findings reveal significant geographic differences in both the number of first
      implants and the types of pacemaker implanted. The gross domestic product is
      strongly related to the number of new pacemaker implants per year, as well as the
      number of pacing centers in individual countries. CONCLUSION: Significant
      geographic variations exist within Europe as to the number of annual pacemaker
      implants and the types of pacemakers implanted. These variations are related to
      specific economic indices in the countries concerned.

PMID- 11843464
TI  - Relevance of atrial fibrillation classification in clinical practice.
AB  - Use of different classifications for atrial fibrillation reflects the complexity
      of the arrhythmia and the difficulty in grouping its different aspects. Current
      classifications are based on clinical presentation, etiology, substrates,
      mechanisms, etc. From the clinical point of view, the most relevant probably
      should be one directed at classifying patients in terms of therapeutic options.
      In this article, a review of known classifications is given, together with an
      attempt at a new classification based on the possibility of offering a
      nonpharmacologic treatment to patients.

PMID- 11843465
TI  - Suppression of atrial tachyarrhythmias by pacing.
AB  - INTRODUCTION: Treatment of atrial tachyarrhythmias (ATs) remains difficult in
      many patients. Accordingly, new therapeutic approaches for AT suppression are
      evaluated. Atrial pacing may prevent ATs by modifying the electrophysiologic
      conditions required for sustained ATs. METHODS AND RESULTS: New pacing algorithms
      for prevention of AT are aimed at permanent overdrive suppression of arrhythmic
      activity, reduction of dispersion of atrial refractoriness produced by short-long
      cycles, more aggressive overdrive pacing after spontaneous sinus conversion to
      prevent early reinitiation of ATs, and prevention of inadequate rate decay in
      patients with vagally induced ATs. AT prevention may be achieved by dedicated
      atrial pacing sites, e.g., pacing at the insertion of Bachmann's bundle or
      biatrial pacing, which compensates for interatrial conduction delay. Preexciting
      regions of critical conduction delay, pacing at the triangle of Koch or coronary
      sinus os, and dual-site right atrial pacing have shown antiarrhythmic effects.
      Atrial preventive pacing and pharmacologic treatment may work synergistically in
      the concept of hybrid therapy. To prevent atrial electrical remodeling, early
      termination of AT seems desirable. This may be achieved by implanted devices that
      automatically detect ATs and provide atrial antitachycardia pacing for organized
      ATs. Initial studies showed that regular AT can automatically be terminated in
      approximately 50% of treated episodes. CONCLUSION: Pacing for prevention of AT
      and termination of organized AT episodes may become important steps within the
      concept of hybrid therapy of AT. However, their clinical efficacy and optimal
      patient selection remain to be evaluated in prospective, well-designed clinical
      trials.

PMID- 11843466
TI  - "Pills and pulses": hybrid therapy for atrial fibrillation.
AB  - Nonpharmacologic techniques are being increasingly applied to the treatment of
      atrial fibrillation (AF). None of these techniques (other than maze surgery)
      begins to approach 100% efficacy for long-term elimination of arrhythmia. This
      review examines the evidence for "hybrid" therapy, using combinations of drug and
      nonpharmacologic treatments. The immediate success rate of electrical
      cardioversion can be increased with amiodarone or ibutilide, and a number of
      drugs reduce the risk of AF recurrence. Preventing or reversing electrical atrial
      remodeling is an attractive strategy for maintenance of sinus rhythm. However,
      the available evidence (relating to the use of verapamil) is limited and
      conflicting. Ablation of the cavotricuspid isthmus is effective when
      antiarrhythmic drugs given for AF give rise to typical flutter. Isthmus and other
      right atrial linear lesions are poor as a sole therapy for AF, but better when
      drugs are added. Better still is the combination of left atrial linear lesions
      with drugs. In patients with AF recurrence following focal ablation/pulmonary
      vein isolation procedures, drugs are an alternative to extensive linear ablation.
      Some studies indicate that pacing to prevent AF may be effective, but rarely
      without continued antiarrhythmic drug therapy. This may represent a specific
      effect or simply improved drug tolerance. Drugs also might assist pacemaker
      therapy by increasing the proportion of atrial arrhythmias that are highly
      organized and thus amenable to antitachycardia pacing. This and other forms of
      hybrid therapy will remain the subject of conjecture in the absence of controlled
      clinical trials, which are urgently needed.

PMID- 11843467
TI  - Selection of endpoints in atrial fibrillation studies.
AB  - Atrial fibrillation (AF) is the tachyarrhythmia of the new millennium. There has
      been a dramatic increase in research on the management of this problem over the
      last 10 years. Presently, there is no clear consensus on the most appropriate
      endpoints to be used in studies of therapy for AF, particularly those concerning
      rhythm management itself. Endpoints for studies of rhythm management should be
      based firmly on the objectives of therapy for AF. Some objectives of therapy are
      obvious, but others, such as reduction of mortality, are not and are somewhat
      controversial. Clinically relevant endpoints are to be preferred but have been
      underutilized. Using clinical events as endpoints is complicated by the fact that
      event rates are low and large sample sizes are needed. Cost and cost
      effectiveness are endpoints that are becoming increasingly important but also
      have been underutilized. Clinical classification of AF is an important factor to
      be considered in planning studies of AF rhythm management. Patient selection can
      have a profound effect on the outcome of certain surrogate endpoints. The main
      limitation of these endpoints is that they assume improvement in the surrogate
      measurement is closely correlated to a good clinical outcome. In fact, there is
      ample evidence that such a correlation is quite poor at times. Potential
      solutions to the problems discussed here include wider appreciation of the
      problem, use of carefully crafted composite clinical endpoints, and better
      calibration of surrogate endpoints against clinical endpoints. More research on
      these issues is urgently needed.

PMID- 11843468
TI  - Current limitations in treatment of heart failure: new avenues and treatment
      options.
AB  - Chronic heart failure is one of the main causes of death in western countries.
      Despite state-of-the-art treatment including angiotensin-converting enzyme
      inhibitors, beta-blockers, and spironolactone, survival and relief from symptoms
      still are unacceptably poor in patients with chronic heart failure. The present
      article gives an overview of current limitations in the treatment of heart
      failure and points out possible treatment options in the future. It seems
      possible to reduce or at least delay progression of heart failure by adding drugs
      that interfere with novel pathophysiologic aspects in heart failure activation of
      the neuroendocrine system, including catecholamines, angiotensin II, cytokines,
      and endothelins, as well as alteration of calcium homeostasis and energy
      depletion.

PMID- 11843469
TI  - Optimal stimulation of the left ventricle.
AB  - Cardiac resynchronization therapy has been proposed to alleviate heart failure
      symptoms refractory to classic drug treatment. Potential benefits hinge on a
      number of key components, including judicious selection of patients likely to
      respond to the therapy and appropriate placement of the leads, particularly the
      lead responsible for left ventricular pacing. Evidence of ventricular asynchrony
      is an individual prerequisite for consideration of cardiac resynchronization
      therapy. Ventricular asynchrony can be diagnosed by recording a QRS duration >150
      msec or during echocardiography, with the goal of investigating the mechanical
      aspect of asynchrony. The optimal left ventricular pacing site can be defined by
      the latest segmental contraction, which is mainly the mid-lateral wall. The first
      choice technique to initiate left ventricular pacing consists of a transvenous
      approach via the coronary sinus tributaries. In practice, the final left
      ventricular pacing location also depends on highly variant coronary sinus
      anatomy, acceptable electrical parameters, and lead stability. Procedure-related
      complications, which consist mainly of coronary sinus perforation and phrenic
      nerve stimulation, remain low (<1%) and should decrease further with the use of
      new features specific to the procedure.

PMID- 11843470
TI  - Patient selection for biventricular pacing.
AB  - INTRODUCTION: Biventricular pacing improves functional status in the majority of
      patients with drug-refractory heart failure, dilated cardiomyopathy, and
      interventricular conduction delay. The aim of this study was to analyze the
      baseline clinical and functional data of a cohort of patients implanted with a
      biventricular stimulation system in a single-center experience, to verify if the
      pathophysiologic characteristics of patients affect outcome, and to determine if
      preliminary identification of the right candidates for the new therapy is
      possible with noninvasive parameters. METHODS AND RESULTS: Since March 1999, 52
      patients with advanced heart failure (idiopathic cardiomyopathy 50%, ischemic
      cardiomyopathy 35%, other etiology 15%) and left bundle branch block underwent
      cardiac resynchronization and were followed prospectively. Paired analysis over
      mean (+/- SD) follow-up of 348 +/- 154 days showed an overall significant
      decrease of QRS width (baseline 194 +/- 33.2 msec vs follow-up 159.6 +/- 20.1
      msec), New York Heart Association (NYHA) functional class (baseline 3.2 +/- 0.5
      vs follow-up 2.3 +/- 0.5), quality-of-life score (baseline 54 +/- 25 vs follow-up
      25 +/- 16), and increase of maximal VO2 (baseline 12.6 +/- 2.5 mL/kg/min vs
      follow-up 15.0 +/- 3.3 mL/kg/min). There were 80% responders (documented,
      persistent decrease > or = 1 NYHA class) and 20% nonresponders (same NYHA class
      or decline of status; need for heart transplant; death due to progressive pump
      failure). No significant differences in baseline clinical and functional
      variables between the two subgroups were observed. In responders, there was a
      highly significant global improvement of all variables; in nonresponders, no
      parameters changed between baseline and follow-up. CONCLUSION: These data confirm
      the role of biventricular pacing in improving the functional status of the great
      majority of a selected patient population having advanced heart failure and left
      bundle branch block with wide QRS complex. Basal demographic, clinical, and
      functional characteristics are not helpful in preliminary selection of
      responders. Simple evaluation of NYHA class confirms favorable outcome
      (improvement of functional and hemodynamic status).

PMID- 11843471
TI  - Continuous hemodynamic monitoring in heart failure.
AB  - Chronic congestive heart failure is associated with high morbidity and mortality,
      frequent hospital admissions, and high treatment costs. As the prevalence and
      incidence of the disease are increasing, there is a clear need to improve the
      management of heart failure patients. Continuous hemodynamic monitoring with an
      implanted device is technically feasible and safe. It provides reliable
      information on central hemodynamic parameters and allows for analysis of long
      term hemodynamic trends. It has been suggested that continuous hemodynamic
      monitoring might improve the management of patients with chronic heart failure.
      This article describes the technical details of the monitoring system and
      presents possible clinical applications, with a focus on beta-blocker therapy,
      diuretics, and volume management. A case is reported, illustrating how
      hemodynamic long-term trends might add valuable information during up-titration
      of beta-blockers. Future implications of hemodynamic monitoring are discussed.

PMID- 11843472
TI  - How do we diagnose syncope?
AB  - INTRODUCTION: The Eastbourne Syncope Assessment Study aims to increase diagnostic
      yield in unexplained syncope while reducing investigational costs. The initial
      study phase was a retrospective analysis of every presentation to the Eastbourne
      General Hospital (a busy nontertiary center in the United Kingdom serving a
      population of 250,000; 24% are older than 65 years) with syncope for the year
      1998. METHODS AND RESULTS: A total of 1,334 cases with syncopal codes were
      identified. Six hundred sixty patients (mean age 64 years) had actually suffered
      an episode of syncope. Forty percent had recurrent syncope, with a mean of 4.7
      previous episodes. Twenty-nine percent of syncope cases remained undiagnosed.
      Forty-four percent were diagnosed as vasovagal, 12% neurologic, 6% due to an
      arrhythmia, 2% drug related, and 2% due to hemorrhage. Thirteen different types
      of investigation were undertaken, with an overall total of 3,264 investigations
      performed at a cost of Pound Sterling 104,285. Diagnosis was achieved by history
      and examination alone in 61% of cases. Excluding history and examination, the
      most cost-effective diagnostic tools were the 7-day patient-activated recorder (R
      test) and tilt testing (Pound Sterling 260 and Pound Sterling 401 per diagnosis,
      respectively). Investigations also were graded by their relative diagnostic
      power. Hospital admission alone accounted for 67% of the cost of investigating
      syncope. CONCLUSION: In syncope, diagnostic rates can be improved and
      investigational costs reduced by concentrating on the most specific, sensitive,
      and cost-effective investigations and by minimizing hospital stay. Such a
      protocol currently is under investigation at our institution.

PMID- 11843473
TI  - Automatic external defibrillator: key link in the chain of survival.
AB  - INTRODUCTION: Sudden cardiac death is a major health problem. Worldwide success
      of resuscitation from out-of-hospital cardiac arrest is modest, with 5% to 10%
      survival to hospital discharge. METHODS AND RESULTS: In the chain of survival,
      early defibrillation (goal <5 min after collapse) is a major determinant of
      successful outcome of resuscitation. This goal is rarely achieved, but the
      automatic external defibrillator (AED) is a promising tool for lay
      defibrillation. The AED is a safe and effective device with nearly 100% accurate
      detection of ventricular fibrillation and nearly 100% accurate detection of a
      nonshockable rhythm. A large uncontrolled experience suggests improved outcome in
      nontraditional responders such as police. Controlled studies of community
      application of the AED are under way. CONCLUSION: The AED is a promising tool in
      the fight against sudden cardiac death and should be studied and supported by all
      scientists involved, including electrophysiologists.

PMID- 11843474
TI  - Evolution of implantable cardioverter defibrillator indications: comparison of
      guidelines in the United States and Europe.
AB  - INTRODUCTION: The rate of implantation of implantable cardioverter defibrillators
      (ICD) is growing much faster in the United States than in western Europe. Among
      several factors, education and awareness of the problem of sudden cardiac death
      might account for this discrepancy. METHODS AND RESULTS: Guidelines for ICD
      implantation developed in the United States and various European countries are
      compared, including the one recently published by the Working Groups on
      Arrhythmias and Cardiac Pacing of the European Society of Cardiology. Although
      all guidelines fully concur in their recommendations for patients after cardiac
      arrest due to ventricular fibrillation and ventricular tachycardia, small but
      noticeable differences in opinion can be traced for patients with sustained
      ventricular tachycardia or syncope, and for primary prevention. In general,
      European guidelines are more restrictive for the latter indications. Whereas U.S.
      guidelines were quickly updated over the years, this process took much longer in
      Europe, and several countries only recently adopted their first guidelines.
      CONCLUSION: Although different in details, the recent release of ICD guidelines
      in major western European countries will undoubtedly lead to a pronounced
      increase of patients protected by this form of therapy in Europe in the coming
      years.

PMID- 11843475
TI  - Electroanatomic analysis of sinus impulse propagation in normal human atria.
AB  - INTRODUCTION: Better understanding of atrial propagation during sinus rhythm (SR)
      in normal hearts under the most normal physiologic conditions may be propaedeutic
      to pathophysiologic studies of complex atrial arrhythmias. In this study,
      qualitative and quantitative analyses of sinus impulse propagation in both atria
      were performed by electroanatomic mapping in patients with no organic heart
      disease who were undergoing an electrophysiologic procedure. METHODS AND RESULTS:
      Seven patients (5 men and 2 women; age 37 +/- 11 years) undergoing ablation of a
      left-sided accessory pathway were considered. Associated heart disease and
      coexisting atrial arrhythmias were excluded. After obtaining informed consent,
      electroanatomic mapping of both atria was performed during SR using a
      nonfluoroscopic system in the postablation phase. Mapping was accomplished in all
      patients with no complications. Qualitative analysis showed that sinus impulse
      propagation gives a reproducible activation pattern with minor individual
      variations. During interatrial propagation, two breakthroughs (anterior and
      posterior) in the left atrium are observed in the majority of cases. The anterior
      breakthrough, which reflects conduction over Bachmann's bundle, is predominant
      and shows a peculiar "preexcitation-like" endocardial activation pattern.
      Quantitative analysis showed minimal individual variations of propagation time
      intervals. Atria are activated simultaneously for 65% +/- 9% of the duration of
      the atrial systolic time interval. CONCLUSION: In normal humans, electroanatomic
      mapping of SR identifies a typical and reproducible propagation pattern during
      SR. Bachmann's bundle plays the most important role in interatrial propagation.
      Atria are activated simultaneously by sinus impulse for a relevant portion of the
      systolic time interval.

PMID- 11843476
TI  - Electroanatomic analysis of sinus impulse propagation in normal human atria.

PMID- 11843477
TI  - Pulmonary vein isolation: comparison of bipolar and unipolar electrograms at
      successful and unsuccessful ostial ablation sites.
AB  - INTRODUCTION: No prior studies have quantitatively analyzed the characteristics
      of bipolar or unipolar electrograms that may be helpful in identifying successful
      ostial ablation sites in patients with atrial fibrillation undergoing segmental
      pulmonary vein isolation. METHODS AND RESULTS: The characteristics of bipolar and
      unipolar electrograms recorded at 185 successful and 120 unsuccessful ostial
      pulmonary venous ablation sites were analyzed in 21 patients with atrial
      fibrillation. A decapolar Lasso catheter was positioned near the ostia of the
      pulmonary veins, and a conventional ablation catheter was used to deliver
      radiofrequency energy at individual ostial sites where pulmonary vein potentials
      were recorded. With both bipolar and unipolar recordings, the only timing
      parameter that distinguished successful from unsuccessful ostial ablation sites
      was the timing of the electrogram recorded by the ablation catheter relative to
      the earliest pulmonary vein potential recorded by the Lasso catheter. With both
      bipolar and unipolar recordings, electrograms demonstrated a larger amplitude at
      successful than at unsuccessful ablation sites. Unipolar electrograms had a
      steeper intrinsic deflection at successful than at unsuccessful ostial ablation
      sites. The morphologies of the unipolar electrograms recorded by the ablation
      catheter and by the contiguous electrode of the Lasso catheter usually were
      identical. CONCLUSION: In patients undergoing segmental isolation of the
      pulmonary veins, unipolar recordings provide more information than bipolar
      recordings helpful in distinguishing successful from unsuccessful ostial ablation
      sites. Furthermore, unipolar recordings, but not bipolar recordings, allow
      accurate localization of the position of the ablation catheter relative to the
      electrodes of the Lasso catheter.

PMID- 11843478
TI  - Remodeling of sinus node function after catheter ablation of right atrial
      flutter.
AB  - INTRODUCTION: The purpose of this study was to investigate the effect of ablation
      of right atrial flutter upon sinus node function in humans. METHODS AND RESULTS:
      This study enrolled 35 patients. Twenty-four patients (16 men and 8 women; age 68
      +/- 11 years) were referred for ablation of persistent atrial flutter (duration 8
      +/- 11 months). After ablation, there was abnormal sinus node function defined as
      a corrected sinus node recovery time (CSNRT) > or = 550 msec. The control group
      consisted of 11 patients who were undergoing pacemaker implantation for sinus
      node disease but did not have a history of atrial dysrhythmias or ablation.
      Within 24 hours of ablation or pacemaker implantation, baseline maximal CSNRT was
      measured through a permanent pacemaker by AAI pacing at six cycle lengths: 600,
      550, 500, 450, 400, and 350 msec. CSNRT then was measured in the same manner at
      48 hours, 14 days, and 3 months after ablation/pacemaker implantation. P wave
      amplitude and duration, and percent atrial sensing also were assessed at the same
      intervals. For patients undergoing atrial flutter ablation, there was progressive
      temporal recovery of CSNRT (1,204 +/- 671 msec at baseline vs 834 +/- 380 msec at
      3 months; P < 0.001) and a significant increase in the percent atrial sensing and
      P wave amplitude at 3 months compared with baseline (P < 0.001). In control
      subjects, there was no change in the CSNRT, percent atrial pacing, or P wave
      amplitude. CONCLUSION: After ablation of persistent atrial flutter, there is
      temporal recovery of CSNRT and increase in spontaneous atrial activity. These
      findings suggest that atrial flutter induces reversible changes in sinus node
      function.

PMID- 11843479
TI  - Diagnostic performance of a dual-chamber cardioverter defibrillator programmed
      with nominal settings: a European prospective study.
AB  - INTRODUCTION: Despite technologic developments, accurate discrimination of
      ventricular tachyarrhythmia from rapid rhythms of nonventricular origin remains a
      challenge. We sought to examine the sensitivity and specificity of a dual-chamber
      arrhythmia detection algorithm, the PARAD algorithm, incorporated in a dual
      chamber implantable cardioverter defibrillator, the Defender (ELA Medical).
      METHODS AND RESULTS: All detailed tachycardia episodes (i.e., with stored atrial
      and ventricular channel markers and electrograms) retrieved from the Holter
      memory of the device were analyzed from 95 patients (86 men and 9 women; age 62
      +/- 12 years) implanted with the Defender with the algorithm programmed at
      nominal settings. Over a follow-up of 15 +/- 8 months, 559 detailed sustained
      tachycardia episodes detected in the tachycardia zone were gathered in 62
      patients. Of the 300 ventricular tachycardia (VT) episodes, 298 were
      appropriately classified as VT by the algorithm. Of the 259 supraventricular
      tachycardia (SVT) episodes, 231 were appropriately classified as SVT. In 8
      patients, 28 episodes of SVT were misclassified as VT: 25 atrial fibrillation
      episodes (6 patients), 2 sinus tachycardia (1 patient), and 1 atrial tachycardia.
      Calculated sensitivity and specificity were 99.3% and 89.2% on a per episode
      basis and 99.8% (95% confidence interval: 97.8 to 100) and 91.6% (95% confidence
      interval: 86.0 to 97.3) on a per patient basis, respectively. CONCLUSION: In this
      selected population of patients, the PARAD algorithm was safe and reliable for
      detection of a wide spectrum of tachyarrhythmias. Its specificity was high,
      particularly with respect to sinus tachycardia detection, but it must be improved
      with respect to detection of atrial fibrillation.

PMID- 11843480
TI  - Response of pulmonary vein potentials to premature stimulation.
AB  - INTRODUCTION: Pulmonary vein potentials reflect depolarization of muscle
      fascicles within the myocardial sleeves that surround the pulmonary veins. The
      response of pulmonary vein potentials to premature stimulation has not been
      described. METHODS AND RESULTS: In 31 patients with paroxysmal atrial
      fibrillation referred for segmental isolation of the pulmonary veins, programmed
      stimulation with a single atrial extrastimulus was performed from the coronary
      sinus. Bipolar and unipolar electrograms were recorded with a decapolar Lasso
      catheter positioned sequentially within the left superior, left inferior, and
      right superior pulmonary veins, near the ostium. Premature stimulation often
      resulted in greater separation of the atrial and pulmonary vein potentials
      recorded within the pulmonary veins, fractionation of the pulmonary vein
      potentials, a change in the circumferential activation sequence of the pulmonary
      vein potentials, and dropout of pulmonary vein potentials. CONCLUSION: In
      response to premature stimulation, the muscle fascicles within the myocardial
      sleeves that surround the pulmonary veins display a greater degree of decremental
      conduction than do the myocardial fibers in the adjacent left atrium, and they
      display heterogeneity in conduction properties and refractoriness. Discrimination
      of pulmonary vein potentials from atrial electrograms is facilitated by premature
      stimulation.

PMID- 11843481
TI  - Implantable cardioverter defibrillator utilization based on discharge diagnoses
      from Medicare and managed care patients.
AB  - INTRODUCTION: Implantable cardioverter defibrillators (ICDs) have become an
      accepted therapy for patients at high risk of sudden cardiac death. To assess the
      current utilization of this therapy, we estimated the number of patients at risk
      of sudden death using an historical claims-based study and compared these results
      to current ICD usage volumes. METHODS AND RESULTS: Managed care and Medicare
      databases (claims related to 4.6 million covered U.S. lives during a 12-month
      period) were analyzed to identify patients who had either a primary or secondary
      diagnosis of ventricular tachycardia, ventricular fibrillation, ventricular
      flutter, or cardiac arrest. These patients were further required to have a
      diagnosis code indicating a previous myocardial infarction or congestive heart
      failure. Patients who died during the study period or did not have medical
      insurance were excluded. In the base case scenario, 1,226 patients per million
      population were identified as potential ICD candidates. Sensitivity analyses
      reduced that value to a range from 736 to 1,140 ICD candidates per million
      population. Sensitivity factors considered included acute myocardial infarction,
      comorbidities, age, secondary ventricular tachycardia/ventricular fibrillation
      diagnosis, and varying degrees of left ventricular dysfunction. These results
      contrast with an ICD usage rate of 416 per million population in the United
      States and lower rates in other countries. CONCLUSION: This study suggests that,
      based on discharge diagnoses, many patients who could benefit from ICDs are not
      receiving this therapy. Diverse reasons for this underutilization should be
      addressed to improve access to, and appropriate use of, this therapy.

PMID- 11843482
TI  - Accelerated inactivation of voltage-dependent K+ outward current in
      cardiomyocytes from thyroid hormone receptor alpha1-deficient mice.
AB  - INTRODUCTION: Thyroid hormone affects the electrophysiologic properties of the
      heart. It is not known which of the different subtypes of thyroid hormone
      receptors mediate these effects. METHODS AND RESULTS: Using standard patch-clamp
      techniques, we studied time- and voltage-dependent properties of depolarization
      activated K+ currents in ventricular heart cells isolated from mice lacking the
      thyroid hormone receptor alpha1 (TR alpha1) and compared these currents with
      those in respective wild-type cells. In both groups of cells, the time course of
      current decay could be described by two inactivating exponential components and a
      sustained current component. In TR alpha1-deficient cells, the total inactivation
      time course was accelerated due to both increase of the relative contribution of
      the fast component and shortening of the slow time constant. The peak amplitude
      of the total current was not altered. The main component of steady-state
      inactivation of the voltage-dependent K+ outward current was shifted to more
      hyperpolarized voltages by 7 mV in TR alpha1-deficient cells compared with that
      in wild-type cells. Under current-clamp conditions, action potential duration at
      90% repolarization was prolonged in TR alpha1-deficient cells compared with that
      in wild-type cells by 3.6 msec. CONCLUSION: The resulting acceleration of the
      total inactivation time course is proposed to contribute to action potential
      prolongation and thus to the increased QTend-time observed previously on ECG of
      TR alpha1-deficient mice.

PMID- 11843484
TI  - Acute and chronic electrophysiologic changes surrounding radiofrequency lesions.
AB  - INTRODUCTION: Arrhythmia recurrences may occur after acutely successful
      radiofrequency (RF) ablation, suggesting reversible electrophysiologic effects on
      myocardial tissue. The aim of this study was to examine the electrophysiologic
      changes occurring in myocardium surrounding acute and chronic RF lesions. METHODS
      AND RESULTS: RF lesions (60 degrees C for 30 sec) were produced on the epicardial
      left ventricular surface of 35 isolated perfused rabbit hearts. Microelectrode
      transmembrane action potential recordings were made at 0.25-mm intervals along
      the epicardial (n = 20) or intramural (n = 6) aspects of the lesions for up to
      3.5 mm from the lesion edge at baseline and after acute RF lesion formation. In
      nine hearts, chronic lesions were studied with epicardial recordings made 22 +/-
      13 days after RF lesion formation. In the acute hearts at 600-msec paced cycle
      length, action potential duration at 50% repolarization (APD50) and 90%
      repolarization (APD90) were reduced by up to 41% and 19%, respectively, within
      2.5 mm from the lesion edge (all P < 0.05). Maximal action potential amplitude
      (APDmax) was reduced by 16% at 0.25 mm from the lesion edge (P = 0.009) but dV/dt
      was not changed. Conduction time (CT) from the outermost recording site to the
      lesion edge (3.5-mm distance) was reduced from 16 +/- 3 msec at baseline to 13 +/
      4 msec post ablation (P = 0.006). Qualitatively similar findings occurred at 200
      msec cycle lengths. There were no changes in APD, CT, APDmax, or dV/dt
      surrounding the chronic lesions at 22 +/- 13 days after lesion formation.
      CONCLUSION: Acutely following RF energy delivery, APD, APDmax, and CT are reduced
      in the tissue surrounding the lesion. These electrophysiologic changes resolve
      within 22 +/- 13 days of lesion formation.

PMID- 11843483
TI  - T wave alternans as a predictor of spontaneous ventricular tachycardia in a
      canine model of sudden cardiac death.
AB  - INTRODUCTION: We recently developed an ambulatory canine model of spontaneous
      ventricular tachycardia (VT) and sudden cardiac death by creating myocardial
      infarction, complete AV block, and infusion of nerve growth factor to the left
      stellate ganglion. Whether or not T wave alternans is associated with the
      spontaneously occurring episodes of VT in our model was unclear. METHODS AND
      RESULTS: Through intracardiac electrograms obtained from an implantable
      cardioverter defibrillator, we manually measured T wave amplitudes prior to VT
      and while the dogs were at rest (baseline, no VT). Of the 79 VT episodes
      analyzed, 28 (35.4%) exhibited repolarization alternans. In contrast, only 3
      (4.7%) of 64 baseline data cases displayed alternans (P < 0.0001). The magnitude
      of T wave alternans for dogs that died of sudden cardiac death, dogs that did not
      die suddenly, and for the total 28 episodes that exhibited repolarization
      alternans were 4.8 +/- 2.8 mm, 4.9 +/- 3.5 mm, and 4.9 +/- 3.3 mm, respectively
      (P = NS). We also found the sensitivity, specificity, positive predictive value,
      negative predictive value, and relative risk of repolarization alternans in
      predicting VT to be 35.4%, 95.3%, 90.3%, 54.5%, and 1.98, respectively. The
      ventricular rate prior to VT (65 +/- 11 beats/min) was significantly higher than
      that at rest (49 +/- 12 beats/min; P < 0.0001). CONCLUSION: T wave alternans
      often occurred immediately before the onset of VT in dogs with myocardial
      infarction, complete AV block, and nerve growth factor infusion to the left
      stellate ganglion. Increased sympathetic activity might be responsible for the
      occurrence of the T wave alternans.

PMID- 11843485
TI  - Mind the model: effect of instrumentation on inducibility of atrial fibrillation
      in a sheep model.
AB  - INTRODUCTION: Atrial electrical remodeling, shortening of the atrial effective
      refractory period (AERP) underlying atrial fibrillation (AF) has been described
      in different animal models. However, there remains some controversy regarding the
      time course of this electrical remodeling and the need for secondary factors in
      the development of AF. We investigated the effect of instrumentation on the
      inducibility of AF. We hypothesized that epicardial instrumentation could be a
      confounding factor that accelerates the development of AF. METHODS AND RESULTS:
      Thirty sheep were rapidly atrially paced at 600 beats/min for 15 weeks: 15 were
      endocardially instrumented and paced (endo), and 15 were both endocardially and
      epicardially instrumented. Six of these animals were endocardially paced (sham)
      and 9 were epicardially paced (epi). The underlying rhythm was determined at
      regular intervals, and electrophysiologic study was performed. AF developed
      significantly faster in the epi group. After 3 weeks of pacing, the cumulative
      incidence of sustained AF (>1 hour) already was 70% in this group versus only 14%
      and 20% in the endo and sham groups, respectively. After 15 weeks of pacing, this
      difference was no longer evident. Baseline AERP and minimal AERP, reached before
      the development of AF, were not significantly different in the three groups.
      Epicardial instrumentation (epi and sham) increased baseline left and right
      atrial pressures, but only epicardial stimulation (epi) led to early development
      of AF. CONCLUSION: In this sheep model of AF, the experimental setup is a major
      determinant of the inducibility of AF. Not epicardial instrumentation per se but
      epicardial stimulation accelerated the development of AF. Different animal models

PMID- 11843486
TI  - Focal atrial tachycardia originating from the musculature of the coronary sinus.
AB  - Focal atrial tachycardias originate predominantly from the right atrium along the
      crista terminalis and less commonly from the left atrium. Successful catheter
      ablation usually can be performed via an endocardial approach. We report the case
      of a 34-year-old patient in whom a focal atrial tachycardia was successfully
      ablated 4 cm within the coronary sinus after extensive mapping of the left atrial
      endocardium and coronary sinus using the three-dimensional CARTO mapping system.
      Rarely, atrial tachycardia can originate from the coronary sinus musculature and
      require ablation inside the coronary sinus.

PMID- 11843487
TI  - Use of an insertable loop recorder in a myotonic dystrophy patient.
AB  - The case of a 66-year-old woman with myotonic dystrophy is presented. This
      patient underwent implantation of an insertable loop recorder as a participant in
      a clinical trial. At 1-month follow-up, interrogation of the insertable loop
      recorder revealed multiple episodes of wide complex tachycardia. She underwent
      electrophysiologic study, which revealed moderate His-Purkinje disease, focal
      atrial tachycardia, monomorphic ventricular tachycardia, and ventricular
      fibrillation. Successful radiofrequency ablation of the focal atrial tachycardia
      and implantation of a dual-chamber implantable cardioverter defibrillator was
      performed.

PMID- 11843488
TI  - Latent Mahaim fiber as a cause of antidromic reciprocating tachycardia:
      recognition and successful radiofrequency ablation.
AB  - The term "Mahaim fiber" usually is applied to an atriofascicular fiber that
      inserts distally into the right bundle branch and forms the anterograde limb of a
      reciprocating tachycardia. One of the features that has been used to describe the
      physiology of Mahaim fibers is the presence of anterograde preexcitation. We
      describe two patients who had a clinical tachycardia consistent with a "Mahaim
      tachycardia" in whom there was no evidence or minimal evidence of anterograde
      preexcitation during sinus rhythm or atrial pacing. In both patients, the
      tachycardia was rendered noninducible by radiofrequency ablation at the site of
      Mahaim potentials at the tricuspid annulus, and a long-term cure was achieved.
      This is the first description of a "latent Mahaim fiber" that does not cause
      preexcitation but which can support antidromic reciprocating tachycardia.

PMID- 11843489
TI  - Human pathologic validation of left ventricular linear lesion formation guided by
      noncontact mapping.
AB  - This case report describes the histopathologic findings associated with two left
      ventricular, linear radiofrequency lesions in a patient who underwent cardiac
      transplantation shortly after an ablation procedure for ventricular tachycardia.
      The lesions were created with conventional ablation equipment guided by a
      noncontact mapping system. The findings provide pathologic validation that
      continuous, linear lesions are feasible using a noncontact mapping system for
      guidance.

PMID- 11843490
TI  - Interaction between the autonomic nervous system and atrial tachyarrhythmias.
AB  - Atrial tachyarrhythmias are the most common arrhythmias in the general
      population. The abundant experimental evidence suggests that the autonomic
      nervous system plays an important role in the occurrence of atrial arrhythmias.
      However, complex interactions of the autonomic nervous system with the
      arrhythmogenic substrate make it difficult to correlate human arrhythmias with
      the laboratory data. Development of new methods to explore the subtle modulation
      of the autonomic nervous system may have implications for understanding the
      arrhythmogenic mechanism and providing an effective therapy.

PMID- 11843492
TI  - QRS and cycle length alternans during paroxysmal supraventricular tachycardia:
      what is the mechanism?

PMID- 11843491
TI  - Calcium cycling in heart failure: the arrhythmia connection.
AB  - Ventricular tachycardia in nonischemic heart failure (HF) arises from a
      nonreentrant mechanism most likely due to delayed afterdepolarizations from
      activation of a transient inward current (I(ti)). We present data and a paradigm
      in which an up-regulated Na/Ca exchanger, residual beta-adrenergic
      responsiveness, and decreased inward rectifying K current (I(K1)) in HF all
      conspire to markedly increase the propensity for triggered arrhythmias. The up
      regulated Na/Ca exchanger plays an additional critical role in unloading the
      sarcoplasmic reticulum of Ca, thereby causing the mechanical dysfunction. It is
      imperative that therapeutic approaches for ventricular tachycardia in HF take
      into consideration cellular Ca handling and excitation-contractile coupling, and
      their alteration in the failing heart.

PMID- 11843493
TI  - "Twiddler syndrome" in a subpectorally implanted cardioverter defibrillator.

PMID- 11843494
TI  - Imaging of the atrioventricular node using optical coherence tomography.

PMID- 11843495
TI  - Mechanisms of cavitation and the formation of stable bubbles on the Bjork-Shiley
      Monostrut prosthetic heart valve.
AB  - BACKGROUND AND AIMS OF THE STUDY: Transcranial Doppler studies performed on
      patients with the Bjork-Shiley Monostrut mechanical heart valve have detected
      signals typical of gaseous emboli. METHODS: In this study, a high-speed digital
      imaging system was used to examine the closure event of the Bjork-Shiley
      Monostrut valve in vitro. RESULTS: Observations support the hypothesis that
      cavitation occurs before the formation of stable gas bubbles. Bubble cavitation
      occurs at the instant of valve closure and lasts on the order of 0.3 ms. The
      rebounding motion of the occluder initiates the development of a vortex which
      induces vortex cavitation. Vortex cavitation begins approximately 0.5 ms after
      impact of the occluder and the valve housing (approximately 0.2 ms after bubble
      cavitation has subsided), and lasts for approximately 1 ms. The formation of
      stable bubbles occurs later, along the center of the vortex that persists
      throughout much of the first rebound. CONCLUSION: It is hypothesized that the low
      pressure region at the center of the vortex contributes to the formation of
      stable bubbles by collecting expanded nuclei that arise from both bubble and
      vortex cavitation, and providing a low-pressure environment in which the nuclei
      combine and continue to grow.

PMID- 11843496
TI  - Three-dimensional imaging of fractures in outlet struts of Bjork-Shiley convexo
      concave heart valves by microcomputed tomography in vitro.
AB  - BACKGROUND AND AIMS OF THE STUDY: For implanted Bjork-Shiley convexo-concave
      (BSCC) heart valves, structural failure of the valve's U-shaped outlet strut
      results in embolization of its blood flow-regulating disc (occluder), with
      consequent patient morbidity and mortality. After a variable and unpredictable
      number of cardiac cycles, one strut leg may fatigue ('single-leg separation';
      SLS); subsequently the other strut leg may also fatigue, resulting in full
      structural failure ('outlet strut failure'; OSF). Some BSCC valves are believed
      to be at more risk of SLS and OSF than others. As valves may function in the SLS
      condition for some time before OSF occurs, several investigators have sought non
      invasive methods to differentiate valves with SLS struts from valves with intact
      struts in order to provide a rationale for prophylaxis. Herein, we report the use
      of X-ray microcomputed tomography (micro-CT) to image and characterize SLS strut
      fractures, including fracture faces otherwise visible only by means of physical
      sectioning. METHODS: An X-ray micro-CT system was adapted to provide high
      resolution, three-dimensional (3D) images of intact and fractured BSCC valve
      outlet struts in vitro. System modifications included use of a tungsten anode X
      ray source to achieve sufficiently high X-ray energies to overcome attenuation
      within the metal structures, and a hafnium filter to minimize the imaging
      artifact caused by X-ray beam hardening. For rotating the valve for tomographic
      scanning, special alignment procedures were developed to maintain the region of
      interest within the field of view. Typical 3D images of the outlet struts were
      composed of cubic voxels, 10 microm on a side. Image analysis and display
      software was used to view the outlet struts and the fractures from several
      perspectives, including en-face images of fracture surfaces. RESULTS: 3D volume
      data representations of the SLS and intact outlet struts were obtained,
      facilitating identification of fracture location and geometry. Enface images of
      the fracture surfaces were also generated. Several different fracture geometries
      were observed, such as fractures with and without longitudinal gaps between the
      fracture faces, and fractures with and without lateral displacement between the
      faces. En-face views showed varying degrees of roughness on fracture faces.
      CONCLUSION: This application of micro-CT to image outlet strut fractures in BSCC
      valve explants demonstrates the value of this method for fracture
      characterization in vitro, including visualization of fracture faces of SLS
      struts without physical sectioning. Although the method is not suitable for
      clinical use because it requires high-intensity X-rays, micro-CT can serve as a
      tool to understand further any failure mechanisms, and to aid the development of
      clinical differentiation methods.

PMID- 11843497
TI  - The CarboMedics prosthetic heart valve: experience with 1,084 implants.
AB  - BACKGROUND AND AIM OF THE STUDY: The study aim was to evaluate our clinical
      experience with the CarboMedics heart valve prosthesis. METHODS: Between October
      1991 and December 2000, 942 consecutive patients (514 males, 428 females; mean
      age 58+/-11 years; range: 6-78 years) underwent mechanical valve implantation
      with the CarboMedics prosthesis. Preoperatively, 47% of patients were in NYHA
      class III and 22% in class IV; in addition, 134 patients (14.2%) had undergone a
      previous cardiac operation. Aortic valve replacement (AVR) was performed in 469
      patients (49.8%), mitral valve replacement (MVR) in 330 (35.0%), double valve
      replacement (DVR) in 142 (15.1%), and isolated tricuspid valve replacement (TVR)
      in one patient. Eighty-eight patients (9.3%) underwent associated myocardial
      revascularization. Mean cardiopulmonary bypass and aortic cross-clamp times for
      the entire group were 107+/-39 min and 74+/-24 min, respectively. RESULTS:
      Overall early mortality was 2.3% (6/469 AVR, 1.2%; 12/330 MVR, 3.6%; 4/142 DVR,
      2.8%). Late mortality was 3.1% (n = 29; including 17 cardiac deaths (10 were
      valve-related). Mean follow up was 66+/-31 months (range: 1-109 months), and was
      98% complete yielding a total follow up of 4959 years. Actuarial survival at five
      years for the entire group was 89.3+/-1.6% (AVR 91.1%, MVR 86.4%, DVR 90.5%).
      Thromboembolism occurred in 26 patients (2.8%, 0.52%/pt-year) and major
      hemorrhagic events in 20 (2.1%, 0.4%/pt-year). Nine patients (0.9%) required a
      reoperation, in three cases (0.3%) after Staphylococcus epidermidis-mediated
      endocarditis. No structural deterioration occurred. Among 891 survivors, 94% of
      the patients are currently in NYHA classes I or II (p <0.05). CONCLUSION: This
      study confirmed the safety and reliability of the CarboMedics mechanical valve
      prosthesis, even in old age groups. This bileaflet prosthesis showed no
      structural deterioration, and a low incidence of overall complications.

PMID- 11843499
TI  - Value of intraoperative transesophageal echocardiography in preventing serious
      complications during valvular surgery. A report of four cases.
AB  - The value of routine transesophageal echocardiography (TEE) was confirmed by the
      detection of rare and potentially serious complications in four of 136 patients
      (2.9%) undergoing valvular surgery. In case 1, one leaflet of a St. Jude Medical
      (SJM) valve implanted in the mitral position was stuck in the closed position;
      normal valve function was restored by 90 degrees rotation of the prosthesis. In
      case 2, moderate regurgitation was observed after mitral valve replacement with a
      Carpentier-Edwards pericardial bioprosthesis. The mitral valve was replaced with
      a SJM valve; regurgitation was proved due to a suture loop jamming. In case 3,
      perivalvular leakage was detected after aortic valve replacement for infective
      endocarditis; an additional suture stopped the leakage. In case 4, a foreign body
      was observed in the left atrium after aortic valve replacement for calcified
      aortic stenosis. The left atrium was re-opened, and a free-floating portion of
      the calcified native aortic valve was identified and removed. Routine
      intraoperative TEE in valve surgery permits the identification and management of
      potentially serious complications before discontinuing cardiopulmonary bypass.

PMID- 11843498
TI  - Experimental aortic regurgitation in rats under echocardiographic guidance.
AB  - BACKGROUND AND AIM OF THE STUDY: Experimental aortic regurgitation (AR) induced
      by retrograde perforation of the aortic leaflets has been used as an animal model
      of volume overload, but causes high mortality. In the past, AR was induced under
      hemodynamic guidance, but echocardiography can be used to guide the investigator
      as well as grade AR severity and monitor left ventricular function. The study aim
      was to assess the value of echocardiography in experimental AR in rats. METHODS:
      Sixty-six Wistar rats (bodyweight 250-275 g) underwent perforation of the aortic
      leaflets via a right transcarotid approach to induce moderate to severe AR.
      Transthoracic echocardiographic guidance was used to assess catheter location,
      degree of AR, ventricular function and complications. RESULTS: Echocardiographic
      images were easily obtained and of excellent quality (M-mode, two-dimensional and
      complete Doppler evaluation). Catheter location, movement and guidance during
      aortic valve perforation were straightforward, and AR gradation and ventricular
      function easily assessed. Procedural complications and causes of death were
      identified. Had hemodynamic criteria been used, 24% of AR cases would have been
      misgraded. With echocardiography, the overall mortality rate was 17% (<10% in the
      last 25 animals). CONCLUSION: Echocardiographic guidance is mandatory for
      protocols of experimental AR. Using this technique, the procedure is simplified,
      and is more accurate, more reproducible and safer for the animals.

PMID- 11843500
TI  - Valve morphology and the rate of progression in aortic stenosis.

PMID- 11843501
TI  - Septal-lateral annular cinching ('SLAC) reduces mitral annular size without
      perturbing normal annular dynamics.
AB  - BACKGROUND AND AIM OF THE STUDY: Septal-lateral (S-L) mitral annular diameter
      reduction is thought to be central to the efficacy of ring annuloplasty in
      correcting functional mitral regurgitation (MR), but rings perturb mitral annulus
      (MA) dynamic motion and limit posterior leaflet excursion. The effects of S-L
      annular cinching ('SLAC'), a novel method for mitral annular reduction, were
      investigated. METHODS: Eight adult sheep had multiple radioopaque markers placed
      on the left ventricle, leaflet edges, and around the MA. The S-L trans-annular
      suture was anchored to the mid-septal MA and externalized through the mid-lateral
      MA and left ventricular wall. Animals were studied immediately postoperatively
      with biplane videofluoroscopy before and after suture cinching to reduce annular
      size. MA area (MAA) and S-L dimension were calculated throughout the cardiac
      cycle from the annular marker coordinates. MAA contraction (AMAA) was expressed
      as percentage decrease from maximum to minimum MAA. Anterior (AML) and posterior
      (PML) leaflet angular excursion were calculated as the change in angle between
      each leaflet edge marker and the S-L annular dimension during the cardiac cycle.
      MA folding was calculated as the change in distance during systole of the mid
      septal annular marker from a plane fitted to the lateral MA markers. RESULTS:
      SLAC reduced end-diastolic (ED) S-L diameter (21.6+/-2.8 versus 17.1+/-2.6 mm; p
      = 0.0005) and ED MAA (618+/-126 versus 525+/-114 mm2; p = 0.0004), but did not
      perturb normal AMAA (15.8+/-4.1 versus 15.1+/-4.8%; p = 0.4), annular flexion
      (2.0+/-0.7 versus 1.8+/-0.7 mm; p = 0.3) or AML excursion (55+/-7 versus 53+/-7
      degrees; p = 0.1). PML excursion was decreased only slightly (52+/-11 versus 44+/
      12 degrees; p = 0.002). CONCLUSION: SLAC substantially reduced S-L annular size,
      but without perturbing normal MA contraction dynamics, MA flexion, or anterior
      leaflet excursion. This novel surgical method might represent an alternative to
      mitral annuloplasty for patients with certain types of mitral pathology.

PMID- 11843502
TI  - Surgical management of acute mitral valve regurgitation due to post-infarction
      papillary muscle rupture.
AB  - BACKGROUND AND AIM OF THE STUDY: Acute myocardial infarction associated with
      mitral papillary muscle rupture and cardiogenic shock carries a high mortality.
      Data relating to early and late survival after emergency mitral valve surgery and
      concomitant complete coronary artery revascularization in this patient population
      were analyzed. METHODS: Between January 1988 and December 1998, 21 consecutive
      patients (mean age 62+/-9.7 years) underwent emergency coronary and concomitant
      mitral valve surgery for acute myocardial infarction and mitral papillary muscle
      rupture associated with cardiogenic shock. Mitral valve replacement was performed
      in 19 patients (90%), and mitral valve repair in two (10%). An average of 2.2
      distal anastomoses per patient was performed. Revascularization was complete in
      19 patients (90%). Preoperatively, intra-aortic balloon pumping was used in 11
      patients (52%), and two (10%) had salvage surgery when arriving at the operating
      room under cardiopulmonary resuscitation. Early and late follow up was complete;
      mean follow up was 5+/-3 years (range: 16 months to 12 years). RESULTS: Thirty
      day mortality was 19% (4/21), with two cardiac-related early deaths (10%). Early
      morbidity included perioperative stroke in 6% (1/17), myocardial infarction in 6%
      (1/17), and need for hemodialysis in 18% (3/17). There were three late deaths;
      one was cardiac-related. Actuarial survival at one, five and 10 years was 81, 68
      and 56%, respectively. All survivors were in NYHA class I or II. CONCLUSION:
      Emergency surgery for acute post-infarction mitral papillary muscle rupture is
      justified, even as a salvage procedure. Concomitant mitral valve surgery and
      complete coronary artery revascularization achieve acceptable survival rates and
      satisfactory functional results.

PMID- 11843503
TI  - Mitral valve surgery for acute papillary muscle rupture following myocardial
      infarction.
AB  - BACKGROUND AND AIM OF THE STUDY: Acute papillary muscle rupture (PMR) is a rare
      but fatal complication of myocardial infarction (MI). Surgery represents the best
      treatment option, but carries a high risk. Our experience of emergency mitral
      valve surgery in patients with acute PMR following MI during the past 22 years is
      reviewed. METHODS: Between 1978 and 2000, 33 patients (20 males, 13 females; mean
      age 64 years; range: 46-80) underwent emergency surgery for acute post-infarct
      PMR in our institution. The site of MI was anterior in three patients and
      inferior in 30. Preoperatively, 17 patients had an intra-aortic balloon pump
      (IABP) inserted, 26 were on inotropic support, and 17 were ventilated. Twenty
      patients (61%) underwent concomitant coronary bypass grafting (CABG). The valve
      was replaced in 31 patients and repaired in two. Mean (+/- SD) duration of follow
      up was 63+/-54 months (range: 0-183 months). RESULTS: Early mortality (in
      hospital) was 21% (n = 7). Factors associated with significant risk of early
      mortality included raised preoperative serum creatinine (p = 0.02), need for
      preoperative inotropic support (p = 0.03) and preoperative ventilation (p =
      0.03). Raised preoperative serum creatinine remained significant on multiple
      logistic regression (p = 0.04). Postoperatively, 21 patients required an IABP.
      Mean duration of intensive care unit stay was 4+/-2.5 days (range: 0-10 days).
      Survival, including in-hospital mortality, at one, five and 10 years was 75+/
      7.4, 65+/-8.6 and 32+/-9.7%, respectively. Four patients required valve-related
      reoperation (three for a paraprosthetic leak, one for failed repair). CONCLUSION:
      Patients with acute post-infarct PMR present in a severely compromised state.
      Early mortality is high, but the intermediate outcome is encouraging for
      operative survivors.

PMID- 11843504
TI  - Flexibility of the mitral annulus with the Duran ring at six years post
      implantation.
AB  - BACKGROUND AND AIM OF THE STUDY: Although, in theory, the mitral annulus with the
      Duran flexible ring should change size and shape during the cardiac cycle, no
      clinical reports are available of such flexibility several years after surgery.
      The study aim was to evaluate mitral annulus flexibility at medium-term follow up
      after surgery. METHODS: Eleven patients (mean age 60+/-8 years) were enrolled for
      this study. All were in sinus rhythm and had less than mild residual mitral
      regurgitation. The mean time between study and mitral valve repair was 6.0+/-2.4
      years. Three sizes of Duran ring were used (three size 27, six size 29, and two
      size 31). All patients were studied with transesophageal echocardiography. The
      mitral annulus was reconstructed 10 times around a single axis of rotation during
      the cardiac cycle, using published methods. The area, circumferential length and
      shape of the mitral annulus were analyzed at various times during the cardiac
      cycle. RESULTS: A significant change in mitral annular area occurred during the
      cardiac cycle; the maximum to minimum reduction was 23+/-8% (p <0.001). The area
      and circumferential length of the mitral annulus in patients with size 29 Duran
      rings changed from 8.2+/-1.3 to 6.2+/-1.3 cm2 (p <0.001) and from 11.8+/-1.1 to
      9.9+/-0.8 cm (p <0.001), respectively. Three-dimensional reconstruction of the
      mitral annulus showed it to retain its non-planar shape, but the shape to change
      significantly during the cardiac cycle. CONCLUSION: The mitral annulus with a
      Duran ring remained flexible and retained its non-planar configuration at six
      years after implantation.

PMID- 11843505
TI  - Long-term results with the Biocor-SJM stentless porcine aortic bioprosthesis.
AB  - BACKGROUND AND AIM OF THE STUDY: The study aim was to update the clinical
      analysis of hemodynamic performance, structural failure and survival in patients
      undergoing aortic valve replacement (AVR) with a composite aortic, aldehyde
      tanned, stentless porcine bioprosthesis. METHODS: Between January 1990 and March
      2001, 247 patients underwent AVR with aortic stentless valves. Patient
      demographic and clinical analysis included age, sex, valve lesion, valve size,
      pre- and postoperative NYHA class, hospital morbidity, mortality, operative data
      and duration of hospitalization. RESULTS: Mean patient age was 47.3 years; 71% of
      patients were males, and 45% had aortic insufficiency. The incidence of rheumatic
      heart disease requiring surgery was 41.7%. In 23% of patients surgery was
      indicated due to aortic stented bioprosthetic dysfunction. Preoperatively, 81% of
      patients were in NYHA classes III and IV. Mean follow up was 5.9+/-2.8 years
      (range: 1 month to 11.4 years); total follow up was 1,392 patient-years (98%
      complete). The valve size used was < or =25 mm in 75.3% of patients. The mean
      intensive care unit stay was 2.6 days; mean hospital stay was 10.7 days. Hospital
      mortality was 4.0% and late death 6.1%. There were no valve-related deaths.
      Postoperatively, the mean aortic effective orifice area (EOA) was 1.71 cm2, the
      mean peak transvalvular gradient 17.1 mmHg, and the mean transvalvular gradient
      9.0 mmHg; the left ventricular mass index (g/m2) was 174 and 117 before and after
      surgery respectively. The rate of leaflet tissue degeneration was 0.9%, and seen
      as mild by echocardiographic follow up. Actuarial survival at almost 12 years was
      91%, and freedom from reoperations was approximately 99%. CONCLUSION: Patients
      with aortic stentless valves have hemodynamic benefits seen as larger aortic EOA,
      low transvalvular gradients, satisfactory left ventricular remodeling with
      significant reduction of left ventricular mass, low complication rate, low
      reoperation rate, lower leaflet tissue degeneration rate, and no valve-related
      mortality. A longer follow up is required to confirm these benefits.

PMID- 11843506
TI  - Transvalvular velocities after full aortic root replacement: results from a
      prospective randomized trial between the homograft and the Medtronic Freestyle
      bioprosthesis.
AB  - BACKGROUND AND AIM OF THE STUDY: Unstented bioprostheses offer better
      hemodynamics after aortic valve replacement. It has been reported recently that
      subcoronary implantation of the Freestyle valve may result in increased
      transvalvular velocities. In a prospective randomized trial, transvalvular
      velocities were investigated after implantation of a homograft or a Medtronic
      Freestyle bioprosthesis as a full root. METHODS: A total of 137 patients was
      randomized to receive either a homograft (group H, n = 64) or a Freestyle (group
      F, n = 73) root replacement. Echocardiographic investigations were performed at
      six weeks, six months, and then yearly after surgery. Transvalvular and
      subvalvular velocities were recorded from each echocardiogram. RESULTS: At follow
      up, none of the patients showed high transvalvular or subvalvular velocities (>2
      m/s). At six weeks after surgery the transvalvular velocity was 1.5+/-0.3 m/s in
      group H (n = 51) and 1.7+/-0.3 m/s in group F (n = 56) (p = NS), while
      subvalvular velocities were 0.9+/-0.3 and 1.0+/-0.3 m/s, respectively (p = NS).
      These findings remained constant up to the three-year follow up, when
      transvalvular velocity was 1.6+/-0.4 m/s in group H (n = 10) and 1.6+/-0.2 m/s in
      group F (n = 15) (p = NS). Subvalvular velocities were 0.9+/-0.1 and 0.9+/-0.1
      m/s, respectively (p = NS). CONCLUSION: Full aortic root replacement and
      reimplantation of the coronary arteries either with the Medtronic Freestyle or
      the homograft valve produces near-normal transvalvular velocities less than were
      reported for the Freestyle in the subcoronary implantation.

PMID- 11843507
TI  - Evaluation of left ventricular function and mass after Medtronic Freestyle versus
      homograft aortic root replacement using cardiovascular magnetic resonance.
AB  - BACKGROUND AND AIM OF THE STUDY: Regression of left ventricular hypertrophy (LVH)
      after aortic valve replacement has traditionally been measured by
      echocardiography. However, cardiovascular magnetic resonance (CMR) can be used to
      measure left ventricular function and mass more accurately and reproducibly. This
      translates into fewer patients being needed to demonstrate significant changes.
      The study aim was to demonstrate the feasibility of using CMR to measure left
      ventricular mass index (LVMI) and function in patients from a prospective
      randomized trial, and to compare homografts with the Medtronic Freestyle root
      replacement. METHODS: Among 23 patients recruited, 17 had LVMI and function (end
      diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV) and
      ejection fraction (EF)) measured pre- and postoperatively using CMR (eight
      homograft, nine Freestyle). RESULTS: Significant regression of LVH was seen in
      both groups one year postoperatively (homograft LVMI 145+/-44 g/m2 preoperative
      versus 83+/-23 g/m2 one year postoperatively; Freestyle LVMI 140+/-28 g/m2 versus
      93+/-21 g/m2, respectively). At six months there was significant regression in
      the xenograft group (from 140+/-28 to 106+/-22 g/m2; p <0.05) and a trend towards
      regression in the homograft group (from 145+/-44 to 103+/-25 g/m2; p = NS). There
      was also a trend towards a reduction in EDV, ESV and SV, and an increase in EF
      over one year in both groups. CONCLUSION: Regression of LVH was measured using
      CMR in patients after aortic root replacement and coronary implantation with the
      homograft and Medtronic Freestyle root replacement. Despite the small number of
      patients studied, it was possible to demonstrate the extent and pattern of
      regression of left ventricular mass in the two groups.

PMID- 11843508
TI  - Aortic distensibility after aortic root replacement assessed with cardiovascular
      magnetic resonance.
AB  - BACKGROUND AND AIM OF THE STUDY: The changes in geometry of the aortic root
      during the cardiac cycle are thought to be essential for optimal valve function,
      both in terms of leaflet stress and dynamic behavior. Using cardiac magnetic
      resonance (CMR), the study aim was to determine aortic root distensibility of the
      homograft (group H) and the Medtronic Freestyle xenograft (group F) after aortic
      root replacement, from a prospective randomized trial. METHODS: CMR was performed
      in 15 patients (six homografts, nine Freestyle) at six months and one year after
      surgery. Percentage change in aortic radius (PCR) and pressure strain elastic
      modulus (PSEM) were measured as indices of distensibility, and results related to
      left ventricular mass (LVM). RESULTS: At six months after surgery, mean PCR was
      12+/-2.5 in group H and 12.9+/-6.1 in group F (p = NS), and PSEM was 428.5+/-69.8
      and 493.5+/-72.7 g/cm2, respectively (p = NS). PCR was reduced to 10+/-1.7% in
      group H, and by 8.5+/-2.8% in group F (p = NS), while PSEM was increased to
      520.5+/-87.3 and 825+/-420.4, respectively (p = NS) at the one-year follow up.
      Regression analysis showed a correlation between PCR and LVM (r = 0.52, p = 0.08)
      and LVM index (r = 0.46, p = 0.14), respectively. In addition, there was a
      relationship between PSEM, LVM and LVM index, suggesting that the stiffer the
      root wall, the higher the postoperative LVM. CONCLUSION: Up to one year after
      aortic root replacement, the wall of both the allogenic and xenogenic valves
      retained near-normal distensibility. For the first time, a correlation was
      demonstrated between the elastic properties of the aortic root and LVM. The
      longer-term behavior and clinical implications of these findings require further
      investigation.

PMID- 11843509
TI  - Characteristics of compressive strains in porcine aortic valves cusps.
AB  - BACKGROUND AND AIM OF STUDY: Previous studies in our laboratory have revealed the
      presence of compressive strains at the base of the non-coronary (NC) cusp of
      porcine aortic valves. Since these strains have been shown to damage
      bioprosthetic valve tissue, the mechanism by which they are induced in valve
      tissues should be investigated. METHODS: Whole porcine aortic valves were
      pressurized and the induced strain patterns measured on aortic valve cusps and
      roots. Measurements were made before and after trimming of excess ventricular
      muscle and mitral valve tissue. RESULTS: Negative (compressive) radial strains
      were found only in the NC cusp. Trimming of surrounding muscle increased the
      magnitude of both the tensile circumferential strains and compressive radial
      strains in the NC cusp. The left and right coronary cusps (LC, RC respectively)
      had similar positive radial and circumferential strains, and trimming had
      inconsistent effects on the strain patterns. Trimming of the aortic root
      increased root strains adjacent to the NC cusp, thus increasing positive
      circumferential strains and negative radial strains in the NC cusp. Analysis of
      images obtained during loading indicated that a wrinkle formed at the base of the
      NC cusp in 66% of cases in which negative strains were observed. CONCLUSION:
      Negative radial strains were induced in the NC cusp as it stretched
      circumferentially during static pressurization. In many valves, negative strains
      resulted from radial folding or wrinkling of the valve cusp. Since the RC and LC
      cusps had circumferential and radial strains that were not similar to those of
      the NC cusp, it is likely that the NC cusp has a different internal fibrous
      organization.

PMID- 11843510
TI  - Q fever endocarditis: over 14 years of surgical experience in a referral center
      for rickettsioses.
AB  - BACKGROUND AND AIM OF THE STUDY: Q fever endocarditis caused by Coxiella burnetii
      is the most important etiology of negative blood culture endocarditis. Without
      specific clinical findings, diagnosis is difficult and prevalence of this life
      threatening disease is underestimated. METHODS: Q fever endocarditis was assessed
      in 19 patients (15 men, four women; age range: 36-79 years) by evaluating
      clinical and echocardiographic criteria and specific serology. All patients had
      evidence of pre-existing valvular disease, and 10 had a valvular prosthesis.
      Diagnosis was assessed in: the presence of unexplained fever (n = 5), heart
      failure with valvular dysfunction (n = 10), hemolysis (n = 1), glomerulonephritis
      (n = 1) and stroke (n = 2). A late diagnosis was made in eight patients, either
      during or after surgery. RESULTS: In all cases, usual blood cultures remained
      negative, despite specific serology being positive. Transthoracic and
      transesophageal echocardiography were conclusive in only six cases (four
      vegetations, two periannular abscesses). Surgery was indicated in 15 patients for
      heart failure or valvular dysfunction (n = 12), hemolysis (n = 1) and periannular
      abscess (n = 2). Intraoperative findings were suggestive of endocarditis in seven
      cases; valvular cultures were positive in 92% of cases. All patients were treated
      with combined doxycycline/ hydrochloroquine or quinolone, for a mean of 24 months
      (range: 6-60 months). Mean follow up was 40 months (range: 6-144 months). Two
      patients died from heart failure, one patient was lost to follow up, and 16
      patients had no late relapses. CONCLUSION: Q fever is an underestimated cause of
      endocardititis, and early diagnosis is the key to good prognosis. The need for
      systematic serologic examination in case of valvular dysfunction, with or without
      endocarditis symptoms, is emphasized.

PMID- 11843511
TI  - The advantage of repair of mitral valve in acute endocarditis.
AB  - BACKGROUND AND AIM OF THE STUDY: Mitral valve repair offers a survival benefit
      compared with valve replacement in surgery for non-infectious mitral
      regurgitation. It is unclear whether repair offers an advantage for patients
      undergoing mitral valve surgery for active endocarditis. Morbidity and mortality
      (early and late) and event-free survival were compared between the repair and
      replacement groups. METHODS: Between September 1986 and July 1999, 44 patients
      with acute native mitral valve endocarditis underwent surgery; 28 patients had
      valve replacement, and 16 underwent repair. Nine patients had complex repairs
      including replacement of a portion of the leaflet with prosthetic patch,
      placement of artificial chordae, resection of a portion of both leaflets, and/or
      reconstruction of a commissure. The remainder had simple repairs. RESULTS:
      Preoperative characteristics and indications for surgery between the two groups
      were similar. There were six in-hospital (21%) and six late cardiac deaths (21%)
      in the valve replacement group, but no early deaths or late cardiac deaths in the
      repair group (p <0.05). Independent risk factors for early and late death were
      need for associated procedures (p <0.03) and mitral valve replacement (p <0.05).
      Additional risk factors for late death were diabetes mellitus (p = 0.005) and
      hemodynamic instability as an indication for surgery (p = 0.047). Five patients
      undergoing valve replacement required reoperation due to recurrent endocarditis,
      compared with none in the repair group (p = 0.065). Mean follow up was 39+/-33
      months in the repair group, and 57+/-51 months in the replacement group.
      CONCLUSION: Early and late mortality and event-free survival were better in
      patients undergoing mitral valve repair compared with replacement for acute
      endocarditis. Valve repair should be carried out whenever possible in this
      patient group.

PMID- 11843513
TI  - Cardiac valve surgery.

PMID- 11843512
TI  - In-vitro and in-vivo activity of antimicrobial-coated prosthetic heart valve
      sewing cuffs.
AB  - BACKGROUND AND AIM OF THE STUDY: Prosthetic valve endocarditis (PVE) is a
      relatively uncommon but very serious condition. As bacterial colonization of the
      prosthetic heart valve sewing cuff can be a prelude to the clinical occurrence of
      PVE, antimicrobial coating of the sewing cuff may be beneficial. The study aims
      were to examine the antimicrobial activity in vitro and anti-infective efficacy
      in vivo of prosthetic heart valve sewing cuffs coated with minocycline and
      rifampin. METHODS: Zones of inhibition by antimicrobial-coated sewing cuffs were
      assessed in vitro against Staphylococcus epidermidis, S. aureus, Enterococcus
      faecalis, Pseudomonas aeruginosa and Candida albicans. The ability of
      subcutaneously implanted devices coated with minocycline and rifampin to resist
      colonization and infection by P. aeruginosa was also examined in a rabbit model.
      RESULTS: Antimicrobial-coated sewing cuffs produced zones of inhibition against
      all tested organisms. Coated devices were significantly less likely than uncoated
      devices to become colonized (2/24; 8% versus 20/24; 83%; p <0.001) or to cause
      device-related infection (0/24; 0% versus 18/24; 75%; p <0.001) and device
      related abscess (0/24; 0% versus 10/24; 42%; p <0.001) due to P. aeruginosa.
      CONCLUSION: Prosthetic heart valve sewing cuffs coated with minocycline and
      rifampin provide broad-spectrum antimicrobial activity in vitro, and are anti
      infective in vivo against P. aeruginosa. These results encourage the clinical
      evaluation of these sewing cuffs.

PMID- 11843514
TI  - Mitral valve repair for degenerative disease.
AB  - Degenerative mitral valve disease is the most common cause of mitral
      regurgitation in North America. Using techniques developed by Carpentier and
      others, up to 90% of degenerative mitral valves can be repaired. These valves are
      characterized by annular dilatation and chordal rupture or elongation; chordal
      changes are mainly localized to the posterior leaflet. The most common repair
      technique for posterior leaflet prolapse is quadrangular resection. When the
      leaflet is >1.5 cm long, a sliding repair is added to reduce the risk of systolic
      anterior motion. Anterior leaflet prolapse is usually treated by transfer of
      chords from the posterior leaflet or adjacent areas of the anterior leaflet.
      Other useful techniques for correction of anterior leaflet prolapse are creation
      of artificial chords and the Alfieri edge-to-edge repair. Chordal shortening is
      rarely employed as it jeopardizes repair durability. Annuloplasty accompanies all
      repairs. A posterior annuloplasty provides results equivalent to those obtained
      with a circumferential annuloplasty. Flexible annuloplasty has theoretical
      advantages, but clinical benefits have not been shown. After mitral valve repair
      for degenerative disease, 10-year freedom from reoperation is 93%. Risk of
      reoperation is increased by anterior leaflet prolapse, chordal shortening,
      failure to use an annuloplasty, and lack of intraoperative echocardiography. In
      the ideal situation, when posterior leaflet resection is corrected by
      quadrangular resection with annuloplasty and the result is confirmed by
      intraoperative echocardiography, the 10-year durability is 98%.

PMID- 11843515
TI  - Statistical analysis of heart valve outcomes.
AB  - Statistics is a rapidly growing field utilizing thousands of data analysis
      functions, though a relatively few are used in the majority of cardiac surgical
      studies. Dr. Wechsler recently published a list of the statistical terms which
      are important for cardiothoracic surgeons to be familiar with. These can be
      grouped into 3 categories: General concepts; Summary and test statistics; and
      Special techniques. The last category includes three techniques which are widely
      used to describe the long-term results of heart valve series: Hazard functions,
      Kaplan-Meier event-free curves, and "Actual" event-free curves. Some conclusions
      from a review of these techniques are: (1) an event with a non-constant hazard
      should not be described using "Linearized" rates (the Weibull distribution adds a
      parameter to accommodate changing hazard); (2) for non-fatal events, "Actual"
      analysis provides the true event probability, which the Kaplan-Meier
      overestimates. These methods are used in the analysis of published heart valve
      series to conclude that: (1) the wide scatter in complications rates with the
      same valve models implicates factors other than the valve; (2) the earliest
      porcine series had low mean ages and low durability compared with later series.

PMID- 11843516
TI  - Surgical treatment of the ischemic mitral valve.
AB  - The best management for moderate mitral regurgitation (MR) at the time of
      coronary revascularization remains controversial. During the era preceding
      standardization of mitral annuloplasty, coronary artery bypass grafting (CABG)
      alone was the most common strategy for ischemic MR. This approach avoided mitral
      valve replacement, and there was an expectation that myocardial revascularization
      would improve papillary muscle function and valve performance. Long-term follow
      up revealed, however, a relationship between residual MR and mortality. Recent
      studies have further refined management of ischemic MR. It is now understood that
      Carpentier type IIIb dysfunction is the basis for ischemic MR, and that a
      reduction remodeling annuloplasty can improve leaflet coaptation in this setting.
      Mortality after combined CABG and mitral annuloplasty has decreased in our
      institution from 14% to 4% over the past decade. Furthermore, a strategy of CABG
      alone will leave a significant number of patients (approximately 40%) with
      moderate to severe MR. Our current approach is to explore all valves at the time
      of CABG with documented grade 3+ MR on preoperative transthoracic
      echocardiography. Intraoperative transesophageal echocardiography (TEE)
      underestimates moderate MR. In patients with a lesser degree of MR,
      intraoperative provocative testing guides our valve strategy. Severe left
      ventricular dysfunction and a history of congestive heart failure will also
      influence the decision regarding valve exploration at the time of CABG. A
      prospective randomized trial between CABG and CABG + mitral annuloplasty is
      necessary to further define the best management strategy for patients with
      moderate ischemic MR.

PMID- 11843517
TI  - Mitral reconstruction in cardiomyopathy.
AB  - Functional mitral regurgitation (MR) is a significant complication of end-stage
      cardiomyopathy, and may affect most heart failure patients as a pre-terminal or
      terminal event as it develops secondary to a change in the annular-ventricular
      apparatus and altered ventricular geometry; this results in incomplete leaflet
      coaptation.. Historically, surgery in MR patients was mitral valve replacement,
      but the adverse effects on LV systolic function of interrupting annulus-papillary
      muscle continuity was poorly understood. At the University of Michigan (1993
      2000), 140 patients with end-stage cardiomyopathy and refractory MR underwent
      mitral valve repair with an undersized flexible annuloplasty ring. All were in
      NYHA class III/IV despite receiving maximal medical therapy, and had severe LV
      systolic dysfunction (ejection fraction (EF) <25%). Overall operative mortality
      was 5%. There were five 30-day mortalities (one intraoperative death due to right
      ventricular failure, one cardiac failure, one stroke, two multisystem organ
      failure). Five patients required intra-aortic balloon pump IABP support, but no
      patients required a LV assist device. Mean follow up was 38 months (range: 1-68
      months); one- and two-year actuarial survival was 80% and 70%, respectively.
      There were 26 late deaths. At postoperative echocardiography the mean transmitral
      gradient was 3 +/- 1 mmHg (range: 2-6 mmHg). At two-year follow up, all patients
      were in NYHA class I/II, with mean EF 26%. NYHA class was improved in all
      patients, and all reported subjective improvement in functional status.
      Improvements were shown in LV EF, cardiac output, and end-diastolic volumes, with
      reduced sphericity index and regurgitant fraction. Though significant undersizing
      of the mitral annulus was used to over-correct for the zone of coaptation, no
      mitral stenosis was induced, nor was any systolic anterior motion (SAM) noted.
      SAM was avoided due to widening of the aortomitral angle and increased LV size
      seen in myopathic patients. In conclusion, surgical therapies of heart failure
      are rapidly expanding and evolving. As a result of improvements in preoperative
      selection, intraoperative techniques and postoperative care, high mortality and
      morbidity after surgical intervention in patients with end-stage heart disease no
      longer apply. By combining operative techniques with optimal medical management
      of heart failure, good outcome can avoid or postpone transplantation. This
      strategy will help to preserve the limited number of donor organs for those
      patients with no other surgical or medical alternatives.

PMID- 11843518
TI  - Are mechanical valves safe to use in older patients?

PMID- 11843519
TI  - Decision-making in the choice of heart valve for replacement in patients aged 60
      70 years: twenty-year follow up of the St. Jude Medical aortic valve prosthesis.
AB  - BACKGROUND AND AIM OF THE STUDY: The choice of a cardiac valve for patients with
      aortic valvular pathology remains controversial. Younger patients may be at risk
      for long-term complications from chronic anticoagulation yet require prosthesis
      longevity, while older patients may not outlive a bioprosthesis. To gather
      information to help decision-making, the 20-year experience of aortic valve
      replacement (AVR) with the St. Jude Medical (SJM) valve by the surgeons of
      Cardiac Surgical Associates, P.A., was reviewed. METHODS: Cardiac Surgical
      Associates Research Foundation maintains a database of all patients undergoing
      valve replacement with the SJM aortic prosthesis since the world's first implant
      in October 1977. Patient follow up is conducted by questionnaire and/or telephone
      interview. The 20-year follow up period ended in October 1997. Follow up is 96.3%
      complete, and extends to 13,208 patient-years. RESULTS: A total of 2,390 aortic
      valves (1,500 in males, 890 in females) were replaced in the period studied.
      Among these patients, 1,419 had isolated AVR, whilst the remainder had AVR plus
      coronary artery bypass (CAB) or other procedures. The mean age was 63 +/- 14
      years for AVR, and 70 +/- 10 years for AVR/CAB. Over the 20-year follow up
      period, freedom from valve-related events for the entire group was:
      thromboembolism, 97%; anticoagulant-related hemorrhage, 94%; valve thrombosis,
      99.7%; prosthetic valve endocarditis, 99.2%; and paravalvular leak, 99.6%.
      Freedom from structural failure was 100%. Mortality for these events was low (15
      deaths among 250 events; 6%). Overall survival at 5, 10, 15 and 19 years was 82,
      66, 51 and 45% respectively for isolated AVR, and 72, 45, 25 and 15% respectively
      for AVR/CAB. CONCLUSION: The SJM valve has excellent hemodynamics and a low
      incidence of valve-related complications. Improvements in anticoagulation
      monitoring with the newly introduced and funded home monitoring program, as well
      as the introduction of newer and more effective antiplatelet drugs, will improve
      the safety of patients requiring chronic anticoagulation. With durability
      unquestioned, these long-term data show the SJM valve to be an excellent choice
      for AVR in patients aged 60-70 years.

PMID- 11843521
TI  - Assessing options for the small aortic root.
AB  - Valve selection for the small aortic root is a multifactorial process.
      Considerations include the effective orifice (EOA) of the implanted valve,
      annular size, body surface area (BSA), and valvular outflow tract of each
      patient. To decide if a valve is adequate for a patient, the valve EOA and
      patient BSA are used to calculate the indexed EOA (EOA/BSA). An indexed EOA <0.85
      is associated with significant increases in mean systolic gradient with increase
      in cardiac output. The gradient remains low when indexed EOA is >0.85, leading to
      improved left ventricular mass reduction and decreased long-term risk of
      arrhythmias, congestive heart failure, and death. Biologic valves are usually
      used in patients aged over 65 years. Stented biologic valves tend to have a low
      EOA for their size. A 21-mm pericardial valve has an indexed EOA of 0.81 when
      implanted in a 1.6-m, 58-kg woman, and 0.69 in a 1.7-m, 72-kg man. Stentless
      valves (xenograft and homograft) have excellent EOAs and consequently very low
      gradients with good ventricular mass reduction. This allows for insertion of a
      larger valve, and results in more normal opening and flow dynamics. Hence, the
      best approach in over 65-year-old aortic valve patients when using a biologic
      valve is a stentless subcoronary implant. If this is not possible for anatomic
      reasons, a stented valve with an indexed EOA >0.85 is the best alternative. An
      option is root replacement with a xenograft or homograft, but the operative risk
      is significantly increased. The decision in younger patients (aged <65 years) is
      more complex. In-vivo EOAs for mechanical valves vary greatly; the St. Jude HP
      and Regent valves have consistently excellent EOAs. Recent results with the St.
      Jude Regent valve show gradients and left ventricular mass reduction close to
      those for stentless biologic valves. In a small aortic annulus, the decision must
      be made to use a more efficient valve (e.g. the Regent) or a biologic stentless
      valve, to perform annular enlargement (increasing surgical risk), or to tilt the
      stented valve to be supra-annular in the non-coronary cusp. The subvalvular
      outflow tract should not be ignored. Septal hypertrophy is not uncommon, and may
      increase the gradient across the outflow tract just below the valve. Finally,
      suture techniques (e.g. pledgetted versus interrupted simple sutures) can affect
      the long-term gradient. Pledgetted sutures can draw tissue underneath the valve
      and reduce the EOA. In conclusion, multiple factors must be evaluated when
      deciding which valve to use as a replacement in the small aortic root. These
      include patient age, lifestyle, pregnancy status, and drug compliance, as well as
      the indexed EOA of available prosthetic valves and the surgical procedure
      required for implant.

PMID- 11843520
TI  - Management of mild to moderate aortic stenosis at the time of coronary artery
      bypass grafting.
AB  - An increasing number of patients are referred for coronary artery bypass surgery
      (CABG) with the presence of mild to moderate aortic stenosis (AS). It is well
      accepted that patients with severe AS and coronary artery disease (CAD) should
      undergo combined aortic valve replacement (AVR) and CABG, which carries an
      operative mortality of approximately 5-7%. For patients with CAD and mild AS,
      controversy persists regarding concomitant AVR during CABG. It has been shown
      that AS progresses at a rate of 5-10 mmHg per year, and the valve area decreases
      by about 0.1 cm2 per year. The progression of AS is more rapid in elderly
      patients, in the presence of CAD, and in patients with a calcific degenerative
      etiology. In contrast, patients with congenital bicuspid valves or rheumatic
      pathology demonstrate slower progression of disease. Despite these observations,
      it is difficult to predict reliably the progression of disease for an individual.
      Thus, an attempt should be made to identify patients who are likely to progress
      rapidly from mild to severe AS and who would therefore benefit from AVR/CABG. Our
      approach regarding the decision to perform an AVR/CABG is based on aortic valve
      gradient and area. If the gradient is >25 mmHg, AVR should be considered. If the
      gradient is <10 mmHg, then only CABG is performed. Severities of leaflet
      calcification and leaflet mobility are factors that should be taken into account
      when deciding to perform concomitant AVR/CABG for intermediate gradient (10-25
      mmHg). Additional important variables include the etiology of aortic valve
      disease, the rate of progression of AS, the patient's life expectancy, and
      general condition. For patients with mild AS who are undergoing CABG, a tailored
      approach involving intraoperative transesophageal echocardiography and valve
      inspection is the most appropriate surgical option.

PMID- 11843523
TI  - Anticoagulation self-testing after heart valve replacement.
AB  - The recent introduction of home testing of coagulation status offers a new
      opportunity for improved follow up of patients undergoing chronic anticoagulant
      therapy secondary to valve replacement or other conditions. A growing body of
      data suggests that the ability to monitor the International Normalized Ratio
      (INR) at home results in a greater maintenance of 'in-range' values compared to a
      laboratory-based testing regimen. Additional evidence suggests that this greater
      prevalence of 'in-range' values will translate into a lower frequency of bleeding
      and thrombotic complications. Thus, home INR testing appears to be developing as
      an important diagnostic adjunct for improving the postoperative care of patients
      with prosthetic heart valves, or who are receiving chronic anticoagulation
      therapy for other reasons.

PMID- 11843524
TI  - Long-term outcomes with mechanical and tissue valves.
AB  - Recent publications comparing outcomes in patients receiving tissue or tissue
      heart valve prostheses have provided important information to guide valve
      selection. The major outcome events studied include thromboembolism, hemorrhage,
      and overall survival. Both small randomized and larger retrospective studies of
      outcomes after heart valve replacement have demonstrated similar rates of
      thromboembolism with tissue and mechanical valves. Hemorrhage rates have been
      consistently higher in aortic mechanical valves. However, patients receiving
      mitral tissue valves have had similar rates of hemorrhage as those receiving
      mechanical mitral valves in one randomized trial and one large retrospective
      study suggesting that hemorrhage rates are not higher for mechanical mitral
      valves. In contrast, the published randomized and observational studies
      consistently demonstrate much higher valve failure rates in tissue valve
      recipients, regardless of valve position. Overall survival in the longest
      randomized study was better for aortic valve patients receiving a mechanical
      valve compared to those receiving a tissue valve. No survival differences have
      been observed in mitral valve patients. Analysis of age related differences in
      outcomes suggests that aortic valve patients under age 65 and mitral valve
      patients under age 70 should receive mechanical valves. These findings are
      consistent with current ACC/AHA guidelines.

PMID- 11843522
TI  - Anticoagulation management of valve replacement patients.
AB  - Anticoagulation regimens vary according to surgeon, nature of the valve
      (mechanical or biological), its position and other risk factors for stroke. The
      American College of Chest Physicians (2001) have made the following
      recommendations to protect patients with prosthetic heart valves from developing
      a stroke: (i) For mechanical heart valves: Anticoagulation with Warfarin at an
      INR range 2-3 for patients with a bileaflet mechanical valve in the aortic
      position; (ii) in the mitral position, an INR of 2.5-3.5 is recommended; an
      alternative recommendation is an INR of 2-3 in combination with aspirin (80
      mg/day); and (iii) in patients with a mechanical valve and a history of systemic
      embolization, an INR of 2.5-3.5 combined with low-dose aspirin (80-100 mg) is
      recommended; when Warfarin therapy is initiated, the doses for patients aged <70
      years is 4 mg, and for patients aged >70 years it is 3 mg. While it is important
      to recognize that the therapeutic range for Warfarin is narrow, recommendations
      have also been established to manage patients with high INRs and for the
      temporary discontinuation of anticoagulant therapy when they undergo surgical
      procedures. Rapid anticoagulation can be achieved either with unfractionated
      heparin or with low-molecular weight heparin (LMWH). Heparin is initiated with an
      intravenous bolus of 80 U/kg bodyweight, and an infusion of 18 U/kg/h. The
      activated thromboplastin time should be 60-80 s. An alternative to intravenous
      heparin is subcutaneous LMWH, which is prescribed in a mg/kg dose. In the event
      of valve thrombosis in patients who are hemodynamically unstable, surgical
      exploration with thrombectomy is indicated, with or without valve replacement. In
      patients who are hemodynamically stable, thrombolytic therapy is recommended
      initially.

PMID- 11843525
TI  - Photochemical reduction of hexavalent chromium in glycerol-containing solutions.
AB  - Hexavalent chromium [Cr(VI)] in the form of potassium dichromate was
      photochemically reduced to trivalent chromium [Cr(III)] in aqueous solutions
      containing glycerol. This reaction occurred rapidly during irradiation with
      either unfiltered sunlight or a UVA-emitting light source. Photochemical
      reduction of Cr(VI) was pH-dependent and did not occur in dilute solutions of
      sodium hydroxide. In acidified solutions, the reduction occurred at elevated
      rates and at lower concentrations of glycerol. This reaction was found to be
      dependent on the unsubstituted alcohol groups of glycerol since alpha
      phosphoglycerol and beta-phosphoglycerol did not support the photochemical
      reduction of Cr(VI). These findings suggest that glycerol or related polyols can
      be used for the remediation of hexavalent (toxic) chromium at contaminated
      environmental sites.

PMID- 11843526
TI  - Effect of fertilisation on the potassium and radiocaesium distribution in tree
      stands (Pinus sylvestris L.) and peat on a pine mire.
AB  - This paper compares the effects of single and repeated fertilisation on the
      contents of potassium, 134Cs and 137Cs in different Scots pine compartments at
      different levels above ground and in the peat profile 9 years after the Chernobyl
      disaster. The material was collected from a ditch spacing and fertilisation
      experiment in Finland. Above a needle potassium concentration of 3.0 mg g(-1) in
      composed crown samples, 137Cs and 134Cs concentrations remained at about the same
      level but below that the values were higher on average. This potassium value
      corresponded to the potassium concentrations of 3.5-3.6 mg g(-1) in the current
      year needles of two topmost whorls. The result indicates an enhanced radiocaesium
      uptake by pine trees under severe potassium deficiency. Fertilisation with
      potassium-containing fertilisers decreased the caesium uptake considerably. The
      inhibiting effect of fertilisation on caesium uptake by trees seemed to be fairly
      long lasting. Fertilisation had sped up the penetration of caesium downwards in
      the peat profile and its moving out of the active circulation of elements between
      soil and plants.

PMID- 11843527
TI  - The historical record of PAH, PCB, trace metal and fly-ash particle deposition at
      a remote lake in north-west Scotland.
AB  - Sediment cores taken from the deep basin of Loch Coire nan Arr in north-west
      Scotland were dated using 210Pb calibrated spheroidal carbonaceous particle (SCP)
      profiles and analysed for trace metals, polycyclic aromatic hydrocarbons (PAHs)
      and polychlorinated biphenyls (PCBs). These data show that the site is one of the
      least contaminated by atmospheric pollution in the UK. Peak concentrations of
      PAHs were found to be equivalent to background values at sites in the English
      Lake District. The date of concentration maxima for SCP, PCB and some metals were
      in agreement with previously published polychlorinated dibenzo-p
      dioxin/polychlorinated dibenzofuran (PCDD/F) data suggesting long-range
      industrial sources. The date of individual PAH concentration maxima were earlier,
      but concomitant with each other, possibly suggesting the influence of a local
      source. Comparison with remote European mountain lakes shows Loch Coire nan Arr
      to be one of the least contaminated sites in Europe with respect to PCBs, but
      more contaminated with respect to PAHs.

PMID- 11843528
TI  - Contaminant residues in seabird eggs from the Canadian Arctic. II. Spatial trends
      and evidence from stable isotopes for intercolony differences.
AB  - Eggs of glaucous gulls (Larus hyperboreus), black-legged kittiwakes (Rissa
      tridactyla), thick-billed murres (Uria lomvia) and black guillemots (Cepphus
      grylle) were collected from several sites throughout the Canadian Arctic. Samples
      were analyzed for organochlorines as well as mercury and selenium. Glaucous gulls
      breeding at sites in the High Arctic showed higher levels of organochlorine
      contamination than those in the western Low Arctic. This was likely due to
      dietary differences among colonies as suggested by stable isotope data, although
      different overwintering areas may also play a role. Levels of sigmaPCB, sigmaDDT,
      sigmaCHLOR, sigmaCBz and dieldrin were significantly lower in thick-billed murres
      from Prince Leopold Island in the High Arctic compared with colonies in the
      eastcrn Low Arctic. This difference was likely due to the combined effects of
      different atmospheric deposition patterns in the High and Low Arctic and
      different overwintering areas since murres from Prince Leopold Island may winter
      farther north than murres from the other colonies sampled. Eggs from colonies at
      higher latitudes generally contained higher concentrations of mercury. The
      trophic and dietary differences/similarities suggested by stable-nitrogen and
      carbon isotope data in this study were useful in explaining the spatial patterns
      of contaminant concentrations observed among colonies of seabirds such as the
      glaucous gull and the black-legged kittiwake where variation in latitudinal
      atmospheric deposition patterns and different overwintering grounds did not
      appear to be confounding factors.

PMID- 11843529
TI  - Ammonia emission, deposition and impact assessment at the field scale: a case
      study of sub-grid spatial variability.
AB  - A local ammonia (NH3) inventory for a 5x5 km area in central England was
      developed, to investigate the variability of emissions, deposition and impacts of
      NH3 at a field scale, as well as to assess the validity of the UK 5-km grid
      inventory. Input data were available for the study area for 1993 and 1996 on a
      field by field basis, allowing NH3 emissions to be calculated for each individual
      field, separately for livestock grazing, livestock housing and manure storage,
      landspreading of manures and fertiliser N application to crops and grassland. An
      existing atmospheric transport model was modified and applied to model air
      concentrations and deposition of NH3 at a fine spatial resolution (50 m grid).
      From the mapped deposition estimates and land cover information, critical loads
      and exceedances were derived. to study the implications of local variability for
      regional NH3 impacts assessments. The results show that the most extreme local
      variability in NH3 emissions, deposition and impacts is linked to housing and
      storage losses. However, landspreading of manures and intensive cattle grazing
      are other important area sources, which vary substantially in the landscape.
      Overall, the range of predicted emissions from agricultural land within the study
      area is 0-2000 kg N ha(-1) year(-1) in 1993 and 0-8000 kg N ha(-1) year(-1) in
      1996, respectively, with the peak at a poultry farm located in the study area. On
      average, the estimated field level NH3 emissions over the study area closely
      match the emission for the equivalent 5-km grid square in the national inventory
      for 1996. Deposition and expected impacts are highly spatially variable, with the
      edges of woodland and small "islands" of semi-natural vegetation in intensive
      agricultural areas being most at risk from enhanced deposition. Conversely the
      centres of larger nature reserves receive less deposition than average. As a
      consequence of this local variability it is concluded that national assessments
      at the 5 km grid level underestimate the occurrence of critical loads exceedances
      due to NH3 in agricultural landscapes.

PMID- 11843530
TI  - Biomonitoring environmental contaminants near a municipal solid-waste combustor:
      a decade later.
AB  - During the 1999 nesting season, eggs and nestlings of anhingas (Anhinga anhinga)
      and white ibises (Eudocimus albus) were collected from a colony located on the
      site of a municipal solid-waste (MSW) combustor and analyzed for residues of
      chemicals potentially released from this facility. Concentrations of most
      residues, including tetrachlorodibenzo-p-dioxin (TCDD). tetrachlorodibenzofuran
      (TCDF), arsenic, beryllium, cadmium and lead, were at levels comparable to those
      found during a similar survey done in 1989, prior to facility start-up. Nickel
      residues were detected only sporadically in anhingas and in eggs from ibises, and
      decreased significantly in concentration in ibis nestlings in 1999 compared to
      1989. While concentrations of mercury in anhinga nestlings and in eggs of both
      species were comparable to 1989 levels, its concentration was significantly
      greater in ibis nestlings in 1999. However, levels of mercury in the ibises
      remained relatively low when compared to birds from other areas of Florida and
      did not appear to represent a health threat. While lead did not increase in 1999,
      its concentration in ibis nestlings remained a concern. The most notable temporal
      trend observed in birds at this site was a general monotonic decrease in levels
      of selenium residues during the 10-year monitoring period.

PMID- 11843532
TI  - Abatement of NO3-N concentration in agricultural waters by narrow buffer strips.
AB  - The performance of narrow buffer strips in abating the NO3-N concentrations in
      the water coming from cropland was tested in an experiment carried out on the low
      plains of the Veneto Region (northeast Italy). The buffer was composed of a 5-m
      wide grass strip and a 1-m wide row of trees. Maize and wheat were cultivated in
      the neighbouring field during the monitoring period (December 1997-June 1999).
      Four experimental conditions were monitored, deriving from a combination of two
      levels of crop N fertilisation and two sizes of buffer trees. The narrow buffer
      was very effective in abating NO3-N concentrations, allowing water to be
      discharged with a concentration always below 2 ppm. Its zone of influence might
      be bigger than its simple width. The abatement was also efficient during winter.
      Tree size showed no evident effect on the reduction of the concentration.

PMID- 11843533
TI  - Cloudwater studies at a high elevation site in the Vosges Mountains (France).
AB  - Cloud and rainwater samples have been collected at a high elevation site in the
      Vosges Mountains. An automated collection system has been used to collect bulk
      cloudwater and small cloudwater droplets. Bulk cloudwater concentrations were up
      to 10 times more concentrated than rainwater concentrations. Small clouddroplets
      showed generally higher concentrations than bulk cloudwater. Nevertheless, the
      enrichment factors depend on the compounds under study and appear to be related
      to the composition of the cloud condensation nuclei forming small or large
      clouddroplets. Principal component analysis and factor analysis were applied to
      the collected datasets and confirmed the influence of the cloud condensation
      nuclei on the composition difference between small and large cloudwater droplets.

PMID- 11843534
TI  - Effects of an industrial effluent on plant colonization and on the germination
      and post-germinative growth of seeds of terrestrial and aquatic plant species.
AB  - Major oil sands industrial companies are located in the Athabasca Oil Sands
      Deposit in northeastern Alberta, Canada. During the process used to extract light
      crude oil (via hot water digestion and flotation), gypsum is usually added to
      produce consolidated tails (CT) and CT release water. The vast volumes of process
      treated waters (effluent) are held within large dyked tailings ponds. Toward
      testing viable options for reclamation, various hummock-wetlands systems have
      been constructed; in addition, natural wetlands (inhabited by obligate wetland
      plant species) have become established as a result of seeping of the effluents
      held within the large dyked ponds. Vegetation surveys conducted on and around the
      industrial site revealed that the constructed wetlands associated with the dyke
      drainage (effluent treated with phosphorous) and consolidated tails (CT; effluent
      treated with gypsum) had low biodiversity and were not invaded by many aquatic
      plants. Although the natural wetland was also not invaded by many aquatic
      species, it was found to be as diverse as the reference wetlands (i.e. off-site
      wetlands not exposed to the effluents). Exposure to oil sands effluents had an
      inhibitory effect on the germination (percent and/or rate) of several plant
      species (tomato, clover, wheat, rye, pea, reed canary grass, loblolly pine);
      clover and tomato seed germination were most affected. Two treatments in
      particular (effluents from the natural on-site wetland and the CT constructed
      wetland), delayed germination, and also led to reduced fresh weight of seedlings
      of tomato, wheat, clover and loblolly pine. The osmolarities of the effluents
      associated with the natural on-site wetland and CT constructed wetland were 712
      and 728 mOs/kg, respectively; substituting these effluents with solutions of
      polyethylene glycol of the same osmotic potentials had a greater inhibitory
      effect on germination rate. The negative effects of the effluents on seed
      germination may account for the paucity of aquatic species that invaded the oil
      sands impacted wetlands. This factor will also be critical in determining the
      long-term feasibility of hummock-wetland systems.

PMID- 11843531
TI  - Pyrene degradation by yeasts and filamentous fungi.
AB  - The saprotrophic soil fungi Fusarium solani (Mart.) Sacc., Cylindrocarpon didymum
      (Hartig) Wollenw, Penicillium variabile Sopp. and the yeasts Rhodotorula glutinis
      (Fresenius) Harrison and Rhodotorula minuta (Saito) Harrison were cultured in
      mineral medium with pyrene. The remaining pyrene concentrations were periodically
      determined during 20 incubation days, using HPLC. To assess the metabolism of
      pyrene degradation we added 0.1 microCi of [4,5,9,10] 14C-pyrene to each fungi
      culture and measured the radioactivity in the volatile organic substances,
      extractable, aqueous phase, biomass and 14CO2 fractions. The assays demonstrated
      that F. solani and R. glutinis metabolized pyrene as a sole source of carbon.
      Differences in their activities at the beginning of the cultures disappeared by
      the end of the experiment, when 32 and 37% of the original pyrene concentration
      was detected, for the soil fungi and yeasts, respectively. Among the filamentous
      fungi, F. solani was highly active and oxidized pyrene; moreover, small but
      significant degradation rates were observed in C. didymum and P. variahile
      cultures. An increase in the 14CO2 evolution was observed at the 17th day with
      cosubstrate. R. glutinis and R. minuta cultures showed similar ability to
      biotransform pyrene, and that 35% of the initial concentration was consumed at
      the end of the assay. The same results were obtained in the experiments with or
      without glucose as cosubstrate.

PMID- 11843535
TI  - Trace gas emissions from German agriculture as obtained from the application of
      simpler or default methodologies.
AB  - For the assessment of emission inventories matching pairs of activities (emission
      explaining variables) and emission factors are used. Simpler and detailed
      methodologies are proposed within the emission inventory handbooks. The data sets
      needed to serve the detailed methodologies have not been at public disposal so
      far. Therefore, this paper investigates the applicability of simpler
      methodologies to the statistical data sets of activities officially available in
      Germany. The statistical data base for the assessment of emissions from
      fertilised soils is adequate if one assumes that fertilisers sold in one
      financial year are applied in the same year. For grassland, statistical data
      describing the actual management do not exist. Lack of nitrogen inputs with crop
      residues and due to nitrogen fixation make it impossible to deduce the respective
      emissions. The assessment of indirect emissions due to reactions of leached
      nitrogen is also impossible. For extensively managed grasslands, data concerning
      fertiliser application or grazing are missing when calculating emissions. The
      determination of emissions from organic soils presupposes the knowledge of both
      the area concerned and the degree of mineralisation which has been attained at
      the time of the inventory. The results of the biennial animal census meet the
      requirements of the simpler methodologies. However, the assumptions made to
      evaluate the mean emission factors are not correct in many cases, as far as
      animal performance, housing, storage and application of animal excreta are
      concerned. The simpler methodologies are biassed, as the emission factors are
      (Northwest) European means. Changes in the raising of statistical data make the
      construction of meaningful time-series difficult.

PMID- 11843536
TI  - Seasonal variability of mercury and heavy metals in roe deer (Capreolus
      capreolus) kidney.
AB  - The seasonal variability of Hg, Pb, Cd and Zn was determined in the kidney of 164
      roe deer, shot in three areas of Slovenia in 1998. We found a strong seasonal
      influence on Hg and Pb levels, which were significantly higher in late summer and
      early autumn. Cd and Zn levels showed a similar seasonal pattern, although not so
      pronounced; for these elements differences among periods were probably not a
      consequence of season per se. Seasonal variability in metal levels in roe deer
      kidney originated in both quantitative and qualitative differences in nutrition
      of the species. Since the seasonal peaks for the majority of metals appeared in a
      very narrow summer autumnal period (August-September), it seems that some plant
      taxons, such as fungi, might represent an important pathway for heavy metal
      intake into the mammalian organism. The season of sample collection has to be
      considered whenever using wildlife as an accumulative bioindicator of
      environmental pollution. Moreover, the influence of the season should be born in
      mind whenever a hazard due to accumulation of heavy metals along the food chain
      is assessed.

PMID- 11843537
TI  - Influence of diet and sea ice drift on organochlorine bioaccumulation in Arctic
      ice-associated amphipods.
AB  - The drifting sea ice has been suggested as important in the transport and
      concentration of organic matter and pollutants in the Arctic. We collected sea
      ice-associated amphipods in the marginal ice zone north of Svalbard and in the
      Fram Strait in September 1998 and 1999 to assess contaminant accumulation in ice
      associated organisms. Organochlorine concentrations increased from the more
      herbivorous Apherusa glacialis to the more carnivorous Gammarus wilkitzkii and
      the more necrophagous Onisimus spp. The relative contribution of compound classes
      to the sum of organochlorines differed between the amphipod families, with a
      higher relative contribution of hexachlorocyclohexanes (HCHs) in A. glacialis.
      The composition of the compound classes HCHs. chlordanes and
      dichlorodiphenyltrichloroethanes (DDTs) was similar between the amphipod
      families, whereas the profiles of polychlorinated biphenyls (PCBs) differed. The
      occurrence of organochlorines differed spatially, with higher alpha-HCH
      concentrations in amphipods from the Fram Strait in comparison with amphipods
      collected north of Svalbard. This could be related to the sea ice drift route,
      since sea ice in the Fram Strait had a drift route across the central Arctic
      Ocean, while the sea ice north of Svalbard had a western drift route to the
      sampling stations. Even though marine invertebrates have direct uptake by passive
      diffusion of contaminants across their gills. our results imply that the species'
      ecology such as diet is important in the bioaccumulation process of organic
      pollutants. In addition, the results show that sea ice drift route influences the
      concentrations of organochlorine pollutants in ice-associated organisms.

PMID- 11843538
TI  - Uptake and translocation of plutonium in two plant species using hydroponics.
AB  - This study presents determinations of the uptake and translocation of Pu in
      Indian mustard (Brassica juncea) and sunflower (Helianthus annuus) from Pu
      contaminated solution media. The initial activity levels of Pu were 18.50 and
      37.00 Bq ml(-1), for Pu-nitrate [239Pu(NO3)4] and for Pu-citrate [239Pu(C6H5O7)+]
      in nutrient solution. Plutonium-diethylenetriaminepentaacetic acid (DTPA: [239Pu
      C14H23O10N3] solution was prepared by adding 0, 5, 10, and 50 microg of DTPA ml(
      1) with 239Pu(NO3)4 in nutrient solution. Concentration ratios (CR, Pu
      concentration in dry plant material/Pu concentration in nutrient solution) and
      transport indices (Tl, Pu content in the shoot/Pu content in the whole plant)
      were calculated to evaluate Pu uptake and translocation. All experiments were
      conducted in hydroponic solution in an environmental growth chamber. Plutonium
      concentration in the plant tissue was increased with increased Pu contamination.
      Plant tissue Pu concentration for Pu-nitrate and Pu-citrate application was not
      correlated and may be dependent on plant species. For plants receiving Pu-DTPA,
      the Pu concentration was increased in the shoots but decreased in the roots
      resulting in a negative correlation between the Pu concentrations in the plant
      shoots and roots. The Pu concentration in shoots of Indian mustard was increased
      for application rates up to 10 microg DTPA ml(-1) and up to 5 microg DTPA ml(-1)
      for sunflower. Similar trends were observed for the CR of plants compared to the
      Pu concentration in the shoots and roots, whereas the Tl was increased with
      increasing DTPA concentration. Plutonium in shoots of Indian mustard was up to 10
      times higher than that in shoots of sunflower. The Pu concentration in the
      apparent free space (AFS) of plant root tissue of sunflower was more affected by
      concentration of DTPA than that of Indian mustard.

PMID- 11843539
TI  - Winter indoor air pollution in Alaska: identifying a myth.
AB  - The benzene and toluene levels inside three homes with attached garages were
      measured for 12 consecutive weeks during the winter months in Fairbanks, Alaska
      (Latitude 64.5 degrees N). Results for air samples collected over 12 h for the
      homes showed indoor benzene mixing ratios ranging from 1.6 to 20.4 parts per
      billion of mixing ratio volume (ppbv), and toluene air mixing ratios ranging from
      7.3 to 41.6 ppbv. A correlation between benzene and toluene levels in each home
      and similar regression lines suggested the same major emission source, car and
      small equipment gasoline, present in attached garages. In one home, there was a
      correlation between indoor benzene mixing ratios and the urinary biomarker,
      trans,trans-muconic acid. Inside, air mixing ratios of benzene and toluene
      decreased with decreasing outside temperature in all homes studied, even though
      homes were relatively tight to prevent heat loss during this period of low winter
      outdoor temperatures. It is suggested that buildup of these pollutants indoors is
      prevented by the influence of an increased indoor/outdoor temperature
      differential and an ensuing increase in home ventilation.

PMID- 11843540
TI  - Biomonitoring of heavy metals and air quality in Cordoba City, Argentina, using
      transplanted lichens.
AB  - The objective of the present study was to test the concentrations of some
      elements in the transplanted lichen Usnea amblyoclada transplanted in Cordoba,
      Argentina, and to investigate the relative air quality of the area as indicated
      by a Pollution Index. Analyses of Cu, Co. Pb, Fe, Ni, Mn, S and Zn in addition to
      analyses of physiological parameters were performed after the transplantation
      period. No significant differences were observed among the sampling stations for
      the physiological parameters, except the dry weight/fresh weight ratio. The
      concentration of most elements was similar to or lower than those found in non
      polluted and even polluted areas. The significant correlation found between Cu,
      Pb and Zn with the content of hydroperoxy conjugated dienes suggests an important
      oxidative effect probably caused by these ions. The distribution patterns of the
      elements were quite similar, with maximum values around a cement plant and the
      metallurgical industries. The Pollution Index distribution pattern does not
      coincide with the elements distribution, due to the fact that the index values
      probably reflected the emissions of gaseous phytotoxic pollutants.

PMID- 11843541
TI  - Multi-generation toxicity of zinc, cadmium, copper and lead to the potworm
      Enchytraeus albidus.
AB  - In standard chronic terrestrial toxicity tests with invertebrates, adult
      organisms are exposed to the contaminants and the number of offspring is
      quantified. These procedures do not allow the assessment of possible effects on
      all life stages of the organism, which may lead to an underestimation of the
      toxicity of the test substance. To evaluate the importance of this issue, the
      potworm Enchytraeus albidus was exposed to zinc, cadmium, copper and lead for two
      subsequent generations. Juvenile production was assessed for both generations.
      Considering the variability of metal toxicity data reported in the literature, it
      is concluded that the two generation assay did not markedly increase the
      sensitivity of the standard E. albidus test for the tested metals. Therefore,
      toxicity data obtained with the proposed test guideline with E. albidus are
      protective for all life stages.

PMID- 11843542
TI  - Trace analysis of dissolved polychlorinated organic compounds in the water of the
      Yangtse River (Nanjing, China).
AB  - Eighteen organochlorine contaminants from the water samples of the Yangtse River
      have been qualitatively and quantitatively analyzed. The analysis of
      polychlorinated organic compounds (PCOCs) extracted by C18 Solid Phase Extract
      (SPE) was performed using HP6890 gas chromatograph coupled by ECD detector. The
      analytical results demonstrate that the analytical methods are reliable based on
      the fact that most of the recoveries for the targeted compounds are 60-90%. Most
      of the concerned contaminants, i.e. chlorinated pesticides and PCBs were found in
      the water samples of the Yangtse River, but their concentration was very low,
      <2.97 ng l(-1), which is far less than 1 microg l(-1)--the standard of drinking
      water of China. It is apparent that the PCOCs were in high concentration during
      the dry season, and in low concentration during the rainy season. The situation
      of PCOCs contamination in the water of the Yangtse River in 1999 was greatly
      improved in comparison with 10 years ago.

PMID- 11843543
TI  - An evaluation of ozone exposure metrics for a seasonally drought-stressed
      ponderosa pine ecosystem.
AB  - Ozone stress has become an increasingly significant factor in cases of forest
      decline reported throughout the world. Current metrics to estimate ozone exposure
      for forest trees are derived from atmospheric concentrations and assume that the
      forest is physiologically active at all times of the growing season. This may be
      inaccurate in regions with a Mediterranean climate, such as California and the
      Pacific Northwest, where peak physiological activity occurs early in the season
      to take advantage of high soil moisture and does not correspond to peak ozone
      concentrations. It may also misrepresent ecosystems experiencing non-average
      climate conditions such as drought years. We compared direct measurements of
      ozone flux into a ponderosa pine canopy with a suite of the most common ozone
      exposure metrics to determine which best correlated with actual ozone uptake by
      the forest. Of the metrics we assessed, SUM0 (the sum of all daytime ozone
      concentrations > 0) best corresponded to ozone uptake by ponderosa pine, however
      the correlation was only strong at times when the stomata were unconstrained by
      site moisture conditions. In the early growing season (May and June). SUM0 was an
      adequate metric for forest ozone exposure. Later in the season, when stomatal
      conductance was limited by drought. SUM0 overestimated ozone uptake. A better
      metric for seasonally drought-stressed forests would be one that incorporates
      forest physiological activity, either through mechanistic modeling, by weighting
      ozone concentrations by stomatal conductance, or by weighting concentrations by
      site moisture conditions.

PMID- 11843544
TI  - Cultural psychology, A new look: reply to Bond (2002), Fiske (2002), Kitayama
      (2002), and Miller (2002).
AB  - M. H. Bond (2002), A. P. Fiske (2002), S. Kitayama (2002), and J. G. Miller
      (2002) joined D. Oyserman, H. M. Coon, and M. Kemmelmeier (2002) in highlighting
      limitations of the individualism-collectivism model of culture. Concern is
      warranted; nevertheless, individualism-collectivism helps structure discourse on
      the influence of culture on the mind. To avoid level-of-analysis entanglements,
      Oyserman et al. propose an integrative model that includes distal, proximal, and
      situated cultural features of societies and internalized models of these
      features, highlights the importance of subjective construal, and uses
      evolutionary perspectives to clarify the basic problems cultures address. Framed
      this way, it is clear that, depending on situational requirements, both
      individualism- and collectivism-focused strategies are adaptive; thus, it is
      likely that human minds have adapted to think both ways.

PMID- 11843545
TI  - A meta-analytic examination of comorbid hyperactive-impulsive-attention problems
      and conduct problems.
AB  - The author quantitatively reviewed prevalence rates, defining features,
      associated features, developmental trajectory, and etiology to examine 3
      taxonomic questions about comorbid hyperactive-impulsive-attention problems (HIA)
      and conduct problems (CP): Do HIA and CP co-occur randomly? Does comorbid HIA-CP
      differ from HIA-only and CP-only? Do HIA and CP combine synergistically? Results
      showed that HIA and CP co-occur at a greater than random rate, that comorbid HIA
      CP differs from HIA-only and CP-only in multiple ways, and that there is little
      evidence that HIA and CP combine synergistically. However, sample type, grouping
      definition, age, gender, and subtype of disruptive behavior often moderated these
      findings. Overall, the review suggests that HIA-CP is best conceptualized as an
      additive combination of HIA and CP rather than as a distinct category.

PMID- 11843546
TI  - Older age, traumatic brain injury, and cognitive slowing: some convergent and
      divergent findings.
AB  - Reaction time (RT) meta-analyses of cognitive slowing indicate that all stages of
      processing slow equivalently and task independently among both older adults (J.
      Cerella & S. Hale, 1994) and adults who have suffered a traumatic brain injury
      (TBI; F. R. Ferraro, 1996). However, meta-analyses using both RT and P300 latency
      have revealed stage-specific and task-dependent changes among older individuals
      (T. R. Bashore, K. R. Ridderinkhof, & M. W. van der Molen, 1998). Presented in
      this article are a meta-analysis of the effect of TBI on processing speed,
      assessed using P300 latency and RT, and a qualitative review of the literature.
      They suggest that TBI induces differential slowing. Similarities in the effects
      of older age and TBI on processing speed are discussed and suggestions for future
      research on TBI-induced cognitive slowing are offered.

PMID- 11843547
TI  - Rethinking individualism and collectivism: evaluation of theoretical assumptions
      and meta-analyses.
AB  - Are Americans more individualistic and less collectivistic than members of other
      groups? The authors summarize plausible psychological implications of
      individualism-collectivism (IND-COL), meta-analyze cross-national and within
      United States IND-COL differences, and review evidence for effects of IND-COL on
      self-concept, well-being, cognition, and relationality. European Americans were
      found to be both more individualistic-valuing personal independence more-and less
      collectivistic-feeling duty to in-groups less-than others. However, European
      Americans were not more individualistic than African Americans, or Latinos, and
      not less collectivistic than Japanese or Koreans. Among Asians, only Chinese
      showed large effects, being both less individualistic and more collectivistic.
      Moderate IND-COL effects were found on self-concept and relationality, and large
      effects were found on attribution and cognitive style.

PMID- 11843548
TI  - Reclaiming the individual from Hofstede's ecological analysis--a 20-year odyssey:
      comment on Oyserman et al. (2002).
AB  - D. Oyserman, H. M. Coon, and M. Kemmelmeier (2002) challenge the stereotype that
      European Americans are more individualistic and less collectivistic than persons
      from most other ethnic groups. The author contends that this stereotype took firm
      empirical root with G. Hofstede's (1980) monumental publication identifying the
      United States as the most individualistic of his then 40 nations. This empirical
      designation arose because of challengeable decisions Hofstede made about the
      analysis of his data and the labeling of his dimensions. The conflation of
      concepts under the rubric of cultural individualism plus psychologists'
      unwarranted psychologizing of the construct then combined with Hofstede's
      empirical location of America to set a 20-year agenda for data collection.
      Oyserman et al. disentangle and organize this mass of studies, enabling the
      discipline of cross-cultural psychology to forge ahead in more productive
      directions, less reliant on previous assumptions and measures.

PMID- 11843549
TI  - Using individualism and collectivism to compare cultures--a critique of the
      validity and measurement of the constructs: comment on Oyserman et al. (2002).
AB  - Analyzing national and ethnic differences in individualism and collectivism, D.
      Oyserman, H. M. Coon, and M. Kemmelmeier (2002) showed that small differences in
      scales or samples produce markedly divergent results, challenging the validity of
      these constructs. The author examines the following limitations of research on
      individualism and collectivism: It treats nations as cultures and culture as a
      continuous quantitative variable; conflates all kinds of social relations and
      distinct types of autonomy; ignores contextual specificity in norms and values;
      measures culture as the personal preferences and behavior reports of individuals;
      rarely establishes the external validity of the measures used; assumes cultural
      invariance in the meaning of self-reports and anchoring and interpretation of
      scales; and reduces culture to explicit, abstract verbal knowledge.

PMID- 11843550
TI  - Culture and basic psychological processes--toward a system view of culture:
      comment on Oyserman et al. (2002).
AB  - D. Oyserman, H. M. Coon, and M. Kemmelmeier (2002) provide a most comprehensive
      review of empirical studies that used attitudinal surveys to capture cultural
      variations in individualism and collectivism. In the present article, the author
      suggests that the cross-cultural validity of attitudinal surveys can no longer be
      taken for granted. Moreover, the meta-theory underlying this literature (called
      the entity view of culture) is called into question. The author presents an
      alternative meta-theory (called the system view of culture) and discusses its
      implications for future work in cultural and cross-cultural psychology.

PMID- 11843551
TI  - Bringing culture to basic psychological theory--beyond individualism and
      collectivism: comment on Oyserman et al. (2002).
AB  - D. Oyserman, H. M. Coon, and M. Kemmelmeir (2002) offered a comprehensive
      literature review on individualism and collectivism that forwards valuable
      suggestions for ways to enhance future research conducted within this framework.
      The author argues that although their criticisms of much contemporary social
      psychological research on individualism and collectivism are valid, even more
      fundamental problems need to be recognized as characterizing work within this
      tradition, such as the insufficiently subtle nature of the views held of culture,
      the limited attention given to meanings, and the downplaying of contextual
      variation. The author suggests adopting more nuanced and process-oriented
      conceptions of culture and more contextually grounded views of its impact on
      psychological functioning as a way of realizing the promise of cultural
      psychology to broaden and provide insight into basic psychological theory.

PMID- 11843552
TI  - In Romania it's the Methode Babes-Papanicolaou.

PMID- 11843554
TI  - Procedure for immunocytochemical detection of P16INK4A antigen in thin-layer,
      liquid-based specimens.
AB  - OBJECTIVE: To develop a procedure for the immunocytochemical detection of
      P16INK4A in ThinPrep specimens. STUDY DESIGN: Archived ThinPrep, liquid-based
      cervical/endocervical cytology specimens (Cytyc Corp., Boxborough, Massachusetts,
      U.S.A.) diagnosed as LSIL, HSIL and WNL were resampled and fixed in 95% ethanol
      for at least three days. Rehydration and endogenous peroxidase blocking of both
      ThinPreps and formalin-fixed, paraffin-embedded tissues were accomplished on a
      Leica Autostainer (Leica, Deerfield, Illinois, U.S.A.). Microwave antigen
      retrieval with CitraPlus (Biogenex, San Ramon, California, U.S.A.) was performed
      using a Panasonic microwave oven (Matsushita Cooking Appliances, Franklin Park,
      Illinois, U.S.A.) on the high setting twice for five minutes each. After cooling
      for 20 minutes and undergoing a buffer rinse, the slides were placed in a Dako
      autostainer (Dako-USA, Carpinteria, California, U.S.A.). The P16INK4A primary
      antibody, clone E6H4 (MTM Laboratories, Heidelberg, Germany) was diluted 1:200 in
      antibody diluent buffer. Detection was accomplished with a mouse non-avidin
      biotin EnVision+ polymer (Dako). The expression of P16INK4A in ThinPreps and
      corresponding biopsies were scored by two pathologists. A ThinPrep case was
      scored as positive if it contained > 10 abnormal cells with nuclear and
      cytoplasmic immunocytochemical staining. Corresponding biopsies were scored as
      exhibiting negative, sporadic, focal or diffuse staining, as described by Klaes
      et al, Overexpression of P16INK4A as specific marker for dysplastic and
      neoplastic epithelial cells of the cervix uteri (Int J Cancer 2001;92:276-284).
      RESULTS: The P16INK4A antibody assay was positive in 14 of 19 (73.68%) LSIL
      ThinPrep cases and in 25 of 26 (96.15%) HSIL ThinPrep cases. Thirty-eight of the
      39 (97.44%) biopsies corresponding to the positively stained ThinPreps also were
      positive, with a staining score of at least focal positivity in the dysplastic
      regions. The P16INK4A antibody assay was negative in 5 of 19 (26.32%) LSIL
      ThinPrep cases and negative in 1 of 26 (3.85%) HSIL ThinPrep cases. The six
      biopsies corresponding to the negative ThinPreps were similarly negative. The two
      cytologic specimens diagnosed as WNL were negative for P16INK4A, as were two
      tissue control cases with benign diagnoses. Nondysplastic squamous epithelium,
      identified in 17 biopsy cases, did not stain, nor did nondysplastic squamous
      cells identified in ThinPrep cases. Sporadic staining of bacteria, inflammatory
      cells and occasional endocervical glandular cells was identified. CONCLUSION:
      P16INK4A expression in ThinPrep specimens correlates with tissue expression of
      P16INK4A, as implemented in the above protocol. P16INK4A may thus serve as a
      surrogate marker in gynecologic cytology for high-risk HPV infection and for the
      development of cervical neoplasia.

PMID- 11843553
TI  - Melanoma metastatic to the breast: utility of fine needle aspiration and
      immunohistochemistry.
AB  - OBJECTIVE: To describe the morphologic spectrum of metastatic malignant melanoma
      (MM) cells involving the breast and to explore the diagnostic utility of HMB45,
      Mart-1, Melan-A and T311 (antityrosinase) antibodies in fine needle aspiration
      material of MM metastatic to the breast. STUDY DESIGN: Cytologic material from 21
      cases (18 women) was reviewed for cytomorphology (epithelioid, spindled, mixed)
      and immunocytochemical staining attributes for Mart-1, HMB45, T311, Melan-A and
      cytokeratin based on tissue availability. RESULTS: Seventeen cases (81%)
      demonstrated epithelioid cell morphology, with 14% exhibiting mixed and 5%
      spindled morphologies. All 21 cases (100%) were immunoreactive with Mart-1
      antibody, with 81% (17/21) immunoreactive for HMB45. In 38% of cases there was a
      similar percentage of cells immunoreactive for Mart-1 and HMB45, while 48% showed
      a higher percentage of cells immunoreactive for MART-1 than HMB45.
      Immunoreactivity with T311 was seen in 8 of 11 cases tested (73%). All six cases
      tested (100%) were immunoreactive with Melan-A. Staining for cytokeratin was
      negative in all eight cases tested. CONCLUSION: Because the majority of MM
      metastatic to the breast shows epithelioid cell morphology, it may mimic primary
      breast carcinoma. Mart-1 should be part of the immunocytochemical panel utilized
      to confirm the diagnosis of MM metastatic to the breast.

PMID- 11843555
TI  - Comparative study of fine needle aspiration and fine needle capillary sampling of
      thyroid lesions.
AB  - OBJECTIVE: To investigate whether fine needle capillary (FNC) sampling gives
      quantitatively and qualitatively superior cytologic material as compared to the
      conventional technique of fine needle aspiration (FNA) when performed by a single
      aspirator. STUDY DESIGN: Cross-sectional diagnostic test evaluation study. FNA
      and FNC were performed by a single operator on 200 diffuse and nodular thyroid
      lesions. RESULTS: A statistically significant difference in favor of FNC was
      observed for the parameter amount of cellular material. For the rest of the
      parameters--background blood or clot, degree of cellular degeneration, degree of
      cellular trauma and retention of architecture--the average score favored FNC but
      was not statistically significant--i.e., smears prepared from FNC displayed
      cellular material that was more concentrated, less damaged and less likely to be
      obscured by blood. CONCLUSION: Although FNC sampling was diagnostic in a greater
      number of cases than FNA sampling, this study did not prove a clear superiority
      of FNC over FNA. Until greater experience shows clear sampling superiority of FNC
      alone, rather than performing only FNA in diffuse or nodular thyroid lesions,
      incorporating FNC into the second puncture will definitely improve the quality
      and quantity of material at the patient's first visit.

PMID- 11843557
TI  - Fine needle aspiration cytology of metastatic olfactory neuroblastoma: a case
      report.
AB  - BACKGROUND: Olfactory neuroblastoma (ONB) is an uncommon tumor, presenting as a
      polypoid mass arising from the upper nasal cavity. This tumor has been seldom
      diagnosed by direct fine needle aspiration (FNA). CASE: Metastatic ONB was
      diagnosed by FNA. The patient was a 40-year-old female with a polypoid mass in
      the nasal cavity and ipsilateral cervical lymphadenopathy. The punch biopsy of
      the nasal tumor revealed a smudged small round cell neoplasm with neuroendocrine
      differentiation, consistent with ONB. In FNA smears from the cervical lymph node,
      there were well-preserved, small, monotonous cells with hyperchromatic nuclei,
      fibrillary cytoplasm and indistinct cell borders. Also noteworthy were occasional
      pseudorosettes as well as rare true rosettes. By immunocytochemistry, tumor cells
      were positive for cytokeratin, chromogranin and synaptophysin. CONCLUSION: ONB,
      like adrenal neuroblastoma, shows distinctive cytologic features, including a
      rosette or pseudorosette and fibrillary network. FNA can accurately demonstrate
      these characteristic findings, and in some cases it may be a better diagnostic
      modality than incisional biopsy.

PMID- 11843556
TI  - Fine needle aspiration diagnosis in HIV-related lymphadenopathy in Mangalore,
      India.
AB  - OBJECTIVE: To evaluate the usefulness of fine needle aspiration (FNA) study of
      lymph nodes in HIV-positive patients. STUDY DESIGN: The study was conducted at
      Kasturba Medical College, Mangalore, India. Samples from lymph nodes of 48 HIV
      positive patients were taken and air dried, and wet smears were made. After
      staining with routine cytologic stains and special stains, detailed
      cytomorphologic study was conducted. RESULTS: Tuberculosis accounted for nearly
      half (48%) the cases,followed by HIV lymphadenitis (36%), lymphoma (10%),
      suppurative lymphadenitis (2%), Mycobacterium avium-intracellulare lymphadenitis
      (2%) and metastases (2%), in descending order of their frequency. A suppurative
      picture, which was found in 13% of cases of tuberculous lymphadenitis in AIDS
      patients, occasionally was misleading without the help of acid fast bacilli
      stain. CONCLUSION: FNA is a useful tool in the diagnosis of lymphadenopathy in
      HIV-positive patients provided that proper safety measures are taken to avoid
      contracting the infection.

PMID- 11843558
TI  - Diagnosis of calcium pyrophosphate dihydrate deposition disease by fine needle
      aspiration biopsy: a case report.
AB  - BACKGROUND: Calcium pyrophosphate dihydrate deposition disease is a relatively
      rare disease with variable clinical presentations. CASE: A 73-year-old man
      presented with worsening lower back pain and fever. Fine needle aspiration biopsy
      of the lumbar vertebral bodies (L3-L4) revealed abundant neutrophils admixed with
      small, birefringent, rhomboid crystals in Diff-Quik-stained smears. These
      crystals were confirmed as calcium pyrophosphate dihydrate on cell block
      sections. A diagnosis of osteomyelitis and calcium pyrophosphate dihydrate
      deposition disease was rendered. The patient was treated with antibiotics and
      responded well. CONCLUSION: Calcium pyrophosphate dihydrate deposition disease
      can be diagnosed by fine needle aspiration biopsy, and an accurate diagnosis can
      be greatly facilitated by cell block sections. However, such a diagnosis may be
      neglected if the specimen is not carefully inspected.

PMID- 11843559
TI  - Malignant phyllodes tumor with pleomorphic liposarcomatous stroma diagnosed by
      fine needle aspiration cytology: a case report.
AB  - BACKGROUND: Liposarcomatous differentiation within a phyllodes tumor is extremely
      rare. Cytologic and histologic findings of a case of malignant phyllodes tumor
      with liposarcomatous stroma of the breast are presented. CASE: A 45-year-old
      female had a malignant phyllodes tumor with pleomorphic liposarcomatous stroma
      diagnosed by fine needle aspiration (FNA) cytology. The cytologic findings were
      representative of the histologic features. CONCLUSION: Malignant phyllodes tumor
      of the breast can be diagnosed by FNA. It is very important to acknowledge the
      morphologic variants of sarcomatous stroma and to recognize the cytologic
      features of such rare tumors to prevent misdiagnosis as primary sarcomas of the
      breast. Preoperative diagnosis is important in planning the most appropriate type
      of treatment. It is also important to follow patients for long periods for
      recurrence and metastasis after surgery for this tumor.

PMID- 11843560
TI  - Intranuclear inclusions in fine needle aspirates of bronchial low grade
      mucoepidermoid carcinoma with clear cell change: a report of two cases.
AB  - BACKGROUND: Mucoepidermoid carcinoma of the bronchus is a rare neoplasm that can
      be recognized on histology as well as cytology by the presence of three
      characteristic cell types: mucus secreting, epidermoid and intermediate. We
      encountered two cases displaying unusual cytologic features, including clear
      intranuclear inclusions. CASES: Two females, aged 33 and 39, presented with an
      intrabronchial tumor and pulmonary parenchymatous mass, respectively. Fine needle
      aspiration of both tumors showed similar cytologic features, with a dominant
      population of cells with bland nuclei and wide cytoplasm, and frequent
      intranuclear inclusions. A minor component of mucus-secreting cells was also
      recognized. Histologically, both tumors corresponded to the clear cell variant of
      mucoepidermoid carcinoma. CONCLUSION: The cytologic picture in our cases has not
      been described previously in fine needle aspirates of mucoepidermoid carcinoma,
      in neither the bronchus nor salivary gland. The differential diagnosis of a
      monotonous population of epithelial cells with intranuclear inclusions involves
      bronchioloalveolar carcinoma, but the absence of the characteristic sheet
      pattern, as well as the clinical and image findings, excludes this possibility.
      The lack of atypia and intrabronchial location limits the scope to carcinoid and
      salivary gland-type tumors of the bronchus. Since we were aware of the
      possibility of unusual cytologic presentations of mucoepidermoid carcinomas,
      search for different cellular populations suggested the precise diagnosis.

PMID- 11843561
TI  - Ascitic fluid and imprint cytology of mixed germ cell tumor of the ovary.

PMID- 11843562
TI  - Microglandular hyperplasia-adenocarcinoma.

PMID- 11843563
TI  - ASCUS in postmenopausal women.

PMID- 11843564
TI  - Association of microfilariae with leprosy and other diseases.

PMID- 11843565
TI  - Microfilariae in esophageal stricture.

PMID- 11843566
TI  - Signet-ring cell cytology in ovarian clear cell carcinoma.

PMID- 11843567
TI  - Microfilariae in lymph node aspirates.

PMID- 11843568
TI  - Unusual presentation of disseminated echinococcosis with thyroid involvement:
      diagnosis by fine needle aspiration cytology in a clinically unsuspected case.

PMID- 11843569
TI  - Influence of ground-state conformations on the intramolecular amidofuran Diels
      Alder reaction.
AB  - [reaction: see text] Various factors that influence the rate of the
      intramolecular Diels-Alder reaction of amidofurans were investigated with density
      functional theory calculations using the Becke3LYP/6-31G* model. Conformational
      effects imposed by the placement of a carbonyl group within the tether, combined
      with a rotational bias about the C(2)-N bond, account for the observed rate
      differences in the thermal chemistry of these amidofurans.

PMID- 11843570
TI  - Molecular color sensors for monosaccharides.
AB  - [structure: see text] Boronic acid color sensor 2 undergoes a visible color
      change, from purple to pink, on the addition of monosaccharides in aqueous
      methanol at pH 8.21.

PMID- 11843571
TI  - Synthesis of the C1-C21 (C1'-C21') fragment of the dimeric polyketide natural
      product SCH 351448.
AB  - [structure: see text] A convergent, stereoselective assembly of the C1-C21 (C1'
      C21') fragment of SCH 351448, a 28-membered bis-lactone natural product, has been
      developed. A highly efficient approach to this fragment assembles 75% of the
      carbon skeleton and all the stereochemical elements present in the natural
      product. In addition, an interesting boron ligand effect on the
      diastereoselectivity of a key aldol reaction with methyl ketone-derived
      enolborinates is reported.

PMID- 11843572
TI  - Synthetic studies toward bioactive cyclic peroxides from the marine sponge
      Plakortis angulospiculatus.
AB  - [reaction: see text] The total synthesis of two stereoisomers of a bioactive
      cyclic peroxide isolated from the marine sponge Plakortis angulospiculatus has
      been achieved in 18 steps with an overall yield of 2.8%. Diels-Alder addition of
      singlet oxygen to an acyclic triene carboxylic acid precursor was used to
      construct the 3,6-dihydro-1,2-dioxin ring. By comparing spectral data of the
      synthesized compounds and the natural material, we tentatively assign the
      absolute stereochemistry for the natural product as 3S,6R,8S,10R.

PMID- 11843573
TI  - Stereospecific entry to [4.5]spiroketal glycosides using alkylidenecarbene C-H
      insertion.
AB  - [reaction: see text] A novel method for the stereospecific preparation of
      [4.5]spiroketal glycosides utilizing the 1,5 C-H bond insertion of
      alkylidenecarbenes is described. Treatment of 2-oxopropyl beta-pyranosides A with
      lithium (trimethylsilyl)diazomethane in THF at -78 degrees C afforded 1,6
      dioxaspiro[4,5]decenes B in good yield. Submission of the corresponding alpha
      glycosides C to the same reagent gave the isomeric insertion products D in
      moderate to high yield.

PMID- 11843574
TI  - Reactive dienes: intramolecular aromatic oxidation of 3-(2-hydroxyphenyl)
      propionic acids.
AB  - [reaction: see text] Treatment of 3-(2-hydroxyphenyl)-propionic acids with a
      hypervalent iodine reagent in the presence of a dienophile initiates a tandem
      intramolecular aromatic oxidation/Diels-Alder reaction. Herein we report (1)
      investigations on the scope and limitations of this novel reaction combination
      and (2) preliminary diastereoselectivity studies using alpha- and beta
      substituted acids.

PMID- 11843575
TI  - Solution- and solid-phase synthesis of 4-hydroxy-4,5-dihydroisoxazole derivatives
      from enantiomerically pure N-tosyl-2,3-aziridine alcohols.
AB  - [reaction: see text] Enantiomerically pure N-tosyl-2,3-aziridine alcohols are
      directly converted into 4-hydroxy-4,5-dihydroisoxazole 2-oxides through oxidation
      to the corresponding aldehydes followed by in situ tandem nitroaldol
      intramolecular cyclization. This study was concerned with (i) the selection of a
      suitable aziridine activation, (ii) the preparation of the target 4-hydroxy-4,5
      dihydroisoxazole derivatives in solution, and (iii) the elaboration of a solid
      phase process using hydroxy Merrifield-supported nitroacetic acid ester.

PMID- 11843576
TI  - Short total synthesis of (+)-madindolines A and B.
AB  - [reaction: see text] A short and efficient total synthesis of (+)-madindolines A
      (1) and B (2), potent and selective inhibitors of interleukin 6, has been
      achieved. The synthesis features a key chelation-controlled 1,4
      diastereoselective acylation to generate the quaternary carbon and an
      intramolecular acylation of allylsilane to build up the cyclopentene unit.

PMID- 11843577
TI  - K(2)CO(3)-catalyzed Michael addition-lactonization reaction of 1,2-allenyl
      ketones with electron-withdrawing group substituted acetates. An efficient
      synthesis of alpha-pyrone derivatives.
AB  - [reaction: see text] Alpha-pyrone derivatives were synthesized via the base
      catalyzed or promoted reaction of 1,2-allenyl ketones and electron-withdrawing
      group substituted acetates. The reaction was believed to proceed through a
      Michael addition C-C double-bond migration-lactonization process.

PMID- 11843578
TI  - Inclusion behavior of thiacalix[4]arenetetrasulfonate toward water-miscible
      organic molecules studied by salting-out and X-ray crystallography.
AB  - [reaction: see text] Inclusion ability of thiacalix[4]arenetetrasulfonate (TCAS)
      toward water-miscible organic molecules such as alcohols, ketones, cyclic ethers,
      and so on was studied by salting-out of the inclusion complex. NMR spectra of the
      recovered precipitates showed size selectivity to include the guest molecules. X
      ray crystallographic analyses of TCAS salts including acetone and 1,4-dioxane
      suggested that guests are retained with the aid of cation coordination and H
      bonding.

PMID- 11843580
TI  - Theoretical analysis of the reaction pathway and the effect of the axial ligand
      for 3-oxobutylideneaminatocobalt(II)-catalyzed cyclopropanation.
AB  - [structure: see text] The reaction pathway of the cyclopropanation catalyzed by
      the 3-oxobutylideneaminatocobalt(II) complex was analyzed by the density
      functional method to reveal that the axial donor ligand produced two prominent
      effects. One is that the activation energy for the formation of the cobalt
      carbene complex was reduced and that the activation energy for the
      cyclopropanation step was increased. The other is that the distance of the
      carbene carbon above the ligand plane was shortened during the cyclopropanation
      step.

PMID- 11843579
TI  - Suzuki coupling approach for the synthesis of phenylene-pyrimidine alternating
      oligomers for blue light-emitting material.
AB  - [reaction: see text] Conjugated oligomers with an alternating phenylene
      pyrimidine structure have been synthesized by the successive Suzuki coupling
      reaction starting from 2-bromo-5-iodopyrimidine. The photoluminescence properties
      and quasi-reversible redox behavior of these oligomers make them applicable as an
      active material for a light-emitting device. Blue light-emitting
      electroluminescent devices with an external quantum efficiency up to 1.8% have
      been fabricated.

PMID- 11843581
TI  - Regiocontrolled synthesis of the trimeric quinone framework of conocurvone.
AB  - [reaction: see text] The trimeric quinone framework of conocurvone is crucial for
      its potent anti-HIV activity. A new synthesis of trimeric quinones based on
      stepwise substitution of the halogens in 2,3-dihaloquinones by hydroxyquinone
      anions is described. Chlorinated biquinones are key intermediates that undergo
      regiospecific substitution reactions to yield trimeric quinone monomethyl ethers.

PMID- 11843582
TI  - Total synthesis of (+)-crocacin D.
AB  - [structure: see text] The first asymmetric synthesis of (+)-crocacin D (4) is
      described. The key steps in the sequence are the stereoselective assembly of the
      stereotetrad via a substrate-controlled aldol reaction and anti-selective
      reduction, formation of the (E,E)-diene by a Stille cross-coupling between the
      stannane 8 and vinyl iodide 9, and the acylation of (Z)-enecarbamate 6 with the
      acid chloride derived from polyketide fragment 16 which introduced the (Z)
      enamide functionality.

PMID- 11843583
TI  - Synthesis of novel D-2'-deoxy-2'-C-difluoromethylene-4'-thiocytidine as a
      potential antitumor agent.
AB  - [reaction: see text] 2'-Deoxy-2'-C-difluoromethylene-4'-thiocytidine (4) as a
      potential antitumor agent was synthesized starting from L-xylose via 2-deoxy-2-C
      difluoromethylene-4-thiosugar as a key intermediate. An elimination product, 8,
      was always formed as the major product during removal of the protecting groups
      under acidic or basic conditions. However, utilizing neutral reaction conditions
      to remove the protecting groups afforded the desired product 4 exclusively.

PMID- 11843584
TI  - A beta-lactone route to chiral gamma-substituted alpha-amino acids: application
      to the concise synthesis of (S)-alpha-azidobutyro lactone and a natural amino
      acid.
AB  - [reaction: see text] Beta-lactones are useful synthetic intermediates allowing
      access to a number of functional arrays. In this report, enantiomerically pure 4
      trichloromethyl-2-oxetanone is shown to be a versatile amino acid synthon leading
      to a variety of gamma-substituted alpha-amino acid precursors. The utility of
      this methodology was demonstrated by the concise synthesis of a protected
      homoserine equivalent, alpha-azidobutyro lactone, and a naturally occurring alpha
      amino acid from the seeds of Blighia unijugata.

PMID- 11843586
TI  - Microwave-assisted synthesis of pinacol boronates from aryl chlorides catalyzed
      by a palladium/imidazolium salt system.
AB  - [reaction: see text] Aryl chlorides bearing electron-withdrawing groups react
      with bis(pinacol)borane 1 to give aryl boronates in good to excellent yields in
      the presence of a catalyst formed in situ from Pd(OAc)(2) and the imidazolium
      chloride 2. The reaction is greatly accelerated when carried out under microwave
      heating.

PMID- 11843585
TI  - Spiroiminodihydantoin is a major product in the photooxidation of 2'
      deoxyguanosine by the triplet states and oxyl radicals generated from
      hydroxyacetophenone photolysis and dioxetane thermolysis.
AB  - [reaction: see text] Photolysis of hydroxyacetophenone and thermolysis of the
      corresponding dioxetane afford spiroiminodihydantoin rather than 4,8-dihydro-4
      hydroxy-8-oxo-2'-deoxyguanosine (4-HO-8-oxodG) through the oxidation of 2'
      deoxyguanosine (dG) by triplet-excited hydroxyacetophenone and the peroxyl
      radicals derived thereof by alpha cleavage and subsequent oxygen trapping. The
      structure of the spiroiminodihydantoin is assigned by the SELINQUATE NMR
      technique, which unequivocally establishes the spirocyclic connectivity.

PMID- 11843587
TI  - Catalytic enantioselective fluorination of beta-keto esters by phase-transfer
      catalysis using chiral quaternary ammonium salts.
AB  - [reaction: see text] The catalytic enantioselective electrophilic fluorination
      promoted by quaternary ammonium salt from cinchonine as a phase-transfer catalyst
      is described. Treatment of beta-keto esters with N-fluorobenzenesulfonimide as
      the fluorine source under mild reaction conditions afforded the corresponding
      alpha-fluoro beta-keto esters in exellent yields with good to moderate
      enantiomeric excesses

PMID- 11843588
TI  - Synthesis of cyclic prodrugs of Aggrastat and its analogue with a modified
      phenylpropionic acid linker.
AB  - [structure: see text] The objective of this work was to synthesize cyclic
      prodrugs 1a and 1b from Aggrastat 2a and its analogue 2b, respectively, to
      improve their membrane permeation. Cyclic prodrugs 1a and 1b were formed using an
      ester bond between the -COOH group of Aggrastat or its analogue and the
      phenylpropionic acid linker 3 and an amide bond between the piperidinylamine and
      the -COOH group of the linker 3, respectively, as outlined in Scheme 4.

PMID- 11843589
TI  - An efficient route to alkyl chlorides from alcohols using the complex TCT/DMF.
AB  - [reaction: see text] Efficient conversion of alcohols and beta-amino alcohols to
      the corresponding chlorides (and bromides) can be carried out at room temperature
      in methylene chloride, using 2,4,6-trichloro[1,3,5]triazine and N,N-dimethyl
      formamide. This procedure can also be applied to optically active carbinols.

PMID- 11843590
TI  - Poised on the brink between a bistable complex and a compound.
AB  - [reaction: see text] An enmeshed supramolecular complex, based on a semi-dumbbell
      shaped component containing an asymmetrically substituted tetrathiafulvalene site
      and a 1,5-dioxynaphthalene site for encirclement by a cyclobis(paraquat-p
      phenylene) ring component and with a "speed bump" in the form of an thiomethyl
      group situated between the two recognition sites, has been self-assembled. This
      complex is a mixture in acetone solution of two slowly interconverting
      [2]pseudorotaxanes, one of which is on the verge of being a [2]rotaxane at room
      temperature.

PMID- 11843592
TI  - An efficient organometallic approach to new carbocyclic nucleoside analogues.
AB  - [reaction: see text] A general synthetic approach to monoprotected carbocyclic
      nucleoside analogues, having the nucleobase attached to a 3-hydroxymethyl-4
      trialkylsilyloxymethyl-cyclopent-2-en-1-yl scaffold, was developed. A (racemic)
      key intermediate was prepared by a cobalt-mediated Pauson-Khand reaction. In the
      course of the further synthesis, the introduction of the nucleobase was achieved
      with complete regio- and diastereoselectivity through a palladium-catalyzed
      allylic substitution.

PMID- 11843591
TI  - A novel phosphate chemosensor utilizing anion-induced fluorescence change.
AB  - [structure: see text] The neutral receptor N,N'-bis[3,5-di[(1
      pyrenylmethyl)carbamoyl]benzyl] pyridine-2,6-dicarbamide (2) provides a pseudo
      tetrahedron cleft and multiple hydrogen bondings to form a 1:1 complex with
      phosphate ion in a highly selective manner, by comparison with other anions (F(
      ), Cl(-), Br(-), SCN(-), AcO(-), NO(3)(-), ClO(4)(-), and HSO(4)(-)). The binding
      strength can be inferred from the emission intensity ratio of the pyrene monomer
      (lambda(max) 377 nm) to the excimer (lambda(max) 477 nm). Fluorescence titration,
      X-ray analysis, and NMR studies support a proposed complexation model.

PMID- 11843593
TI  - Preparation of sterically protected 3,4-bis[(2,4,6-tri-tert
      butylphenyl)phosphinidene]cyclobutene derivatives having ring-fused structures.
AB  - [reaction: see text] Sterically protected 3,4-diphosphinidenecyclobutenes, having
      ring-fused structures, were prepared. Structures of 8,9-bis[(2,4,6-tri-tert
      butylphenyl)phosphinidene]bicyclo[5.2.0]non-1(7)-ene and its
      dichloropalladium(II) complex were analyzed by X-ray crystallography. A
      geometrical change induced by the complex formation was exhibited by X-ray
      crystallographic analysis. The geometrical change in solution was also suggested
      by (1)H NMR spectroscopy in CDCl(3).

PMID- 11843594
TI  - Equilibrium constants and alkylation kinetics of two lithium enolates/LiHMDS
      mixed aggregates in THF.
AB  - [reaction: see text] Mixed aggregates between lithium enolates and lithium
      hexamethyldisilazide (LiHMDS) have been studied in THF using UV-vis spectroscopy.
      The equilibrium constants (K(agg)) between monomeric LiEn and monomeric LiHMDS
      are 760 and 560 M(-1) when LiEn are LiSIBP and LiBnPAT, respectively. The
      alkylation kinetics of the reactions with benzyl bromide were studied at 25
      degrees C. The rate constants for the mixed aggregates, k(Mixed), are
      substantially smaller than those of the monomeric enolates.

PMID- 11843595
TI  - Oxonia-cope rearrangement and side-chain exchange in the Prins cyclization.
AB  - [reaction: see text] Evidence is presented here for the mechanism of the Prins
      cyclization of benzylic homoallylic alcohols, which shows that the outcome of the
      reaction is dependent upon the substituents on the aromatic ring. The presence of
      an electron-rich aromatic ring favors an oxonia-Cope rearrangement yielding a
      symmetrical tetrahydropyran as the major product formed via a side-chain exchange
      process. In contrast, with electron-deficient aromatic rings the expected 2,4,6
      trisubstituted tetrahydropyran is formed.

PMID- 11843597
TI  - 1-tert-butoxy-2-tert-butoxycarbonyl-1,2-dihydroisoquinoline: a novel and
      chemoselective tert-butoxycarbonylation reagent.
AB  - [reaction: see text] The use of 1-tert-butoxy-2-tert-butoxycarbonyl-1,2
      dihydroisoquinoline (BBDI) as tert-butoxycarbonylation reagent for aromatic and
      aliphatic amine hydrochlorides and phenols in the absence of a base has been
      demonstrated. The reactions proceed chemoselectively in high yield under mild
      conditions.

PMID- 11843596
TI  - Copper-catalyzed coupling of alkylamines and aryl iodides: an efficient system
      even in an air atmosphere.
AB  - [reaction: see text] A mild method for the copper-catalyzed amination of aryl
      iodides is reported. This operationally simple C-N bond-forming protocol uses CuI
      as the catalyst and ethylene glycol as ligand in 2-propanol. A variety of
      functionalized aryl iodides as well as several amines were efficiently coupled
      using this method. This catalytic amination procedure is relatively insensitive
      to moisture and can be performed under an air atmosphere with comparable yield.
      Preliminary results on the amination of aryl bromides are also described.

PMID- 11843598
TI  - Synthesis of a conformationally locked version of puromycin amino nucleoside.
AB  - [reaction: see text] A conformationally locked carbocyclic version of puromycin
      amino nucleoside was synthesized via Mitsunobu coupling of a 3-azido-substituted
      carbocyclic moiety with 6-chloropurine without interference from the azido group
      reacting with triphenylphosphine. The requisite 3-azido-substituted carbocyclic
      pseudosugar was prepared by a double inversion of configuration at C3'
      (nucleoside numbering) involving a nucleophilic displacement with azide.

PMID- 11843599
TI  - Concise, regioselective synthesis of the ABC tristetrahydropyran of thyrsiferol
      and venustatriol.
AB  - [structure: see text] The ABC tristetrahydropyran substructure 1 of the natural
      products thyrsiferol (2) and venustatriol (3) has been synthesized in 14 steps
      from farnesyl acetate, with effective control of all aspects of regio- and
      stereoselectivity in the formation of each tetrahydropyran ring.

PMID- 11843600
TI  - A solid-phase route to N-cyanoamides.
AB  - [reaction: see text] A new method for the solid-phase synthesis of cyanamides is
      described. The attachment of a secondary amine to solid support is accomplished
      using Merrifield resin. After functionalization, cleavage is readily achieved
      with cyanogen bromide to afford the desired cyanamide.

PMID- 11843601
TI  - Lewis acid catalyzed sulfur transfer from a sultene to strained cyclic alkenes.
AB  - [reaction: see text] Sultene 1 reacts with cyclic alkenes under mild Lewis acid
      catalysis to form thiiranes diastereoselectively. With 1-methoxycyclooctene as
      sulfur acceptor, an unexpected insertion product is formed, which provides
      valuable mechanistic insight into the sulfur-transfer process.

PMID- 11843602
TI  - Synthesis of the liposidomycin diazepanone nucleoside.
AB  - [structure: see text] The synthesis of the liposidomycin degradation product 4
      from D-glucose establishes its stereochemistry as 5'S,6'S and, by incorporation
      of the earlier diazepanone relative stereochemical assignment, establishes the
      absolute stereochemistry of the liposidomycins 1 and 2 as 5'S,6'S,2'''S,3'''S.

PMID- 11843603
TI  - Thieno[3,4-b]-1,4-oxathiane: an unsymmetrical sulfur analogue of 3,4
      ethylenedioxythiophene (EDOT) as a building block for linear pi-conjugated
      systems.
AB  - [reaction: see text] An unsymmetrical analogue of 3,4-ethylenedioxythiophene
      (EDOT) has been synthesized by transetherification of 3,4-dimethoxythiophene.
      Electropolymerization leads to a stable electroactive polymer with
      electrochemical and electronic properties intermediate between those of the two
      symmetrical parent polymers poly(EDOT) and poly(3,4-ethylenedithiathiophene).
      Experimental work shows that the 2- and 5-positions possess a different
      reactivity, thus opening the possibility of synthesizing regioregular oligomers
      or polymers.

PMID- 11843604
TI  - Anion radical chain cycloaddition of tethered enones: intramolecular
      cyclobutanation and Diels-Alder cycloaddition.
AB  - [reaction: see text] The anion radicals of certain bis(enones), generated by
      cathodic reduction, are observed to participate in intramolecular
      cyclobutanation, yielding bicyclo[3.2.0]heptane derivatives through an anion
      radical chain mechanism. Evidence for stepwise cycloaddition involving distonic
      anion radical intermediates is presented. In addition to the novel anion radical
      cyclobutanations, an unprecedented intramolecular anion radical Diels-Alder
      product is observed. Parallel trends in substrate scope vis-a-vis the Co
      catalyzed bis(enone) cyclobutanation are discussed.

PMID- 11843605
TI  - A new entry to the isogeissoschizoid skeleton.
AB  - [reaction: see text] The tetracyclic isogeissoschizoid skeleton has been prepared
      by a novel route that involves the ozonolysis and double reductive amination of a
      cyclopentene, a nickel-catalyzed cyclization, and a late-stage Fischer indole
      synthesis.

PMID- 11843606
TI  - Diastereomer-differentiating hydrolysis of 1,3-diol-acetonides: a simplified
      procedure for the separation of syn- and anti-1,3-diols.
AB  - [reaction: see text] A new method to facilitate the separation of diastereomeric
      syn- and anti-1,3-diols is described. The method relies on the different
      hydrolysis rates of the corresponding diastereomeric acetonides. Treatment of a
      dichloromethane solution of syn- and anti-1,3-diol-acetonide with a catalytic
      amount of diluted aqueous hydrochloric acid leads to the selective cleavage of
      the anti diastereomer. The resulting anti-1,3-diol can be easily separated from
      the unchanged syn-1,3-diol-acetonide.

PMID- 11843607
TI  - Palladium-catalyzed stereocontrolled vinylation of azoles and phenothiazine.
AB  - [reaction: see text] Vinylation of various azoles (pyrrole, indole, carbazole,
      and their derivatives) and phenothiazine with vinyl bromides catalyzed by
      palladium-phosphine complexes results in the respective N-vinylazoles in 30-99%
      yields. This reaction with cis- and trans-beta-bromostyrenes is stereospecific
      giving the respective products with full retention of configuration.

PMID- 11843608
TI  - Generation of ketenes from acid chlorides using NaH/crown ether shuttle
      deprotonation for use in asymmetric catalysis.
AB  - [reaction: see text] We describe methodology for the in situ generation of
      reactive monosubstituted ketenes from acid chlorides through a shuttle
      deprotonation process using NaH as an inexpensive stoichiometric base and a crown
      ether cocatalyst. We have successfully applied this new procedure to the
      catalytic, asymmetric synthesis of beta-lactams and alpha-haloesters.

PMID- 11843609
TI  - First total synthesis of the 7,3'-linked naphthylisoquinoline alkaloid
      ancistrocladidine.
AB  - [structure: see text] The first total synthesis of the rare 7,3'-linked
      naphthylisoquinoline alkaloid, ancistrocladidine, has been completed. The key
      feature of the synthesis is the formation of the extremely hindered biaryl
      linkage by Pinhey-Barton ortho-arylation of a naphthol with an aryllead
      triacetate. The biaryl aldehyde formed is elaborated in 10 steps to form a 1:1
      mixture of ancistrocladidine and its atropisomer. Recrystallization of the
      mixture afforded ancistrocladidine, which was identical in all respects to the
      reported data.

PMID- 11843610
TI  - Total synthesis of (+)-dactylolide.
AB  - [reaction: see text] The total synthesis of the new cytotoxic marine macrolide
      (+)-dactylolide (1) has been achieved in nine steps from known vinyl bromide (-)
      AB. In addition, (+)-zampanolide (2) has been converted to (+)-dactylolide (1)
      via thermolysis.

PMID- 11843611
TI  - Unexpected dramatic substituent effect for tuning the selectivity in the double
      ring-closing metathesis reaction of N-containing tetraenes. An efficient
      synthesis of bicyclic izidine alkaloid skeletons.
AB  - [reaction: see text] A double ring-closing metathesis reaction for the efficient
      construction of the fused bicyclic izidine alkaloid skeleton was developed. In
      this reaction, high selectivity was realized by tuning of electronic and steric
      effects of substituents in the N-containing tetraenes. It was observed that the
      reactivity of electron-rich carbon-carbon double bonds is higher than that of
      electron-deficient ones. A brief mechanistic study is also discussed.

PMID- 11843612
TI  - Synthesis of the core structure of apicularen a by transannular cyclization.
AB  - [reaction: see text] An approach to the macrocyclic core of apicularen A is
      described. Thus, cross-coupling of the aryl triflate 7 with the vinylstannane 19
      provided the styrene 20. Deprotection led to the dihydroxy acid 22. Through a
      size-selective macrolactonization, the 12-membered macrolactone 23 was obtained.
      Treatment of 24 with N-phenyl selenophthalimide gave the desired trans-pyran 24.
      This approach might parallel the biosynthetic pathway.

PMID- 11843613
TI  - Total synthesis of the mycolactones.
AB  - [structure: see text] The first total synthesis of the mycolactones is reported.
      This work unambiguously confirms our earlier relative and absolute stereochemical
      assignment of the mycolactones.

PMID- 11843614
TI  - General route from simple methyl, alkyl, and cycloalkyl arenes to polycyclic
      cyclopentenyl aryl derivatives. The CpFe(+) group as an activator and tag.
AB  - [reaction: see text] The CpFe(+) group activates the perallylation of the
      benzylic groups of arenes using KOH and allylbromide under ambient conditions.
      This reaction can be followed by ruthenium-catalyzed RCM metathesis using Grubbs'
      catalyst at room temperature to give polycyclic aromatic derivatives in high
      yields, and these products are easily separated from the catalyst by extraction
      using ether. Alternatively, the RCM metathesis can be best carried out in ionic
      liquids at 80 degrees C, and extraction using ether is then facile.

PMID- 11843615
TI  - 2H-Azirine 3-phosphonates: a new class of chiral iminodienophiles. Asymmetric
      synthesis of quaternary piperidine phosphonates.
AB  - [reaction: see text] Diels-Alder reactions of enantiomerically enriched 2H
      azirine 3-phosphonates and dienes stereoselectively furnish optically pure,
      bicyclic aziridine adducts that on hydrogenation afford the first examples of
      enantiopure quaternary piperidine phosphonates.

PMID- 11843616
TI  - Alkynenitriles: chelation-controlled conjugate additions.
AB  - [reaction: see text] Chelation between gamma-hydroxybutynenitrile and Grignard
      reagents triggers a particularly facile anionic conjugate addition reaction.
      Structurally diverse Grignard reagents add with equal efficiency, providing an
      intermediate anion that stereoselectively alkylates benzaldehyde in an overall
      addition-alkylation reaction.

PMID- 11843617
TI  - Unprecedented microwave effects on the cycloaddition of fulvenes. A new approach
      to the construction of polycyclic ring systems.
AB  - [reaction: see text] Novel cycloaddition reactions between fulvenes and various
      alkenes and alkynes are promoted by the use of microwave irradiation. These
      processes result in the formation of intriguing polycyclic ring systems such as
      those found in isobarbatene, alcyopterosin, and enokipodin A. Importantly, these
      reactions do not occur under conventional thermolytic conditions.

PMID- 11843618
TI  - Conjugate addition of organosiloxanes to alpha,beta-unsaturated carbonyl
      compounds catalyzed by a cationic rhodium complex.
AB  - [reaction: see text] A novel, additive-free, and clean conjugate addition
      reaction of organosiloxanes to alpha,beta-unsaturated carbonyl compounds
      catalyzed by a cationic rhodium complex in water-containing solvent has been
      developed. A plausible reaction mechanism involving the additive-free
      transmetalation step between the rhodium complex and the silicon reagent is
      proposed.

PMID- 11843619
TI  - Unifying themes in DNA replication: reconciling single molecule kinetic studies
      with structural data on DNA polymerases.
AB  - Structural data suggest that DNA polymerases, from at least three different
      families, employ common strategies for carrying out DNA replication. Universal
      features include a large conformational change in the enzyme-template complex and
      a conserved active-site geometry that imposes a sharp kink at the 5  end of the
      template strand. Recent single molecule experiments have shown that stretching
      the DNA template markedly alters the rate of DNA synthesis catalyzed by these
      motor enzymes. From these data, it was previously inferred that T7 DNA polymerase
      and two related enzymes convert two or four (depending on the enzyme) single
      stranded (ss) template bases to double helix geometry in the polymerase active
      site during each catalytic cycle. We discuss structural data on related DNA
      polymerases, which suggest that only one (ss) template base is contracted to
      dsDNA geometry during the rate-limiting step of each replication cycle. Previous
      interpretations relied upon the global stretching curves for DNA polymers alone
      (with no reference to the enzyme or the structure of the transition state). In
      contrast, we present a structurally guided model that presumes the force
      dependence of the replication rate is governed chiefly by local interactions in
      the immediate vicinity of the enzyme s active site. Our analysis reconciles
      single molecule kinetic studies with structural data on DNA polymerases.

PMID- 11843620
TI  - Correlation of secondary structures of bradykinin B1 receptor antagonists with
      their activity.
AB  - The secondary structure of a bradykinin B(1)receptor antagonist B-10324 (F5C-Lys
      (1)- Lys(0)-Arg(1)-Pro(2)- Hyp(3)-Gly(4)-CpG(5)- Ser(6)-DTic(7)-CpG(8)) was
      determined by NMR at 800MHz. The conformational data are compared with those
      obtained previously for two bradykinin B(1) receptor antagonists, namely B-9858
      (Lys-(1)- Lys(0)-Arg(1)-Pro(2)- Hyp(3)-Gly(4)-Igl(5)- Ser(6)-DIgl(7)-Oic(8)) and
      B-10148 (Lys-(1)-Lys(0)-Arg(1)- Pro(2)-Hyp(3)-Gly(4)- Igl(5)-Ser(6)-DF5F(7)-
      Oic(8)). The abnormal amino acids are: Hyp, trans-4- hydroxyproline; Tic, 1, 2,
      3, 4-tetrahydroisoquinoline-3-carboxylic acid; Oic, (2S, 3aS, 7aS)
      octahydroindole-2-carboxylic acid; Igl, alpha(2- indanyl)glycine; F5F, 2,3,4,5,6
      pentafluorophenylalanine; CpG, alpha- cyclopentylglycine. F5C,
      pentafluorocinnamoyl, is the N-terminal protecting group and is not involved in
      the peptide secondary structure. B-10324 contains an N-terminal Pro(2)- CpG(5)
      distorted type II beta-turn whereas the rest of the peptide is random. A salt
      bridge is not observed between the carboxylate group at the C-terminal end and
      the Arg(1) side chain, in contrast to that previously observed for B-9858 and B-
      10148. The conformations are correlated with the measured B(1) receptor
      antagonist activities (J.-F. Larrivee, L. Gera, S. Houle, J. Bouthillier, D. R.
      Bachvarov, J. M. Stewart and F. Marc au, Br. J. Pharmacol. 131, 885-892 (2000)).
      The importance of the N-terminal beta-turn is highlighted.

PMID- 11843621
TI  - Modeling the "glass" transition in proteins.
AB  - A model of a protein as a disordered system of identical spherical particles
      (which imitate protein side chains) interacting with each other via a repulsive
      soft sphere potential U(r) infinity r(-beta) is constructed. The particles
      undergo the conformational motion (CM) within their own harmonic conformational
      potentials around some mean equilibrium positions ascribed by the tertiary
      structure of the protein. A first principles calculation of the positional
      correlation functions for the CM is carried out. The general analysis is
      exemplified by the case in which the mean equilibrium positions of the particles
      form a cubic tightly-packed (face- centered) lattice (each particle has 12
      nearest neighbors) with the step b(hydr) =6.6 A (the average distance between the
      centers of mass of hydrated protein subunits). The model yields dramatic slowing
      down of the relaxation with the decrease of temperature followed by a sharp glass
      transition at some crossover temperature T(c) < 200 K. At the transition the
      liquid-like dynamic behavior (the correlation functions tend to zero with time)
      is altered by the glass-like one (the correlation functions tend with time to
      some non-zero limit). In the liquid-like region above the crossover temperature
      the relaxation exhibits distinct alpha-process following the beta-one. The glass
      transition results from the interaction of the particles. Thus the model suggests
      that namely direct interactions of the fragments of protein structure rather than
      protein-solvent interactions are the origin of the phenomenon of the glass
      transition. The known increase of T(c) up to 300 K at dehydration of the protein
      is attributed to the known concomitant compression of the globule upon drying by
      about 4-6% so that positions of individual atoms displace by about 0.6 A (modeled
      by the decrease of the step of the lattice b by 0.6 A so that b(dehydr)=6 A). The
      model suggests that the solvent influences the phenomenon of the glass transition
      indirectly determining the tertiary structure of the protein rather than via own
      freezing. In the model the transition from the liquid-like dynamic behavior to
      the glass-like one can be obtained even in a cluster containing a few particles.
      Thus the results of the model can be considered as an argument in favor of the
      point of view that the transition to the glassy behavior can take place for a
      very small domains of the protein comprising only several constituting fragments
      of its structure. The model predicts that for the dehydrated protein the alpha
      relaxation process is strongly repressed.

PMID- 11843622
TI  - A gene coding for a novel protein specific to the olfactory rosettes of Atlantic
      salmon.
AB  - We have isolated a 1.6 kb clone from a cDNA library made from the olfactory
      rosettes of the Atlantic salmon (Salmo salar). The clone contains a 1200 bp, open
      reading frame (named OSC) which codes for a protein with 400 amino-acid residues
      (Oscp). The mRNA corresponding to OSC is strongly expressed in the olfactory
      rosettes and weakly expressed in gills but is expressed in only these two
      tissues. This suggests that Oscp may have a specific and important role in
      olfaction. The sequence of Oscp suggests that it is not globular. Predictions
      show only a small fraction of alpha-helix. Oscp is hydrophilic but with the
      number of positively charged residues equal to the number of negatively charged
      residues. No closely similar protein can be found on the basis of homology
      searches or hydrophobicity comparisons. However, a 44 residue segment (G300
      through K343) is significantly homologous to a segment of alpha-lactalbumin (G51
      through K94). The similarities include the 19 residues of the "alpha- lactalbumin
      lysozyme C signature," the ten residues of the Ca(2+) binding elbow and the four
      cysteine residues which provide two key disulfide links in alpha-lactalbumin and
      lysozyme C. Two more Cys residues are also very similarly placed. We conclude
      that the gene OSC codes for a unique protein which most likely contains a
      specific site for binding Ca(2+) and plays a unique role in the signal pathway of
      olfaction in salmon.

PMID- 11843623
TI  - Pressure-induced transformation of alpha-helix to beta-sheet in the secondary
      structures of amyloid beta (1-40) peptide exacerbated by temperature.
AB  - The effect of pressure on the conformational structure of amyloid beta (1-40)
      peptide (A beta(1-40)), exacerbated with or without temperature, was determined
      by Fourier transform infrared (FT-IR) microspectroscopy. The result indicates the
      shift of the maximum peak of amide I band of intact solid A beta(1-40) from 1655
      cm(-1) (alpha-helix) to 1647-1643 cm(-1) (random coil) with the increase of the
      mechanical pressure. A new peak at 1634 cm(-1) assigned to beta-antiparallel
      sheet structure was also evident. Furthermore, the peak at 1540 cm(- 1) also
      shifted to 1527 (1529) cm(-1) in amide II band. The former was assigned to the
      combination of alpha-helix and random coil structures, and the latter was due to
      beta-sheet structure. Changes in the composition of each component in the
      deconvoluted and curve-fitted amide I band of the compressed A beta(1-40) samples
      were obtained from 33% to 22% for alpha-helix/random coil structures and from 47%
      to 57% for beta-sheet structure with the increase of pressure, respectively. This
      demonstrates that pressure might induce the conformational transition from alpha
      helix to random coil and to beta- sheet structure. The structural transformation
      of the compressed A beta(1-40) samples was synergistically influenced by the
      combined effects of pressure and temperature. The thermal-induced formation of
      beta-sheet structure was significantly dependent on the pressures applied. The
      smaller the pressure applied the faster the beta-sheet structure transformed. The
      thermal-dependent transition temperatures of solid A beta(1-40) prepared by
      different pressures were near 55-60 degrees C.

PMID- 11843624
TI  - Structure elucidation of the hepatitis B virus encapsidation signal by NMR on
      selectively labeled RNAs.
AB  - Hepatitis B virus (HBV) HBV is DNA virus with a unique replication strategy,
      which involves reverse transcription of its pregenomic RNA. Essential for this
      reverse transcription are the 5'- and 3'-ends of its pregenomic RNA (5'-RT-RNA
      and 3'-RT-RNA, respectively) which form conserved bulged stem-loop structures.
      The 5'-RT-RNA consists of a 67 nucleotide bulged stem-loop structure, epsilon,
      which constitutes the signal for encapsidation of the pregenomic RNA and
      subsequent reverse transcription. The reverse transcriptase (RT) initially binds
      to the completely conserved apical loop of epsilon and a 4-nucleotide primer is
      synthesized from the adjacent 6-nucleotide bulge. Structural studies of epsilon
      can provide important parameters required for the design of RNA targeted anti-
      viral drugs directed against Hepatitis B virus. NMR studies of large RNA systems
      (> ca. 50 nucleotides) require novel approaches, e.g., different labeling schemes
      and reduction of the system into separate structural building blocks. Recently, a
      new method of synthesizing (13)C/(15)N/(2)H labeled nucleotides has been
      developed based on converting specifically labeled glucose and bases into
      nucleotides by using enzymes from the pentose phosphate pathway and nucleotide
      and salvage pathways. These NTPs give a large freedom in designing different
      labeling patterns in in vitro synthesized RNAs under study for NMR. This opens up
      the way for NMR studies of RNAs that are considerably above the present size
      limit (up to 150 nucleotides). Here this new technique is applied for structural
      studies on 27, 36 and 61 nucleotides long RNA fragments, mimicking different
      regions of epsilon.

PMID- 11843625
TI  - Conformational preferences of anticodon 3'-adjacent hypermodified nucleic acid
      base cis-or trans-zeatin and its 2-methylthio derivative, cis-or trans-
      ms(2)zeatin.
AB  - Conformational preferences of the hypermodified nucleic acid bases N6-(Delta(2)
      cis-hydroxyisopentenyl)adenine, cis-io(6)Ade also known as cis-zeatin, and N(6)
      (Delta(2)-trans-hydroxyisopentenyl)adenine, trans-io(6)ade or trans-zeatin, and 2
      methylthio derivatives of these cis-ms(2)io(6)Ade or cis-ms(2)zeatin, and trans
      ms(2)io6Ade or trans-ms(2)zeatin have been investigated theoretically by the
      quantum chemical Perturbative Configuration Interaction with Localized Orbitals
      (PCILO) method. Automated geometry optimization using quantum chemical MNDO, AM1
      and PM3 methods has also been made to compare the salient features. The predicted
      most stable conformation of cis-io(6)Ade, trans-io(6)Ade, cis-ms(2)io(6)Ade and
      trans-ms(2)io(6)Ade are such that in each of these molecules the isopentenyl
      substituent spreads away (has "dista" conformation) from the five membered ring
      imidazole moiety of the adenine. The atoms N(6), C(10) and C(11) remain coplanar
      with the adenine ring in the predicted preferred conformation for each of these
      molecules. In cis-io(6)Ade as well as cis-ms(2)io(6)Ade the hydroxyl oxygen may
      participate in intramolecular hydrogen bonding with the H-C(10)-H group. In trans
      io(6)Ade the hydroxyl group is oriented towards the H-C(2) instead. This
      orientation is retained in trans-ms(2)io(6)Ade, possible O-H...S hydrogen bonding
      may be a stabilizing factor. In all these four modified adenines C(11)-H is
      favourably placed to participate in intramolecular hydrogen bonding with N(1). In
      cis-ms(2)io(6)Ade as well as trans-ms(2)io(6)Ade the 2-methylthio group
      preferentially orients on the same side as C(2)-N(3) bond, due to this non
      obstrusive placing, orientation of the hydroxyisopentenyl substituent remains
      unaffected by 2-methylthiolation. Thus the N(1) site remains shielded
      irrespective of the 2-methylthiolation status in these various cis-and trans
      zeatin analogs alike. Firmly held orientation of hydroxyisopentenyl substituent
      in zeatin isomers and derivatives, in contrast to adaptable orientation of
      isopentenyl substituent in i(6)Ade and ms(2)i(6)Ade, may account for the
      increased efficiency of suppressor tRNA and reduced codon context sensitivity
      accompanied with the occurrence of ms(2)-zeatin (ms(2)io(6)Ade) modification.

PMID- 11843626
TI  - A new peculiar DNA structure: NMR solution structure of a DNA kissing complex.
AB  - The deoxyoligoribonucleotide d(CTTGCTGAAGCGCGCACGGCAAG) (dSL1) corresponding to
      the reverse transcripted sequence of the dimerization initiation site SL1 of HIV-
      1(Lai) RNA was synthesized using phosphoramidite chemistry. Like its
      oligoribonucleotide counterpart, dSL1 dimerized spontaneously in solution. Here
      we report the first NMR solution structure of a kissing complex formed with two
      DNA strands. The melting point of the DNA dimer (35 degrees C) was found slightly
      higher than the one of the corresponding RNA dimer (32 degrees C). Despite this
      only slight difference in melting point, several structural differences were
      observed between the ribo- and the deoxyribo- dimers. The solution structure of
      the deoxy- dimer was a symmetric homodimer with a loop-loop interaction
      stabilized by four central G-C base-pairs, a head to tail A-A base-pair
      arrangement between the A8 residues of the two strands and a stacking of A9 with
      C15. As a consequence, G10 was not paired and occupied a position outside the
      stem and the loop. Each stem was formed by seven base-pairs whose axis made an
      angle of about 100 degree with the plane of the loops. The distortion of the
      helix at the junction of the stem and of the loop induced a fold up of the A8pA9
      step with a phosphate-phosphate distance lowered to 4.5 A. The plane of the non
      canonical A-A base-pair was oriented perpendicularly to the axis of the stems.
      The four central base-pairs formed an open fan-shaped motif with an angle of 20
      degrees between the bases and each of them was oriented perpendicularly to the A8
      A8 plane. The deviation of the computed chemical shifts and the experimental ones
      for the aromatic proton was always less than 0.25ppm for each of the 16 converged
      solution structures and their average less than 0.1ppm.

PMID- 11843627
TI  - Effect of flanking residues on CA and AA dinucleotides: some rationale.
AB  - Effect of flanking base pairs on CA and AA dinluceotide step-geometry has been
      studied using molecular dynamics method. Sixteen dodecameric sequences are
      constructed for each doublet with all possible bases at their 5' and 3' positions
      along with their complementary sequences. Structural parameter, formation of
      Extra Watson Crick bifurcated hydrogen bonds along or across the strands and
      effect of sodium ions are studied for these sequences. It is found that geometry
      of CA doublet step is perturbed by the neighboring base pairs, which might be due
      to inherent flexibility of the step. Flexible character of CA step is reflected
      in its low bifurcated hydrogen bond formation capability and lower preference of
      sodium ions to enter in minor or major grooves. AA step on the other hand is
      quite rigid according to different structural parameters and respond much less to
      environmental changes due to formation of strong Extra Watson-Crick hydrogen
      bonds.

PMID- 11843628
TI  - Occurrence of DNA sequences specifically recognized by drugs in human promoters.
AB  - Several DNA-binding drugs are being developed to create tailored molecules which
      can discriminate among the different sequences of the whole genome. By
      discriminating among specific sites in DNA, these molecules may provide optimal
      drug therapy. The complete sequencing of the human genome offers a wealth of DNA
      targets to be analyzed as potential drug-binding sites. To increase our
      understanding of DNA-drug interactions and their selectivity, we have studied the
      relative and absolute occurrence of CG-rich sequences, of various lengths, in
      human gene promoters. In several promoters, including those of oncogenes, cell
      cycle regulation factors, tumor suppressors and housekeeping genes, the presence
      of potential binding sites containing CpG steps (in which many drugs are known to
      intercalate) is variable, but in many cases these sites are not randomly
      distributed. Sequences 6-7 base pairs in length, like CGCCCG or CGCCCCG, occur
      only once in some promoters, thus they may be potentially specific therapeutic
      targets.

PMID- 11843629
TI  - Experimental studies on the nature of bonding of DNA*bipyridyl
      (ethylenediamine)platinum(II) and DNA*netropsin complexes in solution and
      oriented wet-spun films.
AB  - The stability of complexes of NaDNA with bipyridyl- (ethylenediamine)platinum(II)
      (abbreviated [(bipy)Pt(en)](2+)) and with netropsin has been studied using two
      techniques: (i) ultraviolet (UV) melting experiments were done on NaDNA*
      [(bipy)Pt(en)](2+), showing that the [(bipy)Pt(en)](2+) ligand stabilizes the DNA
      double helix structure; and (ii) swelling measurements (via optical microscopy)
      as a function of relative humidity were done on wet-spun oriented films of
      NaDNA*[(bipy)Pt(en)](2+) and of NaDNA*netropsin. The swelling data shows that an
      irreversible transition of the films occurs at high relative humidity, first for
      the NaDNA*netropsin, then for pure NaDNA, and lastly for the
      NaDNA*[(bipy)Pt(en)](2+). These results are indicative that the
      [(bipy)Pt(en)](2+) complex stabilizes the intermolecular bonds which mediate the
      film swelling characteristics. A model is suggested for the binding of
      [(bipy)Pt(en)](2+) to DNA to explain why the swelling experiments show this
      ligand as increasing the intermolecular bond strength between the DNA double
      helices, while netropsin decreases this degree of stabilization.

PMID- 11843630
TI  - Formation and thermodynamic stability of intermolecular (R*R*Y) DNA triplex in
      GAA/TTC repeats associated with Freidreich's ataxia.
AB  - It is well established that GAA/TTC base triplet expansion is the cause of
      degenerative disorder in Freidreich's Ataxia. It is also known that these repeat
      sequences fold back to form the unusual intramolecular triple helix structures in
      DNA of the type Pyrimidine *Purine *Pyrimidine or Purine *Purine*Pyrimidine. In
      this paper we report on the stability of Purine *Purine*Pyrimidine intermolecular
      triple helix DNA containing GAA/TTC repeats under physiological conditions. Using
      the oligonucleotides 5' TCGC GAA GAA GAA GAA GAA CGCT 3', 5'-AGCG TTC TTC TTC TTC
      TTC GCGA-3' for duplex and 5'-AAG AAG AAG AAG AAG -3' as triplex forming strand
      (TFO), we have established the formation of triplex by UV-melting temperature
      (Tm), stoichiometry of mixing and circular dichroic spectra. This was further
      confirmed by gel-retardation assay. The thermodynamic parameters Delta G, Delta H
      and Delta S for both duplex and triplex formation were determined at different
      salt concentrations. The results suggest the formation of a stable
      intermolecular, anti - parallel triplex in GAA/TTC repeat sequences where each
      repeat unit contains two A*A*T and one G*G*C triplet. The therapeutic agents and
      TFOs, which competitively inhibit the in-vivo intra-molecular triplex by
      formation of a more stable inter-molecular triplex, could be used to reverse the
      transcription deficit in GAA/TTC expansions in Frataxin gene.

PMID- 11843631
TI  - Structural analysis of the rDNA intergenic spacer of Tuber borchii.
AB  - The sequence and characterisation of the entire nuclear rDNA intergenic spacer
      (IGS) for the genus Tuber are presented. Sequence analyses showed that the
      organisation of the Tuber borchii rDNA IGS is typical of rDNA spacers, consisting
      of a central repetitive region and flanking unique sequences on either side.
      Direct repeats, symmetry elements, tandem repeats and possible areas of
      recombination were found. The putative ends of the 25S and 17S rDNA were
      identified. The presence of 5S rDNA in the IGS region was excluded.

PMID- 11843632
TI  - Differential scanning calorimetric study of the binding of the primary water of
      hydration to nucleosides.
AB  - Differential scanning calorimetry was used to study the water of hydration of all
      of the nucleosides at 59% relative humidity. Hydration was observed in pristine
      samples of guanosine, (rG), deoxyguanosine, (dG), and deoxyadenosine, (dA). Two
      inequivalent water sites were observed in dG and one site in rG. Re-hydration was
      observed in rG and dG, but not in dA. The activation energies for rG were 0.697
      +/- 0.051 eV and 0.683 plus minus 0.090 eV for pristine and cycled samples
      respectively. dG had activation energies of 0.726 +/- 0.026 eV and 0.997 +/-
      0.034 eV for the first and second peaks in the pristine samples while the
      activation energy for cycled dG was 0.671 +/- 0.133 eV.

PMID- 11843633
TI  - 23Na NMR study of the interaction between hyaluronan and the bications Ca(++),
      Mg(++) and Cu(++).
AB  - The relaxation rate R = pi Delta nu(1/2) of the quadrupolar (23)Na nucleus was
      measured at pH approximately 7 using a 200 MHz NMR spectrometer with a view to
      observe the interaction between hyaluronan and its natural counterion Na(+) and
      the bications Ca(++), Mg(++) and Cu(++). An interpretation of our results, by
      means of the "entropy of fluctuations" concept of Na(+), is presented. We show
      that Cu(++) ions are more effective than Ca(++) and Mg(++). A possible model of
      complexation of Cu(++) in a cage formed by the 1-4 glycosidic bond, the
      carboxylate side-chain and the acetoamide side-chain is proposed, according to
      electrostatic potential computations using the ZINDO1 quantum semi empirical
      method.

PMID- 11843634
TI  - Water as a structural element in a channel: gating in the Kcsa channel, and
      implications for voltage-gated ion channels.
AB  - Water is becoming understood as a structural element in proteins. Here we are
      concerned with one particular type of protein, ion channels. The S. Lividans KcsA
      K(+) channel, the X-ray structure of which is known, is gated by protons (i.e, by
      a drop in pH). Ab initio calculations suggest that an H(5)O(2) group, partially
      charged, connects the E118 residues in the gating region, when the four residues
      have a -2 net charge, but that the hydrogen bonding is not strong enough to do
      this when the charge becomes -1. The H(5)O(2) group would block the channel, in
      the -2 state, and prevent motion of the four transmembrane (TM) segments of the
      protein, by binding them. With the weaker bond in the -1 state, the TM segments
      would be able to separate (as they have been found to do experimentally, opening
      the channel. Voltage gated channels have four additional TM segments for each of
      the four domains of the channel protein. These appear to allow motion of protons;
      in fact there is evidence that the initial step in gating must be the transfer of
      a proton. We have earlier shown that the transfer of a single proton between two
      methylamines under the influence of a field is possible, as proton tunneling.
      Subsequent steps are hypothesized to result from four proton transfer cascades of
      about three protons each, triggered by the initial proton transfer. We suggest
      that the extra 4 TM segments of the voltage gated channel act as a voltage to
      proton-current transducer. Water, held by hydrogen bonds, is also suggested as
      the source of the accessibility data found with MTS reagents, based largely on
      simulations, our earlier Monte Carlo simulations as well as molecular dynamics
      studies reported by others. These waters may also play a structural role in the
      protein.

PMID- 11843635
TI  - Tazarotene is an effective therapy for elastosis perforans serpiginosa.

PMID- 11843636
TI  - The beautiful place.

PMID- 11843637
TI  - Follicular mucinosis: a critical reappraisal of clinicopathologic features and
      association with mycosis fungoides and Sezary syndrome.
AB  - CONTEXT: Beginning in 1957, patients have been described with localized alopecia
      characterized histopathologically by mucin deposition within hair follicles
      (follicular mucinosis [FM]). At least 2 distinct diagnostic entities have been
      proposed: one occurring in children and young adults without association with
      other diseases ("idiopathic" FM), the other occurring in elderly patients and
      associated with mycosis fungoides or Sezary syndrome ("lymphoma-associated" FM).
      OBJECTIVE: To determine whether idiopathic and lymphoma-associated FM are
      distinct or related entities. DESIGN: Case series. SETTING: Department of
      Dermatology, University of Graz, Graz, Austria. PATIENTS: Forty-four patients
      with FM were divided into 2 groups. Group 1 comprised 16 patients (mean age, 37.5
      years) with no associated mycosis fungoides or Sezary syndrome; group 2 was made
      up of the other 28 (mean age, 52.2 years), who had clinicopathologic evidence of
      cutaneous T-cell lymphoma. RESULTS: Mean age was lower in patients with
      idiopathic FM, but a considerable overlapping among the 2 groups was present.
      Location on the head and neck region was common in both groups, but most patients
      with lymphoma-associated FM had lesions also on other body sites. In fact,
      solitary lesions at presentation were common in patients with idiopathic FM (11
      [68.8%] of 16 patients), but uncommon in those with lymphoma-associated FM (2
      [7.1%] of 28 patients). Histopathologic findings did not allow clear-cut
      differentiation of the 2 groups. Finally, a monoclonal rearrangement of the T
      cell receptor gamma gene was demonstrated by polymerase chain reaction analysis
      in about 50% of tested cases from each group. CONCLUSIONS: Criteria previously
      reported to differentiate idiopathic from lymphoma-associated FM proved
      ineffective. In analogy to localized pagetoid reticulosis (Woringer-Kolopp
      disease), small-plaque parapsoriasis, and so-called solitary mycosis fungoides,
      idiopathic FM may represent a form of localized cutaneous T-cell lymphoma.

PMID- 11843638
TI  - Follicular mycosis fungoides, a distinct disease entity with or without
      associated follicular mucinosis: a clinicopathologic and follow-up study of 51
      patients.
AB  - OBJECTIVE: To determine the clinicopathologic features and the disease course of
      patients with follicular mycosis fungoides (MF). DESIGN: A multicenter, 14-year,
      retrospective cohort analysis. SETTING: Dutch Cutaneous Lymphoma Group. PATIENTS:
      Fifty-one patients with the clinicopathologic features of follicular MF with (n =
      49) or without (n = 2) associated follicular mucinosis. Follow-up data were
      compared with those of 158 patients with the classic epidermotropic type of MF,
      including 122 patients with generalized plaque-stage MF (T2 N0 M0) and 36
      patients with tumor-stage MF (T3 N0 M0). OBSERVATIONS: Characteristic clinical
      features not or rarely observed in classic MF were the preferential localization
      of the skin lesions in the head and neck region (45 of 51 patients), the presence
      of follicular papules, alopecia, acneiform lesions, mucinorrhoea, and often
      severe pruritus. Characteristic histologic findings were the presence of
      perifollicular neoplastic infiltrates with a variable degree of folliculotropism,
      but generally no epidermotropism, follicular mucinosis (49 of 51 cases), and
      often a considerable admixture of eosinophils and plasma cells. Response on
      initial treatment, risk of disease progression (development of extracutaneous
      disease and/or death from lymphoma), and disease-specific and overall survival of
      patients with follicular MF were worse than in classic MF patients. The actuarial
      disease-specific survival was 68% at 5 years and 26% at 10 years. CONCLUSIONS:
      Follicular MF shows distinctive clinicopathologic features, is more refractory to
      treatment, and has a worse prognosis than the classic type of MF; it should be
      considered a distinct type of cutaneous T-cell lymphoma. Based on these results
      and those of other studies, we suggest the term follicular MF for cases with or
      without associated follicular mucinosis.

PMID- 11843640
TI  - Junctional CD8+ cutaneous lymphomas with nonaggressive clinical behavior: a CD8+
      variant of mycosis fungoides?
AB  - OBJECTIVE: To evaluate the clinical and prognostic features in primary cutaneous
      CD8+ T-cell lymphomas, which are rare and considered to be aggressive cutaneous
      lymphoproliferative disorders. DESIGN: Single-center retrospective study.
      SETTING: Lymphoma clinic (referral center) of a university hospital. PATIENTS:
      Three patients presented with CD8+ cutaneous lymphoma characterized by a
      patchlike pattern and hyperpigmentation. RESULTS: Histological analysis revealed
      a CD3+, CD8+ small-cell infiltrate showing a remarkable affinity to the
      dermoepidermal junction zone. Clonality for the T-cell receptor gamma chain was
      detected by polymerase chain reaction followed by denaturing gradient gel
      electrophoresis. The clinical presentation lasted several years (6 and 9 years,
      respectively) before the correct diagnosis was made. Treatment with nontoxic
      approaches (UV-B and local steroids) was successful. Aggressive clinical behavior
      was not observed. CONCLUSIONS: Our 3 cases of junctional CD8+ cutaneous T-cell
      lymphomas were characterized by hyperpigmentation and nonaggressive clinical
      behavior. This type of lymphoma, which can be considered a CD8+ mycosis fungoides
      variant, must be distinguished from other types of cutaneous CD8+ lymphomas so
      that overtreatment can be avoided.

PMID- 11843641
TI  - Exploration of "alternative" and "natural" drugs in dermatology.
AB  - OBJECTIVE: To review some of the promising natural remedies within dermatology to
      explore their potential clinical benefit in supplementing conventional drugs.
      DATA SOURCES: MEDLINE searches from January 1966 through October 2000 and Science
      Citation Index searches from January 1974 through October 2000 were conducted.
      STUDY SELECTION: Primary importance was given to in vivo and in vitro controlled
      studies, the results of which encourage further exploration. DATA EXTRACTION: The
      controls used, the statistical approach to analysis, and the validity of the
      experimental method analyzed were considered particularly important. Data were
      independently extracted by multiple observers. DATA SYNTHESIS: Natural remedies
      seem promising in treating a wide variety of dermatologic disorders, including
      inflammation, phototoxicity, psoriasis, atopic dermatitis, alopecia areata, and
      poison oak. CONCLUSIONS: The alternative medications presented seem promising,
      although their true effects are unknown. Many of the presented studies do not
      allow deduction of clinical effects. Further experimentation must be performed to
      assess clinical benefit.

PMID- 11843642
TI  - Skin colonization by Malassezia species in neonates: a prospective study and
      relationship with neonatal cephalic pustulosis.
AB  - OBJECTIVES: To assess skin colonization by Malassezia species in full-term
      healthy newborns, to investigate factors associated with colonization, and to
      look at acnelike cephalic pustulosis associated with this carriage. DESIGN:
      Samples were obtained from neonates and their mothers 0 to 5 days after birth and
      again 3 weeks later. Clinical patterns of common acnelike pustulosis were
      reported as mild (<10 papulopustules), moderate (> or =10 papulopustules), or
      absent. Direct examination and culture of sample. Identification of yeasts was
      based on microscopic and physiologic criteria. SETTING: A maternity hospital and
      the pediatric dermatology unit of a university hospital. PARTICIPANTS:
      Consecutive series of 102 neonates and their mothers. MAIN OUTCOME MEASURES:
      Incidence of skin colonization and type of Malassezia species found in neonates
      and correlation with neonatal cephalic pustulosis (neonatal acne). RESULTS: At
      the first visit, 11 neonates and 36 mothers had cultures positive for Malassezia.
      Malassezia sympodialis and Malassezia globosa were preferentially cultured. At 3
      weeks, 29 (52%) of 56 neonates and 18 (32%) of 56 mothers had cultures positive
      for only M sympodialis and M globosa. Breastfeeding was not associated with a
      higher prevalence of Malassezia carriage in neonates. Malassezia colonization was
      higher when pustulosis was more severe and M sympodialis was found in pustules.
      CONCLUSIONS: Malassezia colonization begins at birth and increases in the first
      weeks of life. A high prevalence of M sympodialis in neonates is noted from
      birth. Its association with neonatal acne is confirmed. Further investigation is
      needed to study the role of sebum secretion rate and quality in the neonatal
      period.

PMID- 11843643
TI  - Comparative in vitro pediculicidal efficacy of treatments in a resistant head
      lice population in the United States.
AB  - OBJECTIVE: To compare the pediculicidal activity of 5 head lice products
      available in the United States on head lice from south Florida. DESIGN: In vitro
      pediculicidal product comparison. SETTING: Lice Source Services, Inc, located in
      Plantation, Fla, a clinic for the treatment and grooming of individuals with
      pediculosis capitis. PARTICIPANTS: Head lice were collected from healthy clients
      with Pediculus capitis that came to Lice Source Services, Inc, to seek their
      services. INTERVENTIONS: Within 2 to 6 hours of capture, lice were placed in
      continuous direct contact with the pediculicide products and observed at regular
      intervals. Results were compared with findings of a recent study of a treatment
      sensitive population of head lice conducted in Panama. MAIN OUTCOME MEASURE:
      Percentage of lice dead at regular observation intervals between 5 minutes and 3
      hours of continuous exposure to the pediculicides. RESULTS: Two prescription
      products, Ovide lotion (0.5% malathion) and 1% lindane shampoo, were ranked in
      the same order as in 2 previous studies (first and last, respectively). The order
      of effectiveness from most to least effective was as follows: Ovide lotion, A-200
      shampoo (a natural pyrethrin product synergized with piperonyl butoxide),
      undiluted Nix (1% permethrin), diluted Nix, RID (a natural pyrethrin product
      synergized with piperonyl butoxide), and 1% lindane shampoo. CONCLUSIONS: There
      were statistically significant differences in the efficacy of all the products
      when compared with the results found in the recent study in Panama, except for
      Ovide lotion. Of those tested, Ovide was the only pediculicide in the United
      States that had not become less effective. The difference in efficacy of 1%
      lindane, Nix, and pyrethrins between the Panama and Florida studies supports the
      argument that some head lice in the United States have become resistant to these
      treatments.

PMID- 11843644
TI  - Broad spectrum of dermatologic manifestations caused by Mycobacterium haemophilum
      infection.

PMID- 11843645
TI  - Herbal therapy in dermatology.
AB  - Herbal therapy is becoming increasingly popular among patients and physicians.
      Many herbal preparations are marketed to the public for various ailments
      including those of the skin. Herbal therapies have been used successfully in
      treating dermatologic disorders for thousands of years in Europe and Asia. In
      Germany, a regulatory commission oversees herbal preparations and recommended
      uses. In Asia, herbal treatments that have been used for centuries are now being
      studied scientifically. Currently, the United States does not regulate herbal
      products, as they are considered dietary supplements. Therefore, there is no
      standardization of active ingredients, purity, or concentration. There are also
      no regulations governing which herbs can be marketed for various ailments. This
      has made learning about and using these treatments challenging. Information
      compiled in a practical fashion may enable more patients to benefit from these
      treatments currently used worldwide. We reviewed the herbal medications that show
      scientific evidence of clinical efficacy, as well as the more common herbs shown
      to be useful in the treatment of dermatologic disorders. The safety of each herb
      has been addressed to better enable the physician to know which herbal therapies
      they may want to begin to use in practice. Common drug interactions and side
      effects of herbal medicines that may be seen in the dermatologic setting were
      also studied.

PMID- 11843646
TI  - Mycosis fungoides: new insights into an old problem.

PMID- 11843647
TI  - Opening the doors of perception: complementary approaches to dermatologic
      disease.

PMID- 11843648
TI  - Neonatal acne and cephalic pustulosis: is malassezia the whole story?

PMID- 11843649
TI  - Subcutaneous nodules in a patient with hydrocephalus.

PMID- 11843650
TI  - An unusual cause of hair loss.

PMID- 11843651
TI  - Persistent nodule on the nose.

PMID- 11843652
TI  - Itchy papules of the axillae.

PMID- 11843653
TI  - On first looking into Pernkopf's Atlas: some further comments.

PMID- 11843654
TI  - Compounding of topical cidofovir.

PMID- 11843655
TI  - Facial wrinkling and basal cell carcinoma.

PMID- 11843657
TI  - Drug hypersensitivity syndrome and human herpesvirus 6 reactivation.

PMID- 11843659
TI  - Toenail dystrophy with COL7A1 glycine substitution mutations segregates as an
      autosomal dominant trait in 2 families with dystrophic epidermolysis bullosa.

PMID- 11843660
TI  - Cutaneous infection showing sporotrichoid spread caused by Pseudallescheria
      boydii (Scedosporium apiospermum): successful detection of fungal DNA in formalin
      fixed, paraffin-embedded sections by seminested PCR.

PMID- 11843661
TI  - Cellular phone dermatitis.

PMID- 11843663
TI  - Response to cyclosporine in a patient with disseminated granuloma annulare
      associated with CD4+/CD8+(dim)/CD56+ large granular lymphocytic leukemia.

PMID- 11843662
TI  - Vitiligo and epidermal microenvironment: possible involvement of keratinocyte
      derived cytokines.

PMID- 11843664
TI  - Familial confluent and reticulated papillomatosis.

PMID- 11843669
TI  - Laser madness in facial plastic surgery.

PMID- 11843671
TI  - The versatility of distraction osteogenesis in craniofacial surgery.
AB  - OBJECTIVES: To review our preliminary results using distraction osteogenesis for
      the correction of craniofacial deformities and to determine its role in treating
      anatomic deformities and functional deficits relative to conventional
      craniofacial surgery. DESIGN AND SETTING: Retrospective clinical review; tertiary
      care center. METHODS: Twenty-four consecutive patients were treated with
      distraction osteogenesis during a 34-month period. Outcomes were compared with
      preexisting anatomic deformities and functional deficits using records of
      clinical assessments, photodocumentation, diagnostic imaging, and treatment
      planning aids. MAIN OUTCOME MEASURES: Distraction achieved vs planned distraction
      based on clinical and radiographic assessment, clinical status of functional
      deficits before and after treatment, and objective rating of aesthetic
      improvement. CONCLUSIONS: Preliminary results demonstrated good-to-excellent
      outcome in correcting facial skeletal deformity in 80% of patients. Functional
      outcomes included resolution or significant improvement of upper airway
      obstruction in 13 of 14 patients and correction of corneal exposure for all 5
      patients with preexisting exorbitism. Correction of malocclusion was less
      reliable. Problems related to the distraction devices, including failure of the
      advancement mechanism and fixation, were the most prevalent complications.
      Distraction osteogenesis represents an exciting new development in craniofacial
      surgery with several potential benefits, including less invasive surgery, the
      ability for earlier intervention, and the potential for correction of more severe
      deformities with improved posttreatment stability. The exact role of distraction
      osteogenesis relative to conventional techniques requires ongoing assessment.

PMID- 11843672
TI  - Elevation of the malar fat pad with a percutaneous technique.
AB  - OBJECTIVE: To describe a simplified method of malar fat pad elevation to
      rejuvenate the midface, nasolabial folds, labiomental folds, infraorbital
      hollows, and jowls via a percutaneous approach. PATIENTS AND DESIGN: One hundred
      eighteen patients were evaluated over a 12-month period in a prospective fashion
      by the operating surgeon. Preoperative and postoperative photographs were used
      for comparison. SETTING: Private practice. MAIN OUTCOME MEASURES: Elevation of
      the malar fat pad by a measured amount. RESULTS: At 3 months, all patients had a
      significant elevation of the malar fat pad (3-7 mm), with the exception of 2
      early patients who underwent revision surgery, with satisfactory results.
      CONCLUSIONS: A simplified method of malar fat pad elevation is described. This
      method allows for elevation of the malar fat pad without extensive dissection.
      Excellent results are obtained with very little morbidity.

PMID- 11843673
TI  - Correction of the soft tissue pollybeak using triamcinolone injection.
AB  - OBJECTIVE: To describe the technique for correction of the soft tissue pollybeak
      deformity using intralesional injection of triamcinolone acetonide. METHODS: We
      discuss our philosophy, regimen, and technique for treatment of the soft tissue
      pollybeak using triamcinolone injection. We include results from a series of 173
      patients who underwent rhinoplasty performed by one of us (N.J.P.). RESULTS:
      Triamcinolone was injected at 1 week after surgery in 127 patients (73%). A
      second injection was performed in 92 (72%) of the 127 patients at 4 weeks after
      surgery. One hundred eight (85%) of the 127 patients had an acceptable result, as
      judged by the surgeon, with good supratip definition. Nineteen (15%) of the 127
      patients had a less than optimal result, with residual supratip fullness, as
      judged by the surgeon. There were no complications caused by triamcinolone
      injection. CONCLUSIONS: Because revision surgery is difficult and may be
      associated with complications, intralesional triamcinolone injection is the first
      line treatment for the soft tissue pollybeak deformities caused by subdermal
      scarring. Should intralesional steroid injection fail to satisfactorily treat the
      deformity, revision rhinoplasty can subsequently be performed.

PMID- 11843675
TI  - The single-stage forehead flap in nasal reconstruction: an alternative with
      advantages.
AB  - OBJECTIVE: To review the single-stage forehead flap for patient selection,
      technique, and main outcome measures. METHODS: Patients undergoing nasal
      reconstruction between January 1, 1995, and June 30, 2000, were reviewed from
      medical records, photographs, and personal communication. All work was performed
      in an academic medical center. RESULTS: Fifty-one patients had a forehead flap
      for nasal reconstruction, of which 10 (20%) were repaired in a single stage. All
      patients had no evidence of small vessel disease, eg, hypertension, diabetes
      mellitus, or tobacco use. Nasal defects were limited to the upper two thirds of
      the nose. The technique is modified from the original description by creating a
      unilateral, subcutaneous pedicle, wide undermining, and partial resection of the
      procerus muscle. One patient had superficial epidermolysis at the distal tip of
      the flap. The remaining 9 patients maintained complete viability with
      satisfactory outcomes. One debulking procedure was performed to the glabellar
      area for aesthetic reasons. The average interval for returning to work was 6.6
      days compared with the minimal 3 weeks for conventional interpolated flaps.
      CONCLUSION: In select cases, a single-stage, island midline forehead flap can be
      used safely as an advantageous alternative to the conventional interpolated
      forehead flap.

PMID- 11843676
TI  - Subdermal carbon dioxide laser cutaneous contraction.
AB  - BACKGROUND: Conventional carbon dioxide (CO(2)) skin laser resurfacing reverses
      the effects of photoaging. A recent clinical series reported the efficacy of
      performing subdermal CO(2)resurfacing to obtain the same skin contracture as
      epidermal skin resurfacing. OBJECTIVE: To assess surface area contraction that
      occurs with subdermal CO(2) laser resurfacing in the rat model. DESIGN: A
      nonrandomized control study was performed using 32 rats. The 3 test groups were
      divided by CO(2) laser strength (5 vs 7 W) and the pattern of resurfacing (cross
      hatched vs parallel lines). MATERIALS AND METHODS: The rats underwent subdermal
      continuous 2-mm defocused CO(2)beam treatment of the right-sided experimental
      flap. The left subdermal flap acted as a control. In the first group (n = 12), a
      subdermal cross-hatching of the subdermal flap was performed with 7 W. The second
      group (n = 10) was resurfaced in a parallel fashion with 7 W. The third group (n
      = 10) was resurfaced in a parallel fashion with 5 W. Measurements of skin area
      were taken immediately after laser resurfacing and 3 weeks after the treatment.
      RESULTS: None of the treatment arms showed a change in skin surface area
      immediately or 3 weeks after treatment. In the first treatment group, all of the
      treated flaps showed an entire full-thickness slough. Of the controls, 75% showed
      minimal sloughing. The second and third experimental groups showed a 100% slough
      of the flaps. Of the 20 control flaps in the second and third groups, only 1 had
      a partial slough. CONCLUSIONS: In this animal model, subdermal CO(2) laser
      resurfacing showed a 100% rate of skin sloughing. No change in skin surface area
      was evident immediately or 3 weeks after treatment.

PMID- 11843678
TI  - Reconstruction of the nasal columella.
AB  - OBJECTIVE: To report techniques successful for nasal columella reconstruction.
      METHODS: Retrospective medical chart review of patients undergoing columella
      reconstruction by 2 of us (D.A.S. and P.A.H.) from January 1, 1982, to December
      31, 2000. Photographs before tumor resection or trauma, after resection or
      trauma, and after reconstruction were examined by facial plastic surgeons masked
      to the cases and were rated on a 10-cm visual analogue scale. RESULT: Sixteen
      patients were identified, most of whom had columellar defects repaired with
      forehead flaps, nasolabial flaps, or nasofacial sulcus flaps. The mean
      improvement on the 10-cm visual analogue scale was 2.0 from before tumor
      resection or trauma to after reconstruction, and 5.0 from tumor resection or
      trauma to after reconstruction. CONCLUSION: Skin grafts, composite grafts, and
      several flaps, including nasolabial, nasofacial sulcus, and forehead flaps, are
      useful in repairing defects of the nasal columella.

PMID- 11843679
TI  - Biplanar plating of mandibular fractures: a new concept with in vitro testing and
      comparison with the traditional plate-and-screw technique.
AB  - OBJECTIVES: To introduce the concept of biplanar plating of mandibular fractures
      and to present an in vitro comparison of this method with traditional use of a
      single mandibular plate. DESIGN: A device for the delivery of repetitive
      simulated masticatory stress to mandibular models was developed. Using the
      device, we compared biplanar with single-plate fixation of vertical mandibular
      body fractures by determining cycles to failure. SETTING: Tertiary care academic
      medical center. INTERVENTION: A simulated masticatory force was delivered
      vertically to the anterior end of polymer hemimandibles as used for in vitro
      teaching of plating methods. Mobility at the fracture site was tested at
      intervals corresponding to 6000 chewing cycles each. RESULTS: Of 5 specimens
      plated with a mandibular fixation plate, 4 developed greater than 0.010 cm of
      vertical mobility at the fracture site after 12 000 cycles. Only 1 of the 5
      specimens fixed with biplanar plating developed this degree of mobility.
      CONCLUSIONS: Single-plate fixation of mandibular fractures is greatly enhanced by
      a miniplate spanning the fracture along the inferior border. We used this
      technique on 15 patients with unfavorable fractures and found it simple, secure,
      and reliable. We had no complications. An inferior marginal plate serves the same
      function as a tension band, and can be placed on mandibles through the same
      incision as the main fixation plate without additional dissection. We prefer this
      to a traditional tension band when the percutaneous route of access to a
      mandibular fracture site is used.

PMID- 11843680
TI  - Middle-vault narrowing in the wide nasal dorsum: the "Reverse Spreader"
      technique.
AB  - The middle vault is a transition zone between the nasal tip and nasal bones and
      plays an important role in profile, tip projection, tip rotation, and tip
      support. This report presents an alternative to conventional techniques specific
      to the middle nasal vault for a patient population with particular nasal
      features. A narrow middle vault with internal nasal valve collapse is
      functionally and aesthetically addressed by the insertion of spreader grafts.
      However, the inverse of this situation is sometimes encountered. A patient with a
      broad middle vault and without internal nasal valve collapse will benefit from
      reduction of the horizontal width of the cartilaginous dorsum, which is in effect
      the reverse of spreader grafts. This effect is achieved by excising a vertical
      wedge-shaped strip of cartilage that follows the length of the upper lateral
      cartilage at the junction of the upper lateral cartilage and the dorsal nasal
      septum.

PMID- 11843683
TI  - The Farrior lineage: opening address given at the First Annual Richard T. Farrior
      Course on Facial Plastic Surgery.

PMID- 11843684
TI  - Prospective evaluation of eyelid function with gold weight implant and lower
      eyelid shortening for facial paralysis.

PMID- 11843685
TI  - Correlation of preoperative computed tomography and postoperative ocular motility
      in orbital blowout fractures.

PMID- 11843688
TI  - Refractory status epilepticus in 2001.

PMID- 11843689
TI  - Poststroke seizures.
AB  - Stroke is the most common cause of seizures in the elderly, and seizures are
      among the most common neurologic sequelae of stroke. About 10% of all stroke
      patients experience seizures, from stroke onset until several years later. This
      review discusses current understanding of the epidemiology, pathogenesis,
      classification, clinical manifestations, diagnostic studies, differential
      diagnosis, and management issues of seizures associated with various
      cerebrovascular lesions, with a focus on anticonvulsant use in the elderly.

PMID- 11843690
TI  - Refractory status epilepticus: frequency, risk factors, and impact on outcome.
AB  - BACKGROUND: Refractory status epilepticus (RSE) is a life-threatening condition
      in which seizures do not respond to first- and second-line anticonvulsant drug
      therapy. How often RSE occurs, risk factors that predispose to this condition,
      and the effect of failure to control seizures on clinical outcome are poorly
      defined. OBJECTIVE: To determine the frequency, risk factors, and impact on
      outcome of RSE. DESIGN: Retrospective cohort study. SETTING: Large academic
      teaching hospital. PATIENTS: Consecutive sample of 83 episodes of status
      epilepticus in 74 patients (mean age, 63 years). MAIN OUTCOME MEASURES:
      Refractory status epilepticus was defined as seizures lasting longer than 60
      minutes despite treatment with a benzodiazepine and an adequate loading dose of a
      standard intravenous anticonvulsant drug. Factors associated with RSE were
      identified using univariate and backward stepwiselogistic regression analyses.
      RESULTS: In 57 episodes (69%), seizures occurred after treatment with a
      benzodiazepine, and in 26 (31%), seizures occurred after treatment with a second
      line anticonvulsant drug (usually phenytoin), fulfilling our criteria for RSE.
      Nonconvulsive SE (P=.03) and focal motor seizures at onset (P=.04) were
      identified as independent risk factors for RSE. Eleven (42%) of 26 patients with
      RSE had seizures after receiving a third-line agent (usually phenobarbital).
      Although mortality was not increased (17% overall), RSE was associated with
      prolonged hospital length of stay (P<.001) and more frequent functional
      deterioration at discharge (P=.02). CONCLUSIONS: Refractory status epilepticus
      occurs in approximately 30% of patients with SE and is associated with increased
      hospital length of stay and functional disability. Nonconvulsive SE and focal
      motor seizures at onset are risk factors for RSE. Randomized controlled trials
      are needed to define the optimal treatment of RSE.

PMID- 11843691
TI  - Reduction of plasma 24S-hydroxycholesterol (cerebrosterol) levels using high
      dosage simvastatin in patients with hypercholesterolemia: evidence that
      simvastatin affects cholesterol metabolism in the human brain.
AB  - BACKGROUND: Previous studies have shown that patients with early onset of
      Alzheimer disease and vascular dementia have higher levels of circulating brain
      derived 24S-hydroxycholesterol (cerebrosterol). Two recent epidemiological
      studies indicated that treatment with inhibitors of cholesterol synthesis
      (statins) reduces the incidence of Alzheimer disease. OBJECTIVE: To test the
      hypothesis that treatment with high-dosage simvastatin reduces circulating levels
      of 24S-hydroxycholesterol. DESIGN: Prospective, 24-week treatment trial for
      lowering of cholesterol levels. We conducted assessments at baseline, week 6, and
      week 24. SETTING: An academic outpatient clinical study. PATIENTS: Eighteen
      patients who met the criteria for hypercholesterolemia. INTERVENTION: Treatment
      with 80 mg/d of simvastatin at night. MAIN OUTCOME MEASURES: Plasma lipoprotein
      levels were measured enzymatically; lathosterol, by means of gas chromatography;
      and 24S-hydroxycholesterol, by means of gas chromatography-mass spectrometry.
      RESULTS: Simvastatin reduced total plasma cholesterol levels by 36% and 35% after
      6 and 24 weeks, respectively (P<.001). Lathosterol levels were reduced by 74% and
      72%, respectively, and the ratio of lathosterol to cholesterol, an indicator of
      whole-body cholesterol synthesis, was reduced by 60% and 61%, respectively
      (P<.001). Plasma 24S-hydroxycholesterol levels were lowered by 45% and 53%,
      respectively (P<.001). The ratio of 24S-hydroxycholesterol to cholesterol also
      decreased significantly (-12% [P=.01] and -23% [P<.002], respectively). The
      further reduction of 24S-hydroxycholesterol levels and its ratio to cholesterol
      from weeks 6 to 24 was also significant (P=.02 for both). CONCLUSIONS: The
      greater reduction of plasma concentrations of 24S-hydroxycholesterol compared
      with cholesterol indicates that simvastatin in a dosage of 80 mg/d reduces
      cholesterol turnover in the brain. The present results might describe a possible
      mechanism of how long-term treatment with statins could reduce the incidence of
      Alzheimer disease.

PMID- 11843692
TI  - A controlled prospective study of neuropsychological dysfunction following
      carotid endarterectomy.
AB  - BACKGROUND: Although subtle cognitive injury as revealed by neuropsychological
      testing occurs in a substantial number of patients following carotid
      endarterectomy (CEA), there is controversy about whether this finding is a result
      of the surgery or the anesthesia. OBJECTIVES: To examine the changes in
      neuropsychological test performance in patients following CEA vs a control group
      of patients older than 60 years following spine surgery, so as to determine
      whether neuropsychological dysfunction after CEA is a result of surgery or
      anesthesia. METHODS: Patients undergoing CEA (n = 80) and lumbar spine surgery (n
      = 25) were assessed with a battery of neuropsychological tests preoperatively and
      on postoperative days 1 and 30. The neuropsychological performance of patients in
      the control group was used to normalize performance for patients in the CEA
      group, by calculating z scores using the mean and SD of the change scores in the
      control group. Significant cognitive dysfunction was defined as performance that
      exceeded 2 SDs above the mean performance of patients in the control group.
      RESULTS: Postoperative days 1 and 30 total deficit scores were significantly
      worse in the CEA group compared with the controls. When individual test results
      were examined, the CEA group performed significantly worse than the controls on
      the Rey Complex Figure test and Halstead-Reitan Trails B on day 1, and on the Rey
      Complex Figure on day 30. Overall, cognitive dysfunction was seen in 22 patients
      (28%) in the CEA group on day 1 and in 11 (23%) of 48 patients on day 30.
      CONCLUSIONS: Subtle cognitive decline following CEA occurs and persists for at
      least several weeks after surgery. This decline was absent in a control group.

PMID- 11843693
TI  - Use of lipid-lowering agents, indication bias, and the risk of dementia in
      community-dwelling elderly people.
AB  - BACKGROUND: Recent reports suggest a possibly protective effect for statins in
      patients with Alzheimer disease. This association could be due to indication
      bias, i.e., people who elect to take lipid-lowering agents (LLAs) may be
      healthier than those who do not, so that it may be these other health factors
      that explain their lower risk of dementia. OBJECTIVES: To examine the association
      between the use of LLAs and dementia, adjusting for other markers of health, and
      to investigate factors associated with LLA use. DESIGN: A cohort study of LLA use
      and a case-control study of dementia in relation to LLA use, in a secondary
      analysis of the Canadian Study of Health and Aging. SETTING: A nationally
      representative population-based survey of Canadians 65 years and older.
      PARTICIPANTS: To examine features associated with statin use, we evaluated data
      on 2305 people for whom health information, drug use, and cognitive status were
      known. To examine the relationship between LLA use and dementia, we selected
      incident cases of dementia (n = 492, of whom 326 had Alzheimer disease) that
      occurred between the first and second waves of the study. Control subjects were
      823 persons examined during the first and second phases of the Canadian Study of
      Health and Aging who had no cognitive impairment. RESULTS: Use of LLAs was
      significantly (P<.001) more common in younger (65-79 years) than in older (> or =
      80 years) people. It was not associated with other factors indicating a healthy
      lifestyle, but was associated with a history of smoking and hypertension. Use of
      statins and other LLAs reduced the risk of Alzheimer disease in subjects younger
      than 80 years, an effect that persisted after adjustment for sex, educational
      level, and self-rated health (odds ratio, 0.26; 95% confidence interval, 0.08
      0.88). There was no significant effect in subjects 80 years and older.
      CONCLUSIONS: While the possibility of indication bias in the original
      observations cannot be excluded, it was not demonstrated in LLA use in this
      study. Lipid-lowering agent use was associated with a lower risk of dementia, and
      specifically of Alzheimer disease, in those younger than 80 years. Further
      research is warranted.

PMID- 11843694
TI  - Clinical and radiological correlates of reduced cerebral blood flow measured
      using magnetic resonance imaging.
AB  - BACKGROUND: Methods for determining cerebral blood flow (CBF) using bolus
      tracking magnetic resonance imaging (MRI) have recently become available. Reduced
      apparent diffusion coefficient (ADC) values of brain tissue are associated with
      reductions in regional CBF in animal stroke models. OBJECTIVES: To determine the
      clinical and radiological features of patients with severe reductions in CBF on
      MRI and to analyze the relationship between reduced CBF and ADCs in acute
      ischemic stroke. DESIGN: Case series. SETTING: Referral center. METHODS: We
      studied 17 patients with nonlacunar acute ischemic stroke in whom perfusion
      weighted imaging (PWI) and diffusion-weighted imaging (DWI) were performed within
      7 hours of symptom onset. A PWI-DWI mismatch of more than 20% was required. We
      compared patients with ischemic lesions that had CBF of less than 50% relative to
      the contralateral hemisphere with patients with lesions that had relative CBF
      greater than 50%. Characteristics analyzed included age, time to MRI, baseline
      National Institutes of Health Stroke Scale score, mean ADC, DWI and PWI lesion
      volumes, and 1-month Barthel Index score. RESULTS: Patients with low CBF (n = 5)
      had lower ADC values (median, 430 x 10 (-6) mm(2)/s vs. 506 x 10 (-6) mm(2)/s; P
      =.04), larger DWI volumes (median, 41.8 cm(3) vs. 14.5 cm(3); P =.001) and larger
      PWI lesions as defined by the mean transit time volume (median, 194.6 cm(3) vs.
      69.3 cm(3); P =.01), and more severe baseline National Institutes of Health
      Stroke Scale scores (median, 15 vs. 9; P =.02). CONCLUSION: Ischemic lesions with
      severe CBF reductions, measured using bolus-tracking MRI, are associated with
      lower mean ADCs, larger DWI and PWI volumes, and higher National Institutes of
      Health Stroke Scale scores.

PMID- 11843696
TI  - Irreversible disability and tissue loss in multiple sclerosis: a conventional and
      magnetization transfer magnetic resonance imaging study of the optic nerves.
AB  - OBJECTIVES: To assess, by magnetic resonance imaging, the volumes and
      magnetization transfer ratio (MTR) values of optic nerves (ONs) from patients
      with multiple sclerosis (MS) who had incomplete or no visual recovery after optic
      neuritis; and to compare these quantities with those derived from ONs from
      patients with MS who showed a marked clinical recovery after optic neuritis, ONs
      from healthy volunteers, and ONs from patients with Leber hereditary optic
      neuropathy (LHON). METHODS: Conventional and magnetization transfer magnetic
      resonance images of the ONs were obtained from 30 patients with MS, 18 healthy
      volunteers, and 10 patients with LHON. The ON from patients with MS were
      classified as clinically unaffected (n = 18); clinically affected with recovery
      (n = 20; visual acuity > or =20/25 at least 6 months after optic neuritis); and
      clinically affected with incomplete or no recovery (n = 22; visual acuity <20/25
      at least 6 months after optic neuritis). The ON volumes and MTR values were
      measured. RESULTS: Volumes (P =.002) and MTR values (P<.001) of the ONs from
      patients with MS and incomplete or no recovery were both lower than those of the
      ONs from patients with MS and recovery, but not different from those of the ONs
      from patients with LHON. Volumes and MTR values of the affected ONs from patients
      with MS and recovery did not differ from those of clinically unaffected ONs,
      which were similar to those of healthy volunteers. CONCLUSION: These findings
      suggest that, in patients with MS, neurodegeneration is associated with
      persistent functional deficits secondary to incomplete recovery from relapses.

PMID- 11843695
TI  - Progression of corpus callosum atrophy in Alzheimer disease.
AB  - BACKGROUND: Atrophy of the corpus callosum in the absence of primary white matter
      degeneration reflects loss of intracortical projecting neocortical pyramidal
      neurons in Alzheimer disease (AD). OBJECTIVES: To determine individual rates of
      atrophy progression of the corpus callosum in patients with AD and to correlate
      rates of atrophy progression with clinical disease severity and subcortical
      disease. METHODS: Magnetic resonance imaging-derived measurements of corpus
      callosum size were studied longitudinally in 21 patients clinically diagnosed as
      having AD (mean observation time, 17.0 +/- 8.5 months) and 10 age- and sex
      matched healthy controls (mean observation time, 24.1 +/- 6.8 months). RESULTS:
      Corpus callosum size was significantly reduced in AD patients at baseline. Annual
      rates of atrophy of total corpus callosum, splenium, and rostrum were
      significantly larger in AD patients (-7.7%, -12.1%, and -7.3%, respectively) than
      in controls (-0.9%, -1.5%, and 0.6%, respectively). Rates of atrophy of the
      corpus callosum splenium were correlated with progression of dementia severity in
      AD patients (rho = 0.52, P<.02). The load of subcortical lesions at baseline
      (P<.05) predicted rate of anterior corpus callosum atrophy in healthy controls.
      Rates of atrophy of corpus callosum areas were independent of white matter
      hyperintensity load in patients with AD. CONCLUSIONS: Measurement of corpus
      callosum size allows in vivo mapping of neocortical neurodegeneration in AD over
      a wide range of clinical dementia severities and may be used as a surrogate
      marker for evaluation of drug efficacy.

PMID- 11843697
TI  - Middle cerebral artery stenosis is a major clinical determinant in
      striatocapsular small, deep infarction.
AB  - BACKGROUND: The significance of the stenotic lesions of the middle cerebral
      artery (MCA) in Asian patients with striatocapsular small, deep infarctions
      (SSDIs) remains undetermined. OBJECTIVES: To investigate the frequency of
      stenotic lesions of the MCA in patients with SSDIs and to evaluate clinical and
      radiological features in those same patients. SETTING: Acute stroke registry of a
      university hospital. PATIENTS AND METHODS: One hundred two Korean patients with
      acute symptomatic SSDIs underwent cerebral angiography or magnetic resonance
      angiography and echocardiography. We divided these patients into 2 groups
      patients with and without MCA occlusive lesions. The clinical and magnetic
      resonance image features were compared between these 2 groups. RESULTS: Thirty
      seven patients (36%) had an ipsilateral proximal MCA lesion, whereas 65 patients
      (64%) showed no MCA abnormality on cerebral angiography or magnetic resonance
      angiography. Among 65 patients without an MCA lesion, 18 had an embolic source;
      the remaining 37 patients had no demonstrable embolic source. There were
      significant differences in the temporal profile and magnetic resonance imaging
      findings between the groups. Although the type of lacunar syndrome and the volume
      of infarcts did not differ between the groups, the unstable temporal profile and
      magnetic resonance imaging findings of multiple small infarcts in the symptomatic
      hemisphere were frequently observed in patients with MCA lesions. CONCLUSIONS:
      The proximal MCA lesion was a common cause of SSDIs in Korean patients. Depending
      on the existence of an MCA lesion, the clinical course and magnetic resonance
      imaging feature of the patients with SSDIs were different.

PMID- 11843698
TI  - Biochemical-clinical correlation in patients with different loads of the
      mitochondrial DNA T8993G mutation.
AB  - OBJECTIVE: To investigate the correlation between biochemical and clinical
      phenotype in 6 patients from 3 unrelated families with different mutation loads
      (heteroplasmy) of the T8993G mitochondrial DNA mutation associated with
      neuropathy, ataxia, and retinitis pigmentosa-Leigh syndrome. METHODS: We studied
      adenosine triphosphate (ATP) synthase activity (synthesis and hydrolysis) in
      platelet-derived submitochondrial particles and assessed mutant loads both in
      platelets used for biochemical analysis and in other available tissues.
      Biochemical and molecular results were correlated with clinical features.
      RESULTS: The rate of ATP hydrolysis was normal, but ATP synthesis was severely
      impaired (30% to 4% of residual activity) in patients harboring 34% to 90% mutant
      mitochondrial DNA, without any evidence of a threshold for the expression of this
      defect. There was little variation in heteroplasmy among tissues from each
      patient, but wider variability was detected in 2 mothers. Correlation of
      heteroplasmy and clinical and biochemical features suggested that ATP synthesis
      is defective at mutant loads as low as 34% and is extremely reduced at mutant
      loads above 80% when the phenotype is neuropathy, ataxia, and retinitis
      pigmentosa-Leigh syndrome. CONCLUSIONS: This study indicates a close relationship
      between tissue heteroplasmy, expression of the biochemical defect in platelets,
      and clinical involvement. The biochemical defect was greater than previously
      reported, and we found no evidence of a biochemical threshold. The uniform
      distribution of high mutant loads among our patients' tissues suggests a
      differential tissue-specific reliance on mitochondrial ATP synthesis.

PMID- 11843699
TI  - Bicaudate ratio as a magnetic resonance imaging marker of brain atrophy in
      multiple sclerosis.
AB  - CONTEXT: Brain atrophy has emerged as a useful surrogate marker of disease
      involvement in multiple sclerosis (MS). The relationship between whole-brain or
      regional atrophy and cognitive dysfunction is poorly understood. OBJECTIVES: To
      determine whether the bicaudate ratio (BCR)-the minimum intercaudate distance
      divided by brain width along the same line-is increased in MS and to compare the
      ability of the BCR, whole-brain atrophy, and other magnetic resonance imaging
      markers to predict cognitive dysfunction. DESIGN: Case-control study. SETTING:
      University-affiliated clinic. PARTICIPANTS: Sixty patients with MS and 50 age-
      and sex-matched control subjects. MAIN OUTCOME MEASURES: Bicaudate ratio, whole
      brain atrophy, T2 lesion load, T1 ("black hole") lesion load, and caudate volume
      were measured quantitatively using fluid-attenuated inversion recovery, T1
      weighted, and gradient-echo magnetic resonance imaging scans. Symbol Digit
      Modalities Test was used to assess cognitive function. RESULTS: The BCR (mean
      [SD]) was higher in patients with MS (0.11 [0.03]) than in controls (0.09 [0.02])
      (P<.001), suggesting subcortical atrophy in MS. The BCR was related to total T2
      (r = 0.56, P<.001) and T1 (r = 0.40, P<.002) lesion volumes, but not caudate
      volume in patients with MS. Regression modeling selected BCR (P<.05), but not
      whole-brain atrophy, T1 or T2 lesion volume, or caudate volume as predictive of
      Symbol Digit Modalities Test score in patients with MS. CONCLUSIONS: The BCR is
      increased in MS and is more closely associated with cognitive dysfunction than
      are other magnetic resonance imaging surrogate markers including whole-brain
      atrophy. Increased BCR is best explained by frontal horn ventricular enlargement
      due to atrophy of deep frontal subcortical white matter. This highlights the
      close relationship between subcortical atrophy and cognitive impairment in
      patients with MS.

PMID- 11843700
TI  - Spectrum of SPG4 mutations in a large collection of North American families with
      hereditary spastic paraplegia.
AB  - BACKGROUND: Hereditary spastic paraplegia (HSP) is a neurodegenerative disease
      characterized by progressive spasticity and weakness of the lower limbs. The most
      common form of HSP is caused by mutations in the SPG4 gene, which codes for
      spastin, an adenosine triphosphatase with various cellular activities (AAA)
      protein family member. OBJECTIVE: To investigate a large collection of
      predominantly North American patients with HSP for mutations in the spastin
      encoding gene, SPG4. METHODS: DNA from 76 unrelated affected individuals was
      studied for mutations by single-stranded conformational polymorphism analysis and
      direct sequencing. Each new variant identified was then analyzed in 80 control
      subjects to determine whether the variant is a common polymorphism or a rare
      mutation. All DNA samples were amplified by polymerase chain reaction, followed
      by electrophoresis and autoradiography. RESULTS: We identified 8 novel mutations
      and 5 previously reported mutations in 15 affected individuals. The novel
      mutations are 4 missense, 1 nonsense, 1 frameshift, and 2 splice mutations. Two
      polymorphisms (one in an affected individual) were also identified. CONCLUSIONS:
      Our collection of families with HSP is different on a genetic level from those
      previously described. The percentage of our families with a SPG4 mutation is 10%
      lower than the 40% estimate of families with autosomal dominant HSP noted to be
      linked to this locus, and splice mutations are not predominant in our collection.
      Interestingly, we also identified 2 recurring mutations in specific populations
      (R562Q and G559D), which may facilitate the development of future spastin
      diagnostic testing in these populations.

PMID- 11843701
TI  - Corneal endothelial degeneration in dentatorubral-pallidoluysian atrophy.
AB  - BACKGROUND: Dentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal dominant
      spinocerebellar degeneration that exhibits a variety of neurologic
      manifestations. However, only a few reports have studied disturbances outside the
      central nervous system. We described 2 unrelated patients with DRPLA accompanied
      by corneal endothelial degeneration. PATIENTS AND METHODS: A 52-year-old man
      presented with cerebellar ataxia and dementia. Magnetic resonance imaging of the
      brain showed cerebellar atrophy. Dentatorubral-pallidoluysian atrophy was
      diagnosed because of the detection of expansion of CAG repeats at the DRPLA
      locus. On admission, his visual acuity was severely impaired. Specular microscopy
      showed decreased endothelial cell density (500 cells/mm(2)) compared with that of
      healthy subjects. The second patient was a 69-year-old man with cerebellar
      ataxia. Magnetic resonance imaging of the brain showed cerebellar and brainstem
      atrophy. The diagnosis of DRPLA was based on expanded CAG repeats of the DRPLA
      gene. Specular microscopy showed significant decrease of endothelial cell density
      (1506 cells/mm(2)). Reverse transcriptase-polymerase chain reaction analysis
      showed DRPLA gene expression in corneal endothelial cells. CONCLUSIONS: Mutant
      DRPLA protein may be directly associated with corneal endothelial degeneration.
      Corneal endothelial cell loss is an important sign of DRPLA, and the corneas of
      patients with DRPLA should be examined.

PMID- 11843702
TI  - Intrafamilial phenotypic variability in Friedreich ataxia associated with a G130V
      mutation in the FRDA gene.
AB  - BACKGROUND: Most patients with Friedreich ataxia (FA) have a GAA trinucleotide
      repeat expansion in intron 1 of the FA gene (FRDA) on both arms of chromosome 9.
      However, some patients are compound heterozygotes and harbor a GAA expansion on
      one allele and a point mutation on the other. Compound heterozygous patients with
      FA who have a GAA expansion and a G130V mutation have been reported to have an
      atypical phenotype with a slow disease progression, minimal or no ataxia, or gait
      spasticity. OBJECTIVE: To describe intrafamilial phenotypic variability in a GAA
      expansion/G130V mutation compound heterozygous family with FA. SETTING: Tertiary
      referral university hospital setting. PATIENTS AND METHODS: A 34-year-old man
      presented to our hospital with a 24-year history of stiff legs and mild
      unsteadiness of gait. Clinical examination showed a spastic paraparesis with
      normal to pathologically brisk deep tendon reflexes and mild left upper limb
      ataxia. His 27-year-old sister presented with a slowly progressive early-onset
      ataxic syndrome. She had ataxia of gait, mild to severe limb ataxia, and reduced
      or absent deep tendon reflexes, but no evidence of spasticity on examination.
      RESULTS: Neurophysiologic investigations showed evidence of a sensory axonal
      neuropathy, and molecular genetic analysis showed that both siblings were
      compound heterozygotes with a GAA expansion and a G130V mutation. CONCLUSIONS:
      This report confirms that compound heterozygous patients with FA who have a GAA
      expansion and a G130V mutation may present with an ataxic phenotype and that
      intrafamilial phenotypic variability in these pedigrees can occur. It also
      emphasizes the importance of performing molecular genetic analysis for the GAA
      trinucleotide expansion in patients presenting with a spastic paraparesis of
      undetermined etiology, especially when there is neurophysiologic evidence of a
      sensory axonal neuropathy.

PMID- 11843703
TI  - Medical hypothesis: why secondary progressive multiple sclerosis is a
      relentlessly progressive illness.
AB  - Secondary progressive multiple sclerosis is a relentlessly progressive, usually
      ascending, disease process. Once secondary progression begins, regardless of how
      long the disease was present before secondary progression began, patients appear
      to progress at a uniform rate. Recent studies show that it responds poorly to
      medications effective in relapsing remitting disease, although these drugs
      decrease relapses and have a substantial effect on lesions seen on magnetic
      resonance imaging. Disruption of axonal transport is known to occur in
      demyelinated fibers. Synapses, vacated when axons are destroyed, cause sprouting
      in surviving terminal axons, resulting in metabolic overload in the terminal
      axons. This noninflammatory process would not be expected to be altered by
      current disease-altering therapies.

PMID- 11843704
TI  - Uncal herniation in acute subdural hematoma: point of no return.

PMID- 11843705
TI  - Sural nerve without nerve fibers in leprous neuropathy.

PMID- 11843706
TI  - Five hundred years of brain images.

PMID- 11843707
TI  - Attention-deficit/hyperactivity disorder.

PMID- 11843708
TI  - Infantile spasms: West syndrome.
AB  - West syndrome is an epileptic syndrome with a devastating clinical course. In
      recent years, anatomic and functional neuroimaging studies have helped to
      diagnose the cause of the spasms in most children, but with little progress in
      improving the poor developmental outcome associated with this syndrome. This
      article cites 4 seminal observations regarding the clinical presentation,
      diagnosis, and treatment of infantile spasms.

PMID- 11843718
TI  - Physician specialty is associated with differences in the evaluation and
      management of acute bacterial rhinosinusitis.
AB  - BACKGROUND: Acute bacterial rhinosinusitis (ABRS) is a common illness that is
      routinely managed by physicians from several different specialties. However, the
      actual diagnostic and treatment preferences of physicians from these different
      specialties are not known. OBJECTIVE: To determine whether the radiographic
      evaluation and management of community-acquired ABRS differs according to medical
      specialty. DESIGN, SETTING, AND PARTICIPANTS: Randomized survey of 450 board
      certified physicians in the United States from family medicine, general internal
      medicine, and otolaryngology. MAIN OUTCOME MEASURES: Responding physicians' use
      of diagnostic radiography as well as choice and duration of antimicrobial and
      adjunctive treatments of ABRS. RESULTS: Otolaryngologists were more likely to use
      supportive diagnostic radiography (P =.04). They were also more likely to treat
      patients with adjunctive therapy, such as topical decongestants (P =.01),
      guaifenesin (P =.01), and saline nasal irrigation (P =.01), in addition to
      antibiotics. Otolaryngologists prescribed more medications to treat patients with
      ABRS than primary care physicians (P =.01). There were no significant differences
      in diagnosis and management by family physicians and general internists.
      CONCLUSIONS: Otolaryngologists use more health care resources to diagnose and
      treat ABRS than primary care physicians despite an absence of evidence that such
      tests and treatments lead to better outcomes. Otolaryngologists typically treat a
      patient population with a higher prevalence of ABRS and frequently see referred
      patients with recurrent acute sinusitis and chronic rhinosinusitis, which may
      explain their tendency to treat patients more aggressively. Nevertheless, these
      survey results illustrate a lack of consensus within the medical community
      regarding the evaluation and management of community-acquired ABRS, suggesting
      that widely accepted evidence-based practice guidelines need to be developed.

PMID- 11843719
TI  - Expression of ICAM-1 in nasal epithelium and levels of soluble ICAM-1 in nasal
      lavage fluid during human experimental rhinovirus infection.
AB  - Most rhinovirus serotypes use intercellular adhesion molecule-1 (ICAM-1) as the
      receptor to enter cells, but ICAM-1 expression has not been detected on normal
      nasal epithelial cells. During experimental rhinovirus infection, expression of
      ICAM-1 on nasal epithelial cells was examined with immunohistochemical staining
      of nasal scrape biopsy specimens, and levels of soluble ICAM-1 in nasal lavage
      fluid were measured by sandwich enzyme-linked immunosorbent assay technique.
      Expression of ICAM-1 on nasal epithelial cells increased following inoculation in
      20 of 23 infected subjects. The median number of ICAM-1-positive cells per 6.25
      mm(2) area of stained biopsy specimen was 0 in control samples (day 20 or 33
      after inoculation), and in those without infection, 6 on day 1 (P< or =.05), 14.5
      on day 3 (P< or =.01), 1.5 on day 5, and 0 on day 9. In a different group of
      volunteers, soluble ICAM-1 in nasal lavage fluid was higher on days 1 and 3
      compared with preinoculation levels (P< or =.001), but only 11 of 23 infected
      subjects had a 2-fold or greater increase. Up-regulation of ICAM-1 receptor
      expression on nasal epithelial cells occurred within 24 hours after inoculation
      in experimental rhinovirus infections (prior to onset of symptoms) and declined
      promptly by day 5.

PMID- 11843720
TI  - Postendoscopic Zenker esophagodiverticulostomy leaks associated with a specific
      stapler cartridge.
AB  - OBJECTIVE: To determine the cause of postoperative leaks in 2 patients with
      Zenker diverticula treated with endoscopic staple-assisted
      esophagodiverticulostomy. DESIGN: Medical chart review and simulated surgery.
      SETTING: Teaching hospital. PATIENTS AND METHODS: Two case reports of
      postoperative leaks in patients treated with endoscopic staple-assisted
      esophagodiverticulostomy and experimental simulated surgery to investigate the
      possible cause of this complication. Use of a TR45B, 3.5-mm cartridge for an
      Endopath ETS Flex45 Endoscopic Articulation Linear Cutter stapler was associated
      with complications, whereas use of a TR45W, 2.5-mm cartridge in the same stapler
      was not. RESULTS: In a simulated surgery model, the 3.5-mm cartridge staple line
      leaked from the incision apex with pressure of less than 20 cm H(2)O, whereas the
      apex remained dry when using the 2.5-mm cartridge. When pressure was increased to
      30 cm H(2)O, the staple line of the 2.5-mm cartridge had diffuse weeping of fluid
      but no focal, apical leak. CONCLUSIONS: Endoscopic staple-assisted
      esophagodiverticulostomy continues to be a relatively safe procedure; however, to
      provide maximum safety at the apex, the surgeon needs to be aware of stapler
      cartridge differences.

PMID- 11843721
TI  - Endoscopic stapling technique for the treatment of Zenker diverticulum vs
      standard open-neck technique: a direct comparison and charge analysis.
AB  - BACKGROUND: Presently, the 2 most widely used methods for the treatment of Zenker
      diverticulum are endoscopic stapling of the common party wall between the
      diverticulum sac and the esophagus and the standard open-neck technique involving
      diverticulectomy and cricopharyngeal myotomy. OBJECTIVE: To perform an analysis
      of the hospital charges to determine the economic efficiency of each technique
      based on our experience at the Mt Sinai Medical Center, New York, NY. METHODS: A
      retrospective analysis of 16 patients diagnosed as having Zenker diverticulum was
      conducted. Eight randomly chosen patients underwent endoscopic stapling with an
      EndoGIA 35-mm endoscopic stapler (Ethicon Inc, Somerville, NJ), and 8 randomly
      chosen patients underwent a standard open approach with diverticulectomy. Medical
      records were reviewed to determine operative time, length of hospital stay, time
      to oral intake, and postoperative complications. A charge analysis of the
      operative and postoperative fees was also performed. Statistical analysis between
      the 2 groups was conducted using analysis of variance and the paired t test.
      RESULTS: The mean +/- SD operative time for the endoscopic stapling technique was
      25.5 +/- 15.78 minutes, which was significantly less (P<.001) than that for the
      open procedure, 87.6 +/- 35.10 minutes. The mean operative charges were roughly
      equivalent at US$ 5178 for the endoscopic procedure and US$ 5113 for the open
      procedure. The endoscopic procedure, while shorter in operative time, had the
      added expense of specialized equipment, specifically the EndoGIA endoscopic
      stapler. The mean +/- SD length of hospital stay for the endoscopic procedure was
      significantly shorter (P<.001) at 1.3 +/- 0.59 days vs 5.2 +/- 1.03 days for the
      open procedure. The inpatient hospital charges for the endoscopic group was also
      significantly less (P<.001) at a mean of US$ 3589 per stay vs US$ 11,439 for the
      open group. The mean +/- SD time to oral intake was significantly shorter (<.001)
      at a mean of US$ 3589 per stay vs US$ 11,439 for the open group. The mean +/- SD
      time to oral intake was significantly shorter (P<.001) in the endoscopic group at
      0.8 +/- 0.26 days vs 5.1 +/- 1.25 days for the open group. There were no major
      complications in either group, and all patients experienced resolution of
      preoperative symptoms. CONCLUSIONS: Compared with the standard open technique,
      the endoscopic stapling technique for the treatment of Zenker diverticulum
      results in a statistically significant shorter operative time, hospital stay, and
      time to resume oral feedings. While the charges of the operative procedures were
      roughly equivalent, the total hospital charges were significantly less for the
      patients treated endoscopically.

PMID- 11843722
TI  - Preincisional bupivacaine in posttonsillectomy pain relief: a randomized
      prospective study.
AB  - OBJECTIVE: To determine the effect of preincisional bupivacaine hydrochloride
      infiltration on postoperative pain after tonsillectomy. DESIGN: Prospective,
      randomized, double-blind clinical trial. SETTING: A secondary/tertiary referral
      center in Christchurch, New Zealand. PATIENTS: A volunteer sample of 70 patients,
      aged 16 to 42 years, with recurrent tonsillitis. Seven patients were excluded.
      INTERVENTIONS: After randomization, one group received 5 mL of 0.5% bupivacaine
      hydrochloride in the peritonsillar space, with the patient under general
      anesthesia. The other group received 5 mL of isotonic sodium chloride solution,
      with the patient under general anesthesia. Both groups underwent surgery with a
      standardized surgical and anesthetic technique. MAIN OUTCOME MEASURES:
      Postoperative pain was assessed with a visual analog scale at 15 minutes and 1,
      4, 12, 16, and 24 hours after the procedure. Postoperative analgesic requirement,
      length of admission, and antiemetic requirement were also assessed. RESULTS: No
      statistical difference was found between the 2 groups for postoperative pain by
      means of the visual analog scale at any time interval, nor was any statistical
      difference found for the other variables measured. A trend toward less pain in
      the immediate postoperative period in the group receiving bupivacaine was noted.
      CONCLUSION: No statistically significant benefit is found for use of
      preincisional bupivacaine in tonsillectomy.

PMID- 11843723
TI  - Otoacoustic emissions for monitoring aminoglycoside-induced ototoxicity in
      children with cystic fibrosis.
AB  - OBJECTIVE: To investigate whether transient-evoked and distortion-product (DP)
      otoacoustic emissions (OAEs) are more sensitive than pure-tone audiometry (PTA)
      in revealing gentamicin-induced ototoxicity in children with cystic fibrosis
      (CF). DESIGN: Prospective case-control study. SETTING: Tertiary referral
      audiologic center in conjunction with an academic pediatric CF unit.
      PARTICIPANTS: The study group consisted of a consecutive sample of 12
      audiologically normal children with CF and a history of gentamicin exposure (CF
      gentamicin group). The control groups consisted of 8 age-matched children with CF
      and 11 age-matched healthy volunteers. No member of the control groups had a
      history of aminoglycoside exposure. INTERVENTION: Members of the CF-gentamicin
      study group received 4 mg/kg of gentamicin per day for a mean of 14.2 days
      (range, 11-29 days). OUTCOME MEASURES: The PTA thresholds (250-8000 Hz) were the
      criterion standard. Transient-evoked OAEs' reproducibility at 5 frequency bands
      (800, 1600, 2400, 3200, and 4000 Hz) and total emission level were measured, as
      were DP-audiogram (DP-gram) amplitude (1001-6299 Hz), input-output function
      dynamic range, and detection thresholds at 4004, 6006, and 7996 Hz. Baseline
      measurements were compared between groups examining the effect of CF and previous
      gentamicin exposure (2-way analysis of variance). For the CF-gentamicin group,
      baseline measurements were compared with those at the end of the last gentamicin
      treatment (paired t test). RESULTS: The PTA findings were normal for all groups
      at baseline and remained normal in the CF-gentamicin group after treatment. The
      CF-gentamicin group had significantly lower transient-evoked OAEs total emission
      level, DP-gram amplitude at 5042 Hz, and input-output dynamic ranges with higher
      detection thresholds in all frequencies compared with both control groups, which
      was attributed completely to previous gentamicin exposure (P<.05). After
      treatment, further decreases in total emission levels, DP-gram amplitudes (>3000
      Hz), and dynamic ranges were noted, with increased detection thresholds (P<.05).
      CONCLUSIONS: Otoacoustic emissions measurement (especially of DP OAEs) proved
      more sensitive than PTA in revealing minor cochlear dysfunction after gentamicin
      exposure. They should be used for monitoring patients receiving ototoxic factors
      such as aminoglycosides.

PMID- 11843724
TI  - Computer-assisted voice analysis: establishing a pediatric database.
AB  - OBJECTIVES: To establish and characterize the first pediatric normative database
      for the Multi-Dimensional Voice Program, a computerized voice analysis system,
      and to compare the normative data with the vocal profiles of patients with vocal
      fold nodules. DESIGN: A cross-sectional, observational design was used to
      establish the normative database. The comparative study was completed using a
      case-control design. SETTING: University-based outpatient pediatric
      otolaryngology clinic. PARTICIPANTS: One hundred control subjects (50 boys and 50
      girls) aged 4 to 18 years contributed to the normative database. The voices of 26
      patients (19 boys and 7 girls) with bilateral vocal fold nodules were also
      analyzed. MAIN OUTCOME MEASURES: Demographic data, including sex, age, height,
      weight, body mass index, and cigarette smoke exposure, were obtained. The Multi
      Dimensional Voice Program extracted up to 33 acoustic variables from each voice
      analysis. RESULTS: The mean (SEM) values of each of the acoustic variables are
      presented. At age 12 years, boys experience a dramatic decrease in fundamental
      frequency measurements. The voices of patients with vocal fold nodules had
      significantly elevated frequency perturbation measurements compared with control
      subjects (P<.001). CONCLUSIONS: The vocal profile of children is uniform across
      all girls and prepubescent boys. Patients with vocal fold nodules demonstrated a
      consistent acoustic profile characterized by an elevation in frequency
      perturbation measurements. Normal acoustic reference ranges may be used to detect
      various vocal fold pathologic abnormalities and to monitor the effects of voice
      therapy.

PMID- 11843725
TI  - Midface reconstruction with the fibula free flap.
AB  - OBJECTIVE: To evaluate the use, indications, and outcomes of the fibula
      osteocutaneous free flap when reconstructing the midface. DESIGN: Retrospective
      review of a case series. SETTING: Tertiary referral center. PATIENTS: We
      evaluated all patients requiring midface reconstruction after tumor resection
      between January 1, 1994, and January 1, 2000. Twenty-seven individuals who lacked
      sufficient retentive surfaces and/or teeth to support a conventional prosthesis
      were offered vascularized bony reconstruction. INTERVENTIONS: All patients
      underwent fibular osteocutaneous free flap reconstruction of the midface: 16
      primarily, 11 secondarily. MAIN OUTCOME MEASURES: Success of free tissue
      transfer, perioperative complications, oral diet, speech, type of dental
      reconstruction, and cosmesis. RESULTS: Twenty-six of 27 flaps survived. Four
      patients had wound complications managed successfully with local wound care.
      Fourteen patients achieved a regular diet and 13 patients maintain a soft diet.
      Eighteen patients had osseointegrated implants placed, and 14 patients used an
      implant-borne prosthesis. Cosmetic results were judged to be excellent in 14
      patients; good in 8; fair in 4; and poor in 1. CONCLUSIONS: Use of the fibula
      osteocutaneous free flap to reconstruct the midface is highly reliable and our
      flap of choice for lower maxillary defects requiring bony reconstruction.
      However, when orbitozygomatic support is the primary objective, the utility of
      this flap is limited. Because of the complexity of this procedure, the choice of
      midface reconstruction technique should be individualized for each patient.

PMID- 11843727
TI  - Near-total laryngectomy for laryngeal carcinomas with subglottic extension.
AB  - OBJECTIVE: To investigate whether Pearson classic near-total laryngectomy is a
      sensible surgical treatment modality for laryngeal carcinomas with subglottic
      extension. DESIGN: Retrospective analysis of patients treated by near-total
      laryngectomy in a university hospital that is an academic tertiary health care
      center. PARTICIPANTS AND INTERVENTION: Medical and computer records of 135
      patients who were treated by near-total laryngectomy for laryngeal and
      hypopharyngeal carcinomas between April 1, 1989, and June 30, 2000, were searched
      thoroughly, and the final outcomes were confirmed by telephone contact. MAIN
      OUTCOME MEASURES: Survival rates of the patients with laryngeal carcinomas with
      subglottic extension treated by near-total laryngectomy were compared with those
      of the patients with malignancies of other laryngeal regions given the same
      treatment. RESULTS: Of the 135 patients in the study, 74 were available for
      determination of 5-year survival. The rate was 65.8% (27/41) for transglottic
      tumors, 53.8% (7/13) for supraglottic tumors, and 20.0% (4/20) for tumors with
      subglottic extension. Only 3 of 16 patients with laryngeal carcinomas with
      supraglottic or transglottic localization died of local recurrence; the rest of
      the deaths were from regional recurrence or distant metastasis. However, 6 of 13
      patients with subglottic extension died of local recurrence, 5 of peristomal
      recurrence, and only 2 of distant metastasis. CONCLUSIONS: Success was directly
      related to adherence to precise indications in cancer surgery. While near-total
      laryngectomy is an effective and reliable treatment modality in laryngeal cancer
      surgery, its effectiveness in laryngeal cancers with subglottic extension is
      debatable. These subglottic lesions should be treated by total laryngectomy,
      which is a more radical surgery.

PMID- 11843726
TI  - Analysis of cell-cycle checkpoint pathways in head and neck cancer cell lines:
      implications for therapeutic strategies.
AB  - OBJECTIVE: To determine the mechanism of action of paclitaxel (Taxol) and
      carboplatin in cell lines of head and neck squamous cell carcinoma (HNSCC).
      DESIGN: Four HNSCC cell lines were treated with paclitaxel and carboplatin, alone
      or in combination, and evaluated for cell-cycle position by means of flow
      cytometry, for molecular determinants of cell cycle by means of Western blotting
      and kinase analysis, and for anchorage-independent growth by means of soft-agar
      assays. RESULTS: Paclitaxel was more effective at inducing apoptosis and
      inhibiting anchorage-independent cell growth, compared with carboplatin. The
      activity of paclitaxel was correlated with an elevation of cyclin B1/CDC2
      activity, prolonged mitotic arrest, and Bcl-2 phosphorylation. In contrast,
      carboplatin arrested cells before mitosis. Combination treatment with both
      agents, simultaneously or sequentially, was more effective at inhibiting cell
      growth than either single agent. Cellular outcome was the same regardless of
      which drug was used first. The order of addition of these 2 drugs differentially
      affected cell-cycle position. Paclitaxel pretreatment arrested cells in mitosis,
      whereas carboplatin pretreatment or cotreatment resulted in premitotic arrest.
      CONCLUSIONS: To our knowledge, this study is the first to explore how paclitaxel
      and carboplatin, alone or in combination, differentially affect cell-cycle
      checkpoint response and HNSCC cell growth. These results provide molecular
      validation for the current clinical use of both drugs in combination and set the
      stage for analyses of patient tumor specimens.

PMID- 11843728
TI  - Swallowing outcomes following laryngectomy and pharyngolaryngectomy.
AB  - OBJECTIVES: To determine the incidence of dysphagia (defined as the inability to
      manage a diet of normal consistencies) at hospital discharge and beyond 1 year
      postsurgery and examine the impact of persistent dysphagia on levels of
      disability, handicap, and well-being in patients. DESIGN: Retrospective review
      and patient contact. SETTING: Adult acute care tertiary hospital. PATIENTS: The
      study group, consecutively sampled from January 1993 to December 1997, comprised
      55 patients who underwent total laryngectomy and 37 patients who underwent
      pharyngolaryngectomy with free jejunal reconstruction. Follow-up with 36 of 55
      laryngectomy and 14 of 37 pharyngolaryngectomy patients was conducted 1 to 6
      years postsurgery. MAIN OUTCOME MEASURES: Number of days until the resumption of
      oral intake; swallowing complications prior to and following discharge; types of
      diets managed at discharge and follow-up; and ratings of disability, handicap,
      and distress levels related to swallowing. RESULTS: Fifty four (98%) of the
      laryngectomy and 37 (100%) of the pharyngolaryngectomy patients experienced
      dysphagia at discharge. By approximately 3 years postsurgery, 21 (58%) of the
      laryngectomy and 7 (50%) of the pharyngolaryngectomy patients managed a normal
      diet. Pharyngolaryngectomy patients experienced increased duration of nasogastric
      feeding, time to resume oral intake, and incidence of early complications
      affecting swallowing. Patients experiencing long-term dysphagia identified
      significantly increased levels of disability, handicap, and distress. Patients
      without dysphagia also experienced slight levels of handicap and distress
      resulting from taste changes and increased durations required to complete meals
      of normal consistency. CONCLUSIONS: The true incidence of patients experiencing a
      compromise in swallowing following surgery has been underestimated. The
      significant impact of impaired swallowing on a patient's level of perceived
      disability, handicap, and distress highlights the importance of providing optimal
      management of this negative consequence of surgery to maximize the patient's
      quality of life.

PMID- 11843729
TI  - Computed tomography--guided wire localization: an intraoperative tool for head
      and neck resections.

PMID- 11843730
TI  - Management of a giant lymphatic malformation of the tongue.
AB  - Lymphatic malformations can occur anywhere in the head and neck, and when they do
      so in the oral cavity, they can present a potential hazard to the airway. We
      describe a 4-year-old girl with a giant lymphatic malformation of the tongue and
      neck. This report illustrates the particular difficulties that may be encountered
      in cases involving giant lymphatic malformations of the cervicofacial region in
      the pediatric population. An overview of the etiology, diagnosis, histology, and
      options for the management of such lesions is outlined.

PMID- 11843731
TI  - Pathology quiz case: sarcoidosis of the parotid glands.

PMID- 11843732
TI  - Radiology quiz case: postintubation subglottic and tracheal stenosis.

PMID- 11843733
TI  - Two for the price of one--is it worth it?

PMID- 11843734
TI  - Glycopyrronium and hypotension following combined spinal-epidural anaesthesia for
      elective Caesarean section in women with relative bradycardia.
AB  - The ability of glycopyrronium to reduce the severity of hypotension following
      subarachnoid block in parturients with a relative bradycardia was evaluated in a
      double-blind randomised controlled study. Women with a resting heart rate of < or
      = 80 beat x min(-1) presenting for elective Caesarean section were randomly
      allocated to receive either glycopyrronium 2 microg x kg(-1) or normal saline
      intravenously once positioned for combined spinal-epidural anaesthesia. Following
      spinal injection of 2.6 ml hyperbaric bupivacaine 0.5% and fentanyl 15 microg,
      women randomly allocated to the saline group were given 6 mg ephedrine so that
      all parturients received some prophylaxis against hypotension other than the
      fluid preload. Further ephedrine and fluid boluses were administered if mean
      arterial pressure fell 20% or more from resting values. Using a sequential
      analysis technique, analysis after the first 20 subjects indicated the study
      should be stopped, with no difference in ephedrine requirements or hypotension
      between the groups. We conclude that pretreatment with glycopyrronium 2 microg x
      kg(-1) is no more effective than 6 mg ephedrine in preventing hypotension
      following subarachnoid block in parturients with relatively low resting heart
      rates.

PMID- 11843736
TI  - Maternal cardiovascular consequences of positioning after spinal anaesthesia for
      Caesarean section: left 15 degree table tilt vs. left lateral.
AB  - Sixty healthy women undergoing elective Caesarean section were randomly allocated
      to either a measured 15 degrees left table tilt position (n = 31) or full left
      lateral position (n = 29) for a 15-min period after spinal blockade. Arm and leg
      blood pressure, ephedrine requirements, symptoms, fetal heart rate, cord gases
      and Apgar scores were recorded. Mean ephedrine requirements and incidence of
      hypotension were similar in the two groups. Arm systolic arterial pressure over
      time was similar in both groups, but leg systolic arterial pressure over time was
      significantly lower in the tilt group (p < 0.001); the mean leg systolic arterial
      pressure was lower for all 15 sequential recordings in the tilt group, reaching
      statistical significance (p < 0.05) at 4, 5, 6 and 8 min. Differences in maternal
      nausea, vomiting and bradycardia and fetal outcome were not statistically
      significant. Following spinal anaesthesia, even a true 15 degrees left table tilt
      position is associated with aortic compression.

PMID- 11843737
TI  - The impact of low-risk intensive care unit admissions on mortality probabilities
      by SAPS II, APACHE II and APACHE III.
AB  - A large proportion of intensive care unit patients are low-risk admissions.
      Mortality probabilities generated by predictive systems may not accurately
      reflect the mortality experienced by subpopulations of critically ill patients.
      We prospectively assessed the impact of low-risk admissions (mortality risk <
      10%) on the mortality estimates generated by three prognostic models. We studied
      1497 consecutive admissions to a general intensive care unit. The performance of
      the three models for subgroups and the whole population was analysed. The
      proportions of patients designated as low risk varied with the model and
      differences in model performance were most pronounced for these patients. The
      APACHE II mortality ratios (1.32 vs. 1.19) did not differ for low- and higher
      risk patients, but mortality ratios generated by APACHE III (2.38 vs. 1.23) and
      SAPS II (2.19 vs. 1.16) were nearly two-fold greater. Calibration for higher risk
      patients was similar for all three models but the APACHE III system calibrated
      worse than the other models for low-risk patients. This may have contributed to
      the poorer overall calibration of the APACHE III system (Hosmer-Lemeshow C-test:
      APACHE III chi(2) = 329; APACHE II chi(2) = 42; SAPS II chi(2) = 62). Imperfect
      characterisation of the large proportion of low-risk intensive care unit
      admissions may contribute to the deterioration of the models' predictive
      accuracies for the intensive care population as a whole.

PMID- 11843735
TI  - The effect of phenylephrine and norepinephrine in patients with chronic pulmonary
      hypertension*.
AB  - In this study the effect of phenylephrine and norepinephrine for the treatment of
      systemic hypotension were evaluated in patients with chronic pulmonary
      hypertension. When systemic hypotension (systolic arterial pressure < 100 mmHg)
      occurred following induction of anaesthesia, either phenylephrine or
      norepinephrine were infused in a random manner to raise the systolic blood
      pressure by 30% and 50% above baseline values. Norepinephrine decreased the ratio
      of pulmonary arterial pressure to systemic blood pressure without a change in
      cardiac index. However, phenylephrine did not increase arterial blood pressure by
      more than 30% from baseline in one-third of patients and decreased cardiac index
      without a significant decrease in ratio of pulmonary arterial pressure to
      systemic blood pressure. These vasoconstrictors showed different systemic and
      pulmonary haemodynamic effects in patients with chronic pulmonary hypertension as
      compared to acute pulmonary hypertension. Norepinephrine was considered to be
      preferable to phenylephrine for the treatment of hypotension in patients with
      chronic pulmonary hypertension.

PMID- 11843738
TI  - Effects of propofol and nitrous oxide on middle cerebral artery flow velocity and
      cerebral autoregulation.
AB  - We studied the effects of adding 50% nitrous oxide to propofol anaesthesia
      administered by target-controlled infusion on middle cerebral artery flow
      velocity and autoregulatory indices derived from transient hyperaemic response
      tests. Nine healthy (ASA 1) adult patients scheduled to undergo elective surgery
      were recruited. A standardised anaesthetic comprising alfentanil 10 microg x kg(
      1), propofol via a target-controlled infusion pump and vecuronium 0.1 mg x kg(-1)
      was used. Transcranial Doppler ultrasonography was used to measure middle
      cerebral artery (MCA) blood flow velocity and the transient hyperaemic response
      test was used to assess cerebral autoregulation. These measurements were
      performed while awake and then at an induction target concentration of propofol
      (the target at which consciousness was lost, mean 6.2 (SD 1.1) microg x ml(-1)).
      The measurements were repeated after the addition of 50% nitrous oxide to the
      breathing gas mixture. Propofol caused a significant decrease in MCA flow
      velocity and a significant increase in the strength of autoregulation. The
      addition of nitrous oxide had no significant effect on MCA flow velocity or
      cerebral autoregulation. These results suggest that addition of 50% nitrous oxide
      does not influence propofol-induced changes in cerebral haemodynamics.

PMID- 11843739
TI  - The ability of breathing system filters to prevent liquid contamination of
      breathing systems: a laboratory study.
AB  - The ability of 29 different breathing system filters (five pleated hydrophobic
      and 24 electrostatic) to prevent the passage of water was assessed. Five, 10 or
      20 ml of water was added on to the patient side of the filter during ventilation
      of a patient model with the filter layer orientated either horizontally or
      vertically. Water did not pass through the filter layer during any of the 30
      tests on the pleated hydrophobic filters. In contrast, water passed through the
      filter layer in 39 of the 144 tests on the electrostatic filters (27%; 95% CI for
      difference between the filter types 14-35%; p = 0.0004). For electrostatic
      filters, a smaller internal volume, a larger volume of water added, and having
      the filter layer horizontal rather than vertical all significantly increased the
      probability of water penetration. Although pleated hydrophobic filters would
      protect the breathing system against liquid contamination, electrostatic filters
      can also be used, provided the internal volume is chosen appropriately and the
      filter layer is vertical.

PMID- 11843740
TI  - Removal of obstructing blood clot from the lower airway: an alternative suction
      technique.
AB  - Clotted blood or organised thrombus in the lower airway may present clinicians
      with life-threatening airway obstruction or pulmonary collapse. An alternative
      suction technique is described, which applies suction directly to a tracheal
      tube.

PMID- 11843741
TI  - Does sevoflurane inhibit serum cholinesterase in children?
AB  - Serum cholinesterase activity was measured at induction, and following
      anaesthesia in 41 children aged between 4 and 30 months. The median exposure to
      sevoflurane was 273%.min. The results did not demonstrate any significant
      difference in cholinesterase activity, when expressed by gram of serum proteins
      following inhalation anaesthesia using sevoflurane or intravenous anaesthesia
      using propofol. The values (SD) obtained were 175 (42) UI.g(-1) before
      anaesthesia and 177 (43) UI.g(-1) following anaesthesia. The only change in
      cholinesterase activity detected was related to heamodilution. We conclude that
      plasma fluoride concentration following sevoflurane administration [13.8 (4.2)
      microm x l(-1)] is too low to exert an inhibiting effect on in vivo
      cholinesterase activity and that the previously reported decrease in mivacurium
      requirements during sevoflurane anaesthesia is unlikely to be due to inhibition
      by fluoride ions.

PMID- 11843742
TI  - A comparison of patient-controlled analgesia administered by the intravenous or
      intranasal route during the early postoperative period.
AB  - Intranasal administration of lipophilic opioids has been shown to be an effective
      method of administration which is devoid of major side-effects. Whether it is as
      effective as intravenous administration for patient-controlled analgesia (PCA)
      has been investigated for fentanyl and pethidine, but not for diamorphine. This
      study reports a randomised controlled trial designed to compare the effectiveness
      of diamorphine administered as PCA utilising either the intranasal or intravenous
      routes. We investigated 52 consecutive patients undergoing primary lower limb
      joint replacement surgery. Patients were randomly allocated to receive PCA
      diamorphine, administered either intravenously (0.5 mg bolus, 3 min lockout) or
      intranasally (1.0 mg bolus, 3 min lockout). Pain was assessed using a Visual
      Analogue Score (VAS) at rest and on movement on five occasions over the first 36
      h postoperatively. The results demonstrated that patients in the intranasal PCA
      group had significantly higher VAS scores than the intravenous group, both at
      rest (intranasal median 35.5 vs. intravenous median 20; p = 0.030) and on
      movement (intranasal median 64 vs. intravenous median 50; p = 0.016). However,
      significantly fewer patients in the intranasal group compared with the
      intravenous group suffered episodes of vomiting (intranasal 0/24 vs. intravenous
      6/24 patients; p = 0.022). We suggest that if a maximal reduction in pain score
      is considered the goal of PCA management, the intravenous route is preferable to
      the intranasal route.

PMID- 11843743
TI  - Sevoflurane vs. isoflurane: a clinical comparison in day surgery.
AB  - Discharge times after ambulatory surgery are determined by postoperative
      complications and in particular by the presence and severity of nausea and
      vomiting. Sevoflurane has become a popular agent for day-case surgery despite
      little evidence of clear advantages over current alternatives. We compared this
      agent with isoflurane in day-case patients undergoing knee arthroscopy in order
      to quantify the incidence of complications associated with each agent. One
      hundred and eighty patients received a standardised anaesthetic induction with
      propofol and fentanyl followed by maintenance with either isoflurane or
      sevoflurane. Standardised postoperative analgesic and anti-emetic drugs were
      prescribed. Any intra-operative cardiovascular or respiratory instability was
      recorded. After surgery, nausea, vomiting and pain were assessed. Almost all
      patients made an uneventful recovery and were discharged as scheduled. There was
      a significantly higher incidence of complications in the sevoflurane group. These
      included the presence of nausea and vomiting, and cardiovascular and respiratory
      complications. We found nothing to commend the routine use of sevoflurane rather
      than isoflurane in the context of day case anaesthesia.

PMID- 11843744
TI  - Disappearance of intraperitoneal gas following gynaecological laparoscopy.
AB  - We investigated 25 day case gynaecological laparoscopy patients to determine the
      duration of the pneumoperitoneum, the rate at which residual gas disappeared and
      the relative contribution of this gas to pain in the early postoperative period.
      The volume of gas was calculated from measurements of the subdiaphragmatic gas
      bubble obtained from an erect chest X-ray. Each patient was X-rayed twice, either
      immediately prior to discharge and at 24 h post laparoscopy, or at 24 h and 48 h
      post surgery. Patients were contacted by telephone at 24 and 48 h to confirm
      fitness to return for the X-ray and at the same time verbal pain and activity
      scores were recorded. We found that residual gas was almost entirely gone by 48 h
      following surgery and that it appeared to reduce in an exponential manner. The
      contribution of this gas to postoperative pain was significant in the first 24 h,
      but by 48 h it was considerably reduced. We conclude that in day case
      gynaecological laparoscopy patients, postoperative pneumoperitoneum is short
      lived, and that by 48 h its volume and contribution to postoperative pain should
      be minimal.

PMID- 11843745
TI  - Comparison of cyclizine and ondansetron for the prevention of postoperative
      nausea and vomiting in laparoscopic day-case gynaecological surgery.
AB  - Seventy-four patients undergoing laparoscopic gynaecological surgery were
      randomly allocated to two groups receiving cyclizine 50 mg or ondansetron 4 mg at
      induction of anaesthesia. Anaesthetic and postoperative analgesia regimens were
      standardised. Approximately half of the patients in each group experienced some
      degree of postoperative nausea and vomiting (cyclizine, 56%; ondansetron, 54%).
      There was no difference between groups in respect of pre- and postdischarge
      incidence. Mean (SD) time to eye opening was significantly prolonged in the
      cyclizine group [10 (4) min vs. 8 (2) min; p < 0.001], but this had no influence
      on discharge times. Cyclizine and ondansetron appear equally effective in
      preventing postoperative nausea and vomiting but the 10-fold price differential
      favours cyclizine.

PMID- 11843746
TI  - Supplementary oxygen administration for elective Caesarean section under spinal
      anaesthesia.
AB  - We investigated the necessity for administration of supplementary oxygen to
      mothers undergoing elective Caesarean section under spinal anaesthesia. Sixty
      nine women undergoing elective Caesarean section were randomly allocated to one
      of three groups to be given either oxygen (40%) by facemask, air by facemask or
      oxygen at 2 l x min(-1) by nasal cannulae. Umbilical arterial and venous blood
      samples were taken and analysed immediately after delivery. The results showed
      that there were no significant differences in the umbilical arterial or venous
      pH, partial pressure of oxygen and partial pressure of carbon dioxide between any
      of the three groups. We also assessed the patient acceptability of oxygen
      administered by facemask vs. nasal cannulae should the need for supplementary
      oxygen arise. It was found that use of the facemask impeded communication.

PMID- 11843747
TI  - Assessment of diaphragm function after stellate ganglion block using magnetic
      stimulation.
AB  - Stellate ganglion block is a procedure frequently used for the management of
      patients with chronic sympathetically mediated pain affecting the arm, neck or
      head. We studied the effect of stellate ganglion block on ipsilateral phrenic
      nerve function, and hence diaphragmatic strength, in 11 adult patients with
      chronic sympathetically mediated pain. Pre- and post-block forced vital capacity
      (FVC) measurements were recorded using a pneumotachograph and a Magstim nerve
      stimulator was used to generate pre- and post-block twitch mouth pressures
      (P(TWM)). This device can be used to stimulate the phrenic nerves and hence the
      diaphragm. The resulting change in airway pressure was measured at the mouth and
      has previously been shown to reflect diaphragm strength. There was no
      statistically significant difference in FVC or P(TWM) pre- or post stellate
      ganglion block. In conclusion, a stellate ganglion block has no adverse effect on
      ipsilateral phrenic nerve function or diaphragm strength in healthy adult
      patients.

PMID- 11843748
TI  - Supervision of trainee anaesthetists: a survey of opinions and practices.
AB  - This questionnaire survey investigated the different degrees of supervision of
      trainee anaesthetic senior house officers (SHOs) in hospitals across the United
      Kingdom, and compared it with past practices as well as with The Royal College of
      Anaesthetists' recommendations at that time. It is apparent that the duration of
      intensive supervision of new anaesthetic trainees has increased over the last 25
      years. This study assesses these changes in order to evaluate whether or not
      these reforms have achieved their intended outcomes.

PMID- 11843749
TI  - Nitrous oxide.

PMID- 11843750
TI  - Air ambulance transfers and patient deterioration.

PMID- 11843751
TI  - Blame it on the surgeons.

PMID- 11843752
TI  - Detachment of the tip of a gum-elastic bougie.

PMID- 11843753
TI  - Posterior tracheal wall perforation with the Blue Rhino tracheostomy set.

PMID- 11843754
TI  - Central lines and cerebral aneurysm surgery.

PMID- 11843755
TI  - Differences in the release of S100 protein during cardiopulmonary bypass.

PMID- 11843756
TI  - A highly mobile laryngeal tumour: inspiratory stridor and coughing attacks.

PMID- 11843757
TI  - Target-controlled infusions of propofol and remifentanil with closed-loop
      anaesthesia for hepatic resection.

PMID- 11843758
TI  - Anaesthesia for bronchoscopy.

PMID- 11843759
TI  - A critical incident: manufacturing or human error?

PMID- 11843760
TI  - From artificial hearts to financial markets.

PMID- 11843761
TI  - Low-flux versus high-flux synthetic dialysis membrane in acute renal failure:
      prospective randomized study.
AB  - The influence of dialyzer membrane on the morbidity and mortality of patients
      with acute renal failure remains a matter of debate. The aim of the prospective
      randomized clinical study was to assess the influence of the flux of a synthetic
      dialyzer membrane on patients' survival rate, restitution of renal function, and
      duration of hemodialysis treatment of patients with acute renal failure as a part
      of multiorgan failure. Seventy-two patients treated in intensive care units of
      the University Medical Center Ljubljana were randomized according to the dialyzer
      used throughout the duration of hemodialysis treatment. There were 38 patients in
      the low-flux group (dialyzer F6, low-flux polysuphone, Fresenius, Bad Homburg,
      Germany) and 34 patients in the high-flux group (dialyzer Filtral 12, sulphonated
      high-flux polyacrylonitrile, Hospal, Industrie Meyzieu, France). Both groups were
      balanced in terms of sex, age, APACHE II score, oliguria before dialysis, cause
      of acute renal failure, inotropic support, mechanical ventilation, and the number
      of failing organs. The patients' survival rate was 18.7% in the low-flux group
      and 20.6% in the high-flux group. Ten patients (26.3%) recovered their renal
      function in the low-flux group and 8 (23.5%) in the high-flux group. Hemodialysis
      treatment lasted 11.2 days in the low-flux and 10.7 days in the high-flux group.
      An analysis of subgroups with a lower mortality rate (subgroup of patients
      without oliguria and subgroup of patients with less than 4 failed organ systems)
      did not show significant differences between the low-flux and high-flux groups in
      terms of survival rate, recovery of renal function, and duration of hemodialysis
      treatment. In conclusion, no significant differences were found in the results of
      low-flux versus high-flux synthetic membrane dialyzer treatment in patients with
      acute renal failure as a part of multiorgan failure in terms of survival rate,
      recovery of renal function, incidence of oliguria during hemodialysis, and
      duration of hemodialysis treatment. The number of failing organs seems to be the
      most important single factor determining the survival of patients with acute
      renal failure as a part of multiorgan failure.

PMID- 11843762
TI  - Pyrogen retention by highly permeable synthetic membranes during in vitro
      dialysis.
AB  - Pyrogen permeability of the new highly permeable synthetic membrane
      polyethersulfone (DIAPES) was compared to polysulfone in vitro dialysis
      experiments with heparinized human donor blood in the blood compartment. After
      sterile dialysis for 5 min, dialysate was contaminated with a culture filtrate of
      Pseudomonas aeruginosa using high and moderate challenge doses (Limulus assay
      reactivity 20,000 EU/ml and 50 EU/ml, respectively). Whole blood samples were
      separated from the blood compartment during the sterile (5 min) and contaminated
      (60 min) phases of dialysis and incubated for 6 h at 37 degrees C. Blood samples
      were lysed, and interleukin-1beta and tumor necrosis factor alpha were measured
      by specific ELISAs. Moderate dialysate contamination (50 EU/ml) did not induce
      detectable cytokine production in whole blood. High challenge dose (20,000 EU/ml)
      induced whole blood interleukin-1beta and tumor necrosis factor alpha production
      in the blood compartment, which was higher with DIAPES than with polysulfone
      after 30 min. After 60 min, membrane-dependent differences were no longer
      detectable. Pyrogen concentrations in the dialysate decreased with time
      indicating adsorption of cytokine-inducing substances to the dialyzer membrane.
      Pyrogens adsorbed to dialyzer membranes were resuspended during recirculation of
      sterile phosphate-buffered saline in the dialysate compartment and retained
      cytokine-inducing activity as seen from whole blood incubation experiments.
      DIAPES and polysulfone adsorbed pyrogens in the presence of whole blood. Pyrogen
      adsorption to the membrane polymer and/or to the protein coat on the membrane
      prevented the passage of pyrogens in the presence of moderately contaminated
      dialysate. High grade dialysate contamination caused breakthrough of pyrogens
      into the blood with DIAPES and polysulfone. In order to reduce the risk of a
      dialysis-dependent inflammatory response, dialysate of high bacteriological
      quality (ultrapure dialysate) should be mandatory.

PMID- 11843763
TI  - Effects of ultrafiltration, dialysis, and temperature on gas exchange during
      hemodiafiltration: a laboratory experiment.
AB  - To study gas exchange in the filter during continuous venovenous
      hemodiafiltration (CVVHDF), an air-tight heated mixing chamber with adjustable
      CO2 supply was constructed and connected to a CVVHDF monitor. Bicarbonate-free
      crystalloid (Part 1) and packed red blood cell (Part 2) solutions were circulated
      at 150 ml x min(-1). Gas exchange expressed as pre-postfilter difference in CO2
      and O2 contents was measured at different CVVHDF settings and temperatures of
      circulating and dialysis solutions. Ultrafiltration was most efficacious for CO2
      removal (at 1,000 ml x h(-1) ultrafiltration CO2 losses reached 13% of prefilter
      CO2 content). Addition of dialysis (1,000 ml x h(-1)) increased CO2 loss to 17%
      and at maximal parameters (filtration 3,000 ml x h(-1), dialysis 2,500 ml x h(
      1)), the loss of CO2 amounted to 35% of prefilter content. Temperature changes of
      circulating and/or dialysis fluids had no significant impact on CO2 losses. The
      O2 exchange during CVVHDF was negligible. Currently used CVVHDF is only
      marginally effective in CO2 removal. Higher volume ultrafiltration combined with
      dialysis can be expected to reach clinical significance.

PMID- 11843764
TI  - Immunoglobulin treatment versus plasma exchange in patients with chronic moderate
      to severe myasthenia gravis.
AB  - The purpose of this study was to compare the efficacy of high-dose intravenous
      immunoglobulin (IVIG) treatment with plasma exchange in patients suffering from
      moderate to severe myasthenia gravis (MG) in a stable phase. There are no
      controlled studies comparing IVIG with plasma exchange in patients who despite
      immunosuppressive treatment have persistent incapacitating MG symptoms. This was
      a controlled crossover study. Twelve patients with generalized moderate to severe
      MG on immunosuppressive treatment for at least 12 months were included. The
      patients were evaluated clinically using a quantified MG clinical score (QMGS)
      before and at follow-up visits after each treatment. One week after the
      treatments, the patients who received plasma exchange treatment showed a
      significant improvement in QMGS compared to baseline but although some
      improvement was seen after IVIG this did not reach statistical significance. Four
      weeks after both plasma exchange and IVIG treatments, there was a significant
      improvement in QMGS compared to baseline. One week and 4 weeks after treatment,
      no significant difference between the 2 treatments was found. Both treatments
      have a clinically significant effect 4 weeks out in patients with chronic MG, but
      the improvement has a more rapid onset after plasma exchange than after IVIG.

PMID- 11843765
TI  - A hybrid compliant vascular graft seeded with microvascular endothelial cells
      extracted from human omentum.
AB  - We report the development of a hybrid vascular graft using an innovative
      compliant poly(carbonate-urea)urethane unlike any previous polyurethane MyoLink
      as a permanent scaffold. The engineered graft has a hierarchical arterial
      structure: a monolayer of oriented microvascular endothelial cells (MVECs) and 3
      D matrix (human collagen Type 4/dermatan sulfate) bonded onto MyoLink. The
      grafts' clinical feasibility was evaluated by determining optimal MVEC seeding
      density, incubation time, viability, and adhesion of these cells when exposed to
      arterial shear stress. MVECs from human omentum were isolated by a new
      centrifugation protocol, radiolabeled and seeded onto hybrid graft 2 to 18 x 105
      cells/cm(2) for 24 h at 37 degrees C and for 1 to 5 h at 6 x 105 cells/cm(2),
      washed 3 times, and gamma counted. Qualitative assessment of seeding
      density/incubation was also undertaken with scanning electron microscopy (SEM)
      and viability tested with a modified Alamar Blue assay. A pulsatile flow phantom
      was used to subject the hybrid graft (200 mm length, 5 mm internal diameter)
      seeded with radiolabeled MVECs (6 x 105 cells/cm(2) at 2 h) to arterial shear and
      dynamic scintigraphy images acquired in real time using a nuclear medicine gamma
      camera system during 14 h of perfusion (n = 6). The optimal seeding density was 6
      x 105 cells/cm(2), and qualitative SEM confirmed this. Incubating cells for 2 h
      produced significantly greater cell attachment than was seen for 1 h incubation
      (p < 0.05), and there was no significant difference in adhesion between cells
      incubated over the 2 h. Exposure of grafts to acute shear stress resulted in
      significantly higher proportions of initial cells attached to hybrid grafts
      compared to native MyoLink grafts (67 +/- 3% versus 55 +/- 2%, p < 0.001). As
      shown here, tissue engineering of native Myolink grafts significantly reduces the
      seeding density and incubation time to produce a monolayer onto which cells
      adhere to better.

PMID- 11843766
TI  - Refractive tunnel keratoplasty with synthetic implants modified by a gas
      discharge plasma.
AB  - Various methods of refractive interlamellar tunnel keratoplasty with synthetic
      implants modified by low-temperature gas-discharge plasma were used for
      correction of myopia and myopic astigmatism. Experiments carried out with
      laboratory rabbits revealed that pretreatment of hydrogel, silicon, and
      polymethylmethacrylate by gas-discharge plasma enhances the tolerance of corneal
      stroma to these synthetic materials. Clinical studies with hydrogel have shown
      that gas-discharge plasma treatment of traditional polymer materials is a
      promising method for achieving improved biocompatibility of synthetic materials
      to corneal stroma. Forty-four clinical tunnel keratoplasties have been conducted
      on humans with gas-discharge-plasma-treated hydrogel. The patients had a high
      degree of myopia (from 7.0 to 28.0 D) and myopic astigmatism (within the range of
      5.0 to 11.0 D). Surgical methods were similar to those developed during the
      experimental stage of work. The patients were followed postoperatively for up to
      8 years. According to these observations, circular tunnel keratoplasty with
      synthetic implants reduced spherical myopia up to 20.0 D. Methods for correcting
      of both simple and complex myopic types of astigmatism have been developed. Arc
      type sectoral tunnel keratoplasty and elliptical tunnel keratoplasty allowed
      correction of myopic astigmatism up to 11.0 D.

PMID- 11843767
TI  - Neonatal and pediatric extracorporeal membrane oxygenation using nonocclusive
      blood pumps: the Vienna experience.
AB  - Neonatal and pediatric extracorporeal membrane oxygenation (ECMO) is carried out
      commonly using occlusive blood pumps. Centrifugal pumps provide simple and safe
      technology for transportation on ECMO. The assistence respiratoire extra
      corporelle (AREC) system enables single needle venovenous ECMO for infants. We
      report on our experience with neonatal and pediatric ECMO treatments using
      nonocclusive blood pumps. One-hundred forty-six ECMO treatments were performed
      for cardiac, neonatal, and pediatric indications in 54, 19, and 27% of cases.
      Centrifugal pumps were used in 99, and the AREC system in 42 cases. Hospital
      mortality was estimated retrospectively and influence of type of pump, type of
      ECMO belonging to indication group, and lactate at ECMO installation were
      estimated. Irreversible organ failure leading to ECMO termination was
      investigated within groups of indications. Survival (recent 50 ECMO treatments)
      was 80, 70, 43, and 30% after meconium aspiration syndrome, acute respiratory
      distress syndrome, cardiac surgery, and prolonged resuscitation. Lactate
      exceeding 100 mg/dl at ECMO installation predicted significantly worse outcome.
      Cerebral damage was the main reason for ECMO termination in all but persistent
      circulatory failure in the cardiac group. Myocardial recovery resulted in all
      except 2 cardiac cases. Nonocclusive blood pumps can be used safely in neonatal
      and pediatric ECMO. Early installation may improve outcome markedly. In cardiac
      cases results of surgery should be thoroughly investigated on the table before
      ECMO installation to prevent hopeless ECMO treatments.

PMID- 11843768
TI  - Percutaneous extracorporeal life support for treatment of fatal mechanical
      complications associated with acute myocardial infarction.
AB  - Mechanical complications of acute myocardial infarction (AMI), such as free wall
      rupture, ventricular septal perforation (VSP), and mitral regurgitation due to
      papillary muscle rupture, are associated with high mortality rates. These
      complications result in extreme deterioration and increased risk of death in
      patients who do not receive timely resuscitation and surgical treatment. We
      studied the effectiveness of percutaneous extracorporeal life support (ECLS) for
      fatal mechanical AMI complications. Nine patients (7 men and 2 women, mean age 69
      +/- 6 years) who suffered circulatory collapse refractory to conventional
      resuscitation were treated with ECLS. Circulatory collapse was caused by free
      wall rupture in 4 patients, VSP in 4, and mitral regurgitation due to papillary
      muscle rupture in 1. All patients were successfully resuscitated by ECLS and
      underwent surgical repair with conventional cardiopulmonary bypass. Eight
      patients required ECLS after surgery. Four of the 9 patients (2 with free wall
      rupture, 1 with VSP, and 1 with papillary muscle rupture) were successfully
      weaned from ECLS and were discharged. Three of the 4 survivors had no major
      complications, but the remaining survivor suffered neurological deficit. Four
      patients died while on devices. The duration of ECLS was from 13 to 167 h (mean
      76 +/- 57 h) with a maximum bypass flow of 2.0 to 3.9 L/min (mean 2.9 +/- 0.6
      L/min). There were no device-related complications during the support period.
      Total weaning rate was 56% (5/9), and survival was 44% (4/9). We conclude that
      ECLS can provide appropriate circulatory support during resuscitation and
      subsequent postoperative circulatory support for cardiovascular collapse
      associated with AMI complications.

PMID- 11843769
TI  - Antiinflammatory effect of heparin-coated circuits with leukocyte-depleting
      filters in coronary bypass surgery.
AB  - Cardiac surgery with cardiopulmonary bypass is associated with a systemic
      inflammatory response. We examined combined use of heparin coating of the
      cardiopulmonary bypass circuit and a leukocyte-depleting arterial line filter to
      reduce this response. Thirty patients were allocated randomly to equal groups
      with a conventional circuit and arterial line filter (C group), a heparin-coated
      circuit with a conventional filter (H group), or a heparin-coated circuit with a
      leukocyte-depleting arterial line filter (HF group). Cytokines and respiratory
      function were repeatedly measured perioperatively. Plasma interleukin (IL)-6
      concentrations in the HF group were lower than in the C group immediately
      following bypass and operation, at 4 h, and 12 h (p < 0.05). Plasma IL-8 was
      lower in the HF group than in the C group at 4 h (p < 0.05). The respiratory
      index was lower immediately after bypass in the HF group than the C group (0.61
      +/- 0.2 versus 1.05 +/- 0.4, p < 0.05). Heparin-coated circuits with leukocyte
      depleting filters decrease inflammatory responses and improve pulmonary function
      during operation.

PMID- 11843770
TI  - The bradykinin response and early hypotension at the introduction of continuous
      renal replacement therapy in the intensive care unit.
AB  - We assessed the relationship of certain clinical variables (including bradykinin
      [BK] release and dialysis membrane) to initial mean arterial pressure (MAP)
      reduction in 47 patients requiring continuous renal replacement therapy (CRRT) in
      an intensive care unit. The pretreatment MAP was 84 +/- 14 mm Hg for the group as
      a whole. The initial MAP reduction was 11.5 (7-20) mm Hg, occurring 4 to 8 min
      after connection. MAP reduction was 9 (6-15) mm Hg with polyacryonitrile (PAN)
      membranes versus 14 (5-19) mm Hg with polysulfone (PS) (not significant). There
      were positive correlations between MAP reduction and BK concentration at 3 (BK3;
      r = 0.58, p < 0.01) and 6 (BK6; r = 0.67, p < 0.001) min with PAN but not with
      PS. A greater reduction in MAP was seen in patients who were not receiving
      inotropic support (Mann-Whitney test, p < 0.01). BK3 and BK6 values for the PAN
      and PS groups were not significantly different. However, BK concentrations
      greater than 1,000 pg/ml were only seen with PAN (6 patients, MAP reduction 27
      [17-31] mm Hg). There were positive (albumin) and negative (age; acute
      physiology, age, and chronic health evaluation score; C-reactive protein [CRP];
      calcium) correlations with BK3/BK6 in the PAN and PS groups, some of which
      (albumin, CRP) reached statistical significance. In summary, MAP reduction at the
      start of CRRT correlates with BK concentration. The similarity of response with
      PAN and PS suggests an importance for other clinical factors. In this study,
      hemodynamic instability was more likely in patients with evidence of a less
      severe inflammatory or septic illness.

PMID- 11843771
TI  - Errors involved in the application of an imperfect peritoneal volume marker.
AB  - Peritoneal volume markers have been used in numerous studies on fluid transport
      in peritoneal dialysis. The basic assumption used was that the macromolecular
      marker was stable and that the free fraction of a label (usually radiolabel) was
      negligibly small. In this study are presented theoretical investigations on the
      errors involved in application of an imperfect volume marker containing free
      fraction of a label. These investigations were used in assessing the errors in
      calculation of peritoneal volume time course, V, and fluid absorption rate
      (estimated by volume marker clearance, kE) using data from 20 clinical dwell
      studies with 1.36% Dianeal dialysis solution and radioiodinated human serum
      albumin as a volume marker. It has been shown that with an in vitro measured 125I
      free fraction of 2.72%, the error of kE estimation was 11%. However, the maximal
      error in estimation of V was only 0.2%. In conclusion, the performed analysis
      implies that calculation of the peritoneal volume time course during the dwell
      (with correction for the volume marker elimination) is very reliable, and the
      existence of a free fraction of a volume marker label results in a negligibly
      small error. However, even small free fraction of the label results in a
      significant overestimation of the fluid absorption rate.

PMID- 11843772
TI  - Hemodynamic exercise response in calves with an implantable biventricular
      centrifugal blood pump.
AB  - An implantable biventricular assist device (BVAD) has been developed at Baylor
      College of Medicine using 2 centrifugal blood pumps. The aim of this study was to
      investigate the exercise-reflex response during nonpulsatile biventricular
      assistance and to evaluate to which degree the autoregulation of the system would
      accommodate the changed hemodynamic situation during physical exercise. The
      Baylor Gyro PI 710 BVAD has been implanted into 2 calves (strain half-Dexter) in
      a biventricular bypass fashion with native heart remaining. Allowing a 10 day
      convalescence, 2 animals were subjected to incremental exercise tests. The speed
      of the treadmill was increased at zero slope from 0.7 mph to 1.5 mph with
      increments of 0.2 mph every 3 min. During the exercise the pump flows were
      maintained at a fixed rate (6.93 +/- 0.01 L/min for the left ventricular assist
      device and 5.36 +/- 1.44 L/min for the right ventricular assist device).
      Hemodynamic parameters and pump performance were recorded continuously. The
      cardiac output (CO) and heart rate (HR) increased significantly during the
      exercise. CO increased from 11.1 +/- 0.3 to 13.1 +/- 0.4 L/min, and HR increased
      from 99 +/- 7.1 to 114 +/- 2.8 bpm, respectively. Mean aortic pressure, central
      venous pressure, and left arterial pressure did not change significantly. Also,
      no change was observed for the left and right pump flows. This totally
      implantable BVAD showed excellent long-term performance without any mechanical
      problems. It is feasible to operate without impairment under physical activity.
      However, the natural heart dominated the hemodynamic response during exercise
      under BVAD support. The left and the right pump flows did not increase
      spontaneously with exercise. We therefore conclude that a servo CO control system
      is necessary to regulate pump flows even during moderate exercise.

PMID- 11843773
TI  - Change in vasoconstrictive function during left heart bypass.

PMID- 11843776
TI  - Introduction: Special issue on the genetics of bipolar disorder.

PMID- 11843777
TI  - Psychiatric diagnoses in the context of genetic studies of bipolar disorder.
AB  - Precise definition of the phenotype is an issue of critical importance for the
      future success of genetic studies of bipolar disorders. So far, an uncertain
      phenotypic spectrum and genetic heterogeneity are realities that have hampered
      progress in genetic studies. While recognition of a broader spectrum of related
      illnesses is important for some applications, for genetic studies a narrow
      spectrum of illness closely tied to the genotype is paramount. This paper
      highlights current dilemmas and trends associated with phenotype specification
      and traces historical approaches. Finally, we explore a number of strategic
      directions in the diagnostic approach to bipolar disorders that may better serve
      genetic studies.

PMID- 11843778
TI  - Molecular linkage studies of bipolar disorders.
AB  - OBJECTIVES: To review the reports of linkage findings for bipolar disorder.
      METHODS: Literature review of published linkage findings in bipolar disorder.
      RESULTS: There are several regions of the human genome that have been implicated
      repeatedly by independent investigators. These include 4p16, 12q24, 18q22, 18p11,
      21q21 and 22q11. Two of these regions (18p11 and 22q11) are also implicated in
      genome scans of schizophrenia, suggesting that these two distinct nosological
      categories may share some genetic susceptibility. This hypothesis can only be
      tested when the underlying genes are identified.

PMID- 11843779
TI  - Association studies of bipolar disorder.
AB  - Association studies in outbred populations represent an important paradigm for
      investigation of complex traits, such as bipolar disorder, both to follow-up
      regions of interest from linkage studies (by systematic linkage disequilibrium
      mapping and positional candidate studies) and for pure functional studies. The
      advantages of the association method include its relative robustness to genetic
      heterogeneity and the ability to detect much smaller effect sizes than are
      detectable using feasible sample sizes in linkage studies. The candidate gene
      approach is potentially very powerful, particularly when used within the context
      of a VAPSE (variation affecting protein structure or expression) paradigm, but a
      major problem is that the efficiency in the choice of candidates is inevitably a
      function of the level of previous understanding of disease pathophysiology. To
      date, most candidate gene studies in bipolar disorder have focussed on the major
      neurotransmitter systems that are influenced by medication used in clinical
      management of the disorder. Early studies often used anonymous markers in the
      hope of detecting linkage disequilibrium but recently direct examination of
      polymorphisms of known or presumed functional relevance has become more usual.
      Most studies in the literature have been of the unrelated case-control design
      with samples rarely exceeding 200-300 subjects. No definitive findings have yet
      emerged although there have been some interesting preliminary findings including
      those with polymorphisms within the genes encoding catechol-o-methyl transferase
      (COMT), monoamine oxidase A (MAOA) and the serotonin transporter (hSERT; 5-HTT).
      In this article we critically review the current status of the literature within
      the context of the important methodological issues and limitations inherent in
      the use of association studies for genetic dissection of bipolar disorder. We
      conclude by examining likely future directions and developments in the field.

PMID- 11843780
TI  - Population isolates: their special value for locating genes for bipolar disorder.
AB  - OBJECTIVES: Population isolates offer several advantages for those hoping to
      identify predisposition genes for bipolar disorder (BP). In this review article,
      the rationale for performing gene mapping studies in this type of population and
      the results of genetic mapping studies performed to date in population isolates
      are presented. METHODS: This article begins with a brief review of the concepts
      involved in mapping genes for BP. The concept of populations that show some
      degree of historical isolation and their special utility for certain types of
      gene mapping is presented. Methods of statistical analysis particularly relevant
      for gene mapping of complex diseases like BP are presented. Finally, several BP
      gene studies conducted to date in several population isolates are reviewed.
      RESULTS: Genetic mapping studies of BP have occurred thus far in several isolates
      or sub-isolates, including the Amish population, Costa Ricans, Finnish, and
      Canadians (in Quebec), and significant linkage scores have been identified in the
      latter three isolates. CONCLUSIONS: Possible greater homogeneity and greater
      consistency of diagnosis are factors that have been cited in several studies of
      BP done in isolates to date. Another special advantage of working in certain
      types of population isolate is their appropriateness for using certain types of
      association or linkage disequilibrium-based approaches at both the genome
      screening and fine mapping stages. These tests include mapping by linkage
      disequilibrium analyses, an approach that allows mapping to occur at the
      population, rather than the pedigree, level.

PMID- 11843781
TI  - Genetic factors and treatment of mood disorders.
AB  - OBJECTIVES: This paper reviews the pharmacogenetics of mood disorders. METHODS:
      We have searched the literature for published studies and abstracts relevant for
      genetic effects in acute antidepressant treatment and in long-term prophylactic
      treatment. RESULTS: The most promising findings to date show an association of
      the serotonin transporter (5-HTT) gene and the response to serotonin reuptake
      inhibitors. Genetic factors also appear to play a significant role in the outcome
      of long-term lithium treatment. The phenotype of lithium-responsive bipolar
      disorder is associated with stronger genetic effects as well as with an increased
      phenotypic homogeneity. CONCLUSIONS: Genetic factors likely influence treatment
      response in mood disorders. Clarifying their precise role will have implications
      for treatment as well as for understanding the pathophysiological mechanisms of
      these disorders.

PMID- 11843782
TI  - Review of studies of child and adolescent offspring of bipolar parents.
AB  - OBJECTIVE: The authors reviewed studies of child and adolescent offspring of
      bipolar (BP) parents. Findings from these studies are critically discussed with
      respect to methodological issues that can inform future designs. METHODS: A
      Medline search was performed to identify studies that examined child and
      adolescent offspring of BP parents. Publications were excluded if they did not
      separate offspring of BP parents from offspring of major depressive disorder or
      schizoaffective parents ("affective offspring") or did not separately analyze
      data from child- and adolescent-age versus adult offspring. RESULTS: Seventeen
      studies fit these review criteria. Rates of mood disorders in child and
      adolescent offspring of BP parents ranged from 5 to 67% compared with rates in
      offspring of healthy volunteers of 0-38%. Rates of non-mood disordered
      psychopathology ranged from 5 to 52% in offspring of BP parents and from 0 to 25%
      in offspring of healthy volunteers. Rates of mood disorders and of other
      psychopathology were increased in offspring of BP parents compared with offspring
      of healthy volunteers in all of the eight studies that included a comparison
      group of offspring of healthy volunteers. CONCLUSIONS: Studies suggest that
      children (< or =21 years) of BP parents are at increased risk for developing mood
      and other disorders (e.g., disruptive, anxiety). Therefore, additional
      investigations are clearly warranted. In the context of current research on
      diagnosis, assessment, longitudinal course and comorbidity of childhood mania,
      the following suggestions for the design of future studies should be considered:
      1) Phenotypic specification of bipolar manifestations (e.g., BP-I, BP-II, BP-NOS)
      in child/adolescent offspring and in bipolar parents themselves. 2) Control
      groups that are pediatric-age relevant and thus include attention-deficit
      hyperactivity disorder. 3) Assessments that include items for prepubertal mania
      and for onsets and offsets of all occurrences of symptoms and of environmental
      factors (e.g., life events) in offspring and in parents so that trajectories of
      overlap and sequence between child and parental mania can be investigated. 4)
      These detailed onsets and offsets of symptoms are also necessary to investigate
      prodromal manifestations of mania in the offspring. 5) Unaffected offspring
      present a unique opportunity to study pre- and postmorbid cognitive and
      physiological endophenotypes and structural and functional brain abnormalities.
      Findings from offspring studies will be crucial to inform research on the
      development of early intervention and prevention strategies.

PMID- 11843783
TI  - Suicidal behavior: is there a genetic predisposition?
AB  - OBJECTIVES: To review the data that support the role of genetic factors in the
      predisposition to suicidal behavior and to examine whether or not these factors
      are part of the genetic liability to mood disorders. To review molecular genetic
      studies carried out in suicidal behavior. METHODS: A review of the literature was
      carried out by means of systematic bibliographic database searches and
      complemented by searches in the references of relevant publications. RESULTS:
      There is consistent evidence suggesting that genetic factors play an important
      role in the predisposition to suicide and suicidal behaviors. Although there is
      important overlap between suicide and mood disorders, a common genetic liability
      seems unlikely. It is possible that part of the predisposition to suicide may be
      transmitted via the presence of impulsive and impulsive-aggressive behaviors. An
      increasing number of molecular genetic studies have been carried out in subjects
      with suicidal behavior. There is some support for a role of some genes that code
      for components of the serotonergic pathway in the etiology of suicidal behavior,
      but these studies are still preliminary. CONCLUSIONS: Further studies are needed
      at the epidemiological, clinical and molecular level to better characterize the
      genetics of suicide. These should control for the presence of behaviors that are
      considered as part of the phenotypic spectrum of suicide.

PMID- 11843784
TI  - Acupuncture to treat nausea and vomiting in early pregnancy: a randomized
      controlled trial.
AB  - BACKGROUND: Nausea and vomiting in early pregnancy are troublesome symptoms for
      some women. We undertook a single blind randomized controlled trial to determine
      whether acupuncture reduced nausea, dry retching, and vomiting, and improved the
      health status of women in pregnancy. METHODS: The trial was undertaken at a
      maternity teaching hospital in Adelaide, Australia, where 593 women less than 14
      weeks' pregnant with symptoms of nausea or vomiting were randomized into 4
      groups: traditional acupuncture, pericardium 6 (p6) acupuncture, sham
      acupuncture, or no acupuncture (control). Treatment was administered weekly for 4
      weeks. The primary outcomes were nausea, dry retching, vomiting, and health
      status. Comparisons were made between groups over 4 consecutive weeks. RESULTS:
      Women receiving traditional acupuncture reported less nausea (p < 0.01)
      throughout the trial and less dry retching (p < 0.01) from the second week
      compared with women in the no acupuncture control group. Women who received p6
      acupuncture (p < 0.05) reported less nausea from the second week of the trial,
      and less dry retching (p < 0.001) from the third week compared with women in the
      no acupuncture control group. Women in the sham acupuncture group (p < 0.01)
      reported less nausea and dry retching (p < 0.001) from the third week compared
      with women in the no acupuncture group. No differences in vomiting were found
      among the groups at any time. CONCLUSION: Acupuncture is an effective treatment
      for women who experience nausea and dry retching in early pregnancy. A time
      related placebo effect was found for some women.

PMID- 11843785
TI  - Prepartum work, job characteristics, and risk of cesarean delivery.
AB  - BACKGROUND: Reducing the rate of cesarean deliveries in the United States is a
      high priority among public health officials and members of the medical community.
      Many factors known to contribute to an individual woman's risk of having a
      cesarean rather than a vaginal delivery are not readily altered by public policy
      intervention. In this study we explored the effects on type of delivery of
      prepartum work practices, a category of factors that has a potential to affect
      the likelihood of cesarean delivery and to be amenable to change. METHODS: Data
      are from U.S. Food and Drug Administration's Infant Feeding Practices Study,
      using questions on mail surveys administered prenatally and at 1 month
      postpartum. The sample comprised 1194 women who worked during pregnancy. The
      outcome measure is type of delivery. Predictor variables are characteristics of
      prepartum work: how far into their pregnancy the women work, number of hours
      worked, and occupation. RESULTS: For most women, maintaining employment through
      the third trimester, working long hours, and working in certain occupations are
      not independently associated with the odds of having a cesarean delivery.
      However, we found marginally significant evidence that those women who worked
      more than 40 hours a week in a sales job were more likely to have cesarean
      deliveries than women who worked in other occupations. Conversely, women working
      part-time in sales jobs were less likely to have a cesarean delivery. CONCLUSION:
      This study provides evidence that prenatal work does not substantially increase
      the probability of having a cesarean delivery in most occupational categories.

PMID- 11843786
TI  - Birth position, accoucheur, and perineal outcomes: informing women about choices
      for vaginal birth.
AB  - BACKGROUND: The literature is tentative in establishing links between birth
      position and perineal outcome. Evidence is inconclusive about risks and benefits
      of women's options for birth position. The objective of this study was to gain
      further evidence to inform perinatal caregivers about the effect of birth
      position on perineal outcome, and to assist birth attendants in providing women
      with information and opportunities for minimizing perineal trauma. METHODS: Data
      from 2891 normal vaginal births were analyzed. Descriptive statistics were
      obtained for variables of interest, and cross-tabulations were generated to
      explore possible relationships between perineal outcomes, birth positions, and
      accoucheur type. Logistic regression models were used to examine potential
      confounding and interaction effects of relevant variables. RESULTS: Multiple
      regression analysis revealed a statistically significant association between
      birth position and perineal outcome. Overall, the lateral position was associated
      with the highest rate of intact perineum (66.6%) and the most favorable perineal
      outcome profile. The squatting position was associated with the least favorable
      perineal outcomes (intact rate 42%), especially for primiparas. A statistically
      significant association was demonstrated between perineal outcome and accoucheur
      type. The obstetrician group generated an episiotomy rate of 26 percent, which
      was more than five times higher than episiotomy rates for all midwife categories.
      The rate for tear requiring suture of 42.1 percent for the obstetric category was
      5 to 7 percentage points higher than that for midwives. Intact perineum was
      achieved for 31.9 percent of women delivered by obstetricians compared with 56 to
      61 percent for three midwifery categories. CONCLUSION: Findings contribute to
      growing evidence that birth position may affect perineal outcome. Women's
      childbirth experiences should reflect decisions made in partnership with midwives
      and obstetricians who are equipped with knowledge of risks and benefits of
      birthing options and skills to implement women's choices for birth. Further
      identification and recognition of the strategies used by midwives to achieve
      favorable perineal outcomes is warranted.

PMID- 11843787
TI  - Strategies to address global cesarean section rates: a review of the evidence.
AB  - BACKGROUND: The steadily increasing global rates of cesarean section has become
      one of the most debated topics in maternity care. This paper reviews and reports
      on the success of strategies that have been developed in response to this
      continuing challenge. METHODS: A literature search identified studies conducted
      between 1985 and 2001 from the Cochrane Database of Systematic Reviews, Medline,
      Sociofile, Current Contents, Psyclit, Cinahl, and EconLit databases. An
      additional search of electronic databases for Level 1 evidence (systematic
      reviews), Level 2 (randomized controlled trials), Level 3 (quasi-experimental
      studies), or Level 4 (observational studies) was performed. Selection criteria
      used to identify studies for review included types of study participant,
      intervention, outcome measure, and study. RESULTS: Interventions that have been
      used in an attempt to reduce cesarean section rates were identified; they are
      categorized as psychosocial, clinical, and structural strategies. Two clinical
      interventions, (external cephalic version, vaginal birth after a previous
      cesarean) and one psychosocial intervention (one-to-one trained support during
      labor) demonstrated Level 1 evidence for reducing cesarean section rates.
      CONCLUSIONS: Although the evidence for one-to-one care and external cephalic
      version came from both developed and developing settings, the systematic review
      for vaginal birth after a cesarean was restricted to studies conducted in the
      United States. The effective implementation of the preceding strategies to reduce
      cesarean rates may depend on the social and cultural milieu and on associated
      beliefs and practices.

PMID- 11843788
TI  - Postnatal quality of life assessment: introducing the mother-generated index.
AB  - BACKGROUND: The extent of postnatal morbidity has become increasingly apparent
      over the last 15 years, but currently no tool is available that measures
      postnatal quality of life. This pilot study introduces a subjective tool, the
      Mother-Generated Index, which assesses the woman's quality of life and identifies
      those aspects that are of most concern to her. METHODS: The Mother-Generated
      Index was administered by structured interview to 60 participants at 6 to 8 weeks
      and to 43 participants at 8 months postpartum. Validation was sought through
      concurrent use of the Edinburgh Postnatal Depression Scale, the SF12, and two
      indexes related to maternal and neonatal physical morbidity. The Mother-Generated
      Index gives a primary index (quality of life) score, which is reported here, and
      a secondary index, which identifies the areas considered most important by the
      mother. RESULTS: The primary index was more sensitive at 8 months. The highest
      and lowest quartile scores were compared. Statistically significant differences
      in were found in the mothers' Edinburgh Postnatal Depression scores at 6 to 8
      weeks, and in their Edinburgh Postnatal Depression and SF12 mental component
      scores and their physical morbidity index at 8 months. Although physical problems
      were only a small feature at 8 months, social and psychological issues were
      prominent in both groups. Age, parity, and mode of delivery had no significant
      effect on the women's scores or the areas they identified as most important.
      CONCLUSION: Quality of life of is a complex and personal area, affected by many
      different aspects of health and well-being. From this pilot study the primary
      index appears to be a useful step in assessing a mother's quality of life. It
      identifies which areas of her life are most important to her, and allows her to
      indicate where she would like to see improvements.

PMID- 11843789
TI  - Survey of folk beliefs about induction of labor.
AB  - BACKGROUND: Many folk beliefs concerning the induction of labor are circulated
      among women in their final months of pregnancy. This study sought to identify the
      prevalence of some of these beliefs and whether or not they were more commonly
      shared in certain subsets of the community. METHOD: A survey was conducted of
      women receiving prenatal care at a group of Midwestern urban prenatal clinics.
      Women were asked about exposure to certain recommendations about inducing labor
      and to what extent each recommendation was believed. RESULTS: One hundred and two
      women responded to the survey. Walking and having sex were the activities most
      commonly believed to hasten labor. These beliefs were equally prevalent across
      ages, parities, and levels of education. CONCLUSIONS: Folk beliefs about the
      induction of labor are varied and pervasive in an urban community. A review of
      scientific evidence relating to these beliefs can alert perinatal caregivers to
      potential benefit and harm that could ensue if certain recommendations are
      followed.

PMID- 11843790
TI  - Erb's palsy causation: a historical perspective.
AB  - A better understanding of the forces involved when brachial plexus injury occurs
      has evolved over the past 10 to 15 years. A particular challenge was that all of
      the useful information had to be derived indirectly by identifying associations-a
      challenge that was met by individual researchers who made significant
      observations that, in turn, stimulated others to search for additional findings.
      Gradually the pieces of the puzzle began to form the picture. The significant
      steps in this journey were first, the recognition of the substantial number of
      injuries occurring without concurrent shoulder dystocia; second, the finding that
      a much greater frequency of injury is associated with an ultrashort second stage
      of labor; third, the observations that the injury rate is independent of the
      experience of the birth attendant; fourth, the recognition of the substantial
      numbers of injuries occurring in the posterior arm; and fifth, the anecdotal
      experience of countless delivery attendants, who relate that the forces applied
      in the injured cases were perceived to be no stronger than those applied when no
      injury occurred. We present a historical review for each step in this journey. We
      reviewed all articles published on this subject in Obstetrics and Gynecology and
      the American Journal of Obstetrics and Gynecology and some European journals. The
      period for review primarily covered articles published since 1980. Several
      textbooks on obstetrics and child neurology were also reviewed.

PMID- 11843791
TI  - Evidence-based childbirth only for breech babies?

PMID- 11843792
TI  - Sheila Kitzinger's letter from Europe: what do we tell the children?

PMID- 11843793
TI  - Pregnant and widowed on September 11: the birth community reaches out.

PMID- 11843795
TI  - Use of episiotomy in the United States.

PMID- 11843797
TI  - Immersion in water during first stage of labor.

PMID- 11843800
TI  - Chronic lymphocytic leukaemia involving the gallbladder.

PMID- 11843801
TI  - Pituitary infiltration in B-cell chronic lymphocytic leukaemia.

PMID- 11843802
TI  - Descriptions of blood and blood disorders before the advent of laboratory
      studies.

PMID- 11843803
TI  - Towards molecular medicine; reminiscences of the haemoglobin field, 1960-2000.

PMID- 11843804
TI  - Acute event-related anaemia.

PMID- 11843806
TI  - Intracellular serpins in haemopoietic and peripheral blood cells.

PMID- 11843805
TI  - Gene therapy for haemophilia.

PMID- 11843808
TI  - Idiopathic erythrocytosis--a declining entity.

PMID- 11843809
TI  - Consent in the practice of haematology.

PMID- 11843807
TI  - The phenomenon known as acquired activated protein C resistance.

PMID- 11843810
TI  - An oxaliplatin-based chemotherapy in patients with relapsed or refractory
      intermediate and high-grade non-Hodgkin's lymphoma.
AB  - This study was designed to assess the efficacy and safety of substituting
      cisplatin with oxaliplatin in the DHAP (dexamethasone, cytarabine and cisplatin)
      regimen for patients with relapsed or refractory non-Hodgkin's lymphoma. Twenty
      four evaluable patients with intermediate or high-grade non-Hodgkin's lymphoma
      were treated at 3-weekly intervals with oxaliplatin (130 mg/m2, d 1), cytarabine
      (2 g/m2 for two doses, d 2) and dexamethasone (40 mg, d 1-4). The median age of
      the patients was 58 (range 18-70). Histological subtypes were diffuse large B
      cell, 20; mantle cell, two; anaplastic large cell, one; and peripheral T cell,
      one. The overall objective response rate (RR) was 50% [95% confidence interval
      (CI) = 29-71%] including four complete responses and eight partial responses. RR
      for those patients treated at first relapse was higher than those treated at
      second and subsequent relapse (77% versus 29%). Grade 3 and 4 toxicity was mainly
      haematological: anaemia 17%, neutropenia 75% and thrombocytopenia 75%. No grade 4
      non-haematological toxicity was reported. No significant renal and neurotoxicity
      was demonstrated. Median survival was 10.6 months. Probabilities of 1-year
      progression-free survival and overall survival were 47% (95% CI = 26-66%) and 50%
      (95% CI = 23-72%) respectively. In conclusion, dexamethasone, cytarabine and
      oxaliplatin (DHAX) is a novel combination in salvage therapy for relapsed or
      refractory non-Hodgkin's lymphoma. It has clinically significant activity with an
      acceptable toxicity profile. Lack of renal toxicity makes DHAX an attractive
      cytoreductive regimen before high-dose chemotherapy.

PMID- 11843811
TI  - Prognostic value of positron emission tomography in the evaluation of post
      treatment residual mass in patients with Hodgkin's disease and non-Hodgkin's
      lymphoma.
AB  - The prognostic value of 18F-fluorodeoxyglucose (FDG) positron emission tomography
      (PET) in the assessment of post-treatment residual masses in patients with
      Hodgkin's disease (HD) or non-Hodgkin's lymphomas (NHL) was evaluated. We
      prospectively studied 58 patients with HD (n = 43) or NHL (n = 15) who had post
      therapeutic complete remission with residual masses (CRu) indicated by
      computerized tomography. Analysis of 62 residual locations by FDG-PET was
      performed separately for HD and NHL. Patients with a PET-positive residual mass
      [standardized uptake value (SUV) > 3] had a recurrence rate of 62.5% (5/8
      patients), whereas patients with PET-negative residual mass (SUV < or =3.0)
      showed a recurrence rate of 4% (2/50 patients, P = 0.004). A positive FDG-PET
      study correlated with a significantly poorer progression-free survival (P <
      0.00001). No recurrence occurred in any of the 39 HD patients with a negative PET
      scan (negative predictive value, 100%). Four out of four NHL patients with a
      positive PET study relapsed (positive predictive value, 100%). In conclusion, FDG
      PET is a suitable non-invasive method with a high degree of accuracy in the
      prediction of early recurrence in lymphoma patients with CRu.

PMID- 11843812
TI  - Transformation of T-cell large granular lymphocyte leukaemia into a high-grade
      large T-cell lymphoma.
AB  - We describe a case of T-cell large granular lymphocyte (LGL) leukaemia that
      transformed into a large-cell T-cell lymphoma 11 years from diagnosis. A 29-year
      old asymptomatic female presented in 1989 with lymphocytosis, neutropenia and
      mild bone marrow infiltration. The circulating cells were LGL with a CD2+, CD3+,
      CD8+, CD4-, CD16+, CD56+, CD57- phenotype. In August 2000, she developed fever, a
      large submandibular mass and hepatosplenomegaly. Biochemistry showed abnormal
      liver function tests and raised lactate dehydrogenase (LDH) levels. A serological
      screen for Epstein-Barr virus, cytomegalovirus, human T-lymphotropic virus-I,
      human herpes virus (HHV)-6 and HHV-7 was negative. Histology of the mass was
      consistent with the diagnosis of peripheral T-cell lymphoma composed of large
      cells, and immunohistochemistry showed that the lymphoma cells had a phenotype
      identical to the mature LGL. Molecular analysis with the polymerase chain
      reaction (PCR) demonstrated rearrangement of the T-cell receptor (TCR) gamma
      chain gene with a band of identical size in both bone marrow mature LGL and lymph
      node cells. The patient was treated with CHOP (cyclophosphamide, vincristine,
      doxorubicin and prednisolone), resulting in the disappearance of the mass and
      improvement of the hepatosplenomegaly, LDH and liver abnormalities. She underwent
      splenectomy, and spleen histology showed involvement by T-cell LGL leukaemia with
      no evidence of transformation. This case illustrates that transformation or
      Richter syndrome may occur in a minority of patients with T-cell LGL leukaemia, a
      disease that has a benign clinical course in most cases. This is the first case
      documented by molecular methods of the transformation of the pre-existing clone.

PMID- 11843813
TI  - Complement activation plays a key role in the side-effects of rituximab
      treatment.
AB  - Treatment with rituximab, a chimaeric anti-CD20 monoclonal antibody, can be
      associated with moderate to severe first-dose side-effects, notably in patients
      with high numbers of circulating tumour cells. The aim of this study was to
      elucidate the mechanism of these side-effects. At multiple early time points
      during the first infusion of rituximab, complement activation products (C3b/c and
      C4b/c) and cytokines [tumour necrosis factor alpha (TNF-alpha), interleukin 6 (IL
      6) and IL-8] were measured in five relapsed low-grade non-Hodgkin's lymphoma
      (NHL) patients. Infusion of rituximab induced rapid complement activation,
      preceding the release of TNF-alpha, IL-6 and IL-8. Although the study group was
      small, the level of complement activation appeared to be correlated both with the
      number of circulating B cells prior to the infusion (r = 0.85; P = 0.07) and with
      the severity of the side-effects. We conclude that complement plays a pivotal
      role in the pathogenesis of side-effects of rituximab treatment. As complement
      activation can not be prevented by corticosteroids, it might be relevant to study
      the possible role of complement inhibitors during the first administration of
      rituximab.

PMID- 11843814
TI  - Effect of cytokines on growth and differentiation of leukaemic cells with
      translocation t(6;9)(p23;q34).
AB  - The translocation t(6;9)(p23;q34) is detected infrequently in subtypes of
      haematological malignancies including acute myelogenous leukaemia (AML) and
      myelodysplastic syndrome (MDS). Although the t(6;9) leukaemia is commonly
      associated with bone marrow basophilia, the cytological characteristics of
      leukaemic cells are unclear. In the current study, we examined the in vitro
      effects of several cytokines on growth and differentiation of t(6;9) leukaemic
      cells. Isolated bone marrow mononuclear cells from four patients with t(6;9) (two
      MDS and two AML) were cultured for 14 d in the presence or absence of each
      cytokine. At the end of culture, viable cells were counted, and their histology
      was examined. Bone marrow cells obtained from 22 patients (10 AML, six AML from
      MDS, six MDS) lacking t(6;9) were used as controls. Compared with control
      cultures, significantly higher numbers of blasts appeared in the culture of bone
      marrow cells from t(6;9)-positive patients in response to stimulation with
      granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage CSF (GM
      CSF) or interleukin 3 (IL-3). Stem cell factor (SCF) had little effect.
      Neutrophil counts were also significantly increased in the presence of G-CSF or
      IL-3. SCF and IL-3 were potent in increasing basophil counts from t(6;9)-positive
      cultures. These findings suggest that bone marrow cells obtained from t(6;9)
      patients are highly sensitive to growth- and/or differentiation-promoting
      cytokines. Special attention should be paid to the use of "therapeutic" cytokines
      in these patients.

PMID- 11843816
TI  - Real-time reverse transcription polymerase chain reaction detection and
      quantification of t(1;19) (E2A-PBX1) fusion genes associated with leukaemia.
AB  - A real-time reverse transcription polymerase chain reaction (RT-PCR) method is
      described that enabled the detection and quantification of E2A-PBX1 fusion gene
      transcripts associated with t(1;19). The method was highly reproducible and
      offered exceptional sensitivity at 5 fg of fusion transcript per reaction,
      without the need for a nested PCR primer design. To illustrate the usefulness of
      this new technology the E2A-PBX1 fusion gene transcript expression level for
      several human leukaemia cell lines that are positive and negative for
      cytogenetically detectable t(1;19) was determined. The RCH-ACV had a threefold
      higher expression of E2A-PBX1 transcripts (600 transcripts per cell) than the
      other t(1;19) positive 697 (150 transcripts per cell). The only other cell line
      with detectable E2A-PBX1 was CEM, but the level of expression was < 1 transcript
      per cell.

PMID- 11843815
TI  - Generation of reactive oxygen species is not involved in idarubicin-induced
      apoptosis in human leukaemic cells.
AB  - The anthracycline antibiotic idarubicin (IDA) induces double-stranded DNA breaks,
      the generation of reactive oxygen species (ROS) and apoptosis in human leukaemic
      cells. It is unclear whether the generation of ROS is associated with the
      apoptotic process. Using the T-lymphoblastic leukaemic CEM cell line, we found
      that IDA-induced DNA breaks were correlated with final cell death. The reduction
      in mitochondrial membrane potential (Deltapsim) and the generation of ROS
      occurred simultaneously with IDA-induced activation of caspase-9 and caspase-3.
      Inhibition of caspases by a pan-caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp
      fluoromethyl ketone (Z-VAD-fmk) completely blocked IDA-induced reduction of
      Deltapsim, apoptosis and final cell death. Interestingly, ROS generation was
      significantly enhanced by Z-VAD-fmk. ROS generation was neither caspase dependent
      nor part of the apoptotic process. IDA-mediated reduction in Deltapsim is caspase
      dependent and is not a consequence of the generation of ROS. These results
      indicate that IDA-induced generation of ROS and apoptosis are separate events.
      Inhibition of caspases facilitates IDA-mediated generation of ROS.

PMID- 11843817
TI  - Functional monocyte-derived dendritic cells can be generated in chronic
      lymphocytic leukaemia.
AB  - Chronic lymphocytic leukaemia (CLL) remains an incurable disease. Although modern
      available treatments are able to induce disease regression, relapse almost
      inexorably occurs. Therefore, novel therapeutic strategies aimed at reducing the
      disease relapse rate are very much needed. Among these, the induction of tumour
      associated antigen-specific cytotoxic T lymphocytes (CTL), through either DNA
      vaccines or injection of idiotype pulsed dendritic cells (DCs), has been actively
      investigated with encouraging preliminary results in B-cell malignancies. As the
      CLL B lymphocyte characteristically expresses low amounts of surface
      immunoglobulin (Ig) and T cells from these patients have been reported to display
      impaired functional activity, there are concerns related to the possibility of
      generating specific cytotoxic antitumoral T cells in this disease. In addition,
      no information is presently available regarding the functional ability of CLL
      derived DCs. In the present work, freshly purified monocytes from CLL patients
      and normal donors were induced to differentiate in granulocyte-macrophage colony
      stimulating factor (GM-CSF) and interleukin (IL)-4 serum-free medium and compared
      for their morphological, phenotypic and functional characteristics. Our results
      demonstrate that: (1) functional DCs can be generated from CLL patients with
      similar phenotype and function to those observed from normal donors; (2) in
      contrast to normal control subjects, monocyte-derived DCs from CLL patients
      spontaneously secrete endogenous IL-10; and (3) interferon (IFN)-gamma in
      combination with CD40L plays a major role in priming DCs from CLL patients for IL
      12 and IL-15 production. Overall, these results indicate that it is possible to
      derive functionally competent DCs from circulating monocytes in CLL patients.

PMID- 11843819
TI  - Analysis of clonal B-cell CD38 and immunoglobulin variable region sequence status
      in relation to clinical outcome for B-chronic lymphocytic leukaemia.
AB  - Recent reports suggest that the expression of germline (GL) Ig variable region
      heavy-chain genes (VH) is a negative prognostic factor for B-cell chronic
      lymphocytic leukaemia (B-CLL) patients and that CLL B-cell CD38 expression may be
      a surrogate marker of Ig VH gene status. Currently, however, the usefulness of
      this surrogate marker is controversial. Therefore, our goal was to study the
      ability of CD38 to act as a surrogate marker for Ig VH somatic mutation (SM), and
      to identify differences in overall survival (OS), progression-free survival (PFS)
      and response in B-CLL patients based on these two markers. We first assessed the
      relationship between CD38 expression and Ig VH status on 131 B-CLL patients,
      including 66 patients enrolled in three North Central Cancer Treatment Group
      Trials. Although the mean percentages of CD38+ clonal B cells were significantly
      higher for patients classified as GL versus SM, CD38 was not a reliable marker
      for clonal B-cell SM. Overall, GL patients exhibited significantly shorter OS and
      PFS times than SM patients. Despite the inability of clonal B-cell CD38
      expression to predict Ig VH mutation status, patients with < or =30% CD38+ cells
      did have shorter PFS and OS times than did CLL patients with < 30% CD38+ cells.
      Thus, the relationship between CD38 expression and Ig VH mutation status in B-CLL
      is not straightforward. Nevertheless, analysis in a co-operative group clinical
      trial setting suggests that both B-cell markers alone or in combination may have
      clinical usefulness. These data strongly encourage the study of these biological
      markers as they relate to disease heterogeneity in B-CLL.

PMID- 11843818
TI  - Abnormal growth factor modulation of beta1-integrin-mediated adhesion in chronic
      myelogenous leukaemia haematopoietic progenitors.
AB  - Abnormal progenitor circulation and extramedullary haematopoiesis are
      characteristic features of chronic myelogenous leukaemia (CML). Growth factor
      (GF) and beta1-integrin interactions play an important role in regulation of
      progenitor trafficking to and from the marrow space. CML progenitors demonstrate
      abnormal beta1-integrin-mediated adhesion to fibronectin (FN). In the present
      study we investigated whether GF modulation of beta1-integrin-mediated adhesion
      and migration was altered in CML progenitors. Culture with low concentrations of
      GF enhanced normal progenitor adhesion to FN compared with no GF, but failed to
      enhance CML progenitor adhesion to FN. Similarly, high concentrations of selected
      GF rapidly enhanced beta1-integrin-mediated adhesion of normal progenitors to FN
      through a phosphotidylinositol-3 (PI-3) kinase-dependent mechanism, but failed to
      increase CML progenitor adhesion. Exposure to a BCR-ABL tyrosine kinase inhibitor
      restored GF modulation of CML progenitor adhesion. CML colony-forming cells (CFC)
      demonstrated increased migration across FN-coated transwells compared with normal
      CFC in the absence of GF. The addition of stem cell factor resulted in enhanced
      migration of CML and normal CFC on FN. In conclusion, GF stimulation failed to
      enhance integrin-mediated adhesion but enhanced migration in CML progenitors on
      FN. BCR-ABL induced abnormalities in GF-integrin interactions could contribute to
      abnormal circulation and microenvironmental localization of CML progenitors.

PMID- 11843820
TI  - Enhanced T-lineage acute lymphoblastic leukaemia cell survival on bone marrow
      stroma requires involvement of LFA-1 and ICAM-1.
AB  - The bone marrow (BM) microenvironment supports leukaemia cell survival and
      proliferation. The roles played by adhesive receptor interactions in the survival
      of T-lineage acute lymphoblastic leukaemia (T-ALL) cells on BM stromal cells are
      not well understood. Recently, we have developed an assay that partially
      recapitulates the BM microenvironment using HS-5 BM stromal cells. In this assay,
      the magnitude of ex vivo T-ALL lymphoblast survival predicts patient outcome. We
      examined the molecular basis for cell-cell adhesive events leading to T-ALL
      lymphoblast survival on HS-5 and on donor-derived BM stroma. Lympho cyte function
      associated antigen-1 (LFA-1) on T-ALL cell lines bound intercellular adhesion
      molecule-1 (ICAM-1) on HS-5 monolayers, and survival was inhibited 85-98% with
      monoclonal antibodies directed against LFA-1 or ICAM-1. We compared these results
      with patient-derived T-ALL lymphoblasts co-cultured on either HS-5 BM or normal
      BM monolayers and found that LFA-1 and ICAM-1 were required, but not alone
      sufficient for ex vivo leukaemic cell survival. On normal BM stroma, but not HS-5
      monolayers, two additional adhesion molecules, vascular cell adhesion molecule-1
      (VCAM-1) and E-selectin, were highly expressed and contributed to T-ALL cell
      survival. This is the first report to demonstrate the importance of LFA-1/ICAM-1
      mediated adhesion as a critical event in a cascade of cell surface receptor
      ligand interactions that regulate T-ALL survival in the BM microenvironment.

PMID- 11843821
TI  - Mutation and methylation analysis of the transforming growth factor beta receptor
      II gene in polycythaemia vera.
AB  - Polycythaemia vera (PV) is a myeloproliferative disorder (MPD) thought to result
      from transformation of a haemopoietic stem cell. Transforming growth factor beta1
      (TGF-beta1) is a negative regulator of haemopoietic stem cells, an effect
      mediated by direct binding to TGF-beta receptor II (TGF-beta RII). Reduced levels
      of TGF-beta RII mRNA or protein have been reported in several MPDs including PV,
      suggesting a role for TGF-beta RII in PV. No mutational analysis of the TGF-beta
      RII gene has yet been performed in PV. To investigate whether genetic or
      epigenetic alteration of the TGF-beta RII gene contributes to the pathogenesis of
      PV, we performed mutation and methylation analysis in 15 PV patients. The
      promoter, all seven exons and all intron/exon junctions were studied using single
      strand conformation polymorphism (SSCP) and heteroduplex analysis (HA). In total,
      three single nucleotide polymorphisms (SNPs) were identified. These were located
      in the promoter, intron 2 and exon 5. No acquired mutations were detected in any
      patient sample. We also present a novel method, termed methylation-specific
      strand extension (MSSE), for the detection of methylated CpG dinucleotides. The
      combination of bisulphite modification and MSSE permits rapid analysis of the
      methylation status of CpG dinucleotides in multiple samples. We analysed the
      methylation status of the promoter and of a CpG island within exon 1 in 15 PV
      patients. No aberrant methylation was detected in either of these regions. These
      data demonstrate that neither mutation nor abnormal methylation of the TGF-beta
      RII gene is associated with the pathogenesis of PV. Furthermore, MSSE is a rapid
      and robust approach for assessing the methylation status of a given genomic
      region.

PMID- 11843822
TI  - The clinical and biological effects of thalidomide in patients with
      myelodysplastic syndromes.
AB  - Thirty patients with myelodysplastic syndromes (MDS) were treated with
      thalidomide at 100 mg/d p.o., increased as tolerated to 400 mg/d for 12 weeks.
      Levels of apoptosis, macrophage number, microvessel density (MVD), tumour
      necrosis factor alpha (TNF-alpha), transforming growth factor beta (TGF-beta),
      interleukin 6 (IL-6), vascular endothelial growth factor (VEGF) and basic
      fibroblast growth factor (bFGF) were determined in the serum, bone marrow (BM)
      plasma and BM biopsies before and after therapy. Pretherapy biological
      characteristics of MDS patients were compared with similar studies performed in
      11 normal volunteers. Ten patients demonstrated haematological improvement in the
      erythroid series, six becoming transfusion independent. Responders had a higher
      pretherapy platelet count (P < 0.048) and lower BM blasts (P < 0.013). Median
      time to response was 10 weeks, and four remain in remission beyond a year.
      Pretherapy MDS BMs showed higher MVD (P < 0.001) and TGF-beta (P < 0.03) and
      higher serum TNF-alpha (P < 0.008) compared with normal control subjects. After
      therapy, only BM TGF-beta decreased significantly (P < 0.002). Pretherapy
      haemoglobin was directly related to serum VEGF (P < 0.001) in responders and
      inversely related in non-responders (P < 0.05), suggesting the possibility that
      angiogenesis may be a primary pathology in the former and a consequence of
      anaemia-induced hypoxia in the latter. We conclude that thalidomide has important
      clinical and biological effects in at least a subset of MDS patients, but the
      precise mechanism of its action remains unknown and requires further study
      including a larger number of patients.

PMID- 11843823
TI  - Cyclosporin A combined with vincristine, doxorubicin and dexamethasone (VAD)
      compared with VAD alone in patients with advanced refractory multiple myeloma: an
      EORTC-HOVON randomized phase III study (06914).
AB  - Patients with multiple myeloma (MM) refractory to alkylating agents frequently
      express P-glycoprotein (Pgp), which is associated with the multidrug resistance
      (MDR) phenotype. We have conducted a randomized phase II/III study of the MDR
      reversal agent cyclosporin A combined with VAD (vincristine, doxorubicin,
      dexamethasone) compared with standard VAD in patients with MM stage IIA/IIIA who
      were refractory to or progressive after treatment with alkylating agents. Out of
      81 patients who were randomized, 75 were eligible and evaluable: 34 in the VAD +
      cyclosporin A arm versus 41 in the VAD arm. Toxicities of grade 2-3 were observed
      more often with VAD + cyclosporin A than with VAD only: nausea (30% versus 8%, P
      = 0.015), mucositis (18% versus 5%, P = 0.13), infection (45% versus 35%, P =
      0.50). The treatment results were similar in the two arms: 53% versus 49%
      responded [95% CI (-18.5%, 26.9%)]. The median progression-free survival (PFS)
      was 8.6 months (VAD + cyclosporin A) versus 5.8 months (VAD): [log rank P = 0.16,
      hazard ratio = 0.71, 95% CI (0.44, 1.15)], and median overall survival was 13
      months versus 14.6 months [log rank P = 0.89, hazard ratio = 0.96, 95% CI (0.62,
      1.72)]. The cause of death was progressive disease (85%), toxicity (10%) or other
      (5%). Bone marrow analysis performed in 23 patients showed that the response rate
      was 67% in Pgp-positive versus 55% in Pgp-negative patients. Cyclosporin A
      combined with VAD is relatively well tolerated. There is no effect of cyclosporin
      A on the overall response rate, PFS and overall survival with VAD.

PMID- 11843824
TI  - Identification of P-selectin glycoprotein ligand-1 as a useful marker in acute
      myeloid leukaemias.
AB  - Immunophenotyping is considered to be less valuable in the diagnosis of acute
      myeloid leukaemias (AML) compared with acute lymphoid leukaemias. Here, we
      present data on the use of quantitative flow cytometry (QFC) of P-selectin
      glycoprotein ligand 1 (PSGL-1, CD162) and three-colour immunophenotyping
      including CD162 staining in the identification of myeloid precursors in AML.
      Analysis of normal peripheral blood (n = 20) and normal bone marrow (n = 5)
      samples and on 20 samples from de novo M1, M2, M4 and M5 AML patients
      demonstrated that PSGL-1 is differentially expressed on various mature and
      immature leucocyte subsets. It was found by QFC that neutrophils expressed 26500
      +/- 4500 and monocytes 47200 +/- 9900 copies of PSGL-1 on their surface, whereas
      AML blasts from M1 and M2 AML patients expressed significantly less PSGL-1 (12
      000 +/- 5300) than mature neutrophils (P < 0.001). In M4 and M5 leukaemias,
      however, the amount of PSGL-1 on monocytic precursors is displayed in a fairly
      broad range that is not significantly different from that of mature monocytes (P
      = 0.084). Using three-colour immunophenotyping PSGL-1-dim staining was co
      expressed with CD7 and C34 positivity and PSGL-1 staining intensity on immature
      myeloid cells paralleled with CD45 expression. This would imply a differential
      expression of PSGL-1 during myeloid haematopoietic development and suggests that
      quantification of surface PSGL-1 may aid in differentiating myeloblasts from
      monoblasts by immunophenotyping in different AML subsets.

PMID- 11843825
TI  - X-linked cerebellar ataxia and sideroblastic anaemia associated with a missense
      mutation in the ABC7 gene predicting V411L.
AB  - Two brothers with X-linked ataxia (XLA) were found to have hypochromic red cells
      and increased erythrocyte protoporphyrin despite normal iron stores. The mother
      was unaffected by ataxia and had normal iron stores but showed evidence of some
      red cell hypochromia with heavy basophilic stippling that stained positive for
      iron. Bone marrow biopsy confirmed the presence of ring sideroblasts in one of
      the brothers. The absence of mutations in the ALAS2 gene and the predominance of
      zinc over free protoporphyrin led to a search using a combination of DNA and cDNA
      analysis for the presence of mutations in the ABC7 gene. ABC7 encodes a
      mitochondrial half-type ATP Binding Cassette transporter involved in iron
      homeostasis. The published cDNA sequence was used to search databases for the
      genomic sequence of which 12 exons spanning 23.4 kb were mapped leaving the most
      5' nucleotides unaccounted for. The identified exons and their exon-intron
      boundaries were amplified from DNA while the most 5' sequence including the
      initiation codon was amplified from cDNA of peripheral blood cells. Direct
      sequencing revealed hemizygosity in the brothers and heterozygosity in the mother
      for a G-->C transversion at position 1299 of the published cDNA. This predicts a
      V411L substitution at the beginning of the last of six putative transmembrane
      regions of the protein. Restriction enzyme digestion confirmed the presence of
      this mutation in the three family members but could not detect it in 200 normal
      alleles. An uncle affected by ataxia also carried this mutation. This study
      supports the recently hypothesized involvement of the ABC7 gene in XLSA/A and
      highlights a protein structure region of importance to this syndrome.

PMID- 11843826
TI  - Assessment of antimalarial effect of ICL670A on in vitro cultures of Plasmodium
      falciparum.
AB  - We tested in vitro the antimalarial properties of ICL670A, a newly developed iron
      chelator for the long-term oral treatment of iron overload. Ring-stage
      synchronized cultures of Plasmodium falciparum cultured in human erythrocytes
      were exposed to different concentrations of ICL670A and the conventional iron
      chelator, desferrioxamine B (DFO), for 48 h. Malarial growth was measured by
      incorporation of [3H]-hypoxanthine. ICL670A at 30 micromol/l had marked
      antimalarial activity that was observable by 6 h after beginning the exposure of
      ring-stage parasites to the agent. Over 48 h of culture, malarial growth was
      significantly lower with ICL670A than with DFO at concentrations of both 30
      micromol/l (P = 0.008) and 60 micromol/l (P = 0.001). At 48 h, growth relative to
      control was 53% with ICL670A and 83% with DFO at concentrations of 30 micromol/l,
      and 20% with ICL670A and 26% with DFO at concentrations of 60 micromol/l.
      Standard 50% inhibitory concentrations (IC50s) were similar for ICL670A and DFO.
      Precomplexation with iron completely abolished the inhibitory effect of ICL670A,
      indicating that this new agent, like DFO, probably inhibits parasite growth via
      deprivation of iron from critical targets within the parasite. Further studies to
      address the question of the antimalarial potential of ICL670A in combination with
      classic antimalarials would be of interest.

PMID- 11843827
TI  - Autoimmune haemolytic anaemia triggered by Bartonella henselae infection: a case
      report.
AB  - Bartonella henselae is a hitherto unidentified cause of autoimmune haemolytic
      anaemia. Here we report a case of Coombs-negative autoimmune haemolytic anaemia.
      The episode was preceded by exposure to a cat and a non-specific infectious
      syndrome. Concomitant serum titres of B. henselae antibodies were indicative of a
      recent infection. The case report suggests that B. henselae infection can trigger
      secondary autoimmune haemolytic anaemia.

PMID- 11843828
TI  - Cholelithiasis and Gilbert's syndrome in homozygous beta-thalassaemia.
AB  - Cholelithiasis has been reported with a variable incidence in homozygous beta
      thalassaemia, the reasons for which have only partially been defined. Disease
      associated factors or specific modifier genes may be implicated. We assessed the
      prevalence of cholelithiasis and the effect of co-inherited Gilbert's syndrome
      genotype on its development in 261 thalassaemia major (TM) and 35 thalassaemia
      intermedia (TI) patients. Cholelithiasis was found in 20.3% of TM and in 57.1% of
      TI patients. Its incidence was higher (P < 0.05) in patients homozygous for the
      (TA7) motif in the promoter of the UGT1-A1 gene, the genotype associated with
      Gilbert's syndrome, which seems to be a risk factor for the development of
      gallstones in TM and TI patients.

PMID- 11843829
TI  - A new approach to evaluating intestinal acute graft-versus-host disease by
      transabdominal sonography and colour Doppler imaging.
AB  - An objective and non-invasive method to assess the extent, severity, course and
      prognosis of acute graft-versus-host disease (aGvHD) of the gastrointestinal
      tract would be of great importance. As high-resolution ultrasonography (HRU) and
      colour Doppler imaging (CDI) are used in inflammatory and ischaemic bowel
      diseases, we introduced these techniques to evaluate acute intestinal GvHD. In
      this study, 12 patients with suspected intestinal and/or severe cutaneous aGvHD
      were investigated by HRU and CDI. The structure and thickness of the bowel wall
      and the blood flow pattern in the superior mesenteric artery (SMA) as well as in
      the bowel wall were evaluated. All patients showed thickened bowel wall segments,
      especially in the ileocaecal region. Even in patients without any clinical signs
      of intestinal involvement (3/12), sonographic changes were observed. In six
      patients with severe diarrhoea, sonographic signs of secretory diarrhoea were
      observed. In 4/12 patients, an increased arterial blood flow in the bowel wall
      was demonstrated as a typical characteristic of an inflammatory bowel process. In
      contrast, in 4/12 patients, ischaemic bowel wall lesions with high-resistance
      flow pattern in the SMA were found. These patients did not respond to
      immunosuppressive therapy and died. In conclusion, HRU is a useful tool for
      detecting acute bowel GvHD even before clinical symptoms. Moreover, HRU and CDI
      can be applied to define the severity of aGvHD and to identify patients with a
      poor prognosis.

PMID- 11843830
TI  - Mixed chimaerism is common at the time of acute graft-versus-host disease and
      disease response in patients receiving non-myeloablative conditioning and
      allogeneic stem cell transplantation.
AB  - We report the clinical outcome and results of chimaerism analysis in various cell
      lineages of 30 patients given non-myeloablative conditioning, followed by
      allogeneic stem cell transplantation (SCT). The commonest diagnoses were chronic
      myelogenous leukaemia (n = 11) and solid tumours (n = 11). Twenty-one patients
      received SCT from human leucocyte antigen (HLA)-identical siblings and nine from
      matched unrelated donors. Median patient age was 53 (28-77) years. Four non
      myeloablative protocols were used, including fludarabine (30 mg/m2 x 3-6),
      busulphan (4 mg/kg x 2), cyclophosphamide (Cy) (30 mg/kg/day x 2) or total body
      irradiation (2 Gy), and anti-thymocyte globulin. The patients were analysed by
      polymerase chain reaction (PCR) analysis of minisatellites on days 14, 21 and 28,
      then every other week up to 3 months and monthly thereafter. All samples were
      cell separated for T, B and myeloid cells using immunomagnetic beads. Eighteen
      patients were alive at a median follow-up of 11 (6-20) months. Acute graft-versus
      host disease (GVHD) occurred in 22 patients. Eighteen of the 22 patients with
      acute GVHD showed mixed chimaerism (MC) in the T-cell fraction at the time of
      acute GVHD. However, all patients with acute GVHD showed donor chimaerism (DC) in
      the T-cell fraction median 76 (7-414) days after onset versus three out of eight
      patients without acute GVHD, P < 0.001]. Disease response was diagnosed in 15
      patients, median 100 (37-531) days after SCT. At the time of disease response,
      six out of 15 patients showed MC in the T-cell fraction. In conclusion, mixed
      chimaerism in the T-cell fraction is common at the time of acute GVHD and disease
      response in patients conditioned with non-myeloablative therapy.

PMID- 11843831
TI  - Colour Doppler ultrasonography of a segmental branch of the portal vein is useful
      for early diagnosis and monitoring of the therapeutic course of veno-occlusive
      disease after allogenic haematopoietic stem cell transplantation.
AB  - We report two cases in which visualization of the segmental branch of the hepatic
      portal vein with the colour Doppler ultrasonography (US) technique was useful for
      the early diagnosis of veno-occlusive disease. The change in blood flow in the
      segmental branch of the portal vein occurred 5 and 6 d before the clinical
      criteria were fulfilled in the two cases. Reverse flow in the segmental branch
      began partially in the liver at first, and then spread to the whole liver several
      days later. All the US findings in both cases disappeared after thrombolytic
      therapy.

PMID- 11843832
TI  - Outcome for children after failed transplant for primary haemophagocytic
      lymphohistiocytosis.
AB  - Primary haemophagocytic lymphohistiocytosis is a rare disorder of childhood,
      which is usually fatal without allogeneic stem cell transplantation (SCT). For
      children who lack a matched family or closely matched unrelated donor, SCT using
      haploidentical parental stem cells has been used, but is associated with an
      increased risk of graft failure. The most appropriate subsequent management for
      those children who survive after graft rejection is currently unclear. We report
      the outcome for three such children. After a period of disease quiescence lasting
      4 months to 8 years, disease recurrence and subsequent death occurred in each
      case. Accordingly, a second SCT is recommended.

PMID- 11843833
TI  - Comparison of five platforms for enumeration of residual leucocytes in
      leucoreduced blood components.
AB  - The need for quality control of leucoreduction of blood products has led to the
      development of various methods to count low levels of residual leucocytes. We
      compared five platforms side-by-side: the Nageotte haemocytometer and four based
      on fluorescent staining of nuclei: two flowcytometers (Beckman Coulter, BD
      Biosciences) with methods based on counting beads, a volumetric flow cytometer
      (Partec) and the microvolumic fluorimeter ImagN2000 (BD Biosciences), all
      according to their manufacturers' recommended methods. Analysis of double
      filtered red cell concentrates (RCCs) and platelet concentrates (PCs), spiked
      with various numbers of leucocytes, revealed good linearity for all methods over
      the range of 1.6-32.7 leucocytes/microl, all with r(2) > 0.99. At the rejection
      level of leucocyte-reduced blood components, i.e. 1 x 10(6) per unit
      corresponding with approximately 3.3 leucocytes/microl, the Nageotte
      haemocytometer had low accuracy (0% for RCCs, 56% for PCs), and was relatively
      imprecise [coefficient of variance (CV) of 34% and 30% respectively]. The Partec
      flow cytometer gave good results for RCCs (accuracy 67%, CV 22%), but not for PCs
      (accuracy 0%, CV 25%). The ImagN2000 had an accuracy of 44% for RCCs and 89% for
      PCs, but the precision was variable (CV 32% for RCCs, 15% for PCs). The best
      results were obtained with the Beckman Coulter (RCCs: accuracy 86%, CV 13%, PCs:
      accuracy 67%, CV 16%), and BD Biosciences platforms (RCCs: accuracy 100%, CV 10%;
      PCs: accuracy 89%, CV 11%). We conclude that, at the rejection level of 1 x 10(6)
      leucocytes per unit, the widely used Nageotte haemocytometer performs poorly in
      terms of inaccuracy and imprecision, and that both counting-bead-based, flow
      cytometric methods performed best.

PMID- 11843834
TI  - Early elevation of serum thrombopoietin levels and subsequent thrombocytosis in
      healthy preterm infants.
AB  - To verify pathophysiological mechanisms underlying thrombocytosis in low-birth
      weight (LBW) preterm babies, we evaluated kinetic changes in platelet counts and
      thrombopoietic cytokines including thrombopoietin (TPO), interleukin 6 (IL-6) and
      IL-11 in 24 uncomplicated preterm infants. Platelet counts in cord blood (CB)
      (265 +/- 64 x 10(9)/l) were similar to adult levels, increased by d 14 (473 +/-
      140 x 10(9)/l), and then remained fairly constant. Thrombocytosis (> 500 x
      10(9)/l) was observed in 9/24 (38%) subjects. Mean TPO level in CB was 5.11 +/-
      1.51 fmol/ml, peaked at d 2 (7.64 +/- 3.28 fmol/ml), decreased at d 5 (3.93 +/-
      1.67 fmol/ml), and thereafter kept fairly constant during the remaining neonatal
      period. Compared with term infants, mean TPO levels of preterm infants in CB and
      at d 2 were significantly higher (P < 0.01). There was an inverse correlation
      between platelet counts and TPO levels (r = 0.45, P < 0.001, n = 88). Preterm
      neonates with thrombocytosis had significantly higher TPO values in CB than those
      without thrombocytosis (P < 0.05). There was no significant relationship between
      platelet counts and IL-6. IL-11 was not detectable. These results suggest that an
      early elevation of serum TPO levels is related to the subsequent thrombocytosis
      in LBW preterm infants.

PMID- 11843835
TI  - Polymorphisms of P-selectin glycoprotein ligand-1 are associated with neutrophil
      platelet adhesion and with ischaemic cerebrovascular disease.
AB  - P-selectin glycoprotein ligand (PSGL-1) shares common features with platelet
      glycoprotein Ibalpha. A recently described polymorphism in this receptor that
      results in a variable number of tandem repeats (VNTR) sequence present either 16,
      15 or 14 times (alleles A, B or C) could, similar to GPIbalpha, be functionally
      relevant. The allelic frequency of this polymorphism was investigated in 469
      individuals from the south of Spain, and was similar to that previously described
      in other Caucasian populations: 85% A, 14% B and 1% C alleles. We identified two
      new polymorphisms genetically linked to the C isoform, resulting in the Ser273Phe
      and Met274Val changes. To assess the functional consequence of the polymorphisms
      in the receptor, we performed flow cytometric analysis of P-selectin dependent
      neutrophil-platelet interaction. Neutrophils carrying the shortest C allele and
      the amino acid variations in residues 273 and 274 exhibited a significantly lower
      capacity to bind activated platelets than A/B and A/A samples (mean fluorescence
      intensity of CD42b+ neutrophils 262 versus 303 and 319 respectively, P < 0.05).
      The distribution of the VNTR was analysed in three case-control studies including
      104 cerebrovascular (CVD), 101 coronary heart disease (CHD) and 150 deep venous
      thrombosis (DVT) patients. The results showed that smaller (B and C) alleles seem
      to be associated with a lower risk of developing CVD (P = 0.008) but not to be
      related to CHD or DVT. In conclusion, polymorphisms of the PSGL-1 receptor may
      influence the neutrophil-platelet binding, and represent a risk factor for CVD.

PMID- 11843836
TI  - Some factor VIII exon 14 frameshift mutations cause moderately severe haemophilia
      A.
AB  - Factor VIII's exon 14 codes for its B domain that includes nearly one-third of
      its amino acid sequence that is not necessary for function. Frameshift mutations
      appear to occur more frequently within exon 14 than in other exons. To assess
      exon 14 frameshift mutations and their clinical correlates, a series of
      unrelated, severe or moderately severe haemophilia A patients were screened for
      heteroduplex formation in amplified exon 14 fragments. In 25 families, a
      frameshift mutation was identified by sequencing. Occurrence of haemophilia was
      isolated in 18 of these families. Moderate severity was noted in at least six out
      of 13 families with an A insertion or deletion at one of two sequences where the
      frameshift resulted in a sequence of 8-10 As. Inhibitors occurred in five of the
      other 12 families including one with an A insertion within a sequence of six As.
      Recurrent insertions into an A(8) (codons 1439-1441) or an A(9) (codons 1191
      1194) sequence or of an A deletion from the A(9) sequence are common, recurrent
      causes of haemophilia A that may have a moderately severe phenotype.

PMID- 11843838
TI  - Plasma of patients with Upshaw-Schulman syndrome, a congenital deficiency of von
      Willebrand factor-cleaving protease activity, enhances the aggregation of normal
      platelets under high shear stress.
AB  - Upshaw-Schulman syndrome (USS) is an autosomal recessive disorder characterized
      by repeated episodes of chronic thrombocytopenia and microangiopathic haemolytic
      anaemia (MAHA) that responds dramatically to infusions of fresh frozen plasma
      (FFP). Recent studies have provided consistent evidence that USS is a congenital
      deficiency of plasma von Willebrand factor-cleaving protease (VWF-CPase) activity
      and, therefore, unusually large VWF multimers (UL-VWFMs) are present in the
      plasma. However, the molecular mechanism of the clinical symptoms of USS is not
      well understood. We studied the relationship between UL-VWFMs and
      thrombocytopenia in two USS patients by analysing platelet aggregation using a
      mixture of the patient's plasma and normal washed platelets under high shear
      stress. Our results clearly showed a remarkably enhanced high shear stress
      induced platelet aggregation (H-SIPA) by the patient's plasma. At 24 h after FFP
      infusion (approximately equal to 10 ml/kg body weight), the enhanced H-SIPA
      became almost completely normalized but, 2 d later, it began to return to the
      preinfusion level. These results were in accordance with the change in VWFM
      patterns. The specific effects of enhanced H-SIPA on VWF, platelet glycoprotein
      Ib and endogenous ADP released from platelets upon stimulation were confirmed
      using reagents that specifically inhibit their respective functions. Our present
      results clearly indicate that thrombocytopenia in USS patients is caused by a
      combination of the presence of UL-VWFMs, platelets and high shear stress
      generated in the microcirculation.

PMID- 11843837
TI  - Comparison of intramuscular therapy with Erwinia asparaginase and asparaginase
      Medac: pharmacokinetics, pharmacodynamics, formation of antibodies and influence
      on the coagulation system.
AB  - Asparaginase comes from different biological sources and the various preparations
      have different pharmacokinetic properties, and their tendency to induce side
      effects is different. Erwinia asparaginase (ASNase) has a shorter half-life than
      the Escherichia coli preparations, and it has been reported to be less
      immunogenic than the E. coli preparations and to induce fewer coagulation
      disorders. Children with newly diagnosed acute lymphoblastic leukaemia (ALL) were
      included in this study. Twenty-seven patients were treated with Erwinia ASNase
      (induction therapy 30.000 IU/m2/d i.m. for 10 d, and re-induction therapy 30.000
      IU/m2 twice a week for 2 weeks) and 15 were treated with ASNase Medac (induction
      therapy 1.000 IU/m2/d i.m. for 10 d, and re-induction therapy 5.000 IU/m2 i.m.
      twice a week for 2 weeks). Blood samples were drawn to determine enzyme activity,
      l-asparagine, anti-asparaginase antibodies, and coagulation parameters. After
      i.m. administration, Erwinia ASNase displayed a protracted absorption phase
      compared to ASNase Medac. The mean bioavailability after i.m. administration was
      27% for Erwinia ASNase and 45% for ASNase Medac respectively. Mean trough enzyme
      activities during induction therapy were Erwinia ASNase 1748 IU/l and ASNase
      Medac 272 IU/l, and during re-induction therapy Erwinia ASNase 83 IU/l and ASNase
      Medac 147 IU/l. We conclude that in this setting, therapy with ASNase Medac
      resulted in sufficient treatment during both phases of therapy, whereas treatment
      with Erwinia ASNase resulted in unnecessarily intense therapy during the
      induction phase and insufficient treatment during the re-induction phase. There
      was no significant difference in the incidence of antibody formation, and therapy
      with Erwinia ASNase resulted in a more pronounced influence on the coagulation
      parameters than therapy with ASNase Medac.

PMID- 11843839
TI  - Beriplex P/N reverses severe warfarin-induced overanticoagulation immediately and
      completely in patients presenting with major bleeding.
AB  - In an open non-randomized study, 10 patients with major bleeding and an
      Internationalized Normal Ratio (INR) greater than 14 were treated with 5 mg of
      intravenous vitamin K and 30 iu/kg of a single concentrate containing factors II,
      VII, IX and X (Beriplex P/N; Aventis Behring). The levels of these factors before
      and immediately after treatment were 4.7, 1.6, 8.5 and 1.1 iu/dl and 94, 30, 66
      and 91 iu/dl respectively. The median INR before treatment was greater than 20
      and, after treatment, 1.1. All patients had a satisfactory clinical response with
      immediate cessation of bleeding, and no thromboembolic complications occurred.

PMID- 11843840
TI  - Absence of platelet response after eradication of Helicobacter pylori infection
      in patients with chronic idiopathic thrombocytopenic purpura.
AB  - Eradication of Helicobacter pylori infection has been associated with the
      correction of thrombocytopenia in patients with idiopathic thrombocytopenic
      purpura (ITP). We have analysed the response to eradication of H. pylori in a
      series of 56 adult patients with chronic ITP. Forty patients had H. pylori
      infection (71%) that was eradicated in 23 of 32 evaluable patients (72%).
      Platelet counts did not significantly vary according to H. pylori treatment
      outcome. Three of 56 patients (5%) achieved a partial response attributable to H.
      pylori eradication. Therefore, detection of H. pylori infection should not be
      routinely included in the initial work-up of ITP.

PMID- 11843841
TI  - Serum thrombopoietin levels in relation to disease status in patients with immune
      thrombocytopenic purpura.
AB  - Pre- and post-treatment serum thrombopoietin (TPO) concentration was measured in
      35 patients with immune thrombocytopenic purpura (ITP). Mean post-treatment
      levels were significantly lower (P = 0.02) than pretreatment and not different
      for treatment modality. No significant correlation between pre- or post-treatment
      TPO and platelet counts was demonstrable (R = -0.325, P = 0.056 and R = -0.227, P
      = 0.190 respectively). In patients with very low platelet counts (< or =20 x
      10(9)/l), pretreatment serum TPO was significantly higher than in patients with
      higher counts (P = 0.033). The logarithm of the platelet turnover rate, measured
      in 15 patients, correlated with pretreatment TPO levels (R = 0.64). These
      findings suggest a contributory role for TPO in the mechanism of ITP.

PMID- 11843842
TI  - Homozygosity for the C-->T polymorphism at nucleotide 46 in the 5' untranslated
      region of the factor XII gene protects from development of acute coronary
      syndrome.
AB  - Recently, a C-->T polymorphism at nucleotide 46 in the 5'-untranslated region of
      the factor XII (FXII) gene was shown to be associated with lower levels of FXII.
      To study the impact of this polymorphism on the development of an acute coronary
      syndrome (ACS), we compared 303 patients with ACS and 227 patients with stable
      coronary artery disease (CAD). In the latter group, 54.2% of individuals carried
      wild-type FXII:46C, 37.9% were heterozygous FXII:C46T and 7.9% were homozygous
      for FXII:46T. In contrast, in the ACS group (n = 303), 54.1% were wild-type
      FXII:46C, 42.6% were heterozygous FXII:C46T and only 3.3% carried the homozygous
      FXII:46T genotype. The 2.5-fold lower prevalence of the FXII:46T genotype in
      patients with ACS could indicate a protective effect on the development of ACS
      (odds ratio = 0.4, 95% CI 0.1-0.9) in patients with pre-existing CAD.

PMID- 11843843
TI  - Association of clonal T-cell large granular lymphocyte disease and paroxysmal
      nocturnal haemoglobinuria (PNH): further evidence for a pathogenetic link between
      T cells, aplastic anaemia and PNH.
AB  - There is mounting evidence to suggest that T-cell-mediated suppression of
      haemopoiesis is a pathogenetic mechanism in three bone marrow failure syndromes:
      aplastic anaemia (AA), paroxysmal nocturnal haemoglobinuria (PNH) and
      myelodysplasia (MDS). T-cell microclones can be detected by sensitive polymerase
      chain reaction (PCR)-based methods in all three disorders. Recently, larger
      clonal populations of T-cell large granular lymphocytes (T-LGLs) have been
      observed in some patients with AA and MDS. Here, we report the development of a
      large clonal T-LGL population in a patient with bona fide PNH. In this patient,
      we defined part of the sequence of the T-cell receptor (TCR) beta-chain gene, and
      we have shown that the large T-LGL population emerged from a background of
      multiple smaller T-cell clones. Thus, T-LGL clones in AA, MDS and PNH probably
      expand as a result of antigenic stimulation. It is postulated that the antigen
      driving clonal T-cell proliferations in these disorders exists on haemopoietic
      stem cells.

PMID- 11843844
TI  - Relationship between bone marrow failure syndromes and the presence of
      glycophosphatidyl inositol-anchored protein-deficient clones.
AB  - Because of the insensitivity of the Ham test, paroxysmal nocturnal
      haemoglobinuria (PNH) has been inaccurately viewed as a late clonal complication
      of aplastic anaemia (AA). To clarify the relationship between PNH and marrow
      failure, we tested for the presence of glycosylphosphatidyl-anchored protein
      deficient (GPI-AP) granulocytes in large cohorts of patients with AA,
      myelodysplasia (MDS), and pure haemolytic PNH. A PNH clone was detected in 32% of
      new AA patients and 18% of MDS patients. In serial studies, this proportion did
      not change up to 15 years after diagnosis, suggesting that expansion of aberrant
      cells is an early event (i.e. prior to initial presentation). For all patients
      with a PNH clone, on average 14% of PNH granulocytes were found on presentation
      and 37% at 10 years. Patients with PNH but without cytopenia showed higher
      percentages of GPI-AP-deficient cells than did those with the AA/PNH syndrome.
      After immunosuppression, there was no change in the contribution of PNH clone to
      blood production, arguing against the "immune-escape" theory in PNH. Clinically,
      a high proportion of GPI-AP-deficient cells correlated with marrow
      hypercellularity. GPI-AP-deficient cells were similarly present in patients with
      and without karyotypic abnormalities. Our results indicate that the GPI-AP
      deficient clones show quantitative and kinetic differences between classic
      haemolytic PNH and PNH with marrow failure, in which the evolution rate is low
      later in the course of the disease.

PMID- 11843846
TI  - Cytomegalovirus infection and disease after autologous peripheral blood stem cell
      transplantation.

PMID- 11843845
TI  - Interferon gamma and tumour necrosis factor alpha are overexpressed in bone
      marrow T lymphocytes from paediatric patients with aplastic anaemia.
AB  - Twelve paediatric patients with aplastic anaemia and two groups of normal control
      subjects underwent flow cytometric analysis for intracytoplasmic expression of
      gamma interferon (gamma-IFN) and tumour necrosis factor alpha (TNF-alpha) in bone
      marrow and peripheral blood CD4+ and CD8+ cells. The same cytokines were tested,
      by immunoassay, in culture supernatants from unstimulated bone marrow mononuclear
      cells (MNCs). Marrow CD4+ and CD8+ cells expressing gamma-IFN and TNF-alpha were
      significantly increased in the patients in comparison with normal control
      subjects (P from < 0.05 to < 0.0001 in the different cellular subsets). Patients'
      marrow CD4+ and CD8+ cells containing gamma-IFN and TNF-alpha were significantly
      increased when compared with the same cell fractions from paired peripheral blood
      samples (P from < 0.05 to < 0.0001 in the various cellular subsets). In the
      supernatant of marrow MNCs, gamma-IFN and TNF-alpha were detected in four out of
      eight and five out of eight cases, respectively, whereas neither cytokine was
      traceable in the control subjects. Patients' peripheral blood CD4+ and CD8+ cells
      containing gamma-IFN and TNF-alpha were not significantly increased in comparison
      with those from normal control subjects. Whereas patients with favourable and
      unfavourable outcomes had no significantly different proportions of marrow gamma
      IFN+/CD4+ and gamma-IFN+/CD8+ cells, the percentages of marrow CD4+ and CD8+
      cells containing TNF-alpha were significantly lower in subjects with favourable
      than in those with unfavourable outcome. Overall, these findings show that, in
      aplastic patients, T cells overexpressing gamma-IFN and TNF-alpha concentrate in
      the bone marrow and that intracytoplasmic expression of TNF-alpha in marrow CD4+
      and CD8+ cells is associated with an unfavourable clinical course.

PMID- 11843848
TI  - Biomarker assays in nipple aspirate fluid.
AB  - The noninvasive technique of nipple aspiration as a potential source of
      biomarkers of breast cancer risk was evaluated. The feasibility of performing
      mutagenesis assays, amplifying DNA, and performing protein electrophoresis on
      nipple aspirate fluid was explored. A tool was developed to measure the level of
      discomfort, if any, from this procedure. Twenty-five healthy women (20
      premenopausal and 5 postmenopausal) were enrolled. Fluid was obtained using a
      modified breast pump. Premenopausal women were scheduled for four to six weekly
      aspirations, and postmenopausal women were scheduled for one to two weekly
      aspirations. Mutagenesis assays were performed using the Salmonella (Ames) assay.
      DNA amplification of several microsatellite regions was carried out using
      polymerase chain reaction. Protein was quantified, and two-dimensional protein
      electrophoresis was performed. Overall, fluid was obtained from 80% of the women,
      and the level of discomfort was minimal. Acid hydrolysis of one sample resulted
      in mutagenicity; all six nonhydrolyzed samples were not mutagenic. The ability to
      amplify DNA ranged from 34% to 96%, depending on length of the microsatellite
      region examined. The average protein concentration was 71 microg/mL. Two
      dimensional protein electrophoresis was successfully performed on samples from
      two subjects. Nipple aspiration is a simple technique and is easily learned and
      well tolerated, which yields a reagent useful for a variety of investigations.
      This technique may facilitate the identification and application of biomarkers
      for future breast cancer risk assessment and chemopreventive protocols.

PMID- 11843849
TI  - Sentinel lymph node identification for patients with breast cancer using large
      size radiotracer particles: technetium-99m-labeled tin colloids produced
      excellent results.
AB  - Sentinel lymph node (SLN) biopsies using radioactive tracers have been reported
      to detect the metastatic status of the axillary lymph nodes in breast cancer
      patients. However, the optimal radioactive tracer particle sizes remain to be
      determined. In this study, identification of SLNs with large radiolabeled tin
      colloid particles was evaluated. Seventy-five patients with T1-2, N0 breast
      cancer were enrolled. Two hours prior to surgery, 1 to 2.5 mL technetium-99m
      labeled tin colloid particles were injected around the tumor under
      ultrasonographic guidance. Immediately before the operation, dye fluids were also
      injected around the tumor to increase the interstitial pressure. After axillary
      dissection, lymph nodes with x100 or more uptake of radioactivity than the mean
      of the other lymph nodes are considered to be SLN. All lymph nodes from the
      axillary dissections were pathologically investigated, and the characteristics of
      SLNs were evaluated. SLNs were clearly identified in 74 of 75 patients (98.7%).
      Of 37 patients without SLN metastasis, pathological investigation revealed no
      further involvement of the remaining non-SLNs. The SLNs tended to be larger in
      size, and more than 50% were located in the lower medial site of the axilla. This
      is the first study to show that SLNs could successfully be identified with
      radiolabeled tin colloid particles. When SLNs were negative for metastases, non
      SLNs were always negative.

PMID- 11843851
TI  - Case control study of prognostic markers and disease outcome in inflammatory
      carcinoma breast: a unique clinical experience.
AB  - Inflammatory breast carcinoma (IBC) is a rare but aggressive form of breast
      cancer. In this first-ever study, we investigated the role of nine prognostic
      markers' expression (estrogen receptor [ER], progesterone receptor [PR], p53, C
      erbB-2, epidermal growth factor receptor [EGFR], cathepsin D [CD], proliferating
      cell nuclear antigen [PCNA], DNA ploidy, and S-phase fraction [SPF]) and disease
      outcome in IBC cases compared with the control group. A case control study of IBC
      was conducted on 40 test cases with two controls per case matching age, grade,
      and number of axillary lymph nodes sampled. During 7 years of this study, 10% of
      all patients with breast cancer had IBC. In this study, 84% of IBC cases showed
      positive axillary lymph nodes compared with 63% in control group. The expression
      of nine prognostic markers, that is, ER, PR, p53, C-erbB-2, EGFR, CD, PCNA, SPF,
      and DNA ploidy, was studied by immunohistochemistry and flow cytometry. Hormone
      receptor status showed an inverse correlation (p < 0.05). Among p53, C-erbB-2,
      EGFR, and CD in the IBC group, only p53 showed a significant correlation, with
      70% positivity in IBC versus 48% positivity in the control group (p < 0.05). Much
      higher SPF and PCNA positivity was seen in the IBC group compared with the
      control group (p < 0.05). DNA ploidy also showed a significant correlation
      compared with the control group (p < 0.05). After a median follow up of 18
      months, median overall survival in the IBC group was 1.8 years (range 0.6-5.8
      years) compared with 3.0 years (range 2.5-7.0 years), with a p value of 0.0001.

PMID- 11843850
TI  - Evaluation of monoclonal antibody MIB-1 in the mammary epithelium adjacent to
      fibroadenomas in premenopausal women treated with tamoxifen.
AB  - The purpose of this study was to study the monoclonal antibody MIB-1 in the
      normal breast epithelium adjacent to a fibroadenoma in women in the luteal phase
      of the menstrual cycle who were treated with tamoxifen at doses of 10 and 20 mg
      for 22 days. The proliferative activity of the mammary epithelium adjacent to the
      fibroadenoma was studied by immunohistochemistry on the basis of the monoclonal
      antibody MIB-1 (Immunotech, catalog No. 0505, lot 001). The study was randomized
      and double blind and was conducted on 44 women with fibroadenomas divided into
      three groups: A (n=16, placebo), B (n=15, tamoxifen, 10 mg), and C (n=13,
      tamoxifen, 20 mg). Tamoxifen was administered for 22 days starting on the 2nd day
      of the menstrual cycle, and a biopsy was taken on the 23rd day. Serum estradiol,
      progesterone, sex hormone binding globulin, follicle-stimulating hormone,
      luteinizing hormone, and prolactin were measured before treatment (21st and 24th
      day of the previous menstrual cycle) and on the day of the biopsy. The mean
      percentage of stained nuclei per 1,000 cells was 9.2 in group A, 4.5 in group B,
      and 3.2 in group C. The Fisher's test revealed that tamoxifen significantly
      reduced MIB-1 at doses of 10 and 20 mg compared with the placebo group (p <
      0.0001), with no significant differences between doses in terms of proliferative
      activity (p=0.21). Groups B and C presented a significant increase in
      progesterone (p=0.038), estradiol (p < 0.001), and sex hormone binding globulin
      (p=0.001) levels. Elevation of serum follicle-stimulating hormone concentration
      (p=0.0045) and a fall in prolactin levels (p=0.0055) were observed. We conclude
      that tamoxifen significantly reduced the proliferative activity of the mammary
      epithelium at the doses of 10 and 20 mg/day.

PMID- 11843852
TI  - Diagnosis of metachronous contralateral breast cancer.
AB  - The purpose of this study was to compare the characteristics of primary breast
      cancers (PBCs) and metachronous contralateral breast cancers (MCBCs). Between
      1984 and 1996, 236 women treated with curative intent for PBC who developed a
      MCBC >6 months after initial diagnosis (without previous evidence of distant
      metastases) were retrospectively evaluated for clinical and pathologic
      characteristics and method of diagnosis of their tumors. There were more
      noninvasive cancers among the MCBCs than the PBCs (11.4% and 5.1%, respectively,
      p < 0.02). Among the invasive cancers, the mean size of the MCBCs was smaller
      than the PBCs (1.94 versus 2.55 cm, p < 0.001). MCBCs were more likely than PBCs
      to be mammographically detected (46.2% versus 19.9%, p < 0.001). Tumor size was
      correlated with the method of diagnosis. The mean tumor size was 1.39, 2.02, and
      2.69 cm for mammogram-, physician-, and patient-detected tumors, respectively.
      Among patients having axillary lymph node dissections, mammogram- and physician
      detected tumors were less likely to have lymph node metastases than patient
      detected tumors (22.0% versus 41.2%, p < 0.005). Regular follow-up of breast
      cancer patients diagnoses MCBCs when they are smaller and less likely to have
      nodal metastases than PBCs mainly because of early mammographic detection.

PMID- 11843853
TI  - Malignant phyllodes tumor.
AB  - The study aims to evaluate the survival and prognosis of patients with malignant
      phyllodes tumor. Between 1982 and 1998, 37 women with malignant phyllodes tumor
      were treated at the Regional Cancer Center, Trivandrum. Twelve patients were
      recurrent. Survival was estimated using the Kaplan-Meier method. Patient,
      disease, and treatment factors were compared using log-rank test. The Cox
      proportional hazard model was employed to identify the prognostic factors. Thirty
      six patients had surgery. Twenty-five patients received postoperative
      radiotherapy, and 2 received chemotherapy in addition. The median follow-up was
      43 months (range 1-170 months). Eight patients failed locally, and 7 of these
      were successfully salvaged by surgery. The 5-year overall survival was 74.2% (95%
      CI, 0.44 to 0.89), whereas 5-year disease-free survival was 59.6% (95% CI, 0.39
      to 0.7). The margin of surgical excision was found to be the only independent
      prognostic factor (p=0.003). However, patients with tumor size more than 5 cm
      (hazard ratio 2.9) were found to have increased hazard, whereas those receiving
      adjuvant radiotherapy (hazard ratio 0.6), married women (hazard ratio 0.4), and
      those women over the age of 35 years (hazard ratio 0.7) showed a decreased
      hazards. Cystosarcoma phyllodes is a rare malignancy of the female breast.
      Surgery with adequate margins is the primary treatment. Adjuvant radiotherapy
      appears to improve the disease-free survival.

PMID- 11843855
TI  - Ulcerative breast cancer: case report and review of management.
AB  - In the literature, there is an astonishingly small amount of information on
      specific treatment modalities of locally advanced, ulcerated breast cancer. Here
      we present a case report and a literature review on ulceration in breast cancer.
      An older, so far untreated woman with complete ulcerative destruction of her
      right breast was inoperable because of the extent of the tumor. Primary
      anthracycline-based chemotherapy and hormonal therapy led to major tumor
      shrinkage with complete ulcer healing, which was maintained for nearly 2 years.
      There is increasing evidence from the literature that primary chemotherapy may
      particularly benefit patients with inoperable ulceration, as also illustrated by
      our case.

PMID- 11843854
TI  - Mammographic appearance of ductal carcinoma in situ does not reliably predict
      histologic subtype.
AB  - Histologic subtypes of ductal carcinoma in situ (DCIS) have been correlated with
      disease prognosis. There are conflicting reports on whether the grade of DCIS can
      be predicted by the morphology of calcifications seen on mammography. We
      undertook this study to determine whether the grade of DCIS can be reliably and
      accurately determined by mammography prior to excisional biopsy. Ninety
      consecutive cases of DCIS from 1993 to 1996 were identified, of which 75 cases
      had mammograms available for review. Any lesion with invasion was excluded. The
      mammogram showed only a mass in 10 of 75 cases, a mass and calcifications in 3 of
      75 cases, and calcifications alone in 62 of 75 cases. Three board-certified
      radiologists with special expertise in mammography reviewed and categorized the
      mammographic findings as well, intermediate or poorly differentiated DCIS without
      knowledge of the histologic diagnosis. Histologic grading was performed without
      knowledge of the mammographic finding. Receiver operating curves (ROCs) were
      computed for each of the radiologists. For microcalcifications, the ROC
      comparisons of the radiologists' opinions of tumor grade and random chance were
      not significantly different. In those cases with available magnification views,
      the grade assessment did not change significantly. If only a mass was present on
      mammography, well-differentiated DCIS was the predominant histologic subtype. A
      histologic grade of DCIS cannot accurately be determined prospectively based on
      the mammographic appearance of microcalcifications. However, if only a mass is
      present, this is more likely to represent well-differentiated DCIS.

PMID- 11843856
TI  - SiteSelect: minimally invasive excision of breast lesions.
AB  - The goal of screening mammograms is to provide early detection of breast cancer.
      As mammography technology improves, the ability to detect smaller and smaller
      suspicious lesions is increased. However, as mammography cannot always
      differentiate between malignant and benign lesions, biopsies are often needed.
      With the decreasing size of lesions seen on mammography, the size of the biopsy
      specimen needed for diagnosis also decreases. Thus, a smaller amount of normal
      breast tissue needs to be removed during a biopsy. For a majority of the small
      lesions, excision with a small margin of normal breast tissue is sufficient for
      diagnosis. The SiteSelect procedure utilizes stereotactic guidance to excise
      completely a tumor that is noted on a mammogram. The procedure can be performed
      under local anesthesia through a minimal incision (usually 1.5 cm). The
      SiteSelect biopsy procedure completely excises small tumors noted on the
      mammogram with minimal trauma to the breast tissue and with excellent cosmetic
      results. It is well tolerated by patients. For tumors requiring only local
      excision, such as atypical ductal hyperplasia or lobular carcinoma in situ, the
      SiteSelect procedure may be the only diagnostic procedure required.

PMID- 11843857
TI  - A 19 year old with complete androgen insensitivity syndrome and juvenile
      fibroadenoma of the breast.
AB  - We report a case of a 19-year-old female with complete androgen insensitivity
      syndrome (CAIS) who was diagnosed with a juvenile fibdroadenoma of the breast.
      The patient presented at age 18 with primary amenorrhea. She had been raised as a
      female and went through thelarche at age 13 and adrenarche at age 14. She had two
      sisters and three maternal aunts with androgen insensitivity syndrome. Physical
      exam revealed that the patient had no cervix, and a pelvic sonogram confirmed
      that the uterus was absent. Genetic analysis revealed a 46 XY karyotype.
      Bilateral intra-abdominal testes were noted on ultrasound and subsequently
      removed. She was placed on synthetic estrogen replacement therapy. Roughly 1 year
      following orchiectomy, the patient noticed an enlarging mass in her right breast.
      Physical exam revealed a roughly 5 cm mobile mass in the upper portion of the
      nipple-areolar complex. Ultrasound showed a solid mass consistent with a
      fibroadenoma. Because of the size of the lesion and the patient's hormonal make
      up, a fine needle aspirate was obtained. Cytopathology showed large cohesive
      sheets of ductal epithelial cells, scattered histiocytes, numerous bare nuclei,
      fragments of fibrous tissue and metachromatic stroma. Some of the stroma was
      noted to be cellular. The tumor was subsequently excised. Microscopically, the
      lesion had epithelial and stromal hyperplasia consistent with a fibroadenoma.
      Phyllodes-like qualities of large size, increased stromal cellularity, and
      intracanalicular growth ("leaf-like projections") were noted; however, the
      pathologist found that the florid epithelial hyperplasia and the patient's young
      age were more compatible with a juvenile fibroadenoma. We describe what we
      believe to be the first report of a patient with CAIS and a fibroadenoma of the
      breast. The hormonal imbalance typically found in these patients, combined with
      the fact that most individuals with CAIS receive exogenous estrogen therapy,
      suggests that there may be a relatively high incidence of fibroadenoma in these
      patients.

PMID- 11843858
TI  - Tamoxifen in the management of pseudoangiomatous stromal hyperplasia.
AB  - Pseudoangiomatous stromal hyperplasia (PASH) is a relatively uncommon histologic
      finding in breast specimens. The clinicopathologic spectrum of this disease
      entity can range from a focal nonsignificant microscopic finding to a dominant
      palpable breast mass. To confirm the diagnosis, a biopsy is required primarily to
      distinguish PASH from a low-grade angiosarcoma. The mammographic description of
      PASH is a round or ovoid, circumscribed or partially circumscribed mass. The
      sonographic feature is a hypoechoic mass. PASH is similar to a fibroadenoma in
      clinical and imaging features. Progressive breast enlargement associated with
      engorgement, cyclical breast pain, and burning sensation is of significant
      concern for some women. The management of the palpable mass and associated
      symptoms has included excisional biopsy, often leading to recurrent excisions and
      even mastectomy. This report documents an impressive response to tamoxifen in a
      patient with PASH presenting with breast enlargement, pain, and breast masses. To
      our knowledge, there are no reports on the use of tamoxifen or other selective
      estrogen receptor modulators in the management of this benign breast condition.

PMID- 11843859
TI  - Pseudomicrometastasis in sentinel lymph node-multinucleated macrophage mimicking
      micrometastasis.

PMID- 11843860
TI  - Tamoxifen-induced cirrhotic process.

PMID- 11843861
TI  - Who's listening? Experiences of women with breast cancer in communicating with
      physicians.
AB  - The purpose of this qualitative study was to describe communication behaviors and
      attitudes of physicians that were most important to women living with breast
      cancer. Two focus group sessions were conducted, 1 month apart, involving 15
      women who were members of a community-based breast cancer support group in
      Vancouver, British Columbia, Canada. Group dialogue was audiotaped, and notes
      were taken at each session by the coinvestigators, also members of the support
      group. Audiotapes, coinvestigators' written notes from the two focus group
      sessions, and the written homework assignments were used in the qualitative data
      analysis. Conceptual themes were identified and grouped to discern patterns
      within the data. The women were asked the following: (a) What were the most
      helpful things your doctor said or did at the time of your diagnosis? (b) What
      does a good intervention feel or look like? They were then asked to describe
      behaviors and attitudes they would like to influence in medical students who
      might later be communicating with women facing a diagnosis of breast cancer and
      to indicate which behaviors and attitudes they felt were most important. Women's
      positive experiences with physicians were characterized by communication based on
      active listening, awareness of the women's knowledge of their illness, honesty,
      and partnership. Physicians who showed interest in their patients as persons and
      who used touch to communicate caring were perceived as supportive communicators.
      Not surprisingly, there were similarities between the participants' positive
      experiences with their own physicians and the behaviors and attitudes desired in
      future physicians. Once again, "listening" was ranked as most important, followed
      by willingness to discern the individual patient's knowledge level.

PMID- 11843862
TI  - "Routine" weekly blood counts during breast irradiation for early stage cancer:
      are they really necessary?
AB  - The present investigation analyzed the weekly blood count assays of 73 women
      receiving breast irradiation after organ-preserving surgery for early stage
      cancer. With regard to leucopenia and anemia, grade 1 toxicity occurred in 26%
      and 21%, respectively, of the cases. Thrombocytopenia of any degree and grades 2
      4 leucopenia or anemia were either not seen or were minimally observed. Most of
      the patients who experienced grade 1 or grade 2 toxicity had received
      preirradiation chemotherapy. We stress the importance of a baseline blood count
      recording prior to breast irradiation and the need for further study to define
      better the population for whom continuous weekly blood count determinations might
      prove to be useful.

PMID- 11843863
TI  - No involvement of the calcium channel gene (CACNA1A) in a family with cluster
      headache.

PMID- 11843864
TI  - The hemicrania continua diagnosis.
AB  - More than 16 years after the first description of hemicrania continua (HC), its
      aetiology and pathogenesis remain obscure. Clinically, HC is considered a
      syndrome with two pivotal characteristics: (i) strictly unilateral (moderate,
      fluctuating, relatively long-lasting) headache; and (ii) absolute response to
      indomethacin. HC is further characterized by some ancillary, but mostly
      "negative", features such as: (iii) relative paucity of accompaniments; and (iv)
      lack of precipitating factors. The female preponderance is also remarkable,
      although not diagnostic in the solitary case. Finally, a non-specific, but
      remarkable feature is the temporal pattern. HC may present as a remitting or
      chronic (continuous) headache. In HC, unilaterality and absolute response to
      indomethacin are considered crucial diagnostically. Existing controversy, such as
      regarding atypical features, particularly the so-called "HC resistant to
      indomethacin", is discussed. The nature of hemicrania with negative indomethacin
      response remains most unclear; it may not belong to the HC cycle at all.
      Accordingly, we propose that the typical clinical picture of HC, including an
      absolute response to indomethacin, be termed Hemicrania continua vera. More or
      less analogous, but indomethacin-resistant, clinical pictures can provisionally
      be termed Hemicrania generis incerti (of undetermined nature), provided other
      diagnostic possibilities have been ruled out. The differential diagnosis of HC
      vs. other unilateral headaches is commented on. Previous attempts at
      classification of HC into the group chronic daily headache (CDH) are discussed.
      The only acceptable "link" of HC with the other headaches classified as CDH is
      the temporal pattern (which is a non-specific feature). HC is probably
      pathophysiologically different from the others disorders classified under CDH.
      Conversely, HC and chronic paroxysmal hemicrania share many common features,
      including the absolute response to indomethacin. HC should probably be included
      in the IHS group 3.

PMID- 11843865
TI  - The Migraine Disability Assessment (MIDAS) questionnaire: translation and
      reliability of the Italian version.
AB  - We have developed and tested an Italian version of the Migraine Disability
      Assessment (MIDAS) questionnaire, an established instrument for assessing
      headache-related disability. A multistep process was used to translate and adapt
      the questionnaire into Italian, which was then tested on 109 Italian migraine
      without aura patients, 86 (78.9%) of whom completed the form a second time 21
      days later. Overall MIDAS score had good test-retest reliability (Spearman's
      correlation 0.77), closely similar to that found in English-speaking migraineurs,
      and individual responses were also satisfactorily reliable. Internal consistency
      was good (Cronbach's alpha 0.7). These findings support the use of the MIDAS
      questionnaire as a clinical and research tool with Italian patients.

PMID- 11843866
TI  - CACNA1A gene polymorphisms in cluster headache.
AB  - Cluster headache (CH) is a primary headache disorder where the aetiological and
      pathophysiological mechanisms still are largely unknown. An increased risk of CH
      in first- and second-degree relatives suggests the importance of genetic factors.
      Mutations of the P/Q type calcium channel alpha 1 subunit (CACNA1A) gene on
      chromosome 19p13 have been shown to cause several neurological disorders with a
      wide clinical spectrum, mainly episodic diseases. Missense mutations of the gene
      cause familial hemiplegic migraine (FHM) and it is also likely to be involved in
      the more common forms of migraine. The CACNA1A gene is thus a promising candidate
      gene for CH. In this study we performed an association analysis of an intragenic
      polymorphic (CA)n-repeat with marker D19S1150 and a (CAG)n-repeat in the 3'UTR
      region, in 75 patients with CH according to IHS criteria and 108 matched
      controls. Genotypes and allele frequencies were similarly distributed in patients
      and controls. Linkage disequilibrium between the two markers was similar in
      patients and controls. We conclude that an importance of the CACNA1A gene in
      sporadic CH is unlikely.

PMID- 11843867
TI  - No involvement of the calcium channel gene (CACNA1A) in a family with cluster
      headache.
AB  - It is very likely that genetic factors play a role in the pathophysiology of
      cluster headache (CH). As CH shares its paroxysmal character with migraine, and
      migraine has been described in coexistence with CH in some families, we
      hypothesized that both diseases might share a genetic aetiology. In this study,
      we tested whether the migraine CACNA1A gene on chromosome 19 is involved in CH in
      an extended pedigree. Haplotype analysis did not reveal an obvious disease
      haplotype, and SSCP analysis of all 47 exons of the CACNA1A gene did not reveal a
      causative mutation. CH in this family is not caused by mutations in the CACNA1A
      gene.

PMID- 11843868
TI  - Trigeminal nociception-induced cerebral Fos expression in the conscious rat.
AB  - Little is known about trigeminal nociception-induced cerebral activity and
      involvement of cerebral structures in pathogenesis of trigeminovascular headaches
      such as migraine. Neuroimaging has demonstrated cortical, hypothalamic and
      brainstem activation during the attack and after abolition with sumatriptan. This
      has led to the conclusion that the dorsal raphe and locus coeruleus may initiate
      events that generate migraneous headache. Using a conscious rat model of
      trigeminal nociception and cerebral Fos expression as histochemical markers of
      neuronal activity, we characterized the pattern of brain activity after noxious
      trigeminal stimulation with capsaicin (250 and 1000 nm). A significantly
      increased Fos immunoreactivity was found in the trigeminal nucleus caudalis
      (layers I and II), the area postrema, the nucleus of the solitary tract, the
      parvicellular reticular nucleus, the locus coeruleus, the parabrachial nucleus
      and the raphe nuclei. In addition, the ventrolateral periaqueductal grey, the
      intralaminar thalamic and various hypothalamic areas, showed an enhanced Fos
      expression after the intracisternal administration of capsaicin. Other responding
      areas were the amygdala, the upper lip and forelimb regions of the primary
      somatosensory cortex, and the insula. Many of these areas participate in (anti)
      nociception, although we cannot exclude the possibility that in conscious animals
      the pain-associated physiological and behavioural responses that are an intrinsic
      and necessary part of coping with pain have generated the increased Fos
      expression. Trigeminal stimulation-induced locus coeruleus, dorsal raphe and
      hypothalamic activation are opposed to a suggested pathogenic role of these
      nuclei in migraine and cluster headache, respectively.

PMID- 11843869
TI  - Posture-related headaches and pachymeningeal enhancement in CSF leaks from
      craniotomy site.
AB  - Cerebrospinal fluid (CSF) leak is recognized to cause headaches that typically
      but not invariably have orthostatic features (present in upright posture,
      relieved by recumbency). Head magnetic resonance imaging (MRI) typically shows
      diffuse pachymeningeal enhancement. A 24-year-old woman, after resection of a
      right temporoparietal glioma, developed CSF leak from the craniotomy site,
      resulting in subgaleal fluid collection and associated with diffuse
      pachymeningeal gadolinium enhancement as well as posture-related headaches. The
      headaches, however, were present in a recumbent position and relieved after
      several minutes of being in an upright position. It is postulated that CSF leak
      took place when the patient was recumbent and ceased when she was upright, a
      position in which there is decrease in intracranial pressure. After cessation of
      the leak, along with disappearance of subgaleal collection of CSF, both the
      headaches and the pachymeningeal enhancement resolved.

PMID- 11843870
TI  - Chronic daily headache in Taipei, Taiwan: prevalence, follow-up and outcome
      predictors.
AB  - We conducted a two-stage population-based headache survey among subjects aged >
      or = 15 in Taipei, Taiwan. Subjects with chronic daily headache (CDH) in the past
      year were identified, interviewed and followed-up. CDH was defined as a headache
      frequency > 15 days/month, with a duration > 4 h/day. Of the 3377 participants,
      108 (3.2%) fulfilled the criteria for CDH, with a higher prevalence in women
      (4.3%) than men (1.9%). TM was the most common subtype (55%), followed by CTTH
      (44%). Thirty-four per cent of the CDH subjects overused analgesics. At the 2
      year follow-up, 35% of the CDH subjects still had CDH. The significant predictors
      for persistent CDH at follow-up included: older age ( > or = 40 years) (RR =
      2.4), CDH onset after 32 years (RR = 1.8), CDH duration > or = 6 years (RR =
      2.0), medication overuse (RR = 1.8), and "daily" headache (RR = 2.1). We found
      that CDH is not uncommon in the community and its prevalence is similar among
      different populations. Older subjects and those with medication overuse may have
      a more protracted course of illness.

PMID- 11843871
TI  - Leukocyte mitochondrial DNA A to G polymorphism at 11084 is not a risk factor for
      Japanese migraineurs.
AB  - Mitochondrial dysfunction has been reported in patients with migraine. We
      investigated leukocyte mitochondrial DNA 11084 A to G polymorphism in 166
      Japanese migraineurs and 483 Japanese controls. The migraine group consisted of
      43 patients suffering from migraine with aura (MWA) and 123 from migraine without
      aura (MOA). The frequency of the transition was 7.2% (12/166) in the migraine
      group and 7.3% (35/483) in the controls. The frequency of the transition was 4.7%
      in MWA and 8.1% in MOA. There was no significant difference among the groups (chi
      square test). The mitochondrial DNA 11084 A to G transition was more common in
      Japanese subjects than reported in Caucasians; however, this polymorphism is not
      a genetic risk factor for migraine in Japanese patients.

PMID- 11843872
TI  - Recurrent Lilliputian hallucinations as visual aura symptom in migraine.
AB  - Since her early 30s a 72-year-old female migraine sufferer has experienced
      recurrent episodes of Lilliputian hallucinations occurring at the peak of her
      severe migraine attacks and lasting between 2 min and 5 min, suggesting that her
      miniature hallucinations represent a visual migraine aura symptom. The existence
      of Lilliputian hallucinations of a migrainous nature is confirmed by four similar
      case reports reviewed from the migraine literature. The occurrence of similar
      Lilliputian hallucinations in the syndrome of peduncular hallucinosis, due to
      mesencephalic and/or thalamic lesions, supports the notion that the patient's
      recurrent Lilliputian hallucinations might have been aura symptoms of basilar
      migraine.

PMID- 11843873
TI  - Melatonin in the preventive treatment of chronic cluster headache.
AB  - Cluster headache is a stereotypic headache disorder marked by short-lasting bouts
      of severe unilateral head pain and associated autonomic symptoms. Almost
      pathognomonic of this condition are nocturnal attacks that usually occur during
      the first random eye movement sleep phase of the evening. Melatonin levels have
      been found to be decreased in cluster headache patients. A lack of melatonin
      secretion may predispose the cluster sufferer to nocturnal and, possibly, daytime
      attacks. Leone et al. demonstrated that melatonin could rapidly alleviate cluster
      attacks, but only in episodic cluster patients. We report two chronic cluster
      headache patients who had both daytime and nocturnal attacks that were alleviated
      with melatonin.

PMID- 11843874
TI  - A case of a patient with SUNCT syndrome treated with Jannetta procedure.

PMID- 11843875
TI  - Orthostatic headache: an unusual presentation of a skull base tumour.

PMID- 11843876
TI  - Cold-stimulus headache.

PMID- 11843881
TI  - Comparison of the reticulocyte mode of the Abx Pentra 120 Retic, Coulter General
      S, Sysmex SE 9500, Abbott CD 4000 and Bayer Advia 120 haematology analysers in a
      simultaneous evaluation.
AB  - The Abx Pentra 120 Retic, Coulter General-S, Sysmex SE 9500, Abbott Cell Dyn 4000
      and Bayer Advia 120 were evaluated simultaneously in a general hospital
      laboratory. Linearity, precision, sample stability, carry-over and comparability
      of the reticulocyte mode were determined following International Council for
      Standardization in Haematology guidelines for the evaluation of blood cell
      analysers. All analysers showed good results for dilution, stability and carry
      over testing. The between-batch coefficient of variation of the General-S was
      high compared to the other analysers evaluated. Multiple correlation studies
      showed good agreement for all analysers in the normal and high reticulocyte
      range, with correlation coefficients above 0.7. Multiple correlation studies for
      reticulocytopenic samples (< 15.109/l) were less satisfactory, with a wider range
      of correlation coefficients (r-values 0.0-0.9). Overall, the General-S, SE 9500
      and Advia 120 gave lower reticulocyte counts than the Pentra 120 Retic and CD
      4000. Reagent costs were also evaluated. Reagent consumption was close to the
      manufacturers' specifications for the SE 9500 (Search reagent), CD 4000 (CD
      Retic) and Advia 120 (Retics) but was higher than stated for the Pentra 120 Retic
      (Retix), General-S (Retic kit) and SE 9500 (Sheath reagent). Our results show
      that these new generation haematology analysers will meet the needs of hospital
      laboratories for reliable and cost-effective reticulocyte counting.

PMID- 11843882
TI  - Respiratory changes in human red cells.
AB  - To investigate physiological respiratory changes in human red cells, we measured
      automated red cell parameters in samples from the pulmonary and radial arteries
      of 86 patients undergoing aorto-coronary bypass and from the pulmonary artery and
      the aorta in 23 patients. Our results showed higher mean corpuscular volume
      (88.53 +/- 5.06 fl vs. 88.12 +/- 4.94 fl, P < 0.000001), haematocrit (0.369 +/-
      0.039 vs. 0.367 +/- 0.038, P < 0.0005), red cell distribution width (43.38 +/-
      4.16 vs. 43.04 +/- 4.05 fl, P < 0.000001) and a lower mean corpuscular
      haemoglobin concentration (338.3 +/- 15.9 vs. 339.9 +/- 16.8 g/l, P < 0.005) in
      pulmonary arterial as compared to radial arterial blood. There were no
      differences with respect to haemoglobin concentration, red blood cell count, or
      mean corpuscular haemoglobin. Similar differences were observed between pulmonary
      arterial and aortic blood. Our results suggest cyclic respiratory modifications
      of red cell parameters attributable to the CO2 Jacobs-Stewart cycle.

PMID- 11843883
TI  - High serum cobalamin levels in the clinical setting--clinical associations and
      holo-transcobalamin changes.
AB  - Whereas low cobalamin levels have been studied intensively, systematic
      information about high levels, especially in the clinical setting, is scarce.
      Therefore, a prospective comparison was done of 60 patients with high cobalamin
      levels and 75 with normal levels obtained by a hospital laboratory over a 2.5
      month period. Associations with clinical disorders and laboratory test results
      were examined. Transcobalamin (TC) I and II were measured, especially the
      holoproteins (TC carrying circulating endogenous cobalamin) which were
      fractionated with microfine silica powder. High cobalamin levels (> 664 pmol/l; >
      900 ng/l) occurred in 94 of 670 consecutive clinically requested assays (14%).
      The only independently significant associations with a high cobalamin level were
      renal failure among the clinical disorders (P=0.01), elevated serum creatinine
      (P=0.0001) and diminished albumin (P=0.0002) levels among laboratory tests. Both
      holo-TC I and holo-TC II levels were increased in renal failure (P=0.0001) but
      the increase was relatively greater in holo-TC II. The results indicate that high
      cobalamin levels are more frequent than low ones in clinical practice and appear
      to be associated often with renal failure. The elevation of both holo-TC II and
      holo-TC I suggests that several mechanisms are operative. The accumulation of
      holo-TC II suggests that cellular uptake of cobalamin by the abundant TC II
      receptors in the kidney may be impaired. The much better known association of
      high cobalamin levels with leucocytic disorders is rare, and no association was
      seen with liver disease.

PMID- 11843884
TI  - Molecular analysis of beta-thalassaemia patients in a high incidence area of
      southern Italy.
AB  - The prevalence of eight mutations in 84 patients with beta-thalassaemia major and
      in 16 subjects with thalassaemia intermedia was investigated. All of the patients
      were Italian, originating from Eastern Sicily (Messina area) and some Calabrian
      regions. Genomic DNA was amplified by polymerase chain reaction (PCR). DNA
      molecular investigations were performed by allele-specific oligonucleotide (ASO)
      hybridization, to identify the following beta-thalassaemia mutations: CD39 (C-T),
      IVS1-110 (G-A), IVS1-6 (T-C), IVS1-1 (G-A), IVS2-745 (C-G), IVS2-1 (G-A), -87 (C
      G), CD6 A (-A). Our data underline that in thalassemia intermedia two mutations
      were statistically prevalent: IVS1-6 T-->C (P < 0.001) and CD 6-A (P < 0.05). CD
      39 was statistically prevalent in beta-thalassaemia major patients (P < 0.01).
      The difference between the two groups was not statistically significant for all
      the other mutations. Five different genotypes were recorded among thalassaemia
      intermedia and 15 among beta-thalassaemia major patients. Twenty-five percent of
      the intermedia patients and 4.5% of the major patients had homozygosity for mild
      mutations (group I); 62.5% of the intermedia patients and 26.2% of the major
      patients had combinations of mild/severe mutations (group II). In addition,
      homozygosity or double heterozygosity for severe mutations (group III) was found
      in 12.5% of the intermedia patients and 69% of the major patients. Some genotypes
      were restricted to thalassaemia intermedia, including heterozygosity -87/IVS1-6
      and IVS1-6/CD 6-A. It is essential to understand the distribution and frequency
      of the relevant mutations in each population where beta-thalassaemias exist. This
      is of particular importance for genotype-phenotype correlation and for carrier
      detection, genetic counselling and prenatal diagnosis.

PMID- 11843885
TI  - Evaluation of a new screening test for sickle cell haemoglobin.
AB  - A new kit for screening for sickle cell haemoglobin (haemoglobin S) has been
      evaluated. The kit is based on the principle that cells containing haemoglobin S,
      which have been induced to sickle by exposure to a reducing agent in a phosphate
      buffer, do not pass through a gel contained in microtubules. In theory, they can
      thus be distinguished from cells that do not contain haemoglobin S. In practice,
      the kit was found to be insensitive and unreliable for the detection of
      haemoglobin S. Homozygosity and heterozygosity for haemoglobin S could not be
      reliably distinguished. Similarly, patients with haemoglobin S who had been
      transfused could not be distinguished reliably from those who had not been
      transfused. In conclusion, unless improved performance can be demonstrated, use
      of this kit cannot be recommended.

PMID- 11843886
TI  - Detection of hairy cell leukaemia in blood and bone marrow using multidimensional
      flow cytometry with CD45-PECy5 and SS gating.
AB  - CD45 and right angle light scatter (SS) gating are used commonly in clinical flow
      cytometry to differentiate cells of various lineages (Stelzer et al., 1993). We
      have used CD45-PECy5 (Clone J33) since 1998 and have noticed that malignant
      lymphoid cells such as hairy cells can form distinct populations. Previous
      studies indicate that hairy cells reside where normal monocytes are usually found
      in CD45/SS scatter plots (Wells et al., 1998). We studied six patients with hairy
      cell leukaemia (HCL) and found that hairy cells have a higher CD45 mean cell
      fluorescence than normal lymphocytes and monocytes. Two of the six patients
      presented with mild unexplained cytopenias, without the usual clinical,
      morphological and cytochemical findings. In both cases, CD45/SS gating of bone
      marrow cells showed a small population with strong expression of CD45. The
      presence of hairy cells was confirmed using a panel of monoclonal antibodies. In
      one patient with HCL variant, CD45 expression was indistinguishable from that of
      normal lymphocytes. We conclude that CD45-PECy5 (Clone J33) is useful for
      screening peripheral blood and bone marrow and for the detection of HCL without
      obvious morphological involvement.

PMID- 11843887
TI  - Survey of the use of whole blood in current blood transfusion practice.
AB  - Limited use of whole blood has continued despite a general move to blood
      component therapy in recent years. This paper describes the results of a
      questionnaire survey which was distributed to haematologists in charge of blood
      banks in England and North Wales to ascertain how much and for which indications
      whole blood was being requested. There was a 58% response rate. More than 90% of
      hospitals that responded had not requested whole blood during the last 12 months.
      Indications for the use of whole blood were primarily in paediatric practice,
      mostly for neonatal exchange transfusion or paediatric surgery (cardiac or
      craniofacial). Infrequent use in adult practice was for "major bleeding" when
      whole blood was available, and in cardiac surgery, when post-operative bleeding
      was unresponsive to standard replacement therapy. The evidence for the use of
      whole blood in preference to component therapy in the massive transfusion setting
      was reviewed, and no compelling evidence was found for its routine use for this
      indication. It is worth noting that, as currently supplied in the UK, "whole
      blood" is not strictly "whole" as the leucocyte-depletion process removes
      platelets.

PMID- 11843888
TI  - Placing the newborn on the maternal abdomen increases the volume of umbilical
      cord blood collected.
AB  - Haematopoietic stem cell transplantation is an important therapy for certain
      haematological and malignant disorders. Umbilical cord blood contains a high
      proportion of potentially transplantable haematopoietic progenitor cells.
      However, the use of cord blood stem cell transplantation is limited by the low
      number of stem cells obtainable from a single cord blood donor. The aim of our
      study was to investigate the possibility that procedures during delivery might
      influence the number of umbilical cord blood haematopoietic progenitor cells
      available for transplantation. We assessed the effects of upper and lower
      positions of the newborn infant on the yield of cord blood stem cells in 51
      vaginal deliveries. Neonates in the upper position group were placed by the
      midwife on the maternal abdomen immediately after birth, while those in the lower
      position group were placed on the delivery table, below the maternal introitus.
      The total volume of cord blood and the total number of CD34+ cells collected from
      babies in the upper position group were significantly higher than those from
      babies in the lower position group. There were no significant differences in cord
      blood haemoglobin levels and white blood cell counts between the two groups, nor
      were there any adverse effects in the newborn infants. The simple manoeuvre of
      placing the newborn on the maternal abdomen after delivery may thus increase the
      yield of transplantable haematopoietic progenitor cells in cord blood.

PMID- 11843889
TI  - Analysis of chimerism during the early period after allogeneic peripheral stem
      cell transplantation.
AB  - As there are few reports on early evaluation of chimerism, we assessed
      fluorescence short tandem repeats (STR) by polymerase chain reaction (PCR) assays
      to analyse donor and recipient characteristics at early time points after
      peripheral stem cell transplantation (PBSCT). Peripheral blood of 13 patients was
      analysed in 1- to 2-day intervals starting from the day of PBSCT. Donor and
      recipient allelic patterns were determined by a commercially available multiplex
      STR assay that simultaneously evaluates four or five gene loci. Mixed chimerism
      appeared in all patients during days 1-9 after transplantation and preceded
      haematologic engraftment for 3-12 days. Even patients without myeloablative
      conditioning therapy (n=4) revealed donor allelic patterns within 1-5 days. Nine
      patients changed during the following days to a complete donor allelic pattern
      and had an uncomplicated post-transplant disease course. Four patients did not
      consistently retain complete donor chimerism; two of them relapsed within the
      next 3 months, one died from septicemia within 7 days, and the fourth,
      transplanted for aplastic anaemia, is still in complete remission. Overall, STR
      analysis using a simple and comparatively cheap multiplex system permits the
      detection of chimerism very early after transplantation and may provide relevant
      information that correlates with the clinical follow-up.

PMID- 11843890
TI  - Haemoglobin Pierre-Benite--a high affinity variant associated with relative
      polycythaemia.
AB  - This is the second reported example of Hb Pierre--Benite (beta90 Glu-->Asp). This
      mutation is associated with increased oxygen affinity and polycythaemia. No
      instability was found and there was no charge shift detected by cellulose acetate
      electrophoresis at pH 8.3. The mutation was however, clearly indicated by
      electrospray ionization mass spectrometry (ESI MS), which showed an abnormal beta
      chain with a 14 Da decrease in mass. Blood volume studies documented a relative
      rather than a true polycythaemia and this finding has been reported in at least
      two other high affinity haemoglobin variants--Hb Heathrow and Hb Rahere. This
      finding led to delay in diagnosis because high oxygen affinity variants are
      conventionally considered to cause a true polycythaemia.

PMID- 11843891
TI  - Increased incidence of venous thrombosis in patients with shortened activated
      partial thromboplastin times and low ratios for activated protein C resistance.
AB  - A cohort of 69 hospital patients with shortened activated partial thromboplastin
      time (APTT) were prospectively identified and were further investigated for
      resistance to activated protein C (APC). This was quantified by APTT-based and
      Russel viper venom time (RVVT)-based methods. The prevalence of objectively
      confirmed venous thromboembolism (VTE) in this cohort was 19% (13/69). Of these
      69 patients, 28 also had low APC resistance ratios and the incidence of VTE among
      these patients (group 1) was 36% (10/28). This was significantly higher (P=0.003)
      than that in the remaining 41 patients (group 2) with shortened APTT and normal
      APC resistance (7%, 3/41). DNA analysis confirmed 13 of the group 1 patients were
      FV Leiden positive. The incidence of VTE in the FV Leiden group (group 1a, n=13)
      was 38% (5/13) and in the group whose abnormal resistance to APC was independent
      of FV Leiden (group 1b, n=15) was 33% (5/15). These results suggest that a
      shortened APTT, coexisting with a low APC resistance ratio, regardless of FV
      Leiden carriership status, is a marker for VTE. Increased resistance to the
      anticoagulant activity of APC is multifactorial as reflected by evidence of
      abnormal resistance differing in the two assays.

PMID- 11843892
TI  - Revised guideline on immunophenotyping in acute leukaemias and chronic
      lymphoproliferative disorders.

PMID- 11843893
TI  - Patterns of pseudo-reticulocytosis in malaria: fluorescent analysis with the Cell
      Dyn CD4000.
AB  - This study of Plasmodium falciparum malaria evaluated patterns of fluorescent
      reticulocyte measurements as determined with the Abbott Cell-Dyn CD4000. The
      parasitaemia of positive samples (n=180) ranged from 0.04% to 25.5%, with those
      (19/180) showing gametocytes having lower parasitaemia levels (mean 0.31%, median
      0.2%) compared to those that did not (mean 2.59%, median 0.8%). There was a
      reasonable association (R2=0.60) between parasitaemia level and CD4000
      reticulocyte percentages, although there was overall a small statistical bias
      towards higher parasitaemia estimates determined microscopically. Consistently
      high immature reticulocyte fraction (IRF) values of >0.5 were observed in cases
      with a parasitaemia exceeding 5%, while samples with lower parasitaemia levels
      showed more variable IRF values. Visual examination of CD4000 reticulocyte
      histograms revealed that 81/100 malaria-positive samples with an IRF above 0.5
      showed the presence of a fluorescent population 'spike' consistent with the
      staining of intracellular malaria parasites. Only three of the 80 malaria
      positive samples with an IRF below 0.5, and none of the 237 malaria-negative
      samples, showed this histogram pattern. These observations indicate that samples
      with malaria parasites give erroneously high CD4000 reticulocyte estimates that
      essentially comprise the sum total of true reticulocytes and parasite-infected
      red cells (pseudo-reticulocytes). This limitation is common to all automated
      reticulocyte procedures but recognizing the differences between homogenous
      staining parasitized red cells and heterogeneous staining reticulocytes has
      potential applications in monitoring parasitaemia levels both at patient
      presentation and during subsequent treatment.

PMID- 11843894
TI  - Liver function tests in sickle cell disease.
AB  - We investigated the prevalence of positive viral hepatitis titres in sickle cell
      disease (SCD) and the relationship of abnormal liver function tests (LFTs) to
      transfusions and ferritin levels. Charts from 141 patients with SCD were reviewed
      and recent laboratory data on serum ferritin, hepatitis serology, units of packed
      red blood cells transfused and LFTs were collected. Hepatitis B core antibodies
      were positive in 14% of patients (12/86) and Hepatitis C viral antibody titres
      were positive in 16.5% (15/91). There was a relationship of positive serologies
      to transfusion for hepatitis C virus (HCV), but not for hepatitis B virus (HBV).
      Hepatitis C antibody negative (HCVAb-) patients had fewer packed red blood cells
      (pRBC) transfused than Hepatitis C antibody positive (HCVAb+) (6.4 vs. 20.3,
      P=0.08). Patients with ferritins < 500 ng/ml compared to those with > 1000 ng/ml
      also showed a difference in units transfused (P < 0.003). Steady state LFTs, with
      the exception of alkaline phosphatase, had no relationship to serum ferritin or
      hepatitis serologies. Males were twice as likely to have positive serology as
      females but more females had elevated ferritin levels. Paired analysis of LFTs in
      steady state and crisis failed to demonstrate deterioration during crisis. We
      conclude that: (1) there is a relationship of positive Hepatitis C serology, but
      not Hepatitis B serology, to transfusion; (2) ferritin levels correlate with
      transfusion number but not with LFTs; (3) in our population, LFTs in SCD are
      usually normal and do not increase in vaso-occlusive crises.

PMID- 11843895
TI  - Activation of granulocytes in patients treated with chemotherapy.
AB  - It is well known that patients with granulocytopenia due to chemotherapy are
      susceptible to life-threatening infections. To determine whether or not
      granulocyte function is also impaired by chemotherapy, respiratory burst, CD11b
      and CD18 expression were analysed by flow cytometry in granulocytes from 10
      patients with haematological malignancies: before and after the commencement of
      high-dose chemotherapy and in the recovery phase. As a comparison, the same
      granulocytic functions were analysed in patients treated with low-dose
      hydroxyurea and in healthy volunteers. The granulocytes were activated by
      Staphylococcus aureus and Staphylococcus epidermidis. A decreased ability to
      mobilize CD18 in the recovery phase was seen, but the significance of this
      finding must be evaluated carefully owing to the small patient number.

PMID- 11843896
TI  - The diagnostic value of kappa/lambda ratios determined by flow cytometric
      analysis of biopsy specimens in B-cell lymphoma.
AB  - Flow cytometry (FC) is widely utilized in the diagnosis of lymphoma and the light
      chain ratio (LCR) is especially useful in the diagnosis of B-cell malignancy. In
      this study we analysed, retrospectively, the predictive value of the LCR in the
      diagnosis of B-cell lymphoma in 105 consecutive patients with persistent lymph
      node enlargement or extranodal masses who underwent biopsy. We used a receiver
      operating characteristic curve to establish a LCR threshold value of 2.0. The
      specificity, sensitivity, positive and negative predictive values were 92.3%,
      73.1%, 90% and 77%, respectively. We concluded that determination of LCR is a
      useful adjunct to pathological diagnosis.

PMID- 11843898
TI  - Audit of anticoagulant therapy and acute hospital admissions.
AB  - We conducted an audit on the contribution of failure of control of anticoagulant
      therapy to acute hospital admissions. Over a period of 3 months there were 1480
      acute admissions. One-hundred-and-twelve (7.6%) of these patients were on
      anticoagulant therapy. One-hundred-and-three of these 112 patients were
      evaluated, 74 patients had international normalized ratios (INRs) in the
      therapeutic range, of whom four (5.4%) bled from causes unlikely to be due
      directly to anticoagulant therapy. Twenty-nine patients were over-anticoagulated.
      Of these, 17 (59%) were admitted with bleeding symptoms, which may have been a
      consequence of high INR, while one had a very high INR but no bleeding. Eleven
      more patients were admitted for reasons unrelated to anticoagulant therapy but
      were found to have over-therapeutic INRs, which may have influenced their
      subsequent hospital management. The only clear difference between the bleeding
      and nonbleeding groups was age. Reasons for over-anticoagulation were poor
      patient compliance in 31%, influence of other medications in 17, congestive heart
      failure in 28%, and unknown in 24%. In conclusion, 22/1480 hospital admissions
      (1.5%) were due to warfarin complications and 16/21 bleeding patients had INRs >
      4.5. These are admissions that could potentially be avoided with better
      anticoagulation control.

PMID- 11843897
TI  - Fluctuations in plasma macrophage colony-stimulating factor levels during
      autologous peripheral blood stem cell transplantation for haematologic diseases.
AB  - Plasma macrophage colony-stimulating factor (M-CSF) levels were measured in 13
      haematologic patients treated with autologous peripheral blood stem cell
      transplantation (PBSCT). Six of the patients showed an increase in M-CSF peak
      levels (>3000 pg/ml) during the conditioning and stem cell infusion period. The
      peak levels of M-CSF in this phase correlated with thrombomodulin levels,
      indicating the endothelial origin of plasma M-CSF. However, the M-CSF levels were
      not influenced by TNFalpha. More patients with high M-CSF levels (>5000 pg/ml)
      suffered from organ failure than those with lower M-CSF levels. These results
      suggest that high M-CSF levels may correlate with cellular or organ damage in
      patients treated with PBSCT.

PMID- 11843900
TI  - Idiopathic myelofibrosis with extramedullary haemopoiesis involving the urinary
      bladder in a Chinese lady.
AB  - Extramedullary haemopoiesis (EMH) associated with idiopathic myelofibrosis most
      commonly involves the reticuloendothelial organs, such as the spleen and liver,
      although ectopic haemopoietic tissue has also been described rarely in the lymph
      nodes, skin, gastrointestinal tract, pleura, peritoneum, central nervous system,
      and genital and urinary tracts. We report on a 54-year-old Chinese lady with a
      long history of idiopathic myelofibrosis who presented with gross haematuria and
      left hydronephrosis due to EMH in the bladder trigone. Cystoscopic examination
      revealed a sessile necrotic papillary growth at the trigone, obstructing the left
      ureteric orifice. Transurethral resection of the bladder tumour was performed,
      and microscopic examination of the tumour chips demonstrated atypical
      megakaryocytes, immature granulocytes and normoblasts, confirming the presence of
      EMH. The residual bladder tumour responded well to low dose radiotherapy, with
      subsequent disappearance of haematuria and normalization of ultrasonogram
      findings.

PMID- 11843899
TI  - Quantification of foetomaternal haemorrhage. An analysis of two cytometric
      techniques and a semiquantitative gel agglutination test.
AB  - Traditional tests to screen for foetomaternal haemorrhage are time-consuming and
      difficult to perform. The Kleihauer test is widely used but difficult to
      standardize. We evaluated three techniques for quantifying foetomaternal
      haemorrhage: a semiquantitative gel agglutination test and two flow cytometric
      techniques. The gel agglutination test is based on the consumption of anti-D
      reagent by D+ cells, analysing the reaction of the supernatant against indicator
      cells in a Coombs-gel card. In the two colour direct immunofluorescent technique,
      the sample is incubated with Per-CP labelled anti CD45 antibody, fixed with
      glutaraldehyde and permeabilized by exposure to Triton X-100. An aliquot is
      stained with an antibody to foetal haemoglobin, conjugated with fluorescein
      isothiocyanate or phycoerythrin. The indirect immunofluorescent technique is
      based on the labelling of Rh (D) antigen with an anti D reagent, followed by the
      addition of an anti IgG antibody conjugated with phycoerythrin. Foetomaternal
      haemorrhage was not detected in 75 of the 85 samples analysed by the direct
      immunofluorescent technique. In the remaining 10 samples, the volume was very
      low. Thirty-five samples with Rh (D) antigen incompatibility were analysed in
      parallel by the indirect immunofluorescent technique and in 15 of the 35 samples,
      the gel agglutination technique was also carried out. The three techniques gave
      similar results. The gel agglutination test can be used to screen for
      foetomaternal haemorrhage, while greater volumes should be quantified by flow
      cytometric techniques.

PMID- 11843901
TI  - Multiple thrombophilic factors in a patient with Budd-Chiari syndrome.
AB  - Myeloproliferative disorders are the main cause of Budd-Chiari syndrome in
      western countries. Inherited or acquired thrombophilic factors have also been
      implicated. A novel mutation of the prothrombin gene (G-->A20210) has only been
      described in a few cases of Budd-Chiari syndrome so far. Venous thrombosis is
      often the result of multiple concomitant thrombophilic factors. We report the
      case of a patient with essential thrombocythemia and Budd-Chiari syndrome in
      which heterozygosity for both factor V Leiden and the mutation G20210A of the
      prothrombin gene were identified.

PMID- 11843902
TI  - Haematocrit measurement and antidoping policies.

PMID- 11843903
TI  - EDTA-dependent leukoagglutination.

PMID- 11843905
TI  - Prevention and management of infections in patients without a spleen.
AB  - Patients who lack a functioning spleen become vulnerable to sepsis caused by
      bacteria and, occasionally, protozoa. The risk is higher in children and in those
      who have had immunosuppressive treatment, and the risk remains lifelong.
      Overwhelming post-splenectomy infection (OPSI) occurs at an estimated incidence
      of 0.23-0.42% per year, with a lifetime risk of 5%. Episodes of OPSI are
      emergencies, requiring immediate parental antibiotics and intensive care;
      intravenous immunoglobulins may be useful. OPSI carries a mortality of 38-69%.
      Streptococcus pneumoniae is the commonest infecting organism, accounting for 50
      90% of isolates from blood cultures in reported series; it is particularly common
      in children with sickle cell disease. Less commonly, the infecting organisms are
      other bacteria, Babesia or Ehrlichia. OPSI may be, to some extent, preventable by
      several interventions. These are surgical conservation of the spleen;
      immunization against S. pneumoniae, Haemophilus influenzae type b, and Neisseria
      meningitidis; prophylactic antibiotics; stand-by antibiotics; patient information
      sheets; and a medical alert bracelet. Asplenic patients living in malaria-endemic
      areas require optimal prophylaxis. The initial step in prevention of OPSI is the
      creation of an asplenia register, as many patients are not covered by these
      simple measures.

PMID- 11843906
TI  - Evidence for a true post-beta-lactamase-inhibitor effect of clavulanic acid
      against Klebsiella pneumoniae and Haemophilus influenzae.
AB  - OBJECTIVE: The purpose of this study was to investigate and characterize in vitro
      the post-beta-lactamase inhibitor effect (PLIE) of clavulanic acid against two
      beta-lactamase-producing species of bacteria. METHODS: The PLIE was investigated
      against one strain of Klebsiella pneumoniae and one strain of Haemophilus
      influenzae. A stationary-phase inoculum of about 107 colony-forming units per mL
      of each bacterium was pre-exposed for 2 h to clavulanic acid, either alone or in
      combination with amoxicillin at various concentrations. After pre-exposure, the
      dilution required to remove the beta-lactamase inhibitor was 1:100 or 1:1000
      according to the bacterial species and their susceptibilities to clavulanic acid.
      Bacteria were counted hourly after drug removal, on solid agar medium. RESULTS:
      Control cultures exposed to amoxicillin alone after dilution, showed a delay in
      growth, which may be inherent to the time required to synthesize sufficient beta
      lactamase after the dilution steps. Control experiments clearly distinguished the
      post-antibiotic effect and the growth delay from the PLIE. CONCLUSION: The PLIE
      could be one of several factors explaining why beta-lactam/beta-lactamase
      inhibitor combinations remain effective throughout the dosing interval, even if a
      few hours after in vivo administration, serum concentrations of beta-lactamase
      inhibitor fall below levels that are active in vitro.

PMID- 11843907
TI  - Epidemiology and resource utilization for patients hospitalized for lower
      respiratory tract infection.
AB  - OBJECTIVES: To determine referral rates, patient characteristics, and resource
      utilization for patients admitted to hospital with community-acquired lower
      respiratory tract infections (LRTI). METHODS: Six hundred and thirteen patients,
      accounting for 704 LRTI episodes, were included in the study, if the referral
      diagnosis was LRTI and if both signs and symptoms on admission and patient
      management were consistent with this diagnosis. Patient records were abstracted
      to collect information on co-morbidities, patient demographics, resource
      utilization, episode outcome, pharmacy prescribing and diagnostic service
      utilization. RESULTS: Annual hospital admissions for LRTI ranged from 15 per 10
      000 population in the age range 16-40 years to over 300 per 10 000 in the
      population aged >79 years, with a population average of 62.3 per 10 000. Less
      than 37% of admissions were for community-acquired pneumonia and the majority of
      episodes were in patients with pre-existing respiratory disease (41.2%). Marital
      status, gender, diabetic status, type of infection and number of days in hospital
      within the past year were all significantly associated with changes in mean
      length of stay. CONCLUSIONS: Hospital episodes of LRTI are seen predominantly in
      the over-60 age group, which account for almost 90% of bed day utilization, yet
      represent only 27% of the adult population. Referral of patients to hospital with
      LRTI represents a major resource implication for secondary health-care provision.

PMID- 11843908
TI  - Antimicrobial susceptibilities of clinical isolates of Haemophilus influenzae and
      Moraxella catarrhalis collected during 1999-2000 from 13 countries.
AB  - OBJECTIVE: To determine antimicrobial activity against Haemophilus influenzae and
      Moraxella catarrhalis. METHODS: A central laboratory performed NCCLS
      susceptibility testing for all isolates and beta-lactamase and capsular serotype
      determinations for H. influenzae. RESULTS: A total of 2712 H. influenzae and 1079
      M. catarrhalis were collected. H. influenzae susceptibilities were >90% for
      amoxicillin/clavulanate, cefaclor, loracarbef, cefprozil, cefuroxime,
      ciprofloxacin, azithromycin and clarithromycin and were <80% for
      trimethoprim/sulfamethoxazole and ampicillin. 19.3% were beta-lactamase positive.
      The most common serotype was type-b (5.6%); 86.1% were nontypeable. M.
      catarrhalis had MIC90 within therapeutic range for all antimicrobials except
      ampicillin. CONCLUSION: The conclusion of the study is that antimicrobials,
      except ampicillin and trimethoprim/sulfamethoxazole, remain good empiric choices
      against H. influenzae and M. catarrhalis.

PMID- 11843909
TI  - Overall trends in CD4 counts and plasma viremia in an urban clinic since the
      introduction of highly active antiretroviral therapies.
AB  - OBJECTIVE: To assess whether the benefit of highly active antiretroviral
      therapies (HAART) is continuing, a longitudinal retrospective study of CD4 counts
      and viral load (VL) in a large group of human immunodeficiency virus (HIV)
      infected subjects was undertaken in Madrid. METHODS: Consecutive plasma VL values
      and CD4+ T-lymphocyte counts were collected during a 3-month period yearly from
      1996 to 2000 in one HIV/acquired immune deficiency syndrome (AIDS) reference
      institution, where currently around 1500 HIV-infected individuals are on regular
      follow-up. RESULTS: VL values and CD4+ counts were collected at each time-point
      from an average of 375 and 391 patients, respectively. The proportion of subjects
      receiving HAART among those on any kind of antiretroviral treatment increased
      between 1996 (61%) and 2000 (95.1%) (P < 0.01). The number of subjects with
      undetectable VL (<500 HIV-RNA copies/mL) increased from 12% in 1996 to 64% in
      2000 (P < 0.01). Accordingly, the proportion of individuals with CD4+ counts >500
      cells/microL increased from 16% in 1997 to 54% in 2000 (P < 0.01). Notably, the
      number of subjects with VL values >10 000 copies/mL has declined over time, and
      currently represents only 17% of the population. Despite this favorable trend,
      the proportion of subjects with low CD4+ counts (<200 cells/microL) seems to have
      reached a plateau, in the range of 10%. CONCLUSIONS: A dramatic virological and
      immunological benefit has followed the introduction of HAART in HIV-infected
      patients since 1996. This favorable trend seems to be maintained over time,
      despite the negative impact of drug-related toxicity and/or adherence issues.
      However, a subgroup of subjects seems to persist with low CD4 counts despite
      having good virological control. They should be managed with alternative
      treatment strategies, including immune stimulatory agents.

PMID- 11843910
TI  - The prevalence of antibiotic resistance in bacterial respiratory pathogens from
      Norway is low.
AB  - OBJECTIVES: To determine the degree of bacterial susceptibility to the most
      commonly used drugs for respiratory infections in Norway, and to find if
      bacterial resistance is emerging. METHODS: Clinical isolates of Streptococcus
      pneumoniae, Haemophilus influenzae and group A streptococci from respiratory
      tract specimens and from the eye were collected from different parts of Norway
      during two study periods. During the first period (1993-1994), three
      laboratories, covering 15% of the Norwegian population, participated. During the
      second study period in 1997, five laboratories, covering 27% of the population,
      collected respiratory isolates. In total, 494 isolates of S. pneumoniae, 696
      isolates of H. influenzae and 694 isolates of group A streptococci were included
      in the study. The study population comprised children and adults attending
      hospital and general practice. Bacterial susceptibility was determined by the E
      test, and breakpoints were according to the National Committee for Clinical
      Laboratory Standards (NCCLS). RESULTS: The prevalence of bacterial resistance was
      low, and we observed no significant increase in bacterial resistance between the
      two study periods. In 1997, only 0.6% of pneumococci had decreased susceptibility
      to penicillin, 1.6% of group A streptococci were resistant to erythromycin, and
      6.7% of all isolates of H. influenzae produced beta-lactamase. CONCLUSIONS: The
      prevalence of antibiotic resistance in respiratory pathogens in Norway is low.

PMID- 11843911
TI  - Detection of human papillomavirus (HPV) genotypes in cervico-vaginal scrapes of
      women with normal and abnormal cytology.
AB  - BACKGROUND: Certain types of human papillomavirus (HPV) are associated with
      cervical intraepithelial neoplasia (CIN) and invasive cervical carcinoma. The
      study addressed the expression and detection of HPV genotypes in cervical and
      vaginal specimens of women with normal and abnormal cytology by polymerase chain
      reaction (PCR), each woman serving as her own control. METHODS: Study
      participants (127) were subgrouped into CIN-positive and CIN-negative, based on
      cytology screening, and endocervical and vaginal scrapes were collected by a
      gynecologist and placed immediately in saline. HPV DNA was assessed by PCR, and
      HPV genotypes were determined by hybridization of PCR products with type-specific
      biotinylated probes. RESULTS: Of the 127 participants, 55 tested positive and 72
      tested negative for HPV DNA. While there was no difference between the two groups
      with regards to age or to number of pregnancies, higher numbers of smokers and of
      women with multiple sexual partners and abnormal cytology were seen in the HPV
      positive group (P < 0.001). HPV DNA was detected in the vaginal scrapes of all
      HPV-positive, but in none of the HPV-negative women (sensitivity and specificity
      = 1.0). Furthermore, the HPV genotype was the same in vaginal and endocervical
      specimens in all the HPV-positive women. CONCLUSION: HPV detection by PCR, using
      endocervical or vaginal sampling, is a sensitive and highly specific test for the
      identification of HPV infection, in particular in women with cytomorphologically
      normal cervices.

PMID- 11843912
TI  - Clinical microbiological case: large endocardial vegetation in an Italian woman.

PMID- 11843913
TI  - Clinical microbiological case: penile ulcer and lung infiltrates in a leukemic
      patient.

PMID- 11843914
TI  - An unusual case of anti-Borrelia burgdorferi immunoglobulin G seroconversion
      caused by administration of intravenous gammaglobulins.
AB  - Administration of gammaglobulins to individuals without specific anti-Borrelia
      burgdorferi antibodies may lead to immunoglobulin G (IgG) conversion as detected
      by enzyme-linked immunosorbent assay (ELISA). In some cases however,
      complementary techniques such as Western blot or avidity will be of prime
      importance in distinguishing the start of an infection from the passive
      immunization induced by the gammaglobulins. In all cases, the key element before
      reaching conclusions in relation to any of these investigations remains the
      confrontation between the clinical context and the biological findings. This is
      the scenario that has been followed in our observation.

PMID- 11843915
TI  - In vitro susceptibility of Mycobacterium tuberculosis to fusidic acid.
AB  - The aim of this study was to determine the in vitro susceptibility of 170
      clinical isolates of Mycobacterium tuberculosis to fusidic acid using a
      proportion dilution method. Nineteen isolates were resistant to at least one
      first-line anti-tuberculosis drug. A total of 1.8% of the isolates were resistant
      to fusidic acid. Fusidic acid should be evaluated clinically as a potential
      supplementary drug for the treatment of infections due to multidrug-resistant
      strains of M. tuberculosis.

PMID- 11843916
TI  - Activity of telithromycin against 26 quinolone-resistant pneumococci with known
      quinolone-resistance mechanisms.
AB  - NCCLS agar dilution was used to test activity of telithromycin compared to
      clarithromycin, penicillin G, ciprofloxacin, levofloxacin, sparfloxacin and
      moxifloxacin against 26 pneumococci with defined quinolone resistance (type II
      topoisomerase and efflux) mechanisms. Thirteen strains were penicillin
      susceptible, six intermediate and seven resistant. Clarithromycin resistance (mef
      and/or erm) was seen in eight strains. Ciprofloxacin MICs (mg/L) were 8-64
      compared to 1-32 (levofloxacin), 0.5 . or = 32 (sparfloxacin) and 0.125-4
      (moxifloxacin). Telithromycin MIC50 and MIC90 values (mg/L) were 0.016 and 0.25,
      with only one strain having an MIC of 2 mg/L.

PMID- 11843917
TI  - Pseudomonas aeruginosa: antibiotic susceptibility and genotypic characterization
      of strains isolated in the intensive care unit.
AB  - A prospective study was carried out to assess the incidence and the local
      antibiotic susceptibility of Pseudomonas aeruginosa in intensive care units
      (ICUs) and to characterize cross-transmission by using pulsed-field gel
      electrophoresis as an epidemiologic tool. For this purpose, we screened
      surveillance cultures and routine clinical cultures from patients admitted to two
      adult ICUs during a 2-year period. Antibiotic susceptibility was determined by a
      disk diffusion method. The overall incidence of P. aeruginosa was 19.1 cases per
      100 patients. Our findings concerning the antibiotic resistance of clinical
      isolates were concordant with those of other studies. Genotyping revealed that
      approximately 53.5% of P. aeruginosa colonization was acquired via cross
      transmission; the other cases probably originated from endogenous sources. Cross
      colonization seems to make a large contribution to the spread of P. aeruginosa in
      ICUs.

PMID- 11843918
TI  - Rapid method of extraction and analysis of extended-spectrum beta-lactamases from
      clinical strains of Klebsiella pneumoniae.
AB  - The extraction of periplasmic beta-lactamases from Gram-negative bacilli is a
      necessary preliminary step to analytical isoelectric focusing. Previously
      described methods are time-consuming and require large amounts of broth. We
      describe a lysozyme-based method which needs just 5 mL broth and requires less
      than 24 h to perform. The method was reproducible in extracting beta-lactamases
      from reference strains containing known beta-lactamases. We applied the method to
      a collection of more than 70 extended-spectrum beta-lactamase-producing isolates
      from a multinational study of bacteremic isolates of Klebsiella pneumoniae.
      Further studies are being undertaken to assess the method's applicability to
      other bacterial species.

PMID- 11843919
TI  - Has the Calman Report been understood and implemented correctly?

PMID- 11843920
TI  - The history, aetiology and epidemiology of laryngeal carcinoma.

PMID- 11843921
TI  - A report of 50 patients with carcinoma of the hypopharynx treated by total
      pharyngolaryngo-oesophagectomy repaired by gastric transposition.
AB  - Extensive carcinoma of the hypopharynx requires aggressive surgery, which can
      lead to loss of function and a high morbidity and mortality. This paper reports
      50 patients with carcinoma of the hypopharynx treated with total pharyngolaryngo
      oesophagectomy and gastric transposition. Thirty-two patients had primary surgery
      and 18 had salvage surgery for recurrence following radiotherapy. Two technical
      modifications to the standard procedure that have evolved during this period are
      the use of a diverticuloscope for dissection of the middle third of the
      oesophagus and the routine insertion of chest drains peroperatively.
      Complications were relatively unusual in the primary surgery group, but were a
      problem in those patients undergoing salvage surgery. Stenosis did not tend to
      occur with gastric transposition repair, but three patients had delayed gastric
      emptying with prolonged hospital stays. The tumour-specific actuarial survival at
      4 years was 39% and the observed survival was 25%. Pharyngolaryngo-oesophagectomy
      and gastric transposition is becoming safer owing to increased multidisciplinary
      experience in this form of surgery. Survival is improved with the use of
      postoperative radiotherapy in patients undergoing primary surgery.

PMID- 11843922
TI  - Intracranial complications of acute frontal sinusitis.
AB  - Despite advances in the diagnosis and treatment of acute frontal sinusitis, there
      is still significant occurrence of intracranial complications. Urgent surgical
      evacuation of any intracranial collection is required; however, the surgical
      management of the associated sinusitis remains controversial. Ten patients
      presented to this department over a 12-month period with subdural empyema
      secondary to acute frontal sinusitis. Four patients had a coexisting Pott's puffy
      tumour and one patient had a periorbital abscess. Each patient was managed using
      a multidisciplinary approach. A frontal sinus trephine/drain +/- antral washout
      was performed at the same time as craniotomy with evacuation of the empyema. With
      this approach only two patients suffered long-term morbidity in our series, in
      the form of persistent neurological or cognitive deficit. No patient required a
      definitive sinus procedure. This study emphasizes the need for the early
      assessment and intervention of patients with an intracranial complication
      secondary to acute frontal sinusitis. Further assessment of the underlying sinus
      disease is indicated during outpatient follow up after the acute episode.

PMID- 11843923
TI  - How well do parents recognize the difference between tonsillitis and other sore
      throats?
AB  - Little evidence exists from randomized controlled trials to support the role of
      tonsillectomy in children with recurrent tonsillitis. Despite this, parents
      report a great change for the better in their children following the operation.
      Previous trials vary in their inclusion criteria, both in terms of the definition
      of tonsillitis and in the frequency of sore throats required before entry into
      the study is permitted. The aims of this study are to define tonsillitis from the
      perspective of parents whose children are awaiting tonsillectomy for recurrent
      sore throats, and to determine whether such parents have a better understanding
      of the difference between tonsillitis and other sore throats than parents of
      children from a normal population control group. These aims demonstrate whether
      parents who request tonsillectomy for their children do so on the basis of a
      recognized clinical problem. We report that parents can clearly identify a sore
      throat illness that they call tonsillitis and which is differentiated from other
      sore throats by different symptom complexes. The parental history is important in
      the assessment of a child prior to tonsillectomy. The views of parents whose
      children have recurrent tonsillitis must be further investigated if the
      difference between randomised controlled trial results and parents' opinions
      regarding the benefit of tonsillectomy is to be understood.

PMID- 11843924
TI  - A prospective, single-blind, randomized controlled trial of antiseptic cream for
      recurrent epistaxis in childhood.
AB  - Epistaxis is common in children. Trials show antiseptic cream is as effective as
      cautery, but it is not known whether either is better than no treatment. We
      wished to know the efficacy of cream in children with recurrent epistaxis. The
      design was a single-blind, prospective, randomized controlled trial set in the
      Otolaryngology clinic in a children's hospital. The participants were 103
      children referred by their general practitioner for recurrent epistaxis. Excluded
      were those with suspected tumours, bleeding disorders or allergies to
      constituents of the cream. Referral letters were randomized to treatment and no
      treatment groups. Treatment was antiseptic cream to the nose twice daily for 4
      weeks, which was prescribed by the general practitioner before clinic attendance.
      All children were given an appointment for 8 weeks after randomization. The main
      outcome measures were the proportion of children in each group with no epistaxis
      in the 4 weeks preceding clinic review. Complete data were available for 88 (85%)
      of the children. Of the treatment group, 26/47 (55%) had no epistaxis in the 4
      weeks before the clinic appointment. Of the controls, 12/41 (29%) had no
      epistaxis over the 4 weeks. This is a relative risk reduction of 47% for
      persistent bleeding (95% CI 9-69%) and an absolute risk reduction of 26% (95% CI
      12-40%), giving a number needed to treat of 3.8 (95% CI 2.5-8.5). We conclude
      that antiseptic cream is an effective treatment for recurrent epistaxis in
      children.

PMID- 11843925
TI  - Expression of type IV collagen and matrix metalloproteinase-2 (type IV
      collagenase) in relation to nodal status in laryngeal cancer.
AB  - Laryngeal carcinoma has a lower incidence of neck metastases than other malignant
      carcinomas of the head and neck region. However, some cases are very aggressive,
      showing neck metastases even in the early stages. In this study the expression of
      collagen IV and type IV collagenase (MMP-2) were examined immunohistologically in
      50 patients with laryngeal carcinomas, and the results were compared with the
      incidence of neck metastases and other clinicopathological factors. The
      correlation between collagen IV expression and the existence of nodal metastases
      was statistically significant (P < 0.001). There was also significant correlation
      between collagen IV expression and the histological grading of the tumour. There
      was a tendency for samples with continuous collagen IV staining to have no matrix
      metalloproteinase-2 (MMP-2) immunoreactivity. No significant correlation was seen
      between MMP-2 protein expression and clinicopathological parameters although the
      correlation between MMP-2 and existence of nodal metastases was statistically
      borderline (P = 0.07). Multivariate analysis of the clinicopathological factors
      that may have an influence on the nodal status in laryngeal cancer revealed that,
      apart from T stage, collagen IV pattern in the basement membrane surrounding
      nests of carcinoma is an important prognostic factor.

PMID- 11843926
TI  - Results of stapes surgery on patients with osteogenesis imperfecta.
AB  - Osteogenesis imperfecta (OI) is a heterogeneous group of connective tissue
      disorders. The classic triad of blue sclerae, spontaneous fractures and hearing
      loss is known as the Van der Hoeve and De Kleyn syndrome. Between 1989 and 2000,
      six patients with OI presented with conductive hearing loss. Five of them
      proceeded to stapedotomy. All the patients who had surgery had significant
      hearing gain. None of the patients had any complications. This study presents a
      higher incidence of spontaneous fractured crura as the cause of the conductive
      hearing loss than previously reported, and that the presence of a fractured crura
      with mobile footplate can be anticipated by the presence of a large conductive
      hearing loss. The pre- and postoperative results are presented and support the
      view that stapes surgery in OI can have encouraging results, provided the
      operator anticipates the possibility of a fractured crura and a mobile footplate.

PMID- 11843927
TI  - Hereditary cochleovestibular dysfunction due to a COCH gene mutation (DFNA9): a
      follow-up study of a family.
AB  - Cochleovestibular impairment was evaluated, in relation to age, in a longitudinal
      follow-up study on a Dutch family with a DFNA9 trait caused by a Pro51Ser
      mutation in the COCH gene on chromosome 14q12-q13. Fourteen cases were genotyped.
      The onset age of progressive impairment reported by the mutation carriers was
      between age 35 and 45 years. Pure-tone thresholds deteriorated by about 2-7 dB
      per year (mean 3.8 dB per year) in a variable, often asymmetrical, fashion. One
      mutation carrier developed recurrent episodes of vertigo accompanied by nausea
      and vomiting, resembling Meniere's disease. Two others developed special
      susceptibility for motion sickness and appeared to have a hyperactive vestibulo
      ocular reflex. More advanced stages of vestibular impairment, i.e. vestibular
      hyporeflexia and complete vestibular areflexia, were eventually found in a number
      of cases. DFNA9/COCH should be considered as a possible cause in patients
      developing combined progressive cochlear and vestibular impairment, or suspected
      hereditary Meniere-like disease, from around middle age.

PMID- 11843928
TI  - Is the incidence of tonsillectomy influenced by the family medical or social
      history?
AB  - Previous reports have suggested that the incidence of tonsillectomy, and/or
      tonsillitis in children, is influenced by factors such as parental smoking,
      maternal health and previous parental tonsillectomy. The reports have considered
      single factors and have not considered the possible confounding effect of the
      factors upon one another. Previous studies have not investigated the influence of
      social class. This paper uses the background of a large case-control trial of
      children awaiting tonsillectomy for recurrent tonsillitis, and a normal control
      group to study the influence of parental smoking, parental surgical history,
      parental tonsillectomy, family atopy and social class upon the reported incidence
      of sore throats and tonsillitis. A multivariate analysis is used. The paper shows
      that parental smoking, previous parental surgery and social class have no effect
      upon the number of sore throat episodes. A history of parental tonsillectomy and
      a family history of atopy are both significant predictive factors for the number
      of reported sore throats and episodes of tonsillitis in children.

PMID- 11843929
TI  - The effect of inferior turbinate hypertrophy on nasal spray distribution to the
      middle meatus.
AB  - The distribution of topical nasal sprays is suboptimal, the main obstruction to
      adequate delivery in normal volunteers being the nasal valve. We aimed to test
      the hypothesis that, in patients with rhino-sinusitis, hypertrophy of the
      inferior turbinate also limits the distribution of administered drug to the
      middle meatus. We modelled the effect of inferior turbinate hypertrophy and
      reduction by effecting congestion (by ipsilateral isometric exercise) and
      decongestion (topical oxymetazoline) in normal volunteers. The method chosen to
      estimate drug delivery to the middle meatus used endoscopic photography after the
      administration of dyed aqueous spray. A randomized cross-over study design was
      used and 20 nasal cavities were studied. The congestion/decongestion manoeuvres
      significantly altered nasal airflow, as measured by peak inspiratory nasal flow
      (P < 0.001). Congestion diminished significantly drug delivery to the middle
      meatus, as compared with decongestion (P = 0.026). This may support a clinical
      role for inferior turbinate reduction to improve the efficacy of topical nasal
      therapy, as well as improving nasal airflow.

PMID- 11843930
TI  - Matrix metalloproteinases 2 and 9 in otitis media with effusion.
AB  - A qualitative and quantitative study of the presence of matrix metalloproteinase
      2 (MMP 2) and matrix metalloproteinase 9 (MMP 9), in the effusions of otitis
      media with effusion (OME), was performed. The activity of the above enzymes was
      compared in thick and thin effusions, and concentrations compared in samples from
      children with one, two, three and four sets of ventilation tubes. The activity of
      both MMP 2 and MMP 9 was higher in thick than thin effusions, P = 0.07 and P =
      0.04, respectively. The concentrations of MMP 9 did not vary with the number of
      tube insertions but those of MMP 2 did (ANOVA P < 0.05). MMPs may be involved in
      tympanic membrane damage and prognosis of OME.

PMID- 11843931
TI  - One-stop neck lump clinic: phase 2 of audit. How are we doing?
AB  - Regular monitoring and audit of a service are integral to ensuring maintenance of
      efficiency and standards. This is particularly important where the quality of the
      service is operator dependent, as is the case in the clinical diagnosis of neck
      lumps and fine needle aspiration cytology. The one-stop neck lump clinic has now
      been running in the department for more than 20 months. A previous article
      described the results of the first phase audit carried out at 6 months and had
      identified a waiting time to be seen that was longer than that recommended by the
      British Association of Otorhinolaryngologists, Head and Neck Surgeons. Measures
      were implemented to reduce this waiting time and a second audit was carried out
      after another 10 months with the aims of assessing if modification of the means
      of referral reduces waiting time and if the outcomes of clinical performance in
      phase 1 could be maintained or improved. We discuss the results of phase 2 in the
      audit spiral.

PMID- 11843932
TI  - The expression of vascular endothelial growth factor (VEGF) and VEGF-C in early
      laryngeal cancer: relationship with radioresistance.
AB  - Angiogenesis is essential for tumour growth and invasion. Vascular endothelial
      growth factor (VEGF) is a prime mediator of tumour angiogenesis. VEGF-C is a
      closely related protein that effects lymphatic endothelial cells and may be
      important in the process of lymphatic metastasis. The purpose of this study was
      to evaluate the expression of these cytokines in patients with T1 and T2a
      glottic, squamous cell carcinoma, in comparison with normal epithelial control
      tissue, to ascertain any association with radioresistance. Twenty-two tumours
      treated by radiotherapy (13 radiosensitive, nine radioresistant) and seven normal
      control tissues were studied. The minimum follow-up was 2 years after
      radiotherapy. Expression of VEGF and VEGF-C was evaluated by immunohistochemistry
      of formalin-fixed, paraffin-embedded biopsy specimens. Analysis was carried out
      using a quantitative computer image analyser. Both VEGF and VEGF-C were
      detectable in tumour and normal control specimens. There was increased expression
      in tumour specimens of both VEGF (P = 0.03) and VEGF-C (P < 0.001). In addition,
      the expression of VEGF-C was associated with tumours of higher histological grade
      (P = 0.021). There was, however, no difference in VEGF and VEGF-C expression
      between radioresistant and radiosensitive tumours. The expression of VEGF and
      VEGF-C is increased in early laryngeal squamous cell carcinoma (SCC). However,
      measuring the expression of these proteins cannot predict radioresistance in this
      tumour group.

PMID- 11843933
TI  - Helicobacter pylori and tonsillectomy.
AB  - Tonsillar tissue is a component of mucosa-associated lymphoid tissue (MALT),
      which has evolved to protect vulnerable mucosal surfaces. Helicobacter pylori,
      implicated as an aetiological factor in duodenal ulcers and gastritis, induces
      the appearance of lymphoid aggregates (MALT) in the stomach. This organism is
      cytotoxic via a nitric oxide synthase cascade. The possibility that tonsillar
      tissue processes Helicobacter pylori or that Helicobacter pylori can colonize the
      palatine tonsils is explored. The study design was that of a prospective study.
      We determined if Helicobacter pylori (i) forms part of the normal
      microenvironment of the tonsil, (ii) plays a role in the pathogenesis of
      tonsillitis and (iii) is associated with increased expression of inducible nitric
      oxide synthase (iNOS) in macrophages of the tonsil. Serology for Helicobacter
      pylori was performed on 50 patients undergoing tonsillectomy. Tonsillar specimens
      were monitored for urease activity by CLO test (a sealed plastic slide holding an
      agar gel, which contains urea and detects the urease enzyme of Helicobacter
      pylori), and immunocytochemically probed for Helicobacter pylori and iNOS
      expression. The mean age of this patient group was 17.2 years (3-36 years).
      Fourteen (28%) were sero-positive for Helicobacter pylori but no evidence of this
      pathogen was found in any tonsillar specimen. The number of macrophages staining
      for iNOS, per field, under a magnification of x40, was increased in sero-positive
      patients (13.3 +/- 1.3 versus 9.9 +/- 0.7; P = 0.01). Helicobacter pylori does
      not appear to colonize the tonsil. We believe that Helicobacter pylori primes the
      tonsils by inducing macrophage iNOS expression. The higher expression in sero
      positive patients is a reflection of a pro-inflammatory reaction to Helicobacter
      pylori that is both local and systemic.

PMID- 11843934
TI  - Nasal polyposis and facial pain.
AB  - A cohort of 973 patients with symptoms of rhinosinusitis and/or facial pain was
      followed up for a mean of 2 years 2 months and, within this, was a group of 220
      with nasal polyps. Only 39 (18%) had pain or pressure as a symptom. Out of the
      220 with nasal polyps, 190 had polyps without any purulent secretions and, of
      these, only 5 (2.6%) had pain attributable to their paranasal sinus disease. Ten
      out of the 15 with pain and polyps without pus were found to have pain as a
      result of neurological or medical cause after endoscopic sinus surgery and a
      trial of medical nasal treatment and, where necessary, drugs to treat
      neurological conditions. Thirty patients (13.6%) had nasal polyposis and purulent
      secretions, and, within this subgroup, 24 (79%) had pain as well. Of the 24 with
      pain and purulent secretions, 19 (80%) responded to treatment for their paranasal
      sinus disease, a far higher proportion than with nasal polyps without pus. In
      conclusion, in patients who have nasal polyps without purulent secretions, be
      cautious about attributing any symptoms of facial pain or pressure as being due
      to their paranasal sinuses as it is more probable that it is coincidental and the
      result of a neurological cause.

PMID- 11843936
TI  - Is cervical screening necessary in older women?

PMID- 11843937
TI  - Reasons for variation in coverage in the NHS cervical screening programme.
AB  - In order to investigate reasons for variation in coverage of cervical screening,
      data from standard Department of Health returns were obtained for all Health
      Authorities for 1998/1999. Approximately 80% of the variation between health
      authorities is explained by differences in age distribution and area
      classification. Considerable differences between Health Authority and Office of
      National Statistics (ONS) population figures in City and Urban (London) areas for
      the age group 25-29 years and for City (London) for age group 30-34 years,
      suggest an effect of list inflation in these groups. Coverage as a performance
      indicator may be more accurately represented using the age range 35-64 years.
      Using this narrower age range, the percentage of health authorities meeting the
      80% 5-year coverage target increases from 87% to 90%.

PMID- 11843938
TI  - Costs and benefits of cervical screening IV: valuation by women of the cervical
      screening programme.
AB  - OBJECTIVES: To assess the value of the cervical smear test to women, taking
      account of the positive and negative aspects of the cervical screening service.
      DESIGN: A postal survey. SETTING: Tayside Health Board region of Scotland.
      PARTICIPANTS: A sample of 2000 women aged 20-59. MAIN OUTCOME MEASURES: Maximum
      willingness to pay (WTP) for a cervical smear test. RESULTS: Women were prepared
      to pay 50.20 British pounds per smear on a 3-yearly basis. Willingness to pay was
      positively related to income, but unrelated to age and whether or not the
      respondent had previously had a smear. CONCLUSIONS: Previous studies have
      estimated the cost per screen or cost per life year saved by cervical screening.
      This study used the economic instrument of WTP to take account of other potential
      (dis)benefits to women. The value women place on having a smear was more than the
      cost to the National Health Service (NHS) of providing the service. The output of
      a WTP study is potentially useful at the policy level. Future work should explore
      both the value of alternative approaches to cervical screening, and the value of
      competing health care interventions.

PMID- 11843939
TI  - Variation in the assessment of adequacy in cervical smears.
AB  - OBJECTIVE: To assess the interobserver reproducibility of the diagnosis of
      'adequacy' of cervical smears according to the Bethesda System criteria in
      cervical smears. STUDY DESIGN: 358 cervical smears were obtained from three
      Italian cytopathological centres in 1998-99. All centres provided consecutively
      collected smears. The cervical smears were independently and blindly assessed by
      four cytologists. The screening was performed using a 10x objective and an
      additional evaluation of the percentage of cellularity was performed using a 4x
      objective. RESULTS: The proportion of smears assessed by the four cytologists as
      'adequate' ranged from 60% to 70%, the proportion of 'satisfactory for evaluation
      but limited by' ranged from 27% to 38%, and the proportion of 'inadequate smears'
      ranged from 2% to 4%. Full agreement in the assessment of smear adequacy was
      observed in 311 slides and disagreement was observed only in 47. The category
      'inadequate smear' was less reliable than the other two; however, the kappa value
      observed was acceptable. CONCLUSION: The present study shows that it is possible
      to achieve a high reproducibility in the assessment of smear adequacy, at least
      among expert cytologists who follow the Bethesda System criteria strictly.

PMID- 11843941
TI  - A comparative study: conventional preparation and ThinPrep 2000 in respiratory
      cytology.
AB  - In order to compare and contrast conventional preparation (CP) with ThinPrep 2000
      (TP) in respiratory cytology, 207 samples were divided equally and processed by
      the two different preparation methods, generating three CP and one TP slide per
      sample. No lesion identified by CP was missed by TP and there were no significant
      differences between TP and CP in the diagnostic categories. However, two cases of
      squamous cell carcinoma were detected on TP which had been classified as
      unsatisfactory and moderate squamous dyskaryosis, respectively, on CP. ThinPrep
      was found to be superior to CP in many respects as it provided standardized
      preparations in a greater proportion of cases and problems such as cell
      overlapping and background debris were markedly reduced. In several instances the
      diagnostic accuracy in CP was compromised by smears that were either too thick,
      too thin, or too scanty. Cell preservation was also better on TP when compared
      with CP, facilitating more accurate diagnosis and significantly reducing the
      primary screening and reporting time, especially of sputum samples. A major
      advantage of TP methodology is the fact that it facilitates optimal use of
      skilled cytotechnologists and streamlines the workflow in the laboratory.

PMID- 11843940
TI  - Personal view. Is it reality or an illusion that liquid-based cytology is better
      than conventional cervical smears?
AB  - Liquid-based cytology (LBC) has been heralded as the way forward for cervical
      screening, and as the answer to many of its problems. It is already used as a
      sole method of cell preparation in many private clinics in the UK. It is being
      used for colposcopy smears in many NHS clinics and is now being piloted for
      primary screening in three screening centres in England, as well as one in
      Scotland and one in Wales. LBC has been welcomed as a new technology because it
      deals with the problem of specimen adequacy at source, removing responsibility
      for slide preparation and fixation from the clinician or nurse. It provides
      uniformly well-fixed preparations that are free of inflammatory exudate and
      blood, and seem easier to screen than conventional smears. There are many
      articles in the world literature suggesting that LBC is more accurate than
      conventional screening, and it is thought likely to reduce the number of false
      negative tests. The main reasons for piloting LBC in the NHS Cervical Screening
      Programme (NHSCSP) lie in its potential for reducing screening times and for
      reducing the numbers of repeats for inadequate tests. LBC is expensive in terms
      of equipment, capital costs, maintenance, consumables, training, technical
      preparation time, transportation and disposal of liquid media. Its costs could be
      justified if they were offset by the money saved from reduced screening time and
      repeat tests, but only if its accuracy in terms of sensitivity and specificity
      were proven to be equal to or better than conventional cytology. Although that is
      generally held to be true by the public and medical profession alike, there is
      very little hard evidence to support it.

PMID- 11843942
TI  - Fine needle aspiration cytology of thyroid nodules: how accurate is it and what
      are the causes of discrepant cases?
AB  - Fine-needle aspiration cytology (FNAC) is widely accepted as the most accurate,
      sensitive, specific and cost-effective diagnostic procedure in the assessment of
      thyroid nodules and helps to select people preoperatively for surgery. The
      purpose of this study was to evaluate the results of thyroid FNAC in our
      institution and to determine the reasons for discrepancies between the
      cytological and histological diagnosis. We evaluated the cytological and
      histological results of 254 FNACs obtained from 231 patients who underwent
      subsequent thyroid surgery. All of the material was blindly reviewed for quality
      control, by one experienced cytopathologist. All FNACs were carried out under
      ultrasound guidance. The cytological diagnosis was classified as benign,
      suspicious, malignant or unsatisfactory. The definitive histological study showed
      benign lesions in 195 of the 231 patients (84%). A benign diagnosis based on FNAC
      was correct in 105 of the 108 benign cases (97%). FNACs diagnosed as 'suspicious'
      resulted in a distribution of 49 benign (79%) and 13 malignant (21%) diagnoses.
      FNAC showed malignancy in 34 cases (13%) and in only one case did the final
      histology differ from cytology (correlation 97%). The percentage of FNACs that
      were inadequate for diagnosis was 20%. Review of cytological and histological
      slides did not lead to any change in the original diagnosis. Our study revealed a
      cytological-histological discrepancy (2%) in only 4 out of 231 cases over a
      period of 10 years, due to either a diagnostic or sampling error.

PMID- 11843943
TI  - Infantile fibromatosis--diagnosis by fine needle aspiration cytology.

PMID- 11843944
TI  - Procedures of rapid rescreening of Pap smears.

PMID- 11843945
TI  - Cytological findings of a primary mediastino-pulmonary leiomyosarcoma. Report of
      a case diagnosed by endoscopic ultrasonography-guided fine needle aspiration.

PMID- 11843947
TI  - Metabolic syndrome and type 2 diabetes: the need to reduce CV events.

PMID- 11843949
TI  - Attenuating CV risk factors in patients with diabetes: clinical evidence to
      clinical practice.
AB  - Individuals with diabetes are at high risk of cardiovascular (CV) disease, a risk
      that is significantly greater in the presence of traditional CV risk factors
      (hyperlipidaemia, hypertension, prothrombotic state). Glucose control and
      management of these risk factors decreases but does not eliminate CV events,
      reflecting the complexity of atherosclerosis. Novel risk factors (C-reactive
      protein, lipoprotein a, homocysteine, and endothelial dysfunction) have been
      proposed and are potentially modifiable. However, clinical trials data are not
      yet available to guide therapy. At this time, no single agent can achieve
      adequate risk reduction in patients with diabetes. Even with the use of multiple
      agents and classes of agents to manage CV risk, 75% of patients with diabetes are
      expected to die from CV causes. Despite the recent advances in primary and
      secondary prevention of CV events, new approaches are needed. Data from the Heart
      Outcomes Prevention Evaluation (HOPE) trial demonstrated that CV risk can be
      further reduced by the addition of the ACE inhibitor ramipril to the existing
      treatment regimen of high-risk patients with diabetes.

PMID- 11843950
TI  - Multiple CHD risk factors in type 2 diabetes: beyond hyperglycaemia.
AB  - Recent evidence from the United Kingdom Prospective Diabetes Study convincingly
      demonstrates that good glycaemic control is difficult to achieve and, despite its
      positive impact on microvascular complications, is not sufficient to reduce the
      risk of coronary heart disease (CHD). Syndrome X--a cluster of abnormalities
      associated with resistance to insulin-mediated glucose uptake that have been
      implicated in accelerating atherogenesis--provides a useful clinical concept to
      prevent CHD in patients with type 2 diabetes. Components of syndrome X can
      include hypertension, hyperinsulinaemia, dyslipidaemia, and a procoagulant state,
      changes that contribute to the development of atherosclerosis. Low-density
      lipoprotein cholesterol (LDL-C) levels are usually close to normal, but the LDL-C
      is present in abnormally small and dense particles. Triglyceride levels are
      elevated and are associated with an increase in postprandial accumulation of
      atherogenic, remnant lipoprotein particles. High-density lipoprotein cholesterol
      levels are typically low. This particular dyslipidaemia, along with
      hyperinsulinaemia, induces expression of plasminogen activator inhibitor-1,
      contributing to a prothrombotic state. In addition, plaque formation may be
      accelerated in insulin-resistant subjects by increased expression of adhesion
      molecules on endothelial cells and increased rate of monocyte adhesion to
      cultured endothelial cells. Syndrome X and type 2 diabetes are associated with
      multiple abnormalities that enhance the atherosclerotic process. The
      opportunities for new therapeutic approaches to reduce cardiovascular risk will
      undoubtedly evolve along with our understanding of the complex factors
      responsible for insulin resistance, compensatory hyperinsulinaemia, and CHD.

PMID- 11843951
TI  - What should the role of ACE inhibitors be in the treatment of diabetes? Lessons
      from HOPE and MICRO-HOPE.
AB  - Experimental and clinical evidence suggest that angiotensin converting enzyme
      (ACE) inhibition may reduce cardiovascular (CV) risk by directly affecting
      endothelial dysfunction, atherosclerosis and thrombus formation. These direct
      effects are in addition to effects on vascular tone or pressure. The Health
      Outcomes and Prevention Evaluation (HOPE) study assessed the role of an ACE
      inhibitor ramipril in reducing CV events in 9297 patients > or = 55 years who
      were at high risk of CV events but did not have left ventricular dysfunction,
      heart failure, or high blood pressure at the time of study entry. In the overall
      HOPE population, the risk of the primary composite outcome (cardiovascular death,
      myocardial infarction, or stroke) was reduced by 22% (p < 0.001), and in patients
      with diabetes plus one other CV risk, it was reduced by 25% (p = 0.0004).
      Ramipril treatment achieved risk reduction in patients with mild renal
      insufficiency (serum creatinine > or = 1.4 mg/dl). Ramipril treatment did not
      increase adverse events in patients with renal insufficiency. The Study to
      Evaluate Carotid Ultrasound changes in patients treated with Ramipril and Vitamin
      E (SECURE) demonstrated that ramipril 10 mg significantly reduced the rate of
      carotid intimal medial thickening, suggesting a direct effect on atherosclerotic
      progression.

PMID- 11843952
TI  - Reducing the risk of stroke in diabetes: what have we learned that is new?
AB  - Given the significant public health impact of stroke and the identification of
      nonmodifiable (age, gender, race/ethnicity) and modifiable (blood pressure,
      diabetes, lipid profile, and lifestyle) risk factors, early prevention strategies
      should be initiated. When a patient suffers a stroke, the focus of care becomes
      prevention of future events. For the patient with diabetes, comprehensive medical
      management of ischaemic stroke (primary or secondary prevention) includes
      antihypertensive and lipid-lowering therapy, as well as antiplatelet therapy.
      Despite the cerebrovascular risk reduction with these modalities, clearly new
      agents are needed. The Heart Outcomes Prevention Evaluation (HOPE) study provides
      compelling evidence that treatment with the angiotensin converting enzyme
      inhibitor, ramipril, can further reduce the risk of stroke in high-risk patients
      by mechanisms other than lowering blood pressure. In HOPE, patients were
      normotensive at baseline. Therefore, for the first time, in a patient population
      without left ventricular dysfunction, the effects of an ACE inhibitor ramipril on
      reducing stroke risk were demonstrated. Ramipril 10 mg achieved a significant 33%
      reduction in stroke among patients with diabetes. Based on the HOPE study, the
      recently published American Heart Association guidelines for the primary
      prevention of stroke recommend ramipril to prevent stroke in high-risk patients
      and in patients with diabetes and hypertension. Wide-scale adherence to these
      guideline recommendations for the prevention of primary and secondary stroke
      would significantly benefit the public health.

PMID- 11843955
TI  - Nomenclature for factors of the HLA System, update July 2001.

PMID- 11843954
TI  - The HLA Dictionary 2001: a summary of HLA-A, -B, -C, -DRB1/3/4/5 and -DQB1
      alleles and their association with serologically defined HLA-A, -B, -C, -DR and 
      DQ antigens.
AB  - This report presents the serological equivalents of 123 HLA-A, 272 HLA-B and 155
      HLA-DRB1 alleles. The equivalents cover over 64% of the presently identified HLA
      A, -B and -DRB1 alleles. The dictionary is an update of the one published in 1999
      (<1>Schreuder et al., 1999, Tissue Antigens, 54, 409) and also includes
      equivalents for HLA-C, DRB3, DRB4, DRB5 and DQB1 alleles. The data summarize
      information obtained by the WHO Nomenclature Committee for Factors of the HLA
      System, the International Cell Exchange (UCLA), the National Marrow Donor Program
      (NMDP) and individual laboratories. In addition, a listing is provided of alleles
      that are expressed as antigens with serological reaction patterns that differ
      from the well-established HLA specificities. The equivalents provided will be
      useful in guiding searches for unrelated hematopoietic stem cell donors in which
      patients and/or potential donors are typed by either serology or DNA-based
      methods. These equivalents will also serve typing and matching procedures for
      organ transplant programmes where HLA typings from donors and from recipients on
      waiting lists represent mixtures of serological and molecular typings. The tables
      with HLA equivalents and a questionnaire for submission of serological reaction
      patterns for poorly identified allelic products will also be available on the
      WMDA web page: www.worldmarrow.org

PMID- 11843956
TI  - Nomenclature for factors of the HLA System, update August 2001.

PMID- 11843957
TI  - The African enigma: low prevalence of gastric atrophy, high prevalence of chronic
      inflammation in West African adults and children.
AB  - BACKGROUND: Helicobacter pylori infection is very common in Africa, yet peptic
      ulcer disease and gastric malignancy are rare. AIM: The aim of this study was to
      quantify mucosal responses to H. pylori in Gambian adults and children and to
      estimate the prevalence of antibodies to bacterial virulence factors (cagA and
      vacA) in a symptomatic population. PATIENTS AND METHODS: Adults (mean 36 SD 12
      years) with dyspepsia and children (mean 1.4 years SD 0.4 years) with
      malnutrition underwent gastroscopy with biopsy. Blood was simultaneously drawn
      for cagA and vacA antibody status. Histopathological scoring used the modified
      Sydney classification. RESULTS: Both adults (n = 45) and children (n = 37) mainly
      demonstrated chronic mild antral inflammation. Only 2/83 cases of focal atrophy
      (GA) and 4/83 cases of intestinal metaplasia (IM) were observed. Adults tended to
      demonstrate more frequent acute (AI) and chronic inflammation (CI) (38% compared
      with 18% and 85% compared with 72%, respectively). Sixty-seven percent of
      children were cagA IgG+ and 21% vacA IgG+ and 93% of adults were IgG cagA+ and
      86% vacA+. There were no differences in mucosal responses between those who were
      cagA or vacA positive compared with those who were negative. CONCLUSION: Gambian
      adults and children mount a CI response to H. pylori but GA, IM and AI are
      uncommon. cagA and vacA are commonly expressed in Gambian strains of H. pylori.
      Further studies are needed in order to confirm that GA and IM are not late
      findings in old age.

PMID- 11843958
TI  - The relationship between Helicobacter pylori infection, the virulence genotypes
      of the infecting strain and gastric cancer in the African setting.
AB  - BACKGROUND: The relationship between Helicobacter pylori infection and gastric
      carcinoma remains controversial, especially in the African setting where
      infection is common, while gastric cancer is perceived to be uncommon, the basis
      of the so called 'African enigma'. This discrepancy between infection and the
      development of disease is commonly attributed to differences in host, environment
      and bacterial factors. Interest in the bacterial factors has focused on
      heterogeneity in the so-called 'virulence genes'. AIM: The aim of this
      prospective, case-controlled study was to establish whether H. pylori infection
      is significantly associated with gastric cancer and to investigate whether
      gastric cancer is associated with genotypically distinct (as it relates to the
      candidate virulence genes) organisms in this population. METHODS: Patients with
      histologically confirmed gastric cancer were matched with nonulcer dyspeptic
      controls for age (within 5 years), gender and ethnicity. Helicobacter pylori
      status was determined by RUT, histology, culture and serology (locally validated
      and used as default determinant of H. pylori status). Tumors were classified
      according to the Lauren classification. The 'virulence genotype' of 17 paired
      culture samples was determined by previously described and validated molecular
      techniques (cagA presence, vacA alleles, structure of the cag pathogenicity
      island and analysis of the iceA alleles). Categorical variables were analysed by
      the chi2 test. RESULTS: Forty-eight patients (median age 59 years) could be
      adequately matched to controls. 39/48 (81%) cases and 43/48 (90%) controls were
      H. pylori positive (NS). Significant differences in the virulence genotypes of
      infecting strains were noted: vacAs2-controls 24%, cases 0%, p < .00001; vacAs1
      present - cases 100%, controls 76%, p < .05; cagA-3'-length > 650 bp - cases 47%,
      controls 0%, p < .002; cag pathogenicity island intact - cases 82%, controls 43%,
      p < .04; iceA1 - cases 53%, controls 6%, p < .005. cagA was found in all
      subjects. CONCLUSION: This study indicates that, in this African population at
      least, there is no difference in the prevalence of H. pylori infection when
      comparing gastric cancer cases with matched controls. However, the findings
      suggest that gastric cancer may be associated with infection by organisms that
      are genotypically different from those not associated with disease.

PMID- 11843959
TI  - Immune response to a 26-kDa protein, alkyl hydroperoxide reductase, in
      Helicobacter pylori-infected Mongolian gerbil model.
AB  - BACKGROUND: The host immune response is thought to play an important role in the
      outcome of Helicobacter pylori infection. The successful development of the H.
      pylori-infected Mongolian gerbil model that mimics human disease has enabled
      study of the antibody response against H. pylori antigens. MATERIALS AND METHODS:
      Serum samples from ulcer and carcinogenesis models of H. pylori-infected gerbils
      were used to screen for H. pylori antigens that cause a humoral immune response
      in the infected hosts. H. pylori alkyl hydroperoxide reductase (AhpC) is one such
      antigen on which we report here. The tsaA gene encoding AhpC was amplified by PCR
      from H. pylori ATCC 43504 strain, cloned into pMAL(TM)-c2 expression vector and
      expressed in Escherichia coli. Maltose-binding protein fusion protein (MBP-AhpC)
      was purified by a MBP affinity column. Using purified recombinant AhpC protein as
      an antigen, the antibody response and changes of antibody levels against AhpC in
      the gerbil models were studied by Western blotting and ELISA. RESULTS: Antibody
      against AhpC was negative in the early stages of infection, and became positive
      in the gerbils with the emergence of gastric diseases such as chronic active
      gastritis, gastric ulcer and gastric cancer. The antibody levels (ELISA)
      increased gradually over time and were higher in gerbils with gastric ulcer than
      that in gerbils without ulcers. CONCLUSIONS: Use of the gerbil model that mimics
      human H. pylori infection is likely to provide insights into the role of H.
      pylori-specific antigens possibly related to the subsequent development of
      gastric diseases.

PMID- 11843960
TI  - T cell-mediated cytotoxicity via Fas/Fas ligand signaling in Helicobacter pylori
      infected gastric corpus.
AB  - BACKGROUND: Helicobacter pylori infection induces T helper-1 immune responses in
      inflamed mucosa. However, the role of T cell-mediated cytotoxicity in the
      induction of epithelial apoptosis is still unclear. The aim of this study was to
      investigate the involvement of the Fas/Fas ligand (Fas/Fas-L) system in the H.
      pylori-infected gastric corpus. MATERIALS AND METHODS: Gastric fundic biopsy
      specimens were taken from patients with and without H. pylori infection. The
      expression of Fas and Fas-L was examined by immunohistochemistry and RT-PCR.
      Subsets of gastric infiltrating T cells in the biopsy specimens were studied by
      immunohistochemistry and flow cytometry. In histological sections, apoptosis was
      detected by the TUNEL method. We studied the in vitro expression of Fas-L in
      peripheral T cells after stimulation with H. pylori antigen and interferon-gamma
      (IFN-gamma). The Fas-mediated in vitro cytotoxicity of activated T cells was
      assessed by flow cytometry. RESULTS: The numbers of CD4+ and CD8+ T cells were
      greater in H. pylori-infected subjects. Fas expression was abundantly increased
      on fundic gland epithelium, and Fas-L was detected on lamina propria mononuclear
      cells in H. pylori-infected mucosa. TUNEL-positive epithelial cells were also
      increased in H. pylori-infected subjects. H. pylori antigen and IFN-gamma induced
      Fas-L mRNA expression in both CD4+ and CD8+ T cells. In cytotoxic assay,
      activated T cells induced apoptosis in AGS cells, which could be significantly
      inhibited by neutralizing Fas-L antibody. CONCLUSIONS: T cell-mediated
      cytotoxicity via Fas/Fas-L signaling may contribute to the induction of apoptosis
      in gastric epithelial cells during H. pylori infection.

PMID- 11843961
TI  - Atrophic gastritis and intestinal metaplasia in Japan: results of a large
      multicenter study.
AB  - BACKGROUND: This study evaluated the relationship between Helicobacter pylori
      infection, atrophic gastritis and intestinal metaplasia in Japan. MATERIALS AND
      METHODS: This was a multicenter study performed in 21 centers in Japan. A total
      of 2455 individuals were enrolled. H. pylori status was determined by validated
      ELISAs. Atrophic gastritis was diagnosed by histology, endoscopy with Congo Red
      dye scattering or the Kimura-Takemoto endoscopic classification. RESULTS:
      Atrophic gastritis increased from 9.4% in those less than 20 years of age to >
      70% in those aged 60 or older and was strongly associated with H. pylori
      infection. The overall prevalence of atrophic gastritis in H. pylori infection
      was 82.9% (1272/1534) compared with 9.8% (90/921) among uninfected (OR = 44.8;
      95% CI = 34.7-57.8). Intestinal metaplasia was present in 43.1% (542/1258) of H.
      pylori positive persons compared with 6.2% (51/823) among the uninfected (OR =
      11.5; 95% CI = 8.5-15.5). Atrophic gastritis in H. pylori positive Japanese was
      very high in the younger generation (38.5% in those aged 20 or less and 58.5% in
      those 21-30). CONCLUSIONS: Atrophic gastritis and intestinal metaplasia were
      strongly associated with H. pylori and not with aging. The fall in prevalence of
      H. pylori in Japan has not been associated with a corresponding fall in the
      prevalence of atrophic gastritis among those with H. pylori infection. The high
      prevalence of the precursor lesion, atrophic gastritis with intestinal
      metaplasia, among those with H. pylori infection suggests that the risk of
      development of early gastric cancer will continue to remain high in Japan.

PMID- 11843962
TI  - Identification of environmental stress-regulated genes in Helicobacter pylori by
      a lacZ reporter gene fusion system.
AB  - BACKGROUND: Helicobacter pylori persists in the human stomach for decades. This
      requires an efficient adaptation of H. pylori to the gastric niche and involves
      the regulation of bacterial genes in response to environmental stress. Efficient
      molecular tools to identify regulated H. pylori genes are scarce, therefore we
      developed a genomic lacZ reporter gene fusion system in H. pylori to screen for
      stress-regulated genes. MATERIALS AND METHODS: The integration vector pBW was
      constructed and used to generate random genomic lacZ fusions in H. pylori. Two
      hundred-and-fifty H. pylori transformants were selected from this library,
      replica-plated and screened for differential lacZ expression after exposure to
      two environmental stress conditions: increased temperature (42 degrees C), and
      iron-limitation. RESULTS: From a library of H. pylori transformants with random
      genomic transcriptional lacZ fusions, two stress-regulated H. pylori loci were
      identified. The transcription of a gene of unknown function (designated hsp12)
      was increased by incubation at 42 degrees C. The transcription of a locus,
      consisting of the three fumarate reductase subunit genes (frdCAB) and the HP0190
      gene from H. pylori strain 26695, was decreased under iron-limitation.
      CONCLUSIONS: This is the first time that a genomic transcriptional lacZ reporter
      gene H. pylori library has been used as a tool for the fast and efficient
      identification of environmental stress-regulated H. pylori genes.

PMID- 11843963
TI  - Helicobacter pylori infection is associated with a decreased risk of developing
      oesophageal neoplasms.
AB  - BACKGROUND: The role of Helicobacter pylori infection in the development of
      oesophageal malignancies was investigated through a multivariate conditional
      logistic regression analysis in a nested case-control study. METHODS: Blood
      samples and a questionnaire on smoking and alcohol habits were collected from a
      cohort of 32,906 city residents during a health-screening programme between 1974
      and 1992. Forty-four cases of oesophageal cancer and 149 matched controls were
      selected. The mean interval between screening and cancer diagnosis was 11.9
      years. H. pylori seropositivity was determined by an enzyme-linked immunosorbant
      assay measuring IgG. Occupation was included in the statistical analysis as an
      indicator of socio-economic status. RESULTS: Helicobacter pylori seropositivity
      was present in 10 of the cases (22.7%) and 67 of the controls (45.0%). In a
      multivariate model, with adjustment for occupation, tobacco and alcohol
      consumption, the odds ratio for developing an oesophageal malignancy when
      infected with H. pylori was 0.29 (95% confidence interval (CI): 0.12-0.67).
      Current smokers had an odds ratio of 17.3 (95% CI: 3.0-99.4) and the odds ratio
      for ex-smokers was 5.9 (95% CI: 1.15-29.9). High alcohol consumption was no
      longer significantly associated with oesophageal neoplasms after tobacco smoking
      was included into the model, odds ratio 1.22 (95% CI: 0.46-3.2). The protective
      effect of H. pylori was more pronounced for oesophageal adenocarcinoma (seven
      cases, odds ratio 0.16, 95% CI: 0.00-1.06) than for squamous-cell carcinoma (29
      cases, odds ratio 0.41, 95% CI: 0.14-1.2). CONCLUSIONS: Helicobacter pylori
      infection is associated with a decreased risk of developing an oesophageal
      malignancy. Current smokers and ex-smokers have instead a definite increased risk
      of oesophageal neoplasms.

PMID- 11843964
TI  - Distribution of distinct vacA, cagA and iceA alleles in Helicobacter pylori in
      Hong Kong.
AB  - BACKGROUND: There is a substantial genetic heterogeneity among Helicobacter
      pylori strains, and certain genotypes have been suggested to be associated with
      the virulence of this pathogen. The aim of this study was to investigate the
      distribution of H. pylori vacA, cagA and iceA genotypes and their association
      with duodenal ulcer disease in Hong Kong. MATERIALS AND METHODS: Gastric biopsies
      of 72 H. pylori infected patients were analyzed by specific polymerase chain
      reactions. RESULTS: Of the 72 cases, 69 (95.8%) had vacA signal sequence s1c
      strains, and three (4.2%) had s1a strains. vacA middle region sequences, m1b and
      m2, were detected in 23 (31.9%) and 46 (63.9%), respectively. Six (8.3%) cases
      contained multiple vacA subtypes. vacA s2 allele was only observed in three
      (4.3%) cases, which were also infected with s1c subtype. cagA was present in 64
      (88.9%) of 72 patients, and iceA1 subtype was detected in 46 (63.9%) cases.
      Neither cagA nor vacA and iceA were associated with duodenal ulcer disease.
      CONCLUSION: The distribution of vacA, cagA and iceA alleles in H. pylori strains
      in Hong Kong is similar to that in east Asia. There is a difference in the
      distribution of genotypes between strains in Hong Kong and those in mainland
      China, although strains in the two regions exhibit a very close relation. The
      association of these virulence genes and duodenal ulcer disease needs
      reappraisal, particularly under geographic considerations.

PMID- 11843965
TI  - The effect of Helicobacter pylori eradication on gastric juice and blood ammonia
      concentrations and on visual evoked potentials in cirrhotics.
AB  - BACKGROUND: The primary source of ammonia is the gut. Ammonia can also be
      generated by the urease activity of Helicobacter pylori in the gastric mucosa.
      The aim of this study was to investigate the effect of H. pylori eradication on
      blood and gastric juice ammonia levels and on visual evoked potential (VEP)
      recordings in cirrhotic patients. MATERIALS AND METHODS: Male patients with
      cirrhosis and H. pylori infection were prospectively evaluated. All patients were
      given triple regimen for eradication for 10 days. Gastroscopy together with
      gastric juice sampling for ammonia and mucosal sampling for H. pylori status was
      performed before and after therapy. Gastric juice and blood ammonia levels were
      measured and VEP recordings were obtained before and after treatment. RESULTS:
      Twenty-seven patients were included in the study. Patients with overt clinical
      hepatic encephalopathy were excluded from the study. Twenty-four out of twenty
      seven patients became H. pylori-negative after the treatment. Ammonia
      measurements and VEP recordings were evaluated in the 24 patients in whom
      eradication was successful. A slight but statistically significant decrease in
      blood and a considerable decrease in gastric juice ammonia levels were observed
      after treatment [from 44.23 micromol/l to 41.6 micromol/l compared with 3234
      micromol/l to 2709 micromol/l, respectively (p <.05)] in patients in whom H.
      pylori was eradicated. VEP recordings were abnormal in 14 out of 24 patients
      before the treatment. Only four of these 14 patients with abnormal recordings
      showed improvement. (p > .05). CONCLUSIONS: Helicobacter pylori eradication in
      cirrhotics decreases blood and gastric juice ammonia concentrations whereas it
      does not provide an improvement in VEP recordings.

PMID- 11843966
TI  - Seroprevalence of Helicobacter pylori infection in Siberia.
AB  - BACKGROUND: Despite many population-based epidemiological studies of Helicobacter
      pylori prevalence in different parts of the world, Russia still represents a
      'blank spot' in this map. The aims of the present study were to evaluate the
      seroprevalence of H. pylori infection among the population of Siberia and to
      assess whether there is an association between abdominal symptoms and H. pylori
      positivity in our population. METHODS: Six hundred and forty-nine adults from
      five regions of Siberia and the Far East, and 79 children and adolescents from
      Novosibirsk participated in the study. Antibodies against H. pylori (IgG) were
      detected in serum using ELISA. RESULTS: The total percentage of infected adults
      varied from 70% to 92% depending on the region, and was somewhat lower in three
      populations living to the north of the 60th latitude compared with those under
      the 60th latitude. A lack of association was found between the presence of H.
      pylori and the gender, age and abdominal symptoms. Almost maximum prevalence of
      H. pylori infection occurred by 30 years of age with only a minor increase in
      older age groups. Half the children were infected with H. pylori by the age of
      15. CONCLUSIONS: Helicobacter pylori infection is widespread among the Siberian
      populations with some trend in its prevalence to decrease northward. In Siberia
      age-specific prevalence rates of H. pylori infection are similar to those usual
      for developing countries.

PMID- 11843968
TI  - Long-term reliability and observer comparisons in the radiographic diagnosis of
      periapical disease.
AB  - AIM: The aim of this study was to evaluate and compare the long-term diagnostic
      consistency of two examiners, an endodontist and a radiologist, and to make
      comparisons with findings recorded by an observer with more recent scientific and
      clinical experience in endodontics. METHODOLOGY: Three groups, each consisting of
      20 full mouth series of intraoral radiographs, with 79, 93 and 85 endodontically
      treated roots, respectively, were successively evaluated for periapical disease.
      Evaluations were at first performed separately by the three observers.
      Disagreement and difficult, borderline cases were subjected to joint evaluation.
      Intra- and interexaminer comparisons were made. For two of the observers the
      observations were compared with findings recorded several years before for the
      same cases in the same radiographs. RESULTS: The intra- and interobserver long
      term reliability of the two original examiners resulted in 83% overall agreement,
      the kappa values were 0.54, 0.57 and 0.53. Comparisons between all three
      observers disclosed 82%, 85% and 86% agreement and kappa values 0.55, 0.58 and
      0.60. The joint evaluations and decisions did not indicate a dominating influence
      from any of the observers. CONCLUSIONS: The long-term reliability of the two
      original observers was judged as being satisfactory. All three observers judged
      the overall disease status of the material in the same way. The joint discussions
      of selected cases might reduce observer variation to an acceptable level, avoid a
      number of false recordings and increase the reliability and validity of the
      findings.

PMID- 11843967
TI  - Endodontic implications of the maxillary sinus: a review.
AB  - The anatomical and clinical significance of the maxillary sinus in relation to
      conventional and surgical endodontic therapy is considered. The discussion
      includes a review on the development, anatomy and physiology of the maxillary
      sinus, the diagnostic evaluation of the sinus and the differential diagnosis of
      sinusitis. Endodontic implications of the maxillary sinus include extension of
      periapical infections into the sinus, the introduction of endodontic instruments
      and materials beyond the apices of teeth in close proximity to the sinus and the
      risks and complications associated with endodontic surgery.

PMID- 11843969
TI  - A new technique for the study of periapical bone lesions: ultrasound real time
      imaging.
AB  - AIM: This study describes the use of a real time-ultrasound imaging technique
      (echography) for the study of periradicular lesions. METHODOLOGY: Twelve patients
      with periapical lesions of endodontic origin, diagnosed with conventional
      clinical and radiographic examination, were examined further using echography at
      the site of the diagnosed lesions. Each lesion was echographically characterized
      and described by an expert echographist together with an endodontist. Once the
      major echographic features were identified, information on the size of the
      lesion, its content, and its vascular supply was obtained and recorded. A
      tentative differential diagnosis between a cyst and a granuloma was made based on
      the data. RESULTS: In all cases it was possible to obtain an echographic image.
      It was also possible to measure the lesions, to evaluate their content and to
      view their vascularization in different regions of the mouth. CONCLUSIONS:
      Ultrasound real time imaging is a promising diagnostic technique in
      endodontology, but further work is required to refine the process.

PMID- 11843970
TI  - Cytotoxicity of resin-, zinc oxide-eugenol-, and calcium hydroxide-based root
      canal sealers on human periodontal ligament cells and permanent V79 cells.
AB  - AIM: The purpose of this study was to determine the cytotoxicity of three
      different types of root canal sealer on human periodontal ligament (PDL) cells
      and a permanent hamster cell line (V79 cells). METHODOLOGY: Set specimens from
      two resin based sealers (AH26 and AHPlus), three zinc oxide-eugenol-based sealers
      (Canals, Endomethasone and N2) and one calcium hydroxide-based sealer (Sealapex)
      were eluted with culture medium for 1, 2, 3 and 7 days. Cytotoxicity was judged
      using tetrazolium bromide reduction assay on human primary PDL cells and V79
      cells derived from a Chinese hamster. RESULTS: The results showed that elutes
      from resin-based, zinc oxide-eugenol-based, and calcium hydroxide-based sealers
      were cytotoxic to primary human PDL cultures and V79 cells. Calcium hydroxide
      based sealer was the least toxic sealer amongst the chemicals tested in both
      cultures. The cytotoxic response decreased in an order of N2 > Endomethasone >
      AH26 > AHplus > Canals > Sealapex. CONCLUSIONS: The sensitivity of toxicity
      depended on the materials tested and the cell culture system used. Thus, the use
      of both permanent and primary cells is recommended for screening of the cytotoxic
      effects of root canal sealers. In addition, the results confirmed that root canal
      sealers constantly dissolve when exposed to an aqueous environment for extended
      periods, possibly causing moderate or severe cytotoxic reactions. Use of calcium
      hydroxide-based material as a root canal sealer initially may result in a more
      favourable response to periradicular tissues.

PMID- 11843971
TI  - Developmental changes and regional differences in histochemical localization of
      hyaluronan and versican in postnatal molar dental pulp.
AB  - AIM: The main aim of this study was to investigate the developmental changes in
      the distribution patterns of hyaluronan (HA) and versican in postnatal rat molar
      dental pulp, in order to confirm the hypothesis that the distribution of both
      molecules can vary with physiological conditions in the dental pulp. METHODOLOGY:
      Thirty postnatal Sprague-Dawley rats, 1, 7, 14, 21, 28, 35, 42 and 49 days old,
      were used for this study. Immunohistochemistry for versican with monoclonal
      antibodies 12C5 and CS-56 and histochemical staining for HA with HA-binding
      protein were applied to paraffin sections of the mandibular first molars at each
      age. RESULTS: At day 1, both molecules were evenly distributed in the interior
      parts of the pulp, but strong reactions for both molecules appeared in the
      subodontoblastic layer of the coronal pulp by the completion of crown formation.
      However, a strong reaction for HA and a weak reaction for versican were seen in
      the subodontoblastic layer of the radicular pulp. Furthermore, a versican
      deficient, low-HA area first appeared in the interior of the coronal pulp at day
      42 and expanded at day 49. CONCLUSIONS: Distribution of hyaluronan and versican
      in the dental pulp varied with age and also showed regional differences between
      the coronal and the radicular pulp, and this supports the hypothesis described
      above.

PMID- 11843972
TI  - Vitality status of microorganisms in infected human root dentine.
AB  - AIM: This experimental study was initiated to establish a method for
      characterizing the vitality status of bacteria in infected human root dentine by
      differentiating between viable and dead microorganisms. METHODOLOGY: Twenty-four
      root segments of extracted human teeth were infected with either Streptococcus
      sanguinis or Enterococcus faecalis for 8 weeks. Baseline samples from root
      dentine (rd) were collected after 4 weeks. These were compared with samples taken
      at week 8 (control group: n = 12) and with samples collected at week 12 after
      calcium hydroxide treatment for four weeks (test group: n = 12). After marking
      viable and dead bacterial cells by two fluorescent dyes, the portion of viable
      bacteria (PVB) was determined, as well as the number of colony-forming units
      (CFU). RESULTS: Viable and dead bacteria were identified in all "rd" samples.
      PVBrd values were lower than PVB values of the bacterial suspension in the root
      canal lumen. In the control group, PVBrd and CFUrd did not markedly differ at
      week 4 and at week 8, regardless of the strain used. In the test group, viable
      but non-culturable sanguinis streptococci (mean PVBrd = 27%; CFUrd = 0) were
      detected, despite calcium hydroxide treatment. The viability of E. faecalis was
      not affected by calcium hydroxide. CONCLUSIONS: Fluorescence labelling of
      bacteria in human root dentine gives valuable additional information about their
      vitality status compared to the parameter CFU. The method may be suitable for
      following the fate of bacteria in dentinal tubules, for example in the presence
      of intracanal dressings.

PMID- 11843973
TI  - A survey of methods used for post removal in specialist endodontic practice.
AB  - AIM: The aims of this study were to determine the attitudes of endodontists
      toward the risk of root fracture when removing posts and to determine which
      methods they commonly used to remove posts from root-filled teeth. METHODOLOGY: A
      survey was sent to all 74 members of the Australian and New Zealand Academy of
      Endodontists. The survey was divided into three parts to gather information
      concerning root canal retreatment performed in specialist endodontic practice,
      attitudes about the risk of root fracture when removing posts and the methods
      used to remove different post systems. RESULTS: Responses were received from 62
      (84%) of the Academy members. When a post was present in a tooth that required
      root canal retreatment, 66% of the endodontists preferred to remove the post,
      whilst 27% considered either post removal or periapical surgery. Forty-five per
      cent reported that a root fracture had occurred during post removal, but this
      represented less than 0.002% of the estimated number of posts removed by all
      respondents. Ultrasonic vibration was the most common method used to remove
      posts, although post removal devices were used more often in anterior teeth; the
      Eggler post remover was the most commonly used device. CONCLUSIONS: Most
      endodontists preferred to remove posts rather than perform periapical surgery.
      Few root fractures were reported. Ultrasonic vibration was the most common method
      used to remove posts from all tooth types, with the Eggler post remover used most
      commonly for posts in anterior teeth.

PMID- 11843974
TI  - Interleukin-1beta and tumour necrosis factor-alpha levels in periapical exudates.
AB  - AIM: The aim of this study was to determine IL-1beta and TNF-alpha levels in
      periapical exudates and to evaluate their relationship with clinical and
      radiological findings. METHODOLOGY: Periapical exudates were collected from root
      canals of 35 single-rooted teeth using absorbent paper points. IL-1beta and TNF
      alpha levels were determined by enzyme-linked immunosorbent assays. The samples
      were divided into two groups according to the presence or absence of clinical
      signs including swelling and/or fistula, pain on palpation and/or percussion, and
      pus discharge from canals. Periapical exudate samples were divided into two
      groups according to size of periapical radiolucent area. RESULTS: The mean
      concentration of IL-1beta (72.79 ng mL-1) in periapical exudates was
      approximately 12-fold higher than TNF-alpha(6.17 ng mL-1). There was no
      significant correlation between these cytokines (P > 0.05). IL-1beta levels in
      canals with larger radiolucent areas (long axis > or =1 cm) were significantly
      higher than those with small areas (P < 0.05). There was a tendency toward higher
      levels of IL-1beta in groups with clinical signs, but the differences were not
      significant (P > 0.05). CONCLUSIONS: Periapical exudate levels of both cytokines
      failed to reflect periapical disease state.

PMID- 11843975
TI  - Accuracy of a new apex locator: an in vitro study.
AB  - AIM: The purpose of this study was to test in an in vitro model the accuracy of a
      Bingo 1020 electronic apex locator, to compare the results to those of a well
      known apex locator, Root ZX, as well as to those of the radiographic method of
      tooth length determination. METHODOLOGY: A total of 120 extracted teeth,
      preserved in Thymol solution and kept refrigerated, was used for the study. The
      experiment was performed on single-rooted teeth and on one-root canal, chosen
      randomly, in multirooted teeth. The teeth were randomly divided into 12 groups of
      10 teeth each. After access preparation, the actual length (AL) was measured. The
      teeth were embedded in an alginate model specially developed for testing apex
      locators. Electronic tooth length measurements (EL) were carried out prior to
      root canal preparation using the two electronic apex locators (EAL) - Root ZX and
      Bingo 1020; three measurements were taken and an average computed. After the
      third measurement, the file was left in the root canal and a periapical
      radiograph was taken. The radiographic length (RL) was recorded by measuring the
      file length from the coronal reference point to the tip of the file. Each root
      canal was then prepared to a no. 40 K-file diameter using a standardized
      technique; saline was used for irrigation. Upon completion of the root canal
      preparation, EL measurements were taken by each EAL in dry conditions and with
      different irrigation solutions. Each measurement was repeated three times. The RL
      was recorded according to the last EL measurement. Results were subjected to
      statistical analysis. RESULTS: In all parameters tested, a significant
      statistical difference was found between Bingo 1020 and the Root ZX. Measurements
      obtained using the Bingo 1020 were consistently closer to the AL (0.08 mm) than
      those obtained using the Root ZX. Both EALs measured the tooth length with great
      accuracy and a positive correlation of 0.76 (P = 0.00) existed between the two
      devices. No significant difference was found between the two apex locators when
      measurements were taken with the different irrigants (P = 0.34) and the content
      of the root canal did not affect the accuracy of the measurements. Lengths
      obtained by calculations from the radiographs were longer than the AL as well as
      the length obtained by both EALs (P = 0.00). CONCLUSIONS: The Bingo 1020 proved
      to be as reliable as Root ZX and was user friendly. Under the experimental
      conditions, electronic measurements were more reliable than radiographs in the
      process of root length determination.

PMID- 11843976
TI  - Relationship between number of proximal contacts and survival of root canal
      treated teeth.
AB  - AIM: The present study tested the hypothesis that having two proximal contacts
      (PCs) at access is associated with improved survival of root canal treated (RCT)
      teeth, controlling for important presenting conditions, endodontic variables and
      restorative factors. METHODOLOGY: A treatment database at the University of Iowa
      College of Dentistry was used to identify permanent teeth undergoing obturation
      between 1 July 1985 and 31 December 1987. The list was restricted to teeth of
      patients with at least one dental visit in each two-year interval from 1985 to
      1996, and a simple random sample of 280 patients (n = 400 teeth) was selected.
      Dental charts, radiographs, and computerized databases were examined to ascertain
      variables of interest and to verify study inclusion criteria. Kaplan-Meier
      survival estimates were generated for the 221 teeth satisfying study inclusion
      criteria. Multivariate Cox models were developed, with standard errors adjusted
      to account for clustering of teeth within patients. RESULTS: The final Cox model
      showed that teeth with < or =1 PC at access were lost at a rate three times that
      of teeth with 2 PCs (hazard ratio = 3.1; 95% confidence interval = 1.9-5.1),
      controlling for tooth type, presence of radiographic caries at access, and
      presence of a crown before or after obturation. CONCLUSIONS: Because RCT teeth
      with two PCs at access experienced substantially better survival than teeth with
      fewer than two PCs, the influence of PCs on prognosis should be recognized during
      treatment planning. Future research should employ prospective study designs,
      capture additional variables, and provide data to support endodontic treatment
      decisions.

PMID- 11843977
TI  - Wanted: a standard for the recognition of rotary NiTi instruments.

PMID- 11843979
TI  - Insufficient sleep, cognitive anxiety and health transition in men with coronary
      artery disease: a self-report and polysomnographic study.
AB  - AIMS: To explore possible links between sleep quality, cognitive anxiety and the
      effects of sleep disturbances on health, daytime functioning and quality of life,
      for assessment in a larger study. Hypotheses were: (a) patients with coronary
      artery disease have insufficient sleep as measured by self-reported sleep and by
      polysomnography, (b) self-reported sleep is associated with polysomnographically
      measured sleep, (c) reduced sleep quality is associated with physical and mental
      health, and interferes with quality of life as measured by means of interviews
      and polysomnography, (d) reduced sleep quality is associated with reduced
      resilience to stress. BACKGROUND: It has become increasingly evident that poor
      sleep with sleep initiation difficulties is an independent risk factor for
      cardiac events among men, and requires more attention in clinical nursing
      practice. DESIGN: Descriptive, correlative and explorative study. SAMPLE: Forty
      four men, aged 45-70, about to undergo coronary artery bypass surgery at a
      Swedish University Hospital. RESEARCH METHODS: Interviews and 24-hour continuous
      ambulatory polysomnography were performed. For the interviews, the Uppsala Sleep
      Inventory, Spielberger State Anxiety Scale and the Nottingham Health Profile
      instruments were used. RESULTS: Seventeen patients (38.6%) had insufficient sleep
      and 12 had sleep initiation difficulties. Logistic regressions revealed that
      reduced stage 3-4 sleep predicted poorer overall health, initiation of sleep
      difficulties, predicted insufficient sleep and involuntary thoughts predicted
      fragmented sleep. Poorer quality of life was predicted by reduced deep sleep.
      Independent predictors for emotional distress were sleep efficiency below 85%,
      fragmented sleep and a daytime nap longer than 15 minutes. CONCLUSIONS: Objective
      sleep was associated with several subjective sleep variables. The results provide
      empirical support for significant variables included in a theoretical framework
      relating to sleep quality, cognitive anxiety, health and quality of life. A
      larger study is recommended that includes both men and women.

PMID- 11843980
TI  - Premature menopause: multiple disruptions between the woman's biological body
      experience and her lived body.
AB  - AIM OF THE STUDY: The aim of this phenomenological study was to find out what
      menopause was like as an experience for women who were not yet 40 years old.
      BACKGROUND: Women's bodies have naturally occurring rhythms and expected
      transitions related to their menstrual cycle. One transition that all women will
      experience, provided they live long enough, is menopause. Menopause involves
      hormonal changes that result, on average (for Australian women), in the cessation
      of menstruation around 51 years of age. When women experience menopause prior to
      the age of 40 years it is defined (medically) as premature. While there is
      abundant literature on menopause as a biological event, the experience of
      premature menopause has been paid little attention and dismissed as a 'mystery'.
      This study intended to uncover some of the so-called 'mystery' of the experience
      from the perspective of the women. RESEARCH METHODS: Hermeneutic phenomenology
      and feminist philosophy informed this study involving 35 women, all of whom
      volunteered to participate. They responded to newspaper articles, a radio
      announcement and through a midlife and menopause support centre. Thirty women
      engaged in separate face-to-face conversational style interviews. The remaining
      five women participated in a collaborative interview after some themes were
      identified through preliminary analysis of the transcripts of the one-on-one
      interviews. With the consent of participants, all interviews were audio-taped and
      later transcribed. FINDINGS: This study revealed that the experience of menopause
      came as a shock for the women--it was perceived as a major epiphany in their
      lives and they were confronted with a multitude of issues related to the timing
      of the event and their embodied understanding of menopause. The experience of
      menopause resulted in multiple disruptions in the women's lives. The women
      discussed many aspects of their lives that now seemed to be 'out of synchrony'.

PMID- 11843981
TI  - Illness attributions and myocardial infarction: the influence of gender and socio
      economic circumstances on illness beliefs.
AB  - AIM: To present findings from a study conducted between 1996 and 1998 to
      investigate participants' perceptions of illness causation following a myocardial
      infarction. RATIONALE: The underlying assumption of many practitioners is that
      perceptions of illness causation will influence emotions and adjustment to
      illness. DESIGN: Phenomenology was the research methodology used to examine
      perceptions of illness causation. A convenience sample was taken of 24 men and
      women who were admitted to a regional hospital in Victoria, Australia, with a
      provisional diagnosis of myocardial infarction. Participants were interviewed
      shortly after hospitalization, and interviews were taped, transcribed and
      thematically analysed. FINDINGS: Stress was the most commonly cited cause of
      illness. Men and women demonstrated distinct differences in illness attribution.
      Participants who verbalized concerns about their loss of autonomy and their
      subsequent ability for self-management were predominantly female and uniformly
      members of the lowest socio-economic group CONCLUSION: The article concludes with
      a discussion of implications of the findings for practice.

PMID- 11843982
TI  - A critical review of the arguments debating the role of the nurse advocate.
AB  - AIMS OF THE PAPER: This paper critically reviews the arguments for and against
      undertaking the role of nurse advocate. BACKGROUND: Advocacy has become a popular
      concept in nursing literature over the past two decades. By addressing issues of
      power and accountability, conclusions are drawn about the risks facing nurses who
      would practice patient advocacy. METHODS: Review and analysis of theoretical
      debate. RESULTS: Empirical evidence is sparse and philosophical arguments
      predominate in the field of patient advocacy. Humanistic arguments that promote
      advocacy as a moral imperative are compelling. However, in reality nurses appear
      to lack the power base to comply except by covert means. Informed consent with a
      knowledge of the consequences of undertaking such an intervention is as relevant
      to the nurse as it is to the patient. CONCLUSION: Nurses need to be empowered
      first, if they are to empower their patients. There may however, be more suitable
      candidates for the role of patient advocate and nurses should recognize that they
      do not have a monopoly on ethical decision making.

PMID- 11843983
TI  - Rethinking the birthing body: Cartesian dualism and perinatal nursing.
AB  - AIM OF THE PAPER: This paper highlights the pervasive influence of a Cartesian
      metaphysics on the medical paradigm and its profound impact on the practice of
      perinatal nursing in North America. BACKGROUND: Modern perinatal health care
      practices are founded on a Cartesian metaphysics that reduce birthing women to
      the status of object. Such practices deny the holistic aims of perinatal nursing.
      METHODS: A philosophical inquiry informs the tenets of this metaphysical
      discussion regarding the foundations of perinatal nursing practices. FINDINGS:
      Although perinatal health care is founded on a Cartesian metaphysics, an
      alternative paradigm of embodied practice is suggested as a way of viewing
      birthing women as embodied subjects. CONCLUSION: If the foundations of health
      care, which have been built on a Cartesian metaphysics, are not re-examined,
      perinatal nurses will be providing care that further reduce women to the status
      of object.

PMID- 11843984
TI  - Caring science and the science of unitary human beings: a trans-theoretical
      discourse for nursing knowledge development.
AB  - BACKGROUND: Two dominant discourses in contemporary nursing theory and knowledge
      development have evolved over the past few decades, in part by unitary science
      views and caring theories. Rogers' science of unitary human beings (SUHB)
      represents the unitary directions in nursing. Caring theories and related caring
      science (CS) scholarship represent the other. These two contemporary initiatives
      have generated two parallel, often controversial, seemingly separate and
      unrelated, trees of knowledge for nursing science. AIM: This paper explores the
      evolution of CS and its intersection with SUHB that have emerged in contemporary
      nursing literature. We present a case for integration, convergence, and creative
      synthesis of CS with SUHB. A trans-theoretical, trans-disciplinary context
      emerges, allowing nursing to sustain its caring ethic and ontology, within a
      unitary science. METHODS: The authors critique and review the seminal, critical
      issues that have separated contemporary knowledge developments in CS and SUHB.
      Foundational issues of CS, and Watson's theory of transpersonal caring science
      (TCS), as a specific exemplar, are analysed, alongside parallel themes in SUHB.
      By examining hidden ethical-ontological and paradigmatic commonalities, trans
      theoretical themes and connections are explored and revealed between TCS and
      SUHB. CONCLUSIONS: Through a creative synthesis of TCS and SUHB we explicate a
      distinct unitary view of human with a relational caring ontology and ethic that
      informs nursing as well as other sciences. The result: is a trans-theoretical,
      trans-disciplinary view for nursing knowledge development. Nursing's history has
      been to examine theoretical differences rather than commonalities. This trans
      theoretical position moves nursing toward theoretical integration and creative
      synthesis, vs. separation, away from the 'Balkanization' of different theories.
      This initiative still maintains the integrity of different theories, while
      facilitating and inviting a new discourse for nursing science. The result:
      Unitary Caring Science that evokes both science and spirit.

PMID- 11843985
TI  - Using chaos theory: the implications for nursing.
AB  - AIMS OF THE PAPER: The purpose of this paper is to review chaos theory and to
      examine the role that it may have in the discipline of nursing. BACKGROUND: In
      this paper, the fundamental ingredients of chaotic thinking are outlined. The
      earlier days of chaos thinking were characterized by an almost exclusively
      physiological focus. By the 21st century, nurse theorists were applying its
      principles to the organization and evaluation of care delivery with varying
      levels of success. Whilst the biological use of chaos has focused on pragmatic
      approaches to knowledge enhancement, nursing has often focused on the mystical
      aspects of chaos as a concept. CONCLUSIONS: The contention that chaos theory has
      yet to find a niche within nursing theory and practice is examined. The
      application of chaotic thinking across nursing practice, nursing research and
      statistical modelling is reviewed. The use of chaos theory as a way of
      identifying the attractor state of specific systems is considered and the
      suggestion is made that it is within statistical modelling of services that chaos
      theory is most effective.

PMID- 11843986
TI  - Does training in psychosocial interventions reduce burnout rates in forensic
      nurses?
AB  - BACKGROUND: Mental Health Nurses working in secure environments with patients
      suffering from serious mental illness have been shown to be at risk of clinical
      burnout syndrome, this can have adverse effects both on the nurses' health and
      the standards of care that they deliver. AIM: To evaluate the effect of
      Psychosocial Intervention Training (PSI) on the knowledge, attitudes and levels
      of clinical burnout in a group of forensic mental health nurses. DESIGN: Baseline
      assessments of knowledge, attitude and burnout were completed by asking a group
      of 33 nurses working in a medium secure psychiatric unit to complete
      questionnaires. Twenty of the nurses volunteered to be included in a PSI training
      course and were randomly allocated either to receive the training or to a waiting
      list control group. The duration of the training was 6 months and on completion
      subjects in the experimental and control group completed the questionnaires
      again. RESULTS: Staff in the experimental group showed significant improvements
      in their knowledge and attitudes about serious mental illness and a significant
      decrease in burnout rates, whilst staff in the control group showed a small but
      nonsignificant improvement in knowledge and attitudes, and increase in burnout.
      CONCLUSION: The findings suggest that providing forensic mental health nurses
      with a better understanding of serious mental illness and training them in a
      broader range of interventions, helps them to be more positive in their attitudes
      towards the clients that they work with and experience less negative effects of
      stress resulting from their caring role. The implications of this study for
      clinical practice and future research will be discussed.

PMID- 11843987
TI  - Challenging contemporary mental health policy: time to assuage the coercion?
AB  - BACKGROUND: In the United Kingdom (UK) and elsewhere throughout the world, the
      policy and legal frameworks that surround the provision of mental health care are
      becoming increasingly coercive. For example, emerging mental health policy in the
      UK includes a commitment to the introduction of compulsory treatment in the
      community. AIMS: In this paper, our aims are: to explore the context in which
      this more coercive mental health policy has arisen in the UK; to challenge the
      assumptions and the evidence that lie behind the introduction of proposed new
      mental health policies; and to consider the impact that a more coercive policy is
      likely to have on the practice of mental health nursing. DISCUSSION: In the UK,
      representatives of central government have declared that 'care in the community
      has failed'. This view has been reinforced by media representations of mental
      health issues. Policy documents have drawn attention to the risks posed by people
      with mental illnesses. Correspondingly, proposed initiatives emphasize the need
      to more closely 'manage' people with mental health problems, and set out a new
      legislative and policy framework to achieve this. We question the assumptions and
      evidence that underlie these planned new developments. We argue that, contrary to
      government assertions, there is no unequivocal evidence that 'community care' has
      failed. We observe, too, that people with mental health difficulties are often
      amongst the most vulnerable members of society. Finally, we consider the impact
      that a more coercive policy framework will have on the work of mental health
      nurses, and argue that the shift towards a more 'controlling' role is likely to
      run counter to what many nurses see as the 'core' of their work.

PMID- 11843988
TI  - Inequalities in health care provision: the relationship between contemporary
      policy and contemporary practice in maternity services in England.
AB  - AIM: The project Addressing Inequalities in Health: new directions in midwifery
      education and practice (Hart et al. 2001) was commissioned by the English
      National Board for Nursing, Midwifery and Health Visiting (ENB). Here, we draw on
      those research findings to consider current midwifery policy and practice in
      England. BACKGROUND: Little guidance on providing equality of care exists for
      midwives. The Code of Conduct [United Kingdom Central Council for Nursing,
      Midwifery and Health Visiting (UKCC) 1992] makes no specific requirement for
      midwives to address issues of inequalities of health in their practice. Recent
      policy documents emphasize the need to work towards reducing inequalities and to
      target practice to 'disadvantaged clients' without giving guidelines on how to
      identify and care for target groups. METHODS: In-depth studies of midwifery
      education and service provision were conducted in three very different parts of
      England. Three months of fieldwork were undertaken at each site, comprising a
      series of interviews with midwifery educators, managers, students, midwives and
      service users. Focus groups were also held and observation of classroom sessions
      and midwifery practice undertaken. Findings. A lack of clear and specific
      strategies concerning inequalities in health was evident at managerial level.
      Patchy knowledge of current policy was also evident amongst practising midwives.
      Specific projects with disadvantaged clients usually resulted from a particular
      midwife's personal interest or evident local need. All midwives emphasized the
      importance of 'equality of care'. How this was operationalized varied, and
      'individualized' or 'woman-centred' care was assumed to encompass the concept. In
      the few examples where care was systematically targeted in accordance with policy
      directives, the midwife's public health role was increased. CONCLUSION: In the
      absence of a co-ordinated strategic vision driven by managers, practitioners find
      difficulty in prioritizing care and targeting resources to disadvantaged clients
      in line with policy directives. Tensions between policy and practice in the care
      of 'disadvantaged' women clearly exist. Successful implementation of policy at
      practice level needs: commitment from managers; clarity of purpose in
      documentation; and provision of specific targets for practitioners. However, the
      latter should remain flexible enough for the delivery of care to be appropriate
      and sensitive to individual needs.

PMID- 11843990
TI  - A randomized, double-blind, placebo-controlled study of the efficacy and safety
      of donepezil in patients with Alzheimer's disease in the nursing home setting.
AB  - OBJECTIVES: To evaluate the safety and efficacy of donepezil in the management of
      patients with Alzheimer's disease (AD) residing in nursing home facilities.
      DESIGN: Twenty-four-week, randomized, multicenter, parallel-group, double-blind,
      placebo-controlled trial. SETTING: Twenty-seven nursing homes across the United
      States. PARTICIPANTS: Two hundred eight nursing home patients with a diagnosis of
      probable or possible AD, or AD with cerebrovascular disease; mean Mini-Mental
      State Examination (MMSE) score 14.4; mean age 85.7. MEASUREMENTS: The primary
      outcome measure was the Neuropsychiatric Inventory-Nursing Home Version (NPI-NH).
      Secondary efficacy measures were the Clinical Dementia Rating (Nursing Home
      Version)-Sum of the Boxes (CDR-SB), MMSE, and the Physical Self-Maintenance Scale
      (PSMS). Safety was monitored by physical examinations, vital signs, clinical
      laboratory tests, electrocardiograms (ECGs), and treatment-emergent adverse
      events (AEs). RESULTS: Eighty-two percent of donepezil- and 74% of placebo
      treated patients completed the trial. Eleven percent of donepezil- and 18% of
      placebo-treated patients withdrew because of AEs. Mean NPI-NH 12-item total
      scores improved relative to baseline for both groups, with no significant
      differences observed between the groups at any assessment. Mean change from
      baseline CDR-SB total score improved significantly with donepezil compared with
      placebo at Week 24 (P < .05). The change in CDR-SB total score was not influenced
      by age. Differences in mean change from baseline on the MMSE favored donepezil
      over placebo at Weeks 8, 16, and 20 (P < .05). No significant differences were
      observed between the groups on the PSMS. Overall rates of occurrence and severity
      of AEs were similar between the two groups (97% placebo, 96% donepezil).
      Gastrointestinal AEs occurred more frequently in donepezil-treated patients. In
      general, AEs were similar in older and younger donepezil-treated patients, with
      the majority of patients experiencing only AEs that were transient and mild or
      moderate in severity. Weight loss was reported as an AE more frequently in older
      patients, although a loss at last visit of >or=7% of screening weight occurred at
      the same rate in older and younger patients (9% of donepezil- and 6% of placebo
      treated patients). No significant differences between groups in vital sign
      changes, bradycardia, or rates of clinically significant laboratory or ECG
      abnormalities were observed. CONCLUSION: Patients treated with donepezil
      maintained or improved in cognition and overall dementia severity in contrast to
      placebo-treated patients who declined during the 6-month treatment period. The
      safety and tolerability profile was comparable with that reported in outpatient
      studies of donepezil. These findings also suggest that advanced age, comorbid
      illnesses, and high concomitant medication usage should not be barriers to
      donepezil treatment. Given the apparent improvement in behavior in the placebo
      group, and the high use of concomitant medications in both groups, the impact of
      donepezil on behavior in the nursing home setting is unresolved and merits
      further investigation. In summary, effects on cognition, overall dementia
      severity, and safety and tolerability findings are consistent with previous
      findings in outpatients and support the use of donepezil in patients with AD who
      reside in nursing homes.

PMID- 11843991
TI  - Caregivers' utilization of health services: results from the Medicare Alzheimer's
      Disease Demonstration, Illinois site.
AB  - OBJECTIVES: The purpose of this study is to examine the effect of the Medicare
      Alzheimer's Disease Demonstration and Evaluation (MADDE) conducted in Illinois on
      the use of health services and Medicare expenditures by caregivers of persons
      with dementia. DESIGN: Prospective randomized clinical trial. SETTING: The MADDE
      (1989-1994), Illinois site. PARTICIPANTS: A cohort of 412 Medicare-eligible
      caregivers of persons with dementia. MEASUREMENTS: Medicare claims files provided
      data on the number of hospitalizations, hospital bed days, emergency department
      visits, and total Medicare Part A expenditures. RESULTS: After adjustment for
      baseline variables, the caregivers in the treatment group, when compared with
      those in the comparison group, had a lower likelihood of any hospitalization
      during the study period (odds ratio 0.58 (95% confidence interval (CI)=0.35
      0.97), P= .037) and a reduced, but not significant, likelihood of emergency
      department use (odds ratio 0.66 (95% CI=0.40-1.08), P= .095). For those who were
      hospitalized, there were no significant differences between the treatment and
      comparison group caregivers in the number of hospitalizations, hospital length of
      stay, or Medicare payments. CONCLUSION: These results suggest that enhanced
      chronic illness case management directed at persons with dementia and their
      caregivers can reduce the need for acute hospital care.

PMID- 11843992
TI  - Efficacy and safety of ciprofloxacin oral suspension versus trimethoprim
      sulfamethoxazole oral suspension for treatment of older women with acute urinary
      tract infection.
AB  - OBJECTIVES: To compare the efficacy and safety of ciprofloxacin (CIP) oral
      suspension to trimethoprim/sulfamethoxazole (TMP/SMX) oral suspension among older
      women with acute urinary tract infections (UTIs). DESIGN: Prospective,
      randomized, open-label, multicenter study of older women (age 65 and older).
      SETTING: Community and nursing home. PARTICIPANTS: A total of 261 older women
      were evaluable for safety. Of these, 172 (86 community, 86 nursing home) were
      evaluable for clinical and bacteriological efficacy. INTERVENTION: Patients were
      randomized to a 10-day regimen of either CIP (250 mg/5 mL twice daily) or TMP/SMX
      (160/800 mg/20 mL twice daily). MEASUREMENTS: Clinical response 4 to 10 days
      posttherapy. RESULTS: For the efficacy-valid population, posttherapy clinical
      resolution was statistically superior following CIP (97%) versus TMP/SMX (85%)
      (95% CI=2.0-21.3; P= .009). Eradication of pretreatment bacterial isolates
      posttherapy was also higher following CIP (95%) versus TMP/SMX (84%) (95% CI=2.7
      21.3; P= .019). For the intent-to-treat population, posttherapy clinical
      resolution was significantly higher in the CIP group (96%) than in the TMP/SMX
      group (87%) (95% CI=0.2-16.7; P= .025). Safety was assessed in the intent-to
      treat population and the incidence of drug-related adverse events were
      significantly lower following CIP (17%) than following TMP/SMX (27%) (P= .047).
      Premature discontinuation due to these events was also less prevalent with CIP
      than with TMP/SMX (2% vs 11%, respectively) (P= .004). CONCLUSION: CIP suspension
      showed higher clinical success and bacteriological eradication rates than did
      TMP/SMX for both community-based and nursing home-residing older women with acute
      UTIs. Furthermore, CIP suspension was associated with significantly lower rates
      of adverse events and premature discontinuations compared with TMP/SMX
      suspension.

PMID- 11843993
TI  - Outcome of older patients with severe pneumonia predicted by recursive
      partitioning.
AB  - OBJECTIVES: To develop a prognostic model to predict outcome of older patients
      with severe pneumonia requiring mechanical ventilation. DESIGN: A nonconcurrent
      prospective study. SETTING: A 24-bed intensive care unit (ICU) within two
      university-affiliated tertiary care hospitals. PARTICIPANTS: All patients age 75
      and older with severe pneumonia between June 1996 and September 1999 were
      included. Demographic data including activities of daily living (ADL) index score
      before admission, and clinical and laboratory data were collected in the first 24
      hours of admission to the ICU. One hundred four patients (mean age +/- standard
      deviation (SD) 82.3 +/- 5.5 years) met the inclusion criteria. MEASUREMENTS: A
      classification tree was developed using binary recursive partitioning to predict
      hospital discharge. The model was compared with a logistic regression model using
      variables selected by the tree analysis and with the Acute Physiologic and
      Chronic Health Evaluation (APACHE) II. RESULTS: Outcome predictors for the
      classification tree were use of vasopressors, presence of multilobar pneumonia on
      chest radiograph, ratio of blood urea nitrogen to creatinine, Glasgow Coma Scale,
      urine output, and ADL score before admission. The tree achieved a sensitivity of
      83.8% (95% confidence interval (CI) 69.2-92.4) and a specificity of 93.3% (95% CI
      83-98.1). The predictive accuracy as assessed by the area under the curve (c
      index +/- standard error) was significantly higher with the classification tree
      (0.932 +/- 0.03) than with logistic regression and APACHE II, (0.801 +/- 0.028
      and 0.711 +/- 0.049, respectively (P < .05). CONCLUSIONS: The classification tree
      model demonstrated a superior predictive accuracy to that of logistic regression
      and APACHE II. If validated prospectively, the classification tree can be used as
      a tool to assess the outcome of older patients with severe pneumonia requiring
      mechanical ventilation on admission to the ICU. In addition, the classification
      tree can be used to assist healthcare workers in providing a concise summary of
      local outcome experience and prognostic information to patients and their
      surrogates.

PMID- 11843994
TI  - Changes in cognitive function associated with sleep disordered breathing in older
      people.
AB  - OBJECTIVES: Sleep disordered breathing (SDB) is very common in older people and
      is known to be associated with complaints of impaired daily functioning,
      including excessive daytime sleepiness and cognitive impairments. As part of a
      larger study on SDB and aging, it became possible to examine the relationship
      between SDB and cognition in older men and women. DESIGN: A population-based
      longitudinal study. SETTING: In-home interviews and home sleep recordings in the
      greater San Diego area. PARTICIPANTS: Community-dwelling people age 65 and older
      with high risk for SDB were originally studied from 1981 through 1985 and then
      followed every 2 years. Data from the 46 subjects who completed Visit 3 and Visit
      4 are presented. MEASUREMENTS: Subjects were interviewed in the home about their
      sleep and medical condition before each visit. Cognitive function was assessed
      using the Mini-Mental State Examination (MMSE). Daytime sleepiness was based on
      self-report. Objective sleep was recorded in the home and scored for sleep,
      apneas and hypopneas, and oximetry variables. RESULTS: Increases in respiratory
      disturbance index (RDI) (P= .036) and increases in daytime sleepiness (P= .002)
      were associated with decreases in cognitive performance (i.e., increases in
      cognitive impairment). Increases in RDI were also associated with increases in
      daytime sleepiness (P= .012). Change in MMSE scores was therefore regressed onto
      changes in RDI, daytime sleepiness, age, and education, resulting in decreases in
      MMSE scores being associated with increases in daytime sleepiness (P= .019) but
      not with changes in RDI (P= .515). There was no significant relationship between
      changes in oxygen saturation levels and changes in MMSE. CONCLUSIONS: The results
      of this study suggest that declining cognitive function is associated primarily
      with increases in daytime sleepiness. Although cognitive decline was also
      associated with increases in RDI, this association did not hold in the more
      inclusive model which also included variable of SDB, oximetry, sleep and
      subjective report. One theoretical model could suggest that any relationship
      between SDB and cognitive function may be mediated by the effect of SDB on
      daytime sleepiness. These results suggest that older patients suffering from mild
      to moderate SDB may benefit from the treatment of SDB, even if they are not
      markedly hypoxemic.

PMID- 11843995
TI  - Daytime sleepiness is associated with 3-year incident dementia and cognitive
      decline in older Japanese-American men.
AB  - OBJECTIVES: To assess the longitudinal association between sleep disturbances
      (insomnia and daytime sleepiness) and incidence of dementia and cognitive decline
      in older men. DESIGN: Community-based longitudinal cohort study. SETTING: The
      Honolulu-Asia Aging Study of dementia that is linked to the Honolulu Heart
      Program's fourth examination, conducted 1991-1993, and the 3-year follow-up fifth
      examination, conducted 1994-1996. PARTICIPANTS: Two thousand three hundred forty
      six Japanese-American men age 71 to 93 years who screened negative for prevalent
      dementia at baseline and were screened again for dementia incidence in a 3-year
      follow-up examination. MEASUREMENTS: Baseline self-reports of trouble falling
      asleep or early morning awakening (insomnia) and being sleepy during the day
      (daytime sleepiness); Cognitive Abilities Screening Instrument (CASI) scores from
      baseline and followup; clinical diagnosis of incident dementia; and other
      baseline measures including age, years of education, body mass index, depressive
      symptoms, and history of hypertension, heart disease, diabetes mellitus, asthma,
      and use of benzodiazepines. RESULTS: After adjusting for age and other factors,
      persons reporting excessive daytime sleepiness at baseline (8%) were twice as
      likely to be diagnosed with incident dementia than were those not reporting
      daytime sleepiness (odds ratio (OR)=2.19, 95% confidence interval (CI)=1.37-3.50)
      and about 40% more likely to have >or=9 point drop in their CASI score between
      examinations (OR=1.44, 95% CI=1.01-2.08). In contrast, insomnia was not
      associated with cognitive decline or incidence of dementia. CONCLUSIONS: Daytime
      sleepiness in older adults may be an early indicator of decline in cognitive
      functioning and onset of dementia.

PMID- 11843996
TI  - Total body mass, fat mass, fat-free mass, and skeletal muscle in older people:
      cross-sectional differences in 60-year-old persons.
AB  - OBJECTIVES: To evaluate body composition parameters, including fat-free mass
      (FFM), appendicular skeletal muscle mass (ASMM), relative skeletal muscle mass
      (RSM) index, body cell mass (BCM), BCM index, total body potassium (TBK), fat
      mass, percentage fat mass (FM), and their differences between age groups and to
      evaluate the frequency of sarcopenia in healthy older subjects DESIGN: Cross
      sectional, nonrandomized study. SETTING: Outpatient clinic. PARTICIPANTS: Ninety
      one healthy men and 100 healthy women age 60 and older. MEASUREMENTS: FFM, ASMM,
      FM, and percentage fat mass by whole-body dual-energy x-ray absorptiometry; TBK,
      BCM, and TBK/FFM ratio by whole body potassium-40 counter. RESULTS: All lean body
      mass parameters were significantly (P <.05) lower in subjects age 80 and older
      than in those age 70 to 79, except ASMM in women. Mean FFM was 4.2 kg (7.3%)
      lower in men age 80 and older than in those younger than 70 and 2.9 kg (6.8%)
      lower in women age 80 and older than in those younger than 70. The skeletal
      muscle mass, reflected by ASMM, decreased more than FFM. This suggests that
      nonskeletal muscle mass is proportionally preserved during aging. Forty-five
      percent of men and 30% of women were sarcopenic by definition of BCM index and
      11.0% of men and women by definition of RSM index. CONCLUSIONS: Significant age
      related differences exist in body composition of older men and women between age
      60 and 95. The greater decrease in TBK and BCM than the decrease in FFM and
      skeletal muscle mass suggests changing composition of FFM with age. Lack of
      agreement between two independent sarcopenia indexes suggests that further
      refinement in the definition of a sarcopenia index is necessary.

PMID- 11843997
TI  - Ability of fat and fat-free mass percentages to predict functional disability in
      older men and women.
AB  - OBJECTIVES: Previous studies suggest an association between body composition and
      declining functional ability in older people. This study examined the relation
      between functional disability and percentage of fat mass (FM) and percentage of
      fat-free mass (FFM) in older men and women. DESIGN: Cross-sectional and
      prospective. SETTING: Rancho Bernardo, California. PARTICIPANTS: Subjects
      consisted of 1,051 ambulatory, community-dwelling Caucasian men and women, age 55
      to 92, who attended a clinic visit between 1988 and 1992 and a subsequent clinic
      visit between 1992 and 1996. MEASUREMENTS: Measured at both visits, percentage of
      fat mass and percentage of lean body mass were estimated by bioelectric impedance
      analysis and functional disability was ascertained by self-administered
      questionnaire. Functional disability was dichotomized into those having any
      difficulty with a set of tasks versus those having no difficulty with the tasks.
      Two measures of functional disability were used: "lower body" disability,
      consisting of two lower motor tasks (walking 2-3 blocks and climbing up 10
      stairs) and "overall" disability, consisting of nine tasks representing upper and
      lower body function and mobility. RESULTS: Compared with men, women were more
      likely to report both lower body and overall functional disability (P=.001).
      Cross-sectionally, a significant positive association was shown between fat mass
      and overall functional disability and a significant negative association was
      shown between FFM and overall functional disability in both men and women.
      Prospectively, increased percentage of body fat and decreased percentage of FFM
      were significantly associated with decreased functional ability in both women and
      men. All results were adjusted for age, smoking, alcohol use, physical activity,
      current estrogen use, depression, chronic disease, and education. CONCLUSION:
      Increased percentage of fat mass and decreased percentage of FFM are associated
      with greater functional disability in older men and women. Further research is
      needed to assess the relative importance of decreasing fat percentage or
      increasing fat-free percentage to preserve or improve functional ability in older
      people.

PMID- 11843998
TI  - Gait variability in community-dwelling older adults.
AB  - OBJECTIVES: To describe gait variability at usual and fast walking speeds in
      community-dwelling older adults and to describe the effects of increasing gait
      speed on gait variability. DESIGN: Cross-sectional, descriptive study. SETTING:
      The Cardiovascular Health Study at the University of Pittsburgh. PARTICIPANTS:
      Ninety-five community-living older adults, 54 women and 41 men, age 65 and older
      (mean age +/- standard deviation 79.4 +/- 3.37). MEASUREMENTS: Gait measured at
      participant's usual and fast walking speed collected using an instrumented
      walkway. Step-length and step-width variability were determined using the
      coefficient of variation. RESULTS: Step-length variability was greatest in those
      who walked the slowest (r = -0.66, P < .001); step-width variability was smallest
      in those who walked the slowest (r -0.37, P < .001). Individuals who could not
      increase their walking speed (<0.10 m/second) on command had an increase in step
      length variability and a decrease in step-width variability, whereas those who
      could increase their speed (>0.10 m/second) had an increase in step-width
      variability when walking at a faster speed. CONCLUSIONS: Step-length and step
      width variability have opposite associations with gait speed in older adults.
      Improvement in step-length and step-width variability with attempted acceleration
      might be a key factor to examine in future studies of disability risk and
      therapeutic interventions.

PMID- 11843999
TI  - The contribution of foot problems to mobility impairment and falls in community
      dwelling older people.
AB  - OBJECTIVES: To investigate the relationship between foot problems, balance, and
      functional ability in community-dwelling older people and to determine whether
      older people with a history of multiple falls exhibit greater foot impairment
      than those who have not fallen or who have fallen once only. DESIGN: A cross
      sectional, retrospective study. SETTING: Falls and Balance Laboratory, Royal
      North Shore Hospital, Sydney, Australia. PARTICIPANTS: One hundred thirty-five
      community-dwelling men and women age 75 to 93 (mean age +/- standard deviation,
      79.8 +/- 4.1). MEASURES: Foot problem score; postural sway; coordinated
      stability; stair ascent and descent; an alternate stepping test; timed 6-meter
      walk; and tests of vision, sensation, strength, and reaction time. RESULTS:
      Eighty-seven percent of the sample had at least one foot problem. Women had a
      significantly higher foot problem score than did men. The foot problem score was
      significantly associated with performance on the coordinated stability test,
      stair ascent and descent, alternate stepping test, and timed 6-meter walk.
      Multiple regression analyses revealed that the foot problem score was a
      significant independent predictor of performance in the coordinated stability
      test, stair ascent and descent, and the alternate stepping test. Subjects with a
      history of multiple falls had a significantly higher foot problem score than did
      those who had not fallen or who had fallen once only, but the prevalence of
      individual foot conditions or the presence of foot pain did not differ between
      these groups. CONCLUSIONS: Foot problems are common in older people and are
      associated with impaired balance and performance in functional tests.
      Furthermore, older people with a history of multiple falls have greater foot
      impairment than non- or once-only fallers. These findings provide further
      evidence that foot problems are a falls risk factor and suggest that the
      cumulative effect of multiple foot problems is more important in increasing falls
      risk than the presence or absence of individual foot conditions.

PMID- 11844000
TI  - A comparison of longitudinal changes in aerobic fitness in older endurance
      athletes and sedentary men.
AB  - OBJECTIVES: To compare the longitudinal changes in maximal aerobic capacity
      (VO2max) in healthy middle aged and older athletes and sedentary men. DESIGN: A
      cohort study with mean follow-up of 8.7 years (range 4.0-12.8). SETTING:
      Outpatient research at a tertiary hospital. PARTICIPANTS: Forty-two healthy,
      middle aged, and older athletes (initial age 64 +/- 1 year) and 47 healthy
      sedentary men of comparable age recruited for research studies. MEASUREMENTS:
      VO2max during a maximal treadmill test. RESULTS: At baseline, the cross-sectional
      rates of decline in VO2max with age (slope) were virtually identical in the
      athletes and sedentary men (-0.42 versus -0.43 mL x kg(-1) x min(-1) x year(-1)).
      At follow-up, the VO2max had declined by 11.9 +/- 1.1 mL x kg(-1) x min(-1) (22%)
      in the athletes, a crude average rate of -1.4 +/- 0.14 mL x kg(-1)x min(-1) x
      year(-1). By comparison, the VO2max declined by 4.4 +/- 0.6 mL x kg(-1) x min(-1)
      (14%) in the sedentary men, a crude average rate of change of -0.48 +/- 0.07 mL x
      kg(-1) x min(-1) x year(-1). Therefore, the observed absolute rate of
      longitudinal decline in VO2max in the athletes was triple that of the sedentary
      men (P= .001) and significantly greater than the decline predicted by their
      baseline cross-sectional data (P= .001). Post hoc analyses of the longitudinal
      data in the athletes based on the training regimens over the follow-up period
      demonstrated that the seven individuals who continued to train vigorously ("high
      training") had no significant decline in VO2max (0.28% change in VO2max per
      year). By contrast, the VO2max declined by 2.6% per year in the "moderate
      training" group (N=21), 4.6% per year in the "low training" group (N=13), and
      4.7% per year in the two individuals who developed cardiovascular disease.
      CONCLUSION: The longitudinal decline in VO2max in older male endurance athletes
      is highly dependent upon the continued magnitude of the training stimulus. The
      majority of the athletes reduced their training levels over time, resulting in
      longitudinal reductions in VO2max two to three times as large as those predicted
      by cross-sectional analyses or those observed longitudinally in their sedentary
      peers.

PMID- 11844001
TI  - Self-reported utilization of preventive health services by retired employees age
      65 and older.
AB  - OBJECTIVES: Increased utilization of preventive services among the aging has been
      associated with improved health status and decreased medical costs. We sought to
      examine the use of the Health Risk Appraisal (HRA) in benchmarking compliance and
      characterizing those retired employees who met preventive service guidelines.
      DESIGN: A retrospective cohort study of retired employees age 65 and older.
      SETTING: Nation-wide health promotion program offered by General Motors
      Corporation. PARTICIPANTS: 59,670 retired General Motors employees age 65 and
      older who participated in a nationwide mailed HRA health promotion program.
      MEASUREMENTS: Preventive health services compliance was measured using selected
      HRA questions. Gender, HRA participation patterns, overall health risk status,
      medical plan selection and disease status were examined as predictors of
      increased compliance. Multivariate logistic regression models were developed to
      test the relative contributions of participant characteristics to increased
      utilization. RESULTS: The self-reported HRA data indicated that compliance levels
      were higher than national averages. The Healthy People 2000 goals for the
      preventive services studied were met and exceeded (with the exception of tetanus
      immunization). Higher compliance was associated with being male, younger than 70
      years, multiple-year HRA participation, overall low risk status and HMO insurance
      plan selection. CONCLUSION: The results from the HRA indicated that this
      population participated at a higher level than a comparable national sample
      exceeding goals set by Healthy People 2000.

PMID- 11844002
TI  - Chronic benzodiazepine use in nursing homes: effects of federal guidelines,
      resident mix, and nurse staffing.
AB  - OBJECTIVES: To assess the overall prescribing and chronic use of benzodiazepines
      (BZs) in nursing homes before and after implementation of BZ guidelines by the
      Health Care Finance Administration (HCFA). A second aim was to identify facility
      predictors of BZ prescribing and chronic use after guideline implementation.
      DESIGN: Nonexperimental, observational study design. SETTING: Drug use was
      assessed in 16 randomly selected skilled nursing facilities in Wisconsin before
      1990 and again in 1993-1994. PARTICIPANTS: One thousand one hundred eighty-one
      Medicaid-funded residents at baseline and 1,650 Medicaid-funded residents at
      follow-up. MEASUREMENTS: Drug use measures included percentage of residents with
      prescribed BZs and percentage of residents with chronic BZ use (defined as >or=4
      months of continuous use). A 4-month cutoff was used because HCFA guidelines
      consider this length of continuous use to be potentially excessive. Facility
      predictors of drug use included resident demographic and diagnostic mix, size,
      ownership, Medicaid per diem, and nurse staffing. RESULTS: Before 1990, one
      fourth of all residents were prescribed a BZ and nearly one-tenth of all
      residents had chronic BZ use. Federal guidelines had nonsignificant effects on
      these measures; BZ prescribing declined only 3.6% (26.4-22.8%) and chronic use
      declined only 1.3% (9.2-7.9%). Regression results showed that overall prescribing
      at follow-up was higher in facilities with more female residents (beta= .52, P=
      .018) and residents with psychiatric disorders (beta= .41, P= .045). However,
      nurse staffing was the only significant predictor of chronic BZ use. As expected,
      better nurse staffing was associated with lower rates of chronic use (beta= 
      0.46, P= .037). CONCLUSION: Efforts to improve BZ use in nursing homes must
      address the need for better nurse staffing and better assessment and management
      of psychiatric disorders that can trigger BZ prescribing.

PMID- 11844003
TI  - Is serum uric acid level associated with all-cause mortality in high-functioning
      older persons: MacArthur studies of successful aging?
AB  - OBJECTIVES: To explore the effect of serum uric acid level on subsequent all
      cause mortality in high-functioning community-dwelling older persons. It is
      controversial whether high serum uric acid level is a true independent risk
      factor for cardiovascular and total mortality or the association is due to other
      confounding variables. Furthermore, it remains unclear whether the predictive
      value of uric acid level on mortality observed in younger cohorts can be extended
      to older people. DESIGN: Prospective cohort study. SETTING: A sample of community
      dwelling older people. PARTICIPANTS: A cohort of 870 participants from the
      MacArthur Studies of Successful Aging. MEASUREMENTS: Baseline information was
      obtained for serum uric acid level, C-reactive protein (CRP), interleukin-6 (IL
      6), prevalent medical conditions, and health behaviors. Crude and multivariate
      logistic regression analyses were used to examine the association between serum
      uric acid levels and 7-year all-cause mortality, while adjusting for potential
      confounders. RESULTS: In men, the multiply adjusted risk ratios for 7-year total
      mortality were 1.07 (95% CI=0.61-1.88) for the mid tertile of uric acid level and
      1.24 (95% CI=0.70-2.20) for the top tertile. In women, the multiply adjusted risk
      ratios were 0.58 (95% CI=0.29-1.18) and 0.47 (95% CI=0.22-0.99), for the mid and
      top tertiles respectively. CRP and IL-6 were important confounders in the
      relationship between serum uric acid and overall mortality. CONCLUSIONS: High
      serum uric acid level is not independently associated with increased total
      mortality in high-functioning older men and women. When evaluating the
      association between serum uric acid and mortality, the potential confounding
      effect of underlying inflammation and other risk factors must be considered.

PMID- 11844005
TI  - The Vulnerable Elders Survey: a tool for identifying vulnerable older people in
      the community.
AB  - OBJECTIVES: To develop a simple method for identifying community-dwelling
      vulnerable older people, defined as persons age 65 and older at increased risk of
      death or functional decline. To assess whether self-reported diagnoses and
      conditions add predictive ability to a function-based survey. DESIGN: Analysis of
      longitudinal survey data. SETTING: A nationally representative community-based
      survey. PARTICIPANTS: Six thousand two hundred five Medicare beneficiaries age 65
      and older. MEASUREMENTS: Bivariate and multivariate analyses of the Medicare
      Current Beneficiary Survey; development and comparison of scoring systems that
      use age, function, and self-reported diagnoses to predict future death and
      functional decline. RESULTS: A multivariate model using function, self-rated
      health, and age to predict death or functional decline was only slightly improved
      when self-reported diagnoses and conditions were included as predictors and was
      significantly better than a model using age plus self-reported diagnoses alone.
      These analyses provide the basis for a 13-item function-based scoring system that
      considers age, self-rated health, limitation in physical function, and functional
      disabilities. A score of >or=3 targeted 32% of this nationally representative
      sample as vulnerable. This targeted group had 4.2 times the risk of death or
      functional decline over a 2-year period compared with those with scores <3. The
      receiver operating characteristics curve had an area of.78. An alternative
      scoring system that included self-reported diagnoses did not substantially
      improve predictive ability when compared with a function-based scoring system.
      CONCLUSIONS: A function-based targeting system effectively and efficiently
      identifies older people at risk of functional decline and death. Self-reported
      diagnoses and conditions, when added to the system, do not enhance predictive
      ability. The function-based targeting system relies on self-report and is easily
      transported across care settings.

PMID- 11844004
TI  - Zolpidem use and hip fractures in older people.
AB  - OBJECTIVES: The widespread use of sedative-hypnotics in older populations makes
      it imperative to identify hazardous regimens that should be avoided and safer
      regimens that may be used preferentially by older people. Although
      benzodiazepines have been shown to increase fall and fracture risk, zolpidem, a
      nonbenzodiazepine hypnotic, has been advocated as a safer alternative. DESIGN:
      Case-control study of hip fracture cases and controls in 1994. SETTING: All
      subjects were age 65 and older and enrolled in Medicare, and in Medicaid or the
      Pharmaceutical Assistance to the Aged and Disabled program of New Jersey.
      PARTICIPANTS: Cases (n=1,222) were patients who underwent surgical repair of a
      hip fracture. They were frequency-matched to four controls (n=4,888) based on age
      and gender. MEASUREMENTS: Use of sedative-hypnotics and other medications was
      assessed in the 180 days before the index event. We assessed other covariates,
      including demographic, clinical, and healthcare utilization variables in the
      prior 180 days. RESULTS: Zolpidem use was associated with a significant increased
      risk of hip fracture (adjusted odds ratio (AOR) 1.95; 95% confidence interval
      (CI)=1.09-3.51). Other psychotropic medication classes with significantly
      increased risks included benzodiazepines (AOR 1.46; 95% CI=1.21-1.76),
      antipsychotic medications (AOR 1.61; 95% CI=1.29-2.01), and antidepressants (AOR
      1.46; 95% CI=1.22-1.75). In subanalyses, preferential use of zolpidem by subjects
      at greater risk of hip fracture did not appear to explain the apparent risk of
      hip fracture with zolpidem use. CONCLUSION: Use of zolpidem by older people was
      associated with nearly twice the risk of hip fracture, even after controlling for
      possible demographic and clinical confounders. Rather than being a safer
      alternative, zolpidem may be associated with risks that are as great as those
      seen with conventional benzodiazepines in older patients.

PMID- 11844006
TI  - Apathy in Alzheimer's disease.
AB  - Apathy, or loss of motivation, is arguably the most common change in behavior in
      Alzheimer's disease (AD) but is underrecognized. Apathy represents a form of
      executive cognitive dysfunction. Patients with apathy suffer from decreased daily
      function and specific cognitive deficits and rely on families to provide more
      care, which results in increased stress for families. Apathy is one of the
      primary syndromes associated with frontal and subcortical pathology, and apathy
      in AD appears to have multiple neuroanatomical correlates that implicate
      components of frontal subcortical networks. Despite the profound effects of this
      common syndrome, only a few instruments have been designed to specifically assess
      apathy, and these instruments have not been directly compared. Assessment of
      apathy in AD requires clinicians to distinguish loss of motivation from loss of
      ability due to cognitive decline. Although apathy may be misdiagnosed as
      depression because of an overlap in symptoms, current research has shown apathy
      to be a discrete syndrome. Distinguishing apathy from depression has important
      treatment implications, because these disorders respond to different
      interventions. Further research is required to clarify the specific
      neuroanatomical and neuropsychological correlates of apathy and to determine how
      correct diagnosis and treatment of apathy may improve patient functioning and
      ease caregiver burden.

PMID- 11844007
TI  - Advance directive completion rates and end-of-life preferences in Hawaii.
AB  - To estimate rates of advance directive completion, preference for in-home death
      and hospice services at life's end, and support for physician assistance in
      dying, questions were added to two statewide, random-sample telephone surveys-the
      1998 Behavioral Risk Factor Surveillance System (N=2,153) and the 1999 OmniTrak
      health survey (N=700). Data were compared across age, ethnic, and gender groups.
      Overall, 29% of Hawaii residents had a living will, 22% had a healthcare power of
      attorney, 65% said they would prefer a home death, 60% would want hospice
      services, 64% believed a person had a moral right to end his or her life when
      faced with an incurable illness, and 63% felt doctors should be allowed by law to
      end a patient's life if the patient and his or her family requested it. Advance
      directive completion rates increased with age, desire for an in-home death varied
      by gender and ethnicity, and support of assisted-death options varied by
      ethnicity. Despite a large minority population, end-of-life preferences among the
      general population in Hawaii are similar to those of U.S. mainlanders. However,
      age, gender, and ethnic differences exist. Clinicians are encouraged to ask
      patients directly about their preferences as a first step toward improving end-of
      life care.

PMID- 11844008
TI  - Fragmentation of care for frail older people--an international problem.
      Experience from three countries: Israel, Canada, and the United States.
AB  - Cross-national comparisons of healthcare systems can help us to better understand
      them and to offer possible solutions for problems identified within these
      jurisdictions. Because multiple discontinuities present in most healthcare
      systems interfere with the appropriate clinical care of frail older people, we
      were interested in comparing the situation in three countries with markedly
      different healthcare systems. At one end of the spectrum we find Canada, with an
      almost fully socialized system. At the other stands the United States, where
      market forces are allowed the freest rein in any developed nation. Israel offers
      an intermediate model with elements held in common with both the U.S. and
      Canadian systems. Although the problems outlined in this paper can be addressed
      at the "micro" level, it is through an improvement in the structuring and
      organization of national systems of care that the appropriate conditions for the
      care of frail older people can be truly bettered. This international comparison
      offers insights for policy makers in these three states in particular and other
      countries in general.

PMID- 11844009
TI  - Factors relating to the use of physical restraints in geriatric care settings.
AB  - Physical restraints are commonly used on older persons living in geriatric care
      settings. The aim of this study was to investigate the influence of environmental
      and organizational variations and resident and staff characteristics on restraint
      prevalence. In this cross-sectional study of 33 nursing home wards and 12 group
      living units for old persons with dementia in two municipalities in northern
      Sweden, 540 residents (mean age 82) and 529 staff members were evaluated for
      resident and staff characteristics and organizational and environmental
      variables. The proportion of residents with impaired mobility function, the
      number of behavioral disturbances, and nursing staff's attitudes towards use of
      restraints were the strongest discriminators between restraint-free wards and
      wards that used restraints. A classification function analysis showed that these
      three variables could correctly classify the wards as restraint-free, low-use,
      and high-use wards in 63.6% of the cases, with the highest figures for restraint
      free wards (91%). This study has shown that the use of physical restraints is
      strongly connected with residents' functional status and nursing staffs'
      attitudes toward their use.

PMID- 11844010
TI  - Effectiveness of interventions to prevent delirium in hospitalized patients: a
      systemic review.

PMID- 11844011
TI  - An open letter to every medical student who aspires to become a leader in
      academic geriatric medicine.

PMID- 11844012
TI  - Cilazapril-induced SIADH.

PMID- 11844013
TI  - Colonization of skilled-care facility residents with antimicrobial-resistant
      pathogens.

PMID- 11844015
TI  - Hip Fracture Service-an interdisciplinary model of care.

PMID- 11844016
TI  - Serum cholesterol and cerebrospinal fluid amyloid beta protein in Alzheimer's
      disease.

PMID- 11844017
TI  - Folate deficiency and risk of pneumonia in older people.

PMID- 11844018
TI  - Prevalence of oropharyngeal candidiasis in geriatric inpatients.

PMID- 11844019
TI  - Functional effects of dextran sulphate sodium (DSS) treatment on the longitudinal
      muscle of rat distal colon.
AB  - 1. The current study addressed how acute colitis, induced in male Sprague-Dawley
      rats by the administration of dextran sulphate sodium (DSS) in their drinking
      water, may affect some functional properties of the longitudinal muscle layer of
      the distal colon. 2. Dextran sulphate sodium was provided at a concentration of
      3% for 3 or 7 days, or 5% for 7 days, and the rats were thereafter killed.
      Specimens of the distal colon were taken for histology or for organ bath
      experiments. 3. The colitis score increased significantly with increasing dose of
      DSS administered. At 5% concentration, there was sometimes even transmural
      inflammation. Functionally, there was a progressive increase in optimal preload
      (P(o)) for the contractile response to carbachol (1 microM), in relation to the
      severity of the colitis. At 5% DSS, the magnitude of the response to carbachol at
      P(o) was significantly increased compared with control rats. Such an effect could
      not be verified when, instead, K+ (60 mM) was used as a spasmogen. 4. It is
      concluded, that the colitis score increased in severity progressively with
      increasing amounts of DSS administered. The longitudinal muscle layer was
      functionally affected by the inflammation. Thus, there was a progressive increase
      in optimal preload for muscle contraction. Moreover, severe colitis resulted in
      an increase of the contractile response to carbachol, while a significant
      increase in the response to depolarization with K+ could not be found.

PMID- 11844020
TI  - Prostanoid release and constrictor responses to noradrenaline in the rat
      mesenteric vascular bed in non-insulin-dependent diabetes mellitus.
AB  - 1. The administration of streptozotocin (STZ) to 2-day old rats induced a non
      insulin-dependent diabetes mellitus (NIDDM)-like state, with mild hyperglycaemia
      and no alterations in body weight at the adult age. 2. In the isolated and
      perfused mesenteric vascular bed of NIDDM animals, the constrictor responses to
      either noradrenaline (NA) or potassium chloride (KCl) were not modified as
      compared with age-matched non-diabetic controls. 3. The reduction in NA
      contractions induced by the cyclooxygenase inhibitor, 10 microM indomethacin in
      the control group was absent in the NIDDM rats. 4. The increase in the NA-induced
      contractions caused by endothelium removal was suppressed by indomethacin in the
      controls but not in the NIDDM group. 5. The prostanoid release from the
      mesenteric vascular beds of NIDDM rats was markedly reduced as compared with non
      diabetic controls. Noradrenaline increased production of the constrictor
      prostaglandin (PG) F2alpha in control but not in NIDDM rats. 6. In summary, these
      results show that in STZ-induced NIDDM rats, there is an impairment of the
      prostanoid production, as well as a suppression of the role of prostanoids in the
      contractile effects of NA in the mesenteric vascular bed. These alterations are
      more severe than those previously observed in a model of insulin-dependent
      diabetes mellitus (IDDM), in which hyperglycaemia and reduction of body weight
      were more marked. The conclusion is that, in these models of diabetes and in the
      preparation studied, vascular alterations and modifications of glycaemia and body
      weight are not closely related.

PMID- 11844021
TI  - Sensory neuropeptides are not involved in acetaldehyde-induced
      bronchoconstriction in guinea-pigs.
AB  - 1. Alcohol-induced asthma is characterized by worsening of asthmatic symptoms
      after alcohol ingestion. Acetaldehyde, a metabolite of ethanol, is thought to be
      a main factor of alcohol-induced asthma. Although airway sensory nerves are known
      to be activated in asthma, there have been no studies investigating the role of
      tachykinins in the airway response to acetaldehyde. The purpose of the present
      study was to evaluate the involvement of tachykinins on acetaldehyde-induced
      bronchoconstriction in guinea-pigs. 2. After capsaicin desensitization or
      intravenous administration of 10 mg kg(-1) FK224, a NK1 and NK2 dual antagonist,
      airway responses to ascending doses (2.5-20 mg ml(-1)) of inhaled acetaldehyde
      was examined using a modified Konzett-Rossler method in guinea-pigs. 3.
      Inhalation of acetaldehyde induced bronchoconstriction in a dose-dependent
      manner. The FK224 failed to reduce the acetaldehyde-induced bronchoconstriction.
      Pretreatment with capsaicin did not alter the bronchoconstriction induced by
      acetaldehyde at a dose of 2.5-10 mg ml(-1). Pretreatment with capsaicin slightly,
      but significantly, inhibited bronchoconstriction induced by 20 mg ml(-1) of
      acetaldehyde. 4. The present results suggest that tachykinins are not involved in
      acetaldehyde-induced bronchoconstriction in guinea-pigs.

PMID- 11844022
TI  - Regarding the unitary theory of agonist and antagonist action at presynaptic
      adrenoceptors.
AB  - 1. The linkage between potentiation of field stimulation-induced noradrenaline
      release and blockade of the presynaptic inhibitory effect of exogenous
      noradrenaline by a presynaptic antagonist was examined in superfused rabbit aorta
      preparations. 2. Rauwolscine clearly potentiated the release of noradrenaline in
      response to 100 pulses at 2 Hz but reduced the capacity of noradrenaline to
      inhibit transmitter release to a questionable extent, and then only when
      comparisons were made with untreated, rather then to rauwolscine-treated,
      controls. 3. Aortic preparations exposed for 60 min to rauwolscine followed by
      superfusion with antagonist-free Krebs for 60 min retained the potentiation of
      stimulation-induced transmitter release but no antagonism of the noradrenaline
      induced inhibition could be detected at either of two noradrenaline
      concentrations when comparisons were made with rauwolscine treated controls. 4.
      Comparisons of the inhibitory effect of exogenous noradrenaline (1.8 x 10-6 M) on
      transmitter efflux in the presence and absence of rauwolscine pretreatment
      revealed that the antagonist enhanced rather than antagonized the presynaptic
      inhibition by noradrenaline. 5 It is concluded that the unitary hypothesis that
      asserts that antagonist enhancement of transmitter release and its blockade of
      noradrenaline induced inhibition are manifestations of a unitary event are not
      supportable.

PMID- 11844023
TI  - Catecholamines in hyperpnoea-induced airway constriction of guinea pigs.
AB  - 1. We found previously that propranolol augments hyperpnoea-induced
      bronchoconstriction (HIB). This study was performed to investigate the underlying
      mechanism of this aug- menting action of propranolol. 2. In the first series, 45
      young Hartley guinea-pigs were divided into five groups: control; propranolol;
      adrenalectomy; metoprolol and reserpine. Each animal underwent three periods:
      baseline, hyperpnoea, and recovery. For each animal 1 ml of arterial blood was
      sampled during the baseline and recovery periods. 3. Treatments of propranolol,
      metoprolol, and reserpine caused significant decreases in both dynamic
      respiratory compliance (Crs) and forced expiratory volume in 0.1 s (FEV0.1)
      during the baseline period. Hyperpnoea caused slight but not significant
      decreases in Crs, FEV0.1, and maximal expiratory flow at 50% total lung capacity
      (TLC) (V(max50)) during the recovery period in the control group. Propranolol,
      but not other treatments, significantly augmented these decreases (indicating
      HIB). Plasma noradrenaline and adrenaline levels in the reserpine group were not
      detectable. The above treatments or hyperpnoea did not induce any significant
      effect on the plasma noradrenaline level. Plasma adrenaline level of the control
      group was higher than that of either adrenalectomy or reserpine group during the
      baseline and the recovery periods. 4. In the second series, we avoided repeated
      blood samplings. Forty-eight animals were evenly divided into two groups: control
      and propranolol. Each group was again evenly divided into three subgroups:
      baseline; hyperpnoea, and recovery. Five minutes into the recovery period, we
      demonstrated HIB in the control group. In terms of V(max50), this HIB was
      significantly augmented by propranolol. Plasma noradrenaline and adrenaline
      levels, however, were not significantly altered by either hyperpnoea or
      propranolol. 5. Taken together, these data suggest that propranolol-augmented HIB
      has no direct relationship with decreased catecholamine activity.

PMID- 11844024
TI  - Effects of reduced sympathetic activity on myocardial metaiodobenzylguanidine
      (MIBG) washout.
AB  - 1. Increase in myocardial sympathetic activity contributes markedly to the
      pathophysiology of conditions such as congestive heart failure and is also
      associated with myocardial infarction. However, measurement of myocardial
      sympathetic activity in vivo is difficult. 2. The present study assesses the
      effectiveness of metaiodobenzylguanidine (MIBG) imaging to characterize
      modulation of sympathetic activity, as induced by dexmedetomidine, a highly
      specific alpha-2 adrenoceptor agonist. 3. We imaged washout of [125I]-MIBG from
      rabbit heart before and during two consecutive 45-min intravenous infusions of
      dexmedetomidine (10 microg kg(-1) followed by 16 microg kg(-1)) (n=9) or of
      saline (n=9). 4. Heart rate (HR), and mean blood pressure (BP) were measured
      before and at the end of each study period. Plasma noradrenaline (NA) was
      measured before and after study drug infusion. The hearts were then excised and
      biopsied for MIBG tissue concentration [MIBG] (% kg-dose g(-1)). 5. Relative to
      saline controls, dexmedetomidine significantly decreased HR, BP, plasma NA and
      MIBG washout. There was an inverse correlation between MIBG washout and residual
      [MIBG] in the myocardium (r= -0.75, P < 0.01). 6. These data suggest that a
      reduction of sympathetic nervous system activity causes a decrease in myocardial
      MIBG washout in vivo in rabbits, and confirms the usefulness of MIBG scintigraphy
      as a non-invasive tool to measure changes in myocardial sympathetic activity.

PMID- 11844025
TI  - Marginal adaptation of partial crowns cast in pure titanium and in a gold alloy -
      an in vivo study.
AB  - The aim of the present study was to assess in vivo the marginal integrity of
      partial crowns cast in pure titanium and in a gold alloy. For this purpose, two
      groups of 25 molars were prepared for partial crowns and then restored with
      partial crowns cast in Degulor M gold alloy and in pure titanium. At a subsequent
      session, replicas were produced using a special impression-taking technique. The
      scanning electron microscope (SEM) technique was used to perform quantitative
      margin analysis (Tiffmess 1.8 program). The gold alloy partial crowns displayed
      significantly (P < 0.05) more continuous margin (marginal quality A, <50 microm),
      and the titanium partial crowns significantly more marginal quality B (50-100
      microm) and C (>100 microm). The results show that better marginal integrity can
      be achieved with gold alloy than with titanium partial crowns. However, in
      practical terms the difference in marginal quality is only slight, so that the
      use of pure titanium for single-tooth restorations is justified.

PMID- 11844027
TI  - A study of the prevalence and distribution of dentine sensitivity in a population
      of 17-58-year-old serving personnel on an RAF base in the Midlands.
AB  - Previous studies have reported on dentine sensitivity (DS) prevalence in hospital
      and general practice populations. Results from these studies indicate that
      perception and prevalence of DS vary depending on the population. The study aimed
      to determine any major differences in the perception and prevalence of DS in
      subjects in a military training establishment. Questionnaires from 228 subjects
      [188 completed by males, 39 completed by females, with one person not indicating
      their gender of mean age 24.0 years (s.d. 7.16)] were collected and analysed
      using the Statistical Package for the Social Sciences (SPSS). Fifty percent of
      the subjects (n=114) claimed to have DS. Yet approximately 30% of the subjects
      (29.8%, n=68) perceived the condition as a slight problem and approximately 40%
      of the subjects (40.8%, n=93) claimed it was an occasional problem and
      approximately 50% (49.1%, n=112) did not seek treatment. Seventeen subjects
      (7.5%) used a desensitizing paste during periods of discomfort. No clear pattern
      emerged with regard to seasonal variation in DS although 5.7% (n=13) subjects
      considered DS to be more of a problem in winter. Only 7.9% (n=18) reported any
      previous periodontal surgery, consistent with previous studies (12.6 and 15.5%).
      Of those who received regular scaling (27.2%, n=62), only 23 (10.1%) reported any
      discomfort following treatment, which did not last >or=5 days. The results
      indicate that self-reporting of DS was similar to previous reports, although it
      is of fundamental importance that such studies should be supplemented with a
      thorough clinical examination to determine more reliable prevalence data.

PMID- 11844026
TI  - Long-term cytotoxicity of resin-based dental restorative materials.
AB  - Highly filled composites, Ormocers (organically modified ceramics) and 'smart'
      materials have been developed to overcome the polymerization shrinkage problems
      of conventional composite materials. The purpose of the current study was to
      investigate the effect of longer-term (up to 8 weeks) ageing of these resin-based
      dental restorative materials and determine the effect of post-curing on
      cytotoxicity. Twelve discs of each material (Colombus/IDR, Definite/Degussa,
      Ariston pHc/Vivadent) were either light-cured (Lc) or light-cured and post-cured
      (Pc). For cytotoxicity testing, the discs were placed in contact with cell
      culture medium (DMEM) and incubated at 37 degrees C. Extracts from composite
      materials were collected after 24 h and weekly over a time period of 8 weeks.
      Cytotoxicity of the eluates to cultured fibroblasts (Balb/c3T3) were measured by
      the succinic dehydrogenase (SDH) activity (MTT assay) and the results expressed
      in percentage of negative controls (Teflon discs). The results showed that ageing
      significantly influenced the cytotoxicity of the materials. Except for Ariston
      pHc, materials were less cytotoxic after 8 weeks of ageing than they were in
      early intervals and post-curing was not generally useful in reducing
      cytotoxicity. The Ariston pHc was initially moderately toxic, but then become
      highly cytotoxic for 5 weeks before returning to initial levels. The current
      study demonstrated the importance of assessing the cytotoxicity of resin
      composite materials at multiple times.

PMID- 11844028
TI  - Relation between cavity design and marginal adaptation in a machine-milled
      ceramic restorative system.
AB  - The purpose of the current study was to evaluate the influence of inclination of
      the cusp as well as convergence/divergence of the cavity wall on marginal
      adaptation in a machine-milled ceramic restorative system. Sixty inlay specimens
      were prepared from a pre-fabricated feldspathic porcelain (Vitablocs Mark 2) by
      means of a computer integrated manufacturing system (Cerec 2). Specimens were
      divided into 12 groups according to original cavity preparations consisting of
      four inclinations of the cusp (0 degree, 15 degrees, 30 degrees and 45 degrees)
      and three types of cavity form (tapered box, regular box, and undercut box). The
      restorations were cemented with a dual-activated luting agent (Clapearl DC) and
      cut into two halves with a low speed cutting saw, after which adaptation at the
      occlusal surface of each inlay specimen was measured with a microscope. The
      results showed that the inclination of the cusp did not affect adaptation of the
      restorations (P > 0.05), whereas the inlay specimens inserted into undercut
      cavity preparation exhibited significantly poor adaptation as compared with those
      inserted into regular and tapered cavities in two inclinations of the cusp (0
      degree and 15 degrees; P < 0.05). The experimental results suggest that either
      regular or tapered box form cavity preparation is preferable to the undercut box
      form to improve occlusal marginal adaptation of the Cerec 2 ceramic restorative
      system.

PMID- 11844029
TI  - Effect of length and diameter of tapered posts on the retention.
AB  - The force transmission of tapered unthreaded posts along the root has been
      reported to be homogenous but their retentive strength was found to be lower
      compared with those of parallel unthreaded or other kinds of threaded posts. The
      purpose of this in vitro study was to investigate the effect of length and
      diameter on the retentive strength of sandblasted tapered prefabricated titanium
      posts (Erlangen post system). Posts with constant taper angle but with three
      different lengths (9, 12, 15 mm) and apical diameters (0.5, 0.9, 1.1 mm) were
      cemented using zinc phosphate cement into the prepared and roughened post spaces
      of 90 intact anterior teeth. The post retention concerning length and diameter,
      being independent from each other, was measured by a tensile force test. The
      retentive strength was found to be proportional to the length as well as to the
      diameter of the posts. The mean minimum strength (181 +/- 14 N) recorded for the
      thinnest and shortest post was significantly lower than that of mean maximum
      strength (612 +/- 85 N) obtained from those of the thickest and longest post.
      Proportional bond strengths of the posts comprising their surface areas ranged
      between 6.8 and 7.9 N mm(-2) which were not significantly different between any
      group. The retention was effected strongly with the increase in the length
      (approximately 100%) than with the increase in the diameter (approximately 60%).
      Concerning the posts tested in this study, it is concluded that some caution
      should be exercised in the choice of post with appropriate length rather than
      diameter for the tooth concerned.

PMID- 11844030
TI  - Sites of dental erosion are saliva-dependent.
AB  - Acid demineralization of teeth causes occlusal erosion and attrition and
      associated non-carious cervical lesions at sites relatively unprotected by
      saliva. Associations of occlusal pathology and cervical lesions were looked for
      in 450 patients with toothwear, and 174 subjects with cervical lesions were
      identified. Associations of occlusal attrition, or erosion, or no wear, with
      cervical lesions at 72 buccal and lingual sites were recorded from epoxy resin
      replicas of the subjects' dentitions (3241 teeth). Criteria used to discriminate
      occlusal erosion from attrition; and shallow from grooved and wedge-shaped
      cervical lesions were delineated by scanning electron microscopy (SEM). In the
      absence of occlusal pathology, cervical lesions were very rare (<1%). In the
      presence of occlusal pathology, cervical lesions were present in 27.71% of buccal
      sites as opposed to 2.61% of lingual sites. The commonest site of cervical
      lesions was the facial of maxillary incisors (36% of sites). The least common
      site was the lingual aspect of mandibular molars (1.7% of sites). These
      differences may reflect the normal protective role of serous saliva and salivary
      pellicle in a site-specific manner, on the lingual surfaces of mandibular teeth
      particularly, and do not support abfraction as the prime aetiology of cervical
      lesions.

PMID- 11844031
TI  - Human masticatory muscle activity and jaw position under experimental stress.
AB  - The purpose of the present study was to determine whether stress induced a
      consistent pattern of increased electromyographic (EMG) activity in different
      masticatory muscles, and whether stress produced changes in jaw position. Thirty
      five dental students at Taipei Medical College volunteered for this study. Mental
      arithmetic was used to create a stress condition and relaxation instruction was
      used to help relax the subjects. Subjects were asked to evaluate the stress they
      felt under each experimental condition with a visual analogue scale (VAS).
      Surface electrodes were used to monitor the EMG activities of the right masseter,
      right posterior temporalis and suprahyoid muscles. A kinesiograph was used to
      observe the jaw position. Data collected before mental arithmetic or relaxation
      monitored the baseline level. The VAS means were significantly increased during
      the stress condition and significantly decreased following relaxation, compared
      with the baseline. There was also a significant increase in EMG activity of all
      three muscles during mental arithmetic compared with baseline; different patterns
      of increased EMG activity were noticed in the three muscles under a continuous
      stress condition. Under stress, the incidence of tooth contact at intercuspal
      position was also increased.

PMID- 11844032
TI  - Influence of restorative manipulations on the blood perfusion of human marginal
      gingiva as measured by laser Doppler flowmetry.
AB  - Plaque accumulation caused by deficient fixed prosthodontics may evoke unequal
      degrees of gingival inflammation. Clinical investigation was performed to study
      the reaction of marginal gingiva during the course of routine prosthetic
      rehabilitation, e.g. replacement of two two-unit fixed partial dentures for
      aesthetic and functional reasons in a female patient. To characterize the actual
      state of gingival margin we recorded conventional gingivitis indices in
      conjunction with the employment of non-invasive laser Doppler flowmetry (LDF) for
      gingival perfusion measurements. Prior to the treatment procedures (control
      phase) the gingival indices were scored to 1 at all the five measuring points. At
      the end of the rehabilitation those values decreased to zero. A significant
      correlation was found between gingival indices and LDF readings (r=0.37, n=49, P
      < 0.01). Thus, our data suggest that monitoring of gingival blood perfusion by
      LDF may provide valuable information on the healing process of inflamed marginal
      gingiva.

PMID- 11844033
TI  - Occlusal support and head posture.
AB  - In order to examine the relationship between occlusal support and head posture,
      the electromyographic (EMG) activities of the jaw closing muscles and the
      sternocleidomastoid muscle during voluntary maximal clenching (VMC) under several
      conditions of occlusal support in eight healthy dentates were recorded and
      analysed. The head posture was also recorded simultaneously by the
      electromagnetic, 6-degree-of-freedom tracking instrument (POLHMUS Co. 3 SPACE
      WIN*). In the VMC with lateral imbalance of occlusal support, EMG activity of the
      jaw closing muscles and the sternocleidomastoid muscle on the occlusal support
      side was greater than those on the non-occlusal support side, and the neck was
      bent in the direction of the occlusal support side. Moreover, a positive
      correlation was found between the asymmetry of muscle activity (asymmetry index)
      of the sternocleidomastoid muscle and the angle of lateral bending of the neck.
      From these results, it can be said that lateral imbalance of the occlusal support
      could promote imbalance in sternocleidomastoid muscle activity, causing lateral
      bending of the neck. From this study, it is suggested that there is a close
      relationship between occlusal support and head posture.

PMID- 11844034
TI  - Incisal and condylar paths during habitual mouth opening movement of children
      with anterior reverse bite in the primary dentition.
AB  - The purpose of this study was to evaluate whether the path of habitual mouth
      opening was influenced by anterior reverse bite malocclusion in children. Two
      groups of children with the primary dentition were chosen: (i) 10 children with
      anterior reverse bite (reverse bite group) and (ii) 10 with normal occlusion
      (normal occlusion group). Their habitual mouth opening movements were measured by
      an opto-electronic movement-analysing system with 6 d.f. at a sampling rate of
      100 Hz. These movements were projected on the sagittal plane at the incisal and
      condylar points. To characterize the path, we used the angles between the path
      and the horizontal plane. In the initial stage of opening, the incisal path of
      the reverse bite group was displaced more posteriorly from the intercuspal
      position than that of the normal occlusion group. However, as opening continued,
      the direction of the path of the reverse bite group was more anterior than those
      of the normal occlusion group. During the entire opening movement, the condylar
      path of the reverse bite group was flatter than those of the normal occlusion
      group. In conclusion, it was demonstrated that anterior reverse bite in the
      primary dentition clearly affects the paths of habitual opening movements.

PMID- 11844035
TI  - A histomorphometric analysis on bone dynamics in denture supporting tissue under
      continuous pressure.
AB  - The purpose of this study was to investigate bone dynamics under a denture base,
      in relation to the intensity of continuous pressure exerted through it to the
      denture supporting tissue. Two hundred and fifty male rats of Wistar strain were
      divided into five groups, four of which wore experimental dentures to load
      continuous pressure of 0.0, 1.0, 10.0 or 20.0 kPa to the molar region of the hard
      palate. The fifth group was the non-denture-wearing group. Fluorescent labelled
      palatal bone tissue was stained with Villanueva bone stain and was prepared for
      the undecalcified grinding section. In the 0.0 kPa group whose mucosa was covered
      with denture base, although no bone resorption was observed, bone formation was
      inhibited up to 4 weeks after the denture insertion. Bone dynamics in the 1.0 kPa
      group was similar to those in the 0.0 kPa group. In the 10.0 and 20.0 kPa groups,
      bone resorption was observed until 3 and 2 weeks after the denture insertion, and
      the amount of bone resorption (AoBR) was 24 +/- 17 and 35 +/- 21 lm,
      respectively. After bone resorption in these groups, although osteoid formation
      increased earlier than 0.0 kPa group, mineralization showed a similar time course
      with 0.0 kPa group. In conclusion, bone dynamics under a denture base caused by
      continuous pressure exerted through it was revealed to show a time course
      depending on the intensity of the initial pressure. Amount of bone resorption was
      also revealed to correspond to the intensity of the initial pressure. Bone
      formation following bone resorption did not cause equivalent recovery of the bone
      surface level to the level observed in the case without bone resorption.

PMID- 11844036
TI  - The efficacy of intra-articular sodium hyaluronate in patients with reducing
      displaced disc of the temporomandibular joint.
AB  - In this clinical trial, we examined the efficacy of intra-articular hyaluronic
      acid (HA) treatment in 38 patients with reducing displaced disc of the
      temporomandibular joint (TMJ). Subjects received two unilateral upper space
      injections of HA or physiological saline solution with 1 week apart. Efficacy was
      based on the following measurements: pain and sound intensity of the joint
      measured by visual analogue scale (VAS), modified Helkimo's clinical dysfunction
      index and the intensity of joint vibration during opening and closing the mouth
      measured by accelerometers. These measurements were performed before the first
      injection and 1 and 6 months after the last injection. In the treatment group
      (n=19), all measurements improved significantly at month 1 and at month 6
      compared with the baseline (P < 0.01). The same measurements, in the placebo
      group (n=19), did not show any change, except for the pain intensity which
      improved at month 1 and month 6 (P < 0.05). The change in baseline measurements
      of all of the efficacy criteria at month 1 and at month 6 in the treatment group
      was significantly better compared with the change obtained with placebo at the
      same time intervals. This study demonstrates that intra-articular sodium
      hyaluronate (Orthovisc) injection into the TMJ is an effective treatment for a
      reducing displaced disc.

PMID- 11844037
TI  - Environmental damage and occlusal contact area wear of composite restoratives.
AB  - The chemical environment is one aspect of the oral environment, which could have
      an appreciable influence on the in-vivo degradation of composite resins. The
      resin matrix can be softened and fillers constituents can be leached out when
      composites are exposed to certain chemicals/food-simulating liquids (FSLs). A
      reciprocal compression sliding wear device was used to study the effects of the
      chemical environment on occlusal contact area (OCA) wear of four composite
      restoratives (Silux Plus, Z100, Ariston pHc and Surefil). The effects of FSL on
      hardness was also investigated and correlated to wear. Thirty-six hardness/wear
      specimens of each material were made and stored in artificial saliva at 37
      degrees C for 24 h. The specimens were then divided into six groups of six
      specimens and stored in the following FSL for 1 week at 37 degrees C: distilled
      water (W), 0.02 N citric acid (C), 0.02 N lactic acid (L), heptane (H) and 75-25%
      ethanol-water solution (E). Conditioning in artificial saliva (S) was used as
      control. After conditioning, the specimens were wear tested at 20 MPa contact
      stress against SS304 counter-bodies in the respective FSL/artificial saliva up to
      20 000 cycles. Wear depth (lm, n=6) was measured using profilometry. Change in
      hardness (DeltaKHN, Knoop hardness number) was determined by microhardness
      testing pre- and post-conditioning. Results of statistical analyses
      (ANOVA/Scheffe's at significance level 0.05) of wear data were as follows: Silux 
      S, W > L, H, E and C, L > H; Z100 - S, W > all other mediums and E > H; Ariston 
      all other mediums > H; Surefil - W, C > S, L, H, E (> indicates significantly
      more wear). With the exception of Surefil, the greatest wear was observed with
      conditioning and wear testing in water. This ranged from 93.18 +/- 21.96 lm for
      Z100 to 31.43 +/- 2.80 lm for Surefil. For all materials, conditioning in heptane
      resulted in the least wear. This ranged from 8.9 +/- 2.2 microm for Ariston to
      16.5 +/- 5.9 lm for Silux. The effects of the different FSL on OCA wear were
      material dependent. No correlation was observed between DeltaKHN and wear.

PMID- 11844038
TI  - Viability of fibroblasts in cell culture after treatment with different chemical
      retraction agents.
AB  - Prior to fixed prosthodontic impression procedures, temporary horizontal
      retraction of the free gingival tissue should be accomplished apically to the
      preparation finishing line. The mechanical-chemical method using cotton
      retraction cords of various sizes impregnated with various retraction chemicals
      is the most commonly employed retraction technique. Most retraction agents have
      pH values from 0.8 to 0.3, and are therefore hazardous to the cut dentine and
      periodontal tissues. Sympathomimetic vasoconstrictors introduced recently have a
      pH of 5.6, and are free of systemic side-effects. The present study using the dye
      exclusion test, colony forming ability test and colorimetric assay was undertaken
      to evaluate cytotoxic effects of four chemical retraction agents on cultured V-79
      fibroblasts, and the dependence of cytotoxicity on the agent concentration and
      time of exposure. Original concentrations of retraction agents produced stronger
      cytotoxic effects than dilutions of 1:1 and 1:10. The most aggressive agent, 25%
      aluminium chloride, took only 1 min to damage all cell cultures. The proportion
      of cells damaged after 10 min of exposure to tetrahydrozoline was 60%, which was
      significantly less compared with other chemicals tested. With the colony forming
      ability test using retraction agents diluted to 1:10 the greatest number of
      colonies emerged in samples treated with tetrahydrozoline (statistical
      significance: P < 0.01). The colorimetric assay showed equal cytotoxic effects
      for 25% aluminium sulphate and tetrahydrozoline. The colorimetric test used in
      the study has proved an ergonomic, accurate and reliable test for cytotoxicity
      determination.

PMID- 11844039
TI  - Vascular endothelial growth factor in minor salivary glands: effect of ageing.
AB  - Morphological and physiological age changes are described in human salivary
      glands. Vascular endothelial growth factor (VEGF) is neoangiogenic growth factor
      found in normal salivary glands. Considering the neoangiogenic properties of VEGF
      and its important function in inflammation, repair and, probably, in oral mucosa
      homeostasis, the purpose of the present study was to evaluate the effect of
      ageing on the immunolocalization of VEGF in minor salivary glands. Paraffin
      embedded tissue blocks containing normal labial salivary glands were retrieved
      and classified according to the patients' age in two groups (< 20 and > 40-year
      old). The biotin-streptavidin-peroxidase system was used to detect the VEGF
      antigen. The results demonstrated that the mean level of VEGF immunoreaction in
      the young group was not statistically different from the old group when compared
      by the Mann-Whitney U-test (P = 0.54). This may indicate that although salivary
      flow reduction may develop in old patients, some properties of the salivary
      glands may not be affected.

PMID- 11844040
TI  - Investigation of the relationship between oral parafunctions and
      temporomandibular joint dysfunction in Turkish children with mixed and permanent
      dentition.
AB  - The purpose of this study was to investigate the relationship between
      temporomandibular joint (TMJ) dysfunction, bruxism and oral parafunctions in the
      permanent and mixed dentition of Turkish children. Examinations were performed on
      59 children (26 girls and 33 boys) without TMJ dysfunction and 123 children (54
      boys and 69 girls) with TMJ dysfunction in the mixed dentition. In the permanent
      dentition 89 children without TMJ dysfunction (45 girls and 44 boys) and 123
      children with TMJ dysfunction (69 girls and 54 boys) were inducted into this
      study. The children with oral parafunctions (bruxism, nail biting and
      thumb/finger sucking) were determined through questionnaires. The Z-test was used
      for the analyses of the correlation between variables and differences between the
      groups. Generally a significant correlation was found between finger/thumb
      sucking and nail biting and TMJ dysfunction in the mixed dentition and bruxism
      was observed significantly to be associated with TMJ dysfunction in the permanent
      dentition (P < 0.05). The evaluation of the results showed that in the mixed
      dentition groups nail biting was significantly higher in the girls with TMJ
      dysfunction and finger or thumb sucking was significantly higher in the boys with
      TMJ dysfunction compared with those without TMJ dysfunction (P < 0.01). In the
      permanent dentition; bruxism and thumb/finger sucking were significantly higher
      in girls with TMJ dysfunction higher than those without TMJ dysfunction (P <
      0.05). However, thumb/finger sucking was significantly higher in boys without TMJ
      dysfunction than with TMJ dysfunction (P < 0.05). The results of this study
      showed that the association of parafunctions and TMJ dysfunction is present in
      the mixed (thumb/finger sucking and nail biting) and the permanent dentitions
      (bruxism).

PMID- 11844041
TI  - Nurse migration and international recruitment.

PMID- 11844042
TI  - Nursing migration: global treasure hunt or disaster-in-the-making?
AB  - International nurse migration--moving from one country to another in the search
      of employment--is the focus of this article. The majority of member states of the
      World Health Organization report a shortage, maldistribution and misutilisation
      of nurses. International recruitment has been seen as a solution. The negative
      effects of international migration on the 'supplier' countries may be recognised
      today but are not effectively addressed. Nurse migration is motivated by the
      search for professional development, better quality of life and personal safety.
      Pay and learning opportunities continue to be the most frequently reported
      incentives for nurse migration, especially by nurses from less-developed
      countries. Career opportunities were considered key incentives for nurses
      emigrating from high-income countries. Language was reported to be a significant
      barrier. The positive global economic/social/professional development resulting
      from international migration needs to be weighed against a substantial 'brain and
      skills drain' experienced by supplier countries. The vulnerable status of migrant
      nurses is also of concern in certain cases. The focus on short-term solutions as
      opposed to resolving the problem of a worldwide shortage of nurses causes great
      concern. Recent initiatives attempt to curb or channel international recruitment.
      The delicate balance between recognising the right of individual nurses to
      migrate and a collective concern for the health of a nation's population must be
      achieved.

PMID- 11844043
TI  - The globalisation of the nursing workforce: barriers confronting overseas
      qualified nurses in Australia.
AB  - Recent decades have coincided with the rapid globalisation of the nursing
      profession. Within Australia there has been rising dependence on overseas
      qualified nurses (OQNs) to compensate for chronic nurse shortages related to the
      continued exodus of Australian nurses overseas and to emerging opportunities in
      other professions. Between 1983/4 and 1994/5, 30 544 OQNs entered Australia on
      either a permanent or temporary basis, counter-balancing the departure overseas
      of 23 613 locally trained and 6519 migrant nurses (producing a net gain of just
      412 nurses in all). The period 1995/6--1999/2000 saw an additional 11 757
      permanent or long-term OQN arrivals, with nursing currently ranked third target
      profession in Australia's skill migration program, in the context of continuing
      attrition among local nurses. This pattern of reliance on OQNs is a phenomenon
      simultaneously occurring in the UK, the US, Canada and the Middle East --- the
      globalisation of nursing reflecting not merely Western demand but the growing
      agency and participation of women in skilled migration, their desire for improved
      quality of life, enhanced professional opportunity and remuneration, family
      reunion and adventure.

PMID- 11844044
TI  - Postdisciplinarity in mental health-care: an Australian viewpoint.
AB  - This paper outlines some of the powerful forces progressively undermining the
      conceptual and practical foundations upon which the major disciplines have been
      established, and dissolving the boundaries which have traditionally distinguished
      them from each other, particularly those disciplines involved in the healthcare
      enterprise. It discusses some of the implications of these processes for mental
      health nursing, and champions a new cadre of 'postdisciplinary' staff, comprising
      a graduate generic mental healthcare worker and a postgraduate clinical
      specialist. It is argued that such a specialist --- a 'Generic Mental Health
      Worker' --- should be welcomed by all those who want to see improved quality of
      care in mental health services rather than defend a failing system.

PMID- 11844045
TI  - Nursing: a new era for action. A Virginia Henderson memorial lecture.

PMID- 11844046
TI  - Tangled ruptures: discursive changes in Danish psychiatric nursing 1965-75.
AB  - Psychiatric nursing and psychiatric nurses have been referred to in various ways
      over the course of history. These articulations reflect and constitute the ways
      in which nursing is comprehended during specific periods. A rupture in these
      descriptions and conceptions of Danish psychiatric nursing over the period 1965-
      75 is identified using a discourse analytical framework, inspired primarily by
      Foucault. This rupture influenced all aspects of psychiatric nursing: the
      perception of the psychiatric patient, the expertise and knowledge of the nurse
      and the care given by the nurse. The study raises questions about the cultural
      and social changes that occurred prior to the discursive rupture.

PMID- 11844047
TI  - Conserving the vitality of suffering: addressing family constraints to illness
      conversations.
AB  - When persons are confronted with life-threatening or chronic illness, there is
      always a possibility that family members other than the person experiencing the
      illness also suffer as they attempt to manage their own distress. This paper
      describes exemplars from a hermeneutic study that explored therapeutic
      conversations between nurses and families who were living with a member
      experiencing ischaemic heart disease. These conversations uncovered the
      complexity of both individual and family suffering following acute cardiac
      illness events, and called attention to nursing practices that addressed some of
      the ways that family members were constrained from having conversations about the
      illness. When spaces were created for these conversations to occur, possibilities
      for making sense of illness and suffering were revealed as vital. These
      understandings support the efforts of family members to sustain and conserve
      family relationships in the face of illness and suffering, and inform both the
      professional and personal lives of nurses.

PMID- 11844048
TI  - Procedure manuals and textually mediated death.
AB  - The procedure manual as a document represents the practice of nursing care.
      Analysis of such manuals allows us to explore discourses of nursing and the ways
      in which they frame nursing practice. A critical analysis of a hospital procedure
      manual using discourse analysis was undertaken. A specific excerpt concerning
      'Last offices' is used as an example of the institutionalisation of
      organisational values and beliefs as these influence nursing care. 'Last offices'
      directs nursing practices related to the death of a patient, and the laying out
      as preparation for the funeral director or coroner. The analysis shows that
      procedure manuals reproduce hegemonic ideologies of nursing. The analysis also
      shows how nursing practices are constituted by intersecting forces of differing
      locations such as the hospital as an organisation, the healthcare system and the
      wider society within which these function.

PMID- 11844049
TI  - Glomerular expression of alpha-smooth muscle actin reflects disease activity of
      IgA nephropathy.
AB  - To elucidate the relationship between histological disease states and
      clinicopathological features in immunoglobulin A nephropathy (IgAN), 90 needle
      biopsy specimens diagnosed as IgAN were analyzed. The specimens were divided into
      four groups according to histological grade and stage index. Immunohistochemical
      features of alpha-smooth muscle actin (alpha-SMA), macrophages positive for
      myeloid/histiocyte antigen (MAC387), and expression of type I, III and IV
      collagens were all examined. Glomerular expression scores of alpha-SMA and the
      degree of intraglomerular macrophage infiltration were highest in the active and
      non-sclerotic groups. Type I and IV collagens were significantly more abundant in
      the sclerotic groups than in the active groups. Type III collagen was strongly
      expressed in both the active and sclerotic groups. Double immunolabeling of alpha
      SMA and intercellular adhesion molecule (ICAM)-1 revealed that ICAM-1 was
      expressed around the alpha-SMA-positive mesangial area. In multivariate analysis,
      the glomerular expression score of alpha-SMA was mostly correlated with
      histological grading in the 10 clinicopathological parameters. Type IV collagen
      score was mostly correlated with histological staging. These results suggest that
      glomerular alpha-SMA expression reflects the histological activity of IgAN.
      Immunohistological staining of alpha-SMA is valuable to estimate the degree of
      disease activity in IgAN.

PMID- 11844050
TI  - Classic type of Kaposi's sarcoma and human herpesvirus 8 infection in Xinjiang,
      China.
AB  - We report 17 cases of the classic type of Kaposi's sarcoma in Xinjiang, which is
      located in the north-western area of China surrounded by Mongolia in the east,
      Russia in the north and Kazakhstan in the west. Fifteen of the patients were of
      the Uygur people. All patients were male and did not have acquired
      immunodeficiency syndrome. Most of the lesions were found in the lower and/or
      upper extremities, with 16 patients showing multiple lesions. Immunohistochemical
      examination of the lesions revealed that human herpesvirus 8 (HHV-8)-encoded
      latency-associated nuclear antigen was expressed in the nuclei of spindle-shaped
      tumor cells. HHV-8 DNA was detected by polymerase chain reaction in all seven
      cases examined. Phylogenetic tree analysis revealed that DNA sequences of the HHV
      8-encoded K1 gene in the seven Kaposi's sarcoma cases were classified as subtype
      C that was common in the Mediterranean, the Middle East and East Asian countries.
      In addition, using immunofluorescence we investigated the seroprevalence of HHV-8
      in 73 Uygur patients with diseases other than Kaposi's sarcoma. Surprisingly, the
      serological study revealed that 34 of the patients (46.6%) were positive for
      antibodies against HHV-8, suggesting that HHV-8 infection is widespread in
      Xinjiang area. The occurrence of the classic type of Kaposi's sarcoma with a high
      seropositivity rate implies that Xinjiang is the most endemic area for HHV-8
      infection in the world known to date. Considering that Xinjiang is located at the
      middle point of the Silk Road that used to extend from Rome to China, these data
      imply that the virus may have been in circulation in this area due to the
      migration of the people via the Silk Road.

PMID- 11844051
TI  - Expression of MUC1 and MUC2 mucins and relationship with cell proliferative
      activity in human colorectal neoplasia.
AB  - Our previous studies on MUC1 and MUC2 mucin expression in various human neoplasms
      have found that MUC1 expression is related with a poor outcome whereas MUC2
      expression is related with a favorable outcome. In the present study, we examined
      the alteration of MUC1 and MUC2 antigens on malignant transformation of
      colorectal mucosa, and also its relationship with cell proliferative activity (Ki
      67 labeling index) of neoplastic epithelial cells in 200 adenomas and 58
      carcinomas. In the 200 adenomas, we analyzed a total of 400 adenomatous lesions
      (mild dysplasia, 200 lesions; moderate dysplasia, 153 lesions; severe dysplasia,
      47 lesions). MUC1 was expressed in carcinomas (24%) and adenomas with severe
      dysplasia (4%), but was not expressed in adenomas with mild or moderate
      dysplasia. MUC2 was expressed in a significantly greater number of adenomas with
      mild dysplasia (72%) than in adenomas with moderate dysplasia (45%) or severe
      dysplasia (47%), as well as in the carcinomas (38%; P < 0.0001). The Ki-67
      labeling index was significantly lower in the MUC2-positive cases than in the
      MUC2-negative cases in the adenomas with mild dysplasia (13.6 vs 24.2%; P <
      0.0001) or moderate dysplasia (25.7 vs 44.4%; P < 0.0001), and in the carcinomas
      (32.5 vs 48.4%; P < 0.05). In conclusion, the data from our study indicate that
      increased MUC1 expression and reduced MUC2 expression may be related to malignant
      transformation of colorectal neoplasia. We also demonstrated that decreased MUC2
      expression, which is correlated with increased Ki-67 labeling, may play an
      important role in the progression of colorectal adenomatous change.

PMID- 11844052
TI  - Histo-topographic distribution of acute inflammation of the human umbilical cord.
AB  - Acute inflammation of the umbilical cord, acute funisitis, is a sign of fetal
      inflammatory response, and the clinicopathological need for its identification is
      increasing. This study was conducted in order to describe the topographic
      distribution of acute funisitis, and thereby to provide more information on the
      intrinsic nature of acute funisitis and find a better way of pathologically
      examining the umbilical cord. A total of 10 umbilical cords affected by acute
      funisitis were histopathologically examined throughout their entire lengths at 1
      mm intervals. Pathological examination was done to characterize the extent of the
      funisitis, the involvement of the vein (phlebitis) or of one or both arteries
      (arteritis), and the presence of inflammation in Wharton's jelly. Umbilical cord
      plasma interleukin (IL)-6 was measured by specific immunoassay to assess whether
      or not the severity of acute funisitis correlates with fetal cytokine response.
      It would appear that the inflammatory reaction begins as a discrete, multifocal
      process which eventually becomes contiguous as the inflammatory reaction
      proceeds. Umbilical cord plasma IL-6 concentrations tended to correlate with the
      extent of umbilical cord inflammation. The initial phase of acute funisitis
      involves discrete and multiple foci along the length of the umbilical cord.
      Moreover, the extent of acute funisitis reflects the severity of systemic fetal
      cytokine response. Therefore, adequate sampling using multiple sections would
      facilitate the identification of acute funisitis. We propose a standard sampling
      procedure taking one section from each third of the umbilical cord.

PMID- 11844053
TI  - Phyllodes tumors of the breast: correlation of nucleolar organizer regions with
      histopathological malignancy grading, flow cytometric DNA analysis and clinical
      outcome.
AB  - To examine whether nucleolar organizer regions detected by argyrophilia (Ag-NOR
      counts) can be used as a prognostic indicator in phyllodes tumors of the breast,
      and to compare its usefulness with that of DNA flow cytometric analysis, 28 cases
      of breast phyllodes tumors (including 15 benign, two borderline and 11 malignant
      tumors) were subjected to Ag-NOR staining and counting as well as DNA flow
      cytometric analysis. S-phase fraction and DNA ploidy analysis showed useful
      trends for improving outcome predictions in malignant phyllodes tumors. However,
      high Ag-NOR counts were significant in predicting survival status (P = 0.013) and
      reached near statistical significance in predicting survival times (P = 0.07). In
      predicting survival status, results for Ag-NOR counts were significantly better
      than those for ploidy analysis (P = 0.02) and S-phase fraction (P < 0.01). Only S
      phase fraction was significantly predictive of survival times (P = 0.025). It is
      concluded that Ag-NOR counts and DNA flow cytometric analysis, easily performed
      using paraffin sections, give information that can improve predictions made by
      histopathological classification. Ag-NOR counts are significant in predicting
      survival in the presence of histopathological features of malignancy.

PMID- 11844054
TI  - Primary neuroendocrine carcinoma of the liver: an autopsy case.
AB  - An autopsy case of primary hepatic neuroendocrine carcinoma is described. A 72
      year-old man had a large tumor mass measuring 22 cm in its greatest diameter and
      localized to the right, left and caudal lobes of the non-cirrhotic liver.
      Microscopically, the tumor was composed of middle-sized pleomorphic cells
      organized in ribbons or trabeculae, with scanty intersecting fibrous septae.
      Immunohistochemically, the tumor cells were positive for multikeratin C11,
      chromogranin A and synaptophysin. The patient also had metastases in the bone
      marrow. No alternative primary source of endocrine tumor was detected. The
      patient died 4 days after presentation.

PMID- 11844056
TI  - Pleomorphic adenoma of the parotid gland with extensive bone formation.
AB  - We report an unusual case of pleomorphic adenoma with extensive bone formation,
      occurring in the parotid gland of a 58-year-old Japanese man. The tumor was a
      well-circumscribed mass that measured 20 x 20 x 15 mm and contained extensive
      bone formation. Histologically, most of the tumor was composed of bone and
      chondroid tissues. The bone formation with a marrow-like structure occupied half
      the volume of the tumor. The chondroid tissues merged continuously into bone
      tissues. The bone tissue seemed to be formed within areas of chondral tissue by a
      process of enchondral ossification. Except for the unusual amount of large bone
      formation, the tumor showed histology of pleomorphic adenoma, particularly at the
      periphery of the tumor. These histological findings suggest the possibility of
      extensive enchondral ossification in pleomorphic adenoma.

PMID- 11844055
TI  - Pancreatic granular cell tumor combined with carcinoma in situ.
AB  - A 58-year-old man was treated for a granular cell tumor (GCT) of the pancreas; a
      very rarely occurring tumor. The patient, who had been followed for 6 years due
      to alcoholic hepatitis, chronic pancreatitis and elevated carcinoembryonic
      antigen (CEA) levels from smoking, was admitted to our hospital for evaluation of
      back pain, diarrhea and constipation. The patient was diagnosed as having
      pancreatic head cancer using clinical imaging studies, and a pylorus-preserving
      pancreatico-duodenectomy was done. In the resected specimen, a white tumor
      measuring 13 mm in diameter was observed at the pancreatic head, and there was
      marked fibrous change surrounding the tumor. The microscopic appearance of the
      pancreas showed atrophy of acinar cells, fibrosis, and dilatation of the main
      pancreatic duct (MPD). Within the tumor were oval cells with low-grade atypia and
      an increased number of diffuse eosinophilic granules. Neither mitosis nor
      invasive findings were observed. Periodic acid-Schiff staining and
      immunohistochemical staining for the S-100 protein were positive, thus the tumor
      was diagnosed as a benign GCT. In addition, carcinoma in situ was found at the
      dilated MPD. Therefore, this patient was diagnosed as having GCT with carcinoma
      in situ of the pancreas. To the best of our knowledge, this is only the fourth
      case of GCT of the pancreas to be reported.

PMID- 11844058
TI  - Ciliated epithelia in the urethra: case report and literature review.
AB  - The presence of ciliated epithelial cells in the urethra has not been well
      recognized. Only two reports in the literature, both of which used scanning
      microscopy studies, have described this phenomenon. In this report, we illustrate
      the presence of scattered, ciliated epithelial cells in penile urethral biopsy
      specimens from a 38-year-old man with a history of bladder calculi and hematuria,
      by both light and transmission electron microscopy studies. The cilia in the
      urethra showed typical light microscopic and ultrastructural features of those
      seen in other organs. These ciliated cells are present in association with
      urothelial papilloma, condyloma acuminatum and acute inflammation of the urethra.
      These findings suggest that ciliated cells in the penile 0 urethra might be a
      consequence of metaplastic change of the urothelium, secondary to local
      stimulation or irritation.

PMID- 11844057
TI  - Myxoid adrenal cortical adenoma.
AB  - Myxoid adrenal cortical adenoma is a rare tumor and, to our knowledge, only 16
      cases have been reported. We present the case of a 56-year-old Japanese man who
      was admitted to hospital because of a right adrenal mass that was discovered
      during a routine physical examination. The resected mass was well circumscribed
      and contained canary yellow multinodular regions that were surrounded by a brown
      gelatinous region. Histologically, the multinodular regions resembled a
      conventional adrenal cortical adenoma, being composed of solid aggregates of
      large clear or eosinophilic cells. In the gelatinous region, anastomosing small
      eosinophilic or vesicular cells were visible within a myxoid stroma that
      contained large amounts of acidic mucopolysaccharides. Light-microscopic findings
      were consistent with a diagnosis of adenoma. Immunohistochemical staining
      revealed that a small number of tumor cells were positive for vimentin, and the
      MIB-1 labeling index was less than 1%. Flow cytometry demonstrated that cells
      were diploid. At the ultrastructural level, many fat droplets were found in the
      large clear cells in the multinodular regions. Small eosinophilic cells in the
      myxoid region contained many mitochondria but few fat droplets. There were no
      findings suggestive of malignancy. Although the adrenal cortex might have the
      potential to produce connective tissue-type mucin as a consequence of its
      mesodermal origin, the mechanism of production of acidic mucopolysaccharides in a
      myxoid adrenal cortical tumor remains to be clarified.

PMID- 11844059
TI  - Uterine angiomyolipoma: case report and review of the literature.
AB  - Extrarenal angiomyolipomas (AML) have been reported at various anatomical sites,
      but infrequently in the gynecological region. In the uterus, only a few cases
      have been described. We describe a uterine angiomyolipoma occurring in a 40-year
      old woman without evidence of tuberous sclerosis. The tumor arose on the right
      wall of the uterine body and was partially cystic, and it was associated with
      marked degeneration. It was composed of mature adipose tissue, anomalous blood
      vessels and non-vascular smooth muscle cells. Immunohistochemistry revealed that
      non- vascular smooth muscle cells were positive for alpha-smooth muscle actin
      (alpha-SMA), desmin, vimentin, antihuman muscle actin (HHF35) and progesterone
      receptor (PR), and negative for cytokeratin, antihuman melanoma (HMB45), CD34, S
      100 and estrogen receptor (ER). It is of particular interest that non-vascular
      smooth muscle cells were negative for HMB45, in contrast to renal and other
      extrarenal AML in which HMB45 immunoreactivity has been demonstrated in these
      cells.

PMID- 11844060
TI  - Compound melanocytic nevus arising in a mature cystic teratoma of the ovary.
AB  - A 28-year-old woman complained of irregular menstruation. Abdominal ultrasound
      and magnetic resonance imaging (MRI) examinations revealed a cystic tumor in the
      left ovary. A histological examination of the resected ovary revealed that the
      lesion was a mature cystic teratoma. In this tumor, components such as skin with
      appendages, a thyroid gland, mucosa of the digestive tract and a submandibular
      gland were observed. Interestingly, compound melanocytic nevus was also present
      in the skin component. To the best of our knowledge, this is the sixth reported
      case of nevus arising in a mature cystic teratoma of the ovary. Despite the
      extreme rarity of such a lesion, pathologists should recognize the possibility of
      such lesions occurring in ovarian teratoma.

PMID- 11844061
TI  - Solitary fibrous tumor in the mental region.
AB  - Solitary fibrous tumor (SFT) is a rare, benign, soft tissue tumor that most
      commonly occurs in the pleura; however, it has recently been described in other
      sites of the body. To date, eight examples of oral SFT have been reported. This
      paper is a description of the first case of an SFT occurring as a soft tissue
      tumor in the mental region. Histologically, the tumor was composed predominantly
      of rather uniform spindle-shaped fibroblastic cells arranged in vague fascicles
      or in a haphazard fashion, intermingled with abundant collagen fibers.
      Immunohistochemically, the tumor cells were positive for CD34 and vimentin, and
      weakly positive for muscle actin and alpha-smooth muscle actin. The diagnosis of
      SFT may be difficult as this tumor shares a number of histological features with
      other soft tissue tumors. Awareness of its occurrence in the oral cavity is
      important so that confusion with other spindle cell neoplasms can be avoided.

PMID- 11844062
TI  - Abnormal IgG galactosylation in MRL-lpr/lpr mice: pathogenic role in the
      development of arthritis.
AB  - MRL-lpr/lpr (MRL/lpr) mice spontaneously develop arthritis by an increase in the
      incidence of agalactosylated oligosaccharides in serum IgG, similar to rheumatoid
      arthritis patients. However, whether this association has a pathogenic
      significance is still unknown. In this study, we analyzed the oligosaccharide
      structure of serum IgG in various MRL mice with or without arthritis, to clarify
      the relationship between the oligosaccharide abnormality and the development of
      arthritis. The level of agalactosylation in serum IgG was comparable in both
      arthritis-free MRL/lpr and MRL-+/+ (MRL/+) mice at 6 weeks of age. In contrast,
      the incidence of IgG lacking galactose markedly increased in MRL/lpr mice at 6
      months of age (the age at which arthritis occurred), compared with that from age
      matched MRL/+ mice without arthritis. However, the proportion of agalactosylated
      IgG increased similarly in anti-CD4 monoclonal antibody-treated MRL/lpr mice at 6
      months of age, despite the absence of the development of arthritis, because of
      depletion of CD4+ T cells. These results suggest that the abnormality in IgG
      galactosylation of MRL/lpr mice developed in an age-dependent manner, but it did
      so independently of CD4+ T cell-dependent B-cell activation and is not a
      consequence of the development of arthritis.

PMID- 11844063
TI  - Histological study of PIVKA-II expression in hepatocellular carcinoma and
      adenomatous hyperplasia.
AB  - Although serum concentration of protein induced vitamin K absence or antagonist
      II (PIVKA-II) has been widely used for diagnosing hepatocellular carcinoma (HCC),
      little information is available concerning tissue PIVKA-II as an
      immunohistochemical marker for liver histology. In this study, we examined the
      expression of PIVKA-II in precancerous nodules (adenomatous hyperplasia) and
      various differentiation grades of HCC by immunohistochemical study using the
      monoclonal anti-PIVKA-II antibody (MU-3). We examined the relationship between
      tissue PIVKA-II staining and serum PIVKA-II level, tumor histology and tumor
      size. PIVKA-II was mainly detected in the cytoplasm of the HCC cells. The
      positive rates of PIVKA-II were as follows: adenomatous hyperplasia (AH), 0%
      (0/9); well-differentiated HCC, 65% (15/23); moderately differentiated HCC, 85%
      (22/26); poorly differentiated HCC, 54% (7/13). The expression of tissue PIVKA-II
      staining in moderately differentiated HCC was significantly higher than in well-
      or poorly differentiated HCC, whereas the serum PIVKA-II level in poorly
      differentiated HCC was higher than well- or moderately differentiated HCC. There
      was no relationship between the expression of PIVKA-II in cancer tissues and
      serum levels of PIVKA-II. Immunohistochemical studies revealed that PIVKA-II was
      expressed even in small-sized or well-differentiated HCC cells, but expression
      was not detected in AH. It was concluded that PIVKA-II is a useful
      immunohistochemical marker, even in small-sized or well-differentiated HCC.

PMID- 11844064
TI  - E-cadherin, alpha-catenin and beta-catenin in biliary atresia: correlation with
      apoptosis and cell cycle.
AB  - Biliary atresia (BA) is the most common cause of obstructive jaundice in infancy.
      Although the etiology of BA remains unknown, the ductal plate malformation has
      been considered to play an important role in the development of BA. Cell-cell
      adhesion has long been recognized as one of the most important processes in
      organogenesis. E-cadherin is involved in cell-cell adhesion, together with the
      catenins. Abnormalities of E-cadherin and associated catenins have not been
      examined in detail in the liver with BA. We therefore examined immunolocalization
      of E-cadherin and alpha- and beta-catenins in the BA liver (n = 45) and compared
      the findings with those in non-BA (n = 11) and fetal liver (n = 21). We
      semiquantitatively evaluated the findings using H score, which were generated
      according to the percentage of immunopositive cells and their immunointensity. We
      also examined mRNA localization of E-cadherin using mRNA in situ hybridization.
      We then studied the correlation of E-cadherin immunoreactivity with apoptotic
      cells, and cyclin-dependent kinase inhibitor p27Kip1 immunolocalization of bile
      duct cells in BA liver (n = 10) and fetal liver (n = 10). In fetal liver, H score
      of E-cadherin, but not of alpha- and beta-catenins, was significantly lower in
      the remodeling stage than in the ductal plate (P = 0.0034) and remodeled stages
      (P = 0.0024). In addition, the H score of E-cadherin, but not alpha- and beta
      catenin, in bile duct cells was significantly lower in BA liver than in non-BA
      liver (P = 0.0132). E-cadherin mRNA hybridization signals were relatively
      conserved in bile duct cells of BA liver, but decreased in remodeling ductal
      plate cells of fetal liver. An inverse correlation was detected between the H
      score of E-cadherin and the TUNEL labeling index (LI) in both fetal and BA liver.
      In contrast, a positive correlation was detected between the H score of E
      cadherin and p27 LI in both fetal and BA liver. These findings suggest that
      impaired expression of E-cadherin in bile ducts may play an important role in the
      biological features of BA, possibly associated with cell cycle and apoptosis.

PMID- 11844066
TI  - The values of intratumoral mast cell count and Ki-67 immunoreactivity index in
      differential diagnosis of uterine smooth muscle neoplasms.
AB  - In this study, the role of the count of intratumoral mast cells was examined and
      compared with the proliferative activity exhibited by Ki-67 indices in the
      differential diagnosis of uterine smooth muscle tumors. Sixteen cases of
      leiomyosarcoma, nine cases of atypical leiomyoma and 16 cases of ordinary
      leiomyoma were included. The pathological features of the cases were determined
      by reviewing the archive materials including the patient records and hematoxylin
      eosin-stained sections. Toluidine blue stain was used to highlight the
      intratumoral mast cells and they were counted in at least 40 high power fields. A
      standard streptavidin-biotin method was applied to the sections to highlight the
      Ki-67 immunoreactive tumor cell nuclei. These proliferative cells were counted in
      at least 10 high-power fields. Atypical leiomyomas tended to have a higher
      quantity of intratumoral mast cells than leiomyosarcomas and ordinary leiomyomas
      (P = 0.027 and P = 0.021, respectively). Leiomyosarcomas tended to have higher Ki
      67 immunoreactivity rates than atypical leiomyomas, although the difference was
      not statistically significant (P = 0.82). We concluded that the quantity of
      intratumoral mast cells is useful in the differential diagnosis between
      leiomyosarcomas and atypical leiomyomas, while the cell proliferation rate
      expressed by Ki-67 immunoreactivity has a limited value.

PMID- 11844065
TI  - Mechanism of intramedullary high intensity area on T2-weighted magnetic resonance
      imaging in osteoid osteoma: a possible role of COX-2 expression.
AB  - To study the mechanism and pathophysiology of the development of intramedullary
      high intensity areas on T2-weighted magnetic resonance images (MRI) in cases of
      osteoid osteoma, we examined the expression of cyclooxygenase-2 (COX-2) in the
      nidus and surrounding bone tissues. In all six cases showing a marked
      intramedullary high intensity area adjacent to the nidus before surgery,
      neoplastic osteoblasts inside the nidus showed strong and diffuse COX-2
      immunoreactivity. On the other hand, the osteoblasts rimming the surrounding
      reactive bone were COX-2 negative. In two cases examined by reverse transcription
      polymerase chain reaction (RT-PCR), COX-2 mRNA was detected in abundance in the
      nidus. Histologically, vascular dilatation together with intramedullary edema was
      observed in all cases, which was probably reflected as a high intensity area on
      T2-weighted MRI. From our study, a high level of COX-2 expression in neoplastic
      osteoblasts in the nidus of osteoid osteomas may cause the secondary changes
      depicted by MRI.

PMID- 11844067
TI  - Olfactory neuroblastoma with epithelial and endocrine differentiation transformed
      into ganglioneuroma after chemoradiotherapy.
AB  - We report a 56-year-old man in whom an olfactory neuroblastoma with epithelial
      and endocrine differentiation transformed into a mature ganglioneuroma after
      chemoradiotherapy. The tumor arising from the sphenoidal and maxillary sinuses
      showed rapid growth into the frontal lobe and metastasis to the cervical lymph
      nodes. The patient showed signs of a syndrome of inappropriate secretion of
      antidiuretic hormone (SIADH). A radical craniofacial resection of the primary
      tumor was performed after 16 Gy of local irradiation and systemic chemotherapy.
      Three months after the operation, the patient died of mediastinal metastasis. The
      biopsy before chemoradiotherapy showed a neuroblastoma with Homer-Wright
      rosettes, fibrillary matrix, Flexner-Wintersteiner rosettes and antidiuretic
      hormone production. After chemoradiotherapy, the histology changed to that of a
      ganglioneuroma consisting of large ganglion cells and Schwann cells without
      immature neuroblastoma components. Although transformation to ganglioneuroma in
      an adrenal neuroblastoma is common, an olfactory neuroblastoma showing
      ganglioneuronal maturation after chemoradiotherapy has not been reported. The
      pluripotent progenitor cells of the olfactory neurons may be the origin and their
      existence explains why various neoplasms with neuronal and epithelial
      differentiation arise from the olfactory mucosa.

PMID- 11844068
TI  - Metastasis of renal cell carcinoma to central nervous system hemangioblastoma in
      two patients with von Hippel-Lindau disease.
AB  - Here we report tumor-to-tumor metastases identified in two patients with von
      Hippel-Lindau (VHL) disease. The first patient had bilateral renal carcinomas and
      multiple cerebellar hemangioblastomas, and the second patient had a renal
      carcinoma and multiple hemangioblastomas in the retina, cerebellum and spinal
      cord. A cerebellar lesion from the first patient and a spinal lesion from the
      second patient contained two distinct components. The inner part of these tumors
      consisted of a nested mass of polygonal clear cells that expressed cytokeratin
      and epithelial membrane antigen, while the outer part of the tumors showed
      proliferation of capillaries and intervening foamy stromal cells that were
      negative for cytokeratin and epithelial membrane antigen. The tumors were thus
      considered to be hemangioblastomas complicated by metastatic lesions of renal
      cell carcinoma of clear cell type. These cases indicate that tumor-to-tumor
      metastasis should be considered when hemangioblastoma contains a clear cell
      carcinoma component in the setting of VHL disease, and that immunohistochemical
      staining for cytokeratin and epithelial membrane antigen is useful for the
      diagnosis.

PMID- 11844069
TI  - Low-grade renal cell carcinoma arising from the lower nephron: a case report with
      immunohistochemical, histochemical and ultrastructural studies.
AB  - Most renal cell carcinomas (RCC) are composed of clear cells with sinusoid-like
      vasculatures and originate from the proximal tubule. On the other hand,
      collecting duct carcinoma (CDC) and chromophobe RCC are thought to originate from
      the lower nephron. In the present study, we present a case of unusual RCC. The
      patient was a 68-year-old Japanese woman who had developed general fatigue with
      hematuria. Computed tomography revealed a left renal tumor suggesting sarcoma.
      The resected tumor was located in the renal parenchyma, measuring 12 x 10 x 8 cm
      in size. Histologically, the tumor consisted principally of cuboidal cells
      forming parallel or radiating arrays, continuous with the spindle-shaped cells.
      Most parts of the tumor showed hemorrhagic necrosis. Immunohistochemically, tumor
      cells were positive for high molecular weight cytokeratins, vinculin, vimentin,
      CD15 and epithelial membrane antigen, and showed affinities with some kinds of
      lectins. N- and E-cadherins and beta-catenin were diffusely positive in tumor
      cells. Nuclear positivity for Ki-67 and p53 protein were approximately 2.0 and
      1.7%, respectively. Considering its morphological and histochemical natures, this
      tumor is considered to have originated from the lower nephron, which is unique
      for a tumor of low-grade malignancy.

PMID- 11844070
TI  - Double cancer consisting of adenosquamous and hepatocellular carcinomas of the
      liver.
AB  - A very rare case of a double cancer consisting of adenosquamous and
      hepatocellular carcinomas of the liver in a 65-year-old-man is discussed. The
      patient was hospitalized with epigastralgia in May 1997. Abdominal computed axial
      tomography revealed a tumor located in the left lobe of the liver and a left
      hepatic lobectomy was performed. The tumor recurred several months after surgery
      and the patient died on 4 June 1999. At autopsy, both a major tumor mass with
      extensive involvement, located in the surgical margin, and a small mass located
      in S7 were discovered. Microscopically, the major tumor was diagnosed as
      adenosquamous carcinoma and the small one in S7 as hepatocellular carcinoma. To
      our knowledge, this is the first case of a double cancer consisting of
      adenosquamous and hepatocellular carcinomas of the liver. The pathological
      findings support the hypothesis that this tumor developed as a squamous
      transformation of adenocarcinoma.

PMID- 11844071
TI  - Primary low-grade MALT lymphoma of the gallbladder.
AB  - We report a case of primary low-grade B-cell lymphoma of the mucosa-associated
      lymphoid tissue (low-grade MALT lymphoma) in the gallbladder. A 58-year-old woman
      suspected of gallbladder carcinoma underwent laparoscopic cholecystectomy.
      Microscopic examination of the gallbladder demonstrated lymphoid cell
      infiltration forming lymphoid follicles with hyperplastic secondary follicles.
      The surrounding monocytoid B cells and centrocyte-like cells selectively
      infiltrated the crypt epithelium forming lympho-epithelial lesions. Plasma cells
      were also noted beneath the mucosal epithelium. Bile culture revealed the Gram
      negative bacilli Enterococcus faecalis and Morganella morganii. Immunoglobulin
      heavy chain gene rearrangement was confirmed using polymerase chain reaction
      (PCR) and oligoclonal lymphoid proliferations was detected. Because autoimmune
      diseases, or chronic inflammatory disorders, seem to correlate with the
      occurrence of MALT lymphoma, Gram-negative bacterial infection could also be
      considered as a prodrome of MALT lymphoma of the gallbladder.

PMID- 11844072
TI  - Cutaneous bronchogenic cyst of the abdominal wall.
AB  - We report a case of the unusual location of a cutaneous bronchogenic cyst on the
      abdominal wall. The patient was a 9-month-old boy who had presented with a 1.5 cm
      sized polypoid mass, present since birth. Pathological examination of the excised
      mass revealed multiple small cystic structures surrounded by the fibroadipose
      tissue. The lining epithelium consisted of either pseudostratified ciliated
      columnar epithelium with goblet cells or a single layer of ciliated or non
      ciliated cuboidal to columnar cells. The cystic walls contained a well-developed
      smooth muscle bundle, mucous glands and hyaline cartilage plate. This lesion was
      adherent to the peritoneum, but there was no direct communication with the
      abdominal cavity. Cutaneous bronchogenic cyst located in the abdominal wall has
      not been described in the English literature. The present case suggests a
      possible origin from a downward migration, from the sequestered bud of a
      tracheobronchial tree primordium along the midline of the body surface, during
      embryonic development.

PMID- 11844103
TI  - A complex and mobile structure forms a distinct subregion within the continuous
      vacuolar membrane in young cotyledons of Arabidopsis.
AB  - The plant vacuole is a multifunctional organelle which is essential for growth
      and development. To visualize the dynamics of plant vacuolar membranes, gamma-TIP
      (tonoplast intrinsic protein) was fused to GFP and expressed in Arabidopsis
      thaliana. The marker molecule was targeted to the vacuolar membranes in most
      tissues, as expected. In rapidly expanding cells, some additional spherical
      structures were often observed within the lumen of vacuoles, which emitted strong
      fluorescence. To confirm their normal presence, we examined wild-type Arabidopsis
      cotyledons by transmission electron microscopy. The metal-contact rapid-freezing
      method revealed that the vacuolar lumen of epidermal cells contained many
      cytoplasmic projections, which often formed spherical structures (1-3 microm
      diameter) consisting of double membranes. Thus we concluded that these structures
      are authentic and named them 'bulbs'. Three-dimensional reconstruction from
      serial electron microscopic images demonstrates that bulbs are very intricately
      folded, but are continuous with the limiting vacuolar membrane. The fluorescence
      intensity of bulbs is about threefold higher than that of vacuolar membrane. GFP
      AtRab75c, another marker of the vacuole, did not give fluorescent signals of
      bulbs in transgenic plants, but the existence of bulbs was still confirmed by
      electron microscopy. These results suggest that bulbs define a subregion in the
      continuous vacuolar membrane, where some proteins are concentrated and others
      segregated.

PMID- 11844104
TI  - H2O2 plays different roles in determining penetration failure in three diverse
      plant-fungal interactions.
AB  - Fungal plant pathogens that attempt to penetrate and feed on living cells
      frequently trigger a localized plant defence response that results in fungal
      penetration failure. In the current study we demonstrate that breakdown products
      of the cell wall released by the localized application of hemicellulase elicit
      localized responses including, sequentially, extracellular H2O2 generation;
      accumulation of phenolic compounds; and cross-linking of proteins in the cell
      wall. In a detailed time-course study of three plant-fungus interactions that
      result in a high frequency of penetration failure, only one plant-fungus
      combination displayed a similar profile of responses to that induced by localized
      cell-wall degradation. The additional generation of extracellular O2- in one
      interaction, and the absence of phenolic compounds in the cell wall in another,
      demonstrate that plant responses to the penetration process may be influenced by
      activities of the penetrating fungus. Significantly, H2O2 generation was the only
      response detected in all three plant-fungal combinations at the correct time and
      place to account for penetration failure, and in all three combinations the
      enzymatic removal of H2O2 resulted in increased penetration success.
      Pharmacological studies suggest that in two of the three interactions, H2O2
      generation required cytoskeletal involvement but was independent of transcription
      or translation, although inhibition of the latter processes increased fungal
      penetration. In at least one of these two interactions, the data suggest that
      H2O2 generation and new gene expression act within the same penetration
      inhibiting pathway, possibly through the involvement of phenolic materials.
      However, enzymatic removal of H2O2 from the third interaction almost completely
      eliminated penetration failure, while interference with cytoplasmic processes had
      no effect, suggesting that H2O2 generation in this system did not require
      protoplast involvement and, alone, was necessary and sufficient to account for
      fungal penetration failure.

PMID- 11844105
TI  - Evidence of mitochondrial involvement in the transduction of signals required for
      the induction of genes associated with pathogen attack and senescence.
AB  - Using the mRNA differential display technique, seven cDNAs have been isolated
      that are rapidly induced when cultured tobacco (Nicotiana tabacum) cells are
      treated with the mitochondrial electron transport inhibitor antimycin A (AA).
      Interestingly, six of the cDNAs show distinct similarity to genes known to be
      induced by processes that involve programmed cell death (PCD), such as senescence
      and pathogen attack. All of the cDNAs as well as Aox1, a gene encoding the
      alternative oxidase, were found to also be strongly induced by H2O2 and salicylic
      acid (SA). AA, H2O2 and SA treatment of tobacco cells caused a rapid rise in
      intracellular ROS accumulation that, when prevented by antioxidant treatment,
      resulted in inhibition of gene induction. Besides AA, both H2O2 and SA were found
      to disrupt normal mitochondrial function resulting in decreased rates of electron
      transport and a lowering of cellular ATP levels. Furthermore, the pre-treatment
      of tobacco cells with bongkrekic acid, a known inhibitor of the mitochondrial
      permeability transition pore in animal cells, was found to completely block gene
      induction when AA, H2O2 or SA were subsequently added. These findings suggest
      that the mitochondrion may serve an important role in conveying intracellular
      stress signals to the nucleus, leading to alterations in gene expression.

PMID- 11844106
TI  - Small changes in the activity of chloroplastic NADP(+)-dependent ferredoxin
      oxidoreductase lead to impaired plant growth and restrict photosynthetic activity
      of transgenic tobacco plants.
AB  - A ferredoxin-NADP+ oxidoreductase (FNR) cDNA from tobacco (Nicotiana tabacum cv.
      Samsun) was cloned and sequenced. Comparison of the deduced amino acid sequence
      revealed high identity to FNR proteins from Capsicum annuum, Pisum sativum,
      Spinacia oleracea and Vicia faba. Transgenic tobacco plants were generated that
      constitutively express the FNR cDNA in reverse orientation between the CaMV 35S
      promoter and the polyadenylation signal of the octopine synthase gene. Plants
      expressing the FNR antisense gene showed lower levels of FNR mRNA and protein
      accumulation, which was paralleled by a decrease in FNR activity. As a
      consequence, NADPH levels declined whereas NADP+ levels increased, leading to an
      unaltered NADP(H) pool. Growth rates, chlorophyll content and net CO2 uptake
      rates at high and low irradiances were strongly reduced in FNR antisense tobacco
      plants. These changes were accompanied by an over-reduced state of P700 as
      estimated by absorption changes at 820 nm. FNR control coefficients determined
      for the photosynthetic rate at saturating (C(R) = 0.94) and limiting (C(R) =
      0.70) light conditions revealed a prominent role of this reductase in the
      regulation of photosynthesis.

PMID- 11844107
TI  - The oat mitochondrial permeability transition and its implication in victorin
      binding and induced cell death.
AB  - The mitochondrion has emerged as a key regulator of apoptosis, a form of animal
      programmed cell death (PCD). The mitochondrial permeability transition (MPT),
      facilitated by a pore-mediated, rapid permeability increase in the inner
      membrane, has been implicated as an early and critical step of apoptosis.
      Victorin, the host-selective toxin produced by Cochliobolus victoriae, the causal
      agent of victoria blight of oats, has been demonstrated to bind to the
      mitochondrial P-protein and also induces a form of PCD. Previous results suggest
      that a MPT may facilitate victorin's access to the mitochondrial matrix and
      binding to the P-protein: (i) victorin-induced cell death displays features
      similar to apoptosis; (ii) in vivo, victorin binds to the mitochondrial P-protein
      only in toxin-sensitive genotypes whereas victorin binds equally well to P
      protein isolated from toxin-sensitive and insensitive oats; (iii) isolated,
      untreated mitochondria are impermeable to victorin. The data implicate an in vivo
      change in mitochondrial permeability in response to victorin. This study focused
      on whether oat mitochondria can undergo a MPT. Isolated oat mitochondria
      demonstrated high-amplitude swelling when treated with spermine or Ca2+ in the
      presence of the Ca2+-ionophore A23187, and when treated with mastoparan, an
      inducer of the MPT in rat liver mitochondria. In all cases, swelling demonstrated
      size exclusion in the range 0.9-1.7 kDa, similar to that found in animal
      mitochondria. Further, MPT-inducing conditions permitted victorin access to the
      mitochondrial matrix and binding to the P-protein. In vivo, victorin treatment
      induced the collapse of mitochondrial transmembrane potential within 2 h,
      indicating a MPT. Also, the victorin-induced collapse of membrane potential was
      clearly distinct from that induced by uncoupling respiration, as the latter event
      prevented the victorin-induced PCD response and binding to P-protein. These
      results demonstrate that a MPT can occur in oat mitochondria in vitro, and are
      consistent with the hypothesis that an MPT, which allows victorin access to the
      mitochondrial matrix and binding to the P-protein, occurs in vivo during victorin
      induced PCD.

PMID- 11844108
TI  - 5S rRNA genes expression is not inhibited by DNA methylation in Arabidopsis.
AB  - Methylation has often been correlated with transcriptional inhibition of genes
      transcribed by polymerase II, but its role on polymerase III genes is less well
      understood. Using the genomic sequencing technique, we have analysed the
      methylation pattern of the different 5S-rDNA arrays of the Arabidopsis genome.
      Every cytosine position within the 5S sequence is highly methylated whatever the
      context - CpG, CpNpG or non-symmetrical. The methylation pattern of both
      transcribed and non-transcribed 5S units is similar, with no preferential
      methylated or unmethylated site. These results, taken together with 5-azacytidine
      treatments and in vitro transcription experiments using methylated 5S templates,
      demonstrate that 5S rRNA gene transcription is not inhibited by methylation. Non
      transcribed 5S arrays are more subject to transition mutations resulting from
      deamination of 5-methylcytosines, leading to CpG depletions and an increasing A +
      T content. As there were no detectable differences in methylation, this implies
      more efficient repair and/or selection pressure in transcribed 5S-blocks.

PMID- 11844109
TI  - Shoot-derived auxin is essential for early lateral root emergence in Arabidopsis
      seedlings.
AB  - Lateral root formation is profoundly affected by auxins. Here we present data
      which indicate that light influences the formation of indole-3-acetic acid (IAA)
      in germinating Arabidopsis seedlings. IAA transported from the developing leaves
      to the root system is detectable as a short-lived pulse in the roots and is
      required for the emergence of the lateral root primordia (LRP) during early
      seedling development. LRP emergence is inhibited by the removal of apical tissues
      prior to detection of the IAA pulse in the root, but this treatment has minimal
      effects on LRP initiation. Our results identify the first developing true leaves
      as the most likely source for the IAA required for the first emergence of the
      LRP, as removal of cotyledons has only a minor effect on LRP emergence in
      contrast to removal of the leaves. A basipetal IAA concentration gradient with
      high levels of IAA in the root tip appears to control LRP initiation, in contrast
      to their emergence. A significant increase in the ability of the root system to
      synthesize IAA is observed 10 days after germination, and this in turn is
      reflected in the reduced dependence of the lateral root emergence on aerial
      tissue-derived auxin at this stage. We propose a model for lateral root formation
      during early seedling development that can be divided into two phases: (i) an LRP
      initiation phase dependent on a root tip-localized IAA source, and (ii) an LRP
      emergence phase dependent on leaf-derived IAA up to 10 days after germination.

PMID- 11844110
TI  - Involvement of extracellular calcium influx in the self-incompatibility response
      of Papaver rhoeas.
AB  - We have previously demonstrated that increases in cytosolic free Ca2+ are
      triggered by the self-incompatibility (SI) response in incompatible Papaver
      rhoeas (the field poppy) pollen. However, one key question that has not been
      answered is whether extracellular Ca2+ may be involved. To address this question,
      we have used an ion-selective vibrating probe to measure changes in extracellular
      Ca2+ fluxes around poppy pollen tubes. Our data reveal several findings. First,
      we confirm that there is an oscillating Ca2+ influx directed at the apex of the
      pollen tube; we also provide evidence that Ca2+ influx also occurs at the shanks
      of pollen tubes. Second, upon challenge with self-incompatibility (S) proteins,
      there is a stimulation of Ca2+ influx along the shank of incompatible pollen
      tubes, approximately 50 microm behind the pollen tube tip. This demonstration of
      SI-induced Ca2+ influx suggests a role for influx of extracellular Ca2+ in the SI
      response.

PMID- 11844112
TI  - Entopically additive expression of GLABRA2 alters the frequency and spacing of
      trichome initiation.
AB  - GLABRA2 (GL2)/ATHB-10 encodes a homeodomain protein that belongs to the
      homeodomain-leucine zipper family. Mutant studies have revealed that this gene is
      involved in trichome, root-hair and seed-coat development. We used reverse
      genetics to investigate the role of GL2 in trichome development. A transgene
      consisting of a GL2-coding fragment preceded by the cauliflower mosaic virus 35S
      promoter (35S::GL2) did not complement defects in the gl2-1 mutant. In the wild
      type genetic background, 35S::GL2 caused gl2-mutant-like and scarcely viable
      phenotypes, suggesting that ectopic overexpression of GL2 interrupts endogenous
      GL2 function in trichome development and is toxic to plants. On the other hand,
      another GL2 transgene containing the GL2 promoter (pGL2::GL2) complemented the
      gl2-1 mutation. Entopically additive expression of GL2 by introduction of
      pGL2::GL2 in the wild-type genetic background noticably increased the number of
      trichomes and induced production of adjacent trichomes. Consistent with this
      result, gl2-1/+ heterozygous leaves, whose GL2 expression was expected to
      decrease, had fewer trichomes than +/+ leaves. These results indicate that GL2
      quantitatively regulates the frequency of trichome initiation and is involved in
      determining trichome spacing.

PMID- 11844111
TI  - Arabidopsis glt1-T mutant defines a role for NADH-GOGAT in the non
      photorespiratory ammonium assimilatory pathway.
AB  - The physiological role of the NADH-dependent glutamine-2-oxoglutarate
      aminotransferase (NADH-GOGAT) enzyme was addressed in Arabidopsis using gene
      expression analysis and by the characterization of a knock-out T-DNA insertion
      mutant (glt1-T) in the single NADH-GOGAT GLT1 gene. The NADH-GOGAT GLT1 mRNA is
      expressed at higher levels in roots than in leaves. This expression pattern
      contrasts with GLU1, the major gene encoding Fd-GOGAT, which is most highly
      expressed in leaves and is involved in photorespiration. These distinct organ
      specific expression patterns suggested a non-redundant physiological role for the
      NADH-GOGAT and Fd-GOGAT gene products. To test the in vivo function of NADH
      GOGAT, we conducted molecular and physiological analysis of the glt1-T mutant,
      which is null for NADH-GOGAT, as judged by mRNA level and enzyme activity.
      Metabolic analysis showed that the glt1-T mutant has a specific defect in growth
      and glutamate biosynthesis when photorespiration was repressed by 1% CO2. Under
      these conditions, the glt1-T mutant displayed a 20% decrease in growth and a
      dramatic 70% reduction in glutamate levels. Herein, we discuss the significance
      of NADH-GOGAT in non-photorespiratory ammonium assimilation and in glutamate
      synthesis required for plant development.

PMID- 11844113
TI  - High free-methionine and decreased lignin content result from a mutation in the
      Arabidopsis S-adenosyl-L-methionine synthetase 3 gene.
AB  - As an approach to understand the regulation of methionine (Met) metabolism,
      Arabidopsis Met over-accumulating mutants were isolated based on their resistance
      to selection by ethionine. One mutant, mto3, accumulated remarkably high levels
      of free Met - more than 200-fold that observed for wild type - yet showed little
      or no difference in the concentrations of other protein amino-acids, such as
      aspartate, threonine and lysine. Mutant plants did not show any visible growth
      differences compared with wild type, except a slight delay in germination.
      Genetic analysis indicated that the mto3 phenotype was caused by a single,
      recessive mutation. Positional cloning of this gene revealed that it was a novel
      S-adenosylmethionine synthetase, SAMS3. A point mutation resulting in a single
      amino-acid change in the ATP binding domain of SAMS3 was determined to be
      responsible for the mto3 phenotype. SAMS3 gene expression and total SAMS protein
      were not changed in mto3; however, both total SAMS activity and S
      adenosylmethionine (SAM) concentration were decreased in mto3 compared with wild
      type. Lignin, a major metabolic sink for SAM, was decreased by 22% in mto3
      compared with wild type, presumably due to the reduced supply of SAM. These
      results suggest that SAMS3 has a different function(s) in one carbon metabolism
      relative to the other members of the SAMS gene family.

PMID- 11844116
TI  - Infection of replication-deficient adenoviral vector enhances interleukin-8
      production in small airway epithelial cells more than in large airway epithelial
      cells.
AB  - OBJECTIVE: In clinical trials or experiments of gene therapy, airway
      administration of an adenoviral-based vector (E1A-deleted) elicits a dose
      dependent inflammatory response with limitation in the duration of transgene
      expression. The purpose of this study was to evaluate the possibility that the
      adenoviral-based vector directly enhances IL-8 production independent of
      adenoviral E1A in normal human airway epithelial cells and to examine the
      different responses between primary human bronchial epithelial cells (HBE) and
      primary human small airway epithelial cells (HSAE) in production of IL-8
      following exposure to an adenovirus vector. METHODOLOGY: Interleukin (IL)-8
      levels were evaluated in the culture medium from HBE and HSAE treated with
      increasing doses of E1A-deleted adenoviral vector contained the Escherichia coli
      LacZ reporter gene (AdCMVLacZ). To clarify the mechanism of enhancing IL-8
      production in airway epithelial cells by infection with adenovirus vector,
      alphavbeta5 agonistic antibody as an analogue of adenoviral capsid and adenoviral
      capsid vector denatured by exposure to ultraviolet (UV) light were used in the
      present study. RESULTS: Inoculation of HBE with AdCMVLacZ at a multiplicity of
      infection (MOI) of between 1 and 200 resulted in a dose-dependent expression of
      LacZ, and maximal expression was observed at a MOI of 100. In contrast,
      inoculation of HSAE with AdCMVLacZ resulted in maximum expression of LacZ at a
      MOI of 10. Interleukin-8 levels in culture media from the same experiments
      revealed significantly greater production of IL-8 in HSAE inoculated with
      AdCMVLacZ at a MOI of 50, compared to HBE under the same conditions. The capsid
      denatured adenoviral vector did not enhance IL-8 production, and alphavbeta5
      agonistic antibody induced IL-8 enhancement. CONCLUSION: These results suggest
      that the adenoviral vector directly induces the expression of airway epithelial
      inflammatory cytokines in the pathogenesis of inflammation and that small airway
      cells have a greater affinity for adenovirus than other airway epithelial cells.

PMID- 11844117
TI  - Comparing transforming growth factor beta-2 and fibronectin as pleurodesing
      agents.
AB  - BACKGROUND: We have recently demonstrated that transforming growth factor beta-2
      (TGF-beta2) can produce effective pleurodesis. Whether this effect can be
      reproduced by the use of its downstream proteins is not known. This study
      compared the effectiveness of TGF-beta2 and fibronectin in inducing pleurodesis
      in rabbits. METHODOLOGY: New Zealand white rabbits (1.5-2.0 kg) were given 1.7
      microg of TGF-beta2 (n=5) or 2.0 mg of cellular fibronectin (n=4) intrapleurally
      via a chest tube. The induced pleural fluid was collected and analyzed. The
      rabbits were sacrificed after 14 days. The pleurodesis was graded macroscopically
      from 1 (none) to 8 (symphysis > 50%). RESULTS: All rabbits in the TGF-beta2 group
      developed effective pleurodesis while none in the fibronectin group had scores >
      2 (pleurodesis scores 7.0 +/- 0.6 vs 1.3 +/- 0.3, P < 0.001). Rabbits that
      received TGF-beta2 produced large amounts of pleural fluid initially (< 4 days).
      Microscopically, the pleura of rabbits in the TGF-beta2 group showed prominent
      spindle cell proliferation and collagen deposition, but no significant
      inflammation or mesothelial proliferation. Pleural tissues of rabbits in the
      fibronectin group had occasional thin collagen deposits only. The intrapleural
      administration of 2.0 mg of fibronectin, a downstream product of TGF-beta, did
      not induce effective pleurodesis, as did the intrapleural administration of TGF
      beta2. CONCLUSIONS: The present study suggests that the mechanism by which TGF
      beta2 induces pleurodesis is not predominantly dependent on the production of
      fibronectin.

PMID- 11844114
TI  - Runaway cell death, but not basal disease resistance, in lsd1 is SA- and
      NIM1/NPR1-dependent.
AB  - LSD1 was defined as a negative regulator of plant cell death and basal disease
      resistance based on its null mutant phenotypes. We addressed the relationship
      between lsd1-mediated runaway cell death and signaling components required for
      systemic acquired resistance (SAR), namely salicylic acid (SA) accumulation and
      NIM1/NPR1. We present two important findings. First, SA accumulation and
      NIM1/NPR1 are required for lsd1-mediated runaway cell death following pathogen
      infection or application of chemicals that mimic SA action. This implies that
      lsd1-dependent cell death occurs 'downstream' of the accumulation of SA. As SA
      application triggers runaway cell death in lsd1 but not wild-type plants, we
      infer that LSD1 negatively regulates an SA-dependent signal leading to cell
      death. Thus SA is both a trigger and a required mediator of lsd1 runaway cell
      death. Second, neither SA accumulation nor NIM1/NPR1 function is required for the
      basal resistance operating in lsd1. Therefore LSD1 negatively regulates a basal
      defense pathway that can act upstream or independently of both NIM1/NPR1 function
      and SA accumulation following avirulent or virulent pathogen challenge. Our data,
      together with results from other studies, point to the existence of an SA
      dependent 'signal potentiation loop' controlling HR. Continued escalation of
      signaling in the absence of LSD1 leads to runaway cell death. We propose that
      LSD1 is a key negative regulator of this signal potentiation.

PMID- 11844118
TI  - Using baseline respiratory function data to optimize cycle exercise test
      duration.
AB  - BACKGROUND: It is often difficult to select an appropriate workload increment for
      progressive cycle exercise tests in order to achieve optimal test duration (8-12
      min). We hypothesize that baseline respiratory function can be systematically
      used to select appropriate workload increment to optimize test duration in
      patients referred to the clinical laboratory. METHODOLOGY: One hundred and eighty
      consecutive exercise tests (with increments of 15 W/min) were retrospectively
      assessed. Using regression analysis, an equation was generated that predicts the
      work rate increment that would provide exercise duration of 8-12 min. The
      validity of this equation was tested prospectively in 231 consecutive tests
      performed with the calculated workload increment rounded to the nearest 5 watts
      (W). RESULTS: The best regression equation was: workload increment (W/min)=1.94 x
      FEV1 (L) + 0.63 x TLCO (mmol/min per kPa) - 0.07 x age + 1.94 x gender (male=1,
      female=0) + 4.12 (r=0.85, P < 0.0001). Using this equation allowed selection of
      the most appropriate workload increment in 79% of tests and reduced the number of
      tests of non-optimal duration from 72% (for a fixed increment of 15 W/min) to
      38%. CONCLUSIONS: Utilization of this regression equation allows standardization
      in the selection of workload increment, and reduces the number of cycle exercise
      tests of inadequate duration.

PMID- 11844119
TI  - Characteristics of patients with lung cancer under the age of 45 years: a case
      control study.
AB  - OBJECTIVE: The aim of this study was to define the clinical and pathological
      features associated with lung cancer diagnosed in persons under the age of 45
      compared with lung cancer in an older population of greater than 45 years.
      METHODOLOGY: A case control study was undertaken. Cases were defined as patients
      diagnosed with lung cancer under the age of 45 years. Controls were lung cancer
      patients over 45 years matched only for the date of diagnosis. Up to four
      controls were selected for each case. A retrospective review was undertaken of
      the records of a single tertiary respiratory institution which served a
      population of 1.2 million. RESULTS: Forty-eight cases of lung cancer (< 45 years
      of age) were identified and were compared to 123 matched controls with lung
      cancer (> 45 years of age). Of the cases 67% were female compared with 32% female
      cases in the control group (P < 0.01). The rate of adenocarcinoma was
      significantly higher among cases (48% vs 27%, P=0.001), while squamous cell
      carcinoma was more common in the controls (35% vs 17% P =0.001). Smoking was
      common in both groups although less so among cases (79% vs 95%, P=0.001)). There
      was no difference in survival rates between the cases (11 months) compared with
      controls (8 months) (P=0.1). CONCLUSIONS: Young lung cancer patients were
      predominantly female and adenocarcinoma accounted for a disproportionate number
      of the histological types. Cigarette smoking appears to be the main aetiological
      agent but as 21% of the patients under 45 years were non-smokers, other factors
      (genetic/hormonal) may also contribute. This study has not demonstrated a worse
      outcome in younger patients.

PMID- 11844120
TI  - A randomized trial of peak-flow and symptom-based action plans in adults with
      moderate-to-severe asthma.
AB  - OBJECTIVE: Peak flow meters (PFM) continue to be recommended as an important part
      of asthma self-management plans. It remains unclear if there is an advantage in
      using PFM in people with moderate-to severe asthma who are not poor perceivers of
      bronchoconstriction. METHODOLOGY: Prospective, randomized controlled trial of 134
      adults with moderate-to-severe asthma who did not have evidence of poor
      perception of bronchoconstriction on histamine challenge testing, who were
      recruited from inpatients and outpatients of a university teaching hospital.
      Comparison was made over 12 months of the effectiveness of written action plans
      using either peak flow monitoring or symptoms to guide management. Subjects were
      contacted at monthly intervals by telephone for reinforcement and evaluation of
      use of the action plans, and to provide ongoing education. Spirometry and PD20
      histamine were measured at 3-monthly intervals. Measures of health care
      utilization and morbidity (asthma exacerbations; hospitalizations; emergency
      department (ED) visits; days absent from work or school due to asthma; medication
      use and a self-rating of asthma severity) were made monthly. A psychosocial
      questionnaire (attitudes and beliefs, state-trait anxiety, denial) was given at
      entry and at 12-months or at withdrawal from the study. RESULTS: There were
      significant improvements for both groups for hospitalizations, ED visits, days
      off from school or work, and PD20 histamine, but no between-group differences.
      Appropriate use of action plans was 85% in the symptoms group and 86% in the PFM
      group. For all subjects, those who subsequently had an ED visit had significantly
      higher levels of denial (P=0.04) and lower scores for self-confidence (P=0.04),
      compared to those who did not have an ED visit. CONCLUSIONS: Use of written
      action plans, combined with regular contact to reinforce self-management,
      improved airway reactivity and reduced health care utilization. However, use of
      PFM was not superior to symptom-based plans.

PMID- 11844121
TI  - Can serial qualitative polymerase chain reaction monitoring predict outcome of
      pulmonary tuberculosis treatment?
AB  - BACKGROUND: The aim of this study was to assess the use of qualitative one-tube
      nested polymerase chain reaction (PCR) for monitoring the treatment response in
      smear-positive pulmonary tuberculosis, and the factors determining the negative
      conversion of sputum smear, culture, and PCR during treatment. METHODOLOGY: A
      total of 53 patients receiving a standard short course of chemotherapy with 24
      months follow-up period after treatment cessation were included in the study.
      Sputum specimens were collected serially for smear, culture, and PCR until the
      treatment was complete. RESULTS: The conversion rate for sputum culture, smear,
      and PCR at 8 weeks after treatment were 84.9, 58.5, and 47.1%, and at 16 weeks of
      treatment were 100, 88.7, and 79.2%, respectively. At the end of the treatment
      period, there were four PCR persisters, one of whom had disease relapse. Only
      cavitary disease had an influence over the negative conversion of the smear and
      PCR at 8 weeks (RR 3.5, 95% CI 1.04-11.95, P=0.04 for smear; RR 5.06, 95% CI
      1.196-21.42, P=0.03 for PCR). CONCLUSION: Qualitative PCR was not useful for
      monitoring therapy in smear-positive pulmonary tuberculosis. Mycobacterium DNA
      was cleared slowly in cavitary disease. The PCR may be performed at the time of
      treatment cessation to identify those with potential for disease relapse.

PMID- 11844122
TI  - Clinical significance of potential pathogenic microorganisms of sputum in
      patients with pulmonary tuberculosis.
AB  - BACKGROUND: Bacterial culture of sputum is frequently positive in patients with
      pulmonary tuberculosis (TB). However, it remains to be clarified whether
      detection of potential pathogenic microorganisms (PPM) in sputum represents
      bacterial infection or only colonization of the respiratory tract. In the present
      study, we investigated the clinical significance of PPM in patients with
      pulmonary TB. METHODOLOGY: Sputum culture for PPM was studied in 174 pulmonary TB
      patients (117 males and 57 females, mean age of 71 years) on the day of
      admission. Ninety-seven patients (63 males and 34 females, mean age of 67.1
      years) also underwent transtracheal aspirates (TTA). Quantitative culture of
      sputum and TTA was performed to distinguish infection from colonization. The
      results were evaluated as follows: more than 106 or 105 c.f.u./mL indicated
      infection in the case of sputum or TTA samples, respectively. We also compared
      various clinical parameters between patients with PPM and patients with non
      potential pathogenic microorganisms (non-PPM). RESULTS: Potential pathogenic
      microorganisms were positive in 44% and 24% of sputum and TTA specimens,
      respectively. However, quantitative culture for PPM showed positive findings in
      only 11% and 3% of sputum and TTA specimens, respectively. A comparative study of
      the clinical features revealed that PPM patients had a lower bodyweight and lower
      serum albumin levels than non-PPM patients. A fatal outcome was also more common
      in PPM patients than in non-PPM patients. Logistic regression analysis further
      confirmed that PPM clearly contributed to a fatal outcome in addition to the
      previously established parameters including age, performance status, haemoglobin,
      albumin and radiographic disease extent. CONCLUSION: Although sputum PPM
      represent only colonization of the upper respiratory tract in TB patients, they
      are associated with a poor prognosis.

PMID- 11844123
TI  - Progressive rise of Mycobacterium tuberculosis resistance to rifampicin and
      streptomycin in Riyadh, Saudi Arabia.
AB  - OBJECTIVE: The aim of this study was to investigate, for the first time, the
      factors associated with resistance to antituberculous drugs in Saudi Arabia, and
      to follow the long-term trends in drug resistance. METHODOLOGY: A retrospective
      study of patients with positive Mycobacterium tuberculosis recorded at the Riyadh
      Tuberculosis Center in 1990 was undertaken. The resistance figures from the same
      centre for the period July 1996 to June 1997 were reviewed for comparison.
      RESULTS: Resistance was significantly higher in those previously treated (71%)
      than in those who denied previous treatment (34%). There was a trend towards
      association of resistance with cavitatory, multilobar, and acid fast bacilli
      positive cases. Nationality (Saudis, Yemenis, others) had no significant effect
      on resistance. The Riyadh Region now has the same high prevalence of rifampicin
      resistance as previously reported in the Western Region of the Kingdom. The
      figures on resistance for the years 1986-88, 1990, and 1996-97 were: isoniazid
      19.5/13.8/11.1%, rifampicin 10/20.7/24.6%, streptomycin 5/22/27.4%, ethambutol
      3.7/3.9/1.8%, respectively. The reduction in isoniazid and ethambutol resistance
      coincided with a rise in resistance to rifampicin and streptomycin. We speculate
      that this resulted from the fact that isoniazid and ethambutol are restricted
      only to the treatment of tuberculosis and cannot, by law, be dispensed by general
      practitioners or private pharmacies. Rifampicin and streptomycin, however, are
      widely used for brucellosis; an endemic disease in Saudi Arabia where up to 12
      weeks of rifampicin therapy is recommended. CONCLUSIONS: There has been a
      significant increase in rifampicin and streptomycin resistance in Saudi Arabia
      over the last 10 years. Possible causes include poor compliance and wide use of
      these two drugs for non-tuberculosis conditions. These findings could jeopardize
      the benefits of the directly observed therapy short course policy which is being
      implemented in Saudi Arabia. Consideration should be given to prohibiting the
      routine use of rifampicin for the treatment of brucellosis.

PMID- 11844124
TI  - Prognostic factors in severe community-acquired pneumonia in patients without co
      morbid illness.
AB  - OBJECTIVES: We wished to determine the prognostic factors and the impact of
      initial empirical antibiotic therapy on the outcome of severe community-acquired
      pneumonia in patients without underlying co-morbid illness. METHODOLOGY: This is
      a retrospective record review of consecutive patients with severe community
      acquired pneumonia who were divided into those with and without underlying co
      morbid illness. RESULTS: There were 182 patients including 112 primary (no co
      morbid illness) and 70 secondary (underlying co-morbid illness) pneumonias. The
      overall mortality was 41.8% and there were no differences in APACHE II score or
      mortality when comparing cases with primary (37.5%) and secondary infections
      (48.6%). The mortality was significantly higher in patients with negative
      microbiology. Univariate analysis identified a number of parameters and various
      antibiotic regimens, which appeared to be associated with a significantly poorer
      outcome. On multivariate analysis multilobar pulmonary consolidation, need for
      mechanical ventilation, inotropes and dialysis were documented to be independent
      predictors of mortality. Only in their absence could different antibiotic
      regimens be shown to have an apparent impact on outcome and further analysis
      suggested that the reason for these differences related predominantly to
      differences in the severity of the infection. CONCLUSIONS: Markers of disease
      severity appear to be the most important predictors of outcome in patients with
      severe community-acquired pneumonia.

PMID- 11844125
TI  - Longitudinal follow-up study of 11 patients with pulmonary
      lymphangioleiomyomatosis: diverse clinical courses of LAM allow some patients to
      be treated without anti-hormone therapy.
AB  - OBJECTIVE: The purpose of this study is to clarify the existing issues on the
      clinical diversity, natural history, and mode of disease progression of pulmonary
      lymphangioleiomyomatosis (LAM). METHODOLOGY: Eleven patients with LAM were
      reviewed retrospectively with special reference to serial changes in pulmonary
      function and radiological findings during the course of their disease, treatment,
      and outcome. All patients were female with a mean age of 33.8 years at
      presentation and the observation period ranged from 2.1 to 20.8 years (mean 7.4
      years). RESULTS: Four of six patients, treated with anti-hormone therapy,
      presented with exertional dyspnoea, marked airflow limitation (forced expiratory
      volume in 1 s/forced vital capacity, 23-38%), and severely impaired diffusing
      capacity (%DLCO, 21.4-36% of the predicted). The remaining two patients showed
      only a decreased diffusing capacity (70.6% and 59.4% of the predicted) which
      rapidly deteriorated with subsequent development of airflow limitation. Repeated
      chest computed tomographic (CT) examinations revealed increasing numbers of cysts
      with simultaneous loss of normal lung parenchyma in these two patients. In
      contrast, the five patients who received no anti-hormone therapy had no
      respiratory symptoms aside from pneumothorax at onset. Remarkable differences
      were noted, with pulmonary function being well maintained and slow progression of
      cystic changes on CT being observed in the latter group. CONCLUSIONS: Diverse
      clinical courses observed in patients with pulmonary LAM can be well delineated
      and assessed by periodic examinations including pulmonary function tests and
      chest CT imaging. Anti-hormone therapy is not always necessary for a certain
      group of LAM patients and they appear to have a stable course and favourable
      outcomes without anti-hormone treatment.

PMID- 11844126
TI  - Is it possible to detect ulcerative colitis-related respiratory syndrome early?
AB  - OBJECTIVE: Obstructive airway disease, bronchiectasis, non-specific parenchymal
      infiltration and bronchiolitis obliterans organizing pneumonia are seen
      occasionally in patients with inflammatory bowel disease. In the present study,
      we evaluated ulcerative colitis (UC) patients for latent pulmonary involvement.
      METHODS: Fifteen patients (nine females, six males, mean age 44 years) were
      admitted into the study. All patients were free of respiratory symptoms.
      Ulcerative colitis was active in nine patients and all patients were using anti
      inflammatory treatment. Pulmonary function tests (PFT), high resolution computed
      tomography of thorax (HRCT) and bronchoscopy with bronchoalveolar lavage (BAL)
      and transbronchial biopsy (TBLB) were carried out in all subjects. RESULTS: Mild
      airways obstruction was found in 1 of 13 patients. High resolution CT was
      abnormal in 4 of 15 patients. Ground glass appearance suggestive of an
      interstitial lung disease was present in three patients. Radiolucency and
      pneumocysts were present in the fourth patient suggesting obstructive small
      airway disease. High resolution CT findings correlated with disease activity (P <
      0.05). Fiberoptic bronchoscopy was performed in 10 patients. A mixed type
      alveolitis was detected in BAL fluid in five patients. In eight patients, TBLB
      showed alveolar septal thickening by connective tissue, lymphocytic accumulation
      in the septal area and minimal septal fibrosis, suggesting subclinical pulmonary
      parenchymal involvement linked to UC. CONCLUSIONS: Our data suggest that latent
      interstitial pulmonary involvement may occur during the course of UC, despite an
      absence of symptoms of lung disease.

PMID- 11844127
TI  - Primary pulmonary botryomycosis: an important differential diagnosis for lung
      cancer.
AB  - This is the sixteenth reported case of pulmonary botryomycosis, an uncommon
      suppurative bacterial infection of the lung. We describe the case of a 69-year
      old man who presented with a chronic cough and intermittent haemoptysis and on
      subsequent chest computed tomographic scan imaging was found to have a right
      lower lobe mass. He underwent a right lower lobectomy for presumed lung cancer.
      Histological analysis however revealed a bacterial aetiology. The past literature
      is reviewed outlining the pathogenesis and difficulties of clinical and
      radiological diagnosis. Primary pulmonary botryomycosis forms an important
      curative differential diagnosis for lung cancer.

PMID- 11844128
TI  - Pulmonary cryptococcosis: a case report and review of the Asian-Pacific
      experience.
AB  - Pulmonary cryptococcosis is a very rare form of pneumonia, which is seldom seen
      among immunocompetent patients. We report the case of a 36-year-old man who
      presented with indolent pneumonia that was subsequently diagnosed to be pulmonary
      cryptococcosis without other systemic involvement. Contrary to formal belief,
      there was evidence of residual lung fibrosis 12 months after initial
      presentation. The features of pulmonary cryptococcosis reported in the Asian
      Pacific region are also reviewed.

PMID- 11844129
TI  - Effect of pulse steroid therapy in a patient with Langerhans' cell histiocytosis.
AB  - Langerhans' cell histiocytosis (LCH) is a condition in which granulomas form in
      various tissues through the accumulation of abnormal histiocytes (Langerhans'
      cells), granulocytes and lymphocytes. An important distinction between LCH and
      primary pulmonary histiocytosis (PPH) is that smoking cessation is known to often
      lead to spontaneous improvement in PPH patients, while this has not been
      demonstrated in patients with multisystem LCH. In this case report, we describe
      the case of a 20-year-old man who presented with cough and palpably enlarged
      lymph nodes in his neck. An inguinal lymph node biopsy led to the diagnosis of
      multisystem LCH in the lungs, the cervical, intra-abdominal, and inguinal lymph
      nodes and the spleen. The patient was a smoker, and had averaged 30 cigarettes
      per day for 7 years. To address the multisystem involvement, intravenous pulse
      steroid therapy was administered (30-40 mg/kg daily) in two 3-day treatment
      periods separated by 3-4 weeks. The patient was also advised to stop smoking, and
      did so. Serial follow-up examinations confirmed an objective improvement with
      complete remission. The patient was still healthy at 18 months post-treatment,
      reflecting a dramatic and positive response to pulse steroid therapy. This
      encouraging result makes this case an important one to highlight.

PMID- 11844132
TI  - Inherited defects of platelet function.
AB  - Inherited platelet defects bleeding syndromes underlie of varying severity. The
      Bernard-Soulier syndrome and Glanzmann thrombasthenia are disorders of membrane
      glycoproteins. In the former, a deficiency of the GPIb-IX-V complex leads to
      defective platelet adhesion, while in thrombasthenia, platelet aggregation does
      not occur in the absence of the integrin alphaIIbbeta3. Defects of primary
      receptors for stimuli are increasingly being described, and include a defect of a
      newly cloned Gi-protein-linked, seven transmembrane domain, ADP receptor. These
      lead to agonist-specific deficiencies in the platelet function response, as do
      abnormalities in the many intracellular signaling pathways of platelets. Defects
      affecting secretion from dense bodies and alpha-granules, of ATP production and
      generation of procoagulant activity, are also encountered. Some disorders are
      exclusive to megakaryocytes and platelets, while in others, such as the Chediak
      Higashi, Hermansky-Pudlak and Wiskott-Aldrich syndromes; the molecular lesion
      extends to other cell types. Disorders affecting platelet morphology, the so
      called "giant platelet" syndromes should also be considered. In familial
      thrombocytopenias, platelets are produced in insufficient quantities to assure
      hemostasis. Platelet disorders are examples of rare diseases; nevertheless they
      have provided essential information in the elucidation of the molecular basis of
      platelet function.

PMID- 11844130
TI  - Allergic bronchopulmonary aspergillosis: a rare cause of pleural effusion.
AB  - Aspergillus fumigatus is one of the most ubiquitous of the airborne saprophytic
      fungi. Allergic bronchopulmonary aspergillosis (ABPA) is a syndrome seen in
      patients with asthma and cystic fibrosis, and is characterized by
      hypersensitivity to chronic colonization of the airways with A. fumigatus. We
      report the case of a patient with ABPA presenting with pleural effusion. A 27
      year-old male was referred with recurrent right pleural effusion. Past medical
      history was remarkable for asthma, allergic sinusitis, and recurrent pleurisy.
      Investigations revealed peripheral eosinophilia with elevated serum
      immunoglobulin E and bilateral pleural effusions with bilateral upper lobe
      proximal bronchiectasis. Precipitating serum antibodies to A. fumigatus were
      positive and the A. fumigatus immediate skin test yielded a positive reaction. A
      diagnosis of ABPA associated with bilateral pleural effusions was made and the
      patient was commenced on prednisolone. At review, the patient's symptoms had
      considerably improved and his pleural effusions had resolved. ABPA may present
      with diverse atypical syndromes, including paratracheal and hilar adenopathy,
      obstructive lung collapse, pneumothorax and bronchopleural fistula, and allergic
      sinusitis. Allergic bronchopulmonary aspergillosis is a rare cause of pleural
      effusion and must be considered in the differential diagnosis of patients
      presenting with a pleural effusion, in particular those with a history of asthma.

PMID- 11844133
TI  - Von Willebrand factor and von Willebrand disease.
AB  - von Willebrand disease (vWD) is caused by quantitative and/or qualitative defects
      of the von Willebrand factor (vWF), a multimeric high molecular weight
      glycoprotein. Typically, it affects the primary hemostatic system, which results
      in a mucocutaneous bleeding tendency simulating a platelet function defect. The
      vWF promotes its function in two ways: (i) by initiating platelet adhesion to the
      injured vessel wall under conditions of high shear forces, and (ii) by its
      carrier function for factor VIII in plasma. Accumulating knowledge of the
      different clinical phenotypes and the pathophysiological basis of the disease
      translated into a classification that differentiated between quantitative and
      qualitative defects by means of quantitative and functional parameters, and by
      analyzing the electrophoretic pattern of vWF multimers. The advent of molecular
      techniques provided the opportunity for conducting genotype-phenotype studies
      which have recently helped, not only to elucidate or confirm important functions
      of vWF and its steps in post-translational processing, but also many disease
      causing defects. Acquired von Willebrand syndrome (avWS) has gained more
      attention during the recent years. An international registry was published and
      recommendation by the Scientific and Standardization Committee of the
      International Society on Thrombosis and Haemostasis in 2000. It concluded that
      avWS, although not a frequent disease, is nevertheless probably underdiagnosed.
      This should be addressed in future prospective studies. The aim of treatment is
      the correction of the impaired hemostatic system of the patient, ideally
      including the defects of both primary and secondary hemostasis. Desmopressin is
      the treatment of choice in about 70% of patients, mostly with type 1, while the
      others merit treatment with concentrates containing vWF.

PMID- 11844134
TI  - Autosomal recessive deficiencies of coagulation factors.
AB  - Deficiencies of coagulation factors that cause a bleeding disorder, other than
      factor VIII and factor IX, are inherited as autosomal recessive traits and are
      generally rare, with prevalence in the general population varying between 1 in
      500 000 and 1 in 2 000 000. In the last few years, the number of patients with
      recessively transmitted coagulation deficiencies has increased in European
      countries with a high rate of immigration of Islamic populations where
      consanguineous marriages are frequent. As a consequence of the relative rarity of
      these deficiencies, the type and severity of bleeding symptoms, the underlying
      molecular defects and the actual management of bleeding episodes are not as well
      established as for hemophilia A and B. This article reviews these disorders, in
      terms of clinical manifestations and characterization of the molecular defects.
      The general principles of management are also discussed.

PMID- 11844135
TI  - Acquired hemophilia.
AB  - Acquired hemophilia is a serious coagulopathy usually affecting the elderly,
      persons with autoimmune disorders and, infrequently, women in the immediate
      postpartum period. It is due to autoantibodies directed against specific domains
      of the factor VIII molecule, leading to inhibition of factor VIII binding to von
      Willebrand factor, to activated factor IX or to negatively charged phospholipids.
      This results in bleeding into the skin, muscles, gastrointestinal and
      genitourinary tracts, and other sites. Mixing patient plasma with normal plasma
      prolongs the activated partial thromboplastin time of the normal plasma and the
      Bethesda assay provides a quantitative estimate of the strength of the inhibitor.
      The selection of therapeutic concentrates for the management of acute bleeding is
      related to the titer of the inhibitor; if less than 5 Bethesda Units, human
      factor VIII may be effective, but higher titer inhibitors usually respond only to
      porcine factor VIII, recombinant factor VIIa or activated prothrombin complex
      concentrates. Corticosteroid treatment leads to disappearance of the autoantibody
      in 50% of patients; cyclophosphamide and cyclosporine are effective in many who
      do not respond to steroids. Occasionally, high dose intravenous immunoglobulin or
      immunosorbent columns transiently decrease inhibitor titers and enable control of
      bleeding. Other autoantibodies have been described against factors V, VII, XI
      and, rarely, factor XIII and prothrombin. New approaches in the management of
      autoimmune disease and, especially, methods to establish tolerance are in
      development.

PMID- 11844136
TI  - Rare acquired bleeding disorders.
AB  - Accurate diagnosis of the cause of bleeding is a prerequisite for determination
      of the optimal therapeutic response. Clinicians are generally aware of the more
      prevalent hemorrhagic syndromes but some rare acquired conditions are also of
      importance. In many of these, inhibitors of coagulation factors or of platelet
      adhesion/aggregation cause bleeding. These inhibitors are generally, but not
      always, immunoglobulins. In this review, the less common inhibitors of
      coagulation and hemostasis, as well as some important but rare nutritional,
      iatrogenic and disease associated hemorrhagic disorders, are described.

PMID- 11844138
TI  - West Mediterranean islands (Corsica, Balearic islands, Sardinia) and the Basque
      population: contribution of HLA class I molecular markers to their evolutionary
      history.
AB  - The genetic structure of Balearic islands (Corsica and Sardinia), situated on the
      same trans-Mediterranean maritime routes and having very similar histories, were
      compared and their position among the neighbouring Caucasian populations was
      inferred. For this purpose, three HLA loci (HLA-A, -B and -Cw) were typed at the
      DNA level in these populations and the allelic and haplotypic frequencies were
      estimated. Because previous studies have shown common genetic features in the
      Sardinians and Basques, HLA-Cw molecular typing was also performed in a sample of
      French Basques in order to establish the haplotypic structure of this population
      for a more accurate comparison with the three others. By its allelic composition,
      the Corsican population has an intermediate position between the two other
      islander populations. Its close relationship with the Sardinian population,
      however, was clearly revealed by the phylogenetic analysis which also suggests a
      proximity with eastern Mediterranean peoples, whereas the Balearic islands are
      more narrowly related to Spain and western Europe. Peculiarities were observed in
      the distributions of some common haplotypes in the populations of the islands
      that confirm the results of the phylogenetic analysis and could be related to
      their history. Noteworthy is the presence of the HLA-A30-Cw*0501-B18 haplotype at
      frequencies approximately 2% in Corsica and the Balearic islands, yet the
      estimated frequencies of this haplotype are much lower than in the Sardinian and
      Basque populations.

PMID- 11844139
TI  - Polymorphism in RANTES chemokine promoter affects extent of sarcoidosis in a
      Japanese population.
AB  - RANTES, a member of C-C chemokine, is known to be produced at sites of
      granulomatous reactions in the lung of sarcoidosis. RANTES is a potent eosinophil
      and lymphocyte attractant with particular preference for CD45RO+ T cells and
      eosinophils. Polymorphism of the RANTES promoter has recently been shown to be
      related to allergic and infectious diseases; atopic dermatitis, asthma, and
      polymyalgia rheumatica. Considering that this might affect sarcoidosis, we
      studied polymorphism of the RANTES gene in 114 patients with sarcoidosis and 136
      healthy control subjects. Their genotypes were determined using polymerase chain
      reaction (PCR) and restriction fragment length polymorphism (RFLP). Although no
      difference in the genotype distribution between healthy control subjects and
      sarcoidosis patients was identified, the difference in the frequencies of the
      patients with three or more organ involvement was significant (P<0.01) with the
      frequency of those in AA genotype being elevated (P<0.05). BAL findings in 48 out
      of 114 patients who underwent bronchoscopy were reviewed. The CD4/8 ratio of
      lymphocytes in bronchoalveolar lavage fluid in the patients with AA genotype was
      significantly increased (P<0.05). From the results, we suggest that in RANTES
      gene polymorphism the homozygous A allele might be a genetic risk factor for
      extent disease of sarcoidosis.

PMID- 11844140
TI  - HLA-AB typing by polymerase-chain reaction with sequence-specific primers: more
      accurate, less errors, and increased resolution compared to serological typing.
AB  - Until recently, serological typing has been the primary technique used for HLA
      class I analysis. But because of limitations, molecular-typing techniques have
      replaced or supplemented the microlymphocytotoxicity test. It has been assumed
      that HLA class I serological typing was more accurate than serological HLA-DR
      typing; the latter has been shown to have 10-25% errors. But several studies have
      shown that HLA-AB typing was poorer than expected, and error frequencies between
      5-25% were reported. This study systematically investigated the accuracy of HLA
      class I serological AB typing in healthy, bone-marrow registry donors,
      necrokidney donors, kidney-transplantation patients (on waiting lists), and
      haematological disorder patients. Genomic HLA class I typing, which uses
      polymerase-chain reaction with sequence-specific primers (PCR-SSP), gave
      discrepant results in 3-24% of the patients, compared to serological typings. The
      highest error rate (24%) was found among haematological disorder patients. Among
      the kidney waiting-list patients and necrokidney donors, 11% discrepancies were
      found. In the consecutively typed bone-marrow donors group, 3% errors were found.
      But among those with only one detected HLA-A specificity, 12% discrepancies were
      found, and among donors with only one detected HLA-B specificity, 19% errors were
      found. Based on these results, we recommend that patients with haematological
      disorders should be typed using genomic techniques. In investigations of bone
      marrow registry donors and kidney patients, in which only one serological
      specificity is found, additional typing by genomic methods should be done.

PMID- 11844141
TI  - High-resolution sequence-based typing strategy for HLA-DQA1 using SSP-PCR and
      subsequent genotyping analysis with novel spreadsheet program.
AB  - We present a new sequence-based typing (SBT) strategy for the polymorphic HLA
      DQA1 locus that is based on sequence-specific primer - polymerase chain reaction
      (SSP-PCR) amplification from genomic DNA. This method allows high-resolution
      genotyping in the second exon of the DQA1 gene. This gene presents a unique
      situation in which half of the known alleles contain an inframe three base pair
      deletion of codon 56. This deletion confounds direct SBT methodologies of
      heterozygous individuals containing both a deletion and nondeletion allele. The
      primary HLA haplotype associated with type 1 diabetes susceptibility is DR3/DR4.
      The DQA1 genotype for these two haplotypes are DQA1 *0501, a non-deletion allele
      and *0301, a deletion allele, thus creating a situation that cannot be resolved
      using a direct sequencing approach. Our group-specific SBT strategy isolates the
      deletion alleles from the nondeletion alleles, allowing them to be resolved by
      direct sequencing. Additionally, we present a novel spreadsheet program that
      accurately assigns the genotype of both homozygous and heterozygous persons.

PMID- 11844142
TI  - Polymorphism in the Y box controls level of cytokine-mediated expression of HLA
      DRB1 genes.
AB  - The HLA class II molecules play an important role in immune response. The quality
      of immune response is dependent not only on the polymorphisms in the class II
      molecules, but also on the level of their cell-surface expression. In fact, it
      has been demonstrated that differences in the level of expression of DRB1 and
      DRB3 genes restricted and activated distinct CD4+ T lymphocytes. We and others
      have previously described allelic polymorphisms in the upstream regulatory
      regions of DRB genes, which affected DNA-protein interactions and resulted in
      significantly different promoter strengths. We showed that polymorphisms in both
      the X1 and Y box motifs affect level of constitutive expression of DRB1 genes in
      the DR1, DR51 and DR53 haplotype groups. In the present study, we examined the
      effect polymorphisms in the X1 box and the Y box on the cytokine (interferon
      gamma (IFNgamma), tumor necrosis factor-alpha (TNFalpha) and granulocyte
      macrophage-colony-stimulating factor (GM-CSF))-mediated transcriptional
      activities of DRB1 promoters in these, i.e. DR1, DR51 and DR53, haplotype groups.
      The results demonstrate that the polymorphism in the X1 box does not affect
      cytokine-mediated strength of DRB1 gene promoters. In contrast, the polymorphism
      in the Y box, which affects the inverted CCAAT sequence, plays a dominant role on
      the cytokine-mediated transcriptional activity of DRB1 promoters.

PMID- 11844143
TI  - Linkage disequilibrium of HLA-A11 and A1 with one of the polymorphisms of the
      gamma-aminobutyric acid receptor type B.
AB  - The gamma-aminobutyric acid receptor type B 1 (GABA(B) R1) is located
      approximately at 200 kb telomeric to HLA-A on chromosome 6. It has 11 single
      nucleotide polymorphisms (SNPs). We studied the most common of its SNPs (T1974C)
      in a panel of 118 normal Caucasians from New England and 161 epileptic patients
      of Caucasian ancestry residing in USA. The frequency of the polymorphism did not
      differ between patients and controls. Here, we report that the allele C of this
      SNP in the GABA(B) R1 gene is in linkage disequilibrium with HLA-A11 (P<0.00001)
      and to a lesser extent with HLA-A1 (P<0.01).

PMID- 11844144
TI  - Cloning of rhesus monkey killer-cell Ig-like receptors (KIRs) from early
      pregnancy decidua.
AB  - To define the killer-cell Ig-like receptors (KIR) molecules expressed within the
      decidua in the rhesus monkey, an early pregnancy rhesus decidual library was
      screened with an oligonucleotide located within the KIR D2 domain. We obtained 26
      full-length clones which represented 11 mRNAs. The cDNAs encode proteins
      containing 2 or 3 Ig domains, and short or long cytoplasmic domains. The long
      domains contained immunotyrosine inhibitory motifs (ITIM) motifs indicating
      inhibitory function. Three clones contained single or dinucleotide deletions
      within the D1 domain, which would result in proteins truncated within this
      domain. Phylogenetic analysis of the Ig domains supports a D0 - D2 organization
      of rhesus KIR2DL4.1, similar to human KIR2DL4 and KIR2DL5. The rhesus KIR2DL4.1
      transcript contains a long cytoplasmic tail homologous with human KIR2DL4.

PMID- 11844145
TI  - MCP-1 promoter polymorphism in Spanish patients with systemic lupus
      erythematosus.
AB  - The possible role of the functional polymorphism located in the regulatory region
      of the monocyte chemoattractant protein-1 (MCP-1) gene in the susceptibility to
      systemic lupus erythematosus (SLE) was investigated. Two hundred and seventy-six
      SLE patients (among them, 99 with lupus nephritis and 55 with cutaneous
      vasculitis) and 194 ethnically matched healthy controls were included in the
      study. Genotyping for -2518 (A/G) MCP-1 gene polymorphism was performed by
      polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)
      analysis. No association between -2518 (A/G) MCP-1 polymorphism and
      susceptibility to SLE nor to lupus nephritis was found. However, a significant
      increase in the frequency of genotype AG and a decrease in the frequency of
      genotype AA were found among patients with cutaneous vasculitis (51% of AG vs.
      32% in individuals without cutaneous vasculitis; P=0.008, OR=2.2, 95% CI: 1.18
      4.25; and 47% of AA vs. 64%; P=0.03, OR=0.5, 95% CI: 0.27-0.96, respectively).
      These results indicate an association between the presence of G at position -2518
      in the MCP-1 promoter region and the presence of cutaneous vasculitis among
      patients with SLE. This polymorphism does not seem to influence the
      susceptibility to SLE nor the appearance of lupus nephritis. Further studies are
      necessary in order to elucidate the role of this polymorphism in the pathogenesis
      of other inflammatory autoimmune diseases.

PMID- 11844146
TI  - Seven single nucleotide substitutions in human Fc(gamma) receptor IIB gene.
AB  - Variation screening for the immunoglobulin G Fc receptor IIB (Fc(gamma)RIIB) gene
      was performed with the genomic DNA from 100 healthy Japanese subjects. We
      identified 3 non-synonymous and 2 synonymous substitutions and 2 single
      nucleotide polymorphisms in an intron region. These substitutions were found to
      be located in the ligand-binding domain and the intron, which might alter the
      function of Fc(gamma)RIIb.

PMID- 11844147
TI  - Identification and sequencing of the HLA-B*4106 allele.
AB  - We report a novel HLA-B*41 allele (HLA-B*4106) initially detected by an unusual
      sequence-specific oligonucleotide (SSO) hybridization pattern and identified by
      sequence-based HLA typing. Molecular cloning and sequencing determined that the
      new HLA-B allele was identical to the HLA-B*4101 in exon 2 and 3 except for a
      single nucleotide substitution in the exon 3 changing codon 204 from Glu to Gln
      (GAG-->CAG). In addition, intron 2 was identical to the published HLA-B*4104
      intron 2, except for the base 509 (C-->G).

PMID- 11844148
TI  - Identification of a novel allele HLA-B*7805 in a Japanese female.
AB  - A new HLA-B*78 allele, B*7805, was identified in a healthy Japanese female. The
      results of her serological HLA class I typing showed an unusual Bw4/Bw6 pattern
      with strongly positive reactivity to anti-Bw6, i.e. A24, -, B52, -, Bw4, Bw6. In
      DNA typing, she was typed as A*24, -, B*52, B*78-like, Cw1202, -, (Bw4, Bw6).
      Cloning and sequencing of exon 2 and exon 3 of her B locus genes revealed a new
      allele B*7805. The cloned B*7805 differed from B*78021 by three nucleotide
      substitutions in exon 2 at position 259 (A to G), 261 (C to G) and 272 (A to C),
      and contained sequences defining Bw6 motif in the region of codon 77 to 83.

PMID- 11844149
TI  - Infection, antimicrobial resistance, and newly emerging pathogens: the growing
      role of fungi.

PMID- 11844150
TI  - Pulmonary scedosporium infection following lung transplantation.
AB  - Infectious complications are frequent following lung transplantation.
      Tracheobronchial aspergillosis is the predominant fungal infection in these
      patients. Infections with Scedosporium apiospermium (Pseudoallescheria boydii)
      and Scedosporium prolificans (Scedosporium inflatum) have mainly been described
      in bone marrow transplant recipients and only occasionally in solid organ
      transplant recipients. We analysed risk factors, the clinical course and outcome
      of seven lung transplant recipients who developed pulmonary scedosporium
      infection. Scedosporium apiospermium was documented in bronchoalveolar lavage
      (BAL) of all seven and Scedosporium prolificans in the BAL of four of these
      patients. Scedosporium was detected 9-58 months after transplantation. Five of
      the seven patients had been treated for several months with itraconazole because
      of previous detection of aspergillus in BAL. All seven patients with scedosporium
      infection showed airway problems, including early ischemic airway stenosis in one
      and bronchiolitis obliterans syndrome in the other six patients. Combined
      treatment with itraconazole and fluconazole was not able to eradicate
      scedosporium. Four of the seven patients died with advanced bronchiolitis
      obliterans 3-35 months after the diagnosis of pulmonary scedosporium infection.
      Three patients are currently alive 3, 6 and 7 years after transplantation,
      showing persistent scedosporium infection. In conclusion, pulmonary scedosporium
      infection was seen in lung transplant recipients with structurally abnormal
      airways and under long-term therapy with itraconazole. Eradication of
      scedosporium proved difficult, but under combined treatment with itraconazole and
      fluconazole this opportunistic infection did not disseminate.

PMID- 11844152
TI  - Hospitalizations for fungal infections after renal transplantation in the United
      States.
AB  - Fungal infections in renal transplant recipients have not been studied in a
      national population. Therefore, 33,420 renal transplant recipients in the United
      States Renal Data System from 1 July 1994 to 30 June 1997 were analyzed in a
      retrospective registry study of hospitalized fungal infections (FI). FI were most
      commonly associated with secondary diagnoses of esophagitis (68, 23.9%),
      pneumonia (57, 19.8%), meningitis (23, 7.6%), and urinary tract infection (29,
      10.3%). Opportunistic organisms accounted for 95.4% of infections, led by
      candidiasis, aspergillosis, cryptococcosis, and zygomycosis. Most fungal
      infections (66%) had occurred by six months post-transplant, but only 22% by two
      months. In logistic regression analysis, end-stage renal disease due to diabetes,
      duration of pre-transplant dialysis, maintenance tacrolimus and allograft
      rejection were associated with FI. In Cox regression analysis, recipients with FI
      had a relative risk of mortality of 2.88 (95% CI=2.22-3.74) compared to all other
      recipients. Among FI, zygomycosis and aspergillosis were independently associated
      with both increased patient mortality and length of hospital stay. Most fungal
      infections in renal transplant recipients were opportunistic, occurred later than
      previously reported, and were associated with greatly decreased patient survival.
      Recipients with diabetes, prolonged pre-transplant dialysis, rejection, and
      tacrolimus immunosuppression should be considered high risk for FI.

PMID- 11844151
TI  - Sequence analysis of UL54 and UL97 genes and evaluation of antiviral
      susceptibility of human cytomegalovirus isolates obtained from kidney allograft
      recipients before and after treatment.
AB  - The frequency of infections caused by drug-resistant cytomegalovirus (CMV) in
      solid-organ transplant recipients is not known. Only a few resistant strains have
      been described in transplant recipients. Antiviral susceptibility to ganciclovir
      (GCV) and foscarnet (PFA) of CMV isolates from 24 renal transplant patients with
      CMV viremia and CMV disease before and after therapy were investigated by a solid
      phase ELISA. The CMV DNA polymerase (UL54) and viral phosphotransferase (UL97)
      genes were also sequenced. Ten patients did not receive antiviral treatment; five
      and nine patients were treated with PFA and GCV, respectively. No appearance of
      drug-resistant viruses was observed in the present study, but one isolate showed
      a reduced sensitivity to PFA after treatment with GCV. This finding could not be
      explained by the presence or development of mutations that have been associated
      with drug resistance in UL54. We found no evidence that short-term treatment of
      CMV with PFA- or GCV-induced resistance.

PMID- 11844154
TI  - Disseminated Mycobacterium avium-intracellulare in a kidney transplant recipient.

PMID- 11844153
TI  - NF-kappaB in transplantation: friend or foe?
AB  - NF-kappaB is an inducible nuclear transcription factor regulating the expression
      of many genes. NF-kappaB activation may function as a master switch in a variety
      of immune and inflammatory processes, including sepsis and transplant tolerance.
      In this review, we summarize features of NF-kappaB regulation, as well as
      describe its role in intracellular signal transduction pathways. Subsequently, we
      concentrate on the role of NF-kappaB in the field of organ transplantation and
      the role of NF-kappaB in organ ischemia/reperfusion injury and graft rejection.
      Finally, potential therapeutic strategies are discussed to modify NF-kappaB
      activity with certain immunosuppression medications, including cyclosporine,
      tacrolimus, and glucocorticoids.

PMID- 11844156
TI  - Relapsing Exophiala jeanselmei phaeohyphomycosis in a lung-transplant patient.
AB  - Dematiaceous fungi are a cause of a variety of human infections, including
      phaeohyphomycosis, that may affect patients with solid organ or bone marrow
      transplants. Exophiala jeanselmei, the most common cause of the pheomycotic
      cyst/subcutaneous phaeohyphomycosis in the United States, has been shown to cause
      disease in transplant recipients. We report a lung-transplant patient with
      relapsing and invasive E. jeanselmei phaeohyphomycosis, who previously had a
      pheomycotic cyst excised and treated with oral fluconazole. The patient was
      subsequently treated with re-excision and an 8-month course of oral itraconazole
      without relapse as to date.

PMID- 11844155
TI  - Cavernous sinus thrombosis caused by zygomycosis after unrelated bone marrow
      transplantation.
AB  - Invasive zygomycosis is a devastating fungal infection occurring as an
      opportunistic infection after bone marrow transplantation (BMT). Sinusitis can
      lead to fungal infection in immunosuppressed patients, and cavernous sinus
      thrombosis, an uncommon condition in immunocompetent patients, typically follows
      an infection involving the medial third of the face, nose, or paranasal sinuses.
      Patients undergoing unrelated-donor BMT (UD-BMT) are prone to develop life
      threatening infections because of poor recovery of cellular immunity. Despite
      adequate clinical evaluation and treatment, the prognosis of patients with
      invasive fungal infections is dismal, especially when intracerebral structures
      are affected. We describe a case of a patient who underwent an UD-BMT and
      developed cavernous sinus thrombosis after sinusitis due to zygomycosis.
      Moreover, he also had disseminated fungal (Zygomycetes and Aspergillus) and viral
      (cytomegalovirus and adenovirus) infections.

PMID- 11844157
TI  - Oligohydramnios: use and misuse in clinical management.

PMID- 11844158
TI  - Controversies in cleft lip and palate management.

PMID- 11844159
TI  - Fetal cleft lip and palate: sonographic diagnosis, chromosomal abnormalities,
      associated anomalies and postnatal outcome in 70 fetuses.
AB  - OBJECTIVE: The aim of this study was to determine the relationship between facial
      clefts, associated malformations and chromosomal abnormalities. STUDY DESIGN:
      Sonograms of 70 fetuses with cleft lip with or without cleft palate were
      prospectively and retrospectively evaluated in our tertiary referral center for
      the nature of the cleft lip or palate and for the nature of the associated
      anomalies. Additionally, karyotyping was performed in 63 of the 70 patients
      (90%). RESULTS: The frequency of additional anomalies and the mortality rate in
      this selected population varied with the type of cleft. None of the fetuses
      presenting an isolated cleft lip had additional anomalies and all survived. All
      fetuses presenting a median facial cleft had concurrent anomalies (particularly
      of the central nervous system (90%)) and a fatal outcome. Associated defects were
      more frequent in fetuses with bilateral clefts (72%) than in those with
      unilateral clefts (48%). Fetuses with a unilateral cleft lip with or without
      cleft palate had a better survival rate (52%) than those with a bilateral cleft
      lip with or without cleft palate (35%). The frequency and type of chromosomal
      abnormalities varied with the type of cleft. The highest rate of chromosomal
      abnormalities was found in fetuses with median clefts (82%). CONCLUSIONS:
      Although no conclusions regarding the prevalence of chromosomal or other
      anomalies in patients with a cleft lip with or without cleft palate in the
      general population could be drawn, the study revealed a strong relationship
      between the type of facial cleft, associated malformations, chromosomal
      abnormalities and fetal outcome.

PMID- 11844160
TI  - The accuracy of antenatal ultrasound in the detection of facial clefts in a low
      risk screening population.
AB  - OBJECTIVES: To evaluate the accuracy of prenatal ultrasound in the detection of
      facial clefts in a low-risk screening population and to report on the outcome of
      these pregnancies. DESIGN: We retrospectively reviewed antenatal ultrasound
      records from the obstetric ultrasound department, postnatal records from the
      regional craniofacial unit and autopsy reports of fetuses over 16 weeks'
      gestational age from the regional pathology department over a 5-year period (1993
      97). Cross-referencing between the three data sets identified all cases of facial
      clefts. RESULTS: Out of 23 577 live and still births, 30 had facial clefts; four
      were excluded from the study. Of the remaining 26 cases, 10 had associated major
      anomalies. There were 19 live births and seven terminations. Six of the seven
      terminations had other major abnormalities. Our detection rate for cleft lip and
      palate was 93% and the detection rate for isolated cleft palate was 22%. Isolated
      cleft lip was detected in 67% of cases. The overall detection rate for facial
      clefts was 65%. CONCLUSION: From our results and a review of the literature it is
      clear that before standards can be set we need to define which facial clefts are
      sonographically demonstrable. Our data provide information for effective
      counseling and setting of standards for clinical practice.

PMID- 11844161
TI  - Outcome of fetal talipes following in utero sonographic diagnosis.
AB  - OBJECTIVES: To examine the association between fetal talipes and other defects,
      and outcome in relation to postnatal surgery. METHODS: All cases of talipes
      presenting to the fetal medicine unit between 1993 and 1998 and cases of isolated
      talipes presenting to the ultrasound department between 1991 and 1998 were
      examined. The infants were followed-up to determine the number of cases that had
      structural or positional talipes and the number of cases requiring surgery.
      RESULTS: There were 76 cases, 59 of which attended the fetal medicine unit and 17
      the ultrasound department. Postnatal follow-up details were available in 31 of
      the 40 live births. There were three neonates with unilateral talipes at birth
      who were thought to have bilateral talipes on prenatal ultrasound and one neonate
      had bilateral talipes at birth who had been thought to have unilateral talipes
      prenatally. In two (6.4%) neonates in whom talipes was not confirmed at birth the
      abnormality was diagnosed prenatally. Of the 29 neonates with confirmed talipes
      at birth, the defect was structural in 26 (90%) cases and positional in three.
      Surgery was necessary in 21 (72%) of the 29 cases and 18 (86%) of those
      undergoing surgery required only one operation. When live births with associated
      anomalies were excluded, there were 24 cases with confirmed isolated talipes and
      18 (75%) required surgery. CONCLUSIONS: This study provides long-term outcome
      data which can be used to complement current prenatal counseling and shows that
      in cases of fetal talipes diagnosed prenatally, 90% have a structural rather than
      a positional deformity. For isolated talipes three quarters of children will
      require surgery and in the majority of cases only one operation on the foot is
      necessary. Parents should be made aware of the small possibility of a false
      positive diagnosis and discrepancy between the ultrasound and postnatal diagnoses
      of laterality.

PMID- 11844162
TI  - Multicenter screening for pre-eclampsia and fetal growth restriction by
      transvaginal uterine artery Doppler at 23 weeks of gestation.
AB  - OBJECTIVE: To determine the value of transvaginal color Doppler assessment of the
      uterine arteries at 23 weeks of gestation in predicting the subsequent
      development of pre-eclampsia and fetal growth restriction. PATIENTS AND METHODS:
      Women with singleton pregnancies attending for routine ultrasound examination at
      23 weeks in any one of seven hospitals underwent Doppler assessment of the
      uterine arteries. The presence of an early diastolic notch in the waveform was
      noted, and the mean pulsatility index of the two arteries was calculated.
      Screening characteristics in the prediction of pre-eclampsia and the delivery of
      a low birth-weight infant were calculated. RESULTS: Doppler examination of the
      uterine arteries was attempted in 8335 consecutive singleton pregnancies,
      satisfactory waveforms were obtained from both vessels in 8202 (98.4%) cases and
      complete outcome data were available in 7851 (95.7%) of these. The mean
      gestational age was 23 (range, 22-24) weeks. The mean uterine artery pulsatility
      index did not change significantly with gestation (r = -0.0078; P = 0.483); the
      median value was 1.04 and the 95th centile was 1.63. In 9.3% of cases early
      diastolic notches in the waveform from both uterine arteries were present and in
      an additional 11.1% of cases there were notches unilaterally. Pre-eclampsia with
      fetal growth restriction occurred in 42 (0.5%) cases, pre-eclampsia without fetal
      growth restriction in 71 (0.9%) and fetal growth restriction without pre
      eclampsia in 698 (8.9%). The sensitivity of increased pulsatility index above the
      95th centile (1.63) for pre-eclampsia with fetal growth restriction was 69%, for
      pre-eclampsia without fetal growth restriction was 24%, for fetal growth
      restriction without pre-eclampsia was 13%, for pre-eclampsia irrespective of
      fetal growth restriction was 41% and for fetal growth restriction irrespective of
      pre-eclampsia was 16%. The sensitivity of fetal growth restriction defined by the
      5th rather than the 10th centile was higher (19% vs. 16%). The sensitivity for
      both pre-eclampsia and fetal growth restriction was inversely related to the
      gestational age at delivery; when delivery occurred before 32 weeks, the
      sensitivity for all cases of pre-eclampsia with fetal growth restriction, pre
      eclampsia without fetal growth restriction and fetal growth restriction without
      pre-eclampsia increased to 93%, 80% and 56%, respectively. The sensitivity of
      bilateral notches in predicting pre-eclampsia and/or fetal growth restriction was
      similar to that of increased pulsatility index but the screen-positive rate with
      notches (9.3%) was much higher than that with increased pulsatility index (5.1%).
      CONCLUSIONS: A one-stage color Doppler screening program at 23 weeks identifies
      most women who subsequently develop severe pre-eclampsia and/or fetal growth
      restriction.

PMID- 11844163
TI  - Maternal diastolic function in asymptomatic pregnant women with bilateral
      notching of the uterine artery waveform at 24 weeks' gestation: a pilot study.
AB  - OBJECTIVE: To study second-trimester maternal cardiac adaptation in asymptomatic
      patients at risk, on the basis of abnormal uterine artery Doppler, for the
      development of gestational hypertension or having a small-for-gestational age
      fetus. Fetal and maternal outcomes were verified at the end of pregnancy.
      METHODS: Thirty-six normotensive women with abnormal uterine artery waveforms
      underwent maternal echocardiographic examination at 24 weeks' gestation. RESULTS:
      Twenty-one women (58.3%) subsequently showed normal outcome; 12 patients
      developed gestational hypertension (33.3%) and three (8.3%) had small-for
      gestational age newborns. Left ventricular outflow tract, left ventricular
      diastolic dimensions and atrial and ventricular function were significantly lower
      in the pathological outcome group. Diastolic function parameters were
      significantly different between the two groups: peak mitral E-wave and A-wave and
      A-wave duration showed lower values in the pathological outcome group.
      Isovolumetric relaxation time of the left ventricle was significantly longer in
      the pathological outcome group. The prevalence of an altered geometric pattern
      was 14.3% (3/21) in the normal and 80% (12/15) in the pathological outcome groups
      (P < 0.001). CONCLUSIONS: Women who subsequently develop a complication of
      pregnancy tend to display abnormal cardiac adaptation. An abnormal placentation
      process, expressed by an elevated resistance index and the presence of notches in
      the uterine artery waveform, are likely to cause an adaptative mechanism
      involving the whole cardiovascular system. A pathological outcome of pregnancy is
      associated with the failure of this process.

PMID- 11844164
TI  - Repeatability of measurement of uterine artery pulsatility index using
      transvaginal color Doppler.
AB  - OBJECTIVE: To assess the repeatability of measuring the pulsatility index of the
      uterine arteries using transvaginal color Doppler at 23 weeks of gestation.
      PATIENTS AND METHODS: The pulsatility index was measured in 100 women with
      singleton pregnancies attending for routine transvaginal Doppler examination of
      the uterine arteries at 23 weeks. To assess the repeatability of different
      components of variability, six measurements of the uterine artery pulsatility
      index were made on one of the uterine arteries in each patient. RESULTS: Six
      measurements of the pulsatility index were successfully measured in all 100
      patients, resulting in a total of 600 measurements. The repeatability was
      unrelated to the pulsatility index. On 95% of occasions the intraobserver,
      interobserver and waveform tracing repeatability was less than 0.24, 0.27 and
      0.14, respectively. CONCLUSIONS: Measurement of the pulsatility index using
      transvaginal color Doppler is highly reproducible when the examination is carried
      out by well-trained operators.

PMID- 11844165
TI  - Maternal left ventricular mass and diastolic function during pregnancy.
AB  - OBJECTIVE: To evaluate changes in left ventricular mass and diastolic function
      during normal pregnancy. METHODS: This was a cross-sectional study of 125
      pregnant women at 9-42 weeks of gestation and 19 non-pregnant female controls.
      Two-dimensional and M-mode echocardiography of the maternal left ventricle and
      left atrium was performed. RESULTS: During pregnancy left ventricular mass
      increased by 52%. There was an increase in left ventricular end-diastolic and end
      systolic diameters (12% and 20%, respectively), left ventricular posterior wall
      diameter during diastole and systole (22% and 13%, respectively) and left
      intraventricular septum during diastole and systole (15% and 19%, respectively).
      Mitral valve A-wave maximum velocity increased during pregnancy by 19%, while
      mitral valve E-wave maximum velocity and the ratio of E-wave/A-wave velocities
      increased early in pregnancy by about 14% and 6%, respectively, with a subsequent
      decline to 4% and 10%, respectively, below non-pregnant levels. CONCLUSION: Left
      ventricular mass increases during pregnancy, while left ventricular diastolic
      function, as demonstrated by the changes in mitral valve flow velocities,
      increases in the first two trimesters but declines in the third trimester.

PMID- 11844166
TI  - Maternal left ventricular transverse and long-axis systolic function during
      pregnancy.
AB  - OBJECTIVES: Circumferential fiber shortening has been the dominant basis for
      conventional analysis by echocardiography of left ventricular systolic function
      during pregnancy. Results in the literature have been conflicting due mainly to
      the fact that geometric assumptions for the calculation of these indices are made
      that may not be valid due to changes in left ventricular shape during pregnancy.
      Left ventricular long-axis displacement is expected to be a useful index of
      systolic function, independent of the changes in left ventricular geometry. The
      aim of this study was to compare circumferential to long-axis shortening during
      left ventricular contraction in pregnant women. METHODS: This was a cross
      sectional study of 125 pregnant women at 9-42 weeks of gestation and 19 non
      pregnant female controls. Two-dimensional and M-mode echocardiography of the left
      ventricle was performed including measurement of left ventricular long-axis
      displacement and activation time on the lateral, septal, anterior and inferior
      sides of the mitral annulus. Activation time was assessed as the time from the
      start of the Q-wave of the electrocardiogram to the onset of left ventricular
      long-axis shortening. RESULTS: Mean arterial pressure and activation time
      decreased during pregnancy, reaching a nadir at about 19 weeks' gestational age
      of 4% and 13%, respectively, below non-pregnant values; they subsequently
      increased towards term. Left ventricular long-axis displacement mirrored the
      changes in mean arterial pressure and activation time and increased with
      gestational age at all four sites of the atrioventricular plane reaching a peak
      at about 23 weeks (+ 12% compared to non-pregnant levels). The ejection fraction
      and fractional shortening remained stable until 30 and 32 weeks, respectively,
      and then decreased towards term. CONCLUSION: Changes in left ventricular long
      axis performance during pregnancy occur earlier than do measures of transverse
      function.

PMID- 11844167
TI  - Comparison between two- and three-dimensional ultrasound measurements of nuchal
      translucency.
AB  - OBJECTIVE: Fetal nuchal translucency measurement has been introduced as a
      screening test for the calculation of risk of chromosomal abnormalities. The
      purpose of this study was to investigate: (1) the feasibility of obtaining nuchal
      translucency measurements using three-dimensional ultrasound; (2) whether three
      dimensional ultrasound could improve and facilitate the required repeated
      measurements of nuchal translucency; (3) the correlation between two- and three
      dimensional nuchal translucency measurement values. SUBJECTS AND METHODS: Between
      September 1999 and May 2000, in a prospective cohort study, 229 unselected
      pregnant women with a mean age of 34.6 (range, 20-46) years were examined. The
      mean fetal crown-rump length was 64.3 (range, 45-84) mm. Nuchal translucency
      thickness was measured first by two- and then by three-dimensional ultrasound in
      two planes (three-dimensional mid-sagittal and three-dimensional transverse). An
      attempt was made to repeat each nuchal translucency measurement three times
      (totalling nine measurements per patient) and the means of the two- and three
      dimensional measurements were compared. The majority (95%) of the measurements
      were made transabdominally and 5% were made transvaginally. The time limit for
      each examination was 20 min. RESULTS: With the two-dimensional method, nuchal
      translucency could be measured in 96.8% of cases. Of these, three measurements
      could be obtained in 51.7%, two in 23.2% and only one in 25.1%. The three
      dimensional examination was successful in 98.6% of cases. Of these, three
      measurements could be obtained in 60%, two in 22.8% and one in 17.2%.
      Transvaginally, all examinations were successful. The main reason for the failure
      of two-dimensional ultrasound was the fetal position, which in some cases
      precluded the distinction between fetal skin and amnion or the uterine wall.
      Using two-dimensional ultrasound, 6.3% of the cases of measurement failure were
      due to an inability to differentiate clearly between fetal skin and amnion,
      whilst the equivalent value for the three-dimensional method was only 3.3%. For
      the three-dimensional technique, fetal movement was the main reason for failure.
      The mean time for both methods was similar (9 min and 10 min for two- and three
      dimensional ultrasound, respectively) and the correlation between the
      measurements obtained by the two- and three-dimensional techniques was very high
      (r = 0.97). CONCLUSION: The number of fetuses in which nuchal translucency could
      be measured tended to be higher with three-dimensional ultrasound, although the
      difference was not statistically significant. The possibility of rotating a
      stored volume and inspecting it in three orthogonal planes makes three
      dimensional ultrasound a useful tool for nuchal translucency measurements,
      especially in doubtful cases.

PMID- 11844168
TI  - Measurement of fetal nuchal translucency thickness by three-dimensional
      ultrasound.
AB  - OBJECTIVE: To investigate the feasibility and repeatability of nuchal
      translucency thickness measurement using three-dimensional ultrasound. METHODS:
      Forty consecutive women with uncomplicated singleton pregnancies attending for
      Down syndrome screening at 11-14 weeks' gestation were included in this
      prospective crossover trial. Nuchal translucency thickness was measured using
      both two-dimensional and three-dimensional ultrasound. In each case two three
      dimensional volumes were recorded and then examined by using the technique of
      planar reformatted sections. The initial plane of the first volume always
      contained a clear image of the nuchal region ('sagittal volume'), whilst the
      initial plane of the second volume was selected randomly regardless of fetal
      position ('random volume'). The repeatability of nuchal translucency measurement
      was examined by constructing a scatter diagram of the difference between the
      measurements plotted against the mean of two readings. RESULTS: Nuchal
      translucency measurements could be repeated in 38/40 (95%) sagittal volumes and
      24/40 (60%) random volumes. The mean difference between two-dimensional
      measurements and those obtained by reslicing of sagittal three-dimensional
      volumes was -0.097 mm (95% limits of agreement from -0.481 to 0.675) and 0.225 mm
      (95% limits of agreement from -0.369 to 0.819) when random volumes were examined.
      CONCLUSIONS: Reslicing of stored three-dimensional volumes can be used to
      replicate nuchal translucency measurements only when nuchal skin can also be
      clearly seen on two-dimensional ultrasound.

PMID- 11844169
TI  - A prospective longitudinal study of growth velocity in twin pregnancy.
AB  - OBJECTIVES: Fundamental research into the growth of twins is lacking. Twin growth
      in utero is commonly assumed to follow similar patterns of growth as that of
      singletons. This preliminary descriptive study on twin pregnancy aimed to define
      growth velocity as gestation advances, and to study if twin order, fetal sex,
      zygosity and chorionicity have any relationship to growth velocity. METHODS: One
      hundred and sixty-two women with twin pregnancies had an ultrasound examination
      at fortnightly intervals from 16 weeks until delivery. Fetal measurements of
      biparietal diameter, abdominal circumference and femur length were performed at
      each examination. Growth velocity for each parameter was defined as the
      difference in measurements for that parameter divided by the time interval
      between measurements. Postnatally, zygosity and chorionicity were determined by
      genetic fingerprinting and inspection of the placenta, respectively. RESULTS:
      Growth velocity for all parameters decreased as gestation advanced, with the
      downward trend more noticeable after 32 weeks. Maximum and minimum growth
      occurred at 22-23 weeks and 36-37 weeks, respectively. Maximum and minimum growth
      velocities for the abdominal circumference were 1.7 and 0.8 cm/week,
      respectively. Birth order, fetal sex, chorionicity and zygosity were not related
      to growth velocity. CONCLUSIONS: These preliminary results suggest that growth
      velocity in twins decreases after 32 weeks' gestation. It appears that growth
      velocity is independent of birth order, fetal sex, chorionicity and zygosity.

PMID- 11844170
TI  - Crown-rump lengths in missed miscarriages and trisomy 21.
AB  - OBJECTIVES: To compare crown-rump lengths with karyotypes of missed miscarried
      fetuses and to determine a relationship between crown-rump length and trisomy 21.
      STUDY DESIGN: Chorionic villus sampling was performed on 129 consecutive missed
      miscarriages between 10 and 12 weeks by last menstrual period in patients >or= 35
      years of age. Crown-rump length was correlated with the karyotype. Statistical
      analysis was performed using Student's t-test. RESULTS: Twenty-one of 129 missed
      miscarriages involved fetuses affected by trisomy 21. The crown-rump length was <
      22 mm in 77% of missed miscarriages. Using a crown-rump length of >or= 22 mm for
      the prediction of trisomy 21 had a sensitivity of 86%, specificity of 89%,
      positive predictive value of 60% and negative predictive value of 97%. At 10-12
      weeks, the crown-rump lengths of missed miscarried fetuses with trisomy 21 was
      significantly larger (P <or= 0.0001) than that of the population average of
      missed miscarried fetuses. CONCLUSION: In women >or= 35 years of age, with a
      missed miscarriage, in whom pregnancies reached >or= 10 weeks from the last
      menstrual period, a fetal crown-rump length of >or= 22 mm has a high probability
      that the etiology of the loss will be secondary to trisomy 21.

PMID- 11844171
TI  - Ultrasonic evaluation of the uterus and uterine cavity after normal, vaginal
      delivery.
AB  - OBJECTIVE: To describe uterine and uterine cavity changes throughout the
      puerperium, as revealed by ultrasound. METHODS: This was a prospective,
      longitudinal study in which 42 women with uncomplicated vaginal term deliveries
      were examined serially by ultrasound on postpartum days 1, 3, 7, 14, 28 and 56.
      The first four examinations were performed transabdominally and the last two
      transvaginally. The involution process of the uterus was assessed by measuring
      the anteroposterior diameter of the uterus and uterine cavity. Morphological
      findings were recorded. The influence on the involution process of parity, breast
      feeding, maternal smoking and infant's birth weight were also evaluated. RESULTS:
      The maximum anteroposterior diameter of the uterus diminished substantially and
      progressively from 92.0 mm on day 1 postpartum to 38.9 mm on day 56. The maximum
      anteroposterior diameter of the uterine cavity diminished from 15.8 mm on day 1
      to 4.0 mm on day 56. However, the anteroposterior diameter of the uterine cavity,
      5 cm from the fundus, typically increased on days 7 and 14 postpartum. The
      position of the uterus and the shape and the appearance of the cavity change in a
      unique way during the normal puerperium. The uterus was most often retroverted
      and empty in the early puerperium. Fluid and debris in the whole cavity were seen
      in the middle part of the puerperium. In late puerperium the cavity was empty and
      appeared as a thin white line. Endometrial gas was occasionally visualized. No
      correlation was found between the involution of the uterus and parity, breast
      feeding and the infant's birth weight. CONCLUSION: Transabdominal sonography is
      suitable for examination of the uterus during the first 14 days postpartum but
      from day 28 the transvaginal route is preferable. The uterine body and position,
      as well as the cavity, are easy to examine by ultrasound. Accumulation of fluid
      and debris in the uterine cavity is a common and insignificant finding of the
      involuting uterus. It is located in the cervical area in the early puerperium and
      in the whole uterine cavity in the middle part of the puerperium. Findings from
      uncomplicated vaginal deliveries are needed as a reference when the diagnostic
      efficacy of ultrasound for pathological conditions is to be tested.

PMID- 11844172
TI  - Rebleeding and endometrial growth in women with postmenopausal bleeding and
      endometrial thickness < 5 mm managed by dilatation and curettage or ultrasound
      follow-up: a randomized controlled study.
AB  - OBJECTIVE: To compare the frequency of rebleeding and endometrial growth during a
      12-month follow-up period between women with postmenopausal bleeding and an
      endometrial thickness < 5 mm managed by dilatation and curettage, and those
      managed by ultrasound follow-up. DESIGN: Consecutive women with postmenopausal
      bleeding and an endometrial thickness < 5 mm were randomized to ultrasound follow
      up after 3, 6, and 12 months (n = 48) or to primary dilatation and curettage with
      ultrasound follow-up at 12 months (n = 49). At all follow-up examinations, the
      endometrial thickness was measured and the women were asked about rebleeding. The
      endometrium was sampled at the 12-month examination, if sampling had not been
      performed previously because of rebleeding or endometrial growth. RESULTS:
      Rebleeding was reported by 33% (16/48) of the women in the ultrasound group and
      by 21% (10/48) of those in the dilatation and curettage group (P = 0.17).
      Endometrial growth to >or= 5 mm was found in 21% (10/48) of the women in the
      ultrasound group and in 10% (5/48) of those in the dilatation and curettage group
      (P = 0.16). No endometrial pathology was found in women with isolated rebleeding.
      Endometrial pathology during follow-up was found more often in women with
      endometrial growth than in those without (33% vs. 4%; P = 0.008). CONCLUSION:
      Rebleeding and endometrial growth are common during a follow-up period of 12
      months in women with postmenopausal bleeding and an endometrial thickness < 5 mm,
      irrespective of whether or not dilatation and curettage is primarily carried out.
      If these women are managed by ultrasound follow-up, endometrial sampling should
      be performed if the endometrium grows, but not necessarily in the case of
      rebleeding without endometrial growth.

PMID- 11844174
TI  - Ultrasound in the quantification of female pelvic organ prolapse.
AB  - OBJECTIVES: To evaluate the use of ultrasound in the quantification of prolapse
      and compare findings with clinical assessments obtained in a blind study.
      METHODS: In a prospective comparative clinical study, 145 patients referred for
      urogynecological assessment were examined clinically by one operator and by
      translabial ultrasound by another operator. RESULTS: Clinical staging and
      International Continence Society coordinates were obtained for all 145 patients,
      as were ultrasound coordinates for descent of the anterior and posterior vaginal
      walls. Eighteen percent of the uteri of those women who had not had a
      hysterectomy in the past could not be seen; none of these women suffered from
      uterine prolapse clinically. Correlation with the prolapse assessment system
      recently endorsed by the International Continence Society was good (r = 0.77 for
      uterine prolapse, r = 0.72 for anterior vaginal wall and r = 0.53 for posterior
      vaginal wall descent). CONCLUSIONS: This study demonstrates that translabial
      ultrasound can be used to quantify female pelvic organ prolapse. Correlation with
      the International Continence Society prolapse assessment system is good. The
      method may be particularly suitable for objective outcome assessment after
      surgical intervention.

PMID- 11844173
TI  - Doppler study of arterial and venous intraovarian blood flow in stimulated
      cycles.
AB  - OBJECTIVE: To evaluate arterial and venous intraovarian blood flow in follicle
      stimulating hormone-stimulated cycles. SUBJECTS AND METHODS: This was a
      prospective study of 76 follicle stimulating hormone-stimulated cycles carried
      out in 39 infertile patients who were included in a timed intercourse or
      intrauterine insemination program in a referral center for assisted reproduction.
      Transvaginal color and pulsed Doppler measurements of the follicular and luteal
      phase resistance index, pulsatility index, peak systolic velocity and maximum
      venous velocity were made and serum progesterone levels during the mid-luteal
      phase were recorded. Velocimetric parameters were established and then used to
      classify ovarian function as having a normal ovulatory cycle, or a cycle in which
      there was either luteal phase deficiency or a luteinized unruptured follicle.
      RESULTS: In 52 normal ovulatory cycles, the luteal phase peak systolic and
      maximum venous velocities were significantly higher and resistance and
      pulsatility indices were significantly lower than those found in the follicular
      phase. In 15 women with luteal phase deficiency we did not find any differences
      in arterial velocimetric parameters when compared with normal ovulatory cycles.
      However, luteal phase maximum venous velocities were lower in the luteal phase
      deficiency cycles and there was a significant correlation between luteal phase
      maximum venous velocity and serum progesterone levels (r = 0.36). Luteinized
      unruptured follicle cycles (n = 9) did not show significant changes during the
      ovarian cycle and no 'luteal conversion' of the Doppler signal was identified.
      CONCLUSIONS: Follicle stimulating hormone-stimulated cycles in infertile patients
      can have a high percentage of abnormal functional responses that can be diagnosed
      only by sonographic assessment, Doppler and the appropriate hormonal follow-up.
      Arterial and venous intraovarian blood flow remain unaltered during luteinized
      unruptured follicle cycles and serum progesterone levels correlated with luteal
      phase maximum venous velocity, which makes Doppler a potentially useful non
      invasive test to assess ovulation and luteal function.

PMID- 11844175
TI  - Color Doppler sonography of the lateral thoracic (breast-feeding) arteries: a new
      approach to the diagnosis of breast disease?
AB  - OBJECTIVE: The main arteries to the breast are the lateral thoracic artery and to
      a lesser extent the internal thoracic artery. In this prospective open diagnostic
      study involving 94 women, we compared the intraindividual differences of Doppler
      indices in the lateral thoracic (breast-feeding) artery of breasts affected by
      cancer with those unaffected by disease. METHODS: Sixty-seven consecutive
      patients were recruited from an outpatient unit for breast surgery and 27
      volunteers were studied who were known to be without any breast disease
      (controls). In each patient we attempted to obtain Doppler indices from the
      lateral thoracic artery of both breasts. The difference in Doppler indices in
      each individual was assessed and statistical analysis was performed to assess
      whether these differences were significantly altered in women with cancer
      compared to healthy women. RESULTS: Lateral thoracic arteries could be visualized
      in 88% of the study population. Significantly lower values for pulsatility and
      resistance indices and systolic/diastolic ratios were obtained in the lateral
      thoracic arteries of breasts affected by cancer as compared to the contralateral
      breasts (1.73 +/- 0.39 vs. 2.05 +/- 0.47, P = 0.003; 0.78 +/- 0.06 vs. 0.84 +/-
      0.06, P < 0.0001; 4.71 +/- 1.24 vs. 6.75 +/- 3.38, P = 0.0008, respectively).
      Using the intraindividual difference of pulsatility index, resistance index and
      systolic/diastolic ratio to screen for malignancy, sensitivities for breast
      cancer of 78%, 85% and 83%, respectively, were achieved. Depending on the cut-off
      level, specificity reached 94%. CONCLUSION: The intraindividual difference in
      Doppler indices in women with breast cancer may be a useful test for the
      diagnosis of breast lesions.

PMID- 11844176
TI  - Ultrasound-guided mammotome vacuum biopsy for the diagnosis of impalpable breast
      lesions.
AB  - OBJECTIVES: To assess the diagnostic accuracy of ultrasound-guided mammotome
      vacuum biopsy in impalpable breast lesions. METHODS: Seventy-three patients who
      presented with impalpable breast lesions that were suspicious for malignancy at
      mammography and/or sonography were included in the study. In the first instance
      the women underwent ultrasound-guided fine-needle aspiration cytology, then, 3
      days later, histological biopsy with an ultrasound-guided mammotome device. The
      patients with both cytological and histological diagnoses of malignancy underwent
      surgery; those with a negative (for malignancy) cytological diagnosis, but with a
      histological diagnosis of atypical hyperplasia or sclerosing adenosis, underwent
      surgical biopsy. RESULTS: The diagnostic accuracy of fine-needle aspiration
      cytology was 67.2%; the sensitivity was 86.7%, the specificity was 48.4%, the
      negative predictive value was 78.9% and the positive predictive value was 61.9%.
      In comparison, the diagnostic accuracy of histological sampling by mammotome
      vacuum biopsy was 97.3%; the sensitivity was 94.7%, the specificity was 100%, the
      negative predictive value was 94.6% and the positive predictive value was 100%.
      Thus there was a statistically significant difference in diagnostic accuracy
      between fine-needle aspiration cytology and mammotome vacuum biopsy (67.2% vs.
      97.3%; chi2 test, P < 0.001). The 2.7% (2/73) failure rate of mammotome biopsy
      was likely to be due to an error in the positioning of the needle. The subsequent
      surgical biopsy proved that two cases, negative for malignancy by mammotome
      biopsy, were in fact malignant. CONCLUSIONS: Our data confirm the value of
      sonography for the diagnosis of breast carcinoma in the preclinical phase and the
      efficacy of ultrasound sampling using a mammotome device to confirm the diagnosis
      in impalpable breast lesions.

PMID- 11844177
TI  - Assessment of Fallopian tube patency by HyCoSy: comparison of a positive contrast
      agent with saline solution.
AB  - OBJECTIVE: To compare the efficiency of air-filled albumin microspheres (Infoson)
      with saline solution in determining Fallopian tube patency during hysterosalpingo
      contrast sonography (HyCoSy). METHODS: This was a prospective randomized
      multicenter study with a sequential design. Over a 10-month period, 23 patients
      (mean age, 33 years) referred for infertility were examined by HyCoSy (saline or
      Infoson) before conventional hysterosalpingography (Iopamiron 370), performed
      during the same session. Contrast agents were administered through a 5-F Ackrad
      balloon catheter inserted transcervically into the uterine cavity. HyCoSy was
      performed with a 7-MHz transvaginal probe using both B-mode and color Doppler,
      and tubal patency was demonstrated by the appearance of contrast agent in the
      peritoneal cavity near the ovaries. Data were registered for each patient during
      the examination and the results were monitored by sequential analysis. RESULTS:
      Mean volumes of contrast injections were 35.3 mL of saline, 14.4 mL of Infoson,
      and 13.8 mL of Iopamiron 370. Infoson-enhanced HyCoSy provided a significantly
      larger (P = 0.006) number of correct diagnoses (20/22 Fallopian tubes) than did
      saline HyCoSy (12/24 Fallopian tubes), and the same number as that achieved by
      hysterosalpingography. CONCLUSION: A positive ultrasound contrast agent appears
      to be more efficient than saline solution at determining Fallopian tube patency
      in infertile women by means of HyCoSy, and as efficient as an iodinated contrast
      agent in the same population explored by HSG. HyCoSy could be used to screen
      infertile women, thereby avoiding the use of iodinated contrast medium and
      exposure to ionizing radiation during conventional HSG in patients with patent
      Fallopian tubes.

PMID- 11844178
TI  - Prenatal diagnosis of fetal tail and postabortum anatomical description.
AB  - Fetal ultrasound examination at 13 weeks of gestation demonstrated a
      homogeneously echogenic protrusion, or tail, 7 mm in length, in the sacral
      region. At 15 weeks, the ultrasound appearance was consistent with a regression
      of the tail and by 21 weeks it had completely disappeared. Severe intrauterine
      growth restriction with reduced uterine blood flow was diagnosed at 21 weeks and
      intrauterine death occurred at 24 weeks of gestation. Postmortem examination
      revealed a 4-mm caudal appendage which contained no vertebrae on radiography. The
      appendage was located under and behind the last sacral vertebra suggesting a true
      vestigial tail with a delayed process of regression.

PMID- 11844179
TI  - Early sonographic detection of a 'human tail': a case report.
AB  - We report on a newborn in whom an echogenic protrusion arising in the caudal
      region was detected at 12 weeks' gestation. Subsequent ultrasound examinations at
      weeks 15 and 22 failed to demonstrate this finding. After birth, the infant was
      found to have a pilonidal sinus. The pilonidal sinus may represent a remnant of
      the embryonic appendage ('human tail') that usually disappears by the end of the
      8th week of gestation. This case might support the theory of congenital pilonidal
      sinus origin.

PMID- 11844180
TI  - Prenatal diagnosis of a fetus with lumbar myelocystocele.
AB  - We present a case of a fetal lumbar myelocystocele, a rare congenital
      malformation, characterized by herniation of the central canal through a bony
      spina bifida. Routine ultrasound examination at 11 weeks' gestation by the
      primary obstetrician showed a suspicious cyst on the fetal back. Initially, the
      suspected diagnosis was a meningocele. After sonographic detection of newly
      developed fetal brain anomalies at 22 weeks' gestation the patient was referred
      to us. The enlarged cyst, which floated freely in the amniotic fluid, had a
      funnel-like appearance and was covered by a very thin layer of skin. With the
      help of ultrafast fetal magnetic resonance imaging the diagnosis of a fetal
      myelocystocele was made.

PMID- 11844181
TI  - In utero ultrasound detection of a large fetal sarcoma of the back.
AB  - A congenital fibrosarcoma, a very rare soft-tissue tumor of infancy, was
      suspected on prenatal ultrasound at 23 weeks' gestation. On sonography, a large
      soft tissue growth on the left side of the fetal back, measuring 53 x 65 x 22 mm,
      was observed. The diagnosis was further validated by magnetic resonance imaging.
      Delivery by Cesarian section occurred at 31 weeks of gestation, due to fetal
      distress. The baby underwent an unusual embolization of the tumor-feeding
      arteries and an operation at the age of 1 month to remove the tumor. The
      pathological and cytogenetic examinations were consistent with the diagnosis of a
      fibrosarcoma.

PMID- 11844182
TI  - Course and outcome of a pregnancy with a giant fetal cervical teratoma diagnosed
      prenatally.
AB  - We report the course and outcome of a pregnancy involving a giant fetal neck
      teratoma which was diagnosed at 23 weeks of gestation. Sonographic surveillance
      of the fetal neck revealed continuing growth of the tumor with development of
      polyhydramnios. Three-dimensional ultrasound provided additional detailed
      information on the external extent of the lesion. Color Doppler ultrasound showed
      intense arterial and venous flow with low resistance indices. Cesarean section
      under general anesthesia was planned in close cooperation with the neonatologist,
      pediatric surgeon and anesthesiologist because the size of the neck mass
      precluded vaginal delivery. Cesarean section was performed at 34 weeks of
      gestation following preterm rupture of the membranes. Orotracheal intubation was
      not successful because of compression of the airway and a tracheostomy could not
      be performed because of the risk of severe fetal hemorrhage from the tumor. The
      neonate died from respiratory insufficiency 66 min after birth.

PMID- 11844183
TI  - Re: Ductus venosus blood velocity in myeloproliferative disorders.

PMID- 11844184
TI  - Ultrasound diagnosis of a pregnancy in a Cesarean section scar.

PMID- 11844185
TI  - Diagnosis of an unusual form of iniencephaly in the first trimester of pregnancy.

PMID- 11844186
TI  - Lymphangiectasis with iniencephaly.

PMID- 11844188
TI  - The dynamic placenta: a closer look at the pathophysiology of placental
      hemodynamics in uteroplacental compromise.

PMID- 11844189
TI  - Naming veins: by morphology, physiology or sociology.

PMID- 11844190
TI  - Monitoring of fetuses with intrauterine growth restriction: a longitudinal study.
AB  - OBJECTIVE: To describe the time sequence of changes in fetal monitoring variables
      in intrauterine growth restriction and to correlate these findings with fetal
      outcome at delivery. METHODS: This was a prospective longitudinal observational
      multicenter study on 110 singleton pregnancies with growth-restricted fetuses
      after 24 weeks of gestation. Short-term variation of fetal heart rate,
      pulsatility indices of fetal arterial and venous Doppler waveforms and amniotic
      fluid index were assessed at each monitoring session. The study population was
      divided into two groups: Group 1 comprised pregnancies with severely premature
      fetuses, which were delivered < or =32 weeks and Group 2 included pregnancies
      delivered after 32 completed weeks. Logistic regression was used for modeling the
      probability for abnormality of a variable in relation to the time interval before
      delivery. Trends over time were analyzed for all variables by multilevel
      analysis. RESULTS: Ninety-three (60 in Group 1 and 33 in Group 2) fetuses had at
      least three data sets (median, 4; range, 3-27) and had the last measurements
      taken within 24 h of delivery or intrauterine death. The percentage of abnormal
      test results and the degree of abnormality were higher in Group 1 compared to
      Group 2. Amniotic fluid index and umbilical artery pulsatility index were the
      first variables to become abnormal, followed by the middle cerebral artery,
      aorta, short-term variation, ductus venosus and inferior vena cava. In Group 1,
      short-term variation and ductus venosus pulsatility index showed mirror images of
      each other in their trend over time. Perinatal mortality was significantly higher
      if both variables were abnormal compared to only one or neither being abnormal
      (13/33 (39%) vs. 4/60 (7%); P = 0.0002; Fisher's exact test). CONCLUSION: Ductus
      venosus pulsatility index and short-term variation of fetal heart rate are
      important indicators for the optimal timing of delivery before 32 weeks of
      gestation. Delivery should be considered if one of these parameters becomes
      persistently abnormal.

PMID- 11844191
TI  - The sequence of changes in Doppler and biophysical parameters as severe fetal
      growth restriction worsens.
AB  - OBJECTIVE: To test the hypothesis that hemodynamic changes depicted by Doppler
      precede deteriorating biophysical profile score in severe intrauterine growth
      restriction. METHODS: Intrauterine growth-restricted fetuses with elevated
      umbilical artery Doppler pulsatility index (PI) > 2 standard deviations above
      mean for gestational age and birth weight < 10th centile for gestational age were
      examined longitudinally. Fetal well-being was assessed serially with five
      component biophysical profile scoring (tone, movement, breathing, amniotic fluid
      volume and non-stress test) and concurrent Doppler examination of the umbilical
      artery, middle cerebral artery and ductus venosus, inferior vena cava and free
      umbilical vein. For fetuses with a final biophysical profile score < 6/10,
      progression of biophysical profile scoring, arterial PI and venous peak velocity
      indices were analyzed longitudinally. Gestational age effect was removed by
      converting indices to Z-scores (deviation from gestational age mean, in standard
      deviations). RESULTS: Forty-four of 236 intrauterine growth-restricted fetuses
      (18.6%) required delivery for abnormal biophysical profile scoring. The median
      gestational age at entry was 25 weeks and 1 day and at delivery was 29 weeks and
      6 days. The median interval between examinations was 1.5 days and the majority
      had daily testing in the week prior to delivery. Between first examination and
      delivery, significant deterioration was observed for Doppler criteria (chi
      square, P < 0.001) and biophysical parameters (Fisher's exact, P = 0.02)
      predominantly confined to the week prior to delivery/stillbirth. Doppler
      variables changed first. In 42 fetuses (95.5%), one or more vascular beds
      deteriorated, accelerating especially in the umbilical artery and ductus venosus
      at a median of 4 days before biophysical profile scoring deteriorated. Two to 3
      days before delivery, fetal breathing movement began to decline. The next day,
      amniotic fluid volume began to drop. Composite biophysical profile score dropped
      abruptly on the day of delivery, with loss of fetal movement and tone. Three
      principal patterns of Doppler deterioration were observed: (i) worsening
      umbilical artery PI, advent of brain sparing and venous deterioration (n = 32,
      72.7%); (ii) abnormal precordial venous flows, advent of brain sparing (n = 6,
      13.6%); and (iii) abnormal ductus venosus only (n = 4, 9.1%). In the majority
      (31, 70.5%), Doppler deterioration was complete 24 h before biophysical profile
      score decline. In the remainder (11, 25%), Doppler deterioration and biophysical
      profile score < 6/10 were simultaneous. CONCLUSION: In the majority of severely
      intrauterine growth-restricted fetuses, sequential deterioration of arterial and
      venous flows precedes biophysical profile score deterioration. Adding serial
      Doppler evaluation of the umbilical artery, middle cerebral artery and ductus
      venosus to intrauterine growth restriction surveillance will enhance the
      performance of the biophysical score in the detection of fetal compromise and
      therefore optimizing the timing of intervention.

PMID- 11844192
TI  - Maternal uterine artery Doppler studies at high altitude and sea level.
AB  - OBJECTIVE: To determine uterine artery impedance using Doppler in the second and
      third trimesters at sea level and at high altitude. METHODS: Uterine artery
      resistance and pulsatility indices (RI and PI, respectively) were obtained by
      Doppler velocimetry from 242 women in Cerro de Pasco (4300 m altitude) and 200
      women in Lima (sea level), all with normal singleton pregnancies between 14 and
      40 weeks of gestation. Impedance indices at high altitude and sea level were
      compared using fractional polynomial regression analysis. RESULTS: Impedance to
      uterine artery blood flow was lower at high altitude than at sea level (for PI
      ratio Lima/Cerro de Pasco = 1.06; P = 0.011). If gestation bands were compared,
      the difference was significant up to 25 weeks. CONCLUSION: At high altitude,
      pregnancy is associated with lower uteroplacental impedance than at sea level.
      This may reflect a compensatory mechanism of uteroplacental development to lower
      oxygen tension associated with altitude.

PMID- 11844193
TI  - Screening for pre-eclampsia and fetal growth restriction by uterine artery
      Doppler at 11-14 weeks of gestation.
AB  - OBJECTIVE: To examine the value of uterine artery Doppler at 11-14 weeks of
      gestation in the identification of women at risk of developing pre-eclampsia and
      fetal growth restriction. METHODS: Uterine artery Doppler was carried out at 11
      14 weeks in 3324 consecutive singleton pregnancies attending for routine care in
      three London hospitals. The right and left uterine arteries were identified using
      color flow mapping and velocity waveforms were obtained using pulsed Doppler. The
      mean pulsatility index of the two arteries was determined and the predictive
      value of a mean pulsatility index > the 95th centile in the prediction of pre
      eclampsia and/or fetal growth restriction was calculated. RESULTS: Satisfactory
      flow velocity waveforms were obtained from both uterine arteries in 3195 (96.1%)
      of the 3324 pregnancies examined and complete outcome information was obtained
      for 3045 (95.3%) of these women. The 95th centile of the uterine artery mean
      pulsatility index was 2.35 and did not change significantly with gestational age.
      The pregnancy was complicated by pre-eclampsia in 63 (2.1%) cases and by fetal
      growth restriction in 290 (9.5%) cases. The sensitivity of a mean pulsatility
      index > 2.35 for pre-eclampsia (with or without fetal growth restriction) was
      27.0% but for fetal growth restriction alone it was 11.7%. The respective
      sensitivities for these complications requiring delivery before 32 weeks of
      gestation were 60.0% and 27.8%, respectively. CONCLUSION: Uterine artery Doppler
      at 11-14 weeks of gestation identifies a high proportion of women who develop
      severe pre-eclampsia and/or fetal growth restriction.

PMID- 11844194
TI  - Uterine artery Doppler at 11-14 weeks of gestation in chromosomally abnormal
      fetuses.
AB  - OBJECTIVE: To determine whether the major chromosomal abnormalities are
      associated with impaired placentation in the first trimester of pregnancy.
      METHODS: This was a prospective study of 692 singleton pregnancies undergoing
      fetal karyotyping at 11-14 weeks of gestation. Uterine artery Doppler was carried
      out and the mean pulsatility index was calculated just before chorionic villus
      sampling. RESULTS: The fetal karyotype was normal in 613 pregnancies and abnormal
      in 79, including 39 cases of trisomy 21, 11 of trisomy 18, 11 of trisomy 13,
      eight of Turner syndrome and 10 with other defects. There were no significant
      differences in the median value of uterine artery mean PI between any of the
      individual groups. Although in the combined group of trisomy 18, trisomy 13 and
      Turner syndrome fetuses, the median pulsatility index (1.60) was significantly
      higher than in the chromosomally normal group (median pulsatility index, 1.51; P
      = 0.021), in the majority of abnormal fetuses (24 of 30) mean pulsatility index
      was below the 95th centile of the normal group (mean pulsatility index, 2.34).
      There was no significant association between uterine artery mean pulsatility
      index and fetal nuchal translucency thickness or fetal growth deficit.
      CONCLUSIONS: The high intrauterine lethality and fetal growth restriction
      associated with the major chromosomal abnormalities are unlikely to be the
      consequence of impaired placentation in the first trimester of pregnancy.

PMID- 11844195
TI  - Uterine artery Doppler and placental volume in the first trimester in the
      prediction of pregnancy complications.
AB  - OBJECTIVE: To evaluate placental volume and uterine artery Doppler in the first
      trimester in the prediction of pregnancies that subsequently develop pre
      eclampsia, pregnancy-induced hypertension, preterm placental abruption or fetal
      growth restriction. METHODS: In 380 singleton pregnancies attending our center
      for nuchal translucency screening at 11-14 weeks of gestation, Doppler assessment
      of both uterine arteries was carried out for measurement of the pulsatility index
      and the mean pulsatility index of the two vessels was calculated. In addition,
      three-dimensional ultrasound was used to obtain images for subsequent measurement
      of placental volume. The 90th centile of the uterine artery mean pulsatility
      index and the 10th centile of the placental volume for crown-rump length
      (placental quotient) were calculated. These cut-offs were used for the prediction
      of pregnancy complications. RESULTS: Complications occurred in 36 (9.5%) of the
      380 pregnancies, including 31 cases of fetal growth restriction, two of pregnancy
      induced hypertension and abruption, two of pregnancy-induced hypertension, and
      one of abruption. The uterine artery mean pulsatility index was > or =90th
      centile in 38 (10%) pregnancies and this group contained nine (25%) of those that
      developed complications. The placental quotient was < or =10th centile in 39
      (10%) pregnancies and this group contained eight (22%) of those that developed
      complications. In eight (2%) pregnancies the uterine artery mean pulsatility
      index was > or =90th centile and the placental quotient was < or =10th centile
      and this group contained six (17%) of those that developed complications.
      CONCLUSION: The combination of placental volume measurement and uterine artery
      Doppler in the first trimester may identify women at risk for subsequent
      development of pregnancy complications.

PMID- 11844196
TI  - Reproducibility and repeatability of transabdominal uterine artery Doppler
      velocimetry between 10 and 14 weeks of gestation.
AB  - OBJECTIVE: To assess the intraobserver repeatability and interobserver
      reproducibility of Doppler flow velocity measurements of the uterine arteries in
      pregnant women between 10 and 14 weeks of gestation. METHODS: In this prospective
      study, Doppler velocimetric indices (maximum peak systolic velocity, end
      diastolic velocity, peak systolic velocity/end-diastolic velocity ratio,
      pulsatility index and resistance index) were measured twice by the same trained
      observer in each uterine artery of 63 women. In 47 of these women, a second
      trained observer then repeated the measurements. In addition, both observers
      classified qualitatively the blood flow with regard to the presence or absence of
      an early diastolic notch. The coefficient of variation, intraclass correlation
      coefficients, within observer and between observers repeatability coefficient and
      Cohen's kappa coefficient were calculated. RESULTS: The best parameter in terms
      of repeatability and reproducibility in both uterine arteries was the resistance
      index with a low coefficient of variation and high intraclass correlation
      coefficient. The other parameters (pulsatility index, peak systolic velocity/end
      diastolic velocity ratio, peak systolic velocity and end-diastolic velocity)
      performed poorly with high coefficients of variation on both sides. Agreement
      between the repeated observations (inter- and intraobserver) with regard to the
      presence or absence of an early diastolic notch was good. CONCLUSION: Doppler
      velocimetry of uterine artery blood flow is technically feasible between 10 and
      14 weeks of gestation. This study demonstrates that this technique is prone to
      measurement errors. Quantitatively, the resistance index appears to be the most
      repeatable and reproducible measurement at this gestational age. Qualitative
      assessment of the waveform morphology also shows high levels of intra- and
      interobserver agreement.

PMID- 11844197
TI  - The anatomy of the umbilical, portal and hepatic venous systems in the human
      fetus at 14-19 weeks of gestation.
AB  - BACKGROUND: Ultrasound imaging of the fetal ductus venosus is becoming
      increasingly commonplace in clinical practice. The true anatomical relationships
      of the fetal umbilical and portal venous systems have not been clearly defined
      due to paucity of published data on the relevant anatomy. This has led to
      confusing terminology when describing the fetal umbilical, portal and hepatic
      circulations. The aim of the present study was to examine and document the
      anatomy of the umbilical, portal and hepatic venous systems and to propose a
      standardized nomenclature. METHODS: This was a prospective study on 11 fetuses
      obtained from medical termination of pregnancies between 14 and 19 weeks of
      gestation. The liver was microdissected to expose the branching pattern and
      anatomical relations of the umbilical, portal and hepatic venous systems.
      RESULTS: A wide L-shaped venous confluence at the terminal end of the umbilical
      vein, termed the portal sinus, was identified. The portal sinus was connected to
      the right and left hepatic lobes, by the right and left intrahepatic portal
      veins, respectively. The extrahepatic portal vein drained into the portal sinus
      just before the origin of the right intrahepatic portal vein. The ductus venosus,
      a branchless straight vessel, originated from the portal sinus and ascended
      steeply in the direction of the diaphragm. Numerous small vessels draining the
      liver converged into three main hepatic veins, which open into the
      subdiaphragmatic vestibulum. CONCLUSION: Based on detailed sequential anatomical
      dissection and clear illustrations, the present study documents the anatomy of
      the umbilical, portal and hepatic venous systems. Taking into account the
      embryological origin of the vessels, a new anatomically appropriate and
      simplified nomenclature of these venous systems is proposed. In clinical
      practice, the consistent use of the suggested terminology would allow collection
      of comparable data between units and enable operators to be confident of which
      vessels they are sampling by Doppler ultrasound.

PMID- 11844199
TI  - Incidence of major structural cardiac defects associated with increased nuchal
      translucency but normal karyotype.
AB  - OBJECTIVE: To examine the association between increased nuchal translucency
      thickness and major cardiac defects in chromosomally normal fetuses. SETTING:
      Tertiary referral unit for fetal medicine and fetal cardiology. METHODS: During a
      4-year period (January 1997 to January 2001), detailed echocardiography was
      performed in 1319 chromosomally normal fetuses with increased nuchal translucency
      thickness at 10-14 weeks of gestation. The incidence of major cardiac defects was
      examined in relation to the fetal NT at the 10-14-week scan. RESULTS: Major
      cardiac defects were diagnosed in 60 (4.5%) of the 1319 fetuses. In fetuses with
      a nuchal translucency thickness in the range of 2.5-3.4 mm, the incidence of
      major cardiac defects was 2.5% (18/722; 95% confidence interval, 1.5-3.9) and in
      those with a nuchal translucency thickness > or =3.5 mm, it was 7% (42/597; 95%
      confidence interval, 5.1-9.4). CONCLUSION: Specialist echocardiography is
      indicated in all fetuses with increased nuchal translucency thickness because, in
      such fetuses, the incidence of major cardiac defects is substantially higher than
      in pregnancies with maternal diabetes, family history and exposure to drugs,
      where fetal echocardiography is widely considered to be necessary.

PMID- 11844198
TI  - Absence of the ductus venosus: report of 10 new cases and review of the
      literature.
AB  - OBJECTIVE: To assess the clinical significance of the absence of the ductus
      venosus. DESIGN: A retrospective study with a review of the literature. METHODS:
      The archives of our ultrasound laboratory and the English literature were
      searched for cases with a prenatal diagnosis of absence of the fetal ductus
      venosus. RESULTS: Between 1985 and 2000, 10 fetuses were diagnosed in our center
      as having absence of the ductus venosus. The review of the literature revealed 23
      cases. Three main patterns of abnormal venous circulation were documented: (1)
      umbilical vein bypassing the liver and connecting directly to the right atrium
      (46%); (2) umbilical vein bypassing the liver and connecting to the inferior vena
      cava mostly through one of the iliac veins (25%); (3) umbilical vein connecting
      to the portal circulation without giving rise to the ductus venosus (21%). Major
      anomalies, including chromosomal aberrations, were found in 8/33 (24%) cases.
      Hydrops developed in 11/33 (33%) cases. Twenty fetuses with isolated absence of
      the ductus venosus were delivered, and 5 (20%) died. The portal vein was found to
      be absent in half of the infants examined after birth. CONCLUSIONS: Our results
      and the review of literature suggest that absence of the ductus venosus is
      associated with a high incidence of fetal anomalies and adverse outcomes,
      including associated malformations, chromosomal aberrations, in utero heart
      failure and absence of the portal vein. Heart failure and absence of the portal
      vein seem particularly frequent when absence of the ductus venosus is associated
      with a connection of the umbilical vein to either the inferior vena cava or the
      right atrium.

PMID- 11844200
TI  - Diagnosis and management of fetal cardiac anomalies: 10 years of experience at a
      single institution.
AB  - OBJECTIVE: To assess the diagnostic accuracy of fetal echocardiography and the
      outcome of cardiac malformations diagnosed in utero. DESIGN: A retrospective
      study. METHODS: The archives of our ultrasound laboratory were searched for fetal
      cardiac abnormalities in the period 1991-2001. RESULTS: Diagnosis of a fetal
      cardiac anomaly was made in 339 pregnancies at a mean gestational age of 26.2
      weeks. Pathology or a detailed postnatal follow-up was available in 260 cases,
      and the prenatal diagnosis was accurate in 236 cases (91%). Discrepancies
      included nine false positive diagnoses (six ventricular septal defects and three
      coarctation of the aorta) and 15 cases in which a cardiac anomaly different from
      the one suspected in utero was documented. Of the 142 fetuses with isolated
      cardiac malformations (no extracardiac anomalies, normal chromosomes) that were
      delivered in our center, 114 were alive (80.2%) at a mean follow-up of 38 months
      (range, 1-120 months). In this group of patients, conotruncal anomalies and
      univentricular lesions were the most frequent types of anomaly, and had a
      survival rate of 87% and 57%, respectively. Hypoplastic left heart was the most
      frequent isolated congenital heart defect in infants that were delivered (19
      cases) and it was associated with a survival rate of 37%. CONCLUSION: In expert
      hands, fetal echocardiography is highly accurate. The long-term prognosis of
      cardiac lesions diagnosed in utero is similar to that reported in series of
      infants diagnosed after birth. The only exception is hypoplastic left heart in
      which the survival rate is much lower than expected from postnatal studies.

PMID- 11844201
TI  - Right and left ventricular long-axis function in the fetus using angular M-mode.
AB  - OBJECTIVE: Long-axis function is determined by the longitudinally oriented
      myocardial fibers. Postnatally, conventional M-mode is used to assess tricuspid
      and mitral valve ring movements in relation to the cardiac apex. During fetal
      life, this is precluded by variable fetal position. We assessed the feasibility
      of determining right and left ventricular long-axis function in the fetus.
      METHODS: A prospective, pilot study. The four-chamber view obtained during
      routine fetal echocardiography was recorded in a cineloop to which B-mode guided
      M-mode echocardiography was applied using angular M-mode. This allowed
      retrospective and correct placement of the cursor line from cardiac apex to
      tricuspid or mitral valve rings. M-mode tracings of the valve ring movements in
      relation to the apex were derived from the originally stored loop. Data from 18
      fetuses (17-29 weeks of gestation) were available for analysis. Total excursion
      of the valve rings was measured offline. A second cursor line was simultaneously
      placed in the left ventricular outflow tract during color flow mapping for timing
      purposes (n = 6). RESULTS: Right and left ventricular long-axis recordings were
      obtained in 18 and 14 cases, respectively. Total right ventricular excursion was
      5.2 mm (SD, 0.9 mm) (range, 3.9-7.2 mm). Total left ventricular free wall
      excursion was 4.5 mm (SD, 1.1 mm) (range, 3.0-6.8 mm). For paired data, the mean
      of differences (right ventricle-left ventricle) was 0.8 mm (95% confidence
      interval 0.5-1.2). The valve rings moved towards the apex during systole
      (shortening) and away from it during diastole (lengthening). Peak downward
      movement coincided with cessation of aortic flow and diastolic lengthening with
      flow through the atrioventricular valves. CONCLUSION: Long-axis function in the
      fetus is feasible if M-mode angle correction is used. There was no clinically
      significant difference between tricuspid and mitral valve excursions. The pattern
      of atrioventricular valve movement is coordinate and similar to that of adults.
      Long-axis function offers a new avenue to study systolic and diastolic function
      in the fetus.

PMID- 11844202
TI  - Preinduction sonographic measurement of cervical length in the prediction of
      successful induction of labor.
AB  - BACKGROUND: Induction of labor is carried out in approximately 20% of
      pregnancies. However, approximately 20% of women having induction of labor end up
      having a Cesarean delivery. The traditional method of predicting whether an
      induced labor will result in successful vaginal delivery is based on the
      preinduction "favorability" of the cervix as assessed by the Bishop score.
      However, this assessment is subjective and several studies have shown a poor
      predictive value for the outcome of induction. OBJECTIVES: To examine the
      relationship between preinduction sonographically measured cervical length and
      the Bishop score and to compare the two measurements in the prediction of
      successful vaginal delivery within 24 h of induction. METHODS: In this
      multicenter study, preinduction cervical assessment was undertaken in 240 women
      with singleton pregnancies at 37-42 weeks of gestation. The Bishop score was
      assessed by digital examination and the cervical length was measured by
      transvaginal sonography. RESULTS: Multiple regression analysis demonstrated that
      cervical length, Bishop score and parity provided independent contribution in the
      prediction of the likelihood of delivering vaginally within 24 h. Further
      examination of the different components of the Bishop score showed that only
      cervical length provided a significant contribution in the prediction of the
      likelihood of vaginal delivery within 24 h. In the receiver operating
      characteristic curves, the best cut-off point for the prediction of successful
      induction was 28 mm for cervical length and 3 for the Bishop score. However,
      cervical length appears to be a better predictor than the Bishop score, with a
      sensitivity of 0.87 and a specificity of 0.71 compared to 0.58 and 0.77,
      respectively. Similarly, the Kaplan-Meier survival curves indicate that better
      discriminatory results in the prediction of vaginal delivery within 24 h are
      achieved using cervical length rather than the Bishop score. CONCLUSION:
      Transvaginal sonographic measurement of cervical length provides a useful
      prediction of the likelihood of vaginal delivery within 24 h of induction.

PMID- 11844204
TI  - Relationship between nuchal translucency at 11-14 weeks and nuchal fold at 20-24
      weeks of gestation.
AB  - OBJECTIVES: To examine the relationship between the measurement of nuchal
      translucency in the first trimester and nuchal fold in the second trimester in
      normal pregnancy. METHODS: This was a prospective study of 592 singleton
      pregnancies. Fetal nuchal translucency was measured at 11-14 weeks of gestation
      and nuchal fold at 20-24 weeks of gestation. Linear regression models were used
      to assess the relationship between nuchal translucency and nuchal fold after
      adjustment for gestational age. RESULTS: There was no significant association
      between nuchal translucency and nuchal fold thickness. CONCLUSION: It is possible
      that measurement of nuchal translucency and nuchal fold may provide an
      independent contribution in screening for trisomy 21.

PMID- 11844203
TI  - Randomized study of vaginal misoprostol (PGE(1)) and dinoprostone gel (PGE(2))
      for induction of labor at term.
AB  - OBJECTIVES: To investigate the efficacy and safety of misoprostol in the
      induction of labor at term by comparing this agent with the commonly used
      dinoprostone gel. PATIENTS AND METHODS: A randomized clinical trial of vaginal
      misoprostol, 50 microg 6-hourly, and dinoprostone gel, 1-2 mg 6-hourly, in 435
      women undergoing induction of labor at term. The women, 210 in the misoprostol
      group and 225 in the dinoprostone group, were compared to determine whether there
      was a significant difference in achieving vaginal delivery within 24 h, the
      incidence of hyperstimulation syndrome, Cesarean section rate and adverse
      neonatal outcome. They were also offered the option of preinduction sonographic
      cervical assessment. RESULTS: Misoprostol, compared to dinoprostone gel, was
      associated with a significantly shorter median induction-to-delivery interval
      (14.6 h vs. 19.0 h; P = 0.0014), a higher incidence of vaginal delivery within 24
      h of induction (65.7% vs. 54.2%; P = 0.019) and a reduced need for oxytocin
      augmentation during labor (20.5% vs. 29.8%; P = 0.034). The groups did not differ
      significantly in the rates of Cesarean section (18.1% vs. 19.1%; P = 0.88) and
      hyperstimulation syndrome (2.4% vs. 0.9%; P = 0.27). None of the cases of
      hyperstimulation required treatment with tocolysis. All nine cases of excessive
      uterine contractility occurred after the first dose of the drug. There were no
      significant differences in maternal and neonatal morbidity between the two
      groups. There was a significant association between preinduction cervical length
      and the induction-to-delivery interval in both those receiving misoprostol and
      those treated with dinoprostone. CONCLUSIONS: The use of misoprostol is
      associated with a shorter duration of labor and a higher rate of vaginal delivery
      within 24 h from induction without an increase in maternal and neonatal
      morbidity. Transvaginal sonographic measurement of cervical length is useful in
      the prediction of the likelihood of vaginal delivery within 24 h of induction and
      of the induction-to-delivery interval and may be useful in the stratification of
      patients participating in randomized studies that examine the effectiveness of
      inducing agents.

PMID- 11844205
TI  - The effects of maternal and fetal parameters on the quality of nuchal
      translucency measurement.
AB  - OBJECTIVE: To evaluate the influence of maternal and fetal parameters on the
      quality of fetal nuchal translucency measurement. DESIGN: This was a prospective
      study in 227 consecutive pregnant women undergoing nuchal translucency screening
      by transabdominal sonography. The same well-qualified sonographer performed all
      the scans and in each case the best-quality image was selected and scored
      according to an image scoring system (total maximum score, 9). The quality of the
      image was examined in relation to maternal age, weight, abdominal wall thickness,
      amniotic sac diameter, posterior uterine wall depth (distance between abdominal
      wall surface and posterior uterine wall surface), placental location, fetal crown
      rump length and nuchal translucency thickness. Correlation coefficients were
      calculated and stepwise linear regression was used to adjust for confounders and
      to define the predictors for image score. RESULTS: The only two parameters that
      provided a significant independent contribution to the prediction of the image
      score were posterior uterine wall depth and fetal crown-rump length.
      Intravariable analysis of these two parameters demonstrated that the cut-off
      associated with a significant change in the image quality was 80 mm for posterior
      uterine wall depth (score difference, 1.06; P < 0.001) and 70 mm for crown-rump
      length (score difference, 0.77; P = 0.001). In the group of women with two values
      above these cut-off points, an average score decrease of 1.90 (P < 0.001) was
      observed. CONCLUSIONS: The quality of fetal nuchal translucency measurement is
      poorer when the fetal crown-rump length is > 70 mm and the posterior uterine wall
      depth is > 80 mm.

PMID- 11844206
TI  - Quality assessment in prospective nuchal translucency screening for Down
      syndrome.
AB  - OBJECTIVES: To develop and apply a quality control system in a Down syndrome
      screening study using nuchal translucency as an interventional marker. METHODS:
      In a prospective Down syndrome screening study fetal nuchal translucency
      thickness was measured in 9236 of the 10 045 examined pregnancies. For quality
      assessment two models were introduced: firstly, image-scoring evaluation of the
      nuchal translucency thickness measurements and secondly, establishment of the
      distributions of nuchal translucency multiples of the median over time and the
      influence of intervention. RESULTS: The observer variability in the image-scoring
      evaluation was high with a kappa value of 0.48 in the overall validation. A
      revised model showed better interobserver agreement with a kappa value of 0.58;
      however, comparing the individual criteria the differences were still
      unsatisfactory, i.e. we found highly significant differences in the criteria
      "position of the fetus" (P = 0.0026) and "magnification of the image" (P =
      0.0001). Regarding the distributions of the nuchal translucency multiples of the
      median, the median stabilized after a short learning phase representing the
      practical part of the sonographer's certification to nuchal translucency
      screening. In groups of medians of 50 nuchal translucency multiples of the median
      the intergroup standard deviation decreased from 0.100-0.060 after the learning
      phase to 0.046 after intervention. CONCLUSIONS: When well-trained certified
      examiners perform nuchal translucency screening, continuous evaluation of the
      distribution of the nuchal translucency multiples of the median seems to be a
      good method to assess the quality for a center and may also be used to identify
      individual examiners deviating from the mean performance. The image-scoring
      methods we introduced cannot be recommended for quality control in a nuchal
      translucency screening program.

PMID- 11844207
TI  - Screening for trisomy 21 by fetal nuchal translucency and maternal age: a
      multicenter project in Germany, Austria and Switzerland.
AB  - OBJECTIVE: To examine the effectiveness of screening for trisomy 21 by a
      combination of maternal age and fetal nuchal translucency thickness at 10-14
      weeks of gestation in Germany, Austria and Switzerland. METHODS: This was a
      multicenter study of screening for trisomy 21 by a combination of maternal age
      and fetal nuchal translucency thickness at 10-14 weeks of gestation. All the
      sonographers involved in the study had received The Fetal Medicine Foundation
      Certificate of Competence in the 10-14-week scan. Fetal nuchal translucency
      thickness and crown-rump length were measured in 23 805 singleton pregnancies
      with live fetuses. In each case the risk for trisomy 21 was estimated on the
      basis of maternal age and fetal nuchal translucency thickness for crown-rump
      length with the use of The Fetal Medicine Foundation's software. The distribution
      of estimated risk was determined and the sensitivity and false-positive rate for
      a risk cut-off of 1 in 300 was calculated. RESULTS: Fetal nuchal translucency
      thickness was successfully measured in all 23 805 pregnancies and outcome was
      available in 21 959. The median maternal age was 33 (range 15-49) years and in
      7935 (36.1%) the age was 35 years or greater. The median gestation at screening
      was 12 (10-14) weeks and the median fetal crown-rump length was 61 (range 38-84)
      mm. The estimated risk for trisomy 21 based on maternal age and fetal nuchal
      translucency thickness for crown-rump length was 1 in 300 or greater in 13.0%
      (2800 of 21 475) normal pregnancies, in 87.6% (184 of 210) of those with trisomy
      21 and in 87.2% (239 of 274) with other chromosomal defects. CONCLUSIONS: In
      Germany, Austria and Switzerland the results of screening for chromosomal defects
      by measurement of fetal nuchal translucency thickness, in centers with
      appropriately qualified sonographers and using The Fetal Medicine Foundation's
      software, are similar to those reported in the UK using the same methodology.

PMID- 11844208
TI  - Fetal nuchal translucency screening in 12495 pregnancies in Sardinia.
AB  - OBJECTIVE: To examine the distribution of fetal nuchal translucency thickness in
      normal and chromosomally abnormal fetuses in Sardinia and to determine the
      effectiveness of screening by a combination of fetal nuchal translucency and
      maternal age. METHODS: Fetal nuchal translucency thickness and crown-rump length
      were measured at 10-14 weeks of gestation in 12 495 pregnancies. A reference
      range of fetal nuchal translucency thickness for crown-rump length was determined
      from the 10 001 singleton pregnancies with known normal pregnancy outcome. The
      median nuchal translucency thickness for crown-rump length was determined by
      regression analysis of the calculated median values of nuchal translucency
      thickness for each 0.1 mm interval in crown-rump length. The proportions of
      unaffected fetuses and those with trisomy 21 or other chromosomal defects with
      nuchal translucency thickness > 1.5 and 2.0 multiples of the regressed normal
      median for crown-rump length were calculated. The distribution of estimated risks
      based on maternal age and fetal nuchal translucency thickness according to The
      Fetal Medicine Foundation software were also determined and the sensitivity and
      false-positive rates were calculated. RESULTS: In the 10 001 normal pregnancies,
      the median fetal nuchal translucency thickness increased with crown-rump length
      (median nuchal translucency thickness = 0.3496 + 0.018 x crown-rump length) (r2 =
      0.4411). In the singleton pregnancies, there were 64 fetuses with trisomy 21 and
      46 with other chromosomal defects. The fetal nuchal translucency thickness was >
      1.5 multiples of the median in 510 (5%) of the normal fetuses, in 52 (81%) of the
      trisomy 21 fetuses and in 33 (72%) of those with other chromosomal defects. The
      respective values for nuchal translucency thickness > 2.0 multiples of the median
      were 195 (2%), 41 (64%) and 32 (70%). In 184 multiple pregnancies, there were
      four fetuses with chromosomal abnormalities and in three of these the nuchal
      translucency thickness was > 1.5 multiples of the median. Screening by a
      combination of maternal age and fetal nuchal translucency thickness with a risk
      cut-off of 1 in 300 identified 90% of trisomy 21 pregnancies and 85% of all other
      chromosomal defects for a false-positive rate of 9%. CONCLUSION: Screening for
      chromosomal defects by measurement of nuchal translucency thickness identifies
      80% of fetuses with trisomy 21 for a false-positive rate of 5%. In our population
      with a median maternal age of 33 years, screening by a combination of maternal
      age and fetal nuchal translucency thickness with a risk cut-off of 1 in 300
      identified 90% of trisomy 21 pregnancies for a false-positive rate of 9%.

PMID- 11844209
TI  - First-trimester screening for chromosomal abnormalities by fetal nuchal
      translucency in a Brazilian population.
AB  - OBJECTIVES: To examine the detection rate of chromosomal abnormalities using
      nuchal translucency (NT) thickness in a Brazilian population. METHODS: This was a
      prospective study of 2996 singleton pregnancies with a live fetus at 10-14 weeks
      of gestation attending for routine antenatal care in a teaching hospital in
      Brazil. Fetal crown-rump length (CRL) and NT thickness were measured and the
      risks for trisomy 21 were calculated by a combination of maternal age and fetal
      NT with the use of software provided by The Fetal Medicine Foundation.
      Sensitivity and positive predictive values for different risk cut-offs were
      calculated. RESULTS: Chromosomal defects were diagnosed in 22 cases, including 10
      cases of trisomy 21. The estimated risk based on maternal age and fetal NT was 1
      in 300 or greater in 222 (7.4%) cases and these included nine of 10 (90.0%)
      pregnancies with trisomy 21 and nine of 12 (75.0%) pregnancies with other
      chromosomal defects. The NT was above the 95th centile in 5.8% of cases and this
      group included 70% of the trisomy 21 cases. CONCLUSION: A combination of maternal
      age and fetal NT provides an effective method of screening for chromosomal
      defects. The performance of the test in a Brazilian population is similar to that
      in Britain.

PMID- 11844210
TI  - Doppler ultrasound measurements in the central circulation of anesthetized fetal
      sheep during obstruction of umbilical-placental blood flow.
AB  - OBJECTIVE: To establish by Doppler ultrasound the effects of acute blockage of
      umbilical cord vessels on the fetal central circulation. DESIGN: Experimental
      study in anesthetized pregnant sheep. METHODS: In 11 anesthetized pregnant sheep
      (0.66 of gestation), Doppler velocity profiles and/or venous flow rates were
      recorded in the ductus venosus, the fetal aorta, the umbilical arteries and the
      umbilical vein. This involved three phases. In Phase 1, the abdominal wall was
      closed (n = 9); Phase 2 was during fetoscopy after laparotomy (n = 8); Phase 3
      was after coagulation of one of the umbilical arteries (n = 10). As an additional
      intervention in six fetuses, the umbilical cord was clamped for 5-15 s while
      blood flow velocity changes in the ductus venosus were observed. RESULTS: There
      were no significant differences between Doppler recordings in Phases 1 and 2.
      During Phase 3, the pulsatility index of the aorta and of the coagulated
      umbilical artery increased significantly. The umbilical vein blood flow rate was
      significantly reduced from a median of 408 (range, 243-575) mL/min/kg in Phase 1
      to a median of 173 (range, 107-426) mL/min/kg in Phase 3, but the blood flow rate
      in the ductus venosus (median, 94; range, 56-148 mL/min/kg vs. median, 92; range,
      33-237 mL/min/kg) remained unchanged. The ductus venosus/umbilical vein ratio
      increased from a median of 0.22 (range, 0.13-0.41) to 0.56 (range, 0.17-0.97) (P
      < 0.05). Compression of the cord (5-15 s) immediately reduced the time averaged
      maximum velocity in the ductus venosus from a mean of 51 (standard deviation, 11)
      cm/s to 20 (standard deviation, 6) cm/s (P < 0.001) without significant changes
      of the velocity profile. However, the pulsatility index increased from a mean of
      0.55 (standard deviation, 0.19) to 1.89 (standard deviation, 0.73) (P < 0.001).
      CONCLUSION: Central venous flows in anesthetized fetal sheep are unaffected by
      laparotomy and hysterotomy. Obliteration of one umbilical artery increases the
      ductus venosus/umbilical vein volume flow (mL/min/kg) ratio. Compression of the
      umbilical cord shifts down blood flow velocity profiles in the ductus venosus,
      and the pulsatility index thus increases.

PMID- 11844211
TI  - The diagnostic implications of routine ultrasound examination in histologically
      confirmed early molar pregnancies.
AB  - OBJECTIVE: Early ultrasound examination is being used increasingly in the
      diagnosis of molar pregnancy. The aim of this study was to examine the diagnostic
      implications of routine ultrasound examination for histologically confirmed molar
      pregnancies. METHODS: This was a retrospective review of sonographic and
      histological findings in a series of consecutive cases referred to the National
      Trophoblastic Disease Surveillance Centre with suspected molar pregnancies. In
      194 cases referred to the center over a 6-month period in whom results of a
      preceding ultrasound examination were documented, review of ultrasound findings
      and final histological diagnosis was carried out. RESULTS: There were 155 cases
      with a reviewed histological diagnosis of complete or partial hydatidiform mole.
      In 131 (67%) cases, the sonographic diagnosis was that of a missed
      miscarriage/anembryonic pregnancy with no documented suspicion of molar
      pregnancy, referral being on the basis of histological examination of products of
      conception. In 63 cases, ultrasound examination suggested molar pregnancy; in 53
      (84%) of these, the diagnosis of molar pregnancy was correct. Overall, 37 of 64
      (58%) complete moles had sonographic evidence of molar pregnancy compared to 16
      of 91 (17%) partial moles. Of 155 histologically confirmed complete or partial
      hydatidiform moles, only 53 (34%) were suspected as molar sonographically.
      CONCLUSION: The majority of cases of molar pregnancy now present as missed
      miscarriage/anembryonic pregnancy sonographically, highlighting the importance of
      histological examination to diagnose gestational trophoblastic disease.

PMID- 11844212
TI  - Controlled fetal blood-letting of the recipient twin as a new method for the
      treatment of severe twin-twin transfusion syndrome: preliminary results.
AB  - OBJECTIVE: To investigate the feasibility of withdrawal of blood from the
      recipient twin as a new method for the treatment of severe twin-twin transfusion
      syndrome. METHODS: Seven consecutive monozygotic monochorionic twin pregnancies
      affected by severe twin-twin transfusion syndrome were treated. Fetal blood was
      withdrawn from the recipient twin using cordocentesis. The volume of blood to be
      removed was determined using the formula for intrauterine blood transfusion of
      anemic fetuses. Fetal outcome was evaluated in relation to changes in the
      amniotic fluid and in growth curves (comparing the differences between the
      centiles of the estimated fetal weight before the procedure and the centiles of
      weight at birth), fetal mortality, gestational age at delivery, neonatal weight
      and neurological damage. RESULTS: Overall, seven of the 14 (50%) fetuses
      survived; at least one fetus survived in five (71%) pregnancies, both fetuses
      survived in two (29%) pregnancies, while in two (29%) pregnancies there were no
      survivors. No maternal complications were observed. At follow-up, one (14%) baby
      had minor neurological damage. CONCLUSIONS: Withdrawal of blood from the
      recipient twin in the treatment of severe twin-twin transfusion syndrome was
      associated with survival similar to that of the alternative techniques of serial
      amniodrainage and fetoscopic laser surgery, with some possible advantages such as
      reduced neurological damage compared with serial amniodrainage. It is also less
      invasive compared with fetoscopic laser surgery.

PMID- 11844213
TI  - Acquired right heart outflow tract anomaly without systemic hypertension in
      recipient twins in twin-twin transfusion syndrome.
AB  - Significant hemodynamic changes are commonly observed in both fetuses in twin
      twin transfusion syndrome. In the recipient twin there is cardiac dysfunction
      with hypertrophy of both ventricles and overall enlargement of the heart. We
      describe five cases of recipient twins in twin-twin transfusion syndrome with
      right ventricle hypertrophy, pulmonary stenosis and tricuspid regurgitation
      acquired in utero. These symptoms developed with no signs of systemic
      hypertension. Three of the five recipient twins survived and were developing
      normally at 3-30 months of age. Postnatal outcome is likely to have improved as a
      result of prenatal diagnosis of right ventricle outflow tract obstruction and
      timed delivery. These acquired anomalies of the right heart might be related to
      the particular hemodynamic conditions of the recipient twin. A global heart
      dilatation is logically expected, but this hypertrophy without dilatation is
      probably related to the shared plasma of fetuses with opposite hemodynamic
      conditions. This is what we consider as the hemodynamic-hormonal paradox. These
      acquired anomalies, though severe, are accessible to neonatal treatment if
      treated early.

PMID- 11844214
TI  - Spontaneous resolution of amniotic bands.
AB  - The amniotic band syndrome comprises a group of sporadic congenital anomalies
      characterized by amputations, constriction bands, pseudosyndactylism and multiple
      craniofacial, visceral and body wall defects. It occurs in approximately 1 in
      1200 to 1 in 15 000 live births. Some of the cases present with congenital
      anomalies that are incompatible with life, but a selected group shows isolated
      limb constrictions. Repeated sonographic examinations afforded us the opportunity
      of observing the in utero process of limb strangulation and subsequent
      spontaneous lysis of an amniotic band attached to a fetal elbow. Surgical fetal
      therapy with lysis of the constriction ring in utero is an option, but
      intervention is probably not always warranted. Spontaneous resolution does occur.

PMID- 11844215
TI  - A movable gestational sac in association with a myometrial defect.
AB  - An ultrasound examination in a woman at 9 weeks' gestation demonstrated a
      gestational sac with a live fetus in the left uterine horn which was surrounded
      by an extremely thin outer lining. An interstitial pregnancy was suspected and
      laparoscopy was performed. During laparoscopy the purple bulge in the left horn
      gradually reduced in size and eventually disappeared following the external
      pressure by the tip of the forceps. We believe this pressure caused contraction
      of the superficial myometrial fibers resulting in a shift in the location of the
      gestational sac to the central area of the uterus. The pregnancy continued and on
      Cesarean section at 34 weeks' gestation, a membranous protrusion of the uterine
      wall in the left horn was noticed. A myometrial defect caused by an intrauterine
      intervention in the patient's previous pregnancy was suspected to be the cause of
      this "movable gestational sac" phenomenon.

PMID- 11844216
TI  - Prenatal diagnosis of a rare variant of hypospadias and review of the literature.
AB  - We present a case of a variant of hypospadias, diagnosed prenatally at 21 weeks'
      gestation, in which the penis and scrotum appeared normal but there was a cyst
      like lesion and a urethrocutaneous fistula on the ventral side of the penis.
      Detailed sonographic examination and karyotyping confirmed this was an isolated
      lesion and helped the parents to decide on continuation of the pregnancy.

PMID- 11844217
TI  - Intra-amniotic ultrasound.

PMID- 11844218
TI  - Two- and three-dimensional sonography of a monochorionic triplet gestation.

PMID- 11844219
TI  - The mast cell in wound healing.
AB  - This review describes the role of the mast cell in the pathobiology of skin
      healing. After illustrating its main morphofunctional characteristics, with
      special reference to the dog and cat, we consider the involvement of the mast
      cell in the various phases of skin repair. With the aid of a wide array of newly
      formed or preformed mediators released by degranulation, the activated mast cell
      controls the key events of the healing phases: triggering and modulation of the
      inflammatory stage, proliferation of connective cellular elements and final
      remodelling of the newly formed connective tissue matrix. The importance of the
      mast cell in regulating healing processes is also demonstrated by the fact that a
      surplus or deficit of degranulated biological mediators causes impaired repair,
      with the formation of exuberant granulation tissue (e.g. keloids and hypertrophic
      scars), delayed closure (dehiscence) and chronicity of the inflammatory stage.

PMID- 11844220
TI  - Evaluation of an enzyme-linked immunosorbent assay (ELISA) for the serological
      diagnosis of sarcoptic mange in dogs.
AB  - Canine scabies is a challenging disease to diagnose because sarcoptic mites are
      hard to find on skin scrapings. The purpose of this study was to evaluate a
      serologic enzyme-linked immunosorbent assay (ELISA) as an aid in the diagnosis of
      canine scabies. In addition, serum samples were obtained post treatment to
      determine the duration and persistence of circulating scabies antibodies after
      resolution of natural infection. Nineteen dogs diagnosed with sarcoptic mange and
      38 control dogs were tested. Sixteen scabies-infested dogs showed positive
      pretreatment ELISA results (84.2% sensitivity). Thirty-four control dogs showed
      negative ELISA results (89.5% specificity). In the 11 scabies dogs from which
      multiple post treatment serum samples were obtained, detectable antibodies were
      not present 1 month after treatment in four cases, but were present for 1-4.5
      months post treatment in seven dogs. Our results suggest that this scabies ELISA
      test is useful in the diagnosis of canine scabies.

PMID- 11844221
TI  - Assessment of proliferative activity of canine dermal mast cells by
      bromodeoxyuridine and proliferating cell nuclear antigen labelling.
AB  - Cutaneous mast cells from skin biopsies of three healthy dogs and three dogs with
      atopic dermatitis were assessed for their proliferative potential using
      bromodeoxyuridine and proliferating cell nuclear antigen labelling. Mast cells
      isolated from the skin of two healthy dogs were also studied using
      bromodeoxyuridine labelling. Mast cells in skin biopsy specimens and mast cells
      isolated from the skin of healthy dogs did not incorporate bromodeoxyuridine. Two
      mast cells expressing proliferating cell nuclear antigen were seen around two
      superficial vessels in the dermis of one atopic dog. Epidermal cells, glandular
      epithelial cells, fibroblasts and endothelial cells incorporated
      bromodeoxyuridine and showed positive staining for proliferating cell nuclear
      antigen. These results suggest that canine mature mast cells do not proliferate
      in the dermis.

PMID- 11844222
TI  - Serum antibodies to Malassezia yeasts in canine atopic dermatitis.
AB  - Significant numbers of humans with atopic dermatitis develop Malassezia-specific
      IgE. Immediate skin-test reactivity to Malassezia has been demonstrated in atopic
      dogs. The aim of this study was to compare the serum IgG and IgE response to
      Malassezia in atopic dogs with and without clinical evidence of Malassezia
      dermatitis and/or otitis, nonatopic dogs with clinical evidence of Malassezia
      dermatitis and/or otitis and healthy dogs. Cytology was used to diagnose
      clinically significant Malassezia dermatitis and otitis. Contact plate cultures
      confirmed the validity of this technique. Reproducible enzyme-linked
      immunosorbent assays for Malassezia-specific IgG and IgE in canine serum were
      established. Atopic dogs had significantly higher serum IgG and IgE levels than
      either healthy dogs or nonatopic dogs with clinical evidence of Malassezia
      dermatitis and/or otitis. There was no significant difference in IgG and IgE
      levels between atopic dogs with and without clinical evidence of Malassezia
      dermatitis and/or otitis. The implications of these findings in the pathogenesis
      and management of canine atopic dermatitis are discussed.

PMID- 11844223
TI  - Histopathological study of feline eosinophilic dermatoses.
AB  - A retrospective study was conducted on skin specimens from 24 cats with
      eosinophilic granuloma complex. The specimens were stained with haematoxylin and
      eosin and Gallego's trichrome stain. In all specimens, flame figures and/or large
      foci of so-called "collagen degeneration" were detected and histopathological
      features were not predictive of the clinical picture. Use of the term
      eosinophilic dermatosis was advocated in diagnostic dermatopathology. On
      trichrome-stained sections, normally stained collagen fibres were identified in
      the middle of both flame figures and large foci of "collagen degeneration" and
      the debris surrounding collagen bundles showed the same tinctorial properties as
      eosinophil granules. Eosinophil degranulation around collagen bundles seemed to
      represent the major pathogenetic event in these lesions, analogous with human
      flame figures. The term flame figures might therefore be more accurately used to
      designate those foci of eosinophilic to partly basophilic debris commonly
      referred to as "collagen degeneration".

PMID- 11844224
TI  - Skin mast cell histamine release following stem cell factor and high-affinity
      immunoglobulin E receptor cross-linking in dogs with atopic dermatitis.
AB  - Stem cell factor (SCF) influences mast cell activation and inflammatory mediator
      release, and is elevated in tissues undergoing allergic inflammation. Wheal
      formation in response to the injection of SCF or anti-immunoglobulin (Ig)E
      antibody injection was compared between normal (n = 10) and nonlesional atopic (n
      = 10) canine skin. In situ SCF secretion was compared between lesional and
      nonlesional skin using immunohistochemistry. Histamine release by skin cell
      suspensions after stimulation with SCF, concanavalin A (ConA) or rabbit
      anticanine IgE antibodies was compared between normal and atopic dogs. All dogs
      exhibited strong responses to intradermal SCF injection at 10 and 50 ng mL(-1).
      Atopic dogs had significantly (P = 0.002) larger wheal responses to anti-IgE than
      normal dogs; but there was no difference in numbers of skin mast cells bearing
      IgE as detected by immunohistochemistry. Only atopic dogs exhibited interstitial
      deposition of SCF in both lesional and nonlesional skin specimens. Median
      histamine release stimulated by SCF in the absence of IgE from lesional skin
      cells was higher in atopic than normal dogs (P = 0.04). These experiments suggest
      that dermal SCF secretion could potentiate histamine release following IgE
      receptor cross-linking and thus, could be one of the explanations for the
      inherent mast cell hyperexcitability observed in canine atopic dermatitis.

PMID- 11844226
TI  - Canine pseudopelade.

PMID- 11844225
TI  - Efficacy of itraconazole as a combined continuous/pulse therapy in feline
      dermatophytosis: preliminary results in nine cases.
AB  - This study evaluated the efficacy of itraconazole as a combined continuous/pulse
      therapy for feline dermatophytosis. Nine cats with dermatophytosis caused by
      Microsporum canis were treated with itraconazole at 10 mg kg(-1) orally once
      daily for 28 days and then on an alternate week regimen (1 week off, 1 week on)
      at the same dosage. Cats were re-evaluated by physical examination and fungal
      culture at days 28, 42, 56 and 70 if necessary. Treatment was stopped when two
      consecutive negative fungal cultures were obtained. Eight cats were cured after
      56 days, with two negative cultures obtained at days 28 and 42. In one case, a
      positive culture was obtained at day 28, but negative cultures were achieved at
      days 42 and 56. This protocol appears to be effective in the treatment of feline
      dermatophytosis, although these preliminary results should be confirmed by a
      controlled study.

PMID- 11844228
TI  - Basilar apex aneurysms: surgical results and perspectives from an initial
      experience.
AB  - OBJECTIVE: To demonstrate that well-trained neurosurgeons can successfully treat
      patients with basilar apex aneurysms, to encourage young neurosurgeons in
      appropriate clinical environments to develop this expertise, and to describe a
      personal experience with an initial series. METHODS: In a consecutive series of
      500 aneurysms treated surgically over 3.5 years, 57 aneurysms in 56 patients were
      located at the basilar apex, 47% of which were large or giant in size. RESULTS:
      Most aneurysms (77%) were treated by direct clipping through an orbitozygomatic
      pterional transsylvian approach. The surgical mortality rate was 9%, and
      permanent neurological morbidity associated with treatment occurred in 5%. Good
      outcomes (Glasgow Outcome Scale score 5 or 4) were achieved in 84%. Good outcomes
      increased from 79% in the first half of the series to 90% in the second half, and
      the mortality rate decreased from 21 to 4%. CONCLUSION: Young neurosurgeons can
      acquire technical proficiency with basilar apex aneurysms while achieving optimal
      patient outcomes. Young neurosurgeons with the right training, talent, and
      temperament are needed to deal with those patients with basilar aneurysms who
      require surgery and with a possible shortage of basilar aneurysm surgeons in the
      future. The learning curve is characterized by increased temporary clipping,
      better perforator dissection, and more sophisticated permanent clipping
      technique. The path to proficiency can be as demanding mentally as it is
      technically.

PMID- 11844229
TI  - Coiling of ruptured pericallosal artery aneurysms.
AB  - OBJECTIVE: To assess the technical feasibility of treating ruptured pericallosal
      artery aneurysms with detachable coils and to evaluate the anatomic and clinical
      results. METHODS: Over a period of 27 months, 12 patients with a ruptured
      pericallosal artery aneurysm were treated with detachable coils. A retrospective
      review was performed to assess the clinical and angiographic results. The three
      men and nine women had a mean age of 46.6 years (range, 35-75 yr). Seven patients
      presented in Hunt and Hess Grade II, three in Grade III, and two in Grade IV. Six
      patients had a concomitant intracerebral hematoma, and four had at least one
      additional aneurysm. RESULTS: In all 12 patients, the pericallosal aneurysm could
      be reached with a microcatheter and the coils delivered. No procedure-related
      complications occurred. Angiography demonstrated that the initial occlusion was
      complete in 11 aneurysms and near-complete in 1. At follow-up angiography at 6
      months, one aneurysm had become partially recanalized owing to coil compaction.
      At a mean clinical follow-up of 9.2 months, 11 patients had an excellent outcome
      and one patient had mild hemiparesis and aphasia. CONCLUSION: Coiling of ruptured
      pericallosal artery aneurysms can be considered an alternative to surgical
      clipping.

PMID- 11844230
TI  - Traumatic intracerebellar hemorrhage: clinicoradiological analysis of 81
      patients.
AB  - OBJECTIVE: We report 81 patients with a traumatic intracerebellar hemorrhagic
      contusion or hematoma managed between 1996 and 1998 at 13 Italian neurosurgical
      centers. METHODS: Each center provided data about patients' clinicoradiological
      findings, management, and outcomes, which were retrospectively reviewed. RESULTS:
      A poor result occurred in 36 patients (44.4%). Forty-five patients (55.6%) had
      favorable results. For the purpose of data analysis, patients were divided into
      two groups according to their admission Glasgow Coma Scale (GCS) scores. In Group
      1 (39/81 cases; GCS score, > or =8), the outcome was favorable in 95% of cases.
      In Group 2 (42/81 cases; GCS score, <8), the outcome was poor in 81% of cases.
      Twenty-seven patients underwent posterior fossa surgery. Factors correlating with
      outcome were GCS score, status of the basal cisterns and the fourth ventricle,
      associated supratentorial traumatic lesions, mechanism of injury, and
      intracerebellar clot size. Multivariate analysis showed significant independent
      prognostic effect only for GCS score (P = 0.000) and the concomitant presence of
      supratentorial lesions (P = 0.0035). CONCLUSION: This study describes
      clinicoradiological findings and prognostic factors regarding traumatic
      cerebellar injury. A general consensus emerged from this analysis that a
      conservative approach can be considered a viable, safe treatment option for
      noncomatose patients with intracerebellar clots measuring less than or equal to 3
      cm, except when associated with other extradural or subdural posterior fossa
      focal lesions. Also, a general consensus was reached that surgery should be
      recommended for all patients with clots larger than 3 cm. The pathogenesis,
      biomechanics, and optimal management criteria of these rare lesions are still
      unclear, and larger observational studies are necessary.

PMID- 11844231
TI  - Can diffusion- and perfusion-weighted magnetic resonance imaging evaluate the
      efficacy of acute thrombolysis in patients with internal carotid artery or middle
      cerebral artery occlusion?
AB  - OBJECTIVE: The value of combined diffusion-weighted imaging (DWI) and perfusion
      weighted imaging (PWI) for detecting ischemic lesions of patients with acute
      ischemic injury was analyzed. Combined pre- and posttreatment DWI and PWI studies
      were used to assess the efficacy of intra-arterial thrombolysis. METHODS: Intra
      arterial thrombolysis was performed within 6 hours of onset in 10 patients who
      presented with acute middle cerebral artery or internal carotid artery occlusion.
      DWI and PWI obtained before and after treatment were studied. The final T2
      weighted magnetic resonance scans were obtained 1 month after onset. Thrombolysis
      resulted in recanalization in seven patients. The mismatch ratio percentage
      ([initial PWI-initial DWI/initial PWI] x 100) and the rescued ratio percentage
      ([initial PWI-final T2/initial PWI] x 100) were calculated. The National
      Institutes of Health Stroke Scale (NIHSS) was used for neurological assessment of
      stroke severity at admission and at 1 month after onset. RESULTS: In all
      patients, the mismatch ratio was greater than 60% (mean +/- standard deviation,
      81.7 +/- 16.7%) and was significantly correlated with initial NIHSS score (-0.74;
      P = 0.03), and the rescued ratio was significantly correlated with the NIHSS
      score 1 month after the insult (r = -0.83; P = 0.01). In patients who exhibited
      recanalization of the occluded artery (n = 7), the mean rescued ratio was 89.6 +/
      12.8% (range, 63-100%). In addition, the lesion volume on posttreatment DWI
      scans and final T2-weighted magnetic resonance images was not enlarged; on
      posttreatment PWI scans, it was significantly decreased. The NHISS score at 1
      month after the insult (2.3 +/- 2.1) was markedly improved as compared with the
      initial NHISS score (10.7 +/- 3.9). CONCLUSION: In a small number of patients who
      presented with internal carotid artery or middle cerebral artery occlusion, the
      DWI/PWI mismatch ratio correlated with the initial neurological severity. The
      rescued ratio may be an objective indicator of the efficacy of treatment.

PMID- 11844232
TI  - Relapse of hyperprolactinemia after transsphenoidal surgery for
      microprolactinoma: lessons from long-term follow-up.
AB  - OBJECTIVE: The long-term results of transsphenoidal surgery for
      microprolactinoma, with particular reference to the question of permanence of
      relapse of hyperprolactinemia after biochemical cure, are examined. METHODS:
      Patients whose operations were performed in the city of Glasgow, Scotland, by one
      neurosurgeon (GMT) have been followed up for between 15 and 21 years after
      surgery was performed. RESULTS: Of a cohort of 44 patients with confirmed
      microprolactinoma at the time of surgery, 8 patients (18.2%) who experienced
      recurrent hyperprolactinemia postoperatively continued to be monitored. Selective
      hypophysectomy resulted in normal prolactin levels in all patients initially.
      Relapse occurred at 2 to 10 years (mean, 5.3 yr) postoperatively, but was
      permanent in only two patients (4.5%). Of the remaining six patients (13.6%),
      four (9.1%) became normoprolactinemic after 6 or 7 years' recurrence, and two
      (4.5%) are now only marginally hyperprolactinemic (prolactin >500 but <700 mU/L)
      at 15 and 18 years after transsphenoidal hypophysectomy. CONCLUSION: The
      recurrence of hyperprolactinemia after transsphenoidal surgery for
      microprolactinoma is not necessarily a permanent feature and does not inevitably
      indicate operative failure.

PMID- 11844233
TI  - Gamma knife stereotactic radiosurgery for patients with glioblastoma multiforme.
AB  - OBJECTIVE: Stereotactic radiosurgery (SRS) has become an effective therapeutic
      modality for the treatment of patients with glioblastoma multiforme (GBM). This
      retrospective review evaluates the impact of SRS delivered on a gamma knife (GK)
      unit as an adjuvant therapy in the management of patients with GBM. METHODS:
      Between August 1993 and December 1998, 82 patients with pathologically confirmed
      GBM received external beam radiotherapy (EBRT) at the University of Maryland
      Medical Center. Of these 82 patients, 64 with a minimum follow-up duration of at
      least 1 month are the focus of this analysis. Of the 64 assessable patients, 33
      patients were treated with EBRT alone (Group 1), and 31 patients received both
      EBRT plus a GK-SRS boost (Group 2). GK-SRS was administered to most patients
      within 6 weeks of the completion of EBRT. The median EBRT dose was 59.7 Gy
      (range, 28-070.2 Gy), and the median GK-SRS dose to the prescription volume was
      17.1 Gy (range, 10-28 Gy). The median age of the study population was 50.4 years,
      and the median pretreatment Karnofsky performance status was 80. Patient-, tumor
      , and treatment-related variables were analyzed by Cox regression analysis, and
      survival curves were generated by the Kaplan-Meier product limit. RESULTS: Median
      overall survival for the entire cohort was 16 months, and the actuarial survival
      rate at 1, 2, and 3 years were 67, 40, and 26%, respectively. When comparing age,
      Karnofsky performance status, extent of resection, and tumor volume, no
      statistical differences where discovered between Group 1 versus Group 2. When
      comparing the overall survival of Group 1 versus Group 2, the median survival was
      13 months versus 25 months, respectively (P = 0.034). Age, Karnofsky performance
      status, and the addition of GK-SRS were all found to be significant predictors of
      overall survival via Cox regression analysis. No acute Grade 3 or Grade 4
      toxicity was encountered. CONCLUSION: The addition of a GK-SRS boost in
      conjunction with surgery and EBRT significantly improved the overall survival
      time in this retrospective series of patients with GBM. A prospective, randomized
      validation of the benefit of SRS awaits the results of the recently completed
      Radiation Therapy Oncology Group's trial RTOG 93-05.

PMID- 11844234
TI  - An analysis of the respective risks of hematoma formation in 361 consecutive
      morphological and functional stereotactic procedures.
AB  - OBJECTIVE: The risk of hematoma formation in stereotactic procedures is generally
      considered to range between 1 and 4%, and it has been speculated that
      morphological procedures may have a higher risk of bleeding than functional
      procedures. METHODS: Between 1989 and 1999, all patients who underwent a
      stereotactic procedure performed by the same surgeon were enrolled sequentially
      onto the study. All patients had normal preoperative prothrombin time, partial
      thromboplastin time, and platelet count. High-resolution computed tomography or
      magnetic resonance imaging with a 1.5-T machine were used for the target
      definition. None of the patients had an angiogram before surgery. RESULTS: A
      total of 361 procedures was performed comprising 175 morphological procedures
      (139 biopsies, 18 lesion evacuations [cysts, abscesses, and hematomas], and 18
      drain implantations) and 186 functional procedures (137 lesions [thalamotomy or
      pallidotomy], 47 deep brain electrode implantations, and two physiological
      explorations without lesions or implantations). There were no infections or
      seizures in either group. Three hematomas (1.7%) occurred in the morphological
      group, two of them in inflammatory lesions in immunocompromised patients (one
      death) and one in a pineal tumor. Three hematomas (1.6%) occurred in the
      functional group (no mortality). There was no statistically significant
      difference (P > 0.05; Fisher's exact test) in the risk of hematoma formation
      between morphological and functional stereotactic procedures. The morbidity and
      mortality related to bleeding also were not statistically different (P > 0.05;
      Fisher's exact test) between these two groups. CONCLUSION: In this series, the
      risk of bleeding was not higher for morphological procedures than for functional
      procedures. This suggests that the risk of bleeding for stereotactic procedures
      is related more to the patient than to the type of procedure performed. Our study
      confirms an overall risk of bleeding of 1.7% for any type of stereotactic
      procedure, resulting in a mortality of 0.3% and a morbidity of 1.4%.

PMID- 11844235
TI  - Neurophysiological refinement of subthalamic nucleus targeting.
AB  - OBJECTIVE: Advances in image-guided stereotactic surgery, microelectrode
      recording techniques, and stimulation technology have been the driving forces
      behind a resurgence in the use of functional neurosurgery for the treatment of
      movement disorders. Despite the dramatic effects of deep brain stimulation (DBS)
      techniques in ameliorating the symptoms of Parkinson's disease, many critical
      questions related to the targeting, effects, and mechanisms of action of DBS
      remain unanswered. In this report, we describe the methods used to localize the
      subthalamic nucleus (STN) and we present the characteristics of encountered
      cells. METHODS: Twenty-six patients with idiopathic Parkinson's disease underwent
      simultaneous, bilateral, microelectrode-refined, DBS electrode implantation into
      the STN. Direct and indirect magnetic resonance imaging-based anatomic targeting
      was used. Cellular activity was analyzed for various neurophysiological
      parameters, including firing rates and interspike intervals. Physiological
      targeting confirmation was obtained by performing macrostimulation through the
      final DBS electrode. RESULTS: The average microelectrode recording time for each
      trajectory was 20 minutes, with a mean of 5.2 trajectories/patient. Typical
      trajectories passed through the anterior thalamus, zona incerta/fields of Forel,
      STN, and substantia nigra-pars reticulata. Each structure exhibited a
      characteristic firing pattern. In particular, recordings from the STN exhibited
      an increase in background activity and an irregular firing pattern, with a mean
      rate of 47 Hz. The mean cell density was 5.6 cells/mm, with an average maximal
      trajectory length of 5.3 mm. Macrostimulation via the DBS electrode yielded mean
      sensory and motor thresholds of 4.2 and 5.7 V, respectively. CONCLUSION: The
      principal objectives of microelectrode recording refinement of anatomic targeting
      are precise identification of the borders of the STN and thus determination of
      its maximal length. Microelectrode recording also allows identification of the
      longest and most lateral segment of the STN, which is our preferred target for
      STN DBS electrode implantation. Macrostimulation via the final DBS electrode is
      then used primarily to establish the side effect profile for postoperative
      stimulation. Microelectrode recording is a helpful targeting adjunct that will
      continue to facilitate our understanding of basal ganglion physiological
      features.

PMID- 11844236
TI  - Elastance correlates with outcome after endoscopic third ventriculostomy in
      adults with hydrocephalus caused by primary aqueductal stenosis.
AB  - OBJECTIVE: To study prospectively the correlation between clinical outcome after
      endoscopic third ventriculostomy (ETV) and resistance to the outflow of
      cerebrospinal fluid (R(out)) and elastance in adults with hydrocephalus caused by
      primary aqueductal stenosis (AS). METHODS: R(out) and elastance were measured in
      the subarachnoid space and intraventricularly before ETV in 15 consecutive
      patients. Three months after the ETV, the clinical effect was evaluated by
      standardized indices, and R(out) and elastance were measured. If symptoms
      persisted and the ETV was patent, shunt surgery was offered. The effect of the
      shunt operation and R(out) were measured after 3 months. RESULTS: Four patients
      experienced excellent improvement, six improved slightly, and five had unchanged
      or deteriorated symptoms after ETV. R(out) before ETV did not correlate with
      outcome. R(out) decreased after ETV with correlation to the clinical effect; in
      the six patients who had shunt surgery, R(out) decreased further. High
      preoperative elastance correlated strongly with a good outcome and reduction of
      ventricle size. Elastance did not change after ETV. CONCLUSION: R(out)
      intraventricularly and in the subarachnoid space could not predict the outcome of
      the ETV, but the reduction in R(out) correlated positively with clinical
      improvement. Preoperative elastance correlated positively with clinical
      improvement, and elastance was unchanged after ETV. Clinical improvement
      correlated positively with reduction in ventricle size.

PMID- 11844237
TI  - Inflammatory mass lesions associated with intrathecal drug infusion catheters:
      report and observations on 41 patients.
AB  - OBJECTIVE: Several reports have described inflammatory mass lesions at the tip of
      intraspinal drug administration catheters. We evaluated the number of patients
      reported with this condition and whether data support hypotheses that have been
      put forth regarding the cause of these lesions. METHODS: Information that was
      reported in the medical literature, and by Medtronic, Inc., to the United States
      Food and Drug Administration as of November 30, 2000, was reviewed. RESULTS:
      Forty-one cases were identified, including 16 from the literature and 25 that
      were not published previously in the literature. Because of voluntary reporting
      and other methodological limitations, the actual number of cases must be higher
      than reported. All of the patients had chronic pain. The mean duration of therapy
      was 24.5 months. Most masses were located in the thoracic region. Intrathecal
      drugs included morphine or hydromorphone, either alone or mixed with other drugs,
      in 39 of 41 cases. No masses were reported in patients who received baclofen as
      the only intrathecal medication. Thirty patients underwent surgery to relieve
      spinal cord or cauda equina compression. Eleven patients were nonambulatory at
      last follow-up, and one died of a pulmonary embolus. Surgical specimens revealed
      noninfectious chronic inflammation, granuloma formation, and fibrosis or
      necrosis. DISCUSSION: The most plausible hypothesis with regard to the cause of
      intrathecal catheter tip mass lesions implicates the administration of relatively
      high-concentration or high-dose opiate drugs or the use of drugs and admixtures
      that are not labeled for intrathecal use. CONCLUSION: Patients who require high
      dose intraspinal opioid therapy and those who receive drugs or admixtures that
      are not approved for intrathecal use should be monitored closely for signs of an
      extra-axial mass or catheter malfunction. Prompt diagnosis and treatment may
      preserve neurological function.

PMID- 11844238
TI  - Combined encephaloduroarteriosynangiosis and bifrontal
      encephalogaleo(periosteal)synangiosis in pediatric moyamoya disease.
AB  - OBJECTIVE: We compared the surgical results of simple
      encephaloduroarteriosynangiosis (EDAS) and EDAS with bifrontal
      encephalogaleo(periosteal)synangiosis for the treatment of pediatric moyamoya
      disease. METHODS: Data for 159 children (up to 15 yr of age, 76 boys and 83
      girls) who underwent indirect revascularization procedures for the treatment of
      moyamoya disease between 1987 and 1998 were retrospectively reviewed. Group A
      patients underwent simple EDAS (n = 67). Group B patients underwent EDAS with
      bifrontal encephalogaleo(periosteal)synangiosis (n = 92). The surgical results
      for each group were compared, in terms of clinical outcomes, neuroimaging
      changes, extent of revascularization evident on angiograms, and hemodynamic
      changes evident on single-photon emission computed tomographic scans. The average
      follow-up periods were 45 months for Group A and 22 months for Group B. RESULTS:
      The overall clinical outcomes and neuroimaging changes tended to be better for
      Group B. In terms of single-photon emission computed tomographic changes of the
      whole brain after surgery, Group B patients exhibited more favorable outcomes
      than did Group A patients (62 versus 36%, P = 0.003). The surgical results for
      the anterior cerebral artery territory were significantly better for Group B than
      for Group A, with respect to outcomes of anterior cerebral artery symptoms (81
      versus 40%, P = 0.015), revascularization on angiograms (79 versus 16%, P <
      0.001), and hemodynamic changes on single-photon emission computed tomographic
      scans (70 versus 52%, P = 0.002). The incidences of postoperative infarctions
      were not significantly different between the two groups. CONCLUSION: EDAS with
      bifrontal encephalogaleo(periosteal)synangiosis is a more effective surgical
      modality for the treatment of pediatric moyamoya disease, compared with simple
      EDAS, because it covers both the middle cerebral artery and anterior cerebral
      artery territories of the brain.

PMID- 11844239
TI  - Laminoplasty with preservation of posterior cervical elements: surgical
      technique.
AB  - OBJECTIVE: We have developed a modified laminoplasty procedure that preserves the
      posterior cervical elements, and we have used it to treat multilevel cervical
      canal stenosis, with or without spondylotic changes, in 30 patients. METHODS: In
      this procedure, the posterior bony elements, such as the spinous processes, are
      not completely detached from the ligaments and musculature and are repositioned
      in the midline, to maintain normal cervical anatomic relationships. Thirty
      patients (mean age, 55.2 yr) were registered and evaluated in this study, with a
      mean follow-up period of 18.1 months, between November 1995 and October 2000. The
      rates of bony union of the reconstructed laminae and alignment of the cervical
      spine were assessed by using computed tomographic scans and lateral radiographs.
      RESULTS: All patients except one noted some improvement in sensation, motor
      function, or both. Changes in spinal curvature were noted for two patients for
      whom a kyphotic deformity had developed before surgery (because of S-shaped or
      straight curvature). The average decrease in the range of motion was 7.26
      degrees. Estimated rates of bony fusion at the sites of the gutters, spacers, and
      spinous processes were 94.6, 62.3, and 86.6%, respectively. A stable bony arch
      was assumed to be achieved with bony fusion at the gutters on the hinge side, as
      well as the spinous processes, approximately 6 months after surgery. CONCLUSION:
      Our new technique of cervical laminoplasty preserves the posterior musculature
      and bony elements. This new procedure also helps maintain correct spinal
      alignment.

PMID- 11844240
TI  - Thoracoscopic microdiscectomy.
AB  - The thorascopic approach for the microsurgical removal of herniated thoracic
      discs is described, and perioperative management is also discussed. The
      microsurgical techniques used for decompression of the spinal canal in the
      thoracic spine are presented in detail. The diagnostic imaging, surgical
      positioning, approach, port placement, localization of the thoracic level,
      exposure of the surgical field, excision of the rib head, exposure with removal
      of the herniated disc, and postoperative management are outlined. Surgical and
      operative "pearls" in thoracoscopic spinal surgery for removing herniated
      thoracic discs when possible are described and illustrated.

PMID- 11844241
TI  - Further study of CD31 protein and messenger ribonucleic acid expression in human
      cerebral vascular malformations.
AB  - OBJECTIVE: In a previous study, we documented lower levels of immunoexpression of
      platelet endothelial cell (EC) adhesion molecule (CD31) in paraffin sections of
      cerebral cavernous malformations (CCMs), compared with arteriovenous
      malformations (AVMs) or normal brain tissue. We hypothesized that down-regulation
      of CD31 in CCMs might represent a distinctive phenotypic feature of ECs in this
      disease. To confirm this hypothesis, we further examined both protein and
      messenger ribonucleic acid (mRNA) expression of CD31, using immunohistochemical
      and in situ hybridization analyses, in fresh-frozen specimens of CCMs, AVMs, and
      control brain tissue. METHODS: Fresh-frozen sections of four AVMs, five CCMs, and
      four control brain tissue specimens obtained from surgical resections were
      immunohistochemically stained with antibodies to von Willebrand factor and two
      distinct epitopes of CD31. In two AVMs, four CCMs, and three control brain tissue
      samples from the aforementioned group, the expression of CD31 mRNA was also
      examined by using in situ hybridization. Large (>100-microm) and small (<100
      microm) vessels were counted and assessed for protein and mRNA expression.
      RESULTS: In all tissues, ECs in the majority of vessels were immunopositive for
      CD31 with two distinct antibodies. CD31 mRNA was expressed in some but not all
      vessels in AVMs, CCMs, and control brain tissue. There were no statistically
      significant differences in CD31 protein or mRNA expression in CCMs, AVMs, and
      control brain tissue. CONCLUSION: The expression of CD31 in CCMs can be
      underestimated in paraffin sections. There does not seem to be a unique
      phenotypic differentiation of CD31 expression in ECs of CCMs or AVMs, compared
      with control brain tissue.

PMID- 11844242
TI  - Expression of vascular endothelial growth factors and their receptors in and
      around intracranial arteriovenous malformations.
AB  - OBJECTIVE: The precise mechanisms responsible for the development and growth of
      intracranial arteriovenous malformations (AVMs) remain unclear, but it has been
      hypothesized that vascular endothelial growth factors (VEGFs) might be involved
      in their pathogenesis. The aim of this study was to examine immunohistochemically
      the presence of the VEGF family (VEGF-A to -D) and their receptors (Flt-1, Flk-1,
      and Flt-4) in the surgically resected AVM nidus. METHODS: The AVM nidus was
      surgically obtained from 31 patients with AVMs (mean age, 40.5 yr, range 13-73
      yr). The mean size of the nidus was 31.6 mm (range, 15-60 mm). Formalin-fixed,
      paraffin-embedded specimens were stained immunohistochemically by the labeled
      streptavidin-biotin method with antibodies against VEGF-A to -D, as well as Flt
      1, Flk-1, and Flt-4. RESULTS: Positive staining for VEGF-A to -D was observed in
      the endothelial cells of the abnormal vessels involved in the AVM nidus and in
      the cytoplasm of astroglia surrounding it. Samples from 30 (96.8%) of 31 patients
      stained positive for VEGF-A, 4 (9.7%) for VEGF-B, 17 (54.5%) for VEGF-C, and 16
      (51.6%) for VEGF-D. Flt-1, Flk-1, and Flt-4 were also positive chiefly, but not
      exclusively, in the cytoplasm of vascular endothelium and smooth muscle cells of
      the vascular wall. With regard to VEGF receptors, it was found that among the 31
      patients studied, 19 (61.3%) were immunohistochemically positive for Flt-1, 6
      (19.4%) for Flk-1, and 19 (61.3%) for Flt-4. A comparison of mean nidus size and
      average age at operation revealed significant differences between patients
      positive for VEGF-C, VEGF-D, Flt-1, or Flt-4. In contrast, there were no
      significant differences in nidus size and age in patients positive for VEGF-A,
      VEGF-B, and Flk-1. CONCLUSION: These results strongly suggest a possible
      contribution of the VEGF-VEGF receptor system to the growth of intracranial AVMs.

PMID- 11844243
TI  - Human endothelin subtype A receptor enhancement during tissue culture via de novo
      transcription.
AB  - OBJECTIVE: Endothelin (ET) has, since its discovery, increasingly been considered
      a key player in the pathophysiological processes of cerebral vasospasm in the
      course of subarachnoid hemorrhage, although it remains unclear how ET is
      involved. We present data that indicate an inherent capacity of human cerebral
      arteries to change their sensitivity to ET. METHODS: Human cerebral arteries were
      obtained from patients undergoing intracranial tumor surgery. The vessels were
      divided into segments and subjected to organ culture for 48 hours. The vessels
      were then examined by using in vitro pharmacological methods and molecular
      biological techniques. RESULTS: After organ culture of the cerebral arteries,
      both the sensitivity to and potency of ET were enhanced (maximal response, 152 +/
      9%; -log (50% effective concentration), 10.3 +/- 0.3), in comparison with data
      for fresh cerebral arteries. Contractions were inhibited by both FR139317 (a
      specific ET(A) receptor antagonist) and bosentan (a mixed ET(A) and ET(B)
      receptor antagonist), in a manner indicating the sole presence of contractile
      ET(A) receptors. An inconsistent dilative response to the selective ET(B)
      receptor agonist sarafotoxin 6c was observed; the response was preserved in some
      segments and abolished in others, and potentiation of the precontraction was
      observed in yet other segments. No isolated contractile response to sarafotoxin
      6c was observed, however. In reverse transcription-polymerase chain reaction
      assays, both ET(A) and ET(B) receptor messenger ribonucleic acid was detected.
      CONCLUSION: These results demonstrate that human cerebral arteries are capable of
      enhancing the function of ET(A) receptors.

PMID- 11844244
TI  - Behavioral and morphological comparison of two nonhuman primate models of
      Huntington's disease.
AB  - OBJECTIVE: Huntington's disease is a progressive neurodegenerative disease
      characterized by movement disorder, cognitive deterioration, and selective
      striatal degeneration. No effective treatment exists, and thus stable primate
      models could aid in the development of novel therapies. METHODS: Two primate
      models of Huntington's disease were analyzed: bilateral stereotactic
      intrastriatal injections of quinolinic acid (QA), and daily systemic
      intramuscular administration of 3-nitropropionic acid (3-NP) for up to 8 weeks in
      male Cebus apella monkeys. The animals' behavior was evaluated before, during,
      and 3 months after administration of the neurotoxin. Magnetic resonance imaging
      scans of the brain were obtained before and after treatment. RESULTS: Frontal
      cognitive function as evaluated by object retrieval-detour task test demonstrated
      a marked deterioration in successful responses, with an increase in barrier
      reaches in both groups. No significant change in performance of fine motor tasks
      was observed. QA-treated animals displayed hyperactivity at night. Animals in
      both groups demonstrated abnormal posture, and the 3-NP-treated group showed
      spontaneous and apomorphine-induced dystonia and dyskinesia. The QA-treated group
      displayed large areas of increased signal on T2-weighted images in the caudate
      and putamen bilaterally. Treatment with 3-NP resulted in smaller lesions.
      Immunohistochemistry and morphometric analyses revealed that both groups had
      lesions in the striatum. A large area of neuronal loss with glial sparing was
      observed in the QA-treated group, including the caudate and putamen bilaterally.
      The 3-NP-treated group displayed smaller lesions restricted to the dorsolateral
      putamen. CONCLUSION: These results suggest that both QA and 3-NP induce
      behavioral and morphological features that resemble the juvenile and akinetic
      rigid variants of Huntington's disease, with the group with 3-NP-induced lesions
      displaying smaller lesions and spontaneous dyskinesia.

PMID- 11844245
TI  - Polyethylene glycol rapidly restores physiological functions in damaged sciatic
      nerves of guinea pigs.
AB  - OBJECTIVE: We have studied the ability of the hydrophilic polymer polyethylene
      glycol (PEG) to anatomically and physiologically reconnect damaged axons of the
      adult guinea pig spinal cord. Here we have extended this approach to test whether
      completely severed guinea pig sciatic nerves in isolation could be fused and
      whether PEG was able to repair severe standardized crush injuries to sciatic
      nerves in vivo. METHODS: The fusion test was performed with isolated sciatic
      nerves maintained in a double-sucrose gap recording chamber. For in vivo
      experiments, the sciatic nerve was surgically exposed in the hind leg of deeply
      anesthetized adult guinea pigs and was crushed proximal to its insertion in the
      gastrocnemius muscle. PEG was injected just beneath the epineurium with a 29
      gauge needle, allowed to remain in the damaged axon region for 2 minutes, and
      removed. Sham-treated guinea pigs received an injection of water or Krebs'
      solution. Three indices of recovery were simultaneously monitored in response to
      electrical stimulation of the proximal nerve, i.e., 1) recovery of compound
      muscle action potentials (in millivolts), 2) contraction force of the muscle (in
      dynes), and 3) displacement of the muscle (in millimeters). RESULTS: When
      isolated sciatic nerves were severed within the double-sucrose gap chamber,
      compound action potential propagation through the transection plane was
      eliminated. After abutment of the two segments and 2-minute PEG application to
      this site, variable compound action potential recovery was measured in all four
      cases. The crush injuries to the sciatic nerve in vivo eliminated the three
      functional responses to sciatic nerve stimulation in all animals. Within the
      first 30 minutes after treatment, only 1 of 12 control animals exhibited
      spontaneous recovery in any of these measures, compared with six of eight PEG
      treated animals. By 45 minutes, two more sham-treated animals and one more PEG
      treated animal had recovered at least one functional response. This difference in
      proportions between PEG-treated and sham-treated animals was statistically
      significant (P < or =0.02). CONCLUSION: We conclude that these preliminary data
      suggest that PEG application may be a way to interfere with the steady
      dissolution of peripheral nerve fibers after mechanical damage and to even
      functionally fuse or reconnect severed proximal and distal segments.

PMID- 11844247
TI  - Adaptation of cerebral circulation to brain arteriovenous malformations increases
      feeding artery pressure and decreases regional hypotension.
AB  - PURPOSE: To determine how the adaptation of extranidal cerebral vessels affects
      feeding artery pressure, draining vein pressure, and regional hypotension due to
      the presence of brain arteriovenous malformations (BAVMs). CONCEPT: BAVMs cause
      high flows in feeding arteries and draining veins and can induce profound
      hypotension in the neighboring vasculature. Despite the large difference in flow,
      endothelial shear stress (tau) observed in vessels ipsilateral to the BAVM is
      similar to tau in vessels contralateral to the BAVM, suggesting that the
      conductance vessels successfully adapt to keep tau constant. However, because
      BAVMs are discovered only after they are well developed, the natural history of
      the adaptation process in extranidal vessels is unknown. RATIONALE: Currently, no
      way exists to determine experimentally the effects of adaptation of extranidal
      vessels in human patients. Therefore, a mathematical model of the cerebral
      vasculature is used to study adaptation in response to BAVMs. By comparing
      pressures and flows calculated before and after adaptation, the effect of
      adaptation of the conductance vessels on regional hemodynamics can be evaluated.
      DISCUSSION: Structural adaptation of the extranidal circulation seems not only to
      reset tau, but also to ameliorate regional hypotension induced by BAVMs. However,
      this compensatory mechanism also increases feeding artery pressure and thus may
      increase the risk of hemorrhagic stroke.

PMID- 11844246
TI  - Dendritic cells pulsed with a tumor-specific peptide induce long-lasting immunity
      and are effective against murine intracerebral melanoma.
AB  - OBJECTIVE: Dendritic cells (DCs) are specialized cells of the immune system that
      are capable of generating potent immune responses that are active even within the
      "immunologically privileged" central nervous system. However, immune responses
      generated by DCs have also been demonstrated to produce clinically significant
      autoimmunity. Targeting the epidermal growth factor receptor variant III
      (EGFRvIII), which is a mutation specific to tumor tissue, could eliminate this
      risk. The purpose of this study was to demonstrate that DC-based immunizations
      directed solely against this tumor-specific antigen, which is commonly found on
      tumors that originate within or metastasize to the brain, could be efficacious.
      METHODS: C3H mice were vaccinated with DCs mixed with a keyhole limpet hemocyanin
      conjugate of the tumor-specific peptide, PEP-3, which spans the EGFRvIII
      mutation, or the random-sequence peptide, PEP-1, and were intracerebrally
      challenged with a syngeneic melanoma expressing a murine homologue of EGFRvIII.
      RESULTS: Systemic immunization with DCs mixed with PEP-3-keyhole limpet
      hemocyanin generated antigen-specific immunity. Among mice challenged with
      intracerebral tumors, this resulted in an approximately 600% increase in the
      median survival time (>300 d, P < 0.0016), relative to control values. Sixty
      three percent of mice treated with DCs mixed with the tumor-specific peptide
      survived in the long term and 100% survived rechallenge with tumor, indicating
      that antitumor immunological memory was also induced. CONCLUSION: In a murine
      melanoma model, immunization with DCs mixed with tumor-specific peptide results
      in an antigen-specific immunological response that recognizes the EGFRvIII
      mutation, has potent antitumor efficacy against intracerebral tumors that express
      EGFRvIII, and results in long-lasting antitumor immunity.

PMID- 11844248
TI  - Lawrence of Arabia, Sir Hugh Cairns, and the origin of motorcycle helmets.
AB  - When Colonel T.E. Lawrence ("Lawrence of Arabia") was fatally injured in a
      motorcycle accident in May 1935, one of the several doctors attending him was a
      young neurosurgeon, Hugh Cairns. He was moved by the tragedy in a way that was to
      have far-reaching consequences. At the beginning of the Second World War, he
      highlighted the unnecessary loss of life among army motorcycle dispatch riders as
      a result of head injuries. His research concluded that the adoption of crash
      helmets as standard by both military and civilian motorcyclists would result in
      considerable saving of life. It was 32 years later, however, that motorcycle
      crash helmets were made compulsory in the United Kingdom. As a consequence of
      treating T.E. Lawrence and through his research at Oxford, Sir Hugh Cairns' work
      largely pioneered legislation for protective headgear by motorcyclists and
      subsequently in the workplace and for many sports worldwide. Over subsequent
      decades, this has saved countless lives.

PMID- 11844249
TI  - A man for all seasons: W.W. Keen.
AB  - William Williams Keen was the catalyst for the advent of neurosurgery in the
      United States. He served in the Civil War and collaborated with Silas Weir
      Mitchell in studying injuries sustained to the nervous system. These studies
      culminated in the publication in 1864 of "Gunshot Wounds and Other Injuries of
      the Nerves and Reflex Paralysis," which first described causalgia, reflex
      sympathetic dystrophy, and secondary paralysis. His most monumental
      accomplishment undoubtedly was being the first surgeon in the United States to
      successfully remove a primary brain tumor (1887) and have the patient survive for
      more than 30 years. As the editor of "Surgery, Its Principles and Practice," Keen
      invited Harvey Cushing to write the section on surgery of the head, which
      propelled Cushing to international recognition and provided a foothold for the
      new specialty of neurosurgery. Multiple sources were reviewed to prepare this
      comprehensive biographical account of Keen's contributions. Emphasis is placed on
      those achievements that furthered the discipline of neurosurgery. Although a
      general surgeon, Keen had a special interest in the nervous system. He treated
      patients with trigeminal neuralgia, performed cortical excisions for patients
      with epilepsy, and devised the procedure of posterior upper cervical root
      sections for spasmodic torticollis. He was the first surgeon to perform and
      advocate ventricular punctures. He served as a consultant and surgeon to both
      Grover Cleveland and Franklin Delano Roosevelt.

PMID- 11844250
TI  - Dandy-Walker complex and syringomyelia in an adult: case report and discussion.
AB  - OBJECTIVE AND IMPORTANCE: Syringomyelia in association with the Dandy-Walker
      complex is rare and only 17 cases have been reported, mostly as autopsy findings
      or incidental reports in series for other conditions. We present a further case
      report and discuss the possible pathogenetic mechanisms of syrinx formation in
      the presence of the Dandy-Walker complex. We emphasize the role of foramen magnum
      obstruction and alteration in cerebrospinal fluid flow dynamics in syrinx
      formation. The therapeutic importance of disimpaction of the foramen magnum is
      stressed. CLINICAL PRESENTATION: A 39-year-old man presented with headache. As a
      child, he had had cystoperitoneal and ventriculoperitoneal shunts inserted for
      hydrocephalus in association with the Dandy-Walker complex. On examination, the
      patient had limited upgaze but was otherwise normal. Magnetic resonance imaging
      revealed a large cervicothoracic syrinx and a Dandy-Walker cyst obstructing the
      foramen magnum. INTERVENTION: The cystoperitoneal shunt was revised. The
      patient's headaches resolved, and follow-up imaging demonstrated resolution of
      the syrinx and disimpaction of the foramen magnum. CONCLUSION: Disimpaction of
      the foramen magnum can resolve syringomyelia in patients with the Dandy-Walker
      complex. This can be achieved by a shunt procedure or by formal foramen magnum
      decompression. The rarity of the association between the Dandy-Walker complex and
      syringomyelia prevents firm conclusions from being made regarding the best
      management strategy for this condition.

PMID- 11844251
TI  - Chronic subdural hematoma complicating arachnoid cyst secondary to soccer-related
      head injury: case report.
AB  - OBJECTIVE AND IMPORTANCE: Soccer has become a popular sport, with more than 200
      million Federation International Football Association-registered soccer players
      worldwide and 16 million participants in the United States. The risk of
      sustaining a significant head injury from a strike to a soccer ball with the head
      is unknown, but it may be increased with the presence of an underlying congenital
      arachnoid cyst. CLINICAL PRESENTATION: We describe the case of a 16-year-old
      female patient who sustained a large chronic and subacute subdural hematoma
      without a loss of consciousness from being struck on the head by a soccer ball.
      Because of the large size of the hematoma and her contralateral symptoms, surgery
      was performed. INTERVENTION: A temporal craniotomy for evacuation of a large
      chronic and subacute subdural hematoma with removal and fenestration of the
      arachnoid cyst resulted in resolution of her symptoms. Rigid craniotomy fixation
      of this small operative flap should allow the patient to return to soccer
      participation in the future. CONCLUSION: Although many may not consider soccer a
      contact sport, recent epidemiological data suggest that it is a common cause of
      sports-related concussion. In addition, as our case report demonstrates, there is
      a risk of significant intracranial injury and hematoma formation subsequent to a
      strike on the head by a soccer ball, and arachnoid cysts may contribute an
      additional risk of head injury.

PMID- 11844252
TI  - Recurrent torticollis caused by dissecting vertebral artery aneurysm in a
      pediatric patient: results of endovascular treatment by use of coil embolization:
      case report.
AB  - OBJECTIVE AND IMPORTANCE: Torticollis is a symptom that can be related to
      different pathological mechanisms ranging from simple to life-threatening
      conditions. We report a child with recurrent torticollis caused by an
      intracranial dissecting vertebral artery aneurysm. This is a very rare condition
      in childhood, and it was resolved successfully with endovascular treatment.
      CLINICAL PRESENTATION: The patient was a 10-year-old boy with a 4-year history of
      left recurrent torticollis, followed by hemiparesis, dysarthria, dysmetria, and
      tremor. Brain magnetic resonance imaging and digital angiography detected a
      dissecting aneurysm involving the fourth segment of the left vertebral artery.
      INTERVENTION: The patient underwent endovascular treatment. Coil embolization,
      followed by histoacryl injection into the lesion, provided complete obliteration
      of the aneurysmal sac. CONCLUSION: The patient's postoperative course was
      characterized by a dramatic disappearance of symptoms and signs within a few
      hours of the intervention. No relapses of symptoms occurred during a follow-up
      period of 18 months. This is the first report of a child in whom recurrent
      torticollis was related to a dissecting vertebral artery aneurysm. Although long
      term results of vertebral artery coil embolization remain to be elucidated, the
      method seems reliable and effective in treatment of these vascular lesions in
      pediatric patients.

PMID- 11844253
TI  - Internal carotid-inferior petrosal sinus fistula complicating foramen ovale
      telemetry: successful treatment with detachable coils: case report and review.
AB  - OBJECTIVE AND IMPORTANCE: Iatrogenic internal carotid artery-cavernous sinus
      fistula complicating percutaneous foramen ovale (FO) instrumentation (e.g.,
      retrogasserian rhizotomy for trigeminal neuralgia) has been reported in only four
      patients to date. To our knowledge, no case of fistula has previously been
      reported either to complicate FO telemetry or to involve the inferior petrosal
      sinus (IPS); moreover, most patients have presented within 48 hours. We present a
      case of internal carotid artery-IPS fistula that complicated FO telemetry in
      which the clinical syndrome was delayed by 4 weeks. CLINICAL PRESENTATION: Four
      weeks after undergoing bilateral FO telemetry during Phase 2 investigations for
      surgery for epilepsy, a 37-year-old man suddenly developed a painful bilateral
      pupil-sparing oculomotor palsy, poor visual acuity, proptosis, conjunctival
      suffusion, and an audible bruit over the right frontotemporal region.
      INTERVENTION: Cerebral angiography demonstrated a high-flow arteriovenous fistula
      between the junction of the petrous and laceral portions of the right internal
      carotid artery and right IPS, with rapid filling of both cavernous sinuses.
      Successful obliteration was obtained with Guglielmi detachable coils, followed by
      complete resolution of the bilateral ocular abnormality. CONCLUSION: This is the
      first reported case of iatrogenic fistula formation to either involve the IPS or
      to complicate FO telemetry. In addition, symptomatology was anomalously delayed.
      This case highlights the importance of noting FO anatomic asymmetries before FO
      instrumentation and of routinely inquiring for "swooshing" noises after electrode
      withdrawal.

PMID- 11844254
TI  - Intravascular graft stent treatment of a ruptured fusiform dissecting aneurysm of
      the intracranial vertebral artery: technical case report.
AB  - OBJECTIVE AND IMPORTANCE: An innovative stenting technique to treat a difficult
      case of a fusiform aneurysm of the intracranial vertebral artery (VA), with
      restoration of the vessel lumen, is described. CLINICAL PRESENTATION: A 58-year
      old patient experienced sudden pain in the upper cervical spine, followed by a
      severe headache. He underwent computed tomographic evaluation, which demonstrated
      subarachnoid hemorrhage in the prepontine cistern. A fusiform aneurysm of the
      distal right VA and critical stenosis of the left VA were detected in digital
      subtraction angiograms. The patient experienced a new subarachnoid hemorrhaging
      episode, and urgent endovascular treatment was planned. INTERVENTION: The patient
      underwent angioplastic and stenting procedures in the left VA, with good results.
      Forty-eight hours later, an endovascular procedure was performed to treat the
      right VA aneurysm. We decided to use a graft stent (Jostent graft stent; Jomed,
      Conroe, TX) instead of a balloon to preserve the arterial lumen. The complete
      procedure was well tolerated by the patient, and he was discharged, without
      symptoms, 48 hours later. CONCLUSION: The patient was discharged, without
      neurological deficits, 48 hours after completion of the endovascular procedure,
      with clopidogrel (75 mg/d) and aspirin (325 mg/d) therapy. This treatment was
      discontinued after 4 weeks. According to our search of the medical literature,
      this is the first clinical case in which an intracranial fusiform aneurysm was
      permanently sealed with a graft stent.

PMID- 11844255
TI  - Repair of a tear at the base of a blister-like aneurysm with suturing and an
      encircling clip: technical note.
AB  - OBJECTIVE: An aneurysm can produce large defects in the parent vessel if the
      aneurysm tears at the neck of the vessel. The authors present a technique to
      repair a tear at the base of a blister-like aneurysm encountered during
      microsurgical clipping of an anterior wall aneurysm of the internal carotid
      artery. METHODS: The repair technique involved suturing and covering the aneurysm
      with an encircling aneurysm clip. A large tear had destroyed the vessel's tubular
      structure, and repair was not sufficient using an encircling clip alone. Two
      microsuture stitches were placed on the tear, so that a split artery re-formed a
      tubular structure. The lesion was then covered with Surgicel (Ethicon, Inc.,
      Somerville, NJ) and fibrin glue. When the Surgicel and fibrin glue were applied,
      the temporary clip on the distal internal carotid artery was removed for a
      moment, allowing retrograde blood flow to provide the counterforce necessary to
      maintain the vessel's tubular structure. An encircling clip was then applied to
      cover the entire circumference of the lesion. RESULTS: This method required only
      a short occlusion time for arterial repair, thus helping avoid ischemic
      complications. The patient awoke with transient hemiparesis, but recovery was
      prompt. CONCLUSION: This technique is useful for repairing an aneurysmal tear at
      its base, especially if the tear is large.

PMID- 11844256
TI  - Surgical simulation software for insertion of pedicle screws.
AB  - OBJECTIVE: As the first step toward finding noninvasive alternatives to the
      traditional methods of surgical training, we have developed a small, stand-alone
      computer program that simulates insertion of pedicle screws in different spinal
      vertebrae (T10-L5). METHODS: We used Delphi 5.0 and DirectX 7.0 extension for
      Microsoft Windows. This is a stand-alone and portable program. RESULTS: The
      program can run on most personal computers. It provides the trainee with visual
      feedback during practice of the technique. At present, it uses predefined three
      dimensional images of the vertebrae, but we are attempting to adapt the program
      to three-dimensional objects based on real computed tomographic scans of the
      patients. The program can be downloaded at no cost from the web site:
      www.tums.ac.ir/downloads CONCLUSION: As a preliminary work, it requires further
      development, particularly toward better visual, auditory, and even proprioceptive
      feedback and use of the individual patient's data.

PMID- 11844257
TI  - Anterior cervical plating enhances arthrodesis after discectomy and fusion with
      cortical allograft.
AB  - OBJECTIVE: Anterior plate fixation has gained widespread acceptance for the
      treatment of cervical spondylosis, theoretically enhancing the rate of
      arthrodesis. There are few studies comparing fusion rates after anterior cervical
      discectomy and fusion (ACDF) with and without a plate. The purpose of this study
      was to evaluate the efficacy of anterior cervical plating for fusion enhancement
      after one- and two-level ACDF with cortical allograft. METHODS: A retrospective
      review was performed with 251 patients who underwent one- or two-level ACDF with
      cortical allograft and plate stabilization between 1993 and 1999. An independent
      surgeon reviewer determined fusion status and complications. A successful fusion
      was defined by the absence of lucency around the graft, evidence of bridging bone
      between the endplate and the graft, and the absence of movement on dynamic
      imaging scans. Follow-up data, ranging from 9 months to 3.6 years, were available
      for 233 patients. A control group of 289 patients who underwent ACDF without
      plating was described in a previously published report by the senior author
      (RWH). Therefore, a total of 540 patients were evaluated for determination of the
      efficacy of anterior cervical plating with cortical allograft bone. Statistical
      significance was determined by chi(2) test. RESULTS: The fusion rates for one-
      and two-level ACDF with anterior fixation were 96 and 91%, respectively, compared
      with 90 and 72% for one- and two-level ACDF without anterior fixation. The
      observed increases in fusion rates for both one- and two-level procedures proved
      to be statistically significant (P < 0.05). There were no recorded infectious,
      neurological, or graft-related complications among the cohort treated with
      anterior cervical plating. Compared with the results for the cohort treated
      without anterior cervical plates, there was a statistically significant decrease
      in the graft-related complication rate with the application of plates (P <
      0.001). Two patients who received plates were noted to have adjacent-segment
      degenerative changes that required surgical intervention. No hardware fractures
      were noted; however, one patient was noted to have a single displaced screw,
      without clinical consequences. CONCLUSION: The use of anterior cervical plating
      after one- and two-level ACDF with allograft cortical bone significantly enhanced
      arthrodesis. The improved fusion rate and negligible complication rate associated
      with anterior cervical plating are compelling factors justifying its use in the
      treatment of cervical spondylosis.

PMID- 11844258
TI  - Follow-up angiography of intracranial aneurysms treated with endovascular
      placement of Guglielmi detachable coils.
AB  - OBJECTIVE: The success of endovascular treatment of intracranial aneurysms with
      Guglielmi detachable coils (GDCs) is dependent on the long-term exclusion of the
      aneurysm from the circulation. We reviewed our experience with the long-term
      angiographic follow-up monitoring of aneurysms that had been treated with GDCs.
      METHODS: All patients whose aneurysms had been treated with GDCs between January
      1995 and August 1999 and who subsequently underwent follow-up angiography at 6
      months or more were included in this study. We reviewed all of the angiographic
      findings, to determine the percentage of aneurysm occlusion on the initial
      angiograms and on the last available follow-up angiograms. The categories of
      aneurysm occlusion used were 100%, >or=95%, and less than 95% occlusion. RESULTS:
      One hundred thirty patients with 141 aneurysms underwent 143 endovascular coiling
      procedures and subsequently underwent angiographic follow-up monitoring of 6
      months or more. There were 102 female and 28 male patients. The mean angiographic
      follow-up period was 16.7 months (range, 6-62 mo). The initial rates of occlusion
      were 100% for 56 aneurysms (39%), >or=95% for 65 aneurysms (46%), and less than
      95% for 22 aneurysms (15%). Recurrence of one aneurysm (1.8%) was observed. Of
      the 87 aneurysms that were incompletely occluded initially, there was progressive
      thrombosis in 40 (46%), stable neck remnants in 23 (26%), and enlargement of the
      residual neck in 24 (28%). The final occlusion rates, determined on the last
      available angiograms, were 100% for 88 aneurysms (61%), >or=95% for 31 aneurysms
      (22%), and less than 95% for 24 aneurysms (17%). No patient experienced repeat or
      new subarachnoid hemorrhage more than 6 months after the initial treatment.
      CONCLUSION: Late angiographic follow-up monitoring of aneurysms that have been
      treated with GDCs demonstrates the durability of the treatment. Aneurysms with
      large residual neck remnants were subjected to further treatment, whereas
      aneurysms with small residual neck remnants remain under observation.

PMID- 11844259
TI  - Endovascular administration after intravenous infusion of thrombolytic agents for
      the treatment of patients with acute ischemic strokes.
AB  - OBJECTIVE: To determine the feasibility of combined intravenous and intra
      arterial thrombolytic therapy for acute ischemic strokes and to evaluate its
      associated risks, using magnetic resonance imaging as a triage tool. Intravenous
      treatment followed by intra-arterial infusion may increase the rate of
      recanalization and lead to better clinical results, with reduced frequency of
      intracranial hemorrhage. METHODS: Our Brain Attack Team evaluated patients who
      presented within 3 hours after symptom onset. Patients who did not demonstrate
      improvement and exhibited no evidence of intracranial hemorrhage on head computed
      tomographic scans were treated with intravenously administered recombinant tissue
      plasminogen activator (0.6 mg/kg) and underwent emergency magnetic resonance
      imaging of the head. T2-weighted turbo-gradient and spin echo and echo-planar
      diffusion- and perfusion-weighted imaging scans were obtained. Patients with
      evidence of imaging abnormalities indicating acute cortical infarction underwent
      cerebral angiography. After determination of vessel occlusion, intra-arterially
      administered urokinase (up to 750,000 units) or intra-arterially administered
      recombinant tissue plasminogen activator (maximal dose, 0.3 mg/kg) was used to
      achieve recanalization. RESULTS: We treated 45 patients with this protocol. The
      mean age was 67 +/- 13 years, and 58% of the patients were women. There was a
      significant improvement in National Institutes of Health Stroke Scale scores
      after treatment. There was good correlation between abnormal perfusion-weighted
      imaging findings and cerebral angiographic findings (complete vessel occlusion).
      The incidence of symptomatic intracranial hemorrhage was 4.4% in this cohort.
      Seven patients died in the hospital, and the majority of survivors (77%)
      experienced good outcomes (Barthel index of >or=95) 3 months after treatment.
      CONCLUSION: Our data demonstrate that this protocol is feasible and that combined
      intravenous and intra-arterial thrombolysis to treat acute ischemic strokes is
      sufficiently safe to warrant further evaluation.

PMID- 11844260
TI  - Traumatic subarachnoid hemorrhage: demographic and clinical study of 750 patients
      from the European brain injury consortium survey of head injuries.
AB  - OBJECTIVE: Previous reports identified the presence of traumatic subarachnoid
      hemorrhage (tSAH) on admission computed tomographic (CT) scans as an independent
      prognostic factor in worsening outcomes. The mechanism underlying the link
      between tSAH and prognosis has not been clarified. The aim of this study was to
      investigate the association between CT evidence of tSAH and outcomes after
      moderate or severe head injuries. METHODS: In a survey organized by the European
      Brain Injury Consortium, data on initial severity, treatment, and subsequent
      outcomes were prospectively collected for 1005 patients with moderate or severe
      head injuries who were admitted to one of the 67 European neurosurgical units
      during a 3-month period in 1995. The CT findings were classified according to the
      Traumatic Coma Data Bank classification system, and the presence or absence of
      tSAH was recorded separately in the initial CT scan forms. RESULTS: Complete data
      on early clinical features, CT findings, and outcomes at 6 months were available
      for 750 patients, of whom 41% exhibited evidence of tSAH on admission CT scans.
      There was a strong, highly statistically significant association between the
      presence of tSAH and poor outcomes. In fact, 41% of patients without tSAH
      achieved the level of good recovery, whereas only 15% of patients with tSAH
      achieved this outcome. Patients with tSAH were significantly older (median age,
      43 yr; standard deviation, 21.1 yr) than those without tSAH (median age, 32 yr;
      standard deviation, 19.5 yr), and there was a significant tendency for patients
      with tSAH to exhibit lower Glasgow Coma Scale scores at the time of admission. A
      logistic regression analysis of favorable/unfavorable outcomes demonstrated that
      there was still a very strong association between tSAH and outcomes after
      simultaneous adjustment for age, Glasgow Coma Scale Motor Scores, and admission
      CT findings (odds ratio, 2.49; 95% confidence interval, 1.74-3.55; P < 0.001).
      Comparison of the time courses for 164 patients with early (within 14 d after
      injury) deaths demonstrated very similar patterns, with an early peak and a
      subsequent decline; there was no evidence of a delayed increase in mortality
      rates for either group of patients (with or without tSAH). CONCLUSION: These
      findings for an unselected series of patients confirm previous reports of the
      adverse prognostic significance of tSAH. The data support the view that death
      among patients with tSAH is related to the severity of the initial mechanical
      damage, rather than to the effects of delayed vasospasm and secondary ischemic
      brain damage.

PMID- 11844261
TI  - Fractionated proton beam radiotherapy for acoustic neuroma.
AB  - OBJECTIVE: This study evaluated proton beam irradiation in patients with acoustic
      neuroma. The aim was to provide maximal local tumor control while minimizing
      complications such as cranial nerve injuries. METHODS: Thirty-one acoustic
      neuromas in 30 patients were treated with proton beam therapy from March 1991 to
      June 1999. The mean tumor volume was 4.3 cm(3). All patients underwent
      pretreatment neurological evaluation, contrast enhanced magnetic resonance
      imaging, and audiometric evaluation. Standard fractionated proton radiotherapy
      was used at daily doses of 1.8 to 2.0 cobalt Gray equivalent: patients with
      useful hearing before treatment (Gardner-Robertson Grade I or II) received 54.0
      cobalt Gray equivalent in 30 fractions; patients without useful hearing received
      60.0 cobalt Gray equivalent in 30 to 33 fractions. RESULTS: Twenty-nine of 30
      patients were assessable for tumor control and cranial nerve injury. Follow-up
      ranged from 7 to 98 months (mean, 34 mo), during which no patients demonstrated
      disease progression on magnetic resonance imaging scans. Eleven patients
      demonstrated radiographic regression. Of the 13 patients with pretreatment
      Gardner-Robertson Grade I or II hearing, 4 (31%) maintained useful hearing. No
      transient or permanent treatment-related trigeminal or facial nerve dysfunction
      was observed. CONCLUSION: Fractionated proton beam therapy provided excellent
      local control of acoustic neuromas when treatment was administered in moderate
      doses. No injuries to the Vth or VIIth cranial nerves were observed. A reduction
      in the tumor dose is being evaluated to increase the hearing preservation rate.

PMID- 11844262
TI  - Cerebellopontine angle epidermoids presenting with cranial nerve hyperactive
      dysfunction: pathogenesis and long-term surgical results in 30 patients.
AB  - OBJECTIVE: To provide the characteristics and long-term surgical results of
      patients who present with cerebellopontine angle epidermoids and trigeminal
      neuralgia (TN) or hemifacial spasm. METHODS: A total of 30 patients (23 women, 7
      men) who presented with cerebellopontine angle epidermoids and TN (28 patients)
      or hemifacial spasm (2 patients) between 1982 and 1995 were reviewed, with
      emphasis being placed on the clinical manifestations, the mechanisms of symptom
      development, the long-term follow-up results, and the anatomic relationship
      between the tumor and the surrounding neurovascular structures. RESULTS: The
      average age of the patients was 37.8 years at symptom onset and 49.3 years at the
      time of the operation. The tumor-nerve relationships were classified into four
      types: complete encasement of the nerve by the tumor, compression and distortion
      of the nerve by the tumor, compression of the nerve by an artery located on the
      opposite side of the unilateral tumor, and compression of the nerve by an artery
      on the same side of the tumor. Total resection was achieved in 17 patients
      (56.7%). Microvascular decompression of the respective cranial nerve was achieved
      in nine cases of direct arterial compression in addition to tumor removal. The
      symptom was relieved completely in all cases. In an average follow-up period of
      11.5 years, three patients developed recurrent symptoms: two experienced tumor
      regrowth, and one had arachnoid adhesion. CONCLUSION: Hyperactive dysfunction of
      the cranial nerves, especially TN, may be the initial and only symptom that
      patients with cerebellopontine angle epidermoids experience. The occurrence of TN
      at a younger age was characteristic of TN patients with epidermoids, in contrast
      to patients with TN due to a vascular cause. The symptom is elicited by
      compression of the nerve by the tumor per se, by an artery that is displaced to
      the nerve, or by both. Careful resection of the tumor, whose capsule occasionally
      is strongly adherent to the neurovascular structures, is necessary, and
      microvascular decompression to straighten the neuraxis should be performed in
      some cases to achieve a complete, permanent cure of symptoms with a low rate of
      recurrence.

PMID- 11844263
TI  - Hyperbaric oxygen treatment of postoperative neurosurgical infections.
AB  - OBJECTIVE: To evaluate the clinical usefulness of hyperbaric oxygen (HBO) therapy
      for neurosurgical infections after craniotomy or laminectomy. METHODS: The study
      involved review of medical records, office visits, and telephone contacts for 39
      consecutive patients who were referred in 1996 to 2000. Infection control and
      healing without removal of bone flaps or foreign material, with a minimum of 6
      months of follow-up monitoring, were considered to represent success. RESULTS:
      Successful results were achieved for 27 of 36 patients, with a mean follow-up
      period of 27 months (range, 6-58 mo). One patient discontinued HBO therapy
      because of claustrophobia, and two could not be evaluated because of death
      resulting from tumor recurrence. In Group 1 (uncomplicated cranial wound
      infections), 12 of 15 patients achieved healing with retention of bone flaps. In
      Group 2 (complicated cranial wound infections, with risk factors such as
      malignancy, radiation injury, repeated surgery, or implants), all except one
      infection resolved; three of four bone flaps and three of six acrylic
      cranioplasties could be retained. In Group 3 (spinal wound infections), all
      infections resolved, five of seven without removal of fixation systems. There
      were no major side effects of HBO treatment. CONCLUSION: HBO treatment is an
      alternative to standard surgical removal of infected bone flaps and is
      particularly useful in complex situations. It can improve outcomes, reduce the
      need for reoperations, and allow infection control without mandatory removal of
      foreign material. HBO therapy is a safe, powerful treatment for postoperative
      cranial and spinal wound infections, it seems cost-effective, and it should be
      included in the neurosurgical armamentarium.

PMID- 11844264
TI  - Somatotopy of the supplementary motor area: evidence from correlation of the
      extent of surgical resection with the clinical patterns of deficit.
AB  - OBJECTIVE: This study, which aimed to confirm or invalidate the somatotopic
      organization of the supplementary motor area (SMA), correlates the pattern of
      clinical symptoms observed after SMA removal with the extent of resection.
      METHODS: Eleven patients with medial precentral glioma underwent partial or
      complete tumoral resection of the SMA. Seven patients underwent preoperative
      functional magnetic resonance imaging that incorporated speech and motor tasks.
      During the operation, the primary motor and speech areas and pathways (in the
      dominant side) were identified by use of intraoperative direct cortical or
      subcortical stimulation, and these areas were respected. RESULTS: SMA resection
      resulted in motor deficits, language deficits, or both; the deficits were always
      regressive, and they corresponded to the SMA syndrome. The topography and
      severity of these deficits were correlated to the extent of the SMA resection.
      The location of the deficit corresponded to SMA somatotopy: the representations
      of the lower limb, the upper limb, the face, and language (in the left-dominant
      SMA) were located from posterior to anterior. This somatotopy was also observed
      with functional magnetic resonance imaging. CONCLUSION: Correlation between
      clinical patterns of deficit and the extent of SMA resection, guided by means of
      pre- and intraoperative functional methods, provides strong arguments in favor of
      somatotopy in this area. This knowledge should allow clinicians to base
      preoperative predictions of the pattern of postsurgical deficit and recovery on
      the planned resection, thus allowing them to inform patients accurately before
      the procedure.

PMID- 11844265
TI  - Biportal thoracoscopic sympathectomy: surgical techniques and clinical results
      for the treatment of hyperhidrosis.
AB  - OBJECTIVE: To describe a bilateral thoracoscopic sympathectomy procedure, using a
      biportal approach, for the treatment of severe hyperhidrosis. METHODS: Between
      May 1996 and September 2000, 103 consecutive patients underwent thoracoscopic
      sympathectomy procedures to treat bilateral hyperhidrosis (206 procedures).
      Operative results, complications, and patient satisfaction were determined by
      reviews of hospital and office charts and by follow-up assessments in the
      outpatient clinic. Long-term results were determined with clinical examinations,
      follow-up office visits, and follow-up questionnaires. RESULTS: Ninety-three
      patients presented with primary palmar hyperhidrosis, eight with primary axillary
      hyperhidrosis, and two with primary craniofacial hyperhidrosis. Rates of complete
      resolution in the primary area affected were 100% in palmar and craniofacial
      cases and 75% in axillary cases. The average length of hospitalization was 1.06
      days, and 96 patients (93.2%) were discharged on or before the end of the first
      postoperative day. Of 59 patients (57.3%) who developed compensatory
      hyperhidrosis, only 11 patients (10.7%) reported that it was bothersome and none
      considered it disabling. All postoperative complications were transient; five
      patients experienced unilateral Horner's syndrome, three patients experienced
      intercostal neuralgia, and two patients required a chest tube after surgery
      because of a pneumothorax. CONCLUSION: Thoracoscopic sympathectomy using a
      biportal approach effectively treats hyperhidrosis and is associated with short
      hospital stays, high patient satisfaction rates, and low rates of compensatory
      hyperhidrosis or other complications.

PMID- 11844266
TI  - Cerebrospinal fluid shunt complications after urological procedures in children
      with myelodysplasia.
AB  - OBJECTIVE: Invasive urological procedures, commonly performed on patients with
      myelodysplasia, may contribute to the occurrence of cerebrospinal fluid shunt
      complications. Shunt complications that occurred after urological procedures in
      children with myelodysplasia were studied. METHODS: Shunt complications occurring
      after urological procedures were examined in 29 patients. Differences between
      patients with or without complications were studied. Complications were analyzed
      according to the location of abnormality, the treatment, and the timing after
      shunt and urological surgery. RESULTS: The 1-year incidence of shunt
      complications after a urological procedure had been performed was 31% (overall
      incidence, 41.4%). Shunt complications were observed only after intraperitoneal
      urological procedures. Most complications were distal, occurring more than 1 year
      after the preceding shunt surgery. The patients in the shunt complications group
      had significantly more intraperitoneal urological procedures (3.2 versus 0.8, P =
      0.004) and previous shunt revisions (2.0 versus 0.9, P = 0.015) than had the
      group without complications. As compared with the group of patients with
      extraperitoneal complications, the intraperitoneal group experienced
      significantly more infections (4 of 9 versus 0 of 10, P = 0.014) requiring more
      complex treatment, and their complications occurred significantly earlier in the
      follow-up period after the urological procedure had been performed (7.2 versus
      27.3 mo, P = 0.006). The patients in the group with extraperitoneal complications
      experienced significantly more mechanical shunt malfunctions than did the
      intraperitoneal group (9 of 10 versus 4 of 9, P = 0.016), which required simple
      shunt revisions. CONCLUSION: Patients with spina bifida and shunted hydrocephalus
      may have an increased risk of developing intraperitoneal shunt complications
      after intraperitoneal urological procedures have been performed. These
      intraperitoneal shunt complications usually occur a few months after urological
      surgery and require complex treatment.

PMID- 11844267
TI  - Cerebral revascularization for aneurysms and tumors.
AB  - OBJECTIVE: To discuss the indications, techniques, pitfalls, complication
      avoidance, and management of cerebral revascularization techniques for the
      treatment of aneurysms and cranial base tumors. METHODS: The indications for
      cerebral revascularization procedures included microsurgical occlusion of a
      parent vessel during the treatment of aneurysms and occlusion of a major vessel
      during the treatment of basal tumors. The techniques discussed include arterial
      patch grafting, end-to-end anastomosis, side-to-side anastomosis, arterial
      interposition grafting, and extracranial-to-intracranial bypass grafting, using
      radial artery grafts or saphenous vein grafts. RESULTS: During the 15-year period
      between 1985 and 2000, the senior author performed 24 radial artery grafts, 105
      saphenous vein grafts, and 8 other revascularization procedures, among 50
      patients with aneurysms and 83 patients with cranial base tumors. The overall
      patency rate was 95.6%. Twenty-three patients experienced a cerebral infarction;
      among those patients, 17 (12.5%) exhibited symptoms but the majority demonstrated
      considerable recovery during the follow-up period. One hundred one patients
      recovered to an excellent (Glasgow Outcome Scale score of 5) or good (Glasgow
      Outcome Scale score of 4) condition. Fifteen patients died as a result of
      recurrence or progression of tumors during the follow-up period. There were five
      perioperative deaths. For the last 35 patients, the surgical mortality rate was
      0%, with all patients returning to an excellent or good condition. CONCLUSION:
      Although highly specialized, these sophisticated cerebral revascularization
      techniques should be learned and practiced by all neurosurgeons who wish to
      microsurgically treat intracranial aneurysms or cranial base tumors.

PMID- 11844268
TI  - Hemihypoglossal nerve transfer in brachial plexus repair: technique and results.
AB  - OBJECTIVE: In multiple avulsions of the brachial plexus, the search for
      extraplexal donor nerves in the hope of achieving motor neurotization is a major
      goal. We explored the possibility of using the hypoglossal nerve as a transfer
      point to reanimate muscles in the upper limb. METHODS: The hypoglossal nerve was
      used as a donor nerve for neurotization in seven patients with avulsive injuries
      of the brachial plexus. The surgical technique--an end-to-side microsuture using
      approximately half of the nerve fascicles--is basically the same as that used in
      the hypoglossal nerve-facial nerve jump graft, which is a well-known technique in
      facial nerve reanimation. The recipient nerves were the suprascapular (two
      patients), the musculocutaneous (one patient), the posterior division of the
      upper trunk (two patients), and the medial contribution to the median nerve (two
      patients). RESULTS: In spite of a connection documented by electromyography and
      selective activation in three of seven patients, the functional results in our
      patients were extremely disappointing: no patient had an outcome better than M1
      in the reinnervated muscles. CONCLUSION: This technique was of no help to the
      patients and thus has been abandoned at our institution.

PMID- 11844269
TI  - Timing of aneurysm surgery in subarachnoid hemorrhage: a systematic review of the
      literature.
AB  - OBJECTIVE: Many practitioners favor early operation after aneurysmal rupture, but
      sound data supporting this practice are lacking. A systematic review was
      conducted to compare early aneurysm surgery (Days 0-3), intermediate surgery
      (Days 4-7), and late surgery (more than 7 d after subarachnoid hemorrhage).
      METHODS: We performed a MEDLINE search of the literature published between
      January 1974 and December 1998 and an additional manual search of selected
      journal titles from January 1998 to December 1998. Main outcome measures were
      death and poor outcome (defined as death or dependency) at the end of the follow
      up period. Risk ratios (RRs) and corresponding 95% confidence intervals (CIs)
      were calculated; patients planned for late surgery were used as the reference.
      RESULTS: Identified were 1 randomized clinical trial and 268 observational
      studies, of which only 10 studies (assessing a total of 1814 patients) fulfilled
      a set of minimum requirements for methodological quality. In the trial, the RR of
      poor outcome was 0.42 (95% CI, 0.17-1.04) for patients planned for early surgery
      and 1.07 (95% CI, 0.56-2.05) for intermediate surgery. In analyses with data from
      the 11 included studies, the RR of poor outcome for patients in good clinical
      condition at admission was 0.41 (95% CI, 0.34-0.51) for early surgery and 0.47
      (95% CI, 0.32-0.69) for intermediate surgery. For patients in poor clinical
      condition at admission, the RR of poor outcome was 0.84 (95% CI, 0.67-1.05) for
      early surgery and 0.54 (95% CI, 0.24-1.22) for intermediate surgery. Adjustment
      of the RRs for year of publication, study design, and aneurysm location yielded
      essentially the same results, as did a sensitivity analysis after exclusion of
      the data from the randomized trial. CONCLUSION: This meta-analysis suggests that
      both early and intermediate surgical treatment improve outcome after aneurysmal
      subarachnoid hemorrhage--in particular for patients in good clinical condition at
      admission. However, this impression is derived only from an indirect comparison
      between different cohorts of patients. Sound evidence on the best timing of
      surgery is still lacking. Observational studies with better methods--and ideally
      a new randomized trial--are needed.

PMID- 11844270
TI  - Thromboxane synthase inhibitors induce apoptosis in migration-arrested glioma
      cells.
AB  - OBJECTIVE: Because of the wide dissemination of malignant glioma cells by the
      time that malignant glioma is diagnosed, anti-invasive strategies that are
      designed to limit their further spread may be of little value unless mechanisms
      of the invasive cascade can be used to render invasive cells susceptible to
      cytoreductive treatments. We recently determined that elevated thromboxane
      synthase gene expression and enzymatic activity are associated with a highly
      migratory phenotype of glioma cells in vitro and that specific inhibitors of this
      enzyme block cell migration. Interference with this inherent phenotype of
      malignant gliomas also affects glioma cell proliferation and apoptosis. METHODS:
      To study the effect of thromboxane synthase inhibitors on motility, metabolic
      activity, and cell death, we used five human glioma cell lines, four glioblastoma
      derived, low-passage cell cultures, normal human astrocytes, and fibroblasts.
      Motility was measured in a monolayer migration assay. Caspase activation as an
      early event in apoptotic cell death was assessed using a caspase 3 cleavage
      assay. Intracellular deoxyribonucleic acid (DNA) fragmentation was detected by
      enzyme-linked immunosorbent assay quantification of histone-complexed DNA.
      Subsequent cell death was scored by trypan blue exclusion. RESULTS: In this
      study, we demonstrate that the treatment of human glioma cells with the specific
      thromboxane synthase inhibitor furegrelate leads first to caspase activation
      (detectable 6 h after treatment), then to DNA fragmentation (24-48 h after
      treatment) and subsequent cell death. Caspase inhibitors abrogate this effect.
      Furthermore, the inhibition of thromboxane synthase by furegrelate increases
      cells' susceptibility to the induction of DNA fragmentation by camptothecin,
      etoposide, N,N'-bis(2-chloroethyl)-N-nitrosourea, and anti-CD95 antibodies. No
      induction of apoptosis was observed in normal astrocytes and fibroblasts.
      CONCLUSION: These data indicate that thromboxane synthase may represent a vortex
      of divergent signaling cascades that regulate motility and apoptosis in glioma
      cells. This paradigm may offer a novel perspective in the treatment of patients
      with malignant gliomas.

PMID- 11844271
TI  - Somatotopic organization of the facial nucleus is disrupted after lesioning and
      regeneration of the facial nerve: the histological representation of synkinesis.
AB  - OBJECTIVE: After facial nerve repair, involuntary movement of part of the face
      during voluntary movement of another part of the face is common. We describe an
      animal model of facial nerve lesion, repair, and regeneration that demonstrates
      abnormal organization of the facial nucleus; this model may be used to study
      synkinesis. METHODS: In 18 rats, the facial nerve was cut completely, proximal to
      the parotid gland, and immediately sutured end-to-end. After a period of
      regeneration of 1 to 10 months, retrograde fluorescence labeling of the distal
      branches of the facial nerve was performed. The distribution of the tracers in
      the facial nucleus was assessed in both the lesioned animals and in a nonlesioned
      group (n = 20). RESULTS: In the control animals, muscle groups were
      somatotopically represented in the facial nucleus. After lesioning, repair, and
      regeneration, the somatotopy of the facial nucleus was disrupted. Axons projected
      from the facial nucleus to incorrect peripheral muscle groups, and aberrant
      branches were observed to simultaneously innervate different subdivisions of the
      facial nerve. The numbers of aberrant axons and branches did not change
      significantly during periods of regeneration ranging from 1 to 10 months.
      CONCLUSION: Our model provides a clear demonstration of the failure of adult
      facial nerve axons to make correct connections with their distal targets during
      regeneration. This model may be used to assess strategies aimed at minimizing
      synkinesis and, by assessing histology together with behavior, provides a more
      robust model than those previously described.

PMID- 11844272
TI  - Safety and performance of a novel intravascular catheter for induction and
      reversal of hypothermia in a porcine model.
AB  - OBJECTIVE: This study was undertaken to assess the acute safety and feasibility
      of rapidly inducing, maintaining, then reversing hypothermia using a novel heat
      transfer catheter and a closed-loop automatic feedback temperature control system
      to overcome limitations imposed by current clinical practices used for
      perioperative cooling and warming. METHODS: Six swine (mean mass, 53.8 +/- 3.6
      kg) were studied. The heat transfer catheter was placed in the inferior vena cava
      via the femoral vein. Hypothermia to 32 degrees C was induced, maintained for 6
      hours, then reversed to 36 degrees C. The time needed to induce and reverse
      hypothermia was recorded via continuous temperature monitoring of the lower
      esophagus, cerebrum, and rectum. Electrocardiography provided continuous
      monitoring, and blood draws were made at baseline and at 2-hour intervals.
      Examination of the catheter in situ was performed after the animals were killed.
      RESULTS: Cooling from 36.2 to 32.0 degrees C was rapid and uniform (mean, 7.3 +/-
      0.7 degrees C/h), with animals reaching the target temperature within 60 minutes.
      Rewarming was also easily controlled, with animals' temperatures reaching 36
      degrees C within 130 minutes. No arrhythmia was observed, and all hematological
      variables were within the normal range for swine. There was no evidence of
      hemolysis or platelet changes. Little to no thrombosis was observed. CONCLUSION:
      The data presented here suggest that rapid induction and reversal of hypothermia
      are technically possible using a core intravenous cooling catheter; this method
      would provide a safe, rapid, and exquisitely reproducible way to induce
      hypothermia with subsequent restoration of normothermia.

PMID- 11844273
TI  - Role of nitric oxide in the regulation of spinal arteriolar tone.
AB  - OBJECTIVE: The important role played by nitric oxide (NO) in the maintenance of
      cerebral arterial tone, both in the resting state and after injury, has been
      demonstrated, but the role of NO in spinal arteries is unknown. The aim of this
      study was to verify, by topical application of a NO synthase inhibitor in vivo,
      the hypothesis that NO plays an important role in the maintenance of spinal
      arteriolar tone. METHODS: Closed spinal windows were prepared at the C6 level,
      for observation of arteriolar reactivity. Male Wistar rats were divided into four
      groups in the resting state and three groups in the compressed state (which was
      produced by increasing the intrathecal window pressure). The control group
      underwent superfusion of artificial cerebrospinal fluid into the spinal window.
      The nitro-L-arginine-methyl ester (L-NAME) and nitro-D-arginine-methyl ester
      groups underwent superfusion of the NO synthase inhibitor L-NAME and its inactive
      enantiomer nitro-d-arginine-methyl ester, respectively. The L-NAME/S-nitroso
      acetylpenicillamine (SNAP) group underwent mixed superfusion of L-NAME and the
      direct NO donor SNAP, for investigation of the effects of an exogenous NO donor.
      RESULTS: In the resting state, the arterioles constricted significantly in the L
      NAME group, compared with values before L-NAME superfusion and those for the
      other groups. In the L-NAME/SNAP group, the arterioles dilated significantly
      after SNAP superfusion, compared with values before superfusion and those for the
      other groups. In the compressed state, the arterioles dilated after compression
      in all three groups but the dilation was significantly attenuated in the L-NAME
      group, compared with values for the control and nitro-D-arginine-methyl ester
      groups. CONCLUSION: It is suggested that NO plays an important role in the
      maintenance of spinal arteriolar tone in the resting and compressed states of the
      spinal cord.

PMID- 11844275
TI  - A flask full of jelly: the first in vitro model of concussive head injury--1830.
AB  - IN 1830, THE French Military Surgeon Jean-Pierre Gama reported an experiment
      planned to unravel the mechanical events caused by head injury. His model was a
      round glass flask with a long neck filled with a gelatinous substance that
      resembled the consistency of the brain. Thumping the walls of the flask caused
      the movement of thin wires embedded in the "brain-like" material, thought to
      represent the spread of forces within the brain. Gama thought that he could thus
      observe oscillatory and vibratory movements of the wires representing the effects
      of concussion without visible structural brain lesions. Although it was crudely
      constructed, entirely subjective as to evaluation of results, and lacking the
      essential instrumentation that only modern technology can provide, this
      hypothesis-driven pioneer experiment should be regarded as the first to use the
      novel approach of physical modeling of the brain. Even today, this approach has
      not been fully exploited.

PMID- 11844274
TI  - Histological findings in coil-packed experimental aneurysms 3 months after
      embolization.
AB  - OBJECTIVE: Knowledge regarding tissue reactions within coil-packed aneurysms is
      poor. The purpose of this study was to analyze histological changes in a chronic
      experimental bifurcation aneurysm model that might explain the protective effect
      of Guglielmi detachable coils. METHODS: The aneurysms were produced by means of a
      venous graft pouch at a surgically created bifurcation of the carotid artery in
      the neck of rabbits. After 3 weeks, embolization with Guglielmi detachable coils
      was performed in the treatment group but not in the control group (seven rabbits
      each). At the time of embolization, six of seven treated aneurysms were
      completely occluded according to radiological criteria. Twelve weeks later, all
      aneurysms were explanted after final angiography. Histological examinations were
      performed with coils in situ. RESULTS: Six of seven embolized aneurysms
      demonstrated complete occlusion in final angiography. But gross pathology
      revealed that all specimens had differently sized open cavities between the
      coils. In only two cases, these spaces were very small and the aneurysmal sacs
      were filled with coils and tissue by more than 90%. Light microscopy demonstrated
      intraluminal granulation tissue and strong chronic inflammatory wall thickening
      with numerous foreign body cells at the interface between coils and tissue. Coils
      were partially incorporated into the aneurysmal wall, sometimes close to the
      surface and occasionally even outside the wall within the surrounding tissue.
      CONCLUSION: The protective effect of Guglielmi detachable coil treatment in our
      chronic experimental bifurcation aneurysms results from formation of intraluminal
      granulation tissue and wall thickening attributable to chronic inflammation.

PMID- 11844276
TI  - Peripheral aneurysms of the lateral posterior choroidal artery: clinical
      presentation and endovascular treatment: report of two cases.
AB  - OBJECTIVE AND IMPORTANCE: To describe the clinical presentation and endovascular
      management of peripheral aneurysms of the lateral posterior choroidal artery.
      Aneurysms in this location are exceptionally rare and optimal treatment may be
      difficult. CLINICAL PRESENTATION: Two patients with peripheral aneurysms of the
      distal portion of the lateral posterior choroidal artery presented with headaches
      from extensive intraventricular hemorrhage. INTERVENTION: Endovascular surgical
      therapy by use of superselective n-butylcyanoacrylate embolization of the
      aneurysm and adjacent distal parent artery was successful in both patients.
      CONCLUSION: Patients with peripheral aneurysms of the lateral posterior choroidal
      artery usually present with intraventricular hemorrhage. They may be difficult to
      treat by open surgical techniques owing to their intraventricular location and
      the frequent inability to preserve the parent artery by aneurysm clipping.
      Instead, it is typical that either proximal parent artery occlusion or aneurysm
      trapping must be used. An equivalent endovascular surgical technique may be an
      attractive alternative method of management.

PMID- 11844277
TI  - Castleman's disease and spinal cord compression: case report.
AB  - OBJECTIVE AND IMPORTANCE: Castleman's disease is a rare lymphoproliferative
      disorder most often found in the mediastinum. Localized forms are usually benign,
      whereas multicentric forms may be aggressive. We report a patient with
      Castleman's disease who presented with spinal cord compression, and we review
      previously published cases of Castleman's disease involving the central nervous
      system. To our knowledge, this is only the second case of Castleman's disease
      presenting as a spinal epidural mass with cord compression. CLINICAL
      PRESENTATION: A 44-year-old otherwise healthy woman presented acutely with
      difficulty walking. Examination revealed mild myelopathy in her legs. Magnetic
      resonance imaging revealed a posterior epidural mass compressing the thoracic
      spinal cord at T3-T5. INTERVENTION: Thoracic laminectomy and gross total
      resection of the lesion were performed. Pathological examination of the lesion
      identified the hyaline-vascular type of Castleman's disease. The patient's
      symptoms resolved postoperatively. CONCLUSION: Castleman's disease presenting as
      a spinal epidural mass lesion with cord compression is rare. Surgical treatment
      can result in an excellent outcome.

PMID- 11844278
TI  - Fluorodeoxyglucose and methionine uptake in Lhermitte-Duclos disease: case
      report.
AB  - OBJECTIVE AND IMPORTANCE: Lhermitte-Duclos disease (LDD) represents a focally
      indolent dysplastic growth of the cerebellar cortex. The 106 cases reported
      previously in the literature show an extremely slow evolution, and the operative
      indications and techniques for this disease entity are still controversial. The
      authors present the first case of LDD studied with positron emission tomography
      using the labeled tracers [(18)F]2-fluoro-2-deoxy-d-glucose ([(18)F]FDG) and
      (11)C-labeled methionine ([(11)C]Met) to study the glucose and protein metabolism
      of the lesion. CLINICAL PRESENTATION: A 40-year-old woman suddenly became
      unconscious then completely recovered 5 minutes later. Magnetic resonance imaging
      of her brain showed a well-delineated 10 x 5-cm abnormal area with enlarged
      cerebellar folia, which led to the diagnosis of LDD. TECHNIQUE: On positron
      emission tomographic scans, [(18)F]FDG and [(11)C]Met uptake in the normal
      cerebral and cerebellar cortex appeared higher than normal, reaching levels found
      in patients with primary malignant brain tumors. Moreover, the uptake of both
      tracers was heterogeneous, in contrast to the homogeneous uptake visualized on
      magnetic resonance imaging scans. The areas of greatest [(11)C]Met and [(18)F]FDG
      uptake were discordant. Some areas of greater than normal [(18)F]FDG uptake
      corresponded to areas of moderate or low [(11)C]Met uptake. Because of the
      important mass effect in the posterior fossa, total surgical resection was
      performed. A histological examination confirmed the diagnosis of LDD. CONCLUSION:
      This first reported metabolic study of LDD supports the view that LDD is an
      active and evolving disease. These data should prompt reevaluation of the
      indications for surgery in patients with this disease as well as the timing of
      surgery.

PMID- 11844279
TI  - Chondromyxoid fibroma of the cervical spine: case report.
AB  - OBJECTIVE AND IMPORTANCE: The clinical, pathological, and imaging findings in a
      patient with a chondromyxoid fibroma involving the C2 vertebra are reported.
      Seven cases that involve the cervical spine have previously been reported in the
      literature; the posterior vertebral body and posterior elements are the most
      frequently involved. To our knowledge, this is the first reported case of C2
      involvement and craniocervical instability. CLINICAL PRESENTATION: A 20-year-old
      man presented with intermittent neck pain resulting from a fall 4 years earlier.
      X-rays and magnetic resonance imaging demonstrated a lytic lesion in the body of
      C2, as well as instability at C1-C2. INTERVENTION: Preoperative transcatheter
      angiography and embolization were performed. An expansile tumor of the C2
      vertebral body was resected via a transoral approach. Because of craniocervical
      instability, fusion from the occiput to posterior elements of C1 through C4 was
      performed. CONCLUSION: Chondromyxoid fibroma is a rare benign bone tumor that is
      uncommonly found in the spine and may mimic other lesions, particularly
      radiographically. We report the first known involvement of C2 by this tumor in
      the modern English-language literature. The patient has had excellent clinical
      and radiographic resolution of the prior instability with no neck pain,
      instability, or local recurrence.

PMID- 11844280
TI  - Postoperative edema after vascular access causing nerve compression secondary to
      the presence of a perineuronal lipoma: case report.
AB  - OBJECTIVE AND IMPORTANCE: Median nerve neuropathy can be clinically devastating
      to a patient. It can be caused by compression of the median nerve anywhere along
      its course. We present the case of delayed median nerve neuropathy after the
      placement of a vascular graft in the arm. CLINICAL PRESENTATION: An arm shunt was
      placed in the nondominant upper extremity in a 60-year-old man with end-stage
      renal disease. Twelve hours postoperatively, the patient developed neurapraxia in
      the median nerve distribution in the hand. INTERVENTION: Exploration of the arm
      revealed a lipoma coursing along and deep to the median nerve. Resection of the
      lipoma decompressed the nerve. CONCLUSION: In this patient, median nerve
      neuropathy was caused by a lipoma and postoperative swelling from placement of
      the vascular graft. The swelling that occurred after the shunt placement unmasked
      subclinical compression of the nerve by a lipoma deep to the median nerve. To our
      knowledge, this report is unique in documenting damage to the median nerve after
      vascular graft placement as a result of an occult mass.

PMID- 11844281
TI  - Construction of a new posterior communicating artery in a patient with poor
      posterior fossa circulation: technical case report.
AB  - OBJECTIVE AND IMPORTANCE: The carotid and the vertebrobasilar circulation were
      connected, effectively creating a new posterior communicating artery (PComA). The
      excimer laser-assisted nonocclusive anastomosis technique is a new anastomosis
      technique whereby formerly untreatable patients may be treated with an
      intracranial artery-to-intracranial artery bypass procedure. This report is the
      first one in which an angiographically proved patent internal carotid artery
      posterior cerebral artery segment P1 bypass is presented. CLINICAL PRESENTATION:
      Our patient presented with repeated episodes of vertebrobasilar ischemia because
      of vertebral artery occlusion and stenosis. INTERVENTION: An internal carotid
      artery-posterior cerebral artery segment P1 bypass procedure was performed.
      Because the patient experienced transient ischemia in the left cerebral
      hemisphere at the end of postoperative angiography procedure, no radiological
      intervention was performed, and the patient refused to undergo a new radiological
      intervention at a later stage. TECHNIQUES: Both anastomoses were made using the
      excimer laser-assisted nonocclusive anastomosis technique. CONCLUSION:
      Intraoperative flowmetry was performed using an ultrasound flowmeter, which
      disclosed blood flow of 35 ml/min through the bypass. We hope that this new PComA
      suffices to protect the patient from infarction in the territory of the
      vertebrobasilar circulation.

PMID- 11844282
TI  - Use of intraventricular tissue plasminogen activator and Guglielmi detachable
      coiling for the acute treatment of casted ventricles from cerebral aneurysm
      hemorrhage: two technical case reports.
AB  - OBJECTIVE AND IMPORTANCE: We report two cases of massive intraventricular
      hemorrhage resulting from subarachnoid hemorrhage. Both patients had experienced
      a ruptured cerebral aneurysm and were initially moribund. The patients were
      treated with Guglielmi detachable coiling and then administration of
      intraventricular tissue plasminogen activator (tPA). Rapid clot resolution was
      demonstrated radiographically in both. Both patients survived and had a
      meaningful functional neurological recovery. These are the first reported cases
      of the acute use of intraventricular tPA after Guglielmi detachable coiling
      treatment for ruptured cerebral aneurysm. CLINICAL PRESENTATION: A 59-year-old
      woman and a 44-year-old man presented with high-grade subarachnoid hemorrhage.
      Both had had extensive casting of their ventricular systems with blood.
      INTERVENTION: The patients were treated with Guglielmi detachable coiling
      thrombosis of the aneurysm and then intraventricular administration of tPA for
      dissolution of blood clots. Both patients survived; one is able to carry out
      activities of daily living with moderate assistance, and the other is able to
      communicate with his family. CONCLUSION: This is a novel method to manage
      patients with high-grade aneurysms with massive intraventricular blood clots. The
      tPA reduced the mass effect of the blood clot, possibly helping to improve the
      neurological grade; in addition, the administration of tPA helped keep the
      external ventricular drains functional, enabling treatment of the acute
      hydrocephalus. The safety of administering tPA after endovascular thrombosis was
      demonstrated in these two patients. Further investigation is required to
      determine the applicability of this approach on a broader scale.

PMID- 11844283
TI  - C1-C2 pedicle screw fixation with rigid cantilever beam construct: case report
      and technical note.
AB  - OBJECTIVE AND IMPORTANCE: Transarticular screw fixation of the C1-C2 complex
      provides immediate rigid fixation of the unstable spine. The technique is not
      feasible in a certain proportion of patients because of the position of the
      vertebral artery or the patient's body habitus. CLINICAL PRESENTATION: The
      authors describe a rigid screw technique for the surgical treatment of a woman
      who was excluded as a candidate for C1-C2 transarticular screw fixation.
      TECHNIQUE: C1-C2 pedicle screw fixation was achieved using a fixed moment arm
      cantilever beam system. This system provided immediate rigid fixation of the C1
      C2 complex in a patient who was not a candidate for transarticular screw
      fixation. CONCLUSION: This technique is technically more forgiving than posterior
      transarticular screw fixation and may be applied to a broader spectrum of
      patients.

PMID- 11844284
TI  - New era for digital ECG: FDA requires digital ECG submission for tested drugs.

PMID- 11844285
TI  - Weighing the QT intervals with the slope or the amplitude of the T wave.
AB  - OBJECTIVE: The reproducibility of QT interval measurements is low, even for the
      mean QT interval based on the standard ECG. In this study we analyzed whether the
      reproducibility of the mean weighed QT interval was better than the simple mean
      QT interval. The weighing was based on the amplitude of the T wave or the slope
      of the steepest tangent on the terminal part of the T wave. MATERIAL AND METHODS:
      12-lead ECGs of 130 postmyocardial infarction patients were obtained. The QT
      intervals were measured by the tangent-method on two occasions by the same
      observer Mismatch QT intervals were defined as QT intervals that were measured at
      only one occasion. Sixteen ECGs were rejected. The data were split into 34 and 80
      ECGs for optimization and validation of the weighing, respectively. The weighed
      QT dispersion was calculated as the weighed mean of the three longest minus the
      weighed mean of the three shortest QT intervals. RESULTS: Weighing with the slope
      increased the reproducibility by 41% (P = 3 10(-6)), but weighing with the
      amplitude reduced it by 20% (P = 0.02). However, if measurements with errors
      above 75 ms were rejected, weighing with the slope or the amplitude increased the
      reproducibility with 26% and 20% (P = 0.02), respectively. Weighing did not
      change the reproducibility of the weighed QT dispersion. CONCLUSION: Weighing
      with the slope improved the reproducibility of the mean weighed QT interval.
      However, if measurements with errors above 75 ms were rejected, weighing with the
      amplitude also increased the reproducibility. Weighing did not change the
      reproducibility of the weighed QT dispersion. Weighing is particularly efficient
      at reducing the negative impact of mismatch QT intervals on the reproducibility.

PMID- 11844286
TI  - The prognostic accuracy of different QT interval measures.
AB  - BACKGROUND: The QT intervals accuracy for predicting arrhythmic death varies
      between studies, possibly due to differences in the selection of the lead used
      for measurement of the QT interval. The purpose of this study was to analyze the
      prognostic accuracy of all known ways to select the lead. METHODS AND RESULTS:
      Three institutions that used different methods for measuring QT intervals
      provided their QT databases. They included more than 3500 twelve-lead surface
      ECGs. The data represented low- and high-risk patients of the normal population
      (survivors vs dead from cardiovascular causes), acute myocardial infarction
      (survivors versus death from all causes) and remote myocardial infarction (with
      vs without a history of ventricular arrhythmia). The prognostic accuracy was
      defined as the area under the Receiver Operator Curve (ROC-area). The most
      accurate standard leads were I and aVL and the least accurate was AVR. The most
      accurate precordial lead was V4. The prognostic accuracy of the longest QT
      interval was higher than for any standard lead. The prognostic accuracy of the
      mean of the three longest QT intervals was equal to or slightly lower than for
      the longest QT interval. CONCLUSIONS: The highest prognostic accuracy is obtained
      with the longest QT interval. The accuracies of the lead selection methods are so
      different that it can explain a substantial part of the differences between
      otherwise similar studies in the literature. We recommend the use of the mean
      value of the three longest QT intervals.

PMID- 11844287
TI  - Postextrasystolic repolarization abnormalities in ST-U segment in patients with
      ventricular arrhythmias.
AB  - BACKGROUND: Changes in U-wave amplitude after premature ventricular contractions
      (PVC) are known as prognostic markers in the long QT syndrome dependent on
      bradycardia. The purpose of the study was to find correlation between
      postextrasystolic ST-U segment changes and a history of sustained ventricular
      tachycardia or ventricular fibrillation (VT/VF). METHODS: The ST-U segment
      configurations were taken from the 24-hour ambulatory ECG. The comparison of the
      morphology of these segments was performed between sinus beats preceding PVC's
      and first postextrasystolic beats. POPULATION: Two groups of patients were
      evaluated: 1) 32 patients with VT/VF history (VT/VF group), and 2) 36 patients
      with potentially malignant arrhythmia (structural heart disease with frequent
      PVCs and/or nonsustained VT- nsVT) (non-VT/VF group). RESULTS: We found T-wave
      changes in 8 patients (25%) from the VT/VF group and in 12 patients (33.3%) from
      the nonVT/VF group (P = NS) and U-wave changes in 13 patients (40.6%) and 3
      patients (8.3%), respectively (P < 0.05). Other ECG indexes related to PVC's were
      also considered: RR interval, coupling interval (CI), prematurity index (PI), and
      postextrasystolic pause (PP). The analysis of these ECG indices revealed, when
      compared with patients without T-U-wave changes, that the occurrence of U-wave
      changes was significantly related to longer RR interval of the sinus rhythm
      preceding PVC: 1025 +/- 211 vs 918 +/- 200 ms (P < 0.05). The prematurity index
      was lowest in patients with U-wave changes: 0.54 +/- 0.12 vs 0.65 +/- 0.16 (P <
      0.01) while postextrasystolic pauses leading to the postextrasystolic U-wave
      changes were significantly longer: 1383 +/- 223 vs 1130 +/- 247 ms (P < 0.001).
      CI did not differentiate patients: 556 +/- 108 vs 584 +/- 117 ms (P = NS).
      CONCLUSIONS: Postextrasystolic changes in ST-U segment configuration are
      dependent on bradycardia, low prematurity index of the PVC, and the lengthening
      of the postextrasystolic pause. U-wave changes more frequently appeared in
      patients with malignant arrhythmias. Follow-up study is needed to assess if they
      might be predictive for the occurrence or reoccurrence of arrhythmic episodes.

PMID- 11844288
TI  - Holter recordings with continuous marker annotation to evaluate pacemaker
      function.
AB  - BACKGROUND: Pacemaker marker annotations facilitate the interpretation of device
      behavior in addition to ECG recordings. However, they are only available in
      conjunction with a programmer. We studied the diagnostic value of a prototype
      Telemetry Holter Decoder (THD), providing continuous marker annotations on a
      conventional Holter. METHODS: The study included 20 patients with VDD or DDDR
      pacemakers. A 24-hour Holter was performed using the THD. Marker annotations are
      transmitted from the pacemaker to the THD, which transforms them into analog
      signals, which are recorded on one of the Holter channels. RESULTS: During a
      total recording time of 458 hours, high quality marker annotations were retrieved
      for every patient. Artefacts disturbed the recordings during 184 min (0.67%). The
      THD provided information not discernible on the ECG: intermittent atrial
      undersensing during sinus rhythm (1096 times). Atrial tachycardias, not visible
      on the ECG, were detected in 2 patients. The activation of tachycardia response
      algorithms was clearly annotated in 11,516 events. A total of 8875 PVC's
      occurred, 57.8% of which were classified incorrectly in the event counters as
      conducted or fusion beats. Atrial far-field sensing or VA conduction was
      demonstrated 4294 times. Electromagnetic interferences, not visible on the ECG,
      could be seen three times. CONCLUSION: Recording of continuous high-quality
      marker annotation on a conventional Holter is feasible. The THD provides
      important information on device behavior, even in patients assumed to have
      regular device function, and shows to be clearly superior to ECG interpretation
      alone. Such data can be used for improved programming, troubleshooting and for
      the validation of new algorithms.

PMID- 11844289
TI  - Prognostic value of continuous ST-segment monitoring in patients with non-ST
      segment elevation acute coronary syndromes.
AB  - BACKGROUND: Patients with non-ST-segment elevation acute coronary syndromes
      constitute a heterogeneous group concerning prognosis. The 12-lead ECG at rest is
      recommended for early risk stratification but is unable to reflect the dynamic
      nature of myocardial ischemia and coronary thrombosis. This study investigated
      whether continuous ST-segment monitoring provides early prognostic information in
      such patients. METHODS: We prospectively studied 183 patients admitted due to
      chest pain at rest suggestive of an acute coronary syndrome. ST-segment
      monitoring was performed continuously for 24 hours from admission. Cardiac
      specific troponin I levels were determined on admission and every 6 hours for the
      first 24 hours. The endpoint was defined as death or nonfatal myocardial
      infarction, whichever occurred first by 30 days follow-up. RESULTS: ST episodes,
      defined as transient ST deviations of at least 0.1 mV, were detected in 50
      patients (27.3%) and associated with worse 30-day outcome: 22.0% endpoint rate
      compared to 6.8% for patients without ST episodes (P = 0.003). In a multivariate
      analysis, the presence of ST episodes (hazard ratio, 3.07; 95% CI, 1.26 to 7.46;
      P = 0.014) and peak troponin I levels > 0.2 microg/L (hazard ratio, 2.65; 95% CI,
      1.01 to 6.95; P = 0.048) were independent predictors of prognosis. The
      combination of ST-segment monitoring and peak troponin I identified patients at
      low (2.5%, n = 79), intermediate (14.5%, n = 76), and high (25.0%, n = 28) risk
      for the 30-day endpoint. CONCLUSIONS: In patients with non-ST-segment elevation
      acute coronary syndromes, continuous ST-segment monitoring provides on-line early
      prognostic information, in addition to troponin I levels.

PMID- 11844290
TI  - Variable expression of long QT syndrome among gene carriers from families with
      five different HERG mutations.
AB  - OBJECTIVES: This study assessed the phenotypic variability of LQTS in carriers
      with the same and with different mutations in the LQT2 gene. BACKGROUND:
      Mutations of ion-channel genes are known to cause the long QT syndrome (LQTS), a
      disorder associated with distinctive genotypic-specific electrocardiographic
      patterns and variable clinical expression. METHODS: Clinical and
      electrocardiographic characteristics were assessed in five large LQTS families,
      each with a different mutation of the HERG gene (LQT2; n = 469, 69% genotyped,
      102 carriers). One mutation was located on the N-terminus and the other four on
      the C-terminus of the HERG channel protein. RESULTS: The QTc duration and the
      frequency of cardiac events (syncope and LQTS-related cardiac arrest/death) were
      similar among carriers with the five HERG mutations. QTc was as variable in
      carriers of the same mutation as it was among carriers with different HERG
      mutations (P = 0.19). Qualitative assessment of the electrocardiograms revealed
      extensive intra-and interfamilial variability in T-wave morphology. Among
      carriers with multiple electrocardiograms extending over 2 to 7 years, variation
      in QTc over time was minimal. A strong association was found between QTc and the
      occurrence of cardiac events in carriers of all five mutations. CONCLUSIONS: The
      clinical expression of LQTS was equally variable in carriers from families with
      the same or different HERG mutations. These findings highlight the complexity of
      the clinical phenotype in this Mendelian dominant disorder and suggest that one
      or more modifier genes contribute to the variable expression of this syndrome.

PMID- 11844291
TI  - Correction for heart rate is not necessary for QT dispersion in individuals
      without structural heart disease and patients with ventricular tachycardia.
AB  - BACKGROUND: It remains controversial whether QT dispersion should be corrected
      for heart rate, especially when the limitations of rate correction formulae are
      considered. We investigated whether incremental atrial pacing affects QT
      dispersion and the rate-corrected values according to Bazett's formula in
      individuals without structural heart disease and in patients with history of
      sustained ventricular tachycardia. METHODS: We studied 32 individuals without
      structural heart disease (group A), and 16 patients with a history of sustained
      ventricular tachycardia (group B). QT dispersion and corrected for heart rate QT
      dispersion using Bazett's formula (QTc dispersion) were calculated in sinus
      rhythm, and during continuous right atrial pacing for one minute at 100 and 120
      beats/min. RESULTS: Interobserver variability was not significant (P > or =
      0.10). QT dispersion did not differ at rest between groups A and B and did not
      change significantly from baseline at any heart rate in both groups. However, QTc
      dispersion increased significantly with atrial pacing in a similar manner in
      group A and group B (42 +/- 19 ms at rest vs 53 +/- 23 ms at 120 beats/min, P <
      0.001 for group A, 39 +/- 16 ms at rest vs 60 +/- 19 ms at 120 beats/min, P <
      0.001 for group B). CONCLUSIONS: We conclude that QT dispersion remains unchanged
      during atrial pacing at heart rates up to 120 beats/min in both individuals
      without structural heart disease and in patients with a history of sustained
      ventricular tachycardia. Correction by Bazett's formula results in prolongation
      of QTc dispersion, yielding values which may be misleading.

PMID- 11844292
TI  - QT dispersion and viable myocardium in patients with prior myocardial infarction
      and severe left ventricular dysfunction.
AB  - BACKGROUND: QT dispersion (QTd) has been found to correlate to the amount of
      viable myocardium in patients with Q-wave myocardial infarction and well
      preserved LV function. However, this relationship is unknown in patients with
      severe left ventricular dysfunction. METHODS: Thirty-four patients with prior
      large myocardial infarction and severe left ventricular dysfunction underwent Tc
      99m sestamibi single photon emission cardiac tomography (SPECT) and F-18
      fluorodeoxyglucose (FDG) SPECT. Viability was defined as a defect relative count
      density (DCD) of at least 20% greater on FDG SPECT. QTd, corrected QT dispersion
      (QTcd), and QT coefficient of variation (cv) in patients with viable myocardium
      was compared to those without viable myocardium in the infarct area. RESULTS:
      Thirteen patients were excluded from analysis for poor FDG images or inadequate
      ECG tracings. Of the remaining patients, 10 (48%) were found to have viability on
      FDG SPECT. QTd, QTcd, and QTcv in patients with viability were: 58 +/- 22 ms, 61
      +/- 23 ms, and 4.81 +/- 1.76%, respectively, which did not differ significantly
      from those in patients without viability (QTd = 56 +/- 14 ms, QTcd = 70 +/- 16 ms
      and Qtcv = 5.06 +/- 1.20% [P = NS]). Moreover, neither FDG defect size, nor LVEF
      correlated with QTd. CONCLUSIONS: This study indicates no relationship between
      QTd and viability in patients with myocardial infarction and severe left
      ventricular dysfunction.

PMID- 11844293
TI  - Effects of menstrual cycle on cardiac autonomic innervation as assessed by heart
      rate variability.
AB  - OBJECTIVE: The aim of the study was to investigate the effects of menstrual cycle
      on cardiac autonomic function parameters in young healthy women by means of heart
      rate variability (HRV). METHODS: Forty-three nonobese regularly cycling women
      (age 29 +/- 6, range 20-38) were enrolled. Recordings for HRV analysis were
      obtained during the two phases of the menstrual cycle when the estrogen and
      progesterone levels peaked (follicular phase 11 +/- 1 days and luteal phase 21 +/
      1 days from the start of bleeding). Power spectral analysis of HRV was performed
      to calculate the low frequency peak (LF, 0.04-0.15 Hz), high frequency peak (HF,
      0.15-0.40 Hz), LF in normalized unit (LF nU), HF in normalized unit (HF nU), and
      LF/HF ratio during the two phases of menstrual cycle. RESULTS: The heart rates,
      LF and HF, were similar in both phases (P > 0.05). A significant increase was
      noted in the LF NU in the luteal phase compared to follicular phase of the
      menstrual cycle (P = 0.014), whereas a tendency for increased HF NU was observed
      in the follicular phase (P = 0.053). Furthermore, LF/HF ratio was significantly
      higher in the luteal phase compared to follicular phase (2.1 +/- 1.5 vs 1.6 +/-
      0.9, P = 0.002), suggesting increased sympathetic activity in the luteal phase.
      CONCLUSION: We concluded that regulation of autonomic tone is modified during
      menstrual cycle. The alteration in the balance of ovarian hormones might be
      responsible for these changes in the cardiac autonomic innervation.

PMID- 11844294
TI  - Noninvasive diagnosis of cardiac arrhythmias using adenosine compounds.

PMID- 11844296
TI  - Global health assistance: a new perspective.
AB  - Health care priorities for many emerging economies have undergone a dramatic
      transition in the recent past because of the rise in chronic illness, increased
      longevity, and lessened infant mortality. Two additional major societal forces,
      democratization and the information revolution, will alter the nature of global
      health assistance. Because of democratization, governments will feel increasing
      pressure to provide adequate health care. Because of the information revolution,
      all practitioners will know what is available. The convergence of these three
      forces will create an enormous financial burden for emerging economies. Adapting
      to these new realities will be the challenge to donor organizations. What is
      likely to emerge as a critical health care problem around the world is the need
      to balance priorities between acute care and prevention or modification of
      chronic disease. These efforts will be directed at different populations, one
      manifestly ill and one potentially so, and each will need to be recognized
      politically as having valid claims on governmental resources. External support
      will need to include demonstration within the recipient communities that data
      collection permits an accurate identification of disease burden, that risk factor
      modification ameliorates the impact of disease, that continuity of care is
      essential to long term outcomes, and that therapy of developed disease can be
      rationally carried out utilizing evidence based medicine to insure efficiency and
      appropriateness.

PMID- 11844297
TI  - Stokes-Adams disease.

PMID- 11844299
TI  - Surrogacy arrangements in Britain: policy and practice issues for professionals.

PMID- 11844298
TI  - Editorial.

PMID- 11844300
TI  - British Fertility Society survey of all licensed clinics that perform surrogacy
      in the UK.

PMID- 11844301
TI  - Functions and responsibilities of organizations dealing with surrogate motherhood
      in the UK.
AB  - The separation of maternity from social motherhood and progress in reproductive
      technology raise many social, psychological, medical and legal issues (van den
      Akker, 1994). The most recent British Medical Association report (BMA, 1996)
      acknowledged the practice of surrogacy and issued new guidelines for good
      practice and support for those involved. Surrogate motherhood services have
      increased around the country over the last decade, even before the formal British
      Medical Association acknowledgement of their necessity and existence (BMA, 1996).
      The present survey investigated the incidence, accessibility, and functions of
      such organizations, specifically, the legal, medical and psychological problems
      encountered and how they were dealt with, to discover what advice and support is
      given. Ten centres were interviewed. The incidence of surrogacy conducted through
      these organizations is widespread, but the processes involved and therefore the
      implications of the types of surrogacy dealt with are very different. The two
      major surrogacy agencies deal primarily with partial surrogacy, whereas the
      clinics are concerned almost exclusively with full (IVF) surrogacy. Information
      about the procedures involved appears to rely on experience; screening is
      generally carried out 'in house', and psychological factors are dealt with by
      counsellors on request by the couples. In general, although the roles of the
      organizations are disparate and clearly defined, no holistic or long-term care is
      provided by any of the organizations involved with surrogacy in the UK. The
      reasons for this are clear cut and stem from the nature of the organizations, and
      the behaviour of the clients. The data indicate that the current procedures used
      by the organizations are adequate but could be improved and standardized.

PMID- 11844302
TI  - Infertility in Jewish couples, biblical and rabbinic law.
AB  - The Jewish religion is family orientated, and life is guided by 'Halacha', a code
      of conduct based on biblical and rabbinic law. There is a duty to have children,
      in view of the first biblical commandment 'be fruitful and multiply', which
      sanctions most treatments for infertility. Interpretations vary among Orthodox,
      Conservative and Progressive rabbis, but it is only rabbis who have authority to
      advise infertile couples on which procedures concur with Jewish law, and their
      appraisals tend towards leniency in the interests of domestic happiness.
      Prohibitions against 'wasting seed', and against marriage to a man with 'wounded
      testes or severed membrum', may be waived to allow semen collection for analysis
      and treatment for male infertility. All types of assisted conception are
      approved, including in vitro and micro-assisted fertilization, provided the
      gametes are from married couples. In short cycles, artificial insemination can be
      permitted in the post-menstrual week of 'niddah' when coitus is forbidden. Jewish
      descent from the mother is automatic but, for Orthodox couples, a technical
      violation of the law against adultery or incest can spoil the marriage prospects
      of a child or interrupt the paternal priestly line of Cohen or Levi. Donor
      gametes are largely unacceptable to Orthodox rabbis, since egg donation confuses
      the definition of the mother, and because sperm donation creates subterfuge in a
      child's genealogy and a risk of consanguinity. However, Progressive and
      Conservative rabbis place more emphasis on the social attributes of parents and
      frequently approve of gamete donation. The Jewish status of children resulting
      from surrogacy or adoption can be settled by religious conversion. Objections to
      treating unmarried couples, single or lesbian women, and to posthumous
      conception, arise because such households are not traditional families.

PMID- 11844303
TI  - Genetic basis of premature ovarian failure.

PMID- 11844304
TI  - The interface between ethics and clinical practice: principles, procedures and
      personalities.
AB  - Having to say 'no' to patients who are seeking fertility treatment can be
      difficult. Creating new financial or statutory barriers may not resolve the
      ethical problems. Ad hoc legislation may not be able to cope with scientific
      advances, commercial pressures and sympathetic exceptional cases. Political and
      clinical decisions often are made on the grounds of moral pragmatism, 'satisfying
      as many demands as we can' and seeing 'what works'. The best way to make
      pragmatism work for the common good is through education, establishing procedures
      that promote informed public and professional reflection on the issues and ways
      of educating health professionals which value and encourage the growth of
      practical wisdom that is rooted in self-knowledge and imaginative sympathy.

PMID- 11844305
TI  - Philosophical principles in reproductive medicine.

PMID- 11844306
TI  - Gamete and embryo donation: ethical implications for families.
AB  - This paper considers the ethical implications of gamete and embryo donation for
      both donating and receiving families. It suggests that the key ethical issue for
      receiving families is whether to tell the child about the means of conception.
      The ethical debate on this topic gains much from reviewing the research evidence
      of what parents actually do and the reasons they give for their actions. The
      research indicates that very few parents intend to tell the child; however, it is
      noted that this decision needs to be interpreted in the light of the legislation
      in many countries that ensures donor anonymity. It is suggested that the debate
      needs to be extended to include the views of the members of the families of the
      donors (for example, what they consider to be their rights, interests and
      responsibilities in relation to the donor, the donation, the child and the
      receiving families) to achieve an adequate consideration of the ethical
      implications for those families.

PMID- 11844307
TI  - Clinical perspectives on gamete and embryo donation.
AB  - Clinical staff involved in assisted reproduction frequently encounter ethically
      complex clinical problems. Such difficulties often relate to the use of donor
      sperm, eggs or embryos. Despite a fall in the number of donor insemination (DI)
      cycles performed in the UK over the last few years, which is partly explained by
      the availability of intracytoplasmic sperm injection (ICSI), there is still a
      considerable demand for the treatment both in natural cycles and in IVF. The
      burden on clinics in providing sound recruitment and screening strategies for
      donors is enormous and is the subject reviewed in this report. If remuneration of
      donors were withdrawn, as proposed by the Human Fertilisation and Embryology
      Authority (HFEA), the capacity to maintain a clinical service would be in doubt.
      Advances in technology are now pushing to the extremes the limits of what is
      socially acceptable. Those involved in providing clinical services face decisions
      on rationing the limited funds available to treat patients, which in some
      instances may impinge on patient autonomy. Clinical ethics committees may have a
      role in assisting providers in reaching decisions regarding access to treatment.
      Inequity of access to treatment may relate to the inability to pay for treatment,
      with the consequent danger of different ethical standards applying to different
      sectors of the population.

PMID- 11844308
TI  - A team approach to assisted conception treatment.
AB  - A programme to improve 'continuity of care' was initiated at Bourn Hall Clinic in
      direct response to patient demand to see the same doctors and nurses throughout
      assisted conception treatment cycles. A working party comprising individuals from
      all disciplines involved in assisted conception care was set up to review
      practices and aims and to establish an action plan. As a result, in 1996, a team
      approach to in vitro fertilization (IVF) and frozen embryo transfer (FET)
      treatment cycles was introduced at the clinic. The nursing staff were divided
      into two teams, each with a leader, an appropriate skill mix of full- and part
      time nurses, and one full-time and one relief doctor. Treatment cycles were
      scheduled using pituitary downregulation with gonadotrophin-releasing hormone
      (GnRH) agonist when appropriate, and a programme was devised in which groups of
      40--45 couples started treatment during the same 5 day period. Each couple was
      assigned to one of the teams and starting dates for each group were separated by
      2 week intervals. The objectives of the working party were successfully achieved.
      The team approach to treating a finite number of couples provides a better
      opportunity for individualized care. Couples appreciate the advantages of
      continuity of care and the improved rapport with team staff. Forward planning of
      treatment cycles provides greater flexibility for incorporating clinic visits
      into patients' normal routines. Staff have benefited from increased job
      satisfaction due to greater involvement with couples from initial contact to the
      completion of treatment. The new working practice provides opportunities for
      training and research. Staff costs have been rationalized with benefits both to
      couples and to the business unit.

PMID- 11844309
TI  - Genetic counselling issues and male infertility.
AB  - In the past few years, the major genetic causes of male infertility have been
      elucidated and many of these can now be treated using intracytoplasmic sperm
      injection (ICSI). This has raised a number of wider issues in the families of
      people with this type of infertility. Coupled with the essential need for
      individual (or family) confidentiality, this type of treatment demands a very
      careful and sensitive counselling approach. The main requirement is for fertility
      and genetic teams to collaborate to provide a person-oriented approach to the
      application of two very complex and intimidating technologies. An apparent
      difference between established fertility approaches and those of genetic teams
      relates to individual informed choice. The fertility team must address 'the
      welfare of the child' as is encapsulated in the Human Fertilisation and
      Embryology Authority (HFEA) Act of 1990. Since the welfare of the child is a
      subjective matter, decisions are often made by reproductive medicine ethics
      committees in conjunction with fertility teams. This aspect requires further
      development to include the ethos of genetic counselling, which is based more on
      individual informed choice for couples who have been provided with accurate
      information about the impact of a condition on a possible future child. The
      different ethical emphasis is not as great as it might initially appear. Ethics
      committees are now placing much more emphasis on a couple's autonomy in
      individual situations and, correspondingly, genetic centres are providing much
      more information about the possible effects of a couple's decision on the welfare
      of future children.

PMID- 11844311
TI  - Research on reproductive medicine in the pharmaceutical industry.

PMID- 11844310
TI  - Screening of men for sexually transmitted infection and partner notification.

PMID- 11844312
TI  - Y chromosome microdeletions and male infertility.
AB  - Classical cytogenetic mapping has identified a locus on the long arm of the human
      Y chromosome that is required for spermatogenesis and is termed AZF, an acronym
      for the hypothetical azoospermia factor encoded by this locus. Recent molecular
      attempts to identify the gene corresponding to this locus have revealed that
      there are at least three genes in three separate microdeletion intervals. Two of
      these microdeletion intervals contain genes encoding proteins with potential
      roles in RNA metabolism. These genes are members of Y-encoded gene families with
      autosomal homologues. The cell biology of one of these genes, RBM (an acronym of
      RNA binding motif), is complex and suggests a role in pre-mRNA splicing.

PMID- 11844313
TI  - Follicular factors regulating oocyte maturation and quality.
AB  - Maturation of the oocyte can be divided into two different aspects: nuclear
      maturation and cytoplasmic maturation. The spontaneous nature of nuclear
      maturation in oocytes removed from the follicle and cultured in vitro was
      observed in mammals as early as 1935. However, oocytes cultured in basic
      conditions are deficient in some cytoplasmic factors and are, therefore,
      developmentally incompetent. Data from large domestic species indicate that
      although oocytes matured in vitro in supplemented media can develop after
      fertilization, they require the presence of follicular factors during culture to
      ensure their developmental competence. The importance of follicular maturation on
      the capacity of oocytes to achieve fertilization and early embryonic development
      can be studied by reproducing some important events in vitro. Follicular
      supplementation may be in the form of follicular fluid, granulosa cells or
      follicle-conditioned media, and there is evidence that the maturational status of
      the follicle used for co-culture influences subsequent male pronuclear formation.
      Studies in this laboratory on the prolific Chinese Meishan pig, which has
      significantly higher early embryonic survival than conventional European breeds,
      indicate crucial differences in the pattern of follicle development and,
      therefore, the intrafollicular environment in which the oocytes are nurtured. It
      is suggested that this produces oocytes of improved 'quality' and this hypothesis
      is supported by experiments both in vivo and in vitro. Ultimately, it is hoped
      that these studies on large domestic animals will lead to identification of the
      follicular factors that influence oocyte quality.

PMID- 11844315
TI  - Aspects of the less traumatic surgical procedures and some adjuvant therapies in
      prevention of postoperative adhesions.

PMID- 11844314
TI  - Anchorage in the developing placenta: an overlooked determinant of pregnancy
      outcome?
AB  - Anchoring villi are peripheral trophoblastic specializations that attach the
      placenta to the uterine wall. In addition, they supply the migratory trophoblast
      population that colonizes the maternal interstitium and arteries during the first
      18 weeks of pregnancy. Establishment of anchoring villi and subsequent invasion
      of maternal uterine stroma and blood vessels play a critical role in pregnancy
      success; incomplete vascular invasion is associated with common pathological
      conditions of pregnancy, including spontaneous abortion, pre-eclampsia and growth
      retardation. Anchoring villi are already present as early as 18 days after
      ovulation, but new villi develop rapidly as the placenta grows. First trimester
      mesenchymal floating villi, when confronted with a permissive extracellular
      matrix (ECM) in explant culture, undergo de novo development of anchoring sites.
      The cellular and molecular characteristics of these specializations closely
      resemble those that are seen in vivo. It is postulated that development of new
      sites is important in the stabilization of placental attachment during growth and
      development in the first trimester. This may be compromised by function-blocking
      antibodies which inhibit cell--ECM interactions. This is supported by experiments
      in vitro as well as by the presence of auto-antibodies to adhesion molecules in
      women suffering from recurrent spontaneous miscarriage.

PMID- 11844316
TI  - Safe cryopreservation of sperm and embryos.

PMID- 11844317
TI  - Invited commentaries on the Royal College of Obstetricians and Gynaecologists'
      guidelines on the initial investigation of the infertile couple.

PMID- 11844318
TI  - Use of competencies in training fertility nurses in clinical practice.
AB  - In this article, the value of clinical competencies in the role development of
      fertility nurses is discussed using the example of the Oxford Fertility
      Programme. Clinical competencies are incorporated into the training programme
      within the Oxford Fertility Unit to enable new staff to demonstrate their
      clinical ability and undergo assessment while learning new and expanded skills.
      New staff are required to explore both the theoretical and practical foundations
      that underpin clinical practice. Competencies are used in a structured programme
      in which staff have to provide evidence of the appropriate knowledge to perform
      new and expanded procedures. New staff work with a senior nurse, who is their
      lecturer and who assesses both their clinical and theoretical development. The
      new staff are also assigned a preceptor with whom they work on a daily basis to
      consolidate the practice explored with the lecturer. The Scope of Professional
      Practice produced by the United Kingdom Central Council for Nursing, Midwifery
      and Health Visiting (UKCC, 1992) places the emphasis on professional development
      for individual practitioners. Within the Oxford Fertility Unit, the nurses work
      collectively and as autonomous practitioners, which enables them to provide a
      specialized and personal service to their patients. Professional profiles are an
      integral element of an individual's professional development and are used in the
      training programme. They provide an accurate record of a nurse's abilities and
      knowledge and how he or she relates them to practice.

PMID- 11844319
TI  - Evidence-based fertility treatment 1.

PMID- 11844320
TI  - Evidence-based fertility treatment 2.

PMID- 11844321
TI  - Restoring natural function: access to infertility treatment using donated
      gametes.
AB  - Fertility services are the only area of medicine in which health professionals
      are required by law to make social judgements about a person's suitability for
      treatment. The Human Fertilisation and Embryology Act of 1990 imposes
      restrictions on access to licensed fertility treatment based on social judgements
      about the probable welfare of any resulting child. In this paper, it is argued
      that just as social judgements are inappropriate in other contexts, so they are
      in the context of fertility treatment. Furthermore, the ambiguous requirement for
      concern for the welfare of the resulting child simply does not provide a just and
      ethically defensible solution to the problem of access to licensed fertility
      treatment. born as a result of the treatment (including the need of that child
      for a father) and of any other child who may be affected by the birth treatment.

PMID- 11844322
TI  - Ongoing support of the infertile couple -- before, during and after assisted
      conception treatment.

PMID- 11844323
TI  - Prediction of fecundability from semen analysis: problems in providing an
      accurate prognosis.
AB  - Information from semen analysis is used to predict the likelihood that a couple
      will conceive within a period of time. It is only possible to provide a
      probability; there can be no certainty. The probability is influenced by a host
      of factors including semen quality, and studies in large groups or using simple
      models are required to overcome this. Delayed conception from natural intercourse
      or poor fertilization at IVF has limited predictive power for a subsequent
      attempt. The problem is made worse by variations in sperm parameters among
      different ejaculates from the same man and by differences among groups of
      patients. Results of studies of potential criteria should be presented in a way
      that allows the effect of the test result on the probability of conception to be
      appreciated, and results should be confirmed on independent data sets. When there
      is potential for fertility, estimation of fecundability can only be approximate;
      however, progress is possible. Effects of semen quality can be clearly identified
      in large groups, and computer assisted semen analysis measurements do provide
      useful additional information for the success of intracervical insemination.

PMID- 11844324
TI  - A critical look at semen analysis.
AB  - In this article, human semen analysis is examined critically and some of the
      difficulties it presents in terms of interpretation are highlighted. The problem
      of defining fertility is raised and a brief comparison is made between farm
      animals and humans. The purpose of analysis in each differs markedly, yet
      conventional tests on human semen are derived from semen analysis in animals.
      Sperm count, sperm motility and sperm morphology are considered and the point is
      made that in attempts to predict the fertilizing capacity of a semen sample,
      measurement of the volume of the semen is unhelpful. It is also stressed that
      several different tests must be applied for a meaningful report to be produced.
      It is suggested that different boundaries from those applied in animals are
      required in humans. This is because there is much greater variation in the
      quality of human semen than in that of animals and, therefore, in trying to
      establish a norm, a broader framework is required. Finally, it is proposed that
      fundamental research into the physiology of human spermatozoa is necessary to
      achieve better standards in semen testing in the future.

PMID- 11844325
TI  - Non-functional fertility genes in humans: contributory factors in reduced male
      fertility?
AB  - Many of the mammalian sperm surface proteins that have been characterized in
      recent years have been implicated in sperm--egg interactions and subsequent
      fertilization. In particular, several members of the MDC protein family, most
      notably fertilin alpha, fertilin beta and cyritestin (also known as tMDC I), play
      an important role in sperm--egg interactions in rodents. In light of current
      data, it is proposed that many of these sperm proteins act co-operatively, and
      that the concerted effects of several proteins leads to 'maximum fertilizing
      ability', but that individual proteins are functionally redundant and are
      therefore not essential. Nevertheless, the co-operative nature of these
      interactions means that loss of individual proteins might lead to a concomitant
      reduction in fertilizing ability, a proposal that is supported by our recent
      finding of non-functional fertilin alpha and tMDC I genes in humans.

PMID- 11844326
TI  - Receptors and channels regulating acrosome reactions.
AB  - Prospective clinical studies informed by cloning and sequencing of sperm surface
      receptors and metal ion channels have elucidated critical early steps in the
      acrosome reaction that explain aspects of metal ion-related male infertility.
      Induction of the acrosome reaction is proposed to include non-nuclear
      progesterone receptor activation of Shaker-related sperm head voltage-gated
      potassium ion channels (VGKC). Men express VGKC isoforms with differing
      sensitivities to lead (Pb(2+)) inhibition, thus explaining interindividual
      variabilities in Pb(2+)-related male infertility. VGKC opening induces calcium
      (Ca(2+)) transients, and a signalling cascade induced by zona receptor
      aggregation requires an actin cytoskeleton created by the VGKC-induced Ca(2+)
      transients. Actin polymerization and stabilization, favoured by zinc (Zn(2+)) and
      depolymerized by cadmium (Cd(2+)), may mediate low Zn(2+) and high Cd(2+)
      infertile states. Zona receptor aggregation induces phosphotyrosine signals at
      sites, including sperm voltage-dependent Ca(2+) channels (VDCC), intermediate in
      electrophysiology between T- and L-type channels. Sperm surface VDCC localize at
      the sperm equatorial segment, the terminus of zona receptor translocation.
      Opening of VDCC admits a second Ca(2+) wave that activates phospholipase C
      phosphorylated in the zona receptor cascade. Phospholipase C induces fusogenic
      lipids and activates actin-severing proteins, depolymerizing the actin
      cytoskeleton and permitting apposition and fusion of acrosomal and plasma
      membranes.

PMID- 11844327
TI  - Functional aspects of mammalian sperm chromatin.
AB  - During spermiogenesis, the histones in the round spermatid, which bind the DNA in
      a relatively open configuration leaving much of the DNA exposed, are replaced by
      the much more tightly binding protamines, which package the DNA into highly
      condensed toroids. This knowledge has led to models of sperm chromatin structure
      that characterize the DNA as highly condensed and biologically inert, a view that
      is substantiated by the lack of detectable mRNA transcription or DNA replication
      in mature sperm nuclei. However, this view of sperm chromatin structure has been
      challenged recently by new data from several laboratories, including our own.
      These data indicate that mammalian sperm nuclei can interact with exogenous DNA
      and undergo sperm-specific apoptosis. We propose a model for sperm chromatin
      structure that provides a mechanism by which the tightly compacted mammalian
      sperm chromatin may be capable of these activities.

PMID- 11844328
TI  - Ca(2+) oscillations and sperm factors at fertilization in mammals.
AB  - At fertilization in mammals, the spermatozoon triggers a series of Ca(2+)
      oscillations that are essential for activating the oocyte. The reason why the
      spermatozoon triggers Ca(2+) oscillations, as opposed to a single Ca(2+)
      increase, is unknown. However, there is evidence that more than one Ca(2+)
      increase is required for efficient rates of pronuclear formation. In addition,
      the pattern of Ca(2+) oscillations may affect later development. It is not known
      how the spermatozoon triggers Ca(2+) release in the oocyte, but it may act by
      introducing a cytosolic factor after gamete membrane fusion has taken place. This
      factor is characterized by its ability to cause Ca(2+) oscillations and is
      referred to as an oscillogen. The protein components that make up the sperm
      oscillogen remain unclear.

PMID- 11844329
TI  - Successful transvaginal ultrasound-guided ablation of a cervical pregnancy in a
      patient with simultaneous intrauterine pregnancy after in vitro fertilization and
      embryo transfer.
AB  - Heterotopic pregnancy, or simultaneous intrauterine and extrauterine gestation,
      is a relatively rare condition. However, induced ovulation and assisted
      reproductive technologies have markedly increased the incidence of this
      condition. In this article, a case of heterotopic pregnancy after in vitro
      fertilization and embryo transfer is presented in which the viable cervical
      pregnancy was treated by transvaginal ultrasound-guided puncture and injection of
      potassium chloride in conjunction with methotrexate at week 6 of gestation. At
      week 12 of gestation, the intrauterine gestation was viable and complete
      resorption of the cervical pregnancy had occurred. At week 30 of gestation, a
      healthy baby was delivered by Caesarian section after prelabour rupture of
      membranes.

PMID- 11844330
TI  - Plasma prolactin measurement is not indicated in women in the routine
      investigation of uncomplicated infertility.
AB  - Measurement of plasma prolactin frequently forms part of the routine
      investigation of infertile couples. In 315 consecutive women attending an
      infertility clinic in a university teaching hospital, all of those with increased
      plasma prolactin concentrations would have been detected from their symptoms. All
      women with prolactin concentrations in the range 500--800 miu l(minus sign1)
      appeared to be ovulating. These data support previous proposals in guidelines
      published by both the European Society for Human Reproduction and Embryology
      (ESHRE, 1996) and the Royal College of Obstetricians and Gynaecologists (RCOG,
      1998) that there is no benefit in measuring plasma prolactin in the investigation
      of infertility in women who are menstruating normally and have no other clinical
      indications.

PMID- 11844332
TI  - Evidence-based reproductive medicine.

PMID- 11844331
TI  - Meeting report: Association of Clinical Embryologists.

PMID- 11844333
TI  - Royal College of Nursing (RCN) Fertility Nursing Conference 1999.

PMID- 11844335
TI  - Short- and long-term risks for women having IVF -- what is the evidence?

PMID- 11844336
TI  - Gonadal tissue cryopreservation: clinical objectives and practical prospects.

PMID- 11844334
TI  - Gamete donation: ethical implications for donors.
AB  - The interests of gamete donors have only recently been recognized in assisted
      reproduction; traditionally, the interests of the patients (typically a couple)
      and the prospective child are paramount. However, assisted reproduction would not
      be possible without donors, and the simple utilitarian view would be to place
      their interests first to maximize the availability of the practice. There are
      several ethical issues on both sides of the donor--recipient equation, some of
      which are mutual and others are in conflict. For example, the word 'donation'
      implies there is no payment. Informed consent for donation is essential if the
      autonomy of the donor is to be respected, and includes information about the
      results of screening. This is a sensitive issue, especially when pathology is
      found in a donor who is not being screened for his or her own immediate benefit.
      Counselling may result in donors refusing to take part, but may also lead to
      selection by the person recruiting the donors, sometimes as a consequence of
      examining the motivation of the donor. In this case, the main problem is the
      ethical basis of the selection process. Other aspects of gamete donation may lead
      to a conflict of interests between the donor, the recipients and even the
      prospective child, particularly in terms of anonymity and the information that is
      made available about the specific circumstances of donation. Implications and
      support counselling are essential tools in achieving an acceptable balance for
      all parties involved.

PMID- 11844337
TI  - Ethical dilemmas arising from the cryopreservation of gametes.

PMID- 11844338
TI  - Aims of the HFEA: past and future.
AB  - Public reaction to breakthroughs in fertility treatment and embryo research tends
      to be extremely mixed, revealing an often ambivalent attitude to science itself.
      After 12 years of intense public debate about the ethics of IVF and human embryo
      research, Parliament passed the Human Fertilisation and Embryology Act 1990,
      which established the Human Fertilisation and Embryology Authority (HFEA). The
      aims of the HFEA are to regulate licensed clinics in a rigorous but sensitive
      way; to protect patients who may be vulnerable to exploitation, whether intended
      or inadvertent; to enable this sensitive area of science and medicine to progress
      in a responsible way; and to reassure the public that the possible excesses are
      guarded against. The HFEA is an arbiter over several balancing acts: especially
      the balance between the practitioner's right to clinical freedom and scientific
      progress against protection of patients, future offspring and the limits of
      public acceptability; or the right of access to treatment against the need to
      maintain acceptability, respectability and safety. In the last 8 years several
      issues have arisen that challenge society's view of what is 'normal' or
      'acceptable' in human reproduction, and this will undoubtedly continue to happen
      in the future. These issues have been difficult for society to accommodate, and
      have presented serious challenges to conventional ideas. However, the HFEA has
      been able to assure both public and legislators that clinics are acting
      reasonably and that there are adequate controls in place.

PMID- 11844339
TI  - Time waits for no one': IVF patients' evaluations of their experiences of the
      National Health Service waiting list.
AB  - This study investigated patients' evaluations of the costs and benefits of in
      vitro fertilization funded by the National Health Service, which is characterized
      by long waiting lists, a restricted number of treatment cycles and reduced
      chances of success. This paper reports the waiting list data. This was a
      prospective in-depth cohort study of 21 couples from one clinic, plus a
      comparison group of 99 couples, to establish the representativeness of the cohort
      couples. The cohort couples were interviewed three times: (i) before the start of
      treatment, (ii) after the first cycle of treatment and (iii) at the end of
      treatment. A total of 80% of the cohort couples had waited more than 3 years for
      treatment. Important themes raised in the interviews include: patients'
      understanding of what it means to be on the waiting list; their predicted versus
      actual waiting time; how they managed their time on the list; their reactions to
      coming off the list; and their views on how the list could be improved. Overall,
      patients thought their treatment had been worthwhile but that the time spent
      waiting for treatment was too long and was puzzling. It is concluded that the
      waiting list involves hidden costs for patients, clinics and the National Health
      Service.

PMID- 11844341
TI  - Pathogenic mitochondrial DNA mutations and human reproduction.

PMID- 11844340
TI  - Difference in mRNA expression and occurrence of plasminogen activator inhibitors
      in intrauterine decidua of normal and ectopic human pregnancies.
AB  - The objective of this study was to elucidate the mechanisms involved in the
      formation of a functional decidua. The concentrations of plasminogen activators
      and plasminogen activator inhibitors in intrauterine decidua from normal and
      ectopic pregnancies were compared. Intrauterine decidua was obtained by curettage
      from 17 women with ectopic pregnancies and from five women with normal
      pregnancies. The gestational age was similar in the two groups. The antigen
      concentrations of plasminogen activators and plasminogen activator inhibitors in
      decidua homogenate were determined by ELISA and fibrinolytic activity was
      measured on fibrin plates. Localization was determined by immunohistochemical
      staining and mRNA was identified by in situ hybridization. Fibrinolytic activity
      was absent in decidua from normal pregnancies but present in the intrauterine
      decidua from ectopic pregnancies. High antigen concentrations of the inhibitors
      of fibrinolysis, PAI-1 and PAI-2, were found in normal decidua in contrast to low
      concentrations in decidua from ectopic pregnancies. Staining for PAI-1 as well as
      PAI-2 was positive in decidual cells. In situ hybridization resulted in high
      intensity signals for PAI-1 as well as for PAI-2 mRNA in decidua from normal
      pregnancies in contrast to very low intensity signals in decidua from ectopic
      pregnancies. The absence of proteolytic activity and high expression of PAI-1 and
      PAI-2 in normal decidua might facilitate attachment of the fertilized ovum and
      might also prevent detachment of the decidua.

PMID- 11844342
TI  - Local regulation of spermatogenesis: a living cell approach.
AB  - The normal function of the testis is dependent on stimulation by pituitary
      gonadotrophins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH).
      Targets for these hormones are Leydig cells in the interstitial tissue, and
      Sertoli cells in the seminiferous epithelium, respectively. The effect of LH on
      the seminiferous epithelium is mediated by testosterone produced by the Leydig
      cells. Therefore, the two main hormones that influence the function of the
      seminiferous epithelium directly are FSH and testosterone. The preferential
      action of FSH in the adult seminiferous epithelium is associated with stages that
      involve meiotic divisions and early spermiogenesis. The parameters related to
      androgen action predominate at different stages during which the final maturation
      of the spermatids, spermiation and the onset of meiosis take place. The stage
      dependent variation of the hormone responses in the seminiferous epithelium
      indicates the presence of local paracrine regulation and cell interaction
      mechanisms in the seminiferous epithelium, which are dependent on the
      spermatogenic cells associated with the Sertoli cells. Several growth factors
      have been suggested as mediators of this interaction. Owing to its highly complex
      structure, the seminiferous epithelium has been a difficult area for biochemical
      studies. New in vitro techniques have made these studies possible, and particular
      advances have been made using recombinant DNA techniques and transgene
      technology.

PMID- 11844343
TI  - Germ cell transplantation in the male: animal studies with a human perspective.
AB  - Germ cell transplantation has been developed in rodent models. The transfer of
      donor germ cells into the seminiferous tubules of mice leads to re-initiation of
      donor spermatogenesis in the host testis and restoration of fertility.
      Furthermore, cryopreservation of donor cells or culture of germ cells before the
      transfer is feasible. Xenologous transfer of rat and hamster germ cells results
      in the production of foreign gametes in the mouse testis. From a clinical
      perspective, this methodology has the potential to restore fertility in patients
      whose testes have been damaged due to oncological therapy. This review summarizes
      the existing data on animal models and introduces the first preclinical attempts
      for preserving germ cells in patients undergoing oncological treatment. As
      improved therapeutic regimens have markedly increased the life expectancy of
      oncological patients, it seems timely to develop improved strategies for
      restoring the maximum quality of life after recovery from the disease. The loss
      of fertility is one of the most problematic negative side effects in young male
      oncological patients. Germ cell transplantation offers the potential for
      protection of the male germ line during gonadotoxic therapy and restoration of
      fertility.

PMID- 11844344
TI  - Pharmacological adjuvants during infertility surgery: a systematic review of
      evidence derived from randomized controlled trials.
AB  - The aim of this study was to evaluate systematically the role of pharmacological
      agents used as adjuvants during infertility surgery to prevent or reduce
      postoperative adhesion formation and improve pregnancy rates. Meta-analyses were
      performed of the ten randomized controlled trials identified that evaluated the
      use of pharmacological adjuvants at infertility surgery. The administration of
      steroids, dextran 70, noxytioline, heparin, or promethazine have all been
      investigated for their adjuvant role in preventing adhesion formation during
      pelvic surgery for infertility. Outcome measures were taken as: pregnancy rates
      after infertility surgery; number of patients with absent, improved or
      deteriorated adhesions at second look laparoscopy (dichotomous outcomes); and
      changes in adhesion score from initial surgery to second look laparoscopy
      (ordinal outcome). None of the pharmacological adjuncts investigated in a
      randomized controlled fashion was shown to improve postoperative pregnancy rates.
      There was some evidence that steroids reduced the incidence or severity of
      postoperative adhesion formation; there was little evidence to support the use of
      dextran. The routine use of pharmacological adjuncts during infertility surgery
      cannot be recommended on the basis of the available evidence derived from
      randomized controlled trials. Dextran appears to offer no advantage. The evidence
      with regard to steroids is far from conclusive but tentatively indicates that
      they may be beneficial.

PMID- 11844346
TI  - Obituary: Professor Michael Hull.

PMID- 11844345
TI  - Editorial.

PMID- 11844347
TI  - BFS Recommendations for Good Practice on the Storage of Ovarian and Prepubertal
      Testicular Tissue.

PMID- 11844348
TI  - Electronic transfer of mandatory infertility information: survey of opinion of
      licensed treatment centres.

PMID- 11844349
TI  - Families from assisted conception: ethical and psychological issues.
AB  - This article gives the findings of an in-depth study of the outcome for parents
      and children after assisted conception, namely in vitro fertilization and donor
      insemination. The study is of 54 families bringing up 110 children, 74 of whom
      were the result of these two medical interventions. The findings presented in
      this article deal specifically with the psychological issues and ethical dilemmas
      experienced by the parents of these two groups. Specific areas regarding in vitro
      fertilization are use of the term 'test-tube baby'; religious and community
      attitudes to the use of assisted reproductive technology; and the effects of
      these attitudes on the families. The major issue of multiple births and their
      social outcomes is dealt with in the following article. The specific areas for
      donor insemination families are secrecy and reticence about the whole procedure;
      infertility as a continuing taboo subject; donor anonymity; and the resulting
      effect of donor anonymity on parenting children who do not have access to their
      full health and genetic family history. Reference is made to the findings of
      other relevant research. Practice and legal implications from the findings are
      presented.

PMID- 11844350
TI  - Euphoria or despair? Coping with multiple births from ART: what patients don't
      tell the clinics.
AB  - Patients' perception of family life after a multiple birth: euphoria or Pandora's
      box? The aim of this article is to explore the realities of parenting children
      from a multiple pregnancy as an aid to decision-making about the number of
      embryos transferred. Outcome research regarding parenting of children from twin,
      triplet and higher order births is described and, in particular, children of
      multiple births from assisted reproductive technology. Current understanding of
      interpersonal relationships in multiple birth families is also discussed. The
      evidence from these various sources is put in the framework of social risk
      factors as an aid to predicting outcomes and as an essential part of decision
      making with the full participation of patients. The implications of such an
      approach is presented in relation to support for such families. Case studies are
      included of three triplet families. Reference is made to fetal reduction as an
      option.

PMID- 11844351
TI  - Possible consequences of performing intracytoplasmic sperm injection (ICSI) with
      sperm possessing nuclear DNA damage.
AB  - A number of studies have confirmed that sperm with damaged nuclear DNA are
      present in human ejaculate. It appears that these sperm are more likely to occur
      in men with low concentrations of sperm, or poor sperm motility or morphology. In
      assisted reproductive techniques, in particular intracytoplasmic sperm injection
      (ICSI), there is a higher statistical chance that sperm possessing damaged DNA
      will be selected and used to fertilize oocytes. In light of this observation, the
      question of whether human sperm with damaged DNA can impair fertilization and
      embryo development is examined.

PMID- 11844352
TI  - Intracytoplasmic sperm injection (ICSI): risks reconsidered.
AB  - The aim of this article is to address some of the questions raised by the
      introduction of new techniques to alleviate infertility, using intracytoplasmic
      sperm injection (ICSI) as an example. Although any new technique has the
      potential to cause unanticipated harm and it is probably true that no treatment
      is risk-free, current practice demands that risks are, as far as possible,
      minimized during trials and when offered as treatment. It is expected that those
      taking part in trials, possibly even more than patients, should be given
      information on potential hazards so that they may choose whether to participate.
      However, particular problems arise when dealing with techniques to assist
      reproduction, since there may be risks not only to the recipients of treatment
      but also to the children who may result from the treatment. Therefore, risks to
      the children, as much as to the parents, deserve consideration and these
      potential subjects of risk will be the focus of this article. The different types
      of risk will be considered and the issue of whether children can be regarded as
      being harmed as a result of being conceived by such procedures will also be
      explored.

PMID- 11844353
TI  - Apoptosis in mammalian preimplantation embryos: regulation by survival factors.
AB  - The formation of a developmentally competent mammalian blastocyst requires the
      transition from a unicellular state, the fertilized zygote, to a differentiated
      multicellular structure. In common with other developing organisms, generation of
      the required cell population involves the processes of cell division,
      differentiation and cell death, all of which can be regulated by peptide growth
      factors. Cell death in the preimplantation embryo occurs by apoptosis and, by
      analogy with other systems, may serve to eliminate unwanted cells during the
      critical developmental transitions that take place during this period. Cells may
      be eliminated because they are abnormal or possess defects, including damaged DNA
      or chromosomal abnormalities. At the early cleavage stages, apoptosis may be
      associated with activation of the embryonic genome and may contribute to the
      blastomere fragmentation commonly observed in human IVF embryos. The major wave
      of apoptosis occurs in a number of species in the inner cell mass of the
      blastocyst, as identified using nuclear labelling including terminal transferase
      mediated dUTP nick end labelling (TUNEL) and fluorescence and confocal
      microscopy. Apoptosis may protect the integrity and cellular composition of the
      inner cell mass, by eliminating damaged cells or possibly those with an
      inappropriate phenotype. Preimplantation embryos express genes involved in the
      regulation and execution of apoptosis and their cells can undergo this default
      pathway in the absence of exogenous survival signals. Evidence is now
      accumulating from several species that apoptosis in the embryo is regulated by
      soluble peptide growth factors acting as survival factors in an autocrine or
      paracrine manner. To date, these include transforming growth factor alpha and
      members of the insulin-like growth factor family. Apoptosis may also be affected
      by environmental factors, including culture conditions and the composition of
      media. The regulation of apoptosis in the preimplantation embryo is likely to be
      of critical importance for both embryo viability and for later development, since
      the cells of the inner cell mass give rise to the fetus and carry the germ line.

PMID- 11844354
TI  - Molecular approaches to the study of gene expression during human preimplantation
      development.
AB  - Understanding of gene expression during the early stages of human development has
      increased markedly in the last 2 years, as refined and highly sensitive
      procedures have been developed enabling construction of cDNA libraries from
      single preimplantation embryos and unfertilized oocytes. The genes identified so
      far include key regulatory genes such as imprinted genes, transcription factors
      and cell cycling genes, as well as repetitive sequences, brain transcripts and
      housekeeping genes. In addition, sequencing of random clones has revealed cDNAs
      matching known expressed sequence tags in the GenBank and dbEST databases, in
      addition to novel sequences not currently present in these databases. This
      article focuses on the various molecular biology techniques applicable to the
      study of gene expression during human preimplantation development.

PMID- 11844355
TI  - Obstetric outcome and follow-up of children born after in vitro fertilization
      (IVF).
AB  - In vitro fertilization (IVF) is a well established and effective method for the
      treatment of infertility, but there is concern about the health of children born
      as a result of this procedure. The introduction of new technologies, such as
      intracytoplasmic sperm injection (ICSI), has increased concern that the offspring
      from such techniques may be at increased risk, particularly of malformations.
      Studies on obstetric and neonatal outcome and early infant development after IVF
      obtained from a Medline search were reviewed. Children born after IVF had a
      considerably higher risk of being born pre-term and with a lower birth weight
      than children conceived naturally. A high incidence of multiple births and
      maternal characteristics were the main factors responsible for the increase in
      adverse outcome. Novel strategies in assisted reproduction, including the
      development of single embryo transfer regimens and avoidance of multiple births,
      are required. There is also a need for further developmental follow-up of
      children born after assisted conception, especially those born after ICSI.

PMID- 11844356
TI  - Insulin sensitivity and fertility.
AB  - This review sets in context significant recent advances in the understanding of
      the pathophysiology of polycystic ovary syndrome (PCOS). The occurrence of
      variable insulin sensitivity in individuals is discussed. Information is
      presented to demonstrate that prolonged anovulation decreases insulin sensitivity
      and, conversely, that improvement in insulin sensitivity normalizes ovarian
      function in PCOS. In addition, a meta-analysis of studies on metformin and
      troglitazone treatment in PCOS is presented.

PMID- 11844357
TI  - Definition of polycystic ovary syndrome.
AB  - This article aims to answer two questions in defining polycystic ovary syndrome
      (PCOS): what is PCOS and how should the syndrome be recognized in clinical
      practice? Whether PCOS is a primary or a secondary ovarian disease remains
      controversial. It has been suggested for many years that the main
      pathophysiological factor in PCOS is dysregulation of the relationship between
      the hypothalamus, the pituitary and the ovary. However, PCOS also involves
      intraovarian morphological and functional abnormalities. With respect to clinical
      practice, many reports have questioned the sensitivity as well as the specificity
      of a high LH concentration. Similarly, the biological hyperandrogenism of PCOS
      cannot define the syndrome. GnRH agonist or hCG tests are not convenient for the
      diagnosis of PCOS in practice. Stromal hyperplasia is considered to be indicative
      of PCOS but it is highly dependent on the settings of the ultrasound machine,
      thus use of the total ovarian area, the upper normal limit of which is 5.5 cm(2),
      is recommended. The need for diagnostic markers of PCOS depends on the clinical
      presentation. In the full-blown syndrome (classic PCOS), the clinical symptoms
      provide the most powerful indication and the association of the three components
      (hyperandrogenism, anovulatory dysfunction and metabolic abnormalities) has a
      strong diagnostic potency. In non-classic PCOS, a cost-effective and safe work-up
      should be applied, which includes ultrasonography and hormonal assays (basal
      serum concentrations of testosterone, sex hormone binding globulin, 17
      hydroxyprogesterone, LH, FSH and prolactin). Asymptomatic PCOS may be discovered
      incidentally during ultrasonography, and it is important to take this finding
      into account when designing an ovulation induction protocol. In most cases of
      PCOS, the diagnosis may remain presumptive providing other diagnoses have been
      ruled out and the follow-up does not disclose any atypical development of the
      condition.

PMID- 11844358
TI  - Pathogenesis of polycystic ovary syndrome: evidence for a genetically determined
      disorder of ovarian androgen production.
AB  - Polycystic ovary syndrome (PCOS) is the commonest endocrine disorder in women of
      reproductive age. It is the major cause of anovulatory infertility and of
      hirsutism but its aetiology remains uncertain. The most consistent biochemical
      abnormality is hypersecretion of androgens. In this review, evidence is presented
      to support the view that a genetically determined abnormality of ovarian androgen
      secretion is the primary cause of the syndrome. Molecular genetic studies have
      demonstrated that CYP11a, the gene encoding P450 cholesterol side chain cleavage,
      is a major susceptibility locus for development of hyperandrogenism in PCOS.

PMID- 11844359
TI  - Function of the polycystic ovary.
AB  - The mechanism of the increase in the number of follicles in polycystic ovaries
      (PCO) is still not understood, but most data indicate that folliculogenesis is
      abnormal at all stages. This increase is probably due to prolonged follicle
      growth in both ovulatory (ov) and anovulatory PCO (anovPCO) rather than over
      recruitment from the primordial stage. There appear to be fewer follicles in
      ovPCO than in anovPCO and this may be due to slow growth combined with arrested
      development in the anovPCO, preventing the normal process of atresia. This idea
      is supported by data indicating that the preponderance of structures in anovPCO
      are functional follicles rather than atretic cysts. In contrast, follicles in
      ovPCO are primarily atretic, analogous to the situation in the normal ovary.
      Closer analysis of the function of these follicles reveals an intrinsic defect in
      the theca cell layer in the expression of the genes encoding steroidogenic
      enzymes. Although androgen production is increased in all PCOs, the serum
      concentrations of androgen tended to be higher in anovulatory women indicating
      that there may be a link between the ovarian concentration and anovulation.
      Granulosa cells in small follicles from anovPCO behave in a similar fashion to
      those in preovulatory follicles from normal ovaries in terms of steroidogenic
      responses. This, in combination with the finding of LH-responsiveness in small
      follicles from anovPCO, has led to the suggestion that these follicles are
      prematurely luteinized. The recent finding that follistatin gene regulation may
      be abnormal in women with polycystic ovary syndrome (PCOS) provides a new insight
      into the possible defect in the function of these ovaries. Elucidation of the
      precise nature of the defect may provide the key to understanding the apparent
      contradiction of increased steroidogenesis in the presence of abnormal and
      arrested follicle growth.

PMID- 11844360
TI  - The role of inhibin in polycystic ovary syndrome.
AB  - Polycystic ovary syndrome (PCOS) is a common heterogeneous disorder which, in its
      severest manifestations, is associated with anovulation, hyperandrogenism and
      metabolic imbalance. The biochemical markers for the condition can include a
      significantly raised LH:FSH ratio and a raised testosterone concentration,
      indicating a derangement of the hypothalamo--pituitary--ovarian axis which may be
      primary or secondary to a primary ovarian pathology. The bioactive inhibins are
      heterodimeric glycoproteins consisting of alpha-betaA (inhibin A) and alpha-betaB
      (inhibin B) subunits. They play an endocrine role in co-regulating (with
      oestradiol) the suppression of FSH during the late follicular and luteal phases
      of the ovarian cycle and they are implicated in intraovarian paracrine
      signalling. Inhibin B, which is the predominant form in small pre-ovulatory
      follicles, increases in concentration from early in the follicular phase to reach
      a peak coincident with the onset of the decrease in FSH which forms the basis of
      the pattern of mono-ovulation seen in normo-ovulatory women. Several unique
      features of the dysovulation of women with PCOS, namely their failure to recruit
      and develop a dominant follicle despite having 'normal' concentrations of
      endogenous FHS, the raised LH:FSH ratio and their exquisite sensitivity to
      exogenous FSH injections, may be explained by their significantly higher inhibin
      B concentrations. Studies into inhibin B parameters in women with PCOS
      demonstrate that women with anovular PCOS have significantly higher
      concentrations of circulating inhibin B and that they lack the pulsatile pattern
      of secretion that can be detected in normo-ovulatory women during the mid
      follicular phase. The inhibin B response to ovulation induction with clomiphene
      citrate in women with PCOS differs from that in normo-ovulatory women taking the
      antioestrogen. Women with PCOS who over-respond to ovulation induction with
      injected FSH in a 'low-dose' step-up protocol' and recruit multiple follicles
      have significantly higher concentrations of pre-treatment inhibin B than PCOS
      subjects who do not.

PMID- 11844361
TI  - Hyperinsulinaemia and polycystic ovary syndrome.
AB  - Over the past 20 years, it has been established that hyperinsulinaemia is a
      fundamental disturbance in many women with polycystic ovary syndrome (PCOS). A
      subgroup of women with this syndrome have 'metabolic PCOS' which can be
      considered to be a pre-diabetic state. Clinically, this subgroup is most easily
      identified in obese women with a strong family history of diabetes in whom
      menstrual disturbance is the predominant feature. There is an urgent need to
      define the more subtle features in young lean women with PCOS, in whom the
      metabolic syndrome is yet to emerge, which would enable the prediction of future
      health risks. The molecular mechanisms of insulin resistance leading to
      hyperinsulinaemia are now being elucidated. Abnormalities of both insulin
      secretion and intracellular insulin signalling have both been proposed in women
      with PCOS. Strategies to lower serum insulin concentrations include diet,
      exercise and possibly, oral insulin sensitizing agents such as metformin.
      Although the short-term efficacy of reducing hyperinsulinaemia in women with PCOS
      is clear, the best method to prevent the progression to diabetes later in life
      has not been defined.

PMID- 11844362
TI  - Polycystic ovary syndrome in adolescence and early adulthood.
AB  - Polycystic ovaries and the associated syndrome are recognized as the most common
      cause of endocrine disturbances in adult women, but much less research has been
      performed to examine how polycystic ovary syndrome (PCOS) presents in girls and
      young women. Polycystic ovaries have been demonstrated in childhood, and there is
      evidence to show that even very young women may show symptoms and signs of the
      associated syndrome. Closer examination of younger populations (less-than-or-eq,
      slant 25 years of age), and in particular, studies of girls during the transition
      from puberty into early adulthood (adolescence), may provide new insights into
      the pathogenesis and natural history of polycystic ovaries and PCOS, and may
      indicate whether polycystic ovaries could potentially be considered as a marker
      for health screening. Consideration should be given to the management of girls
      and young women with polycystic ovaries and PCOS as this group may have different
      needs and health risks compared with older women.

PMID- 11844363
TI  - Long-term consequences of polycystic ovary syndrome: results of a 31 year follow
      up study.
AB  - A cohort of 786 women who received a diagnosis of polycystic ovary syndrome
      (PCOS) in the United Kingdom before 1979 was traced to investigate the long-term
      consequences of the syndrome. Data were obtained from death certificates for 70
      women. Morbidity data were collected from general practice records and
      questionnaires for 319 women diagnosed with PCOS an average of 31 years
      previously and for 1060 age-matched control women. The proportion of women with
      involuntary infertility was 17.5% in the PCOS group compared with 1.3% in the
      control group. All-cause mortality in the cohort did not differ from that of the
      general population of women. Women with PCOS were not at significantly increased
      risk of mortality or morbidity from breast cancer but were at increased risk of
      endometrial cancer. Women with a history of PCOS had higher levels of several
      cardiovascular risk factors including diabetes, hypertension, raised plasma
      cholesterol and body mass index > 30 kg m(minus sign2). Mortality and morbidity
      from coronary heart disease did not differ significantly between the women with
      PCOS and comparison groups. Control of obesity is likely to be particularly
      important for women with a history of PCOS.

PMID- 11844364
TI  - Ovulation induction for polycystic ovary syndrome.
AB  - Polycystic ovary syndrome (PCOS) is the commonest cause of anovulatory
      infertility. Various factors influence ovarian function, and fertility is
      adversely affected by an individual being overweight or having high serum
      concentrations of LH. Strategies to induce ovulation include weight loss, oral
      anti-oestrogens (principally clomiphene citrate), parenteral gonadotrophin
      therapy and laparoscopic ovarian surgery. There have been no adequately powered
      randomized studies to determine which of these therapies provides the best
      overall chance of an ongoing pregnancy. Women with PCOS are at risk of ovarian
      hyperstimulation syndrome (OHSS) and so ovulation induction has to be monitored
      carefully with serial ultrasound scans. The recognition of an association between
      hyperinsulinaemia and PCOS has resulted in the use of insulin sensitizing agents,
      such as metformin, which appear to ameliorate the biochemical profile and improve
      reproductive function.

PMID- 11844365
TI  - What's new in the pathogenesis and prevention of ovarian hyperstimulation
      syndrome?
AB  - Several pathophysiological mechanisms have been proposed for the development of
      ovarian hyperstimulation syndrome (OHSS), such as activation of the ovarian renin
      -prorenin--angiotensin system, release of ovarian cytokines and nitric oxide, but
      numerous reports now attest to the role of vascular endothelial growth factor
      (VEGF), an endothelial cell mitogen, as an important mediator of the syndrome.
      Luteinizing hormone (LH) or human chorionic gonadotrophin (hCG) regulates VEGF
      production by the ovary. Formation of multiple follicles, as seen in regimens of
      ovarian stimulation used for in vitro fertilization (IVF), and intensified
      sensitivity towards human menopausal gonadotrophin (hMG) and hCG, as seen in
      women with polycystic ovaries (PCO) or polycystic ovary syndrome (PCOS), result
      in increased serum VEGF concentrations, probably due to enhanced VEGF production
      by the ovaries. It is possible that the hypersecretion of VEGF in women with PCO
      is due to an increase in the number of VEGF secreting cells or that the cells
      individually hypersecrete VEGF. This hypothesis was tested by in vitro studies on
      granulosa lutein cells. After the cells were stimulated with gonadotrophins and
      hCG, VEGF production was higher in granulosa cells obtained from women with PCO
      compared with those obtained from women with normal ovaries under similar culture
      conditions. The studies performed in vivo and in vitro were consistent with
      increased VEGF expression as a constitutive feature of PCO. Increased VEGF may be
      responsible for the fluid shift from the vascular bed to the extravascular space,
      which characterizes OHSS. Prevention of OHSS focuses on predicting the
      possibility of developing OHSS. Markers such as serum oestradiol concentrations
      and number of follicles on the day of hCG administration, the presence of PCO and
      the number of oocytes retrieved may be subject to inter-observer and inter
      operator variations. As individual markers of OHSS, each of these factors
      predicts less than a quarter of cases of the syndrome. It has been shown that a
      combination of pretreatment diagnosis of PCO along with number of follicles on
      the day of hCG administration and 'VEGF rise' gives the highest prediction rates
      for the risk of developing OHSS. Neither pathogenesis nor prevention and
      treatment of OHSS are specific. Therefore, at present, OHSS remains a condition
      that cannot be avoided altogether.

PMID- 11844366
TI  - Has clinical practice been changed by the Human Fertilisation and Embryology Act
      1990?
AB  - The birth in 1978 of the first baby to be conceived through in vitro
      fertilization caused both wonder and controversy. Concerns that this technology
      would be abused led the Government of the United Kingdom to appoint a Committee
      of Enquiry into human fertilization and embryology, which led to the publication
      in 1984 of what has become known as the Warnock Report. This made recommendations
      on the creation of human embryos in vitro, the storage of human eggs, sperm and
      embryos, and research on human embryos. This report led eventually to the passing
      by Parliament of the Human Fertilisation and Embryology Act 1990 and the creation
      of the Human Fertilisation and Embryology Authority, which since 1991 has
      licensed and regulated all centres and practitioners of assisted reproductive
      technology. The effects of these regulations are considered in this article.
      Clinical practice has been affected by the Act, but it has generally led to
      higher standards of clinical and laboratory practice, improved patient
      information and care, and improved ethical standards.

PMID- 11844367
TI  - Establishing an intrauterine insemination programme from a nursing perspective.
AB  - The Centre for Reproductive Medicine in Bristol has been performing simple donor
      insemination for more than 10 years. Evidence indicates that intrauterine
      insemination using donated sperm results in higher success rates than
      intracervical insemination (Ford et al., 1997). As donor insemination at the
      Centre for Reproductive Medicine gives an overall success rate of 10% (January
      1998 -- July 1999), which compares very favourably with other centres licensed by
      the Human Fertilisation and Embryology Authority, the decision was taken to
      continue to offer this as the primary service and in addition to offer
      intrauterine insemination to certain categories of women. Extending the well
      established donor insemination service to include intrauterine insemination was a
      natural progression for nurses already skilled in this area. The aim of this
      article is to share with other healthcare professionals the key involvement of
      specialist fertility nurses in the development of an intrauterine insemination
      programme.

PMID- 11844369
TI  - Editorial.

PMID- 11844368
TI  - Reproductive issues from the Islamic perspective.
AB  - The Islamic faith is regarded by its followers, Muslims, as a complete way of
      life. A multitude of nationalities practise Islam and also various sects, and as
      a result there are various interpretations of Qur'anic guidance relating to
      almost every matter. Only a fully qualified jurist of the highest rank can issue
      edicts on problems that are not already clearly addressed in the Qur'an. This
      applies to contemporary issues and any Muslim is at liberty to debate and
      dialogue with the religious leader to obtain a ruling on a specific question.
      Marriage is described as half the faith in Islam and to have children is seen as
      a great blessing. There is no religious objection to an infertile married couple
      pursuing any form of infertility treatment including in vitro fertilization,
      surgical sperm retrieval and micro-assisted conception methods. However, there
      must be strict control to ensure that the gametes belong to the husband and wife.
      This relationship is described as 'halal' (permitted), whereas any union of
      gametes outside a marital bond, whether by adultery or in the laboratory, is
      'haraam' (forbidden). Therefore, donor sperm pregnancies are strictly forbidden
      in all schools of Islamic law. The advent of ovum donation and surrogacy has led
      some Islamic scholars to allow this procedure between co-wives thereby avoiding
      the 'haraam' relationship between sperm and egg, but there is still debate on the
      definition of the mother. Similarly, treating any other situation outside a
      marriage relationship, for example fertilization of an ovum from cryopreserved
      sperm after divorce of the couple or death of the husband would be 'haraam' and
      strictly forbidden. The Qur'anic guidance is quite clear that the couple can
      pursue all permitted treatments but may need to accept that they may not achieve
      a pregnancy. Adoption is encouraged in Islam with the specific rule that the
      child must be able to identify its biological father by keeping his name. It must
      be emphasized that Muslims will vary on their degree of adherence to the faith
      and the practitioner should present all the options to the couple without
      assuming which treatments they will or will not accept.

PMID- 11844370
TI  - Rationing fertility services in the NHS: a provider's perspective.

PMID- 11844371
TI  - Invited commentaries on the Royal College of Obstetricians and Gynaecologists'
      guidelines on the management of infertility in tertiary care.

PMID- 11844372
TI  - BFS Recommendations for Good Practice on the Screening of Egg and Embryo Donors.

PMID- 11844374
TI  - The experience of chairing the Association of Clinical Embryologists through its
      formative years.

PMID- 11844373
TI  - British Andrology Society Workshop: sperm interactions with epithelia and their
      products.
AB  - The British Andrology Workshop entitled Sperm interactions with epithelia and
      their products focused on the contribution of epididymal and oviductal epithelia
      and seminal fluid to the development of sperm function. The workshop also
      featured a state-of-the-art lecture entitled 'Activation of amino acid
      neurotransmitter receptor/chloride channels and sperm function'. Topics explored
      in the main body of the workshop included: the signalling pathways that might be
      functional in spermatozoa; whether differential subcellular localization of
      potential pathway components might play a role; what information could be gained
      from non-sperm cells; and the role of steroid hormones as potential effectors in
      sperm signal transduction. Tyrosine phosphorylation of downstream target proteins
      in spermatozoa was discussed and data were presented that supported a role for
      fertilization promoting peptide (FPP) in regulating sperm function in the female
      tract. Speakers revisited and challenged the idea that specific epididymal
      secretory proteins play a direct and active part in sperm functional maturation
      and raised the possibility that through binding and integration of DNA,
      spermatozoa could act as a vector for the incorporation of foreign genetic
      information. The roles of hyaluronic acid in maintaining sperm viability and
      promoting sperm capacitation and as a marker of sperm maturity were explored.
      Data were presented on sperm storage in birds. The workshop concluded with
      presentations on the potential roles of direct binding of spermatozoa to
      oviductal cells and their interaction with oviductal fluid components in the
      final preparation for successful fertilization.

PMID- 11844375
TI  - Fertility nurses doing embryo transfers -- what is the impact of training?
AB  - It has been demonstrated that embryo transfer during IVF treatment can be
      performed competently and successfully by nurses (Barber et al., 1996). The
      present study has examined the success of nurses in training using the
      standardized protocol of this Unit. Initially, three nurses (two experienced
      (training completed) and one inexperienced (training ongoing)) each performed 80
      transfers, which were standardized to three embryos replaced per transfer. The
      study aimed to establish whether a standardized procedure was undertaken by the
      nurses and to assess the influence of one inexperienced nurse performing the
      procedure. A further study (study 2) was performed to assess the influence of
      three inexperienced nurses against three experienced nurses undertaking the same
      procedures. In study 1, the pregnancy rates were 27.5%, 38.8% and 40.0% and there
      was no significant difference in the clinical pregnancy rates. In study 2, the
      pregnancy rates were 18.7%, 20.0% and 20.0% for the inexperienced nurses, and
      26.3%, 30.0% and 32.5% for the experienced nurses. There was no significant
      difference in the clinical pregnancy rates within the inexperienced group or the
      experienced group. When the results of the three inexperienced nurses were
      grouped and were compared with those of the three experienced nurses, the
      pregnancy rates were 19.5% and 29.5%, respectively (P < 0.02). It has been shown
      that good clinical pregnancy rates can be achieved when nurses perform embryo
      transfer. There is no significant effect on clinical results when one nurse is in
      training; however, because of the expected learning curve, when three nurses
      train together a more significant effect is observed.

PMID- 11844376
TI  - The impact of the quality of family planning services on safe and effective
      contraceptive use: a systematic literature review.
AB  - The aim of this review is to identify the features of family planning service
      provision that are influential in ensuring safe and appropriate contraceptive use
      and optimal effectiveness of user-dependent methods. A systematic search was
      carried out of the published and unpublished studies available up to December
      1997 that examined the relationship between family planning service provision and
      contraceptive use. Articles that reported primary data on long-term outcomes were
      scored by at least two of the authors of the present study. Particular attention
      was paid to evaluating methods of measuring quality of care. A total of 142
      articles were identified, but only 16 reported primary data relating to long-term
      outcomes. The quality of provider--client exchanges was found to have a net
      incremental effect on contraceptive use. Evidence of effectiveness of methods to
      improve uptake, continuation of method use, and safe and appropriate use of
      fertility control is scant. The evidence that is available indicates that
      training in communication with clients (particularly about side-effects of
      contraceptive methods) and an emphasis on client choice are key components of
      effective interventions. The tasks of listening to clients, and tailoring
      services to local needs, are crucial to the success of family planning service
      provision.

PMID- 11844377
TI  - Blood flow changes in the ovarian and uterine arteries in women with normal and
      polycystic ovaries.
AB  - This review summarizes the haemodynamic changes in the ovarian and uterine
      arteries, as revealed by transvaginal colour Doppler ultrasonography, (i) in
      women with normal ovaries (group 1), (ii) in women with the polycystic ovary
      syndrome who ovulate in response to clomiphene citrate (group 2) and (iii) in
      women with polycystic ovaries who have a regular ovulatory menstrual cycle (group
      3). In each group blood flow velocities in the intraovarian arteries increased
      during the menstrual cycle in the dominant ovary and remained high in the mid
      luteal phase. There was no significant change in pulsatility index. In group 2,
      the longitudinal haemodynamic changes in the intraovarian arteries were similar
      to those seen in women with normal ovaries. However, the follicular and ovarian
      stromal blood flow velocities were greater in group 2 compared with the normal
      group. There was a significant increase in the pulsatility index of the uterine
      artery during the follicular phase of the menstrual cycle and a subsequent
      decrease into the mid-luteal phase. Uterine artery pulsatility index was also
      significantly greater at the baseline ultrasound scan in group 2. In group 3, the
      longitudinal haemodynamic changes in the intraovarian arteries were similar to
      those in group 1. Furthermore, the intraovarian vascular changes were similar to
      those in group 2, but velocities were significantly greater than in group 1.
      There was an increase in uterine artery pulsatility index during the follicular
      phase of the menstrual cycle and a subsequent decrease into the mid-luteal phase.
      The uterine artery Doppler changes were similar to those seen in group 2. In
      conclusion, women with polycystic ovaries have significant differences in ovarian
      and uterine artery haemodynamics. Increased ovarian stromal blood flow within the
      polycystic ovary may help to explain the increased ovarian re-sponsiveness that
      women with polycystic ovaries show after administration of gonadotrophins.

PMID- 11844378
TI  - Using prognostic models in clinical infertility.
AB  - The chance that a couple who have tried to conceive for 12 months will succeed
      without assisted conception treatment is still higher than the chance that the
      same couple will benefit from treatment. In this context, it is important to
      assess the chance that a treatment-independent or 'spontaneous' pregnancy will
      occur in a couple whose wish for a child is unfulfilled. Prognostic models can be
      useful in this assessment. In recent years, prognostic models have been published
      both for the occurrence of 'spontaneous' pregnancy and for pregnancy after in
      vitro fertilization. This article discusses the theoretical aspects of prognostic
      modelling and assesses whether the current prognostic models are good enough to
      justify their use in clinical practice. The performance of existing models for
      the prediction of spontaneous conception was found to be acceptable on internal
      as well as on external validation. However, the performance of the existing
      models predicting IVF outcome was found to be disappointing on the few occasions
      on which such external validation has been performed.

PMID- 11844379
TI  - Value of thyroid function tests in routine screening of women investigated for
      infertility.
AB  - Women presenting with infertility traditionally have been screened for thyroid
      function, yet recent guidelines have indicated that this is unnecessary in
      asymptomatic patients. A retrospective analysis of the results of routine thyroid
      function screening showed that occult thyroid dysfunction is common: 5.1% of the
      population studied had abnormal thyroid function tests. Therefore, it is
      recommended that assessment of thyroid function in women attending an infertility
      clinic should be continued.

PMID- 11844381
TI  - In vitro fertilization: a long-term follow-up after treatment failure.
AB  - There is a considerable body of psychological research on women presenting for in
      vitro fertilization (IVF), but relatively little on the long-term adjustment of
      such women after unsuccessful treatment. This study examined the adjustment (4--9
      years after treatment) of a sample (n = 76) of women whose treatment had failed.
      At follow-up, it was found that eight (10.53%) of the women had conceived
      naturally and 16 (21.05%) had become adoptive parents. In comparison with
      population norms, the women who had not subsequently conceived or adopted (n =
      52) were found to rate themselves as more highly stressed (P < 0.001), but rated
      themselves as higher in self-esteem (P < 0.001). However, when women who remained
      childless after unsuccessful IVF were compared with those who subsequently
      conceived or adopted, the former group rated themselves as more stressed (P <
      0.05), more depressed (P < 0.001) and with a lower satisfaction with life (P <
      0.005) and lower self-esteem (P < 0.05). Women who wished to adopt but were
      unable to do so made a major contribution to this negative pattern. The study
      indicates that infertility long after failed IVF treatment contributes to
      psychological dysfunction. It highlights the need to prepare women better for
      treatment failure and to ensure appropriate counselling is available when further
      IVF treatment is no longer appropriate.

PMID- 11844380
TI  - Pregnancy and miscarriage rates in 3978 donor insemination cycles: effect of age,
      parity and partner's infertility status on pregnancy outcome.
AB  - The effects of age, parity and male infertility status on pregnancy outcome were
      studied in a cohort of 720 women receiving donor insemination (DI) treatment.
      Twenty-two percent of women failed to complete the treatment, leaving 562 women
      receiving 3202 cycles of DI for assessment. Of the 321 of pregnancies achieved,
      57 (17.8%) ended in a miscarriage. After further DI treatments, 64.7% of mothers
      who had miscarried succeeded in giving birth. There was some evidence to indicate
      a trend of decreasing pregnancy rate with increasing maternal age, although this
      result was not significant (log rank trend statistics = 3.44, P > 0.05). The
      pregnancy rates of multiparous and primiparous women were significantly
      different, irrespective of their partner's infertility status (azoospermia: log
      rank statistics = 3.74, P less-than-or-eq, slant 0.05; oligozoospermia: log rank
      statistics = 4.71, P < 0.03). Furthermore, multiparous women were more likely to
      become pregnant than primiparous women (azoospermia: hazard ratio = 1.29;
      oligozoospermia: hazard ratio = 1.50). There was no significant association
      between miscarriage rate and maternal age (log rank trend statistics = 0.99, P >
      0.05). The small number of older women (> 35 years) may confound this result. The
      mean (plus minus SD) sperm donor age was 23.6 years (plus minus 3.5 years). The
      implications of these observations are discussed.

PMID- 11844382
TI  - Intracytoplasmic sperm injection in assisted reproductive technology: an
      evaluation.
AB  - Since the first reports of successful pregnancies in humans after treatment with
      intracytoplasmic sperm injection (ICSI), intensive investigations have focused on
      several important aspects of this form of assisted reproductive technology. In
      addition to the technical development of ICSI and increasing understanding of the
      biochemical and biophysical processes involved during fertilization after
      injection of an immobilized sperm, studies have aimed to define the indications
      for patients for a first-line ICSI treatment. One of the major concerns is of
      course the safety of the technique in terms of the health and reproductive life
      of the babies born after ICSI. The rhesus monkey is an excellent model to
      investigate all aspects of this micromanipulation technique. This article
      provides an evaluation of ICSI.

PMID- 11844383
TI  - Overview: Are blastocysts better?

PMID- 11844384
TI  - Blastocyst culture: toward single embryo transfers.
AB  - The routine culture and transfer of viable human blastocysts has been made
      possible by the development of sequential culture media, formulated to account
      for the changes in nutrient requirements of the embryo as it develops and
      differentiates. Resultant implantation rates of blastocysts transferred on day 5
      are significantly higher than those obtained by the transfer of cleavage stage
      embryos transferred on day 2 or day 3 within the same programme. As a direct
      result of this increase in implantation rate, fewer blastocysts than cleavage
      stage embryos need to be transferred to obtain acceptable pregnancy rates,
      thereby reducing the incidence of multiple gestations. Blastocysts developed in
      sequential culture media are readily cryopreserved. The efficiency of in vitro
      fertilization (IVF) in a general patient population can be calculated using a
      model that takes into account the number of embryos transferred and
      cryopreserved, together with their respective implantation rates. Blastocyst
      transfer is associated with about a 20% increase in the efficiency of IVF
      compared with the transfer of cleavage stage embryos on day 3. The development of
      a suitable scoring system has enabled identification of those blastocysts with
      the highest developmental potential (70% implantation rate). The culmination of
      this work should be the move to the transfer of a single blastocyst for a
      significant number of patients.

PMID- 11844385
TI  - Large offspring syndrome and other consequences of ruminant embryo culture in
      vitro: relevance to blastocyst culture in human ART.
AB  - In vitro production of embryos from domestic animals is used to augment
      conventional genetic improvement programmes in agriculture and to facilitate
      advances in gene transfer and cloning. However, production of embryos in vitro
      exposes them to hazards not normally encountered in vivo and, as a result, there
      have been unforeseen consequences including the large offspring syndrome. This
      syndrome is manifest as abnormal growth and development at fetal, neonatal and
      later stages after transfer of embryos cultured in vitro for up to 1 week after
      fertilization. Our embryo culture and fetal development studies have begun to
      characterize many of the genetic, metabolic and developmental features associated
      with the syndrome. This review considers the findings of these studies in the
      context of blastocyst production in vitro, emphasizing the impact of culture
      strategies on ruminant (cattle and sheep) embryo composition and developmental
      competence. The need to alter in vitro production strategies to safeguard oocytes
      and embryos during culture is discussed. Finally, the implications of experiences
      gained in domestic animal studies are considered in the context of current
      options for human embryo culture. The need for an appreciation of the sensitivity
      of the embryo to its environment and the possible short- and long-term
      consequences of inappropriate in vitro production strategies are considered.

PMID- 11844386
TI  - Nutritional and metabolic requirements of early cleavage stage embryos and
      blastocysts.
AB  - During preimplantation human embryo development there is an increase in the
      synthesis of macromolecules and a demand for energy. Consequently, the metabolic
      requirements of the human embryo change as development proceeds from the zygote
      to the blastocyst stage. Evidence from a number of species indicates that before
      activation of the embryonic genome, human and other mammalian embryos have a
      preference for oxidizable energy substrates, particularly pyruvate, non-essential
      amino acids and glutamine. After embryonic genome activation, glucose and
      essential amino acids become increasingly important. As such, there is a switch
      in energy metabolism during preimplantation development from one based
      principally on aerobic respiration, to another based on oxidative metabolism and
      aerobic glycolysis.

PMID- 11844387
TI  - Meeting Report: 2008: a turning point for truth? Counselling and legislation in
      the future.

PMID- 11844388
TI  - Issues of confidentiality in fertility counselling.
AB  - Confidentiality is arguably the most frequent source of ethical dilemmas for
      counsellors of all types, but especially those working within or alongside
      multidisciplinary teams in clinical settings. Infertility counsellors fall within
      this category and are frequently faced with difficult decisions about what issues
      to treat as strictly confidential to the counselling relationship and when to
      disclose information to other members of the clinical team. This article examines
      the professional parameters within which infertility counsellors make these
      decisions under the Human Fertilisation and Embryology Authority (HFEA) Code of
      Practice. These parameters place considerable reliance on the professional
      judgement of the counsellor, which raises the issue of how best to conceptualize
      these dilemmas. The second part of this article examines how some counsellors
      working in a closely related field, namely HIV counselling, have ameliorated this
      dilemma by distinguishing ethical stances appropriate to different circumstances.
      The positive response of participants at the British Infertility Counselling
      Association Conference at the Tavistock Centre in London on 25 May 1999 suggests
      that this type of ethical framework would be useful for informing the ethical
      decision-making of these counsellors and developing a positive appreciation of
      ethical diversity of practice within the multidisciplinary team. The final
      sections of this article examine these potential applications.

PMID- 11844389
TI  - Developing the clinical nurse specialist's role in fertility: do patients
      benefit?
AB  - This article discusses the published studies surrounding the role of the clinical
      nurse specialist and its effect on patient care. Evidence is presented to
      indicate that the extended role of the clinical nurse specialist provides a
      positive benefit when centred on patient need. Fertility nurses have responded to
      the rapid developments within the field and demonstrated that they can deliver a
      high level of practice within assisted reproduction clinics. This article focuses
      on some of the areas of extended fertility nursing practice.

PMID- 11844390
TI  - Rationing fertility services in the NHS: the patients' viewpoint.
AB  - The aim of this article is to give the patients' viewpoint on the provision of
      infertility services by the NHS, to discuss how patients see this provision as a
      form of rationing and to consider the ethical aspects of this situation. Most
      patients seeking treatment to enable them to conceive are treatable and therefore
      the term subfertility should be used rather than infertility. Fertility services
      such as the NHS do not ration contraception and obstetric care, so why should
      subfertility services be different? Access to treatment is entirely dependent on
      where a patient lives and this situation is totally unethical. The area of
      reproductive medicine in which this inequality is most apparent is assisted
      reproductive treatments such as in vitro fertilization. The situation in the UK
      varies widely and this variation will soon become more marked as the Scottish
      Office Department of Health has announced a national service framework for
      commissioners of subfertility services that will ensure equity for patients. What
      about the rest of the UK? There are some areas in England and Wales that are
      quite well funded, but there are still many health authorities that refuse to
      fund assisted conception techniques, and in Northern Ireland there is no funding
      for these treatments. The emotional aspects of subfertility must not be
      forgotten: patients experience depression, tearfulness, anger, grief and, most
      worrying of all, some experience suicidal feelings. The changes to the system in
      Scotland were mainly due to patients and professionals campaigning together, as a
      partnership. Their success should be an example to the rest of the UK.

PMID- 11844391
TI  - Rationing and NHS fertility services: a commissioning perspective.
AB  - Of all NHS services, infertility appears to suffer the most from inequity or
      unfairness of provision across the UK. Infertility is a significant cause of
      population ill health and emotional morbidity which can be managed effectively
      and relatively cheaply. Although longing for a 'take home baby', most patients
      know that their planned treatment cannot guarantee success. They are aware of the
      scarcity of resources and of the need for their appropriate allocation. However,
      patients also expect to have their problem carefully assessed and appropriately
      treated by the best methods of assisted conception currently available and that
      this will be done fairly, given their particular clinical and demographic
      circumstances. Commissioners and clinicians have a duty to acknowledge
      infertility as a significant health need and to ensure that the treatment
      provided is both equitable and as effective as possible. This article outlines a
      local model of commissioning and provision of infertility services that may be of
      interest and value to those in the process of redesigning infertility services. A
      recently published Scottish Expert Report on infertility services in Scotland
      also offers a positive way forward in this arena.

PMID- 11844392
TI  - The economic consequences of multiple gestation pregnancy in assisted conception
      cycles.
AB  - This study estimates the projected costs of multiple births resulting from
      assisted conception cycles (in vitro fertilization with or without
      intracytoplasmic sperm injection and ovarian stimulation with gonadotrophin). The
      estimates are modelled from the volume of services, treatment success and
      multiple gestation rates in recent registry data. The coverage is restricted to
      hospital costs associated with delivery and the trends are projected to 2000 in
      the United States. Sensitivity analyses tested different assumptions about per
      annum trends in effectiveness, multiple pregnancy rates and health costs. The
      national cost of in vitro fertilization cycles is US$470.2 million (L313.5
      million) and the cost of the multiple pregnancies from in vitro fertilization is
      US$639.9 million (L426.7 million). The national cost of ovarian stimulation
      cycles is US$166.6 million (L111.1 million) and the cost of the multiple
      pregnancies from ovarian stimulation is US$257.3 million (L171.6 million).
      Although costs are a limited indicator of the burden of illness, the projected
      national cost of multiple pregnancy associated with assisted conception in 2000
      is greater than the base cost of the treatment. Prevention of multiple pregnancy
      in assisted conception cycles should be a priority.

PMID- 11844393
TI  - Chair's Message - Planning for the Future.

PMID- 11844394
TI  - Editor's Message - Welcoming a New Direction and a New Editor.

PMID- 11844395
TI  - Diet and Environmental Illness: Barriers Encountered by Women Sufferers.
AB  - Environmental illness is characterized by an ill-defined constellation of signs
      and symptoms of unknown etiology. It is assumed that exposure to low dose
      irritants in the environment initiates a chronic and relapsing disorder in
      susceptible individuals. Although diet is central in the treatment of
      environmental illness, there is little research to describe how those living with
      environmental illness view diet and the barriers they encounter. The objective of
      this work was to look at the perceptions of food and nutrition in a small group
      of women with a confirmed diagnosis of environmental illness so as to identify
      common barriers to meeting food needs and to suggest roles for
      dietitians/nutritionists in assisting those with environmental illness. Eight
      subjects recruited from a government sponsored Environmental Illness Clinic
      participated in focus group discussions. Following each session, transcripts were
      coded and used to generate categories and crosslinks. The most significant
      barrier encountered by all subjects was the financial cost, be it for treatment,
      purchasing special foods and nutrient supplements, or misdiagnosis. The next most
      important variable was time required to complete activities of daily living.
      Although all participants followed a special diet, this alone was not perceived
      to be an intrusion. All subjects commented on the social isolation and the way
      the diagnosis of environmental illness had altered all aspects of their life.
      Participants identified education and advocacy as the most important areas where
      dietitians/nutritionists could make a contribution to the health and well-being
      of this nutritionally vulnerable group.

PMID- 11844396
TI  - Student and Parent Response to Use of an Early Childhood Nutrition Education
      Program.
AB  - A quasi-experimental pretest-post-test design was used to evaluate the impact of
      an early childhood nutrition education program on kindergarten students'
      familiarity with and stated willingness to eat 16 test foods. Thirteen classes of
      students were randomly assigned to control or intervention groups. The
      intervention groups were introduced to eight of the test foods using the program.
      Sixteen plastic food models, including the foods introduced in the program, were
      presented to each student at pretest and post-test seven months later. Students
      named foods they were familiar with and stated if they were willing to eat each
      food. Pretest and post-test parental questionnaires queried which of the 16 foods
      listed they thought their child was willing to eat. Familiarity with introduced
      foods increased over time in the intervention (P<0.0001) and control groups
      (P<0.01), but there was no significant increase in stated willingness to eat
      either introduced or non-introduced foods for either subject group. However,
      significantly more parents of the intervention group (P<0.001) than control group
      children reported their child had mentioned exposure to a food at school when
      requesting it at home. Children consistently stated they were willing to eat a
      greater number of foods than their parents perceived. The modest impact of this
      program draws attention to many factors nutrition educators must consider when
      evaluating early childhood nutrition education programs.

PMID- 11844397
TI  - Body Image Dissatisfaction: A Framework of Development and Recommendations for
      Dietitians.
AB  - Body image dissatisfaction is a serious, prevalent condition in western culture.
      It is estimated that 50% of women dislike their bodies and fear being overweight;
      two manifestations of a negative body image. There has been a trend in recent
      years for more and more individuals to experience a discontent with their bodies.
      Body image dissatisfaction is not simply a dislike of personal appearance, but
      the negative emotions, thoughts and attitudes associated with perceived
      appearance. Consequently, assessment and therapy of this condition involves the
      understanding of intricate psychological processes. Body image dissatisfaction
      may prevent individuals from incorporating other healthy behaviours, including
      balanced approaches to nutrition and activity. Dietitians routinely counsel
      individuals in the area of nutrition and health, yet dietitians are usually
      untrained to recognize body image dissatisfaction. This review examines the
      condition of body image dissatisfaction and provides the necessary background
      information to understand its development. Recommendations for dietitians are
      included to assist those working with affected individuals.

PMID- 11844398
TI  - Chair's Message - A Time of Paradoxes.

PMID- 11844399
TI  - Editor's Message - The Challenge of Dietary Assessment.

PMID- 11844400
TI  - Menu Analysis for Improved Customer Demand and Profitability in Hospital
      Cafeterias.
AB  - Several sophisticated menu analysis methods have been compared in studies using
      theoretical restaurant menus. Institutional and especially hospital cafeterias
      differ from commercial restaurants in ways that may influence the effectiveness
      of these menu analysis methods. In this study, we compared three different menu
      analysis methods - menu engineering, goal value analysis, and marginal analysis
      in an institutional setting, to evaluate their relative effectiveness for menu
      management decision-making. The three methods were used to analyze menu cost and
      sales data for a representative cafeteria in a large metropolitan hospital. The
      results were compared with informal analyses by the manager and an employee to
      determine accuracy and value of information for decision-making. Results
      suggested that all three methods would improve menu planning and pricing, which
      in turn would enhance customer demand (revenue) and profitability. However, menu
      engineering was ranked the easiest of the three methods to interpret.

PMID- 11844401
TI  - A Qualitative Study of Community Kitchens as a Response to Income-Related Food
      Insecurity.
AB  - A variety of self-help and community development strategies have recently emerged
      to address problems of hunger and food insecurity at a local level. One such
      strategy is community kitchens. Loosely defined as community-based cooking
      programs, "kitchens" are groups of people who regularly come together to prepare
      food for themselves and their families. This study employed grounded theory
      methods to examine the potential of community kitchens to enhance food security
      among those with constrained resources. Insights gained from participant
      observations of ten kitchens in progress were augmented by in-depth interviewing
      of a sample of participants and facilitators. Study findings suggest that, in
      some cases, community kitchen participation may enhance coping skills and provide
      valuable social support. However, the programs have limited potential to resolve
      food security issues rooted in severe and chronic poverty because they do not
      alter households' economic circumstances in any substantial way.

PMID- 11844402
TI  - Development and Application of a Pediatric Anthropometric Evaluation System.
AB  - Children with developmental disabilities are at increased nutritional risk
      because of feeding problems, abnormal levels of physical activity, and altered
      weight and growth patterns. Children with physical disabilities are often more
      difficult to measure because of muscular contractures, spasms, scoliosis, and the
      presence of splints, braces, or wheelchair accessories. In addition, body weights
      may be difficult to obtain for heavier children with limited access to wheelchair
      scales. The purpose of this project was to produce a package of anthropometric
      measurements easier to use in children with physical disabilities but still
      applicable to able-bodied children, and computer software to generate growth
      charts. The project included the development of growth charts for each
      anthropometric measurement, using data from the Coquitlam Growth Study (921
      children aged six to 18) and the Sunny Hill Growth Study (567 children aged one
      to 5.9). The custom computer software allows serial plotting of a child's
      measurements on growth charts, permitting comparative assessment of growth and
      muscle and adipose tissue development. The resultant Sunny Hill Anthropometric
      Pediatric Evaluation System (SHAPES) provides a tool for nutritional assessment
      and monitoring after intervention. The use of SHAPES is illustrated with a case
      study of a child who represented a challenge to traditional nutritional
      evaluation.

PMID- 11844404
TI  - Chair's Message - What's New from the Board.

PMID- 11844403
TI  - Culture-specific food frequency questionnaires: Development for use in a
      cardiovascular study.
AB  - The object of this work was to develop self-administered, culture-specific food
      frequency questionnaires (FFQs) for use in a prevalence study of cardiovascular
      disease. The cultures included the general Canadian population, south Asian
      Canadians and Chinese Canadians and the FFQs were based on the structure of our
      previously reported FFQ used in the Canadian Diet, Lifestyle, and Health Study.
      Food record data for each of the culture groups were available from previous
      studies. A database was used to identify food items and serving sizes to be
      included in each questionnaire. The foods contributing most of the 19 food
      components of the general Canadian sample were calculated. This article describes
      the methodology for the initial development of the FFQs and discusses the initial
      evaluation of the general Canadian questionnaire. Validation of all three
      questionnaires against seven-day food records is in progress.

PMID- 11844405
TI  - Editor's Message - Journal Review Results.

PMID- 11844406
TI  - Dietary Patterns of a Group of Children, Mothers and Grandmothers.
AB  - Information regarding the dietary patterns of life cycle cohorts may reveal the
      usefulness of nutrition education messages. We described the dietary patterns of
      a convenience sample of three life stages, children, mothers and grandmothers and
      determined differences between adjacent age cohorts, for per cent of energy as
      carbohydrate, fat and protein, number of servings from food groups and intake of
      key nutrients associated with food groups. Four days of dietary intake data were
      available for 76 children (8.8 - 12.9 years), 59 premenopausal females, 31 - 52
      years (mothers) and 19 postmenopausal females, 58 - 83 years (grandmothers). The
      greatest difference was for per cent of energy as carbohydrate (mean SD), for
      which the value for mothers (48 7) was significantly lower than that for the
      children (53 5), while the grandmothers' intake (52 6) was similar to that of the
      children. Intake of Vegetables and Fruit also varied at 3.9 2 servings per day
      for children, 5.2 2 for mothers and 7.4 3 for grandmothers. The mothers' number
      of servings of Fats and Oils was significantly higher than that of the children
      and grandmothers, while children had the highest number of servings of Sweets and
      Desserts. Levels of nutrient intakes corresponded to the number of servings from
      major source food groups for each of the life-stage groups.

PMID- 11844407
TI  - Comparison of Yukon Women by Weight Loss Effort and Body Mass Index: Self
      reported Nutrition and Exercise Practices and Beliefs and Self-rated Health.
AB  - The purpose of this study was to determine the prevalence of weight loss efforts
      among women in the Yukon Territory and to assess relationships between weight
      loss effort (not trying/trying to lose weight) or weight status and self-reported
      nutrition and exercise practices and self-rated health. Data were obtained from
      711 nonpregnant, noninstitutionalized women aged >15 y participating in the Yukon
      Health Promotion Survey. Over 50% of women were trying to lose weight at the time
      of the survey. These women were more likely to believe they ate well enough to
      maintain health, to report following certain recommended nutrition practices and
      to feel they didn't exercise as much as they needed. Self-rated mental and
      emotional health and physical health, however, were lower than among women not
      trying to lose weight. Overweight (Body Mass Index (BMI) >27) and normal weight
      (BMI 20-25) women reported similar nutrition practices and beliefs, whereas
      underweight women (BMI <20) were less likely to report following certain
      recommended nutrition practices or to believe they ate well enough to maintain
      health. Overweight women reported lower overall quality of life, physical health
      and social relationships than women with BMI = 25. These results suggest that
      weight loss should not be emphasized as the primary benefit of sound nutrition
      and that dietitians should reinforce that eating well and being active are
      important to everyone, regardless of weight.

PMID- 11844408
TI  - Reliability and Validity of the Three-Day Estimated Record of Food Intake
      Provided by Parents and Caregivers of Preschool Children in Dual-Earner Families.
AB  - This study examined the reliability and validity of the three-day estimated
      record provided by parents and caregivers of preschoolers. Subjects included a
      random sample of 146 preschoolers (24-47 months) in dual-earner families. Parents
      and caregivers completed a three-day estimated record for each child. Six weeks
      later they were randomly assigned into either a group completing a second
      estimated record (Group1) as a test of reliability, or a group completing a
      weighed record (Group 2) as a test of validity. For Group 1, significant
      differences (P<0.05) in group mean intakes of energy and four of 10 nutrients
      were found; however, the magnitude of the differences was considered small.
      Similar results were found for Group 2. Intra-person variation in energy and
      nutrient intakes exceeded inter-person variation (60-90% versus 10-40% of the
      total variation). The three-day estimated record provided by parents and
      caregivers of preschool children is reliable and valid at the group level,
      however, intra-person variation affects its use at the individual level. These
      results have implications for the design of future studies of preschool children
      with employed parents where food intake must be recorded by multiple caregivers.
      Researchers and practitioners are challenged to design new, simpler methods to
      measure food intake that lend themselves to the varied eating situations of many
      preschool children today.

PMID- 11844409
TI  - Determining the Use and Perceived Effectiveness of a Point-of-Purchase Cafeteria
      Nutrition Education Program.
AB  - The Eat Smart Heart Beat Cafeteria Program (ESCP) is a point-of-purchase
      nutrition education program (PPNEP), which was developed by the Ottawa-Carleton
      Health Department (OCHD). The intent of this program was to increase the
      awareness and availability of lower-fat, higher-fibre foods in cafeterias. The
      purpose of this study was to evaluate the ESCP using a Feedback Questionnaire.
      The questionnaire was developed primarily to determine the use of the ESCP manual
      and to evaluate the users' perceived effectiveness of this program. Purchasers of
      the ESCP were asked to complete the questionnaire one year after they received
      the program resources. Forty of the 88 program recipients (45%) returned the
      questionnaire. Most responses were from nutritionists or dietitians, health
      service managers and occupational health workers. Most respondents represented
      large workplaces (more than 250 employees) such as hospitals, government, health
      units and educational institutions. Of the 40 respondents, 10 implemented the
      program and indicated that they were moderately to very satisfied with all of the
      resources and that they would continue using the program. The 30 respondents who
      reported not using the program indicated that this was mainly due to time
      constraints. The ESCP has the potential to increase the awareness and
      availability of lower-fat, higher-fibre foods. Therefore, it is recommended that
      the program be continued in a ready-to-use format to increase its usability.
      Further research is needed to clarify the effects of the ESCP on behaviour
      change.

PMID- 11844410
TI  - Adherence to a Very Low Fat Diet for Cardiac Rehabilitation Patients.
AB  - Diets encouraging 10% or less fat energy intake have been advocated to prevent
      progression of coronary artery disease. In this study, a randomized, controlled,
      repeated measures experimental design was used to determine if reducing fat
      intake incrementally to an eventual goal of 10% of total energy intake would
      result in better dietary adherence than would an immediate reduction to 10%.
      After completing a lifestyle education program and receiving personal dietary
      counselling, volunteers recruited from a cardiac rehabilitation program
      (treatment group, n = 4; control group, n = 3) completed a 24-hour recall at two,
      four, and seven months post-intervention. At these intervals, subjects also spoke
      with the dietitian to set dietary targets for the incremental reduction group or
      reinforce them for the immediate reduction group. Neither group achieved the goal
      of reducing fat intake to 10% of total energy intake, a finding that suggests
      this may be an unrealistic target. Because both groups consumed about the same
      percentage of fat energy, there appeared to be no benefit from incremental
      reduction of fat intake as a strategy to improve dietary adherence.

PMID- 11844413
TI  - Has the level of dental fluorosis among Toronto children changed?
AB  - We conducted a survey during the 1999 2000 school year to obtain valid estimates
      of the oral health status of a probability sample of children in the 4 regions of
      the newly amalgamated city of Toronto. The results will be used in developing
      recommendations for programs to address the oral health problems identified. The
      Dental Indices System is the Ontario protocol whereby information on the oral
      health status and treatment needs of children can be obtained by direct
      assessment of the children. One of 2 specially trained dental hygienists examined
      each child's teeth and periodontal tissues using sterilized mouth mirrors and
      blunt probes with a standard light source. Overall, there were 3657 participants
      in the survey, of whom 2435 were aged 7 or 13 years; these 2 age groups formed
      the basis for the analysis. Forty percent of those aged 7 or 13 had had one or
      more decayed teeth. Approximately 7% of children in the younger age group had at
      least one condition requiring urgent care. Dental fluorosis of moderate severity
      (Tooth Surface Index of Fluorosis   2) was found among 14.0% of 7-year-olds,
      12.3% of 13-year-olds and 13.2% of the 2 age groups combined. The prevalence of
      fluorosis was of the same order as all but one of the more recent studies
      performed in Toronto. The prevalence may fall as the recently imposed reduction
      in concentration of fluorides in city water takes effect. On the basis of these
      findings of fluorosis, Toronto Public Health should continue to monitor levels of
      dental fluorosis and caries and should continue its efforts to inform parents of
      very young children about the safe use of fluoridated dentifrice.

PMID- 11844414
TI  - Use of problem-based learning in Canadian and U.S. dental schools: results of a
      survey.
AB  - Problem-based learning (PBL) is an increasingly common pedagogical method in
      health sciences education. Medicine has led the way, but many health science
      educators in other disciplines have begun to use PBL or are looking seriously at
      introducing it. There is far less information available about the extent and the
      scope of PBL in dental education than in medical education. The International
      Dental Problem-Based Learning Network (IDPBLN) is an informal group of dental
      educators interested in or involved with PBL. Representatives of the Network
      surveyed the deans of 10 Canadian and 55 U.S. dental schools to determine the
      extent of PBL in dental education. The survey included a clear definition of PBL
      to help ensure that the term was interpreted the same way by all respondents. The
      deans were asked if PBL was already used in the curriculum or if they intended to
      begin using it. For institutions where PBL was already in place, respondents were
      asked about the extent to which PBL was used in the curriculum. A total of 49
      institutions responded to the survey (9 Canadian and 40 U.S.). Twenty-two
      institutions reported that PBL was being used, and 6 of the remaining 27
      indicated that they planned to use PBL in the future. For the most part, PBL was
      used only in certain parts of the curricula, most commonly during the early
      years.

PMID- 11844415
TI  - Location of canal isthmus and accessory canals in the mesiobuccal root of
      maxillary first permanent molars.
AB  - BACKGROUND: Failure in surgical endodontics may be caused by many factors.
      Failure is commonly due to improper preparation for the root-end filling and a
      lack of seal of the resected root end. The aim of this study was to investigate
      the morphology of resected mesiobuccal (MB) root ends of maxillary first molars
      and to evaluate the location of the canal isthmus and accessory canals between
      the MB canals. METHODS: From 50 selected first permanent molars, sections of the
      MB root at 3, 4 and 5 mm from the apex were prepared, acid-etched, washed and
      dried. The apical side of each section was sputter-coated with gold, examined by
      a scanning electron microscope and photographed. RESULTS: Overall, 18 (36%) of
      the 50 MB roots had one canal, whereas 32 (64%) had 2 canals. Of the roots with 2
      canals, 10 (31.25%) contained either a complete isthmus or accessory canals or
      both between the 2 main canals. Another 10 (31.25%) showed partial isthmus
      formation. CLINICAL SIGNIFICANCE: MB roots exhibit a variety of canal
      configurations. On the basis of these findings, we propose a classification of
      the resected root surface of the MB root. Prudent judgement in preparing the
      canal isthmus, meticulous skill and comprehensive knowledge of root canal anatomy
      are essential for successful treatment.

PMID- 11844416
TI  - The dental health status of dialysis patients.
AB  - BACKGROUND: The number of patients with kidney failure who require dialysis is
      growing by 10% to 15% annually, and the likelihood that dentists will treat such
      patients is also increasing. The dental care of patients undergoing dialysis can
      be complex, given the prevalence of comorbid conditions such as diabetes,
      hypertension, renal osteodystrophy and immunosuppression, the presence of
      nondental prosthetic devices, and the use of antihypertensives and anticoagulants
      or antiplatelet agents. These patients appear to be predisposed to a variety of
      dental problems such as periodontal disease, narrowing of the pulp chamber,
      enamel abnormalities, premature tooth loss and xerostomia. Dental care, as well
      as primary preventive measures, seems to have been neglected in these patients.
      Therefore, a study of the dental health of dialysis patients was undertaken.
      METHOD: Completion of a questionnaire and a noninvasive oral examination was
      obtained from hemodialysis and peritoneal dialysis patients registered in the
      dialysis program at St. Paul's Hospital in Saskatoon, Saskatchewan, as of March
      1, 1999. Information was also gathered from the medical chart. Medication history
      as well as history of diabetes, hypertension, and nondental prosthetic devices
      were also recorded. RESULTS: Of 226 dialysis patients in central and northern
      Saskatchewan, 147 were interviewed and examined. Of these, 94 (64%) were dentate,
      and the same number had been on dialysis for a mean of more than 2 years; about a
      third were diabetic, almost all were hypertensive and all had nondental
      prosthetic devices or arteriovenous fistulae, or both. Sixty (64%) of the dentate
      patients were candidates for kidney transplantation. Most of the dentate patients
      reported brushing once or more daily, but they flossed infrequently or never.
      Dental visits were infrequent, less than every 5 years in 59 (63%) of the dentate
      patients. Findings in the dentate group included increased tooth mobility,
      fractures, erosion, attrition, recession, gingivitis and a high plaque index. A
      patient's dentist was contacted if the patient had seen him or her since starting
      dialysis (31 of the 94 dentate patients). Most (81%) of the dentists were aware
      that they were treating a dialysis patient. Medication records were incomplete
      for 29% of the patients, and only 2 (6%) of the patients had received antibiotic
      prophylaxis despite the fact that all had prosthetic devices or arteriovenous
      fistulae. CLINICAL SIGNIFICANCE: We conclude that the dental health of dialysis
      patients is poor and requires greater attention.

PMID- 11844418
TI  - Mental nerve function after inferior alveolar nerve transposition for placement
      of dental implants.
AB  - BACKGROUND: One option for successful placement of dental implants in an atrophic
      posterior mandible without injury to the inferior alveolar nerve (IAN) is to
      transpose or lateralize the nerve. This procedure carries the risk of numbness
      along the distribution of the nerve, the complication that the procedure is
      undertaken to avoid in the first place. The purpose of the present study was to
      assess mental nerve function after transposition of the IAN. METHOD: We
      determined the outcomes of 20 IAN transposition procedures in 12 consecutive
      patients at the Queen Elizabeth II Health Sciences Centre in Halifax, Nova
      Scotia. The study included objective testing of sensory nerve function as well as
      subjective assessment by the participants. RESULTS: All subjects reported initial
      transient sensory disturbance. Objective testing after a minimum of 6 months
      revealed that, for each patient, affected sites had the same level of sensation
      as unoperated areas. Eighty percent of the patients said that the lower lip and
      chin felt normal. The others said that these structures did not feel exactly
      normal but that the difference was of no consequence. CLINICAL SIGNIFICANCE: It
      is concluded that IAN transposition can be safely and predictably performed with
      low risk to the mental nerve sensibility.

PMID- 11844417
TI  - A clinical and microbiological evaluation of denture cleansers for geriatric
      patients in long-term care institutions.
AB  - BACKGROUND: Many elderly patients in long-term care hospitals cannot adequately
      brush their dentures because of disease, dementia and poor dexterity. Such
      inadequate cleaning may allow for the multiplication of Candida spp. and
      bacteria, which could serve as reservoirs for disseminating infections.
      OBJECTIVE: To assess the efficacy of 3 denture cleansers in reducing the number
      of microorganisms on dentures in a hospitalized geriatric population. METHODS:
      Three brands of cleanser (Denture Brite, Polident and Efferdent) were compared;
      water was used as the control. Microbiological samples were obtained before and
      after 3 one-week periods of cleanser use; these samples were taken by a
      microbiologist blinded to the assigned treatment. In the statistical analysis,
      the ranks of the differences between the before-treatment and after-treatment
      scores of each regimen were compared by means of the general linear model. In
      addition, the efficacy of each cleanser in reducing accumulation of plaque, stain
      and food was assessed. RESULTS: The rank of the differences in the number of
      colony-forming units (CFUs) of Candida spp. before and after one week of use of
      Denture Brite (p = 0.04) and Polident (p = 0.01), was significantly greater than
      that of the control group, but there was no difference between Efferdent use and
      control (p = 0.10). No significant differences in reduction of Streptococcus
      mutans were observed between Denture Brite (p = 0.13) or Polident (p = 0.12) and
      the control group, whereas dentures cleaned with Efferdent exhibited
      significantly greater reduction in Streptococcus mutans (p = 0.02) than dentures
      cleaned with water. Over all study periods, there were no significant differences
      among the cleansers in reduction of Candida spp. or Streptococcus mutans.
      Dentures cleaned with Denture Brite, Polident or Efferdent appeared to have
      similar reductions in the level of plaque, stain and food, and all had
      substantially greater reductions than dentures cleaned with water only. The
      significant difference in the rank of the reduction in Candida spp. CFUs (p =
      0.005) was related to the variance between study periods (p = 0.01) and the
      variance between subjects (p = 0.008). CLINICAL SIGNIFICANCE: The use of denture
      cleansers significantly reduced the number of microorganisms on dentures in a
      hospitalized geriatric population.

PMID- 11844420
TI  - [Family medicine: area of knowledge and teaching teams... An exciting project].

PMID- 11844423
TI  - [Maternal assessment of pre-natal measures to promote natural breast-feeding].
AB  - OBJECTIVES: To value the satisfaction between mothers about the different
      professionals and the prenatal promotion on breast-feeding (BF) in our basic
      health zone. To value the role of a paediatric prenatal contact in the health
      centre. DESIGN: An descriptive and retrospective, cross-sectional study based on
      an anonymous closed questionnaire filled by two groups without random selection
      defined on the variable yes/no BF. SETTING: Paediatric room in the Health Centre
      of Lugones, Health Area of Oviedo. PARTICIPANTS: Every mother of childs aged
      between 6 and 18 months attending to the Healthy Child Program since June to
      November of 2000. MEASUREMENTS AND RESULTS: 60 questionnaires were delivered, 51
      to the group BF and 9 to the group no BF (85% BF including mixed and independent
      of the duration). 52 questionnaires were collected, 44 BF and 8 no BF. We observe
      a great satisfaction in both groups on the area midwife, who is considered
      decisive. Obstetrician, hospital and primary nurse, hospital paediatrician and
      general practitioner may improve their rule in BF promotion. Both groups are
      interested in the prenatal visit with the health centre paediatrician. Women on
      no BF group thought that this interview could have changed their decision.
      CONCLUSIONS: Area midwife is considered the most value professional by the
      mothers. Hospital and primary professionals may improve his rule in BF promotion
      in our basic health zone. Only 50% women in no BF group took their decision
      before the birth. They think that the prenatal paediatric visit could have
      changed their decision.

PMID- 11844421
TI  - [Lack of iron in adolescents aged 10 to 14].
AB  - AIMS: To study the prevalence of depletion of organic iron stores, ferropenia and
      ferropenic anemia in the adolescent population in a health care district in
      northern Spain. Design. Cross-sectional, with systematic sampling. SETTING:
      Primary health care service in a rural setting. PARTICIPANTS: Sample of 204
      healthy adolescents aged 10.0 to 14.0 years; 93 males, 111 females. MAIN
      MEASURES: Familial and personal antecedents, physical activity, date of menarche,
      weight, height and body mass index, hemoglobin (Hb), mean corpuscular volume
      (MCV), transferrin saturation index (TSI) and serum ferritin (SF) were recorded
      for 1 out of every 4 adolescents who visited the health center for a regular
      check-up. Positive C-reactive protein or erythrocyte sedimentation rate were
      criteria for exclusion. Iron stores were considered to be depleted when SF was <
      12 ng/dL, ferropenia was said to exist when, in addition, TSI was < 14% or MCV
      was < 75 fL, and ferropenic anemia was said to exist when, in addition, Hb was <
      12 g/dL. RESULTS: Some stage of iron deficiency was found in 8.6% of the males
      and 12.6% of the females. Iron stores were depleted in 2.2% and 6.3%,
      respectively; ferropenia was found in 3.2% and 3.6%, respectively; and anemia was
      found in 3.2% and 2.7%, respectively. There were no significant differences
      between the sexes. CONCLUSIONS: In adolescents aged 10 to 14 years in our health
      care setting, iron deficiency was relatively common. Health care programs for
      children and adolescents should aim specifically to prevent, detect and control
      iron deficiency.

PMID- 11844424
TI  - [Factors affecting drug expenditure in the primary care centre in a health area].
AB  - OBJECTIVE: To identify the factors affecting drug expenditure.Design. Cross
      sectional study.Setting. Madrid Primary Care area. PARTICIPANTS: 21 health
      centres. MEASUREMENTS: Association of the drug expenditure per inhabitant of each
      health centre during 1999 with the characteristics of its staff and operation of
      the centre. MAIN RESULTS: Expenditure on drugs per inhabitant, 14360 plus minus
      3040 pesetas (86.31 plus minus 18.27; general practitioners, 19.62 plus minus
      23.8%; doctors working as locums, 40.48 plus minus 20.72%; women doctors, 59.76
      plus minus 13.36%; family doctors, 38.57 plus minus 21.35%; team nurses, 86.6
      plus minus 18.27%; population over 65, 18.03 plus minus 7.73%; patients per day
      attended by each general practitioner, 32.82 plus minus 3.81; number of sessions
      per year on prescription profiles, 5 plus minus 3.91; prescription avoidable
      because of health card: 3106 plus minus 808 pesetas (18.67 plus minus 4.86 );
      compliance with service offer, 1.7 plus minus 3.78. Drug expenditure per
      inhabitant dropped when sessions on prescription profiles (p = 0.013), the
      percentage of women doctors (p = 0.067) and the percentage of family doctors (p =
      0.035) increased; and it dropped too when the over-65 population (p = 0.099) and
      the amount of prescription avoidable through the card (p = 0.034) dropped. In the
      multivariate analysis, the sessions on prescription profiles (ss = -843), the
      percentage of nurses in the reformed model (ss = -155), the percentage of family
      doctors (ss = -142) and the percentage of doctors from the traditional model (ss
      = -121) explain 71.2% of the variability in drug expenditure per inhabitant (F =
      6.909; p = 0.002). CONCLUSIONS: The sessions to discuss prescription profiles,
      the presence of nurses from the reform model, postgraduate medical training and
      the employment of doctors under the traditional model are the factors that our
      study finds are linked to lower drug expenditure per inhabitant.

PMID- 11844425
TI  - [Prevalence of chronic renal failure in primary care].
AB  - OBJECTIVE: To determine the prevalence of chronic renal failure (CRF) without
      replacement treatment (RT), and to describe the primary renal diseases and
      associated risk factors that might favour its evolution to terminal renal
      failure. Design. Cross-sectional, descriptive study. SETTING: Population attended
      at a primary care centre (PCC). PARTICIPANTS: Over-14s with a clinical history
      opened at the Bon Pastor PCC. RESULTS: Between the 1st of January 1997 and the
      1st of December 1997, 12241 clinical histories were reviewed. 64 patients were
      identified who satisfied criteria of CRF without RT, a prevalence of 5228
      patients per million inhabitants (95% CI, 3,950-6,510). 71.9% were men, and mean
      age was 72 (SD, 13.5). The most recent plasma creatinine averaged 2 mg/dl (SD,
      0.66). Frequency according to kind of nephropathy was: 3 (4.7%) glomerular, 5
      (7.8%) diabetic, 3 (4.7%) interstitial, 41 (64.1%) vascular (hypertension), 2
      (3.1%) indeterminate and 10 (15.6%) unclassifiable. Associated risk factors in
      these patients were: 47 (73.4%) with hypertension, 16 (25%) diabetic, 26 (40.6%)
      with hypercholesterolaemia, 20 (31.3%) chronic consumers of analgesics, and 10
      (15.6%) smokers. 51.6% of the patients suffered other cardiovascular illnesses.
      CONCLUSIONS: The estimated prevalence in the population of CRF without RT is
      5,228 per million inhabitants. Hypertension is the risk factor most closely
      associated with this pathology.

PMID- 11844426
TI  - [Why are so few clinical trials run in primary care?].

PMID- 11844428
TI  - [Professional career and family doctors: reflections and proposal (I)].

PMID- 11844429
TI  - [Quality of life questionnaire for hypertension].

PMID- 11844431
TI  - [Prescription of antibiotics for urinary tract infection: how well it fits with
      criteria of quality in primary care].

PMID- 11844430
TI  - [Improper use of selective COX-2 inhibitor NSAIDs].

PMID- 11844432
TI  - [Slips and regressions in thinking about MIR (residency) training].

PMID- 11844433
TI  - [Emergency contraception. Information for patients].

PMID- 11844434
TI  - [Bronchoalveolar lavage in interstitial pulmonary disease. The latest news].

PMID- 11844436
TI  - [Video-assisted thoracoscopic sympathectomy: the experience of a Spanish
      cooperative group].
AB  - Preliminary results from the Spanish cooperative group for the treatment of
      palmar hyperhidrosis by video-assisted thoracoscopic surgery are presented in
      this paper. We have reviewed the cases of all patients with this disease treated
      by the group, especially noting the technique, the early results and
      complications. Video-assisted thoracoscopy emerges as the treatment of choice,
      given the ease with which the thoracic sympathetic chain can be resected, its
      safety, the lack of observed complications, and the good short-term results.

PMID- 11844435
TI  - [Spanish multicenter study of video-assisted thoracoscopy surgery].
AB  - BACKGROUND: This paper reports the findings of a prospective multicenter study
      whose main objective was to determine the indications for video-assisted
      thoracoscopic surgery (VATS), as well as the techniques used, results and
      complications. METHODS: Seventeen chest surgery units provided data on 1,573
      procedures performed over a period of two years (July 1996 to July 1998).
      RESULTS: Spontaneous pneumothorax (45.4%), lung biopsy (18.4%), pulmonary nodes
      (13.3%) and thoracic sympathectomy (5.3%) accounted for over 80% of the
      indications for VATS. An assistive mini-thoracotomy was required in 5.6%. A
      change to standard thoracotomy was needed in 167 cases (10.6%). Complications
      were observed in 10.8%, persistent air leakage being the most important.
      Spontaneous pneumo-thorax recurred in 17 cases (2.4%). Ten patients (0.6%) died.
      CONCLUSIONS: Technological developments have led to new applications for VATS as
      well as improved outcome for the most common, well established indications. It is
      advisable to continue to perform prospective, randomized, controlled trials to
      validate techniques for which little experience has accumulated.

PMID- 11844437
TI  - [Community-acquired pneumonia in the elderly: prognostic factors].
AB  - The incidence and mortality rates of community-acquired pneumonia are far higher
      in the elderly than among younger populations. However, the explanation may lie
      in the presence of comorbidity rather than in age itself. We performed a
      retrospective study of 226 patients over the age of 65 years who were admitted to
      our hospital with a diagnosis of community-acquired pneumonia over a period of 36
      months, with the objective of identifying factors predicting mortality and to
      describe clinical features. The patients' mean age was 78.71 (65-96) years. One
      hundred forty-two were men (63%) and 84 were women (37%). Upon admission, 27.4%
      showed signs of altered mental state. The crude mortality rate was 20.8%.
      Multivariate analysis demonstrated the following independent risk factors
      associated with higher mortality: serum creatinine > 1.2 mg/dL (RR = 13.93; 95%
      CI 8.14-16.08); patient previously bedridden (RR = 5.73; 95% CI 3.41-6.79),
      PaO2/FiO2 < 200 (RR = 5; 95% CI 2.67-6.62) and neoplastic disease (RR = 4.08; 95%
      CI 1.96-5.24). The presence of chest pain was associated with a lower risk of
      mortality (RR = 0.11; 95% CI 0.01-0.54). Age itself was not a risk factor. We
      conclude that pneumonia in the elderly requires hospitalization and that it
      commonly presents with severe symptoms and high risk of mortality. Risk factors
      such as those identified in this study may help in the diagnosis and treatment of
      patients requiring special care.

PMID- 11844438
TI  - [Recovery of lung function after laparoscopic cholecystectomy: the role of
      postoperative pain].
AB  - OBJECTIVES: Lung function has been shown to deteriorate after laparoscopic
      cholecystectomy (LC). The present study evaluated 1) the rate of recovery after
      LC, and 2) the pathogenic role of postoperative pain in functional deterioration.
      DESIGN: Lung function was measured 24 hours before LC, upon hospital discharge
      (48-72 h after LC), and 10 days later. All patients received metamizol after LC
      until discharge (2 g every 6 h i.v.). Half the patients (analgesia group)
      received tramadol (150 mg i.m.) 30 minutes before lung function testing on the
      day of hospital discharge. The remaining patients constituted the control group.
      PATIENTS: Twenty healthy subjects (53 4 years old) undergoing LC for gall bladder
      removal. All signed informed consent forms. Measures and outcomes: Patient
      characteristics and preoperative lung function results were similar in both
      groups. LC duration and postoperative course were also similar in both groups.
      All were discharged without complications within 72 hours after LC. Lung function
      upon discharge (FVC, FEV1, TLC, PaO2 and AaPO2) had deteriorated in both groups
      (p<0.001). Deterioration was less marked in the analgesia group (p < 0.05). Ten
      days later, lung function had normalized for all subjects. CONCLUSIONS: These
      results indicate that after LC, 1) lung function is still abnormal when the
      patient is discharged from hospital, 2) lung function has fully recovered within
      10 days, and 3) postoperative pain contributes significantly to temporary
      deterioration in lung function.

PMID- 11844439
TI  - [Characteristics of obstructive sleep apnea syndrome in patients with Down's
      syndrome].

PMID- 11844440
TI  - [Antimicrobial therapy in exacerbated chronic obstructive pulmonary disease].

PMID- 11844441
TI  - [A man with lung cancer and tuberculosis: a false positive by positron emission
      tomography and its clinical repercussions].
AB  - Positron emission tomography (PET) has come to play an increasingly important
      role in the evaluation of lung cancer patients, both for diagnostic staging and
      post-treatment follow-up. As is true for other techniques, PET gives false
      positive and negative results. False positives have been described in the
      presence of certain active infections and inflammatory lesions, such as
      tuberculous granulomas, coccidioidomycosis, aspergillosis and histoplasmosis. We
      report the case of a man whose PET gave a false positive and in whom both lung
      cancer and tuberculosis were present. A radical change in therapeutic approach
      was required, making the case interesting.

PMID- 11844442
TI  - [Occupational asthma due to amines].
AB  - A case of occupational asthma due to ethylenediamine, commonly used in different
      industrial fields, appearing in a man 56 years old who worked in the laundry
      powder industry is presented. The diagnosis was confirmed by specific bronchial
      challenge and appeared as a late bronchoconstrictive response. The appearance of
      inespecific bronchial responsiveness after the bronchial challenge is emphasized.

PMID- 11844443
TI  - [Recurrent hemoptysis due to systemic-pulmonary anastomosis of the inferior right
      phrenic artery. Treatment by percutaneous embolization].
AB  - Systemic-pulmonary-artery anastomoses resulting in a left-to-right shunt,
      regardless of the etiology, the anastomosis resulting shunt produces increased
      oxygen saturation in the ipsilateral pulmonary artery. They are radiologically
      seen sporadically in patients with hemoptisis, being main causes: traumatic,
      inflammatory or congenital, many times keeps etiology unknown. We present the
      case of a 33 year-old male with recurrent hemoptisis without etiology defined;
      his chest x-ray was reported as normal. The study was completed with broncoscopy,
      HRCT and selective arteriography, allowed diagnosis of shunt diafragmatic lower
      right artery with pulmonary artery. Finally our patient was treated by
      percutaneous transcatheter embolization.

PMID- 11844444
TI  - [On the diagnosis and treatment of bronchogenic carcinoma associated with
      spontaneous pneumothorax and bullae].

PMID- 11844445
TI  - [Mediastinal choriocarcinoma. A case report].

PMID- 11844447
TI  - [Chylothorax after pneumonectomy].

PMID- 11844446
TI  - [Severe hypoxemia due to interauricular right-to-left shunt in a patient with
      pulmonary hypertension].

PMID- 11844448
TI  - [Microbiological aspects of biomaterial-related infections].

PMID- 11844449
TI  - [Fosfomycin: an underrated antibiotic for urinary tract infections due to
      Escherichia coli].
AB  - OBJECTIVES: To evaluate the sensitivity patterns of Escherichia coli isolates
      obtained from urine specimens from patients with community-acquired urinary tract
      infections, with a special emphasis on fosfomycin trometamol for the treatment of
      UTI. METHODS: Retrospective analysis of the sensitivity pattern of 16,227 E. coli
      isolates recovered from urine cultures performed at the Microbiology Laboratory
      of Madrid Area 11 from 1997 to 2000. The antimicrobial agents tested included
      ampicillin, amoxycillin-clavulanate, cephalotin, cefuroxime, trimethoprim
      sulphamethoxazol, fosfomycin trometamol, nitrofurantoin, and ciprofloxacin.
      Antibiotic sensitivity testing was performed with the Vitek automatic
      microdilution system (bioMerieux, France). RESULTS: E. coli represented 80.1% of
      all uropathogens recovered. The percentages of sensitive strains to ampicillin,
      amoxycillin-clavulanate, cephalotin, cefuroxime, trimethoprim-sulphamethoxazol,
      nitrofurantoin, and ciprofloxacin were 42.25%, 81.5%, 58.75%, 87.5%, 70%, 94.75%,
      and 84.75%, respectively. Fosfomycin trometamol was the antibiotic with the
      highest activity against E. coli, with 95.5% of sensitive isolates. CONCLUSIONS:
      Fosfomycin trometamol (single dose) is a good alternative that should be
      considered for the treatment of non-complicated lower urinary tract infections.

PMID- 11844450
TI  - [Bronchiolitis caused by influenza type A virus. An emerging infectious disease].
AB  - OBJECTIVES: To prospectively study the emergence and diagnostic problems of
      bronchiolitis caused by influenza A virus among children durign the 1999-2000
      influenza epidemic. MATERIALS AND METHODS: Negative respiratory syncitial virus
      (RSV) specimens (ELISA dot-blot) were seeded in the MDCK cell line for the
      isolation of influenza A virus, by the shell-vial technique. Vials were revealed
      by indirect immunofluorescence with antibodies directed against the influenza A
      virus nucleoprotein (Monofluookit IA, Pasteur Diagnostics). The clinical and
      epidemiologic features of patients with viral recovery were studied. A
      theoretical cost/benefit study was performed on the usefulness of the rapid
      antigenic detection of the influenza A virus. RESULTS: A total of 117 cases of
      respiratory infection caused by influenza A virus were detected. In 62 cases
      (52.9%) the diagnosis was bronchiolitis. Of them, 80.6% of cases were aged less
      than 6 years. Subtype H3N2 predominated in all respiratory infections,
      paticularly in bronchiolitis. During the 1999-2000 season, a significant
      emergence of bronchiolitis caused by influenza A virus was observed (week 3, 30%
      cases of influenza A versus 24% of RSV). The cost/benefit study disclosed that
      the antigenic detection of RSV and influenza A virus in all respiratory specimens
      would amount up to 30.83 Euros/specimen. CONCLUSIONS: During the last influenza
      epidemic, an emergence of bronchiolitis caused by influenza A virus among
      children was observed and confirmed. Based upon this observation, a dual strategy
      should be followed. On the one hand, a prophylactic approach (immunization of
      pregnant women); on the other hand, a diagnostic approach with a rapid antigenic
      detection of the influenza A virus.

PMID- 11844451
TI  - [Cytomegalovirus sensitivity to anti-retroviral agents in patients infected with
      the human immunodeficiency virus with chorioretinitis in Spain].
AB  - OBJECTIVES: To determine the prevalence of the in vitro resistance rate of
      cytomegalovirus (CMV) to gancyclovir (GCV) and foscarnet (FOS) among patients
      with AIDS and chorioretinitis. Furthermore, in vitro sensitivity results were
      compared with the clinical response to therapy. PATIENTS AND METHODS: Thirty-six
      patients with the diagnosis of CMV retinitis and AIDS were included in the study.
      Antiviral sensitivity testing was performed to 51 clinical CMV strains from these
      patients. The in vitro sensitivity was compared with the clinical response to
      therapy. The resistance criteria were the inhibitory dose50 (ID50) GCV > 5 M and
      ID50 FOS > 400 M. RESULTS: None of the CMV tested strains was resistant to GCV or
      FOS; however, six patients who had relapses of chorioretinitis while on
      maintenance therapy and isolation during the condition had mean ID50 of strains
      (n=8) of 1,95 M for GCV (standard deviation [SD] of 0.71) and 115.2 for FOS (SD,
      34.7). These patients responded well when drugs were used at induction doses.
      CONCLUSION: The in vitro sensitivity testing is not a good predictor of infection
      control when the drug is used at maintenance doses. This suggests that these
      strains should be classified in the intermediate resistant category.

PMID- 11844452
TI  - [Staphylococcus lugdunensis infection: Report of thirteen cases].
AB  - INTRODUCTION: Staphylococcus lugdunensis is a coagulase-negative staphylococcus
      associated with infections such as aggressive endocarditis, repeated abscess
      formation and opportunist infections. MATERIALS AND METHODS: S. lugdunensis
      isolates recovered at our hospital during three years (1997-2000) were studied.
      The fibrinogen affinity factor and tube free-coagulase were analysed. The
      identification was made by the Crystal GPID (Becton-Dickinson) and Wider (Soria
      Melguizo) systems. Antibiotic sensitivity testing was performed with Wider
      panels. The clinical records of patients with S. lugdunensis recovered were
      studied. RESULTS: Thirteen S. Lugdunensis isolates were recovered from the
      following sources: abscess (9), surgical wound (2), blood culture (1), and urine
      (1). In ten cases the microorganism was obtained in pure culture; in the
      remaining three cases, S. lugdunensis grew in mixed culture. Two cases were
      excluded, as S. lugdunensis was considered not to be associated with the clinical
      condition. Lesions were located at: inguinal region (4), gluteal region (2),
      breast (2), abdominal wall (1), foot (1), unknown (1). Tent of the 13 isolates
      (76%) had fibrinogen affinity factor. Penicillin sensitivity was observed in
      11/13 strains (84.6%). In one case, the isolate was beta-lactamase producer
      (7.6%); and in other case, the isolate was resistant to methicillin (7.6%).
      CONCLUSIONS: In this study we observed that S. lugdunensis is associated with
      skin and soft tisue infections, particularly abscess formation. The infection
      occurs most frequently in cancer patients, as observed in three cases in our
      series. The necessity of correctly identifying S. Lugdunensis is underscored. The
      recovery of coagulase-negative staphylococci should not reassure us unless a
      potentially pathogen species has been ruled out.

PMID- 11844453
TI  - [Reccomendations for the diagnosis of pneumonia associated with mechanical
      ventilation].

PMID- 11844454
TI  - [Internal quality control of microbial immunodiagnosis to obtain the overall
      quality].

PMID- 11844455
TI  - [Fever and suppurative lymphadenitis in a parenteral drug user infected with the
      human immunodeficiency virus].

PMID- 11844456
TI  - [Inguinal intertrigo].

PMID- 11844457
TI  - [Preliminary evaluation of an optic immunoasay for the detection of influenza A
      virus from nasopharyngeal aspirates].

PMID- 11844458
TI  - [Infective fungal endocarditis].

PMID- 11844459
TI  - [Ophthalmomyasis due to Oestrus ovis].

PMID- 11844460
TI  - [Avascular necrosis of the femoral head among patients infected with the human
      immunodeficiency virus on antiretroviral therapy].

PMID- 11844461
TI  - [Low incidence of Lyme's disease in Northwestern Galicia].

PMID- 11844462
TI  - [Psoas muscle abscess due to Salmonella enteritidis. Case report].

PMID- 11844463
TI  - [Lymphocutaneous syndrome due to Mycobacterium marinum in a young aquarium
      enthusiast].

PMID- 11844464
TI  - [Abscessified tuberculous cavity due to a rapid superinfection by Gemella
      haemolysans overgrowth].

PMID- 11844465
TI  - [Can we prevent tick-borne transmitted diseases?].

PMID- 11844466
TI  - Trimetazidine as a potential neuroprotectant in transient global ischemia in
      gerbils: a behavioral and histological study.
AB  - The effect of Trimetazidine (TMZ) as a potential neuroprotectant against stroke
      was studied in the gerbil model of transient forebrain global ischemia. Animals
      were subjected to a 5-min period of ischemia and assessed 4 and 21 days later.
      Gerbils were divided into two groups: in group one, gerbils were treated with TMZ
      at a dose of 25 mg/kg given by intraperitoneal injection prior to ischemia. In
      group two, gerbils were treated with TMZ at a dose of 25 mg/kg given
      intraperitoneally after ischemia. Saline-injected gerbils served as controls.
      Histological evaluation of neuronal damage was carried out using the silver
      staining technique in gerbils 4 and 21 days after the start of the experimental
      protocol. Behavioral functions were assessed in gerbils from the 14th to the 21st
      day after the start of the experimental protocol using the Morris water maze
      test. Results obtained from this study showed no significant difference between
      saline treated TMZ-treated gerbils when TMZ was administered after ischemia. When
      TMZ was administered prior to ischemia, there was a reduction in neuronal damage
      although it did not reach statistical significance and a statistically
      significant improvement in behavior. We conclude that TMZ shows signs of promise
      as a neuroprotective agent, and further studies should look at pre-treatment with
      different doses and different times.

PMID- 11844467
TI  - Molecular probes of the vestibular nerve. I. Peripheral termination patterns of
      calretinin, calbindin and peripherin containing fibers.
AB  - Vestibular afferents have different physiological properties that can be at least
      partially correlated with the morphology that the peripheral ending makes with
      type I and type II hair cells. If the location of the ending in the sensory
      epithelium is included, the correlations are further improved. It is also known
      that vestibular afferents can be immunohistochemically stained for a variety of
      different substances. We have concentrated on three of these markers, calretinin,
      calbindin and peripherin, because the sources of afferents to the vestibular
      nuclear complex that contain these substances are restricted, in two cases to the
      primary afferents. We demonstrate that calretinin is found only in the calyx-only
      afferents that are located at the apex of the cristae ampullaris and along the
      striola of the maculae. The area containing stained calyces is equal to or
      slightly smaller than the central zone of the cristae as defined by the Goldberg
      group [J. Neurophysiol. 60 (1988) 167]. Calbindin is also found in calyces at the
      apex of the cristae and along the striola of the otoliths. Examination of
      adjacent sections of all endorgans indicates that calbindin staining overlaps
      with calretinin, but is always several hair cells wider on each side. Peripherin
      also stains fibers in the neuroepithelium. The greatest density of staining is in
      the peripheral zone of the cristae, i.e. at the base and toward the planum
      semilunatum. We suggest that these substances are useful markers for specific
      sets of vestibular afferents.

PMID- 11844468
TI  - Molecular probes of the vestibular nerve. II. Characterization of neurons in
      Scarpa's ganglion to determine separate populations within the nerve.
AB  - An unambiguous delineation of the exact numbers and/or proportions of calyx-only,
      dimorph, and bouton-only vestibular afferents is needed to continue studies
      concerning vestibular integration in the nervous system. Here, we take advantage
      of immunocytochemical properties of three groups of vestibular afferents. We
      utilize calretinin to delineate the calyx-only population, and peripherin to
      stain the bouton-only afferents. An additional subgroup of afferents that stain
      with calbindin, but not calretinin is also introduced. The size of the cells that
      stain with these markers was determined. Cells that are calbindin-positive
      overlap the sizes of Nissl-stained somata. Cells that stain with peripherin or
      calretinin are non-overlapping with calretinin cells being the largest and
      peripherin-positive cells the smallest. Twenty percent of the ganglion cells were
      peripherin positive, another 20% stained with calretinin antibodies, 30% stained
      with calbindin, and all cells in Scarpa's ganglion stained with parvalbumin. Most
      of the calretinin-positive cells also stained with calbindin. One-third of the
      calbindin-positive population stained only with calbindin. These studies indicate
      that the calyx- and bouton-only populations of vestibular afferents in gerbil
      comprise at least 40% of the nerve. In addition, at least 10% of the nerve also
      stains with calbindin and neither calretinin nor peripherin. Based on indirect
      evidence, we hypothesize that these are a subpopulation of dimorph afferents.
      This study has provided an anatomical instrument (in addition to intracellular
      physiological methods) to study separate populations of vestibular afferents.

PMID- 11844469
TI  - Intermittent, chronic fenfluramine administration to rats repeatedly suppresses
      food intake despite substantial brain serotonin reductions.
AB  - The mechanisms by which fenfluramine suppresses food intake and body weight have
      been linked to its ability to enhance transmission across serotonin synapses in
      brain. This drug initially lowers body weight and suppresses food intake, yet
      after repeated administration food intake soon returns to normal and body weight
      no longer decreases. Fenfluramine also causes rapid and prolonged reductions in
      brain serotonin concentrations, which might account for its loss of appetite
      suppression. This possibility has been evaluated in rats by assessing if
      intermittent, chronic fenfluramine administration could suppress food intake
      during each treatment period, and if so, whether such an effect occurs in the
      presence of reduced brain serotonin levels. Rats were injected once daily with 10
      mg/kg D,L-fenfluramine for 5 days, and then received no injections for the next 5
      days. Control rats received only vehicle injections. This 10-day sequence was
      repeated five more times. During each period of fenfluramine administration,
      daily food intake dropped markedly the first 1-2 days of treatment, but returned
      to pretreatment values by day 5. Daily food intake was normal or slightly above
      normal during non-injection periods. Body weight dropped modestly during each
      period of fenfluramine administration, and rose during each subsequent period
      when injections had ceased. Serotonin concentrations and synthesis rates in
      several brain regions were markedly reduced at early, middle, and late periods of
      the experiment. Despite the long-term reduction in brain serotonin pools produced
      by fenfluramine, the drug continues to reduce food intake and body weight.
      Several possible interpretations of these findings are considered, based on the
      multiple mechanisms through which this drug has been proposed to modify synaptic
      serotonin transmission.

PMID- 11844471
TI  - Anxiolytic-like effect of way-100635 microinfusions into the median (but not
      dorsal) raphe nucleus in mice exposed to the plus-maze: influence of prior test
      experience.
AB  - Studies in several laboratories have confirmed the anxiolytic potential of a wide
      range of 5-HT(1A) receptor antagonists in rats and mice, with recent evidence
      pointing to a postsynaptic site of action in the ventral hippocampus. It would,
      therefore, be predicted that blockade of 5-HT(1A) somatodendritic autoreceptors
      in the midbrain raphe nuclei should produce anxiogenic-like effects. To test this
      hypothesis, we investigated the effects of WAY-100635 microinfusions (0, 1.0 or
      3.0 microg in 0.1 microl) into the dorsal (DRN) or median (MRN) raphe nuclei on
      behaviours displayed by male Swiss-Webster mice in the elevated plus-maze. As
      this test is sensitive to prior experience, the effects of intra-raphe infusions
      were examined both in maze-naive and maze-experienced subjects. Sessions were
      videotaped and subsequently scored for conventional indices of anxiety (open arm
      avoidance) and locomotor activity (closed arm entries), as well as a range of
      ethological measures (e.g. risk assessment). In maze-naive mice, intra-MRN (but
      not intra-DRN) infusions of WAY-100635 (3.0 microg) increased open arm
      exploration and reduced risk assessment. Importantly, these effects could not be
      attributed to a general reduction in locomotor activity. A similar, though
      somewhat weaker, pattern of behavioural change was observed in maze-experienced
      animals. This unexpected anxiolytic effect of 5-HT(1A) autoreceptor blockade in
      the MRN cannot be accounted for by a disinhibition of 5-HT release in forebrain
      targets (e.g. hippocampus and amygdala), where stimulation of postsynaptic 5
      HT(1A) receptors enhances anxiety-like responses. However, as the MRN also
      projects to the periaqueductal gray matter (PAG), an area known to be sensitive
      to the anti-aversive effects of 5-HT, it is argued that present results may
      reflect increased 5-HT release at this crucial midbrain locus within the neural
      circuitry of defense.

PMID- 11844470
TI  - Role of endothelium in hyperemia during cortical spreading depression (CSD) in
      the rat.
AB  - The purpose of this study was to examine whether endothelium-mediated dilation is
      responsible for the cortical hyperemia that occurs during cortical spreading
      depression (CSD) in rats using three different approaches. The first approach
      taken was the acute pharmacological inhibition of the predominant endothelium
      centered dilator systems, using indomethacin, a cyclooxygenase inhibitor, Nomega
      nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase (NOS) inhibitor,
      and miconazole, a cytochrome P-450 epoxygenase inhibitor. The second approach
      used was the acute general pharmacological impairment of endothelial function by
      the intravascular administration of phorbol 12, 13-dibutyrate (PDBu). The third
      approach taken was the chronic impairment of endothelium-dependent dilator
      responses by diet in insulin resistant (IR) rats. Cerebral blood flow (CBF) was
      measured using laser Doppler flowmetry. CSD was elicited by the topical
      application of potassium chloride. Pharmacological inhibition of endothelium
      dependent dilator factors did not affect CSD. For example, with 20 mg/kg L-NAME,
      CBF peak of the first series of CSDs was 377 +/- 67% of baseline CBF. After drug
      administration, CBF peaks of the second and the third series of CSDs were 451 +/-
      67% and 390 +/- 69% (n=5, P=n.s.), respectively. Control and IR animals and those
      treated with indomethacin, miconazole and PDBu showed similar results. We also
      calculated the area under the CBF curve to fully represent the extent of
      hyperemia during CSD. However, there were no significant differences in the CBF
      area with any treatment compared to control animals. Thus, our results provide
      strong evidence that endothelium-mediated mechanisms have minimal effects on the
      CSD-associated hyperemia.

PMID- 11844472
TI  - Hippocampal lesions, contextual retrieval, and autoshaping in pigeons.
AB  - Both pigeons and rats with damage to the hippocampus are slow to acquire an
      autoshaped response and emit fewer overall responses than control animals.
      Experiment 1 explored the possibility that the autoshaping deficit was due to an
      impairment in contextual retrieval. Pigeons were trained for 14 days on an
      autoshaping task in which a red stimulus was followed by reinforcement in context
      A, and a green stimulus was followed by reinforcement in context B. On day 15,
      the subjects were given a context test in which the red and green stimuli were
      presented simultaneously in context A and then later in context B. Both control
      and hippocampal animals showed context specificity, that is, they responded more
      to the red stimulus in context A and to the green stimulus in context B. In
      Experiment 2 we video-recorded the control and hippocampal animals performing the
      autoshaping task. Hippocampal animals tended to miss-peck the key more often than
      control animals. In addition, the number of missed pecks increased across days
      for hippocampal animals but not for control animals, suggesting that while the
      control animals increased their pecking accuracy, the hippocampal animals
      actually decreased their pecking accuracy. Our findings suggest that impairments
      in moving through space may underlie the hippocampal autoshaping deficit.

PMID- 11844473
TI  - Evaluation of preconditioning treatments to protect near-pure cortical neuronal
      cultures from in vitro ischemia induced acute and delayed neuronal death.
AB  - We evaluated the efficacy of cycloheximide, heat stress, NMDA receptor blockade
      (MK801/AP-5), oxygen--glucose deprivation, hypoxia, hypothermia and TNFalpha
      preconditioning to protect cortical neurons from in vitro ischemic insults that
      result in acute necrotic and delayed apoptotic neuronal death. Preconditioning
      treatments were performed 22--24 h before in vitro ischemia. In vitro ischemia
      was carried out in 96-well microtitre strip-plates by washing neuronal cultures
      with a balanced salt solution containing 25 mM 2-deoxy-D-glucose and incubating
      in an anaerobic chamber. Glutamate receptor blockers were present during in vitro
      ischemia to induce delayed neuronal death. Cycloheximide, heat stress, MK801 and
      oxygen--glucose deprivation preconditioning were neuroprotective in both acute
      and delayed in vitro ischemic neuronal death models. AP-5 preconditioning and a
      12 h post-MK801 preconditioning interval protected neurons from acute ischemic
      neuronal death only. Hypoxia, TNFalpha and hypothermic preconditioning provided
      no neuronal protection in the in vitro ischemia models. This study has confirmed
      for the first time that several preconditioning treatments can protect neurons
      from in vitro ischemia induced acute necrotic and delayed apoptotic neuronal
      death. In addition, a unique feature of this study is the finding that
      preconditioning could be induced in near-pure primary cortical neuronal cultures,
      thus confirming that ischemic tolerance is an intrinsic property of neurons and
      provides a simplified culture system for identifying neuroprotective proteins.

PMID- 11844474
TI  - Relationship between beta-AP peptide aggregation and microglial activation.
AB  - We compared the relationship between the state of aggregation of two peptides
      (beta-AP 25-35 and beta-AP 1-42) and microglial activation. After 7 days at 37
      degrees C beta-AP 25-35 was in an amorphous state and did not activate microglial
      cells. In the same conditions, aggregated beta-AP 1-42 activated these cells and
      caused changes in microglial ramification, increasing the proliferation index and
      inducing tumor necrosis factor alpha (TNF alpha) release. Neither peptide induced
      a release of nitric oxide (NO). As the toxicity of beta-AP peptides in cell
      culture is associated with the formation of amyloid fibrils, we also examined the
      toxicity of both peptides in microglial cell cultures and in PC 12 cell cultures.
      The results suggest that the two beta-AP fragments studied have similar
      neurotoxic effects but different pro-inflammatory activities.

PMID- 11844475
TI  - Perinatal choline treatment modifies the effects of a visuo-spatial attractive
      cue upon spatial memory in naive adult rats.
AB  - The improvement in memory functions by choline supplementation is hypothesized to
      be due to increased synthesis and release of acetylcholine in the brain. We have
      found previously that combined pre- and postnatal choline supplementation results
      in long-lasting facilitation of spatial memory in juvenile rats when training was
      conducted in presence of a local salient cue. The present work aims to analyze
      the effects of peri- and postnatal choline supplementation on spatial abilities
      of naive adult rats. Treated rats were trained in various cued procedures of the
      Morris navigation task of 5 months of age. The treatment had a specific effect of
      reducing the escape latency of the rats when the platform was at a fixed location
      in space and indicated by a suspended cue. This effect was associated with an
      improved spatial memory when the cue and the platform were removed. In this
      condition, the control rats showed impaired spatial discrimination following the
      removal of the target cue, most likely due to an overshadowing of the distant
      environmental cues. This impairment was not observed in the treated rats. Further
      training with the suspended cue at unpredictable places in the pool revealed
      longer escape latencies in the control than in the treated rats suggesting that
      this procedure induced a selective perturbation of the normal but not of the
      treated rats. A special probe trial with the cue at an irrelevant location and no
      escape platform revealed a significant bias of the control rats towards the cue,
      but in treated rats towards the uncued spatial escape position. This behavioral
      dissociation suggests that a salient cue associated with the target induces an
      alternative "non spatial" guidance strategy in normal rats, with the risk of
      overshadowing attention towards more distant spatial cues. As a consequence, the
      improved escape in the presence of the cue in the treated rats is associated with
      a stronger memory of the spatial position following disappearance of the cue.
      This and previous observations suggest that a specific spatial attentional
      process relies on the buffering of highly salient visual cues to facilitate
      integration of their relative position in the environment.

PMID- 11844476
TI  - Apolipoprotein E4 inhibits, and apolipoprotein E3 promotes neurite outgrowth in
      cultured adult mouse cortical neurons through the low-density lipoprotein
      receptor-related protein.
AB  - The apolipoprotein E4 (apoE4) genotype is a major risk factor for Alzheimer's
      disease (AD); however, the mechanism is unknown. We previously demonstrated that
      apoE isoforms differentially modulated neurite outgrowth in embryonic neurons and
      in neuronal cell lines. ApoE3 increased neurite outgrowth whereas apoE4 decreased
      outgrowth, suggesting that apoE4 may directly affect neurons in the brain. In the
      present study we examined the effects of apoE on neurite outgrowth from cultured
      adult mouse cortical neurons to examine if adult neurons respond the same way
      that embryonic cells do. The results from this study demonstrated that (1)
      cortical neurons derived from adult apoE-gene knockout (apoE KO) mice have
      significantly shorter neurites than neurons from adult wild-type (WT) mice; (2)
      incubation of cortical neurons from adult apoE KO mice with human apoE3 increased
      neurite outgrowth, whereas human apoE4 decreased outgrowth in a dose-dependent
      fashion; (3) the isoform specific effects were abolished by incubation of the
      neurons with either receptor associated protein (RAP) or lactoferrin, both of
      which block the interaction of apoE-containing lipoproteins with the low-density
      lipoprotein receptor-related protein (LRP). These data suggest a potential
      mechanism whereby apoE4 may play a role in regenerative failure and accelerate
      the development of AD.

PMID- 11844477
TI  - Guanine based purines inhibit [(3)H]glutamate and [(3)H]AMPA binding at
      postsynaptic densities from cerebral cortex of rats.
AB  - Extracellular guanine-based purines (GBPs) have been implicated in
      neuroprotective effects against glutamate toxicity by modulating the
      glutamatergic system through mechanisms without the involvement of G proteins.
      Accordingly, GBPs have been shown to inhibit the binding of glutamate and its
      analogs in different brain membrane preparations. However, brain membrane
      preparations used for these studies are comprised of both post- and pre-neuronal
      and glial synaptic components. In this study we investigated the ability of GBPs
      to displaced glutamate and AMPA binding at postsynaptic densities (PSDs). PSDs
      are markedly prominent in glutamatergic synapses and retains the native
      apposition of membrane components and post synaptic receptors. The PSD fraction
      was prepared from cerebral cortex of Wistar rats and it was characterized as PSDs
      by electron microscopy and by an enrichment of PSD-95, a protein marker of PSDs
      (90% of immunodetection). Moreover, we detected an enrichment of glutamate
      receptors subunits that including NR1 subunit of NMDA receptors and GluR1 subunit
      of AMPA receptors. GppNp (poor hydrolyzable GTP analog) and GMP displaced 40 and
      36% of glutamate binding, respectively, and guanosine only 23%. AMPA binding was
      not affected by guanosine and was inhibited 21 and 25% by GppNp and GMP,
      respectively. Hence, this study demonstrates that guanine based purines inhibited
      glutamate and AMPA binding at postsynaptic membrane preparations, contributing
      for a better understanding of the mechanisms by which GBPs antagonize
      glutamatergic neurotoxicicity, e.g. the possible involvement of glutamatergic
      postsynaptic receptors in their neuroprotective roles.

PMID- 11844479
TI  - Age-independent and age-related deficits in visuospatial learning, sleep-wake
      states, thermoregulation and motor activity in PDAPP mice.
AB  - Recent studies demonstrated that mice overexpressing the human mutant beta
      amyloid precursor protein (hbetaAPP; PDAPP mice) show age-independent and age
      related deficits in spatial learning. We used behavioral and electrophysiological
      techniques to determine in young and aged PDAPP mice whether deficits in spatial
      learning also involve alterations in sleep-wake states, thermoregulation and
      motor activity. Consistent with earlier studies, young PDAPP mice exhibited
      selective age-independent deficits using spatial, but not random and serial
      strategies in the circular maze. Aged PDAPP mice exhibited deficits using all
      search strategies. The core body temperature (Tb) in young and aged PDAPP mice
      was significantly lower than in age-matched non-transgenic (non-Tg) littermates.
      During the dark period, the motor activity (LMA) was significantly increased in
      young PDAPP mice, but not in aged PDAPP mice. During the light period, young
      PDAPP mice showed a reduction in the generation of rapid-eye-movement (REM)
      sleep. In contrast, aged PDAPP mice exhibited a reduction in the amount of time
      spent in W and an increase in SWS during the light period. Aged PDAPP mice also
      showed an increase in the amount of time spent in W and a reduction in REM sleep
      during the dark period. Our findings support previous reports indicating deficits
      in spatial learning in young and aged PDAPP mice. These data also suggest that
      PDAPP mice exhibit age-independent and age-related deficits in neural mechanisms
      regulating visuospatial learning, the total amount and the circadian distribution
      of sleep-wake states, thermoregulation and motor activity.

PMID- 11844480
TI  - Immunohistochemical localization of GDNF in the human hippocampal formation from
      prenatal life to adulthood.
AB  - In this study, we examined the immunohistochemical occurrence and distribution of
      glial cell line-derived neurotrophic factor (GDNF) in autoptic specimens of
      normal human hippocampus at different ages, from 22 weeks of gestation (w.g.) to
      adult life. Two different anti-GDNF polyclonal antibodies were used. Western blot
      analysis on homogenates of human and rat brain and recombinant human GDNF
      resulted in differential detection of monomeric and dimeric forms of the
      proteins. The ABC immunohistochemical technique revealed that in the Ammon's
      horn, numerous positive cell bodies occurred in the pyramidal layer, the majority
      of them being present in the proximal CA1 and in CA2. Sparse positive neurons
      could be observed in the stratum oriens and moleculare. In the fascia dentata
      many granule cells showed a light punctate staining, whereas more heavily
      labelled neurons occurred in the polymorphic layer and, occasionally, in the
      molecular layer. The distribution pattern of GDNF-like immunoreactivity appeared
      consistently similar throughout life stages from 29 w.g. to adult age. However,
      intensity of labelling and frequency of neuronal cell bodies was highest in the
      neonate and decreased in adulthood. The present data provide a comprehensive map
      of the localization of GDNF-like immunoreactive neurons in the human archicortex
      at developmental ages and in the mature tissue and represent a first step towards
      the identification of hippocampal neurons which express the protein and/or are
      responsive to it. They further suggest that GDNF may play a role in the
      development of intrahippocampal circuitry and in neuronal function and
      maintenance throughout life.

PMID- 11844478
TI  - Chemical stimulation of the dorsomedial hypothalamus evokes non-shivering
      thermogenesis in anesthetized rats.
AB  - Disinhibition of neurons in the dorsomedial hypothalamus (DMH) by microinjection
      of the GABA(A) receptor antagonist bicuculline methiodide (BMI) elicits a range
      of autonomic and endocrine changes resembling those seen in experimental
      paradigms for emotional stress. Stress in rats is also known to provoke increases
      in body temperature resulting in part from sympathetically mediated activation of
      brown fat. The purpose of the present study was to examine the effect of
      microinjection of BMI into the DMH on core body temperature and temperature of
      brown fat in rats. In anesthetized preparations, microinjection of BMI 10 pmol/50
      nl into the DMH and adjoining posterior hypothalamus elicited marked and rapid
      increases in temperature in interscapular brown adipose tissue (IBAT) and lesser
      delayed elevations in rectal temperature. Similar injections into the
      paraventricular nucleus or ventromedial hypothalamus had no effect on either
      parameter. Peak increases in IBAT were significantly correlated with both peak
      increases in core temperature and maximal increases in heart rate that
      accompanied these changes, and all of these effects were abolished by systemic
      treatment with propranolol 1 mg/kg. In conscious rats instrumented for telemetry,
      microinjection of BMI 10 pmol/100 nl into the DMH evoked marked increases in core
      temperature as well as heart rate, locomotor activity, and plasma ACTH. The
      increase in core temperature occurred with a delayed time course similar to that
      seen in anesthetized preparations. These results indicate that activation of
      neurons in the DMH provokes increases in body temperature resulting in large part
      from sympathoadrenally-mediated activation of brown fat.

PMID- 11844481
TI  - cDNA cloning, chromosomal localization and expression pattern analysis of human
      LIM-homeobox gene LHX4.
AB  - LHX4 gene is a member of the LIM-homeobox gene family and plays a critical role
      in the development of motor neurons. We have isolated a cDNA of human LHX4 from a
      library of the adult human spinal cord. Its sequence is 92% homologous to that of
      the mouse Lhx4. The genomic structure of the LHX4 gene and its chromosomal
      localization were determined. The gene was mapped on human chromosome 1q 24.1-1q
      24.3 and composed of six exons. The homeodomain was encoded by two exons, exons 4
      and 5. The first LIM domain was coded by exon 2, and the second by exon 3. Human
      MTE Array was used to study the expression profile of LHX4 in 72 human tissues.
      The expression was specific in the CNS including the fetal brain, the spinal
      cord, and the cerebral cortex. In situ hybridization of the adult rodent CNS
      showed the abundant expression of LHX4 in the cerebral cortex and motor neurons
      of the spinal cord. Our results suggest that LHX4 may play a role in the CNS,
      especially the neocortex and the spinal cord, and provide a basis to investigate
      potential involvement of the LHX4 gene in human diseases.

PMID- 11844482
TI  - Lactate administration attenuates cognitive deficits following traumatic brain
      injury.
AB  - Moderately head injured patients often suffer long term neurological sequelae.
      There is no therapy for brain trauma and current treatments aim only to minimize
      secondary damage. These secondary effects are often triggered by the inability to
      re-establish ionic homeostasis after injury, due to large energy demands. Recent
      reports have demonstrated that neurons are capable of utilizing lactate as an
      energy source, thus this report examines the usefulness of lactate administration
      in the attenuation of behavioural deficits following a moderate brain injury.
      Lactate infusion (i.v.) was started 30 min after lateral fluid percussion injury
      and continued for 3 h. Cognitive deficits were determined using the Morris water
      maze. Lactate infused injured animals demonstrated significantly less cognitive
      deficits than saline infused injured animals. Thus, lactate infusion attenuated
      the cognitive deficits normally observed in this model, and therefore may provide
      moderately head injured patients with a treatment to help ameliorate the
      sequelae.

PMID- 11844483
TI  - Expression of glial cell line-derived neurotrophic factor mRNA in the human
      newborn and adult hippocampal formation.
AB  - Glial cell line-derived neurotrophic factor (GDNF) mRNA-containing neurons were
      found in normal neonate and adult human hippocampus with a localization pattern
      consistently similar among different ages. They were numerous in proximal CA1 to
      CA3 pyramidal layer, granular layer and hilus, and sparse in oriens and molecular
      layers. The present data provide a map of GDNF-producing neurons in the human
      archicortex and suggest a role for GDNF in neuronal function throughout life.

PMID- 11844484
TI  - Localization of zinc-enriched neurons in the mouse peripheral sympathetic system.
AB  - Growing evidence supports the notion that zinc ions located in the synaptic
      vesicles of zinc-enriched neurons (ZEN) play important physiological roles and
      are involved in certain pathological changes in the central nervous system. Here
      we present data revealing the distribution of zinc ions and the co-localization
      of zinc transporter 3 (ZnT3) and tyrosine hydroxylase (TH) in crush-operated
      sciatic nerves and lumbar sympathetic ganglia of mice, using zinc selenide
      autometallography (ZnSe(AMG)) and ZnT3 immunofluorescence combined with confocal
      scanning microscopy, respectively. Six hours after the crush operation, ZnSe(AMG)
      grains and ZnT3 immunoreactivity were predominantly present in a subpopulation of
      thin unmyelinated sciatic nerve axons. In order to identify the type(s) of ZEN
      axons involved, double labeling with ZnT3 and (1) TH, (2) vesicular acetylcholine
      transporter (VAChT), (3) calcitonin gene-related peptide (CGRP), and (4)
      neuropeptide Y (NPY) was performed. Confocal microscopic observations showed that
      ZnT3 was located in a subpopulation of sciatic axons in distended parts proximal
      and distal to the crush site. Most, if not all, ZnT3-positive axons contained TH
      immunofluorescence, a few showed co-localization of ZnT3 and VAChT with very weak
      immunostaining, while no congruence was observed between ZnT3 and CGRP or NPY.
      Studies of the lumbar sympathetic ganglia showed that not more than 5% of the
      neurons were ZnT3-positive and that almost all of these were TH-positive.
      Furthermore, approximately 5% of total lumbar sympathetic ganglionic cells were
      ZnSe(AMG) positive, 48 h after a local injection of sodium selenide into the
      sciatic nerve. The present data support the notion that a subgroup of mouse
      sympathetic postganglionic neurons are ZEN neurons.

PMID- 11844485
TI  - Age-related changes in GluR2 and NMDAR1 glutamate receptor subunit protein
      immunoreactivity in corticocortically projecting neurons in macaque and patas
      monkeys.
AB  - A distinct subpopulation of neurons forming long corticocortical projections in
      the association neocortex is highly vulnerable to the degenerative process in
      Alzheimer's disease. However, the degree to which age-related molecular and
      morphologic alterations of identifiable neuronal populations reflects early
      cellular degeneration leading to functional deficits has not yet been fully
      investigated in the aging brain. We performed an immunohistochemical analysis of
      neurons forming short and long corticocortical projections in young and old
      monkeys using antibodies to the GluR2 and NMDAR1 glutamate receptor subunit
      proteins. Projection neurons differed in their expression of these receptor
      subunits, as GluR2 was less prevalent than NMDAR1 among retrogradely labeled
      neurons. Long and short corticocortical pathways in old animals demonstrated a
      considerable decrease in the proportions of projection neurons containing GluR2
      and NMDAR1, an observation that was particularly consistent in the case of GluR2.
      No age-related differences were observed in distribution of neurofilament protein
      in either type of projection neurons. These data suggest that cortical neurons
      furnishing long and short corticocortical projections display consistent
      neurochemical changes during aging and that a differential decrease in cellular
      expression of glutamate receptor subunit proteins occurs. The fact that in aging
      these neurons have lower levels of GluR2 than in young individuals, but
      comparatively higher levels of NMDAR1 than GluR2, may render them prone to
      calcium-mediated excitotoxicity, which in humans may be related to the selective
      vulnerability of such neurons during the course of Alzheimer's disease. Also, it
      is apparent that age-related neuronal changes are quite subtle and involve
      subcellular components of the cortical circuits rather than major morphologic
      alterations.

PMID- 11844486
TI  - Differential induction of p53 in immature and adult rat brain following lithium
      pilocarpine status epilepticus.
AB  - Activation of the tumor suppressor gene, p53, has been strongly implicated in
      selective neuronal cell death. This study investigated p53 expression in the
      immature and adult rat brain following status epilepticus induced by the
      administration of lithium-pilocarpine (LPSE). Both p53 mRNA and protein were
      examined in relation to neuronal degeneration using in situ hybridization and
      immunohistochemistry, respectively. Injured cells with eosinophilic cytoplasm
      with increased p53 mRNA were observed in hippocampal subfields, piriform cortex,
      amygdala and thalamus. p53 mRNA levels reached a peak by 8 h and returned to
      baseline by 24 h after the onset of LPSE. The magnitude of p53 mRNA induction was
      greatest in 21-day-old rats. In contrast to the cellular expression pattern of
      p53 mRNA, immunohistochemistry demonstrated that p53 protein was increased in all
      of the eosinophilic cells. Further, double-labeling studies revealed that p53
      protein was elevated in neurons that were degenerating. This was supported by
      colocalization of activated caspase 3 in some cells with damaged DNA. These
      results provide additional evidence for a critical role for the p53 pathway in
      excitotoxic neuronal cell death due to status epilepticus.

PMID- 11844487
TI  - Mesolimbic dopaminergic system is involved in diurnal blood pressure regulation.
AB  - Parkinson's disease (PD) patients with autonomic failure show no nocturnal
      decrease in blood pressure (BP). At present, it is not clear if this symptom is
      attributable to the disturbance of the dopaminergic (DA) system that is
      responsible for PD. In the present study, we determined that the mesolimbic DA
      system is involved in diurnal profiles of the mean BP (MBP) by destroying the A10
      DA system in rats with 6-hydroxydopamine. In control rats, a clear dip in the MBP
      and heart rate (HR) occurs during the light, that is, resting period, analogous
      to the nocturnal dip in normal humans. This normal daytime decrease in MBP and HR
      was disturbed by inducing a lesion of the ventral tegmental area (VTA) DA
      neurons, although the rhythms of wake-sleep duration and behavioral activity
      remained relatively intact. On the basis of this evidence, the absence of a
      nocturnal dip in BP in PD patients is attributed to impairment of the mesolimbic
      DA system.

PMID- 11844488
TI  - Glycosylamines of 4,6-O-butylidene-alpha-D-glucopyranose: synthesis and
      characterization of glycosylamines, and the crystal structure of 4,6-O-butylidene
      N-(o-chlorophenyl)-beta-D-glucopyranosylamine.
AB  - A total of nine glycosylamines of 4,6-O-butylidene-alpha-D-glucopyranose were
      synthesized using primary amines having various groups in their ortho- or para
      positions. Among these, six are monoglycosylamines, including one primary
      glycosylamine, and three are bis-glycosylamines. All these compounds were
      characterized by 1H, 1H-1H COSY, 1H-13C COSY and 13C NMR spectroscopy and FTIR
      spectra. The FAB mass spectra provided the molecular weights of the products by
      exhibiting the corresponding molecular ion peaks. The crystal structure of 4,6-O
      butylidene-N-(o-chlorophenyl)-beta-D-glucopyranosylamine revealed the C-1
      glycosylation, the beta-anomeric nature, and the 4C1 chair conformation of the
      saccharide unit in the product. In the lattice two types of dimers exist. While
      one type of dimer is formed through O-H...O type of interactions, the other type
      is formed via C-H...O type of interactions. In the direction of these C-H...O
      type of interactions, the dimeric units are connected to form a chain.

PMID- 11844489
TI  - Efficient intramolecular beta-mannoside formation using m-xylylene and
      isophthaloyl derivatives as rigid spacers.
AB  - A series of mannosyl donors linked via position 2 to an m-xylylene or an
      isophthaloyl spacer which was connected to the position 6 of a glucoside acceptor
      afforded, via intramolecular glycosylation, the corresponding disaccharides with
      high beta anomeric ratio.

PMID- 11844490
TI  - A facile regio- and stereoselective synthesis of mannose octasaccharide of the N
      glycan in human CD2 and mannose hexasaccharide antigenic factor 13b.
AB  - A highly concise and effective synthesis of the mannose octasaccharide of the N
      linked glycan in the adhesion domain of human CD2 was achieved via TMSOTf
      promoted selective 6-glycosylation of a trisaccharide 4,6-diol acceptor with a
      pentasaccharide donor, followed by deprotection. The pentasaccharide was
      constructed by selective 3,6-diglycosylation of 1,2-O-ethylidene-beta-D
      mannopyranose with 2-O-acetyl-3,4,6-tri-O-benzoyl-alpha-D-mannopyranosyl-(1-->2)
      3,4,6-tri-O-benzoyl-alpha-D-mannopyranosyl trichloroacetimidate, while the
      trisaccharide was obtained by selective 3-O-glycosylation of allyl 4,6-O
      benzylidene-alpha-D-mannopyranoside with the same disaccharide
      trichloroacetimidate, followed by debenzylidenation. The mannose hexasaccharide
      antigenic factor 13b was synthesized by condensation of a trisaccharide donor, 2
      O-acetyl-3,4,6-tri-O-benzoyl-alpha-D-mannopyranosyl-(1-->2)-3,4,6-tri-O-benzoyl
      alpha-D-mannopyranosyl-(1-->3)-4,6-di-O-acetyl-2-O-benzoyl-alpha-D-mannopyranosyl
      trichloroacetimidate, with a trisaccharide acceptor, methyl 3,4,6-tri-O-benzoyl
      alpha-D-mannopyranosyl-(1-->2)-3,4,6-tri-O-benzoyl-alpha-D-mannopyranosyl-(1-->2)
      3,4,6-tri-O-benzoyl-alpha-D-mannopyranoside, followed by deprotection.

PMID- 11844491
TI  - Improved preparation of perallylated cyclodextrins: facile synthesis of
      cyclodextrin-based polycationic and polyanionic compounds.
AB  - An improved procedure for the perallylation of cyclodextrins allowed the
      preparation of O-perallylated alpha-, beta-, and gamma-cyclodextrins in 89, 91,
      and 88% yields, respectively. These were converted into two cyclodextrin-based
      functionalized compounds, the polycationic heptakis[2,3,6-tri-O-(6-amino-3
      thiahexyl)]-beta-cyclodextrin hydrochloride (3), and the polyanionic
      heptakis[2,3,6-tri-O-(sodium 5-carboxyl-3-thiapentyl)]-beta-cyclodextrin (4), a
      potential inhibitor of HIV-1 replication.

PMID- 11844492
TI  - Alpha-galactosyl fluoride in transfer reactions mediated by the green coffee
      beans alpha-galactosidase in ice.
AB  - We show that the yields in saccharide synthesis by tranglycosylation with alpha
      galactosidase from green coffee beans can be greatly enhanced when working in
      ice. Thus, methyl alpha-D-galactopyranosyl-(1-->3)-alpha-D-galactopyranoside (3a)
      produced by reaction of alpha-D-galactopyranosyl fluoride 1 with methyl alpha-D
      galactopyranoside (2) is obtained with 51% yield in ice while only 29% is
      synthesized at 37 degrees C. This result, already previously found by others with
      proteases and by us with a beta-galactosidase appears to be a general property of
      hydrolases.

PMID- 11844493
TI  - Brown seaweed protein as an inhibitor of marine mollusk endo-(1-->3)-beta-D
      glucanases.
AB  - Aqueous ethanol extracts from brown seaweed were found to contain substances
      inhibiting endo-(1-->3)-beta-D-glucanases, the digestive enzymes of marine
      mollusks. The inhibitors were detected in 70% of the brown seaweeds investigated.
      An irreversible protein inhibitor with high specificity for endo-(1-->3)-beta-D
      glucanases of marine mollusks was isolated from the brown seaweed, Laminaria
      cichorioides. As determined by gel filtration, the molecular weight of the
      inhibitor was 46 kDa. The value of [I]50 (10(-8) M) for the inhibitor was
      comparable with the corresponding value for natural alpha-amylase inhibitors from
      terrestrial plants. Chemical modification results indicated that tryptophan,
      dicarboxylic acid, histidine and probably tyrosine residues of inhibitor molecule
      are important for interaction of the inhibitor with the enzyme.

PMID- 11844494
TI  - Coffee bean arabinogalactans: acidic polymers covalently linked to protein.
AB  - The arabinogalactan content of green coffee beans (Coffea arabica var. Yellow
      Caturra) was released by a combination of chemical extraction and enzymatic
      hydrolysis of the mannan-cellulose component of the wall. Several arabinogalactan
      fractions were isolated, purified by gel-permeation and ion-exchange
      chromatography and characterised by compositional and linkage analysis. The AG
      fractions contained between 6 and 8% glucuronic acid, and gave a positive test
      for the beta-glucosyl-Yariv reagent, a stain specific for arabinogalactan
      proteins. The protein component accounted for between 0.5 and 2.0% of the AGPs
      and contained between 7 and 12% hydroxyproline. The AG moieties displayed
      considerable heterogeneity with regard to their degree of arabinosylation and the
      extent and composition of their side-chains. They possessed a MW average of 650
      kDa which ranged between 150 and 2000 kDa. An investigation of the structural
      features of the major AG fraction, released following enzymatic hydrolysis of the
      mannan-cellulose polymers, allowed a partial structure of coffee arabinogalactan
      to be proposed.

PMID- 11844495
TI  - NMR spectroscopy and chemical studies of an arabinan-rich system from the
      endosperm of the seed of Gleditsia triacanthos.
AB  - Exhaustive extraction of the endosperm from the seed of Gleditsia triacanthos
      using water at room temperature and 50 degrees C left a residue, which was
      further extracted at 95 degrees C. Precipitation of this extract with 2-propanol
      yielded major amounts of galactomannan components, while the supernatant was
      mainly composed of arabinose-rich constituents. Two fractions were obtained by
      anion-exchange chromatography. The fraction that eluted with water is an arabinan
      with (1-->5) alpha-L linkages and branching mainly on C-2, accompanied with equal
      amounts of a low-galactose galactomannan oligosaccharide, and a small proportion
      of a beta-(1-->4)-galactan. The fraction eluted with an increased ionic strength
      consists mainly of a similar arabinan, and lower proportions of a high-galactose
      galactomannan, galactan, and protein. The arabinan moiety in both fractions was
      characterized by chemical analysis and 1D and 2D NMR spectroscopic techniques.

PMID- 11844496
TI  - Acid-catalyzed isomerization of methyl 2-deoxy-D-arabino-hexosides: equilibria,
      kinetics and mechanism.
AB  - Four isomers of methyl 2-deoxy-D-arabino-hexosides were isolated by HPLC as
      chromatographically homogeneous compounds. The rates of pyranoside isomerization
      (alpha(p) and beta(p)) at 40 degrees C and of furanoside isomerization (alpha(f)
      and beta(f)) at 26 degrees C were determined. A mechanism has been suggested for
      transformations taking place during isomerization of methyl 2-deoxy-D-arabino
      hexosides in methanolic solution catalyzed with hydrogen chloride.

PMID- 11844497
TI  - Reinvestigation of the iodocyclization of 4,5,7-tri-O-benzyl-3-(N
      benzylacetamido)-1,2,3-trideoxy-D-gluco-hept-1-enitol: unexpected formation of a
      1,3-imino-heptitol derivative.
AB  - The NIS-mediated iodocyclization of 4,5,7-tri-O-benzyl-3-(N-benzylacetamido)
      1,2,3-trideoxy-D-gluco-hept-1-enitol gave unexpectedly a 1,3-imino-heptitol
      derivative, namely 2-O-acetyl-N-benzyl-4,5,7-tri-O-benzyl-1,3-dideoxy-1,3-imino-D
      glycero-D-ido-heptitol. This compound is a new example of a rare class of
      azetidine imino alditol derivatives which have interesting properties such as
      glycosidase inhibitors. The physical and spectral data for this imino heptitol
      were essentially identical to those reported for 2,6-anhydro-4,5,7-tri-O-benzyl-3
      (N-benzylacetamido)-3-deoxy-D-glycero-D-ido-heptitol, a derivative of C-(2
      acetamido-2-deoxy-alpha-D-glucopyranosyl)methanol obtained from the same
      precursor [Lay, L.; Nicotra, F.; Panza, L.; Verani, A. Gazz. Chim. Ital. 1992,
      122, 345-348]; these findings cast doubts on the structure reported for the
      latter product.

PMID- 11844498
TI  - Complete 1H and 13C spectral assignment of floridoside.
AB  - Floridoside (2-O-alpha-D-galactopyranosylglycerol) was extracted from the red
      marine alga Rhodymenia palmata, and purified by ion-exchange chromatography: 1D
      and 2D NMR spectroscopy experiments were used to unambiguously assign the
      complete 1H and 13C spectra.

PMID- 11844499
TI  - Thermodynamic insight into the origin of the inclusion of monosulfonated isomers
      of triphenylphosphine into the beta-cyclodextrin cavity.
AB  - Formation of inclusion complexes between the beta-cyclodextrin and the potassium
      salt of o-, m-, and p-substituted monosulfonated triphenylphosphine derivatives
      was investigated in aqueous solution by NMR spectroscopy. Titration and
      continuous variation plots obtained from 31P and 1H NMR data indicate the
      formation of a 1:1 inclusion complex for the three phosphine isomers. T-ROESY NMR
      experiments show that in all cases a non-sulfonated aromatic ring was included
      into the hydrophobic cavity of beta-cyclodextrin from the secondary hydroxyl
      groups side. The standard enthalpy and entropy of the inclusion process were
      estimated from the temperature dependence of the association constant. All
      inclusion complexes were enthalpy stabilized, but highly entropy destabilized.

PMID- 11844501
TI  - Debate provides cautious optimism for global health.

PMID- 11844502
TI  - Impact of surgical innovation on liver transplantation.

PMID- 11844503
TI  - Lessons for US postpartum care.

PMID- 11844504
TI  - Coronary reperfusion: numerators searching for denominators.

PMID- 11844505
TI  - Doing justice--justly.

PMID- 11844506
TI  - Practice variation and missed opportunities for reperfusion in ST-segment
      elevation myocardial infarction: findings from the Global Registry of Acute
      Coronary Events (GRACE).
AB  - BACKGROUND: The benefits of reperfusion therapy for patients with acute coronary
      syndromes have been established, but there is much variation in the type of
      reperfusion given and decisions about which patients are eligible. This study
      assessed current practices in relation to reperfusion therapy of ST-segment
      elevation myocardial infarction from data collected in the multinational,
      prospective Global Registry of Acute Coronary Events. METHODS: 94 hospitals in 14
      countries are recruiting patients for the registry. Hospitals are organised into
      population-based clusters that reflect the population characteristics of the
      region. Information about patients' demographic characteristics, presenting
      symptoms, medical history, time between symptom onset and presentation, and
      clinical and electrocardiographic features is recorded in a standard case record.
      FINDINGS: Of the 9251 patients enrolled, 1763 presented within 12 h of symptom
      onset with ST-segment-elevation myocardial infarction. Of these, 30% did not
      receive reperfusion therapy. Elderly patients (75 years and older), those
      presenting without chest pain, and those with a history of diabetes, congestive
      heart failure, myocardial infarction, or coronary bypass surgery were less likely
      to receive reperfusion therapy. The rate of primary percutaneous coronary
      intervention was highest in the USA and lowest in Australia, New Zealand, and
      Canada. The rate at sites with a catheterisation laboratory was 19% compared with
      zero at sites without this facility. INTERPRETATION: A substantial proportion of
      patients who are eligible for reperfusion therapy still do not receive this
      treatment. These typically high-risk patients can be identified in advance, and
      reasons for the underuse of these beneficial treatments need to be clarified.

PMID- 11844507
TI  - Effects of redesigned community postnatal care on womens' health 4 months after
      birth: a cluster randomised controlled trial.
AB  - BACKGROUND: Much postpartum physical and psychological morbidity is not addressed
      by present care, which tends to focus on routine examinations. We undertook a
      cluster randomised controlled trial to assess community postnatal care that has
      been redesigned to identify and manage individual needs. METHODS: We randomly
      allocated 36 general practice clusters from the West Midlands health region of
      the UK to intervention (n=17) or control (19) care. Midwives from the practices
      recruited women and provided care. 1087 (53%) of 2064 women were in practices
      randomly assigned to the intervention group, with 977 (47%) women in practices
      assigned to the control group. Care was led by midwives, with no routine contact
      with general practitioners, and was extended to 3 months. Midwives used symptom
      checklists and the Edinburgh postnatal depression scale (EPDS) to identify health
      needs and guidelines for the management of these needs. Primary outcomes at 4
      months were obtained by postal questionnaire and included the women's short form
      36 physical (PCS) and mental (MCS) component summary scores and the EPDS.
      Secondary outcomes were women's views about care. Multilevel analysis accounted
      for possible cluster effects. FINDINGS: 801 (77%) of 1087 women in the
      intervention group and 702 (76%) of 977 controls responded at 4 months. Women's
      mental health measures were significantly better in the intervention group (MCS,
      3.03 [95% CI 1.53-4.52]; EPDS -1.92 [-2.55 to -1.29]; EPDS 13+ odds ratio 0.57
      [0.43-0.76]) than in controls, but the physical health score did not differ.
      INTERPRETATION: Redesign of care so that it is midwife-led, flexible, and
      tailored to needs, could help to improve women's mental health and reduce
      probable depression at 4 months' postpartum.

PMID- 11844508
TI  - Asthma in exercising children exposed to ozone: a cohort study.
AB  - BACKGROUND: Little is known about the effect of exposure to air pollution during
      exercise or time spent outdoors on the development of asthma. We investigated the
      relation between newly-diagnosed asthma and team sports in a cohort of children
      exposed to different concentrations and mixtures of air pollutants. METHODS: 3535
      children with no history of asthma were recruited from schools in 12 communities
      in southern California and were followed up for up to 5 years. 265 children
      reported a new diagnosis of asthma during follow-up. We assessed risk of asthma
      in children playing team sports at study entry in six communities with high
      daytime ozone concentrations, six with lower concentrations, and in communities
      with high or low concentrations of nitrogen dioxide, particulate matter, and
      inorganic-acid vapour. FINDINGS: In communities with high ozone concentrations,
      the relative risk of developing asthma in children playing three or more sports
      was 3.3 (95% CI 1.9-5.8), compared with children playing no sports. Sports had no
      effect in areas of low ozone concentration (0.8, 0.4-1.6). Time spent outside was
      associated with a higher incidence of asthma in areas of high ozone (1.4, 1.0
      2.1), but not in areas of low ozone. Exposure to pollutants other than ozone did
      not alter the effect of team sports. INTERPRETATION: Incidence of new diagnoses
      of asthma is associated with heavy exercise in communities with high
      concentrations of ozone, thus, air pollution and outdoor exercise could
      contribute to the development of asthma in children.

PMID- 11844509
TI  - Laparoscopic living donor hepatectomy for liver transplantation in children.
AB  - BACKGROUND: Because cadaveric organ donors are in short supply, living donors are
      increasingly being used in transplantations. We have developed a safe and
      reproducible method for laparoscopic liver resection. METHODS: Left hepatic
      lobectomy (resection of segments 2 and 3) was done by laparoscopy in one woman
      aged 27 years and one man aged 31 years. The grafts were prepared under
      laparoscopy, without any vascular clamping, and were externalised through a
      suprapubic Pfannenstiel incision. Both grafts were transplanted conventionally to
      the patients' respective sons, who were both aged 1 year and had biliary atresia.
      FINDINGS: Donor operations lasted 7 h for the woman and 6 h for the man, and warm
      ischaemia times were 4 and 10 min, respectively. Blood loss was 150 and 450 mL,
      respectively, and no transfusions were required. Neither patient had
      complications during or after surgery; and hospital stay was 7 and 5 days,
      respectively. Both recipients are alive and have excellent graft function.
      INTERPRETATION: We have shown the feasibility of laparoscopic living donor
      hepatectomy from parent to child. If the safety and feasibility of this procedure
      can be shown in larger series, laparoscopic donor left lobectomy could become a
      new option for paediatric living donor liver transplantation.

PMID- 11844510
TI  - Cystic lesion of the posterior fossa.

PMID- 11844511
TI  - Association between functional polymorphism in EGF gene and malignant melanoma.
AB  - BACKGROUND: Malignant melanoma, the most serious cutaneous malignancy, has
      attracted substantial attention because of its rapidly increasing incidence and
      the poor prognosis of some tumours. Little is known of the genetic factors that
      mediate susceptibility to, and outcome of, sporadic malignant melanoma. Because
      of its role in mitogenesis, which is especially relevant to wound healing,
      tumorigenesis, and proliferation of epidermal tissues, epidermal growth factor
      (EGF) is an attractive candidate in which to look for genetic polymorphisms.
      METHODS: We enrolled 135 white European patients with malignant melanoma and 99
      healthy white European controls, and screened a selection of DNA samples for
      polymorphisms in the promoter and 5' untranslated region of the EGF gene by
      analysis. We then screened DNA samples from all participants for the identified
      polymorphism by restriction-fragment-length polymorphism (RFLP) analysis. In
      vitro EGF production was measured in peripheral-blood mononuclear cells from 34
      controls, and the results were compared with the individuals' EGF genotypes.
      FINDINGS: We identified a single nucleotide substitution (G to A) at position 61
      of the EGF gene. Allele frequencies in the controls were 56% EGF 61*A and 44% EGF
      61*G. Cells from individuals homozygous for the 61*A allele produced
      significantly less EGF than cells from 61*G homozygotes (p=0.0004) or
      heterozygous A/G individuals (p=0.001). Compared with the A/A genotype, G/G was
      significantly associated with Breslow thickness (p=0.045) and with risk of
      malignant melanoma (odds ratio 4.9 [95% CI 2.3-10.2], p<0.0001). INTERPRETATION:
      This study suggests that high EGF production might be important in the
      development of malignant melanoma.

PMID- 11844512
TI  - Rural Africa.

PMID- 11844513
TI  - A woman with swollen legs.

PMID- 11844514
TI  - Detection of proximal colorectal cancers through analysis of faecal DNA.
AB  - Detection of mutations in faecal DNA represents a promising, non-invasive
      approach for detecting colorectal cancers in average-risk populations. One of the
      first practical applications of this technology involves the examination of
      microsatellite markers in sporadic cancers with mismatch-repair deficiencies.
      Since such cancers nearly always occur in the proximal colon, this test might be
      useful as an adjunct to sigmoidoscopy, which detects only distal colorectal
      lesions. We report here the first in-depth analysis of faecal DNA from patients
      with proximal cancers to determine the feasibility, sensitivity, and specificity
      of this approach. Using a sensitive method for microsatellite mutation detection,
      we found that 18 of 46 cancers had microsatellite alterations and that identical
      mutations could be identified in the faecal DNA of 17 of these 18 cases.

PMID- 11844515
TI  - Mammographic screening: no reliable supporting evidence?
AB  - Much confusion is being generated by the conclusion of a recent review that
      "there is no reliable evidence that screening for breast cancer reduces
      mortality." In that review, however, there was no appreciation of the appropriate
      mortality-related measure of screening's usefulness; and correspondingly, there
      was no estimation of the magnitude of this measure. We take this measure to be
      the proportional reduction in case-fatality rate, and studied its magnitude on
      the basis of the only valid and otherwise suitable trial. We found reliable
      evidence of fatality reduction, apparently substantial in magnitude.

PMID- 11844516
TI  - Small-for-size partial liver graft in an adult recipient; a new transplant
      technique.
AB  - We report a new technique of adult liver transplantation using a small-for-size
      graft. In order to avoid graft congestion and failure by overperfusion, we
      completely diverted the superior mesenteric venous flow by a mesocaval shunt with
      downstream ligation of the superior mesenteric vein. The recipient recovered
      well, and the graft had normal histology and function at 5 months follow-up.
      Given the current scarcity of cadaveric donors, this technique may increase the
      numbers of adult recipients by using left lobes from cadaveric split liver
      grafts.

PMID- 11844518
TI  - Independent US panel fans debate on mammography.

PMID- 11844517
TI  - Excessive erythrocytosis, chronic mountain sickness, and serum cobalt levels.
AB  - In a subset of high-altitude dwellers, the appropriate erythrocytotic response
      becomes excessive and can result in chronic mountain sickness. We studied men
      with (study group) and without excessive erythrocytosis (packed-cell volume >65%)
      living in Cerro de Pasco, Peru (altitude 4300 m), and compared them with controls
      living in Lima, Peru (at sea-level). Toxic serum cobalt concentrations were
      detected in 11 of 21 (52%) study participants with excessive erythrocytosis, but
      were undetectable in high altitude or sea-level controls. In the mining community
      of Cerro de Pasco, cobalt toxicity might be an important contributor to excessive
      erythrocytosis.

PMID- 11844520
TI  - New directions in the management of atrial fibrillation.

PMID- 11844524
TI  - Medical teams geared up for winter olympics.

PMID- 11844525
TI  - Domestic dispute mars Japan's Afghanistan summit.

PMID- 11844526
TI  - Global fund on AIDS, tuberculosis, and malaria holds first board meeting.

PMID- 11844527
TI  - Nigeria funds launch of nationwide blood-transfusion centres.

PMID- 11844528
TI  - French doctors want french beans instead of french fries.

PMID- 11844530
TI  - S Africa state offers HIV drug to pregnant women.

PMID- 11844531
TI  - US debate on human cloning side tracked by stem cell patent disclosure.

PMID- 11844532
TI  - Spinal-cord injury.
AB  - More than a decade ago, spinal-cord injury meant confinement to a wheelchair and
      a lifetime of medical comorbidity. The physician's armamentarium of treatments
      was very limited, and provision of care for individuals with spinal-cord injury
      was usually met with frustration. Advances in the neurosciences have drawn
      attention to research into spinal-cord injury. Nowadays, advanced interventions
      provide high hope for regeneration and functional restoration. As scientific
      advances become more frequent, scepticism is giving way to the ideas that spinal
      cord injury will eventually be repairable and that strategies to restore function
      are within our grasp. We address the present understanding of spinal-cord injury,
      its cause, pathophysiology, diagnosis, and treatment, and look at promising
      research avenues. We also discuss new treatment options, including functional
      electric stimulation and part-weight-supported walking.

PMID- 11844533
TI  - Schizophrenia and velo-cardio-facial syndrome.
AB  - Velo-cardio-facial syndrome (VCFS), the most frequent known interstitial deletion
      identified in man, is associated with chromosomal microdeletions in the q11 band
      of chromosome 22. The VCFS phenotype is complex, with multiple congenital
      abnormalities affecting several tissues and organs, many of which are derived
      from neural crest cells. Although phenotypic variability occurs, individuals with
      VCFS have high rates of psychiatric disorder, especially schizophrenia.
      Additionally, an increased prevalence of chromosome 22q11 deletions has been
      reported in populations of people with schizophrenia. Furthermore, results of
      molecular genetic studies suggest that a schizophrenia susceptibility locus maps
      to chromosome 22q. These data indicate that aside from being the child of two
      parents with schizophrenia or the monozygotic co-twin of an affected individual,
      VCFS and deletion 22q11 represents the highest known risk factor for the
      development of schizophrenia. Since the entire sequence of chromosome 22 has now
      been identified, the study of VCFS offers a timely and uniquely powerful
      opportunity to identify susceptibility genes for schizophrenia in the general
      population. Furthermore, the strength of the association between schizophrenia
      and VCFS has important implications for the clinical management of these
      disorders.

PMID- 11844534
TI  - Case-control studies: research in reverse.
AB  - Epidemiologists benefit greatly from having case-control study designs in their
      research armamentarium. Case-control studies can yield important scientific
      findings with relatively little time, money, and effort compared with other study
      designs. This seemingly quick road to research results entices many newly trained
      epidemiologists. Indeed, investigators implement case-control studies more
      frequently than any other analytical epidemiological study. Unfortunately, case
      control designs also tend to be more susceptible to biases than other comparative
      studies. Although easier to do, they are also easier to do wrong. Five main
      notions guide investigators who do, or readers who assess, case-control studies.
      First, investigators must explicitly define the criteria for diagnosis of a case
      and any eligibility criteria used for selection. Second, controls should come
      from the same population as the cases, and their selection should be independent
      of the exposures of interest. Third, investigators should blind the data
      gatherers to the case or control status of participants or, if impossible, at
      least blind them to the main hypothesis of the study. Fourth, data gatherers need
      to be thoroughly trained to elicit exposure in a similar manner from cases and
      controls; they should use memory aids to facilitate and balance recall between
      cases and controls. Finally, investigators should address confounding in case
      control studies, either in the design stage or with analytical techniques.
      Devotion of meticulous attention to these points enhances the validity of the
      results and bolsters the reader's confidence in the findings.

PMID- 11844535
TI  - GAVI, the first steps: lessons for the Global Fund.
AB  - The Global Alliance for Vaccines and Immunization (GAVI) is seen as a model for
      the new Global Fund to Fight AIDS, Tuberculosis and Malaria, to be launched early
      in 2002. We did an assessment in four African countries to report the experiences
      of ministries of health and their partners in applying to GAVI for funds to
      strengthen health systems and for new vaccines. Countries welcomed the
      introduction of hepatitis B vaccine, safe injection equipment, and the financial
      support to strengthen immunisation programmes. All reported that the pace of the
      application process was too rapid. District visits revealed low staffing levels,
      insufficient transport and fuel, poorly functioning cold chains, and infrequent
      supervision. Information systems were unreliable, which will be an obstacle to
      GAVI when monitoring and rewarding improvements in immunisation coverage. Also,
      the high cost of expensive new vaccines will be difficult to sustain if GAVI
      funding stops at the end of its 5 year commitment. Our study suggests that
      applications for support and planning for AIDS, tuberculosis, and malaria control
      under the new Global Fund, will be more complex and demanding on already over
      stretched ministries of health. Further, the rapid onset of activities, coupled
      with uncertainty about the time-scale of donor commitment, could be problematic.
      A limited and carefully assessed set of initial activities, focusing on where and
      how to strengthen existing country systems, is more likely to be successful and
      could provide useful models for scaling-up to larger programmes in different
      contexts.

PMID- 11844536
TI  - Screening mammography: setting the record straight.

PMID- 11844537
TI  - Screening mammography: setting the record straight.

PMID- 11844540
TI  - Screening mammography: setting the record straight.

PMID- 11844541
TI  - Rapid prenatal diagnosis of aneuploidies.

PMID- 11844542
TI  - Rapid prenatal diagnosis of aneuploidies.

PMID- 11844543
TI  - Fatigue due to hypocalcaemia.

PMID- 11844544
TI  - Levodopa and recovery after stroke.

PMID- 11844546
TI  - Ethylene glycol poisoning mimicking Snow White.

PMID- 11844547
TI  - Effect of preoperative warming on wound infection.

PMID- 11844549
TI  - Multidrug-resistant Streptococcus pneumoniae from India.

PMID- 11844550
TI  - Japanese HIV-blood trial.

PMID- 11844551
TI  - Bad decision NICE.

PMID- 11844552
TI  - Infectious syphilis and importance of travel history.

PMID- 11844553
TI  - Two decisions of Japanese court on detained Afghan asylum seekers.

PMID- 11844554
TI  - WHO addresses poverty and bioterrorism.

PMID- 11844555
TI  - A cure for anthrax?

PMID- 11844567
TI  - Early life environment modulates 'handedness' in rats.
AB  - Right handedness is one of the most prominent markers of human functional brain
      asymmetry. Deviation from this norm appears to be associated with certain
      developmental disorders. While many studies have dealt with the genetic
      contribution to the determination of handedness, few have examined whether
      environmental factors that are subtler than forced hand switching can modulate
      the development of handedness. In this study, we exposed rats to a novel
      environment for 3 min daily during their first 3 weeks of life and found that
      their paw preferences during both infancy and adulthood showed a leftward shift
      compared with the controls. This result suggests that 'handedness' can be
      modified by rather subtle early environmental manipulation. Since exposure to a
      novel environment does not involve a direct asymmetric activation of the sensory-
      motor system underlying paw-use, mechanisms beyond this paw-specific system must
      exist to mediate the observed modulation of 'handedness'.

PMID- 11844568
TI  - The dorsomedial shell of the nucleus accumbens facilitates cocaine-induced
      locomotor activity during the induction of behavioral sensitization.
AB  - The mesolimbic dopamine system has been intensely studied as the neural circuit
      mediating the locomotor response to psychostimulants and behavioral
      sensitization. In particular, the dopaminergic innervation of the nucleus
      accumbens has been implicated as a site responsible for the manifestations of
      behavioral sensitization. Previous studies have demonstrated an augmented release
      of dopamine in the nucleus accumbens upon a systemic injection of a
      psychostimulant. In addition, alterations in the dopaminergic innervation
      patterns in this brain region have been demonstrated in animals that received
      repeated injections of cocaine. Furthermore, lesions of projection sites that
      have terminations in the nucleus accumbens have demonstrated alterations in
      psychostimulant induced locomotion, both acutely, as well as in sensitization
      paradigms. Since dopamine in the nucleus accumbens is believed to regulate
      several excitatory amino acid inputs, the present study examined the effects of a
      localized electrolytic lesion in the dorsomedial shell of the nucleus accumbens
      in order to better understand the functional role this brain region has in
      behavioral sensitization. All animals received bi-daily injections of 15 mg/kg
      i.p. cocaine. Only those demonstrating behavioral sensitization after a
      subsequent challenge dose were included in the analysis. Following acute exposure
      to cocaine, lesioned animals did not show any difference in their locomotor
      response when compared with sham controls. However, after repeated exposure to
      cocaine, sensitized animals demonstrated a significant attenuation in locomotor
      behavior when compared with sensitized sham controls. This decrease in horizontal
      locomotion persisted 2 days into withdrawal, yet dissipated in the sensitized
      animals that were challenged 2 weeks following their last injection. The data
      presented here demonstrate that the dorsomedial shell of the nucleus accumbens
      plays an important role in the initial stages of behavioral sensitization to
      cocaine.

PMID- 11844569
TI  - A functional neuroanatomical investigation of the role of the medial preoptic
      area in neural circuits regulating maternal behavior.
AB  - The medial preoptic area (MPOA) is essential for normal maternal behavior in the
      rat. Hormone stimulation of the MPOA facilitates the behavior and lesions of the
      MPOA and the adjoining ventral part of the bed nucleus of the stria terminalis
      (vBST) disrupt the behavior. The MPOA/vBST also show increases in Fos protein
      expression during maternal behavior. The present study examines the larger neural
      circuitry within which the MPOA/vBST might operate to influence maternal
      behavior. Combining Fos immunocytochemistry with unilateral excitotoxic amino
      acid lesions or lateral knife cuts of the MPOA/vBST, we sought to identify brain
      regions which might be under the influence of Fos expressing neurons in the
      MPOA/vBST. Two brain regions, the shell of the nucleus accumbens (NAs), and the
      intermediate part of the lateral septum (LSi) were identified. Both the NAs and
      LSi exhibited elevated Fos expression during maternal behavior, while unilateral
      MPOA/vBST damage resulted in an ipsilateral reduction of maternal behavior
      induced Fos expression in each area, suggesting that MPOA/vBST neurons modulate
      Fos expression and associated neural activity in both of these structures during
      maternal behavior. Importantly, these unilateral preoptic lesions also depressed
      maternal behavior-induced Fos expression in the ipsilateral MPOA and vBST. The
      effects of these lesions on Fos expression in the periaqueductal gray (PAG) and
      other brain regions are also presented.

PMID- 11844570
TI  - Effects of antihypertensive drugs on ultrasound production and cardiovascular
      responses in 15-day-old rats.
AB  - When exposed to extreme cold or injected with the alpha(2)-adrenoceptor agonist,
      clonidine, infant rats emit ultrasonic vocalizations (USVs). Based upon the
      cardiovascular changes that accompany these two manipulations, especially
      decreased venous return, it was hypothesized that USVs are the acoustic by
      product of the abdominal compression reaction (ACR), a maneuver that increases
      venous return. If this hypothesis is correct, then other anithypertensive drugs
      that decrease venous return should evoke USVs. In Experiment 1, sodium
      nitroprusside (SNP, 400 microg/kg), a direct-acting dilator of arteries and
      veins, was administered to 15-day-old rats under thermoneutral conditions while
      cardiac rate and ultrasound production were monitored. In Experiment 2, femoral
      artery pressure was monitored after SNP administration. Infants responded to SNP
      administration with decreased arterial pressure and tachycardia and, in addition,
      significantly increased ultrasound production. In Experiment 3, chlorisondamine
      (5 mg/kg), a ganglionic blocker that causes vasodilation and bradycardia, and
      hydralazine (20 mg/kg), a selective dilator of arteries, was administered to 15
      day-olds. As predicted, chlorisondamine evoked ultrasound production and
      hydralazine did not. These results introduce SNP and chlorisondamine as only the
      second and third known agents capable of independently evoking USVs in
      thermoneutral conditions, and provide further support for the notion that
      ultrasound production is triggered by decreased venous return.

PMID- 11844571
TI  - Evidence for changes in brain enkephalin contents associated to male rat sexual
      activity.
AB  - Indirect evidence suggests that ejaculation might activate endogenous opioid
      systems, which exert an inhibitory influence on male rat sexual behaviour. The
      objective of the present study was to search for putative long-term changes in
      the contents of immunoreactive (IR) Met-enkephalin (IR-Met), Leu-enkephalin (IR
      Leu) and opioid octapeptide Met--Arg(6)--Gly(7)--Leu(8) (IR-Oct) in specific
      brain areas, after the execution of different amounts of sexual activity.
      Additionally, basal contents of these enkephalins were compared between sexually
      active (SA) and persistent sexually inactive (SI) rats. Immunoreactivity to
      enkephalins was determined by radioimmunoanalysis, in the frontal cortex, the
      hypothalamus and midbrain of SA and SI rats, as well as 24 or 48 h after males
      had one ejaculation or copulated to exhaustion. Twenty-four hours after sexual
      activity, there was a generalised increase in enkephalin contents that returned
      to control values at the 48 h measurement in all brain areas, but the
      hypothalamus, where IR-Met and IR-Oct remained elevated. No differences in the
      magnitude of the changes were found between rats that ejaculated once and
      sexually satiated males. IR-Oct concentration in the hypothalamus of SI rats
      appeared significantly higher than in SA animals, with no differences in IR-Met
      and IR-Leu. Results give direct evidence of the activation of endogenous opioid
      systems by male rat sexual activity. The occurrence of long lasting increases in
      the contents of IR-Met and IR-Oct in the hypothalamus of rats that copulated was
      detected. Finally, an intrinsically elevated octapeptide concentration in the
      hypothalamus of SI rats was found.

PMID- 11844572
TI  - Quantifying song bout production during zebra finch sensory-motor learning
      suggests a sensitive period for vocal practice.
AB  - Using an event-triggered recording system, the quantity of daily song bout
      production was measured weekly in male zebra finches (Taeniopygia guttata) during
      sensory-motor learning and at one year of age. Our aim was to ask whether the
      development of a stereotyped vocal pattern involves a practice-driven component.
      If so, we hypothesized that juvenile males learning song should sing more often
      than adults reciting a vocal pattern they had already learned, and that greater
      levels of juvenile singing should be associated with improvement in the quality
      of the adult song. Across the period measured (36-365 days of age), subjects
      showed an inverted U-shaped pattern of daily song bout production. Song bout
      production was lowest during subsong, with increased production associated with
      plastic song and song crystallization, although individual differences were
      large. Daily song bout production decreased in adulthood. Higher levels of song
      bout production during plastic song correlated with fewer sequencing errors in
      adult song patterns (r(2)=0.77). In contrast, quantity of singing during song
      crystallization showed no relationship to vocal stereotypy (r(2)=0.002). Our data
      suggest a sensitive period for vocal practice during zebra finch sensory-motor
      learning with consequences for the note-sequence fidelity of the adult vocal
      pattern.

PMID- 11844573
TI  - Amygdala or ventral hippocampal lesions at two early stages of life
      differentially affect open field behaviour later in life; an animal model of
      neurodevelopmental psychopathological disorders.
AB  - Psychiatric disorders like schizophrenia or autism are thought to result from
      disruption of the normal pattern of brain development. Abnormalities in the
      amygdaloid complex and hippocampus have been reported in these disorders. In the
      present study rats were lesioned in the amygdala or ventral hippocampus on day 7
      of life (immature brain) or day 21 of life (almost mature brain) and open field
      behaviour was determined later in life before and after puberty. Lesioning on day
      7 resulted in behavioural changes, interpreted as locomotor stereotypy and
      decreased anxiety in case of amygdala or hippocampus, respectively. These effects
      were more profoundly present after puberty. Lesioning on day 21 did not result in
      these behavioural changes, which subscribes to the importance of the stage of
      brain maturation on functional development. The results suggest that the
      behavioural changes in rats lesioned on day 7 may due to a malfunctioning of
      structures connected to the amygdala or ventral hippocampus. Brain lesions made
      on day 7 of life may serve as a potential model of psychopathological
      neurodevelopmental disorders.

PMID- 11844574
TI  - AT(2) but not AT(1) receptor antagonism abolishes angiotensin II increase of the
      acquisition of conditioned avoidance responses in rats.
AB  - In this study we attempted to determine behavioural, including cognitive,
      consequences of the brain AT(1) (losartan, 2 nmol), AT(2) (PD 123319, 1.5 nmol),
      and joint AT(1)/AT(2) angiotensin receptors blockade. Male Wistar rats (160-180
      g) were injected into the left cerebral ventricle with the above doses of the
      blockers dissolved in 0.9% NaCl solution (vehicle) or with the vehicle alone.
      Five minutes later they received, to the right cerebral ventricle, 1 nmol of
      angiotensin II (Ang II) dissolved in vehicle or the vehicle alone. Ang II
      consistently increased rate of acquisition of conditioned avoidance response
      (CARs) and facilitated recall of the passive avoidance behaviour. In one out of
      the three series of experiments in open field Ang II stimulated rats locomotor
      activity. Losartan and PD 123319, both ineffective alone, given prior to Ang II
      abolished all the behavioural changes produced by the peptide except for the Ang
      II facilitation of CARs acquisition, which was unchanged by losartan.
      Interestingly, joint injection of losartan and PD 123319 significantly decreased
      the rate of CARs acquisition both in control and Ang II treated animals. In
      conclusion, the present data suggest significant though different involvement of
      both AT(1) and AT(2) angiotensin receptors in cognitive processes.

PMID- 11844575
TI  - Residual effects of daytime administration of melatonin on performance relevant
      to flight.
AB  - There is a general consensus that melatonin possesses time-dependent hypnotic
      effects, but there is no information yet whether it has residual effects on
      neurobehavioral performance, especially after daytime administration. In the
      present study we investigated the possible residual effects of 3 mg melatonin on
      performance relevant to flight and on subjective feelings of sleepiness, arousal,
      activation and affect after a daytime nap, as a function of nap length. Fifteen
      reserve pilots of the Israeli Air Force participated in the study. The experiment
      consisted of four sessions during which either melatonin or placebo was
      administered at 16:00 h. In two conditions, subjects were allowed to sleep for 2
      h (17:00-19:00 h) whereas in the other two only a 0.5-h nap was allowed. After
      the naps they started performing a flight simulator task every 2 h. Sleep
      efficiency significantly increased and sleep latency significantly decreased in
      both melatonin conditions compared to placebo. Flight performance was only mildly
      affected in the 0.5-h nap condition. Subjective assessment of sleepiness
      significantly differed between the two treatment conditions, only in the 0.5-h
      nap condition. Subjects felt sleepier 2-4 h after melatonin administration. To
      conclude, our data suggest that administration of melatonin before a brief
      daytime nap (about 0.5 h) may be associated with mild residual effects on
      psychomotor performance and may significantly affect subjective feeling of
      sleepiness for 2-4 h.

PMID- 11844576
TI  - Sensitization to cocaine after a single intra-cerebral injection of orphanin
      FQ/nociceptin.
AB  - Orphanin FQ/nociceptin (OFQ/N) has been shown to modulate mesolimbic dopaminergic
      neurotransmission. Repeated administration of OFQ/N into the ventral tegmental
      area results in a sensitized locomotor response to subsequent peripheral cocaine
      administration. The aim of the present study was to examine the potential for
      OFQ/N to produce a sensitized locomotor response to cocaine after a single intra
      VTA administration and to determine if this effect of OFQ/N extrapolates to other
      points along the mesolimbic or nigrostriatal dopaminergic axes. Bilateral
      administration of OFQ/N (30 microg/side) into the VTA on day 1 to male Sprague-
      Dawley rats resulted in an enhanced locomotor response to cocaine (10 mg/kg i.p)
      administered on day 2. However, OFQ/N (3, 10 and 30 microg per side) administered
      on day 2, 5 mins prior to the administration of cocaine (10 mg/kg i.p), in
      animals treated with aCSF or OFQ/N on day 1, similarly blocked the action of
      cocaine, suggesting that the sensitized response was not due to tolerance to the
      effect of endogenously released OFQ/N. The administration of OFQ/N into the
      substantia nigra or nucleus accumbens failed to produce a significant sensitized
      response to a cocaine challenge 24 h later. A significant increase in cocaine
      stimulated locomotor response on day 2 was observed after injection of OFQ/N into
      the striatum on day 1. These results demonstrate the ability of a single intra
      VTA or intra-striatal administration of OFQ/N to produce increases in the
      sensitivity to cocaine and may indicate a role for endogenous OFQ/N systems in
      regulating responses to psychostimulant drugs.

PMID- 11844577
TI  - Modulation of flash stimulation intensity and frequency: effects on visual evoked
      potentials and oscillatory potentials recorded in awake, freely moving mice.
AB  - Visual evoked potentials (VEP) responses to flash stimulation at nine
      intensities, from 0.611 to 945.6 cd/m(2)*s, and two frequencies (0.2 and 1 Hz)
      were recorded and oscillatory potentials (OPs) extracted after digital 50-Hz high
      pass filtering in unanaesthetized unrestrained mice. Both VEP and OPs morphology
      were replicable for all conditions and were similar to values reported in the
      literature. In particular OPs spectral analysis showed that the main frequency
      component remained stable at 66-77 Hz, for both stimulation frequencies, although
      it displayed an increase in amplitude, as a function of stimulus intensity. OPs
      amplitude at 1 Hz versus 0.2 Hz stimulus frequency was higher after taking into
      account the different noise contributions in the two conditions. Root mean square
      values calculated at selected time windows, revealed that, at 1 Hz, the main
      contribution to OPs occurs at the onset of the response (14-27 ms) while, at 0.2
      Hz, the higher RMS was recorded later (42-56 ms). This difference accounts for
      the longer duration of the oscillatory event in the 0.2-Hz condition and suggests
      that oscillatory activity, modulated and carried along the visual pathway, is
      recorded at the cortical electrode after further elaboration at the
      cortical/subcortical level, depending on stimulus properties.

PMID- 11844578
TI  - The effects of ventral tegmental administration of GABA(A), GABA(B), NMDA and
      AMPA receptor agonists on ventral pallidum self-stimulation.
AB  - The ventral pallidum (VP) is a basal forebrain structure that is interconnected
      with motor and limbic structures and may be considered as an interface between
      motivational and effector neural signals. Results from a considerable number of
      studies suggest that this structure is critically involved in reward-related
      behavior. The VP shares reciprocal connections with other reward-implicated
      regions, such as the ventral tegmental area (VTA). This anatomy predicts that
      drug-induced neuronal alterations in the VTA could profoundly alter the function
      of the VP. Here, using the curve-shift intracranial self-stimulation method, we
      studied the effects of muscimol (GABA(A) agonist), baclofen (GABA(B) agonist),
      NMDA and AMPA, microinjected bilaterally into the VTA on the rewarding efficacy
      of VP self-stimulation. Central injections of the highest dose of muscimol (0.128
      microg) resulted in significant elevations in VP self-stimulation thresholds,
      indicating a reduction in the rewarding efficacy of the stimulation. Elevations
      in VP self-stimulation thresholds were also evident after intrategmental
      injections of higher doses of baclofen (0.12, 0.48 microg). By contrast,
      intrategmental activation of NMDA and AMPA receptors did not affect reward
      thresholds. These findings suggest that GABAergic and glutamatergic transmission
      in the VTA activate different circuits that may mediate different functions.
      Thus, the VTA--VP projection activated by GABA modulates VP stimulation reward,
      while the projection activated by glutamate may be involved in reward-unrelated
      effects, rather than in the processing of reward. The decreased rewarding
      efficacy of VP self-stimulation following intrategmental injections of muscimol
      and baclofen may be due to GABAergic modulation of ventral tegmental dopaminergic
      and nondopaminergic neurons projecting to the VP.

PMID- 11844579
TI  - Evidence for involvement of glucocorticoid response in the hippocampal changes in
      aged molarless SAMP8 mice.
AB  - The involvement of glucocorticoid response in the hippocampal changes in aged
      SAMP8 mice after removal of their upper molar teeth (molarless condition) was
      examined using biochemical, morphological and behavioral techniques. Molarless
      mice showed plasma corticosterone levels to be significantly greater than those
      in molar-intact control mice. Pretreatment with metyrapone, which suppresses the
      stress-induced rise in plasma corticosterone levels, prevented the molarless
      condition-induced increase in plasma corticosterone levels, reduction in CA1
      pyramidal neuron numbers, and impairment of spatial learning. The results suggest
      a link between the molarless condition and the glucocorticoid response, which may
      be involved in spatial learning deficits and hippocampal neuronal death in aged
      SAMP8 mice.

PMID- 11844580
TI  - Working memory in capuchin monkeys (Cebus apella).
AB  - It has been suggested that delayed (non-) matching to sample (DNMTS/DMTS) tasks
      using trial-unique stimuli and short, as well as longer delay intervals, can
      provide important insights into animal cognition. Therefore, this research
      examined the capability of the New World capuchin monkey (Cebus apella) in
      perform trial-unique DMTS and DNMTS tasks across delay intervals ranging between
      8 s and 10 min. Subjects were tested using a version of the Wisconsin General
      Test Apparatus mounted in front of the animal's home cage. They were first
      trained on a basic DMTS/DNMTS task with an 8 s interval until they reached a
      learning criterion of nine correct responses in ten consecutive trials. All
      subjects reached the learning criterion in both DMTS/DNMTS tasks, and the number
      of trials to criterion did not differ between tasks. After reaching the
      criterion, subject's memory performance was successively assessed at delay
      intervals of 15 s, 60 s, 120 s and 10 min. For both DMTS/DNMTS tasks, the mean
      percentage of correct responses across delays was above chance and,
      interestingly, performance did not significantly decrease as function of delay
      increments. Comparisons based on each group's scores, averaged across the four
      delays, showed no difference between DMTS and DNMTS memory performance. These
      results indicate that capuchin monkeys are able to learn DMTS/DNMTS tasks in
      which they are required to respond to new pairs of stimuli on every trial. This
      demonstrates the capability of 'concept' learning in this species. Moreover,
      above chance performance on the memory tests indicates a working memory ability
      similar to that reported for the genus Macaca. Taken together, these data
      indicates that capuchin monkeys can be a valuable alternative model for
      investigations of the neuropsychological basis of memory.

PMID- 11844581
TI  - The behavioural effect of middle cerebral artery occlusion on apolipoprotein-E
      deficient mice.
AB  - The behavioural effects of middle cerebral artery occlusion (MCAO) in
      apolipoprotein-E deficient (Apo-E KO) mice were investigated using a modified
      SHIRPA protocol and compared with effects in wild type littermate controls. The
      MCA was permanently occluded by insertion of an intraluminal filament to its
      origin on the Circle of Willis and behavioural responses were observed 24 h
      later. MCAO treatment caused a range of changes in the wild type mice whereas,
      few differences were observed in the Apo-E KO mice in the behavioural
      observation. In the rotarod task, MCAO operated wild type mice showed a
      significant reduction in performance compared with sham-operated and non-operated
      animals. In contrast, both sham and MCAO operated Apo-E KO mice showed
      significant impairment compared with non-operated controls. A significant
      reduction in performance was also observed in sham-operated Apo-E KO compared
      with sham-operated wild type mice. In locomotor activity tests, no significant
      reduction in activity was observed between non-operated and sham-operated wild
      type controls, whereas a significant reduction was found between sham operated
      and MCAO operated mice. In the Apo-E KO mice, both sham and MCAO-operated animals
      showed a reduction in locomotor activity compared with non-operated mice.
      Furthermore, Apo-E KO MCAO mice showed a worsened deficit in locomotor activity,
      which was significantly correlated with exacerbated cortical lesion volume,
      unlike wild-type MCAO mice. This study shows that Apo-E KO animals demonstrate an
      impaired functional recovery post surgery which may be further compounded by post
      experimental stroke and also demonstrates the utility of the SHIRPA test system
      for investigating behavioural changes in functional outcome post stroke.

PMID- 11844582
TI  - Effects of histamine H(3) receptor ligands GT-2331 and ciproxifan in a repeated
      acquisition avoidance response in the spontaneously hypertensive rat pup.
AB  - Histamine H(3) receptor antagonists have been proposed as potentially useful
      therapeutic agents for the treatment of several disorders including attention
      deficit, schizophrenia, depression, and Alzheimer's disease. We have developed a
      repeated acquisition version of an inhibitory avoidance task using spontaneously
      hypertensive rat (SHR) pups that we believe provides a reproducible measure of
      the cognitive and attention deficits often characteristic of these disease
      states, and evaluated two H(3) receptor antagonists. Male SHR, Wistar (WI) and
      Wistar Kyoto (WKY) rat pups (20--24 days old) were trained to avoid a mild
      footshock (0.1 mA, 1 s duration), delivered when the pup had transferred from a
      brightly lit to a darkened compartment. After the first trial, the pup was
      removed and returned to its home cage. One minute later, the same pup was
      replaced in the brightly-lit compartment and the training process repeated. A
      total of five trials were recorded. SHR pups performed significantly more poorly
      than WI or WKY pups using this training schedule, and SHR pups were used for all
      subsequent studies. Methylphenidate and ABT-418, both clinically active in
      attention deficit hyperactivity disorder (ADHD), were tested to validate the
      model. Methylphenidate (1 and 3 mg/kg s.c.) and ABT-418 (0.03 mg/kg s.c.)
      significantly improved SHR pup performance. The H(3) receptor antagonists GT-2331
      (1 mg/kg s.c.) and ciproxifan (3 mg/kg s.c.), also significantly, and in a dose
      related manner, enhanced performance of the SHR pups. (R)-alpha-methylhistamine
      (3 mg/kg s.c.) blocked the pro-cognitive effects of ciproxifan, suggesting an
      H(3) receptor site of action for this compound. This model is useful for
      evaluating the cognition/attention-enhancing potential of H(3) receptor
      antagonists.

PMID- 11844583
TI  - Neural correlates of visuospatial imagery.
AB  - We studied changes in regional cerebral blood flow (rCBF) in 10 healthy right
      handed subjects during a visuospatial imagery task. The subject's task consisted
      of drawing imagined lines connecting encircled numbers in ascending order and
      estimating the number of lines crossing. Compared with a control task in which
      there were no crossed lines, there were significant rCBF increases in the
      cingulate gyrus, the adjacent superior frontal gyrus and in the left inferior
      parietal cortex. The rCBF changes of the latter area correlated with task
      performance time. Since these activation areas are close to those in imagery of
      movement trajectories, we concluded that they appear to be a subsystem for
      processing mental visuospatial images.

PMID- 11844584
TI  - Comparison between macaques' and humans' kinematics of prehension: the role of
      morphological differences and control mechanisms.
AB  - Reaching and grasping has been widely studied in both macaques and humans, mainly
      with the aim of finding similar patterns of behavior in the two species. Little
      attention has yet been given to how morphological and behavioral differences
      between the two species might affect the kinematics of the movement. In this
      study, we present a careful analysis of the similarities and differences between
      humans' and macaques' prehension movements and discuss these with respect to both
      the control system and the biomechanics of the arm. Five humans and five macaques
      performed the same task, namely grasping small feeding objects using a precision
      grip. Macaques were observed in unconstrained conditions, free to adjust their
      body posture. The behavioral protocol for macaques revealed a postural preference
      for sitting and keeping the elbow slightly flexed when applying a precision grip.
      In agreement with the literature, kinematics revealed general features of
      movement common to both humans and macaques. However, within a similar timeframe,
      macaques produced steeper and wider excursion of the elbow and of the wrist,
      smaller abduction of the shoulder joint and larger displacement of the torso than
      humans did. The three-joint limb revealed stronger irregularities for the
      macaques. We hypothesize that the larger kinematic irregularities and the
      specific elbow--shoulder posture in macaques result in part from an effort of the
      control system to compensate for different biomechanical constraints, namely for
      limited shoulder-joint excursion, in order to achieve a similar range of comfort
      of motion. Finally, we briefly consider the influence of primitive neural
      circuits responsible for arm motion during locomotion and speculated on their
      influence on the control of reaching in macaques.

PMID- 11844585
TI  - Rats can track odors, other rats, and themselves: implications for the study of
      spatial behavior.
AB  - In order to demonstrate that rats solve dead reckoning (path integration) tasks
      in which they return to a starting location using self-movement (idiothetic)
      cues, it is necessary to remove external (allothetic) cues. Odor cues, especially
      those generated by a rat on a single passage, are difficult to control and they
      can potentially serve as a cue to guide a homeward trip. Because it is presently
      unknown whether rats can track the cues that they themselves leave, as opposed to
      the odor trails left by other rats, we investigated this question in the present
      study. A tracking task was used in which rats: (1) followed a scented string from
      a refuge to obtain a food pellet located on a large circular table; (2) followed
      odors left on the table; (3) followed odors left by the passage of another rat;
      or (4) followed odors left by themselves. Groups of rats were presented with
      strings scented with either the rat's own odor (Group Own), a conspecific's odor
      (Group Other), or another scent, vanilla (Group Vanilla). After training, a
      series of discrimination tests were given to determine the nature of the stimulus
      that controls scent tracking. The results indicated that Own, Other, and Vanilla
      groups were equally proficient in discriminating and following their respective
      odors. The rats were also able to follow odor trails on the table surface as well
      as a trail left by the single passage of another rat or their own passage. This
      is the first study to demonstrate that rats can discriminate between conspecific
      odors and their own odor left during a single passage. The results are discussed
      in relation to their implications for experimental methodology and olfactory
      contributions to spatial navigation in general and dead reckoning in particular.

PMID- 11844586
TI  - Influence of a dietary n-3 fatty acid deficiency on the cerebral catecholamine
      contents, EEG and learning ability in rat.
AB  - Female rats were fed on a diet deficient in (n-3) fatty acid or enriched in
      docosahexaenoic acid (DHA) diet from mating and throughout pregnancy and
      lactation. Pups fed on the same diet as their dams were used for experiments. The
      effects of dietary (n-3) fatty acid deficiency on cerebral catecholamine contents
      and electroencephalogram (EEG) in rat pups during the postnatal development were
      investigated. The (n-3) deficient rat pups showed significantly lower levels of
      noradrenaline (NA) in cerebral cortex, hippocampus and striatum, compared with
      those in the DHA adequate rats. Dopamine (DA) contents were significantly lower
      in the (n-3) deficient rats until the 7th day of age. These results were
      consistent with observations in the EEG analysis, relative powers of fast
      activities in the EEG recorded from the (n-3) deficient rats were significantly
      lower than those in the DHA adequate rats. The effect of supplementation with DHA
      in (n-3) deficient rats on learning ability was also studied in a model of
      learning, active avoidance test and three-panel run way test, after weaning.
      Although the percentages of avoidance in the (n-3) deficient rats (saline group)
      were constantly 20% or less until the 3rd session, the percentage of avoidance in
      the DHA supplemented rats rapidly increased to 53% following the first
      administration. While in the three-panel runway test, there were no significant
      differences between two groups. These results suggest that chronic consumption of
      a (n-3) fatty acid deficient diet could modify the biosynthesis of catecholamine
      in the brain, and might induce the behavioral disturbances. Furthermore, the
      decreased learning ability induced by (n-3) deficiency in the active avoidance
      test is a reversible following a supplementing DHA after the weaning.

PMID- 11844587
TI  - Induction of a brainstem correlate of conditioned taste aversion expression: role
      of the pontine parabrachial nucleus.
AB  - Increases in Fos-like immunoreactivity (FLI) in the intermediate division of the
      nucleus of the solitary tract (iNTS) are seen following the expression of a
      conditioned taste aversion (CTA). In studies limited to behavioral assessment,
      the pontine parabrachial nucleus (PBN) has been demonstrated to play a critical
      role in the acquisition, but not the expression, of CTAs. To better define the
      role of the PBN in taste aversion learning, the present study examined the
      effects of PBN lesions on FLI in iNTS in animals with lesions placed either
      before or after CTA training. As is the case with behavioral expression of a CTA,
      timing of PBN lesions was found to be critical. Lesions placed prior to
      conditioning blocked evidence of conditioning, including both taste rejection and
      FLI in iNTS. Lesions placed after conditioning, but before testing, did not
      interfere with either taste rejection or FLI. These results support and extend
      prior claims that PBN is critical for CTA acquisition but not expression. They
      also demonstrate that input from PBN to iNTS is not necessary for the FLI seen
      there during CTA expression.

PMID- 11844589
TI  - MK-801 induced amnesia for the elevated plus-maze in mice.
AB  - MK-801, a non-competitive NMDA receptor antagonist, has been shown to have
      amnesic properties in animal models. The purpose of the present study was to
      examine potential amnesic effects of MK-801 in mice using the modified elevated
      plus-maze paradigm. An animal was placed on the distal end of an open arm, and
      the transfer latency, i.e. the time in which it moves to the enclosed arm, was
      measured. Four different experimental schedules (i.e. the combination of the
      treatment and the testing) were used: MK-801 (0.075, 0.15, 0.25 and 0.4 mg/kg or
      saline) were given (a) 30 min before the acquisition session, (b) immediately
      after the acquisition session, (c) 60 min after the acquisition session, and (d)
      30 min before the retention session. The retention session always followed 24 h
      after the acquisition session. Analysis of data showed a significant shortening
      of the transfer latency in saline-treated animals during the retention session.
      Further, MK-801 (at the dose range of 0.15--0.4 mg/kg) administered before and
      immediately after the acquisition session as well as before the retention session
      prolonged the transfer latency during the retention session. In fact, transfer
      latencies in MK-801 treated mice did not differ from those measured during the
      acquisition session. Thus, prolongation of the transfer latency in MK-801-treated
      mice indicates deficits in 'memorization' processes. On the contrary, MK-801
      given 60 min after the acquisition session failed to increase the transfer
      latency, which suggests that the memory trace was sufficiently consolidated at
      this time. Based on the present results, the glutamatergic NMDA receptor
      mechanisms play an important role in a spatial orientation of mice placed on the
      elevated plus-maze.

PMID- 11844588
TI  - Oxidative damage causes formation of lipofuscin-like substances in the
      hippocampus of the senescence-accelerated mouse after kainate treatment.
AB  - We have demonstrated that seizures induced by kainic acid (KA) are, at least in
      part, mediated via oxidative stress in rats [Life. Sci. 61 (1997) PL373; Brain
      Res. 853 (2000) 215; Brain Res. 874 (2000) 15; Neurosci. Lett. 281 (2000) 65]. In
      order to extend our findings, we employed the rodent aging model in this study.
      After KA treatments (once a day for 5 days; 20,20,20,20 and 40 mg/kg, i.p.),
      several parameters reflecting neurotoxic behaviors, oxidative stress
      [malondialdehyde (MDA) and protein carbonyl] and aging (lipofuscin-like
      substances) were compared between senile-prone (P8) and resistant (R1) strains of
      9-month-old male senescence-accelerated mice (SAM). KA-induced neurotoxic signs
      as shown by mortality and seizure activity were more accentuated in the SAM-P8
      than in the SAM-R1. Levels of MDA and carbonyl are consistently higher in the
      hippocampus of SAM-P8 than that of SAM-R1. Significant increases in the values of
      MDA and carbonyl were observed 4 h or 2 days after the final KA administration.
      This finding was more pronounced in the SAM-P8 than in the SAM-R1. Although a
      significant loss of hippocampal neurons was observed 7 days post-KA, at this time
      the MDA and carbonyl content had returned to near control levels. In contrast,
      fluorescent lipofuscin-like substances and lipofuscin granules were significantly
      increased 7 days after KA treatments. Therefore, our data suggests that mice in
      the senescence model are more susceptible to KA-induced seizures/oxidative
      damage, and that oxidative damage could be one of the casual factors in the
      accumulation of lipofuscin.

PMID- 11844590
TI  - [Knee orthosis. Evaluation of clinical efficiency with a review of the
      literature].
AB  - INTRODUCTION: The aim of this work was to collect literature data to assess the
      knee orthosis use with controlled clinical trials. METHOD: The international
      literature relating to the years 1980-2000 was carried out with the Medline data
      bank. RESULTS: Five hundred and twelve articles were collected and 35 were
      retained, 32 related to clinical studies and three related to toxicity. The
      evaluations were performed with either functional tests or clinical studies. The
      open-non controlled clinical trials are far higher than prospective comparative
      clinical trials that were developed only during last years. Main criteria of
      judgement are articular stability, functional pain and clinical index. Most of
      studies focused the anterior cruciate ligament lesions, patellar pains and
      osteoarthritis. DISCUSSION: This review of the literature may help to determine
      the interest and the limits of orthosis use as well as side effect occurrence.
      Both these clinical and experimental data point out the methodological
      difficulties facing the investigatory clinician in knee orthosis evaluation.
      CONCLUSION: Many studies contributed to the clinical evaluation of the knee
      orthosis. This work highlights various clinical indications for the same orthosis
      and variable results for the same indication. These methodological difficulties
      may not prevent a further evaluation of these devices to improve their use in
      current practice.

PMID- 11844591
TI  - [Influence of testing position on lumbar isokinetic measurements].
AB  - The studies carried out on the lumbar spine, using an isokinetic type machine,
      showed the importance of the extensor muscles and the force they develop,
      compared with the flexor muscles. Both the sitting and standing positions were
      used without determining the better position. MAIN OBJECTIVE OF THE STUDY: To
      determine how the patients position influenced the performance of the muscles. We
      also studied a new parameter : the angle to maximal peak torque (APT). MATERIAL
      AND METHOD: 17 healthy subjects and 19 suffering from low back pain were chosen.
      We perform the test in both positions for each subject. We compare in each group
      the peak torque of the extensor and flexor muscles on both positions and the
      angle of this torque. RESULTS: Low back pain subjects flexor/extensor ratio were
      1.71 sitting and 1.56 standing. Healthy subjects showed normal ratio of 0.69 and
      0.84. CONCLUSION: The position of the subject has no influence on the results in
      the low back pain subjects, and the sitting position is preferred. The angle of
      development of the maximal peak torque in both groups of muscles was very
      interesting, especially in the subjects suffering from low back pain and shines a
      new light on the different functions of the muscles of the low back pain
      suffering subjects and the healthy subjects. This angle (APT) is inversed in low
      back pain subjects who develop more torque for the extensors in extension of the
      spine.

PMID- 11844592
TI  - [Results of rehabilitation on quality of walking and outcome in elderly patients
      following femoral neck fracture. Development after one year].
AB  - OBJECTIVES: To examine effects of coordinated multidisciplinary inpatient
      rehabilitation for older patients with hip fractures. MATERIAL AND METHOD: 187
      (42 men and 147 women: mean age 80.9 +/- 8.4 years) admitted with a diagnosis of
      fracture neck of femur. Before fracture 183 patients were living in their own
      house. We examine medical state before fracture, type of fracture, type of
      surgery, walking performance at hospital discharge and at one year, destination
      at this discharge, living location and quality of life at one year. RESULTS: The
      length stay after intracapsular fracture and prosthesis is significatively lower
      (p<0.01). At discharge 28% were walking alone, 38% with stick, 17% with technical
      aid, 8% with human aid, 2% were bedridden and 7% were dead. After hospitalisation
      7% were dead, 70% were living in their own homes, 18% were in old people's homes
      and 6% in another hospital. One year after fracture, 19% were dead, 65% were
      living in their own homes, 16% were in old people's homes. Older age, medical
      state before fracture and male gender was found to increase mortality risk
      following hip fracture (p<0.01). CONCLUSIONS: Hip fracture is a major cause of
      morbidity in older people and its impact, both on the individual and to society
      is substantial. Many people do not return to their pre-fracture life style.
      Coordinated multidisciplinary care of patients with fractured neck of femur seems
      essential.

PMID- 11844593
TI  - [Are age and urodynamic data correlated in women with stress urinary incontinence
      (SUI)?].
AB  - PURPOSE: Our aim was to evaluate the impact of age on lower urinary tract
      function in women by means of urodynamics and modelized analysis of the recorded
      free uroflow curves. MATERIAL AND METHODS: One hundred and fifty three women (age
      range: [30-93 years]; 6 decades A to F) with only SUI complaint underwent a
      urodynamic evaluation which included initial free uroflow, urethral pressure
      profile, cystometry and final free uroflow at bladder functional capacity.
      Modelized analysis was performed using the VBN mathematical micturition model;
      from comparison between recorded and computerized theoretical flow curves this
      model allows to determine two characteristic parameters: one of urethral
      obstruction and one of detrusor efficiency. RESULTS: No age-related changes were
      found in bladder capacity, peak flow rate in the first void and post residual
      volume. A significant increase of peak flow rate was noted in the second void for
      D and older. Bladder compliance decreased only from E. As usually described a
      decrease with age of the maximum urethral closure pressure occurred while the
      functional urethral length decreased only from E. A flat distribution of the VBN
      parameters was observed. DISCUSSION-CONCLUSION: This study shows the absence of
      age-associated changes in both urodynamic data and VBN parameters in a population
      of women with SUI and without any other disease. These findings reinforce the
      idea that chronological age does not strongly correlate with the physiological
      status.

PMID- 11844594
TI  - Genetic determinants of lung cancer short-term survival: the role of glutathione
      related genes.
AB  - PURPOSE: Survival of lung cancer patients has been dismal. Glutathione enzymes
      are directly involved in the metabolism of platinum compounds, a group of
      important chemotherapeutic drugs in cancer treatment. We tested the hypothesis
      that genes encoding glutathione enzymes may predict lung cancer short-term
      survival. METHODS: We studied DNA polymorphisms of 250 primary lung cancer
      patients at four glutathione-related loci: GSTP1, GSTM1, GSTT1 and gamma-GCS that
      encode glutathione-S-transferase-pi, glutathione-S-transferase-mu, glutathione-S
      transferase-theta, and gamma-glutamylcysteine synthetase, respectively. Pearson's
      chi(2)-square tests, Kaplan-Meier survival curves, log rank tests, and Cox
      regression models were applied in the analysis. RESULTS: There were 150 (60%) men
      and 100 (40%) women in this study. Seventeen percent of the patients had never
      smoked cigarettes, and 61% had stopped smoking at least 6 months prior to their
      lung cancer diagnosis. Among never smokers, those with null (N) or low (L)
      genotype experienced a better 1-year-survival rate than those with a positive (P)
      or high (H) genotype. Patients with P or H at two loci (PP or PH) were compared
      with patients with N or L at one or both loci (other). Among never smokers, 1
      year-survival rates were 60-78% for patients with PP or PH genotypes compared
      with 89-100% for other types. The survival advantage was greater among advanced
      stage patients who were NL or NN than low-stage patients. Similar results were
      not observed among smokers. CONCLUSIONS: Glutathione-related genes may determine
      lung cancer survival. Our results, if confirmed, would suggest new directions to
      enhance cancer treatment, and provide easily measurable markers for clinicians to
      plan patient-specific therapy.

PMID- 11844595
TI  - A link between the p53 germ line polymorphisms and white blood cells apoptosis in
      lung cancer patients.
AB  - The p53 protein acts as a checkpoint in the cell cycle, either preventing or
      initiating apoptosis. Since cancer is the unchecked proliferation of cells, p53s
      role is critical. Thus, we have sought a link between the p53 polymorphisms and
      apoptosis. Wild-type p53 tumor suppressor gene exhibits several common single
      nucleotide polymorphisms (SNP) both in coding and non-coding regions. We focused
      on two of them, the p53 BstUI SNP on the fourth exon, and the p53 MspI SNP on the
      sixth intron. We investigated a presence of these two polymorphisms in relation
      to apoptosis of white blood cells in lung cancer patients and healthy controls.
      We found that both the p53 BstUI and the p53 MspI homozygous genotypes A2/A2 were
      associated with significantly higher content of apoptotic white blood cells in
      comparison to relevant A2/A1 heterozygous genotypes (P<0.001,0.05) in lung cancer
      patients. These observations suggest that the p53 BstUI and the p53 MspI SNPs may
      play a certain role in p53 dependent apoptotic pathway.

PMID- 11844596
TI  - Outcome in patients with lung cancer found retrospectively to have had evidence
      of disease on past lung cancer mass screening roentgenograms.
AB  - This study enrolled 143 asymptomatic patients with lung cancer detected by mass
      screening during an 8-year period (January 1, 1993 to December 31, 2000) and who
      had received a lung cancer mass screening roentgenogram one year before the
      disease was found. There was no difference between the 5-year survival rates in
      patients with one-year delayed detection of lung cancer (n=62) and in patients
      without (n=81) (46 vs. 58%, log rank: P=0.1330, Wilcoxon: P=0.1008). However,
      according to the tumor size on the overlooked chest roentgenogram, the outcome in
      stage I+II patients with missed tumors >20 mm in dimension (n=20) was worse than
      those with missed tumors <10 mm (n=24) or those with missed tumors 10-20 mm
      (n=18) (40 vs. 82 or 81%, log rank: P=0.0047, Wilcoxon: P=0.0010). All missed
      tumors in the lung field that did not overlap thoracic components were <10 mm in
      dimension and appeared as patchy ground-glass opacities, and they could not have
      been recognized if there was no other information that the tumor developed in
      that location. This might also be related to the lack of mortality effectiveness
      of previous lung cancer mass screening problem. Although it may be difficult to
      find the tumors <10 mm on a chest roentgenogram on mass screening, one-year
      delayed detection of lung cancer < or = 20 mm will not affect the prognosis.

PMID- 11844597
TI  - Biological parameters on computed tomography guided fine needle aspiration biopsy
      from peripheral primary non-small cell lung cancer.
AB  - Computed tomography (CT) guided fine needle aspiration biopsy (CT-guided FNAB)
      represents the procedure of choice for diagnosing peripheral primary lung cancer
      before surgery. The aim of the present study was to assess the reliability of the
      immunocytochemical evaluation of biological parameters and DNA flow cytometry on
      cellular material obtained from non-small cell lung cancer (NSCLC) patients by CT
      guided FNAB. Thirty consecutive CT-guided FNABs obtained from NSCLC patients were
      submitted both to the immunocytochemical evaluation of p53, Ki67, bcl-2 and to
      flow cytometric DNA analysis. p53, Ki67 and bcl-2 were assessable in 60% (18/30),
      53% (16/30) and 48% (10/21) of the cases, respectively. Flow cytometric DNA
      analysis was performed in 19 out of the 30 cases and 74% (14/19) of the
      histograms were evaluable. Cytofluorimetric S-phase fraction (SPF), was obtained
      in 57% (8/14) of the cases. The results of the current study suggest that CT
      guided FNAB from primary NSCLC patients may represent an effective practice for
      the evaluation of biologic parameters and could be useful as a preoperative
      procedure. The role of neoadjuvant chemotherapy in operable NSCLC is still under
      debate. We suppose that in the future the presurgical characterization of NSCLC
      could suggest the opportunity of a neoadjuvant systemic treatment aimed to
      improve the clinical outcome. Moreover, in locally advanced or metastatic NSCLC
      immunocytochemistry could help to predict the response to chemotherapy and/or
      radiotherapy, avoiding ineffective treatments and supporting the development of
      more rational therapies.

PMID- 11844598
TI  - Expression of membrane-type-1-matrix metalloproteinase and metalloproteinase-2 in
      nonsmall cell lung carcinomas.
AB  - For the metastasis and invasion of cancer cells, destruction of extracellular
      matrix is essential. In this process, collagen is broken down by some matrix
      metalloproteinases. Matrix metalloproteinase 2 (MMP2) is able to cleave type IV
      collagen, and membrane-type-1-matrix metalloproteinase (MT1-MMP) induces
      activation of proMMP2. We investigated the expressions of MT1-MMP and MMP2 and
      their relation to both clinicopathologic parameters and clinical outcome in non
      small cell lung carcinomas (NSCLC). Eighty-nine specimens of NSCLC were examined
      using in situ hybridization and immunohistochemistry. Each metalloproteinase was
      expressed within the cytoplasm of tumor cells with or without stromal cells in
      NSCLC. Tumors in which tumor cells strongly stained for MT1-MMP mRNA or protein
      made up more than 50% of the tumor area were found in 44 and 26% of cases,
      respectively. The corresponding values for MMP-2 mRNA and protein, were 51 and
      26%. Our analysis of clinicopathological findings revealed a significant positive
      relationship between MT1-MMP mRNA and p-M. The correlation between MMP2 protein
      staining status and overall survival rate reached significance in the univariate
      analysis. However, an association was not demonstrated in the multivariate
      analysis. The detection of MT1-MMP and MMP2 is likely to be of limited value in
      informing the prognosis in NSCLC.

PMID- 11844599
TI  - Interlobar lymph node metastases according to primary tumor location in lung
      cancer.
AB  - Interlobar lymph node metastases were analyzed in consecutive 284 lung cancer
      patients with lobar-hilar and mediastinal lymph node dissection. Interlobar lymph
      node metastases were observed in 46 (16.2%) patients with no difference between
      right and left cases. On the right side, there was a significant difference in
      the frequency of inferior interlobar lymph node metastases between upper lobe and
      middle/lower lobe tumors (P=0.0004), but no difference in the frequencies of
      superior ones according to primary site. On the left, there was a significant
      difference in the frequency of interlobar lymph node metastases between upper
      lobe and lower lobe tumors (P=0.0021). In per-segment analyses, the frequency of
      inferior interlobar lymph node metastases in segments 1-3 and 6 was significantly
      lower than in the other total segments (P<0.0001) on the right, and that of
      interlobar lymph node metastases in the upper division segments (S1-3) was
      significantly lower than in the other total segments (P=0.0008) on the left. Even
      limited to one lobe, the patterns of interlobar lymph node metastases were
      different among the segments in the right lower lobe and the left upper lobe.

PMID- 11844600
TI  - Comorbidity in operable lung cancer: a multicenter descriptive study on 2992
      patients.
AB  - STUDY OBJECTIVES: To ascertain the frequency of diseases associated (comorbidity)
      with operable lung cancer (LC) globally, in relation to the presence of
      neoplastic clinical symptoms and age. DESIGN: Prospective; multi-institutional of
      19 Spanish hospitals. PATIENTS: Two thousand nine hundred and ninety two
      consecutive cases of LC, treated surgically by the Bronchogenic Carcinoma Co
      operative Group of the Spanish Society of Pneumology and Thoracic Surgery (GCCB
      S) between 1993 and 1997, are analysed. METHODS: At time of treatment, data on
      the presence or absence of different specific comorbidities in all consecutive
      patients operated on for LC were entered on identical forms at all hospitals of
      the GCCB-S. RESULTS: In 2189 patients (73%) there was one or several
      comorbidities (chronic obstructive pulmonary disease [COPD], systemic arterial
      hypertension, previous tumour, cardiac disease, peripheral vascular disease or
      diabetes). Fifty percent of the LC was associated to COPD; in 32% of these
      patients with COPD, preoperative measurement of FEV1 was 70% below the
      theoretical value. In comparing the cases with symptoms ascribable to LC, it was
      found that in asymptomatic patients the presence of a previous tumour, arterial
      hypertension or cardiac disease was significantly more frequent. Conversely, in
      symptomatic patients, COPD was significantly more frequent. The frequency of all
      evaluated comorbidities is significantly higher in the older age groups.
      CONCLUSIONS: In this multicenter study encompassing 2992 patients with operable
      LC, a high frequency of comorbidity has been found, COPD occurring most
      frequently. Certain diseases are more prevalent in asymptomatic patients,
      probably due to a screening bias. In older patients, there was a significant
      increase of all comorbidities.

PMID- 11844601
TI  - Surgical results of maximal local-regional treatment (cisplatin-enhanced high
      dose radiotherapy and adjuvant surgery) in initially non-resectable stage III
      lung cancer.
AB  - We report the surgical short- and long-term results in 42 patients treated in a
      phase II trial with 50-60 Gy cisplatin-enhanced radiotherapy (RT) and adjuvant
      resection, for initially non-resectable stage III non-small cell lung cancer. Six
      of the 42 patients had a complete response, 31 a partial response and five stable
      disease at the presurgical clinical restaging. A complete pathologic response was
      observed in 19 cases (R0a surgery); 15 complete resections were performed due to
      persistent disease (R0b). There were eight non-radical operations (R+). Operative
      deaths were seen after right pneumonectomy (five cases) and in case of a non
      radical operation after no response following the chemo-radiotherapy schedule
      (two cases). Surgery should be contraindicated in these cases. Overall eight-year
      survival was 26% (37% in R0a and 27% in R0b patients). No patient with R+ surgery
      survived at the eighth year. A local progression as initial failure occurred in
      four of the 34 R0 patients, and in five of the eighth with a R+ procedure.
      Resection seems to improve local control, but its role needs further definition.
      However, advanced stage III patients treated only with a local therapy were not
      precluded from a long-term survival.

PMID- 11844602
TI  - Radiation therapy for small-cell lung cancer: results of the 1995-1997 patterns
      of care process survey in Japan.
AB  - The Patterns of Care Study (PCS) conducted a nationwide audit survey in order to
      establish the national practice process of radiation therapy for small-cell lung
      cancer (SCLC) and examined the influence of institutional stratification on the
      process of care in Japan. The PCS randomly sampled institutions and patients
      using a two-stage cluster method and surveyed the process of radiation therapy
      for 174 stage I-III SCLC patients according to the category of institution,
      stratified as follows: A1, academic institutions treating > or = 300 patients a
      year; A2, <300 patients; B1, non-academic institutions treating > or = 120
      patients a year; and B2, <120 patients. Karnofsky performance status
      distributions showed significant variance by stratification of institutions
      (P=0.013). Patients treated on an outpatient basis accounted for 32% in A1, 23%
      in A2, 8% in B1, but only 5% in B2 (P=0.007). A photon energy > or = 10 MV was
      used for 87% of patients in A1, 69% in A2, 54% in B1 and 23% in B2 (P=0.001).
      Contralateral hilus was irradiated for 11% of patients in A1, 17% in A2, 29% in
      B1 and 3% in B2 (P=0.001). Field size reduction during the treatment course was
      done for 77% of patients in A1, 54% in A2, 60% in B1 and 42% in B2 (P=0.007).
      Ninety-two percent of patients received combined chemotherapy and radiation
      therapy, and the most frequently used drugs were etoposide (91%) and cisplatin
      (69%). The results of clinical studies on SCLC had favorably penetrated into the
      clinical practice. However, the stratification of institutions significantly
      affected the process of radiation therapy in Japan.

PMID- 11844604
TI  - Etoposide, ifosfamide and cisplatin (VIP) plus concurrent radiation therapy for
      previously untreated limited small cell lung cancer (SCLC): a Hoosier Oncology
      Group (HOG) phase II study.
AB  - Results of a previous Hoosier Oncology Group (HOG) study revealed a small
      survival advantage for VIP versus etoposide and cisplatin (EP) for patients with
      extensive stage small cell lung cancer (SCLC). This phase II study evaluated VIP
      with concurrent thoracic radiotherapy in patients with limited stage SCLC.
      Eligible patients had a Karnofsky Performance Score > or = 50, no prior
      chemotherapy or radiotherapy, and adequate end organ function. Fifty-three
      patients were entered. Radiotherapy was given as a daily fraction of 1.8 Gy, five
      fractions per week for 5 weeks for a total dose of 45 Gy, beginning on day 1 of
      VIP. The first 13 patients received etoposide 75 mg/m(2), cisplatin 20 mg/m(2),
      and ifosfamide 1.2 g/m(2) on days 1-4 with Mesna every 3 weeks for four cycles
      unless the patient demonstrated disease progression or undue toxicity. Excessive
      toxicity was seen in the first 13 patients; therefore, VIP was modified by
      deleting the 4th day for all subsequent patients. The major toxicity in this
      trial was myelosuppression. Grade 3/4 anemia, granulocytopenia, and
      thrombocytopenia occurred in 38, 75, and 34% of patients, respectively. There
      were four treatment-related deaths [three patients (23%) on the 4-day regimen and
      one patient (2.5%) on the 3-day regimen]. Twenty-five patients (47.2%) achieved a
      CR and 11 patients (20.8%) had a PR for an overall response rate of 68%. Minimum
      follow up for all patients is 5 years. Overall, 46 of 53 patients have died.
      Median, 1, 2 and 5 year overall survival for the entire group is 15.1 months,
      69.8, 35.9, and 13.2, respectively. The results of this phase II trial of VIP
      with concurrent early thoracic radiotherapy failed to demonstrate a superior
      response rate over other series utilizing EP. In addition, treatment-related
      morbidity and mortality appears to be unacceptably high with the VIP regimen.

PMID- 11844603
TI  - No thoracic radiation myelitis after spinal cord dose > or = 50.4 Gy using 1.2.
      Gy b.i.d. fractionation in patients with Stage III non-small cell lung cancer
      treated with hyperfractionated radiation therapy with and without concurrent
      chemotherapy.
AB  - We investigated a risk of developing radiation myelitis during four prospective
      studies using hyperfractionated radiation therapy (HFX RT) with and without
      concurrent chemotherapy (CHT) during which a portion of thoracic spinal cord
      received a dose > or = 50.4 Gy given via 1.2 Gy b.i.d. fractionation. Of 536
      patients with Stage III non-small cell lung cancer (NSCLC) which were treated on
      three prospective randomised Phase III studies and one Phase II study, 336
      patients received irradiation dose > or = 50.4 Gy to a portion of their spinal
      cord and survived >1 year after the beginning of therapy. None of these 336
      patients developed thoracic radiation myelitis. Therefore, the influence of
      potentially contributing factors on the occurrence of radiation myelitis, such as
      cord length, interfraction interval, or administration of concurrent CHT was not
      possible to investigate. These results give new insight about the influence of
      total dose/dose per fraction/interfraction interval with or without concurrent
      CHT on the thoracic spinal cord toxicity.

PMID- 11844605
TI  - Point mutations in the topoisomerase I gene in patients with non-small cell lung
      cancer treated with irinotecan.
AB  - Reverse transcription polymerase chain reaction (RT-PCR) single-strand
      conformation polymorphism analysis was used to detect topoisomerase I (top1)
      mutations in total RNA from 16 specimens that were excised during surgery from
      eight patients with non-small cell lung cancer (NSCLC) who had received
      preoperative chemotherapy consisting of irinotecan (CPT-11) and cisplatin. PCR
      single-strand conformation polymorphism and subsequent DNA sequencing analysis
      showed two nucleotide substitutions resulting in Trp736stop (TGG to TGA) and
      Gly737Ser (GGT to AGT) in one tumor specimen. The mutations were located near a
      site in top1 that was previously reported to harbor a mutation in the human lung
      cancer cell line PC7/CPT, which was selected for CPT resistance. These results
      demonstrate that mutations in top1 occur after chemotherapy with CPT-11 in NSCLC
      patients and suggest that development of resistance to CPT-11 in some patients
      may involve mutation of top1. However, the significance of top1 mutations to CPT
      resistance needs to be further investigated.

PMID- 11844606
TI  - Characterization of non-small-cell lung cancer cell lines established before and
      after chemotherapy.
AB  - We established several in vitro drug-resistant cell lines after continuous, long
      term exposure of each drug to elucidate mechanisms of drug resistance. Whether
      drug resistance in these in vitro resistant cell lines reflects clinical drug
      resistance still remains unanswered. In this study, a pair of lung cancer cell
      lines was established from one patient with squamous cell carcinoma of the lung,
      with one line being established before and one line after combination
      chemotherapy (cisplatin/ifosfamide/vindesine). Combination chemotherapy selected
      resistant EBC-2/R cells, which showed cross-resistance to 4-hydroxyifosfamide
      (3.2-fold), cisplatin (2.3-fold), and methotrexate (3.7-fold) and collateral
      sensitivity to vindesine (0.77-fold) compared with parent EBC-2 cells. EBC-2/R
      cells showed decrease in intracellular accumulation of cisplatin, increase in
      intracellular concentration of glutathione (GSH), and overexpression of multidrug
      resistance-associated protein (MRP) 3 when compared with EBC-2 cells. A single
      cycle of chemotherapy was not sufficient to select other mechanisms of drug
      resistance, such as multidrug resistance-1/P-glycoprotein, MRPs 1, 2, 4, and 5,
      lung resistance-related protein, metallothionein IIa, glutathione S-transferase
      pi, gamma-glutamylcysteine synthetase (light and heavy chain), and excision
      repair cross complementing 1. Sequentially we established two cell lines, which
      cell lines showed the differences of the cisplatin resistance, expression level
      of MRP3, intracellular GSH level and intracellular accumulation of cisplatin. A
      pair of cell lines will be useful to elucidate resistant mechanisms of cisplatin
      in heterogeneous lung cancer cells.

PMID- 11844607
TI  - Is weekly paclitaxel superior to paclitaxel given every 3 weeks? Results of a
      phase II trial.
AB  - Twenty-four patients previously treated with platinum containing regimens with
      stage IIIB-IV non-small-cell lung cancer (NSCLC) participated in the study.
      Sequential cohorts of patients were treated with 60 and 90 mg/m(2) of Paclitaxel
      per week. Paclitaxel was administered weekly over 1 h infusion for 6 consecutive
      weeks followed by 2 weeks without treatment (8-week cycle). A total of 252
      treatments were administered to the 24 patients. In 29 (12%) of 252 treatments
      grade 2 granulocytopenia was observed while four patients (17%) developed grade 2
      neuropathy. Seven patients (29%) achieved a partial response and five (21%) had
      stable disease. Paclitaxel 90 mg/m(2) per week as salvage treatment is well
      tolerated and has shown promising activity in patients with NSCLC who progress
      after platinum treatment.

PMID- 11844608
TI  - A 3-week schedule of gemcitabine plus cisplatin as induction chemotherapy for
      Stage III non-small cell lung cancer.
AB  - BACKGROUND: Our aim was to explore the activity and feasibility of gemcitabine
      plus cisplatin as induction chemotherapy in patients with Stage IIIA N(2) and
      selected IIIB non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: From
      September 1997 to July 2000, 70 chemonaive patients with Stage III NSCLC, median
      age of 64 years, World Health Organization performance status 0, 1, or 2, and the
      ability to tolerate a pneumonectomy entered the study and received gemcitabine
      1250 mg/m(2) on days 1 and 8 and cisplatin 70 mg/m(2) on day 2 every 3 weeks.
      After three cycles of induction chemotherapy, patients underwent resection or
      radiotherapy. RESULTS: Responses were seen in 40 of the 69 assessable patients,
      for an intent-to treat overall response rate of 57.1% (95% confidence interval,
      45-62%), with 4.2% complete response. Response rates were 68 and 35% in patients
      with Stage IIIA and IIIB disease, respectively. The overall pathological CR rate
      after induction chemotherapy was 3%, with an overall pathological downstaging
      rate of 20%. Median survival for all patients was 14.5 months, with an estimated
      1-year survival rate of 67% (95% CI, 54.3-79.5%). The estimated time to treatment
      failure was 12.6 months. Grade 3/4 thrombocytopenia was the main hematologic
      toxicity, occurring in 26% of patients, but was not associated with life
      threatening bleeding. Febrile neutropenia was rare and other severe non
      hematologic toxicities were uncommon. CONCLUSIONS: The 3-week schedule of
      gemcitabine plus cisplatin is highly active as induction chemotherapy in Stage
      IIIA N(2) unresectable NSCLC. This suggests a need for a multimodality approach
      upfront, such as concurrent chemoradiation therapy, particularly in patients with
      Stage IIIB disease.

PMID- 11844609
TI  - Interleukin-12 augments cytolytic activity of peripheral blood mononuclear cells
      against autologous lung cancer cells in combination with IL-2.
AB  - The majority of patients with advanced lung cancer die within a few years.
      Accordingly, new therapeutic modalities need to be developed. Interleukin (IL)-12
      was previously known as natural killer (NK) cell stimulatory factor or cytotoxic
      lymphocyte maturation factor. By virtue of its effects on T cells and NK cells,
      IL-12 seems to be one of the key cytokines that regulates cell-mediated anti
      tumor immune responses. Recently, there has been a substantial interest in the
      potential applications of IL-12 in the treatment of lung cancer. However, there
      have been no reports about the effect of IL-12 on peripheral blood mononuclear
      cells (PBMCs) obtained from lung cancer patients in an autologous setting. In
      this study, we examined the cytotoxicity of PBMC activated by IL-2, IL-12 or both
      against K562 or autologous lung cancer cells. In contrast to the effect of IL-2
      on NK activity, IL-12 alone augmented NK activity against K562 cells, but not
      against autologous lung cancer cells. IL-12 augmented the IL-2 mediated
      cytotoxicity of PBMC against both K562 and autologous lung cancer cells. In the
      absence of IL-2, IL-12 alone cannot induce an autologous anti-tumor effect in
      vivo. In summary, our results clearly demonstrated that IL-12 can augment the
      cytolytic activity of PBMC against K562 and autologous lung cancer cells when
      combined with IL-2, although, IL-12 alone was unable to induce a marked increase
      in the cytotoxicity against autologous lung cancer cells. These results suggest
      that an administration of IL-12 in combination with IL-2 may be a useful
      therapeutic option for solid tumors.

PMID- 11844610
TI  - Basaloid carcinoma, a rare primary lung neoplasm: report of a case and review of
      the literature.
AB  - Basaloid carcinoma of the lung is a rare primary neoplasm, first described in
      1992. Basaloid carcinoma is an aggressive subtype of Non small cell lung cancer,
      with poor 5-year survival, even in stage I and II resected tumors. Differential
      diagnosis from small cell, Neuroendocrine large cell and poorly differentiated
      squamous cell carcinoma is difficult to be made. We report a patient with lung
      basaloid carcinoma, initially diagnosed and treated as small cell carcinoma.
      Thoracotomy and resection of the tumor following chemotherapy, established the
      correct diagnosis.

PMID- 11844611
TI  - Lipid modification in mouse peritoneal macrophages after chronic cadmium
      exposure.
AB  - The effect of cadmium (Cd) exposure through drinking water on lipid status in
      mouse peritoneal macrophages (pM) was studied. After 2 months, adult male Balb/c
      mice that had drunk water with 15 ppm of Cd, showed tissue damage mediated by
      oxidative stress, as assessed by serum measuring of tissue damage and
      lipoperoxidation indicators. Resident pM obtained from Cd-exposed mice showed
      diminution in total lipids, total cholesterol, free cholesterol/esterified
      cholesterol ratio (FC/EC) and phospholipids in relation to control pM. On a
      percentage basis, the phospholipid composition showed that phosphatidylcholine
      (PC) and phosphatidylglycerol decreased, phosphatidylethanolamine (PE) increased,
      while phosphatidylinositol, sphingomyeline and phosphatidylserine did not change.
      The incorporation in vitro of [14C]-methyl-choline and [14C]-phosphorylcholine,
      as well as the activity of regulatory enzyme CTP-phosphocholine
      cytidylyltransferase, decreased in PC after 60 min. The incorporation of [14C]
      linoleic acid increased after 1 h and the incorporation of [14C]-ethanolamine
      increased after 90 min in PC. The incorporation in vitro of [3H]-cholesterol in
      total lipids decreased after 120 min of incubation. Besides, the stearic acid and
      arachidonic acid content increased, while the contents of palmitoleic acid and
      linoleic acid decreased. Chronic Cd exposure alters the lipid composition in
      resident pM of Balb/c mice.

PMID- 11844612
TI  - Chronic diazinon exposure: pathologies of spleen, thymus, blood cells, and lymph
      nodes are modulated by dietary protein or lipid in the mouse.
AB  - Little is known about the immunotoxicity of the organophosphate pesticide,
      diazinon. This study aims at detailing the pathologies in the thymus, spleen,
      blood cells, and lymph nodes (brachial, mesenteric, and hind quarter gluteal
      nodes) during chronic oral exposure (300 mg diazinonkg-1 food for 45 days), and
      explore the combined toxicity with excess dietary protein (40%) or lipid (20%
      corn oil). Animals were allowed to recover on normal food for 2 weeks. All
      experimental treatments caused organ pathologies, including necrotic degeneration
      of the trabeculae (spleen and thymus), hyperplasia of the cortex and medulla
      (thymus and lymph nodes), hyperplasia of white and red pulp (spleen), and
      sometimes haemorrhage (all tissues). Blood smears often showed
      crenated/hypochromic red cells and vacuolated white cells with abnormal nuclei.
      The severity of lesions during exposure was generally in the following order:
      lipid<protein<diazinon alone<protein plus diazinon<lipid plus diazinon. Post
      exposure recovery was limited, especially in the thymus and for lipid treatments.
      Quantitative image analysis revealed treatment and organ-specific changes in the
      proportions of fixed lymphocytes, PAS-positive carbohydrates, DNA, and protein
      staining. Histochemical changes were greatest after exposure. We conclude that
      the immunotoxicity of diazinon is exacerbated by excess dietary protein or lipid.
      The limited recovery and post-exposure histochemical changes imply deleterious
      effects on metabolism with oxidative stress after exposure.

PMID- 11844613
TI  - Application of the popliteal lymph node assay in immunotoxicity testing:
      complementation of the direct popliteal lymph node assay with flow cytometric
      analyses.
AB  - The popliteal lymph node assay (PLNA) has been proposed to measure the
      immunosensitizing potential of chemicals. The direct PLNA detects an
      immunomodulating effect but does not give insight into the mode of action of the
      chemical under test. Modifications of this test have been proposed, but they are
      difficult to perform in routine toxicity testing and require many animals. In the
      present investigation the direct PLNA was extended with the flow cytometric
      determinations of: (a) lymphoblasts; (b) the phenotyping of lymphoid
      subpopulations; (c) the determination of expression of proliferation/activation
      markers CD25, CD69 and CD62L/CD44 and (d) the analysis of intracellular cytokines
      interferon gamma, interleukin 2 and interleukin 4. Streptozotocin, hydrazine,
      HgCl2 and trinitrobenzene sulfonic acid were used as model chemicals. The
      different mode of action of these substances was well documented by the
      techniques applied. As the proposed flow cytometric methods can easily be
      performed and do not require additional test animals this complementation of the
      direct PLNA seems a promising approach in immunotoxicity testing.

PMID- 11844614
TI  - Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on T cell-derived cytokine
      production in ovalbumin (OVA)-immunized C57Bl/6 mice.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is known to suppress both cellular and
      humoral immunity. Effector T cell-derived type-2 cytokines, including IL-4 and IL
      5, play pivotal roles in humoral immunity. Herein, we studied whether TCDD
      affects type-2 cytokine productions during the immune response. C57Bl/6 mice were
      intraperitoneally immunized with ovalbumin (OVA) and orally administered 5 or 20
      microg TCDD/kg on Day 0, and then challenged with OVA on Day 21. Seven days later
      (Day 28), antigen-specific antibodies in plasma, and T cell-derived cytokines
      produced by splenocytes and proliferation of splenocytes upon ex vivo re
      stimulation with OVA were investigated. The quantities of IgM class and IgG1
      class OVA-specific antibodies in plasma were reduced by 5 or 20 microg TCDD/kg
      and by 20 microg TCDD/kg, respectively. While thymus weight and cellularity were
      reduced by 20 microg TCDD/kg, spleen weight and cellularity were not changed by
      either 5 or 20 microg TCDD/kg. The proportions of B and T cells in the spleen
      were not affected by TCDD exposure. On the other hand, splenocytes from mice
      treated with 5 or 20 microg TCDD/kg were shown to produce less IL-4 or IL-5 upon
      ex vivo re-stimulation with OVA. Production of the T cell growth factor IL-2 was
      also decreased in splenocytes from TCDD-treated mice. In contrast, the type-1
      cytokine IFN-gamma was increased by TCDD. Twenty micrograms of TCDD/kg suppressed
      OVA- or T cell mitogen (Con A)-stimulated proliferation of splenocytes, but did
      not affect B cell mitogen (LPS)-stimulated proliferation. These results suggested
      compromised T cell activation and suppressed type-2 cytokine production by T
      cells to be involved in the impaired humoral immunity associated with TCDD
      exposure.

PMID- 11844615
TI  - Immunotoxicological investigation in rats dosed repeatedly with combinations of
      cypermethrin, As(III), and Hg(II).
AB  - The effects of the combined exposure of cypermethrin (CY), NaAsO2 (As), and HgCl2
      (Hg) were investigated in male Wistar rats following 4 weeks of oral exposure.
      Standard toxicological (body weight gain, organ weights of brain, thymus, heart,
      lung, liver, kidneys, adrenals, testes, and popliteal lymph node), haematological
      (white blood cell, red blood cell, haematocrit, MCV-mean volume of red blood
      cells, and cell content of the femoral bone marrow), and immune function (IgM-PFC
      response, delayed type hypersensitivity (DTH) reaction) parameters were measured.
      The two doses selected for the combination were: a high (H) dose equal to lowest
      observed effect level determined in preliminary experiments (CY(H)=55.4 mg/kg,
      As(H)=13.3 mg/kg, Hg(H)=3.20 mg/kg), and a low (L) dose which was ineffective
      (non-observed effect level); CY(L)=11.1 mg/kg, As(L)=3.33 mg/kg, Hg(L)=0.40
      mg/kg). CY(H) was combined with As(L) or Hg(L), and the H doses of the heavy
      metals were combined with CY(L). Beside vehicle control, the H dose components of
      the combinations were also used as internal controls. The main finding of this
      study was that certain combinations, when compared to H dose internal control,
      significantly altered the body weight gain (As(H)+CY(L)), the relative weight of
      adrenals and popliteal lymph node (CY(H)+As(L) and CY(H)+Hg(L)), the cell content
      of the femoral bone marrow (CY(H)+Hg(L)), and the time course of DTH reaction
      (CY(H)+As(L)). According to the present results, combined exposure with CY and
      the heavy metals investigated can modify the toxicity and/or the functional
      detection limit of the single substances.

PMID- 11844616
TI  - Acute effects of ozone exposure on lung function in mice sensitized to ovalbumin.
AB  - Pulmonary responses to ozone exposure (1.0 ppm) were investigated in mice
      sensitized to ovalbumin compared with control mice receiving saline. Pulmonary
      function parameters were measured by pneumotachography. Arterial blood gases and
      the concentrations of soluble intercellular adhesion molecule-1 (sICAM-1) and
      tumor necrosis factor-alpha (TNF-alpha) in bronchoalveolar lavage fluid were
      analyzed. Ozone exposure, when compared with filtered air exposure, caused
      significantly larger decreases in dynamic compliance (P<0.05) and minute
      ventilation (P<0.05) in ovalbumin-sensitized mice but not in control mice.
      Moreover, the decrease in minute ventilation in response to ozone exposure was
      significantly greater (P<0.01) in ovalbumin-sensitized mice than in control mice.
      Ozone exposure caused a significant decrease in PaO2 in ovalbumin-sensitized mice
      but not in control mice. PaO2 after ozone exposure tended to be smaller in
      ovalbumin-sensitized mice than in control mice. The concentration of sICAM-1 in
      bronchoalveolar lavage fluid increased in ovalbumin-sensitized mice, but effects
      of ozone exposure were not observed. These results indicated that sensitization
      of the immune system to ovalbumin might be a risk factor which aggravates the
      effects of ozone exposure on the respiratory system.

PMID- 11844617
TI  - Expression of the mouse Fc receptor B2 in bovine cells rescues the infectivity of
      conditionally neutralized bovine viral diarrhea virus.
AB  - We examined the infectivity of bovine viral diarrhea virus (BVDV) particles
      opsonized with monoclonal antibodies on bovine cells expressing the murine
      Fcgamma receptor B2 (FcgammaRB2). Incubation of BVDV with each of five monoclonal
      antibodies (Mabs) to the envelope glycoprotein E2 led to efficient virus
      neutralization, as evidenced by the failure to infect standard bovine testicle
      cells. In contrast, inoculation of four of these Mab-virus complexes onto
      transfectant bovine testicle cells expressing FcgammaRB2 resulted in a
      significant rescue of virus infectivity. Mab-virus complexes were 13.1, 7.37,
      5.56 and 4.49 times more infectious for FcgammaR-expressing cells than for cells
      lacking FcgammaR. Because Mab-opsonized BVDV virion complexes uninfectious for
      standard cells may initiate productive infection in cells expressing the
      FcgammaR, the virion-Mab interaction should be described as a conditional
      neutralization. Interestingly, the infectivity of BVDV complexed with a specific
      virus neutralizing Mab (10f9) could not be rescued in FcgammaRB2-expressing
      cells. We postulate that attachment of antibody-virus complexes to FcR may only
      result in productive infection if the binding of antibody to virions does not
      interfere with post-attachment entry functions. Conditionally neutralized virions
      may play a role in the pathogenesis of any of the multiple diseases resulting
      from BVDV infections in cattle.

PMID- 11844618
TI  - Genetic evolution of Mycoplasma capricolum subsp. capripneumoniae strains and
      molecular epidemiology of contagious caprine pleuropneumonia by sequencing of
      locus H2.
AB  - Contagious caprine pleuropneumonia (CCPP) is a major threat to goat farming in
      developing countries. Its exact distribution is not well known, despite the fact
      that new diagnostic tools such as PCR and competitive ELISA are now available.
      The authors developed a study of the molecular epidemiology of the disease, based
      on the amplification of a 2400 bp long fragment containing two duplicated gene
      coding for a putative membrane protein. The sequence of this fragment, obtained
      on 19 Mycoplasma capricolum subsp. capripneumoniae (Mccp) strains from various
      geographical locations, gave 11 polymorphic positions. The three mutations found
      on gene H2prim were silent and did not appear to induce any amino acid
      modifications in the putative translated protein. The second gene may be a
      pseudogene not translated in vivo, as it bore a deletion of the ATG codon found
      in the other members of the "Mycoplasma mycoides cluster" and as the six
      mutations evidenced in the Mccp strains would induce modifications in the
      translated amino acids. In addition, an Mccp strain isolated in the United Arab
      Emirates showed a deletion of the whole pseudogene, a further indication that
      this gene is not compulsory for mycoplasma growth. Four lineages were defined,
      based on the nucleotide sequence. These correlated relatively well with the
      geographical origin of the strains: North, Central or East Africa. The strain of
      Turkish origin had a sequence similar to that found in North African strains,
      while strains isolated in Oman had sequences similar to those of North or East
      African strains. The latter is possibly due to the regular import of goats of
      various origins. Similar molecular epidemiology tools have been developed by
      sequencing the two operons of the 16S rRNA gene or by AFLP. All these various
      techniques give complementary results. One (16S rRNA) offers the likelihood of a
      finer identification of strains circulating in a region, another (H2) of
      determining the geographical origin of the strains. These tools can make a very
      useful contribution to understanding the epidemiology of CCPP.

PMID- 11844619
TI  - O-serogroups, eae gene and EAF plasmid in Escherichia coli isolates from cases of
      bovine mastitis in Brazil.
AB  - Mastitis has been recognized for some time as the most costly disease in dairy
      herds. From March 1997 to August 1998, 2144 samples of bovine mastitic milk were
      collected, from which 182 Escherichia coli isolates were made, and from which 141
      isolates had the somatic antigen (serogroup) determined. Twelve different
      serogroups were isolated from mastitic milk, and among them were O26, O55, O111
      and O119, all of them classic enteropathogenic E. coli (EPEC) serogroups. These
      represented 40.0% of the isolates. The 20 of 57 isolates tested had plasmids and
      in dot blot hybridization, nine isolates were positive for an EaeA probe and an
      EPEC adherence factor (EAF) probe while two isolates were negative for EaeA probe
      but positive for the EAF probe. The nine isolates were characterized as attaching
      and effacing (A/E) E. coli (AEEC) isolates.

PMID- 11844620
TI  - Phenotypic and genetic characterisation of bacteriocin-producing strains of
      Staphylococcus aureus involved in bovine mastitis.
AB  - Fifty strains of Staphylococcus spp. isolated from bovine mastitis cases in
      several herds from different Argentinian provinces were screened for
      antimicrobial substances. Twelve strains exhibited a high antagonistic activity
      against the indicator strain (Corynebacterium fimi) and were chosen for further
      characterisation. The antimicrobial substances were sensitive to proteolytic
      enzymes suggesting that they might be bacteriocins (Bac). These strains were
      identified as S. aureus by the amplification of the femA gene. Plasmid profile
      analysis of these strains revealed the presence of at least one plasmid. Eleven
      strains carried a plasmid with a size similar to that of pRJ6 (8.0kb), which
      encodes aureocin A70, a bacteriocin produced by the Brazilian S. aureus strain
      A70 isolated from commercial milk. The other strain harboured a much larger
      plasmid. PCR experiments, using specific primers for amplification of the
      bacteriocin operon found in pRJ6, showed that all strains had the expected 525bp
      amplicon, suggesting that the bacteriocin produced may be related to aureocin
      A70. The genomic DNA of all Bac(+) strains was then analysed by pulsed-field gel
      electrophoresis (PFGE) in order to investigate clonal relationships amongst
      strains. Based on the results of PFGE experiments, 10 out of the 12 Bac(+)
      strains belonged to the same clone. The remaining two strains are possibly
      related to the prevalent clone. The aureocin A70 producer-strain belonged to a
      distinct clone.

PMID- 11844621
TI  - Subspecies variation in Greek strains of Chlamydophila abortus.
AB  - The Greek chlamydial strains FAS, FAG, VPG and LLG, isolated from aborted sheep
      or goat foetuses, had been previously characterized as divergent on the basis of
      mouse cross-protection experiments, with LLG and its homologous POS significantly
      different from the rest in inclusion morphology, polypeptide profiles and
      reactivity with monoclonal antibodies. To determine the genetic basis of their
      divergence the 16S-23S ribosomal intergenic spacer was analysed by RFLP analysis
      of PCR 16SF2/23R amplicons. Using the restriction enzymes BfaI, SfcI, HpaI, BclI,
      DdeI and AclI, the strains were classified as Chlamydophila abortus. However,
      digestion with RsaI made it possible to differentiate strains FAS, FAG and VPG
      from strains LLG and POS, generating DNA fragments of 530/55 and 585bp,
      respectively. By subsequent sequence analysis of the 23S domain I rRNA gene only
      strain FAS was identical to reference strain A22 of C. abortus. Strains FAG and
      VPG presented an identical nucleotide deviation at position 593 of signature
      sequences. Strains LLG and POS presented three identical nucleotide deviations at
      positions 156, 186 and 307. Variation within the domain I signature sequences for
      the examined abortion strains was < or =0.69%. In conclusion, substantial genetic
      and biological diversity among strains of C. abortus was demonstrated, suggesting
      that subspecies variation status for certain strains may be applicable. Our
      findings suggest that differentiation may be possible at a subspecies level by
      RFLP analysis.

PMID- 11844622
TI  - Prevalence and diversity of Arcobacter spp. isolated from the internal organs of
      spontaneous porcine abortions in Denmark.
AB  - A study was conducted to determine the prevalence and possible significance of
      campylobacteria in pig abortions in Denmark. Surface-cauterised liver and kidney
      samples from 55 aborted pig fetuses submitted to the Danish Veterinary Laboratory
      were taken and a sensitive isolation procedure used to examine pooled tissue
      samples for Campylobacter, Arcobacter and Helicobacter spp. Routine
      microbiological, immunological, and histopathological examinations were also
      performed to identify concurrent infections or histopathological changes. The
      abortions tested negative for established abortifacient pathogens (Brucella,
      Leptospira, PPV, PRRSV), but Arcobacter spp. were recovered from 23/55 abortions.
      Co-infections with Streptococcus suis, Escherichia coli, and haemolytic
      streptococci were observed in 7/23 Arcobacter-positive fetuses, and in 4/32
      Arcobacter-negative fetuses. Histopathological analyses identified placentitis,
      pneumonia, hepatitis and encephalitis among the study group. However, no obvious
      pathologic features were solely associated with Arcobacter-positive cases, nor
      were Arcobacter-like bacteria observed in tissue samples. Protein profile
      analyses of the 27 Arcobacter isolates identified 11 as A. cryaerophilus and 10
      as A. skirrowii. Six strains could not be classified into any existing species
      and were phenotypically distinct, thus, potentially representing at least one new
      species. The identification results showed that multiple taxa could be found in a
      single fetus, and in distinct aborted fetuses from a single sow. The high
      prevalence of arcobacters in Danish pig abortions may account for at least some
      of the >90% of cases in which no established abortifacient agent is detected, but
      further studies are needed to define the role of each species, especially where
      co-infections with other bacteria are present.

PMID- 11844623
TI  - Prevalence of serogroups and virulence genes in Escherichia coli associated with
      postweaning diarrhoea and edema disease in pigs and a comparison of diagnostic
      approaches.
AB  - Identification of Escherichia coli causing porcine postweaning diarrhoea (PWD) or
      edema disease (ED) requires knowledge regarding the prevalent pathotypes within a
      given region. This study was undertaken to determine the present distribution of
      serogroups, hemolytic activity and virulence factor gene profiles among porcine
      pathogenic E. coli isolates in Denmark and to compare detection of these
      characteristics as diagnostic approaches. Five hundred and sixty-three E. coli
      were serogrouped using E. coli O-antisera and investigated for hemolytic
      activity. Of these, 219 isolates were further characterized using a 5'-nuclease
      PCR assay detecting genes for adhesion factors, enterotoxins and verocytotoxin 2e
      (VT2e). Forty-two different serogroups were found. The most prevalent serogroup
      was O149 accounting for 49.9% of all isolates, followed by O138 (14.9%), O139
      (6.9%), O141 (4.1%) and O8 (3.7%). Hemolytic activity was detected in 87.7% of
      all isolates. Virulence factor genes detected were F4 (44.7%), F18 (39.3%),
      intimin (1.4%), F6 (0.9%), STb (77.6%), EAST1 (65.8%), LT (61.6%), STa (26.5%)
      and VT2e (16.4%). Six pathotypes accounted for 65.7% of all isolates
      investigated. Using possession of virulence factor genes as reference, O
      serogrouping employing a selection of antisera representing common pig pathogenic
      serogroups and detection of hemolysis were evaluated as epidemiological markers
      for pathogenicity. Both criteria were associated with pathogenicity (P<0.001, for
      both), however, both methods also resulted in false classifications regarding
      pathogenicity for 11.9 and 13.2% of isolates, respectively. Detection of adhesion
      factor genes F4, F18 and intimin is suggested as an operational alternative when
      diagnosing PWD and ED.

PMID- 11844624
TI  - Identification of the crayfish plague fungus Aphanomyces astaci by polymerase
      chain reaction and restriction enzyme analysis.
AB  - To characterise the DNA of the crayfish plague fungus Aphanomyces astaci,
      Saprolegniales (Oomycetes), primers were developed to amplify a 1050bp segment of
      the 28S rDNA region. Restriction enzymes were applied to the amplicon obtained,
      to distinguish A. astaci from 12 fungal species belonging also to the
      Saprolegniales and five more distantly related fungi. Most of the fungal species
      included in the study are either known parasites of freshwater crayfish cuticle
      or can be found in their natural environment. A. astaci DNA was distinguishable
      from the DNA of other fungal species tested by using the primers developed plus
      restriction enzymes AluI, HindIII and AvaI. Prior to this study, methods for A.
      astaci-species determination, e.g. spore production and infection experiments,
      required a protracted period to yield results; the method described in this study
      is quicker.

PMID- 11844625
TI  - Tolerance issues in the use of somatostatin analogs in palliative care.

PMID- 11844626
TI  - Prolonged sensory and motor deficit following short-term lumbar epidural
      analgesia in a patient with mixed connective tissue disease.

PMID- 11844627
TI  - Clinical pharmacists' pain consult service in a community hospital.

PMID- 11844628
TI  - Palliative care teams: self-reflection - past, present, and future.

PMID- 11844629
TI  - Do hospital-based palliative teams improve care for patients or families at the
      end of life?
AB  - To determine whether hospital-based palliative care teams improve the process or
      outcomes of care for patients and families at the end of life, a systematic
      literature review was performed employing a qualitative meta-synthesis and
      quantitative meta-analysis. Ten databases were searched. This was augmented by
      hand searching specific journals, contacting authors, and examining the reference
      lists of all papers retrieved. Studies were included if they evaluated palliative
      care teams working in hospitals. Data were extracted by two independent
      reviewers. Studies were graded using two independent hierarchies of evidence. A
      Signal score was used to assess the relevance of publications. Two analyses were
      conducted. In a qualitative meta-synthesis data were extracted into standardized
      tables to compare relevant features and findings. In quantitative meta-analysis
      we calculated the effect size of each outcome (dividing the estimated mean
      difference or difference in proportions by the sample's standard deviation). Nine
      studies specifically examined the intervention of a hospital-based palliative
      care team or studies. A further four studies considered interventions that
      included a component of a hospital or support team, although the total
      intervention was broader. The nature of the interventions varied. The studies
      were usually in large teaching hospitals, in cities, and mainly in the United
      Kingdom. Outcomes considered symptoms, quality of life, time in hospital, total
      length of time in palliative care, or professional changes, such as prescribing
      practices. Only one of the studies was a randomized controlled trial and this
      considered a hospital team as part of other services. Most method scores
      indicated limited research quality. Comparison groups were subject to bias and
      the analyses were not adjusted for confounding variables. In addition, there were
      problems of attrition and small sample sizes. Nevertheless, all studies indicated
      a small positive effect of the hospital team, except for one study in Italy,
      which documented deterioration in patient symptoms. The Signal scores indicated
      that the studies were relevant. No study compared different models of hospital
      team. This review suggests that hospital-based palliative care teams offer some
      benefits, although this finding should be interpreted with caution. The study
      designs need to be improved and different models of providing support at the end
      of life in hospital need comparison. Standardized outcome measures should be used
      in such research and in practice.

PMID- 11844630
TI  - Increased plasma morphine metabolites in terminally ill cancer patients with
      delirium: an intra-individual comparison.
AB  - Delirium often causes severe distress for terminally ill cancer patients, and
      treatment of underlying pathologies is important to achieve symptom alleviation.
      Although accumulation of morphine metabolites may play an important role in
      development of delirium, empirical findings are conflicting due to a large inter
      individual variation in morphine-related concentrations. To explore intra
      individual changes of morphine metabolite concentrations before and after
      occurrence of terminal delirium, a prospective observational study was performed
      on terminally ill cancer patients. Among 131 consecutive hospice inpatients, 16
      samples from 8 patients who received two blood samplings before and after
      development of delirium were analyzed. Delirium developed a median of 5 days
      before death, and clinical causes were attributed to multi-organ failure. Plasma
      concentrations of morphine-6-glucuronide (M-6-G) and morphine-3-glucuronide (M-3
      G) significantly increased after development of delirium within the same patient.
      Mean normalized concentrations of M-6-G and M-3-G elevated from 1.24 +/- 1.06 to
      2.94 +/- 3.52 ng/mL/mg (P = 0.016), and from 7.46 +/- 4.75 to 15.4 +/- 13.2
      ng/mL/mg (P = 0.016), respectively. Normalized morphine concentration increased
      with a marginal statistical significance from 0.54 +/- 0.27 to 0.83 +/- 0.22
      ng/mL/mg (P = 0.055). In conclusion, plasma concentrations of M-6-G and M-3-G
      were significantly higher after development of terminal delirium than before. It
      is suggested that accumulations of morphine metabolites can contribute to
      development of delirium in cancer patients whose death is impending.

PMID- 11844631
TI  - Assessment of sickle cell pain in children and young adults using the adolescent
      pediatric pain tool.
AB  - The objectives of this study were to describe and compare the characteristics of
      pain experienced by children and young adults with sickle cell disease (SCD) in
      inpatient and outpatient settings. The Adolescent Pediatric Pain Tool (APPT), a
      multidimensional self-report pain assessment, was completed by African American
      children and young adults (mean age 15.39 +/- 4.32) with SCD during a clinic
      visit (n = 52), day hospital visit (n = 29), or during the first 24 hours of an
      inpatient stay (n = 72). Multiple linear regression revealed that pain intensity,
      number of body areas with pain, and the quality of pain were related to age, sex,
      and care setting. Pain intensity, location, and quality were of greater magnitude
      than previous reports of early postoperative pain in children. Examining the
      specific dimensions of pain intensity, location, and quality and the influencing
      factors of age, sex, and care setting may lead to more effective treatments for
      SCD pain.

PMID- 11844632
TI  - Combination analgesic efficacy: individual patient data meta-analysis of single
      dose oral tramadol plus acetaminophen in acute postoperative pain.
AB  - The primary aims of this study were to assess the analgesic efficacy and adverse
      effects of single-dose oral tramadol plus acetaminophen in acute postoperative
      pain and to use meta-analysis to demonstrate the efficacy of the combination drug
      compared with its components. Individual patient data from seven randomized,
      double blind, placebo controlled trials of tramadol plus acetaminophen were
      supplied for analysis by the R.W. Johnson Pharmaceutical Research Institute,
      Raritan, New Jersey, USA. All trials used identical methods and assessed single
      dose oral tramadol (75 mg or 112.5 mg) plus acetaminophen (650 mg or 975 mg) in
      adult patients with moderate or severe postoperative pain. Summed pain intensity
      and pain relief data over six and eight hours and global evaluations of treatment
      effect after eight hours were extracted. Number-needed-to-treat (NNT) for one
      patient to obtain at least 50% pain relief was calculated. NNTs derived from pain
      relief data were compared with those derived from pain intensity data and global
      evaluations. Information on adverse effects was collected. Combination analgesics
      (tramadol plus acetaminophen) had significantly lower (better) NNTs than the
      components alone, and comparable efficacy to ibuprofen 400 mg. This could be
      shown for dental but not postsurgical pain, because more patients were available
      for the former. Adverse effects were similar for the combination drugs and the
      opioid component alone. Common adverse effects were dizziness, drowsiness,
      nausea, vomiting, and headache. In sum, this meta-analysis demonstrated analgesic
      superiority of the combination drug over its components, without additional
      toxicity.

PMID- 11844633
TI  - Chronic pain prevalence and analgesic prescribing in a general medical
      population.
AB  - In order to better understand the prevalence of chronic pain and the frequency of
      analgesic use in the U.S. veteran general medical population, a review of 300
      randomly selected charts was conducted. This review revealed that 50% of patients
      suffered from at least one type of chronic pain. A review of the corresponding
      pharmacy records indicated that approximately 75% of patients with chronic pain
      were prescribed at least 1 analgesic, and most received 2 or more. While
      nonsteroidal anti-inflammatory drugs were the most commonly prescribed class of
      analgesics, 44% of those receiving an analgesic received opioids. Examination of
      clinic notes revealed that the prescribing physicians documented physical
      examination infrequently, and commented on a specific opioid treatment plan or
      follow-up of that plan in a minority of cases. It appears that chronic pain is
      common among U.S. veterans, and that analgesics, including opioids, are commonly
      prescribed. Documentation of the efficacy of opioids for treating chronic pain is
      often scant.

PMID- 11844634
TI  - Pain management, controlled substances, and state medical board policy: a decade
      of change.
AB  - Physicians' concerns about regulatory scrutiny and the possibility of unwarranted
      investigation by regulatory agencies negatively affect their prescribing of
      opioid analgesics to treat pain. Indeed, some state medical boards have rejected
      prescribing practices that are considered acceptable by today's standards. This
      article describes a ten-year program of research, education, and policy
      development implemented by the Pain & Policy Studies Group aimed at updating and
      clarifying state medical board policies on the use of opioid analgesics to treat
      pain, including cancer and chronic noncancer pain. Following surveys of medical
      board members and educational workshops, state medical board policies began an
      initial period of change, drawing on guidelines from other states, particularly
      in California. The next phase of policy development was marked by the
      introduction of Model Guidelines by the Federation of State Medical Boards of the
      U.S. The Model Guidelines address professional standards for the appropriate
      prescribing of opioid analgesics for pain management, as well as physicians'
      fears of regulatory scrutiny. Although most state medical boards have adopted
      regulations, guidelines, or policy statements relating to controlled substances
      and pain management, to date ten boards have adopted the Model Guidelines, while
      ten more have adopted the Model Guidelines in part. Further actions are
      recommended so that state medical boards can address inadequate pain management
      and physician concerns about regulatory scrutiny.

PMID- 11844635
TI  - Methadone and fluconazole: respiratory depression by drug interaction.
AB  - A 60-year-old man with advanced gastric cancer achieved good pain control on a
      stable dose of methadone for 10 days. However, he developed respiratory
      depression 2 days after intravenous fluconazole was administrated for refractory
      oral candidiasis. Intravenous naloxone effectively reversed the respiratory
      depression. This case illustrates a significant interaction between methadone and
      fluconazole, and highlights the need for awareness of potential interactions
      between drugs used in palliative care.

PMID- 11844636
TI  - Neurogenic pulmonary edema in palliative care.
AB  - Neurogenic pulmonary edema may be a complication of the terminal phase of
      cerebral tumors. Clinically, it is likely to be considered the "death rattle" and
      is likewise very distressing to attending relatives. Positional change tends to
      aggravate neurogenic pulmonary edema but not the "death rattle." Its occurrence
      may be an indication for sedation for the intractable distress of the dying
      patient.

PMID- 11844637
TI  - Nebulized fentanyl citrate improves patients' perception of breathing,
      respiratory rate, and oxygen saturation in dyspnea.
AB  - Dyspnea, a subjective symptom of impaired breathing, occurs in 70% of terminally
      ill cancer patients. Current treatments are suboptimal and little is known about
      the patient's perception of effect. We tested nebulized inhaled fentanyl citrate
      on patient perceptions, respiratory rate, and oxygen saturation. The study was
      conducted using a convenience sample of 35 cancer patients on a dedicated
      oncology unit. We assessed patient perception (did breathing stay the same,
      worsen, or improve), respiratory rate, and oxygen saturation by pulse oximetry at
      baseline, 5 minutes, and 60 minutes. Twenty-six of 32 (81%) patients reported
      improvement in breathing, 3 (9%) were unsure, and 3 (9%) reported no improvement.
      Oxygen saturation improved from 94.6% at baseline to 96.8% at 5 minutes and 96.7%
      at 60 minutes (P = 0.0069 compared to baseline). Respiratory rates improved from
      a baseline of 28.4/min to 25.9/min at 5 minutes and 24.1/min at 60 minutes (P =
      0.0251 compared to baseline). No side effects were observed. Inhaled nebulized
      fentanyl citrate significantly improved patient perception of breathing,
      respiratory rate, and oxygen saturation. This inexpensive and readily available
      treatment may offer substantial relief of end-of-life dyspnea. Randomized trials,
      dose, and length of effect trials are underway.

PMID- 11844639
TI  - Low dose ketamine as an analgesic adjuvant in difficult pain syndromes: a
      strategy for conversion from parenteral to oral ketamine.
AB  - Ketamine is a non-competitive N-methyl D-aspartate (NMDA) receptor antagonist
      with analgesic and dissociative anesthetic properties. Low dose or sub-anesthetic
      doses of ketamine have been used effectively as either a primary analgesic or
      analgesic adjuvant in a variety of pain syndromes. In this paper, three patients
      with difficult to treat, predominantly neuropathic pain syndromes will be
      described. Their pain syndromes were initially managed successfully with the
      addition of low dose parenteral ketamine as an analgesic adjuvant. The strategy
      of concurrently starting ketamine at a low dose, i.e., 40-60 mg over 24 hours,
      with a benzodiazepine proved effective in preventing psychotomimetic side
      effects. An unavoidable shortage of ketamine prompted a literature search, which
      suggested that the equianalgesic dose of oral ketamine could be lower than the
      parenteral dose. Subsequently the patients were converted to oral ketamine at
      doses 30 to 40% of the previous parenteral dose. Their pain syndromes remained
      controlled on the lower dose of oral ketamine with remarkably few side effects.
      The implications of this warrant further discussion and study.

PMID- 11844640
TI  - Audio-visual communication and its use in palliative care.
AB  - The technology of telemedicine has been used for over 20 years, involving
      different areas of medicine, providing medical care for the geographically
      isolated patients, and uniting geographically isolated clinicians. Today audio
      visual technology may be useful in palliative care for the patients lacking
      access to medical services due to the medical condition rather than geographic
      isolation. We report results of a three-month trial of using audio-visual
      communications as a complementary tool in care for a complex palliative care
      patient. Benefits of this system to the patient included 1) a daily limited
      physical examination, 2) screening for a need for a clinical visit or admission,
      3) lip reading by the deaf patient, 4) satisfaction by the patient and the
      caregivers with this form of communication as a complement to telephone
      communication. A brief overview of the historical prospective on telemedicine and
      a listing of applied telemedicine programs are provided.

PMID- 11844638
TI  - Changing M3G/M6G ratios and pharmacodynamics in a cancer patient during long-term
      morphine treatment.
AB  - A cancer patient receiving long-term oral sustained-release morphine treatment
      and periodically presenting with unusually high plasma M3G/M6G ratios is
      described. We found the patient's formation of M6G more unstable and perhaps
      delayed compared to the formation of M3G. There is no apparent explanation for
      this phenomenon and the high M3G/M6G ratios had no implications for the patient's
      pain experience or side effects from the morphine treatment.

PMID- 11844641
TI  - Is glutamine beneficial in ischemic heart disease?
AB  - OBJECTIVE: Glutamine enhances recovery from acute normothermic ischemia in
      isolated rat heart by a dose-dependent effect (Khogali et al. J Mol Cell Cardiol
      1998;30:819). We compared the cardioprotective effects of equimolar
      concentrations of glutamine, glutamate, and aspartate in isolated rat heart. We
      also explored the potential cardioprotective effects of glutamine in patients
      with chronic stable angina. METHODS: The isolated perfused working rat heart was
      subjected to ischemia, followed by reperfusion with or without an amino acid (2.5
      mM). Patients with chronic stable angina received a single oral dose of glutamine
      (80 mg/kg) or placebo in a double-blind, random fashion 40 min before a standard
      Bruce exercise test. RESULTS: Postischemic reperfusion of isolated rat heart with
      glutamine (but not with glutamate or aspartate) resulted in full recovery of
      cardiac output. Only glutamine prevented the decrease in the myocardial ratio
      between adenosine triphosphate to adenosine diphosphate and significantly
      enhanced the myocardial ratio of reduced to oxidized glutathione. A single oral
      dose of glutamine given to patients with chronic stable angina significantly
      increased plasma glutamine concentration from 419 to 649 microM and delayed time
      to onset of more than 1.0 mm of ST segment depression on the ECG by 38 s.
      CONCLUSION: Glutamine may be cardioprotective in patients with coronary heart
      disease.

PMID- 11844642
TI  - Glutamine supplementation and GH/IGF-I treatment in critically ill patients:
      effects on glutamine metabolism and protein balance.

PMID- 11844643
TI  - Relation between glutamine, branched-chain amino acids, and protein metabolism.
AB  - The branched-chain amino acids (BCAAs; valine, isoleucine, and leucine) are the
      major nitrogen source for glutamine and alanine synthesis in muscle. Synthesis of
      glutamine, alanine, and BCAA use is activated in critical illnesses such as in
      sepsis, cancer, and trauma. The use of glutamine often exceeds its synthesis,
      resulting in the lack of glutamine in plasma and tissues. In critical illness,
      resynthesis of BCAA from branched-chain keto acids is activated, particularly in
      hepatic tissue. The BCAA released to circulation may be used for protein
      synthesis or synthesis of alanine and glutamine. Glutamine and/or alanine
      infusion has an inhibitory effect on the breakdown of body proteins and decreases
      BCAA catabolism in postabsorptive control, endotoxemic, and irradiated rats.
      Decreased protein breakdown also was observed when glutamine synthesis was
      activated by ammonia infusion. In conclusion some favorable effects of BCAA
      supply can be explained by its role in the synthesis of glutamine and some
      positive effects of glutamine exogenous supply can be explained by its effect on
      metabolism of BCAA.

PMID- 11844644
TI  - Clinical and metabolic effects of two lipid emulsions on the parenteral nutrition
      of septic patients.
AB  - OBJECTIVE: We compared the metabolic and clinical effects of two lipid emulsions,
      long-chain triacylglycerols (LCT) and a mixture of medium- and long-chain
      triacylglycerols (MCT/LCT), in septic patients. METHODS: Both groups received
      total parenteral nutrition (TPN) with a solution enriched with branched-chain
      amino acids (BCAA). Seventy-two septic patients received TPN with MCT/LCT (group
      1) or LCT (group 2). Before starting TPN (basal) and 10 d after (final), various
      parameters were evaluated. RESULTS: Twenty-six subjects in each group completed
      the study. Both groups showed an increase in cholestasis enzymes, with no
      significant changes in lipid parameters. The rise of retinol-binding protein and
      the recovery of nitrogen balance were significantly greater in group 1. A
      multivariate analysis of nutritional markers and catabolic parameters showed a
      better evolution in group 1 (P = 0.002). The MCT/LCT group exhibited a
      significant increase of insulin levels. Overall mortality and length of stay in
      the intensive care unit were not affected by the lipid emulsion. CONCLUSIONS: In
      septic patients who received TPN with a solution enriched with BCAAs, the use of
      an emulsion containing MCT provided them with a greater recovery of their
      nutrition status than the traditional LCT formula, without influencing the
      outcome.

PMID- 11844645
TI  - Predictors of weight gain and cardiovascular risk in a cohort of racially diverse
      kidney transplant recipients.
AB  - OBJECTIVE: Renal transplantation is associated with an increased risk of
      atherosclerotic cardiovascular disease and marked racial and ethnic disparities
      in graft and patient survival. We characterized differences in racial and ethnic
      susceptibility to weight gain, diabetes, and alterations in circulating lipid
      levels and isolated independent predictors of those changes in a diverse
      population of kidney transplant recipients. METHODS: The data for this analysis
      were drawn from a prospectively collected database of 506 renal transplant
      recipients obtained between 1983 and 1998. Univariate and multivariate analyses
      characterized differences in outcomes and predictors of cardiovascular risk by
      race and ethnicity. RESULTS: In all recipients, coronary artery disease was the
      most common cause of death, and African-American recipients had the shortest
      graft survival and the highest percentage of deaths. At 1 y post-transplantation,
      39% of African-American recipients were obese (body mass index > 30), and the
      odds ratios for post-transplant diabetes were 3.5 and 5 times greater in non
      white and obese recipients, respectively. CONCLUSIONS: Multiple regression
      analysis confirmed the predominant independent effect of African American race or
      ethnicity on weight gain; however, hypercholesterolemia was independent of race
      or ethnicity and predicted by cyclosporine treatment and post-transplant
      diabetes. Therefore, kidney transplantation represents a state of accelerated
      atherogenic risk induced in part by the metabolic effects of immunosuppressive
      medications and compounded by marked racial and ethnic disparities in weight gain
      and diabetes risk.

PMID- 11844646
TI  - Enforced mobilization, early oral feeding, and balanced analgesia improve
      convalescence after colorectal surgery.
AB  - OBJECTIVE: A postoperative regimen using a multimodal approach with enforced
      mobilization and early oral nutrition has been reported to improve convalescence
      but has not been compared with other postoperative regimens. METHODS: Forty
      patients undergoing elective colorectal surgery were randomly allocated to an
      intervention group receiving comprehensive information on the importance of
      mobilization, balanced anesthesia, and postoperative analgesia including epidural
      local anesthetics and enforced postoperative mobilization or a control group
      receiving anesthesia without epidural local anesthetics, postoperative analgesia
      with epidural morphine, and mobilization without fixed goals. All patients were
      offered early oral nutrition. The regimens were compared by means of ambulation
      time and physical activity, voluntary muscle strength, pulmonary function, and
      body composition. RESULTS: The ambulation time improved substantially within 22 h
      in the intervention group versus 3 h in the control group on day 1 (P = 0.0004)
      and within 8 h versus 2 h on day 4 (P = 0.0003). The voluntary strength of the
      quadriceps muscle decreased by 3% in the intervention group versus 15% in the
      control group on day 7 (P = 0.04). Two months postoperatively, the difference
      between groups was the same (P = 0.02). CONCLUSION: This active per- and
      postoperative regimen based on a multimodal approach improved ambulation time and
      muscle function during admission and late convalescence.

PMID- 11844647
TI  - Impedance vector distribution by sex, race, body mass index, and age in the
      United States: standard reference intervals as bivariate Z scores.
AB  - Bioelectrical impedance measurements were collected in the Third National Health
      and Nutrition Examination Survey (NHANES III), but their results have not been
      published. In the NHANES III population, resistance (R) and reactance (Xc) values
      at 50-kHz frequency were obtained with a Valhalla Scientific meter (model 1990B;
      San Diego, CA, USA). The RXc graph method was used to identify bivariate pattern
      distributions of mean vectors (95% confidence ellipses by sex, race, age, and
      body mass index [BMI]), and individual impedance vectors (50%, 75%, and 95%
      tolerance ellipses). Data from 10 222 adults (5261 men and 4961 women) formed 90
      four-way classification groups, with two sexes, three races or ethnicities (non
      Hispanic white, non-Hispanic black, Mexican American), five age classes (20-29,
      30-39, 40-49, 50-59, and 60-69 y), and three BMI classes (19-24.9, 25-29.9, and
      30-34.9 kg/m(2)). Sex, race or ethnicity, BMI and age, in decreasing order,
      influenced the vector distribution pattern. Mean vectors in women were
      significantly longer than those in men. Within each sex, the mean vector of non
      Hispanic white subjects was shorter and with a smaller phase angle than that of
      corresponding BMIs from the two other race/ethnic populations. Tolerance ellipses
      were calculated from sex- and race-specific reference populations 20 to 69 y old
      and 19 < or = BMI < 30 kg/m(2) (8022 subjects, 4226 men and 3796 women). After
      transformation of impedance vector components into bivariate Z scores
      (standardized deviates, as differences from the mean divided by the standard
      deviation of the reference population), we constructed one standard, reference,
      RXc-score graph (50%, 75%, and 95% tolerance ellipses) that can be used with any
      analyzer in any population. The pattern of impedance vector distribution and
      reference bivariate intervals for the individual impedance vector are presented
      for comparative studies (free software at E-mail: apiccoli@unipd.it).

PMID- 11844648
TI  - Provision of phosphorylatable substrate during hypoxia decreases jejunal barrier
      function.
AB  - OBJECTIVES: There is an emerging consensus that early enteral nutrition benefits
      the high-risk surgical patient. However, in patients with inadequate
      gastrointestinal perfusion, food in the intestine may increase the oxygen demand
      beyond that which can be satisfied by the available delivery, potentially leading
      to intestinal malfunction. The effect of metabolic substrate on gastrointestinal
      function during various oxygenation states was investigated. METHODS: Jejunal
      samples obtained from 32 male Sprague-Dawley rats (263 +/- Q15 g) were stripped
      of the muscularis, mounted in modified Ussing chambers, and randomized to be
      incubated in media equilibrated with one of four gas mixtures (95%, 75%, 50%, and
      25% oxygen). After equilibration, fluorescent probes (4400 and 17 200 molecular
      weight [MW]) were added to the incubation media on the mucosal side. The rate of
      probe accumulation on the serosal side was determined before and after the
      addition of one of four substrates to the mucosal medium: mannitol (an osmotic
      control), glucose (which is transported, phosphorylated, and metabolized), 2
      deoxyglucose (a glucose analog that is transported and phosphorylated but not
      metabolized), or 3-O-methylglucose (a glucose analog that is transported but not
      phosphorylated or metabolized). RESULTS: Lumenal glucose, 2-deoxyglucose, and 3-O
      methylglucose increased permeation of the 4400-MW probe at all oxygen levels,
      whereas mannitol did not alter permeation in the 95% and 75% oxygen groups.
      Lumenal glucose increased (P < 0.05) the permeation rate of the 17 200-MW probe
      at all oxygen levels, whereas 2-deoxyglucose and 3-O-methylglucose did not
      increase the permeation rate of the 17 200-MW probe until oxygen was lowered to
      75% and 50%, respectively. Regardless of substrate treatment, jejunal permeation
      of the 4400-MW (P < 0.001) and 17 200-MW (P < 0.05) probes increased in the 25%
      and 50% oxygen groups compared with the 75% and 95% oxygen groups. CONCLUSIONS:
      These initial results suggest that the provision of lumenal nutrients exacerbates
      the loss of gastrointestinal barrier function during hypoxia. Although the early
      provision of nutrients is an important intervention in acutely injured patients,
      care must be taken to ensure that gastrointestinal perfusion is adequate to allow
      substrate metabolism and prevent further compromise in gastrointestinal function.

PMID- 11844649
TI  - The French paradox: possible involvement of ethanol in the protective effect
      against cardiovascular diseases.
AB  - OBJECTIVES: This review surveyed the literature on the cardioprotective effects
      of moderate alcohol consumption. METHODS: The putative cardioprotective effects
      of alcohol and other substances in alcoholic beverages are discussed by taking
      "the French paradox" as a starting point. A survey of the literature highlighted
      various hypotheses explaining the protective effects of moderate alcohol
      consumption. RESULTS: The positive effects of moderate quantities of alcohol have
      been attributed in part to increased plasma levels of high-density lipoprotein,
      an inhibition of platelet aggregation, and improved endothelial function. Many
      investigators have claimed that wine is the significant factor explaining the
      French paradox. Red wine has been shown ex vivo to inhibit low-density
      lipoprotein oxidation, increase antioxidant capacity in humans, and reduce
      susceptibility of human plasma to lipid peroxidation. The non-alcoholic fraction
      of wine, represented mainly by phenolic compounds, may be the primary factor
      responsible for this protective effect. However, the protective effects are not
      restricted to a particular type of alcoholic drink, suggesting that alcohol per
      se rather than compounds specific to certain beverages reduces mortality risk.
      CONCLUSIONS: It is difficult to explain the effect of alcohol on risk factors
      associated with cardiovascular diseases by a uniform biochemical mechanism.
      Moreover, its protective effects are counterbalanced by its addictive properties.

PMID- 11844650
TI  - Estrogen, statins, and polyunsaturated fatty acids: similarities in their actions
      and benefits-is there a common link?
AB  - OBJECTIVES: To investigate whether there is any common link between estrogen,
      statins, and polyunsaturated fatty acids (PUFAs), which have similar actions and
      benefits. METHODS: To critically review the literature pertaining to the actions
      of estrogen, statins, and various PUFAs. RESULTS: Estrogen, statins, and PUFAs
      enhance nitric oxide synthesis, suppress the production of proinflammatory
      cytokines such as tumor necrosis factor(alpha), interleukin-1, interleukin-2, and
      interleukin-6, show antioxidant-like and antiatherosclerotic properties, have
      neuroprotective actions, and by themselves or their products inhibit tumor cell
      proliferation and improve osteoporosis. Estrogen, statins, and PUFAs not only
      have similar actions but also appear to interact with each other. For instance,
      the binding of estrogen to its receptor on the cell membrane may be determined by
      its lipid content, statins and PUFAs inhibit 3-hydroxy-3-methylglutaryl coenzyme
      A reductase activity, statins influence the metabolism of PUFAs, and PUFA
      deficiency enhances 3-hydroxy-3-methylglutaryl coenzyme A reductase activity.
      Statins and PUFAs inhibit tumor cell proliferation, suppress ras activity, and
      may prevent neurodegeneration and improve cognitive functions such as learning
      and memory. This suggests that PUFAs might be mediators of the actions of
      statins. Estrogen boosts cognitive performance in women after menopause and may
      protect against Alzheimer's disease. CONCLUSIONS: The common link between
      estrogen, statins, and PUFAs may be nitric oxide. Hence, a combination(s) of
      estrogen or its derivatives, statins, and various PUFAs may form a novel approach
      in the management of various conditions such as hyperlipidemias, coronary heart
      disease, atherosclerosis, osteoporosis, cancer, neurodegenerative conditions, and
      to improve memory.

PMID- 11844651
TI  - Effects of caffeine, vitamin D, and other nutrients on quantitative phalangeal
      bone ultrasound in postmenopausal women.
AB  - OBJECTIVE: We investigated the controversial effects of coffee and other
      nutrients on bone mass. METHODS: In a study of 93 healthy postmenopausal women
      (mean +/- standard deviation: 57.3 +/- 7.1 y old and 8.9 +/- 7.5 y since
      menopause) selected on the basis of not having changed their eating habits since
      premenopause, not smoking, not exercising, not receiving hormone-replacement
      therapy, and having a weight in the range of 70% to 130% of their ideal weights,
      amplitude-dependent speed of sound (Ad-SOS) was determined by quantitative bone
      ultrasound, and a prospective 7-d diet survey evaluated the intake of caffeine
      and nutrients involved in calcium metabolism. Women were stratified according to
      their caffeine, calcium, and vitamin D intakes and ratios of calcium to
      phosphorus and to protein. Ad-SOS differed only with vitamin D intake and was
      greater in the group taking at leasst 400 IU/d (P < 0.0001). RESULTS: In simple
      and multiple regression analyses, the only significant variable that affected Ad
      SOS and nutrient intake was vitamin D (P < 0.0001). Phalangeal bone Ad-SOS was
      influenced only by the intake of vitamin D, not of caffeine or other nutrients.
      CONCLUSIONS: This lack of effect of caffeine and protein may be related to good
      nutritional intake or the low levels of caffeine consumed.

PMID- 11844652
TI  - Racial disparities in weight gain after renal transplantation.

PMID- 11844653
TI  - Optimization of surgical care.

PMID- 11844654
TI  - Enteral or parenteral nutrition for the treatment of postoperatory
      gastrointestinal fistulae: a decision-making process.

PMID- 11844655
TI  - The albumin-nutrition connection: separating myth from fact.

PMID- 11844656
TI  - A pilot study of the safety and efficacy of cholestin in treating HIV-related
      dyslipidemia.
AB  - OBJECTIVE: We collected preliminary safety and efficacy data on the effects of
      Cholestin, a statin-containing dietary supplement, in individuals with
      dsylipidemia related to human immunodeficiency virus. METHODS: Fourteen adults
      with dsylipidemia related to human immunodeficiency virus characterized by
      hypercholesterolemia, hypertriacylglycerolemia, or both participated in a
      randomized, double-blind, placebo-controlled pilot study in an infectious disease
      clinic based in an academic medical center. Participants were randomly assigned
      to receive 1.2 g of Cholestin twice daily (n = 7) or placebo (n = 7) for 8 wk.
      The main outcome measures were safety (hepatic function tests, plasma human
      immunodeficiency virus-1 RNA levels, CD4(+) cell counts, adverse effects) and
      efficacy (fasting serum cholesterol: total, high- and low-density lipoproteins,
      and fasting serum triacylglycerols). Safety and efficacy outcomes were evaluated
      at 2- and 8-wk intervals. RESULTS: Twelve participants (n = 6 per group)
      completed the 8-wk treatment protocol. After 8 wk of treatment with Cholestin,
      there were significant declines from baseline in mean (+/- standard error of the
      mean) fasting total cholesterol (-30.8 +/- 8.8 versus 7.7 +/- 5.6; P = 0.01) and
      low-density lipoprotein cholesterol (-32.2 +/- 7.2 versus 26.3 +/- 14.2; P =
      0.01) versus placebo. Moreover, the decline in fasting total cholesterol was
      significant (-40.2 +/- 4.8 versus 2.8 +/- 11.9; P = 0.006) after 2 wk of therapy,
      at which time the low-density lipoprotein cholesterol approached significance (
      30.2 +/- 7.4 versus 4.4 +/- 15.2; P = 0.068). High-density lipoprotein
      cholesterol and triacylglycerol levels did not change at either time point. No
      adverse effects were seen with Cholestin. CONCLUSIONS: Cholestin may safely lower
      total and low-density lipoprotein cholesterol in patients with dsylipidemia
      related to human immunodeficiency virus. Larger and longer-term trials of this
      approach are warranted.

PMID- 11844657
TI  - Overview of presentations at the international association for dental research:
      Chiba, Japan, June 2001.

PMID- 11844658
TI  - Perioperative nutrition support.

PMID- 11844661
TI  - Affinity-driven selection of tripeptide inhibitors of ribonucleotide reductase.
AB  - Tripeptide libraries of the type Fmoc(W/F)XF were screened for binding to the
      large subunit of mouse ribonucleotide reductase (mRR), using a new, affinity
      chromatography method. A high-affinity tripeptide, FmocWFF, was found that
      inhibited mRR activity with a K(i) equal to that of AcFTLDADF, the heptapeptide
      corresponding to the C-terminus of the small subunit of mRR.

PMID- 11844662
TI  - Biphenylsulfonamide endothelin receptor antagonists. Part 3: structure-activity
      relationship of 4'-heterocyclic biphenylsulfonamides.
AB  - A number of 4'-heterocyclic biphenylsulfonamide derivatives, formally derived
      from BMS-193884 (1) by replacing the oxazole ring with other heterocyclic rings,
      are potent and selective endothelin A (ET(A)) receptor antagonists. Among the
      analogues examined, the pyrimidine derivative 18 is the most potent (K(i)=0.9 nM)
      and selective for the ET(A) receptor, approximately equivalent to 1.

PMID- 11844663
TI  - Amide derivatives of meclofenamic acid as selective cyclooxygenase-2 inhibitors.
AB  - This paper describes SAR studies involved in the transformation of the NSAID
      meclofenamic acid into potent and selective cyclooxygenase-2 (COX-2) inhibitors
      via neutralization of the carboxylate moiety in this nonselective COX inhibitor.

PMID- 11844664
TI  - Differential inhibition of polymerase and strand-transfer activities of HIV-1
      reverse transcriptase.
AB  - A new class of inhibitors of HIV-1 reverse transcriptase obtained by the
      systematic structural simplification of epicatechin and epigallocatechin gallates
      are also shown here to inhibit DNA-strand-transfer, a process critical to the
      completion of the HIV-1-RT reproduction and to recombination-associated mutation
      of the virus. Up to 80-fold selectivity for DNA-strand-transfer inhibition over
      polymerase inhibition was observed for a defined subset of these agents. Such
      specific DNA-strand-transfer inhibitors may have important therapeutic potential.

PMID- 11844665
TI  - A combinatorial library of indinavir analogues and its in vitro and in vivo
      studies.
AB  - A combinatorial library of 300HIV protease inhibitors has been synthesized. The
      library was screened against recombinant wild-type and mutant HIV-1 protease
      enzymes. The pharmacokinetics of the library was evaluated by dosing in dogs.
      Compounds that are notably more potent than indinavir and have favorable
      pharmacokinetic properties were identified.

PMID- 11844666
TI  - Structure-based design of cyclooxygenase-2 selectivity into ketoprofen.
AB  - We have recently described how to achieve COX-2 selectivity from the non
      selective inhibitor indomethacin (1) using a combination of a pharmacophore and
      computer 3-D models based on the known X-ray crystal structures of
      cyclooxygenases. In the present study we have focused on the design of COX-2
      selective analogues of the NSAID ketoprofen (2). The design is similarly based on
      the combined use of the previous pharmacophore together with traditional
      medicinal chemistry techniques motivated by the comparative modeling of the 3-D
      structures of 2 docked into the COX active sites. The analysis includes use of
      the program GRID to detect isoenzyme differences near the active site region and
      is aimed at suggesting modifications of the basic benzophenone frame of the lead
      compound 2. The resulting series of compounds bearing this central framework is
      exemplified by the potent and selective COX-2 inhibitor 17 (LM-1669).

PMID- 11844667
TI  - New anti-malarial compounds from database searching.
AB  - In a serendipitous result, pharmacophores generated for the database searching
      for new non-nucleoside inhibitors of the HIV-1 reverse transcriptase enzyme
      unearthed 12 new lead compounds which were active against the Plasmodium
      falciparum strain of malaria.

PMID- 11844669
TI  - Solid-phase synthesis of c(RGDfK) derivatives: on-resin cyclisation and lysine
      functionalisation.
AB  - The cyclic pentapeptide c(RGDfK), a selective ligand for the alpha(v)beta3
      integrin, was synthesised on solid phase. All synthetic operations including the
      cyclisation step and the appendage of the Bolton-Hunter reagent was conducted on
      resin.

PMID- 11844668
TI  - Structure-activity relationships of novel anti-malarial agents. Part 3: N-(4
      acylamino-3-benzoylphenyl)-4-propoxycinnamic acid amides.
AB  - We have described 5-(4-propoxycinnamoylamino)-2-(4-tolylacetylamino)benzophenone
      6e as a novel lead for anti-malarial agents. Anti-malarial activity of these 5-(4
      propoxycinnamoylamino)benzophenones proved to be quite sensitive against
      variations of the acyl substituent at the 2-amino group. Best activity was
      obtained with phenylacetic acid moieties carrying small substituents in the para
      position. From the para-substituents evaluated, the trifluoromethyl group yielded
      the most active compound (6j) in this series (IC50=120 nM). Deviations from the
      phenylacetic acid substructure, shifting the substituent into the ortho-position
      or bulkier para-substituents resulted in a significant reduction in anti-malarial
      activity.

PMID- 11844670
TI  - Design and synthesis of peptide-based carboxylic acid-containing transition-state
      inhibitors of human neutrophil elastase.
AB  - In our search for a new agent, human neutrophil elastase (HNE) inhibitor, for the
      treatment of acute respiratory failure, we rationally designed and synthesized a
      series of peptide-based carboxylic acid-containing transition-state inhibitors.
      The presence of valyl moiety is found to be essential for potent in vitro
      inhibitory activity and also prevention of an undesirable toxicity. Of these,
      compound 9m has the most potent in vivo effect on HNE-induced lung hemorrhage in
      hamsters.

PMID- 11844671
TI  - Synthesis, hydrolytic activation and cytotoxicity of etoposide prodrugs.
AB  - Two 4'-propylcarbonoxy derivatives (2,3) of etoposide (1), a topoisomerase II
      inhibitor, were synthesized and evaluated as potential prodrugs for anticancer
      therapy. Their activation via hydrolysis mechanisms was determined as a function
      of pH in buffer solutions, in human serum and in the presence of carboxyl ester
      hydrolase. Cytotoxicity was determined on various tumor cell lines and compared
      to the parent compound. On cell lines exhibiting resistance to etoposide we
      observed an enhanced cytotoxicity of the prodrugs of up to three orders of
      magnitude.

PMID- 11844672
TI  - Total synthesis and semi-synthetic approaches to analogues of antibacterial
      natural product althiomycin.
AB  - Numerous analogues of the naturally occurring antibiotic althiomycin have been
      synthesised exploiting both total- and semi-synthetic methodologies. The
      antibacterial activity of these derivatives has been determined in whole cell
      assays and indicates the natural product exhibits a restricted SAR.

PMID- 11844673
TI  - Cytotoxic and antibacterial activity of 2-oxopurine derivatives.
AB  - Initial screening of the cytotoxic and antibacterial properties of 6-substituted
      2-oxopurines and dihydro-2-oxopurines revealed that several compounds exhibited
      cytotoxicity against K-562 cells in the same range as the well known antileukemic
      drug 6-mercaptopurine. Most compounds were also tested for inhibitory effect on a
      Gram-positive bacterium, Lactobacillus casei, as well as the mycobacterium
      Mycobacterium tuberculosis. Generally the 2-oxopurines exhibited low
      antibacterial effect.

PMID- 11844674
TI  - Studies on quinazolinones as dual inhibitors of Pgp and MRP1 in multidrug
      resistance.
AB  - The syntheses and SAR studies of various quinazolinone compounds are described
      for the dual inhibition of Pgp and MRP1 in multidrug resistance.

PMID- 11844675
TI  - 2-(anilinomethyl)imidazolines as alpha1A adrenergic receptor agonists: 2'
      heteroaryl and 2'-oxime ether series.
AB  - A series of 2'-heteroaryl and 2'-oxime anilinomethylimidazolines was prepared and
      evaluated in in vitro functional assays for cloned human alpha1A, alpha1B, and
      alpha1D receptor subtypes. Potent and selective alpha1A agonists have been
      identified in these series.

PMID- 11844676
TI  - Encounter with unexpected collagenase-1 selective inhibitor: switchover of
      inhibitor binding pocket induced by fluorine atom.
AB  - Phosphonamide-based inhibitors having trifluoromethyl moiety showed highly
      selective inhibition against MMP-1. A possible mechanism of the selectivity of
      MMP-1 inhibitors through the switchover of the binding pocket was speculated by
      computational calculations. As a consequence of the unexpected selectivity, the
      specific interaction of CF3 group of the inhibitor and Arg214 in the S1' pocket
      of MMP-1 conducted a low binding energy.

PMID- 11844677
TI  - Synthesis and antithrombotic activity of carbolinecarboxyl RGD sequence.
AB  - 3S-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid, RGDS, RGDV, RGDF and
      their linkers were synthesized. The anti-aggregation and adhesion of platelet
      indicated that the in vitro activities of the linkers remained at the same level
      as RGDS, RGDV, and RGDF (p>0.05). The antithrombotic activities in vivo
      suggested, however, that the potencies of RGDS, RGDV and RGDF were enhanced by
      the introduction of 3S-1,2,3,4-tetrahydro-beta-carboline-3-carboxyl group into
      their alpha amino group (p<0.05, 0.01 or 0.001).

PMID- 11844678
TI  - Synthesis and anti-angiogenic activity of 6-(1,2,4-thiadiazol-5-yl)-3-amino
      pyridazine derivatives.
AB  - General screening for inhibitors of microvessel growth in vitro in the rat aortic
      ring assay led to the discovery of a novel series of thiadiazole pyridazine
      compounds with potential anti-angiogenic activity. Chemical optimization produced
      orally active compounds with potent in vitro and in vivo anti-angiogenesis and
      anti-tumor activities.

PMID- 11844679
TI  - Alpha-L-RNA (alpha-L-ribo configured RNA): synthesis and RNA-selective
      hybridization of alpha-L-RNA/alpha-L-LNA chimera.
AB  - Synthesis of the novel alpha-L-ribofuranosyl phosphoramidite derivative was
      accomplished via the alpha-L-ribofuranosyl thymine nucleoside. Amidite was used
      in automated syntheses of chimeric oligonucleotides composed of mixtures of the
      novel alpha-L-RNA nucleotide monomer ((alphaL)T, alpha-L-ribo configured RNA),
      and DNA, LNA (T(L), locked nucleic acid) or alpha-L-LNA ((alphaL)T(L), alpha-L
      ribo configured locked nucleic acid) nucleotide monomers. For alpha-L-RNA/DNA and
      alpha-L-RNA/alpha-L-LNA chimeras, RNA-selective hybridization was obtained, for
      alpha-L-RNA/alpha-L-LNA chimera we found increased binding affinity compared to
      the corresponding DNA:RNA reference duplex. In addition, alpha-L-RNA/alpha-L-LNA
      chimera displayed significant stabilization towards 3'-exonucleolytic
      degradation. These results indicate that alpha-L-RNA/alpha-L-LNA chimeras deserve
      further evaluation as antisense molecules.

PMID- 11844680
TI  - Enzymatic synthesis of monocyclic beta-lactams.
AB  - An Mg2+ and ATP dependent beta-lactam synthetase (BLS) catalyses formation of a
      beta-lactam ring during the biosynthesis of clavulanic acid, an important beta
      lactamase inhibitor. An epimeric mixture of a 2-methylated derivative of the
      natural BLS substrate N2-(2-carboxyethyl)-L-arginine was synthesised and found to
      be a substrate for the enzyme. The epimeric products were characterised by 1H NMR
      and mass spectrometric analyses. The results suggest that a modified version of
      BLS might be used to catalyse the preparation of intermediates useful for the
      synthesis of beta-lactam antibiotics.

PMID- 11844681
TI  - Synthesis of 5,6-dihydro-11H-benzo[5,6]-cyclohepta[1,2-b]pyridin-11-ylidene)-1
      piperidine-N-cyanoguanidine derivatives as inhibitors of ras farnesyl protein
      transferase.
AB  - A series of novel N-cyanoguanidine tricyclic farnesyl protein transferase (FPT)
      inhibitors was prepared. Replacement of a piperidine amide-group with a N
      cyanoguanidine functionality increased FPT activity. X-ray crystal structure
      determination of 42 complexed with FPT revealed differences in the interactions
      of the amide and N-cyanoguanidine groups with the protein.

PMID- 11844682
TI  - Design and synthesis of novel benzofurans as a new class of antifungal agents
      targeting fungal N-myristoyltransferase. Part 2.
AB  - Modification of the C-2 position of a benzofuran derivative 6 (RO-09-4609), an N
      myristoyltransferase (Nmt) inhibitor, has led us to discover antifungal agents
      that are active in a murine systemic candidiasis model. The drug design is based
      on the analysis of a crystal structure of a Candida Nmt complex with 2. The
      optimization has been guided by various biological evaluations including a quasi
      in vivo assay and pharmacokinetic analysis.

PMID- 11844684
TI  - Absorption studies on aminoglycoside binding to the packaging region of human
      immunodeficiency virus type-1.
AB  - The binding of paromomycin, neomycin B, and three analogues of neomycin to a 176
      mer RNA from the packaging region of HIV-1 (LAI) has been studied using UV
      absorption spectroscopy at wavelengths between 200 and 300 nm. From plots of
      absorption as a function of drug concentration, values of binding constants for
      these drugs on RNA were determined.

PMID- 11844683
TI  - The discovery of acylated beta-amino acids as potent and orally bioavailable VLA
      4 antagonists.
AB  - Acylated beta-amino acids are described as potent, specific and orally
      bioavailable antagonists of VLA-4. The initial lead was identified from a
      combinatorial library. Subsequent optimization using a traditional medicinal
      chemistry approach led to significant improvement in potency (up to 8-fold) while
      maintaining good pharmacokinetic properties.

PMID- 11844685
TI  - A novel series of hybrid compounds derived by combining 2-aminotetralin and
      piperazine fragments: binding activity at D2 and D3 receptors.
AB  - A series of 7-hydroxy-2-[N-alkyl-(N-(4-phenylpiperazine)-alkyl)amino]tetralins
      was developed based on a novel hybrid approach that combined 2-aminotetralin and
      arylpiperazine pharmacophoric moieties. Our preliminary study revealed that a
      four-methylene butyl linker produced very potent compounds for both the D2 and D3
      receptors. Further structure-activity studies led to a novel template showing 50-
      to 100-fold selectivity for the D3 receptor.

PMID- 11844686
TI  - Synthesis of a magnosalin derivative, 4-(3,4,5-trimethoxyphenyl)-6-(2,4,5
      trimethoxyphenyl)-2-diethylaminopyrimidine, and the anti-angiogenic and anti
      rheumatic effect on mice by oral administration.
AB  - We describe here the synthesis and the anti-angiogenic and anti-rheumatic
      activities of 4-(3,4,5-trimethoxyphenyl)-6-(2,4,5-trimethoxyphenyl)-2
      diethylaminopyrimidine (TAS-202), a derivative of magnosalin, which is a natural
      product isolated from Flos magnoliae. TAS-202 inhibited the proliferation of
      vascular endothelial cells more potently than magnosalin, and when given orally
      it inhibited basic fibroblast growth factor (bFGF)-induced angiogenesis and
      collagen-induced arthritis in mice. This magnosalin derivative with anti
      angiogenic effects is a candidate for the treatment of rheumatoid arthritis.

PMID- 11844687
TI  - A new class of type I protein geranylgeranyltransferase (GGTase I) inhibitor.
AB  - Replacement of the thiol groups in 1, a potent and highly selective Candida
      albicans GGTase I inhibitor discovered through screening, with an imidazole ring
      was achieved by using solid phase synthesis. A non-thiol compound, 7, was found
      as a representative of a new class of potent C. albicans GGTase I inhibitor with
      high selectivity against human GGTase I.

PMID- 11844688
TI  - Di- and trisubstituted pyrazolo[1,5-a]pyridine derivatives: synthesis, dopamine
      receptor binding and ligand efficacy.
AB  - Based on the lead molecule FAUC 113, a series of di- and trisubstituted
      pyrazolo[1,5-a]pyridine derivatives was synthesized and investigated for their
      dopamine receptor binding profile. The carbonitrile 11a (FAUC 327) showed
      excellent pharmacological properties combining high D4 affinity (K(i)=1.5 nM) and
      selectivity with significant intrinsic activity (31%) in low nanomolar
      concentrations (EC50=1.5 nM).

PMID- 11844689
TI  - Substituted N-(3,5-dichlorobenzenesulfonyl)-L-prolyl-phenylalanine analogues as
      potent VLA-4 antagonists.
AB  - A series of substituted N-(3,5-dichlorobenzenesulfonyl)-L-prolyl- and alpha
      methyl-L-prolyl-phenylalanine derivatives was prepared as VLA-4/VCAM antagonists.
      The compounds showed excellent potency with a wide variety of neutral, polar,
      electron withdrawing or donating groups on the phenylalanine ring (IC50
      approximately 1 nM). Heteroaryl ring substitution for phenylalanine was also well
      tolerated. Pharmacokinetic studies in rat were performed on a representative set
      of compounds in both series.

PMID- 11844690
TI  - Solution and solid-phase synthesis of potent inhibitors of hepatitis C virus NS3
      proteinase.
AB  - A versatile route for the synthesis of homochiral alpha-ketoamide analogues of
      amino acids is described. Incorporation of this functionality into peptide
      sequences using either solution or solid-phase chemistry resulted in potent
      inhibitors of the Hepatitis C Virus NS3 proteinase.

PMID- 11844691
TI  - 4-amidinobenzylamine-based inhibitors of urokinase.
AB  - A series of 4-amidinobenzylamine-based peptidomimetic inhibitors of urokinase was
      synthesized. The most potent one, benzylsulfonyl-D-Ser-Ala-4-amidinobenzylamide
      16, inhibits uPA with a K(i) of 7.7 nM but is less selective than 10 with a Gly
      as P2 residue. Hydroxyamidine and carbonate prodrugs were prepared, which are
      rapidly converted into the active inhibitors in rats after subcutaneous
      application.

PMID- 11844692
TI  - Two neolignans from Perilla frutescens and their inhibition of nitric oxide
      synthase and tumor necrosis factor-alpha expression in murine macrophage cell
      line RAW 264.7.
AB  - Two neolignans were isolated from leaves of Perilla frutescens (Labiatae) as
      inhibitors of nitric oxide syntheses (IC50 5.9 microM and 53.5 microM,
      respectively) and tumor necrosis factor-alpha in lipopolysaccharide-activated RAW
      264.7 cells. Their structures were identified as 1beta,2alpha,3beta,4alpha-1,2
      dimethyl-3,4-bis-(2,4,5-trimethoxyphenyl)-cyclobutane (magnosalin), and
      1alpha,2beta,3beta,4alpha-1,2-dimethyl-3,4-bis-(2,4,5-trimethoxyphenyl)
      cyclobutane (andamanicin), and their activities were confirmed as resulted from
      the suppressed expression of inducible nitric oxide synthase enzyme and from the
      secretion of tumor necrosis factor-alpha from activated macrophages.

PMID- 11844693
TI  - Synthesis and biological evaluation of imidazol-2-one and 2-cyanoiminoimidazole
      derivatives: novel series of PDE4 inhibitors.
AB  - This communication describes the synthesis and in vitro PDE4 inhibitory activity
      of a novel series of imidazol-2-one and 2-cyanoiminoimidazole derivatives. The
      compounds described were also tested in in vivo models to evaluate their anti
      inflammatory activity after topical administration as well as their gastro
      intestinal side effects. Several compounds proved to be potent PDE4 inhibitors
      and some 2-cyanoiminoimidazoles showed less pronounced gastro-intestinal side
      effects than reference compounds but maintained anti-inflammatory activity after
      topical administration.

PMID- 11844694
TI  - Leishmanicidal activity of some aliphatic diamines and amino-alcohols.
AB  - A number of aliphatic diamines and amino-alcohols and several of their alkyl,
      acyl and carbamoyl derivatives, have been synthesised and evaluated in vitro on
      cultures of Leishmania spp. In general, diamine derivatives resulted to be more
      potent than their amino-alcohol or amino-ether analogues. Two diamine derivatives
      (8b and 9d) and one amino-alcohol (6a) showed a fair inhibition of parasite
      growth, at concentrations below 10 microg/mL, with potencies close to that of the
      reference drug, amphotericin B. Some SAR considerations have been deduced.

PMID- 11844696
TI  - Syntheses of novel antimycobacterial combinatorial libraries of structurally
      diverse substituted pyrimidines by three-component solid-phase reactions.
AB  - A new pyrimidine based scaffold has been developed by three-component solid-phase
      syntheses. The utility of scaffolds was demonstrated by synthesizing libraries of
      80 substituted pyrimidines (a-p), (a-p), 14(a-p), 15(a-p), 16(a-p). Among 80
      compounds screened, six compounds, 12i, 13c, 14d, 14e, 14o, and 15d showed in
      vitro activity against Mycobacterium tuberculosis (MABA) at a concentration of 50
      and 25 microg/mL

PMID- 11844695
TI  - Human glucagon receptor antagonists based on alkylidene hydrazides.
AB  - A series of alkylidene hydrazide derivatives containing an alkoxyaryl moiety was
      optimized. The resulting hydrazide-ethers were competitive antagonists at the
      human glucagon receptor. Pharmacokinetic experiments showed fast clearance of
      most of the compounds tested. A representative compound [4-hydroxy-3-cyanobenzoic
      acid (4-isopropylbenzyloxy-3,5-dimethoxymethylene)hydrazide] with an IC50 value
      of 20 nM was shown to reduce blood glucose levels in fasted rats.

PMID- 11844697
TI  - Beta-carboline-carbohydrate hybrids: molecular design, chemical synthesis and
      evaluation of novel DNA photocleavers.
AB  - Beta-carboline present in beta-carboline alkaloids from marine organisms was
      found, for the first time, to cleave DNA at the guanine site upon irradiation
      with UV light with a long wavelength without any additive, and beta-carboline
      carbohydrate hybrid system was effective for DNA cleavage.

PMID- 11844698
TI  - Induction of apoptosis in HL-60 cells by photochemically generated hydroxyl
      radicals.
AB  - Reactive oxygen species (ROS), especially hydroxyl radicals are postulated to
      mediate apoptosis of the cell. Here we demonstrate that hydroxyl radicals
      generated selectively by photolysis of a photo-Fenton reagent, N,N'-bis(2
      hydroperoxy-2-methoxyethyl)-1,4,5,8-naphthaldiimide (NP-III), induce apoptosis in
      HL-60 (human promyelocytic leukemia) cells involving the activation of caspase-3.

PMID- 11844699
TI  - CCR5 antagonists: bicyclic isoxazolidines as conformationally constrained N-1
      substituted pyrrolidines.
AB  - A series of CCR5 antagonists containing bicyclic isoxazolidines was generated
      through a nitrone mediated cycloaddition with olefins bearing the preferred
      pharmacophores previously described. Potent antagonists (3 and 16) were generated
      with enhanced affinity for the CCR5 receptor while maintaining antiviral activity
      against HIV.

PMID- 11844700
TI  - An additional 2'-ribofuranose residue at a specific position of the DNA primer
      prevents Its elongation by HIV-1 reverse transcriptase.
AB  - Oligodeoxynucleotides containing 2'-O-beta-D-ribofuranosyladenosine were prepared
      and used as modified primers in RNA-templated DNA synthesis catalyzed by HIV
      reverse transcriptase. It was shown that the additional 2'-ribofuranose residue
      in specific position of primer prevents its elongation.

PMID- 11844701
TI  - Identification of unique VLA-4 antagonists from a combinatorial library.
AB  - A combinatorial library of 28 pools of 180 compounds (345 diastereomers) was
      designed and prepared in support of the delineation of the SAR of two
      prototypical VLA-4 antagonists. Deconvolution of the active pools led to the
      identification of three novel series of VLA-4 antagonists with low nanomolar
      potencies.

PMID- 11844702
TI  - Pyridazine based inhibitors of p38 MAPK.
AB  - Trisubstituted pyridazines were synthesized and evaluated as in vitro inhibitors
      of p38MAPK. The most active isomers were those possessing an aryl group alpha and
      a heteroaryl group beta relative to the nitrogen atom in the 2-position of the
      central pyridazine. Additionally, substitution in the 6-position of the central
      pyridazine with a variety of dialkylamino substituents afforded a set of
      inhibitors having good (p38 IC50 1-20 nM) in vitro activity.

PMID- 11844703
TI  - Insertion of 2-carboxysuccinate and tricarballylic acid fragments into cyclic
      pseudopeptides: new antagonists for the human tachykinin NK-2 receptor.
AB  - A series of cyclic pseudopeptides were synthesized containing the sequence -Trp
      Phe-(D)-PhePsiCH2NH-, the terminal ends of which were bound to 2-carboxy
      succinate or enantiomerically enriched tricarballylic acid to give the final
      cyclic structures. These two molecules and their subsequent derivatives were
      screened for h-NK2 receptor binding and functional antagonist activity on the
      rabbit urinary bladder.

PMID- 11844704
TI  - Benzylidene rhodanines as novel inhibitors of UDP-N-acetylmuramate/L-alanine
      ligase.
AB  - Benzylidene rhodanines are novel inhibitors of UDP N-acetylmuramate/L-alanine
      ligase. They showed selective whole-cell activity against the Gram-positive MRSA
      but not against the Gram-negative Escherichia coli. Their cytotoxic effect on
      mammalian CHO cells was also evaluated.

PMID- 11844705
TI  - A designed P1 cysteine mimetic for covalent and non-covalent inhibitors of HCV
      NS3 protease.
AB  - The difluoromethyl group was designed by computational chemistry methods as a
      mimetic of the canonical P1 cysteine thiol for inhibitors of the hepatitis C
      virus NS3 protease. This modification led to the development of competitive, non
      covalent inhibitor 4 (K(i) 30 nM) and reversible covalent inhibitors (6, K(i) 0.5
      nM; and 8 K*(i) 10 pM).

PMID- 11844706
TI  - Evolution, synthesis and SAR of tripeptide alpha-ketoacid inhibitors of the
      hepatitis C virus NS3/NS4A serine protease.
AB  - N-terminal truncation of the hexapeptide ketoacid 1 gave rise to potent
      tripeptide inhibitors of the hepatitis C virus NS3 protease/NS4A cofactor
      complex. Optimization of these tripeptides led to ketoacid 30 with an IC50 of
      0.38 microM. The SAR of these tripeptides is discussed in the light of the
      recently published crystal structures of a ternary tripetide/NS3/NS4A complexes.

PMID- 11844707
TI  - New indene-derivatives with anti-proliferative properties.
AB  - Metabolites of the non-steroidal anti-inflammatory drug Sulindac inhibit cell
      proliferation by affecting several intracellular signaling pathways including the
      tumorigenic Ras/Raf/MAPK pathway. Here, we report the synthesis of eight new
      indene derivatives derived from the Sulindac structure, and present data on their
      anti-proliferative properties and their effects on the p21ras protein.

PMID- 11844708
TI  - Meiosis activating sterols derived from diosgenin.
AB  - Continuing research based on the meiosis activation properties of the endogenous
      sterol FF-MAS is reported. The synthesis and SAR of 16- and 26-substituted
      sterols are described, utilising diosgenin as starting material. Selected sterols
      were tested for their ability to induce oocyte maturation in hypoxanthine
      arrested mouse oocytes in vitro.

PMID- 11844709
TI  - Synthesis and cytotoxicity of 3,4-diaryl-2(5H)-furanones.
AB  - A series of 3,4-diaryl-2(5H)-furanone derivatives were synthesized and evaluated
      for their cytotoxicity in a small panel of cancer cell lines. Four out of 10
      compounds in this series, for example 3-(3,4,5-trimethoxyphenyl)-4-(4
      methoxyphenyl)-, 3-(3,4,5-trimethoxyphenyl)-4-(3-hydroxy-4-methoxyphenyl)-, 3
      (3,4,5-trimethoxyphenyl)-4-(3-amino-4-methoxyphenyl)-, and 3-(3,4,5
      trimethoxyphenyl)-4-(2-naphthyl)-2(5H)-furanones, were found to have potent
      cytotoxic activities with ED50 values of less than 20 nM in most of the cell
      lines tested.

PMID- 11844711
TI  - Update on the mechanisms of action of antiepileptic drugs.
AB  - After a hiatus of almost 20 years, nine new antiepileptic drugs were licensed
      during the last decade of the 20th century. Expansion of the range of drug
      treatments for epilepsy complicates selection of the most suitable drug, or
      combination of drugs, for individual patients. Clinical experience suggests that
      mechanism of action may become an important criterion in this decision-making
      process. At the cellular level, three major pharmacological actions are
      recognised: modulation of voltage-dependent ion channels, enhancement of
      inhibitory neurotransmission, and attenuation of excitatory transmission. This
      review provides an update on the principal mechanisms of action of a range of
      established and modern antiepileptic drugs.

PMID- 11844712
TI  - Semiology of typical and atypical Rolandic epilepsy: a video-EEG analysis.
AB  - Since the first descriptions of Rolandic Epilepsy or benign epilepsy with
      centrotemporal spikes (BECTS), typical and atypical forms have been reported.
      Indeed, classical focal seizures are sometimes associated with various atypical
      ictal symptoms and cognitive or behavioural disorders. In an effort to define
      early clinical and EEG criteria allowing early distinction between typical and
      atypical forms, we recently conducted a prospective study in a cohort of children
      with Rolandic Epilepsy. The results of this study have been reported elsewhere.
      We now discuss the semiological characteristics, and comment on the video-EEG
      data collected during this study. Symptoms were classified into three major
      categories: "classical focal seizures"; "spike and wave related symptoms"; and
      "paraictal symptoms". Classical focal seizures constitute the electroclinical
      expression of the development and the propagation of a focal cortical neuronal
      discharge. "Spike and wave related symptoms" are brief neurological or
      neuropsychological phenomena having a relatively strict temporal relation with
      individual components of isolated focal or generalized spikes and waves.
      "Paraictal symptoms" consist of acquired progressive and fluctuating motor or
      cognitive deficits and are not directly correlated with Todd paralysis. We
      present detailed video-EEG material of selected cases and discuss the usefulness
      of such distinctions in terminology. We suggest that variability in clinical
      expression probably reflects the implication of different pathophysiological
      mechanisms, which in turn could explain differences in sensitivity to treatment.
      (Published with videosequences.)

PMID- 11844713
TI  - Pathogenesis of Lennox-Gastaut syndrome: considerations and hypotheses.
AB  - No other epilepsy more substantially combines cryptogenicity and intractability
      than does Lennox-Gastaut Syndrome. Although antecedent neurological conditions
      have preceded LGS in some patients, others with similar ills fail to develop this
      syndrome, and precise charting of the pathway between any presumed aetiology and
      the epilepsy has eluded researchers. Despite these frustrations, LGS has elicited
      a host of publications over the years, possibly because it combines features of
      many other epileptic disorders and thereby occupies a crossroads position among
      them. Lacking a comprehensive experimental model of LGS, this article combines
      relevant data from several clinical and basic sources in order to formulate a
      concept of pathogenesis. Data are presented to suggest that the occurrence of
      factors enhancing excitability during a vulnerable period of cortical and
      thalamic development may permanently imprint a bilateral, diffuse epileptogenic
      system upon the mammalian brain.

PMID- 11844714
TI  - Outcome of corpus callosotomy and other pediatric epilepsy surgery: parental
      perceptions.
AB  - PURPOSE: Parental perceptions regarding the outcome of epilepsy surgery in their
      children were assessed preoperatively via telephone survey. METHODS: Twenty-seven
      parents - sixteen mothers (MO), eleven fathers (FA) - of sixteen children (nine
      boys, seven girls; ages 6 months-18 years) with intractable epilepsy (refractory
      to > or = 3 anticonvulsants) were interviewed. Twenty-four questions were posed
      during single, 20-minute sessions to both parents. RESULTS: A majority of parents
      (63% MO, 82% FA) would consider epilepsy surgery successful if it achieved > or =
      75% seizure reduction. Incomplete seizure control would even be acceptable if the
      overall number of seizures were reduced (69% MO, 18% FA). In order to gain
      seizure remissions, behavioral deterioration would be accepted (57% MO, 50% FA).
      Less than total seizure control would be accepted if surgery produced behavioral
      improvement (57% MO, 51% FA, Kappa > 0.6). For seizure reduction, parents would
      accept: visual field deficits (82% MO, 67% FA), short-term memory deficits (33%
      MO, 75% FA), and speech problems (56% MO, 17% FA). CONCLUSION: Parents of
      children with medically-resistant seizures perceive adverse physical and
      behavioral consequences of epilepsy surgery to be acceptable if there is adequate
      seizure control. Their acceptance of postoperative deficits underscores the
      magnitude of the handicap produced by chronic childhood epilepsy.

PMID- 11844715
TI  - Benign paroxysmal tonic upgaze of childhood with ataxia.
AB  - Paroxysmal tonic upgaze deviation (PTU) is a rare neuro-ophthalmological disorder
      with onset in infancy or early childhood. It consists of episodes of sustained,
      conjugate, upward deviation of the eyes, down beating saccades in attempted
      downgaze, apparently preserved horizontal eye movements, frequent association
      with mild ataxia or clumsiness at time of illness, normal metabolic,
      electroencephalographic and neuroradiological findings. Symptoms are frequently
      relieved by sleep and can be exacerbated by fatigue or illness. Although PTU
      generally tends to disappear spontaneously within a few months or years,
      subsequent case reports have demonstrated the heterogeneous nature of the
      syndrome with respect to outcome. To date, the pathogenesis of the condition is
      still unknown. We present a new case of PTU with ataxia occurring in an otherwise
      healthy child, as documented by video recording of the phenomenon.

PMID- 11844716
TI  - Cognitive function in adolescents and young adults in complete remission from
      benign childhood epilepsy with centro-temporal spikes.
AB  - Benign childhood epilepsy with centrotemporal spikes (BECTS) is a frequent,
      benign childhood epilepsy with a good prognosis. However, neuropsychological
      deficits have been reported during its active phase. In this study, we evaluate
      the long-term neuropsychological consequences of this reputedly benign epilepsy,
      particularly the relation between paroxysmal abnormalities and cerebral language
      lateralization. The neuropsychological outcomes concerning both overall cognitive
      and lateral hemispheric functions were studied in twenty-three adolescents and
      young adults in total recovery from BECTS, in thirty-three controls without any
      significant past neurological history and in ten adolescents and young adults
      with complete resolution of generalized idiopathic epilepsy (childhood absence
      epilepsy or CAE). Language lateralization was evaluated using classical
      neuropsychological procedures (dichotic listening tasks, dual-task procedure). No
      difference was seen in the three populations with respect to overall cognitive
      function: memory, language and the executive functions. Although the Performance
      IQ was lower in patients in remission from CAE, the results were within normal
      limits. However, qualitative analysis of the dual-task procedure suggested a
      different organizational pattern for cerebral language in adolescents and young
      adults in remission from BECTS as compared to controls and patients in remission
      from CAE. The different organization in cerebral pattern in BECTS patients
      appeared to be related to the initial epileptic focus as determined by the EEG
      and/or the sleep-recording. We discuss the relationship between the presence of
      paroxysmal anomalies in childhood and subtle functional lateralized hemispheric
      abnormalities in adulthood.

PMID- 11844717
TI  - Reversible aphasic disorder induced by lamotrigine in atypical benign childhood
      epilepsy.
AB  - PURPOSE: We studied an eleven year-old girl with atypical, benign partial
      epilepsy who acutely presented a severe aphasia associated with marked EEG
      deterioration after lamotrigine administration. A parallel monitoring of language
      disorders and EEG changes during the gradual withdrawal of lamotrigine was
      performed in order to evaluate their possible correlation with lamotrigine
      administration. METHODS: Detailed neuropsychological and linguistic examinations
      in association with awake and sleep EEG were periodically performed. RESULTS: The
      evolution of the aphasic disorder was closely related to the EEG abnormalities,
      and disappeared after the withdrawal of lamotrigine. CONCLUSIONS: We considered
      the hypothesis that our case could be an expression of a paradoxical reaction to
      lamotrigine, in which the transitory aphasic disorder was sustained by an
      epileptiform electric activation.

PMID- 11844720
TI  - Theory and testing in Landau-Kleffner Syndrome.

PMID- 11844723
TI  - Neuropsychology of musical perception: new perspectives.

PMID- 11844724
TI  - Optic ataxia as a result of the breakdown of the global tuning fields of parietal
      neurones.
AB  - Optic ataxia is characterized by an impaired visual control of the direction of
      arm reaching to a visual target, accompanied by defective hand orientation and
      grip formation. In humans, optic ataxia is associated with lesions of the
      superior parietal lobule (SPL), which also affect visually guided saccades and
      other forms of eye-hand coordination. In the last 10 years, anatomical and
      physiological studies of the SPL have shed new light on the role of parietal
      cortex in the control of combined eye-hand movements to visual targets, and on
      the underlying distributed network which links parietal to frontal cortex. A main
      emerging functional feature of SPL neurones seems to be their capacity to
      combine, in a spatially congruent fashion, different directional eye- and hand
      related information, that any coding scheme so far proposed, considers essential
      for the composition of motor commands for reaching. This integration occurs
      within the global tuning field of parietal neurones, is context-dependent and
      involves eye and hand information that shares the same directional properties.
      Depending on task demands, this integration of signals can result in the
      representation of different reference frames for coordinated eye-hand movements.
      The dynamic operations occurring within the global tuning fields might depend, at
      least in part, on the reciprocal sets of association connections linking the SPL
      and the premotor areas of the frontal lobe. From this picture, the SPL emerges as
      both a main source of visual input to the frontal cortex and a key structure for
      visuomotor integration based on re-entrant signalling and, therefore, as a
      crucial node in the visual control of movement. It is hypothesized that in
      parietal patients, the directional errors that characterize reaching are a
      consequence of the breakdown of the combination of directional eye and hand
      information within the global tuning fields of parietal neurones. In these
      patients, the spatial match among information about target location, eye and hand
      position, and movement direction would be prevented, so as to impair the
      composition of visually guided eye-hand movements. This breakdown could be
      dependent, at least in part, on the failure of a re-entrant frontoparietal
      signalling, an obvious consequence of the degeneration of the cortico-cortical
      systems linking parietal and frontal cortex. Cortico-cortical connections are, in
      fact, essential for shaping the dynamic properties of cortical neurones.

PMID- 11844725
TI  - Congenital amusia: a group study of adults afflicted with a music-specific
      disorder.
AB  - The condition of congenital amusia, commonly known as tone-deafness, has been
      described for more than a century, but has received little empirical attention.
      In the present study, a research effort has been made to document in detail the
      behavioural manifestations of congenital amusia. A group of 11 adults, fitting
      stringent criteria of musical disabilities, were examined in a series of tests
      originally designed to assess the presence and specificity of musical disorders
      in brain-damaged patients. The results show that congenital amusia is related to
      severe deficiencies in processing pitch variations. The deficit extends to
      impairments in music memory and recognition as well as in singing and the ability
      to tap in time to music. Interestingly, the disorder appears specific to the
      musical domain. Congenital amusical individuals process and recognize speech,
      including speech prosody, common environmental sounds and human voices, as well
      as control subjects. Thus, the present study convincingly demonstrates the
      existence of congenital amusia as a new class of learning disabilities that
      affect musical abilities.

PMID- 11844726
TI  - Calcium-activated potassium channel SK1- and IK1-like immunoreactivity in injured
      human sensory neurones and its regulation by neurotrophic factors.
AB  - Calcium-activated potassium ion channels SK and IK (small and intermediate
      conductance, respectively) may be important in the pathophysiology of pain
      following nerve injury, as SK channels are known to impose a period of reduced
      excitability after each action potential by afterhyperpolarization. We studied
      the presence and changes of human SK1 (hSK1)- and hIK1-like immunoreactivity in
      control and injured human dorsal root ganglia (DRG) and peripheral nerves and
      their regulation by key neurotrophic factors in cultured rat sensory neurones.
      Using specific antibodies, hSK-1 and hIK-1-like immunoreactivity was detected in
      a majority of large and small/medium-sized cell bodies of human DRG. hSK1
      immunoreactivity was decreased significantly in cell bodies of avulsed human DRG
      (n = 8, surgery delay 8 h to 12 months). There was a decrease in hIK1-like
      immunoreactivity predominantly in large cells acutely (<3 weeks after injury),
      but also in small/medium cells of chronic cases. Twenty-three injured peripheral
      nerves were studied (surgery delay 8 h to 12 months); in five of these, hIK1-like
      immunoreactivity was detected proximally but not distally to injury, whereas
      neurofilament staining confirmed the presence of nerve fibres in both regions.
      These five nerves, unlike the others, had all undergone Wallerian degeneration
      previously and the loss of hIK1-like immunoreactivity may therefore reflect
      reduced axonal transport of this ion channel across the injury site in
      regenerated fibres, as well as decreased expression in the cell body. In vitro
      studies of neonatal rat DRG neurones showed that nerve growth factor (NGF)
      significantly increased the percentage of hSK1-positive cells, whereas
      neurotrophin 3 (NT-3) and glial cell line-derived neurotrophic factor (GDNF)
      failed to show a significant effect. NT-3 stimulated hIK1 expression, while NGF
      and GDNF were ineffective. As expected, NGF increased expression of the voltage
      gated sodium channel SNS1/PN3 in this system. Decreased retrograde transport of
      these neurotrophic factors in injured sensory neurones may thus reduce expression
      of these ion channels and increase excitability. Blockade of IK1-like and other
      potassium channels by aminopyridines (4-AP and 3,4-DAP) may also explain the
      paraesthesiae induced by these medications. Selective potassium channel openers
      are likely to represent novel therapies for pain following nerve injury.

PMID- 11844727
TI  - Nerve granulomas and vasculitis in sarcoid peripheral neuropathy: a
      clinicopathological study of 11 patients.
AB  - Peripheral neuropathy is a rare, yet treatable manifestation of sarcoidosis, a
      multisystem disorder characterized by the presence of non-caseating granulomas
      that are seldom found in nerve biopsy specimens. In order to learn more about the
      subject, we reviewed our clinical and pathological findings in a series of 11
      patients (six men and five women aged 26-83 years) with symptomatic neuropathy
      associated with characteristic granulomas in nerve biopsy specimens. Only two
      patients were known to have sarcoidosis before the occurrence of the neuropathy.
      The neuropathy was focal or multifocal in six patients, including one with a
      multifocal neuropathy associated with conduction blocks, and one with a
      multifocal axonal motor deficit. Four patients had a distal symmetrical deficit
      and one patient had a Guillain-Barre-like syndrome with facial diplegia and
      respiratory failure. Serum angiotensin-converting enzyme concentration was
      elevated in only two patients. Epineurial granulomas and perineuritis were
      present in all nerve specimens. The inflammatory infiltrates invaded the
      endoneurium, following connective tissue septae and blood vessels, in five
      patients. Multinucleated giant cells were found in eight patients and necrotizing
      vasculitis in seven. Inflammatory lesions were associated with variable,
      asymmetrical involvement of nerve fascicles and axon loss. A muscle specimen was
      sampled during the same procedure in 10 patients. It showed inflammatory
      infiltrates and granulomas in nine patients and necrotizing vasculitis in two.
      Immunolabelling showed a mixed inflammatory infiltrate of T cells (predominantly
      CD4+ cells) and macrophages, in keeping with a delayed hypersensitivity reaction.
      In addition to nerve involvement, all patients had at least one other tissue or
      organ affected, including muscle in nine patients, lungs and/or intrathoracic
      lymph nodes in eight, skin in three, arthritis in two, and peripheral lymph
      nodes, stomach and eye in one patient each. Most patients improved on
      corticosteroids. Two patients remain free of symptoms after 7 years. Severe side
      effects of long-term treatment with corticosteroids occurred in two patients,
      leading to death in one. This study illustrates the wide range of clinical
      manifestations of sarcoid neuropathy and the frequent association of
      granulomatous inflammatory infiltrates with necrotizing vasculitis and with
      silent or symptomatic involvement of other organs.

PMID- 11844728
TI  - Attention to action in Parkinson's disease: impaired effective connectivity among
      frontal cortical regions.
AB  - The neural basis of attention to action was studied in 12 patients with
      Parkinson's disease (Hoehn and Yahr grades II and III) and 12 healthy age-matched
      controls. The subjects were studied by functional MRI (fMRI) during performance
      of a simple paced overlearned motor sequence task, with and without an additional
      attentional task. For the attentional task, subjects were instructed to attend
      either to their actions or to a visual distractor task. Statistical parametric
      mapping was used to implement a random effects analysis of the regional task
      related activations in patient and control populations. Structural equation
      modelling of fMRI time series was used to measure effective connectivity among
      prefrontal and premotor areas. In both groups, the motor task was associated with
      activation of a distributed network including the premotor, motor and parietal
      cortex, striatum and cerebellum. In control subjects, but not patients, attention
      to action (relative to execution of an overlearned sequence) was associated with
      further activation of prefrontal, parietal and paracingulate cortex, and the
      supplementary motor area (SMA). Patients with Parkinson's disease showed greater
      than normal activation of the SMA during execution of the simple overlearned
      motor sequence, but less augmentation when attending to their actions. In control
      subjects, attention to action, but not attention to the visual distractor task,
      increased the effective connectivity between prefrontal cortex and both the
      lateral premotor cortex and the SMA. This represents a specific increase in
      effective connectivity. Attentional modulation of effective connectivity between
      the prefrontal, premotor cortex and SMA was not observed in patients. This
      deficit indicates a context-specific functional disconnection between the
      prefrontal cortex and the supplementary and premotor cortex in Parkinson's
      disease.

PMID- 11844729
TI  - Movement control of manipulative tasks in patients with Gilles de la Tourette
      syndrome.
AB  - When a hand-held object is moved, grip and load force are accurately coordinated
      for establishing grasp stability. In the present work, the question was raised
      whether patients with Gilles de la Tourette syndrome (TS), who show tic-like
      movements, are impaired in grip-load force control when executing a manipulative
      task. To this end, we assessed force regulation during action patterns that
      required rhythmical unimanual or bimanual (iso-directional/anti-directional)
      movements. Results showed that the profile of grip-load force ratio was
      characterized by maxima and minima that were realized at upward and downward hand
      positions, respectively. TS patients showed increased force ratios during
      unimanual and bimanual movements, compared with control subjects, indicative of
      an inaccurate specification of the precision grip. Functional imaging data
      complemented the behavioural results and revealed that secondary motor areas
      showed no (or greatly reduced) activation in TS patients when executing the
      movement tasks as compared with baseline conditions. This indicates that the
      metabolic level in the secondary motor areas was equal during rest and task
      performance. At the neuronal level, this observation suggests that these cortical
      areas were continuously involved in movement preparation. Based on these data, we
      conclude that the ongoing activation of secondary motor areas may be explained by
      the TS patients' involuntary urges to move. Accordingly, interference will
      prevent an accurate planning of voluntary behaviour. Together, these findings
      reveal modulations in movement organization in patients with TS and exemplify
      degrading consequences for manual function.

PMID- 11844730
TI  - Motor cortex activation by transcranial magnetic stimulation in ataxia patients
      depends on the genetic defect.
AB  - In patients with degenerative ataxia, various abnormalities in motor cortex
      activation by transcranial magnetic stimulation (TMS) have been observed,
      including a reduction of intracortical facilitation and a lengthening of the
      silent period. However, the groups of patients examined in previous studies were
      heterogeneous, involving patients with autosomal-dominant and idiopathic
      cerebellar ataxia, and showing different clinical features. The aim of our
      present study was to investigate whether differences in motor cortex activation
      by TMS could be observed in genetically defined subtypes of degenerative ataxia.
      We examined six patients with Friedreich's ataxia, three patients with
      spinocerebellar ataxia (SCA) type 1, seven patients with SCA2, 12 patients with
      SCA3, nine patients with SCA6 and 14 healthy controls. In all subjects, motor
      threshold, central motor conduction time, cortical silent period after TMS, and
      intracortical inhibition and facilitation (as assessed by TMS using a paired
      pulses paradigm) were determined. Additionally, F wave amplitudes evoked by
      electrical peripheral nerve stimulation were measured. We found a significant
      reduction of intracortical facilitation in SCA2 and SCA3 patients. Furthermore,
      motor threshold was elevated in SCA1, central motor conduction time was
      lengthened in patients with Friedreich's ataxia and SCA1, and F wave amplitudes
      were enlarged in all the genetic subgroups except for SCA6. Silent period and
      intracortical inhibition did not differ between patients and controls. We
      conclude that changes of intracortical facilitation induced by TMS and other
      excitability parameters of the motor system are not a common phenomenon in
      degenerative ataxia, but are restricted to specific subtypes. This points to
      differences in the underlying pathophysiological processes in genetic subtypes of
      ataxia.

PMID- 11844731
TI  - Imaging how attention modulates pain in humans using functional MRI.
AB  - Current clinical and experimental literature strongly supports the phenomenon of
      reduced pain perception whilst attention is distracted away from noxious stimuli.
      This study used functional MRI to elucidate the underlying neural systems and
      mechanisms involved. An analogue of the Stroop task, the counting Stroop, was
      used as a cognitive distraction task whilst subjects received intermittent
      painful thermal stimuli. Pain intensity scores were significantly reduced when
      subjects took part in the more cognitively demanding interference task of the
      counting Stroop than in the less demanding neutral task. When subjects were
      distracted during painful stimulation, brain areas associated with the affective
      division of the anterior cingulate cortex (ACC) and orbitofrontal regions showed
      increased activation. In contrast, many areas of the pain matrix (i.e. thalamus,
      insula, cognitive division of the ACC) displayed reduced activation, supporting
      the behavioural results of reduced pain perception.

PMID- 11844732
TI  - In vivo evidence of altered skeletal muscle blood flow in chronic tension-type
      headache.
AB  - Painful impulses from tender pericranial muscles may play a major role in the
      pathophysiology of chronic tension-type headache. Firm evidence for peripheral
      muscle pathology as a cause of muscle pain and chronic headache is still lacking.
      Using a microdialysis technique, we aimed to estimate in vivo blood flow and
      interstitial lactate concentrations in the trapezius muscle at rest and during
      static exercise in patients with chronic tension-type headache and in healthy
      subjects. We recruited 16 patients with chronic tension-type headache and 17
      healthy control subjects. Two microdialysis catheters were inserted into the
      trapezius muscle (on the non-dominant side) of subjects, and dialysates were
      collected at rest, 15 and 30 min after the start of static exercise (10% of
      maximal force) and 15 and 30 min after the exercise was completed. All samples
      were coded and analysed blind. The primary endpoints were to detect a difference
      between patients and controls in changes of muscle blood flow and the
      interstitial lactate concentration from baseline to exercise and post-exercise
      periods. The increase in muscle blood flow from baseline to exercise and post
      exercise periods was significantly lower in patients than controls (P = 0.03).
      There was no difference in resting blood flow between patients and controls (P =
      0.43). Resting interstitial concentration of lactate did not differ between
      patients (2.51 +/- 0.18 mM; mean +/- standard error of the mean) and controls
      (2.35 +/- 0.23 mM, P = 0.57). There was no difference in change in interstitial
      lactate from baseline to exercise and post-exercise periods between patients and
      controls (P = 0.38). The present study provides in vivo evidence of decreased
      blood flow in response to static exercise in a tender muscle in patients with
      chronic tension-type headache. We suggest that, because of increased excitability
      of neurones in the CNS, the central interpretation and response to normal sensory
      input are altered in patients with chronic tension-type headache. This may lead
      to enhanced sympathetically mediated vasoconstriction and thereby a decreased
      blood flow in response to static exercise.

PMID- 11844733
TI  - Brain atrophy in clinically early relapsing-remitting multiple sclerosis.
AB  - Brain atrophy measured by MRI is a potentially useful tool for monitoring disease
      progression in multiple sclerosis. The location, extent and mechanisms of brain
      atrophy in early disease are not well documented. Using quantitative MRI, this
      study investigated whole brain, grey and white matter atrophy in clinically early
      relapsing-remitting multiple sclerosis and its relationship to lesion measures.
      Data came from 27 normal control subjects (14 females and 13 males, mean age 36.1
      years) and 26 subjects with clinically definite multiple sclerosis (18 females
      and eight males, mean age 35.1 years, mean delay from first symptom to scan 1.8
      years, median Expanded Disability Status Scale score 1.0). All had three
      dimensional fast spoiled gradient recall (3D FSPGR), T(1)-weighted pre- and post
      gadolinium-enhanced and T(2)-weighted scans. The 3D FSPGR images were
      automatically segmented into grey and white matter and cerebrospinal fluid using
      SPM99. 3D FSPGR hypo-intense, T(2) hyper-intense, T(1) hypo-intense and T(1) post
      gadolinium-enhancing lesion volumes were determined by semi-automatic lesion
      segmentation. The SPM99 output was combined with the 3D FSPGR lesion
      segmentations to quantify tissue volumes as fractions of total intracranial
      volumes, producing values for the brain parenchymal fraction (BPF), white matter
      fraction (WMF) and grey matter fraction (GMF). Comparing multiple sclerosis with
      control subjects, BPF, GMF and WMF were significantly reduced (P < 0.001 for all
      tissue fractions). Using Pearson correlations, T(2) hyper-intense and T(1) hypo
      intense lesion volumes were inversely related to BPF (T(2) r = -0.78, P < 0.001;
      T(1) r = -0.59, P = 0.002) and GMF (T(2) r = -0.73, P < 0.001; T(1) r = -0.53, P
      = 0.006), but not WMF (T(2) r = -0.30, P = 0.134; T(1) r = -0.26, P = 0.199).
      T(1) post-gadolinium-enhancing lesion volumes were not correlated with any
      fractional volumes. These results indicate that significant brain atrophy,
      affecting both grey and white matter, occurs early in the clinical course of
      multiple sclerosis. The lack of correlation between lesion load measures and WMF
      suggests that pathological changes in white matter may occur by mechanisms which
      are at least partly independent from overt lesion genesis in early multiple
      sclerosis.

PMID- 11844734
TI  - Oligodendrocyte precursor cells in the demyelinated multiple sclerosis spinal
      cord.
AB  - Lesions appearing in the CNS of patients in the chronic phase of the
      inflammatory, demyelinating disease multiple sclerosis often fail to repair,
      resulting in neurological dysfunction. This failure of remyelination appears, in
      many cases, to be due not to the destruction of the local oligodendrocyte
      precursor population, a source for new myelin-forming cells, but to the failure
      of the precursor cells to proliferate and differentiate, at least in brain
      lesions. The spinal cord is also a prominent site for lesions in multiple
      sclerosis, but nothing is known about the fate of the oligodendrocyte precursor
      population in this area. The present study has therefore analysed spinal cord
      samples with demyelination from 16 subjects with longstanding multiple sclerosis
      for the presence of oligodendrocyte precursor cells. Immunolabellings of 10
      microm thick sections with the O4/anti-galactocerebroside (GalC) antibody
      combination, to visualize O4-positive, GalC-negative oligodendrocyte precursor
      cells, revealed that such cells were prevalent in many spinal cord lesions, with
      densities of up to 35 cells/mm(2). Six of the spinal cord lesions contained < or
      =3 O4-positive, GalC-negative cells/mm(2), but such cells were widespread in
      brain lesions from these multiple sclerosis cases that were available for study
      (8-26 cells/mm(2)). The density of the O4-positive, GalC-negative oligodendrocyte
      precursor cells in all spinal cord and brain lesions studied thus far (n = 41)
      decreased significantly with declining numbers of debris-laden macrophages. In
      addition, lesions lacking macrophages tended to be derived from the older
      patients and there was a negative correlation between the density of the
      oligodendrocyte precursor cells and clinical age of the multiple sclerosis
      subject at death, and disease duration. The analysis further revealed that
      lesions from subjects with primary progressive and secondary progressive multiple
      sclerosis contained, on average, similar numbers of oligodendrocyte precursor
      cells/mm(2) and that immature oligodendrocytes were only present in significant
      numbers in lesions with high precursor densities. Taken together, the present
      data suggest that there is a gradual reduction in the size of the O4-positive,
      GalC- negative oligodendrocyte precursor population with increasing age of the
      lesion, that the generation of new oligodendrocytes becomes increasingly more
      impaired and that lesions are not repopulated to a significant extent by
      migratory oligodendrocyte precursor cells present in the adjacent unaffected
      tissue. Hence, strategies intended to promote endogenous remyelination in
      multiple sclerosis patients should focus on both enhancing the long-term survival
      of oligodendrocyte precursor cells and on stimulating these cells to proliferate
      and differentiate into remyelinating oligodendrocytes.

PMID- 11844735
TI  - The subcortical anatomy of human spatial neglect: putamen, caudate nucleus and
      pulvinar.
AB  - Various studies have documented that right hemispheric lesions restricted to the
      basal ganglia or to the thalamus may evoke spatial neglect. However, for
      methodological reasons, the exact anatomical correlate of spatial neglect within
      these two subcortical structures still remained uncertain. The present study
      identified these locations by comparing the anatomy of subcortical lesions to the
      basal ganglia or thalamus between neglect and control patients. Analysis revealed
      that the putamen, the pulvinar and, to a smaller degree, the caudate nucleus are
      the subcortical structures typically associated with spatial neglect in humans.
      All these structures have direct anatomical connections to the superior temporal
      gyrus (STG), which recently has been identified as the neural correlate of
      spatial neglect in the human cortex. Therefore, it is assumed that the right
      putamen, caudate nucleus, pulvinar and STG form a coherent corticosubcortical
      anatomical network in the genesis of spatial neglect in humans.

PMID- 11844736
TI  - Late plasticity for language in a child's non-dominant hemisphere: a pre- and
      post-surgery fMRI study.
AB  - The ability of the right hemisphere to sustain the acquisition or the recovery of
      language after extensive damage to the left hemisphere has been essentially
      related to the age at the time of injury. Better language abilities are acquired
      when the insult occurs in early childhood (perinatal insults) compared with later
      occurrence. However, while previous studies have described the neuropsychological
      pattern of language development in typical cases, the neural bases of such
      plasticity remain unexplored. Non-invasive functional MRI (fMRI) is a unique tool
      to assess the neural correlates of brain plasticity through repeated studies, but
      the technique has not been widely used in children because of methodological
      limitations. Plasticity of language was studied in a boy who developed
      intractable epilepsy related to Rasmussen's syndrome of the left hemisphere at
      age 5 years 6 months, after normal language acquisition. The first fMRI study at
      age 6 years 10 months showed left lateralization of language networks during a
      word fluency task. After left hemispherotomy at age 9 years, the child
      experienced profound aphasia and alexia, with rapid recovery of receptive
      language but slower and incomplete recovery of expressive language and reading.
      Postoperative fMRI at age 10 years 6 months showed a shift of language-related
      networks to the right during expressive and receptive tasks. Right activation was
      seen mainly in regions that could not be detected preoperatively, but mirrored
      those previously found in the left hemisphere (inferior frontal, temporal and
      parietal cortex), suggesting reorganization in a pre-existing bilateral network.
      In addition, neuropsychological data of this case support the hypothesis of
      innately more bilateral distribution of receptive than expressive language. This
      first serial fMRI study illustrates the great plasticity of the child's brain and
      the ability of the right hemisphere to take over some expressive language
      functions, even at a relatively late age. It also suggests a limit for removal of
      the dominant hemisphere beyond the age of 6 years, a classical limit for the
      critical period of language acquisition.

PMID- 11844737
TI  - Power and coherence of sleep spindle frequency activity following hemispheric
      stroke.
AB  - Brainstem and thalamic structures are known to play a critical role in modulating
      sleep-wake cycles, but the extent to which the cerebral hemispheres are involved
      remains unclear. To study the role of the cerebral hemispheres in generating
      sleep EEG patterns, all-night polysomnographic recordings were collected in
      subjects with brain damage (n = 30) caused by hemispheric stroke and in
      hospitalized controls (n = 12). Recordings were made in the acute (< or =10 days
      post-stroke), subchronic (11-35 days post-stroke) and chronic (>60 days post
      stroke) phases of stroke. Bipolar and referential EEG derivations were recorded.
      Standard sleep stage scoring was conducted using the referential derivation
      placed opposite the lesion. Sleep stage 2 power and coherence spectra were
      calculated based on recordings from bipolar derivations. In the mean spectra, the
      highest spindle frequency peak was identified and its size was calculated
      relative to the background spectrum. Analysis of visually scored EEG data
      indicated that, compared with controls, acute phase brain-damaged subjects had
      lower sleep efficiency and increased waking after sleep onset. The durations of
      rapid eye movement and non-rapid eye movement sleep stages did not differ
      significantly between brain-damaged subjects and hospitalized controls. Spectral
      analyses revealed that, compared with hospitalized controls, brain-damaged
      subjects had significantly reduced spindle peak sizes in the power and coherence
      spectra from derivations ipsilateral to the lesion. Within-subject comparisons
      across time demonstrated that the power and coherence of sleep spindle frequency
      activity increased significantly from the acute to the chronic phases of stroke,
      suggesting that plastic mechanisms allowed the possibility of recovery. Our
      findings provide novel evidence that the cerebral hemispheres are important in
      generating coherent sleep spindles in humans, and they are consonant with prior
      empirical and theoretical evidence that corticothalamic projections modulate the
      generation of synchronous spindle oscillations. Because spindle oscillations are
      thought to be involved in blocking sensory input to the cortex during sleep, the
      decrease in synchronous spindle frequency activity following hemispheric stroke
      may contribute to the observed reduction in sleep continuity.

PMID- 11844738
TI  - Twin-singleton differences in brain structure using structural equation
      modelling.
AB  - Twin studies are important to investigate genetic influences on variation in
      human brain morphology in health and disease. However, the twin method has been
      criticized for its alleged non-generalizability due to differences in the
      intrauterine and family environment of twins, compared with singletons. To test
      whether twin-singleton differences complicate interpretation of genetic
      contributions on variation in brain volume, brains from 112 pairs of twins and 34
      of their siblings with a mean (standard deviation) age of 30.7 (9.6) years were
      scanned using MRI. The influence of birth order, zygosity and twin-sibling
      differences on brain volume measures was analysed using maximum-likelihood model
      fitting. Variances were homogeneous across birth order, zygosity and twin
      singleton status. Irrespective of zygosity, intracranial volume was smaller in
      second-born twins compared with first-born twins and compared with siblings. Grey
      matter volume was smaller in second-born twins compared with first-born twins.
      White matter was smaller in twins compared with siblings. Differences in grey and
      white matter between these groups were no longer significant after correction for
      intracranial volume. Total brain, and lateral and third ventricle volumes were
      comparable in twins and singletons. In conclusion, second-born twins have a
      smaller intracranial volume than their first-born co-twins and siblings. This
      suggests aberrant early brain development in second-born twins, which is
      consistent with the suboptimal pre- and perinatal environment related to birth
      order in twins. Since other brain volume measures were comparable between the
      groups, twin studies can provide reliable estimates of heritabilities in brain
      volume measures and these can be generalized to the singleton population.

PMID- 11844739
TI  - Visual hallucinations in Lewy body disease relate to Lewy bodies in the temporal
      lobe.
AB  - Consensus opinion characterizes dementia with Lewy bodies (DLB) as a progressive
      dementing illness, with significant fluctuations in cognition, visual
      hallucinations and/or parkinsonism. When parkinsonism is an early dominant
      feature, consensus opinion recommends that dementia within the first year is
      necessary for a diagnosis of DLB. If dementia occurs later, a diagnosis of
      Parkinson's disease with dementia (PDD) is recommended. While many previous
      studies have correlated the neuropathology in DLB with dementia and parkinsonism,
      few have analysed the relationship between fluctuating cognition and/or well
      formed visual hallucinations and the underlying neuropathology in DLB and PDD.
      The aim of the present study was to determine any relationship between these less
      studied core clinical features of DLB, and the distribution and density of
      cortical Lewy bodies (LB). The brains of 63 cases with LB were obtained over 6
      years following population-based studies of dementia and parkinsonian syndromes.
      Annual, internationally standardized, clinical assessment batteries were reviewed
      to determine the presence and onset of the core clinical features of DLB. The
      maximal density of LB, plaques and tangles in the amygdala, parahippocampal,
      anterior cingulate, superior frontal, inferior temporal, inferior parietal and
      visual cortices were determined. Current clinicopathological diagnostic criteria
      were used to classify cases into DLB (n = 29), PDD (n = 18) or parkinsonism
      without dementia (n = 16) groups. Predictive statistics were used to ascertain
      whether fluctuating cognition or visual hallucinations predicted the
      clinicopathological group. Analysis of variance and regressions were used to
      identify any significant relationship(s) between the presence and severity of
      neuropathological and clinical features. Cognitive fluctuations and/or visual
      hallucinations were not good predictors of DLB in pathologically proven patients,
      although the absence of these features early in the disease course was highly
      predictive of PDD. Cases with DLB had higher LB densities in the inferior
      temporal cortex than cases with PDD. There was no association across groups
      between any neuropathological variable and the presence or absence of fluctuating
      cognition. However, there was a striking association between the distribution of
      temporal lobe LB and well-formed visual hallucinations. Cases with well-formed
      visual hallucinations had high densities of LB in the amygdala and
      parahippocampus, with early hallucinations relating to higher densities in
      parahippocampal and inferior temporal cortices. These temporal regions have
      previously been associated with visual hallucinations in other disorders. Thus,
      our results suggest that the distribution of temporal lobe LB is more related to
      the presence and duration of visual hallucinations in cases with LB than to the
      presence, severity or duration of dementia.

PMID- 11844740
TI  - Inhibitory control of acquired motor programmes in the human brain.
AB  - An important basis of skilled human behaviour is the appropriate retrieval of
      acquired and memorized motor programmes ('motor memory traces'). Appropriate
      retrieval is warranted if motor programmes are only activated if necessary and
      are, probably more often, inhibited if required by the context of a given
      situation. It is unknown how this type of inhibition is accomplished in the
      brain. We studied context-dependent modulation of motor memory traces in 18
      volunteers and six patients with focal dystonia. Cortical function was assessed
      with transcranial magnetic stimulation over the primary motor cortex (M1) and
      with task-related analysis of oscillatory EEG activity. An activation (ACT) and
      inhibition (INH) condition were compared. In both, visual cues were presented at
      1/s. In ACT, subjects had to respond to these cues with individual finger
      movements as learned in a preceding training session. In INH, subjects had to
      observe the cues without retrieval of motor responses. During INH, inhibitory
      control of the motor memory trace was confirmed by significant amplitude
      reduction of motor evoked potentials (MEPs) compared with baseline. This was
      accompanied by a significant increase of 11-13 Hz oscillatory activity over the
      sensorimotor areas during INH. During active retrieval of the motor memory
      traces, the reverse was true (increased MEP amplitudes, decreased oscillatory 11
      13 Hz activity). In a small sample of dystonic patients (n = 6), the increase of
      11-13 Hz oscillatory activity during INH was consistently absent. The present
      data demonstrate for the first time cortical correlates of appropriate, context
      dependent inhibition of motor memory traces. We propose that focal increases of
      oscillatory activity are instrumental for inhibitory control at the cortical
      level. This concept is supported by the preliminary observations in dystonic
      patients who are known to have deficits of inhibitory motor control and in whom
      these context-dependent focal increases of oscillatory activity were absent.

PMID- 11844741
TI  - Oscillatory mechanism in primary sensory neurones.
AB  - Ectopic spike activity, generated at low levels in intact sensory dorsal root
      ganglia and intensified following axotomy, is an important cause of neuropathic
      pain. The spikes are triggered by subthreshold membrane potential oscillations.
      The depolarizing phase of oscillation sinusoids is due to a phasic voltage
      sensitive Na(+) conductance (gNa(+)). Here we examine the repolarizing phase for
      which K(+) conductance (gK(+)) is implicated. In vivo, gK(+) blockers have
      excitatory effects inconsistent with the elimination of oscillations. Indeed,
      using excised dorsal root ganglia in vitro, we found that gK(+) block does not
      eliminate oscillations; on the contrary, it has a variety of facilitatory
      effects. However, oscillations were eliminated by shifting the K(+) reversal
      potential so as to neutralize voltage-insensitive K(+) leak channels. Based on
      these data, we propose a novel oscillatory model: oscillation sinusoids are due
      to reciprocation between a phasically activating voltage-dependent, tetrodotoxin
      sensitive Na(+) conductance and passive, voltage-independent K(+) leak. In drug
      free media, voltage-sensitive K(+) channels act to suppress oscillations and
      increase their frequency. Numerical simulations support this model and account
      for the effects of gK(+) block. Oscillations in dorsal root ganglia neurones
      appear to be based on the simplest possible configuration of ionic conductances
      compatible with sustained high frequency oscillatory behaviour. The oscillatory
      mechanism might be exploited in the search for novel analgesic drugs.

PMID- 11844742
TI  - Orexins in the brain-gut axis.
AB  - Orexins (hypocretins) are a novel pair of neuropeptides implicated in the
      regulation of energy balances and arousal. Previous reports have indicated that
      orexins are produced only in the lateral hypothalamic area, although orexin
      containing nerve fibers were observed throughout the neuroaxis. Recent evidence
      shows that orexins and functional orexin receptors are found in the periphery.
      Vagal and spinal primary afferent neurons, enteric neurons, and endocrine cells
      in both the gut and pancreas display orexin- and orexin receptor-like
      immunoreactivity. Orexins excite secretomotor neurons in the guinea pig gut and
      modulate gastric and intestinal motility and secretion. In addition, orexins
      modulate hormone release from pancreatic endocrine cells. Moreover, fasting up
      regulates the phosphorylated form of cAMP response element binding protein in
      orexin-immunoreactive enteric neurons, indicating a functional response to food
      status in these cells. The purpose of this article is to summarize evidence for
      the existence of a brain-gut network of orexin-containing cells that appears to
      play a role in the acute regulation of energy homeostasis.

PMID- 11844743
TI  - Antiresorptive treatment of postmenopausal osteoporosis: comparison of study
      designs and outcomes in large clinical trials with fracture as an endpoint.
AB  - Antiresorptive treatments for postmenopausal osteoporosis have been studied
      extensively, but due to the volume of published data and lack of head-to-head
      trials, it is difficult to evaluate and compare their fracture reduction
      efficacy. The objective of this review is to summarize the results from clinical
      trials that have fracture as an endpoint and to discuss the factors in study
      design and populations that can affect the interpretation of the results.
      Although there are numerous observational studies suggesting that estrogen and
      hormone replacement therapies may reduce the risk of vertebral and nonvertebral
      fractures, there is no large, prospective, randomized, placebo-controlled, double
      blind clinical trial demonstrating fracture efficacy. The effects of raloxifene,
      alendronate, risedronate, and salmon calcitonin on increasing bone mineral
      density (BMD) and decreasing fracture risk have been shown in randomized, placebo
      controlled, double-blind clinical trials of postmenopausal women with
      osteoporosis. Although the increases in lumbar spine BMD vary greatly in these
      trials, the decrease in relative risk of vertebral fractures is similar among
      therapies. However, nonvertebral fracture efficacy has not been consistently
      demonstrated. Combined administration of two antiresorptive therapies results in
      greater BMD increases, but the effects on fracture risk are unknown. Direct
      comparisons of clinical trial results should be considered carefully, given the
      differences in study design and populations. Differences in study design that may
      influence the efficacy of fracture risk reduction include calcium and vitamin D
      supplementation, primary fracture endpoints, definition of vertebral deformity or
      fracture, discontinuation rates, and statistical power. Factors in the study
      population that may influence fracture efficacy include the age of the population
      and the proportion of subjects with prevalent fractures. The use of surrogate
      endpoints such as BMD to predict fracture risk should be approached with caution,
      as the relationship between BMD changes and fracture risk reduction with
      antiresorptive therapies is uncertain. Consideration of these results from
      clinical trials can contribute to clinical judgment in selecting the best
      treatment option for postmenopausal osteoporosis.

PMID- 11844744
TI  - Biochemistry, cellular and molecular biology, and physiological roles of the
      iodothyronine selenodeiodinases.
AB  - The goal of this review is to place the exciting advances that have occurred in
      our understanding of the molecular biology of the types 1, 2, and 3 (D1, D2, and
      D3, respectively) iodothyronine deiodinases into a biochemical and physiological
      context. We review new data regarding the mechanism of selenoprotein synthesis,
      the molecular and cellular biological properties of the individual deiodinases,
      including gene structure, mRNA and protein characteristics, tissue distribution,
      subcellular localization and topology, enzymatic properties, structure-activity
      relationships, and regulation of synthesis, inactivation, and degradation. These
      provide the background for a discussion of their role in thyroid physiology in
      humans and other vertebrates, including evidence that D2 plays a significant role
      in human plasma T(3) production. We discuss the pathological role of D3
      overexpression causing "consumptive hypothyroidism" as well as our current
      understanding of the pathophysiology of iodothyronine deiodination during illness
      and amiodarone therapy. Finally, we review the new insights from analysis of mice
      with targeted disruption of the Dio2 gene and overexpression of D2 in the
      myocardium.

PMID- 11844745
TI  - Changes in proinflammatory cytokine activity after menopause.
AB  - There is now a large body of evidence suggesting that the decline in ovarian
      function with menopause is associated with spontaneous increases in
      proinflammatory cytokines. The cytokines that have obtained the most attention
      are IL-1, IL-6, and TNF-alpha. The exact mechanisms by which estrogen interferes
      with cytokine activity are still incompletely known but may potentially include
      interactions of the ER with other transcription factors, modulation of nitric
      oxide activity, antioxidative effects, plasma membrane actions, and changes in
      immune cell function. Experimental and clinical studies strongly support a link
      between the increased state of proinflammatory cytokine activity and
      postmenopausal bone loss. Preliminary evidence suggests that these changes also
      might be relevant to vascular homeostasis and the development of atherosclerosis.
      Better knowledge of the mechanisms and the time course of these interactions may
      open new avenues for the prevention and treatment of some of the most prevalent
      and important disorders in postmenopausal women.

PMID- 11844747
TI  - Turner's syndrome in adulthood.
AB  - Turner's syndrome is the most common chromosomal abnormality in females,
      affecting 1:2,500 live female births. It is a result of absence of an X
      chromosome or the presence of a structurally abnormal X chromosome. Its most
      consistent clinical features are short stature and ovarian failure. However, it
      is becoming increasingly evident that adults with Turner's syndrome are also
      susceptible to a range of disorders, including osteoporosis, hypothyroidism, and
      renal and gastrointestinal disease. Women with Turner's syndrome have a reduced
      life expectancy, and recent evidence suggests that this is due to an increased
      risk of aortic dissection and ischemic heart disease. Up until recently, women
      with Turner's syndrome did not have access to focused health care, and thus
      quality of life was reduced in a significant number of women. All adults with
      Turner's syndrome should therefore be followed up by a multidisciplinary team to
      improve life expectancy and reduce morbidity.

PMID- 11844751
TI  - The flavoprotein MrsD catalyzes the oxidative decarboxylation reaction involved
      in formation of the peptidoglycan biosynthesis inhibitor mersacidin.
AB  - The lantibiotic mersacidin inhibits peptidoglycan biosynthesis by binding to the
      peptidoglycan precursor lipid II. Mersacidin contains an unsaturated thioether
      bridge, which is proposed to be synthesized by posttranslational modifications of
      threonine residue +15 and the COOH-terminal cysteine residue of the mersacidin
      precursor peptide MrsA. We show that the flavoprotein MrsD catalyzes the
      oxidative decarboxylation of the COOH-terminal cysteine residue of MrsA to an
      aminoenethiol residue. MrsD belongs to the recently described family of homo
      oligomeric flavin-containing Cys decarboxylases (i.e., the HFCD protein family).
      Members of this protein family include the bacterial Dfp proteins (which are
      involved in coenzyme A biosynthesis), eukaryotic salt tolerance proteins, and
      further oxidative decarboxylases such as EpiD. In contrast to EpiD and Dfp, MrsD
      is a FAD and not an FMN-dependent flavoprotein. HFCD enzymes are characterized by
      a conserved His residue which is part of the active site. Exchange of this His
      residue for Asn led to inactivation of MrsD. The lantibiotic-synthesizing enzymes
      EpiD and MrsD have different substrate specificities.

PMID- 11844750
TI  - Mechanism of coupling of transport to hydrolysis in bacterial ATP-binding
      cassette transporters.

PMID- 11844752
TI  - Shigella Spa32 is an essential secretory protein for functional type III
      secretion machinery and uniformity of its needle length.
AB  - The Shigella type III secretion machinery is responsible for delivering to host
      cells the set of effectors required for invasion. The type III secretion complex
      comprises a needle composed of MxiH and MxiI and a basal body made up of MxiD,
      MxiG, and MxiJ. In S. flexneri, the needle length has a narrow range, with a mean
      of approximately 45 nm, suggesting that it is strictly regulated. Here we show
      that Spa32, encoded by one of the spa genes, is an essential protein translocated
      via the type III secretion system and is involved in the control of needle length
      as well as type III secretion activity. When the spa32 gene was mutated, the type
      III secretion complexes possessed needles of various lengths, ranging from 40 to
      1,150 nm. Upon introduction of a cloned spa32 into the spa32 mutant, the bacteria
      produced needles of wild-type length. The spa32 mutant overexpressing MxiH
      produced extremely long (>5 microm) needles. Spa32 was secreted into the medium
      via the type III secretion system, but secretion did not depend on activation of
      the system. The spa32 mutant and the mutant overexpressing MxiH did not secrete
      effectors such as Ipa proteins into the medium or invade HeLa cells. Upon
      introduction of Salmonella invJ, encoding InvJ, which has 15.4% amino acid
      identity with Spa32, into the spa32 mutant, the bacteria produced type III
      needles of wild-type length and efficiently entered HeLa cells. These findings
      suggest that Spa32 is an essential secreted protein for a functional type III
      secretion system in Shigella spp. and is involved in the control of needle
      length. Furthermore, its function is interchangeable with that of Salmonella
      InvJ.

PMID- 11844753
TI  - PduA is a shell protein of polyhedral organelles involved in coenzyme B(12)
      dependent degradation of 1,2-propanediol in Salmonella enterica serovar
      typhimurium LT2.
AB  - Salmonella enterica forms polyhedral organelles involved in coenzyme B(12)
      dependent 1,2-propanediol degradation. These organelles are thought to consist of
      a proteinaceous shell that encases coenzyme B(12)-dependent diol dehydratase and
      perhaps other enzymes involved in 1,2-propanediol degradation. The function of
      these organelles is unknown, and no detailed studies of their structure have been
      reported. Genes needed for organelle formation and for 1,2-propanediol
      degradation are located at the 1,2-propanediol utilization (pdu) locus, but the
      specific genes involved in organelle formation have not been identified. Here, we
      show that the pduA gene encodes a shell protein required for the formation of
      polyhedral organelles involved in coenzyme B(12)-dependent 1,2-propanediol
      degradation. A His(6)-PduA fusion protein was purified from a recombinant
      Escherichia coli strain and used for the preparation of polyclonal antibodies.
      The anti-PduA antibodies obtained were partially purified by a subtraction
      procedure and used to demonstrate that the PduA protein localized to the shell of
      the polyhedral organelles. In addition, electron microscopy studies established
      that strains with nonpolar pduA mutations were unable to form organelles. These
      results show that the pduA gene is essential for organelle formation and indicate
      that the PduA protein is a structural component of the shell of these organelles.
      Physiological studies of nonpolar pduA mutants were also conducted. Such mutants
      grew similarly to the wild-type strain at low concentrations of 1,2-propanediol
      but exhibited a period of interrupted growth in the presence of higher
      concentrations of this growth substrate. Growth tests also showed that a nonpolar
      pduA deletion mutant grew faster than the wild-type strain at low vitamin B(12)
      concentrations. These results suggest that the polyhedral organelles formed by S.
      enterica during growth on 1,2-propanediol are not involved in the concentration
      of 1,2-propanediol or coenzyme B(12), but are consistent with the hypothesis that
      these organelles moderate aldehyde production to minimize toxicity.

PMID- 11844754
TI  - Reconstitution of the trimethylamine oxide reductase regulatory elements of
      Shewanella oneidensis in Escherichia coli.
AB  - Several bacteria can grow by using small organic compounds such as trimethylamine
      oxide (TMAO) as electron acceptors. In Shewanella species, the TMAO reductase
      respiratory system is encoded by the torECAD operon. We showed that production of
      the TMAO reductase of S. oneidensis was induced by TMAO and repressed by oxygen,
      and we noticed that a three-gene cluster (torSTR) encoding a complex two
      component regulatory system was present downstream of the torECAD operon. We
      introduced the torSTR gene cluster into Escherichia coli and showed that this
      regulatory gene cluster is involved in TMAO induction of the torE promoter but
      plays no role in the oxygen control. The TorR response regulator was purified,
      and gel shift and footprinting experiments revealed that TorR binds to a single
      region located about 70 bases upstream of the transcription start site of the tor
      structural operon. By deletion analysis, we confirmed that the TorR operator site
      is required for induction of the tor structural promoter. As the TMAO regulatory
      system of S. oneidensis is homologous to that of E. coli, we investigated a
      possible complementation between the TMAO regulatory components of the two
      bacteria. Interestingly, TorS(ec), the TMAO sensor of E. coli, was able to
      transphosphorylate TorR(so), the TMAO response regulator of S. oneidensis.

PMID- 11844755
TI  - Salmonella enterica serovar typhimurium resistance to bile: identification and
      characterization of the tolQRA cluster.
AB  - Salmonella enterica serovar Typhimurium is resistant to the action of bile salts,
      and resistance to bile is enhanced in strains in which the PhoP-PhoQ (PhoPQ) two
      component regulatory system has been activated. To identify genes necessary for
      bile resistance, MudJ transposon mutagenesis was performed on a strain containing
      a phoP mutation that results in constitutive expression of PhoP-activated genes.
      After screening >10,000 mutants for the loss of growth on Luria-Bertani broth
      bile plates, 14 bile-sensitive mutants were identified. Of these 14 mutants, 3
      were found to retain the bile sensitivity phenotype upon P22 transduction, to
      possess wild-type growth characteristics, and to contain a smooth
      lipopolysaccharide. Southern hybridization experiments showed that all three
      strains contained unique insertions. DNA sequencing of the transposon-chromosomal
      DNA fusion junctions of these strains showed all to be linked to the putative
      Salmonella orf1-tolQRA operon, with insertions in tolQ, orf1, and a gene upstream
      of the orf1-tolQRA operon not previously associated with Tol function (orfX).
      Through the use of transcriptional fusions, none of the putative tol (or tol
      associated) genes were shown to be regulated by PhoPQ, bile, or the RcsC-RcsB two
      component system; however, all of the genes (orfX, orf1, tolQRA) are predicted to
      be cotranscribed. This is the first identification of Salmonella serovar
      Typhimurium Tol homologs and the first demonstration of their role in bile
      resistance in this organism. In addition, the observed regulation, operon
      arrangement, and phenotypes associated with these tol genes demonstrate
      significant differences from their Escherichia coli homologs.

PMID- 11844756
TI  - Corynebacterium glutamicum utilizes both transsulfuration and direct
      sulfhydrylation pathways for methionine biosynthesis.
AB  - A direct sulfhydrylation pathway for methionine biosynthesis in Corynebacterium
      glutamicum was found. The pathway was catalyzed by metY encoding O
      acetylhomoserine sulfhydrylase. The gene metY, located immediately upstream of
      metA, was found to encode a protein of 437 amino acids with a deduced molecular
      mass of 46,751 Da. In accordance with DNA and protein sequence data, the
      introduction of metY into C. glutamicum resulted in the accumulation of a 47-kDa
      protein in the cells and a 30-fold increase in O-acetylhomoserine sulfhydrylase
      activity, showing the efficient expression of the cloned gene. Although
      disruption of the metB gene, which encodes cystathionine gamma-synthase
      catalyzing the transsulfuration pathway of methionine biosynthesis, or the metY
      gene was not enough to lead to methionine auxotrophy, an additional mutation in
      the metY or the metB gene resulted in methionine auxotrophy. The growth pattern
      of the metY mutant strain was identical to that of the metB mutant strain,
      suggesting that both methionine biosynthetic pathways function equally well. In
      addition, an Escherichia coli metB mutant could be complemented by transformation
      of the strain with a DNA fragment carrying corynebacterial metY and metA genes.
      These data clearly show that C. glutamicum utilizes both transsulfuration and
      direct sulfhydrylation pathways for methionine biosynthesis. Although metY and
      metA are in close proximity to one another, separated by 143 bp on the
      chromosome, deletion analysis suggests that they are expressed independently. As
      with metA, methionine could also repress the expression of metY. The repression
      was also observed with metB, but the degree of repression was more severe with
      metY, which shows almost complete repression at 0.5 mM methionine in minimal
      medium. The data suggest a physiologically distinctive role of the direct
      sulfhydrylation pathway in C. glutamicum.

PMID- 11844757
TI  - YopD and LcrH regulate expression of Yersinia enterocolitica YopQ by a
      posttranscriptional mechanism and bind to yopQ RNA.
AB  - Pathogenic yersiniae secrete 14 Yop proteins via the type III pathway. Synthesis
      of YopQ occurs when the type III machinery is activated by a low-calcium signal,
      but not when the calcium concentration is above 100 microM. To characterize the
      mechanism that regulates the expression of yopQ, mutants that permit synthesis of
      YopQ in the presence of calcium were isolated. Yersiniae bearing deletion
      mutations in yopN, tyeA, sycN, or yscB synthesized and secreted YopQ in both the
      presence and the absence of calcium. In contrast, yersiniae with a deletion in
      yopD or lcrH synthesized YopQ in the presence of calcium but did not secrete the
      polypeptide. These variants displayed no defect in YopQ secretion under low
      calcium conditions, revealing that yopD and lcrH are required for the regulation
      of yopQ expression. Experiments with transcriptional and translational fusions to
      the npt reporter gene suggest that yopD and lcrH regulate yopQ expression at a
      posttranscriptional step. YopD and LcrH form a complex in the bacterial cytosol
      and bind yopQ mRNA. Models that can account for posttranscriptional regulatory
      mechanisms of yop expression are discussed.

PMID- 11844758
TI  - Amino acid- and purine ribonucleoside-induced germination of Bacillus anthracis
      DeltaSterne endospores: gerS mediates responses to aromatic ring structures.
AB  - Specific combinations of amino acids or purine ribonucleosides and amino acids
      are required for efficient germination of endospores of Bacillus anthracis
      DeltaSterne, a plasmidless strain, at ligand concentrations in the low-micromolar
      range. The amino acid L-alanine was the only independent germinant in B.
      anthracis and then only at concentrations of >10 mM. Inosine and L-alanine both
      play major roles as cogerminants with several other amino acids acting as
      efficient cogerminants (His, Pro, Trp, and Tyr combining with L-alanine and Ala,
      Cys, His, Met, Phe, Pro, Ser, Trp, Tyr, and Val combining with inosine). An
      ortholog to the B. subtilis tricistronic germination receptor operon gerA was
      located on the B. anthracis chromosome and named gerS. Disruption of gerS
      completely eliminated the ability of B. anthracis endospores to respond to amino
      acid and inosine-dependent germination responses. The gerS mutation also produced
      a significant microlag in the aromatic-amino-acid-enhanced-alanine germination
      pathways. The gerS disruption appeared to specifically affect use of aromatic
      chemicals as cogerminants with alanine and inosine. We conclude that efficient
      germination of B. anthracis endospores requires multipartite signals and that
      gerS-encoded proteins act as an aromatic-responsive germination receptor.

PMID- 11844760
TI  - Periplasmic nitrate reductase (NapABC enzyme) supports anaerobic respiration by
      Escherichia coli K-12.
AB  - Periplasmic nitrate reductase (NapABC enzyme) has been characterized from a
      variety of proteobacteria, especially Paracoccus pantotrophus. Whole-genome
      sequencing of Escherichia coli revealed the structural genes napFDAGHBC, which
      encode NapABC enzyme and associated electron transfer components. E. coli also
      expresses two membrane-bound proton-translocating nitrate reductases, encoded by
      the narGHJI and narZYWV operons. We measured reduced viologen-dependent nitrate
      reductase activity in a series of strains with combinations of nar and nap null
      alleles. The napF operon-encoded nitrate reductase activity was not sensitive to
      azide, as shown previously for the P. pantotrophus NapA enzyme. A strain carrying
      null alleles of narG and narZ grew exponentially on glycerol with nitrate as the
      respiratory oxidant (anaerobic respiration), whereas a strain also carrying a
      null allele of napA did not. By contrast, the presence of napA+ had no influence
      on the more rapid growth of narG+ strains. These results indicate that
      periplasmic nitrate reductase, like fumarate reductase, can function in anaerobic
      respiration but does not constitute a site for generating proton motive force.
      The time course of phi(napF-lacZ) expression during growth in batch culture
      displayed a complex pattern in response to the dynamic nitrate/nitrite ratio. Our
      results are consistent with the observation that phi(napF-lacZ) is expressed
      preferentially at relatively low nitrate concentrations in continuous cultures
      (H. Wang, C.-P. Tseng, and R. P. Gunsalus, J. Bacteriol. 181:5303-5308, 1999).
      This finding and other considerations support the hypothesis that NapABC enzyme
      may function in E. coli when low nitrate concentrations limit the bioenergetic
      efficiency of nitrate respiration via NarGHI enzyme.

PMID- 11844759
TI  - Allelic diversity and population structure in Vibrio cholerae O139 Bengal based
      on nucleotide sequence analysis.
AB  - Comparative analysis of gene fragments of six housekeeping loci, distributed
      around the two chromosomes of Vibrio cholerae, has been carried out for a
      collection of 29 V. cholerae O139 Bengal strains isolated from India during the
      first epidemic period (1992 to 1993). A toxigenic O1 ElTor strain from the
      seventh pandemic and an environmental non-O1/non-O139 strain were also included
      in this study. All loci studied were polymorphic, with a small number of
      polymorphic sites in the sequenced fragments. The genetic diversity determined
      for our O139 population is concordant with a previous multilocus enzyme
      electrophoresis study in which we analyzed the same V. cholerae O139 strains. In
      both studies we have found a higher genetic diversity than reported previously in
      other molecular studies. The results of the present work showed that O139 strains
      clustered in several lineages of the dendrogram generated from the matrix of
      allelic mismatches between the different genotypes, a finding which does not
      support the hypothesis previously reported that the O139 serogroup is a unique
      clone. The statistical analysis performed in the V. cholerae O139 isolates
      suggested a clonal population structure. Moreover, the application of the
      Sawyer's test and split decomposition to detect intragenic recombination in the
      sequenced gene fragments did not indicate the existence of recombination in our
      O139 population.

PMID- 11844762
TI  - Trinucleotide GAA repeats dictate pMGA gene expression in Mycoplasma
      gallisepticum by affecting spacing between flanking regions.
AB  - The pMGA genes of the avian respiratory pathogen Mycoplasma gallisepticum encode
      a family of hemagglutinins that are subject to phase variation. A trinucleotide
      GAA repeat region is located upstream of the pMGA transcription start site. The
      length of the repeat region varies at a high frequency due to changes in the
      number of repeat units. Previous studies have shown that pMGA genes are
      transcribed when 12 GAA repeats are present but are not transcribed when the
      number of repeats is not 12. To further analyze the mechanism of gene regulation,
      the pMGA promoter region was modified either by deleting the nucleotides 5" of
      the GAA repeats or by inserting linkers of 10 or 12 bp at a position 3" of the
      repeats. The modified promoter region was fused to a promoterless lacZ gene and
      transformed into M. gallisepticum by using transposon Tn4001 as a vector.
      Transformants and successive generations of progeny were analyzed with 5-bromo-4
      chloro-3-indolyl-beta-D-galactopyranoside (X-Gal) to monitor beta-galactosidase
      activity. For the transformants of M. gallisepticum containing the reporter with
      deletion of nucleotides 5" of the GAA repeats, GAA-dependent pMGA gene regulation
      was abolished. For the transformants containing the reporter with an addition of
      10- or 12-bp linkers, lacZ was expressed only when eight GAA repeats were
      present. These data indicate that the nucleotides 5" of the GAA repeats as well
      as the spacing between the GAA repeats and sequences downstream (3") of the
      repeats are important for pMGA gene expression.

PMID- 11844761
TI  - YplA is exported by the Ysc, Ysa, and flagellar type III secretion systems of
      Yersinia enterocolitica.
AB  - Yersinia enterocolitica maintains three different pathways for type III protein
      secretion. Each pathway requires the activity of a specific multicomponent
      apparatus or type III secretion system (TTSS). Two of the TTSSs are categorized
      as contact-dependent systems which have been shown in a number of different
      symbiotic and pathogenic bacteria to influence interactions with host organisms
      by targeting effector proteins into the cytosol of eukaryotic cells. The third
      TTSS is required for the assembly of flagella and the secretion of the
      phospholipase YplA, which has been implicated in Y. enterocolitica virulence. In
      this study, YplA was expressed from a constitutive promoter in strains that
      contained only a single TTSS. It was determined that each of the three TTSSs is
      individually sufficient for YplA secretion. Environmental factors such as
      temperature, calcium availability, and sodium chloride concentration affected the
      contribution of each system to extracellular protein secretion and, under some
      conditions, more than one TTSS appeared to operate simultaneously. This suggests
      that some proteins might normally be exported by more than one TTSS in Y.
      enterocolitca.

PMID- 11844763
TI  - Two novel type III-secreted proteins of Xanthomonas campestris pv. vesicatoria
      are encoded within the hrp pathogenicity island.
AB  - The Hrp type III protein secretion system (TTSS) is essential for pathogenicity
      of gram-negative plant pathogen Xanthomonas campestris pv. vesicatoria. cDNA
      amplified fragment length polymorphism and reverse transcription-PCR analyses
      identified new genes, regulated by key hrp regulator HrpG, in the regions
      flanking the hrp gene cluster. Sequence analysis revealed genes encoding HpaG, a
      predicted leucine-rich repeat-containing protein, the lysozyme-like HpaH protein,
      and XopA and XopD, which are similar in sequence to Hpa1 from Xanthomonas oryzae
      pv. oryzae and PsvA from Pseudomonas syringae, respectively. XopA and XopD
      (Xanthomonas outer proteins) are secreted by the Xanthomonas Hrp TTSS and thus
      represent putative effector proteins. Mutations in xopA, but not in xopD,
      resulted in reduced bacterial growth in planta and delayed plant reactions in
      susceptible and resistant host plants. Since the xopD promoter contains a
      putative hrp box, which is characteristic of hrpL-regulated genes in P. syringae
      and Erwinia spp., the gene was probably acquired by horizontal gene transfer.
      Interestingly, the regions flanking the hrp gene cluster also contain insertion
      sequences and genes for a putative transposase and a tRNA(Arg). These features
      suggest that the hrp gene cluster of X. campestris pv. vesicatoria is part of a
      pathogenicity island.

PMID- 11844764
TI  - rRNA promoter activity in the fast-growing bacterium Vibrio natriegens.
AB  - The bacterium Vibrio natriegens can double with a generation time of less than 10
      min (R. G. Eagon, J. Bacteriol. 83:736-737, 1962), a growth rate that requires an
      extremely high rate of protein synthesis. We show here that V. natriegens' high
      potential for protein synthesis results from an increase in ribosome numbers with
      increasing growth rate, as has been found for other bacteria. We show that V.
      natriegens contains a large number of rRNA operons, and its rRNA promoters are
      extremely strong. The V. natriegens rRNA core promoters are at least as active in
      vitro as Escherichia coli rRNA core promoters with either E. coli RNA polymerase
      (RNAP) or V. natriegens RNAP, and they are activated by UP elements, as in E.
      coli. In addition, the E. coli transcription factor Fis activated V. natriegens
      rrn P1 promoters in vitro. We conclude that the high capacity for ribosome
      synthesis in V. natriegens results from a high capacity for rRNA transcription,
      and the high capacity for rRNA transcription results, at least in part, from the
      same factors that contribute most to high rates of rRNA transcription in E. coli,
      i.e., high gene dose and strong activation by UP elements and Fis.

PMID- 11844765
TI  - Positive growth rate-dependent regulation of the pdxA, ksgA, and pdxB genes of
      Escherichia coli K-12.
AB  - We found that transcription of the pdxA and pdxB genes, which mediate steps in
      the biosynthesis of the essential coenzyme pyridoxal 5"-phosphate, and the ksgA
      gene, which encodes an rRNA modification enzyme and is partly cotranscribed with
      pdxA, is subject to positive growth rate regulation in Escherichia coli K-12. The
      amounts of the pdxA-ksgA cotranscript and pdxB- and ksgA-specific transcripts and
      expression from pdxA- and pdxB-lacZ fusions increased as the growth rate
      increased. The half-lives of ksgA- and pdxB-specific transcripts were not
      affected by the growth rate, whereas the half-life of the pdxA-ksgA cotranscript
      was too short to be measured accurately. A method of normalization was applied to
      determine the amount of mRNA synthesized per gene and the rate of protein
      accumulation per gene. Normalization removed an apparent anomaly at fast growth
      rates and demonstrated that positive regulation of pdxB occurs at the level of
      transcription initiation over the whole range of growth rates tested. RNA
      polymerase limitation and autoregulation could not account for the positive
      growth rate regulation of pdxA, pdxB, and ksgA transcription. On the other hand,
      growth rate regulation of the amount of the pdxA-ksgA cotranscript was abolished
      by a fis mutation, suggesting a role for the Fis protein. In contrast, the fis
      mutation had no effect on pdxB- or ksgA-specific transcript amounts. The amounts
      of the pdxA-ksgA cotranscript and ksgA-specific transcript were repressed in the
      presence of high intracellular concentrations of guanosine tetraphosphate;
      however, this effect was independent of relA function for the pdxA-ksgA
      cotranscript. Amounts of the pdxB-specific transcript remained unchanged during
      amino acid starvation in wild-type and relA mutant strains.

PMID- 11844766
TI  - NorA functions as a multidrug efflux protein in both cytoplasmic membrane
      vesicles and reconstituted proteoliposomes.
AB  - Overexpression of NorA, an endogenous efflux transporter of Staphylococcus
      aureus, confers resistance to certain fluoroquinolone antimicrobials and diverse
      other substrates. The norA gene was amplified by PCR and cloned in the expression
      vector pTrcHis2. Histidine-tagged NorA (NorA-His) was overexpressed in
      Escherichia coli cells to prepare two experimental systems, everted membrane
      vesicles enriched with NorA-His and proteoliposomes reconstituted with purified
      NorA-His. In membrane vesicles, NorA-His actively transported Hoechst 33342, a
      dye that is strongly fluorescent in the membrane but has low fluorescence in an
      aqueous environment. Transport was activated by the addition of ATP or lactate
      and reversed by the addition of nigericin, with the addition of K(+)-valinomycin
      having little effect. Transport of Hoechst 33342 was inhibited competitively by
      verapamil, a known inhibitor of NorA, and by other NorA substrates, including
      tetraphenyl phosphonium and the fluoroquinolones norfloxacin and ciprofloxacin.
      In contrast, sparfloxacin, a fluoroquinolone whose antimicrobial activity is not
      affected by NorA expression, exhibited noncompetitive inhibition. NorA induction
      and overexpression yielded 0.5 to 1 mg of a largely homogeneous 40- to 43-kDa
      protein per liter of culture. NorA-His incorporated into proteoliposomes retained
      the ability to transport Hoechst 33342 in response to an artificial proton
      gradient, and transport was blocked by nigericin and verapamil. These data
      provide the first experimental evidence of NorA functioning as a self-sufficient
      multidrug transporter.

PMID- 11844767
TI  - Cel9M, a new family 9 cellulase of the Clostridium cellulolyticum cellulosome.
AB  - A new cellulosomal protein from Clostridium cellulolyticum Cel9M was
      characterized. The protein contains a catalytic domain belonging to family 9 and
      a dockerin domain. Cel9M is active on carboxymethyl cellulose, and the hydrolysis
      of this substrate is accompanied by a decrease in viscosity. Cel9M has a slight,
      albeit significant, activity on both Avicel and bacterial microcrystalline
      cellulose, and the main soluble sugar released is cellotetraose. Saccharification
      of bacterial microcrystalline cellulose by Cel9M in association with two other
      family 9 enzymes from C. cellulolyticum, namely, Cel9E and Cel9G, was measured,
      and it was found that Cel9M acts synergistically with Cel9E. Complexation of
      Cel9M with the mini-CipC1 containing the cellulose binding domain, the X2 domain,
      and the first cohesin domain of the scaffoldin CipC of the bacterium did not
      significantly increase the hydrolysis of Avicel and bacterial microcrystalline
      cellulose.

PMID- 11844768
TI  - Gamma integrase complementation at the level of DNA binding and complex
      formation.
AB  - Site-specific recombinases of the gamma Int family carry out two single-strand
      exchanges by binding as head-to-head dimers on inverted core-type DNA sites. Each
      protomer may cleave its own site as a monomer in cis (as for Cre recombinase), or
      it may recruit the tyrosine from its partner in trans to form a composite active
      site (as for Flp recombinase). The crystal structure of the gamma Int catalytic
      domain is compatible with both cleavage mechanisms, but two previous biochemical
      studies on gamma integrase (Int) generated data that were not in agreement.
      Support for cis and trans cleavage came from assays with bispecific DNA
      substrates for gamma and HK022 Ints and from functional complementation between
      recombination-deficient mutants, respectively. The data presented here do not
      provide new evidence for cis cleavage, but they strongly suggest that the
      previously described complementation results cannot be used in support of a trans
      cleavage mechanism. We show here that IntR212Q retains some residual catalytic
      function but is impaired in binding to core-type DNA on linear substrates and in
      forming higher-order attL intasome structures. The binding-proficient mutant
      IntY342F can stabilize IntR212Q binding to core-type DNA through protein-protein
      interactions. Similarly, the formation of higher-order Int complexes with arm-
      and core-type DNA is boosted with both mutants present. This complementation
      precedes cleavage and thus precludes any conclusions about the mechanism of
      catalysis. Cross-core stimulation of wild-type HK022-Int cleavage on its cognate
      site (in cis) by mutant gamma Ints on bispecific core DNA suicide substrates is
      shown to be independent of the catalytic tyrosine but appears to be proportional
      to the respective core-binding affinities of the gamma Int mutants.

PMID- 11844769
TI  - Effects of a squalene epoxidase inhibitor, terbinafine, on ether lipid
      biosyntheses in a thermoacidophilic archaeon, Thermoplasma acidophilum.
AB  - The archaeal plasma membrane consists mainly of diether lipids and tetraether
      lipids instead of the usual ester lipids found in other organisms. Although a
      molecule of tetraether lipid is thought to be synthesized from two molecules of
      diether lipids, there is no direct information about the biosynthetic pathway(s)
      or intermediates of tetraether lipid biosynthesis. In this study, we examined the
      effects of the fungal squalene epoxidase inhibitor terbinafine on the growth and
      ether lipid biosyntheses in the thermoacidophilic archaeon Thermoplasma
      acidophilum. Terbinafine was found to inhibit the growth of T. acidophilum in a
      concentration-dependent manner. When growing T. acidophilum cells were pulse
      labeled with [2-(14)C]mevalonic acid in the presence of terbinafine,
      incorporation of radioactivity into the tetraether lipid fraction was strongly
      suppressed, while accumulation of radioactivity was noted at the position
      corresponding to diether lipids, depending on the concentration of terbinafine.
      After the cells were washed with fresh medium and incubated further without the
      radiolabeled substrate and the inhibitor, the accumulated radioactivity in the
      diether lipid fraction decreased quickly while that in the tetraether lipids
      increased simultaneously, without significant changes in the total radioactivity
      of ether lipids. These results strongly suggest that terbinafine inhibits the
      biosynthesis of tetraether lipids from a diether-type precursor lipid(s). The
      terbinafine treatment will be a tool for dissecting tetraether lipid biosynthesis
      in T. acidophilum.

PMID- 11844770
TI  - Quantitative assessment of oxygen availability: perceived aerobiosis and its
      effect on flux distribution in the respiratory chain of Escherichia coli.
AB  - Despite a large number of studies on the role of oxygen in cellular processes,
      there is no consensus as to how oxygen availability to the cell should be
      defined, let alone how it should be quantified. Here, a quantitative definition
      for oxygen availability (perceived aerobiosis) is presented; the definition is
      based on a calibration with reference to the minimal oxygen supply rate needed
      for fully oxidative catabolism (i.e., complete conversion of the energy source to
      CO(2) and water for glucose-limited conditions). This quantitative method is used
      to show how steady-state electron fluxes through the alternative cytochrome
      oxidases of Escherichia coli are distributed as a function of the extent of
      aerobiosis of glucose-limited chemostat cultures. At low oxygen availability the
      electron flux is mainly via the high-affinity cytochrome bd oxidase, and, at
      higher oxygen availability, a similar phenomenon occurs but now via the low
      affinity cytochrome bo oxidase. The main finding is that the catabolic activities
      of E. coli (and specifically its respiratory activity) are affected by the actual
      oxygen availability per unit of biomass rather than by the residual dissolved
      oxygen concentration of the culture.

PMID- 11844771
TI  - Posttranscriptional activation of the transcriptional activator Rob by dipyridyl
      in Escherichia coli.
AB  - The transcriptional activator Rob consists of an N-terminal domain (NTD) of 120
      amino acids responsible for DNA binding and promoter activation and a C-terminal
      domain (CTD) of 169 amino acids of unknown function. Although several thousand
      molecules of Rob are normally present per Escherichia coli cell, they activate
      promoters of the rob regulon poorly. We report here that in cells treated with
      either 2,2"- or 4,4"-dipyridyl (the latter is not a metal chelator), Rob-mediated
      transcription of various rob regulon promoters was increased substantially. A
      small, growth-phase-dependent effect of dipyridyl on the rob promoter was
      observed. However, dipyridyl enhanced Rob's activity even when rob was regulated
      by a heterologous (lac) promoter showing that the action of dipyridyl is mainly
      posttranscriptional. Mutants lacking from 30 to 166 of the C-terminal amino acids
      of Rob had basal levels of activity similar to that of wild-type cells, but
      dipyridyl treatment did not enhance this activity. Thus, the CTD is not an
      inhibitor of Rob but is required for activation of Rob by dipyridyl. In contrast
      to its relatively low activity in vivo, Rob binding to cognate DNA and activation
      of transcription in vitro is similar to that of MarA, which has a homologous NTD
      but no CTD. In vitro nuclear magnetic resonance studies demonstrated that 2,2"
      dipyridyl binds to Rob but not to the CTD-truncated Rob or to MarA, suggesting
      that the effect of dipyridyl on Rob is direct. Thus, it appears that Rob can be
      converted from a low activity state to a high-activity state by a CTD-mediated
      mechanism in vivo or by purification in vitro.

PMID- 11844772
TI  - Disruption of lolCDE, encoding an ATP-binding cassette transporter, is lethal for
      Escherichia coli and prevents release of lipoproteins from the inner membrane.
AB  - ATP-binding cassette transporter LolCDE was previously identified, by using
      reconstituted proteoliposomes, as an apparatus catalyzing the release of outer
      membrane-specific lipoproteins from the inner membrane of Escherichia coli.
      Mutations resulting in defective LolD were previously shown to be lethal for E.
      coli. The amino acid sequences of LolC and LolE are similar to each other, but
      the necessity of both proteins for lipoprotein release has not been proved.
      Moreover, previous reconstitution experiments did not clarify whether or not
      LolCDE is the sole apparatus for lipoprotein release. To address these issues, a
      chromosomal lolC-lolD-lolE null mutant harboring a helper plasmid that carries
      the lolCDE genes and a temperature-sensitive replicon was constructed. The mutant
      failed to grow at a nonpermissive temperature because of the depletion of LolCDE.
      In addition to functional LolD, both LolC and LolE were required for growth. At a
      nonpermissive temperature, the outer membrane lipoproteins were mislocalized in
      the inner membrane since LolCDE depletion inhibited the release of lipoproteins
      from the inner membrane. Furthermore, both LolC and LolE were essential for the
      release of lipoproteins. On the other hand, LolCDE depletion did not affect the
      translocation of a lipoprotein precursor across the inner membrane and subsequent
      processing to the mature lipoprotein. From these results, we conclude that the
      LolCDE complex is an essential ABC transporter for E. coli and the sole apparatus
      mediating the release of outer membrane lipoproteins from the inner membrane.

PMID- 11844773
TI  - Mutations in the thiol-disulfide oxidoreductases BdbC and BdbD can suppress
      cytochrome c deficiency of CcdA-defective Bacillus subtilis cells.
AB  - Cytochromes of the c type in the gram-positive bacterium Bacillus subtilis are
      all membrane anchored, with their heme domains exposed on the outer side of the
      cytoplasmic membrane. They are distinguished from other cytochromes by having
      heme covalently attached by two thioether bonds. The cysteinyls in the heme
      binding site (CXXCH) in apocytochrome c must be reduced in order for the covalent
      attachment of the heme to occur. It has been proposed that CcdA, a membrane
      protein, transfers reducing equivalents from thioredoxin in the cytoplasm to
      proteins on the outer side of the cytoplasmic membrane. Strains deficient in the
      CcdA protein are defective in cytochrome c and spore synthesis. We have
      discovered that mutations in the bdbC and bdbD genes can suppress the defects
      caused by lack of CcdA. BdbC and BdbD are thiol-disulfide oxidoreductases. Our
      experimental findings indicate that these B. subtilis proteins functionally
      correspond to the well-characterized Escherichia coli DsbB and DsbA proteins,
      which catalyze the formation of disulfide bonds in proteins in the periplasmic
      space.

PMID- 11844774
TI  - In vitro serial passage of Staphylococcus aureus: changes in physiology,
      virulence factor production, and agr nucleotide sequence.
AB  - Recently, we observed that Staphylococcus aureus strains newly isolated from
      patients had twofold-higher aconitase activity than a strain passaged extensively
      in vitro, leading us to hypothesize that aconitase specific activity decreases
      over time during in vitro passage. To test this hypothesis, a strain recovered
      from a patient with toxic shock syndrome was serially passaged for 6 weeks, and
      the aconitase activity was measured. Aconitase specific activity decreased 38% (P
      < 0.001) by the sixth week in culture. During serial passage, S. aureus existed
      as a heterogeneous population with two colony types that had pronounced (wild
      type) or negligible zones of beta-hemolytic activity. The cell density-sensing
      accessory gene regulatory (agr) system regulates beta-hemolytic activity.
      Surprisingly, the percentage of colonies with a wild-type beta-hemolytic
      phenotype correlated strongly with aconitase specific activity (rho = 0.96),
      suggesting a common cause of the decreased aconitase specific activity and the
      variation in percentage of beta-hemolytic colonies. The loss of the beta
      hemolytic phenotype also coincided with the occurrence of mutations in the agrC
      coding region or the intergenic region between agrC and agrA in the derivative
      strains. Our results demonstrate that in vitro growth is sufficient to result in
      mutations within the agr operon. Additionally, our results demonstrate that S.
      aureus undergoes significant phenotypic and genotypic changes during serial
      passage and suggest that vigilance should be used when extrapolating data
      obtained from the study of high-passage strains.

PMID- 11844775
TI  - Conserved low-affinity nickel-binding amino acids are essential for the function
      of the nickel permease NixA of Helicobacter pylori.
AB  - Nickel acquisition is necessary for urease activity, a major virulence factor of
      the human gastric pathogen Helicobacter pylori. The nickel permease NixA of H.
      pylori is a member of the single-component nickel-cobalt transporter family. To
      identify functionally relevant amino acids of NixA, single-site exchanges were
      introduced into NixA via PCR-based mutagenesis. This study investigated one of
      the recognition motifs for this family in transmembrane segment III and other
      conserved amino acids, mostly with possible nickel-binding capacities. The mutant
      alleles were expressed in Escherichia coli, and activity of the altered permeases
      was analyzed by measuring nickel accumulation and urease activity. Expression was
      checked by immunoblotting after sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis with a NixA-specific antibody. Replacement of Phe-75 and His-79
      both part of the characteristic sequence motif-and of Asn-127, Thr-195, and Ser
      197 with alanine abolished nickel uptake in the E. coli system. The results were
      unchanged if these amino acids were replaced with residues more similar to the
      original amino acid. The phenotype of the null mutants was independent of the
      culture medium. Mutation of Val-82, Tyr-242, Thr-260, His-181, and His-15
      strongly affected uptake activity under nickel limitation on complex Luria
      Bertani medium but had little effect in minimal medium. Eight other conserved
      amino acids (Ser-80, Ser-81, Phe-119, Trp-180, Tyr-183, Trp-244, Pro-249, and Asn
      256) were found to be dispensable for the function of NixA. These results show
      that atypical nickel-binding amino acids play an important function in nickel
      uptake and that most of the essential amino acids are clustered in conserved
      motifs.

PMID- 11844776
TI  - Charged amino acids conserved in the aromatic acid/H+ symporter family of
      permeases are required for 4-hydroxybenzoate transport by PcaK from Pseudomonas
      putida.
AB  - Charged amino acids in the predicted transmembrane portion of PcaK, a permease
      from Pseudomonas putida that transports 4-hydroxybenzoate (4-HBA), were required
      for 4-HBA transport, and they were also required for P. putida to have a
      chemotactic response to 4-HBA. An essential amino acid motif (DGXD) containing
      aspartate residues is located in the first transmembrane segment of PcaK and is
      conserved in the aromatic acid/H+ symporter family of the major facilitator
      superfamily of transporters.

PMID- 11844777
TI  - Directed mutagenesis and plasmid-based complementation in the methanogenic
      archaeon Methanosarcina acetivorans C2A demonstrated by genetic analysis of
      proline biosynthesis.
AB  - We report here the first use of directed mutagenesis in Methanosarcina
      acetivorans C2A. The method employs homologous recombination-mediated gene
      replacement and was used to construct a variety of proline auxotrophs with
      mutations in the proABC locus. Each mutation was also complemented in trans with
      autonomously replicating Methanosarcina-Escherichia plasmid shuttle vectors.

PMID- 11844778
TI  - Bypass of A- and B-signaling requirements for Myxococcus xanthus development by
      mutations in spdR.
AB  - Mutations in spdR, previously reported to bypass the developmental requirement
      for B-signaling in Myxococcus xanthus, also bypass the requirement for A
      signaling but not C-, D-, or E-signaling. Mutations in spdR restored nearly wild
      type levels of sporulation to representative A-signal-deficient mutants carrying
      asgA476, asgB480, and asgC767 and improved the quality of fruiting body formation
      in the asgB480 mutant. The defect in A-factor production by the asgB480 mutant
      was not restored in the spdR2134 asgB480 double mutant.

PMID- 11844779
TI  - Glucose-resistant sporulation in Bacillus subtilis crsA47 mutants does not depend
      on promoter switching at the spo0A gene.
AB  - We have found that sporulation in Bacillus subtilis crsA47 mutants does not
      require the sigma(H)-dependent promoter of the spo0A gene. This implies that the
      glucose-resistant sporulation phenotype of this strain is not related to the
      switch from the vegetative-stage sigma(A)-dependent promoter to the sigma(H)
      dependent promoter at the spo0A gene.

PMID- 11844780
TI  - Mapping of Myxococcus xanthus social motility dsp mutations to the dif genes.
AB  - Myxococcus xanthus dsp and dif mutants have similar phenotypes in that they are
      deficient in social motility and fruiting body development. We compared the two
      loci by genetic mapping, complementation with a cosmid clone, DNA sequencing, and
      gene disruption and found that 16 of the 18 dsp alleles map to the dif genes.
      Another dsp allele contains a mutation in the sglK gene. About 36.6 kb around the
      dsp-dif locus was sequenced and annotated, and 50% of the genes are novel.

PMID- 11844781
TI  - Monitoring key reactions in degradation of chloroaromatics by in situ (1)H
      nuclear magnetic resonance: solution structures of metabolites formed from cis
      dienelactone.
AB  - A (1)H nuclear magnetic resonance ((1)H NMR) assay was used to study the
      enzymatic transformation of cis-dienelactone, a central intermediate in the
      degradation of chloroaromatics. It was shown that the product of the cis
      dienelactone hydrolase reaction is maleylacetate, in which there is no evidence
      for the formation of 3-hydroxymuconate. Under acidic conditions, the product
      structure was 4-carboxymethyl-4-hydroxybut-2-en-4-olide. Maleylacetate was
      transformed by maleylacetate reductase into 3-oxoadipate, a reaction competing
      with spontaneous decarboxylation into cis-acetylacrylate. One-dimensional (1)H
      NMR in (1)H(2)O could thus be shown to be an excellent noninvasive tool for
      monitoring enzyme activities and assessing the solution structure of substrates
      and products.

PMID- 11844782
TI  - New class of IMP cyclohydrolases in Methanococcus jannaschii.
AB  - The enzyme responsible for observed IMP cyclohydrolase activity in Methanococcus
      jannaschii was purified and sequenced: its genetic locus was found to correspond
      to gene MJ0626. The MJ0626 gene was cloned, and its protein product was expressed
      in Escherichia coli and shown to catalyze the cyclization of 5
      formylamidoimidazole-4-carboxamide ribonucleotide to IMP. The enzyme has no
      sequence similarity to known enzymes, and its catalytic properties appear
      distinct from any characterized IMP cyclohydrolase. The purO gene for the enzyme
      is currently found only in the domain Archaea.

PMID- 11844784
TI  - Novel group I intron in the tRNA(Leu)(UAA) gene of a gamma-proteobacterium
      isolated from a deep subsurface environment.
AB  - A group I intron has been found to interrupt the anticodon loop of the
      tRNA(Leu)(UAA) gene in a bacterium belonging to the gamma-subdivision of
      Proteobacteria and isolated from a deep subsurface environment. The subsurface
      isolate SMCC D0715 was identified as belonging to the genus Pseudomonas. The
      group I intron from this isolate is the first to be reported for gamma
      proteobacteria, and the first instance of a tRNA(Leu)(UAA) group I intron to be
      found in a group of bacteria other than cyanobacteria. The 231-nucleotide (nt)
      intron's sequence has group I conserved elements and folds into a bona fide group
      I secondary structure with canonical base-paired segments P1 to P9 and a paired
      region, P10. The D0715 intron possesses the 11-nt motif CCUACG. UAUGG in its P8
      region, a feature not common in bacterial introns. To date, phylogenetic analysis
      has shown that bacterial introns form two distinct families, and their complex
      distribution suggests that both lateral transfer and common ancestry have taken
      part in the evolutionary history of these elements.

PMID- 11844783
TI  - The flavoenzyme ferredoxin (flavodoxin)-NADP(H) reductase modulates NADP(H)
      homeostasis during the soxRS response of Escherichia coli.
AB  - Escherichia coli cells from strain fpr, deficient in the soxRS-induced ferredoxin
      (flavodoxin)-NADP(H) reductase (FPR), display abnormal sensitivity to the
      bactericidal effects of the superoxide-generating reagent methyl viologen (MV).
      Neither bacteriostatic effects nor inactivation of oxidant-sensitive hydrolyases
      could be detected in fpr cells exposed to MV. FPR inactivation did not affect the
      MV-driven soxRS response, whereas FPR overexpression led to enhanced stimulation
      of the regulon, with concomitant oxidation of the NADPH pool. Accumulation of a
      site-directed FPR mutant that uses NAD(H) instead of NADP(H) had no effect on
      soxRS induction and failed to protect fpr cells from MV toxicity, suggesting that
      FPR contributes to NADP(H) homeostasis in stressed bacteria.

PMID- 11844785
TI  - AmfS, an extracellular peptidic morphogen in Streptomyces griseus.
AB  - The amf gene cluster was previously identified as a regulator for the onset of
      aerial-mycelium formation in Streptomyces griseus. The nucleotide sequences of
      amf and its counterparts in other species revealed a conserved gene organization
      consisting of five open reading frames. A nonsense mutation in amfS, encoding a
      43-amino-acid peptide, caused significant blocking of aerial-mycelium formation
      and streptomycin production, suggesting its role as a regulatory molecule.
      Extracellular-complementation tests for the aerial-mycelium-deficient phenotype
      of the amfS mutant demonstrated that AmfS was secreted by the wild-type strain. A
      null mutation in amfBA, encoding HlyB-like membrane translocators, abolished the
      extracellular AmfS activity without affecting the wild-type morphology, which
      suggests that AmfBA is involved not in production but in export of AmfS. A
      synthetic C-terminal octapeptide partially induced aerial-mycelium formation in
      the amfS mutant, which suggests that an AmfS derivative, but not AmfS itself,
      serves as an extracellular morphogen.

PMID- 11844786
TI  - Transcription of the SsrAB regulon is repressed by alkaline pH and is independent
      of PhoPQ and magnesium concentration.
AB  - The Salmonella pathogenicity island 2 (SPI-2) type III secretion system is
      expressed by intracellular bacteria and translocates effector proteins across the
      vacuolar membrane. Signals sensed by Salmonella enterica serovar Typhimurium in
      the intracellular compartment activate SPI-2 gene expression through the two
      component regulatory system SsrAB. The effects of environmental and genetic
      signals on expression of the SsrAB-regulated gene sspH2 were examined. SsrAB
      dependent activation of sspH2 was detected in the presence of both low and
      moderate concentrations of magnesium or calcium and at acidic and neutral pHs.
      The levels of expression were comparable to those detected in bacteria recovered
      from cultured macrophages. The induction in media at alkaline pHs (pH 7.5 and
      8.0) was greatly reduced compared to the induction observed at pH 7.0 or at a
      lower pH, suggesting that alkaline pH represses SsrAB activation. In addition,
      the PhoPQ two-component system, which is also activated intracellularly, was not
      required for activation of SsrAB.

PMID- 11844787
TI  - Characterization of the petI and res operons of Acidithiobacillus ferrooxidans.
AB  - DNA sequence analysis and bioinformatic interpretations have identified two
      adjacent clusters of genes potentially involved in the formation of a bc1 complex
      and in the maturation of a cytochrome c-type protein in two strains (ATCC 19859
      and ATCC 33020) of the acidophilic, chemolithoautotrophic bacterium
      Acidithiobacillus ferrooxidans (formerly Thiobacillus ferrooxidans). Reverse
      transcriptase-PCR experiments suggest that the two clusters are organized as
      operons, and +1 start sites of transcription for the operons have been determined
      by primer extension experiments. Potential promoters have been identified. The
      presence of these operons lends support to a recent model of reverse electron
      flow and is consistent with previous reports of phenotypic switching in this
      bacterium.

PMID- 11844788
TI  - Divergent regulation of the growth-promoting gene IEX-1 by the p53 tumor
      suppressor and Sp1.
AB  - IEX-1, a recently discovered early response gene, regulates cell growth and
      apoptosis. IEX-1 gene expression is regulated by a variety of factors such as x
      irradiation, ultraviolet radiation, steroids, growth factors, and inflammatory
      stimuli. By systematic examination of the IEX-1 promoter, we show that IEX-1 gene
      expression is controlled by multiple conserved gene regulatory elements and that
      IEX-1 is a downstream target of the p53 tumor suppressor and Sp1. In addition,
      p300, Sox, nuclear factor-kappaB, and AP4 appear to be modulators of IEX-1 gene
      expression to a lesser degree. We found that there is at least one Sp1 element
      that functions as an activator and contributes to high basal transcriptional
      levels of the IEX-1 gene. We demonstrate the presence of a p53 response element
      that represses IEX-1 promoter activity in HaCaT keratinocytes, indicating that
      Sp1 and p53 have opposite effects on IEX-1 gene expression. We conclude that IEX
      1 expression in cells is regulated by the p53 tumor suppressor and Sp1, thus
      providing a direct mechanism for control of cell proliferation.

PMID- 11844790
TI  - Modulation of estrogen receptor-mediated transactivation by orphan receptor TR4
      in MCF-7 cells.
AB  - The human testicular orphan receptor 4 (TR4) is a member of the nuclear receptor
      superfamily that shows a broad tissue distribution with higher expression in the
      nervous system and male reproductive tract. TR4 functions as a transcriptional
      modulator that controls various target genes via binding to the DNA hormone
      response elements. Here we report that instead of direct binding to hormone
      response elements for gene regulation, TR4 can also go through direct protein
      protein interaction to repress estrogen receptor (ER)-mediated transactivation.
      Electrophoretic mobility shift and glutathione S-transferase pull-down assays
      clearly demonstrate that the direct interaction between TR4 and ER will inhibit
      the homodimerization of ER and interrupt/prevent ER binding to the estrogen
      response element. The consequence of these events may then result in the
      suppression of ER target genes, such as cyclin D1 and pS2 and inhibition of ER
      mediated cell proliferation in the MCF-7 cells stably transfected with TR4.
      Together, our results showing that TR4 can suppress ER function via protein
      protein interaction not only represent a unique cross-talk signaling pathway in
      the nuclear receptor superfamily, it may also provide us with a new strategy to
      modulate ER function in the breast cancer cells.

PMID- 11844789
TI  - Rac1 and Cdc42 but not RhoA or Rho kinase activities are required for neurite
      outgrowth induced by the Netrin-1 receptor DCC (deleted in colorectal cancer) in
      N1E-115 neuroblastoma cells.
AB  - Netrins are chemotropic guidance cues that attract or repel growing axons during
      development. DCC (deleted in colorectal cancer), a transmembrane protein that is
      a receptor for netrin-1, is implicated in mediating both responses. However, the
      mechanism by which this is achieved remains unclear. Here we report that Rho
      GTPases are required for embryonic spinal commissural axon outgrowth induced by
      netrin-1. Using N1E-115 neuroblastoma cells, we found that both Rac1 and Cdc42
      activities are required for DCC-induced neurite outgrowth. In contrast, down
      regulation of RhoA and its effector Rho kinase stimulates the ability of DCC to
      induce neurite outgrowth. In Swiss 3T3 fibroblasts, DCC was found to trigger
      actin reorganization through activation of Rac1 but not Cdc42 or RhoA. We
      detected that stimulation of DCC receptors with netrin-1 resulted in a 4-fold
      increase in Rac1 activation. These results implicate the small GTPases Rac1,
      Cdc42, and RhoA as essential components that participate in signaling the
      response of axons to netrin-1 during neural development.

PMID- 11844791
TI  - Serotonin transporter function and pharmacology are sensitive to expression
      level: evidence for an endogenous regulatory factor.
AB  - We express mammalian serotonin transporters (SERTs) in Xenopus oocytes by cRNA
      injection and measure 5-hydroxytryptamine (5-HT) transport and 5-HT-induced
      current at varying expression levels. Transport and current both increase
      sigmoidally with the amount of cRNA injected, but current requires approximately
      5-fold more cRNA to elicit a half-maximal response. Western blots of SERT protein
      demonstrate that current, but not transport, correlates linearly with the amount
      of SERT on the plasma membrane. In oocytes co-injected with wild-type SERT and an
      inactive SERT mutant, transport is similar to SERT alone, but current is
      attenuated. The charge/transport ratio reports the differential sensitivity of
      transport and current to increasing SERT cRNA injection and mutant co-expression.
      Manipulations that alter the charge/transport ratio also perturb substrate and
      inhibitor recognition. 5-HT, d-amphetamine, cocaine, and paroxetine inhibit
      transport more potently at lower expression levels; however, 5-HT potency for
      induction of current is similar at high and low expression. Moreover, the
      apparent potency of cRNA for transport depends on 5-HT concentration. We
      postulate that SERT interacts allosterically with an endogenous factor of limited
      abundance to alter substrate and inhibitor potency and the balance of 5-HT
      transport and channel-like activity.

PMID- 11844792
TI  - The slippage of the Ca2+ pump and its control by anions and curcumin in skeletal
      and cardiac sarcoplasmic reticulum.
AB  - Ca(2+) transport by sarcoplasmic reticulum (SR) ATPase occurs with an optimal
      coupling ratio of 2 Ca(2+) per ATP in pre-steady state. However, slippage of the
      pump and lower coupling ratios are observed in steady state. Slippage depends on
      the presence of high Ca(2+) in the lumen of SR vesicles and high nucleotide in
      the medium. Thereby, Ca(2+) and/or nucleotide-bound phosphoenzyme intermediates
      accumulate and undergo uncoupled cleavage, before vectorial translocation of
      bound Ca(2+) in the forward direction of the cycle or before productive reversal
      to ATP synthesis. Transport efficiency and coupling ratios are improved by
      reduction of nucleotide concentration in the presence of ATP regenerating systems
      and/or complexation of luminal Ca(2+) with phosphate or oxalate. Curcumin (1-5
      microm) lowers the concentration of phosphate or oxalate required to reduce
      slippage of the Ca(2+) pump. Thereby, under appropriate conditions, curcumin
      favors kinetic flow, completion of productive cycles, and improvement of coupling
      ratios. The findings obtained with isolated SR vesicles suggest that slippage is
      an important phenomenon under prevailing conditions of muscle fibers in situ.
      Ca(2+) transport and its slippage can be improved by curcumin in cardiac as well
      as in skeletal SR, raising the possibility of pharmacological interventions to
      correct defective Ca(2+) homeostasis. Higher curcumin concentrations (5-30
      microm), however, inhibit overall ATPase activity and Ca(2+) transport by
      interfering with phosphoenzyme formation with ATP or P(i).

PMID- 11844793
TI  - Slow-tight binding inhibition of xylanase by an aspartic protease inhibitor:
      kinetic parameters and conformational changes that determine the affinity and
      selectivity of the bifunctional nature of the inhibitor.
AB  - The first report of slow-tight inhibition of xylanase by a bifunctional inhibitor
      alkalo-thermophilic Bacillus inhibitor (ATBI), from an extremophilic Bacillus sp.
      is described. ATBI inhibits aspartic protease (Dash, C., and Rao, M. (2001) J.
      Biol. Chem., 276, 2487-2493) and xylanase (Xyl I) from a Thermomonospora sp. The
      steady-state kinetics revealed time-dependent competitive inhibition of Xyl I by
      ATBI, consistent with two-step inhibition mechanism. The inhibition followed a
      rapid equilibrium step to form a reversible enzyme-inhibitor complex (EI), which
      isomerizes to the second enzyme-inhibitor complex (EI*), which dissociated at a
      very slow rate. The rate constants determined for the isomerization of EI to EI*,
      and the dissociation of EI* were 13 +/- 1 x 10(-6) s(-1) and 5 +/- 0.5 x 10(-8)
      s(-1), respectively. The K(i) value for the formation of EI complex was 2.5 +/-
      0.5 microm, whereas the overall inhibition constant K(i)* was 7 +/- 1 nm. The
      conformational changes induced in Xyl I by ATBI were monitored by fluorescence
      spectroscopy and the rate constants derived were in agreement with the kinetic
      data. Thus, the conformational alterations were correlated to the isomerization
      of EI to EI*. ATBI binds to the active site of the enzyme and disturbs the native
      interaction between the histidine and lysine, as demonstrated by the abolished
      isoindole fluorescence of o-phthalaldehyde (OPTA)-labeled Xyl I. Our results
      revealed that the inactivation of Xyl I is due to the disruption of the hydrogen
      bonding network between the essential histidine and other residues involved in
      catalysis and a model depicting the probable interaction between ATBI or OPTA
      with Xyl I has been proposed.

PMID- 11844794
TI  - Physical interaction of p73 with c-Myc and MM1, a c-Myc-binding protein, and
      modulation of the p73 function.
AB  - p73 shares high sequence homology with the tumor suppressor p53. Like p53,
      ectopic overexpression of p73 induces cell cycle arrest and/or apoptosis, and
      these biological activities are linked to its sequence-specific transactivation
      function. The COOH-terminal region of p73 is unique and has a function to
      modulate DNA-binding ability and transactivation activity. To identify and
      characterize cellular proteins that interact with the COOH-terminal region of p73
      alpha and regulate its activity, we employed a yeast-based two-hybrid screen with
      a human fetal brain cDNA library. We found MM1, a nuclear c-Myc-binding protein,
      was associated with p73 alpha in both yeast two-hybrid and in vitro pull-down
      assays. In mammalian cells, MM1 co-immunoprecipitated with p73 alpha, whereas p73
      beta and tumor suppressor p53 did not interact with MM1. Overexpression of MM1 in
      p53-deficient osteosarcoma SAOS-2 cells enhanced the p73 alpha-dependent
      transcription from the p53/p73-responsive Bax and PG13 promoters, whereas p73
      beta- and p53-mediated transcriptional activation was unaffected in the presence
      of MM1. MM1 also stimulated the p73 alpha-mediated growth suppression in SAOS-2
      cells. More importantly, we found that c-Myc was physically associated with p73
      alpha and significantly impaired the transcriptional activity of p73 alpha on Bax
      and p21(waf1) promoters. Expression of MM1 strongly reduced the c-Myc-mediated
      inhibitory activity on p73 alpha. These results suggest that MM1 may act as a
      molecular partner for p73 to prevent the c-Myc-mediated inhibitory effect on its
      activity.

PMID- 11844795
TI  - Lipid rafts orchestrate signaling by the platelet receptor glycoprotein VI.
AB  - The platelet collagen receptor glycoprotein VI (GPVI) couples to the immune
      receptor adaptor Fc receptor gamma-chain (FcRgamma) and signals using many of the
      same intracellular signaling molecules as immune receptors. Studies of immune
      receptor signaling have revealed a critical role for specialized areas of the
      cell membrane known as lipid rafts, which are enriched in essential signaling
      molecules. However, the role of lipid rafts in signaling in nonimmune cells such
      as platelets remains poorly defined. This study shows that GPVI-FcRgamma does not
      constitutively associate with rafts, but is recruited to lipid rafts following
      receptor stimulation in both GPVI-expressing RBL-2H3 cells and human platelets.
      FcRgamma is required for GPVI association with lipid rafts, as mutant GPVI
      receptors that do not couple to FcRgamma were unable to associate with lipid
      rafts after receptor clustering. Following GPVI stimulation in platelets,
      virtually all phosphorylated FcRgamma was found in lipid rafts, but inhibition of
      FcRgamma phosphorylation did not block receptor association with lipid rafts.
      This work demonstrates that lipid rafts orchestrate GPVI receptor signaling in
      platelets in a manner analogous to immune cell receptors and supports a model of
      GPVI signaling in which FcRgamma phosphorylation is controlled by ligand
      dependent association with lipid rafts.

PMID- 11844797
TI  - Arachidonic acid promotes phosphorylation of 5-lipoxygenase at Ser-271 by MAPK
      activated protein kinase 2 (MK2).
AB  - We demonstrated previously that 5-lipoxygenase (5-LO), a key enzyme in
      leukotriene biosynthesis, can be phosphorylated by p38 MAPK-regulated MAPKAP
      kinases (MKs). Here we show that mutation of Ser-271 to Ala in 5-LO abolished MK2
      catalyzed phosphorylation and clearly reduced phosphorylation by kinases prepared
      from stimulated polymorphonuclear leukocytes and Mono Mac 6 cells. Compared with
      heat shock protein 27 (Hsp-27), 5-LO was a weak substrate for MK2. However, the
      addition of unsaturated fatty acids (i.e. arachidonate 1-50 microm) up-regulated
      phosphorylation of 5-LO, but not of Hsp-27, by active MK2 in vitro, resulting in
      a similar phosphorylation as for Hsp-27. 5-LO was phosphorylated also by other
      serine/threonine kinases recognizing the motif Arg-Xaa-Xaa-Ser (protein kinase A,
      Ca(2+)/calmodulin-dependent kinase II), but these activities were not increased
      by fatty acids. HeLa cells expressing wild type 5-LO or S271A-5-LO, showed
      prominent 5-LO activity when incubated with Ca(2+)-ionophore plus arachidonate.
      However, when stimulated with only exogenous arachidonic acid, activity for the
      S271A mutant was significantly lower as compared with wild type 5-LO. It appears
      that phosphorylation at Ser-271 is more important for 5-LO activity induced by a
      stimulus that does not prominently increase intracellular Ca(2+) and that
      arachidonic acid stimulates leukotriene biosynthesis also by promoting this MK2
      catalyzed phosphorylation.

PMID- 11844798
TI  - A cross-linked profilin-actin heterodimer interferes with elongation at the fast
      growing end of F-actin.
AB  - Profilin and beta/gamma-actin from calf thymus were covalently linked using the
      zero-length cross-linker 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide in
      combination with N-hydroxysuccinimide, yielding a single product with an apparent
      molecular mass of 60 kDa. Sequence analysis and x-ray crystallographic
      investigations showed that the cross-linked residues were glutamic acid 82 of
      profilin and lysine 113 of actin. The cross-linked complex was shown to bind with
      high affinity to deoxyribonuclease I and poly(l-proline). It also bound and
      exchanged ATP with kinetics close to that of unmodified profilin-actin and
      inhibited the intrinsic ATPase activity of actin. This inhibition occurred even
      in conditions where actin normally forms filaments. By these criteria the cross
      linked profilin-actin complex retains the characteristics of unmodified profilin
      actin. However, the cross-linked complex did not form filaments nor copolymerized
      with unmodified actin, but did interfere with elongation of actin filaments in a
      concentration-dependent manner. These results support a polymerization mechanism
      where the profilin-actin heterodimer binds to the (+)-end of actin filaments,
      followed by dissociation of profilin, and ATP hydrolysis and P(i) release from
      the actin subunit as it assumes its stable conformation in the helical filament.

PMID- 11844796
TI  - Role of de novo DNA methyltransferases and methyl CpG-binding proteins in gene
      silencing in a rat hepatoma.
AB  - The expression of metallothionein-I (MT-I), a known antioxidant, was suppressed
      in a transplanted rat hepatoma because of promoter methylation and was induced by
      heavy metals only after demethylation by 5-azacytidine (5-AzaC). Treatment of the
      tumor-bearing rats with 5-AzaC resulted in significant regression of the
      hepatoma. When the inhibitor-treated tumor was allowed to grow in a new host, MT
      I promoter was remethylated, which suggested de novo methylation. The activities
      of both de novo (3-fold) and maintenance DNA methyltransferases (DNMT) (5-fold)
      were higher in the hepatoma than in the host liver. The mRNA levels of the de
      novo methyltransferases DNMT3a and DNMT3b were 3- and 6-fold higher,
      respectively, in the tumor implicating transcriptional up-regulation of these two
      genes in this tissue. Immunohistochemical analysis showed exclusive localization
      of DNMT3a in the nuclei of both the liver and hepatoma, whereas DNMT3b was
      detected in the nuclei as well as the cytoplasm. Immunoblot assay showed that the
      levels of DNMT1, DNMT3a, and DNMT3b proteins in the hepatoma were 5-, 10-, and 4
      fold higher, respectively, than in the liver. The mRNA level of the major methyl
      CpG-binding protein (MeCP2) was 8-fold higher in the tumor compared with the
      liver. Immunohistochemical studies showed that MeCP2 is localized exclusively in
      the nuclei of both tissues. A chromatin immunoprecipitation assay demonstrated
      that MeCP2 was associated with the MT-I promoter in the hepatoma implicating its
      involvement in repressing the methylated promoter. Analysis of the DNA isolated
      from the liver and hepatoma by RLGS-M (restriction landmark genomic scanning with
      methylation-sensitive enzyme) (NotI) showed that many genes in addition to MT-I
      were methylated in the hepatoma. These data demonstrate suppression of the MT-I
      gene and probably other genes in a solid tumor by promoter methylation and have
      provided potential molecular mechanisms for the altered methylation profile of
      the genes in this tumor.

PMID- 11844799
TI  - Crystal structure of argininosuccinate synthetase from Thermus thermophilus HB8.
      Structural basis for the catalytic action.
AB  - Argininosuccinate synthetase catalyzes the ATP-dependent condensation of a
      citrulline with an aspartate to give argininosuccinate. The three-dimensional
      structures of the enzyme from Thermus thermophilus HB8 in its free form,
      complexed with intact ATP, and complexed with an ATP analogue (adenylyl
      imidodiphosphate) and substrate analogues (arginine and succinate) have been
      determined at 2.3-, 2.3-, and 1.95-A resolution, respectively. The structure is
      essentially the same as that of the Escherichia coli argininosuccinate
      synthetase. The small domain has the same fold as that of a new family of "N
      type" ATP pyrophosphatases with the P-loop specific for the pyrophosphate of ATP.
      However, the enzyme shows the P-loop specific for the gamma-phosphate of ATP. The
      structure of the complex form is quite similar to that of the native one,
      indicating that no conformational change occurs upon the binding of ATP and the
      substrate analogues. ATP and the substrate analogues are bound to the active site
      with their reaction sites close to one another and located in a geometrical
      orientation favorable to the catalytic action. The reaction mechanism so far
      proposed seems to be consistent with the locations of ATP and the substrate
      analogues. The reaction may proceed without the large conformational change of
      the enzyme proposed for the catalytic process.

PMID- 11844800
TI  - Transactivation-deficient Delta TA-p73 inhibits p53 by direct competition for DNA
      binding: implications for tumorigenesis.
AB  - The p53 family member p73 displays significant structural and functional homology
      to p53. However, instead of mutational inactivation, overexpression of wild-type
      p73 has been reported in various tumor types compared with normal tissues,
      arguing against a classical tumor suppressor function. Recently, N-terminally
      truncated, transactivation-deficient p73 isoforms (DeltaTA-p73) have been
      identified as a second class of p73 proteins. Because overexpression of p73 in
      tumors includes DeltaTA-p73, we further characterized these novel p73 isoforms.
      We show that DeltaTA-p73 retains DNA-binding competence but lacks transactivation
      functions, resulting in an inability to induce growth arrest and apoptosis.
      Importantly, DeltaTA-p73 acts as a dominant-negative inhibitor of p53 and full
      length p73 (TA-p73). We demonstrate that inhibition of p53 involves competition
      for DNA binding, whereas TA-p73 can be inhibited by direct protein-protein
      interaction. Further, we show that up-regulation of endogenous p73 just like
      ectopic overexpression of DeltaTA-p73 confers resistance to p53-mediated
      apoptosis induced by the chemotherapeutic agent H-7. Because inhibition of p53 is
      a common theme in human cancer, our data strongly support a role of DeltaTA-p73
      expression for tumor formation.

PMID- 11844801
TI  - Chlorella virus RNA triphosphatase. Mutational analysis and mechanism of
      inhibition by tripolyphosphate.
AB  - Chlorella virus RNA triphosphatase (cvRtp1) is the smallest member of a family of
      metal-dependent phosphohydrolases that includes the RNA triphosphatases of fungi,
      protozoa, poxviruses, and baculoviruses. The primary structure of cvRtp1 is more
      similar to that of the yeast RNA triphosphatase Cet1 than it is to the RNA
      triphosphatases of other DNA viruses. To evaluate the higher order structural
      similarities between cvRtp1 and the fungal enzymes, we performed an alanine scan
      of individual residues of cvRtp1 that were predicted, on the basis of the crystal
      structure of Cet1, to be located at or near the active site. Twelve residues
      (Glu(24), Glu(26), Asp(64), Arg(76), Lys(90), Glu(112), Arg(127), Lys(129),
      Arg(131), Asp(142), Glu(163), and Glu(165)) were deemed essential for catalysis
      by cvRtp1, insofar as their replacement by alanine reduced phosphohydrolase
      activity to <5% of the wild-type value. Structure-activity relationships were
      elucidated by introducing conservative substitutions at the essential positions.
      The mutational results suggest that the active site of cvRtp1 is likely to adopt
      a tunnel fold like that of Cet1 and that a similar constellation of side chains
      within the tunnel is responsible for metal binding and reaction chemistry.
      Nonetheless, there are several discordant mutational effects in cvRtp1 versus
      Cet1, which suggest that different members of the phosphohydrolase family vary in
      their reliance on certain residues within the active site tunnel. We found that
      tripolyphosphate and pyrophosphate were potent competitive inhibitors of cvRtp1
      (K(i) = 0.6 microm tripolyphosphate and 2.4 microm pyrophosphate, respectively),
      whereas phosphate had little effect. cvRtp1 displayed a weak intrinsic
      tripolyphosphatase activity (3% of its ATPase activity) but was unable to
      hydrolyze pyrophosphate.

PMID- 11844802
TI  - The RAVE complex is essential for stable assembly of the yeast V-ATPase.
AB  - Vacuolar proton-translocating ATPases are composed of a peripheral complex, V(1),
      attached to an integral membrane complex, V(o). Association of the two complexes
      is essential for ATP-driven proton transport and is regulated post
      translationally in response to glucose concentration. A new complex, RAVE, was
      recently isolated and implicated in glucose-dependent reassembly of V-ATPase
      complexes that had disassembled in response to glucose deprivation (Seol, J. H.,
      Shevchenko, A., and Deshaies, R. J. (2001) Nat. Cell Biol. 3, 384-391). Here, we
      provide evidence supporting a role for RAVE in reassembly of the V-ATPase but
      also demonstrate an essential role in V-ATPase assembly under other conditions.
      The RAVE complex associates reversibly with V(1) complexes released from the
      membrane by glucose deprivation but binds constitutively to cytosolic V(1)
      sectors in a mutant lacking V(o) sectors. V-ATPase complexes from cells lacking
      RAVE subunits show serious structural and functional defects even in glucose
      grown cells or in combination with a mutation that blocks disassembly of the V
      ATPase. RAVE small middle dotV(1) interactions are specifically disrupted in
      cells lacking V(1) subunits E or G, suggesting a direct involvement for these
      subunits in interaction of the two complexes. Skp1p, a RAVE subunit involved in
      many different signal transduction pathways, binds stably to other RAVE subunits
      under conditions that alter RAVE small middle dotV(1) binding; thus, Skp1p
      recruitment to the RAVE complex does not appear to provide a signal for V-ATPase
      assembly.

PMID- 11844803
TI  - Basic residues within the Kruppel zinc finger DNA binding domains are the
      critical nuclear localization determinants of EKLF/KLF-1.
AB  - EKLF/KLF-1 is an erythroid-restricted transcription factor essential for
      expression of the adult beta-globin gene. EKLF/KLF-1 is a 358-amino acid nuclear
      protein with an amino-terminal proline-rich domain and a carboxyl-terminal DNA
      binding domain. The nuclear localization signal (NLS) of EKLF/KLF-1 has not been
      empirically determined. We generated a series of epitope-tagged deletion and
      point mutants and assessed their subcellular localization. Our results delimit
      the NLS to the 83-amino acid (amino acids 276-358) DNA binding domain that
      consists of three Kruppel zinc fingers. All three zinc fingers are necessary for
      efficient nuclear localization; deletion of any individual finger results in
      cytoplasmic accumulation. Fusion of the three zinc fingers to green fluorescent
      protein (GFP) targeted GFP to the nucleus, demonstrating that the zinc finger
      domain is sufficient for nuclear localization. EKLF/KLF-1 containing histidine to
      alanine mutations that disrupt the structure of all three fingers retains
      appropriate nuclear localization, indicating that neither the tertiary structure
      of the zinc fingers nor specific DNA binding are necessary for nuclear
      localization. We demonstrate that basic residues within the fingers are the
      critical determinants for nuclear localization; mutations of these basic residues
      to alanine resulted in cytoplasmic mislocalization. The basic residues of all
      mammalian Kruppel zinc fingers are highly conserved; therefore we propose that
      these basic residues are a common NLS shared by all Kruppel family members.

PMID- 11844804
TI  - Clinical link between p53 and angiogenesis in lung cancer.

PMID- 11844805
TI  - Statistical prediction models, artificial neural networks, and the sophism "I am
      a patient, not a statistic".

PMID- 11844806
TI  - Cancer survivorship research: the best is yet to come.

PMID- 11844807
TI  - Chemoradiation for locally advanced cervical cancer: does it help?

PMID- 11844809
TI  - Microsatellite instability phenotype of tumors: genotyping or
      immunohistochemistry? The jury is still out.

PMID- 11844808
TI  - An evolving role for oral fluoropyrimidine drugs.

PMID- 11844810
TI  - Aberrant p53 expression correlates with expression of vascular endothelial growth
      factor mRNA and interleukin-8 mRNA and neoangiogenesis in non-small-cell lung
      cancer.
AB  - PURPOSE: To evaluate interactions between expressions of tumor suppressor gene
      p53 and angiogenic factors vascular endothelial cell growth factor (VEGF) and
      interleukin-8 (IL-8) and their effect on tumor angiogenesis and patient prognosis
      in non--small-cell lung cancer (NSCLC). PATIENTS AND METHODS: p53, VEGF, IL-8,
      and the microvessel endothelium were immunostained, and VEGF and IL-8 mRNA
      expression were quantified using the real-time quantitative reverse-transcription
      polymerase chain reaction in 65 NSCLC surgical specimens. Aberrant p53 expression
      was correlated with VEGF and IL-8 mRNA expression, microvessel count (MVC), other
      clinical-pathologic variables, and patients' survival. RESULTS: Tumors with high
      aberrant p53 expression showed significantly higher VEGF and IL-8 mRNA expression
      and MVC than those with low aberrant p53 expression (P <.001). When tested as a
      continuous variable, aberrant p53 expression correlated strongly and positively
      with VEGF and IL-8 mRNA expression and MVC (P <.0001). Tumors with high aberrant
      p53 expression were associated with mediastinal or distant lymph node metastasis
      (P =.006). Survival and postoperative relapse time were significantly shorter in
      patients with high aberrant p53 expression tumors than in those with low aberrant
      expression tumors (P <.0001). A significant difference in survival was also seen
      between patients with high and low tumoral VEGF mRNA expression and between those
      with high and low tumoral IL-8 mRNA expression (P <.0001). CONCLUSION: We report
      here for the first time that aberrant p53 expression is strongly positively
      correlated with VEGF mRNA and IL-8 mRNA expression in NSCLC. This result
      indicates that aberrant p53 expression may play a significant role in regulation
      of VEGF and IL-8 expression and be involved in controlling angiogenesis and
      explains the adverse prognosis of cancers with high aberrant p53 expression.

PMID- 11844811
TI  - Screening for lung cancer with low-dose helical computed tomography: anti-lung
      cancer association project.
AB  - PURPOSE: Because efficacy of lung cancer screening using chest x-ray is
      controversial and insufficient, other screening modalities need to be developed.
      To provide data on screening performance of low-dose helical computed tomography
      (CT) scanning and its efficacy in terms of survival, a one-arm longitudinal
      screening project was conducted. PATIENTS AND METHODS: A total of 1,611
      asymptomatic patients aged 40 to 79 years, 86% with smoking history, were
      screened by low-dose helical CT scan, chest x-ray, and 3-day pooled sputum
      cytology with a 6-month interval. RESULTS: At initial screening, the proportions
      of positive tests were 11.5%, 3.4%, and 0.8% with low-dose helical CT scan, chest
      x-ray, and sputum cytology, respectively. In 1,611 participants, 14 (0.87%) cases
      of lung cancer were detected, with 71% being stage IA disease and a mean tumor
      diameter of 19.8 mm. At repeated screening, the proportions of positive tests
      were 9.1%, 2.6%, and 0.7% with low-dose helical CT, chest x-ray, and sputum
      cytology, respectively. In 7,891 examinations, 22 (0.28%) cases of lung cancer
      were detected, with 82% being stage IA disease and a mean tumor diameter of 14.6
      mm. The 5-year survival rate for screen-detected lung cancer was 76.2% and 64.9%
      for initial and repeated screening, respectively. CONCLUSION: Screening with low
      dose helical CT has potential to improve screening efficacy in terms of reducing
      lung cancer mortality. An evaluation of efficacy using appropriate methods is
      urgently required.

PMID- 11844812
TI  - Novel artificial neural network for early detection of prostate cancer.
AB  - PURPOSE: Two artificial neural networks (ANN) for the early detection of prostate
      cancer in men with total prostate-specific antigen (PSA) levels from 2.5 to 4
      ng/mL and from 4 to 10 ng/mL were prospectively developed. The predictive
      accuracy of the ANN was compared with that obtained by use of conventional
      statistical analysis of standard PSA parameters. PATIENTS AND METHODS:
      Consecutive men with a serum total PSA level between 4 and 10 ng/mL (n = 974) and
      between 2.5 and 4 ng/mL (n = 272) were analyzed. A separate ANN model was
      developed for each group of patients. Analyses were performed to determine the
      presence of prostate cancer. RESULTS: The area under the receiver operator
      characteristic (ROC) curve (AUC) was 87.6% and 91.3% for the 2.5 to 4 ng/mL and 4
      to 10 ng/mL ANN models, respectively. For the latter model, the AUC generated by
      the ANN was significantly higher than that produced by the single variables of
      total PSA, percentage of free PSA, PSA density of the transition zone (TZ), and
      TZ volume (P <.01), but not significantly higher compared with multivariate
      analysis. For the 2.5 to 4 ng/mL model, the AUC of the ANN ROC curve was
      significantly higher than the AUCs for percentage of free PSA (P =.0239), PSA-TZ
      (P =.0204), and PSA density and total prostate volume (P <.01 for both).
      CONCLUSION: The predictive accuracy of the ANN was superior to that of
      conventional PSA parameters. ANN models might change the way patients referred
      for early prostate cancer detection are counseled regarding the need for prostate
      biopsy.

PMID- 11844813
TI  - Postchemotherapy ejaculatory azoospermia: fatherhood with sperm from testis
      tissue with intracytoplasmic sperm injection.
AB  - PURPOSE: To define the success of testis sperm extraction (TESE) and
      intracytoplasmic sperm injection (ICSI) in azoospermic men with a history of
      chemotherapy. PATIENTS AND METHODS: In a retrospective study, 23 men with
      ejaculatory azoospermia and a history of chemotherapy underwent TESE in a search
      for usable spermatozoa. In six patients cryopreserved tissue and in nine patients
      fresh tissue provided sperm for an ICSI cycle. Histologic analysis of the testis
      was performed in all patients. The presence or absence of sperm, fertilization
      rates with ICSI, and final outcomes of pregnancy were recorded. RESULTS:
      Spermatozoa were found on TESE in 15 (65.2%) of 23 men. On histopathology, the
      predominant pattern observed was Sertoli cell only (47.8%), followed by
      hypospermatogenesis (30.4%), mixed (17.4%), and late maturation arrest (4.3%).
      The fertilization rate was 65.2%, and ongoing/delivered pregnancies occurred in
      30.8% of cycles. Six healthy boys and four healthy girls have been born to date.
      CONCLUSION: Men who are azoospermic and have had prior cytotoxic therapy make up
      a small subgroup of males with nonobstructive azoospermia. It is important to
      define and characterize this subgroup and better define their true fertility
      potential. Approximately two thirds of these men have retrievable testis sperm,
      which may be used with ICSI to have healthy offspring. This exciting avenue for
      paternity has heretofore not been available to such patients.

PMID- 11844814
TI  - Phase II trial of weekly paclitaxel in patients with previously treated advanced
      urothelial cancer.
AB  - PURPOSE: We evaluated the efficacy and toxicity of weekly paclitaxel in patients
      with previously treated advanced urothelial cancer. PATIENTS AND METHODS:
      Patients with urothelial cancer who had received one prior systemic chemotherapy
      regimen for advanced disease and had evidence of disease progression were
      eligible for enrollment. Patients received paclitaxel 80 mg/m(2) by 1-hour
      intravenous infusion weekly. A cycle of therapy consisted of four weekly
      treatments. RESULTS: The study enrolled 31 patients. Mean age was 66 years, and
      45% of patients had three or more involved metastatic sites. Only 26% of patients
      had responded to prior chemotherapy. The median number of cycles delivered was
      three (range, one to eight) at a mean weekly paclitaxel dose of 79 mg/m(2). Three
      patients achieved a partial response (10%; 95% confidence interval, 0% to 20%).
      Median time to progression was 2.2 months, and median overall survival time was
      7.2 months. Therapy was well tolerated with minimal hematologic toxicity. Grade 3
      nonhematologic toxicities were also uncommon. CONCLUSION: Although the overall
      response rate to weekly paclitaxel in patients with previously treated advanced
      urothelial cancer was modest, the chemotherapy-refractory nature of the study
      population should be considered.

PMID- 11844815
TI  - Adrenocortical carcinoma: clinical, morphologic, and molecular characterization.
AB  - PURPOSE: To define multimolecular phenotypes of adrenocortical carcinoma (ACC)
      and to correlate outcome with morphologic and molecular parameters. PATIENTS AND
      METHODS: Clinical data were analyzed for 124 patients, histopathologic slides for
      67 primary tumors, and tissue specimens for 74 patients (38 primary and 36
      metastatic tumors) with ACC and for 38 normal adrenal tissue samples. Molecular
      expression profiles were investigated by immunohistochemistry. The prognostic
      significance of 12 gross and histologic parameters in 67 primary ACCs was
      evaluated. Morphologic and protein expression patterns were correlated with
      disease-specific survival (DSS). Univariate influence of prognostic factors on
      DSS was analyzed by log-rank test and multivariate analysis by Cox regression.
      RESULTS: The median follow-up period was 4.7 years. Significant predictors of DSS
      included distant metastasis at time of initial presentation; venous, capsular,
      and adjacent organ invasion; tumor necrosis, mitotic rate, atypical mitosis, and
      mdm-2 overexpression. Five-year DSS by number (one to six) of adverse histologic
      parameters was as follows: one to two, 84%; three to four, 37%; more than four,
      9% (P =.005). The phenotype Ki-67(-)p53(-)mdm-2(+)cyclinD1(-)Bcl-2(-)p21(-)p27(+)
      was observed in 83% of normal and 3% of malignant adrenal tissue (P =.01).
      Molecular phenotypic expression was more heterogeneous in malignant than in
      normal (10 v five phenotypes) adrenal tissue. CONCLUSION: Meticulous morphologic
      evaluation, mitotic count, and tumor stage are essential in determining prognosis
      for patients with ACC. Multimolecular phenotyping demonstrates that the molecular
      complexity and heterogeneity of these neoplasms are such that targeted therapy
      needs to be patient specific.

PMID- 11844816
TI  - Validation study of the accuracy of a postoperative nomogram for recurrence after
      radical prostatectomy for localized prostate cancer.
AB  - PURPOSE: A postoperative nomogram for prostate cancer was developed at Baylor
      College of Medicine. This nomogram uses readily available clinical and pathologic
      variables to predict 7-year freedom from recurrence after radical prostatectomy.
      We evaluated the predictive accuracy of the nomogram when applied to patients of
      four international institutions. PATIENTS AND METHODS: Clinical and pathologic
      data of 2,908 patients were supplied for validation, and 2,465 complete records
      were used. Nomogram-predicted probabilities of 7-year freedom from recurrence
      were compared with actual follow-up in two ways. First, the area under the
      receiver operating characteristic curve (AUC) was calculated for all patients and
      stratified by the time period of surgery. Second, calibration of the nomogram was
      achieved by comparing the predicted freedom from recurrence with that of an ideal
      nomogram. For patients in whom the pathologic report does not distinguish between
      focal and established extracapsular extension (an input variable of the
      nomogram), two separate calculations were performed assuming one or the other.
      RESULTS: The overall AUC was 0.80 when applied to the validation data set, with
      individual institution AUCs ranging from 0.77 to 0.82. The predictive accuracy of
      the nomogram was apparently higher in patients who were operated on between 1997
      and 2000 (AUC, 0.83) compared with those treated between 1987 and 1996 (AUC,
      0.78). Nomogram predictions of 7-year freedom from recurrence were within 10% of
      an ideal nomogram. CONCLUSION: The postoperative Baylor nomogram was accurate
      when applied at international treatment institutions. Our results suggest that
      accurate predictions may be expected when using this nomogram across different
      patient populations.

PMID- 11844817
TI  - Successful adenovirus-mediated wild-type p53 gene transfer in patients with
      bladder cancer by intravesical vector instillation.
AB  - PURPOSE: To study safety, feasibility, and biologic activity of adenovirus
      mediated p53 gene transfer in patients with bladder cancer. PATIENTS AND METHODS:
      Twelve patients with histologically confirmed bladder cancer scheduled for
      cystectomy were treated on day 1 with a single intratumoral injection of SCH
      58500 (rAd/p53) at cystoscopy at one dose level (7.5 x 10(11) particles) or a
      single intravesical instillation of SCH 58500 with a transduction-enhancing agent
      (Big CHAP) at three dose levels (7.5 x 10(11) to 7.5 x 10(13) particles).
      Cystectomies were performed in 11 patients on day 3, and transgene expression,
      vector distribution, and biologic markers of transgene activity were assessed by
      molecular and immunohistochemical methods in tumors and normal bladder samples.
      RESULTS: Specific transgene expression was detected in tissues from seven of
      eight assessable patients treated with intravesical instillation of SCH 58500 but
      in none of three assessable patients treated with intratumoral injection of SCH
      58500. Induction of RNA and protein expression of the p53 target gene p21/WAF1
      was demonstrated in samples from patients treated with SCH 58500 instillation at
      higher dose levels. Distribution studies after intravesical instillation of SCH
      58500 revealed both high transduction efficacy and vector penetration throughout
      the whole urothelium and into submucosal tumor cells. No dose-limiting toxicity
      was observed, and side effects were local and of transient nature. CONCLUSION:
      Intravesical instillation of SCH 58500 combined with a transduction-enhancing
      agent is safe, feasible, and biologically active in patients with bladder cancer.
      Studies to evaluate the clinical efficacy of this treatment in patients with
      localized high-risk bladder cancer are warranted.

PMID- 11844818
TI  - Phase III trial comparing radical radiotherapy with and without cisplatin
      chemotherapy in patients with advanced squamous cell cancer of the cervix.
AB  - PURPOSE: To test the hypothesis that cisplatin (CDDP) administered concurrently
      with standard radiotherapy (RT) would improve pelvic control and survival in
      patients with advanced squamous cell cancer of the cervix. PATIENTS AND METHODS:
      A total of 259 patients with International Federation of Gynecology and
      Obstetrics stage IB to IVA squamous cell cervical cancer with central disease
      greater-than-or-equal 5 cm or histologically confirmed pelvic lymph node
      involvement were randomized to receive RT (external-beam RT plus brachytherapy)
      plus weekly CDDP chemotherapy (40 mg/m(2)) (arm 1) or the same RT without
      chemotherapy (arm 2). RESULTS: A total of 253 patients were available for
      analysis. Median follow-up was 82 months. No significant difference was found in
      progression-free survival (P =.33). No significant difference in 3- and 5-year
      survival rates was found (69% v 66% and 62% v 58%, respectively; P =.42). The
      hazard ratio for survival (arm 2 to arm 1) was 1.10 (95% confidence interval,
      0.75 to 1.62). CONCLUSION: This study did not show a benefit to either pelvic
      control or survival by adding concurrent weekly CDDP chemotherapy in a dose of 40
      mg/m(2) to radical RT as given in this trial. Careful attention to RT details is
      important for achieving optimum outcome for patients with this disease.

PMID- 11844819
TI  - Increased cyclooxygenase-2 expression is associated with chemotherapy resistance
      and poor survival in cervical cancer patients.
AB  - PURPOSE: To investigate the expression of cyclooxygenase (COX-2) and its
      association with clinicopathologic parameters and clinical outcome in patients
      with cervical cancer. PATIENTS AND METHODS: The study included 84 patients with
      stage IB to IVA cervical cancer. Patients with early-stage cases (n = 21)
      underwent radical surgery, whereas patients with locally advanced cervical cancer
      (LACC) (n = 63) were first administered neoadjuvant cisplatin-based treatment and
      subjected to surgery in case of response. Immunohistochemical analysis was
      performed on paraffin-embedded sections with rabbit antiserum against COX-2.
      RESULTS: COX-2--integrated density values in the overall population ranged from
      1.2 to 82.3, with mean plus minus SE values of 27.4 plus minus 2.4. According to
      the chosen cutoff value, 36 (42.9%) of 84 patients were scored as COX-2 positive.
      COX-2 levels were shown to be highly associated with tumor susceptibility to
      neoadjuvant treatment. COX-2 showed a progressive increase from mean plus minus
      SE values of 19.9 plus minus 8.0 in complete responders through 31.5 plus minus
      3.5 in partial responses to 44.8 plus minus 3.9 in patients who were not
      responsive (P =.0054). When logistic regression was applied, only advanced stage
      and COX-2 positivity retained independent roles in predicting a poor chance of
      response to treatment. COX-2--positive patients had a shorter overall survival
      (OS) rate than COX-2--negative patients. In patients with LACC, the 2-year OS
      rate was 38% in COX-2--positive versus 85% in COX-2--negative patients (P
      =.0001). In the multivariate analysis, only advanced stage and COX-2 positivity
      retained independent negative prognostic roles for OS. CONCLUSION: The assessment
      of COX-2 status could provide additional information to identify patients with
      cervical cancer with a poor chance of response to neoadjuvant treatment and
      unfavorable prognosis.

PMID- 11844820
TI  - Epithelial ovarian cancer metastasizing to the brain: a late manifestation of the
      disease with an increasing incidence.
AB  - PURPOSE: We present the Royal Marsden Hospital experience of cerebral metastases
      from primary epithelial ovarian carcinoma (EOC) over the last 20 years and
      examine the evidence for an increasing incidence of EOC metastasizing to this
      site. PATIENTS AND METHODS: A total of 3,690 women with EOC were seen at the
      Royal Marsden Hospital from 1980 to 2000. Eighteen of these patients developed
      cerebral metastases. RESULTS: Median age at diagnosis of EOC was 52 years (range,
      39 to 67). All patients received at least one line of platinum-based
      chemotherapy; 56% (10 of 18) received more than one line of treatment; 17% (three
      of 18), two lines; 11% (two of 18), three lines; and 28% (five of 18), four
      lines. The median treatment interval between each line of chemotherapy was 12,
      18, and 4 months. The median interval between diagnosis and CNS relapse was 46
      months (range, 12 to 113), in comparison with 5 and 7.5 months for hematogenous
      relapse in lung or liver, respectively (P <.001). The incidence of CNS metastases
      in our population from 1980 to 1984 was 0.2%; from 1985 to 1989, 0%; from 1990 to
      1994, 0.3%; and from 1995 to 1999, 1.3% (P <.001). An analysis of data from the
      literature also suggests that the incidence of cerebral metastases from EOC has
      increased over time. CONCLUSION: CNS metastases in EOC are a rare and late
      manifestation of the disease, occurring in patients with a prolonged survival
      caused by repeated chemosensitive relapses. An analysis of our data and the data
      from the literature suggests that the incidence of metastasis at this site in
      patients with EOC is increasing.

PMID- 11844822
TI  - BRCA1 and BRCA2 mutation frequency in women evaluated in a breast cancer risk
      evaluation clinic.
AB  - PURPOSE: To determine the prevalence of BRCA1 and BRCA2 mutations in families
      identified in a breast cancer risk evaluation clinic. PATIENTS AND METHODS: One
      hundred sixty-four families seeking breast cancer risk evaluation were screened
      for coding region mutations in BRCA1 and BRCA2 by conformation-sensitive gel
      electrophoresis and DNA sequencing. RESULTS: Mutations were identified in 37
      families (22.6%); 28 (17.1%) had BRCA1 mutations and nine (5.5%) had BRCA2
      mutations. The Ashkenazi Jewish founder mutations 185delAG and 5382insC (BRCA1)
      were found in 10 families (6.1%). However, 6174delT (BRCA2) was found in only one
      family (0.6%) despite estimates of equal frequency in the Ashkenazi population.
      In contrast to other series, the average age of breast cancer diagnosis was
      earlier in BRCA2 mutation carriers (32.1 years) than in women with BRCA1
      mutations (37.6 years, P =.028). BRCA1 mutations were detected in 20 (45.5%) of
      44 families with ovarian cancer and 12 (75%) of 16 families with both breast and
      ovarian cancer in a single individual. Significantly fewer BRCA2 mutations (two
      [4.5%] of 44) were detected in families with ovarian cancer (P =.01). Eight
      families had male breast cancer; one had a BRCA1 mutation and three had BRCA2
      mutations. CONCLUSION: BRCA1 mutations were three times more prevalent than BRCA2
      mutations. Breast cancer diagnosis before 50 years of age, ovarian cancer, breast
      and ovarian cancer in a single individual, and male breast cancer were all
      significantly more common in families with BRCA1 and BRCA2 mutations, but none of
      these factors distinguished between BRCA1 and BRCA2 mutations. Evidence for
      reduced breast cancer penetrance associated with the BRCA2 mutation 6174delT was
      noted.

PMID- 11844821
TI  - Multicenter phase II study of a 28-day regimen of orally administered eniluracil
      and fluorouracil in the treatment of patients with anthracycline- and taxane
      resistant advanced breast cancer.
AB  - PURPOSE: Eniluracil (776C85), a potent inactivator of dihydropyrimidine
      dehydrogenase, allows fluorouracil (5-FU) to be administered orally on a schedule
      that simulates continuous-infusion 5-FU. The primary objective of this study was
      to estimate the objective tumor response rate of orally administered eniluracil
      and 5-FU in the treatment of anthracycline- and taxane-resistant advanced breast
      cancer. PATIENTS AND METHODS: Patients with anthracycline- and taxane-resistant
      advanced breast cancer were enrolled onto this open-label, phase II, multicenter
      study. Patients received orally administered 5-FU 1.0 mg/m(2) with eniluracil
      given in a 10:1 ratio (eniluracil:5-FU) twice daily for the first 28 days of each
      35-day cycle. RESULTS: Eighty-four patients were enrolled. Eight partial
      responses were observed in 84 patients (10%; 95% confidence interval [CI], 4.2%
      to 17.9%), and 20 patients (24%) had stable disease. The median duration of
      partial response was 20.1 weeks (95% CI, 12 to 26.7 weeks). The median duration
      of progression-free survival and overall survival for all patients was 9.9 weeks
      and 40.4 weeks, respectively. Most adverse events were grade 1 or 2 in intensity.
      Diarrhea, nausea, malaise/fatigue, vomiting, and mucositis were the most common
      treatment-related nonhematologic adverse events. The most frequently occurring
      grade 3 or 4 treatment-related adverse events were malaise/fatigue and diarrhea,
      occurring in 17% and 7% of patients, respectively. The incidence of grade 3 or 4
      hematologic toxicity was low. Grade 3 or 4 hyperbilirubinemia occurred in 17% of
      patients. CONCLUSION: Eniluracil-5-FU has modest antitumor activity and an
      acceptable safety profile in anthracycline- and taxane-resistant breast cancer.
      Treatment was convenient, and patient compliance was high.

PMID- 11844823
TI  - Clinical relevance of invasion factors urokinase-type plasminogen activator and
      plasminogen activator inhibitor type 1 for individualized therapy decisions in
      primary breast cancer is greatest when used in combination.
AB  - PURPOSE: A strong prognostic impact of urokinase-type plasminogen activator (uPA)
      and its inhibitor and plasminogen activator inhibitor type 1 (PAI-1) as
      individual factors is well established in breast cancer. The improvement in
      clinical risk assessment gained by combining these factors is evaluated here.
      PATIENTS AND METHODS: uPA and PAI-1 levels were prospectively measured by enzyme
      linked immunosorbent assay in tumor tissue extracts of 761 patients with primary
      breast cancer. RESULTS: In the clinically important subgroup of node-negative
      patients without adjuvant systemic therapy (n = 269; median follow-up, 60
      months), the clinical value of testing both uPA and PAI-1 is demonstrated. The
      criterion either or both high identifies with high sensitivity the patients at
      high relapse risk while keeping more than half in the low-risk group. uPA/PAI-1
      is the strongest predictor of disease-free survival and overall survival;
      patients with high uPA/PAI-1 have an increased relapse risk (P <.001; relative
      risk, 4.8; 95% confidence interval [CI], 2.5 to 9.1), in particular for early
      relapse. Even within risk groups stratified by established criteria (nodal or
      menopausal status, tumor size, grade, or steroid hormone receptors), uPA/PAI-1
      provides significant risk group discrimination. In the whole collective, the
      significant interaction between uPA/PAI-1 and adjuvant systemic therapy suggests
      a benefit from adjuvant therapy in high-risk patients as defined by uPA/PAI-1.
      CONCLUSION: The clinical relevance of the two tumor-invasion factors uPA and PAI
      1 is greatest when they are used in combination. The particular combination of
      uPA and PAI-1 (both low v either or both high) is superior to either factor alone
      and supports risk-adapted individualized therapy decisions.

PMID- 11844825
TI  - Dietary change after breast cancer: extent, predictors, and relation with
      psychological distress.
AB  - PURPOSE: Some women may try to cope with breast cancer by making lifestyle
      modifications, possibly in the hope of improving disease outcome. We assessed
      extent, predictors, and effect on psychological distress of dietary changes in
      the year after diagnosis among 250 women with newly diagnosed, nonmetastatic
      breast cancer. PATIENTS AND METHODS: Data came from medical records, and from
      interviews 3 days and 12 months after initial treatment. RESULTS: At 12 months,
      41% (n = 103) reported dietary changes at some time since diagnosis, with
      decreases in meat (77%) and increases in fruit and vegetable intake (72%) being
      the most frequent. Women reporting changes were more likely to be younger, to
      have positive nodes, to be receiving adjuvant therapy, and to be more distressed
      initially. The mean 0 to 12 month decrease in psychological distress was greater
      in women who reported changes (9 points) than those who did not (4.7 points) (P
      =.03), although regression toward the mean cannot be excluded. CONCLUSION: A
      sizable proportion of women made dietary changes on their own initiative. Most
      changes reported were generally consistent with current scientific hypotheses
      about dietary changes that might favorably affect prognosis. The profile of women
      reporting changes suggests a group with more concerns about recurrence, who may
      have initiated dietary change to help cope with and gain a sense of control over
      the disease, and possibly to improve prognosis. Our results suggest that newly
      diagnosed women could be receptive to explicit attention to diet as part of
      psychosocial care. However, this interest in dietary change may not, as yet, have
      been maximally channeled into trying to improve the care and quality of life of
      women facing diagnosis, treatments, and fears about recurrence.

PMID- 11844824
TI  - Communication between physicians and older women with localized breast cancer:
      implications for treatment and patient satisfaction.
AB  - PURPOSE: To identify factors associated with patient-physician communication and
      to examine the impact of communication on patients' perception of having a
      treatment choice, actual treatment received, and satisfaction with care among
      older breast cancer patients. MATERIALS AND METHODS: Data were collected from 613
      pairs of surgeons and their older (greater-than-or-equal 67 years) patients
      diagnosed with localized breast cancer. Measures of patients' self-reported
      communication included physician- and patient-initiated communication and the
      number of treatment options discussed. Logistic regression analyses were
      conducted to examine the relationships between communication and outcomes.
      RESULTS: Patients who reported that their surgeons mentioned more treatment
      options were 2.21 times (95% confidence interval [CI], 1.62 to 3.01) more likely
      to report being given a treatment choice, and 1.33 times (95% CI, 1.02 to 1.73)
      more likely to get breast-conserving surgery with radiation than other types of
      treatment. Surgeons who were trained in surgical oncology, or who treated a high
      volume of breast cancer patients (greater-than-or-equal 75% of practice), were
      more likely to initiate communication with patients (odds ratio [OR] = 1.62; 95%
      CI, 1.02 to 2.56; and OR = 1.68; 95% CI, 1.01 to 2.76, respectively). A high
      degree of physician-initiated communication, in turn, was associated with
      patients' perception of having a treatment choice (OR = 2.46; 95% CI, 1.29 to
      4.70), and satisfaction with breast cancer care (OR = 2.13; 95% CI, 1.17 to 3.85)
      in the 3 to 6 months after surgery. CONCLUSION: Greater patient-physician
      communication was associated with a sense of choice, actual treatment, and
      satisfaction with care. Technical information and caring components of
      communication impacted outcomes differently. Thus, the quality of cancer care for
      older breast cancer patients may be improved through interventions that improve
      communication within the physician-patient dyad.

PMID- 11844826
TI  - Comparison of the systemic and intratumoral effects of tamoxifen and the
      aromatase inhibitor vorozole in postmenopausal patients with primary breast
      cancer.
AB  - PURPOSE: To determine biologic differences, if any, between presurgical endocrine
      treatment with an aromatase inhibitor (vorozole) and tamoxifen in patients with
      postmenopausal primary breast cancer. PATIENTS AND METHODS: Randomization was to
      12 weeks of 2.5 mg of vorozole per day or 20 mg of tamoxifen per day, both
      orally. Clinical response was assessed monthly together with serum sex hormone
      binding globulin (SHBG), luteinizing hormone (LH), follicle-stimulating hormone
      (FSH), estrogens (E1, E2, and E1S), lipids, insulin-like growth factor-1 (IGF-1),
      and bone metabolites (CrossLaps CTx). Tissue samples for Ki67, apoptotic index
      (AI), estrogen receptor, and progesterone receptor were collected at 0, 2, and 12
      weeks. RESULTS: Ki67 fell by 58% and 43% (means) at 2 weeks in the vorozole and
      tamoxifen patients, respectively (P =.13). In the vorozole group, the
      correlations of proportional changes in Ki67 at 2 weeks with tumor volume changes
      and clinical response at 12 weeks were not significant (P =.09) and marginally
      significant (P =.04), respectively. Serum lipids did not differ between groups.
      Serum levels of EI, E2, and E1S were suppressed markedly by vorozole, whereas
      levels of SHBG increased and LH and FSH fell significantly with tamoxifen. IGF-1
      levels fell significantly with tamoxifen (P =.001) compared with the
      nonsignificant rise with vorozole. Twelve-week CTx values fell by 19% with
      tamoxifen (P =.006) and rose by 11% with vorozole (P =.15). CONCLUSION: The
      correlation with vorozole of Ki67 with volume and clinical response supports this
      as an intermediate marker. The nonsignificant effects on bone and lipid
      metabolism by the aromatase inhibitor may be important to consider for adjuvant
      and potential prevention strategies.

PMID- 11844827
TI  - Assessment of coronary heart disease morbidity and mortality after radiation
      therapy for early breast cancer.
AB  - PURPOSE: To assess the risk of fatal and nonfatal myocardial infarction (MI)
      after breast-conserving surgery (BCS) and radiation therapy (RT) for left-sided
      breast cancer. PATIENTS AND METHODS: A hospital-based retrospective cohort
      linkage study of all breast cancer patients registered at the Princess Margaret
      Hospital (PMH), Toronto, Canada, between 1982 and 1988 who were treated with
      postlumpectomy RT was performed. Available identifiers for the study cohort were
      linked to two province-wide health files: the Canadian Institute for Health
      Information Hospitalization File and the Ontario Mortality Database. Admissions
      to hospital for MI and deaths attributable to MI were identified. The relevant
      original health records were abstracted to verify the diagnosis of MI according
      to diagnostic criteria used in the World Health Organization multinational
      monitoring of trends and determinants in cardiovascular disease (MONICA) project.
      We compared incidence of MI in the study cohort with the general population and
      incidence of MI after therapy for left- versus right-sided breast cancer.
      RESULTS: A cohort of 2,128 patients was identified. The median length of follow
      up was 10.2 years. The incidence of MI in the study cohort was comparable to that
      in an age-matched general population of women in Ontario. There were 70 coronary
      events among 56 patients after breast irradiation. According to MONICA criteria,
      53 and six events were characterized as definite and possible MIs, respectively.
      Eleven events did not satisfy MONICA criteria for MI. Twenty-six patients treated
      for left-sided and 23 patients treated for right-sided breast cancer experienced
      at least one definite or possible MI (log-rank test, P =.66). There were eight
      fatal MIs among the left-sided group and six among the right-sided group. There
      was no excess of other cardiac diseases among patients who received left-sided
      radiotherapy compared to the right-sided group. CONCLUSION: We have found no
      evidence for excess morbidity and mortality from coronary artery disease among
      women treated with RT to the left breast after BCS at 10.2 years of follow-up.
      Longer follow-up is required to confirm that excess cardiac disease has been
      completely avoided.

PMID- 11844828
TI  - Immunohistochemistry versus microsatellite instability testing in phenotyping
      colorectal tumors.
AB  - PURPOSE: To compare microsatellite instability (MSI) testing with
      immunohistochemical (IHC) detection of hMLH1 and hMSH2 in colorectal cancer.
      PATIENTS AND METHODS: Colorectal cancers from 1,144 patients were assessed for
      DNA mismatch repair deficiency by two methods: MSI testing and IHC detection of
      hMLH1 and hMSH2 gene products. High-frequency MSI (MSI-H) was defined as more
      than 30% instability of at least five markers; low-level MSI (MSI-L) was defined
      as 1% to 29% of loci unstable. RESULTS: Of 1,144 tumors tested, 818 showed intact
      expression of hMLH1 and hMSH2. Of these, 680 were microsatellite stable (MSS), 27
      were MSI-H, and 111 were MSI-L. In all, 228 tumors showed absence of hMLH1
      expression and 98 showed absence of hMSH2 expression: all were MSI-H. CONCLUSION:
      IHC in colorectal tumors for protein products hMLH1 and hMSH2 provides a rapid,
      cost-effective, sensitive (92.3%), and extremely specific (100%) method for
      screening for DNA mismatch repair defects. The predictive value of normal IHC for
      an MSS/MSI-L phenotype was 96.7%, and the predictive value of abnormal IHC was
      100% for an MSI-H phenotype. Testing strategies must take into account
      acceptability of missing some cases of MSI-H tumors if only IHC is performed.

PMID- 11844829
TI  - Prognostic significance of cytokeratin-20 reverse transcriptase polymerase chain
      reaction in lymph nodes of node-negative colorectal cancer patients.
AB  - PURPOSE: Approximately 20% to 30% of patients with curatively resected, node
      negative (pN0) colorectal cancer die of tumor recurrence, which can be caused by
      minimal residual disease. To identify patients with an increased risk of tumor
      recurrence and evaluate the prognostic value of cytokeratin-20 (CK-20), we
      detected CK-20-positive cells in histopathologically tumor-free lymph nodes (pN0)
      of patients with colorectal cancer. PATIENTS AND METHODS: Two peritumoral lymph
      nodes each from 85 patients with completely resected (R0) colorectal cancer
      without lymph node metastases (pN0) by routine examination were analyzed using a
      CK-20-specific reverse transcriptase polymerase chain reaction (RT-PCR) and
      compared with CK-20-specific immunohistochemistry (IHC). The results were
      correlated with histopathologic findings and with survival. RESULTS: CK-20 RT-PCR
      was positive in 44 patients (52%) and detected 83% of cancer-related death.
      Positive RT-PCR was significantly correlated with poorer overall survival (P
      <.009). Comparing RT-PCR with IHC, 13 patients with positive RT-PCR were
      identified, where the CK-20 expression was caused by tumor cell contamination
      located exclusively outside the lymph node capsule and had no prognostic impact.
      Defining these 13 patients as RT-PCR negative improved specificity of the RT-PCR
      assay from 57% to 75%. The 5-year overall survival of the 31 RT-PCR-positive
      patients was 71%, compared with 96% in the 54 negative patients (P <.001).
      Multivariate analysis showed expression of CK-20 mRNA to be an independent
      prognostic factor with a relative risk of cancer-related death of 6.1.
      CONCLUSION: CK-20 RT-PCR in peritumoral histopathologic tumor-free (pN0) lymph
      nodes of colorectal cancer is an independent prognostic factor for overall
      survival. Additional CK-20 IHC improves the specificity and prognostic value of
      RT-PCR for cancer-related death.

PMID- 11844830
TI  - Role of health-related quality of life in palliative chemotherapy treatment
      decisions.
AB  - PURPOSE: To determine the frequency with which health-related quality-of-life
      (HRQL) considerations lead to modification or discontinuation of palliative
      chemotherapy, and the association between physicians' ratings of patients' HRQL
      and such treatment decisions. METHODS: Four consecutive medical consultations of
      203 patients receiving outpatient palliative chemotherapy were tape-recorded and
      the content was analyzed to determine the frequency of and reasons for treatment
      alterations. Physicians rated their patients' HRQL by using the COOP/WONCA health
      assessment charts. Data on tumor response and treatment toxicity were obtained
      from the audiotapes and, when necessary, were confirmed by medical chart audits.
      RESULTS: Treatment was modified in 54 cases (26%) and discontinued in 40 (20%).
      The primary reasons for modifying treatment were toxicity (n = 22), HRQL
      considerations (n = 18), and tumor progression (n = 14). The primary reasons for
      discontinuation of treatment were tumor progression (n = 23), HRQL considerations
      (n = 6), and toxicity (n = 3). For eight patients, a combination of tumor
      progression and HRQL issues resulted in discontinuation of treatment. Treatment
      decisions were associated significantly with physicians' global ratings of
      patients' HRQL but not with more specific HRQL domains. In the presence of tumor
      progression or serious toxicity, HRQL considerations played little or no role in
      treatment decisions. Furthermore, approximately 70% of patients without evidence
      of tumor progression or toxicity, but with seriously impaired HRQL, continued to
      receive their treatment as planned. CONCLUSION: Contrary to previous findings
      based on physicians' self-report data, HRQL considerations seem to play a
      relatively minor role in decisions regarding modification or discontinuation of
      palliative chemotherapy.

PMID- 11844831
TI  - Quantitatively determined survivin expression levels are of prognostic value in
      human gliomas.
AB  - PURPOSE: Survivin is a novel antiapoptotic gene that has been recently cloned and
      characterized. Its expression has been found to be of prognostic significance in
      several tumor types. This is the first study on the prognostic significance of
      survivin expression in human gliomas. MATERIALS AND METHODS: We used quantitative
      Western blot analysis with densitometry to determine survivin protein expression
      levels in 92 glioma cases for which frozen tissue was available for analysis.
      Survivin positivity and expression levels were correlated with histopathologic
      features of the tumors, apoptosis (as measured by cleaved, or activated, caspase
      3 levels), and clinical outcome. RESULTS: Survivin expression has clear
      prognostic value in human gliomas. Patients with detectable survivin expression
      had significantly shorter overall survival times (P <.0001) compared with those
      without detectable expression when all glioma patients were considered. Although
      glioblastoma multiforme (GBM) patients had significantly higher rates of survivin
      positivity and higher levels of survivin expression (P <.0001) than their non-GBM
      counterparts, the prognostic value of survivin expression seemed to be
      independent of histology alone. Survivin-positive GBM patients had significantly
      shorter overall survival times compared with survivin-negative GBM patients (P
      <.0001). Likewise, survivin-positive non-GBM patients had shorter survival times
      compared with survivin-negative non-GBM patients (P =.029). Furthermore,
      increasing levels of survivin expression significantly correlated with reduced
      survival times when all glioma patients were considered, and markedly so for GBM
      patients (P <.0001). Increasing survivin levels significantly correlated with
      reduced expression of cleaved caspase 3, indicating its association with
      antiapoptotic activity. CONCLUSION: Survivin positivity and protein expression
      levels, as determined quantitatively, are of significant prognostic value in
      human gliomas and seem to be associated with reduced apoptotic capacity of these
      tumors.

PMID- 11844832
TI  - Loss of MDA-7 expression with progression of melanoma.
AB  - PURPOSE: Ectopic transfer of the melanoma differentiation-associated gene-7 (mda
      7) has been shown in vitro to suppress growth and induce apoptosis in a variety
      of human tumor cell lines; similar effects are not elicited in normal cells.
      Thus, the mda-7 gene seems to function as a novel tumor suppressor, and there is
      interest in the potential of mda-7 gene transfer as cancer therapy. The objective
      of this study was to determine if MDA-7 protein is lost during primary melanoma
      progression from superficial to invasive stages and from localized to metastatic
      tumor. As a secondary objective, we analyzed MDA-7 protein expression in primary
      melanomas for correlation with predictors of outcome and with survival. MATERIALS
      AND METHODS: MDA-7 protein expression was evaluated by immunohistochemistry in 41
      primary melanomas and 41 metastases, including 24 paired samples. Each sample was
      scored for the percentage of positive cells and the overall intensity of
      immunolabeling. RESULTS: Significant decreases in MDA-7 immunostaining, reflected
      in both number and intensity scores, were observed when comparing the
      intraepidermal and superficially invasive portions with the deeply invasive
      portions of primary tumors. Significant differences were also observed when
      comparing primary tumors to paired metastases. CONCLUSION: Downregulation of MDA
      7 expression in primary melanomas facilitates progression to invasive and
      metastatic stages. These data support the development of Ad-mda7 as gene therapy
      for advanced melanoma.

PMID- 11844833
TI  - Phase I trial of adoptive immunotherapy with cytolytic T lymphocytes immunized
      against a tyrosinase epitope.
AB  - PURPOSE: To study distribution and toxicity of cytolytic T lymphocytes (CTLs)
      against a single melanoma epitope. PATIENTS AND METHODS: CD8(+) T cells obtained
      by leukapheresis from 10 patients with disseminated HLA-A2.1(+), tyrosinase
      positive melanomas were immunized in vitro against tyrosinase(369-377)
      (YMNGTMSQV). Drosophila cells transduced with HLA-A2.1, CD80, and CD54
      (intracellular adhesion molecule-1) were used for priming, followed by two rounds
      of immunization with mononuclear cells as antigen-presenting cells. 1 x 10(8) CTL
      were infused intravenously (IV) on day 1. CTL frequency was measured by limiting
      dilutions in five patients. (111)In labeling and scintigraphy measured
      distribution of CTL in next five. Five days later, 1 x 10(8) CTLs were infused on
      4 successive days to both groups. Immunohistology of response was judged by
      biopsies. RESULTS: Infusions were nontoxic. CTLs were undetectable in the blood,
      going to lungs within 5 minutes. At 4, 24, and 72 hours, they were found in liver
      and spleen. Lesions were visualized by scintiscans in one responding patient
      where two subcutaneous nodules were noted at 4 and 24 hours. A second patient had
      a partial response and remains alive with disease 2 years later. CD8(+) T cells
      were found in lesions of responders, associated with the presence of HLA-A2
      molecules and tyrosinase. Two nonresponders without tyrosinase and HLA-A2
      molecules had a paucity of CD8(+) T cells in their lesions. Whether the CD8(+) T
      cells in lesions of responders were those we had reinfused is uncertain.
      CONCLUSION: CTLs immunized against a single melanoma epitope were nontoxic but
      did not specifically localize to tumor sites. Nevertheless, two patients had
      disease regression. Additional therapeutic studies with specifically immunized
      CTL seem justified.

PMID- 11844834
TI  - Hodgkin's disease in the elderly: improved treatment outcome with a doxorubicin
      containing regimen.
AB  - PURPOSE: Hodgkin's disease (HD) is a malignancy that displays a bimodal age
      distribution. Previous reports of treatment in patients greater-than-or-equal 60
      years have found a poor outcome, particularly in patients with advanced disease.
      Because of an improved side-effect profile, the regimen of chlorambucil,
      vinblastine, procarbazine, and prednisone (ChlVPP) has been proposed for use in
      elderly patients. PATIENTS AND METHODS: From September 1982 to May 1998, 262
      patients with previously untreated HD received either ChlVPP (n = 176) or ChlVPP
      plus doxorubicin/bleomycin/vincristine (ChlVPP/ABV hybrid; n = 86). Fifty-six
      patients were greater-than-or-equal 60 years old, and 206 were younger than 60
      years. RESULTS: The 5-year overall survival (OS; 87% v 39%) and the 5-year event
      free survival (EFS; 75% v 31%) favored patients younger than 60 years of age.
      Prognostic factors analyzed in patients greater-than-or-equal 60 years of age,
      other than type of therapy, included sex, stage, Karnofsky performance score,
      lactic dehydrogenase, number of extranodal sites, B symptoms, size of largest
      mass, and histologic subtype. In patients older than 60 years, none of the
      clinical features was a statistically significant predictor of EFS; however,
      ChlVPP/ABV hybrid was associated with a decreased risk of an event (relative
      risk, 0.40; 95% confidence interval, 0.19 to 0.83; P =.014) compared with ChlVPP.
      The 5-year OS for patients greater-than-or-equal 60 years who received ChlVPP was
      30%, compared with 67% for those patients receiving the ChlVPP/ABV regimen (P
      =.0086) CONCLUSION: Patients greater-than-or-equal 60 years with HD who require
      chemotherapy are better treated with ChlVPP/ABV hybrid than with ChlVPP alone.

PMID- 11844835
TI  - Minimal residual disease tests provide an independent predictor of clinical
      outcome in adult acute lymphoblastic leukemia.
AB  - PURPOSE: Investigation of minimal residual disease (MRD) in childhood acute
      lymphoblastic leukemia (ALL) using molecular markers has proven superior to other
      standard criteria (age, sex, and WBC) in distinguishing patients at high,
      intermediate, and low risk of relapse. The aim of our study was to determine
      whether MRD investigation is valuable in predicting outcome in Philadelphia
      negative adult patients with ALL. PATIENTS AND METHODS: MRD was assessed in 85
      adult patients with B-lineage ALL by semiquantitative immunoglobulin H gene
      analysis on bone marrow samples collected during four time bands in the first 24
      months of treatment. Fifty patients received chemotherapy only and 35 patients
      received allogeneic (n = 19) or autologous (n = 16) bone marrow transplantation
      (BMT) in first clinical remission. The relationship between MRD status and
      clinical outcome was investigated and compared with age, sex, immunophenotype,
      and presenting WBC count. RESULTS: Fisher's exact test established a
      statistically significant concordance between MRD results and clinical outcome at
      all times. Disease-free survival (DFS) rates for MRD-positive and -negative
      patients and log-rank testing established that MRD positivity was associated with
      increased relapse rates at all times (P <.05) but was most significant at 3 to 5
      months after induction and beyond. MRD status after allogeneic BMT rather than
      before was found to be an important predictor of outcome in 19 adult patients
      with ALL tested. In patients receiving autologous BMT (n = 16), the MRD status
      before BMT was more significant (P =.005). CONCLUSION: The association of MRD
      test results and DFS was independent of and greater than other standard
      predictors of outcome and is therefore important in determining treatment for
      individual patients.

PMID- 11844836
TI  - Determination of the molecular relationship between multiple tumors within one
      patient is of clinical importance.
AB  - PURPOSE: To determine the molecular relationship between multiple tumors within
      one patient and to evaluate the impact of this knowledge on clinical management.
      PATIENTS AND METHODS: In 25 consecutive patients with multiple tumors, proven by
      histology and immunohistochemistry to be identical, molecular aberrations were
      determined. Each patient had at least one lesion in the lung or head and neck
      region. Loss of heterozygosity (LOH) and p53 aberration analyses were carried
      out, and similar aberration profiles suggest clonality and metastasis whereas
      different profiles suggest independent primary tumors. RESULTS: The molecular
      determinations indicated that 12 patients had a probable second primary tumor and
      10 patients had a metastasis of the first lesion. In three patients, both an
      independent primary tumor and a metastasis were present. The molecular findings
      determined the course of additional treatment in all 10 patients with metastases,
      in all three patients with both a second primary tumor and a metastasis, and in
      seven of 12 patients with a second primary tumor. CONCLUSION: By comparing DNA
      alterations of multiple tumors within one patient, the relationship between the
      tumors can be assessed. This study shows that in 20 of 25 patients, knowledge of
      the nature of both lesions was essential in clinical decision making.
      Furthermore, after thorough analysis of the five cases where clinical decision
      making was not influenced, there was in retrospect no clear indication for LOH or
      p53 analysis. Because these molecular analyses can be performed on routine
      specimens, they can be applied in almost all patients.

PMID- 11844837
TI  - Phase I clinical and pharmacologic trial of intravenous estramustine phosphate.
AB  - PURPOSE: To determine the dose-limiting toxicities, maximum-tolerated dose, and
      pharmacokinetics of intravenous estramustine phosphate (IV EMP). PATIENTS AND
      METHODS: A total of 31 patients with hormone-refractory prostate cancer received
      IV EMP as a 30- to 90-minute infusion weekly (n = 28) or for 3 consecutive days
      followed by a single weekly dose (n = 3). IV EMP dose was escalated from 500 to
      3,000 mg/m(2). Pharmacokinetics of EMP and the metabolites estramustine (EaM),
      estromustine (EoM), estradiol, and estrone were assessed after weeks 1 and 4 of
      treatment. RESULTS: The initial IV EMP infusion caused perineal discomfort that
      was ameliorated by lengthening the infusion time. Other common toxicities were
      grade 1 to 2 hepatotoxicity, nausea or vomiting, and fatigue or malaise. Lower
      extremity thrombosis occurred in one patient, and two others developed upper
      extremity thrombosis associated with venous infusion catheters. Dose-limiting
      fatigue and hypotension occurred at 3,000 mg/m(2), and cumulative fatigue
      developed after multiple cycles at 2,500 mg/m(2). Mean EMP clearance, estimated
      steady-state volume of distribution, and elimination half-life were 3.7 L/h, 10.6
      L, and 3.7 hours, respectively. Variability of EMP clearance was 21%, and
      variation in area under the curve per dose for the metabolites was 28% to 36%.
      Elimination half-lives of EoM and EaM were 110 hours and 64 hours, and peak
      plasma concentrations of these active metabolites exceeded 10 micromol/L after IV
      EMP doses greater-than-or-equal 2,000 mg/m(2). CONCLUSION: High-dose IV EMP can
      be administered safely as a weekly short infusion to patients with HRPC. High
      peak concentrations of active metabolites after IV EMP may provide an advantage
      over oral EMP in antimicrotubule drug combinations.

PMID- 11844838
TI  - Weight loss in breast cancer patient management.
AB  - PURPOSE: To systematically review and summarize evidence relevant to obesity and
      breast cancer clinical outcome, potential hormonal mediating mechanisms, and the
      current status of weight loss interventions for chronic disease management.
      METHODS: A comprehensive, formal literature review was conducted to identify
      5,687 citations with key information from 159 references summarized in text and
      tables. This process included a search for all breast cancer studies exploring
      associations among survival or recurrence and obesity at diagnosis or weight gain
      after diagnosis using prospective criteria. RESULTS: On the basis of
      observational studies, women with breast cancer who are overweight or gain weight
      after diagnosis are found to be at greater risk for breast cancer recurrence and
      death compared with lighter women. Obesity is also associated with hormonal
      profiles likely to stimulate breast cancer growth. Recently, use of weight loss
      algorithms proven successful in other clinical settings that incorporate dietary
      therapy, physical activity, and ongoing behavior therapy have been endorsed by
      the National Institutes of Health and other health agencies. CONCLUSION: Although
      definitive weight loss intervention trials in breast cancer patients remain to be
      conducted, the current evidence relating increased body weight to adverse breast
      cancer outcome and the documented favorable effects of weight loss on clinical
      outcome in other comorbid conditions support consideration of programs for weight
      loss in breast cancer patients. Recommendations for the clinical care of
      overweight or obese breast cancer patients are offered.

PMID- 11844839
TI  - When the mirror doesn't reflect it at all.

PMID- 11844840
TI  - Mortality associated with irinotecan plus bolus fluorouracil/leucovorin.

PMID- 11844841
TI  - Hypersensitivity reactions to oxaliplatin: cross-reactivity to carboplatin and
      the introduction of a desensitization schedule.

PMID- 11844842
TI  - Ovarian and papillary-serous peritoneal carcinoma: pilot study with thalidomide.

PMID- 11844843
TI  - Lack of tumor necrosis factor-related apoptosis-inducing ligand but presence of
      its receptors in the human brain.
AB  - Apoptosis mediated by members of the tumor necrosis factor (TNF)-nerve growth
      factor superfamily plays a crucial role in the interaction of the nervous and the
      immune system. On the one hand, it is involved in the defense mechanisms of the
      brain, the immune privilege. On the other hand, it is involved in the induction
      of glial-neuronal cell death in neuroinflammatory diseases. Here, we show that in
      contrast to the other known death ligands, TNF-related apoptosis-inducing ligand
      (TRAIL) is not constitutively expressed in the human brain, whereas both
      apoptosis-mediating and apoptosis-blocking TRAIL receptors are found on neurons,
      astrocytes, and oligodendrocytes. Thus, the brain differs from other immune
      privileged organs, such as the placenta, with the TRAIL receptor-TRAIL system not
      being part of the immune privilege of the brain. Conversely, this death receptor
      ligand system might well play an important role in T cell-mediated autoimmune
      diseases of the CNS such as multiple sclerosis.

PMID- 11844844
TI  - Working memory neurons in pigeons.
AB  - Working memory, the ability to temporarily store and manipulate currently
      relevant information, is required for most cognitive faculties. In humans and
      other mammals, the prefrontal cortex (PFC) provides the underlying neural network
      for these processes. Within the PFC, working memory neurons display sustained
      elevated activity while holding active an internal representation of the relevant
      stimulus during its physical absence or retaining a motor plan for the
      forthcoming response. Working memory, however, is not a hallmark of higher
      vertebrates endowed with a neocortex. Birds also master complex cognitive
      problems invoking working memory, but they lack a laminated neocortex. Behavioral
      studies in pigeons show that the neostriatum caudolaterale (NCL) plays a central
      role in executive functions, such as working memory and response control. For
      neurons in the NCL of pigeons, we show activity changes during the delay of a
      working memory task, which were similar to those observed in PFC neurons and were
      related to the successful holding of information in memory and to the subsequent
      behavior. Thus, although the anatomical and morphological structure of the
      neuronal substrate in birds is radically different from the mammalian neocortical
      architecture, the neuronal mechanisms evolved to master equivalent cognitive
      demands seem to be very similar.

PMID- 11844845
TI  - Distinct gamma-band evoked responses to speech and non-speech sounds in humans.
AB  - To understand spoken language, the human brain must have fast mechanisms for the
      representation and identification of speech sounds. Stimulus-induced
      synchronization of neural activity at gamma frequencies (20-80 Hz), occurring in
      humans at 200-300 msec from stimulus onset, has been suggested to be a possible
      mechanism for neural object representation. Auditory and visual stimuli also
      evoke an earlier (peak <100 msec) gamma oscillation, but its dependence on high
      level stimulus parameters and, thereby, its involvement in object representation
      has remained unclear. Using whole-scalp magnetoencephalography, we show here that
      responses evoked by speech and non-speech sounds differed in the gamma-frequency
      but not in the low-frequency (0.1-20 Hz) band as early as 40-60 msec from
      stimulus onset. The gamma-band responses to the speech sound peaked earlier in
      the left than in the right hemisphere, whereas those to the non-speech sound
      peaked earlier in the right hemisphere. For the speech sound, there was no
      difference in the response amplitude between the hemispheres at low (20-45 Hz)
      gamma frequencies, whereas for the non-speech sound, the amplitude was larger in
      the right hemisphere. These results suggest that evoked gamma-band activity may
      indeed be sensitive to high-level stimulus properties and may hence reflect the
      neural representation of speech sounds. Consequently, speech-specific neuronal
      processing may commence no later than 40-60 msec from stimulus onset, possibly in
      the form of activation of language-specific memory traces.

PMID- 11844846
TI  - Homocysteine and dementias.

PMID- 11844847
TI  - Pure red-cell aplasia and antierythropoietin antibodies in patients treated with
      recombinant erythropoietin.
AB  - BACKGROUND: Within a period of three years, we identified 13 patients in whom
      pure red-cell aplasia developed during treatment with recombinant human
      erythropoietin (epoetin). We investigated whether there was an immunologic basis
      for the anemia in these patients. METHODS: Serum samples from the 13 patients
      with pure red-cell aplasia were tested for neutralizing antibodies that could
      inhibit erythroid-colony formation by normal bone marrow cells in vitro. The
      presence of antierythropoietin antibodies was identified by means of binding
      assays with the use of radiolabeled intact, deglycosylated, or denatured epoetin.
      RESULTS: Serum from all 13 patients blocked the formation of erythroid colonies
      by normal bone marrow cells. The inhibition was reversed by epoetin. Antibodies
      from 12 of the 13 patients bound only conformational epitopes in the protein
      moiety of epoetin; serum from the remaining patient bound to both conformational
      and linear epitopes in erythropoietin. In all the patients, the antibody titer
      slowly decreased after the discontinuation of treatment with epoetin.
      CONCLUSIONS: Neutralizing antierythropoietin antibodies and pure red-cell aplasia
      can develop in patients with the anemia of chronic renal failure during treatment
      with epoetin.

PMID- 11844848
TI  - Plasma homocysteine as a risk factor for dementia and Alzheimer's disease.
AB  - BACKGROUND: In cross-sectional studies, elevated plasma homocysteine levels have
      been associated with poor cognition and dementia. Studies of newly diagnosed
      dementia are required in order to establish whether the elevated homocysteine
      levels precede the onset of dementia or result from dementia-related nutritional
      and vitamin deficiencies. METHODS: A total of 1092 subjects without dementia (667
      women and 425 men; mean age, 76 years) from the Framingham Study constituted our
      study sample. We examined the relation of the plasma total homocysteine level
      measured at base line and that measured eight years earlier to the risk of newly
      diagnosed dementia on follow-up. We used multivariable proportional-hazards
      regression to adjust for age, sex, apolipoprotein E genotype, vascular risk
      factors other than homocysteine, and plasma levels of folate and vitamins B12 and
      B6. RESULTS: Over a median follow-up period of eight years, dementia developed in
      111 subjects, including 83 given a diagnosis of Alzheimer's disease. The
      multivariable-adjusted relative risk of dementia was 1.4 (95 percent confidence
      interval, 1.1 to 1.9) for each increase of 1 SD in the log-transformed
      homocysteine value either at base line or eight years earlier. The relative risk
      of Alzheimer's disease was 1.8 (95 percent confidence interval, 1.3 to 2.5) per
      increase of 1 SD at base line and 1.6 (95 percent confidence interval, 1.2 to
      2.1) per increase of 1 SD eight years before base line. With a plasma
      homocysteine level greater than 14 micromol per liter, the risk of Alzheimer's
      disease nearly doubled. CONCLUSIONS: An increased plasma homocysteine level is a
      strong, independent risk factor for the development of dementia and Alzheimer's
      disease.

PMID- 11844849
TI  - Clinical outcomes of pulmonary Langerhans'-cell histiocytosis in adults.
AB  - BACKGROUND: Pulmonary Langerhans'-cell histiocytosis is an uncommon interstitial
      lung disease in adults. It has an unpredictable course and may be associated with
      an increased susceptibility to the development of malignant neoplasms. METHODS:
      We reviewed the records of 102 adults with histopathologically confirmed
      pulmonary Langerhans'-cell histiocytosis to ascertain their vital status and
      whether cancer had been diagnosed. The health status of surviving patients was
      quantified with the use of the 36-Item Short-Form General Health Survey. Factors
      potentially associated with survival after the diagnosis of pulmonary Langerhans'
      cell histiocytosis were analyzed with the Cox proportional-hazards model.
      RESULTS: The median follow-up period was 4 years (range, 0 to 23). There were 33
      deaths, 15 of which were attributable to respiratory failure. Six hematologic
      cancers were diagnosed. The overall median survival was 12.5 years, which was
      significantly shorter than that expected for persons of the same sex and calendar
      year of birth (P<0.001). In a univariate analysis, variables predictive of
      shorter survival included an older age (P=0.003), a lower forced expiratory
      volume in one second (FEV1) (P=0.004), a higher residual volume (P=0.007), a
      lower ratio of FEV1 to forced vital capacity (P=0.03), and a reduced carbon
      monoxide diffusing capacity (P=0.001). CONCLUSIONS: The survival of adults with
      pulmonary Langerhans'-cell histiocytosis is shorter than that in the general
      population, and respiratory failure accounts for a substantial proportion of
      deaths among such patients.

PMID- 11844850
TI  - Use of a Staphylococcus aureus conjugate vaccine in patients receiving
      hemodialysis.
AB  - BACKGROUND: In patients with decreased resistance to infection, Staphylococcus
      aureus is a major cause of bacteremia and its complications. The capsular
      polysaccharides are essential for the pathogenesis of and immunity to S. aureus
      infection and are targets for vaccines. METHODS: In a double-blind trial
      involving patients with end-stage renal disease who were receiving hemodialysis,
      we evaluated the safety, immunogenicity, and efficacy of a vaccine with S. aureus
      type 5 and 8 capsular polysaccharides conjugated to nontoxic recombinant
      Pseudomonas aeruginosa exotoxin A. Between April 1998 and August 1999, 1804 adult
      patients at 73 hemodialysis centers were randomly assigned to receive a single
      intramuscular injection of either vaccine or saline. IgG antibodies to S. aureus
      type 5 and 8 capsular polysaccharides were measured for up to two years, and
      episodes of S. aureus bacteremia were recorded. Efficacy was estimated by
      comparing the incidence of S. aureus bacteremia in the patients who received the
      vaccine with the incidence in the control patients. RESULTS: Reactions to the
      vaccine were generally mild to moderate, and most resolved within two days. The
      capsular polysaccharides elicited an antibody response of at least 80 microg per
      milliliter (the estimated minimal level conferring protection) in 80 percent of
      patients for type 5 and in 75 percent of patients for type 8. The efficacy during
      weeks 3 to 54 was only 26 percent (P=0.23). However, between weeks 3 and 40 after
      vaccination, S. aureus bacteremia developed in 11 of 892 patients in the vaccine
      group who could be evaluated for bacteremia, as compared with 26 of 906 patients
      in the control group (estimate of efficacy, 57 percent; 95 percent confidence
      interval, 10 to 81 percent; nominal P=0.02). CONCLUSIONS: In patients receiving
      hemodialysis, a conjugate vaccine can confer partial immunity against S. aureus
      bacteremia for approximately 40 weeks, after which protection wanes as antibody
      levels decrease.

PMID- 11844851
TI  - Images in clinical medicine. An unusual saccular aneurysm.

PMID- 11844853
TI  - Clinical practice. Treatment of tobacco use and dependence.

PMID- 11844852
TI  - Promotion of prescription drugs to consumers.
AB  - BACKGROUND: Spending on prescription drugs is the fastest growing component of
      the health care budget. There is public concern about the possibility that direct
      to-consumer advertising of prescription drugs will result in inappropriate
      prescribing and higher costs of care. Guidelines issued in 1997 by the Food and
      Drug Administration (FDA) regarding advertising to consumers through electronic
      media are considered by some to be responsible for unleashing a flood of direct
      to-consumer advertising. METHODS: Using data on spending for promotional purposes
      and sales of prescription drugs, we examined industrywide trends for various
      types of promotion. We also tracked the relation between promotional efforts and
      sales over time. Finally, we documented the variation in direct-to-consumer
      advertising among and within five therapeutic classes of drugs and compared the
      variation in the intensity of such advertising with variation in the intensity of
      promotion to health care professionals. RESULTS: Annual spending on direct-to
      consumer advertising for prescription drugs tripled between 1996 and 2000, when
      it reached nearly $2.5 billion. Despite this increase, such advertising accounts
      for only 15 percent of the money spent on drug promotion and is highly
      concentrated on a subgroup of products. Within a therapeutic class, there is
      marked variation in the intensity of direct-to-consumer advertising, and the
      amount of such advertising for specific products fluctuates over time. The
      initial surge in direct-to-consumer advertising preceded the 1997 FDA guidelines
      that clarified the rules for electronic direct-to-consumer advertising, and thus
      the 1997 guidelines may not have been the most important reason for the overall
      increase. CONCLUSIONS: Although the use of direct-to-consumer advertising has
      grown disproportionately to other forms of promotion, it continues to account for
      a small proportion of total promotional efforts. Nevertheless, physicians must
      assist patients in evaluating health-related information obtained through direct
      advertising.

PMID- 11844854
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 5-2002. A 15-year-old boy with a retro-orbital mass and impaired
      vision.

PMID- 11844855
TI  - Drug-induced autoimmune red-cell aplasia.

PMID- 11844856
TI  - The consumer and the learned intermediary in health care.

PMID- 11844857
TI  - Direct-to-consumer advertising--education or emotion promotion?

PMID- 11844858
TI  - Direct-to-consumer advertising--strengthening our health care system.

PMID- 11844859
TI  - Direct-to-consumer marketing of high-technology screening tests.

PMID- 11844860
TI  - Bone loss and inhaled glucocorticoids.

PMID- 11844862
TI  - Polymorphisms of the beta2-adrenergic receptor.

PMID- 11844861
TI  - Urinary tract infections and a multidrug-resistant Escherichia coli clonal group.

PMID- 11844863
TI  - B-cell deficiency and type 1 diabetes.

PMID- 11844864
TI  - Cerivastatin and reports of fatal rhabdomyolysis.

PMID- 11844865
TI  - The acts of terrorism.

PMID- 11844866
TI  - War against anthrax.

PMID- 11844867
TI  - Ab initio studies of the reaction of hydrogen transfer from DNA to the
      calicheamicinone diradical.
AB  - BACKGROUND: The biological activity of enediyne chemotherapeutic (anti-cancer)
      agents is attributed to their ability to cleave duplex DNA. Part of the reaction
      of cleavage is the abstraction of hydrogens from the deoxyribose moiety of DNA by
      the biradical formed via a Bergman rearrangement. METHODS: The mechanism of the
      reaction of abstraction of two hydrogen atoms from two deoxyribophosphate
      molecules by the calicheamicinone biradical is studied with ab initio
      calculations at Hartree-Fock and post-Hartree-Fock level. The Titan program is
      used to perform the calculations. RESULTS: It is found that the reactions are
      exothermic and thus thermodynamically reasonable. CONCLUSIONS: The mechanism of
      DNA cleavage by the enediyne-containing drugs is likely to proceed by the
      abstraction of the hydrogens from deoxyribose by the biradical formed by the
      drug. Further studies should determine in which way the modification of the
      drug's structure would make this reaction even more exothermic and, thus, more
      likely to occur.

PMID- 11844868
TI  - Abnormal activation of glial cells in the brains of prion protein-deficient mice
      ectopically expressing prion protein-like protein, PrPLP/Dpl.
AB  - BACKGROUND: Some lines of mice homozygous for a disrupted prion protein gene
      (Prnp), including Ngsk Prnp(0/0) mice, exhibit Purkinje cell degeneration as a
      consequence of the ectopic overexpression of the downstream gene for prion
      protein-like protein (PrPLP/Dpl) in the brain, but others, such as Zrch I
      Prnp(0/0) mice, show neither the neurodegeneration nor the expression of
      PrPLP/Dpl. In the present study, we found that Ngsk Prnp(0/0), but not Zrch I
      Prnp(0/0) mice, developed gliosis involving both astrocytes and microglia in the
      brain. MATERIALS AND METHODS: The brains from wild-type (Prnp(+/+)), Ngsk
      Prnp(0/0), Zrch I Prnp(0/0), and reconstituted Ngsk Prnp(0/0) mice carrying a
      mouse PrP transgene, designated Tg(P) Ngsk Prnp(0/0) mice, were subjected into
      Northern blotting and in situ hybridization using probes of glial fibrillary
      acidic protein (GFAP) and lysozyme M (LM) specific for astrocytes and microglia,
      respectively. Immunohistochemistry was also performed on the brain sections using
      anti-GFAP and anti-F4/80 antibodies. RESULTS: Northern blotting demonstrated
      upregulated expression of the genes for GFAP and LM in the brains of Ngsk
      Prnp(0/0), but not in Zrch I Prnp(0/0) mice. A transgene for normal mouse PrP(C)
      successfully rescued Ngsk Prnp(0/0) mice from the glial activation. In situ
      hybridization and immunohistochemistry revealed activated astrocytes and
      microglia mainly in the white matter of both the forebrains and cerebella. In
      contrast, there was no evidence of neuronal injury except for the Purkinje cell
      degeneration. Moreover, the glial cell activation was notable well before the
      onset of the Purkinje cell degeneration. CONCLUSIONS: These findings strongly
      suggest that ectopic PrPLP/Dpl in the absence of PrP(C) is actively involved in
      the glial-cell activation in the brain.

PMID- 11844869
TI  - ApoE deficiency compromises the blood brain barrier especially after injury.
AB  - BACKGROUND: Apolipoprotein E (apoE) mediates lipoprotein uptake by receptors such
      as the LDL receptor (LDLR). The isoform apoE4 has been linked to Alzheimer's
      disease and to poor outcomes after brain injury. Astrocytes that induce blood
      brain barrier (BBB) properties in endothelium also produce apoE. We decided to
      investigate the role of apoE in BBB function and in the restoration of BBB after
      brain injury. MATERIALS AND METHODS: Wild-type (WT) mice and mice deficient in
      apoE or LDLR were fed normal chow or diets rich in fat and cholesterol. The BBB
      leakage was determined through injection of Evans blue dye and measurement of the
      amount of dye extravasated in the brains 3 hours later. Brain injury was induced
      by applying dry ice directly onto the excised parietal region of the brain. The
      mice were given 7 days to recover. In some experiments, peroxidase was infused to
      observe the site of leakage by histology. RESULTS: We found 70% more spontaneous
      leakage of injected Evans blue dye in the brains of apoE-/- mice than in wild
      type. This increase in permeability appeared selective for the brain. The leaky
      BBB in apoE-/- mice may provide an explanation for the neurological deficits seen
      in these animals. In an established model of BBB leakage induced by trauma (cold
      injury), the apoE-/- mice showed even more compromised BBB function, compared
      with WT mice, suggesting that apoE is important for BBB recovery. No deficit in
      BBB was observed in injured LDLR-/- mice, even on Western Diet. In contrast,
      higher plasma cholesterol levels in apoE-/- mice further increased BBB leakage
      after injury. We extracted 5x more Evans blue from these brains than from WT. In
      the injury model, injection of peroxidase resulted in prominent retention of this
      protein in the cortex of apoE-/- but not in WT. CONCLUSIONS: Our results show
      that the combination of loss of apoE function with high plasma cholesterol and
      especially brain injury results in dramatic BBB defects in the cortex and may
      explain in part the importance of apoE in Alzheimer's disease and in successful
      recovery from brain injury.

PMID- 11844870
TI  - Rho family GTPases regulate mammary epithelium cell growth and metastasis through
      distinguishable pathways.
AB  - BACKGROUND: Relatively few genes have been shown to directly affect the
      metastatic phenotype of breast cancer epithelial cells in vivo. The Rho family of
      proteins, incluing the Rho, Rac and Cdc42 subfamilies, are related to the small
      GTP binding protein Ras and regulated diverse biological processes including gene
      transcription, cytoskeletal organization, cell proliferation and transformation.
      The effects of Cdc42, Rac and Rho on the actin cytoskeleton suggested a possible
      role for Rho proteins in cellular motility and metastasis; however, a formal
      analysis of the role of Rho proteins in breast cancer cellular growth and
      metastasis in vivo had not previously been performed. MATERIALS AND METHODS: We
      generated a panel of MTLn3 rat mammary adenocarcinoma cells that expressed
      similar levels of dominant inhibitory mutants of Cdc42-, Rac- and Rho-dependent
      signaling, to examine the contribution of these GTPases to cell spreading, guided
      chemotaxis, and metastasis in vivo. The ability of Rho proteins to regulate
      intravasation into the peripheral blood was determined by implanting MTLn3 cell
      stable dominant negative lines in nude mice and measuring the formation of breast
      cancer cell colonies grown from the peripheral blood. Serial sectioning of the
      lungs was performed to determine the presence of metastasis in mice in which
      mammary tumors expressing the dominant negative Rho family proteins had grown to
      a similar size. RESULTS: Cell spreading of MTLn3 cells was selectively abrogated
      by N17Rac1. N19RhoA and N17Cdc42 reduced the number of focal contacts (FCs) and
      disrupted the co-localization of vinculin with phosphotyrosine at FCs. While
      N17Rac1 and N17Cdc42 preferentially inhibited colony formation in soft agar, all
      three GTPases affected cell growth in vivo. To distinguish effects on
      tumorigenicity from intravasation into the bloodstream, implanted tumors were
      grown to the same size in nude mice. Each dominant inhibitory Rho protein reduced
      intravasation into the peripheral blood. Lung metastasis of MTLn3 cells was also
      abrogated by the dominant inhibitory Rho proteins, despite the presence of
      residual CFU. CONCLUSIONS: These studies demonstrate for the first time a
      critical role for the Rho GTPases involving independent signaling pathways to
      limit mammary tumor cellular growth and metastasis in vivo.

PMID- 11844871
TI  - Hypertension exacerbates coronary artery disease in transgenic hyperlipidemic
      Dahl salt-sensitive hypertensive rats.
AB  - BACKGROUND: The mechanisms underlying the known interaction of two complex
      polygenic traits, hypertension and hyperlipidemia, resulting in exacerbation of
      coronary artery disease have not been elucidated. Identification of critical
      pathways underlying said exacerbation could identify mechanism-based targets for
      intervention and prevention. MATERIALS AND METHODS: To investigate hypertension-
      atherosclerosis interaction, we studied the inbred transgenic atherosclerosis
      polygenic hypertension Dahl salt-sensitive (S) rat model (Tg53), which over
      expresses human cholesteryl ester transfer protein (hCETP) in the liver, and
      exhibits coronary artery disease and decreased survival compared with control non
      transgenic Dahl S rats. Using serial-section histopathological and
      immunohistochemical analyses, we analyzed the coronary artery disease phenotype
      of Tg53 rats at end-stage marked by cardio-respiratory compromise as the
      experimental equivalent of acute coronary syndromes, and determined the effects
      of reduction of blood pressure through low salt diet (0.008% NaCl) on the
      coronary artery disease phenotype and survival. RESULTS: End-stage Tg53 rats
      exhibit coronary artery lesions in the proximal right coronary artery system
      which exhibit "culprit plaque" features such as plaque inflammation, matrix
      degradation, apoptosis, neovascularization, thrombosis and hemorrhage
      recapitulating said features and heterogeneity of human coronary "culprit
      plaques". Comparative analysis of 6 month vs end-stage lesions reveals distinct
      lesion development profiles of proximal coronary lesions which quickly progress
      from eccentric non-occlusive foam-cell rich lesions at 6 months to occlusive
      "culprit plaques", compared with more distal coronary lesions which exhibit
      occlusive thick-cap atheroma that remain relatively unchanged from 6 months to
      end stage. Reduction of hypertension through a low-salt (0.008% NaCl) diet
      increased survival (P < 0.0001) of Tg53 rats and significantly attenuated the
      coronary artery disease phenotype detected at 10 months of age marked by
      diminished apoptosis, neovascularization, matrix degradation compared with end
      stage lesions detected at <8 months of age. CONCLUSIONS: End stage coronary
      lesions in the Tg53 rats recapitulate many, albeit not all, features of "culprit
      plaques" in humans supporting proposed paradigms of plaque vulnerability
      implicating lesion macrophage enrichment, apoptosis, matrix degradation and
      pathological neovascularization. Comparative time course analysis of coronary
      lesions reveals that plaques which develop into end-stage "culprit plaques" are
      distinct from "stable plaques" by location and early lesion morphology,
      suggesting distinct lesion development and progression pathways. The significant
      effects of low-salt diet-induced decrease in hypertension on right coronary
      disease phenotype provides compelling evidence that polygenic hypertension
      accelerates coronary plaque progression and complication independent of cardiac
      hypertrophy, and more importantly provides paradigmatic support for public health
      policy.

PMID- 11844872
TI  - Deletion pattern of the STS gene in X-linked ichthyosis in a Mexican population.
AB  - BACKGROUND: X-linked ichthyosis (XLI) is an inherited disorder due to steroid
      sulfatase deficiency (STS). Most XLI patients (>90%) have complete deletion of
      the STS gene and flanking sequences. The presence of low copy number repeats
      (G1.3 and CRI-S232) on either side of the STS gene seems to play a role in the
      high frequency of these interstitial deletions. In the present study, we analyzed
      80 Mexican patients with XLI and complete deletion of the STS gene. MATERIALS AND
      METHODS: STS activity was measured in the leukocytes using 7-[(3)H]
      dehydroepiandrosterone sulfate as a substrate. Amplification of the regions
      telomeric-DXS89, DXS996, DXS1139, DXS1130, 5' STS, 3' STS, DXS1131, DXS1133,
      DXS237, DXS1132, DXF22S1, DXS278, DXS1134-centromeric was performed through PCR.
      RESULTS: No STS activity was detected in the XLI patients (0.00 pmoles/mg
      protein/h). We observed 3 different patterns of deletion. The first two groups
      included 25 and 32 patients, respectively, in which homologous sequences were
      involved. These subjects showed the 5' STS deletion at the sequence DXS1139,
      corresponding to the probe CRI-S232A2. The group of 32 patients presented the 3'
      STS rupture site at the sequence DXF22S1 (probe G1.3) and the remaining 25
      patients had the 3' STS breakpoint at the sequence DXS278 (probe CRI-S232B2). The
      third group included 23 patients with the breakpoints at several regions on
      either side of the STS gene. No implication of the homologous sequences were
      observed in this group. CONCLUSION: These data indicate that more complex
      mechanisms, apart from homologous recombination, are occurring in the genesis of
      the breakpoints of the STS gene of XLI Mexican patients.

PMID- 11844873
TI  - In utero exposure to immunosuppressive drugs.
AB  - The number of pregnant women receiving immunosuppressants for anti-rejection
      therapy or autoimmune diseases is increasing. All immunosuppressive drugs cross
      the placenta, raising questions about the long-term outcome of the children
      exposed in utero. There is no higher risk of congenital anomalies. However, an
      increased incidence of prematurity, intrauterine growth retardation (IUGR) and
      generally low birth weight has been reported, as well as maternal hypertension
      and preeclampsia. The most frequent neonatal complications are those associated
      with prematurity and IUGR, as well as adrenal insufficiency with corticosteroids,
      immunological disturbances with azathioprine and cyclosporine, and hyperkalemia
      with tacrolimus. The long-term follow-up of infants exposed to immunosuppressants
      in utero is still limited and experimental studies raise the question whether
      there could be an increased incidence at adult age of some pathologies including
      renal insufficiency, hypertension and diabetes.

PMID- 11844874
TI  - Polychlorinated biphenyls and hexachlorobenzene in full-term neonates. Reference
      values updated.
AB  - OBJECTIVE: To determine actual reference values of polychlorinated biphenyls
      (PCBs) and hexachlorobenzene (HCB) in full-term neonates. PATIENTS AND METHODS:
      Cord blood samples were taken from 200 healthy, full-term neonates in 1998. Blood
      specimens were immediately centrifuged, and serum was stored in glass tubes at 
      20 degrees C up to analysis. Six PCB congeners (IUPAC No. 28, 52, 101, 138, 153,
      and 180) and HCB were determined with capillary gas chromatography with electron
      capture detection. Study groups were tested on mean differences with Wilcoxon's
      test of independent samples. The 95th percentiles by rank were calculated as
      reference values. RESULTS: One sample was excluded from further evaluation
      because of unusually high PCB concentrations. Personal data of the remaining 199
      newborns showed 106 male and 93 female neonates. Mean gestational age was 40
      weeks (range 38-43 weeks), mean birth weight was 3,450 g (2,300-5,060 g). The
      concentrations of the lower-chlorinated PCB congeners 28, 52, and 101 were below
      the detection limit with exception of two probes. Reference values (95th
      percentile by rank) of the higher-chlorinated PCB congeners and HCB were as
      follows: PCB 138, 0.5 microg/l; PCB 153, 0.5 microg/l; PCB 180, 0.4 microg/l; and
      HCB, 0.5 microg/l. CONCLUSIONS: The results of the present study clearly
      demonstrate a further decline in the prenatal uptake of PCBs and HCB since 1994
      1995. During the past 15 years, a 75% decline in the prenatal burden with PCBs
      and a 90% reduction in the burden with HCB could be demonstrated.

PMID- 11844875
TI  - Race, Candida sepsis, and retinopathy of prematurity.
AB  - The objective of this observational cohort study at Georgetown University
      Hospital from January 1, 1994 through December 31, 1997 was to investigate race,
      Candida sepsis, and duration of oxygen exposure in infants with retinopathy of
      prematurity (ROP) with birth weight < or = 1,000 g. The incidence of ROP was
      70.8% (114/161). The incidence of stage III or greater ROP in the Caucasian
      infants was significantly higher at 46.7% (14/30) than in the African-American
      infants at 23.8% (20/84) with p < 0.02. In addition, the incidence of threshold
      disease was higher in Caucasian infants 33.3% (10/30) when compared to African
      American infants 9.5% (8/84) with p < 0.002. Using multiple logistic regression,
      African-American race was found to be an independent protective factor against
      developing severe ROP [adjusted odds ratio 0.39; 95% confidence interval (UCI)
      0.16-0.97]. Extremely-low-birth-weight African-American infants with comparable
      severity of illness (including birth weight, gestational age, duration of
      supplemental oxygen exposure, and Candida sepsis) are less likely to develop
      severe ROP than Caucasian infants.

PMID- 11844876
TI  - Minimal effective dose of indomethacin for the treatment of patent ductus
      arteriosus in preterm infants.
AB  - The aim of this study was to determine if it was possible to decrease the number
      of boluses of indomethacin for the treatment of patent ductus arteriosus. This
      retrospective study included 46 preterm neonates (<34 weeks' GA) who had had an
      ultrasound diagnosis predictive of subsequent symptomatic patent ductus
      arteriosus. All patients had received a daily intravenous doses of indomethacin,
      0.1 mg/kg. Mean age at initiation of treatment was 4.5 +/- 3.1 days. Patency of
      the ductus arteriosus was controlled echocardiographically each day and treatment
      was discontinued as soon as the ductus arteriosus was closed. The initial success
      rate was 84.7%, of which 6.5% reopened. The mean cumulative dose of indomethacin
      was 0.35 mg/kg. There was no correlation between gestational age or birth weight
      and total cumulative dose. Overall tolerance was satisfactory with only one case
      of transient acute renal failure. A weak correlation between the cumulative dose
      of indomethacin and natremia (r = -0.43) or weight gain (r = 0.35) was noted, and
      none with serum creatinine or blood urea nitrogen levels. We confirm that lower
      indomethacin treatment of patent ductus arteriosus in premature neonates are as
      effective as standard protocols.

PMID- 11844877
TI  - Decreased expression of L-selectin on peripheral blood polymorphonuclear
      leukocytes in neonates with severe asphyxia.
AB  - The expression of adherent leukocyte surface molecules, L-selectin (CD62L), and
      Mac-1 (CD11b/CD18) in peripheral blood polymorphonuclear leukocytes (PMNs) was
      studied in 48 neonates and 24 healthy adults using fluorescence flow cytometry. L
      selectin expression was decreased significantly in neonates, especially those
      with severe asphyxia (n = 10) compared with adults. Mac-1 expression was
      significantly increased in neonates compared with adults, but did not differ
      between 24 normal neonates, 14 neonates with mild asphyxia, and 10 neonates with
      severe asphyxia. These results suggest that the magnitude of the decrease in L
      selectin expression reflects the severity of asphyxia in neonates.

PMID- 11844878
TI  - Meconium enhances the release of nitric oxide in human airway epithelial cells.
AB  - Meconium aspiration syndrome (MAS) is a cause of significant morbidity and
      mortality in the perinatal period. Despite the clinical relevance of MAS, its
      pathogenesis is poorly understood and the role played by epithelial-derived
      metabolites not well defined. In this study, we evaluated whether exposure to
      meconium affects the release of nitric oxide production in human airway
      epithelial cells. Monolayers of A549 cells, a transformed human epithelial cell
      line, were incubated with various concentrations of meconium. Control cells were
      incubated with serum-free medium in a similar manner. The supernatant fluid was
      removed at various time points and assayed for nitrite production. In selected
      experiments, the effects of dexamethasone (10(-6) M), L-nitroarginine methyl
      ester (L-NAME, 10(-6) M) and indomethacin (10(-6) M) on nitrite release were
      evaluated. Results were obtained in terms of pmol/mg protein and expressed as %
      control (mean +/- SE). We found exposure to meconium produced a significant
      release of nitrite from A549 cells. Dexamethasone, L-NAME and indomethacin
      inhibited meconium-induced release of nitrite. Our findings demonstrate meconium
      enhances the production of nitric oxide from A549 cells suggesting that airway
      epithelial cells and their metabolic products may play an important role in the
      pathogenesis of MAS.

PMID- 11844879
TI  - A low serum sICAM-1 level may assist in the exclusion of neonatal infection.
AB  - Serum levels of soluble intercellular adhesion molecule-1 (sICAM-1) in 46 samples
      from 46 infants undergoing intensive care were studied. Residual serum remaining
      after routine electrolyte analysis was utilised. sICAM-1 levels were determined
      by ELISA. Blind retrospective chart review was employed to determine whether
      infants were infected. Serum levels were significantly elevated in infants with
      proven and probable infection, compared with non-infected infants (p < 0.001).
      sICAM-1 levels in serum were comparable to levels previously established in
      plasma samples. The results suggest that serum sICAM-1 measurement is a simple
      and robust test that differentiates infected from non-infected infants and that a
      low level of serum sICAM-1 may particularly assist in the exclusion of infection.

PMID- 11844880
TI  - Plasma and urine elastase alpha-1-proteinase inhibitor levels in neonatal urinary
      tract infection.
AB  - OBJECTIVE: To examine whether plasma or urine elastase alpha(1)-proteinase
      inhibitor (E-alpha(1)-PI) levels could be used as a diagnostic marker of urinary
      tract infection (UTI) in neonates. SUBJECTS AND METHODS: Plasma and urine E
      alpha(1)-PI levels were measured by immunoassay in 23 neonates with UTI at the
      time of admission and 72 h after the onset of treatment and in 10 'normal'
      neonates (i.e. with trivial problems). Additionally E-alpha(1)-PI plasma levels
      were measured in 15 neonates with septicemia. RESULTS: E-alpha(1)-PI plasma
      levels did not differ between normal neonates and those with UTI. Urine E
      alpha(1)-PI levels were significantly higher in neonates with UTI on admission
      compared to normal neonates. A significant decrease in urine E-alpha(1)-PI levels
      was noticed 72 h after the onset of treatment in all but 2 neonates in whom
      infection persisted. In this study, we have found that the urine E-alpha(1)-PI
      concentration at a cutoff level of 48 microg/l had a sensitivity of 83%, a
      specificity of 90%, a positive predictive value of 95% and a negative predictive
      value of 69% for the diagnosis of neonatal UTI. CONCLUSION: Elevated levels of E
      alpha(1)-PI in urine seem to be a useful tool for the diagnosis of UTI in
      neonates (even in those that have already been started on antibiotics) and
      possibly a valuable marker for early recognition of treatment failure.

PMID- 11844881
TI  - The development of a circadian pattern of salivary cortisol secretion in the
      neonatal piglet.
AB  - Saliva was collected from neonatal piglets in order to assess the secretory
      dynamics of cortisol in the newborn piglet. Saliva was collected from two litters
      of piglets (n = 16) from multiparous sows at 07.00, 11.00, 15.00 and 19.00 h on
      days 0, 1, 2, 4, 6, 10, 14, 18, 22, 26 and 30 post partum. Salivary cortisol
      concentration was determined by radioimmunoassay. Salivary cortisol concentration
      was high perinatally and declined with age. The frequency of escape attempts and
      vocalisation intensity during collection, as well as the similarity in salivary
      cortisol concentration on day 22 in control piglets and piglets that had provided
      samples repeatedly from day 0 suggested that this was not an adaptive response. A
      circadian pattern was evident in female pigs from day 6, whereas males displayed
      a similar pattern from day 10. The collection of saliva in the piglet provides a
      viable alternative to blood sampling for the assessment of a glucocorticoid
      circadian rhythm.

PMID- 11844882
TI  - Prolonged apneas and hypoxia mediated by nicotine and endotoxin in piglets.
AB  - OBJECTIVE: Infections and maternal smoking are risk factors for SIDS, and toxins
      from common bacteria have been proposed as a causative link between infections
      and SIDS. Nicotine can be transferred in significant amounts postnatally to the
      infant through environmental tobacco smoke or maternal smoking before nursing. We
      investigated the acute effects of nicotine and endotoxin on repeated apnea by
      laryngeal reflex stimulation and the following autoresuscitation. DESIGN: Thirty
      four 1-week-old (+/- 1 day) piglets were sedated and randomized to 1 of 4
      pretreatment groups: (1) 1 microg endotoxin i.v./kg; (2) 5 microg nicotine
      i.v./kg; (3) 1 microg endotoxin i.v./kg and 5 microg nicotine i.v./kg, and (4)
      placebo. Apnea was induced by insufflation of 0.1 ml of acidified saline (pH 2)
      in the subglottic space of the trachea three times with intervals of 2 min.
      RESULTS: Pretreatment with endotoxin caused a significant increase in plasma TNF
      alpha in the endotoxin groups (mean value +/- SEM 953 +/- 246 and 980 +/- 226
      pg/ml, respectively) but no significant change in plasma IL-1 beta. Blood
      pressure, respiratory rate or S(a)O(2) was not significantly affected before
      induced apnea. Both pretreatment with nicotine and endotoxin caused prolonged
      apneas by 35-45%, a complete loss of normal hyperventilation during
      autoresuscitation, and prolonged hypoxia after apnea. CONCLUSIONS: Nicotine and
      endotoxin interferes with autoresuscitation after apnea. This experimental model
      on piglets may shed light over important mechanisms involved in the causation of
      SIDS.

PMID- 11844883
TI  - Comparison of effects of perflubron and surfactant lung lavage on pulmonary gas
      exchange in a piglet model of meconium aspiration.
AB  - In a piglet model of meconium aspiration we compared lavage with surfactant with
      that with perflubron (PFOB) and a control group. A human meconium suspension was
      instilled into piglets which were randomized in 3 (n = 6 each) groups. After lung
      injury, the control group was ventilated with high-frequency oscillatory
      ventilation (HFOV) without suctioning and lavage. A second group was lavaged with
      10 ml/kg diluted surfactant, a third with 10 ml/kg pre-oxygenated PFOB.
      Thereafter, the animals of both groups were ventilated with HFOV. After lung
      injury by instillation of meconium, no further improvement in oxygenation was
      possible in animals of the control group and 3 piglets died during the
      ventilation. The subjects of the surfactant group improved promptly, and at the
      end of the study the arterial pO(2) was significantly better than immediately
      after injury as compared with the other groups. Lavage with PFOB had intermediate
      effects in gas exchange and oxygenation compared to surfactant lavage. No
      differences were observed in arterial blood pressure and heart rate as well as in
      histological lung injury score between all groups. Lavage with exogenous
      surfactant as well as with PFOB improve pulmonary gas exchange in a piglet model
      of meconium aspiration.

PMID- 11844884
TI  - Oxytocin treatment during early life influences reproductive performance in ad
      libitum fed and food-restricted female rats.
AB  - Oxytocin treatment may permanently alter endocrine axes resulting in anti-stress
      and anabolic effects. However, the nutritional status influences the effects of
      oxytocin. The specific aims of this study were to investigate the effects of
      postnatal oxytocin treatment on reproductive performance in adult life, by
      studying maternal weight gain, adiposity, plasma levels of IGF-I as well as fetal
      and placental weights in the following groups of animals: (1) Ad libitum fed dams
      coming from ad libitum fed mothers. (2) Ad libitum fed dams coming from food
      restricted mothers. (3) Food-restricted dams coming from ad libitum fed mothers.
      (4) Food-restricted dams coming from food-restricted mothers. Oxytocin treatment
      postnatally had long-term effects and increased adiposity in pregnant dams and
      stimulated placental and fetal growth relative to saline-treated dams. However,
      if the dams themselves had been exposed to food restriction during fetal life,
      the effect of postnatal oxytocin treatment changed. The oxytocin-treated mothers
      were still fatter but had smaller fetuses. In conclusion, postnatal oxytocin
      treatment influences reproductive performance in later life but is dependent on
      the mother's previous and current nutritional experience.

PMID- 11844885
TI  - Ontogeny of endothelin-converting enzyme gene expression and protein content in
      the ovine fetal lung.
AB  - Endothelin 1 (ET-1) is a potent vasoconstrictor and smooth muscle comitogen that
      is produced by endothelin-converting enzyme 1 (ECE-1) in endothelium and smooth
      muscle of the vascular wall in adult pulmonary arteries. However, little is known
      about the role of ECE-1 in the fetal pulmonary circulation. The ET-1 protein
      content falls just prior to birth in the fetal lamb lung. We hypothesized that
      the expression of ECE-1 is developmentally regulated and that ECE-1 levels fall
      prior to birth. To test this hypothesis, we measured lung ECE-1 mRNA levels and
      protein content and determined the cellular localization of ECE-1 expression in
      lung tissues from fetal lambs between 70 and 140 days of gestation (term = 145
      days), newborn lambs, and ewes. We found that ECE-1 mRNA expression and protein
      content were lower in the fetal lamb lung just prior to birth in comparison with
      the newborn lamb lung. Immunolocalization of ECE-1 protein showed expression of
      ECE-1 in the vascular endothelium but not in the vascular smooth muscle at all
      gestational ages. We conclude that ECE-1 is developmentally regulated and that
      ECE-1 is expressed in the vascular endothelium but not in the smooth muscle of
      the fetal pulmonary vasculature. We speculate that alterations in ECE-1
      contribute to the changes in ET-1 levels during the perinatal period and that the
      majority of ET-1 produced in the fetal lamb pulmonary vasculature is produced by
      the vascular endothelium.

PMID- 11844887
TI  - Efficacy of olanzapine in the treatment of psychosis in dementia with lewy
      bodies.
AB  - OBJECTIVE: This study sought to determine whether patients with dementia with
      Lewy bodies (DLB) and psychosis responded to treatment with olanzapine. METHODS:
      This was a post hoc analysis of a subgroup of patients with DLB included in a
      larger double-blind, placebo-controlled, randomized parallel group trial of
      olanzapine for the treatment of psychosis in patients with Alzheimer's disease.
      Patients meeting the consensus criteria for DLB and exhibiting parkinsonism and
      visual hallucinations were selected from the initial study. Psychosis was
      assessed with the Neuropsychiatric Inventory/Nursing Home (NPI-NH) version and
      the Brief Psychiatric Rating Scale (BPRS). Extrapyramidal symptoms were evaluated
      with the Simpson-Angus scale. RESULTS: Twenty-nine patients met the criteria for
      DLB; 10 were randomized to placebo, 5 received 5 mg of olanzapine, 7 received 10
      mg of olanzapine and 7 received 15 mg of olanzapine. Patients with DLB treated
      with 5 mg of olanzapine showed significant reductions in delusions and
      hallucinations. Patients treated with 10 mg showed a significant reduction in the
      NPI-NH delusion subscale score. No significant differences were found between the
      15-mg group and the placebo group. Confirmatory findings emerged from an analysis
      of the BPRS. Caregivers reported decreased disruptions in their occupational
      routines for the group receiving 5 or 10 mg of olanzapine. There was no
      significant exacerbation of parkinsonian symptoms in any study group, no
      decrement in Mini-Mental State Examination scores in any of the treatment groups,
      and symptoms suggestive of anticholinergic toxicity did not differ among
      treatment groups. CONCLUSIONS: This preliminary analysis suggests that olanzapine
      (5 or 10 mg) reduces psychosis in patients with DLB without worsening
      parkinsonism.

PMID- 11844888
TI  - Increased levels of adrenocortical and gonadal hormones in mild to moderate
      Alzheimer's disease.
AB  - Hormonal changes during normal aging include decreasing levels of gonadal
      hormones and adrenal androgens. These hormones influence multiple nervous
      functions, including cognition and mood. Related to this, abnormalities at
      several levels of the hypothalamic-pituitary-adrenal axis (HPA) have been
      reported in patients with Alzheimer's disease (AD). We studied steroid hormones
      in 33 patients with mild to moderate AD (12 men; 21 women, 76.4 +/- 7.8 years)
      and 22 healthy elderly controls (10 men; 12 women, 75.4 +/- 7.5 years old,
      respectively). Basal levels of serum cortisol, dehydroepiandrosterone (DHEA) and
      androstenedione were significantly increased in AD patients. Women with AD had
      significantly higher levels of DHEA and androstenedione. Serum estradiol levels
      were non-significantly increased in women with AD. After adjustment for age and
      BMI women with AD had significantly increased levels of androstenedione and DHEA.
      Increased gonadal hormone levels in mild to moderate AD may reflect an increased
      secretion, and/or alterations in metabolism of these hormones. This may influence
      the symptomatology and progression of the disease.

PMID- 11844886
TI  - The disablement process: a conceptual framework for dementia-associated
      disability.
AB  - Most of the social and economic burden of dementia is attributable to its
      consequences in terms of disability. In this review, we describe the concepts
      defined in the disablement process model of Verbrugge and Jette [Soc Sci Med
      1994;38:1-14] and show how they apply to dementia. The main pathway leads from
      pathology to impairments, functional limitations and disability. Pathologies (any
      cause of dementia) are expressed by impairments in specific cognitive processes.
      Functional limitations are limitations in generic cognitive tasks such as
      remembering a list of words or orientating oneself in time and space. They are
      responsible for disability in activities of daily living. Predisposing risk
      factors as well as introduced intraindividual and extraindividual factors speed
      up or slow down the main pathway. We show how the model can help in understanding
      the functional consequences of dementia, for better assessment and management of
      demented subjects.

PMID- 11844890
TI  - Association analysis for the genetic variants of the NMDA receptor subunit 2b and
      Alzheimer's disease.
AB  - N-methyl-D-aspartate (NMDA) receptor dysfunction has been implicated in the
      pathogenesis of Alzheimer's disease (AD). The NMDA receptor is composed of
      several subunits, of which the receptor 2b subunit (NR2b) is of particular
      significance for AD. Abundant in the hippocampus of normal subjects, reductions
      in NR2b have been demonstrated in the hippocampus and entorhinal cortex of AD
      patients. In this study, we tested the hypothesis that the allelic variant
      (C2664T) of the NR2b confers susceptibility to AD using a sample population of
      132 AD patients and 114 normal controls. The distribution of the NR2b genotypes
      (p = 0.600) and alleles (p = 0.652) did not differ significantly between AD
      patients and controls, however, suggesting that it is unlikely that the NR2b
      C2664T polymorphism plays a substantial role in conferring susceptibility to AD.
      We propose that other genetic variations of the NMDA subunits, relating either to
      AD or to the therapeutic response for NMDA partial agonists, may need further
      investigation.

PMID- 11844889
TI  - Corticobasal degeneration and frontotemporal dementia presentations in a kindred
      with nonspecific histopathology.
AB  - We report the clinical, neuropsychological, electroencephalographic and
      radiologic findings in a kindred with varying clinical presentations of a
      neurodegenerative disorder. Postmortem examination of one member with clinically
      suspected corticobasal degeneration (CBD) revealed nonspecific histopathology
      maximally involving the frontoparietal cortex with negligible degenerative
      changes in the basal ganglia and substantia nigra. The findings in this and other
      kindreds demonstrate that (1) similar findings on ancillary testing can occur in
      relatives presumably suffering from the same pathophysiologic process despite
      dissimilar clinical presentations, (2) the 'CBD syndrome' is not specific for
      CBD, (3) extrapyramidal dysfunction can exist in the absence of appreciable basal
      ganglia and nigral degeneration, (4) nonspecific histopathology can underlie
      familial focal/asymmetric cortical degeneration syndromes and (5) many of the
      findings in CBD are comparable to those reported in frontotemporal dementia.

PMID- 11844891
TI  - Factorial validation of the Severe Impairment Battery for patients with
      Alzheimer's disease. A pilot study.
AB  - The Severe Impairment Battery (SIB) estimates the cognitive aptitudes and other
      skills of severely impaired dementia patients. The main objective of this pilot
      study was to clearly identify the number of factors present in the SIB and to
      analyze the relationships between the different cognitive domains explored by the
      SIB and loss of autonomy. We administered the SIB, the Mini Mental State
      Examination (MMSE) and two scales of dependency to 48 patients with Alzheimer's
      disease in its late stages. A factorial analysis (Principal Components Analysis)
      showed a 4-factor solution for the SIB: a cognitive factor, a praxis and
      visuospatial functions factor, the reactivity to external stimuli factor and the
      social aptitudes factor. A factorial analysis involving the dependency scales
      showed a cognitive factor, a dependency and constructional praxis factor, the
      reactivity to external stimuli factor and the social aptitudes factor. Reactivity
      to external stimuli and social aptitudes were not significantly correlated to
      cognitive aspects nor to dependency. The finding of dependency as a factor
      different from cognitive deterioration suggests that, in setting a treatment
      strategy for demented patients, attempts should be made to treat dependency in
      its own right. In addition, since reactivity to external stimuli and social
      aptitudes are not related to cognitive aspects nor to dependency, these functions
      should also be encouraged and stimulated.

PMID- 11844892
TI  - Frontal impairment in subcortical ischemic vascular dementia in comparison to
      Alzheimer's disease.
AB  - We compared the performance of patients with Alzheimer's disease to that of
      patients with subcortical vascular dementia (s-IVD) in a set of tasks assessing
      categorization abilities, sustained and selective attention, and set-shifting and
      set-maintaining skills. Only the measures of naming and categorization abilities
      on the Test of Classification and Recall of Pictures (TCRP) proved useful in
      differentiating AD from s-IVD patients. s-IVD patients showed worse performance
      than AD on the TCRP categorization measures, while both AD and s-IVD patients
      were equally impaired in other tasks assessing executive functions (EF). With
      respect to the naming task, s-IVD patients made significantly more perseverative
      and unrelated errors than AD patients. Moreover, in the s-IVD group, we found a
      strong correlation between categorization ability and an attentional test score
      (Attentional Matrices), while no such correlation emerged in the AD group. These
      results suggest a dissociated impairment of EF in the 2 dementia groups. In our
      view, the lack of inhibition and the inability to manipulate complex information
      are responsible for a greater executive dysfunction in s-IVD patients in
      comparison with AD patients. The capacity to build up strategies appears more
      preserved in AD patients, whose impaired performance in executive tasks seems to
      be related to an impairment of attentional shifting and working memory.

PMID- 11844893
TI  - Decreased CSF-beta-amyloid 42 in Alzheimer's disease and amyotrophic lateral
      sclerosis may reflect mismetabolism of beta-amyloid induced by disparate
      mechanisms.
AB  - Both tau and beta-amyloid 42 (Abeta42) have been implicated in Alzheimer's
      disease (AD) and tau alone in frontotemporal dementia (FTD) and amyotrophic
      lateral sclerosis (ALS). These proteins can be measured in the cerebrospinal
      fluid (CSF); differences from normal CSF levels may reflect pathophysiological
      mechanisms. Using ELISAs, we investigated the levels of total CSF-tau (here
      referred to as tau), phosphorylated CSF-tau (phosphotau), and Abeta42 in patients
      with AD (n = 19), FTD (n = 14), ALS (n = 11) and Parkinson's disease (PD; n = 15)
      and in age-matched controls (n = 17). Both CSF-tau and CSF-phosphotau were
      increased in AD compared with FTD (p < 0.001), ALS (p < 0.001), PD (p < 0.001)
      and controls (p < 0.001). CSF-Abeta42 was markedly decreased in AD and ALS (both
      p < 0.001) and slightly decreased in FTD (p < 0.01) and PD (p < 0.05) compared
      with controls. Using CSF-phosphotau may improve the differentiation of AD from
      FTD and ALS in clinical praxis. Furthermore, decreased CSF-Abeta42 levels may be
      common in neurodegenerative disorders possibly reflecting changes in the
      metabolism of beta-amyloid or axonal degeneration.

PMID- 11844894
TI  - Psychotic symptoms and emotional distress in patients with Guillain-Barre
      syndrome.
AB  - Psychological disturbances in 49 most severely compromised Guillain-Barre
      syndrome patients were prospectively studied by a semistructured interview and
      assessed by repeat psychiatric examination during the patients' stay in the neuro
      intensive care unit (ICU). Additional information was obtained from attending
      physicians, nurses and relatives. Anxiety (82%), acute stress disorder,
      depressive episodes (67%) and brief reactive psychosis (25%) were observed, with
      oneiroid psychosis (14%) among the latter. Psychotic episodes were strongly
      associated (p < 0.001) with severe tetraparesis, artificial ventilation and
      multiple cranial nerve dysfunction. CSF protein concentration was also correlated
      with the occurrence of psychotic symptoms. Patients themselves experienced loss
      of communication to be the most difficult condition to cope with. Fifty-five
      percent explicitly felt reassured by the environment of the ICU and 90% described
      contact with relatives to be most helpful. Our data suggest that motor
      deprivation and loss of communication are the conditions most closely connected
      with the occurrence of psychotic symptoms. Therapeutically, continuous
      psychosocial support and psychopharmacological measures may both be valuable
      tools to ameliorate distress.

PMID- 11844895
TI  - A longitudinal cardiovascular autonomic function study in mild Guillain-Barre
      syndrome.
AB  - To identify subclinical autonomic dysfunction in mild Guillain-Barre syndrome
      (GBS), a set of autonomic function tests was serially performed for up to 6
      months in 5 GBS patients with mild disability at the nadir. Parasympathetic
      autonomic function tests consisted of Valsalva ratio and R-R interval variation
      during rest and deep breathing. Sympathetic autonomic function was evaluated by
      blood pressure responses to sustained handgrip, hand immersion in ice water, and
      active standing. The results showed that abnormal parasympathetic and sympathetic
      function was frequently encountered in all 5 patients during the acute stage of
      the illness. Autonomic dysfunction occurred both in axonal and demyelinating
      types of GBS. There was a trend of improvement in most autonomic function tests
      after 3 months, comparable to the recovery of motor function. In conclusion,
      subclinical autonomic dysfunction was present in mild GBS. It was temporary and
      would resolve spontaneously.

PMID- 11844896
TI  - Loss of postural reflexes in long-term occupational solvent exposure.
AB  - Inhalation of organic solvents has long been known to damage various nervous
      systems, including cerebellum, brainstem, and pyramidal tract. However, little is
      known about the damage of the dopaminergic system. We report two patients with
      occupational long-term solvent exposure who developed postural instability
      without other features of parkinsonism. The concentration of HVA in CSF was
      decreased and the retropulsion was dramatically improved after the administration
      of levodopa. These findings indicate that the nigrostriatal dopaminergic neurons
      were disturbed by chronic solvent exposure, resulting in the loss of postural
      reflexes.

PMID- 11844897
TI  - Zolmitriptan versus a combination of acetylsalicylic acid and metoclopramide in
      the acute oral treatment of migraine: a double-blind, randomised, three-attack
      study.
AB  - This multicentre, randomised, double-blind study compared oral zolmitriptan 2.5
      mg with a combination of oral acetylsalicylic acid 900 mg and metoclopramide 10
      mg as acute anti-migraine therapy for 3 migraine attacks. In total, 666 patients
      took at least one dose of study medication (326 took zolmitriptan and 340 took
      acetylsalicylic acid plus metoclopramide). The percentage of patients with a 2
      hour headache response after the first dose for all 3 attacks (the primary end
      point) was 33.4% with zolmitriptan and 32.9% with acetylsalicylic acid plus
      metoclopramide [odds ratio 1.06, 95% confidence interval (CI) 0.77-1.47; p =
      0.7228]. For the majority of secondary end points, the two treatments
      demonstrated comparable efficacy. However, post hoc analysis showed that
      significantly more patients receiving zolmitriptan were free of pain 2 h after
      the first dose in all 3 attacks compared with patients receiving acetylsalicylic
      acid plus metoclopramide (10.7 vs. 5.3%; odds ratio 2.19, 95% CI 1.23-4.03; p =
      0.0095). In addition, post hoc analysis showed that the overall 2-hour pain-free
      response rate was consistently higher with zolmitriptan (34.6%) than with
      acetylsalicylic acid plus metoclopramide (27.9%) (odds ratio 1.40, 95% CI 1.09
      1.78; p = 0.007). Both treatments reduced migraine-associated nausea, vomiting,
      phonophobia and photophobia. There were no important inter-group differences with
      respect to the onset of meaningful migraine relief, the frequency of headache
      recurrence, the usage or efficacy of a second dose of medication or the use of
      escape medication. However, at the last attack, the proportion of patients who
      expressed overall satisfaction with the treatment was significantly higher in the
      zolmitriptan group, i.e. 83.7%, versus 75.0% with acetylsalicylic acid plus
      metoclopramide (p = 0.0346). Both agents were well tolerated. Adverse events were
      reported by 40.8% (133/326) of zolmitriptan-treated patients and 29.1% (99/340)
      of those treated with acetylsalicylic acid plus metoclopramide. The incidence of
      withdrawals due to adverse events was very low with both zolmitriptan (0.9%) and
      the combination regimen (1.5%); the latter percentage included 1 patient who
      withdrew from the study due to phlebitis, which was classified as a serious
      adverse event. This study showed that zolmitriptan is effective and well
      tolerated for the acute treatment of moderate to severe migraine. Zolmitriptan
      was at least as effective as acetylsalicylic acid plus metoclopramide in
      achieving a 2-hour headache response, but significantly more effective than the
      combination therapy for other end points, including the 2-hour pain-free
      response.

PMID- 11844898
TI  - Efficacy, tolerability and safety of oral eletriptan and ergotamine plus caffeine
      (Cafergot) in the acute treatment of migraine: a multicentre, randomised, double
      blind, placebo-controlled comparison.
AB  - The 5-HT(1B/1D/1F) agonist eletriptan, at an oral dose of 80 mg, has been shown
      to be more efficacious than sumatriptan 100 mg and placebo in the treatment of
      migraine attacks with or without aura. Another commonly prescribed oral treatment
      for migraine attacks is Cafergot (1 mg ergotamine tartrate with 100 mg caffeine
      per tablet). The efficacy, tolerability and safety of 40- and 80-mg doses of
      eletriptan and 2 tablets of Cafergot were compared in a double-blind, randomised,
      placebo-controlled, parallel-group trial involving 733 migraine patients.
      Patients recorded symptoms at baseline (before treatment) and 1, 2, 4 and 24 h
      after dosing. Headache intensity was assessed on a 4-point scale (3 = severe
      pain, 2 = moderate pain, 1 = mild pain, 0 = no pain). Significantly more
      eletriptan-treated patients (80 mg, 68%; 40 mg, 54%) than Cafergot-treated
      patients (33%; p < 0.001) reported headache response (improvement from moderate
      to-severe to mild or no pain) at 2 h. Substantially more eletriptan recipients
      reported no pain (80 mg, 38%; 40 mg, 28%; Cafergot, 10%; placebo, 5%; p < 0.001).
      Eletriptan headache response rates at 1 h were significantly higher (80 mg, 39%;
      40 mg, 29%; Cafergot, 13%; placebo, 13%; p < 0.002 for each comparison). Both
      doses of eletriptan were significantly more effective than Cafergot in reducing
      nausea (p < 0.0001), photophobia (80 mg, p < 0.0001; 40 mg, p < 0.002),
      phonophobia (80 mg, p < 0.0001; 40 mg, p < 0.003) and functional impairment (p <
      or = 0.001) at 2 h. Adverse events were generally mild or moderate and transient.
      This randomised trial shows that oral eletriptan is more efficacious in the acute
      treatment of migraine than oral Cafergot and is well tolerated.

PMID- 11844899
TI  - New insights into the viral theory of amyotrophic lateral sclerosis: study on the
      possible role of Kaposi's sarcoma-associated virus/human herpesvirus 8.
AB  - In the last few years, three new herpesviruses, HHV-6, -7 and -8, have been
      discovered, which share interesting biological characteristics for a possible
      role in the development of both neurological and lymphoproliferative diseases. In
      particular HHV-8, besides being strongly associated with Kaposi's sarcoma, is
      related with several lymphoproliferative diseases. More recently, specific viral
      sequences belonging to HHV-8 have been detected in autoptic brain specimens from
      multiple sclerosis patients and controls, suggesting that, similarly to HHV-6,
      this novel herpesvirus is strongly neurotropic. HHV-8 is an unusual herpesvirus
      in that it is able to produce homologues of several human gene products,
      resulting in alterations in cell cycle, in apoptosis and cell-mediated immune
      responses. To verify a possible relationship between HHV-8 and the development of
      amyotrophic lateral sclerosis (ALS), we investigated the presence of signs of HHV
      8 infection, by both nested polymerase chain reaction (nPCR) and indirect immune
      fluorescence analysis in ALS patients. Both PCR and serological data did not
      suggest a clear role of this virus in originating ALS. Nevertheless, new insights
      into the mechanisms by which viruses may interact with the host cell genome and
      with the human immune system make the viral hypothesis of ALS still worthy of
      further studies.

PMID- 11844900
TI  - Downregulation of striatal dopamine D2 receptors in advanced Parkinson's disease
      contributes to the development of motor fluctuation.
AB  - The purpose of this study was to evaluate the contribution of the postsynaptic
      mechanism to the development of motor fluctuation in advanced Parkinson's disease
      (PD). We used 123I-iodobenzamide single-photon emission computed tomography to
      measure the striatal dopamine D2 receptor densities in early levodopa-naive PD,
      chronic PD with stable levodopa response, and advanced PD with fluctuating
      levodopa response. The basal ganglia/frontal cortex ratios at both hemispheres
      were calculated and averaged. PD patients with fluctuating levodopa response
      showed a significant decrease in striatal dopamine D2 receptor densities compared
      to those with early (1.57+/- 0.20 vs. 1.77 +/- 0.12, p = 0.009) or chronic stable
      PD (1.57 +/- 0.20 vs. 1.77 +/- 0.10, p = 0.024). We conclude that the decreased
      D2 receptor densities in advanced PD reduced the 'safety factor' for synaptic
      transmission and contributed to the development of motor fluctuation.

PMID- 11844901
TI  - Antibody-induced botulinum toxin therapy failure: can it be overcome by increased
      botulinum toxin doses?
AB  - In some patients treated with botulinum toxin type A (BT) therapy failure occurs
      due to the formation of antibodies against BT (BT-AB). We investigated whether
      increased BT doses can overcome this form of therapy failure. Eight patients with
      cervical dystonia, secondary BT therapy failure and evidence of BT-AB formation
      in the mouse diaphragm bioassay received BT test doses (Dysport, Ipsen Ltd.,
      Maidenhead, Berks, UK) into one of their sternocleidomastoid muscles. Test doses
      were increased in three steps at 3-month intervals and their effect on the
      amplitude of the electromyographic activity of the sternocleidomastoid muscle
      under maximal isometric activation (M-EMG) was measured and compared to a control
      group. In step 1 (200 or 300 MU) the M-EMG reduction was 12 +/- 13% compared to
      85 +/- 10% (200 MU) and 83 +/- 9% (300 MU) in the control group. In step 2 (400,
      600 or 800 MU) the M-EMG reduction was 25 +/- 21% compared to 78 +/- 7% (400 MU)
      in the control group. In step 3 (1,600 or 1,800 MU) the M-EMG reduction was 24
      plus minus 10%. Side effects were not observed in any of the patients studied. In
      1 patient with partial secondary BT therapy failure, with a low BT-AB titre
      (0.0015 U/ml) and with a moderately pathological M-EMG reduction of 40% with 200
      MU a normal M-EMG reduction of 71% could be regained with 800 MU. In three
      subsequent therapeutic injection series with quadrupled BT doses in all target
      muscles the original therapy outcome could be regained and maintained. Side
      effects or increasing BT-AB titres were not observed. Even massively increased BT
      doses cannot overcome BT-AB-induced complete secondary therapy failure. However,
      in patients with partial secondary therapy failure, low BT-AB titres and a
      moderately pathological M-EMG reduction, increased BT doses might regain and
      maintain normal BT efficacy without induction of side effects or increasing BT-AB
      titres.

PMID- 11844902
TI  - Pallidal deep brain stimulation in a parkinsonian patient with late-life
      dementia: sustained benefit in motor symptoms but not in functional disability.

PMID- 11844903
TI  - Cutaneous mucinoses complicating interferon beta-1b therapy.

PMID- 11844904
TI  - Cavernous sinus syndrome secondary to tuberculous meningitis.

PMID- 11844905
TI  - Wernicke's encephalopathy in a patient with multiple symmetrical lipomatosis and
      the A8344G mutation of mitochondrial DNA.

PMID- 11844906
TI  - Spinocerebellar ataxia type 2 (SCA2) associated with retinal pigmentary
      degeneration.

PMID- 11844907
TI  - Gestational age at intrauterine myelomeningocele repair does not influence the
      risk of prematurity.
AB  - OBJECTIVE: To determine the effect of gestational age at the time of intrauterine
      myelomeningocele repair on the duration of pregnancy and the gestational age at
      the time of delivery. METHODS: This study is a retrospective chart review of the
      maternal and neonatal medical records of all infants undergoing intrauterine
      myelomeningocele repair at Vanderbilt University Medical Center. Birth weight,
      gestational age at the time of surgery and gestational age at the time of
      delivery were recorded. Infants were divided into 2 groups depending on
      gestational age at the time of surgery, either > or = 25 weeks' gestation (group
      1) or < 25 weeks (group 2). Results were expressed as medians and interquartile
      ranges. Statistical analysis was done using the unpaired (2-sample) t test; p
      values < or = 0.05 were considered significant. RESULTS: Ninety-five infants were
      studied. Fifty-one infants were repaired after 25 weeks' gestation (group 1) at a
      median gestational age of 26.3 weeks (range 25.6-27.6). Their median gestational
      age at delivery was 34.4 weeks (range 32.6-35.3). Forty-four infants were
      repaired before 25 weeks' gestation (group 2). Surgery was done at a median
      gestational age of 23.6 weeks (range 22.4-24.5). The median gestational age at
      delivery was 34 weeks (range 31.6-35.3; p = 0.88). CONCLUSION: Early intrauterine
      myelomeningocele repair before 25 week's gestation does not decrease the
      gestational age at delivery when compared with repair after 25 weeks.

PMID- 11844908
TI  - Effects of urinary trypsin inhibitor in patients at risk for premature labor with
      a bulging fetal membrane.
AB  - OBJECTIVE: To investigate the effect of urinary trypsin inhibitor (UTI) in
      patients at risk for premature labor with bulging membrane. METHODS: Patients who
      had developed a bulging membrane from 22 to 27 weeks and 6 days of gestation were
      studied. These cases were divided into two types based on the severity: those
      with a moderately developed bulging membrane like a 'dome' (dome type), and those
      with a membrane prolapsed into the vagina, resulting in an 'hourglass' shape
      (hourglass type). We compared the outcomes of treatment with or without UTI (UTI
      group versus non-UTI group) in each type. Gestational age at delivery, birth
      weight, prolongation time from admission to delivery, and neonatal mortality rate
      were examined in each group. RESULTS: A total of 43 patients with a bulging
      membrane were analyzed. In 21 patients with the dome type, gestational age at
      delivery (the UTI group versus the non-UTI group; 30.4 +/- 5.0 versus 26.4 +/-
      1.9 weeks, p < 0.05), birth weight (1,436.8 +/- 708.3 versus 882.8 +/- 261.6 g, p
      < 0.05) and neonatal mortality rate (0/13 versus 3/8, p < 0.05) were all
      significantly improved by the use of UTI. On the other hand, in 22 patients with
      the hourglass type, there was no significant difference between the UTI group and
      the non-UTI group. The overall prevalence of histological chorioamnionitis was
      60%. CONCLUSION: These results suggest that UTI therapy is very effective in
      patients at risk for premature labor with a moderately developed bulging membrane
      during the second trimester.

PMID- 11844909
TI  - Fetal atrial flutter recorded prenatally by magnetocardiography.
AB  - A case of fetal atrial flutter successfully recorded by magnetocardiography (MCG)
      is reported. Initial ultrasonography revealed frequent fetal atrial extrasystoles
      at 31 weeks of gestation. Fetal MCG was recorded using a multichannel MCG system
      at 31, 35 and 38 weeks of gestation. A series of fluctuations in the baseline of
      the MCG were noted at 35 and 38 weeks of gestation, which were revealed to be
      atrial flutter P waves. The averaged MCG showed that the fetal arrhythmia was an
      atrial flutter with a 3:1 atrioventricular block. The diagnosis was confirmed by
      neonatal electrocardiogram. Fetal MCG may be useful for the diagnosis of fetal
      atrial flutter.

PMID- 11844910
TI  - Relationship between meconium staining and amniotic fluid volume in term
      pregnancies.
AB  - OBJECTIVE: Our purpose was to evaluate the relationship between meconium-stained
      amniotic fluid (MEC-AF) and amniotic fluid volume (AFV) and their impact on the
      risk of cesarean delivery for fetal indications in term pregnancies. METHODS:
      1,655 live-born singleton gestations delivering at > or = 37 weeks within 7 days
      of sonographic assessment of the amniotic fluid index (AFI) were studied. AFI was
      categorized as: oligohydramnios (< or = 5.0 cm); decreased (5.1-8.0 cm); normal
      (8.1-18.0 cm); increased (18.1-23.9 cm), and polyhydramnios (> or = 24.0 cm).
      Frequencies of MEC-AF for each AFV category were stratified by gestational age
      (GA) and rates of cesarean delivery for fetal indications compared between
      patients with clear amniotic fluid and those with MEC-AF. Stepwise logistic
      regression analyses were performed for determinants of MEC-AF and the need for
      cesarean delivery for fetal indications. RESULTS: The frequency of MEC-AF at
      birth in term pregnancies was not related to AFV: oligohydramnios (16.7%);
      decreased (16.7%); normal (20.1%); increased (24.4%), and polyhydramnios (22.1%).
      The only factor associated with the occurrence of MEC-AF was increasing GA at
      delivery (p < 0.01). Both MEC-AF (p < 0.02) and decreasing neonatal ponderal
      index (p < 0.02) were independently associated with cesarean delivery for fetal
      distress. CONCLUSIONS: MEC-AF does not appear to be related to AFV in term
      pregnancies, and its presence increases the risk of cesarean delivery for fetal
      distress independent of AFV and neonatal ponderal index.

PMID- 11844911
TI  - Fetal cell isolation from maternal blood cultures by flow cytometric hemoglobin
      profiles. Results of a preliminary clinical trial.
AB  - OBJECTIVE: We conducted a trial to test if the blood of pregnant women contains
      fetal clonogenic erythroid cells the progeny of which can be identified and
      isolated by a newly developed flow-sorting procedure. METHODS: We have previously
      demonstrated the identification of fetal nucleated red cells in cocultures of
      fetal and adult blood. The procedure is based on profiles of the correlated
      contents of fetal and adult hemoglobin (HbF and HbA, respectively), using
      antibodies specific for the different hemoglobin chains. In such profiles, fetal
      cells contain only HbF, while the vast majority of adult cells contain either
      only HbA or a combination of HbA and HbF. HbF+ HbA- cells are flow sorted and
      fetal cells identified by fluorescence in situ hybridization, using chromosome
      specific probes. This technique provides a yield that approaches 100%, meaning
      that fetal cells will be found even if the culture contains only a single fetal
      erythroid colony among thousands of maternal colonies. Peripheral blood samples
      were obtained from 11 women carrying chromosomally normal male fetuses, from 5
      women carrying trisomy 21 fetuses, and from 2 women carrying trisomy 18 fetuses.
      A further six samples came from women with an unknown fetal karyotype. As
      positive controls, we used blood samples drawn after termination procedures that
      tended to induce some fetomaternal hemorrhage. In parallel to the method being
      tested, we employed alternative techniques of fetal cell detection: one third of
      the mononuclear cell preparations from each maternal blood sample was not
      cultured but labeled with anti-HbF antibodies for flow sorting of F+ cells. Ten
      percent of the total harvested cell population of each culture was subjected to
      quantitative polymerase chain reaction analysis targeting a Y-chromosome-specific
      sequence. RESULTS: Most post-termination blood samples yielded fetal cells with
      high purity which demonstrates the validity of the method. However, no fetal
      cells were found in any of the maternal blood samples with normal or abnormal
      pregnancies, neither before nor after culture. CONCLUSION: We conclude that a
      cell culture approach targeting clonogenic erythroid cells offers no advantage
      over established methods of direct isolation.

PMID- 11844912
TI  - Evaluation of a culture system for enrichment of CD34+ hematopoietic progenitor
      cells present in maternal blood.
AB  - BACKGROUND: Clonogenic expansion of fetal cells in maternal blood is one approach
      to overcome the very low number of target cells available for prenatal genetic
      analysis. However, efficient methods of enrichment, culturing conditions and
      subsequent analysis of fetal cells are lacking. Optimization of this technique
      requires more detailed evaluation of the composition and distribution of fetal
      cells that cross the placenta into the maternal circulation. Previous studies by
      others have shown that fetal blood is rich in CD34+ progenitor cells capable of
      expansion in cultures supplemented with hematopoeitic growth factors. Moreover,
      CD34+ fetal cells have been recovered from maternal blood following enrichment.
      OBJECTIVE: In this study, we examine the type and frequency of hematopoietic
      progenitor cells detected in maternal (n = 13) and non-pregnant control (n = 4)
      peripheral blood specimens. METHODS: A methylcellulose-based culture system was
      used to perform colony assays on CD34+-enriched or non-enriched cells. Overall, a
      total of 2,249 colonies were scored for colony type among the 17 samples. To
      determine whether fetal cells were present and expanded, all colonies present in
      each of the 10 confirmed male-cases (n = 1,525 colonies) were examined either by
      PCR or FISH. RESULTS: With CD34+-enriched maternal samples, we observed a
      significantly higher number of burst-forming unit-erythroid (BFU-E) and a reduced
      number of colony-forming unit-granulocyte, macrophage (CFU-GM) colonies compared
      to the non-enriched samples. Of 1,067 colonies analyzed by PCR for the amelogenin
      locus on X and Y, none were found positive for the 250-bp Y-specific sequences.
      Of 458 colonies tested by FISH for presence of X and Y probe signals, no XY-male
      cells were detected. CONCLUSION: We conclude that hematopoiesis is enhanced
      during pregnancy, but the number of fetal progenitor cells is either very low or
      fail to expand using the enrichment techniques and culturing conditions described
      in this study. Further development of methods is warranted before considering
      this approach for prenatal diagnosis.

PMID- 11844914
TI  - Myomectomy as a pregnancy-preserving option in the carefully selected patient.
AB  - OBJECTIVES: To present the indications for myomectomy during pregnancy and to
      discuss complications possibly related and unrelated to the procedure. METHOD AND
      RESULTS: A 33-year-old patient at 18 weeks of gestation underwent removal of a
      1,570-gram symptomatic fundic myoma. Histologically the patient had a
      leiomyomatous neoplasm of uncertain malignant potential. The pregnancy was
      continued under sequential observation with magnetic resonance imaging and
      ultrasound. At 36 weeks of gestation a healthy girl with an upper extremity limb
      defect was born via cesarean section. Follow-up of the mother and the child was
      uneventful. CONCLUSIONS: Certain known risk factors in pregnant women with myomas
      can predispose to complications during pregnancy. Women with such risk factors or
      women who have failed medical therapy should be offered the option of undergoing
      myomectomy as a pregnancy-preserving procedure.

PMID- 11844913
TI  - Inability to clonally expand fetal progenitors from maternal blood.
AB  - OBJECTIVES: To confirm the recent report of the culture of single clones of fetal
      progenitor cells from maternal blood. METHODS: Hemopoietic progenitor cells were
      cultured from 16 blood samples obtained from women pregnant with a male singleton
      fetus. Single colonies were isolated by micro-manipulation and examined by
      multiplex real-time PCR. RESULTS: Of a total of 1,674 colonies examined, 1,648
      were identified as being maternal. No colonies were detected of fetal origin.
      CONCLUSIONS: The clonal expansion of single fetal colonies from the maternal
      circulation is not feasible by current methods.

PMID- 11844915
TI  - In vitro studies of haematopoietic colony-forming capacity of human fetal liver
      cells at exposure to cytotoxic and immunomodulatory drugs.
AB  - OBJECTIVE: Intrauterine transplantation with haematopoietic stem cells (SC) as a
      treatment for immunological, haematological and metabolic inherited disorders has
      not been effective in fetuses with a normal immunological status. Inhibition of
      the fetal haematopoiesis or immunosuppression might therefore be a therapeutic
      alternative in fetal SC transplantation. The aim of the present study was to
      evaluate the effects of drugs that might be considered as therapeutic options in
      fetal transplantations on the colony-forming capacity of fetal haematopoietic SC.
      METHODS: Fetal liver cells were incubated with doxorubicin, daunorubicin,
      antithymocyte-globulin (ATG), OKT-3 (Orthoclone) and betamethasone. The effects
      of these drugs on colony formation by fetal hematopoietic SC were evaluated.
      Colony-forming capacity assays were cultured during 10 days after drug incubation
      on day 1 and evaluated for differences in number of colonies compared to
      unexposed cells. For betamethasone, similar studies were performed with adult
      bone marrow. RESULTS: A significant reduction in fetal liver haematopoietic
      colony formation of BFU-E, CFU-GM and CFU- GEMM was detected when 0.1 M
      doxorubicin (p < 0.05) and 0.5 microM daunorubicin (p < 0.05) were added. OKT-3
      (5 microg/ml) and ATG (4 microg/ml) significantly reduced BFU-E, CFU-GM and CFU
      GEMM (p < 0.05). A concentration of 0.2 microg/ml betamethasone caused a
      significant reduction of BFU-E, CFU-GM and CFU-GEMM (p < 0.05). CONCLUSIONS: The
      drugs investigated in this in vitro study were capable to different degrees to
      decrease the colony-forming capacity of fetal haematopoietic progenitor cells.
      Whether this strategy will become an alternative in fetal SC transplantations is
      an open question and further studies are required to elucidate the potential use
      of these drugs in fetal transplantation.

PMID- 11844916
TI  - Effect of pathological perinatal conditions on the maternofetal transfer of
      mononuclear cells.
AB  - OBJECTIVE: It is known that mononuclear cells can cross the placenta in both
      directions: from mother to fetus and the other way. In addition, it has been
      shown that perinatal pathological conditions can affect the fetomaternal cell
      transfer. This study has focused on the question whether perinatal conditions
      will also support the transfer of maternal cells in the fetus. METHODS:
      Minisatellite polymerase chain reaction (PCR) with a sensitivity of 1:100 was
      used to examine blood samples of 36 mother-child pairs for transplacental
      mononuclear cell transfer (group 1). Furthermore, 28 blood samples of mother
      child pairs were examined by allele-specific PCR (sensitivity 1:1,000) for
      maternofetal mononuclear cell transfer; only 9 of these mother-child pairs were
      informative (group 2). RESULTS: Three cases of maternofetal and 2 additional
      cases of fetomaternal mononuclear cell transfer could be documented in group 1; 2
      of the 9 informative samples in group 2 showed a maternofetal mononuclear cell
      transfer. In conclusion, 9 of 40 cases lacking maternofetal cell transfer and 4
      of 5 cases with maternofetal cell transfer were high-risk deliveries (p < 0.01).
      CONCLUSION: The current study shows that certain ante-partum conditions like
      placental insufficiency or chorioamnionitis increase significantly the chance
      that maternal cells enter the fetus.

PMID- 11844917
TI  - Prenatal diagnosis of L1 cell adhesion molecule mutations. Capabilities and
      limitations.
AB  - OBJECTIVE: Discuss the capability for and limitations of prenatal detection of L1
      cell adhesion molecule (L1CAM) mutations. METHODS: Haplotype analysis by PCR and
      PAGE. Mutation detection by SSCP, followed by dideoxy sequencing. Confirmation of
      sequencing results with PCR and NcoI digestion. RESULTS: A 1-bp deletion was
      found in exon 2 of L1CAM in all affected males and obligate carriers in the
      pedigree. Prenatal detection is now possible for subsequent pregnancies.
      CONCLUSION: In a large gene with widespread mutations such as L1CAM, a mutation
      must be detected in another family member before direct prenatal mutation testing
      can be done within the required timeframe. If the proper family members are
      available, haplotyping offers a fast but indirect test with several limitations.

PMID- 11844919
TI  - Sepsis due to Clostridium perfringens after pregnancy termination with feticide
      by cordocentesis: a case report.
AB  - We report a case of sepsis due to Clostridium perfringens after termination of
      pregnancy at 22 weeks with feticide by cordocentesis. Three weeks earlier, the 41
      year-old patient had undergone an amniocentesis and a full trisomy 13 karyotype
      had been discovered. Feticide was performed by injection of thiopental and
      potassium chloride after percutaneous umbilical foetal blood sampling through the
      same needle. The patient delivered vaginally with signs of chorioamnionitis and
      septicaemia. She recovered under broad-spectrum antibiotherapy. C. perfringens
      was present in maternal blood cultures, placental smears and foetal organs. We
      discuss the possible mechanisms of infection by C. perfringens, including
      inoculation of intestinal germs.

PMID- 11844918
TI  - Prenatal ultrasound may predict fetal response to therapy in non-hydropic fetuses
      with supraventricular tachycardia.
AB  - OBJECTIVE: To study the fetal response to prenatal therapy in non-hydropic
      fetuses with supraventricular tachycardia (SVT) as a function of fetal
      haemodynamic status at presentation. STUDY DESIGN: Retrospective study. MATERIAL
      AND METHODS: Between 1990 and 2000, 40 non-hydropic fetuses presented with SVT.
      Twenty-eight had reciprocating SVT and 12 had atrial flutter. Ten fetuses had
      significant tricuspid valve regurgitation. All fetuses were treated prenatally.
      The main outcome measurement was fetal response to therapy as assessed by the
      rate of prenatal SVT reduction and by the mean time interval to sinus rhythm
      restoration. RESULTS: The mean gestational age at presentation was 29 +/- 4.9
      weeks. Overall, there were 39 live births and 1 intrauterine death. Reduction of
      SVT was achieved prenatally in 32 cases (80%). Among the 30 cases without
      tricuspid regurgitation, prenatal conversion to sinus rhythm was achieved in 27
      cases (90%) with a mean time interval of 7 days. Among the 10 fetuses presenting
      with tricuspid regurgitation, the rate of prenatal conversion was significantly
      lower (5/10) and the mean time interval to conversion was significantly longer
      (24 days; p = 0.04, Mann-Whitney test). In the subgroup treated by digoxin as
      first-line therapy (n = 32), the interval to sinus rhythm restoration was also
      significantly higher in the presence of tricuspid regurgitation, with a slightly
      but not significantly lower reduction rate. CONCLUSION: The response to prenatal
      therapy may be poorer in cases presenting with tricuspid regurgitation.

PMID- 11844920
TI  - Association of homozygous alpha-thalassaemia of the Southeast Asian type with
      hypospadias: still an intriguing enigma.

PMID- 11844921
TI  - On understanding ageing: design and inferences.

PMID- 11844922
TI  - The interpretation of shared age-related variance among factors in cross
      sectional cognitive aging studies.
AB  - Many cross-sectional correlational studies in cognitive aging have focused on
      explaining age-related variance. It has been assumed that variables sharing
      variance with both cognition and age may be the key explanatory variables
      underlying the cognitive decline in normal aging. Statistical biases intrinsic to
      this approach have been described by Hofer and Sliwinski and a narrow age cohort
      design proposed. The present paper aims at explaining how Hofer and Sliwinski's
      criticisms apply to a specific type of research design in cognitive aging where
      the goal is to identify underlying aging processes, but does not apply to more
      general gerontological research. Methods to estimate bias in cross-sectional
      studies are required as is greater awareness of this potential bias.

PMID- 11844923
TI  - Age is not necessarily aging: another step towards understanding the "clocks"
      that time aging.
AB  - Hofer and Sliwinski raise a critical concern regarding a popular practice in
      aging research of inferring associations among aging changes of different
      processes from correlations based on cross-sectional age differences. It is shown
      analytically that cross-sectional information drawn from age-heterogeneous
      samples is not suitable for answering questions about the interdependence between
      aging changes. While in general we agree with the problem pointed out by Hofer
      and Sliwinski, the two aims of this commentary are: (1) to highlight links
      between the specific concern and two long-standing issues confronting life-span
      researchers and (2) to introduce alternative approaches that are currently
      underutilized in gerontological research. We elaborate general issues with
      respect to challenges in inferring aging changes from age differences and using
      age as a proxy for aging. We show that several other sources of variance
      independent of rates of change, such as cohort- and mortality-related selection
      effects, are confounded in age-heterogeneous designs. We suggest general
      considerations for developing more explicit theories of cognitive aging in the
      future. Alternative research methods and paradigms for studying the causes and
      mechanisms of the aging mind at different time scales and levels are also
      highlighted. The role of chronological age in aging research is rather
      "superficial". To understand the underlying processes and mechanisms of cognitive
      aging, classical process-oriented, rather than solely age-oriented, theoretical
      conceptions need to be reconsidered and reified with new methodological and
      empirical advances. Concerted gerontological research endeavors utilizing recent
      progresses made in statistical analyses of dynamic processes and in cognitive and
      computational neurosciences that may lead to fruitful breakthroughs.

PMID- 11844924
TI  - Correct identification and explanation of age-related changes are always
      possible.
AB  - In this commentary, it is argued that the definition of the time or the age
      variable in the models presented by Hofer and Sliwinski is ambiguous, and a
      standard interpretation of this time of age variable is proposed instead. Some
      simulation studies are presented, the results of which indicate that, even with
      age-heterogeneous cross-sectional data, correct identification of the true
      sources of age-dependent variation is possible. An important qualification, based
      on new methodological work in progress, is given of the scope of longitudinal
      designs. It is concluded that all kinds of age-related changes are potentially
      interesting and can be correctly identified and explained.

PMID- 11844925
TI  - An examination of the Hofer and Sliwinski evaluation.
AB  - Although we fully endorse the thesis of Hofer and Sliwinski that all research
      designs and analytical procedures should be critically examined before accepting
      conclusions based upon them, in this commentary we question whether their
      critical examination is complete. In particular, we suggest that they neglected
      some disadvantages of longitudinal and narrow age range cross-sectional designs
      and that they may have been overly pessimistic with respect to the potential
      usefulness of cross-sectional designs for certain research questions.

PMID- 11844927
TI  - Uncertainties in the pharmacotherapy of Parkinson's disease and how to solve
      them.
AB  - The causative relationship between levodopa and the long-term motor complications
      of therapy, along with the possibility that levodopa may be toxic to dopaminergic
      neurones in vivo, has led to a move away from its use in early Parkinson's
      disease. Alternatives such as amantadine and the anticholinergics suffer from
      poor efficacy in comparison and a high side effect profile. Selegiline is
      probably less effective than levodopa and the issue of its safety versus
      neuroprotective properties remains unresolved. Long-term trials with the old and
      newer dopamine agonists as monotherapy have shown that as a class they can delay
      the development of dyskinesia and probably response fluctuations. However, major
      uncertainties remain about their use as monotherapy in all patients instead of
      levodopa. No data on their effect on quality of life and health care costs are
      available. Most of the trials were heavily biased towards younger patients with
      Parkinson's disease, so little data in the elderly are available. In later
      disease when patients have already developed motor complications on levodopa, the
      choice rests between adjuvant therapy with a dopamine agonist, a catechol-O
      methyltransferase inhibitor (COMT; e.g. entacapone), and a monoamine oxidase B
      inhibitor (MAO B; e.g. selegiline). Trials with the former two classes have
      confirmed that they can reduce 'off' time, reduce levodopa dose, and improve
      motor impairments and disabilities with acceptable increases in adverse events
      including dyskinesia. Trials with selegiline as adjuvant therapy were less
      rigorous but it can allow a reduction in levodopa dose and motor impairments. No
      studies have compared these three classes of drug as adjuvant therapy so there is
      no evidence on which to base rational decisions in this type of patient. A large
      pragmatic trial which includes older patients is needed to clarify which
      treatment is best for different stages of the disease.

PMID- 11844928
TI  - Age-related effect of aluminium on the catalase activities of the brains of two
      species of poikilothermic vertebrates.
AB  - BACKGROUND: Although aluminium (Al) has been implicated in various
      neuropathological states with aging due to its involvement in neurotoxicity, the
      exact role of the metal ion is still unclear. OBJECTIVE: The aim of the present
      study is to ascertain whether the antioxidant enzymes of the brain protecting
      from oxidative damages which accumulate with aging are regulated by Al in an age
      dependent manner. METHOD: The inhibitory effect of Al on the catalase activity of
      brain homogenates of two species of poikilothermic vertebrates was studied in
      vitro using a spectrophotometric method. RESULTS: At a final concentration of 666
      microM, the metal ion inhibited the enzyme activity of the brain in both species.
      In fish brain the degree of inhibition was not age-dependent. On the other hand,
      the rate of inhibition increased between young and middle-aged lizards followed
      by a decline in the old counterparts. CONCLUSION: Al inhibits catalase activity
      but this effect may not be a major contributing factor in the aging of the brain
      in the two species capable of maintaining their antioxidant capacity until old
      age.

PMID- 11844929
TI  - Alterations of sensory perceptions in healthy elderly subjects during fasting and
      refeeding. A pilot study.
AB  - BACKGROUND: Sensory perception losses may contribute to age-related malnutrition
      by affecting food selection and consumption. OBJECTIVE: To determine the effects
      of a 36-hour fast followed by a 6-hour refeeding period on sensory perceptions in
      7 healthy elderly subjects (65-80 years of age) and 6 healthy young subjects (18
      35 years of age). METHODS: Self-perceived hunger and olfactory ratings were
      recorded on visual analogue scales in response to three different classes of
      odorant stimuli (salt, sweet and sour). Odorant stimuli were administered three
      times during the study, twice during the fasting period (12 and 24 h fasted) and
      once at the end of the re-nutrition period. RESULTS: A significant difference was
      found between the two groups for the self-perceived hunger ratings in response to
      the sour stimuli. A significant difference was observed between the two groups
      for olfactory ratings as regards the salt and sour odorant stimuli. Among the
      metabolic changes associated with fasting and refeeding, blood glucose was
      significantly related (r(2) = 0.97, p = 0.001) to the perception of hunger in the
      control group subjects, but no such relationship was found for the elderly
      subjects (r(2) = 0.16, p = NS). CONCLUSION: (1) Self-perceived hunger and
      olfactory ratings are specifically affected in healthy elderly. (2) Nutritional
      status can modulate sensory perceptions in elderly and young during the
      transition from fasting to refeeding.

PMID- 11844930
TI  - Non-compliance with drug treatment and reading difficulties with regard to
      prescription labelling among seniors.
AB  - BACKGROUND; The link between experiencing difficulties in reading or
      understanding and non-compliance with drug treatment among seniors is not clearly
      established. OBJECTIVES: We measured the effect of both difficulties in reading,
      as well as difficulties in understanding prescription labelling, on non
      compliance with drug treatments among seniors. Since the use of a pill organizer
      prepared by a pharmacist may compensate for the problems in reading, we also
      checked the potential modifying effect of the use of a pill organizer on these
      two associations. METHOD: Data on non-compliance with drug treatment,
      comprehension of prescription labelling and on the factors potentially linked to
      non-compliance, were collected during face-to-face interviews with 325 seniors.
      RESULTS: In all, 126 respondents (38.8%) were not able to read all the
      prescription labels and 218 (67.1%) did not fully understand all the information.
      153 respondents were non-compliant with their drug treatment. After adjusting for
      sex, age, living alone or not, having had help with taking the medication, use of
      a pill organizer, having had sufficient funds to procure his medicine during the
      previous month, belief in the efficacy of his medication, perception of his state
      of health, satisfaction with physician-given and pharmacist-given information, as
      well as the complexity of the treatment, the two associations remained
      statistically non-significant. The use of a pill organizer was not a modifying
      factor. CONCLUSION: Our results did not demonstrate the existence, among seniors,
      of an association between non-compliance and difficulty in reading and
      understanding prescription labelling.

PMID- 11844931
TI  - What diseases of the eyes affected biblical men? A review of age-associated
      visual impairment.
AB  - BACKGROUND/OBJECTIVE: The elderly have suffered from visual impairment for
      thousands of years. This report evaluates the first documented cases of visual
      disability in the elderly as described in the Bible. RESULTS: Three old men
      suffered from a gradual loss of vision. It is more likely that either mature
      cataract, or age-related macular degeneration, or asymptomatic open-angle
      glaucoma, or ischemic optic neuropathy or optic nerve atrophy were associated
      with visual loss. Corneal ulceration or scarring can also be considered.
      Hereditary causes of optic nerve atrophy and retinal degeneration can be
      excluded. CONCLUSION: This report demonstrates that the roots of contemporary
      modern gerontology lead back to biblical times.

PMID- 11844933
TI  - Inward remodeling follows chronic vasoconstriction in isolated resistance
      arteries.
AB  - The hypothesis was tested that chronic vasoconstriction is followed by a
      structural reduction in lumen diameter, measured at full dilation. An in vitro
      model of pressurized rat skeletal muscle arterioles was used. During a 3-day
      experimental period, constriction of active vessels was achieved with fetal calf
      serum or endothelin-1 (ET-1). Maximal dilation revealed inward remodeling from
      179 +/- 6.5 microm lumen diameter on day 0 to 151 +/- 6.3 microm on day 3 at 75
      mm Hg in vessels incubated with serum (n = 8). Similarly, ET-1 induced inward
      remodeling from 182 +/- 5.2 to 164 +/- 3.7 microm (n = 6). When constriction
      during organoid culture was inhibited with papaverin or verapamil, inward
      remodeling was fully prevented: 184 +/- 6.3 to 184 +/- 5.8 microm for papaverin
      (n = 6) and 174 +/- 5.5 to 177 +/- 7.4 microm for verapamil (n = 6). A chronic
      reduction in diameter without tone was achieved in vessels that were kept at a
      low pressure (2-5 mm Hg; n = 6). Here, no remodeling was found, thereby ruling
      out that a chronic reduction in diameter alone is sufficient for inward
      remodeling. These data show that a persistent active reduction in lumen diameter
      is followed by inward remodeling of arterioles.

PMID- 11844932
TI  - Noradrenaline-induced paxillin phosphorylation, ERK activation and MEK-regulated
      contraction in intact rat mesenteric arteries.
AB  - In rat mesenteric arteries, noradrenaline (NA) induces a time-dependent increase
      in tyrosine phosphorylation of a number of proteins, one of which was identified
      as paxillin. NA-induced protein tyrosine phosphorylation was ablated by tyrosine
      kinase inhibition, virtually unaffected by protein kinase C (PKC) inhibition or
      PKC downregulation and was mimicked by KCl. NA also caused a time-dependent
      activation of the extracellular signal-regulated kinases (ERK)1 and ERK2. These
      responses were blocked by the ERK-activating kinase (MEK) inhibitor PD98059 and
      by tyrosine kinase inhibition but only modestly attenuated by PKC downregulation
      or inhibition. Pretreatment of cannulated mesenteric arteries (50 mm Hg internal
      pressure) with PD98059 significantly reduced the contractile responsiveness of
      the vessels to NA (1.56 +/- 0.14 microM, EC(50) control; 3.32 +/- 0.49 microM,
      EC(50) + PD98059, p < 0.01). Thus, NA induces time-dependent increases in protein
      tyrosine phosphorylation and ERK activation in rat mesenteric arteries that could
      suggest a role for Ca(2+)-dependent non-receptor tyrosine kinases and ERKs in the
      response of small arteries to NA. In addition, the modulation of NA-induced
      mesenteric artery contraction by inhibition of the MEK/ERK pathway further
      implicates ERK in the regulation of, though perhaps not the mediation of NA
      induced small artery contraction.

PMID- 11844934
TI  - Detection of hemodynamic turbulence in experimental stenosis: an in vivo study in
      the rat carotid artery.
AB  - In a previous study, we have demonstrated that turbulences in arteries less than
      1.5 mm in diameter perfused ex vivo by an oscillated flow can be determined using
      nonlinear mathematical models. The hypothesis tested here was that nonlinear
      analyses enable the in vivo detection of turbulences in blood flow in vessels
      with dimensions affected by microsurgery. Twenty Wistar male rats were studied.
      After an intraperitoneal anesthesia (50 mg/kg sodium pentobarbital), each right
      carotid artery was dissected and a transit time flowmeter was used to measure
      blood flow. Arteries were studied in control conditions and graded stenoses,
      which were performed by a collar system and progressively increased from 0 to
      95%. For each flow signal, time delay, false-nearest neighbors, correlation
      dimension and the largest Lyapunov exponent were computed to characterize the
      level of turbulence. The level of turbulence was highly correlated with the
      degree of stenosis induced (p < 0.001). The correlation dimensions of all the
      flow signals varied between 3 and 5, thus implying that more than three
      independent noninteger control variables were necessary to account for the
      complexity of rat carotid artery dynamics. Turbulence flow significantly
      increased in arteries with 40-95% stenosis. Nonlinear analysis may be useful to
      determine the turbulence level of an in vivo flow in arteries less than 1.5 mm in
      diameter and might be clinical useful for turbulence detection after
      microsurgery.

PMID- 11844935
TI  - Correlation of pulmonary arterial smooth muscle structure and reactivity during
      adaptation to extrauterine life.
AB  - Peripheral pulmonary arteries remodel immediately after birth as pulmonary
      vascular resistance falls. We hypothesised that there is a link between the
      response to agonist stimulation and wall structure in early postnatal life.
      Arteries from fetal, newborn and 14-day-old piglets were mounted on a perfusion
      myograph. Lumen diameter and smooth muscle cell nuclear positions were recorded
      after sequential addition of KCl, U46619 and bradykinin. Subsequently, vessels
      were studied by confocal and transmission electron microscopy. Contractile
      agonist stimulation caused a greater and faster reduction in lumen diameter in
      the newborn than at 14 days (p < 0.02) and the distance between cells decreased
      more in the newborn (p < 0.05). Unstimulated smooth muscle cells changed shape
      from being rounded in the fetus to fusiform by 14 days, with increasing
      length/width ratio (p < 0.01). On contraction, length/width ratio decreased most
      at 14 days (p < 0.01). Extracellular matrix, collagen and elastin, sparse at
      birth, increased by 14 days. Thus a greater change in lumen diameter in relation
      to cellular contraction was observed in the newborn than at 14 days and the
      amount of extracellular matrix within the vessel wall may affect the overall
      change in lumen diameter.

PMID- 11844936
TI  - Effect of a high salt diet on microvascular antioxidant enzymes.
AB  - High dietary salt intake decreases the endothelium-dependent dilation of skeletal
      muscle arterioles by inhibiting local nitric oxide (NO) activity without changing
      vascular smooth muscle responsiveness to NO. Under these conditions,
      microvascular walls show evidence of oxidative stress, and scavengers of reactive
      oxygen species (ROS) abolish this oxidative stress and restore normal arteriolar
      responses to acetylcholine (ACh). We tested the hypothesis that the salt
      dependent appearance of microvascular ROS, and accompanying reduction in
      endothelium-dependent dilation, is due to a decrease in antioxidant enzyme
      expression or activity. We studied spinotrapezius muscle microvessels in rats fed
      normal (NS) (0.45%) or high (HS) (7%) salt diets for 4-5 weeks. Western analysis
      of arteriolar and venular protein showed no difference between groups in the
      content of superoxide dismutase (Cu/Zn SOD), catalase, or glutathione peroxidase.
      The catalase inhibitor 3-amino-1,2,4-triazole (3AT) increased arteriolar and
      venular oxidant activity (assessed by tetranitroblue tetrazolium reduction) by
      the same amount in both groups, suggesting similar levels of catalase activity.
      3AT did not affect arteriolar responses to ACh in either group. The Cu/Zn SOD
      inhibitor diethyldithiocarbamate increased arteriolar and venular oxidant
      activity to a lesser extent in HS rats, suggesting reduced Cu/Zn SOD activity in
      this group. Cu/Zn SOD inhibition decreased arteriolar responses to ACh only in NS
      rats. These findings suggest that endogenous Cu/Zn SOD preserves the endothelium
      dependent control of arteriolar tone in NS rats, and that a reduction in Cu/Zn
      SOD activity contributes to the loss of arteriolar NO activity in HS rats.

PMID- 11844937
TI  - Met-RANTES inhibition of mucosal perfusion failure in acute intestinal transplant
      rejection - role of endothelial cell-leukocyte interaction.
AB  - Acute rejection-induced microvascular injury results in graft dysfunction,
      ultimately leading to graft loss. Infiltration of T cells and monocytes as a
      consequence of an enhanced endothelial cell-leukocyte interaction appears to play
      an important role in this deleterious process. Recruitment of these pro
      inflammatory cells to the vessel wall is mediated by chemokines such as RANTES.
      Heterotopic small bowel transplantation was performed in rats with the fully
      allogeneic Brown Norway-Lewis strain combination and, as a control, the syngeneic
      Lewis-Lewis strain combination. Intravital microscopy was performed from
      postoperative day 1-7 in both groups. The percentages of perfused villi and
      villus stasis, mucosal and muscular functional capillary densities, red blood
      cell velocities, and finally, firm adherence of leukocytes in postcapillary
      submucosal venules were assessed. Syngeneic small bowel transplantation revealed
      homogeneous perfusion of villi and muscle layers over the whole study period.
      Allogeneic small bowel transplantation showed a decline in perfusion from
      postoperative day 1 until complete failure on postoperative day 7. This was
      accompanied by a continuous increase in endothelial cell-leukocyte interaction
      which reached a plateau on postoperative day 5. Met-RANTES treatment at 200
      microg/day for 5 days markedly attenuated both the decrease in functional
      capillary density and the increased endothelial cell-leukocyte interaction in
      rats following allogeneic small bowel transplantation. We conclude that blocking
      chemokine receptors, thereby limiting endothelial cell-leukocyte interaction, may
      constitute a useful therapeutic approach to the prevention of microcirculatory
      perfusion failure in acute transplant rejection.

PMID- 11844938
TI  - Current-induced vasodilation during water iontophoresis (5 min, 0.10 mA) is
      delayed from current onset and involves aspirin sensitive mechanisms.
AB  - Study of the microcirculation by iontophoresis is potentially confounded by any
      non-specific effects of current application. Laser Doppler flow (LDF, mean +/-
      SD; arbitrary units; AU) was recorded on the forearms of healthy volunteers
      during and 20 min following application of 0.10-mA current for 1, 3 and 5 min,
      using deionised water as a vehicle. Local heating to 44 degrees C was then
      applied for 24 min to assess maximal vasodilation. Cathodal current applications
      resulted in delayed and prolonged vasodilation (peak values: 78 +/- 29, 75 +/-
      19, 80 +/- 37 AU) whereas anodal peak LDF was 13 +/- 6, 27 +/- 34 and 72 +/- 40
      AU for 1-, 3- and 5-min periods of current applications, respectively. From
      current onset, inflexion points in the responses to 3- and 5-min anodal current
      applications occurred at 4.5 and 6.5 min, respectively, and at approximately 1.5
      min for all cathodal current applications. For 5-min current applications: a
      preliminary tourniquet ischaemia neither changed the time course nor the
      amplitude of the response to current application. In this situation, local
      anaesthesia abolished the current-induced vasodilation. Chronic capsaicin
      pretreatment decreased the amplitude of the vasodilation. Pretreatment with 500
      mg oral aspirin decreased the cathodal vasodilation and abolished the anodal
      vasodilation, even in the absence of preliminary ischaemia. We conclude that
      vasodilation to prolonged application of 0.10-mA continuous monopolar current
      after transient tourniquet ischaemia cannot be exclusively the result of an axon
      reflex initiated by current onset. This current-induced vasodilation is at least
      partly dependent on capsaicin-sensitive afferent fibres and relies on aspirin
      sensitive mechanisms at both polarities.

PMID- 11844939
TI  - Changes in the actin cytoskeleton of cardiac capillary endothelial cells during
      ischaemia and reperfusion: the effect of phalloidin on cell shape.
AB  - A reduction in capillary dimensions has been demonstrated in postischaemic
      reperfusion in the heart. The aim of this study was to demonstrate that in
      ischaemia and ischaemia followed by reperfusion, the change in shape of the
      constituent endothelial cells can be inhibited by phalloidin which stabilises the
      actin microfilament system. Isolated, perfused rat hearts were made globally
      ischaemic both with and without reperfusion and in the presence or absence of
      phalloidin. Changes in ischaemic endothelial cell dimensions were quantified by
      measuring whole capillary and luminal cross-sectional areas, abluminal and
      luminal membrane lengths. The distribution of beta-actin within the endothelial
      cells was determined by immunocytochemistry. In control hearts, beta-actin is
      distributed throughout the endothelium with a slight increase towards the luminal
      membrane. In ischaemia, this was more marked and other patterns of actin
      distribution were also observed. After reperfusion, a 'double ring' of actin
      could be distinguished. With phalloidin, the actin staining was more regular and
      the ring pattern was not observed. Morphometry showed that phalloidin was more
      effective in reducing endothelial cell shape change after reperfusion than after
      ischaemia alone. We conclude that endothelial cell shape change on reperfusion
      can be modified by agents which target the contractile proteins.

PMID- 11844940
TI  - Changes of sequestered leukocytes and platelets by inhalation prostaglandin E(1)
      in the pulmonary microvasculature of rats with monocrotaline-induced pulmonary
      hypertension.
AB  - The role of leukocytes (WBCs) and platelets (PLTs) in the pulmonary circulation
      may be important in the development of monocrotaline (MCT)-induced pulmonary
      hypertension in rats. We investigated the suppressive effects of long-term
      prostaglandin E(1) (PGE(1)) aerosol on the changes in WBCs and PLTs in the
      peripheral blood and the pulmonary microvasculature during the development of
      chronic pulmonary hypertension in MCT rats by real-time confocal scanning laser
      microscopy. The number of WBCs and PLTs in peripheral blood did not significantly
      change by inhalation of PGE(1). The number of WBCs and PLTs sequestered in the
      pulmonary microvasculature of rats subjected PGE(1) inhalation immediately after
      MCT injection rats with (MCT plus PGE(1) inhalation) significantly decreased from
      1 to 4 weeks compared to rats not subjected to PGE(1) inhalation (p < 0.01). The
      pulmonary systolic arterial pressure and the weight ratio of the right ventricle
      to the intraventricular septum plus the left ventricle (RV/IVS + LV weight ratio
      or RV weight ratio) in rats with MCT plus PGE(1) inhalation significantly
      decreased compared to rats not subjected to PGE(1) inhalation (p < 0.01). The
      levels of peripheral CD62L-positive WBCs in rats with MCT plus PGE(1) inhalation
      significantly decreased from 1 to 2 weeks compared to rats not subjected to
      PGE(1) inhalation, but the levels of peripheral CD18 and CD49d-positive WBCs did
      not significantly change. We conclude that long-term inhalation of PGE(1) is a
      very useful therapy in chronic pulmonary hypertension, and the mechanism of
      suppressing pulmonary hypertension is associated with suppressive effects on
      sequestered WBCs, especially CD62-positive WBCs and PLTs in the pulmonary
      microvasculature.

PMID- 11844942
TI  - A randomised controlled clinical trial on the additional effect of hypnosis in a
      comprehensive treatment programme for in-patients with conversion disorder of the
      motor type.
AB  - BACKGROUND: The primary aim of this study was threefold: (1) to examine the
      additional effects of hypnosis aimed at symptom reduction, using symptom-oriented
      and expression- and insight-oriented techniques in a comprehensive clinical
      treatment programme for in-patients with a persistent conversion disorder of the
      motor type; (2) to assess whether the level of hypnotisability was predictive of
      treatment outcome, and (3) to explore the efficacy of the total clinical
      treatment programme. METHODS: The study population consisted of 45 in-patients
      between 18 and 65 years of age meeting the DSM-III-R criteria for conversion
      disorder of the motor type or somatisation disorder with motor conversion
      symptoms. A randomised controlled clinical trial was undertaken. The primary
      outcome measures were the Video Rating Scale for Motor Conversion Symptoms, the
      D(isabilities) code items from the International Classification of Impairments,
      Disabilities and Handicaps and the Symptom Checklist-90. Measures of the
      credibility of treatment and patient expectations of treatment outcome were used
      as manipulation checks. Hypnotisability was measured using the Stanford Hypnotic
      Clinical Scale. RESULTS: Significant treatment results for all outcome measures
      were found for the total sample. These effects proved to be clinically
      significant. The use of hypnosis had no additional effect on treatment outcome.
      Hypnotisability was not predictive of treatment outcome. CONCLUSION: A
      comprehensive treatment programme, either with or without hypnosis, can be
      worthwhile for patients with long-standing conversion symptoms.

PMID- 11844943
TI  - Assessment of the efficacy of a cognitive-behavioural group psychotherapy
      programme for HIV-infected patients referred to a consultation-liaison psychiatry
      department.
AB  - BACKGROUND: Most HIV-infected patients attending a consultation-liaison
      psychiatry service show symptoms of anxiety and depression. The present study
      sought to evaluate the immediate and long-term efficacy of a structured cognitive
      behavioural group therapy reducing anxiety and depression in HIV-infected
      patients referred to a consultation-liaison psychiatry department, and to
      identify baseline variables predictive of greater improvement. METHODS: Repeated
      measures ANOVA was used to analyse changes in the Beck Depression Inventory (BDI)
      and the state subscale of the State/Trait Anxiety Inventory (STAI) administered
      to 39 participants at 4 time points: T1 (1 month before beginning the therapy),
      T2 (during the first session), T3 (during the last session) and T4 (3 months
      after the last session). The therapy consisted of 16 weekly 2-hour sessions
      following a structured time-limited cognitive-behavioural group psychotherapy
      programme. RESULTS: During the intervention time (between T2 and T3) an
      improvement was observed in depression and anxiety, which persisted after the 3
      month follow-up period (between T3 and T4). No changes were observed during
      baseline (between T1 and T2). Patients with higher levels of anxiety at baseline
      showed greater improvement in STAI state subscale scores. Transmission of HIV
      infection through intravenous drug use was associated with less improvement on
      the BDI. CONCLUSIONS: This is the first report of an ongoing study which suggests
      long-lasting efficacy of a structured cognitive-behavioural group psychotherapy
      programme in a heterogeneous sample of HIV-1-infected patients referred to a
      consultation-liaison psychiatry unit.

PMID- 11844944
TI  - Locus of control orientation in panic disorder and the differential effects of
      treatment.
AB  - BACKGROUND: In this study the effects of treatment with cognitive therapy,
      antidepressants or pill-placebo on the locus of control orientation in panic
      disorder patients were analysed, as well as the relation of this panic locus of
      control with panic frequency and cognitive measures of panic. METHODS: A
      Multidimensional Anxiety Locus of Control scale (MALC) was developed and
      completed with other measures (ACQ and BSQ) before and after treatment. Patients
      also kept a panic diary. RESULTS: Four subscales were derived from the MALC: one
      Internal, and three external (a Chance, a Medication, and a Therapist) locus of
      anxiety control orientation scales. Cognitive therapy was superior over pill
      placebo on most outcome measures whereas antidepressants were only superior in
      reducing the number of panic attacks. Treatment with cognitive therapy resulted
      in an increase of 'internal' anxiety control orientation and a decrease of
      'chance' and 'medication' orientation, in comparison with antidepressant therapy.
      The residualized gain scores on the MALC subscales correlated with clinical
      improvement in subjects treated with cognitive therapy only. CONCLUSIONS: Results
      suggest that the locus of control orientation is important in evaluating the
      differential effects of treatments in panic disorder. A differential effect on
      panic locus of control in favor of cognitive therapy in comparison to medication
      was found.

PMID- 11844945
TI  - Psychological mediation of a type of oxidative DNA damage, 8
      hydroxydeoxyguanosine, in peripheral blood leukocytes of non-smoking and non
      drinking workers.
AB  - BACKGROUND: The present study investigates whether the formation of 8
      hydroxydeoxyguanosine (8-OH-dG), a known oxidative DNA damage relevant to
      carcinogenicity, can be associated with psychological factors, in order to
      clarify the possible stress-cancer linkage from a genetic viewpoint. METHODS: We
      performed a cross-sectional study in which we examined the relationships of the
      levels of 8-OH-dG in peripheral blood leukocytes to various psychological
      factors, including the Profile of Mood States (POMS) and the Center for
      Epidemiologic Studies Depression Scale (CES-D) in 38 non-smoking and non-drinking
      workers (19 males and 19 females). RESULTS: The levels of 8-OH-dG in male
      subjects were negatively correlated with the Tension-Anxiety scores of the POMS.
      In contrast, the levels of 8-OH-dG in female subjects were positively correlated
      with the Depression-Rejection scores of the POMS and the CES-D scores, and
      negatively associated with the Vigor scores of the POMS, respectively. Male
      subjects who had self-blame coping strategy displayed significantly high levels
      of 8-OH-dG. Moreover, the worse the subjective closeness to parents in childhood,
      the higher the levels of 8-OH-dG became in male subjects. The levels of 8-OH-dG
      increased reliably in subjects who had experienced the loss of a close family
      member within 3 years, when compared with non-bereaved subjects. CONCLUSIONS:
      Psychological distress may be associated with cancer risk, although sex
      difference influences them. Inadequate coping styles, possibly resulting from a
      poor interpersonal relationship with parents since childhood, and experience of a
      relatively recent loss of a close family member also appear to influence the
      pathogenesis of cancer.

PMID- 11844946
TI  - Increased thymidylate synthase mRNA concentration in blood leukocytes following
      an experimental stressor.
AB  - BACKGROUND: While it is well documented that immune responses, e.g. proliferative
      responses, can be influenced by psychosocial factors, e.g. stress, less is known
      about the biological mechanisms mediating such influences. The aim of the present
      investigation was to study the effect of an experimental stressor on mRNA levels
      in peripheral blood leukocytes of thymidylate synthase (TS), a gene necessary for
      cell division, while investigating possible individual differences in stress
      reactivity. METHODS: Fifteen healthy subjects were investigated under three
      experimental conditions: (1) exposure to a computerized mental stressor; (2)
      relaxation, and (3) control. Measurements included TS mRNA levels, total
      leukocyte number, leukocyte subtypes, and serum cortisol before (baseline),
      immediately after, and 1 h after each experimental condition. RESULTS: While no
      significant differences were found between experimental conditions at baseline in
      cortisol (p = 0.9) or TS mRNA levels (p = 0.1), significantly higher TS mRNA
      expression was found immediately after stress compared to pretreatment levels (p
      < 0.02). Changes in cortisol levels indicated an effect of the experimental
      stressor, with higher cortisol levels seen immediately after stress as compared
      to both relaxation (p < 0.01) and control (p < 0.01). Subjects who scored above
      the median on the Tellegen Absorption Scale showed significantly (p < 0.05)
      greater increases in cortisol and percentage of lymphocytes and significantly
      greater decreases in percentage of neutrophil cells after stress. CONCLUSION: The
      results suggest that TS mRNA levels in peripheral leukocytes may be sensitive to
      mental stress and confirm previous findings indicating that subjects scoring high
      on the personality trait of absorption exhibit greater physiological stress
      reactivity.

PMID- 11844947
TI  - The relationship between dissociative proneness and alexithymia.
AB  - BACKGROUND: Dissociative reactions and alexithymia are two strategies that have
      been put forward as coping mechanisms to alleviate painful emotions. It is the
      clinical impression that dissociation is related to certain alexithymia features.
      In line with the coping hypothesis, it was predicted that the relationship
      between dissociative tendencies and alexithymia would be partly mediated by
      current levels of stress and/or by past traumatic experiences. Furthermore,
      dissociation may also be related to enhanced fantasizing, although alexithymia
      has traditionally been associated with an incapacity to fantasize. METHODS: Data
      were obtained from 833 nonclinical participants on dissociative tendencies,
      alexithymia, childhood abuse, current stress and socially desirable behavior.
      Correlation analyses followed by multiple regression were performed. RESULTS:
      Dissociative tendencies appeared to be especially related to one alexithymic
      feature: a difficulty in identifying feelings. This relationship was partially
      mediated by levels of current stress. A history of trauma did not predict
      dissociation measures. Furthermore, highly dissociative participants were more
      fantasy prone than low-dissociative participants. CONCLUSIONS: The results of
      this study support the idea that in a nonclinical group dissociation may provide
      a way to cope with current stressful events, and that this is associated with a
      difficulty in identifying feelings. It is argued that two types of dissociation
      may exist, one trait-like type of dissociation that is associated with fantasy
      proneness and other related factors, and a trauma-related type of dissociation
      that is more apparent within the clinical range.

PMID- 11844948
TI  - Psychological well-being in rheumatoid arthritis: relationship to 'disease'
      variables and affective disturbance.
AB  - BACKGROUND: Resilience is likely to be important in understanding psychological
      responses to chronic physical illnesses. This study aimed to examine one measure
      of resilience--Ryff's operationalized measure of psychological well-being (PWB)-
      in rheumatoid arthritis. It was hypothesized that PWB would be influenced by age
      and gender in the same way as in community samples, and that the absence of
      current mood disorder would be associated with high PWB. METHODS: Rheumatology
      clinic outpatients (n = 104) were assessed for pain, disease activity,
      disability, depression and anxiety. PWB was assessed using Ryff's six-subscale
      model. The measured variables were used in a logistic regression analysis to
      model the absence of clinically important mood disorder. RESULTS: The expected
      variations in PWB according to age and gender were largely absent, with the
      overall findings suggesting that chronic illness in general, rather than
      arthritis in particular, affects PWB. Significant bivariate correlations were
      found between depression and pain, disease activity, disability and all six PWB
      subscales. However, in the regression analysis, only the PWB environmental
      mastery subscale and self-rated disability made significant contributions to the
      absence of mood disturbance, and their inclusion in the regression model
      correctly classified 81% of the total sample. CONCLUSIONS: These results require
      replication in a longitudinal study, but indicate the potential value of using
      PWB among people with rheumatoid arthritis to screen for individuals who may be
      particularly vulnerable to developing depression. It might be appropriate to
      target such people with focused psychological interventions.

PMID- 11844949
TI  - Physiological changes associated with downsizing of personnel and reorganisation
      in the health care sector.
AB  - BACKGROUND: The objective of this study was to assess potential physiological
      changes associated with downsizing/reorganisation in the health care sector. The
      personnel reductions (1995-1997) in the studied regional hospital corresponded to
      one fifth of the personnel. METHODS: In a longitudinal study, female personnel
      had blood sampled twice (8 a.m. and 4 p.m.) during a working day in 1997 (in
      connection with the last completed round of personnel redundancies) and 1 year
      later in 1998. The participants were 31 women (82% of those initially sampled );
      there were 14 registered nurses, 11 assistant nurses and 6 medical secretaries.
      No additional drop outs took place during follow-up. Outcome variables were
      changes in the difference in serum cortisol levels between the morning and
      afternoon and in serum/plasma concentrations of immunoglobulin G (IgG),
      oestradiol, dehydroepiandrosterone sulphate (DHEAS), prolactin and
      apolipoproteins AI and B. RESULTS: Significantly decreased serum/plasma
      concentrations of IgG (p < 0.001), apolipoprotein AI (p < 0.001) and oestradiol
      (p < 0.001) were found. The difference between morning and afternoon serum
      cortisol decreased, with a change at the significance level of p = 0.05. No
      significant changes were observed regarding prolactin, DHEAS and apolipoprotein
      B. CONCLUSIONS: These results could be an indication that protective and anabolic
      functions had suffered in these remaining 'ageing' female work groups. The
      circadian cortisol rhythm was possibly flattened, which could be a sign of
      physiological dysfunction associated with the long-lasting adaptation process.
      These conclusions are tentative, given the small size of the sample and the lack
      of a control group. However, the findings point to the significance of studies of
      physiological changes possibly associated with restructuring of the health care
      sector.

PMID- 11844950
TI  - Stressful life events and skin diseases: an additional perspective from research
      on psychosomatic dynamics in systemic lupus erythematosus.

PMID- 11844954
TI  - What is new with tobacco dependence.

PMID- 11844955
TI  - The neurobiology of tobacco dependence: a commentary.
AB  - This commentary summarises the evidence that nicotine has the pharmacological
      properties of a psychostimulant drug of dependence. Behaviourally it serves as a
      reinforcer in self-administration experiments. Within the brain, acute nicotine
      stimulates the release of dopamine (DA) in the shell of the nucleus accumbens
      whereas repeated nicotine results in selective sensitization of its effects on DA
      overflow in the accumbal core. These effects are thought to play a central role
      in the acquisition of responding for nicotine and the development of associations
      between delivery of the drug and cues that predict its delivery. These responses,
      therefore, are thought to be pivotal to its ability to cause dependence. The
      commentary also emphasises the evidence that cigarette smoke provides a vehicle
      for nicotine that maximises its addictive potential since it delivers nicotine
      directly into the lungs and, within 10-15 s, to the brain. For habitual cigarette
      smokers, this process is repeated frequently and regularly and in the context of
      many other sensory cues within the smoke that potentially provide additional
      conditioned reinforcers. This, it is argued, explains the strong addiction that
      many smokers develop to tobacco smoke. Smoking cessation is also associated with
      the expression of an abstinence syndrome that can, largely, be attributed to
      nicotine withdrawal and is also likely to contribute to the maintenance of the
      habit. The commentary closes with a brief review of the pharmacological
      mechanisms that may contribute to the efficacy of nicotine replacement therapy
      and Zyban (bupropion) as aids to smoking cessation.

PMID- 11844956
TI  - Problems associated with diaphragm pacing.

PMID- 11844957
TI  - A potentially fatal complication of Mycoplasma pneumoniae infection--the
      hemophagocytic syndrome.

PMID- 11844958
TI  - Validation of a central review board of staging prior to surgery for non-small
      cell lung cancer--impact on prognosis: a multicenter study.
AB  - BACKGROUND: In non-small-cell lung cancer (NSCLC), the evaluation of anatomic
      tumor extension [tumor, node, metastasis (TNM) stage] is indispensable for the
      exchange of scientific information or determining prognosis. OBJECTIVE: To
      quantify changes in TNM stages (numerical migration) and survival (prognostic
      migration) resulting from the application of classificatory certainty criteria to
      patients with NSCLC who had undergone surgical treatment. METHODS: The study
      population included 1,844 patients registered by the Bronchogenic Carcinoma
      Cooperative Group of the Spanish Society of Pneumology and Thoracic Surgery (GCCB
      S). For every patient, two evaluations were made of each component of the TNM
      classification: an initial classification, defined by a local representative, and
      a confirmed classification resulting from the application of stricter
      classificatory criteria by the GCCB-S Central Review Board. RESULTS: The results
      revealed scant numerical migration in the cT category (11.5% of the study
      population) and a general tendency toward a downstaging. In contrast, the initial
      cN1 category experienced a complete numerical migration and the initial cN2
      category a very large numerical migration (from 200 to 22 cases). In the small
      group of patients for whom there was a classificatory change in cT (n = 212), the
      migration for the cT2 category was accompanied by a less favorable prognosis (p =
      0.039, log-rank test). However, the migration of this small subset of patients
      did not affect the general prognosis of the study population for cT2. In cN2, the
      3-year survival rate migrated from 0.42 to 0.29. CONCLUSIONS: Numerical migration
      resulting from the application of stricter classificatory criteria was relevant,
      but had little, although unfavorable, global prognostic impact.

PMID- 11844959
TI  - Prognostic value of serum tumor markers in patients with lung cancer.
AB  - BACKGROUND: The role of tumor markers in the diagnosis and prognosis of lung
      cancer is under investigation. OBJECTIVES: The aim of this study was to
      investigate the diagnostic and prognostic significance of pre-therapeutic levels
      of various serum tumor markers, CYFRA 21-1, neuron-specific enolase (NSE), tissue
      polypeptide antigen (TPA), carcinoembryonic antigen (CEA), CA 125 and squamous
      cell carcinoma antigen (SCCAg), in patients with lung cancer. METHODS: We studied
      102 consecutive patients (mean age 65.2 +/- 11 years) with newly diagnosed lung
      cancer (96 males, 94%, with a mean age of 66.3 +/-10.5 years). All patients had a
      5-year follow-up. Measurements of the serum tumor markers were performed on
      initial diagnosis. RESULTS: Eighty-four patients (82%) had non-small-cell lung
      cancer (NSCLC) and 18 (18%) small-cell lung cancer (SCLC). From the 84 patients
      with NSCLC, 34 patients (33%) had squamous-cell lung cancer, 23 (22%)
      adenocarcinoma and 23 (22%) large-cell carcinomas. The overall median survival
      was 8.5 months. All SCLC patients had extensive disease with a median survival of
      10.1 months and NSCLC patients of 8.4 months. Significant differences in the mean
      values of NSE and CYFRA 21-1 were observed between SCLC and NSCLC. In NSCLC,
      CYFRA 21-1, TPA, CA 125 and SCCAg serum levels were related to the stage of the
      disease at diagnosis, and CYFRA 21-1, NSE, TPA and CA-125 were related to a poor
      outcome. None of the above tumor markers was related to survival in the SCLC
      group. CONCLUSION: CYFRA 21-1 and NSE may help to differentiate cell types in
      lung cancer patients. Also, CYFRA 21-1 with TPA and CA 125 may provide useful
      information regarding the staging of the disease at diagnosis and the prognosis
      of patients with NSCLC.

PMID- 11844961
TI  - Seasonal difference in the occurrence of exercise-induced bronchospasm in
      asthmatics: dependence on humidity.
AB  - BACKGROUND: Most studies on the effects of temperature and humidity on exercise
      induced bronchospasm (EIB) in asthmatics have been carried out under indoor
      conditions. However, any asthmatic patient is exposed to varying climatic
      conditions. OBJECTIVE: To investigate whether temperature or relative humidity
      plays a more important role in determining the degree of EIB in asthmatics under
      naturally exposed climate conditions. METHODS: To exclude the effects of pollen
      on EIB, we enrolled 69 subjects with perennial asthma (mean +/- SD: 20.1 +/- 1.5
      years). The subjects performed outdoor free running tests. They were divided into
      winter (n = 25), spring/autumn (n = 22), and summer (n = 22) groups according to
      the season when they performed the tests. Initial spirometry and skin prick tests
      were performed. Methacholine bronchial challenge testing and, one day later, the
      free running tests were done. RESULTS: There were significant differences in
      temperature and relative humidity among the three groups: However, the relative
      humidity in winter did not differ from that in spring/autumn. There were no
      differences in pulmonary functions, airway responsiveness, and atopy score among
      the three groups. The percentage of cases of positive EIB --fall in forced
      expiratory volume in 1s FEV(1) of >15% from baseline --in winter (84%, p < 0.05)
      or spring/autumn (86.4%, p < 0.05) was higher than that in summer (50%). However,
      the percentage of subjects with a positive EIB in winter did not differ from that
      in spring/autumn. The maximal percent fall in FEV(1) after exercise in winter did
      not differ from that in spring/autumn. CONCLUSIONS: The occurrence of EIB is
      associated with environmental temperature and humidity. Under such climatic
      conditions as in Korea, relative humidity may be a more important factor than
      temperature in contributing to EIB in patients with perennial asthma.

PMID- 11844960
TI  - Correlation among the indices of high-resolution computed tomography, pulmonary
      function tests, pulmonary perfusion scans and exercise tolerance in cases of
      chronic pulmonary emphysema.
AB  - BACKGROUND: Mismatched distribution of pulmonary blood flow is a common
      characteristic in emphysematous patients. But few reports have mentioned the
      relationships between the morphological changes in the lungs as assessed by high
      resolution computed tomography (HRCT), pulmonary blood flow (PBF) scan and the
      indices of exercise tolerance. We investigated these relationships. OBJECTIVE:
      Pulmonary function tests (PFT), HRCT, single photon emission computed tomography
      ((99m)SPECT) and treadmill exercise tests were performed on emphysematous
      patients, and the correlations between these examinations were studied. METHODS:
      We evaluated 20 patients (M 18, F 2, age 66 +/- 8.0 years). CT evaluation was
      performed according to the grade of emphysematous change. (99m)SPECT was
      performed to evaluate mismatched PBF by the score method. The better flow of the
      middle lobe was selected to be the standard lobe for the basic PBF. That score
      was set to 1 when the blood flow was below 60 or above 140%. PBF between 60 and
      140% was scored as 0. RESULTS: FEV(1 )(r = 0.648, p = 0.002) and VC (r = 0.767, p
      = 0.001) correlated significantly with Vdot;O(2) peak. FEV(1) (r = 0.667, p =
      0.0018) correlated significantly with anaerobic threshold (AT). CT grade did not
      correlate with PBF mismatch score (r = 0.266, p = 0.3376). %Vdot;O(2 )peak did
      not correlate with CT grade (r = -0.467, p = 0.0689) or with mismatch PBF score
      (r = -0.327, p = 0.2377). CONCLUSIONS: HRCT and (99m)SPECT were advantageous for
      detecting the progression of disease and emphysematous changes. However, the
      severity of anatomical emphysematous changes did not necessarily correlate with
      the indices of exercise tolerance and pulmonary function tests.

PMID- 11844962
TI  - Expression of human beta defensin (HBD-1 and HBD-2) mRNA in nasal epithelia of
      adult cystic fibrosis patients, healthy individuals, and individuals with acute
      cold.
AB  - BACKGROUND: Lack or inactivation of defensins may facilitate chronic bacterial
      colonization in the cystic fibrosis (CF) lung. CF nasal epithelium exhibits
      typical biochemical abnormalities and can be used to study defensin expression in
      CF. OBJECTIVES: To evaluate the expression of beta defensin (HBD-1 and HBD-2)
      mRNA and the presence of inflammatory markers (percentage of neutrophils and IL-8
      mRNA expression) in CF and non-CF nasal mucosa. METHODS: Case-control study.
      Nasal brushing samples were obtained from 22 stable adult CF patients and 32 non
      CF controls (25 healthy individuals and 7 individuals with acute cold). Samples
      were subjected to analysis involving mRNA expression (semiquantitative RT-PCR)
      and differential cell counting. RESULTS: Defensins and inflammatory markers were
      expressed at low levels in healthy individuals and at high levels in subjects
      with acute cold. In non-CF controls, defensin expression correlated significantly
      with inflammatory parameters (p < 0.001). In CF, defensin mRNA expression was
      comparable to healthy individuals (p = 0.2). In contrast to non-CF controls, in
      CF patients high levels of inflammatory markers did not correlate with defensin
      mRNA levels. CONCLUSIONS: Defensin expression is not upregulated in CF epithelium
      in response to inflammatory stimuli. Further studies are necessary to elucidate
      whether this is a consequence of the CF gene mutation.

PMID- 11844963
TI  - Prevalence of byssinosis and respiratory symptoms among cotton mill workers.
AB  - BACKGROUND: While the prevalence of byssinosis is decreasing in industrialized
      countries and persists at high levels in developing countries, this prevalence is
      remaining constant in Turkey. OBJECTIVE: In order to determine the effects of
      past cotton dust exposure on the respiratory tract, a total of 223 persons
      working in a cotton mill were included in this study. METHODS: A questionnaire
      was used to inquire about respiratory symptoms. Participants underwent several
      spirometric measurements, which were performed on the 1st, 3rd and 5th day of the
      working week. Cotton dust measurements were performed in different divisions of
      the factory. RESULTS: The most common respiratory symptom was chest tightness
      (20.3%). The prevalence of byssinosis was 14.2% in cotton-processing workers.
      Among these cases, 28.6% had symptoms on the 1st day of the week, and 71.4% had
      symptoms on all days of the week. An acute effect was seen in 53.6% of the
      workers with byssinosis. Mean respirable dust levels were between 0.095 and 0.413
      mg/m(3). CONCLUSIONS: In spite of technological improvements, respirable dust
      concentrations are still above the permissible limits, and thus the risk of
      byssinosis remains. Workers in the cotton industry where obsolete technology is
      used and standardized protection measures are not applied should be followed for
      byssinosis.

PMID- 11844964
TI  - Surfactant replacement for ventilator-associated pneumonia: a preliminary report.
AB  - BACKGROUND: Surfactant abnormalities have been described in bacterial pneumonia.
      OBJECTIVE: To determine the safety and effect of exogenous surfactant replacement
      in patients with ventilator-associated pneumonia (VAP). METHODS: Patients with
      VAP were randomized in a double-blind study to receive either an artificial
      surfactant (Exosurf) consisting mostly of disaturated phospholipids (DSPL) or
      saline via a continuous nebulizer system for 5 days. Patients underwent
      bronchoscopy and bronchoalveolar lavage (BAL) prior to and after 4 days of
      therapy. RESULTS: Twenty-two patients were randomized, with 8 receiving Exosurf.
      There was no detected difference in outcome between the saline- and Exosurf
      treated patients in terms of days on ventilator, 30-day or hospital mortality. At
      the follow-up lavage, the patients treated with Exosurf had a significant rise in
      the level of DSPL (p < 0.05), while the saline group did not, suggesting delivery
      of drug. Also at the follow-up lavage, the percentage of neutrophils in the BAL
      fell in the Exosurf patients (p < 0.01), but not in the saline group. CONCLUSION:
      Exogenous surfactant replacement given to patients with VAP increased the amount
      of DSPL retrieved by BAL. This treatment was associated with a fall in the
      neutrophil response to pneumonia.

PMID- 11844965
TI  - Ultrathin bronchoscopy as an adjunct to standard bronchoscopy in the diagnosis of
      peripheral lung lesions. A preliminary report.
AB  - BACKGROUND: The role of the standard bronchoscope as a method of diagnosis of
      peripheral lung lesions is limited. OBJECTIVES: To evaluate the role of the
      ultrathin bronchoscope as an adjunct to standard bronchoscopy in the diagnosis of
      peripheral lung lesions. METHODS: Seventeen consecutive patients with a
      peripheral lung lesion on chest radiography or chest CT. All patients underwent a
      bronchoscopic examination with a standard size bronchoscope, and if there was no
      evidence of endobronchial lesion, these patients were subsequently examined with
      an Olympus 3C40 ultrathin bronchoscope (external diameter of 3.6 mm). Under
      fluoroscopic guidance, cytological brushing samples were taken with the ultrathin
      bronchoscope followed by a reexamination with the standard bronchoscope which
      followed the same 'pathway' to the lesion established by the 3C40 ultrathin
      bronchoscope. Transbronchial biopsies (TBB) and cytological samples were taken
      with the standard bronchoscope. RESULTS: The size of the lesions ranged from 1.5
      to 7.0 cm. A positive bronchoscopic diagnosis by TBB was obtained in 11 out of 17
      patients (64.7%) and a diagnosis of atypical cells suspicious for malignancy
      noted in a further 3 patients. For lesions less than 3 cm in size, a positive
      diagnosis by TBB was achieved in 7 out of 10 of these cases. The lesion was
      directly visualized with the ultrathin bronchoscope in 4 cases. CONCLUSIONS:
      Ultrathin bronchoscopy appears to be a useful adjunct to standard bronchoscopy by
      providing an accurate pathway to the lesion in question. However, further studies
      with larger patient groups are warranted.

PMID- 11844966
TI  - Thoracoscopic electrode implantation for diaphragm pacing in dogs.
AB  - BACKGROUND: Diaphragm pacing is an attractive method of ventilatory support;
      however, it requires electrode implantation to the phrenic nerve or diaphragm.
      The thoracic approach is favored for several reasons, and it usually accompanies
      invasive bilateral thoracotomy. OBJECTIVES: This study was conducted to develop a
      new electrode suitable for video-assisted thoracoscopic implantation, which is
      less invasive than the conventional thoracic approach. METHODS: The feasibility
      of video-assisted thoracoscopic implantation was tested with newly designed
      electrodes using 5 mongrel dogs. Furthermore, diaphragm pacing was performed for
      60 min to test whether or not the implanted electrodes were functional. RESULTS:
      Video-assisted electrode implantation was successful in all 5 cases. No
      complications occurred during the implantation procedure. In acute-phase pacing
      trials, the electrodes stimulated the phrenic nerves for 60 min without any
      pacing failures. The mean value of PaCO(2) increased gradually from 32.2 +/-
      (SEM) 1.52 to 54.6 +/- 4.58 mm Hg, and the value of tidal volume decreased
      gradually from 242.9 +/- 31.3 to 147.5 +/- 24.5 ml in 60 min pacing. CONCLUSIONS:
      The thoracoscopic implantation of new electrodes was less invasive, and was a
      safe procedure for diaphragm pacing. Meticulous care should be taken to avoid
      muscle fatigue.

PMID- 11844967
TI  - Effects of almitrine on diaphragm contractile properties in young and old rats.
AB  - BACKGROUND: Diaphragm muscle force and fatigue are key factors in the development
      of respiratory failure. Almitrine is used to improve ventilatory drive and
      ventilation-perfusion matching in respiratory failure. Recently, it has also been
      shown to improve diaphragm muscle force and endurance in young rats, but it is
      not known if this effect persists with ageing. OBJECTIVES: To determine the
      effects of almitrine on diaphragm contractile properties in young and old rats.
      METHODS: In young and old rats, isometric contractile properties were measured in
      strips of isolated diaphragm muscle in physiological saline solution at 30
      degrees C with or without almitrine. RESULTS: In young animals, almitrine
      increased twitch tension, reduced half-relaxation time and increased endurance,
      but had no effect on tetanic tension, contraction time or tension-frequency
      relationship. Ageing had no effect on endurance, but did reduce twitch and
      tetanic tension and contraction and half-relaxation time. Almitrine had no effect
      on contractile tension and kinetics, tension-frequency relationship or on
      endurance in the old animals. CONCLUSIONS: Ageing negates the beneficial effects
      of almitrine on diaphragm muscle force and endurance.

PMID- 11844968
TI  - A fast amplification-reverse hybridization assay kit to detect the most frequent
      deficient variants in the alpha-1-antitrypsin gene.
AB  - BACKGROUND: There is worldwide growing awareness of alpha-1-antitrypsin
      deficiency (AATD), a major hereditary disorder in Caucasians. The gold standard
      for its laboratory diagnosis is thin-layer isoelectric focusing, which should be
      performed in reference laboratories. OBJECTIVES: The aim of this study was to
      check the characteristics of a commercially available amplification-reverse
      hybridization assay kit in detecting at a molecular level the alpha-1-antitrypsin
      (AAT) Z and S variants, i.e. the most frequent variants associated with AATD, by
      comparing its performance with DNA restriction fragment length polymorphism.
      METHODS: We studied samples from 36 subjects enrolled in the Italian National
      Registry for Severe Alpha-1-antitrypsin Deficiency. Based on previous plasma
      isoelectric focusing typing, we selected samples with the following phenotypes:
      MM (9 samples), MS (9 samples), SZ (3 samples), MZ (11 samples), ZZ (3 samples),
      and a rare variant (1 sample). DNA was extracted by the standard method. The
      presence of the AAT Z and S gene variants was determined by the amplification
      reverse hybridization test kit, following the manufacturer's instructions, and by
      the restriction fragment length polymorphism technique, according to established
      procedures. RESULTS: We found that the identification of the AAT Z and S gene
      variants obtained by the amplification-reverse hybridization test kit was
      completely in agreement with that obtained by the restriction fragment length
      polymorphism technique. CONCLUSIONS: We conclude that the test kit provides a
      fast, easy and unambiguous identification of Z and S alleles. Because of its
      transferability to routine laboratories, the test kit may be useful in
      identifying cases of severe AATD, thus resulting in increasing awareness of this
      rare disorder.

PMID- 11844969
TI  - Respiratory failure in Arnold-Chiari malformation.

PMID- 11844970
TI  - An elderly patient with hemophagocytic syndrome due to severe mycoplasma
      pneumonia with marked hypercytokinemia.
AB  - We present an extremely rare case of hemophagocytic syndrome (HPS) induced by
      fulminant Mycoplasma pneumoniae (Mp) pneumonia in an elderly adult.
      Erythrocytopenia and thrombocytopenia were observed in a patient with acute
      respiratory failure, liver dysfunction and renal failure. Mp-associated HPS was
      diagnosed in this case by clinical and laboratory findings, including a bone
      marrow aspiration specimen and serum Mp antibody titer. High serum levels of
      soluble interleukin-2 receptor, interleukin-6, human interleukin-10 and
      macrophage-colony stimulating factor were observed. Hypercytokinemia is a useful
      marker of disease activity and prognosis. Combined treatment with
      methylprednisolone and erythromycin was successful and led to a favorable
      outcome. Physicians should be aware of HPS as a complication in Mp infection.

PMID- 11844971
TI  - Double aortic arch masquerading as asthma for thirty years.
AB  - A case of a 30-year-old woman with a double-barrelled aorta misdiagnosed as
      asthma is presented. The patient was significantly improved after surgical
      treatment but a degree of airway symptoms persisted. She was further investigated
      and diagnosed with tracheomalacia. The paediatric experience with managing
      tracheomalacia is briefly reviewed and recommendations for the treatment of the
      rare adult cases are made. Our report emphasises the importance of early
      diagnosis and treatment of aortic arch abnormalities.

PMID- 11844973
TI  - Bronchiolitis obliterans in a case of juvenile rheumatoid arthritis presented
      with pneumomediastinum.
AB  - We present a case of bronchiolitis obliterans associated with juvenile rheumatoid
      arthritis in whom pneumomediastinum was the presenting manifestation. Diagnosis
      of bronchiolitis obliterans was made on the basis of the clinical history,
      pulmonary function tests and high-resolution computerized tomography scan
      findings. Pneumomediastinum resolved in a few days following high-dose nasal
      oxygen. This case shows that bronchiolitis obliterans can occur in patients with
      juvenile rheumatoid arthritis. Complicating pneumomediastinum in such cases
      should be considered as an indication of underlying bronchiolitis obliterans.

PMID- 11844972
TI  - Massive pleural effusion as the presenting feature of a subarachnoid-pleural
      fistula.
AB  - A 14-year-old boy presented with a large symptomatic transudative pleural
      effusion 4 months after spinal surgery for kyphoscoliosis. Computed tomography
      myelography confirmed a subarachnoid-pleural fistula (SPF) with a pseudo
      meningocele communicating with the left pleural space. A review of the literature
      indicates this to be a rare finding. The possibility of SPF should be entertained
      in patients who present with a pleural effusion following transthoracic spinal
      surgeries.

PMID- 11844974
TI  - Pulmonary nodules with the CT halo sign.

PMID- 11844975
TI  - Failure of inhaled corticosteroids to improve small airway obstruction in two
      patients with sarcoidosis.

PMID- 11844976
TI  - Conjugated linoleic acid in humans--reasons to be cheerful?

PMID- 11844977
TI  - Efficiency of conversion of alpha-linolenic acid to long chain n-3 fatty acids in
      man.
AB  - Alpha-linolenic acid (18:3n-3) is the major n-3 (omega 3) fatty acid in the human
      diet. It is derived mainly from terrestrial plant consumption and it has long
      been thought that its major biochemical role is as the principal precursor for
      long chain polyunsaturated fatty acids, of which eicosapentaenoic (20:5n-3) and
      docosahexaenoic acid (22:6n-3) are the most prevalent. For infants, n-3 long
      chain polyunsaturated fatty acids are required for rapid growth of neural tissue
      in the perinatal period and a nutritional supply is particularly important for
      development of premature infants. For adults, n-3 long chain polyunsaturated
      fatty acid supplementation is implicated in improving a wide range of clinical
      pathologies involving cardiac, kidney, and neural tissues. Studies generally
      agree that whole body conversion of 18:3n-3 to 22:6n-3 is below 5% in humans, and
      depends on the concentration of n-6 fatty acids and long chain polyunsaturated
      fatty acids in the diet. Complete oxidation of dietary 18:3n-3 to CO2 accounts
      for about 25% of 18:3n-3 in the first 24 h, reaching 60% by 7 days. Much of the
      remaining 18:3n-3 serves as a source of acetate for synthesis of saturates and
      monounsaturates, with very little stored as 18:3n-3. In term and preterm infants,
      studies show wide variability in the plasma kinetics of 13C n-3 long chain
      polyunsaturated fatty acids after 13C-18:3n-3 dosing, suggesting wide variability
      among human infants in the development of biosynthetic capability to convert
      18:3n-3 to 22:6n3. Tracer studies show that humans of all ages can perform the
      conversion of 18:3n-3 to 22:6n3. Further studies are required to establish
      quantitatively the partitioning of dietary 18:3n-3 among metabolic pathways and
      the influence of other dietary components and of physiological states on these
      processes.

PMID- 11844978
TI  - Long-chain polyunsaturated fatty acid accretion in brain.
AB  - Brain is highly enriched in long-chain polyunsaturated fatty acids (PUFAs),
      particularly arachidonic acid and docosahexaenoic acid, which play important
      roles in brain structural and biologic functions. Plasma transport, in the form
      of free fatty acids or esterified FAs in lysophosphatidylcholine and
      lipoproteins, and de-novo synthesis contribute to brain accretion of long-chain
      PUFAs. Transport of long-chain PUFAs from plasma may play important roles because
      of the limited ability of brain to synthesize long-chain PUFAs, in the face of
      high demand for them. Although several proteins involved in facilitated fatty
      acid transport (e.g. fatty acid transport protein, fatty acid binding protein and
      very-long-chain acyl-coenzyme A synthetase) have been found in brain, their roles
      in fatty acid accumulation in brain are poorly defined. The primary pathways that
      are involved in long-chain PUFA accumulation in brain may vary according to brain
      region and developmental stage.

PMID- 11844979
TI  - Role of CD36 in membrane transport of long-chain fatty acids.
AB  - CD36 is a multispecific membrane glycoprotein that has been postulated to have a
      variety of functions. Evidence generated in isolated cells and in mice and rat
      models of altered CD36 expression has indicated an important role for CD36 in
      membrane transport of long-chain fatty acids. The cumulative data indicate that
      CD36 facilitates a major fraction of fatty acid uptake by muscle and fat, and
      that CD36 deficiency is associated with a large (60-80%) defect in fatty acid
      uptake by those tissues. In humans, polymorphisms in the CD36 gene may underlie
      defective fatty acid metabolism and some forms of heart disease. Herein we review
      our current understanding of the transport function and regulation of CD36. The
      realization that the transport step rate limits cellular fatty acid utilization
      suggests that abnormalities in CD36 expression or function may impact on
      susceptibility to certain metabolic diseases such as obesity and insulin
      resistance.

PMID- 11844980
TI  - Plant sterols and blood lipid levels.
AB  - Plant sterols have recently been recommended by the National Cholesterol
      Education Panel for use with the more traditional approaches of limiting
      saturated fat and cholesterol intakes, maintaining a healthy body weight and
      engaging in regular exercise, as a non-pharmacological approach to reduce low
      density lipoprotein cholesterol levels. Recent data confirm the original
      observation that approximately 1.6 g of plant sterol esters per day results in a
      maximal low-density lipoprotein cholesterol lowering of approximately 10%. Few
      side-effects of plant sterols have been reported, with the exception of decreased
      levels of circulating carotenoids.

PMID- 11844981
TI  - Changes in the concentration and composition of plasma lipoproteins during the
      acute phase response.
AB  - The acute phase reactions, associated with injury, inflammation, or sepsis,
      markedly affect the concentration and composition of plasma lipids and
      lipoproteins. Hepatic production of triglycerides and very low density
      lipoprotein formation are increased, but do not necessarily result in high plasma
      triglyceride levels. In contrast, all conditions lower plasma cholesterol by
      decreasing its content in both low-density and high-density lipoproteins. In
      addition, substantial changes in protein and lipid composition of lipoproteins
      are observed that may redefine the function of these particles, but also increase
      their atherogenic and inflammatory properties.

PMID- 11844983
TI  - Bacterial translocation: effects of artificial feeding.
AB  - The most striking observation when reviewing recent literature in the field of
      bacterial translocation in the intestine is the small number of publications
      involving human subjects. Although there are some excellent reviews in this field
      published during the last 2 years, all experimental contributions come from
      animal experiments. It is therefore crucial to evaluate how valid the animal
      models are for human pathophysiology. Studies focusing on translocation as a
      major pathogenic mechanism are urgently needed to help clinicians to make correct
      decisions concerning protection of the gut and decide upon nutrition in the
      intensive care unit.

PMID- 11844984
TI  - Reactive oxygen species as mediators of organ dysfunction caused by sepsis, acute
      respiratory distress syndrome, or hemorrhagic shock: potential benefits of
      resuscitation with Ringer's ethyl pyruvate solution.
AB  - Reactive oxygen species are reactive, partly reduced derivatives of molecular
      oxygen. Important reactive oxygen species in biological systems include
      superoxide radical anion, hydrogen peroxide, and hydroxyl radical. Peroxynitrite,
      is another important species in biological systems. A variety of enzymatic and
      non-enzymatic processes can generate reactive oxygen species in mammalian cells.
      An extensive body of experimental evidence from studies using animal models
      supports the view that reactive oxygen species are important in the pathogenesis
      of ischemia-reperfusion syndromes, sepsis, acute respiratory distress syndrome,
      and multiple organ dysfunction syndrome. This view is further supported by data
      from clinical studies that correlate biochemical evidence of reactive oxygen
      species-mediated stress with the development of acute respiratory distress
      syndrome or sepsis in patients. Ethyl pyruvate, a simple derivative of pyruvic
      acid, has been shown to be efficacious in several animal models of critical
      illness, and warrants further evaluation in this regard.

PMID- 11844985
TI  - Poly(adenosine 5'-diphosphate) ribose polymerase activation as a cause of
      metabolic dysfunction in critical illness.
AB  - Poly(adenosine 5'-diphosphate) ribose polymerase is a nuclear enzyme activated in
      response to genotoxic stress induced by a variety of DNA damaging agents. Several
      oxygen and nitrogen-centered free radicals, notably peroxynitrite, are strong
      inducers of DNA damage and poly(adenosine 5'-diphosphate) ribose polymerase
      activation in vitro and in vivo. Activation of this nuclear enzyme depletes the
      intracellular stores of its substrate nicotinamide adenine dinucleotide, slowing
      the rate of glycolysis, mitochondrial electron transport and adenosine
      triphosphate formation. This process triggers a severe energetic crisis within
      the cell, leading to acute cell dysfunction and cell necrosis. Poly(adenosine 5'
      diphosphate) ribose polymerase also plays an important role in the regulation of
      inflammatory cascades, through a functional association with various
      transcription factors and transcription co-activators. Recent works identified
      this enzyme as a critical mediator of cellular metabolic dysfunction,
      inflammatory injury, and organ damage in conditions associated with overwhelming
      oxidative stress, including systemic inflammation, circulatory shock, and
      ischemia-reperfusion. Accordingly, pharmacological inhibitors of poly(adenosine
      5'-diphosphate) ribose polymerase protect against cell death and tissue injury in
      such conditions, and may therefore represent novel therapeutic tools to limit
      multiple organ damage and dysfunction in critically ill patients.

PMID- 11844986
TI  - Microdialysis in the intensive care unit: a novel tool for clinical investigation
      or monitoring?
AB  - Microdialysis is a minimally invasive tool that allows us to gain insight into
      metabolism at the tissue level. In human investigations, it can be safely
      performed in the brain (neurosurgical patients), skeletal muscle and adipose
      tissue. Basically, the technique allows interstitial concentrations of small
      solutes to be evaluated. Several limitations of the method and possible ways to
      circumvent them are indicated. Recent technical developments are reviewed. At
      present, this method is rarely used in metabolic monitoring of critically ill
      patients, but its potential applications are highlighted.

PMID- 11844987
TI  - Metabolic bases of amino acid requirements in acute diseases.
AB  - Acute diseases are characterized by a catabolic state, resulting in a negative
      nitrogen balance and muscle wasting. Increasing protein intake often proves to
      have little effect in limiting muscle protein loss. This suggests a qualitative
      inadequacy of the usual nutritional supports to meet the amino acid requirements
      of the critically ill patient. Therefore, it can be assumed that the additional
      intake of limiting amino acids would allow the sparing of muscle proteins. The
      aim of this review is to examine whether metabolic and kinetics studies using
      labelled amino acids can help identify the pathways activated in injury and their
      specific amino acid requirements. The kinetics of cysteine, arginine and
      glutamine, which are mainly cited as conditionally indispensable in stress
      situations, are presented. Moreover, amino acids can act as mediators or signal
      molecules and modulate numerous functions. The optimal conditions allowing the
      best expression of these activities are discussed.

PMID- 11844988
TI  - Dangers of growth hormone therapy in critically ill patients.
AB  - Prolonged length of stay is the major challenge for modern intensive care because
      of the associated morbidity and the impact on resource utilization. Severe trauma
      or infection is associated with a catabolic response, which is characterized by
      increased protein turnover and negative nitrogen balance. Severe catabolism leads
      to end-organ dysfunction and muscular weakness, prolonging the need for
      mechanical ventilation. Catabolism cannot be prevented with standard parenteral
      or enteral nutritional formulas. In order to prevent the complications of
      catabolism in intensive care patients, recombinant growth hormone has been
      applied as an experimental therapy for two decades in patients requiring
      parenteral nutrition and in patients with respiratory failure. Administration of
      recombinant growth hormone has resulted in positive nitrogen balance, and studies
      in mechanically ventilated patients suggest that it may shorten the need for
      ventilatory support. In contrast to the results of these relatively small
      studies, a recent multinational randomized controlled trial revealed that the
      administration of recombinant growth hormone (with doses 10-20 times higher than
      used for replacement therapy) increases mortality of critically ill patients. The
      excessive mortality in patients treated with recombinant growth hormone was
      related to infections and development of multiple organ failure, leading to the
      conclusion that administration of high doses of recombinant growth hormone cannot
      be recommended for critically ill patients. This review reinforces that
      conclusion.

PMID- 11844989
TI  - Hemoglobin switching and modulation: genes, cells, and signals.
AB  - A detailed understanding of hemoglobin production in erythroid cells is of
      fundamental clinical importance for the treatment of hemoglobinopathies. Several
      hundred scientific reports and dozens of reviews describe this intriguing topic
      of research. Early studies demonstrated the temporal nature of a hemoglobin
      switching phenomenon during development in the circulating erythrocytes of
      humans. The focus then shifted from descriptive to experimental analyses and
      model systems in an effort to define the switching mechanisms. The application of
      molecular biology in those experimental models has been a primary focus for the
      last two decades. Today, advances in the fields of stem cell biology and signal
      transduction are being integrated with those genetic studies. Genomic and
      proteomic approaches are also being developed to provide a more robust
      description of the biologic variables involved. This review highlights recent
      advances in erythroid genetics and cellular biology with an emphasis upon the
      modulation of fetal hemoglobin expression during the maturation of adult human
      erythrocytes.

PMID- 11844990
TI  - New insights into erythropoiesis.
AB  - Commitment of hematopoietic cells to the erythroid lineage involves the actions
      of several transcription factors, including TAL1, LMO2, and GATA-2. The
      differentiation of committed erythroid progenitor cells involves other
      transcription factors, including NF-E2 and EKLF. Upon binding erythropoietin, the
      principal regulator of erythropoiesis, cell surface erythropoietin receptors
      dimerize and activate specific intracellular kinases, including Janus family
      tyrosine protein kinase 2, phosphoinositol-3 kinase, and mitogen-activated
      protein kinase. Important substrates of these kinases are tyrosines in the
      erythropoietin receptors themselves and the signal transducer and transcription
      activator proteins. Erythropoietin prevents erythroid cell apoptosis. Some of the
      apoptotic tendency of erythroid cells can be attributed to proapoptotic molecules
      produced by hematopoietic cells, macrophages, and stromal cells. Cell divisions
      accompanying terminal erythroid differentiation are finely controlled by cell
      cycle regulators, and disruption of these terminal divisions causes erythroid
      cell apoptosis. In reticulocyte maturation, regulated degradation of internal
      organelles involves a lipoxygenase, whereas survival requires the antiapoptotic
      protein Bcl-x.

PMID- 11844991
TI  - Sickle cell vaso-occlusion: multistep and multicellular paradigm.
AB  - Sickle cell disease is characterized by recurrent, painful episodes and organ
      damage resulting from microvascular occlusion. Seminal studies performed 20 years
      ago revealed increased adherence of sickle erythrocytes to vascular endothelial
      cells. Subsequent work showed that these interactions were mediated by multiple
      adhesion pathways, but the relevance of these interactions has not been evaluated
      in vivo. Clinical data suggest that leukocytes may play a role, because
      leukocytosis correlates with clinical severity and early death, and
      administration of myeloid growth factors to patients can precipitate sickle cell
      crises. In addition, recent experimental data using intravital microscopy
      indicate that sickle erythrocytes can interact with adherent leukocytes in
      inflamed postcapillary and collecting venules. A novel multistep model for sickle
      cell vaso-occlusion is proposed in which endothelial activation is induced by
      sickle cells or secondary inflammatory stimuli and leads to the recruitment of
      adherent leukocytes. The resulting adherent leukocytes interact with circulating
      sickle erythrocytes, and this interaction impedes microvascular blood flow.
      Finally, irregularly shaped sickle cells become nonspecifically trapped,
      resulting in vaso-occlusion. The molecular mechanisms and requirements for the
      heterotypic interactions between erythrocytes and leukocytes are currently
      unknown and may involve further activation of adherent leukocytes or circulating
      erythrocytes. This model offers exciting new opportunities for therapeutic
      intervention and suggests a critical participation of adherent leukocytes in
      sickle cell vaso-occlusion.

PMID- 11844992
TI  - Sickle red cell dehydration: mechanisms and interventions.
AB  - A critical link between the single molecular defect in sickle cell anemia and the
      extensive pathology of this disease is the reversible increase in red cell
      membrane permeability generated by hemoglobin S polymers in the deoxygenated
      state. This permeability, usually described as P (sickle), triggers a chain of
      events in which two constitutive transporters of the red cell membrane become
      activated-the recently cloned intermediate conductance, Ca 2+ -sensitive K
      channel, and the electroneutral K:Cl cotransporter-leading to sickle cell
      dehydration. This article reviews knowledge of the dehydration mechanism,
      stressing the marked heterogeneity of dehydration rates in sickle cell
      populations, and discusses recent contributions to understanding of the function
      and regulation of P (sickle), Ca 2+ -sensitive K channel, and K:Cl cotransporter,
      and of therapies targeted at these transporters.

PMID- 11844993
TI  - Sickle cell disease in Africa.
AB  - Africa is the main birthplace of sickle mutations; the number of newborns
      affected by sickle cell disease is estimated at 200,000 per year. However,
      because of low family income and public health funding and, to a lesser extent,
      because of local beliefs about sickle cell disease, overall treatment of patients
      is still poor and, in some places, inadequate. Efforts to adapt therapeutic
      options and overcome difficulties are presented and analyzed.

PMID- 11844994
TI  - Sickle cell disease in India.
AB  - The clinical manifestations of sickle cell anemia in India seem to be milder than
      in Africa and Jamaica. Mostly homozygous sickle cell anemia patients seek
      treatment for vaso-occlusive crises, which have greatest incidence during the
      rainy season, followed by winter. It is interesting to note that both sickle cell
      anemia patients and carriers (heterozygotes) have iron deficiency. alpha
      Thalassemia is one of the major epistatic factors responsible for amelioration of
      the disease. Simple measures like vaccination in childhood, adequate oral intake
      of fluids with electrolytes during vaso-occlusive crises, and avoidance of
      exposure to extreme temperatures reduce the number of patients with vaso
      occlusive crises. Premarital counseling and prenatal diagnosis also help reduce
      the number of births of homozygous children.

PMID- 11844995
TI  - Pathophysiology of thalassemia.
AB  - Despite discoveries concerning the molecular abnormalities that led to the
      thalassemic syndromes, it still is not known how accumulation of excess unmatched
      alpha-globin in beta thalassemia and beta-globin in alpha thalassemia leads to
      red blood cell hemolysis in the peripheral blood, and in the beta thalassemias
      particularly, premature destruction of erythroid precursors in marrow
      (ineffective erythropoiesis). Oxidant injury may cause hemolysis, but there is no
      evidence that it causes ineffective erythropoiesis. Hemoglobin E/beta thalassemia
      is now a worldwide clinical problem. The reasons underlying the heterogeneity and
      occasional severity of the syndrome remain obscure. Ineffective erythropoiesis
      now appears to be caused by accelerated apoptosis, in turn caused primarily by
      deposition of alpha-globin chains in erythroid precursors. However, it is not
      clear how alpha-globin deposition causes apoptosis. The author uses new
      observations on the control of erythropoiesis to provide a framework for studying
      the enhanced thalassemic erythroid apoptosis.

PMID- 11844996
TI  - New insights into regulation of erythrocyte shape.
AB  - Two ideas explain the mechanism of shape regulation: the lipid bilayer coupled
      theory and the protein network scaffold theory. Recently, several important
      articles have been published on the former theory. However, many phenomena argue
      against the theory, including behavior of ghosts and triton shells, various types
      of manipulation of proteins, and fixation of the shape by the addition of large
      reagents outside the cell. Moreover, hereditary spherocytosis shows normal,
      uneven distribution of phospholipids, and hereditary and artificial defects of a
      membrane protein show spherocytes or elliptocytes. The liquid state of the lipid
      layer does not seem to support the shape or mechanical characteristics. On the
      other hand, all of these phenomena argue for the protein network scaffold theory.
      Characteristics of each protein and interactions among proteins are now being
      clarified, but this theory and the author's own ideas still lack decisive
      evidence.

PMID- 11844997
TI  - Band 3 anion exchanger and its involvement in erythrocyte and kidney disorders.
AB  - Recent developments in the structure of erythrocyte band 3 and its role in
      hereditary spherocytosis and distal renal tubular acidosis are described. The
      crystal structure of the N-terminal cytoplasmic domain provides a basis for
      understanding the organization of ankyrin and other peripheral membrane proteins
      around band 3. Band 3 also binds integral membrane proteins, including the Rh
      protein complex and CD47. Band 4.2 is important in these associations, which link
      the Rh complex to the skeleton. It is suggested that band 3 forms the scaffold
      for a protein assembly that could transduce signals from the cell exterior and
      modulate the transport and mechanical properties of the erythrocyte. The
      involvement of band 3 in distal renal tubular acidosis is reviewed. The article
      discusses a likely mechanism for dominant distal renal tubular acidosis in which
      associations between the normal and mutant protein alter the plasma membrane
      targeting of the normal protein in the kidney.

PMID- 11844998
TI  - Hydrolysis of erythrocyte proteins by proteases of malaria parasites.
AB  - During the intraerythrocytic phase of the life cycle, malaria parasites hydrolyze
      host proteins. Hemoglobin is processed into individual amino acids, which are
      used for parasite protein synthesis. Erythrocyte cytoskeletal proteins are
      cleaved during erythrocyte invasion and rupture. A number of plasmodial proteases
      that appear to be responsible for key cleavages of host proteins have recently
      been characterized. Hemoglobin hydrolysis appears to be mediated by acid
      cysteine, aspartic, and metalloproteases, and then a neutral aminopeptidase.
      Cysteine and aspartic proteases that hydrolyze hemoglobin can also cleave host
      cytoskeletal proteins, and these and additional proteases likely cleave the
      cytoskeleton to mediate erythrocyte rupture and invasion. Various protease
      inhibitors block parasite development, suggesting that key proteases may be
      appropriate chemotherapeutic targets. Recent advances in the characterization of
      plasmodial proteases should facilitate the analysis of the specific roles of
      these enzymes and expedite the progress of drug discovery efforts directed
      against them.

PMID- 11844999
TI  - Blood substitutes.
AB  - Blood substitutes are solutions intended to replace transfusion of banked red
      blood cells. Several variations of products based on either hemoglobin (animal or
      human) or perfluorocarbon emulsions are in advanced stages of clinical
      development. The need for such products is pressing as shortages of banked blood
      worsen and awareness of the dangers of blood transfusion increases. Animal and
      human studies with these cell-free oxygen carriers have led to new concepts of
      how oxygen is delivered to tissue and how the microcirculation is regulated.
      Although development of products is exciting and timely, understanding how they
      function to perfuse and oxygenate tissue could be at least as important. Because
      cell-free oxygen carriers will perfuse every organ of the body, their effects are
      far-reaching, and the transition from the laboratory to the bedside can be
      expected to be slow and deliberate. Comparison of oxygen carriers with more
      traditional starch-based products provides new insight into the interaction of
      oxygen transport, microvascular perfusion, and blood volume expansion.

PMID- 11845000
TI  - Molecular approaches to blood group identification.
AB  - Allogeneic barriers to transfusion are caused by differences between those
      portions of the donor and recipient genomes that define the antigenicity and
      immune response to the transfused cells. Historically, a blood group antigen was
      identified when an immune response (alloantibody) was detected by
      hemagglutination in the serum of a transfused patient. There has been an
      astounding pace of growth over the past two decades in the field of molecular
      biology techniques and even more recently in the understanding of the basis of
      many blood group antigens and phenotypes. Identification of blood group antigens
      can now be performed in genetic terms, and identification of blood group
      antibodies can be performed using molecular approaches. This knowledge is being
      applied to help resolve some long-standing clinical problems that cannot be
      resolved by classical hemagglutination. This article reviews knowledge of
      molecular approaches for identifying blood group antigens and antibodies as
      applied to transfusion medicine practice.

PMID- 11845001
TI  - Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines for
      chronic obstructive pulmonary disease.
AB  - The Global Initiative for Chronic Obstructive Lung Disease (GOLD) was developed
      recently to unify international efforts in the management of the disease. The
      most important GOLD objective is raising awareness that chronic obstructive
      pulmonary disease is an increasing health problem. The first step in the GOLD
      program was to prepare a consensus report, named "Global Strategy for the
      Diagnosis, Management, and Prevention of COPD," based on best-validated evidence
      and current pathogenetic and clinical knowledge. It encourages implementation of
      effective strategies for prevention, diagnosis, and management of the disease in
      all countries, and emphasizes the importance of renewed research initiatives.

PMID- 11845002
TI  - Genetic risk factors for chronic obstructive pulmonary disease.
AB  - Cigarette smoking is clearly the major risk factor for chronic obstructive
      pulmonary disease. However, only a minority of cigarette smokers develops chronic
      obstructive pulmonary disease, indicating that other factors are involved. Family
      and twin studies suggest that at least some of those factors are genetic. This
      article reviews the genes investigated as potential risk factors for this
      disease, focusing on the recent literature. The only established genetic risk
      factor for chronic obstructive pulmonary disease is homozygosity for the Z allele
      of the alpha1 -antitrypsin gene. There is increasing evidence that heterozygotes
      for the Z allele may also be at increased risk. Variants in genes involved in
      xenobiotic metabolism, antioxidation, and the inflammatory response have also
      been associated with chronic obstructive pulmonary disease. Thus, the genetic
      basis for chronic obstructive pulmonary disease has begun to be elucidated, and
      it is likely that several genes will be implicated in the pathogenesis of this
      disease.

PMID- 11845003
TI  - Chronic obstructive pulmonary disease in the United Kingdom: trends in mortality,
      morbidity, and smoking.
AB  - Current trends in chronic obstructive pulmonary disease (COPD) in the UK differ
      from those in many other countries because, in the past, COPD was much more
      common than in other countries undergoing a smoking epidemic at the same time,
      and peak cigarette consumption in men and women occurred more 25 years ago. Male
      mortality from COPD has been falling for 30 years, while female mortality has
      risen steadily during the same period. A strong socioeconomic gradient in
      morbidity and mortality persists. Emergency hospital admissions for exacerbations
      and home oxygen account for a large proportion of the healthcare costs.

PMID- 11845004
TI  - Chronic obstructive pulmonary disease in Japan.
AB  - In Japan, the term chronic obstructive pulmonary disease (COPD) has only recently
      come to be used as it is in Western countries, especially with respect to its
      classification as a tobacco-related disease. The disease, COPD, did not appear in
      Japanese government statistics until 1995. The main reason for the nearly 20-year
      lag behind the West in recognizing this disease was the small number of COPD
      cases caused by smoking. Cigarette consumption in Japan increased with the
      increase in personal income that accompanied rapid ecomomic growth from 1955 to
      1974. Since approximately 1980, the number of deaths caused by COPD (emphysema)
      started increasing. Although cigarette consumption stopped increasing after 1995,
      COPD (emphysema) mortality is still increasing as a repercussion of the earlier
      increases of cigarette consumption. However, the number of COPD patients and the
      scale of medical expenditure for COPD in Japan is somewhat smaller than in
      Western countries.

PMID- 11845005
TI  - New therapeutic drugs in the management of chronic obstructive pulmonary disease.
AB  - Chronic obstructive pulmonary disease remains a major health problem for which
      new and improved treatments are desperately needed. Recent trials strongly
      suggest that treatments are improving. Longer-acting bronchodilators will be more
      convenient and may have additional advantages. Combinations of bronchodilators
      may offer additive effects and, possibly, synergies. Inhaled glucocorticoids,
      although unable to alter the loss of forced expiratory volume in 1 second when
      used alone, may reduce exacerbation frequency and health status deterioration and
      improve mortality. These clinically meaningful goals represent end points not
      previously targeted in chronic obstructive pulmonary disease drug development.
      Moreover, inhaled glucocorticoids may offer benefits in combination with long
      acting beta-agonists. Finally, new classes of agents such as the
      phosphodiesterase inhibitors are on the horizon. The prospect for better
      treatment of chronic obstructive pulmonary disease looks brighter than ever.
      Caution is required, however. Much of the excitement has been generated by small
      studies, presented only in abstract form, and as yet unpublished work.
      Therapeutic recommendations will require publication of appropriately designed
      and adequately powered clinical trials.

PMID- 11845006
TI  - Bronchiolitis: update 2001.
AB  - In this review, reports from last year on the following topics are summarized:
      (1) reviews of bronchiolitis in infants; respiratory syncytial virus (RSV)
      associated illness, including possible viral mechanisms of alteration of airway
      function and results of an epidemiologic study of bronchiolitis-associated
      mortality. Studies evaluating (2) the use of serum eosinophilic cationic protein
      as a marker for development of subsequent persistent wheezing infants; (3)
      parental bronchial responsiveness as an indicator of genetic susceptibility to
      acute bronchiolitis; (4) prophylactic use of monoclonal antibody (Palivizumab) to
      control an outbreak of RSV in a hospital nursery; (5) a controlled clinical trial
      of ribaviron in acutely ill children; (6) reports of new associations with
      bronchiolitis obliterans organizing pneumonia (BOOP); (7) case reports of use of
      methotrexate as an alternate to corticosteroids in treatment of BOOP; (8) a newly
      described entity, eosinophilic bronchiolitis.

PMID- 11845007
TI  - Review: occupational and environmental lung disease.
AB  - Occupational and environmental lung disease is a vast topic. Therefore, this
      review focuses on areas that represent new clinical insights that have not been
      addressed recently in Current Opinion in Pulmonary Medicine. The topics are
      considered important for the future and emphasize diseases that strike large
      numbers of people or exposures that affect large segments of the population. This
      review highlights literature published between the years 2000 to 2001 related to
      air pollution, occupational asthma, lung diseases in agricultural workers, nylon
      flock workers lung disease, pneumoconiosis, and environmental exposure to biomass
      smoke, including environmental tobacco smoke. These publications highlight the
      changing world of occupational and environmental lung diseases. Traditionally,
      this field dealt with chronic diseases caused by very high levels of exposure to
      materials that affected virtually all workers to a similar degree. Disease could
      be recognized readily by characteristic symptoms, signs, and radiographic
      abnormalities. Dose-effect relationships were usually clear, and the solution to
      disease was generally to limit exposure for all workers. This approach served
      well for conditions such as coal workers pneumoconiosis or toxic responses to
      chlorine gas. The new world of occupational and environmental lung diseases often
      involves low levels of exposure to complex mixtures of materials that produce
      nonspecific or intermittent symptoms in a subgroup of exposed individuals.
      Interactions between genetic susceptibility, concomitant tobacco smoke exposure,
      and co-morbid diseases hugely complicate both diagnosis and prevention. New
      tools, and possibly new thought paradigms, are needed to detect, treat, and
      prevent occupational and environmental lung diseases in a changing world.

PMID- 11845008
TI  - Recent advances in diagnosis and management of chronic bronchitis and emphysema.
AB  - Chronic obstructive pulmonary disease is a progressive inflammatory disease of
      the airways and lung parenchyma. Expiratory airflow limitation is the hallmark of
      chronic obstructive pulmonary disease. It is a significant cause of morbidity and
      mortality in the United States and worldwide and results in a large consumption
      of health care resources. Unfortunately, despite efforts to curb this disease,
      its prevalence is increasing. The diagnosis is usually made when the patient
      complains of dyspnea on exertion; by this time, irreversible structural damage to
      the lung has already occurred. Given the nonspecific symptoms of the disease and
      the inability to effectively treat and reverse the damage, it is essential to
      diagnose the disease in its early stages and take the necessary preventive
      measures, thus avoiding disability or death. This review summarizes the latest
      developments in the diagnosis and management of chronic obstructive pulmonary
      disease. The first half of the review discusses functional, radiographic,
      biochemical, and cellular/histopathologic issues in the diagnosis of chronic
      obstructive pulmonary disease. The second half focuses on the current
      pharmacologic and nonpharmacologic advances in chronic obstructive pulmonary
      disease, including the role of respiratory support and surgical treatment. Based
      on the research on the cellular mechanisms of chronic obstructive pulmonary
      disease, the review also makes a reference to novel and experimental therapies
      for chronic obstructive pulmonary disease.

PMID- 11845010
TI  - An update on the relationship between occupational factors and osteoarthritis of
      the hip and knee.
AB  - This study reviews articles published in 2000 and 2001 about occupational
      physical activities as risk factors for osteoarthritis (OA) of the knee and hip.
      Six studies were identified in MEDLINE and EMBASE; five case-control studies and
      one cross-sectional study. Criteria for OA were: (on the waiting list for) joint
      replacement or (symptomatic) radiologic OA. Exposure was assessed by structured
      interviews or self-administered questionnaires. Job titles or details on specific
      physical activities were used as determinants. The authors determine that
      information bias and nondifferential misclassification, with respect to
      occupational risk factors, cannot be excluded. Relevant confounding factors were
      adequately taken into account. Even though response rates were high, nonresponse
      bias may still have an influence, although its impact cannot be assessed
      accurately. Within these constraints the studies gave further evidence to support
      the role of jobs and occupational physical activities on the occurrence of OA.

PMID- 11845011
TI  - Influence of cigarette smoking on disease outcome in rheumatoid arthritis.
AB  - Cigarette smoking is a well-known risk factor for rheumatoid arthritis. However,
      the influence of smoking on disease outcome has only been investigated very
      recently, and the data are not clear-cut. Smoking has a number of important
      effects on the immune system and sex hormones that may influence disease
      pathogenesis. Smoking has also been shown to affect disease outcome in other
      inflammatory diseases. The major focus of this review is to explore the
      relationship between smoking and severity of rheumatoid arthritis in detail.

PMID- 11845012
TI  - Epidemiology of psoriatic arthritis.
AB  - Research into psoriatic arthritis continues to be hampered by the lack of a
      validated case-definition. There may be progress toward consensus with a new data
      derived diagnostic classification criteria set recently reported and a current
      international project aiming to firmly validate criteria. Statistical techniques
      such as latent class analysis may permit a comparison of the accuracy of
      competing criteria sets, in the absence of a gold standard for diagnosis. Genetic
      studies are inconclusive, but ethnic differences in disease expression suggest a
      definite genetic role. Recent community-based research suggests an incidence rate
      of about 6/100,000 per annum, and a prevalence of about 1/1000. Clinic-based
      disease may be associated with increased mortality, whereas community based
      disease is not. The development of internationally accepted criteria for the
      diagnosis of psoriatic arthritis will be a major impetus towards research into
      this complex disease.

PMID- 11845013
TI  - Why do patients with chronic musculoskeletal disorders consult their primary care
      physicians?
AB  - Symptoms are a daily occurrence in the lives of most people, and many do not
      consult their doctors for their clinical complaints. Information on the frequency
      of musculoskeletal disorders and on healthcare utilization patterns can be
      obtained from population surveys or from records of visits to primary care
      physicians. A decision to consult a primary care physician for musculoskeletal
      disorders is not based simply on the presence or absence of physical symptoms,
      but also involves a complex mixture of social and psychological factors.

PMID- 11845014
TI  - Many faces of the minimal clinically important difference (MCID): a literature
      review and directions for future research.
AB  - The minimal clinically important difference (MCID) for an instrument is a much
      sought after, but elusive figure. In this review we will highlight new findings
      in this area, including taxonomy of MCID, methods used to ascertain MCID, the
      perspective taken for evaluating importance, and other sources of variation for
      MCID values. In the end we believe the MCID will be a context-specific value
      rather than a fixed number. The review highlights the need to do methodological
      research in this area, especially concurrent comparisons between approaches, or
      across different patient groups. There are many faces to the MCID, it is not a
      simple concept, nor simple to calculate.

PMID- 11845015
TI  - Coronary artery disease and rheumatoid arthritis.
AB  - Patients with rheumatoid arthritis (RA) have a reduced life expectancy when
      compared with the general population. Cardiovascular death is considered the
      leading cause of mortality in patients with RA; it is responsible for
      approximately half the deaths observed in RA cohorts. The prevalence of
      cardiovascular comorbidity is difficult to assess accurately, because
      cardiovascular disease (CVD) has a tendency to remain silent in the rheumatoid
      patient. It is not clear why rheumatoid patients have higher rates of coronary
      disease. Traditional cardiovascular risk factors do not seem to be wholly
      responsible for the increased cardiovascular risk. Novel cardiovascular risk
      factors, including inflammatory markers, have been identified over the past few
      years. It may be that these new cardiovascular risk factors are responsible for
      accelerating coronary heart disease in patients with RA. This article reviews
      recent literature relating to the epidemiology of cardiovascular disease in the
      context of RA.

PMID- 11845016
TI  - Cost of illness studies in rheumatic diseases.
AB  - Knowledge about the economic burden of rheumatic diseases has progressed during
      recent years. In addition to the increasing number of studies published, the
      Economics Working Group of the Outcome Measures in Rheumatoid Arthritis Clinical
      Trial (OMERACT) Conference has produced substantial work to improve
      methodological standards for the economic evaluation of rheumatic diseases. Some
      of their preliminary results are presented in this review. Recent data have
      confirmed two main conclusions of previous studies: the total economic burden of
      rheumatic diseases is often more substantial than other chronic conditions,
      including cardiovascular diseases and cancer; and the impact of the disability
      caused by musculoskeletal diseases is significant on both direct (long-term care
      in osteoporosis for example) and indirect costs (productivity loss in chronic
      patients). Besides that, cost-effectiveness studies have provided valid
      information to improve disease management, especially for patients with
      rheumatoid arthritis or chronic low back pain.

PMID- 11845017
TI  - Biology and biomechanics.
AB  - Increased participation by the general population in athletic activities leads to
      increased trauma to bones, joint surfaces, and soft tissues. Management and
      treatment of these injuries has significantly improved over the past few decades.
      The application of knowledge gained from basic science research in biology and
      biomechanics has continuously contributed to that. Biological advances have been
      made in the field of gene therapy, cell therapy, and tissue engineering.
      Certainly, the greatest focus is bone and cartilage research that will lead to
      improved fracture repair in the traumatic injured population, as well as
      prevention of early osteoarthritic changes in the injured athletic population. In
      biomechanical research, contributions have been made to further understand
      kinematic behavior of joints that will lead to improved ligament reconstruction
      techniques and rehabilitation regimens. Various fixation techniques and several
      different ligament reconstruction techniques have been studied and validated. In
      the future, improved understanding of ligament healing, graft incorporation, and
      revascularization will lead to improved outcome of surgical reconstruction
      techniques in orthopaedic sports medicine. Exciting research has been performed
      over the past years and will be reviewed in this article.

PMID- 11845018
TI  - Chondral injuries.
AB  - Chondral injures are present in up to 10 to 12% of all individuals. When
      symptomatic, chondral lesions manifest in knee pain, swelling, and loss of
      function. Cartilage loss may be partial or complete, and it may affect one or
      multiple locations. The natural history of untreated lesions most likely results
      in increased disability and progression of cartilage loss. Lesions are classified
      according to location, depth, and size. Nonsurgical treatment modalities include
      oral medications, injections, bracing, or physical therapy. Surgical treatment
      ranges from arthroscopic debridement to implantation of autologous chondrocytes
      beneath a periosteal patch covering the lesion. The patient's symptoms, age,
      activity level, and lesion characteristics must be considered and matched with a
      suitable procedure.

PMID- 11845019
TI  - Posterior cruciate ligament injuries.
AB  - There is a relative lack of research and literature investigating injuries to the
      posterior cruciate ligament (PCL), despite the fact that it is an important knee
      stabilizer. The PCL is injured less frequently than other knee ligaments, and the
      mechanism is usually a direct blow to the anterior aspect of a flexed knee.
      Clinical examination of a PCL-deficient knee may reveal a positive posterior
      drawer, quadriceps active test, or Godfrey test. Chronic PCL insufficiency may
      result in patellofemoral and medial compartment degenerative arthritis.
      Controversy exists over the treatment of PCL injuries, with the exception of
      surgical treatment of avulsion fractures. Many believe that isolated PCL injuries
      of any grade may be treated nonoperatively with an excellent outcome. However,
      PCL reconstruction is recommended for patients with grade III PCL injuries who
      remain symptomatic despite adequate physical therapy or if the PCL deficiency is
      part of a multiple-ligament knee injury.

PMID- 11845020
TI  - Shoulder injuries in the athlete.
AB  - Shoulder injuries are common in the athletic population. Injuries can be a result
      of repetitive overhead use or from direct trauma. Common injury sites include the
      rotator cuff, glenohumeral joint, acromioclavicular joint, biceps tendon,
      scapulothoracic articulation, and sternoclavicular joint. The identification,
      physical exam, and treatment options of these conditions will be discussed.

PMID- 11845021
TI  - Elbow injuries.
AB  - The elbow is a commonly injured joint, yet physicians may be less comfortable
      treating injuries to the elbow compared with knee and shoulder injuries. Common
      injuries involving the elbow are tendinosis, instability, tendon ruptures,
      osteochondritis dissecans, and fractures. Tendinosis is a common overuse injury
      and may occur on the lateral, medial, or infrequently, the posterior side of the
      elbow. Injury to the medial or lateral ulnar collateral ligaments may result in
      instability. Repetitive trauma from overuse is the most common etiologic factor
      in athletes. Distal biceps and triceps tendon injuries may result in elbow
      disability in active individuals. Partial tears are more difficult to diagnose
      than complete ruptures. Osteochondritis dissecans of capitellum affects
      adolescents involved in overhead throwing athletics. Fractures about the elbow
      most commonly involve the radial head in adults, and the distal humerus in
      children. Athletes are prone to elbow injuries resulting from both overuse and
      acute trauma. Our purpose is to describe the diagnosis and treatment of these
      common elbow injuries in athletes of all ages.

PMID- 11845022
TI  - Neuromuscular contributions to anterior cruciate ligament injuries in females.
AB  - Although anterior cruciate ligament (ACL) injuries are not gender specific, they
      do occur at a significantly greater rate in females. Biomechanical and
      neuromuscular deficits in females have been documented as factors contributing to
      ACL injuries, however little research has been conducted in the area of
      preventative training programs to improve these deficits. This article will
      describe the biomechanical and neuromuscular factors that contribute to ACL
      injuries in females, and provide a foundation from which preventative training
      programs should be designed.

PMID- 11845023
TI  - The future of anterior cruciate ligament surgery.
AB  - Future anterior cruciate ligament surgery techniques will evolve from emphasizing
      the technical factors involved in successful ligament reconstruction to
      emphasizing the biomechanical, neuromuscular, and biologic factors, which will
      enhance healing. Advances in computer and robotic technology will help the
      surgeon perform anterior cruciate ligament reconstruction. The importance of the
      anterior cruciate ligament and its relationship with other anatomic and
      neuromuscular structures of the knee has been well researched over the past
      decade; the next decade will combine this knowledge with technological and
      biological advancements.

PMID- 11845024
TI  - [Ultrasonic assessment of thyroid nodules, and iodine status of French adults
      participating in the SU.VI.MAX study].
AB  - Thyroid nodules were assessed by ultrasound in 3 621 presumably healthy free
      living French subjects participating in the SU.VI.MAX cohort (2 160 females aged
      35-60 years and 1 461 males aged 45-60 years). Urinary iodine was measured in all
      participants in random morning urine samples. Nodular thyroid structures ranging
      from 3 mm to 57 mm in diameter were found in 14.5% of the population, without
      significant differences between regions in the different age and sex groups.
      Single nodules and multiple lesions were found in, respectively, 9.7% and 3.1% of
      the subjects. In females, nodules increased from 12.9% to 19.2% between 35-45
      years and 45-60 years, respectively (p<0.001). Thyroid nodularity was more
      frequent among women aged 45-60 years than among men of those ages (19.2% vs.
      11.0%, p=0.001). Descriptive data provided by ultrasound differentiated the
      nodules into solid (43.4%), cystic (38.4%), and mixed solid-cystic (18.2%). Most
      solid thyroid nodules, 76.1%, were hypoechoic, while 16.6% were iso-, and 7.3%
      were hyperechoic. The median of iodine concentrations (n=3 276) was 8.0
      microgram/100 ml, with 19.4% of the samples being<5 microgram/100 ml. Median
      iodine concentrations displayed wide regional variations, with values
      significantly higher in residents of western regions than among those living in
      the eastern areas (p<0.001), independently of age and sex. No relationship was
      found between prevalence of nodular thyroid structure and the state of borderline
      iodine status observed in France.

PMID- 11845025
TI  - [Prolonged treatment with recombined growth hormone improves bone measures: study
      of body composition in 21 deficient adults on treatment].
AB  - Adult growth hormone deficiency is characterized by changes in body composition:
      increase in total fat, decrease in lean mass and osteopenia, with a fall in Bone
      Mineral Content (BMC) and in Bone Mineral density (BMD) leading to a rise in risk
      of fracture. We have analyzed the changes in body composition in 21 adults
      treated from 9 to 78 months, by dual X-RAY absorptiometry (DEXA). We've
      demonstrated a gain in bone mass and density, particularly of axial skeleton; a
      latence of minimum 12 months has been necessary to objective these changes. The
      balance of fat and lean mass has been poorly modified by treatment except for the
      lean mass of the trunk, which is significantly increased. We think that the usual
      doses of rGH, based on IGF-1 level, are perhaps underestimated.

PMID- 11845026
TI  - [Problems in the management of thyrotoxicosis in Black Africa: the Tongolese
      experience].
AB  - In black Africa, and particularly in Togo, management of thyreotoxicosis is not
      simple. The intervention of several specialists and effective patient
      collaboration is needed. In a majority of cases, the patient's apprehensions,
      financial problems, and taboos prevent correct management. We report 30 cases of
      thyreotoxicosis in 82 patients with thyroid disease seen over a 5-year period in
      the Internal Medicine and Cardiology Department of the Lome teaching hospitals.
      Graves' disease was the most frequent (83.33%), followed by multinodular goiter
      (10%) and toxic nodule (6.67%). Diagnosis was strictly clinical in 53.33% of the
      cases. The main complication was cardiothyreosis in 46.67% of the patients. Drug
      treatment was used. Short-term results (4 - 6 weeks) was favorable in 96.67% of
      the cases. A percentage (65.41%) were lost to follow-up after discharge. The main
      impairment encountered for the management of thyreotoxicosis was financial and
      economical difficulties not specific to the disease. Other problems included the
      lack of diagnostic and therapeutic means and insufficient cooperation between the
      surgeon, the cardiologist and the endocrinologist.

PMID- 11845027
TI  - [Isolated pelvic metastasis of thyroid cancer].
AB  - Thyroid cancer rarely metastasizes to the pelvis. We report a case where the
      metastasis was found two years before the thyroid cancer. Treatment included
      initial surgery with resection of the metastatic tumor and reconstruction of the
      acetabulum with bone cement, and secondly total thyroidectomy, node dissection
      and I131. Surgical treatment of locoregional recurrence had no influence on the
      clinical course leading to the patient's death. Early diagnosis of unique
      metastasis of a thyroid cancer is important in terms of prognosis and quality of
      life. This case is exceptional due to the unique bone metastasis and treatment
      options for acetabular metastases. Therapeutic options should be adapted
      according to algorithms reported in the literature.

PMID- 11845028
TI  - [Obesity, diabetes mellitus, and gas gangrene: a major therapeutic challenge].
AB  - Soft tissue infections are uncommon but prognosis is severe (20 to 50%).
      Management consists in surgical debridement, antibiotic therapy against anaerobic
      and aerobic bacteria, and appropriate intensive care. When available, hyperbaric
      oxygen therapy is an integral part of the treatment. We report the case of 56
      year-old female patient with diabetes (150 kg) was hospitalized in our unit a few
      days after surgical treatment of a buttocks abscess for clinical signs of
      peripheral gas gangrene. Surgical exploration showed necrotizing soft tissue
      infection with fasciitis. Adequate therapy using antibiotics, surgery daily and
      hyperbaric oxygen was given. Therapy had to be adapted to the patient's obesity.
      Outcome was good with recovery and few sequelae, allowing transfer to a medical
      ward.

PMID- 11845030
TI  - [Perrault's syndrome: two cases].
AB  - Perrault's syndrome is an autosomal recessive ovarian dysgenesis associated with
      sensorineural deafness. We report two cases in sisters issuing from consanguinous
      parents. Aged 16 and 21 years, both patients present the two cardinal symptoms of
      the syndrome. Magnetic resonance imaging in the second sister showed high
      intensity signals in the periventricular and subcortical white substance and in
      the central ovale, suggestive of cerebral leucodystrophy. This element may be one
      of a wide spectrum of neurological symptoms found in Perrault's syndrome. The
      discovery of the causal genes may allow better understanding of the biomolecular
      mechanisms involved in gonad and sensorineural differentiation.

PMID- 11845029
TI  - [Pseudohypoparathyroidism or hypoparathyroidism? A misleading clinical
      presentation].
AB  - We report the case of a 27-year old woman who presented hypocalcemia and
      hyperphosphoremia during her first pregnancy. Her phenotype was in favor of
      Albright's hereditary osteodystrophy: short stature, obesity, round face,
      brachymetacarpy and mental retardation. However, the diagnosis of pseudohypopara
      thyroidism type Ia was ruled out due to low PTH level (10 pg/ml). The patient's
      22q11 microdeletion was suspected and identified because of the association of
      severe neonatal hypocalcemia, abnormal face and renal malformation in her
      children. Deletion 22q11 leads to various syndromes, including Di George
      syndrome, also referred to as CATCH 22 syndrome (Cardiac defect (C), Abnormal
      face (A), Thymic hypoplasia (T), Cleft palate (C) and Hypocalcemia (H)).
      Retrospectively, the patient presented with symptoms suggestive of CATCH 22:
      abnormal face, hypernasal voice suggestive of velopharyngeal insufficiency,
      mental retardation, recurrent otitis in childhood. It is also noteworthy that
      there was an idiopathic thrombocytopenic purpura. In conclusion, while the
      phenotype was suggestive of Albright's hereditary osteodystrophy, the
      constatation of a low PTH level would cast doubt on this diagnosis. Furthermore,
      the 22q11 microdeletion should be searched by FISH (Fluorescence In Situ
      Hybridization) in all patients with hypopara thyroidism of unknown origin, even
      in the absence of cardiac malformations. Finally, it seems that patients with
      CATCH 22 would be predisposed to auto-immune disease as a result of thymic
      dysfunction.

PMID- 11845031
TI  - Lingual thyroid. A case report.
AB  - We describe an unusual clinical case in which a non functional cervical thyroid
      coexisted with a functional ectopic lingual thyroid. A twenty-year-old woman was
      referred for hypothyroidism treated with L-thyroxin related to a basilingual
      tumor diagnosed 8 years previously. Oropharyngeal examination showed a spherical
      basilingual tumor 2.5 cm in diameter. Laboratory findings during treatment with
      50 microgram of L-thyroxin daily showed: TSH 6,280 microIU/ml (N: 4,4 to 3.6),
      FT3 4,2 pmol/l (N: 3.3 to 5.1), and FT4 15.4 pmol/l (N: 10,5 to 25,5).
      Antithyroid antibodies were absent. Cervical ultrasonography showed a small
      hypoechogenic, heterogeneous orthotopic thyroid gland confirmed by cervical
      computed tomography thyroid. An I(123) scan revealed uptake above the chin on the
      profile, and no significant uptake is the area of the normal thyroid. The lack of
      iodine uptake by the cervical thyroid remains unexplained. In conclusion, this
      report of an ectopic thyroid location in unusual because of the coexistence of
      non functional cervical thyroid and of a partially functional lingual thyroid
      tissue. The pathogenesis of this association remains unclear.

PMID- 11845033
TI  - [Malformations of the ear in the CHARGE syndrome].

PMID- 11845032
TI  - [Hormonal perturbations in fibromyalgia].
AB  - Fibromyalgia is a syndrome characterized by chronic musculoskeletal pain and
      fatigue without biological detectable disturbances. The mechanisms of this
      disease are unknown. It has been postulated that it can be the consequence of a
      chronic stress mediated mainly through the hypothalamo-pituitary-adrenal axis and
      the sympathetic nervous system. These fields have been extensively studied.
      Results were scattered and non convincing. A reduction of growth hormone and IGF
      1 levels described in a third of patients has led to a double blind random
      clinical trial with biogenetic growth hormone. Results were equivocal . Other
      hormonal systems are grossly normals and circadian rhythms are unaltered. Despite
      some arguments in favour of a CRH neurons hyperactivity, these results are not
      able to consolide a particular physiopathological mechanism and to argument for a
      new therapeutic approach. Many of the abnormalities may be the consequence of
      psychological disturbances.

PMID- 11845035
TI  - [Tympanostomy tube otorrhea: microbiological epidemiology, pathogen
      susceptibility to local antibiotics and bactericidal power of the rifamycin
      olfloxacin combination].
AB  - OBJECTIVE: We studied the microbiological epidemiology of tympanostomy tube
      otorrhea, rifamycin and ofloxacin sensitivity of pathogens isolated from these
      otorrheas, and the bactericidal power of the rifamycine-ofloxacin combination.
      MATERIAL AND METHODS: A prospective study was conducted in 1997 with cultures of
      otorrhea aspirates, in vitro study of pathogen resistance to rifamycin and
      ofloxacin, bacteriocidal study of the rifamycin-ofloxacin combination. RESULTS:
      One hundred eight aspirates were obtained from 98 children (mean age 5 years).
      Ten aspirates were sterile, 32 had more than one pathogen. The more frequent
      pathogens were Pseudomonas aeruginosa (Pa) (n=35), Staphylococcus aureus (Sa)
      (n=27), Haemophilus influenae (Hi) (n=12) and Streptococcus pneumoniae (Sp)
      (n=9). All Hi, all Sp, 86.3% of the Sa (MIC(90) 0.25 mg/l) and none of the Pa
      were rifamycin sensitive. All Hi, 97.7% of the Pa (MIC(90) 0.5 mg/l), 73,1% of
      the Sa (MIC(90) 0.24 mg/l) and none of the Sp were ofloxacin sensitive. The
      rifamycin-ofloxacin combination led to a 4 log CFU/ml decrease in 6 hours for Sp,
      and in 24 hours for Pa, Hi and Sa. CONCLUSION: The rifamycin-ofloxacin
      combination is bactericidal for bacteria causing tympanostomy tube otorrhea. Otic
      drops with this combination should be considered as the first line treatment for
      such otorrhea.

PMID- 11845036
TI  - [Predictive factors of outcome in 220 ossiculoplasties in adults].
AB  - OBJECTIVE: To define factors predictive of outcome after ossiculoplasty in
      adults. MATERIAL AND METHODS: From 1992 to 1998, 220 ossiculoplasties were
      performed for chronic otitis media in 200 patients (100 men and 90 women),
      average age 53 years, age range 17 - 82 years. Ninety-four patients (47%) had not
      undergone prior surgery (99 ossiculoplasties) and 106 (53%) underwent revision
      procedures (121 ossiculoplasties). Average follow-up was 20 months. All patients
      were reexamined at consultations 3 and 12 months after surgery and 100 patients
      (50%) were reexamined at two years. The operations were classified in type II
      tympanoplasty when the patient presented a normal stapes (n=120), and a type III
      tympanoplasty when the stapes arch was absent (n=100). Perforations (n=200) were
      repaired by temporal aponeurosis in 160 cases (80%) and a tragal perichondrium in
      40 cases (20%). The materials used included 23 incus autografts (10%), 105
      hydroxyapatite composite Goldenberg prosthesis (48%), 55 all-hydroxyapatite Xomed
      prosthesis (25%) including 20 covered with a thinned tragal cartilage, 19 teflon
      Klein prosthesis (9%), 12 Ionos prosthesis (5%) and 6 Malleus prosthesis (3%).
      The results were analyzed from the microscopic aspect and audiometric data for
      frequencies 0,5 to 3 KHz. RESULTS: Twenty prosthesis luxed or extruded (9%)
      within an average of 6 months, 15 (12.4%) after a revision procedure and 5 (5%,
      p<0,05) after an initial procedure. Fifteen perforations (15/200, 7.5%) occurred,
      9 with temporal aponeurosis grafts (9/160, 5.6%) and 6 with perichondrium grafts
      (6/40, 15%, NS). The residual air-bone gap (ABG) was equal to 23 +/- 12,5 dB with
      57% of ABG<20 dB at 12 months follow-up. The gain in air conduction was 14 +/-
      16,5 dB and the change in air-bone gap 13 +/- 12,3 dB. Some factors could
      significantly improve functional results: presence of the stapes arch (n=120,
      p<0,05), first-intention procedure (n=99, p<0,05), and use of all-hydroxyapatite
      prosthesis in type II (p<0,05) or type III tympanoplasties. CONCLUSION:
      Ossiculoplasty with all-hydroxyapatite prosthesis produced satisfactory results
      in type II or III tympaonoplasties.

PMID- 11845037
TI  - [Sinus-nasal polyposis: one-year outcome after endoscopic sinus surgery followed
      by topical corticosteroid therapy in 72 patients].
AB  - Nasal polyposis (NP) is considered as an inflammatory disease for which first
      line therapy is topical and/or oral corticosteroid. In this paper we attempted to
      determine the efficacy of endoscopic endonasal surgery followed by topical
      corticoid in 72 adults suffering from bilateral NP refractory to corticosteroid
      therapy and to delineate the clinical characteristics of this cohort of patients.
      NP was confirmed endoscopically and with computed tomography. Visual analog scale
      for the subjective evaluation and endoscopic examination of the paranasal
      cavities for the objective evaluation were obtained 3 and 12 months
      postoperatively. Endoscopic endonasal surgery was based on a radical removal of
      the NP with wide opening of all the sinuses in the vast majority of the cases.
      Topical corticoid therapy was started 2 months after surgery. Clinical
      characteristics of the 72 patients revealed: 29.2% of coexisting allergy; 34.7%
      of coexisting asthma; 19.4% with food and/or aspirin intolerance. Anterior and
      posterior ethmoid sinus and maxillary sinus were the most affected sinuses. 53.5%
      of our patients presented a stage II. One year after surgery we observed that
      59.1% of our patients revealed a marked decrease of their symptoms with no polyp
      on nasal endoscopic evaluation, that 28.8% revealed a marked decrease of their
      symptoms with recurrence of the NP on nasal endoscopic evaluation and that 12.1%
      presented moderate to severe symptoms with recurrence of NP on nasal endoscopic
      evaluation. Based on this experience, we think that endoscopic endonasal surgery
      will continue to play an important role in the management of NP when the patient
      becomes refractory to corticoid.

PMID- 11845038
TI  - [Treatment of subglottis stenosis in children by cricotracheal resection].
AB  - Fifty-eight infants and children with a severe subglottic stenosis underwent a
      partial cricotracheal resection with primary thyrotracheal anastomosis. There
      were 2 grade II, 40 grade III, and 16 grade IV stenoses according to the Myer
      Cotton classification. A 100% subglottic lumen was formed in 34 cases and a
      better than 80% lumen in 23 cases. Fifty-four of the 58 (93%) patients are
      presently decannulated; one patient sustained a complete restenosis and three
      patients with a better than 80% subglottic airway still await decannulation for
      the following reasons: severe tracheomalacia, bilateral cricoarytenoid joint
      fixation and laryngeal malformation with fusion of the vocal cords in each case
      respectively. Forty-four patients have no exercise intolerance, 8 live fully
      normally but present a slight exertional dyspnea, one patient with a laryngeal
      malformation is decannulated but suffers from a severe exertional dyspnea, and 4
      patients are still not decannulated. The voice is normal in 20 cases, a slight
      dysphonia is present in 17, a moderate to severe dysphonia in another 17 and 4
      patients are still not decannulated.

PMID- 11845039
TI  - [Wegener's granulomatosis involving head and neck: retrospective analysis of 16
      patients].
AB  - Based on a retrospective analysis of patients with Wegener's granulomatosis (WG),
      the aim of our study was to compare our finding with those previously reported in
      the literature. We also reviewed the characteristic features of WG, particularly
      otorhinolaryngology features. Sixteen consecutive patients were followed over a
      period of 23 years. There were 8 men and 8 women, all Caucasians, aged between 13
      and 74 years (mean 42 years). Initial ENT signs and symptoms were observed in
      62.5% of the cases, and occurred in 94% during disease progression with
      predominant rhino-sinusal (75%) and otological (38%) or laryngotracheal (25%)
      localizations. Later, the disease primarily affected the lower respiratory tract
      (87.5%) and the kidneys (50%). Articular (40%), ocular (25%), cardiovascular
      (25%), neurological (25%), and cutaneous (19%) localizations were also observed.
      The mean delay to diagnosis was 40 months, more than 1 year in 7 patients. A
      definitive diagnosis could not be made for 5 patients because of lack of
      histological evidence, but clinical and biological arguments suggested diagnosis
      of WG. Antineutrophil cytoplasmic antibodies (ANCA) were assessed in 13 patients
      and were positive in all. The role of ENT biopsies was significant to our study
      (31%). The ENT specialist can play a very important role in the diagnosis of
      Wegener's granulomatosis.

PMID- 11845040
TI  - [Prognostic factors in epidermoid carcinoma of the mobile tongue classified as T1
      T2].
AB  - INTRODUCTION: Our aim was to evaluate the results and the prognosis of squamous
      cell carcinoma of the mobile part of the tongue stage T1-T2 treated by surgery
      and radiotherapy at the Institute Jules Bordet from January 1950 to 31th December
      1993. METHODS: According to the classification TNM (UICC 1978) 165 consecutive
      patients classified as follow: 73 T1No (stage I), 64 T2No (stage II), 7 T1N1 and
      20 T2N1 (stage III) and 1 patient T2N2 (stage IV). All patients underwent surgery
      beforehand. 136 patients received additional brachytherapy. RESULTS: In this
      study were included 117 men and 48 women with an average age of 60 years. The
      rate of relapse on the primary tumoral site amounted to 16,4% and the residual
      relapse to 40%. The survival note without relapse was evaluated respectively at 3
      years in 67% of the tumours T1 (against 28% for the T2), at 5 years for 59% for
      tumours T1 (against 26% for T2). From the clinical point of view the survival
      rate without relapse was of 5 years for 61% of stage I, 29% of stage II and 24%
      of stage III. A more extensive investigation shows the statistic influence, such
      as age (p<0.004), size of the tumour (p<0.007) and its shape (p<0.0007) on the
      total survive rate. The state of the nodes (p<0.02) and the safety margins
      (p<0.04) are statistically less associated. The survival rate with no relapse
      according to a study considering statistical factors, is significantly influenced
      by the size (p<0.0002) and age (p<0.0003). CONCLUSION: T1-T2 stages of the mobile
      tongue are characterized by a limited local spread but a more regional spread and
      diversified therapeutic approach with prognostic factors influencing the survival
      rate without forgetting the part played by the TNM classification.

PMID- 11845041
TI  - [Intracranial complications of acute mastoiditis].
AB  - We report a case of extradural abscess after acute mastoiditis in an 8-years-old
      boy. The clinic diagnostic of an intracranial complication is difficult. The most
      common present symptoms are fever, otalgia and otorrhea but are not specific.
      Neurologic symptoms are suggestive signs of an intracranial complication. We
      believe that, in acute mastoiditis performance of a CT scan of the brain and
      temporal bones with intravenous contrast, contribues to the diagnostic of
      intracranial complication. The diagnostic of thrombosis sinus sigmoid is evoked
      with slight contrast enhanced sinus sigmoid and failure to opacify. The
      characterisation of an epidural empyema is a hypodense epidural collection in a
      contrast-enhanced CT scan. The most common isolated organism are Streptococcus
      Pneumoniae, Staphylococcus aureus and Pseudomonas aeuginosa. The therapeutic
      management includes combination of intraveinous antibiotics, mastoidectomy and
      surgery of the intracranial complication.

PMID- 11845042
TI  - [Giant pleomorphic adenoma of the parotid gland: a case report and review of the
      literature].
AB  - We report the case history of a 72-year-old patient who had a giant parotid
      adenoma that developed over 12 years. Worrisome clinical signs started to develop
      when the tumor had reached the size of 50 cm and a weight of 2.6 kg. Histology
      reported a benign tumor of the parotid gland. We discuss this case in relation to
      the to similar cases in the literature, highlighting clinical and histological
      difficulties encountered in patients with giant tumors of the parotid.

PMID- 11845043
TI  - [What can be expected from biological therapies for Crohn's disease?].

PMID- 11845044
TI  - [Infliximab therapy for Crohn's disease anoperineal lesions].
AB  - AIM OF THE STUDY: To retrospectively evaluate the efficacy, the duration of
      response, and the tolerance of Remicade in anoperineal Crohn's disease. METHODS:
      Fifty patients with severe symptomatic and refractory anoperineal Crohn's lesions
      (38 fistulae and 29 cavitating ulcers and superficial fissures) were treated with
      3 intravenous infusions of Remicade (5 mg/kg) at weeks 0, 2 and 6. Efficacy was
      assessed using Allan's functional score and proctologic examination at 8 weeks
      (W8) and 24 weeks (W24) after the first infusion. RESULTS: At W8, a response was
      noted for 71% (27/38) of fistulae and 79% (23/29) of ulcers and fissures. Healing
      rates were 39% and 49%, respectively. Efficacy of Remicade at W8 did not vary
      according to sex, number and type of fistulae and other treatments. At W24, 58%
      (15/26) of patients with fistulae and 63% (10/16) of patients with ulcers or
      fissures had a response. The response rate at W24 was higher in patients having
      anoperineal Crohn's lesions for less than one year: 77% vs 32% (P=0.004). Median
      Allan's score significantly decreased from 3.9 before treatment to 1.7 at W2
      (P<0.001), 1.3 at W6 and 0.8 at W8. Median duration of response was 9.5 months
      (range: 0.5-12.5) after last infusion and was not influenced by associated
      treatments including immunomodulators. The relapse rate at 1 year was 64% for the
      responders followed at least one year (n=21). Minor adverse events occurred
      during 12% of all infusions. Eight patients had an infection, including one
      pneumonia. Eight patients developed a perineal abscess 16 weeks (range: 4-32)
      after the first infusion. CONCLUSION: Remicade is rapidly effective and well
      tolerated in anoperineal Crohn's lesions, but the high relapse rate stresses the
      need for long term therapeutic strategies in these patients.

PMID- 11845045
TI  - [Palliative treatment of rectal carcinoma using a urologic resectoscope].
AB  - OBJECTIVE: The aim of this study was to report our experience with endoscopic
      transanal resection (ETAR) using a urologic resectoscope for palliative treatment
      of rectal carcinoma. METHODS: Outcome in patients who underwent ETAR with a
      urologic resectoscope between October 1992 and March 1999 are reported. RESULTS:
      The 60 ETAR procedures were performed in 37 patients (19 men and 18 women, median
      age 82 years). Morbidity was 10% (6 patients) and mortality was 2.7% (1 patient).
      Median hospital stay for the procedure was 5 days. Symptom control was achieved
      in 86% of the patients (40% partial control, 46% complete control). Colostomy was
      performed in 8 patients 7 months after ETAR. At study end, 4 patients were alive.
      Median survival was 14 months (range 0 - 62). The 1-, 2-, and 5-year survival
      rates were 54, 32 and 5%, respectively. CONCLUSION: ETAR is a simple, minimally
      invasive and economical method for palliative treatment of patients with rectal
      carcinoma. ETAR is a useful addition to the surgeon's armamentarium.

PMID- 11845046
TI  - [Unresected colorectal liver metastases: prognostic value of laboratory
      variables].
AB  - OBJECTIVE: To search for laboratory variables having independent prognostic
      signification in patients with unresected colorectal liver metastases. METHODS:
      We have systematically reviewed the biomedical literature using the methodology
      recommended by the Committee on Evidence-Based Laboratory Medicine of the
      International Federation of Clinical Chemistry and Laboratory Medicine, and
      taking into account the Consolidated Standards of Reporting Trials Statement.
      RESULTS: Of 644 publications retrieved, the application of strict exclusion and
      inclusion criteria allowed us to include only eight studies in our systematic
      review. The main laboratory variables evaluated in these eight studies were serum
      carcino-embryonic antigen, alkaline phosphatase, albumin, bilirubin, and plasma
      prothrombin time. None of these variables were unanimously found to have an
      independent prognostic significance. A meta-analysis was not possible, mainly
      because of heterogeneity within the primary studies and these contradictory
      results. CONCLUSIONS: Current evidence would not support the routine use of
      laboratory variables as independent prognostic variables in patients with
      unresected colorectal liver metastases. Taking into account the inadequate
      quality of the published studies, this negative conclusion might be provisory
      only. Until better designed studies are published, a number of arguments would
      support to recommend pre-treatment measurement of serum carcino-embryonic antigen
      and alkaline phosphatase in patients participating in clinical trials.

PMID- 11845047
TI  - [Rationale and prospects for the use of cyclooxygenase-2 (COX-2) inhibitors in
      colorectal cancer].

PMID- 11845049
TI  - [Synopsis: Pelvic rectal static disorders].

PMID- 11845050
TI  - [Comment on case report: A difficult mourning period].

PMID- 11845053
TI  - [A code of ethics for clinical research].

PMID- 11845054
TI  - [Chemotherapy and immunosuppression in patients with hepatitis B or C].

PMID- 11845055
TI  - [Natural history of focal nodular hyperplasia. A retrospective study of 44
      cases].
AB  - AIM: To evaluate the natural course of focal nodular hyperplasia according to
      hormonal status. METHODS: Forty-four patients were included in this retrospective
      study. Tumor size was assessed with ultrasound examination. We studied the
      influence of hormone status on the course of the disease. RESULTS: All patients
      were women, the median age at diagnosis was 35 years and the median follow-up was
      45 months. Ten patients were symptomatic at diagnosis, while none were
      symptomatic at the end of follow-up. The median size of the lesions was 56 mm. No
      complications occurred. The size of the tumor remained stable in 19 patients,
      increased in 12 and decreased in 13. Twenty-one of 37 patients stopped taking
      oral contraceptives at diagnosis: the lesion remained stable in 11 patients,
      increased in 3 and decreased in 7. Two patients didn't stop taking oral
      contraceptives: the lesion increased in one, decreased in the other. Six patients
      became pregnant and 6 patients went into menopause during follow-up: the lesion
      remained stable in 3 and 4 patients respectively. CONCLUSION: Focal nodular
      hyperplasia is a benign lesion. Tumor size remained stable in most cases. It
      seems that the hormonal status has little or no influence on the course of the
      disease.

PMID- 11845056
TI  - [Receptors for hepatitis C virus: update data].

PMID- 11845057
TI  - [Code of professional ethics in clinical research].

PMID- 11845058
TI  - [Collagenous gastritis, duodenitis, ileitis and colitis].

PMID- 11845059
TI  - [Lansoprazole-associated collagenous colitis].

PMID- 11845060
TI  - [Retrosacral hematoma of Morel-Lavallee: a rare cause of perianal sepsis].

PMID- 11845061
TI  - [Giant colonic diverticulum].

PMID- 11845062
TI  - [Interest of a combined modality treatment in unresectable gallbladder carcinoma.
      A case report].

PMID- 11845063
TI  - [Massive splenic infarction in a patient with alcoholic cirrhosis].

PMID- 11845064
TI  - [Hemolitic uremic syndrome with hypertransaminasemia following treatment by
      interferon for chronic myeloid leukemia].

PMID- 11845065
TI  - [Eradication of hepatitis C virus after 3 months of interferon and ribavirin
      treatment in an a interferon non-responder patient with chronic hepatitis C].

PMID- 11845066
TI  - [Decompensation of lower limb arteritis after bone and joint surgery].
AB  - PURPOSE OF THE STUDY: Decompensation of lower limb arteritis after bone and joint
      surgery is an unusual finding compared with the large number of procedures
      performed in both emergency and controlled settings. There is however a
      functional and limb-threatening risk that must not be overlooked. MATERIAL AND
      METHODS: We report a series of 9 patients followed in our department over the
      last 3 years. Emergency surgery had been required in 6 patients after trauma and
      3 had undergone a planned orthopedic procedure. All the patients had at least one
      vascular risk factor, and 7 of them had a cardiovascular history. The inaugural
      sign was a trophic disorder due to a grade IV decompensated arteritis in 8
      patients, including 2 with nonunion. Delay to treatment ranged from 1 to 3
      months. Acute embolic ischemia required emergency care in 1 patient. RESULTS: A
      revascularization procedure was performed on 6 limbs and was successful in 3.
      There were also 6 amputations, three initially, 1 after septic shock and 2
      because revascularization was impossible. Three of the amputations were required
      after failed revascularization. Prosthesis wearing and walking was possible in
      only two amputated patients. Overall rate of successful salvage was 33% (3
      successful revascularizations among 9 limbs). One of the nonunions healed after
      revascularization; the limb was amputated for the other one. One patient died
      from septicemia. DISCUSSION: Our series further illustrates the severity of
      decompensated arteritis after bone and joint surgery, emphasizing the importance
      of searching for cardiovascular risk factors and functional signs suggestive of a
      vascular disorder. Arterial duplex Doppler and if necessary arteriography of the
      lower limbs should be obtained in case of doubt. Two different situations can be
      distinguished depending on the predictable vascular risk and the localization of
      the planned bone reconstruction. If the patient has an asymptomatic proximal
      arteritis and bone and joint surgery is planned above the knee, a
      revascularization procedure would not appear necessary prior to bone surgery. In
      other cases, it may be more advisable to treat the arteritis before attempting
      bone surgery. For trauma victims, the osteosynthesis technique depends greatly on
      knowledge of the vascular risk.

PMID- 11845067
TI  - [Computer-assisted implantation of a total knee arthroplasty: a case-controlled
      study in comparison with classical instrumentation].
AB  - PURPOSE OF THE STUDY: The quality of total knee arthroplasty (TKA) implantation
      is an essential factor determining long-term outcome. Computer-assisted
      implantation could improve quality compared with conventional manual
      instrumentation. MATERIAL AND METHODS: We studied the radiographic quality of TKA
      implantation in 100 patients with primary degenerative knee disease who underwent
      a computer-assisted procedure guided by an informatic navigation system without
      imagery (group A) or a conventional manual procedure (group B). The two groups
      were matched for age, sex, initial frontal mechanical tibiofemoral angle and
      severity of the degenerative lesions. Postoperative telemetry was used in
      accordance with the Knee Society guidelines to measure the frontal mechanical
      tibiofemoral angle and the frontal and sagittal tilt of the tibial and femoral
      components. The number of optimal implantations for the five measured criteria
      was chosen as the main study criterion. The two groups were compared using the
      chi-squared test with statistical significance set at 5% and power at 80%.
      RESULTS: Globally, implantation of the prosthesis was considered to be optimal in
      33 patients in group A and in 15 in group B (p<0.001). Mean angles were not
      different between the two groups, except for sagittal tilt of the femoral piece.
      The frontal mechanical tibiofemoral angle was considered optimal in 47 patients
      in group A and in 39 in group B (p<0.05). A significant improvement in the
      quality of the implantation was also found in group A for frontal tilt of the
      femoral piece (p=0.05), frontal tilt of the tibial piece (p<0.05) and sagittal
      tilt of the tibial piece (p<0.001). No particular peroperative difficulty or
      complication was related to the navigation system. DISCUSSION AND CONCLUSION: The
      navigation system allowed a significant improvement in the quality of
      implantation of TKA compared with conventional instrumentation controlled by the
      surgeon's hand and eye. Only minimal changes in the operative technique are
      necessary and standard preoperative investigations remain unchanged. Long-term
      survival of prostheses implanted with this system could thus be improved compared
      with manually implanted TKA. The system used here does not involve preoperative
      imaging and allows a precision to the order of 1 degree for angles and 1 mm for
      lengths.

PMID- 11845068
TI  - [Arthroscopy-assisted revision in failed reconstruction of anterior cruciate
      ligament: 32 cases].
AB  - PURPOSE OF THE STUDY: The aim of this retrospective study was to analyze mid-term
      outcome after anterior cruciate ligament (ACL) revision performed
      arthroscopically with a patellar tendon graft. MATERIAL AND METHOD: The series
      included 32 revision arthroscopies for ligamentoplasties of the ACL performed
      after primary intraarticular plasty. Outcome was assessed using the IKDC score at
      least 2 years after revision surgery. A free patellar autograft was used in all
      cases in association with an anterolateral plasty in 9 cases using the Marshal
      MacIntosh technique. There were 25 men, mean age 28.5 years. Mean follow-up was 4
      years. The initial plasty was done with a synthetic ligament in 15 cases and an
      autograft in 17, including 12 patellar tendons. In 3 cases, the revision was
      needed for synovitis involving the synthetic ligament. In all the other cases,
      revision was indicated for instability, most of the failures resulting from a
      defective femoral position (particularly for autografts) or renewed trauma.
      RESULTS: Among the 23 patients who were initially competition-level athletes, 18
      recovered their sports activity, 8 at an equivalent level. At last follow-up, the
      IKDC global scores were: A 5 patients (15.6%), B 16 patients (50%), C 8 patients
      (25%), D 3 patients (9.4%). Certain residual laxity was present in 3 cases (C and
      D laxity score for 2 of them). A tibiofemoral narrowing was present in the medial
      compartment in one patient alone. Factors of poor prognosis for the IKDC score
      were: long delay from accident to initial treatment (p=0.04), associated medial
      meniscectomy (p=0.02). Presence of an initial femoral tunnel had no effect on
      revision due to its very anterior situation. DISCUSSION: The technical difficulty
      of revision of an intra-articular ligamentoplasty of the ACL is to position the
      new transplant so it will satisfy the same requirements as the initial plasty.
      This position depends particularly on the femoral component due to the importance
      of the position of the initial femoral tunnel and the degree of bone loss
      (osetolysis, ablation of an interfering screw.). The homolateral patellar tendon
      was used for the graft in all cases except one and iterative use of the patellar
      tendon for grafting did not cause supplementary morbidity. The patellar tendon
      remains the transplant of choice for ligament reconstruction. Meniscectomy had a
      deleterious effect on the final outcome. As for first intention plasty, the
      therapeutic strategy should preserve as much meniscal stock as possible,
      depending on the type and degree of damage. CONCLUSION: Revision ACL plasty can
      provide good anatomic results although functional outcome is less satisfactory
      than after primary intention ligamentoplasty. A precise clinical and radiographic
      analysis of the cause of failure of the primary plasty must be obtained in order
      to establish a surgical strategy allowing the most clinically effective plasty
      with well positioned bone tunnels.

PMID- 11845069
TI  - [Outcome of 95 stable meniscal tears left in place after reconstruction of the
      anterior cruciate ligament].
AB  - PURPOSE OF THE STUDY: The purpose of this retrospective analysis was to study
      clinical and radiological outcome of 95 stable meniscal tears left in place after
      arthroscopic reconstruction of the anterior cruciate ligament with a free
      patellar autograft (with or without a lateral component). MATERIAL AND METHODS:
      We reviewed 86 patients who had undergone arthroscopic treatment for chronic
      anterior laxity (56% solely anterior laxity) with at least one meniscal lesion
      left in place after ligamentoplasty. IKDC criteria and ARPEGE scores were
      recorded. A total of 95 stable meniscal lesions had been left in place: 35
      lateral lesions (80% longitudinal tears and 77% posterior lesions) and 60 medial
      lesions (55% peripheral disinsertions and 90% posterior lesions). The lesions
      measured a mean 10 mm (range 5-20 mm) for the lateral and medial menisci. Mean
      follow-up was 4 years (range 3-9 years). These patients were young (mean age 26
      years), and predominantly men (75%). The right knee was involved in 53% of the
      cases. RESULTS: At last follow-up, 26% of the patients were grade A, 65% B, 7% C
      and 2% D according to the IKDC criteria. No revision procedure was required for
      lateral menisci despite the large size of the lesions left in place in certain
      cases. Among the 60 medial lesions left in place, 10 (17%) had become symptomatic
      (8 bucket-handle, 1 longitudinal tear, 1 posterior fragment) and required surgery
      a mean 3 years (range 1-6 years) after ligamentoplasty. There was no statistical
      difference between functional score, residual laxity, or type of stabilization in
      patients who had revision surgery for symptomatic meniscal lesions and the
      others. Inversely, these lesions were statistically larger (p=0.038) than the
      others (mean 13 mm versus 9.8 mm). CONCLUSION: Outcome of stable meniscal lesions
      left in place after treatment for anterior laxity depends on the meniscus
      involved. For the lateral meniscus, irrespective of the size of the lesion,
      therapeutic abstention has no clinical impact at 4 years. Inversely, for the
      medial meniscus, 37.5% of the lesions measuring more than 10 mm that were left in
      place required revision while only 9% of those measuring less than 10 mm
      necessitated subsequent surgery. Beyond 10 mm, therapeutic abstention led to a
      revision procedure in 17% of the cases, suggesting the usefulness of a discussion
      on other indications. Stable lesions of the medial meniscus should not be left in
      place if they measure more than 10 mm.

PMID- 11845070
TI  - [Strain gauge measurements on a one-side external fixation: a prospective series
      of 11 tibial shaft fractures].
AB  - PURPOSE OF THE STUDY: External fixation is often the treatment of choice for open
      complex fractures of the tibia. For closed tibial shaft fractures, it is
      generally a second choice alternative. The purpose of this study was to determine
      whether fusion of closed and open fractures of the tibia can be successfully
      achieved with a one-side external fixator equipped with strain gauges and to
      evaluate complications of this type of treatment. MATERIAL AND METHODS: A
      consecutive series of 11 mid shaft fractures of the tibia (4 closed fractures and
      7 Gustilo grade I and II open fractures) in 11 patients (mean age 29 years) were
      treated with a one-side external fixator. Strain was measured weekly to adjust
      the treatment. A Sarmiento walking cast was applied in all cases 4 weeks after
      removal of the external fixator. RESULTS: All 11 fractures healed without
      complications and without pin tract infection. Mean delay to consolidation was
      20.5 weeks (range 13 - 29.5 weeks). One patient required a revision procedure for
      decortication and bone graft at 12 weeks. Weight bearing (50% of body weight on
      the injured limb) was achieved at 6.7 weeks (mean) and total weight bearing at
      11.9 weeks. The external fixator's strain curves were compatible with normal
      healing in 3 cases, with slow healing in 3 and with retarded healing in 3 others.
      Two of the curves did not show recognizable patterns despite a favorable clinical
      and radiological course to healing. DISCUSSION: Early detection of a pathological
      pattern of fracture healing followed with a strain gauge enabled adaptation of
      treatment in all cases. Decortication with bone grafting was necessary in one
      patient. In two other cases, compression of the fracture with the external
      fixator or dynamic locking were sufficient to achieve a favorable healing
      pattern. This small series demonstrated that bone healing can be achieved within
      usual delays with external fixation and without major complications. Use of
      strain gauges on the external fixator allowed early detection of retarded healing
      and subsequent modification of the treatment protocol. This type of treatment
      might be an interesting therapeutic alternative for the treatment of closed
      fractures of the tibial shaft.

PMID- 11845071
TI  - [Tibio-talar arthrodesis: long term influence on the foot].
AB  - PURPOSE OF THE STUDY: The aim of this study was to evaluate the long-term effect
      of tibiotalar arthrodesis on function, clinical and radiological tolerance, and
      subtalar joints. MATERIAL AND METHODS: We reviewed 37 cases of tibiotalar
      arthrodesis in 27 young patients who were generally manual workers. Their mean
      age at surgery was 46 years and mean follow-up at review was 12.8 years (range 5
      26 years). Functional outcome was assessed with the Duquennoy scale. We reviewed
      the anterioposterior and lateral weight-bearing views as well as the lateral view
      in dorsal and forced plantar flexion. RESULTS: Mean functional outcome was good
      and very good in 66% of the cases, fair in 30% and poor in one case. Total pain
      relief had been achieved in 45% of the cases with a mean walking distance of 1500
      m without crutches. Residual mobility at last follow-up was 13 degrees for the
      mediotarsal joint. This mobility allowed the arthrodesed foot to adapt to gait.
      Radiologically, fusion had been achieved in 83% of the cases within 3 months. The
      overall functional score fell off proportionally with the degree of arthrodesis
      valgus starting at 5 degrees. Likewise pes equinus > 10 degrees led to pain and
      reduced motion. The subtalar joints were affected in all cases, leading to poor
      adaptation of the foot on uneven ground. Grade 1 osteoarthritis affected the
      mediotarsal joint and was more marked in case of equine fixation. DISCUSSION: Our
      results are similar to those reported in the literature. We had 4 cases of
      nonunion in patients with risk factors previously discussed in the literature.
      CONCLUSION: Arthrodesis remains a useful method for treating talocrural
      osteoarthritis, providing good long-term results. The position of the fixation
      should be 90 degrees in the sagittal plane and 0 degrees to 5 degrees valgus in
      the frontal plane.

PMID- 11845072
TI  - [Tridimensional gait analysis after unilateral subtalar arthrodesis].
AB  - PURPOSE OF THE STUDY: Subtalar arthrodesis can be useful in various conditions.
      Initially used for the treatment of congenital or acquired foot deformities, it
      was later applied to surgical repair of traumatic injury. The subtalar joint does
      however play an important role in gait, particularly for transmitting rotational
      movement of the leg to the foot. The functional outcome after subtalar
      arthrodesis has been the object of many studies. These studies examined clinical
      and radiological results and raised the problem of determining the appropriate
      extent of the fusion. None of these studies has however provided a three
      dimensional analysis of gait after subtalar arthrodesis, performed in the present
      work. MATERIAL AND METHODS: We used the Vicon VX3D system with 2 integrated force
      platforms. Acquisition was made at 50 Hz. The Vicon recording was coupled with
      EMG recordings of the gastrocnemius, the rectus, the anterior tibialis, and the
      glutius medius. Gait was analyzed in 8 patients who had undergone unilateral
      subtalar arthrodesis at least 18 months earlier. Several recordings were made for
      each patient but only one complete gait cycle was retained for analysis of
      kinematic, kinetic and electromyographic curves and ground reaction forces.
      Wilcoxon's test for paired series was used to compare the operated side to the
      healthy side (excepting EMG recordings). RESULTS: The operated and healthy side
      were significantly different. Total amplitude of joint movement was lower for the
      operated side: 16.5 degrees versus 21.5 degrees for the healthy side. Peak power
      generated at the ankle for plantar flexion was lower at the end of the stance
      phase. Electromyography recordings showed a shift in muscle activity between the
      healthy and fused foot. DISCUSSION: Few statistical differences were found
      between the tested values. It can thus be concluded that gait pattern is globally
      symmetrical after subtalar arthrodesis and that this fusion has little functional
      impact on the knee or the hip. The difference in amplitude between the healthy
      and operated side showed a wider variability than observed by Winter in the
      healthy subject that was also greater than the measurement error reported by
      Laasel. We did not perform a statistical analysis of the EMG data since the
      values recorded were arbitrary and the observed shift in activities had no
      general impact. CONCLUSION: Despite the reduction in flexion-extension amplitude
      of the ankle, subtalar arthrodesis allows a globally symmetrical gait in the
      experimental conditions described.

PMID- 11845073
TI  - [Dynamic pedobarography in postoperative evaluation of pes cavovarus].
AB  - PURPOSE OF THE STUDY: Pes cavovarus is a complex deformity of the forefoot, the
      midfoot and the hindfoot, frequently of neuropathologic etiology. The goals of
      surgical interventions consist of anatomical and functional correction of the
      foot deformity by soft tissue and bony procedures. Preoperative planning and
      postoperative assessment are based on clinical and radiographic examination. The
      present study was undertaken to find out if pedobarographic outcomes correlate
      with those postoperative results and if the dynamic pedobarography provides
      useful information in the functional evaluation of cavovarus feet. MATERIAL AND
      METHODS: Sixteen patients with cavovarus foot deformity (mean age 32.8 years,
      range 17-56) with a total of 21 feet were examined before and after surgery. The
      average follow-up time was 24 months (range 6-50). The study protocol included
      physical examination, angle measurements on weightbearing radiographs and dynamic
      pedobarography. The patients performed five trials at self-selected speed for
      each foot. The amount of correlation was established between: plantar peak
      pressure pattern and patient's subjective functional result, the evidence of
      callosities and increased peak pressures in forefoot and midfoot regions of
      interest, the change of calcaneal pitch or Hibbs' angle (first metatarsal -
      calcaneal axis) and the midfoot contact area. RESULTS: The patient's functional
      opinion and pedobarographic improvement of peak pressures correlated in 7 feet,
      the patients estimated the result better in 13 feet and worse in 1 foot. In 4
      regions of interest callosities and increased peak pressures occurred together in
      69% of the cases, in 15.5% callosities were observed without augmented peak
      pressures and in 15.5% increased peak pressures were measured without evidence of
      callosities. No correlation was found between radiographic and pedobarographic
      parameters which describe a reduction of the cavus deformity: calcaneal pitch
      angle and midfoot contact area (Pearson correlation coefficient r=- 0.36), Hibbs'
      angle and midfoot contact area (r=0.55), although all parameters changed
      significantly (p=0.001). DISCUSSION AND CONCLUSION: Pre- and postoperative
      assessment of the cavovarus foot is mainly based on static methods such as
      clinical and radiographic evaluation. The results of this study demonstrate that
      the dynamic measurement of plantar peak pressures and contact area offers limited
      information about functional and anatomical improvement after surgery. Patients
      with severe deformities and muscular discoordination have difficulties walking
      consistently on the platform at each trial and severe decrease of plantar contact
      area makes the exact positioning of the masks difficult, which leads to problems
      with standardised measurements. In this context, the dynamic pedobarography
      cannot be used as a profitable diagnostic tool which provides an objective
      measurement that can add a dynamic component to a clinical or radiographic
      examination.

PMID- 11845074
TI  - [Scarf osteotomy of hallux valgus in children and adolescents].
AB  - PURPOSE OF THE STUDY: The aim of this study was to analyze the results of
      surgical treatment of hallux valgus using scarf osteotomy in children and
      adolescents. MATERIAL AND METHOD: Twelve children and adolescents (19 feet)
      operated on with scarf osteotomy were reviewed retrospectively with a mean follow
      up of 15 months. Clinical and radiographic results were assessed. RESULTS: We
      obtained 10 good results (asymptomatic cases), 9 poor with residual symptoms such
      as pain or cosmetic problems. Two populations could be identified considering the
      metatarsus varus and distal metatarsal angle. Those with metatarsus varus >/= 10
      degrees or normal distal metatarsal angle had good results. Those without
      metatarsus varus had poor results. There was no disturbance of growth.
      DISCUSSION: Scarf osteotomy can be used in children without risk of hindering
      growth. Nevertheless, good results can be achieved only in cases of true
      metatarsus varus and normal distal metatarsal angle. In other cases, a different
      osteotomy of the first metatarsal would be preferable.

PMID- 11845075
TI  - [Double measurement of the Bohler angle: prognostic value of radiological angles
      in posterior facet fractures of the calcaneus].
AB  - In 1931, Bohler proposed that measuring the radiological angle of the tuberosity
      could be useful in posterior facet fractures of the calcaneus to evaluate initial
      damage as well as reduction quality. In opposition to the 1998 SOFCOT symposium,
      certain authors considered that the Bohler angle has no prognostic value.
      Progress in pathological anatomy has helped to better understand posterior facet
      fractures, justifying the use of a "double measurement". The fundamental fracture
      line separates the posterior facet into a lowered medial fragment and a pivoted
      lateral fragment. The double contour of the posterior facet visualized
      radiographically allows measurement of a medial Bohler angle and a lateral Bohler
      angle. It is demonstrated that is the smaller the medial Bohler angle, the
      greater the subtalar degeneration. Surgical restoration of a satisfactory Bohler
      angle is a necessary prerequisite for a good outcome. "Double measurement" of the
      Bohler angle on the lateral view contributes to the prognostic value of this
      historical angle.

PMID- 11845076
TI  - [Recurrent aggressive chondroblastoma: two cases and a review of the literature].
AB  - Chondroblastoma is a rare benign bone tumor. Treatment currently consists of
      curettage and bone graft. Prognosis depends basically on a relatively high rate
      of recurrence, between 5 and 38%, sometimes with local seeding of soft tissues
      and joint space. Such recurrences require wide resection with arthrodesis or even
      amputation. A 13-year-old girl with a humeral head chondroblastoma as treated by
      curettage and iliac bone graft. Six months later, a recurrence occurred with
      extension into the rotator cuff and the metaphysis. Remission was achieved by
      extensive surgical resection and hemiarthroplasty. The second case was a 14-year
      old boy with a chondroblastoma of the right talus. He was treated by curettage
      and packing with bone substitute. After 2 recurrences with soft tissue and intra
      articular extension, we performed a wide resection with reconstruction using a
      vascularized fibular graft. Many other cases in the literature illustrate such
      complications. We tried to find factors predictive of recurrence. Recurrence is
      observed when curettage was incomplete or when tumor cells were disseminated
      during surgery. Chondroblastoma is a benign bone tumor, but prognosis depends on
      the rapidity and severity of recurrence. Curettage should be as complete as
      possible and care should be taken to avoid contaminating the operative field.

PMID- 11845077
TI  - [Total bilateral carpal coalition with carpometacarpal fusion: one case].
AB  - Carpal coalition may involve more than two carpal bones which is more common when
      coalition occurs as part of a syndrome of congenital malformations. We describe
      an unusual case of congenital complete entire carpal coalition with massive
      carpometacarpal coalition except the first carpometacarpal joint and abnormal
      distal radioulnar joint bilaterally. In addition, radiocarpal joint surfaces were
      slightly irregular but compatible. There were abnormal distal radioulnar joints
      and ulnar styloids articulated with the ulnar side of the lunate of the both
      wrists.

PMID- 11845078
TI  - [Intramedullary interlocking nailing for humeral fractures: report of 38 cases
      treated by Russel and Taylor nail].
AB  - PURPOSE OF THE STUDY: We assessed outcome after intramedullary interlocking
      nailing for humeral fractures to identify problems and indications in comparison
      with reports in the literature. MATERIAL AND METHODS: We implanted the Russel and
      Taylor nail to treat 38 fresh humeral shaft non-pathological fractures using 33
      anterograde insertions and 5 retrograde insertions. RESULTS: All patients were
      examined at a mean follow-up of 16.3 months. Problems and complications involved
      3 open procedure conversion, 3 peroperative re-fractures, 2 locking errors, 2
      secondary dismantelings, 2 regressive iatrogenic palsies, and 4 cases of pain due
      to protruding material. First intention bone healing was achieved in 34 cases and
      following a revision procedure in 2. Two cases of nonunion were not reoperated.
      The Neer and Constant scores, used to assess functional outcome, identified 5 non
      satisfactory results. DISCUSSION: The risk of infection with locking nails is
      low, as is the risk of nervous complications which are generally related to
      traction manoeuvres during reduction. Bone healing is easily achieved if the
      assembly is perfectly stable. The risk of disassembly or nonunion is related to
      technical errors: defective locking, insufficient hold in the bone fragments. The
      risk of stiffness or rotator cuff tears is low, generally related to protrusion
      of the material and not to insertion through the cuff muscles. Retrograde
      insertion can be recommended for fractures of the distal third of the humeral
      shaft. CONCLUSION: Insertion of the Russel and Taylor intramedullary locking nail
      requires a learning curve to minimize the risk of iatrogenic complications. It
      can be proposed for fractures of the mid-third of the humeral shaft and can be
      discussed for the proximal and distal thirds if perfect stability can be obtained
      on the short bony fragment.

PMID- 11845079
TI  - [Treatment of humeral shaft fractures with the Marchetti nail: 50 cases].
AB  - PURPOSE OF THE STUDY: There is no universal agreement concerning the most
      appropriate method for treating humeral shaft fractures. Orthopedic treatment was
      long proposed due to the risks of surgical management. Screwed plate fixation
      raises the risk of infection, neurological injury and nonunion. Anterograde
      nailing can lead to subacromial conflicts. The purpose of this study was to
      analyze results of an elastic retrograde nailing technique using the Marchetti
      nail. This method would appear to offer the advantages of closed osteosynthesis
      without interrupting the rotator cuff. MATERIAL AND METHODS: Fifty fresh
      traumatic fractures of the humerus were treated with Marchetti nailing between
      December 1995 and June 1999. Ten patients had died at last follow-up after having
      achieved bone healing. Outcome was assessed at a mean 22 months post-surgery for
      39 patients. The AO classification and the Hackethal classification modified by
      De la Caffiniere were used. Outcome was assessed according to the Stewart and
      Hundley classification. RESULTS: Very good outcome was achieved in 13 patients
      (33%), good outcome in 21 (54%) and poor outcome in 5 (13%). The assembly
      dismounted in 1 patient who required revision for pin insertion. Two cases of
      nonunion and two cases with poor function were observed. Mean delay to union was
      10 weeks. There were no cases of infection or iatrogenic radial nerve palsy.
      Secondary fracture at material ablation occurred in 2 cases. DISCUSSION AND
      CONCLUSION: Closed fixation is an advantage of this method (minimal risk of
      infection and radial injury). In addition, the rotator cuff is not perturbed. The
      drawbacks include the risk of secondary fracture, almost exclusively at ablation.

PMID- 11845080
TI  - [Complex fractures of the proximal end of the radius and ulna in adults: a new
      classification].
AB  - Unlike injuries involving only one of the forearm bones, complex lesions of the
      proximal end of the radius and the ulna are particularly unstable. Various
      situations-Monteggia fracture, transolecraneal dislocation, or fracture
      dislocation-are encountered. The classification systems proposed to date and
      recalled here are insufficient, making it difficult to provide optimal therapy
      and also hindering comparison between published series. We propose a descriptive
      classification including all the anatomic varieties of complex fractures of the
      proximal end of the radius and the ulna. This classification is based on our
      experience with 38 cases and takes into account 4 basic elements: the height of
      the ulnar fracture line, the direction of the displacement of the proximal
      radius, the association of a fracture of the proximal radius and/or of the
      coronoid process.

PMID- 11845081
TI  - [Complex fractures of the proximal end of the radius and ulna in adults: a
      retrospective study of 38 cases].
AB  - PURPOSE OF THE STUDY: Complex lesions of the proximal end of the radius and ulna
      are uncommon and generally associate a fracture of the proximal ulna and a
      dislocation of the radial head, which also may be fractured. We assessed the
      effect of the type of fracture and treatment on functional outcome and
      complications. MATERIAL AND METHODS: Thirty-eight adults (25 men and 13 women)
      were treated for complex fractures of the proximal end of the radius and ulna.
      For 25 of them, mean follow-up was 2.4 years. For the ulna, there was an
      epiphyseal fracture in 10 cases, a metaphyseal-epiphyseal fracture in 16 and a
      diaphyseal fracture in 12. The coronoid process was fractured in 20 cases and the
      proximal radius in 19. There was an anterior displacement in 24 cases. There were
      9 open fractures and 13 patients had another injury of the upper limb. Functional
      outcome was assessed with a 100 point scale using subjective (pain) and objective
      (active motion, muscle force, stability) criteria. RESULTS: For the 25 fractures
      with more than 1 year follow-up, outcome was very good in 8, good in 6, fair in 8
      and poor in 3. The pain and muscle force scores followed a similar pattern.
      Motion appeared as the determining factor for good outcome. Seven early revisions
      (2 for deep infections, 2 for disassembly of the fixation system, 3 for
      insufficient fixation) were required among the 38 patients. Among the late
      complications, there were 3 nonunions, 5 misalignments, and 4 proximal radio
      ulnar synostoses. Six elbows required revision to restore motion. DISCUSSION:
      Certain characteristics of the fractures were predictive of poor outcome: skin
      opening, association with a lesion of the homolateral upper limb, mirror lesion
      of the lateral condyle, metaphyseal-epiphyseal fractures, communitive fractures,
      presence of a fracture of the radial head or the coronoid process. CONCLUSION:
      Complex proximal fractures of both bones of the forearm threaten the functional
      prognosis of the upper limb due to the risk of stiffness. Successful treatment
      depends on three factors: stable anatomic reconstruction of the ulnar
      articulation, and reconstruction of the lateral column and the coronoid process,
      necessary for a stable elbow. In addition, early mobilization, possible with a
      stable osteosynthesis, is indispensable for recovering useful joint movement.

PMID- 11845083
TI  - [Experimental study of compression by Herbert screw in carpal scaphoid fracture].
AB  - PURPOSE OF THE STUDY: The purpose of this experimental work was to obtain a
      radiographical assessment of the effect of the compression achieved with the
      Herbert screw due to its different thread diameters by comparing the real and
      expected reduction of interfragment gap (IFG) on cadaver bones. To better
      understand and define the limits of this "self-compressing" effect and to study
      the usefulness of screw sizes smaller than the scaphoid, we measured the maximal
      and mean reduction of IFG without using the instrumentation. MATERIAL AND
      METHODS: Twelve scaphoids were obtained from fresh cadavers. The scaphoid holes
      were drilled and tapped in the largest axis of the scaphoid, in a central
      position parallel to an anti-rotation wire. A transverse osteotomy was made in
      the mid third of the scaphoid to simulate a Schernberg grade III fracture. The
      real IFG reduction was defined as the difference between the gap measured before
      and after screwing. The expected IFG reduction was defined by multiplying the
      number of screw turns by the pitch height per turn. RESULTS: On the reduction
      average, a Herbert screw produced a 1.1 mm IFG reduction. The maximal reduction
      IFG measured was 1.5 mm. For 7 cases, the real IFG reduction was larger than
      expected, for 4 cases it was smaller than expected and for 1 case the difference
      was considered negligible. The Fisher test did not demonstrate any significant
      statistical difference between the real and expected IFG reduction for all
      scaphoids. The operator perceived a subjective sensation of compression after one
      screw turn that continued up through the last turn. DISCUSSION: The Herbert screw
      develops maximal compression force when all the screw threads are totally
      anchored in the bone. The interfragment gap closes linearly, bringing the two
      bone fragments together. However, failure can result if the gap is too wide (>2
      mm), the screw is poorly positioned, or there is an inappropriate correspondence
      between screw length and diameter and scaphoid size. Unlike spongy bone screws,
      the Herbert screw has a round non-conical tip thread and a shallow thread that do
      not bring the bone fragments together. The perception of compression corresponds
      to the passage of the screw through the spongy bone and not to real narrowing of
      the gap between the fragments. In clinical practice, because of the use of
      instrumentation for open surgery in carpal scaphoid fracture, it is not necessary
      to rely on these data, but they can be useful for percutaneous screw insertion
      without a guidewire and without prior compression or for another localization.
      Peroperative radiographs should be obtained to assess the quality of the screw
      position and check reduction and the reality of the compression.

PMID- 11845082
TI  - [Progressive forearm lengthening in children: 14 cases].
AB  - PURPOSE OF THE STUDY: There are few indications for forearm lengthening in
      children. Several techniques have been proposed. We report our experience with
      progressive lengthening of the forearm in children using a unilateral axial
      external fixator and an improved technique consisting in initial insertion of an
      intramedullary guide wire. MATERIAL AND METHODS: Since 1990, we performed 14
      forearm lengthenings in 9 children. Radial agenesia (5 forearms in 4 children),
      and hereditary multiple exostosis (3 forearms in 2 children) were the predominant
      causes. The ulna was involved in 9 cases and the radius in 5. Age at initiation
      of the lengthening procedure ranged from 4.5 to 14.8 years (mean 9.9). The
      lengthening technique consisted in a transverse subperiosteal osteotomy of the
      bone shaft then progressive distraction with a unilateral axial external fixator.
      When axial deviation had to be corrected, we used a subtraction osteotomy. In our
      last 10 cases, we inserted an intramedullary guide wire in the lengthened bone.
      The external fixation was left in place throughout the lengthening procedure and
      until complete bone healing. Serial radiographs were used to assess bone healing,
      the degree of lengthening achieved and any axial deviation at the end of
      lengthening. RESULTS: All 14 forearms were reviewed at a mean 50.6 months. Mean
      lengthening was 26.4 mm (range 10 - 52 mm). There were no nerve or vessel
      complications. In one case, reducible claw finger completely regressed after
      temporary interruption of the lengthening. There were 6 cases of late healing
      requiring a secondary bone graft. The healing index was 61.9 days per cm gained
      length. There were 3 cases with an axial deviation at the end of lengthening.
      DISCUSSION: Insertion of a guide wire in the bone being lengthened reduced the
      risk of late healing compared with lengthening procedures without a guide wire,
      avoiding axial deviation. In addition, this technique led to more rapid bone
      healing so the fixator could be removed earlier. We have found this method to be
      easier to perform on a normally axed segment. This would require an initial
      subtraction osteotomy for prior alignment. CONCLUSION: Forearm lengthening is a
      difficult procedure. Use of an intramedullary guide wire associated with an
      external fixation and an initial osteotomy for axial correction when needed and
      possibly stabilization of the wrist is an important contribution, particularly
      for malformed forearms.

PMID- 11845084
TI  - [Straight femoral taper in cementless primary total hip replacement in less than
      65 year-old patients: multicenter study of 115 consecutive implantations at mean
      8,2 year follow-up].
AB  - PURPOSE OF THE STUDY: The Swedish Arthroplasty Registry experience with cemented
      primary total hip arthroplasty (THA) has pointed out age below 65 and high
      activity level as 2 major factors impairing THA long-term outcome. The aim of
      this study was to provide intermediate results of cementless femoral replacement
      in primary THA with use of the Alloclassic-SL grit-blasted titanium stem in "high
      risk" groups of patients. MATERIAL AND METHODS: From June, 1988 to June, 1992,
      127 cementless primary THA's were consecutively performed in<65 year old patients
      in 2 institutions. Acetabular components were all cementless (threaded cup in
      74%) and bearing surfaces were all alumina-ceramic 28mm heads on polyethylene
      (PE). Five patients (6 hips) died and 6 other hips were lost to follow-up before
      the 5-year minimum follow-up. Thus, 115 hips in 106 patients could be fully
      reviewed after a 8.2 year average follow-up period (range, 5 to 12 years). Mean
      age at surgery of the 62 male and 44 female patients was 52 years (range, 27 to
      65 years). RESULTS: Of the index group (127 hips), intra-operative fracture of
      the greater trochanter and early dislocation were noted in 4.7% and 3.2% of hips,
      respectively. Of the study group (115 hips), clinical results according to the
      Merle d'Aubigne and Charnley rating system were graded excellent and good in 94%
      of hips and fair in 6% (7 hips), with no poor result. Radiologically, early
      subsidence of more than 2mm could be detected in 8 hips (7%). Calcar atrophy and
      spot welds were noted in 81% and 89% of hips, respectively. Proximal reactive and
      lucent lines and mild proximal stress shielding were observed in 10.5% and 4.3%
      of hips, respectively. Ten-year survivorship with stem revision for any reason as
      the end point was 99.2% (92.4-99.9) (1 stem exchanged and reoriented for
      immediate dislocation). One revision is pending for extensive femoral osteolysis
      due to polyethylene (PE) wear. There was no stem fracture and no ceramic head
      breakage thus far. Overall PE-wear rate ranging 1-2 mm was detected in 13 hips
      (9.6%) and femoral osteolysis in 4 hips (3.5%). DISCUSSION: Mid-term results of
      this cementless straight taper at 10 year are at least equal to those of well
      performing cemented components, even in "high risk" groups of patients.
      Conversely, 28mm alumina-ceramic heads can reduce but not prevent the occurrence
      of PE-wear in such a healthy and active population. CONCLUSION: Press-fitting but
      not filling the femoral canal with rough titanium straight tapers like the
      Alloclassic-SL femoral component represent a promising alternative to modern
      femoral cementing technique in primary THA. Improvement is expected through the
      use of more wear resistant bearing surfaces.

PMID- 11845085
TI  - [Anterior iliopsoas impingement after total hip arthroplasty: diagnosis and
      conservative treatment in 9 cases].
AB  - PURPOSE OF THE STUDY: Impingement of the iliopsoas muscle due to a protruding
      acetabular component is an uncommon cause of pain after total hip arthroplasty.
      Diagnostic signs may be misleading and therapeutic management has varied, leading
      to divergent findings reported in the literature. The purpose of this prospective
      work was to determine the frequency of groin pain due to iliopsoas impingement
      (with or without an identified causal mechanism) in patients with painful total
      hip arthroplasties and to identify diagnostic criteria that can be used to
      determine the appropriate therapeutic strategy. MATERIAL AND METHODS: This
      prospective study was conducted between 1998 and 2000 and included 206 painful
      total hip arthroplasties. From this series, we excluded cases where pain was
      related to loosening (139 cases, 67%), infection (45 cases, 21.7%), bursitis on
      trochanteric sutures (2 cases, 1%), and aortic aneurysm with gluteal claudication
      and resulting from a lumbosacral disorder (10 cases, 4.8%). This left 9 cases
      (4.3%) with a clinical picture suggestive of iliopsoas impingement. These 9
      patients (mean age 50 years, age range 38 - 65) had 8 uncemented press-fix cups
      and 1 cemented cup with an acetabular mesh. Mean delay to the development of pain
      after the arthroplasty procedure was 7.3 months (1 - 48 months). The most
      suggestive clinical sign was groin pain triggered by active flexion of the hip
      and flexion of the hip against force with a painful arc measuring 30 degrees to
      70 degrees. None of these 9 patients had any sign of material loosening and
      puncture aspiration ruled out infection. The final diagnosis was confirmed by
      sedation of pain after extra-articular infiltration at the anterior border of the
      cup (overhanging cup in 6/9 cases) under computed tomographic guidance. RESULTS:
      Infiltrations with xylocaine and long-release corticosteroids led to complete
      sedation of pain in 4 out of 9 patients and partial sedation in 1 other.
      Recurrent pain led to terminal tenotomy of the iliopsoas in 4 patients, that
      provided total sedation in 3 and partial sedation in 1. In all, successful pain
      relief was achieved in 7 out of 9 cases: 4 after infiltration (repeated in 1
      cases) and 3 after tenotomy. At last follow-up physical examination has not
      identified any loss of flexion force. DISCUSSION AND CONCLUSION: Irritation of
      the iliopsoas muscle can be the cause of pain in 4.3% of patients experiencing
      pain after total hip arthroplasty. The delay to symptom onset is variable but
      there appears to be a pain-free period after implantation. An anatomic element
      (anterior cup overhang) is not necessary for diagnosis since the infiltration
      test was positive in 1 out of 3 cases without any identified acetabular factor.
      The infiltration test is an important element for positive diagnosis and should
      be the first therapeutic measure taken. We achieved success in 4 out of 9 cases.
      Tenotomy is indicated in case of recurrence, providing complete cure in 3 out of
      4 cases in our series. Cure may be achieved without changing the cup by simple
      infiltration or tenotomy of the iliopsoas that led to complete cure in 7 out of 9
      cases in our series, even in patients with an overhanging cup (6 out of 9 cases).
      An elective procedure might be indicated if a specific anomaly is identified
      (overly long screw, cement leakage) or for a screwed cup. The infiltration test
      should however be performed beforehand to confirm the diagnosis.

PMID- 11845086
TI  - [Iliopsoas impingement in 12 patients with a total hip arthroplasty].
AB  - PURPOSE OF THE STUDY: We report 12 cases of iliopsoas impingement, an under
      recognized cause of hip pain in total hip arthroplasty patients. MATERIAL AND
      METHODS: Between January 1998 and October 2000, we diagnosed 12 cases of
      iliopsoas impingement among 280 total hip arthroplasty patients with hip pain
      (4.3%). Our population was composed of 9 women and 3 men aged 62 to 80 years
      (mean 72 years). Nine patients had a first intention arthroplasty and 3 had a
      revision prosthesis. Delay from implantation to diagnosis of impingement ranged
      from 6 months to 5 years. Common cases of pain after hip arthroplasty, infection,
      loosening, were ruled out in all cases. A standard x-ray series including an AP
      view of the pelvis, an AP view of the hip and a surgical false-lateral view of
      the hip as well as a CT scan were obtained when iliopsoas impingement was
      suspected. The CT series extended from the lower part of the acetabulum through
      the fixation screws. RESULTS: Pain had been observed immediately after
      implantation in 10 cases (83%) and in 2 cases (17%) 3 to 5 years later. These
      patients did not have to use crutches when pain started to develop. Pain
      projected anteriorly and was always exaggerated when moving from the sitting
      position to the upright position and when going up stairs. In one patient,
      palpation revealed a mass in the groin that corresponded to a massive iliopsoas
      bursitis. Two non-pathognomonic physical signs were found in all cases: groin
      pain induced by active flexion against force in the lateral reclining position
      and at hip extension, and pain in the dorsal reclining position at deflexion of
      the hip, starting at 45 degrees. The standard AP views showed evidence of
      defective anteversion of 4 press fit cups, 1 off-centered screwed cup and 3
      oversized cups. The CT scan demonstrated that the impingement involved the
      anterior border of the cup applied against the iliopsoas tendon in 8 cases either
      due to anterior uncovering in a dysplasic hip or anterior cup overhang. In 4
      cases the cup fixation screws protruded anteriorly in front of the ilion and came
      in contact with the posterior aspect of the iliopsoas muscle. A bursitis had
      developed in 50% of the cases. DISCUSSION: When infection and loosening have been
      ruled out, hip pain after total hip arthroplasty would suggest a possible
      impingement of the acetebular component on the iliopsoas muscle due to defective
      anteversion or centering, the use of oversized cups, and/or the use of fixation
      screws. We emphasize the importance of a correct position for the cup to avoid an
      overhanging anterior border and discuss the use of screwed cups for primary total
      hip arthroplasty and of oversized cups for revision procedures.

PMID- 11845087
TI  - [An unusual intratarsal dislocation: cuneonavicular and calcaneocuboid
      dislocation].
AB  - We report a case of tarsal dislocation with cuneonavicular dislocation associated
      with calcaneocuboidal dislocation. This dislocation is rare and severe because it
      causes disruption of both the medial and lateral columns of the foot. Early and
      prompt reduction of this rare injury was successful in this case and appears
      important.

PMID- 11845088
TI  - [Stiff painful spine in an 11-year-old girl with SAPHO syndrome].
AB  - Compression of the cervical spinal cord developed six months after the first
      signs of a stiff and painful spine in an 11-year-old girl. The clinical course,
      the association with other skeletal localization, particularly the sacroiliac
      joint and the roof of the acetabulum and the pathology findings of nonspecific
      inflammation led to the diagnosis of chronic recurrent multifocal osteomyelitis
      that can be included in a SAPHO syndrome (synovitis-acne-pustulosis- hyperostosis
      osteitis). We report the specific findings in our case and review the literature
      to define the nosology framework of this rather uncommon condition. To our
      knowledge, this is the first report of spinal cord injury in a child related to
      SAPHO syndrome.

PMID- 11845089
TI  - [Should we study the health of immigrant communities?].

PMID- 11845090
TI  - [Description of drinking water intake in French communities (E.MI.R.A. study)].
AB  - BACKGROUND: Assessment of risks associated with waterborne pollutants requires a
      good characterization of the exposure of individuals and populations. This
      characterization implies knowledge of pollutants' levels in water and their time
      variability, and also estimation of drinking water consumption. Several studies
      were conducted, mostly in North America, on levels of chemical contaminants or
      prevalence of pathogens. Few studies were conducted on drinking water intake of
      the general population. METHODS: This work, included within the E.MI.R.A study
      which was set up to assess waterborne infectious risks, describes in details
      daily drinking water consumption of 544 French volunteers. Data were collected by
      self-questionnaires. RESULTS: RESULTS differ according to the season. Tap water
      usage for food follows a normal distribution (arithmetic mean in winter=1.55 l/j,
      95% CI [0.20-2.90]; arithmetic mean in spring=1.78 l/j, [0.13-3.43]). Total
      drinking water intake follows a log-normal distribution (geometric mean in
      winter=1.60 l/j, standard deviation=1.73 l/j; geometric mean in spring=1.92 l/j,
      standard deviation=1.70 l/j). Tap water intake amounts to more than 80% of total
      drinking water consumption, and pure tap water (i.e not added, modified nor
      boiled) amounts to 42% of total drinking water. RESULTS are also displayed by
      age, and compared to other data available in the literature. CONCLUSIONS: This
      work provides data that can be used to develop risk assessment and
      epidemiological studies in the field of chemical or infectious risks in the
      context of France.

PMID- 11845091
TI  - [Pilot study for the registration of acute myocardial infarction in the Liege
      area (Belgium)].
AB  - BACKGROUND: In 1998, a permanent registry of myocardial infarction was developed
      in the Liege area (Belgium) to provide updated, exhaustive and validated data on
      the morbidity and mortality from cardiovascular causes, to define the patients'
      profile, to identify myocardial infarction therapeutic strategies and to complete
      and make comparisons with data collected in other parts of the country through
      methodologically identical registers. METHODS: All acute coronary events lethal
      or non lethal among individuals from both genders aged from 25 to 69 years and
      living in the area were registered according to the methodology developed for the
      MONICA project (Multinational Monitoring of Trends and Determinants in
      Cardiovascular Diseases) of WHO. The three main selected data sources were: death
      certificates, general practitioners and cardiologists, hospitals. The events were
      categorised according to symptoms, cardiac enzymes, electrocardiogram, history of
      chronic ischaemic heart disease and necropsy findings. RESULTS: The coronary
      event rates were 283/100,000 in men and 102/100,000 in women. The case fatality
      rate, 28 days after the onset of the symptoms, was 30.6% for men and 36.2% for
      women, and 77.5% of deaths occurred in the first 24 hours after the onset of the
      symptoms. CONCLUSION: The development of a myocardial infarction register at a
      regional level requires the involvement of all health professionals dealing with
      that pathology. Such register has valuable public health interests, providing
      exhaustive and validated data on the pathology and its evolution as well as
      useful information for improving therapeutic strategies and developing adapted
      preventive measures.

PMID- 11845092
TI  - [Preliminary information to patients and presentation by Burkinabe physicians of
      the results of HIV detection test in Burkina Faso].
AB  - BACKGROUND: The action of individuals and their family is determining in the
      result of AIDS control and the knowledge of people's serological situation
      facilitates their involvement in AIDS control. This study was carried out in
      order METHODS: A transversal investigation through a self-administered anonymous
      questionnaire was carried out among the 250 Burkinabe physicians working in a
      public, private or religious health care sector. The questionnaire was sent by
      mail, attached to a response coupon. A response of 74% was obtained. RESULTS:
      Seventy seven physicians, that is 48.7% of the sample, informed patients who were
      likely to be HIV infected about their intention to ask for an HIV test. Seventy
      five physicians, that is 47.5% of the sample informed patients on the results of
      their serological tests on HIV infection. The characteristics of physicians who
      informed customers on the results of their serological test were similar to those
      of physicians who informed their patients on the demand for test concerning them.
      There were often specialists, physicians with long experience in medical practice
      and physicians more involving in curative consultations than in preventive ones
      (respectively 54.7% versus 23.3%, p=0.002). CONCLUSIONS: These results show the
      necessity of providing young physicians with counselling training, especially
      general practitioners who should be working in prevention services. Moreover,
      they constitute a basis for an objective discussion between physicians working in
      hospital, officials in charge of the national program for AIDS control and
      medical training schools.

PMID- 11845093
TI  - [Maternal weight gain during pregnancy in various immigrant communities living in
      France].
AB  - BACKGROUND: The aim of this study was to estimate, by geographic origin, the
      average situation of pregnant women who recently immigrated into the Paris area,
      using weight gain during pregnancy and infant birth weight. METHODS: The clinical
      files of 559 pregnant women who attended the antenatal clinic at the Lariboisiere
      Hospital (Paris) in 1997 and gave birth in this same hospital were analyzed. The
      mothers had immigrated from North Africa, Sub-Saharan Africa, Sri Lanka, China
      and metropolitan France. The successive body mass indexes were calculated for
      each woman, as well as the increase of this index during the first semester of
      gestation, until the third trimester and during the entire gestation. Averages in
      studied communities were compared with those of the non-immigrant population
      attending the same hospital department. The birth weights of infants from the
      different communities were compared with those of children born to non-immigrant
      mothers. RESULTS: Women from the various communities studied (with the exception
      of the Turkish community) showed a lower gestation weight gain than non-immigrant
      French women. Independently of the pregestational weight, weight gain during
      pregnancy accounted for 20% of the initial weight among women from North Africa,
      Turkey and China who gave birth to children whose birth weight was not
      significantly different from that of the non-immigrant French children. The mean
      weight gain corresponded to 15.8% of the pregestation weight in Sub-Saharan women
      and 18% in Sri Lanka women. Birth weights of children in these two communities
      were significantly lower than the French reference population. Compared with the
      weights observed in their original country, the frequency of low birth weight was
      lower and the mean birth weight was higher. CONCLUSION: Women coming from North
      Africa, Sub-Saharan Africa, and Asia who recently immigrated into France gave
      birth to children of satisfactory birthweight. The number of low birth weights
      decreased to the frequencies observed in their original countries. Irrespective
      for their reasons for immigrating, immigrant families living in France have
      newborns with a sufficient birth weight to allow satisfactory growth.

PMID- 11845094
TI  - [Survival of tetraplegic spinal cord injured persons after the first admission of
      a rehabilitation center and prognosis factors: a multicenter study of 697
      subjects in French centers].
AB  - BACKGROUND: We surveyed survival and prognosis factors in tetraplegic spinal cord
      injured persons (TSCI) after their admission to a physical medicine and
      rehabilitation center. METHODS: This multicenter study included 697 individuals,
      the entire cohort of patients admitted to three of the principal French centers
      caring for spinal cord injured persons from 1949 to 1997. The data set was drawn
      from the medical files and included data on the accident and its complications,
      social and demographic features, and the characteristics of the spinal injury.
      Survival data were obtained for all subjects from the official registries of
      their place of birth. Univariate (Kaplan-Meier) and multivariate (Cox regression)
      analysis was made to study links between these data and survival. RESULTS:
      Univariate analysis indicated that the principal variables significantly related
      to survival were: level of the lesion, age at the time of the accident, the cause
      of the accident, and the presence of a permanent tracheotomy or a depressive
      syndrome requiring medical care. Multivariate analysis showed that the risk of
      dying was 82% lower for persons who did not have a permanent tracheotomy. The
      risk declined by 92%, 89% and 69% for TSCI aged 20 years or less, 20-39 years and
      40-59 years respectively at the time of the accident compared with those aged
      more than 60 years. This risk was 37% lower for TSCI without depressive syndrome
      and 52% lower for persons injured at levels C6, C7, C8 compared with those
      injured at levels C2, C3, C4. CONCLUSION: Multivariate analysis showed that the
      principal prognosis factors for survival are the presence of a permanent
      tracheotomy, the age at the time of the accident, the presence of a depressive
      syndrome and the level of the lesion. No statistical improvement of survival was
      observed related with time (corresponding to the year of inclusion) but, over the
      study period, there was an increasing number of spinal cord injured person who
      survived with high lesions.

PMID- 11845095
TI  - [Association between work exposure to neurotoxic substances with workers'
      relationships with their social network].
AB  - BACKGROUND: This study explored the impact on family life and social relations
      that may result from symptoms associated with exposure to neurotoxic substances
      in the workplace. We assessed the associations between exposure to neurotoxic
      substances in the workplace, workers'mental health, and workers'relationships
      with their social network. METHODS: A sample of 53 workers and their spouse
      completed a series of questionnaires, an interview on work history, and a
      structured interview assessing their personal relationships. Exposure to
      neurotoxic substances in the workplace were assessed by an interview, using a
      semiquantitative classification system. Mental health was measured with the
      Profile of Mood States (POMS), and marital satisfaction with the Marital
      Adjustment Test (MAT). The social network's characteristics were assessed with
      the Northern California Community Study Interview Schedule (NCCS). The
      associations between exposure and social networks were assessed with regression
      analyses. RESULTS: There were no associations between exposure and marital
      satisfaction. However, we found a negative association between workers'exposure
      and degrees of overlap between husbands' and wives' social networks (Pearson's
      correlation r=-0.27; p<0.05) and a positive association between exposure and
      workers' dependency on their support network (r=0.46; p<0.01). CONCLUSION: The
      results are discussed in terms of variables potentially linking exposure to
      social relationships as well as in terms of couples' vulnerability to marital
      distress among exposed workers.

PMID- 11845097
TI  - [Selection effects in epidemiological cohorts: nature, causes and consequences].
AB  - Selection effects in cohort studies occur when the population observed over time
      differs from the target population due to the inclusion or follow-up of the
      subjects. Selection effects may bias the estimation of the frequency of the
      disease and of the exposure of interest, or the estimation of the association
      between disease and exposure. In industrial cohorts, where subjects are not
      volunteers, the reasons why they were hired and they stay working in a company
      are often linked with lifestyle factors or health problems that can be associated
      with the diseases or the exposures of interest. This phenomenon is known as the
      "healthy worker effect". When the cohort includes volunteers, other selection
      effects associated with the reasons why the individuals participate in the study
      and stay in the cohort may occur. The time course of both exposure of interest
      and health status during follow-up may also be associated with the probability of
      staying in the cohort. We describe the main components of the various selection
      effects associated with inclusion of the subjects at baseline, with their follow
      up during the observation of the cohort, and we examine the main components of
      the selection effects and their consequences.

PMID- 11845096
TI  - Initial results of a study into the effectiveness of breast cancer screening in a
      population identified to be at high risk.
AB  - BACKGROUND: Women are frequently referred to genetic clinics because of a family
      history of breast or ovarian cancer, conferring a moderate increased risk of the
      disease, but not sufficient in itself to indicate gene mutation analysis. One
      possible management strategy is to offer regular mammographic screening, possibly
      earlier in life and more frequently than in the general population. This strategy
      is used in many parts of the UK, although it has not been formally evaluated.
      METHODS: In this paper we present some early results on the effectiveness of a
      programme of mammography in 2,998 women aged 19-71 with a moderate family history
      of breast cancer in Manchester. We estimated the test and programme sensitivity
      and sojourn time, using different statistical methods. RESULTS: Fifty breast
      cancers were diagnosed. The incidence rate observed was 4.46 per thousand person
      years. The incidence expected from the segregation analysis of Claus et al. was
      3.75 per thousand person-years. Screen-detection rates at first and subsequent
      screens were 5.00 and 4.93 per thousand respectively. Interval cancer incidence
      in the first year following a negative screen was 0.91 per thousand person-years.
      Screening test sensitivity was estimated conservatively as 83%, programme
      sensitivity as 70%. CONCLUSIONS: Early indications are that the programme is
      likely to be effective. Further follow-up, analysis of tumour size, node status
      and malignancy grade, and subsequent mortality from breast cancer is required to
      confirm this.

PMID- 11845099
TI  - [Asbestos: is there still a future for epidemiology?].

PMID- 11845100
TI  - [The population treated in the general psychiatric sector in 1993 and 1998.
      Clinical and demographic evolution].
AB  - BACKGROUND: The French information system in public psychiatry sectors does not
      collect morbidity data for the population being treated, estimated as more than a
      million persons in 1997. Consequently, two surveys were financed by the
      "Direction Generale de la Sante" and carried out in 1993 and 1998 in order to
      specify clinical, social and demographic characteristics of the patients. These
      surveys allowed a follow-up of evolutions according to the pathology and mode of
      treatment in a context where outpatient treatments are becoming increasingly
      frequent. METHODS: A census of the patients was made at a given moment, between
      one and fifteen days according to the mode of treatment. One sector out of two
      was surveyed, using a systematic selection process. The ICD-10 was used for
      diagnosis reference. The same methodology was applied in 1993 and 1998.
      Comparisons were made with the data supplied by the sectors annually and with the
      data concerning the general population in order to calculate rates per age
      groups. RESULTS: Between 1993 and 1998, the number of patients increased by +37%
      in outpatient care, and in part time care, and decreased by -12% in full time
      care. Rates for patients increased for all age groups in outpatient and part time
      care, more particularly for the 35 to 49 years old. Conversely, rates decreased
      in full time care, above all for patients over seventy. In each mode of
      treatment, the number of patients presenting mood disorders and neurotic
      disorders increased more than the average, and the proportion of patients with
      organic mental disorders and mental retardation decreased. Evolutions were
      different according to the mode of treatment schizophrenia, schizotypal and
      delusional disorders, and disorders of adult personality and behaviour.
      CONCLUSIONS: Recourse to outpatient care and part time care increased
      considerably over five years but evolutions were markedly different from one
      diagnosis to another. In full time care, the decrease more particularly concerned
      certain pathologies and age groups. Three phenomena, with possible interactions,
      could explain the evolutions observed: the population liable to have recourse to
      psychiatric care is increasing, health policies have changed and care supply has
      become diversified, and recourse to psychiatric care is now increasingly
      accepted.

PMID- 11845101
TI  - [Malignant mesothelioma in Basse-Normandie, a French population study.
      Descriptive analysis, prognostic factors and survival].
AB  - BACKGROUND: Malignant mesothelioma is a pleural and/or peritoneal tumor closely
      related to asbestos exposure, and its incidence should continue to increase
      during the first two decades of the 21(rst)century. The main prognostic factors
      described for this tumor are older age, sex, tumor stage and histological type.
      The aim of this study was to assess the incidence of pleural and peritoneal
      malignant mesothelioma in the County of Basse-Normandie (France), as well as
      their epidemiological characteristics, and the prognostic factors related to
      survival duration. METHODS: Cases were identified through repeated inquiries
      among all chest physicians and pathologists of the County of Basse-Normandie. A
      special care was taken in the validation of the diagnosis of each case. Incidence
      of mesothelioma was determined according to sex and age (5 years categories).
      Qualitative and quantitative variables were compared with the use of chi-square
      or Student's t tests respectively. Survival rate was calculated by Kaplan-Meier
      method, and prognostic factors were studied by means of Cox model. RESULTS: Study
      population consisted in all 80 malignant mesothelioma cases diagnosed in Basse
      Normandie between the 1(rst) of September 1995 and the 31(rst) of August 1999.
      Annual incidence rates of pleural mesothelioma were 1.1/100 000 in men and
      0.23/100 000 in women; annual incidence rates for peritoneal mesothelioma were
      0.21/100 000 in men and 0.13/100 000 in women. Asbestos exposure was present in
      63 cases (78.8%). The study of geographic distribution of mesothelioma cases
      revealed the influence of the main asbestos industrial settings, as well as the
      numerous scattered cases related to other occupational exposure. Mean survival
      duration was 9 months for pleural mesothelioma and 5 months for peritoneal
      mesothelioma. After adjustment on age, death risk was higher in asbestos-exposed
      than in non asbestos-exposed cases. CONCLUSION: This study confirms that
      malignant mesothelioma is closely related to asbestos exposure, but not only in
      main asbestos industrial settings. It suggests that asbestos exposure may take
      place among prognostic factors of this tumor.

PMID- 11845102
TI  - [Relation between uricemia and total, cardiovascular and coronary mortality in
      both genders of non-selected sample of the Belgium population].
AB  - BACKGROUND: Despite more than 40 years of research on the prognostic value of
      hyperuricemia in relation to all-causes cardiovascular and coronary mortality, no
      clear consensus appears in the medical literature. Moreover, the observed
      relationship between hyperuricemia and the incidence of coronary heart disease
      mortality is related to gender. However, prospective studies including both
      genders are rare. METHODS: A prospective study was conducted in a random sample
      of 5225 males and 4476 females from the Belgian population aged 25 to 74 years at
      the initial survey and followed for 10 years for all-causes and specific
      mortality. RESULTS: The number of observed total, cardiovascular, and coronary
      heart disease deaths were 648 and 239, 150 and 225, and 96 and 51 in males and
      females respectively. At multivariate analysis, uricemia was significantly
      correlated with all-causes mortality in males whereas a tendency was observed in
      females. The same diverging association was observed for cardiovascular
      mortality. However, for coronary heart disease mortality, there was a very
      significant correlation only in females. CONCLUSIONS: Our findings confirm the
      observed gender-related differences in the relation of hyperuricemia with all
      causes and coronary heart disease mortality. We propose possible pathogenic
      mechanisms concerning the relationship with coronary heart disease mortality
      observed only in females.

PMID- 11845103
TI  - [Cost of cardiovascular risk factor prevention in middle-aged French men. The
      PRIME study].
AB  - BACKGROUND: Little is known regarding the cost of cardiovascular risk factor
      prevention in France. In this study, we assessed the cost of antihypertensive and
      hypolipidaemic drug treatment in middle-aged French men without history of
      coronary heart disease. METHODS: A cross-sectional study was conducted between
      1991 and 1993 in 1606 subjects treated for hypertension or dyslipidaemia from the
      three French centres participating in the PRIME study. The daily cost of
      treatment (in Euros) was assessed using data from the Agence Nationale du
      Medicament. RESULTS: Mean daily cost of hypertension was 0.65 euro per patient;
      after multivariate adjustment, obese subjects had a mean daily cost of 0.74+/
      0.03 euro (adjusted mean +/- standard error) versus 0.66+/-0.03 euro for non
      obese (p<0.001). Only 58% of hypertensive subjects were adequately controlled,
      and this percentage was higher in the Toulouse centre (80.1%) than in Lille
      (44.4%) or Strasbourg (50.2%), p<0.001. Fibrates were the most frequently
      prescribed hypolipidemic drug; nevertheless, prescription of statins was higher
      than fibrates in the Toulouse centre, which led to a higher mean daily cost for
      dyslipidaemia, which was further confirmed by multivariate adjustment: 0.59+/
      0.05 euro (adjusted mean +/- standard error) in Toulouse versus 0.44+/-0.04 euro
      in Lille and 0.44+/-0.04 euro in Strasbourg. Only 54% of treated dyslipidemic
      subjects had their lipid levels within normal values, and this percentage was
      significantly lower (44%) in Strasbourg than in Lille (58%) or Toulouse (59%)
      (p<0.001). CONCLUSION: The prescription of anti-hypertensive or hypolipidemic
      drugs differs according to centre, leading to significant differences in mean
      daily cost of treatment. A considerable percentage of treated subjects is not
      adequately controlled, with possible consequences at the economical level.

PMID- 11845104
TI  - [Description of unused drugs collected in pharmacies in the Puy-de-Dome region in
      France].
AB  - BACKGROUND: An unused drug (UD) is defined as a drug which is purchased, after
      prescription or not, but which is not taken. Public health campaigns in France
      have requested people to return these drugs to their pharmacy. To data, few data
      have been available concerning the quantity of collected UD and their potential
      re-use. A study was performed in the pharmacies of the Puy-de-Dome region in
      France to describe the UD circuit. METHODS: A random sample of 1 out of 5
      pharmacies in the Puy-de-Dome region (France) were defined by single level
      stratified sampling from the list of all pharmacies operating in the region. An
      exhaustive record of all UD people brought back to these pharmacies was made in
      1998 during three 1-week periods. The following data were recorded for each UD:
      the name of the drug, the pharmaceutical industry code (CIP), the price, the rate
      of social Security refunding, the mention of "free specimen" on the package, the
      inscription on the list of poisonous substances and on the list of essential
      drugs defined by the World Health Organization (WHO), the registration on the
      list of drugs reserved for hospital use, the packaging notice (opened or not),
      the therapeutic class, and the formulation. RESULTS: 10,254 US (717kg) were
      collected during the study period. The therapeutic classes of the UD were similar
      to those of drugs purchased in France. According to the selling price, these UD
      had an economic value of 405,845FF (i.e. 3.6% of Social Security refundings paid
      in the Puy-de-Dome region during this same period). Only 20% of the UD were
      potentially reusable for humanitarian purposes. Their estimated economic value
      was 87,456FF (i.e. 0.78% of the annual Puy-de-Dome Social Security refunding).
      Moreover, 43.4% of the reusable drugs were on the WHO list of essential drugs.
      CONCLUSION: Although the volume of collected UD is high, use by humanitarian
      associations is on the decline because of the cost of collection and low economic
      yield. Furthermore, UD must be collected in a systematic manner to preserve the
      environment and prevent domestic accidents.

PMID- 11845105
TI  - [Management of multidimensional clinical scores: which solutions for items
      aggregation?].
AB  - BACKGROUND: Clinical evaluation is a multifactorial process producing as many
      clinical scores as there are clinical dimensions. For a medicoeconomical analysis
      however, a single global score would be most useful. The aim of this work was to
      examine methods allowing relative quantification of items on multidimensional
      clinical scores in order to determine an appropriate solution for weighted items
      aggregation. METHOD: Several techniques for item weighting, developed as part of
      a multi-criteria decision-making tool (AMCD Aide Multi-Critere a la Decision),
      were examined. Two methods were applied to multidimensional assessment of
      disability in order to estimate the weight that should be assigned to each of its
      six items before aggregation in a unique score. The AHP method was used with an
      interview of 20 functional rehabilitation specialists. The Diakoulaki method was
      based on the observation of thirty patients with chronic back pain and in thirty
      patients with vascular hemiplegia. RESULTS: The three weighting schemes were very
      different from the uniform weighting and were not correlated with each other. The
      items best weighted by the AHP method were "physical independence" and
      "mobility". For the Diakoulaki method, they were "social integration" and
      "economic independence" for the chronic back pain patients, and "awareness of the
      outside world" and "economic independence" for the vascular hemiplegia patients.
      Application of these three weighting schemes to theoretical patients produced
      very different assessments of global disability. CONCLUSIONS: Weighting schemes
      are useful to quantify the relative importance of individual clinical items. The
      choice of the weighting method is determinant and depends on the objective of the
      investigator. If the objective is a global score, the first step is to estimate
      the weight of the individual items, either when applying a validation process for
      a new multidimensional clinical score, or secondarily to adapt a validated score
      to a particular protocol.

PMID- 11845106
TI  - [Required procedure for nominal data files processing in biomedical research].
AB  - To date, biomedical research using nominal data files for the data collection,
      data acquisition or data processing has had to comply with 2 French laws (Law of
      December, 20, 1988, modified, relating to the protection of patients
      participating in biomedical research, and the Law of January, 6, 1978, completed
      by the Law of July 1, 1994 n degrees 94-548, chapter V bis). This later law
      dictates rules not only for the establishment of nominal data files, but also
      confer individual rights to filed persons. These regulations concern
      epidemiological research, clinical trials, drug watch studies and economic health
      research. In this note, we describe the obligations and specific general and
      simplified procedure required for conducting biomedical research. Included in the
      requirements are an information and authorization procedure with the local and
      national consultative committees on data processing in biomedical research
      (CCTIRS, Comite Consultatif sur le Traitement de l'Information en Recherche
      Biomedicale, and CNIL, Commission Nationale Informatique et Libertes).

PMID- 11845107
TI  - [Using discharge abstracts as a tool to assess a regional perinatal network].
AB  - To assess the regional perinatal network of Burgundy (20 obstetrical units;
      18,000 births/year), discharge abstracts are collected for all mothers and all
      neonates. Discharge abstracts are expanded with some additional data. According
      to the French law, data are rendered anonymous in each hospital before their
      transmission to the teaching hospital for statistical analysis. The linkage of
      all anonymous information concerning a patient is obtained. Moreover, this
      specific procedure allows the linkage of data concerning each mother and her
      corresponding neonate. This study shows that after an expanded data quality
      control, the linkage between data of the mothers and their infants is obtained in
      99.8% of births.

PMID- 11845108
TI  - [Scooter injuries: beginning of an epidemic?].

PMID- 11845109
TI  - Role of color flow Doppler sonography in pre-operative diagnostics of the thyroid
      pathology.
AB  - BACKGROUND: The aim of this work is to demonstrate the high effectiveness of
      preoperative diagnosis by echotomographic study of thyroid nodules through color
      Doppler sonography integrated by B-mode. The authors performed both B-mode
      ultrasonography and color-Doppler sonography on 125 patients expecting total
      thyroidectomy surgical intervention, without a previous evaluation of a number of
      other already performed clinical and instrumental tests. After the intervention,
      we compared the histologic test with the data drawn from the ultrasound scan, in
      order to demonstrate that color-Doppler sonography is able to provide for
      additional diagnostic information in the preoperative period. METHODS: One
      hundred and twenty five patients with thyroid pathologies were examined by both B
      mode and color-Doppler sonography. Two diagnoses were made for each clinical
      case: the first supported by B-mode data, the second based on vascularity. Our
      aim was to check color-Doppler's ability to provide new information in the
      ultrasound diagnosis. All patients underwent a total thyroidectomy surgical
      intervention. The data were examined by K concordance test. RESULTS: Ultrasound
      data were compared with the histologic test, which showed 118 (97.4%) benign and
      7 (5.6%) malignant lesions. B-mode ultrasound test gave a correct diagnosis in
      115 (97%) out of 118 benign lesions and in 4 (57%) out of 7 malignant lesions,
      while 3 (2.5%) out of 118 cases were false positive and 3 (42.8%) out of 7 were
      false negative. In those cases showing a wrong conventional ultrasound diagnosis,
      after the integration of B-mode with color-Doppler results, a decrease was
      recorded in both false negative and false positive. CONCLUSIONS: Even if no
      correspondence was found between the different aspects of blood flow and the
      histologic types of lesions, this experience proves that the color-Doppler test
      has a high predictive value of benignity in cases with pattern I II and IV, while
      lesions with pattern III should be more carefully examined, since both malignant
      and benign lesions belong to this group. From the data drawn from this study, we
      are able to infer that color-Doppler sonography is undoubtedly an advantage not
      only in terms of cutting the false negatives, but also in the aim of obtaining a
      higher effectiveness in the screening of goitrogenic pathology.

PMID- 11845110
TI  - The cell cycle in steroid hormone regulated proliferation and differentiation.
AB  - Steroid hormones mediate pleiotropic cellular processes involved in metabolism,
      cellular proliferation, and differentiation. The ability of the cell to respond
      to its hormonal environment is transduced by nuclear receptors (NRs) that bind
      both hormone and DNA. Hence, NRs represent a link between the external hormonal
      milieu and the genes that control cell physiology. Therefore, understanding the
      effects of steroid hormones on proliferation and differentiation requires a
      knowledge of the cell cycle, the interaction of NRs at the level of
      transcription, and the potential areas of cross-talk between these two.

PMID- 11845111
TI  - Use of alternatives to estrogen for treatment of menopause.
AB  - Women frequently chose alternatives to hormone replacement therapy (HRT) for
      treatment of menopause even though medical indications for estrogens may be
      present. Prior breast cancer or fear of breast cancer is a major consideration.
      This review of alternatives to estrogen discusses the evidence linking breast
      cancer to HRTs and compares potential risks and benefits of HRT to nonHRT
      alternatives for relief of vasomotor symptoms, vaginal atrophy, neurocognitive
      changes and prevention of heart disease and osteoporosis. Practical guidelines
      are suggested for use of alternatives for each problem.

PMID- 11845112
TI  - [Hypernatremia. Etiopathogenetic classification and description of a rare
      clinical case].
AB  - On the basis of a rare case of hypernatremia, the essential lines which allow a
      correct diagnostic and therapeutic approach to hypernatremia are underlined.
      Hypernatremia is classified according to the patient's state of hydratation and
      on the content of sodium as: hypovoloemic, euvolemic and hypervolemic. Even the
      concentrations of sodium in urine are often of great importance for a correct
      diagnosis. The patient studied suffered from hypernatremia, which is based on
      genetical factors. The state of dehydration, together with hypovolemia and acute
      tubular necrosis secondary to rhabdomyolisis, were the causes of hypernatremia.
      The above mentioned causes were resolved but an enterocutaneous fistula showed to
      be the cause, quite rare, of hypernatremia. It is suggested that this rare cause
      should always be mentioned when diagnosing hypernatremia; which it is important
      since this cause could be solved with an operation. All this was useless in our
      case since the patient had a drastic deterioration of his general clinical
      conditions.

PMID- 11845113
TI  - [Hashimoto's thyroiditis in "struma ovarii". Case report and review of the
      literature].
AB  - Struma ovarii, a teratoma in which thyroid tissue is the predominant or sole
      component account for 2.7% of all ovarian tumors. Pathogenesis is unclear. In
      addition to symptoms and signs caused by the presence of a mass, struma may be
      associated with a number of unusual clinical manifestations. Ascitis occurs in
      approximately one third of the cases, Meigs' syndrome occasionally and
      hyperthyroidism in only about 5% of cases. Thyroiditis is an occasional finding
      and Hashimotos' thyroiditis is rare in struma ovarii. The struma may resemble
      normal thyroid tissue, a thyroid adenoma or thyroid carcinoma. The treatment is
      surgical and the outcome generally favorable. This paper reports the first
      clinical case of a patient with Hashimoto's thyroiditis in a pure struma ovarii
      associated with positive specific antithyroid antibodies in the absence of
      symptoms and signs due to thyroid disease.

PMID- 11845114
TI  - "Hot" carcinoma of the thyroid. Case reports and comments on the literature.
AB  - It seems somewhat difficult to exactly define the real number of case reports
      concerning the association of hyperfunctioning thyroid node and carcinoma; the
      overall incidence of this condition seems, however, to be very rare. Different
      inclusion criteria are probably a fairly relevant cause of variability in the
      number of cases reported during the years. A basic classification scheme, as the
      one here reported, may be of help in characterizing the different possible
      conditions: 1. the coexistence of carcinoma and focally hyperfunctioning tissue
      in the same gland but at different locations (not uncommon); 2. the presence of
      such a large tumour mass that it can compete with normal tissue for tracer
      uptake, despite being hormonogenetically uneffective in itself; 3. the carcinoma
      located in the hyperfunctioning adenoma; 4. the real hyperfunctioning carcinoma,
      where coincidence between hyperfunctioning tissue and malignancy is complete
      (very rare). Two cases are reported here, respectively belonging to the third and
      fourth of these categories (the most challenging from a diagnostic point of
      view). The matter is intrinsically poor from a statistical standpoint: it is
      therefore difficult to draw definitive conclusions on the subject in operative
      terms. It is however felt that the systematic evaluation of oncological risk in
      thyroid nodes, occasionally recommended in the literature, may be cumbersome and
      not necessarily cost-effective.

PMID- 11845115
TI  - [The effect of instrumentation on original apical foramen shape using steel vs
      niti rotatory: computerized analysis].
AB  - BACKGROUND: A fundamental requirement to obtain a correct endodontic preparation
      depends on the respect, during cleaning and shaping, of the original morphology
      of the apical foramen, (AF), so that the filling material will form a complete
      seal. METHODS: In our previous studies, in order to verify if this presumption
      was respected using rotary NiTi instruments with cutting tip, we instrumented
      extracted teeth characterised by a different degree of root curvatures. Using a
      standardized system to replace the sample, the original shape of the apical
      foramen of each tooth was recorded using a computerised technique and then
      compared to the shape after instrumentation. The data showed differences on AF
      shapes depending on the degree of root canal curvatures. In fact, the teeth with
      straight canals showed the least alterations on the original AF shape; on the
      contrary, the teeth with curved canals showed apical foramen enlargement or
      transportation. Therefore, in the current study we aimed to compare the in vitro
      effects of stainless steel, (Flexofile, Dentsply Maillefer, Baillaigues,
      Switzerland), vs NiTi safe cutting tip (Quantec SC, (Tycom Dental, Irvine CA,
      U:S.A.), vs NiTi non cutting tip, (Quantec LX, Tycom Dental, Irvine CA, U:S.A.),
      instrumentation on original apical foramen shape. We used NiTi instruments
      according to standard technique suggested by Tycom, and hand steel files, to
      instrument the apical third, according to the Crown-Down technique. Working
      length was fixed at -0.5 from AF. RESULTS AND CONCLUSIONS: Our results suggested
      that in the presence of accentuated canal curves rotary Niti, with cutting tip,
      cause significantly more enlargement of the AF area. At the same time, we also
      observed that NiTi rotary files, with both cutting and non-cutting tip, cause
      eccentric enlargement of AF in curved canals. Therefore, NiTi engine-driven
      instruments should be used carefully in the presence of accentuated canal curves
      to avoid enlargement or transportation of AF, probably because rotary NiTi files
      may slip out of operative control, leaving a mark on the foramen shape. In the
      presence of severe curves, we suggest modifying the operative sequences by
      alternating rotary NiTi with hand NiTi or stainless steel instruments, especially
      in the preparation of apical third.

PMID- 11845116
TI  - [Polymerization exothermal reaction of dental prosthetic resin for temporary
      crowns. A comparative evaluation].
AB  - BACKGROUND: The aim of the present study is to evaluate the risk of a possible
      thermal stress of the pulpal tissue during the fabrication of a temporary crown
      when using the direct technique. METHODS: For this study, 7 different brands of
      acrylic resin including Acrylic type and Bis-Gma type have been tested. At this
      purpose one series of in vitro experimental trials were performed. The trials
      have evaluated the temperature increase inside the pulp chamber of an extracted
      tooth during the fabrication of a provisional crown. The temperatures reached by
      the resins tested were measured using a digital thermometer connected with a
      thermal probe. RESULTS: The temperatures measured during the experimental trials
      show a different ability by the 7 tested resins to produce heat. Indeed, while
      the polymethylmethacrylate resins show higher increments rate of temperature, the
      Bis-Gma resins produce less dramatic increase along with lower temperatures
      peaks. CONCLUSIONS: Testing the 7 different resins has proved that there is an
      actual risk to cause lesions to the pulpal tissue during the placement of a
      provisional crown when using the direct technique. The materials which show a
      reduced exothermal reaction are: IsoTemp and Protemp II.

PMID- 11845117
TI  - [Treatment of temporo-mandibular joint closed-lock using intra-articular
      injection of mepivacaine with immediate resolution durable in time (six months
      follow-up)].
AB  - BACKGROUND: The purpose of this study was to assess the value of intra-articular
      fluid injection under pressure, as a technique suggested for temporo-mandibular
      joint (TMJ) closed-lock treatment, and to determine if there is a persisting lock
      resolution in time. METHODS: Twelve patients were studied at our centre, with a
      diagnosis of TMJ closed-lock, not amenable with conventional therapies. All
      patients underwent a MRI scan, confirming the presence of anteriorly displaced
      disk. This technique is based on intra-articular injection of anaesthetic
      (mepivacaine cloridrate) under pressure, using the so called pumping technique,
      that allows an inferior distraction of the condyle. The study has a six months
      follow-up. After closed-lock resolution all patients underwent physiotherapy with
      guided mouth opening, for one month. RESULTS: Mandibular function (maximal mouth
      opening) increased on average of 20.2 mm after treatment, and of 21.1 mm six
      months later (p=0.00000; with p<0.005). Pain decreased on average from VAS=6.75
      to VAS=0.3 (p=0.00001; with p<0.005). The masticatory efficiency improved from
      VAS=5.25 to VAS=8.75 (p=0.002; p<0.005). Functional TMJ limitation level is
      significantly increased (p=0.002; p<0.005). Also, patient's efficacy judgement
      (mean value 3.58= good) and tolerability judgement (mean value 2.92=good)
      indicate that this therapy is well accepted. CONCLUSIONS: This technique is easy
      to perform, well tolerated and does not need specific instruments: it permits the
      resolution of TMJ closed-lock, decreases the pain and improves masticatory
      efficiency. All these effects persist in time. Subjects with recent closed-lock
      have an immediate and complete functional recovery while patients with chronic
      closed-lock do not.

PMID- 11845118
TI  - [In vitro antimicrobial activity of glutaraldehyde plus O-phenylphenol
      association (ratio 2:1)].
AB  - BACKGROUND: The correct use of antiseptics, disinfectants and sterilization
      processes to inactivate or remove micro-organisms is an essential component of an
      effective infection control program. To reach this result the use of phenolic
      detergent-disinfectants which work well as a presoak has always been suggested in
      lieu of sterilization involving submerging instruments in a properly prepared
      glutaraldehyde solution for about 6 to 10 hrs. This study investigated the in
      vitro effectiveness of disinfectant solution containing 2% glutaraldehyde and 1%
      o-phenylphenol. METHODS: The organisms used were purchased from the American Type
      Culture Collection (Escherichia coli ATCC 25922, Candida albicans ATCC 10231,
      Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus ATCC 25923,
      Staphylococcus epidermidis ATCC 12228), and from our clinical collection (Proteus
      mirabilis CH 14, Klebsiella oxytoca CH 22, Serratia liquefaciens CH 90). MIC and
      MBC were evaluated as testing solution for antimicrobial activity. The contact
      time studied between disinfectant and bacteria were 30 sec, 1, 2, 5, 10, 20 and
      30 min. RESULTS: The results showed that MIC values for most bacteria were 3.75
      mg/ml. The MBC values were similar or higher than the MIC. The disinfectant
      solution killed E. coli and C. albicans already after 10 min, but for S. aureus
      30 min was necessary. CONCLUSIONS: This study proved that this solution attained
      the sterilization of surgical instruments in good timing and at low cost.

PMID- 11845119
TI  - [Request of dental care and periodontal treatment needs in a population sample of
      Palermo].
AB  - BACKGROUND: The organisation of periodontal health prevention programmes must
      take into account the public level of awareness of the periodontal diseases. The
      aim of the present investigation was to assess the relationships between the
      request of dental care and the periodontal treatment needs in a population sample
      of Palermo. METHODS: The study population consisted of 554 out-patients,
      consecutively examined during 18 months (January 1999 to June 2000) at the
      Palermo University Department of Oral Sciences. All participants answered a
      written questionnaire concerning the cause for the request of dental care and
      periodontal symptoms. Periodontal treatment needs were assessed using the
      Community Periodontal Index of Treatment Needs (CPITN). RESULTS: Statistical
      analysis (Chi-Square Test, Fisher's Exact Test) showed significant discrepancies
      between the request of dental care and the periodontal treatment needs, poor
      awareness of periodontal diseases and low perception of their symptoms by the
      patients. CONCLUSIONS: These findings showed that the awareness of periodontal
      diseases by the population examined is poor. This could be due either to the lack
      or failure of public education programmes on periodontal health. Yet, it could be
      related to an inadequate dentists' awareness of the periodontal diseases. Such
      findings should be considered in the planning of periodontal health programmes in
      relation to the population of Palermo.

PMID- 11845120
TI  - [Periodontic-endodontic lesions: diagnostic and therapeutic indications].
AB  - The presence of connections between periodontium and endodontium can lead to the
      diffusion of an infection from one apparatus to another. The involvement of both
      periodontium and endodontium is defined as Combined Periodontic-Endodontic
      lesions. This definition is not based on the initial etiology of the lesion and
      either the endodontic or periodontal lesion may be the cause or the result of the
      other or both may develop independently. The lesions must be correctly diagnosed
      for the best therapeutic approach. The diagnosis is based on clinical symptoms
      and radiographic analysis; clinical signs must show the presence of periodontal
      probing and pulpal necrosis. Radiographic examination can confirm the involvement
      of both periodontium and endodontium only if the lesion is present on the mesial
      and distal part of the diseased tooth; in the case of a palatal/lingual or
      vestibular lesion such evidence will not be detectable. The therapeutic approach
      is always based on an initial endodontic treatment followed, if needed, by the
      proper periodontal treatment.

PMID- 11845121
TI  - [Dental management of patients with cardiovascular disease].
AB  - Authors present the management of patients affected by cardiovascular disease
      undergoing oral surgical treatment. Oral surgery may influence the health of
      these patients because of three factors: psychological stress, anesthesia and
      daily pharmacological therapy. Dentists have to know and apply preventive rules
      to avoid the risks of medical complications during surgical treatment, they also
      have to be able to manage cardiological emergencies wherever they occur.

PMID- 11845122
TI  - The Palio.

PMID- 11845124
TI  - Quantification of myocardial glucose utilization by PET and 1-carbon-11-glucose.
AB  - BACKGROUND: Measurements of the rate of myocardial glucose utilization (rMGU)
      play a key role in the assessment of alterations in myocardial substrate
      metabolism in normal and abnormal cardiac states. In this study we determined
      whether rMGU could be quantified by positron emission tomography (PET) and 1
      carbon-11-glucose. METHODS AND RESULTS: Twenty dogs were studied with a variety
      of interventions including fasting (n = 5), hyperinsulinemic-euglycemic clamp at
      rest (n = 6), clamp and phenylephrine (n = 5), and clamp and dobutamine (n = 4).
      Measurements of myocardial blood flow and rMGU were made by PET with oxygen-15
      water and 1-C-11-glucose, respectively. Arterial-coronary sinus sampling was
      performed to measure rMGU by the Fick method. Values for rMGU ranged from 50 to
      2436 nmol/g/min. Myocardial 1-C-11-glucose images of high quality were obtained.
      There was a close and direct correlation between values for rMGU measured by PET
      and those measured directly (y = 0.86 x + 112, r = 0.98, P <.0001). The
      coefficient of variation for the regional estimates of rMGU ranged from 11.3% +/-
      7.4% during clamp at rest to 16.3% +/- 8.4% during clamp with phenylephrine.
      CONCLUSIONS: It now appears possible to quantify myocardial glucose utilization
      by PET with 1-C-11-glucose. This method should become a valuable tool in the
      assessment of alterations in myocardial glucose metabolism in both normal and
      abnormal myocardium.

PMID- 11845125
TI  - Segmental pattern of myocardial sympathetic denervation in idiopathic dilated
      cardiomyopathy: relationship to regional wall motion and myocardial perfusion
      abnormalities.
AB  - BACKGROUND: Iodine 123-labeled metaiodobenzylguanidine (MIBG) has been used to
      study cardiac adrenergic nerve activity. Cardiac MIBG uptake is diminished in
      patients with heart failure. However, it is not known how this reduction is
      related to regional abnormalities of myocardial wall motion or perfusion. METHODS
      AND RESULTS: We studied 24 patients with idiopathic dilated cardiomyopathy
      (ejection fraction <45%) and 15 healthy control subjects using I-123 MIBG cardiac
      imaging, echocardiographic assessment of wall motion abnormalities, technetium
      99m sestamibi perfusion scintigraphy, and hemodynamic assessment. Cardiac MIBG
      was significantly correlated with ejection fraction (r = 0.67), cardiac index (r
      = 0.57), left ventricular wall motion score index (r = -0.68), and systolic wall
      stress (r = -0.61). MIBG was lower in patients than in control subjects (1.43 +/-
      0.19 vs 2.05 +/- 0.02; P <.01), whereas the washout rate was higher (P <.01).
      Moreover, a significant correlation was found between the reduction in MIBG
      uptake and the severity of echocardiographic wall motion abnormalities in the
      anterior wall (r = 0.543), apex (r = 0.530), and septum (r = 0.675), as well as
      with the severity of decrease in resting myocardial perfusion in the anterior
      wall (r = 0.480) and septum (r = 0.580). CONCLUSIONS: Patients with idiopathic
      dilated cardiomyopathy show not only global but also regional abnormalities of
      cardiac sympathetic innervation. The severity of these changes is partially
      correlated with abnormalities of regional wall motion and myocardial perfusion.

PMID- 11845126
TI  - Risk stratification in patients with remote prior myocardial infarction using
      rest-stress myocardial perfusion SPECT: prognostic value and impact on referral
      to early catheterization.
AB  - BACKGROUND: Little is known about the prognostic value of myocardial perfusion
      single photon emission computed tomography (SPECT) in patients with remote prior
      myocardial infarction (MI). METHODS AND RESULTS: We identified 1413 consecutive
      patients with remote prior MI who underwent rest-stress myocardial perfusion
      SPECT. Semiquantitative visual analysis of 20 SPECT segments was used to define
      the summed stress, rest, and difference scores. The number of non-reversible
      segments was used as an index of infarct size. During follow-up (>or=1 year), 118
      hard events occurred: 64 cardiac deaths (CDs) and 54 recurrent MIs. Annual CD and
      hard event rates increased significantly as a function of SPECT abnormality. For
      summed stress scores less than 4, 4 to 8, 9 to 13, and more than 13, the annual
      CD rates were 0.4%, 0.9%, 1.7%, and 3.5%, respectively (P =.002). Patients with
      small MI (<4 non-reversible segments) and no or mild ischemia (summed difference
      score <or=6) had an annual CD rate of 0.6%. Patients with small MI and moderate
      or severe ischemia had an annual CD rate of 1.6%, and those with large MI (>or=4
      non-reversible segments) had moderate to high annual CD rates (3.7%-6.6%)
      regardless of the extent of ischemia. Nuclear testing added incremental
      prognostic information to pre-scan information. Compared with a strategy in which
      all patients are referred to catheterization, a strategy that referred only those
      patients with a risk for CD of greater than 1% by myocardial perfusion SPECT
      resulted in a 41.6% cost savings. CONCLUSIONS: Myocardial perfusion SPECT adds
      incremental value to pre-scan information and is highly predictive and cost
      efficient in the risk stratification of patients with remote prior MI. Patients
      with normal or mildly abnormal scan results or small MI in combination with
      absent or mild ischemia have a low risk for CD.

PMID- 11845128
TI  - Discordance between dipyridamole stress Tc-99m sestamibi SPECT and coronary
      angiography in patients with Kawasaki disease.
AB  - BACKGROUND: Kawasaki disease is an acute vasculitis syndrome of unknown etiology
      that mainly affects the coronary arteries. The purpose of this study was to
      assess the agreement between dipyridamole stress technetium 99m sestamibi single
      photon emission computed tomography (SPECT) and coronary angiography in these
      patients. METHODS AND RESULTS: Forty-one consecutive patients (29 boys and 12
      girls) who underwent coronary angiography were studied prospectively. Their ages
      at onset of the disease ranged from 2 months to 4.8 years (mean +/- SD, 1.9 +/-
      1.3 years). Their ages at the time of the study ranged from 8 months to 15.3
      years (6.2 +/- 4.4 years). The duration between symptom onset and the study
      ranged from 2 months to 12 years (4.3 +/- 4.0 years). All patients underwent
      dipyridamole stress Tc-99m sestamibi SPECT within 1 month of their angiographic
      studies. They were divided into 3 groups according to coronary angiography
      findings. Group A consisted of 2 patients (1 boy and 1 girl, aged 10.3 and 1.9
      years, respectively) with coronary stenoses who also had aneurysms. Group B
      consisted of 10 patients (8 boys and 2 girls, aged 0.7-15.3 years [mean, 3.8
      years]) with coronary aneurysms. Group C consisted of 29 patients (20 boys and 9
      girls, aged 1.2-13.8 years [mean, 7 years]) with normal coronary angiograms. Two
      patients in group A (100%), 3 of 10 patients in group B (30%), and 19 of 29
      patients in group C (65.5%) had myocardial perfusion defects. There was poor
      agreement between Tc-99m sestamibi SPECT and coronary angiography for detecting
      coronary stenoses (kappa = 0.07; P =.222) and aneurysms (kappa = -0.184; P
      =.158). CONCLUSION: Significant discordance exists between Tc-99m sestamibi SPECT
      and coronary angiography in patients with Kawasaki disease.

PMID- 11845127
TI  - Tetrofosmin imaging in the detection of myocardial viability in patients with
      previous myocardial infarction: comparison with sestamibi and Tl-201
      scintigraphy.
AB  - BACKGROUND: Technetium 99m tetrofosmin has been introduced as a myocardial
      perfusion agent, providing similar results to those of thallium 201 and sestamibi
      in the identification of patients with coronary artery disease. No data are
      available comparing tetrofosmin and sestamibi imaging in the identification of
      reversible left ventricular (LV) dysfunction in the same patients. This study
      compared the results of tetrofosmin, thallium, and sestamibi single photon
      emission computed tomography at rest in detection of myocardial viability in
      patients with previous myocardial infarction. METHODS AND RESULTS: Seventeen
      patients with previous myocardial infarction who were undergoing coronary
      revascularization were studied. Echocardiography was performed at baseline and 3
      months after revascularization to evaluate recovery of LV function. The optimal
      threshold cutoffs to separate reversible from irreversible dysfunction, as
      determined by receiver operating characteristic analysis, were 55% of peak
      activity for both tetrofosmin and sestamibi and 60% for thallium. In all
      asynergic segments (n = 77) analyzed, tetrofosmin uptake correlated with both
      sestamibi (r = 0.90, P <.0001) and thallium (r = 0.85, P <.0001) activity. The
      sensitivity and specificity for reversible dysfunction were, respectively, 70%
      and 70% for tetrofosmin, 70% and 66% for sestamibi, and 60% and 68% for thallium
      imaging (all P = not significant). The areas under the receiver operating
      characteristic curves constructed for tetrofosmin, thallium, and sestamibi
      activity were 0.74 +/- 0.06 (mean +/- SD), 0.75 +/- 0.06, and 0.74 +/- 0.06,
      respectively (all P = not significant). Concordance for detecting myocardial
      viability between tetrofosmin and thallium imaging was found in 67 regions (87%)
      (kappa = 0.74), and concordance between tetrofosmin and sestamibi imaging was
      found in 69 regions (90%) (kappa = 0.79). CONCLUSIONS: The diagnostic performance
      of quantitative rest tetrofosmin single photon emission computed tomography in
      predicting functional recovery after revascularization is comparable to that of
      both thallium and sestamibi scintigraphy in patients with myocardial infarction
      and chronic LV dysfunction.

PMID- 11845129
TI  - Comparison of pulmonary uptake with transient cavity dilation after dipyridamole
      Tl-201 perfusion imaging.
AB  - BACKGROUND: Elevated lung-heart ratio (LHR) and transient ischemic dilation (TID)
      have been identified as markers of severe coronary artery disease after both
      exercise and pharmacologic stress testing. We have previously demonstrated a very
      weak correlation between elevated LHR and TID after exercise, which suggests that
      they reflect different pathophysiologic manifestations of coronary disease.
      Because the physiology of pharmacologic vasodilation with dipyridamole is
      significantly different than that of physical exercise, we undertook this study
      to evaluate the relationship between elevated LHR and TID after pharmacologic
      stress testing with dipyridamole. METHODS AND RESULTS: We identified 1129
      consecutive patients who underwent pharmacologic stress imaging with dipyridamole
      and thallium 201. LHR and a dilation index were calculated and compared with each
      other and with relevant clinical parameters. Echocardiographic parameters were
      also compared in a subset of 475 patients who had echocardiography within 2 weeks
      of pharmacologic stress testing. There was no significant correlation between
      elevated LHR and TID despite the fact that both were associated with more severe
      thallium stress and redistribution scores. Patients with elevated LHR were more
      likely to have a history of myocardial infarction and coronary artery bypass
      grafting and to have lower ejection fraction. Patients with TID were more likely
      to have a positive electrocardiographic response (15% vs 7%, P =.0003), which was
      not seen in patients with elevated LHR (11% vs 8%, P =.23). CONCLUSIONS: Although
      both elevated LHR and TID were associated with more severe coronary disease, they
      have no significant correlation. Patients with elevated LHR are more likely to
      have a history of myocardial infarction or coronary artery bypass grafting, a
      larger left ventricle, and lower ejection fraction. Our results support the
      hypothesis that TID is due to diffuse subendocardial hypoperfusion and represents
      a different pathophysiologic response to ischemia than elevated LHR.

PMID- 11845130
TI  - Improved coronary disease detection with quantitative attenuation-corrected Tl
      201 images.
AB  - BACKGROUND: The normal distribution of myocardial tracer activity is different in
      attenuation-corrected images compared with uncorrected images. We therefore
      postulated that quantitation of attenuation-corrected thallium 201 images with
      direct comparison to a database of healthy subjects could improve detection of
      coronary artery stenoses. METHODS AND RESULTS: In 49 patients with angiographic
      evidence of coronary artery disease and 69 patients with a less than 5%
      likelihood of coronary artery disease, tomographic Tl-201 myocardial imaging was
      performed by means of a triple-headed camera with fan-beam collimators and the
      images were processed with attenuation correction, with attenuation and Compton
      scatter correction, and without correction. Images were subjectively interpreted
      in a blinded manner. From the group of 69 patients with a low likelihood of
      coronary disease, scintigraphic data from the first 20 men and the first 20 women
      were used to generate normal reference ranges for each of the 3 image-processing
      methods. Data from the 49 patients with angiographic coronary disease and from
      the remaining 29 patients with a low likelihood of coronary disease were then
      analyzed quantitatively in comparison to the gender-matched normal databases.
      With visual interpretation, attenuation-corrected images yielded an improved
      detection rate compared with uncorrected images (79% vs 46%, P =.008) for 70% or
      greater left anterior descending coronary artery stenoses. Attenuation-corrected
      images also provided an improved normalcy rate for the right coronary artery
      territory (91% vs 75%, P =.006) and an improved normalcy rate when the images
      were analyzed overall by patient (88% vs 74%, P =.009). With quantitative
      analysis, attenuation correction yielded an improved detection rate for patients
      with a significant coronary artery stenosis compared with uncorrected images (90%
      vs 71%, P =.016). Defect extent was also increased by attenuation correction.
      Compared with attenuation correction alone, the addition of scatter correction
      yielded no incremental improvement in detection rate or normalcy rate.
      Attenuation-scatter correction did produce a nonsignificant trend toward
      detection of more of the total number of stenotic arteries compared with
      uncorrected images (60 vs 48 of 79 arteries). CONCLUSIONS: With the use of a
      triple-headed camera with fan-beam collimation, visual analysis of attenuation
      corrected Tl-201 images improved detection of left anterior descending coronary
      artery disease without loss of detection in other coronary territories.
      Furthermore, quantitative analysis of attenuation-corrected Tl-201 images
      improved the overall detection rate for coronary artery disease in patients
      without compromise of the normalcy rate.

PMID- 11845131
TI  - Reduced myocardial flow reserve in anatomically normal coronary arteries due to
      elevated baseline myocardial blood flow in men with old myocardial infarction.
AB  - BACKGROUND: Decreased myocardial flow reserve (MFR) in angiographically normal
      coronary arteries in patients with old myocardial infarction (OMI) has been
      reported. METHODS AND RESULTS: To clarify factors for the reduced MFR in OMI and
      to compare them with those in angina pectoris (AP), baseline myocardial blood
      flow (MBF) and MBF during dipyridamole administration were measured with nitrogen
      13 ammonia positron emission tomography, after which MFR was calculated for 13
      men with AP, 18 men with OMI, and 15 age-matched male control subjects. MFR was
      compared among the 3 groups in segments perfused by nonstenotic arteries.
      Baseline MBF in patients with OMI was significantly higher than that in patients
      with AP and control subjects. MBF during dipyridamole administration in patients
      with OMI was significantly lower than that in control subjects. MFR in patients
      with AP was 2.50 +/- 0.91 (P <.05 vs control subjects [3.47 +/- 1.25]), and that
      in patients with OMI was 1.83 +/- 0.61 (P <.01 vs control and AP groups).
      Ejection fraction (EF) in patients with OMI was significantly decreased compared
      with that in patients with AP. However, there was no significant difference in
      the mean score of the individual risk factors between patients with AP and those
      with OMI. In the pooled data with AP and OMI, baseline MBF and EF were
      significant for the reduced MFR. CONCLUSIONS: MFR and EF in patients with OMI
      were significantly decreased compared with those in patients with AP. Increased
      baseline MBF and decreased EF were significant factors for the reduced MFR in
      patients with AP and OMI.

PMID- 11845132
TI  - Consideration of perfusion reserve in viability assessment by myocardial Tl-201
      rest-redistribution SPECT: a quantitative study with dual-isotope SPECT.
AB  - BACKGROUND: To optimize the use of thallium 201 rest-redistribution study in Tl
      201/technetium 99m sestamibi dual-isotope single photon emission computed
      tomography (SPECT), the predictability of Tl-201 rest-redistribution for viable
      myocardium was examined according to the degree of perfusion reserve. METHODS AND
      RESULTS: Twenty patients with both unstable angina and left ventricular
      dysfunction were enrolled. Tl-201 rest-dipyridamole stress Tc-99m sestamibi gated
      SPECT/Tl-201 24-hour redistribution SPECT was performed before and 3 months after
      coronary artery bypass grafting. Through use of a 20-segment model, segmental
      stress perfusion, rest perfusion, and systolic thickening were quantified on
      gated SPECT by means of automatic quantitation software. Perfusion was expressed
      as the average percentage of maximal radioactivity uptake. To represent perfusion
      reserve, the perfusion difference score (PDS) was defined as rest perfusion minus
      stress perfusion. A low PDS indicated little or no inducible ischemia, and a high
      PDS indicated inducible ischemia. In dysfunctional myocardium, viability was
      defined by the improvement of thickening after coronary artery bypass grafting.
      The overall predictability of Tl-201 redistribution for viability was 0.709 of
      the area under the curve (AUC) in receiver operating characteristic analysis.
      With a cutoff of 7, predictability was significantly better in the low PDS group
      (AUC = 0.785) than in the high PDS group (AUC = 0.582). CONCLUSIONS: The
      predictability of Tl-201 rest-redistribution for viability differs according to
      perfusion reserve. It was more reliable for dysfunctional myocardium with
      persistent perfusion decrease. On the basis of the continuum hypothesis of
      chronic stunning and hibernation, we suggest that dysfunctional myocardium with
      persistent perfusion decrease should be assessed by Tl-201 redistribution SPECT.

PMID- 11845134
TI  - Atherosclerotic plaque morphology and coronary thrombi.

PMID- 11845136
TI  - Assessing diagnostic performance in nuclear cardiology.

PMID- 11845133
TI  - MIBG imaging.

PMID- 11845135
TI  - Pathophysiology of valvular heart disease: implications for nuclear imaging.

PMID- 11845137
TI  - Cardiac risk defined by stress myocardial perfusion imaging: Impact on physician
      decision making and cost savings.

PMID- 11845138
TI  - I-123 MIBG scintigraphy in idiopathic dilated cardiomyopathy: where next?

PMID- 11845139
TI  - Cardiac rhabdomyoma in an adult: an aspect of Tc-99m sestamibi myocardial
      perfusion.

PMID- 11845140
TI  - The value and practice of attenuation correction for myocardial perfusion SPECT
      imaging: a joint position statement from the American Society of Nuclear
      Cardiology and the Society of Nuclear Medicine.

PMID- 11845142
TI  - Accuracy of magnetic resonance imaging in determining the presence and size of
      recurrent rotator cuff tears.
AB  - We attempted to assess the accuracy of magnetic resonance imaging (MRI) in
      determining the size of recurrent cuff tears in correlation with size measured at
      surgery. Thirty-seven shoulders in 33 patients who had reoperation for a presumed
      failed rotator cuff repair were retrospectively evaluated. All patients had
      preoperative MRI, the results of which were read by a musculoskeletal radiologist
      to determine the presence of a tear and to estimate its size. All tears were
      measured intraoperatively in sagittal and coronal planes. Thirty-three shoulders
      had recurrent tears of the rotator cuff, and MRI correctly identified the
      presence of 30 of them. MRI correctly identified only 1 of the 4 patients without
      a recurrent tear of the cuff. The correlation coefficient for MRI accurately
      defining the size of cuff tears was 0.46. The sensitivity of MRI for the
      diagnosis of retear was 91%, and the specificity was 25%. MRI is accurate in
      diagnosing a recurrent full-thickness cuff tear in postsurgical shoulders.
      However, it is relatively inaccurate in correctly defining the size of the tear.
      MRI also has a tendency to overdiagnose cuff tears in postsurgical patients with
      continued pain and symptoms.

PMID- 11845141
TI  - Development of arthrosis following dislocation of the shoulder: a case-control
      study.
AB  - The goal of this study was to document whether an association exists between
      shoulder dislocation and the development of arthrosis and to quantify this
      association, if present. Patients with osteoarthrosis who had undergone hemi
      shoulder or total shoulder arthroplasty (TSA) were studied. Patients who had
      undergone total knee arthroplasty for arthrosis and who had no history of
      shoulder symptoms served as control subjects. All patients were asked if they had
      ever sustained a shoulder dislocation. Ninety-one TSA patients and 282 control
      subjects responded. The odds ratio for developing arthrosis after a shoulder
      dislocation was 19.3 (P =.000006). With the 5 patients who had shoulder surgery
      prior to TSA excluded, the odds ratio was 10.5 (P =.003). The risk of developing
      severe arthrosis of the shoulder is between 10 and 20 times greater for
      individuals who have had a dislocation of the shoulder.

PMID- 11845143
TI  - Prosthetic replacement in the treatment of osteoarthritis of the shoulder: early
      results of 268 cases.
AB  - Two hundred sixty-eight anatomically designed shoulder arthroplasties for primary
      osteoarthritis were reviewed at a mean follow-up of 30 months. The Constant score
      adjusted for age and sex was 38% preoperatively and 97% at follow-up. Good or
      excellent results were observed in 77% of patients, and 94% were satisfied or
      very satisfied. Mean active forward elevation was 145 degree postoperatively, and
      all clinical parameters improved. Glenoid radiolucent lines were present in 58%
      of cases and were associated with a less satisfactory objective result.
      Postoperative active forward elevation, strength, and Constant score were
      inversely related to a tear of the supraspinatus or fatty degeneration of the
      infraspinatus. Patients who underwent biceps tenodesis had better pain relief.
      Complications occurred in 8.6% of cases, and 4.9% of shoulders required
      reoperation. Good early results can be obtained with nonconstrained shoulder
      arthroplasty in primary osteoarthritis.

PMID- 11845144
TI  - Arthroscopic repair of medium to large full-thickness rotator cuff tears: outcome
      at 2- to 6-year follow-up.
AB  - Medium-term follow-up of arthroscopic rotator cuff repair was evaluated in 48
      consecutive arthroscopic repairs of medium to large rotator cuff tears. Mean
      rotator cuff tear size was 2.4 cm (range, 2-4 cm), mean age at surgery was 57.6
      years (range, 38-80 years), and mean follow-up was 39 months (range, 24-66
      months). Mean University of California at Los Angeles End-Result Scores were 17.2
      preoperatively and 33.7 postoperatively (P <.001). American Shoulder and Elbow
      Surgeons mean scores were 42.2 and 94.9, respectively. There were no
      complications requiring reoperation. There were 35 excellent, 11 good, 2 fair,
      and no poor results; however, 1 patient had clinical evidence of a failed repair.
      Forty-four of 45 patients (47/48 repairs) were satisfied with their results.

PMID- 11845145
TI  - Non-prosthetic management of grade IV osteochondral lesions of the glenohumeral
      joint.
AB  - Osteochondral lesions of the glenohumeral joint in early stages and in younger
      patients are an important problem and present a challenge during clinical
      decision making. Although prosthetic arthroplasty remains the gold standard for
      treatment in later stages of the disease, alternatives are desirable in the early
      stages and in young patients. The purposes of this study are to evaluate the
      results of arthroscopic debridement and capsular release in patients with grade
      IV osteochondral lesions of the glenohumeral joint and to determine the factors
      associated with their success. Sixty-one patients with grade IV osteochondral
      lesions of the glenohumeral articular surfaces were treated with arthroscopic
      debridement, with or without arthroscopic capsular release. Standardized data
      collection was performed at the initial office visit and at the time of final
      follow-up. Overall outcome was analyzed with regard to patients' self-assessment
      of pain, function, improvement, satisfaction, and duration of pain relief. Forty
      five of the patients had a minimum follow-up of 2 years. Time-to-event analysis
      was used to evaluate the duration of pain relief. The mean patient satisfaction
      score (0 = not satisfied; 10 = completely satisfied) improved from 0.67
      preoperatively to 6.28 at final follow-up (P <.0001), with 87% of patients
      indicating that they would have the surgery again. Although workers' compensation
      patients obtained inferior results, significant improvement in pain and function
      was obtained in 88% of all patients (P <.0001). Most patients noted the onset of
      pain relief within 5 weeks of surgery and obtained a duration of pain relief of
      28 months or greater (P <.05). The addition of concomitant procedures, such as
      acromioplasty, distal clavicle resection, labral debridement, or labral repair,
      did not have a negative impact on the functional results after arthroscopic
      debridement and capsular release. In well-selected patients with grade IV
      osteochondral lesions of the glenohumeral joint, significant improvements in pain
      relief and function follow arthroscopic debridement of the glenohumeral joint.
      Arthroscopic capsular release can be added in patients with a loss of passive
      arcs of shoulder motion. Osteochondral lesions greater than 2 cm(2) appear to be
      associated with return of pain and failure of this procedure.

PMID- 11845146
TI  - Reliability of 3 methods for assessing shoulder strength.
AB  - The reliability of tests for isometric strength of the shoulder joint in
      symptomatic subjects has yet to be established. For this purpose, interrater and
      intrarater agreement trials were undertaken to ascertain the reliability of
      manual muscle tests, a handheld dynamometer, and a spring-scale dynamometer for 5
      different shoulder movements in symptomatic subjects. Intraclass correlation
      coefficients were calculated from a random-effects model. All movements tested
      with the handheld dynamometer demonstrated excellent reliability for the
      interrater trial (rho = 0.79-0.92). Excellent reliability was also demonstrated
      for elevation, external rotation, and internal rotation for the intrarater trial
      (rho = 0.79-0.96). For the interrater trial, measurement of the lift-off maneuver
      with the handheld dynamometer was significantly more reliable than with manual
      muscle tests (P =.002). In summary, the handheld dynamometer was the most
      reliable and discriminatory means for assessing strength of the rotator cuff in
      symptomatic subjects.

PMID- 11845147
TI  - Interobserver and intraobserver reliability of the measurement of shoulder
      internal rotation by vertebral level.
AB  - Internal rotation is commonly measured as the vertebral level reached by the
      fully extended thumb. The purpose of this study was to evaluate interobserver and
      intraobserver reliability with the use of this method. Three male subjects were
      used for internal rotation measurement. Eleven orthopaedic surgeons and 2
      physical therapists served as examiners. Each subject had a radiographic marker
      placed at a random vertebral level, and the subject's extended thumb was placed
      at this marker. All examiners then independently measured internal rotation based
      on vertebral level. To assess intraobserver reliability, this process was
      repeated twice. After all measurements were completed, an anterior-posterior
      radiograph of each subject was obtained to define the vertebral level of the
      marker. This process was repeated 2 additional times with the marker and
      subject's thumb positioned at different levels than in the previous examination.
      Intraclass correlation coefficients were calculated to determine reliability.
      Results demonstrated poor interobserver reliability and reasonable intraobserver
      reliability. The mean clinical measurement deviated from the mean actual
      measurement by 1 vertebral level. Despite being the standard method in which
      shoulder internal rotation is measured, measurement of internal rotation by
      vertebral level is not readily reproducible between observers.

PMID- 11845148
TI  - Ligamentous restraints to anterior and posterior translation of the
      sternoclavicular joint.
AB  - This experiment was conducted to determine the primary ligamentous restraints to
      anterior and posterior translation of the sternoclavicular joint. Twenty-four
      unpaired cadaver specimens were mounted in a custom fixture. Anterior and
      posterior translations were measured under a sub-failure load in the intact
      specimen and again after transecting one randomly chosen ligament (anterior
      capsule, posterior capsule, interclavicular ligament, and costoclavicular
      ligament; n = 6 for each group). Cutting the posterior capsule resulted in
      significant increases in anterior translation and posterior translation. Cutting
      the anterior capsule produced significant increases in anterior translation.
      Cutting the costoclavicular and interclavicular ligaments had little effect on
      sternoclavicular joint translation. The posterior capsule is the most important
      restraint for anterior and posterior translation of the sternoclavicular joint.
      The anterior capsule is another important restraint for anterior translation. The
      costoclavicular and interclavicular ligaments have little effect on anterior or
      posterior translation of the sternoclavicular joint.

PMID- 11845149
TI  - Operative treatment of type C intercondylar fractures of the distal humerus:
      results after a mean follow-up of 2 years in a series of 18 patients.
AB  - We reviewed the results of internal fixation in a series of 18 patients (mean
      age, 44.4 years; SD, 19.1 years; range, 16-81 years) with type C intraarticular
      fractures of the distal humerus after a mean follow-up of 24.7 months (range, 10
      41 months; SD, 9.3 months). An excellent or good result was observed in 10
      patients (56%), according to the rating system of the Orthopaedic Trauma
      Association. All patients younger than 40 years (n = 8) had an excellent or good
      result, whereas those rates were found in only 2 of 10 patients older than 50
      years. Low range of elbow motion (extension-flexion) and, consequently, inferior
      postoperative score were also correlated to male sex, the triceps-splitting
      approach, and immobilization exceeding 3 weeks. When stability of the humeral
      columns is achieved and the articular platform is reconstructed, satisfactory
      results can be obtained, even in comminuted supracondylar fractures. However, age
      over 50 years, poor bone quality, and open fracture are correlated with increased
      risk for an inferior postoperative result. Early mobilization, when possible, and
      the use of an olecranon osteotomy are recommended.

PMID- 11845150
TI  - Functional anatomy of the lateral collateral ligament complex of the elbow:
      configuration of Y and its role.
AB  - A previous anatomic study has revealed that the lateral collateral ligament (LCL)
      complex of the elbow has a Y-shaped configuration, which consists of a superior,
      an anterior, and a posterior band. The LCL complex, including the annular
      ligament, functions as a 3-dimensional (3D) Y-shaped structure. On the basis of
      this concept, joint laxity after transection of the anterior band was studied in
      5 normal, fresh-frozen cadaver elbows with a 3D kinematic testing apparatus.
      Cutting the anterior band produced significant laxity to varus torque with a mean
      5.9 degree at 10 degree of elbow flexion and caused significant laxity to torque
      in external rotation with a mean 8.5 degree at 40 degree of flexion. No
      significant laxity was observed during application of valgus or internal
      rotational torque. Further transection of the posterior band resulted in gross
      instability with dislocation of the ulnohumeral joint. The laxity occurring after
      severance of the anterior band suggests that these fibers play a role in
      preservation of elbow stability against varus and external rotational torque.
      These results indicate that the LCL functions as a complex with a Y structure and
      not as an isolated linear ligament. A concept of conjoint point is hypothesized
      for the function of the LCL complex to restrain posterolateral rotatory
      instability.

PMID- 11845151
TI  - Single-strand reconstruction of the lateral ulnar collateral ligament restores
      varus and posterolateral rotatory stability of the elbow.
AB  - Because of a lack of biomechanical studies of lateral elbow ligament
      reconstruction in the literature, the initial stability afforded by 3 different
      techniques of lateral ulnar collateral ligament reconstruction was evaluated in 8
      cadaveric elbows. The arm was mounted in a testing apparatus, and passive flexion
      was performed with the arm in varus and valgus orientations. A pivot shift test
      was performed with the arm in the vertical orientation. An electromagnetic
      tracking device was used to quantify motion pathways. After intact testing, each
      specimen underwent sectioning of the radial collateral and lateral ulnar
      collateral ligaments from the lateral epicondyle. Reconstruction of the lateral
      ulnar collateral ligament was performed in a randomized sequence, consisting of
      proximal single-strand, distal single-strand, and double-strand tendon grafts.
      Division of the radial collateral and lateral ulnar collateral ligaments from the
      lateral epicondyle caused a significant decrease in rotational stability when the
      pivot shift test was being performed (P <.0001). Varus-valgus stability also
      decreased after transection of the radial collateral and lateral ulnar collateral
      ligaments (P <.0001). Reconstruction of the lateral ulnar collateral ligament
      restored elbow stability to that of the intact state. There was no significant
      difference in stability between the single- and double-strand repair techniques
      (P >.05). This study demonstrates that both single- and double-strand
      reconstructions restore varus and posterolateral elbow stability and may be
      considered appropriate reconstructive procedures in patients with symptomatic
      insufficiency of the lateral ligaments of the elbow.

PMID- 11845152
TI  - Single-strand ligament reconstruction of the medial collateral ligament restores
      valgus elbow stability.
AB  - The purpose of this study was to determine the contribution of the central
      portion of the anterior bundle of the medial collateral ligament (MCL) to elbow
      stability and to evaluate the effectiveness of a single-strand MCL reconstruction
      in restoring elbow stability. Testing of 11 fresh-frozen upper extremities was
      first performed on the intact elbow and then with the capsule, flexor-pronator
      muscle group, posterior bundle, anterior or posterior band, and central band cut
      sequentially. Next, a single-strand reconstruction of the MCL was performed. The
      elbow was moved passively through a full arc of flexion in both varus and valgus
      gravity-loaded positions. Ulnar movement with respect to the humerus was analyzed
      by means of an electromagnetic tracking system. Maximum varus-valgus laxity
      throughout the arc of supinated flexion and pronated flexion was 6.6 degree plus
      minus 2.4 degree and 7.4 degree plus minus 2.0 degree, respectively, for the
      intact specimen, 34.2 degree plus minus 5.6 degree and 37.7 degree plus minus
      11.8 degree for the specimen with all of the medial valgus elbow stabilizers cut,
      and 9.0 degree plus minus 2.5 degree and 10.5 degree plus minus 2.7 degree for
      the reconstructed specimen. Maximum varus-valgus laxity was not significantly
      different among any of the sectioning sequences until the central band was cut (P
      <.0001). There was no significant difference in maximum varus-valgus laxity
      between the intact and reconstructed elbows (P <.05). Our results demonstrate
      that the central band is an important valgus stabilizer of the elbow and that a
      simplified single-strand reconstruction is able to restore stability to the MCL
      deficient elbow.

PMID- 11845153
TI  - Glenoid osteophyte and rotator cuff tears: an anatomic study.
AB  - The purpose of this study was to determine the morphologic characteristics of the
      glenoid osteophyte and its relationship to rotator cuff tears. Eighty-six
      cadaveric shoulders were studied. After inspection of cuff pathology, the glenoid
      was examined with soft x-rays. Histologically, degenerative changes of the
      articular cartilage and the labrum were assessed. There were 30 shoulders with
      rotator cuff tears (35%). Two types of glenoid osteophyte were identified:
      angular and hooked. Both osteophytes were commonly observed in the anterior to
      inferior portions of the glenoid. The length of hooked osteophytes was
      significantly greater in shoulders with full-thickness tears (2.7 +/- 2.2 mm
      [mean plus minus SD]) than in those with other cuff conditions (P =.0058). The
      hooked osteophyte was more commonly observed in shoulders with full-thickness
      tears (43%) and associated with degenerative changes of the cartilage and labrum.
      We conclude that the hooked osteophyte of the glenoid is characteristic in
      shoulders with full-thickness tears of the rotator cuff.

PMID- 11845154
TI  - Scapulothoracic bursectomy for snapping scapula syndrome.
AB  - Seventeen patients (9 women and 8 men) were prospectively evaluated to determine
      the results of open scapulothoracic bursectomy in the treatment of unremitting,
      painful scapular crepitus (snapping scapula syndrome). The mean duration of
      symptoms was 2 years (range, 4 months-6 years). Twelve related an injury history,
      and 5 had insidious onset of symptoms. Three had previous superomedial angle
      resections without relief. The mean age at surgery was 35 years (19-53 years),
      and follow-up averaged 2.5 years (2-6 years). The surgical approach reflected the
      rhomboid major from the medial scapula, giving access to the scapulothoracic
      bursa between the serratus anterior muscle and the rib cage. Only 4 cases
      required primary superomedial angle bone resection and one a revision resection.
      Mean outcome scores significantly improved preoperatively to postoperatively:
      American Shoulder and Elbow Surgeons score: from 48 to 91; Simple Shoulder Test:
      from 6.2 to 10.1; and Visual Analog Score for Pain: from 6.1 to 1.0 (P <.05).
      Return to work and sports averaged 3.5 months. Open scapulothoracic bursectomy
      allowed evaluation and treatment of all areas of potential pathology. Symptomatic
      crepitus was relieved, and pain relief and functional improvement were
      consistently achieved.

PMID- 11845155
TI  - Persistent aseptic fistula after rotator cuff repair: fistuloscopic approach.

PMID- 11845156
TI  - Calcific tendinitis at the biceps brachii insertion of a child: a case report.

PMID- 11845157
TI  - Intermittent radial nerve palsy caused by a humeral osteochondroma: a case
      report.

PMID- 11845158
TI  - Intra-articular ganglion cyst (paralabral cyst) of the shoulder associated with
      recurrent anterior dislocation: a case report.

PMID- 11845159
TI  - Scapular body nonunion: a case report.

PMID- 11845160
TI  - Putting pathogens first.

PMID- 11845161
TI  - Drawing back the talent: Canada.

PMID- 11845162
TI  - A boost too far?

PMID- 11845163
TI  - Dangers of going underground.

PMID- 11845164
TI  - Biodefence boost leaves experts worried over laboratory safety.

PMID- 11845165
TI  - American Red Cross turns its back on stem-cell grant.

PMID- 11845166
TI  - Physicist's letters reveal clues to bitter wartime rift.

PMID- 11845168
TI  - Rockefeller head quits as scandal looms.

PMID- 11845169
TI  - Cloning agenda 'skewed' by media frenzy.

PMID- 11845171
TI  - Anger at US plan to drop physics experiment.

PMID- 11845175
TI  - Tightening the purse strings.

PMID- 11845174
TI  - The counting house.

PMID- 11845176
TI  - The impact-factors debate: the ISI's uses and limits.

PMID- 11845177
TI  - Statistics hide impact of non-English journals.

PMID- 11845179
TI  - Getting space camera back on track soon.

PMID- 11845178
TI  - Strange results mean it's worth checking ISI data.

PMID- 11845180
TI  - Habilitation not just alive in France, but growing.

PMID- 11845181
TI  - Narrow horizons in astrobiology.

PMID- 11845188
TI  - Innateness.

PMID- 11845190
TI  - Beyond the kitchen sink.

PMID- 11845189
TI  - Secret life of genes.

PMID- 11845192
TI  - Flow and fabric deep down.

PMID- 11845191
TI  - A case of dispersing chameleons.

PMID- 11845194
TI  - Snap judgements.

PMID- 11845195
TI  - Precision patterning.

PMID- 11845197
TI  - Stem cells that make stems.

PMID- 11845198
TI  - Rational imitation in preverbal infants.
AB  - Here we show that if an adult demonstrates a new way to execute a task to a group
      of infants aged 14 months, the children will use this action to achieve the same
      goal only if they consider it to be the most rational alternative. Our results
      indicate that imitation of goal-directed action by preverbal infants is a
      selective, interpretative process, rather than a simple re-enactment of the means
      used by a demonstrator, as was previously thought.

PMID- 11845199
TI  - Performance constraints in decathletes.
AB  - Physical performance by vertebrates is thought to be constrained by trade-offs
      between antagonistic pairs of ecologically relevant traits and between
      conflicting specialist and generalist phenotypes, but there is surprisingly
      little evidence to support this reasoning. Here we analyse the performance of
      world-class athletes in standardized decathlon events and find that it is subject
      to both types of trade-off, after correction has been made for differences
      between athletes in general ability across all 10 events. These trade-offs may
      have imposed important constraints on the evolution of physical performance in
      humans and other vertebrates.

PMID- 11845200
TI  - The emerging conceptual framework of evolutionary developmental biology.
AB  - Over the last twenty years, there has been rapid growth of a new approach to
      understanding the evolution of organismic form. This evolutionary developmental
      biology, or 'evo-devo', is focused on the developmental genetic machinery that
      lies behind embryological phenotypes, which were all that could be studied in the
      past. Are there any general concepts emerging from this new approach, and if so,
      how do they impact on the conceptual structure of traditional evolutionary
      biology? In providing answers to these questions, this review assesses whether
      evo-devo is merely filling in some missing details, or whether it will cause a
      large-scale change in our thinking about the evolutionary process.

PMID- 11845201
TI  - Crossover between classical and quantum shot noise in chaotic cavities.
AB  - The discreteness of charge in units of e led Schottky in 1918 to predict that the
      electrical current in a vacuum tube fluctuates even if all spurious noise sources
      are eliminated carefully. This phenomenon is now widely known as shot noise. In
      recent years, shot noise in mesoscopic conductors, where charge motion is quantum
      coherent over distances comparable to the system size, has been studied
      extensively. In those experiments, charge does not propagate as an isolated
      entity through free space, as for vacuum tubes, but is part of a degenerate and
      quantum-coherent Fermi sea of charges. It has been predicted that shot noise in
      mesoscopic conductors can disappear altogether when the system is tuned to a
      regime where electron motion becomes classically chaotic. Here we experimentally
      verify this prediction by using chaotic cavities where the time that electrons
      dwell inside can be tuned. Shot noise is present for large dwell times, where the
      electron motion through the cavity is 'smeared' by quantum scattering, and it
      disappears for short dwell times, when the motion becomes classically
      deterministic.

PMID- 11845202
TI  - Observation of stimulated emission by direct three-photon excitation.
AB  - Multiphoton processes, predicted theoretically in 1931, were for a long time
      considered to be mainly of academic interest. This view changed when it was shown
      that a two-photon absorption process could, because of a quadratic dependence of
      excitation on intensity, produce a spatially confined excitation useful for three
      dimensional data storage and imaging. Two-photon absorption has received
      considerable attention recently because of the development of highly efficient
      two-photon-sensitive materials, leading to numerous technological applications.
      These successes have created interest in exploring applications based on three
      photon excitations. For a three-photon process, a longer excitation wavelength
      such as those common in optical communications can be used. Also, the cubic
      dependence of the three-photon process on the input light intensity provides a
      stronger spatial confinement, so that a higher contrast in imaging can be
      obtained. Here we report the observation of a highly directional and up-converted
      stimulated emission as an amplified spontaneous emission, produced in an organic
      chromophore solution by a strong simultaneous three-photon absorption at 1.3
      microm. This achievement suggests opportunities for a three-photon process in
      frequency-upconversion lasing, short-pulse optical communications, and the
      emerging field of biophotonics.

PMID- 11845203
TI  - Why stainless steel corrodes.
AB  - Stainless steels are used in countless diverse applications for their corrosion
      resistance. Although they have extremely good general resistance, they are
      nevertheless susceptible to pitting corrosion. This localized dissolution of an
      oxide-covered metal in specific aggressive environments is one of the most common
      and catastrophic causes of failure of metallic structures. The pitting process
      has been described as random, sporadic and stochastic and the prediction of the
      time and location of events remains extremely difficult. Many contested models of
      pitting corrosion exist, but one undisputed aspect is that manganese sulphide
      inclusions play a critical role. Indeed, the vast majority of pitting events are
      found to occur at, or adjacent to, such second-phase particles. Chemical changes
      in and around sulphide inclusions have been postulated as a mechanism for pit
      initiation but such variations have never been measured. Here we use nanometre
      scale secondary ion mass spectroscopy to demonstrate a significant reduction in
      the Cr:Fe ratio of the steel matrix around MnS particles. These chromium-depleted
      zones are susceptible to high-rate dissolution that 'triggers' pitting. The
      implications of these results are that materials processing conditions control
      the likelihood of corrosion failures, and these data provide a basis for
      optimizing such conditions.

PMID- 11845204
TI  - Poleward heat transport by the atmospheric heat engine.
AB  - The atmospheric heat transport on Earth from the Equator to the poles is largely
      carried out by the mid-latitude storms. However, there is no satisfactory theory
      to describe this fundamental feature of the Earth's climate. Previous studies
      have characterized the poleward heat transport as a diffusion by eddies of
      specified horizontal length and velocity scales, but there is little agreement as
      to what those scales should be. Here we propose instead to regard the baroclinic
      zone--the zone of strong temperature gradients and active eddies--as a heat
      engine which generates eddy kinetic energy by transporting heat from a warmer to
      a colder region. This view leads to a new velocity scale, which we have tested
      along with previously proposed length and velocity scales, using numerical
      climate simulations in which the eddy properties have been varied by changing
      forcing and boundary conditions. The experiments show that the eddy velocity
      varies in accordance with the new scale, while the size of the eddies varies with
      the well-known Rhines beta-scale. Our results not only give new insight into
      atmospheric eddy heat transport, but also allow simple estimates of the
      intensities of mid-latitude storms, which have hitherto only been possible with
      expensive general circulation models.

PMID- 11845205
TI  - Mid-mantle deformation inferred from seismic anisotropy.
AB  - With time, convective processes in the Earth's mantle will tend to align
      crystals, grains and inclusions. This mantle fabric is detectable
      seismologically, as it produces an anisotropy in material properties--in
      particular, a directional dependence in seismic-wave velocity. This alignment is
      enhanced at the boundaries of the mantle where there are rapid changes in the
      direction and magnitude of mantle flow, and therefore most observations of
      anisotropy are confined to the uppermost mantle or lithosphere and the lowermost
      mantle analogue of the lithosphere, the D" region. Here we present evidence from
      shear-wave splitting measurements for mid-mantle anisotropy in the vicinity of
      the 660-km discontinuity, the boundary between the upper and lower mantle. Deep
      focus earthquakes in the Tonga-Kermadec and New Hebrides subduction zones
      recorded at Australian seismograph stations record some of the largest values of
      shear-wave splitting hitherto reported. The results suggest that, at least
      locally, there may exist a mid-mantle boundary layer, which could indicate the
      impediment of flow between the upper and lower mantle in this region.

PMID- 11845206
TI  - A basal troodontid from the Early Cretaceous of China.
AB  - Troodontid dinosaurs form one of the most avian-like dinosaur groups. Their
      phylogenetic position is hotly debated, and they have been allied with almost all
      principal coelurosaurian lineages. Here we report a basal troodontid dinosaur,
      Sinovenator changii gen. et sp. nov., from the lower Yixian Formation of China.
      This taxon has several features that are not found in more derived troodontids,
      but that occur in dromaeosaurids and avialans. The discovery of Sinovenator and
      the examination of character distributions along the maniraptoran lineage
      indicate that principal structural modifications toward avians were acquired in
      the early stages of maniraptoran evolution.

PMID- 11845207
TI  - Chameleon radiation by oceanic dispersal.
AB  - Historical biogeography is dominated by vicariance methods that search for a
      congruent pattern of fragmentation of ancestral distributions produced by shared
      Earth history. A focus of vicariant studies has been austral area relationships
      and the break-up of the supercontinent Gondwana. Chameleons are one of the few
      extant terrestrial vertebrates thought to have biogeographic patterns that are
      congruent with the Gondwanan break-up of Madagascar and Africa. Here we show,
      using molecular and morphological evidence for 52 chameleon taxa, support for a
      phylogeny and area cladogram that does not fit a simple vicariant history.
      Oceanic dispersal--not Gondwanan break-up--facilitated species radiation, and the
      most parsimonious biogeographic hypothesis supports a Madagascan origin for
      chameleons, with multiple 'out-of-Madagascar' dispersal events to Africa, the
      Seychelles, the Comoros archipelago, and possibly Reunion Island. Although
      dispersal is evident in other Indian Ocean terrestrial animal groups, our study
      finds substantial out-of-Madagascar species radiation, and further highlights the
      importance of oceanic dispersal as a potential precursor for speciation.

PMID- 11845208
TI  - Antagonistic coevolution between the sexes in a group of insects.
AB  - In coevolutionary 'arms races' between the sexes, the outcome of antagonistic
      interactions may remain at an evolutionary standstill. The advantage gained by
      one sex, with any evolutionary exaggeration of arms, is expected to be matched by
      analogous counteradaptations in the other sex. This fundamental coevolutionary
      process may thus be hidden from the evolutionist's eye, and no natural examples
      are known. We have studied the effects of male and female armament (clasping and
      anti-clasping morphologies) on the outcome of antagonistic mating interactions in
      15 species of water strider, using a combination of experimental and phylogenetic
      comparative methods. Here we present, by assessing the independent effects of
      both species-specific level of arms escalation and small imbalances in the
      amounts of arms between the sexes within species, the consequences of a sexual
      arms race. Evolutionary change in the balance of armament between males and
      females, but not in the species-specific level of escalation, has resulted in
      evolutionary change in the outcome of sexually antagonistic interactions such as
      mating rate.

PMID- 11845209
TI  - Context-enabled learning in the human visual system.
AB  - Training was found to improve the performance of humans on a variety of visual
      perceptual tasks. However, the ability to detect small changes in the contrast of
      simple visual stimuli could not be improved by repetition. Here we show that the
      performance of this basic task could be modified after the discrimination of the
      stimulus contrast was practised in the presence of similar laterally placed
      stimuli, suggesting a change in the local neuronal circuit involved in the task.
      On the basis of a combination of hebbian and anti-hebbian synaptic learning rules
      compatible with our results, we propose a mechanism of plasticity in the visual
      cortex that is enabled by a change in the context.

PMID- 11845210
TI  - Establishment of developmental precision and proportions in the early Drosophila
      embryo.
AB  - During embryonic development, orderly patterns of gene expression eventually
      assign each cell in the embryo its particular fate. For the anteroposterior axis
      of the Drosophila embryo, the first step in this process depends on a spatial
      gradient of the maternal morphogen Bicoid (Bcd). Positional information of this
      gradient is transmitted to downstream gap genes, each occupying a well defined
      spatial domain. We determined the precision of the initial process by comparing
      expression domains in different embryos. Here we show that the Bcd gradient
      displays a high embryo-to-embryo variability, but that this noise in the
      positional information is strongly decreased ('filtered') at the level of
      hunchback (hb) gene expression. In contrast to the Bcd gradient, the hb
      expression pattern already includes the information about the scale of the
      embryo. We show that genes known to interact directly with Hb are not responsible
      for its spatial precision, but that the maternal gene staufen may be crucial.

PMID- 11845211
TI  - Lateral relocation of auxin efflux regulator PIN3 mediates tropism in
      Arabidopsis.
AB  - Long-standing models propose that plant growth responses to light or gravity are
      mediated by asymmetric distribution of the phytohormone auxin. Physiological
      studies implicated a specific transport system that relocates auxin laterally,
      thereby effecting differential growth; however, neither the molecular components
      of this system nor the cellular mechanism of auxin redistribution on light or
      gravity perception have been identified. Here, we show that auxin accumulates
      asymmetrically during differential growth in an efflux-dependent manner.
      Mutations in the Arabidopsis gene PIN3, a regulator of auxin efflux, alter
      differential growth. PIN3 is expressed in gravity-sensing tissues, with PIN3
      protein accumulating predominantly at the lateral cell surface. PIN3 localizes to
      the plasma membrane and to vesicles that cycle in an actin-dependent manner. In
      the root columella, PIN3 is positioned symmetrically at the plasma membrane but
      rapidly relocalizes laterally on gravity stimulation. Our data indicate that PIN3
      is a component of the lateral auxin transport system regulating tropic growth. In
      addition, actin-dependent relocalization of PIN3 in response to gravity provides
      a mechanism for redirecting auxin flux to trigger asymmetric growth.

PMID- 11845212
TI  - The non-coding Air RNA is required for silencing autosomal imprinted genes.
AB  - In genomic imprinting, one of the two parental alleles of an autosomal gene is
      silenced epigenetically by a cis-acting mechanism. A bidirectional silencer for a
      400-kilobase region that contains three imprinted, maternally expressed protein
      coding genes (Igf2r/Slc22a2/Slc22a3) has been shown by targeted deletion to be
      located in a sequence of 3.7 kilobases, which also contains the promoter for the
      imprinted, paternally expressed non-coding Air RNA. Expression of Air is
      correlated with repression of all three genes on the paternal allele; however,
      Air RNA overlaps just one of these genes in an antisense orientation. Here we
      show, by inserting a polyadenylation signal that truncates 96% of the RNA
      transcript, that Air RNA is required for silencing. The truncated Air allele
      maintains imprinted expression and methylation of the Air promoter, but shows
      complete loss of silencing of the Igf2r/Slc22a2/Slc22a3 gene cluster on the
      paternal chromosome. Our results indicate that non-coding RNAs have an active
      role in genomic imprinting.

PMID- 11845213
TI  - Structural basis for antagonist-mediated recruitment of nuclear co-repressors by
      PPARalpha.
AB  - Repression of gene transcription by nuclear receptors is mediated by interactions
      with co-repressor proteins such as SMRT and N-CoR, which in turn recruit histone
      deacetylases to the chromatin. Aberrant interactions between nuclear receptors
      and co-repressors contribute towards acute promyelocytic leukaemia and thyroid
      hormone resistance syndrome. The binding of co-repressors to nuclear receptors
      occurs in the unliganded state, and can be stabilized by antagonists. Here we
      report the crystal structure of a ternary complex containing the peroxisome
      proliferator-activated receptor-alpha ligand-binding domain bound to the
      antagonist GW6471 and a SMRT co-repressor motif. In this structure, the co
      repressor motif adopts a three-turn alpha-helix that prevents the carboxy
      terminal activation helix (AF-2) of the receptor from assuming the active
      conformation. Binding of the co-repressor motif is further reinforced by the
      antagonist, which blocks the AF-2 helix from adopting the active position.
      Biochemical analyses and structure-based mutagenesis indicate that this mode of
      co-repressor binding is highly conserved across nuclear receptors.

PMID- 11845216
TI  - Risk factors for ovarian cancer: lesbian and heterosexual women.
AB  - PURPOSE/OBJECTIVES: To compare the distribution of risk factors for developing
      ovarian cancer in lesbian and heterosexual women. DESIGN: Secondary analysis of a
      retrospective medical record review. SETTING: Urban health clinic with special
      outreach to lesbians. SAMPLE: Typical participant (N = 1,019) was 42.9 years old
      and white (70%). Most were without health insurance, and 99% were poor (< $15,780
      annual income). The majority (58%, n = 586) described themselves as heterosexual;
      42% (n = 433) said they were lesbian. METHODS: Data were collected from medical
      records and analyzed using analysis of covariance and logistic regression
      techniques. MAIN RESEARCH VARIABLES: Ovarian cancer risk factors (parity,
      exogenous hormone use, smoking, body mass index [BMI], and tubal
      ligation/hysterectomy). FINDINGS: Lesbians had a higher BMI; heterosexual women
      had higher rates of current smoking and a higher incidence of the protective
      factors of pregnancy, children, miscarriages, abortions, and use of birth control
      pills. CONCLUSIONS: The results of this study indicate that lesbians may have an
      increased risk for developing ovarian cancer. A study designed specifically to
      explore the risk factors of lesbian and heterosexual women for developing ovarian
      cancer must be undertaken to confirm these findings. IMPLICATIONS FOR NURSING
      PRACTICE: Differences in risk levels may exist for lesbians; therefore,
      healthcare providers must become comfortable asking questions about sexual
      orientation and behavior.

PMID- 11845217
TI  - Effects of distraction using virtual reality glasses during lumbar punctures in
      adolescents with cancer.
AB  - PURPOSE/OBJECTIVES: To determine the effects of virtual reality (VR) glasses on
      adolescents with cancer undergoing lumbar punctures (LPs). DESIGN: Pilot study
      using an experimental, control group design. SETTING: In-hospital oncology
      clinic. SAMPLE: 30 adolescents with cancer (17 in the VR and 13 in the control
      group) undergoing frequent LPs. METHODS: Subjects were randomly assigned to
      groups. Both groups received standard intervention during the LP, but the
      experimental group also wore VR glasses and watched a video. Following the LP,
      both groups rated their pain using a visual analog scale (VAS) and were
      interviewed to evaluate their experience. MAIN RESEARCH VARIABLES: Pain,
      subjective evaluation of experience. FINDINGS: Although VAS pain scores were not
      statistically different between the two groups (p = 0.77), VAS scores tended to
      be lower in the VR group (median VAS of 7.0, range 0-48) than in the control
      group (median VAS of 9.0, range 0-59). 77% of subjects in the experimental group
      said the VR glasses helped to distract them from the LP. CONCLUSIONS: VR glasses
      are a feasible, age-appropriate, nonpharmacologic adjunct to conventional care in
      managing the pain associated with LPs in adolescents. IMPLICATIONS FOR PRACTICE:
      The clinical application of various age-appropriate distracters to reduce pain in
      adolescents undergoing painful procedures should be explored.

PMID- 11845219
TI  - The in vivo regulation of pulsatile insulin secretion.
AB  - The presence of oscillations in peripheral insulin concentrations has sparked a
      number of studies evaluating the impact of the insulin release pattern on the
      action of insulin on target organs. These have convincingly shown that equal
      amounts of insulin presented to target organs have improved action when delivered
      in a pulsatile manner. In addition, impaired (not absent) pulsatility of insulin
      secretion has been demonstrated in Type II (non-insulin-dependent) diabetes
      mellitus, suggesting a possible mechanism to explain impaired insulin action in
      Type II diabetes. Whereas the regulation of overall insulin secretion has been
      described in detail, the mechanisms by which this regulation affects the
      pulsatile insulin secretory pattern, and the relative and absolute contribution
      of changes in the characteristics of pulsatile insulin release have not been
      reviewed previously. This review will focus on the importance of the secretory
      bursts to overall insulin release, and on how insulin secretion is adjusted by
      changes in these secretory bursts. Detection and quantification of secretory
      bursts depend on methods, and the methodology involved in studies dealing with
      pulsatile insulin secretion is described. Finally, data suggest that impaired
      pulsatile insulin secretion is an early marker for beta-cell dysfunction in Type
      II diabetes, and the role of early detection of impaired pulsatility to predict
      diabetes or to examine mechanisms to cause beta-cell dysfunction is mentioned.

PMID- 11845220
TI  - Genetic linkage and association studies of Type I diabetes: challenges and
      rewards.
AB  - Family and twin studies have shown clearly that Type I (insulin-dependent)
      diabetes mellitus has a genetic basis. However, only within the past decade has
      it been possible to systematically attempt to identify the genes that increase
      susceptibility to this disorder using linkage and association analysis of genetic
      markers distributed across the genome. More than 20 putative diabetes
      predisposing genes have been localised in addition to HLA region susceptibility
      genes detected more than 25 years ago. Unfortunately, the effects of most
      diabetes-predisposing genes are weak, with the exception of HLA region
      susceptibility genes (which contribute about half of the genetic risk). The
      overall effects of diabetes-predisposing genes could be weak because the
      susceptibility gene occurs in only a small proportion of diabetic patients or the
      susceptibility gene (although it might be common) produces only a modest increase
      in risk, probably by acting in concert with other such genes to cause disease.
      The weak effects of these genes have made them difficult to locate, difficult to
      confirm in independent studies and difficult to isolate by genetic procedures.
      This paper summarizes the major challenges that have faced geneticists in mapping
      Type I diabetes genes, and reviews the progress achieved to date. The rewards of
      the genetic studies will be twofold: increased understanding of the causes of
      Type I diabetes, facilitating creation of preventative therapies, and enabling
      clinicians in the future to use genetic information to predict which children are
      predisposed to diabetes in order to target them for preventative therapies.

PMID- 11845221
TI  - Pregnancy and progression of diabetic nephropathy.
AB  - AIMS/HYPOTHESIS: Pregnancy could damage kidney function in diabetic nephropathy.
      We investigated the long-term impact of pregnancy on the progression of diabetic
      nephropathy. METHODS: Our observational follow-up study included all women
      patients with Type I (insulin-dependent) diabetes mellitus who developed diabetic
      nephropathy between 1970 and 1989 at Steno Diabetes Center (n = 93). Follow-up
      lasted 16 years (range 3-28) from the onset of diabetic nephropathy until death
      or the year 2000. A total of 26 women became pregnant after the onset of diabetic
      nephropathy (group A). The remaining 67 served as control subjects (group B). All
      patients received aggressive antihypertensive treatment (blood pressure goal <
      140/90 mmHg). RESULTS: The two groups were comparable at onset of diabetic
      nephropathy regarding blood pressure, albuminuria, s-cholesterol, smoking,
      retinopathy and s-creatinine (mean 79(SD 23) micromol/l). The slopes of 1/s
      creatinine (1000.l.micromol(-1).year(-1)) during the whole observation period
      were -0.39(0.40) compared with -0.41(0.70) (group A vs B-NS). The slopes of 1/s
      creatinine before and after pregnancy were similar. Decline in creatinine
      clearance (ml/min/yr) was 3.2 (3.4) compared with 3.2 (5.1) (group A vs B -NS).
      At the end of follow-up, 35 % (95 %-CI:17-53) of the pregnant women had died and
      19 % (7-39) had reached end stage renal disease compared to 34 % (23-45) and 24
      %(14-34) of the control subjects, respectively(NS). Group A and B had similar
      blood pressure levels during the whole observation period: 136(13)/83(7) vs 139
      (14)/85(7) mmHg (NS). CONCLUSION/INTERPRETATION: Pregnancy has no adverse long
      term impact on kidney function and survival in Type I diabetic patients with well
      preserved kidney function (normal serum creatinine) suffering from diabetic
      nephropathy.

PMID- 11845222
TI  - White blood-cell count and the risk of impaired fasting glucose or Type II
      diabetes in middle-aged Japanese men.
AB  - AIMS/HYPOTHESIS: To investigate the association between white blood-cell (WBC)
      count and the development of diabetes, independent of cigarette smoking. METHODS:
      We examined 2953 Japanese men who were office workers and between 35 and 59 years
      of age and who did not have impaired fasting glucose (IFG) (a fasting glucose
      concentration of 6.1-6.9 mmol/l), Type II (non-insulin-dependent) diabetes
      mellitus (a fasting glucose concentration of > or =7.0 mmol/l or more or receipt
      of hypoglycaemic medication), medication for hypertension, and a history of
      cardiovascular disease. Fasting glucose concentrations were measured at annual
      health examinations from May 1994 through May 2000. RESULTS: After controlling
      for potential predictors of diabetes, the relative risk for IFG or Type II
      diabetes mellitus compared with a WBC count of less than 5.3-10(9) cells/l was
      1.2 (95 %-CI, 0.6-2.3), 1.6 (CI, 0.8-3.1), and 2.5 (CI, 1.2-5.1) among non
      smokers (p for trend = 0.009): and 1.0 (CI, 0.4-2.5), 2.3 (CI, 1.0-5.1), and 3.1
      (CI, 1.4-7.1) among ex-smokers (p for trend = 0.001) with WBC counts of 5.3-6.1,
      6.2-7.2, and 7.3-10(9) cells/l or more, respectively. Among current smokers, the
      respective multivariate-adjusted relative risks for IFG or Type II diabetes
      mellitus were 1.1 (CI, 0.6-2.1), 1.4 (CI, 0.8-2.4), and 1.2 (CI, 0.7-2.1) (p for
      trend = 0.460). CONCLUSION/HYPOTHESIS: Although the selection of a rigorously
      normoglycaemic cohort might have had an influence on these observations, higher
      WBC counts seem to predict the development of IFG or Type II diabetes mellitus,
      primarily in non-smokers.

PMID- 11845223
TI  - Glucocorticoid induced insulin resistance impairs basal but not glucose entrained
      high-frequency insulin pulsatility in humans.
AB  - AIMS/HYPOTHESIS: Type II (non-insulin-dependent) diabetes mellitus is
      characterized by abnormal insulin secretion, which involves a disrupted basal and
      glucose-entrained insulin pulsatility, and by insulin resistance. The aim of this
      study was to examine the influence of glucocorticoid-mediated insulin resistance
      on the regularity of high frequency insulin pulsatility. METHODS: Eight healthy
      men (means +/- SD; age 24.4 +/- 0.5 years, BMI 23.2 +/- 0.7 kg/m2) were examined
      after prednisolone treatment (30 mg/day) or placebo for 6 days in a double-blind,
      placebo controlled, cross-over study with a 6-week washout period. Blood was
      collected every minute for 60 min during baseline and glucose-entrainment. Time
      series were assessed by spectral and autocorrelation analyses and a first-phase
      insulin secretion test was carried out. RESULTS: Prednisolone treatment led to
      insulin resistance as expected (HOMA-S; prednisolone vs placebo; 1.85 +/- 0.26 vs
      1.02 +/- 0.10; p < 0.01) with exaggerated first-phase insulin secretion (3016 +/-
      468 pmol/l vs 1688 +/- 207 pmol/l; p < 0.01), suggesting a stable disposition
      index. During baseline, normalized spectral power of serum insulin concentration
      time-series was reduced during prednisolone exposure compared with placebo (8.40
      +/- 0.95 vs 11.79 +/- 1.66; p < 0.05) indicating a disturbed high-frequency
      oscillatory insulin release. A similar trend was observed using autocorrelation
      analysis (0.23 +/- 0.04 vs 0.32 +/- 0.07; p = 0.12). During glucose entrainment
      no difference in normalized spectral power or in the autocorrelation coefficient
      between prednisolone and placebo (p > 0.1) was observed.
      CONCLUSION/INTERPRETATION: Six days of prednisolone treatment resulted in a
      pertubed high-frequency insulin release in the fasting state whereas the ability
      of glucose to entrain insulin secretion was preserved. This indicates a mechanism
      of pertubed glucose-insulin feedback mechanism which causes irregular oscillatory
      insulin release.

PMID- 11845224
TI  - 5-Aminoimidazole-4-carboxamide ribonucleoside treatment improves glucose
      homeostasis in insulin-resistant diabetic (ob/ob) mice.
AB  - AIMS/HYPOTHESIS: The 5'AMP-activated protein kinase is an important mediator of
      muscle contraction-induced glucose transport and a target for pharmacological
      treatment of Type II (non-insulin-dependent) diabetes mellitus. The 5'AMP
      activated protein kinase can be activated by 5-aminoimidazole-4-carboxamide
      ribonucleoside. We hypothesised that 5-aminoimidazole-4-carboxamide
      ribonucleoside treatment could restore glucose homeostasis in ob/ob mice.
      METHODS: Lean and ob/ob mice were given 5-aminoimidazole-4-carboxamide
      ribonucleoside (1 mg.g body wt(-1).day(-1) s.c) or 0.9 % NaCl (vehicle) for 1-7
      days. RESULTS: Short-term 5-aminoimidazole-4-carboxamide ribonucleoside treatment
      normalised glucose concentrations in ob/ob mice within 1 h, with effects
      persisting over 4 h. After 1 week of daily injections, 5-aminoimidazole-4
      carboxamide ribonucleoside treatment corrected hyperglycaemia, improved glucose
      tolerance, and increased GLUT4 and hexokinase II protein expression in skeletal
      muscle, but had deleterious effects on plasma non-esterified fatty acids and
      triglycerides. Treatment with 5-aminoimidazole-4-carboxamide ribonucleoside
      increased liver glycogen in fasted and fed ob/ob mice and muscle glycogen in
      fasted, but not fed ob/ob and lean mice. Defects in insulin-stimulated
      phosphatidylinositol 3-kinase and glucose transport in skeletal muscle from ob/ob
      mice were not corrected by 5-aminoimidazole-4-carboxamide ribonucleoside
      treatment. While ex vivo insulin-stimulated glucose transport was reduced in
      isolated muscle from ob/ob mice, the 5-aminoimidazole-4-carboxamide
      ribonucleoside stimulated response was normal. CONCLUSION/INTERPRETATION: The 5
      aminoimidazole-4-carboxamide ribonucleoside mediated improvements in glucose
      homeostasis in ob/ob mice can be explained by effects in skeletal muscle and
      liver. Due to the apparently deleterious effects of 5-aminoimidazole-4
      carboxamide ribonucleoside on the blood lipid profile, strategies to develop
      tissue-specific and pathway-specific activators of 5'AMP-activated protein kinase
      should be considered in order to improve glucose homeostasis.

PMID- 11845225
TI  - Progression to insulin-requiring diabetes in seronegative prediabetic subjects:
      the role of two HLA-DQ high-risk haplotypes.
AB  - AIMS/HYPOTHESIS: Most Caucasians with Type I (insulin-dependent) diabetes
      mellitus develop an autoimmune form of diabetes known as Type IA diabetes, based
      on the presence of humoral responses to islet autoantigens. Alleles at the HLA
      locus account for the strongest susceptibility to this form of diabetes, which
      requires insulin therapy. Because a number of patients who develop insulin
      requiring diabetes are islet autoantibody negative, the HLA class II haplotypes,
      DQA1*0501-DQB1*0201 and DQA1*0301-DQB1*0302, were evaluated to assess whether
      they are an independent risk factor for progression to insulin requirement in
      first-degree relatives of Type I diabetic patients. METHODS: Both HLA-DQ
      genotyping and islet cell autoantibody assessment (insulin, GAD65, IA-2
      autoantibodies and cytoplasmic islet cell antibodies) were evaluated
      prospectively in 74 relatives of Type I diabetic patients who developed diabetes
      treated with insulin (prediabetics) and in 426 control subjects who did not
      develop insulin-requiring diabetes. Based on the presence of DQA1*0501-DQB1*0201
      and/or DQA1*0301-DQB1*0302, the number of HLA-DQ high-risk haplotypes was
      assigned as 0, 1 or 2. RESULTS: A higher prevalence of 2 HLA-DQ high-risk
      haplotypes was present in seronegative prediabetic subjects as compared to non
      diabetic autoantibody negative first-degree relatives (33.3 % vs 10.1 %
      respectively; p < 0.05). Moreover, in seronegative relatives who developed
      insulin-requiring diabetes, the presence of 2 HLA-DQ high-risk haplotypes
      conferred an increased cumulative risk of developing insulin requirement of 27 %
      at 12.5 years of follow-up, compared to a risk of 6 % for non-diabetic relatives
      who were antibody-negative and had 0 or 1 HLA-DQ high-risk haplotypes (Log rank p
      = 0.01). CONCLUSION/INTERPRETATION: These data provide evidence for a phenotype,
      which is associated with the absence of conventional islet autoantibodies at
      initial screening, while usually remaining seronegative, and the presence of 2
      HLA-DQ high-risk haplotypes with progression to clinical Type I diabetes after a
      prolonged follow-up. Given the fact that in humans the highest risk-conferring
      locus associated and linked to the disease is the HLA cluster, and that HLA-DQ
      molecules play a key role in the development of autoimmune diabetes, our
      observations imply that as yet unidentified immunologic abnormalities could well
      exist in seronegative relatives at risk of developing clinical diabetes and
      carrying 2 HLA-DQ high-risk haplotypes.

PMID- 11845226
TI  - Successful [correction of Succesful] transplantation of human islets in
      recipients bearing a kidney graft.
AB  - AIMS/HYPOTHESIS: Islet transplantation is a minimally invasive approach to curing
      Type I (insulin-dependent) diabetes mellitus. Success has recently been reported
      in patients receiving solitary islet transplants but the outcome in patients
      receiving islets together with, or after, kidney transplants has been limited and
      unpredictable. METHODS: Here we report successful islet transplantation in a
      cohort of 15 patients with Type I diabetes who were followed for at least 1 year
      after islet transplantation, after having already received kidney allografts
      because of end-stage nephropathy. RESULTS: C-peptide after transplantation was
      higher than 0.17 nmol/l in all 15 recipients, reflecting the absence of primary
      non-function. Insulin requirement was reduced by over 50 % in all but one
      patient, and insulin independence was achieved in 10 (66 %) recipients, five of
      whom now have stable, prolonged insulin independence, well controlled fasting
      glycaemia, a substantial first-phase and normal second-phase response to glucose,
      normal insulin sensitivity (HOMA analyses) and HbA1 c of under 6.2 % (33, 26, 18,
      13 and 12 months after transplantation respectively). Of importance for patient
      management, an assessment of fasting blood glucose and proinsulin values
      following overnight withdrawal of insulin administration one month after
      transplantation was a potent predictor of insulin independence, and could be used
      to decide patients who should have further islet preparations.
      CONCLUSION/INTERPRETATION: These findings support the use of islet
      transplantation as a cure for Type I diabetes in patients with severe
      complications.

PMID- 11845227
TI  - Reduced beta-cell mass and expression of oxidative stress-related DNA damage in
      the islet of Japanese Type II diabetic patients.
AB  - AIMS/HYPOTHESIS: We examined the pancreatic islet lesions in Japanese patients
      with Type II diabetes mellitus to determine if the damage was related to
      oxidative stress. METHODS: Morphometric analyses were performed on immunostained
      sections of the tail portion of the pancreas from 14 diabetic and 15 non-diabetic
      patients. Amyloid deposition and oxidative stress-induced tissue damage were
      evaluated by Congo-red staining and immunostaining. Resistance to oxidative
      stress was assessed from immunostaining results for Cu, Zn-superoxide dismutase
      (SOD). Expression of (pro)insulin mRNA was assessed by in situ hybridisation.
      RESULTS: The pancreas from diabetic patients had amyloid deposition in about 15 %
      of the islets, intensified reactions of 8-OHdG and HNE, as well as reduced
      expression of SOD. Islet volume density of beta cells and total beta-cell mass in
      the pancreas from diabetic patients were reduced by 22 % (p < 0.001) and 30 % (p
      < 0.05). Islet volume density and total mass of (pro)insulin mRNA-positive cells
      were similarly reduced in diabetic patients by 22 % (p < 0.001) and 39 % (p <
      0.05), respectively. Islet volume density of A cells was increased by 20 % (p <
      0.001) but total mass did not change. There were no changes in volume densities
      of islet, D and PP cells. Reduced beta-cell volume density correlated with
      increased positive staining of 8-OHdG. CONCLUSION/INTERPRETATION: Japanese Type
      II diabetic patients show a reduction of beta-cell mass and evidence of increased
      oxidative stress-related tissue damage that is correlated with the extent of the
      beta-cell lesions.

PMID- 11845228
TI  - The pancreatic beta-cell-specific transcription factor Pax-4 inhibits glucagon
      gene expression through Pax-6.
AB  - AIMS/HYPOTHESIS: The paired-homeobox genes pax-4 and pax-6 are crucial for islet
      development; whereas the null mutation of pax-6 results in the nearly absence of
      glucagon-producing alpha cells, pax-4 homozygous mutant mice lack insulin and
      somatostatin-producing beta and delta cells but contain an increased number of
      alpha cells suggesting that alpha cells could develop by a default mechanism.
      METHODS: To investigate whether beta-cell specific factors act negatively on
      glucagon gene transcription, we ectopically expressed pax-4 in glucagon producing
      InR1G9 cells; Pax-4 inhibited basal transcription of the glucagon gene promoter
      by 60%. To assess the mechanism of this inhibition, we cotransfected the non
      islet cell line BHK-21 with Pax-4 and various transcription factors present in
      alpha cells. RESULTS: In addition to a general repressor activity on basal
      glucagon gene promoter activity of 30-50%, a specific 90% inhibition of Pax-6
      mediated transactivation was observed. In contrast, Pax-4 had no effect on Cdx
      2/3 or HNF3alpha mediated transcriptional activation. Pax-4 showed similar
      affinity to the Pax-6 binding sites on the glucagon gene promoter compared to Pax
      6, but varying with KCl concentrations. CONCLUSION/INTERPRETATION: Pax-4 impairs
      glucagon gene transcription specifically through inhibition of Pax-6 mediated
      transactivation. Transcriptional inhibition seems to be mediated by direct DNA
      binding competition with Pax-6 and potentially additional mechanisms such as
      protein-protein interactions and a general repressor activity of Pax-4. Glucagon
      gene expression in alpha cells could thus result from both the presence of islet
      cell specific transcription factors and the absence of Pax-4.

PMID- 11845229
TI  - Impaired intellectual development in children with Type I diabetes: association
      with HbA(1c), age at diagnosis and sex.
AB  - AIMS/HYPOTHESIS: Good metabolic control in diabetic children is already crucial
      before puberty to prevent diabetic complications later in life. However, tight
      metabolic control could increase the risk of severe hypoglycaemia, which might be
      responsible for impaired intellectual performance later in life. The purpose of
      this prospective longitudinal study was to evaluate the relevance of long-term
      metabolic control and hypoglycaemia possibly affecting the intellectual
      development of young children with Type I (insulin-dependent) diabetes mellitus.
      METHODS: The intellectual development in 64 diabetic children between the ages of
      7 and 16 years was assessed at least four times using the German version of the
      Hamburg Wechsler intelligence scale for preschool children, Children-Revised and
      by the "Adaptives Intelligenz Diagnostikum" (Adaptive Intelligence Diagnosticum).
      Data were analysed longitudinally compared with a control group. RESULTS: A
      significant decline in performance by age 7 and in verbal intelligence quotient
      between age 7 and 16 years was observed in diabetic boys diagnosed before the age
      of 6 but not in those diagnosed later and not in diabetic girls. The
      deterioration of intellectual performance in boys diagnosed at a very young age
      was not associated with the occurrence of severe hypoglycaemic episodes but was
      correlated with the degree of metabolic deterioration at diagnosis and with high
      long-term average of glycated haemoglobin. CONCLUSION/INTERPRETATION: Our study
      in diabetic children shows that the male sex, diagnosis at a young age, metabolic
      condition at diagnosis and long-term metabolic control, rather than experienced
      hypoglycaemic attacks are risk factors for intellectual development.

PMID- 11845230
TI  - Orosomucoid in urine predicts cardiovascular and over-all mortality in patients
      with Type II diabetes.
AB  - AIMS/HYPOTHESIS: Urinary orosomucoid excretion rate is increased in a substantial
      proportion of patients with Type II (non-insulin-dependent) diabetes mellitus and
      normal urinary albumin excretion rate. The aim of this study was to determine
      whether increased urinary orosomucoid excretion rate is predictive of increased
      mortality in patients with Type II diabetes. METHODS: In a cohort study including
      430 patients with Type II diabetes, baseline urinary samples were analysed for
      orosomucoid and albumin. Mean follow-up was 2.4 years. RESULTS: We found that 188
      (44 %) patients had normal and 242 (56 %) patients had increased urinary
      orosomucoid excretion rates. During the study period 41 patients died; out of
      these 23 patients died of cardiovascular diseases. Odds ratio for all-cause
      mortality was 2.50 (95 % CI 1.00-6.22) and odds ratio for cardiovascular
      mortality was 9.81 (1.31-73.6) having increased urinary orosomucoid excretion
      rate at baseline (odds ratios adjusted for age, sex, duration of diabetes,
      cardiovascular diseases, weight, medication, HbA1 c, plasma creatinine and
      urinary albumin excretion rate). Urinary albumin excretion rate was an
      independent predictor of all-cause mortality when urinary orosomucoid excretion
      rate was not included in the analysis. Subgroup analysis revealed that 39 % of
      the patients with normal urinary albumin excretion rate (n = 251) had increased
      urinary orosomucoid excretion rates and that these patients had a higher
      cardiovascular mortality (p = 0.007) than patients with normal urinary albumin
      excretion rate and normal urinary orosomucoid excretion rates.
      CONCLUSION/INTERPRETATION: We found that urinary orosomucoid excretion rate
      predicted all-cause and cardiovascular mortality in patients with Type II
      diabetes independently from other risk factors.

PMID- 11845231
TI  - Retinal photoreceptors of Syrian hamsters undergo oxidative stress during
      streptozotocin-induced diabetes.
AB  - AIMS/HYPOTHESIS: The aim of this study was to verify whether retinal
      photoreceptors, like other tissues, are subject to oxidative stress during
      diabetes. METHODS: Oxidative stress was monitored by the oxidation of preloaded
      dehydrorhodamine 123 into fluorescent rhodamine 123, during a period of intense
      illumination of isolated rod retinal receptor cells. These were obtained from 22
      Syrian hamsters injected with streptozotocin (50 mg/kg body weight.,
      intraperitoneal route) 90 days before the study began. Eleven hamsters were
      treated daily with melatonin (0.4 mg/kg body wt., per os), an antioxidant
      synthesized within photoreceptors. Isolated photoreceptors were bathed on the
      stage of a Leitz Orthoplan microscope, where the fluorescent lamp also served as
      the light stimulus (485 nm). Fluorescence irradiance was measured by photometry
      and stored in a personal computer for further analysis. RESULTS: The light
      induced oxidant production greatly decreased and was also delayed in the
      streptozotocin-injected hamsters compared with the control hamsters matched for
      age. Similar effects were obtained in control photoreceptors after 40 min
      incubation with 2-2'-azobis (2-amidinopropane) dihydrochloride, a potent
      lipoperoxidation inducer. The effect of melatonin was to partially restore the
      light-induced fluorescence response. CONCLUSION/INTERPRETATION: The depression of
      the light-induced oxidative response in diabetic photoreceptors could be ascribed
      to a hyperglycaemia-induced background of oxidative stress whereby the light
      oxidizable substrate is actually lowered. Melatonin induces a larger fluorescence
      response during illumination, probably as a consequence of its antioxidant effect
      during diabetes, which would provide more oxidizable lipids.

PMID- 11845233
TI  - Complete mutation scan of the human Fas ligand gene: linkage studies in Type I
      diabetes mellitus families.
AB  - AIMS/HYPOTHESIS: Type I (insulin-dependent) diabetes mellitus is the result of a
      T-cell regulated selective destruction of pancreatic beta cells. There is
      evidence that the apoptosis inducing T-cell effector, Fas ligand (FasL) could be
      involved in the pathogenesis of Type I diabetes, probably because FasL-mediated
      apoptosis is important in maintaining peripheral self-tolerance and in down
      regulating an immune response. We therefore evaluated the human FasL gene FASL on
      chromosome 1q23 as a candidate susceptibility gene for Type I diabetes. METHODS:
      The entire FASL (promoter, exons 1-4 and 3'UTR) was scanned for polymorphisms
      using single strand conformational polymorphism-heteroduplex analysis and direct
      sequencing. RESULTS: We identified two novel polymorphisms, a g-C843T and a g
      A475T, in a negative regulatory region of the promoter. A Danish Type I diabetes
      family collection of 1143 subjects comprising 257 families (420 affected and 252
      unaffected offspring) was typed for the g-C843T polymorphism and for a FASL
      microsatellite. Haplotypes were established and data were analysed using the
      extended transmission disequilibrium test. CONCLUSION/INTERPRETATION: We found no
      overall evidence for linkage in the presence of association of the FASL
      polymorphism to Type I diabetes and conclude that FASL does not contribute to the
      genetic susceptibility to Type I diabetes.

PMID- 11845232
TI  - Role of 12-lipoxygenase and oxidant stress in hyperglycaemia-induced acceleration
      of atherosclerosis in a diabetic pig model.
AB  - AIMS/HYPOTHESIS: We previously showed that vascular smooth muscle cells and
      endothelial cells cultured under high glucose conditions produced more 12(S)
      hydroxyeicosatetraenoic acid (12-HETE), the 12-lipoxygenase (12-LO) product of
      arachidonate metabolism, relative to normal glucose. Because the lipoxygenase
      (LO) pathway has been associated with oxidant stress and the pathogenesis of
      atherosclerosis, we now examined 12-LO activation in vivo in a pig model of
      diabetes-induced accelerated atherosclerosis which displays human
      characteristics. METHODS: The animal model was developed in pigs who were fed a
      normal or high fat diet and given streptozotocin injections to produce
      normolipemic-normoglycaemic (NLNG), normolipemic-hyperglycaemic (NLHG),
      hyperlipemic-normoglycaemic (HLNG) and hyperlipemic-hyperglycaemic (HLHG) pigs.
      Tissue samples were obtained from key arterial beds to examine 12-LO expression
      at 20 weeks after the pigs began their diet. RESULTS: All HG pigs maintained
      threefold higher serum glucose concentrations. The HL groups developed
      atherosclerosis but diabetic HLHG pigs showed markedly accelerated
      atherosclerosis (twofold) relative to non-diabetic HLNG pigs. Immunostaining
      showed progressive increases in 12-LO in arteries in the order NLNG, NLHG, HLNG
      and HLHG. Leukocyte-type 12-LO protein (immuno-blotting) as well as mRNA
      expression (by competitive PCR) in abdominal and coronary arteries were
      significantly greater in HLHG pigs than in all the other three groups.
      Furthermore, increased oxidant stress was observed in monocytes from NLHG and
      HLNG pigs, and greatly potentiated in HLHG pigs. CONCLUSIONS/INTERPRETATION:
      These results are consistent with the hypothesis that 12-LO activation plays a
      key role in accelerated atherosclerosis due to diabetes and hyperlipemia.

PMID- 11845234
TI  - DNA demethylation modulates mouse leptin promoter activity during the
      differentiation of 3T3-L1 cells.
AB  - AIMS/HYPOTHESIS: The mouse leptin gene, a major hormonal regulator of appetite
      and fat cell mass, expresses during the differentiation of 3T3-L1 preadipocytes
      to adipocytes. To determine if DNA methylation is involved in regulating the
      expression of the leptin gene, we examined the methylation status and methylation
      sensitive transcription factors during 3T3-L1 differentiation. METHODS: DNase I
      footprinting, electrophoretic mobility-shift assays, and a Southwestern analysis
      were carried out using nuclear extracts from preadipocytes and adipocytes.
      Promoter activity was measured by luciferase assays. The CpG methylation pattern
      was determined. RESULTS: Transient transfection of reporter constructs with the
      leptin promoter showed that preadipocytes that do not transcribe the leptin gene
      show enough transactivation, suggesting the presence of an additional regulatory
      mechanism. We identified eight CpG sites in the promoter up to nt -161, all of
      which were highly methylated ( > 92 %) in preadipocytes. Seven of these sites
      showed a varying degree of demethylation during differentiation, while the site
      at nt -54 remained methylated. In electrophoretic mobility-shift assays, DNA
      fragments from nt -115 to nt -70 generated a methylation-sensitive band with
      nuclear extracts from preadipocytes when the CpG sites were methylated.
      Southwestern analysis identified a 52 kMr protein that binds strongly to the
      methylated probes. Promoter activity was reduced by methylation of the CpG sites
      up to nt -115, but not up to nt -70. CONCLUSION/INTERPRETATION: These results
      suggest that methylation of specific CpG sites between nt -115 and nt -70 and a
      methylation-sensitive protein could contribute to leptin gene expression during
      adipocyte differentiation in 3T3-L1 cells.

PMID- 11845235
TI  - Subclinical inflammation in newly detected Type II diabetes and impaired glucose
      tolerance.

PMID- 11845236
TI  - Reduced lipolysis as possible cause for greater weight gain in subjects with the
      Pro12Ala polymorphism in PPARgamma2?

PMID- 11845237
TI  - A novel hepatocyte nuclear factor-1beta (MODY-5) gene mutation in an Italian
      family with renal dysfunctions and early-onset diabetes.

PMID- 11845238
TI  - Identification of a gain-of-function mutation in the HNF-1beta gene in a Japanese
      family with MODY.

PMID- 11845239
TI  - --to: Charlton R, Smith G, Day A (2001) Munchausen's syndrome manifesting as
      factitious hypoglycaemia. Diabetologia 44: 784-785.

PMID- 11845240
TI  - --to: T. Skoog et al. (2001) Tumour necrosis factor-alpha(TNF-alpha)
      polymorphisms -857C/A and -863C/A are associated with TNF-alpha secretion from
      human adipose tissue. Diabetologia 44: 654-655.

PMID- 11845241
TI  - The brainstem burst generator for saccadic eye movements: a modern synthesis.
AB  - In the 16 years since we last summarized the behavior of the premotor elements
      that control saccades, research has revealed shortcomings in previous
      formulations of the control mechanisms of the brainstem saccadic burst generator.
      Specifically, complexities in the eye movement plant, a more detailed knowledge
      of the behaviors of certain bursting neurons, and previously undiscovered
      anatomical connections have broadened our knowledge but have generated new
      questions that require rethinking previous concepts. Perhaps the most crucial
      revelations/insights have come from studies that have implicated the superior
      colliculus and the midline cerebellum as crucial elements of the burst generator.
      In summarizing these recent findings here, we have been led to conclude that the
      superior colliculus issues the saccadic command and receives feedback from the
      brainstem burst generators, but the feedback does not control saccade size. In
      addition, the midline cerebellum also contains a feedback path, but only as part
      of a more generalized circuit that serves multiple functions.

PMID- 11845242
TI  - Restoration of visual orienting into a cortically blind hemifield by reversible
      deactivation of posterior parietal cortex or the superior colliculus.
AB  - A contralateral hemineglect of the visual field can be induced by unilateral
      cooling deactivation of posterior middle suprasylvian (pMS) sulcal cortex of the
      posterior parietal region, and this neglect can be reversed by additional cooling
      deactivation of pMS cortex in the opposite hemisphere. The purpose of the present
      study was to test whether an enduring hemianopia induced by removal of all
      contiguous visual cortical areas of one hemisphere could be reversed by local
      cooling of pMS cortex in the opposite hemisphere. Two cats sustained large
      unilateral ablations of the contiguous visual areas, and cooling loops were
      placed in the pMS sulcus, and in contact with adjacent area 7 or posterior
      ectosylvian (PE) cortex of the opposite hemisphere. In both instances cooling of
      pMS cortex, but neither area 7 nor PE, restored a virtually normal level of
      orienting performance to stimuli presented anywhere in the previously hemianopic
      field. The reversal was highly sensitive to the extent of cooling deactivation.
      In a third cat, cooling deactivation of the superficial layers of the
      contralateral superior colliculus also restored orienting performance to a
      cortical ablation-induced hemianopia. This reversal was graded from center-to
      periphery in a temperature-dependent manner. Neither the cortical ablation nor
      any of the cooling deactivations had any impact on an auditory detection and
      orienting task. The deactivations were localized and confirmed by reduced uptake
      of radiolabeled 2-deoxyglucose to be limited to the immediate vicinity of each
      cooling loop. The results are discussed in terms of excitation and disinhibition
      of visual circuits.

PMID- 11845243
TI  - Activation of the supplementary motor area and of attentional networks during
      temporal processing.
AB  - This paper first provides a survey of the expanding brain imaging literature in
      the field of time processing, showing that particular task features (discrete vs
      rhythmic, perceptual vs motor) do not significantly affect the basic pattern of
      activation observed. Next, positron emission tomography (PET) data obtained in a
      timing task (temporal reproduction) with two distinct duration ranges (2.2--3.2
      and 9--13 s) are reported. The stimuli consisted of vibrations applied to the
      subject's right middle finger. When the vibration ended, the subject estimated an
      interval identical to its length before pressing a response button. The control
      task used cued responses with comparable intervals and stimuli. The pattern of
      activation obtained in the timing task as compared to control mainly included
      areas having attentional functions (the right dorsolateral prefrontal, inferior
      parietal, and anterior cingulate cortices), and the supplementary motor area
      (SMA). No significant difference was seen as a function of the duration range. It
      is argued, firstly, that involvement of the attentional areas derives from
      specific relations between attention and the temporal accumulator, as described
      by dominant timing models; and, secondly, that the SMA, or more probably one of
      its subregions, subserves time processing.

PMID- 11845245
TI  - Effects of atropine on the central mechanism of deglutition in anesthetized
      sheep.
AB  - The role of acetylcholine in the central mechanism of swallowing remains a matter
      of debate. The aim of this work, conducted in sheep, was to assess the effects of
      anti-muscarinic drugs (mainly atropine) on the activity of peripheral muscles
      involved in the oropharyngeal and esophageal phases of swallowing, and on that of
      dorsal medulla interneurons which program swallow-induced esophageal contractions
      and therefore belong to the so-called central pattern generator. Our results were
      obtained in anesthetized animals by means of electromyographic and manometric
      recordings of peripheral muscle contractions associated with microelectrode
      recordings of medullary interneuron discharge. They show that both interneuron
      discharge and primary esophageal contractions that follow the oropharyngeal
      component of swallowing were suppressed under atropine (0.1--0.5 mg/kg). In
      contrast, atropine did not impede the swallowing oropharyngeal component, the
      secondary peristalsis and the "deglutitive inhibition," which affects the
      esophageal motility during the oropharyngeal phase of swallowing. In conclusion,
      muscarinic receptors (probably not those of M(1)type) appear to control the
      primary peristalsis, but neither the secondary peristalsis nor the deglutitive
      inhibition.

PMID- 11845244
TI  - Dynamic visual acuity during passive and self-generated transient head rotation
      in normal and unilaterally vestibulopathic humans.
AB  - To determine whether dynamic visual acuity (DVA) during head rotations on the
      stationary body can lateralize unilateral vestibular deafferentation and detect
      non-labyrinthine compensation mechanisms, 15 normal and 11 subjects with
      unilateral vestibular deafferentation underwent manually imposed and self
      generated transient yaw head rotations during measurement of binocular DVA. DVA
      was measured by a four-alternative, forced choice, staircase procedure with
      optotype presentation only when head velocity exceeded thresholds of 50 degree or
      75 degree/s. Eye and head movements were recorded using search coils to
      characterize ocular motor strategies. During directionally unpredictable,
      manually imposed contralesional rotation, unilaterally deafferented subjects had
      decreases in DVA from the static condition of 0.36 +/- 0.22 and 0.47 +/- 0.53 log
      of the minimum angle resolvable (logMAR, mean +/- SD), respectively, for 50
      degree and 75 degree/s thresholds, not significantly greater than those of normal
      subjects (0.26 +/- 0.13 and 0.36 +/- 0.14, P>0.05). However, during manually
      imposed ipsilesional rotation, vestibulopathic subjects had decreases in DVA of
      0.66 +/- 0.36 and 1.08 +/- 0.47 logMAR, significantly greater than during
      contralesional rotation ( P<0.01). The DVA reduction difference for the ipsi- and
      contralesional directions was less during self-generated than during manually
      imposed head rotations. The directional difference for manually administered head
      rotations yielded a robust diagnostic measure with essentially no overlap in
      performance with normal subjects. Diagnostic performance for DVA during self
      generated head rotation was poorer. Recordings of eye and head movements made
      using search coils during DVA testing confirmed a deficient vestibulo-ocular
      reflex (VOR) during ipsilesional rotation, with most unilaterally vestibulopathic
      subjects employing predictive smooth eye movements and vestibular catch-up
      saccades. Measurement of DVA during transient head rotation on the body thus
      reliably can detect and lateralize vestibular pathology and compensatory
      mechanisms. Extravestibular mechanisms for compensation appear more effective
      during self-generated than manually imposed head rotations.

PMID- 11845246
TI  - Early phylogenetic value of the major GABA(A) receptor subunit mRNAs in the
      telencephalon.
AB  - In an effort to establish distinct phylogenetic values for the major GABA(A)
      receptor subunit mRNAs (alpha(1), beta(2) and gamma(2)) in the telencephalon, the
      cellular expression capacity of these mRNAs was evaluated in this brain region of
      two distantly related mammals (hedgehog and rat). Application of emulsion
      hybridization histochemistry and quantitative film autoradiography approaches
      allowed us to detect elevated ( P<0.01) beta(2) mRNA levels in primitive
      telencephalic neuronal populations such as those of the glomerular olfactory
      layer of the hedgehog. Conversely, notable levels of the alpha(1)-subunit mRNA
      were also registered for the higher telencephalic regions such as the oriens
      pyramidalis layer of the hippocampus although elevated levels were mostly
      obtained for the rat. Interestingly, it was the high number of giant pyramidal
      neurons that were actively involved in the expression of this subunit. A similar
      pattern was also detected for pyramidal-like cells of the rat lateral amygdala
      region expressing the gamma(2)-subunit mRNA. Taken together, these results
      suggest an early phylogenetic success of GABAergic neuronal mechanisms relying
      mainly on elevated beta(2)-subunit levels. On the other hand, elevated quantities
      of gamma(2)- and, above all, of alpha(1)-subunit mRNAs in the rat seem instead to
      be related to the highly advanced behavioral and mnemonic strategies that are
      under the control of these telencephalic regions.

PMID- 11845247
TI  - Ocular fixation and visual activity in the monkey lateral intraparietal area.
AB  - The macaque lateral intraparietal area (LIP) has been implicated in visuospatial
      attention and saccade planning. Since area LIP also contains a representation of
      the central visual field, we investigated its possible role in fixation and
      foveal attention in a visual fixation task with gap (momentary disappearance of
      fixation point). In addition to the expected visual neurons ( n=119), two main
      categories were identified: (1) cells responding tonically both during the
      presence and momentary absence of the fixation stimulus( n=47); a subset of these
      neurons studied in a saccade task showed perisaccadic inhibition in half of the
      cases (14/27). The timing of this inhibition, however, is only loosely related to
      saccade timing; (2) cells responding mainly to the absence of the fixation
      stimulus, with either abrupt or gradual onset of activity during the gap ( n=62).
      During saccades, these neurons showed presaccadic buildup and/or postsaccadic
      activity, which was spatially tuned in about half of the tested cells (28/53).
      Ninety-one percent of the cells in the first category and 59% of the cells in the
      second category were located in the dorsal portion of area LIP (LIPd). These
      results are consistent with the hypothesis of an oculomotor-attentional network
      contributing to fixation engagement and disengagement in a subregion of LIP.

PMID- 11845249
TI  - Attentional control in learning to discriminate bars and gratings.
AB  - Transfer effects of learning a spatial-frequency and a bar-width discrimination
      task on the performance in three other discrimination tasks (relative bar
      position, local width, and global-size discrimination) have been investigated. In
      the spatial-frequency discrimination learning task, subjects were trained with
      grating stimuli which varied in spatial frequency, relative bar position, and
      grating patch size, but only spatial frequency was relevant for discrimination.
      The bar-width discrimination learners had to judge the width of single grating
      bars appearing at random positions distributed around a display center. During
      the course of 10 consecutive days, all subjects showed a significant reduction of
      discrimination thresholds. Regarding learning transfer, we find that practicing
      the spatial-frequency discrimination task yields quite strong improvement of bar
      width discrimination and, vice versa, learning bar-width discrimination also
      leads to strong improvement of spatial-frequency discrimination performance,
      indicating involvement of coding pathways which are shared by both tasks. On the
      other hand, there is no performance improvement when subjects do different tasks
      (grating patch size and relative bar position discrimination) with the same
      stimulus material as the learning stimuli. The finding of task-driven selective
      learning for only one local stimulus attribute among other local and global
      attributes shows that feature-based attentional preselection of basic stimulus
      attributes is involved in learning. Moreover, differential learning effects for
      two different local stimulus features indicate that, governed by top-down
      control, different neural pathways starting from the same low-level code base may
      be formed in the course of discrimination training.

PMID- 11845248
TI  - Prefrontal lesions impair the implicit and explicit learning of sequences on
      visuomotor tasks.
AB  - OBJECTIVE: (1) To verify whether the prefrontal cortex (PFC) is specifically
      involved in visuomotor sequence learning as opposed to other forms of motor
      learning and (2) to establish the role of executive functions in visuomotor
      sequence learning. BACKGROUND: Visuomotor skill learning depends on the integrity
      of the premotor and parietal cortex; the prefrontal cortex, however, is essential
      when the learning of a sequence is required. METHODS: We studied 25 patients with
      PFC lesions and 86 controls matched for age and educational level. Participants
      performed: (1) a Pursuit Tracking Task (PTT), composed of a random tracking task
      (perceptual learning) and a pattern tracking task (explicit motor sequence
      learning with learning indicated by the decrease in mean root square error across
      trial blocks), (2) a 12-item sequence version of a serial reaction time task
      (SRTT) with specific implicit motor sequence learning indicated by the rebound
      increase in response time when comparing the last sequence block with the next
      random block, and (3) a neuropsychological battery that assessed executive
      functions. RESULTS: PFC patients were impaired in sequence learning on the
      pattern tracking task of the PTT and on the SRTT as compared to controls, but
      performed normally on the PTT random tracking task. Learning on the PTT did not
      correlate with learning on the SRTT. PTT performance correlated with planning
      functions while SRTT performance correlated with working memory capacity.
      CONCLUSIONS: The PFC is specifically involved in explicit and implicit motor
      sequence learning. Different PFC regions may be selectively involved in such
      learning depending on the cognitive demands of the sequential task.

PMID- 11845250
TI  - Understanding the contribution of binocular vision to the control of adaptive
      locomotion.
AB  - Abstract. Although the contribution of binocular vision to reach-to-grasp
      movements has been extensively studied, it has been largely ignored in
      locomotion. The aim of these studies was to explore the role of binocular vision
      during the approach phase and step over the obstacle and the contribution of head
      movements to acquisition of depth information under monocular vision. Binocular
      and monocular vision was manipulated in different phases using either an eye
      patch or liquid crystal glasses. Head movement relative to the trunk was
      restricted in the first experiment by a modified Ferno Universal Head Immobilizer
      attached to a rigid board strapped to the participant's back. Whole body
      kinematics were collected by placing infrared diodes on anatomical landmarks and
      using an Optotrak imaging system. Several measures related to head and limb
      movement were analyzed. Three major findings emerged from these studies. First,
      binocular vision is important for the acquisition of accurate information about
      the surrounding environment: accuracy but not precision of limb elevation over
      the obstacle was adversely affected when binocular vision was unavailable.
      Second, motion parallax due to self-motion provides the most critical depth
      information and it can be used to partially compensate for the loss of binocular
      vision. Although head movement is not essential to augment depth information, it
      is important for reorientation of the visual field to obtain the necessary
      information about the moving limbs when visual field is suddenly limited under
      monocular vision. Third, step over the obstacle is pre-planned based on visual
      information acquired during the approach phase: changes in visual condition
      during the adaptive step do not influence the limb trajectory. Collectively these
      three studies provide unique insights into the contribution of binocular vision
      during adaptive locomotion.

PMID- 11845251
TI  - Modulation of rodent cortical motor excitability by somatosensory input.
AB  - It is assumed that somatosensory input is required for motor learning and
      recovery from focal brain injury. In rodents and other mammals, corticocortical
      projections between somatosensory and motor cortices are modified by patterned
      input. Whether and how motor cortex function is modulated by somatosensory input
      to support motor learning is largely unknown. Recent human evidence suggests that
      input changes motor excitability. Using transcranial magnetic stimulation (TMS),
      this study tested whether motor cortex excitability is affected by patterned
      somatosensory stimulation in rodents. Motor potentials evoked in gastrocnemius
      muscles in response to TMS (MEP(TMS)) and to cervical electrical stimulation
      (MEP(CES)) were recorded bilaterally. Initially, the first negative peak of the
      MEP(TMS) was identified as a cortical component because it disappeared after
      decortication in three animals. Subsequently, we studied the effects of 2 h of
      electrical stimulation of one sciatic nerve on the cortical component of the
      MEP(TMS), i.e., on motor cortex excitability. After stimulation, its amplitude
      increased by 117 +/- 45% ( P<0.01) in the stimulated limb. A significantly
      smaller effect was found in the unstimulated limb ( P<0.02) and no effect was
      observed in unstimulated control animals. The subcortically evoked MEP(CES) were
      not affected by stimulation. It is concluded that somatosensory input increases
      motor excitability in rat. This increase outlasts the stimulation period and is
      mediated by supraspinal structures, likely motor cortex. Modulation of motor
      cortex excitability by somatosensory input may play a role in motor learning and
      recovery from lesion.

PMID- 11845252
TI  - Representation of sound source direction in the superior colliculus of the guinea
      pig in a virtual auditory environment.
AB  - The deep layers of the superior colliculus (SC) receive visual, auditory, and
      somatosensory input. A major function of the SC is the control of orientation
      movements of the eye, head, and pinna. While a topographical map for sound source
      direction remains elusive in primary auditory structures of mammals, such a map
      for azimuthal sound source directions has been reported in the deep layers of the
      SC. Moreover, a gradient of elevation tuning has been also seen in the SC of
      ferrets and cats. Here we demonstrate that a virtual auditory environment can be
      used to reveal azimuthal and elevational topography for auditory spatial
      receptive fields in neurons in the SC of guinea pigs. Individual, head-related
      transfer functions (HRTF) were measured in ten guinea pigs for 122 directions in
      the upper hemispheric field and convolved with white noise. Many neurons (39%) in
      the deep layers showed robust responses to these virtual sounds, and the majority
      of these neurons had small spatial receptive fields that were restricted to the
      contralateral hemifield. Best directions varied from 0 degree to 135 degree
      azimuth along the contralateral side and from --10 degree to 60 degree elevation.
      Like previous studies using free-field stimulation, a gradient of best azimuth
      direction was found along the rostral-caudal axis, with rear directions
      represented caudally and front directions rostrally. The topographical
      organization for best elevations had not been studied previously in the guinea
      pig. We found that it roughly followed the mediolateral axis, with preference for
      high elevations represented medially and low elevations laterally. A similar
      organization using free-field stimulation has been reported in the ferret.

PMID- 11845254
TI  - Killing activity of human umbilical cord blood-derived TCRValpha24(+) NKT cells
      against normal and malignant hematological cells in vitro: a comparative study
      with NK cells or OKT3 activated T lymphocytes or with adult peripheral blood NKT
      cells.
AB  - PURPOSE: We aimed to determine the effects of human umbilical cord blood (UCB)
      derived natural killer T (NKT) cells as immunological effectors against
      hematological malignancies, as well as auto- or allo-dendritic cells (DCs) or EB
      transformed cell lines (EBCLs). MATERIALS: TCRValpha24(+) Vbeta11(+) UCB- or PB
      NKT cells were isolated by sorting and activated by alpha-galactosylceramide
      pulsed autologous DCs. UCB-NK cells were induced from CD34(+) cells by stem cell
      factor plus IL-15. UCB-T cells were primarily activated by anti-CD3 monoclonal
      antibody. All those effectors were cultured with IL-2 (100 U/ml), and their
      cytotoxic activities were evaluated by (51)Cr-release assay. UCB-NKT cells were
      cultured with IL-12, IL-18 or higher dose of IL-2 (1000 U/ml), and again tested
      for the cytotoxicity against selected targets. RESULTS: UCB-NKT cells exhibited a
      pattern of killing activity against various hematological malignancies similar to
      that of UCB-NK cells, but could not kill K562, which was a vulnerable target for
      NK cells. The level of activity was quite similar to that of PB-NKT cells. In
      contrast, OKT-3-activated UCB-T lymphocytes showed a stronger and wider spectrum
      of killing compared with UCB-NK or NKT cells. IL-12, IL-18 or a higher dose of IL
      2 upregulated the activity; however several targets, including fresh leukemic
      cells, still remained resistant. NKT cells killed auto- or allo-DCs at a level
      similar to that of T cells, but could not kill allo-EBCLs, which were efficiently
      killed by T cells. While NK cells showed only marginal or no killing against DC
      or EBCLs. DISCUSSION: The anti-cancer activity of human NKT cells depends on the
      concentrations or the combination of Th1-cytokines. Basically, those cells might
      not be contributing to the immune surveillance of hematological malignancies, as
      shown by a relatively low cytotoxicity against malignant cells, together with the
      quite strong killing against auto-DCs.

PMID- 11845256
TI  - Binding to CD20 by anti-B1 antibody or F(ab')(2) is sufficient for induction of
      apoptosis in B-cell lines.
AB  - CD20 is a B-cell-specific cell surface protein expressed on mature B lymphocytes
      and is a target for monoclonal antibody therapy for non-Hodgkin's lymphoma (NHL).
      Though clear clinical efficacy has been demonstrated with several anti-CD20
      antibodies, the mechanisms by which the antibodies activate CD20 and kill cells
      remain unclear. Proposed mechanisms of action include complement-dependent
      cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC), and
      induction of apoptosis. In this report we compared the activity of two anti-CD20
      antibodies, Anti-B1 Antibody (tositumomab) and rituximab (C2B8), in a variety of
      cellular assays using a panel of B-cell lines. Anti-B1 Antibody showed a low
      level of activity in a CDC assay against complement-sensitive B-cell lines, Ramos
      and Daudi. We found that there is an inverse correlation between the expression
      of CD55 and CD59 and CDC mediated by either Anti-B1 Antibody or rituximab.
      Rituximab was more potent at inducing CDC when compared to Anti-B1 Antibody.
      Using Raji cells as target cells and human peripheral blood leukocytes as
      effector cells, Anti-B1 Antibody was a potent inducer of ADCC. The activities of
      Anti-B1 Antibody and rituximab were nearly identical in the ADCC assay. In
      addition, Anti-B1 Antibody showed direct induction of apoptosis in all B-cell
      lines tested. In general, crosslinking Anti-B1 Antibody with a goat anti-mouse Ig
      did not further enhance the percentage of cells undergoing apoptosis.
      Importantly, a F(ab')(2) fragment of Anti-B1 Antibody induced apoptosis, while
      the Fab fragment did not, indicating that the Fc region was not required and
      dimerization of CD20 may be sufficient for induction of apoptosis. In contrast,
      rituximab, which binds to an overlapping epitope on CD20 with a three-fold lower
      affinity than Anti-B1 Antibody, did not efficiently induce apoptosis in the cell
      lines tested in the absence of crosslinking. In conclusion, these two anti-CD20
      antibodies have overlapping, but distinct mechanisms of action on B-cell lines.

PMID- 11845255
TI  - Vaccination of stage IV patients with allogeneic IL-4- or IL-2-gene-transduced
      melanoma cells generates functional antibodies against vaccinating and autologous
      melanoma cells.
AB  - The antibody (Ab) response to allogeneic Me14932 and autologous melanoma cells
      was analyzed in 13 Stage IV (AJCC) melanoma patients immunized with Me14932 cells
      transduced with the IL-4 (Me14932/IL-4) ( n=10) or IL-2 (Me14932/IL-2) ( n=3)
      gene. No Ab response was observed before the 4th vaccination. Among 8 patients
      that received four vaccinations, 3/5 patients vaccinated with Me14932/IL-4 cells
      developed Ab (IgG and/or IgM) to Me14932 ( n=3) and to autologous ( n=2) melanoma
      cells, and 2/3 patients vaccinated with Me14932/IL-2 cells developed Ab (IgG) to
      Me14932, but not to autologous melanoma cells. Further, among these 5 responding
      patients, circulating Ab against the HLA-A3 allele, expressed only on vaccinating
      cells, were identified in the immune sera of 4 patients immunized with Me14932/IL
      4 ( n=2) or Me14932/IL-2 ( n=2) cells. These sera mediated antibody-dependent
      cell cytotoxicity (ADCC) of Me14932 cells, and a direct correlation ( r=0.85;
      P=0.03) between intensity of staining (IgG) and extent of lysis was found. Immune
      serum of one of these patients also induced ADCC of autologous melanoma cells,
      and serum from another patient mediated complement cytotoxicity of Me14932, but
      not of autologous melanoma cells. Thus, Abs against vaccinating and autologous
      melanoma cells were generated in 62% of patients after four vaccinations with
      cytokine-transduced melanoma cells. These findings demonstrate that the
      identification and titration of alloreactive Ab helps to monitor the extent of
      immunization against cellular vaccines, while the induction of Ab reactive to
      antigens shared between vaccinating and autologous melanoma cells may contribute
      to their therapeutic efficacy.

PMID- 11845257
TI  - Generation of activated and antigen-specific T cells with cytotoxic activity
      after co-culture with dendritic cells.
AB  - Co-culturing of immunological effector cells with antigen-pulsed DC leads to an
      increase of cytotoxic activity against antigen-expressing tumour cells. Using
      this approach, we could detect up to 2.8% antigen-specific CTLs after co-culture
      with antigen-pulsed DC. However, the required high effector cell numbers remain a
      major obstacle in immunotherapy. In this study, we show an approach for
      generating activated and antigen-specific effector cells that enables us to
      decrease effector to target cell ratios. We used an interferon-gamma secretion
      assay to enrich activated effector cells after co-culture with antigen-pulsed
      dendritic cells (DC). Purified immunological effector cells lysed 58.3% of
      antigen-expressing tumour cells at an effector to target ratio of 1:1.
      Furthermore, using MHC-IgG complexes, we enriched effector cells expressing
      antigen-specific T-cell receptor after co-culture with DC. Performing ELISpot,
      flow cytometry and TCR analysis, we could show a significant increase of
      activated and specific TCR-expressing effector cells after co-culture with DC.

PMID- 11845258
TI  - A mutated superantigen SEA D227A fusion diabody specific to MUC1 and CD3 in
      targeted cancer immunotherapy for bile duct carcinoma.
AB  - In cancer immunotherapy research, many bispecific antibodies (BsAbs) have been
      developed for directing T cells toward tumor cells. Recent advances in genetic
      engineering have made it possible to prepare immunoglobulin fragments consisting
      of variable domains using bacterial expression systems. Therefore, recombinant
      BsAbs, termed diabodies, have attracted particular attention. We have previously
      produced an anti-MUC1 x anti-CD3 diabody (Mx3 diabody) in an Escherichia coli (
      E. coli) expression system. In order to reinforce the antitumor effects of the
      Mx3 diabody, mutated superantigen staphylococcal enterotoxin A (SEA) D227A was
      genetically fused to the Mx3 diabody. The SEA D227A fusion Mx3 diabody (SEA D227A
      Mx3 diabody) thus constructed showed remarkable MUC1-specific antitumor effects
      when used with effector cells (lymphokine-activated killer cells with T-cell
      phenotype [T-LAK] and peripheral blood mononuclear cells [PBMCs]). In the bile
      duct carcinoma (BDC)-xenografted severe combined immunodeficient (SCID) mouse
      model, it also demonstrated strong antitumor activity when administered i.v.
      together with T-LAK cells and interleukin-2 (IL-2). In this experiment, the
      complete disappearance of tumors was observed in 3 out of 6 mice, and the other 3
      showed marked retardation of tumor growth. Therefore, the SEA D227A-Mx3 diabody
      is considered to be a promising reagent in specific targeted immunotherapy for
      BDC and other MUC1-positive carcinomas. This is the first report on a diabody
      that is effective in treating human solid cancers in the xenografted SCID mouse
      experimental model.

PMID- 11845259
TI  - Vaccination with autologous tumour antigen-pulsed dendritic cells in advanced
      gynaecological malignancies: clinical and immunological evaluation of a phase I
      trial.
AB  - Dendritic cell (DC)-based therapy has proven to be effective in patients with
      malignant lymphoma, melanoma, and renal and prostate carcinoma. In this phase I
      clinical trial, we have shown that patients with advanced gynaecological
      malignancies can be effectively vaccinated with DC pulsed with keyhole limpet
      haemocyanin (KLH) and autologous tumour antigens. Two patients with uterine
      sarcoma and six subjects with ovarian carcinoma received three to 23
      intracutaneous injections of antigen-pulsed DC at 10-day or 4-week intervals.
      Three patients showed stable disease lasting 25 to 45 weeks, and five experienced
      tumour progression within the first 14 weeks. KLH- and tumour lysate-specific
      delayed-type hypersensitivity (DTH) reactions were observed in six and one
      patient, respectively. Lymphoproliferative responses to KLH and to tumour lysate
      stimulation were recorded in six patients and in two patients respectively.
      Tumour antigen-stimulated interferon-gamma (IFN-gamma) secretion by peripheral
      blood mononuclear cells (PBMC) in one patient was consistent with a T(H) type 1
      cytokine bias. The treatment was safe, well tolerated, immunologically active and
      except for local cutaneous hypersensitivity devoid of significant adverse
      effects.

PMID- 11845260
TI  - The presence of interleukin-2 receptor alpha in the serum of colorectal cancer
      patients is unlikely to result only from T cell up-regulation.
AB  - It is unclear whether the presence of interleukin-2 soluble receptor alpha (IL-2
      sRalpha) in the serum of colorectal cancer patients is solely due to T cell
      activation. In this study, we therefore investigated whether T cell activation,
      indicated by the up-regulation of the CD25 and HLA-DR markers, or cell-mediated
      immunity (CMI) were associated with increased serum levels of IL-2 sRalpha in
      patients with advanced colorectal carcinoma. The levels of serum IL-2 sRalpha and
      the proportion of T cells expressing HLA-DR (DR(+) T cells) were measured as
      markers for chronic activation. CMI was assessed by delayed-type hypersensitivity
      reaction (DTH) to intradermal injections of recall antigens. Eighty-seven
      colorectal liver metastases (CLM) patients and 23 'cancer-free' control subjects
      were studied. DR(+) T cells were found to be more prevalent ( P<0.0001) in CLM
      patients (median: 21.1%) than in controls (median: 3.4%), but DR(+) T cell up
      regulation was not correlated with serum IL-2 sRalpha levels. CMI positivity was
      significantly reduced ( P=0.002) in CLM patients compared with controls, and this
      reduction was significantly associated ( P=0.05) with an increase in the number
      of DR(+) T cells. Although survival was significantly shorter ( P=0.0003) in
      patients with increased serum IL-2 sRalpha levels than in subjects with normal
      levels, no association was found between survival and DR(+) T cell up-regulation.
      These findings were consistent with the hypothesis of an additional source of
      serum IL-2 sRalpha other than T cell up-regulation in CLM patients -- either from
      other immune cells, or from tumour products.

PMID- 11845261
TI  - Progress in vaccination against cancer (PIVAC) 2001, Robinson College, University
      of Cambridge, UK.

PMID- 11845282
TI  - Microinsemination, nuclear transfer, and cytoplasmic transfer: the application of
      new reproductive engineering techniques to mouse genetics.

PMID- 11845283
TI  - Retrotransposed genes such as Frat3 in the mouse Chromosome 7C Prader-Willi
      syndrome region acquire the imprinted status of their insertion site.
AB  - Prader-Willi syndrome (PWS) results from loss of function of a 1.0- to 1.5-Mb
      domain of imprinted, paternally expressed genes in human Chromosome (Chr) 15q11
      q13. The loss of imprinted gene expression in the homologous region in mouse Chr
      7C leads to a similar neonatal PWS phenotype. Several protein-coding genes in the
      human PWS region are intronless, possibly arising by retrotransposition. Here we
      present evidence for continued acquisition of genes by the mouse PWS region
      during evolution. Bioinformatic analyses identified a BAC containing four genes,
      Mkrn3, Magel2, Ndn, Frat3, and the Atp5l-ps1 pseudogene, the latter two genes
      derived from recent L1-mediated retrotransposition. Analyses of eight overlapping
      BACs indicate that these genes are clustered within 120 kb in two inbred strains,
      in the order tel-Atp5l-ps1-Frat3-Mkrn3-Magel2-Ndn-cen. Imprinting analyses show
      that Frat3 is differentially methylated and expressed solely from the paternal
      allele in a transgenic mouse model of Angelman syndrome, with no expression from
      the maternal allele in a mouse model of PWS. Loss of Frat3 expression may,
      therefore, contribute to the phenotype of mouse models of PWS. The identification
      of five intronless genes in a small genomic interval suggests that this region is
      prone to retroposition in germ cells or their zygotic and embryonic cell
      precursors, and that it allows the subsequent functional expression of these
      foreign sequences. The recent evolutionary acquisition of genes that adopt the
      same imprint as older, flanking genes indicates that the newly acquired genes
      become 'innocent bystanders' of a primary epigenetic signal causing imprinting in
      the PWS domain.

PMID- 11845284
TI  - Spam1 (PH-20) mutations and sperm dysfunction in mice with the Rb(6.16) or
      Rb(6.15) translocation.
AB  - In mice bearing the Rb(6.16) or Rb(6.15) Robertsonian translocation (Rb), sperm
      dysfunction associated with the Rbs has been shown to lead to transmission ratio
      distortions (TRDs) in heterozygotes. The severity of the TRDs is directly related
      to the severity in the alteration of expression of the gene for the Sperm
      Adhesion Molecule 1 (Spam1), which maps to proximal mouse Chromosome 6 (Chr 6)
      near the translocation junction and encodes a sperm antigen with hyaluronidase
      activity. Here we demonstrate that there is a significantly reduced fertility in
      the Rb homozygotes (P < 0.001), based on litter size; and that with the Sperm
      Select Penetration assay Rb-bearing sperm have significantly decreased (P < 0.02
      0.001) rates of penetration of hyaluronic acid. Catalytic kinetics studies
      indicate that reduced Spam1 (PH-20) hyaluronidase activity in the Rb(6.15) mice
      results from a qualitative defect, while for Rb(6.16) with the greater TRD both a
      qualitative and a quantitative deficiency (confirmed by Western analysis) of
      Spam1 exist. Six point mutations were shown to be clustered in the Spam1
      hyaluronic acid-binding domain in Rb(6.15). For Rb(6.16) which has a gross
      genomic alteration at the Spam1 locus, 11 point mutations are scattered in the 5'
      and 3' UTRs and the coding region, where one leads to the replacement of a
      conserved residue. Entrapment of spontaneous Spam1 mutations, owing to
      recombination suppression near the Rb junctions, is proposed as the major
      underlying defect of the sperm dysfunction.

PMID- 11845285
TI  - Rapid decrease of RNA level of a novel mouse mitochondria solute carrier protein
      (Mscp) gene at 4-5 weeks of age.
AB  - We cloned a novel mouse gene that encodes a protein with homology to the
      mitochondria solute carrier proteins (Mscp). The major full-length Mscp
      transcript contains 4112 bp of cDNA and a deduced protein of 338 amino acids. The
      Mscp protein shares 50%, 40%, and 39% sequence identity with the C. elegans
      hypothetical protein T26089 and the yeast mitochondria carrier proteins MRS3 and
      MRS4, respectively. It also showed homology with the uncoupling proteins (UCP1,
      UCP2, and UCP3; 22%, 24%, and 29% identity, respectively). The protein has six
      transmembrane domains and three mitochondria energy-transfer protein signature
      motifs, which are conserved among all the members of mitochondria carrier protein
      family. Northern analysis indicated that the Mscp gene is highly expressed in the
      spleen. Using cDNA microarray and Northern analysis, we have shown a significant
      decrease of the splenic Mscp mRNA levels around 4-5 weeks of age in several mouse
      strains including C57BL/6J, nonobese diabetic (NOD), and several NOD-congenic
      mice. These results suggest that the Mscp gene is decreased during splenic
      lymphocyte maturation in these mice.

PMID- 11845286
TI  - Quantitative trait loci affecting clinical mastitis and somatic cell count in
      dairy cattle.
AB  - Norway has a field recording system for dairy cattle that includes recording of
      all veterinary treatments on an individual animal basis from 1978 onwards.
      Application of these data in a genome search for quantitative trait loci (QTL)
      verified genome-wise significant QTL affecting clinical mastitis on Chromosome
      (Chr) 6. Additional putative QTL for clinical mastitis were localized to Chrs. 3,
      4, 14, and 27. The comprehensive field recording system includes information on
      somatic cell count as well. This trait is often used in selection against
      mastitis when direct information on clinical mastitis is not available. The
      absence of common QTL positions for the two traits in our study indicates that
      the use of somatic cell count data in QTL studies aimed for reducing the
      incidence of mastitis should be carefully evaluated.

PMID- 11845289
TI  - Cerd4, third member of the d4 gene family: expression and organization of genomic
      locus.
AB  - Two members of the d4 family of presumptive transcription modulators, neuro-d4
      (Neud4) and ubi-d4/Requiem (Req), have been characterized previously. We cloned
      and characterized the third member of this gene family, cer-d4 (Cerd4), from
      chicken and mouse cDNA libraries. The expression patterns of Cerd4 gene in both
      species are similar and more restricted than expression patterns of other two d4
      genes. The main sites of Cerd4 expression are retina and cerebellum, where
      multiple transcripts could be detected. Two major types of Cerd4 proteins are a
      full-length isoform possessing all domains characteristic to the d4 family and
      truncated XZ isoform without C-terminal tandem of PHD fingers. The developmental
      kinetics of expression of these isoforms is different. The intron/exon structure
      of human Cerd4 gene is similar to that of neuro-d4 and ubi-d4/Requiem genes, but
      most introns of Cerd4 gene are much larger than the corresponding introns of the
      other two genes.

PMID- 11845288
TI  - MACF1 gene structure: a hybrid of plectin and dystrophin.
AB  - Mammalian MACF1 (Macrophin1; previously named ACF7) is a giant cytoskeletal
      linker protein with three known isoforms that arise by alternative splicing. We
      isolated a 19.1-kb cDNA encoding a fourth isoform (MACF1-4) with a unique N
      terminus. Instead of an N-terminal actin-binding domain found in the other three
      isoforms, MACF1-4 has eight plectin repeats. The MACF1 gene is located on human
      Chr 1p32, contains at least 102 exons, spans over 270 kb, and gives rise to four
      major isoforms with different N-termini. The genomic organization of the actin
      binding domain is highly conserved in mammalian genes for both plectin and BPAG1.
      All eight plectin repeats are encoded by one large exon; this feature is similar
      to the genomic structure of plectin. The intron positions within spectrin repeats
      in MACF1 are very similar to those in the dystrophin gene. This demonstrates that
      MACF1 has characteristic features of genes for two classes of cytoskeletal
      proteins, i.e., plectin and dystrophin.

PMID- 11845290
TI  - An F344 rat congenic for BB/DP rat-derived diabetes susceptibility loci Iddm1 and
      Iddm2.

PMID- 11845287
TI  - Identification of members of the Wnt signaling pathway in the embryonic pituitary
      gland.
AB  - Prop1 is one of several transcription factors important for the development of
      the pituitary gland. Downstream targets of PROP1 and other critical pituitary
      transcription factors remain largely unknown. We have generated a partial
      expression profile of the developing pituitary gland containing over 350
      transcripts, using cDNA subtractive hybridization between Prop1(df/df) and wild
      type embryonic pituitary gland primordia. Numerous classes of genes including
      transcription factors, membrane associated molecules, and cell cycle regulators
      were identified in this study. Of the transcripts, 34% do not have sequence
      similarity to known genes, but are similar to ESTs, and 4% represent novel
      sequences. Pituitary gland expression of a number of clones was verified using in
      situ hybridization. Several members of the Wnt signaling pathway were identified
      in the developing pituitary gland. The frizzled2 receptor, Apc, beta-catenin,
      groucho, and a novel isoform of TCF4 (officially named Tcf7l2) were identified in
      developing pituitary libraries. Three N-terminal alternatively spliced Tcf7l2
      isoforms are reported here, each of which lacks a DNA-binding domain. Functional
      studies indicate that these isoforms can act as endogenous inhibitors of Wnt
      signaling in some contexts. This is the first report of Tcf7l2 and Fzd2
      expression in the developing pituitary. These molecules may be important in
      mediating Wnt signaling during pituitary ontogeny. We expect other transcripts
      from these libraries to be involved in pituitary gland development.

PMID- 11845291
TI  - Mapping of 93 porcine ESTs preferentially expressed in liver.

PMID- 11845292
TI  - Deletion of a direct repeat element has no effect on Igf2 and H19 imprinting.

PMID- 11845293
TI  - Proceedings of the First International Conference on the Secretion Defect in
      Cystic Fibrosis. May 5-8, 1999, Chalkidiki, Greece.

PMID- 11845294
TI  - Cystic fibrosis and CFTR.
AB  - Cystic fibrosis (CF) is a complex disease affecting epithelial ion transport.
      There are not many diseases like CF that have triggered such intense research
      activities. The complexity of the disease is due to mutations in the CFTR
      protein, now known to be a Cl(-) channel and a regulator of other transport
      proteins. The various interactions and the large number of disease-causing CFTR
      mutations is the reason for a variable genotype-phenotype correlation and
      sometimes unpredictable clinical manifestation. Nevertheless, the research of the
      past 10 years has resulted in a tremendous increase in knowledge, not only in
      regard to CFTR but also in regard to molecular interactions and completely new
      means of ion channel and gene therapy.

PMID- 11845295
TI  - Altered NaCl concentration of airway surface liquid in cystic fibrosis.
AB  - A novel isotopic technique suggests that the [Na] and [Cl] of airway surface
      liquid are both normally approximately 50 mM. In cystic fibrosis, lack of the
      functional cystic fibrosis transmembrane conductance regulator (CFTR) causes
      failure of transcellular Cl absorption, resulting in an elevation of [Na] and
      [Cl] of airway surface liquid to approximately 100 mM.

PMID- 11845296
TI  - Dynamics of protein and fluid secretion from the major salivary glands of rat:
      relevance of research findings to clinically observed defective secretion in
      cystic fibrosis.
AB  - Although there are indications of a defect in secretion of protein from exocrine
      cells in cystic fibrosis (CF), this remains an aspect of CF research that has not
      been adequately addressed. Using salivary glands of rat as model systems, and
      following the effects of parasympathetic and sympathetic autonomic nerve
      stimulation on these glands, we demonstrate the existence of three separate
      pathways through which secretion of protein can be evoked from serous and mucous
      exocrine cells. These pathways allow the secretion of proteins from the
      intracellular compartments in a constitutive, intermediate or regulated manner.
      The primary aspects of secretory profile including concentration and the degree
      of hydration of secreted material differ greatly between the pathways, are cell
      type specific, and presumably are a direct consequence of controlled changes in
      the levels of second messengers induced upon stimulation of these cells. As
      previously published reports suggest that only the beta-adrenergic regulated
      pathway is affected by CF, differences between the pathways in their secretory
      profiles may influence the development of lung disease, through disparate
      disturbances in the secretion of protein and fluid from serous and mucous cells
      of the submucosal glands that line the bronchiolar tree in humans. We gratefully
      acknowledge support from The Wellcome Trust and from The European Union Biomed II
      Programme.

PMID- 11845297
TI  - Effect of acute saline volume expansion in the anaesthetised DeltaF508 cystic
      fibrosis mouse.
AB  - It has been suggested that CFTR Cl(-) channels in the renal inner medullary
      collecting duct may be involved in mediating increased renal salt excretion
      during extracellular fluid volume expansion. To investigate this hypothesis, in
      vivo clearance experiments were performed comparing wild-type (WT) and DeltaF508
      CFTR transgenic mice (cftr (tm2Cam)). Control animals were given a 0.1-ml bolus
      of 0.9% saline, followed by I.V. infusion at 0.3 ml x h(-1). Volume expansion was
      applied by infusing a 1-ml bolus of 0.9% saline followed by infusion at 0.6 ml x
      h(-1). No significant differences in renal NaCl handling between WT mice (
      C(Na)=1.2 +/- 0.3 microl x min(-1), C(Cl)=4.0 +/- 0.5 microl x min(-1)) and
      DeltaF508-CFTR mice ( C(Na)=1.7 +/- 0.5 microl x min(-1), C(Cl)=4.1 +/- 0.8
      microl x min(-1)) were observed under control conditions. Volume expansion
      resulted in large significant increases in NaCl clearance in both WT mice (
      C(Na)=7.0 +/- 0.9 microl x min(-1), C(Cl)=12.0 +/- 0.6 microl x min(-1)) and
      DeltaF508-CFTR mice ( C(Na)=7.2 +/- 1.6 microl x min(-1), C(Cl)=11.0 +/- 2.2
      microl x min(-1)). However, there was no significant difference between WT and
      DeltaF508-CFTR mice. In conclusion, renal NaCl excretion is not significantly
      different under basal conditions and during saline volume expansion in DeltaF508
      CFTR mice. The data suggest that CFTR is not a physiologically important mediator
      of volume natriuresis.

PMID- 11845298
TI  - Electrodiffusional ATP movement through CFTR and other ABC transporters.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) is a member of the
      superfamily of ATP-binding cassette (ABC) transporters, also known as traffic
      ATPases. Recent studies from our laboratory determined that various members of
      the ABC family of transport proteins mediate the electrodiffusional movement of
      the nucleotide ATP. In this report, evidence for the movement of cellular
      nucleotides by the ABC transporter CFTR and related molecules, including P
      glycoproteins (Pgp), is reviewed. The wild-type mdr1 gene product, Pgp, enables
      the spontaneous release of cellular ATP. However, single amino acid substitutions
      in both nucleotide-binding sites render a dysfunctional Pgp, whose function can
      only be reversed by voltage activation. This report includes data indicating that
      reconstitution of highly purified CFTR from human epithelial origin enables the
      permeation of both Cl and ATP. The relevance of the ABC domains in ATP transport
      is also explored, and the hypothesis is forwarded that improper ATP transport by
      a dysfunctional CFTR is a relevant factor in cystic fibrosis.

PMID- 11845299
TI  - Ultrastructural changes in exocrine tissues of a DeltaF-508 CFTR mouse model.
AB  - Cystic fibrosis (CF) is characterized by abnormal secretion from epithelial
      cells. We wanted to detect changes in the ultrastructural characteristics of
      cells within a number of exocrine tissues, including the colon, submandibular and
      parotid salivary glands of DeltaF-508 CFTR animals. Therefore, in the present
      study a DeltaF-508 CFTR mouse model was compared to control, by applying
      conventional and complex carbohydrates staining techniques to tissue sections at
      the electron microscope level. The colon of DeltaF-508 CFTR mice contained thick
      mucous secretions that harbored many bacteria, along with cytoplasmic fragments
      and leukocytes. Leukocytes were also seen to infiltrate the cytoplasm of goblet
      cells. Tissues were taken before, 10 min after isoprenaline, and 30 min after a
      further injection of methacholine. In the submandibular gland, there is limited
      secretory activity after isoprenaline treatment, and this increases further with
      methacholine treatment. Depletion of the secretory granules of acinar cells is
      observed, following the combined isoprenaline and methacholine treatment, but no
      significant changes in granule numbers occurred in granular tubule cells.
      Glycogen, abundant before treatment, is reduced within 10 min of isoprenaline
      treatment and is completely exhausted by 30 min, especially in the convoluted
      granular tubule cells. A few secretory granules in acinar and in granular tubule
      cells of the DeltaF-508 CFTR submandibular glands displayed two electron
      densities. The secretory responses of the parotid gland cells were similar to
      those in submandibular gland cells, except that in these DeltaF-508 CFTR cells,
      secretory granules appeared more polymorphic in structure than those found in
      control animals.

PMID- 11845300
TI  - CFTR may play a role in regulated secretion by lymphocytes: a new hypothesis for
      the pathophysiology of cystic fibrosis.
AB  - Human lymphocytes and pancreatic acinar cells have a common function: both cell
      types secrete specific proteins in response to extracellular signals. Acinar
      cells secrete digestive enzymes, while lymphocytes secrete antibodies and
      cytokines. Both cell types utilize similar receptor-mediated activation systems,
      similar signal transduction pathways (i.e., alpha adrenergic receptors, and
      cAMP), and express the cystic fibrosis transmembrane conductance regulator
      (CFTR). Preliminary tests of the hypothesis that B lymphocytes are capable of
      regulated secretion were carried out using transformed lymphocytes. lambda light
      chain secretion rates were measured in response to treatment with 8-CPT-cAMP. A
      rapid transient increase in secretion was observed in non-CF lymphocytes. This
      effect was absent in CF lymphocytes. A failure of regulated secretion could cause
      a reduced response to antigen presentation, and an inability to completely clear
      pathogens such as Pseudomonas aeruginosa. Another piece of circumstantial
      evidence is that lung-transplanted CF patients remain chronically ill. While
      immunosuppressive therapy may contribute to the chronic illness, the phenomenon
      is more acute in CF lung-transplant patients than non-CF lung-transplant
      recipients receiving the same immunosuppressive therapy. A defect in regulated
      secretion of antibodies and cytokines in response to antigens may be the source
      of a long suspected, but as yet unproved CFTR-mediated immunological defect
      underlying the pulmonary morbidity and mortality in cystic fibrosis (CF).

PMID- 11845301
TI  - Relationship between IkappaBalpha deficiency, NFkappaB activity and interleukin-8
      production in CF human airway epithelial cells.
AB  - Several recent reports have suggested that airway inflammation may precede
      infection and relate to an endogenous dysregulation of pro-inflammatory cytokines
      in cystic fibrosis (CF) airways. Evidence suggests that activation of the nuclear
      factor kappa B (NFkappaB), which regulates the inflammatory gene transcription,
      depends on the degradation of the inhibitory factor IkappaBalpha. We show that,
      in in situ human DeltaF508 CF bronchial tissues, inhibitor factor IkappaBalpha is
      not present in gland cells, although endogenous levels of chemokine IL-8 are
      high. These data are confirmed by studying cultured CF human bronchial gland
      cells, in which a lack of cytosolic IkappaBalpha and high levels of activated
      NFkappaB, concomitant with IL-8 overproduction (a 13-fold increase) are found
      when compared to non-CF bronchial gland cells. Interestingly, treatment of CF
      gland cells with the isoflavone genistein, a well known CFTR mutant Cl(-) channel
      stimulator, results in a significant decrease ( P < 0.001) in IL-8 production
      down to levels released by non-CF gland cells. The addition of genistein also
      reverses the effects of lipopolysaccharide (LPS) Pseudomonas-aeruginosa-induced
      nuclear translocation of NFkappaB by increasing IkappaBalpha protein level (65%)
      in CF gland cells. Our data indicate that the induction of IkappaBalpha protein
      in CF airway glandular epithelial cells may be a novel mechanism by which IL-8
      mediated lung inflammatory events are markedly reduced in CF patients, at least
      at the airway glandular level.

PMID- 11845302
TI  - CFTR and lysozyme secretion in human airway epithelial cells.
AB  - Lysozyme is secreted in large quantities in human airways (10-20 mg/day), where
      it helps to defend against bacterial and fungal infection. Lysozyme expression is
      restricted to the serous cells of the submucosal glands, which also express high
      levels of cystic fibrosis transmembrane conductance regulator (CFTR) chloride
      channels. It is often assumed that mucus secretion in human airways is coupled to
      anion secretion through CFTR Cl(-) channels located in the apical membrane.
      Therefore, a defect in CFTR function could cause abnormal mucus secretion leading
      to persistent bacterial infection and inflammation of the airways. In this study
      we measured simultaneous secretion of lysozyme and Cl(-) from human airway
      epithelial serous cells. Secretion of lysozyme was measured by a turbidimetric
      assay that relies on the ability of lysozyme to disrupt the wall of the bacterium
      Micrococcus lysodeikticus, thus causing a fall in the optical density of the
      sample. Secretion of Cl(-) was measured as short-circuit current in a modified
      Ussing chamber. Activation of Cl(-) secretion by stimulation of cAMP- or Ca(2+)
      dependent pathways caused comparable increases in lysozyme secretion. Similarly,
      blockers of Cl(-) secretion, such as diphenylamine-2-carboxylate (DPC), also
      reduced lysozyme secretion. However, while treatment of airway submucosal gland
      cells with antisense oligonucleotides directed against CFTR reduced Cl(-)
      secretion, it had no significant effect on the total amount of lysozyme
      secretion. These results suggest a role for functional CFTR in regulation of
      lysozyme secretion in human airways.

PMID- 11845304
TI  - Altered sialyl- and fucosyl-linkage on mucins in cystic fibrosis patients
      promotes formation of the sialyl-Lewis X determinant on salivary MUC-5B and MUC
      7.
AB  - Destruction of the lungs as a consequence of recurrent infections with
      microorganisms such as Pseudomonas aeruginosa remains the underlying cause of
      most morbidity and mortality in cystic fibrosis (CF). We have hypothesized that
      changes in the glycosylation of key tracheal mucins such as MUC5B and MUC7 might
      increase the risk of pulmonary disease in CF patients. However, in preference to
      sputum we have examined the sugar-chains on these mucins in saliva because in the
      latter not only can the glycoproteins be collected from controls, but they are
      essentially free from modifications made following bacterial infection in
      disease. Proteins in ductal or whole-mouth saliva from 20 CF patients with the
      Delta F-508 CFTR mutation and age-and sex-matched controls were separated by SDS
      PAGE and blotted onto nitrocellulose and then probed with labelled lectins of
      known specificity. Linkage of terminal sialic acid on the blotted mucins was
      determined using Sambucus nigra agglutinin (detects the 2-->6 linkage) and
      Maackia amurensis agglutinin (the 2-->3 linkage). Fucose was detected by Ulex
      europaeus agglutinin-1 (1-->2 linkage) and Aleuria aurantia agglutinin (1-->3
      linkage). We found that each mucin shows a characteristic glycosylation pattern
      and in controls most of the sialic acid is 2-->6 linked on MG1 (MUC 5B) and 2-->3
      linked on MG2 (MUC 7). CF is associated with a shift from a 2-->6 linkage to a 2-
      >3 linkage on MG1 with some patients showing almost no 2-->6 linkage; 2-->3
      linkage on MG2 is similarly increased in disease in some individuals. The
      expression of fucose on these mucins is also raised in CF patients. These shift
      to a 2-->3 linkage of sialic acid, and with increased fucosylation this promotes
      the formation of sialyl-Lewis X antigen detected on CF mucins in our study. These
      changes will be tested for their correlation with the severity of lung disease.
      We gratefully acknowledge support from the European Union Biomed-II Programme.

PMID- 11845303
TI  - Sulphation of the salivary mucin MG1 (MUC-5B) is not correlated to the degree of
      its sialylation and is unaffected by cystic fibrosis.
AB  - Defective acidification of intracellular organelles, particularly the trans-Golgi
      network, has been proposed to explain the decreased sialylation and increased
      sulphation of secreted proteins in cystic fibrosis (CF). To test this hypothesis
      we compared expression of sulphate and sialic acid on three salivary mucins
      namely MG1 (MUC-5B), MG2 (MUC-7) and GL. Proteins in whole mouth saliva (WMS)
      from four individuals were separated by fast protein liquid chromatography (FPLC)
      on a Superdex 200 column and the partially purified mucins slot-blotted and
      assayed for sulphate content by staining with Alcian Blue. Sulphation varied with
      the individual and with the mucin: MG1 was the most sulphated and contributed
      almost the entire sulphate content of WMS. These results allowed us to test small
      volumes of WMS from 20 CF patients and age- and sex-matched controls for
      estimates of sulphate content on MG1. Wherever possible sulphate on MG1 was also
      visualised by staining washed SDS-PAGE gels with Alcian Blue at pH 1.0. To assess
      the sialic acid content of salivary mucins, electroblots of SDS-PAGE gels were
      probed with labelled Triticum vulgaris agglutinin. In summary, our results show
      MG1 to be the main sulphated protein in whole mouth saliva and there are large
      differences in the expression of sulphate and of sialic acid on this mucin, both
      in control and CF groups. CF led neither a decrease in sialylation nor an
      increase in sulphation and direct comparisons of sialic acid content with
      sulphate in MG1 failed to reveal any obvious link between the two in health or in
      disease. Our data thus do not support the hypothesis of defective acidification
      as the underlying cause of altered glycosylation in CF, but point instead to
      inter-individual differences in expression/functioning of terminal
      glycosyltransferases for published observations. We thank the European Union
      Biomed II programme for support.

PMID- 11845305
TI  - Molecular studies of CFTR interacting proteins.
AB  - Transport via the cystic fibrosis transmembrane conductance regulator (CFTR) is
      activated by its interactions with cytoplasmic cofactors, such as cAMP-activated
      protein kinases. CFTR activity is also known to couple to other ion channels and
      transporters. Although the genetic cause of human cystic fibrosis by CFTR
      mutations has been well established, little is known about the protein machinery
      that plays a role in linking the CFTR to other regulatory or ion-conducting
      proteins. Several regions of CFTR proteins are highly conserved among different
      species. The conserved motifs are thought to determine various aspects of channel
      and mediate interactions with other regulatory proteins. The C-termini, which are
      not required for functional expression of the CFTR chloride conductance, are also
      highly conserved. Several proteins that interact with the conserved C-terminus
      have now been identified. They contain several distinct protein interaction
      domains, which may be involved in the assembly of macromolecular CFTR channel
      complexes in vivo. Molecular understanding of these proteins may provide
      important insights into CFTR function in cystic fibrosis.

PMID- 11845306
TI  - Role of snare proteins in CFTR and ENaC trafficking.
AB  - The apical membrane ion channels, CFTR and ENaC, undergo regulated trafficking as
      a means of controlling their plasma membrane density. This provides a mechanism
      for regulating the Cl and Na conductance properties of epithelial apical
      membranes, and thus the transepithelial ion transport rates. Physical and
      functional interactions between these channels and SNARE proteins, in particular
      syntaxin 1A (S1A), provide a mechanism for linking the known vesicle fusion
      machinery with this process. In this paper we summarize evidence indicating that
      the interaction of S1A with CFTR and ENaC reduces channel currents in a syntaxin
      isoform-specific manner. The acute cAMP-regulated CFTR trafficking event, which
      is reported by an increase in membrane capacitance in response to cAMP, is also
      inhibited by exogenous S1A expression. We tagged both channels with flag epitopes
      on their extracellular surfaces to monitor their plasma membrane expression as a
      function of S1A co-expression. The data indicate that the reduction in current
      caused by S1A is associated with a marked decrease in the amount of CFTR or ENaC
      detected at the cell surface. These findings suggest that S1A inhibits ion
      channel insertion into the plasma membrane, either by disrupting the
      stoichiometry of SNARE protein associations that mediate channel trafficking, or
      by physically associating with the channels to prevent their insertion. These
      data link the SNARE machinery to the regulation of apical membrane ion channel
      density, and suggest that phosphorylation-dependent interactions of these
      channels with SNARE proteins may acutely regulate this process.

PMID- 11845307
TI  - Endocytic adaptor complexes bind the C-terminal domain of CFTR.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) functions at the
      apical membrane of epithelial cells to regulate chloride permeability. Recent
      studies have shown that CFTR is rapidly and efficiently internalized from the
      plasma membrane. We have shown that such internalization is mediated solely by
      clathrin-coated pathways, and that other pathways, such as caveolae, exclude
      CFTR. Moreover, CFTR co-precipitates with alpha-adaptin, a component of the
      endocytic adaptor complex (AP-2). The goal of our current studies was to
      elucidate further the molecular mechanisms that facilitate entry of CFTR into
      endocytic clathrin-coated vesicles. Protein-protein interactions generated by
      incubation of full-length in-vitro-translated CFTR with partially purified bovine
      brain adaptor complexes were evaluated following immunoprecipitation using an
      antibody against the alpha-adaptin subunit of the AP-2 complex. Such studies
      revealed co-immunoprecipitation of alpha-adaptin with full-length but not
      partially translated CFTR, suggesting that the C-terminus of CFTR may be
      responsible for this interaction. To test this hypothesis a C-terminal GST fusion
      protein (amino acids 1404-1480; CF-GST) was used in a "pull-down" assay with
      purified adaptor complexes. CF-GST sepharose was able to pull-down AP-2 endocytic
      adaptor complexes, as determined by immunoblot analyses of the precipitates using
      antibodies directed against alpha-adaptin. In contrast, CF-GST sepharose was
      unable to pull-down gamma-adaptin, a component of the Golgi-derived AP-1 clathrin
      adaptor complex. Thus, we demonstrate that CFTR is endocytosed via clathrin
      coated vesicles, and that targeting of CFTR to these structures is mediated by
      binding of the AP-2 adaptor complex to the C-terminal domain of CFTR.

PMID- 11845308
TI  - Role of actin filament organization in CFTR activation.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) is an anion
      selective channel whose dysfunction leads to the onset of cystic fibrosis. CFTR
      activation is normally elicited by stimulation of the cAMP pathway, which effects
      protein kinase A activation. However, previous studies from our laboratory
      indicate that the actin cytoskeleton is also required for a proper CFTR function.
      In this report, the regulatory role of actin filament organization in the
      activation of CFTR was explored. Maneuvers to modify the steady-state
      organization of actin filaments elicit the activation of CFTR in the absence of a
      functional cAMP pathway. Partial disruption of the actin cytoskeleton of CFTR
      expressing cells with cytochalasin D (CD) induced CFTR activation in the absence
      of an activated PKA. Similar findings were obtained by intracellular dialysis
      with the actin-severing protein gelsolin. However, extended treatment with CD
      leading to the collapse of the actin cytoskeleton rendered CFTR completely
      insensitive to direct PKA activation. cAMP activation of CFTR was also found to
      be dysfunctional in cells lacking the actin-crosslinking protein ABP-280, which
      was recovered after dialysis of the cells with filamin, a homologue of ABP-280.
      The present data indicate that an organized actin network is required for the
      proper cAMP-dependent activation of CFTR. The possibility is also explored that
      actin must be directly associated with CFTR to elicit its activation, further
      suggesting that this channel protein may bind actin as well.

PMID- 11845310
TI  - cAMP signaling cascades and CFTR: is there more to learn?
AB  - CFTR is an apically resident ion channel whose activity is regulated by the
      activation of the cAMP mediated second messenger cascade. As depicted in
      textbooks, the cAMP mediated signaling cascade appears deceptively simple, yet,
      our growing understanding of this pathway shows it to be much more complicated
      and finely tuned than originally thought. The intent of this review is to
      evaluate our current understanding of the cAMP mediated signaling as it relates
      to the secretion of mucin and chloride, two compounds whose regulated secretion
      is altered in cystic fibrosis.

PMID- 11845309
TI  - Regulation of gap junctional communication in CFTR-expressing pancreatic
      epithelial cells.
AB  - Gap junction channels provide a pathway for coordinating multicellular activity.
      To evaluate the contribution of cell-to-cell communication in the function of
      epithelial cells, we studied the strength of gap junctional coupling in
      pancreatic acinar and duct cells exposed to agents known to elevate the
      intracellular concentration of Ca(2+) or cAMP. In acinar cells, we observed that
      maximal concentrations of acetylcholine evoked a biphasic increase in cytosolic
      Ca(2+) mobilization. The second sustained phase, which depends on Ca(2+) influx
      into the cell, was associated with the rapid closure of gap junction channels. In
      duct cells, stimulation of CFTR-dependent Cl(-) currents with cAMP analogs
      markedly increased gap junctional conductance in pairs of cells. Interestingly,
      cAMP had no effect on intercellular communication between cells harboring the
      DeltaF508 mutation of CFTR. An abnormal pattern of gap junctional coupling may
      contribute to the altered functions of tissues affected in cystic fibrosis.

PMID- 11845311
TI  - Regulation of the CFTR channel by phosphorylation.
AB  - Cystic fibrosis transmembrane conductance regulator (CFTR) chloride channels are
      regulated tightly by protein kinases and phosphatases. The regulatory domain of
      CFTR has about 20 potential sites for phosphorylation by protein kinases A (PKA)
      and C (PKC). The reason for this large number of sites is not known, however
      their conservation from fish to humans implies that they play important roles in
      vivo. PKA is an important activator, and its stimulation of CFTR is enhanced by
      PKC via mechanisms which are not fully understood. The physiological stimuli of
      CFTR are not known for some epithelia, and it appears likely that other
      serine/threonine and even tyrosine kinases also regulate CFTR in particular
      tissues. Phosphatases that deactivate CFTR have yet to be identified definitively
      at the molecular level, however CFTR is regulated by a membrane-bound form of
      protein phosphatase-2C (PP2C) in several cell types. Patch-clamp studies of
      channel rundown, co-immunoprecipitation, chemical cross-linking studies, and pull
      down assays all indicate that CFTR and PP2C are closely associated within a
      stable regulatory complex. Understanding the regulation of CFTR by PP2C is a
      priority due to its potential as a target for pharmacotherapies in the treatment
      of cystic fibrosis.

PMID- 11845312
TI  - Nucleoside diphosphate kinase--a component of the [Na(+)]- and [Cl(-)]-sensitive
      phosphorylation cascade in human and murine airway epithelium.
AB  - We have shown that proteins within apically enriched fractions of human nasal
      respiratory epithelium vary their phosphohistidine content with ambient [Cl(-)]
      and other anion concentrations. This membrane-delimited phosphorylation cascade
      includes a multifunctional protein histidine kinase - nucleoside diphosphate
      kinase (NDPK). NDPK is itself a cascade component in both human and ovine airway,
      the self-phosphorylation of which is inhibited selectively by [Na(+)] in the
      presence of ATP (but not GTP). These findings led us to propose the existence of
      a dual anion-/cation-controlled phosphorylation-based "sensor" bound to the
      apical membrane. The present study showed that this cascade uses ATP to
      phosphorylate a group of proteins above 45 kDa (p45-group, identities unknown).
      Additionally, the Cl(-) dependence of ATP (but not GTP) phosphorylation is
      conditional on phosphatase activity and that interactions exist between the ATP-
      and GTP-phosphorylated components of the cascade under Cl(-)-free conditions. As
      a prelude to studies in cystic fibrosis (CF) mice, we showed in the present study
      that NDPK is present and functionally active in normal murine airway. Since NDPK
      is essential for UTP synthesis and regulates fetal gut development, G proteins,
      K(+) channels, neutrophil-mediated inflammation and pancreatic secretion, the
      presence of ion-regulated NDPK protein in mouse airway epithelium might aid
      understanding of the pathogenesis of CF.

PMID- 11845313
TI  - Non-CFTR chloride channels likely contribute to secretion in the murine small
      intestine.
AB  - While most cystic fibrosis (CF) transmembrane conductance regulator (CFTR)
      knockout animals die due to intestinal obstruction before or at the time of
      weaning, a subpopulation of these animals are long living and exhibit a milder
      phenotype. The decreased severity of intestinal disease in these mildly affected
      CF mice is related to the expression of non-CFTR genetic modifiers. The identity
      of these genetic modifiers is not known, but we hypothesize that they may
      complement CFTR function as a chloride channel in this tissue. To assess the
      contribution of non-CFTR chloride channels to chloride secretion across the small
      intestine of CF mice with mild disease, we measured the basal transepithelial
      potential difference across this tissue as well as the secretory response to
      agonists of the cAMP and the calcium-mediated signaling pathways. Chloride
      secretion across the small intestine of mildly affected CF mice was not
      stimulated by forskolin or by carbachol. The absence of CFTR is thus not
      compensated by the activity of a distinct, cAMP- or calcium-activated chloride
      channel at the apical surface of the intestinal epithelium. On the other hand, a
      basal chloride secretion across the intestinal epithelium was present in these
      animals, and we hypothesize that this activity may be linked to improved survival
      of these animals.

PMID- 11845314
TI  - Ca(2+)-activated Cl(-) channels: a newly emerging anion transport family.
AB  - A new family of chloride transport proteins has recently emerged. These proteins
      have extensive homology to a protein previously isolated from bovine tracheal
      epithelium that acts as a Ca(2+)-sensitive Cl(-) channel (CaCC) when
      heterologously expressed or when reconstituted into planar lipid bilayers.
      Several new members of this family have been identified in human, murine, and
      bovine epithelia, in addition to some other tissues, and are associated with
      Ca(2+)-sensitive conductive chloride transport when heterologously expressed in
      Xenopus oocytes or HEK 293 cells. The expressed current is also sensitive to
      inhibitors such as DIDS and niflumic acid. In addition, at least one family
      member acts as an endothelial cell adhesion molecule. This emerging family may
      underlie the Ca(2+)-mediated Cl(-) conductance responsible for rescue of the
      cystic fibrosis (CF) knockout mouse from significant airway disease.

PMID- 11845315
TI  - Gadolinium as an opener of the outwardly rectifying Cl(-) channel (ORCC). Is
      there relevance for cystic fibrosis therapy?
AB  - There is indirect evidence that the plasmalemma-integrated eukaryotic porin (the
      voltage-dependent anion-selective channel, VDAC) functions as the outwardly
      rectifying chloride channel (ORCC). The channel, which is believed to play a role
      in cell volume regulation, appears to be relevant for cystic fibrosis (CF)
      therapy, in that it may function as an alternative Cl(-) channel. In the present
      study we showed first that Gd(3+) altered the voltage dependence of human type-1
      porin incorporated into artificial planar lipid bilayers. Next, using a light
      scattering approach on transformed normal or CF human B-lymphocytes in hypotonic
      Ringer solution, we found slightly differing regulatory volume decrease (RVD)
      curves for the cell lines under study. Addition of 15-60 microM GdCl3 in
      hypotonic Ringer increased light scattering, pointing to cell swelling beyond
      normal values. RVD was not observed in those experiments. A corresponding effect
      was seen in isotonic Ringer containing GdCl3. In either osmotic situation Gd(3+)
      induced cell swelling was abolished by monoclonal mouse anti-human type-1 porin
      antibodies. Agonist and antibody effects were dose dependent. Finally,
      videocamera-monitored control experiments with adherent HeLa cells verified the
      direct effect of the agonist on cell swelling in hypo- or isotonic situations and
      its prevention by the antibodies. We conclude that GdCl3 opens plasmalemma
      integrated porin channels, allowing ions to following their gradients, resulting
      in cell swelling. Since respiratory epithelium expresses porin channels in the
      apical membrane, the use of gadolinium to activate ORCC may represent a new
      therapeutic approach in CF.

PMID- 11845316
TI  - Localisation of wild-type and DeltaF508-CFTR in nasal epithelial cells.
AB  - Wild-type and the DeltaF508 mutation of the cystic fibrosis transmembrane
      conductance regulator (DeltaF508-CFTR) were localised by confocal imaging in
      DeltaF508/DeltaF508 native airway epithelial cells using a well-characterised
      CFTR antibody. Surface nasal epithelial cells from three control and three CF
      individuals were obtained from nasal brushings. Cells were fixed, permeabilised
      and incubated with first antibody for 18 h at 4 degrees C. Following labelling
      with second antibody, cells were viewed with the confocal microscope. Wild-type
      CFTR was localised predominantly apically, whereas DeltaF508-CFTR was located
      mainly inside the cell in a region close to the nucleus. Incubation of cells with
      MPB-07 (250 microM) at 37 degrees C for 2 h resulted in pronounced movement of
      DeltaF508-CFTR to the cell periphery, but did not change the localisation of wild
      type CFTR. The results show that DeltaF508-CFTR is mislocalised in native nasal
      epithelial cells and that its distribution is altered in response to the new CFTR
      activator, MPB-07. The findings should lead to development of a rational drug
      treatment for CF patients carrying the DeltaF508 mutation.

PMID- 11845318
TI  - EBIO, an agent causing maintained epithelial chloride secretion by co-ordinate
      actions at both apical and basolateral membranes.
AB  - The effect of 1-ethyl-2-benzimidazolone (EBIO) on electrogenic chloride secretion
      in murine colonic and nasal epithelium was investigated by the short-circuit
      technique. In the colon, EBIO produces a sustained current increase in the
      presence of amiloride, which is sensitive to furosemide. In nasal epithelium EBIO
      causes only a small, transient current increase. Sustained increases in current
      were obtained in response to forskolin in both epithelia. To examine the
      mechanisms by which EBIO increases chloride secretion, the effects on
      intracellular mediators were measured in colonic crypts. There was no effect on
      [Ca(2+)]i but cAMP content was increased, more so in the presence of IBMX,
      indicating a direct effect on adenylate cyclase. In colonic epithelia in which
      the apical surface was permeabilized by nystatin, and the tissue subjected to an
      apical to basolateral K(+) gradient, EBIO caused a current increase that was
      entirely sensitive to charybdotoxin (ChTX). In similarly permeabilized colons Br
      cAMP caused a current increase that was entirely sensitive to 293B. Thus EBIO
      increases chloride secretion in the colon by coordinated actions at both the
      apical and basolateral faces of the cells. These include direct and indirect
      actions on Ca(2+)-sensitive and cAMP-sensitive K(+) channels respectively, and
      indirect actions on the basolateral cotransporter and apical CFTR chloride
      channels via cAMP. In CF colonic epithelia EBIO did not evoke chloride secretion.
      It is not clear why the nasal epithelium responds poorly to EBIO whereas it gives
      a sustained response to the related compound chlorzoxazone.

PMID- 11845317
TI  - The CFTR-mediated protein secretion defect: pharmacological correction.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) mediates secretion
      of mucins and serous proteins. The aim was to correct pharmacologically the CFTR
      defect in protein secretion in airway gland cells and so to correct the viscous
      mucous secretions in cystic fibrosis (CF) airways and lungs. The strategies
      tested included direct activation of CFTR, bypass of CFTR-mediated protein
      secretion and movement of the mutated form of CFTR (DeltaF(508)-CFTR) to the cell
      membrane. Compounds related to 3-isobutyl-1-methylxanthine (IBMX), including a
      selective type-IV phosphodiesterase inhibitor and the adenosine receptor
      antagonists 8-cyclopentyltheophylline (CPT) and 8-cyclopentyl-1,3
      dipropylxanthine (CPX), corrected the defective beta-adrenergic stimulation of
      mucin secretion in CFTR antibody-inhibited submandibular gland cells. CPT also
      corrected lactoferrin secretion in DeltaF(508)/DeltaF(508)-CFTR nasal gland
      cells. The data suggest that correction of CFTR protein secretion activity is not
      mediated by excessive increase in cyclic AMP, involves direct interaction with
      CFTR but does not require increase in CFTR Cl(-) channel activity. Regulated
      glycoprotein secretion was characterised in the airway gland cell line Calu-3 to
      investigate whether a CFTR bypass is present. Studies of DeltaF(508)-CFTR
      trafficking using confocal imaging showed that some DeltaF(508)-CFTR colocalised
      with the apical membrane protein CD59; however a large amount was mislocalised
      within the cell. The results showing pharmacological correction of the defective
      CFTR-mediated protein secretion afford promise for the development of a rational
      drug therapy for CF patients.

PMID- 11845319
TI  - Inhibition of amiloride-sensitive Na(+) absorption by activation of CFTR in mouse
      endometrial epithelium.
AB  - Previous studies have demonstrated amiloride-sensitive Na(+) absorption under
      basal conditions and cystic fibrosis transmembrane conductance regulator (CFTR)
      mediated Cl(-) secretion following neurohormonal stimulation in the mouse
      endometrial epithelium. The present study investigated the inhibition of
      amiloride-sensitive Na(+) absorption accompanying activation of CFTR in the mouse
      endometrium using the short-circuit current ( I(sc)) technique. RT-PCR
      demonstrated the co-expression of CFTR and epithelial Na(+) channels (ENaC) in
      primary cultured mouse endometrial epithelia and cultured endometrial monolayers
      exhibited a basal amiloride-sensitive I(sc) of 5.4 +/- 0.6 microA/cm(2). The
      amiloride-sensitive current fell to 3.1 +/- 0.5 microA/cm(2) after stimulation
      with forskolin. When the possible contribution of Na(+) absorption to the I(sc)
      was eliminated by amiloride (1 microM) or Na(+) replacement, the forskolin
      induced I(sc) was not reduced, but rather increased significantly compared with
      that in the absence of amiloride or in Na(+)-containing solutions ( P < 0.02),
      indicating that the forskolin-induced I(sc) was mediated by Cl(-) secretion,
      portion of which may be masked by concurrent inhibition of basal Na(+) absorption
      if the contribution of Na(+) is not eliminated. When the contribution of Cl(-) to
      the I(sc) was eliminated by diphenylamine 2,2'-dicarboxylic acid (DPC, 2 mM) or
      Cl(-) replacement, forskolin now decreased, rather than increased the I(sc),
      demonstrating the inhibition of Na(+) absorption upon stimulation. Our data
      suggest an interaction between CFTR and ENaC, which may be the underlying
      mechanism for balancing Na(+) absorption and Cl(-) secretion across the mouse
      endometrial epithelium.

PMID- 11845321
TI  - Expression of the androgen receptor and 5 alpha-reductase type 2 in the
      developing human fetal penis and urethra.
AB  - Normal penile development is dependent on testosterone, its conversion via
      steroid 5 alpha-reductase type 2 to dihydrotestosterone, and a functional
      androgen receptor (AR). The goal of this study was to investigate the
      distribution of AR and 5 alpha-reductase type 2 in the developing human fetal
      external genitalia with special emphasis on urethra formation. Twenty fetal
      genital specimens from normal human males (12-20 weeks gestation) were sectioned
      serially and stained by avidin-biotinylated peroxidase complex method with
      antigen retrieval. Stained sections throughout male genital development
      documented the expression of AR and 5 alpha-reductase type 2 in the phallus.
      Between 12 and 14 weeks of gestation, AR was localized to epithelial cells of the
      urethral plate in the glans, the tubular urethra of the penile shaft, and stromal
      tissue surrounding the urethral epithelium. In the fetal penis between 16 and 20
      weeks gestation, the density of AR expression was greatest in urethral epithelial
      cells versus the surrounding stromal tissues. There was a characteristic pattern
      of AR expression in the glandular urethral epithelium between 16 and 20 weeks
      gestation. AR expression was greater along the ventral aspect of the glandular
      urethra than along the dorsal aspect of the urethral epithelium. The expression
      of 5 alpha-reductase type 2 was localized to the stroma surrounding the urethra,
      especially along the urethral seam area in the ventral portion of the remodeling
      urethra. These anatomical studies support the hypothesis that androgens are
      essential for the formation of the ventral portion of the urethra and that
      abnormalities in either the AR or 5 alpha-reductase type 2 can explain the
      occurrence of hypospadias.

PMID- 11845322
TI  - Development of the swimbladder in the European eel ( Anguilla anguilla).
AB  - The swimbladder of the adult eel, Anguilla anguilla, with its bipolar
      countercurrent system, the rete mirabile, is a widely used model for swimbladder
      function, but very little is known about the development of this swimbladder. Our
      histological studies on the developing swimbladder revealed that during
      metamorphosis the swimbladder becomes present as a dorsal outgrowth of the
      esophagus. It is filled with surfactant, and gas was not detected in the
      swimbladder. In the young glass-eel, the epithelial (gas gland) cells of the
      swimbladder are columnar, but do not yet have the typical basolateral labyrinth
      established in adult animals. Few blood vessels are found in the swimbladder
      tissue, and the submucosa is present as a thick layer of connective tissue,
      giving a large diffusion distance between blood vessel and swimbladder lumen.
      Within the next 2 or 3 months of development, gas gland cells develop their
      typical basolateral labyrinth, and the thickness of the submucosa is
      significantly reduced, resulting in a short diffusion distance between blood
      vessels and the swimbladder lumen. The first filling of the swimbladder with gas
      is observed while the gas gland cells are still in a poorly differentiated status
      and it appears unlikely that these cells can accomplish their typical role in gas
      deposition. The presence of small gas bubbles in the swimbladder as well as in
      the ductus pneumaticus at the time of initial swimbladder inflation suggests that
      the swimbladder is filled by air gulping or possibly by taking up gas bubbles
      from the water.

PMID- 11845323
TI  - Integrin-like substrate adhesion in RTG-2 cells, a fibroblastic cell line derived
      from rainbow trout.
AB  - Fluorometric cell attachment assays together with competitive inhibitors of
      adhesion were used to probe for the presence of integrins, a diverse family of
      heterodimeric cell-surface glycoproteins involved in cell-cell and cell
      extracellular matrix adhesion, in the fibroblastic rainbow trout cell line, RTG
      2. The adhesive properties of this cell line were evaluated. RTG-2 cells adhered
      poorly to TC plastic in the absence of serum but as little as 2.5% fetal bovine
      serum allowed over 75% of the cells to attach after 5 h. Surfaces coated with the
      extracellular matrix proteins collagen I, collagen IV, fibrin, fibrinogen, or
      fibronectin were able to support attachment of RTG-2 cells. Adhesion of RTG-2
      cells to fibronectin varied linearly with fibronectin coating densities in the
      range 0 to 65 ng/mm(2). Oligopeptides containing the sequence Arg-Gly-Asp (RGD)
      caused dose-dependent inhibition of adhesion to microtiter plates coated with
      fibrin, fibrinogen, and fibronectin, whereas attachment to collagen I and
      collagen IV was less severely affected. In all cases, peptides containing Arg-Gly
      Glu (RGE) or Asp-Gly-Arg (DGR) sequences caused no reduction of cell attachment.
      Since many integrins mediate adhesion by binding to RGD sequences in their target
      ligands, these results suggest the presence of integrin-like adhesion molecules
      on the surface of RTG-2 cells.

PMID- 11845324
TI  - The expression of scavenger receptor class B, type I (SR-BI) and caveolin-1 in
      parenchymal and nonparenchymal liver cells.
AB  - The liver is the major site of cholesterol synthesis and metabolism, and the only
      substantive route for eliminating blood cholesterol. Scavenger receptor class B,
      type I (SR-BI) has been reported to be responsible for mediating the selective
      uptake of high-density lipoprotein cholesteryl esters (HDL-CE) in liver
      parenchymal cells (PC). We analysed the expression of SR-BI in isolated rat liver
      cells, and found the receptor to be highly expressed in liver PC at both the mRNA
      and protein levels. We also found SR-BI to be expressed in liver endothelial
      cells (LEC) and Kupffer cells (KC). SR-BI has not previously been reported to be
      present in LEC. CD36 mRNA was expressed in all three liver cell types. Since
      caveolin-1 appears to colocalize with SR-BI and CD36 in caveolae of several cell
      lines, the distribution and expression of caveolin-1 in the liver cells were
      investigated. Caveolin-1 was not detected in PC but was found in both LEC and KC.
      This led to the suggestion that caveolin-1 may be more important in the efflux of
      cholesterol than in the selective uptake of cholesterol in the liver.

PMID- 11845325
TI  - Bile canalicular barrier function and expression of tight-junctional molecules in
      rat hepatocytes during common bile duct ligation.
AB  - Tight junctions of hepatocytes form the intercellular barrier between the blood
      circulation and bile flow. We focused on early stages of common bile duct
      ligation to observe changes in tight junctions without the irreversible changes
      seen after lengthy ligation. Common bile ducts of 12-week-old male rats were
      ligated for 6 h because, at this time point, no histological changes were
      observed. Serum bilirubin and bile acid levels began to increase 3 h after
      ligation and were restored to the control level immediately after surgical
      removal of the ligation. To examine the barrier of hapatocytes, horseradish
      peroxidase was injected via the femoral vein, and bile was collected for the
      first 10 min. A four-fold elevation of the secretion and concentration was
      observed in the bile of ligated rats compared with that of control animals. We
      next examined lanthanum permeability by perfusion fixation of the liver. At 6 h
      after ligation, both dilation of the bile canaliculi and partial loss of
      microvilli were commonly observed. There were dense deposits of lanthanum in
      almost all bile canaliculi of ligated rats. In control animals, neither dilation
      of the bile canaliculi nor loss of microvilli was detected, and only 44% of bile
      canaliculi exhibited deposits. An apparent increase of occludin mRNA expression
      was detected in livers after 6 h ligation, whereas the expression of claudin-1, 
      2, and -3 was not influenced by ligation. These results indicate that regulation
      of occludin gene expression is different from that of claudin-1, -2, and -3. The
      early phase of bile stasis employed in this study is thought to be an
      indispensable approach for understanding the precise regulation of tight
      junctions.

PMID- 11845327
TI  - Effects of chemical sympathectomy by means of 6-hydroxydopamine on insulin
      secretion and islet morphology in alloxan-diabetic mice.
AB  - Activation of sympathetic nerves increases circulating glucose and inhibits
      insulin release from the islet beta-cells, which might contribute to stress
      related diabetes. Accordingly, we have shown previously that blockade of
      parasympathetic activity aggravates diabetes in alloxan-treated mice, suggesting
      that unopposed sympathetic activity impairs diabetes. In this study, we tested
      whether elimination of sympathetic nerve activity by chemical sympathectomy with
      6-hydroxydopamine (6-OHDA; 60 mg/kg) ameliorates the diabetogenic effects of
      alloxan (50 mg/kg) in NMRI mice. Mice given alloxan alone developed manifest
      diabetes after 2 days, as indicated by hyperglycemia. The diabetes persisted
      throughout the 35-day study period. Pretreatment with 6-OHDA did not, however,
      affect the glucose levels or the low, 2-min in vivo insulin response to glucose
      (1 g/kg) after alloxan. In situ hybridization at day 35 revealed a significantly
      reduced grain area of insulin-mRNA in the alloxan-treated animals, which was not
      affected by 6-OHDA, and an altered islet architecture, with accumulation of
      glucagon cells in the central portion. Also 6-OHDA alone reduced the insulin mRNA
      area, but this was accompanied by an increase in the total islet area. We
      conclude that, in contrast to cholinergic inhibition, sympathectomy does not
      perturb the development of chemically induced diabetes in mice. Alone, however,
      sympathectomy reduces insulin gene expression and induces increased islet size,
      suggesting that sympathetic nerves are of importance for long-term islet
      function.

PMID- 11845328
TI  - Differentiation of smooth muscle cells in chicken gizzard. Self-catalytic
      mechanism for the production of smooth muscle cells.
AB  - During development of the chicken gizzard, a thick layer of undifferentiated
      cells (mesenchymal cells) is constructed, and the cells differentiate into smooth
      muscle cells or connective tissues. We found that the differentiation of smooth
      muscle cells occurred first near the outer surface of the gizzard and the
      differentiated area spread to the inside of the gizzard. Therefore, we assumed
      that the differentiation of most of the smooth muscle cells in the gizzard is
      induced by differentiated smooth muscle itself. When undifferentiated cells from
      gizzard of 7-day-old embryo (Hamburger and Hamilton's stages 26-27) were cultured
      on a coverglass coated with extract of gizzard that contained differentiated
      smooth muscle cells, the cells attached to the coverglass and differentiated into
      smooth muscle cells. On the other hand, extract of gizzard from 7-day-old embryo
      did not induce the differentiation of smooth muscle cells, though it induced the
      attachment of cells. We found that activity for the differentiation of smooth
      muscle cells appeared when differentiated smooth muscle cells appeared in
      developing gizzard. Gizzard contained higher activity for the differentiation of
      smooth muscle cells than the other tissues. Transforming growth factor-beta (TGF
      beta), which induces the differentiation of vascular smooth muscle cells, did not
      induce the differentiation of smooth muscle cells in gizzard, though extract of
      aorta induced the differentiation of smooth muscle cells in gizzard. The results
      obtained here support evidence that the differentiation of most of the smooth
      muscle cells in gizzard is induced by a self-catalytic mechanism in which
      differentiated smooth muscle itself induces the differentiation of smooth muscle
      cells.

PMID- 11845326
TI  - Over-expression of the glucagon-like peptide-1 receptor on INS-1 cells confers
      autocrine stimulation of insulin gene promoter activity: a strategy for
      production of pancreatic beta-cell lines for use in transplantation.
AB  - To develop transplantable beta-cell lines for the treatment of diabetes mellitus,
      we have taken advantage of the property of INS-1 cells to synthesize and secrete
      not only insulin, but also small quantities of the insulinotropic hormone
      glucagon-like peptide-1 (GLP-1). In INS-1 cells over-expressing the beta-cell GLP
      1 receptor (GLP-1-R), we have shown, by radioimmune assay and bioassay of
      conditioned medium, that an autocrine signaling mechanism of hormone action
      exists whereby self-secreted GLP-1 acts as a competence factor in support of
      insulin gene transcription. INS-1 cells also exhibit insulin gene promoter
      activity, as assayed in cells transfected with a rat insulin gene I promoter
      luciferase construct (RIP1-Luc). The GLP-1-R agonist exendin-4 stimulates RIP1
      Luc activity in a glucose-dependent manner, an effect mediated by endogenous GLP
      1-Rs, and is blocked by the serine/threonine protein kinase inhibitor Ro 31-8220.
      Over-expression of GLP-1-R in transfected INS-1 cells reduces the threshold for
      exendin-4 agonist action, whereas basal RIP1-Luc activity increases 2.5-fold in
      the absence of added agonist. The increase of basal RIP1-Luc activity is a
      consequence of autocrine stimulation by self-secreted GLP-1 and is blocked by
      introduction of (1) an inactivating W39A mutation in the N-terminus ligand
      binding domain of GLP-1-R or (2) mutations in the third cytoplasmic loop that
      prevent G protein coupling. No evidence for constitutive ligand-independent
      signaling properties of the GLP-1-R has been obtained. Over-expression of GLP-1-R
      increases the potency and efficacy of D-glucose as a stimulator of RIP1-Luc.
      Thus, INS-1 cells over-expressing the GLP-1-R recapitulate the incretin hormone
      effect of circulating GLP-1, thereby providing a possible strategy by which beta
      cell lines may be engineered for efficient glucose-dependent insulin biosynthesis
      and secretion.

PMID- 11845329
TI  - Bovine trophoblastic cell differentiation on collagen substrata: formation of
      binucleate cells expressing placental lactogen.
AB  - The differentiation of trophectoderm in ruminants is marked by the appearance of
      binucleate cells in cytotrophoblasts. Binucleate cells are produced by the
      acytokinesis of cytotrophoblasts and undergo endoreduplication. They secrete
      hormones such as placental lactogen, and exhibit migratory behavior to transfer
      their hormones into maternal circulations. In this study, we showed that a bovine
      trophoblastic cell line (BT-1) established from in vitro fertilized blastocysts
      differentiated into binucleate cells on collagen gel. BT-1 had cytotrophoblastic
      epithelial characteristics in that it expressed cytokeratin, E-cadherin and
      interferon-tau. It spontaneously formed multicellular spherical vesicles floating
      in the medium. We cultured these vesicles on type I collagen substrata. Most
      vesicles attached to the collagen substrata, and exhibited cell outgrowth and
      proliferation. We found that after more than 10 days, clusters of binucleate
      cells appeared in the cell colonies on the collagen gel, but not on the collagen
      film. These binucleate cells have features characteristic of those in vivo,
      including an increased nuclear DNA content and the expression of placental
      lactogen. BT-1 is a useful model with which to study trophoblast differentiation
      in ruminants.

PMID- 11845330
TI  - The glucose transport facilitator GLUT8 is predominantly associated with the
      acrosomal region of mature spermatozoa.
AB  - The glucose transporter 8 (GLUT8) is a recently identified member of the family
      of sugar transport facilitators. In human tissues GLUT8 is predominantly
      expressed in testis in a gonadotropin-dependent manner. It is shown here that the
      onset of mRNA synthesis of GLUT8 during the maturation of mouse testis coincides
      with the appearance of mature spermatozoa. Furthermore, immunohistochemistry with
      antiserum against the C-terminus of GLUT8 indicated that the protein was
      associated with spermatozoa within the seminiferous and the epididymal tubules.
      The GLUT8 immunoreactivity was detected within the head of mouse and human
      spermatozoa in the acrosomal region, and appeared to be located at the plasma
      membrane as well as within the cells. This specific expression and localization
      of GLUT8 suggests that the transport facilitator plays a major role in the fuel
      supply of mature spermatozoa, and that it is a potential target for inhibition of
      sperm cell function.

PMID- 11845332
TI  - Neuropeptide Y-immunoreactive neuronal system and colocalization with FMRFamide
      in the optic lobe and peduncle complex of the octopus (Octopus vulgaris).
AB  - The distribution of neuropeptide Y (NPY)-like immunoreactivity and its
      colocalization with FMRFamide were investigated in the optic lobe and peduncle
      complex of the octopus ( Octopus vulgaris) by using immunohistochemical
      techniques. In the optic lobe cortex, NPY-immunoreactive (NPY-IR) fibers were
      observed in the plexiform layer, although no NPY-IR somata were observed in the
      outer or inner granular cell layers. In the optic lobe medulla, NPY-IR somata
      were seen in the cell islands, and abundant NPY-IR varicose fibers were observed
      in the neuropil. Most of the NPY-IR structures in the medulla showed FMRFamide
      like immunoreactivity. In the peduncle lobe, abundant NPY-IR and FMRFamide-IR
      (NPY/FMRF-IR) varicose fibers were seen in the basal zone neuropil of the
      peduncle lobe. In the olfactory lobe, NPY/FMRF-IR varicose fibers were also
      abundant in the neuropil of the three lobules. NPY/FMRF-IR somata, with processes
      running to various neuropils, were scattered in the median and posterior lobules.
      In the optic gland, many NPY/FMRF-IR varicose fibers formed a honeycomb pattern.
      These observations suggest that NPY/FMRF-IR neurons in the optic lobes
      participate in the modulation of visual information and that those in the optic
      gland are involved in the regulation of endocrine function.

PMID- 11845331
TI  - An antibody to recombinant crustacean hyperglycaemic hormone of Nephrops
      norvegicus cross-reacts with neuroendocrine organs of several taxa of
      malacostracan Crustacea.
AB  - The crustacean hyperglycaemic hormones (cHHs) are multifunctional neuropeptides
      that play a central role in the physiology of crustaceans. A partial cDNA coding
      for cHH of the Norway lobster, Nephrops norvegicus, was cloned; this cDNA was
      fused to glutathione- S-transferase (GST) to obtain a recombinant fusion protein
      that was used to raise a rabbit antiserum and to perform a biological assay. The
      specificity of the purified antibody was demonstrated by means of Western
      blotting. To validate the specificity of the purified antibody to the cHH of N.
      norvegicus and its cross-reactivity with other species, we performed standard
      immunocytochemistry of the eyestalk on: (1) paraffin sections of the decapod
      species N. norvegicus, Munida rugosa and Astacus leptodactylus and of the
      stomatopod Squilla mantis; (2) semithin resin sections of N. norvegicus and
      Palaemon elegans; (3) ultrathin sections of N. norvegicus sinus gland
      (transmission electron microscopy studies). The pattern of immunoreactivity shown
      by N. norvegicus eyestalk sections conforms to distribution, relative amount and
      ultrastructural features of cHH-containing neurons and nerve endings as reported
      in the previous literature. In all the crustacean species examined, the antibody
      marks precisely the X organ-sinus gland complex and unspecific staining is
      completely lacking. In addition, its specific cross-reaction by
      immunoprecipitation depletes shrimp eyestalk extract of hyperglycaemic activity
      in an in vivo bioassay. The results obtained show a cHH-specific molecular
      recognition despite the fact that the species tested belong to systematic groups
      increasingly remote in the phylogenetic tree. The antibody could be used for
      advancing our knowledge on cHH activity in a variety of crustacean species, e.g.
      for monitoring reproductive and stress conditions.

PMID- 11845333
TI  - Juvenile-hormone-dependent interaction of actin and spectrin is crucial for
      polymorphic differentiation of the larval honey bee ovary.
AB  - Programmed cell death in the worker ovary of Apis mellifera reduces the number of
      ovarioles during metamorphosis from 150-200 primordia to less than 10. In
      contrast, practically all ovarioles in the ovary of queens survive to the adult
      stage. The correct formation and persistence of polyfusomes has been suggested as
      a critical factor for ovariole survival. We have analyzed the developmental
      dynamics of F-actin and alpha-spectrin in fusomes of queen and worker larvae, and
      in juvenile-hormone-treated worker larvae. Small fusomes containing actin and
      spectrin can be detected in the ovaries of fourth instar larvae in both castes.
      After molting to the fifth instar, the actin-spectrin association persists in the
      enlarged fusomes of queen ovarioles. In workers, actin dissociates from the
      fusomal and cortical alpha-spectrin. Coinciding with the appearance of apoptosis
      markers, large agglomerates of actin are detectable in worker ovarioles.
      Treatment of fourth-instar worker larvae with juvenile hormone rescues ovarioles
      from apoptosis and maintains the actin-spectrin association. Juvenile-hormone
      dependent actin-spectrin interaction is thus one of the earliest steps in the
      differentiation of a polymorphic ovary. Plasticity in ovariole numbers as a
      result of hormone-dependent fusome formation may be a more widespread phenomenon
      in insects, extending beyond caste polymorphism in highly eusocial Hymenoptera.

PMID- 11845335
TI  - [Does weather modify headaches? An empirical evaluation of bio-weather
      categorization].
AB  - BACKGROUND: Headache patients frequently refer to the weather as a triggering
      factor for their headaches. Apart from a literature review, we tested empirically
      the generally used classification of weather epochs into a so called bio-weather
      categorization. METHOD: Headache diary data (frequency, duration, intensity) of
      98 patients in a headache trial were correlated with the concurrent bio-weather
      classification. RESULTS: Correlations were small and significant only for the
      summer-half of the year (contingency coefficients between 0.04 and 0.06). The
      classification of certain types of weather as headache prone as used in the
      current bio-weather classification could only partly be verified. CONCLUSION:
      There is a clear but small correlation between headache and weather. More, and
      more fine-grained, studies are warranted, especially for identifying those
      patients at risk for weather prone headaches. Clinically more important is the
      weather as a source of causal attributions.

PMID- 11845336
TI  - [Gabapentin in the treatment of chronic intractable pain].
AB  - INTRODUCTION: Gabapentin has been shown to reduce pain associated with diabetic
      neuropathia and postherpetic neuralgia. To date it is not known, whether
      gabapentin is generally effective in other types of pain. It was therefore the
      aim to study gabapentin in patients suffering from intractable pain with respect
      to efficacy, predictive factors and side effects. METHODS: Retrospective analysis
      of the data sheet of pretreated patients suffering from intractable pain and
      treated with gabapentin as a third line drug at a university pain clinic. Pain
      intensity (visual analogue scale, VAS 0 -10 cm), pain characteristics, diagnosis,
      pre- and co-treatment, and side effects were assessed. Response to treatment was
      defined as a 50% reduction in pain or a pain intensity of VAS </= 3. RESULTS: 99
      patients were included. Approximately half the patients (n = 49) responded to
      gabapentin. Patients suffering from neuropathic pain showed a higher response
      rate (60%) compared to patients with muscle-sceletal pain (35%). Allodynia was
      twice as high in the responders (35%) compared to the non-responders (18%) before
      treatment. No serious side effects were reported. CONCLUSION: Gabapentin was
      effective in approximately 50% of pretreated patients with intractable pain.
      Neuropathic pain responded better than pain of other origine. Allodynia may be a
      predictive factor for a positive treatment effect.

PMID- 11845337
TI  - [Results of early mobilisation of acute whiplash injuries].
AB  - BACKGROUND: Diagnostic evaluation and therapeutic management of acute neck pain
      after whiplash is a frequent but unsolved clinical problem. Long-lasting symptoms
      and disability are common. Former studies proposed beneficial effects of
      physiotherapy in the early management of whiplash injury. The purpose of this
      study was to assess the effects of early active mobilization versus standard
      treatment with a soft cervical collar. METHODS: Between August 1997 and February
      2000 a prospective randomized clinical trial with a total of 168 patients was
      performed. Of these patients 81 (31 male, 50 female; average age 28,78 years)
      were randomly assigned to the standard therapy group, which received a soft
      cervical collar, and 87 (31 male, 56 female; average age 29,62 years) to the
      early mobilization group, treated by physiotherapy. Study participants documented
      pain and disability twice (baseline and six week follow-up) during a one week
      period by diary, using numeric rating scales ranging from 0 to 10. RESULTS: The
      initial mean pain intensity (4,75) reported by the standard therapy group was
      similar to disability (4,76). There were no significant differences to initial
      pain (4,50) and disability (4,39) reported by the early mobilization group. The
      mean pain intensity reported by the standard therapy group after 6 weeks was 2,66
      and disability was 2,40. The mean pain intensity indicated by physiotherapy group
      was 1,44 and mean disability was 1,29. The differences between the groups were
      both significant. CONCLUSIONS: Early mobilization is superior to the standard
      therapy regarding pain intensity and disability. We conclude that mobilization
      should be recommended as the new adequate standard-therapy in the acute
      management of whiplash injury.

PMID- 11845338
TI  - [Interventions for improvement of primary care in patients with low back pain:
      how effective are advice to primary care physicians on therapies and a multimodal
      therapy program arising out of cooperation of outpatient health care
      structures?].
AB  - BACKGROUND: Treatment for chronic low back pain in primary care has a poor
      quality outcome. There is evidence that multimodal therapy is the most successful
      approach to its management. We tried to evaluate whether giving primary care
      physicians evidence-based recommendations on therapy of chronic back pain or
      directly implementing a multimodal program would improve the outcome of patients
      with low back pain treated in primary care. METHODS: In the first phase,
      physicians were asked to document the course of patients suffering from low back
      pain of at least 4 weeks' duration with no decrease in intensity, noting pain
      intensity before and after 6 months of conventional, nonsurgical treatments. In
      the present, second, phase of the study, recommendations issued by the Medicines
      Committee of the German Medical Profession and the U.S. Agency for Health Care
      Policy and Research for the management of back pain were presented to doctors in
      printed form and at conferences. In parallel with this, a multimodal program for
      the treatment of chronic low back pain (4 h/day for 20 days: medical training
      therapy, cognitive-behavioral therapy, physiotherapy, and patient education) was
      organized in a private health-oriented sports center in cooperation with three
      private physiotherapy practices, and a psychologist and a pain specialist from
      the outpatient pain clinic at the University Hospital in Erlangen. We examined
      how physicians changed the therapy and how effective it was, the latter as
      reflected in the mean sum value of the percent pre- to posttreatment changes in
      pain intensity, how much pain interfered with daily living, depressivity, and
      quality of life. Data after interventions were compared with baseline data from
      the first phase. RESULTS: Data relating to 36 patients following treatment by 14
      primary care physicians who had been given information about therapy
      recommendations and to 51 patients who had participated in the multimodal therapy
      program were compared with baseline data recorded in 157 patients.
      Recommendations changed neither the therapy preferred by primary care physicians
      nor the quality of outcome of conventional treatment. In contrast, the multimodal
      program of therapy for chronic low back pain improved the outcome significantly
      more than conventional therapy (mean improvement in general outcome score 22 vs.
      7%, respectively, compared with baseline data; P<0.001). CONCLUSIONS: Giving
      primary care physicians information on the therapy recommended for treatment of
      low back pain does not lead to any change in physicians' preferred therapy.
      Multimodal programs for treatment of chronic low back pain should be organized
      locally, with existing health care providers joining forces to improve the
      quality of outcome in chronic low back pain managed in primary care.

PMID- 11845339
TI  - [Measuring the willingness of chronic pain patients to change pain management
      behavior - a study on the transtheoretical model].
AB  - RESEARCH QUESTION: The transtheoretical model (TTM) describes the willingness of
      behavior change as a process characterized by six stages: precontemplation,
      contemplation, preparation, action, maintenance, and termination. This study
      investigates the possibility to apply the TTM to the treatment of chronic pain
      patients. The main goal is the development of items for a self-administered
      instrument, which documents the willingness to use cognitive-behavioral methods
      for pain management independently. With this instrument a treatment can be
      assigned according to the patient's motivation in order to improve outcomes of
      pain management programs. METHODS: Based on TTM theory 56 items were developed
      and adminstered to a sample of 118 chronic pain patients, who were recruited via
      different facilities for pain therapy. Item- and factor analysis were conducted
      for determining psychometrical attributes of items and latent scales. RESULTS:
      Analyses resulted in four consistent scales and accordingly four distinctive
      stages: precontemplation, preparation, action, and maintenance, which showed
      sufficiently high indices of homogeneity and discriminant validity. The
      relationships between scale scores and sociodemographic and pain related
      variables proved to be in accordance to the theory. CONCLUSIONS: The results show
      transferability of the TTM to pain management in general. Two stages,
      contemplation and termination, could not be identified yet. Mainly termination
      seems not to be existent in the context of pain management. A further study
      should confirm these findings before therapeutical interventions can be assigned
      more specifically by the motivational preparedness.

PMID- 11845340
TI  - [Application of guidelines for the treatment of headache and cancer pain by
      private practitioners].
AB  - In a regional pain management network in Cologne, sponsored by the German
      Ministry of Health, structures of outpatient pain treatment in general practice
      and the adherence to pain management guidelines were examined. The 3-year project
      was divided into a 1-year observational period to analyze the present state of
      outpatient pain management followed by a 2-year period of interventions such as
      consultations and educational training programs in pain treatment. Eighty
      physicians with different specializations working in general practice took part
      in the network. The knowledge of and adherence to the guidelines for the
      treatment of headache and cancer pain were examined by questionnaire surveys and
      six simulated patient cases. These investigations were performed yearly from 1997
      to 2000. The adherence to the guidelines for the treatment of headache and cancer
      pain by the physicians participating in the network was low. The levels achieved
      for simulated cases of headache were higher than for cancer pain. The results of
      simulated patient cases from the beginning and the end of the project were
      available for comparison for 28 physicians. Evaluation of the physicians'
      assessment of the simulated patient cases increased only fractionally and was not
      significant in headache patients (median change of 0.67) and cancer pain patients
      (median change of 0.17). The network interventions resulted in a slight
      improvement in the knowledge of and attitudes to the treatment of headache and
      cancer pain as judged by simulated patient cases. This improvement, however, did
      not reach statistical significance. The small number of physicians answering at
      the beginning and at the end of the project made it difficult to draw a general
      conclusion on whether the interventions had led to an improvement in outpatient
      pain management in a larger group of physicians.

PMID- 11845341
TI  - [Treatment of idiopathic headache in childhood - recommendations of the German
      Migraine and Headache Society (DMKG)].
AB  - According to the principles of evidence-based medicine, the controlled studies on
      the treatment of idiopathic headache in childhood have been analysed and compiled
      to treatment recommendations. For the acute treatment of migraine attacks or
      tension-type headache, ibuprofen (10 mg per kg body weight) or acetaminophen (15
      mg per kg body weight) are recommended with highest evidence, intranasal
      sumatriptan (10 to 20 mg) can be given as second choice. For the prophylaxis of
      migraine, betablockers (propranolol and metoprolol), flunarizine, and valproic
      acid are recommended. Flunarizine is the drug of first choice in the treatment of
      migraine-related disorders. No controlled studies are available for the treatment
      of further headache types. First line methods for the non-drug treatment of
      headache in childhood are relaxation therapies, biofeedback, and specific
      training schedules.

PMID- 11845343
TI  - [D.G.S.S. President's corner].

PMID- 11845342
TI  - [Dealing with migraines].

PMID- 11845344
TI  - Reliability of the transepicondylar line as a parameter of femoral axial
      alignment.
AB  - The purpose of this research was to determine the significance of the
      transepicondylar line as a parameter of femoral axial alignment. Standing full
      length X-ray films of 124 knees of 91 patients (63 women, 28 men) with
      osteoarthritis, rheumatoid arthritis, or osteonecrosis were used in this study,
      in which the lateral angles formed by the femoral anatomical axis intersecting
      with the transepicondylar line (angle a'), horizontal line (angle b'), and
      femoral condylar line (angle r') were measured. The mean value of angle b' in
      knees with neutral alignment was significantly smaller than that in knees with
      varus alignment, and significantly larger than that in knees with valgus
      alignment; no significant difference was found in angle a'. Also, there was no
      significant difference in angle a' among the patients with osteoarthritis,
      rheumatoid arthritis, and osteonecrosis. These findings suggest that the
      transepicondylar line, which is a stable reference of femoral rotation, is also a
      very reliable parameter of axial alignment of the femur. In the future design of
      extramedullary guiding for total knee arthroplasty, the transepicondylar line may
      play an important role as a parameter for proper and accurate implant setting.

PMID- 11845345
TI  - Gait analysis of spastic walking in patients with cervical compressive
      myelopathy.
AB  - To assess neurological status and to evaluate the effect of surgical
      decompression in patients with cervical myelopathy, we performed computerized
      gait analysis in 24 patients with cervical compressive myelopathy who showed
      spastic walking. Gait analysis was repeated during neurological follow-up that
      averaged 32.4 months. The gait pattern in patients with severe myelopathy was
      characterized by hyperextension of the knee in the stance phase without plantar
      flexion of the ankle in the swing phase, significantly reduced walking speed and
      step length, prolonged stance phase duration and decreased single-stance phase
      duration, and increased step width. The angle of flexion of the knee joint in the
      stance phase was significantly correlated with the Japanese Orthopaedic
      Association (JOA) score. Postoperative neurological improvement was associated
      with increased walking speed and decreased extension angle of the knee joint
      (single-stance phase and swing phase). Postoperatively, 12 patients had
      normalized extension of the knee in stance phase and their walking speed,
      cadence, stance phase duration, and single-stance phase duration, as well as step
      length and width, showed nonsignificant differences from these parameters in
      healthy controls. Our results show that kinesiological gait analysis is
      clinically useful for the functional assessment of the severity of spastic
      walking in cervical myelopathy.

PMID- 11845346
TI  - Prediction of neurologic outcome in patients with spinal cord injury by using
      hyperbaric oxygen therapy.
AB  - The effectiveness of hyperbaric oxygen therapy (HBO) in predicting neurological
      recovery in patients with spinal cord injury was evaluated. HBO has been used to
      treat spinal cord injury, but HBO does not appear to greatly alter the
      neurological outcome. This is the first report of the use of HBO as a diagnostic
      tool to evaluate neurological recovery after spinal cord injury. The study group
      consisted of 22 patients, aged 21-73 years, with spinal cord injuries. The effect
      of HBO was evaluated on admission and categorized as one of four grades
      (excellent, good, fair, or poor). The neurological status was evaluated on
      admission and at the time of follow-up, according to Frankel grade and the
      American Spinal Injury Association (ASIA) motor score. Correlations between the
      HBO effect and Frankel grade recovery and correlations between the HBO effect and
      recovery rate of the ASIA motor score were evaluated. The recovery in Frankel
      grade from admission to the final follow-up became better as the effectiveness of
      HBO increased (r = 0.445; P = 0.0414). The Frankel grade (r = 0.036; P = 0.871)
      and ASIA motor score (r = 0.029; P = 0.893) on admission did not correlate with
      the recovery in Frankel grade. There was a significant correlation between the
      HBO effect and the recovery rate of the ASIA motor score (r = 0.586; P = 0.0072),
      but this correlation was weaker than that for the ASIA motor score on admission
      (r = 0.752; P = 0.0006). We conclude that HBO can be employed to assess the
      status of spinal cord function recovery after spinal cord injury.

PMID- 11845347
TI  - A radiographic analysis of anterior-posterior translation in total knee
      arthroplasty.
AB  - We performed radiological analyses to examine the relationship between the knee
      flexion angle and the anteroposterior translation movement relative to the
      prosthetic components (NexGen type) after total knee arthroplasty (TKA). Cruciate
      retaining (CR) type TKA was performed in 12 knees with osteoarthritis (OA) and 9
      knees with rheumatoid arthritis (RA) in which no posterior cruciate ligament
      (PCL) tear was present. Posterior-stabilized (PS) type TKA was performed in 7 OA
      knees and 7 RA knees in which the PCL was defective or resected. The measurements
      were performed according to the methods of Watanabe. The contact point ratio
      (percentage) was calculated by dividing the distance to the contact point (CP;
      the closest point of contact between the femoral and tibial components) by the
      antero-posterior length of the tibial component. After TKA, the CP at full
      extension was positioned more posteriorly than in the normal knee both under
      weight-bearing and non-weight-bearing conditions. Except for the RA knees in the
      PS group, the CP translated anteriorly in the early phase of flexion and then
      posteriorly. Under weight-bearing conditions, the posterior translation occurred
      earlier and was smaller in magnitude. For RA knees in the PS group, the CP moved
      gently posteriorly right from the beginning.

PMID- 11845348
TI  - Postoperative changes on functional mapping of the motor cortex in patients with
      brachial plexus injury: comparative study of magnetoencephalography and
      functional magnetic resonance imaging.
AB  - Using magnetoencephalography (MEG) and functional magnetic resonance imaging (f
      MRI), we investigated the areas of the cerebral cortex that were activated when
      patients with brachial plexus injuries performed elbow flexion, a motion re
      acquired through nerve transfer surgery. In all patients, elbow flexion on the
      operated side and on the unaffected side led to the activation of an area in the
      motor cortex, with these areas being located almost symmetrically on either side
      of the sagittal midline. These findings suggest that the activity center for the
      transferred intercostal nerves shifted to the motor cortex for the elbow, from
      the original intercostal nerve site.

PMID- 11845349
TI  - Regional specificity in degenerative changes in finger joints: an anatomical
      study using cadavers of the elderly.
AB  - Rehabilitation therapists and orthopedists regard degenerative changes (DCs) of
      the articular cartilage or osteoarthritis in the finger joint as the major
      factors that interfere with normal grasp and pinch. However, previous research
      has concentrated on DCs in the carpometacarpal joint (CM) of the thumb. The
      present study revealed some general tendencies concerning the occurrence of DCs:
      (1) distal joint dominance between joints in a thumb or finger; (2) distal
      surface dominance in a joint; (3) radioulnar dominance in a joint; and (4) fifth
      finger specificity (i.e., high incidences of both DCs and osteophytes). Moreover,
      according to our evaluation of multiple and solitary occurrences (i.e., how many
      segments carried DCs) we consider that DCs in the radioulnar segments advance not
      only to the complementary surface (i.e., mirror-image lesion formation) but also
      to other adjacent segments in the early stage before progression to cartilage
      defects occurs in the primarily affected segment. In addition, osteophytes were
      not associated with the cartilage defect in the adjacent segment, but, rather,
      occurred at opposite or distant segments in the joint. These results are
      discussed in relation to lateral pinch and precision grasping, with special
      reference to the hypothetical stress on these movements in the finger joint.

PMID- 11845350
TI  - A cell line with multinucleated giant cell formation established from a human
      giant cell tumor of tendon sheath--preliminary report.
AB  - We first established a cell line with unique giant cell formation properties from
      a human giant cell tumor of tendon sheath (GCTTS) arising in the right ankle of a
      7-year-old girl. The specimen for cell culture taken from the tumor was
      heterotransplanted into the back of a BALB/c (nu/nu) nude mouse. An in-vitro cell
      line was established from a tumor that grew after this heterotransplantation.
      Only mononuclear cells were observed in the primary culture, and these remained
      constant in growth. Multinucleated giant cells appeared at passage 3 and were
      constantly observed thereafter. The fusion of mononuclear cells into giant cells
      was verified by light and phase-contrast microscopy. This cell line was confirmed
      to be derived from a human by karyotype analysis and DNA fingerprinting. The cell
      doubling time was 150 h. This cell line should be useful for studies of the
      mechanism of multinucleation in giant cell tumors.

PMID- 11845351
TI  - Influence of chronic inflammation in peripheral target tissue on recovery of
      crushed nerve injury.
AB  - An experimental study was performed to investigate the influence of chronic
      inflammation in peripheral target tissue on recovery of the sciatic nerve after
      crush injury. Thirty-four male Wistar rats, weighing 300-370 g were used. The
      sciatic nerve was crushed unilaterally with an aneurysm clip (250 gf; holding
      force; 5 min). One week before the operation, chronic inflammation, localized in
      the tibiotarsal joint of one hind limb, was produced by the intraarticular
      injection of complete Freund's adjuvant. The animals were divided into five
      groups, as follows: CIA (crush injury with ipsilateral arthritis), CCA (crush
      injury with contralateral arthritis), C (crush injury without arthritis), A (sham
      operation and ipsilateral arthritis), and S (sham operation without arthritis).
      Specimens for histological examination were taken from the nerve at a site 5 mm
      distal to the crush injury 4 weeks postoperatively. Histological study showed
      that the diameters of the axons in group CIA were significantly smaller than
      those in group CCA and those in group C. No significant differences were observed
      between group CCA and group C. In conclusion, peripheral nerve recovery after
      crush injury was suppressed by chronic inflammation in peripheral target tissue.

PMID- 11845352
TI  - Tumor growth potential after tumoral and instrumental contamination: an in-vivo
      comparative study of T-saw, Gigli saw, and scalpel.
AB  - In the field of spinal tumors, intralesional tumor cutting is sometimes
      inevitable. The purpose of this study was to compare the potential for tumor
      growth after intralesional cutting by T-saw, Gigli saw, and scalpel. Tumors,
      prepared by the subcutaneous injection of human HT 1080 fibrosarcoma cells in
      nude mice, were harvested and cut with a T-saw, Gigli saw, or scalpel. A 3-cm
      wound was created in the skin on the back in another group of nude mice. The cut
      surface of the tumor was rubbed for 10 s against the subcutaneous tissue in this
      second group of nude mice. In the same manner, the instrument used for tumor
      cutting was rubbed against the subcutaneous tissue in the 3-cm wound in the back
      of a third group of nude mice for 10 s. Other instruments used for tumor cutting
      were immediately washed in culture medium, and the total number of tumor cells
      was counted. Tumor blocks and single-cell suspensions prepared from tumor tissues
      of the same weight were inoculated and injected into a fourth group of nude mice.
      The incidence of tumor growth after the rubbing of the subcutaneous tissue with
      the tumor surface cut with a T-saw, Gigli saw, and scalpel was 16.7%, 50.0%, and
      33.3%, respectively. The corresponding figures after the rubbing of the
      subcutaneous tissue with a T-saw, Gigli saw, and scalpel was 16.7%, 33.3%, and
      33.3%, respectively. The mean numbers of tumor cells attached to the T-saw, Gigli
      saw, and scalpel were 1.88 x 105, 5.02 x 105, and 4.92 x 105, respectively.
      Finally, the incidence of tumor growth after the inoculation of tumor blocks and
      single-cell suspensions was 100% and 77.8%, respectively. These findings show
      that tumor recurrence is less likely after intralesional tumor cutting with a T
      saw than after such cutting with a Gigli saw or scalpel.

PMID- 11845353
TI  - Ankle arthrodesis and tibial lengthening for congenital sensory neuropathy with
      anhidrosis.
AB  - This report describes a patient with congenital sensory neuropathy with
      anhidrosis (CSNA) with destructive arthropathy of the left ankle joint that was
      treated with ankle arthrodesis and tibial lengthening, using an Ilizarov external
      fixator. The fusion at the ankle joint was successful, but, at the lengthening
      site, loosening of the apparatus occurred and formation and maturation of the
      distracted callus were delayed. Intramedullary nailing was used after the removal
      of the external fixator, and a low-intensity ultrasound device was employed,
      after which the distracted callus matured gradually. During the maturation
      period, the patient's dysplastic right hip joint was destroyed, without the
      occurrence of any severe symptoms. Distraction osteogenesis in patients with CSNA
      may lead to good results if rigid fixation, nonweight-bearing (i.e., adequate
      rest), and appropriate biological stimulation can be employed.

PMID- 11845354
TI  - Hip-shelf procedure in the treatment of osteonecrosis of the transpositioned
      acetabulum after rotational acetabular osteotomy.
AB  - Necrosis of the transpositioned acetabulum after rotational acetabular osteotomy
      (RAO) is a major complication characteristic of this procedure. This
      complication, although rare, has been thought difficult to treat. We report a
      patient with acetabular osteonecrosis and subsequent collapse after RAO that was
      effectively treated with a shelf operation, providing satisfactory remodeling of
      the hip joint. A 16-year-old female had undergone RAO for the treatment of
      developmental acetabular dysplasia. Postoperative radiography showed that the
      osteotomized acetabular fragment was unusually thin, and that the osteotome
      entered the hip joint during the surgery. Five months after the RAO, X-rays
      revealed significant collapse of the transpositioned acetabulum, and femoral head
      subluxation caused by postoperative osteonecrosis. Seven months after the RAO,
      the patient underwent a hip-shelf procedure. The remaining acetabular fragment
      was used in this procedure, according to the Spitzy method. Seven years after the
      second operation, favorable remodeling of the hip joint was observed; however,
      early osteoarthritic changes, including slight joint space narrowing, bone
      sclerosis of the new acetabulum, and bone cysts within the femoral head, were
      seen.

PMID- 11845355
TI  - Simultaneous ipsilateral fractures of distal and proximal ends of the radius.
AB  - We treated a patient with a rare combination of ipsilateral fractures of the
      distal and proximal ends of the radius. A woman aged 52 years had simultaneous
      fractures of the distal and proximal ends of the radius (radial head and neck)
      after she fell from a high place. The fracture of the radial head was treated by
      open fixation with a cancellous bone screw, and the fractured distal end of the
      radius was treated by bone graft, with the subsequent application of an external
      fixator. At the 1-year follow up, the patient had minor residual limitation of
      forearm pronation and elbow joint extension, but she had no pain on movement, and
      had a good result based on Cooney's score (90 points).

PMID- 11845356
TI  - Resorption of synthetic porous hydroxyapatite and replacement by newly formed
      bone.
AB  - Synthetic porous hydroxyapatite (HA) is commonly used as a bone substitute for
      bone defects which, previously, would have been treated by autogenous bone
      grafting. HA has been thought to be a nonbiodegradable material that remains as
      it is implanted. However, after long-term follow-up, some authors report that the
      margin of implanted HA blocks or granules is absorbed, suggesting that HA is
      biodegradable. We experienced a patient in whom synthetic HA blocks implanted in
      a bone defect of the ilium after the harvesting of full-thickness bone for
      grafting were extensively absorbed and replaced by newly formed bone 6 years and
      7 months after the implantation. Therefore, we conclude that HA is biodegradable.
      Sintering temperature, porosity, and pore diameter seem to influence the
      biodegradability of HA.

PMID- 11845357
TI  - Biomechanics and repair of articular cartilage.
AB  - The most important function of the joints relies on excellent lubrication and the
      uniform distribution of impact loads onto the underlying bones, together with
      damping effects. In most joint disorders, as the lesion is limited to the joint
      surface, it becomes necessary to repair the joint surface. In this article,
      repair with an artificial composite osteochondral device (COD) is reported, as is
      biological resurfacing with cultured chondrocytes. The COD consists of polyvinyl
      alcohol (PVA) hydrogel as artificial cartilage and titanium fiber mesh (TFM) as
      porous artificial bone. PVA solution was impregnated into the pores of TFM by
      injection molding, and these two materials were bound together by a gelling
      process to create the COD. The key problem, i.e., to attain quick and firm
      attachment to the underlying bone, was addressed by creating this COD, in which
      the TFM interface allows not only firm attachment of the PVA gel but also strong
      attachment to the joint surface through bony ingrowth. For the purpose of
      simulating partial hemiarthroplasty for the femoral head, 30 COD prostheses were
      implanted into canine femoral heads. Histological findings of the acetabular
      cartilage and synovial membrane, as well as findings of attachment of the
      prosthesis to bone, were examined for an 18-month period after the operation. No
      particular pathological changes in acetabular cartilage were found, and firm
      attachment of the devices to bone was confirmed. These results indicate that the
      COD could be a very promising joint repair material.

PMID- 11845358
TI  - Cartilaginous lesions of bone.
AB  - Cartilaginous lesions of the skeleton are very unusual. It is extremely important
      to correlate the roentgenographic features, the clinical features, and the
      histological features to arrive at a definite diagnosis. Most cartilaginous
      lesions are benign or of low-grade malignancy. However, there are some subtypes
      of chondrosarcoma that behave in a highly aggressive fashion.

PMID- 11845360
TI  - Feasibility study to detect ovarian cancer micrometastases by fluorescence
      photodetection.

PMID- 11845361
TI  - The control of fire hazard during cutaneous laser therapy.
AB  - This article reviews the literature on fire hazard relating to the laser
      treatment of cutaneous conditions and collates recommended precautions. Further
      suggestions are added.

PMID- 11845362
TI  - Recent advances in laser therapy for the treatment of cutaneous vascular
      disorders.
AB  - The use of lasers for the treatment of cutaneous vascular disorders has expanded
      rapidly since its inception in the early 1960s. The flashlamp-pumped pulsed
      tunable dye laser (PDL), which is the best laser system for the treatment of port
      wine stains (PWS), is based on the premise of selective photothermolysis. Recent
      literature demonstrates enhanced selective photothermolysis by modifying the PDL
      to include a longer pulse width, a longer wavelength and higher energy fluences
      through the use of dynamic cooling. Multiple pulse laser irradiation, a new
      innovative method, shows promising preliminary results in eradicating
      hypertrophic PWS. In the treatment of capillary haemangiomas, previous
      uncontrolled studies suggest benefit with early PDL therapy but a recent
      randomised controlled trial does not support this claim. Mixed haemangiomas
      respond poorly to PDL treatment, uncomplicated tumours are best left to involute
      spontaneously whilst life/organ-threatening lesions require early active
      intervention. The efficacy of lasers in the treatment of telangiectatic leg veins
      (TLV) remains controversial. The literature revealed many conflicting claims.
      Larger and properly controlled studies are necessary to better define the role of
      lasers in the treatment of TLV.

PMID- 11845363
TI  - Subjects' dissimilarity in the analysis of laser-tissue dose-response
      experiments: a potential cause for puzzling results.
AB  - The in vivo dose-response laser-tissue experiment is usually performed on several
      subjects, each exposed several times at different tissue sites. The collected
      data are then unified into a single statistical batch and analysed under the
      tacit assumption that the tolerances of all the subjects are similar. However, if
      this assumption is incorrect the data unification may lead to very biased
      results. This study reanalyses a raw data set measured by the US Army Medical
      Research Detachment Walter Reed Army Institute of Research (USAMRD-WRAIR), which
      was used to study the influence of the laser wavelength on the energy threshold
      of retinal injury. The USAMRD-WRAIR report reveals a significant variation of
      threshold with small changes in wavelength. Despite an extensive study, performed
      by the USAMRD-WRAIR researchers, which included possible lasers variations, many
      aspects of experimental technique and biological absorption properties of the
      eye, a cause for the threshold variation was not found. Our current results
      suggest that unaccounted specimen's dissimilarity might be the cause for this
      unclear threshold variations.

PMID- 11845364
TI  - Changed skin blood perfusion in the fingertip following acupuncture needle
      introduction as evaluated by laser Doppler perfusion imaging.
AB  - Rapidly repeated imaging of the left middle fingertip skin blood perfusion was
      performed in 51 healthy volunteers (mean age +/- SD: 25.3 +/- 7.6 years) prior
      to, immediately after and in the early reperfusion phase following introduction
      of an acupuncture needle at the Neiguan point (Pe. 6) and at a placebo point
      respectively, using a Laser Doppler Perfusion Imager (LDPI). The average skin
      perfusion of the fingertip was calculated for each image and used as an indicator
      of the microvascular response to the acupuncture needle introduction. The results
      of this randomised, placebo-controlled, cross-over study showed significant
      differences (p < or = 0.001) in the immediate skin blood perfusion response when
      needling is performed in an acupuncture point (Neiguan) and a placebo point, with
      a more pronounced reduction in skin blood perfusion when needling the acupuncture
      point. In the early reperfusion phase, however, a substantial increase in skin
      perfusion was observed that amounted to about 18% of the level prior to needle
      introduction, irrespective of the site of needle application. In a single
      individual it was demonstrated that the vasodilatation following needling in the
      acupuncture point persisted for a more extended time period. These results
      suggest that the LDPI technology may be useful in visualising and quantifying the
      peripheral vascular effects of acupuncture on the microcirculation.

PMID- 11845365
TI  - Laser treatment of erythema and telangiectasia associated with rosacea.
AB  - The response of rosacea-associated erythema and telangiectasia to treatment with
      the pulsed tunable dye laser (PDL) was evaluated in 12 patients. Improvements in
      erythema, telangiectasia, flushing, the physician's and the patient's perception
      of overall severity, treatment tolerability, and the adverse side effects were
      examined. With the sole exception of the patient's assessment of overall severity
      we have found highly significant improvements in all other parameters evaluated,
      with excellent tolerance of treatment. We therefore conclude that the PDL is a
      safe and effective treatment for the erythemato-telangiectatic component of
      rosacea.

PMID- 11845366
TI  - Thermally induced irreversible conformational changes in collagen probed by
      optical second harmonic generation and laser-induced fluorescence.
AB  - Irreversible thermal conformational changes induced to collagen have been studied
      by optical methods. More specifically, second harmonic generation (SHG) from
      incident nanosecond Ng:YAG 1064 nm radiation and laser-induced fluorescence by
      337 nm, pulsed nanosecond nitrogen laser excitation, at 405, 410 and 415 nm
      emission wavelengths were registered at eight temperatures (40 degrees, 50
      degrees, 55 degrees, 60 degrees, 65 degrees, 70 degrees, 75 degrees and 80
      degrees C) and normalised with respect to the corresponding values at the ambient
      temperature of 30 degrees C. The heating protocol used in this work, was selected
      to monitor only permanent changes reflecting in the optical properties of the
      samples under investigation. In this context, the SHG, directly related to the
      collagen fibril population in triple helix conformation, indicated on
      irreversible phase transition around 64 degrees C. On the other hand fluorescence
      related to the destruction of cross-linked chromophores in collagen, some of
      which are related to the triple helix tertiary structure, also indicated a
      permanent phase transition around 63 degrees C. These results are in agreement
      with previous results from studies with differential scanning calorimetry.
      However SHG and fluorescence, being non-invasive optical methods are expected to
      have a significant impact in the fields of laser ablative surgery and laser
      tissue welding.

PMID- 11845367
TI  - Photodynamic therapy of activated and resting lymphocytes and its antioxidant
      adaptive response.
AB  - In this work we have studied the effects of ALA-mediated photodynamic therapy
      (PDT) on resting and mitogen-activated murine splenic lymphocytes, evaluating its
      impact on cell viability. We have also characterised the stress response,
      measuring the levels of antioxidant enzymes. A 2h exposure to ALA produced 50%
      lethality upon irradiation of activated cells with 2.1J/cm2. The decrease in cell
      survival with increasing time exposure to ALA, correlated well with the higher
      porphyrin accumulation. In resting lymphocytes, in spite of the low amount of
      porphyrins formed during 2h incubation with ALA, 40% of the cells died after
      irradiation, this response was not further increased when higher amounts of
      porphyrins were synthesised. Superoxide dismutase was impaired by light treatment
      independently of ALA exposure in activated lymphocytes and, to a lesser extent,
      in resting lymphocytes. PDT induced an antioxidant adaptive response in activated
      cells 19 h after irradiation, reflected as a net increase in GSHPx activity and a
      slight reversion of the catalase (CAT) activity already impaired by light
      treatment. PDT treatment of activated cells also produced a diminution in the
      GSH/GSSG ratio. Only activated cells are capable of developing an antioxidant
      adaptive response to PDT treatment.

PMID- 11845368
TI  - Photodynamic therapy (PDT) for oesophageal dysplasia and early carcinoma with
      mTHPC (m-tetrahydroxyphenyl chlorin): a preliminary study.
AB  - Barrett's oesophagus is a premalignant condition in which stratified squamous
      type mucosa of the normal oesophagus is replaced by specialised intestinal type
      columnar mucosa. Oesophageal resection was previously considered to be the
      treatment of choice for high-grade dysplasia or superficial carcinoma arising in
      this columnar-lined mucosa. We treated four patients with Barrett's oesophagus
      and high-grade dysplasia, and one patient with superficial oesophageal carcinoma
      with photodynamic therapy (PDT) using an argon-pumped dye laser light (652 nm).
      PDT was also delivered using a xenon arc lamp (Paterson lamp, light 652 nm +/- 15
      nm) in two patients with Barrett's oesophagus and high-grade dysplasia. mTHPC (m
      tetrahydroxyphenyl chlorin) 0.15 mg/kg was used as a photosensitiser in all the
      patients. We have been able to demonstrate the elimination of columnar-lined
      oesophageal mucosa, reduction in the length of the Barrett's segment or
      downgrading of the dysplasia in all of the patients. There is no evidence of
      recurrence in the patient who had oesophageal carcinoma, at 27 months follow-up.
      We conclude that mTHPC is useful as a photosensitiser for PDT in the management
      of Barrett's oesophagus with high-grade dysplasia or superficial carcinoma and
      the Paterson lamp is a potential alternative light source for PDT.

PMID- 11845369
TI  - Efficacy of low power laser therapy in fibromyalgia: a single-blind, placebo
      controlled trial.
AB  - Low energy lasers are widely used to treat a variety of musculoskeletal
      conditions including fibromyalgia, despite the lack of scientific evidence to
      support its efficacy. A randomised, single-blind, placebo-controlled study was
      conducted to evaluate the efficacy of low-energy laser therapy in 40 female
      patients with fibromyalgia. Patients with fibromyalgia were randomly allocated to
      active (Ga-As) laser or placebo laser treatment daily for two weeks except
      weekends. Both the laser and placebo laser groups were evaluated for the
      improvement in pain, number of tender points, skinfold tenderness, stiffness,
      sleep disturbance, fatigue, and muscular spasm. In both groups, significant
      improvements were achieved in all parameters (p<0.05) except sleep disturbance,
      fatigue and skinfold tenderness in the placebo laser group (p>0.05). It was found
      that there was no significant difference between the two groups with respect to
      all parameters before therapy whereas a significant difference was observed in
      parameters as pain, muscle spasm, morning stiffness and tender point numbers in
      favour of laser group after therapy (p<0.05). None of the participants reported
      any side effects. Our study suggests that laser therapy is effective on pain,
      muscle spasm, morning stiffness, and total tender point number in fibromyalgia
      and suggests that this therapy method is a safe and effective way of treatment in
      the cases with fibromyalgia.

PMID- 11845370
TI  - Acute electrophysiological effect of pulsed gallium-arsenide low-energy laser
      irradiation on isolated frog sciatic nerve.
AB  - We evaluated the acute electrophysiological effects of low-energy pulsed laser
      irradiation on isolated frog sciatic nerve measured by extracellular recording
      technique. A pulsed gallium-arsenide (GaAs) laser (wavelength: 904 nm, pulse
      duration 220 ns, peak power per pulse: 27W, spot size: 0.28 cm(2), total applied
      energy density: 0.005-2.5J/cm(2)) was used for the experiment. Sixty isolated
      nerves were divided into six groups (n=10), each of which received a different
      laser dose. In each group, action potentials were recorded before laser
      irradiation which served as the control data. The extracellular action potentials
      were recorded for each combination of 1, 3, 5, 7, 10, 13 and 15 minutes of
      irradiation time and 4, 8, 16, 32, 64 and 128 repetition frequency by using a
      BIOPAC MP 100 Acquisition System Version 3.5.7 (Santa Barbara, USA). Action
      potential amplitude, area, duration and conduction velocity were measured.
      Statistical evaluation was performed using repeated measures variance analysis by
      SPSS 9.0. There were no statistically significant differences for action
      potential amplitude, area and conduction velocity among the laser groups and
      control data (p>0.05). The study showed that low-energy GaAs irradiation at 4-128
      Hz repetition frequencies administered for irradiation times of 1-15 min
      generates no effect on action potential amplitude, area, duration and conduction
      velocity in isolated frog sciatic nerve.

PMID- 11845374
TI  - [Separation of the airways: historical aspects].
AB  - Techniques to separate the airways to both lungs were employed in the laboratory
      by renowned physiologists like Pfluger and C. Bernard to study gas exchange.
      Pfluger's catheter, as used by Wolffberg in 1871 in the dog, essentially
      constituted an early example of endobronchial single lumen tube, and was to be
      the first airway separator introduced into man by Loewy and v. Schrotter in 1905
      in experiments on circulation. As a variation of this device the carinal hook
      made ist appearance used by Hess in 1912 in rabbits. While the endobronchial
      catheters afforded airtight access to only one lung at a time for concomitantly
      studying ventilation in both lungs, a short tracheal cannula was combined with
      one introduced into the left main bronchus by Head in 1889, constituting as it
      were the prototype of double lumen (DL) tubes applicable to rabbits and turtles
      even. Werigo described 1892 a coaxial DL-tracheostomy cannula for dogs which
      construction principle was adopted in the first DL-bronchoscope used in man. In
      lung surgery during the 30s and 40s the ventilated lung was prevented from
      drowning by pus or secretions from the lung under surgery by sealing off ist main
      bronchus, either by endobronchial intubation or by a bronchial blocker inserted
      alongside the endotracheal tube. This principle gave rise to sophisticated
      devices, from the fixed combination of tube and blocker to the present-day tube
      housing a movable blocker. Remarkably, DL-intubation in its proper sense then was
      performed in bronchospirometry only. This technique was introduced by Jacobaeus
      upon suggestion of Liljestrand when dissatisfied with the restriction to
      sequential spirometry by customary bronchoscopic catheterization, relying on
      Frenckner's ingenious DL-bronchoscope. Rubber DL-tubes were developed by Gebauer
      1939 and Zavod 1940 exclusively with bronchospirometry in mind, even E. Carlens
      primarily constructed his tube to improve this procedure. After its usage in over
      100 bronchospirometries it was introduced for the first time in November 1949 for
      its familiar purpose: the resection of a tuberculous abscess in the right upper
      lobe. Once introduced into thoracic anaesthesia, the DL-principle so far fostered
      a wide variety of tube designs.

PMID- 11845375
TI  - [Prophylaxis of Postoperative Nausea and Vomiting FollowingGynaecological
      Laparoscopy].
AB  - OBJECTIVE: Compared to other procedures, gynaecological laparoscopies are
      followed rather frequently by postoperative nausea and vomiting (PONV).
      Therefore, we investigated the prophylactic antiemetic efficacy of metoclopramide
      and droperidol under general anaesthesia with isoflurane (part 1). Given the
      rather unsatisfying results of this monoprophylaxis we examined the effects of a
      quintuple prophylaxis in this setting (part 2). METHODS: Part 1: Following
      ethical committee approval and written informed consent 120 patients scheduled
      for elective gynaecological laparoscopy were allocated prospectively, randomly
      and observer-blinded to the following groups: group P (placebo): 2 ml NaCl 0.9 %,
      group D: 2.5 mg droperidol, group M: 10 mg metoclopramide. Part 2: Subsequently
      50 patients scheduled for elective gynaecological laparoscopy and bearing a
      minimum risk of 25 % to experience postoperative vomiting were allocated
      prospectively and blinded to the observers to a quintuple prophylaxis group:
      group X: 10 mg metoclopramide, 2.5 mg droperidol, 12.5 mg dolasetron, 62.5 mg
      dimenhydrinate, 8mg dexamethasone. Part 1 and 2: Anaesthesia was induced with
      fentanyl, etomidate and succinycholine and maintained with isoflurane/N2O,
      fentanyl and cisatracurium. The antiemetics were applied intravenously 20 min
      prior to end of surgery. RESULTS: Within the first 24 h postoperatively vomiting
      occurred more frequently in group P (44 %) compared to group D (21 %, p = 0.046)
      and group M (33 %, n. s.). Nausea also occurred more frequently in group P (61 %)
      compared to group D (24 %, p = 0.003) and group M (48 %, n. s.). Intensity of
      nausea was reduced both in group D and group M compared to group P (p = 0.03).
      Likewise the requirements for antiemetics as a rescue medication were reduced in
      group D (p = 0.02) and group M (p = 0.047) compared to group P. In group X no
      patient suffered from postoperative vomiting, no patient required a rescue
      antiemetic. CONCLUSIONS: Whereas droperidol provides a reliable antiemetic
      effect, the prophylactic effect of metoclopramide is rather uncertain. Therefore,
      further studies regarding a dose response-relationship for metoclopramide are
      deemed necessary. Since a monoprophylaxis with droperidol or metoclopramide
      failed to attain a satisfying PONV-prophylaxis in patients at high risk for PONV,
      the quintuple antiemetic combination might be an effective and safe solution.

PMID- 11845377
TI  - Oxygen-benefit and risks.

PMID- 11845376
TI  - [Effects of Repetitive Exposure to Hyperbaric Oxygen (HBO) on Leukocyte
      Function].
AB  - OBJECTIVE: Despite favourable clinical data on the successful use of hyperbaric
      oxygen (HBO), only limited investigations have been carried out to date regarding
      the influence of hyperoxia on leukocyte function. In a murine model, CD4+ T-cell
      population remained unchanged after repeated HBO exposure, however CD8+ cells
      were found to be increased. The aim of this study was to investigate whether
      repetitive exposure to hyperoxia would affect human monocyte and lymphocyte
      function. METHODS: Methods: After Ethics Committee approval the effects of
      elevated partial oxygen pressure were studied in the course of a ten-day HBO
      therapy (2.5 atmospheres absolute over a daily period of 90 min). Monocytes and
      lymphocytes of 30 patients with acute hearing loss were determined by flow
      cytometry before, throughout and after HBO therapy using monoclonal antibodies to
      CD3, CD4, CD8, CD14, CD25, CD45 and HLA-DR. Statistical analysis was made by
      ANOVA (analysis of variance). RESULTS: The relative percentage of CD3+, CD4+,
      CD8+, CD25+, CD14+, and HLA-DR+ cells remained unchanged during the course of and
      after HBO therapy. CONCLUSIONS: We conclude that repetitive exposure to hyperoxia
      does not influence human monocyte and lymphocyte functions in contrast to
      experimental data.

PMID- 11845379
TI  - [Oxygen - a vital dangerous substance].

PMID- 11845380
TI  - [Pulmonal oxygen reservoir-physiology and clinical benefit].

PMID- 11845381
TI  - [Hyperbaric oxygen therapy--options and limitations].

PMID- 11845382
TI  - [Risks concerning oxygen in laser surgery].

PMID- 11845383
TI  - [Avoidance of hypoxemia during one lung ventilation].

PMID- 11845384
TI  - [Reduction by half of wound infection rate after colon surgery through increase
      of inspirational oxygen concentration from 30 % to 80 %].

PMID- 11845385
TI  - [BSE - A cause for Creutzfeldt- Jakob disease? ].

PMID- 11845386
TI  - [Epidemiology and clinical symptomatology of Creutzfeldt-Jakob disease].
AB  - OBJECTIVE: Analogous to prospective studies in other countries, prevalance and
      symptoms of sporadic Creutzfeldt-Jakob disease (CJD) were recorded in order to
      assess irregularities in the incidence of the disease in Germany since the onset
      of bovine spongioform encephalopathy (BSE). PATIENTS AND METHODS: SInce 1993 all
      suspected case of CJD reported in the Federal Republic of Germany have been
      analysed by a unified schema and classified by standardised criteria. In addition
      to voluntary reporting two other systems were accessed: (1) compulsory reporting
      to the Robert Koch Institute via the appropriate Health Department and (2) cause
      of death statistics of the Federal Office of Statistics. RESULTS: Between June
      1993 and May 2001, a total of 1247 patients with suspected CJD, obtained by the
      angle quotation mark, rightStudy of the epidemiology and early diagnosis of human
      spongioform encephalopathiesangle quotation mark, left at Gottingen University,
      were examined. The suspected disease was confirmed by autopsy in 404 cases, the
      diagnosis of probable CJD was made in 369 cases on the basis of clinical data and
      additional investigation. At the beginning of the Gottingen Study in 1993 the
      incidence in Germany was 0.7 per mill. population, while in the year 2000 it had
      risen to 1.3 per mill. population. Corresponding increases in the number of cases
      since 1993 have been noted also by the Robert Koch Institute and the Federal
      Office of Statistics. CONCLUSIONS: The increased incidence can be explained
      primarily by a decrease in previously unknown cases. Concerted action as part of
      the Gottingen Study has increased the cooperation of associated clinics. In
      addition to sporadic cases of CJD, genetic and, more rarely, iatrogenic forms
      have been seen in Germany. But no cases of new variant CJD have been reported so
      far.

PMID- 11845387
TI  - [Clinically atypical CJD: diagnostic relevance of cerebrospinal fluid markers and
      molecular genetic analysis?].
AB  - HISTORY AND CLINICAL FINDINGS: A 66-year-old woman with known remitting
      depressive episodes was admitted to a psychiatric hospital where a severe major
      depression was diagnosed. The patient failed to respond to SSRI medication. In
      addition, she developed a pronounced speech disturbance and gait ataxia.
      Therefore she was referred to the department of neurology 5 months after disease
      onset. She presented with a predominant cerebellar syndrome. Because of a severe
      dysarthria testing of cognitive functions were impossible. INVESTIGATIONS: EEG
      revealed a general slowing of the basic activity. Periodic sharp wave complexes
      were not seen during the entire disease course. Cerebrospinal fluid analysis
      (CSF) was normal with regard to cell count and blood-csf-barrier function. 14- 3
      3 proteins were detected in CSF, and CSF levels of tau-protein and neuron
      specific enolase were strongly elevated. A point mutation was detected at codon
      196 (E196K) of the prion proteine gene. In addition, codon 129 was found
      homozygous for valine. TREATMENT AND COURSE: During the following 10 weeks the
      patient developed pyramidal and extrapyramidal signs, myoclonus and akinetic
      mutism. Complications were decubital ulcers and infections of the urinary tract.
      The myoclonus slightly regressed following treatment with benzodiazepines. The
      patient died 9 months after disease onset. CONCLUSION: A rapid disease course and
      typical changes of surrogate markers in CSF may support the in-vivo diagnosis of
      CJD despite incomplete clinical criteria (e. g. lack of dementia). In such cases,
      detection of mutations by molecular genetic analysis is of importance to further
      support the diagnosis of CJD.

PMID- 11845388
TI  - [Early and differential diagnosis of Creutzfeldt-Jakob disease].

PMID- 11845389
TI  - [Immunity against prions?].

PMID- 11845390
TI  - [New variant Creutzfeldt-Jakob disease].

PMID- 11845391
TI  - [BSE and Creutzfeldt-Jakob disease. Implication on health politics in Germany and
      Europe].

PMID- 11845392
TI  - [25 theses against the assertion that BSE and vCJD are orally transmissible
      infectious diseases and endanger human health].

PMID- 11845393
TI  - [BSE and variant CJD: about the difficulties to establish a new pathogenetic
      principle].

PMID- 11845395
TI  - [Hearing disorders in children with Down's syndrome].
AB  - Among 4947 children in an outpatients unit for hearing disorders 102 children
      with Down's syndrome were seen and checked for hearing disorders. 57 had hearing
      deficiencies, 50 (88 %) conductive hearing loss, 4 (7 %) combined and 3 (5 %) a
      sensory neural hearing loss. Compared to other publications the number of very
      young children was very high. 32 patients under two years of age had a hearing
      disorder. The results underline the necessity of early diagnosis and follow up
      also in children with normal reactions during the first presentation. Early
      diagnosis enables early treatment, conservative, surgical or fitting with hearing
      aids, especially important in the rehabilitation of these children. Hearing aids
      may be given temporarily imploring communication during the development of the
      child.

PMID- 11845396
TI  - [Acquired fibrotic atresia of the external auditory canal].
AB  - BACKGROUND: There are very few communications on this pathologic entity, which is
      also called "postinflammatory medial meatal fibrosis" (PIMMF), its etiology and
      the adequate therapy. Apparently the cause is a chronic inflammation (or chronic
      ekzema) of the medial part of the external meatus or also a long-lasting otorrhea
      in chronic otitis media. The stratified epithelium of the eardrum and of the
      adjacent bony meatus is destroyed and replaced by fibrotic tissue. The lateral
      part of the auditory canal remains open and has the form of the finger of a
      glove, it may contain granulations, but often it is lined with a smooth
      stratified epithelium. A severe conductive hearing loss is the result of this
      anomaly. PATIENTS: During the last 10 years we operated on 46 patients (52 ears)
      for this pathology: after retroauricular opening, which allows the best control
      of the anterior tympanomeatal angle, the fibrotic tissue was removed keeping the
      lamina propria intact. The bony canal was widened, if necessary. The eardrum and
      the bony canal were covered with split skin graft from the retroauricular region,
      then the canal filled with an antibiotic package for 3 weeks. RESULTS: Underneath
      the fibrotic tissue we detected 3 cholesteatomata of the annular region, so it is
      important to remember, that the atresia may also cover a dangerous pathology. 6
      times a second operation was necessary, besides that, we observed 14
      recurrencies. All other patients had a wide epithelialized ear canal, their
      conductive hearing loss disappeared, and the results were stable over several
      years. Bacteriological and histological examinations were not helpful to clear up
      the etiology of this disease. CONCLUSIONS: Surgery is the treatment of choice of
      the acquired atresia of the external meatus. We suppose that in these patients a
      individual disposition causes the formation of this excessive fibrosis, which has
      some similarity with keloid formation.

PMID- 11845397
TI  - [The enlargement of the meatal entrance in canal-wall-down operations].
AB  - BACKGROUND: The canal-wall-down operation may narrow the meatal entrance.
      METHODS: By means of excision of skin from the cavum conchae and conchal
      cartilage an adequate-sized meatus can be created. RESULTS: 17 children were
      treated in case of cholesteatoma with canal-wall-down operation and metoplasty.
      The meatal entrance was sufficiently enlarged in all patients. CONCLUSIONS: The
      presented metoplasty supplies good functional and cosmetic results.

PMID- 11845398
TI  - [Reconstruction of hypopharynx after pharyngolaryngectomy with U-shaped radial
      forearm flap].
AB  - BACKGROUND: After pharyngolaryngectomy reconstructive procedures of the upper
      digestive tract are necessary. Since the introduction of microvascular tissue
      transplantation jejunal loops proved to be a versatile transplant. Nevertheless
      it has some disadvantages as i. e. the increased donor morbidity, a rather high
      sensitivity to hypoxia and the tendency of shrinkage and formation of stenosis.
      METHOD: We perform the reconstruction of the hypopharynx with the radial forearm
      flap. The fasciocutaneous flap is harvested on the radial artery in a size of 12
      x 6 cm in average and is sutured U-shaped paramedian to the prevertebral fascia.
      In addition the posterior wall of the oesophagus and the oropharynx have to be
      adapted to the prevertebral fascia. RESULTS: Between 1997 and 2001 we performed
      these reconstructions in 20 patients. In one case we found a complete flap
      necrosis, which required secondary reconstruction with a pectoralis major flap.
      In 2 patients we saw a stenosis at the junction to the oesophagus, which was
      treated by revision surgery and bougienage. In 18 patients swallowing was
      regular. 6 patients were able to learn oesophageal speech. CONCLUSION: The radial
      forearm flap in its U-shaped transposition to the prevertebral fascia represents
      a functionally good reconstructive procedure for the hypopharynx.

PMID- 11845399
TI  - [20 years' experience with extracorporal septoplasty].
AB  - Even today the difficult septum presents a surgical problem. A severe septum
      deformity is caused mostly by an accident or is seen in patients with
      malformation like CLP-deformity. It is characterized by a massive deformation in
      all levels with a consecutive blocking of one or both airways. Such severe septal
      deformities cannot be corrected properly by classical septoplasty techniques.
      Therefore we suggest an extracorporal septoplasty, where the whole septum is
      taken out and by different techniques a new septal plate is reconstructed and
      then replanted. From 1981 to 2001 we operated 1855 patients and improved this
      method constantly, especially the safe septal fixation after replantation. Follow
      ups showed that even in severe deformities a revision rate of only 5 %
      respectively 7 % was found. Therefore we conclude the extracorporal septoplasty
      with its refinements can also be recommended also to the less experienced
      rhinosurgeon.

PMID- 11845400
TI  - [The sentinel node concept in head and neck squamous cell carcinoma--a critical
      analysis in 100 patients].
AB  - BACKGROUND: The value of Sentinel Node (SN) concept is a current issue in
      clinical oncology. Few investigations deal with SN biopsy in head and neck
      squamous cell carcinomas (HNSCC). For this reason the SN concept was investigated
      based on the results of the so far largest group of 100 patients. METHOD: Three
      groups of patients were investigated. Group 1: In 30 patients (6 x oral cavity,
      24 x oropharynx) a dynamic lymphoscintigraphy was performed. Group 2: 60
      previously untreated patients (12 x oral cavity, 23 x oropharynx, 16 x larynx, 9
      x hypopharynx); neck lymph node status on ultrasound imaging: 39 x N0, 5 x N1, 16
      x N2, intraoperative identification of the SN during neck dissection (ND)
      accomplished according to the extent of assumed lymphogenic metastatic spread;
      postoperative comparison of the histological result of the SN with the neck
      dissection specimen. Group 3: 10 previously treated patients (1 x oral cavity, 5
      x oropharynx, 1 x larynx, 3 x hypopharynx) in whom an intraoperative SN biopsy
      was performed. RESULTS: Group 1: In 20/30 patients a cervical lymph drainage
      could be visualized on dynamic lymphscintigraphy and an activity enrichment above
      the mean metastatic region could be identified transcutaneously. Group 2: In 34
      patients the tumorfree SN1 reflected the regional lymph node status. In 9
      patients an isolated tumor metastasis (pN1) was found in the intraoperatively
      identified SN1 and in a further patient in the SN2 (pN1). CONCLUSION: The results
      of SN biopsy are encouraging in cases of clinical N0-necks. Nevertheless the data
      demonstrates that extensive investigations followed by a critical analysis of the
      results are required. The presented results suggest that the value of the SN
      concept seems to be of minor importance in cases of advanced lymphogenic
      metastatic spread.

PMID- 11845401
TI  - [Current therapeutical management, new antibiotics and treatment of Pseudomonas
      aeruginosa in bacterial ENT-infections].
AB  - In bacterial infections of the sinuses and the middle ear Streptococcus
      pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Staphylococcus
      aureus are most frequently isolated, whereas in tonsillopharyngitis Streptococcus
      pyogenes is the most important pathogen. S. aureus is found in up to 40 % in
      acute and chronic sinusitis and causes severe complications in otitis media,
      therefore antibiotics used as empirical initial treatment should also be
      effective against this pathogen. To decrease duration of illness and to avoid
      serious complications antibiotic treatment of bacterial ENT-infections is
      necessary. The new ketolides and the third and fourth generation quinolones are
      very effective and the second generation cephalosporins like cefuroxime axetil
      have proven excellent clinical and bacteriological efficacy in numerous clinical
      trials combined with an excellent resistance pattern over the years. Efficacy of
      short course therapy (5 days) in sinusitis and tonsillopharyngitis has been
      proven in clinical trials and is cost saving. In more severe infections treated
      in hospital sequential i. v./oral therapy offers pharmaco-economical benefits.
      Both regimen demonstrate cost savings while maintaining high clinical efficacy.
      In more severe infections like otitis externa diffusa, otitis externa maligna,
      otitis media chronica and perichondritis Pseudomonas aeruginosa is a dangerous
      pathogen that has to be covered by initial antibiotic treatment. Ciprofloxacin
      and Ceftazidime are widely used and effective. Ciprofloxacin resistance has
      increased, while Ceftazidime susceptibility is unchanged (> 90 %). A dose
      reduction study with ceftazidime in severe ENT-infections showed equivocal
      efficacy between 3 x 1 g and 3 x 2 g daily that offers a cost benefit of 50 %.

PMID- 11845402
TI  - [Diagnosis and therapy of diseases of the larynx in the history of medicine].
AB  - BACKGROUND: FIRST CLINICAL APPROACHES. Bozzini in Frankfurt, Germany, in 1806
      constructed the first endoscope, by which cavities of the human body could be
      inspected through a tube, but he was hardly able to demonstrate the larynx. His
      attempts were continued by Avery in London in 1840 with special view to the
      larynx but were not successful. Babington in London in 1829 constructed a
      glottiscope combining an angled mirror with a depressor for the tongue. He will
      probably have been able to inspect the larynx in some cases, but he did not
      continue these studies. Liston in London in 1837 reported that he had seen
      pathological findings of the larynx in a few cases by means of an angled mirror.
      FIELD OF RESEARCH: PHYSIOLOGY OF THE VOICE. Ferrein in Paris in 1741 was the
      first to carry out experiments on human larynges. These were continued in a
      systematic way by the physiologist Johannes Muller in Berlin in 1837 analysing
      the movements of the vocal cords. Manuel Garcia, a Spanish singing teacher, first
      in Paris, later in London, had studied the anatomy of the larynx very carefully,
      especially the muscle fibres. In 1855 he succeeded in inspecting his own larynx
      by means of an angled mirror and observed and described the movements of the
      vocal cords in great detail. At first his discovery did not arouse great
      attention, but later he was honoured very much as the inventor of laryngoscopy.
      SYNTHESIS OF PHYSIOLOGY AND CLINIC: Vienna 1857/58: The physiologist Carl Ludwig
      was preparing the second edition of his textbook on physiology, in which he
      extensively referred to Garcia's technique of laryngoscopy. His collegue Ernst
      Brucke was working on the physiological basis of phonetics. Johann Nepomuk
      Czermak, also a physiologist, was a guest of Brucke's and Ludwig's in Vienna
      during the winter 1857/58 and was inspired by the research work of his hosts. The
      neurologist Ludwig Turck had made experiments to visualize the human larynx in
      bodies and patients without knowing of Garcia's achievements. Since he used sun
      light only he had interrupted his studies in autumn 1857 and had lent his
      instrument, a mirror similar to that used by Garcia, to Czermak. Czermak used
      artificial light and the perforated concave mirror that had recently been
      introduced into ophthalmology. He was at once successful in inspecting his own
      larynx. He reported on this as early as March 1858 without informing Turck,
      although he mentioned him and the mirror that he had lent him. There was a public
      dispute about the priority between Turck and Czermak which drew wide attention to
      the invention of laryngoscopy which now was readily introduced in practical
      medicine forming the new discipline of laryngology. This development is
      delineated with many anecdotal details.

PMID- 11845403
TI  - [The yellow-nail-syndrome].
AB  - Two cases of yellow nail syndrome were reported with a review of the literature.
      The yellow nail syndrome is a rare disease, typically characterized by the trias
      of scleronychia (yellow nails), peripherical lymphostasis and pleural effusions.
      In 25 % the cases are accompanied by sinusitis. In the beginning of the disease
      the affects of the sinus are the main problem. For this reason otolaryngologists
      are often the first medical doctors faced with the treatment of yellow nail
      syndrome.

PMID- 11845404
TI  - [The monthly interesting case--case no. 51. Tuberculoid mastoiditis on the right
      side].

PMID- 11845405
TI  - [Prognostic factors in primary radiochemo-therapy in advanced head and neck
      tumours with specific reference to the tumour cell cycle components and tumour
      oxygenation].

PMID- 11845406
TI  - The structure of diversity within New World mitochondrial DNA haplogroups:
      implications for the prehistory of North America.
AB  - The mitochondrial DNA haplogroups and hypervariable segment I (HVSI) sequences of
      1,612 and 395 Native North Americans, respectively, were analyzed to identify
      major prehistoric population events in North America. Gene maps and spatial
      autocorrelation analyses suggest that populations with high frequencies of
      haplogroups A, B, and X experienced prehistoric population expansions in the
      North, Southwest, and Great Lakes region, respectively. Haplotype networks
      showing high levels of reticulation and high frequencies of nodal haplotypes
      support these results. The haplotype networks suggest the existence of additional
      founding lineages within haplogroups B and C; however, because of the
      hypervariability exhibited by the HVSI data set, similar haplotypes exhibited in
      Asia and America could be due to convergence rather than common ancestry. The
      hypervariability and reticulation preclude the use of estimates of genetic
      diversity within haplogroups to argue for the number of migrations to the
      Americas.

PMID- 11845407
TI  - Mutations in a novel factor, glomulin, are responsible for glomuvenous
      malformations ("glomangiomas").
AB  - Glomuvenous malformations (GVMs) are cutaneous venous lesions characterized by
      the presence of smooth-muscle--like glomus cells in the media surrounding
      distended vascular lumens. We have shown that heritable GVMs link to a 4--6-cM
      region in chromosome 1p21-22. We also identified linkage disequilibrium that
      allowed a narrowing of this VMGLOM locus to 1.48 Mb. Herein, we report the
      identification of the mutated gene, glomulin, localized on the basis of the YAC
      and PAC maps. An incomplete cDNA sequence for glomulin had previously been
      designated "FAP48," for "FKBP-associated protein of 48 kD." The complete cDNA for
      glomulin contains an open reading frame of 1,785 nt encoding a predicted protein
      of 68 kD. The gene consists of 19 exons in which we identified 14 different
      germline mutations in patients with GVM. In addition, we found a somatic "second
      hit" mutation in affected tissue of a patient with an inherited genomic deletion.
      Since all but one of the mutations result in premature stop codons, and since the
      localized nature of the lesions could be explained by Knudson's two-hit model,
      GVMs are likely caused by complete loss of function of glomulin. The abnormal
      phenotype of vascular smooth-muscle cells (VSMCs) in GVMs suggests that glomulin
      plays an important role in differentiation of these cells--and, thereby, in
      vascular morphogenesis--especially in cutaneous veins.

PMID- 11845408
TI  - An autosomal recessive form of bilateral frontoparietal polymicrogyria maps to
      chromosome 16q12.2-21.
AB  - Polymicrogyria is a cerebral cortical malformation that is grossly characterized
      by excessive cortical folding and microscopically characterized by abnormal
      cortical layering. Although polymicrogyria appears to have one or more genetic
      causes, no polymicrogyria loci have been identified. Here we describe the
      clinical and radiographic features of a new genetic form of polymicrogyria and
      localize the responsible gene. We studied two consanguineous Palestinian
      pedigrees with an autosomal recessive form of bilateral frontoparietal
      polymicrogyria (BFPP), using linkage analysis. Five affected children had
      moderate-to-severe mental retardation, developmental delay, and esotropia, and
      four of the five affected children developed seizures. Brain magnetic-resonance
      imaging revealed polymicrogyria that was most prominent in the frontal and
      parietal lobes but involved other cortical areas as well. A genomewide linkage
      screen revealed a single locus that was identical by descent in affected children
      in both families and showed a single disease-associated haplotype, suggesting a
      common founder mutation. The locus for BFPP maps to chromosome 16q12.2-21, with a
      minimal interval of 17 cM. For D16S514, the maximal pooled two-point LOD score
      was 3.98, and the maximal multipoint LOD score was 4.57. This study provides the
      first genetic evidence that BFPP is an autosomal recessive disorder and serves as
      a starting point for the identification of the responsible gene.

PMID- 11845409
TI  - Traces of early Eurasians in the Mansi of northwest Siberia revealed by
      mitochondrial DNA analysis.
AB  - The mitochondrial DNA (mtDNA) of 98 Mansi, an ancient group (formerly known as
      "Vogul") of Uralic-speaking fishers and hunters on the eastern slope of the
      northern Ural Mountains, were analyzed for sequence variants by restriction
      fragment--length polymorphism analysis, control-region sequencing, and sequencing
      of additional informative sites in the coding region. Although 63.3% of the mtDNA
      detected in the Mansi falls into western Eurasian lineages (e.g., haplogroups UK,
      TJ, and HV), the remaining 36.7% encompass a subset of eastern Eurasian lineages
      (e.g., haplogroups A, C, D, F, G, and M). Among the western Eurasian lineages,
      subhaplogroup U4 was found at a remarkable frequency of 16.3%, along with
      lineages U5, U7, and J2. This suggests that the aboriginal populations residing
      immediately to the east of the Ural Mountains may encompass remnants of the early
      Upper Paleolithic expansion from the Middle East/southeastern Europe. The added
      presence of eastern Eurasian mtDNA lineages in the Mansi introduces the
      possibilities that proto-Eurasians encompassed a range of macrohaplogroup M and N
      lineages that subsequently became geographically distributed and that the
      Paleolithic expansion may have reached this part of Siberia before it split into
      western and eastern human groups.

PMID- 11845410
TI  - Carrier screening for mucolipidosis type IV in the American Ashkenazi Jewish
      population.
AB  - Mutations in the MCOLN1 gene cause mucolipidosis type IV (MLIV), a severely
      debilitating, autosomal recessive, lysosomal storage disorder. Approximately 80%
      of patients with MLIV are of Ashkenazi Jewish (AJ) descent, and two mutations,
      IVS3-2A-->G and 511del6434, account for >95% of the mutant alleles in this
      population. To determine the carrier frequencies of these two mutations, 2,029
      anonymous, unrelated, unaffected AJ individuals from the greater New York
      metropolitan area were screened. A multiplex PCR method coupled with allele
      specific oligonucleotide hybridization was developed, to enable large-scale
      screening. The frequencies of the IVS3-2A-->G and 511del6434 mutations were 0.54%
      and 0.25%, respectively, for a combined carrier frequency of 0.79%, or 1 in 127
      individuals (95% CI 0.40%-1.17%). The addition of both AJ mutations causing this
      neurodegenerative disorder should be considered for prenatal carrier screening in
      this population.

PMID- 11845412
TI  - Sibling recurrence risk ratio as a measure of genetic effect: caveat emptor!

PMID- 11845413
TI  - The pain of surgery: the agony of undermedication.

PMID- 11845411
TI  - Ethnic-difference markers for use in mapping by admixture linkage disequilibrium.
AB  - Mapping by admixture linkage disequilibrium (MALD) is a potentially powerful
      technique for the mapping of complex genetic diseases. The practical requirements
      of this method include (a) a set of markers spanning the genome that have large
      allele-frequency differences between the parental ethnicities contributing to the
      admixed population and (b) an understanding of the extent of admixture in the
      study population. To this end, a DNA-pooling technique was used to screen
      microsatellite and diallelic insertion/deletion markers for allele-frequency
      differences between putative representatives of the parental populations of the
      admixed Mexican American (MA) and African American (AA) populations. Markers with
      promising pooled differences were then confirmed by individual genotyping in both
      the parental and admixed populations. For the MA population, screening of >600
      markers identified 151 ethnic-difference markers (EDMs) with delta>0.30 (where
      delta is the absolute value of each allele-frequency difference between two
      populations, summed over all marker alleles and divided by two) that are likely
      to be useful for MALD analysis. For the AA population, analysis of >400 markers
      identified 97 EDMs. In addition, individual genotyping of these markers in Pima
      Amerindians, Yavapai Amerindians, European American (EA) individuals, Africans
      from Zimbabwe, MA individuals, and AA individuals, as well as comparison to the
      CEPH genotyping set, suggests that the differences between subpopulations of an
      ethnicity are small for many markers with large interethnic differences.
      Estimates of admixture that are based on individual genotyping of these markers
      are consistent with a 60% EA:40% Amerindian contribution to MA populations and
      with a 20% EA:80% African contribution to AA populations. Taken together, these
      data suggest that EDMs with large interpopulation and small intrapopulation
      differences can be readily identified for MALD studies in both AA and MA
      populations.

PMID- 11845414
TI  - Orthostatic blood pressure testing.

PMID- 11845415
TI  - Is meta-analysis clinically useful for perianesthesia nurses.

PMID- 11845417
TI  - Perianesthesia care of cardiac surgery patients: a CPAN review.

PMID- 11845418
TI  - Historical opportunity to participate in changing practice.

PMID- 11845419
TI  - A position statement on pain management. American Society of Perianesthesia
      Nurses.

PMID- 11845420
TI  - PACU pain management algorithm.
AB  - Effective and safe pain management for a patient emerging from the effects of
      anesthesia is a specialized skill that is often acquired only through years of
      experience. This article provides perianesthesia nurses with a technique to
      assess the cognitively impaired postanesthesia patient and to incorporate vital
      circumstantial criteria in determining the presence of pain. Intervention
      recommendations are also included. The pain management algorithm includes
      research-based information from the following sources: Pain: Clinical Manual (ed
      2), by pain nurse experts Margo McCaffery, RN, MS, FAAN, and Chris Pasero, RN,
      MS; and the American Pain Society's Principles of Analgesic Use in the Treatment
      of Acute Pain and Cancer Pain (ed 4). Parameters are incorporated for clinical
      use.

PMID- 11845421
TI  - Evaluation of an acute pain service.
AB  - Implementation of an acute pain nurse role and the expansion of the Acute Pain
      Service (APS) at a newly merged Canadian hospital system led to an evaluation of
      these programs. A literature review of APSs showed that the services with an APS
      nurse had improved patient outcomes. As a result, a PACU nurse was added to the
      APS at all hospitals, and all services were restructured. Surveys conducted one
      year after this reorganization showed very positive response ratings in the areas
      of quality of care, but mixed results in other areas including education and job
      satisfaction. Flow diagrams for the clinical units were developed, and both
      structured and informal education sessions were provided. The description of the
      APS nurse's role was also redefined.

PMID- 11845422
TI  - Postoperative pain management: morphine versus ketorolac.
AB  - Without proper management, postoperative pain can grow to intolerable levels and
      interfere with functioning and healing. Historically, morphine had no equal for
      postoperative pain management. Its side effects, however, are troubling.
      Recently, researchers have developed many analgesics that do not induce the same
      side effects as morphine. Ketorolac is one example. Nevertheless, a single drug
      with an efficacy comparable with morphine remains elusive. In this article, the
      physiology of pain is reviewed and ketorolac is compared with morphine.
      Perianesthesia nurses are given pertinent information to enhance their ability to
      provide the best pain relief available for the patients in their care.

PMID- 11845423
TI  - General surgery overflow: a new challenge for the PACU.

PMID- 11845424
TI  - Patient preparation: the physical assessment.

PMID- 11845425
TI  - Herbal supplements: healthy or harmful?

PMID- 11845426
TI  - Ethical considerations in nursing research.

PMID- 11845427
TI  - Diabetic emergencies.

PMID- 11845428
TI  - Snow day.

PMID- 11845429
TI  - Analysis by flow cytometry of the subpopulations of lymphocytes from the
      peripheral blood of procain or diethylaminoethanol treated rabbits.
AB  - The authors worked on 3 groups of 8 male rabbits, New Zealand race: 1) controls;
      2) procain injected i.m., 15 mg/kg body weight, daily, for 30 days; 3) i.m.
      injected with diethylaminoethanol (DEAE), 15 mg/kg body weight, daily, for 35
      days. The expression of the MHC I, MHC II, CD43, CD4 and IgM antigenic markers on
      the plasmatic membrane of the lymphocytes was studied using flow cytometry and
      monoclonal antibodies. Procain or DEAE treatment reduced the percentage of
      lymphocytes expressing I MHC, from 99.06 in the control group, to 94.51 in
      procain group and to 96.91 in the DEAE group. The intensity of expression of MHC
      complexes of class II decreases from 160.94 in the control group, to 107.21 in
      the procain group and to 104.05 in the DEAE group. No significant differences
      were noticed between the three groups of rabbits concerning the rate of
      lymphocytes that have on their surface expressed markers for CD43 (lymphocytes
      T), CD4 (Th), or IgM (lymphocytes B). Lymphocytosis induced in rabbits as a
      result of the DEAE treatment took place without a change in the proportions of
      lymphocyte subpopulations. The authors consider that owing to their capacity to
      reduce the expression of antigens MHC of class I and class II on the membrane of
      lymphocytes, procain and DEAE can have benefic effects in some autoimmune,
      autoaggression and inflammatory diseases.

PMID- 11845430
TI  - Frequency and distribution per species, biotypes, resistance to antibiotics and
      beta-lactamase production of the haemophils isolated from patients with
      respiratory diseases.
AB  - A number of 150 samples were prelevated from respiratory tract secretions of 88
      patients with respiratory infections and three healthy subjects; 162 haemophilus
      strains were isolated, identified and studied and the following results were
      obtained: H. parainfluenzae was isolated from tonsillitis and laryngitis--over
      70%, bronchitis--58% and pharyngitis--56.6%; H. influenzae was isolated from
      pharyngitis--26.4%, bronchitis--16.1% and tonsillitis--13.6% cases; H.
      parahaemolyticus from bronchitis--19.3%, tonsillitis--13.6% and laryngitis. H.
      paraphrophilus was isolated (6.8%) from pharyngitis, tonsillitis, sinusitis,
      bronchitis and pulmonary abscess and H. paraphrohaemolyticus was isolated--4.5%
      from pharyngitis, synusitis, bronchitis and pulmonary sarcoidosis. Most of the
      isolates belonged to biotype II H. influenzae and biotypes II, I, III H.
      parainfluenzae. Haemophils were 100% sensitive to Ofloxacin and resistant to Cro-
      13.5%, Do--17.9%, C and Caz--22.2%, Aml--24.6%, Rd--40.7%, Amp--41.9% and Te-
      63.5%; varying according to the haemophilus species. H. influenzae was resistant
      to Do--14.2%, Caz and C--21.4%, H. parainfluenzae was resistant to Cro--11%, Do-
      22%, whilst H. parahaemolyticus was resistant to Do--9% and to Aml, Caz and Cro-
      13.6%. Haemophils isolated from sputum showed a resistance higher by 12-34% and 6
      17% than those isolated from other specimens, such as pharyngeal exudate, where
      the resistance to rifadin was lower by 10%. beta-lactamases were present in 27.7%
      of the strains: H. parainfluenzae--36%, H. paraphrohaemolyticus--25%, H.
      influenzae--17.8% and H. parahaemolyticus--15.7%; in strains from sputum--34.2%,
      pharyngeal exudate--28.8% and from other specimens--6.6%. No correlations were
      noticed between the biotype and the clinical manifestation or the resistance to
      the antibiotic, a higher frequency of beta-lactamase production being reported in
      H. influenzae biotype V and H. parainfluenzae biotypes II and IV.

PMID- 11845431
TI  - Phenotypic characterization of some anginosus group isolates from oral and
      maxillofacial infections.
AB  - The aim of this study was to briefly characterize serologically, biochemically
      and from the cultural point of view some anginosus group isolates found in pus
      samples collected from patients with oral and maxillofacial infections. Cultural
      characterization was done by studying the culture odor, the colony size and
      aspect, and hemolysis type on Columbia bood agar (BA). Lancefield grouping was
      made on cards using the rapid latex-agglutination test (Slidex Strepto-Kit, Bio
      Merieux, France). The biochemical characterization was performed at the same time
      with the speciation by the Rapid ID 32 Strep system (Bio Merieux, Marcy-l'Etoile,
      France). The anginosus group isolates were phenotypically heterogenic. Based on
      phenotypic description, nonidentical anginosus group isolates were found in the
      same patient sample.

PMID- 11845432
TI  - Effect of viral preinfection upon cell adherence in some staphylococcus strains
      from specific infections or carriers.
AB  - The adherence of bacteria to eukaryote cells has been largely investigated as an
      essential step in the occurrence of bacterial infection. Some clinical and
      epidemiological studies have revealed the frequent association of certain viral
      infections with bacterial infections originating in the same ecological niche.
      Therefore, we investigated the effect of the viral preinfection (ADV4) of some
      cultivated cells (HEp-2 and IC.SK-27) upon the adherence of staphylococcus to
      these cells. The analysis of cell adherence within the mentioned conditions,
      estimated by flow cytometry, allowed of the following conclusions: 1. bacterial
      adherence to cultivated and virally preinfected cells is augmented by the viral
      preinfection, and its value on a given cell substrate may characterize a
      bacterial strain; 2. bacterial adherence to the investigated cell substrates does
      not correlate with the origin of the tested staphylococcus strains (infections or
      carriers) and some cell lines can differentiate bacterial strains depending upon
      the ecological niche or inside it.

PMID- 11845433
TI  - Multi-way flow cytometric immune monitoring of antiretroviral therapy in HIV
      infected children.
AB  - In 40 HIV-infected children, 8-10 years old, belonging to the category A state of
      infection, the following flow-cytometric parameters were scored: percentage
      levels of different blood lymphocytes; surface expression of some activation and
      memory markers in CD4+ cells; switch to Th1 or Th2 of in vitro -stimulated CD4+
      cell, tested by intracellular production of interleukin-2 or interleukin-4. Each
      investigation was carried out both before and 3 months after antiretroviral
      therapy (AZT and ddC). Some post-therapy changes concerning blood lymphocyte
      percentages were noticed, not only within CD4+ subpopulation, but also within
      CD8+, HLA-DR+/CD3 (T-activated) and CD16+CD56+ cells, respectively. On the other
      hand, following antiretroviral treatment, in HIV- originated CD4+ fresh cells, an
      improvement of pre-therapy increased values of surface activation (CD69, CD25)
      markers on memory (CD45RO+) cells, as well as of pre-therapy reduced rate of
      switching to Th1, revealed by intracellular interleukin-2 synthesis, was found.
      The significance of data obtained in the multi-way immune monitoring of
      antiretroviral therapy, in pediatric AIDS, as an additional investigation panel,
      is discussed.

PMID- 11845434
TI  - Photodynamic therapy: an update.
AB  - Photodynamic therapy (PDT) is a promising local treatment modality based on the
      selective accumulation of a photosensitizer in malignant tissues and the
      subsequent irradiation with laser light. Photodynamic therapy of malignant tumors
      includes biological, photochemical and photophysical processes. These processes
      involve: (a) absorption of photosensitizing agent; (b) selective retention of the
      photosensitizer in tumors and (c) irradiation of sensitized tumor by laser
      radiation. This report provides a review of photosensitizers, photochemistry,
      subcellular targets, side effects and laser involved in photodynamic therapy. In
      addition, gradual increase in knowledge related to in vitro and in vivo
      mechanisms of action of PDT, as well as some clinical applications of
      photodynamic therapy are presented.

PMID- 11845435
TI  - A purified green barley extract with modulatory properties upon TNF alpha and ROS
      released by human specialised cells isolated from RA patients.
AB  - Based on the finding that reactive oxygen species (ROS) play important roles in
      mediating proinflammatory cytokine production (e.g. TNF alpha) and that many
      plant extracts contain substances with antioxidant properties, we examined the
      antiinflammatory action of a green barley extract, commercially available as
      "Natural SOD". The results obtained in this study demonstrate that the
      antiinflammatory properties of "Natural SOD" due to its micromolecular
      substances, able to scavenge ROS and to down-regulate TNF alpha production, main
      inflammation mediators produced by specialised cells from peripheral blood (PB)
      and synovial fluid (SF) of patients with rheumatoid arthritis (RA). We prepared
      and tested a purified green barley extract (PE) containing micromolecular
      substances under 1 kDa, able to inhibit TNF alpha releasing--measured by an
      bioassay--from LPS stimulated human mononuclear cells (MNC) isolated both from PB
      and SF of RA patients. Luminol-dependent chemiluminescence has been used to
      measure the scavenging activity of PE on ROS releasing from activated neutrophils
      isolated from PB of RA patients. PE, containing high concentrations of substances
      with antioxidant and antiinflammatory properties, could be a more efficient
      natural drug for human use than "Natural SOD" in the treatment of RA patients.

PMID- 11845436
TI  - The influence of synovial fluid on lymphocyte functions in rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a chronic recurrent and systemic inflammatory
      disease affecting around 1% of the population, that primarily involves the
      joints. In this study, we determined the Th1/Th2 lymphocytes ratio at the site of
      rheumatoid inflammation and the influence of the synovial fluid (SF) on the
      secretory and proliferative function in synovial fluid mononuclear cells (SFMC)
      and peripheral blood mononuclear cells (PBMC), obtained from patients with RA.
      Our results showed significant differences concerning the mononuclear cells and
      the CD4/CD8 ratio in synovial fluid and peripheral blood of patients. In SF
      prevailed Th1 cells, while in peripheral blood we found another cytokine profile
      of T lymphocytes. Also synovial fluid lymphocytes had a low PHA-stimulated
      blastogenic response. Patients plasma and synovial fluid showed an inhibitory
      effect on prolipheration indexes.

PMID- 11845437
TI  - Negatively charged liposomes as immunological adjuvant for tetanus and diphtheria
      toxoids.
AB  - The aim of this study is to develop the previous research on tetanus toxoid and
      improve the level of antibodies against tetanus and diphtheria toxoids using
      liposomes as adjuvant. The results show that negatively charged liposomes enhance
      the immune effects of the combination of the two vaccines.

PMID- 11845438
TI  - Liposomes as immunological adjuvants for tetanus vaccine.
AB  - Finding a new immunological adjuvant has been a challenge all along. The aim of
      our study is to improve the level of antibodies against tetanus using liposomes
      as adjuvant. As can be seen from the results of our study, the liposomes are a
      competitive candidate in this respect.

PMID- 11845439
TI  - ELISA assays for the detection of Bothrops lanceolatus venom in envenomed patient
      plasmas.
AB  - A double antibody sandwich enzyme linked immunosorbant assay (ELISA) was carried
      out to detect Bothrops Ianceolatus venom in plasma from envenomed patients at
      various time intervals (0, 6, 12, 18 and 24 hrs). The test could detect Bothrops
      lanceolatus levels up to 12 ng/mL of envenomed patient plasmas. Elaboration of an
      easy, fast and species-diagnostic based on this ELISA technique useful to
      physicians is discussed.

PMID- 11845440
TI  - Synthesis and molecular mechanical studies of antiviral copper(II) complexes with
      morpholinebiguanide drug.
AB  - The synthesis and characterization of new Cu(II) complexes with
      morpholinebiguanide drug are described. The complexes formed have been
      characterized by elemental analysis, IR, UV-VIS, conductance measurements, EPR
      spectra and magnetic susceptibility measurements. Their biological activity is
      supported by the experimental data and enhanced by the theoretical ones. The
      morpholinebiguanide ligand and their copper(II)-complexes were studied by
      molecular mechanics program.

PMID- 11845442
TI  - Th1 cytokines in autoimmune thyroiditis.
AB  - This study was performed on a lot of 51 patients and intends to correlate the
      autoimmune thyroiditis to the synthesis of Th1 cytokines and to the activation of
      T lymphocytes. We find out that CD25, an activation marker of T lymphocytes, is
      significantly increased in these patients. We also find out that certain cytokine
      serum levels are increased (IL-2, TNF-alpha, IFN-gamma). These cytokines
      correspond to the secretor profile of the Th1 subset. Mononuclear cell culture
      supernatants showed an increased level of IL-2 and TNF-alpha in samples
      stimulated with ConA in comparison to unstimulated samples from the same patient,
      suggesting the existence of an expansioned Th1 and CD8+ cytotoxic population.

PMID- 11845441
TI  - Proinflammatory cytokines production and PMN-elastase release from activated PMN
      cells in the periodontal disease.
AB  - The aim of this study was to evaluate the local changes in the crevicular
      gingival fluid (CGF) determined by the inflammatory and immune response in
      periodontitis and gingivitis. The selected patients presented gingivitis (n = 9)
      and periodontitis: aggressive periodontitis (n = 21) and adult periodontitis (n =
      8). The crevicular fluid was provided from the gingival and periodontal pocket.
      The measurement of PMN-elastase in the CGF, using the ELISA method, showed a
      significant (p < 0.01) increase of the enzyme concentration in the aggressive
      periodontitis group (62.1 +/- 3.91 ng/ml) comparing to the gingivitis group
      (33.04 +/- 4.14 ng/ml) but also the increase (p < 0.05) of this enzyme in the
      adult periodontitis (43.6 +/- 2.16 ng/ml) comparing to the gingivitis, which
      indicated the evolutive aspects of the inflammatory reaction in these diseases.
      The increased production of PMN-E is the result of the activation of
      polymorphonuclear cells (PMN) as a reaction of the microbial attack.
      Degranulation and release of proteolytic enzymes including elastase, which
      present cytotoxic capacities, follow the activation of neutrophil granulocytes
      (PMN). The activated granulocytes release proinflammatory cytokines IL-1, TNF
      alpha which augment the inflammatory immune response. The aggressive
      periodontitis group showed an increased CGF level of IL-1 (780.4 +/- 104 pg/ml)
      comparing to the gingivitis group (275.5 +/- 78 pg/ml) (p < 0.01). TNF-alpha also
      presented an increased level (p < 0.01) in the aggressive periodontitis group
      (16.3 +/- 2.3 pg/ml) comparing to the gingivitis group (4.1 +/- 1.2 pg/ml) as a
      consequence of the periodontium destruction and of the tissular necrosis in the
      former group. In conclusion, our study shows a significant increase of the PMN
      elastase and proinflammatory cytokines level in CGF of patients with gingivitis
      and periodontitis. The intensity of the inflammatory response in these diseases
      is strongly correlated to the activation of the neutrophil granulocytes which
      release these biological active molecules that could be used as evolution markers
      of the disease.

PMID- 11845444
TI  - Streptococci species of anginosus group isolated from oral and maxillofacial
      infections.
AB  - The aim of the study was to isolate and identify at species level streptococci
      strains of anginosus group in pus samples collected from 110 patients with oral
      and maxillofacial (OMF) infections. Gram-stained smears and cultures on selective
      and nonselective media were done from each of the 111 pus samples (2 samples were
      collected from one of the patients, who presented 2 oral abscesses at the same
      time). The isolates were identified on the basis of cultural and biochemical
      characteristics. Speciation of the anginosus group isolates was performed using
      the Rapid ID 32 Strep system (Bio Merieux, France). Fourty-four anginosus group
      strains were isolated from 42 patients. Fourty of these isolates were identified
      as Streptococcus anginosus (2 nonidentical isolates were found in 2 patients), 3
      isolates as Streptococcus constellatus and only one as Streptococcus intermedius.
      The study confirmed that the anginosus group is often involved in OMF infections
      alone or in association with other aerobic and/or anaerobic bacteria. In the
      investigated cases, Streptococcus anginosus was by far the most frequently
      isolated species within the anginosus group.

PMID- 11845443
TI  - A particular structure associated to the nucleoid of cyanobacteria.
AB  - Regressive staining as well as beta-radiations or trypsin treatment on
      Synechocystis PCC6803 and Spirulina platensis (Gom,-Geilteri.) whole cells or
      permeaplasts, respectively, have demonstrated the presence of a particular
      structure associated to the nucleoid of cyanobacteria. This structure with a
      tridimensional network aspect has been called scaffold-like. We presume that it
      represents the cellular-molecular support for the supercoiling of the nucleoid of
      cyanobacteria.

PMID- 11845445
TI  - Nature, nomenclature and taxonomy of obligate methanol utilizing strains.
AB  - In a screening program, a number of different bacterial strains with the ability
      to utilize methanol as a sole carbon and energy source were isolated and
      described. They are well known methanol utilizing genera Pseudomonas, Klebsiella,
      Micrococcus, Methylomonas or, on the contrary, the new, unknown genera and
      species of methylotrophic bacteria. In the last category, Acinetobacter and
      Alcaligenes are the new reported genera of organisms able to use methanol as a
      sole carbon and energy source. The present paper reports the very complex
      physiological and biochemical modifications when very versatile bacteria such as
      Pseudomonas aeruginosa and Acinetobacter calcoaceticus are cultured on methanol
      and when the obligate methylotrophic state is compared with the facultative
      methylotrophic state of the same bacterial strain. Based on experiments and
      comparisons with literature data, it seems that Methylomonas methanica is the
      obligate methylotrophic state of Pseudomonas aeruginosa and that Acinetobacter
      calcoaceticus is the facultative methylotrophic state of Methylococcus
      capsulatus, an obligate methylotroph. The relationship of the obligate to the
      facultative and of the facultative to the obligate methylotrophy were
      established. These new methylotrophic genera and species, the profound
      physiological and biochemical modifications as well as the new data concerning
      nature, nomenclature and taxonomy of methanol utilizing bateria were reported for
      the first time in 1983.

PMID- 11845446
TI  - Antimicrobial susceptibility of some streptococci strains of anginosus group
      isolated from oral and maxillofacial infections.
AB  - Streptococci strains of the anginosus group isolated from various oral and
      maxillofacial infections (OMF) were screened for their susceptibility to the
      following antimicrobial agents: benzylpenicillin, ampicillin, oxacillin,
      cephalothin, ceftazidime, cefotaxime, cefuroxime, erythromycin, clindamycin,
      tetracycline, chloramphenicol, vancomycin and trimethoprime-sulphamethoxazole.
      The isolates were susceptable to: clindamycin, chloramphenicol, vancomycin and
      all beta-lactam antibiotics, except ceftazidime to which 54.5% of the strains
      showed intermediate susceptibility. Intermediate susceptibility to tetracycline
      was found in 11.3% of the strains, whereas resistance to the same antibiotic was
      demonstrated in 61.4%. Resistance to erythromycin and trimethoprime
      sulphamethoxazole was of 2.3% for both. In conclusion, penicillin is the drug of
      choice in infections caused by streptococci of the anginosus group.

PMID- 11845448
TI  - Hepatic hematopoiesis in adult mouse during experimental rodent malaria.
AB  - During rodent malaria the development of the hematopoiesis in the liver was
      observed. This fact was used as a model for the study of the conditions and the
      features of the extramedullary hematopoietic differentiation, following the state
      of anaemia induced by parasitemia with Plasmodium berghei. Histological and
      ultrastructural data on the hepatic hematopoiesis are presented.

PMID- 11845447
TI  - Ultrastructural modifications at uterine cervix level induced by human
      papillomaviruses infections.
AB  - The paper presents the ultrastructural modifications occurring in uterine cervix
      epithelium in 10 patients with clinical susceptibility of HPV infections. The
      presence of viral HPV particles was identified in 5 cases and in 1 case the
      concomitant presence of both HPV and HSV2 particles was detected. The maximum
      amount of HPV virions is found in the spinous and superficial layer, particularly
      in the nucleus, but also in cytoplasm. In all the studied cases, cellular
      alterations were present in the whole depth of the epithelium. The degree of
      cellular alterations depends upon the epithelial layer to which they belong and
      to the stage of the disease as well. Cellular alterations are more pronounced at
      the level of the spinous and superficial layer being present both in nucleus
      (chromatin condensations, invaginations of the nuclear membrane, the occurrence
      of some pseudonuclei) and cytoplasm (intracytoplasmic vacuolizations, the
      presence of some inclusions). The presence of some giant mono- and binucleated
      cells as well as the formation of cellular syncytia in case of severe alterations
      are also reported.

PMID- 11845449
TI  - Experimental studies on the bacterial product CANTASTIM derived from Pseudomonas
      aeruginosa. V. Protective effect in endotoxin shock.
AB  - In this paper, we investigated the effect of the treatment with the bacterial
      immunomodulator CANTASTIM in a model of endotoxin shock in mice. Among the
      different mouse models described for septic shock, we have chosen the low-dose
      endotoxin model using D-galactosamine sensitized mice. We noticed a significant
      increase in the survival rate of the mice treated with CANTASTIM before the
      endotoxin challenge. This protective effect was correlated with a strong
      reduction in the level of TNF alpha in the sera of treated mice. Prior exposure
      to CANTASTIM also attenuated subsequent ex vivo nitric oxide production by
      peritoneal macrophages of the mice. In this model of endotoxin shock, the major
      role has been attributed to TNF alpha acting through its receptor TNFRI (p55). A
      downregulation of this receptor as a consequence of the treatment with CANTASTIM
      may be hypothesized. However, the intervention of CANTASTIM in other points in
      the cytokine network involved in endotoxin shock cannot be excluded.

PMID- 11845450
TI  - Serodiagnosis of extrapulmonary tuberculosis by enzyme-linked immunosorbent assay
      (ELISA).
AB  - Antibodies against Mycobacterium tuberculosis antigenic glycolipids were
      determined by enzyme-linked immunosorbent assay (ELISA). The 720 sera were
      collected from adult patients under investigation, suspected with extrapulmonary
      tuberculosis. The test performance was estimated according to definitive
      diagnosis in terms of specificity, sensitivity, positive predictive value and
      negative predictive value. These parameters calculated on 142 sera from patients
      with extrapulmonary tuberculosis and on 578 sera from patients with different
      nontuberculosis diseases were 92%, 81.6%, 70.9% and 95.1%, respectively. The
      specificity decreased to 85% when tuberculosis was associated with cancer or
      hepatic cirrhosis. In reactivated tuberculosis the sensitivity and the positive
      predictive value were 86.9% and 83.3%, respectively. Our results showed that
      ELISA was conclusive for patients with active tuberculosis, before the initiation
      of the treatment. The sensitivity decreased to 30% in inactive forms. It was
      demonstrated that ELISA was positive in cases with negative microscopy
      genitourinary tuberculosis. ELISA could be used as a supporting test in the
      laboratory diagnosis of active extrapulmonary tuberculosis in adults,
      disregarding the site involved.

PMID- 11845451
TI  - ICAM-1, ELAM-1, TNF-alpha and IL-6 in serum and blister liquid of pemphigus
      vulgaris patients.
AB  - The levels of ICAM-1, ELAM-1, TNF-alpha and IL-6 were determined in 12 patients
      with pemphigus vulgaris (PV) both in serum and the blister liquid. As a control,
      the same parameters were determined in 7 patients with herpes zoster (HZ). The
      patients with PV presented significantly higher values of ICAM-1 in the blister
      liquid, as compared to the serum values. The values of TNF-alpha and IL-6 were
      increased both in serum and the blister liquid. The ELAM-1 values did not show
      significant differences between serum and the blister liquid. In HZ patients, the
      blister liquid values did not significantly exceed the serum values both for ICAM
      1 and ELAM-1. TNF-alpha and IL-6 presented high values both in serum and the
      blister liquid. We consider that the high values of ICAM-1 in the blister liquid
      from PV patients suggest the involvement of this adhesion molecule in the PV
      pathogenic features. The implication of ICAM-1 could be nonspecific and limited,
      and could possibly represent a reaction to the destruction of the desmosomal
      bonds within keratinocytes.

PMID- 11845452
TI  - Use of the presence of anti-protein gag antibodies as an evolution marker of HIV
      infection.
AB  - The paper studies the modifications occurring in the prevalence of anti-protein
      gag antibodies during the evolution of the infection in a paediatric population
      iatrogenically infected and not submitted to antiretroviral treatment. The study
      was performed by annual clinical examination of children and by laboratory
      determinations: western-blot, p24 Ag assay, determination of lymphocyte
      population by flowcytometry. The predictive capacity of p17 antibodies was
      revealed, their occurrence after seroconversion pointing to a favourable
      evolution, with a longer asymptomatic period; the disappearance of these
      antibodies during the disease indicates a more advanced stage of the disease. The
      disappearance of p24 and p55 antibodies during the evolution of the disease shows
      a more advanced stage of the disease, both clinically and as concerning the
      immunosuppression degree.

PMID- 11845453
TI  - Cell culture procedure and the optometric method to study cells in vitro.
AB  - The cells are cultivated using an original licensed procedure named "homogeneous
      sets". This consists of cell growth in monolayer using as holder several plates
      specially designed to enable the study both by use of the optometric method we
      elaborated and by classical techniques (microscopy). Using the suggested method,
      a stress can be induced under control. Stress induction is undertaken through
      physical, chemical, biological factors or all of these taken together. The
      reactivity to stress consists of changes in cell morphology, which can be
      evidenced by graphically recording the optical density variation in time,
      contraction curves being thus obtained. Dimensions, the initial and final values,
      the characteristic zones, angles and the arrow are thus chosen as to characterize
      the cell reactivity and the most significant periods of time during the
      experiment. The contraction curves can be interpreted somewhat similarly to the
      electrocardiogram, so that the term we chose is the "OPTOGRAM". The recovery to
      the cells normal state is ascertained by the relaxation curves. The cell culture
      procedure and the optometric evaluation method provide the means to study cell
      reactivity to different aggressive or protective agents.

PMID- 11845454
TI  - Studies on pathogenicity of Yersinia enterocolitica in mice with diabetes
      mellitus.
AB  - In this study, we investigated the colonizing ability as well as the association
      of Yersinia enterocolitica serotype 0:9 to epithelial cells of the intestinal
      tract, Peyer's patches, mesenteric lymph nodes, liver, spleen and lungs in
      Alloxan-induced diabetes mellitus in mice and controls. The results showed that:
      (a) in diabetic mice the Y. enterocolitica colonizing values were in range of
      10(6.5)-10(8.25) CFU/g of feces; (b) maximum colonizing values were found in
      distal ileum and Peyer's patches and lower in colon; (c) the infection was
      progressive with dissemination of bacteria in the liver, spleen and lung; (d) in
      control (non-diabetic) mice, the colonizing values were 10-100 times lower than
      those found in the diabetic batch; (e) the main histopathological changes
      noticed, namely ileitis, mesenteric lymphadenitis and septicemia, were presumably
      induced by high bacterial load in the liver, spleen and lung leading to a septic
      course of infection as well as toxic effects of heat-stable enterotoxins of Y.
      enterocolitica (Yst). The results were confirmed by electron microscopy
      observations. Summing up, these results demonstrate that diabetic mice were more
      susceptible to Y. enterocolitica cells than normal mice.

PMID- 11845455
TI  - The antimicrobial susceptibility of Escherichia coli isolated in eastern area of
      Romania. A surveillance study.
AB  - To evaluate the resistance trends for Escherichia coli isolates during 1993-1999
      period in Eastern Romania to: ampicillin (A), ampicillin-sulbactam (A/S),
      ceftazidime (CAZ), cefotaxime (CTA), ceftriaxone (CRO), aztreonam (AZT),
      ofloxacin (OF), ciprofloxacin (CIP), tetracycline (T) and chloramphenicol (C). We
      tested 2012 clinical isolates obtained from faeces and urine. MICs were
      determined by a dilution method in Mueller-Hinton agar (NCCLS guidelines).
      Resistance rates were analyzed using the NCCLS breakpoints for the fully
      susceptible category (moderately susceptible strains were classified as
      resistant). No significant differences were observed in susceptibility of E. coli
      to ampicillin and ampicillin/sulbactam in the last years. The high percentage of
      resistant isolates was observed in 1995 for ampicillin (89.7%). Higher incidences
      of resistance were detected for A, A/S, T; the addition of sulbactam restored A
      susceptibility only for a small percent. CAZ, CTA, CRO, AZT, OF and CIP
      resistance among E. coli isolates was progressively increased in the last period.

PMID- 11845456
TI  - Recommendations for fungal opportunistic infections prevention in persons
      infected with human immunodeficiency virus.
AB  - Fungal infections have become important causes of morbidity and mortality in
      immunocompromised hosts, including those with the acquired immune deficiency
      syndrome (AIDS). Although significant therapeutic advances are being made in the
      field of antiretroviral therapy, parallel advances must be attained in the
      management of secondary infections, including those due to fungi. As increasing
      numbers of people with HIV infection come in to medical attention, the problem of
      fungal infections will also increase, requiring innovative approaches toward
      understanding the pathogenesis of these infections and developing new diagnostic
      and therapeutic modalities. A better understanding is required for the
      immunopathogenesis of fungal infections. Improved understanding of new and
      established antifungal agents in conjunction with ART agents as well as immune
      modulators, should yield important advances in prevention, control and treatment
      of fungal infections of HIV infected people.

PMID- 11845457
TI  - Parentage analysis for three Romanian families by DNA-fingerprinting.
AB  - In forensic medicine, DNA fingerprinting for human identification and paternity
      testing is becoming a necessary procedure. The genetic locus D1S80 (MCT118) with
      Hinf I polymorphism of its 5' flanking sequence, HUMTH01 and D21S11 have been
      successfully amplified from human genomic DNA isolated from blood (50 ng from
      each sample) by the polymerase chain reaction (PCR) using oligonucleotide primers
      complementary to the flanking sequences as primers for amplification. DNA bands
      were detected by ethidium bromide staining after electrophoresis on agarose gels
      or high-resolution SDS-PAGE. Analysis of these VNTR loci was thus achieved
      without the need for Southern blot or radioactive material. The small size of the
      DNA fragments produced in the PCR amplification permitted good resolution of
      individual alleles. The precise specification of the number of tandem repeats
      present in each allelic fragment was reproducible from one analysis to another.
      The aim of this study includes three paternity testing cases; they are the first
      three human DNA-fingerprints performed in Romania.

PMID- 11845458
TI  - Four cases of human filariosis due to Setaria labiatopapillosa found in
      Bucharest, Romania.
AB  - We record the occurrence of four cases of subconjunctival eye infection due to
      Setaria labiatopapillosa. The patients are all women, between 35 and 68 years
      old, all inhabitants of the same neighbourhood of the lake Pantelimon, a well
      known area for its blood feeding vector insect population and all complained
      about the same eye affliction: photophobia, eye swelling, tearing and foreign
      body sensation accompanied by some rash and low eosinofilia (6-8%). The treatment
      was surgical (excision) and DEC 1 mg/kg body weight. The vector insect cannot be
      specified. We stress that to our knowledge these are the first reported cases of
      human infection with Setaria labiatopapillosa.

PMID- 11845459
TI  - Complex compounds of Pd(II), Pt(II), Cu(I) and Hg(II) with tertiary thioamides.
AB  - Synthesis and chemical and physical characterization of four new complex
      compounds of thiobenzpyrolidide [1-(pyrolidine)-thiobenzoyl] with Pd(II), Pt(II),
      Cu(I) and Hg(II) are presented. The purposed chemical structure for these
      complexes is suggested by the elemental chemical analysis, molecular mass
      measurements, electric conductivities as well as by UV-VIS and IR spectra. The
      obtained compounds may in principle be used as enzyme inhibitors having a
      pronounced insecticidal action.

PMID- 11845460
TI  - Immune response to Escherichia coli antigens entrapped in liposomes. I.
      Immunopathological studies.
AB  - In this study, we have searched for an effective mucosal delivery system for a
      purified E. coli antigen which elicits anticolonization and anti-toxic immunity.
      E. coli colonization factor antigen (CFA/I) and heat-labile enterotoxin (LT) were
      encapsulated in liposomes. To determine the efficacies of soluble and liposome
      encapsulated E. coli antigens young rabbits were mucosally treated with three
      oral doses of E. coli antigens given 7 days apart. Ten days after the last
      booster, rabbits were orally challenged with 5 x 10(9) bacterial cells (O78:H11
      serotype). The experimental results allow of making some remarks which can be
      correlated with the protection obtained in vaccinated animals: (a) immunization
      with E. coli antigens entrapped in liposomes ensured protection against ETEC
      strains; (b) lower protection against homologous and heterologous CFA/I +(LT-
      ST+) strains were noticed; (c) adhesion of labelled -3H-leucine-bacteria to the
      intestinal mucosa revealed a maximum distribution in duodenum-jejunum and minimum
      in the colonic mucosa; (d) it contributed to the release of inoculated virulent
      bacteria from intestinal tract; (e) humoral, cellular and histopathological
      findings confirm the afore mentioned observation. Summing up, these results
      suggest that liposomes are very good carriers for E. coli antigens and these
      findings highlight the potential use of LT and CFA/I antigens entrapped in
      liposomes as mucosal and humoral induction of immune response and make them a
      candidate for future use in prophylaxis of diarrhoea in man.

PMID- 11845461
TI  - The levels of neutrophils oxidative burst in rheumatic disorders.
AB  - We investigated the participation of the polymorphonuclear leukocytes (PMNs) as
      mediators of tissue destruction in 2 variants of rheumatic disorders that affect
      primarily the joints: the rheumatoid arthritis (RA) and the osteoarthritis (OA).
      We noted significant differences in the number of PMNs present at the joint
      level, which was low in OA and high in RA. The unstimulated and in vitro
      stimulated with opsonized zymozan (OZ) or ConA PMNs from the peripheral blood of
      these two groups of patients released a normal level of oxygen free radicals
      (OFR). On the contrary, the neutrophils isolated from the synovial fluid (SF) of
      RA patients showed a distinct feature: the unstimulated cells released high
      amounts of OFR, while those in vitro stimulated with OZ or ConA presented a low
      level of respiratory burst. In OA both in vitro unstimulated and stimulated with
      OZ or ConA neutrophils isolated from the SF had diminished values of OFR
      released. We assume that the chemiluminescence assay could detect distinct
      differences of the PMNs implications in RA and OA injuries and may be a
      laboratory test in the differential diagnosis of these rheumatic disorders.

PMID- 11845462
TI  - Shift toward T lymphocytes with Th1 and Tc1 cytokine-secterion profile in the
      joints of patients with osteoarthritis.
AB  - Osteoarthritis (OA), although a heterogeneous disease, is generally believed by
      rheumatologists to be primarily a disease generated by biomechanical alterations.
      In order to determine the role of T cells, the pattern of T lymphocyte cytokines
      and to characterize the mononuclear cells from both peripheral blood (PB) and
      synovial fluid (SF) from patients with OA flow cytometry with a panel of
      monoclonal antibodies recognising CD4, CD8 and intracellular cytokines (IL2, IL4,
      IL10, gamma-IFN) was employed. The coexpression of CD4 and CD8 markers only on
      the SF T cells surface after in vitro stimulation by phorbol-miristate acetate
      and ionomicine, but not on PBL or in vitro unstimulated SFL was noted. The
      intracellular IFN-gamma was detected in enhanced levels in both CD4+ and CD8+ SF
      T cells, while the IL2 contents was not different in PB and SF samples. The
      Th2/Tc2 cytokines (IL4 and IL10) were detected in low amounts in both PBL and
      SFL. This study shows the role of some T cell populations and cytokines in the
      generation of joint destruction in osteoarthritis.

PMID- 11845463
TI  - Familial lupus anticoagulant.
AB  - The antiphospholipid antibody syndrome (APS) is defined by widespread arterial
      and venous thromboses associated with elevated plasma levels of antiphospholipid
      antibodies (APLA). The primary antiphospholipid antibody syndrome (PAPS) appear
      to be a fairly homogeneous disease, and HLA, family and other studies provide new
      insights into this cause of thrombosis and vascular disease. We describe two
      patients with PAPS (lupus anticoagulant positive), whose family members were
      analyzed for clinical and laboratory abnormalities associated with APS. Familial
      screening seems to be important, in order to prevent the thrombotic events. Low
      dose aspirin is the first line treatment in asymptomatic subjects with APLA,
      previous or present thrombosis requiring long-term, possibly life-long
      anticoagulation.

PMID- 11845464
TI  - Antitetanus and antidiphtheria immunity in newborns.
AB  - The level of antitetanus and antidiphtheria immunity was evaluated in 280 pairs
      (mother-newborn) and in 56 pairs where mothers (aged 19-26 yrs.) were vaccinated
      in the 7th month of pregnancy with an adsorbed tetanus vaccine dose. The results
      revealed a high antitetanus immunity level both in mothers and newborns (93.57%
      and 92.85% respectively) and a low antidiphtheria protection level (79.64% and
      77.14%). Immunization of pregnant women ensures a 100% passive protection of
      newborns against tetanus before administration of the first vaccine doses. The
      data obtained also proved that placental transfer of the specific circulating
      antibodies was high (98.58% and 95% for diphtheria). The high percentage of
      newborns susceptible to diphtheria toxinfection points to the need to immunize
      mothers-to-be with low combined diphthero-tetanus (d-T) vaccine doses and to
      closely observe vaccination programme (Ministry of Health) of children with
      combined diphthero-tetanus-pertussis vaccine (CDTPV) at an early age (two
      months).

PMID- 11845465
TI  - Leptospirotic etiology in pulmonary and upper respiratory tract pathology.
AB  - A number of 3,200 febrile patients who presented upon admission to hospital
      primary pulmonary or upper respiratory tract impairment either as single forms of
      manifestation or associated to other syndromes were tested. The cases were
      screened by the rapid slide agglutination reaction with heat inactivated Patoc
      antigen and leptospirotic etiology was confirmed by the ultramicroscopic
      agglutination reaction with 18 live circulating pathogenic antigens. 64
      leptospirosis cases with pulmonary impairment were confirmed and in 52 cases the
      upper respiratory tract was involved. Particular aspects of leptospirosis with
      pulmonary impairment: 71.8% of cases had a clinical diagnosis of interstitial
      pneumonia; 89% of cases presented important chest x-ray modifications; in an
      approximately equal number of cases the pulmonary involvement was the single
      manifestation or was associated with other syndromes; icterohaemorrhagiae, wolffi
      and pomona were the frequently encountered infecting serotypes. Particular
      aspects for leptospirosis involving the upper respiratory tract: 84.6% of cases
      had a clinical diagnosis of acute rhino-pharyngotracheitis; in 86.5% of cases the
      upper respiratory tract impairment was the single feature; the infecting
      serotypes were in decreasing order of frequency as follows: icterohaemorrhagiae,
      pomona, wolffi, canicola, grippotyphosa.

PMID- 11845466
TI  - The relevance of paternity analysis in Romanian population using the D1S80 locus.
AB  - At present, DNA fingerprinting for human identification and paternity testing is
      a necessary and usual procedure. D1S80 is one of the best known polymorphic loci
      showing a VNTR, and exhibiting a high heterozygosity. This genetic locus, with a
      Tsp 509 I polymorphism of its 5' flanking sequence (1, 9), have been successfully
      amplified from human genomic DNA isolated from blood. The Tsp 509 I polymorphism
      was detected by restriction after PCR amplification. We tested the relevance of
      paternity analysis using the D1S80 locus considering the allele frequency
      distribution characteristic for our country. Paternal and maternal bands were
      compared with the children's DNA patterns. Our data include a comparison between
      D1S80 alleles amplified from mother, child and the supposed father for three
      tested families. This study was the first of this type made in Romania. We
      concluded a good power of discrimination and exclusion for this locus. It can be
      used successfully in the case of subtypes with low frequencies, and this is
      frequent for our population because of the high heterozygosity of D1S80 subtypes
      in Romanian population. We recommend the D1S80 use for exclusion paternity tests
      in Romanian population, as a very useful molecular tool, but we also recommend a
      complete set of molecular markers for confirmation paternity test in the same
      population.

PMID- 11845467
TI  - Malaria in the whole world and in Romania.
AB  - Malaria is the world's most important tropical parasitic disease. Malaria is a
      public health problem today in more than 90 countries. Worldwide prevalence of
      the disease is estimated to be in the order of 300-500 million clinical cases
      each year. Malaria is endemic in a total of 101 countries and territories. In
      Romania, malaria does not represent an important public health problem. In 1999,
      there were reported a total number of 32 malaria cases in Romanian people. 78%
      from these recognized as etiological agent Pl. falciparum. The malaria cases
      imported from Turkey (5) have had as etiological agent Pl. vivax. The most
      affected age group is between 21-50 years and a distribution by profession shows
      that sailor personnel accounts for 65.6% of all cases. Africa remains the most
      important endemic region from where the malaria cases in Romanian people are
      imported. An adequate chemoprophylaxis is not, yet, easy to obtain for Romanian
      people who are travelling abroad in endemic countries because of the lack of
      specific drugs (especially for resistant forms of Pl. falciparum). Even if the
      Romanian Ministry of Health had elaborated orders regarding malaria and
      Cloroquine is the usual drug administered, as chemoprophylaxis, to Romanian
      people who travel abroad, in each year in our country appears around 30-60
      imported malaria cases. That is the cause why Romanian Ministry of Health wants
      to solve this problem which is the major cause of the malaria cases in Romanian
      people.

PMID- 11845468
TI  - Complex compounds of Pd(II), Pt(II), Ni(II), Hg(II) and Cu(I) with 1-benzylidene
      2-phenazinoylhydrazine.
AB  - Synthesis and physical-chemistry characterization of five new genuine complex
      compounds of 1-Benzylidine-2-phenazinoylhydrazine with Pd(II), Pt(II), Ni(II),
      Hg(II) and Cu(I) are presented. The chemical structure for these complexes is
      suggested by the elemental chemical analysis, molecular mass measurements,
      electric conductivities as well as by IR and UV-VIS spectra. The metal:ligand
      molar ratio is found 1:1, the obtained complexes belonging to the square planar
      geometry D4h.

PMID- 11845469
TI  - Differentiation of Shigella strains by plasmid profile analysis, serotyping and
      phage typing.
AB  - Ninety-one Shigella flexneri and 29 Shigella sonnei strains isolated during 1994
      from sporadic cases of shigellosis and healthy carriers were analyzed for plasmid
      profile in order to compare the discriminating ability of this method with that
      of serotyping and phage typing. Our study revealed 10 plasmid profiles (PP) among
      S. sonnei strains. A total of 26 out of 29 (89%) S. sonnei isolates could be
      placed into two phage types (type 1 and 20) comprising four PP for phage type 1
      and seven PP for type 20, respectively. Twenty-three different PP were identified
      among S. flexneri strains. Each serotype was associated with a specific
      predominant plasmid profile, except serotype 2a. This serotype, the most
      frequently isolated in Romania, was still rather homogeneous: 33 out of 39
      isolates belonged to phage type 125, 27 of which could be placed into two related
      PP (F10 and F17). Comparison of plasmid patterns of epidemiologically independent
      S. flexneri serotype 2a isolates with those exhibited by 45 serotype 2a isolates
      associated to six independent outbreaks revealed the same homogeneity. Thirty
      eight strains, representing 4 of 6 outbreaks, had F10 and F17 plasmid patterns.
      The discrimination indices (D) for plasmid profile analysis alone (D = 0.890) and
      for the combination of serotyping and phage typing (D = 0.841) indicate that both
      typing systems have a nearly similar ability of discriminating among S. flexneri
      strains. By combining the results of the three typing methods, a total of 42
      types are distinguished and the D value is 0.942. Our data suggest that plasmid
      profile analysis can complement phenotyping methods resulting in a degree of
      discrimination that cannot be achieved by either system alone.

PMID- 11845470
TI  - Ultrastructural changes induced in Walker carcinosarcoma by treatment with
      dihematoporphyrin ester and light in animals with diabetes mellitus.
AB  - The purpose of this study was to evaluate by electron microscopy the tumoral fine
      structure changes induced by photodynamic therapy (PDT) in diabetic animals.
      Walker -256 carcinosarcoma harvested from animals with/without diabetes mellitus
      exposed to PDT (Photofrin II/5 mg/kg and 24 hrs later He-Ne laser
      irradiation/632.8 nm; 10 mW) and examined by electron microscopy showed different
      degrees of lesions in the nucleus and cytoplasmic fine structure. The
      ultrastructural changes induced by PDT in animals with diabetes mellitus bearing
      carcinosarcoma are characterized by: lysis of chromatin situated on the central
      zone of nucleus; swelling and vacuolization of mitochondria; formation of
      phagosome--like structures; myelin figures; degenerescence and disappearance of
      cytoplasmic organelles. Summing up, the data presented in this work demonstrate
      that the exposure to three doses of PDT produces changes in tumoral fine
      structure, increases survival rate and reduces incidence of carcinosarcoma in
      rats with diabetes mellitus.

PMID- 11845471
TI  - Intestinal parasites infestation and anemia in primary school children in Gaza
      Governorates--Palestine.
AB  - A comparative study was carried out to identify the prevalence of anemia,
      nutritional indices and intestinal parasitic infestation in primary school
      children. The target population included 209 pupils aged 6-11 years, attending
      schools in two areas, Rimal area (urban) and Jabalia village (rural), in Gaza
      Governorates. Prevalence of intestinal parasites was high in Jabalia village
      (more than 53%) in comparison to Rimal area (33%). The main intestinal parasites
      were Entamoeba histolytica, Giardia intestinalis and Ascaris lumbricoides.
      Polyparasitism frequency is higher especially in rural area. In both areas anemia
      showed a high prevalence in children due to malnutrition and intestinal parasitic
      diseases. There was no association between intestinal parasitic infestation and
      children growth, but there was association between anemia and intestinal
      parasitic infestation in children, particularly in rural area. The correlation
      between anemia and mixed infestation reaches a highly significant level.

PMID- 11845472
TI  - The presence of some yeasts species in occupational dermatitis.
AB  - The samples of skin lesions were collected from forearms, palms and phalanges of
      ten females working in a manufacturing section (clothes tailoring and assemblage)
      using imported textiles. The samples were examined for bacteriological and
      mycotic flora by using classical methods. The textile fragments of 1-2 square
      centimeters from four samples were investigated using the same classical methods.
      The gauze fragments were used as toxic negative control samples. In 6 out of 10
      samples from cutaneous lesions, Candida albicans was isolated and in 5 samples
      Rhodotorula species was identified. The yeasts species were identified by
      cultural and biochemical characteristics. All C. albicans strains were positive
      for the germ tube test and produced spherical chlamydospores on corn meal agar.
      The Rhodotorula strains grew on Sabouraud agar pure orange-red pigmented and
      mucoid colonies of 2-3 mm diameter. The textile samples incubated on blood--agar
      (10% sheep blood) demonstrated a high toxic activity producing a surrounding beta
      hemolysis area of 3-5 cm. This lysis of the sheep red cell was caused by an
      unidentified chemical agent. In our cases, dermatites were associated with
      chemical and yeasts agents. The chemical agents irritated and made the derma
      sensitive, favouring C. albicans and Rhodotorula species multiplication.

PMID- 11845473
TI  - A therapeutical outlook in "infectious" bronchial asthma.
AB  - Chronic bronchial asthma seems to be generated by abnormal functions of PMNs and
      eosinophils stimulated by local bacterial flora. Once stimulated, they release
      uncontrolled excessive amounts of ROI and various soluble mediators. These are
      the expression of disorders in the synthesis of SOD, catalase and other enzymes
      by PMNs and an excessive production of the so-called anti-inflammatory Th2 type
      cytokines, mainly IL-4 and IL-5 to the detriment of IFN gamma and other Th1 type
      cytokines. Treatment consisting of autovaccines obtained from local flora
      associated with immunomodulators instead of antibiotics or glucocorticoids proved
      to be beneficial for patients.

PMID- 11845474
TI  - The migratory and phagocytic activity of polymorphonuclear leukocytes in
      rheumatoid arthritis and osteoarthritis patients.
AB  - Polymorphonuclear neutrophils (PMN) play a central role in the elimination of
      most extracellular pathogenic microorganisms and any impairment of their
      functions therefore predisposes to defect immune defence. We investigated the
      migratory and phagocytic functions of the PMNs isolated from peripheral blood and
      synovial fluid of patients with rheumatoid arthritis (RA) and osteoarthritis
      (OA). The results suggest that in RA the number and the migratory but not
      phagocytic capacity of synovial fluid (SF) neutrophils were enhanced, while in OA
      they were significantly decreased in synovial fluid cells comparatively with
      peripheral blood (PB). The migratory function of both PB and SF cells from RA
      patients was increased comparatively with that of the cells from OA patients. We
      found the different abnormal functions in synovial fluid neutrophils from RA and
      OA patients. These results may help to elucidate the underlying mechanism which
      leads to severe joint destruction and different susceptibility to infectious
      diseases in patients with rheumatic disorders.

PMID- 11845475
TI  - Investigation of the results obtained following repeated boosters with Di-Te
      vaccine in HIV positive children.
AB  - The paper is an attempt to study the effect of repeated boosters with Di-Te
      vaccine in positive children. The efficacy of their administration (vaccinal
      coverage degree, level of secreted antitoxins, the persistency of the immune
      response) and their influence upon the subsequent evolution of HIV infection are
      investigated.

PMID- 11845476
TI  - Interactions between listeriae and lectins.
AB  - Interactions between members of the genus Listeria and lectins are described. L.
      monocytogenes was shown to be heterogenous with respect to agglutination by
      lectins. L. monocytogenes serotype 4b had a pattern of lectin binding distinct
      from the other listeriae. Titration of the listeriae with lectins proved to be
      useful in further distinguishing serotype 4b. The results show that lectins may
      provide useful probes as diagnostic reagents for listeriae.

PMID- 11845477
TI  - The frequency of in vitro resistance to fluoroquinolones among clinical isolates
      of Escherichia coli.
AB  - The aim of this study was to investigate the activity of new quinolones against
      clinical isolates of E. coli, obtained from hospitalized patients between 1999
      2000, in Eastern Romania. We tested 411 strains, isolated from urine.
      Susceptibility of the isolates to norfloxacin, ciprofloxacin, nalidixic acid and
      ofloxacin was performed using the dilution method in Mueller-Hinton agar.
      Susceptibility was reported using the NCCLS breakpoints. Minimum inhibitory
      concentration (MIC) was defined as the lowest concentration of antimicrobials
      that inhibited growth of the bacteria. Based on MIC breakpoints for defining
      susceptibility, between 12.4-13.7% of isolates were resistant to modern
      quinolones. Resistance to nalidixic acid significantly diminished the clinical
      use: level of the susceptible strains was only 12.9%.

PMID- 11845478
TI  - Mercury resistance among clinical isolates of Escherichia coli.
AB  - The use of organomercurials in liquid detergents and disinfectants promoted
      resistance to mercury among bacteria. Dental amalgam and industries using mercury
      are the main source of human exposure to mercury vapor. Release of mercury from
      dental amalgam contributes to the enrichment of the intestinal flora with mercury
      resistance plasmids which may be associated with antibiotic resistance. The aim
      of our study was to evaluate the frequency of E. coli strains resistant to
      mercury and other antimicrobial agents currently used in therapy. The bacterial
      mercury and ampicillin, cephalexin, cefotaxime, gentamicin, tetracycline and
      chloramphenicol resistance was tested against 363 E. coli strains obtained from
      faeces and urine between 1999-2000. According to the guidelines suggested by
      NCCLS (1998), minimum inhibitory concentrations (MICs) were determined on Mueller
      Hinton agar, using the dilution technique with an inoculum of about 10(5) CFU.
      The MICs were read after 18 h incubation at 37 degrees C as the lowest
      concentration that inhibited the development of visible growth. Plasmids in
      enterobacteria may carry genes encoding resistance to both mercury and
      antibiotics. Among the tested E. coli strains, mercury resistance rose to 29.2%.
      Mercury resistance in E. coli is significantly linked to multiresistance to
      antimicrobial agents. Between 91.5-23.6 of mercury chloride resistant isolates
      were also resistant to the tested antibiotics. The increased use of non
      antibiotic antimicrobial agents is a possible selection factor for antibiotic
      resistant strains in clinical and domestic environments.

PMID- 11845479
TI  - Molecular characterization of Penicillium expansum MUCL mutants.
AB  - The modern biomolecular analysis of DNA was carried out to determine the identity
      of Penicillium expansum MUCL V1-V9 Variants with parental strain of Penicillium
      expansum MUCL 29412 and to compare the results with Penicillium verrucosum, a
      related species. The extracted DNAs were fragmented by digestion with restriction
      endonuclease Hind III and the fragments were separated by agarose gel
      electrophoresis. The DNAs were then denaturated in the gel after partial
      depurination with dilute acid and were transferred to a nylon membrane. The
      membrane was incubated with 32P-labeled probe, which was a DNA having a base
      sequence complementary to the DNA that was to be detected on the filter. The
      hybridization of the restriction fragments was performed for a highly qualitative
      comparison of the digested fragments. The analysis of the DNA profile, the most
      important stage in DNA identity testing, confirms the identity of the DNA for all
      strains of Penicillium expansum MUCL, except for V5 Variant.

PMID- 11845480
TI  - Molecular subtyping of group A streptococcal strains based on virulence regulon
      polymorphism.
AB  - A total of 64 Streptococcus pyogenes isolates included in a previous study
      (Shundi et al., 2000) were further analyzed by Vir typing. Vir typing is based on
      restriction fragment length polymorphism (RFLP) analysis of a 4- to 8-kb
      pathogenicity island (vir regulon) encoding emm and other virulence genes. As all
      our isolates contained a single vir regulon, the stoichiometric yield of
      restriction fragments avoided ambiguities in interpretation of results. By using
      both HaeIII and HinfI restriction endonucleases to generate RFLP profiles, the 64
      GAS isolates were distributed among 22 Hae- and 26 Hinf-Vir types respectively.

PMID- 11845481
TI  - A revised bibliography of the mosquitoes in Romania.

PMID- 11845482
TI  - Anticoagulation in continuous renal replacement therapy.
AB  - Continuous renal replacement therapy (CRRT) is a specialized intervention that is
      managed largely by critical care nurses who are educated in the theoretical and
      practical aspects of the therapy. CRRT is most commonly indicated for
      hemodynamically unstable patients who have acute renal failure and a narrow
      margin of tolerance for the rapid fluid shifts associated with traditional
      dialysis. Although the utilization of CRRT in the critical care setting is
      becoming more widespread, numerous factors need to be considered before therapy
      is initiated. The use of anticoagulation is a concern because of the associated
      risk of bleeding and thrombocytopenia. Nurses at the bedside must be expert in
      both managing CRRT and assisting in identifying patients who may be at potential
      risk when this form of treatment is in place. An overview of possible
      anticoagulants for use in CRRT is outlined in this article.

PMID- 11845483
TI  - Therapeutic plasma exchange.
AB  - The improvement in design and biocompatibility of continuous renal replacement
      therapy equipment has made it possible to perform therapeutic plasma exchange
      (TPE) in the intensive care unit. The purpose of this article is to outline the
      general principles of apheresis, including a historical perspective, current
      indications, and complications. Replacement fluid, membrane filtration,
      anticoagulation, and vascular access will be presented. A summary of the nursing
      care associated with TPE, potential complications, and methods to reduce the risk
      of their occurrence are summarized.

PMID- 11845484
TI  - Cost analysis of an intensive home follow-up program for first-time post
      myocardial infarction patients and their families.
AB  - OBJECTIVE: The general goal of this research was to determine the effectiveness
      of a home follow-up program in order to acquire guidance in how to plan the
      future structure and contents of post-myocardial infarction (MI) patients' care
      and rehabilitation. The specific aim of this study was to evaluate the cost
      effectiveness of the program in reducing the rate of rehospitalization of first
      time post-MI patients when measured at six weeks and six months post-discharge.
      HYPOTHESIS: The supportive-educative home follow-up program will prove to be cost
      effective by indicating an inverse correlation with the cost of post-MI patients
      being rehospitalized for unplanned and preventable diagnoses. DESIGN AND SETTING:
      Cost analysis, using data from a one year randomized control clinical trial
      conducted in a small urban hospital in eastern Canada. An experimental post test
      only control group design, including the process of randomization, was used in
      this study. SUBJECTS: 62 people admitted with a diagnosis of a first-time acute
      MI during a one-year period with no co-morbidity likely to affect rehabilitation.
      MAIN OUTCOME MEASURES: Health care costs. RESULTS: Early supportive home follow
      up reduced inpatient rehospitalization by more than half (three
      rehospitalizations vs seven rehospitalizations) and reduced the average length of
      stay (five days vs seven days). Cost analysis demonstrated that intense home
      follow-up in the time immediately following patient discharge could still produce
      cost savings to the health care system. CONCLUSION: Intensive home follow-up
      provided a cost-effective alternative to traditional cardiac rehabilitation
      programs; however, a larger study is required to assess the generalizability of
      the results and long-term cost effectiveness.

PMID- 11845485
TI  - Coping with a heightened level of stress.
AB  - Nurses are responsible for their own health. Knowledge about stress will increase
      ones repertoire of intervention possibilities. To really rev up your engine,
      address the energy drains, and incorporate simple life-style changes, like proper
      exercise, adequate nutrition, appropriate sleep, and a positive attitude. Take
      time for your spiritual life and emotional contentedness. Refueling your body
      will increase your day-to-day vigor and overall health.

PMID- 11845487
TI  - Management of medicines in hospitals is very poor.

PMID- 11845486
TI  - Can stress make you lose your hair?
AB  - Many individuals are frightened by hair loss and are hesitant to speak about it.
      Many are unaware that stressors can causes hair loss and that hair care practices
      and habits can aggravate a hair loss situation. Intervention by the nurse in
      encouraging a person to have an adequate assessment and work-up can facilitate an
      accurate diagnosis. Supportive and appropriate therapy can then be arranged. The
      hair tells a story and can be associated with good health.

PMID- 11845488
TI  - 'Irrational' prescription system must be changed.

PMID- 11845490
TI  - Racism provokes mental illness.

PMID- 11845489
TI  - Modernization of prison healthcare necessary to meet inmates' needs.

PMID- 11845491
TI  - Will health care change for the better in 2002?

PMID- 11845492
TI  - [Effective hygiene measures lower risk].

PMID- 11845493
TI  - [Without pain and trauma].

PMID- 11845494
TI  - ["We must open the sluice to the operating room" (interview by Uti Luthi)].

PMID- 11845495
TI  - [How errors become learning opportunities].

PMID- 11845496
TI  - [Transition and future in continuing education].

PMID- 11845498
TI  - [Decisions].

PMID- 11845497
TI  - ["I am nailed to the bed"].

PMID- 11845499
TI  - [What is the motive of women?].

PMID- 11845500
TI  - [Primary prevention].

PMID- 11845501
TI  - [Urinary incontinence. Revision of representations].

PMID- 11845502
TI  - [Making the body talk].

PMID- 11845503
TI  - [Making the transition with smoothness].

PMID- 11845504
TI  - ["If no one hears us, perhaps it is because we have nothing to say!"].

PMID- 11845505
TI  - [Strengths and weaknesses in nursing care].

PMID- 11845507
TI  - [Many open questions].

PMID- 11845508
TI  - [Self-care promotes well-being in dialysis patients].

PMID- 11845506
TI  - [Professional reintegration in geriatrics].

PMID- 11845510
TI  - The effectiveness of a cardiac rehabilitation program on self-efficacy and
      exercise tolerance.
AB  - This study evaluates the effectiveness of graded physical exercise on self
      efficacy and exercise tolerance among a group of cardiac patients (N = 43). These
      patients were aged from 41 years to 82 years (mean age = 63.5 years, SD = 10.0
      years). Results of the study show that efficacy of physical activity was
      significantly associated with exercise tolerance. After a 3-month rehabilitation
      with graded physical exercise, both efficacy of activity and exercise tolerance
      were significantly enhanced. The enhancement was relatively independent of
      patients' gender, age, education, and diagnostic category. Limitations of the
      study are discussed and future research suggested.

PMID- 11845509
TI  - [A diverse perspective of viewing the world].

PMID- 11845511
TI  - The contribution of chronic illness to acceptance of death in hospitalized
      patients.
AB  - This pilot study explored acceptance of death in the chronically ill. It was
      hypothesized that chronic illness would be a positive predictor of premature
      acceptance of death. Acceptance of death, if premature, may lead to untimely
      acquiescence to death, making people less likely to seek medical care and
      practice preventive health behaviors. A correlational design was used to explore
      the relationship between chronic illness and acceptance of death, controlling for
      age. Data were collected on death acceptance using the revised version of the
      Life Attitude Profile. Number of chronic illnesses was obtained from self-report
      and a review of the medical record in a sample of 76 hospitalized individuals.
      The number of chronic illnesses was significantly and positively associated with
      death acceptance, but age was not. The model explained only 5.2% of the variance
      in death acceptance, however. Chronic illness is clearly only one of many factors
      stimulating individuals to ponder death earlier than expected. Nurses need to be
      alert to the possibility that individuals with multiple chronic illnesses may be
      prematurely acquiescing to death. If acquiescence causes failure to participate
      in care, it could potentially exacerbate chronic conditions unnecessarily.

PMID- 11845512
TI  - Nurses' strategies when providing for patients' aesthetic needs. Personal
      experiences of aesthetic means of expression.
AB  - The present study was conducted at five hospitals in Sweden. Data were collected
      by a random procedure from registered nurses (N = 165) in face-to-face
      interviews. The study reports on how and why nurses provide for patients'
      aesthetic needs. Open substantive coding of each interview fractured the data.
      The category of good for the patient was identified in the following nurses"
      statements: "The patient became relaxed" and "It distracted the patient from her
      pain." Regarding the question about how nurses provide for the patients'
      aesthetic needs, they did it in a nonactive manner. They used the basic service
      available at the wards. It could be concluded that although nurses show concern
      for patients' aesthetic needs, there is still more to be learned in this area of
      research. Nurses need to be encouraged to actively incorporate aesthetic means of
      expression in nursing practice.

PMID- 11845513
TI  - Social support, personal control, and psychosocial recovery following heart
      transplantation.
AB  - To study the influence of psychosocial resources on psychological recovery after
      heart transplantation, 28 patients were surveyed during their hospitalization
      after transplant surgery and 6 months posttransplantation. Scales from the Coping
      With Serious Illness Battery were used to measure psychosocial resources (social
      support and personal control) and psychological and functional outcomes.
      Psychosocial resources assessed during hospitalization were associated with
      recovery outcomes at 6 months posttransplantation. Personal control was
      positively correlated with optimism, well-being, and satisfaction with life (r =
      .41 to .49) and negatively correlated with anger (r = -.57) and depression (r = 
      .52). Social support network helpfulness and attachment with others were
      correlated with psychological outcomes (r = .41 to .59) and functional outcome (r
      = .42 to .47). Efforts directed toward enhancing perceptions of personal control,
      social support network helpfulness, and attachment may be useful for promoting
      psychosocial recovery.

PMID- 11845514
TI  - Evidence-based practice: the need for leadership.

PMID- 11845515
TI  - The effect of social support on exercise behavior in older adults.
AB  - The purpose of this study was to test the relationship among social supports
      related to exercise (family, friends, and expert support), self-efficacy
      expectations, outcome expectations, and exercise behavior in a sample of older
      adults living in a continuing care retirement community. The sample included 74
      older adults with a mean age of 85.6 +/- 5.5. Path analysis using Amos 4.0 was
      done. The model fit the data (chi-square = 4.6, df = 3, p = .21, normed fit index
      of .99, relative fit index of .98, and root mean square error of approximation of
      .08) and explained 53% of the variance in exercise behavior. Five of the seven
      hypothesized paths in the model were statistically significant. Friend support
      indirectly influenced exercise through self-efficacy and outcome expectations.
      This suggests interventions to improve exercise behavior in older adults should
      incorporate social supports to strengthen self-efficacy and outcome expectations
      related to exercise.

PMID- 11845516
TI  - Characteristics of nausea reported by HIV-infected patients initiating
      combination antiretroviral regimens.
AB  - Reliable data on the incidence and severity of nausea accompanying combination
      antiretroviral therapies is lacking. A prospective time series design was used to
      assess the rate, severity, and distress of nausea in a cohort of 75 HIV-positive
      patients who were beginning or changing a combination of two or more
      antiretroviral medications. Data were collected via telephone at weekly intervals
      for 12 weeks. The rate of nausea across regimens was greatest at Week 1 (39%) and
      declined progressively over time. By Week 12, the rate of nausea was only 5%.
      Severity of nausea was ranked as moderate or severe by a substantial proportion
      of patients through Week 10; however, nausea severity and distress were also
      found to diminish over time. The nausea associated with combination
      antiretroviral therapy is quite common and may adversely affect medication
      adherence. Findings indicate that clinicians should consider initiating
      interventions for management of antiretroviral-related nausea at baseline.

PMID- 11845517
TI  - A quantitative use of the NIDCAP tool. The effect of gender and race on very
      preterm neonates' behavior.
AB  - The purpose of this study was to demonstrate how the check sheet of the Newborn
      Individualized Developmental Care and Assessment Program (NIDCAP) can be
      quantified and used in research. Using the quantified NIDCAP measures, the
      hypothesis that Caucasian male infants are less behaviorally competent while in a
      neonatal intensive care unit (NICU) was explored. Participants included 42 very
      preterm NICU infants. Eighty-five NIDCAP behaviors were quantified into scores
      ranging from 0 to 1, indicating the percentage of time each behavior was
      observed. Multivariate analyses were used in grouping the 85 NIDCAP behaviors
      into three subsystems of functioning. The hypothesis that Caucasian male infants
      were less competent was not supported; neither were gender differences found.
      Contrary to this hypothesis, African American infants were identified as more
      vulnerable on several behaviors. NIDCAP assessments were easily quantified. Once
      the entire NIDCAP exam has been quantified, practice applications may involve
      automated development of individualized care plans.

PMID- 11845518
TI  - [Bacteriologic aspects of Haemophilus influenzae meningitis in children at the
      Central University Hospital of Treichville].
AB  - The object of our study was to contribute to the knowledge of the epidemiology
      and bacteriology of Haemophilus influenzae so as to ensure better treatment of
      patients consulting the Treichville Teaching Hospital. In the bacteriology
      laboratory of that hospital, between January 1996 and December 1999, we diagnosed
      by culture and/or soluble antigen, 203 cases of Haemophilus influenzae in
      children. We observed that biovar IV was dominant (49.7) amongst the 163 (80.3%)
      positive cultures. Serovar b was the most frequent capsular type found 189/203
      (93%). Of the 203 specimens, the frequency of other capsular forms was e 9/203
      (4.5%), f 3/203 (1.5%), c 2/203 (1%). Resistance to ampicillin is currently
      estimated at 39.9%, whereas resistance to chloramphenicol is estimated at 5.5%.

PMID- 11845519
TI  - [Peritoneal tuberculosis and HIV infection. Reflection apropos of 22 cases at the
      National Hospital of Bobo Dioulasso].
AB  - Peritonitis tuberculosis is still a frequently encountered pathology in our
      hospital. Since the AIDS pandemic, cases of peritonitis tuberculosis present
      increasingly atypical characteristics, largely diverging from classical
      descriptions. The authors report on 22 cases of peritonitis tuberculosis
      associated with HIV infection. The study was carried out from June 1997 to
      December 1999 in the National Hospital Centre Souro SANOU of the Bobo Dioulasso
      internal office. It concerned 10 women and 12 men of a mean age of 37.9 years.
      The sex-ratio was 1.2 in favour of men. Diagnosis was established by laparoscopy.
      Peritonitis tuberculosis associated with HIV accounted for 78.5% of peritonitis
      tuberculosis cases. The clinical picture was dominated by isolated ascite (100%)
      associated with an oscillating high fever in 68.2% of cases. Negative results for
      IDR seemed to reflect poor prognosis. Response to treatment was slow but
      acceptable. The general prognosis was poor with a mortality rate of 18%.

PMID- 11845520
TI  - [Bacterial meningitis in Yaounde (Cameroon) in 1999-2000].
AB  - All cephalo-spinal fluid (CSF) samples sent to the Yaounde Pasteur Centre in
      Cameroon, between July 1999 and June 2000, were cultured and tested for soluble
      antigens. The percentage of positive samples was 10.4%. The main etiological
      agents detected were Streptococcus pneumoniae (56.2%), Haemophilus influenzae
      (18.5%) et Neisseria meningitidis (13.4%). Most of these cases of bacterial
      meningitis were children (86.7%). The susceptibility of the isolates to
      antibiotics was investigated. The streptococci and meningococci were mostly
      susceptible to beta-lactams, but the Gram-negative bacteria were not.
      Combinations of amino-penicillin and aminoside or chloramphenicol continue to be
      effective, as are third generation cephalosporins used alone. Meningococci appear
      to have emerged during the year 1999/2000, with 23 such isolates identified, of
      which 17 were serogroup A, subtype P1-9, clone III-1, which was responsible for
      the second pandemic. It should also be noted that 4 strains of N. meningitidis of
      serogroup W135 were isolated in Yaounde.

PMID- 11845521
TI  - Asymptomatic amoebic infection: Entamoeba histolytica or Entamoeba dispar? That
      is the question.
AB  - Two cases of amoebic infection were diagnosed in a heterosexual couple. The
      cases, a Frenchman with previous trips to various African countries and his
      sexual partner, a Cameroonese woman immigrant living outside the community, were
      both asymptomatic; the infection had been diagnosed by chance in the man at the
      time of his employment in a hospital kitchen. Based on what is known of the
      epidemiology of amoebic infection, it may be acquired and then transmitted within
      a couple via the indirect faecal-oral route or, in greater likelihood, by sexual
      practices. Both amoebic isolates were characterised by isoenzyme electrophoresis
      as non-pathogenic Entamoeba dispar, zymodemel. Other diagnostic tools, such as
      ELISA direct stool antigen detection tests and serological assays were employed,
      confirming the diagnosis of E. dispar infection. Given there are a number of
      asymptomatic cyst passers of Entamoeba histolytica, besides human carriers of
      saprophyte E. dispar, we stress the importance of applying, when possible,
      advanced protocols of diagnosis to distinguish the microscopically identical
      pathogenic species from the non-pathogenic one.

PMID- 11845522
TI  - [Localized tetanus in Abidjan: clinical and prognostic features (1976-1997)].
AB  - Localised tetanus, rarely described in Africa, was examined retrospectively in
      Abidjan, over a period of 22 years (1976-97). Forty-five patients--representing
      an incidence rate of 2% of tetanus cases--were reported in this time span. The
      mean age was 23 years, and none of the patients had had prior access to adequate
      immunoprophylaxis. Three clinical forms were observed: tetanus of the limbs (32
      cases, 71%), cephalic tetanus (11 cases, 25%), and abdominal tetanus (2 cases,
      4%). Infection had occurred via wounds of the limbs (38%), intramuscular
      injections (33%), craniofacial wounds (25%), and abdominal wounds (2%). No portal
      of entry was identified for 2% of the cases. 37 patients were cured (82%) of whom
      5 retained sequelae (11%). 7 deaths were observed (16%). In terms of prognosis,
      the only risk was secondary generalisation of tetanus (27%). CONCLUSION:
      Localised tetanus is far from being mild and incurs significant rates of
      sequelae. The only efficient treatment is immunisation-based prophylaxis.

PMID- 11845523
TI  - [Is manioc a diabetogenic factor? Apropos of a case of diabetes mellitus with a
      large consumption of crude manioc].
AB  - The case of a 24 year-old Comorian male patient consuming large amounts of cooked
      and uncooked cassava and suffering of malnutrition since his boyhood is reported.
      The patient presented a diabetes mellitus by chronic calcific pancreatitis with
      retinopathy and neuropathy. The protein deficiency associated with eating
      uncooked cassava may be recognised as a factor of calcific pancreatitis diabetes.
      Other factors might be associated such as the environment as well as
      immunological and genetic characteristics.

PMID- 11845524
TI  - [Diagnostic problems of expansive intracranial process in HIV infected patients
      of the Bobo-Dioulasso Central Hospital (Burkina Faso)].
AB  - In HIV infection, cerebral focal lesions are relatively frequent and raise many
      kinds of diagnostic problems. In tropical practice, neuroradiology is scarcely
      available and necropsy is still not developed. Therefore, diagnosis of
      intracerebral masses among patients is not easily performed. We examined a total
      of 72 patients who presented over a 3-year period. Patients were allocated to
      presumed diagnostic categories of toxoplasma encephalitis (TE), primary central
      nervous system lymphoma (PCNSL) or progressive multifocal leukoencephalopathy
      (PML), based on clinical and therapeutic criteria. In an internal medicine ward,
      we examined 72 suspected cases of intracerebral masses in a sample of 43 males
      (60%) and 29 females (40%). The average age was 38 years with extremes ranging
      from 21 to 72 years. Because of diagnostic problems, the presumption of a TE has
      been retained in 54 cases (75% of the sample) owing to the efficiency of the
      treatment of antitoxoplasmic proof. As for the other intracerebral masses,
      despite insufficient diagnostic means, the assumption of PCNSL was made for 8
      cases and PML for 6 cases on the basis of evolutional criteria. In 4 cases, no
      diagnosis could be retained because of insufficient diagnostic means and
      treatment failure. Since brain tomodensitometry and brain biopsy are not
      available, treatment of toxoplasmosis has to be systematically set up whenever
      there is a presumption of intracerebral masses among patients with HIV infection.
      It is only in case of failure of this treatment that other hypotheses can be
      contemplated, especially as they are not entirely reliable.

PMID- 11845525
TI  - [Spontaneous ascitic infection in cirrhotic Africans. Descriptive study apropos
      of 12 cases].
AB  - BACKGROUND: Spontaneous ascitic infection (SAI) is a frequent and serious
      complication of cirrhosis. OBJECTIVE: In a retrospective study, the authors
      report clinical and biological data associated with SAI for cirrhotic patients in
      an African medical centre. METHODS: Twenty-two cirrhotic patients with ascites
      were included in a one-year study (November 1996 to October 1997). Clinical and
      biological data were obtained through medical files. FINDINGS: The mean age of
      the 22 cirrhotic patients with ascites (12 men, 10 women) was 48.9 years. Twelve
      cases of SAI were found. In a univariate analysis, the more frequent data in
      patients with SAI when compared to patients without SAI were: fever or
      hypothermia (91.7% versus 10%, p = 0.002), abdominal pain (83.3% versus 40%, p =
      0.046), cloudy ascitic fluid (66.7% versus 10%, p = 0.003), medium albuminemia
      (18.2 g/l versus 23 g/l, p = 0.02), medium prothrombin rate (42.8% versus 58.3%;
      p = 0.04) and ascitic fluid protein level < or = 10 g/l (91.7% versus 30%, p =
      0.01). The protein level in ascitic fluid cirrhotic patients was significantly
      lower in SAI than in patients without SAI (7.6 g/l versus 11 g/l; p = 0.005). In
      a multivariate analysis, protein levels in ascitic fluid were the only factor
      associated with SAI (p = 0.024).

PMID- 11845526
TI  - [Perihepatitis and HIV/AIDS infection. Apropos of 13 cases at the National
      Hospital of Bobo-Dioulasso].
AB  - Perihepatitis or Fitz-Hugh syndrome, peritonitis located in the right
      hypochondriasis (RH), is a relatively rare affectation. However, the HIV-AIDS
      pandemic has brought about the emergence and re-emergence of disease-states
      either uncommon or formerly on the decline as well as the appearance of
      opportunistic illness. We report the results of a retrospective study conducted
      in the National Hospital of Bobo-Dioulasso (Burkina-Faso) between 1 June 1997 and
      31 December 1999 in an effort to contribute to a wider vision of diseases
      associated with HIV-AIDS. We based our study on 130 laparoscopies carried out for
      unexplained pain linked to RH (with or without fever), as well as abdominal
      pelvian or diffuse abdominal pain. Thirteen cases (11 women, 2 men) of
      perihepatitis were diagnosed. The mean age for women and men was respectively
      31.4 and 39.5. HIV serology was systematically carried out for all patients and,
      in case of perihepatitis, cultures were taken. All patients were infected with
      HIV and some presented signs of AIDS according to the WHO classification. In
      clinical terms, a shalking pain for RH was noted for 5 patients, abdominal
      sensitivity in 8 cases as well as gynaecological anomalies: cul-de-sac moving
      pain (4 cases), leuchorrea (3 cases) and mucosic vulvovaginitis (1 case).
      Paraclinical tests revealed a slight hepatic cytolysis for only 3 patients (1.5
      N). 6 patients tested positive for Chlamydia trachomatis; the 7 others could not
      be tested, but this aetiology was assumed for evaluating the efficacy of the
      treatment under study. The high frequency of perihepatitis in these patients, all
      of whom were suffering from HIV-AIDS, and its presence in the 2 male cases,
      suggest that immunodepression is conducive to the appearance of this disease.

PMID- 11845527
TI  - [Pubertal development in girls with homozygote sickle cell disease. Apropos of 72
      cases].
AB  - We carried out a case-control study to investigate the sexual maturation of girls
      suffering from homozygous sickle cell disease: 72 cases aged 10 to 18 years were
      compared to 40 controls of the same age. We obtained the following results: In
      cases, there was a significant delay in signs of physical maturation; puffiness
      of the mammary glands at 14.4 years +/- 1 (as versus 12.4 years +/- 1.5 in
      controls); pubarche occurred at 14.2 years +/- 1. Menarche occurred on average at
      15.2 years +/- 1.6 (as versus 13.4 years +/- 1.4 for controls) and the lack of
      the menarche between the ages of 14 and 18 years was observed in 71% of cases as
      versus 10% of controls. At age 16, only 1% and 3% of cases were respectively at
      the stage of S5 and P5 as versus 40% for the controls. Thus, 37% of girls
      suffering from homozygous sickle cell disease were not sexually mature, whereas
      all controls had reached sexual maturation by the age of 14. In cases, weight
      remained low, and waist line and the body shape poorly developed in comparison to
      controls'. The examination by scanner of the pelvis of 20 girls suffering from
      homozygous sickle cell girls that in 25% of the cases, the ovaries of non mature
      girls were relatively small.

PMID- 11845528
TI  - [Tuberculosis, primary biliary cirrhosis and autoimmunity (apropos of a case in
      Tunisia)].
AB  - We report the case of a 70 year-old Tunisian patient who developed
      antimitochondrial antibodies and anti-ADN during urogenital tuberculosis with
      clinical and biological signs of primary biliary cirrhosis and systemic lupus
      erythematosus. We discuss the association of the three diseases and the
      etiopathogeny of the autoimmune mechanisms induced by Mycobacterium tuberculosis.

PMID- 11845529
TI  - [Breast diseases in young women of Niger: results of a campaign for self
      examination awareness in a nursing school].
AB  - In order to favour the early diagnosis of breast cancer, the authors used an
      original method consisting in teaching nurses about breast tumors and cancer, and
      especially about self-examination of the breasts. Subsequently, 73 patients aged
      under 24 years were admitted to our survey: 90 per cent had an understanding of
      risk factors and 97 per cent were practicing self-examination. In 21 cases,
      consultation was carried out for mastalgia and in 12 cases for esthetic and/or
      banal inflammatory lesions: 40 patients presented a lump in the breast.
      Sonography turned out to be a better method of examination than mammography in
      those young women presenting breast lesions. Following surgery, histological
      examination found that in the majority of cases the tumour was benign (fibrocyst
      or adenofibromas). We were surprised by medullary carcinoma in one case.

PMID- 11845530
TI  - [Ultrasonographic aspects of urinary schistosomiasis in children of the Dogon
      plateau and the Niger office; impact of praziquantel treatment].
AB  - Urinary bilharziasis is a parasitic infection responsible for vesical, urethral
      and renal lesions. The authors demonstrate the importance of ambulatory
      echography on a large scale and describe various echographic lesions. Vesical
      attacks occurred in 27% of the wall irregularity, 44% of the masses and polyps.
      Pyelic and urethral abnormalities occurred in 16.6% and 29.9% of cases
      respectively at the baseline in 1991. These prevalence rates decreased after
      seven years, in 1998. The authors discuss the utility of chemotherapy with
      praziquantel and the necessity of a periodical mass treatment in the areas with
      high bilharziasis endemicity in Mali.

PMID- 11845531
TI  - [Prevalence of serologic markers of the hepatitis B virus in pregnant women of
      Bamako, Mali].
AB  - A prospective study of the serological markers of hepatitis B virus (HBV)
      including hepatitis B virus surface antigen (HBsAg) and hepatitis B surface
      antibody (anti HBs) was conducted over 5 years in Bamako. The aims of this study
      were to assess the prevalence of HBsAg in pregnant women and to determine the
      risk of HBV infection for this population. The study involved 829 pregnant women
      for whom blood samples were collected after the first quarter of pregnancy. HBsAg
      and anti HBs were detected in all cases by radioimmunoassay. The prevalence of
      HBsAg and anti HBs in pregnant women was respectively 15.5% and 16.9%. This
      prevalence of HBsAg, higher than in the general population, points to the fact
      that pregnant women are a high risk group for hepatitis B infection. In addition,
      scarification and tattooing practices increase significantly the risk of
      infection by hepatitis B virus (OR = 2.03; 1.07 < OR < 3.82; chi 2 = 5.62; p:
      1%). Thus, we can presumably conclude that infants and new borns in such
      conditions are largely exposed to hepatitis B virus infection, even though
      hepatitis B core antibody and hepatitis B e antigen were not investigated for
      technical reasons. In conclusion, the authors believe that infants and new borns
      must be systematically immunised against hepatitis B virus infection in Bamako.

PMID- 11845532
TI  - [Hyperendemic loaiasis in the Tikar plain, shrub savanna region of Cameroon].
AB  - A survey on filariasis was conducted in the south-western part of the Adamaoua
      Province (Cameroon). In the Bankim district, located in the Tikar plain, the 10
      surveyed villages were all hyperendemic for loiasis. The prevalence of
      microfilaraemia in adults exceeded 50% in four communities, and 5.4% of the
      adults had microfilarial loads above 30,000 microfilariae per ml blood. In the
      Banyo district, which is contiguous but located on the Adamaoua Plateau, five of
      the six villages examined were hypoendemic for loiasis. The considerable levels
      of endemicity recorded in the Tikar Plain, a region of pre-forest shrub savanna,
      are probably due to the presence of forest-galleries, favourable to the biology
      of Chrysops. Regarding onchocerciasis, the most affected villages were located
      south of the Tikar Plain, near the Mbam River. The low prevalence of hydroceles
      suggests that lymphatic filariasis is not endemic in this study area.

PMID- 11845533
TI  - [Entomologic study of loaiasis transmission in the Lekie area (Cameroon)].
AB  - A number of cases of Loa encephalopathy have been recorded after ivermectin
      treatment in the Lekie Division, an area of degraded forest located in central
      Cameroon. An entomological study was carried out in a village of this region
      between May 1999 and April 2000 to determine whether the high microfilarial loads
      of Loa found in the population, which can exceed 10,000 microfilariae per ml of
      blood, were related to high densities of vector populations. The Chrysops
      collected at 10 catching stations, using hand nets, by persons standing by a wood
      fire, were dissected to evaluate their level of infection with Loa. The vectorial
      densities were three-fold higher in the forest stations than in those located
      near the habitations (2307 and 725 bites per man per year, respectively). These
      values are lower than those reported from similar studies in Cameroon, Congo and
      Gabon. Measurement of Chrysops densities does not seem to be an appropriate tool
      to evaluate the level of endemicity of loiasis, and to delineate the areas where
      there is a risk of post-ivermectin Loa encephalopathies.

PMID- 11845534
TI  - [Malarial vectors in French Guiana: study in an epidemic focus near Cayenne (1989
      1998)].
AB  - Malaria has long constituted a major public health problem for French Guyana,
      limiting its demographic and economic development. From 1949 to 1960, due to
      chemoprophylaxis and DDT spraying in houses, the number of malaria cases
      decreased markedly. After 1975, important migratory movements contributed to
      increasing the incidence of malaria. In 1989, numerous cases were observed when
      some 500 immigrants settled in a formerly uninhabited area, known as Cabassou BP
      134. It is located 7 km (S-E) from the main city of Cayenne and bordered by
      secondary forest and swamps. The entomological study initiated in 1990 included
      weekly biting-landing catches (3 hours) on human bait in houses from dusk onwards
      as well as locating breeding places around the settlement to collect larvae by
      dipping. Anopheles specimens were identified and the females dissected to detect
      infections by Plasmodium and also to determine the rate of parous specimens.
      Control measures included deltamethrin (15 mg/m2) and DDT (2 g/m2) spraying,
      every four months, of interior walls and thermal fogging of naled around the
      houses. Cold ULV aerosol of fenitrothion (500 ml/ha) was also used to treat the
      swamp borders. In April 1990, a health education programme was begun and in June,
      288 impregnated bednets (deltamethrin 15 mg/m2) were treated. From 1990 to 1998,
      1,588 (498 larvae + 1090 adults) Anopheles (Nyssorhynchus) were collected: An.
      aquasalis 797 (311 L + 486 A). An. braziliensis 139 (87 L + 52 A). An. darlingi
      652 (100 L + 552 A). No infected female was found among the 710 dissected. The
      number of malaria cases decreased abruptly in the fall of 1990 when An. darlingi
      disappeared and only one case due to P. vivax was detected between 1995 and 1998.
      An. darlingi (parous rate = 72%) appears to be the main if not the sole vector of
      malaria in this locality. As in the past, a focus of malaria appears when
      immigrants from endemic countries settle in a formerly uninhabited place where
      An. darlingi are breeding.

PMID- 11845535
TI  - [Craniocerebral trauma: epidemiologic aspects apropos of 234 cases collected from
      the emergency services of the Central University Hospital of Mahajanga].

PMID- 11845536
TI  - [Award of the Brumpt Prize 2000 to Jean-Antoine Rioux, February 14 2001 by the
      Society for Exotic Pathology].

PMID- 11845537
TI  - Basic life support cardiopulmonary resuscitation.
AB  - CPR represents the primary intervention used during cardiac arrest for
      maintaining perfusion and extending the potential resuscitation period. Effective
      CPR, however, requires careful attention to detail by the resuscitation team,
      including (1) effective control of the airway using manual maneuvers or airway
      adjuncts, (2) delivery of effective ventilation that assures adequate
      oxygenation, while reducing the chance for gastric inflation, and (3) chest
      compressions delivered at the appropriate depth and rate using a duty cycle of
      50% compression and 50% release. During the resuscitation effort team leaders
      should closely monitor the performance of CPR, rotate rescuers frequently to
      avoid fatigue, and provide continuous feedback based upon direct (transmitted
      pulse, chest rise) and indirect (end-tidal CO2) measures of effectiveness. A
      careful and measured approach to CPR performance, combined with a strong chain of
      survival, provides victims of cardiac arrest the best chance for survival.

PMID- 11845538
TI  - Acute ischemic syndromes. Early response.
AB  - The optimal treatment of patients with AIS depends on a well-run, integrated
      system of care involving patients and teams of health care professionals. It
      begins with patient education and extends to a method for accessing an efficient
      and effective EMS system. Medics must be well equipped and well trained to
      evaluate and begin initial treatment during prompt transport to an appropriate
      hospital. The role of out-of-hospital 12-lead ECGs and thrombolysis is reviewed
      and may be appropriate for some EMS systems. The initial evaluation and treatment
      in the ED goes on simultaneously and is a dynamic process. Prompt treatment with
      oxygen, nitroglycerin, morphine, and aspirin is indicated. Initial risk
      stratification is based on the first ECG, cardiac biomarkers, and the clinical
      history and physical exam. Disposition and further evaluation is individualized
      according to the initial work-up and risk assessment.

PMID- 11845539
TI  - Acute ischemic syndromes. Chest pain center concept.
AB  - CPCs have been developed to meet the clinical challenge posed by the diverse
      group of patients presenting to the ED with findings suggestive of a coronary
      event. Using a protocol-driven approach, high- and low-risk patients can be
      identified on presentation, facilitating urgent therapy in the former and triage
      of the latter to more deliberate management. Most CPCs focus on low-risk patients
      who are being increasingly managed by accelerated diagnostic protocols. These
      methods comprise systematic strategies that include innovative diagnostic
      approaches during a 6 to 12 hour period of observation with serial ECGs,
      continuous monitoring and cardiac biomarker measurements. A negative evaluation
      is usually followed by predischarge stress testing, and positive findings mandate
      admission. An essential aspect of the CPC strategy is continuity of care for
      patients with negative cardiac evaluations. Current data indicate that management
      of low-risk patients with chest pain in a CPC is safe accurate, and appears to be
      cost-effective.

PMID- 11845540
TI  - Defibrillation.
AB  - The field of defibrillation is one of the most rapidly advancing areas in
      resuscitation. Defibrillation is also one of the most promising interventions for
      achieving improved survival from cardiac arrest. The purpose of this article is
      to provide an overview of the science and clinical applications of
      defibrillation.

PMID- 11845541
TI  - The reperfusion era. Strategies for establishing or maintaining coronary patency.
AB  - Only 3 decades ago, controversy existed over the origin of the thrombus that
      occluded coronary arteries during myocardial infarction (MI). Then, the acute
      clinical angiographic studies of DeWood butterssed new pathological and
      experimental evidence that the thrombus was the proximate cause of MI and
      unstable angina. The remaining years of the 20th century saw an explosion of
      knowledge delineating a spectrum of related disorders now collectively called
      acute coronary syndromes (ACS). The clinician managing patients is confronted
      with an array of evidence as more than 75,000 patients worldwide have been
      randomized to clinical trials in ACS. This article reviews key pathophysiological
      concepts, presents an initial strategy for triage of patients, and summarizes
      evidence-based medicine guiding therapy for acute coronary lesions.

PMID- 11845542
TI  - Acute ischemic syndromes. Adjunctive therapy.
AB  - The acute coronary syndromes (ACS) represent a heterogeneous group of patients
      along a continuum of risk from unstable angina to non-ST-segment elevation
      myocardial infarction. ACS is a term that has been used to describe the
      constellation of clinical symptoms that represent acute myocardial ischemia. This
      article reviews the adjunctive medications that are used during emergency
      cardiovasculare care for the early management of patients experiencing the ACS.
      The adjunctive therapies are divided into early immediate treatment and then
      subsequent management in the acute care setting.

PMID- 11845543
TI  - Airway and ventilation management.
AB  - Airway management is fundamental to ACLS. Success with any airway device relies
      as much on the operator's experience and skill as on the device itself. The
      purpose of using an airway device is to provide a patent route for ventilating
      the lungs and to protect against pulmonary aspiration. Training should emphasize
      the importance of confirming that the airway device is positioned correctly and
      that the lungs can be ventilated effectively. If airway intervention is to have a
      positive effect on outcome, the choice of airway device is less important than
      thorough training, ongoing experience and review, and close attention to
      complications. Regardless of whether a provider chooses to use the LMA, the
      combitube, or the tracheal tube, providers must be familiar with more than one
      method of airway management because of the possibility of failure to insert or
      ventilate with their primary airway device of choice.

PMID- 11845544
TI  - Circulatory adjuncts. Newer methods of cardiopulmonary resuscitation.
AB  - Principles of cardiovascular physiology tell us that during cardiac arrest and
      CPR, forward flow of blood can be generated by external compression or
      decompression of either the chest or the abdomen. Standard CPR utilizes only one
      of these modes--chest compression--and generates roughly 1 L/min forward flow in
      an adult human, which is 20% of normal cardiac output. IAC-CPR uses two of these
      modes--chest compression and abdominal compression--and generates roughly twice
      the forward flow, or 2 L/min in an adult human. ACD-CPR uses two of these modes-
      chest compression and chest decompression--and also generates roughly twice the
      forward flow as standard CPR, although the results are somewhat model dependent.
      The studies by Sack et al with IAC-CPR and by Plaisance et al with ACD-CPR
      suggest that when methods that double perfusion are employed methodically,
      resuscitation outcome in terms of short- and long-term survival are also roughly
      doubled. This state of affairs is fortunate, because it is possible that factors,
      such as severe underlying disease or the quality of postresuscitation care, could
      blunt or cancel positive effects of improved blood flow during the brief
      resuscitation period. Theoretically, full four-phase CPR, including active
      compression and decompression of both chest and abdomen, is capable of generating
      4 L/min forward flow or greater, which is 80% of normal, and there is a
      reasonable prospect of achieving 100% of normal flow under conditions in which
      all four phases are optimized. Standard CPR is clearly not the ultimate form of
      external CPR. There is real, credible evidence that substantial improvements in
      resuscitation methods and results will be possible in the next decade.

PMID- 11845545
TI  - Pressor drugs in the treatment of cardiac arrest.
AB  - The importance of vital organ perfusion in patients suffering cardiac arrest
      makes arterial vasomotor tone, and the resultant perfusion pressure, critical in
      resuscitation from sudden death. Although there are multiple mechanisms that may
      affect arterial vascular tone, historically, the therapy most commonly used has
      been catecholamine-induced adrenergic receptor stimulation, with catecholamine
      epinephrine being the commonest drug used. Over the last decade, however, it has
      become widely known that the utility of epinephrine during cardiopulmonary
      resuscitation is undefined. This has led to research into alternative agents, in
      particular nonadrenergic vasoactive peptides. Other agents appear promising. This
      article addresses pressor drugs and adrenergic agonists, including a review of
      their history, basic science, mechanism of action, and efficacy. Epinephrine is
      reviewed.

PMID- 11845546
TI  - Advanced cardiac life support antiarrhythmic drugs.
AB  - As exemplified in this discussion of ACLS antiarrhythmic drugs, the evidence
      based evaluation process has created a high standard for the acceptance and
      ranking of therapies for cardiac arrest. This process also has identified
      critical areas needing further investigation, fostered a healthy sense of
      discomfort with the adequacy of our present interventions for cardiac arrest, and
      hopefully will continue to spur the science while sifting the dogma out of CPR.

PMID- 11845547
TI  - Postresuscitation myocardial dysfunction.
AB  - Postresuscitation myocardial dysfunction is common after prolonged cardiac arrest
      and can have life-threatening consequences. Experimental data suggest that
      systolic and diastolic left ventricular function can be adversely effected
      following successful resuscitation. Such dysfunction can resolve and represents
      true global myocardial stunning. Identified factors contributing to
      postresuscitation myocardial dysfunction include prolonged CPR, use of
      vasoconstricting drugs, and high-energy defibrillation. Potential treatments
      include dobutamine, KATP channel activators, and 21-aminosteroids. In the
      author's efforts to improve long-term survival from cardiac arrest, more
      attention is needed to the postresuscitation period.

PMID- 11845548
TI  - Meningitis concerns. Immunization recommended for group C type among children
      under five, teens and young adults.

PMID- 11845549
TI  - Toronto nurses charged. Criminal charges laid three years after girl's hospital
      death.

PMID- 11845550
TI  - A history of public health nursing in Alberta and British Columbia, 1918 to 1939.

PMID- 11845551
TI  - End of life. Assisted suicide. A challenge for today's nurses.

PMID- 11845552
TI  - Diabetes. Case management.

PMID- 11845553
TI  - Emergency lift for the immobile elderly.

PMID- 11845554
TI  - Making a case for home care.

PMID- 11845555
TI  - Anger, and plasma lipid, lipoprotein, and glucose levels in healthy women: the
      mediating role of physical fitness.
AB  - The association between anger, lipid profiles, and glucose levels were examined
      in this study of 103 middle aged, healthy women. A principal component factor
      analysis of Spielberger's Trait Anger and Anger Expression scales yielded two
      anger factors: Impulsive Anger-Out and Neurotic Anger. Impulsive anger-out
      significantly predicted a negative lipid profile (high total serum cholesterol
      (TSC), low density lipoproteins (LDL), TSC/HDL (high density lipids), and
      triglyceride levels) and heightened glucose levels, but only in physically unfit
      women. Neurotic anger did not predict lipid and glucose levels. These findings
      parallel previous findings regarding the two anger dimensions and CHD, with only
      impulsive anger-out predicting CHD. Furthermore, our findings indicate that the
      protective effect of physical fitness, previously documented for men, also occurs
      in women.

PMID- 11845556
TI  - Relation of diabetic patients' health-related control appraisals and physician
      patient interpersonal impacts to patients' metabolic control and satisfaction
      with treatment.
AB  - Desire for healthcare control, health locus of control, perceived control over
      diabetes, satisfaction with diabetes treatment, and general personality traits
      were assessed in 54 Type 1 and Type 2 diabetic patients of the same male
      endocrinologist during a regularly scheduled office visit. At the end of the
      consultation, both patients and the physician completed a measure describing the
      interpersonal impacts produced in each by the other's control and affiliation
      behaviors. Patient success at diabetes control was assessed via glycosylated
      hemoglobin A1C (HA1C) level on the day of the visit and variability in HA1C
      levels across several visits. Patients' satisfaction with treatment was unrelated
      to diabetes control measures. Patients' desire for behavioral involvement in
      their own healthcare and NEO Agreeableness scores were positively associated with
      diabetes control. Better diabetes control also resulted when the physician
      perceived patients to be more controlling and less submissive, and when there was
      more reciprocity in patient and physician's perceptions of the other's
      controlling interpersonal behavior. Findings support the conclusion that both a
      patient's self-reported desire for involvement in his or her healthcare and the
      transactional fit of patient-physician interpersonal behaviors are potentially
      important contributors to better diabetes outcomes.

PMID- 11845557
TI  - Predictive genetic testing: high risk expectations in the face of low risk
      information.
AB  - The aims of this cross-sectional, questionnaire study were (1) to estimate the
      proportion of those receiving negative ("low risk") results following predictive
      genetic testing who expect to undergo clinically unnecessary future screening and
      (2) to examine the factors associated with this expectation. Of 127 adults
      receiving negative results following predictive genetic testing for familial
      adenomatous polyposis (FAP), 54 people (42%) were expected to attend for future
      bowel screening. The main predictor was doubt about the accuracy of genetic test
      results. Expecting to attend was also associated univariately with perceiving the
      chance of developing FAP as higher, being more worried about this, perceiving the
      test result to be more uncertain and threatening, and holding a behavioral model
      of the cause of FAP. Attendance for health screening may be influenced by
      people's perception of the accuracy of genetic tests that they have undergone.
      Future research should investigate test presentation and influences on test
      perception.

PMID- 11845558
TI  - Heightened psychobiological reactivity to laboratory stressors in healthy women
      at familial risk for breast cancer.
AB  - This study examined the possibility that reactivity to acute stressors may be
      altered among women facing the chronic stress of being at familial risk for
      breast cancer. Sixteen healthy women with histories of breast cancer in their
      families (Risk Group) and 32 women at normal risk (Comparison Group) were exposed
      to 15 min of classic laboratory stressors. Seventeen women at normal risk were
      randomly assigned to nonstressful tasks (manipulation check). Self-reported
      distress, natural killer cell activity (NKCA), and NK cell numbers (percentage of
      CD3-CD16/56+ lymphocytes) were assessed before and after the tasks.
      Cardiovascular activity was assessed throughout the session. The tasks elicited
      increases in distress, heart rate, NKCA, and NK cells numbers in both
      experimental groups. Supporting study hypotheses, the Risk Group had larger
      increases in distress, heart rate, NKCA, and NK cell numbers. These findings
      raise the possibility that the chronic stress associated with familial cancer
      risk may have negative health consequences through changes in psychobiological
      reactivity.

PMID- 11845559
TI  - Risk involvement and risk perception among adolescents and young adults.
AB  - Adolescents as a group know about the connections between many risky behaviors
      and negative outcomes. However, it is unclear whether adolescents who engage in
      risky behavior differ in risk perceptions from those who do not. We proposed that
      risk differences between risk-involved and risk-uninvolved adolescents depend on
      how risk questions are framed. High school and college students estimated their
      risk of smoking and unprotected sex by replying to four different questions. The
      results revealed that, for both high school and college students, smokers saw
      their outcome risk (risk of negative outcomes) as higher than that of nonsmokers.
      A similar finding was obtained for sexual behavior, though only for high school
      students. No significant differences between risk groups were obtained when risk
      was measured by asking about behavior risk (general riskiness of the behavior).
      Overall, the data suggest that adolescents engaged in risky behavior do not have
      a complete appreciation of their exposure to harm. Programs intended to prevent
      or reduce risky behavior need to take a multifaceted approach to persuasion about
      risk.

PMID- 11845560
TI  - Initiation and maintenance of exercise behavior in older women: predictors from
      the social learning model.
AB  - The purpose of the present study was to determine the extent to which modifiable
      social learning constructs predicted long-term adherence to an exercise program
      in older individuals. Participants were 189 women aged 59 to 78 years and
      diagnosed with low bone density. Exercise behavior was assessed at 3-month
      intervals. Self-efficacy, readiness for change, orientation toward exercise,
      social support in general, and support specifically for exercise were measured at
      baseline and at 12-month follow-up. Analyses indicated that initial adoption of
      exercise behavior was best predicted by readiness to change. Maintenance was
      predicted by self-efficacy for exercise, and exercise behavior at 12 months was
      predicted by social support for exercise. The results were seen as supportive of
      the stages and processes of change model of health behavior change. Implications
      of the findings for interventions to enhance adoption and maintenance of exercise
      programs by older women are discussed.

PMID- 11845561
TI  - [Respiratory side-effects of drugs].
AB  - Three patients, men aged 65 and 49 and a woman of 38 years, presented with drug
      induced interstitial pneumonitis due to nilutamide, bleomycin and nitrofurantoin
      usage respectively. The signs and symptoms of drug-induced interstitial
      pneumonitis occur from within several hours up to months or years after the start
      of treatment, and sometimes even after the cessation of treatment, and consist of
      a dry cough, dyspnoea, fever and crackles upon auscultation. The results of
      further investigations are atypical and consist of abnormalities on the X-ray or
      CT of the thorax and lymphocytosis in the bronchoalveolar lavage fluid. The
      mechanisms of damage usually include direct pulmonary toxicity and indirect
      inflammatory or immunological processes. In most patients, the pulmonary
      abnormalities disappear after cessation of the drug treatment. Sometimes the
      disease progresses to pulmonary fibrosis and respiratory failure despite
      treatment with corticosteroids.

PMID- 11845562
TI  - [Revision needed of follow-up policy for Barrett's esophagus].
AB  - The frequency of adenocarcinomas at the oesophagocardial junction is increasing
      and, if symptomatic, the patients chances of cure are bleak. Given the
      association of Barrett's oesophagus (Barrett's oesophagus; denoting metaplasia of
      the oesophageal squamous cell lining to gastric-type mucosa) and oesophageal
      adenocarcinoma, it is plausible that establishing the presence of Barrett's
      oesophagus will subsequently enable two preventive strategies: primary, i.e. the
      treatment and eradication of Barrett's oesophagus, and secondary, the early
      diagnosis of (pre)malignancy during periodic endoscopic follow-up. Given the
      frequent occurrence of Barrett's oesophagus and the rarity of oesophageal
      adenocarcinoma there is a clear risk of overdiagnosis and overtreatment. Most
      studies on the effect of regular follow-up are uncontrolled and barely give any
      indication of a favourable outcome. Only a minority of patients with Barrett's
      oesophagus ought to have periodic endoscopic checkups: those with dysplasia or
      with one or more of the known risk factors (especially male gender, specialised
      type Barrett's oesophagus and long segment Barrett's oesophagus). Those patients
      must be healthy enough beforehand to undergo surgical treatment if necessary. The
      amount of quantity or quality of life that may be gained from this approach has
      yet to be established.

PMID- 11845563
TI  - [Once growth hormone, always growth hormone? Transition from growth hormone
      therapy in childhood to adulthood].
AB  - The continuation of growth hormone treatment can be indicated in young adults who
      have been treated with growth hormone during childhood. However, in a large part
      of this population the diagnosis cannot be confirmed in adulthood. Therefore a
      retest procedure has to be performed once the final height has been attained.
      This procedure is only unnecessary in patients with deficiencies of two or more
      other pituitary hormone axes. The retest procedure can be performed one to three
      months after the growth hormone treatment has been discontinued, by means of an
      insulin tolerance test or, in the case of contraindications, by means of a
      combined growth hormone-releasing hormone(GHRH)-arginine test. If the growth
      hormone deficiency diagnosis is re-established, growth hormone treatment can be
      restarted. Patients are only eligible for a reimbursement of the growth hormone
      treatment costs from their health insurer, if the treatment indication is
      validated by the Dutch National Registry of Growth Hormone Treatment in Adults
      and the treatment results are included in a database. With this database insights
      into the long-term efficacy and safety of growth hormone treatment can be gained.

PMID- 11845564
TI  - [Chronic simultaneous stimulation of both ventricles, a new treatment option for
      severe congestive heart failure].
AB  - Dilated congestive heart failure due to systolic left ventricle dysfunction
      frequently leads to intraventricular conduction disturbances with a prolonged QRS
      complex (> 120 ms). The prolonged conduction time in the ventricles causes
      electrical asynchrony of the ventricles and contributes to a further reduction of
      systolic function, changes of filling and relaxation intervals, and promotes
      mitral valve insufficiency. Chronic simultaneous stimulation of both the right
      and left ventricle in patients with severe heart failure improves functional
      status, quality of life, and exertion tolerance. At present the implantation of a
      biventricular pacemaker is time consuming because the positioning of the lead in
      a left ventricular epicardial vein is difficult. As congestive heart failure is
      frequently associated with an increased risk of ventricular fibrillation, the
      combined implantation of a biventricular stimulator and an implantable automatic
      defibrillator is sometimes necessary. Preliminary calculations show that about
      750 patients per year with severe congestive heart failure are eligible for a
      biventricular stimulator.

PMID- 11845565
TI  - [From gene to disease; hereditary multiple exostoses].
AB  - Hereditary multiple exostoses is an autosomal dominant disorder characterised by
      the presence of multiple osteochondromas, resulting in a variety of skeletal
      deformities. It is a genetically heterogeneous condition for which two genes,
      EXT1 and EXT2, have been isolated. The EXT1 gene, located at 8q24, has been shown
      to harbour mutations in 44-66% of the hereditary multiple exostoses-families.
      Mutations in the EXT2 gene, located at 11p11-p12, are detected in about 30% of
      the families. Additional linkage to chromosome 19p suggests the existence of an
      EXT3 gene. EXT1 has been shown to act as a tumour suppressor gene in hereditary
      multiple exostoses, resulting in osteochondroma formation when both copies of
      EXT1 are lost. Diagnostic germ-line mutation analysis is operative in the
      Clinical Genetic Center Leiden, the Netherlands.

PMID- 11845566
TI  - [Diagnostic image (73). A man with atypical back and abdominal symptoms.
      Inflammation of abdominal aortic aneurysm].
AB  - In a 66-year-old man a typical inflammatory abdominal aortic aneurysm was
      diagnosed.

PMID- 11845567
TI  - [Initiating insulin therapy in patients with diabetes mellitus type 2: in a
      transmural setting is at least as effective as in an outpatient setting; a
      retrospective study with a 4-year follow-up].
AB  - OBJECTIVE: Assessing whether the initiation of insulin therapy in patients with
      diabetes mellitus type 2 can be delivered as effectively in a structured
      transmural care model as in the more usual outpatients structure. DESIGN:
      Retrospective comparative cohort study. METHOD: In 1997 data were collected from
      52 patients with diabetes mellitus type 2 all of whom were above 40 years of age
      and transferred to insulin therapy in 1993: 25 in a transmural care setting and
      27 in an outpatients setting, both in Amsterdam, the Netherlands. Both groups
      were treated according to one protocol concerning the initiation and monitoring
      of insulin therapy, treatment goals and follow-up. Outcome measures were:
      percentage of glycated haemoglobin (HbA1c), health status, self-care behaviour
      and patient satisfaction. In 1993 the mean age was (transmural/outpatients
      setting): 67.5/65.3 years; percentage of men: 32%/48%; mean duration of diabetes:
      7.3/10.6 years; HbA1c: 9.1%/9.3%; mean body mass index: 27.4/29.1 kg/m2. RESULTS:
      In the period 1993-1997 the mean HbA1c decreased from 9.1% to 7.2% in the
      transmural care group and from 9.3% to 7.6% in the outpatients care group (both:
      p = 0.000). The percentage of patients with poor glycaemic control (HbA1c > 8%)
      decreased from 60 to 8 in the transmural care group and from 59 to 15 in the
      outpatients care group. The percentage of patients with good glycaemic control
      (HbA1c < 7%) increased from 4 to 52 in the transmural care group and from 11 to
      30 in the outpatients care group. No statistically significant differences were
      found between the patient groups with respect to health status, self-care
      behaviour and patient satisfaction. CONCLUSION: The transfer of patients with
      diabetes mellitus type 2 insulin therapy in a shared care setting was at least as
      effective as in an outpatients setting.

PMID- 11845568
TI  - [Bilateral pneumothorax in a young woman after acupuncture].
AB  - A 30-year-old woman presented at the emergency department with severe bilateral
      chest pain and shortness of breath. The complaints began after acupuncture
      treatment along the spine and paraspinal region of the thorax the previous day.
      Further examination revealed bilateral pneumothorax. Two days after insertion of
      chest drains, the patient was able to leave the hospital in a good condition.
      Bilateral pneumothorax after acupuncture of the thorax is a rare complication and
      its precise incidence is unknown. Acupuncturists as well as general practitioners
      and emergency room physicians should be aware that acupuncture of the thorax can
      lead to unilateral as well as bilateral pneumothorax.

PMID- 11845569
TI  - [Severe parkinsonism due to metoclopramide in a patient with polypharmacy].
AB  - A 73-year-old woman, with tuberculosis of the large intestine, developed nausea
      as a side effect of the antituberculosis drugs. The nausea was treated with
      metoclopramide. Subsequently she developed severe medication-induced
      parkinsonism. As her symptoms initially mimicked a depressive disorder, drug
      induced parkinsonism was only considered at a later stage. Due to drug-induced
      impaired function of the liver and kidney the patient had received a toxic dose
      of metoclopramide. Treatment with biperiden and withdrawal of the metoclopramide
      resulted in a reduction of the complaints within 3 months, after which the anti
      tuberculosis medication could be reintroduced. Adjusting the dose of
      metoclopramide could possibly have prevented this severe side effect.

PMID- 11845570
TI  - [Three patients with massive pulmonary embolism].

PMID- 11845571
TI  - [Follow-up after oncological surgery].

PMID- 11845572
TI  - [CBO guideline 'Oxygen therapy at home'].

PMID- 11845573
TI  - [Cognitive deterioration in the elderly due to primary hyperparathyroidism-
      resolved by parathyroidectomy].

PMID- 11845574
TI  - [Injury to the right A. pulmonalis due to blunt thoracic trauma].

PMID- 11845575
TI  - [The Medical School of Split--overview of its activity from independence until
      today].
AB  - The aim of this report is to describe the current status of medical education
      program in the University of Split Medical School and to investigate readiness to
      accept modern trends in medical education. The report comprises the four-year
      period, since establishment of independent medical school up to day. The crucial
      elements of the high education reform with special emphasis on medical education
      are included in the report. The development of the faculty is still burdened with
      lack of personnel, poor market orientation and relatively small scientific
      production. The financial report, scientific production data, and information
      about student performance are also included. The decision that all exams must be
      passed before enrolment to the next academic year showed full justification.
      Although exposed to strong criticism, our new curriculum implemented four year
      ago is still unchanged. Joint effort of all medical schools in Croatia has to be
      directed to the follow up of all information important for the medical education,
      development of the quality assurance mechanisms and to enhancing state
      examination, standard for the evaluation of the medical schools' quality.

PMID- 11845576
TI  - [Neisseria meningitidis with a decreased sensitivity to penicillin in the Zagreb
      District].
AB  - Of the total of 35 clinical isolates from blood and/or cerebrospinal fluid in
      patients from the Zagreb area in the period from 1996-1999 Neisseria meningitidis
      serogroup B was identified in 33 (94%). N. meningitidis strains with decreased
      susceptibility to penicillin have been occurring in Zagreb since 1998, and during
      the two-year period in this study we isolated 3/19 (16%) such strains (MIC, 0.12
      microgram/ml). Molecular typization of strains with decreased susceptibility to
      penicillin shows that they do not belong to a particular meningococcal clonal
      group. All isolated N. meningitidis strains were susceptible to the third
      generation cephalosphorins, quinolones and chloramphenicol. A single strain (3%)
      was resistant to rifampin, but 13/35 (37%) were resistant to
      trimethoprim/sulfamethoxazole. Consequently, trimethoprim/sulfamethoxazole is not
      recommended for chemoprophylaxis of meningococcal disease. Initially patients
      with meningococcal disease should be treated with the third generation
      cephalosporins, and further treatment should be continued in accordance with the
      antimicrobial susceptibility testing results. This study emphasizes the utility
      and importance of meningococcal disease monitoring throughout the Republic of
      Croatia.

PMID- 11845578
TI  - [Stenotrophomonas maltophilia as a cause of hospital infections--typing of
      clinical isolates using pulsed field gel electrophoresis] ].
AB  - Stenotrophomonas maltophilia (S. maltophilia) has been recognised now as an
      important cause of hospital infections. As S. maltophilia is resistant to many
      antibiotics, attempts have been made to identify the sources of S. maltophilia
      infection and route of its transmission. From July till October 1998, 22 isolates
      of S. maltophilia were obtained from 20 patients hospitalised at eight different
      wards. Strain typing was performed by macrorestriction analysis of chromosomal
      DNA by use of PFGE (XbaI and SpeI enzymes, in a CHEF DR III drive module). PFGE
      analysis of 22 S. maltophilia isolates revealed 9 different types designated by
      letters A to I. The source and route of the spread of infection could not be
      identified. These results may indicate that we had clusters of S. maltophilia
      infection in cardiosurgery ward and ICU by types A, B, C and D; in neurosurgical
      ICU by type E and in urology ICU by type H.

PMID- 11845577
TI  - [Respiratory allergy to house dust: Dermatophagoides pteronyssinus versus
      Dermatophagoides farinae] ].
AB  - House dust is one of the most common allergens that cause allergic respiratory
      diseases. It is a composed allergen, although the most important antigens are the
      mites Dermatophagoides pteronyssinus (Der p) and Dermatophagoides farinae (Der
      f). These mites have different geographic and climatic distribution. The aim of
      the study was to determine the sensitisation to Der p and Der f in our population
      of patients with respiratory allergic disorders. The investigation included 93
      patients with perennial rhinitis and/or asthma and positive skin reactions to
      dust mites. Concomitant sensitisation to Der f was found in 81% of the tested
      patients sensitised to Der p. The same size reactions to both mites was found in
      34% of patients. A larger diameter of the urtica to Der p was found in 39% of
      patients. In 10% a greater reaction was found to Der f than to Der p, while 3% of
      the subjects only had positive reaction to Der f. Patients with respiratory
      allergic diseases and skin sensitisation to dust mites in the investigated
      population were sensitised to Der p and Der f 97%:84%. In conclusion, most of our
      subjects were sensitised to both mites, although in some patients the correct
      diagnosis would not have been established if they had not been tested with Der p
      and Der f (in our investigation 19% of subjects). It is therefore suggested that
      both mites are used in the standard allergic skin prick test.

PMID- 11845579
TI  - [Reversible impairment of renal function during treatment with lisinopril, an ACE
      inhibitor (case report)].
AB  - ACE inhibitors are group of drugs whose use over the last ten years has largely
      expanded. New members of this group of drugs are developed and registered and
      today in Croatia exist a dozen ACE inhibitors from different pharmaceutical
      companies like lisinopril, cilazapril, ramipril, trandolapril, enalapril etc.
      Notable side effects of ACE inhibitors are: hypotension, dry cough, rash,
      angioneurotical edema, impaired renal function and acute renal failure. The aim
      of the article was to present a 72 year old patient with reversible impairment of
      renal function during treatment with ACE inhibitor lisinopril.

PMID- 11845580
TI  - [Metastasis of cutaneous squamous cell carcinoma of the face into the parotid
      area]].
AB  - Presence of planocellular skin carcinoma always implies the possibility of
      disease spreading into regional lymph nodes. The average occurrence of metastasis
      of this face carcinoma is about 5% (from 0.5% to 19.5%). This paper presents
      seven patients with lymphogenic metastasis of planocellular carcinoma of face
      skin into parotid region. All patients were treated surgically, and in three
      patients with extracapsular spreading of metastasis radiation therapy was
      applied. The choice of the extent of surgery was made on the basis of clinical
      status. In three patients with small solitary metastases superficial
      parotidectomy was performed as the only treatment method, and during the three
      year follow up the disease did not recur. in other four patients radical
      procedure with total parotidectomy and elective neck dissection was done due to
      greater number and size of parotid gland lymph nodes. During the second year of
      treatment of these patients, disease dissemination and lethal outcome were
      recorded. The importance of surgical treatment of the primary tumor is
      emphasized, as well as obligatory pathohistologic examination of the tissue
      (determination of the depth of invasion, edges), and frequent follow-up of
      patients at risk with the aim of early detection of recurrence and occult
      metastases.

PMID- 11845581
TI  - [Surgical treatment of irradiation-induced sarcoma after treatment for breast
      carcinoma, personal experience: 4 case reports] ].
AB  - In the Department of Plastic Surgery of "Dubrava" University Hospital from 1993
      to 1999 four patients were treated for radiation induced sarcoma. All of the
      patients were formerly operated for breast cancer and irradiated postoperatively.
      The mean time span between radiotherapy and development of sarcoma was 4.75
      years. Four patients were treated with wide excision and immediate reconstruction
      with local flaps. One of the patients had fibrosarcoma, two patients had
      lymphangiosarcoma, and one patient had osteosarcoma. Two patients died within two
      years. Radiation induced sarcomas are therapy resistant, and the review of
      literature did not show large controlled investigations which would offer the
      most optimal treatment. Most frequently a rapid progression of the disease is
      seen.

PMID- 11845582
TI  - [Continuous renal replacement therapy].
AB  - Acute renal failure (ARF) is a common clinical condition with significant
      mortality. Although intermittent hemodialysis (IHD) represents a standard method
      of renal replacement therapy in ARF, novel methods of continuous renal
      replacement therapy (CRRT) are becoming more important. CRRT allows an excellent
      control of uremia, volume and acid-base status, avoiding at the same time rapid
      fluctuations in effective plasma volume, plasma osmolality, or blood pressure.
      Methods of CRRT differ with respect to the predominant way of solute removal,
      utilizing convective clearance (continuous ultrafiltration and hemofiltration),
      diffusive clearance (continuous hemodialysis), or a combination of the both
      (continuous hemodiafiltration). Based on their properties, CRRT represent method
      of choice in the treatment of hemodynamically unstable patients with ARF.

PMID- 11845583
TI  - [The future of medical education and the Bologna process in Europe] ].

PMID- 11845584
TI  - [Medicine in sports or sport medicine?] ].
AB  - Sports medicine is a profession pertaining to primary health care of sport
      population (competitors, coaches, referees, participants in sports recreation).
      It embraces the physical and mental health protection and promotion of
      participants in relation to a particular sport activity and sport environment,
      directing athletes to a sport and adapting them to sport and the sport to them.
      Sports medicine takes part in selection procedure, training process planning and
      programming, and cares for epidemiological, hygienic, nutritional and other
      problems in sport. The Republic of Croatia belongs to those world states in which
      the field of sports medicine is regulated neither by a law or by profession. A
      consequence is that wide circle of physicians and paramedics work in clubs and
      various medical units without any legal or/and professional control not being
      adequately educated nor having licence for it. This review is an appeal to the
      Croatian Medical Chamber and the Ministry of Health to make efforts to promote
      the education and medical profession in sports medicine.

PMID- 11845585
TI  - [Gout in the past and uric arthritis today in Croatia] ].
AB  - In the past, gout was well known in these places, from Istria to Dubrovnik. Our
      very first dictionaries also witness about gout. Old doctors from Krapinske
      Toplice had also written about gout. Dr Edmund Mai, in his article published in
      "Lijecnicki vjesnik" in 1904 mentions "171 cases of uric arthritis". But, after
      that, for long 60 years there wasn't even a word about our patients, except
      surprise on very high incidence of the disease in the past. Even our handbooks
      had claimed that uric arthritis is not common in our country. In 1964 after 60
      years of silence, the first article about our patients with uric arthritis, was
      published in "Lijecnicki vjesnik". These patients were medically treated for
      average of 13 years, and still were misdiagnosed. After that article, the numbers
      of patients with gout and articles on uric arthritis permanently rise. Today, the
      incidence of gout in Croatia is similar to that in other European countries.

PMID- 11845586
TI  - [Dr. Ivo Sercer--a forgotten Croatian ophthalmologist] ].
AB  - Dr Ivo Sercer (Rakovac near Karlovac, 1892--Zagreb, 1959) graduated medical
      studies in Graz (1915) and specialized in ophthalmology. In April 1919 he was
      appointed head of the ophthalmology department of the City hospital in Subotica,
      where he worked until his death. Backa, a region spreading between the Danube and
      the Tisa, was one of Europe's major trachoma focal points and Subotica had an eye
      hospital ever since 1868. In that city a big City hospital with the medical,
      surgical and ophthalmological departments opened in 1897, and there Dr Sercer was
      very actively engaged. In addition to his hospital work Dr Sercer also ran a
      private practice, treated children in the Home for trachomatous children and
      worked as school clinic and health insurance ophthalmologist implementing the
      socio-medical programme for fighting trachoma devised by Dr Andrija Stampar.
      Regretfully, working outside the strict borders of his native country Dr Sercer
      has not received due recognition in the history of ophthalmology in Croatia.

PMID- 11845588
TI  - Youth and HIV/AIDS. Can we avoid catastrophe?

PMID- 11845587
TI  - [Antihypertensive agents after cerebral stroke are more effective than expected].

PMID- 11845590
TI  - A pathological service?

PMID- 11845589
TI  - A platform for genomics in South Africa.

PMID- 11845591
TI  - Harassment: what it is and what you can do about it.

PMID- 11845592
TI  - New-onset seizures in HIV-infected patients. A review and guide to management.

PMID- 11845593
TI  - Reconciliation in the UCT health sciences faculty--a vision for transformation.

PMID- 11845594
TI  - Medical art--a brief general overview, and its development in South Africa.

PMID- 11845595
TI  - And death shall be no more, comma, death thou shalt die.

PMID- 11845596
TI  - Violence against children in the Western Cape--a study by children for the
      benefit of children.

PMID- 11845597
TI  - Child rape--patterns of injury, management and outcome.

PMID- 11845598
TI  - High specificity makes DNA screening the method of choice for diagnosis of
      familial hypercholesterolaemia.

PMID- 11845599
TI  - Perceived and confirmed allergy in children with learning disabilities and
      hyperactivity.

PMID- 11845600
TI  - Invasive group A streptococcal infections after chicken pox--new in South Africa?

PMID- 11845601
TI  - Neuroendoscopy--report of initial experience.

PMID- 11845602
TI  - Social health insurance and tax-based funding of health.

PMID- 11845603
TI  - Clinical versus molecular diagnosis of heterozygous familial
      hypercholesterolaemia in the diverse South African population.
AB  - OBJECTIVE: Familial hypercholesterolaemia (FH) is a common genetic disease
      characterised by strikingly elevated plasma cholesterol concentration, which can
      lead to premature coronary death if left untreated. In this study DNA diagnosis
      of FH, which allows detection before onset of clinical symptoms, was evaluated
      against biochemical parameters routinely used to identify subjects with FH.
      DESIGN: A population-based strategy was used to identify low-density lipoprotein
      receptor (LDLR) gene defects in South Africans with clinical signs of FH,
      followed by a family-based DNA screening approach for presymptomatic diagnosis of
      FH. RESULTS: DNA screening of 790 at-risk relatives for the FH-related mutations
      identified in 379 index cases, allowed accurate disease diagnosis in an
      additional 338 relatives and exclusion of the relevant mutation in 452
      individuals. The sensitivity and specificity of the diagnosis, based on total
      cholesterol values measured in family members of FH heterozygous index cases with
      one of the three founder-related mutations, D154N, D206E and V408M, were 89.3%
      and 81.9%, respectively. CONCLUSION: The predominance of 10 LDLR gene mutations
      in the local population justifies population-directed DNA diagnosis of FH in
      South Africa on a routine basis, particularly since expression of the defective
      gene measured in biochemical tests does not allow accurate diagnosis of FH in all
      cases. DNA testing provides a definitive tool for family tracing aimed at pre
      clinical diagnosis and preventive treatment of FH.

PMID- 11845606
TI  - Expanded benefits for health devices system members. What's new in '02.

PMID- 11845604
TI  - Dihydropyridine calcium-channel blockers for antihypertensive treatment in older
      patients--evidence from the Systolic Hypertension in Europe Trial.
AB  - OBJECTIVE: The Syst-Eur study investigated whether active antihypertensive
      treatment could reduce cardiovascular complications in elderly patients with
      isolated systolic hypertension. DESIGN: Randomised, placebo-controlled, double
      blind outcome trial. SETTING: Hypertension clinics or general practitioners'
      surgeries in 198 centres in 23 Western and Eastern European countries. SUBJECTS:
      Patients aged > or = 60 years with sitting systolic blood pressure (BP) 160-219
      mmHg and sitting diastolic BP < 95 mmHg during run-in phase. METHODS AND RESULTS:
      Four thousand, six hundred and ninety-five patients were randomly assigned to
      active treatment (N = 2,398), i.e. nitrendipine, with the possible addition of
      enalapril and hydrochlorothiazide, or to matching placebos (N = 2,297). In the
      intention-to-treat analysis, the between-group difference in blood pressure (BP)
      amounted to 10.1/4.5 mmHg (P < 0.001). Active treatment reduced the incidence of
      fatal and non-fatal stroke (primary endpoint) by 42% (P = 0.003). On active
      treatment all cardiac endpoints decreased by 26% (P = 0.03) and all
      cardiovascular endpoints by 31% (P < 0.001). Cardiovascular mortality was
      slightly lower on active treatment (-27%, P = 0.07), but all-cause mortality was
      not influenced (-14%, P = 0.22). For total (P = 0.009) and cardiovascular
      mortality (P = 0.09), the benefit of antihypertensive treatment weakened with
      advancing age, and for total mortality it decreased with lower systolic BP at
      entry (P = 0.05). The benefits of active treatment were not independently related
      to sex or to the presence of cardiovascular complications at entry. The
      antihypertensive regimen was more effective in patients with diabetes than in
      those without diabetes at entry. Further analyses also suggested benefit in
      patients who were taking nitrendipine as the sole therapy. The per-protocol
      analysis largely confirmed the intention-to-treat results. Active treatment
      reduced all strokes by 44% (P = 0.004), all cardiac endpoints by 26% (P = 0.05)
      and all cardiovascular endpoints by 32% (P < 0.001). Total mortality was reduced
      by 26% (P = 0.05), but a similar reduction in cardiovascular mortality did not
      reach statistical significance in this analysis. Compared with placebo, active
      treatment also reduced the incidence of dementia by 50%. CONCLUSION: Stepwise
      antihypertensive drug treatment, starting with the dihydropiridine calcium
      channel blocker nitrendipine, improves prognosis in elderly patients with
      isolated systolic hypertension.

PMID- 11845605
TI  - Elim hospital--the first 100 years. Part 1.

PMID- 11845607
TI  - Hazard report. Reusable gaskets on oxygen regulators will wear out.

PMID- 11845608
TI  - Determining whether a device problem is unique.

PMID- 11845609
TI  - Picture archiving and communication systems.
AB  - Picture archiving and communication systems (PACS) are highly versatile data
      storage and retrieval systems that facilitate the transfer of digital images and
      patient data throughout a healthcare enterprise. Typically, they process images
      from diagnostic imaging modalities and are interfaced to radiology information
      systems (RISs) and hospital information systems (HISs) to help create a single
      patient record and improve overall workflow. For this Update Evaluation, we
      tested eight PACS from eight major suppliers. Ideally, a PACS should allow the
      facility to achieve a fully automated workflow, in which patient data could move
      seamlessly from one system to another in a single electronic medical record.
      Although our testing found that this ideal has not yet been realized, many of the
      evaluated systems have taken significant steps in that direction. Three of the
      systems covered in this issue were originally tested for our November 2000
      Evaluation. Because PACS technology evolves so rapidly, we haven't simply
      provided updated data on these three systems, as we customarily would for an
      Update Evaluation. Instead, we have reexamined the systems from top to bottom and
      are presenting the results in brand-new Product Profiles, alongside the profiles
      for the five other systems evaluated here for the first time.

PMID- 11845610
TI  - Diversion: where are you going? Overload of patients forcing Georgia hospitals
      into diversion.

PMID- 11845611
TI  - Proposed rules outline debarment of providers from participation in the Federal
      Employees Health Benefits Program.

PMID- 11845612
TI  - [What is your diagnosis? Sensory motor polyneuropathy in borderline leprosy.
      Trophic skin disorders with ulcerations, local superinfection on the right foot
      with right inguinal lymphadenopathy].

PMID- 11845613
TI  - [Reduction of severe hypoglycemia by functional insulin therapy of type I
      diabetes mellitus].
AB  - Life style has to be adapted to insulin regimens in conventionally intensified
      insulin therapy. Functional insulin therapy (FIT) allows for flexible adjustments
      to changing insulin requirements. FIT is based on separating the substitution of
      basal, meal dependent and correction insulin by the patient. The patient has to
      acquire special knowledge. We here report longitudinal data of 183 patients out
      of 221 patients who have been educated by FIT outpatient programs in the years
      1990 to 1996. The 3 month FIT education program consisted of sixteen hours in
      total. Five and a half hours were held in a whole day preparation seminar and the
      other seven hours in evening sessions each of 90 minutes duration. Prior to FIT
      education patients were treated by intensified conventional insulin therapy. Mean
      glycosylated hemoglobin prior to FIT education was 7.0% (normal range 3.7-5.6%).
      After FIT education glycosylated hemoglobin remained unchanged. However, the
      percentage of patients experiencing severe hypoglycemic episodes (stupor and
      coma) in a one year course was significantly reduced from 26% prior to FIT
      education to 14% after FIT education--hypoglycemic coma was reduced from 13% to
      7% respectively. Thus, we can report that FIT reduces the risk of severe
      hypoglycemia. We believe that our data should stimulate the broad supply of FIT
      education programs available to diabetes patients in Switzerland.

PMID- 11845614
TI  - [Mansonella perstans filariasis after stay in Cameroon. A 19-year-old patient
      born in Cameroon, in Switzerland for the last 10 years].
AB  - After a spending three weeks in Cameroon, a 19-year-old woman presented in the
      emergency room with sudden lancinating pain in the lower abdomen, predominantly
      on the right side. A blood smear tested for presumed malaria showed subperiodic
      microfilariae of the species Mansonella perstans. The patient was treated with
      mebendazole (Vermox).

PMID- 11845615
TI  - [Value of laboratory diagnosis in inflammatory rheumatologic diseases].
AB  - Laboratory investigations play an important part in the diagnostic procedures of
      inflammatory rheumatic diseases. Besides the classical humoral inflammatory
      parameters (erythrocyte sedimentation rate, C-reactive protein, protein
      electrophoresis), hematology, blood chemistry, infectious serology and synovial
      fluid analysis we want to focus in this review on the more detailed diagnostic by
      autoantibody testing as well as by specific molecularbiological procedures (PCR
      technique).

PMID- 11845617
TI  - [Scleral icterus in a 22-year-old housewife].

PMID- 11845616
TI  - [Age-related macular degeneration].

PMID- 11845618
TI  - Knowledge in nursing: contemplating life experience.
AB  - Nurses' life experiences result in a subjective way of knowing an event, a way of
      knowing that is embedded in beliefs, values, traditions, religious and cultural
      observances, and other contextual layers of life. Thus, in order to more fully
      understand nursing knowledge, we must illuminate knowledge that comes from life
      experience and examine how the context of nurses' lives, and practice, delimits
      its expression. Few authors have made explicit reference to nurses' lives outside
      clinical practice, or have sought to understand how life experiences contribute
      to the way in which they know nursing. This article describes life-informed
      knowledge, what it is and why it needs to be considered to further our
      understanding of nursing knowledge.

PMID- 11845619
TI  - Women and heart disease: the treatment may end but the suffering continues.
AB  - Though heart disease is the number one health problem among women, men continue
      to represent the majority of those in cardiac rehabilitation for secondary
      prevention. Research has shown that conventional rehabilitation programs do not
      meet the needs of women recovering from cardiac events. Women's primary
      rehabilitative need may be support, particularly from women with similar
      experiences. Furthermore, the need for support in living with heart disease may
      persist beyond the in-hospital phase of recovery. The purpose of this study was
      to develop and implement a community-based communication and psycho-educational
      support group for women with heart disease. Participatory action research was the
      methodology selected. Two groups of women (n = 16) met monthly for 5 months to
      develop the program. Sessions were facilitated jointly by a nurse clinician and a
      nurse-researcher. Between sessions, participants kept diaries of their
      experiences. Data consisted of videotapes and transcriptions of the sessions,
      field notes, and the women's diaries and final evaluation. Initial analysis
      revealed that the value of the group for the women was threefold: it helped them
      to cope with their emotional reactions, offered social support, and helped them
      to manage their health problem. Iterative analysis unveiled a meta-paradigm
      consistent with the concept of suffering. The apparent overall benefit of a
      community-based psycho-educational support group for women with heart disease is
      acknowledgement and sharing of suffering, something that cannot readily occur in
      women's other life arenas.

PMID- 11845620
TI  - Women's health.

PMID- 11845621
TI  - Impressions of breastfeeding information and support among first-time mothers
      within a multiethnic community.
AB  - The purpose of this study was to document mothers' perceptions of breastfeeding
      information and support received from hospital- and community-based health
      professionals within a multiethnic community. A telephone survey was conducted to
      assess: mothers' impressions of professional support for breastfeeding, whether
      recommended breastfeeding practices were followed by health professionals, and
      the nature and sources of breastfeeding information received. An ethnically
      diverse sample of 108 first-time breastfeeding mothers was surveyed at 3 weeks
      postpartum. Overall, the mothers' evaluations of professional support for
      breastfeeding were positive, even though they reported breastfeeding practices
      that fell short of recommended standards. Immigrant mothers were found more
      likely to experience hospital practices detrimental to breastfeeding success than
      Canadian-born mothers, but were also found more likely to receive professional
      breastfeeding support in the community. Significant differences were also found
      between immigrant and Canadian-born mothers in the sources of their breastfeeding
      information. The findings underscore the key role of nurses in ensuring the
      promotion and optimal support of breastfeeding.

PMID- 11845622
TI  - The intersection of relational and cultural narratives: women's abortion
      experiences.
AB  - Although a great deal has been written on women's personal deliberations in
      deciding to have and seeking an abortion, little has been written on the
      experience of living with this decision or on the meanings an abortion generates
      in the context of a particular life. In this hermeneutic phenomenological study,
      14 women aged 19-44 expressed a need for professionals and others to accept the
      reality of unplanned pregnancy and to acknowledge that the choice of abortion
      cannot be fully understood in isolation from women's other reproductive choices.
      Using a feminist analysis of the tensions and contradictions in the women's
      accounts, the authors explore the intersections between their experiences and the
      cultural narratives in which they are situated, in a search for new possibilities
      for women and new understandings of women's experience of abortion.

PMID- 11845623
TI  - Research priorities in gender and health.

PMID- 11845624
TI  - Ren and Yuan: a cultural interpretation of Chinese women's responses to
      battering.
AB  - The purpose of the study was to examine women's responses to battering within the
      context of Chinese culture. The stories of 11 Chinese women living in Hong Kong
      formed the basis of the inquiry. Analysis of the women's accounts revealed
      Chinese values in their responses to battering: they adopted ren, or endurance,
      as a coping mechanism and used Yuan, or predestination, as an explanation for
      their failed relationship. The resilience and resourcefulness of the women are
      clearly demonstrated in the strategies they employed to cope with the abuse.
      Their responses to battering were purposeful and varied according to the status
      of their relationship.

PMID- 11845625
TI  - Conducting health research with vulnerable women: issues and strategies.
AB  - This paper has summarized a variety of methodological and ethical issues in
      conducting research with vulnerable women, and has also proposed strategies for
      dealing with these issues. Because vulnerable women are at increased risk for
      health problems, it is imperative that nurses and other health-care professionals
      make strenuous efforts to include vulnerable women in health research.

PMID- 11845626
TI  - Sticks and stones: racism as experienced by adolescents in New Brunswick.
AB  - The purpose of the study was to describe both the nature of racism as experienced
      by adolescent self-described victims in the province of New Brunswick and their
      response to the perceived racist incidents. A qualitative methodology based on
      the constructivist paradigm was used. In-depth interviews were conducted with non
      White adolescent victims of racism and with parents of victims. Although the
      study was initiated in response to an eruption of publicity about teenage racial
      violence, the findings indicate that racist incidents were not a new phenomenon
      for the participants. They described a low-key but long-term problem that had
      begun when they entered the public school system. Name-calling was by far the
      most common form of racism identified and it played a part in most of the other
      incidents described; dismissed as harmless by authority figures, it appeared to
      have long-term consequences for its targets. The participants' response to racism
      was found to have three phases: splintered universe, spiralling resistance, and
      disengagement. The results suggest that nurses working in the field of school
      health should address issues of racism among children and adolescents.

PMID- 11845627
TI  - A difficult diagnosis of a child's sore throat.

PMID- 11845628
TI  - The scrub sink.

PMID- 11845629
TI  - Meeting the health needs of refugees and immigrants.

PMID- 11845630
TI  - Resource use by physician assistant services versus teaching services.
AB  - OBJECTIVE: To compare resource use in physician assistant (PA) services versus
      teaching services for 5 medical diagnostic groups in a large community teaching
      hospital, while controlling for attending physician. METHODS: The sample was
      drawn from an administrative database of patients admitted to an internal
      medicine service in which attending physicians' cases rotated between the PA and
      teaching services on a preassigned schedule. Diagnoses included in the study were
      stroke (diagnosis-related group [DRG] 014), pneumonia (DRG 089), acute myocardial
      infarction (DRG 122), congestive heart failure (DRG 127), and gastrointestinal
      hemorrhage (DRG 174). Cases discharged between January 1, 1994, and June 30,
      1995, were evaluated. Inclusion of cases was based on the Integrated Inpatient
      Management Model (IIMM). Resource use was measured using direct costs expressed
      as relative value units (RVUs) for radiology, laboratory, and total resource use,
      as well as for length of stay (LOS). RESULTS: After adjustment for admitting
      physician effects and other covariates, the mixed model analyses indicated that
      PAs used fewer total ancillary resources for patients with pneumonia and fewer
      laboratory resources for patients with stroke, pneumonia, and congestive heart
      failure than did residents, on average. No significant differences were noted in
      average LOS or use of radiology resources between PA and teaching services. In no
      cases did PAs use significantly more resources than residents. However,
      significantly higher mortality among pneumonia cases was detected for PAs.
      CONCLUSIONS: In the same practice setting, PAs used resources as effectively as,
      or more effectively than, residents.

PMID- 11845632
TI  - Corneal abrasion: should you patch the eye?

PMID- 11845631
TI  - Understanding the problem of urinary incontinence.

PMID- 11845633
TI  - Coming to terms with direct-to-consumer advertising.

PMID- 11845634
TI  - Legislative issues impacting on the practice of the South African nurse
      practitioner.
AB  - PURPOSE: To present an overview of the impact of the nurse practitioner (NP) on
      the South African health care arena and describe the legislative framework for NP
      practice. DATA SOURCES: Statutes and laws of the government of South Africa;
      published professional guidelines; authors' experiences. CONCLUSIONS: The key
      challenges for NPs in South Africa lie in lobbying for enabling legislation,
      obtaining access to education and training opportunities, and managing risks
      within the rapidly changing environment. IMPLICATIONS FOR PRACTICE: Some aspects
      of the NP's accountability and responsibilities have as yet not been adequately
      addressed in the current legislative framework and will certainly increase the
      risk for malpractice. South African NPs will have to establish partnerships with
      important role players, not only in South Africa, but also internationally, to
      ensure that an enabling environment for quality health services is created.

PMID- 11845635
TI  - Clinical practice guidelines. Managing oral anticoagulant therapy.
AB  - Clinical practice guidelines (CPG) provide recommendations based on the summary
      of large volumes of literature and expert opinion. They are not absolute care
      directives, but are intended to facilitate individualized decision making related
      to patient care situations. Each month this column reviews a CPG of direct
      relevance to clinical practice. Readers are urged to contact the author, Mary Jo
      Goolsby (mjgoolsby@aanp.org) with requests for reviews of specific clinical
      guidelines or submissions of manuscripts addressing major guidelines that readers
      have found helpful in their practice. The Clinical Practice Guideline column is
      designed to inform practitioners of the wide range of accessible and current
      recommendations on a myriad of clinical topics. The guideline reviewed this month
      is actually one part of a large report stemming from the Sixth American College
      of Chest Physicians (ACCP) Consensus Conference on Antithrombotic Therapy. The
      management of oral anticoagulant therapy is but one portion of the overall
      report, complemented and supported by other components, including a preceding
      chapter that summarizes the mechanisms of action, clinical effectiveness, and
      therapeutic range of oral agents. This CPG focuses on following issues: (a)
      initiating and maintaining dosage, (b) managing non-therapeutic dosages, (c)
      managing the agents during invasive procedures, and (d) recognizing and
      responding to adverse events. Special situations are discussed, including
      management of patients who are elderly or pregnant, and comparisons of the
      management in different models of care. There is in-depth discussion of the
      literature, accompanied by a summary of recommendations.

PMID- 11845636
TI  - Mutual timing: an essential component of provider/patient communication.
AB  - PURPOSE: To present a concept clarification in an effort to give a name to a
      commonly experienced but poorly understood communication process: mutual timing.
      DATA SOURCES: Extensive literature review of scientific and nursing literature;
      relevant theories; standardized process for concept clarification as delineated
      in the literature. CONCLUSIONS: Good communication involves many familiar
      concepts, including good eye contact, attentive listening and the use of silence
      and touch. Mutual timing is the difference-making moment, creating common ground
      in the midst of engagement. Concept clarification is a critical step to
      understanding important practice concepts. Wedding the concept to everyday
      practice provides the beginning for development of guidelines, which can be used
      by nurse practitioners (NPs) for making decisions while caring for patients.
      IMPLICATIONS FOR PRACTICE: Nursing has claimed to be privy to a special
      relationship with patients that differs from other health care professions. When
      asked to differentiate their care from that of physicians, NPs are often quoted
      as valuing the psychosocial aspect of care and stressing the importance of their
      relationship with patients. Many NPs define themselves in terms of relationship,
      emphasizing strong moral obligations and mutual commitments with their patients.
      One of the core processes of the effective patient/provider relationship is good
      communication.

PMID- 11845637
TI  - The female athlete triad: a terrible trio implications for primary care.
AB  - PURPOSE: To describe the components of the female athlete triad, including
      definitions and clinical criteria for diagnosis, methods of screening, and
      treatment options. DATA SOURCES: Selected scientific literature; standard
      diagnostic guidelines. CONCLUSIONS: The female athlete triad is a cascading event
      consisting of disordered eating, amenorrhea, and osteoporosis. This disorder can
      occur in any sport but is seen most often in events that emphasize thinness and
      appearance such as gymnastics, ballet, and diving. It can often go unrecognized
      and result in irreversible bone loss and possible death. IMPLICATIONS FOR
      PRACTICE: Primary care nurse practitioners (NPs) may be the first health care
      professionals encountering these females; they need to recognize the risk factors
      and institute a multidisciplinary approach to treatment. The treatment team
      should be composed of the patient, the NP, a dietitian, a psychologist,
      psychiatrist, or psychiatric nurse specialist, and the patient's family, coaches,
      and trainers.

PMID- 11845638
TI  - Developing an economic IQ in primary care.
AB  - PURPOSE: To describe elements of an economic intelligence quotient (IQ) that can
      be used to enhance the nurse practitioner's (NP) fiscal viability in a primary
      care setting. DATA SOURCES: Anecdotal data from providers and administrators;
      clinical experiences of the authors; scientific and government publications and
      guidelines. CONCLUSIONS: In the United States, managed care cost-containment
      initiatives have led to competition among physicians and NPs for patients and
      jobs. An understanding of the economic base of a practice is essential to fiscal
      viability in this market. PRACTICE IMPLICATIONS: When turf and job competition
      are the norm, it is essential that the NP develop an economic IQ. Knowledge of
      coding, billing, reimbursement, and documentation are critical to identifying the
      NP's value to the practice and promoting job retention. The challenge is for the
      NP to give high-quality, cost-effective, and safe patient care and to be a
      productive provider.

PMID- 11845639
TI  - Secondary hypertension in a migrant farm worker: a case report of coarctation of
      the aorta.
AB  - PURPOSE: To report a case of undetected aortic coarctation in an adult Hispanic
      migrant farm worker that presented with uncontrolled hypertension and transient
      left flank pain. A primary care overview of the disorder, clinical diagnosis,
      testing, and treatment are discussed. DATA SOURCES: Case report, scientific
      literature, diagnostic evidence. CONCLUSIONS: Coarctation of the aorta is a
      significant congenital cardiovascular anomaly and cause of secondary
      hypertension. The majority of patients with coarctation of the aorta are
      diagnosed during infancy. Older children and adults may have a subtle
      presentation, but can be identified as being at risk by having a thorough history
      and physical, as well as noninvasive diagnostic testing. IMPLICATIONS FOR
      PRACTICE: Primary care providers must have a high degree of suspicion in patients
      with risk factors or in individuals that may have not benefited from adequate
      health screening. Early diagnosis and correction of the coarctation is important
      to reduce persistent postoperative hypertension and improve long-term survival.

PMID- 11845640
TI  - Literacy in the health care system: a study on open heart surgery patients.
AB  - PURPOSE: To determine if patients recovering from open heart surgery were able to
      read and understand written discharge instructions and further to analyze the
      level of difficulty of standard discharge instructions and consent forms for open
      heart surgery. DATA SOURCES: After screening for visual acuity and efficiency,
      literacy was assessed with the Rapid Estimate of Adult Literacy in Medicine test
      (REALM) and comprehension was tested by a post-test of five questions based on
      the discharge instructions. Flesch-Kincaid scores were calculated on four sets of
      standard written discharge instructions and consent forms. CONCLUSIONS: Results
      from the study indicated that the REALM test was more accurate than the reported
      grade level and that reading skills are needed to understand and comprehend
      information needed for post-operative care. The study further substantiated that
      health care facilities are not providing written instructional material that is
      within the reading level of the patient. IMPLICATIONS FOR PRACTICE: Illiteracy
      can have a major impact in the health care system. Low reading skills can
      disempower and can prove to be costly for patients who are requiring health care
      services. Further investigation is needed on the impact of patients' reading
      skills on the health care system.

PMID- 11845641
TI  - Primary care cancer and diabetes complications screening of black women with type
      2 diabetes.
AB  - PURPOSE: To determine the frequency with which Black women with type 2 diabetes
      receive routine primary health care screening for cancer and diabetes
      complications. DATA SOURCES: Pilot study data from a convenience sample of 21
      Black women (mean age 46.8 years) with type 2 diabetes. CONCLUSIONS: Cancer
      screening consisted of Pap smear, mammography, and colon cancer screening
      consistent with current American Cancer Society recommendations. Ninety percent
      reported having had a Pap smear, 86% mammogram and 33% colon cancer screening.
      Diabetes complications screening was based on the American Diabetes Association
      care recommendations. Fifty-five percent received screening eye exams, 40% were
      screened for renal proteinuria, and 50% received foot examinations and diabetes
      foot care instruction. IMPLICATIONS FOR PRACTICE: This sample of mid-life, Black,
      educated, working women with type 2 diabetes utilize healthcare services and have
      high rates of primary care cancer screening. Rates of diabetes complications
      screening are less than optimal. Because Black American women suffer
      disproportionately high rates of diabetes and related complications, it is
      imperative that they receive quality diabetes care in an effort to improve health
      outcomes and decrease premature mortality.

PMID- 11845642
TI  - Consequences of divorce on the adjustment of children in China.
AB  - Explored the consequences of divorce on children in China. In contrast to Western
      countries, divorce in China is relatively rare, occurring in approximately 10% to
      15% of the population. Children from divorced families (n = 174) and matched
      intact families (n = 174) were selected from a larger sample of 1,294 children
      between 8 and 14 years of age. Divorce was relatively low in this sample (13.45%)
      of participants, consistent with rates observed in epidemiological studies in
      China. Mothers of divorced children reported higher levels of education but lower
      levels of income than mothers in intact families. Children in divorced families
      reported higher levels of anxiety and depression, and their mothers and teachers
      rated them as possessing more behavior problems on the Achenbach (1991) Child
      Behavior Checklist scales. Regression analyses revealed that rejecting and
      inattentive parenting styles, along with family status (divorce or intact), high
      maternal depression, and sex (boys) predicted significant amounts of variance
      associated with these negative outcomes. Results are discussed in terms of
      familial and cultural issues associated with these findings.

PMID- 11845643
TI  - The development and psychometric properties of a measure of social and adaptive
      functioning for children and adolescents.
AB  - Developed, piloted, and examined the psychometric properties of the Child and
      Adolescent Social and Adaptive Functioning Scale (CASAFS), a self-report measure
      designed to examine the social functioning of young people in the areas of school
      performance, peer relationships, family relationships, and home duties/self-care.
      The findings of confirmatory and exploratory factor analysis support a 4-factor
      solution consistent with the hypothesized domains. Fit indexes suggested that the
      4-correlated factor model represented a satisfactory solution for the data, with
      the covariation between factors being satisfactorily explained by a single,
      higher order factor reflecting social and adaptive functioning in general. The
      internal consistency and 12-month test-retest reliability of the total scale was
      acceptable. A significant, negative correlation was found between the CASAFS and
      a measure of depressive symptoms, showing that high levels of social functioning
      are associated with low levels of depression. Significant differences in CASAFS
      total and subscale scores were found between clinically depressed adolescents and
      a matched sample of nonclinical controls. Adolescents who reported elevated but
      subclinical levels of depression also reported lower levels of social functioning
      in comparison to nonclinical controls.

PMID- 11845644
TI  - Sluggish cognitive tempo predicts a different pattern of impairment in the
      attention deficit hyperactivity disorder, predominantly inattentive type.
AB  - Compared 2 groups of children with attention deficit hyperactivity disorder,
      predominantly inattentive type (ADHD/IA)--those with high scores on a composite
      measure of sluggish cognitive tempo (SCT) and those without--using a large,
      school-based sample of children for which previous comparisons between ADHD
      subtypes have been reported. Although the 2 groups did not differ on level of
      attention or learning problems, high-SCT ADHD/IA children were rated by teachers
      as showing less externalizing behavior and higher levels of unhappiness,
      anxiety/depression, withdrawn behavior, and social dysfunction. Thus, SCT
      identifies a more homogeneous subgroup of ADHD/IA children who are, relative to
      the entire Diagnostic and Statistical Manual of Mental Disorders (4th ed. [DSM
      IV]; American Psychiatric Association [APA], 1994) diagnosed ADHD/IA group, more
      similar to those classified in previous research as "attention deficit disorder
      without hyperactivity." These results support a reconsideration of SCT symptoms
      as a component of diagnostic criteria for a category of nonhyperactive attention
      deficit disorder.

PMID- 11845645
TI  - Analysis of variance frameworks in clinical child and adolescent psychology:
      issues and recommendations.
AB  - Reviewed existing practices of factorial analysis of variance (ANOVA), a major
      analytic tool used in clinical child and adolescent psychology, in the Journal of
      Clinical Child Psychology (JCCP) and noted several suboptimal strategies. Issues
      surrounding the analysis of multiple outcome variables, omnibus F tests, and
      single degree of freedom contrasts, simple main effects analysis, and single
      degree of freedom interaction contrasts were considered and recommendations were
      made about analytic strategies. Among the practices questioned were the use of
      multivariate analyses of variance (MANOVAs) as a means of controlling Type I
      errors across multiple outcome variables and the use of simple main effects
      analysis to elucidate the nature of interaction effects.

PMID- 11845646
TI  - Behavior problems among preschool children born to adolescent mothers: effects of
      maternal depression and perceptions of partner relationships.
AB  - Investigated how maternal depression influenced the relation between mothers'
      perceptions of the quality of their partner interactions and behavior problems
      among their preschool children. Participants included 194 low-income families
      from 4 sites. Approximately three fourths of the mothers (72%, n = 139)
      identified a male partner and comprised the analysis sample. Mothers were
      adolescents (< or = age 19) at delivery, and data were gathered when children
      were 4 to 5 years of age. In this high-risk sample, 42.4% of the children had
      been maltreated, 36% had externalizing scores in the clinical range, and 10.8%
      had internalizing scores in the clinical range. Multiple regression analyses
      revealed (a) maternal perceptions of negative partner interactions were
      associated with more internalizing behavior problems among the children,
      adjusting for the effects of maltreatment; (b) maternal depression mediated the
      relation between the maternal perceptions of the quality of partner interactions
      and children's internalizing and externalizing behavior problems; and (c)
      maternal perceptions of positive partner interactions did not protect children
      from internalizing or externalizing behavior problems associated with
      maltreatment. Programs for adolescent mothers should provide screening and
      treatment for depressive symptoms and help partners negotiate caregiving roles
      and mutually satisfying relationships.

PMID- 11845647
TI  - Sex-specific predictors of suicidality among runaway youth.
AB  - Examined predictors of suicidality (ideation and attempts) among 348 adolescent
      runways (197 boys; 56% African American; M age = 16) using sex-specific models
      that tested the impact of the three domains of the Social Action Model:
      individual characteristics, interpersonal influences, and life events. Twenty
      five percent of the girls and 14% of the boys had attempted suicide at least
      once. Male suicidality was mainly predicted by individual characteristics:
      identifying as gay, emotional distress, fewer conduct problems, and avoidant
      reasons for drug use. The interpersonal influence of suicidal friends also
      predicted suicidality. Variables from all three domains influenced girls:
      individual characteristics of lower age, lower self-esteem, and emotional
      distress; interpersonal influence of suicidal friends; and life events of having
      lived on the streets and assaults. Findings suggest some sex-specific
      interventions, but decreasing emotional distress and lessening the influence of
      suicidal friends may be useful for both boys and girls.

PMID- 11845648
TI  - Growing a journal up, growing up the field.

PMID- 11845649
TI  - Treatment-as-usual for adolescent suicide attempters: implications for the choice
      of comparison groups in psychotherapy research.
AB  - Studied Treatment-as-Usual (TAU) in a sample of 63 adolescent suicide attempters.
      Randomized clinical trials (RCT's) with high-risk populations, such as suicidal
      patients, are difficult to conduct due to clinical and ethical concerns about
      control groups. Therefore, TAU comparison groups have been proposed as ethically
      defensible alternatives to control groups. However, TAU is rarely characterized
      in treatment trials. Following a suicide attempt, the adolescents in our sample
      reported attending 0 to 22 outpatient psychotherapy sessions, with an average of
      7.0 sessions. Fifty-two percent of the adolescents reported attending six or
      fewer sessions. Supportive psychotherapy techniques were reported by three
      fourths of the sample, psychodynamic and cognitive techniques by one half of the
      sample, and behavioral techniques by one third of the sample. Results suggest
      that TAU with this population of adolescents is highly variable, both in terms of
      the number of sessions attended and type of treatment received. This variability
      makes interpretation of treatment results in clinical trials with TAU comparison
      groups tenuous. Given the attention paid to treatment attendance and fidelity in
      most RCTs, even less potent control groups in such trials may be both ethically
      and clinically as justifiable as TAU designs for high-risk populations.

PMID- 11845650
TI  - Examination of affective, cognitive, and behavioral factors and suicide-related
      outcomes in children and young adolescents.
AB  - Examined the role of affective, cognitive, and behavioral factors in the
      occurrence of suicidal ideation, suicide attempts, and suicidal intent in child
      and young adolescent (N = 175, ages 6 to 13 years) psychiatric inpatients. The
      results indicated that (a) self-reported depressed mood, negative automatic
      thoughts, hopelessness about the future, and anhedonia were all significantly
      associated with suicide-related outcomes, and these relations remained
      statistically significant even after depressed mood was controlled; (b) suicidal
      participants (both ideators and attempters) were distinguished from nonsuicidal
      participants by higher scores on measures of depressed mood, negative automatic
      thoughts, and hopelessness; and (c) participants who reported making a suicide
      attempt were distinguished from those who did not by higher scores on a measure
      of anhedonia and a higher number of previous suicide attempts. The results
      demonstrate the importance of negative automatic thoughts and anhedonia, and
      provide support for the role of hopelessness and previous suicide attempts in the
      occurrence of different suicide-related outcomes in children and young
      adolescents.

PMID- 11845651
TI  - Peer victimization, global self-worth, and anxiety in middle school children.
AB  - Examined relations among peer victimization, global self-worth, and anxiety, with
      particular interest in the potential mediating and moderating effects of global
      self-worth in the anticipated relations between peer victimization and anxiety.
      Sixth-grade children (N = 279) from a public middle school in southwestern
      Virginia participated. Reported levels of peer victimization were similar to
      those reported in previous studies, as were levels of anxiety. Sex differences
      were noted on measures of peer victimization and anxiety with boys reporting more
      victimization but less anxiety than girls. All subsequent analyses were conducted
      separately by sex. Significant relations were found among all variables of
      interest. For girls, global self-worth was found to mediate the peer
      victimization-anxiety relation, suggesting that victimization experiences
      negatively influenced girls' views of themselves and helped explain elevated
      levels of anxiety reported by them. For boys, global self-worth moderated the
      peer victimization-anxiety relation. Boys with higher global self-worth reported
      fewer anxiety symptoms than boys with lower global self-worth. Implications of
      these findings are discussed.

PMID- 11845652
TI  - Coordination of maternal directives with preschoolers' behavior: influence of
      maternal coordination training on dyadic activity and child compliance.
AB  - Investigated the impact of a specific intervention on child cooperation. The
      intervention was designed to increase maternal coordination with child behavior.
      Mothers assigned to the experimental condition were instructed on how to modulate
      the specificity of directives to their preschooler as a function of the child's
      moment-to-moment behavior. Mothers assigned to the control condition received no
      such training. Degree of maternal coordination was then assessed. Child
      compliance during a pick-up task was also assessed. Compared to controls,
      experimental mothers had significantly higher scores on several measures of
      maternal coordination and experimental children were significantly more
      compliant. The relation between parental coordination and child socialization is
      discussed.

PMID- 11845653
TI  - A comparison of two self-report measures of children's social anxiety in clinic
      and community samples.
AB  - Examined the relations between the Social Phobia and Anxiety Inventory for
      Children (SPAI-C) and the Social Anxiety Scale for Children-Revised (SASC-R) in
      community (n = 178) and clinic (n = 57) samples. A large proportion of children
      exceeded the recommended SPAI-C and SASC-R cutoffs for suggesting clinically
      significant levels of social phobia and social anxiety in the community (37% SPAI
      C and 20% SASC-R) and clinic (58% SPAI-C and 42% SASC-R) samples. A large
      proportion of children scoring in the clinical range on the Child Behavior
      Checklist (CBCL) exceeded the SASC-R and SPAI-C cutoff scores; however, there was
      notable variability with respect to sample, age group (< or = 10 years and > or =
      11 years), sex, and measure (SPAI-C vs. SASC-R, and CBCL Internalizing vs. Social
      Competence scale). Using the recommended cutoffs, discriminant function analyses
      found the classification correspondence between the SPAI-C and SASC-R was
      significant, with some variability found in the 2 samples, age groups, and sexes
      (ranging from 82% to 91% classification correspondence). These initial findings
      highlight a need to consider sample, age, and sex in further examination of the
      utility and validity of these measures and their recommended cutoffs.
      Implications for future work examining the linkages between social anxiety and
      social phobia, as well as for the assessment of children's social anxiety and
      social fears, are discussed.

PMID- 11845654
TI  - How children experience brief-exposure treatment of specific phobias.
AB  - Examined how 56 children who had received brief-exposure treatment for specific
      phobias experienced the treatment. It was also investigated whether there was a
      relation between the children's reported experiences before, during, and after
      the treatment and therapy outcome. Results indicated that the treatment was
      experienced as something positive, and the large majority of the children
      appreciated the pace and degree of control they had during treatment, as well as
      the therapist and the treatment outcome. The response patterns did not differ
      between sexes, diagnostic groups, mode of treatment, or age groups. The therapy
      outcome of the children was not found to differ according to the children's
      pretreatment expectations and feelings during the treatment, neither according to
      the children's evaluations of the pace of the treatment nor of the therapist's.
      However, children's reports about their feelings upon termination of the
      treatment and the satisfaction with the treatment differed significantly
      depending on the treatment outcome. Results and tentative explanations of these
      are discussed and implications for future lines of research are suggested.

PMID- 11845655
TI  - The Dutch Childhood Anxiety Sensitivity Index: psychometric properties and factor
      structure.
AB  - Examined the reliability, validity, and factor structure of the Childhood Anxiety
      Sensitivity Index (CASI; Silverman, Fleisig, Rabian, & Peterson, 1991) in a Dutch
      sample. Five hundred forty-four Dutch schoolchildren between 8 and 16 years of
      age completed Dutch translations of the CASI; the State-Trait Anxiety Inventory
      for Children (Spielberger, Edwards, Lushene, Montuori, & Platzek, 1973); and the
      Fear Survey Schedule for Children-Revised (Ollendick, 1983). The Dutch CASI was
      found to have adequate internal consistency for use with children as well as
      adolescents. Results reveal that the CASI predicted fear beyond a measure of
      trait anxiety in this Dutch sample. Both exploratory and confirmatory factor
      analyses comparing different models were undertaken. The model with 3 first-order
      factors found in previous studies showed an acceptable fit in this cross
      validation sample. Loadings on the 3 factors (Physical Concerns, Mental Concerns,
      and Publicly Observable Concerns) did not differ between children and
      adolescents. Results are compared with previous research on the CASI. Directions
      for future research are discussed.

PMID- 11845656
TI  - The ethical constraints of fraud & abuse regulations.

PMID- 11845657
TI  - Bioterrorism update: "maintain a high index of suspicion".

PMID- 11845658
TI  - Loss prevention case of the month. System failure--big time.

PMID- 11845659
TI  - Access MedPlus claims deadline fast approaching.

PMID- 11845661
TI  - AIDS centers of excellence.

PMID- 11845660
TI  - Rhabdomyolysis associated with pneumococcal pneumonia: an early clinical
      indicator of increased morbidity?
AB  - Rhabdomyolysis most commonly results from crushing injuries, the toxic effects of
      drugs and alcohol, seizures, and strenuous physical activity. Though
      rhabdomyolysis has been rarely identified with bacterial pneumonia, it has
      recently been recognized that in the setting of Legionella pneumophila pneumonia
      it has important prognostic implications. In the English literature, there are 12
      well-documented cases of rhabdomyolysis associated with Streptococcus pneumoniae
      pneumonia. Interestingly, in the majority of these patients, including ours, S.
      pneumoniae grew from their blood. Bacteremia in patients with S. pneumonia
      doubles the death rate. Nine of the 12 patients, ours included, with S.
      pneumoniae pneumonia associated rhabdomyolysis developed renal dysfunction, as
      evidenced by an elevation in their blood urea nitrogen (BUN) and serum
      creatinine. Uremia also indicates a poor prognosis in patients with pneumococcal
      pneumonia. Serum creatinine phosphokinase (CPK) is a simple test that may allow
      early recognition of S. pneumoniae pneumonia in patients who are at an increased
      risk for a poor outcome, and permit timely therapeutic intervention.

PMID- 11845662
TI  - Duty to warn and/or protect third parties.

PMID- 11845663
TI  - 41st. Bailey K. Ashford Memorial Lecture. Medicine in the 21st century:
      fulfilling the social contract.

PMID- 11845664
TI  - The contribution of immunohistochemistry in the diagnosis of pediatric neoplastic
      lesions in the University of Puerto Rico, School of Medicine.
AB  - Immunohistochemistry has revolutionized the field of diagnostic pathology in the
      past fifteen years. Since then, it has been increasingly used as an adjunct to
      morphological diagnosis. The purpose of this retrospective analysis is to examine
      the value of this technique in the diagnosis of pediatric neoplasias in our
      laboratory. Forty eight pediatric cases, collected from January 1998 until May
      1999, were reviewed, and classified in one of four categories: confirmed the
      morphological diagnosis, provided the definite diagnosis from a list of probable
      diagnoses, contributed by excluding other entities, and non-contributory.
      Immunohistochemistry confirmed the morphological diagnosis in 29 cases (60.4%),
      provided the definite diagnosis from a list of probable diagnoses in 13 cases
      (27.1%), was contributory by exclusion of other entities in 2 cases (4.2%), and
      was non-contributory in 4 cases (8.3%). In this preliminary study, we conclude
      that immunohistochemistry is being used in our laboratory mostly as a
      confirmatory tool for the definitive diagnosis of the lesions and once more
      exalts the utility of this technology in the field of diagnostic pathology.

PMID- 11845665
TI  - Dengue in children: critical points in management.
AB  - Dengue fever (DF) is endemic and occasionally epidemic in many tropical and
      subtropical areas inhabited by the mosquito vector Aedes aegypti. Infection with
      Dengue may present with varied clinical manifestations. Significant morbidity and
      mortality can result if early recognition and monitoring of its severe forms (DHF
      and DSS) is not done and if appropriate medical intervention is delayed. This
      article reviews several critical points in the basic evaluation and management of
      dengue in the pediatric age group and present our current approach in the form of
      a therapeutic algorithm.

PMID- 11845666
TI  - High incidence of emergency cesarean section among fetuses with unrecognized
      chromosomal abnormalities.
AB  - OBJECTIVE: To examine the incidence of obstetric complications in fetuses with
      unrecognized chromosomal anomalies compare with those in which the diagnosis was
      known before hand. METHODS: All cases followed at a private facility in San Juan,
      PR during the time from January 1993 through February 1997 were evaluated in
      terms of gestational age and method of diagnosis and eventual pregnancy outcome.
      RESULTS: There where 9 cases of chromosomal anomalies documented by karyotype
      analysis among 1377 (0.65%). Among this group, 5 cases were detected by a
      combination of maternal serum screening, analysis of risk factors and sonography.
      Among these, 3 cases elected pregnancy termination, one case of trisomy 21 was
      delivered stillborn vaginally at 32 weeks and one case of trisomy 18 delivered
      vaginally at 29 weeks. Among the 4 cases not recognized prenatally, one case of
      trisomy 21 was delivered at 27 weeks by classical cesarean section due to
      malpresentation and 3 cases (2 of trisomy 18 and one trisomy 21) where delivered
      by emergency transverse cesarean section due to suspected fetal hypoxia.
      CONCLUSIONS: The very high frequency of emergency cesarean section (100%) among
      fetuses with unrecognized major chromosomal anomalies should make us increase our
      efforts to obtain at prenatal diagnosis. In all of these cases, a prior diagnosis
      would have probably avoided a cesarean section and the associated potential
      maternal morbidity. PRECIS: The high incidence of emergency cesarean section
      among fetuses with unrecognized chromosomal anomalies should make prenatal
      diagnosis of these conditions a primary goal.

PMID- 11845668
TI  - Comparison of neonatal hearing screening devices.
AB  - Incidence studies estimate that 1-3 per 1000 full term normal neonates and 2-4%
      of high-risk newborns per 100 have severe bilateral hearing loss. In response,
      universal hearing screening has been proposed; however, choosing the most
      appropriate technology continues to be an obstacle. The purpose of the current
      preliminary study was to compare test results from thirty-two full-term newborns
      using three types of screening devices, Natus Algo 2 AABR, Otodynamics EchoCheck
      TEE, and Biologic AuDx DPE. Results indicate that the Natus had the highest pass
      percentage rate for the right and left ears at 97% and 91% respectively, while
      the other two devices had pass percentage rates between 31% and 56%. Test
      duration time for the Natus was 22.5 minutes compared with 5.8-6.4 minutes for
      the other devices. Despite the longer duration time, our findings favor using the
      Natus, given its accurate representation of incidence data.

PMID- 11845667
TI  - Knowledge and beliefs of breast cancer among elderly women in Puerto Rico.
AB  - This is the first national study of breast-cancer knowledge, beliefs, and early
      detection practices among elderly women (65+) in Puerto Rico. Cancer breast
      examination (CBE) was the most common early detection practice, followed by the
      mammogram, with breast self exam (BSE) a distant third. The primary reasons most
      often cited for never having a mammogram related to both personal and external
      factors: not having symptoms, negligence or forgetfulness, and not having a
      physician's referral. No statistically significant difference (p < 0.05) was
      found between knowledge and early detection practices. Conversely, beliefs had an
      impact on preventive behavior. Those who had less misconceptions were most likely
      to have had a CBE or a mammogram. Bivariate analysis demonstrated that age was
      associated with performing a BSE once or twice monthly, ever having a mammogram,
      and having a mammogram in the past two years. A higher socioeconomic status was
      associated to performing BSE and ever having had a mammogram. Education
      correlated positively to ever having a mammogram or having a mammogram in the two
      years prior to the interview. Factors that explained compliance with a mammogram
      in the last two years included referral from a physician, owning a car, and
      receiving information after menopause on breast cancer from a health care
      provider. A gynecological visit increased the probability of having had a
      mammogram during the last two years. Logistic regression determined that a
      referral from a physician was the most important factor for mammogram compliance
      when a combination of variables were considered.

PMID- 11845669
TI  - The social factors affecting the diffusion of parasitology to Puerto Rico and
      Hong Kong.
AB  - This study seeks to understand the role played by social factors in the diffusion
      of parasitology to Puerto Rico, in particular those affecting the work of Bailey
      K. Ashford between 1898-1934. Most studies of Ashford to date focus mainly on the
      intellectual framework per se, and rarely on the surrounding social environment.
      In order to achieve this aim, Ashford's experiences were contrasted to those of
      Patrick Manson in Hong Kong and China between 1866 and 1889. By undertaking this
      comparative approach, it became clear that social factors more significantly
      affected the advancement on their respective investigations than intellectual
      ones. Manson simply did not have the political and financial support needed to
      develop his work, hence greatly delaying the establishment of a research
      institute in Hong Kong, or China for that matter. By contrast, Ashford achieved a
      great deal of popular and congressional support, thereby enabling him to
      establish a research institution early in the century. Relevant social factors
      included: cultural differences, their history of colonial relations and the local
      economy.

PMID- 11845670
TI  - Profile of calls to a breastfeeding clinic information and help telephone line.
AB  - Breastfeeding mothers need orientation and help in order to succeed with
      breastfeeding. Lack of support from health professionals and societal barriers
      result in a median duration of breastfeeding in Puerto Rico of only 3 weeks. A
      telephone warm line at our breastfeeding clinic tries to provide some much-needed
      support and orientation. The purpose of this study was to determine the principal
      reasons for calls to the warm line and the action taken by the counselor. Five
      hundred and thirty three calls were received in a 4-month period. They were
      handled by certified lactation educators who gathered demographic and feeding
      information from the mother and registered the action taken. Descriptive analysis
      was used with crosstabs tables and multi-response analysis; chi-square test was
      used to establish the association between variables. 78.7% of callers were
      breastfeeding fully, while 21.3% were breastfeeding partially or formula feeding,
      62.8% of the babies were 2 months old or less. 68.8% of the calls originated in
      the metropolitan San Juan area. The source of the referral was family/friend in
      64.2% of calls, while only 9.8% of the callers were referred by a physician, 3.0%
      by hospital personnel and 2.0% by other health care providers. Significant
      differences between full breastfeeders and partial or artificial feeders were
      found in calls related to position (p = 0.01), engorgement (p = 0.04), breast
      refusal (p = 0.001), product information (p = 0.02), medications (p = 0.009),
      breastmilk management and storage (p = 0.001), and relactation (p = 0.02).
      Actions taken by the counselor included orientation, referral to breastfeeding
      specialist physician and referral to breastfeeding support groups or classes.
      Results indicate that more active promotion of referral to breastfeeding support
      groups or classes is warranted since this action was taken in only 14.5% of fully
      breastfeeding mothers and 12.6% of partial breastfeeding or formula users.
      Promotion of the warm line among physicians, hospitals and other health care
      professionals is also needed.

PMID- 11845671
TI  - [Kidney patients: aspects related to compliance with renal treatment].
AB  - The Objective of this study was identify the aspects related with the adherence
      of medical treatment recommended to the patients that received hemodialysis in
      the tertiary public hospital. A non experimental transectional correlation design
      was utilized in this study. Fifty-three patients constituted the population
      study. A structure interview was utilized to gathered the data. Descriptive
      statistics and Chi-square tests were utilized to analysis. The response rate was
      91.0%. The 75.0% of patients not compliance with the medical treatment.
      Significant association between compliance variable and educational level was
      encountered (p < or = 0.05). This study provides important findings to will
      develops educative intervention in the Renal Unit, directed to improve the
      adherence of the patient with medical treatment.

PMID- 11845672
TI  - [Factors associated with the level of anxiety of nursing personnel taking care of
      HIV positive patients].
AB  - The objective of the study was to measure the level of HIV/AIDS related anxiety
      among hospital nursing staff and identify its determinants. Data were obtained
      through anonymous self administered questionnaire distributed to 222 nurses. The
      rasge anxiety and the HIV/AIDS attitudes were the most determinants of the
      anxiety level in the participants. Specifically, negative HIV/AIDS attitudes was
      associated with raise in state anxiety level, as well as high level of rasge
      anxiety was associated with high level of state anxiety. In conclusion, it is
      necessary to provide to the participants update trainings that included different
      aspects of HIV infection, as well as, anxiety management when caring for persons
      with HIV/AIDS.

PMID- 11845673
TI  - To be a patient.

PMID- 11845675
TI  - Lateral elbow tendonopathy: a less inflammatory term than lateral epicondylitis,
      tennis elbow or workers' elbow.

PMID- 11845674
TI  - Anticipating and preventing delirium.
AB  - Delirium is one of the most common complications in elderly hospitalized
      patients. It is a predictor of poor prognosis. Despite its high incidence,
      studies have shown that physicians fail to detect at least half of all cases of
      delirium. This presentation will briefly discuss the diagnostic criteria
      according to the fourth edition of Diagnostic and Statistical Manual of Mental
      Disorders, the incidence and characteristics of delirium. It will then go on to
      discuss in more detail risk factors that assist in anticipating the development
      of delirium. Finally, attention will be given to specific interventions to use
      with patients in high-risk categories with the goal of preventing the development
      of delirium in these individuals.

PMID- 11845676
TI  - Acute pancreatitis secondary to isotretinoin-induced hyperlipidemia.
AB  - Isotretinoin is a vitamin-A derivative most commonly utilized in the treatment of
      severe recalcitrant nodulocystic acne. Derangement of lipid metabolism leading to
      increased triglyceride and cholesterol level has been reported after taking this
      drug. We report the case of a 43-year-old female with no identifiable risk factor
      for pancreatitis who developed acute pancreatitis associated with hyperlipidemia
      while being treated with isotretinoin for hidradenitis suppurativa. To our
      knowledge, this is the third reported case of isotretinoin-induced hyperlipidemia
      leading to acute pancreatitis.

PMID- 11845678
TI  - Small LDL and hsCRP as new risk factors for coronary artery disease.

PMID- 11845677
TI  - State Children's Health Insurance Program.
AB  - Despite a number of efforts by states and the federal government over several
      years, millions of low-income children still lack health insurance coverage and,
      therefore, have limited access to healthcare services. To address these problems,
      Congress has created, and states are now implementing, the new State Children's
      Health Insurance Program (SCHIP). Policymakers and agency officials who design,
      operate, and sponsor health coverage programs such as SCHIP must determine what
      constitutes an effective program. Efforts to maximize the number of children with
      coverage are important. The challenge for each state and its communities is to
      effectively identify and enroll eligible low-income children. They must create
      outreach strategies to find and enroll children in Medicaid and SCHIP. However, a
      truly effective program must go beyond simply enrolling children in health
      coverage programs. They must also assure that newly enrolled children receive
      quality comprehensive health care.

PMID- 11845679
TI  - The management of supraventricular tachyarrhythmias. Primary care considerations.

PMID- 11845680
TI  - The use of electron beam computed tomography in the primary care setting.
AB  - EBT has become a clinical tool that has allows physicians to gain another piece
      of data to help predict which patients may be at risk for coronary artery
      disease. Valuable information that predicts a patient's risk at a relatively
      young age (fourth or fifth decade) may allow attenuation of such risk by
      aggressive risk factor modification over the ensuing decades. Coronary calcium
      can be quantified and subsequently followed to see if risk factor modification is
      effective. The task for the primary care physician is to properly use these new
      imaging tests to improve the care they provide for their patients.

PMID- 11845682
TI  - Managing patients with "refractory" heart failure.

PMID- 11845683
TI  - Overview of endovascular and open abdominal aortic aneurysm repair.

PMID- 11845681
TI  - Preclinical cardiovascular research projects and capabilities at the Atlanta
      Cardiovascular Research Institute.
AB  - The professional and technical staff of the Atlanta Cardiovascular Research
      Institute preclinical laboratory facility are aggressively pursuing basic and
      applied research to aid in the understanding of cardiovascular disease and
      develop new therapeutic approaches. We are optimistic that our intense and broad
      ranging research efforts will contribute to important advances in the care of
      cardiovascular disease patients in the near future and for years to come.

PMID- 11845684
TI  - Recent advances in interventional cardiology.

PMID- 11845685
TI  - [Status of blood supply to the eye in patients with primary open-angle glaucoma
      depending on the value of systemic arterial pressure and level of ophthalmic
      tone].
AB  - Blood supply to the eye was studied in 756 patients aged 40-82 years (1339 eyes)
      with primary open-angle glaucoma, systemic arterial pressure (AP) 105-170 mm Hg,
      and various level of intraocular pressure (IOP). Control group consisted of 340
      healthy subjects (680 eyes) aged 28-80 years without ophthalmic diseases with the
      same AP values. Blood supply values in the controls were taken for the norm. They
      were in high correlation with systemic AP. Ocular blood supply in patients with
      primary open-angle glaucoma depends on systemic AP and IOP, particularly
      perfusion pressure (Pperf) which decreases by 3.1 mm Hg in patients with systemic
      AP of 126-139 mm Hg and moderately (from normal to moderate) increased IOP. If
      IOP increases in the interval from moderate to high in patients with the same AP,
      Pperf drops by 12.5 mm Hg. Pperf values indicate deterioration of ocular blood
      supply in patients with primary open-angle glaucoma and different levels of IOP.

PMID- 11845686
TI  - [Effect of optic aberrations, caused by ablation pattern decentration after laser
      vision correction, on visual acuity].
AB  - The aim of this work was to study the effects of subclinical ablation pattern
      decentration on the quality of vision after photorefractive laser surgery.
      Optical high order spherical and coma-like aberrations of 30 eyes were evaluated
      before, 1 and 3 months after photorefractive surgery (PRK and LASIK).
      Relationship between the size and shape of the light spot on the retina during
      transmission of paraxial beams through the eye and the ablation zone
      decentrations was estimated. The results are presented for pupil diameters of 1
      and 6 mm both at the center of the retina along the optical axis and at a
      distance of 0.5 mm from the center. Decentration of ablation zone by less than 1
      mm makes the principal contribution to induction of higher order aberrations. The
      relative increase factor is 3.9 and 5.1 for the coma-like and spherical
      aberrations, respectively. At such decentrations spatial resolution of the eye
      decreases as the pupil size increases, which is most pronounced even at a slight
      distance from the visual axis but inside the fovea.

PMID- 11845687
TI  - [Cases of eye trauma after laser keratomileusis].
AB  - Variants of corneal injuries and their complications in various periods after
      laser keratomileusis are described. The causes and probable mechanisms of
      injuries are analyzed with consideration for pathohistological findings. A total
      of 3507 operations were performed in 1796 patients with myopia of 1.5-14.5
      diopters. Hansatome microkeratotome was used for lamellar section of the cornea
      and EC 500 eximer laser (Nidek) for laser keratoablation. According to the
      consultation rate, the incidence of injuries was 0.45% (16 eyes). The injuries
      occurred 1 week to 6 months after the operation and were as follows: epithelial
      injuries (10 cases), foreign bodies in the cornea (4 cases), and displacement of
      corneal flap (2 cases). The causes of injuries were mainly communal, the outcomes
      were favorable, microsurgical reoperation was needed in 3 cases. The mechanisms
      of injuries were analyzed with consideration for the histology of human cornea.
      The most complete fixation of corneal flap after laser keratomileusis was
      attained in the wound channel and at the site of the flap stromal apposition.
      Mechanical displacement of the corneal flap resultant from the injury is the most
      probable during the 4-week formation of cicatricial tissue in the wound; later
      the direction of the traumatic agent is significant. Prevention of corneal
      injuries after laser keratomileusis is important.

PMID- 11845688
TI  - [Acoustic studies in proliferative diabetic retinopathy].
AB  - Based on analysis of published reports and his own experience of acoustic studies
      (B-method) in more than 500 patients with proliferative diabetic retinopathy, the
      author concludes that preretinal fibrovascular membranes (posterior detachment of
      the hyaloid membrane with neovascularization) are often mistaken for retinal
      detachment. Acoustically detected solitary or multiple adhesions between
      fibrovascular and eye membranes are an important differential diagnostic sign
      indicating the absence of retinal detachment. These adhesions result from gradual
      staged "creeping" posterior vitreal detachment and indicate the sites of previous
      contact of the hyaloid membrane with the retina. In subtotal detachment of the
      retina there are no adhesions with ocular membranes and the retina acquires the
      configuration of a rigid fibrovascular membrane.

PMID- 11845689
TI  - [Role of ultrasonic B-scanning in differential diagnosis and prognosis of the
      course of optic neuritis].
AB  - The possibility of using ultrasonic scanning in differential diagnosis of optic
      neuritis (ON) and anterior ischemic neuropathy (AIN) and the prognostic
      significance of the results were evaluated. The thickness of retrobulbar part of
      the optic nerve directly behind the eye was measured by echographic B method in
      patients with ON and AIN. The thickness of the retrobulbar part of the involved
      and paired optic nerve was more than 0.7 mm in 90% patients with ON, which can be
      considered as an additional clinical sign of ON. Thickening of the retrobulbar
      part of the optic nerve is not characteristic of AIN. In patients with
      disseminated sclerosis ON is associated with less pronounced thickening of the
      retrobulbar part of the optic nerve than in idiopathic ON, which agrees with the
      pathogenesis and pathomorphology of disseminated sclerosis. The degree of optic
      nerve thickening in ON in patients with disseminated sclerosis is prognostically
      insignificant, while in idiopathic ON more than 2 mm asymmetry of the retrobulbar
      part of the involved and paired optic nerve is a sign predicting a long course of
      the disease and maybe incomplete recovery of vision. Thickening of the involved
      optic nerve by less than 1.7 mm is associated with a better prognosis as regards
      the time and completeness of vision restoration.

PMID- 11845690
TI  - [Psychophysical symptoms of demyelinating diseases of the optic nerve in multiple
      sclerosis].
AB  - Visual system channels were examined in 25 patients with multiple sclerosis. A
      new complex of symptoms was detected, reflecting the acute stage and the chronic
      demyelinizing process, which includes disorders of contrast, color, and spatial
      contrast sensitivity and stereoscopic vision. This can be useful in differential
      diagnosis of optic nerve diseases and evaluation of the visual system function in
      multiple sclerosis and prediction of the disease course.

PMID- 11845691
TI  - [Long-term results of surgical prevention and correction of progressive myopia].
AB  - In this summing-up paper the authors discuss the results of surgical prevention
      and correction of progressive myopia carried out at Department of Ophthalmic
      Diseases of Russian University of Peoples' Friendship during two recent decades.
      Remote results of bandaging scleroplastic and reduced chondroplastic operations
      recommend scleroplastic interventions for prevention of myopia progress. Combined
      scleroplasty and cataract extraction stabilized the elongation of the antero
      posterior axis of the eye and essentially improved visual acuity of 18-20
      diopters. New variants of interlamellar operations are presented: tunnel-circular
      and fragmented circular, which are protected by patents of the Russian
      Federation. These operations are recommended for patients with stable myopia of 8
      15 diopters after scleroplasty. Their advantage is low traumatism, absence of
      deep incisions on the cornea, wide optic center, possibility of regulating the
      refraction effect by replacing the implants or their complete removal without
      serious consequences for the cornea.

PMID- 11845692
TI  - [Effect of actipol on interferon level in tears (clinico-laboratory study)].
AB  - High interferon-inducing activity of a new antiviral drug actipol (0.007% para
      aminobenzoic acid) instilled into the eye was demonstrated in animal experiments.
      In the present study the effect of actipol on interferon production in ocular
      tissues was investigated clinically. Interferon (IFN) content was measured in
      washings from the conjunctiva in 20 patients with herpetic keratitis, treated by
      actipol. Actipol was instilled frequently or injected subconjunctivally
      parabulbarly. The reference group consisted of 7 patients with herpetic keratitis
      treated with acyclovir locally. IFN titer was the last dilution of the sample
      ensuring 50% cell protection in comparison with complete cell destruction in the
      virus control. The samples were collected before, on days 1, 2, 3, 7 of
      treatment, and after clinical cure. Time course of IFN concentrations was wave
      like in all the patients. The peak of IFN content surpassed the initial level 2-4
      fold in all patients (26.13 +/- 5.9 vs. 58.9 +/- 4.4 U/ml, p < 0.01), which seems
      to be due to actipol induction of IFN production in the surface structures of the
      eyeball. In the reference group IFN content did not increase in comparison with
      the control during treatment. Hence, actipol induces the production of IFN in the
      surface eyeball structures in patients with various forms of herpetic keratitis.

PMID- 11845693
TI  - [Experimental study of infrasonic phonophoresis].
AB  - A new method of drug administration, infrared phonophoresis, was experimentally
      studied. The method has no analogs in the world. The study was carried out on 20
      Chinchilla rabbits. Water applications impregnated with equal volumes of the
      radiopharmaceutical (RP) were placed into the conjunctival cavities of both eyes.
      The right eye was control and the left was treated by infrasound (experiment).
      The information was recorded in live animals after removal of the application and
      thorough washing of the conjunctival cavity immediately, 30 min, and 1 h after
      infrasound phonophoresis session. Radioactivity measurements at all terms
      indicate its stable increase in the experimental eye and a progressive decrease
      in the control eye. Hence, infrasound promoted long accumulation of the RP in the
      eye at anterior route of the drug delivery without preliminary injection of the
      drug into ocular vessels.

PMID- 11845694
TI  - [Functional methods of research in diagnosing glaucoma].
AB  - New data on the function of the retinal cone system in glaucoma are presented,
      which extend the symptom complex of optic neuropathy of glaucoma origin and the
      potentialities of initial diagnosis of glaucoma. A new symptom is detected:
      disordered topography of color (red and green) sensitivity, which can serve as
      the early symptom of glaucomatous optic neuropathy and indicate the degree of its
      progress. The location of the process, detected in examination of color
      sensitivity topography, is more extensive than it is detected by static
      perimetry. Primary location of functional disorders is detected in the parafoveal
      area and the disorders are the more severe the further from the center during the
      initial stage of glaucoma. As the process progresses, the central zones are
      involved in it.

PMID- 11845695
TI  - [Features of retinal hemodynamics and the optic nerve in developing primary
      atrophy in tumors of the chiasmal-sellar area].
AB  - The pathogenesis of primary optic atrophy of different severity, caused by tumors
      in the chiasmal-sellar area is analyzed as exemplified by 109 patients. The
      severity of primary optic atrophy depended on the duration of visual disorders.
      The patients were divided into 2 groups with early and late stages of visual
      disorders. Use of objective methods of examination (fluorescent angiography,
      densitometry, and fluorophotocalibrometry) helped detect the earliest changes in
      the fundus oculi microcirculation, accurately determine the severity of optic
      atrophy, and more completely evaluate the hemodynamic disorders in the ocular
      artery system.

PMID- 11845696
TI  - [Combined treatment of cyclotropia].
AB  - A protocol of combined treatment of patients with cyclotropia has been developed,
      including surgery and functional treatment by an original method. Combined
      treatment of cyclodiplopia and forced compensatory head turn (ocular torticollis)
      led to complete restoration of solitary vision in the entire visual field in 12
      (34%) cases, in the main part of visual field in 20 (58%) cases, complete
      elimination of torticollis in 18 (52%) cases, and decrease of torticollis in 14
      (40%) cases. Hence, the proposed treatment protocol brings about good functional
      results and is recommended for the treatment of patients with cyclodiplopia and
      torticollis.

PMID- 11845697
TI  - [Excimer laser correction of post-traumatic corneal astigmatism on an
      "artiphakic" eye].
AB  - A unique clinical case is presented: LASIK in a 12-year-old child for correction
      of posttraumatic corneal astigmatism after penetrating wound of the eye and
      extraction of traumatic cataract with IOL implantation. The patient was observed
      for 3 months postoperation.

PMID- 11845698
TI  - [Glaucomatous optic neuropathy: pathogenesis, clinical picture, and new
      approaches to treatment].

PMID- 11845699
TI  - [Color Doppler mapping in ophthalmology].

PMID- 11845700
TI  - [Pigmented dispersion syndrome].

PMID- 11845701
TI  - [Albrecht von Graefe--an outstanding German ophthalmologist (his life, medical
      and scientific activities)].

PMID- 11845702
TI  - [Risk factors for developing exudative reactions and fibrosis of the rear capsule
      after cataract extraction with implantation of an artificial lens].
AB  - A total of 132 patients were observed after cataract extraction with implantation
      of T-26 polymethacrylate and RSP-1 collagen copolymer intraocular lenses. Factors
      of risk of postoperative exudative reaction and fibrosis of the posterior capsule
      were determined, which depend on previous ophthalmic diseases (glaucoma, uveitis,
      diabetic angioretinopathy) and concomitant acute and chronic diseases of other
      organs (bronchopulmonary system, collagenosis, cholecystitis). Moderate changes
      in the hemogram before surgery are worthy of note.

PMID- 11845703
TI  - [Delayed radiation-induced optic neuropathy in patients with tumors in the
      chiasmal-sellar area after radiation therapy].
AB  - Six clinical observations of a rare condition, delayed radiation-induced optic
      neuropathy (RON) are presented. RON developed in patients with brain tumors
      treated by radiotherapy and radiosurgery; in the majority of patients the
      condition developed during exposure to therapeutic doses; its incidence was 0.5%
      of the total number of patients treated by radiotherapy during this period.
      Asymmetrical chiasmal syndrome developed rapidly in all the patients. Clinical
      diagnosis of RON was confirmed by magnetic resonance tomography in all cases, and
      in one case by morphological analysis. Conservative therapy including hyperbaric
      oxygenation just stabilized the visual function. Remote period of observation was
      42 months.

PMID- 11845704
TI  - Developing and implementing clinical practice tools: the legal and ethical
      implications.
AB  - The complexity of health care is ever increasing, as is the volume of research
      and literature available. In response there has been a corresponding emphasis on
      basing clinical decisions on the best available research evidence. The
      development and implementation of clinical practice tools is cited as a means of
      ensuring research utilisation as well as moderating variations in clinical
      practice. It is important that nurses contribute to the development of these
      clinical tools in order to actively shape their own practice. Nurses therefore
      need to have an understanding of the terminology and processes involved, and the
      implications for practice. This paper outlines definitions of the various
      clinical tools, the development process, and the legal and ethical implications
      of clinical practice tools.

PMID- 11845705
TI  - Difficulty in removing suprapubic urinary catheters in home based patients: a
      comparative descriptive study.
AB  - The aim of the study was to monitor difficulties being experienced by community
      nurses when removing suprapubic catheters in 94 patients living in two area
      health services in Sydney. The study identified one catheter brand (Simpla) that
      was associated with more pain and bleeding for patients, and increased
      difficulties in removal for the nurses. It was found that muscle relaxant
      medications taken by patients contributed significantly in ease of catheter
      removal. In over 50% of all-silicone catheters surveyed, there was evidence of
      hysteresis leading to balloon cuffing on deflation. This phenomenon could be
      associated with increased trauma to the suprapubic cystostomy tract on catheter
      removal. A review of the risks and benefits associated with all-silicone
      catheters used for suprapubic insertion is recommended.

PMID- 11845706
TI  - The dynamics of coping and adaptating to the impact when diagnosed with diabetes.
AB  - The coping trajectory of a group of people who were insulin dependent (Type 1
      diabetes n = 109) was compared with that of a group people who were non-insulin
      dependent (Type 2 diabetes n = 241). The experience of the diagnosis of diabetes
      mellitus (DM) was different for both groups. Type 1 people were more likely to
      feel the impact of the diagnosis more severely than Type 2 people and were more
      likely to use avoidance, denial and fantasy strategies in their attempts to cope
      with the diagnosis and its implications. The residual effects of not being ill
      were more likely to be felt by Type 2 group. Those who showed determination not
      to be beaten by the disease tended to use more positive coping techniques in
      making the adjustment. Illustrative path diagrams for both the Type 1 and Type 2
      groups are presented. Health professionals need to recognise the likely
      differences in order to provide the most appropriate care.

PMID- 11845707
TI  - A study of the relationship between quality of life, health and self-esteem.
AB  - In this study, 757 participants reported data on quality of life (QOL), health
      and self-esteem. Findings indicated that older people experienced higher QOL than
      people in other age groups. Variables contributing to higher QOL include having
      good relationships with their partner, with their children, and God. Caring for
      others, or carrying a disability or illness diminished QOL scores. High positive
      self esteem scores were important in overall indices of QOL. High positive self
      esteem and an absence of negative self esteem were substantial contributors to
      the 'happiness' dimension of QOL. Having a good sex life, or not having sex was
      more important than having poor sexual relationships. QOL has been an important
      concern for nurses in terms of the relationship between individual health and
      QOL, but there is a need to broaden the perspective from which QOL is viewed.

PMID- 11845708
TI  - Reflections on nursing.

PMID- 11845709
TI  - Patient falls from bed and the role of bedrails in the acute care setting.
AB  - The use of bedrails in preventing patient falls from bed remains highly
      controversial and has received only limited research attention throughout the
      last decade. The present study questioned the relationship between bedrail use
      and patient falls from bed particularly in terms of age-gender characteristics,
      mental status and the severity of injuries sustained. A retrospective, cross
      sectional analysis was conducted of 419 patient falls occurring in an urban,
      acute care hospital from 1993-2000. This audit identified 136 falls from bed. It
      was found that for all age-gender groups the incidence of falls from bed with
      bedrails elevated was equal to or higher than when bedrails were not elevated.
      Patients in a 'non rational' state at the time of falling were significantly more
      likely to have fallen with the bedrails elevated (chi 2 = 19.463, p < 0.001).
      Whilst there was no statistically significant relationship between the position
      of bedrails and the severity of injuries sustained (chi 2 = 1.088, p = 0.780) the
      fact that there was a patient death resulting from a fall from bed over elevated
      bedrails was considered to be of particular clinical significance. Thus the role
      of bedrails as protective or safety devices was challenged and an urgent re
      evaluation of current practices recommended.

PMID- 11845710
TI  - [Basic medico-demographic parameters of development of children and adolescents
      in Moscow].

PMID- 11845711
TI  - [Methodological approaches in developing disease prevention in mine workers in
      northeast Russia].
AB  - For many years the Magadan region occupies the leading position as regards the
      incidence of occupational and some general somatic diseases. Recent social and
      economic reforms in mining industry led to a decrease in the level of life of
      workers and their family members and an increase in the incidence of professional
      and general somatic diseases and mortality of capable people. Improvement of
      socio-hygienic conditions of miners' life at the expense of enterprises of new
      forms of property can be hardly expected in the nearest future, which
      necessitates realization of a complex regional program taking account of economic
      specificities of the region, aimed at improvement of total resistance to
      unfavorable climatic conditions of the North.

PMID- 11845712
TI  - [Socioeconomic aspects of reforming pediatric dental care in Moscow].

PMID- 11845713
TI  - [Improvement of medical-social expertise and rehabilitation of invalids as a
      result of circulatory system diseases].
AB  - Presents information on the creation of norm-setting legislative, legal,
      organization and structural, functional, research and methodological basis for
      the development and perfection of medicosocial expert evaluation under conditions
      of changed methodology of expert work and transition from medical labor to
      medicosocial expert evaluation.

PMID- 11845714
TI  - [Some problems in health status of residents of the Russian Federation].
AB  - This paper sums up the effect of socio-economic crisis developing in the country
      in the nineties on the population health. Based on analysis of the status and
      time course of medico-demographic processes, morbidity, and physical development,
      the author demonstrates the staged pattern in the formation of these values: each
      new exacerbation of the socio-economic situation augmented the negative changes
      in comparison with the previous high level.

PMID- 11845715
TI  - [Problems of organizing home nursing].
AB  - Nursing has been practiced for centuries. Public health reformation suggests
      further development of nursing care, particularly at the level of primary health
      care, and improvement of the status of a nurse in the society and her role in the
      public health system. Outpatient forms of nursing care are regarded as the most
      effective nurse's services. Nurses' functions within the framework of primary
      health care are extended to include therapy and diagnosis, rehabilitation,
      medicosocial care, and disease prevention. The main tasks in the development of
      nursing are improvement of the quality of nurses' services, renaissance of the
      charity traditions, increase of the profession prestige and improvement of
      training.

PMID- 11845716
TI  - [Prevention of disability in major cardiovascular diseases].

PMID- 11845717
TI  - [Outpatient psychiatric and substance abuse help in the Republic of Ingushetia].
AB  - Psychiatric service regards the "Home hospital" model as one of the optimal
      methods for organization of therapeutic and prophylactic work under present-day
      day socio-economic conditions and migration processes in the Republic. Prospects
      for further development of this model are outlined.

PMID- 11845718
TI  - [Dynamics of developing outpatient facilities in the Republic of Tatarstan].

PMID- 11845719
TI  - [Medical care for residents of Ulan-Bator and problems of public health care
      management].

PMID- 11845721
TI  - [Reform in rural health care after the Second World War].

PMID- 11845720
TI  - [M. Ia. Mudrov and establishment of clinical training at Moscow University (on
      the 225th anniversary of the birth of M. Ia. Mudrov, 1776-2001.) Report I. Letter
      to M. N. Murav'ev (1805)].

PMID- 11845722
TI  - [Management of health care in February-October 1917].

PMID- 11845723
TI  - [N. F. Freiberg--visible organizer of domestic health care].

PMID- 11845724
TI  - [From the history of medicine of Kabardino-Balkaria].

PMID- 11845725
TI  - [Effect of potential population viability in active age on socioeconomic well
      being of society].
AB  - Loss of potential life man/years in the active period (16-69 years) is analyzed.
      353,453 man/years, 48.88% of these in the capable age, were lost in 1998 in the
      region. 30 births were not realized. Although females predominate in the
      population, loss of males is much higher. The majority of deaths is due to
      exterior causes, circulatory diseases, and tumors. However by the mean duration
      of lost potential per case, the main causes are infections, urinary diseases, and
      respiratory or gastrointestinal diseases. These data and further analysis for
      individual nosological entities will help improve the efficiency of public
      health.

PMID- 11845726
TI  - NHS direct: no cushy number.

PMID- 11845727
TI  - Antiepileptic drug overdose.

PMID- 11845728
TI  - Pathophysiology of sickle cell disease crisis.

PMID- 11845729
TI  - Benchmarking as a quality assessment tool.

PMID- 11845730
TI  - Assessing clinical competence.

PMID- 11845731
TI  - Audit of administration of analgesia.

PMID- 11845732
TI  - Cup-feeding for preterm infants: mechanics and safety.
AB  - Cup-feeding is recommended for breastfed preterm infants to avoid artificial
      nipples. However, the oral mechanisms used in cup-feeding, or its safety and
      efficacy, have not been described. The authors measured sipping, breathing, SaO2,
      and volume of intake during 15 cup-feeding sessions for 8 infants (mean
      gestational age at birth was 30.6 weeks). Mean duration of sipping bursts and
      pauses was 3.6 seconds and 28.1 seconds, respectively. Mean breathing rate during
      bursts and pauses was similar (46.2 +/- 24.3 vs 45.7 +/- 17.7, respectively),
      with SaO2 > or = 90% during all bursts. Mean duration of cup-feedings was 15.2 +/
      3.9 minutes (range, 11.0-23.3), whereas mean volume of intake was only 4.6 +/-
      2.2 mL (range, 1.5-8). For the 15 sessions, 38.5% of milk taken from the cup was
      recovered on the bib. Although infants remain physiologically stable, cup-feeding
      has questionable efficacy and efficiency. Differentiating between actual intake
      versus spillage of milk merits attention.

PMID- 11845734
TI  - Process evaluation of the Saskatoon breastfeeding center.
AB  - A process evaluation of the Breastfeeding Center in Saskatoon was conducted to
      assess clients' characteristics and satisfaction. Fifty women completed a
      questionnaire immediately after visiting the center and were interviewed by
      telephone 2 to 4 weeks later; another 25 women telephoned the center for
      information and were interviewed by telephone 2 to 4 weeks after initial contact.
      Four visits were observed and timed. Respondents were generally very satisfied
      with all aspects of the center. All said they would use the center again and
      recommend it to others. Most of the respondents were still breastfeeding when
      interviewed and felt that the center had helped them do so. Observation of the
      visits revealed a consistent sequence of activities, with visits taking longer on
      average than the time allotted. The evaluation confirmed that the center was
      meeting its process objectives. This evaluation could be used as a model for
      other community-based breastfeeding centers.

PMID- 11845733
TI  - Predicting early breastfeeding attrition.
AB  - The Breastfeeding Attrition Prediction Tool (BAPT) is based on the theory of
      planned behavior, which explains behavior as a function of attitudes, subjective
      norm, and perceived control. The BAPT subscales are positive and negative
      attitudes toward breastfeeding, family and professional expectations, and
      perceived ability to be successful. The purpose of this study was to test the
      reliability and validity of the BAPT among 269 women who planned to breastfeed
      for at least 8 weeks. Subjects completed the BAPT in the hospital and during a
      telephone interview at 8 weeks. Based on factor analysis, several items were
      deleted. Using discriminant function analysis, the modified BAPT was an effective
      predictor of 78% of women who stopped breastfeeding before 8 weeks and 68% of
      those who were still breastfeeding. There is potential for the modified BAPT to
      be an adjunct for the clinician in identifying women at risk for early cessation
      of breastfeeding.

PMID- 11845735
TI  - Breastfeeding initiation and duration among low-income women in Alabama: the
      importance of personal and familial experiences in making infant-feeding choices.
AB  - To gain perspective on breastfeeding initiation and duration among poor women in
      the southeastern United States, the authors interviewed a random sample of 150
      mothers (93% African American) at a county health clinic in Birmingham, Alabama.
      Forty-one percent of women initiated breastfeeding, 24% breastfed for at least 1
      month, and 8.3% breastfed for 3 months or more. Initiation of breastfeeding was
      positively associated with the mother having been breastfed herself and having
      breastfed a previous infant, and negatively associated with premature delivery.
      Breastfeeding at 1 month was more likely among older women and women with close
      relatives who breastfed. Duration of breastfeeding beyond 1 month was associated
      only with the mother having been breastfed and having breastfed a previous
      infant. Maternal and familial breastfeeding experiences eliminated the effect of
      more distal factors, such as income or education, on some feeding decisions. The
      strong influence of breastfeeding experiences must be considered in infant
      feeding interventions.

PMID- 11845736
TI  - Risk, research, and infant feeding recommendations.

PMID- 11845737
TI  - Colic and food allergy in the breastfed infant: is it possible for an exclusively
      breastfed infant to suffer from food allergy?

PMID- 11845738
TI  - Breastfeeding an infant after heart transplant surgery.
AB  - The case study describes an infant who was diagnosed 24 hours after birth with
      hypoplastic left heart syndrome, a cognitive malformation of the heart. He
      received a heart transplant 30 days later. The infant received breast milk before
      transplant and successfully breastfed after the transplant until the age of 13
      months. For the 5 years since the transplant, he has had no complications
      associated with hypoplastic left heart syndrome.

PMID- 11845739
TI  - Bottle-feeding as a tool to reinforce breastfeeding.
AB  - Babies may need supplementation due to difficulty breastfeeding. Others must be
      fed by alternative feeding methods because they are separated from mothers who
      have returned to employment or school. Recognizing that mothers and caregivers
      are often not comfortable using other alternative feeding devices, the author
      endeavored to develop a method of bottle-feeding that would meet the needs of
      these mothers and their babies without causing suck confusion. The resulting
      bottle-feeding method requires babies to expend effort and use their oral anatomy
      in ways very similar to breastfeeding.

PMID- 11845740
TI  - A description of a male-focused breastfeeding promotion corporate lactation
      program.
AB  - The role of the father has been identified as one of the strongest influences on
      the initiation and duration of breastfeeding by mothers in the United States.
      This report describes a corporate lactation program that focuses on promoting
      breastfeeding through male employees. Since 1990, a full-time on-site lactation
      program has been offered to male employees at the Los Angeles Department of Water
      and Power, a public utility company. The male program participants are from
      diverse backgrounds. Participation in the Fathering Program has grown since 1990
      based on word of mouth, fathers' interest in the benefits of breastfeeding for
      the infant, and the female partners' interest in getting a free pump rental. This
      report illustrates the viability of a breastfeeding support program that targets
      male employees and that is offered in a corporate setting.

PMID- 11845741
TI  - Maternal transplantation medications during breastfeeding.
AB  - Previously transplanted women have maintained successful pregnancies yet have
      been discouraged from breastfeeding. The American Academy of Pediatrics cautions
      against breastfeeding due to documented presence of cyclosporine in breast milk
      and unknown long-term effects on nursing infants. Transplant centers, however,
      report mothers breastfeeding with no measurable cyclosporine serum concentrations
      or untoward effects in their infants. Few data are available with regard to
      levels of other transplant medications in breast milk. Given the small number of
      published reports involving lactating women and relatively short follow-up of
      their infants, routine medication levels should be part of any screening regimen
      for such breastfed infants until further studies are available.

PMID- 11845742
TI  - Training peer counselors to promote and support exclusive breastfeeding in
      Bangladesh.
AB  - Exclusive breastfeeding is rare in Bangladesh. About 90% of women have home
      deliveries, so the Baby-Friendly Hospital Initiative has no mechanism to reach
      them. Mother support groups do not exist, and community health workers do not
      have time to promote and support exclusive breastfeeding. To provide this kind of
      support at the community level, an area in Dhaka was selected for a peer
      counseling intervention program. Using certain selection criteria, 1 woman from
      each community was trained as a peer counselor. The training was based on the
      World Health Organization/United Nations International Children's Emergency Fund
      40-hour breastfeeding counseling course and related books. Counseling skills were
      taught using demonstrations and role play, followed by practical training in the
      project area. The intervention was very successful, as 70% of the mothers in the
      project area breastfed their infants exclusively for 5 months compared to only 6%
      in the control area. The authors describe the peer counseling training,
      strategies used for peer counseling visits, and lessons learned.

PMID- 11845743
TI  - Winter planning. Seasonal cycles.
AB  - It is possible to forecast emergency admissions and bed requirements with
      considerable accuracy up to a year in advance. A model is being developed which
      would analyse the effects of weather, flu epidemics and different surges in
      demand. The discharge pattern of many hospitals indicates a rush to discharge by
      the weekend that could raise concerns about appropriate care.

PMID- 11845745
TI  - Intermediate care. Halfway home.
AB  - A pilot scheme involving 30 nursing home places provided intermediate care for
      118 elderly people over four months last winter. The average length of stay was
      21 days. Two-thirds of patients were discharged to their own home. Patients rated
      the nursing care highly. Concerns were raised about the availability of
      therapists.

PMID- 11845744
TI  - Hospital activity. Go with the flow.
AB  - A project to reduce cross-boundary referrals has shown GP referrals have less
      effect on hospital activity than first thought. A high proportion of cross
      boundary referrals are for procedures not carried out at local hospitals. The
      issues involved are complex and scope for reducing these referrals more limited
      than first believed.

PMID- 11845746
TI  - Enhancing lives through the development of a community-based participatory action
      research programme.
AB  - A community-based participatory action research (PAR) programme that has spanned
      5 years is discussed in this article. A primary healthcare philosophy requires
      research in this practice setting and supports the way healthcare is ideally
      organized within an integrated team and supported by a community network that
      includes not only the healthcare workers and service providers but also the
      community as partners. The principles driving three PAR inquiries are described:
      the development of a model for prevention of workplace violence; working with
      clinicians towards improving wound management practice; and management of
      continence for community-dwelling women living with multiple sclerosis.
      Participatory action research is a potentially democratic process that is
      equitable and liberating as participants construct meaning in the process of
      group discussions. We conclude that the cyclical processes inherent in PAR
      promote reflection and reconstruction of experiences that can lead to the
      enhancement of people's lives, either at an individual or community level, or
      both.

PMID- 11845747
TI  - Mental health issues in primary healthcare.
AB  - This article describes a project that was designed to explore mental health
      issues arising in primary care, as a basis for understanding primary care
      professionals' mental health training needs. Whilst recent UK government
      initiatives, such as the National Service Framework for Mental Health, have
      emphasized the need to enhance mental healthcare in the general population, the
      capacity to respond effectively is likely to be dependent upon primary care
      professionals acquiring the relevant skills. To achieve this, a thorough
      understanding of the issues inherent in dealing with mental health problems in
      primary care is required. Given that the mental health issues facing primary care
      professionals may differ from those that confront mainstream mental health
      professionals, logic dictates that primary care professionals may require a
      discrete set of skills and a special approach to mental health training. The
      principal aim of this project was, hence, to identify mental health issues
      arising in clinical practice, as a first step towards identifying primary care
      training needs. A series of focus groups and semi-structured interviews was used
      to gather information about mental health issues arising in primary care, based
      on the experiences of primary care professionals and users' representatives. The
      findings suggest that primary care professionals are confronted by a wide range
      of mental health issues, many of which lie outside of the scope of the current
      National Service Framework for Mental Health. The article discusses the
      implications for mental health training in primary care practice and future
      research.

PMID- 11845748
TI  - Communication skills: some problems in nursing education and practice.
AB  - This article is based on a literature review carried out as part of a study of
      communication skills training in pre-registration nursing education in England in
      2000. A systematic literature search was conducted and 200 articles were found
      that were relevant to the study. Definitional problems were found, with terms
      such as communication skills and interpersonal skills being used interchangeably.
      The term communications strategies is suggested to overcome these problems, as it
      reflects the logical organization of a number of different communication skills
      within a theoretical or empirical framework. Problems in current communication
      skills teaching and social barriers to using communication skills in practice are
      discussed. It is concluded that problems continue to exist in these areas and
      that an emphasis on both aspects is needed if patient and staff satisfaction is
      to be improved.

PMID- 11845749
TI  - Nurses' experience with vancomycin-resistant enterococci (VRE).
AB  - The emergence and spread of resistant organisms, in particular vancomycin
      resistant enterococci (VRE), is an issue facing all staff in acute hospitals.
      This study explored how nurses coped with the responsibility of halting further
      spread of this organism during an outbreak. VRE-positive patients were cohorted
      with nurses who cared for them in an endeavour to contain the spread of VRE. The
      majority of nurses found the situation extremely stressful because of the need to
      act as 'gatekeepers' responsible for educating and monitoring the practices of
      staff and visitors. The nurses reported that they felt they were inadequately
      supported, were blamed for the outbreak, and that they had an increased workload
      as they took on duties of other staff. The results reinforce the need for a
      multidisciplinary team approach to education and control of VRE, more support for
      nursing staff cohorted with VRE-positive patients, and stringent adherence to
      infection control measures by all hospital staff.

PMID- 11845750
TI  - The sensitivity and specificity of the Morse Fall Scale in an acute care setting.

PMID- 11845751
TI  - Barriers that delay children and young people who are dependent on mechanical
      ventilators from being discharged from hospital.
AB  - A qualitative study of user perspectives published previously by the author found
      that children and young people who are dependent on ventilators spend many months
      and in some cases years in hospital when they no longer had a medical need or
      wanted to be there. This second paper is drawn from the same qualitative study
      and reports on the barriers that the children and young people who are dependent
      on ventilators, and their parents, described as important factors in preventing
      their discharge from hospital. Six issues were identified as significant barriers
      that prevented the children and young people from being discharged. These were:
      the attitudes of professionals; the lack of joint commissioning and accounting
      responsibility; general poor management both within the health service and in
      collaborating with other services; complex social issues; housing problems; and a
      general lack of auditing and outcome measures. The generalizability of the
      findings is unknown. However, recommendations are made in relation to the need to
      establish joint commissioning and accounting responsibility for care and
      services, and to establish outcome measures to monitor the effectiveness and
      appropriateness of the care and services provided.

PMID- 11845752
TI  - 'Seeking': a key activity for new family carers of stroke survivors.
AB  - Stroke is one of the major causes of disability in the United Kingdom and
      considerable numbers of stroke survivors need help and support from family
      carers. The sudden and unexpected nature of stroke means that there is very
      little time for family members to prepare for a caring role. This paper draws on
      data from 37 interviews with 14 new carers of stroke survivors and highlights the
      uncertainty and lack of confidence that family members experience in adopting a
      caring role. During the initial period following the stroke carers engage in a
      number of different 'seeking' activities in order to try and ensure that they
      feel competent, confident and safe to provide care and that they understand the
      likely future demands they may face. Rather than being facilitated by staff,
      carers' efforts often go unnoticed or are overlooked, resulting in carers feeling
      that they are 'going it alone'. Staff need to be more aware of carers' 'seeking'
      behaviour and actively encourage the formation of partnerships with family
      members.

PMID- 11845753
TI  - The quality of nursing care as perceived by individuals with chronic illnesses:
      the magical touch of nursing.
AB  - Providing high quality nursing care is the vision of nursing. The literature has
      revealed gaps between the perspectives of patients and nurses regarding the
      quality of nursing care. The purpose of this study was to investigate how
      individuals with chronic illnesses perceive the quality of nursing care in order
      to enhance the quality of care. The participants were 11 Icelandic individuals,
      aged 39-80 years with various chronic illnesses. Phenomenology was the research
      approach and in-depth dialogues were used. Five themes emerged: nurses who
      provided high quality nursing care, the effects of high quality nursing care, the
      lack of good quality nursing care and its effects, ancillary factors, and the art
      of being a patient. Based on the findings I conclude that professional caring is
      the most important part of quality of care as perceived by individuals with
      chronic illnesses.

PMID- 11845754
TI  - Ovarian cancer patients: are their informational and emotional needs being met?
AB  - A study was undertaken to assess if the informational and emotional needs of
      ovarian cancer patients were being met according to their individual
      requirements. In the study, a gynaecology oncology specialist nurse provided
      hospital nursing support through individual care and a patients' support group. A
      questionnaire was completed by 24 patients using an integrated qualitative and
      quantitative data collection. This study showed that respondents evaluated
      positively the care provided in these two ways. Further research into the needs
      of gynaecological cancer patients should be undertaken.

PMID- 11845755
TI  - Spiritual needs as defined by Swedish nursing staff.
AB  - A study was undertaken to describe how Swedish nursing staff at six different
      units characterize spiritual needs in a broad context, including both religious
      and existential issues. Another aim was to study whether there are any special
      groups of patients for whom these needs are considered to be of utmost
      importance. A questionnaire comprising two open-ended questions (the focus of the
      study) and six background questions was mailed to 191 nurses. Data were obtained
      from 141 nurses who worked on the oncology, palliative, neurological,
      neurosurgery and psychiatric units or in nursing homes. Data from the open-ended
      questions were analysed using content analysis and classified into three
      categories: (i) (general) spiritual issues, (ii) religious issues, and (iii)
      existential issues. Sub-categories of the latter were (a) meaning, (b) freedom,
      (c) isolation and (d) death, i.e. the four central issues in existentialism as
      previously defined by existential philosophers. A majority of the nurses only had
      limited theoretical knowledge about definitions. Nevertheless, their suggestions
      for improved spiritual and existential support contained essential elements that
      could be allocated to the three main categories. They had some difficulty
      distinguishing between spiritual and psychosocial care. According to the nurses,
      special groups of interest for spiritual and existential support were severely
      ill, dying persons and immigrants who actively practiced their religion. We
      conclude that there is a willingness to pay attention to spiritual and
      existential needs, but nurses still have difficulty defining what such care
      should include. The study revealed that nursing staff needed, and also made
      inquiries about, more education in order to deepen their knowledge.

PMID- 11845756
TI  - Background pain in fibromyalgia patients affecting clinical examination of the
      skin.
AB  - The purpose of this study was to investigate the relationship between on-going
      pain and acute thermal pain in patients suffering from chronic pain. This
      experimental study in cold and heat sensitivity was performed in order to test
      the following hypothesis: that fibromyalgia patients scoring high in current
      background pain tolerate less experimental thermal pain in the skin than patients
      with low scores. Ethical aspects of the study are discussed. The level of
      tolerable experimental thermal stimuli was tested and compared between the 'low
      score' and the 'high-score' patients. Background pain seemed to affect the
      intensity of experimental cold pain. Clinical routine examinations and bodily
      care of the skin that might interfere with background pain in the fibromyalgia
      patients are discussed. Clinical practice should be carefully planned in order to
      assist fibromyalgia patients in understanding and coping with thermal conditions
      that might influence background pain.

PMID- 11845757
TI  - Diagnostic reasoning processes using patient simulation in different learning
      environments.
AB  - The purpose of the study was to explore the diagnostic reasoning process among
      nursing students with different learning environments. A case-study design was
      adopted. Twenty subjects were randomly drawn from the last year of a pre
      registration nursing programme in two institutions, 10 from a university and 10
      from a nursing school. They were asked to complete the Bigg's Study Process
      Questionnaire and identify the differential diagnosis for the three simulated
      scenarios. The results showed no significant difference in study approaches
      between the two groups. Two subjects from the university made an incorrect
      differential diagnosis, as did one from the nursing school. Subjects from the
      university showed a mix of horizontal (66.6%) and vertical reasoning patterns
      (33.4%), while those from the nursing school used horizontal (100%) reasoning
      patterns. The results indicated that all subjects from the nursing school adopted
      backward chaining strategies (horizontal) for decision-making, i.e. hypothesis
      driven. About a third of the subjects from the university adopted forward
      chaining strategies (vertical), i.e. data-driven. The study did not show any
      particular advantages from either of the two learning environments in terms of
      study approach. However, it highlighted the variations in decision strategies
      among students in the university setting.

PMID- 11845758
TI  - Learning intravenous cannulation: a comparison of the conventional method and the
      CathSim Intravenous Training System.
AB  - Intravenous cannulation is a nursing procedure carried out in some clinical units
      that may induce trauma and discomfort. Nurses should be well prepared before
      practising the procedure with clients. Conventionally, a plastic arm was used for
      practice but, with innovative developments in technology, a computer program
      called the CathSim Intravenous Training System (CathSim ITS) is available for
      this purpose. This study was conducted to compare the effectiveness of learning
      using a plastic arm with the CathSim ITS. Twenty-eight nurses were divided into
      two groups and randomly assigned to the two different methods: plastic arm
      (control group) or CathSim ITS (experimental group). Both groups were provided
      with 1 hour of theory input and 2 hours of nursing laboratory work. When the
      nurses felt ready to practise on clients, their performances were assessed by
      researchers with an intravenous cannulation qualification using a validated
      checklist. Prior to the assessment, trait and state anxiety levels were measured
      using the State-Trait Anxiety Inventory (Hong Kong Chinese adaptation) to check
      whether anxiety would affect the performance. Following the assessment, a semi
      structured interview was conducted to reveal my knowledge acquired through using
      the selected method. Both the control and CathSim ITS groups demonstrated a high
      success rate, scoring 100% and 92.86%, respectively, with their first client. The
      semi-structured interviews revealed that the CathSim ITS group appreciated
      several features of their assigned method. However, there is room for further
      development.

PMID- 11845759
TI  - A multicentre comparative evaluation: washable pants with an integral pad for
      light incontinence.
AB  - The Continence Product Evaluation Network (CPE network) is funded by the Medical
      Devices Agency (MDA) of the Department of Health, to undertake comparative
      evaluations of continence products. There are a wide variety of continence
      products on the UK market and very little information is available to aid product
      selection. The aim of this study was to evaluate washable pants with integral
      pads for women with light incontinence. A randomized multiple cross-over design
      was used. Seventy-two women tested each of the 10 products that were available on
      the UK market at the time of the evaluation. Both subjective and objective
      outcome measures were used to evaluate the products. Products performed similarly
      in terms of leakage but there were statistically significant differences in other
      performance aspects, e.g. fit and discreteness. This study should be valuable in
      enabling purchasers, carers and users to make informed decisions when purchasing
      products.

PMID- 11845760
TI  - An action research project to evaluate the clinical practice facilitator role for
      junior nurses in an acute hospital setting.
AB  - It has been well documented that newly qualified nurses require support in
      developing confidence and professional competence. Although preceptorship models
      have gone some way in addressing this need, innovative and flexible models of
      facilitation and development are also required to respond to local demands. In
      the project reported here a number of supernumerary clinical practice
      facilitators (CPFs) were appointed to support both healthcare assistants and
      newly qualified registered nurses to enhance their competence and clinical
      skills. It was anticipated that they might also encourage awareness of other
      professional issues, such as evidence-based practice, as well as having a
      positive influence on the clinical learning environment and staff morale. This
      article describes how an action research approach was used to establish the CPF
      role in a variety of clinical areas across a large inner-city National Health
      Service Trust. It outlines the evaluation undertaken and the further contribution
      that such roles could provide.

PMID- 11845761
TI  - The practice of community caregivers in a home-based HIV/AIDS project in South
      Africa.
AB  - The aim of this study was to describe the practice of community caregivers in a
      home-based AIDS care project at seven sites in South Africa. The community
      caregivers felt positive about the contribution they made, but found it difficult
      to cope with the poverty and complexity of problems they were faced with. They
      visited each client an average of five times per month, and their care usually
      involved counselling and informing, symptom control, psychosocial support and
      welfare assistance. The caregivers worked in close collaboration with the South
      African Hospice Association and clinic staff, and each site developed a work
      pattern suitable to its resources.

PMID- 11845762
TI  - Quo vadis? Advanced practice nursing or advanced nursing practice?

PMID- 11845763
TI  - Continence nursing: a whole person approach.
AB  - Urinary incontinence has significant medical, social, psychologic, and economic
      implications. Continence management requires a sensitive, comprehensive, and
      holistic approach that accounts for the many facets of this distressing and life
      altering condition. Assessment of urinary incontinence includes a focused
      physical examination, comprehensive history, and accounting for factors that can
      impact continence, such as cognition, functional ability, and impact on quality
      of life. Behavioral therapy for incontinence includes diet modification,
      toileting programs, bladder retraining, and pelvic muscle re-education.
      Biofeedback and electrical stimulation are treatment modalities that help clients
      to identify, recruit, and strengthen pelvic floor muscles and improve treatment
      outcomes. Other approaches include medications and devices, such as a pessary.

PMID- 11845764
TI  - The tapestry of hospice.
AB  - Members of the hospice team weave a tapestry of care with patients and families.
      Relief of suffering--physical, emotional, and spiritual--is the goal of hospice
      care. Nurses' contribution to that care is central but often seemingly unnoticed.
      Their contribution to the tapestry constitutes the subtle threads of the
      background upon which the tapestry evolves. Nurses' work is often viewed
      simplistically, and the complexity of simple tasks is hidden. Work examples of
      nurses in hospice are discussed, and the previously unseen yet central parts of
      nurses' work are highlighted.

PMID- 11845765
TI  - Formerly incarcerated women create healthy lives through participatory action
      research.
AB  - The specific purpose of the participatory action research study was to facilitate
      formerly incarcerated women who participate in Welcome Home Ministries (WHM) to
      develop their own plans and specific strategies, and to take action to build
      their own healthy futures. The research had a duel purpose of joint generation of
      knowledge and intervention relative to women's capacity building. The research
      intervention was the creation, implementation, and follow-up of a future search
      conference. The outcomes, conclusions, and implications for practice are
      discussed.

PMID- 11845766
TI  - Teaching on the front lines: using the Internet and problem-based learning to
      enhance classroom teaching.
AB  - Working on the front lines in health care at the bedsides, in the primary and
      specialty care offices and in the community with patients; and in health care
      education, teaching graduate and undergraduate students, is more challenging
      today than ever before. Shifts in reimbursement from fee for service to a managed
      care model, increasingly informed consumers, and increasingly complex health
      problems create a tension that often leaves the advanced practice nurse (APN)
      managing conflicting human and business interests. Nurse educators must prepare
      providers to function in that world. Using Problem-Based Learning (PBL) to
      provide APN students with experiences that will supply them with rehearsal will
      better prepare them to function in today's primary care environment. Providing
      PBL using the Internet is the next logical step and may insure that this type of
      experience is more widely available to students.

PMID- 11845767
TI  - Nurse practitioners and traditional healers: an alliance of mutual respect in the
      art and science of health practices.
AB  - The indigenous people of Hawaii have had difficulty adapting to the Western diet
      and stressful lifestyle of today's mixed cultural and economic development. This
      has left a health toll of high rates of diabetes, hypertension,
      hypercholesterolemia, cardiovascular problems, asthma, and obesity. To promote a
      healthy lifestyle and promote the U.S. Department of Health and Human Services
      (DHHS) goal of 100% access to health care and 0% disparity (no one will be denied
      health care), nurse practitioner/traditional Hawaiian healing clinics have been
      placed in community settings, which are known to community people and comfortable
      to access. These clinics provide health care to uninsured and underinsured people
      in an atmosphere that assures respect for the culture and the health needs. This
      pilot study examines the perceptions of 30 residents of Hawaii and the type of
      provider sought. Seventy-five percent of the respondents were generally satisfied
      with the health care received from both Hawaiian and Western care providers. Back
      and neck problems and injuries were associated with the use of Hawaiian therapies
      and appeared to reflect chronic conditions. Western health care is sought for
      predominantly acute conditions (infections, allergies, and upper respiratory
      conditions) and for diabetes and hypertension.

PMID- 11845769
TI  - The four S's of wound management: staples, sutures, Steri-Strips, and sticky
      stuff.
AB  - Wound management is a daily occurrence in many practices. A short summary of
      current research in wound management is documented. Wound assessment guidelines
      are discussed. Included are evaluation of the patient's tetanus status, wound
      complexity and age, decisions as to the use of antibiotics, and closure methods.
      Follow-up care, patient education, and special considerations are also discussed.
      Billing information is considered. The objective of this article is that reader
      be able to: 1. Identify several closure options for commonly seen wounds 2.
      Identify selection criteria for use of Steri-Strips, sutures, and surgical glue
      in closing wounds and lacerations 3. Identify criteria indicating the need for
      antibiotics and the most common causative microbial agents associated with wounds
      4. Identify over-the-counter (OTC) surgical glues and their popular uses 5.
      Evaluate immunization status and recommend appropriate treatment for wound
      prophylaxis.

PMID- 11845770
TI  - Advanced practice nursing: on the front lines.

PMID- 11845768
TI  - Outcomes of training nurses to conduct breast and cervical cancer screening of
      Native American women.
AB  - Native WEB (Women Enjoying the Benefit) is a unique training program for nurses
      employed by the Indian Health Service (IHS), tribal clinics, and other clinics
      with large, underserved populations. It teaches nurses breast and cervix cancer
      screening techniques and trains them to administer and maintain high-quality
      screening programs that include patient outreach, education, and training. We
      review American Indian (AI)/Alaska Native (AN) women's need for screening
      services, identify some of the obstacles to screening, and present our evaluation
      of the Native WEB's impact on clinics, nurses, and patients. Findings show that
      Native WEB training is associated with increased screening activity at all three
      levels.

PMID- 11845771
TI  - Hospice and Palliative Nursing Study Guide introduced.

PMID- 11845772
TI  - HHNA participates in City of Hope educational project.

PMID- 11845773
TI  - [Modern pharmacotherapy of patients with chronic cardiac insufficiency]].

PMID- 11845774
TI  - [Peptide regulation of aging].
AB  - The paper shows a new concept of the mechanisms responsible for aging with
      emphasis on regulatory peptides. The concept opens basically new approaches to
      preventing premature aging, to prolonging the individual's active life, and
      eliminating pathological states and processes associated with age-specific
      changes. The regulatory peptides described in the paper are now regarded as new
      generation therapeutical and preventive agents that can produce a naturally
      target corrective action on the diseased organ and tissue without adverse side
      effects.

PMID- 11845775
TI  - [Status of immune system organs after exposure to intense physical loads and
      during the recovery period].
AB  - The course of reparative processes in the organs of the immune system has been
      found to be related to the individual response of animals to exercise and their
      status after its termination. Three groups of rats differently adapted to
      exercise were identified. In Group 1 animals, a drastic cessation of exercise
      leads to a prompt recovery of the histological pattern of organs (thymus, spleen)
      under study 2 weeks later. In Group 2 animals show reparative processes which run
      slowly and the structure of the thymus and spleen even 4 weeks after exercise.
      While in Group 3 animals, cessation of exercise inhibits immune functions and
      reduces the body's responsiveness.

PMID- 11845776
TI  - [Receptor mechanisms for realizing the effect of glucocorticoid hormones in
      traumatic and hemorrhagic shock].
AB  - Blood corticosterone concentrations showed a 2-fold increase in traumatic and
      hemorrhagic shock. Following 4 hours of injury, the rat hepatic cytasol density
      of glucocorticoidal receptor II and III decreased to 76 and 67% of the level of
      intact animals, respectively. There were changes in the physicochemical
      properties of glucocorticoidal receptors: an increase in Ka and a decrease in Kd
      of the hormone-receptor complexes. A direct relation was found of the
      glucocorticoid-binding capacity of receptors II to blood pressure (BP) in shock.
      The most marked suppression of receptors II was noted in hemorrhagic shock, which
      seems to be due to more profound systemic hemodynamic changes and low BP in this
      type of shock. There was a concurrent reduction in the density of receptors I and
      II up to the certain decrease in the levels of receptors II, then was an increase
      in receptor III binding of [3H]-corticosterone. With the low density of receptors
      II and with the high concentration of corticosterone, this appears to be aimed at
      preserving the glucocorticoid-dependent activation of the cell genetic apparatus.
      Dysfunctions found in the glucocorticoidal receptors are a cause of the
      development of relative glucocorticoid deficiency in shock.

PMID- 11845777
TI  - [Sex hormones and behavioral reactions].
AB  - The paper provides a comparative analysis of the effects of imbalance of gonadal
      hormones on behavioral processes in rats of both sex. Learning was assesses in
      active and passive avoidance paradigms, behavior was evaluated in the "open
      field" test. Hemigonadectomy in male rats or hemiovariectomy in female rats was
      found to fail to modify the dynamics of acquisition and reproduction of active
      avoidance and passive reactions as compared to the controls, but to affect the
      pattern of animal behavior in the "open field" test. Castration of rats of both
      sex impaired the acquisition and retention of active avoidance performance.
      Excess of testosterone in male rats significantly inhibited the ability of the
      animals to form an active avoidance response. Excessive estradiol levels in
      female rats accelerated the acquisition of active avoidance performance and
      greatly attenuated extinction of this performance. Gonadal hormonal treatment did
      not alter the reproducibility of passive avoidance performance. The lack of
      estrogens resulted in amnesia of passive avoidance performance while that of
      androgens failed to destroy passive avoidance performance. Excessive estradiol in
      female rats or its lack in male rats significantly modified the pattern of animal
      behavior in the "open field" test. The absence of estrogens or their excess did
      not affect the behavior of rats with exception of individual components.

PMID- 11845778
TI  - [B. V Petrovsky's scientific school at the turn of two centuries].
AB  - The paper shows how Academician B. V. Petrovsky's scientific school has been set
      up and how it has developed. Three stages of its development are identified: 1)
      the establishment and formation of the school on the basis of the department, the
      development of large areas of surgery (cardiovascular, thoracic, and esophageal
      surgeries) in 1951 to 1963; 2) the development of the school within the research
      institute-department system, the setting up of its branches, specialized services
      in the country, organizational and methodological management of its related
      research institutes in 1963 to 1989; and 3) the present period marked by the
      design and introduction of high technologies, the development of topical research
      problems (transplantation of the heart and liver, including related, miniinvasive
      surgery, computer-aided monitoring, telemedicine, as well as staff training).
      Four world's priorities of the school are noted. They included as follows:
      diaphragmatic plasty on a vascular pedicle for various abnormalities; the world's
      richest experience in surgically treating gunshot wounds of the large blood
      vessels during military actions; discovery of the physiological mechanisms of the
      function and properties of the valve-aorta complex of the human aortic root; the
      design and successful clinical application of nitinolic memory prostheses to
      endoprosthesis. The paper predicts how surgery will develop in the 21st century.

PMID- 11845779
TI  - [Pancreatic hormone amylin and integrity of the gastric mucosa].
AB  - The paper presents experimental findings of some possible mechanisms of
      protective antiulcerous action of amyline. Amyline is the second beta-cell
      pancreatic hormone, which has been just recently discovered. The authors have
      studied the effects of amyline on gastric secretion, mast cell functions,
      mesenteric lymphatic microvascular contractility, i.e. on individual aggressive
      and protective factors of the gastric mucosa. Amyline has been found to inhibit
      basal acid gastric secretion and the secretion stimulated by vagal irritation.
      The peptide reduces the secretory activities of mast cells. Amyline given to
      animals increases the heparin saturation index of mast cells and decreases the
      degranulation index. Amyline-induced stabilization of mast cells appears to
      followed by the decreased release of histamine and other damaging substances. The
      stimulating effect of amyline on the contractile activity of mesenteric lymphatic
      vessels was recorded in rats. Amyline increases both the frequency and amplitude
      of their contractions. The increased lymph flow that is closely associated with
      microcirculation promotes the maintenance of tissue homeostasis. Therefore, the
      protective antiulcerous properties of amyline reduce the action of aggressive
      agents on the gastric mucosa and stimulate protective ones.

PMID- 11845780
TI  - [Bacterial IgA1-protease: production, properties and prospects for use].
AB  - Some pathogenic bacteria have been demonstrated to secrete specific IgA1
      proteases, the enzymes cleaving the molecules of the first subclass of human
      immunoglobulin (IgA1) in the single point from the hinge with the formation of
      Fab- and Fc-fragments. Cleavage generally deprives immunoglobulins having defense
      properties and the enzymes are considered as pathogenic factors. How to determine
      the activity, purification, and the promises of use of IgA-proteases is
      described. Whether inactivated meningococcal IgA1-protease as a vaccine against
      any of the five (A, B, C, Y, W135) serotypes of pathogenic meningococci is
      discussed.

PMID- 11845781
TI  - [Intensive forms of education and student health].

PMID- 11845782
TI  - [Pathogenetic basis for using interferon-beta preparations in treating multiple
      sclerosis].

PMID- 11845783
TI  - [Outstanding biochemist S. E. Severin (on the 100th anniversary of his birth)].

PMID- 11845784
TI  - [Hemoaggregatology and blood surgery].
AB  - Hemaggregatology was formed as a new trend in blood science in the second part of
      the 20th century. Hemaggregatology underwent several stages in its development.
      This gave rise to a theory of the systematic regulation of blood aggregation and
      a new trend in surgery, such as blood gravitation surgery. Subsequently all
      instrumental corrective techniques for blood aggregation were integrated into a
      special part surgery--blood surgery.

PMID- 11845785
TI  - Proceedings of the Xth International Symposium on Purines and Pyrimidines in Man.
      May 14-19, 2000. Tel Aviv, Israel.

PMID- 11845787
TI  - Computational chemistry in the 1950s.

PMID- 11845786
TI  - Structural biology of T-cell costimulatory proteins: New insights, more
      surprises.

PMID- 11845788
TI  - [Esthetics of face; development of a scale for the measurement of facial
      esthetics].
AB  - The aim of this study was to develop a measurement scale to quantify facial
      appearance. Four series of 36 facial photographs, boys and girls at two ages,
      were judged twice by three different panels by means of ratio estimation.
      Pearson's correlation coefficients were calculated to determine intra- and inter
      observer agreement (median r = .78 and .71 respectively) as well as inter-panel
      agreement (median r = .84). Cronbach's alpha coefficients were established as a
      measure for the homogeneity within each jury panel (median alpha = .906). The
      results showed that reproducibility of the ratings as well as agreement between
      different observers were sufficient. Therefore, a mean overall score for each
      photograph could be calculated. Finally, for each group a metric scale was
      composed, consisting of five photographs with their scores.

PMID- 11845789
TI  - [Dentists' opinions of their dental education; results of a survey of dentists
      who studied in Amsterdam between the years 1982-1990].
AB  - Four hundred and fifty dental graduates from the Free University (VU), the
      University of Amsterdam (UvA) or the Academic Center for Dentistry Amsterdam
      (ACTA) between 1982 and 1990 were asked by questionnaire to give their opinion
      about the undergraduate dental training they received. Most respondents felt that
      their undergraduate education prepared them reasonably well for general practice.
      Yet imperfections in the education were noticed. These imperfections show
      resemblance to conclusions from similar surveys in other countries.

PMID- 11845790
TI  - [Etiology of the fear of dentistry].
AB  - In the present study, 192 extremely anxious dental patients were asked for the
      factors which may have influenced their dental anxiety. The results showed that a
      traumatic dental experience, personality and professional behaviour of the
      dentist, persons in the direct environment, and psychological background all
      played an important role. Almost all extremely anxious dental patients had more
      than one negative experience with the dental treatment. Most patients acquired
      their anxiety at an early age.

PMID- 11845791
TI  - [Substance-related diseases--tobacco smoking and alcohol consumption].

PMID- 11845794
TI  - Geron settles WARF.

PMID- 11845793
TI  - Endoscopic fluorescence detection of low and high grade dysplasia in Barrett's
      oesophagus using systemic or local 5-aminolaevulinic acid sensitization.

PMID- 11845792
TI  - Evaluation of mediastinal lymphadenopathy with endoscopic US-guided fine-needle
      aspiration biopsy.

PMID- 11845795
TI  - Avigen AAV trial continues.

PMID- 11845797
TI  - [Report on the 18th Scandinavian Medical History Congress, Copenhagen, June 13-16
      2001].

PMID- 11845798
TI  - [The thyroid gland in Anothomia Mundini (1316)].
AB  - Andreas Vesalius described the human thyroid lobes very distinctly in his De
      humani corporis fabrica in 1543 calling them glandulae laryngis. Before him
      Leonardo da Vinci had depicted the human thyroid gland in his anatomical
      drawings. The first publication which could be called a textbook of human
      anatomy, because it was used as the basis for cathedral teaching in human anatomy
      for about two centuries, was the Anothomia of Mundinus Liucius, Mondino
      de'Liuzzi, published in 1316. In the chapter on the blood vessels of the neck he
      describes two glands, which he calls amigdalae, situated under the longitudinal
      muscles and below the larynx. Their function should be 1) to wet the trachea; 2)
      to fill the grove below the larynx because the neck was broader above due to the
      large larynx but much slender below because of the narrower trachea. And 3): they
      should function as a shield for the deep arteries and veins. Later anatomists at
      the beginning of the 15th and the 16th century, like Achillini, Massa and Zerbus,
      all used the text of Mundinus but obviously they tried to locate the glands of
      Mundinus to the tonsils apparently only because he used the denomination
      amigdalae. Berengario da Carpi, however, who was a much experienced anatomist,
      published a large treatise Commentaria super Anothomia Mundini in which he
      confirms the location of the glands of Mundini below the larynx. Obviously the
      two glands in the neck Mundinus mentions are the two thyroid lobes. According to
      his description they cannot be the tonsils because 1) of their location below the
      larynx, and 2) their function of adequating the appearance of the neck and 3)
      shielding, at least to some extent, the deep vessels in the neck. Before Mundini
      there is no similar description of the anatomy of the human neck in the
      literature, so what he describes must he based upon his own experience.
      Furthermore, he did the autopsies himself and did not use the assistance of a
      prosector as the professors after him used to do.

PMID- 11845796
TI  - ImClone BLA is declined.

PMID- 11845799
TI  - [Frans Johan Rabbe: the father of the history of medicine in Finland].
AB  - F. J. Rabbe is the one who can be regarded as the real father of the history of
      medicine in Finland and who also was a member of the Medical Board. It was Rabbe
      who already in 1843 wrote the first paper on the history of different types of
      hospitals such as the leper hospitals, the county hospitals, the hospitals for
      veneral diseases as well as the military and psychiatric hospitals which
      gradually had been established in Finland since the middle of the 14th century.
      Rabbe also collected and published all the medical laws and decrees issued in
      Finland between 1683 and 1845. Later Rabbe published a lot of different
      statistical material on medical conditions in Finland as well as biographies of
      medical doctors. He also made a comprehensive work on the history of medicine in
      Finland, about 3000 handwritten pages, which unfortunately only has been saved as
      a manuscript and has not been published(5).

PMID- 11845800
TI  - Long-term total parenteral nutrition with growth, development, and positive
      nitrogen balance. 1968.

PMID- 11845801
TI  - Controlling faecal incontinence (including constipation and bowel dysfunction).
AB  - Spina bifida may affect faecal continence in many ways.  An understanding of the
      issues can assist general practitioners in supporting their patients through the
      process of learning to effectively management specialist centres.

PMID- 11845802
TI  - [Role of delta opioid receptors and their ligands in the development of adaptive
      heart protection against arrhythmogenesis].
AB  - It has been found that stimulation of delta-1 opioid receptors by intravenous
      administration of DPDPE (0.5 mg/kg) decreases the incidence of ischemic and
      reperfusion-induced arrhythmias and also increases myocardial tolerance to the
      arrhythmogenic action of epinephrine in rats. Pretreatment with a selective delta
      2 agonist, DSLET, had no antiarrhythmic effect. The inhibition of the enzymatic
      breakdown of endogenous enkephalins by intravenous administration of acetorphan
      decreased the incidence of epinephrine-induced arrhythmias. Pretreatment with a
      selective delta opioid receptor antagonist, ICI-174.868, completely abolished
      this antiarrhythmic effect. Adaptation of rats to repeated immobilization stress
      during 12 days increased myocardial tolerance to the arrhythmogenic action of
      coronary artery occlusion (10 min) and reperfusion (10 min). Pretreatment with a
      selective delta opioid receptor antagonist, TIPP(Psy), did not abolish the
      antiarrhythmic effect of adaptation to immobilization stress. It seems that
      endogenous agonists of delta opioid receptors are not involved in the
      antiarrhythmic effect resulting from adaptation to stress.

PMID- 11845803
TI  - Continuous 12-lead ST-segment monitoring improves identification of low-risk
      patients with chest pain and a worse in-hospital outcome.
AB  - BACKGROUND: Various strategies have been proposed to improve diagnosis and triage
      of patients with chest pain at low risk, but uncertainty still exists on the
      optimal combination of diagnostic tools that should be used in this subset of
      patients. HYPOTHESIS: The aim of this study was to evaluate the incremental
      benefit of continuous 12-lead ST-segment monitoring over that provided by
      conventional diagnostic tools in patients with chest pain. METHODS: Of 232
      consecutive patients referred because of chest pain, 52 were classified as low
      risk according to the Agency for Health Care Policy and Research unstable angina
      guidelines and observed for 12 h with serial cardiac enzymes and
      electrocardiograms (ECG) (every 3 h). All patients also underwent both
      echocardiography at entry and continuous 12-lead ST-segment monitoring during the
      observation period. RESULTS: During a mean hospital stay of 3.7 days (range 1-14
      days), a benign outcome was observed in 37 patients (71%), whereas 15 patients
      (29%) had major cardiac events or recurrence of chest pain of ischemic origin.
      Addition of ST-segment monitoring findings to baseline clinical data as well as
      to serial enzymes and ECG features added significant incremental prognostic value
      (p < 0.001). Multivariate analysis showed reproduction of pain by chest pressure
      (p < 0.05) and presence of ST-segment changes (> or = 0.1 mV) during 12-lead ST
      segment monitoring (p < 0.001) as independent predictors of a benign or
      unfavorable outcome. CONCLUSIONS: In low-risk patients with chest pain,
      continuous 12-lead ST-segment monitoring provides significant incremental
      diagnostic and prognostic information to currently used clinical, enzymatic, and
      ECG data, and is helpful in identifying the subset of patients with a worse in
      hospital outcome.

PMID- 11845804
TI  - The use of serum tTG-ab assay in patients on gluten-free diet as a measure of
      dietetic compliance.

PMID- 11845805
TI  - Esophageal adenocarcinoma arising from Barrett's metaplasia has regional
      variations in the west.

PMID- 11845806
TI  - Barrett's esophagus and neoplasia: data from the Bayreuth Barrett's archive.

PMID- 11845807
TI  - Serine protease inhibitors and F-actin redistribution.

PMID- 11845808
TI  - Immunomodulatory drugs in Crohn's disease patients with hepatitis B or C virus
      infection.

PMID- 11845810
TI  - Complications from radiofrequency ablation of liver metastases.
AB  - The objective of this study is to evaluate complications from radiofrequency
      ablation of liver metastases. Eighty-one liver tumors in 38 consecutive patients
      were treated with radiofrequency ablation. All patients had one to six metastases
      treated in a single session. Eight patients underwent radiofrequency ablation
      intraoperatively after laparotomy and the remaining 30 patients were treated
      percutaneously with CT or ultrasound guidance. A total of 43 radiofrequency
      ablation procedures were studied. There was one (2%) mortality related to a
      hepatic abscess development 8 days after the procedure. One patient (3%) required
      a blood transfusion. Three patients (8%) developed severe upper abdominal or
      pleuritic chest pain that persisted several days after the procedure. We conclude
      that radiofrequency ablation of liver metastases is associated with a low rate of
      serious complications (two of 38; 5%). Complications requiring treatment usually
      develop several days after the procedure.

PMID- 11845809
TI  - Improved breast cytology results with near patient FNA diagnosis.
AB  - OBJECTIVE: To examine the impact of a cytopathologist using near patient fine
      needle aspiration diagnosis (NPFD) for breast diagnosis. STUDY DESIGN: The
      cytology results of all palpable solid breast lesions undergoing fine needle
      aspiration (FNA) during a two-year period were prospectively audited and
      categorized as definitely benign or malignant (definite), probably benign,
      indeterminate or suspicious (indefinite) or unsatisfactory. The final diagnosis
      (benign or malignant) was determined from a review of patients' charts and a
      survey of patients' family physicians. Aspirates were performed by surgical
      staffand reported either later (non-NPFD) or by NPFD. RESULTS: Of 720 FNAs, 230
      were by NPFD and 490 by non-NPFD. NPFD was associated with a significantly
      greater proportion of definite reports (91.9% versus 82.4%). NPFD of discrete
      breast lumps was associated with higher specificity (89.1% versus 67.5%) and a
      lower unsatisfactory rate (9.4% versus 19.6%) than non-NPFD. NPFD did not improve
      the unsatisfactory rate of FNAs from diffuse breast thickenings. CONCLUSION: FNA
      by a dedicated specialist and immediate reporting should be an integral part of a
      breast diagnostic service.

PMID- 11845811
TI  - The sharp end of medical practice: the use of acupuncture in obstetrics and
      gynaecology.

PMID- 11845812
TI  - Definition of a type of abnormal vaginal flora that is distinct from bacterial
      vaginosis: aerobic vaginitis.
AB  - OBJECTIVE: To define an entity of abnormal vaginal flora: aerobic vaginitis.
      DESIGN: Observational study. SETTING: University Hospital Gasthuisberg, Leuven,
      Belgium. SAMPLE: 631 women attending for routine prenatal care or attending
      vaginitis clinic. METHODS: Samples were taken for fresh wet mount microscopy of
      vaginal fluid, vaginal cultures and measurement of lactate, succinate and
      cytokine levels in vaginal fluid. Smears deficient in lactobacilli and positive
      for clue cells were considered to indicate a diagnosis of bacterial vaginosis.
      Aerobic vaginitis was diagnosed if smears were deficient in lactobacilli,
      positive for cocci or coarse bacilli, positive for parabasal epithelial cells,
      and/or positive for vaginal leucocytes (plus their granular aspect). RESULTS:
      Genital complaints include red inflammation, yellow discharge, vaginal
      dyspareunia. Group B streptococci, escherichia coli, staphylococcus aureus and
      trichomonas vaginalis are frequently cultured. Vaginal lactate concentration is
      severely depressed in women with aerobic vaginitis, as in bacterial vaginosis,
      but vaginal succinate is not produced. Also in contrast to bacterial vaginosis,
      aerobic vaginitis produces a host immune response that leads to high production
      of interleukin-6, interleukin-1-beta and leukaemia inhibitory factor in the
      vaginal fluid. CONCLUSION: Aerobic vaginitis is associated with aerobic micro
      organisms, mainly group B streptococci and E. coli. Its characteristics are
      different from those of bacterial vaginosis and elicit an important host
      response. The most severe form of aerobic vaginitis equals desquamative
      inflammatory vaginitis. In theory, aerobic vaginitis may be a better candidate
      than bacterial vaginosis as the cause of pregnancy complications, such as
      ascending chorioamnionitis, preterm rupture of the membranes and preterm
      delivery.

PMID- 11845813
TI  - Prevention of postpartum stress incontinence in primigravidae with increased
      bladder neck mobility: a randomised controlled trial of antenatal pelvic floor
      exercises.
AB  - OBJECTIVE: To test whether supervised pelvic floor exercises antenatally will
      reduce the incidence of postpartum stress incontinence in at-risk primigravidae
      with bladder neck mobility, ultrasonically proven. DESIGN: Single blind,
      randomised controlled trial. SETTING: Antenatal clinic in a UK NHS Trust
      Hospital. SAMPLE: Two hundred and sixty-eight primigravidae attending an
      antenatal clinic at approximately 20 weeks of gestation with bladder neck
      mobility, on standardised valsalva, of 5 mm or more linear movement. The median
      age was 28, ranging from 16 to 47 years. INTERVENTION: Patients randomised to
      supervised pelvic floor exercises (n = 139) attended a physiotherapist at monthly
      intervals from 20 weeks until delivery. The exercises comprised three repetitions
      of eight contractions each held for six seconds, with two minutes rest between
      repetitions. These were repeated twice daily. At 34 weeks of gestation the number
      of contractions per repetition was increased to 12. Both the untreated control
      group and the study group received verbal advice on pelvic floor exercises from
      their midwives antenatally. MAIN OUTCOME MEASURES: Subjective reporting of stress
      incontinence at three months postpartum. Pelvic floor strength, using
      perineometry, and bladder neck mobility measured by perineal ultrasound. RESULTS:
      Of the 268 women enrolled, information on the main outcome variable was available
      for 110 in the control group and 120 in the study group. Fewer women in the
      supervised pelvic floor exercise group reported postpartum stress incontinence,
      19.2% compared with 32.7% in the control group (RR 0.59 [0.37-0.92]). There was
      no change in bladder neck mobility and no difference in pelvic floor strength
      between groups after exercise, although all those developing postpartum stress
      incontinence had significantly poorer perineometry scores than those who were
      continent. CONCLUSIONS: The findings suggest that antenatal supervised pelvic
      floor exercises are effective in reducing the risk of postpartum stress
      incontinence in primigravidae with bladder neck mobility.

PMID- 11845814
TI  - Muscle strength and tibolone: a randomised, double-blind, placebo-controlled
      trial.
AB  - OBJECTIVE: To investigate the effects of tibolone, a tissue-specific compound
      with a mixed (estrogenic, progestogenic and androgenic) hormonal profile, on
      skeletal muscle strength in a group of healthy postmenopausal women. DESIGN:
      Randomised, parallel group, double-blind, placebo-controlled, single-centre trial
      conducted between August 1997 and July 1999. PARTICIPANTS: Eighty-five healthy
      women, between one and 15 years postmenopausal, (mean [SD] age, 54.2 [4.7] years)
      recruited from local paper advertisements. Participants were randomly assigned to
      2.5 mg tibolone or to identically appearing placebo pills daily for 12 months,
      taken orally in the morning. METHODS: Both maximal handgrip strength,
      representing upper body strength, and maximal quadriceps strength, representing
      lower body strength, were measured isometrically. MAIN OUTCOME MEASURES:
      Treatment effect estimates (between group differences) in handgrip strength and
      isometric knee extension at last visit. RESULTS: Tibolone significantly (P =
      0.04) increased handgrip strength compared with placebo (difference 0.99 kg, [95%
      CI 0.1-1.9]). No significant treatment effect (P = 0.61) was observed in
      isometric knee extension strength. Isometric strength adjusted for body mass
      index resulted in a trend favouring tibolone (P = 0.06). Individual trend
      analysis showed a significant difference in rate of change throughout the year
      (6.8% [95% CI 2.1-10.7]) favouring tibolone. CONCLUSIONS: Administration of
      tibolone increased handgrip strength in postmenopausal women compared with
      placebo. A trend indicating a positive effect in isometric knee extension
      strength adjusted for body mass index was observed. Tibolone seems to mitigate
      the menopause-related decline in muscle strength.

PMID- 11845815
TI  - High incidence of cervical human papillomavirus infection in women during their
      first sexual relationship.
AB  - The prevalence of cervical human papillomavirus increases with increasing numbers
      of sexual partners, leaving the impression that this infection is acquired only
      as a result of high risk sexual behaviour. Using longitudinal data from 242 women
      who had only had one sexual partner, we found that the risk of acquiring cervical
      human papillomavirus infection was 46% (95% CI 28-64) at three years after first
      intercourse and that the median time from first intercourse to first detection of
      human papillomavirus was only three months.

PMID- 11845816
TI  - Abstracts of the 14th International Congress of Cytology. May 27-31, 2001.
      Amsterdam, the Netherlands.

PMID- 11845817
TI  - From farm to table to brain: foodborne pathogen infection and the potential role
      of the neuro-immune-endocrine system in neurotoxic sequelae.
AB  - The American diet is among the safest in the world; however, diseases transmitted
      by foodborne pathogens (FBPs) still pose a public health hazard. FBPs are the
      second most frequent cause of all infectious illnesses in the United States.
      Numerous anecdotal and clinical reports have demonstrated that central nervous
      system inflammation, infection, and adverse neurological effects occur as
      complications of foodborne gastroenteritis. Only a few well-controlled clinical
      or experimental studies, however, have investigated the neuropathogenesis. The
      full nature and extent of neurological involvement in foodborne illness is
      therefore unclear. To our knowledge, this review and commentary is the first
      effort to comprehensively discuss the issue of FBP induced neurotoxicity. We
      suggest that much of this information supports the role of a theoretical model,
      the neuro-immune-endocrine system, in organizing and helping to explain the
      complex pathogenesis of FBP neurotoxicity.

PMID- 11845818
TI  - Development of a PCR-compatible enrichment medium for Yersinia enterocolitica:
      amplification precision and dynamic detection range during cultivation.
AB  - A Yersinia PCR-Compatible Enrichment (YPCE) medium was developed, which removes
      the necessity for sample pretreatment before PCR-based detection of Yersinia
      enterocolitica. The medium was designed through a sequence of independent
      screening and factorial design experiments to study the PCR inhibition and growth
      characteristics of medium components. The compatibility of the YPCE medium was
      evaluated using real-time PCR. The real-time PCR assay, based on the fluorescent
      double-stranded DNA binding dye SYBR green, generated approximately a 4-log
      linear range of amplification and in the range of 10(5)-10(8) (CFU/ml), the
      coefficient of variation <5%. When a background flora was present at
      concentrations > or = 10(6) (CFU/ml), the DNA amplification was influenced and a
      change in the log-linear slope leading to a lower amplification efficiency was
      observed. To study the dynamic detection range and relative amplification
      precision during enrichment. Y. enterocolitica and background flora were
      inoculated at various concentrations. It was possible to detect inoculation
      concentrations of 10(1) (CFU/ml) Y. enterocolitica in the presence of at least an
      inoculation concentration of 10(3) (CFU/ml) of an undefined background flora and
      the optimal conditions for sample withdrawal was in the range of 9 to 18 h
      enrichment. The YPCE medium can, especially for swab samples, form part of a
      simple analysis procedure allowing high throughput PCR.

PMID- 11845819
TI  - Detection and quantification of ochratoxin A and deoxynivalenol in barley grains
      by GC-MS and electronic nose.
AB  - Mycotoxin contamination of cereal grains can be detected and quantified using
      complex extraction procedures and analytical techniques. Normally, the grain
      odour, i.e. the presence of non-grain volatile metabolites, is used for quality
      classification of grain. We have investigated the possibility of using fungal
      volatile metabolites as indicators of mycotoxins in grain. Ten barley samples
      with normal odour, and 30 with some kind of off-odour were selected from Swedish
      granaries. The samples were evaluated with regard to moisture content, fungal
      contamination, ergosterol content, and levels of ochratoxin A (OA) and
      deoxynivalenol (DON). Volatile compounds were also analysed using both an
      electronic nose and gas chromatography combined with mass spectrometry (GC-MS).
      Samples with normal odour had no detectable ochratoxin A and average DON contents
      of 16 microg kg(-1) (range 0-80), while samples with off-odour had average OA
      contents of 76 microg kg(-1) (range 0-934) and DON contents of 69 microg kg(-1)
      (range 0-857). Data were evaluated by multivariate data analysis using projection
      methods such as principal component analysis (PCA) and partial least squares
      (PLS). The results show that it was possible to classify the OA level as below or
      above the maximum limit of 5 microg kg(-1) cereal grain established by the
      Swedish National Food Administration, and that the DON level could be estimated
      using PLS. Samples with OA levels below 5 microg kg(-1) had higher concentration
      of aldehydes (nonanal, 2-hexenal) and alcohols (1-penten-3-ol, 1-octanol).
      Samples with OA levels above 5 microg kg(-1) had higher concentrations of ketones
      (2-hexanone, 3-octanone). The GC-MS system predicted OA concentrations with a
      higher accuracy than the electronic nose, since the GC-MS misclassified only 3 of
      37 samples and the electronic nose 7 of 37 samples. No correlation was found
      between odour and OA level, as samples with pronounced or strong off-odours had
      OA levels both below and above 5 microg kg(-1). We were able to predict DON
      levels in the naturally contaminated barley samples using the volatile compounds
      detected and quantified by either GC-MS or the electronic nose. Pentane,
      methylpyrazine, 3-pentanone, 3-octene-2-ol and isooctylacetate showed a positive
      correlation with DON, while ethylhexanol, pentadecane, toluene, 1-octanol, 1
      nonanol, and 1-heptanol showed a negative correlation with DON. The root mean
      square error of estimation values for prediction of DON based on GC-MS and
      electronic nose data were 16 and 25 microg kg(-1), respectively.

PMID- 11845820
TI  - Two antioxidative lactobacilli strains as promising probiotics.
AB  - Two antioxidative strains tentatively identified as Lactobacillus fermentum, E-3
      and E-18, were isolated from intestinal microflora of a healthy child. Survival
      time of these strains in the presence of reactive oxygen species (ROS), like
      hydrogen peroxide, superoxide anions and hydroxyl radicals, was significantly
      increased compared with a non-antioxidative strain, and also was quite similar to
      a highly ROS resistant strain of Salmonella typhimurium. E-3 and E-8 contain a
      remarkable level of glutathione, express Mn-SOD, which is important for the
      prevention of lipid peroxidation, and secrete hydrogen peroxide. Their
      significant antimicrobial activity combined with antioxidative properties may
      serve as defensive principles in the intestinal microbial ecosystem and overcome
      exo- and endogenous oxidative stress.

PMID- 11845821
TI  - The influence of temperature, salt and pH on the inhibitory effect of reuterin on
      Escherichia coli.
AB  - The inhibitory effect of reuterin on Escherichia coli K12 was investigated at
      different conditions of temperature (10-30 degrees C), pH (4.5-6.5), and NaCl
      (0.5-3% (w/v)). The maximum specific growth rate as a function of the different
      environmental conditions was modelled with a polynomial model. At increasing
      temperatures, there was an increasing effect of reuterin, whereas neither pH nor
      salt showed interactions with the effect of reuterin. The model was validated
      against new experimental data and proved to perform satisfactorily based on the
      bias and accuracy factors.

PMID- 11845823
TI  - High-pressure inactivation of Bacillus cereus spores in the presence of argon.
AB  - We investigated the high-pressure inactivation of Bacillus cereus spores in water
      containing argon. At the pressure of 600 MPa, addition of argon accelerated the
      inactivation of spores at 20 degrees C, but had no effect on the inactivation at
      40 degrees C. The influence of added argon on inactivation of the spores was
      marked under conditions with a strong 'water ordering' effect. The pressure
      resistance of B. cereus spores was thus shown to be affected by 'water ordering'.

PMID- 11845822
TI  - Survival and growth of enterotoxin-positive and enterotoxin-negative Clostridium
      perfringens in laboratory media.
AB  - The survival and growth characteristics of enterotoxin-positive and enterotoxin
      negative Clostridium perfringens were compared. Spores of C. perfringens were
      heated and incubated in laboratory media to simulate the cooking and inadequate
      storage of cooked food. In our experiment, enterotoxin-positive and enterotoxin
      negative spores were heated and incubated individually and it was found that
      spores of enterotoxin-positive strains were more heat-resistant than spores of
      the enterotoxin-negative strains. In another experiment, cocktails of enterotoxin
      positive and enterotoxin-negative spores were heated and incubated. At the time
      of inoculation, the ratio of enterotoxin-positive spores to enterotoxin-negative
      spores was about 1:100. In the case of high-temperature heat treatment, the
      number of enterotoxin-negative spores decreased to below that of enterotoxin
      positive spores after heating, and enterotoxin-positive strains grew to high
      levels during incubation. In the case of low-temperature heat treatment, the
      number of enterotoxin-negative spores remained almost unchanged after heating and
      enterotoxin-positive strains did not grow to high CFU levels during incubation.

PMID- 11845824
TI  - [Heat transfer analysis of liquid cooling garment used for extravehicular
      activity].
AB  - Brief description was given about the construction and function of the LCG
      (liquid cooling garment) used for EVA (extravehicular activity). The heat
      convection was analyzed between ventilating gas and LCG, the heat and mass
      transfer process was analyzed too, then a heat and mass transfer mathematical
      model of LCG was developed. Thermal physiological experimental study with human
      body wearing LVCG (liquid cooling and ventilation garment) used for EVA was
      carried out to verify this mathematical model. This study provided a basis for
      the design of liquid-cooling and ventilation system for the space suit.

PMID- 11845825
TI  - [Bone adaptation and response to mechanical stress in bone].
AB  - To review the progresses in the research of bone adaptation and its mechanisms.
      The Wolff's law represented early theory of bone adaptation, but the Frost's
      mechanostat theory developed in 1960s might be the more appropriate theory.
      Several studies showed that the bone cells including osteoblasts, osteocytes and
      bone lining cells are the mechanosensitive cells in bone tissue. Forces acting on
      the bone cells include compressive-tensile stress and shear stress. The shear
      stress is the main force which can be sensed by the bone cells. The effect of
      shear stress on bone cells is closely related to the basic structure of the bone,
      i.e., osteon. The main responses of bone cells to stress are changes of secretion
      of prostaglandins and nitric oxide.

PMID- 11845826
TI  - [Influence of gravity change on EGF-induced signal transduction].
AB  - With the development of aerospace technology, biological effects induced by
      alteration of gravitation are drawing more and more attention. Among them the
      influence of alteration of gravitation on cytokine-induced signal transduction
      has been well studied recently. Epidermal growth factor (EGF)-induced signal
      transduction can activate increase of cell proliferation in most cell types, so
      it is always a hotspot in these years. Among the early effects evoked by EGF are
      receptor clustering, cell rounding, and early gene expression. After the study
      about the induction of EGF on human A431 cell line, it was observed that EGF
      induced c-fos and c-jun expression decreased in microgravity. This was caused by
      alteration of the EGF receptor and protein kinase C-mediated signal transduction
      pathways. Meanwhile the key component of cytoskeleton, the actin microfilament
      system, was found to be linked to the EGF-induced signal transduction cascades
      either. So it seems reasonable to suggest that the cytoskeleton constitutes the
      gravity-sensitive cell component.

PMID- 11845828
TI  - [Important bio-thermal physical problems and latest advancement in laser cell
      engineering].
AB  - The recently emerging technique of laser microsurgery (optical tweezers, optical
      scissors, etc.) is providing a new precise, sterile method for the cell
      engineering practices such as introduction of external gene into an object cell,
      cell-fusion, and trapping or transportation of microscopic objects (cells or
      chromosomes etc.). The thermal effects thus induced usually proved to be critical
      factors for successful operation of this method. In order to meet the requirement
      for the rapid development in this territory, some important bio-thermal physical
      problems and the corresponding research subjects in this area were
      comprehensively summarized. Difficulties and critical issues were discussed. The
      latest advancement of the laser cell engineering was also described. This review
      is attempted to bridge up the gap between bioengineering and thermal science
      fields and then to enhance the rapid progress of laser microsurgery.

PMID- 11845827
TI  - [The progress on +Gz stress-induced injuries of the cardiac structure and
      function and their mechanisms].
AB  - The heart is the dynamic pump of the circulation. To some extent, high +Gz
      acceleration exposure can result in injuries on cardiac ultrastructure,
      metabolism and function. Specifically, repeated +Gz exposures can produce harmful
      effects on aviators, as reported by French and American researchers. However, the
      mechanisms of injuries on heart under high +Gz stress have not been studied
      systematically till now; nor have some protective measures been adopted. In this
      article, acute and chronic +Gz stress induced injuries on cardiac structure and
      function in animals and detrimental effects on the hearts of pilots are reviewed.
      Moreover, the related mechanisms are also explained basing on stress injury,
      oxidative stress and genetic regulation.

PMID- 11845829
TI  - Radiation payout: the US government settles out of court over experiments on
      cancer patients.

PMID- 11845830
TI  - Focus: is it ethical for surgeons to cut patients open and sew them up without
      doing anything?

PMID- 11845831
TI  - Determination of the physical and chemical properties, biokinetics, and dose
      coefficients of uranium compounds handled during nuclear fuel fabrication in
      France.
AB  - The introduction of new ICRP recommendations, especially the new Human
      Respiratory Tract Model (HRTM) in ICRP Publication 66 led us to focus on some
      specific parameters related to industrial uranium aerosols collected between 1990
      and 1999 at French nuclear fuel fabrication facilities operated by COGEMA, FBFC,
      and the CEA. Among these parameters, the activity median aerodynamic diameter
      (AMAD), specific surface area (SSA), and parameters describing absorption to
      blood f(r), s(r) and s(s) defined in ICRP Publication 66 were identified as the
      most relevant influencing dose assessment. This study reviewed the data for 25
      pure and impure uranium compounds. The average value of AMAD obtained was 5.7
      microm (range 1.1-8.5 microm), which strongly supports the choice of 5 microm as
      the default value of AMAD for occupational exposures. The SSA varied between 0.4
      and 18.3 m2 g(-1). For most materials, values of the absorption parameters f(r),
      s(r), and s(s) derived from the in vitro experiments were generally consistent
      with those derived from the in vivo experiments. Using average values for each
      pure compound allowed us to classify UO2 and U3O8 as Type S, mixed oxides, UF4,
      UO3 and ADU as Type M, and UO4 as Type F based on the ICRP Publication 71
      criteria. Dose coefficients were also calculated for each pure compound, and
      average values for each type of pure compound were compared with those derived
      using default values. Finally, the lung retention kinetics and urinary excretion
      rates for inhaled U03 were compared using material-specific and default
      absorption parameters, in order to give a practical example of the application of
      this study.

PMID- 11845832
TI  - Chernobyl accident: retrospective and prospective estimates of external dose of
      the population of Ukraine.
AB  - Following the Chernobyl accident many activities were conducted in Ukraine in
      order to define the radiological impact. Considered here are gamma spectrometric
      analyses of soil-depth-profile samples taken in the years 1988-1999, gamma
      spectrometric measurements of radionuclide concentration in soil samples taken in
      1986, and measurements of external gamma-exposure rate in air. These data are
      analyzed in this paper to derive a "reference" radionuclide composition and an
      attenuation function for the time-dependent rate of external gamma exposure that
      changes due to the migration of radiocesium into the soil column. An attenuation
      function for cesium is derived that consists of two exponential functions with
      half lives of 1.5 and 50 y. The dependencies of attenuation on direction and
      distance from the Chernobyl Nuclear Power Plant are also demonstrated. On the
      basis of these analyses the average individual and collective external gamma
      doses for the population of Ukraine are derived for 1986, 1986-2000, and 1986
      2055. For the 1.4 million persons living in rural areas with 137Cs contamination
      of >37 kBq m(-2), the collective effective dose from external exposure is
      estimated to be 7,500 person-Sv by the end of 2000. A critical group of 22,500
      persons who received individual doses of >20 mSv is identified for consideration
      of increased social and medical attention.

PMID- 11845833
TI  - Reconstruction and analysis of 137Cs fallout deposition patterns in the Marshall
      Islands.
AB  - Estimates of 137Cs deposition caused by fallout originating from nuclear weapons
      testing in the Marshall Islands have been estimated for several locations in the
      Marshall Islands. These retrospective estimates are based primarily on historical
      exposure rate and gummed film measurements. The methods used to reconstruct these
      deposition estimates are similar to those used in the National Cancer Institute
      study for reconstructing 131I deposition from the Nevada Test Site. Reconstructed
      cumulative deposition estimates are validated against contemporary measurements
      of 137Cs concentration in soil with account taken for estimated global fallout
      contributions. These validations show that the overall geometric bias in
      predicted-to-observed (P:O) ratios is 1.0 (indicating excellent agreement). The
      5th to 95th percentile range of this distribution is 0.35-2.95. The P:O ratios
      for estimates using historical gummed film measurements tend to slightly
      overpredict more than estimates using exposure rate measurements. The deposition
      estimate methods, supported by the agreement between estimates and measurements,
      suggest that these methods can be used with confidence for other weapons testing
      fallout radionuclides.

PMID- 11845834
TI  - Skeletal dosimetry via NMR microscopy: investigations of sample reproducibility
      and signal source.
AB  - Nuclear magnetic resonance microscopy has been used for several years as a means
      of quantifying the 3D microarchitecture of the cancellous regions of the
      skeleton. These studies were originally undertaken for the purpose of developing
      non-invasive techniques for the early detection of osteoporosis and other bone
      structural changes. Recently, nuclear magnetic resonance microscopy has also been
      used to acquire this same 3D data for the purpose of both (1) generating chord
      length data across bone trabeculae and marrow cavities and (2) generating 3D
      images for direct coupling to Monte Carlo radiation transport codes. In both
      cases, one is interested in the reproducibility of the dosimetric data obtained
      from nuclear magnetic resonance microscopy. In the first of two studies, a
      trabecular bone sample from the femoral head of a 51-y-old male cadaver was
      subjected to repeated image acquisition, image processing, image coupling, and
      radiation transport simulations. The resulting absorbed fractions at high
      electron energies (4 MeV) were shown to vary less than 4% among four different
      imaging sessions of the same sample. In a separate study, two femoral head
      samples were imaged under differing conditions of the NMR signal source. In the
      first case, the samples were imaged with intact marrow. These samples were then
      subjected to marrow digestion and immersed in Gd-doped water, which then filled
      the marrow cavities. Energy-dependent absorbed fraction profiles for both the
      marrow-intact and marrow-free samples showed essentially equivalent results.
      These studies thus provide encouragement that skeletal dosimetry models of
      improved patient specificity can be achieved via NMR microscopy in vivo.

PMID- 11845835
TI  - In situ calibration and evaluation of the accuracy of a waste water monitoring
      system.
AB  - A new method to estimate the reliability of a waste water monitoring system was
      developed and substantiated. To estimate the reliability means (1) to verify the
      representativeness of the sample fed into the monitoring system, and (2) to
      calibrate the detectors of the monitoring system. To verify the
      representativeness, test water spiked with 32P was prepared in a storage tank,
      and the monitoring system was operated. For all of the experiments, the
      radioactivity concentrations of the water fed into the monitoring system agreed
      well with those of the water in the storage tank at 725 +/- 45 s after the start
      of the sampling pump. Therefore, the representativeness was verified. Calibration
      was carried out with active water in the storage tank and in a specially designed
      calibration tank. The efficiency of a plastic scintillation detector (PSD), one
      of the detectors used in the monitoring system, for 32P was determined to be 4.91
      +/- 0.10%. Using the calibration tank significantly reduced the cost and labor
      for calibration. In addition, calibration with natural potassium (40K) proved to
      be effective for periodic checks of the detector.

PMID- 11845836
TI  - What is the meaning of threshold in laser injury experiments? Implications for
      human exposure limits.
AB  - The derivations of human exposure limits for laser radiation rely heavily upon
      experimental ocular injury studies. The limits are derived by committees of
      ophthalmic experts through a review of all available threshold data and an
      understanding of mechanisms of laser/tissue interaction. A major point of
      discussion in this derivation process relates to the level of uncertainty of the
      threshold of injury. An indication of the level of uncertainty relates to the
      slope of the transformed dose-response curve, or the "probit plot" of the data.
      The most cited point on the probit plot is the exposure that represents a 50%
      probability of injury: the ED-50. This value is frequently referred to as the
      "threshold," even though some experimental damage points exist below this
      "threshold." An analysis of any number of example data sets reveals that the
      slope in most experiments cannot be explained by biological variation alone. The
      optical, thermophysical, and biological factors influencing the probit plot are
      critically analyzed to provide guidance for deriving exposure limits. By
      theoretically modeling an experiment, small errors in focus are shown to produce
      a substantial change in the ED-50 and the slope of the probit plot.

PMID- 11845837
TI  - New in-vivo calibration phantoms and their performance.
AB  - New in-vivo calibration phantoms (anthropometric phantoms) were developed to meet
      the needs for Japanese standard phantoms. Two important characteristics of these
      phantoms were that (1) they were designed using Japanese body size survey data,
      and (2) they were designed so that they can be adapted to various positions or
      geometries. The performance of these phantoms was tested with respect to body
      size, activity distribution along the axis, and counting efficiency. The actual
      dimensions of the anthropometric phantoms were compared with the survey data.
      Most items (31 of 47) indicated good agreement between the actual values and the
      survey data for the adult anthropometric phantom. The activity distribution for
      the anthropometric phantoms was compared with that for block phantoms that
      simulate a uniform activity distribution. The anthropometric phantoms have some
      gaps in their joints. The measurement results, however, indicated that these gaps
      did not significantly affect the overall accuracy of the measurements.
      Differences in counting efficiency between the block phantoms and the
      anthropometric phantoms for the same age were no more than 6%.

PMID- 11845838
TI  - An assessment of gas emanation hazard using a geographic information system and
      geostatistics.
AB  - This paper describes the use of geostatistical analysis and GIS techniques to
      assess gas emanation hazards. The Mt. Vulsini volcanic district was selected for
      this study because of the wide range of natural phenomena locally present that
      affect gas migration in the near surface. In addition, soil gas samples that were
      collected in this area should allow for a calibration between the generated
      risk/hazard models and the measured distribution of toxic gas species at surface.
      The approach used during this study consisted of three general stages. First data
      were digitally organized into thematic layers, then software functions in the GIS
      program "ArcView" were used to compare and correlate these various layers, and
      then finally the produced "potential-risk" map was compared with radon soil gas
      data in order to validate the model and/or to select zones for further, more
      detailed soil gas investigations.

PMID- 11845839
TI  - Radioactivity appearing at landfills in household trash of nuclear medicine
      patients: much ado about nothing?
AB  - The U.S. NRC in 1997 removed its arbitrary 1.11 GBq (30 mCi) rule, which had been
      in existence for almost 50 y, and now many more patients receiving radionuclide
      therapy in nuclear medicine can be treated as outpatients. However, another
      problem has the potential to limit the short-lived reality of outpatient
      treatment unless nuclear medicine practitioners and the health physics community
      gets involved. Radioactive articles in the household trash of nuclear medicine
      patients are appearing at solid waste landfills that have installed radiation
      monitors to prevent the entry of any detectable radioactivity, and alarms are
      going off around the country. These monitors are set to alarm at extremely low
      activity levels. Some states may actually hold licensees responsible if a
      patient's radioactive household trash is discovered in a solid waste stream; this
      is another major reason [along with continued use of the 1.11 GBq (30 mCi) rule]
      why many licensees are still not releasing their radionuclide therapy patients.
      This is in spite of the fact that the radioactivity contained in released nuclear
      medicine therapy patients, let alone the much lower activity level contained in
      their potentially radioactive household wastes, poses a minimal hazard to the
      public health and safety or to the environment. Currently, there are no
      regulations governing the disposal of low-activity, rapidly-decaying radioactive
      materials found in the household trash of nuclear medicine patients, the
      performance of landfill radiation monitors, or the necessity of spectrometry
      equipment. Resources are, therefore, being unnecessarily expended by regulators
      and licensees in responding to radiation monitor alarms that are caused by these
      unregulated short-lived materials that may be mixed with municipal trash.
      Recommendations are presented that would have the effect of modifying the
      existing landfill regulations and practices so as to allow the immediate disposal
      of such wastes.

PMID- 11845841
TI  - Medical aspects of radiofrequency radiation overexposure.
AB  - Despite seemingly widespread concerns about radiofrequency radiation overexposure
      to the general population, there is very little in the medical literature that
      addresses this issue. This article is written by a consensus-forming body
      composed of physicians, biologists, engineers, and physical scientists. It
      addresses those aspects of radiofrequency radiation exposure that are pertinent
      to clinical medicine. It is intended to provide basic information on
      radiofrequency radiation injuries to be helpful to physicians should they ever be
      presented with a patient who was overexposed to radiofrequency radiation. Salient
      features of radiofrequency radiation physics, radiofrequency radiation injuries,
      and national safety standards are discussed. A synopsis of the signs and symptoms
      of radiofrequency radiation overexposure and a statement concerning the role of a
      physician are also included. This Note is intended to update practitioners on the
      best available information on radiofrequency radiation exposure management and
      the results of recent national and international standard setting activities.

PMID- 11845840
TI  - On being understood: clarity and jargon in radiation protection.
AB  - While much of the language used to express the concepts of radiation protection
      works effectively, there are many ill-chosen names and phrases and much jargon
      that permeate our professional speech and writing. From the oxymoron "internal
      exposure" to the "snarl word" "decay," there is much room for improvement. This
      essay identifies many of the problems and suggests solutions. We examine the
      kinds of confusions that can result from using familiar words with unfamiliar
      meanings and the need for neology. We offer insights into specific and
      unambiguous naming of physical quantities and explore the seemingly unlimited
      kinds of "dose." We disaggregate exposure from irradiation following intakes, and
      unmask units like "gram rad per microcurie hour." We call for a definition of
      radiation weighting factor that doesn't result in a violation of the law of
      conservation of energy. We examine the subtleties of distinguishing between
      radiation and radioactive materials. Some words, such as "exposure," have
      multiple meanings, while at other times there are different words or phrases with
      the same meaning, such as "critical level" and "decision level" or "detection
      level" and "minimum detectable amount." Sometimes phrases are used whose meaning
      is unclear or not agreed upon, such as "lower limit of detection." Sometimes
      there are words that are simply not apt, such as "disintegration" applied to the
      emission of a subatomic particle from a nucleus.

PMID- 11845842
TI  - Absorbed fraction sensitivity to changes in size of the ICRP nose model.
AB  - The Human Respiratory Tract Model of ICRP Publication 66 is used for calculations
      of dose in the extrathorathic (ET1) airways. Scaling for age and body size is
      included in determining the mass of the target tissue (basal cells) in ET1 but is
      not included in deriving the absorbed fraction for particulate radiation. For
      dose calculations, it has been assumed that all absorbed fractions for
      particulate radiation published in ICRP Publication 66 are independent of age and
      body size. Therefore, these absorbed fractions are applied to calculate specific
      effective energy values not only for the Reference Worker but also for non-adults
      with noses of different sizes. In this note changes to the size of the cylinder
      model of the anterior nose in ICRP 66 are made by varying the surface area, the
      cylinder radius, and the thickness of tissue beyond the target region (basal
      cell). The energy deposition (absorbed fractions) in the target region (basal
      cells) is calculated using the MCNP4B (Monte Carlo) code to study the effects of
      these changes on the predicted absorbed fractions within the cylinder model.

PMID- 11845843
TI  - An evaluation and comparison of compliance inspection outcomes data for radiation
      protection programs in Maine and Texas.
AB  - The coding system used by the State of Texas Department of Health Bureau of
      Radiation Control to categorize regulatory violations resulting from compliance
      inspections was applied to the results of similar activities performed by the
      State of Maine Radiation Control Program for licensees of radioactive materials
      in calendar year 1999. The coded results from the Maine inspections (n = 37) were
      then summarized and compared to the data from Texas inspection activities for
      similar radiation licenses (n = 1,350). Despite significant differences in
      program size, age, and geographic proximity, the list of most commonly issued
      violations was almost identical. Other program outcome analogies were also noted,
      such as similar violation frequency distributions and similar identified root
      causes of non-compliance. These comparisons mark the first step towards the
      possible creation of a generalizable list of common items of non-compliance,
      which could serve to greatly enhance radiation safety preventive education and
      training programs. The utility of the Texas coding system as the basis for
      interstate program comparisons is also demonstrated, since the system is based
      upon categories of non-compliance rather than locally-unique regulatory codes or
      citations.

PMID- 11845844
TI  - The ethics of operating radon health spas.

PMID- 11845845
TI  - Our responsibility for improving the care of elderly cardiothoracic surgical
      patients.

PMID- 11845846
TI  - Effects of antireflux procedures on respiratory symptoms.
AB  - BACKGROUND: Antireflux surgery can reduce respiratory symptoms associated with
      gastroesophageal reflux. However, there is a paucity of data on the durability of
      this benefit. To evaluate the long-term effects of antireflux surgery on
      respiratory complaints associated with gastroesophageal reflux, we reviewed our
      experience. METHODS: Retrospective review of 2,123 antireflux procedures
      completed between 1986 and 1998 identified 65 patients (3.1%) with associated
      respiratory symptoms. There were 32 men and 33 women, ranging in age from 20 to
      80 years (median 59 years). Respiratory symptoms included wheezing in 43
      patients, sputum production in 37, cough in 30, choking episodes in 24, and
      hoarseness in 17. Preoperative medication use included steroids in 23 patients
      and bronchodilators in 18. RESULTS: Antireflux operations included the uncut
      Collis-Nissen fundoplication in 29 patients, Belsy Mark IV repair in 13, open
      Nissen fundoplication in 13, and laparoscopic Nissen fundoplication in 10.
      Perioperative complications occurred in 19 patients who underwent open procedures
      and in none who had laparoscopic procedures. There was one death in the open
      operation group and none in the laparoscopic group. Median follow-up was 65
      months (range 1 to 174 months) and was complete in 62 patients (96.9%).
      Improvement in respiratory symptoms (83%) and reduction in-respiratory medication
      use (78%) were significant as compared to a calculated 33% placebo-effect
      improvement (p < 0.05). CONCLUSIONS: Antireflux operations significantly reduce
      respiratory complaints associated with gastroesophageal reflux. This benefit
      appears to be long term.

PMID- 11845847
TI  - Natural history of pure ground-glass opacity after long-term follow-up of more
      than 2 years.
AB  - BACKGROUND: Pure ground-glass opacity (PGGO) is a new entity that has been
      clearly defined on high-resolution computed tomography (CT) during the last half
      decade. It is important to investigate the natural history of PGGO through long
      term observation for the management of this new entity. METHODS: We investigated
      19 patients with PGGO(s) defined on high-resolution computed tomography and
      retained as PGGO for more than 2 years. The PGGOs of 11 patients were detected at
      annual mass screening by low-radiation-dose CT (low-dose CT), 7 at follow-up CT
      after cancer resection, and 1 incidentally on CT. After long-term observation, 10
      of 19 patients underwent operation and 9 are currently being followed-up with CT.
      Their growth characteristics and histologic findings are reported. RESULTS: The
      median follow-up period was 32 months, ranging from 24 to 124 months. The sizes
      of PGGOs at the time of discovery were 4 to 18 mm in largest diameter (average
      8.6 mm). During follow-up, the size of PGGO showed no change in 8 patients,
      increased slightly (up to 5 mm) in 6 patients, and increased by more than 5 mm in
      5 patients. Ten patients had limited resection (segmentectomy or wide wedge
      resection) with negative surgical margin by intraoperative lavage cytology of the
      resection margin of the lung. Of them, 5 patients had adenocarcinoma, 3 pulmonary
      lymphoproliferative disorder, and 1 each atypical adenomatous hyperplasia and
      focal fibrosis. There was no clear tendency between the degree of size change and
      histology. In all but 1 of 9 patients with follow-up only, the PGGOs showed
      either no change or only a slight increase within 5 mm in largest diameter.
      CONCLUSIONS: These data suggest that some PGGOs will never progress to clinical
      disease and would be included in the category of overdiagnosis bias. However, a
      prior history of lung cancer should significantly raise the index of suspicion,
      as 4 of 5 proven cancer cases in this small series fell into that category.
      Because of the difficulties of preoperative and intraoperative histodiagnosis of
      PGGO, minimally invasive surgery may be appropriate from the viewpoints of both
      diagnosis and curability.

PMID- 11845848
TI  - Can FDG-PET reduce the need for mediastinoscopy in potentially resectable
      nonsmall cell lung cancer?
AB  - BACKGROUND: Few fluoro-deoxy-glucose (FDG)-positron emission tomography (PET)
      nonsmall cell lung cancer (NSCLC) trials have had sufficient patients to
      adequately evaluate PET for mediastinal staging. We question whether once PET is
      performed, is mediastinoscopy necessary? METHODS: We performed a 5-year
      retrospective analysis of operable patients with known or suspicious NSCLC.
      Standard PET techniques were used. Inclusion criteria were (1) surgical
      mediastinal nodal sampling by mediastinoscopy within 31 days of the PET and (2)
      definitive diagnosis. RESULTS: There were 237 patients who met the evaluation
      criteria; ninety-nine patients with NSCLC and 138 with suspicious lesions (137
      men and 100 women; aged 20 to 88 years). The PETs were performed from 0 to 29
      days before mediastinoscopy (median, 7 days). The standardized uptake value for
      the primary lesion was 0 to 24.6 (7.9+/-5.0). Nine primary lesions had no FDG
      uptake (1 benign, 8 NSCLCs). Seventy-one patients (31%) had mediastinal PET
      positive disease, and 44 patients (19%) had histologic positive mediastinal
      disease; N2 41 patients (17%) and N3 9 patients (4%). In 6 patients (3%), the
      initial frozen sections were negative, but PET positivity encouraged further
      biopsies that were positive for cancer. The PET sensitivity was 82%, specificity
      82%, accuracy 82%, negative predictive value 95%, and positive predictive value
      was 51%. All primary lesions with a standardized uptake value less than 2.5 and a
      negative mediastinal PET were negative histologically (n = 29). Logistic
      regression analysis resulted in 100% specificity for PET in this group.
      CONCLUSIONS: In NSCLC PET may reduce the necessity for mediastinoscopy when the
      primary lesion standardized uptake value is less than 2.5 and the mediastinum is
      PET negative. Accepting this approach in our patient population, the need for
      mediastinoscopy would have been reduced by 12%.

PMID- 11845849
TI  - Detection of estrogen receptor by immunohistochemistry in pulmonary
      adenocarcinoma.
AB  - BACKGROUND: The distinction between primary adenocarcinoma and metastatic breast
      carcinoma in the lung is important for therapeutic purposes. There is a good deal
      of morphologic overlap between primary pulmonary adenocarcinoma and breast
      carcinoma metastatic in the lung. Many diagnosticians rely upon the presence of
      estrogen receptor (ER) in tumors of the lung in women in order to make a
      pathologic diagnosis of metastatic breast carcinoma. There are conflicting data
      in the literature regarding the presence of ER in lung carcinomas. In this study,
      we examined primary lung adenocarcinomas with monoclonal antibodies to two
      different clones to ER (clone 6F11 and clone 1D5), and progesterone receptor by
      the immunoperoxidase method in order to ascertain if ER is detectable in primary
      lung adenocarcinomas. METHODS: Twenty-five resected solitary pulmonary
      nonmucinous bronchioalveolar carcinomas (15 female, 10 male) and 20 resected
      solitary pulmonary adenocarcinomas of no special type (12F, 8 mol/L) were studied
      by the immunohistochemical method using heat-induced epitope retrieval.
      Immunostaining was semiquantitated, and positive results included nuclear
      staining for ER and progesterone receptor. All of these tumors were documented as
      primary pulmonary adenocarcinomas clinically and pathologically. RESULTS: Nuclear
      ER was seen only with the 6F11 clone, in 56% of the bronchioalveolar type and 80%
      of the no special type. No nuclear ER was seen in carcinomas utilizing the 1D5
      clone. There was no progesterone receptor detectable in carcinomas. CONCLUSIONS:
      Estrogen receptor is present in the majority of lung adenocarcinomas, and
      detection of ER in lung adenocarcinomas is dependent upon the antibody clone that
      is used. Epitope recognition may account for the differences in immunoreactivity
      between these two antibodies, although a cross-reactive antibody reaction cannot
      be completely excluded. Further study is warranted to discern the nature of the
      6F11 clone immunoreactivity with nuclei of lung adenocarcinomas. The clinical
      significance and ramifications of ER in pulmonary adenocarcinomas remain unknown.
      Caution should be exercised by clinicians and pathologists in accepting a
      diagnosis of metastatic breast carcinoma in lung based on the presence of ER
      detected by clone 6F11.

PMID- 11845850
TI  - Role of fiberscopic transbronchial needle aspiration in the staging of N2 disease
      due to non-small cell lung cancer.
AB  - BACKGROUND: Transbronchoscopic needle aspiration (TBNA) can offer a unique
      opportunity to identify surgically unresectable lung cancer and to avoid surgical
      mediastinal exploration in many patients with mediastinal lymph node extension of
      the tumor. The aim of this study was to assess the yield of TBNA performed with
      either histology or cytology needles in mediastinal staging of N2 disease due to
      non-small cell lung cancer (NSCLC). METHODS: Retrospective chart review was
      carried out on 194 TBNA procedures performed between January 1997 and September
      2000 at a single institution. Inclusion criteria were pathologic evidence of
      NSCLC; contrast enhancement computed tomography scan of the chest suggesting N2
      disease; and negative bronchoscopic examination for possible neoplastic lesions
      at the site of RESULTS: Overall sensitivity and diagnostic accuracy were 71% and
      73%, respectively, with no significant differences between 19-gauge and 22-gauge
      cytology needles. Procedures performed for right paratracheal and subcarinal
      lymph node stations had a significantly higher yield than those for the left
      paratracheal station. CONCLUSIONS: TBNA mediastinal staging, performed during the
      initial diagnostic evaluation of NSCLC, can spare costs and risks of more
      invasive procedures in patients with inoperable tumors, in patients who are not
      candidates for operation because of coexistent significant comorbidities, and in
      patients with N2 disease.

PMID- 11845851
TI  - Malignant minor pleural effusion detected on thoracotomy for patients with non
      small cell lung cancer: is tumor resection beneficial for prognosis?
AB  - BACKGROUND: This study attempts to clarify the benefit of surgery for non-small
      cell lung cancer (NSCLC) with malignant minor pleural effusion that is detected
      at thoracotomy. METHODS: Records of surgical patients with NSCLC were reviewed,
      with a definition of minor pleural effusion as less than 300 mL. The patients
      were divided into three groups as follows: (1) group C consisted of patients who
      underwent grossly complete resection; group I, patients with incomplete tumor
      resection; and group E, patients who underwent exploratory thoracotomy only.
      RESULTS: There were 196 patients who had minor pleural effusion; of these, 96
      (46%) underwent an examination to define the malignancy status of pleural
      effusion after surgery. In 43 patients (45%), the effusion was found to be
      malignant. The median survival time and 5-year survival rate, respectively, were
      13 months and 9% for group C (n = 11); 34 months and 10% for group I (n = 14; p =
      0.3); and 17 months and 0% for group E (n = 18; p = 0.8). CONCLUSIONS: Tumor
      resection is not beneficial for the survival of patients with NSCLC who have a
      minor malignant pleural effusion.

PMID- 11845852
TI  - "True" parahiatal hernia: a rare entity radiologic presentation and clinical
      management.
AB  - BACKGROUND: True parahiatal diaphragmatic hernias are rare entities that are
      sparsely accounted for in the literature. The current report is intended to
      depict the clinical profile and assess the feasibility of laparoscopic repair of
      parahiatal hernias. METHODS: We conducted a retrospective review of all patients
      diagnosed and treated for parahiatal hernias. Clinical presentation and
      radiological assessment, as well as operative findings and repair, are discussed.
      RESULTS: Of the 917 laparoscopic hiatal hernia repairs, 2 (0.2%) patients were
      identified with a parahiatal hernia. The presenting symptoms and preoperative
      testing were similar to those with more common paraesophageal hernias.
      Laparoscopic repair was successful in repairing the diaphragmatic defect and
      alleviating symptoms up to 4 years postoperatively. CONCLUSIONS: Parahiatal
      hernias of the diaphragm appear to be rare primary diaphragmatic defects. The
      clinical presentation of parahiatal hernias is often indistinguishable from the
      more common paraesophageal pathology. Laparoscopic repair of this rare entity can
      be safely and successfully accomplished in conjunction with antireflux surgical
      interventions when indicated.

PMID- 11845853
TI  - Incidence of major pulmonary morbidity after pneumonectomy: association with
      timing of smoking cessation.
AB  - BACKGROUND: The prevention of major pulmonary events (MPEs) after pneumonectomy
      may minimize postoperative mortality rates. The purpose of this study was to
      identify preoperative and perioperative factors associated with the development
      of MPEs after pneumonectomy to help predict which patients are at increased risk
      for MPEs. METHODS: We retrospectively reviewed the medical records of all
      patients (n = 261) who underwent pneumonectomies between January 1990 and May
      1999. We analyzed preoperative and perioperative risk factors, the primary end
      point of an MPE and the secondary end points of mortality (in-hospital or 30 days
      postprocedure), length of stay, and hospital charges. A postoperative MPE
      included only pneumonia or acute respiratory distress syndrome as defined by the
      Centers for Disease Control and the American and European Consensus Conference's
      established criteria. Simple atelectasis that did not progress to pneumonia or a
      documented aspiration was not included. RESULTS: Four patients died within 12
      hours of operation; the records of the remaining 257 patients were analyzed. An
      MPE occurred in 33 (12.8%) of 257 patients; 16 (6.2%) of 257 patients died. A
      multivariate analysis performed on relevant variables showed that only the timing
      of smoking cessation (1 month or sooner before operation) was a significant
      predictor of an MPE. Age, side of pneumonectomy, and the use of preoperative
      chemotherapy or combined chemotherapy and radiation therapy were not significant
      predictors of an MPE. An MPE significantly increased the mortality rate 2.1%
      versus 39.3%, p < 0.001). CONCLUSIONS: Mortality after pneumonectomy increased
      significantly with the development of an MPE. Patients who continue to smoke
      within 1 month of operation are at an increased risk for developing an MPE.
      Interventions to minimize MPEs may minimize the mortality rate after
      pneumonectomy.

PMID- 11845854
TI  - Current presentation and optimal surgical management of sternoclavicular joint
      infections.
AB  - BACKGROUND: Infection of the stemoclavicular joint is unusual, and treatment of
      this entity has not been standardized. We sought to characterize the current
      presentation and optimal management of this disease. METHODS: We retrospectively
      reviewed the records of the last 7 patients undergoing operation for suppurative
      infections of the stemoclavicular joint at this institution. Patients were
      interviewed regarding upper extremity function after formal joint resection.
      RESULTS: Predisposing factors were common and included diabetes mellitus (n = 2),
      clavicular fracture (n = 1), human immunodeficiency virus infection (n = 1),
      immunosuppression (n = 1), and pustular skin disease (n = 1). All patients
      presented with local symptoms including clavicular mass and tenderness. Diagnosis
      and evaluation were facilitated by cross-sectional imaging. Organisms isolated
      included Staphylococcus aureus, group G streptococcus, and Proteus and
      Propionibacterium species. Antibiotic therapy and simple drainage and debridement
      were generally ineffective, leading to recurrence of infection in 5 of 6 patients
      treated initially in this manner. Six patients were treated with resection of the
      stemoclavicular joint and involved portions of first or second ribs with soft
      tissue coverage by advancement flap from the ipsilateral pectoralis major muscle.
      Response to this therapy was excellent, with cure in all patients, no wound
      complications, and excellent upper extremity function at long-term follow-up.
      CONCLUSIONS: Aggressive surgical management including resection of the
      sternoclavicular joint and involved ribs with pectoralis flap closure would
      appear to be the preferred treatment for all but the most minor infections of the
      sternoclavicular joint. This approach has minimal impact on upper extremity
      function.

PMID- 11845855
TI  - Non-viral gene delivery to atelectatic and ventilated lungs.
AB  - BACKGROUND: Three different nonviral vectors and naked DNA were evaluated for in
      vivo transfer of plasmid DNA to rat lungs through airways in either atelectatic
      or ventilated lungs. METHODS: The F344 rats underwent instillation of 300 microg
      DNA (pCIluc, luciferase) to the left lung. Naked DNA, linear polyethylenimine,
      branched polyethylenimine, and lipid GL-67 (in either atelectatic or ventilated
      lungs) were assessed (n = 5 per group). After 24 hours, left lung PaO2 (mm Hg)
      and luciferase activity (RLU/mg) were measured. The median (range) was given, and
      the analysis of variance was applied, followed by the planned comparison on log
      transformed data. RESULTS: In atelectatic lungs, lipid GL-67 was best (927 [330
      to 4112] RLU/mg; p < 0.001 versus other groups of atelectatic lung; p < 0.001
      versus all other groups), but highest luciferase activity in all groups was
      measured in ventilated lungs using linear polyethylenimine (1,240 [922 to 2519]
      RLU/mg; p < 0.001 versus other groups of ventilated lung; p < 0.001 versus all
      other groups). In comparison with naked DNA, all nonviral vector systems
      significantly impaired PaO2 24 hours after airway transfection (p < 0.001; naked
      DNA versus all other groups). Regardless of transfection technique, PaO2 was
      worst in lungs transfected by linear polyethylenimine. CONCLUSIONS: Highest
      transfection was achieved with GL-67 in atelectatic lungs and with linear
      polyethylenimine in ventilated lungs. All gene delivery systems impaired gas
      exchange of the transduced lung in comparison with naked DNA.

PMID- 11845856
TI  - Aortic root replacement in 271 Marfan patients: a 24-year experience.
AB  - BACKGROUND: The introduction of composite graft repair of aortic root aneurysm by
      Hugh Bentall in 1968 promised Marfan patients the choice for a normal life
      expectancy. We performed our first Bentall composite graft procedure in 1976 and
      herein report our 24-year experience with 271 Marfan patients. METHODS: Between
      September 1976 and August 2000, 232 Marfan patients had a composite graft
      replacement of the aortic root, 15 patients received a homograft, and 24 had a
      valve-sparing procedure. RESULTS: Two hundred thirty-five Marfan patients
      underwent elective aortic root replacement with no 30-day mortality. Two early
      deaths occurred among 36 patients who underwent urgent or emergent operation.
      Eighty-three percent of patients in this series are currently alive. The
      actuarial freedom from thromboembolism, endocarditis, and reoperation on the
      residual aorta 20 years postoperatively was 93%, 90%, and 74%. Twenty-four
      patients have undergone valve-sparing procedures with encouraging results.
      CONCLUSIONS: Elective aortic root replacement for Marfan patients can be
      performed with low operative risk. Elective repair before the aortic root reaches
      6 cm in diameter is recommended to minimize risk of dissection and rupture.

PMID- 11845857
TI  - Repair of the thoracic aorta by transaortic stent grafting (open stenting).
AB  - BACKGROUND: The late results of direct open stent grafting of the aortic arch for
      aortic arch repair have not been reported previously. METHODS: Between September
      1997 and December 2000 19 patients underwent open stent grafting with carotid
      artery bypass for thoracic arteriosclerotic aneurysms (TAA) of the distal aortic
      arch. In addition, 21 patients underwent open stent grafting with total aortic
      arch replacement for Stanford type A acute aortic dissection and 7 patients
      underwent stenting with carotid bypass for Stanford type B chronic aortic
      dissection. RESULTS: The early mortality rate was 11% for TAA, 10% for type A
      dissection, and 0% for type B dissection. Whereas none of the TAA or type A
      dissection required a second operation on the thoracic aorta, 1 TAA patient died
      6 months postoperatively after sudden aortic rupture and 1 type B patient
      required descending aortic replacement because of ulceration caused by the stent
      graft at 11 months postoperatively. On follow-up computed tomography scan, in TAA
      patients, true aneurysms excluded by the stent graft showed early thrombosis, but
      the absorption of thrombosed aneurysms started from 1 to 6 months postoperatively
      and gradually progressed. In patients with type B chronic dissection, the false
      lumen showed early thrombosis and the true lumen was dilated at the central
      portion of the graft, which might increase turbulent flow by interaction with the
      stent. In patients with type A acute dissection, the false lumen showed both
      early thrombosis and early absorption. CONCLUSIONS: Early and late results of
      open stenting are acceptable and follow-up computed tomography scan may be able
      to predict late results of open stenting.

PMID- 11845858
TI  - Total aortic arch grafting for acute type A dissection: analysis of residual
      false lumen.
AB  - BACKGROUND: In surgery for acute type A dissection, an unresected dissection and
      residual false lumina are causes of the progression of aneurysms and ruptures. We
      grafted the ascending aorta and total arch, the maximum grafting possible through
      a median sternotomy alone, in all patients with type A dissection extending to
      the descending aorta, wherever initial tears existed in the arch. METHODS: A
      total of 37 consecutive patients with acute type A dissection underwent ascending
      and total arch grafting between August 1994 and December 2000. Cerebral
      protection was achieved by selective cerebral perfusion. The distal anastomosis
      was conducted using the "Elephant Trunk" technique. Patent false lumina were
      evaluated using computed tomography 3 months after the operation. RESULTS: The
      hospital mortality was 8.1%. No major cerebral complications were observed. The
      incidence of residual thoracic patent false lumina was 26.5%. Univariate analyses
      showed Marfan syndrome and preoperative extension of false lumina to be
      statistically significant determinants of residual thoracic false lumina. On
      multivariate analysis, no other significant independent predictor of residual
      false lumina in the thoracic aorta was found. CONCLUSIONS: Outcomes of our
      strategy were satisfactory. However, residual thoracic false lumina could not be
      prevented in 26.5% of the patients. Thus, this extended operation is indicated in
      patients with initial tears in the aortic arch or distal arch, those with Marfan
      syndrome, and young patients with preoperative patent false lumina extending to
      the abdominal aorta.

PMID- 11845859
TI  - Prosthetic replacement of the aorta is a risk factor for aortic root aneurysm
      development.
AB  - BACKGROUND: Noncompliant prostheses are used in aortic replacement. We
      hypothesized that this leads to increased distension and wall stress in the
      aortic root because of the loss of ventriculo arterial coupling. METHODS:
      Pressure relations in the aortic root caused by changes of aortic elasticity
      simulating prosthetic aortic replacement were tested in a computer model. We then
      developed an in vitro model using porcine aortas and performed in vivo
      validation. RESULTS: Findings in vitro and in vivo confirmed the predicted
      changes of the computer model. Pressure amplitude increased significantly by 17%
      after prosthetic replacement (p < 0.01). Pressure-time differential (Dp/dt) and
      dicrotic notch pressure amplitude both increased significantly. Echocardiography
      demonstrated systolic aortic root distension with percentage area change
      increasing in vitro from 28.2%+/-9.7% to 35.9%+/-10% (p < 0.05) and in vivo from
      13.3%+/-3.1% to 24.3%+/-3.1% (p < 0.0001). Aortic root wall stress increased
      markedly. CONCLUSIONS: Replacement of the aorta with vascular prostheses causes
      important negative alterations of hemodynamics and increases in wall stress.

PMID- 11845860
TI  - Does ministernotomy improve postoperative outcome in aortic valve operation? A
      prospective randomized study.
AB  - BACKGROUND: The aim of this study was to compare the postoperative outcome
      obtained in patients undergoing elective aortic valve operation, either through
      ministernotomy or conventional sternotomy. METHODS: Between January 1999 and July
      2001, 80 consecutive patients undergoing elective aortic valve replacement were
      randomly divided into two groups: group I (n = 40 patients) undergoing a
      ministernotomy approach (reversed-C or reversed-L), and group II (n = 40
      patients) undergoing conventional sternotomy. RESULTS: The length of skin
      incision was significantly shorter in group I than in group II (8.2+/-1.3 cm
      versus 23.7+/-2.6 cm, p < 0.001). No significant differences were found in
      cardiopulmonary bypass duration, associated procedures, or aortic cross-clamping
      times. Total operating time was 3.7+/-0.46 hours in group I compared with 3.4+/
      0.6 hours in group II (p = 0.014). A similar incidence of cardiac, neurologic,
      infective, and renal complications between groups was found. Mean mediastinal
      drainage and mean blood transfusions (amount of blood transfused) per patient
      were greater in group II (p < 0.004 and p < 0.001, respectively). Twenty-five
      (62.5%) patients in group II and 15 (37.5%) patients in group I required
      postoperative blood transfusion (p = 0.04). Mechanical ventilation time was
      significantly longer in group II (6.2+/-1.8 hours versus 4.4+/-0.9 hours, p =
      0.006). Five days after the surgical procedure, spirometric data analysis
      demonstrated a significantly lower total lung capacity and maximum inspiratory
      and expiratory pressures in group II compared with group I (p = 0.003, p = 0.007,
      and p < 0.001, respectively). CONCLUSIONS: Our results showed that ministernotomy
      had not only important cosmetic advantages but also beneficial effects in blood
      loss and transfusion, postoperative pain, and probably in sternal stability.
      Ministernotomy also improved recovery of respiratory function and allowed earlier
      extubation and hospital discharge.

PMID- 11845861
TI  - Prosthetic replacement of tricuspid valve: bioprosthetic or mechanical.
AB  - BACKGROUND: Tricuspid valve replacement is one of the most challenging operations
      in cardiac surgery. Selection of the suitable prosthesis is still debatable.
      METHODS: In our institution, between January 1980 and December 2000, 129
      tricuspid valve replacements were performed in 122 patients (14.7%).
      Bioprosthetic valves were used in 32 patients, whereas 97 patients had mechanical
      valve implantation. Twenty-two percent of replacements were done on men. Mean age
      was 35.27+/-11.56 years. In all patients, initially an annuloplasty technique was
      tried. Tricuspid valve replacement was performed when annuloplasty was not
      sufficient. In most of the cases, tricuspid valve interventions were done under
      cardiopulmonary bypass and on a beating heart. RESULTS: Early mortality was
      24.5%. Patients were followed for 2 to 228 months. Seven patients underwent
      reoperation because of tricuspid valve dysfunction (7.6%). Nine patients died
      during the follow-up period. Late mortality was 9.7%. Actuarial estimates of
      survival in 20 years of follow-up for all tricuspid prosthetic valves, mechanical
      valves, and bioprosthetic valves were 65.1%+/-9.3%, 68.3%+/-10.6%, and 54.8%+/
      12.1%, respectively. For the bioprosthetic valve group, freedom from structural
      valve degeneration was 90%+/-5.5%; for the mechanical valve group, freedom from
      deterioration, endocarditis, and leakage was 97.8%+/-4.2%, and freedom from
      thromboembolism was 92.6%+/-6.9%. CONCLUSIONS: We found that there was no
      statistically significant difference between the two groups in terms of early
      mortality, re-replacement, and midterm mortality (p > 0.05). Nevertheless, we
      recommend low profile modern bileaflet mechanical valves for prosthetic
      replacement of the tricuspid valve, due to their favorable hemodynamic
      characteristics and durability.

PMID- 11845862
TI  - Up to 8-year follow-up of valve replacement with carbomedics valve.
AB  - BACKGROUND: The aim of this study was to report midterm valve replacement (VR)
      results with the Carbo-Medics valve (Sulzer Carbomedics, Austin, TX). METHODS:
      From 1991 to 1999, 468 patients aged 13 to 76 years (mean 56 years) underwent VR
      with CarboMedics valve: 239 aortic (A), 167 mitral (M), and 62 A+M or double
      valve replacement (DVR). Mean follow-up time was 4.4 years; follow-up was 99.1%
      complete for 2,016 patient-years (PY). The anticoagulation level was targeted to
      an international normalized ratio of 1.47 to 2.8. RESULTS: The hospital mortality
      rate was 1.2%. Actuarial analysis for the entire group at 7 years for survival
      was 87%+/-2.3%. Freedom from valve-related death was 94%+/-1.9%. Freedom from
      thromboembolic and bleeding events, respectively, were as follows: for AVR, 82%+/
      4.9% (2.4%/PY) and 88%+/-2.9% (1.6%/PY); for MVR, 95%+/-2.1% (0.8%/PY) and 91%+/
      3.1% (1.3%/PY); and for DVR, 96%+/-3.2% (0.7%/PY) and 85%+/-9.7% (1.0%/PY).
      Actuarial freedom from reoperation was 98%+/-1.4%. CONCLUSIONS: The CarboMedics
      valve can be implanted with satisfactory early mortality and a low incidence of
      valve-related events even under low-intensity anticoagulation, as shown in a
      Japanese population.

PMID- 11845863
TI  - A decade of change--risk profiles and outcomes for isolated coronary artery
      bypass grafting procedures, 1990-1999: a report from the STS National Database
      Committee and the Duke Clinical Research Institute. Society of Thoracic Surgeons.
AB  - BACKGROUND: The Society of Thoracic Surgeons National Adult Cardiac Database is
      the largest voluntary clinical database in medicine. Using this database we
      examined changes in the risk profile of patients undergoing isolated coronary
      artery bypass grafting (CABG) and their outcomes during the decade 1990 to 1999.
      METHODS: Trends in 23 preoperative risk factors were tracked for CABG cases
      during this decade. Using a multivariate logistic risk model, we also determined
      the degree to which operative risk and risk-adjusted operative mortality changed
      during this 10-year interval. RESULTS: Between 1990 and 1999, 1,154,486 patient
      records were harvested by the Society of Thoracic Surgeons National Adult Cardiac
      Database for isolated CABG procedures performed at 522 Society of Thoracic
      Surgeons participant sites in the United States and Canada. Over time, CABG
      patients were more likely to be older (mean age 63.7 in 1990, 65.1 in 1999), of
      female gender (25.7% women in 1990, 28.7% in 1999), and have a history of
      smoking, diabetes mellitus, renal failure, hypertension, stroke, chronic lung
      disease, New York Heart Association functional class IV, and three-vessel disease
      (p < 0.0001). Patients' predicted operative risk increased by 30.1%, from 2.6% in
      1990 to 3.4% in 1999. Despite higher risk, observed operative mortality decreased
      by 23.1%, from 3.9% in 1990 to 3.0% in 1999 (p < 0.0001). During the decade, a
      Medicare-aged subset (n = 629,174) experienced similar increases in risk and
      declines in mortality. CONCLUSIONS: Patients referred for isolated CABG are
      significantly older, sicker, and have a higher risk than a decade ago. Despite
      this, CABG mortality rates have declined substantially. These results highlight
      the excellent progress in the care of CABG patients achieved during the past
      decade.

PMID- 11845864
TI  - Operative and 5-year outcomes of combined carotid and coronary revascularization:
      review of a large contemporary experience.
AB  - BACKGROUND: Surgical treatment of concomitant coronary and carotid disease is
      controversial. Studies comparing staged versus combined coronary artery bypass
      grafting and carotid endarterectomy (CABG/CEA) report varying and often
      conflicting operative results. Also, few studies have investigated the long-term
      outcomes of combined surgery. METHODS: We reviewed the operative outcome and 5
      year survival results of 189 consecutive patients (69+/-9 years old, 66 [35%]
      female patients) who underwent combined CABG/CEA between 1994 and 1999. Survival
      follow-up was conducted in February 2001 and the incidence of late stroke,
      carotid surgery, and myocardial infarction was investigated in all surviving
      patients by mail survey. A phone interview was done by a surgeon of patients with
      late strokes or repeated CEA. RESULTS: Operative death occurred in 5 of 189
      patients (2.65%) 4 of which were in-hospital deaths. A total of 5 (2 permanent, 3
      transient [2.65%]) perioperative strokes were documented in these patients, and 1
      of the perioperative strokes patients died in the hospital. In all, 156 of 189
      patients (82.5%) were alive at the time of the study and completed surveys were
      collected from 153 of 156 patients (98%). Of these 153 patients, 4 reported a
      late stroke (2.6%), 5 suffered a myocardial infarction (3.3%), and 16 (10.5%)
      underwent subsequent CEA (7 ipsilateral to original CEA). Angioplasty (3 of 153,
      2.0%) and redo surgery (1 of 153, 0.66%) occurred infrequently. Median survival
      follow-up was 51 months (range 12 to 84), and the corresponding 5-year Kaplan
      Meier survival was 79.4%. This survival was similar to that of age-matched
      isolated CABG patients (n = 532) with documented history of cerebrovascular
      disease but no surgical carotid lesions. CONCLUSIONS: Our results suggest that
      combined CABG/ CEA is safe and may in fact reduce the risk of adverse outcomes in
      the intermediate term compared with age and risk-matched patients. We speculate
      the latter may be attributable to a cerebrovascular protective effect of CABG/CEA
      pending verification by randomized trials. An economic benefit of CABG/CEA may
      also be inferred from avoiding separate coronary and carotid operations and
      reduction in the high costs of perioperative stroke.

PMID- 11845865
TI  - Coronary artery bypass grafting with left internal mammary artery and right
      gastroepiploic artery, with and without bypass.
AB  - BACKGROUND: Total arterial and off-pump revascularization are increasingly used
      in coronary artery bypass grafting. This study describes our experience with the
      exclusive use of both left internal thoracic artery and gastroepiploic artery by
      means of a median sternotomy, with and without cardiopulmonary bypass, in a
      subgroup of patients with two-vessel disease. METHODS: From January 1995 to July
      2000, 171 consecutive patients were reviewed in a prospective database. Ninety
      one patients underwent coronary artery bypass grafting without cardiopulmonary
      bypass (group A), and 80 patients were operated on under cardiopulmonary bypass
      with aortic cross-clamp and cardioplegia (group B). RESULTS: Patient data were
      similar in both groups except for the Euroscore (mean; 3.4+/-6.1, group A versus
      2.5+/-4.5, group B; Euroscore > 6: 26.4%, group A versus 10%, group B; p < 0.05)
      and ejection fraction (mean, 54.6%+/-15.8%, group A versus 63.1%+/-12.7%, group
      B; p < 0.001). Severe aortic calcification was present in 6 group A patients,
      versus no patient in group B. Operative time was shorter in group A (185 versus
      213 minutes, p < 0.0001), with less distal anastomoses (2.26 versus 2.5, p <
      0.05). Conversion to cardiopulmonary bypass occurred in 1 patient, who was
      excluded from the study. Bleeding was higher in group A (852.6+/-288 mL versus
      712.4+/-274 mL, p < 0.05), but transfusion was similar in both groups. Atrial
      fibrillation, postoperative inotropic support, and hospital stay were similar in
      both groups. Myocardial infarction was less frequent in group A (1 versus 4).
      Postoperative intraaortic balloon pump was used in 2 patients (group B). One
      patient died (group A) and 1 had an embolic stroke (group B). After discharge, 2
      more patients died (group A, day 91; group B day 141), and 1 patient suffered an
      embolic stroke (group B). One patient in each group presented with dysfunction of
      the gastroepiploic artery graft requiring successful percutaneous transluminal
      angioplasty on the right posterolateral artery. CONCLUSIONS: These results
      suggest that off-pump coronary artery bypass grafting using the left internal
      thoracic artery and gastroepiploic artery is safe even in high-risk patients.
      This approach allows an absolute no-touch technique of the aorta.

PMID- 11845866
TI  - Feasibility and suitability of the routine use of bilateral internal thoracic
      arteries.
AB  - BACKGROUND: It has been demonstrated that bilateral use of internal thoracic
      arteries (ITAs) confers better long-term results in patients than does unilateral
      use. However, routine use of bilateral ITAs has usually been avoided. METHODS:
      Since 1997, we have used bilateral ITAs extensively for patients who required
      multivessel bypasses. Recently, 243 consecutive patients, including 127 diabetic
      patients, were reviewed. RESULTS: Every patient received at least one ITA graft,
      and 200 patients (82%) received bilateral ITAs. The majority (93%) of ITA grafts
      were used as in situ grafts. The hospital mortality rate was 0.41%, and deep
      sternal infections were observed in 5 patients (2.0%). There was no difference in
      the incidence of chest wound infection between the group treated with bilateral
      ITA grafting and that treated by unilateral ITA grafting. CONCLUSIONS: These
      observations suggest that ITAs can be used bilaterally for treatment in the
      majority of patients who require multivessel bypass, with low mortality and
      morbidity.

PMID- 11845868
TI  - Endoscopic versus open saphenous vein harvest: a comparison of postoperative
      wound complications.
AB  - BACKGROUND: Wound complications associated with long incisions used to harvest
      the greater saphenous vein are well documented. Recent reports suggest that
      techniques of endoscopic vein harvest may result in decreased wound
      complications. A prospective, nonrandomized study was developed to compare
      outcomes of open versus endoscopic vein harvest procedures. METHODS: There were
      106 patients in the open vein harvest group, and 154 patients in the endoscopic
      vein harvest group. Patient characteristics and demographics were similar in both
      groups. Wound complications identified were dehiscence, drainage for greater than
      2 weeks postoperatively, cellulitis, hematoma, and seroma/lymphocele. RESULTS:
      Wound complications were significantly less in the endoscopic vein harvest group
      (9 of 133, 6.8%) versus the open vein harvest group (26 of 92, 28.3%), p less
      than 0.001. By multivariable analysis with logistic regression, the open vein
      harvest technique was the only risk factor for postoperative leg wound
      complication (relative risk 4.0). CONCLUSIONS: Endoscopic vein harvest offered
      improved patient outcomes in terms of wound healing compared with the open vein
      harvest technique.

PMID- 11845867
TI  - Interaction between vasodilators and vasopressin in internal mammary artery and
      clinical significance.
AB  - BACKGROUND: Arginine vasopressin (AVP) has recently been demonstrated as an
      alternative in the treatment of severe refractory vasodilatation in coronary
      artery bypass grafting. However, AVP may be a spasmogen for graft spasm. We
      compared the in vitro antispastic effect among calcium-channel antagonists
      (nifedipine, diltiazem, and verapamil), nitroglycerin, and the highly selective
      AVP (V1) receptor antagonist [1-deaminopenicillamine, 4-valine, 8-D-arginine]
      vasopressin. METHODS: Human internal mammary artery segments (n = 218) were
      studied in organ baths. The inhibitory effects of the above vasodilators on AVP
      mediated contraction were studied in two ways: relaxation with AVP precontraction
      and depression of the AVP-induced contraction after pretreatment with
      vasodilators. RESULTS: All three calcium-channel antagonists caused limited
      relaxation (18.3%+/-5.4% for nifedipine, n = 11; 22.2%+/-3.8% for verapamil, n =
      10; and 26.2%+/-7.5% for diltiazem, n = 9). The plasma concentration of calcium
      channel antagonists had no significant depression effect on the AVP-induced
      contraction. In contrast, [1-deaminopenicillamine, 4-valine, 8-D-arginine]
      vasopressin caused full (100%, n = 11) and nitroglycerin caused nearly full
      (93%+/-3%, n = 10) relaxation. Pretreatment with [1-deaminopenicillamine, 4
      valine, 8-D-arginine] vasopressin (10(-8), 10(-7), or 10(-6) mol/L, respectively)
      significantly increased the effective concentration for 50% of the AVP-induced
      contraction (10(-8.6)+/-10(0.1) mol/L, p = 0.009; 10(-7.8)+/-10(0.07) mol/L, p =
      0.000; or 10(-6.9)+/-10(0.11) mol/L, p = 0.000 versus the control, 10(-9.24)+/
      10(0.16) mol/L). However, nitroglycerin only slightly depressed the AVP-induced
      contraction. CONCLUSIONS: [1-Deaminopenicillamine, 4-valine, 8-D-arginine]
      vasopressin may provide specific antispastic effect in either prophylaxis or
      treatment of the AVP-related vasospasm in the internal mammary artery.
      Nitroglycerin may be effective in treatment but has little effect on prophylaxis.
      Use of calcium-channel antagonists may have little benefit in AVP-related
      vasospasm.

PMID- 11845869
TI  - Beneficial effects of inhaled nitric oxide in adult cardiac surgical patients.
AB  - BACKGROUND: Pulmonary hypertension with associated right ventricular dysfunction
      may complicate the postoperative cardiac patient despite maximum pharmacologic
      and ventilatory support. The purpose of this study was to retrospectively review
      our experience with inhaled nitric oxide (INO) in adult postoperative cardiac
      patients with pulmonary hypertension. METHODS: We retrospectively reviewed the
      medical records of 17 adult cardiac patients treated with INO postoperatively
      between November 1998 and February 2000. The INO was used to manage pulmonary
      hypertension postoperatively in patients who had undergone coronary artery bypass
      graft (CABG) (n = 13), valve operation (n = 3), and combined CABG/aortic valve
      replacement (n = 1). Hemodynamic and respiratory measurements before INO and
      again 6 hours after administration were examined. Student's t test was used to
      analyze the data. RESULTS: Inhaled nitric oxide (20 ppm to 30 ppm) was
      administered for a median duration of 30.2 hours. The group, as a whole,
      demonstrated a significant decrease in both mean pulmonary artery pressure and
      right ventricular stroke work index. In addition, a significant increase in
      posttherapeutic cardiac index and Pao2/Fio2 ratio was observed. The vasodilatory
      effects of nitric oxide were specific to the pulmonary circulation as no
      significant change in mean arterial pressure was noted. Overall mortality was 6%.
      CONCLUSIONS: Inhaled nitric oxide effectively and selectively lowered right
      ventricular afterload and right ventricular work in critically ill adult cardiac
      patients with acute pulmonary hypertension.

PMID- 11845870
TI  - Late cardiac reoperation after cardiac transplantation.
AB  - BACKGROUND: The intermediate and long-term results of cardiac transplantation
      continue to improve. Subsequent cardiac procedures may be required to extend
      patient survival and protect graft function. METHODS: The medical records of all
      adult and pediatric cardiac transplant recipients who underwent a subsequent
      cardiac procedure at our institution were reviewed. RESULTS: Three hundred sixty
      patients have undergone primary orthotopic transplantation in our institution.
      Seventeen patients (12 adults, 5 children) underwent a subsequent procedure
      requiring cardiopulmonary bypass including cardiac retransplantation (10),
      coronary artery bypass grafting (3), ascending aortic replacement (2), tricuspid
      valve repair (1), and myotomy and myomectomy (1 patient). Mean interval from time
      of transplantation to second procedure was 8.3 years. There was one perioperative
      death. Two patients, both retransplants, died late postoperatively at 22 and 84
      months, respectively. Overall mean follow-up in the late survivors is 26.6
      months. All survivors are currently asymptomatic and doing well. CONCLUSIONS: A
      variety of subsequent cardiac procedures, in addition to retransplantation, can
      be performed safely in carefully selected cardiac transplant recipients. The
      intermediate term results are gratifying in terms of survival and freedom from
      symptoms.

PMID- 11845871
TI  - Extracorporeal membrane oxygenation support for adult postcardiotomy cardiogenic
      shock.
AB  - BACKGROUND: Postcardiotomy cardiogenic shock occasionally develops in patients
      who have undergone cardiac procedures. We report our experience using
      extracorporeal membrane oxygenation (ECMO) in adult patients with postcardiotomy
      cardiogenic shock, and analyze the factors that affected outcomes for these ECMO
      patients. METHODS: We retrospectively reviewed the medical records of ECMO
      patients. RESULTS: From August 1994 to May 2000, 76 adult patients (48 men, 28
      women; mean age, 56.8+/-15.9 years) received ECMO support for postcardiotomy
      cardiogenic shock at the National Taiwan University Hospital. The mean ECMO blood
      flow was 2.53+/-0.84 L/min. The cardiac operations included coronary artery
      bypass grafting (n = 37), coronary artery bypass grafting and valvular operation
      (n = 6), valvular operation alone (n = 14), heart transplantation (n = 12),
      correction of congenital heart defects (n = 3), implantation of a left
      ventricular assist device (n = 2), and aortic operations (n = 2). Fifty-four
      patients received ECMO support after intraaortic balloon pumping, but 22 patients
      directly received ECMO support. Two patients were bridged to heart
      transplantation and two bridged to ventricular assist devices. Thirty patients
      died on ECMO support. The causes of mortality included brain death (n = 3),
      refractory arrhythmia (n = 2), near motionless heart (n = 2), acute graft
      rejection (n = 1), primary graft failure (n = 1), uncontrolled bleeding (n = 5),
      and multiple organ failure (n = 16). Twenty-two patients were weaned off ECMO
      support but presented intrahospital mortality. The cause of mortality included
      brain death (n = 1), sudden death (n = 4), and multiple organ failure (n = 17).
      Twenty patients were weaned off ECMO support and survived to hospital discharge.
      During the follow-up of 33+/-22 months, all were in New York Heart Association
      functional status I or II except two cases of late deaths. Among the ECMO-weaned
      patients, "dialysis for acute renal failure" was a significant factor in reducing
      the chance of survival. CONCLUSIONS: The ECMO provided a satisfactory partial
      cardiopulmonary support to patients with postcardiotomy cardiogenic shock, and
      allowed time for clinicians to assess the patients and make appropriate
      decisions.

PMID- 11845872
TI  - And hemolysis goes on: ventricular assist device in combination with veno-venous
      hemofiltration.
AB  - BACKGROUND: Ventricular Assist Device (VAD) is an accepted treatment as a bridge
      to cardiac transplantation, and may be of help in patients as destination therapy
      for end-stage cardiac failure. The low output state associated with end-stage
      cardiac failure predisposes patients to renal dysfunction and the need for short
      term renal support. The use of cardiopulmonary bypass for VAD insertion, VAD, and
      hemofiltration expose the blood to mechanical trauma and activated inflammatory
      cascades that can result in hemolysis. This produces free hemoglobin, a known
      nephrotoxin; this is a further renal insult. This study assesses the effect of
      VAD alone and in combination with continuous veno-venous hemofiltration (CVVHF)
      on hemolysis. METHODS AND RESULTS: From July 1999 to December 2000, Thoratec VAD
      was used in 11 patients. Nine (all males) were included in this study as all had
      laboratory profiles. Hemolysis was quantified by plasma free hemoglobin (PFHb)
      and hydroxybuterate dehydrogenase (HBD) levels measured daily, defined as PFHb
      level greater than 40 mg/L and HBD greater than 250 IU/L. Data relate to the
      following time intervals while the VAD was still in situ: T1 = 24 hours post-VAD
      insertion, T2 = 24 hours post-CVVHF start, T3 = 48 to 72 hours with the same
      CVVHF circuit, T4 = 24 hours post-stopping of CVVHF, and T5 = CVVHF off for over
      48 hours. The mean (SD) PFHb levels were 19.6 (10.9) at T1, 31.7 (0.6) at T2,
      93.7 (16.4) at T3 (p < 0.05), 32.5 (20.9) at T4, and 14.2 (3.8) at T5 (p < 0.05).
      These changes were paralleled by the mean (SD) HBD levels: T1 = 1,337 (616), T2 =
      2,025 (509), T3 = 2,676 (1,170) (p < 0.05), T4 1,780 (618), and T5 = 1,310 (436).
      CONCLUSIONS: Thoratec VAD was associated with a mild degree of hemolysis. This
      was worsened by concomitant use of CVVHF. The effect was accentuated if the same
      CVVHF circuit was used for over 48 hours but was reversible within 24 hours of
      stopping the hemofilter.

PMID- 11845873
TI  - Hepatic dysfunction after left ventricular mechanical assist in patients with end
      stage heart failure: role of inflammatory response and hepatic microcirculation.
AB  - BACKGROUND: In the condition of preexisting vital organ failure induced by heart
      failure, hepatic failure often progresses despite establishment of adequate
      hemodynamic support through a left ventricular assist device (LVAD) and results
      in a high mortality rate. We hypothesized that inflammatory responses, including
      those induced by infection and their influence on organ perfusion, may contribute
      to the pathogenesis of this progressive hepatic failure and subsequent multiple
      organ failure as reported in the current investigation on multiple organ failure
      after major surgery or trauma. METHODS: Hepatic function and its relation to
      inflammatory response and hepatic microcirculation were evaluated in 16
      consecutive patients who received an implantation of LVAD for end-stage
      cardiomyopathy, between 1992 and 2000. Patients were divided into two groups: 5
      patients who died from multiple organ failure after severe hepatic failure (group
      1) and 11 patients who did not develop severe hepatic failure (group 2). Serum
      levels of CRP, interleukin (IL)-6, IL-8, and serum hyaluronan, a known indicator
      of hepatic sinusoidal function, were measured pre- and postoperatively in both
      groups. RESULTS: Serum ALT and AST levels during LVAD support were similar in the
      two groups. Serum total bilirubin (T-Bil), CRP, IL-6, and IL-8 levels before and
      during the first 20 days of LVAD support were significantly higher in group 1
      than those in group 2 (p < 0.01 to 0.05). Serum hyaluronan levels in both groups
      were significantly correlated with T-Bil levels (r = 0.60, p < 0.05 in group 1; r
      = 0.68, p < 0.0001 in group 2). Histopathological examination by transvenous
      liver biopsy in a group 1 patient showed hepatic sinusoidal damage as well as
      cholestasis and fibrosis. CONCLUSIONS: Patients with hyperbilirubinemia and
      inflammatory reactions before LVAD support showed increased hyperbilirubinemia
      and inflammatory cytokine and hyarulonan levels despite adequate hemodynamics
      achieved under LVAD support. These results suggest that inflammatory response
      contributes to subsequent aggravation of hepatic dysfunction, probably with
      underlying and continuing derangement in hepatic sinusoidal microcirculation even
      under systemic circulatory support.

PMID- 11845874
TI  - Non-blood contacting biventricular support for severe heart failure.
AB  - BACKGROUND: Direct mechanical ventricular actuation (DMVA) is a non-blood
      contacting method of biventricular support. DMVA employs a vacuum attached,
      pneumatically regulated, flexible membrane to transfer both systolic and
      diastolic forces to the ventricular myocardium. The purpose of this study was to
      determine if DMVA effectively restores pump performance when applied to the
      severely failing heart. METHODS: Bovines (n = 10) underwent thoracotomy and were
      instrumented for continuous hemodynamic monitoring. Cardiac failure was induced
      by beta1-blockade to achieve a cardiac index of < 1.5 l/min/m2 for 1 hour. Heart
      rate was maintained at 100 bpm by atrioventricular sequential pacing. Synchronous
      DMVA support was then applied for 3 hours. RESULTS: Eight animals achieved
      significant reductions in cardiac index and mean arterial pressures (35%* and
      43%* control, respectively; *p < 0.05). DMVA restored cardiac index to baseline
      and significantly increased arterial pressures (p < 0.05; DMVA versus cardiac
      failure). Pulmonary flow and mean pulmonary artery pressures were similar to
      baseline during DMVA (p = NS). Pathologic exam did not demonstrate evidence of
      significant device trauma. CONCLUSIONS: DMVA support can effectively restore pump
      performance of the acutely failing heart. Synchronization may be inherent to the
      stimulus of cardiac compression. These data further substantiate DMVA's potential
      as an adjunct to the field of circulatory support.

PMID- 11845875
TI  - A biomechanical comparison of three sternotomy closure techniques.
AB  - BACKGROUND: A biomechanical study of three sternotomy closure techniques (figure
      of-eight stainless-steel wires, Pectofix Dynamic Sternal Fixation [DSF] stainless
      steel plates, and figure-of-eight stainless-steel cables) was conducted to
      compare strength and stiffness variables in three clinically relevant loading
      modes (anterior-posterior shear, longitudinal shear, and lateral distraction).
      METHODS: All tests were conducted on polyurethane foam sternal models that
      simulate the properties of cancellous bone. Each model was divided longitudinally
      and reconstructed using one of the sternotomy closure repair techniques. Tests
      were performed using a materials testing system that applies a continuously
      increasing amount of force in one direction to the model until it
      catastrophically breaks. A total of six trials of each fixation type in each of
      three test groups were prepared and tested, for a total of 54 tests. Strength and
      stiffness variables as well as a post-yield analysis of failure were evaluated.
      RESULTS: Sternums repaired using the DSF plate system are a more rigid construct
      than sternums repaired using the stainless-steel wires or cables in the
      distraction and transverse shear modes and they are not significantly different
      from sternums repaired with wires or cables in the longitudinal shear mode. The
      DSF plate system offers a 25% improvement in resistance to failure (yield)
      compared to wires when a transverse shear force is applied to the model. The
      cable system had a higher resistance to failure than the wires in all modes
      although the differences were not statistically significant. Additionally, the
      DSF plate system provides substantial reduction of the implant's cutting into the
      sternal model under loading as evidenced by the post-yield displacement when
      compared with either cables or wires for the distraction and longitudinal shear
      modes. For the transverse shear mode, the cables or wires would completely fail
      at the load for which cutting begins for the DSF. CONCLUSIONS: Both the DSF plate
      system and the stainless-steel cable system offer important advantages over
      figure-of-eight wire for sternal closure.

PMID- 11845876
TI  - Ischemic preconditioning and Na+/H+ exchange inhibition improve reperfusion ion
      homeostasis.
AB  - BACKGROUND: Intramyocyte sodium (Na+) increases during ischemia and reperfusion,
      which causes myocardial calcium (Ca2+) uptake and leads to myocyte injury or
      death. This study determines if ischemic preconditioning and myocyte sodium
      hydrogen ion (Na+-H+) exchange (NHE) inhibition decreases Na+ gain that otherwise
      occurs with cardioplegic arrest and reperfusion. METHODS: Pigs had 1 hour of
      cardioplegic arrest followed by reperfusion. Group 1 had no intervention
      (controls). Group 2 received dimethyl amiloride (DMA, an NHE inhibitor), and
      group 3 had ischemic preconditioning before cardioplegic arrest. Precardioplegia
      to postreperfusion change in intramyocyte ion content was measured with atomic
      absorption spectrometry. The time to initial electrical activity and number of
      defibrillations needed to establish an organized rhythm postreperfusion were used
      as electrophysiologic variables to measure ischemia-reperfusion injury. RESULTS:
      Intramyocyte Na+ content for group 1 increased from 45.9+/-6.7 to 61.9+/-22.5
      micromol/g (p = 0.02). Group 2 had an insignificant decrease in intramyocyte Na+
      of 27.7+/-19.58 micromol/g (p = 0.06), and group 3 had an insignificant decrease
      of 10.8+/-46.33 micromol/g (p = 0.48). Interstitial water increased significantly
      in all groups, but there were no significant increases in intramyocyte water
      content. Electrophysiologic recovery was similar for all three groups.
      CONCLUSIONS: The NHE inhibition and ischemic preconditioning each eliminated the
      increase in intramyocyte Na+ content that otherwise occurred with cardioplegic
      arrest and reperfusion in this porcine model. Because their mechanisms are
      distinct, it is possible that an additive beneficial effect against ischemia
      reperfusion injury can be achieved by using NHE inhibition together with a
      preconditioning stimulus as prereperfusion therapy.

PMID- 11845878
TI  - Glucose-insulin-potassium solution improves left ventricular mechanics in
      diabetes.
AB  - BACKGROUND: The mechanism by which glucose-insulin-potassium solutions enhance
      recovery of left ventricular function after myocardial ischemia in diabetic
      patients is not well understood. We evaluated the effect of glucose-insulin
      potassium on ventriculoarterial coupling and left ventricular mechanics in a
      chronic ovine model of diabetes. METHODS: Diabetes was induced in 6 sheep with
      streptozotocin. After 6 months of diabetes, the response of the left ventricular
      pressure-volume relationship to 60 minutes of intravenous glucose-insulin
      potassium solution (1,000 mL of 5% dextrose in water, 100 IU of regular insulin,
      90 mmol of KCl at 1.5 mL x kg(-1) x h(-1)) was determined. RESULTS: Glucose
      insulin-potassium solution increased end-systolic elastance 68% (p = 0.01) and
      improved ventriculoarterial coupling (1.7+/-0.3 to 1.0+/-0.1; p < 0.01).
      Potential energy decreased 35% (p = 0.01), and pressure-volume area decreased 20%
      (p = 0.01). However, stroke work did not change; therefore stroke work efficiency
      increased from 50.1%+/-3.5% to 60.2%+/-5.1% (p = 0.01). CONCLUSIONS: Glucose
      insulin-potassium solution improves left ventricular contractility and
      ventriculoarterial coupling in diabetes. Left ventricular mechanics is improved
      by decreasing total mechanical work without significantly affecting stroke work,
      resulting in improved stroke work efficiency. Improved efficiency facilitates
      understanding of the enhanced tolerance to myocardial ischemia afforded by
      glucose-insulin-potassium solution.

PMID- 11845877
TI  - Myocardial protection by PJ34, a novel potent poly (ADP-ribose) synthetase
      inhibitor.
AB  - BACKGROUND: The activation of poly (ADP-ribose) synthetase plays an important
      role in the pathogenesis leading to myocardial ischemia-reperfusion injury. The
      aim of this study was to determine if a novel potent inhibitor of poly (ADP
      ribose) synthetase, PJ34, provides myocardial protection. METHODS: Pigs were
      subjected to 60 minutes of regional ischemia followed by 180 minutes of
      reperfusion. Ten mg/kg of PJ34 (PJ34; n = 6) was administrated intravenously
      (treated group) from 15 to 5 minutes before reperfusion followed by 3 mg/kg/hour
      of PJ34 from 5 minutes before reperfusion to the end of 180 minutes reperfusion.
      Control pigs (n = 7) received vehicle only. Arterial and left ventricular
      pressure and coronary flow were monitored. RESULTS: The PJ34 showed significant
      reduction on infarct size (37.5%+/-4.5% and 50.5%+/-4.8% of the area at risk) for
      PJ34 and control pigs groups, respectively, (p < 0.05). Significant reduction in
      postsystolic shortening, as well as improvement on segment shortening, and
      positive first derivative of pressure over time (+dP/dt) maximum were also
      observed in PJ34 versus control pigs (p < 0.05). CONCLUSIONS: Our results suggest
      that PJ34 provides cardioprotection by decreasing myocardial infarct size and
      enhancing postischemic regional and global functional recovery.

PMID- 11845879
TI  - Skeletal muscle ventricle aortic counterpulsation: function during chronic heart
      failure.
AB  - BACKGROUND: Skeletal muscle ventricles (SMVs) are pumping chambers formed from
      latissimus dorsi muscle. The SMV aortic counterpulsator model has been proven to
      be stable in the long term and provide effective diastolic pressure augmentation
      in normal dogs. This study seeks to prove that the aortic counterpulsator model
      can function effectively in chronic heart failure. METHODS: In 6 dogs,
      pericardium-lined SMVs were created from latissimus dorsi muscle and electrically
      conditioned for fatigue resistance. Each SMV was attached to the descending
      thoracic aorta with a two-limb bifurcated graft and the aorta ligated between the
      limbs. The SMV was stimulated to contract during cardiac diastole at 1:2 to 1:3
      ratio. Rapid ventricular pacing was initiated at 220 to 230 beats/min for 7 weeks
      to induce chronic heart failure. RESULTS: SMV contraction resulted in
      augmentation of the diastolic pressure time-index by 12.1% (32.8+/-15.4 versus
      36.1+/-14.7 mm Hg-s, p < 0.05) at baseline, then by 33.6% (12.9+/-4.4 versus
      16.8+/-4.3 mm Hg-s, p < 0.05) after 7 weeks of rapid ventricular pacing. After 7
      weeks of rapid ventricular pacing, SMV counterpulsation provided significant
      afterload reduction with increases in peak left ventricular ejection velocity and
      stroke volume of 22.7% (142+/-55 versus 168+/-45 mL/s, p < 0.05) and 6.2% (13.0+/
      5.1 versus 13.7+/-5.2 mL, p < 0.05), respectively. Coronary blood flow was
      measured in 3 animals at the 7-week measurement; augmentation averaged 47.6%
      (0.357+/-0.29 versus 0.432+/-0.26 mL/beat, p < 0.05). CONCLUSIONS: The SMV aortic
      counterpulsator provides improved cardiac assistance relative to the failing
      heart.

PMID- 11845880
TI  - Intermediate results of the anatomic repair for congenitally corrected
      transposition.
AB  - BACKGROUND: Anatomic repair of congenitally corrected transposition of the great
      arteries has several advantages over the traditional approach but lacks long-term
      evaluation. METHODS: The data on 12 patients who had the procedure between
      January 1989 and June 2000 were retrospectively reviewed. Associated lesions
      included ventricular septal defect in 12 patients, pulmonary stenosis in 10
      patients, and moderate to severe tricuspid valve regurgitation in 4 patients.
      Mean age at operation was 9+/-3.6 months. All patients had venous switch Mustard
      procedure. Tunneling of the morphologic left ventricle through the ventricular
      septal defect to the aorta with insertion of right ventricular to pulmonary
      artery conduit was performed in 10 patients, and arterial switch operation in 2.
      Concomitant tricuspid valvuloplasty was done in 2 patients and ventricular septal
      defect enlargement in 1. RESULTS: There was one hospital death (9%) in the
      patient who needed ventricular septal defect enlargement. Complications included
      atrioventricular block requiring pacemaker insertion in 1 patient (9%) and
      superior vena caval obstruction in 1 patient (9%). Follow-up is available on all
      patients 0.5 to 10 years (mean, 7.6+/-3.1 years). All patients are asymptomatic.
      Exercise test results on the three oldest patients were normal.
      Bradytachyarrhythmias developed in 4 patients (36%). Right ventricular to
      pulmonary artery conduit replacement was needed in 5 patients 2.2 to 7.1 years
      (mean 5.2+/-3.6 years) postoperatively. Mild to moderate tricuspid valve
      regurgitation persisted in 2 patients. Systemic left ventricular fractional
      shortening was 36% to 47% (mean, 39%+/-4.6%), and ejection fraction was 49% to
      70% (mean, 60.8%+/-7.9%). CONCLUSIONS: The double switch operation can be
      performed safely with minimal intermediate and long-term complications.

PMID- 11845881
TI  - Cytokine balance in infants undergoing cardiac operation.
AB  - BACKGROUND: The control of the systemic inflammatory response taking place during
      cardiac operations depends on adequate antiinflammatory reaction. In this
      prospective study we tested the hypothesis that cytokine balance during pediatric
      cardiac surgical procedures would be influenced by the patients' preoperative
      clinical condition, defined as hypoxemia or heart failure. METHODS: Twenty
      infants (median age, 8 months) with hypoxemia owing to intracardiac right-to-left
      shunt (group 1, n = 10) or with heart failure because of intracardiac left-to
      right shunt (group 2, n = 10), scheduled for elective primary corrective
      operation, were enrolled. Plasma levels of the proinflammatory cytokine
      interleukin (IL) 6, the natural antiinflammatory cytokine IL-10, and the markers
      of the acute-phase response, C-reactive protein and procalcitonin, were
      sequentially measured before, during, and after cardiac operation up to the 10th
      postoperative day. The ratio of IL-10 to IL-6 levels served as a marker for the
      individual's antiinflammatory cytokine balance. RESULTS: Group 1 showed higher
      preoperative IL-6 (p < 0.001), lower IL-10 levels (p < 0.02), and lower ratio of
      IL-10 to IL-6 levels (p < 0.001) than group 2. Preoperative C-reactive protein
      and procalcitonin were not detectable. In group 1, preoperative IL-6 levels
      inversely correlated with preoperative oxygen saturation (Spearman correlation
      coefficient, -0.74, p < 0.02). During cardiopulmonary bypass, IL-6 levels were
      higher, whereas IL-10 and ratio of IL-10 to IL-6 levels were lower in group 1
      than in group 2. In all patients, postoperative IL-6 levels were positively
      correlated with duration of inotropic support and serum creatinine value and
      inversely correlated with oxygenation index and diuresis. CONCLUSIONS: Infants
      with hypoxemia show a preoperative inflammatory state with low antiinflammatory
      cytokine balance in contrast to those with heart failure. This in turn is
      associated with lower perioperative antiinflammatory cytokine balance and might
      contribute to postoperative morbidity.

PMID- 11845882
TI  - Beta-receptor downregulation in congenital heart disease: a risk factor for
      complications after surgical repair?
AB  - BACKGROUND: Neurohormonal activation in children with heart failure due to
      congenital heart disease leads to downregulation of myocardial beta-receptors
      that may influence the postoperative course after cardiothoracic surgery.
      METHODS: Myocardial biopsies of 26 children (aged 14+/-4 months) were obtained
      from the right atrium during cardiac surgery. Patients were allocated to either
      of two groups based on the duration of their intensive care unit stay: group 1
      comprised those who stayed less than 7 days (n = 17), whereas group 2 comprised
      those who stayed more than 7 days, plus 3 infants who died during the early
      postoperative course (n = 9). For beta1- and beta2-mRNA quantitation, real-time
      polymerase chain reaction with fluorescence-labeled products was used. RESULTS:
      Values for myocardial beta1-receptor gene expression were twice as high in group
      1 children compared with group 2 (beta1-receptor 0.12+/-0.07 versus 0.06+/-0.03,
      p = 0.0016; beta2-receptor 0.12+/-0.07 versus 0.06+/-0.03, p = 0.0071). Beta
      receptor gene expression in 16 children who received standard treatment for heart
      failure averaged lower than in the 10 children who received additional
      propranolol. CONCLUSIONS: Beta-receptor downregulation due to congestive heart
      failure has an impact on the postoperative course in children with congenital
      disease and depends on heart failure therapy.

PMID- 11845883
TI  - Repair of congenital malformations of the mitral valve: early and midterm
      results.
AB  - BACKGROUND: The aims of this study were to determine early and midterm survival
      and freedom from reoperation, and to identify the predictors for poor
      postoperative outcome in children undergoing mitral valve (MV) repair owing to
      congenital malformations of the mitral valve. METHODS: Between January 1990 and
      February 2001, 94 consecutive children with congenital MV disease underwent valve
      repair. The mean age was 5.2+/-3.3 years (range 20 days to 15 years). Twenty-five
      (26.6%) children were less than 1 year old. Isolated MV disease was found in 21
      (22.4%) patients. MV stenosis was the predominant lesion in 21 (22.4%) patients
      with a mean left atrial to left ventricle diastolic peak gradient of 24.5+/-9.2
      mm Hg. MV regurgitation was the predominant pathophysiology in 73 (77.6%)
      patients with a mean regurgitation grade of 3.3+/-0.7. RESULTS: The hospital
      mortality was 8.5% (8 of 94). Three patients required permanent pacemaker
      implantation owing to complete atrioventricular block. Two patients underwent
      mediastinal exploration for significant bleeding. Postoperatively the
      echocardiography color Doppler study demonstrated a significantly lower mean end
      diastolic left atrium to left ventricle gradient 8.7+/-2.2 mm Hg (p < 0.001) in
      patients with MV stenosis and a mean regurgitation grade of 0.9+/-0.6 (p < 0.001)
      in patients with MV regurgitation. Actuarial survival and actuarial reoperation
      free survival were 89.2% and 76.3%, respectively. Multivariate analysis
      demonstrated that age less than 1 year (p = 0.035), hammock MV (p = 0.0093),
      cardiothoracic ratio greater than 0.6 (p < 0.0001), and associated cardiac
      anomalies (p = 0.003) were strong predictors for poor overall freedom from
      reoperation and midterm survival. CONCLUSIONS: Mitral valve repair for congenital
      mitral valve disease yields acceptable early and midterm mortality and
      reoperation rates. Strong predictors for poor overall freedom from reoperation
      and midterm survival were age less than 1 year, hammock MV, cardiothoracic ratio
      greater than 0.6, and associated cardiac anomalies.

PMID- 11845884
TI  - Mediastinal synovial sarcoma: report of two cases with molecular genetic
      analysis.
AB  - Synovial sarcoma occurs predominantly in the paraarticular regions of the
      extremities. Synovial sarcoma of the mediastinum is an exceedingly rare neoplasm
      that has overlapping histologic and immunophenotypic features with other tumors
      in the differential diagnosis. We describe two cases. One is a 67-year-old
      patient who presented with chest pain and shortness of breath. Diagnostic imaging
      revealed a mediastinal mass extending over the cardiac apex. Histopathology,
      immunohistochemistry, and molecular genetic analysis confirmed the diagnosis of
      synovial sarcoma. The patient underwent surgical resection and postoperative
      radiation therapy. He is alive and well 18 months after diagnosis. This case
      illustrates the importance of proper procurement of frozen tissue for molecular
      genetic analysis for the identification of the t(X;18), characteristic of
      synovial sarcoma. Detection of this translocation is of paramount importance to
      confirm this diagnosis, particularly when this neoplasm arises in atypical
      locations outside the extremities.

PMID- 11845885
TI  - Bilateral elastofibroma dorsi.
AB  - Elastofibroma dorsi was diagnosed in a 48-year-old woman with bilateral
      subscapular tumor masses diagnosed asynchronously in an interval of 4 months in
      spite of presence of another lesion at first admittance. She underwent subsequent
      resections of the lesions. They were diagnosed as elastofibroma. Reevaluation of
      the initial computerized tomography of thorax indicated an omitted small lesion
      with a 2-cm diameter and 25.2-day doubling time. Although the real neoplastic
      nature of elastofibroma is unknown, bilateral presence of the masses with
      different sizes and relatively short doubling times of the lesions must be kept
      in mind.

PMID- 11845886
TI  - Bronchial artery aneurysm disguised as a leiomyoma of the esophagus.
AB  - Bronchial artery aneurysm (BAA) is a rare entity with potentially fatal
      hemorrhagic complications. It is usually diagnosed using a computed tomography
      scan or angiography in emergency situations (clinical picture of aortic
      dissection or massive hemoptysis). We report a case of bronchial artery aneurysm
      where dysphagia was the predominant symptom. Thoracic computed tomography and
      endoscopic ultrasound seemed to indicate leiomyoma of the esophagus. The final
      diagnosis revealed a bronchial artery aneurysm.

PMID- 11845887
TI  - Preoperative diagnosis of a paraesophageal bronchogenic cyst using
      endosonography.
AB  - Preoperative diagnosis of paraesophageal bronchogenic cysts is difficult, and its
      management remains controversial. We describe the case of an incidental
      paraesophageal bronchogenic cyst, suspected preoperatively with endoscopic
      ultrasound and established intraoperatively by thoracoscopic inspection. Surgical
      treatment was achieved by cyst excision using a needlescopic technique.
      Endoscopic ultrasound seems to be the preoperative diagnostic test of choice for
      paraesophageal bronchogenic cysts.

PMID- 11845888
TI  - Transsternal transpericardial closure of a postlobectomy bronchopleural fistula.
AB  - We report a case of chronic empyema and bronchopleural fistula after lobectomy
      for tuberculosis. The patient had undergone four different surgical procedures to
      correct his bronchopleural fistula during an interval of seven years. Finally, he
      had a successful closure of the fistula using the transsternal transpericardial
      approach.

PMID- 11845889
TI  - Successful repair of an aortoesophageal fistula with aneurysm from esophageal
      diverticulum.
AB  - Aortoesophageal fistula is a rare, frequently fatal, cause of upper
      gastrointestinal bleeding, and there are few reported survivors of it. We report
      a successful surgical case of aortoesophageal fistula associated with an
      infective thoracic aortic aneurysm. The patient had been diagnosed as having an
      esophageal diverticulum 8 months before admission. The aortoesophageal fistula
      was completely resected, followed by esophagojejunum anastomosis and patch
      closure for the entry of the aneurysm and omental coverage to the wall of the
      descending aorta in one stage. In this case, esophageal diverticulum was
      diagnosed before the development of an aortoesophageal fistula associated with an
      aneurysm.

PMID- 11845890
TI  - Combined correction of an adult scimitar syndrome and coronary artery bypass
      grafting.
AB  - Combined scimitar syndrome and coronary artery disease is a rare combination of
      congenital and acquired cardiac disease in adults. Hence, no guidelines for
      surgical correction are available. We report on the case of a 60-year-old man
      with coronary artery disease and scimitar syndrome. The patient underwent
      arterial coronary revascularization and simultaneous correction of the scimitar
      syndrome utilizing a new surgical approach with a modified pericardium-baffle
      reconstruction of the anomalous right pulmonary vein.

PMID- 11845891
TI  - Aortic wall alterations after use of gelatin-resorcinol-formalin glue.
AB  - We report the case of a patient who underwent reoperation 8 years after aortic
      valve replacement because of aneurysmal dilatation of the aortic root. During the
      initial intervention, gelatin-resorcinol-formalin glue had been applied on the
      outside of the aortic root. Perioperative examination revealed a necrotic
      appearance of the right coronary sinus, with contained ruptures at two different
      sites. Histologic analysis showed major destruction of the aortic root media,
      leading to vascular wall thinning and rupture. The use of gelatin
      resorcinolformalin glue may expose patients to major alterations of the aortic
      wall.

PMID- 11845892
TI  - Composite graft replacement after aortic valvuloplasty in Takayasu arteritis.
AB  - A 24-year-old woman had undergone valvuloplasty of the aortic valve and external
      reinforcement of an aneurysm of the ascending aorta during the active phase of
      Takayasu arteritis 1 year prior to admission to our hospital. On examination, she
      was diagnosed as having a large false aneurysm of the ascending aorta with
      annuloaortic ectasia and severe aortic regurgitation, bilateral common carotid
      artery aneurysms with a left internal carotid artery saccular aneurysm, and
      bilateral subclavian artery and right vertebral artery obstructions due to
      Takayasu arteritis. Because of the risk of rupture, surgical intervention was
      carried out in spite of the fact that aortitis was in the active phase.

PMID- 11845893
TI  - Aortic root replacement with anomalous origin of the coronary arteries.
AB  - Coronary arteries with anomalous origin from the aorta can be at risk during
      aortic valve procedures. We report a case of origin of the circumflex and left
      coronary artery from the proximal right coronary artery in a patient with a
      bicuspid aortic valve and aortic root aneurysm. Attention to the anatomic
      relationship of the anomalous arteries to the aorta allowed safe aortic root
      replacement.

PMID- 11845895
TI  - Pseudoxanthoma elasticum: is the left internal mammary artery a suitable conduit
      for coronary artery bypass grafting?
AB  - Coronary artery revascularization remains a feasible and beneficial treatment for
      coronary artery disease in patients with pseudoxanthoma elasticum. Careful
      angiographic evaluation of the left internal mammary artery and coronary arteries
      is required in patients with pseudoxanthoma elasticum with suspected coronary
      artery disease. A nonstenosed left internal mammary artery at angiography may be
      used as a conduit for coronary artery revascularization; however, both the effect
      of harvest and anastomosis on the disease process in the left internal mammary
      artery and the long-term patency of left internal mammary artery grafts remain
      unknown.

PMID- 11845894
TI  - Reoperative transmyocardial laser revascularization for late recurrent angina.
AB  - Transmyocardial laser revascularization (TMR) reduces anginal class and is
      indicated for severely symptomatic patients who are not candidates for
      conventional revascularization. This report describes a 72-year-old man who
      presented 4 years following initially successful TMR with recurrent angina
      refractory to maximal medical management. Reoperative TMR was performed with
      substantial improvement in angina and functional class.

PMID- 11845896
TI  - Surgical treatment of coronary sinus orifice atresia with hypoplastic left heart
      syndrome after total cavo-pulmonary connection.
AB  - Atresia of the coronary sinus orifice is rare. We describe the surgical treatment
      of coronary orifice atresia in an infant with a persistent left superior vena
      cava after total cavo-pulmonary connection for hypoplastic left heart syndrome.
      The diagnosis was made by cardiac catheterization after total cavo-pulmonary
      connection at 8 months of age. After surgery, cardiac performance deteriorated.
      At reoperation, the coronary sinus was fenestrated to the left atrium. The
      patient survived surgical treatment of coronary sinus ostial atresia unroofed to
      the left atrium, guiding the placement of the fenestration with a probe placed
      through the open cardiac end of left superior vena cava.

PMID- 11845897
TI  - Repair of transposition of the great arteries with total anomalous pulmonary
      venous return.
AB  - A 13-year-old Haitian girl presented with complex congenital heart disease
      consisting of transposition of the great arteries with total anomalous venous
      return. The patient exhibited clinical findings of long-standing congestive heart
      failure and cyanosis. She underwent complete repair with resolution of her
      symptoms.

PMID- 11845898
TI  - Isolated left ventricular ischemia after the Norwood procedure.
AB  - Aortic atresia is the most severe variant of hypoplastic left heart syndrome
      (HLHS), and has been associated with significant mortality after stage I
      palliation. Coronary artery abnormalities are more prominent in this group of
      patients, especially in the presence of a patent mitral valve. Herein, we
      describe a case of isolated left ventricular ischemia after the Norwood procedure
      in a neonate with hypoplastic left heart syndrome, left ventricular hypertrophy,
      mitral stenosis, aortic atresia, and anomalous left coronary artery.

PMID- 11845899
TI  - Aortopulmonary window due to balloon angioplasty after arterial switch operation.
AB  - We report 2 cases of aortopulmonary window that developed after balloon
      angioplasty for pulmonary artery stenosis. Both patients had undergone arterial
      switch operations for complete transposition of the great arteries before the
      angioplasty. These aortopulmonary windows were repaired through elective
      operations. The clinical features, diagnosis, management, and proposed mechanisms
      of this complication are described.

PMID- 11845900
TI  - Modification of the radial procedure in a patient with partial atrioventricular
      septal defect.
AB  - We successfully cured atrial fibrillation while preserving internodal conduction
      in a patient with a partial atrioventricular septal defect. Because the anterior
      and middle internodal tracts are interrupted by the defect, the lower right
      atrial incision of either the maze or the radial procedure may interrupt the
      remaining posterior tract, resulting in internodal conduction block. We deleted
      the posterior septal incision from the radial procedure and replaced it with a
      right-side left atriotomy. The patient resumed normal sinus rhythm with
      significant contraction of the right and left atria. The preserved internodal
      pathway through the posterior interatrial septum was confirmed by
      electrophysiologic study.

PMID- 11845901
TI  - Pathologic findings in atrial musculature seven years after the intraatrial
      tunnel Fontan.
AB  - Surgical specimens of the atrial wall were microscopically investigated 7 years
      after total cavopulmonary connection. The intima of the morphologically right
      atrium was thicker in the part used for the high-pressured venous channel than in
      the other portion placed for the low-pressured atrial cavity supporting the
      systemic circulation. The number of myocardial cells was smaller, and the area of
      interstitial fibrosis was greater, in both circumstances, when compared with the
      normal right atrium.

PMID- 11845902
TI  - Malignant mesothelioma with osseous differentiation.

PMID- 11845903
TI  - Traumatic aortic arch injury.

PMID- 11845904
TI  - Enlargement of the aortic annulus using a double-patch technique: a safe and
      effective method.
AB  - We have tested a new method to enlarge the aortic annulus using a double-patch
      technique after the Manouguian principle. Our study included 14 patients who had
      no operative mortality and no complications; long-term follow-up was 13 years.
      The method prevented mitral insufficiency and operative bleeding at the aortic
      root.

PMID- 11845905
TI  - Open inferior vena caval anastomosis during bicaval heart transplantation.
AB  - Performing a precise inferior vena caval (IVC) anastomosis during bicaval
      orthotopic heart transplantation can sometimes be challenging because of crowding
      of the operative field by the venous cannula and tourniquet. We performed bicaval
      orthotopic heart transplantation in 10 patients using an open IVC anastomotic
      technique with vacuum-assisted venous drainage. A long venous cannula was passed
      into the IVC through the femoral vein. The IVC anastomosis was performed after
      removing the IVC tourniquet under vacuum-assisted venous drainage. A precise edge
      to-edge IVC anastomosis was successfully performed in all patients. This
      technique may result in greater anastomotic precision and improved outcomes.

PMID- 11845906
TI  - An alternative surgical approach to facilitate minimally invasive mitral valve
      surgery.
AB  - An alternative approach to minimally invasive mitral valve surgery is described
      that permits direct great vessel cannulation and direct aortic clamp occlusion
      through a 6- to 8-cm incision. This approach reduces the complexity of the
      procedure, and hopefully, will contribute to more widespread adoption of less
      invasive techniques in mitral valve surgery.

PMID- 11845907
TI  - Neuroendocrine carcinoma (carcinoid) of the thymus associated with Cushing's
      syndrome.
AB  - Neuroendocrine carcinoma (carcinoid) of the thymus associated with Cushing's
      syndrome is a rare disease. Recent evidence suggests that these tumors form part
      of a continuous spectrum ranging from well-differentiated carcinomas to small
      cell carcinomas. We report two new cases and review the 23 cases reported in the
      literature since 1972. The different diagnostic modalities are discussed, and an
      algorithm for the diagnosis of ectopic secretion of adrenocorticotropin (ACTH) is
      presented. In the future, the advent of radiologic and nuclear imaging as well as
      more accurate workup should help to diagnose these tumors at an earlier stage and
      improve the long-term outcome.

PMID- 11845908
TI  - Endothelial damage during myocardial preservation and storage.
AB  - Preservation and storage techniques represent two major issues in routine cardiac
      surgery and heart transplantation. Historically, these methods were conceived to
      prevent ischemic injury to myocardium after cardiac arrest during heart
      operations. Evidence shows that endothelium plays a critical role in the
      maintenance of normal heart function after cardiac operation, mainly by
      controlling the coronary circulation. Methods for preservation and storage,
      developed initially to protect cardiomyocyte function, may be deleterious for
      vascular endothelium and compromise myocardial protection. In this review article
      the present knowledge about endothelial injury secondary to preservation and
      storage techniques is discussed.

PMID- 11845909
TI  - Diaphragm pacing.

PMID- 11845910
TI  - Talc: isn't it safe?

PMID- 11845911
TI  - Left gastric to coronary artery bypass.

PMID- 11845912
TI  - Dilated aortic root and stentless valve implantation.

PMID- 11845913
TI  - Valved stentless composite graft 35.

PMID- 11845914
TI  - Cardiac valve replacement in patients on dialysis.

PMID- 11845915
TI  - The use of the Shelhigh porcine valve conduit in infants.

PMID- 11845916
TI  - Double-inlet left ventricle: successfully staged ventricular septation with 12.5
      years follow-up.

PMID- 11845917
TI  - Ave Sina was an Islamic physician.

PMID- 11845918
TI  - Cardiac hydatid cysts.

PMID- 11845919
TI  - Measuring consumer perceptions of quality differences among competing health
      benefit plans.
AB  - In this paper, we combine revealed preference and survey data on attribute
      importance to estimate parameters that represent average perceived differences in
      the quality and convenience of competing health benefit plans. We find that
      consumers do not perceive differences in provider quality across options. though
      they do perceive differences related to waiting time and access to specialists.
      In order to validate our approach, we estimate parameters representing perceived
      premiums and compare the estimates to actual premium differences. The results
      suggest that consumers correctly perceive the high-premium option to cost more
      than the low-premium option. These results increase our confidence in the use of
      stated importance data to identify and interpret parameters measuring the effect
      of otherwise unobservable attributes of choice alternatives.

PMID- 11845920
TI  - Youth tobacco control: reconciling theory and empirical evidence.
AB  - Youth smoking is an important target for public policy. The implicit assumption
      behind targeting youth is that policies that reduce youth smoking initiation will
      reduce lifetime smoking propensities. This assumption has never been tested
      empirically. I use data from the National Longitudinal Survey of Youth (NLSY) to
      follow the smoking pattern of one cohort of teenagers. I examine how smoking
      rates in youth and young adulthood are affected by the taxes individuals faced at
      age 14. In panel data analysis, I find that the effects of taxes at age 14 are
      considerably attenuated by adulthood. I find some evidence suggesting that this
      result is a consequence of delayed smoking initiation that is correlated with
      taxes. These results suggest that reducing smoking among teens through tax policy
      may not be sufficient to substantially reduce smoking in adulthood.

PMID- 11845921
TI  - On using sample selection methods in estimating the price elasticity of firms'
      demand for insurance.
AB  - We evaluate a technique based on sample selection models that has been used by
      health economists to estimate the price elasticity of firms' demand for
      insurance. We demonstrate that, this technique produces inflated estimates of the
      price elasticity. We show that alternative methods lead to valid estimates.

PMID- 11845922
TI  - Life-cycle preferences over consumption and health: a comment on Bleichrodt and
      Quiggin.
AB  - In a recent issue of the Journal of Health Economics, Bleichrodt and Quiggin
      (1999) developed a model of life-cycle preferences over consumption and health to
      analyze QALY-based decision making. This analysis is critically appraised
      concerning issues of QALY-maximization on an individual and on an aggregate level
      as well as of the role of death in QALY-models. It is concluded that a more
      general approach might be useful for the analysis of QALYs and life-cycle
      preferences over consumption and health.

PMID- 11845923
TI  - Defining the value of a statistical life: a comment.
AB  - In a recent paper [J. Hlth. Econom. 20 (2001) 131] Per-Olov Johansson claims to
      demonstrate that a commonly used intuitive definition of the value of a
      statistical life (VSL) is wrong, and that empirical estimates of VSLs are biased
      estimators of what he defines as the theoretically correct concept of the value
      of saving a life. In this comment I first argue in favor of a theoretically
      correct concept that is different from Johansson's because it incorporates the
      risk of death into the individual's lifetime budget constraint. I then show that
      the common intuitive definition of a VSL in fact is consistent with the
      theoretically correct concept and thus, provides an appropriate empirical basis
      for estimating the value to society of mortality-reducing projects.

PMID- 11845924
TI  - The impact of health plan report cards on managed care enrollment.
AB  - How does the release of health plan performance ratings influence employee health
      plan choice? A natural experiment at General Motors (GM) Corporation provides
      valuable evidence on this question. During the 1997 open enrollment period, GM
      disseminated a health plan report card for the first time. By comparing 1996 and
      1997 enrollment patterns, our analysis estimates the impact of the report card
      information while accounting for fixed, unobserved plan traits. Results indicate
      that employees are less likely to enroll in plans requiring relatively high out
      of-pocket contributions. Results with respect to report card ratings suggest that
      individuals avoid health plans with many below average ratings.

PMID- 11845925
TI  - Quality information and consumer health plan choices.
AB  - This paper presents an empirical analysis of the effects of providing information
      about plan quality on consumers' health plan choices in a private employment
      setting. Analysis of plan switching behavior suggests that the provision of
      quality information had a small, but significant effect on consumer plan choices.
      Employees were more likely to switch from plans with lower reported quality.
      Cross-sectional analyses of plan choice indicate that reported quality played a
      role in plan selection even after controlling for other health plan
      characteristics commonly associated with plan choice. The age of the policyholder
      and the type of policy purchased moderated the effects of plan characteristics on
      plan choice in ways that may be consequential for adverse selection.

PMID- 11845926
TI  - Employee demand for health insurance and employer health plan choices.
AB  - Although most private health insurance in US is employment-based, little is known
      about how employers choose health plans for their employees. In this paper, I
      examine the relationship between employee preferences for health insurance and
      the health plans offered by employers. I find evidence that employee
      characteristics affect the generosity of the health plans offered by employers
      and the likelihood that employers offer a choice of plans. Although the results
      suggest that employers do respond to employee preferences in choosing health
      benefits, the effects of worker characteristics on plan offerings are
      quantitatively small.

PMID- 11845927
TI  - Switching costs, price sensitivity and health plan choice.
AB  - We investigate the extent to which sensitivity to health plan premiums differs
      across individuals according to characteristics related to the cost of switching
      plans. Our results indicate substantial variation in price sensitivity related to
      expected health care costs: younger, healthier employees are between two and four
      times more sensitive to price than employees who are older and who have been
      recently hospitalized or diagnosed with cancer. We also find evidence of status
      quo bias: estimated premium elasticities are significantly higher for new hires
      than for incumbent employees. Simulations combining our results with actuarial
      data illustrate the cost implications of risk-related differences in price
      elasticity.

PMID- 11845928
TI  - Outdoor air pollution and emergency room visits at a hospital in Delhi.
AB  - Several reports from large metropolitan cities have indicated significant
      association between acute morbidity and mortality from cardio-respiratory
      disorders and daily levels of major pollutants in the ambient air. Despite the
      wide-spread public concern about the adverse health effects of air pollution,
      there is substantial uncertainty regarding the effects of these pollutants at a
      concentration typical of Delhi, which is one of the ten most polluted cities in
      the world and the most polluted city in India. This study was undertaken to
      correlate the daily levels of various pollutants with the number of patients
      visiting the All India Institute of Medical Sciences (AIIMS, New Delhi) casualty
      for aggravation of certain defined cardiorespiratory disorders. Daily counts of
      patients visiting the emergency room of the AIIMS for acute asthma, acute
      exacerbation of chronic obstructive airway disease (COAD) and acute coronary
      event was obtained in prospective manner from January 1997 to December 1998.
      Daily mean levels of ambient CO, NOx and SO2 were monitored along with
      temperature and humidity. Data was analysed using one day time lag for events of
      interest. Time series analysis was undertaken using Poisson regression and
      population averaged general estimation equation, correcting for auto-correlation,
      days of the weak and season. The ambient levels of pollutants exceeded the
      national air quality standards on most of the days, over the two year period.
      Further, emergency room visits for asthma, COAD and acute coronary events
      increased by 21.30%, 24.90% and 24.30% respectively on account of higher than
      acceptable levels of pollutants. It is concluded that there is considerable
      burden of cardiorespiratory diseases in Delhi due to high levels of ambient air
      pollution.

PMID- 11845929
TI  - Nitric oxide derivative in bronchoalveolar lavage fluid from patients with
      idiopathic pulmonary fibrosis.
AB  - Idiopathic pulmonary fibrosis is a chronic inflammatory disorder of unknown
      aetiology with a number of inflammatory cells playing a role in its pathogenesis.
      In this study, we have attempted to find out the possible role of nitric oxide in
      its pathogenesis by way of measuring the nitrite and nitrate levels in the
      bronchoalveolar lavage fluid. Ten patients of histologically proved idiopathic
      pulmonary fibrosis and 10 controls (5 with normal chest skiagrams and 5 with
      sarcoidosis) were included in the study Bronchoalveolar lavage was carried out in
      these cases. The levels of nitrates and nitrites were increased in cases of
      idiopathic pulmonary fibrosis (0.77+/- 0.36 and 8.93 +/- 2.63 nmol/mg of protein)
      compared to those in controls (0.38 +/- 0.06 and 3.80 +/- 1.11, respectively for
      sarcoidosis patients); (0.39 +/- 0.13 and 6.56 +/- 1.61 for subjects with normal
      chest skiagrams). These differences were statistically significant (p < 0.05 to
      0.01). These findings suggest a possible role of nitric oxide in the pathogenesis
      of idiopathic pulmonary fibrosis.

PMID- 11845930
TI  - Radiographic patterns in lung cancer.
AB  - Three hundred seventy three previously diagnosed patients with lung cancer,
      attending the Lung Cancer Clinic at this institute were studied. Chest
      radiographs were interpreted in all cases. Radiography was compared in different
      cell types. Squamous cell carcinoma 158 (42.4%), followed by small cell lung
      cancer 122 (32.7%), was the commonest histological subtype. Upper zone was
      involved in maximum number of cases 158 (42%), followed by mid zone 122 (32.7%),
      lower zone 60 (16%) and the entire lung 33(8.8%). Adenocarcinoma presented as a
      peripheral mass in 37 (61%) cases and in 23 (38.3%) as a central lesion.
      Presentation as a central mass (114, 72.2% cases) was more common among squamous
      cell carcinoma than as a peripheral lesion (44, 27.8% cases). Similarly, small
      cell cancer also presented more commonly as a central lesion (102, 83.6% cases)
      than as a peripheral lesion (20, 16.4% cases). Isolated pleural effusion was
      present in 3.8% in squamous cell lung cancer, 22% in adenocarcinoma and only 4%
      in small cell lung cancer.

PMID- 11845931
TI  - Lung transplantation: management and complications.
AB  - Lung transplantation has become an accepted treatment modality for end stage lung
      disease including emphysema, fibrosing alveolitis, cystic fibrosis, pulmonary
      hypertension and bronchiectasis. Despite the use of potent immunosuppressive
      drugs, acute rejection occurs frequently, especially in the first few weeks and
      months after transplantation. Bacterial, viral and fungal infections frequently
      occur in lung transplant recipients. Rapid diagnosis and adequate treatment of
      infections is needed. The side effects with the use of long term
      immunosuppressive agents includes renal toxicity, hypertension, neurotoxicity,
      hyperlipidemia, leucopoenia, hyperglycaemia, weight gain, osteoporosis and
      malignancy. However, obliterative bronchiolitis (OB) which is regarded as a
      chronic rejection process remains the dominant cause of morbidity and mortality
      in the long-term survivors of lung transplantation. This article focuses on the
      postoperative and long term management of lung transplant recipients.

PMID- 11845932
TI  - Right atrial thrombus and pulmonary thromboembolism.

PMID- 11845933
TI  - Vocal cord dysfunction presenting as refractory asthma.
AB  - Vocal cord dysfunction is a rare variety of upper airway obstruction
      characterized by typical laryngoscopic features and may mimic an acute asthma
      attack. The case presented in this report pertains to a 15-year-old girl who had
      repeated acute episodes of dyspnoea and wheezing and remained non-responsive to
      corticosteroids and inhaled bronchodilators requiring endotracheal intubations
      for adequate control. Laryngoscopic findings were consistent with vocal cord
      dysfunction. She was treated with a tracheostomy and psychological support.

PMID- 11845934
TI  - Bone marrow involvement in a primary mediastinal extragonadal non-seminomatous
      germ cell tumour.
AB  - A case of primary mediastinal extragonadal germ cell tumour with involvement of
      bone marrow, a rare finding, is reported with a review of literature.

PMID- 11845935
TI  - Congenital diaphragmatic hernia: delayed presentation with asymptomatic spleenic
      herniation.
AB  - Patients with congenital diaphragmatic hernia (CDH) usually present in the
      immediate neonatal period with respiratory distress. Presentation beyond the
      neonatal period has, however, been reported. We report a case of a 3-year-old
      child who presented with a six months history of respiratory symptoms and had
      been subjected to a variety of therapies like antibiotics, antitubercular
      medication and two attempts at putting an intercostal tube, as radiographs were
      suggestive of pleural effusion. This study highlights the importance of a high
      index of suspicion, relevance of thorough clinical examination and non-invasive
      diagnostic modalities along with an uncommon occurrence of asymptomatic spleenic
      herniation at such a later age. Spleenic herniation is rare outside neonatal
      period.

PMID- 11845936
TI  - Pneumomediastinum, pneumothorax and subcutaneous emphysema during radiotherapy in
      primary cavitating bronchogenic carcinoma.
AB  - An extremely rare case of cavitating large cell carcinoma lung is reported in a
      middle aged man who developed pneumomediastinum, pneumothorax and subcutaneous
      emphysema on thirteenth day of his tele cobalt radiotherapy to chest. Possible
      mechanisms of such complications during radiotherapy are also discussed.

PMID- 11845937
TI  - Air pollution and health.

PMID- 11845938
TI  - Results of a cooperative educational program to improve prostate pathology
      reports among patients undergoing radical prostatectomy.
AB  - The information contained in pathology reports of radical prostatectomy specimens
      is critically important to treating physicians for the selection of adjuvant
      therapy, the evaluation of therapy, estimating prognosis, and analyzing outcomes.
      This information is also important to patients and their families. The first
      phase of this study consisted of a retrospective chart review of 554 cases of
      radical prostatectomy (ICD-9-CM procedure code of 60.5) in New York State for the
      second six-month period of 1996. This review focused on ten elements (quality
      indicators): submission of a frozen section, location of the adenocarcinoma,
      proportion of specimen involved by adenocarcinoma, perineural involvement,
      vascular involvement, seminal vesicle status, periprostate fat status, number of
      nodes submitted, status of nodes, and PIN (prostate intra-epithelial neoplasia).
      The second phase of this project consisted of an educational feedback program
      involving the directors of pathology laboratories in all hospitals in New York
      State. A post-intervention review of the medical charts of all male Medicare
      patients discharged from New York State acute care hospitals with the ICD-9-CM
      procedure code of 60.5 (radical prostatectomy) was conducted for the six-month
      period February 1 through July 31, 1999. A total of 304 charts were reviewed.
      Performance on the ten indicators in the first phase of the study varied from
      14.8% (periprostate fat status) to 85.9% (seminal vesicle involvement).
      Performance for all hospitals was 50% for four quality indicators and less than
      70% for seven. Post-intervention improvements in performance occurred with nine
      of the ten quality indicators. These improvements ranged from 1.4% (status of
      lymph nodes submitted) to 23.9% (proportion of specimen involved by
      adenocarcinoma). The results of this study demonstrate that the issues identified
      in the baseline with radical prostatectomy pathology reports were amenable to a
      cooperative educational intervention.

PMID- 11845939
TI  - The influence of proximity of prenatal services on small-for-gestational-age
      birth.
AB  - Some studies suggest that prenatal services may decrease the risk of poor fetal
      growth for full-term infants, but have not examined the influence of the
      availability of community health and social services. The availability of
      prenatal services may have a stronger effect among women already at high risk of
      a small-for-gestational-age (SGA) birth. Singleton full-term (> or = 37 weeks
      gestation) California births for 1997-98 (n = 744,736) were geocoded to maternal
      Census tract of residence. Women were placed into one of three demographic risk
      groups utilizing combinations of maternal age, marital status, parity, and
      education. SGA was defined as birthweight less than the 10th percentile for
      gestational age. Locations of WIC sites, prenatal care providers, and perinatal
      outreach programs were geocoded. Multilevel logistic regression was used to model
      the influence of community health care services on SGA, adjusting for additional
      maternal and community factors. There was no association between SGA and
      community services available for either high- or low-risk women, in either
      unadjusted or adjusted models. The addition of maternal prenatal care utilization
      to models did not change the results. Maternal residence near prenatal services
      was not associated with SGA, regardless of demographic risk; other community
      factors may warrant consideration.

PMID- 11845940
TI  - A multimedia breast cancer education intervention for low-income Latinas.
AB  - This paper discusses the results from the field test of a multimedia health
      education intervention, designed to provide breast cancer education for low
      income Latinas. The purpose of the field test was to ascertain whether the
      intervention produced significant changes in breast cancer knowledge and
      attitude, and screening intentions. A total of 1,197 Latina women participated in
      the field study at six different sites. The majority of the participants were
      under 65 years of age, foreign-born with less than eight years of education and a
      weekly household income that fell in the lowest income quintile for 1998
      (<$350.00). Participants were randomly assigned to a control or intervention
      condition. The control group was interviewed about their breast cancer knowledge,
      attitude and mammography intentions prior to exposure to the intervention, and
      served as the baseline group. Women in the intervention group exhibited higher
      knowledge scores than the pretest group (Chi sq., p < .0001). Never-screened
      women exhibited the largest differences in knowledge scores relative to the
      baseline sample. The intervention also increased the likelihood of women seeking
      information about a mammogram.

PMID- 11845941
TI  - Lay explanations for Kentucky's "Coronary Valley".
AB  - Kentucky and its neighboring states have some of the highest coronary heart
      disease (CHD) mortality rates in the United States, leading researchers to
      nickname the region "Coronary Valley." Currently, little is known about factors
      that account for "Coronary Valley"; however, understanding lay perspectives on
      CHD risk factors may provide insights into this high prevalence of CHD and may
      guide prevention efforts. In December 1999, a statewide telephone survey was
      administered to a random sample of Kentucky residents to elicit lay explanations
      for the high rates of CHD. Standard protocol for descriptive statistics was
      undertaken. Respondents (N = 624) identified most of the biomedically
      acknowledged risk factors, with an overwhelming majority acknowledging that high
      rates of smoking and poor diets contribute to CHD. Older respondents and those
      who reported having heart disease were more likely than others to identify
      factors beyond their control, including stress and pollution (p < .0005 and p <
      .00 1, respectively). After controlling for the presence of heart disease, age
      differences remained significant only among those who reported no heart disease.
      Education had marginal significance (p = .027) on explanations for CHD, while
      gender, racial or ethnic background, and type of community residence had no
      significant effects. Since most Kentuckians are aware of traditional risk factors
      underlying CHD, prevention efforts should be directed at removing structural and
      information barriers to behavior change (e.g., by providing smoking cessation
      programs) rather than limiting prevention efforts to traditional health education
      approaches (i.e., increasing knowledge of CHD risk factors).

PMID- 11845942
TI  - Impact of improved treatments on perceptions about HIV and safer sex among inner
      city HIV-infected men and women.
AB  - Protease inhibitor combination therapies have significantly improved the health
      of many people with HIV/AIDS. Prior studies, consisting mainly of gay men, have
      indicated that these treatments have prompted reduced concern about HIV and an
      increase in high-risk behavior. This study assessed the impact of HIV treatment
      advances on HIV-infected individuals living in inner-city areas. A convenience
      sample was used (n = 196), consisting largely of heterosexual African-Americans
      and Hispanics. Almost the entire sample had heard of the latest HIV treatments,
      and 75% were currently on protease inhibitor regimens. One-third of the sample
      reported that AIDS was a less serious threat nowadays and that being HIV-positive
      was not a big deal. Fifteen percent of respondents believed that protease
      inhibitor combination therapies reduced the risk of HIV transmission, and 10%
      believed that these treatments reduced need for safer sex practices. As in
      previous studies of other populations, a significant percentage (23%) of
      respondents practiced safer sex less often since new HIV treatments arrived. HIV
      prevention programs need to focus more attention on HIV-infected individuals in
      inner city areas. Interventions for these individuals need to address changing
      attitudes and behaviors stemming from HIV treatment advances.

PMID- 11845943
TI  - Randomized controlled trial of the tolerability, safety, and efficacy of
      adapalene gel 0.1% and tretinoin microsphere gel 0.1% for the treatment of acne
      vulgaris.
AB  - A prior meta-analysis of 5 randomized controlled trials indicates that adapalene
      gel 0.1% is as effective as tretinoin gel 0.025% against acne and has greater
      tolerability. To determine the tolerability and efficacy of adapalene gel 0.1%
      versus tretinoin microsphere gel 0.1% in 168 patients with acne vulgaris, we
      conducted a 12-week, multicenter, randomized, controlled, investigator-masked,
      parallel-group design study. Efficacy variables included noninflammatory,
      inflammatory, and total lesion counts; global grade; and global assessment of
      improvement in acne severity. Skin tolerability variables included erythema,
      desquamation (scaling), dryness, pruritus, and stinging/burning. Our results
      showed that the efficacy of adapalene gel 0.1% was comparable to that of
      tretinoin microsphere gel, and both treatments had similar onset of action.
      Cutaneous tolerability was noted in both groups, with scores significantly better
      with adapalene gel 0.1% than with tretinoin microsphere gel 0.1%, and
      significantly fewer treatment-related adverse events were reported with adapalene
      gel 0.1%.

PMID- 11845945
TI  - Polarized light photography and videomicroscopy greatly enhance the capability of
      estimating the therapeuic response to a topical retinoid (adapalene) in acne
      vulgaris.
AB  - Assessment of improvement in acne lesions following treatment is often based on
      clinical evaluation and photographs. However, limitations are associated with
      this sublective evaluation, making it difficult to accurately review individual
      acne lesions and to observe early response to therapy. Conventional photographs
      do not allow us to visualize small lesions, and it can be difficult to
      differentiate inflammatory lesions as papules or small nodules. Our objective was
      to evaluate a new standardized method for tracking individual acne lesions based
      on photographs. The effect of adapalene gel 0.1% on both inflammatory and
      noninflammatory acne lesions was evaluated using this technique. Polarized light
      photography and videomicroscopy were used to record the evolution of acne lesions
      over a 16-week period in 5 volunteers with moderate acne vulgaris. During the
      first 4 weeks before treatment, acne lesions were evaluated on a 3-times weekly
      basis to establish a pattern of progression and determine the length of time to
      resolution. Sebum secretion rates were monitored using Sebutape adhesive patches
      applied to the forehead and both cheeks for 1 hour. After 4 weeks, adapalene gel
      0.1% was used once daily at bedtime for 8 weeks; polarized light photography,
      videomicroscopy, and assessment of sebum production followed treatment response.
      This treatment period was followed by a further 4-week phase, after which acne
      lesions and sebum secretion rates were evaluated. Our results showed that the new
      methodology was appropriate to track acne lesions and allowed an accurate and
      more oblective evaluation of individual lesions. Using this methodology
      demonstrated that adapalene gel 0.1% causes rapid resolution of inflammatory and
      noninflammatory lesions. The probability of clearing inflammatory and noninflamma
      tory lesions during the treatment period increased, and the probability of new
      lesions appearing decreased. Sebum secretion rates declined in patients while on
      study drug, returning to near pretreatment levels following therapy cessation.
      Using sophisticated photography and videomicroscopy every other day proved to be
      a valuable, noninvasive, and reliable method of following response to adapalene
      treatment in patients with moderate acne vulgaris.

PMID- 11845944
TI  - Randomized, controlled, bilateral (split-face) comparison trial of the
      tolerability and patient preference of adapalene gel 0.1% and tretinoin
      microsphere gel 0.1% for the treatment of acne vulgaris.
AB  - Poor patient compliance is one of the main reasons for treatment failure in acne.
      Our objective was to evaluate the tolerability and patient preference of
      adapalene gel 0.1% compared with tretinoin microsphere gel 0.1% using a
      randomized, controlled, investigator-masked, bilateral (split-face), 4-week
      comparative study of the 2 products when applied once daily in 40 patients. We
      found that adapalene produced less stinging/burning than tretinoin at weeks 1 and
      4 and, overall, more patients felt more skin irritation on the side of the face
      treated with tretinoin than on the side treated with adapalene (P<.05). At week
      4, a significantly greater number of patients preferred adapalene gel 0.1% to
      tretinoin microsphere gel 0.1% (72.5% vs 27.5%, respectively, P<.01).

PMID- 11845947
TI  - Adapalene gel 0.1% is effective and well tolerated in acne patients in a
      dermatology practice setting.
AB  - The US Food and Drug Administration has approved adapalene gel 0.1% for use in
      the treatment of acne vulgaris. The objective of our study was to evaluate the
      efficacy and tolerability of adapalene gel 0.1% in the treatment of acne vulgaris
      in a clinical practice. We used a 12-week, multicenter, open-label,
      noncomparative phase 4 study of adapalene gel 0.1%. The study involved
      approximately 600 dermatologists in the United States and included 2,545 healthy
      men and nonpregnant women older than 14 years who had mild or moderate acne
      vulgaris. Of the patients enrolled, 75% completed the study and most of them
      (89%) showed an improvement in their acne (clear of acne or marked, definite, or
      minimal improvement) from baseline. Most patients (69%) were satisfied or very
      satisfied with adapalene therapy, and most (80%) wished to continue treatment.
      Only 3.7% of patients enrolled reported treatment-related adverse events (n=94),
      the most common being skin irritation (2.2%). We conclude from this open-label
      trial in a dermatology practice setting that adapalene gel 0.1% was effective and
      well tolerated and had a favorable safety profile. Furthermore, compliance with
      once-daily application of adapalene was rated as high by 92% of patients who
      responded to a self-assessment questionnaire.

PMID- 11845946
TI  - Efficacy and tolerance of adapalene cream 0.1% compared with its cream vehicle
      for the treatment of acne vulgaris.
AB  - Adapalene gel 0.1% is approved for use in the treatment of acne vulgaris. A new
      cream formulation, adapalene cream 0.1%, has been developed. Our objective was to
      evaluate the efficacy and tolerability of adapalene cream 0.1% in comparison with
      its cream vehicle, applied once daily for 12 weeks to patients with facial acne
      vulgaris. We used a 12-week, multicenter, randomized, double-blind, vehicle
      controlled, comparative phase 3 study of adapalene cream 0.1% and cream vehicle.
      The study enrolled 237 patients (125 males and 112 females), aged 12 through 30
      years, with mild-to-moderate acne vulgaris. Adapalene cream 0.1% demonstrated
      superior efficacy compared with its cream vehicle. Significantly lower numbers of
      total inflammatory and noninflammatory lesion counts were observed at the end of
      the study period in patients using adapalene cream 0.1% as opposed to those using
      cream vehicle (P<.05 compared with baseline, for all 3 parameters). Adapalene
      cream 0.1% caused more cutaneous side effects than the cream vehicle, but these
      were tolerated in most patients. In summary, the results of this study indicate
      that adapalene cream 0.1% demonstrates superior efficacy over cream vehicle for
      the treatment of acne vulgaris. Adapalene cream 0.1% also has excellent
      tolerability and is associated with a low incidence of cutaneous adverse events.

PMID- 11845949
TI  - Adapalene gel 0.1%: effective and well tolerated in the topical treatment of acne
      vulgaris in Chinese patients.
AB  - Acne vulgaris is a common dermatologic disease in Asian populations, as well as
      in Caucasians. Our objective was to evaluate the safety and efficacy of adapalene
      gel 0.1% in comparison with tretinoin gel 0.025% in Chinese patients with acne
      vulgaris. We used an 8-week, multicenter, randomized, controlled, investigator
      masked, parallel group design study of adapalene gel 0.1% and tretinoin gel
      0.025% in 150 Chinese patients with mild-to-moderate acne vulgaris. Our results
      showed that adapalene gel 0.1% had efficacy equivalent to tretinoin gel 0.025%
      against acne lesions in Chinese patients, with a more acceptable tolerability
      profile.

PMID- 11845948
TI  - Adapalene gel 0.1% for topical treatment of acne vulgaris in African patients.
AB  - Acne vulgaris is a common dermatologic disease in African patients, as well as in
      Caucasians. Our report evaluates the safety and efficacy of adapalene gel 0.1% in
      African patients with acne vulgaris. We used a 12-week, 2-center, open-label,
      noncomparative study of adapalene gel 0.1% in 65 African patients with acne
      vulgaris to assess the drug's effect on hyperpigmented lesions in people with
      dark skin. The study demonstrated that the progressive and significant
      improvements in lesion counts and global acne grades produced by adapalene in
      African patients were paralleled by significant improvements in the degree of
      hyperpigmentation of acne lesions. During treatment with adapalene, less than 5%
      of patients reported moderate or severe skin irritation at any time during the
      study, and the incidence of skin oiliness decreased markedly. We conclude that
      adapalene gel 0.1% was well tolerated and highly effective in African patients
      with acne vulgaris and was found to reduce hyperpigmentation.

PMID- 11845950
TI  - Adapalene in clinical practice.

PMID- 11845951
TI  - The use of cleansers as therapeutic concomitants in various dermatologic
      disorders.
AB  - The choice of a mild cleansing agent is important in the adjunctive management of
      various skin conditions, such as atopic dermatitis, acne vulgaris, rosacea,
      photoaging, retinoid-induced irritant dermatitis, and sensitive skin. There are 3
      major categories of cleansing agents: soaps, synthetic detergents, and lipid-free
      cleansing agents. The irritancy potential of cleansing agents is a function of a
      number of factors, including the pH, type of surfactants, and amount of skin
      residue. Furthermore, the presence of humectants and emollients also can
      influence the overall mildness of a cleansing agent. Agents with slightly acidic
      or neutral pH, nonionic surfactants, and minimal skin residue may be preferable
      for people who are at increased risk for irritancy reactions.

PMID- 11845952
TI  - The use of therapeutic moisturizers in various dermatologic disorders.
AB  - Moisturizers can serve as important adjunctive therapeutic modalities for
      patients with various dermatologic disorders, including acne vulgaris, rosacea,
      retinoid-induced irritant dermatitis, atopic dermatitis, psoriasis, and the skin
      dryness that appears to occur with intrinsic and extrinsic aging. Therapeutic
      moisturizers, defined as those proven in clinical trials to be both compatible
      with topical therapies and biocompatible with the skin, not only improve the
      signs and symptoms of dry skin but also, as research has demonstrated, help
      maintain hydration and overall integrity of the stratum corneum. The type of
      humectants and emollients contained in a therapeutic moisturizer can affect the
      overall tolerability of the formulation. Dermatologists should recommend
      therapeutic moisturizers that are noncomedogenic, devoid of irritant ingredients,
      and compatible with many therapeutic regimens.

PMID- 11845953
TI  - The Denekamp diadems--a review of Julie's achievements.
AB  - Dr Julie Denekamp, DSc, PhD, BSc was present at a symposium held in her honour in
      Uppsala in February 2001. This article presents some biographical details and
      summarizes the main features of the scientific work for which she is known in
      radiobiology applied to cancer treatment, now called Translational Research.
      Topics include fractionation, proliferation in normal tissues as well as tumours,
      early versus late reactions, radiosensitizers, vascular attack in tumours,
      neutrons (and pions), radiosensitizers, radioprotectors, hyperthermia, research
      methodology, and theoretical modelling.

PMID- 11845954
TI  - Do no harm--normal tissue effects.
AB  - Radiation therapy confers enormous benefits that must be balanced against the
      possibilities for harm including late toxicity in normal tissues and radiation
      induced second malignancies. A small percentage of patients experience severe
      late complications. The question is, do these late sequelae occur randomly, or
      are they confined to individuals who are genetically predisposed to
      radiosensitivity. Experiments with knockout mice and with patients demonstrate
      that individuals heterozygous for a number of genes appear to be radiosensitive.
      If radiosensitive patients were identified prospectively by genetic analysis,
      they could be spared the trauma of late sequelae. Several large studies have
      shown a statistically significant excess of radiation-induced malignancies in
      radiotherapy patients. Most second cancers are carcinomas, developing in the
      lining cells of the body often remote from the treatment site. Radiation-induced
      sarcomas appear only in the heavily irradiated areas. These are small in number
      but appear with a very high relative risk.

PMID- 11845955
TI  - Measuring hypoxia in solid tumours--is there a gold standard?
AB  - Tumour hypoxia is known to be associated with aggressiveness and poor response to
      treatment, which has stimulated the development of several methods able to detect
      hypoxic tumours. To date, only one method, the oxygen microelectrode, has been
      used to provide pretreatment measures of tumour oxygenation that correlate with
      local control and disease-free survival. In an effort to validate new methods,
      comparisons have been made between the Eppendorf oxygen microelectrode, the comet
      assay, and hypoxia marker binding in tumours of patients undergoing curative
      treatment or palliative radiotherapy. These comparisons suggest that tumours with
      median oxygen tensions below 10 mmHg have relatively high hypoxic fractions as
      measured by the comet assay (> 0.20). The fraction of cells that binds
      pimonidazole, detected in cells obtained by fine-needle aspiration biopsy,
      correlates well with the hypoxic fraction measured using the comet assay.
      However, in general, hypoxic fractions measured by the comet assay and
      pimonidazole binding correlate only poorly with Eppendorf measurements performed
      for the same tumour. Factors that might be responsible for these differences, and
      problems associated with measuring the 'relevant' hypoxic population are
      discussed.

PMID- 11845956
TI  - Hypoxia and perfusion measurements in human tumors--initial experience with
      pimonidazole and IUdR.
AB  - We describe our preliminary studies on the development of methods to measure
      hypoxia in standard paraffin sections of human tumors. Three parameters were
      investigated. First, image analysis of tumor vascularity yielded the parameter
      diffusion limited fraction (DLF), which is the amount of tumor tissue greater
      than a fixed distance from the nearest blood vessel. Secondly, the amount of
      tumor tissue stained with antibodies against bound reduced products of the
      bioreductive marker pimonidazole was assessed. Finally, the fraction of blood
      vessels showing no surrounding tumor tissue labeled with lUdR, a cell kinetic
      marker, was measured. DLF and pimonidazole monitor primarily chronic hypoxia,
      while it is hypothesized that the IUdR-negative fraction monitors acute hypoxia.
      Feasibility was demonstrated in a series of 10 esophageal and 10 rectal tumors
      (no drug administration), 10 cervix tumors (pimonidazole) and 14 head and neck
      tumors (pimonidazole and lUdR). Significant differences between tumors were found
      for all parameters. DLF correlated significantly with the pimonidazole fraction
      when all images of all tumors were included, although mean values per tumor
      showed no correlation. The IUdR-negative fraction did not correlate with either
      of the other two parameters. We conclude that it is feasible to measure hypoxia
      related, and possibly perfusion-related, parameters on paraffin sections for
      predictive purposes, although each method needs further validation. Each
      parameter will be correlated with outcome in a larger study on head and neck
      tumors treated with surgery with or without postoperative radiotherapy.

PMID- 11845957
TI  - Clinical relevance of intermittent tumour blood flow.
AB  - One of the goals of translational cancer research is to understand basic
      'phenomena' so that tumour response to therapy can be improved. One such
      phenomenon is intermittent tumour blood flow. The impact of the transient hypoxia
      that results from decreased tumour blood flow is now beginning to be appreciated
      in preclinical systems, and also receiving some attention in clinical practise.
      Thus in this article we review the nature and frequency of microregional blood
      flow changes in preclinical and clinical tumours and examine the impact of those
      changes on response to both radiotherapy and chemotherapy. Additionally, the
      implications of non-constant blood flow for both the growth of the unperturbed
      tumour and the regrowth of surviving tumour clonogens during and after therapy
      are examined.

PMID- 11845958
TI  - Targeting hypoxia in head and neck cancer.
AB  - The idea of 'targeting' hypoxia stems from recognition of the fact that oxygen
      (or its lack) is central to the practice of radiation oncology. Targeting
      embraces the alternative goals of trying to overcome hypoxia on the one hand and
      trying to exploit it on the other. This presentation briefly reviews these two
      approaches with major emphasis on the latter.

PMID- 11845959
TI  - Normal tissue response to low doses of radiotherapy assessed by molecular markers
      -a study of skin in patients treated for prostate cancer.
AB  - The aim of this study was to evaluate normal tissue response by molecular markers
      to multifraction low doses of ionizing radiation, with the focus on changes in
      repopulation, estimated using Ki-67 as the proliferation marker, and on
      expressions of the p53 and p21 proteins, identified as key proteins in the DNA
      damage checkpoint. Repeated skin biopsies were taken from patients treated for
      prostate cancer with radiotherapy. The expressions of Ki-67, p53 and p21 of the
      keratinocytes in the basal cell layer of the epidermis were quantified
      immunohistochemically. The dose to the basal layer was 1.1 Gy per fraction, given
      five times per week for seven weeks. The indices of the three markers were
      determined over the whole period. A significant suppression of the Ki-67 index
      was observed during the first weeks, followed by a significant gradual increase
      in the Ki-67 index over the last weeks. The p53 and p21 protein levels were
      almost zero in the unirradiated skin. Upon irradiation, both the p53 and p21
      index increased in a pattern very congruent to the Ki-67 index. In conclusion,
      daily fractions of about 1 Gy to the skin resulted in, for the keratinocytes in
      the basal layer, a cell growth arrest for a couple of weeks and a subsequent
      acceleration in repopulation during the following weeks of irradiation. The
      present findings also provided novel insights into the role of the p53/p21
      pathway in the response of a normal epithelium to ionizing radiation as it is
      applied in radiotherapy.

PMID- 11845960
TI  - Radiation nephropathy--the link between functional damage and vascular mediated
      inflammatory and thrombotic changes.
AB  - The extent of radiation-induced nephropathy, which develops progressively over
      periods of months to years after treatment, is strongly influenced by both total
      dose and dose per fraction. In this study we examined the relationship between
      the early expression of various thrombotic and inflammatory markers of
      endothelial cell (EC) damage in irradiated mouse kidneys and the subsequent
      development of nephropathy. Decreased levels of glomerular ADPase and increased
      levels of glomerular Vwf were seen from 4 or 20 weeks after irradiation,
      respectively. These pro-thrombotic changes were associated with increased
      fibrin/fibrinogen deposits, indicative of microthrombus formation, at later
      times. These events were, however, not sensitive to changes in total dose or dose
      per fraction, therefore they cannot be quantitatively linked to the development
      of radiation nephropathy. Increased leucocyte invasion of the renal cortex was
      also seen after irradiation; this was quantitatively dependent on both total dose
      and dose per fraction. Linear quadratic analysis of the leucocyte dose-response
      curves yielded an alpha/beta ratio of 7.7 Gy, which is significantly greater than
      the alpha/beta ratio or 2.7 Gy determined for nephropathy, indicating less
      fractionation sensitivity for the inflammatory response. We conclude that
      inflammatory changes contribute to, but do not entirely explain, radiation
      nephropathy. The role of thrombotic changes is less clear.

PMID- 11845961
TI  - Preoperative radiotherapy for rectal cancer--is 5 x 5 Gy a good or a bad
      schedule?
AB  - Preoperative radiotherapy substantially lowers local failure rates after rectal
      cancer surgery, an effect that is seen whether surgery is optimized, total
      mesorectal excision (TME), or not. Preoperative radiotherapy also slightly
      improves survival. Postoperative radiotherapy also decreases local recurrence
      rates, but the relative reduction is less pronounced even when higher doses are
      used. Preoperatively, a high-dose, short-term schedule, 5 x 5 Gy in one week, has
      been used in several randomised trials. This is a convenient schedule and has low
      toxicity if properly conducted. In trials where the radiation technique has been
      simplified, resulting in large irradiated volumes, unacceptable acute and late
      toxicities have been seen. It has not yet been possible to detect any late
      toxicity in trials where the treatment was given using techniques avoiding the
      irradiation of unnecessarily large tissue volumes outside the target volume. The
      relative advantages of using this short-term schedule relative to a conventional
      irradiation for about 5 weeks are discussed.

PMID- 11845962
TI  - The case against apoptosis.
AB  - Apoptosis is not as dominant a process in cell loss from normal tissues and
      tumours as has sometimes been claimed. The term 'programmed cell death', which
      many authors regard as synonymous with apoptosis, is an unsatisfactory term that
      is best avoided. In studies on the response of tumours to drug and radiation
      treatment, the use of apoptosis assays concentrates attention on the first decade
      of cell killing (0-90%), whereas the outcome of treatment depends on multi-log
      cell kill; an assay of clonogenic cell survival is the appropriate method for
      this purpose. Loss of colony-forming ability is the key event in treated tumour
      cells, and the appearance of morphological and molecular evidence of apoptosis is
      probably downstream from this event. Published studies that have compared
      apoptosis and cell survival responses in tumour cells have generally failed to
      find a causal relationship.

PMID- 11845963
TI  - Non-targeted radiation effects in radiotherapy--roles of radiation-induced
      genomic instability and of the bystander effect in cancer cure by radiotherapy.
AB  - Local tumour control by radiotherapy requires the complete sterilization of all
      tumour 'stem' cells in the tumour volume. Neither bystander effect nor radiation
      induced genomic instability is able to contribute substantially to the
      probability of local tumour control of the primary cancer by radiotherapy.
      However, the progeny of these surviving tumour 'stem' cells are likely to suffer
      from radiation-induced genomic instability, which results in the persistent
      appearance of non-stem cells, i.e. a reduced probability of self-maintenance.
      This results in a slower growth rate of the recurrent tumour, a reduced stem-cell
      fraction and, as a consequence, an increased radiosensitivity of the recurrent
      tumour. In some recurrent tumours, particularly those that develop very late and
      grow very slowly, radiosensitivity may be further increased by increased
      intrinsic radiosensitivity, which could be related to the as yet poorly defined
      phenotype of 'small colony formation'.

PMID- 11845964
TI  - Tumour stem cells--the evidence and the ambiguity.
AB  - Progressive growth of malignant tumours, metastatic spread and local recurrence
      after treatment can only be explained by the presence of cells with unlimited
      proliferative ability. While this is generally accepted, the proportion of such
      cells and their organization in a hierarchical system of stem cells and non-stem
      cell progeny is still a matter of controversy. Results of quantitative
      transplantation and dose requirement of curative radiotherapy have indicated low
      stem cell fractions in human and early passage rodent tumours, but uncertainty is
      introduced by uncontrollable experimental or biological factors and the
      probabilistic nature of stem cell performance itself Studies using a particular
      mouse carcinoma (AT17) have given direct insight into the number and clonal
      expansion of stem cells in situ, strongly supporting the hierarchical concept.
      The implications are important and concern the relevance of predictive assays,
      possible mechanisms of accelerated repopulation, or the role of adjuvant
      treatment strategies.

PMID- 11845965
TI  - A new look at proliferation.
AB  - Assessment of proliferation has failed to make an impact on clinical
      radiotherapy. In this review, a different view of proliferation, its organization
      and its implication for radiotherapy are presented. Cell kinetic heterogeneity is
      present in all tumours and understanding and measuring this heterogeneity might
      reveal insight and tools to predict the mode of failure and repopulation during
      different schedules of radiotherapy and chemotherapy.

PMID- 11845966
TI  - Translational Research--a new entity?
AB  - The term 'Translational Research' has been increasingly used during the past
      decade. Julie Denekamp defines the term as 'involved with the detailed assessment
      of the factors influencing tumour specificity of action in order to achieve the
      successful implementation of a laboratory concept into a clinical protocol'.
      Translational research needs laboratory and clinical research units with
      dedicated staff who can work together. Only the careful planning and performance
      of clinical trials gathering all the data that may relate to the response of
      tumour and to that of normal tissues will allow advances in knowledge and lead to
      improvement in the care of patients with cancer.

PMID- 11845967
TI  - Integrating health services for frail elderly people.

PMID- 11845968
TI  - Common guidelines and equitable service: variation between adjacent districts
      regarding admissions to elderly care institutions.
AB  - With the increasing number of older people, the cost of providing institutional
      care has become a major issue. In 1993 the introduction of care management and a
      needs-led approach aimed to remove the existing 'perverse incentive' to
      institutional care and to ensure equality in the dependency levels of those who
      were admitted to care. To test this consistency, we examined the dependency
      levels of all persons aged > or = 65 years admitted to residential and nursing
      homes in two adjacent Health and Social Services (HSS) Community Trusts in
      Belfast, Northern Ireland, in the year following the introduction of care
      management. We measured differences between the Trusts with respect to number of
      admissions, levels of dependency as determined by several standard scoring
      systems, financial support, source of admission and demographic information. A
      total of 389 people were surveyed. Trust A had significantly higher levels of
      physical dependency and mental impairment in both residential and nursing homes
      than Trust B. We also identified differences in dependency with respect to
      funding status, with those who were self-funding in Trust B having lower physical
      dependency in residential and nursing homes and less mental impairment in nursing
      homes than supplemented residents. This study reports the existence of variations
      between adjacent Community Trusts operating under the same policy guidelines with
      respect to the dependency levels of admissions to residential and nursing care.
      These differences may relate to number of places available, the economic status
      of the population, and the assessment procedures of the two Community Trusts. The
      need for standard assessment and eligibility criteria is highlighted.

PMID- 11845969
TI  - Emergency hospitalization in the elderly in a French university hospital: medical
      and social conditions and crisis factors precipitating admissions and outcome at
      discharge.
AB  - Emergency admissions of elderly patients constitute a major management issue due
      to the complexity of their problems. The aim of this retrospective observational
      study was to identify medical and social characteristics and crisis factors for
      emergency department (ED) hospitalization in elderly patients, and to evaluate
      the influence of these factors on the length of stay and outcome at discharge.
      During a 4-month period, 396 patients aged 70 years and older were referred to
      the ED of a University Hospital (Hjpital Edouard Herriot) in Lyon, France. A
      questionnaire specifically designed for the study was completed for each patient
      using the information in the patients' files previously filled in by the "Rapid
      Geriatric Assessment Team" of the ED. We described civil and marital status,
      living conditions, reason for admission to ED and other associated pathologies
      according to the ICM-9, crisis factors, length of stay (LOS) and outcome at
      discharge. The mean age was 81.9 years (SD 6.5); two thirds (66.7%) of the study
      subjects were female, and 46.7% were widowed; the majority (68.7%) lived in their
      own homes. The main reasons for admission were cardiopulmonary diseases in 31.6%
      of cases, followed by neuropsychiatric disorders in 28.2%, and falls in 8.3%; a
      final category (31.8%) included subjects admitted for general, non-specific
      symptoms. Among the crisis factors observed, 49.4% presented an acute episode of
      a chronic illness, 33.6% lived alone, and 20.9% had been hospitalized during the
      6-month period preceding the study. The average LOS was 3.15 days. The
      multivariate model showed that falls increase LOS by 74%, dementia by 65%, and
      depression by 21%. Upon discharge, 13% returned to their residence before
      hospitalization, 55% were transferred to a medical speciality ward, and 4% to
      other facilities, whereas only 19% were transferred to a geriatric ward, and 9%
      died during their stay in the ED. The multinomial model showed that outcome at
      discharge was influenced by functional dependency, dementia, depression, and
      acute episodes of a chronic illness. For many elderly, the ED remains a critical
      point of access to more complete managed care. This elderly population is
      comprised of polypathological, frail persons whose morbid state requires
      multidisciplinary management in geriatric units. The findings of this study
      suggest that interventions of multidisciplinary networks, such as home health
      care programs aimed at detecting crisis factors and establishing early prevention
      of crisis states, may improve unfavorable medical and social conditions and
      reduce hospitalization in geriatric patients.

PMID- 11845970
TI  - In-hospital referral source and rehabilitation outcome of elderly stroke
      patients.
AB  - To date, there is no data regarding the association of patient in-hospital
      referral source and stroke rehabilitation outcomes. The objective of the present
      study was to investigate the possible relation between in-hospital referring
      source, whether directly from an emergency ward (EW) or indirectly through a
      general medical ward (GMW), and the functional outcomes achieved during
      rehabilitation of such stroke patients. This retrospective observational study
      included 315 consecutive patients, admitted for rehabilitation following the
      onset of acute stroke. We compared those referred directly to us from the EW,
      with others referred from GMWs. Functional status was assessed by Functional
      Independence Measure method (FIM). Functional outcome was determined by total FIM
      gain (efficacy) and daily FIM gain (efficiency), both absolute and relative (to
      potential). The two study groups were similar in terms of age, gender, and
      diagnosis. FIM admission scores were higher at admission in patients admitted
      directly from the EW, compared with those referred from GMWs (72.5 +/- 27.5 and
      62.7 +/- 25.6, respectively) but similar at discharge (77.4 +/- 28.8 and 80.7 +/-
      32.5, respectively). Length of stay (LOS) in the GMW group was longer as compared
      to the EW group. Efficacy was significantly associated with being married,
      younger age, hemiplegia, and admission scores between 40-60. Both absolute and
      relative efficacy and efficiency rates of rehabilitation were significantly lower
      among patients referred from the EW. We conclude that in-hospital referral source
      is associated with different rehabilitation outcomes in stroke patients. Direct
      admission of stroke patients from the EW is associated with lower rehabilitation
      efficacy and efficiency rates, compared with those admitted from GMWs. The
      findings support the implementation of different selection methods, underscoring
      the need of both clinicians and administrators to consider the in-hospital
      referral source as a potential factor associated with stroke rehabilitation
      outcome.

PMID- 11845971
TI  - Homocysteine and life-style in the elderly.
AB  - Elevated homocysteine increases the risk of vascular diseases but little
      information is available about this issue in the elderly. The aim of this cross
      sectional study was to evaluate the relationships between homocysteinemia and
      gender, anthropometric, and life-style characteristics in a community-dwelling
      elderly population (65 men and 120 women; 67-78 years). Basal plasma homocysteine
      levels were determined by High Performance Liquid Chromatography (HPLC). Clinical
      records, and nutritional and anthropometric variables were collected in all
      subjects. Body composition was evaluated in all subjects by Dual energy X-ray
      Absorptiometry (DXA). Thirty-three percent of women and 66% of men had hyper
      homocysteinemia. In women, a positive correlation was present between
      homocysteinemia, age, diastolic blood pressure and plasmatic creatinine, and a
      negative correlation between homocysteine, fiber intake and folates. In males,
      there was a positive correlation between plasma homocysteine, age, and body mass
      index. Multiple regression analysis showed that fat-free mass, cigarette smoking,
      fiber intake, vitamin B6 and total kcal intake accounted for 18% of homocysteine
      variance in males (R2 = 0.18, p<0.05). Significantly higher homocysteine values
      were found in women with a history of cardiovascular disease than in those
      without (16.6 +/- 9.4 vs 13.8 +/- 4.4 micromol/L, p<0.05). Homocysteinemia was
      significantly higher in elderly men compared to women (16.7 +/- 4.7 vs 15.3 +/-
      7.6; p<0.05). Gender differences in homocysteine disappeared after adjusting for
      fat-free mass. This study confirms the age-related increase in plasma
      homocysteine. Life-style characteristics seem to influence significantly
      homocysteine levels in the elderly. Our study shows that gender effects on
      homocysteine may be attributed to differences in body composition.

PMID- 11845972
TI  - The prevalence and psychosocial characteristics of the frail elderly in Japan: a
      community-based study.
AB  - There is insufficient epidemiological data about frail elders in Japan. Few
      studies concerning the relationship between psychosocial characteristics and
      frailty exist in the literature. The purpose of this study was to assess the
      prevalence and to explore the characteristics of the frail elderly in a community
      of Japan by cross-sectional and case-control studies. Data were collected from a
      total of 2,310 non-institutionalized persons aged 65 years or older, by mail
      survey and interview. We defined frailty as a precursor of disability. The
      prevalence of frail elders was estimated at 6.1%. After controlling for age and
      gender, multiple logistic regression analyses disclosed that frail elders
      displayed significantly higher emotional reliance on another person, worsening
      self-efficacy, fair or poor subjective health, and poor functional ability than
      independent elders, and significantly higher self-efficacy than bedridden elders.
      The most noticeable finding in this study was the significant association of
      psychosocial factors with frailty among the community-dwelling elderly. Based on
      our study results, we suggest that when controlling physical variables,
      psychosocial variables might strongly affect the frail status among elderly
      persons.

PMID- 11845973
TI  - A pattern of long-term predictors of health ratings among older people.
AB  - The aim of our study was to examine the predictors of health ratings by applying
      a path analysis model to a set of data from 75-year-old men and women in a 5-year
      follow-up study. The study was part of the Evergreen project with the study group
      comprising all the eligible inhabitants of Jyvaskyla, central Finland (N=382).
      The data were based on an interview and study center examinations focusing on
      different domains of health and functional capacity. Among the women, better
      health ratings at baseline, better functional ability and maximal working
      capacity, and a higher number of social contacts were important direct predictors
      of better health ratings at follow-up. Among the men, better health ratings at
      baseline, and depending on the model, higher physical activity or a lower number
      of chronic conditions and better functional ability were the most important
      direct predictors. The explanatory power of the path analysis models was 31-39%
      for men and 32% for women. In conclusion, health ratings reflect multiple
      dimensions of health and functioning. In addition to significant direct effects
      on health ratings, the predictors also have sequential effects running from life
      style through functional performance and the activities of daily living to health
      ratings. The factors associated with health ratings differ to some extent by
      gender.

PMID- 11845974
TI  - Summarizing amount of difficulty in ADLs: a refined characterization of
      disability. Results from the women's health and aging study.
AB  - Activities of Daily Living (ADLs) rating scales often classify older persons as
      independent or dependent in self-care activities. However, with this type of
      classification system little information is available on people who, while not
      dependent, do report some difficulty in performing self-care activities. This 3
      year prospective cohort study presents an ADL summary scale that assesses a
      gradient of difficulty in ADLs for moderately to severely disabled women aged 65
      and older living in the Baltimore, Maryland area. At baseline and for each of six
      interviews done at 6-month intervals, an ADL summary score measuring ADL
      difficulty was created. ADL summary score slopes were created for each woman who
      completed at least the baseline and first three follow-up interviews. The
      baseline ADL summary score and slope of the ADL summary score were used to
      predict risk of future hospitalization, nursing home admission and death.
      Additionally, 6-month ADL summary change scores were calculated in order to
      assess change in the ADL summary score for women who did and did not report an
      acute event (MI, stroke or hip fracture) at follow-up. The ADL summary scale
      showed excellent reliability. Intraclass correlation coefficients ranged from
      0.83 to 0.93 for measures made one week apart. The 6-month average correlation
      coefficient was 0.77. The ADL summary scale also performed well in tests of
      validity. Poorer scores on the ADL summary scale were significantly and inversely
      related to an objective physical performance scale. The baseline ADL summary
      score and slope of the ADL summary score predicted future risk of
      hospitalization, nursing home admission and death. Each unit increase in the
      slope of the ADL summary score was associated with a 19% (95% CI 1.10, 1.29)
      increased risk of hospitalization, a 57% (95% CI 1.37, 1.81) increased risk of
      nursing home admission and a 41% (95% CI 1.22, 1.64) increased risk of death,
      adjusting for potential confounders. The mean 6-month ADL change score for women
      reporting an acute event (2.59) was significantly different from those not
      reporting an acute event (0.52). The strongest and most significant mean 6-month
      ADL change score was observed for women who reported a hip fracture (4.52)
      followed by stroke (2.40) and MI (1.00). These results demonstrate that the ADL
      summary scale presented has validity, reliability and is sensitive to change.
      This scale, therefore, offers the opportunity to classify functional problems in
      a larger proportion of the population than do ADL dependence scales.
      Additionally, it gives us a way to identify earlier functional changes, and a way
      to track the natural history of functional problems as well as a response to
      interventions.

PMID- 11845975
TI  - The pupillary light reflex in aging and Alzheimer's disease.
AB  - The pupillary light reflex is reported to be reduced in amplitude in Alzheimer's
      disease (AD). The purpose of this study was to determine whether this effect is
      measurable under conditions typical of clinical rather than laboratory settings.
      A head-mounted infra-red videopupillometer was used to measure the amplitude of
      pupillary constriction in 12 patients with probable AD, 12 healthy age-matched
      older adults and 12 young adults. The constriction to the onset of bright light
      relative to the resting amplitude was significantly reduced in AD compared with
      both control groups. This result is consistent with an acetylcholine-related
      deficit in AD and supports the findings of Prettyman et al. and Fotiou et al. The
      impairment is likely to be caused by degeneration in relays in the midbrain but
      cholinergic deficits in the peripheral parasympathetic pathway cannot be
      excluded. The variation in pupillary response between individuals may preclude
      its use for diagnostic purposes. However, if the changes in pupillary response in
      AD are related to change in neurotransmitter status, then the value of such a
      technique may be in its use in providing an objective, non-invasive monitor of
      physiological abnormality with which to follow disease progression and treatment
      efficacy.

PMID- 11845976
TI  - Cancers connected with mutations in RET proto-oncogene.
AB  - Germline mutations of RET proto-oncogene are connected with inherited cancer
      syndrome multiple endocrine neoplasia type 2. The syndrome is characterized by
      incidence of medullary thyroid carcinoma frequently associated with
      pheochromocytoma and hyperparathyroidism. Genetic testing of family members at
      risk significantly contributed to diagnosis and management of MEN 2. Early
      genetic screening for RET mutations allow to detect people who have inherited the
      MEN2 specific RET mutation with subsequent possibility to of prophylactic
      thyroidectomy. On the other hand those family members at risk of MEN 2 who had
      not inherited the mutation do not require further testing. The involvement of RET
      proto-oncogene in tumorigenesis is reviewed.

PMID- 11845977
TI  - Cysteine proteinases in tumor cell growth and apoptosis.
AB  - During their evolution tumor cells acquire and mobilize various mechanisms that
      crucially affect their capability of proliferation, invasiveness and metastasis.
      Recent findings provide evidence that tumor cell associated cysteine proteinases
      such as some lysosomal cathepsins and apoptotic caspases are fundamentally
      involved in specific developmental traits of tumor cell populations. Tumor cell
      exterior-associated cysteine cathepsins B and L promote tumor growth, invasion
      and metastasis through degradation of extracellular connective matrices and
      through endothelial cell growth-directed activities. On the other hand, caspases 
      3, -7 and -6, generated in tumor cell cytoplasm via a robust activation of their
      zymogens, suppress tumor cell growth, invasion and metastasis through proteolytic
      devitalizing and remodeling of tumor cells into readily phagocytable apoptotic
      corpses. Tumor cell variants that are deficient in expression of effector caspase
      zymogens or are capable to suppress the extrinsic and intrinsic activation
      mechanisms of effector caspase zymogens and the activity of effector caspases
      have a significant survival advantage in environments of various death stimuli.
      Advancements in pharmacological targeting of tumor associated pathogenic
      lysosomal cysteine cathepsins and in apoptotic caspases-oriented conditioning of
      tumor cells may substantially contribute to therapeutic control of tumor
      diseases.

PMID- 11845979
TI  - Potentiated antitumor effects of interleukin 12 and interferon alpha against
      B16F10 melanoma in mice.
AB  - Systemic administration of cytokines has not found broad application in cancer
      immunotherapy due to its toxicity and lack of effectiveness in a broad spectrum
      of tumors. Among the most promising cytokines used often in pre-clinical and
      clinical trials are interferon alpha and interleukin 12. We have shown in our
      study that combining IL-12 with IFN-alpha in a dose which alone does not show
      antitumor activity results in potentiated antitumor effects without inducing
      toxicity.

PMID- 11845978
TI  - Flow cytometry of peripheral blood and bone marrow cells from patients with hairy
      cell leukemia: phenotype of hairy cells, lymphocyte subsets and detection of
      minimal residual disease after treatment.
AB  - By flow cytometry (FC) and an extensive panel of markers we characterized
      leukemia cells from the peripheral blood (PB) and bone marrow (BM) of 13
      symptomatic patients with hairy cell leukemia (HCL). Hairy cells (HCs) identified
      in the large cell gate always expressed B-cell markers - CD19, CD20, CD22, HLA
      DR, and 'HCL-restricted' markers - CD22+CD11c, CD25 and CD103. Other markers, not
      followed regularly, were occasionally expressed, such as CD34, CD38, CD71, CD15,
      CD10 and kappa/lambda light chains. Furthermore, in one patient with suspect but
      not proved HCL in PB or BM, neither morphologically nor immunologically, we
      confirmed the diagnosis of HCL. Only the immunophenotyping of splenic cells after
      splenectomy confirmed HCL diagnosis. Flow cytometry was repeated at 3-5 month
      intervals, after treatment with 2-Chlorodeoxyadenosine (CdA) or less frequently
      alpha-interferon (IFN). We investigated serially lymphocyte subsets after
      treatment and we found profound and persistent CD4+ lymphopenia in majority of
      studied patients after CdA treatment. Simultaneously we investigated the value of
      FC to detect minimal residual disease (MRD) and to establish, whether MRD+ could
      predict relapse. Detection of MRD in our series predicted hematological relapse
      only in one case with persistent MRD+, in majority of cases with occasionally
      found MRD+ phenotype, did not. Using quantitative immunophenotyping we observed
      significantly higher values of molecule numbers of hairy cell B-cell markers,
      comparing to B-cells in nonleukemic gate of the same sample. Our study showed 1)
      the diagnostic value of FC in management of HCL patients, 2) long-lasting
      response in the majority of patients after CdA, 3) a profound and persistent CD4+
      lymphopenia in CdA treated patients, 4) some correlation between persistent MRD
      staining and hematological relapse, and 5) further, till now not described
      activated feature of HCs, given by the increased values of molecular numbers
      (molecules of equivalent soluble fluoresceine - MESF) in B-cell antigens of HCL.

PMID- 11845980
TI  - Comparison of methods used to study cell death in an adherent tumoral cell line
      with moderate clonogenic radiosensitivity.
AB  - Our objective was to compare different methods for studying programmed cell death
      in adherent H460 non-small lung cancer cells of moderate clonogenic
      radiosensitivity. The major effect of gamma-radiation was found to be the release
      of cells from the substratum. The different methods gave complementary and
      unexpected information: a) with the TUNEL method, a few non-apoptotic cells were
      found in the culture medium; b) with the flow cytometry after propidium iodide
      labeling, some hypodiploid cells which remained attached to the substratum were
      apoptotic, as demonstrated by the effect of a caspase inhibitor; c) with the
      annexin V labeling, the detached cells were demonstrated either necrotic or very
      late apoptotic; d) the mitochondria transmembrane potential (deltapsim),
      measurements demonstrated that the mitochondria were implicated in cell death
      induced by gamma-radiation. These data illustrate the need to use several
      complementary methods in the study of apoptosis in adherent cells exposed to
      gamma-radiation.

PMID- 11845981
TI  - AgNOR pattern and PCNA analysis in fine needle biopsies of liver cell carcinoma.
AB  - The aim of this study was to evaluate the prognostic and diagnostic value of
      AgNOR and PCNA staining mainly in fine needle biopsies of 34 liver cell
      carcinomas using an image analyzing system. The AgNOR number per nucleus and the
      relative AgNOR area, but not the PCNA index, showed a significant correlation
      with the histological tumor grade according to the classical and the modified
      Edmondson-Steiner's classification. Regarding univariate survival, only the grade
      of the classical Edmondson-Steiner's classification was of prognostic
      significance. The parameters sex, age, maximum tumor diameter, mean AgNOR number,
      total nuclear area and relative AgNOR area, nuclear area, PCNA index or the grade
      of the modified Edmondson-Steiner's classification did not reach statistical
      significance regarding survival. By a factor analysis, two factors could be
      created, which could explain together 72% of the variance of all parameters
      included in the study. In a linear discriminant analysis, the AgNOR variables
      could separate between normal liver cells and cells from high grade or low grade
      carcinomas in 83.7% of the cases. Therefore, we think that the AgNOR technique
      can be usefully applied in needle biopsies of liver carcinomas for the
      differential diagnosis and tumor grading.

PMID- 11845982
TI  - Comparison of two different methods for CD34+ selection and T cell depletion in
      peripheral blood stem cell grafts--our experiences with CellPro, E rosetting and
      CliniMACS technique.
AB  - The aim of this study was to establish a suitable method for in vitro T cell
      depletion in peripheral blood stem cell grafts for mismatched/haploidentical
      transplantation in children and adults with severe hematological disorders and
      for autologous transplantation in patients with autoimmune diseases refractory to
      conventional immunosuppressive treatment. Two different selection techniques have
      been used: CD34+ selection using immunoaffinity columns (CellPro Ceprate)
      followed by T cell depletion by E-rosetting or CD34+ selection using
      submicroscopic paramagnetic beads (CliniMACS device) with T cell depletion in a
      one step procedure. The mean purity and recovery of CD34+ cells and efficiency of
      T cell removal in the final product were compared. From March 1995 to December
      1998 we prepared twelve allografts using Cell Pro system for eight children with
      high-risk hematological malignancies and six autografts for six patients with
      severe autoimmune diseases. From January 1999 to October 2000 we prepared fifteen
      allografts using CliniMACS system for ten children with high-risk hematological
      diseases and inborn metabolic disorders or primary immunodeficiences, five
      allografts for three adult patients with high-risk hematological malignancies and
      two autografts for two patients with autoimmune diseases. In allogeneic
      transplantation the median purity of CD34+ cells in the final products after
      CellPro and E-rosetting was 85.6% (55.3%-95.7%); median recovery was 24.8% (17%
      35%), median transplanted doses of T cells per kilogram of body weight were
      0.66x10(4) (0-2.8); in autologous transplantation the median purity of CD34+ was
      92.6% (55.6%-96%), median recovery was 28% (22%-46.2%), median transplanted doses
      of T cells per kilogram of body weight were 0.39x10(4) (0.0-3.6). After CliniMACS
      technique the median purity of CD34+ cells was 94.87% (69.15%
      99%),medianrecoverywas 58% (30%-79.6%), median transplanted doses of T cells per
      kg of body weight were 0.254x10(4) (0-14.15); in autologous transplantation the
      median purity of CD34+ was 94% (94%-94%, median recovery was 97.4% (95%-99.8%),
      median transplanted doses of T cells per kilogram of body weight were 0.87x10(4)
      (0.49-1.24). We consider both methods of CD34+ selection and T cell depletion
      suitable for peripheral blood stem cell processing before mismatched hemopoietic
      stem cell transplantation in patients without identical donor or before
      autologous transplantation for severe autoimmune diseases. However, magnetic
      separation using CliniMACS system results in higher levels of purity and recovery
      with efficient T cell depletion.

PMID- 11845983
TI  - Conditioned medium from HeLa cells enhances motility of human monocyte-derived
      dendritic cells but abrogates their maturation and endocytic activity.
AB  - Progressive tumor proliferation may be associated with suppression of the immune
      response. Several different mechanisms can contribute to immune evasion. It is
      generally proposed that inhibition of dendritic cell functions would be a key
      mechanism by which tumors could escape immune surveillance. Therefore, the
      purpose of this study was to evaluate the capacity of HeLa cells conditioned
      medium (HeLa-CM) to modulate phenotypic and functional parameters of human
      peripheral blood monocyte-derived dendritic cells (DCs). Two types of reference
      DCs population were generated in vitro, the first cultured in the presence of IL
      4 and GM-CSF which represented immature DCs (iDCs) and the second, representing
      mature DCs (mDCs), was raised from the iDCs by additional stimulation with a
      maturation cocktail - TNF-alpha, IL-1beta, IL-6, PGE2. In parallel, the iDCs were
      treated with HeLa-CM collected from the tumor cells. The analysis of DC
      populations demonstrated that the HeLa-CM prevented maturation of these cells and
      also impaired their capacity to uptake an antigen and stimulate proliferation of
      allogeneic T cells. In contrast, HeLa-CM modulated DCs exhibited a 3-fold
      increase mobility over iDCs. The latter functional capacity did not correlate
      with the levels of matrix metalloproteinase expression in the analysed cells.
      Altogether, our results provide evidence that HeLa cells produce soluble factors
      that might dramatically alter basic phenotypic and functional characteristics of
      DCs.

PMID- 11845984
TI  - Leukemic transformation of polycythemia vera after treatment with hydroxyurea
      with abnormalities of chromosome 17.
AB  - The leukemogenic risk attributed to therapy of polycythemia vera with
      radiophosphorus and alkylating drugs has led, over the last 20 years, to the
      increased use of myelosupressive nonmutagenic drugs, especially hydroxyurea. But
      there exist reports, which showed the development of polycythemia vera into acute
      leukemia not only in patients treated with alkylating agents and radiophosphorus
      but also with single hydroxyurea. In this article we present two cases of
      polycythemia vera, in which the development to acute myeloblastic leukemia
      occurred after long-term treatment with hydroxyurea. Significant is the fact,
      that in both presented cases cytogenetic and FISH analysis showed abnormalities
      of chromosome 17, in the one of case fullfilled criteria for "17p-syndrome". Due
      to the possibility of leukemogenic potential in the time of hydroxyurea
      treatment, it is necessary to be careful especially in young patients. The
      dynamic follow up of cytogenetic analysis is necessary, especially, in those,
      where long-term hydroxyurea therapy is supposed.

PMID- 11845985
TI  - P-glycoprotein expression in adult acute myeloid leukemia: correlation with
      induction treatment outcome.
AB  - Drug resistance has become a major cause of the treatment failure in patients
      with acute leukemia. P-glycoprotein (P-gp), which is associated with multidrug
      resistance (MDR) phenotype, has been reported to be an important predictor of the
      treatment outcome. The aim of this study was to analyze the value of P-gp
      expression in bone marrow cells as a predictor of the response to remission
      induction chemotherapy, as well as duration of remission in adult patients with
      newly diagnosed acute myeloid leukemia (AML). We examined the expression of P-gp
      in 31 patients using the monoclonal antibody UIC2. Direct immunofluorescent
      labeling was performed and samples were analyzed by flow cytomery. Kolmogorov
      Smirnov test (D-value) was used to estimate UIC2 staining. A D > or = 0.3 for
      labeling of gated leukaemic blasts as compared to that of the isotypic control
      was defined positive (+) and compared to clinical data. P-gp expression was found
      in 14/31 (45.6%) patients, 17/31 (54.8%) of the samples were found P-gp negative(
      ). No correlation was found regarding age, sex and FAB subtype, altough 6/14
      (43%) cases with more than 50% of cells having P-gp expression, were CD34+/CD7+.
      Complete remission rates were significantly lower in UIC2+ patients than in UIC2-
      cases (70% vs 35%, p < 0.01). Complete remission duration was also shorter in
      UIC2+ patients (6 vs 12.4 months). Our data indicate, that P-gp expression is a
      reliable marker of resistance to induction treatment in patients with de novo AML
      and can help to identify patients who may require alternative regimens designed
      to overcome therapy resistance.

PMID- 11845986
TI  - Human glioma cells expressing herpes simplex virus thymidine kinase gene treated
      with acyclovir, ganciclovir and bromovinyldeoxyuridine. Evaluation of their
      activity in vitro and in nude mice.
AB  - Human glioma cell lines 8-MG-BA and 42-MG-BA were infected with retrovirus vector
      containing the herpes simplex virus thymidine kinase (HSVtk) gene. The effect of
      acyclovir (ACV), ganciclovir (GCV), and bromovinyldeoxyuridine (BVDU) on both,
      parental and HSVtk expressing glioma cells was studied in vitro. BVDU displayed
      the most potent cytotoxic properties in HSVtk-containing cells, however bystander
      killing of nontransduced parental cells in a mixture with HSVtk-containing cells
      was less potent, than observed for ACV or GCV. Taking into account the cytotoxic
      effect of different prodrugs used, as well as their ability to kill nontransduced
      bystander cells, ganciclovir was shown to be the most effective. Therefore the
      effect of GCV treatment on 8-MG-BA xenografts inoculated with PA-317JH5cl13 virus
      producer cells was further studied on nude mice.

PMID- 11845987
TI  - Polymorphism of the p53 gene within the codon 72 in lung cancer patients.
AB  - We tested the codon 72 single nucleotide polymorphism (SNP) of the tumor
      suppressor gene p53 for association with lung cancer. In our hospital-based case
      control study, 168 lung cancer patients (134 males and 34 females) and 148
      controls without malignant diseases were recruited. The genotype characteristics
      were determined by PCR-based RFLP method using DNA extracted from peripheral
      blood. Only in lung cancer patients but not in the controls we found both
      significant decrease of A1 allele of the p53 codon 72 (p=0.024, OR 0.56, 95% CI
      0.43-0.72) and A1/A1 homozygous genotype (p=0.006, OR 0.27,95% CI 0.15-0.51). The
      results of this study suggest a protective effect of A1 allele against lung
      cancer.

PMID- 11845988
TI  - Inhibition of RNA synthesis in vitro and cell growth by anthracycline
      antibiotics.
AB  - New derivatives of doxorubicin and daunorubicin with amidine group bonded to
      daunosamine at C-3' atom and bearing the morpholine ring attached to the amidine
      group have been recently synthesized. Their cytotoxic activities and effects on
      RNA synthesis in vitro were assayed. The drug concentrations inhibiting mouse
      leukaemia L1210 cell growth to 50% were about two- and three fold higher for the
      derivatives compared to doxorubicin and daunorubicin respectively. Inhibition of
      phage T7 RNA polymerase by the non-covalently interacting derivatives was also
      slightly lower than that by the parent compounds. As doxorubicin and
      daunorubicin, their amidine derivatives in the presence of dithiothreitol and
      Fe(III) ions are activated and covalently bind to DNA. The adducts formed affect
      RNA polymerase activity. Several bands corresponding to prematurely terminated
      RNA chains are observed by means of polyacrylamide gel electrophoresis. The
      patterns of bands are virtually identical for all the anthracyclines studied here
      and are similar to the terminations induced by actinomycin D. This observation is
      consistent with a notion that the adducts are formed at guanine in GpC sequences
      which are also binding sites of actinomycin D. A substantial difference between
      daunorubicin and its amidine derivative is shown by means of high performance
      liquid chromatography. The derivative undergoes rapid rearrangements in the
      presence of dithiothreitol and Fe(III) ions, while daunorubicin is stable for
      several hours under these conditions. The results presented here indicate that
      the amidine derivatives despite bulky morpholine substitution exhibit biological
      activity in the systems used here.

PMID- 11845989
TI  - Androgen sensitivity related proteins in hormone-sensitive and hormone
      insensitive prostate cancer cell lines treated by androgen antagonist
      bicalutamide.
AB  - Members of the bcl-2 gene family and endogenous inhibitors of cyclin-dependent
      kinases participate in the regulation of apoptosis and cell cycle in a diverse
      range of cell types and are implicated in the development of hormone refractory
      prostate cancer and resistance to anti-cancer therapy. The expression of several
      of these genes can be regulated by steroid hormones and related agents via their
      nuclear receptors. However, insufficient information considering the protein
      expression after the treatment by hormone antagonists is available. The aim of
      this study was to evaluate the expression of anti- and pro-apoptotic proteins,
      (Bcl-2, Bax), and to correlate this with the appearance of some nuclear receptors
      and cell cycle related proteins in androgen sensitive and androgen insensitive
      prostate cancer cell lines, LNCaP and DU-145, after the treatment by androgen
      antagonist bicalutamide. Our results revealed that androgen receptor (AR)
      expression in LNCaP cells decreased, however in DU-145 cells AR slightly
      increased following anti-androgen treatment. The same agent stimulated expression
      of p21Waf1/Cip5 and p27Kip1 in LNCaP, as well as in DU-145 cell lines. Bcl-2
      level increased slightly in LNCaP cells and, in DU-145 cells was almost
      undetectable. Bax expression was not changed in LNCaP but significantly decreased
      in DU-145 cells. Similarly, retinoid X receptor beta (RXRbeta) level was
      significantly down regulated after 24 hours in DU-145 and also in LNCaP cells
      after 72 hours. These results confirm that androgen withdrawal therapy employing
      anti-androgens may elicit different signalling pathways in various types of
      prostate cancer that may be dependent on AR status and AR sensitivity.

PMID- 11845990
TI  - Threshold-based fitting methods for non-linear (WDRC) hearing instruments-
      comparison of acoustic characteristics.
AB  - Six threshold-based prescriptive methods for non-linear hearing instruments were
      compared for a standard audiogram and three simulated listening situations. Six
      hearing aids were programmed according to the manufacturers' recommended initial
      fittings for the specified audiogram. Coupler gain measurements were then made
      with speech-like signals, and loudness and speech intelligibility index (SII)
      were calculated. Large differences between estimated insertion gain-frequency
      responses were seen. These differences resulted in large differences in
      calculated loudness, whereas the SII calculations showed only small differences
      between the fitting methods. For two of the methods, DSL[i/o] and FIG6. a
      comparison between the original prescriptions and the hearing aid manufacturers'
      implementations of the prescriptions was made. The results showed large
      differences between prescribed and implemented gain.

PMID- 11845991
TI  - Bilateral hearing aids--effects and consequences from a user perspective.
AB  - The present study assesses the experiences with bilateral amplification in a
      group of 144 people provided with two hearing aids between May 1994 and July
      1997. Two-thirds of the participants preferred to use both prescribed hearing
      aids. The participants reported that they used their hearing aids frequently.
      Bilateral amplification was appreciated especially for recognizing speech, for
      sound localization and for superior sound quality. Situations in which the
      subjects showed the highest appreciation of two hearing aids were when attending
      lectures and theatre performances and for communication in noisy background
      situations. There were statistically significant differences between users of
      bilateral and unilateral hearing aids regarding judgement of sound quality of
      hearing aid processed signals and localization ability in favour of bilateral
      hearing aid amplification. The self-assessed advantages of bilateral
      amplification demonstrated in this study should motivate a generous prescription
      strategy of two hearing aids.

PMID- 11845992
TI  - Age and noise-induced hearing loss.
AB  - The purpose of the study was to evaluate the effect of noise, age and confounders
      in noise-induced hearing loss (NIHL). Information about work exposure, the use of
      hearing protective devices, audiogram, environmental and biological factors was
      collected from 406 paper mill workers exposed to noise levels of 91-94 dB(A), 124
      forest workers exposed to noise levels of 96-99 dB(A) and 176 shipyard workers
      exposed to noise levels 95-97 dB(A). In addition to noise exposure, we collected
      the following confounders: smoking habits, serum cholesterol, systolic or
      diastolic blood pressure and use of analgesics. Subjects were classified based on
      median values, into high- and low-risk groups. The confounders were a significant
      source of hearing loss (HL) in younger and elderly groups of subjects, serum
      cholesterol level being the most important. In risk analysis the confounders
      partly masked the effects of noise in the development of HL. For subjects with
      less than two confounders, occupational noise exposure determined the development
      of NIHL. As the number of confounders increased, the noise exposure was overruled
      by these factors in the development of HL. In analysis where the subjects were
      matched with pairs by age, exposure, blood pressure and serum cholesterol level,
      the elderly subjects were more susceptible to NIHL than younger subjects. Factors
      independently but causally related to age were important in the development of
      NIHL among workers exposed to noise levels below 98 dB(A).

PMID- 11845993
TI  - Two families with phenotypically different hereditary low frequency hearing
      impairment: longitudinal data and linkage analysis.
AB  - Two families with low frequency hearing impairment have been described
      previously. Family A (Danish) presented a sensorineural hearing impairment most
      pronounced for frequencies below 2 kHz and a pedigree typical for an autosomal
      dominant trait with complete penetrance (Konigsmark type). Family B, originating
      from the Faroe Islands, showed conflicting audiological test results, making a
      valid classification impossible. The pedigree suggested autosomal dominant
      inheritance with incomplete penetrance. The objectives of the present study are
      to acquire longitudinal audiometric data, to clarify the mode of transmission,
      and to localize the mutant gene by reevaluation of the two families. The methods
      used are evaluation of the family history, audiological examination and linkage
      analysis. In family A, update of the pedigree fitted the assumption of an
      autosomal dominant mode of transmission. In six examined subjects audiological
      data were available from the previous study. The median progression over a 13-21
      year period was 13.8 dB HL for the thresholds, averaged across 0.5, 1, 2 and 4
      kHz and 17.5 dB HL for the thresholds, averaged across 2 and 4kHz. In family B,
      the probable mode of transmission is autosomal dominant with reduced penetrance.
      In this family no progression of the hearing impairment was found. Linkage
      analysis of family A showed a lod score of 3.53, indicating significant linkage
      to the loci DFNA6 and DFNA14 on chromosome 4, previously found to be involved in
      low frequency hearing impairment. Family B was not linked to the region on
      chromosome 4, further adding to the genetic heterogeneity in low frequency
      sensorineural hearing impairment.

PMID- 11845994
TI  - Vision and hearing in old age.
AB  - The concomitant occurrence of hearing and visual impairment was investigated as
      part of an epidemiological longitudinal study of elderly people. An age cohort.
      originally consisting of 973 elderly people, was examined with visual and hearing
      tests three times at ages 70, 81-82 and 88. The best-corrected visual acuity was
      assessed. The hearing was measured by pure-tone audiometry and whispered and
      spoken voice (WSV). At age 70 there was no co-existence of visual and hearing
      impairments, and about 70% had normal vision and hearing. At 81-82 years 3-6%
      (WSV and audiometry. respectively) had low vision (VA < or = 0.3) and moderate to
      severe hearing loss, and more than one-tenth had normal vision and hearing. At 88
      years 8-13% had low vision and moderate to severe hearing loss, and none of the
      men and less than one-tenth of the women had normal vision and hearing. At age 88
      three times as many women as men had the combination of low vision and normal
      hearing. Normal vision with the combination of moderate to severe hearing loss
      was more often found in 88-year-old men. Mild impairments of the two senses were
      found in 0.5% at age 70 in 22%, 11% (WSV, audiometry) at age 81-82 and in 23%, 9%
      at age 88 years. At age 70 there was a statistical correlation between visual
      acuity and hearing measured with pure-tone audiometry in the male group. Those
      men with better hearing had slightly better visual capacity than those with
      hearing loss. No correlations were found for women at age 70 nor for women and
      men at ages 81-82 and 88. Ophthalmologists and audiology physicians should
      cooperate closely in the rehabilitation process to reduce disability and improve
      function and wellbeing among the oldest old.

PMID- 11845995
TI  - H1 and H2 histamine receptors mediate the production of inositol phosphates but
      not cAMP in human breast epithelial cells.
AB  - OBJECTIVE: In the present work we studied the H1 and H2 histamine receptor
      expression and function in HBL-100 and MCF-10A cells, derived from non
      tumorigenic human breast epithelia, and in MCF-10T, the H-ras-transfected MCF-10A
      counterpart. The signal transduction pathways associated with these receptors,
      and the expression of proto-oncogenes c-fos, c-myc and c-jun at the mRNA and
      protein levels, were examined. RESULTS: Saturation analysis using intact cells,
      showed two binding sites for [3H]tiotidine and [3H]mepyramine. Pretreatment of
      purified membrane with guanosine 5'-ythiotriphosphate resulted in the loss of the
      low affinity component for [3H]tiotidine binding, and of the high affinity
      component for [3H]mepyramine. In both cases, there was no modification in the
      total number of sites for both ligands. Neither H1 nor H2 agonists stimulated
      cyclic AMP production, though this pathway is functional in these cells. On the
      other hand, both H1 and H2 agonists enhanced phosphoinositide turnover in a dose
      dependent fashion, and this induction is pertussis toxin-insensitive. H1 and H2
      agonists did not influence the expression of c-myc or c-fos mRNA, nor their
      encoded proteins. CONCLUSIONS: These results indicate that the three cell lines
      examined showed functional H1 and H2 histamine receptors, which are involved in
      the metabolic turnover of inositol phosphates but are ineffective in the
      modulation of the cyclic AMP response. The fact that H2 receptors have lost their
      ability to stimulate cyclic AMP production would imply the loss of a regulatory
      mechanism of cell growth.

PMID- 11845996
TI  - Reduction in vesicant-induced cellular inflammation and hyperalgesia by local
      injection of corticotropin releasing factor in rabbit eyelid.
AB  - OBJECTIVE AND DESIGN: This study tested the ability of corticotropin releasing
      factor (CRF) to mitigate inflammatory cell infiltration and hyperalgesia after a
      direct subcutaneous doxorubicin injection, a vesicant drug that causes localized
      inflammation at the site of subcutaneous exposure. SUBJECTS: This study used 62
      adult New Zealand white rabbits. METHODS: Doxorubicin (1-2 mg), followed by
      either CRF (300, 150, 75, 35, 20 or 10 microg in 1 ml saline) or saline only, was
      injected into pairs of rabbit eyelids. One set of doxorubicin and CRF treated
      eyelid pairs also received injection of a CRF antagonist into one eyelid. The
      eyelid tissue was assayed from 1-7 days later for morphometric changes in CD11b
      positive inflammatory cell infiltrate. Hyperalgesia was assessed using the blink
      response to von Frey hair stimulation. Epidermal and dermal nerve fibers were
      visualized immunochemically using an antibody to PGP 9.5. The cellular
      localization of corticotropin releasing factor was determined
      immunohistochemically in eyelid tissue. RESULTS: Doses of CRF from 35 to 150
      microg significantly reduced inflammatory cell infiltration at all the post
      injury time intervals examined, from 2 h post-injection up until 7 days. Doses of
      10 and 20 microg CRF had no effect on local tissue inflammation caused by
      subcutaneous doxorubicin exposure. Doses of 35-150 microg CRF treatment
      significantly reduced the development of doxorubicin-induced hyperalgesia; this
      was maintained up to 4 days. Local CRF injections of 35-150 microg markedly
      reduced the doxorubicin induction of PGP-positive axons within the epidermis and
      subepidermis. CRF receptors were localized to the basal layer of the epithelium
      and to the subcutaneous nerve afferents. CONCLUSIONS: Local injection of CRF,
      after a subcutaneous exposure to the vesicant drug doxorubicin, significantly
      reduced the infiltration of CD11b-positive cells and reduced doxorubicin-induced
      hyperalgesia in the treated eyelids. This reduction in hyperalgesia appears to be
      a local peripheral effect, reducing nerve fibers within the subepidermal
      treatment area. This demonstrates the potential clinical usefulness of CRF
      because it could be used post-injury as a locally injected treatment; this potent
      local anti-inflammatory agent may have wide applications following drug,
      chemical, physical or surgical injury.

PMID- 11845997
TI  - A lipid A analog ONO-4007 induces tolerance to plasma leakage in mice.
AB  - OBJECTIVE: The effects of pretreatment with ONO-4007, a lipid A analog, on
      cutaneous plasma leakage induced by ONO-4007, lipopolysaccharide (LPS) and
      inflammatory mediators were investigated. MATERIAL: Male ddY strain mice.
      TREATMENT: Mice were pretreated with ONO-4007 (up to 6 mg/kg i.p.), 0-24 h prior
      to plasma leakage study. METHODS: Plasma extravasation was determined by dye
      leakage. RESULTS: Systemic ONO-4007 (6 mg/kg i. p.) pretreatment for 2 to 12 h
      inhibited plasma extravasation in the mouse skin elicited by ONO-4007 and LPS.
      The inhibition was dose-dependent. Plasma leakage induced by platelet-activating
      factor (PAF), histamine and 5-hydroxytryptamine (5-HT) was also inhibited by ONO
      4007 pretreatment. Plasma corticosterone levels increased 2 and 4 h after
      systemic ONO-4007 (6 mg/kg) administration and returned to the control level 24 h
      later. Adrenalectomy and metyrapone but not propranolol reversed the inhibition
      by ONO-4007 pretreatment of LPS-induced plasma leakage. CONCLUSIONS: A single
      injection of ONO-4007 in mice induced transient tolerance to plasma leakage
      elicited by LPS, ONO-4007 and inflammatory mediators. Endogenous corticosterone,
      at least in part, plays a role in the development of tolerance.

PMID- 11845998
TI  - Liver-infiltrating T lymphocytes cause hepatocyte damage by releasing humoral
      factors via LFA-1/ICAM-1 interaction in immunological liver injury.
AB  - OBJECTIVE AND DESIGN: To explore the mechanisms by which liver-infiltrating T
      lymphocytes cause hepatocyte damage in the liver injury induced by delayed-type
      hypersensitivity to picryl chloride. MATERIALS AND METHODS: Nonparenchymal cells
      (NPC) were isolated 12 h after liver injury elicitation and fractionated into
      Kupffer cell-enriched (Fr. A) and lymphocyte-enriched populations (Fr. B). They
      were used as the effectors for coculture with hepatocytes. RESULTS: The cells in
      total NPC and Fr. B harvested at 12 h of liver injury were increased two- and six
      fold respectively compared with those at 0 h. Fr. B, mainly including CD4+ and
      CD8+ T cells, exhibited a significantly stronger hepatotoxicity than total NPC
      did, while Fr.A did not. NPC at 12 h showed remarkably increased matrix
      metalloproteinase-2 and -9 activities indicative of infiltration potential
      through extracellular matrix. When NPC and hepatocytes were cultured in separated
      compartments in Transwell chamber, no hepatotoxicity was observed. However, 30
      min-pre-contact with hepatocytes as stimulator significantly triggered NPC
      hepatotoxicity. The acquisition of such hepatotoxic potential was significantly
      abolished by anti-LFA-1 pretreatment for NPC or anti-ICAM-1 treatment for
      hepatocytes before contact. Both aprotonin and superoxide dismutase dose
      dependently inhibited the hepatotoxicity. CONCLUSIONS: Liver-infiltrating T
      lymphocytes may be triggered by hepatocytes via LFA-1/ICAM-1 interaction to
      release toxic substances, such as proteases and oxygen radicals, which
      consequently lead to the hepatocyte damage.

PMID- 11845999
TI  - Pathologic mitoses and pathology of mitosis in tumorigenesis.

PMID- 11846000
TI  - Clonal evolution and progression of 20-methylcholanthrene-induced squamous cell
      carcinoma of mouse epidermis as revealed by DNA instability and other malignancy
      markers.
AB  - We examined the clonal evolution of skin malignant lesions by repeated topical
      applications of 20-methylcholanthrene (20-MC) to the skin, which induces
      hyperplastic epidermis, papillomatous lesion and invasive carcinoma in mice. The
      lesions were examined histologically and immunohistochemically with anti-single
      stranded DNA after acid hydrolysis (DNA-instability test), p53, VEGF, DFF45, PCNA
      and AgNORs parameters analyses. Multiple clones with increased DNA instability
      comparable to that of invasive carcinoma were noted in early-stage (2-6 weeks)
      hyperplastic epidermis, and their number increased in middle (7-11 weeks), and
      late-stages (12-25 weeks) of hyperplastic epidermis, indicating that they belong
      to the malignancy category. All papillomatous lesions and invasive carcinomas
      showed a positive DNA-instability test. Positive immunostaining for various
      biomarkers and AgNORs parameters appeared in clones with a positive DNA
      instability test in early-or middle-stage hyperplastic epidermis, and markedly
      increased in late-stage hyperplastic epidermis, papillomatous lesions and
      invasive carcinomas. The percentage of PCNA-positive vascular endothelial cells
      was significantly higher in VEGF-positive lesions with a positive DNA-instability
      test and became higher toward the late-stage of progression. Cut-woundings were
      made to papillomatous and invasive carcinoma lesions, and the regeneration
      activity of vascular endothelial cells was determined by using flash labeling
      with tritiated thymidine (3H-TdR). In small papillomatous lesions, vascular
      endothelial cells showed regenerative response, but the response was weak in
      large lesions. No such response was noted in invasive carcinomas; rather, cut
      wounding induced collapse of blood vessels, which in turn induced massive
      coagulative necrosis of cancer cells. These responses can be interpreted to
      reflect exhausted vascular growth activity due to excessive stimulation by VEGF
      overexpression, which was persistently seen from hyperplastic epidermis to
      invasive carcinoma.

PMID- 11846001
TI  - Immunohistochemical detection of early-stage carcinogenesis of oral leukoplakia
      by increased DNA-instability and various malignancy markers.
AB  - The degree of DNA instability as determined by immunohistochemical staining with
      anti-single-stranded DNA antibody after acid hydrolysis (the DNA instability
      test) was used as a marker of malignancy. The test was applied to tissues of oral
      leukoplakia assessed histopathologically as hyperplasia (38 cases), mild (12
      cases), moderate (11 cases) and severe (8 cases) dysplasia, and invasive squamous
      cell carcinoma (SCC, 20 cases). Tissues were subjected to immunohistochemical
      staining for proliferating cell nuclear antigen (PCNA), p53, DNA-fragmentation
      factor 45 (DFF45), analysis of various AgNORs parameters, and triple
      immunostaining for vascular endothelial growth factor (VEGF), CD34, and PCNA. The
      DNA instability test was positive in 20 (100%) SCC cases, 8 (100%) severe
      dysplasia cases, 8 (72.7%) moderate dysplasia cases, 6 (50.0%) mild dysplasia
      cases, and 9 (23.7%) hyperplasia cases, indicating malignancy. The proportion of
      lesions positive for PCNA, p53, DFF45, and values of AgNORs parameters steadily
      increased from hyperplasia to mild, moderate and severe dysplasia, and SCC,
      especially in those showing positive DNA instability test, indicative of
      malignancy. Based on these results, 44.9% of leukoplakia were malignant tissues,
      namely carcinoma in situ. The proportion of PCNA-positive vascular endothelial
      cells in the vicinity of VEGF-positive epithelial lesion was significantly higher
      than that of negative DNA instability lesions, as revealed by immunohistochemical
      triple staining for VEGF, CD34, and PCNA. Our results suggest that increased DNA
      instability, enhanced proliferative activity, p53 mutation, and induction of
      DFF45 and VEGF may allow cancer cell proliferation, enhance their survival by
      escaping apoptosis, and provide abundant nutrients during early-stage
      carcinogenesis of oral leukoplakia.

PMID- 11846003
TI  - Effect of interleukin 1beta on rat thymus microenvironment.
AB  - The effect of interleukin 1beta on the thymus of control and chemically
      sympathectomized adult and aged rats was studied with the aim of assessing the
      importance of adrenergic nerve fibres (ANF) in the regulation of some
      immunological functions. The whole thymus was removed from normal,
      sympathectomized (with the neurotoxin 6-OH-dopamine) and treated (interleukin
      1beta) rats. Thymic slices were stained with eosin orange (for the recognition of
      microanatomical details of the thymic microenvironment) and with Bodian's method
      for staining of nerve fibres. Histofluorescence microscopy was employed for
      staining ANF and immunofluorescence was used for detecting NPY-like
      immunoreactivity. All images were submitted to quantitative morphometrical
      analysis and statistical analysis of data. Moreover, the amount of proteins and
      noradrenaline was measured on thymic homogenates. The results indicate that in
      normal conditions the formation of the thymic nerve plexi in the rat is complex:
      the majority of ANF are destroyed after chemical sympathectomy with 6-OH-dopamine
      and do not change after treatment with interleukin 1beta; on the contrary,
      treatment with interleukin 1beta induces substantial changes in the fresh weight
      of the thymus, the thymic microenvironment, thymic nerve fibers, ANF, NPY-like
      positive nerve fibres, and on the total amount of proteins and noradrenaline in
      rat thymic tissue homogenates. Immunostimulation with interleukin 1beta induces
      substantial changes in the whole thymus, in its microenvironment and in ANF and
      NPY-like nerve fibres. After chemical sympathectomy, no significant immune
      response was evoked by interleukin 1beta, since the majority of ANF was destroyed
      by chemical sympathectomy.

PMID- 11846002
TI  - Localization of the small monomeric GTPases Rab3D and Rab3A in the AtT-20 rat
      pituitary cell line.
AB  - We investigated the cellular localization of the small GTPases Rab3D and Rab3A in
      AtT-20 cells treated with the drug Brefeldin A. Brefeldin A induces the
      redistribution of the Golgi complex into the endoplasmic reticulum and tubulation
      of endosomes. However, in Brefeldin A-treated wild-type AtT-20 cells, both Rab3D
      and Rab3A retained their distribution, indicating that they belong to a
      nonendosomal, post-Golgi compartment. Immunoelectron microscopy experiments
      indicated that both Rab3D and Rab3A localized to the ACTH-containing, large dense
      core granules. In contrast, in cell clones overexpressing a mutated form of Rab3D
      (Rab3D N135I), Rab3A did not localize to the dense core granules. Moreover, since
      our previous results showed that overexpression of Rab3D N135I severely impaired
      regulated ACTH secretion in AtT-20 cells, we sought to determine whether the
      impairment could depend on a redistribution of two key components of the
      regulated exocytosis machinery, synaptotagmin and SNAP-25. As far as
      synaptotagmin was concerned, in cell clones overexpressing Rab3D N135I, the
      protein did not localize close to the plasma membrane, in agreement with the
      previously reported defective docking of dense core granules to the plasma
      membrane. Immunofluorescence experiments showed that SNAP-25 did not change its
      localization in these cell clones. All in all, our findings strengthen the notion
      that both Rab3D and Rab3A are associated with the dense core granule compartment
      of AtT-20 cells, and that the impairment in the ACTH secretion caused by
      overexpression of a mutated Rab3D form is likely to be due to a lacking of
      granule docking to the plasma membrane, possibly because Rab3A fails to associate
      with the granules.

PMID- 11846004
TI  - Schwann cell-derived factors support serotoninergic neuron survival and promote
      neurite outgrowth.
AB  - During embryogenesis and the postnatal period, neurons and glia interact in the
      development and differentiation of specific populations of nerve cells. Both in
      the peripheral (PNS) and in the central nervous system (CNS), glial cells have
      been shown in various experimental conditions to constitute a favorable substrate
      for neural adhesion, neural polarity, shape and axonal extension, while numerous
      soluble molecules secreted by neurons influence the survival and differentiation
      of the glial cells themselves. The aim of the present work was to investigate the
      influence of postnatal Schwann cells (SC) on embryonic serotoninergic (5-HT)
      neurons of the raphe, in order to study the possible influence of the peripheral
      glia on the CNS neurons. Cultures of SC from sciatic nerve of postnatal rats and
      neurons from rat embryonic rhombencephalon were successfully established and
      cells were immunocytochemically characterized. The number of 5-HT neurons, and
      the number and length of their branches were quantified in the cultures of 5-HT
      neurons, in cultures added with Nerve Growth Factor (NGF) and Insulin-like Growth
      Factor I (IGF-I), in co-cultures with SC and in cultures added with conditioned
      medium obtained from SC cultures. The results indicated that SC have the capacity
      to promote the survival and growth of 5-HT neurons in culture, and that this
      activity is mediated by soluble factors. Although the precise nature and
      mechanism of action of the growth factor or factors produced by SC in the
      presence of 5-HT neurons was not identified, our results add more data on the
      possible activity of the peripheral glia in promoting and enhancing the survival
      and outgrowth of the CNS neurons.

PMID- 11846005
TI  - Immunohistochemical localization of NPY, VIP and 5-HT in the thyroid gland of the
      lizard, Podarcis sicula.
AB  - The thyroid gland of the lizard Podarcis sicula was immunohistochemically studied
      in adult male specimens using specific antibodies against NPY, VIP and 5-HT and
      the avidin-biotin peroxidase complex (ABC) procedure to localize the three
      peptides. Fine beaded VIP-immunoreactive nerve fibers ran between the follicles,
      and VIP-immunoreactivity was evenly distributed in the apical cytoplasm of
      follicular cells. NPY-immunoreactive fibers were found around the follicles, and,
      in the cells, immunoreactivity was localizated only in the cellular apices.
      Immunoreactivity to 5-HT was observed in the colloid, with a concentration in the
      follicular lumen exceeding that in the follicular cells. In fact, most follicles
      showed immunoreactivity in the cytoplasmic bridges formed between the apical
      portion of the follicular cells and the colloid.

PMID- 11846006
TI  - Effect of wortmannin and phorbol ester on Paramecium fluid-phase uptake in the
      presence of transferrin.
AB  - The kinetics of the uptake of the fluid phase marker Lucifer Yellow (LY), and its
      alteration by wortmannin, an inhibitor of phosphatidylinositol-3 kinase (PI-3K),
      and the PKC modulators: GF 109203 X, an inhibitor, and phorbol ester, an
      activator was studied in eukaryotic model Paramecium aurelia. Spectrophotometric
      quantification of LY accumulation was performed in the presence or absence of
      transferrin, a marker of receptor-mediated endocytosis. Internalization of LY
      showed a curvilinear kinetics: the high initial rate of LY uptake (575 ng LY/mg
      protein/hr) decreased almost 5-fold within 15 min, reaching plateau at 126 ng/mg
      protein/hr. Transferrin induced a small increase (7.5%) in the fluid phase uptake
      rate (after 5 min) followed by a small decrease at longer incubation times.
      Lucifer Yellow and transferrin (visualized by streptavidin-FITC) were localized
      in Paramecium by 3-D reconstruction by confocal microscopy. LY showed a
      scattered, diffuse fluorescence typical of fluid phase uptake whereas transferrin
      accumulated in membrane-surrounded endosomes. Wortmannin did not affect LY
      accumulation but decreased it when transferrin was present in the incubation
      medium. This suggests an effect on the transferrin uptake pathway, presumably on
      the stage of internalization in "mixing" endosomes to which transferrin and LY
      were targeted. Phorbol ester diminished LY accumulation by 22% and this effect
      persisted up to 25 min of incubation. PKC inhibitor did not affect LY uptake.
      However, in the presence of transferrin, the LY uptake increased within the first
      15 minutes followed by a rapid 20% decrease in comparison to the control. Such an
      effect of PKC modulators suggests that PMA action on fluid phase uptake is not
      directly mediated by PKC.

PMID- 11846007
TI  - Two-color fluorescence detection of Poly (ADP-Ribose) Polymerase-1 (PARP-1)
      cleavage and DNA strand breaks in etoposide-induced apoptotic cells.
AB  - During apoptosis, the nuclear enzyme Poly(ADP-Ribose) Polymerase-1 (PARP-1)
      catalyzes the rapid and transient synthesis of poly(ADP-ribose) from NAD+ and
      becomes inactive when cleaved by caspases. The regulation of these two opposite
      roles of PARP-1 is still unknown. We have recently investigated PARP-1
      activation/degradation in Hep-2 cells driven to apoptosis by actinomycin D. In
      the present work, we have extended our analysis to the effect of the DNA damaging
      agent etoposide, and paid attention to the relationship between PARP-1 cleavage
      and DNA fragmentation. An original fluorescent procedure was developed to
      simultaneously identify in situ the p89 proteolytic fragment of PARP-1 (by
      immunolabeling) and DNA degradation (by the TUNEL assay). The presence of p89 was
      observed both in cells with advanced signs of apoptosis (where the PARP-1
      fragment is extruded from the nucleus into the cytoplasm) and in TUNEL-negative
      cells, with only incipient signs of chromatin condensation; this evidence
      indicates that PARP-1 degradation in etoposide-treated apoptotic cells may
      precede DNA cleavage.

PMID- 11846008
TI  - Selenium and glutathione levels, and glutathione peroxidase activities in blood
      components of uremic patients on hemodialysis supplemented with selenium and
      treated with erythropoietin.
AB  - Patients with chronic renal failure (CRF) often have reduced concentrations of
      selenium (Se) and lowered activities of glutathione peroxidase (GSH-Px) in blood
      components. The kidney is a major source of plasma GSH-Px. We measured Se and
      glutathione levels in blood components and red cell and plasma GSH-Px activities
      in 58 uremic patients on regular (3 times a week) hemodialysis (HD). The dialyzed
      patients were divided in 4 subgroups and were supplemented for 3 months with: 1)
      placebo (bakers yeast), 2) erythropoietin (EPO; 3 times a week with 2,000 U after
      each HD session), 3) Se-rich yeast (300 microg 3 times a week after each HD), and
      4) Se-rich yeast plus EPO in doses as above. The results were compared with those
      for 25 healthy subjects. The Se concentrations and GSH-Px activities in the blood
      components of dialyzed uremic patients were significantly lower compared with the
      control group. Treatment of the HD patients with placebo and EPO only did not
      change the parameters studied. The treatment with Se as well as with Se and EPO
      caused an increase in Se levels and red cell GSH-Px activity. Plasma GSH-Px
      activity, however, increased only slowly or did not change after treatment with
      Se and with Se plus EPO. In the group treated with Se plus EPO the element
      concentration in blood components was higher compared with the group supplemented
      with Se alone. The weak or absence of response in plasma GSH-Px activity to Se
      supply indicates that the impaired kidney of uremic HD patients has reduced
      possibilities to synthesize this enzyme.

PMID- 11846009
TI  - Elements in autopsy liver tissue samples from Greenlandic Inuit and Danes. III.
      Zinc measured by X-ray fluorescence spectrometry.
AB  - The aim of the study was to measure the content of zinc (Zn) in liver tissue
      samples from Greenlandic Inuit using X-ray fluorescence spectrometry, and compare
      the results with those obtained in liver samples from Danes. Normal liver tissue
      samples was obtained at autopsy from 50 Greenlandic Inuit (27 men) with a median
      age of 61 years (range 23-83) and from 74 Danes (44 men) with a median age of 60
      years (range 15-87). In the entire series, liver zinc content in Inuit was not
      significantly different compared with Danes. There was no significant gender
      difference in liver zinc content either in Inuit or in Danes. The content of zinc
      given as median (5-95 percentile) was in Inuit 3.809 mmol/kg dry liver (2.355
      7.406), and in Danes 3.992 mmol/kg dry liver (2.499-8.645). There was a
      significant, positive correlation between liver zinc content and age in Danish
      women (r(s) = 0.43, p = 0.02), which could not be demonstrated in Danish men or
      in Inuit. Median hepatic zinc index (zinc content in mmol/kg dry weight divided
      by age in years) in Inuit was 0.073, and in Danes 0.080 (p = 0.3) without any
      significant difference between the two genders. In Inuit and Danes there was an
      inverse correlation between hepatic zinc index and age both in the two genders
      and in the entire series: Inuit: r(s) = -0.62, p < 0.0001; Danes: r(s) = -0.70, p
      < 0.0001. The results indicate that Inuit have liver zinc levels, which are
      similar to those found in Danes.

PMID- 11846010
TI  - The effect of recombinant human erythropoietin on serum selenium levels in
      hemodialysis patients.
AB  - Succesful results in the treatment of anemia, one of the main complications of
      chronic renal failure, can be achieved by the use of recombinant human
      erythropoietin (RhEPO), which is available almost fifteen years in clinics. On
      the other hand, as both chronic renal failure and maintenance hemodialysis reduce
      the levels of trace elements, this study was designed to evaluate the interaction
      potential of RhEPO with serum concentrations of selenium (Se) during four months.
      Thirty one adult hemodialysis outpatients participated in the study. Ten of them,
      not on any drug therapy to interact with RhEPO, recruited as "Control Group", and
      the remainder, on RhEPO therapy, as "RhEPO Group". Blood was drawn from the
      Control Group at the beginning of the study, and from the RhEPO Group at every
      month for four months. Serum erythropoietin leveLs were measured by a
      radioimmunoassay method and Se status by a spectrofluorometric method. It was
      found that Se levels were not affected by RhEPO treatment during 3 months of
      therapy, while an increase was seen on the fourth month. The observation
      indicates that the increase in serum Se levels would be significant in longer
      than three-month RhEPO treatment.

PMID- 11846011
TI  - Dietary phytate and mineral bioavailability.
AB  - The relation between the dietary phytate (InsP6), mineral status and InsP6 levels
      in the organism, using three controlled diets (AIN-76A, AIN-76A + 1% phytate, AIN
      76A + 6% carob seed germ), are studied. AIN-76A is a purified diet in which InsP6
      is practically absent. No important or significant differences in the mineral
      status (Zn, Cu, Fe) of blood, kidneys, liver, brain and bone, were observed,
      except iron in the brain. Thus, the amounts of iron found in the brain of rats
      fed AIN-76A + 1% InsP6 were significantly inferior to those found in rats fed AIN
      76A diet. The amounts of InsP6 found in organs of rats fed AIN-76A diet became
      very low or even undetectable while the ones found in rats fed diets that
      contained 1% and 0.12% (AIN-76A + 6% carob seed germ) InsP6, were considerably
      higher and similar. Moreover the majority of rats fed AIN-76A diet exhibited
      calcifications at the corticomedullary junctions, whereas no calcifications were
      detected in rats fed the other two diets. From these results, it can be deduced
      that there was no important adverse effects on mineral status as a consequence of
      the presence of InsP6 in the studied diets. Besides, considering that a 0.12%
      InsP6 contained in the AIN-76A purified diet through the addition of a 6% of
      carob seed germ to this diet, produced the same beneficial effects as the direct
      addition of a 1% of InsP6 and no negative effects on mineral status was observed,
      it can be concluded that the value of the presence of InsP6 at adequate amounts
      in the diet is remarkable and must be favourably considered.

PMID- 11846012
TI  - Induction of metallothionein by exposure to normobaric 100% oxygen atmosphere in
      rats with different zinc supply.
AB  - The objective of this study was to determine the effects of an oxygen enriched
      environment on the induction of the metalloprotein metallothionein (MT) and its
      relation to zinc metabolism in rats supplied with different levels of dietary
      zinc. Male albino rats were fed purified diets based on maize starch, egg white,
      saccharose and soybean oil differing in the concentration of zinc (1; 20; 100;
      500 mg Zn/kg diet). At a dietary zinc supply of 1 mg/kg, the rats developed a
      zinc deficiency indicated by visual and biochemical parameters. At the end of the
      37-day feeding period, half of the rats were exposed to 100% oxygen for 12 h. The
      oxygen treatment significantly reduced plasma zinc in the zinc supplemented rats
      and reduced it in tendency in the zinc deficient rats. The MT concentration was
      increased in the zinc supplemented groups in the liver, kidney and lung. The
      oxygen treatment elevated the metallothionein concentration in the two high zinc
      supplemented groups (100 and 500 mg Zn/kg diet) in the liver. The response of the
      zinc concentration in plasma and of hepatic metallothionein levels to oxygen
      exposure indicates a role of metallothionein in zinc distribution or interactions
      with other trace elements to support antioxidant capacity, rather than an impact
      on direct scavenging activity of free radicals.

PMID- 11846013
TI  - Inhibition of zinc absorption by iron depends on their ratio.
AB  - Previous studies upon zinc-iron interactions gave conflicting results that could
      come from differences in protocol design or in trace element status of subjects.
      The present work assessed the influence of zinc : iron ratio and iron deficiency
      upon zinc absorption. The digestive absorption of zinc sulphate (100 micromol
      Zn/l) in presence of iron gluconate was studied in perfused jejunal loops (n =
      6/group) of normal rats (range 0-1000 micromol Fe/l) and iron deficient rats (200
      750 micromol Fe/l). In normal rats no significant iron inhibition on zinc
      absorption occurred at Fe:Zn ratio below 2:1. At higher ratios zinc uptake and
      net absorption decreased significantly (p<0.05). Between 2:1 and 5:1 a dose
      dependent inhibition of zinc absorption occurred and reached a plateau beyond
      this ratio. In iron deficient animals no changes in zinc uptake, mucosal
      retention and absorption compared to normal animals occurred at ratio 2:1. At
      higher ratios differences were observed at every zinc absorption step except for
      mucosal retention at 7.5:1 ratio. Iron-zinc interactions depend on their ratio
      and on previous trace elements status of subjects. Due to the wide and unknown
      variations that were likely to occur between the subjects of previous human and
      experimental studies, these results could explain some of the discrepancies
      between their results.

PMID- 11846014
TI  - Transport of silver in virgin and lactating rats and relation to copper.
AB  - Virgin and lactating Sprague Dawley rats were used to determine whether the
      pathways of silver transport to tissues and milk resemble those for copper. Rats
      were injected i.p.with small amounts of 110AgNO3. Blood and tissues were examined
      at various times thereafter for total radioactivity and for incorporation into
      copper binding proteins in plasma and milk. As with 67Cu, much of the 110Ag was
      rapidly incorporated into the liver. Skeletal muscle, spleen, mammary gland,
      ovaries, uterus and adrenals also were significant initial accumulation sites,
      with or without lactation. Lactation enhanced uptake by the mammary gland, and
      radioactivity rapidly entered the milk and milk ceruloplasmin. In the plasma,
      most of the 110Ag bound to a single component of apparent molecular weight 800 k
      throughout the 52 h period examined. A small proportion was also incorporated
      into plasma ceruloplasmin, as determined by immunoprecipitation and native gel
      electrophoresis. There was little or no association of 110Ag with albumin or
      transcuprein. The binding of 110Ag to the 800 kDa protein was tight. Off rates
      during pH 7 dialysis were <2.5%/day even in the presence of 100 microM histidine
      or Cu(II), but were accelarated by mercaptoethanol. Subunits of 145 and 45 kDa in
      virtually pure peak fractions were those of alpha1-macroglobulin. We conclude
      that silver resembles copper in aspects of its tissue distribution, response to
      lactation, and incorporation into ceruloplasmin. However its main plasma carrier
      appears to be alpha1-macroglobulin, a different macroglobulin than that involved
      in copper transport.

PMID- 11846015
TI  - Bioavailability study of dried microencapsulated ferrous sulfate--SFE 171--by
      means of the prophylactic-preventive method.
AB  - Microencapsulated ferrous sulfate with soy lecithin (SFE-171) has been used as an
      iron source for the fortification of milk and dairy products. With the purpose to
      extend the use of this agent to other kind of foods or even to pharmaceutical
      preparations for oral administration, the SFE-171 was turned into a fluid powder
      (SFE-171-P) by means of vacuum drying. The iron bioavailability (BioFe) of SFE
      171-P was evaluated in this work by means of the prophylactic-preventive method
      in rats, using ferrous sulfate as reference standard. Both iron sources were
      separately added to a basal diet of low iron content in a concentration of 10 mg
      iron/kg diet. Two groups of 10 weaned rats 25 days old received the fortified
      diets during 28 days, while a third group of the same size received the basal
      diet without iron additions. The weights and haemoglobin concentrations (HbC) of
      every animal were determined before and after the treatment, thus allowing the
      calculation of the mass of iron incorporated into haemoglobin (HbFe) during this
      period. The BioFe of the iron sources were obtained as the percentage ratio
      between the HbFe and the mass of iron consumed by each animal. The results were
      also given as Relative Biological Value (RBV), which relates the BioFe of the
      studied source with that of the reference standard. The liver iron concentration
      (LIC) of each animal was determined at the end of the experiment in order to
      evaLuate the influence of the studied iron sources on the liver iron stores. SFE
      171-P presented BioFe, RBV and LIC values of (47 +/- 7)%, 109% and (46.6 +/- 3.4)
      mg/kg respectively, while the corresponding values for the reference standard
      were of (43 +/- 7)%, 100% and (45.0 +/- 4.7) mg/kg. These results show that the
      drying process used to produce the SFE-171-P does not affect its bioavailability,
      which is also adequate for the potential use of this product in food
      fortification or with pharmaceutical purposes.

PMID- 11846016
TI  - Serological status for Chlamydophila psittaci, Newcastle disease virus, avian
      polyoma virus, and Pacheco disease virus in scarlet macaws (Ara macao) kept in
      captivity in Costa Rica.
AB  - From 1998 to 1999, a total of 128 blood samples were collected from scarlet
      macaws (Ara macao), kept in captivity in 11 different aviaries located in six
      provinces of Costa Rica. The sera were examined for antibodies directed against
      Chlamydophila psittaci, Newcastle disease virus (NDV), avian polyoma virus (APV),
      and Pacheco disease virus (PDV). Testing by enzyme-linked immunosorbent assay
      (ELISA), showed 16 (12.39%) of the samples (n = 129) exhibited antibodies
      directed against C. psittaci. Employing haemagglutination inhibition tests for
      NDV antibodies, all of the samples were found to be negative. The prevalence of
      antibodies specific for APV was tested with a blocking ELISA and serum
      neutralization tests (SNT) and 12 of 128 samples (9.37%) were found to be
      positive with both tests. In SNT, two out of 128 samples (1.56%) were positive
      for PDV. This is the first description of the serological status in scarlet
      macaws in captivity in Costa Rica. The study demonstrates the absence of NDV
      antibodies in the birds investigated on one hand, but also indicates a health
      hazard for numerous avian species due to the risk of infections with C. psittaci,
      APV or PDV.

PMID- 11846017
TI  - An attenuated herpes vaccine may protect Gyr hybrids from fatal inclusion body
      hepatitis. A preliminary report.
AB  - Four Gyr hybrids were used for this falcon herpes vaccine experiment. Three
      falcons were given 1 ml of an attenuated falcon herpesvirus vaccine (DuFaHe)
      subcutaneously twice within 14 days, whereas the fourth falcon was used as a
      control. Eighteen days after the booster vaccination, all four Gyr hybrids were
      intranasally and ocularly challenged with a virulent low-passage falcon
      herpesvirus. The control falcon died 9 days after challenge with typical lesions
      of herpesvirus inclusion body hepatitis. The three vaccinated falcons
      seroconverted and did not show any symptoms. Following the challenge their
      antibody titres to falcon herpesvirus increased. No herpesvirus was isolated from
      any of the cloacal swabs taken during this experiment, indicating that there was
      no danger for any other birds from DuFaHe. This experiment shows that falcons can
      be protected from herpesvirus infection by an attenuated herpesvirus vaccine.
      However, it should be stressed that only four falcons were used for this
      experiment.

PMID- 11846018
TI  - A comparative study of the preventive use of tilmicosin phosphate (Pulmotil
      premix) and Mycoplasma hyopneumoniae vaccination in a pig herd with chronic
      respiratory disease.
AB  - This study was conducted to compare the effects of a preventive in-feed
      medication programme using tilmicosin (Pulmotil 200 premix, Elanco Animal Health)
      at 200 p.p.m. with those of Mycoplasma hyopneumoniae (Mh) vaccination programme
      (Stellamune Mycoplasma, Pfizer Animal Health). A pig herd with chronic
      respiratory disease in which infection with Mh played an important role was
      selected, and a total of 204 piglets were randomly allocated to either the
      medication (P) or the vaccination (V) group. Pigs in the P group received
      medicated feed for 3 weeks after weaning (days 34-55), and for 2 weeks late in
      the nursery period (days 77-98). The piglets in the V group were vaccinated twice
      intramuscularly, at 4 and 22 days of age. The two groups were compared on the
      basis of average daily gain (ADG), feed conversion rate (FCR), additional
      curative medication days (CMD), overall mortality (major variables), a coughing
      index, pneumonia lesions, and serology against Mh, influenza H1N1 and influenza
      H3N2 viruses, Actinobacillus pleuropneumoniae (App) and porcine reproductive and
      respirator, syndrome virus (PRRSV) (minor variables). No significant differences
      (P > 0.05) were observed for ADG (555 g/day in P group; 567 g/day in V group),
      FCR (2.64 in P group; 2.41 in V group) and mortality rate (11% in P group; 7% in
      V group). The average number of additional curative medication days (CMD) per pig
      was significantly higher (P < 0.01) in the P group (1.5) than in the V group
      (0.58). At slaughter age, the serological results and the prevalence of
      macroscopic lung lesions were comparable in the two groups (P > 0.05). With the
      exception of CMD, the preventive use of tilmicosin at this swine farm was found
      to confer similar beneficial effects to Mh vaccination.

PMID- 11846019
TI  - The value of the determination of anti-Aspergillus IgG in the serodiagnosis of
      canine aspergillosis: comparison with galactomannan detection.
AB  - Diagnosis of canine aspergillosis is difficult using currently available methods.
      It often passes unnoticed or is diagnosed in the later phases of the disease. We
      developed an ELISA technique to detect anti-Aspergillus antibodies in canine
      serum using an Aspergillus antigenic mycelial extract, which could then be used
      for the diagnosis of canine aspergillosis. We used a cut-off of X + 3SD obtained
      from 20 control sera. The test was performed on 46 dogs with lesions indicating
      possible aspergillosis and gave nine positive results: one systemic mycosis, two
      discospondylitis, one uveitis, two bronchopulmonary processes and three rhinitis.
      We compared this methodology with the PLATELIA technique in the follow-up of the
      affected dogs, obtaining the same limitations as in the diagnosis of human
      aspergillosis. We consider our ELISA technique using sera samples a speedy, safe
      and reliable method which enables us to follow up the evolution of the disease
      and the efficacy of the therapy chosen. A definitive diagnosis must still take
      into account the results of other tests such as clinical examination,
      radiographic studies, endoscopy and biopsy.

PMID- 11846020
TI  - Rapid immunohistochemical detection of Rhodococcus equi in impression smears from
      affected foals on postmortem examination.
AB  - The first objective of this study was to develop an immunohistochemical procedure
      for rapid detection of Rhodococcus equi in impression smears from affected organs
      of foals on postmortem examination. The second aim was to demonstrate whether R.
      equi can be detected in smears of tracheal exudates collected from the same foals
      using an immunohistochemical method. Impression smears and cryostat and paraffin
      embedded sections were made from the lungs and mediastinal lymph nodes of three
      foals (A, B and C) that had died of respiratory disease caused by R. equi, and
      also from the caudal mesenteric lymph node of foal A. Impression smears were made
      from the tracheal exudates of all foals. An affinity purified rabbit IgG was used
      for the immunohistochemical demonstration of R. equi. This antibody reacted with
      serotype 1 of R. equi in Ouchterlony's immunodiffusion and in the passive
      haemagglutination test, but not with other serotypes or with Streptococcus equi
      ssp. equi or Staphylococcus aureus, and failed to give an immunohistochemical
      reaction with Mycobacterium bovis or M. paratuberculosis. The immunohistochemical
      method proved to be of identical sensitivity to bacterial culture; moreover, from
      the lungs and mediastinal lymph nodes of one foal, R. equi could only be detected
      by this method. R. equi was demonstrated in smears of the tracheal exudates of
      all three foals. The results of this study indicate that the immunohistochemical
      method may be used for the rapid detection of R. equi in impression smears from
      the affected organs, especially abscesses, obtained postmortem, and possibly as a
      tool for diagnosing R. equi pneumonia in live foals by examining smears of
      tracheal aspirates.

PMID- 11846021
TI  - Role of collagen in adherence of Streptococcus uberis to bovine mammary
      epithelial cells.
AB  - We reported previously that pre-incubation of Streptococcus uberis with collagen
      induced expression of S. uberis surface proteins. In a subsequent study, we
      showed that incubation of S. uberis with extracellular matrix proteins,
      particularly collagen, increased adherence and internalization of S. uberis to
      mammary epithelial cells. In the present report, the potential mechanism by which
      S. uberis exploits the presence of collagen to enhance adherence to bovine
      mammary epithelial cells was evaluated. Adherence assays were conducted with S.
      uberis pre-treated with and without collagen and co-cultured in medium
      supplemented with or without collagen. Pre-incubation with collagen followed by
      co-culture in medium containing collagen up-regulated ligands that enhanced
      adherence of S. uberis to mammary epithelial cells. Collagen-up-regulated
      ligand(s) also increased adherence of S. uberis to mammary epithelial cells in
      the absence of collagen, but adherence was lower than when collagen was present
      during the adherence assay. Chloramphenicol was added to the culture medium to
      inhibit bacterial protein synthesis. Adherence decreased significantly in
      chloramphenicol-treated S. uberis pre-treated or co-cultured in the presence of
      collagen. These results suggest that S. uberis expresses ligands with affinity
      for collagen that are up-regulated by collagen. We hypothesize that these ligands
      increase adherence by using collagen as a bridge between the bacterium and host
      cell and/or by direct interaction with host cell receptor(s).

PMID- 11846022
TI  - Clostridium perfringens toxin types in hooded seals in the Greenland Sea,
      determined by PCR and ELISA.
AB  - Very little is known about the occurrence of Clostridium perfringens and of
      diseases caused by this anaerobic bacterium in marine mammals, especially those
      that are free-living. During a scientific expedition to the Greenland Sea (West
      Ice) in spring 1999, faeces samples from 70 hooded seals (Cystophora cristata)
      were taken to isolate C. perfiringens. Subsequently, PCR analysis of the isolates
      was performed with oligonucleotide primers of the genes encoding the four major
      lethal toxins (alpha, beta, epsilon and iota) for classification of toxin type
      and of the genes encoding C. perfringens beta2-toxin and enterotoxin for further
      subclassification. In addition, a commercial ELISA kit for detection of C.
      perfringens alpha, beta- and epsilon-toxin was used. C. perfingens was isolated
      in samples from 38 (54.3%) hooded seals. All isolates were C. perfringens toxin
      type A (alpha-toxin positive). This is the first report on the occurrence of C.
      perfringens in this arctic marine mammal species. Myositis and enterotoxemia
      caused by C. perfrigens were described in other marine mammals and it may be
      assumed that the pathogenesis of an outbreak of disease is similar to that
      encountered in terrestrial animals. Although there is some controversy
      surrounding the enteropathogenicity and virulence of alpha-toxin (concerning
      enterotoxemia), this study suggests that a possible outbreak of enterotoxemia
      caused by C. perfringens type A in hooded seals may, however, not be excluded.

PMID- 11846023
TI  - Development of a PCR-based method for specific identification of genotypic
      markers of shiga toxin-producing Escherichia coli strains.
AB  - A simple, rapid and specific PCR-based method for identification of shiga toxin
      producing Escherichia coli (STEC) was developed. The procedure involves
      amplification of the E. coli-specific universal stress protein A (uspA) gene
      (uspa-PCR), with the primer pair described by other authors, which allows
      differentiation of E. coli (STEC and non-STEC) from other gram-negative bacteria
      followed by identification of the main genetic virulence traits of the uspA
      positive isolates. For this purpose, two multiplex PCR assays, based on
      previously published primer sequences, were established. Assay 1 (mPCR-1) uses
      three primer pairs and detects the genes encoding O157 (rfb), enterohemolysin
      (ebly) and shiga toxin (stx), generating amplification products of 420, 534 and
      230 bp, respectively. Assay 2 (mPCR-2) uses four primer pairs specific for rfb
      (E. coli O157), eaeA (intimin), stx1 and stx2 (shiga toxin 1 and 2,
      respectively), generating PCR amplicons of 420, 840, 348 and 584 bp,
      respectively. These two assays were validated by testing several E. coli
      reference strains and 202 previously characterized E. coli isolates originating
      from calves and from children, and 100% agreement with previous results was
      obtained. The method developed can be used for specific identification of STEC
      bacteria including those of the O157 serogroup.

PMID- 11846024
TI  - Ribozyme activity in the genomic and antigenomic RNA strands of hepatitis delta
      virus.
AB  - In the hepatitis delta virus, ribozymes are encoded in both the genomic strand
      RNA and its complement, the antigenomic strand. The two ribozymes are similar in
      sequence and structure, are most active in the presence of divalent cation and
      catalyze RNA cleavage reactions which generate a 5'-hydroxyl group and a 2',3'
      cyclic phosphate group. Recent progress has been made in understanding the
      catalytic mechanism. One key was a crystal structure of the genomic ribozyme that
      revealed a specific cytosine positioned to act as a general acid-base catalyst.
      The folding of the ribozyme in the context of the longer viral RNA is another
      area of interest. The biology requires that each ribozyme act only once, and
      mechanisms proposed for regulation of ribozyme activity sometimes invoke
      alternative RNA structures. Likewise, interference of ribozyme function by
      polyadenylation of the antigenomic RNA strand could be controlled through
      alternative structures, and a model for such control is proposed.

PMID- 11846025
TI  - Regulation of cyclin-Cdk activity in mammalian cells.
AB  - Cell cycle progression is driven by the coordinated regulation of the activities
      of cyclin-dependent kinases (Cdks). Of the several mechanisms known to regulate
      Cdk activity in response to external signals, regulation of cyclin gene
      expression, post-translational modification of Cdks by phosphorylation
      dephosphorylation cascades, and the interaction of cyclin/Cdk complexes with
      protein inhibitors have been thoroughly studied. During recent years, much
      attention has also been given to mechanisms that regulate protein degradation by
      the ubiquitin/proteasome pathway, as well as to the regulation of subcellular
      localization of the proteins that comprise the intrinsic cell cycle clock. The
      purpose of the present review is to summarize the most important aspects of the
      various mechanisms implicated in cell cycle regulation.

PMID- 11846026
TI  - The multifaceted Paneth cell.
AB  - Paneth cells (PCs) were described over a century ago as granulated cells located
      at the base of small intestinal crypts, the 'crypts of Lieberkuhn.' Various
      histochemical staining procedures were developed that identified PCs based on
      their distinctive granule-staining pattern. Early on, PCs were proposed to
      perform a specialized function other than absorption of digested nutrients, the
      predominant task of the small intestinal epithelium. Since then, many
      constituents of the PC granules have been biochemically characterized. The
      presence of various granule-associated antimicrobial substances and their release
      upon microbial challenge suggest that PCs function as specialized defense cells
      in the small intestine. Altered resistance to microbial infection in animal
      models with disrupted or augmented PC function provides further support for the
      host defense role of PCs. Other PC components suggest that PCs may also
      participate in the regulation of lumenal ionic composition, crypt development,
      digestion, and intestinal inflammation.

PMID- 11846027
TI  - Association of the Epstein-Barr virus latent membrane protein 1 with lipid rafts
      is mediated through its N-terminal region.
AB  - The latent membrane protein 1 (LMP1) encoded by the Epstein-Barr virus acts like
      a constitutively activated receptor of the tumor necrosis factor receptor (TNFR)
      family and is enriched in lipid rafts. We showed that LMP1 is targeted to lipid
      rafts in transfected HEK 293 cells, and that the endogenous TNFR-associated
      factor 3 binds LMP1 and is recruited to lipid rafts upon LMP1 expression. An LMP1
      mutant lacking the C-terminal 55 amino acids (Cdelta55) behaves like the wild
      type (WT) LMP1 with respect to membrane localization. In contrast, a mutant with
      a deletion of the 25 N-terminal residues (Ndelta25) does not concentrate in lipid
      rafts but still binds TRAF3, demonstrating that cell localization of LMP1 was not
      crucial for TRAF3 localization. Moreover, Ndelta25 inhibited WT LMP1-mediated
      induction of the transcription factors NF-kappaB and AP-1. Morphological data
      indicate that Ndelta25 hampers WT LMP1 plasma membrane localization, thus
      blocking LMP1 function.

PMID- 11846029
TI  - Molecular basis of osteoarthritis: biomechanical aspects.
AB  - The unique biomechanical properties of healthy cartilage ensure that articular
      cartilage is able to transmit force between the joints while maintaining almost
      friction-free limb movement. In osteoarthritis, the biomechanical properties are
      compromised, but we still do not understood whether this precedes the onset of
      the disease or is a result of it. This review focuses on the physical changes to
      cartilage with age, disease, and mechanical loading, with specific reference to
      the increased collagen cross-linking that occurs with age (nonenzymatic
      glycation), and the response of chondrocytes to physiological and pathological
      loads. In addition, the biomechanical properties and matrix biosynthesis of
      cartilage from various joint surfaces of the knee and ankle are compared to
      elucidate reasons why the ankle is less affected by progressive osteoarthritis
      than the knee.

PMID- 11846028
TI  - Molecular basis for differences between human joints.
AB  - The molecular program of a cell determines responses including induction or
      inhibition of genes for function and activity, and this is true of the cells
      within articular cartilage, a major functional component of the joint. While our
      studies have previously focussed on differences in the molecular programs of the
      cells within the superficial and deep zones, we have recently begun to focus on
      relative differences between joints, such as the knee and ankle. In the human,
      these joints vary greatly in their susceptibility to joint diseases, such as
      osteoarthritis (OA). We have predicted that there would be a molecular basis for
      differences between joints that could lead to differences in susceptibility to
      OA, if inherent pathways locked into the resident cells induce differences in
      their response to their environment. We have been able to show that there are
      differences between the matrix components and water content; these properties
      correspond to a higher equilibrium modulus and dynamic stiffness but lower
      hydraulic permeability and serve to make the ankle cartilage stiffer, slowing
      movement of molecules through the cartilage. In addition to these biochemical
      differences in the cartilage matrix, we have also identified relative differences
      in the strength of the response to stimulation of chondrocytes from knee and
      ankle. The stronger response of the knee chondrocytes includes factors that
      increase damage to the cartilage matrix, such as a depression of matrix synthesis
      and increased enzyme activity. This response by the knee chondrocytes results in
      enzyme damage to the matrix that the cells may not be able to repair, while the
      weaker response of the ankle chondrocytes may allow the cells to repair their
      matrix damage.

PMID- 11846030
TI  - Introduction: molecular and biomechanical basis of osteoarthritis.
AB  - Osteoarthritis has developed into the most common chronic disease in the highly
      industrialized nations. Moreover, because of the prevalence of the disease in the
      elderly, this trend occurs worldwide as a consequence of increasing longevity due
      to the overall improvement in living conditions and health status. In contrast,
      research on osteoarthritis is still financially marginalized within biomedical
      research, so that the molecular and biophysical bases for disease initiation and
      progression are largely unmapped. The following sequence of five reviews
      highlights a remarkable change in that body of knowledge taking place at the
      beginning of the World Health Organization (WHO) 'Bone and Joint Decade 2001
      2010'. The data and ideas presented in these articles reflect to some extent the
      guidelines set up by the WHO and by the National Institutes of Health of the USA
      and therefore allow a glimpse into the directions that research in osteoarthritis
      will take in the future.

PMID- 11846031
TI  - CD44 and integrin matrix receptors participate in cartilage homeostasis.
AB  - Articular chondrocytes express the matrix receptors CD44 and integrins. Both of
      these receptors exhibit interactions with adjacent extracellular matrix
      macromolecules. In addition, both integrins and CD44 have the capacity for signal
      transduction as well as modulated interactions with the actin cytoskeleton. As
      such, both receptor families provide the chondrocytes a means to detect changes
      in matrix composition or to function as mechanotransducers. Disruption of CD44 or
      integrin-mediated cell-matrix interactions, either experimentally induced or when
      present in osteoarthritis, have profound effects on cartilage metabolism. Thus,
      CD44 and integrin receptors play a critical role in maintaining cartilage
      homeostasis.

PMID- 11846032
TI  - Molecular aspects of pathogenesis in osteoarthritis: the role of inflammation.
AB  - Arthritic diseases cause enormous burdens in terms of pain, crippling, and
      disability. Osteoarthritis (OA), the most common form of arthritis, is
      characterized by a slow progressive degeneration of articular cartilage. The
      exact etiology of OA is not known, but the degradation of cartilage matrix
      components is generally agreed to be due to an increased synthesis and activation
      of extracellular proteinases, mainly matrix metalloproteinases. Insufficient
      synthesis of new matrix macromolecules is also thought to be involved, possibly
      as a consequence of deficient stimulation by growth factors. Although OA is
      defined as a noninflammatory arthropathy, proinflammatory cytokines such as
      interleukin-1 have been implicated as important mediators in the disease. In
      response to interleukin-1, chondrocytes upregulate the production of nitric oxide
      and prostaglandin E2, two factors that have been shown to induce a number of the
      cellular changes associated with OA. The generation of these key signal molecules
      depends on inducible enzymes and can be suppressed by pharmacological inhibitors.

PMID- 11846033
TI  - Molecular pathology and pathobiology of osteoarthritic cartilage.
AB  - The biochemical properties of articular cartilage rely on the biochemical
      composition and integrity of its extracellular matrix. This matrix consists
      mainly of a collagen network and the proteoglycan-rich ground substance. In
      osteoarthritis, ongoing cartilage matrix destruction takes place, leading to a
      progressive loss in joint function. Beside the degradation of molecular matrix
      components, destabilization of supramolecular structures such as the collagen
      network and changes in the expression profile of matrix molecules also take
      place. These processes, as well as the pattern of cellular reaction, explain the
      pathology of osteoarthritic cartilage degeneration. The loss of histochemical
      proteoglycan staining reflects the damage at the molecular level, whereas the
      supramolecular matrix destruction leads to fissuring and finally to the loss of
      the cartilage. Chondrocytes react by increasing matrix synthesis, proliferating,
      and changing their cellular phenotype. Gene expression mapping in situ and gene
      expression profiling allows characterization of the osteoarthritic cellular
      phenotype, a key determinant for understanding and manipulating the
      osteoarthritic disease process.

PMID- 11846034
TI  - Family growth: the eukaryotic DNA polymerase revolution.

PMID- 11846035
TI  - The spread of tobacco mosaic virus infection: insights into the cellular
      mechanism of RNA transport.
AB  - Interactions of plant cells with pathogens or other biotic or abiotic
      environmental factors can give rise to systemic defense responses that rely upon
      the cell-to-cell and systemic transport of specific signals. A novel type of
      systemic signaling was revealed by recent evidence indicating the existence of
      RNA species that travel cell to cell and through the vasculature. The most
      compelling evidence for intercellular and systemic transport of RNA in plants is
      provided by viroids and viruses that apparently use the endogenous transport
      machinery to spread infection. The cell to cell movement of plant viruses occurs
      through small pores in the cell wall known as plasmodesmata and depends on virus
      encoded 'movement proteins'. This review summarizes current knowledge of Tobacco
      mosaic virus infection with emphasis on the mechanism by which this virus targets
      its RNA genome from sites of replication to plasmodesmata to achieve
      intercellular spread.

PMID- 11846036
TI  - The Ror receptor tyrosine kinase family.
AB  - Receptor tyrosine kinases (RTKs) participate in numerous developmental decisions.
      Ror RTKs are a family of orphan receptors that are related to muscle specific
      kinase (MuSK) and Trk neurotrophin receptors. MuSK assembles acetylcholine
      receptors at the neuromuscular junction, and Trk receptors function in the
      developing nervous system (reviewed in [3-5]). Rors have been identified in
      nematodes, insects and mammals. Recent studies have begun to shed light on Ror
      function during development. In most species, Rors are expressed in many tissue
      types during development. Analyses of mutants that are defective in the single
      nematode Ror demonstrate a role in cell migration and in orienting cell polarity.
      Mice lacking one of the two Ror gene products display defects in bone and heart
      formation. Similarly, two different human bone development disorders, dominant
      brachydactyly B and recessive Robinow syndrome, result from mutations in one of
      the human Ror genes.

PMID- 11846037
TI  - Molecular paleontology.
AB  - Molecular paleontology, i.e., the recovery of DNA from ancient human, animal, and
      plant remains is an innovative research field that has received progressively
      more attention from the scientific community since the 1980s. In the last decade,
      the field was punctuated by claims which aroused great interest but eventually
      turned out to be fakes--the most famous being the sequence of dinosaur DNA later
      shown to be of human origin. At present, the discipline is characterized by some
      certainties and many doubts. We know, for example, that we have reasonable
      chances to recover authentic DNA from a mammoth carcass, while our chances are
      negligible (or nonexistent) in the case of a dynastic mummy from Egypt. On the
      other hand, though we are developing convincing models of DNA decay in bone, we
      are not yet able to predict whether a certain paleontological or archeological
      site will yield material amenable to DNA analysis. This article reviews some of
      the most important and promising investigations using molecular paleontology
      approaches, such as studies on the conservation of DNA in human bone, the quest
      for ancient DNA in permafrost-frozen fauna, the Tyrolean iceman, and the
      Neandertals.

PMID- 11846038
TI  - Papillary glioneuronal tumor--a new tumor entity.
AB  - Glioneuronal neoplasms of the CNS comprises a heterogeneous group of generally
      low-grade tumors expressing glial and neuronal cells of varying differentiation.
      Recently, a new variant of the glioneuronal tumors has been identified. We
      present a case of a glioneuronal tumor located in the left frontal lobe of a 16
      year-old boy who developed seizures 6 months after brain concussion. MR scan
      demonstrated an irregular, but well circumscribed, mixed cystic and solid tumor
      with contrast enhancement in the solid part. Histology showed a papillary
      glioneuronal tumor. The tumor is indolent with no sign of recurrence after gross
      total resection.

PMID- 11846039
TI  - Combined therapy of cerebral arteriovenous malformations: histological
      differences between a non-adhesive liquid embolic agent and n-butyl 2
      cyanoacrylate (NBCA).
AB  - OBJECTIVE: Based on 2 casuistics, the intraoperative qualities of a new, non
      adhesive liquid embolic agent (Onyx, Micro Therapeutics. Inc., Irvine, CA, USA)
      are to be compared to those of n-butyl 2-cyanoacrylate (NBCA) with regard to the
      histopathological results after preoperative embolization of a cerebral
      arteriovenous malformation (AVM). PATIENTS AND METHODS: In a case example, the
      intraoperative quality of the nidus after embolization of a parieto-occipital AVM
      with Onyx--a new, non-adhesive liquid embolic agent--consisting of ethylene-vinyl
      alcohol copolymer (EVOH), dimethyl sulfoxide (DMSO) and tantalum, is described.
      In the second patient, embolization of a frontal high-flow AVM was performed with
      NBCA. Both patients underwent surgery with complete resection ofthe AVM. RESULTS:
      From a neurosurgical point of view, Onyx is suitable for preoperative
      embolization of AVMs, because the nidus intraoperatively remains elastic and
      formable and can be dissected from the surrounding brain tissue quite well by
      microsurgical technique. Inflammatory reactions can be found mainly in the lumina
      of the vessels. CONCLUSIONS: Onyx promises to be an embolic agent well suitable
      for subsequent neurosurgical resection. Further studies considering various
      intervals of time between embolization and resection as well as histopathological
      and electron microscopical examinations are necessary for evaluation of our first
      experience with this new embolization agent.

PMID- 11846040
TI  - Adult-onset xeroderma pigmentosum neurological disease--observations in an
      autopsy case.
AB  - Xeroderma pigmentosum (XP) is an inherited disease with defective DNA repair.
      Patients develop skin cancer because of unrepaired DNA damage produced by the
      ultraviolet radiation (UV) in sunlight. Many XP children also develop XP
      neurological disease (ND), consisting of sensorineural hearing loss (SNHL) and a
      primary neuronal degeneration of the central and peripheral nervous systems.
      Since the harmful UV in sunlight cannot reach the nervous system, the cause of
      the death of XP neurons has been hypothesized to result from the inability to
      repair their DNA that has been damaged by endogenous metabolites. Progressive XP
      ND originating in an adult has been identified in only a single case. Although
      clinically asymptomatic at the age of 47 years, the patient had audiometric
      evidence of a developing mild SNHL together with elicited signs and
      electrophysiologic evidence of a peripheral neuropathy. She died of metastatic
      endocervical adenocarcinoma at 49 years of age. We describe here the
      neuropathological findings in this patient, including examination of the inner
      ear. Despite clinical evidence of SNHL, there were no anatomic abnormalities of
      the inner ear. However, the dorsal root ganglia (DRG) showed ongoing neuronal
      loss. Our findings indicate that XP ND originating in this adult is, like XP ND
      in children, a primary neuronal degeneration that manifests first in the
      peripheral nervous system.

PMID- 11846041
TI  - Xanthogranuloma of the Erdheim-Chester type within the sellar region: case
      report.
AB  - Manifestations of Erdheim-Chester disease in the central nervous system are very
      rare. Cases with localization in the retroorbital space, hypothalamic area and
      posterior pituitary as well as intracerebral lesions are known. In our
      neurosurgical unit, a 51-year-old male patient with a history of hypophyseal
      insufficiency and visual deficits underwent surgery for a pituitary lesion.
      Histological and immunohistochemical examination revealed a xanthogranulomatous
      lesion composed of very large CD68-positive foam cells with small nuclei and some
      Touton-like giant cells, histiocytes, as well as loci with small lymphocytes and
      isolated eosinophilic granuolcytes, embedded in fibrotic tissue. Based on these
      findings, the histological diagnosis was a xanthogranuloma of the Erdheim-Chester
      type.

PMID- 11846042
TI  - Comparative morphometry of myelinated nerve fibres in the normal and
      pathologically altered human sural and tibial nerve.
AB  - To assess neuropathological changes in human nerves, biopsies are usually
      performed on the sural nerve or other nerves supplying only a small area of skin.
      It is not yet clearly understood to what extent the changes found in this sensory
      nerve correspond to the changes found in other distal sensomotory nerves. To
      answer this question, we made a comparative morphometric analysis of the sural
      and tibial nerve. In 39 autopsy cases (aged 22 - 90 years) the sural and the
      tibial nerve were subject of image analysis. The histological picture in this
      study group was clearly influenced by neuropathological changes as well as age
      related changes. For each morphometric parameter in the sural and tibial nerve,
      we evaluated Pearson's correlation. The highest coefficient of correlation (r)
      was seen in those parameters that represented the condition of the myelin sheath
      area: the density of nerve fibre area (sum of measured nerve, fibre
      areas/analyzed endoneural area) (r = 0.86) and the density of myelin sheath area
      (sum of measured myelin areas/analyzed endoneural area) (r = 0.86). Similar
      correlations were obtained for the mean of axon diameter (r = 0.82), the
      numerical density of nerve fibre count (nerve fibre count/analyzed endoneural
      area) (r = 0.77), the mean of nerve fibre diameter (r = 0.77) and the mean of
      myelin sheath thickness (r = 0.72). Our results revealed a good or very good
      statistical correlation of morphometric parameters between the two examined
      nerves. They support the assumption that the sural nerve sufficiently reflects
      the histological changes in other distal sensomotoric nerves. This is valid at
      least in systemic neuropathological diseases and age-dependent processes.

PMID- 11846043
TI  - UV light-induced autofluorescence of full-length Abeta-protein deposits in the
      human brain.
AB  - The formation of amyloid plaques is a hallmark of Alzheimer's disease (AD).
      Amyloid plaques and vascular amyloid deposits in cerebral amyloid angiopathy
      (CAA) consist of the beta-amyloid protein (Abeta) in association with other
      proteins. These Abeta-deposits can be visualized by thioflavin S, Congo red
      staining, silver staining methods and immunohistochemistry. Senile plaques also
      have been shown to exhibit blue autofluorescence. Here we report that UV light
      induced autofluorescence is restricted to full-length Abeta-containing amyloid
      plaques and is also seen in blood vessels affected by CAA. Different types of
      samples from AD and control cortices were examined: native samples, formalin
      fixed paraffin and polyethylene glycol-embedded tissue sections. These samples
      were viewed with a fluorescence microscope under UV light excitation (360 - 370
      nm). By emitting blue fluorescence (>420 nm), amyloid plaques and blood vessels
      affected by CAA were detected in AD and CAA samples. Combination with
      immunofluorescence against anti-Abeta1-42, anti-Abeta17-24, and anti-Abeta8-17
      demonstrated co-localization of the autofluorescent deposits with full-length
      Abeta containing Abeta-deposits. N-terminal truncated Abeta-deposits, such as the
      fleecy amyloid, do not exhibit autofluorescence. In doing so, Abeta
      autofluorescence is a suitable method for screening native tissue samples for
      full-length Abeta-deposits. In contradistinction to conventional and
      immunohistochemical procedures, detection of plaques and CAA by autofluorescence
      enables the recognition of full-length Abeta-deposits in the human brain without
      any chemical interaction whatsoever on the part of Abeta.

PMID- 11846044
TI  - Malignant fibrous histiocytoma associated with a meningothelial meningioma.
AB  - A 72-year-old woman was operated for a left parietal tumor of the meninges. The
      symptomatology began 22 years earlier with a right hemiparesis. The histological
      examination of the tumor showed a proliferation of meningothelial cells with
      whorl formation, associated with a pleomorphic proliferation of a malignant
      fibrous histiocytoma. The meningothelial meningioma showed a typical aspect, with
      nuclear inclusions and absence of mitotic activity. The second tumor component
      showed a storiform architecture with giant multinucleated cells, necrosis and
      many typical and atypical mitoses. There was also an inflammatory component with
      infiltrates of lymphocytes. This tumor component at the border with the
      meningioma appeared to arise from the septa of the meningioma with many prongs
      merging into one large and pleomorphic histiocytomatous tumor. The dual
      histological aspect and the case are discussed in the light of what is already
      known in the literature. The woman has been irradiated after surgery and she is
      doing well 6 months after operation.

PMID- 11846045
TI  - Progesterone receptors are expressed with higher frequency by optic nerve sheath
      meningiomas.
AB  - Optic nerve sheath meningiomas are infrequent neuropathological specimens as
      conservative management of these benign tumors is often adopted. It is
      established that progesterone receptor expression in meningiomas may be of
      functional significance in the growth of these neoplasms and is related to the
      tumor grade and likelihood of recurrence. In addition, progesterone receptor
      expression can be indicative of a potential response of surgically less
      accessible meningiomas to hormonal treatments. We analyzed 30 surgically resected
      optic nerve sheath meningiomas and showed high levels of progesterone receptor
      expression compared to benign meningiomas from other intracranial sites
      suggesting these tumors may be amenable to hormonal therapy.

PMID- 11846047
TI  - Methotrexate in the treatment of ankylosing spondylitis.
AB  - There have been few well-conducted studies into the efficacy of methotrexate in
      Ankylosing spondylitis. The results of a new prospective study in 51 patients are
      presented in this issue but the clinical response was poor. A recurring theme,
      however, is the promising effect noted on peripheral joints compared with that on
      the axial skeleton. Recent histological and magnetic resonance imaging evidence
      suggests that synovitis and subchondral bone marrow changes offer a more rational
      explanation for widespread joint destruction than does enthesitis alone.
      Furthermore, enthesis lesions close to synovial joints occur frequently and may
      be intimately linked with peripheral joint synovitis. At the moment there is no
      hard evidence of efficacy in axial disease, but these observations raise the
      possibility that suppression of synovitis might help in the spine, and that
      enthesitis might respond wherever it is anatomically. Thus further long-term,
      placebo-controlled studies are needed to address specifically the issues of
      enthesitis. spinal symptom relief and the suppression of long-term ankylosis.

PMID- 11846046
TI  - Is stereotactic biopsy a reliable method to differentiate tumor from radiation
      necrosis?
AB  - We report a case of a 37-year-old female who suffered from seizures and underwent
      external beam radiotherapy due to a suspected low-grade astrocytoma in the left
      hemisphere. After 7 years free of seizures under antiepileptic treatment and no
      signs of change in the yearly performed control MRI, she developed a progressive
      right-sided hemiparesis. MRI now showed an enhancing lesion with space occupying
      perifocal edema in the entire left hemisphere. Stereotactic biopsy revealed only
      inflammation. Due to further progress of the neurological deficit an open biopsy
      was performed. Histological examination revealed a middle-graded astrocytoma and
      a radiation necrosis. This case demonstrates that radiation necrosis and tumor
      recurrence may develop concurrently and that it may be difficult to distinguish
      them by clinical or radiological methods.

PMID- 11846048
TI  - Leucocytoclastic vasculitis: an update for the clinician.
AB  - Leucocytoclastic vasculitis is a small vessel inflammatory disease mediated
      mostly by deposition of immune complexes. Infections, medications, chemicals,
      bacteria, viruses, and diseases associated with immune complexes have been
      accused in the pathogenesis. Cutaneous leucocytoclastic vasculitis presents as
      palpable purpura most often localized in the lower extremities, often accompanied
      by abdominal pain, arthralgia and renal involvement. The clinical diagnosis of
      leucocytoclastic vasculitis is confirmed histopathologically by skin biopsy. In
      order to determine the cause of the disease, depending on the patient's history,
      complete blood cell count, blood cultures, cryoglobulins, serum protein
      electrophoresis, rheumatoid factor, antinuclear antibody, and autoantibodies to
      neutrophilic cytoplasmic antigens and complement should be checked. Once the
      diagnosis of leucocytoclastic vasculitis is made, emphasis should be on the
      search for an etiological factor and the identification of the involved organs.
      If possible, the underlying cause should be treated or removed, for example
      discontinuation of drugs. The prognosis depends on the disease that has the
      cutaneous leucocytoclastic angiitis as a component, as well as the severity of
      internal organ involvement. For example, a patient with cutaneous
      leucocytoclastic angiitis and moderate nephritis as component of Henoch-Schonlein
      purpura has a much better prognosis than a patient with these same findings as a
      component of Wegener's granulomatosis. Only if physicians recognize and report
      severe reactions to regulatory authorities and manufacturers, new drugs
      associated with a risk of such reactions can be identified.

PMID- 11846049
TI  - Education in the management of juvenile chronic arthritis. Changes in self
      reported competencies among adolescents and parents of young children.
AB  - OBJECTIVE: The purpose was to evaluate changes in self-reported competencies
      following an education program among parents of children with juvenile chronic
      arthritis (JCA) and among adolescents with JCA. METHODS: The self-reported, 24
      item MEPS questionnaire was used for evaluating the program. Fifty-five parents
      and 11 adolescents completed the questionnaire before, directly after, and four
      months after the eight-hour program. RESULTS: Parents in the education program
      improved significantly concerning their self-reported competencies on medical,
      exercise, pain and social support issues, while the adolescents showed only minor
      improvement. The parents' positive development in some comparisons was also
      significant in relation to that of a non-educated group, whose responses remained
      mainly unchanged over the four months. CONCLUSION: Given the advantages of the
      education program indicated in the study, parent education should be a self
      evident part of the treatment in JCA.

PMID- 11846050
TI  - Quality of life in chronic NSAID users: a comparison of the effect of omeprazole
      and misoprostol.
AB  - OBJECTIVE: To compare the impact on quality of life (QoL) of omeprazole and
      misoprostol during healing, and omeprazole, misoprostol, and placebo during
      maintenance treatment in chronic NSAID users with NSAID-associated gastroduodenal
      lesions. METHODS: Validated baseline and follow-up QoL questionnaires were
      completed by 610 patients (healing: after 4/8 weeks; maintenance: after 6
      months). RESULTS: Patients with arthritis being treated with NSAIDs have a poor
      QoL. Rheumatoid arthritis causes more joint problems and physical mobility
      limitations than osteoarthritis. Chronic NSAID use causes heartburn and
      dyspepsia. QoL improved on both treatments (about equally on two general QOL
      scales), but omeprazole relieved gastrointestinal symptoms more than misoprostol,
      particularly reflux, abdominal pain and indigestion symptoms. During maintenance,
      both treatments maintained QoL, but misoprostol induced diarrhoea. CONCLUSION:
      QoL in arthritis patients on chronic NSAID treatment is destroyed. Omeprazole is
      superior to misoprostol for relief and prevention of NSAID-associated
      gastrointestinal symptoms allowing continued NSAID treatment without compromising
      the patients' QoL.

PMID- 11846051
TI  - Efficacy of methylprednisolone pulse therapy versus infliximab in the treatment
      of severe flares of chronic polyarthritis.
AB  - BACKGROUND: To compare short term efficacy of pulse intravenous (iv)
      Methylprednisolone (MP) versus Infiximab in flares of polyarthritis. PATIENTS
      METHODS: Observational study of consecutive patients admitted with flares of
      chronic polyarthritis. Treatment consisted of three iv doses of MP 1000mg on
      alternate days (MP-group, n = 10) or of Infliximab will be 3 mg/kg at baseline,
      two, and six weeks later (I-group, n=9). DMARD therapy was initiated/continued in
      all patients. Disease parameters at baseline (t=0), two weeks (t=1) and twelve
      weeks (t=2) were compared by non-parametric testing. RESULTS: Reductions in
      disease parameters at both t=1 and t=2, the occurrence of side effects and the
      proportion of patients reaching ACR 20, 50 or 70% response criteria were similar
      in both groups. CONCLUSION: Pulse MP resulted in a symptomatic response similar
      to Infliximab in our patients. The benefit of MP was observed for up to 3 months.

PMID- 11846052
TI  - Hysterectomy and patterns of osteoarthritis. The Ulm Osteoarthritis Study.
AB  - OBJECTIVE: To determine the association between hysterectomy (HE) and patterns of
      osteoarthritis (OA) METHODS: We performed a large cross-sectional study including
      504 female patients admitted for arthroplasty of knee or hip joint. Patients with
      OA were categorized as having bilateral or generalized OA (GOA) according to the
      presence of radiographic OA in the contralateral or different finger joints. Odds
      ratios (OR) and their 95% confidence intervals (CI) for the association between
      HE and OA patterns were estimated adjusting for potential confounders. RESULTS:
      Hysterectomy (HE) was reported by 24.9 percent of the patients. Bilateral OA was
      present in 86.2 percent and GOA was present in 33.3 percent of the patients. HE
      was not associated with bilateral OA (adjusted OR=0.9; 95% CI: 0.5-1.8) but with
      a lower prevalence of GOA (adjusted OR=0.6; CI: 0.3-0.99). CONCLUSION: In
      contrast to earlier studies our results suggest that HE might be a marker for a
      reduced risk for a generalized pattern of OA.

PMID- 11846053
TI  - Aspirin differentially regulates endotoxin-induced IL-12 and TNF-alpha production
      in human dendritic cells.
AB  - OBJECTIVE: In the development of autoimmune diseases, dendritic cells (DC) play
      critical roles. Here, we examined the effect of aspirin on lipopolysaccharide
      (LPS)-induced DC activation. METHODS: The monocyte-derived DC were established.
      The cytokine production was measured by ELISA, reverse transcriptase/polymerase
      chain reaction, or intracellular staining analyzed by flow cytometry. The
      expression of cell surface molecules was determined by flow cytometry. RESULTS:
      Aspirin inhibited LPS-induced DC maturation and costimulatory molecules
      expression. Aspirin, at therapeutic concentrations, also decreased LPS-induced IL
      12 and IL-10 production. In contrast, the LPS-induced TNF-alpha production was
      enhanced by aspirin. The differential effects of aspirin on IL-12 and TNF-alpha
      production may not be due to down-regulation of cyclooxygenase activities.
      CONCLUSION: The various effects of aspirin on LPS-stimulated DC may influence the
      understanding of the diverse immunomodulatory mechanisms of this anti
      inflammatory drug.

PMID- 11846054
TI  - Lower level of education in young adults with arthritis starting in the early
      adulthood.
AB  - An appropriate education may lead to less work disability in patients with
      arthritis. The aim of the study was to determine the educational level in two
      groups of young adults with arthritis. Patients with juvenile arthritis ( JA,
      n=32) and patients with early adult onset of arthritis (EA, n=47) were examined
      with the Quality of Life Scale (QOLS) and a questionnaire concerning education
      and profession counselling. Comparisons with a reference group (n=95) from the
      general population were made. The EA group had lower level of education (p<0.01),
      compared to the reference group. Among the EA patients, 62% had not discussed
      their choice of occupation with anybody, compared to 19% in the JA group. The
      educational level was lower in patients with rheumatic disease starting in early
      adulthood. Educational issues and counselling should be focused on the care of
      young adults with arthritis.

PMID- 11846055
TI  - Samarium-153-EDTMP in the treatment of refractory rheumatoid arthritis.
AB  - We examined the preliminary safety and efficacy of intravenous samarium-153-EDTMP
      (Sm-153) in the treatment of refractory rheumatoid arthritis (RA). In an open
      label sequential group comparison of 0.5, 1.0, and 2.0 mCi/kg, Sm-153 was
      administered as a single intravenous infusion to 24 patients with refractory
      disease. Across treatment doses, the frequency of American College of
      Rheumatology (ACR) 20% responses was 25%, 29%, 25%, and 33% at 2, 4, 8, and 12
      weeks, respectively. Expected significant declines in absolute neutrophil count,
      hemoglobin, and platelet counts were observed with nadirs seen between 2-4 weeks.
      Sm-153, at doses of 0.5 and 1.0 mCi/kg, is well tolerated but minimally effective
      in the treatment of refractory RA as measured using ACR response criteria.

PMID- 11846056
TI  - Possible triggering effect of cytomegalovirus infection on systemic lupus
      erythematosus.
AB  - We report on a patient with systemic lupus erythematosus (SLE) who showed
      elevated titers of IgM antibodies to cytomegalovirus (CMV), suggesting CMV
      infection at the onset of SLE. Serum CMV antigens were also detected in the
      patient. These findings raise the possibility that CMV infection may be related
      to the onset of SLE in certain patients.

PMID- 11846057
TI  - Monarthritis of the ankle as manifestation of a calcaneal metastasis of
      bronchogenic carcinoma.
AB  - We report a case of bronchiogenic carcinoma metastasizing to the calcaneus and
      clinically manifesting itself as a therapy-refractory monarthritis in the right
      ankle. There is a wide spectrum of possible diagnoses of acute ankle monarthritis
      including different forms of inflammatory rheumatic diseases, sarcoidosis,
      osteoarthritis, or septic arthritis. Primary or metastatic malignancies of the
      hand or foot bones are considered to be rare. Persistent monarthritis as a sole
      symptom of a calcaneal metastasis has never been reported. This case demonstrates
      possible difficulties in the early differential diagnosis of acute monarthritis,
      and will be discussed with respect to the few reports on foot acrometastases.

PMID- 11846058
TI  - Measurement of IgM rheumatoid factor by ELISA.

PMID- 11846059
TI  - Surgery for gastric cancer: 10-year experience worldwide.
AB  - To demonstrate recent experience of gastric cancer surgery worldwide and to
      evaluate modern strategies for the treatment of gastric cancer, we investigated
      the English-language literature of the past 10 years, based on papers published
      in well-known medical journals. In many countries, the increased detection of
      early gastric cancer, advanced operative procedures, and careful postoperative
      management have improved the surgical results of gastric cancer over the years.
      Although randomized controlled trials in Europe showed no survival benefit of D2
      resection over D1 resection, the results must be interpreted with caution and
      cannot be extrapolated to Japanese patients, because the morbidity and mortality
      after D2 gastrectomy in Japan are much less than those after D1 gastrectomy in
      Europe. Recently, less invasive treatments, including endoscopic mucosal
      resection and laparoscopic gastrectomy, have become feasible for patients with
      early gastric cancer, but their risks and benefits compared with traditional
      gastrectomy are unclear.

PMID- 11846060
TI  - Adjuvant chemotherapy for gastric cancer: a comprehensive review.
AB  - The role of adjuvant chemotherapy in gastric cancer has been studied extensively
      over the past three decades in an attempt to further improve the prognosis of
      patients with gastric cancer who have undergone curative surgery. To date, no
      definitive conclusions have been drawn from randomized clinical trials of
      adjuvant chemotherapy for gastric cancer, because few studies have shown a
      significant positive impact on survival as compared with surgery alone. The
      negative results of most previous clinical studies do not necessarily mean that
      the adjuvant chemotherapy approach to treatment of gastric cancer does not work.
      Recent published reports of meta-analyses concerning adjuvant chemotherapy of
      gastric cancer revealed small but clear survival advantages for adjuvant therapy
      over surgery alone. The positive data from meta-analyses suggests that there are
      potential survival advantages of adjuvant chemotherapy, but this must be proven
      in the future by well-designed clinical trials that compare adjuvant chemotherapy
      with surgery alone, in which sufficient numbers of patients are enrolled and
      effective chemotherapeutic regimens with appropriate dose intensity are employed.
      Newly developed anticancer agents and/or newer therapeutic combinations or
      strategies (neoadjuvant chemotherapy, chemoradiotherapy, intraperitoneal
      chemotherapy) have the potential to benefit high-risk patients.

PMID- 11846061
TI  - Expression of Cdx1 and Cdx2 mRNAs and relevance of this expression to
      differentiation in human gastrointestinal mucosa--with special emphasis on
      participation in intestinal metaplasia of the human stomach.
AB  - BACKGROUND: The caudal-type homeobox genes, Cdx1 and Cdx2, are candidates for
      directing intestinal development, differentiation, and maintenance of the
      intestinal phenotype. The aims of this study were: (1) to assess the normal
      tissue expression patterns of Cdx1 and Cdx2 in the human gastrointestinal tract
      and (2) to ascertain levels in intestinal metaplasia (IM) of the stomach
      associated with gastritis. METHODS: Fresh human tissues were collected by
      surgical resection from 39 patients after informed consent had been received.
      RNAs were extracted from 11 distinct sites in the gastrointestinal mucosa
      (gastric body, gastric antrum, duodenum, jejunum, ileum, cecum, ascending colon,
      transverse colon, descending colon, sigmoid colon, and rectum), and Northern
      hybridization was performed for Cdr1 and Cdx2 mRNAs. In addition, RNAs were also
      extracted from normal gastric mucosa, and gastric mucosa with mild to severe IM,
      confirmed histopathologically. Reverse-transcriptase polymerase chain reaction
      (RT-PCR) was then carried out for Cdx1 and Cdx2. RESULTS: The expression of Cdx1
      mRNA increased gradually from the duodenum to the distal colon, with no
      expression detected in the stomach. Compared with the distribution of Cdx1 mRNA
      in the mouse gastrointestinal tract, the expression of Cdr1 mRNA in the human
      gastrointestinal tract showed greater predominance in the jejunum and ileum. The
      expression of Cdx2 mRNA increased gradually from the duodenum to the proximal
      colon and decreased from the ascending colon to the rectum. Compared with the
      expression pattern of Cdx2 mRNA in the mouse gastrointestinal tract, the
      expression of Cdx2 mRNA in the human gastrointestinal tract showed greater
      predominance in the ileum. By RT-PCR, both Cdx1 and Cdx2 mRNAs were detected in
      the mild and severe types of IM. However, neither of these mRNAs was identified
      in normal gastric mucosa without IM. CONCLUSIONS: Cdr1 and Cdx2 mRNAs are widely
      present in the human intestinal and colonic mucosae, but not in the gastric
      mucosa, suggesting that their expression may contribute to the intestinal
      phenotype. The high levels of these mRNAs in IM mucosa associated with chronic
      atrophic gastritis point to an association with this phenotypic shift in the
      gastric mucosa.

PMID- 11846062
TI  - Phase II study of sequential high-dose methotrexate and fluorouracil combined
      with doxorubicin as a neoadjuvant chemotherapy for scirrhous gastric cancer.
AB  - BACKGROUND: The prognosis of scirrhous gastric cancer remains poor when it is
      treated with surgical resection alone or chemotherapy alone. A phase II study of
      sequential high-dose methotrexate and fluorouracil, combined with doxorubicin, as
      a neoadjuvant chemotherapy was conducted in an attempt to evaluate the efficacy
      of this regimen in improving the survival of patients with scirrhous gastric
      cancer. METHODS: Patients were eligible if they had potentially resectable
      scirrhous gastric cancer with adequate organ functions and no prior treatment.
      The treatment schedule consisted of methotrexate (1 g/m2, day 1) fluorouracil
      (1.5 g/m2, day 1), leucovorin (15 mg/m2, days 2-4), and doxorubicin (30 mg/m2,
      day 15), repeated at a 28-day interval, and followed by radical surgery. RESULTS:
      A total of 20 eligible patients were registered. Objective responses in the
      neoadjuvant chemotherapy segment were observed in 3 of the 20 (15%) patients. No
      complete remission was observed. The neoadjuvant chemotherapy was associated with
      grade 3 or 4 neutropenia in 14 of the 20 (70%) patients. The median time from the
      initial therapy to the operative day was 82 days. Thirteen of the 20 (65%)
      patients underwent curative resection. No treatment-related deaths occurred.
      However, the 2-year survival rate in this treatment program (25%) did not show
      any superiority over that in historical controls. CONCLUSIONS: Sequential high
      dose methotrexate and fluorouracil, combined, with doxorubicin, as a neoadjuvant
      chemotherapy for scirrhous gastric cancer did not improve the survival rate in
      spite of improving the curative resection rate.

PMID- 11846063
TI  - Expression of Fas and Fas ligand in human gastric adenomas and intestinal-type
      carcinomas: correlation with proliferation and apoptosis.
AB  - BACKGROUND: Fas (APO-1/CD95), a member of the tumor necrosis factor/nerve growth
      factor receptor superfamily, mediates apoptosis in response to agonistic
      antibodies or Fas ligand (FasL) binding. Previous reports indicated an up
      regulation of FasL in gastric carcinomas to evade host immune attack. Fas/FasL
      expression, however, has not been analyzed in terms of apoptosis and
      proliferation in gastric adenoma and carcinoma. METHODS: This study was conducted
      on seven human gastric carcinoma cell lines, 47 gastric adenomas, and 75
      intestinal-type adenocarcinomas (48 early and 27 advanced carcinomas). Fas/FasL
      expression was examined by immunohistochemistry, apoptosis by the terminal
      deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick-end labeling (TUNEL)
      method, and Fas gene mutation by a reverse transcriptase (RT) polymerase chain
      reaction-single-strand conformation polymorphism (PCR-SSCP) and sequencing
      method. RESULTS: Fas and FasL expressions were noted in 18 (38.3%) and 17 (36.2%)
      adenomas, in 21 (43.8%) and 33 (68.8%) early carcinomas, and in 10 (37.0%) and 19
      (70.4%) advanced carcinomas, respectively. The frequency of FasL expression was
      significantly higher in advanced carcinomas than in the early carcinomas and
      adenomas; in contrast, there was no significant difference in Fas expression
      among the three groups. The mean apoptotic index (AI) was 4.96+/-0.51 in the
      adenomas, 2.96+/-0.23 in the early carcinomas, and 1.67+/-0.17 in the advanced
      carcinomas. A significantly higher Al was noted in the lesions with Fas
      expression than in those without Fas expression in all three groups. No missense
      mutations of the Fas gene were detected in any of the gastric carcinoma cell
      lines, or in the gastric adenomas or carcinomas. CONCLUSIONS: Upregulation of
      FasL may correlate with the progression of gastric carcinoma. Apoptosis in
      gastric adenoma and carcinoma cells may occur via Fas-dependent and -independent
      pathways, but further clarification is needed.

PMID- 11846065
TI  - Sequential methotrexate and 5-fluorouracil therapy for gastric cancer patients
      with peritoneal dissemination: a retrospective study.
AB  - BACKGROUND: Most gastric cancer patients with peritoneal dissemination have been
      excluded from clinical studies because they usually have no measurable lesions.
      They also have a high risk of toxicity because of complications such as
      intestinal obstruction and ascites. We conducted a retrospective analysis to
      evaluate the efficacy and feasibility of sequential methotrexate (MTX) and 5
      flurorouracil (5FU) therapy for this population. METHODS: This analysis was based
      on 56 consecutive chemotherapy-naive patients with confirmed peritoneal
      dissemination of gastric cancer who were being treated with sequential MTX/5FU.
      The therapy comprised a weekly schedule of MTX 100 mg/m2, given as a bolus
      infusion 3 h prior to a bolus infusion of 5FU 600 mg/m2. Leucovorin 10mg/m2 was
      administered six times, every 6h, starting 24h after MTX administration. RESULTS:
      Evidence of peritoneal dissemination was confirmed by laparotomy in 16 patients,
      by cytologic examination of ascites in 11 patients, and by clinical imaging in 29
      patients (15 with ascites, 13 with intestinal obstruction; in 10 of the 29
      patients, detection was by barium enema or computed tomography [CT] scan).
      Neutropenia of grade 3 or worse and anemia were observed in 8 (14%) and 10 (18%)
      of the 56 patients, respectively. There was one treatment-related death due to
      neutropenic sepsis. Of the 26 patients with measurable lesions, 9 showed a
      response (36%). The median survival time and median time to treatment failure
      were 259 days and 167 days, respectively. Objective improvement of ascites was
      seen in 13 of 26 patients (50%), including 5 with showed complete disappearance
      of ascites. Seven of the 15 patients (47%) with intestinal obstruction showed
      resolution, and 8 of the 21 patients (38%) who needed nutritional support before
      the treatment were free of that support for a median duration of 220 days after
      the completion of the treatment. Forty-seven of the 56 patients (84%) could be
      treated at outpatient clinics. CONCLUSIONS: This regimen may be of clinical
      benefit for patients with peritoneal dissemination of gastric cancer.

PMID- 11846064
TI  - Combined resection of invaded organs in patients with T4 gastric carcinoma.
AB  - BACKGROUND: To understand the efficacy of gastrectomy combined with the resection
      of other organs and to refine the indications for this type of surgery, the
      records of 156 patients with carcinoma of the stomach directly invading adjacent
      organs or structures (T4 gastric carcinoma) were analyzed retrospectively.
      METHODS: The patients were divided into three groups, as follows: in group A,
      curative resection was performed by the combined resection of invaded organs or
      structures; in group B, although combined resection was performed, curative
      resection could not be performed because of the extent of lymph node metastasis,
      liver metastasis, and/or peritoneal metastasis; in group C, combined resection
      was not performed. RESULTS: In patients with peritoneal or liver metastasis,
      there was no significant difference in prognosis among the three groups. In
      patients without peritoneal and liver metastasis, the prognosis of group A was
      significantly better than that of group B or group C, irrespective of the extent
      of lymph node metastasis or the number of invaded organs. In these group A
      patients, the 5-year survival rates of those with localized tumors and no lymph
      node metastasis, those with localized tumors and lymph node metastasis, those
      with infiltrating tumors and no lymph node metastasis, and those with
      infiltrating tumors and lymph node metastasis were 100%, 56.2%, 57.1%, and 13.6%,
      respectively. CONCLUSIONS: Combined resection of involved organs should be
      carried out with curative intent in patients with localized gastric cancer or
      infiltrating gastric cancer without lymph node metastasis.

PMID- 11846066
TI  - Gastric cancer in Singapore.

PMID- 11846067
TI  - Mucinous gastric carcinoma: is it more malignant?

PMID- 11846068
TI  - Macrophyte and periphyton dynamics in a UK Cretaceous Chalk stream: the river
      Kennet, a tributary of the Thames.
AB  - An initial study to observe the seasonal trends and to determine the factors
      influencing macrophyte and periphyton growth patterns was undertaken on a
      representative reach of the River Kennet (UK) over a 2-year period (1998-2000).
      Maximum average macrophyte and average periphyton dry matter biomass recorded
      during the growing season were 200 and 21 g m(-2), respectively. The
      relationships between macrophyte and periphyton percentage cover and biomass data
      with physico-chemical variables were investigated. Regression analysis indicated
      that of the parameters measured, flow, and in the case of the dominant Ranunculus
      spp., solar radiation, were best able to predict macrophyte biomass and cover.
      The periphytic biomass within the reach was low, possibly as a result of
      relatively high flows and low phosphorus concentrations following the
      introduction of effluent treatment at the sewage works immediately upstream of
      the reach. Periphytic biomass was poorly correlated with the physical variables
      measured. This indicates that biomass is regulated by complex interactions
      between the physical and chemical factors, such as flow, solar radiation and
      phosphorus concentration. These interrelationships require further investigation.

PMID- 11846069
TI  - Regulation of surface water quality in a Cretaceous Chalk catchment, UK: an
      assessment of the relative importance of instream and wetland processes.
AB  - To investigate the relative importance of instream nutrient spiralling and
      wetland transformation processes on surface water quality, total nitrogen (TN)
      and total phosphorus (TP) concentrations in a 200-m reach of the River Lambourn
      in the south-east of England were monitored over a 2-year period. In addition,
      the soil pore water nutrient dynamics in a riparian ecosystem adjacent to the
      river were investigated. Analysis of variance indicated that TN, TP and suspended
      sediment concentrations recorded upstream of the wetland were statistically
      significantly higher (P < 0.05) than those downstream of the site. Such results
      suggest that the wetland was performing a nutrient retention function. Indeed,
      analysis of soil pore waters within the site show that up to 85% of TN and 70% of
      TP was removed from water flowing through the wetland during baseflow conditions,
      thus supporting the theory that the wetland played an important role in the
      regulation of surface water quality at the site. However, the small variations
      observed (0.034 mg TN l(-1) and 0.031 mg P l(-1)) are consistent with the theory
      of nutrient spiralling suggesting that both instream and wetland retention
      processes have a causal effect on surface water quality.

PMID- 11846070
TI  - Phosphorus sources, speciation and dynamics in the lowland eutrophic River
      Kennet, UK.
AB  - This paper examines the behaviour of phosphorus (P) in a lowland chalk
      (Cretaceous-age) stream, the upper River Kennet in southern England, which has
      been subject to P remediation by tertiary treatment at the major sewage treatment
      works in the area. The effects of treatment are examined in relation to boron, a
      conservative tracer of sewage effluent and in terms of the relative contributions
      of soluble reactive phosphorus (SRP) loads from point and diffuse sources, and in
      stream SRP loads. These results indicate a baseline reduction in in-stream SRP
      concentrations immediately following P-treatment of approximately 72%. Subsequent
      high flows result in a greater contribution of diffuse inputs and increases in
      SRP levels relative to the initial post-treatment period. The dynamics of SRP and
      particulate phosphorus (PP) are examined under a wide range of river flow
      conditions. Given the flashy nature of near-surface runoff in the River Kennet,
      sub-weekly (daily automated) sampling was used to examine the dynamics in SRP and
      PP concentrations in response to storm events. Simple empirical models linking
      weekly SRP concentrations with flow were developed. The empirical models were
      successfully applied to the daily data, to partition TP measurements and provide
      an estimate of daily SRP and PP concentrations. Mass balance studies were used to
      examine net gains and losses along the experimental river reach and indicate
      large net losses (up to 60%) during the extreme low flows and high SRP
      concentrations prior to P-treatment, which may be linked to extensive epiphytic
      growth. Phosphorus dynamics and response to P-treatment are discussed in relation
      to hydrological controls in permeable chalk catchments and wider implications for
      eutrophication management are examined.

PMID- 11846071
TI  - Diurnal and longer term patterns in carbon dioxide and calcite saturation for the
      River Kennet, south-eastern England.
AB  - Continuous pH, dissolved oxygen and temperature information for three sites on
      the upper portion of the River Kennet, a tributary of the Thames in southern
      England is presented. A thermodynamic model is developed which links this
      information to weekly water quality data allowing the estimation of dissolved
      carbon dioxide and calcite saturation levels within the river on a continuous
      basis. The results show a dynamic and variable system along the length of the
      river. Marked diurnal patterns are observed for pH, dissolved oxygen, dissolved
      carbon dioxide and calcite saturation and the highest fluctuations occur during
      the summer months. There is also a marked gradient downstream in average pH (7.5
      8.0) and dissolved carbon dioxide (30-10 times atmospheric pressure). Dissolved
      oxygen levels average approximately 100% saturation across all sites, and the
      diurnal pattern occurring during the summer months declines downstream. The
      waters are permanently oversaturated with respect to calcite and the diurnal
      patterns of change are maximal during the summer months. The results are
      discussed in relation to: (a) the balance between photosynthesis and respiratory
      processes; (b) the relative interchanges between the sediment/plant interface
      with the water column; and (c) the rates of degassing of carbon dioxide and
      oxygen between the river surface and the atmosphere.

PMID- 11846072
TI  - The phosphorus budget of the Thame catchment, Oxfordshire, UK: 1. Mass balance.
AB  - The relative magnitudes of annual diffuse and point source loads of phosphorus
      (P) to the River Thame were estimated from daily and monthly measurements of
      discharge and concentration. Existing data from gauging and monitoring sites on
      the river network and at point sources were supplemented by survey data at a
      range of spatial scales. Results showed that during low flow periods most of the
      P could be attributed to point sources, while at high flows the figure was less
      than 10%. The introduction of P stripping at Aylesbury, a major sewage treatment
      works in the catchment, was estimated to have reduced the annual load of P from
      the sewage treatment works by approximately 45 t, with a similar reduction in
      loss from the catchment. This gave a reduction in low flow concentrations of
      soluble reactive phosphorus (SRP) from 2.5 to 1.7 mg l(-1). Concentrations of SRP
      in river water remain above eutrophication thresholds because of the influence of
      other STWs in the catchment and insufficient natural discharge to dilute this.

PMID- 11846073
TI  - Phosphorus in rivers--ecology and management.
AB  - This paper examines the nature of the risk to riverine ecosystems from
      artificially enhanced loads of phosphorus, considers the key sources of
      phosphorus enrichment and ways of controlling them, and provides a framework for
      developing control strategies. The aquatic plant community is the foundation for
      a healthy and diverse riverine ecosystem, providing food, shelter and breeding
      habitats for a wide range of animal species. Phosphorus enrichment in rivers can
      degrade the plant community by altering the competitive balance between different
      aquatic plant species, including both higher plants and algae. This has
      consequences for the whole ecosystem. To promote healthy riverine plant
      communities and the wide range of animal species dependent on them, phosphorus
      concentrations need to be reduced to as near to background levels as possible.
      The risk of adverse effects declines as phosphorus concentrations approach
      background levels, such that any incremental reduction should be seen as a
      positive step towards trophic restoration. Pragmatic management targets vary
      between 0.02 and 0.1 mg(-1) soluble reactive phosphorus, depending on river type,
      with an interim target of 0.2 mg(-1) for heavily enriched rivers. Continuous
      point sources of phosphorus, dominated by sewage treatment works, have a highly
      important influence on levels of bioavailable phosphorus in the water column
      through the growing season. It is important to tackle point sources
      comprehensively so that reductions in phosphorus concentrations are maximised
      during this critical time of year. Diffuse sources of phosphorus, particularly
      from agriculture, are a major contributor to phosphorus levels in riverine
      sediments, where it can be utilised by benthic algae and rooted plants. This
      phosphorus can also be released into the water column by a variety of processes.
      As point sources are brought under control, the relative contribution from
      diffuse sources becomes increasingly important. An integrated programme of
      control, involving proactive action on both point and diffuse sources, will be
      required in most circumstances to bring phosphorus levels in the water column and
      sediment down to near background levels.

PMID- 11846074
TI  - Patterns in nutrient concentrations and biological quality indices across the
      upper Thames river basin, UK.
AB  - This paper examines the nutrient chemistry and biological quality indices [Mean
      Trophic Rank (MTR) and Trophic Diatom Index (TDI)] for rivers within the upper
      Thames basin. The predominant sources of nitrogen within the rivers monitored
      were diffuse and agricultural in nature. However, phosphorus showed both diffuse
      and point source signals. MTR surveys undertaken both upstream and downstream of
      major STWs indicate that these rivers are 'at risk' of eutrophication or 'badly
      damaged'. MTR surveys also indicate increased trophic status downstream of STWs,
      whereas TDI does not indicate such a consistent pattern. Phosphorus treatment at
      selected major sewage treatment works in the upper Thames basin resulted in
      significant reductions in in-stream P concentrations and reductions in fluxes by
      a half to two thirds. However, the effects of P-reduction on in-stream ecology
      (measured as MTR and TDI) were more difficult to ascribe, owing to: (1) the high
      variability in river flow rates experienced since P-reduction was introduced; (2)
      lag effects related to P stores in river bed sediments; and (3) diffuse and
      smaller point source inputs upstream. The results of this study indicate that
      control of upstream sources of phosphorus may prove critical in improving the
      biological quality status of UK lowland rivers, including ecological responses to
      P-source controls on the major sewage treatment works downstream. Upstream
      sources include both diffuse (agricultural) sources and small point source inputs
      which, at present, are not classified as 'qualifying discharges' under the Urban
      Wastewater Treatment Directive (UWWTD) and are thus not subject to phosphorus
      control measures. These results are of relevance for integrated, sustainable
      management and protection of European freshwater resources, particularly in terms
      of new ecological targets for water quality management under the new Water
      Framework Directive.

PMID- 11846075
TI  - Phosphorus-calcium carbonate saturation relationships in a lowland chalk river
      impacted by sewage inputs and phosphorus remediation: an assessment of phosphorus
      self-cleansing mechanisms in natural waters.
AB  - The relationship between calcium carbonate saturation and phosphorus
      concentrations for seven sites on the upper reaches of the River Kennet are
      examined. The findings are related to issues of groundwater supplies and the
      introduction of phosphorus treatment of effluent from the Marlborough sewage
      treatment works (STW) at part of the way along the study reach. Being supplied
      from a Cretaceous Chalk aquifer, the Kennet is mainly of a calcium-bicarbonate
      type and has a relatively constant composition of many major water quality
      determinands. Typically, the waters average a pH of approximately eight (range
      approx. 7.5-8.5) during the day with the lowest values occurring at the upstream
      site. Dissolved carbon dioxide varies from approximately 5 to 35 times
      atmospheric pressure during the late morning with the highest values occurring at
      the upstream site. However, in-stream biological activity gives rise to marked
      diurnal fluctuations in pH and dissolved carbon dioxide concentrations and during
      the summer months, by mid to late afternoon, pH is at its maximum and dissolved
      carbon dioxide is at its lowest: this is shown by continuous measurements at one
      of the river sites. Alkalinity and calcium concentrations remain relatively
      constant at approximately 4,700 microEq/l (range 3,500-6,000 microEq/l) and 120
      mg/l (range 85-150 mg/l), respectively, and the waters are oversaturated with
      respect to calcium carbonate (calcite) typically by a factor of six (range 2-25).
      Along the reach, soluble reactive phosphate (SRP) increases from the first to the
      second site with the introduction of sewage supplies from the Marlborough STW,
      and then declines further downstream as sewage dilution and uptake by the river
      bed/aquatic plants increases. The differences in concentration decrease after
      phosphorus removal from Marlborough STW. Despite this change, there is no clear
      indication of any calcite solubility control except perhaps at times of extreme
      baseflow during the growing season when within-stream photosynthesis is maximal
      and within-stream residence times are longer. A comparison of river and
      groundwater data shows that the groundwaters have similar alkalinities and
      calcium concentrations. However, the groundwaters have (a) higher carbon dioxide
      saturations (a factor of 2-5 times the value for the river), (b) lower pHs (0.5
      1.5 units), (c) lower SRP concentrations (a quarter or less of the river values)
      and (d) waters near calcite saturation (unlike the surface waters which are
      oversaturated). The findings indicate a river system dominated by the input
      carbon dioxide laden groundwaters in approximate equilibrium with calcite
      attenuated by within-channel biological and physical processes. Within the river:
      (a) the waters degas carbon dioxide increasing the pH, producing oversaturated
      conditions; and (b) oscillating pH-dissolved carbon dioxide levels occur between
      day and night due to changing balances between photosynthesis and respiration. It
      seems that lowering the phosphorus levels have not resulted in calcite
      precipitation within the water column and that no significant within-stream self
      cleansing mechanisms are occurring that might be predicted from theory: other
      components in the water such as dissolved organic carbon may inhibit calcite
      nucleation. However, the low SRP levels in the groundwater coupled with calcite
      saturation, may well indicate that phosphorous concentrations within the
      groundwater are regulated by such processes: the number of calcite nucleating
      sites are orders of magnitude higher and the calcite inhibitors may be less
      prevalent.

PMID- 11846076
TI  - Calcite saturation in eastern UK rivers.
AB  - Calcite saturation in eastern UK rivers is assessed in relation to the potential
      kinetic inhibition of calcite precipitation. Two well established inhibitors are
      considered: soluble reactive phosphorus (SRP, i.e. inorganic monomeric
      phosphorus); and dissolved organic carbon (DOC). The rivers show a range of
      calcite saturation levels from approximately 1hundredth to approximately 100
      fold. The greatest range occurs for the northernmost river considered, the Tweed,
      where the waters range from highly unsaturated to highly oversaturated. The
      lowest range occurs for the most southerly rivers (the Great Ouse and the Thames)
      where the waters are consistently oversaturated with respect to calcite. The
      contrasting patterns relate to a greater diversity of water quality within the
      northern regions. Thus, during the winter, the main waters are derived from the
      upland areas with acidic soils and low weathering rates. During the summer
      baseflow periods, groundwater inputs are more important and high photosynthesis
      results in particularly high pHs and calcite oversaturation. In contrast, for the
      southern rivers, the main source of water during both the summer baseflow and the
      winter highflow periods comes from calcium carbonate rich aquifer sources.
      Statistical analysis of pH vs. the logarithm of the calcite saturation index for
      each river indicates strong linear features with individual gradients of
      approximately 1. This linearity results from an autocorrelation (the logarithm of
      the saturation index is calculated from the pH) and this indicates that calcite
      solubility controls are not operative in any of the rivers examined. A comparison
      of calcite saturation levels and SRP and DOC concentrations show a pattern
      inconsistent with kinetic hindrance, although some structure is observed,
      probably due to the mixing reactions between point and diffuse sources of water
      with contrasting chemistry.

PMID- 11846077
TI  - Calcite saturation in the River Dee, NE Scotland.
AB  - The spatial and temporal variations in calcite (calcium carbonate) solubility
      within the Dee basin of NE Scotland were assessed using water chemistry data
      gathered from a network of 59 sites monitored for water quality from June 1996 to
      May 1997. Calcite solubility, expressed in terms of a saturation index
      (SIcalcite), was determined from measured streamwater pH, Gran alkalinity and
      calcium concentrations and water temperature. In general, the waters of the Dee
      system are undersaturated with respect to calcite, though the saturation index is
      higher during the summer months indicating a dependency on flow conditions and
      biological activity. Under low-flow conditions, the streamwaters are dominated by
      water derived from the lower soil horizons and deeper groundwater stores and
      therefore, ions such as Gran alkalinity and calcium are at their highest
      concentrations as they are derived mainly from bedrock weathering. The influence
      of biological activity on the carbonate system is also evident as the observed pH
      and estimated EpCO2 values indicate strong seasonal patterns, with the highest pH
      and lowest EpCO2 values occurring during the summer low-flow periods. Only at
      three sites in the lowland region of the catchment, during the summer low-flow
      period, are the waters oversaturated. As such, the Dee system represents an
      extreme 'end-member' case when compared to many UK rivers that span both under-
      and oversaturated conditions during the year. Regression analysis highlights a
      systematic change in the SIcalcite-pH relationship in a broad east-west direction
      across the Dee system. At sites draining the relatively impermeable upland areas,
      the regression of SIcalcite against pH gives a straight line with a gradient in
      the range 1.6-2.4. Correspondingly, under the most extreme alkaline conditions
      found at sites draining lowland agricultural areas, a straight-line relationship
      exists but with a gradient of unity. It is concluded that these changes in the
      SIcalcite-pH relationship are due to variations in the bicarbonate system induced
      by the flow conditions and biological activity. Given the waters are
      undersaturated, then calcite precipitation and hence phosphorus co-precipitation
      cannot occur within the water column.

PMID- 11846078
TI  - Total phosphorus content of river sediments in relationship to calcium, iron and
      organic matter concentrations.
AB  - Data on the total concentrations of phosphorus, calcium, iron and organic matter
      in surface bed-sediments taken from rivers in the Thames catchment (Wey,
      Blackwater, Thame and Kennet), the River Swale in Yorkshire (data excludes the
      organic matter content) as well as the headwaters of the Great Ouse, are collated
      and compared. Total concentrations of phosphorus, iron and calcium range from 1.7
      649, 12-8,333 and 9-4,605 micromol g(-1) (dry weight), respectively, with organic
      matter in the range of 0.6-19% by dry weight. For the Wey, Blackwater and Great
      Ouse, sewage inflows had no detectable effect on the sediment concentrations of
      total calcium, iron and organic matter whereas for the Blackwater and Great Ouse,
      the total phosphorus contents of the sediment were higher downstream of the
      effluent input in comparison with a less impacted upstream location.
      Relationships between the total phosphorus content of the sediments and contents
      of iron, calcium and organic matter indicated marked differences between the
      rivers. Although the organic matter content of the sediments was found to be a
      significant predictor for the total phosphorus concentration for the Blackwater
      and Great Ouse, the total iron content was also useful for the Blackwater and
      total calcium for the Great Ouse. It is postulated that this difference is a
      result of the sediment processes that are known to occur in these two systems,
      i.e. co-precipitation of phosphate with calcite in the Great Ouse and the
      formation of vivianite in anoxic sediments of the Blackwater.

PMID- 11846079
TI  - Phosphorus uptake into algal biofilms in a lowland chalk river.
AB  - This paper examines the growth and uptake of phosphorus into algal biofilms in
      the River Kennet, a lowland chalk (Cretaceous-age) stream in southern England.
      Algal biofilms were grown on artificial plastic substrates (templates) placed (i)
      on the riverbed and (ii) within the mid-water column. Experiments were set up to
      examine differences in growth rates of newly colonising biofilms compared with
      biofilms left to accumulate for periods of up to 6 months. Rates of algal biofilm
      production were measured by the chlorophyll a concentration that had accumulated
      per cm2 over the number of days that the biofilm template had been immersed in
      the river water. An algal biofilm bloom occurred in early spring, prior to peak
      suspended chlorophyll a concentrations within the water column. Biofilm samples
      collected in February and March had the highest chlorophyll a and total
      phosphorus concentrations. The biofilm bloom corresponded with increased solar
      radiation and declining river flow conditions. Periodic increases in soluble
      reactive phosphorus concentrations in the overlying river water did not
      correspond with any significant increase in biofilm production. These results
      suggest that light, rather than phosphorus is a key factor for biofilm growth in
      the River Kennet. Higher rates of chlorophyll a development in mid-water column
      biofilms may be linked to greater light exposure; however, maximum total-P
      concentrations were similar for both bed and water column biofilms. Newly
      colonising biofilms exhibited higher chlorophyll a and total-P concentrations
      than biofilms left to accumulate over longer terms, suggesting that fresh
      substrate availability promotes high rates of biofilm growth. Both 'condensed and
      organic' P (stored in biomass) and 'inorganic' (mineral) P fractions within the
      biofilms were present in varying proportions, although the early spring biofilm
      bloom resulted in maximum proportions and absolute concentrations of 'condensed
      and organic' P. Calcite was the only crystalline mineral detected within the
      biofilms. Ratios of Ca:inorganic P are largely consistent with the presence of
      CaCO3-P co-precipitates, although one very low value suggested that there may
      also be additional sources of inorganic P, possibly P adsorbed to clays or
      organics within the biofilm. However, poor linkages between CaCO3 and inorganic P
      concentrations suggest that, although the inorganic P fraction within the biofilm
      may be derived largely from CaCO3-P co-precipitation, the subsequent processes
      controlling overall CaCO3 and inorganic P concentrations in the biofilm are
      complex.

PMID- 11846080
TI  - On modelling the flow controls on macrophyte and epiphyte dynamics in a lowland
      permeable catchment: the River Kennet, southern England.
AB  - A new in-stream model of phosphorus (P) and macrophyte dynamics, the Kennet
      Model, was applied to a reach of the River Kennet to investigate the impacts of
      changing flow conditions on macrophyte growth. The investigation was based on the
      assessment of two flow change scenarios, which both included the simulation of
      decreasing total phosphorus concentrations from a sewage treatment works due to
      improved effluent treatment. In the first scenario, the precipitation and
      potential evaporation outputs from a climate change model (HadCM2 GGx) where
      input into the catchment model INCA to predict the mean daily flows in the reach.
      In the second scenario, the mean daily flows observed in a historically dry year
      were repeated as input to the in-stream model to simulate an extended low flow
      period over 2 years. The simulation results suggest that changes in the seasonal
      distribution of flow were not detrimental to macrophyte growth. However, the
      simulation of extended periods of low flow suggests that a proliferation of
      epiphytic algae occurs, even when the in-stream phosphorus concentrations are
      reduced due to effluent treatment. This epiphytic growth was predicted to reduce
      the macrophyte peak biomass within the reach by approximately 80%. Thus, the
      model simulations suggest that flow was more important in controlling the
      macrophyte biomass in the River Kennet, than the in-stream phosphorus
      concentrations, which are elevated due to agricultural diffuse sources.

PMID- 11846081
TI  - On modelling the impacts of phosphorus stripping at sewage works on in-stream
      phosphorus and macrophyte/epiphyte dynamics: a case study for the River Kennet.
AB  - A new model of in-stream phosphorus and macrophyte dynamics, 'The Kennet model',
      was applied to a reach of the River Kennet, southern England. The reach, which is
      1.5 km long, is immediately downstream of Marlborough sewage treatment works,
      where phosphorus reduction by tertiary effluent treatment began in September
      1997. The model is used to simulate the flow, water chemistry and macrophyte
      biomass within the reach, both before and after phosphorus removal from the
      effluent. Monte Carlo experiments coupled with a general sensitivity analysis
      indicate that the model offers a feasible explanation for the salient aspects of
      the system behaviour. Model simulations indicate that epiphyte smothering is an
      important limitation to macrophyte growth, and that higher stream and pore water
      soluble reactive phosphorus (SRP) concentrations allow the earlier onset of
      growth for the epiphytes and macrophytes, respectively. Higher flow conditions
      are shown to reduce the simulated peak epiphyte biomass; though at present, the
      effect of flow on the macrophyte biomass is unclear. Another simulation result
      suggests that phosphorus will not be released from the bed sediments in this
      reach following phosphorus removal from the effluent.

PMID- 11846082
TI  - Steady state and dynamic modelling of nitrogen in the River Kennet: impacts of
      land use change since the 1930s.
AB  - Steady state and dynamic models have been developed and applied to the River
      Kennet system. Annual nitrogen exports from the land surface to the river have
      been estimated based on land use from the 1930s and the 1990s. Long term modelled
      trends indicate that there has been a large increase in nitrogen transport into
      the river system driven by increased fertiliser application associated with
      increased cereal production, increased population and increased livestock levels.
      The dynamic model INCA (Integrated Nitrogen in Catchments) has been applied to
      simulate the day-to-day transport of N from the terrestrial ecosystem to the
      riverine environment. This process-based model generates spatial and temporal
      data and reproduces the observed instream concentrations. Applying the model to
      current land use and 1930s land use indicates that there has been a major shift
      in the short term dynamics since the 1930s, with increased river and groundwater
      concentrations caused by both non-point source pollution from agriculture and
      point source discharges.

PMID- 11846083
TI  - The phosphorus budget of the Thame catchment, Oxfordshire: 2. Modelling.
AB  - The phosphorus budget of the River Thame was modelled at a daily time scale,
      using estimates of diffuse and point source contributions of discharge. The model
      simulated suspended sediment (SS), soluble unreactive phosphorus (SUP), soluble
      reactive phosphorus (SRP) and particulate phosphorus (PP) concentrations within
      the main river and major tributaries. Diffuse source estimates of phosphorus
      loads were based on characteristic losses from identified main landscape classes,
      with hydrology described by a simple conceptual storage model. In-stream flow was
      modelled using a kinematic wave equation. Transfer of suspended sediment and
      phosphorus components was approximated by advection. In-stream sources and sinks
      included uptake and release of soluble reactive phosphorus by bed sediment,
      instant equilibration between SRP and the PP concentration on suspended sediment,
      and flow-related entrainment and deposition of suspended sediment. Simulations at
      sites within the catchment were compared with measurements made in 1998-1999.
      Results showed the P budget is dominated by mixing of diffuse and point source
      water, but some within-river processes have been shown to be capable of
      significantly influencing SRP concentrations. The development of a sediment
      entrainment and deposition component of the model has proved particularly
      valuable in emulating the hysteretic relationship between discharge and suspended
      sediment concentration in the river. It also provides a measure of available bed
      sediment.

PMID- 11846084
TI  - Application of a model to predict cyanobacterial growth patterns in response to
      climatic change at Farmoor reservoir, Oxfordshire, UK.
AB  - The cyanobacterial growth for the next 90 years at Farmoor Reservoir, Oxfordshire
      is predicted using the cyanobacterial growth model, CLAMM, with data obtained
      from HADCM2 climate change model. It is predicted that solar radiation at the
      water-body surface will decrease slightly due to increased cloud cover.
      Predictions of cyanobacterial growth indicate little change in total production
      although the main summer growing season may be extended. It is also suggested
      that increased wind velocities may affect the frequency of 'blooming incidents'.

PMID- 11846085
TI  - Water quality functioning of lowland permeable catchments: inferences from an
      intensive study of the RIVER KENNEt and upper River Thames.
AB  - This paper brings together information on the water quality functioning of the
      River Kennet and other parts of the upper River Thames in the south east of
      England. The Kennet represents a groundwater fed riverine environment impacted by
      agricultural and sewage sources of nutrient pollution. Descriptions of the
      general water quality of the area, nutrient sources, sinks and within river
      processes are provided together with biological responses to driving issues of
      agriculture, sewage treatment and climatic change. Models are developed and
      applied to assess the key processes involved for a highly dynamic system and to
      provide initial estimates of the likely responses to environmental change.
      Furthermore, the economic aspects of pollution control are reviewed, together
      with legislation issues, which are presented within the context of a landmark
      case known as the 'Axford Inquiry', the implications of which extend to regional
      and national dimensions. The paper concludes with a discussion on the present
      state of knowledge, key issues and future research on the science and management
      of groundwater fed nutrient impacted riverine systems.

PMID- 11846086
TI  - An economic approach to reducing water pollution: point and diffuse sources.
AB  - A review of economic policy towards pollution control is presented which shows
      that appropriate measures will depend on whether the pollution is of a point or a
      diffuse nature. Regulation of the former is comparatively straightforward, with
      command and control and market instruments the tools of pollution control. The
      advantages and disadvantages of each measure are outlined. However, the inability
      to monitor emissions at source, precludes the application of point source
      measures in the case of diffuse source pollution. Instead, methods are required
      which overcome the need for direct monitoring. Several suggestions that propose
      ways of achieving this have been put forward and these are described. It is
      concluded that appropriate measures depend on the particular features of the
      problem and it is not possible to offer a blanket solution to either point
      sources or diffuse pollution.

PMID- 11846087
TI  - Controls on the discharge of Chalk streams of the Berkshire Downs, UK.
AB  - The water quality and biological functioning of major UK rivers draining
      permeable basins cannot be fully understood without knowledge of the spatial and
      temporal controls on the aquifer-river system. In this paper, hydrogeological
      features of Chalk streams feeding the Thames, the focus of this special issue,
      are described. Large-scale features, such as line sinks along the Thames and
      major tributaries such as the Kennet, tend to determine the regional groundwater
      flow patterns in the Chalk aquifer, whereas the complex characteristics of the
      Chalk dominate the local spatial and temporal patterns of groundwater discharge
      to the tributaries draining the dip slopes. These different controls are
      described and illustrated by particular reference to the Lambourn (a sub
      catchment of the Kennet) and Pang catchments. Various issues requiring further
      investigation are also highlighted.

PMID- 11846088
TI  - Recovery from acidification in the Tillingbourne catchment, southern England:
      catchment description and preliminary results.
AB  - Measurements of acid deposition and streamwater chemistry made in 1979-1982 and
      1999-2000 are compared for a small, acid-sensitive catchment in Southeast
      England. The location, geology, soils, vegetation and hydrology of the catchment
      are described. The catchment is located on an acidic cretaceous sandstone with a
      low permeability clay sub-stratum. Soils are predominantly podzol and gley, with
      some mesotrophic peat. The catchment is forested. Mean volume-weighted
      concentrations in precipitation have changed approximately in proportion to
      emission changes. SO4(2-) has declined by 61%, H+ by 75%, both NO- and NH4+ by
      37% and Cl- by 26%. Changes in wet deposition are greater, sulfate deposition
      declined by 69%, non-marine SO4(2-) by 73%, H+ deposition by 75%, NO3- and NH4+
      by 50% and Cl- by 41%. Sulfate deposition in throughfall, a surrogate for total
      deposition measurement, has declined by 82% and non-marine SO4(2-) by 86%. Some
      of these changes are due to alterations in the tree cover and location of the
      collectors. In 1979-1982, the flux of NO3- and NH4+ in throughfall was less than
      in rainfall, 7.5 compared with 11.3 kg N ha(-1) year(-1), showing that N uptake
      by the canopy was greater than dry deposition of these species. However, in 1999
      2000, the throughfall flux of N was greater than rainfall, 19.6 compared to 5.7
      kg N ha year(-1), indicating that canopy uptake is not occurring to the same
      extent. Surface water was sampled at the same locations in the catchment during
      the two periods. At the catchment exit, mean pH increased, from 3.93 to 4.21 mg
      l(-1), and SO4(2-) declined from 20.2 to 16.7 mg l(-1) (18%). The decrease in
      SO4(2-) is much less than the reduction in deposition, suggesting that the
      predicted recovery is being delayed by release of sulfur from the soil. In
      contrast, NO3- concentrations in the catchment waters increased from 0.22 to 0.52
      mg N l(-1) (133%) despite the reduction in N deposition. NH4+ concentrations were
      low during both study periods. It is concluded that recovery from acidification
      is probably occurring, but is possibly being delayed by desorption of soil S. The
      catchment is also showing signs of increasing N saturation, despite a reduction
      in N inputs.

PMID- 11846089
TI  - Interception and attenuation of atmospheric pollution in a lowland ash forested
      site, Old Pond Close, Northamptonshire, UK.
AB  - A study of interception of chemicals at an ash plantation forest in southern
      central England shows the modification of acidic pollution as it passes from
      precipitation, through the vegetation cover and the soil to generate surface
      runoff. Precipitation is highly acidic (pH 3.7-4.8, alkalinity -16 to -200
      microEq/l) and it is enriched in the strong acid anions associated with
      acidification (sulfate and nitrate) as well as ammonium and the trace elements
      aluminium and zinc. The concentration of both sea-salt and pollutant components
      varies considerably over time and this is linked to washout from the atmosphere
      during precipitation events as marked by an inverse relationship between
      concentration and volume of catch. The catchment is also supplied by sea-salt and
      pollutant additions as dry deposition: gaseous inputs of SO(x) may also increase
      sulfate deposition. Through the vegetation, much of the acidity is neutralised
      and, particularly during the growth period, calcium, magnesium and potassium is
      cycled, while sodium and nitrate are partially removed. Within the catchment,
      weathering ensures that further base cation production occurs leading to enhanced
      neutralisation of acidity and the generation of positive alkalinities. As a
      result, surface runoff becomes buffered with alkalinity approximately 490
      microEq/l and pH approximately 7.9. Thus, although the acidification input from
      the atmosphere is high, this does not translate to acidic runoff due to within
      canopy and within-soil processes.

PMID- 11846091
TI  - Early activation of hepatic stellate cells and perisinusoidal extracellular
      matrix changes during ex vivo pig liver perfusion.
AB  - In previous works, we observed during liver transplantation procedure, the early
      activation of hepatic stellate cells (HSC) which acquire alpha-smooth muscle (SM)
      actin expression. In this study, we evaluated changes in HSC and in
      perisinusoidal extracellular matrix during ex vivo pig liver perfusion. Under
      general anesthesia, pig livers were flushed and removed, and then perfused ex
      vivo for 6 h with homologous blood. Liver biopsies were taken before and after
      washout, at 5 min perfusion, and then hourly. Tissues were processed for
      immunohistochemistry, immunofluorescence, confocal microscopy, in situ
      hybridization and electron microscopy. Before and after liver washout, alpha-SM
      actin was present in vessel walls but in very few lobular HSC. After 1 h
      perfusion, a strong reactivity for alpha-SM actin was present in HSC,
      particularly along dilated sinusoids. At the ultrastructural level, numerous
      microfilament bundles appeared in HSC cytoplasmic processes. During perfusion,
      type I and type IV collagens, type III procollagen, and fibronectin acquired a
      looser organisation in relation with the enlargement of perisinusoidal spaces;
      laminin appeared in perisinusoidal spaces around portal areas and fibrillin
      deposits increased. In situ hybridization studies showed an increase of the type
      I procollagen mRNA expression mainly in portal tracts and septa. Ex vivo liver
      perfusion induces: 1) an early activation of HSC which acquire the expression of
      alpha-SM actin, and 2) significant changes in the perisinusoidal extracellular
      matrix. These results are compatible with the view that HSC function as liver
      specific pericytes participating in the regulation of sinusoidal blood pressure.

PMID- 11846090
TI  - Cathepsin B and complement C3 are major comigrants in the estrogen-induced
      peroxidase fraction of rat uterine fluid.
AB  - The luminal fluid of estrogen or DES-stimulated uterus of immature rats contains
      10-12 isoforms of peroxidase between pI 4.5-6.0. N-terminal amino acid sequencing
      of diaminobenzidine-peroxidase bands eluted from IEF and SDS-PAGE gels showed the
      presence of cathepsin B and the complement family of proteins as the major
      comigrants. Sequential treatment of uterine fluid by cation, anion, and size
      exclusion chromatography resulted in a five-fold purification of peroxidase
      having a specific activity of 273 units/mg. Mass spectrometric studies of bands
      isolated from SDS-PAGE gels from the size-exclusion purified peroxidase fraction
      showed the presence of complement C3 along with novel previously uncharacterized
      proteins. Two dimensional electrophoresis followed by N-terminal amino acid
      sequencing confirmed the presence of cathepsin B isoforms and isoforms of a novel
      protein at approximately 87 kDa. Identification by mass spectrometry from the
      database for this novel protein was inconclusive but could most likely be a
      candidate for estrogen-induced peroxidase. Results conclusively prove that
      cathepsin B and complement C3 are major proteins in the estrogen-induced
      peroxidase fraction of uterine fluid.

PMID- 11846092
TI  - One case of immunotactoid glomerulopathy: morphological-ultrastructural aspects.
AB  - Starting from a group of 736 renal biopsy patients, evaluated by ultrastructural
      studies over a period of 22 years, the authors present a rare case of
      immunotactoid glomerulopathy, suggesting that these forms, until a few years ago
      considered in the same group as fibrillary glomerulonephritis, are in fact a
      separate entity; moreover, they may represent a very early manifestation of
      plasmacellular dyscrasia still at the initial stage.

PMID- 11846093
TI  - Cyclooxygenase-2 immunoreactivity in the ischemic neonatal human brain. An
      autopsy study.
AB  - Cyclooxygenase-2 (COX-2) is known to be expressed in rat brain and up-regulated
      by ischemia. The administration of COX inhibitors before as well as soon after
      the ischemic insult reduces the extension of cerebral damage in rats.
      Overexpression of COX-2 has also been shown in the ischemic brain of adult human
      patients, while no information concerning COX-2 expression in neonatal ischemia
      is available. Intrapartum asphyxia and perinatal brain injury may result in
      cerebral palsy, mental retardation or epilepsy. COX-2 expression in the brain of
      neonates delivered after severe birth asphyxia was investigated using
      immunohistochemistry. Meningeal vessel walls of term and preterm babies widely
      expressed COX-2 immunoreactivity, as did periventricular large vessels in
      preterms. A number of brain cells (mature and immature cortical, periventricular
      and basal ganglia neurons, and oligodendrocytes of the cerebral white matter in
      brains from term neonates) also expressed COX-2. The present findings suggest
      that COX-2 may take part in enhancing neonatal brain damage via different
      mechanisms, such as those involving excitotoxicity and production of reactive
      oxygen species.

PMID- 11846094
TI  - Immunocytochemical localization of NOVH protein and ultrastructural
      characteristics of NCI-H295R cells.
AB  - In this study we present biochemical and immunocytochemical results on NOVH
      protein secretion and localization in NCI-H295R cells, as well as results on the
      ultrastructural characteristics of NCI-H295R cells. NCI-H295R cells were
      characterized by small quantities of rough and smooth endoplasmic reticulum, many
      free ribosomes, large nuclei with prominent nucleoli, numerous elongated
      mitochondria, a few Golgi complexes, and a small number of lipid droplets. Large
      numbers of coated pits and coated vesicles were present, but no secretory
      granules or exocytotic profiles were seen. Best ultrastructural preservation of
      NCI-H295R cells was achieved when fixation was done directly on the culture
      dishes and the cells were detached by scraping. Our biochemical results showed
      that NCI-H295R cells secreted large amounts of NOVH protein. The
      immunocytochemical localization of NOVH protein showed that the protein was
      localized in the cytoplasm, the plasma membrane and the nuclear envelope. This
      localization pattern, along with the ultrastructural and biochemical findings
      raise interesting questions on the function(s) and the mode of secretion of NOVH
      protein.

PMID- 11846096
TI  - Ultrastructural differentiation of cardiomyocytes of the zebrafish during the 8
      26-somite stages.
AB  - We report cellular hypertrophy, mitochondrial proliferation and differentiation,
      myofibrillogenesis, and junctional maturation in cardiac progenitor cells between
      the 8 and 26-somite stages of the zebrafish, Danio rerio. However, coordinated
      contraction in embryonic cardiomyocytes did not occur until 26-somite stage when
      'developed' intercalated discs, rooted sarcomeres, and a well-established
      sarcoplasmic reticulum had differentiated.

PMID- 11846095
TI  - Developmental effects of lead acetate on the chick embryo metanephros.
AB  - The developmental effects of lead acetate were studied in the chick embryo
      metanephros, the third renal rudiment that acquires morphological characteristics
      of functioning kidney already during the prenatal life. Lead exposure was
      obtained by applying a lead acetate solution on the chick embryo chorioallantoic
      membrane at the days 9, 10 and 11 of incubation. Quantitative evaluation of the
      lead concentration assessed by furnace atomic absorption spectrophotometry at the
      days 14 and 21 of incubation demonstrated metal presence both in the
      chorioallantoic membrane (CAM) and in metanephros (MN). The lead concentration
      was higher in CAM than in MN; the metal amount was similar in the CAM of 14 and
      21 day embryos, but significantly higher in the 14day embryo MN than in the 21
      day embryo MN. Morphological observations on metanephros tissue of control and
      lead-treated embryos were performed under light, electron transmission and
      electron scanning microscopes. Peculiar attention was devoted to the expression
      of the junctional protein connexin 43, the major component of the gap junctions
      in the renal cells. The results indicated that lead treatment does not intervene
      in the general differentiation of the metanephric nephrons. The lead is
      reabsorbed by the proximal tubule cells that are engulfed by endocytotic vacuoles
      and metal deposits and show long term degenerative changes. Expression of Cx43
      protein and ultrastructure of gap junctions between proximal tubule cells
      appeared to be unchanged. The morphological aspects of the MN corpuscles and
      tubules agree with the suggestion of a lead cytotoxic effect but do not
      corroborate, at least in this experimental model, the view of primary damage
      exerted by lead on the gap junctions of the renal epithelial cells.

PMID- 11846097
TI  - Field emission scanning electron microscopy and freeze-fracture transmission
      electron microscopy of mouse cerebellar synaptic contacts.
AB  - Samples of albino mice were processed by the cryofracture method for scanning
      electron microscopy and examined with the field emission scanning electron
      microscope (FESEM). Freeze-etching direct replicas of mice cerebellar cortex were
      also studied with the transmission electron microscope (FFTEM), as a
      complementary technique for obtaining higher resolution, three-dimensional
      correlative images of cerebellar synaptic contacts. At the granular, Purkinje
      cells and molecular layers, the cryofracture method for FESEM selectively removed
      the neuroglial cell investment, facilitating the visualization of the outer and
      inner surfaces of cerebellar synaptic contacts. In addition, FFTEM showed the
      real extension of perisynaptic neuroglial investment. The outer surface of mossy
      fiber rosettes and their digitiform processes were seen at the granular layer,
      making flat and invaginated synaptic contacts with the granule cell dendrites. At
      the molecular layer, the longitudinal traject of parallel fibers or nonsynaptic
      segments and their synaptic varicosities were characterized. These latter
      established synaptic contacts with Purkinje dendritic spines. Fractured parallel
      fiber endings showed the SE-I images of clustered spheroidal synaptic vesicles
      and mitochondria and the surrounding cotton-like appearance of Bergmann glial
      cell cytoplasm. Climbing fibers showed a characteristic crossing-over bifurcation
      pattern in the white matter and in the three-layer structure of cerebellar
      cortex, formation of tendril collaterals in the granular layer, topographical
      relationship with Purkinje cell soma and retrograde collaterals in the molecular
      layer. The climbing fiber synaptic relationship with Purkinje dendritic spines
      was characterized, by means of FFTEM, by the presence of large synaptic endings
      and aggregation of intramembrane particles at the P and E faces of presynaptic
      endings, characteristic of excitatory synapses.

PMID- 11846098
TI  - Noncanonical structural-functional organization of nucleoli in maturing oocytes
      of sea urchin Paracentrotus lividus.
AB  - The dynamics of structural and functional organization of the nucleolus in the
      oocytes of P. lividus is described. At the late stages of oogenesis the nucleolus
      is composed of two main components, namely the peripheral zone (PZ) and the
      central zone (CZ) which are spatially separated. This two-component structure of
      the nucleolus is formed, at early stages of oogenesis, by stepwise segregation of
      the fibro-granular component and by its migration to the nucleolar periphery.
      Absence of morphologically distinct fibrillar centers and dense fibrillar
      component in nucleoli of both somatic cells and oocytes makes it possible to
      classify the nucleoli of P. lividus as 'noncanonical' type. Based on detailed
      morphological and cytochemical analysis the following molecular interpretation of
      nucleolar ultrastructure in oocytes of P. lividus is proposed: 1) the PZ,
      containing RNP-positive granules 15 nm in size, but lacking Ag-NOR proteins and
      BrU incorporation, can be considered a structural equivalent of the granular
      component of 'typical' nucleoli; 2) the CZ, which is the site of incorporation of
      RNA precursors, contains intranuclear DNA, RNP-fibers and accumulates Ag-NOR
      proteins, corresponds to both FC and DFC of 'typical' nucleoli; 3) nucleolar
      growth during oogenesis, leading to the 1000-fold increase of nucleolar volume,
      seems to be correlated with the stockpiling of nonfunctioning mature preribosomal
      particles which will be utilized during embryogenesis.

PMID- 11846099
TI  - Sequential pictorial presentation of neural interaction in the retina. 1. The
      synaptic ribbon complex.
AB  - The analysis of circuits in the retina revealed by three-dimensional
      reconstructions (Sjostrand, 1958, 1974, 1976,1978, 1990) is presented in a
      simplified way by series of schematic drawings illustrating each individual step
      in the sequence of synaptic transmission between the neurones. In addition, the
      analysis has been extended further compared to earlier presentation (Sjostrand,
      1998a). The circuit of the synaptic ribbon complex controls transmission between
      cones and bipolar cells by the inhibitory input from horizontal cells being
      controlled by the cone. At low light intensity, horizontal cell inhibition blocks
      transmission between cones and bipolar cells because of high concentration of
      transmitter at the critical synapse, explaining fading of cone vision. The
      requirement for maintaining a low transmitter concentration at the synapses to
      secure proportionality between input and output signals is established by
      horizontal cell inhibitory input both at the cone-bipolar cell and the cone
      horizontal cell synapses. How one bipolar cell can transmit information regarding
      average light intensity over a large area of the retina is discussed in detail.

PMID- 11846100
TI  - Newly identified 'wanderer' cells in the dicyemid mesozoan Kantharella
      antarctica: a new mode of reproduction?
AB  - In the nematogen of the dicyemid mesozoan Kantharella antarctica two types of
      germinal cells are present which differ in size and composition of their
      organelles: the voluminous type A germinal cells, with high amounts of glycogen,
      small vesicles and a cortically arranged cytoskeleton, which differentiate into
      migratory 'wanderer' cells and the small type B germinal cells, with polarly
      arranged bundles of microtubules, which develop asexually into vermiform embryos.
      Type A germinal cell, however, becomes polarized during its differentiation,
      whereby the nucleus and all remaining organelles concentrate at one pole and the
      cytoskeleton organizes into a pseudopod at the other. Now called 'wanderer' cell,
      it leaves the nematogen by opening the junctions along the contact zones of
      neighbouring cells using this intercellular space like an excretory duct. This
      polarized migratory cell exhibits conspicuous morphological features that are
      similar to mature sperm of nematodes, whereby the characteristics of the
      cytoskeleton resemble that of amoeboid Protozoa.

PMID- 11846101
TI  - The ultrastructure of spermatozoa of the slender catfish Silurus microdorsalis
      (Teleostei, Siluriformes, Siluridae) with phylogenetic considerations.
AB  - The spermatozoa of the slender catfish Silurus microdorsalis examined using
      transmission and scanning electron microscopy are characterized by a tubular
      structure and the absence of axonemal fins. Their characteristics can be
      considered to represent a valid symplesiomorphy uniting the Siluridae and taxon
      specific for this family. The tubules of Silurus spermatozoon are not observed in
      the other siluroids. Unusual tubules occur in Citharinus spermatozoa of
      Characiformes. In addition, there is a considerable similarity in the absence of
      axonemal fins between Siluridae and Characiformes. Thus the two shared
      characteristics provide strong evidence that there exists a phylogenetic link
      between Characiformes and Siluriformes. Silurus appears to be plesiomorphic in
      having lost the axonemal fins while retaining the tubules in midpiece. The
      spermatozoa of S. microdorsalis are similar to those of other siluroids having a
      spherical head with a deep nuclear fossa, a short midpiece and an elongated tail.
      However, there are some differences between Silurus and other siluroids in the
      orientation of the centrioles, the number of the mitochondria and the axonemal
      fins, and minor differences between S. microdorsalis and S. asotus, in particular
      the orientation of the centriolar complex, and the arrangement of the tubules and
      the mitochondria in the midpiece. The deep nuclear fossa represents a
      synapomorphy uniting the Siluriformes, while the shallow nuclear fossa and the
      absence of axonemal fins are shared by two orders, Characiformes and
      Cypriniformes.

PMID- 11846102
TI  - Do microtubules around the Toxoplasma gondii-containing parasitophorous vacuole
      in skeletal muscle cells form a barrier for the phagolysosomal fusion?
AB  - The intracellular fate of Toxoplasma gondii was studied in primary cultures of
      skeletal muscle cells (SMC). The labelling of secondary lysosomes with BSA-Au
      particles showed no phagolysosomal fusion with the vacuole containing the
      parasite. After internalization of the parasites, the parasitophorous vacuole
      became involved by closely apposed endoplasmic reticulum (ER) and mitochondria;
      within 18 h of interaction, microtubules were visualized in association with the
      parasitophorous vacuole, suggesting that they could form a barrier for the
      phagolysosomal fusion.

PMID- 11846103
TI  - An intent of correlating clinical manifestations and ultrastructural lung changes
      in mice inoculated with Tityus discrepans (Buthidae) venom.
AB  - Investigation of the pathogenesis of human pulmonary damage caused by the toxic
      aggression by Tityus discrepans venom relies to a considerable extent upon the
      use of animal models. In this work, authors examine the correlation of clinical
      manifestations and changes in the organisation of cellular and subcellular
      pulmonary components in the murine model that probably resembles the damage found
      in envenomed humans. To evaluate lung subcellular response to Tityus discrepans
      venom, male C57/Bl adult mice were randomised into two groups: envenomed mice
      were intraperitoneally injected at a dose of 5 mg/Kg of weight and controls
      received saline solution. Lung samples were processed by electronic microscopy
      techniques and observed in a Hitachi-300. Ultrastructural findings in pulmonary
      tissue showed a partial denudation of its epithelial cells; the basal membrane
      was irregular and swollen. In the interstice there were fibroblasts with multiple
      cytoplasmatic projections and abundant extracellular material. Adjacent to the
      interstice bronchiolar areas with cells showing disperse nuclear chromatin were
      appreciated. There were losses of the intercellular unions and a clear separation
      among the cellular plasmatic membranes was observed. In conclusion, we suggest
      that some of the clinical manifestations of scorpion envenoming may be determined
      by ultrastructural lung damage produced by toxins present in this venom.

PMID- 11846104
TI  - Morphology and migratory behavior of bovine pulmonary artery endothelial cells
      and C6 astrocytoma cells in a three-dimensional type I collagen matrix.
AB  - The purpose of this investigation was to compare the morphological
      characteristics and migratory behavior of bovine pulmonary artery endothelial
      cells (PAE) and C6 astrocytoma cells in a three-dimensional type I collagen
      matrix. Samples of both cell types were cultured and prepared for scanning
      electron microscopy and time-lapse video photomicrography using standard
      protocols. Observations included comparative analyses of factors such as the
      state of the matrix, the presence of cell processes and the distribution of cells
      throughout the sample. Results revealed that PAE cells formed a monolayer and
      were connected by many cytoplasmic extensions. They were distributed evenly
      throughout the collagen matrix and they migrated slowly. In contrast, C6
      astrocytoma cells aggregated into clumps and digested the matrix while migrating
      through it quite rapidly. Photomicrography also revealed the presence of
      filopodia and invadopodia in the PAE samples and astrocytoma samples
      respectively. These cytoplasmic processes may function in either cell-cell
      communication or cell motility. This study demonstrates that endothelial cells
      and C6 astrocytoma cells behave very differently when grown in type I collagen
      matrices. Future studies include finding ways to slow tumor metastasis by
      inhibiting migration through various matrices or to slow tumor growth by
      preventing endothelial cell migration and angiogenesis.

PMID- 11846105
TI  - Testicular ultrastructure and morphology of the seminal pathway in Prochilodus
      scrofa.
AB  - The seminiferous tubules of Prochilodus scrofa present a coiled morphological
      arrangement with intertubular anastomoses and unrestricted spermatogonial
      distribution. The structural pattern of the seminiferous tubules is cystic, with
      cysts formed by cytoplasmic prolongations of Sertoli cells. Inside the cysts are
      observed different types of germ cells. The seminiferous tubules open
      individually on the ventral surface of the main testicular duct present in each
      testis. Each main testicular duct prolongs as a spermatic duct, fusing with the
      spermatic duct of the opposite side to form the common spermatic duct which opens
      into the urogenital papilla. The mature sperm cysts break and extravasate their
      content into the lumen of the seminiferous tubules from which the seminal fluid
      and the spermatozoa penetrate the main testicular duct, the spermatic duct and
      the common spermatic duct for semen ejaculation.

PMID- 11846106
TI  - International relations: broadening our perspectives.

PMID- 11846107
TI  - How to develop a service learning program in dietetics education.

PMID- 11846108
TI  - Can you judge a bar by its wrapper?

PMID- 11846109
TI  - Understanding and negotiating access contracts with insurers and complementary
      networks.

PMID- 11846110
TI  - Disease management, registered dietitians and medical nutrition therapy.

PMID- 11846111
TI  - The chemical senses and nutrition in aging: challenging old assumptions.

PMID- 11846112
TI  - Dietetics students' low knowledge, attitudes, and work preferences toward older
      adults indicate need for improved education about aging.
AB  - OBJECTIVE: This study examined students' knowledge and attitudes about aging and
      their interest in working with the older adult population in the United States.
      DESIGN: A 97-item questionnaire included demographic items, a ranking section on
      work preferences by age groups, and two validated scales: the Palmore Facts on
      Aging Quiz, and the Oberleder Attitude Scale. SUBJECTS: Those surveyed were
      enrolled in the 10 largest universities in the 5 states with the largest
      population of older adults: California, Florida, New York, Texas, and
      Pennsylvania. Of 555 questionnaires that program directors requested for their
      class(es), 299 completed questionnaires were returned. This 54% return rate was
      affected by program directors requesting more questionnaires than needed. Of the
      299 dietetics/nutrition students who completed the survey, 65% were in the 18 to
      22 year age range, 91% were women, 81% were non-Hispanic white, and 81% were
      seniors in college. STATISTICAL ANALYSES: Pearson's correlation was applied to
      test for relationships between knowledge and attitudes; t tests for differences
      in knowledge, attitudes, and work preferences by age, gender, and experience with
      older adults; and Tukey's multiple comparison test for differences in knowledge,
      attitudes, and work preferences by state. RESULTS: Students had low knowledge
      about aging (Palmore, mean percent correct +/- standard deviation = 40.1%+/
      13.0%) and neutral attitudes toward older adults (Oberleder, mean score = 69.1+/
      8.2). When asked which of 10 age groups they preferred to work with, respondents
      ranked the 3 oldest age groups (65 to 74, 75 to 84, 85 and older) lowest on
      average (6.0, 7.3, 8.6, respectively). APPLICATIONS/CONCLUSIONS: More didactic
      instruction about aging and more positive experiences with older adults through
      fieldwork may be needed to prepare future practitioners to provide nutrition
      services to this increasing population segment.

PMID- 11846113
TI  - Nutrition fact sheet. Potatoes: positively nutritious!

PMID- 11846114
TI  - Nutrient intake and body weight in a large HIV cohort that includes women and
      minorities.
AB  - OBJECTIVE: Evaluate the baseline nutrient intake of an HIV positive population
      that includes significant representation from women and minorities, and determine
      the relationship between state of disease and nutritional intake. DESIGN:
      Baseline data from a prospective study (Nutrition for Healthy Living). SUBJECTS:
      Individuals with HIV in the Boston and Rhode Island area (n = 516); 25% were
      women and 30% were minorities. METHODS: Nutrient intakes from 3-day food records,
      which included vitamin/mineral supplements, were estimated by gender and nonwhite
      vs white categories, after grouping by CD4 lymphocyte counts. STATISTICAL
      ANALYSES: Spearman correlation coefficients, Wilcoxon signed rank test, Wilcoxon
      rank sum test, chi2 test, and restricted cubic spline model were used for data
      analyses as indicated. RESULTS: Macronutrient but not micronutrient intake was
      statistically and inversely associated with decreasing CD4 cell counts. The
      median intake of micronutrients was higher in the study sample compared with the
      same age and gender group in NHANES III data; however, 25% to 35% of the women in
      our study sample had dietary intakes of less than 75% of the DRIs for vitamins A,
      C, E and B-6, and iron and zinc. White men had statistically higher values of all
      micronutrients compared with nonwhite men. Body mass index for men and women
      ranged from 23 to 25. CONCLUSIONS/APPLICATIONS: Median values for micronutrient
      intake from food plus vitamin/mineral supplements were adequate in the overall
      population studied, but a large percent of women and minorities had inadequate
      nutrient intakes and would benefit from dietary assessment and counseling.

PMID- 11846115
TI  - Cognitive research enhances accuracy of food frequency questionnaire reports:
      results of an experimental validation study.
AB  - OBJECTIVE: To test whether changing a food frequency questionnaire (FFQ) on the
      basis of cognitive theory and testing results in greater accuracy. Accuracy was
      examined for 4 design issues: a) Grouping: asking about foods in a single vs
      multiple separate questions; b) different forms of a food: asking consumption
      frequency of each form of a food (eg, skim, 2%, whole milk) vs a nesting approach
      -asking frequency of the main food (eg, milk) and proportion of times each form
      was consumed; c) additions (eg, sugar to coffee): asking independent of the main
      food vs nested under the main foods; d) units: asking frequency and portion size
      vs frequency of units (eg, cups of coffee). DESIGN: Participants in two randomly
      assigned groups completed 30 consecutive daily food reports (DFRs), followed by 1
      of 2 FFQs that asked about foods consumed in the past month. One was a new,
      cognitively-based National Cancer Institute (NCI) Diet History Questionnaire; the
      other was the 1992 NCI-Block Health Habits and History Questionnaire.
      SUBJECTS/SETTING: 623 participants, age range 25 to 70 years, from metropolitan
      Washington, DC. Statistical analyses performed Accuracy was assessed by comparing
      DFR and FFQ responses using categorical (percent agreement) and continuous (rank
      order correlation, discrepancy scores) agreement statistics. RESULTS: Grouping:
      accuracy was greater using separate questions. Different forms of food: accuracy
      was greater using nesting. Additions: neither approach was consistently superior;
      accuracy of the addition report was affected by accuracy of the main food report.
      Units: both approaches were similarly accurate. CONCLUSIONS: Accuracy of FFQ
      reporting can be improved by restructuring questions based on cognitive theory
      and testing.

PMID- 11846116
TI  - Efficiency of breakfast consumption patterns of ninth graders: nutrient-to-cost
      comparisons.
AB  - OBJECTIVE: To assess the efficiency of breakfast consumption patterns in terms of
      nutrient-to-cost comparisons. DESIGN: Twenty-four-hour dietary recalls were
      collected and food items named were priced (prices from local grocery stores and
      restaurants were averaged). Three breakfast consumption groups were identified:
      restaurant foods (fast foods), ready-to-eat (RTE) cereal, and other foods.
      SUBJECTS: Subjects consisted of 567 ninth-grade students (57% female, 86% white,
      mean age 14.8 years) in New Orleans, La. STATISTICAL ANALYSES: Analysis of
      variance techniques were used to test statistical significance for total nutrient
      intake levels, intake levels of nutrients per 1,000 kcal, and nutrient intake
      levels per dollar spent. Groupings were determined using the Duncan test or
      pairwise comparisons. RESULTS: Five percent of students ate a fast-food
      breakfast, 30% ate RTE cereal, and 65% ate other breakfasts. The mean cost of the
      breakfast meals was significantly (P<.0001) higher for the fast-food breakfast
      than for the RTE cereal breakfast and the other breakfast (fast>other=RTE). For
      every dollar spent, the RTE cereal and other breakfasts provided significantly
      more energy, carbohydrate, fiber, sugar, and protein than the fast-food
      breakfast. The other breakfast provided significantly (P<.001) more total and
      saturated fat per dollar than the fast-food or RTE cereal breakfasts. The RTE
      cereal breakfast provided significantly (P<.001) more, per dollar spent, of folic
      acid, iron, niacin, vitamins A and D, and zinc than the other 2 breakfast meals.
      APPLICATIONS: The importance consumers place on taste, cost, and convenience
      continues to influence types of foods consumed. Yet, their food choices may not
      be as efficient in terms of the nutrients obtained per dollar spent. With the
      increasing demands being placed on families and the decreasing amount of time
      being spent on food preparation, nutrition education programs should continue to
      promote a higher level of efficient food choices.

PMID- 11846117
TI  - The elderly nutrition program: an effective national framework for preventive
      nutrition interventions.
AB  - OBJECTIVE: To guide national policy, Congress mandated the 1992 research
      evaluation of the Elderly Nutrition Program (ENP), the nation's oldest framework
      for providing community- and home-based preventive nutrition and health-related
      services to older persons. This article summarizes key findings on the program's
      influence on nutritional health, the targeting and costs of its nutrition
      services, and the study's policy implications. DESIGN: The research included a
      nationally representative sample of ambulatory and homebound ENP participants And
      a matched sample of nonparticipants drawn from the US Health Care Financing
      Administration's Medicare beneficiary listings. Interviews conducted in
      respondents' homes considered demographic and health characteristics and assessed
      anthropometry and physical functioning, nutrient intake and socialization
      patterns, and utilization of ENP program services (participants only).
      Administrative and service delivery data were gathered from all levels of the ENP
      infrastructure. RESULTS: The ENP program currently provides congregate and home
      delivered meals and other nutrition- and health-related services to about 7% of
      the older population overall, including an estimated 20% of the nation's poor
      elders. Compared with nonparticipants, ambulatory and homebound ENP participants
      are better nourished (4% to 31% higher mean daily nutrient intakes; P<.001) and
      achieve higher levels of socialization (17% higher average monthly social
      contacts; P<.001). Federal spending on ENP nutrition services is efficiently
      leveraged by funding from other public and private sources, allowing ENP to more
      than double the nutrition services it provides to program participants.
      CONCLUSIONS: ENP is a well-targeted, effective, and efficient federal program
      available to dietetics and other professionals for providing elderly persons with
      community-based and home-delivered nutrition and related services. The ENP
      infrastructure offers a potential model for preventive nutrition intervention
      programs in ambulatory and homebound at-risk older populations.

PMID- 11846118
TI  - Macrosomia in neonates of mothers with gestational diabetes is associated with
      body mass index and previous gestational diabetes.

PMID- 11846119
TI  - Intake of calcium and vitamin D in 3 Canadian long-term care facilities.

PMID- 11846120
TI  - Energy intake must be increased among recently hospitalized patients with chronic
      obstructive pulmonary disease to improve nutritional status.

PMID- 11846121
TI  - Visual observation is a valid means of assessing dietary consumption among older
      adults with cognitive deficits in long-term care settings.

PMID- 11846122
TI  - Nutrient content of school meals in elementary schools on American Indian
      reservations.

PMID- 11846123
TI  - Evaluating school-based interventions using the Healthy Eating Index.

PMID- 11846124
TI  - Position of the American Dietetic Association: food and nutrition misinformation.
AB  - It is the position of the American Dietetic Association that food and nutrition
      misinformation can have harmful effects on the health and economic status of
      consumers. It is the role of nationally credentialed dietetics professionals to
      advocate for and promote sound, science-based nutrition information to the
      public, function as primary nutrition educators to health professionals, and
      actively counter and correct food and nutrition misinformation. The federal
      government has recognized the strong link between nutrition and health in recent
      years. Consumers are taking greater responsibility for self-care and are hungry
      for food and nutrition information, creating opportunities for nutrition
      misinformation, health fraud, and quackery to flourish. The media are consumers'
      leading source of nutrition information, but news reports rarely provide enough
      context for consumers to interpret the advice given. Promoters turn preliminary
      findings into sales pitches with baseless claims, often for the sole purpose of
      economic gain. Effective nutrition communication is consumer focused and
      presented with sufficient context to allow consumers to weigh the information and
      determine whether it applies to his or her unique needs. Nationally credentialed
      dietetics professionals are best prepared to communicate sound advice and
      scientific advances about nutrition. These dietetics professionals have a
      responsibility to take an active role in providing accurate, easily understood
      food and nutrition information, interpreting emerging research for media and
      consumers and encouraging consumers to look for credentialed dietetics
      professionals as nutrition experts.

PMID- 11846125
TI  - Telemedicine: legal, ethical, and liability considerations.

PMID- 11846126
TI  - 2000 Commission on Dietetic Registration Dietetics Practice Audit.

PMID- 11846127
TI  - USDA's Economic Research Service supports nutrition and health outcomes research.

PMID- 11846128
TI  - Optimal pool size and window period.

PMID- 11846129
TI  - Troponin I concentrations of shed blood might influence monitoring of myocardial
      injury after coronary operations.
AB  - In a prospective study we evaluated the concentration of cardiac troponin I
      (cTnI) and creatine kinase activities (CK) in shed mediastinal blood in the early
      postoperative period after coronary artery bypass grafting (CABG). Forty seven
      patients who underwent first time elective CABG were studied. CTnI levels and CK
      activities in arterial blood and shed mediastinal blood were measured after
      admission to the intensive care unit (ICU) and 6 h after unclamping the aorta.
      Mediastinal shed blood samples were drawn from 23 patients (group A) before the
      filter of the cardiotomy reservoir and from 24 patients (group B) behind.
      Additionally, both markers were measured in blood samples collected from the cell
      saver. There were no significant differences between both groups (A and B) with
      regard to perioperative parameters. Mean loss of mediastinal shed blood in all
      patients was 207 +/- 127 ml within the first 6 h after operation. There was a
      positive correlation between CK activities and cTnI concentrations in serum and
      mediastinal shed blood, but shed blood contained significantly higher
      concentrations of cTnI as well as CK activities than the circulating blood after
      admission to the ICU and 6 h after unclamping the aorta. At both time points the
      cTnI-concentrations and CK activities in shed blood in group B were lower than
      those in group A but much higher than in serum. The effects of the use of a blood
      filter diminishes with time. Mediastinal shed blood contains extremely high cTnI
      concentrations and CK activities. Retransfusion of higher quantities of shed
      blood might lead to false-positive diagnosis of perioperative myocardial
      infarction.

PMID- 11846130
TI  - Post-transfusion alloimmunization to granulocytes and platelets in Japanese
      patients as determined by the MPHA method.
AB  - The current occurrence of alloimmunization to granulocytes and platelets after
      blood transfusion is unclear due to the fact that antibody assays are cumbersome.
      Using the MPHA method with extracted granulocyte and platelet antigens, a
      randomized, blinded trial was conducted to investigate three types of
      alloantibodies in 431 Japanese patients receiving leukocyte-depleted blood
      transfusions prepared with or without our latest leukocyte-reduction filter. The
      frequency of granulocyte, platelet and HLA class I alloantibodies was 0.44%,
      0.44% and 16.74%, respectively, in patients receiving non-filtered products and
      0%, 0% and 0.49%, respectively, in patients receiving filtered products. The
      granulocyte antibody reacted with an antigen approximately of 51 KDa. The
      platelet-specific alloantibody was associated with GPIIb/IIIa and GPIa/IIa. The
      important factors affecting alloimmunization were the transfusion dose and the
      use of unfiltered platelet products.

PMID- 11846131
TI  - Blood component safety.

PMID- 11846132
TI  - Enhanced arm cleansing, diversion of the first aliquot of donation, NAT and their
      impact on blood safety.

PMID- 11846133
TI  - The effects of leucocyte depletion on the generation and removal of microvesicles
      and prion related protein in blood components.

PMID- 11846134
TI  - Helinx technology for inactivation of infectious pathogens and leukocytes in
      labile blood components: from theory to clinical application.

PMID- 11846135
TI  - Methylene blue and thionine in pathogen inactivation of plasma and platelet
      concentrates.

PMID- 11846136
TI  - Current strategies for the provision of safer plasma and its derivatives: an
      update.

PMID- 11846137
TI  - Use of riboflavin for photoinactivation of pathogens in blood components.

PMID- 11846138
TI  - Pathogen inactivation of red cell concentrates using Inactine chemistry.
AB  - The INACTINE process is a promising approach for improving the pathogen safety of
      red cell concentrates. Clinical trials are ongoing to characterize the viability
      of the pathogen inactivated red cells in humans. The presentation will update the
      audience on the preclinical and clinical trials conducted to date.

PMID- 11846139
TI  - Frozen and washed red blood cells: new approaches and applications.

PMID- 11846140
TI  - Current strategies on pathogen removal/inactivation: an overview.

PMID- 11846141
TI  - Up-date on blood component safety: current position of the national blood service
      in England.

PMID- 11846142
TI  - Where are we in France?

PMID- 11846143
TI  - Global views on leukodepletion, bacterial testing, viral removal/inactivation:
      Germany.

PMID- 11846144
TI  - Universal leukoreduction in Iceland validation, process control and quality
      control. Implications for smaller bloodbanks.

PMID- 11846145
TI  - Strategies for improving the safety of blood collection and transfusion: the
      Genoa experience.

PMID- 11846146
TI  - Universal leukoreduction in The Netherlands.

PMID- 11846147
TI  - Transfusion medicine in Norway 2001. Time for change.

PMID- 11846148
TI  - Leucodepletion, bacterial contamination and viral inactivation: a Portuguese
      blood centre experience.

PMID- 11846149
TI  - Leucodepletion, bacterial testing and pathogen removal update and position for
      Scotland: April 2001.

PMID- 11846150
TI  - Leucodepletion (LD) trends and preferred approaches.

PMID- 11846152
TI  - Prioritizing the options for enhancing blood component safety.

PMID- 11846151
TI  - Continuous improvements in national leucodepletion outcome and potential cause of
      leucodepletion failure.

PMID- 11846153
TI  - What's happening? The quality of methylene blue treated FFP and cryo.
AB  - It is currently unclear to what degree methylene blue in combination with
      removal, of cells from plasma, by filter, can directly influence the loss of
      active components of plasma and whether the co-precipitation of FVIII/vWf with
      fibrinogen/fibronectin is affected by combined methylene blue and light treatment
      (MBLT). These questions are investigated using the Fenwal system. Our results
      indicate that up to 15% of the FVIII and IX are lost due to exposure of plasma to
      filters and methylene blue (MB). The illumination leads to a further 10-15% loss
      of all other major clotting factors. Factor XI appears to be highly sensitive to
      the MBLT-process, while inhibitors of the coagulation system are less affected.
      MBLT did not grossly influence the distribution of fVIII/vWf:Ag between
      cryoprecipitate and cryosupernatant using a paired control/test protocol,
      although the fVIII/vWf recovery is reduced in MBLT samples. The three
      commercially available MBLT processes differ in terms of operational aspects.
      These may have some impact on overall quality/safety and bioequivalency.

PMID- 11846154
TI  - Antibody Magnitude Score: a new concept combining the extent and the strength of
      alloantibody.

PMID- 11846155
TI  - Multi-dimensional evaluation and ranking of coastal areas using GIS and multiple
      criteria choice methods.
AB  - Coastal ecosystems are increasingly threatened by short-sighted management
      policies that focus on human activities rather than the systems that sustain
      them. The early assessment of the impacts of human activities on the quality of
      the environment in coastal areas is important for decision-making, particularly
      in cases of environment/development conflicts, such as environmental degradation
      and saturation in tourist areas. In the present study, a methodology was
      developed for the multi-dimensional evaluation and ranking of coastal areas using
      a set of criteria and based on the combination of multiple criteria choice
      methods and Geographical Information Systems (GIS). The northeastern part of the
      island of Rhodes in the Aegean Sea, Greece was the case study area. A distinction
      in sub-areas was performed and they were ranked according to socio-economic and
      environmental parameters. The robustness of the proposed methodology was assessed
      using different configurations of the initial criteria and reapplication of the
      process. The advantages and disadvantages, as well as the usefulness of this
      methodology for comparing the status of coastal areas and evaluating their
      potential for further development based on various criteria, is further
      discussed.

PMID- 11846156
TI  - Concentrations and leachability of chemical elements in estuarine sulfur-rich
      sediments, W. Finland.
AB  - Concentrations, distributions and mobility of chemical elements were investigated
      in reduced sulfur-rich estuarine sediments located in western Finland. The main
      objective was to determine the possible extent of metal leaching when dredged
      masses of these sulfur-rich sediments are dumped on the land and thus exposed to
      air. When dredged, the reduced sulfur in the sediments oxidises resulting in a
      lowering of pH, which in turn is expected to leach metals. The study area is an
      artificial lake claimed from the Botnian sea in 1962. In this lake, several mass
      kills of fish have occurred, believed partly to be due to dredging. Two sediment
      samples (0-50 and 50-100 cm) were taken from 39 sampling points in the lake.
      These samples were leached in aqua regia (2:2:2 HNO3/HCl/H2O1) and analysed for
      Fe, Al, Mg, Ca, K, P, Na, Mn, Zn, Ba, V, Sr, Cr, Ni, Cu, Co, As, Pb, B, Mo and Cd
      with ICP-AES. Sulfur and organic carbon were analysed with Leco. In a controlled
      laboratory experiment, the sediments were allowed to oxidise for 1 year while
      moisturised with deionised water every month. The pH and conductivity were
      determined in the beginning of the experiment (reduced state) and in the end
      (oxidised state). In the supernatants in the oxidised states the amount of
      leached metals (Na, Al, Mn, Zn, Sr, Co, Ni, Cu, Cd, Cr, Pb, U, Li, Rb and As)
      were determined with ICP-MS. The sediments were found to contain low levels of
      toxic metals but, as expected, high concentrations of sulfur. In the experiment,
      pH was lowered (down to 3.0) and the conductivity increased in all samples due to
      oxidation and release of metal ions. The extent of leaching varied between 0.03%
      for As and 12.3% for Na. Critical pH values, at which high amounts of metals
      begin to leach, were obtained graphically. These values varied between 4.8 (Ni)
      and 3.3 (Cr). Not all elements were controlled by pH, e.g. Mn correlated well
      with its aqua regia leachable concentration. In a planned dredging operation in
      the area some 23,300 t (10,500 m3) (dry wt.) of sediments will be dredged. The
      amounts of metals likely to be leached, according to the results from this study,
      are as follows (kg): Al (1710), Mn (1230), Zn (59), Sr (39), Co (13), Ni (12), Cu
      (2) and less than 1 kg of Cd-Cr-As-Pb.

PMID- 11846157
TI  - Incomplete degradation of linear alkylbenzene sulfonate surfactants in Brazilian
      surface waters and pursuit of their polar metabolites in drinking waters.
AB  - In Brazil more than 90% of the population are not connected to municipal
      wastewater treatment plants. As a consequence, surface waters receive
      continuously considerable amounts of untreated domestic sewage containing
      surfactants as a major constituent. Such polluted waters gave rise to special
      interest if they are used as a source for the production of drinking water. In
      this work, the river Rio Macacu (State Rio de Janeiro, Brazil) was monitored for
      the occurrence of the most widely used anionic surfactant linear alkylbenzene
      sulfonate (LAS) together with its main degradative product, sulfophenyl
      carboxylates (SPC). In order to pursue the fate of both compounds after emission
      into the river, samples were collected at several locations along the river bank,
      and analyzed applying liquid chromatography-mass spectrometry after enrichment by
      solid-phase extraction. The LAS concentrations ranged between 14 and 155 microg
      l(-1) and the levels of their metabolic intermediates were found from 1.2 to 14
      microg l(-1). The self-purification capacity of the water was impressively
      demonstrated in the upper course of the river downstream of a town considered as
      one major discharge point, whereas in the lower course the relative constant
      concentrations of both analytes were detected which was explained with an overall
      increasing level of pollution. Furthermore, a series of drinking water samples
      from Niteroi and Sao Goncalo, supplied by the same waterworks treating surface
      waters from the Rio Macacu, were taken during two sampling periods and examined
      for the presence of the strongly polar SPC which is suspected of by-passing the
      purification processes. The levels detected in the drinking water ranged between
      1.6 and 3.3 microg l(-1). For the analyses of drinking and surface waters the
      peak pattern of a selected SPC homologue composed by several positional isomers
      served as an indicator to describe the progression of SPC degradation occurred in
      the river and could be used to distinguish drinking waters of different origins.

PMID- 11846158
TI  - Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on trace elements, inflammation and
      viral clearance in the myocardium during coxsackievirus B3 infection in mice.
AB  - A myocarditic coxsackievirus B3 (CB3) infection in adult male A/J mice was used
      to investigate the effects of 2,3,7,8-tetrachlorodibenzo-para-dioxin (TCDD)
      exposure on mortality and on inflammatory lesion, virus and trace element
      contents of the heart. The mice were injected with four weekly intraperitoneal
      (i.p.) injections of TCDD (a loading dose of 5 microg/kg followed by three
      maintenance doses of 1.4 microg/kg). To reach a steady-state body burden of TCDD
      the mice were allowed a 90-day recovery period before infection with CB3 virus.
      TCDD increased the infection-induced mortality rate, whereas in TCDD-exposed
      mice, heart lesions at day 7 after the virus inoculation (median value 0.67% of
      the tissue section area; interquartile range 0.28; not statistically significant)
      were one-third of that in non-exposed infected mice (2.07% of the tissue section
      area; interquartile range 3.06). The size of the inflammatory heart lesion
      correlated to the amount of virus (r(s) = 0.829, P < 0.01) as well as to the
      calcium (Ca: r(s) = 0.725, P < 0.01) and the magnesium (Mg: r(s) = -0.615, P <
      0.05) contents. In TCDD-exposed mice in situ hybridisation of viral RNA in the
      myocardium at day 7 showed a tendency to decreased amounts of virus, as well as a
      less pronounced increase in myocardial Ca content, both supporting a milder
      myocardial disease after TCDD exposure. No effect of TCDD exposure was seen on
      the zinc (Zn) or selenium (Se) levels in the myocardium. In conclusion, although
      TCDD seemed to have a limiting effect on viral replication and the development of
      the inflammatory lesion in the myocardium, mortality was increased by TCDD in
      this infection model. However, TCDD had no significant effects on the selected
      trace elements that could be of importance for the severity of the inflammatory
      lesion (Ca, Se), for the local host response activation (Zn) or for the
      development of myocardial disease complications (Mg). Accordingly, the increased
      mortality may be a result of an infection-induced increase in TCDD toxicity to
      vital organs other than the heart, and/or a TCDD-induced change in the tissue
      affinity and virulence of the virus, possibly causing involvement of other target
      organs in the infectious process and changed pathogenesis.

PMID- 11846159
TI  - Nitrate reductase activity in some subarctic species and UV influence in the
      foliage of Betula pendula Roth. seedlings.
AB  - Nitrate reductase (NR) activity was studied in the foliage of five subarctic
      species: mature trees of European white birch (Betula pubescens Erch. S.S.),
      Scots pine (Pinus sylvestris L.), Norway spruce (Picea abies L. Karst),
      Ericaceous shrub bilberry (Vaccinium myrtillus L.), naturally growing in a
      forest, and seed-grown silver birch (Betula pendula Roth.) seedlings in an
      ultraviolet (UV) exclusion field experiment at the Pallas-Ounastunturi National
      Park in Finnish Lapland (68 degrees N). Mean NR activity ranged from 0 in
      bilberry to 1477 (S.D. = 277.7) and 1910 (S.D. = 785.4) nmol g(-1) DW h(-1) in
      mature trees of European white birch and silver birch seedlings, respectively.
      Significant differences due to UV exclosure treatments were determined for the NR
      activity of silver birch seedlings (F = 3.62, P= 0.025*) after three growing
      seasons (191 days) of UV exclusion. The ambient and control silver birch
      seedlings had or tended to have higher NR activity than those grown under UV
      exclusion. No relationship was found between the foliage NR activity and total
      nitrogen content, which ranged from 0.61 to 1.35% per seedling. The present study
      suggests large differences in NR activity between the species and the induction
      of NR activity in silver birch seedlings due to ambient UV radiation.

PMID- 11846160
TI  - Weather system scale variation in radon-222 concentration of indoor air.
AB  - Radon-222 concentration measurements using the charcoal adsorption technique were
      made continuously over periods of up to 2 years in three houses, two rural and
      one urban. The measurement records for all houses show a variation in radon
      concentration on a seasonal scale on which is superimposed shorter periods of
      relatively large magnitude fluctuations on a scale longer than the typically 4-5
      day measurement duration. Regression analysis using meteorological data from a
      weather station remote from the houses shows that much of the variation in both
      monthly and 3-day mean radon concentration can be explained by regional scale
      external temperature variation. Wind speed, rainfall and barometric pressure
      apparently influence the 3-day values to a much smaller degree. Differences in
      the radon levels between the houses reflect the different geological radon
      potential of the two areas, with notably higher levels over limestone than
      glacial till and sandstone. Other differences within and between houses reflect
      house construction and occupancy factors.

PMID- 11846161
TI  - About the assumption of linearity in soil-to-plant transfer factors for uranium
      and thorium isotopes and 226Ra.
AB  - The linearity assumption for soil and plant concentrations of radionuclides is
      usually a good approximation for use in food-chain models. To verify this
      assumption, different samples of plant and substrate were collected from a
      granitic zone located near a disused uranium mine in order to cover a large range
      of concentrations. In all of the samples, the activity concentration of 226Ra and
      of different isotopes of uranium (238U and 234U) and thorium (232Th, 230Th and
      228Th) were determined. The results indicate that the linearity assumption can be
      considered valid when the range of concentrations taken into account is large
      (approx. two orders of magnitude). Otherwise, there is a clear deviation from
      linearity. Also, the influence of different stable elements on the soil-plant
      transfer factors was studied by using multivariate regression methods. The uptake
      of uranium, thorium and radium was found to be mainly associated with the
      concentration of iron in the plant and the phosphorus and alkaline earths in the
      substrate.

PMID- 11846162
TI  - Estimating distribution and retention of mercury in three different soils
      contaminated by emissions from chlor-alkali plants: part I.
AB  - Mercury emissions from chlor-alkali plants have been past and present sources of
      soil contamination with Hg. Here we calculate net mercury (Hg) deposition to
      soils in the vicinity (100-1000-m downwind) of three-chlor alkali plants.
      Calculations were based on spatial distribution patterns of Hg concentrations in
      soils, which were extrapolated by kriging. Moreover, we investigated to what
      extent Hg deposition depends on the elevation of receptors and canopy
      throughfall. Mercury concentrations in soil exceed background values up to a
      factor of 56 and show enrichment factors between 2 and 5.8 calculated from the
      median Hg concentration. Net deposition rates range between 2356 and 8952 microg
      m(-2) year(-1), which is up to 224-fold the background values. Net deposition of
      Hg to soils at the three sites varies between 1.2 and 2.4% of total emitted Hg.
      Highest deposition rates were found at sites with extended elevated or forested
      areas. Here, Hg concentrations in soils increased by a factor of up to 7.3 in
      elevated (+180 m) forest areas compared to non-elevated grassland soils.

PMID- 11846163
TI  - Release of mercury from dental amalgam and its influence on salivary antioxidant
      activity.
AB  - Dental amalgam fillings are known to release significant amounts of mercury (Hg)
      in saliva which could represent a continuous source of oxidative damage to mouth
      tissues. The present investigation was aimed at verifying this hypothesis by
      determining a possible correlation between salivary Hg levels and salivary total
      antioxidant activity (TAA), which is used as an index of oxidative stress.
      Samples of saliva from 34 healthy donors were analyzed for Hg content, by vapor
      atomic absorption spectrometry, and for TAA, by determining the ferric reducing
      ability ('FRAP' method). A significant correlation between Hg and the number of
      amalgam restorations or total amalgam surface was evident in both the male and
      female subjects. A significant negative correlation between TAA and Hg levels or
      number of amalgam restorations or amalgam surface was evident in females,
      indicating that small increases in salivary Hg were sufficient to produce a
      decrease in salivary TAA. On the other hand, no significant correlation was found
      in the males. The present study provides, for the first time, evidence of a pro
      oxidant role of the amalgam Hg chronically released in saliva.

PMID- 11846164
TI  - Binding and mobility of mercury in soils contaminated by emissions from chlor
      alkali plants.
AB  - Chlor-alkali plants are known to be an important source of Hg emissions to the
      atmosphere and related contamination of soils in their vicinity. In the present
      study, the results of Hg speciation and mobility of Hg in soils affected by Hg
      emissions from three chlor-alkali plants are compared. Solid phase mercury
      speciation analyses was carried out using a mercury-thermo-desorption technique
      with the aim of distinguishing elemental Hg [Hg(0)] from Hg(II)-binding forms.
      Mercury species in soil leachates were distinguished using an operationally
      defined method, which is based on the reactivity of soluble Hg compounds. Results
      show that the Hg(0) emitted from the plants could not be detected in any of the
      investigated soils. This indicates quantitative re-emission or oxidation of this
      Hg species in the atmosphere or soils. In most soils Hg was predominately bound
      to organic matter. Only in sandy soils deficient in organic matter was Hg, to a
      larger extent, sorbed onto mineral soil components. Leachable Hg in most soils
      occurred as non-reactive, soluble organic Hg complexes such as fulvic acid-bound
      Hg, and reach their highest values (90 microg kg(-1)) in soils rich in organic
      matter. Concentrations of reactive, soluble Hg compounds were highest in sandy
      soils where the content of organic matter was low. Leachability of Hg was found
      to be inhibited in soils with a high content of clayey soil components. The
      distribution of Hg in soil profiles suggests that migration of Hg to deeper soil
      layers (approx. 20 cm) is most effective if Hg is bound to soluble organic
      complexes, whereas reactive Hg or weak Hg complexes are effectively retained in
      the uppermost soil layer (5 cm) through sorption on mineral surfaces.

PMID- 11846165
TI  - Spatial distribution and temporal variation of metals in the vicinity of a
      municipal solid waste incinerator after a modernization of the flue gas cleaning
      systems of the facility.
AB  - In June 1994 and 1997, the concentrations of a number of elements were determined
      in soil and herbage samples collected in the vicinity of a municipal solid waste
      incinerator (MSWI) (Tarragona, Catalonia, Spain). In August 1997, an adaptation
      to the EU legislation on pollutant emissions from the stack was carried out to
      the incinerator. In June 1999, soil and herbage samples were collected again at
      the same sampling points and the levels of arsenic (As), cadmium (Cd), chromium
      (Cr), lead (Pb), manganese (Mn), mercury (Hg), nickel (Ni) and vanadium (V) were
      measured by ICP-MS or AAS with graphite furnace. The results are compared with
      those obtained in the 1994 and 1997 surveys. In the period 1997-1999, the only
      significant changes in soil levels corresponded to Cd and Pb, with decreases of
      21.0% and 53.5%, respectively. In vegetation, only Mn levels showed a significant
      reduction, which contrasts with the notable increases found in the concentrations
      of As, Hg and Ni. According to the results of this survey, it seems evident that
      other metal emission sources in the same area of study are masking the
      environmental improvements carried out in the MSWI.

PMID- 11846166
TI  - Waste ashes for use in agricultural production: I. Liming effect, contents of
      plant nutrients and chemical characteristics of some metals.
AB  - The chemical characteristics of 89 municipal waste ashes, including food scrap
      ash (FSA), animal waste ash (AWA), horticulture waste ash (HWA), sewage sludge
      ash (SSA) and incinerator bottom ash (IBA), from various locations in Japan were
      examined with the aim of evaluating their suitability for use in agriculture.
      Although the waste ashes came from different sources and consisted of various
      materials, the gross elemental composition was similar. Acid neutralization
      capacity (liming effect) for the waste ashes was equivalent to 10-30% of CaO and
      followed the sequence SSA > IBA > AWA > FSA > HWA. Average P concentrations for
      the five types of waste ashes ranged from 10 to 29 g kg(-1) and average K
      concentrations ranged from 14 to 63 g kg(-1), respectively. Metal contents in the
      waste ashes were compared with levels in Japanese agricultural soils. K in the
      waste ashes was 1.3-6 times higher and Ca was 3-12 times higher; contents of the
      other metals in FSA, AWA and HWA were generally less than five times higher, but
      Ni, Cu, Zn, Cd, Sn, Pb in SSA or IBA were approximately 10-200 times higher than
      those in soils. Moreover, the ceiling amounts of waste ashes that may be applied
      to main Japanese agricultural soils were calculated by using soil contamination
      standards for Cu. Water solubility of P and metals in the waste ashes were also
      examined.

PMID- 11846167
TI  - Selenium in soil and endemic diseases in China.
AB  - Selenium is an essential element for humans, animals and some species of
      microorganisms. The biological function of selenium shows dual characteristics.
      The selenium content range between toxic and deficient concentration is very
      narrow. The present paper discusses the geographical distribution of two forms
      (total and water-soluble) of selenium in topsoil (plough layer for cultivated
      soils, eluvial horizon for natural soils) and evaluates its relationship with
      some human health problems in China. Topsoil samples, 354 in total, including 156
      natural and 198 cultivated soils of 21 main soil types were collected. The total
      Se concentration in soil samples was determined with DAN (di-aminonaphthalene)
      fluorescence spectrophotometer method. Soil water-soluble Se concentration was
      determined with the same method after extraction with water (water/soil = 5:1).
      The results showed that the geometric and arithmetic means of total Se
      concentration in soil, for all samples, were 0.173 mg/kg and 0.239 mg/kg,
      respectively, with the lowest value being 0.022 mg/kg and the highest being 3.806
      mg/kg. For the cultivated soil, the geometric mean of total Se was 0.188 mg/kg,
      its arithmetic mean was 0.269 mg/kg and higher than those in the natural soil,
      0.154 mg/kg and 0.206 mg/kg, respectively. The geometric and arithmetic means of
      water-soluble Se in soil for all the samples were 4.0 and 6.4 microg/kg, the
      lowest 0.6 microg/kg and the highest value being 109.4 microg/kg. For the
      cultivated soils, the average concentration of water-soluble Se was 4.3
      microg/kg, similar to that of natural soil, they are and 4.4 microg/kg by
      geometric mean. Two sequences of the soil types, arranged separately in the
      concentration of total Se and water-soluble Se, are different and this
      demonstrates that the proportions of the two forms of selenium existing in
      various soils are different. The percentages of water-soluble Se to total Se in
      different types of soils varied from 1.07 to 6.69%. However, generally the
      laterite and other subtropic soil still have relatively high absolute water
      soluble Se contents because of their higher total Se contents. A very significant
      correlation between total Se and water-soluble Se has been found in cultivated
      soil with a correlation coefficient of 0.58 (P < 0.01). The relationships between
      soil Se and human endemic diseases Keshan disease, Kashin-Back diseases and
      selenosis have been discussed. The reference criteria for evaluating Se
      deficiency and Se excess in soil were suggested.

PMID- 11846168
TI  - Partition coefficients for the trihalomethanes among blood, urine, water, milk
      and air.
AB  - Chloroform, bromodichloromethane, chlorodibromomethane, and bromoform comprise
      the trihalomethanes, a group of widespread and mildly lipophilic compounds that
      result from water chlorination and other sources. Many animal studies show the
      chronic toxicity and carcinogenicity of these compounds, and recent work has
      demonstrated the importance of both ingestion and inhalation exposure pathways.
      This study presents partition coefficients describing the equilibrium among
      biological compartments (air, water, blood, milk, urine) for the four THMs based
      on results of headspace gas chromatographic analyses performed under equilibrium
      conditions and at 37 degrees C. The calculated partition coefficients ranged from
      2.92 to 4.14 for blood/water, 1.54-2.85 for milk/blood, and 3.41-4.93 for
      blood/urine, with the lowest being chloroform and the highest being bromoform.
      Both human and cow milk were tested, with similar results. The available samples
      of human milk may not fully account for differences in lipid content and possibly
      other factors that affect estimates of partition coefficients. Simultaneous
      measurements of milk and blood in exposed individuals are suggested to confirm
      laboratory results. Partition coefficients are predicted using the octanol-air
      partition coefficient, also measured in this study, and the octanol-water
      partition coefficient. Results are similar to literature estimates for liquid/air
      partitioning of chloroform and chlorodibromomethane, but they differ from
      predictions based on hydrophobicity and lipid content. High correlations between
      the derived partitioned coefficients and the molecular structure (number of Br
      atoms) and physical properties (molecular weight and boiling point) are found for
      these analogous chemicals. In humans, THMs are both stored and metabolized with
      relatively rapid clearance rates. The derived partition coefficients can help to
      interpret results of biological monitoring and predict the potential for the
      accumulation and transfer of chemicals, specifically by the application of
      physiologically-based pharmacokinetic models. THM exposures to potentially
      susceptible populations, e.g. nursing infants, can be predicted using either such
      models.

PMID- 11846169
TI  - Fish tissue quality in near-coastal areas of the Gulf of Mexico receiving point
      source discharges.
AB  - The objective of this study was to determine inorganic and organic contaminant
      concentrations in edible tissue of fish collected from eight coastal areas
      receiving wastewater discharges and from two reference locations. Trace metal
      residues were statistically similar regardless of the collection site. Zinc (100%
      detection in all samples), total mercury (100%), total arsenic (92%), copper
      (92%), and selenium (88%) were the more commonly detected trace metals. Mercury
      concentrations exceeded the Florida health-based standard of 0.5 microg/g for
      limited fish consumption in 30% of the total samples and averaged 0.40 (+/- 1
      S.D. = 0.22, range < or = 0.08 to 0.85) microg/g wet weight. The average total
      PAH concentrations were 1.79 (+/- 1.60) ng/g (reference areas) and 2.17 (+/-
      3.29) ng/g (wastewater-impacted areas). Pyrene was detected most frequently (63%
      of the total samples) and averaged 0.74 (+/- 0.35) ng/g wet wt. The average total
      PCB concentrations were 4.8 (+/- 7.1) ng/g (reference areas) and 31.6 (+/- 31.3)
      ng/g (wastewater-impacted areas) Concentrations of dieldrin and cis-chlordane
      were approximately eight times greater, respectively, in fish collected from
      wastewater receiving waters, whereas total DDT and total pesticide concentrations
      were not elevated in the same areas. Concentrations of total PCBs and all
      chlorinated pesticides were below US health-based standards. The lack of a
      published reference data base for fish tissue quality in near-coastal areas of
      the Gulf of Mexico restricts an assessment of the environmental significance of
      results from this and similar studies investigating the fate of point source
      contaminants.

PMID- 11846170
TI  - Effect of environmental contaminants on nasal lysozyme secretions.
AB  - Human nasal secretions are comprised of lysozyme and albumin as their main
      protein components. Lysozyme, an anti-microbial substance, is produced by nasal
      serous cells while albumin is obtained, primarily, from increased nasal
      vasculature permeability. We measured lysozyme levels in nasal secretions
      following challenge by a variety of non-infectious environmental contaminants.
      The methodology given presents a simple and rapid method of collecting nasal
      secretions and determining their lysozyme content, a technique which can be used
      for a host of environmental irritants.

PMID- 11846171
TI  - Calculating the new global nuclear terrorism threat.

PMID- 11846172
TI  - Arsenic species in an arsenic hyperaccumulating fern, Pityrogramma calomelanos: a
      potential phytoremediator of arsenic-contaminated soils.
AB  - The fern Pityrogramma calomelanos is a hyperaccumulator of arsenic that grows
      readily on arsenic-contaminated soils in the Ron Phibun district of southern
      Thailand. P. calomelanos accumulates arsenic mostly in the fronds (up to 8350
      microg As g(-1) dry mass) while the rhizoids contain the lowest concentrations of
      arsenic (88-310 microg As g(-1) dry mass). The arsenic species in aqueous
      extracts of the fern and soil were determined by high performance liquid
      chromatography coupled to an inductively coupled plasma mass spectrometer (HPLC
      ICPMS) which served as an arsenic specific detector. Only a small part of the
      arsenic (6.1-12%) in soil was extracted into water, and most of this arsenic (>
      97%) was present as arsenate. The arsenic in the fern rhizoids was approximately
      60% water-extractable, 95% of which was present as arsenate. In contrast, arsenic
      in the fern fronds was readily extracted into water (86-93%) and was present
      mainly as arsenite (60-72%) with the remainder being arsenate. Methylarsonate and
      dimethylarsinate were detected as trace constituents in only two fern samples.
      Preliminary estimates of phytoremediation potential suggest that P. calomelanos
      might remove approximately 2% of the soil arsenic load per year. With due
      consideration to the type of arsenic compounds present in the fern, and their
      water-solubility, the option of disposing high arsenic ferns at sea is raised for
      discussion.

PMID- 11846173
TI  - Effects of coxsackievirus B3 infection on the acute-phase protein metallothionein
      and on cytochrome P-4501A1 involved in the detoxification processes of TCDD in
      the mouse.
AB  - During acute infections, the synthesis of acute-phase proteins and other proteins
      participating in the host defence are stimulated in the liver and kidney. In
      previous studies of coxsackievirus B3 (CB3) infection in mice, we found that
      cadmium (Cd) accumulates in the kidney, whereas 2,3,7,8-tetrachlorodibenzo-p
      dioxin (TCDD) accumulates in the liver. To study if CB3 infection affects the
      synthesis of the Cd-binding protein metallothionein (MT) and the TCDD
      binding/detoxifying cytochrome P-450 (CYP-450) isozyme CYP1A1, the basal and TCDD
      induced levels of serum MT and liver CYP1A1 isozyme were determined in healthy
      and CB3-infected A/J mice. Furthermore, because interferons affect CYP450
      activity, the serum levels of the interferons alpha (IFN-alpha) and -beta (IFN
      beta) were measured in CB3-infected mice and in mice treated with the interferon
      inducer polyinosinic/polycytidylic acid (poly I/C). Virus or poly I/C was
      administered intraperitoneally (i.p.) on day 0 and 500 ng TCDD/kg bodyweight on
      day 1. On day 4, CB3 infection had induced MT approximately 10-fold, regardless
      of TCDD treatment (P < 0.01 in infected mice and P < 0.001 in infected, TCDD
      treated mice). TCDD alone induced a 10-fold increase in CYP1A1 activity (P <
      0.001), whereas infection alone suppressed the normal CYP1A1 activity by 75% (P <
      0.001). Infection also suppressed the TCDD-induced CYP1A1 activity by
      approximately 30% (n.s.). Poly I/C suppressed CYP1A1 by 20-25% (n.s.) at both
      basal and TCDD-induced levels. Serum IFN-alpha and IFN-beta levels were
      undetectable in controls, in TCDD-treated and in the poly I/C-treated groups on
      day 4, probably because the short IFN peak is detectable only hours after
      injection. Conversely, on day 4 of the infection, IFN-alpha and IFN-beta were
      consistently raised in the TCDD-treated infected mice, whereas increased IFNs as
      a result of infection alone could be detected in only one individual. These
      results suggest that the normal host responses during acute infections down
      regulate detoxifying processes in favour of acute-phase protein synthesis. This
      may explain the observed changed pattern of accumulation, excretion and toxicity
      of the environmental pollutants cadmium and TCDD during this common virus
      infection.

PMID- 11846174
TI  - Statistical study of the relationship between free chlorine levels and
      bacteriological checks on systems in the Paris area.
AB  - The majority of French cities are supplied with treated surface water. The
      primary factor in determining the quality of this water concerns disinfection to
      ensure that the system is not contaminated with parasites, coliforms and
      streptococci; some of these organisms, especially coliforms, are capable of
      multiplying within the system. The presence of bacteria indicative of faecal
      contamination in water samples, which contains a significant amount of free
      chlorine, has revealed a possible link between the two. Based upon sampling
      points of the Parisian system (and in the suburbs for purposes of comparison), we
      show the existence of a linear relationship between the results of analyses for
      coliforms on a given day, D, and the content of free chlorine in the water on
      days D-2 and D-3. Subsequent ground tests confirm the explanations proposed
      regarding these phenomena.

PMID- 11846175
TI  - Assessing the influence of methanol-containing additive on biological
      characteristics of diesel exhaust emissions using microtox and mutatox assays.
AB  - Here we investigate the effect of the methanol-containing additive (MCA) on the
      biological characteristics of diesel exhaust emissions. Microtox and Mutatox
      assays, respectively, were used to evaluate the acute toxicity and genotoxicity
      of crude extracts from diesel engine exhaust. The engine was tested on a series
      of diesel fuels blended with five additive levels (0, 5, 8, 10 and 15% of MCA by
      volume). Emission tests were performed over the hot start portion of the
      transient Heavy-Duty-Federal Test Procedure (HD-FTP) and two selected steady
      state modes. Microtox results show that MCA additive moderately lowers the
      toxicity levels of particle-associated (SOF) samples, but generally increase the
      vapor-phase (XOC) associated toxicity. A strong correlation was found between XOC
      associated toxicity and total hydrocarbon (THC) concentrations, while only a
      slight link was found between SOF-associated toxicity and particulate matter (PM)
      concentrations. For Mutatox test results, when either 5 or 8% MCA used, XOC and
      SOF-associated genotoxicity in both steady-state and hot-start transient cycle
      tests were relatively lower compared to those of the base diesel. The genotoxic
      potential of XOC samples was significantly increased after treatment with an
      exogenous metabolic activation system (S9). On the contrary, the genotoxic
      potential of SOF samples without S9 metabolic activation was generally higher
      than those with S9. It is noteworthy that the total particle-associated (SOF)
      PAHs emissions showed trends quite similar to that of the genotoxic potential. As
      expected, the total particle-associated (SOF) PAHs correlated moderately with
      direct mutagenicity, and fairly well with indirect mutagenicity. Finally, the
      genotoxicity data did not parallel the Microtox results in this study, indicating
      that potentially long-term genotoxic agents may not be revealed by short-term
      toxicity assays.

PMID- 11846176
TI  - Association between chronic exposure to pesticides and recorded cases of human
      malignancy in Gaza Governorates (1990-1999).
AB  - Epidemiological association between chronic exposure to pesticides and recorded
      cases of human malignancy in Gaza Governorates during the years 1990-1999 was
      studied. The pesticide usage in Gaza Governorates was recorded in detail. It
      ranged from 216.9 to 393.3 t from 1990 to 1999, respectively. Banned and
      extremely hazardous pesticides are identified according to their carcinogenicity,
      genotoxicity and cytotoxicity. Hospital cases of cancers in men and women were
      recorded. Each tumor type was grouped according to sex and age group from 0 to >
      65 years. Total cases recorded in males were 2277, with average annual incidence
      and age-adjusted rate/100,000 was 53.2 and 96.8 respectively, whereas the total
      for females was 2458 cases, average annual incidence and age-adjusted
      rate/100,000 was 59.7 and 105.3, respectively, over the same 10 years. Lung
      cancer, lymphomas, leukemia, cancers of the urinary bladder, prostate, brain,
      colon, stomach and liver were the most abundant among males, while breast cancer,
      leukemia, lymphomas, cancers of the brain, uterus, lung, thyroid gland and liver
      were the most abundant in females. Statistical analysis using correlation
      coefficients and P values showed highly significant positive correlations between
      the type of pesticide and cancer incidence for male, female and both sexes.
      Correlation coefficients and P values, respectively, for both sexes were: 0.992
      and 0.000 for insecticides; 0.952 and 0.000 for fungicides; 0.812 and 0.004 for
      herbicides; 0.925 and 0.000 for nematicides; 0.992 and 0.000 for others; and
      0.994 and 0.000 for all types of pesticides. In the densely populated
      agricultural areas, it is not possible to separate or differentiate between
      occupational and general public exposure. Consequently, the introduction of and
      heavy use and misuse of pesticides and other toxic substances in the Gaza
      environment is suspected to correlate with the growing incidence of cancer.
      Precise determination of the effects of chronic exposure is, therefore, urgently
      needed. Future legislation to stop and regulate the use of extremely hazardous
      compounds will be essential. Continuous records for chronic diseases and cancers
      are also required for future follow-ups and periodical risk-assessment
      evaluations. Hence, further epidemiological studies are needed with detailed
      exposure assessment for individual pesticides, taking measures to reduce risk
      into consideration.

PMID- 11846177
TI  - Using structural equation model to explore occupational lead exposure pathways.
AB  - The aim of the present study was to demonstrate the use of a structural equation
      model to explore the complicated lead exposure pathways in a lead battery plant.
      A total of 96 out of 113 assembly workers were recruited in this study. Lead
      measurements included blood lead, respirable airborne lead, and body surface lead
      loadings. Latent variables of inadvertent contact of lead on fingers and ingested
      lead had indirect and direct effects on the blood lead levels, respectively, and
      so did the variables of respirable airborne lead, smoking, and the working-place
      clothes being washed. A model chi(22)2 value of 31.1 (P=0.094) for a goodness of
      fit test indicates that the derived structural equation model appropriately
      accounted for the variation of blood lead levels. It is concluded that lead
      loadings on fingers and lips had significant effects on occupational lead uptake,
      and, after-work hours and break times at work were the critical time periods for
      inadvertent lead exposure.

PMID- 11846178
TI  - An analysis of control reversal errors during unusual attitude recoveries using
      helmet-mounted display symbology.
AB  - BACKGROUND: Spatial disorientation (SD) refers to pilots' inability to accurately
      interpret the attitude of their aircraft with respect to Earth. Unfortunately, SD
      statistics have held constant for the past few decades, through the transition
      from the head-down attitude indicator (Al) to the head-up display (HUD) as the
      attitude instrument. The newest attitude-indicating device to find its way into
      military cockpits is the helmet-mounted display (HMD). HMDs were initially
      introduced into the cockpit to enhance target location and weapon-pointing, but
      there is currently an effort to make HMDs attitude reference displays so pilots
      need not go head-down to obtain attitude information. However, unintuitive
      information or inappropriate implementation of on-boresight attitude symbology on
      the HMD may contribute to the SD problem. OBJECTIVE: The occurrence of control
      reversal errors (CREs) during unusual attitude recovery tasks when using an HMD
      to provide attitude information was investigated. The effect of such errors was
      evaluated in terms of altitude changes during recovery and time to recover.
      METHODS: There were 12 pilot-subjects who completed 8 unusual attitude recovery
      tasks. RESULTS: Results showed that CREs did occur, and there was a significant
      negative effect of these errors on absolute altitude change, but not on total
      recovery time. Results failed to show a decrease in the number of CREs occurring
      when using the HMD as compared with data from other studies that used an Al or a
      HUD. CONCLUSIONS: Results suggest that new HMD attitude symbology needs to be
      designed to help reduce CREs and, perhaps, SD incidences.

PMID- 11846179
TI  - Altered cytochrome P450 and P-glycoprotein levels in rats during simulated
      weightlessness.
AB  - BACKGROUND: In order to investigate the effects of simulated weightlessness on
      drug metabolism, liver, kidney, and small intestine, microsomal proteins from
      tail-suspended rats were analyzed to determine cytochrome P450 (CYP) and P
      glycoprotein levels following varying durations of tail-suspension. HYPOTHESIS: P
      glycoprotein and CYP levels would both decrease similar to previous findings from
      actual spaceflight data. METHODS: Six groups of four Sprague-Dawley rats each
      were tail-suspended for up to 21 d; CYP and P-glycoprotein levels in the liver,
      kidney and small intestine were then measured by Western blotting. The results
      were compared with a control group of unsuspended rats. RESULTS: Our data showed
      there were significant changes in the levels of hepatic CYP2C11, 2E1, 4A1, and P
      glycoprotein and significant changes in the levels of P-glycoprotein and CYP4A1
      in the kidney. However, there were no significant changes detected in the levels
      of CYP3A2 in the liver or small intestine. CONCLUSIONS: We conclude that
      simulated weightlessness, using the tail-suspended rat model, showed significant
      suppressive effects on levels of CYP2C11, 2E1, and P-glycoprotein in the liver
      and CYP4A1 in the kidney, while demonstrating no significant effect on the levels
      of CYP3A2 in the liver or small intestine. Thus, generalized predictions on the
      effect of simulated microgravity on drug metabolism cannot be made and the
      overall effect of spaceflight on individual enzymes should be investigated.

PMID- 11846180
TI  - The effects of timing and application of vibration on muscular contractions.
AB  - BACKGROUND: The effect of vibration stimulation on muscular strength is an
      emerging field of research and very little comprehensive work has been conducted
      at this stage. HYPOTHESIS: There will be no effects of timing or application of
      vibration stimulation on muscular strength and activation across isometric,
      isokinetic and concentric isotonic contractions. METHODS: There were 28
      recreational athletes who participated in this study. Their characteristics were:
      (mean +/- SD) age, 22.8 +/- 5.6 yr; height, 174.1 +/- 8.8 cm; and body mass, 78.0
      +/- 13.6 kg. The vibration stimulation was delivered at 50.42 +/- 1.16 Hz with an
      acceleration of 13.24 +/- 0.18 ms(-2). RESULTS: A series of one-way ANOVAs
      revealed significant (p < 0.05) improvements of 14.7 +/- 2.9% and 15.3 +/- 3.1%
      above normal contraction levels for concentric isotonic strength during and after
      the vibration stimulation, respectively. No significant improvements in isometric
      and isokinetic strength were evident. Concurrent measurement of electromyography
      (EMG) presented significant improvements during stimulation of 30.1 +/- 14.6%,
      43.0 +/- 13.0%, and 107.1 +/- 44.4% in mean activation of rectus femoris (RF) for
      the isometric, isokinetic, and concentric isotonic contractions, respectively.
      Synchronous collection of vibromyography (VMG) during stimulation displayed a
      significant decrease of -6.4 +/- 1.5%, -5.1 +/- 1.2%, and -4.1 +/- 1.7% in mean
      VMG activity of RF for the isometric, isokinetic, and concentric isotonic
      contractions, respectively. CONCLUSIONS: Significant improvements in muscular
      strength and activation for concentric isotonic contractions performed during an
      applied vibration suggest that the optimal timing of a vibratory stimulation
      would be while the participant is contracting isotonically. However, further
      research needs to be conducted to establish the exact mechanism behind these
      improvements.

PMID- 11846181
TI  - Non-invasive measurement of pulmonary artery pressure in humans with simulated
      altitude-induced venous gas emboli.
AB  - BACKGROUND: Decompression to simulated altitude causes super-saturation of
      nitrogen desolved in body tissues and can result in venous gas emboli (VGE),
      which are usually "cleared" in the lung. Large intravenous boli of air
      administered to animals increase pulmonary artery pressure (PAP), and may induce
      cross-over of gas to the left side of the heart (creating dangerous arterial gas
      emboli). This study was conducted to determine whether high VGE grades induced at
      simulated altitude elevate PAP in humans. METHODS: Eight human subjects with
      subclinical tricuspid regurgitation were exposed to simulated altitude of > or =
      24,000 ft (7315 m) for up to 4 h. Systolic PAP was derived from Doppler
      ultrasound echo imaging measurements of peak flow velocity of the regurgitant
      jet. VGE was rated using the Spencer scale. A technique of "bubble titration" was
      employed with changes in exercise and altitude to maintain sufficient bubbles
      without decompression sickness. RESULTS: All subjects developed grade III-IV VGE,
      but 3 developed decompression sickness, resulting in earlier termination. Pre
      exposure systolic PAP averaged 24.4 +/- 1.3 (SE) mm Hg. After 1, 2, 3 and 4 h,
      systolic PAP was 23.7 +/- 1.2 (n = 8), 23.4 +/- 1.1 (n = 8), 23.3 +/- 1.0 (n =
      6), and 25.9 +/- 0.6 (n = 5) mm Hg, respectively. Systolic PAP remained
      unchanged, in spite of bubble grades III-IV for up to 4 h. CONCLUSION: As
      systolic PAP did not increase with hypobaric exposures that created substantial
      VGE, the bubble loading was not sufficient to overwhelm the lung clearing
      capacity. The risk of high PAP resulting in VGE cross-over is low during typical
      operational altitude exposures.

PMID- 11846182
TI  - Human factors in aviation crashes involving older pilots.
AB  - BACKGROUND: Pilot errors are recognized as a contributing factor in as many as
      80% of aviation crashes. Experimental studies using flight simulators indicate
      that due to decreased working memory capacity, older pilots are outperformed by
      their younger counterparts in communication tasks and flight summary scores.
      OBJECTIVE: This study examines age-related differences in crash circumstances and
      pilot errors in a sample of pilots who flew commuter aircraft or air taxis and
      who were involved in airplane or helicopter crashes. METHODS: A historical cohort
      of 3306 pilots who in 1987 flew commuter aircraft or air taxis and were 45-54 yr
      of age was constructed using the Federal Aviation Administration's airmen
      information system. Crash records of the study subjects for the years 1983-1997
      were obtained from the National Transportation Safety Board (NTSB) by matching
      name and date of birth. NTSB's investigation reports were reviewed to identify
      pilot errors and other contributing factors. Comparisons of crash circumstances
      and human factors were made between pilots aged 40-49 yr and pilots aged 50-63
      yr. RESULTS: A total of 165 crash records were studied, with 52% of these crashes
      involving pilots aged 50-63 yr. Crash circumstances, such as time and location of
      crash, type and phase of flight, and weather conditions, were similar between the
      two age groups. Pilot error was a contributing factor in 73% of the crashes
      involving younger pilots and in 69% of the crashes involving older pilots (p =
      0.50). Age-related differences in the pattern of pilot errors were statistically
      insignificant. Overall, 23% of pilot errors were attributable to inattentiveness,
      20% to flawed decisions, 18% to mishandled aircraft kinetics, and 18% to
      mishandled wind/runway conditions. CONCLUSIONS: Neither crash circumstances nor
      the prevalence and patterns of pilot errors appear to change significantly as age
      increases from the 40s to the 50s and early 60s.

PMID- 11846183
TI  - Pulmonary barotrauma-induced cerebral arterial gas embolism with spontaneous
      recovery: commentary on the rationale for therapeutic compression.
AB  - Pulmonary barotrauma-induced cerebral arterial gas embolism (CAGE) continues to
      complicate compressed gas diving activities. Inadequate lung ventilation
      secondary to inadvertent breath holding or rapid buoyant ascent can quickly
      generate a critical state of lung over-pressure. Pulmonary over-pressurization
      may also occur as a consequence of acute and chronic pulmonary pathologies.
      Resulting barotrauma frequently causes structural failure within the terminal
      distal airway. Respiratory gases are then free to embolize the systemic
      circulation via the pulmonary vasculature and the left heart. The brain is a
      common target organ. Bubbles that enter the cerebral arteries coalesce to form
      columns of gas as the vascular network narrows. Small amounts of gas frequently
      pass directly through the cerebral circulation without occlusion. Larger columns
      of gas occlude regional brain blood flow, either transiently or permanently,
      producing a stroke-like clinical picture. In cases of spontaneous redistribution,
      a period of apparent recovery is frequently followed by relapse. The etiology of
      relapse appears to be multifactoral, and chiefly the consequence of a failure of
      reperfusion. Prediction of who will relapse is not possible, and any such relapse
      is of ominous prognostic significance. It is advisable, therefore, that CAGE
      patients who undergo spontaneous recovery be promptly recompressed while
      breathing oxygen. Therapeutic compression will serve to antagonize leukocyte
      mediated ischemia-reperfusion injury; limit potential re-embolization of brain
      blood flow, secondary to further leakage from the original pulmonary lesion or
      recirculation of gas from the initial occlusive event; protect against embolic
      injury to other organs; aid in the resolution of component cerebral edema; reduce
      the likelihood of late brain infarction reported in patients who have undergone
      spontaneous clinical recovery; and prophylax against decompression sickness in
      high gas loading dives that precede accelerated ascents and omitted stage
      decompression.

PMID- 11846184
TI  - Development of U.S.-Russian medical support procedures for long-duration
      spaceflight: the NASA-Mir experience.
AB  - As the Russian Space Agency and the U.S. National Aeronautics and Space
      Administration began in the mid-1990s to plan a preliminary cooperative flight
      program in anticipation of the International Space Station, programmatic and
      philosophical differences became apparent in the technical and medical approaches
      of the two agencies. This paper briefly describes some of these differences and
      the process by which the two sides resolved differences in their approaches to
      the medical selection and certification of NASA-Mir crewmembers. These
      negotiations formed the basis for developing policies on other aspects of the
      medical support function for international missions, including crew training,
      preflight and postflight data collection, and rehabilitation protocols. The
      experience gained through this cooperative effort has been invaluable for
      developing medical care capabilities for the International Space Station.

PMID- 11846185
TI  - You're the flight surgeon. Somnambulism (sleepwalking).

PMID- 11846186
TI  - Redefining the approach to aircrew protection: helicopter aircrew integrated life
      support systems.

PMID- 11846187
TI  - Psychological changes and group dynamics during confinement in an isolated
      environment.
AB  - PURPOSE: Cultural and personal traits will become important as the number of
      short-duration spaceflights of international crews supporting the International
      Space Station (ISS) increases and more people begin staying aboard ISS for longer
      durations. This project investigated the interpersonal and personal changes of
      Japanese subjects during a 1-wk stay in the Japanese Experiment Module. The
      Giebetaen Test (GT) was used to determine if the cultural background and
      personality traits of the subjects become more explicit and stronger during
      isolation. METHODS: Six males and two females aged 22-28 yr participated in the
      study. They stayed 7 d in the isolation chamber at the National Space Development
      Agency of Japan (NASDA). The GT was chosen as an individual and group diagnostic
      instrument; it was administrated four times during, and one time after,
      isolation. RESULTS: According to the GT-self-picture, subjects exhibited a change
      toward negative social resonance and social withdrawal. Subgroups formed but
      caused no isolation or tension. The GT-foreign-pictures showed that the judgment
      of other subjects changed toward hedonic and permeability directions. The common
      interpersonal relationships of the Japanese subjects influenced the group
      dynamics. These relationships tend to be integrative and tend to support the
      network and value systems, emphasizing connectedness and minimizing differences.
      CONCLUSION: The cultural background became more explicit and stronger during
      isolation. Based on this, isolation studies with international crews and
      intercultural training will be necessary for international crews performing both
      short- and long-duration missions.

PMID- 11846188
TI  - Safety of air travel following acute myocardial infarction.
AB  - BACKGROUND: A randomized, single-blind, controlled trial was carried out to: 1)
      examine the safety of patients flying on commercial airlines 2 wk after a
      myocardial infarction; 2) determine whether or not the use of supplemental oxygen
      was associated with a reduced risk of in-flight adverse events; and 3) determine
      the need for a medical escort. METHODS: There were 38 patients who were
      prospectively and randomly assigned supplemental continuous oxygen therapy (2 L x
      min(-1) via nasal prongs; n = 19) or no oxygen (n = 19) during the flight. Prior
      to flying, an escorting doctor completed a medical questionnaire for each
      patient. Both groups underwent Holter monitoring throughout the flight. The major
      end-point was the development of inflight myocardial ischemia, as detected by
      Holter monitoring. Minor end-points included patients complaining of chest pain
      or dyspnea; the detection of bigeminy or trigeminy by Holter monitoring; or
      oxygen desaturation to less than 90%, as measured by pulse oximetry. RESULTS: Of
      the 38 patients enrolled, there was only 1 major end-point. This patient had a
      brief, self-limiting, asymptomatic episode of myocardial ischemia diagnosed by
      Holter monitoring. Minor end-points occurred in 13 (34%) patients. One patient
      had asymptomatic evidence of S-T depression on a transport monitor, but not on
      the Holter. Five patients had transient low (<90%) oxygen saturations, two
      complained of chest pain, and five had complex ventricular ectopic beats or
      periods of transient ventricular tachycardia. None of the minor end-points were
      associated with Holter evidence of myocardial ischemia. Of the 30 patients with
      completed questionnaires and Holter results, there was no difference in the
      incidence of minor end-points between the oxygen (5/13) and no oxygen groups
      (6/15) (p = 0.93). Intervention by the medical escort consisted of commencing
      oxygen therapy on those patients with low oxygen saturations and those with chest
      pain. Use of an already dispensed glyceryl trinitrate spray was initiated in one
      patient with chest pain that turned out to be non-ischemic when the Holter traces
      were later analyzed. CONCLUSIONS: This study suggests that, provided that care is
      taken during the immediate preflight and postflight phases not to overexert the
      patients, neither supplemental oxygen nor medical escorts are needed in the
      transportation of patients who fly 2 wk after acute myocardial infarction.

PMID- 11846189
TI  - A word of caution! (Is there a doctor on board?).

PMID- 11846190
TI  - Gingival crevicular fluid matrix metalloproteinase-8 levels following adjunctive
      use of meloxicam and initial phase of periodontal therapy.
AB  - BACKGROUND: The purpose of the present study was to assess the effects of
      adjunctive meloxicam on the matrix metalloproteinase-8 (MMP-8) levels of gingival
      crevicular fluid (GCF) in chronic periodontitis patients following the initial
      phase of periodontal therapy. METHODS: Twelve chronic periodontitis patients
      received 7.5 mg meloxicam, and 10 patients received placebo tablets together with
      scaling and root planing in a 1 x 1 regimen for 10 days. Scaling and root planing
      were performed on day 3 of drug intake. The MMP-8 levels in GCF samples obtained
      before and on day 10 of drug intake were determined by using the
      immunofluorescence assay. Plaque index (PI), papilla bleeding index (PBI), and
      GCF MMP-8 levels were compared within each patient group, between the 2 patient
      groups, and also with a clinically healthy control group using non-parametric
      statistical analyses. RESULTS: Both meloxicam and placebo groups showed
      statistically significant reductions in PBI, PI, and GCF MMP-8 levels on day 10
      compared to baseline (P<0.01). The GCF MMP-8 level on day 10 in the meloxicam
      group was similar to the clinically healthy control group (P>0.05), while it was
      significantly higher in the placebo group (P<0.01). Positive correlations were
      found between MMP-8 total amounts and PBI scores at baseline and day 10 of drug
      intake in the patient groups. CONCLUSIONS: Meloxicam showed a tendency to reduce
      GCF MMP-8 levels in vivo within the first 10 days when used as an adjunct in the
      initial phase of periodontal treatment that consists of scaling and root planing.
      Verification of this effect on collagenase-2 downregulation, as well as on the
      clinical periodontal parameters in long-term studies using larger test and
      control groups, is needed to provide further support for the adjunctive use of
      selective cyclooxygenase (COX)-2 inhibitors in the treatment of chronic
      periodontitis.

PMID- 11846191
TI  - Viral etiology of gingival recession. A case report.
AB  - Herpes simplex virus-type I (HSV-1) is responsible for both primary and recurrent
      infections of the oral mucosa. The aim of this case report is to show how HSV-1
      may cause periodontal damage such as gingival recession. A 26-year-old male
      patient presented in a private office for the treatment of gingival recessions.
      He reported that the recessions had appeared suddenly with marginal inflammation
      of the gingiva and vesicle formation; within a few hours, the gingival tissue had
      been completely destroyed. The lesions were accompanied by pain, fever, and
      regional lymphadenopathy. Two weeks later, the patient returned complaining of a
      recurrence accompanied by pain and lymphadenopathy. The following day, the
      patient's condition had worsened and the depth of the recession had increased. A
      biopsy was taken for histological examination. A free epithelial-connective
      tissue graft was performed. Histological and direct immunofluorescence
      examinations confirmed the herpetic origin of the lesion. Eight months after
      surgery, a new herpetic lesion was detected in correspondence to the gingival
      margin of the first lower right premolar; therefore, acyclovir was prescribed.
      After 1 week, the antiviral therapy was completely successful; the gingival
      lesion disappeared, and no recession of the soft tissue margin was observed.
      Based on these clinical features, diagnosis of gingival recession induced by HSV
      1 must be carried out at an early stage to establish a successful therapy.

PMID- 11846192
TI  - Treatment of gingival overgrowth induced by manidipine administration. A case
      report.
AB  - BACKGROUND: It is well known that severe gingival overgrowth (GO) is induced in
      patients taking certain calcium channel blockers (CCB) for the treatment of
      hypertension, angina pectoris, and other diseases. No case has been reported to
      date of severe GO induced by manidipine hydrochloride (manidipine), a second
      generation CCB. This case report describes severe GO induced by manidipine in a
      female patient (43 years old) with hypertension and Sjogren syndrome (SS). The
      patient was administered manidipine and carteolol hydrochloride (carteolol) as
      antihypertensive drugs, together with bromhexine hydrochloride for the treatment
      of SS. METHODS: At the initial periodontal examination, probing depth (PD,
      average 4.83 mm), plaque control record (PCR, 84.3%), bleeding on probing (BOP,
      100%), and gingival overgrowth index (GOI, 2.42) were assessed. The patient
      received periodontal treatment without cessation or replacement of the causative
      drug. Initial treatment included oral hygiene and scaling and root planing (SRP)
      under local anesthesia. As corrective therapy, remaining pockets were surgically
      removed and fixed bridges placed to establish proper occlusion. RESULTS: Obvious
      reductions in PCR (10.0%), PD (1.93 mm), GOI (0.02), and BOP (4.7%), together
      with a disappearance of GO, were obtained. Salivary secretion was increased after
      the periodontal and prosthetic treatments. Histological features were similar to
      those of nifedipine-induced GO. CONCLUSIONS: This case indicated that manidipine
      may act as a potent inducer of severe GO, and that conventional periodontal
      treatments without a major change of the causative drugs can yield satisfactory
      clinical responses.

PMID- 11846193
TI  - Thirty-six month follow-up of 25 patients treated with combination anorganic
      bovine-derived hydroxyapatite matrix (ABM)/cell-binding peptide (P-15) bone
      replacement grafts in human infrabony defects. I. Clinical findings.
AB  - BACKGROUND: Long-term evaluation of periodontal therapy is important for clinical
      decision making. METHODS: A synthetic cell-binding peptide (P-15) combined with
      anorganic bovine-derived hydroxyapatite bone matrix (ABM) was evaluated as a bone
      replacement graft in human periodontal osseous defects. Following initial
      preparation and reevaluation, flap surgery was performed. A variety of 1-, 2-, 3
      wall bony defects were curetted and root surfaces subjected to mechanical
      debridement only. The bone defects were grafted with ABM/P-15, and the host flaps
      replaced or slightly coronally positioned. Weekly, then monthly deplaquing was
      performed until surgical reentry at 6 to 7 months. Patients were then followed on
      approximate 3-month recalls for 3 years. Twenty-five of the original 31 patients
      qualified for long-term evaluation in that their ABM/P-15 treated sites did not
      receive any additional therapy at the time of reentry. RESULTS: Significant
      clinical changes for the overall group of bony defects included improvement in
      mean clinical attachment level from 5.4 mm at surgery to 4.5 mm at the 6-month
      reentry to 3.8 mm at 3 years. There was also a decrease in mean probing depth
      from 5.3 mm at surgery to 3.1 mm at the 6-month reentry to 2.9 mm at 3 years. The
      mean gingival recession changed from +0.1 mm at surgery to 1.4 mm at the 6-month
      reentry to 0.9 mm at 3 years. All of these differences were at least P <0.05 from
      surgery to the 6-month reentry, and surgery to 3 years, but were not significant
      from reentry to 3 years via repeated measures analysis of variance. CONCLUSIONS:
      These favorable 3-year results with ABM/P-15 suggest that it may have a
      beneficial effect in the long-term clinical management of infrabony defects.
      Further long-term randomized controlled studies are needed to better assess the
      role of ABM/P-15 in long-term healing of periodontal osseous defects.

PMID- 11846194
TI  - Controlled local delivery of tetracycline with polymer strips in the treatment of
      periodontitis.
AB  - BACKGROUND: Several antibacterial agents have been studied as a means to produce
      bactericidal or bacteriostatic activity as an adjunct to mechanical treatment of
      periodontal disease. The primary purpose of this study was to evaluate the
      efficacy of tetracycline strips administered singly or in multiples in
      conjunction with root planing, versus root planing alone, or to an untreated
      control. Secondary purposes were to compare gingival crevicular fluid (GCF)
      volume and GCF concentrations of tetracycline in pockets treated with strips; to
      evaluate strip insertion time; and to compare ease of placement for single or
      multiple strips. METHODS: Using a 4-quadrant design, 4 test teeth in 24 patients
      were treated with either root planing and single strip application; root planing
      and multiple strip application; root planing alone; or an untreated control.
      RESULTS: Single and multiple strip placement resulted in a significant reduction
      in probing depth (P = 0.033) compared to root planing and untreated groups. The
      multiple strip group significantly decreased bleeding on probing (P = 0.05)
      compared to all other treatment groups. There was no treatment effect on GCF;
      however, there was a significant reduction in the GCF volume over time (P =
      0.001). The time required for placement was, on average, 1.9 minutes for single
      strips and 3.25 minutes for multiple strips. CONCLUSIONS: Our data suggest that
      multiple strips are superior to a single strip in reducing bleeding on probing,
      and that local delivery of tetracycline is superior to root planing alone in
      reducing probing depth.

PMID- 11846195
TI  - Periodontopathic bacterial infection in childhood.
AB  - BACKGROUND: Little information is available on periodontopathic bacterial
      infection in childhood. We assessed the prevalence by age of 10 putative
      periodontopathic microorganisms in periodontally healthy children using a
      polymerase chain reaction (PCR) assay. METHODS: Plaque samples were collected
      from the buccal-mesial sulcus of the first molar or second primary molar in the
      right upper quadrant of 144 children (2 to 13 years old, 12 subjects from each
      year of age) who showed negligible periodontal inflammation. Using species
      specific primers of Porphyromonas gingivalis, Bacteroides forsythus, Prevotella
      intermedia, Prevotella nigrescens, Campylobacter rectus, Eikenella corrodens,
      Actinobacillus actinomycetemcomitans, Capnocytophaga ochracea, Capnocytophaga
      sputigena, and Treponema denticola, PCR amplification was performed with
      bacterial genomic DNA from plaque samples. RESULTS: The results indicated that C.
      rectus, E. corrodens, A. actinomycetemcomitans, C. ochracea, and C. sputigena
      were found in about 50% of the plaque samples from all age groups, while B.
      forsythus and P. intermedia were detected less frequently, and P. gingivalis and
      T. denticola were not found. In contrast, the percentage of P. nigrescens
      positive subjects increased with age in primary dentition, and reached about 50%
      at 7 years of age and older. Subject-based analyses suggested that the number of
      bacterial species in the plaque samples increased gradually with age until 5
      years old, and then reached a plateau after the mixed dentition period.
      CONCLUSIONS: The colonization of many putative periodontopathic microorganisms
      can occur quite early in childhood without clinical signs of periodontal disease.
      However, colonization by P. gingivalis and T. denticola was not detected in
      periodontally healthy children.

PMID- 11846196
TI  - Smoking and polymorphisms of the interleukin-1 gene cluster (IL-1alpha, IL-1beta,
      and IL-1RN) in patients with periodontal disease.
AB  - BACKGROUND: Polymorphisms within the interleukin-1 cluster are known to be
      associated with adult periodontal disease. However, interactions of genetic with
      other risk factors, especially smoking, remain questionable. The aim of this
      cross-sectional study was to evaluate the genetic influence on periodontal
      variables in relation to environmental factors. METHODS: One-hundred fifty-four
      (154) Caucasian subjects were clinically and radiographically assessed for their
      periodontal status, their smoking history recorded, and their allelic pattern of
      IL-1alpha, IL-1beta, and IL-1RN polymorphisms determined by genotyping. RESULTS:
      In assessing periodontitis with mean probing depth, mean attachment loss, or mean
      bone loss, no differences were found in allele frequencies or combined allotypes
      between subjects with mild or moderate versus those with severe signs of
      periodontitis. However, the extent of attachment loss defined as percentage of
      sites >4 mm was significantly associated with the composite genotype of IL
      1alpha/1beta in smokers (odds ratio [OR] = 4.00; 95% confidence interval [CI]
      1.03 to 16.70; P= 0.02). No differences were found in genotype negative subjects
      irrespective of their smoking status. They had nearly identical attachment loss
      as genotype positive non-smokers. Similar non-significant results were found with
      respect to extent of bone loss. An increased risk of more extended attachment
      loss was observed also in individuals carrying mutations of the combined genotype
      IL-1alpha/IL-1RN, again showing enhanced risk only in genotype-positive and
      smoking subjects. CONCLUSIONS: The results provide evidence that the composite
      genotypes studied show interaction with smoking, the main exposition-related risk
      factor of periodontal disease. Non-smoking subjects are not at increased risk,
      even if they are genotype-positive.

PMID- 11846197
TI  - Enamel matrix proteins and guided tissue regeneration with titanium-reinforced
      expanded polytetrafluoroethylene membranes in the treatment of infrabony defects:
      a comparative controlled clinical trial.
AB  - BACKGROUND: Several studies have documented the clinical efficacy of guided
      tissue regeneration (GTR) with non-resorbable expanded polytetrafluoroethylene
      (ePTFE) membranes and enamel matrix proteins (EMP) in the treatment of infrabony
      defects. The objective of this controlled clinical study was to compare the
      clinical outcomes of 3 surgical modalities in the treatment of deep interproximal
      infrabony defects. METHODS: Ninety (90) defects in 90 healthy subjects affected
      by chronic periodontitis were assigned to 1 of 3 treatment groups by blocking to
      prognostic variables. The test group was treated with the application of EMP and
      the simplified papilla preservation (SPP) technique; the second group was treated
      with titanium-reinforced ePFTE membranes and the SPP technique; and the third
      group was treated with the SPP technique used as access flap control procedure.
      No differences were observed in terms of baseline oral hygiene and defect
      characteristics among the 3 groups, indicating that the blocking approach was
      effective. A stringent infection control program was adopted for 1 year. RESULTS:
      The 1-year results indicated that: 1) all treatment modalities resulted in
      clinically significant improvements in clinical attachment levels (CAL) and
      reduction in probing depth (PD); 2) a statistically significant treatment effect
      was demonstrated comparing the EMP test, the membrane control, and the flap
      control groups in terms of CAL gains; 3) both the EMP test and the membrane
      control groups showed significant CAL gains compared to the flap control group;
      4) a statistically significantly greater amount of CAL gain was demonstrated in
      GTR-treated compared to EMP-treated patients; 5) deeper residual probing depths
      but smaller increases in gingival recession were demonstrated following EMP
      therapy; and 6) smoking habits reduced the clinical outcomes of both regenerative
      procedures. CONCLUSIONS: The use of a regenerative procedure is indicated in the
      treatment of deep vertical bony defects since both the regenerative techniques
      (GTR and EMD) in the present study resulted in clinically and statistically
      significant improvements in clinical parameters compared to the access flap
      procedure. The use of EMP can be helpful in esthetically-sensitive sites and in
      reducing patient morbidity.

PMID- 11846198
TI  - Itraconazole prophylaxis for invasive gingival aspergillosis in neutropenic
      patients with acute leukemia.
AB  - BACKGROUND: Due to an increasing number of leukemic patients with invasive
      gingival aspergillosis during neutropenia (neutrophils <500 cells/microl for >10
      days), we evaluated the efficacy of oral itraconazole prophylaxis for preventing
      this invasive infection at our hospital. METHODS: This was a retrospective, non
      randomized study to analyze the onset of identified invasive gingival
      aspergillosis among 536 patients with acute leukemia at risk due to the presence
      of neutropenia from 1991 to 1998. Patients received itraconazole capsules 100
      mg/day prophylactically between April 1994 and December 1996, and 200 mg/day
      between January 1997 and December 1998. Itraconazole serum levels at day 10 were
      measured in some patients. RESULTS: In the 39 months prior to April 1994 without
      itraconazole prophylaxis, 15 cases of invasive gingival aspergillosis were
      detected in 192 high risk patients with 469 episodes of neutropenia (7.8% of the
      high risk patients). Between April 1994 and December 1996, using itraconazole
      prophylaxis at 100 mg/day, there was a dramatic decrease in the infections
      resulting in 3 of 198 high risk patients with 511 episodes of neutropenia (1.5%
      of the high risk patients). Furthermore, between January 1997 and December 1998,
      using itraconazole prophylaxis at 200 mg/day, no cases of the infection were
      observed in the 146 high risk patients with 380 episodes of neutropenia. The
      incidence of invasive gingival aspergillosis was significantly lower among
      patients administered itraconazole than among those without itraconazole (100
      mg/day; P = 0.006 and 200 mg/day; P = 0.001). The mean itraconazole serum level
      in 20 patients receiving 100 mg/day was 71.78 ng/mL and in 16 patients receiving
      200 mg/day was 202.67 ng/ml. CONCLUSIONS: These findings suggest that oral
      itraconazole could be effective for preventing invasive gingival aspergillosis in
      neutropenic patients with acute leukemia and warrants further randomized
      investigation.

PMID- 11846199
TI  - Sinus floor augmentation at the time of maxillary molar extraction: success and
      failure rates of 137 implants in function for up to 3 years.
AB  - BACKGROUND: Implant restoration of the posterior maxilla poses significant
      challenges to the clinician. In an effort to increase the apical occlusal
      dimension of available bone for implant placement, a number of sinus augmentation
      approaches have been suggested. This paper describes a simplified technique for
      predictable sinus augmentation at the time of maxillary molar extraction.
      METHODS: A modified trephine and osteotome technique was utilized to implode the
      interradicular bone following maxillary molar extraction. Particulate material
      and a membrane were then placed to maximize regeneration of alveolar bone.
      RESULTS: One hundred sixty-seven (167) implants were subsequently placed in
      regenerated bone following the above technique. One hundred thirty-seven (137) of
      these implants were restored and in function for up to 3 years at the time of
      statistical compilation, and 136 of the 137 implants were functioning
      successfully by the Albrekteson criteria for a cumulative success rate of 97.8%.
      CONCLUSIONS: The technique presented for simultaneous sinus augmentation at the
      time of molar extraction, followed by subsequent implant placement after
      maturation of regenerating tissues, demonstrates a high success rate for up to 3
      years in function. Long-term studies may be useful in evaluating the continual
      efficacy of such an approach.

PMID- 11846200
TI  - Lamina propria dendritic cells express activation markers and contact lymphocytes
      in chronic periodontitis.
AB  - BACKGROUND: Dendritic cells are characterized by shape, structure, and membrane
      molecule expression; they contact T lymphocytes to present antigens and stimulate
      plasma cell differentiation in vitro. Dendritic cells are known to be present in
      healthy human gingiva and to be altered in HIV-associated periodontitis. Here, we
      address the phenotype, location, and intercellular relationships of dendritic
      cells in chronic periodontitis. METHODS: Biopsies from patients with chronic
      periodontitis were analyzed by electron microscopy and indirect
      immunofluorescence for dendritic cells and lymphocyte markers. RESULTS:
      Langerhans' cells were spread in oral epithelium but restricted to the basal
      layer in pocket epithelium; they did not usually express major histocompatibility
      complex (MHC)-II antigens nor contact lymphocytes. Dendritic cells were abundant
      in the lamina propria of pocket epithelium; they were MHC-II positive, admixed
      with CD4-positive and CD8-positive T lymphocytes, and, they expressed CD54, CD80,
      and CD86. Dendritic cells often contacted lymphocytes and were also located
      within plasma cell aggregates. CONCLUSIONS: The data suggest that prerequisites
      for mounting a T cell-mediated immune response exist in chronic periodontitis,
      although this response is limited to the lamina propria. These results suggest
      that T-cell responses offer limited protection and can contribute to tissue
      damage during periodontal disease.

PMID- 11846201
TI  - Treatment of gingival recessions by combined periodontal regenerative technique,
      guided tissue regeneration, and subpedicle connective tissue graft. A comparative
      clinical study.
AB  - BACKGROUND: Many surgical techniques have been shown to be effective in
      correcting gingival recessions by covering the exposed root with soft tissue;
      however, the thickness of the gingival tissue over the root surface probably
      plays an important role in preventing the recurrence of tissue recession. The aim
      of the present study was to compare the results of a mucogingival bilaminar
      technique (BT), guided tissue regeneration (GTR), and a combined periodontal
      regenerative technique (CPRT) in achieving root coverage and increasing the
      gingival thickness 1 year after surgical treatment. METHODS: In 45 systemically
      healthy, non-smoking patients aged 33.6 +/- 4.3 years with no periodontal pockets
      >4 mm, a Miller's Class I or II gingival recession was treated for root coverage:
      15 patients underwent BT (connective tissue with partial-thickness double pedicle
      graft), 15 GTR by a bioabsorbable membrane, and 15 CPRT by a collagen membrane
      and collagen-incorporated hydroxyapatite. Before and 1 year after surgical
      treatments, the following clinical parameters were recorded: gingival recession
      (GR), probing depth (PD), clinical attachment level (CAL), keratinized tissue
      width (KT), and gingival thickness (GT); the percentage of root coverage was also
      calculated and the data were statistically analyzed. RESULTS: All 3 techniques
      yielded significant improvements in terms of GR decrease, CAL and KT gain, and GT
      increase compared to baseline values. Mean root coverage was 90.0%, 81.01%, and
      87.12% in BT, GTR, and CPRT groups, respectively. Complete root coverage was
      observed in 60%, 40%, and 53.3% of subjects from the BT, GTR, and CPRT groups,
      respectively. No significant differences were observed among the 3 techniques in
      GR or CAL improvements; however, BT produced a significantly (P<0.01) greater
      increase of KT, and BT and CPRT groups showed a significantly (P<0.01) greater
      increase of GT compared to the GTR group. CONCLUSIONS: BT, GTR, and CPRT
      successfully treated gingival recession defects, obtaining comparable percentages
      of root coverage, but BT and CPRT created a thick gingival tissue significantly
      greater than that achieved with GTR.

PMID- 11846202
TI  - Systemic release of endotoxins induced by gentle mastication: association with
      periodontitis severity.
AB  - BACKGROUND: Periodontitis has recently been identified as a potential risk factor
      for systemic pathologies such as cardiovascular disease, the hypothesis being
      that periodontal pockets could release pro-inflammatory bacterial components, for
      instance endotoxins, into the bloodstream. It is known that the oral cavity can
      be a source of circulating bacteria, but this has never been shown for bacterial
      endotoxins, and no evidence exists so far that the risk of systemic injury is
      related to the severity of periodontitis. The aim of the present study was to
      test the influence of gentle mastication on the occurrence of endotoxemia in
      patients with or without periodontal disease. METHODS: A total of 67 subjects
      were periodontally examined and grouped according to their periodontal status.
      This classification was based on an original index of severity of periodontal
      disease (periodontal index for risk of infectiousness, PIRI) aimed at reflecting
      the individual risk of systemic injury from the periodontal niches. Thus, the
      patients were classified into 3 risk groups: low, PIRI = 0; n = 25; moderate, 1 <
      or = PIRI < or = 5, n = 27; and high 6 < or = PIRI < or = 10, n = 15. Blood
      samples were collected before and 5 to 10 minutes after a standardized session of
      gentle mastication for detection of circulating endotoxins. Blood samples were
      tested with a chromogenic limulus amoebocyte lysate assay. RESULTS: Overall,
      blood levels of endotoxin after mastication were found to be significantly higher
      than before mastication (0.89 +/- 3.3 pg/ml versus 3.0 +/- 5.8 pg/ml; P= 0.0002).
      Likewise, the incidence of positive endotoxemia rose from 6% before mastication
      to 24% after mastication (P = 0.001). When accounting for the PIRI index,
      endotoxin levels and positive endotoxemia proved to be significantly higher in
      patients with severe periodontal disease than in the subjects with low or
      moderate periodontitis. CONCLUSIONS: Gentle mastication is able to induce the
      release of bacterial endotoxins from oral origin into the bloodstream, especially
      when patients have severe periodontal disease. This finding suggests that a
      diseased periodontium can be a major and underestimated source of chronic, or
      even permanent, release of bacterial pro-inflammatory components into the
      bloodstream.

PMID- 11846203
TI  - Inhibition of proteolytic, serpinolytic, and progelatinase-b activation
      activities of periodontopathogens by doxycycline and the non-antimicrobial
      chemically modified tetracycline derivatives.
AB  - BACKGROUND: Tetracyclines, particularly doxycycline (Doxy), and their non
      antimicrobial chemically-modified derivatives (CMTs) inhibit the activities of
      human matrix metalloproteinases (MMPs), and reduce the severity and progression
      of periodontal disease in animal models and humans. In this study, the effects of
      Doxy and CMT-1, -3, and -5 on proteolytic, serpinolytic, and progelatinase-B
      activation activities of potent periodontopathogens were studied. METHODS: The
      effect of Doxy and CMTs (0.5 to 50 microM) on proteolytic activities were
      investigated by incubating bacteria with chromogenic substrates or human serum
      albumin. A collagenolytic fraction of Porphyromonas gingivalis was used to
      evaluate the effect of these substances on collagenolytic (type I collagen) and
      serpinolytic (alpha1-proteinase inhibitor) activities. Lastly, the effect of Doxy
      on progelatinase-B (pro-MMP-9) activation by purified proteinases from P.
      gingivalis and Treponema denticola was investigated by SDS-PAGE/Western
      immunoblotting. RESULTS: Doxy and CMTs, except CMT-5 which lacks the structural
      elements required for cation chelation, inhibited Arg- and Lys-gingipain
      activities as well as collagenolytic activity of P. gingivalis. Doxy and CMTs did
      not markedly affect the chymotrypsin-like activity of T. denticola but inhibited
      its trypsin-like activity. In addition, degradation of human serum albumin by
      cells of P. gingivalis and T. denticola was strongly inhibited by Doxy and CMT-1.
      Doxy and CMT-1 also inhibited the inactivation of alpha1-proteinase inhibitor
      (serpinolytic activity) by a collagenolytic fraction of P. gingivalis. Lastly,
      Doxy prevented the latent to active conversion of human neutrophil progelatinase
      B (pro-MMP-9) by Arg-gingipains A/B of P. gingivalis but not by the chymotrypsin
      like proteinase of T. denticola. CONCLUSIONS: Data from this study suggest that
      Doxy and CMTs have the potential to inhibit the periodontopathogenic bacterial
      proteinases, which contribute to tissue destruction cascades during periodontitis
      directly and indirectly by triggering the host response.

PMID- 11846204
TI  - An organotypic in vitro model that mimics the dento-epithelial junction.
AB  - BACKGROUND: The dento-epithelial junction forms the primary periodontal defense
      structure against oral microbes. The cells of the junctional epithelium (JE)
      attach both to a basement membrane (BM) facing the connective tissue and to a
      hard dental tissue by structurally similar but molecularly distinct mechanisms.
      Here we describe a new organotypic cell culture model for the dento-epithelial
      junction comprising not only epithelial and mesenchymally derived components, but
      also a tooth surface equivalent. METHODS: Rat palatal keratinocytes were seeded
      on fibroblast-collagen gels. A tooth slice was placed on top of the epithelial
      cells and the multilayer cultures were grown at the air-liquid interface.
      Formation of the epithelial structures, BM components, and the epithelial
      attachment to the tooth surface were studied by immunofluorescence and light and
      electron microscopy. The findings were compared to the structure of the dento
      epithelial junction in vivo. RESULTS: A well-differentiated stratified epithelium
      was formed. Under the tooth slice the epithelium remained thin and non
      differentiated. Attachment of the epithelial cells to the tooth surface was
      mediated by hemidesmosomes (HDs) as in vivo. Laminin-5 (Ln-5) was present in the
      extracellular matrix (ECM) between the tooth and the epithelium as well as in the
      BM structure between the epithelium and the fibroblast-collagen matrix. Instead,
      Ln-10/11 was present only at the mesenchymal tissue side as is known to be the
      case in vivo. CONCLUSIONS: The organotypic model presented expresses the
      characteristic structural and molecular features of the dento-epithelial junction
      and may be applied for studying physiological and pathological processes in the
      epithelial attachment.

PMID- 11846205
TI  - Histological comparison of healing extraction sockets implanted with bioactive
      glass or demineralized freeze-dried bone allograft: a pilot study.
AB  - BACKGROUND: Various materials have been used immediately following tooth
      extraction to fill and/or cover the socket in an attempt to limit or prevent
      ridge resorption. The purpose of the present pilot study was to establish a
      reliable model to investigate the effect of various bone graft and bone
      replacement materials on extraction socket healing. This study also compared
      healing extraction sockets 6 to 8 months postimplantation of a bioactive glass
      (BG) or demineralized freeze-dried bone allograft (DFDBA) to an unfilled socket
      control (C). METHODS: Following tooth extraction, a total of 30 sockets in 19
      patients were randomly divided into 3 treatment groups: 10 sockets received BG,
      10 sockets DFDBA, and 10 sockets served as unfilled controls. Primary coverage
      was achieved by flap advancement over each socket. Six to 8 months postextraction
      at time of implant placement, histological cores of the treatment sites were
      obtained. These cores were processed, undecalcified sections prepared and stained
      with Stevenel blue/van Gieson's picric fuchsin, and histomorphometrically
      analyzed. Vital bone, connective tissue and marrow, and residual graft particles
      were reported as a percentage of the total core. RESULTS: A model system was
      described in humans and used to evaluate the healing response in the 3 treatment
      groups. Results concluded that mean vital bone present was 59.5% for BG-, 34.7%
      for DFDBA-, and 32.4% for C-treated sites. These differences were not
      statistically significant. However, the residual implant material was
      significantly higher in DFDBA-treated (13.5%) versus BG-treated sockets (5.5%).
      CONCLUSIONS: Although the differences in percent vital bone were not
      statistically significant among the 3 treatment groups in this pilot study, BG
      material was observed to act as an osteoconductive material which had a positive
      effect on socket healing at 6 to 8 months postextraction. Further research
      following implant placement in treated and control sockets is warranted to
      determine if bone implant contact is improved in BG-filled versus unfilled
      sockets.

PMID- 11846206
TI  - Quantitative analysis of gene expressions of vascular endothelial growth factor
      related factors and their receptors in renal cell carcinoma.
AB  - Vascular endothelial growth factor (VEGF)-related factors are believed to
      regulate angiogenesis, an essential event in the growth of solid tumors. In this
      study, we investigated the expression of VEGF-related factor genes (VEGF, VEGF-B,
      and VEGF-C) and their receptor genes (VEGFR-1 and VEGFR-2) in renal cell
      carcinoma (RCC). There were significant differences in the expression level of
      VEGF, VEGFR-1 and VEGFR-2 between RCC and the corresponding normal renal tissue.
      The expression level of VEGF in the tumor tissue significantly correlated with
      those of VEGFR-1 and VEGFR-2. Expression levels VEGF-B and VEGF-C genes were not
      significantly different between RCC and normal renal tissue. A moderate to high
      protein expression for VEGF, VEGFR-1, and VEGFR-2 was observed in both the tumor
      cells and the endothelial cells, whereas the protein expression was low for VEGF
      B and VEGF-C. The present results suggested that VEGF and its receptors VEGFR-1
      and VEGFR-2 cooperates to play a crucial role in the angiogenesis of RCC, while
      VEGF-B and VEGFR-C may not. Furthermore, since VEGFR-1 and VEGFR-2 proteins were
      expressed in the tumor cells as well as in the endothelial cells, these receptors
      may also be responsible for the progression of RCC.

PMID- 11846207
TI  - Age-related changes in fatty acid composition in muscles.
AB  - Changes in lipid metabolism in muscles are closely related to insulin resistance.
      Insulin resistance is impaired during aging in hereditary hypertriglyceridemic
      rats. However, changes in the membrane fatty acid composition during aging are
      poorly understood. The aim of the study was to describe the fatty acid (FA)
      composition of muscle phospholipids in the diaphragm and in the m. soleus in
      relation to aging and insulin resistance. Female hereditary hypertriglyceridemic
      rats (HHTg) have been shown to have elevated levels of serum triglycerides.
      Fasting and post-load blood glucose and insulin concentrations were higher in
      HHTg lines as compared with controls of the same age. The most important changes
      observed in the m. soleus in the HHTg line included decreased saturated FA
      between 3 and 14 months of age (42.79 +/- 2.30 vs. 28.85 +/- 2.57mol.%, p<0.01)
      and increased polyunsaturated FA n-6 (27.99 +/- 1.66 vs. 39.37+2.29 mol.%,
      p<0.01). In the diaphragm we noted, in normotriglyceridemic controls, increased
      proportions of monounsaturated FA (5.73 +/- 0.80 vs. 11.02 +/- 0.75mol.%,
      p<0.001), while these proportions were decreased in HHTg rats (13.50 +/- 0.83 vs.
      10.46 + 0.61 mol.%, p < 0.05). Age-related changes in muscle phospholipids seem
      not to be the key to explaining insulin resistance.

PMID- 11846208
TI  - Appraisal of intra-arterial infusion of prostaglandin E1 in patients undergoing
      major hepatic resection report of four cases.
AB  - In order to reduce risk for postoperative acute liver failure, prostaglandin E1
      (PGE1) was administered either from the hepatic artery (HA) or the superior
      mesenteric artery (SMA) in four high-risk cases undergoing major hepatic
      resection. Two cases were subjected to HA PGE1 infusion for 3 or 4 days after
      surgery at a rate of 0.01 microg/kg/min. Both patients had hepatocellular
      carcinoma (HCC) associated with chronic hepatitis, and ICG R15 was 17.6% and
      14.5%, respectively. Right hemihepatectomy and extended right hemihepatectomy
      were performed. Serum total bilirubin (T. Bil.) peak value was 2.2 mg/100 ml in
      Case 1 and 2.1 mg/100 ml in Case 2. In Case 1, decreased bile flow was observed
      immediately after cessation of PGE1. The other two cases were subjected to SMA
      PGE1 infusion for 5 or 6 days after surgery at the same rate. In Case 3, right
      hemihepatectomy was performed for HCC on a cirrhotic liver four weeks after right
      portal vein embolization, in which preoperative ICG R15 was 19.0%. Peak T. Bil
      level was 3.7 mg/100 ml with uneventful postoperative course. In Case 4 with a
      huge cholangioma, right trisegmentectomy was performed. Peak serum T. Bil level
      was 1.7 mg/100 ml in this uneventful postoperative course. In Case 3 and Case 4,
      portal blood flow, measured by Doppler ultrasonography, was markedly increased by
      PGE1 infusion. From these results, intra-arterial PGE1 infusion might be useful
      in prevention of postoperative liver failure after major hepatic resection.

PMID- 11846209
TI  - Two cases of Japanese CADASIL with corpus callosum lesion.
AB  - Cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leucoencephalopathy (CADASIL) is a rare hereditary stroke disease. In the present
      study, a Japanese CADASIL family was first reported with missense mutation of
      Arg141Cys of Notch3 and a unique lesion of corpus callosum. Upon
      neuropsychological examination, our case 1 showed only right-handed
      constructional apraxia associated with corpus callosum lesion. No other callosal
      disconnection signs were present. Sagittal T2 weighted image of case 1 showed
      multiple small lesions along with the pericallosal branches from the truncus to
      the posterior part of the splenium in the corpus callosum. Although detailed
      mapping of the corpus callosum for functional fractionation in humans remains
      incomplete, the constructional apraxia on the right may be related to callosal
      dysfunction from the truncus to the posterior part of the splenium in the corpus
      callosum.

PMID- 11846210
TI  - Evaluation of tube compensation in the Bennett 840 ventilator--a new ventilatory
      mode to support spontaneous breathing.
AB  - Respiratory care patients frequently require intubation with an endotracheal tube
      (ETT). Unfortunately, the ETT introduces a pressure drop (deltaPETT) that depends
      on the respiratory flow rate, thus increasing the work of breathing (WOB).
      Pressure support ventilation (PSV) cannot adequately compensate for this added
      WOB, because the degree of inspiratory assistance by PSV is fixed. Therefore, a
      technique called tube compensation (TC) has been developed to address deltaPETT.
      We examined the performance of TC and compared it with PSV of 5 cm H2O. The
      experimental system was constructed from a simulator, a test-lung, flow sensors,
      and a Bennett 840, and the respiratory parameters were studied. ETTs with IDs 6.5
      and 8.0 mm were used. The quadratic approximation obtained for deltaPETT in the
      6.5-mm ETT was 2.316 x flow + 7.910 x flow2, while that for the 8.0-mm ETT was
      1.881 x flow + 3.353 x flow2. The maximum inspiratory flow (MIF) increased
      significantly with increasing TC, but tidal volume and inspiratory time did not
      show marked changes. The MIF for TC of 100% was larger than that for PSV of 5 cm
      H2O, when the 6.5-mm ID was used, but there was no significant difference between
      these modes when an ID of 8.0 mm was used. For both the 6.5 and 8.0-mm IDs, the
      PV loop corresponding to 100% TC was larger than that for PSV of 5 cm H2O. TC
      only compensated for the WOB caused by the ETT, whereas PSV compensated for the
      WOB caused by the ETT and the demand valve system. In clinical use, the
      differences between TC and PSV will demand attention.

PMID- 11846211
TI  - Improved survival of children with advanced neuroblastoma treated by intensified
      therapy including myeloablative chemotherapy with stem cell transplantation: a
      retrospective analysis from the Tohoku Neuroblastoma Study Group.
AB  - In the hospitals of the Tohoku Neuroblastoma Study Group (TNBSG), treatment for
      children with advanced neuroblastoma (NB) was intensified in the mid-1990's with
      the introduction of myeloablative therapy (MT) with stem cell transplantation
      (SCT) including the use of autologous peripheral blood stem cells (PBSC) and bone
      marrow transplantation (BMT). In this report, we examined whether the intensified
      therapy improved the outcome of children with advanced NB (age> 12 months) who
      were diagnosed between 1991 and 1997. Patients were 36 children (23 boys and 13
      girls) with an average age of 3.4 years (range; 1 to 14 years). Six of them had
      stage III disease, and the other 30 had stage IV. They were treated initially
      with induction chemotherapy, surgery, and post-operative chemoradiotherapy, after
      which 17 of them continued further chemotherapy and the other 19 received MT/SCT
      (18 with PBSCT and 1 with BMT). Progression-free survival (PFS) rate at seven
      years from diagnosis was 43.5% for all patients, 66.7% for stage III patients and
      38.2% for stage IV patients. The difference between stage III and IV patients was
      not significant. Among the 30 patients with stage IV disease, PFS at seven years
      was significantly higher in the 19 patients who received MT/SCT (55.6%) than in
      the 11 patients who did not receive it (12.5%). There was no difference in
      clinical and biological risk factors between these two groups, except for the
      proportion of patients with favorable response to initial therapy (36% and 80%
      for patients without and with MT/SCT, respectively). Furthermore, the proportion
      of patients with N-myc amplification was significantly higher in patients with
      progressive disease (PD) after MT/SCT than in those in CR after MT/SCT. The
      results of this retrospective study of children with advanced NB suggest that
      therapy intensification involving MT/SCT might result in lengthened survival time
      for patients with stage IV disease, and that post-transplant PD remains a risk
      for patients with high levels of N-myc amplification.

PMID- 11846212
TI  - Incidence of genetic subgroups of hereditary spinocerebellar ataxia in Fukushima
      Prefecture.
AB  - The prevalence of each type of hereditary spinocerebellar ataxias (SCAs) was
      genetically determined in Fukushima Prefecture, and the results were compared to
      those in other areas of Japan. The genetic analyses were done in 29 patients with
      dominant SCA and 5 patients with SCA with negative family history. Machado-Joseph
      disease was identified in 41.3% of the cases, SCA6 17.2%, dentatorubral
      pallidoluysian atrophy (DRPLA) 6.9% and unknown 34.5%. The incidence is clearly
      different from those of Miyagi and Yamagata Prefectures as SCA1 has not been
      identified in our region, and is in fact similar to that of Hokuriku or Kanto
      Provinces. An apparent difference in the incidence of each SCA may be attributed
      to the historical and geographic regional difference in the distribution of
      inhabitants and also to the small size of the SCA population we have so far
      investigated. In addition, 2 of the 3 genetically identified DRPLA in this study
      were not clinically diagnosed, and one of them was thought to be sporadic. Late
      onset DRPLA may thus be misdiagnosed to other disease categories, when dementia
      was not apparent at the time of onset.

PMID- 11846213
TI  - Stiffness index of the calcaneus measured by quantitative ultrasound and
      menopause among Japanese women: The Hizen-Oshima Study.
AB  - Quantitative ultrasound (QUS) is a recently developed technique for evaluating
      fracture risk that can assess both bone mass and architecture. Although numerous
      studies have shown that menopause is associated with accelerated loss of bone
      mineral density, there are only a few studies on the association of QUS parameter
      (stiffness index) with menopausal status, especially among Japanese population.
      We examined age-specific changes in stiffness index, and relation with age, body
      mass index (BMI) and menopausal status among 506 community-dwelling Japanese
      women aged 40-89 years. Mean age at menopause (standard deviation) among 459
      women with natural menopause was 49.4 (4.0) years. Stiffness index significantly
      decreased with increasing age. Stiffness index among 80-89 years age group was
      40% lower, compared with that of 40-49 years age group. The greatest decline
      among adjacent ten-year age groups in stiffness index (15%) was found between 40
      49 and 50-59 years of age. Multiple regression analysis showed that menopause
      related with decreased stiffness index, independent of age and BMI. Our findings
      indicate that menopause influences loss of bone mass and induces deterioration of
      bone trabecular microstructure.

PMID- 11846214
TI  - The nature of chromosomal aberrations detected in humans exposed to benzene.
AB  - Benzene is an established cause of human leukemia that is thought to act by
      producing chromosomal aberrations and altered in cell differentiation. In several
      recent studies increased levels of chromosomal aberrations in peripheral blood
      lymphocytes were correlated with a heightened risk of cancer, especially
      hematological malignancies. Thus, chromosomal aberrations may be a predictor of
      future leukemia risk. Previous studies exploring whether benzene exposure induces
      chromosomal aberrations have yielded mostly positive results. However, it remains
      unclear whether the chromosomal aberrations induced by benzene occur in a
      distinct pattern. Here, we thoroughly review the major chromosome studies
      published to date in benzene-exposed workers, benzene-poisoned and preleukemia
      patients, and leukemia cases associated with benzene expose. Although three
      cytogenetic markers (chromosomal aberrations, sister chromatid exchanges, and
      micronuclei) are commonly examined, our primary focus is on studies of
      chromosomal aberrations, because only this marker has so far been correlated with
      increased cancer risk. This review surveys the published literature, analyzes the
      study results, and discusses the characteristics of effects reported. In most
      studies of currently exposed workers, increases in chromosomal aberrations were
      observed. However, due to the relatively small number of affected individuals and
      variability in the reported aberrations, firm conclusions cannot be made about
      the involvement of specific chromosomes or chromosome regions. Further, in
      leukemia cases associated with benzene exposure, there is no evidence of a unique
      pattern of benzene-induced chromosomal aberrations in humans. Leukemia cases
      associated with benzene exposure are, however, more likely to contain clonal
      chromosome aberrations then those arising de novo in the general population.

PMID- 11846215
TI  - Binding properties of the mannose receptor.
AB  - A comprehensive approach to the study of mannose receptor (MR) biology has
      unveiled an unexpected level of complexity and stresses the importance of post
      translational modifications and gene regulation in the analysis of protein
      function. The existence of endogenous tissue ligands for the MR highlights the
      need to reduce MR expression in antigen presenting cells and/or to regulate T
      cell stimulation after presentation of MR ligands, in order to avoid
      autoimmunity. This regulation might be achieved by down modulation of the antigen
      presenting cell stimulatory capacity upon MR ligation. In macrophages there are
      conflicting evidence regarding the outcome of MR recognition. These results are
      not unexpected if endogenous mannosylated and sulphated self-antigens, that need
      to be shielded from the immune system, are being eliminated through this
      receptor. The presence of counter receptors for the cysteine rich (CR) domain of
      the MR in specialized myeloid cells in lymphoid organs adds a new dimension to
      this system. It opens the possibility for a delivery pathway for MR carbohydrate
      recognition domains (CRDs) ligands that needs to be investigated further.

PMID- 11846216
TI  - Regulation of the chemokine system at the level of chemokine receptor expression
      and signaling activity.
AB  - The chemokine system is highly influenced by the microenvironmental context.
      Regulation of the chemokine system occurs not only at the level of agonist
      production, but also at the level of chemokine receptor expression. This review
      provides examples of regulation of the system at the receptor level by modulation
      of receptor expression in canonical cellular targets (tuning of the system), and
      induction of novel receptors (shaping of the system), with particular attention
      to dendritic cells as a cellular model. Receptor signaling activity represents a
      further potential level of regulation of the system. Finally, chemokines can also
      influence the microenvironment by modulating gene expression in target cells.

PMID- 11846217
TI  - Molecular mechanisms involved in macrophage survival, proliferation, activation
      or apoptosis.
AB  - Macrophages play a critical role during the immune response. Like other cells of
      the immune system, macrophages are produced in large amounts and most of them die
      through apoptosis. Macrophages survive in the presence of soluble factors, such
      as IFN-gamma, or extracellular matrix proteins like decorin. The mechanism toward
      survival requires the blocking of proliferation at the G1/S boundary of the cell
      cycle that is mediated by the cyclin-dependent kinase (cdk) inhibitor, p27kip and
      the induction of a cdk inhibitor, p21waf1. At the inflammatory loci, macrophages
      need to proliferate or become activated in order to perform their specialized
      activities. Although the stimuli inducing proliferation and activation follow
      different intracellular pathways, both require the activation of extracellular
      signal-regulated kinases (ERKs) 1 and 2. However, the kinetics of ERK-1/2
      activation is different and is determined by the induction of the MAP-kinase
      phosphatase-1 (MKP-1) that dephosphorilates ERK-1/2. This phosphatase plays a
      critical role in the process of proliferation versus activation of the
      macrophages.

PMID- 11846218
TI  - Regulation of Th1/Th2 development by antigen-presenting cells in vivo.
AB  - The aim of this work was to test whether the nature of the antigen-presenting
      cell influences the Th1/Th2 balance in vivo. Adoptive transfer of dendritic cells
      or macrophages, pulsed extracorporeally with antigen, results in antigen-specific
      T cell priming. Of note, macrophages and dendritic cells appear to differentially
      regulate the development of T lymphocytes. In addition, the population of splenic
      dendritic cells appears heterogeneous and includes the CD8alpha+ and CD8alpha-
      subclasses which direct the differentiation of Th1 and Th2 cells, respectively.
      Using neutralizing antibodies and mice genetically deficient for various
      cytokines, we evaluated the role of several molecules in the development of T
      cells in vivo. Our observations emphasize the role of CD86 and IL-6 for Th2
      priming by macrophages, CD86 for Th1 priming by dendritic cells and IL-12 for Th1
      priming by dendritic cells.

PMID- 11846220
TI  - Dendritic cells shuttle microbes across gut epithelial monolayers.
AB  - Understanding the mechanisms governing the type of induced immune response after
      microbial invasion, could be of crucial importance for the rational design of a
      bacteria-based vaccine. Targeting a vaccine directly to dendritic cells (DCs),
      which are considered the most powerful antigen presenting cells, could be
      extremely effective. Here we describe that CD11b+CD8alpha- dendritic cells are
      involved in the direct bacterial uptake across mucosal surfaces. DCs are widely
      spread in the lamina propria of the gut and are recruited at the site of
      infection. DCs open the tight junctions between epithelial cells, send dendrites
      outside of the epithelium and sample bacteria. Moreover, the integrity of the
      epithelial barrier is preserved because DCs express tight junction proteins, such
      as occludin, claudin 1 and Junctional Adhesion Molecule (JAM) and can establish
      tight junctions-like structures with neighbouring epithelial cells.

PMID- 11846219
TI  - Complex encounters at the macrophage-mycobacterium interface: studies on the role
      of the mannose receptor and CD14 in experimental infection models with
      Mycobacterium avium.
AB  - The initial interactions between mycobacterial cell wall components and receptor
      structures on the surface of macrophages may be critical in determining the
      outcome of infection. They may trigger the ingestion and digestion of
      microorganisms, but they may also promote the intracellular persistence and
      growth of mycobacteria. Using Mycobacterium avium as a model system, three
      approaches of different complexities were used to analyse some structural
      features and some functional consequences of M. avium interacting with the
      macrophage mannose receptor or CD14, a pattern recognition receptor. Binding
      specificities of a recombinant, truncated extracellular portion of the mannose
      receptor were assayed in a novel ELISA-formatted system using viable M. avium
      cells as ligands. Infection with M. avium strains differing in their virulence
      were performed in murine bone marrow-derived macrophages and in mice with a
      targeted deletion of the CD14 gene. These parallel and converging approaches not
      only help define the molecular basis for understanding early events in the
      pathogenesis of mycobacterial infections, but are also necessary to ultimately
      determine the relevance of in vitro findings in the context of actual
      manifestations of disease in vivo.

PMID- 11846221
TI  - The plasticity of dendritic cells at the host/fungal interface.

PMID- 11846222
TI  - Skin dendritic cells in murine cutaneous leishmaniasis.
AB  - Studies of the immunopathogenesis of Leishmania major-induced murine cutaneous
      leishmaniasis provide a framework for understanding the evolution of L. major
      infection of skin in humans and the foundation for rationale vaccine design.
      Experiments in which infection is initiated with "suprap hysiologic" numbers of
      parasites clearly identify Th-derived type I cytokines as essential participants
      in macrophage activation and macrophage nitric oxide production as prerequisite
      for parasite control. Dendritic cells, rather than macrophages, appear to be
      responsible for L. major-specific Th priming in these studies. Recent studies of
      murine cutaneous leishmaniasis in a model system in which infection is initiated
      with lower, more physiologic numbers of parasites confirm many of the important
      findings obtained in "high dose" inoculation models, but important differences
      have been noted. The low dose inoculation model should ultimately provide
      insights into mechanisms that are responsible for dendritic cell recruitment into
      leishmania lesions, mechanisms that facilitate parasite acquisition by skin
      dendritic cells and cellular interactions that eventuate in T cell priming and
      lesion involution.

PMID- 11846223
TI  - Conditioning of dendritic cells by pathogen-derived stimuli.

PMID- 11846224
TI  - The macrophage in HIV infection.
AB  - Macrophages play a key role in several critical aspects of HIV disease. They
      appear to be the first cells infected by HIV and perhaps the very source of HIV
      production when CD4+ cells are markedly depleted in the patient. Macrophages and
      microglial cells are the cells infected by HIV in the CNS. In tonsils and
      adenoids of HIV-infected patients, macrophages fuse into multinucleated giant
      cells that produce copious amounts of virus. Finally, opportunistic pathogens can
      cause an upregulation of HIV production by macrophages, often in the
      multinucleated form.

PMID- 11846225
TI  - Defense against influenza A virus infection: essential role of the chemokine
      system.
AB  - Monocytes/macrophages are highly susceptible to an infection with influenza A
      virus. After infection, de novo virus protein synthesis is detectable but rapidly
      interrupted before completion of the first viral replication cycle. Within 24-48
      hours the infected monocytes die by apoptosis. Before cell death, infected
      monocytes initiate a cell-specific immune response. This includes the
      transcription and subsequent release of TNF-alpha (tumor necrosis factor alpha),
      IL-1beta (Interleukin 1beta), IL-6, type I inferferons and CC chemokines.
      Enhanced cytokine mRNA expression is due to a prolonged mRNA stability and an
      augmented gene transcription. Activation of transcription factors such as NF
      kappaB (nuclear factor kappaB) and AP-1 are involved in activation of cytokine
      mRNA transcription. Infection of monocytes with influenza A virus induces the
      selective expression of mononuclear leukocyte attracting chemokines, such as MCP
      1 (monocyte chemotactic protein 1), MIP-1alpha (macrophage inflammatory protein
      1alpha) and RANTES (regulated upon activation, normal T cell expressed and
      secreted). In striking contrast, the release of the neutrophil-specific
      chemokines IL-8 (interleukin 8) and GRO-alpha (growth stimulatory activity alpha)
      is entirely suppressed. This differentially regulated chemokine expression may
      explain the mononuclear cell infiltrate characteristic for virus-infected tissue.
      Thus, infection of monocytes/macrophages with influenza A virus primes for a
      rapid proinflammatory reaction and induces an enhanced immigration of mononuclear
      cells into infected tissue. Taken together, these mechanisms may prepare the
      infected host for a fast and virus-specific immune response.

PMID- 11846226
TI  - Dendritic cells and HIV infection; immunity with viral transmission versus
      compromised cellular immunity?
AB  - In this commentary we propose that changes in immune activity in HIV 1 infection
      are secondary to two aspects of the function of dendritic antigen presenting
      cells (DC). Firstly DC initiate primary proliferative and cytotoxic T cell
      responses to HIV but disseminate virus to T cells. Secondly, balanced against the
      development of protective immunity is progressive inhibition of the capacity of
      DC to initiate primary T cell responses. With regard to viral transmission via
      DC, recent studies provide direct evidence that virus has evolved in vivo by
      passage between DC and T cells and that DC can act as a reservoir for virus.
      Thus, phylogenetic trees of the sequences of V3 loops of HIV viruses in
      individual blood samples show evolution via DC and T cells, and plasma virus can
      be related preferentially to that derived from DC. In functional studies, DC from
      asymptomatic individuals (lacking lymphadenopathy and without treatment) cause
      low levels of stimulation of allogeneic lymphocytes in the mixed leukocyte
      reaction (MLR). By contrast, lymphocytes from these patients respond to normal
      allogeneic DC. Our recent evidence shows that DC stimulate an MLR by transfer of
      alloantigens to DC of the responder type with subsequent syngeneic stimulation of
      T cells. The failure of T cell stimulation by DC in HIV infection therefore shows
      an incapacity of these DC to transfer antigenic signals to other DC but DC that
      acquire and present antigen directly to stimulate T cells are still functional.
      The latter situation provides encouragement that immunotherapy via DC may be
      feasible. However, DC from HIV infected individuals promote antibody production
      in B cells suggesting that the initial interaction of HIV with DC produces
      autocrine effects on DC populations that promote interaction with B cells rather
      than with T cells. Treatment that pushes the DC back towards stimulating T cells,
      despite increased viral dissemination, may promote protective immunity.

PMID- 11846227
TI  - Consequences of dendritic cell (DC)-immunodeficiency virus interactions:
      chemically inactivated virus as a model for studying antigen presentation and
      virus transmission by primate DCs.
AB  - We have established a model approach to study DC-virus communication, in which
      classically immature and mature DCs can be compared. The striking observation
      that macropinocytically poor mature DCs capture and then internalize whole virus
      particles has substantial implications for both antigen processing and
      presentation as well as cell to cell transmission of virus from DCs to nearby T
      cells (as well as other cell types). Studies are ongoing using this system to
      determine what molecules and mechanisms are involved in virus binding and
      internalization by immature versus mature DCs. Discerning the consequences of the
      differential fates of virus in immature versus mature monocyte-derived DCs should
      provide important information on how virus captured by DCs is processed for
      immune activation versus virus dissemination. While there are many features
      shared by monocyte-derived DCs and DCs directly isolated from blood or tissues,
      there are some important distinctions between these DC subsets and their
      activation stage. These traits have considerable influence on immune activation
      by DCs as well as how the individual DC subset handles an immunodeficiency virus.
      Thus, this approach is ultimately being applied to specific DC subsets,
      especially those found at the body surfaces where the first DC-virus interactions
      most frequently occur in vivo. Utilizing this system, we hope to better
      comprehend the initial events of DC-virus communication to (i) facilitate the
      development of strategies to block these events and prevent the onset of
      infection and (ii) identify how to augment the generation of broad anti-viral
      immunity.

PMID- 11846228
TI  - Measle virus-infected dendritic cells develop immunosuppressive and cytotoxic
      activities.
AB  - Measle virus (MV) infection induces a transient but profound immunosuppression
      characterized by a panlymphopenia which occasionally results in opportunistic
      infections responsible for a high rate of mortality in malnourished children. MV
      can encounter human dendritic cells (DC) in the respiratory mucosa or in the
      secondary lymphoid organs. After a brief presentation of DCs, we review progress
      in understanding the immunobiology of MV-infected DCs that could account for MV
      induced immunosuppression. In addition, we develop the newly described TRAIL
      mediated cytotoxic function of DCs that is turned on by MV infection, but also by
      interferons or double-stranded RNA (poly (I:C)). Finally, we propose a model
      where the measles-associated lymphopenia could be mediated by TRAIL and the
      measles-induced immunosuppression could be transiently prolonged by Fas-mediated
      destruction of DCs.

PMID- 11846229
TI  - Interaction of large DNA viruses with dendritic cells.
AB  - Dendritic cells (DC) with their unique capacity to prime naive T cells are
      crucial in the induction of immunological responses, including anti-tumoral and
      anti-viral immunity. DC based immunotherapies are thus currently considered a
      particularly promising approach for cellular immunotherapy. The cloning of tumor
      associated antigens (TAAs) together with the possibility of manipulating viral
      genomes by biotechnological techniques has sparked the interest of using
      genetically modified viruses to transduce DC in order to achieve antigenic
      expression of TAA with the aim of inducing a protective immune response. An
      increasing number of modified viral vectors has been designed for gene therapy
      purposes and consecutively has been used for the ex vivo transduction of DC. It
      has been shown that viral vectors genetically engineered to express TAA or immune
      modifiers like cytokines or costimulatory molecules can lead to a high level of
      transgene expression. Furthermore, these studies have also revealed that viruses
      have developed several immune evasion mechanisms specifically targeting DC.
      Therefore, analysing the interactions of viruses with DC is crucial for the
      development of new viral vectors suitable for the transduction of DC. In this
      report we describe the interaction of two large DNA viruses, herpes simplex virus
      type 1 (HSV-1) and vaccinia virus (VV), with DC generated from peripheral blood
      mononuclear cells.

PMID- 11846231
TI  - Dendritic cell-based vaccination strategies: induction of protective immunity
      against leishmaniasis.
AB  - The clinical symptoms caused by infections with Leishmania parasites range from
      self-healing cutaneous to uncontrolled visceral disease and depend not only on
      the parasite species but also on the type of the host's immune response.
      Infection of genetically susceptible mice with Leishmania major results in the
      development of disease-promoting T helper cells of type 2 (Th2). On the other
      hand, healing of lesions is dependent on the induction of Th1 cells producing
      interferon-gamma (IFN-gamma). The presence of interleukin 12 (IL-12) is known to
      be crucial for the differentiation of Th1 cells. Whereas IL-12 release and the T
      cell stimulatory functions of macrophages are down-regulated by L. major
      infection, dendritic cells (DC) exposed to L. major readily produce IL-12 and are
      highly potent antigen-presenting cells. Moreover, DC pulsed ex vivo with L. major
      antigen induce protection in otherwise susceptible mice against subsequent
      challenges with the parasites. The protection is long-lasting and correlates with
      a shift of the cytokine expression pattern towards a Th1 response. Thus, DC serve
      as immunomodulators in vivo and can be used as an effective adjuvant for
      vaccination against experimental leishmaniasis. Studies on the ability of DC to
      induce protective immunity to leishmaniasis may have important implications for
      the development of novel strategies for prophylactic and therapeutic
      immunizations against microbial pathogens.

PMID- 11846230
TI  - Antigen expression during murine gamma-herpesvirus infection.
AB  - Gammaherpesviruses (gammaHV) establish a life-long latency in the host and are
      associated with a number of malignant human diseases. It is generally believed
      that T cells play a major role in controlling the initial acute infection and
      subsequently maintaining the virus in a quiescent state. However, the nature of
      the T cell response to gamma-herpesvirus infections is poorly understood. In the
      current report we took advantage of a mouse model of gammaHV infection (murine
      herpesvirus-68, MHV-68) to investigate the T cell response to different phases of
      the infection. Intranasal infection with MHV-68 induces an acute infection in
      lung epithelial cells and long-term latency in B cells. The kinetics of the CD8+
      T cell response to different lytic cycle and latency-associated antigens was
      highly complex and distinct patterns of response could be identified. These
      responses were regulated by multiple factors including differences in temporal
      expression of the relevant antigens, differences in the presentation of antigen
      in different organs, and differential expression of antigen in different types of
      antigen presenting cells. For example, some antigens were expressed at distinct
      phases of the infection and in specific organs or subsets of antigen presenting
      cells. In addition, recent data suggest that in addition to B cells, both
      macrophages and dendritic cells harbor latent MHV-68 infection, adding further
      complexity to their role in controlling the T cell response to this infection.

PMID- 11846232
TI  - CpG-oligonucleotides in vaccination: signaling and mechanisms of action.

PMID- 11846233
TI  - High-field 127I NMR of solid sheelite structures: periodates revisited.
AB  - We report new solid-state 127I NMR results for sheelite periodates, MIO4 (M =
      Na+, K+, Rb+, and NH4+), and for pseudo-scheelite CsIO4 and HIO4. The observed
      127I quadrupole coupling constants were between 1.0 and 43.0 MHz in agreement
      with previous NQR data. In contrast to an early 127I NMR study (S. L. Segel and
      H. M. Vyas, 1980, J. Chem. Phys. 72, 1406), we found that the 127I chemical shift
      anisotropy is negligibly small in sheelite periodates. A small but definite 127I
      chemical shift tensor was observed for pseudo-scheelite CsIO4.

PMID- 11846234
TI  - Residual 31P, 35,37Cl dipolar coupling in 31P MAS spectra of
      chlorocyclophosphazenes.
AB  - In 31P MAS NMR spectra of chlorocyclophosphazenes, characteristic splittings have
      been observed for PCI or PCl2 groups. At different applied magnetic fields, the
      fine structure and total width of the patterns change in a characteristic way,
      demonstrating that the splittings are due to indirect spin-spin and residual
      dipolar interactions with the chlorine nuclei directly bonded to phosphorus. For
      trans-nongeminal N3P3Cl3(NMe2)3 and N3P3Cl6 as examples, the spectra have been
      analyzed to obtain information on chlorine nuclear quadrupole coupling constants
      and 35,37Cl, 3P indirect spin-spin coupling constants. Neglect of these
      interactions may result in misinterpretations of the multiplicity in 3P MAS
      spectra of chlorophosphazenes.

PMID- 11846235
TI  - Solid-state 29Si, 113Cd, 119Sn, and 31P NMR studies of II-IV-P2 semiconductors.
AB  - Solid-state 29Si, 113Cd, 119Sn, and 31P MAS NMR spectra are reported on a series
      of II-IV-P2 compounds. In favorable cases (e.g., high degree of crystallinity,
      low concentration of unpaired electrons), well-defined spectra, with sharp lines
      for each specific nearest-neighbor configuration, are observed; in such cases,
      expected J coupling patterns are also seen. High-resolution solid-state NMR
      studies of this type provide useful information on structure (disorder), doping,
      and electron-mediated coupling in semiconductor systems.

PMID- 11846236
TI  - High-field high-speed MAS resolution enhancement in 1H NMR spectroscopy of
      solids.
AB  - Resolution in 1H NMR spectra of solids can be significantly enhanced with fast
      magic-angle spinning and high magnetic fields. A variable field and spinning
      speed study up to 25 T and 40 kHz shows that the homogeneous line broadening is
      inversely proportional to the product of magnetic field strength and spinning
      speed. The combination of high field and fast speed yields a 1H linewidth
      approaching the intrinsic limit determined by anisotropy of magnetic
      susceptibility. An analysis of the anisotropic magnetic susceptibility line
      broadening is presented.

PMID- 11846237
TI  - Solid state 13C NMR of 30-crown-10 ether and 30-crown-10.4H2O.
AB  - The 13C NMR solution spectra of 30-crown-10 ether and its tetrahydrate show only
      one resonance at all accessible temperatures. In contrast, the solid state 13C
      NMR spectrum of the 30-crown-10.4H2O shows two resonances in the ratio of 4:1,
      separated by 1.2 ppm. In the case of 30-crown-10 itself, six resolvable 13C
      resonances in the ratio of 4:1:1:2:1:1 are observed in the solid with an overall
      chemical shift dispersion of 5 ppm. The remarkably different spectral behavior of
      these two systems in the solid state is discussed in terms of the torsional
      environments of the crystallographically unique carbons and the results of GIAO
      calculations of isotropic 13C shieldings for simpler model compounds. Results of
      dipolar dephased 13C CPMAS spectra indicate that 30-crown-10 does not undergo a
      large amplitude molecular motion, in contrast to earlier results for 18-crown-6.
      Only a small amount of residual intensity is found in the dipolar dephased
      spectrum of 30-crown-10.4H2O, indicating that it also is relatively rigid in the
      solid.

PMID- 11846238
TI  - One- and two-dimensional 15N exchange CP/MAS NMR studies of the structure and
      electronic properties of the intermolecular N-H...N hydrogen bond in imidazole
      crystal.
AB  - The hydrogen bond of the type N-H...N in imidazole crystal has been studied by
      one and two-dimensional 15N exchange CP/MAS NMR measurements as well as the
      powder NMR spectrum. The chemical shift anisotropies for -N= and -N< were
      determined from the powder 1D spectrum. In 2D exchange CP/MAS NMR spectrum, the
      cross peaks between the 15N main resonance peaks for -N= and -N< were observed,
      implying that magnetization exchange between -N= and -N< takes place. The 1D
      exchange CP/MAS NMR measurements determined the exchange rate of magnetization at
      289 K to be 1.3 and 1.5 s(-1) for -N= and -N<, respectively. The proton-driven
      spin-diffusion model interprets the experimental values, and the exchange rate
      depends strongly on the RF power of the proton decoupling field, suggesting that
      the magnetization transfer between -N= and -N< takes place by the 1H-driven spin
      diffusion mechanism.

PMID- 11846240
TI  - Urinary incontinence.

PMID- 11846239
TI  - 27Al multiple-quantum MAS NMR of mechanically treated bayerite (alpha-Al(OH)3)
      and silica mixtures.
AB  - Two-dimensional 27Al multiple-quantum magic angle spinning (MQMAS) NMR
      experiments are used to study mixtures of bayerite (alpha-Al(OH)3) with either
      silicic acid (SiO2.nH2O) or silica gel (SiO2) that have been ground together for
      varying lengths of time. This mechanical treatment produces changes in the 27Al
      MAS and MQMAS NMR spectra that correspond to the formation of new Al species.
      Mean values of the quadrupolar interaction (PQ) and isotropic chemical shift
      (deltacs) are extracted from the two-dimensional 27Al NMR spectra for each of
      these species. The presence of significant distributions of both 27Al quadrupolar
      and chemical shift parameters is demonstrated and the effect of grinding duration
      on the magnitudes of these distributions is discussed.

PMID- 11846241
TI  - Basic assessment of urinary incontinence.

PMID- 11846242
TI  - Enuresis.

PMID- 11846243
TI  - Medication update.

PMID- 11846244
TI  - Coverage of urinary incontinence treatment.

PMID- 11846245
TI  - Liver enzymes as predictors of liver damage due to blunt abdominal trauma in
      children.
AB  - BACKGROUND: Blunt abdominal trauma in children can result in injury to the liver.
      In hemodynamically stable patients, initial evaluation of liver transaminase
      levels may be useful in determining the need for computed tomography (CT).
      METHODS: We reviewed the medical records of 44 hemodynamically stable children
      who had abdominal CT and who also had liver enzyme determinations as the initial
      workup. RESULTS: Liver enzymes were found to be elevated in all but one patient
      with CT confirmed hepatic injury. The sensitivity and specificity of elevated
      liver enzyme levels were 92.9% and 100%, respectively, for predicting liver
      injury. CONCLUSION: When hemodynamically stable pediatric patients with blunt
      abdominal trauma have AST levels >400 and/or ALT levels >250 IU/L, abdominal CT
      is indicated. Children in this study with serum transaminase levels below these
      values were at decreased risk of liver injury.

PMID- 11846246
TI  - Utility of palmtop computers in a residency program: a pilot study.
AB  - BACKGROUND: With advancing technology and flourishing medical information on the
      Internet, we studied the use of palmtop (handheld) computers by internal medicine
      residents. METHODS: At a university-community hospital consortium, nine internal
      medicine residents and their program director participated in an 8-month cohort
      pilot study using palmtop computers with desktop synchronization and Internet
      access capabilities. RESULTS: After 2 months of use, the residents had found a
      variety of uses for palmtop computers, such as the calendar, downloading
      residency-provided medical information, taking lecture notes, using a spreadsheet
      for common formulas, Internet/MEDLINE searching with modem access, infrared file
      transfer, downloading call schedules, and patient tracking. At 8 months, the
      residents were comfortable using palmtops on a daily basis. Technical
      difficulties included cumbersome modem cords, incompatible platforms and
      difficult Internet access at times, finding analog telephone lines in the
      hospital, and synchronization with home computers. CONCLUSION: Palmtop computers
      are useful in the residency setting, and residents are capable of devising ways
      to use palmtops to suit their individual needs.

PMID- 11846247
TI  - Effectiveness and safety of image-directed biopsies: coaxial technique versus
      conventional fine-needle aspiration.
AB  - BACKGROUND: We compared the effectiveness and safety of image-guided biopsies
      done with coaxial guides versus fine-needle aspiration done without coaxial
      guides. METHODS: With the use of hospital computer records and chart reviews, all
      image-guided biopsies done during a 4-year period at our institution were
      assessed for adequacy and complications. For each biopsy, the use of a coaxial
      guide, the site, and the imaging modality were recorded. Adequacy of the biopsy
      and complications were compiled. Success rates were calculated for conventional
      and coaxial biopsies and by modality and site. RESULTS: Coaxial technique reduced
      the number of unsatisfactory biopsies compared with conventional technique in
      extrathoracic sites. The decrease was statistically significant. No major
      complications occurred from extrathoracic biopsies with either technique. No
      difference was found in success rates or complication rates between ultrasound
      guided and CT-guided biopsies using coaxial technique. CONCLUSION: Coaxial
      technique reduces the number of inadequate biopsies in extrathoracic sites,
      without a detectable increase in complications.

PMID- 11846248
TI  - Ocular trauma from paintball-pellet war games.
AB  - BACKGROUND: We studied ocular injuries and visual outcome after blunt trauma from
      paintball pellets. METHODS: We retrospectively reviewed cases of ocular injury
      from paintball pellets occurring over 32 months. RESULTS: Ten cases of ocular
      injury from paintball pellets were recorded. Most patients (9) were injured at
      home or at a friend's home; only 1 was injured at a war game facility. Six
      patients had surgery. Final visual acuity was 20/25 or better in 6 patients,
      20/30 to 20/50 in 2 patients, 20/60 to 20/100 in 2 patients, and 20/200 in 1
      patient. Traumatic maculopathy and epiretinal membrane formation were
      determinants of worse final visual acuity. CONCLUSIONS: Paintball pellet ocular
      injuries occur more frequently at home than at war game facilities. Advanced
      surgical techniques offer decreased ocular morbidity and improved visual acuity.
      Decreasing visual morbidity from paintball pellets requires public education,
      proper product labeling, and packaging of eye protection with all paintball
      related products.

PMID- 11846249
TI  - Characteristics of centenarians admitted to a community teaching hospital.
AB  - BACKGROUND: The "oldest old" are the most rapidly growing segment of society, and
      clinicians will increasingly encounter this age group in this century. METHODS:
      To describe the characteristics of a special subgroup of the oldest old, the
      centenarians, we conducted a retrospective case series analysis of all patients
      100 years of age and above admitted to a large community teaching hospital.
      RESULTS: Thirty-nine patients with a mean age of 101.3 years were admitted a
      total of 57 times during the 5-year study period. The main reasons for admission
      were hip fracture, stroke, and urinary tract infection. Patients admitted from
      nursing facilities were taking more medications than community dwelling patients,
      and patients who were confused on admission were more likely to be readmitted.
      Only 2 patients died. CONCLUSIONS: Polypharmacy is common in centenarians,
      especially in institutionalized patients, and confusion may be a useful predictor
      of subsequent readmission. In-hospital mortality, however, is low in this
      population.

PMID- 11846250
TI  - Evaluation of state-provided postexposure prophylaxis against rabies in Florida.
AB  - BACKGROUND: One key component of human rabies prevention is the use of
      postexposure prophylaxis (PEP). No information is routinely available to evaluate
      the appropriateness of this intervention. METHODS: A survey queried county health
      departments regarding rabies PEP administered during July through September in
      1997 and in 1998. RESULTS: A total of 160 cases meeting the study criteria were
      characterized. Domestic animals accounted for most potential rabies exposures.
      Nearly a quarter of the reports indicated that PEP was not necessary. Health
      departments collected just over 25% of costs for antirabies biologics.
      CONCLUSIONS: Human rabies prevention systems can be enhanced by reducing the
      number of PEP events through improved recovery of biting animals. Inappropriate
      administration of PEP and cost can be reduced by establishing a system of after
      the-fact review of every episode of PEP with timely feedback to providers.

PMID- 11846251
TI  - Epidemiology of human immunodeficiency virus testing among patients with
      tuberculosis in North Carolina.
AB  - BACKGROUND: Human immunodeficiency virus (HIV) testing is recommended for all
      patients with tuberculosis (TB). METHODS: Surveillance data for all reported
      cases of TB in North Carolina from 1993 to 1999 were examined to assess HIV
      testing practices. RESULTS: Of 3,680 TB patients, 3,119 (85%) had HIV testing
      data reported. Of these, 604 (19%) were not offered HIV testing, 465 (18%)
      refused testing, 379 (15%) were HIV seropositive, 29 (0.8%) were tested but
      results were not reported, and 1 (0.03%) had an indeterminate result. Older
      patients were significantly less likely to be offered HIV testing and more likely
      to refuse testing. Males and African Americans were more likely to be offered and
      to accept testing. CONCLUSIONS: At least 34% of TB patients in North Carolina
      from 1993 to 1999 did not receive HIV testing. Patients in higher-risk groups
      were more likely to be tested, but even within the highest-risk groups, testing
      was not universal. Health care providers should offer HIV testing to all
      individuals with TB.

PMID- 11846252
TI  - Anesthetic care in developing countries: equipment and techniques.
AB  - Various organizations have been formed to provide short-term surgical services in
      developing countries. In these countries, the ability to provide effective
      anesthetic care requires the team to transport most of the equipment necessary to
      provide perioperative care for various surgical procedures. We review the basic
      supplies necessary to provide such care and discuss some of the issues related to
      the anesthesia machines, techniques, and monitoring in developing countries.
      Suggestions and options for preoperative assessment, intraoperative anesthetic
      care, and postoperative care, including pain management, are provided.

PMID- 11846253
TI  - Large, vascular cecal mass.
AB  - A 74-year-old woman had a recent weight loss and history of breast and cutaneous
      malignancy. Medical evaluation included colonoscopy, which showed a 4 x 3 cm,
      vascular-appearing mass in the cecum. It was blue-tinged, soft, and easily
      deformed by pressure. Endoscopic ultrasonography characterized the lesion as a
      fluid-filled submucosal mass. Because of the suspicion of neoplasm, the patient
      had exploratory laparotomy and right hemicolectomy. Histopathologic examination
      revealed a lymphangioma. We review the literature regarding diagnosis and
      management of colonic lymphangiomas and describe a distinctive case.

PMID- 11846254
TI  - Scrotal enlargement in boys with a history of scrotal trauma: two unusual
      findings.
AB  - The presentation of a boy with an acutely painful scrotum is often associated
      with a history of trauma. Two recent patients with a history of scrotal trauma
      and an enlarged hemiscrotum were found on surgical exploration to have unusual
      causes for the scrotal enlargement. In the first case, there was bleeding from
      omentum in an incarcerated inguinal hernia, and in the second, there was bleeding
      into a scrotal cystic lymphangioma. Fewer than 40 cases of scrotal lymphangioma
      have been reported.

PMID- 11846255
TI  - Resolution of dyshidrotic dermatitis of the hand after treatment with continuous
      positive airway pressure for obstructive sleep apnea.
AB  - Eczema of the palm and obstructive sleep apnea (OSA) are common disorders.
      Proinflammatory cytokines and cell adhesion molecules are elevated in both of
      these disorders. We describe an unusual patient with OSA who had recurrent free
      remission of dermatitis after treatment with continuous positive airway pressure.
      We speculate that the resolution of the patient's skin condition may reflect the
      effects of increased tissue oxygenation during sleep, reduced sleep
      fragmentation, and/or a reduction in sympathetic tone associated with successful
      sleep apnea treatment.

PMID- 11846256
TI  - Salvage of limb and function in necrotizing fasciitis of the hand: role of
      hyperbaric oxygen treatment and free muscle flap coverage.
AB  - We report a case of necrotizing fasciitis of the hand treated by urgent
      debridement followed by serial debridements, hyperbaric oxygen, and delayed free
      muscle flap coverage. After control of the infection, a major soft-tissue defect
      remained on the dorsum of the wrist and hand, exposing all extensor tendons. A
      rectus muscle free flap was used for wound coverage and salvage of the exposed
      tendons; the muscle flap was covered with a delayed skin graft. The patient
      regained satisfactory function with ability to extend all digits. This case
      emphasizes the importance of aggressive debridement and hyperbaric oxygen
      treatment and shows the valuable role of free muscle flap wound coverage for
      preservation of function in cases of necrotizing fasciitis of the hand.

PMID- 11846257
TI  - Hypercalcemia induced by parathyroid hormone-related peptide after treatment of
      carcinoma.
AB  - Squamous cell carcinoma of the head and neck is a rare cause of humoral
      hypercalcemia of malignancy. This paraneoplastic syndrome is usually one of the
      presenting symptoms of the disease. We report a case of squamous cell carcinoma
      of the oral cavity that presumably elaborated parathyroid hormone-related peptide
      (PTH-rP) and caused hypercalcemia only after radiotherapy and chemotherapy.

PMID- 11846258
TI  - Intragastric gallstone-induced bezoar: an unusual cause of acute gastric outlet
      obstruction.
AB  - Bezoars are an uncommon cause of acute gastric outlet obstruction. To our
      knowledge, this is the first report of a bezoar formed around a gallstone that
      migrated to the stomach via a cholecystogastric fistula. Our patient was a 42
      year-old African American woman with long-standing type 2 diabetes. We suspect
      that diabetic diathesis was the major factor responsible for producing the
      pathologic derangement of the gallbladder and stomach, which led to development
      of the bezoar and serious complications.

PMID- 11846260
TI  - Compartment syndrome of the leg after less than 4 hours of elevation on a
      fracture table.
AB  - Compartment syndrome of the leg is usually associated with significant trauma. It
      has also been associated with prolonged surgery in the hemilithotomy position.
      Fracture tables that are used for the internal fixation of proximal femur
      fractures under fluoroscopy place a patient in this position. This report
      chronicles two cases of intraoperative compartment syndrome of the leg that was
      elevated and contralateral to a subtrochanteric femoral fracture. In each case,
      the syndrome was found at the procedure's conclusion and was addressed with
      fasciotomies. One patient continued to have neurologic sequelae from the
      compartment syndrome 2 years later.

PMID- 11846259
TI  - Recurrent respiratory tract infections and dysphagia in a child with an aortic
      vascular ring.
AB  - Recurrent respiratory tract infections and dysphagia after the first years of
      life are rarely caused by vascular rings, and only a high index of clinical
      suspicion helps to avoid diagnostic delay and inappropriate treatment. Diagnostic
      workup in a 2-year-old girl with acute foreign body impaction into the esophagus
      and frequent respiratory tract infections revealed right descending aortic arch
      with ligamentum arteriosum as the cause of extrinsic esophageal-tracheal
      compression. Dividing the ligament gave release to the encircled esophagus and
      trachea. Relief of symptoms was achieved immediately after surgery.

PMID- 11846261
TI  - Medical management of Cronkhite-Canada syndrome.
AB  - We report the case of a patient with Cronkhite-Canada syndrome (CCS) successfully
      treated with combination medical therapy. This rare, noninherited
      gastrointestinal polyposis syndrome is associated with characteristic ectodermal
      abnormalities. The etiology and pathogenesis of CCS are not known. No medical
      therapy has been shown to be consistently effective, and the disease is usually
      fatal. The patient described herein was successfully treated with a novel
      combination regimen consisting of H1- and H2-receptor antagonists, cromolyn
      sodium, prednisone, and suppressive antibiotics. This regimen has resulted in
      sustained improvement in symptoms, and follow-up endoscopy has shown regression
      of the diffuse polyposis. Our patient's response to such therapy may provide
      insight into the optimal treatment for CCS.

PMID- 11846262
TI  - Acute paraparesis due to terbutaline sulfate.
AB  - A woman who was 30 weeks pregnant was given terbutaline sulfate to prevent
      premature labor contractions. Within several days, she had an acute paraparesis
      with myalgias and was unable to walk. Full neurologic investigation failed to
      show any obvious cause. Terbutaline therapy was discontinued, and in 48 hours she
      became asymptomatic. Terbutaline sulfate (Brethine) is a beta-adrenergic agonist
      that works on smooth muscle. Various theories about its effect on skeletal muscle
      have been published. The importance of this case report is to make physicians
      aware of the rare muscular side effects of terbutaline, and careful observation
      may obviate extensive and invasive testing.

PMID- 11846263
TI  - Clarifying the role of teaching in the academic mission.

PMID- 11846264
TI  - Laundry detergents as a source of heavy metals in Irish domestic wastewater.
AB  - Concentrations of Cd, Cu and Zn in 175 detergent samples representing twenty-one
      brands of washing powders were analysed. Mean concentrations of 3.03 (+/- 0.50)
      microg Cd/g, 2.61 (+/- 1.22) microg Cu/g and 15.23 (+/- 7.26) microg Zn/g were
      recorded. The concentration of cadmium was much lower than previously reported.
      The daily contribution of metals from laundry washing are in the order of 54.5
      microg Cd/ca/d, 47.0 microg Cu/ca/d and 274.1 microg Zn/ca/d. In Irish municipal
      wastewater the contribution from detergents of these metals are 31.9% for Cd,
      0.24% Cu and 0.30% for Zn. This has important implications for sewage sludge
      disposal.

PMID- 11846265
TI  - A multimedia fugacity river model of pentachlorophenol in South Drainage Canal,
      China.
AB  - An investigation of Pentachlorophenol (PCP) in South Drainage Canal and Haihe
      Estuary, Tianjin, China was carried out from 1998 to 1999. PCP was found in each
      sample of the surface microlayer, subsurface water, sediment and air. The waste
      drainage from a PCP-producing plant was the main pollution source of PCP to Haihe
      Estuary. The enrichment phenomenon of PCP in the surface microlayer was reported
      for the first time. The maximum enrichment factor was 4.11. A multimedia
      (including air, the surface microlayer, water and sediment) fugacity river model
      was established and successfully applied to fate data for pentachlorophenol in
      South Drainage Canal. The results showed that under steady state, 97.09% of the
      loaded PCP was removed by advective outflow into Bohai Bay and 2.46% was by the
      biodegradation in the water phase. The residue of PCP in South Drainage Canal
      mainly distributed (99.56%) in the water phase. The discharge rate of PCP from
      South Drainage Canal to Bohai Bay was 53.4 kg/h.

PMID- 11846266
TI  - Development of a method for extraction of methyl tert-butyl (MTBE) from soil
      samples.
AB  - Methyl tert-Butyl Ether (MTBE) is ubiquitous in both ground and surface waters in
      the United States, and it can also be found in many unsaturated soil systems.
      Until recently, MTBE was not thought to adsorb appreciably to soil solids. MTBE,
      however, will adsorb to some soil types, and additionally, can be found in both
      soil water and soil gas. Since sorbed MTBE can serve as a long term, low level,
      source to water systems, a practical method for quantifying soil concentrations
      is needed to fully understand the environmental impact of MTBE. In this paper, we
      examine the analytical parameters critical to MTBE extraction methods, including
      extraction solvent and gas chromatograph characteristics. As the result, we have
      discovered toluene to be an effective solvent (exhibiting adequate recovery and
      excellent separation from MTBE) using a GC/FID with Suppelcowax column.

PMID- 11846267
TI  - Biodegradation of polyvinyl alcohol by Phanerochaete chrysosporium after
      pretreatment with Fenton's reagent.
AB  - Polyvinyl alcohol (PVA) solutions (BP05 and BF17; 5.0%, wt v(-1)) were degraded
      by a combination of chemical (Fenton's reagent) and fungal (Phanerochaete
      chrysosporium) treatments. The overall degradations of BP05 and BF17 were 74.4
      and 72.8%, respectively, as determined by chemical oxygen demand (COD) analysis,
      and 63.7% and 57.7%, respectively, as determined by total organic carbon (TOC)
      analysis. Increased retention times and changes in the intensity of the PVA peaks
      on gel permeation chromatograms indicated that PVA molecules of greater molecular
      weights were degraded to lower molecular weights by both the chemical and fungal
      treatments. The predominant enzyme secreted by P. chrysosporium in medium
      containing 2% (wt v(-1)) ground cereal bran in 60 mM phosphate buffer (pH 6.0)
      was manganese peroxidase. Neither laccase nor lignin peroxidase activity was
      detected. Manganese peroxidase was probably involved in the biodegradation of the
      PVA solutions.

PMID- 11846268
TI  - Sorption of benzene and naphthol to organobentonites intercalated with short
      chain cationic surfactants.
AB  - This work studies the sorption of benzene and naphthol by bentonites exchanged
      with quaternary ammonium surfactants tetramethylammonium (TMA) ion,
      benzyltrimethylammonium (BTMA) ion, tetraethylammonium (TEA) ion, and
      benzyltriethylammonium (BTEA) ion to elucidate how exchanged short chain organic
      cations affect the mechanistic function of the modified bentonite. Local high
      charge density areas are found at interlamellar surfaces of bentonite and
      intercalated short chain organic cations aggregate preferentially at these sites
      to form organic carbon phase effective in nonionic organic compounds (NOC)
      uptake. Experimental results indicate that the amount of benzene uptake decreases
      as the size of intercalated organic cation increases from TMA to BTMA to TEA to
      BTEA, presumably due to the different structures of organic carbon phase formed
      in organobentonite. In addition, benzene sorption capacity of organobentonite
      modified with short chain organic cation is highly sensitive to the cation
      exchange capacities (CEC) of bentonite used.

PMID- 11846269
TI  - Photoelectrocatalytic oxidation of rhodamine B in aqueous solution using Ti/TiO2
      mesh photoelectrodes.
AB  - To further improve the photooxidation techniques for water and waste-water
      purification, a Ti/TiO2 mesh electrode, was successfully prepared by anodizing Ti
      mesh in 0.5M H2SO4 solution. The structural and surface morphology of the Ti/TiO2
      electrode was examined by Raman spectroscopy and scanning electronic microscopy
      (SEM) respectively. The examination results indicated that its structure and
      properties were affected by its growth rate in the anodization process, and
      anatase TiO2 was dominant in its composition. The photocatalytic (PC) oxidation
      and photoelectrocatalytic (PEC) oxidation of rhodamine B in aqueous solution
      using the Ti/TiO2 electrode were investigated and compared. The experimental
      results demonstrated that the PEC oxidation by applying an electrical bias
      between the Ti/TiO2 electrode and Pt electrode could significantly enhance the
      degradation rate of rhodamine B compared with the PC oxidation. It was found that
      the best performance of PEC oxidation was achieved by applying the electrical
      bias of 0.6 V. The mechanism of rhodamine B degradation in the PEC process was
      discussed by studying the changes of absorbance spectrum and proton nuclear
      magnetic resonance spectroscopy of rhodamine B during the PEC degradation. The
      experimental results illustrated that both de-ethylation and chromogen
      destruction of rhodamine B under UV-light irradiation in the PEC degradation took
      place simultaneously.

PMID- 11846270
TI  - Mobility of heavy metals originating from bombing of industrial sites.
AB  - Surface soil samples from the "NIS Jugopetrol" fuel storage sites has been
      studied. The aim of this work has been the detection of heavy and inorganic
      metals including As, Pb, Cd, Ni, Zn, Cr, and Cu in soils after bombing present
      due to outflow, burning or leaking of crude oil and oil products at five chosen
      locations: Belgrade-Cukarica, Smederevo, Nis, Bor and Prahovo. In order to get
      information of the future environmental and health risks, sampling was repeated
      after several months at the same locations. Certain locations present a threat on
      environment because of the possible transport of contaminants during higher water
      levels.

PMID- 11846271
TI  - Root zone temperature affects the phytoextraction of Ba, Cl, Sn, Pt, and Rb using
      potato plants (Solanum tuberosum L. var. Spunta) in the field.
AB  - Three consecutive years of field experiments were conducted to investigate how
      different root-zone temperatures, manipulated by using different mulches, affect
      the phytoextraction of Ba, Cl, Sn, Pt and Rb in different organs of potato plants
      (roots, tubers, stems and leaves). Four different plastic covers were used (T1:
      transparent polyethylene; T2: white polyethylene; T3: white and black coextruded
      polyethylene, and T4: black polyethylene), using uncovered plants as control
      (T0). The different treatments had a significant effect on mean root zone
      temperatures (T0 = 16 degrees C, T1 = 20 degrees C, T2 = 23 degrees C, T3 = 27
      degrees C and T4 = 30 degrees C) and induced a significantly different response
      in Ba, Cl, Sn, Pt and Rb concentration and accumulation. The T3 treatment gave
      rise to the greatest phytoextraction of Ba, Pt, Cl and Sn in the roots, leaflets
      and tubers. In terms of the relative distribution of the phytoaccumulated
      elements (as percentage of the total within the plant), Pt and Ba accumulated
      mainly in the roots whereas Rb, Sn and Cl accumulated primarily in tubers,
      establishing a close relationship between the biomass development of each organ
      and phytoaccumulation capacity of metals in response to temperature in the root
      zone.

PMID- 11846272
TI  - Anaerobic granulation with methanol-cultured seed sludge.
AB  - A new biotechnology on sludge granulation in upflow anaerobic sludge blanket
      (UASB) system was developed in this study. Methanol-cultured sludge for UASB
      inoculation demonstrated a beneficial effect on the granulation process. This new
      biotechnology accelerated the formation of embryonic granules in a laboratory
      scale UASB reactor, and the granulation process reached its post-maturation stage
      in about 15-20 days ahead of the control reactor. There were no significant
      negative effects on COD removal and gas production due to this methanogen
      enriched seed sludge. Methanol-cultured seed sludge for UASB inoculation could be
      an effective method to reduce the time required for UASB system start-up.

PMID- 11846273
TI  - Pilot testing of dissolved air flotation (DAF) in a highly effective coagulation
      flocculation integrated (FRD) system.
AB  - Factors of pretreatment coagulation/flocculation units were studied using raw
      water of low temperature and low turbidity. Aluminum sulfate (AS) and selected
      polyaluminium chlorides (PACls) were all effective in the DAF process when used
      under favorable conditions of coagulant addition, coagulation, flocculation and
      flotation units. Compared with the AS coagulant, PACls, at lower dosage, could
      give the same effective performance even with shorter coagulation/flocculation
      time or lower recycle ratio during the treatment of cold water. This is
      attributed to the higher-charged polymeric Al species, and the lower hydrophilic
      and more compact flocculated flocs of PACl coagulant. Based on results of pilot
      experiments, the goal of FRD system can be achieved by combining a DAF
      heterocoagulation reactor with PACl coagulant (F), an efficient flocculation
      reactor (R), as well as an economical auto-dosing system (D).

PMID- 11846274
TI  - Microscopic characterization of oil droplets removed by flocs after coagulation
      of oil-water emulsions.
AB  - The objectives of this study were to investigate floc-droplet interactions during
      coagulation of oil-water emulsions and understand mechanisms of removal for
      selected hydrocarbons from aqueous solutions by analysis of microscopic images of
      the flocs formed after coagulation. Image analysis techniques were used to
      examine and statistically evaluate surface and structural characteristics of the
      flocs and oil droplets attached on the flocs. The coagulation experiments were
      conducted using standard jar test procedure to identify the optimum conditions
      for removal of decane, styrene, toluene and m-xylene from surface water samples.
      Removal effectiveness of the hydrocarbons was determined by gas chromatography
      analyses of the water samples before and after coagulation. The size distribution
      of the droplets which were attached on the flocs showed a significantly skewed
      pattern towards the smaller diameter droplets indicating that there is a
      characteristic droplet size range for attachment of droplets on the forming
      flocs. Percent removal of hydrocarbons increased as a function of log K(ow) of
      the contaminants used in the study. The image analysis techniques used for the
      examination of flocs provided information on specific floc properties as well as
      insight on removal mechanisms of droplets from emulsions.

PMID- 11846275
TI  - Kinetics of heavy metal ions removal by use of natural zeolite.
AB  - Kinetics of the uptake of cadmium, lead, copper, nickel and zinc ions from single
      ion solutions and from their mixture by zeolitic rock has been studied. Removal
      of ions obeyed the kinetic equation for adsorption. Corresponding adsorption
      constants and distribution coefficients were determined for each metal ion uptake
      from single ion solution or mixture. An attempt was made to explain zeolite
      selectivity to different metal ions and the influence of water hardness on the
      uptake in terms of metal ionic radii and enthalpy of hydration. It was found that
      lead ions were strongly immobilized by the zeolite investigated, both from single
      ion and mixed solutions, as well as from soft and hard water.

PMID- 11846277
TI  - Use of coagulant and zeolite to enhance the biological treatment efficiency of
      high ammonia leachate.
AB  - Most landfill leachates in Korea, herein defined as the contaminated liquid
      resulting from the percolation of water through a landfill, are high in ammonium
      nitrogen, which inhibits biological treatment processes and deteriorates rivers.
      A laboratory experiment investigated the effect of pre-removal of ammonium
      nitrogen using zeolite on the efficiency of organic treatment of the following
      activated-sludge process. Ferric chloride was initially used as a coagulant for
      solids removal. A clinoptilolite and mordenite rich rock from the Guryongpo area,
      the Yeongil Basalt, in Korea, reduced the ammonia nitrogen concentrations of
      leachate from 1300-1500 to 110-130 mg/l in a 24h batch operation. Three activated
      sludge reactors were operated to compare treatment efficiency under different
      influent conditions. In reactor 1, leachate having high concentration of chemical
      oxygen demands (COD) and suspended solids (SS) was directly fed to the reactor
      without pretreatment. The supernatant, after the coagulation process that remove
      some suspended solids and COD, was fed to reactor 2. As the use of coagulation
      process alone is not effective to remove ammonium nitrogen, supernatant treated
      by both coagulation focusing on the removal of COD and the zeolite concentrating
      on the removal of ammonium nitrogen was fed to reactor 3. As the result of
      experiment, greater efficiency in lowering the chemical oxygen demand (83%,
      influent COD; 1800-3000 mg/l, effluent COD; 300-500 mg/l) was achieved in reactor
      3. Meanwhile, 63% (influent COD; 4000-5000 mg/l, effluent COD; 1470-1840 mg/l)
      and 66% (influent COD; 2400-3300 mg/l, effluent COD; 820-1100 mg/l) removal
      efficiency of COD were achieved in reactors 1 and 2, respectively. Thus, ammonia
      pre-removal by zeolite remarkably improved the lowering of chemical oxygen demand
      and the solids separation in the activated sludge process.

PMID- 11846276
TI  - Factor optimization for phenol removal using activated carbon immobilized with
      Pseudomonas putida.
AB  - Removal efficiency of phenol from aqueous solutions was measured using a
      suspended culture of Pseudomonas putida (ATCC 3180) or the activated carbon on
      which the microorganisms were immobilized. Experiments were performed as a
      function of pH (7-9), temperature (30-36 degrees C), and concentrations of
      glucose (0.5-0.7 g/l) and ammonium sulfate (0.5-0.7 g/l). The Box-Behnken design
      was applied in a second-degree quadratic, polynomial regression model to identify
      the significant effects and the interactions among the above four factors. Based
      on response curve method the conditions for maximizing phenol removal (initially
      0.2 g/l) were recognized as pH 7, temperature 30 degrees C, glucose 0.6 g/l, and
      ammonium sulfate 0.6 g/l. The inhibition effect of carbon and nitrogen sources
      beyond a concentration of 0.6 g/l on phenol removal was obvious.

PMID- 11846278
TI  - Pathways and kinetics of redistribution of cobalt among solid-phase fractions in
      arid-zone soils under saturated regime.
AB  - An adequate supply of Co in pasture is important to the health of grazing
      animals. Bio-availability of Co in soils is largely depended upon its
      distribution among solid-phase fractions. Distribution of cobalt in six arid-zone
      soils and its redistribution among the solid-phase fractions during long-term
      saturated paste incubation were studied. Cobalt was fractionated by a selective
      sequential dissolution procedure into six empirically defined fractions.
      Concentrations of total Co and Mn or Fe, and Co and Mn fractionation pattern were
      strongly correlated in the soils. During saturated incubation, Co in soils was
      redistributed mainly from the Mn oxide bound, and to some extent, Fe oxide bound
      and organic matter bound fractions into the carbonate bound fraction. During
      saturated incubation, significant correlations were found between concentrations
      of Co and Mn in the Mn oxide bound, Fe oxide bound and carbonate bound fractions.
      Also, significant correlations between concentrations of Co and Fe in the Fe
      oxide bound fraction were present. However, a negative correlation between
      concentrations of Co and Fe in the Mn oxide bound fraction was observed. The
      rates of redistribution of Co between these solid-phase components were initially
      high: major changes occurred in the first 3 days in the sandy soil and the first
      18 days in the loessial soil. Afterwards, the rates of change slowed but changes
      in redistribution continued during the rest of the study period of one year.

PMID- 11846279
TI  - Filtration treatment of dairy processing wastewater.
AB  - The effectiveness of various filtration agents in the primary treatment of dairy
      processing wastewater was investigated in laboratory-scale studies. The
      filtration agents used were: zeolite, crushed coral, charcoal, sand and crushed
      coral and sand and glass beads. The effectiveness of the filtration media was
      determined by testing parameters such as chemical oxygen demand (COD), total
      solids (TS) and total suspended solids (TSS) before and after filtration of
      wastewater. Percent reduction of the different parameters as a result of
      filtration was calculated. Sand combined with crushed coral or glass beads was
      found to be the most effective filtering medium with an average reduction of 99%
      in TSS, 93% in COD and 51% in TS. Charcoal filtration resulted in an average 85%
      reduction in TSS, 83% reduction in COD and 46% reduction in TS. Filtration using
      crushed coral resulted in an average 83% reduction in TSS, 78% reduction in COD
      and 39% reduction in TS. Zeolite was the least effective of the four media; it
      resulted in an average reduction of 78% in TSS, 76% in COD and 30% in TS. The
      differences among mean values of COD, TSS and TS after the different treatments
      were analyzed statistically using analysis of variance (ANOVA). When differences
      among means were found to be statistically significant (p < 0.0001), each mean
      value was compared with every other mean value using Duncan's multiple range test
      and least significant difference (LSD) test. Comparison of the mean values
      indicated the following: No significant difference between means of zeolite and
      crushed coral treatment. Mean values of COD, TSS, and TS of charcoal treatment
      were significantly different from the other treatments. Sand combined with
      crushed coral or glass beads was the most effective filtration agent and the
      means were significantly different from the means of the other treatments.

PMID- 11846280
TI  - Leachability of radionuclides from cement-solidified waste form produced at
      Korean nuclear power plant.
AB  - The leach test of radionuclide in cement-solidified waste form was performed.
      After leach test, compressive strength of waste form was measured. Cement
      solidified waste form produced at Korean nuclear power plant, Kori (PWR) was
      chosen for the leach test. Specimens were cored out from a full-scale waste form
      (2001 drum size). The leach test procedure used for this study was ANSI/ANS 16.1
      procedure. The leach ability indexes for cesium and cobalt isotopes were
      determined. Semi-infinite model was used for analysis of the controlling
      mechanism in the release of isotopes. Release mechanism of cesium was dominated
      by diffusion but release of cobalt behaved somewhat differently from the
      diffusion controlled release. Averaged leachability indexes were 8.6 for cesium
      and 11.4 for cobalt. Compressive strength after leach/ immersion test was 7.34
      MPa for the sample immersed in simulated seawater and 8.34MPa for the sample
      immersed in deionized water.

PMID- 11846281
TI  - Tetrachloroethylene (TCE) removal during anaerobic granulation in an upflow
      anaerobic sludge blanket (UASB) reactor.
AB  - The anaerobic biotransformation of TCE was investigated during the granulation
      process by reducing the HRT and increasing the chemical oxygen demand (COD) and
      TCE loadings in a 21 laboratory-scale upflow anaerobic sludge blanket (UASB)
      reactor. Anaerobic unacclimated sludge and glucose were used as seed and primary
      substrate, respectively. Initial granules were developed after 1.5 months of
      start-up, which grew at an accelerated pace for 7 months and then became fully
      grown. The effect of operational parameters such as influent TCE concentrations,
      COD and TCE loading, food to microorganism (F/M) ratio and specific methanogenic
      activity (SMA) were also considered during granulation. The granular sludge
      cultivated had a maximum diameter of 2.5 mm and SMA of 1.32 gCOD (gTSS day)(-1)
      while 94% COD and 90% TCE removal efficiencies were achieved when the reactor was
      operating at loading rates as high as 160 mg TCE (1 day)(-1) and 14 gCOD (1 day)(
      1), respectively after 230 days of continuos operation. This corresponds to HRT
      of 0.28 day and F/M ratio of 0.60 gCOD (gTSS day)(-1). Kinetic coefficients of k
      (maximum specific substrate utilization rate), Ks (half velocity coefficient), Y
      (growth yield coefficient) and b (decay coefficient) were determined to be 2.38
      mgCOD (mgTSS day)(-1), 108 mgCOD 1(-1), 0.17 mgTSS (mgCOD)(-1) and 0.015 day(-1),
      respectively during TCE biotransformation based on glucose-COD during
      granulation.

PMID- 11846282
TI  - Assessing sanitary landfill stabilization using winter and summer waste streams
      in simulated landfill cells.
AB  - This study was undertaken to provide a better understanding and to further define
      the stabilization processes involved in a typical municipal landfill
      representative of the city of Calgary, Canada, area. The objectives of this study
      were: (1) to characterize the composition of the solid waste constituents
      entering the landfill site, (2) to assess the relative decomposition of various
      waste components in the simulated test cells, (3) to parametize selected chemical
      and physical changes occurring during the stabilization process and (4) to
      determine water absorptive capacity of the different waste constituents. The
      results of the long term landfill stabilization using simulated landfill cell
      systems filled with winter and summer waste streams, respectively, have
      illustrated the potential changes that may occur with time with such systems.
      Based on the results, it can be inferred that the seasonal variation in waste
      composition deposited in a landfill will likely effect the rate of decomposition
      and settlement, chemical and physical characteristics of the leachate, moisture
      sorbing capacity of the site as well as variation in seasonal contaminants.
      Assuming that the results from the simulated landfills used during this study can
      be extrapolated to larger-scale landfill operations, it seems that summer waste
      streams pose a higher pollution threat to the environment than winter waste
      streams. The several trends observed in this study and the conclusions reported
      herein would have wide applications in landfill management.

PMID- 11846283
TI  - Variation of toxicity during the ozonation of monochlorophenolic solutions.
AB  - This study investigates the variation of toxicity during ozonation of 2
      chlorophenol (2-CP), 3-chlorophenol (3-CP) and 4-chlorophenol (4-CP) in neutral
      condition. Acute toxicity of pure chlorophenols (CPs) and their ozonated
      intermediates was evaluated by Microtox assay. The results revealed that the
      intermediates of oxidized CPs induced new toxicity during the early stage of
      ozonation, and the ozonated 2-CP showed higher degree of toxicity increase than 3
      CP and 4-CP. The maximum toxicity normally occurred before the maximum color
      intensity was monitored, while ozone dosage applied was within 1 mg of ozone per
      mg of initial CPs. This increasing toxicity was mainly contributed from ozonated
      intermediates. Formation of chlorocatechols, chloromuconic acids and
      hydroxylated/chlorinated dimeric compounds were detected in ozonation of CPs.
      These chlorinated by-products may cause greater toxicity than the parent
      chlorophenols. The required ozone dosage to detoxify the CPs solution into a
      complete non-toxic condition follows the order: 4-CP > 3-CP > 2-CP.

PMID- 11846284
TI  - Effect of operational conditions on membrane permeability in a coagulation
      microfiltration process for water purification.
AB  - A coagulation-microfiltration combination process was used in treatment of
      simulative surface water. The effects of operational conditions such as
      filtration time, ceasing time and aeration intensity on the membrane permeability
      and organic removals were investigated. Experiment results showed that the
      membrane permeability could be improved through changing the operational
      conditions. Decreasing the filtration time or increasing the ratio of filtration
      time/ceasing time was favorable to enhance the membrane permeability. As the
      aeration intensity increased, the membrane permeability was also enlarged to some
      extent, but was not improved obviously anymore when the aeration intensity was
      over the critical value of around 4m3h(-1). Different wash methods to remove
      membrane fouling were attempted. The results suggested that coagulation in the
      process mainly led to change of the deposit cake-caused membrane fouling, which
      could be physically removed by surface wash. Organic removals, in terms of OC and
      UV254, apparently varied with the operational conditions. An inverse relationship
      between organic removals and membrane permeability was found. Lower membrane
      permeability led to higher OC and UV254 removals.

PMID- 11846285
TI  - Some polycyclic aromatic hydrocarbons in vegetables from northern China.
AB  - Nine important vegetables were collected from northern Chinese wholesale markets
      and analyzed for polycyclic aromatic hydrocarbon (PAH) contents. Anthracene,
      flupranthene, benzo(a)anthracene and benzo(a)pyrene were determined. The contents
      of the four PAH congeners were at the same level with the mean concentrations
      6.46, 4.05, 3.33, 4.51 microg kg(-1) for fresh weight for anthracene,
      flupranthene, benzo(a)anthracene and benzo(a)pyrene, respectively. However, leafy
      and stem vegetables had higher PAH content than root and fruit vegetables. Peels
      of the root and fruit vegetables had higher PAH concentrations than their cores.
      Human exposure to PAHs by consumption of these vegetables is estimated, by using
      typical northern Chinese intake rates, although the study was not designed to be
      statistically representative for the China as a whole.

PMID- 11846286
TI  - Helping patients with vision impairment adhere to a medication regime.

PMID- 11846287
TI  - Engaging black older adults and caregivers in urban communities in health
      research.
AB  - The under-representation of the Black population in research may lead to poor
      health outcomes for them and a decreased capacity to generalize results to Black
      populations. This article describes ways in which sensitivity to cultural
      distinctions of Black older adults and their current or future caregivers can
      enhance their recruitment and retention in research. Cultural mores play an
      important role in the shaping of one's perceptions, definitions, responses to
      disease, and participation in health regimens. Similarly, one's cultural
      orientation plays a role in how a person is effectively recruited and retained in
      resear Wenger's translation process model uses cultural meaning to inform
      research decisions. This model was used in a recent study of Black older adults
      and their caregivers and will be described in this article. Effectively engaging
      Black individuals in health research is essential for improving their health.

PMID- 11846288
TI  - Chronic pain in the older patient: management strategies. 2.
AB  - This is the second of a two-part series, which highlights issues and strategies
      related to pain assessment in older adults and current problems of pain
      management in older adults and analgesic regimens pertinent to this population.
      The complexities of assessing pain in older adults and assessment techniques for
      accomplishing a careful evaluation of pain were presented in the first part of
      this series, which was published in the January issue of the Journal of
      Gerontological Nursing (Vol. 28, No. 1). This article addresses issues and
      strategies related to management of pain, particularly analgesic use, in this
      challenging population.

PMID- 11846289
TI  - In assessment, all scores are not created equal.

PMID- 11846290
TI  - Residents' autonomy: nursing home personnel's perceptions.
AB  - While delivering quality care, nursing home personnel may unintentionally
      adversely affect residents' sense of personal autonomy. Faced with the challenge
      of respecting resident autonomy and simultaneously adhering to nursing home
      standards, nursing home staff often experience a frustrating ethical conflict.
      This study examines the effects of sets of independent variables on six autonomy
      dimensions to examine nursing home personnel's perceptions of how care was
      provided in their facility. For each of six case studies, respondents were asked
      the following question: "If Mr. or Mrs. X were at your facility, what would have
      been decided?" Responses were recorded along a continuum that indicated whether
      the resident would be allowed to make his or her own decisions or whether the
      nursing home staff would decide for the resident. Findings indicated staff
      members' education and race had the greatest effect on their perceptions of
      personal autonomy. Somewhat surprisingly, staffing levels, turnover rates, and
      restraint usage did not affect their views of autonomy. Additional research is
      recommended to more completely examine the complex dimensions of autonomy and to
      identify what changes nursing home staff and administrators could implement to
      improve residents' quality of life.

PMID- 11846291
TI  - Evidence-based practice for gerontological nursing.

PMID- 11846292
TI  - Change among aging adults.

PMID- 11846293
TI  - Evidence-based protocol: identification, referral, and support of older adults
      with genetic conditions.

PMID- 11846294
TI  - Transfusion therapy: a coming-of-age treatment for patients with sickle cell
      disease.

PMID- 11846295
TI  - Limited property rights in umbilical cord blood for transplantation and research.

PMID- 11846296
TI  - Clinical implications of mutations of neutrophil elastase in congenital and
      cyclic neutropenia.

PMID- 11846297
TI  - Reflections on events surrounding the time of diagnosis in pediatric oncology.

PMID- 11846298
TI  - This work we do: reflections from a pediatric hematology/oncology memorial
      service.

PMID- 11846299
TI  - Rhabdomyosarcoma and undifferentiated sarcoma in the first two decades of life: a
      selective review of intergroup rhabdomyosarcoma study group experience and
      rationale for Intergroup Rhabdomyosarcoma Study V.
AB  - PURPOSE: To review the importance of prognostic factors in developing new
      protocols for children with rhabdomyosarcoma (RMS). PATIENTS AND METHODS: Four
      studies conducted by the Intergroup Rhabdomyosarcoma Study (IRS) Group from 1972
      through 1991. RESULTS: Favorable prognostic factors are: (1) undetectable distant
      metastases at diagnosis; (2) primary sites in the orbit and nonparameningeal
      head/neck and genitourinary nonbladder/prostate regions; (3) grossly complete
      surgical removal of localized tumor at the time of diagnosis; (4)
      embryonal/botryoid histology; (5) tumor size < or = 5 cm; and (6) age younger
      than 10 years at diagnosis. The IRS-V protocols are risk-based and refine therapy
      by reducing exposure to cyclophosphamide and radiation therapy (XRT) in patients
      at low risk while adding new, active agents such as topotecan or irinotecan to
      the standard therapy of vincristine, actinomycin D, and cyclophosphamide (VAC)
      plus XRT for patients with unfavorable histology or advanced disease. Collection
      of biologic specimens from patients with newly diagnosed disease continues to
      identify other factors that may distinguish patients with favorable features from
      those who need more intensive therapy. A new protocol that takes into account
      their previous treatment is needed for patients with recurrent disease. This
      program (being planned) does not include bone marrow/stem cell reconstitution
      because this strategy has thus far failed to improve survival rates of patients
      with metastases at diagnosis. CONCLUSION: Better understanding of biologic
      differences and new, active agents are needed to improve outcome of patients with
      unfavorable features at presentation.

PMID- 11846300
TI  - Molecular confirmation of Ewing sarcoma.
AB  - OBJECTIVE: To analyze retrospectively results of reverse transcription polymerase
      chain reaction (RT-PCR) testing and demographic information in patients with
      known or suspected Ewing sarcoma/primitive neuroectodermal tumor family of tumors
      referred to the National Cancer Institute and to describe factors influencing the
      determination of molecular marker status. PATIENTS AND METHODS: Tumor samples
      from 76 patients from February 1997 to December 1999 were analyzed. In all cases,
      the diagnosis of this family of tumors was confirmed by histopathologic review.
      RESULTS: In 58 patients, the presence of a translocation associated with this
      family of tumors was confirmed using RT-PCR. Specifically, there were 45 Ewing
      sarcoma (EWS)-FLI type 1 translocations, four EWS-FLI type 2 translocations, five
      EWS-ERG translocations, and four less common EWS-FLI variants. Of patients with a
      confirmed translocation, four were confirmed only after nested RT-PCR techniques
      were used. In five patients who initially underwent needle biopsy, the diagnosis
      was confirmed only after open biopsy or repeat needle biopsy was undertaken.
      Samples from 18 patients were translocation-negative. Of these, seven samples
      were deemed inadequate for RT-PCR testing as a result of inappropriate tissue
      handling or the presence of necrotic material. Five patients were found to have a
      different diagnosis after complete histopathologic and molecular
      characterization. Six samples remained, in which adequate tissue was obtained
      with no evidence of a characteristic translocation. CONCLUSIONS: In apparently
      translocation-negative samples, close attention should be given to the
      possibility of an alternative diagnosis, the potential need for nested RT-PCR,
      and the possibility of an inadequate sample. Strong consideration should be given
      to the use of open biopsy as opposed to needle biopsy to avoid the need for
      repeat biopsies and the potential for inaccurate assessment of molecular marker
      status.

PMID- 11846302
TI  - Histology-specific expression of a DNA repair protein in pediatric
      rhabdomyosarcomas.
AB  - PURPOSE: DNA repair enzymes have a critical role in cellular maintenance and
      survival. The enzyme apurinic/apyrimidinic endonuclease/redox factor 1
      (APE/ref1), a key protein in the base excision repair pathway, displays both
      repair and redox control. We examined the role of APE/ref1 in pediatric embryonal
      and alveolar rhabdomyosarcomas (ARMS). MATERIALS AND METHODS: Using an
      immunohistochemical method, fixed tissue from 31 newly diagnosed pediatric
      rhabdomyosarcomas were evaluated for expression of APE/ref1. Tissue was obtained
      from Indiana University and the Cooperative Human Tissue Network. RESULTS: We
      demonstrated high levels of expression within the localized and metastatic
      embryonal rhabdomyosarcomas. This contrasted with both localized and metastatic
      ARMS, which had low levels of APE/ref1 expression. This histology-specific
      difference proved to be significant (P = 0.003). Furthermore, the expression
      within all tumors examined was localized to the nucleus and did not differ
      between localized and metastatic tumors. CONCLUSIONS: We propose several
      hypotheses to explain this histology-specific expression of APE/ref1 in pediatric
      rhabdomyosarcomas. Because the majority of ARMS expressed either the PAX3/FKHR or
      PAX7/FKHR fusion transcript, the low level of expression may be related to the
      redox activity of APE/ref1. The low levels may also be related to the
      bioreductive activity of APE/ref 1.

PMID- 11846301
TI  - Ifosfamide and etoposide are superior to vincristine and melphalan for pediatric
      metastatic rhabdomyosarcoma when administered with irradiation and combination
      chemotherapy: a report from the Intergroup Rhabdomyosarcoma Study Group.
AB  - PURPOSE: This study was designed to estimate the partial and complete response
      rates (CR and PR) of two novel drug pairs (vincristine and melphalan vs.
      ifosfamide and etoposide) and to improve overall survival of previously untreated
      patients with metastatic rhabdomyosarcoma. PATIENTS AND METHODS: One hundred
      twenty-eight patients were randomly assigned to phase II window therapy
      consisting of vincristine and melphalan (VM-containing regimen) or ifosfamide and
      etoposide (IE-containing regimen). Brief window therapy (12 wks) was immediately
      followed-up by vincristine, dactinomycin, and cyclophosphamide (VAC),
      chemotherapy, surgery, and irradiation, with continuation of either VM or IE in
      patients with initial response. Major endpoints were initial CR and PR rates
      after the phase II window phase of therapy, failure-free survival (FFS), and
      survival. RESULTS: Patients who received the VM-containing regimen experienced
      significantly more anemia, neutropenia, thrombocytopenia, and had more
      cyclophosphamide dose reductions. The initial PR and CR rates were not
      significantly different for patients treated with either regimen (VM, 74%; IE,
      79%; P = 0.428). However, FFS and overall survival (OS) at 3 years were
      significantly better with the IE-containing regimen (FFS: 33% vs. 19%; P = 0.043;
      OS: 55% vs. 27%; P = 0.012). CONCLUSIONS: Although the VM-containing regimen
      produced a high response rate, inclusion of melphalan appeared to limit the
      cyclophosphamide dose that could be administered, and ultimately, this regimen
      was associated with a significantly worse outcome than was the IE-containing
      regimen. Also, the IE-containing regimen was associated with a gratifyingly high
      survival rate at 3 years (55%), which is significantly higher than has been
      observed on any previous Intergroup Rhabdomyosarcoma Study Group regimen for
      similar patients. We believe that this promising outcome indicates that this drug
      pair merits further randomized testing in metastatic rhabdomyosarcoma.

PMID- 11846303
TI  - Epstein-Barr virus-associated Kikuchi disease in two children.
AB  - The authors describe two children with Kikuchi necrotizing lymphadenitis, the
      main manifestations of which were cervical lymphadenopathy, fatigue, and fever.
      The diagnosis was based on histopathologic findings after open biopsy. Results of
      serologic studies, immunoperoxidase staining for Epstein-Barr virus (EBV) latent
      membrane protein, in situ hybridization for Epstein-Barr encoded RNAs, and
      polymerase chain reaction amplification of EBV Epstein-Barr nuclear antigen-1
      (EBNA) DNA suggested that EBV was the causative agent in both patients. The
      disease was mild and subsided after complete surgical resection in one patient,
      with a follow-up of 1 year. In the other patient, a short course of
      corticosteroids led to complete clinical remission within 2 months, but the child
      still has biologic signs of persistent EBV infection. He experienced relapse with
      a large cervical mass and fever 28 months after the initial onset. Histologic
      findings were identical to those at initial presentation. Symptoms again resolved
      spontaneously within 2 weeks, but the follow-up was short (12 mos) and the
      child's EBNA antibodies are still absent. No evidence of immunodeficiency was
      found in either child. The cause of Kikuchi disease is unknown, but a viral or
      postviral hyperimmune reaction has been proposed. Malignant lymphoma and systemic
      lupus erythematosus are differential diagnoses. Early recognition of Kikuchi
      disease minimizes potentially harmful and unnecessary investigations and
      treatments. These findings add Kikuchi disease to the protean manifestations of
      chronic EBV infection.

PMID- 11846304
TI  - Factor V inhibitor in neonatal intracranial hemorrhage secondary to severe
      congenital factor V deficiency.
AB  - We report a newborn infant girl, born to consanguineous parents, with recurrent
      intracranial hemorrhage secondary to congenital factor V deficiency with factor V
      inhibitor. Repeated transfusions of fresh-frozen plasma (FFP) and platelet
      concentrates, administrations of immunosuppressive therapy (prednisolone and
      cyclophosphamide), and intravenous immunoglobulin failed to normalize the
      coagulation profiles. Exchange transfusion followed-up by administrations of
      activated prothrombin complex and transfusions of FFP and platelet concentrates
      caused a temporary normalization of coagulation profile, enabling an insertion of
      ventriculoperitoneal (VP) shunt for progressive hydrocephalus. The treatment was
      complicated by thrombosis of left brachial artery and ischemia of left middle
      finger. The child finally died from another episode of intracranial hemorrhage 10
      days after insertion of the VP shunt.

PMID- 11846305
TI  - Basal cell carcinoma originating from a nevus sebaceus on the scalp of a 7-year
      old boy.
AB  - Basal cell carcinoma (BCC) occurs rarely in children and is most often associated
      with an underlying condition that predisposes patients to the development of
      malignancy. There have been numerous reports of BCC developing after puberty in
      nevus sebaceus; however, such occurrences have rarely been described in children.
      We report a 7-year-old boy with BCC forming in a nevus sebaceus.

PMID- 11846306
TI  - Fatal warm autoimmune hemolytic anemia resulting from IgM autoagglutinins in an
      infant with severe combined immunodeficiency.
AB  - Autoimmune diseases are rare in patients with severe combined immunodeficiency
      (SCID). The authors describe an 11-month-old infant girl with SCID with fatal
      warm autoimmune hemolytic anemia (AIHA) resulting from IgM autoagglutinins.
      Serologic evaluation revealed IgM autoantibodies that caused in vitro
      hemagglutination at 37 degrees C. The patient had clinical evidence of ongoing
      hemolysis and agglutination despite aggressive treatment. She had three strokes
      and died 6 weeks after unsuccessful bone marrow transplantation. Autoimmune
      disease is an unexpected complication of SCID. The presence of warm reactive IgM
      autoagglutinins in AIHA confers a dismal prognosis.

PMID- 11846307
TI  - Foreign matter salpingitis 3 years after typhlitis.
AB  - This case suggests that typhlitis may cause delayed abdominal pathology. A
      history of this condition should be considered in the work-up of any patient with
      gastrointestinal or genitourinary pathology.

PMID- 11846308
TI  - Gastrointestinal stromal tumor in a patient with previous neuroblastoma.

PMID- 11846309
TI  - Interferon-alpha treatment as a possible cause of relapse in a child with
      precursor B acute lymphoblastic leukemia.

PMID- 11846310
TI  - Secondary thyroid carcinoma after treatment for clear cell carcinoma of the
      uterus: case report and review of the literature.

PMID- 11846311
TI  - Abdominal rhabdoid tumor presenting as fetal hydrops: a case report.

PMID- 11846312
TI  - Myelodysplastic syndrome, pyoderma gangrenosum, and Crohn disease.

PMID- 11846313
TI  - Interatrial conduction block and Wenckebach-type atrioventricular block.

PMID- 11846314
TI  - Removal of superfluous ICD leads.

PMID- 11846315
TI  - Kinetics of defibrillation shock-induced response: design implications for the
      optimal defibrillation waveform.
AB  - INTRODUCTION: Implantable cardioverter defibrillator (ICD) therapy is a well
      established therapy for treating patients at high risk for sudden cardiac death.
      Recently formulated virtual electrode polarization theory is a promising
      foundation for the theory of defibrillation. Yet, continuing optimization of
      defibrillation therapy is limited to primarily empirical methods due to
      difficulties in assessing kinetics of cellular response in whole heart models of
      defibrillation. The aim of this study was to evaluate the response of the
      myocardium in the context of virtual electrode polarization. METHODS AND RESULTS:
      We used a Langendorff-perfused rabbit heart model of ICD therapy and voltage
      sensitive fluorescent dye imaging in order to map kinetics of trans membrane
      potential during both mono- and biphasic shocks applied at various phases of the
      QT-interval. Cellular response was fitted to a single exponential function using
      the Levenberg-Marquardt method. Time constants (tau) were measured in 45 288
      optical records from 17 hearts. We found that cellular response depends upon both
      QT-phase of application, intensity, polarity, and phase of the biphasic waveform.
      Shocks of larger strengths produce a faster response. The tau of the first-phase
      negatively polarizing response was significantly larger compared with the
      positively polarizing response at intensities below 200 V, but smaller at 200 V
      and above. The tau of the second phase negatively polarizing response was always
      slower than the positively polarizing response, regardless of amplitude, and
      timing. Overall, tau ranged from 1.6 ms to 14.2 ms. CONCLUSIONS: The time
      constant of the membrane depends on the field, action potential phase and the
      shock polarity, but exceeds 1 msec. Therefore, we suggest using a slower shock
      leading edge, since the membrane cannot follow potentially damaging faster
      waveforms.

PMID- 11846316
TI  - High incidence of Pellethane 90A lead malfunction.
AB  - AIMS: The long-term performance of Pellethane 80A (P80A) endocardial pacing leads
      has previously been called into question. We report our experience with an
      endocardial pacemaker lead with silicone outer and Pellethane 2363-90A (P90)
      inner insulator. METHODS: Between November 1993 and March 1998, 129 P90A and 189
      non-P90A ventricular leads were implanted. Lead malfunction was defined as > or =
      25%) deviation in lead impedance or a two-fold reduction in sensing threshold
      during follow-up. Sensing and capture thresholds and lead impedance were assessed
      intraoperatively, immediately postoperatively, at 24 h and 6-12 weeks following
      implant and semiannually thereafter. Adequacy of lead positioning and lead-header
      interface were documented radiographically in each case. RESULTS: During 204
      patient years of follow-up, 10/129 (8%) Oscor RX P90A leads malfunctioned.
      Average time to malfunction was 14 +/- 11 months. During 166 patient years of
      follow-up, none of the 189 non-P90A ventricular leads met criteria for
      malfunction (P < 0.05). There was no difference in patient age, sex, and
      arrhythmia indication between groups. Sensing problems were overcome with
      pacemaker reprogramming. CONCLUSION: We conclude that Oscor RX passive fixation
      ventricular leads with external silicone and inner P90A insulation exhibit an 8%,
      insulation malfunction rate within 14 +/- 11 months of implant. This is
      significantly higher than non-P90A leads implanted with identical technique and
      follow-up regimen. More frequent follow up may be warranted in patients with P90A
      containing leads.

PMID- 11846317
TI  - PEA I and PEA II based implantable haemodynamic monitor: pre clinical studies in
      sheep.
AB  - AIMS: The aims of this study were first, to demonstrate that Peak Endocardial
      Acceleration during isovolumic systole (PEA I) is related to positive peak
      LVdP/dt, while Peak Endocardial Acceleration during isovolumic relaxation time
      (PEA II) is related to aortic diastolic pressure (ADP) and to negative peak
      LVdP/dt; and second, to test if the simultaneous recording of PEA I and PEA II
      offers a new chance to monitor indexes of LV systolic and diastolic function.
      METHODS: An implantable haemodynamic monitor, based on PEA I and PEA II
      measurements via a microaccelerometer sensor located in the tip of a pacing lead,
      screwed into the right ventricle, was tested in nine sheep at baseline and during
      acute haemodynamic interventions: nitrate (0.1 mg/ kg), metaraminol (0.15 mg/kg),
      dobutamine (5 microg/kg) infusion. ADP, positive and negative peak LVdP/dt were
      simultaneously recorded by an aortic and left ventricular Millar catheter.
      RESULTS: PEA I changes were significantly related to positive peak LVdP/dt
      changes during dobutamine induced inotropic changes (r = 0.83, P < 0.001). PEA II
      changes were significantly related to both ADP (r = 0.91, P < 0.001) and negative
      peak LVdP/dt changes (r = 0.92, P < 0.001) during nitrate induced hypotension and
      metaraminol induced hypertension. CONCLUSION: The simultaneous recording of PEA I
      and PEA II with an implantable system offers a new chance to monitor indexes of
      LV systolic and diastolic function.

PMID- 11846318
TI  - Pacemaker troubleshooting: improved efficacy using a new diagnostic digital
      Holter recording system.
AB  - Asymptomatic dysfunction of cardiac pacing systems is not uncommonly detected
      using long-term ambulatory monitoring techniques. We report two patients with
      atrial and ventricular sensing abnormalities noted only on Holter monitoring.
      Multiple empirical attempts at pacemaker reprogramming based on deductive
      analysis of the pacing anomaly were unsuccessful. Through the use of a new
      digital recording system that allowed collection of surface electrocardiographic
      data, intracardiac electrograms, and Marker Channel data a correct diagnosis was
      made (pacing lead insulation failure). This new recording system has the
      advantage of significantly improving diagnostic sensitivity and resulting in cost
      savings.

PMID- 11846319
TI  - Catheter ablation using very high frequency current: effects on the
      atrioventricular junction and ventricular myocardium in sheep.
AB  - BACKGROUND: Radiofrequency ablation is currently used in the treatment of various
      cardiac arrhythmias. However, this technique is limited by impedance rise,
      leading to coagulum formation and desiccation of tissue. We developed a new
      generator, providing very high frequency (27 MHz) current, which is in the
      intermediate range between radiofrequency and microwave energy. The aim of this
      study was to evaluate the results for catheter ablation of the atrioventricular
      junction and characteristics of the lesions obtained at ventricular sites.
      METHODS AND RESULTS: The generator was coupled to a specially designed 7-French
      coaxial catheter. The study included experiments performed on 10 sheep (Wt. 31-
      42 kg). In seven sheep, the catheter was introduced into the femoral vein and
      advanced across the tricuspid annulus to record the largest possible His
      electrogram. VHF current was applied for 25 s, with increasing energies. The
      energy needed to obtain complete atrioventricular (AV) block ranged from 60 to
      100 Watts. Six animals were observed for 6 to 21 days. Complete AV block was
      found to be persistent. In those seven sheep in whom AV junction was ablated and
      in three additional sheep, the ablation catheter was positioned toward the right
      ventricular apex using the same approach and into the left ventricle via the
      femoral artery, and 20 to 90 Watts energy was delivered in order to assess the
      size of the induced lesions. Side effects included ventricular tachycardia
      degenerating into ventricular fibrillation in six cases, but the same effect was
      observed in this animal model with radiofrequency energy. No cardiac perforation
      was noted. No thrombus was observed at the catheter tip. The size of the lesion
      ranged from 3 to 45 mm in width and 1 to 15 mm in depth. CONCLUSIONS: Catheter
      ablation using VHF current is feasible and appears effective in producing stable
      AV block when applied at the AV junction and results in substantial myocardial
      lesions. Further studies are needed to define its clinical interest and side
      effects.

PMID- 11846320
TI  - Programmed ventricular stimulation: influence of early versus late introduction
      of a third extrastimulus, a randomized, prospective study.
AB  - OBJECTIVE: The aim of this prospective study was to analyze the yield of early vs
      late introduction of a third extra-stimulus during programmed ventricular
      stimulation. METHODS: Two randomized protocols of programmed ventricular
      stimulation were used in 94 consecutive patients with coronary artery disease who
      were studied because of non-sustained ventricular tachycardia (9.6%), sustained
      monomorphic ventricular tachycardia (46.8%), ventricular fibrillation (18.1) or
      syncope (25.5%). During protocol A, a third extrastimulus was introduced during a
      basic drive cycle length of 500 ms after completion of programmed ventricular
      stimulation with 1 and 2 extrastimuli during sinus rhythm and paced cycle lengths
      of 500, 430. 370 and 330 ms. During protocol B, the third extrastimulus was
      introduced early (after 1 and 2 extrastimuli during sinus rhythm and a paced
      cycle length of 500 ms). Both protocols began at the right ventricular apex. If
      sustained ventricular tachyarrhythmia had been induced, the same sequence of
      programmed ventricular stimulation was repeated at the right ventricular outflow
      tract. RESULTS: The overall incidence of induced arrhythmias did not differ
      between the two protocols. However, the use of the third extrastimulus (both
      protocols) increased the yield of ventricular fibrillation induction
      significantly (P < 0.04) compared with ventricular tachycardia induction.
      CONCLUSIONS: The introduction of the third extrastimulus should be considered
      only at the end of stimulation protocols (especially in those patients without
      previously documented sustained ventricular tachyarrhythmias) in order to prevent
      induction of polymorphic ventricular tachycardia or fibrillation.

PMID- 11846321
TI  - Brugada syndrome in a patient with accessory pathway.
AB  - Brugada syndrome in a patient with Wolff-Parkinson-White syndrome. We report a 32
      year-old man with orthodromic atrioventricular (AV) reciprocating tachycardia
      using a right posterior accessory pathway. However, his ECG showed ST segment
      elevation in leads V1 to V3. After successful radiofrequency ablation of his
      accessory pathway a cardioverter defibrillator was implanted.

PMID- 11846322
TI  - Bystander cavo-tricuspid isthmus activation during post-incisional intra-atrial
      reentrant tachycardia.
AB  - We describe a case of post-incisional atrial tachycardia resembling typical
      atrial flutter on the surface ECG. Typical atrial flutter reentry was ruled out
      by the results of activation and entrainment mapping. Nevertheless, overdrive
      pacing from the lateral edge of the cavo-tricuspid isthmus produced tachycardia
      entrainment with concealed fusion associated with post-pacing and stimulus-to-P
      wave onset intervals exactly matching the tachycardia cycle length duration and
      the electrogram-to-P wave onset interval, respectively. Therefore, that site was
      firstly severed by sequential radiofrequency pulses. However, a transformation of
      the tachycardia P wave morphology and endocardial activation sequence, not
      associated with tachycardia termination or cycle length modification occurred.
      After additional mapping manoeuvres, a relatively small reentrant circuit was
      identified in the low and mid aspect of the lateral right atrium with the
      critical isthmus located between the lower border of a cannulation atriotomy and
      the crista terminalis, close to the inferior vena cava orifice. A single
      radiofrequency pulse at that site terminated the tachycardia. Both the
      electrocardiographic pattern and the endocardial mapping data obtained in our
      case might be explained by a split of the reentrant wavefront into a secondary
      wavelet which freely propagated through the cavo-tricuspid isthmus without
      completing the peritricuspid loop. In conclusion, bystander cavo-tricuspid
      isthmus activation during atrial tachycardia may simulate a typical atrial
      flutter pattern on the surface ECG. Further studies should evaluate the
      prevalence of this propagation pattern in post-incisional atrial reentry and
      atypical atrial flutters, and identify its implications for ablation strategy.

PMID- 11846323
TI  - Wide complex tachycardia and congenital heart disease.
AB  - We present a patient with congenital heart disease and haemodynamically poorly
      tolerated wide QRS tachycardia. Differential diagnosis and therapy are discussed.
      After the patient underwent heart transplantation, and the substrates for ECG
      abnormalities and arrhythmias were demonstrated in the explanted heart.

PMID- 11846324
TI  - The Tromso study: registration of fractures, how good are self-reports, a
      computerized radiographic register and a discharge register?
AB  - In order to compare different methods of fracture registration, we sought all
      nonvertebral fractures suffered during 8 years (1988-95) among 21,441 persons
      invited to a survey in 1979/80. We registered a total of 54 hip fracture cases
      through three separate sources (self-report, computer linkage to the local
      radiographic archives, discharge register), whereas forearm fractures (a total of
      291 cases) were registered through two separate sources (self-report, computer
      linkage to the radiographic archives). The registration of fractures at other
      sites (a total of 1321 cases) were from one source (computer linkage to the local
      radiographic archives), and we have compared three ways of obtaining data from
      this single source (no ascertainment, ascertainment of records coded as fracture,
      ascertainment of all records). Ninety-three percent of all hip fractures and 97%
      of all wrist fractures in the entire study population were found by computer
      linkage to the radiographic archives, whereas the discharge register detected 87%
      of all the hip fractures. Computer linkage with ascertainment gave no
      overreporting of fractures. Among the 11,626 persons who answered a follow-up
      questionnaire in 1994/95, 97% (CI 84-100%) of all hip fractures and 72% (CI 66
      78%) of all wrist fractures were self-reported. We conclude that a computerized
      search of radiographic archives is a viable method of fracture registration.

PMID- 11846325
TI  - Changes in biochemical markers of bone turnover in women treated with raloxifene:
      influence of regression to the mean.
AB  - Measures with extreme magnitude are most likely to be the result of measurement
      variability. Repeated measurements genuinely lessen such variability, leading to
      a phenomenon known as regression to the mean (RTM), which may affect biochemical
      markers of bone turnover. We therefore studied four markers of bone turnover in
      the Multiple Outcomes of Raloxifene Evaluation (MORE) trial--serum procollagen
      type I C-propeptide (PICP), osteocalcin (OC), bone-specific alkaline phosphatase
      (BAP) and urinary type I collagen breakdown product (CTX)--among the 1704 women
      treated with raloxifene who had marker measurements and were at least 70%
      adherent, and among 915 control group patients. We examined the existence of RTM,
      and applied a method of adjustment for RTM of both baseline and follow-up
      results. We found that women who had the most extreme values tended to go in the
      opposite direction with the subsequent measurement, i.e., exhibited a pattern of
      RTM. For example, among women whose urinary CTX decreased at least 60% in the
      first 6 months, 61% had an increase in the next 6 months; and among those who had
      an increase in the first 6 months, 81% had a decrease in the next 6 months. We
      found a similar pattern for each of the four markers. When adjusting for RTM we
      obtained estimated true values of both baseline values and change in markers.
      These estimated true values were substantially different from the observed value
      when the latter was further from the mean. For example, for a 10% increase in
      urinary CTX in the first 6 months, after accounting for RTM we estimate that
      there was in fact a 3% decrease (80% confidence interval: -38% to 53%). We
      conclude that the few initial extreme marker responses observed in women treated
      with raloxifene represent RTM, and that one practical consequence is that
      patients with an increase in markers during the first 6 months should be
      continued on raloxifene therapy, because the values usually decrease later on.

PMID- 11846326
TI  - Association of a G2014A transition in exon 8 of the estrogen receptor-alpha gene
      with postmenopausal osteoporosis.
AB  - We report the association of a newly identified synonymous G2014A single
      nucleotide polymorphism (SNP) which does not alter the amino acid sequence in
      exon 8 of the estrogen receptor-alpha (ERalpha) gene with osteoporosis in Thai
      postmenopausal women. Subjects consisted of 228 postmenopausal women aged more
      than 55 years divided into two groups--with vertebral or femoral osteoporosis (n
      = 106) or without osteoporosis (n = 122)--according to bone mineral density (BMD)
      criteria. The exon 8 G2014A SNP, which is 6 nucleotides upstream from the end of
      the stop codon, was identified by PCR-RFLP. Data are expressed as the mean and
      95% CI. The allele frequency of the G2014A polymorphism was 26.4% in osteoporotic
      subjects and was significantly higher than that in non-osteoporotic women (15.2%)
      (p<0.05). By stepwise logistic regression analysis, it was found that the G2014A
      polymorphism was related to the presence of osteoporosis (odds ratio 2.7 per A
      allele, 95% CI 1.49-4.76) independently of body weight (odds ratio 0.93 per kg,
      95% CI 0.89-0.96) and years since menopause (odds ratio 1.12 per year, 95% CI
      1.08-1.19). In a multiple linear regression model, L2-L4 BMD of osteoporotic
      subjects was associated with body weight (p<0.05), endogenous estradiol levels
      (p<0.05) and the G2014A genotype (p<0.001), while it was related only to body
      weight (p<0.05) and estradiol levels in non-osteoporotic women (p<0.05). We
      conclude that a G2014A SNP in exon 8 of ERalpha is associated with the presence
      and severity of postmenopausal osteoporosis. Linkage disequilibrium between this
      polymorphism and the 3'-untranslated region of the ERalpha gene which may
      participate in the regulation of ERalpha gene expression remains to be
      determined.

PMID- 11846327
TI  - Raloxifene versus continuous combined estrogen/progestin therapy: densitometric
      and biochemical effects in healthy postmenopausal Taiwanese women.
AB  - We treated 116 healthy postmenopausal women (age 47-66 years, mean 57 years) in
      Taiwan with either raloxifene (RLX) 60 mg (n = 92) or 0.625 mg conjugated equine
      estrogen plus 5 mg medroxyprogesterone acetate (CCEP, n = 24) daily for 12 months
      in a randomized, double-masked, active-controlled fashion. The results showed
      that both regimens increased bone mineral density (BMD) at hip sites (means: RLX
      2.5-4.9%, CCEP 4.6-7.9%, all p<0.005 compared with baseline), and the difference
      between the two regimens was not significant. The spinal BMD increased
      significantly in both groups (1.4% with RLX and 6.0% with CCEP, both p<0.01), and
      more with CCEP (p<0.003). Osteocalcin levels and urinary type I collagen C
      telopeptide/creatinine ratios decreased significantly in both regimens, but the
      decreases were significantly larger with CCEP. Compared with baseline, both RLX
      and CCEP decreased the total cholesterol (median 4.9% and 8.6% respectively,
      p<0.001) and LDL-cholesterol (median 11% and 19% respectively, p<0.001), and
      increased HDL-cholesterol (median 8.6% and 10.7% respectively, p<0.01). Both
      regimens increased triglyceride levels (median 3.2% and 18.9% respectively, both
      p<0.05), although to a lesser extent with RLX than with CCEP (p<0.05). Only 3
      subjects (3.3%) reported vaginal bleeding in the RLX group, as compared with 31%
      (7/22) with CCEP (p<0.05). We conclude that in healthy, postmenopausal Taiwanese
      women, RLX 60 mg given daily has favorable results in BMD, bone turnover and
      serum lipids, although the dosage we used showed a potency less than that of
      conventional CCEP.

PMID- 11846328
TI  - Longitudinal evaluation of vitamin D status in healthy subjects from southern
      Italy: seasonal and gender differences.
AB  - Vitamin D status is currently considered among the relevant determinants of
      skeletal integrity. Since vitamin D levels present seasonal variations, we
      longitudinally studied young healthy men and women in order to investigate the
      related physiologic modifications of both calcium homeostasis and bone
      remodeling. Thirty-two men (mean age 39.4 +/- 7.8 years) and 58 premenopausal
      women (aged 36.9 +/- 6.4 years) from southern Italy were studied. In all subjects
      the following parameters were measured both in winter and in summer: serum
      calcium, phosphorus, creatinine, total alkaline phosphatase activity, 25
      hydroxyvitamin D (25OHD), parathyroid hormone (PTH), osteocalcin (BGP), together
      with urinary calcium (Ca/Cr), total pyridinoline (Pyr/Cr) and deoxypyridinoline
      (d-Pyr/Cr), corrected for creatinine excretion. In both sexes 25OHD levels were
      significantly higher in summer, while PTH values were lower, than in winter. The
      prevalence of hypovitaminosis D, defined by concentrations of 25OHD lower than 30
      nmol/l, was 17.8% in winter and 2.2% in summer in the whole sample, while it was
      27.8% and 3.4%, respectively, among female subjects. Indeed male subjects did not
      display hypovitaminosis D, having throughout the year significantly higher
      calcium and 25OHD levels together with lower PTH values, than the women.
      Moreover, alkaline phosphatase total activity was more elevated in men both in
      winter and in summer. In women, during winter, bone remodeling markers levels
      were higher while urinary calcium levels were lower than in summer. In the whole
      sample serum 25OHD correlated positively with serum calcium and inversely with
      PTH. The seasonal percentage variations in PTH were inversely correlated with
      those of Ca/Cr. Our results show a relatively high prevalence of subclinical
      vitamin D deficiency among young healthy women from southern Italy. Significant
      gender-specific differences have been demonstrated in both calcium homeostasis
      and skeletal remodeling indexes; the seasonal fluctuations in the vitamin D-PTH
      axis are accompanied by cyclical variations of bone turnover rate, which were
      more pronounced in women.

PMID- 11846329
TI  - Relationship between disease activity and serum levels of vitamin D metabolites
      and parathyroid hormone in ankylosing spondylitis.
AB  - Vertebral fractures due to osteoporosis are a common but frequently unrecognized
      complication of ankylosing spondylitis (AS) and various factors may contribute to
      the development of osteoporosis in AS. It is known that inflammatory activity in
      rheumatic disease (i.e., proinflammatory cytokines) itself plays a possible role
      in the pathophysiology of bone loss. 1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) seems
      to be another possible candidate for mediatory function in regulating both the
      inflammatory process and bone turnover. The aim of this study was to evaluate the
      relation between disease activity, bone turnover and calciotropic hormones. In 70
      patients with established AS and an age- and sex-matched control group, the
      relation between disease activity (erythrocyte sedimentation rate, C-reactive
      protein, Bath Ankylosing Spondylitis Disease Activity Index), and serum levels of
      vitamin D metabolites, parathyroid hormone (PTH), bone alkaline phosphatase (bAP)
      and urinary pyridinium cross-links were determined. Serum levels of 1,25(OH)2D3
      (p<0.01) and PTH (p<0.01) were negatively correlated with disease activity, the
      excretion of urinary pyridinium crosslinks showed a positive correlation with
      disease activity (p<0.01), and 1,25(OH)2D3 and PTH were positively correlated
      with bAP (p<0.01). These results indicate that high disease activity in AS is
      associated with an alteration in vitamin D metabolism and increased bone
      resorption. Furthermore, the decreased levels of 1,25(OH)2D3 may contribute to a
      negative calcium balance and inhibition of bone formation. Our results suggest
      further research is necessary to determine whether low levels of 1,25(OH)2D3 as
      an endogenous immune modulator suppressing activated T cells and cell
      proliferation may accelerate the inflammation process in AS.

PMID- 11846330
TI  - Relation of BsmI vitamin D receptor gene polymorphism to bone mineral density and
      occurrence of osteoporosis in postmenopausal Chinese women in Taiwan.
AB  - Osteoporosis is a common disorder with a strong genetic component. Our aim was to
      evaluate the correlation of the vitamin D receptor gene intron 8 BsmI
      polymorphism with bone mineral density (BMD) and their relationship to
      osteoporosis. We determined the vitamin D receptor gene intron 8 BsmI
      polymorphfsm using polymerase chain reaction-based restriction analysis in 171
      postmenopausal Chinese women in Taiwan. The polymorphism was detected using the
      restriction enzyme BsmI, where the B allele indicated absence of the cuttable
      site and the b allele its presence. BMD of the lumbar spine and proximal femur
      were measured using dual-energy X-ray absorptiometry. The allelic frequencies for
      postmenopausal Chinese women in Taiwan were 12.3% for B and 87.7% for b in BsmI
      restriction fragment length polymorphisms. The prevalence of each genotype in the
      study population was: 6.4% BB, 11.7% Bb and 81.9% bb. The three genotypic groups
      differed significantly in BMD at the lumbar spine and the femoral neck. These
      differences corresponded to significant gene-dose effects at the lumbar spine and
      femoral neck (p<0.001 for both sites). The relative risk for the development of
      osteoporosis was about 2-3 times as great as that predicted by the differences
      between genotypes in BMD, and remained significant even after adjustment for age,
      height and weight. The vitamin D receptor gene intron 8 BsmI polymorphism is
      associated with reduced BMD and predisposes women to osteoporosis.

PMID- 11846331
TI  - Impact of hip and vertebral fractures on quality-adjusted life years.
AB  - The objective of the study was to estimate the impact of hip and vertebral
      fractures on quality of life in postmenopausal women using a preference-based
      health measure that is appropriate for economic evaluations and to investigate
      correlates of health outcome. Interviews to assess health-related quality of
      life, which also documented other health conditions and characteristics, were
      undertaken in women age 50 years and older without osteoporotic fractures
      compared with women with hip and/or vertebral fracture(s). Health status was
      characterized by self-reported physical limitations and the mental and physical
      component summary scores of the SF-36. Quality-adjusted life years (QALYs), which
      reflect each individual's assessment of her overall health utility, were
      estimated with time tradeoff values. Regression methods were used to examine QALY
      correlates (e.g. time since fracture) for each fracture group and to estimate
      differences in QALYs between fracture and non-fracture subjects after accounting
      for other patient characteristics. Among 382 women ages 50-96 years, fracture
      subjects were significantly older, less likely to use hormone replacement therapy
      and more likely to report physical limitations than non-fracture subjects. On the
      QALY scale, where 1 represents perfect health and 0 represents death, mean QALY
      values were 0.82 (95% CI: 0.76, 0.87) among 114 women with one or more vertebral
      fractures and 0.63 (95% CI: 0.52, 0.74) among 67 with hip fracture compared with
      0.91 (95% CI: 0.88, 0.94) among 201 women without fracture. No significant
      correlates of QALYs were identified among women with vertebral fracture alone.
      Among hip fracture subjects, time since hip fracture and presence of a vertebral
      fracture were significant correlates of QALYs. In multiple regression analyses,
      estimated QALY differences (fracture minus non-fracture subjects) ranged from 
      0.05 to -0.55 and were equivalent to losses of 20-58 days, 23-65 days and 115-202
      days per year for vertebral fracture (p = 0.001), hip fracture (p = 0.009) and
      hip plus vertebral fracture (p<0.001) subjects, respectively, depending on age.
      Thus to adequately assess the cost-effectiveness of osteoporosis treatment, the
      negative impact of vertebral fractures on QALYs, even among women who have
      survived a hip fracture, must be considered.

PMID- 11846332
TI  - Fall characteristics, functional mobility and bone mineral density as risk
      factors of hip fracture in the community-dwelling ambulatory elderly.
AB  - Hip fracture is the most serious consequence of osteoporosis, frequently
      occurring in the elderly; however, no research has been performed to identify the
      fall characteristics, functional mobility and bone mineral density (BMD)
      concurrently as risk factors. We investigated the risk factors of hip fractures
      using a multifactorial approach for a further preventive strategy. This age- and
      sex-matched case-control study was conducted in a community-based general
      hospital. A total of 252 consecutive community-dwelling ambulatory elderly, aged
      between 65 and 85 years, were studied: 127 patients (faller with hip fracture)
      and 125 controls (faller without hip fracture). Body mass index (BMI),
      predisposing medical conditions, fall characteristics, functional mobility and
      BMD of the hip were evaluated by direct interview and clinical examination. In
      the final model of multivariate regression analysis, risk factors for hip
      fracture were direct hip impact (adjusted odds ratio (OR), 4.9; 95% confidence
      interval (CI), 2.7-8.8), previous stroke (adjusted OR, 2.9; 95% CI, 1.3-6.3),
      sideways fall (adjusted OR, 2.5; 95% CI, 1.6-3.9), functional mobility (a
      decrease of 1 SD; adjusted OR, 2.0; 95% CI, 1.1-3.5), BMI (a decrease of 1 SD;
      adjusted OR, 1.8; 95% CI, 1.1-2.8) and femoral neck BMD (a decrease of 1 SD;
      adjusted OR, 1.7; 95% CI, 1.0-2.8). The effect of risk factors remained the same
      in different analysis sets, and adding or removing femoral neck BMD did not
      change other risk factors, though BMD was significantly correlated with
      functional mobility and BMI. Importantly, both sideways fall and direct hip
      impact are independent predictors of hip fracture. From these results, we suggest
      a preventive strategy of hip fracture in the elderly: besides the maintenance of
      BMD, keeping an appropriate body weight and maintaining a physically active
      lifestyle might be crucial.

PMID- 11846333
TI  - Ten year probabilities of osteoporotic fractures according to BMD and diagnostic
      thresholds.
AB  - The objectives of the present study were to estimate 10 year probabilities of
      osteoporotic fractures in men and women according to age and bone mineral density
      (BMD) at the femoral neck. Risks were computed from the incidence of a first hip,
      distal forearm, proximal humerus and symptomatic vertebral fracture from patient
      records in Malmo, Sweden and future mortality rates for each year of age from
      Poisson models using the Swedish patient register and statistical year book.
      Fracture probability was computed using the Swedish population and cut-off values
      for T-scores based on the NHANES III female population. We assumed that the risk
      of fracture increased with decreasing BMD as assessed by meta-analysis in
      independent studies. The 10-year probability of any fracture was determined from
      the proportion of individuals fracture-free from the age of 45 years. With the
      exception of forearm fractures in men, 10 year probabilities increased with age
      and T-score. In the case of hip and spine fractures, fracture probabilities for
      any age with low BMD were similar between men and women. The effect of age on
      risk independently of BMD suggests that intervention thresholds should not be at
      a fixed T-score but vary according to absolute probabilities. Intervention
      thresholds based on hip BMD T-scores are similar between sexes.

PMID- 11846334
TI  - Vitamin K administration to elderly patients with osteoporosis induces no
      hemostatic activation, even in those with suspected vitamin K deficiency.
AB  - The administration of menaquinone-4 (MK-4), one of subclasses of vitamin K2,
      significantly reduces bone loss in postmenopausal osteoporotic women. However,
      concerns have been raised about whether vitamin K administration alters the
      hemostatic balance by inducing a thrombotic tendency. We investigated were
      whether the administration of vitamin K in the form of MK-4 induced a thrombotic
      tendency in 29 elderly patients with osteoporosis (5 men, 24 women; age range
      78.7+/-5.1 years). Patients were administered 45 mg/day (three times a day, 30
      min after each meal) of MK-4 for 12 weeks. Blood samples were obtained from the
      patients at 0, 4 and 12 weeks after the start of MK-4 administration. A number of
      hemostatic parameters remained stable under the markedly increased plasma levels
      of MK-4. However, in patients with suspected vitamin K deficiency, whose plasma
      levels of vitamin K or factor VII were low, vitamin-K-dependent clotting factors
      such as factor VII and prothrombin were gradually increased after administration
      of MK-4. No changes in the sensitive molecular markers such as TAT and F1+2,
      which reflect the amount of thrombin generated in the blood stream, were
      observed, even in those patients with suspected vitamin K deficiency. These
      results indicate that MK-4 can be administered safely, with regard to maintaining
      the hemostatic balance, to osteoporotic patients receiving no anticoagulant
      therapy.

PMID- 11846335
TI  - Advances with bisphosphonates in the treatment of metabolic bone diseases.
      Introduction.

PMID- 11846336
TI  - Bisphosphonates for the treatment of postmenopausal osteoporosis: clinical
      studies of etidronate and alendronate.
AB  - Several large, prospective, controlled trials have demonstrated that
      bisphosphonates such as etidronate and alendronate are effective and generally
      safe for the treatment of postmenopausal osteoporosis. The results of these
      trials show a remarkable degree of consistency and indicate that long-term
      bisphosphonate therapy significantly increases BMD of the spine and of other
      skeletal sites, reduces the risk of vertebral and nonvertebral fractures, and
      generally is safe and well tolerated by patients. Data supporting the use of
      risedronate for the treatment of postmenopausal osteoporosis are presented in an
      accompanying article.

PMID- 11846337
TI  - Risedronate for the prevention and treatment of postmenopausal osteoporosis:
      results from recent clinical trials.
AB  - Postmenopausal osteoporosis is a widespread condition that affects the physical
      and emotional well-being of millions of women worldwide. In the clinical trials
      reviewed here, antiresorptive therapy using the bisphosphonate, risedronate,
      significantly reduced the incidence of vertebral and nonvertebral fractures,
      increased BMD in both early and late menopausal women, and decreased biochemical
      measures of bone resorption. The safety profile of risedronate appears comparable
      to placebo. These findings demonstrate that risedronate is effective and well
      tolerated for the prevention and treatment of postmenopausal osteoporosis.

PMID- 11846338
TI  - Bisphosphonates for the prevention and treatment of corticosteroid-induced
      osteoporosis.
AB  - Corticosteroid-induced osteoporosis is a common occurrence among several
      different patient populations, including individuals undergoing therapy for
      rheumatoid arthritis, temporal arteritis, polymyalgia rheumatica, chronic lung
      disease, asthma and organ transplantation. The clinical trial data reviewed here
      demonstrate that bisphosphonate therapy can reverse, at least in part,
      established corticosteroid-induced osteoporosis, increase BMD, and prevent the
      development of new fractures. The consistency of results, with varying treatment
      regimens and in slightly different patient populations, provides strong support
      for the generalizability of these findings and for the use of bisphosphonates in
      corticosteroid-induced osteoporosis. These results are consistent with the
      findings from a recent meta-analysis, which reviewed data from 13 controlled
      clinical trials of bisphosphonate use in corticosteroid-induced osteoporosis. In
      that analysis, 1 year of bisphosphonate therapy produced a significant increase
      in BMD at the lumbar spine (average difference in BMD between treated and control
      groups of 4.0%) and femoral neck (average BMD difference of 2.1% between treated
      and control patients). Bisphosphonate therapy, therefore, appears to be an
      effective, well-tolerated means of reducing the risk of bone fractures among
      patients treated with corticosteroids.

PMID- 11846339
TI  - Neuroticism and the Irrational Health Belief Scale.

PMID- 11846340
TI  - Cardiovascular reactivity during social and nonsocial stressors: do children's
      personal goals and expressive skills matter?
AB  - The relationships between social competence and cardiovascular reactivity were
      evaluated in 180 children (ages 8-17; 52% female; 53% Caucasian). Participants
      performed a social task (Social Competence Interview [SCI]) and 2 nonsocial tasks
      while reactivity measures were obtained. Social competence was coded from SCI
      audiotapes. Among adolescents, higher scores on the Acceptance-Affiliation
      subscale were associated with increased heart rate (HR) and blood pressures and
      with decreased HR variability during the SCI. Among boys, greater Acceptance
      Affiliation scores were associated with increased vascular reactivity during the
      SCI. During the nonsocial tasks, higher Self-Defensiveness and Expressiveness
      scores were associated with increased cardiac output and stroke volume among
      African American children. Personal strivings and expressive skills do matter for
      understanding cardiovascular responses in children.

PMID- 11846341
TI  - From heart attacks to melanoma: do common sense models of somatization influence
      symptom interpretation for female victims?
AB  - Common sense models regarding gender and stress influenced how laypeople
      responded to information about symptoms in 3 experiments. In Study 1, medical
      intervention was perceived to be less important for female targets reporting
      chest pain and stressful events than for male targets experiencing identical
      symptoms and stressors. In addition, chest pain was less likely to be attributed
      to cardiac causes for female targets. This gender-based stress-discounting effect
      was replicated for symptoms of gallstones and melanoma in Study 2, where
      participants again were less likely to recommend medical care for female than for
      male targets. Recognition memory for information about a somatizing target was
      tested in Study 3; results suggested that laypeople hold stereotypes associating
      somatization with female gender. The authors' findings provide insight into the
      naive theories that shape symptom interpretation and self-referral behavior.

PMID- 11846342
TI  - Correlates of colorectal cancer screening compliance and stage of adoption among
      siblings of individuals with early onset colorectal cancer.
AB  - Concepts from the health belief, transtheoretical, and dual process models were
      used to examine how siblings of individuals diagnosed with colorectal cancer
      (CRC) before age 56 made decisions about CRC screening. Siblings (N = 504) were
      assessed for CRC screening practices and intentions, pros, cons, processes-of
      change, perceived risk of CRC, perceived severity of CRC, preventability of CRC,
      cancer-related distress, and sibling relationship closeness. Physician and family
      recommendation and knowledge were also assessed. Fifty-seven percent of
      participants (n = 287) were compliant with CRC screening. Logistic regression
      indicated that perceived pros and cons, perceived risk, commitment to screening,
      health care avoidance, and sibling closeness were associated with screening
      compliance. Physician and family recommendation were also strong correlates. A
      similar set of factors was associated with stage of adoption of CRC screening.

PMID- 11846343
TI  - Hostility and facial expression in young men and women: is social regulation more
      important than negative affect?
AB  - Behavioral differences may clarify the link between hostility and health. This
      study examined facial expression. Seventy-two low- and high-hostile
      undergraduates underwent the Type A Structured Interview (SI) and a test of
      social anxiety. Facial behavior was measured with the Facial Action Coding
      System. Low-hostile participants displayed non-Duchenne smiles more frequently
      than high-hostile participants during the SI. There were no group differences in
      the expression of disgust. The results identify differences in the nonverbal
      behavior of hostile people. Restricted use of non-Duchenne smiles may reflect
      limited use of appeasement, contributing to uncomfortable interpersonal relations
      and limited social support. The findings are consistent with a behavioral ecology
      perspective and suggest that social regulation may be as important as negative
      affect in determining the consequences of hostility.

PMID- 11846344
TI  - Facilitating autonomous motivation for smoking cessation.
AB  - Physicians used either an autonomy-supportive or a controlling interpersonal
      style to counsel smokers based on National Cancer Institute guidelines. Physician
      autonomy support was rated from audiotapes, and patients' perceived competence
      and autonomous motivation for quitting were self-reported on questionnaires.
      Validated point prevalences for 6, 12, and 30 months and for continuous cessation
      were examined. The intervention did not have a direct effect on quit rates;
      however, structural equation modeling supported the self-determination process
      model of smoking cessation. The model indicated that the autonomy-supportive
      intervention was rated as more autonomy supportive, that rated autonomy support
      predicted autonomous motivation, and that autonomous motivation predicted
      cessation at all points in time. Perceived competence contributed independent
      variance to cessation only at 6 months.

PMID- 11846345
TI  - Testing mediating variables in a school-based nutrition intervention program.
AB  - This study identified mediators of a school-based nutrition intervention for 4th
      graders and their parents. Nine variables were tested for satisfying 4
      conclusions necessary to establish mediation of intervention effects on changes
      in fruit and vegetable consumption (FVC) in 4th graders (N = 1,676). FVC was
      measured in children by the use of 24-hr dietary recalls. Mediators were assessed
      by the use of questionnaires completed by children and parents. All 4 conclusions
      were met for positive outcome expectancies. Knowledge, self-efficacy, and parent
      consumption satisfied the first 3 conclusions for mediation but the mediating
      effects were not statistically significant (Conclusion 4). Future mediational
      analyses and the creation of a national database of mediators are crucial for
      increasing strength and efficiency of school-based nutrition programs.

PMID- 11846346
TI  - Personality, personal model beliefs, and self-care in adolescents and young
      adults with Type 1 diabetes.
AB  - This study compared 3 models of association between personality, personal model
      beliefs, and self-care in a cross-sectional design. These models were as follows:
      (a) Emotional stability determines self-care indirectly through personal model
      beliefs, and conscientiousness is a direct predictor of self-care; (b) emotional
      stability determines self-care indirectly through personal model beliefs, and
      conscientiousness moderates the association between beliefs and self-care; (c)
      both emotional stability and conscientiousness determine self-care indirectly
      through personal model beliefs. Participants (N = 358, aged 12-30 years) with
      Type 1 diabetes completed measures of personality, personal model beliefs, and
      self-care. Structural equation modeling indicated that Model C was the best fit
      to the data.

PMID- 11846347
TI  - Tests of the mediational role of preparatory safer sexual behavior in the context
      of the theory of planned behavior.
AB  - The present research details 2 empirical tests within the context of the theory
      of planned behavior (I. Ajzen & T. Madden, 1986) of the assumption that
      preparatory behaviors (e.g., discussing safer sex, obtaining condoms) play a
      mediational role in the relation between psychological variables (e.g., attitudes
      toward safer sex, social norms about safer sex) and condom use. The assumption of
      the mediational role of preparatory behaviors is examined in sexually experienced
      samples from 2 different populations: inner-city high school students (N = 226)
      and college students (N = 160). The results suggest that the mediational role of
      preparatory behaviors is a highly significant one. Results indicate no gender
      differences with regard to the main mediational hypotheses. The methodological,
      theoretical, and practical implications and importance of these findings are
      discussed.

PMID- 11846348
TI  - The role of personality in exposure and reactivity to interpersonal stress in
      relation to arthritis disease activity and negative affect in women.
AB  - The role of personality in the stress process was examined in older women with
      rheumatoid arthritis (RA) and osteoarthritis (OA) and in healthy controls (HCs).
      Reactivity was examined in relation to arthritis disease activity and negative
      affect. Interpersonal sensitivity and neuroticism were measured in
      questionnaires, and interpersonal stress, negative affect, and disease activity
      were assessed weekly for 12 weeks. Interpersonal sensitivity was defined as an
      excessive sensitivity to the behavior and feelings of others. Regarding exposure,
      neuroticism was related to interpersonal stress for all groups. Regarding
      reactivity, interpersonal sensitivity interacted with interpersonal stress to
      predicted elevations in negative affect in all groups and elevations in disease
      activity in the arthritis groups. There were no significant differences in the
      effects.

PMID- 11846349
TI  - Abuse, health locus of control, and perceived health among HIV-positive women.
AB  - This study of 230 predominantly poor Hispanic and African American women aged 25
      to 61 years living with HIV/AIDS in New York City revealed high levels of both
      sexual (39%) and physical (44%) trauma before the age of 16. Both types of early
      trauma were correlated with later trauma, and all forms of trauma were
      significantly associated with current perceived health. In multivariate analyses
      controlling for relevant covariates, the Powerful Others and Internal Control
      subscales of the Multidimensional Health Locus of Control Scales (K. A. Wallston,
      B. S. Wallston, & R. DeVellis, 1978) acted as independent predictors of perceived
      health rather than (as hypothesized) mediators of the association between trauma
      and perceived health. Findings underscore the importance of addressing trauma and
      perceptions of control over one's physical health in the provision of health
      services to HIV-positive women.

PMID- 11846350
TI  - Distraction intervention for preschoolers undergoing intramuscular injections and
      subcutaneous port access.
AB  - This study evaluated a distraction intervention designed to reduce the distress
      of preschool children undergoing repeated chemotherapy injections. Twenty-nine
      children aged 2-5 years were randomly assigned either to distraction by a
      developmentally appropriate electronic toy or to a wait-list control. Children
      who received the distraction intervention demonstrated lower overt behavioral
      distress and were rated by parents and nurses as less anxious than children in
      the control condition. The improvements were maintained over the 8-week
      intervention. The results suggest that a developmentally appropriate,
      multisensory, variable-distracting activity that requires active cognitive
      processing and active motor responses may be a viable cost-effective alternative
      to more time-intensive parent-training programs for preschool-age children.

PMID- 11846351
TI  - Diagnosis and treatment of posttransplantation lymphoproliferative disease after
      hematopoietic stem cell transplantation.
AB  - Uncontrolled expansion of donor-derived Epstein-Barr virus (EBV)-infected B cells
      has become a significant problem in recipients of allogeneic hematopoietic stem
      cell transplantations. Major risk factors for the early development of
      posttransplantation lymphoproliferative disease include the use of unrelated or
      HLA-mismatched related donors, selective T-cell depletion of donor marrow, and
      the use of antithymocyte globulin or monoclonal anti-T-cell antibodies for the
      prophylaxis and treatment of acute graft-versus-host disease. Over the past few
      years, the administration of in vitro-generated EBV-specific cytotoxic T cells or
      anti-B-cell monoclonal antibodies has provided effective options for the
      prophylaxis or treatment of posttransplantation lymphoproliferative disease.
      Advances in quantitative polymerase chain reaction-based assays allow both the
      precise measurement of EBV load in peripheral blood samples and the
      identification of high-risk patients for early initiation of therapy. A major
      remaining challenge is to assess the significance of an elevated EBV load
      posttransplantation and to determine the indications for preemptive treatment.

PMID- 11846352
TI  - NK inhibitory-receptor blockade for purging of leukemia: effects on hematopoietic
      reconstitution.
AB  - One of the obstacles of BMT that limits its efficacy is failure to eradicate the
      original tumor. The incidence of tumor relapse is particularly high after
      autologous BMT. Natural killer (NK) cells comprise various subsets that can
      express inhibitory receptors for MHC class I determinants. We have recently
      demonstrated that blockade of NK-cell inhibitory receptors can augment antitumor
      effects in vitro and in vivo. However, breakdown of tolerance and autoreactivity
      may occur as a result of the inhibition of NK-cell inactivation to self MHC
      determinants. We have utilized F(ab')2 fragments of monoclonal antibody, 5E6,
      against Ly49C/I inhibitory receptors, which are expressed on 35% to 60% of NK
      cells in H2b strains of mice and are specific for H2Kb, to investigate the effect
      of inhibitory-receptor blockade on syngeneic bone marrow cell (BMC) and tumor
      cell growth. We show that treatment of interleukin 2-activated C57BL/6 (B6, H2b)
      SCID-mouse NK cells with 5E6 F(ab')2 fragments during 48-hour coculture resulted
      in autoreactivity against syngeneic BMCs as demonstrated by suppression of
      myeloid reconstitution on day 14 post-BMT. However, this suppressive effect was
      transient and normalized by day 21 post-BMT. In contrast, blockade of inhibitory
      receptors during 24-hour coculture had no adverse effects on myeloid
      reconstitution after BMT. Furthermore, under the same coculture conditions, NK
      cell-mediated purging of C1498 leukemia cells contaminating syngeneic BMCs was
      more effective with inhibitory-receptor blockade, leading to a significantly
      higher proportion of animals with long-term survival compared to the control
      recipients. These results demonstrate that short-term in vitro blockade of
      inhibitory receptors can augment antitumor activity without long-term inhibitory
      effects on BMCs and thus may be of potential use in the purging of contaminating
      tumor cells prior to autologous BMT.

PMID- 11846353
TI  - HLA-identical sibling peripheral blood stem cell transplantation in children and
      adolescents.
AB  - Allogeneic peripheral blood stem cell transplantation (PBSCT) was performed in
      children and adolescents for the treatment of malignant (n = 49) and nonmalignant
      hematological disease (n = 8). Granulocyte colony-stimulating factor (G-CSF)
      mobilized PBSCs were apheresed from 57 HLA-matched siblings aged 9 months to 24
      years (median, 8 years) without any serious adverse, effects. No abnormalities
      were found in these donors for a median follow-up of 25 months (range, 6-56
      months). Patients were conditioned with a TBI-containing regimen (n = 17) or a
      non-TBI regimen (n = 40). GVHD prophylaxis consisted of methotrexate (MTX) plus
      cyclosporine A (CSP) for 23 patients, CSP plus methylprednisolone (mPDN) for 22
      patients, MTX only for 7 patients, CSP only for 4 patients, and MTX plus CSP plus
      mPDN for 1 patient. Engraftment was prompt, with a median number of days to reach
      an absolute neutrophil count (ANC) above 0.5 x 10(9)/L of 13 days (range, 8-23
      days), with 1 graft failure. Acute GVHD (grades II-IV) occurred in 8 (16%) of 49
      evaluable patients, and chronic GVHD developed in 23 (64%) of 36 evaluable
      patients. Notably, two thirds of chronic GVHD was extensive. The Kaplan-Meier
      estimate of 3-year disease-free survival was 0% for refractory disease (n = 6),
      37.2% +/- 11.8% for high-risk malignancies (n = 25), 81.4% +/- 9.7% for standard
      risk malignancies (n = 18), and 100% for nonmalignant disease (n = 8). The
      estimated 100-day nonrelapse mortality rate was 9.9% +/- 4.2%. In conclusion,
      allogeneic PBSCT is feasible in a pediatric population. Although the grade of
      acute GVHD was set low, as in Japanese BMT studies, the incidence and severity of
      chronic GVHD appears to be relatively high. For nonmalignant disease, the
      question arises of whether the higher incidence and severity of chronic GVHD is a
      drawback of this procedure. For high-risk malignancies, whether or not a graft
      versus-leukemia effect prevents relapse needs to be clarified in future
      comparative studies with BMT.

PMID- 11846355
TI  - Evaluation of the risk of therapy-related MDS/AML after autologous stem cell
      transplantation.
AB  - A major complication of autologous stem cell transplantation (ASCT) is the
      development of therapy-related myelodysplastic syndromes (MDS) and acute
      myelogenous leukemia (AML). This complication likely results from previous
      exposure of the autologous stem cells to chemotherapy as well as to the high
      doses of chemotherapy and radiation therapy that are used as part of the
      conditioning regimen. A number of centers are reporting that, second to disease
      relapse, therapy-related MDS and AML are among the major causes of morbidity and
      mortality after ASCT. There is abundant evidence that therapy-related MDS and AML
      are clonal hemopathies that are consequence of an acquired somatic mutation that
      confers a proliferative and/or survival advantage to hematopoietic progenitors.
      However, no single mutation or gene rearrangement is sufficient for the
      development of therapy-related AML, and the identification of a singlegene
      rearrangement or point mutation may not necessarily be predictive of the
      development of therapy-related AML in the post-ASCT setting, a caveat that must
      be kept in mind when risk is assessed. There are at least 5 methods for assessing
      risk based on the presence of clonal abnormalities in hematopoietic cells,
      including standard cytogenetics, interphase fluorescence in situ hybridization,
      analysis for loss of heterozygosity, polymerase chain reaction for point
      mutations, and X-inactivation-based clonality assays. Each of these approaches
      has strengths and weaknesses that are discussed here in detail.

PMID- 11846354
TI  - A survey of diagnosis, management, and grading of chronic GVHD.
AB  - Chronic GVHD (cGVHD) is a potentially devastating late complication of allogeneic
      stem cell transplantation. To better understand current diagnostic and treatment
      practices regarding this complication, we mailed a self-administered survey to
      188 adult and pediatric transplantation programs. The survey collected data on
      experience with therapies for cGVHD and presented 6 vignettes to assess agreement
      about the diagnosis, clinical management, grading, and prognosis of patients with
      symptoms of cGVHD. Response rate to the survey was 51%. Of the respondents, 28%
      felt they had "great success" in treating patients with systemic corticosteroids,
      and 13% had similar success with cyclosporine or mycophenolate mofetil; less
      success and experience were reported with other agents. Respondents estimated an
      average 3-year, nonrelapse mortality of 16% (95% CI, 14%-19%) for patients
      assessed to have limited disease and 39% (95% CI, 36%-43%) for extensive disease.
      Analysis of responses to the 6 vignettes showed that agreement was greatest for
      supportive care issues, willingness to enroll patients in clinical trials, and
      use of systemic immunosuppression for symptomatic cGVHD. Less agreement was seen
      for diagnosis and management when cGVHD manifestations were atypical or less
      severe, the decision of whether to taper immunosuppression in the face of stable
      symptoms, and for assignment of mild, moderate, or severe cGVHD grades. Most
      respondents were willing to use systemic immunosuppression to treat symptoms that
      they believed to be caused by cGVHD, but differences of opinion about cGVHD
      diagnosis and disease activity resulted in significant practice variation. Low
      estimates of treatment success were noted and reflected an overall pessimism
      about the success of therapy for cGVHD. We conclude that studies defining
      appropriate diagnostic pathways, criteria for disease activity, and prognosis
      could help standardize management of cGVHD. There is an urgent need to develop
      and test new approaches to treat cGVHD.

PMID- 11846358
TI  - Accomplishment and commitment: the National Task Force on Hepatitis B
      Immunization, Focus on Asians and Pacific Islanders.

PMID- 11846359
TI  - Volunteerism alive and well among members: The National Task Force on Hepatitis B
      Immunization, Focus on Asians and Pacific Islanders. Spotlight on Alice Chan,
      R.N.

PMID- 11846360
TI  - The natural history of hepatitis B in Asian Americans.
AB  - PURPOSE: This article provides an overview of the natural history of hepatitis B
      virus (HBV) infection, its complications, treatment and impact on the Asian
      American population in the United States. A discussion of the impact that
      hepatitis B vaccination can have on reducing HBV infection and liver disease is
      also provided. METHODS: A review of current literature on the history, diagnosis,
      complications and treatment of HBV infection was conducted as well as a review of
      current hepatitis B vaccination efforts. PRINCIPAL FINDINGS: HBV infection is
      common in the Asian American population, with 1 in 10 Asian Americans affected.
      Perinatal and childhood transmission account for most of these chronic cases.
      Molecular genetic advances have allowed for advances in understanding of this
      disease in chronically infected individuals. Interferon therapy and/or Lamivudine
      are currently the main therapies. CONCLUSIONS: Even though considerable success
      has been shown with drug therapy, and numerous other agents are under
      investigation, the high morbidity and mortality from cirrhosis of the liver and
      hepatocellular carcinoma of those chronically infected with HBV, risk prevention
      and vaccination will have to be the main foci for future eradication. The
      combined efforts of public health, health practitioners, immunization and cancer
      control leaders and voluntary and advocacy organizations are necessary to achieve
      universal hepatitis B vaccination.

PMID- 11846361
TI  - The epidemiology of hepatitis B vaccination catch-up among AAPI children in the
      United States.
AB  - PURPOSE: The purpose of this paper is to report on progress in addressing a major
      health disparity. During the 1970s hepatitis B virus (HBV) infection rates in
      U.S. Asian American and Pacific Islander (AAPI) children were 20-30 times higher
      than among white children. These rates remained 17 times greater among AAPI
      children into the 1990s. Now, although almost 90% of AAPI children born after
      1993 receive hepatitis B vaccine (HepB) in time to prevent HBV infection, many
      born before 1993 do not. Among this group, household HBV transmission remains
      relatively high--0.5%-1% annually. METHODS: In the mid-1980s household HBV
      transmission was studied among AAPI communities and by 1999 HepB coverage
      surveys, demonstration projects, and interventions in schools, communities, and
      provider offices were conducted followed by ethnic-specific controlled trials and
      cost-benefit research. The goal was established to reach 90% coverage by 2004.
      PRINCIPAL FINDINGS: Since 1995, catch-up efforts raised HepB coverage among AAPI
      children born 1983-1993 from 10% to 60%. Now, AAPI children targeted for catch-up
      are 9-19 years of age. Currently, most students entering middle school have not
      received their HepB series, but recently enacted middle school entry requirements
      in 26 states and Washington D.C. ensure at least 60% of AAPI students receive
      HepB by 12 years of age. High school students are less likely to have received
      HepB--no high school entry regulations are present to ensure vaccination.
      CONCLUSIONS: Much progress has been made toward eliminating this health
      disparity. More progress can be made if more health departments in the largest
      cities conduct high school HepB interventions, starting in schools with the
      highest numbers of AAPI. In addition, physicians and nurses can remove existing
      barriers to vaccination services and implement effective tracking/reminder/recall
      procedures to ensure the AAPI teenagers in their practice receive HepB.

PMID- 11846362
TI  - The declining prevalence of hepatitis B virus infection among Asian and Pacific
      Islander children.
AB  - PURPOSE: This article provides a review of the literature on the decline of
      hepatitis B virus (HBV) infection in Asian and Pacific nations having universal
      hepatitis B immunization programs. METHODS: Papers on the epidemiology of HBV
      infection and hepatitis B immunization programs in Asian and Pacific nations were
      located by searching MEDLINE and libraries for publications in English, and by
      contacting hepatitis B experts. PRINCIPAL FINDINGS: High endemicity for HBV in
      Asian and Pacific nations was partly caused by a cycle of high infectiousness,
      perinatal transmission, and chronic infection from early ages. Higher prevalence
      of infection has been found in men, some families, communities, and ethnic
      groups, and in people with high risk behaviors and situations, such as attending
      day care, getting injections, or sharing personal items. Incidence of acquisition
      of infection is about 2%-5% per year. Prevalence of HBV infection was declining
      in some nations before commencing hepatitis B immunization programs, probably
      because of improvements in medical practices and living conditions. Twenty-seven
      of 34 Pacific and East and Southeast Asian nations have attained >70% hepatitis B
      vaccination coverage in infants, and twelve have documented reducing infection or
      liver cancer to fractions of their former rates. But the immunization programs
      may be causing natural selection of mutant hepatitis B viruses, necessitating
      study of the mutants, and modification of serological tests and vaccines.
      CONCLUSIONS: Practical implications for U.S. health professionals are: increasing
      HBV screening and hepatitis B vaccination of adolescents and adults from Asian
      and Pacific nations can prevent many infections and disease cases; most children
      coming from high coverage Asian and Pacific nations will be immune and few
      infected; we can learn much from these successful programs; and we should still
      make efforts to immunize Asian and Pacific children in the United States, and
      help Asian and Pacific nations which do not yet have highly successful hepatitis
      B immunization programs.

PMID- 11846363
TI  - Hepatitis B vaccination among Vietnamese-American children in a Boston community
      clinic.
AB  - PURPOSE: This manuscript describes one community health center s efforts to
      provide catch-up immunization for hepatitis B for Vietnamese Americans aged 7 to
      17. METHODS: A chart review of 151 Vietnamese-American children seen at the
      health center was conducted in Spring, 2001. Letters were sent to notify parents
      of their children's immunization status. One month later, the investigators
      attempted to contact the parents by phone. The interviews were done to conduct a
      survey about hepatitis B virus (HBV), and to encourage parents whose children
      needed further follow-up to do so. PRINCIPAL FINDINGS: Chart review revealed that
      2% (n=3) of the patients were chronically infected with HBV, and 28% (n=42) were
      known to be already immune due to prior exposure. Thirteen patients had either
      moved or were obtaining care elsewhere. Of those needing vaccination (n=93), 76
      (82%) completed the series of three vaccines. Of the remaining 17 patients
      needing further follow-up, 9 were vaccinated in the community clinic, for a 91%
      vaccination rate (85 of 93). For this survey, a 63% survey response rate was
      achieved among the patients' parents (55 of 88 eligible households). Of parents
      reporting that their children had a hepatitis B vaccination (HepB), study
      investigators were unable to confirm 25% by chart review. Although letters were
      sent regarding their children's HBV status, only 71% reported having heard of
      HBV, and 60% reported having heard of HepB vaccine. The children's receipt the
      HepB vaccine was not significantly associated with the parents' having heard of
      HBV or HepB vaccination, the parents' length of time in the United States, their
      health insurance status, or their level of education. CONCLUSIONS: These findings
      suggest that parents need more education about HBV, and that the information they
      provide about their children's vaccination status may not be reliable.

PMID- 11846364
TI  - A population-based hepatitis B vaccination coverage survey among Asian and
      Pacific Islander American students in Alachua County, Florida.
AB  - PURPOSE: The goal of this project was to evaluate the impact of the Florida
      mandatory hepatitis B vaccination law on the immunization status of Asian
      American and Pacific Islander (AAPI) students in Gainesville. METHODS: We (1)
      compared the differences of hepatitis B immunization rate between students in
      grades seven through nine and grades 10 through 12, (2) assessed knowledge of and
      attitudes towards hepatitis B vaccination of parents of AAPI students, and (3)
      promoted the importance of Hepatitis B vaccination among those who have not
      received the vaccination. PRINCIPAL FINDINGS: Two hundred and eighty-eight AAPIs
      were enrolled in grades seven through 12; 42 could not be contacted. Forty-seven
      percent of the parents (n = 116) consented to in-home interviews and gave
      permission to verify the immunization status. An additional 65 parents gave
      permission to verify the immunization status, but did not consent to be
      interviewed. CONCLUSIONS: As expected by state mandate, significantly more
      seventh, eight, and ninth graders were immunized compared to students in grades
      10 through 12 (X(2) = 137.50, p < 0.0001). More than 90% of the students in the
      seventh, eight, and ninth grades had received all three hepatitis B vaccines.
      Less than 30% of the students in grades 10 through 12 received all three
      vaccines. Most parents (79%) said their high school-aged children had not
      received the vaccines because they were not required to do so. Most parents knew
      children needed three vaccines to be fully immunized and correctly identified the
      liver as the target organ. However, there was uncertainty about the mode of HBV
      transmission.

PMID- 11846365
TI  - Developing partnerships in Washington State to prevent hepatitis B virus
      infection in Asian Americans and Pacific Islanders.
AB  - PURPOSE: The purpose of this paper is to describe the partnerships and activities
      of the Washington State Asian and Pacific Islander Task Force on Hepatitis B
      Immunization to: 1) increase hepatitis B vaccination of older Asian American and
      Pacific Islander (AAPI) children and 2) prevent hepatitis B virus (HBV) infection
      in Washington State. METHODS: Multiple strategies were used to increase hepatitis
      B vaccination rates among AAPI children, including developing a Task Force
      consisting of members from public and private organizations. Specific strategies
      included: 1) developing and distributing culturally specific hepatitis B
      educational materials, 2) supporting a household cluster survey to assess
      hepatitis B vaccination coverage rates of AAPI children, 3) conducting hepatitis
      B immunization and blood testing clinics at local Chinese language schools, and
      4) conducting outreach through media sources. PRINCIPAL FINDINGS: Hepatitis B
      vaccination data from two clinics with large numbers of AAPI clients were
      evaluated for children aged 0 to 19 years. The results suggest that the average
      number of hepatitis B vaccinations given per month has been increasing between
      1995 through March 2001. Although no causal association between vaccination rates
      and activities of the Task Force can be made, these data suggest that our efforts
      may have had a positive impact. CONCLUSIONS: Hepatitis B prevention efforts in a
      high-risk community can be accomplished in partnership with the AAPI community
      and organizations working with these communities. Collaborations require
      persistence, patience, flexibility, and creativity to achieve community and
      public health goals.

PMID- 11846366
TI  - Hepatitis B Catch-Up Project: analysis of 1999 data from the Chicago Public
      Schools.
AB  - PURPOSE: Asian American Pacific Islander (AAPI) children face an increased risk
      for acquiring hepatitis B virus infection. Since 1990, the Centers for Disease
      Control and Prevention have recommended universal hepatitis B immunization for
      AAPI children. In 1997, Illinois passed a law requiring hepatitis B vaccination
      for school entry, but its implementation was restricted to pre-kindergarten and
      fifth-grade students. That same year, the Illinois Health Education Consortium
      (IHEC) began the Hepatitis B Immunization Catch-Up Project in collaboration with
      the Chicago Public Schools (CPS) and community organizations. Schools targeted
      for IHEC intervention were those enrolling more than 100 (or over 20%) AAPI
      students. This study describes the effects of the Illinois law and the Hepatitis
      B Immunization Catch-Up Project on hepatitis B immunization of AAPI students in
      the CPS in 1999. METHODOLOGY: The effects of the IHEC Catch-Up Project
      intervention and the Illinois law upon hepatitis B immunization was tested using
      a two-way analysis of variance for the 1999-2000 cohort of AAPI students enrolled
      in the CPS as of November 1999. PRINCIPAL FINDINGS: Results indicated students
      required to receive hepatitis B immunization shots received a significantly (p <
      .001) higher mean number of shots than was the case for students who were not
      required to receive the shots. Similarly, IHEC-intervention students received a
      significantly (p < .001 ) higher mean number of shots than was the case for
      students who were not part of the IHEC intervention. CONCLUSIONS: The IHEC
      intervention produced a significant, positive effect on the hepatitis B
      immunization rate above and beyond the state law. The practical significance of
      the IHEC intervention is described and discussed.

PMID- 11846368
TI  - A survey of vaccinations of immigrants and refugees in San Diego County,
      California.
AB  - PURPOSE: This report summarizes a vaccination coverage survey of 65 immigrant and
      refugee families in San Diego County. It included gathering information from 19
      community and government organizations on the immunization system, and on
      families' barriers impeding immunization. METHODS: The "rapid appraisal"
      exploratory method flexibly used several research methods, such as informant
      interviews and door-to-door surveys, changing methods as new questions were
      uncovered. The researcher went alone, or with organizations' staffs, to interview
      families, record their vaccination records, and give them forms telling which
      vaccine doses they lacked. PRINCIPAL FINDINGS: The 4:3:1 (4 DTP, 3 polio, 1 MMR)
      vaccination series completion rate among children while they were aged 19-35
      months old ranged from 33% in those born in 1984-1985, to 60% in those born in
      1996-1997. The hepatitis B vaccine completion coverage rate among children in the
      1984-1993 birth cohorts was 73%. The hepatitis B vaccine completion coverage rate
      among Hmong, Vietnamese, and Chinese adolescents ranged from 86%-100%, and among
      the Kurdish was 85%, Somali 73%, Lao 43% and Cambodian adolescents 35%.
      CONCLUSIONS: The hepatitis B vaccine completion coverage rate was higher among
      Hmong, Vietnamese, and Chinese adolescents probably because they lived near
      clinics and schools providing the vaccine to many, and among the Kurdish and
      Somali because they received many doses in refugee programs. The families
      experienced immunization barriers involving transportation, languages, little
      knowledge of immunizations, and missed opportunities. Two populations have
      cultural barriers: numerous European-Americans believe in anti-vaccine ideas; and
      many East Africans have little knowledge of the English language and the American
      system. RECOMMENDATIONS: Health personnel should continue using current methods
      to promote immunizations. Community organizations' staffs should consistently
      check vaccination records, and health officials should do more trainings for
      those staffs. The National Task Force on Hepatitis B Immunization, Focus on
      Asians and Pacific Islanders should broaden its work from Asians and Pacific
      Islanders, to other nationalities with intermediate or high hepatitis B
      endemicity.

PMID- 11846367
TI  - Vaccinating Asian Pacific Islander children against hepatitis B: ethnic-specific
      influences and barriers.
AB  - PURPOSE: Hepatitis B virus (HBV) is a known cause of liver cancer, especially
      among Asian and Pacific Islanders (API). Despite national recommendations and
      school entry requirements for vaccination, many children are not fully vaccinated
      with the Hepatitis B vaccine (Hep B) before entering school. The purpose of this
      study was to measure ethnic group-specific hepatitis B vaccination rates among
      school-aged API children after implementation of universal recommendations and
      school laws, and quantify ethnic-specific risk factors associated with late and
      incomplete vaccinations. METHODS: A multilingual questionnaire was distributed to
      parents of second and fourth graders in nine Los Angeles County (LAC) elementary
      schools with high proportions of API students. Data on Hepatitis B vaccination
      dates, source of health care and health information, cultural factors, and
      general knowledge and attitudes about HBV and vaccination were collected and
      analyzed. FINDINGS: Overall, 1,696 (77%) of 2,183 questionnaires were returned.
      Of these, 1,024 were from API children. The API second graders in this survey had
      a 72% coverage rate, ranging from 46% to 94% among the individual ethnic groups.
      Fifty-one percent of API fourth graders had three doses of Hep B vaccine, ranging
      from 38% to 69% among the individual ethnic groups. Factors influencing coverage
      levels among API fourth graders were speaking limited English at home, living in
      the United States less than five years, and not having discussed hepatitis B
      vaccination with a health care provider. Factors influencing low immunization
      levels differed among the API ethnic groups. CONCLUSIONS: Analysis and
      intervention on a non-aggregate level are necessary for designing both effective
      and cultural-specific outreach programs for diverse API communities such as
      LAC's.

PMID- 11846370
TI  - Extraction of nucleic acid fragments from gels.

PMID- 11846371
TI  - 3-Nitrotyrosine butyl ester: a novel derivative to assess tyrosine nitration in
      rat plasma by liquid chromatography-tandem mass spectrometry detection.
AB  - A novel, sensitive, and specific method is presented for the quantification of
      endogenous 3-nitrotyrosine in rat plasma based on isotope dilution liquid
      chromatography-electrospray ionization tandem mass spectrometry, using 3-nitro
      2,5,6-d(3)-l-tyrosine as an internal standard. The extraction and cleanup method
      entails three major steps: protein precipitation, solid-phase extraction with an
      aminopropyl cartridge, followed by derivatization of 3-nitrotyrosine to the
      corresponding butyl ester. The analysis of the stable butyl ester derivative
      circumvented matrix interferences, which were encountered on the analysis of the
      nonderivatized analyte in plasma, and thus significantly improved sensitivity.
      The mass spectral acquisition of 3-nitrotyrosine butyl ester was done in the
      positive ion mode using selected reaction monitoring of two specific transitions.
      The response was linear over the concentration range 1.4-28.5 nM, and the
      recoveries of spiked 3-nitrotyrosine in rat plasma exceeded 75%. The detection
      and quantification limits of 3-nitrotyrosine in rat plasma (165 microL equivalent
      injected) approached 0.43 and 1.4 nM (0.07 and 0.23 pmol, on column),
      respectively. This study also addresses the potential artifactual formation of 3
      nitrotyrosine, which may lead to an overestimation of the background levels of
      the biomarker. Solid-phase extraction of 3-nitrotyrosine was required prior to
      esterification to avoid artifactual nitration of tyrosine. In this context,
      analysis of eight rat plasma samples showed quantifiable levels in only four of
      the samples of the order of 1.4-1.5 nM.

PMID- 11846372
TI  - Cascade blue as a donor for resonance energy transfer studies of heme-containing
      proteins.
AB  - Cascade Blue acetyl azide is an amine reactive compound with spectral properties
      ideally suited for fluorescence resonance energy transfer (FRET) studies in which
      heme prosthetic groups serve as acceptors. To demonstrate utility of the Cascade
      Blue-heme spectroscopic ruler, cytochrome c was employed as a test case to
      calibrate distance measurements obtained from FRET analysis. Following
      modification, stoichiometrically labeled cytochrome c was digested with trypsin
      and derivatized fragments were analyzed by matrix-assisted laser
      desorption/ionization and electrospray ionization mass spectrometry to identify
      Lys25 as the predominant site of covalent modification. FRET analysis on
      derivatized protein demonstrated nearly complete quenching of Cascade Blue
      fluorescence, indicating the labeled lysine residue to reside within 30 A of the
      heme prosthetic group. Sodium dodecyl sulfate (SDS) denaturation resulted in an
      approximately 28% recovery of fluorescence, demonstrating the utility of this
      donor-acceptor pair for evaluating distance changes of 30-90 A. Modeling the
      Cascade Blue donor molecule onto Lys25 of a cytochrome c NMR structure confirmed
      a distance of < or =30 A from the heme acceptor, as determined by FRET analysis.
      Further modeling of the SDS-denatured state as an extended chain suggested a
      maximum separation distance of 45 A, also consistent with results derived from
      FRET analysis.

PMID- 11846373
TI  - Real-time analysis of ligand-induced cell surface and intracellular reactions of
      living mast cells using a surface plasmon resonance-based biosensor.
AB  - Surface plasmon resonance (SPR)-based sensors have been used to detect the
      binding between interactive molecules. We applied the SPR technology to the
      analysis of interactions between living cells and molecules reactive to the
      cells, using mast cells and mast cell-reactive antigens. The exposure of
      dinitrophenol-human serum albumin (DNP-HSA), an antigen that stimulates mast
      cells, to IgE-sensitized mast cells induced a robust and long-lasting SPR signal
      in a dose-dependent manner. The maximal increase in SPR signal induced by 100
      ng/ml DNP-HSA was 0.200 +/- 0.120 angle (mean +/- SD, n = 37), about 1000 times
      larger than the theoretically expected increase for the simple binding of DNP-HSA
      to Fc(epsilon)RI, the high-affinity IgE receptor. A small, but similarly
      prolonged signal was observed when the cells were stimulated by an agonist of the
      adenosine A3 receptor. The signal induced by DNP-HSA was abolished by genistein,
      and partially inhibited by phorbol 12-myristate 13-acetate and wortmannin.
      Interestingly, the signal induced by DNP-HSA was only weakly inhibited by DNP
      lysine, suggesting that DNP-lysine manifests its action not by inhibiting, but by
      modulating the crosslinking of Fc(epsilon)RI. We concluded that SPR sensors can
      detect biologically significant signals in a real-time manner from the
      interactions between cells and molecules reactive to the cells.

PMID- 11846374
TI  - Microarray analysis of E-box binding-related gene expression in young and
      replicatively senescent human fibroblasts.
AB  - An E-box (CACGTG) designer microarray was developed to monitor a group of genes
      whose expressions share a particular regulatory mode. Sensitivity and specificity
      of microarray hybridization, as well as variability of microarray data, were
      evaluated. This designer microarray was used to generate expression profiles of E
      box binding-related genes in WI-38 fibroblast cultures at three different growth
      states: low-passage replicating, low-passage contact-inhibited quiescent, and
      replicatively senescent. Microarray gene screening reveals that quiescent and
      senescent cells, in comparison with replicating ones, are characterized by
      downregulation of Pam, a protein associated with c-Myc, and upregulation of Mad
      family genes, Max dimerization proteins. Moreover, quiescence and senescence can
      be distinguished by increased expression of Irlb, c-Myc transcription factor, and
      Miz-1, c-Myc-interacting Zn finger protein 1, only in the former state.
      Senescence is characterized by downregulation of Id4, inhibitor of DNA binding 4,
      and Mitf, microphthalmia-associated transcription factor, in comparison with
      young replicating and quiescent states. Differential expression of genes detected
      by microarray hybridization was independently confirmed by reverse transcription
      polymerase chain reaction technique. Alterations in the expression of E-box
      binding transcription factors and c-Myc-binding proteins demonstrate the
      importance of these genes in establishing the contact-inhibited quiescent or
      senescent phenotypes.

PMID- 11846375
TI  - A new quantitative method of real time reverse transcription polymerase chain
      reaction assay based on simulation of polymerase chain reaction kinetics.
AB  - Real-time reverse transcription (RT) PCR is currently the most sensitive method
      for the detection of low-abundance mRNAs. Two relative quantitative methods have
      been adopted: the standard curve method and the comparative C(T) method. The
      latter is used when the amplification efficiency of a reference gene is equal to
      that of the target gene; otherwise the standard curve method is applied. Based on
      the simulation of kinetic process of real-time PCR, we have developed a new
      method for quantitation and normalization of gene transcripts. In our method, the
      amplification efficiency for each individual reaction is calculated from the
      kinetic curve, and the initial amount of gene transcript is derived and
      normalized. Simulation demonstrated that our method is more accurate than the
      comparative C(T) method and would save more time than the relative standard curve
      method. We have used the new method to quantify gene expression levels of nine
      two-pore potassium channels. The relative levels of gene expression revealed by
      our quantitative method were broadly consistent with those estimated by routine
      RT-PCR, but the results also showed that amplification efficiencies varied from
      gene to gene and from sample to sample. Our method provides a simple and accurate
      approach to quantifying gene expression level with the advantages that neither
      construction of standard curve nor validation experiments are needed.

PMID- 11846376
TI  - Isolation of hepatic mitochondrial contact sites: previously unrecognized inner
      membrane components.
AB  - An improved, fast, and relatively simple procedure for isolation of hepatic
      mitochondrial contact sites is described. These contact sites include
      conventional outer membrane, but the inner membrane component (which we term
      fusion patches) has a unique biochemical composition characterized by a
      clustering of three specific inner membrane proteins of 54, 52, and 31 kDa
      identified by proteomics, respectively, as the alpha and beta subunits of ATP
      synthase and the liver isoform of adenine nucleotide transferase. The contact
      site fraction was prepared using a discontinuous sucrose gradient from crude
      outer membranes derived from swollen/shrunk rat liver mitochondria. The resultant
      contact sites were analyzed using a continuous sucrose density gradient,
      revealing an apparent heterogeneity due to varying amounts of retained fusion
      patches in relation to the unvarying outer membrane component. By electron
      microscopy, contact sites consist of small vacuoles that contain one or several
      tiny vesicles, many of which are composed of multiple, closely packed lamellae.
      The contact site subfraction morphology is consistent with the biochemical
      variation. Thus, contact sites are not haphazard fusions of outer and inner
      membrane, but consist in part of regions of inner membrane of novel composition
      (fusion patches) and of conventional outer membrane.

PMID- 11846377
TI  - Chemoenzymatic synthesis of peptidyl 3,4-dihydroxyphenylalanine for structure
      activity relationships in marine invertebrate polypeptides.
AB  - An improved method for hydroxylating tyrosine-containing sequences in
      polypeptides to peptidyl 3,4-dihydroxyphenylalanine (DOPA) using mushroom
      tyrosinase at relatively high enzyme-to-substrate ratios is described. The new
      method involves incorporating borate into the reaction mixture to stop formation
      of the unwanted side product 3,4,5-trihydroxyphenylalanine. Using this method, a
      model for the palindromic central sequence for the antimicrobial peptide family,
      the styelins, Y*Y*KHKY*Y* (where Y* is DOPA), was successfully synthesized in
      high yield from YYKHKYY. This sequence represents a particularly challenging
      target because of the cluster of four precursor tyrosine residues are in close
      proximity. The method should be readily applied to larger polypeptides produced
      by either solid-phase synthesis or recombinant techniques and give greater
      insight into the roles of this unusual posttranslational modification in marine
      invertebrates such as mussels and ascidians.

PMID- 11846378
TI  - Methodologies for monitoring nanoparticle formation by self-assembly of DNA with
      poly(l-lysine).
AB  - DNA self-assembly with polycations produces nanoparticles suitable for gene
      delivery, although there is no standard methodology to measure particle formation
      and stability. Here we have compared three commonly used assays, namely, light
      scattering, inhibition of ethidium bromide fluorescence, and modified
      electrophoretic mobility of DNA. Analysis by light scattering and loss of
      ethidium bromide fluorescence both showed poly(l-lysine) (pLL)/DNA nanoparticles
      form over the lysine/phosphate ratio range 0.6-1.0, although retardation of DNA
      electrophoretic mobility commenced at lower lysine/phosphate ratios. This
      probably indicates that the first two assays monitor DNA collapse into particles,
      while the electrophoresis assay measures neutralization of the charge on DNA. Gel
      analysis of the complexes showed disproportionation during nanoparticle
      formation, probably reflecting cooperative binding of the polycation. The assays
      were used to examine stability of complexes to dilution in water and
      physiological salts. Whereas all pLL/DNA nanoparticles were stable to dilution in
      water, the presence of physiological salts provoked selective disruption of
      complexes based on low-molecular-weight pLL. Polyelectrolyte complexes for
      targeted application in vivo should therefore be based on high-molecular-weight
      polycations, or should be stabilized to prevent their dissociation under
      physiological salt conditions.

PMID- 11846379
TI  - Probing reactive center loop insertion in serpins: a simple method for ovalbumin.
AB  - Insertion of the reactive center loop in beta-sheet A in serpins has been
      typically inferred from the increased stability of the cleaved form to thermal-
      and urea-induced denaturation. We describe a convenient and rapid fluorescence
      based method that differentiates the loop-inserted form from the loop-exposed
      form in ovalbumin, a prototypic noninhibitory serpin. Recombinant wild-type and
      R345A ovalbumins in the intact form bind ANS with equilibrium dissociation
      constants of 116 and 125 microM and a maximal fluorescence increase of 200 and
      264%, respectively, in pH 6.8 buffer. Cleavage of the two proteins with porcine
      pancreatic elastase results in a 1.6- and 2.6-fold increase in the ANS-binding
      affinity. While cleavage of the reactive center loop in rR345A ovalbumin results
      in a approximately 200% increase in the ANS fluorescence, the rWT protein
      exhibits a approximately 50% decrease. Similar experiments with alpha(1)
      proteinase inhibitor and antithrombin, two inhibitory serpins that exhibit
      reactive center loop insertion, show a decrease in ANS fluorescence on cleavage
      with porcine pancreatic elastase and thrombin, respectively. Denaturation studies
      in guanidinium hydrochloride indicate that the reactive center loop is inserted
      in the main body of the serpin in the cleaved form of rR345A mutant, while it is
      exposed in the cleaved form of rWT ovalbumin. These results demonstrate that ANS
      fluorescence change is an indicator of the loop-inserted or loop-exposed form in
      these recombinant ovalbumins, and thus could be advantageously used for probing
      reactive center loop insertion in ovalbumins. The major increase in fluorescence
      for the rR345A mutant on cleavage primarily arises from a change in ANS binding
      rather than from the generation of an additional ANS-binding site.

PMID- 11846380
TI  - Thermus scotoductus and Rhodothermus marinus DNA ligases have higher ligation
      efficiencies than thermus thermophilus DNA ligase.
AB  - To mimic large numbers of nicked DNA duplexes we used a technique that produces
      nicked duplex DNA substrates by hybridization of complementary oligonucleotides,
      adjacent to an initiating primer, which are ligated together by a thermostable
      DNA ligase. Sequential ligation of nonanucleotides to this primary duplex results
      in the formation of polymers that can be analyzed by gel electrophoresis. The
      extent of polymerization is a measure of the efficiency of ligation. We
      determined the efficiency of ligation of nonanucleotides, using various length
      initiating primers, with three thermostable DNA ligases: Thermus thermophilus
      (Tth), Thermus scotoductus (Ts), and Rhodothermus marinus (Rm). Analysis of the
      effect of temperature for each ligase, and for each directing primer length,
      revealed that at 37 and 41 degrees C there was variation between ligase
      efficiency in the order Rm > or = Ts > or = Tth. The higher temperature of 46
      degrees C was optimal for polymerization with each of the ligases and Rm ligase
      was the most efficient. Analysis of directionality of the ligations reactions
      suggests that for each of the Thermus ligases we tested, there was a bias to
      polymerization of nonanucleotides in a 5'-3' direction.

PMID- 11846381
TI  - Capillary electrophoretic assay and purification of cylindrospermopsin, a
      cyanobacterial toxin from Aphanizomenon ovalisporum, by plant test (blue-green
      Sinapis test).
AB  - Toxic cyanobacteria are known to produce cyanotoxins, toxic secondary
      metabolites. In recent years the cylindrospermopsin (tricyclic guanidinyl
      hydroxymethyluracil)-producing organisms Aphanizomenon ovalisporum,
      Cylindrospermopsis raciborskii, and Umezakia natans have been inhabiting polluted
      fresh waters. Cylindrospermopsin, a potent hepatotoxic cyanotoxin, has been
      implicated in cases of human poisoning as well. This study describes the
      isolation and purification of cylindrospermopsin from A. ovalisporum with the
      help of a slightly modified Blue-Green Sinapis Test, a plant test suitable for
      determining the cyanotoxin content of chromatographic fractions besides plankton
      samples. The recent modification, using microtiter plates for the assay, improves
      the method and reduces the amount of sample needed for the assay. This approach
      proved that plant growth and metabolism, at least in the case of etiolated
      Sinapis alba seedlings, are inhibited by cylindrospermopsin. The establishment of
      capillary electrophoresis of cylindrospermopsin and consideration of the results
      reported here lead us to the expectation that capillary electrophoresis of
      cylindrospermopsin may be a powerful and useful analytical method for
      investigating cyanobacterial blooms for potential cylindrospermopsin content and
      toxicity. Confirmation of chemical identity of the purified compound is performed
      by UV spectrophotometry, NMR, and MALDI-TOF.

PMID- 11846382
TI  - Hepatocyte membrane water permeability measured by silicone layer filtering
      centrifugation.
AB  - We previously found that hepatocytes are able to control their osmotic membrane
      water permeability (P(f)) by regulating the number of surface aquaporin water
      channels. Hepatocyte P(f) has been assessed by phase-contrast microscopy and cell
      image analysis, an established but relatively laborious procedure. We report here
      an alternative method to assess hepatocyte P(f) based on a single silicone layer
      filtering centrifugation system. Isolated rat hepatocytes were incubated in
      hypotonic or isotonic buffers containing (3)H(2)O as a tracer and, then, were
      filtered by rapid centrifugation through a silicone layer down to a lysis layer.
      Osmotically driven radioactivity (i.e., (3)H(2)O) within hepatocytes was
      calculated as the difference between the dpm in lysis media measured under
      hypotonic and isotonic conditions. The P(f) calculated from the initial slope of
      the radioactivity-versus-time curve was 18 microm/s at 4 degrees C. Hepatocytes
      treated with dibutyryl cyclic AMP, to increase P(f) through the plasma membrane
      insertion of aquaporins, showed an increased P(f) value of 37 microm/s. The
      aquaporin blocker dimethyl sulfoxide selectively prevented the agonist-induced
      hepatocyte P(f). These data are in good agreement with the corresponding values
      determined by quantitative phase-contrast microscopy; thus, the method developed
      allows the rapid and reliable measurement of hepatocyte P(f).

PMID- 11846383
TI  - C-terminal sequence analysis of peptides using triphenylgermanyl isothiocyanate.
AB  - The Schlack-Kumpf degradation, also called the isothiocyanate method, is thought
      to be a promising approach to chemical C-terminal sequencing of peptides and
      proteins. The derivatizing reagent is most crucial to this method. A new
      derivatizing reagent, triphenylgermanyl isothiocyanate (TPG-ITC), has been
      synthesized and applied to C-terminal peptide sequencing. The chemistry involves
      activation with acetic anhydride, derivatization with TPG-ITC, and cleavage of
      the derivatized C-terminal amino acid thiohydantoin with sodium hydroxide. A
      series of reaction conditions, including activation reagent volume, activation
      time, and derivatization temperature and time, have been investigated using a
      model peptide covalently attached to 1,4-phenylene diisothiocyanate (DITC)-glass
      beads. This procedure has been successfully used to sequence eight C-terminal
      residues of a model peptide at low nanomole levels. TPG-ITC is a white solid with
      relatively long shelf-life. According to our previous article (B. Mo, J. Li, and
      S. P. Liang, 1997, Anal. Biochem. 252, 169-176), TPG-ITC is a type II
      derivatizing reagent. Compared with acetyl isothiocyanate and trimethylsilyl
      isothiocyanate, TPG-ITC is much more stable and efficient for use in peptide C
      terminal sequencing.

PMID- 11846384
TI  - A colorimetric assay for the quantitation of free adenine applied to determine
      the enzymatic activity of ribosome-inactivating proteins.
AB  - Adenine quantitation is required for a variety of applications. To date, the
      prevalent method for quantifying free adenine, in a variety of applications, is
      the detection of fluorescent-derivatized adenine by HPLC. For the present study,
      we developed a high-throughput, nonradioactive, enzyme-based colorimetric adenine
      quantitation assay that is performed in one multireaction incubation step. The
      assay does not require adenine derivatization and is designed for microplates.
      The key step is the conversion of adenine to adenosine monophosphate by adenine
      phosphoribosyl transferase. Subsequent reactions finally produce three inorganic
      phosphate ions per adenine molecule. Phosphate is quantitated by the color
      generating phosphorylysis of a particular purine derivate. Ribosome-inactivating
      proteins that release adenine from polynucleotides are often used to investigate
      intracellular protein trafficking and are important for the design of
      immunotoxins. We therefore used ricin, dianthin, saporin, and a variety of
      saporin fusion proteins to show that this method is suitable for quantifying
      adenine release using different substrates. The measured rate of adenine release
      and substrate specificity are comparable to those determined by HPLC and
      radioactive detection techniques.

PMID- 11846385
TI  - Identification and characterization of hydrophobic Escherichia coli virulence
      proteins by liquid chromatography-electrospray ionization mass spectrometry.
AB  - Virulence of enterotoxicogenic Escherichia coli is mediated by rodlike, rigid,
      highly hydrophobic proteins designated fimbriae or colonization factors (CFs).
      More than 20 different colonization factors have been described so far using
      predominantly immunological and genetic methods. To characterize these
      hydrophobic proteins by liquid chromatography-mass spectrometry (LC-MS),
      different methodologies were explored. A novel LC-MS method was developed using
      hexafluoroisopropanol to maintain the hydrophobic proteins in solution. In
      addition, these proteins were digested with cyanogen bromide and peptide mapping
      by LC-MS was established. This technique was particularly useful in
      identification of closely related CFs. Both LC-MS and peptide mapping
      methodologies were found to be useful in characterizing highly hydrophobic CFs of
      E. coli. To search for molecular weights of mature proteins in the National
      Center for Biotechnology Information (NCBI) database, a new feature was developed
      and its applicability tested. The identification of a class of pathogenic
      virulence proteins, either intact or digested, is possible with molecular weight
      database searching.

PMID- 11846386
TI  - High-performance liquid chromatographic assay for N-glucuronidation of nicotine
      and cotinine in human liver microsomes.
AB  - A method for the determination of N-glucuronidation of nicotine and cotinine in
      human liver microsomes by high-performance liquid chromatography was developed.
      Nicotine or cotinine was incubated with human liver microsomes and UDP-glucuronic
      acid in a 200-microl incubation mixture. The nicotine N-glucuronide (Nic-glu) and
      cotinine N-glucuronide (Cot-glu) formed were analyzed by ion-pair chromatography
      with a C-18 column. The sensitivity of quantification at 260 nm absorption was
      improved by using a noise-base clean Uni-3, and the limit of quantification was
      10 pmol/200 microl mixture for both Nic-glu and Cot-glu. Linear standard curves
      were obtained within the concentration ranges 25-1000 pmol/200 microl mixture for
      Nic-glu and 100-5000 pmol/200 microl mixture for Cot-glu. The intraassay
      precision and accuracy were < or =11.1% coefficient of variation (CV) and 97.5
      106.6% for Nic-glu and < or =4.6% CV and 96.7-100.4% for Cot-glu. The interassay
      precision and accuracy were < or =7.2% CV and 98.2-106.1% for Nic-glu and < or
      =4.6% CV and 96.8-99.3% for Cot-glu. This is the first report of the in vitro
      determination of Nic-glu and Cot-glu in human liver microsomes. Furthermore, this
      highly sensitive HPLC method can be used for the determination of Nic-glu and Cot
      glu in biological specimens in vivo.

PMID- 11846387
TI  - Monitoring differential synthesis of RNA in individual cells by capillary
      electrophoresis.
AB  - A capillary electrophoresis (CE)-based technique is reported here to monitor
      differential RNA synthesis in individual Chinese hamster ovary cells at distinct
      stages of the cell proliferation cycle. Cell synchronization was achieved by the
      shake-off method, in which mitotic (M) cells were dislodged, and cells at G(1),
      S, and G(2) phases were harvested 2.5, 10, and 13 h, respectively, after
      synchronizing the mitotic cells. Thirty-two cells (eight from each phase) were
      analyzed by injecting each cell into the capillary, lysing it with dilute
      surfactant, separating the RNA by capillary electrophoresis, and detecting the
      peaks with laser-induced fluorescence. The results from single cells show that
      the total amount of RNA increased at each successive stage (from G(1) to M),
      while the relative synthetic rates of different RNA fractions varied with
      progression through the cycle. There was a threefold increase in the synthetic
      rate of total RNA from S to G(2), compared with G(1) to S. In addition,
      differential accumulation of specific RNA fractions was observed, with the low
      molecular-mass fraction exhibiting a much higher synthetic rate from G(2) to M,
      relative to the rates of the larger ribosomal RNA (rRNA) fractions. Comparison of
      the large rRNA fractions with one another reveals that at S phase more 28S rRNA
      was accumulated than 18S rRNA, and at G(1) and M phases, the synthetic rate of
      28S rRNA was slowed compared with that of 18S. Minimal sample preparation,
      combined with the separation power of CE and single-cell detection sensitivity of
      laser-induced fluorescence, results in a simple method for assessing differential
      accumulation of RNA from distinct individual cells.

PMID- 11846388
TI  - Determination of the volumetric properties of proteins and other solutes using
      pressure perturbation calorimetry.
AB  - Pressure perturbation calorimetry is a new technique that measures the heat
      change in a solution that results when the pressure above the solution is
      changed. When used in a differential calorimeter containing a dilute solution of
      solute in the sample cell and the corresponding buffer in the reference cell, the
      measured differential heat can be used to calculate the thermal coefficient of
      expansion of the partial volume of the solute, alpha. For proteins in dilute
      aqueous solution, alpha is dominated by a temperature-dependent contribution
      arising from the interaction of protein groups with water at the protein-solvent
      interface. This arises due to the effect of the protein groups on the hydrogen
      bonded structure of water, and thereby clearly differentiates between structure
      making hydrophobic groups and structure-breaking hydrophilic groups. This
      solvation contribution to alpha can be accentuated in solvents having more
      structure (deuterium oxide) than water and attenuated in solvents having less
      structure (2.8 M guanidinium sulfate). Six different proteins (chymotrypsinogen,
      pepsinogen, lysozyme, bovine pancreatic trypsin inhibitor, ribonuclease A, and T4
      lysozyme) were examined carefully by this technique, allowing estimates of
      various volumetric parameters including the volume change resulting from thermal
      unfolding of each protein. For ribonuclease A, results obtained in both water and
      deuterium oxide led to an estimate of the accessible surface area of the native
      protein of approximately 45% relative to the fully reduced unfolded protein.
      Also, it was also found that ligand binding to ribonuclease A led to changes in
      alpha, suggesting a burial of some surface area in the ligand-protein complex.

PMID- 11846389
TI  - The EGF-like homeotic protein dlk affects cell growth and interacts with growth
      modulating molecules in the yeast two-hybrid system.
AB  - Levels of dlk, an EGF-like homeotic protein, are critical for several
      differentiation processes. Because growth and differentiation are, in general,
      exclusive of each other, and increasing evidence indicates that Dlk1 expression
      changes in tumorigenic processes, we studied whether dlk could also affect cell
      growth. We found that, in response to glucocorticoids, Balb/c 3T3 cells with
      diminished levels of dlk expression develop foci-like cells that have lost
      contact inhibition, display altered morphology, and grow faster than control cell
      lines. Balb/c 3T3 cells spontaneously growing more rapidly are also dlk-negative
      cells. Moreover, screening by the yeast two-hybrid system, using Dlk1 constructs
      as baits, resulted in the isolation of GAS1 and acrogranin cDNAs. Interestingly,
      these proteins are cysteine-rich molecules involved in the control of cell
      growth. Taken together, these observations suggest that dlk may participate in a
      network of interactions controlling how the cells respond to growth or
      differentiation signals.

PMID- 11846390
TI  - DNA chain unwinding and annealing reactions of lipocortin (annexin) I
      heterotetramer: regulation by Ca(2+) and Mg(2+).
AB  - Lipocortin I-S100 (calcyclin) heterotetramer exhibited ATPase activity in the
      presence of dsDNA but not ssDNA. To demonstrate its helicase activity, an 80-mer
      polynucleotide complementary to the replication origin of M13mp18 was
      synthesized, and the oligonucleotide, (dC)(20), was ligated to either its 5'- or
      3'- end for binding to lipocortin. Lipocortin I heterotetramer displaced chains
      of the partially Y-shaped duplexes with a dC-tail at either the 5'- or 3'- end.
      The chain displacement required ATP and Mg(2+). Nonhydrolyzable ATP analogues
      were not effective. Lipocortin I heterotetramer also catalyzed annealing of the
      polynucleotides to M13mp18. Ca(2+) and phospholipids but not ATP and Mg(2+) were
      essential for this reaction. Since the chain displacing and annealing reactions
      were inhibited by monospecific anti-lipocortin I or anti-S100 antibodies, the
      present observations suggest that the lipocortin I heterotetramer regulates
      unwinding and annealing of DNA by Mg(2+) (plus ATP) and Ca(2+) (and
      phospholipids), respectively.

PMID- 11846391
TI  - Interchromosomal telomere length variation.
AB  - Despite the recent discovery of interchromosomal telomere length variation, a
      role for heterogeneity in telomere maintenance has yet to be established. This
      study aimed to clarify relative telomere length differences between chromosomes.
      Combined chromosomal sorting and telomeric repeat content analysis in GM130B
      cells, the relative telomeric repeat content in each chromosome, were calculated.
      Each chromosome could be isolated except for chromosomes 1 and 2 and chromosomes
      9 to 12, which were isolated in a group. Telomere length was correlated with the
      size of the corresponding chromosome. Concomitant relative telomeric repeat
      content analysis in each chromosome and terminal restriction fragment analysis
      using the whole genome revealed that the terminal restriction fragments of each
      chromosome were heterogenously distributed through the smear of the fragments.
      This is the first description of an association between telomere length and
      chromosome size.

PMID- 11846392
TI  - Inhibition of the mitochondrial permeability transition by aldehydes.
AB  - Fructose has been shown to protect hepatocyte viability during hypoxia or
      exposure to mitochondrial electron transport inhibitors. We report here that the
      fructose metabolite D-glyceraldehyde (D-GA) is a good inhibitor of the
      mitochondrial permeability transition pore (PTP) in isolated rat liver
      mitochondria. We propose that a substantial portion of the protective effect of
      fructose on hepatocytes is due to D-GA inhibition of the permeability transition.
      Aldehydes which are substrates of the mitochondrial aldehyde dehydrogenase
      (mALDH) afford protection, while poor substrates do not. Protection is prevented
      by the ALDH inhibitor chloral hydrate. We propose that the NADH/NAD(+) ratio is
      the key to protection. The aldehydes phenylglyoxal (PGO) and 4-hydroxynonenal (4
      HNE), which have previously been shown to inhibit the PTP, apparently function by
      a different mechanism independent of mALDH activity. Both PGO or 4-HNE are
      themselves potent inhibitors of ALDH, and their protective effect cannot be
      blocked by an ALDH inhibitor.

PMID- 11846394
TI  - Avian TVB (DR5-like) death receptor expression in hen ovarian follicles.
AB  - TVB is an avian death domain-containing receptor belonging to the TNF receptor
      family and is proposed to be the ortholog to mammalian DR5. Although TVB receptor
      activation has been demonstrated to mediate apoptosis in chick embryo
      fibroblasts, there is essentially no information regarding TVB expression or
      regulation in the mature hen ovary, and in particular within the follicle
      granulosa layer where apoptosis is known to promote atresia. Significantly, the
      TVB receptor represents the fourth death domain-containing receptor (also
      including Fas, TNF-R1, and DR6) found to be expressed within hen granulosa cells.
      Levels of TVB expression are higher in prehierarchal follicles actively
      undergoing atresia compared to healthy follicles. However, increased TVB
      expression does not precede follicle death induced in vitro. Furthermore, TVB
      expression within granulosa cells is highest during the final stages of follicle
      development when follicles are not normally susceptible to undergoing atresia.
      These results provide evidence that TVB receptor signaling in the ovary may
      function in a capacity other than solely to mediate granulosa cell death and
      follicle atresia.

PMID- 11846393
TI  - Characterization of a cytochrome b(558) ferric/cupric reductase from rabbit
      duodenal brush border membranes.
AB  - Iron and probably also copper are absorbed by the intestine in their reduced
      form. A b-type cytochrome, Dcytb, has recently been cloned from mouse and has
      been proposed to be the corresponding reductase. However, the nature of the
      cytochrome and the reduction reaction remain unknown. Here we describe the
      isolation and functional characterization of a novel b-type cytochrome from
      rabbit enterocytes. The 33 kDa heme protein was solubilized from brush border
      membranes with Triton X-100 and purified by successive ion exchange
      chromatography and hydrophobic interaction chromatography. Spectroscopic analysis
      of the heme revealed a b(558) cytochrome. The purified hemoprotein exhibited
      ascorbate-stimulated reduction of iron(III) and copper(II). The rate constants,
      k(1), for these reactions were 1.38 +/- 0.12 and 0.64 +/- 0.16 min(-1),
      respectively. Cytochrome b(558) may be the rabbit Dcytb homologue. A novel
      mechanism of how cytochrome b(558) could shuttle electrons from cytoplasmic
      ascorbate to luminal dehydroascorbate is proposed.

PMID- 11846395
TI  - IFN-gamma inhibition of TRAIL-induced IAP-2 upregulation, a possible mechanism of
      IFN-gamma-enhanced TRAIL-induced apoptosis.
AB  - Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a type
      II transmembrane cytokine molecule of TNF family and a potent inducer of
      apoptosis. The anticancer activities of TNF family members are often modulated by
      interferon (IFN)-gamma. Thus, we investigated whether IFN-gamma enhances TRAIL
      induced apoptosis. We exposed HeLa cells to IFN-gamma for 12 h and then treated
      with recombinant TRAIL protein. No apoptosis was induced in cells pretreated with
      IFN-gamma, and TRAIL induced 25% cell death after 3 h treatment. In HeLa cells
      pretreated with IFN-gamma, TRAIL induced cell death to more than 70% at 3 h,
      indicating that IFN-gamma pretreatment sensitized HeLa cells to TRAIL-induced
      apoptosis. We investigated molecules that might be regulated by IFN-gamma
      pretreatment that would affect TRAIL-induced apoptosis. Western blotting analyses
      demonstrated that TRAIL treatment increased the level of IAP-2 protein and IFN
      gamma pretreatment inhibited the upregulation of IAP-2 protein by TRAIL protein.
      Our data indicate that TRAIL can signal to activate both apoptosis induction and
      antiapoptotic mechanism, at least, through IAP-2 simultaneously. IFN-gamma or
      TRAIL treatment alone did not change expression of other pro- or antiapoptotic
      proteins such as DR4, DR5, FADD, Bax, IAP-1, XIAP, Bcl-2, and Bcl-XL. Our
      findings suggest that IFN-gamma may sensitize HeLa cells to TRAIL-induced
      apoptosis by preventing TRAIL-induced IAP-2 upregulation, and IFN-gamma may play
      a role in anticancer therapy of TRAIL protein through such mechanism.

PMID- 11846396
TI  - Mechanisms of L-selectin-induced activation of the nuclear factor of activated T
      lymphocytes (NFAT).
AB  - Selectins are mediating transient contacts of leukocytes with endothelium during
      inflammatory processes and in the development of the immune system. L-selectin
      expressed on almost all leukocytes also functions as a signaling receptor.
      Recently, we have identified different signaling pathways in T lymphocytes by L
      selectin. One signaling cascade leads via the tyrosine kinase p56lck to the small
      G-proteins Ras and Rac and to MAP-kinases. A second independent pathway results
      in ceramide release. In this study, an L-selectin-induced translocation of the
      transcription factor NFAT to the nucleus was identified. Using genetically
      modified JCaM1.6 cells, pharmacological inhibitors, and antisense molecules, it
      was shown that L-selectin-induced NFAT activation depends on src-tyrosine
      kinases, calcineurin and small G-proteins. MAP-kinases and actin filaments were
      identified as Ras effectors involved in NFAT translocation. We conclude that L
      selectin cross-linking results in activation of NFAT by different signaling
      pathways. The activation of NFAT might modulate the immune response of leukocytes
      interacting with endothelial cells.

PMID- 11846397
TI  - Alternative transcripts of a polyhomeotic gene homolog are expressed in distinct
      regions of somites during segmentation of zebrafish embryos.
AB  - Here we describe isolation and characterization of two zebrafish cDNAs,
      designated ph2alpha and ph2beta, which were identified as structural homologs of
      the Drosophila polyhomeotic, mouse Mph2, and human HPH2 genes, collectively
      termed the Polycomb group. The alpha and beta transcripts shared a 1.9-kb
      sequence at their 3'-termini. Alpha had an additional 1.6-kb sequence extending
      toward its 5'-terminus. Only a short 0.1-kb segment was unique to beta.
      Sequencing of a genomic clone corresponding to the two cDNAs indicated that the
      mRNAs were transcribed from a single gene locus by alternative promoters.
      Northern blots revealed expression of alpha transcripts during the segmentation
      period, while beta expression occurred at all developmental stages examined.
      Whole-mount in situ hybridizations with an alpha-specific probe and a probe
      recognizing both transcripts revealed distinct spatio-temporal expression
      patterns along developing somites. Alpha transcripts were detected initially at
      the 7-8 somite stage; beta transcripts appeared in the first somites. As
      segmentation proceeded, alpha and beta expression shifted position toward the
      tailbud in parallel with the formation of each somite. Within individual somites,
      the signal corresponding to alpha was strongest at the posterior border and
      weakest in the anterior region. Conversely, that corresponding to beta was
      strongest at the anterior border and weakest in the posterior region. The data
      support the idea that Ph2alpha and Ph2beta are involved in spatio-temporal
      generation of somites as well as in specification of antero-posterior regional
      differences within individual somites.

PMID- 11846398
TI  - Abnormal expression of neuronal nitric oxide synthase triggers limbic seizures
      and hippocampal damage in rat.
AB  - Administration of tacrine (5 mg/kg ip), an anticholinesterase agent, in rats
      pretreated (24 h beforehand) with lithium chloride (LiCl; 12 mEq/kg ip) provides
      a useful experimental model to study limbic seizures and delayed hippocampal
      damage. Here we report Western blotting evidence demonstrating that in rat LiCl
      and tacrine enhance the expression of neuronal nitric oxide synthase (nNOS), but
      not eNOS, enzyme protein in the hippocampus during the preconvulsive period and
      this triggers seizures and hippocampal damage. In fact, systemic administration
      of 7-nitro indazole (7-NI; 50 mg/kg given ip 30 min before tacrine), a selective
      inhibitor of nNOS, prevented the expression of motor and electrocortical (ECoG)
      seizures and abolished neuronal cell death in the hippocampus. A lower dose (5
      mg/kg ip) of 7-NI was ineffective. In conclusion, the present data support a role
      for abnormal nNOS expression in the mechanism which triggers limbic seizures and
      delayed excitotoxic damage in the hippocampus of rat.

PMID- 11846399
TI  - Paracrine repercussions of preconditioning on angiogenesis and apoptosis of
      endothelial cells.
AB  - The mechanisms of cytoprotection conferred by stress preconditioning remain
      largely uncharacterized in endothelial cells (EC). We report that stress
      preconditioning of EC with serum starvation induces the release of soluble
      mediator(s) that confer resistance to apoptosis, increase proliferation, and
      enhance angiogenesis in a second set of "non-preconditioned" EC. Preconditioning
      was found to target specifically the mitochondrial control of apoptosis in EC
      with increased protein levels of Bcl-2, decreased protein levels of Bax, and
      decreased cytosolic release of cytochrome c. Regulators of apoptosis acting
      upstream and downstream of the mitochondria such as p53, cIAP-1, cIAP-2, and XIAP
      were not altered. Mediators classically associated with preconditioning in other
      cell types such as adenosine, opioids, and nitric oxide are not implicated in
      this cytoprotective loop. Blockade of protein kinase C-dependent signaling
      inhibited cytoprotection of EC. Further characterization of this paracrine
      pathway should provide insights into the molecular regulation of preconditioning
      in endothelial cells.

PMID- 11846400
TI  - Transcriptional regulation of the rat Mrp3 promoter in intestine cells.
AB  - The promoter of rat multidrug resistance protein 3 (Mrp3) has been cloned and
      analyzed in the rat intestinal cell line (IEC-18 cells). A series of 5' deletion
      mutants of the Mrp3 promoter region were constructed and placed into the pGL3
      Basic vector (luciferase reporter gene). Deletion analysis of the Mrp3 promoter
      identified a basal transcription element at -123/-106, two negative response
      regions at -2723/-1128 and -530/-443, respectively, and two positive response
      regions at -1063/-943 and -302/-157. Further site-directed mutagenesis analysis
      and gel mobility shift assays provided evidence for Sp1 and Sp3 binding within 
      123/-105 regions. These studies indicate that Sp1 and Sp3 may be involved in the
      regulation of the rat Mrp3 gene.

PMID- 11846401
TI  - A single amino acid mutation results in a rapid inactivation of epithelial
      calcium channels.
AB  - Epithelial Ca(2+) channel (ECaC1 and 2 = CAT1) molecules are characterized by
      properties including inward rectification and Ca(2+)-dependent fast and slow
      inactivation. To elucidate the electrophysiological differences based on the
      amino acid residues, we compared human and rodent ECaC1, and ECaC2 alignments,
      made mutants, and investigated their function in Xenopus and mammalian cells.
      Expression of the ECaC1 mutant Q579H and a H587Q mutation in ECaC2 in Xenopus
      oocytes resulted in a possible change in the rate of fast decay. Currents of
      H587C and H587N were not detected, and the H587R diminished the rate of rapid
      decay. Treatment of the oocytes with BAPTA magnified the amplitude of the current
      and abolished the decay. The expressions of mutants, therefore, implied that H587
      in ECaC2 is a position related to the mechanism of the rapid decay rather than
      the magnitude of the current or the slow decay. Decay measurements were carefully
      performed in mammalian cells by tight-seal patch clamping. The rapid decay was
      exaggerated in H587C and H587N mutants but was undetectable in the H587R mutant.
      The results indicate that the amino acid 579Q of ECaC1, corresponding to 587H of
      ECaC2, is of primary importance in the structure for the fast inactivation by
      intracellular Ca(2+).

PMID- 11846402
TI  - Characterization of a novel testicular form of human hormone-sensitive lipase.
AB  - Hormone-sensitive lipase (HSL) is an esterase and lipase, which are essential for
      spermatogenesis. Two HSL mRNAs are expressed in human testis. A long form is
      encoded by a testis-specific exon and nine exons common to testis and adipocyte
      HSL. Here we show that the short-form 3.3-kb mRNA possesses a unique 5' end that
      is transcribed from a novel testis-specific exon. The corresponding protein is
      similar to the 775-amino-acid-long adipocyte HSL. Immunohistochemistry
      experiments on human testis sections revealed that the long form is strictly
      expressed in haploid germ cells whereas the short form is expressed in
      interstitial and tubular somatic cells as well as premeiotic germ cells.

PMID- 11846404
TI  - DAP12 ITAM motif regulates differentiation and apoptosis in M1 leukemia cells.
AB  - DAP12 is an immunoreceptor tyrosine-based activation motif (ITAM)-bearing
      transmembrane adapter molecule that is associated with the NK-activating
      receptors. DAP12 is expressed not only in NK cells, but also in myeloid cells.
      Previously, we reported that DAP12 was likely to be involved in monocyte
      differentiation to macrophage. In this study, we established the mutant DAP12-M1
      transfectants (Y76F-M1) that have mutation at their ITAM motifs. We observed that
      Y76F-M1 cells could not differentiate to macrophages by stimulation via DAP12,
      whereas wild type DAP12 transfectants (FDAP-M1) could. Furthermore, we
      demonstrated that the apoptosis signal mediated by LPS was inhibited in Y76F-M1
      cells, but was augmented in FDAP-M1 cells. In contrast to the LPS-mediated
      apoptosis, the combination of LPS and DAP12 stimulation showed good cell
      viability in FDAP-M1 cells. Collectively our studies demonstrated that DAP12 has
      a critical role for macrophage differentiation and LPS induced apoptosis in M1
      leukemia cells.

PMID- 11846403
TI  - Transport of D-serine via the amino acid transporter ATB(0,+) expressed in the
      colon.
AB  - D-Serine, synthesized endogenously in the brain, is an important modulator of
      glutamatergic neurotransmission. Since colonic bacteria produce D-serine, we
      asked the question whether there are transport mechanisms in the colon that might
      make this exogenously produced D-serine available to the host. Here we identify
      for the first time an amino acid transporter in the intestine for high-affinity
      active transport of D-serine. This transporter, called ATB(0,+), is a Na(+)- and
      Cl(-)-coupled transporter for L-enantiomers of neutral and cationic amino acids.
      Here we demonstrate that ATB(0,+) is also capable of mediating the Na(+)- and Cl(
      )-coupled transport of D-serine. The affinity of ATB(0,+) for L-serine and D
      serine is similar, the K(t) value for the two enantiomers being approximately 150
      microM. In addition to D-serine, ATB(0,+) transports D-alanine, D-methionine, D
      leucine, and D-tryptophan. However, several other neutral and cationic amino
      acids that are transportable substrates for ATB(0,+) as L-enantiomers are not
      transported when presented as D-enantiomers. ATB(0,+) is expressed in the
      intestinal tract, interestingly not in the proximal intestine but in the distal
      intestine. Expression is most predominant in the colon where the transporter is
      localized to the luminal membrane of colonocytes, making this transporter
      uniquely suitable for absorption of bacteria-derived D-serine.

PMID- 11846405
TI  - Functional redundancy in the myotubularin family.
AB  - Myotubularin-related genes define a novel highly conserved family of eukaryotic
      proteins of at least 11 human members. The hMTM1 gene that codes for myotubularin
      is mutated in X-linked myotubular myopathy, a severe congenital disease.
      Recently, we and others have characterized myotubularin as a potent and specific
      phosphatidylinositol 3-phosphate 3-phosphatase. In the present study we
      investigated the lipid phosphatase activity and the subcellular localization of
      two other members of the family, hMTMR2 protein that is mutated in the
      demyelinating neuropathy Charcot-Marie-Tooth type 4B and the FYVE-finger
      containing hMTMR3 protein. Our results show that both proteins are potent
      phosphatidylinositol 3-phosphate 3-phosphatases either in vitro or in yeast where
      they interfered with vesicular trafficking. Their localization is mainly
      cytoplasmic, with however strong labeling of Rac-inducible plasma membrane
      ruffles. The fact that the ubiquitously expressed hMTM1 and hMTMR2 genes are
      involved in different pathologies indicates that despite their shared enzymatic
      activity, they are not functionally redundant, at least in certain cell types.
      This might be explained by subtle differences in expression and/or in recruitment
      and regulation at their specific site of action.

PMID- 11846406
TI  - Cloning and functional expression of the first Drosophila melanogaster sulfakinin
      receptor DSK-R1.
AB  - Described in this report is a successful cloning and characterization of a
      functionally active Drosophila sulfakinin receptor designated DSK-R1. When
      expressed in mammalian cells, DSK-R1 was activated by a sulfated, Met(7-->Leu(7)
      substituted analog of drosulfakinin-1, FDDY(SO(3)H)GHLRF-NH(2) ([Leu(7)]-DSK-1S).
      The interaction of [Leu(7)]-DSK-1S with DSK-R1 led to a dose-dependent
      intracellular calcium increase with an EC(50) in the low nanomolar range. The
      observed Ca(2+) signal predominantly resulted from activation of pertussis toxin
      (PTX)-insensitive signaling pathways pointing most likely to G(q/11) involvement
      in coupling to the activated receptor. The unsulfated [Leu(7)]-DSK-1 was ca. 3000
      fold less potent than its sulfated counterpart which stresses the importance of
      the sulfate moiety for the biological activity of drosulfakinin. The DSK-R1 was
      specific for the insect sulfakinin since two related vertebrate sulfated
      peptides, human CCK-8 and gastrin-II, were found inactive when tested at
      concentrations up to 10(-5) M. To our knowledge, the cloned DSK-R1 receptor is
      the first functionally active Drosophila sulfakinin receptor reported to date.

PMID- 11846407
TI  - Calpain activation after mitochondrial permeability transition in microcystin
      induced cell death in rat hepatocytes.
AB  - Previous studies have shown that microcystin-LR (MLR), a specific hepatotoxin,
      induces onset of mitochondrial permeability transition (MPT) and apoptosis in
      cultured rat hepatocytes. Here we attempted to investigate the downstream events
      after the onset of MPT in MLR-treated hepatocytes. Various mitochondrial electron
      transport chain (ETC) inhibitors effectively prevented the onset of MPT,
      suggesting that the mitochondrial ETC plays an important role in MLR-induced MPT.
      MLR also induced mitochondrial cytochrome c release, which can be prevented by a
      specific MPT inhibitor (cyclosporin A, CsA), and by various ETC inhibitors.
      Interestingly, the release of cytochrome c did not activate caspase-9 and -3, the
      main caspases involved in apoptosis. Instead, MLR activated calpain in rat
      hepatocytes, probably through the increase of intracellular Ca(2+) released from
      mitochondria. Both ALLN and ALLM, two calpain inhibitors, significantly blocked
      MLR-induced calpain activation and subsequent cell death. CsA also prevented MLR
      induced calpain activation and cell death, suggesting that the activation of
      calpain may be a post-mitochondrial event. These data demonstrate for the first
      time that calpain rather than caspases plays an important role in MLR-induced
      apoptosis.

PMID- 11846408
TI  - Lack of contribution of mitochondrial electron transport to acute O(2) sensing in
      model airway chemoreceptors.
AB  - We have recently reported that the model airway chemoreceptors, H146 cells,
      exhibit a significant component of their oxygen-sensing transduction pathway
      which cannot be explained by activity of NADPH oxidase. Using patch-clamp, we
      have studied the transduction system linking reduced O(2) to k(+) channel
      inhibition and report that, in complete contrast to recent suggestions in
      pulmonary vasculature, O(2) sensing by the model airway chemoreceptors, H146
      cells, does not require functional mitochondria. These data show, for the first
      time, that mitochondrial production of reactive O(2) species is not the unifying
      mechanism in O(2) sensing.

PMID- 11846409
TI  - Mutation in the Xanthomonas campestris xanA gene required for synthesis of
      xanthan and lipopolysaccharide drastically reduces the efficiency of
      bacteriophage (phi)L7 adsorption.
AB  - (Phi)L7 is a lytic phage infecting the gram-negative Xanthomonas campestis pv.
      campestris, a plant pathogen. To study phage-host interaction, a (phi)L7
      resistant mutant was isolated from strain Xc17 by mini-Tn5 transposition and
      designated CH7LR. CH7LR could not plate (phi)L7 in double-layered assay and
      formed turbid clearing zones when the cell lawn was dropped with a high titer of
      (phi)L7. Sequence analysis showed that the mutated gene is xanA coding for
      phosphoglucomutase/phosphomannomutase, required for the synthesis of
      lipopolysaccharide and exopolysaccharide (xanthan). The involvement of xanA was
      confirmed by isolating another mutant with interrupted xanA and complementing
      with the cloned wild-type gene. Nonmucoid mutants are still sensitive to (phi)L7,
      indicating that xanthan is not involved in (phi)L7 adsorption. Since the mutants
      still exhibited low efficiencies of phage adsorption, we predict, by analogy with
      the cases in other bacteriophages of gram-negative bacteria, that other outer
      membrane components such as a protein are required for the formation of a complex
      receptor.

PMID- 11846410
TI  - Simultaneous detection of thiamine and its phosphate esters from microalgae by
      HPLC.
AB  - We present an easy and sensitive method for measuring thiamine and its phosphate
      esters in small biological samples of microalgae (Amphidinium carterae Hulburt
      and Nitzschia microcephala Grun). The method consists of extraction of thiamine
      and its derivatives in acid solution, followed by liquid chromatography with
      fluorescence detection. The detection limit is as low as 15 fmol of thiamine. For
      comparison to microalgae, the method has been applied to evaluate thiamine levels
      in the crustacean Artemia salina Leach and is suitable for nutritional studies of
      the food web of the Baltic salmon, which suffers from thiamine deficiency. This
      method of HPLC analysis can be readily utilized to follow uptake and
      interconversion of thiamine and its phosphate esters in many micro- and
      macroalgae.

PMID- 11846411
TI  - Mixed tocopherol preparation is superior to alpha-tocopherol alone against
      hypoxia-reoxygenation injury.
AB  - Hypoxia-reoxygenation (H-R) is associated with alterations in oxidant-antioxidant
      balance and L-arginine-nitric oxide system. Tocopherols decrease the activity of
      reactive oxygen species (ROS) and yet are not beneficial in clinical trials. It
      has been proposed that mixed tocopherols as found in nature may be more tissue
      protective than alpha-tocopherol alone found in commercial preparations. We
      compared the effect of a mixed tocopherol preparation with that of alpha
      tocopherol alone on superoxide dismutase (SOD) activity and iNOS expression in
      cultured myocytes exposed to H-R. Myocytes from Sprague-Dawley rat hearts were
      subjected to hypoxia for 24 h followed by reoxygenation for 3 h H-R. Parallel
      groups of myocytes were pretreated with alpha-tocopherol alone or a mixed
      tocopherol preparation (containing alpha-, gamma-, and delta-tocopherols) (50
      microM) for 30 min. H-R resulted in myocyte injury (determined by LDH release), a
      decrease in SOD activity and an upregulation of iNOS expression/activity. Both
      tocopherol preparations attenuated cell injury and markedly decreased the effects
      of H-R on SOD activity and iNOS expression/activity (all P < 0.05 vs H-R group, n
      = 5). However, mixed-tocopherol preparation was much superior to alpha-tocopherol
      in terms of myocyte protection from the adverse effect of H-R (P < 0.05). Lack of
      efficacy of commercial tocopherol preparations in clinical trials may reflect
      absence of gamma- and delta-tocopherols.

PMID- 11846412
TI  - Terpenoids found in the umbelliferae family act as agonists/antagonists for
      ER(alpha) and ERbeta: differential transcription activity between ferutinine
      liganded ER(alpha) and ERbeta.
AB  - Phytoestrogens are assumed to affect the endocrine system of animal species
      similarly to other man-made endocrine disrupters and to exert their effects
      through estrogen receptors, specifically ER(alpha) and ERbeta. However, these
      molecular mechanisms are not fully understood. In this study, 19 phytochemicals
      were surveyed for agonist and antagonist activities of ER(alpha) and ERbeta using
      an ERE-luciferase reporter assay. The results showed that ferutinine is an
      agonist for ER(alpha) and an agonist/antagonist for ERbeta, tschimgine is an
      agonist for both ER(alpha) and ERbeta, and tschimganidine is an agonist for only
      ER(alpha). Ferutinine and tschimganidine are sesquiterpenoids, and tschimgine is
      a monoterpenoid derived from the Umbelliferae family. A competitive binding assay
      showed that ferutinine has higher binding affinities than tamoxifen for both ERs.
      Co-transfections of coactivators such as SRC-1, TIF2, AIB1, and TRAP220 in 293T
      cells and use of the luciferase assay revealed that TRAP220 failed to enhance the
      transcription mediated by ERbeta in the presence of ferutinine. Moreover, a GST
      pull-down assay showed that TRAP220 marginally bound to ERbeta ligand binding
      domain in the presence of ferutinine. These results suggest that the conformation
      of ferutinine-liganded ERbeta is difficult for TRAP220 to recognize. Taken
      together, this suggests that some terpenoids can modulate estrogen signaling as
      ER subtype-selective phytoestrogens similar to SERMs (selective estrogen receptor
      modulators).

PMID- 11846413
TI  - Direct atomic force microscopy visualization of integration host factor-induced
      DNA bending structure of the promoter regulatory region on the Pseudomonas TOL
      plasmid.
AB  - Atomic force microscopy (AFM) was used to analyze DNA bending induced by
      integration host factor (IHF). The direct AFM visualization of IHF-DNA complexes
      on the OP1 promoter regulatory regions on the Pseudomonas TOL plasmid showed that
      there was no intrinsic DNA bend in the OP1 promoter region, but a sharp DNA bend
      was induced by binding of IHF to the region between the upstream regulatory
      sequence and the promoter sequence. The DNA bending angles were distributed with
      a mean bend angle of 123 degrees. The IHF-DNA complexes were shown to bend at the
      IHF binding site giving rise to an asymmetric structure. These results provide
      direct evidence that IHF is required functionally for activation of OP1
      transcription and support the DNA-loop model that the sharp DNA bend induced by
      binding of IHF facilitates the contact between RNA polymerase bound by the
      promoter sequence and XylR protein attached to the upstream sequence in the OP1
      promoter.

PMID- 11846414
TI  - Positively charged DNA-binding proteins cause apparent cell membrane
      translocation.
AB  - Several positively charged DNA-binding proteins such as the human
      immunodeficiency virus Tat protein, the Antennapedia (Antp) homeobox protein, and
      the herpes simplex virus VP22 protein have been reported to translocate across
      cell membranes and accumulate in cell nuclei. The import occurs by a poorly
      understood mechanism that appears to be receptor- and energy-independent. We
      showed that both VP22 and the positively charged histone H1 adhered to the cell
      membrane of living cells and were not removed by extensive washing. However,
      after fixation the proteins relocated to the cell nucleus. The nuclear
      accumulation of VP22 and histone H1 after fixation shows that positively charged
      proteins may appear to translocate across the cell membrane because of a fixation
      artifact. The majority of studies on "membrane permeable" proteins and peptides
      have been performed using fixation techniques, and our study shows that influx of
      these proteins may occur during fixation rather than in living cells.

PMID- 11846415
TI  - Ablation of cellular prion protein expression affects mitochondrial numbers and
      morphology.
AB  - The cellular prion protein (PrP(C)), predominantly expressed in the central
      nervous system, is required for pathogenesis of prion neurodegenerative diseases
      and its conversion into a pathogenic isoform (PrP(Sc)) is a common feature of
      disease. While the physiological function of PrP(C) remains unclear, accumulating
      evidence indicates a role for PrP(C) in oxidative homeostasis in vivo and
      suggests that PrP(C) may be involved in the cellular response to oxidative
      stress. Mice in which PrP(C) expression has been ablated are viable and develop
      normally. Here we show that in an inbred line of mice, in tissues that normally
      express PrP at moderate to high levels, ablation of PrP(C) results in reduced
      mitochondrial numbers, unusual mitochondrial morphology, and elevated levels of
      mitochondrial manganese-dependent superoxide dismutase antioxidant enzyme. These
      observations may have relevance to the pathogenic mechanism for this group of
      fatal neurodegenerative conditions.

PMID- 11846416
TI  - A Link between cholesterol levels and phenobarbital induction of cytochromes
      P450.
AB  - Squalestatin1 (SQ1), a potent inhibitor of squalene synthase produced a dose
      dependent induction of cytochromes P450 CYP2H1 and CYP3A37 mRNAs in chicken
      hepatoma cells. The effect of SQ1 was completely reversed by 25
      hydroxycholesterol. Bile acids elicited an induction of CYP3A37 and CYP2H1 mRNA.
      Bile acids also reduced the phenobarbital induction of CYP2H1 but not of CYP3A37
      mRNA. The effects of SQ1 and its reversal by 25-hydroxycholesterol and the
      effects of bile acids were reproduced in reporter gene assays with a
      phenobarbital-responsive enhancer unit of CYP2H1. These data suggest that an
      endogenous molecule related to cholesterol homeostasis regulates induction of
      drug-inducible CYPs.

PMID- 11846417
TI  - Titin mutations as the molecular basis for dilated cardiomyopathy.
AB  - Dilated cardiomyopathy (DCM) is a heterogeneous cardiac disease characterized by
      ventricular dilatation and systolic dysfunction. Recent genetic studies have
      revealed that mutations in genes for cardiac sarcomere components lead to DCM.
      The cardiac sarcomere consists of thick and thin filaments and a giant protein,
      titin. Because one of the loci of familial DCM was mapped to the region of the
      titin gene, we searched for titin mutations in the patients and identified four
      possible disease-associated mutations. Two mutations, Val54Met and Ala743Val,
      were found in the Z-line region of titin and decreased binding affinities of
      titin to Z-line proteins T-cap/telethonin and alpha-actinin, respectively, in
      yeast two-hybrid assays. The other two mutations were found in the cardiac
      specific N2-B region of titin and one of them was a nonsense mutation,
      Glu4053ter, presumably encoding for a truncated nonfunctional molecule. These
      observations suggest that titin mutations may cause DCM in a subset of the
      patients.

PMID- 11846419
TI  - Cloning and expression of a full-length cDNA encoding human inositol 1,4,5
      trisphosphate 3-kinase B.
AB  - Inositol 1,4,5-trisphosphate (InsP(3)) 3-kinase catalyzes the phosphorylation of
      InsP(3) to inositol 1,3,4,5-tetrakisphosphate (InsP(4)). cDNAs encoding three
      isoenzymes of InsP(3) 3-kinase (3-kinases A, B, and C) have been previously
      reported; however, a demonstrably full-length cDNA encoding human InsP(3) 3
      kinase B was still lacking. Here we report the cloning of a full-length 2841-bp
      cDNA encoding human InsP(3) 3-kinase B. Northern blot analysis shows the presence
      of an ubiquitous transcript of approximately 7.2 kb in a large number of human
      tissues. InsP(3) 3-kinase activity measured in COS-7 cells transfected with
      InsP(3) 3-kinase B shows an activity that was 8-fold increased upon the addition
      of Ca(2+)/calmodulin in the assay mixture.

PMID- 11846418
TI  - Insulin stimulates nitric oxide production in rat adipocytes.
AB  - In adipocytes, insulin regulates the activity of different protein kinases
      (PI3K/Akt, MAPK, PKC) and protein phosphatases (PP-1, PP-2A). Since these enzymes
      are implicated in the regulation of NOS activity which is present in adipose
      tissue, we tested the effects of insulin on white adipocyte NOS activity.
      Exposure of adipocytes to insulin resulted simultaneously in NOS activity
      stimulation and Akt activation with maximal effect observed at 1 nM. Higher
      concentrations of insulin induced a progressive decline of NOS activity. In the
      presence of wortmannin, a PI3K inhibitor, 1 nM insulin failed to stimulate NOS
      activity. Insulin (1 nM)-stimulated NOS activity was also abolished by U0126, an
      inhibitor of p42/p44 MAPK activation, and by 1 microM okadaic acid (OA), which
      inhibits both PP-1 and PP-2A but not by 1 nM OA which inhibits only PP-2A.
      Moreover, inhibition of cPKC allowed a high (1 microM) insulin concentration to
      stimulate NOS activity. These results (i) demonstrate that insulin activates NO
      production in adipocytes through both PI3K/Akt and MAPK/PP-1 activation and (ii)
      suggest that PP-1 activation protects NOS against the inhibitory effect of cPKC
      activation.

PMID- 11846420
TI  - Molecular cloning, gene localization, and structure of human cyclin B3.
AB  - Here we describe the molecular cloning of human cyclin B3, its localization, and
      its structure. It is localized in the subcentromeric region of the X chromosome,
      still not completely sequenced by the Human Genome Project. This cyclin B3 is
      unusually large for a mitotic cyclin. Its mRNAs were found in all tissues and
      were particularly abundant in testis. At least three splice variants were found
      in the ORF and three variants in the 5'UTR.

PMID- 11846421
TI  - Cloning, characterization, and expression of calcyphosine 2, a novel human gene
      encoding an EF-hand Ca(2+)-binding protein.
AB  - Calcyphosine is a calcium-binding protein containing four EF-hand domains,
      initially identified as thyroid protein p24. It was first cloned and its
      counterparts in rabbit, human, and mouse, crayfish and lobster of invertebrate
      were also cloned. Here we describe the cloning and characterization of a novel
      human calcyphosine gene. The 3829-bp cDNA encodes a EF-hand Ca(2+)-binding
      protein homologous to the dog calcyphosine. It also contains two EF-hand Ca(2+)
      binding motif. It is abundantly expressed in many tissues including by RT-PCR
      analysis and believed to play important role in calcium signaling. It was mapped
      to human genome 12q15.

PMID- 11846422
TI  - Activation by acidic pH of CLC-7 expressed in oocytes from Xenopus laevis.
AB  - ClC chloride channels are important in diverse physiological functions such as
      transepithelial transport, cell volume regulation, excitability, and
      acidification of intracellular organelles. We have investigated the expression of
      CLC-7 in oocytes from Xenopus laevis with the two electrode voltage clamp
      technique and Western blot analysis. Using a specific antibody against CLC-7, we
      found an approximately 80 kDa protein in oocytes, previously injected with CLC-7
      cRNA. In voltage clamp experiments on ClC-7-cRNA-injected oocytes, no current
      changes were detected at normal pH (7.4). However, acidification of the Ringer
      solution to pH values between 6 and 4 revealed strong currents which reversed at
      about -15 mV (30 mV positive to the normal resting potential) and showed strong
      outward rectification. We therefore suggest that ClC-7 in oocytes is a functional
      chloride current at acidic pH. Since ClC-7 is also found in neuronal tissues and
      was upregulated in a rat pain model, we suggest a role of CLC-7 also for
      nociception and pain.

PMID- 11846423
TI  - Activity enhancement of Cel5Z from Pectobacterium chrysanthemi PY35 by removing C
      terminal region.
AB  - The phytopathogenic bacterium Pectobacteium chrysanthemi PY35 secretes Cel5Z
      endoglucanase belonging to the glycoside hydrolase family 5 of EC 3.2.1.4. The
      mutation of cel5Z::Omega gene was constructed by cloning the 2.0-kb SmaI fragment
      containing the streptomycin/spectinomycin-resistance gene of pHP45(Omega) into
      the BalI site of pPY100. The insertion of Omega fragment generated a new stop
      codon, removing the Ser/Thr-rich linker region and the cellulose binding domain
      (CBD) in the C-terminal region of cel5Z gene. By subsequent subcloning from this
      4.9-kb fragment (pPY1001), a 1.0-kb (pPY1002) fragment was obtained and
      designated as cel5Z::Omega. The cel5Z::Omega gene had an open reading frame (ORF)
      of 1011 bp, encoding 336 amino acids, starting with an ATG codon and ending with
      a new TGA stop codon. The molecular mass of the Cel5Z::Omega protein in E. coli
      transformant appeared to be 32 kDa by SDS-PAGE analysis in the presence of
      carboxymethyl-cellulose (CMC). The Cel5Z::Omega protein hydrolyzed CMC with 1.7
      fold higher activity than the intact Cel5Z cellulase.

PMID- 11846425
TI  - Quantification of lipopolysaccharides in outer membrane vesicle vaccines against
      meningococcal disease. High-performance liquid chromatographic determination of
      the constituent 3-hydroxy-lauric acid.
AB  - A high-performance liquid chromatographic (HPLC) assay for quantification of
      lipopolysaccharides (LPSs, endotoxins) in outer membrane vesicle vaccines against
      meningococcal disease has been developed. The LPS constituent, 3-hydroxy-lauric
      acid, served as marker substance for the quantification. LPS from the vaccine was
      precipitated by ethanol and the fatty acid constituents, including 3-hydroxy
      lauric acid, were released by acidic hydrolysis, collected and purified by solid
      phase extraction on C18 disc-cartridges and converted into phenacyl esters for UV
      detection at 240 nm. Quantification of the derivatized 3-hydroxy-lauric acid was
      achieved by HPLC using a Brownlee RP-18 reversed phase column with
      acetonitrile/water (68:32, v/v) as mobile phase. The method was found to be
      linear over the range 3-49 microg LPS/ml with a sensitivity of 1.6 (microg/ml)(
      1). The repeatability (within-day precision) of the method at three levels (3-49
      microg LPS/ml) was 6-14% relative standard deviation and the intermediate
      (between-day) precision was 7% relative standard deviation (at level 15 microg
      LPS/ml). The method has been successfully used in the quality control of a
      meningococcal B outer membrane vesicle vaccine, containing 4-8% LPS relative to
      protein (w/w), in our laboratory for three years.

PMID- 11846424
TI  - Presence of cytokines in biological preparations.
AB  - In vaccines produced in eukaryote cells as well as in commercial medical
      preparations of leukocyte interferon a number of cytokines such as IL-1beta, IL-6
      and TNF-alpha have been detected. Among the vaccines examined in this study the
      highest level of IL-1beta was demonstrated in inactivated hepatitis A vaccine
      prepared in the green monkey kidney cell line 4647, that of IL-6 in inactivated
      rabies vaccine produced in Syrian hamster kidney (SHK) cell culture, and that of
      TNF-alpha in live poliomyelitis vaccine manufactured in VERO cells. A spontaneous
      and poliovirus-induced capacity of cell cultures to produce cytokines was
      detected. The level of cytokines produced depend on the kind of cell culture and
      the type of virus, a more pronounced effect being generated by types 1 and 2
      poliovirus as compared with type 3. The presence of highly active cytokines in
      virus vaccines and interferon preparations points to the necessity of
      investigating the influence of the presence of cytokines on the biological
      activity of these preparations and to the advisability of standardizing and
      controlling the cytokine content.

PMID- 11846426
TI  - Evaluation of a quantitative product-enhanced reverse transcriptase assay to
      monitor retrovirus in mAb cell-culture.
AB  - Murine hybridoma cells used in the production of monoclonal antibodies (mAbs)
      produce endogenous type C retrovirus particles. Regulatory agencies require a
      demonstration that mAbs intended for human use are free of retrovirus with an
      adequate margin of safety. This is usually achieved by evaluation studies,
      performed at small scale, to demonstrate that the manufacturing process is
      capable of removing or inactivating several different model viruses, including a
      murine retrovirus. In a previous report, we demonstrated the utility of TaqMan
      fluorogenic 5'-nuclease product-enhanced reverse transcriptase (TM-PERT) assays
      for measuring reverse transcriptase (RT) activity in laboratory-scale cell
      culture samples and RT removal by laboratory-scale models of processing steps. In
      this report, we evaluate the specificity, accuracy, range, precision and
      robustness of TM-PERT for this purpose. We find that this assay detects RT
      activity contained in xenotropic murine leukemia virus (X-MuLV) and CHO cell type
      C particles and quantifies particle numbers comparably to other assays (e.g.
      transmission electron microscopy, viral sequence specific TaqMan). Cell derived
      DNA polymerases appear to contribute only modestly to the assay background and RT
      activity in clarified cell culture harvests is contained largely in Type C
      particles. TM-PERT is linear and precise between 10(7)and 10(13) pU/ml,
      establishing the assay range. The assay is robust in that test article storage
      condition and DNA/protein content had little impact on assay performance. Thus,
      TM-PERT appears to be an acceptable assay to measure type C particles in rodent
      cell culture samples.

PMID- 11846427
TI  - Method for detection of extraneous active bovine viral diarrhoea virus and
      classical swine fever virus in animal viral vaccines by RT-PCR, which amplify
      negative-strand viral RNA in infected cells.
AB  - An oligonucleotide sense primer, Pst324alpha, was designed and used for
      synthesizing cDNA from negative-strand viral RNA in infected cells and used for
      rapid detection of active extraneous bovine viral diarrhoea virus (BVDV) and
      classical swine fever virus (CSFV) in animal viral vaccines by culturing a sample
      in cells followed by reverse transcriptase-polymerase chain reaction (RT-PCR).
      Active and inactivated viruses of BVDV No. 12-43 strain and CSFV GPE(-)strain
      were inoculated to bovine testicle and swine testicle cells for incubation. After
      the complete extraction of RNA from these cells, cDNA was synthesized using
      Pst324alpha, and PCR was carried out using primers 324 and 326 (novel RT-PCR).
      Amplification of novel RT-PCR products was observed in cells infected with active
      viruses but not in cells inoculated with inactivated viruses, inoculums and
      cultured media after incubation. This novel RT-PCR was able to amplify viral
      sequences from cells infected with only a small number of infectious particles
      (less than 10 TCID50) at three days postinoculation and was as sensitive as the
      general RT-PCR using a random primer and the interference and immunofluorescent
      antibody (FA) methods. The results of experiments on detection of BVDV RNA from
      vaccines contaminated with active and inactivated BVDV showed that the
      sensitivity of the novel RT-PCR was almost the same as the sensitivities of the
      interference and FA methods. These results suggest that the novel RT-PCR is
      easier and more rapid than the interference method for detection of active BVDV
      and that the novel RT-PCR is a reliable means for detection of active extraneous
      BVDV for quality control of animal vaccines.

PMID- 11846428
TI  - An international collaborative study on a method for determination of
      formaldehyde in veterinary vaccines.
AB  - An international collaborative study of a quantitative colorimetric method for
      determination of formaldehyde in veterinary vaccines was conducted on a series of
      replicate, blinded veterinary vaccine products by 15 laboratories in three
      regions: North America, Europe and Japan. Participants conducted determinations
      using a modification of a method from the European Pharmacopoeia, a colorimetric
      method based on the reaction of formaldehyde with methylbenzothiazolone hydrazone
      hydrochloride. For this study, three licensed vaccine products containing
      formaldehyde were revialed, randomly numbered, tested for uniformity and
      distributed by one of the participating laboratories through regional
      coordinators to collaborators. One of the revialed products was spiked with a
      known amount of formaldehyde and included in the test series. Results along with
      all raw data were returned to the distributing laboratory for consolidation and
      statistical treatment. For the modified method spike recovery was 101% and
      reproducibility (inter-laboratory variation expressed as relative standard
      deviation) ranged from 18.0 to 8.0% for respective formaldehyde concentrations of
      0.28 to 1.07 g/l. Based on the study, the method was proposed by the Biologicals
      Working Group of the International Cooperation on Harmonization of Technical
      Requirements for Registration of Veterinary Medicinal Products (VICH) as a
      candidate for the VICH Guideline standard method for residual formaldehyde.

PMID- 11846429
TI  - Report of a collaborative study to assess the suitability of a reference reagent
      for antibodies to hepatitis E virus.
AB  - Several commercial and "in-house" assays have been developed for the detection of
      antibodies to hepatitis E virus, a major causative agent of enterically
      transmitted non-A non-B hepatitis. As these kits contain a variety of synthetic
      peptides or recombinant proteins, greater standardisation is required. A
      collaborative study was therefore carried out to assess the suitability of a
      freeze dried preparation designated 95/584 to serve as a reference reagent for
      hepatitis E virus serum IgG. Preparation 95/584, which is a serum from a
      previously infected individual, was assayed along with four coded samples, one of
      which D, was a coded duplicate of 95/584, and three individual sera, coded A, B
      and C. These preparations were sent to seven laboratories in five countries who
      tested them in eight different enzyme immunoassays. In most laboratories the
      coded duplicate gave a mean potency of within 20% of the candidate reference
      reagent despite the wide range of assays used. However, the potencies of the
      coded samples which were from different individuals gave somewhat variable
      potencies relative to the candidate reference reagent. This is not surprising as
      each sample will have varying proportions of antibodies against individual viral
      proteins and result in the variation in results observed. Nevertheless, this
      material will be of use in the standardisation of diagnostic tests for use in
      sero-prevalence studies and for assessing immunity. Preparation 95/584 was found
      to be suitable to serve as a reference reagent for hepatitis E serum IgG and has
      been established as an interim Reference Reagent for Human anti-hepatitis E
      serum. Each ampoule contains 50 Units per ampoule.

PMID- 11846430
TI  - Calibration of replacement international standard and European pharmacopoeia
      biological reference preparation for tetanus toxoid, adsorbed.
AB  - Here we report the characterisation of a preparation of tetanus toxoid, adsorbed,
      and its calibration by 27 laboratories in 19 countries in a joint international
      collaborative study co-sponsored by World Health Organization (WHO) Expert
      Committee of Biological Standardization (ECBS) and the European Biological
      Standardisation Programme of European Directorate for the Quality of Medicines
      (EDQM), Council of Europe. Calibration was in terms of the Second International
      Standard (I.S.) for Tetanus Toxoid, Adsorbed, by the established WHO/European
      Pharmacopoeia (Ph Eur) challenge methods. The replacement standard preparation
      was found to have a unitage of 469 IU/ampoule on the basis of its calibration in
      guinea-pigs and 496 IU/ampoule on the basis of its calibration in mice.
      Assessment, both within the collaborative study and as part of candidate
      characterisation, indicated satisfactory stability of the candidate preparation.
      This study also provided some information on the effect of mouse strain on
      potency testing of tetanus vaccines. A limited assessment of the impact of the
      replacement standard on testing of current production batches of vaccines was
      also carried out by four manufacturers. This study did not directly address the
      serological approaches to potency testing. However, one laboratory offered data
      from mouse serology assay, which gave comparable estimates to in vivo mouse
      bioassay. Based on the results of this study and with the agreement of
      participants, the candidate standard was established as the Third International
      Standard for Tetanus Toxoid, Adsorbed (coded 98/552) by the WHO Expert Committee
      of Biological Standardization (ECBS) in November 2000. The same preparation was
      also established as the second Ph Eur Biological Reference Preparation (Ph Eur
      BRP, batch no. 2) by the Steering Committee of the Biological Standardisation
      Programme of the EDQM and approved by the European Pharmacopoeia Commission.

PMID- 11846431
TI  - Establishment of a standard assay method for human thrombomodulin and
      determination of the activity of the Japanese reference standard.
AB  - This study was undertaken to establish a standard method for determination of the
      activity of human (h) thrombomodulin (TM). The reactions mainly consisted of
      formation of a h-TM and h-thrombin complex, activation of h-protein C by the
      complex and digestion of substrate by activated h-protein C. Linear time
      dependent formation of p -nitroaniline from the substrate, S-2366, was observed
      up to 12 min during measurement of the activity of urinary h-TM (uh-TM) reference
      material by the standard method. Therefore, 10 minutes was established as the
      reaction time in the standard method. In the standard method, we defined the
      activity of h-TM forming 0.1 micromol of p -nitroaniline per min in the reaction
      as 1 JRS Unit. Recombinant h-TM (rh-TM) and uh-TM reference material gave
      rectilinear dose-response curves within a certain range of specific activities by
      their original methods in the standard method. The validity of the standard
      method was assessed based on the coefficients of variation (CV) obtained in the
      various measurements of h-TM. Intra-batch precision (CV) of h-thrombin and h
      protein C was 2.90% and 6.57%, respectively, in the measurement of uh-TM
      activity. The intra-sample, inter-day, and inter-laboratory precision (CV) was
      1.30%, 1.63% and 5.02%, respectively, in the measurement of the first Japanese
      reference standard for h-TM coded TJRS1. In these assays, the activity of the
      first Japanese standard was also determined and found to be 205 JRS units per
      ampoule. When the stability of the Japanese reference standard was assessed by
      measuring of the standard stored under various thermal conditions, the predicted
      loss of activity assuming monomolecular degradation according to the Arrhenius
      equation was less than 3.0% during 103 years at -20 degrees C. These results
      indicate that the standard method is appropriate for determination of the
      activity of h-TM and that the Japanese reference standard for h-TM, whose
      activity was determined here, can be stored at -20 degrees C for long periods
      without loss of activity.

PMID- 11846432
TI  - Synthesis, anti-HIV activity, and stability studies of 5'-phosphorofluoridate
      derivatives of AZT.
AB  - The synthesis, in vitro anti-HIV activity and stability studies of the 5'
      fluorophosphate derivative of 3'-azido-3'-deoxythymidine (AZT) are reported. The
      results support the hypothesis that this phosphorylated entity exerts its
      biological effect via the delivery of the corresponding 5'-mononucleotide through
      an enzymatic process. However, the antiviral evaluation in thymidine kinase
      deficient CEM cells as well as the stability studies in culture medium and cell
      extract showed that this bioconversion is not specific to the intracellular
      medium. Attempts to improve the biological activity of mononucleoside 5'
      fluorophosphates by the use of the S-pivaloyl-2-thioethyl (tBuSATE) group as
      biolabile phosphate protection are reported.

PMID- 11846433
TI  - Concerning two-metal cooperativity in model phosphate hydrolysis.
AB  - Three series of bimetallic ligands were tested for cooperativity in the
      hydrolysis of phosphate esters. It was shown that rate enhancements were in part
      contributed by binding to the hydrophobic linkers when the substrates were also
      hydrophobic, and two metal cooperativity was not found to be present. Kinetic
      order tests were performed and shown to be superior to previous methods for
      analyzing cooperativity.

PMID- 11846434
TI  - Synthesis of RGD analogs as potential vectors for targeted drug delivery.
AB  - RGD analogs bind to integrin receptors with high affinity and therefore have the
      potential to be used as vectors for the targeted delivery of pharmaceutical
      agents to designated sites. Critical to this application is the ability to
      synthesize RGD analogs with different side chain functional groups that allow for
      the ready tethering of pharmaceutical agents without sacrificing their affinity
      for the target receptor significantly. A series of RGD analogs intended to be
      used as delivery vectors of pharmaceutical agents were prepared and evaluated for
      their ability to inhibit platelet aggregation by binding to glycoprotein
      IIb/IIIa. Among them, compound 11 showed the lowest IC50 against platelets
      activated by ADP. It was found that such RGD analogs could tolerate side chain
      modification fairly well with various functional groups attached such as amide,
      amine, ester, protected amine and poly(ethylene glycol). The fact that the
      compound with a side chain modification of poly(ethylene glycol) retained high
      affinity for glycoprotein IIb/IIIa (IC50 150 nM) suggests the feasibility of
      tethering fairly large pharmaceutical agents to such RGD analogs without
      significant sacrifice of their affinity to the intended receptor.

PMID- 11846435
TI  - Microwave induced synthesis and antibacterial activity of cephalosporin
      derivatives using solid support.
AB  - Reaction of 7-amino-3-[5'-methyl-1',3',4'-thiadiazol-2'-ylthiomethyl]cephalo
      sporanic acid with heterocyclic amines using basic alumina under microwave
      irradiation (MWI) afforded new cephalosporin analogs in shorter reaction time
      with improved yield as compared to conventional heating. All the synthesised
      compounds were tested for their in vitro antibacterial activity, using cefotaxime
      and cephalothin as reference drugs. All compounds showed significant in vitro
      antibacterial activity against E. herbicola, P. vulgaries, and Z. mobilis.

PMID- 11846436
TI  - 4-hydroxy-2-nonylquinoline: a novel iron chelator isolated from a bacterial cell
      membrane.
AB  - The membrane associated iron chelator of Pseudomonas aeruginosa has been
      extracted from membranes of iron-rich cells with ethanol and purified by reverse
      phase HPLC. Using 13C NMR and FAB mass spectroscopy, the structure of the
      chelator has been determined to be 4-hydroxy-2-nonylquinoline. This compound has
      been previously isolated and named pseudan IX, a name which we use here. We
      synthesized pseudan IX and show that the spectral properties of the synthesized
      compound and the purified compound are nearly identical. Also purified from the
      ethanol extract of membranes is 4-hydroxy-2-heptylquinoline, i.e., pseudan VII.
      Bacterially purified pseudan IX binds iron as indicated by the incorporation of
      radiolabeled iron into the chelator and by the formation of pink micelles in a
      concentrated ethanol extract. The formation of pink micelles upon addition of
      iron to the synthesized compound indicates that it binds iron.

PMID- 11846437
TI  - Psychoneuroimmunology of depression: clinical implications.
AB  - Psychoneuroimmunology is a field that investigates the interactions between the
      brain and the immune system. One important goal of this field of research is to
      translate basic research in order to understand how behavior affects health and
      resistance to disease in humans. This review evaluates the impact of depression
      on morbidity and mortality risk and asks whether neuroimmune mechanisms
      contribute to this association. Examples are drawn from three diseases:
      cardiovascular disease, infectious disease, and rheumatoid arthritis. Finally,
      the potential for biobehavioral interventions to impact psychological adaptation
      and the course of immune related disease is discussed.

PMID- 11846438
TI  - Comparison of calcitonin gene-related peptide release from rat lymphocytes and
      dorsal root ganglia neurons.
AB  - Calcitonin gene-related peptide (CGRP), a neuropeptide contained in primary
      sensory neurons, has been demonstrated to be synthesized and released by rat
      lymphocytes in our previous studies. In this study, the release properties and
      molecular characteristics of CGRP such as immunoreactivity (CGRP-LI) from
      lymphocytes were compared with those from dorsal root ganglia (DRG) neurons by
      using CGRP-specific RIA, reverse-phase HPLC, and RT-PCR. Con A and IL-2 could
      trigger CGRP-LI release from lymphocytes in a time-dependent manner. After 3 days
      stimulation with 4 microg/ml Con A, the level of CGRP-LI released by lymphocytes
      was increased from 77.4 +/- 9.6 pg/10(8) cells to 191.1 +/- 13.6 pg/10(8) cells
      and increased further to 374.5 +/- 38.3 pg/10(8) cells after 5 days. Stimulation
      with 750 U/ml human IL-2 recombinant (rhIL-2) caused a significantly elevated
      CGRP-LI release from 75.4 +/- 6.5 pg/10(8) cells to 266.2 +/- 16.2 pg/10(8) cells
      after 3 days and to 469.1 +/- 43.2 pg/10(8) cells after 5 days. Con A and IL-2
      also augmented CGRP mRNA expression in lymphocytes. In the tested period (1-5
      days), Con A and rhIL-2 had no stimulating effect on CGRP release from DRG
      neurons. In contrast, a high concentration of potassium and LPS could induce an
      acute release of CGRP from DRG neurons, but not from lymphocytes. Lymphocyte
      released CGRP-LI was shown to coelute with synthetic rat CGRP (rCGRP) and DRG
      neuron-released CGRP by reverse-phase HPLC. In addition, to displace (125)I-CGRP
      from CGRP antibody by lymphocyte-released CGRP-LI was similar to that by
      synthetic rCGRP. These data suggest that lymphocyte- and nerve-derived CGRP-LI
      are similar in terms of immunological characteristics, molecular size, and
      polarity. However, lymphocytes secrete CGRP-LI in response to different stimuli
      compared to nerve-derived CGRP.

PMID- 11846440
TI  - Elevated plus maze behavior, auditory startle response, and shock sensitivity in
      predisease and in early stage autoimmune disease MRL/lpr mice.
AB  - Behaviors indicative of anxiety have been suggested to emerge with the onset of
      autoimmune disease in MRL/MpJ-Fas(lpr) (MRL/lpr) mice. This study extends the
      behavioral characterization of MRL/lpr and congenic MRL/MpJ+/+ (MRL/+) mice using
      the elevated plus maze (EPM), acoustic startle response, and foot-shock
      sensitivity tasks. In the elevated plus maze, predisease MRL/lpr mice exhibited
      less anxiety while MRL/lpr mice in the early stage of autoimmunity did not differ
      from age-matched control MRL/+ mice. MRL/lpr mice exhibited lower startle
      responses compared to MRL/+ mice. Similarly, predisease MRL/lpr mice were less
      reactive to various foot-shock levels than MRL/+ mice. Both the MRL/lpr and the
      MRL/+ strains exhibited startle habituation deficits, implicating the background
      MRL strain in the impairment in this process. These data do not support the
      hypothesis that increased anxiety is apparent with the emergence of autoimmune
      disease in MRL/lpr mice; however, anxiety may appear as the disease advances.

PMID- 11846439
TI  - The effects of chemical sympathectomy on T-cell cytokine responses are not
      mediated by altered peritoneal exudate cell function or an inflammatory response.
AB  - Ablation of the sympathetic nervous system by chemical sympathectomy is a
      standard model for the study of sympathetic nervous system regulation of immune
      function. We have previously documented that chemical denervation results in
      enhanced antigen-specific, but suppressed mitogen-induced, cytokine production by
      spleen cells. In our investigation into the mechanisms of sympathectomy-induced
      immune alterations, we first evaluated the peritoneal environment into which the
      protein antigen keyhole limpet hemocyanin is administered. Denervation resulted
      in increased production of tumor necrosis factor-alpha by peritoneal exudate
      cells and these cells appeared to have enhanced antigen presenting capability. We
      hypothesized that nerve terminal destruction may be inducing an inflammatory
      response by monocyte/macrophages and other cell types throughout the periphery
      that could differentially alter subsequent mitogen versus antigen-specific
      responses. However, no evidence of sympathectomy-induced systemic or local
      splenic inflammatory responses was observed, as indicated by measuring the
      proinflammatory cytokines tumor necrosis factor-alpha and interleukin-1beta.
      These experiments indicate that an inflammatory response is not likely to be
      responsible for sympathectomy-induced immune alterations, eliminating a potential
      confounding factor in interpreting sympathectomy studies.

PMID- 11846441
TI  - Chemical sympathectomy alters numbers of splenic and peritoneal leukocytes.
AB  - Sympathectomy of BALB/c mice that were injected with either Listeria
      monocytogenes or saline did not affect the total number of splenic leukocytes
      measured 1-3 days after injection, but sympathectomy did increase the percentages
      of neutrophils in the spleens of both infected and uninfected mice. By contrast,
      sympathectomy was associated with increased numbers of peritoneal exudate cells
      (PEC) and peritoneal macrophages in both groups of mice. Sympathectomy did not
      affect tumor necrosis factor-alpha, interleukin-12, or interferon-gamma
      production in cultured splenocytes or PEC in either infected or uninfected mice.

PMID- 11846442
TI  - Stress-induced susceptibility to bacterial infection during cutaneous wound
      healing.
AB  - Psychological stress delays wound healing and decreases immune/inflammatory
      responses required for bacterial clearance. To determine if stress increases the
      susceptibility to wound infection, female SKH-1 mice were subjected to restraint
      stress (RST) beginning 3 days prior to the placement of cutaneous wounds. Viable
      bacteria were quantified from harvested wounds. RST delayed healing by 30% and
      caused a 2- to 5-log increase in opportunistic bacteria (e.g., Staphylococcus
      aureus) when compared to wounds from control animals (p <.05). By day 7, 85.4% of
      the wounds from RST mice had bacterial counts predictive of infection compared to
      27.4% from control mice (p <.001). To assess the role of RST-induced
      glucocorticoids in bacterial clearance, mice were treated with the glucocorticoid
      receptor antagonist RU486. RU486 reduced opportunistic bacteria by nearly 1 log
      in wounds from RST mice (p <.05). Thus, stress impairs bacterial clearance during
      wound healing, resulting in a significant increase in the incidence of
      opportunistic infection.

PMID- 11846443
TI  - Pertubation of beta1 integrin function using anti-sense or function-blocking
      antibodies on corneal cells grown on fibronectin and tenascin.
AB  - During corneal development, neural crest derivatives from the periocular
      mesenchyme migrate into the cornea and differentiate into corneal fibroblasts.
      During this time, these cells interact with a variety of extracellular matrices
      for proper orientation and development. In the present studies, we have examined
      the interaction of beta(1) integrins on periocular mesenchyme cells (POM) and
      corneal fibroblasts (CF) with fibronectin and tenascin by perturbing the function
      of this integrin. POM and CF attached and spread to a much greater extent on
      fibronectin than on tenascin. An antibody against beta(1) integrin, CSAT,
      decreased spreading and attachment, and resulted in a lack of immuno-detectable
      beta(1) integrin in focal adhesions on fibronectin; few beta(1) positive focal
      adhesions were observed in cells grown on tenascin. An anti-sense retroviral
      construct decreased endogenous levels of beta(1) integrin protein, and caused
      decreased attachment and spreading as well as sparse, disorganized focal
      adhesions. These data indicate that in vitro, both POM and CF have beta(1)
      integrins that interact with fibronectin and allow them to attach and spread,
      while tenascin is anti-adhesive. Further studies using both of these experimental
      paradigms will clarify whether these interactions also occur in vivo.

PMID- 11846444
TI  - Caffeine and other xanthines as cytochemical blockers and removers of
      heterocyclic DNA intercalators from chromatin.
AB  - Caffeine (CAF) and other xanthines non-covalently bind with the cationic
      fluorescent dye acridine orange (AO) and with other heterocyclic mutagens and
      carcinogens that are known to intercalate into double-stranded DNA (dsDNA).
      Fluorescence microscopy and spectrofluorometry studies were employed to test the
      ability of caffeine and certain other methyl substituted xanthines, with
      different binding affinities for AO, to inhibit and to reverse the intercalation
      of AO and other heterocyclic agents from intercalation with the DNA of nuclear
      chromatin of air-dried cells. Results indicated that xanthines with binding
      affinity for AO greater than 150 m(-1) block the AO molecule in a concentration
      dependent manner and comply with mass action kinetics. Thus CAF and other
      xanthines can be used to either inhibit intercalation of AO into nuclear DNA or
      to remove AO once intercalated into nuclear DNA. The interactions between other
      planar heterocyclics, xanthines, and nuclear chromatin dsDNA were also found to
      be non-covalent. Studies are needed to determine the ability of CAF and other
      xanthines to block and/or remove polyaromatic hydrocarbon (PAH) intercalators
      from the DNA of living cells.

PMID- 11846445
TI  - Glyceraldehyde-3-phosphate dehydrogenase associates with actin filaments in serum
      deprived NIH 3T3 cells only.
AB  - The in vitro interaction between the glycolytic enzyme glyceraldehyde-3-phosphate
      dehydrogenase (GAPDH) and cytoskeletal elements is well documented. To verify
      this association within cells, the intracellular distribution of GAPDH under
      various metabolic conditions has been investigated in immunostained cells or
      cells expressing GAPDH as a GFP fusion protein. GAPDH was homogeneously
      distributed in the cytoplasm and no interaction of GAPDH with cytoskeletal
      elements, neither with microfilaments nor microtubules or intermediate filaments,
      was detectable. In living cells expressing GFP-GAPDH, stress fibres were excluded
      from the fluorescence. In contrast to proliferating cells, the cytoplasmic GAPDH
      of serum-depleted cells was not homogeneously distributed, but colocalised with
      stress fibres. The mechanism for stimulating this actin-binding affinity was
      independent of the NO-signalling pathway. The results support the idea of a
      specialised function for the interaction of GAPDH and cytoskeletal elements,
      rather than a general function, as e.g. microcompartmentalization of glycolytic
      enzymes.

PMID- 11846446
TI  - Overexpression of the type II transforming growth factor-beta receptor inhibits
      fibroblasts proliferation and activates extracellular signal regulated kinase and
      c-Jun N-terminal kinase.
AB  - Transforming growth factor-beta (TGF-beta) is a bimodal regulator of cellular
      growth. The cellular effects of TGF-beta depend on the intensity of signals
      emanating from TGF-beta receptors. Low levels of receptor activity are sufficient
      to stimulate cell proliferation, while higher degrees of receptor activation are
      associated with growth inhibition. To study the mechanisms of these effects, a
      tetracycline-inducible expression system was used to overexpress type II TGF-beta
      receptors in NIH 3T3 fibroblasts. Overexpressed type II TGF-beta receptors
      suppressed fibroblast proliferation elicited by TGF-beta1, fibroblast growth
      factor (FGF) or platelet-derived growth factor (PDGF). Accompanying these anti
      proliferative effects, increases in extracellular-signal regulated kinase (ERK)
      and c-Jun N-terminal kinase (JNK) activity were detected. Furthermore, PDGF alpha
      , but not PDGF beta-receptor protein levels were reduced by type II TGF-beta
      receptor overexpression. In conclusion, our system is an excellent tool to study
      the molecular mechanisms of growth inhibition by TGF-beta in fibroblasts.
      Activation of JNK and ERK, or modulation of PDGF receptor expression may be
      involved in this process.

PMID- 11846447
TI  - Production and characterization of Escherichia coli enterohemolysin and its
      effects on the structure of erythrocyte membranes.
AB  - Hemolysins are cell-damaging protein toxins produced by pathogenic bacteria,
      which are usually released into the extracellular medium. Escherichia coli
      enterohemolysin is an intracellular toxin produced during the log phase of
      growth, with a maximal intracellular accumulation in the late log phase. In the
      present study, we have employed electron microscopy and SDS-PAGE to assess the
      effects of enterohemolysin on erythocyte membranes from different species. The
      erythrocyte cell damage began immediately after exposure to enterohemolysin with
      chemically detectable changes in cell membrane permeability, and the formation of
      surface lesions which increased rapidly in size. This process resulted in
      complete cell destruction. Ring-shaped structures with a diameter of 10nm were
      observed by electron microscopy after treatment of horse erythrocyte membranes
      with enterohemolysin. The ring structures were found clustered and irregularly
      distributed on the surface of the membranes. Following incubation of the toxin
      with horse erythrocyte ghosts and detergent-solubilization, the enterohemolysin
      was isolated from the cytoplasm in its membrane-bound form by sucrose density
      gradient. SDS-PAGE and silver staining of deoxycholate-solubilized target
      membranes revealed heterogeneous forms of the toxin. By using SDS-PAGE and gel
      filtration, the molecular weight of the toxin was estimated to be 35 kDa. With
      respect to species specificity, horse erythrocytes showed the highest sensitivity
      to the enterohemolysin, followed by human and guinea pig erythrocytes. The
      hemolytic sensitivity correlated with the toxin binding capacity of erythrocyte
      membranes of different animal species. The degree of hemolysis was unaffected by
      temperature in the range of 4 degrees C-37 degrees C and was optimal at pH 9.0.
      In contrast to pore-forming cytolysins, the hemolytic activity of enterohemolysin
      was enhanced continuously in the presence of increasing concentrations of dextran
      4 and dextran 8 within the range of 5 to 30 mM. Trypsin sensitivity of membrane
      bound enterohemolysin indicates that the cell surface is the most likely target
      site for this toxin. Additionally, the fact that proteinase and phosphatase
      inhibitors failed to inhibit lysis suggests that enterohemolysin alters and
      disrupts cell membranes by a detergent-like mechanism.

PMID- 11846448
TI  - Modulation of c-myc and c-fos gene expression in regenerating rat liver by 2
      mercaptopropionylglycine.
AB  - Expression of the two proto-oncogenes, c- myc and c- fos, in proliferating liver,
      and the modulation of their expression by 2-mercaptopropionylglycine (MPG) has
      been investigated. A significant increase in the expression of both c-myc and c
      fos was observed, attaining a peak at 30 min, followed by a gradual decline for
      8h after partial hepatectomy. Treatment of partially hepatectomized animals with
      MPG resulted in a significant decrease in the expression of both genes, the
      decrease being more marked in c- myc mRNA levels. At later time points, there was
      a very small rise in the mRNA levels of these genes in MPG-treated animals but
      they still remained much lower than the peak levels observed in both genes 30 min
      after surgery. A decline in the recovery of liver weight in MPG-treated animals
      was also observed.

PMID- 11846449
TI  - Definitive expression of c-mos in late meiotic prophase leads to phosphorylation
      of a 34 kda protein in cultured rat spermatocytes.
AB  - To investigate the role of c-mos in rat spermatogenesis, expression of c-mos, MAP
      kinase kinase (MAPKK), MAP kinase (MAPK), cdc2 and protein kinase A (PKA) by
      spermatogenic cell culture of 14 day-old rats was examined. MAPKK and PKA
      expressions were constitutive, whereas the expression of MAPK and cdc2 in
      spermatogonia initially decreased, but later increased on meiotic maturation of
      spermatocytes. c-mos expression was definitive of late meiotic prophase. c-mos
      immunoprecipitates prepared from the c-mos-enriched fraction (pI9.0-9.6) could
      form complex(es) in the cultured spermatogenic cell lysates. In vitro
      phosphorylation of the c-mos immune complexes revealed a 34 kDa protein that was
      phosphorylated at serine and threonine residues as a target of the c-mos signal.
      Its pI value was 4.4-4.5, and cdc2 was not detected, making it different from
      cdc2 (p34). These results suggest that the phosphorylation of the 34 kDa protein
      by the c-mos signal may play a crucial role in the meiotic division of rat
      spermatocytes.

PMID- 11846450
TI  - Inability of 50 Hz magnetic fields to regulate PKC- and Ca(2+)-dependent gene
      expression in Jurkat cells.
AB  - We have previously reported that the T cell line Jurkat registers the exposure of
      a sinusoidal extremely low frequency magnetic field at the level of the plasma
      membrane, resulting in activation of the tyrosine kinase p56(lck), increase in
      inositol-3-phosphate levels and increase in intracellular calcium concentration
      within minutes. To elucidate if these events associated with changes in
      intracellular calcium ion levels were biologically significant, transient
      transfections of Jurkat cells were performed with calcium-ion dependent reporter
      constructs. Three different enhancer/promoter constructs were studied coupled to
      the luciferase reporter gene. The luciferase activity of each construct was
      measured after treatment of transfected cells to EMF exposure alone, or in
      combination with ionomycin, phorbol ester or cross-linking anti-CD3 antibodies.
      There was no indication that the used EMFs could influence any of these reporter
      constructs.

PMID- 11846451
TI  - Early progression from dimethyl sulfoxide-induced G(0)/G(1) arrest in L(1210)
      cells.
AB  - Recently, dimethyl sulfoxide (DMSO) has been used as a convenient cryoprotectant
      for stem cells in stem cell transplantation using allogenic peripheral blood or
      umbilical cord blood. As the stem cells have a multipotency, clarification of the
      extent of cell proliferation after transplantation is difficult. In the present
      study, DMSO gradually induced G(0)/G(1) arrest in mouse leukemia L(1210) cells
      with good cell viability. After removal of DMSO, the cells proliferated
      appropriately, resulting in expression of the DNA-synthesizing enzymes
      thymidylate synthase and thymidine kinase within 6h, and the cells entering into
      S phase within 12h. The sequence was followed by the marked activation of both
      enzymes within 24h and the increase of bromodeoxyuridine (BrdU) immunoreactive (S
      phase) cells with rapid cell proliferation within 36 h. In conclusion, mouse
      leukemia L(1210) cells, which were treated with 1.5% DMSO for 96 h, tolerated the
      treatment and reversed the cell cycle arrest within 36 h.

PMID- 11846453
TI  - A model B-cell superantigen and the immunobiology of B lymphocytes.
AB  - Recent reports have shown that protein A of Staphylococcus aureus (SpA) is a
      specific toxin for B cells by virtue of specific binding interactions with
      conserved sites on the V(H) region of the B-cell antigen receptor. The structural
      basis for these Fab-binding interactions has recently been revealed in
      crystallographic analyses, which have demonstrated many similarities with the
      interactions of T-cell superantigens. Investigations of the in vivo response to
      SpA have illustrated how a B-cell superantigen can be used to provide a window
      for examining fundamental principles that underlie the immunobiology of B
      lymphocytes.

PMID- 11846452
TI  - Endogenous retroviruses in systemic lupus erythematosus: candidate lupus viruses.
AB  - Although the etiology of systemic lupus erythematosus (SLE) remains unclear,
      there is substantial circumstantial evidence that the development of SLE is
      dependent on environmental, genetic, and retroviral factors. SLE patients produce
      high titer antibodies to various retroviral proteins, including Gag, Env, and Nef
      of HIV and HTLV, in the absence of overt retroviral infection. We review the
      factors linking HERVs to SLE and consider the various processes utilized by
      endogenous retroviruses in the etiopathogenesis of SLE. In particular, we
      consider the role of HTLV-1-related endogenous sequence (HRES-1) in SLE. We
      propose that molecular mimicry between HRES-1 and the small ribonucleoprotein
      complex initiates the production of autoantibodies, leading to immune complex
      formation, complement fixation, and pathological tissue deposition.

PMID- 11846454
TI  - Prevention of murine experimental autoimmune orchitis by recombinant human
      interleukin-6.
AB  - We studied the effect of exogenously administered recombinant human interleukin
      (IL)-6 on the development of experimental autoimmune orchitis (EAO) in C3H/Hej
      mice. IL-6 significantly reduced histological signs of EAO and appearance of
      delayed type hypersensitivity against the immunizing testicular germinal cells.
      The effect was seen even though the cytokine was administered for only 6
      consecutive days and 2 weeks after immunization.

PMID- 11846455
TI  - The use of bioinformatics to identify the genomic structure of the gene that
      encodes neutrophil antigen NB1, CD177.
AB  - The gene encoding neutrophil alloantigen NB1, CD177, is highly homologous to a
      gene overexpressed in polycythemia vera neutrophils, polycythemia rubra vera-1
      (PRV-1). The cDNAs of both genes have been cloned, but their genomic structure is
      unknown. The purpose of this study was to determine the intron-exon organization
      of NB1 and PRV-1 and discern if they are separate members of a homologous gene
      family or alleles of the same gene. GenBank's human genome sequences were probed
      in silico with PRV-1's 1605-nucleotide coding sequence. Searches identified two
      adjacent bacterial artificial chromosomes (BACs) on chromosome 19q13.2: BC338531
      and BC52850. BC338531 contained sequences 100% homologous to the first 654
      nucleotides of PRV-1. Comparison of coding and genomic sequences allowed us to
      separate this region into exons 1 through 5, interrupted by five introns. BC52850
      contained sequences 95% homologous to nucleotides 413 through 1605 of PRV-1,
      organized into exons 4 through 9. However, the orientation of PRV-1-homologous in
      the first BAC was plus-plus and of the second was plus-minus, indicating they
      could not be portions of the same gene. The GenBank sequence of BC338531 was
      incomplete, creating a sequence gap in chromosome 19q13.2. Evaluation of
      BC338531's unfinished sequences in Joint Genome Institute public databases
      allowed us to complete the gap and revealed that BC338531 contained sequences 98%
      homologous to all nine PRV-1 exons followed by a second gene consisting of exons
      9 through 4. Most likely, NB1 and PRV-1 are alleles of the same gene, CD177, and
      the duplication of exons 4 through 9 is a pseudo gene.

PMID- 11846456
TI  - Recurrent aerosol antigen exposure induces distinct patterns of experimental
      allergic asthma in mice.
AB  - Patients with allergic asthma present clinically with chronic or intermittent
      disease caused by either persistent or periodic allergen exposure. We sought to
      generate clinically relevant disease in mice, which would reflect the relapsing,
      remitting, and constant nature of this syndrome. We generated and compared acute
      onset, remission, relapse, and overt phases of the disease and found that acute
      disease was characterized by airway hyperreactivity, eosinophilic lung
      inflammation, excessive mucus production, and antigen-specific antibody and was
      rapidly followed by a remission. Mice rechallenged with aerosol antigen during
      the remission or treated with repeated aerosol challenges developed relapse and
      overt disease, respectively. Recurrent antigen exposure induced a progressive
      increase in bronchoalveolar lavage fluid immunoglobulin, mucus production, and a
      change in inflammatory infiltrates indicating a transition from acute to chronic
      inflammation. These data demonstrate distinct phases of disease representing a
      clinical spectrum of experimental allergic asthma and may have important
      implications for new treatment strategies.

PMID- 11846458
TI  - Antineutrophil cytoplasmic antibodies, anti-Saccharomyces cerevisiae antibodies,
      and specific IgE to food allergens in children with inflammatory bowel diseases.
AB  - Differential diagnosis between ulcerative colitis (UC) and Crohn's disease (CD)
      is difficult in the initial phases in pediatric patients with inflammatory bowel
      diseases (IBD). This study was performed to determine the significance of anti
      neutrophil cytoplasmic antibodies (ANCA) and anti-Saccharomyces cerevisiae
      antibodies (ASCA) in IBD. ANCA were specified with regard to their antigenic
      specifity, significance to the diagnosis, and correlation of titer with the
      disease activity. The occurrence of food allergy was questioned, too. Serum
      samples from 44 children with UC (n = 23) or CD (n = 21) and from disease-control
      children (coeliac disease, n = 21) were analyzed for IgG ANCA, ANCA target
      antigens, IgA and IgG ASCA, and IgE to food allergens. Results show that ANCA
      occur more frequently in UC than in CD and disease-control (74, 24, and 10%,
      respectively). The presence of ANCA does not reflect disease activity. Antigenic
      specificity does not differ in any group. IgA-ASCA are found more often in
      patients with CD (76% versus 17% in UC). The testing for both ANCA and ASCA
      enabled clear-cut differential diagnosis between UC and CD based on the high
      specificity (ANCA+ ASCA- 92.5% for UC, ANCA- ASCA+ 93.2% for CD). Specific IgE to
      food allergens were found in 8.7, 14.3, and 23.8% of patients with UC, CD, and
      coeliac disease, respectively. We conclude that combined testing of ANCA and ASCA
      represents a valuable tool in the differential diagnosis between UC and CD in
      pediatric patients, minimizing invasive diagnostic procedures. Monitoring of
      ANCA, its specificity, and titer determination does not bring more information.
      Testing for specific IgE to food allergens may be considered in individual
      patients.

PMID- 11846457
TI  - CD4+ T-lymphocyte nadir and the effect of highly active antiretroviral therapy on
      phenotypic and functional immune restoration in HIV-1 infection.
AB  - To evaluate the effects of the timing of highly active antiretroviral therapy
      (HAART) on immune reconstitution, we compared lymphocyte subpopulations and
      lymphocyte proliferation (LP) in response to Candida albicans, cytomegalovirus,
      HIV p24, Mycobacterium avium complex, pokeweed mitogen, streptokinase, and
      tetanus toxoid in 43 patients with pretherapy advanced, moderately advanced, and
      early chronic HIV-1 infection. All patients had recent CD4+ T-cell counts
      >450/microl and HIV RNA <400 copies/ml for >12 months. CD4+ nadirs were
      positively correlated with recent numbers of CD4+ T-cells (P < 0.001), memory
      cells (P < 0.001), and naive CD4+ T-cells (P < 0.05) and CD4+ CD28+ T-lymphocytes
      (P < 0.05) and were negatively correlated with recent CD8+ T-lymphocyte counts (P
      < 0.05). Only CD4+ naive T-cells normalized when HAART was initiated at lower
      CD4+ T-cell levels. Fifty-three percent of patients had LP responses to HIV p24
      antigen. While LP responses to prevalent antigens were usually present, responses
      to tetanus toxoid were more common with higher CD4+ T-lymphocyte nadirs (P <
      0.05). Delaying HAART may limit phenotypic and functional immune restoration in
      HIV-1 infection.

PMID- 11846459
TI  - Prognostic significance of circulating IL-10 and IL-6 serum levels in colon
      cancer patients undergoing surgery.
AB  - The prognostic significance of IL-10 and IL-6 serum levels in colon cancer
      patients undergoing surgery was investigated. To this end, 50 candidate patients
      with colon cancer for surgery were admitted to the study. Of these, 30 could be
      subjected to a potentially curative surgery. Cytokine serum levels at several
      time points before and after surgery were measured by ELISA. Circulating levels
      of IL-10 and IL-6 were found to be elevated in cancer patients with respect to
      controls. Both IL-10 and IL-6 serum levels were demonstrated to predict the
      likelihood of curative surgery (predictive accuracy, 83.3%). IL-10 serum levels
      returned to normal in all but 6 patients who underwent curative surgery. These
      latter had tumor recurrence (predictive accuracy, 100%). In contrast, IL-6 serum
      levels significantly decreased in all patients, regardless of whether cure was
      surgically achieved, but did not normalize. On multivariate analysis, basal IL-10
      serum levels were found to be among the variables significantly predicting the
      disease-free survival rate. Stepwise regression selected tumor stage, basal IL-10
      serum level, and basal CEA serum level as the best combination of variables for
      prediction of the likelihood of tumor recurrence. In conclusion, preoperative
      serum levels of IL-10 were shown to be useful markers for predicting both
      likelihood to perform curative surgery and, in combination with the 16th
      postoperative day IL-10 serum levels, tumor recurrence (predictive accuracy, 73.6
      and 96%, respectively). IL-6 serum levels were found to have a more limited
      prognostic role.

PMID- 11846460
TI  - Taurine chloramine inhibits lymphocyte proliferation and decreases cytokine
      production in activated human leukocytes.
AB  - Previously, we described the inhibition of proinflammatory mediators such as
      nitric oxide, tumor necrosis factor-alpha (TNF-alpha), and prostaglandin E2 by
      taurine chloramine (Tau-Cl) in activated rodent macrophages. We also demonstrated
      that Tau-Cl suppressed superoxide anion, IL-6, and IL-8 production in activated
      human polymorphonuclear leukocytes separated from peripheral blood. In these
      studies, we report the effect of Tau-Cl on lymphocyte proliferation and the
      production of cytokines by activated human peripheral blood mononuclear
      leukocytes. Adherent and nonadherent leukocytes were activated using
      lipopolysaccharide (LPS) and phytohemagglutinin (PHA), respectively, in the
      presence or absence of Tau-Cl. Tau-Cl significantly suppressed lymphocyte
      proliferation as measured by tritiated (3H) thymidine. Production of IL-6, IL-8,
      and IL-2 in PHA-activated nonadherent leukocytes was inhibited by Tau-Cl. The
      production of IL-1beta, IL-6, and IL-8 was also decreased in LPS-activated
      adherent monocytes by Tau-Cl. These data demonstrate that the ability of Tau-Cl
      to modulate the immune response is not species specific and extends to human
      leukocytes.

PMID- 11846461
TI  - The role of IL-4 in regulation of murine collagen-induced arthritis.
AB  - Collagen-induced arthritis (CIA) is a murine model of autoimmune-mediated
      polyarthritis. CIA can be prevented by the administration (intravenously) of CII,
      inducing regulatory CD4+ T cells which produce Th2 cytokines. However, the
      relative importance of IL-4 in suppressing arthritis remains unclear. To address
      this question, a neutralizing monoclonal antibody to IL-4 was given to mice
      treated with tolerized, CII-specific cells. The antibody significantly reversed
      the expected suppression of arthritis. Moreover, CII administered intravenously
      to DBA/1 IL4-/- mice (developed by backcrossing C57B1/6 IL4-/- to wild-type DBA/1
      mice) was completely ineffective in suppressing disease. These data support the
      importance of IL-4 in the regulation of autoimmune arthritis. Compensatory
      increases in mRNA message for other Th2 cytokines were observed, but they did not
      restore suppression of arthritis. Antibodies to CII, mostly IgG2a, were increased
      in IL4-/- mice. These studies represent a unique opportunity to analyze the role
      of IL-4 and its absence on an autoimmune murine model of arthritis.

PMID- 11846462
TI  - Monitoring of basophil activation using CD63 and CCR3 in allergy to muscle
      relaxant drugs.
AB  - Allergic or pseudoallergic reactions that occur during anesthesia have been
      increasing for the last few years. To date, the diagnosis of allergy to muscle
      relaxants remains difficult. In this respect, we developed a flow cytometric
      method for the study of drug-induced basophil degranulation using CD63 and CCR3.
      Fifty patients who developed clinical features evocative of allergic reactions
      immediately after induction of anesthesia were included and classified into two
      groups. Group 1 (n = 39) comprised true allergic patients, who developed typical
      signs of shock associated to positive skin testing. Group 2 (n = 11) consisted of
      patients whose clinical history was not typical and skin testing was negative or
      nonconclusive. Seventeen control subjects were also studied in this report. We
      compared data from flow cytometry to skin tests, specific IgE, and histamine
      release results. Flow cytometry showed a sensitivity of 54%, while that of
      specific IgE was similar, at 62%. Interestingly, when considering the sensitivity
      of IgE + CD63 for diagnosis, we reached a sensitivity value of 80%. Of 15
      negative results for specific IgE, we found 7 positive CD63 tests, while
      histamine release gave positive results in only 2 cases. Furthermore, the CD63
      protocol showed good specificity (100%). We conclude that our flow cytometry
      protocol is a promising tool in allergy diagnosis since it is specific and
      complementary to specific IgE detection.

PMID- 11846463
TI  - IFN-gamma pretreatment augments immune complex-induced matrix metalloproteinase-1
      expression in U937 histiocytes.
AB  - We reported recently that immune complexes (ICs) induced matrix metalloproteinase
      1 (MMP-1) expression in U937 histiocytes. The present study was undertaken to
      determine the effect of pretreatment of U937 cells with interferon-gamma (IFN
      gamma) on IC-induced MMP-1 expression. Our flow cytometry studies showed that IFN
      gamma upregulated the surface expression of FcgammaRI, but not FcgammaRII.
      Results also showed that pretreatment of the cells with IFN-gamma augmented LDL
      containing IC (LDL-IC)-induced MMP-1 secretion in a dose- and time-dependent
      manner. Furthermore, Northern blot analysis revealed that IFN-gamma pretreatment
      led to a marked increase in MMP-1 mRNA. Finally, we demonstrated that PD98059 was
      able to block LDL-IC-induced MMP-1 secretion, regardless of whether the cells
      were pretreated with IFN-gamma or not, suggesting that IFN-gamma pretreatment did
      not alter the essential role of the ERK signaling pathway in LDL-IC-induced MMP-1
      expression. In conclusion, the present study has demonstrated that IFN-gamma
      pretreatment augments LDL-IC-induced MMP-1 expression in U937 cells, thus
      elucidating an immune mechanism potentially involved in plaque destabilization.

PMID- 11846464
TI  - The trehalose myth revisited: introduction to a symposium on stabilization of
      cells in the dry state.
AB  - This essay is an introduction to a series of papers arising from a symposium on
      stabilization of cells in the dry state. Nearly all of these investigations have
      utilized the sugar trehalose as a stabilizing molecule. Over the past two decades
      a myth has grown up about special properties of trehalose for stabilization of
      biomaterials. We review many of such uses here and show that under ideal
      conditions for drying and storage trehalose has few, if any, special properties.
      However, under suboptimal conditions trehalose has some distinct advantages and
      thus may remain the preferred excipient. We review the available mechanisms for
      introducing trehalose into the cytoplasm of living cells as an introduction to
      the papers that follow.

PMID- 11846465
TI  - Overexpression of trehalose synthase and accumulation of intracellular trehalose
      in 293H and 293FTetR:Hyg cells.
AB  - A humanized clone containing the trehalose-6-phosphate synthase and trehalose-6
      phosphate phosphatase (otsA/B) has been constructed. Using the Gateway Cloning
      System (Invitrogen, Inc.), the otsA/B genes have been placed under the control of
      the CMV promoter (pEXPcmv-otsA/B) or the CMV promoter and the tet operator (pEXP
      cmv TetO-otsA/B). The pEXPcmv-otsA/B clone has been introduced into 293H cells
      using LIPOFECTAMINE 2000 and the intracellular concentration of trehalose has
      been evaluated. The 293H cells accumulate 4-5 microg trehalose/mg dry weight and
      this concentration increases to 7-10 microg trehalose/mg dry weight if trehalose
      is included in the growth medium. The pEXPcmv TetO-otsA/B clone has been
      transfected into 293FTetR:Hyg cells which contain the tet repressor integrated
      into the genome. When these transfected cells are grown in the absence of
      tetracycline, no intracellular trehalose is detected. Inclusion of 0.3 microg/ml
      tetracycline in the growth medium results in the accumulation of 11-14 microg
      trehalose/mg dry weight, a value which increases to 19-20 microg trehalose/mg dry
      weight if trehalose is included in the growth medium. The data for the
      293FTetR:Hyg cells indicate that intracellular trehalose accumulates in response
      to the addition of tetracycline. This system will allow us to manipulate the
      intracellular concentration of trehalose and to evaluate the desiccation
      tolerance of these cells as a function of intracellular trehalose concentration.

PMID- 11846467
TI  - Anhydrobiotic engineering of bacterial and mammalian cells: is intracellular
      trehalose sufficient?
AB  - Anhydrobiotic engineering aims to confer a high degree of desiccation tolerance
      on otherwise sensitive living organisms and cells by adopting the strategies of
      anhydrobiosis. Nonreducing disaccharides such as trehalose and sucrose are
      thought to play a pivotal role in resistance to desiccation stress in many
      microorganisms, invertebrates, and plants, and in vitro trehalose is known to
      confer stability on dried biomolecules and biomembranes. We have therefore tested
      the hypothesis that intracellular trehalose (or a similar molecule) may be not
      only necessary for anhydrobiosis but also sufficient. High concentrations of
      trehalose were produced in bacteria by osmotic preconditioning, and in mammalian
      cells by genetic engineering, but in neither system was desiccation tolerance
      similar to that seen in anhydrobiotic organisms, suggesting that trehalose alone
      is not sufficient for anhydrobiosis. In Escherichia coli such desiccation
      tolerance was achievable, but only when bacteria were dried in the presence of
      both extracellular trehalose and intracellular trehalose. In mouse L cells,
      improved osmotolerance was observed with up to 100 mM intracellular trehalose,
      but desiccation was invariably lethal even with extracellular trehalose present.
      We conclude that anhydrobiotic engineering of at least some microorganisms is
      achievable with present technology, but that further advances are needed for
      similar desiccation tolerance of mammalian cells.

PMID- 11846466
TI  - Membrane reorganization during chilling: implications for long-term stabilization
      of platelets.
AB  - This essay is a review of the various biophysical and biochemical events that
      make up the factors responsible for platelet cold-induced activation. It
      describes the formation of large membrane domains composed of raft aggregates
      that occur during chilling and storage. It also presents strong evidence that
      platelet membranes undergo lateral phase separation during prolonged storage in
      the cold and suggests that raft aggregation and lateral phase separation are key
      events which must be obviated to stabilize platelets and store them either in the
      frozen or in the dry state.

PMID- 11846469
TI  - Induction of desiccation tolerance in plant somatic embryos: how exclusive is the
      protective role of sugars?
AB  - Plant somatic embryos usually lack desiccation tolerance. They may acquire such a
      tolerance upon preculture in the presence of abscisic acid (ABA), followed by
      slow drying, but not fast drying. ABA causes torpedo-shaped somatic embryos to
      lose their chlorophyll, suspend growth, exhibit low rates of respiration, and
      maintain elevated sucrose contents. The subsequent slow drying leads to a partial
      conversion of sucrose into oligosaccharides and the expression of dehydrin
      transcripts. Slow-dried, desiccation-tolerant somatic embryos have stable
      membranes, retain their native protein secondary structure, and have a densely
      packed cytoplasmic glassy matrix. Fast-dried, desiccation-sensitive somatic
      embryos experience some loss of phospholipids and an increase in free fatty
      acids. Their proteins show signs of denaturation and aggregation, and the glassy
      matrix has reduced hydrogen bonding. The reduced conversion of sucrose into
      oligosaccharides appears not to underlie dehydration injury. Proteins in slow
      dried somatic embryos, not pretreated with ABA, also show signs of denaturation,
      which might be attributed to low sugar contents. We conclude that by reducing
      cellular metabolism, ABA maintains high sugar contents. These sugars contribute
      to the stability of membranes, proteins, and the cytoplasmic glassy matrix,
      whereas slow drying permits a further fine tuning of this stability. Partitioning
      of endogenous amphiphiles from the cytoplasm into membranes during drying may
      cause membrane perturbance, although it might confer protection to membranes in
      the case of amphiphilic antioxidants. The perturbance appears to be effectively
      controlled in desiccation-tolerant systems but not in sensitive systems, for
      which we suggest dehydrins are responsible. In this context, the low desiccation
      tolerance in the presence of ample sugars is discussed.

PMID- 11846468
TI  - Inactivation of two homologues of proteins presumed to be involved in the
      desiccation tolerance of plants sensitizes Deinococcus radiodurans R1 to
      desiccation.
AB  - Mutational inactivation of the genes designated DR1172 and DRB0118 in Deinococcus
      radiodurans R1 greatly sensitizes this species to desiccation, but not to
      ionizing radiation. These genes encode proteins that share features with the
      desiccation-induced LEA76 proteins of many plants and the PCC13-62 protein of
      Craterostigma plantagineum, suggesting that D. radiodurans may serve as a useful
      model for the study of desiccation tolerance in higher organisms.

PMID- 11846470
TI  - Non-disaccharide-based mechanisms of protection during drying.
AB  - Few tissues or organisms can survive the removal of nearly all their intra and
      extracellular water. These few have developed specialized adaptations to protect
      their cellular components from the damage caused by desiccation and rehydration.
      One mechanism, common to almost all such organisms, is the accumulation of
      disaccharides within cells and tissues at the onset of dehydration. This
      adaptation has been extensively studied and will not be considered in this
      review. It has become increasingly clear that true desiccation tolerance is
      likely to involve several mechanisms working in concert; thus, we will highlight
      several other important and complimentary adaptations found especially in the
      dehydration-resistant tissues of higher plants. These include the scavenging of
      reactive oxygen species, the down-regulation of metabolism, and the accumulation
      of certain amphiphilic solutes, proteins, and polysaccharides.

PMID- 11846471
TI  - Beneficial effect of intracellular trehalose on the membrane integrity of dried
      mammalian cells.
AB  - Recently, there has been much interest in using trehalose and other small
      carbohydrates to preserve mammalian cells in the dried state as an alternative to
      cryopreservation. Here, we report on the successful preservation of plasma
      membrane integrity after drying, as a first step toward full preservation of
      mammalian cells. Trehalose was introduced into cells using a genetically
      engineered version of alpha-hemolysin, a pore-forming protein; the cells were
      then dried and stored for weeks at different temperatures with approximately 90%
      recovery of the intact plasma membrane. We show that protection of the plasma
      membrane by internal trehalose is dose dependent and estimate the amount of
      internal trehalose required for adequate protection to be approximately 10(10)
      molecules/cell. In addition, a minimal amount of water (approximately 15 wt%)
      appears to be necessary. These results show that a key component of mammalian
      cells can be preserved in a dried state for weeks under mild conditions (-20
      degrees C and 5% relative humidity) and thereby suggest new approaches to
      preserving mammalian cells.

PMID- 11846472
TI  - Recovery of human mesenchymal stem cells following dehydration and rehydration.
AB  - As cell therapies advance from research laboratories to clinical application,
      there is the need to transport cells and tissues across long distances while
      maintaining cell viability and function. Currently cells are successfully stored
      and shipped under liquid nitrogen vapor. The ability to store these cells in the
      desiccated state at ambient temperature would provide tremendous economic and
      practical advantage. Human mesenchymal stem cells (hMSCs) have broad potential
      uses in tissue engineering and regeneration since they can differentiate along
      multiple lineages and support hematopoeisis. The current research applied recent
      technological advances in the dehydration and storage of human fibroblasts to
      hMSCs. Three conditions were tested: air-dried, air-dried and stored under vacuum
      (vacuum only), and incubated with 50 mM trehalose + 3% glycerol and then air
      dried and stored under vacuum (vacuum + trehalose). Plates containing dehydrated
      hMSCs were shipped from San Diego to Baltimore overnight in separate FedEx
      cardboard boxes. The hMSCs were rehydrated with 3 ml of hMSC medium and were able
      to regain their spindle-shaped morphology and adhesive capability. In addition,
      they maintained high viability and proliferation capacity. Rehydrated and
      passaged cells continued to express the characteristic hMSC surface antigen
      panel. Additionally, cells showed constitutive levels of mRNA for a stromal
      factor and, when exposed to reagents known to induce differentiation,
      demonstrated upregulation of two tissue-specific messages indicative of
      differentiation potential for fat and bone. While our preliminary findings are
      encouraging, we still need to address consistency and duration of storage by
      considering factors such as cell water content, oxygen concentration, and the
      presence of free radicals.

PMID- 11846473
TI  - It takes guts: the Drosophila hindgut as a model system for organogenesis.
AB  - The Drosophila hindgut is fruitful territory for investigation of events common
      to many types of organogenesis. The development of the Drosophila hindgut
      provides, in microcosm, a genetic model system for studying processes such as
      establishment (patterning) of an epithelial primordium, its internalization by
      gastrulation, development of left--right asymmetric looping, patterning in both
      the anteroposterior and dorsoventral axes, innervation, investment of an
      epithelium with mesoderm, reciprocal epitheliomesenchymal interactions, cell
      shape change, and cell rearrangement. We review the genetic control of these
      processes during development of the Drosophila hindgut, and compare these to
      related processes in other bilaterians, particularly vertebrates. We propose that
      caudal/Cdx, brachyenteron/Brachyury, fork head/HNF-3, and wingless/Wnt constitute
      a conserved "cassette" of genes expressed in the blastopore and later in the gut,
      involved in posterior patterning, cell rearrangement, and gut maintenance.
      Elongation of the internalized Drosophila hindgut primordium is similar to
      elongation of the archenteron and also of the entire embryonic axis (both during
      and after gastrulation), as well as of various tubules (e.g., nephric ducts,
      Malpighian tubules), as it is driven by cell rearrangement. The genes drumstick,
      bowl, and lines (which encode putative transcriptional regulators) are required
      for this cell rearrangement, as well as for spatially localized gene expression
      required to establish the three morphologically distinct subregions of the
      hindgut. Expression of signaling molecules regulated by drumstick, bowl, and
      lines, in particular of the JAK/STAT activator Unpaired at the hindgut anterior,
      may play a role in controlling hindgut cell rearrangement. Other cell signaling
      molecules expressed in the hindgut epithelium are required to establish its
      normal size (Dpp and Hh), and to establish and maintain the hindgut visceral
      mesoderm (Wg and Hh). Both maternal gene activity and zygotic gene activity are
      required for asymmetric left--right looping of the hindgut. Some of the same
      genes (caudal and brachyenteron) required for embryonic hindgut development also
      act during pupation to construct a new hindgut from imaginal cells. Application
      of the plethora of genetic techniques available in Drosophila, including forward
      genetic screens, should identify additional genes controlling hindgut development
      and thus shed light on a variety of common morphogenetic processes.

PMID- 11846474
TI  - Maintenance of the specification of the anterior definitive endoderm and
      forebrain depends on the axial mesendoderm: a study using HNF3beta/Foxa2
      conditional mutants.
AB  - In mouse embryo, the early induction of the head region depends on signals from
      the anterior visceral endoderm (AVE) and the anterior primitive streak.
      Subsequently, node derivatives, including anterior definitive endoderm and axial
      mesendoderm, are thought to play a role in the maintenance and elaboration of
      anterior neural character. Foxa2 encodes a winged-helix transcription factor
      expressed in signaling centers required for head development, including the AVE,
      anterior primitive streak, anterior definitive endoderm, and axial mesendoderm.
      To address Foxa2 function during formation of the head, we used conditional
      mutants in which Foxa2 function is preserved in extraembryonic tissues during
      early embryonic stages and inactivated in embryonic tissues after the onset of
      gastrulation. In Foxa2 conditional mutants, the anterior neural plate and
      anterior definitive endoderm were initially specified. In contrast, the axial
      mesendoderm failed to differentiate. At later stages, specification of the
      anterior neural plate and anterior definitive endoderm was shown to be labile. As
      a result, head truncations were observed in Foxa2 conditional mutants. Our
      results therefore indicate that anterior definitive endoderm alone is not
      sufficient to maintain anterior head specification and that an interaction
      between the axial mesendoderm and the anterior definitive endoderm is required
      for proper specification of the endoderm. Foxa2 therefore plays an integral role
      in the formation of axial mesendoderm, which is required to maintain the
      specification of the forebrain and the anterior definitive endoderm.

PMID- 11846475
TI  - Coordinated regulation of M phase exit and S phase entry by the Cdc2 activity
      level in the early embryonic cell cycle.
AB  - In the early embryonic cell cycle, exit from M phase is immediately followed by
      entry into S phase without an intervening gap phase. To understand the regulatory
      mechanisms for the cell cycle transition from M to S phase, we examined
      dependence on Cdc2 inactivation of cell-cycle events occurring during the M-S
      transition period, using Xenopus egg extracts in which the extent of Cdc2
      inactivation at M phase exit was quantitatively controlled. The result
      demonstrated that MCM binding to and the initiation of DNA replication of nuclear
      chromatin occurred depending on the decrease of Cdc2 activity to critical levels.
      Similarly, we found that Cdc2 inhibitory phosphorylation and cyclin B degradation
      were turned on and off, respectively, depending on the decrease in Cdc2 activity.
      However, their sensitivity to Cdc2 activity was different, with the turning-on of
      Cdc2 inhibitory phosphorylation occurring at higher Cdc2 activity levels than the
      turning-off of cyclin B degradation. This means that, when cyclin B degradation
      ceases at M phase exit, Cdc2 inhibitory phosphorylation is necessarily activated.
      In the presence of constitutive synthesis of cyclin B, this condition favors the
      occurrence of the Cdc2 inactivation period after M phase exit, thereby ensuring
      progression through S phase. Thus, M phase exit and S phase entry are
      coordinately regulated by the Cdc2 activity level in the early embryonic cell
      cycle.

PMID- 11846476
TI  - Studies on the role of Cux1 in regulation of the onset of joint formation in the
      developing limb.
AB  - Joint formation, the onset of which is characterized by the segmentation of
      continuous skeletal rudiments into two or more separate elements, is a
      fundamental aspect of limb pattern formation, playing a critical role in
      determining the size, shape, and number of individual skeletal elements. Joint
      formation is initiated by conversion of differentiated chondrocytes at sites of
      presumptive joints into densely packed nonchondrogenic cells of the joint
      interzone. This conversion is accompanied by loss of Alcian blue-staining
      cartilage matrix and downregulation of cartilage-specific gene expression. Here,
      we report that Cux1, which encodes a transcription factor containing a
      homeodomain and other DNA-binding motifs, is highly expressed at all of the
      discrete sites of incipient joint formation in the developing limb concomitant
      with conversion of differentiated chondrocytes into interzone tissue. Moreover,
      differentiated limb chondrocytes in micromass cultures infected with a Cux1
      retroviral expression vector are converted into nonchondrogenic cells which
      exhibit loss of Alcian blue cartilage matrix and downregulation of cartilage
      specific gene expression as occurs at the onset of normal joint formation. These
      results suggest that Cux1 is involved in regulating the onset of joint formation
      by facilitating conversion of chondrocytes into nonchondrogenic cells of the
      interzone.

PMID- 11846477
TI  - Acrosome reaction in sperm of the frog, Xenopus laevis: its detection and
      induction by oviductal pars recta secretion.
AB  - Previous electron microscopic observations have shown that the acrosome of the
      sperm of the frog, Xenopus laevis, comprises a membrane-bounded vesicle covering
      the anterior-most position of the head. We obtained a sperm suspension from the
      testes and stained it with LysoSensor Green for observation under a confocal
      laser scanning microscope and found a bright fluorescence reflecting the presence
      of the acrosomes at the top of the sperm head in about 64% of the sperm, with no
      deterioration of their capacity to fertilize. About 40% of the sperm with an
      acrosome underwent an acrosome reaction in response to Ca(2+) ionophore A23187,
      as evidenced by a loss of LysoSensor Green stainability, accompanied by breakdown
      of the acrosomal vesicle. About 53% of the sperm bound to isolated vitelline
      envelopes underwent an acrosome reaction, whereas both jelly water and
      solubilized vitelline envelopes weakly induced an acrosome reaction. When the
      sperm were treated with an oviductal extract obtained from the pars recta, but
      not the pars convoluta region, about 40% of the sperm with acrosomes underwent an
      acrosome reaction. The substance containing acrosome reaction-inducing activity
      in the pars recta extract seemed to be a heat-unstable substance with a molecular
      weight of greater than 10 kDa. The activity was not inhibited by protease
      inhibitors but required extracellular Ca(2+) ions. These results indicate that
      the acrosome reaction occurs on the vitelline envelopes in response to the
      substance deposited from the pars recta during the passage of the oocytes through
      the oviduct.

PMID- 11846478
TI  - Cellular immune response to parasite infection in the Drosophila lymph gland is
      developmentally regulated.
AB  - The mechanisms by which an organism becomes immune competent during its
      development are largely unknown. When infected by eggs of parasitic wasps,
      Drosophila larvae mount a complex cellular immune reaction in which specialized
      host blood cells, lamellocytes and crystal cells, are activated and recruited to
      build a capsule around the parasite egg to block its development. Here, we report
      that parasitization by the wasp Leptopilina boulardi leads to a dramatic increase
      in the number of both lamellocytes and crystal cells in the Drosophila larval
      lymph gland. Furthermore, a limited burst of mitosis follows shortly after
      infection, suggesting that both cell division and differentiation of lymph gland
      hemocytes are required for encapsulation. These changes, observed in the lymph
      glands of third-instar, but never of second-instar hosts, are almost always
      accompanied by dispersal of the anterior lobes themselves. To confirm a link
      between host development and immune competence, we infected mutant hosts in which
      development is blocked during larval or late larval stages. We found that, in
      genetic backgrounds where ecdysone levels are low (ecdysoneless) or ecdysone
      signaling is blocked (nonpupariating allele of the transcription factor broad),
      the encapsulation response is severely compromised. In the third-instar
      ecdysoneless hosts, postinfection mitotic amplification in the lymph glands is
      absent and there is a reduction in crystal cell maturation and postinfection
      circulating lamellocyte concentration. These results suggest that an ecdysone
      activated pathway potentiates precursors of effector cell types to respond to
      parasitization by proliferation and differentiation. We propose that, by
      affecting a specific pool of hematopoietic precursors, this pathway thus confers
      immune capacity to third-instar larvae.

PMID- 11846479
TI  - Bmp activity gradient regulates convergent extension during zebrafish
      gastrulation.
AB  - During vertebrate gastrulation, a ventral to dorsal gradient of bone
      morphogenetic protein (Bmp) activity establishes cell fates. Concomitantly,
      convergent extension movements narrow germ layers mediolaterally while
      lengthening them anteroposteriorly. Here, by measuring movements of cell
      populations in vivo, we reveal the presence of three domains of convergent
      extension movements in zebrafish gastrula. Ventrally, convergence and extension
      movements are absent. Lateral cell populations converge and extend at increasing
      speed until they reach the dorsal domain where convergence speed slows but
      extension remains strong. Using dorsalized and ventralized mutants, we
      demonstrate that these domains are specified by the Bmp activity gradient. In
      vivo cell morphology and behavior analyses indicated that low levels of Bmp
      activity might promote extension with little convergence by allowing mediolateral
      cell elongation and dorsally biased intercalation. Further, single cell movement
      analyses revealed that the high ventral levels of Bmp activity promote epibolic
      migration of cells into the tailbud, increasing tail formation at the expense of
      head and trunk. We show that high Bmp activity limits convergence and extension
      by negatively regulating expression of the wnt11 (silberblick) and wnt5a
      (pipetail) genes, which are required for convergent extension but not cell fate
      specification. Therefore, during vertebrate gastrulation, a single gradient of
      Bmp activity, which specifies cell fates, also regulates the morphogenetic
      process of convergent extension.

PMID- 11846480
TI  - Blocking endogenous FGF-2 activity prevents cranial osteogenesis.
AB  - Normal growth and morphogenesis of the cranial vault reflect a balance between
      cell proliferation in the sutures and osteogenesis at the margins of the cranial
      bones. In the clinical condition craniosynostosis, the sutures fuse prematurely
      as a result of precocious osteogenic differentiation and craniofacial
      malformation results. Mutations in several fibroblast growth factor receptor
      (FGFR) genes have now been identified as being responsible for the major
      craniosynostotic syndromes. We have used a grafting technique to manipulate the
      levels of endogenous FGF-2 ligand in embryonic chick cranial vaults and thereby
      perturb morphogenesis. Implantation of beads loaded with FGF-2 did not affect
      normal cranial development at physiological concentrations, although they
      elicited a morphogenetic response in the limb. Implantation of beads loaded with
      a neutralising antibody to FGF-2 generated a concentration-dependent response.
      When a single bead was implanted, the grafts grew to a massive size as a result
      of increased cell division in the tissue. With greater inactivation of FGF-2
      protein (two to three beads implanted), all further bone differentiation and cell
      proliferation was blocked. These data further support the emerging idea that the
      intensity of FGF-mediated signalling determines the developmental fate of the
      skeletogenic cells in the cranial vault. High and low levels correlate with
      differentiation and proliferation, respectively. A balance between the two
      ensures normal cranial vault morphogenesis. This is consistent with the
      observation that several FGFR mutations causing craniosynostosis result in
      constitutive activation of the receptor.

PMID- 11846481
TI  - Follistatin regulates bone morphogenetic protein-7 (BMP-7) activity to stimulate
      embryonic muscle growth.
AB  - Bone morphogenetic proteins (BMPs) can either promote growth of embryonic muscle
      by expanding the Pax-3-expressing muscle precursor population or restrict its
      development by inducing apoptosis. Follistatin, a proposed BMP antagonist, is
      expressed in embryonic muscle. Deficiency in Follistatin results in muscle
      defects and postnatal asphyxia. Here, we report that during chick limb
      development Follistatin enhances BMP-7 action to induce muscle growth but
      prevents the ability of BMP-7 to induce apoptosis and muscle loss. Follistatin,
      unlike another BMP-binding protein, Noggin, promotes Pax-3 expression and
      transiently delays muscle differentiation and thus exerts proliferative
      signalling during muscle development. We provide data which show that Follistatin
      binds BMP-7 and BMP-2 at low affinities and that the binding is reversible. These
      data suggest that Follistatin acts to present BMPs to myogenic cells at a
      concentration that permits stimulation of embryonic muscle growth.

PMID- 11846482
TI  - Ureteric bud outgrowth in response to RET activation is mediated by
      phosphatidylinositol 3-kinase.
AB  - The c-ret gene encodes a receptor tyrosine kinase (RET) essential for the
      development of the kidney and enteric nervous system. Activation of RET requires
      the secreted neurotrophin GDNF (glial cell line-derived neurotrophic factor) and
      its high affinity receptor, a glycosyl phosphatidylinositol-linked cell surface
      protein GFRalpha1. In the developing kidney, RET, GDNF, and GFRalpha1 are all
      required for directed outgrowth and branching morphogenesis of the ureteric bud
      epithelium. Using MDCK renal epithelial cells as a model system, activation of
      RET induces cell migration, scattering, and formation of filopodia and
      lamellipodia. RET-expressing MDCK cells are able to migrate toward a localized
      source of GDNF. In this report, the intracellular signaling mechanisms regulating
      RET-dependent migration and chemotaxis are examined. Activation of RET resulted
      in increased levels of phosphatidylinositol 3-kinase (PI3K) activity and Akt/PKB
      phosphorylation. This increase in PI3K activity is essential for regulating the
      GDNF response, since the specific inhibitor, LY294002, blocks migration and
      chemotaxis of MDCK cells. Using an in vitro organ culture assay, inhibition of
      PI3K completely blocks the GDNF-dependent outgrowth of ectopic ureter buds. PI3K
      is also essential for branching morphogenesis once the ureteric bud has invaded
      the kidney mesenchyme. The data suggest that activation of RET in the ureteric
      bud epithelium signals through PI3K to control outgrowth and branching
      morphogenesis.

PMID- 11846483
TI  - Effects of L1 blockade on sensory axon outgrowth and pathfinding in the chick
      hindlimb.
AB  - In the developing chick hindlimb, sensory axons, which grow together in bundles
      as they extend distally, and the motoneuron axons they encounter express the cell
      adhesion molecule L1. Following injection of function-blocking anti-L1 antibodies
      into the limb at stage 25, some sensory axons choose inappropriate peripheral
      nerves even though motoneuron pathfinding is unaffected. Here, to further
      elucidate L1's role, we assessed the effects of this perturbation using pathway
      tracing, immune labeling, confocal microscopy, and electron microscopy. After L1
      blockade, sensory axons were still bundled and closely apposed. However, clear
      signs of decreased adhesion were detectable ultrastructurally. Further, sensory
      axons grew into the limb more slowly than normal, wandering more widely,
      branching more frequently, and sometimes extending along inappropriate peripheral
      nerves. Sensory axons that ultimately projected along different cutaneous nerves
      showed increased intermixing in the spinal nerves, due to errors in pathfinding
      and also to a decreased ability to segregate into nerve-specific fascicles. These
      results suggest that, in the highly complex in vivo environment, as in tissue
      culture, L1 stimulates axon growth and enhances fasciculation, and that these
      processes contribute to the orderly, timely, and specific growth of sensory axons
      into the limb.

PMID- 11846484
TI  - DNA methylation at promoter regions regulates the timing of gene activation in
      Xenopus laevis embryos.
AB  - The levels of genomic DNA methylation in vertebrate species display a wide range
      of developmental dynamics. Here, we show that in contrast to mice, the paternal
      genome of the amphibian, Xenopus laevis, is not subjected to active demethylation
      of 5-methyl cytosine immediately after fertilization. High levels of methylation
      in the DNA of both oocyte and sperm are maintained in the early embryo but
      progressively decline during the cleavage stages. As a result, the Xenopus genome
      has its lowest methylation content at the midblastula transition (MBT) and during
      subsequent gastrulation. Between blastula and gastrula stages, we detect a loss
      of methylation at individual Xenopus gene promoters (TFIIIA, Xbra, and c-Myc II)
      that are activated at MBT. No changes are observed in the methylation patterns of
      repeated sequences, genes that are inactive at MBT, or in the coding regions of
      individual genes. In embryos that are depleted of the maintenance
      methyltransferase enzyme (xDnmt1), these developmentally programmed changes in
      promoter methylation are disrupted, which may account for the altered patterns of
      gene expression that occur in these embryos. Our results suggest that DNA
      methylation has a role in regulating the timing of gene activation at MBT in
      Xenopus laevis embryos.

PMID- 11846485
TI  - The Drosophila STAT protein, stat92E, regulates follicle cell differentiation
      during oogenesis.
AB  - Signal transducer and activator of transcription (STAT) proteins are
      transcription factors that play a critical role in the response of a variety of
      eukaryotic cells to cytokine and growth factor signaling. In Drosophila, the STAT
      homolog encoded by the stat92E gene is required for the normal development of
      multiple tissues, including embryonic segmentation, imaginal discs, blood cells,
      male germ cells, and sex determination. We used multiple approaches to study the
      role of stat92E in oogenesis. Stat92E RNA expression is strongest in the
      differentiating follicle cells in the germarium, as determined by in situ
      hybridization. We generated an ethylmethane sulfonate-induced, temperature
      sensitive allele, stat92E(F), in which the mutant protein contains a P506S
      substitution, located in the DNA binding domain. At the restrictive temperature,
      mutant females are sterile. Mutant ovaries have multiple defects, including fused
      egg chambers and an absence of interfollicular stalks cells and functional polar
      follicle cells. An analysis of mosaic clones, using an apparent null stat92E
      allele, indicates that Stat92E is required in the polar/stalk follicle cell
      lineage. We conclude that stat92E is necessary for the early differentiation of
      follicle cells and for proper germ line cell encapsulation during Drosophila
      oogenesis.

PMID- 11846486
TI  - Oviductin, the oviductal protease that mediates gamete interaction by affecting
      the vitelline coat in Bufo japonicus: its molecular cloning and analyses of
      expression and posttranslational activation.
AB  - Previous studies indicated that the acquisition of egg fertilizability during
      transit through the pars recta portion of the oviduct in Bufo japonicus is
      accompanied by hydrolytic conversion of the vitelline coat 40- to 52-kDa
      components to 39-kDa components induced by a 66-kDa serine protease, "oviductin."
      In this study, we cloned a 3028-bp cDNA that contained an open reading frame
      encoding 974 amino acids with a calculated molecular mass of 107.6 kDa, including
      two protease domains and three repeats of CUB domains. Sequence analysis
      indicated that the catalytically active 66-kDa protein comprised an N-terminally
      located oviductin protease and two CUB domains. The oviductin gene was
      transcribed as a part of 6-kb mRNA that was expressed specifically in the cells
      lining the bottom of epithelial folds in the oviductal pars recta, and this
      expression was highly accelerated when the pars recta fragments were cultured in
      the presence of hCG. Western blot analyses using antibodies against a protease
      domain revealed that the catalytically inactive 102-kDa proteins in the pars
      recta granules yield 66-kDa catalytically active and 82- and 59-kDa inactive
      molecules. We propose that the oviductin translated as 107.6-kDa precursors are
      processed both N- and C-terminally to give rise to a 66-kDa active form
      comprising a serine protease and two CUB domains.

PMID- 11846487
TI  - Overgrowth of a mouse model of the Simpson-Golabi-Behmel syndrome is independent
      of IGF signaling.
AB  - The type 1 Simpson-Golabi-Behmel overgrowth syndrome (SGBS1) is caused by loss-of
      function mutations of the X-linked GPC3 gene encoding glypican-3, a cell-surface
      heparan sulfate proteoglycan that apparently plays a negative role in growth
      control by an unknown mechanism. Mice carrying a Gpc3 gene knockout exhibited
      several phenotypic features that resemble clinical hallmarks of SGBS1, including
      somatic overgrowth, renal dysplasia, accessory spleens, polydactyly, and
      placentomegaly. In Gpc3/DeltaH19 double mutants (lacking GPC3 and also carrying a
      deletion around the H19 gene region that causes bialellic expression of the
      closely linked Igf2 gene by imprint relaxation), the Gpc3-null phenotype was
      exacerbated, while additional SGBS1 features (omphalocele and skeletal defects)
      were manifested. However, results from a detailed comparative analysis of growth
      patterns in double mutants lacking GPC3 and also IGF2, IGF1, or the type 1 IGF
      receptor (IGF1R) provided conclusive genetic evidence inconsistent with the
      hypothesis that GPC3 acts as a growth suppressor by sequestering or
      downregulating an IGF ligand. Nevertheless, our data are compatible with a model
      positing that there is downstream convergence of the independent signaling
      pathways in which either IGFs or (indirectly) GPC3 participate.

PMID- 11846488
TI  - Inflammation, infection, and coronary heart disease.

PMID- 11846489
TI  - Tumour necrosis factor-alpha, inflammatory biomarkers, and atherogenesis.

PMID- 11846490
TI  - Is time the overriding factor in thrombolytic therapy?

PMID- 11846491
TI  - Vulnerable plaques: let's stop sinking on submerged icebergs?

PMID- 11846492
TI  - Can catheter ablation cure post-infarction ventricular tachycardia?

PMID- 11846493
TI  - The problem of chronic refractory angina; report from the ESC Joint Study Group
      on the Treatment of Refractory Angina.

PMID- 11846494
TI  - Chlamydia pneumoniae IgA titres and coronary heart disease; prospective study and
      meta-analysis.
AB  - AIMS: To examine associations between Chlamydia pneumoniae IgA titres and
      incident coronary heart disease, and to compare them with associations previously
      reported between C. pneumoniae IgG titres and coronary heart disease. METHODS AND
      RESULTS: We measured serum concentrations of C. pneumoniae IgA antibodies in 502
      coronary heart disease cases and in 1005 age- and town-matched controls 'nested'
      in a community-based prospective study of 5661 British men (mean follow-up in
      controls, 16 years), and conducted a meta-analysis of published prospective
      studies to place our findings in context. Two hundred and twenty-one (44%) of the
      cases were in the top third of C. pneumoniae IgA titres compared with 336 (33%)
      of the controls, yielding an odds ratio for coronary heart disease of 1.84 (95%
      confidence interval 1.40-2.43) which was largely unchanged after adjustment. In
      aggregate, the present study and nine previously reported prospective studies of
      C. pneumoniae IgA titres involved 2283 cases, yielding a combined odds ratio for
      coronary heart disease of 1.25 (1.03-1.53), with no significant heterogeneity
      among the ten studies (chi(2)9=7.8; P>0.1). This combined odds ratio is
      compatible with that previously reported for C. pneumoniae IgG titres and
      coronary heart disease (1.15, 0.97-1.36). CONCLUSION: Neither C. pneumoniae IgA
      titres nor IgG titres are strongly predictive of coronary heart disease in the
      general population.

PMID- 11846495
TI  - Plasma tumour necrosis factor-alpha and early carotid atherosclerosis in healthy
      middle-aged men.
AB  - AIMS: Tumour necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine,
      which is implicated in some metabolic disorders and may play a role in the
      development of cardiovascular disease. We examined whether plasma TNF-alpha is
      related to established cardiovascular risk indicators, plasma levels of soluble
      cellular adhesion molecules and carotid artery intima-media thickness determined
      by ultrasound examination in a population-based cohort of 96 healthy 50-year-old
      men. METHODS AND RESULTS: TNF-alpha and cellular adhesion molecules were measured
      with enzyme-linked immunosorbent assays. Plasma TNF-alpha concentration was
      associated with systolic and diastolic blood pressure, degrees of alimentary
      lipaemia, plasma very low density lipoprotein triglyceride, low density
      lipoprotein (LDL) cholesterol concentrations and peak LDL particle size. Two
      indices of insulin resistance as well as all soluble cellular adhesion molecules
      correlated positively with TNF-alpha. The plasma TNF-alpha concentration was
      associated with common carotid intima-media thickness in univariate analysis. In
      contrast, soluble E-selectin and postprandial triglycerides, but not TNF-alpha,
      were independent determinants of common carotid intima--media thickness.
      CONCLUSION: The plasma TNF-alpha concentration is associated with degrees of
      early atherosclerosis and correlates with metabolic and cellular perturbations
      that are considered important for the vascular process.

PMID- 11846496
TI  - Evolution of all-causes and cardiovascular mortality in the age-group 75-84 years
      in Europe during the period 1970-1996; a comparison with worldwide changes.
AB  - BACKGROUND: In spite of the increase in longevity in the past century, studies of
      mortality patterns in elderly populations are scarce. We investigated
      cardiovascular and all-cause mortality patterns in age-group 75-84 years in
      Europe in the period 1970-1996. Methods Mortality data for the age-group 75-84
      years were obtained from WHO and standardized according to the old European
      population standard. Tables were produced showing mortality rates per country
      around the year 1995 and trends were calculated over the period 1970-1996 using
      linear regression analysis. Results In both men and women aged 75-84 all-cause
      and cardiovascular mortality rates were higher in Central and Eastern Europe
      compared with Western Europe. For the last 3 available years, all-cause mortality
      rates differed by a factor 2/2.5 (men, women) when comparing the country with the
      highest with that of the lowest rate. For total cardiovascular mortality this
      factor was about 4/5 (men, women). During the period 1970-1996, all-cause and
      total cardiovascular mortality rates declined in most European countries. The
      decline in all causes of mortality was almost exclusively due to a decline in
      total cardiovascular disease mortality, especially stroke. Increases in total
      cardiovascular mortality were observed in some central European countries and
      Greece. CONCLUSION: Major changes, mainly a decline, occurred in all-cause and
      cardiovascular mortality in subjects aged 75-84 in Europe. Therefore a passive
      attitude to health problems in the elderly is not warranted.

PMID- 11846497
TI  - Usefulness of the presenting electrocardiogram in predicting myocardial salvage
      with thrombolytic therapy in patients with a first acute myocardial infarction.
AB  - AIMS: Patients with Q waves and T-wave inversion are generally at a later stage
      of the infarction process than patients without these changes. Our aim was to
      investigate whether a single assessment of electrocardiographic parameters at
      presentation would predict the proportion of myocardium salvageable by
      thrombolytic therapy. METHODS AND RESULTS: Electrocardiographic algorithms to
      calculate the potential and final infarct size have been developed and allow the
      proportion of myocardium salvageable with therapy to be calculated. This was
      measured in 146 patients with acute myocardial infarction who had angiography at
      a median of 91 min after streptokinase. The relationship between myocardial
      salvage and the electrocardiographic parameters at presentation (Q waves, T-wave
      inversion, quantitative ST segment changes, and the initial QRS score), was
      examined together with the 90-min angiographic parameters (TIMI flow grade and
      collateral grade), clinical parameters (haemodynamics and age), and time to
      therapy. Parameters that correlated with myocardial salvage included the initial
      QRS score (r=-0.56, P<0.0001), Q wave grade (r=-0.36, P<0.0001), number of leads
      with ST depression (r=0.28, P<0.001), maximum ST depression (r=0.27, P<0.01), T
      inversion grade (r=-0.26, P<0.01), and TIMI flow grade at 90 min (r=0.21,
      P<0.02). The time from symptom onset to thrombolytic therapy did not correlate
      with salvage (r=-0.09). On multivariate analysis, only the initial QRS score and
      T-inversion grade on the initial electrocardiogram were independent predictors of
      salvage (multivariate r using both variables combined=0.57, P<0.001).
      CONCLUSIONS: The QRS score and T-wave inversion grade on the presenting
      electrocardiogram provide important information in predicting myocardial salvage.
      These parameters may help triage patients to appropriate therapies.

PMID- 11846498
TI  - Morphological and mechanical information of coronary arteries obtained with
      intravascular elastography; feasibility study in vivo.
AB  - AIMS: Plaque composition is a major determinant of coronary related clinical
      syndromes. In vitro experiments on human coronary and femoral arteries have
      demonstrated that different plaque types were detectable with intravascular
      ultrasound elastography. The aim of this study was to investigate the feasibility
      of applying intravascular elastography during interventional catheterization
      procedures. METHODS AND RESULTS: Data were acquired in patients (n=12) during
      PTCA procedures with an EndoSonics InVision echoapparatus equipped with
      radiofrequency output. The systemic pressure was used to strain the tissue, and
      the strain was determined using cross-correlation analysis of sequential frames.
      A likelihood function was determined to obtain the frames with minimal motion of
      the catheter in the lumen, since motion of the catheter prevents reliable strain
      estimation. Minimal motion was observed near end-diastole. Reproducible strain
      estimates were obtained within one pressure cycle and over several pressure
      cycles. Validation of the results was limited to the information provided by the
      echogram. Strain in calcified material (0.20%+/-0.07) was lower (P<0.001) than in
      non-calcified tissue (0.51%+/-0.20). CONCLUSION: In vivo intravascular
      elastography is feasible. Significantly higher strain values were found in non
      calcified plaques than in calcified plaques.

PMID- 11846499
TI  - Catheter ablation and antiarrhythmic drugs for haemodynamically tolerated post
      infarction ventricular tachycardia; long-term outcome in relation to acute
      electrophysiological findings.
AB  - AIMS: Radiofrequency catheter ablation is effective at terminating ventricular
      tachycardia, but the overall clinical role of the technique in patients with a
      prior myocardial infarction is still debated, due to the uncertainties of the
      long-term reliability of the procedure. The purpose of this study was to
      prospectively investigate the relationship between acute results obtained by
      catheter ablation and long-term outcome in a homogeneous population of patients
      with post-myocardial infarction ventricular tachycardia. METHODS AND RESULTS: One
      hundred and twenty-four consecutive patients with recurrent, drug-refractory,
      haemodynamically tolerated ventricular tachycardia were included in the study.
      This population accounted for 30% of the patients with post-myocardial infarction
      ventricular tachycardia admitted between April 1992 and September 1997 to the
      investigating centres. The ablation was successful in eliminating sustained
      ventricular tachycardia in 91 of them (73%); a partial result was obtained in 21
      (17%) and failure in 12 (10%). Low dose amiodarone and/or beta-blockers were
      maintained in 86% of the patients. Over a median follow-up of 41.5 months
      (interquartile range 30.5-59.5 months), there were 15 deaths (12%), three of
      which were sudden (2.4%); the 12 remaining patients died of heart failure. Event
      free survival analysis showed a significantly lower ventricular tachycardia
      recurrence rate in patients with a successful procedure as compared to those with
      failure or a partial result (19% vs 53% at one year and 27% vs 60% at 3 years,
      P=0.003). A repeat procedure was performed in 15 patients with early recurrences
      and was followed in all by long-term success. Of those who submitted to a second
      procedure, 93/124 patients (75%) are free of ventricular tachycardia recurrences.
      An implantable cardioverter-defibrillator (ICD), following procedure failure, was
      implanted in 13 patients (11%) of the study population. CONCLUSIONS:
      Radiofrequency catheter ablation is effective in a wide population of patients
      with recurrent tolerated ventricular tachycardia, with very low sudden death and
      cardiac mortality rates over the long-term. Persistent ventricular tachycardia
      inducibility after catheter ablation requires an ICD implant and/or repeat
      ablation.

PMID- 11846500
TI  - Broadening the real world of health care: what we can do for heart failure
      patients.

PMID- 11846501
TI  - Chronic heart failure guidelines.

PMID- 11846503
TI  - Beta-blockers in chronic heart failure.

PMID- 11846506
TI  - Regulation of lacrimal gland secretion by neurotransmitters and the EGF family of
      growth factors.

PMID- 11846507
TI  - Transforming growth factor beta in experimentally detached retina and periretinal
      membranes.
AB  - This study was undertaken to determine whether experimental retinal detachment
      produces changes in retinal localization of three isoforms of transforming growth
      factor beta (TGF-beta) and the type II receptor for this protein. Neural retinas
      of young adult cats were detached from the pigment epithelium. Survival times
      varied from 3 to 28 days to study the temporal course of TGF-beta localization
      during retinal degeneration. ELISA assay for TGF-beta1 and -beta2 was performed
      on samples of fluid from the vitreous chamber to determine whether active or
      inactive TGF-beta was present. Confocal microscopy was used to localize TGF
      beta1, -beta2 and -beta3 and the type II TGF-beta receptor at the various
      detachment durations. Following experimental retinal detachment the levels of TGF
      beta2 increased in the vitreous chamber but no changes in TGF-beta1 were
      detected. Levels were increased 3 days post-detachment and continued throughout
      the 28 day period studied. The most prominent changes in immunolocalization
      occurred in the TGF-beta1 and -beta2 isoforms. Increased immunolabeling was seen
      in Muller cells and ganglion cell bodies. Hypertrophied Muller cell processes
      formed periretinal membranes that were heavily labeled by the TGF-beta2 antibody.
      Some increased immunostaining for TGF-beta3 was observed in the ganglion cell
      bodies. Labeling for the TGF-beta type II receptor was seen in Muller cells,
      ganglion cells and the inner and outer plexiform layers in both normal and
      detached retinas. Changes in localization of the receptor after detachment
      paralleled the changes seen in TGF-beta protein localization. These results
      demonstrate that retinal detachment induces the synthesis and secretion of TGF
      beta2. Growth factor and receptor immunolabeling were increased in Muller cells
      suggesting that this isoform is involved in the retinal gliotic response and may
      contribute to the development of proliferative vitreoretinopathy.

PMID- 11846508
TI  - Role of transforming growth factor-beta1 and its latent form binding protein in
      pseudoexfoliation syndrome.
AB  - Pseudoexfoliation (PEX) syndrome is a common and clinically important systemic
      condition characterized by the pathologic production and accumulation of an
      abnormal fibrillar extracellular material in many intra- and extraocular tissues.
      Recent evidence suggests that it is a type of elastosis associated with the
      excess synthesis of elastic microfibrillar components such as fibrillin-1. Since
      transforming growth factor (TGF)-beta is a major modulator of extracellular
      matrix formation, the potential involvement of TGF-beta and its latent form
      binding protein (LTBP) in this aberrant matrix process was investigated. The
      expression of various isoforms of TGF-beta and LTBP was investigated in the
      anterior segment tissues of PEX and control eyes on the protein and mRNA level by
      light and electron microscopic immunohistochemistry, in situ hybridization, and
      semiquantitative RT-PCR. TGF-beta1 and TGF-beta2 levels were measured in aqueous
      humor and serum of PEX and control patients by ELISA. Cultures of Tenon's capsule
      fibroblasts were established to study the effect of TGF-beta1 on fibrillin-1 mRNA
      expression by Northern blot analysis. Significantly increased concentrations of
      both total and active TGF-beta1 were measured in the aqueous humor of PEX eyes
      without and with glaucoma as compared to control eyes, whereas levels of TGF
      beta2 were not significantly different. The expression of TGF-beta1, LTBP-1, and
      LTBP-2, but not TGF-beta2, was markedly increased in anterior segment tissues of
      PEX eyes, particularly in the non-pigmented epithelium of the ciliary body, on
      both the mRNA and the protein level. Latent TGF-beta1 staining was consistently
      associated with PEX material deposits and could be released by proteolytic
      processing. Double immunolabeling revealed clear co-localization of LTBP-1 and -2
      with latent TGF-beta1 and with fibrillin-1 on PEX fibrils. The expression of mRNA
      coding for fibrillin-1 was up-regulated in vitro by TGF-beta1. This study
      provides evidence for a significant role of TGF-beta1 and the LTBPs 1 and 2 in
      PEX syndrome. The results suggest that increased levels of latent and active TGF
      beta1 in the aqueous humor of PEX patients, derived from enhanced local synthesis
      and activation, promote the buildup of the abnormal extracellular elastic
      material characteristic of PEX syndrome. They further support a dual role for
      LTBPs, both as integral structural components of PEX fibers and as a means of
      matrix anchorage of latent TGF-beta1, representing one possible mechanism for the
      regulation of TGF-beta1 activity in PEX eyes. Future therapeutic strategies might
      focus on TGF-beta1 antagonistic approaches.

PMID- 11846509
TI  - The induction/impact tonometer: a new instrument to measure intraocular pressure
      in the rat.
AB  - Non-invasive intraocular pressure (IOP) measurement in rats can be performed with
      a variety of methods, none of which seems appropriate for scaling down for the
      mouse eye. In an attempt to develop such a method for non-invasive IOP
      measurement in mice, an alternative concept, that of rebound tonometry, was
      explored using an induction/impact (I/I) tonometer probe. IOP measurement using
      the rebound concept is based on bouncing a probe onto the eye and detecting its
      motion. Motion parameters of the probe, which vary according to eye pressure, are
      used to calculate the IOP. As a first step towards this goal a prototype I/I
      tonometer was evaluated for IOP measurement of the rat eye. Two similar
      instruments were constructed and tested for their ability to measure accurately
      and reliably rat IOP by comparing the measurements against the manometric (true)
      IOP as determined by cannulation ex vivo. Good correlation between the true IOP
      and the I/I measurements (R(2) = 0.95) was detected for IOP between 7.4 and 56
      mmHg. Although individual eyes tested showed some variability in the relationship
      of the measured IOP with the true IOP, this variability was minimal. Starting
      probe-cornea distance between 3 and 5 mm, and angle of impact up to 25 degrees
      relative to the visual axis at the corneal apex, did not affect the
      reproducibility of the I/I tonometer. Comparison of I/I tonometer measurements to
      direct manometric determination of IOP by in vivo cannulation of eyes in
      anesthetized normal female Wistar rats correlated reasonably well (R(2) = 0.67)
      with manometrically determined IOP within the narrow range of normal rat IOPs (10
      16.5 mmHg), underestimating the true (manometric) IOP by an average of 11.6%. The
      I/I tonometer is a reliable and accurate instrument for non-invasive IOP
      measurement in rat eyes that can potentially be adapted for IOP measurement in
      mice.

PMID- 11846511
TI  - Migration mechanisms: corneal epithelial tissue and dissociated cells.
AB  - The migratory mechanism of intact bovine corneal epithelial tissue and individual
      corneal epithelial cells over synthetic surfaces in vitro were compared. In
      migrating tissue, adhesion between component cells was demonstrated by
      immunostaining for desmoplakin and identification of desmosomes by electron
      microscopy. The apparent intermeshing of microtubules within the tissue and
      interdigitation of cytoplasmic membranes showed the close association of cells.
      Portions of the advancing edge of the tissue contained actin filaments that were
      orientated parallel to the leading tissue front. These filaments appeared to span
      adjacent cells suggesting that migration partially involved the contraction of
      the actin cable, similar to the 'purse-string' mechanism originally identified in
      the closure of fetal skin wounds. Intact actin filaments and microtubules were
      necessary to maintain optimum migration rates for tissue and cells. However,
      tissue morphology was not dependent on microtubule integrity. During the
      migration of individual epithelial cells, no staining for desmoplakin was
      observed and there were clear divisions between the microtubules of adjacent
      cells. Actin filaments tended to be arranged parallel to the direction of cell
      movement.Therefore, migration of epithelial tissue sheets over synthetic surfaces
      occurs by mechanisms that differ from the migration of individual epithelial
      cells. Model systems based on the migration of intact tissue would give a more
      realistic assessment of the suitability of a material for biomaterial
      applications than the use of separate epithelial cells.

PMID- 11846510
TI  - Presence and structure of innervated myotendinous cylinders in rabbit extraocular
      muscle.
AB  - Innervated myotendinous cylinders (IMCs) in rabbit extraocular muscles (EOMs)
      were identified for the first time. The nature of IMC nerve terminals was
      demonstrated by means of electron microscopy and double fluorescent staining. The
      distal EOM portions of four rabbits of different age and sex were prepared for
      transmission electron microscopy and for double-fluorescent labelling. Antibody
      against neurofilament H and alpha-bungarotoxin were applied on longitudinal
      cryostat sections of distal myotendinous junction. IMCs were consistently and
      frequently observed at the distal myotendons of each EOM. More than 30 IMCs were
      counted in two medial recti of a 6 month and 3 year old rabbit. IMCs were
      enveloped by two to three layered capsules of fibrocytes. Each IMC contained the
      terminal portion of one multiply-innervated muscle fibre and its corresponding
      tendon. The tendon compartment of an IMC was entered by a single myelinated nerve
      fibre (2-3 microm in diameter). Inside the IMC, this nerve fibre ramified into up
      to four preterminal branches. Nerve terminals exclusively established contacts
      with the muscle fibre at its junction with the tendon fibrils. Nerve terminals
      contained mitochondria and a multitude of clear vesicles. Within the synaptic
      cleft a basal lamina was always present. alpha-Bungarotoxin labelled the muscle
      side of these myoneural contacts. Nerve terminals exhibited neither age nor sex
      differences. Among all species so far investigated, rabbit IMCs are unique by
      exhibiting exclusively myoneural terminal contacts. Based on fine structure and
      alpha-bungarotoxin binding, myoneural contacts in rabbit IMCs are almost
      certainly motor, as previously observed only in human IMCs. Thus, rabbit IMCs are
      supposed to have a predominant effector function.

PMID- 11846512
TI  - Ocular hypotensive and aqueous outflow-enhancing effects of AL-3037A (sodium
      ferri ethylenediaminetetraacetate).
AB  - AL-3037A (Sodium ferri ethylenediaminetetraacetate), a novel compound shown to
      stimulate the degradation of glycosaminoglycans, was evaluated for its effects on
      aqueous humor outflow and intraocular pressure (IOP) in four experimental models.
      Its effect on outflow facility was assessed in bovine and human ocular perfusion
      organ cultures. Its IOP effect was tested in normotensive and dexamethasone
      induced ocular hypertensive rabbits. In bovine eyes, perfusion with AL-3037A
      (0.1% w/v, 2.3 m M) significantly increased the outflow facility well above the
      normal 'wash-out' effect. At 30 min after perfusion, the outflow facility of drug
      treated eyes increased by 26.0+/-2.8% (mean +/- S.E.(M.), n = 8), significantly
      higher than the 12.1 +/- 2.8% increase in vehicle-treated eyes. This difference
      sustained throughout the study period (2 hr). The compound also enhanced aqueous
      outflow in perfused human anterior segments. In non-glaucomatous eyes, it
      produced a small decrease in IOP (15.4 +/- 4.6%, n = 17), but in tissues derived
      from glaucoma patients, bolus administration of 3 mg (7 micromol) of AL-3037A
      lowered the IOP by 52-68% (n = 2) lasting for at least 3 hr. This outflow
      enhancing effect of AL-3037A in ex vivo studies was confirmed by in vivo results.
      In normotensive rabbits, oral (50 mg kg(-1)), intravenous (10 mg kg(-1)), or
      topical (2 mg; 50 microl of 4% w/v solution) administration of AL-3037A produced
      maximum reduction of IOP, when compared to vehicle-treated animals, by 34.7+/
      3.5% (n = 10), 22.0 +/- 4.6% (n = 10), and 21.6 +/-4.5% (n = 10), respectively.
      In dexamethasone induced ocular hypertensive rabbits, topical application of the
      compound (0.5 mg; 25 microl of 2% w/v solution) reduced IOP significantly by
      19.2+/- 0.4% (n = 7) at 3 hr after dosing. Importantly, the IOP lowering effect
      of AL-3037A did not diminish even after repeated treatments in consecutive days.
      Thus, in the four study models across three animal species, AL-3037A was
      demonstrated to be an efficacious ocular hypotensive compound whose effect is
      most likely mediated by augmentation of the aqueous outflow. Its proposed action
      on the metabolism of glycosaminoglycans may provide a new and unique mechanism
      for the treatment of glaucoma.

PMID- 11846513
TI  - Ubiquitin-activating enzyme (E1) isoforms in lens epithelial cells: origin of
      translation, E2 specificity and cellular localization determined with novel site
      specific antibodies.
AB  - Lens development and response to peroxide stress are associated with dramatic
      changes in protein ubiquitination, reflecting dynamic changes in activity of the
      ubiquitin-activating enzyme (E1). Two isoforms of E1 (E1A and E1B) have been
      identified in lens cells although only one E1 mRNA, containing three potential
      translational start sites, has been detected. Novel, site-specific antibodies to
      E1 were generated and the hypothesis that the two isoforms of E1 are translated
      from alternative initiation codons of a single mRNA was tested. Antibodies raised
      against E1A-N peptide (Met(1)to Cys(23)of E1A) reacted only with E1A by
      immunoblot and immunoprecipitation. Antibodies raised against E1B-N peptide
      (Met(1)to Glu(25)of E1B or Met(41)to Glu(65)of E1A) and E1AB-C peptide
      (His(1030)to Arg(1058)of E1A or His(990)to Arg(1018)of E1B) reacted with both E1A
      and E1B. These results indicate that (1) E1A and E1B contain the same C-terminal
      residues; (2) E1A contains the N terminal sequence of E1B; and (3) E1B does not
      contain the N terminal sequence of E1A. The two isoforms of lens E1 are therefore
      translated from a single mRNA. Specifically, E1A is translated from the first
      initiation codon, and E1B translated from the second initiation codon. E1A and
      E1B were affinity-purified, and their ability to 'charge' ubiquitin carrier
      proteins (E2s) with activated ubiquitin was compared in a cell-free system. E1A
      and E1B were indistinguishable with respect to charging different E2s. However,
      E1 immunolocalization studies with human lens epithelial cells indicate that E1A
      and E1B are preferentially localized to the nucleus and cytosol, respectively.
      This observation suggests that E1A and E1B ubiquitinate different proteins and
      serve different functions in intact cells.

PMID- 11846514
TI  - Identification of novel molecular components of the photoreceptor connecting
      cilium by immunoscreens.
AB  - The connecting cilium of photoreceptor cells is the only intracellular link
      between the morphologically, functionally and biochemically different
      compartments of the inner and outer segments. The non-motile modified cilium
      plays an important role in the organization and the function of photoreceptor
      cells, namely in delivery and turnover of enzymes and substrates of the visual
      transduction cascade, and the photosensitive membranes of the outer segment. The
      protein components of the cilium participate in the intracellular transport
      through the cilium, in the outer segment disk morphogenesis and in the
      maintenance of discrete membrane domains. In order to identify yet unknown
      cytoskeletal components of the connecting cilium, a combined biochemical and
      molecular biological strategy was applied. For this purpose, antibodies were
      raised against proteins of photoreceptor cell axonemes. Using this AX-4
      antiserum, a rat retina cDNA expression library was immunoscreened and clones
      encoding partial sequences of (i) already known photoreceptor specific proteins;
      (ii) ubiquitously expressed proteins; (iii) clones with homologies to retinal
      ESTs; and (iv) clones coding for cytoskeletal proteins were isolated. Further
      analysis revealed that these candidate clones have homologies to Drosophila
      flightless I, mouse APC-binding protein EB2, human microtubule associated protein
      4 (MAP4), human centrin 3, human cytoplasmic dynein intermediate chain 2C, and
      human dynamitin.The immunoscreening approach used here was successfully applied
      to isolate genes encoding yet unknown cytoskeletal proteins of photoreceptor cell
      axonemes. The obtained information will provide further insight into the role of
      the connecting cilium in photoreceptor cell function.

PMID- 11846515
TI  - Measurement of TIMP-3 expression and Bruch's membrane thickness in human macula.
AB  - An increase or accumulation in tissue inhibitor of matrix metalloproteinases-3
      (TIMP-3) protein in Bruch's membrane with ageing in normal eyes, and in age
      related macular degeneration (AMD) has been previously demonstrated. The purpose
      of this study was to determine whether the expression of TIMP-3 mRNA increases
      with age, and to define any relationship between altered expression and Bruch's
      membrane thickness. Normal eyes were obtained from 30 donors (age range 15-90
      years). Full-thickness 8 mm macular punches centred on the fovea were taken to
      allow removal of the chorioretinal complex, for subsequent nucleic acid
      extraction. Samples were normalized for RNA degradation using beta-actin reverse
      transcriptase-polymerase chain reaction (RT-PCR). A competitive RT-PCR was then
      used to allow measurement of TIMP-3 gene expression in each sample. The tissue
      adjacent to that used for nucleic acid extraction was processed histologically to
      allow determination of Bruch's membrane thickness. Bruch's membrane thickness was
      found to increase with age (P < 0.01), but TIMP-3 expression, as measured by
      competitive RT-PCR, was not significantly increased with age (P = 0.19). An
      inverse correlation was noted between TIMP-3 expression and Bruch's membrane
      thickness after controlling for age (P = 0.032). The results of this study
      suggest that TIMP-3 expression does not alter significantly with age. Therefore,
      accumulation of the TIMP-3 protein must occur by a mechanism other than increased
      expression. TIMP-3 protein levels may still prove to contribute to events
      associated with ageing in the macula, such as matrix remodelling in Bruch's
      membrane. Further studies are required to elucidate the precise interactions and
      turnover of the TIMP-3 protein, and resulting changes in the control of matrix
      metalloproteinase activity in the ageing macula.

PMID- 11846516
TI  - Quantitative molecular characterization of bovine vitreous and lens with non
      invasive dynamic light scattering.
AB  - The non-invasive technique of dynamic light scattering (DLS) was used to
      quantitatively characterize vitreous and lens structure on a molecular level by
      measuring the sizes of the predominant particles and mapping the three
      dimensional topographic distribution of these structural macromolecules in three
      spatial dimensions. The results of DLS measurements in five fresh adult bovine
      eyes were compared to DLS measurements in model solutions of hyaluronan (HA) and
      collagen (Coll). In the bovine eyes DLS measurements were obtained from excised
      samples of gel and liquid vitreous and compared to the model solutions.
      Measurements in whole vitreous were obtained at multiple points posterior to the
      lens to generate a three-dimensional 'map' of molecular structure. The
      macromolecule distribution in bovine lens was similarly characterized.In each
      bovine vitreous (Bo Vit) specimen, DLS predominantly detected two distinct
      particles, which differed in diffusion properties and hence size. Comparisons
      with model vitreous solutions demonstrated that these most likely corresponded to
      the Coll and HA components of vitreous. Three-dimensional mapping of Bo Vit found
      heterogeneity throughout the vitreous body, with different particle size
      distributions for Coll and HA at different loci. In contrast, the three
      dimensional distribution of lens macromolecules was more homogeneous. Thus, the
      non-invasive DLS technique can quantitate the average sizes of vitreous and lens
      macromolecules and map their three-dimensional distribution. This method to
      assess quantitatively the macromolecular structure of vitreous and lens should be
      useful for clinical as well as experimental applications in health and disease.

PMID- 11846517
TI  - Characterization of a mutation in the lens-specific MP70 encoding gene of the
      mouse leading to a dominant cataract.
AB  - During an ethylnitrosourea mutagenesis screen, Aey5, a new mouse mutation
      exhibiting an autosomal dominant congenital cataract was isolated. The
      cataractous phenotype is visible at the eye opening and progresses to a nuclear
      and zonular cataract at 2 months of age with no difference in onset or severity
      between heterozygous and homozygous mutants. Histological analysis revealed that
      fiber cell differentiation continues at the lens bow region, but the cell nuclei
      do not degrade normally and remain in the deeper cortex. Further, the lens
      nucleus has clefts of various sizes while the remainder of the eye was
      morphologically normal. The mutation was mapped to chromosome 3 between the
      markers D3Mit101 and D3Mit77 near the connexin encoding genes Gja5 and Gja8.
      Sequence analysis revealed no differences in the Gja5 gene, but identified a T-
      >C mutation at position 191 in the Gja8 gene, which was confirmed by an
      additional Mva 12691 restriction site in the genomic DNA of homozygous mutants.
      This mutation results in Val-->Ala substitution at codon 64 of connexin50 (Cx50)
      also known as lens membrane protein 70 (MP70). Aey5 represents the second
      dominant mouse cataract mutant affecting Cx50, a membrane protein preferentially
      expressed in the lens. Since both mutations affect similar regions in the first
      extracellular domain this region appears to be critically important for its
      function in lens transparency.

PMID- 11846518
TI  - Visual function in patients with cone-rod dystrophy (CRD) associated with
      mutations in the ABCA4(ABCR) gene.
AB  - Mutations in the ABCA4(ABCR) gene cause autosomal recessive Stargardt disease
      (STGD). ABCR mutations were identified in patients with cone-rod dystrophy (CRD)
      and retinitis pigmentosa (RP) by direct sequencing of all 50 exons in 40
      patients. Of 10 patients with RP, one contained two ABCR mutations suggesting a
      compound heterozygote. This patient had a characteristic fundus appearance with
      attenuated vessels, pale disks and bone-spicule pigmentation. Rod
      electroretinograms (ERGs) were non-detectable, cone ERGs were greatly reduced in
      amplitude and delayed in implicit time, and visual fields were constricted to 10
      degrees diameter. Eleven of 30 (37%) patients with CRD had mutations in ABCR. In
      general, these patients showed reduced but detectable rod ERG responses, reduced
      and delayed cone responses, and poor visual acuity. Rod photoresponses to high
      intensity flashes were of reduced maximum amplitude but showed normal values for
      the gain of phototransduction. Most CRD patients with mutations in ABCR showed
      delayed recovery of sensitivity (dark adaptation) following exposure to bright
      light. Pupils were also significantly smaller in these patients compared to
      controls at 30 min following light exposure, consistent with a persistent
      'equivalent light' background due to the accumulation of a tentatively identified
      'noisy' photoproduct.

PMID- 11846520
TI  - Elevation of lactic acid concentration associated with megalophthalmia in Black
      Moor goldfish.

PMID- 11846519
TI  - Complement activation and inflammatory processes in Drusen formation and age
      related macular degeneration.
AB  - Recent studies implicate inflammation and complement mediated attack as early
      events in drusen biogenesis. The investigations described here sought to
      determine whether primary sites of complement activation could be identified
      within drusen substructure, and whether known inhibitors of the terminal pathway
      of complement are present in drusen and/or retinal pigmented epithelial (RPE)
      cells that lie in close proximity to drusen. Immunohistochemical examination
      shows two fluid phase regulators of the terminal pathway, vitronectin (Vn, S
      protein) and clusterin (apolipoprotein J), to be present in drusen; Vn also
      accumulates in the cytoplasm of RPE cells that are closely associated with
      drusen. The membrane associated complement inhibitor, complement receptor 1, is
      also localized in drusen, but it is not detected in RPE cells
      immunohistochemically. In contrast, a second membrane associated complement
      inhibitor, membrane cofactor protein, is present in drusen associated RPE cells,
      as well as in small, spherical substructural elements within drusen. These
      previously unidentified elements also show strong immunoreactivity for
      proteolytic fragments of complement component C3 that are characteristically
      deposited at sites of complement activation. It is proposed that these structures
      represent residual debris from degenerating RPE cells that are the targets of
      complement attack. It is likely that RPE cell debris entrapped between the RPE
      monolayer and Bruch's membrane serves as a chronic inflammatory stimulus and a
      potential nucleation site for drusen formation. Thus, the process of drusen
      biogenesis may be envisaged as a secondary manifestation of primary RPE pathology
      that is exacerbated by consequences of local inflammatory processes.

PMID- 11846521
TI  - Plasmodium falciparum: underestimation of dihydrofolate reductase and
      dihydropteroate synthase polymorphism in field samples: a technical shortcoming
      of nested PCR assays with mutation-specific primers.
AB  - n a study parallel to the present one, we conducted a genotype characterization
      of Plasmodium falciparum based on isolates of patients infected with malaria, who
      come from a small location in Colombia. The analysis involved extraction of DNA
      from hematological smears, amplification of the dihydrofolate reductase gene and
      the dihydropteroate synthase (DHPS) gene for each sample by PCR, and detection
      through mutation-specific primers nested PCR of mutations associated with
      resistance to pyrimethamine and sulfadoxine. Given the difficulty in quantifying
      the DNA extracts due to the type of sample and its heterogeneity, different
      volumes of the product of the first PCR were tested as template for the nested
      PCR. Surprisingly, for some samples, we found contradictory results between
      determinations, which differed only in the amount of template used. This prompted
      a more general concern that in a natural isolate, where the parasite population
      is heterogeneous, the nested PCR with mutation-specific primers technique can
      produce erroneous results that underestimate the complexity of the sample. To
      test this hypothesis, we designed experiments in this study using position 581 of
      the DHPS gene as an indicator system and constructed samples simulating the
      heterogeneity of natural samples. In effect, our data show that the results
      obtained in the nested PCR can be altered by the amount of template used in the
      reaction and, therefore, some heterogeneous samples might be classified
      mistakenly as homogeneous, simple mutant or simple wild type. These observations
      may explain, at least in part, contradictory results found in the literature. Our
      data also suggest the need for a more cautious approach to interpretation of the
      results of nested PCR assays with mutation-specific primers and their
      implications in the definition of resistance to the pyrimethamine-sulfadoxine
      combination.

PMID- 11846522
TI  - Measure of molecular diversity within the Trypanosoma brucei subspecies
      Trypanosoma brucei brucei and Trypanosoma brucei gambiense as revealed by
      genotypic characterization.
AB  - We have evaluated whether sequence polymorphisms in the rRNA intergenic spacer
      region can be used to study the relatedness of two subspecies of Trypanosoma
      brucei. Thirteen T. brucei isolates made up of 6 T. b. brucei and 7 T. b.
      gambiense were analyzed using restriction fragment length polymorphism (RFLP). By
      PCR-based restriction mapping of the ITS1-5.8S-ITS2 ribosomal repeat unit, we
      found a fingerprint pattern that separately identifies each of the two subspecies
      analyzed, with unique restriction fragments observed in all but 1 of the T. b.
      gambiense "human" isolates. Interestingly, the restriction profile for a virulent
      group 2 T. b. gambiense human isolate revealed an unusual RFLP pattern different
      from the profile of other human isolates. Sequencing data from four
      representatives of each of the two subspecies indicated that the intergenic
      spacer region had a conserved ITS-1 and a variable 5.8S with unique
      transversions, insertions, or deletions. The ITS-2 regions contained a single
      repeated element at similar positions in all isolates examined, but not in 2 of
      the human isolates. A unique 4-bp [C(3)A] sequence was found within the 5.8S
      region of human T. b. gambiense isolates. Phylogenetic analysis of the data
      suggests that their common ancestor was a nonhuman animal pathogen and that human
      pathogenicity might have evolved secondarily. Our data show that cryptic species
      within the T. brucei group can be distinguished by differences in the PCR-RFLP
      profile of the rDNA repeat.

PMID- 11846523
TI  - Entamoeba histolytica: transferrin binding proteins.
AB  - Entamoeba histolytica trophozoites depend on iron for their growth; thus, they
      must use some host iron-containing molecules to fulfill this requirement. In this
      work we report that amoebas are able to utilize human holo-Tf as iron source and
      to recognize it through transferrin binding proteins. By use of an anti-human
      transferrin antiserum in an immunoblotting assay, two main polypeptides with
      apparent molecular masses of 70 and 140 kDa were found in total extract of
      trophozoites cultured in vitro. However, when a monoclonal anti-human transferrin
      receptor antibody was used, only one band with molecular mass of 140 kDa was
      observed. Both the human transferrin and the monoclonal antibody recognized a
      protein on the amoebic surface, demonstrated by confocal microscopy. Furthermore,
      the complex transferrin-transferrin binding protein was internalized by an
      endocytic process and probably dissociated inside the cell. This mechanism could
      be one manner in which E. histolytica acquires iron from the human host
      transferrin.

PMID- 11846524
TI  - Gene amplification in amphotericin B-resistant Leishmania tarentolae.
AB  - Two Leishmania tarentolae cells were selected step by step for resistance to the
      polyene antibiotic amphotericin B, a second-line drug against the parasite
      Leishmania. One of the mutants was cross-resistant to ketoconazole. DNA
      amplification was observed in both mutants. The amplicons were extrachromosomal
      circles and were derived from different chromosomes. In one mutant the circle was
      unusually stable as it remained within the cell despite numerous passages in the
      absence of the drug. A circumstantial link between the copy number of amplicons
      and the resistance levels was established. Gene transfection experiments
      indicated that the link between the locus amplified and the resistance levels was
      not straightforward and possibly several mutations act together to lead to
      amphotericin B resistance.

PMID- 11846525
TI  - Histopathology of Trypanosoma (Trypanozoon) evansi infection in bandicoot rat. I.
      visceral organs.
AB  - Experimental infection of Trypanosoma (Trypanozoon) evansi in Bandicota
      bengalensis produces an acute disease course leading to untimely death of the
      bandicoot rat. The sequential alteration of liver, spleen, lung, kidney, and
      heart was studied on the 5th, 8th, 12th, and 14th days postinoculation. The rats
      showed inflammatory, degenerative, and necrotic changes in these organs. In
      liver, pseudolobule formation, necrosis and hemorrhage within the sinusoids, and
      fatty degeneration of hepatic cells were the predominant histopathological
      changes. The changes were destructive and irreversible. In spleen giant cells
      aggregation and granulomatous lesion, i.e., accumulation of histiocytes, were the
      protective changes, whereas tissue and cell damage indicated irreversible
      degeneration. The gradual development of intrabronchus inflammation, aggregation
      of inflammatory cells around the alveoli, congestion of bronchioles, septal
      edema, atrophy of alveolar walls, migration of macrophages, and emphysema were
      the histopathological changes noticed in the lungs of the infected rats. The
      affected kidney showed infiltration of lymphocytes, hemorrhage in the
      interlobular space, and glomerulitis as the irreversible and destructive changes
      in the rats. There was degeneration of myocardium in the hearts of the rats. The
      histopathological changes in these organs are compared with those studied in
      surra, human sleeping sickness disease, and African trypanosomiasis. Possible
      mechanisms for these histological changes in the visceral organs are discussed.

PMID- 11846526
TI  - Trypanosoma cruzi: characterization of reinfection and search for tissue tropism
      in hamsters (Mesocricetus auratus).
AB  - Tissue tropism, the role of reinfection in the development of Chagas' disease,
      and the selection of subpopulations of Trypanosoma cruzi were evaluated in
      hamsters inoculated with the VIC strain of T. cruzi. Adult allogeneic male
      hamsters were inoculated once or reinoculated by the intraperitoneal route up to
      four times with 2000 blood trypomastigotes. Animals were studied by blood
      culture, histopathology, immunohistochemistry, and molecular techniques (PCR and
      low-stringency single specific primer-PCR). Homogeneity of the T. cruzi
      population observed in different tissues suggests that selective tropism of the
      VIC strain extends only to various muscle tissues in hamsters and that
      reinfection is not a factor in the development of the inflammatory processes,
      although it may aggravate it, possibly due to an increase in tissue parasitism,
      which might induce autoimmune mechanisms. Reinfection did not induce selection of
      subpopulations in the tissue or in the blood.

PMID- 11846527
TI  - Babesia bovis: culture of laboratory-adapted parasite lines and clinical isolates
      in a chemically defined medium.
AB  - Babesiosis caused by Babesia spp. is a disease of both veterinary and human
      importance. Here, we describe a method to continuously culture laboratory lines
      and field isolates of Babesia bovis in vitro in a chemically defined medium using
      (ALBU)MAX II as an alternative to bovine serum. Further, we have successfully
      cultured parasite isolates directly from cattle that failed to grow in
      traditional serum-containing medium. Variation of atmospheric gas composition and
      culture volumes to determine optimal growth conditions revealed that a 600-microl
      culture in an atmosphere comprising 5% O(2), 5% CO(2), and 90% N(2) achieved a
      significantly higher percentage of parasitized red blood cells than any other
      combination tested. The process could be scaled up to reliably produce large
      volumes of parasites. Supplementation of the culture medium with hypoxanthine
      further improved parasite growth. B. bovis cultured in this way could be the
      basis of an alternative, safer vaccine and a reliable source of parasites and
      exoantigens for parasitological research.

PMID- 11846528
TI  - Plasmodium vivax: polymerase chain reaction amplification artifacts limit the
      suitability of pvgam1 as a genetic marker.

PMID- 11846530
TI  - A fossil stapes from Sterkfontein, South Africa, and the hearing capabilities of
      early hominids.

PMID- 11846532
TI  - Additional human remains from Blombos Cave, South Africa: (1999-2000
      excavations).
AB  - The uppermost Middle Stone Age (MSA) layers at Blombos Cave contain high
      densities of Still Bay bifacial points. Information from other regional sites
      places the Still Bay prior to the Howiesons Poort industry, which has been dated
      at 65-70 ka. The Blombos Cave MSA strata have yielded nine human teeth or dental
      fragments. Four that were recovered during the 1997-1998 excavations have been
      published elsewhere. The remaining five were discovered during the 1999-2000
      field seasons; these are described here. Three of the new specimens are deciduous
      teeth, and two are permanent premolar and molar crown fragments. The entire
      dental sample probably represents at least five and as many as seven individuals.
      The deciduous teeth from the upper MSA levels are likely to have been exfoliated
      in the cave. One deciduous tooth and the permanent tooth fragments from the lower
      MSA levels probably represent three individuals who died in or near the cave. The
      Blombos Cave premolars preserve horizontal circum-cervical striae suggestive of
      palliative tooth pick use. Approximately half of the permanent and deciduous
      crown diameters exceed those of recent Africans; for the remainder, the fossil
      values fall among modern African sample means. The Blombos Cave tooth crowns tend
      to be smaller than the majority of penecontemporaneous Neandertal teeth. The
      morphology of the Blombos Cave di is comparable to MSA homologues from the
      nearby, and presumably somewhat younger site of Die Kelders Cave 1.

PMID- 11846531
TI  - Skeletal and dental morphology of African papionins: unmasking a cryptic clade.
AB  - One of the more perplexing problems in primate systematics concerns the phyletic
      relationships of the large African monkeys--Mandrillus (including drills), Papio,
      Lophocebus and Cercocebus. For over twenty years, there has been molecular
      evidence that mangabeys are an unnatural group and that the terrestrial forms-
      Cercocebus--are the sister taxon of Mandrillus, while the arboreal forms-
      Lophocebus--are more closely allied with Papio. Nevertheless, most systematists
      have been reluctant to accept this scheme due to the lack of morphological
      evidence. In this paper, we undertake a detailed analysis of the scapula,
      humerus, radius, ulna, pelvis, femur and dentition of papionin primates. We
      identify a host of features shared by Cercocebus and Mandrillus to the exclusion
      of Lophocebus and Papio. The polarity of characters is established by examining
      an outgroup comprised of several species of Macaca. The features shared by
      Cercocebus and Mandrillus are functionally related to specific feeding and
      locomotor behaviors that include aggressive manual foraging, the processing of
      hard-object foods and the climbing of vertical trunks. We hypothesize that the
      ability to subsist on hard seeds and nuts gleaned from the forest floor is a key
      adaptation for the Cercocebus-Mandrillus clade.

PMID- 11846534
TI  - Operating theatre ventilation standards and the risk of postoperative infection.
AB  - Some form of specialized ventilation has been a feature of operating theatres for
      over 60 years, and ultraclean ventilation has been shown to reduce postoperative
      infection after prosthetic joint surgery. However, controversy remains over the
      contribution of plenum (conventional) ventilation to the prevention of infection
      after surgery in which there is no prosthetic implant. A previous survey in Great
      Britain and Ireland indicated the continued use of non-ventilated theatres for
      minor surgery. Laparoscopic and other forms of minimally invasive surgery (MIS)
      have become more common in the last decade, and offer the advantages of reduced
      morbidity and shorter hospital stay. However, it is not clear whether such
      surgery requires the same standard of ventilation facilities as open surgery and,
      in particular, whether all MIS procedures should be performed in a plenum
      ventilated theatre. Furthermore, there are many diagnostic and therapeutic
      procedures currently performed in cardiac and radiology departments where only
      natural ventilation is available. The Hospital Infection Society (HIS) Working
      Party on Infection Control and Operating Theatres is attempting to assess the
      ventilation facilities currently utilized for a wide variety of MIS procedures.
      This review should form the basis of future HIS guidance on minimum standards in
      this area.

PMID- 11846533
TI  - The costal skeleton of Shanidar 3 and a reappraisal of Neandertal thoracic
      morphology.
AB  - For over a century, Neandertal rib remains have engendered frequent discussions
      of "barrel-shaped" thoraces, largely in the absence of systematic comparison and
      hard data. We present here a description of the relatively complete ribcage of
      the Near Eastern Shanidar 3 Neandertal. We also furnish metric and non-metric
      comparisons of the Shanidar 3 ribs with other Near Eastern and European
      Neandertals, the Nariokotome (Homo erectus/ergaster) specimen, Levantine
      archaic/early modern humans, early and later European modern humans, and a sample
      of recent Euroamerican males. It is clear from these comparisons that Neandertals
      share with modern humans the fundamentally human thoracic "bauplan" that first
      evolved in the early Pleistocene. Yet it is also apparent that the ribcage of
      Neandertals differ in several anatomical details from those of fully modern
      humans. Rib curvature, posterior angle, mid-shaft cross-sectional size and shape,
      and muscle scarring varies considerably among Neandertals and across all samples
      when considered in isolated ribs. However, normalized metric and discrete
      patterning across the greater thorax clearly distinguishes Neandertals from our
      comparative samples. This is most marked in the inferior thorax where Neandertals
      (and probably earlier Homo) exhibit larger, more rounded and rugose ribs, and a
      greater costal area (thoracic volume). Greater lower rib cross-sectional
      robusticity and muscle scarring indicates relatively elevated ventilatory levels.
      Greater thoracic volume in Neandertals probably reflects greater body mass
      compared with modern humans since lung volume scales isometrically to body mass
      among mammals. Neandertal and modern human pulmonary capacity, normalized for
      body mass differences, was therefore roughly equivalent in the context of
      detailed differences in thoracic shape. To the extent that cold-climate
      adaptation is involved, Near Eastern Neandertals appear less "hyper-polar" in
      thoracic shape than their European counterparts as is also true for several other
      body proportion measures that are clinally distributed across the known
      Neandertal range.

PMID- 11846535
TI  - Nosocomial cardiac infections.
AB  - The most important nosocomial cardiac infections include nosocomial infective
      endocarditis on native and prosthetic valves, and nosocomial infections related
      to transvenous permanent pacemakers, implantable cardioverter-defibrillators and
      left ventricular assist devices. Although representing rare complications, they
      are of great importance because they are associated with high morbidity and
      mortality. Most of them are encountered in older-age groups, related to
      nosocomial invasive procedures performed within the preceding four to eight weeks
      of hospital admission. Nosocomial bacteraemia associated with infected central
      intravascular devices, genitourinary or gastrointestinal tract surgery and
      instrumentation, breaks in sterile surgical techniques at the implantation of
      prosthetic valves and cardiac devices as well as wound and skin infections,
      represent the most important risk factors. Staphylococcus aureus in native valve
      endocarditis and S. epidermidis in the presence of foreign bodies are the main
      implicated pathogens. However, because of the steeply increasing incidence of
      candidaemia in tertiary hospitals, nosocomial cardiac infections caused by
      Candida spp. have also been steadily increasing over the last decades. Diagnosis
      of nosocomial cardiac infections, particularly in the presence of foreign bodies,
      is often difficult because of the severity of patients' co-morbid illnesses and
      the co-existence of several risk factors. Diagnosis should be based on positive
      blood cultures and transoesophageal echocardiographic findings in febrile high
      risk patients. Therapy necessitates a combination of antibiotics and surgical
      removal of foreign bodies. Prophylaxis should mainly target the prevention and/or
      appropriate treatment of bacteraemias secondary to infected intravascular
      devices, as well as application of prophylaxis guidelines whenever invasive
      hospital-based procedures are performed in high-risk individuals.

PMID- 11846536
TI  - Infection control in Britain.

PMID- 11846538
TI  - Nosocomial infections and misuse of antibiotics in a provincial community
      hospital, Saudi Arabia.
AB  - The incidence of nosocomial infection and prevalence of antibiotic misuse were
      studied in a 174-bed community hospital in Saudi Arabia over a six-month period.
      Of 2445 patients admitted, 8.5% developed nosocomial infection, the rates were
      highest for nursery (35.8%), intensive care (19.8%), gynaecological (16.2%) and
      surgical (11.7%) patients. Urinary tract (31.3%), wound (27.1%) and blood (14.9%)
      infections accounted for more than 70% of the infections. Staphylococcus aureus
      (23%) and Pseudomonas aeruginosa (11%), caused more than 90% of the infections.
      The majority of the bacterial pathogens (79%) were multi-drug resistant. Over 80%
      of patients were administered prophylactic and/or therapeutic antibiotics, with
      53% receiving multiple antibiotics; 72% of the antibiotics were judged to be
      misused. Both prophylaxis and treatment were mostly misguided and clinically
      unwarranted. Host- and hospital-associated infection risk factors were
      identified. The minimum government cost estimates for the nosocomial infections
      and misused antibiotics were US $273 180 and $565 603, respectively. The findings
      emphasize the need for effective measures to reduce both the high infection rates
      and widespread antibiotic misusage in the hospital. Such measures should include
      institution of an effective infection control committee and a hospital antibiotic
      policy.

PMID- 11846537
TI  - Carbapenem-resistant Acinetobacter and role of curtains in an outbreak in
      intensive care units.
AB  - Multiple-antibiotic-resistant Acinetobacter baumanii, including meropenem
      resistance, was first isolated from a patient in the general intensive care unit
      of a tertiary-referral university teaching hospital in Birmingham in December
      1998. Similar strains were subsequently isolated from 12 other patients,
      including those on another intensive care unit within the hospital. The outbreak
      followed an increase in the use of meropenem in both the units. Environmental
      screening revealed the presence of the multiple-resistant Acinetobacter species
      on fomite surfaces in the intensive care unit and bed linen. The major source
      appeared to be the curtains surrounding patients' beds. Typing by pulsed field
      gel electrophoresis demonstrated that the patients' isolates and those from the
      environment were indistinguishable. Rigorous infection control measures including
      increased frequency of cleaning of the environment with hypochlorite (1000 ppm)
      and twice-weekly changing of curtains were implemented, along with restriction of
      meropenem use in the units. Isolation of the multiple-resistant Acinetobacter
      spp. subsequently diminished and it was not detected over a follow-up period of
      18 months. To our knowledge, this is the first reported outbreak of carbapenem
      resistant Acinetobacter spp. from the UK. This outbreak also highlights
      environmental sources, particularly dry fabrics such as curtains, as an important
      reservoir for dissemination of acinetobacters.

PMID- 11846539
TI  - Prevalence of methicillin-resistant Staphylococcus aureus carriage at the time of
      admission in two acute geriatric wards.
AB  - Studies on methicillin-resistant Staphylococcus aureus (MRSA) in the elderly have
      been concerned with patients hospitalized in nursing homes or long-term care
      facilities. Our objective was to estimate the prevalence of MRSA at the time of
      admission in two acute geriatric wards with high endemic MRSA incidence in a
      French teaching hospital. A prospective screening of MRSA carriers was conducted
      by swabbing nares and wounds during five weeks for all patients on the day of
      admission. For each patient demographic, administrative, clinical and therapeutic
      data were recorded. Their associations with MRSA carriage were studied by
      logistic regression analysis. On the day of admission, 35 patients (14.6%) were
      MRSA carriers. Variables independently associated with carriage were
      hospitalization within the six last months (OR = 4.64; P < 0.001) and the
      existence of wounds or bedsores (OR = 2.864; P = 0.02). The high prevalence of
      MRSA carriage at the time of admission could explain in part the high incidence
      of MRSA in these wards. A systematic selective screening targeted on patients
      with high risk of carriage should be helpful to implement barrier precautions and
      reduce cross-transmission.

PMID- 11846540
TI  - The use of adult isolation facilities in a UK infectious diseases unit.
AB  - The emergence and re-emergence of communicable infections, especially those due
      to antibiotic resistant nosocomial pathogens, is likely to increase the burden on
      the limited isolation facilities of the UK. It was our perception, however, that
      isolation beds are not always used optimally; with patients requiring isolation
      sometimes being housed in open-bay beds, whilst other non-communicable patients
      are unnecessarily isolated. The main aim of this study was to test this
      hypothesis in a regional infectious diseases (ID) unit. A secondary aim was to
      provide useful data in the development of guidelines for the admission of
      patients to the new Dundee ID unit. One-third of patients (32% of all patients
      and 34% of total bed days) admitted to an isolation room in the current Dundee ID
      unit over a four-month period, were found to have low-risk or non-communicable
      conditions. In addition, 21 patients initially considered an infection risk, used
      102 bed days following resolution of their infection. Evidence for the presence
      of patients with 'alert' infections housed in the open-bay beds of other wards,
      whilst low-risk or non-communicable patients are unnecessarily exposed to
      isolation in the ID unit, is presented. The findings suggest suboptimal use of
      the current Tayside University Hospitals' isolation facilities. Given the
      likelihood of high demand for the isolation of patients in the new Dundee ID
      unit, it is vital that these facilities are used appropriately, thereby
      minimizing the risk of nosocomial infection transmission and the unnecessary
      isolation of low-risk patients.

PMID- 11846541
TI  - Survival of enterococci during hospital laundry processing.
AB  - Much remains to be elucidated about the epidemiology of nosocomial enterococcal
      infections. Enterococci are, however, known to be relatively thermotolerant, and
      several studies have shown that under laboratory conditions many strains are able
      to survive the time/temperature combinations of the UK Department of Health
      recommendations for the decontamination of used linen (HSG(95)18). We therefore
      wished to investigate the efficacy of decontamination of enterococci from
      hospital linen in working hospital laundries. The thermotolerance of 40 strains
      of Enterococcus faecalis and Enterococcus faecium was first determined. Reduction
      by a factor of greater than 10(5) was achieved in only two of 40 strains after 3
      min at 71 degrees C or 10 min at 65 degrees C, the time/temperature combinations
      specified by the Department of Health for the disinfection of used linen. During
      experimental challenge of 10 working hospital laundries, however, we demonstrated
      successful decontamination of laundry artificially contaminated with enterococci.
      This was shown to take place during the washing stage. Our study suggests that,
      despite the relative thermotolerance of enterococci, the time/temperature
      combinations specified in HSG(95)18 should be adequate for their decontamination
      in hospital laundries.

PMID- 11846542
TI  - Bactericidal activities of disinfectants against vancomycin-resistant
      enterococci.
AB  - The bactericidal activities of 35 commercially available disinfectants against
      vancomycin-resistant enterococci (VRE) and vancomycin-sensitive enterococci (VSE)
      were investigated under both clean and dirty (albumin added) conditions using a
      microtitration plate method. No differences in bactericidal time were observed
      with any of the test disinfectants when comparing activity against VRE or VSE.
      Isopropyl alcohol (70 v/v%), alcohol-containing preparations such as Welpas,
      Wellup and Maskin W . ethanol solution, 0.2% of cation surfactant disinfectants
      such as Osvan solution 'daigo', Germitol 'Maruishi' 10% and Hyamine solution, and
      0.5% of amphoteric compound disinfectants such as TEGO-51, Hygieel and Hypal
      No.3, were the most effective compounds when compared with other disinfectants.
      These results suggest that the use of a disinfectant with activity against VRE
      may be one appropriate method for preventing infections caused by this micro
      organism.

PMID- 11846544
TI  - Eight-year surveillance of environmental fungal contamination in hospital
      operating rooms and haematological units.
AB  - An eight-year fungal environmental surveillance was carried out in 15 operating
      theatres and two haematological units. Sampling was performed twice a year in
      each room, using contact plates for plane surfaces and sterile swabs for grids.
      From 1992 to 1999, individual rooms in the 17 units were sampled on 1094
      occasions and 3822 samples were collected. The percentage of rooms without fungus
      increased regularly between 1992 and 1999 (41.1% and 74.8%, respectively). The
      units were classified according to the fungal contamination during the eight
      years: the operating theatres which required the highest protection
      (cardiological, thoracic, vascular, hand, orthopaedic and neurosurgery) and the
      adult haematological unit showed least contamination (71.8% rooms were negative).
      The most frequent species isolated were Penicillium spp. (28.4%), Cladosporium
      spp. (15.6%) and Aspergillus spp. (7.6%). Aspergillus fumigatus was rarely
      isolated (3.7%), and was mainly isolated at the beginning of the study. This
      study demonstrates that environmental control programmes are effective in
      reducing environmental mould contamination and could be useful in establishing
      exposure guidelines, especially by defining an acceptable level of
      biocontamination in zones at risk.

PMID- 11846543
TI  - The prevalence of faecal carriage of ampicillin-resistant and high-level
      gentamicin-resistant enterococci among inpatients at 10 major Norwegian
      hospitals.
AB  - From March to October 1999, 854 patients hospitalized at 10 major Norwegian
      hospitals were screened for rectal carriage of ampicillin-resistant enterococci
      (ARE) and high-level gentamicin-resistant enterococci (HLGRE). A total of 59 ARE
      carriers (prevalence 6.9%, range 0-22% among hospitals) and 28 HLGRE carriers
      (prevalence 3.3%, range 1-11%) were detected. All ARE or HLGRE strains were
      susceptible to vancomycin, whereas 77% of the ARE isolates were resistant to
      ciprofloxacin. All the ARE strains were identified as Enterococcus faecium, and
      48% of these were genomically closely related as shown by PFGE. Specific point
      mutations in the pbp5 gene were associated with reduced susceptibility to
      ampicillin. The adjusted risk of becoming a carrier of ARE was related to the use
      of glycopeptides [odds ratio (OR) = 4.8], the use of any antimicrobial agent (OR
      = 3.1) and more than one hospital admission during the last six months (OR =
      2.0). Twenty-five of 28 HLGRE isolates were Enterococcus faecalis. The aacA/aphD
      genes were detected in 26 (93%) and the aphA3 in 19 (68%) of the HLGRE isolates.
      Sixty-four percent of the HLGRE isolates belonged to two PFGE clusters.
      Consumption of antimicrobial agents was also a significant risk factor for HLGRE
      colonization (OR = 5.4), while prescription of penicillins was associated with
      reduced risk (OR = 0.28).

PMID- 11846546
TI  - Impact on compliance of the introduction of rub-in hand disinfection: non
      significant improvement or interaction between units?

PMID- 11846548
TI  - Regulated assembly of transcription factors and control of transcription
      initiation.
AB  - Proteins that function in regulation of transcription initiation are typically
      homo or hetero-oligomeric. Results of recent biophysical studies of transcription
      regulators indicate that the assembly of these proteins is often subject to
      regulation. This regulation of assembly dictates the frequency of transcription
      initiation via its influence on the affinity of a transcription regulator for DNA
      and its affect on target site selection. Factors that modulate transcription
      factor assembly include binding of small molecules, post-translational
      modification, DNA binding and interactions with other proteins. Here, the results
      of recent structural and/or thermodynamic studies of a number of transcription
      regulators that are subject to regulated assembly are reviewed. The accumulated
      data indicate that this phenomenon is ubiquitous and that mechanisms utilized in
      eukaryotes and prokaryotes share common features.

PMID- 11846549
TI  - The structure of intramolecular triplex DNA: atomic force microscopy study.
AB  - We applied atomic force microscopy (AFM) for direct imaging of intramolecular
      triplexes (H-DNA) formed by mirror-repeated purine-pyrimidine repeats and
      stabilized by negative DNA supercoiling. H-DNA appears in atomic force microscopy
      images as a clear protrusion with a different thickness than DNA duplex.
      Consistent with the existing models, H-DNA formation results in a kink in the
      double helix path. The kink forms an acute angle so that the flanking DNA regions
      are brought in close proximity. The mobility of flanking DNA arms is limited
      compared with that for cruciforms and three-way junctions. Structural properties
      of H-DNA may be important for promoter-enhancer interactions and other DNA
      transactions.

PMID- 11846550
TI  - NMR studies of the interactions of SpoIIAA with its partner proteins that
      regulate sporulation in Bacillus subtilis.
AB  - SpoIIAA is a key component in the network of interactions that regulate the first
      sporulation-specific transcription factor, sigma(F), in Bacillus subtilis. In its
      unphosphorylated form SpoIIAA is either phosphorylated by or forms a non-covalent
      complex with SpoIIAB, whereas in its phosphorylated form it is dephosphorylated
      by SpoIIE. In this work we present NMR studies of the SpoIIAA(2).SpoIIAB complex
      and of mutant proteins that are deficient in their ability to interact with
      SpoIIAB or SpoIIE. The NMR studies of the SpoIIAA(2).SpoIIAB complex allowed us
      to define a contiguous patch that is perturbed upon complex formation. By
      examining the chemical shift perturbations in the mutant proteins we have
      identified more specific areas that contain residues critical for the SpoIIAB and
      SpoIIE interactions.

PMID- 11846551
TI  - Homology between O-linked GlcNAc transferases and proteins of the glycogen
      phosphorylase superfamily.
AB  - The O-linked GlcNAc transferases (OGTs) are a recently characterized group of
      largely eukaryotic enzymes that add a single beta-N-acetylglucosamine moiety to
      specific serine or threonine hydroxyls. In humans, this process may be part of a
      sugar regulation mechanism or cellular signaling pathway that is involved in many
      important diseases, such as diabetes, cancer, and neurodegeneration. However, no
      structural information about the human OGT exists, except for the identification
      of tetratricopeptide repeats (TPR) at the N terminus. The locations of substrate
      binding sites are unknown and the structural basis for this enzyme's function is
      not clear. Here, remote homology is reported between the OGTs and a large group
      of diverse sugar processing enzymes, including proteins with known structure such
      as glycogen phosphorylase, UDP-GlcNAc 2-epimerase, and the glycosyl transferase
      MurG. This relationship, in conjunction with amino acid similarity spanning the
      entire length of the sequence, implies that the fold of the human OGT consists of
      two Rossmann-like domains C-terminal to the TPR region. A conserved motif in the
      second Rossmann domain points to the UDP-GlcNAc donor binding site. This
      conclusion is supported by a combination of statistically significant PSI-BLAST
      hits, consensus secondary structure predictions, and a fold recognition hit to
      MurG. Additionally, iterative PSI-BLAST database searches reveal that proteins
      homologous to the OGTs form a large and diverse superfamily that is termed GPGTF
      (glycogen phosphorylase/glycosyl transferase). Up to one-third of the 51
      functional families in the CAZY database, a glycosyl transferase classification
      scheme based on catalytic residue and sequence homology considerations, can be
      unified through this common predicted fold. GPGTF homologs constitute a
      substantial fraction of known proteins: 0.4% of all non-redundant sequences and
      about 1% of proteins in the Escherichia coli genome are found to belong to the
      GPGTF superfamily.

PMID- 11846552
TI  - Transcription attenuation associated with bacterial repetitive extragenic BIME
      elements.
AB  - Transcription attenuation comprises several processes that affect transcript
      elongation and transcription termination, and has an important role in regulating
      gene expression. In most cases, transcription attenuation is used as a regulatory
      mechanism that allows the cell to adjust protein synthesis levels in response to
      a specific signal. Here, by using a tRNA gene as a transcriptional reporter, we
      characterize a new type of transcription attenuation mechanism in Escherichia
      coli that involves bacterial interspersed mosaic elements (BIMEs), the main
      family of repetitive extragenic elements. The transcription termination factor
      Rho is required for attenuation in association with BIMEs, thus revealing a new
      role for Rho as a BIMEs-dependent global regulator of gene expression. By
      mutational analyses, we identified nucleotide determinants of BIMEs that are
      required for attenuation and showed that this process relies on a sequence
      specific mechanism. Our data are consistent with a model in which BIMEs provoke a
      pause in RNA polymerase movement and Rho acts ultimately to terminate
      transcription. BIME-dependent transcription attenuation may be used as a means to
      differentially regulate expression of adjacent genes belonging to a single
      operon. BIMEs are dispersed in more than 250 operons such that attenuation can
      simultaneously affect expression of a large number of genes encoding unrelated
      proteins. This attenuation phenomenon, together with the known ability of BIMEs
      to stabilize upstream mRNA, reveals how dispersion of these abundant repetitive
      elements may affect gene regulation at the genome level.

PMID- 11846553
TI  - Role of the ATP-binding site of SopA protein in partition of the F plasmid.
AB  - SopA belongs to a large family of bacterial partition protein ATPases. It helps
      stabilize the F plasmid by acting as the primary repressor of transcription of
      the sopAB operon, preventing the destabilizing effects of Sop protein excess. It
      is also thought to act directly in the F partition mechanism. We have examined
      the role of SopA in partition and repression by observing the consequences of
      replacing an invariant ATP-binding site lysine, K120, by glutamine or arginine.
      Circular dichroism studies of the purified mutant proteins revealed no major
      differences from wild-type, but in the presence of ADP or ATP each protein showed
      a characteristic spectrum which suggested a distinct conformational change. The
      K120Q mutant retained most of the wild-type ATPase activity while the K120R
      mutant lost it. In neither case was the residual activity stimulated by SopB, as
      occurs for wild-type SopA. The strength of sop promoter repression by the mutant
      SopA proteins alone was comparable to that resulting from SopB-enhancement of
      wild-type SopA, but SopB enhanced repression by the mutant SopA proteins either
      slightly (K120R) or not at all (K120Q). Mini-Fs in which the sop operon was
      controlled by a constitutive promoter were destabilized by the mutations,
      demonstrating the need for SopA and its ATP-binding site in the partition
      process. The K120R mini-F was lost at the same rate as a mini-F lacking the sopC
      centromere, the K120Q mutant was lost faster. SopAK120R at high levels was more
      effective than SopA(+) in disrupting the partition complex, whereas SopAK120Q did
      not disrupt it at all. These results suggest that one function of SopA in the
      partition mechanism is to break the paired plasmid structure to allow F molecules
      to segregate to daughter cells.

PMID- 11846554
TI  - The N-terminal ATPase site in the large terminase protein gp17 is critically
      required for DNA packaging in bacteriophage T4.
AB  - Double-stranded DNA packaging in bacteriophages is apparently driven by the most
      powerful molecular motor ever measured. Although it is widely accepted that a
      translocating ATPase powers the DNA packaging machine, the identity of the ATPase
      that generates this driving force is unknown. Evidence suggests that the large
      terminase protein gp17, which possesses two consensus ATP binding motifs and an
      ATPase activity, is a strong candidate for the translocating ATPase in
      bacteriophage T4. This hypothesis was tested by a PCR-directed combinatorial
      mutagenesis approach in which mutant libraries consisting of all possible codon
      combinations were constructed at the signature residues of the ATP binding
      motifs. The impact on gp17 function of each randomly selected mutant was
      evaluated by phenotypic analysis following recombinational transfer into the
      viral genome. The precise mutation giving rise to a particular phenotype was
      determined by DNA sequencing. The data showed that the N-terminal ATP binding
      site I (SRQLGKT(161-167)), but not the ATP binding site II (TAAVEGKS(299-306)),
      is critical for gp17 function. Even conservative substitutions such as G165A,
      K166R, and T167A were not tolerated at the GKT signature residues, which are
      predicted to interact with the ATP substrate. Biochemical analyses of the mutants
      showed a complete loss of in vitro DNA packaging activity but not the terminase
      (DNA-cutting) activity. The purified K166G mutant showed a loss of gp17-ATPase
      activity. The data, for the first time, implicated a specific ATPase center in
      the viral dsDNA packaging.

PMID- 11846555
TI  - Interaction of the Bacillus stearothermophilus ribosomal protein S15 with its 5'
      translational operator mRNA.
AB  - The Bacillus stearothermophilus ribosomal protein S15 (BS15) binds both a three
      helix junction in the central domain of 16 S ribosomal RNA and its cognate mRNA.
      Native gel mobility-shift assays show that BS15 interacts specifically and with
      high affinity to the 5'-untranslated region (5'-UTR) of this cognate mRNA with an
      apparent dissociation constant of 3(+/-0.3) nM. In order to localize the
      structural elements that are essential for BS15 recognition, a series of deletion
      mutants of the full cognate mRNA were prepared and tested in the same gel-shift
      assay. The minimal binding site for BS15 is a 50 nucleotide RNA showing a close
      secondary structure resemblance to the BS15 binding region from 16 S rRNA. There
      are two major structural motifs that must be maintained for high-affinity
      binding. The first being a purine-rich three-helix junction, and the second being
      an internal loop. The sequence identity of the internal loops differs greatly
      between the BS15 mRNA and rRNA sites, and this difference is correlated to
      discrimination between wild-type BS15 and a BS15(H45R) mutant. The association
      and dissociation kinetics measured for the 5'-UTR-BS15 interaction are quite
      slow, but are typical for a ribosomal protein-RNA interaction. The BS15 mRNA and
      16 S rRNA binding sites share a common secondary structure yet have little
      sequence identity. The mRNA and rRNA may in fact present similar if not identical
      structural elements that confer BS15 recognition.

PMID- 11846556
TI  - An FTIR and CD study of the structural effects of G-tract length and sequence
      context on DNA conformation in solution.
AB  - Fourier transform infrared (FTIR) and CD spectroscopy have been used to
      investigate the structural effects of G-tract length and flanking sequence on the
      conformation of DNA G-tracts in aqueous solution. Particularly, a possible
      predisposition for A-form features has been probed, since this may be important
      for protein-DNA interactions. Five different G-tract-containing DNA duplexes have
      been studied: d[CATGGCCATG](2), d[CATGGGCCCATG](2), d[CATGGGGCCCCATG](2,)
      d[AGGGGCCCCT](2), and d[TGGGGCCCCA](2). In addition, a DNA duplex lacking a G
      tract center was probed (d[CATATGCATATG](2)). The CD and FTIR results show that
      the G-tract-containing sequences are all in a dominating B-DNA conformation in
      solution. However, certain spectral variations reflect structural effects of
      sequence context and G-tract length. CD spectra and FTIR results in the 1800-1500
      cm(-1) region show that the base-stacking pattern is greatly affected by the
      sequence context. The FTIR backbone 1250-1000 cm(-1) region shows the
      antisymmetric non-bridging phosphate vibration around 1225 cm(-1) in all
      sequences, demonstrating the overall B-conformation of the backbone. The FTIR
      sugar 900-800 cm(-1) region shows variable contributions of two bands around 865
      cm(-1) and 840 cm(-1), reflecting the N and S-type of sugar pucker. The relative
      intensities of the 865 cm(-1) and 840 cm(-1) bands have been proposed in the
      literature to quantitatively yield the contribution of N and S-type of sugar
      pucker, respectively. This correlation is supported by the present study.
      Furthermore, the contributions of N-type sugar in the DNA sequences studied
      indicate structural propensities that agree with trends in reported crystal
      structures of the same sequences: (1) d[CATGGCCATG](2), for which FTIR shows the
      lowest contribution of N-type sugar puckering in solution, crystallizes in a B
      like conformation; (2) d[AGGGGCCCCT](2), with the highest degree of N-type sugar
      puckering of all the sequences studied, crystallizes in an A-like conformation;
      (3) d[CATGGGCCCATG](2), with an N-type contribution intermediate between that of
      d[CATGGCCATG](2) and d[AGGGGCCCCT](2), crystallizes in an A/B intermediate
      conformation.

PMID- 11846557
TI  - Importance of the conserved CA dinucleotide at Mu termini.
AB  - The dinucleotide CA found at the termini of transposable phage Mu also occurs at
      the termini of a large class of transposable elements, including HIV, all
      retroviruses and many retrotransposons. In order to understand the importance of
      this sequence conservation, the activity of all 16 dinucleotide permutations of
      the termini was first examined using a sensitive plasmid-based in vivo
      transposition assay. The reactivity of these substrates varied over several
      orders of magnitude in vivo, with substitutions at the A position being more
      severely impaired than those at the C position. The same general hierarchy of
      reactivity was observed in vitro using mutant oligonucleotide substrates. These
      experiments revealed that CA was not important for the chemistry of strand
      transfer, and that the block in the activity of the mutant substrates was at the
      stage of assembly of a stable transpososome. Given that DNA at the Mu-host
      junctions is melted/distorted concomitantly with transpososome assembly, we
      consider the hypothesis that the CA dinucleotide has been selected at transposon
      termini primarily for its significant conformational mobility.

PMID- 11846558
TI  - Single amino acid substitutions in conserved extracellular domains of E-cadherin
      differ in their functional consequences.
AB  - The calcium-dependent homophilic cell adhesion molecule E-cadherin typically
      connects epithelial cells. The extracellular portion of the mature transmembrane
      protein consists of five homologous domains. The four sequences linking these
      domains contain the structural amino acid motif DXXD that is thought to be
      involved in direct calcium binding. In gastric cancer patients mutations
      affecting this motif between the second and third domain are frequently seen. In
      order to determine the functional significance of similar sequence alterations
      with regard to their location, we analyzed single amino acid substitutions
      changing the DXXD motif to DXXA in each linker region according to a mutation
      found in gastric cancer (D370A). The cDNA sequences coding for DQND, DVLD and
      DVND were changed (D257A, D479A, D590A, respectively) and stably expressed in E
      cadherin negative MDA-MB-435S mammary carcinoma cells. We found that the D257A
      and D370A mutations result in abnormal protein localization, changes in the actin
      cytoskeleton, markedly reduced homophilic cell adhesion, and altered cell
      morphology. Unexpectedly, the tumor-associated D370A mutation but not the D257A
      mutation induced increased cell motility. The D479A mutation only had slight
      functional consequences whereas cells expressing the D590A mutant did not differ
      from cells expressing the wild-type molecule. Although the putative calcium
      binding motif DXXD is located at repetitive positions in the extracellular
      portion of E-cadherin, our results indicate that it has different functions
      depending on the location. Remarkably, tumor cells select for mutations in the
      most critical domains resulting both in loss of function (decreased cell
      adhesion) and in gain of function (increased cell motility). Since multiple DXXD
      motifs are typically seen in other cadherins, our structure-function study is
      relevant for this gene family in general.

PMID- 11846559
TI  - Three-dimensional structure of an invertebrate rhodopsin and basis for ordered
      alignment in the photoreceptor membrane.
AB  - Invertebrate rhodopsins activate a G-protein signalling pathway in microvillar
      photoreceptors. In contrast to the transducin-cyclic GMP phosphodiesterase
      pathway found in vertebrate rods and cones, visual transduction in cephalopod
      (squid, octopus, cuttlefish) invertebrates is signalled via Gq and phospholipase
      C. Squid rhodopsin contains the conserved residues of the G-protein coupled
      receptor (GPCR) family, but has only 35% identity with mammalian rhodopsins.
      Unlike vertebrate rhodopsins, cephalopod rhodopsin is arranged in an ordered
      lattice in the photoreceptor membranes. This organization confers sensitivity to
      the plane of polarized light and also provides the optimal orientation of the
      linear retinal chromophores in the cylindrical microvillar membranes for light
      capture. Two-dimensional crystals of squid rhodopsin show a rectilinear
      arrangement that is likely to be related to the alignment of rhodopsins in
      vivo.Here, we present a three-dimensional structure of squid rhodopsin determined
      by cryo-electron microscopy of two-dimensional crystals. Docking the atomic
      structure of bovine rhodopsin into the squid density map shows that the helix
      packing and extracellular plug structure are conserved. In addition, there are
      two novel structural features revealed by our map. The linear lattice contact
      appears to be made by the transverse C-terminal helix lying on the cytoplasmic
      surface of the membrane. Also at the cytoplasmic surface, additional density may
      correspond to a helix 5-6 loop insertion found in most GPCRs relative to
      vertebrate rhodopsins. The similarity supports the conservation in structure of
      rhodopsins (and other G-protein-coupled receptors) from phylogenetically distant
      organisms. The map provides the first indication of the structural basis for
      rhodopsin alignment in the microvillar membrane.

PMID- 11846560
TI  - NTF2 monomer-dimer equilibrium.
AB  - Nuclear transport factor 2 (NTF2) mediates nuclear import of RanGDP, a central
      component of many nuclear trafficking pathways. NTF2 is a homodimer and each
      chain has independent binding sites for RanGDP and nuclear pore proteins
      (nucleoporins) that contain FxFG sequence repeats. We show here that the monomer
      dimer dissociation constant for NTF2 obtained by sedimentation equilibrium
      ultracentrifugation is in the micromolar range, indicating that a substantial
      proportion of cellular NTF2 may be monomeric. To investigate the functional
      significance of NTF2 dimerization, we engineered a series of point mutations at
      the dimerization interface and one of these (M118E) remained monomeric below
      concentrations of 150 microM. CD spectra and X-ray crystallography showed that
      M118E-NTF2 preserved the wild-type NTF2 fold, although its thermal stability was
      20 deg. C lower than that of the wild-type. M118E-NTF2 bound both RanGDP and FxFG
      nucleoporins less strongly, suggesting that dissociation of the NTF2 dimer could
      facilitate RanGDP release and thus nucleotide exchange after it had been
      transported into the nucleus. Moreover, colloidal gold coated with M118E-NTF2
      showed reduced binding to Xenopus oocyte nuclear pores. Overall, our results
      indicate that dimer formation is important for NTF2 function and give insight
      into the formation of heterodimers by mRNA export factors such as TAP1 and NXT1
      that contain NTF2-homology domains.

PMID- 11846561
TI  - Three-dimensional structure of renal Na,K-ATPase from cryo-electron microscopy of
      two-dimensional crystals.
AB  - The structure of Na, K-ATPase was determined by electron crystallography at 9.5 A
      from multiple small 2-D crystals induced in purified membranes isolated from the
      outer medulla of pig kidney. The density map shows a protomer stabilized in the
      E(2) conformation which extends approximately 65 A x 75 A x 150 A in the
      asymmetric unit of the P2 type unit cell. The alpha, beta, and gamma subunits
      were demonstrated in the membrane crystals with Western blotting and related to
      distinct domains in the density map. The alpha subunit corresponds to most of the
      density in the transmembrane region as well as the large hydrophilic headpiece on
      the cytoplasmic side of the membrane. The headpiece is divided into three
      separated domains, which are similar in overall shape to the domains of the
      calcium pump of the sarcoplasmic reticulum. One of these domains gives rise to a
      characteristic elongated projection onto the membrane plane while the putative
      nucleotide binding and phosphorylation domains form comparatively compact
      densities in the rest of the cytoplasmic part of the structure. Density on the
      extracellular face corresponds to the protein part of the beta subunit and is
      located as an extension of the transmembrane region perpendicular to the membrane
      plane. The structure of the lipid bilayer spanning part suggests the positions
      for the transmembrane helix from the beta subunit as well as the small gamma
      subunit present in this Na,K-ATPase. Two groups of ten helices from the catalytic
      alpha subunit corresponds to the remaining density in the transmembrane region.
      The present results demonstrate distinct similarities between the structure of
      the alpha subunit of Na,K-ATPase as determined here by cryo-electron microscopy
      and the reported X-ray structure of Ca-ATPase. However, conformational changes
      between the E(1) and E(2) forms are suggested by different relative positions of
      cytoplasmatic domains.

PMID- 11846562
TI  - Crystal structure of a ternary SAP-1/SRF/c-fos SRE DNA complex.
AB  - Combinatorial DNA binding by proteins for promoter-specific gene activation is a
      common mode of DNA regulation in eukaryotic organisms, and occurs at the promoter
      of the c-fos proto-oncogene. The c-fos promoter contains a serum response element
      (SRE) that mediates ternary complex formation with the Ets proteins SAP-1 or Elk
      1 and the MADS-box protein, serum response factor (SRF). Here, we report the
      crystal structure of a ternary SAP-1/SRF/c-fos SRE DNA complex containing the
      minimal DNA-binding domains of each protein. The structure of the complex reveals
      that the SAP-1 monomer and SRF dimer are bound on opposite faces of the DNA, and
      that the DNA recognition helix of SAP-1 makes direct contact with the DNA
      recognition helix of one of the two SRF subunits. These interactions facilitate
      an 82 degrees DNA bend around SRF and a modulation of protein-DNA contacts by
      each protein when compared to each of the binary DNA complexes. A comparison with
      a recently determined complex containing SRF, an idealized DNA site, and a SAP-1
      fragment containing a SRF-interacting B-box region, shows a similar overall
      architecture but also shows important differences. Specifically, the comparison
      suggests that the B-box region of the Ets protein does not significantly
      influence DNA recognition by either of the proteins, and that the sequence of the
      DNA target effects the way in which the two proteins cooperate for DNA
      recognition. These studies have implications for how DNA-bound SRF may modulate
      the DNA-binding properties of other Ets proteins such as Elk-1, and for how other
      Ets proteins may modulate the DNA-binding properties of other DNA-bound accessory
      factors to facilitate promoter-specific transcriptional responses.

PMID- 11846563
TI  - The crystal structure of a hyper-thermophilic carboxylesterase from the archaeon
      Archaeoglobus fulgidus.
AB  - The crystal structure of AFEST, a novel hyper-thermophilic carboxylesterase from
      the archaeon Archaeoglobus fulgidus, complexed with a sulphonyl derivative, has
      been determined and refined to 2.2 A resolution. This enzyme, which has recently
      been classified as a member of the hormone- sensitive-lipase (H) group of the
      esterase/lipase superfamily, presents a canonical alpha/beta hydrolase core,
      shielded on the C-terminal side by a cap region composed of five alpha-helices.
      It contains the catalytic triad Ser160, His285 and Asp255, whereby the
      nucleophile is covalently modified and the oxyanion hole formed by Gly88, Gly89
      and Ala161. A structural comparison of AFEST with its mesophilic and thermophilic
      homologues, Brefeldin A esterase from Bacillus subtilis (BFAE) and EST2 from
      Alicyclobacillus acidocaldarius, reveals an increase in the number of
      intramolecular ion pairs and secondary structure content, as well as a
      significant reduction in loop extensions and ratio of hydrophobic to charged
      surface area. The variety of structural differences suggests possible strategies
      for thermostabilization of lipases and esterases with potential industrial
      applications.

PMID- 11846564
TI  - Crystal structure of gamma-chymotrypsin in complex with 7-hydroxycoumarin.
AB  - The 1.8 A crystal structure of 7-hydroxycoumarin (7-HC) bound to chymotrypsin
      reveals that this inhibitor forms a planar cinnamate acyl-enzyme complex. The
      phenyl ring of the bound inhibitor forms numerous van der Waals contacts in the
      S1 pocket of the enzyme, with the p-hydroxyl group donating a hydrogen bond to
      the main-chain oxygen atom of Ser217, and the o-hydroxyl group forming a water
      mediated hydrogen bond with the carbonyl oxygen of Val227. The structure of the
      acyl-enzyme complex suggests that the mechanism of inhibition of 7-HC involves
      nucleophilic attack by the Ser195 O(gamma) atom on the carbonyl carbon atom of
      the inhibitor, accompanied by the breaking of the 2-pyrone ring of the inhibitor,
      and leading to the formation of a cinnamate acyl-enzyme derivative via a
      tetrahedral transition state. Comparisons with structures of photoreversible
      cinnamates bound to chymotrypsin reveal that although 7-HC interacts with the
      enzyme in a similar fashion, the binding of 7-HC to chymotrypsin takes place in a
      productive conformation in contrast to the photoreversible cinnamates. In
      summary, the 7-HC-chymotrypsin complex provides basic insight into the inhibition
      of chymotrypsin by natural coumarins and provides a structural basis for the
      design of more potent mechanism-based inhibitors against a wide range of
      biologically important chymotrypsin-like enzymes.

PMID- 11846565
TI  - Crystal structure of the non-regulatory A(4 )isoform of spinach chloroplast
      glyceraldehyde-3-phosphate dehydrogenase complexed with NADP.
AB  - Here, we report the first crystal structure of a photosynthetic glyceraldehyde-3
      phosphate dehydrogenase (GAPDH) complexed with NADP. The enzyme, purified from
      spinach chloroplasts, is constituted of a single type of subunit (A) arranged in
      homotetramers. It shows non-regulated NADP-dependent and NAD-dependent
      activities, with a preference for NADP. The structure has been solved to 3.0 A
      resolution by molecular replacement. The crystals belong to space group C222 with
      three monomers in the asymmetric unit. One of the three monomers generates a
      tetramer using the space group 222 point symmetry and a very similar tetramer is
      generated by the other two monomers, related by a non-crystallographic symmetry,
      using a crystallographic 2-fold axis. The protein reveals a large structural
      homology with known GAPDHs both in the cofactor-binding domain and in regions of
      the catalytic domain. Like all other GAPDHs investigated so far, the A(4)-GAPDH
      belongs to the Rossmann fold family of dehydrogenases. However, unlike most
      dehydrogenases of this family, the adenosine 2'-phosphate group of NADP does not
      form a salt-bridge with any positively charged residue in its surroundings, being
      instead set in place by hydrogen bonds with a threonine residue belonging to the
      Rossmann fold and a serine residue located in the S-loop of a symmetry-related
      monomer. While increasing our knowledge of an important photosynthetic enzyme,
      these results contribute to a general understanding of NADP versus NAD
      recognition in pyridine nucleotide-dependent enzymes. Although the overall
      structure of A(4)-GAPDH is similar to that of the cytosolic GAPDH from bacteria
      and eukaryotes, the chloroplast tetramer is peculiar, in that it can actually be
      considered a dimer of dimers, since monomers are bound in pairs by a disulphide
      bridge formed across Cys200 residues. This bridge is not found in other cytosolic
      or chloroplast GAPDHs from animals, bacteria, or plants other than spinach.

PMID- 11846566
TI  - Solution structure and backbone dynamics of an engineered arginine-rich subdomain
      2 of the hepatitis C virus NS3 RNA helicase.
AB  - The NS3 protein of the hepatitis C virus (HCV) is a 631 amino acid residue
      bifunctional enzyme with a serine protease localized to the N-terminal 181
      residues and an RNA helicase located in the C-terminal 450 residues. The HCV NS3
      RNA helicase consists of three well-defined subdomains which all contribute to
      its helicase activity. The second subdomain of the HCV helicase is flexibly
      linked to the remainder of the NS3 protein and could undergo rigid-body movements
      during the unwinding of double-stranded RNA. It also contains several motifs that
      are implicated in RNA binding and in coupling NTP hydrolysis to nucleic acid
      unwinding and translocation. As part of our efforts to use NMR techniques to
      assist in deciphering the enzyme's structure-function relationships and
      developing specific small molecule inhibitors, we have determined the solution
      structure of an engineered subdomain 2 of the NS3 RNA helicase of HCV, d(2Delta)
      HCVh, and studied the backbone dynamics of this protein by (15)N-relaxation
      experiments using a model-free approach. The NMR studies on this 142-residue
      construct reveal that overall subdomain 2 of the HCV helicase is globular and
      well structured in solution even in the absence of the remaining parts of the NS3
      protein. Its solution structure is very similar to the corresponding parts in the
      X-ray structures of the HCV NS3 helicase domain and intact bifunctional HCV NS3
      protein. Slow hydrogen-deuterium exchange rates map to a well-structured, stable
      hydrophobic core region away from the subdomain interfaces. In contrast, the
      regions facing the subdomain interfaces in the HCV NS3 helicase domain are less
      well structured in d(2Delta)-HCVh, show fast hydrogen-deuterium exchange rates,
      and the analysis of the dynamic properties of d(2Delta)-HCVh reveals that these
      regions of the protein show distinct dynamical features. In particular, residues
      in motif V, which may be involved in transducing allosteric effects of nucleotide
      binding and hydrolysis on RNA binding, exhibit slow conformational exchange on
      the milli- to microsecond time-scale. The intrinsic conformational flexibility of
      this loop region may facilitate conformational changes required for helicase
      function.

PMID- 11846567
TI  - Solution structures of two FHA1-phosphothreonine peptide complexes provide
      insight into the structural basis of the ligand specificity of FHA1 from yeast
      Rad53.
AB  - Rad53, a yeast checkpoint protein involved in regulating the repair of DNA
      damage, contains two forkhead-associated domains, FHA1 and FHA2. Previous
      combinatorial library screening has shown that FHA1 strongly selects peptides
      containing a pTXXD motif. Subsequent location of this motif within the sequence
      of Rad9, the target protein, coupled with spectroscopic analysis has led to
      identification of a tight binding sequence that is likely the binding site of
      FHA1: (188)SLEV(pT)EADATFVQ(200). We present solution structures of FHA1 in
      complex with this pT-peptide and with another Rad9-derived pT-peptide that has ca
      30-fold lower affinity, (148)KKMTFQ(pT)PTDPLE(160). Both complexes showed
      intermolecular NOEs predominantly between three peptide residues (pT, +1, and +2
      residues) and five FHA1 residues (S82, R83, S85, T106, and N107). Furthermore,
      the following interactions were implicated on the basis of chemical shift
      perturbations and structural analysis: the phosphate group of the pT residue with
      the side-chain amide group of N86 and the guanidino group of R70, and the
      carboxylate group of Asp (at the +3 position) with the guanidino group of R83.
      The generated structures revealed a similar binding mode adopted by these two
      peptides, suggesting that pT and the +3 residue Asp are the major contributors to
      binding affinity and specificity, while +1 and +2 residues could provide
      additional fine-tuning. It was also shown that FHA1 does not bind to the
      corresponding pS-peptides or a related pY-peptide. We suggest that
      differentiation between pT and pS-peptides by FHA1 can be attributed to
      hydrophobic interactions between the methyl group of the pT residue and the
      aliphatic protons of R83, S85, and T106 from FHA1.

PMID- 11846568
TI  - Solution structure of the yeast Rad53 FHA2 complexed with a phosphothreonine
      peptide pTXXL: comparison with the structures of FHA2-pYXL and FHA1-pTXXD
      complexes.
AB  - It was proposed previously that the FHA2 domain of the yeast protein kinase Rad53
      has dual specificity toward pY and pT peptides. The consensus sequences of pY
      peptides for binding to FHA2, as well as the solution structures of free FHA2 and
      FHA2 complex with a pY peptide derived from Rad9, have been obtained previously.
      We now report the use of a pT library to screen for binding of pT peptides with
      the FHA2 domain. The results show that FHA2 binds favorably to pT peptides with
      Ile at the +3 position. We then searched the Rad9 sequences with a pTXXI/L motif,
      and tested the binding affinity of FHA2 toward ten pT peptides derived from Rad9.
      One of the peptides, (599)EVEL(pT)QELP(607), displayed the best binding affinity
      (K(d)=12.9 microM) and the greatest chemical shift changes. The structure of the
      FHA2 complex with this peptide was then determined by solution NMR and the
      structure of the complex between FHA2 and the pY peptide (826)EDI(pY)YLD(832) was
      further refined. Structural comparison of these two complexes indicates that the
      Leu residue at the +3 position in the pT peptide and that at the +2 position in
      the pY peptide occupy a very similar position relative to the binding site
      residues from FHA2. This can explain why FHA2 is able to bind both pT and pY
      peptides. This position change from +3 to +2 could be the consequence of the size
      difference between Thr and Tyr. Further insight into the structural basis of
      ligand specificity of FHA domains was obtained by comparing the structures of the
      FHA2-pTXXL complex obtained in this work and the FHA1-pTXXD complex reported in
      the accompanying paper.

PMID- 11846569
TI  - Forces and energetics of hapten-antibody dissociation: a biased molecular
      dynamics simulation study.
AB  - The unbinding of fluorescein from the single-chain Fv fragment of the 4D5Flu
      antibody is investigated by biased molecular dynamics with an implicit solvation
      model. To obtain statistically meaningful results, a large number of unbinding
      trajectories are calculated; they involve a total simulation time of more than
      200 ns. Simulations are carried out with a time-dependent perturbation and in the
      presence of a constant force. The two techniques, which provide complementary
      information, induce unbinding by favoring an increase in the distance between the
      ligand and the antibody. This distance is an appropriate progress variable for
      the dissociation reaction and permits direct comparison of the unbinding forces
      in the simulations with data from atomic force microscopy (AFM). The time
      dependent perturbation generates unfolding pathways that are close to equilibrium
      and can be used to reconstruct the mean force; i.e. the derivative of the
      potential of mean force, along the reaction coordinate. This is supported by an
      analysis of the overall unbinding profile and the magnitude of the mean force,
      which are similar to those of the unbinding force (i.e. the external force due to
      the time-dependent perturbation) averaged over several unbinding events. The
      multiple simulations show that unbinding proceeds along a rather well-defined
      pathway for a broad range of effective pulling speeds. Initially, there is a
      distortion of the protein localized in the C-terminal region followed by the
      fluorescein exit from the binding site. This occurs in steps that involve
      breaking of specific electrostatic and van der Waals interactions. It appears
      that the simulations do not explore the same barriers as those measured in the
      AFM experiments because of the much higher unfolding speed in the former. The
      dependence of the force on the logarithm of the loading rate is linear and the
      slope is higher than in the AFM, in agreement with experiment in other systems,
      where different slopes were observed for different regimes. Based on the
      unbinding events, mutations in the 4D5Flu antigen binding site are predicted to
      result in significant changes in the unbinding force.

PMID- 11846570
TI  - Binding mode prediction for a flexible ligand in a flexible pocket using multi
      conformation simulated annealing pseudo crystallographic refinement.
AB  - We describe multi-conformation simulated annealing-pseudo-crystallographic
      refinement (MCSA-PCR), a technique developed for predicting the binding mode of a
      flexible ligand in a flexible binding pocket. To circumvent the local-minimum
      problem efficiently, this method performs multiple independent cycles of
      simulated annealing with explicit solvent, "growing" the ligand in the binding
      pocket each time. From the ensemble of structures, a pseudo-crystallographic
      electron density map is calculated, and then conventional crystallographic
      refinement methods are used to best fit a single, optimal structure into the
      density map. The advantage of the MCSA-PCR method is that it provides a direct
      means to evaluate the accuracy and uniqueness of the calculated solution,
      provides a measure of ligand and protein dynamics from the refined B-factors, and
      facilitates comparison with X-ray crystallographic data. Here, we show that our
      MCSA-PCR method succeeds in predicting the correct binding mode of the VSV8
      peptide to the major histocompatibility complex (MHC) receptor. Importantly,
      there is a significant correlation between the experimentally determined
      crystallographic water molecules and water density observed in the pseudo map by
      MCSA-PCR. Furthermore, comparison of different approaches for extracting a
      single, most probable structure from the calculated ensemble reveals the power of
      the PCR method and provides insights into the nature of the energetic landscape.

PMID- 11846571
TI  - Do water molecules mediate protein-DNA recognition?
AB  - A comprehensive analysis of interfacial water molecules in the structures of 109
      unique protein-DNA complexes is presented together with a new view on their role
      in protein-DNA recognition. Location of interfacial water molecules as reported
      in the crystal structures and as emerging from a series of molecular dynamics
      studies on protein-DNA complexes with explicit solvent and counterions, was
      analyzed based on their acceptor, donor hydrogen bond relationships with the
      atoms and residues of the macromolecules, electrostatic field calculations and
      packing density considerations. Water molecules for the purpose of this study
      have been categorized into four classes: viz. (I) those that contact both the
      protein and the DNA simultaneously and thus mediate recognition directly; (II)
      those that contact either the protein or the DNA exclusively via hydrogen bonds
      solvating each solute separately; (III) those that contact the hydrophobic groups
      in either the protein or the DNA; and, lastly (IV) those that contact another
      water molecule. Of the 17,963 crystallographic water molecules under examination,
      about 6% belong to class I and 76% belong to class II. About three-fourths of
      class I and class II water molecules are exclusively associated with hydrogen
      bond acceptor atoms of both protein and DNA. Noting that DNA is polyanionic, it
      is significant that a majority of the crystallographically observed water
      molecules as well as those from molecular dynamics simulations should be involved
      in facilitating binding by screening unfavorable electrostatics. Less than 2% of
      the reported water molecules occur between hydrogen bond donor atoms of protein
      and acceptor atoms of DNA. These represent cases where protein atoms cannot reach
      out to DNA to make favorable hydrogen bond interactions due to packing/structural
      restrictions and interfacial water molecules provide an extension to side-chains
      to accomplish hydrogen bonding.

PMID- 11846572
TI  - The structures of Escherichia coli inorganic pyrophosphatase complexed with
      Ca(2+) or CaPP(i) at atomic resolution and their mechanistic implications.
AB  - Two structures of Escherichia coli soluble inorganic pyrophosphatase (EPPase)
      complexed with calcium pyrophosphate (CaPP(i)-EPPase) and with Ca(2+) (Ca(2+)
      EPPase) have been solved at 1.2 and 1.1 A resolution, respectively. In the
      presence of Mg(2+), this enzyme cleaves pyrophosphate (PP(i)) into two molecules
      of orthophosphate (P(i)). This work has enabled us to locate PP(i) in the active
      site of the inorganic pyrophosphatases family in the presence of Ca(2+), which is
      an inhibitor of EPPase.Upon PP(i) binding, two Ca(2+) at M1 and M2 subsites move
      closer together and one of the liganded water molecules becomes bridging. The
      mutual location of PP(i) and the bridging water molecule in the presence of
      inhibitor cation is catalytically incompetent. To make a favourable PP(i) attack
      by this water molecule, modelling of a possible hydrolysable conformation of
      PP(i) in the CaPP(i)-EPPase active site has been performed. The reasons for
      Ca(2+) being the strong PPase inhibitor and the role in catalysis of each of four
      metal ions are the mechanistic aspects discussed on the basis of the structures
      described.

PMID- 11846574
TI  - System of thermostatic control on Peltier thermopiles and microprocessor control
      for a portable NMR relaxometer.
AB  - Liquid equipment for thermostatic control of samples with accuracy better than
      0.1 degree C within the temperature range from -20 to +70 degree C is designed
      for small-sized NMR spectrometers. The difficulty in using this equipment is a
      thermomodule based on the Peltier effect. The temperature control system is based
      on a single crystal microcomputer. The equipment fits modern small-sized NMR
      spectrometers, which facilitates medical and biological studies.

PMID- 11846573
TI  - NMR spectral quantitation by principal component analysis. III. A generalized
      procedure for determination of lineshape variations.
AB  - We present a general procedure for automatic quantitation of a series of spectral
      peaks based on principal component analysis (PCA). PCA has been previously used
      for spectral quantitation of a single resonant peak of constant shape but
      variable amplitude. Here we extend this procedure to estimate all of the peak
      parameters: amplitude, position (frequency), phase and linewidth. The procedure
      consists of a series of iterative steps in which the estimates of position and
      phase from one stage of iteration are used to correct the spectra prior to the
      next stage. The process is convergent to a stable result, typically in less than
      5 iterations. If desired, remaining linewidth variations can then be corrected.
      Correction of (typically) unwanted variations of these types is important not
      only for direct peak quantitation, but also as a preprocessing step for spectral
      data prior to application of pattern recognition/classification techniques. The
      procedure is demonstrated on simulated data and on a set of 992 (31)P NMR in vivo
      spectra taken from a kinetic study of rat muscle energetics. The proposed
      procedure is robust, makes very limited assumptions about the lineshape, and
      performs well with data of low signal-to-noise ratio.

PMID- 11846575
TI  - Numerical simulation of one- and two-dimensional ESEEM experiments.
AB  - Numerical simulation has become an indispensable tool for the interpretation of
      pulse EPR experiments. In this work it is shown how automatic orientation
      selection, grouping of operator factors, and direct selection and elimination of
      coherences can be used to improve the efficiency of time-domain simulations of
      one- and two-dimensional electron spin echo envelope modulation (ESEEM) spectra.
      The program allows for the computation of magnetic interactions of any symmetry
      and can be used to simulate spin systems with an arbitrary number of nuclei with
      any spin quantum number. Experimental restrictions due to finite microwave pulse
      lengths are addressed and the enhancement of forbidden coherences by microwave
      pulse matching is illustrated. A comparison of simulated and experimental HYSCORE
      (hyperfine sublevel correlation) spectra of ordered and disordered systems with
      varying complexity shows good qualitative agreement.

PMID- 11846576
TI  - Time-optimal coherence-order-selective transfer of in-phase coherence in
      heteronuclear IS spin systems.
AB  - Based on principles of geometric optimal control theory, coherence transfer
      building blocks can be derived which achieve optimal sensitivity. Here,
      experimental pulse sequences are presented that achieve the best possible
      coherence-order-selective in-phase transfer (S(-)-->I(-)) for a heteronuclear 2
      spin system for any given mixing time in the absence of relaxation. For short
      mixing times, the optimal experiment improves the sensitivity of isotropic mixing
      by up to 12.5%.

PMID- 11846577
TI  - Efficient triple-quantum excitation in modified RIACT MQMAS NMR for I=3/2 nuclei.
AB  - A new approach involving the creation of triple-quantum (TQ) coherences from both
      TQ and central transitions (CT) is investigated, in order to enhance the
      efficiency of triple-quantum excitation for I=3/2 nuclei. The RIACT excitation
      scheme, a soft pi/2 and hard spin-locking pulse, is shown to induce both
      adiabatic coherence transfer between CT and TQ coherences and TQ nutation. By
      combining the RIACT scheme with the presaturation of the satellite transitions, a
      significant improvement in the TQ excitation can be achieved mainly through
      enhanced CT polarization via the RIACT mechanism, in particular for nuclei with
      moderate to large quadrupole coupling constants (> or = 2.0 MHz). There also
      exists a nontrivial contribution from the TQ transition, which depends on the
      size of the quadrupole interaction.

PMID- 11846578
TI  - 14N chemical shifts and quadrupole coupling constants of inorganic nitrates.
AB  - The isotropic chemical shift and the nuclear quadrupole coupling constant for
      (14)N were obtained for 14 inorganic nitrates by solid-state MAS NMR measurements
      at two different field strengths, 9.4 and 11.7 T. The compounds studied were
      polycrystalline powders of AgNO(3), Al(NO(3))(3), Ba(NO(3))(2), Ca(NO(3))(2),
      CsNO(3), KNO(3), LiNO(3), Mg(NO(3))(2), NaNO(3), Pb(NO(3))(2), RbNO(3),
      Sr(NO(3))(2), Th(NO(3))(4)center dot4H(2)O, and UO(2)(NO(3))(2)center dot3H(2)O.
      Even though the spectra show broadening due to (14)N quadrupole interactions,
      linewidths of a few hundred hertz and a good signal-to-noise ratio were achieved.
      From the position of the central peaks at the two fields, the chemical shifts and
      the nuclear quadrupole coupling constants were calculated. The chemical shifts
      for all compounds studied range from 282 to 342 ppm with respect to NH(4)Cl. The
      nuclear quadrupole coupling constants range from 429 kHz for AgNO(3) to 993 kHz
      for LiNO(3). These data are compared with those available in the literature.

PMID- 11846579
TI  - Probe--sample coupling in the magnetic resonance force microscope.
AB  - The magnetic resonance force microscope (MRFM) provides a route to achieving
      scanned probe magnetic resonance imaging with extremely high spatial resolution.
      Achieving this capability will require understanding the force exerted on a
      microscopic magnetic probe by a spatially extended sample over which the probe is
      scanned. Here we present a detailed analysis of this interaction between probe
      and sample. We focus on understanding the situation where the micromagnet mounted
      on the mechanical resonator generates a very inhomogeneous magnetic field and is
      scanned over a sample with at least one spatial dimension much larger than that
      of the micromagnet. This situation differs quite significantly from the
      conditions under which most MRFM experiments have been carried out where the
      sample is mounted on the mechanical resonator and placed in a rather weak
      magnetic field gradient. In addition to the concept of a sensitive slice (the
      spatial region where the magnetic resonance condition is met) it is valuable to
      map the forces exerted on the probe by spins at various locations; this leads to
      the concept of the force slice (the region in which spins exert force on the
      resonator). Results of this analysis, obtained both analytically and numerically,
      will be qualitatively compared with an initial experimental finding from an EPR
      MRFM experiment carried out on DPPH at 4 K.

PMID- 11846580
TI  - Separation of intra- and extramyocellular lipid signals in proton MR spectra by
      determination of their magnetic field distribution.
AB  - In skeletal musculature intramyocellular (IMCL) and extramyocellular lipids
      (EMCL) are stored in compartments of different geometry and experience different
      magnetic field strengths due to geometrical susceptibility effects. The effect is
      strong enough to---at least partly---separate IMCL and EMCL contributions in (1)H
      MR spectroscopy, despite IMCL and EMCL consisting of the same substances. The
      assessment of intramyocellular lipid stores in skeletal musculature by (1)H MR
      spectroscopy plays an important role for studying physiological and pathological
      aspects of lipid metabolism. Therefore, a method using mathematical tools of
      Fourier analysis is developed to obtain the magnetic field distribution (MFD)
      from the measured spectra by deconvolution. A reference lipid spectrum is
      required which was recorded in tibial yellow bone marrow. It is shown that the
      separation of IMCL contributions can be performed more precisely---compared to
      other methods---based on the MFD. Examples of deconvolution in model systems
      elucidate the principle. Applications of the proposed approach on in vivo
      examinations in m. soleus and m. tibialis anterior are presented. Fitting the
      IMCL part of the MFD by a Gaussian lineshape with a linewidth kept fixed with
      respect to the linewidth of creatine and with the assumption of a smooth but not
      necessarily symmetrical shape for the EMCL part, the only free fit parameter, the
      amplitude of the IMCL part, is definite and subtraction leads to the EMCL part in
      the MFD. This procedure is especially justified for the soleus muscle showing a
      severely asymmetrical distribution which might lead to a marked overestimation of
      IMCL using common line fitting procedures.

PMID- 11846581
TI  - Improved narrowband dipolar recoupling for homonuclear distance measurements in
      rotating solids.
AB  - Recovery of the magnetic dipolar interaction between nuclei bearing the same
      gyromagnetic ratio in rotating solids can be promoted by synchronous rf
      irradiation. Determination of the dipolar interaction strength can serve as a
      tool for structural elucidation in polycrystalline powders. Spinning frequency
      dependent narrow-band (nb) RFDR and SEDRA experiments are utilized as simple
      techniques for the determination of dipolar interactions between the nuclei in
      coupled homonuclear spin pairs. The magnetization exchange and coherence
      dephasing due to a fixed number of rotor-synchronously applied pi-pulses is
      monitored at spinning frequencies in the vicinity of the rotational resonance
      (R(2)) conditions. The powder nbRFDR and nbSEDRA decay curves of spin
      magnetizations and coherences, respectively, as a function of the spinning
      frequency can be measured and analyzed using simple rate equations providing a
      quantitative measure of the dipolar coupling. The effects of the phenomenological
      relaxation parameters in these rate equations are discussed and an improved
      methodology is suggested for analyzing nbRFDR data for small dipolar couplings.
      The distance between the labeled nuclei in the 1,3-(13)C(2)-hydroxybutyric acid
      molecule is rederived using existing nbRFDR results and the new simulation
      procedure. A nbSEDRA experiment has been performed successfully on a powder
      sample of singly labeled 1-(13)C-L-leucine measuring the dipolar interaction
      between the labeled carboxyl carbon and the natural abundant beta-carbon. Both
      narrowband techniques are employed for the determination of the nuclear distances
      between the side-chain carbons of leucine and its carbonyl carbon in a tripeptide
      Leu-Gly-Phe that is singly (13)C-labeled at the leucine carbonyl carbon position.

PMID- 11846582
TI  - GAMMA simulations of stray field responses: slice thickness and pulse
      calibration.
AB  - A stray field (STRAFI) module has been added to the GAMMA magnetic resonance
      simulation platform in order to facilitate computational investigations of NMR
      experiments in large static field gradients that are on the order of 50 T/m. The
      package has been used to examine system response during echo trains generated by
      the application of shaped pulses. The associated echo amplitude maxima and
      effective slice thickness are presented. A new accurate method for STRAFI pulse
      calibration based on relative echo amplitudes is proposed.

PMID- 11846583
TI  - T(1)--T(2) correlation spectra obtained using a fast two-dimensional Laplace
      inversion.
AB  - Spin relaxation is a sensitive probe of molecular structure and dynamics.
      Correlation of relaxation time constants, such as T(1) and T(2), conceptually
      similar to the conventional multidimensional spectroscopy, have been difficult to
      determine primarily due to the absense of an efficient multidimensional Laplace
      inversion program. We demonstrate the use of a novel computer algorithm for fast
      two-dimensional inverse Laplace transformation to obtain T(1)--T(2) correlation
      functions. The algorithm efficiently performs a least-squares fit on two
      dimensional data with a nonnegativity constraint. We use a regularization method
      to find a balance between the residual fitting errors and the known noise
      amplitude, thus producing a result that is found to be stable in the presence of
      noise. This algorithm can be extended to include functional forms other than
      exponential kernels. We demonstrate the performance of the algorithm at different
      signal-to-noise ratios and with different T(1)--T(2) spectral characteristics
      using several brine-saturated rock samples.

PMID- 11846584
TI  - Closed-form expressions for level-averaged electron spin relaxation times outside
      the Zeeman limit: application to paramagnetic NMR relaxation.
AB  - Paramagnetic enhancement of NMR relaxation (NMR-PRE) depends on thermal
      relaxation of the electron spin system. Most previous analyses of experimental
      NMR-PRE data have relied on Bloembergen--Morgan (B--M) theory to describe the
      magnetic field dependence of electron spin relaxation in liquid samples. However,
      B--M theory assumes a Zeeman-limit situation and is not physically appropriate to
      the common case of S > or = 1 transition metal ions which possess a permanent
      zero-field splitting (zfs) that is comparable to or larger than the Zeeman
      splitting. Theory has been needed which (1) includes the effects of the zfs
      interaction, thus providing a realistic description of the magnetic field
      dependence of the NMR-PRE outside the Zeeman limit, and (2) describes electron
      spin relaxation phenomena at a comparable level of complexity to that of B--M
      theory, i.e., with two magnetic field-dependent electron spin relaxation times,
      tau(S1) and tau(S2), defined in the laboratory coordinate frame. Theory of this
      kind is developed. Expressions derived in a previous study (R. R. Sharp and L. L.
      Lohr, J. Chem. Phys. 115, 5005 (2001).) for level-specific relaxation rates have
      been averaged over spin eigenstates to give level-averaged quantities, tau(S1,2).
      This kind of averaging leads to a great simplification in the mathematical form
      of the results. Simple zfs-limit molecular-frame and laboratory-frame expressions
      are given for electron spin S=1, 3/2, 2, and 5/2. General expressions, valid for
      S > or = 1 and for arbitrary magnitudes of the Zeeman and zfs energies, are
      derived for level-averaged electron spin relaxation times defined in both the
      laboratory- and the molecule-fixed coordinate frames. The new theory coincides
      with B--M theory in the Zeeman limit.

PMID- 11846585
TI  - Signal enhancement in 5QMAS spectra of spin-5/2 quadrupolar nuclei.
AB  - 5QMAS experiments on spin-5/2 systems display a low sensitivity compared with
      their 3QMAS counterparts. Nevertheless, the superior resolution of 5QMAS over
      3QMAS makes these experiments a favorable choice for many materials. We report an
      enhancement scheme for the 5QMAS experiment, using an improved five-quantum
      excitation pulse scheme combined with a FAM-II conversion pulse. The results are
      verified experimentally on a polycrystalline sample of gamma-(27)Al(2)O(3),
      showing an enhancement factor of 2.4 over the simple two-pulse (CW) 5QMAS scheme.
      Numerical computations of the efficiency parameter epsilon support these results.

PMID- 11846586
TI  - Evaluation and comparison of pulsed and continuous wave radiofrequency electron
      paramagnetic resonance techniques for in vivo detection and imaging of free
      radicals.
AB  - The performance of two electron paramagnetic resonance (EPR)
      spectrometers/imagers, one configured in pulsed mode and the other in continuous
      wave (CW) mode, at an operating frequency of 300 MHz is compared. Using the same
      resonator (except for altered Q-factors), identical samples and filling factors
      in the two techniques have been evaluated for their potentials and limitations
      for in vivo spectroscopic and imaging applications. The assessment is based on
      metrics such as sensitivity, spatial and temporal resolution, field of view,
      image artifacts, viable spin probes, and subjects of study. The spectrometer dead
      time limits the pulsed technique to samples with long phase memories (>275 ns).
      Nevertheless, for viable narrow-line spin probes, the pulsed technique offers
      better sensitivity and temporal resolution. The CW technique, on the other hand,
      does not restrict the choice at spin probes. In addition, the phase-sensitive
      narrow-band detection of the CW technique gives artifact-free images even for
      large objects. Selected examples illustrating the performance of the CW and
      pulsed techniques are presented to put the capabilities of the two techniques in
      perspective.

PMID- 11846587
TI  - An open magnet utilizing ferro-refraction current magnification.
AB  - Ferro-refraction is the field magnification that is obtained when a current
      segment is near a high magnetic permeable boundary. It is shown that ferro
      refraction may be used in the design of magnets for NMR or MRI to increase the
      efficiency of these magnets. The field may be modeled analytically with the Biot-
      Savart law and the inclusion of mirror image currents. Ferro-refraction is
      particularly useful in the design of monohedral magnets, magnets producing a
      remote homogeneous region which have the magnetic sources arranged to one side.
      These magnets have also been called planar magnets. Two designs for a monohedral
      magnet which produce good agreement between experimental and analytic results are
      presented.

PMID- 11846588
TI  - Selective detection of the proton NMR spectra of molecules containing rare spins
      at natural abundance in liquid crystalline samples.
AB  - It is shown that the proton NMR spectra of molecules containing rare spins at
      natural abundance dissolved in a liquid crystalline solvent can be obtained free
      from the strong lines from the spectrum of the abundant isotopomer by the 2D HSQC
      NMR experiment. The technique can also give the individual chemical shifts of the
      rare spins, and, for a molecule containing another abundant nucleus, such as
      fluorine, the rare spin--(19)F total anisotropic couplings are also obtained. The
      usefulness of the technique is demonstrated for molecules containing (13)C as the
      rare spins.

PMID- 11846589
TI  - NMR velocimetry of falling liquid films.
AB  - First results on NMR velocimetry of falling liquid films are presented. A film of
      average thickness 1 mm and width 40 mm is sustained by a continuous flow of
      silicon oil over a vertical plate made from PMMA. The spatial distribution of
      velocities is measured using a double spin--echo imaging pulse sequence
      supplemented by a bipolar velocity encoding gradient. Spin density and velocity
      images as well as two-dimensional velocity maps of different situations, i.e.,
      undisturbed and disturbed falling film flow, are discussed. Experimental and
      theoretical velocity data for undisturbed film flow are compared.

PMID- 11846590
TI  - NMR determination of the torsion angle psi in alpha-helical peptides and
      proteins: the HCCN dipolar correlation experiment.
AB  - Several existing methods permit measurement of the torsion angles phi, psi and
      chi in peptides and proteins with solid-state MAS NMR experiments. Currently,
      however, there is not an approach that is applicable to measurement of psi in the
      angular range -20 degree to -70 degree, commonly found in alpha-helical
      structures. Accordingly, we have developed a HCCN dipolar correlation MAS
      experiment that is sensitive and accurate in this regime. An initial REDOR driven
      (13)C'--(15)N dipolar evolution period is followed by the C' to C(alpha)
      polarization transfer and by Lee--Goldburg cross polarization recoupling of the
      (13)C(alpha)(1)H dipolar interaction. The difference between the effective
      (13)C(1)H and (13)C(15)N dipolar interaction strengths is balanced out by
      incrementing the (13)C--(15)N dipolar evolution period in steps that are a factor
      of R(R approximately omega(CH)/omega(CN)) larger than the (13)C--(1)H steps. The
      resulting dephasing curves are sensitive to variations in psi in the angular
      region associated with alpha-helical secondary structure. To demonstrate the
      validity of the technique, we apply it to N-formyl-[U-(13)C,(15)N] Met-Leu-Phe-OH
      (MLF). The value of psi extracted is consistent with the previous NMR
      measurements and close to that reported in diffraction studies for the methyl
      ester of MLF, N-formyl-[U-(13)C,(15)N]Met-Leu-Phe-OMe.

PMID- 11846591
TI  - A new method for variable temperature gradient shimming.
AB  - Sample convection can severely attenuate the signals observed in pulsed field
      gradient spin--echo experiments such as those used for gradient shimming. A new
      class of pulse sequences is proposed, in which a double spin--echo refocuses the
      phase errors caused by sample convection, enabling gradient shimming to be
      performed reliably over a wide range of temperatures.

PMID- 11846592
TI  - Using conjoined rigid body/torsion angle simulated annealing to determine the
      relative orientation of covalently linked protein domains from dipolar couplings.
AB  - A simple and robust method for determining the relative orientations of
      covalently linked protein domains using conjoined rigid body/torsion angle
      dynamics simulated annealing on the basis of residual dipolar couplings is
      presented. In this approach each domain is treated as a rigid body and the
      relevant degrees of conformational freedom are restricted to the backbone torsion
      angles (phi, psi) of the linker between the domains. By this means translational
      information afforded by the presence of an intact linker is preserved. We
      illustrate this approach using the domain-swapped dimer of the HIV-inactivating
      protein cyanovirin-N as an example.

PMID- 11846593
TI  - Picoliter (1)H NMR spectroscopy.
AB  - In this study, a 267-microm-diameter solenoid transceiver is used to acquire
      localized (1)H NMR spectra and the measured signal-to-noise ratio (SNR) at 500
      MHz is shown to be within 20--30% of theoretical limits formulated by considering
      only its resistive losses. This is illustrated using a 100-microm-diameter
      globule of triacylglycerols (approximately 900mM) that may be an oocyte precursor
      in young Xenopus laevis frogs and a water sample containing choline at a
      concentration often found in live mammalian cells (approximately 33 mM). In
      chemical shift imaging (CSI) experiments performed using a few thousand total
      scans, the choline methyl line is shown to have an acceptable SNR in resolved
      volume elements containing only 50 pL of sample, and localized spectra are
      resolved from just 5 pL in the Xenopus globule. These findings demonstrate the
      feasibility of performing (1)H NMR on picoliter-scale sample volumes in
      biological cells and tissues and illustrate how the achieved SNR in spectroscopic
      images can be predicted with reasonable accuracy at microscopic spatial
      resolutions.

PMID- 11846594
TI  - The ESS in an asymmetric generalized war of attrition with mistakes in role
      perception.
AB  - We derive the ESS for the generalized asymmetric war of attrition, where payoffs
      to contestants may vary in time and may depend on some characteristic, called the
      "role" of an individual. We use the same approach as Hammerstein & Parker (1982),
      who examined an asymmetric war of attrition. We consider two roles, A and B. Role
      A is assumed to be favoured with respect to payoffs. It is assumed that there is
      always a true asymmetry, so in each contest one individual has role A and the
      other has role B. It is assumed that roles are assigned to contestants at random
      and that they can make mistakes in role perception. It is shown that, under
      certain assumptions about shapes of payoff functions and probabilities of making
      mistakes, there is an ESS which can be characterized by two probability
      distributions with non-overlapping support. Individuals who perceive their role
      as A should choose larger persistence times. This ESS structure is similar to
      that in the asymmetric war of attrition. In that model, the resource values and
      the cost rates are constant. We consider situations where all these values may
      change in time and where rewards and costs may be equal after some finite time.
      Such shapes of payoff functions arise naturally in competitive patch depletion
      (Sjerps & Haccou, 1994a,b). As a result, the probability density functions that
      specify the conditional strategies are no longer necessarily negative
      exponentials (as in the war of attrition), but may have very different shapes.
      Furthermore, under some conditions there is a maximum persistence time, at which
      there can be an atom of probability. We give explicit expressions as well as
      numerical approximations for the ESS.

PMID- 11846595
TI  - Animal flight dynamics II. Longitudinal stability in flapping flight.
AB  - Stability is essential to flying and is usually assumed to be especially
      problematic in flapping flight. If so, problems of stability may have presented a
      particular hurdle to the evolution of flapping flight. In spite of this, the
      stability of flapping flight has never been properly analysed. Here we use quasi
      static and blade element approaches to analyse the stability provided by a
      flapping wing. By using reduced order approximations to the natural modes of
      motion, we show that wing beat frequencies are generally high enough compared to
      the natural frequencies of motion for a quasi-static approach to be valid as a
      first approximation. Contrary to expectations, we find that there is noting
      inherently destabilizing about flapping: beating the wings faster simply
      amplifies any existing stability or instability, and flapping can even enhance
      stability compared to gliding at the same air speed. This suggests that
      aerodynamic stability may not have been a particular hurdle in the evolution of
      flapping flight. Hovering animals, like hovering helicopters, are predicted to
      possess neutral static stability. Flapping animals, like fixed wing aircraft, are
      predicted to be stable in forward flight if the mean flight force acts above
      and/or behind the centre of gravity. In this case, the downstroke will always be
      stabilizing. The stabilizing contribution may be diminished by an active upstroke
      with a low advance ratio and more horizontal stroke plane; other forms of the
      upstroke may make a small positive contribution to stability. An active upstroke
      could, therefore, be used to lower stability and enhance manoeuvrability.
      Translatory mechanisms of unsteady lift production are predicted to amplify the
      stability predicted by a quasi-static analysis. Non-translatory mechanisms will
      make little or no contribution to stability. This may be one reason why flies,
      and other animals which rely upon non-translatory aerodynamic mechanisms, often
      appear inherently unstable.

PMID- 11846596
TI  - Order and flexibility in the motion of fish schools.
AB  - The coexistence of order and flexibility in the motion of fish schools was
      studied by using a simple numerical model and a computer simulation. The
      numerical model is based on behavioral rules for individuals in the school by
      considering attraction, repulsion, and parallel-orientation behavior. Each
      individual follows the same rules and makes school movements. The simulation
      results show that school order and flexibility are affected by the number of
      neighbors interacting with an individual in the school and by the randomness of
      individual motion. Increase in the number of interacting neighbors leads to high
      order, especially when the number increases from a low value (between one and
      three). An optimal number of interacting neighbors exists that is relatively low
      (two or three) for high flexibility, indicating that a fish needs only to pay
      attention to a few neighbors to realize both order and flexibility. The low
      randomness of individual motion benefits both order and flexibility. These
      results indicate that schooling fish have evolved specialized ability for
      establishing both school order and flexibility.

PMID- 11846597
TI  - Intensity generalization: physiology and modelling of a neglected topic.
AB  - I briefly review empirical data about the generalization of acquired behaviour to
      novel stimuli, showing that variations in stimulus intensity affect behaviour
      differently from variations in characteristics such as, for instance, visual
      shape or sound frequency. I argue that such differences can be seen already in
      how the sense organs react to changes in intensity compared to changes in other
      stimulus characteristics. I then evaluate a number of models of generalization
      with respect to their ability to reproduce intensity generalization. I reach
      three main conclusions. First, realistic stimulus representations, based on
      knowledge of the sense organs, are necessary to account for intensity effects.
      Models employing stimulus representations too remote from the sense organs are
      unable to reproduce the data. Second, the intuitive notion that generalization is
      based on similarities between stimuli, possibly modelled as distances in an
      appropriate representation space, is difficult to reconcile with data about
      intensity generalization. Third, several simple models, in conjunction with
      realistic stimulus representations, can account for a wide array of
      generalization phenomena along both intensity and non-intensity stimulus
      dimensions. The paper also introduces concepts which may be generally useful to
      evaluate and compare different models of behaviour.

PMID- 11846598
TI  - Small world patterns in food webs.
AB  - The analysis of some species-rich, well-defined food webs shows that they display
      the so-called small world behavior shared by a number of disparate complex
      systems. The three systems analysed (Ythan estuary web, Silwood web and the
      Little Rock lake web) have different levels of taxonomic resolution, but all of
      them involve high clustering and short path lengths (near two degrees of
      separation) between species. Additionally, the distribution of connections P(k)
      which is skewed in all the webs analysed shows long tails indicative of power-law
      scaling. These features suggest that communities might be self-organized in a non
      random fashion that might have important consequences in their resistance to
      perturbations (such as species removal). The consequences for ecological theory
      are outlined.

PMID- 11846600
TI  - Using the volumetric indices of telencephalic structures to distinguish
      Salamandridae and Plethodontidae: comparison of three statistical methods.
AB  - The aim of this study was to establish whether appropriate statistical analysis
      of 16 volumetric indices corresponding to 16 structures making up the entire
      telencephalon of Urodela could distinguish between two families, Salamandridae
      and Plethodontidae. We compared the efficiency of three statistical methods
      (stepwise discriminant analysis, artificial neural networks, correspondence
      factor analysis) and the information they provide. All three methods found the
      same species difficult to classify. However, only correspondence factor analysis
      could suggest explanations for "misclassifications" as it superimposes the two
      sets of variables, (sub)species and anatomical variables, thus revealing the
      correlations between them. The bulbus olfactorius accessorius and the caudal
      mitral cell layer of the bulbus olfactorius principalis were the most
      discriminatory structures in separating Salamandridae and Plethodontidae. The
      correspondence factor analysis mapped species very much in line with accepted
      taxonomy and highlighted several current controversies [e.g. positioning of
      certain newts (T. marmoratus, T. vulgaris, T. alpestris), of Salamandrina
      terdigitata, and of members of the genus Euproctus]. Mapping of Plethodontidae
      was less clear-cut than that of Salamandridae with more overlap among genera but
      was quite consistent with knowledge of brain structure complexification. We
      conclude that relationships derived from analyses of telencephalic structures
      provide valuable information that might help resolve ambiguities; we have coined
      the term "neurotaxonomy" for this approach.

PMID- 11846599
TI  - Thermal environment and human birth weight.
AB  - Human birth weight is known to be influenced by several factors, including
      maternal energy supply, maternal stature, disease status, smoking status and
      gestation length. This article proposes that the thermal environment may be a
      further factor influencing birth weight. Experimental animal studies demonstrate
      clear effects of thermal stress on placental function and birth weight, but may
      have limited relevance for humans due to between-species differences in pregnancy
      physiology. Observational studies suggest an inverse relationship between
      environmental temperature and birth weight within and between human populations.
      Variation in maternal size, body fatness, pregnancy weight gain and heat
      production is predicted to influence maternal thermoregulatory capacity, as are
      the size and composition of the foetus. These associations generate the
      hypothesis that low birth weight in hot environments may in part represent an
      adaptation to environmental heat stress.

PMID- 11846601
TI  - Swarming strategies for cooperative species.
AB  - In this paper, we propose a model to investigate the relative efficiency of
      simple swarming strategies based on the interplay between spontaneous and
      recruitment-based emigration. We conduct a dynamical study of the model which
      combines inverse density dependence, saturation effects and induced vs. diffusion
      like population transfer. The influence of the most relevant parameters is
      explored on a systematic basis, and transition values for which qualitative
      changes occur in the system's behaviour are given. The model is then used to
      study colonization of a multiple sites environment, as well as confrontation
      between species featuring different swarming strategies. Simulation results
      indicate that cooperative organisms should have an interest in evolving
      recruitment-based emigration. The corresponding population transfer patterns
      prove more efficient in invading new territories, eliminating competitors in the
      process. We suggest that this advantage could have promoted a simple form of
      coordinated swarming in species featuring a primitive type of cooperation.

PMID- 11846602
TI  - The different effects of apoptosis and DNA repair on tumorigenesis.
AB  - Complex multicellular organisms have evolved mechanisms to ensure that individual
      cells follow their proper developmental and somatic programs. Tumorigenesis, or
      uncontrolled cellular proliferation, is caused by somatic mutations to those
      genetic constraints that normally operate within a tissue. Genes involved in DNA
      repair and apoptosis are particularly instrumental in safeguarding cells against
      tumorigenesis. In this paper, we introduce a stochastic framework to analyse the
      somatic evolution of cancer initiation. Within this model, we study how apoptosis
      and DNA repair can maintain the transient stability of somatic cells and delay
      the onset of cancer. Focusing on individual cell lineages, we calculate the
      waiting time before tumorigenesis in the presence of varying degrees of apoptosis
      and DNA repair. We find that the loss of DNA repair or the loss of apoptosis both
      hasten tumorigenesis, but in characteristically different ways.

PMID- 11846603
TI  - The follicular automaton model: effect of stochasticity and of synchronization of
      hair cycles.
AB  - Human scalp hair consists of a set of about 10(5)follicles which progress
      independently through developmental cycles. Each hair follicle successively goes
      through the anagen (A), catagen (C), telogen (T) and latency (L) phases that
      correspond, respectively, to growth, arrest and hair shedding before a new anagen
      phase is initiated. Long-term experimental observations in a group of ten male,
      alopecic and non-alopecic volunteers allowed determination of the characteristics
      of hair follicle cycles. On the basis of these observations, we previously
      proposed a follicular automaton model to simulate the dynamics of human hair
      cycles and the development of different patterns of alopecia [Halloy et al.
      (2000) Proc. Natl Acad. Sci. U.S.A.97, 8328-8333]. The automaton model is defined
      by a set of rules that govern the stochastic transitions of each follicle between
      the successive states A, T, L and the subsequent return to A. These transitions
      occur independently for each follicle, after time intervals given stochastically
      by a distribution characterized by a mean and a standard deviation. The
      follicular automaton model was shown to account both for the dynamical
      transitions observed in a single follicle, and for the behaviour of an ensemble
      of independently cycling follicles. Here, we extend these results and investigate
      additional properties of the model. We present a deterministic version of the
      follicular automaton. We show that numerical simulations of the stochastic
      version of the automaton yield steady-state level of follicles in the different
      phases which approach the levels predicted by the deterministic equations as the
      number of follicles progressively increases. Only the stochastic version can
      successfully reproduce the fluctuations of the fractions of follicles in each of
      the three phases, observed in small follicle populations. When the standard
      deviation is reduced or when the follicles become otherwise synchronized, e.g. by
      a periodic external signal inducing the transition of anagen follicles into
      telogen phase, large-amplitude oscillations occur in the fractions of follicles
      in the three phases. These oscillations are not observed in humans but are
      reminiscent of the phenomenon of moulting observed in a number of mammalian
      species.

PMID- 11846604
TI  - Generalized Munch coupling between sugar and water fluxes for modelling carbon
      allocation as affected by water status.
AB  - A model of within-plant carbon allocation is proposed which makes a generalized
      use of the Munch mechanism to integrate carbon and water functions and their
      involvement in growth limitations. The plant is envisioned as a branched network
      of resistive pathways (phloem and xylem) with nodal organs acting as sources and
      sinks for sucrose. Four elementary organs (leaf, stem, fruit, root) are described
      with their particular sink functions and hydraulic attributes. Given the rates of
      photosynthesis and transpiration and the hydraulic properties of the network as
      inputs, the model calculates the internal fluxes of water and sucrose. Xylem
      water potential (Psi), phloem sucrose concentration (C) and turgor pressure (P)
      are calculated everywhere in the network accounting for osmotic equilibrium
      between apoplasm and symplasm and coupled functioning of xylem and phloem. The
      fluxes of phloem and xylem saps are driven by the gradients of P and Psi,
      respectively. The fruit growth rate is assumed as turgor pressure dependent. To
      demonstrate its ability to address within-plant competition, the model is run
      with a simple-branched structure gathering three leaves, eight stem segments,
      three competing growing fruits and one root. The model was programmed with P
      Spice, a software specifically designed for simulating electrical circuits but
      easily adaptable to physiology. Simulations of internal water fluxes, sucrose
      concentrations and fruit growth rates are given for different conditions of soil
      water availability and hydraulic resistances (sensitivity analysis). The
      discussion focuses on the potential interest of this approach in functional-
      structural plant models to address water stress-induced effects.

PMID- 11846605
TI  - A general model for host plant selection in phytophagous insects.
AB  - We develop a general theoretical framework for exploring the host plant selection
      behaviour of herbivorous insects. This model can be used to address a number of
      questions, including the evolution of specialists, generalists, preference
      hierarchies, and learning. We use our model to: (i) demonstrate the consequences
      of the extent to which the reproductive success of a foraging female is limited
      by the rate at which they find host plants (host limitation) or the number of
      eggs they carry (egg limitation); (ii) emphasize the different consequences of
      variation in behaviour before and after landing on (locating) a host (termed pre-
      and post-alighting, respectively); (iii) show that, in contrast to previous
      predictions, learning can be favoured in post-alighting behaviour--in particular,
      individuals can be selected to concentrate oviposition on an abundant low-quality
      host, whilst ignoring a rare higher-quality host; (iv) emphasize the importance
      of interactions between mechanisms in favouring specialization or learning.

PMID- 11846606
TI  - A comment on amplification and spread of viruses in a growing plaque.

PMID- 11846607
TI  - Real-time quantitative PCR.

PMID- 11846608
TI  - An overview of real-time quantitative PCR: applications to quantify cytokine gene
      expression.
AB  - The analysis of cytokine profiles helps to clarify functional properties of
      immune cells, both for research and for clinical diagnosis. The real-time reverse
      transcription polymerase chain reaction (RT-PCR) is becoming widely used to
      quantify cytokines from cells, body fluids, tissues, or tissue biopsies. Being a
      very powerful and sensitive method it can be used to quantify mRNA expression
      levels of cytokines, which are often very low in the tissues under investigation.
      The method allows for the direct detection of PCR product during the exponential
      phase of the reaction, combining amplification and detection in one single step.
      In this review we discuss the principle of real-time RT-PCR, the different
      methodologies and chemistries available, the assets, and some of the pitfalls.
      With the TaqMan chemistry and the 7700 Sequence Detection System (Applied
      Biosystems), validation for a large panel of murine and human cytokines and other
      factors playing a role in the immune system is discussed in detail. In summary,
      the real-time RT-PCR technique is very accurate and sensitive, allows a high
      throughput, and can be performed on very small samples; therefore it is the
      method of choice for quantification of cytokine profiles in immune cells or
      inflamed tissues.

PMID- 11846609
TI  - Analysis of relative gene expression data using real-time quantitative PCR and
      the 2(-Delta Delta C(T)) Method.
AB  - The two most commonly used methods to analyze data from real-time, quantitative
      PCR experiments are absolute quantification and relative quantification. Absolute
      quantification determines the input copy number, usually by relating the PCR
      signal to a standard curve. Relative quantification relates the PCR signal of the
      target transcript in a treatment group to that of another sample such as an
      untreated control. The 2(-Delta Delta C(T)) method is a convenient way to analyze
      the relative changes in gene expression from real-time quantitative PCR
      experiments. The purpose of this report is to present the derivation,
      assumptions, and applications of the 2(-Delta Delta C(T)) method. In addition, we
      present the derivation and applications of two variations of the 2(-Delta Delta
      C(T)) method that may be useful in the analysis of real-time, quantitative PCR
      data.

PMID- 11846611
TI  - Quantitation of viral load using real-time amplification techniques.
AB  - Real-time PCR amplification techniques are currently used to determine the viral
      load in clinical samples for an increasing number of targets. Real-time PCR
      reduces the time necessary to generate results after amplification. In-house
      developed PCR and nucleic acid sequence-based amplification (NASBA)-based systems
      combined with several detection strategies are being employed in a clinical
      diagnostic setting. The importance of these assays in disease management is still
      in an exploration phase. Although these technologies have the implicit capability
      of accurately measuring DNA and RNA in clinical samples, issues related to
      standardization and quality control must be resolved to enable routine
      implementation of these technologies in molecular diagnostics.

PMID- 11846610
TI  - Real-time PCR analysis of DNA and RNA extracted from formalin-fixed and paraffin
      embedded biopsies.
AB  - The archives of departments of pathology represent a unique source of
      morphologically defined biopsies derived from normal and pathologically altered
      tissues for which extensive clinical data are available. The exact quantification
      of nucleic acids in these biopsies offers a promising extension of current
      methodology to study the pathogenesis of many different diseases. The development
      of real-time PCR technology has greatly facilitated the realization of nucleic
      acid quantification. Now it is feasible to analyze large series of samples for
      the exact quantification of nucleic acids even if the number of target molecules
      is small and the amount of material available for analysis is limiting. This
      review focuses on our own experiences concerning the extraction of nucleic acids
      from fixed and embedded biopsies using both conventional approaches and laser
      assisted microdissection and the subsequent application of real-time PCR methods
      for quantification of mRNA transcripts, gene copy number, and the methylation
      status. We provide a number of protocols to assist in the application of these
      techniques.

PMID- 11846612
TI  - Real-time multiplex PCR assays.
AB  - The ability to multiplex PCR by probe color and melting temperature (T(m))
      greatly expands the power of real-time analysis. Simple hybridization probes with
      only a single fluorescent dye can be used for quantification and allele typing.
      Different probes are labeled with dyes that have unique emission spectra.
      Spectral data are collected with discrete optics or dispersed onto an array for
      detection. Spectral overlap between dyes is corrected by using pure dye spectra
      to deconvolute the experimental data by matrix algebra. Since fluorescence is
      temperature dependent and depends on the dye, spectral overlap and color
      compensation constants are also temperature dependent. Single-labeled probes are
      easier to synthesize and purify than more complex probes with two or more dyes.
      In addition, the fluorescence of single-labeled probes is reversible and depends
      only on hybridization of the probe to the target, allowing study of the melting
      characteristics of the probe. Although melting curves can be obtained during PCR,
      data are usually acquired at near-equilibrium rates of 0.05-0.2 degrees C/s after
      PCR is complete. Using rapid-cycle PCR, amplification requires about 20 min
      followed by a 10-min melting curve, greatly reducing result turnaround time. In
      addition to dye color, melting temperature can be used for a second dimension of
      multiplexing. Multiplexing by color and T(m) creates a "virtual" two-dimensional
      multiplexing array without the need for an immobilized matrix of probes. Instead
      of physical separation along the X and Y axes, amplification products are
      identified by different fluorescence spectra and melting characteristics.

PMID- 11846613
TI  - Use of real-time quantitative PCR to validate the results of cDNA array and
      differential display PCR technologies.
AB  - Real-time reverse transcription polymerase chain reaction (RT-PCR) methods that
      monitor product accumulation were adapted for the validation of differentially
      expressed genes. We describe a real-time quantitative PCR assay that uses SYBR
      Green I dye-based detection and product melting curve analysis to validate
      differentially expressed genes identified by gene expression profiling
      technologies. Since SYBR Green I dye is a nonspecific intercalating dye, the
      reaction is made specific by using "hot-start" PCR and empirically determined
      annealing and signal acquisition temperatures for each gene-specific primer.
      Relative expression levels were quantified by constructing a standard curve using
      cDNA dilutions of a highly expressed gene. Using this approach, real-time PCR
      validated 17 of 21 (71%) genes identified by DNA arrays, and all but 1 of 13
      (91%) genes identified by differential display PCR (DD-PCR). Validation of
      differentially expressed genes detected by array analysis was related to
      hybridization intensity. Real-time RT-PCR results suggest that genes identified
      by DNA arrays with a two to fourfold difference in expression cannot be accepted
      as true or false without validation. Validation of differentially expressed genes
      detected by DD-PCR was not affected by band intensities. Regardless of the gene
      expression profiling technology (microarrays, DD-PCR, serial analysis of gene
      expression and subtraction hybridization), once the sequence of gene of interest
      is known, the real-time RT-PCR approach is well suited for validation of
      differential expression since it is quantitative and rapid and requires 1000-fold
      less RNA than conventional assays.

PMID- 11846614
TI  - Rapid allelic discrimination from real-time DNA amplification.
AB  - A rapid method based on fluorescence resonance energy transfer and real-time
      polymerase chain reaction (PCR) is used to identify the Factor V genotype or to
      identify the bacterial species Bartonella qunitana or Bartonella henselae.
      Allelic discrimination was performed on the post-PCR product. Thermal cyclers
      other than the 7700 sequence detection system can be used for PCR, after which
      the products can be transferred to the 7700 sequence detection system for
      measurement of fluorescence. The Delta R (the change in fluorescence) for each
      dye can be collected at the final thermal cycle and an xy scatterplot used to
      identify the specific genotype based on graph location. There are many advantages
      to this method. A maximum of 96 samples can be genotyped in less than 2 h. The
      method tolerates a wide range of DNA concentrations and can be determined without
      prior DNA determination. Fluorescence is very sensitive, with a low failure rate
      for allelic discrimination.

PMID- 11846615
TI  - DNA methylation analysis by MethyLight technology.
AB  - MethyLight is a sensitive, fluorescence-based real-time PCR technique that is
      capable of quantitating DNA methylation at a particular locus by using DNA
      oligonucleotides that anneal differentially to bisulfite-converted DNA according
      to the methylation status in the original genomic DNA. The use of three
      oligonucleotides (forward and reverse primers, and interpositioned probe) in
      MethyLight, any one or more of which can be used for methylation discrimination,
      allows for a high degree of specificity, sensitivity, and flexibility in
      methylation detection.

PMID- 11846616
TI  - Using molecular beacons to detect single-nucleotide polymorphisms with real-time
      PCR.
AB  - Detection of single-nucleotide polymorphisms (SNPs) in high-throughput studies
      promises to be an expanding field of molecular medicine in the near future.
      Highly specific, simple, and accessible methods are needed to meet the rigorous
      requirements of single-nucleotide detection needed in pharmacogenomic studies,
      linkage analysis, and the detection of pathogens. Molecular beacons present such
      a solution for the high-throughput screening of SNPs in homogeneous assays using
      the polymerase chain reaction (PCR). Molecular beacons are probes that fluoresce
      on hybridization to their perfectly complementary targets. In recent years they
      have emerged as a leading genetic analysis tool in a wide range of contexts from
      quantification of RNA transcripts, to probes on microarrays, to single-nucleotide
      polymorphism detection. The majority of these methods use PCR to obtain
      sufficient amounts of sample to analyze. The use of molecular beacons with other
      amplification schemes has been reliably demonstrated, though PCR remains the
      method of choice. Here we discuss and present how to design and use molecular
      beacons to achieve reliable SNP genotyping and allele discrimination in real-time
      PCR. In addition, we provide a new means of analyzing data outputs from such real
      time PCR assays that compensates for differences between sample condition, assay
      conditions, variations in fluorescent signal, and amplification efficiency. The
      mechanisms by which molecular beacons are able to have extraordinary specificity
      are also presented.

PMID- 11846617
TI  - Potential clinical applications of poly(ADP-ribose) polymerase (PARP) inhibitors.
AB  - Poly(ADP-ribose) polymerases (PARPs) are defined as cell signaling enzymes that
      catalyze the transfer of ADP-ribose units from NAD(+)to a number of acceptor
      proteins. PARP-1, the best characterized member of the PARP family, that
      presently includes six members, is an abundant nuclear enzyme implicated in
      cellular responses to DNA injury provoked by genotoxic stress (oxygen radicals,
      ionizing radiations and monofunctional alkylating agents). Due to its involvement
      either in DNA repair or in cell death, PARP-1 is regarded as a double-edged
      regulator of cellular functions. In fact, when the DNA damage is moderate, PARP-1
      participates in the DNA repair process. Conversely, in the case of massive DNA
      injury, elevated PARP-1 activation leads to rapid NAD(+)/ATP consumption and cell
      death by necrosis. Excessive PARP-1 activity has been implicated in the
      pathogenesis of numerous clinical conditions such as stroke, myocardial
      infarction, shock, diabetes and neurodegenerative disorders. PARP-1 could
      therefore be considered as a potential target for the development of
      pharmacological strategies to enhance the antitumor efficacy of radio- and
      chemotherapy or to treat a number of clinical conditions characterized by
      oxidative or NO-induced stress and consequent PARP-1 activation. Moreover, the
      discovery of novel functions for the multiple members of the PARP family might
      lead in the future to additional clinical indications for PARP inhibitors.

PMID- 11846618
TI  - Protection by nitric oxide of morphine-induced inhibition of rat submandibular
      gland function.
AB  - The effects of morphine, l -arginine (nitric oxide precursor) and l -NAME (nitric
      oxide synthesis inhibitor ) and their concurrent therapy on rat submandibular
      secretory function were studied. Pure submandibular saliva was collected
      intraorally by micro polyethylene cannula from anaesthetized rats using
      pilocarpine as secretagogue. Single intraperitoneal injection of morphine (6 mg
      kg(-1)) to rats induced significant (P< 0.01) inhibition of salivary flow rate
      (28%), total protein (12%) and calcium concentrations (27%). Sodium output was
      increased (23%, P< 0.01). Single intraperitoneal administration of l -arginine
      (100 mg kg(-1)) and l -NAME (10 mg kg(-1)) affected salivary gland function.
      Saliva flow rate was reduced by l -NAME (23%, P< 0.01). The total protein
      concentration of saliva was increased by l -arginine (21%, P< 0.05) and decreased
      by l -NAME (19%, P< 0.01). Calcium concentration of saliva was increased by l 
      arginine (25%, P< 0.01) and reduced by l -NAME (21%, P< 0.01). In combination
      treatment, l -arginine prevented (P< 0.01) morphine-induced reduction of flow
      rate while l -NAME potentiated it (P< 0.01). The secretion of total protein and
      calcium were influenced in a similar trend by concurrent therapy. l -NAME
      potentiated morphine-induced decrease of total protein and calcium concentrations
      (P< 0.01) while l -arginine restored (P< 0.01) them to levels close to control
      and morphine groups respectively. It is concluded that morphine inhibits salivary
      gland function and nitric oxide (NO) plays a positive role in this system. Also
      it is confirmed that morphine inhibitory effects on submandibular function are
      somewhat restored by l -arginine and expanded by l -NAME. The modulatory effect
      of the l -arginine/NO system on salivary gland function is suggested.

PMID- 11846619
TI  - Comparative study of the contractile activity evoked by ATP and diadenosine
      tetraphosphate in isolated rat urinary bladder.
AB  - The present study was designed to investigate the effect and possible
      mechanism(s) of action of ATP and diadenosine tetraphosphate (AP(4)A) on the
      isolated rat urinary bladder rings. ATP ( 0.1- 1 x 10(-3)M) or AP(4)A ( 0.01- 0.1
      x 10(-3)M) produced contractions of the isolated bladder rings in a concentration
      dependent manner. The contraction-induced by AP(4)A in the bladder rings was
      approximately ten times more potent than that produced by ATP. Addition of ATP
      prior to addition of AP(4)A or vice versa desensitized bladder tissue to the
      second agonist with great reduction in the contraction produced. Electrical field
      stimulation (EFS, 40 V, 0.5 ms, 2 Hz) produced contraction (79.8 +/-7.1 g tension
      x g(-1)tissue) in the bladder rings that can be greatly reduced by prior addition
      of ATP or AP(4)A. Theophylline, a P(1)-purinoceptor antagonist, significantly
      reduced the contraction-induced by AP(4)A and did altered that produced by ATP in
      bladder rings. Atropine, a non-selective muscarinic receptor antagonist, or
      indomethacin, a cyclo-oxygenase inhibitor, significantly suppressed the
      contractions of the bladder rings to ATP or AP(4)A. Similarly, nifedipine, an l 
      type Ca(2+)channel blocker, significantly attenuate the contractions induced by
      ATP and AP(4)A in the isolated rat urinary bladder rings. In conclusion, the
      results of the present study show that ATP, AP(4)A, and EFS evoked contractions
      in the rat urinary bladder rings and that the contractions induced by AP(4)A was
      more potent than that produced by ATP. Furthermore, the contractions evoked by
      ATP or AP(4)A were Ca(2+)-dependent and mediated at least in part through one of
      the cyclo-oxygenase products. Also, the present results suggested the involvement
      of the P(1)-purinoceptor in mediating the contractions evoked by AP(4)A but not
      ATP in the bladder rings.

PMID- 11846620
TI  - Effects of lornoxicam, piroxicam, and meloxicam in a model of thermal hindpaw
      hyperalgesia induced by formalin injection in rat tail.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) are frequently used as analgesics.
      Although the results of clinical studies indicate considerable disparity in the
      analgesic efficacy of NSAIDs, the pre-clinical models generally used for the
      study of nociception do not allow a clear distinction to be made between the
      analgesic properties of agents belonging to this family. As clinical pain is
      characterized by hyperalgesia, we evaluated the effects of NSAIDs with similar
      chemical structures but different selectivities for cyclo-oxygenase (COX)-1 and
      COX-2 in a new behavioural model of central hyperalgesia in rats. We assessed the
      effects of lornoxicam, piroxicam, and meloxicam on the reduction of hindpaw
      nociceptive thresholds to thermal stimulation produced by a 10% formaldehyde
      (formalin) injection into rat tail. Each drug was administered intraperitoneally
      (i.p.) at its ED(50)for the anti-inflammatory effect (namely the inhibition of
      carrageenan-induced hindpaw oedema). At this dose (1.3 mg kg(-1), 1.0 mg kg(-1),
      and 5.8 mg kg(-1), respectively), lornoxicam, piroxicam, and meloxicam produced
      the same anti-inflammatory effect, did not modify thermal nociceptive thresholds,
      and significantly reduced the hyperalgesia. However, only lornoxicam was fully
      effective for prevention of hyperalgesia. Our results indicate a dissociation
      between the anti-inflammatory and the anti-hyperalgesic activity of NSAIDs, where
      the latter seems to be more evident after the block of both COX-1 and COX-2.
      Finally, they suggest that our experimental model of thermal hindpaw hyperalgesia
      can be effectively utilized to assess the ability of different drugs to reduce
      central sensitization, and thus hyperalgesia.

PMID- 11846621
TI  - Effects of gender on the pharmacokinetics of drugs secreted by the renal organic
      anions transport systems in the rat.
AB  - The importance of considering sex differences in drug handling studies was
      admitted recently. The present work evaluates the sex influences on the
      pharmacokinetics of para-aminohippuric acid (PAH), the reference substance for
      the renal organic anion transports systems, and furosemide (FS), a standard loop
      diuretic which is also a substrate for this transport system. Female rats
      displayed a lower PAH and FS systemic clearance, and a lower value of the
      elimination rate microconstant from the central compartment for both drugs. These
      results may be explained by the diminution of the renal clearance of both PAH and
      FS observed in females. In summary, sex modifies the pharmacokinetics of organic
      anions. Although additional experimental work must be done to bridge the gap
      between studies using animals and humans, the reported experimental observations
      may have potentially important pharmacological implications. So, caution must be
      exercised in administering drugs like organic anions to females.

PMID- 11846622
TI  - Bayesian estimation of six different sets of carbamazepine pharmacokinetic
      parameters in Egyptian adult epileptic patients.
AB  - The individualization of carbamazepine (CBZ) dosage regimen based on estimation
      of pharmacokinetic (PK) parameters and measurement of serum drug concentration in
      epileptic patients can help to control epilepsy. In a retrospective study, the
      predictive performance of six different sets of CBZ PK parameters selected
      according to the literature was evaluated in 60 adult epileptic patients.
      Patients were administered controlled release CBZ (dose range: 200-1200 mg day(
      1)) as monotherapy and one steady state serum concentration of the drug was
      available for each patient. The Bayesian Program of Abbott (PKS system; Abbott
      Laboratories, Wiesbaden, Germany) was used in the prediction process. Predictive
      measures included estimation of mean prediction error (mpe) for bias, mean
      squared prediction error (mspe) and root mean squared prediction error (rmspe)
      for precision. The analysis showed that three of the investigated six sets
      achieved the best predictive performance in Egyptian patients and consequently,
      the PK parameters of any of these three sets can be used by the Bayesian approach
      as prior information for CBZ dose optimization among the Egyptian adult
      population.

PMID- 11846623
TI  - Chronic infusion of a melanocortin receptor agonist modulates dopamine receptor
      binding in the rat brain.
AB  - Previous studies have shown that melanocortin peptides have facilitatory effects
      on dopaminergic neurotransmission. In the present study we tested the hypothesis
      that chronic exposure to melanocortin receptor agonists causes a prolonged
      release of dopamine resulting in changes in the expression of dopamine receptor
      subtypes. Using an autoradiographic approach we found that a 2 week
      intracerebroventricular infusion of the melanocortin receptor agonist melanotan
      II induced changes in dopamine D(1)-like and D(2)-like receptor binding in
      several regions of the rat brain. D(1)-like receptor binding was increased in the
      nucleus accumbens and the caudate putamen, but reduced in the substantia nigra
      (reticular part), whereas D(2)-like receptor binding was reduced in the caudate
      putamen, but increased in the periaqueductal grey, substantia nigra (compact
      part) and the ventral tegmental area. These data suggest that chronic infusion of
      a melanocortin receptor agonist alters the activity of dopaminergic neurons in
      the ventral tegmental area and substantia nigra, and support the hypothesis that
      melanocortin peptides may regulate the activity of central dopamine neurons.

PMID- 11846624
TI  - Blockade of A(2A) adenosine receptors leads to c-fos inhibition in a rat model of
      brain ischemia.
AB  - Adenosine plays an important role in cerebral ischemia by acting on its own
      receptors, in particular the A(2A)receptor. Its activation leads to excitatory
      amino acid release thus contributing to the ischemic damage. Blockade by specific
      antagonists may protect against cytotoxic injury. Our study was aimed to
      investigate the effect of the blockade of A(2A)receptors, by Sch 58261, on the
      expression of the early gene c-fos, in a model of permanent middle cerebral
      artery occlusion (pMCAo), in rats. In the pMCAo model, ischemia was induced in
      the right hemisphere whereas the contralateral one was considered the control. In
      our study, we have compared pMCAo rats, pMCAo rats treated with Sch 58261 and
      sham operated ones.C-fos was markedly expressed in the ischemic hemispheres,
      whereas lower levels were detected in the contralateral ones of the ischemic
      animals. The lowest bands were observed in sham operated rats. After treatment
      with Sch 58261, a considerable reduction in c-fos expression was observed in the
      ischemic hemispheres, whereas a limited effect was detected in the others. Our
      results suggest that inhibition of immediate-early gene expression by the
      A(2A)receptors antagonist Sch 58261 may contribute to its neuroprotective
      activity.

PMID- 11846625
TI  - Catalase and alpha-tocopherol attenuate blood-brain barrier breakdown in
      pentylenetetrazole-induced epileptic seizures in acute hyperglycaemic rats.
AB  - Experimental data indicate that acute hyperglycaemia can aggravate the
      consequences of epileptic seizures on the permeability of the blood-brain barrier
      (BBB). The purpose of this study was to examine the effects of chronic
      administration of alpha -tocopherol (vitamin E) and acute catalase administration
      on the disrupted BBB during experimentally pentylenetetrazole-induced status
      epilepticus in acute hyperglycaemic rats. The integrity of the BBB was tested
      using the Evans Blue (EB) dye extravasation. The concentration of EB dye was
      measured in four regions of the brain. Epileptic seizures induced a significant
      increase in EB dye extravasation in the brain regions compared with that of the
      groups of rats treated with saline, glucose, catalase and alpha -tocopherol (P<
      0.01). The content of EB dye in the brain regions of animals in the acute
      hyperglycaemia plus epileptic group was higher than that of the saline, glucose,
      catalase, alpha -tocopherol and epileptic groups (P< 0.01). The increased EB dye
      transfer from blood to the brain in status epilepticus and acute hyperglycaemia
      plus status epilepticus was attenuated by the treatment with catalase and alpha 
      tocopherol. These data suggest that a partial reduction in the production of
      reactive oxygen species by catalase and alpha -tocopherol contributes to
      decreases in the content of EB dye across the BBB during pentylenetetrazole
      induced status epilepticus in acute hyperglycaemic rats.

PMID- 11846626
TI  - Effectiveness of oral N -acetylcysteine in a rat experimental model of asthma.
AB  - Oxidative stress appears to be relevant to asthma pathogenesis. Therefore, the
      effectiveness of the antioxidant N -acetylcysteine was examined on antigen
      induced pulmonary responses in sensitized Brown-Norway rats. N -acetylcysteine
      (oral, 1 mmol kg(-1)per day for 7 days before challenge) did not reduce the
      immediate bronchospasm that followed aerosol antigen exposure but prevented
      airway hyperreactivity to 5-hydroxytryptamine at 24 h after antigen challenge,
      and reduced the eosinophils (from 0.178 +/- 0.038 in the absence to 0.064 +/-
      0.020 x10(6)cells ml(-1)in the presence of N -acetylcysteine;P< 0.05), and Evans
      blue dye extravasation in bronchoalveolar lavage fluid. Taurine levels in
      bronchoalveolar lavage fluid from antigen-challenged rats were higher than
      control values but treatment with N -acetylcysteine failed to further increase
      these augmented levels. In conclusion, oral N -acetylcysteine showed beneficial
      effects in an in vivo model of experimental asthma, which confirm and extend the
      previous positive findings obtained in other models of lung injury.

PMID- 11846627
TI  - Imipramine, mianserine and maprotiline block delayed rectifier potassium current
      in ventricular myocytes.
AB  - Imipramine, mianserine and maprotiline are three widely used antidepressant drugs
      with different chemical structure. In the present work we have studied the
      effects of these drugs on the delayed rectifier potassium current (I(K)) in
      myocytes isolated from rat ventricle. The delayed rectifier potassium current,
      responsible for action potential termination, is blocked by all of the three
      drugs I(K)studied in a state-independent manner. Imipramine and mianserine block
      I(K)in a 1 : 1 drug-receptor interaction, whereas maprotiline shows a negative
      cooperativity in the interaction between the channel complex and drug molecules.

PMID- 11846628
TI  - Modulation of inflammatory mediators and PPARgamma and NFkappaB expression by
      pravastatin in response to lipoproteins in human monocytes in vitro.
AB  - Statins are inhibitors of the rate-limiting step of cellular cholesterol
      synthesis. In vitro and in vivo studies suggest that statins have anti
      inflammatory properties independent of their cholesterol-lowering effects. These
      observations prompted us to examine the effects of pravastatin (50 microM) and
      native or oxidized low density lipoprotein (nLDL or oxLDL) (50 microg ml(-1)) on
      primary human monocytes. We found that cells treated with pravastatin prior to
      nLDL and cells pre-treated with oxLDL prior to pravastatin showed increased
      activity of peroxisome proliferator-activated receptor gamma (PPAR gamma).
      Treatment of cells with drug either before incubation with oxLDL or afterwards
      suppressed nuclear factor kappa B (NF kappa B) expression and reduced uptake
      of(125)I-oxLDL by 1.7- and 1.5-fold, respectively. Pravastatin also increased
      PPAR gamma levels and abolished NF kappa B activity in non-stimulated monocytes.
      Statin added to monocytes prior to or after treatment with nLDL or oxLDL
      significantly inhibited generation of matrix metalloproteinases (MMPs), monocyte
      chemotactic protein-1 (MCP-1) and tumor necrosis factor alpha (TNF- alpha). These
      data corroborate previous findings of the pleiotropic role of statins and also
      suggest the involvement of transcription factors such as PPAR gamma and NF kappa
      B in the modulation of the inflammatory processes by statins.

PMID- 11846629
TI  - The effect of nimesulide on the indomethacin- and ethanol-induced gastric ulcer
      in rats.
AB  - In the present study, we investigated the effects of nimesulide, indomethacin,
      naproxene, ibuprofen and diclofenac, at anti-inflammatory doses, on the rat
      gastric tissue (total number = 102). In addition, the effect of nimesulide at
      doses of 100, 300 and 500 mg kg(-1) on indomethacin-induced and ethanol-induced
      damage (ulcer) was examined. The potency of nimesulide was compared with that of
      ranitidine (at 150 mg kg(-1)). Results indicated that nimesulide did not produce
      any gastric damage. Additionally, it has a therapeutic effect on indomethacin-
      and ethanol-induced gastric lesions. Ulcer areas were measured in the rats given
      nonsteroidal anti-inflammatory drugs (NSAIDs). Nimesulide (at doses of 100, 300
      and 500 mg kg(-1)) and ranitidine (at a dose of 150 mg kg(-1)) treated completely
      indomethacin-induced ulcer. The mean ulcer area was 21.9 +/- 8.9 mm(2)in the
      indomethacin-given control group. Nimesulide and ranitidine reduced the ethanol
      induced gastric ulcer. The ulcer area was 114.3 +/- 10.3 mm(2) in the ethanol
      given group and it was 4.5 +/- 4.8, 20.1 +/- 1.66, 15.16 +/- 4.05 mm(2) for
      nimesulide (at doses of 100, 300 and 500 mg kg(-1)), respectively, and 64.16 +/-
      3.97 mm(2) for ranitidine.

PMID- 11846630
TI  - Potential efficacy of a delta 5-aminolevulinic acid thermosetting gel formulation
      for use in photodynamic therapy of lesions of the gastrointestinal tract.
AB  - Photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA)-induced
      protoporphyrin IX may play a role in the treatment of dysplastic Barrett's
      oesophagus. An ALA thermosetting gel Pluronic F-127) was developed and evaluated
      in an in vivo mouse model for potential use in PDT of Barrett's mucosa. In vitro
      studies of the influence of Pluronic F-127 percentage on thermosetting gel
      temperature, followed by the influence of ALA concentration on thermosetting
      temperature and ALA-gel stability as a function of time or temperature were
      studied. In vivo relationships between ALA doses and fluorescence were studied to
      determine the optimal concentration. Fluorescence measurement in vivo showed that
      ALA concentration and time had a nonlinear influence on protoporphyrin IX
      synthesis. For ALA-gel applications longer than 30 min a plateau fluorescence was
      reached, the maximum fluorescence being obtained after 4 h whatever the time of
      contact. The maximum intensity (2824 counts s(-1)) was found with 40 mg mL(-1)
      ALA-gel, and fluorescence intensities differed with time, reaching a maximum
      after 3-4 h. ALA-Pluronic F-127 is a suitable formulation for treatment of
      Barrett's oesophagus, allowing easy application in liquid form at 4 degrees C and
      good adhesion in the oesophagus in gel form, with efficient diffusion of ALA into
      treated mucosa.

PMID- 11846631
TI  - Categorization and nomenclature of vitreous silicate wools.
AB  - There is substantial interest among government agencies in categorizing fibers
      for hazard classification purposes, particularly the commercially important
      synthetic vitreous fibers (e.g., rock wool, slag wool, glass wool, and refractory
      ceramic fibers). The intent of this categorization is to partition the population
      of fibers into distinct categories, which are mutually exclusive, collectively
      exhaustive, easy to understand and implement, and homogeneous with respect to
      potential biological activity. This paper identifies criteria for categorization,
      summarizes historical systems for categorization (e.g., by origin, chemistry and
      structure, physical form and morphology, and application), analyzes the current
      categorization schemes used by the European Community (EC) and the International
      Agency for Research on Cancer (IARC), and proposes an improved partitioning
      method based upon biopersistence/durability. The proposed basis for
      categorization incorporates the best features of the EC and IARC methods,
      eliminates some of their inconsistencies, exploits available knowledge of fiber
      toxicology (much of which was developed in recent years), and is practical to
      implement.

PMID- 11846632
TI  - Joint positive control testing in guinea pig skin sensitization tests. A
      harmonized approach.
AB  - A scheme for the performance of positive control studies within a coordinated
      group of laboratories was proposed (joint positive control testing). The
      procedure has been described, as well as the first results of the validation
      phase of this joint positive control testing project. Adoption of this proposal
      within the participating six laboratories would lead to a reduction in the number
      of guinea pigs required for reliability and sensitivity checks from current
      approximate 12 studies per year down to 2 studies, i.e., 150-300 fewer animals
      per year. Another benefit would be the use of a harmonized, and therefore more
      comparable, method to perform guinea pig tests and interpret the data. In the
      validation phase of joint reading of the positive control studies, the congruency
      of reading could clearly be demonstrated. From the experience gained up to now,
      it was possible to draw the conclusion that a coordinated interlaboratory
      approach for positive control testing was fully acceptable and an improvement
      with regard to animal welfare.

PMID- 11846633
TI  - The use of noncancer endpoints as a basis for establishing a reference
      concentration for formaldehyde.
AB  - Published studies involving formaldehyde were selected for quality and relevance
      for determining whether noncancer endpoints could be used to derive a reference
      concentration for formaldehyde. Chamber studies provided the highest quality data
      for determining the presence of eye, nose, or throat irritation at a known level
      of formaldehyde. Some individuals begin to sense irritation at about 0.5 ppm, 5
      20% report eye irritation at 0.5 to 1 ppm, and greater certainty for sensory
      irritation appears at 1 ppm or greater. These levels of formaldehyde do not
      appear to impact asthmatics even though these individuals are thought to be more
      sensitive to irritants. Mild, reversible changes in pulmonary function (forced
      expiratory volume at 1 s and midexpiratory flow) can occur in sensitized
      individuals at levels approaching 2 ppm. Studies in the manufacturing setting,
      while confounded by multiple exposures, provide useful information for setting
      boundaries for sensory irritation or changes in pulmonary function. Community
      surveys do not provide the specificity nor sensitivity needed to establish a
      reference concentration. Histological studies of the nasal mucosa suffer
      significant methodological and technological shortcomings in addition to issues
      commonly associated with the design of residential and workplace studies. Based
      on the review of chamber, community, and workplace studies of human exposures to
      formaldehyde, it is not possible to identify a specific no observed adverse
      effect level or lowest observed adverse effect level for formaldehyde. Ranges of
      exposures associated with acute sensory irritation can be derived and do include
      sensitive subpopulations. However, given the quality and variability of the data,
      human studies alone, especially those involving sensory irritation, are not
      adequate to serve as a reference concentration for estimating risk, or lack
      thereof, for a lifetime of exposure to formaldehyde. Alternative approaches, such
      as modeling cellular changes observed in animal studies, may be more useful for
      quantitative risk assessment of noncancer endpoints and should be used as an
      adjunct to interpreting human sensory studies.

PMID- 11846634
TI  - Dose response for formaldehyde-induced cytotoxicity in the human respiratory
      tract.
AB  - Human studies of the sensory irritant effects of formaldehyde are complicated by
      the subjective nature of some clinical endpoints. This limits the usefulness of
      such studies for quantitative noncancer risk assessment of airborne formaldehyde.
      Objective measures of the noncancer effects of formaldehyde, such as the rate of
      regenerative cellular proliferation (RCP) secondary to cytolethality, can be
      obtained from laboratory animals but present the challenge of interspecies
      extrapolation of the data. To the extent that uncertainties associated with this
      extrapolation can be reduced, however, dose-response data obtained in laboratory
      animals are a viable alternative to clinical studies. Here, we describe the
      extrapolation of dose-response data for RCP from F344 rats to humans. Rats
      inhaled formaldehyde (0, 0.7, 2.0, 6.0, 10, and 15 ppm) 6 h/day, 5 days/week for
      up to 2 years. The dose response for RCP was J-shaped, with the rates of RCP at
      0.7 and 2.0 ppm below but not statistically different from control, while the
      rates at the higher concentrations were significantly greater than control. Both
      the raw J-shaped data and a hockey-stick-shaped curve fitted to the raw data were
      used for predicting the human dose response for RCP. Cells lining the nasal
      airways of F344 rats and rhesus monkeys are comparably sensitive to the
      cytolethal effects of inhaled formaldehyde, suggesting that the equivalent human
      cells are also likely to be comparably sensitive. Using this assumption, the
      challenge of rat-to-human extrapolation was reduced to accurate prediction of
      site-specific flux of formaldehyde from inhaled air into the tissue lining the
      human respiratory tract. A computational fluid dynamics model of air flow and gas
      transport in the human nasal airways was linked to a typical path model of the
      human lung to provide site-specific flux predictions throughout the respiratory
      tract. Since breathing rate affects formaldehyde dosimetry, cytotoxicity dose
      response curves were predicted for three standard working levels. With the most
      vigorous working level, the lowest concentrations of formaldehyde predicted to
      exert any cytotoxic effects in humans were 1.0 and 0.6 ppm, for the J-shaped and
      hockey-stick-shaped RCP curves, respectively. The predicted levels of response at
      the lowest effect concentrations are smaller than can be measured clinically.
      Published literature showing that the cytotoxicity of inhaled formaldehyde is
      related to exposure level rather than to duration of exposure suggests that the
      present analysis is a reasonable basis for derivation of standards for continuous
      human exposure.

PMID- 11846635
TI  - Evaluation of the carcinogenicity of 1,1-dichloroethylene (vinylidene chloride).
AB  - The U.S. Environmental Protection Agency has classified 1,1-dichloroethylene
      (vinylidene chloride; VDC) as a "C" carcinogen and has developed an inhalation
      unit risk value and an oral cancer slope factor for this chemical. The
      development and use of these cancer potency estimates for risk assessment
      purposes are questionable. The inhalation unit risk value is based on increased
      kidney adenocarcinomas in Swiss mice from one study. This type of cancer was not
      increased in female mice or in rats or hamsters in the same study nor in male
      mice of a similar strain in another study with higher VDC exposures. The VDC oral
      cancer slope factor is based on a non-statistically significant increase in
      adrenal pheochromocytomas in male rats following oral exposure in a standard
      National Toxicology Program chronic bioassay. Both human and animal literature
      relevant to VDC carcinogenicity was reviewed according to the USEPA draft
      Guidelines for Carcinogen Risk Assessment with the objective of determining the
      weight-of-evidence for VDC carcinogenicity. We conclude that information
      currently available for VDC is most appropriately characterized in a weight-of
      evidence narrative by the descriptor "inadequate for an assessment of human
      carcinogenic potential." For chemicals with this descriptor, dose-response
      assessment is not indicated. Under this guidance, quantitative estimates of
      cancer risks associated with VDC exposure are inappropriate until additional,
      more definitive evidence for human carcinogenicity becomes available.

PMID- 11846636
TI  - Preclinical safety evaluation of recombinant human interleukin-10.
AB  - Escherichia coli-derived recombinant human interleukin-10 (rhuIL-10) has been
      evaluated in an extensive series of in vivo and in vitro nonclinical safety
      studies, including genetic toxicology, single- and repeat-dose systemic toxicity
      and toxicokinetics, reproductive toxicity, and specialized irritation studies.
      The primary test species in the toxicology studies were the mouse and monkey
      based on rhuIL-10 activity in receptor binding and ex vivo cytokine assays.
      Supported by a detailed preclinical program of therapeutic and prophylactic
      animal models in autoimmune diseases, the initial clinical development program
      has focused on investigating the therapeutic potential of rhuIL-10 (Tenovil) in
      Crohn's disease and rheumatoid arthritis. The results of the subcutaneous
      toxicity studies, up to 3 months dosing duration in mice and 6 months dosing
      duration in monkeys, support the development of rhuIL-10 for present and future
      clinical indications by the subcutaneous route of administration.

PMID- 11846637
TI  - Testing extrapolation of a biologically based exposure-response model from in
      vitro to in vivo conditions.
AB  - Models of carcinogenesis may become so flexible as to preclude the possibility of
      being falsified by data. This problem is removed in part by stronger biophysical
      specification of processes and parameters within the model prior to fitting to in
      vivo data on the relationship between exposure and cancer incidence. This paper
      explores the use of a biophysical model of chromosomal damage, cellular
      transformation, repair, mitosis, initiation, promotion, progression, and
      cytotoxicity in developing exposure-response models for radiation-induced cancer.
      Many of the aspects of model form and parameter values are developed from in
      vitro data, and the model then is extrapolated to the in vivo setting using a
      dosimetric model to account for dose inhomogeneity within the lung tissue of rats
      exposed to radon progeny in air. The ability of the model to predict cancer
      incidence in the rats is assessed and is shown to be problematic at higher doses.
      This calls into question whether a full claim may be made about the ability of
      first-principle models to fully constrain models applied to in vivo data at
      present. Possible explanations for the discrepancy, and implications for
      extrapolation, are provided.

PMID- 11846638
TI  - The use of mechanistic data and the handling of scientific uncertainty in
      carcinogen risk assessments. The trichloroethylene example.
AB  - The purpose of this paper is to explore how risk assessors actually use
      mechanistic data in carcinogen risk assessment and to discuss how the handling of
      scientific uncertainty may affect the outcome of the risk assessment. The
      analysis is performed by comparing 29 trichloroethylene risk assessment documents
      in general and 2 of these, namely the ECETOC (1994, Trichloroethylene: Assessment
      of Human Carcinogenic Hazard, Technical Report No. 60) and the OECD/EU (1996,
      Initial Assessment Report for the 4th SIAM (Screening Information Data Set
      Initial Assessment Meeting), May 1996: Trichloroethylene, sponsor country, United
      Kingdom [Draft]), in more detail. It is concluded that in this example the ECETOC
      required less evidence for considering a carcinogenic mechanism irrelevant to
      humans than did the OECD/EU risk assessors. There are examples of when two risk
      assessors have selected different primary data for their argumentation and also
      examples of how one and the same primary publication was interpreted differently.
      Biased data selection and evaluation of primary data that correlate to the risk
      assessor's overall conclusions have also been identified. The general comparison
      of all 29 TCE risk assessment documents indicates that the assessment of
      scientific uncertainty in the mechanistic data affects the overall conclusions.

PMID- 11846639
TI  - Risk analysis for mortality from respiratory tumors in a cohort of refractory
      ceramic fiber workers.
AB  - Although workers in refractory ceramic fibers (RCF) manufacturing facilities have
      experienced no elevations in lung cancer or mesothelioma rates, the historical
      experience of asbestos together with animal studies of RCF have led to ongoing
      studies of the respiratory health of RCF workers. We have compared lung cancer
      and mesothelioma in the accumulated mortality experience of a cohort of male RCF
      production workers (Lemasters et al., 2001, submitted for publication) to that
      which would have been expected if RCF had a carcinogenic potency similar to that
      of various forms of asbestos. To accomplish this, we used risk models recently
      formalized by Hodgson and Darnton (2000, Ann. Occup. Hyg. 41, 13-36) for asbestos
      cohorts together with the RCF exposure measurements and historical
      reconstructions of Rice and colleagues (1997, Appl. Occup. Environ. Hyg. 12, 54
      61). Deaths from lung cancer in the RCF cohort are statistically significantly
      below that which would be expected if RCF had the potency of either crocidolite
      or amosite. The mortality is also lower than would be expected if RCF had the
      potency of chrysotile, but the difference is not statistically significant. For
      mesothelioma, the anticipated numbers of deaths under hypotheses of asbestos-like
      potency are too small to be rejected by the zero cases seen in the RCF cohorts.
      The current epidemiologic studies do not rule out risk, but they clearly do rule
      out lung cancer risks like those of crocidolite or amosite. The residual
      uncertainty justifies ongoing workplace surveillance.

PMID- 11846640
TI  - Appraisal of risks from nonoccupational exposure to chlorpyrifos.
AB  - The toxicological database for chlorpyrifos indicates that humans are not more
      sensitive than laboratory animals to the toxic effects. Although an oral dose of
      1 mg/kg-day resulted in measurable levels of chlorpyrifos in the blood, daily
      dosing at this level from 9 days to 2 years did not affect brain
      acetylcholinesterase activity (AChE) in laboratory animals. Developmental
      toxicity did not occur at doses below maternal toxicity. Most nonoccupational
      illnesses resulting from entry into areas treated with chlorpyrifos likely stem
      from odor, rather than the ability of the organophosphate to inhibit AChE. Based
      on biological monitoring studies, chronic aggregate nonoccupational exposures to
      chlorpyrifos ranged from 0.0002 mg/kg-day (adults) to 0.0005 mg/kg-day (infants
      and small children)-1 order of magnitude less than exposures estimated by
      standard procedures. Other biological monitoring data indicated that cumulative
      exposure to all organophosphate pesticides ranged from 0.0003 mg/kg-day (adults)
      to 0.003 mg/kg-day (children). Considering all these factors, the risks of
      aggregate, nonoccupational exposure to chlorpyrifos have been overstated by more
      than a 1000-fold.

PMID- 11846641
TI  - The in vivo rodent test systems for assessment of carcinogenic potential.
AB  - A Drug Information Association (DIA) workshop was held in May 2001 to discuss the
      outcome of the International Life Sciences Institute-Health and Environmental
      Sciences Institute (ILSI-HESI) project on alternative models for carcinogenicity
      assessment such as the P53(+/-) and XPA(+/-) knockout mouse models, the RasH2 and
      Tg.AC transgenic mouse models, and the neonatal mouse model. The "ICH Guideline
      S1B on Testing for Carcinogenicity of Pharmaceuticals" advocates that
      carcinogenicity testing of pharmaceuticals, when needed, might be carried out
      choosing one 2-year rodent carcinogenicity study (rat) plus one other study that
      supplements the 2-year study and providing additional information that is not
      readily available from the 2-year study: either (1) a short- or medium-term in
      vivo rodent test system or (2) a 2-year carcinogenicity study in a second rodent
      species (mouse). Another topic of discussion was pros and cons of the short- and
      medium-term models being evaluated by the ILSI-HESI project, in particular the
      usefulness of the models in relation to results of genotoxicity assays. Further
      discussions were advised following publication of the ILSI-HESI database, which
      is expected before the end of 2001. The use of the short- and medium-term rodent
      test systems were not considered appropriate for the assessment of carcinogenic
      potential of biotechnology-derived medicinal products.

PMID- 11846642
TI  - Investigations of benzene exposure, benzene poisoning, and malignancies in China.

PMID- 11846643
TI  - Highly stereoselective syntheses of syn- and anti-1,2-amino alcohols.
AB  - The reduction of N-protected amino ketones can be carried stereoselectively to
      produce either the syn- or anti-amino alcohol diastereomer. Carbamate-protected
      amino ketones can be reduced predictably and selectively to anti-amino alcohols
      with LiAlH(O-t-Bu)3 in ethanol at -78 degrees C. N-Trityl-protected amino ketones
      can be reduced selectively to syn-amino alcohols with LiAlH(O-t-Bu)3 in THF at -5
      degrees C.

PMID- 11846644
TI  - Intrinsic (gas phase) thermodynamic stability of 2-adamantyl cation. Its bearing
      on the solvolysis rates of 2-adamantyl derivatives.
AB  - The standard enthalpy of formation of gaseous 2-adamantyl chloride(2-Ad-Cl) was
      determined by calorimetric techniques. The standard Gibbs energy change for the
      chloride anion exchange between 1-adamantyl (1-Ad+) and 2-adamantyl (2-Ad+)
      cations in the gas phase was obtained by Fourier transform ion cyclotron
      resonance spectroscopy (FT ICR). Theoretical calculations at the G2(MP2) level
      were performed on these and other relevant species. This and data from the
      literature provided three highly consistent independent estimates of the relative
      stabilities of 2-Ad+ and 1-Ad+. This difference in gas-phase stability was
      compared to the differential structural effects on the rates of solvolysis of the
      corresponding chlorides and tosylates, and it was shown that the thermodynamic
      stability of the secondary cation is the leading factor determining the
      solvolytic reactivity of the precursors in the absence of solvent effects. Thus,
      under these conditions, the previously established linear free energy correlation
      between carbenium ion stability and solvolytic reactivity of bridgehead
      derivatives applies also to secondary derivatives.

PMID- 11846645
TI  - Asymmetric intramolecular [2 + 2] photocycloadditions: alpha- and beta-hydroxy
      acids as chiral tether groups.
AB  - Chiral alpha- and beta-hydroxy acids such as (S)-lactic acid, (S)-phenyllactic
      acid, (S)-mandelic acid, or (3R)-3-hydroxybutyric acid have been used as tether
      groups for intramolecular and diastereoselective [2 + 2] photocycloaddition of 3
      oxocyclohexene carboxylic acid derivatives. Total regiocontrol toward the
      straight adduct and high diastereoselectivities (up to 94%) were observed in the
      case of butenyl lactate 11. After separation of the two diastereoisomers,
      cleavage of the chiral tether under basic conditions afforded cyclobutane
      lactones in good yield and enantiomeric pure form. An X-ray structure has been
      recorded that confirmed the relative and absolute configuration of the three
      contiguous stereogenic centers assigned according to CD spectra.

PMID- 11846646
TI  - Selective mono-C-methylations of arylacetonitriles and arylacetates with
      dimethylcarbonate: a mechanistic investigation.
AB  - The very high mono-C-methylation selectivity (>99%) of arylacetic acid
      derivatives (ArCH2X; X = CN, CO2Me) with dimethyl carbonate (DMC) is due to a
      mechanism that involves consecutive methoxycarbonylation, methylation, and
      demethoxycarbonylation steps. Important aspects of this mechanism are clarified
      herein by a kinetic investigation. In the case of arylacetonitriles, at 140
      degrees C, the comparison of the rate constants of model reactions involving 2
      phenyl propionitrile, phenylacetonitrile, 2-methoxycarbonylphenylacetonitrile,
      and 2-methyl-2-methoxy carbonylphenyl acetonitrile (compounds 1a-4a,
      respectively) with DMC indicates that the methylation process is the fastest and
      the irreversible step, which drives the overall reaction to completion. The
      situation is reversed for arylacetic esters, where the methylation is more
      difficult than the demethoxycarbonylation reaction; therefore, a higher reaction
      temperature is required.

PMID- 11846647
TI  - A new 3-(phenylseleno)allylic cation: its regioselective C-C bond formation
      reaction with nucleophiles.
AB  - Highly useful C-C bond formation using 2-ethoxy-3-(phenylseleno)prop-2-enal
      acetal 2 was examined with various Lewis acids. The reaction of 2 with the silyl
      enol ether in the presence of BF(3)*Et2O, ZnBr2, or SnBr4 regioselectively
      provided (Z)-3,4-diethoxy-5-(phenylseleno)pent-4-enophenone 5a in high yields. On
      the other hand, the reaction with other Lewis acids such as EtAlCl2 or SnCl4 gave
      5-(phenylseleno)- 6 or non-selenopentane-1,4-dione 7, respectively. Novel prop-2
      enal acetals 2-4 and 13-15 reacted with various nucleophiles to give pent-4
      enophenones 5a,b, 10a, 12, and 16-18, S-ethyl pent-4-enoate 5b, alkylated vinylic
      sulfide 10b, 3-pentenenitrile 5d, and 10c. A versatile pent-4-enophenone 5a could
      be converted to tetrahydrofuran 20 and penta-2,4-dienophenone 19, the Diels-Alder
      reactions of which with dienophiles gave the adducts 24 and 25.

PMID- 11846648
TI  - Linear ketenimines. Variable structures of C,C-dicyanoketenimines and C,C-bis
      sulfonylketenimines.
AB  - C,C-dicyanoketenimines 10a-c were generated by flash vacuum thermolysis of ketene
      N,S-acetals 9a-c or by thermal or photochemical decomposition of alpha-azido-beta
      cyanocinnamonitrile 11. In the latter reaction, 3,3-dicyano-2-phenyl-1-azirine 12
      is also formed. IR spectroscopy of the keteniminines isolated in Ar matrixes or
      as neat films, NMR spectroscopy of 10c, and theoretical calculations (B3LYP/6
      31G) demonstrate that these ketenimines have variable geometry, being essentially
      linear along the CCN-R framework in polar media (neat films and solution), but in
      the gas phase or Ar matrix they are bent, as is usual for ketenimines.
      Experiments and calculations agree that a single CN substituent as in 13 is not
      enough to enforce linearity, and sulfonyl groups are less effective that cyano
      groups in causing linearity. C,C-bis(methylsulfonyl)ketenimines 4-5 and a C-cyano
      C-(methylsulfonyl)ketenimine 15 are not linear. The compound p
      O2NC6H4N=C=C(COOMe)2 previously reported in the literature is probably somewhat
      linearized along the CCNR moiety. A computational survey (B3LYP/6-31G) of the
      inversion barrier at nitrogen indicates that electronegative C-substituents
      dramatically lower the barrier; this is also true of N-acyl substituents.
      Increasing polarity causes lower barriers. Although N
      alkylbis(methylsulfonyl)ketenimines are not calculated to be linear, the barriers
      are so low that crystal lattice forces can induce planarity in N
      methylbis(methylsulfonyl)ketenimine 3.

PMID- 11846650
TI  - Synthesis of 2-oxazolone-4-carboxylates from 3-nosyloxy- and 3-bromo-2
      ketoesters.
AB  - New methods for the synthesis of 2-oxazolone-4-carboxylates from 3-nosyloxy- and
      3-bromo-2-ketoesters are described. Condensation of 3-nosyloxy-2-ketoesters with
      methyl carbamate in refluxing toluene in the presence of p-TSA provided 2
      oxazolone-4-carboxylates in good yields (41-80%). Alternatively, bromination of
      alpha-ketoesters with CuBr2 provided 3-bromo-2-ketoesters which condensed with
      methyl carbamate in the presence of p-TSA and AgOTf under similar conditions to
      provide 2-oxazolone-4-carboxylates in comparable yields (30-79%). The 2-oxazolone
      4-carboxylates bear functionality that can be elaborated to a variety of
      potentially useful compounds. For example, some of these heterocycles were
      readily N-acylated, reduced to alcohols, or saponified and coupled with amino
      acids.

PMID- 11846649
TI  - Stereocontrolled preparation of a nonpeptidal (-)-spirobicyclic NK-1 receptor
      antagonist.
AB  - The synthesis of a spirobicyclic NK-1 receptor (Substance-P) antagonist 1
      antipode is described. Retrosynthetic analysis reveals an allylic halide A
      bearing the cyclopropoxy-substituted aryl group and a 2-phenyl-3-piperidone B.
      The stereochemistry in the spirobicyclic system bearing three chiral centers is
      initially set via a highly diastereoselective zinc-mediated coupling of the
      allylic bromide 23 to the optically active ketopiperidine 3. The remaining
      benzylic asymmetric center is set by a diastereoselective hydroboration followed
      by cyclization to the spirobicyclic system.

PMID- 11846651
TI  - Heteroatom influence on the pi-facial selectivity of Diels-Alder cycloadditions
      to 1-oxa-4-thia-6-vinylspiro[4.5]dec-6-ene, 3-methoxy-3-methyl-2
      vinylcyclohexene, and 3-methoxy-2-vinylcyclohexene.
AB  - The facial selectivities of the Diels-Alder cycloadditions of several dienophiles
      to the title substrates were studied. The observed selectivities are interpreted
      as a consequence of the relative steric interactions offered by the substituents.
      The addition of dimethylacetylene dicarboxylate (DMAD) is influenced by the
      electrostatic repulsion arising from the interaction of an electron pair orbital
      on the acetal oxygen and the orthogonal pi-orbital of the acetylene unit in DMAD
      in the syn-to-oxygen addition of the latter. This repulsion is offset on
      coordination of Li+ to the said oxygen electron pair orbital, and the addition
      thus proceeds syn to oxygen. The enhanced and accelerated syn-to-oxygen addition
      in lithium perchlorate in nitromethane is interpreted as a consequence of the
      coordination of Li+ to both the acetal oxygen and a heteroatom in the dienophile
      that brings them in close proximity to facilitate a reaction. The Li+-oxygen
      combination, however, also exerts some steric effect that results in reduced syn
      to-oxygen addition of dienophiles having large substituents such as N
      phenylmaleimide.

PMID- 11846652
TI  - Structure-reactivity correlation of anilines in acetic acid.
AB  - The oxidation of aniline in glacial acetic acid with percarbonate, a dry carrier
      of hydrogen peroxide, is a second-order reaction conforming to the isokinetic
      relationship. The hitherto followed method of correlation of the reaction rates
      in terms of the structure-reactivity relationships is unsatisfactory and
      erroneous. But the reaction rates of molecular anilines, obtained for the first
      time, conform to the structure-reactivity relationships.

PMID- 11846654
TI  - Functionalized macrocyclic ligands for use in supramolecular chemistry.
AB  - The synthesis of three cross-conjugated macrocycles bearing pyridine
      functionality is described. The ability of two of these molecules, 5a and 5c, to
      behave as 4,4'-bipyridine mimics in self-assembly reactions is demonstrated by
      axial coordination to a metalloporphyrin. The directed coordinative ability of
      the pyridine rings ensures predictable self-assembly into well-ordered nanoscale
      systems, both in solution and the solid state. 1H, 13C, and HMQC NMR
      spectroscopic experiments and ESI MS have been used to characterize the
      supramolecular complexes in solution. X-ray crystallographic analysis of solid
      state assemblies 7a and 7c provides insight into the scope and flexibility of
      these macrocyclic ligands as supramolecular building blocks. UV-vis and
      fluorescence spectroscopies provide a description of their electronic
      characteristics.

PMID- 11846653
TI  - Reactions of hydro(pero)xy derivatives of polyunsaturated fatty acids/esters with
      nitrite ions under acidic conditions. Unusual nitrosative breakdown of methyl 13
      hydro(pero)xyoctadeca-9,11-dienoate to a novel 4-nitro-2-oximinoalk-3-enal
      product.
AB  - 13(S)-hydroperoxy- and 13(S)-hydroxyoctadeca-9,11-dienoic acids (1a/b), 15(S)
      hydroperoxy- and 15(S)-hydroxyeicosa-5,8,11,13-tetraenoic acids (2a/b), and their
      methyl esters reacted smoothly with NO2- in phosphate buffer at pH 3-5.5 and at
      37 degrees C to afford mixtures of products. 1b methyl ester gave mainly the 9
      nitro derivative 3b methyl ester (11% yield) and a peculiar breakdown product
      identified as the novel 4-nitro-2-oximinoalk-3-enal derivative 4 methyl ester
      (15% yield). By GC-MS hexanal was also detected among the products. Structures 3b
      and 4 methyl esters were secured by 15N NMR analysis of the products prepared
      from 1b methyl ester upon reaction with Na15NO2. 4 methyl ester (14% yield) was
      also obtained from 1a methyl ester along with the nitrated hydroperoxy derivative
      3a methyl ester (10% yield). Under the same conditions, 2a/b methyl esters gave
      mainly the corresponding nitrated derivatives 5a/b, with no detectable breakdown
      products, whereas the model compound (E,E)-2,4-hexadienol (6) afforded two main
      nitrated derivatives identified as 7 and 8. A reaction pathway for 1a/b methyl
      esters was proposed involving conversion of nitronitrosooxyhydro(pero)xy
      intermediates which would partition between two competing routes, viz., loss of
      HNO2, to give 3a/b methyl esters, and a remarkably facile fission leading to 4
      methyl ester and hexanal.

PMID- 11846655
TI  - Molecular engineering of C60-based conjugated oligomer ensembles: modulating the
      competition between photoinduced energy and electron transfer processes.
AB  - A series of novel and soluble C60-(pi-conjugated oligomer) dyads were
      synthesized, starting from suitably functionalized oligomer precursors (i.e.,
      dihexyloxynaphthalene, dihexyloxynaphthalene-thiophene, and dihexyloxybenzene
      thiophene). A systematic change in the nature of the oligomeric component allowed
      (i) tailoring the light absorption of the chromophore by shifting the ground
      state absorption from the ultraviolet to the visible region and (ii) varying the
      oxidation potential of the donor. The resulting electro- and photoactive dyads
      were examined by electrochemical and photophysical means. In general, both
      singlet-singlet energy transfer and intramolecular electron transfer were found
      to take place and, most importantly, to compete with each other in the overall
      deactivation of the photoexcited oligomer. The selection of polar solvents in
      combination with the dihexyloxybenzene-thiophene donor shifted the reactivity
      from an all energy (1a; dihexyloxynaphthalene) to an all electron-transfer
      scenario (1d, dihexyloxybenzene-thiophene). Encouraged by the favorable electron
      transfer properties of dyad 1d, we prepared photodiodes by embedding 1d between
      asymmetric metal contacts, which showed external monochromatic efficiencies
      (IPCE) close to 10% at the maximum absorption of the molecule.

PMID- 11846656
TI  - Palladium(0)-catalyzed enantioselective O,S-rearrangement of racemic O-allylic
      thiocarbamates: a new entry to enantioenriched allylic sulfur compounds.
AB  - Reaction of (+/-)-(E)-pent-3-en-2-ol, (+/-)-(E)-hept-4-en-3-ol, (+/-)-(E)-2,6
      dimethylhept-4-en-3-ol, (+/-)-cyclohex-2-en-1-ol, and (+/-)-cyclohept-2-en-1-ol
      with methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, and benzyl
      isothiocyanate gave the corresponding racemic O-allylic thiocarbamates of medium
      to good thermal stability in good yields. The palladium(0)-catalyzed
      rearrangement of the (+/-)-(E)-pent-3-en-2-ol-, (+/-)-(E)-hept-4-en-3-ol-, (+/-)
      cyclohex-2-en-1-ol-, and (+/-)-cyclohept-2-en-1-ol-derived O-allylic
      thiocarbamates at room temperature in methylene chloride by using Pd2(dba)3*CHCl3
      (dba = dibenzylideneacetone) as precatalyst and (+)-(1R,2R)-1,2-bis-N-((2
      (diphenylphosphino)benzoyl)-1,2-diaminocyclohexane as ligand for the palladium
      atom proceeded quantitatively and gave the corresponding acyclic (R)-configured S
      allylic thiocarbamates and the cyclic (S)-configured S-allylic thiocarbamates
      with ee values ranging from 85% to > or = 99% in yields of 76-94%. Rearrangement
      of the O-allylic thiocarbamates carrying a methyl group at the N atom not only
      was the fastest but also proceeded with the highest enantioselectivity. No
      rearrangement was observed under these conditions in the case of the racemic N
      methyl O-allylic thiocarbamate derived from (+/-)-2,6-dimethylhept-4-en-3-ol,
      which has a branched carbon skeleton. (S)-cyclohex-2-enethiol of 97% ee was
      obtained through hydrolysis of the corresponding N-methyl S-allylic
      thiocarbamate. 2-((R)-(E)-1-methylbut-2-enylsulfanyl)pyrimidine of 91% ee and 2
      ((S)-cyclohex-2-enylsulfanyl)pyrimidine of 97% ee were synthesized in one
      synthetic operation from the corresponding N-methyl S-allylic thiocarbamates and
      2-chloropyrimidine. Similarly, (S)-cyclohex-2-enylsulfanyl)benzene of 97% ee was
      obtained in one synthetic operation from the corresponding N-methyl S-allylic
      thiocarbamate through a palladium(0)-catalyzed substitution of iodobenzene in the
      presence of a base. The palladium(0)-catalyzed enantioselective rearrangement of
      O-allylic carbamates to S-allylic carbamates has been extended from the solution
      phase to the solid phase by using a methyl thioisocyanate polystyrene resin. In
      the case investigated the enantioselectivity of the rearrangement on the solid
      phase was considerably lower than that in solution.

PMID- 11846657
TI  - Flash photolysis of (E)-1,2-bis(1-chloro-1-phenylmethyl)cyclopropane. Generation
      of 1,5-diphenylpentadienyl radical and 1,5-diphenylpentadienylium cation.
AB  - The 1,5-diphenylpentadienyl radical (5) is generated from (E)-1,2-bis(1-chloro-1
      phenylmethyl)cyclopropane (1) via a two-photon process, either in cyclohexane or
      in acetonitrile as solvent. Two-laser two-color flash photolysis experiments show
      that excitation of the benzylic radical generated by homolysis of the first C-Cl
      bond leads, after ring-opening and proton loss, to the stabilized radical 5. This
      radical is also generated by photolysis of either (1E,3E)-5-chloro-1,5-diphenyl
      1,3-pentadiene (6) or (1E,4E)-1,5-diphenyl-1,4-)pentadiene (7) via one-photon or
      two-photon processes, respectively. On the other hand, laser flash photolysis of
      1 in acetonitrile also produces some 1,5-diphenylpentadienylium cation (10)
      generated via a one-photon process. Its formation can be explained as due to
      competitive photoheterolysis leading to a benzylic cation which thermally ring
      opens and dehydrohalogenates. Species 10 is more efficiently generated by
      photolysis of 6 in acetonitrile and undergoes photoisomerization after laser
      excitation.

PMID- 11846658
TI  - Regioselective palladium-catalyzed alkylation of allylic halides with benzylic
      grignard reagents. Two-step synthesis of abietane terpenes and tetracyclic
      polyprenoid compounds.
AB  - A highly regioselective palladium-catalyzed alpha-alkylation of allylic bromides
      1a,c-e and chloride 1b with substituted and unsubstituted benzylic Grignard
      reagents is reported. The resulting all-trans polyenehomobenzene derivatives were
      obtained in excellent yields and regioselectivity. These products were easily
      converted to abietane-type diterpenes (10-12) and tetracyclic polyprenoid
      compounds (13, 14) through a Lewis acid-promoted cascade polyene cyclization
      reaction.

PMID- 11846659
TI  - Synthesis of mono- and difluoronaphthoic acids.
AB  - Aryl carboxamides are useful structural units found in several biologically
      active compounds. Unlike their benzoic acid counterparts, fluorinated versions of
      naphthoic acids are relatively unknown. In connection with a recent project, we
      needed viable syntheses of several mono- and difluorinated naphthoic acids.
      Herein we describe the synthesis of 5-, 6-, 7-, and 8-fluoro-1
      naphthalenecarboxylic acids and 5,7-, 5,8-, 6,7-, and 4,5-difluoro-1
      naphthalenecarboxylic acids. The 5-fluoro derivative 1was obtained from the
      corresponding 5-bromo compound via electrophilic fluorination of the lithio
      intermediate. The rest of the monofluoro (2, 3, and 4) and the difluoro acids (5,
      6, and 7) were prepared by a new, general route which entailed the elaboration of
      commercial fluorinated phenylacetic acids to 2-(fluoroaryl)glutaric acids with
      differential ester groups; selective hydrolysis to a mono acid, intramolecular
      Friedel-Crafts cyclization, and aromatization furnished the target structures. An
      alternative process to assemble a naphthalene skeleton is also presented for the
      difluoro acids 5 and 6. Finally, 4,5-difluoro-1-naphthalenecarboxylic acid (8)
      was prepared expeditiously from 1,8-diaminonaphthalene by adapting classical
      reactions.

PMID- 11846660
TI  - Synthesis and interaction with copper(II) cations of cyano- and
      aminoresorcin[4]arenes.
AB  - Following our studies on resorcin[4]arenes, we synthesized new macrocycles
      containing cyanomethyl and aminomethyl side chains. Three stereoisomers (2a-c) of
      the former were obtained by BF3*Et2O tetramerization of the corresponding trans
      cinnamic acid derivative and were shown to be in the 1,2-alternate, cone, and 1,3
      alternate conformations. Conversely, the tetraamino derivative 6a in the cone
      conformation was prepared from the corresponding tetrabromide 3a. The
      interactions with Cu(II) cations of the new compounds were analyzed by
      measurements of 1H NMR and EPR spectra in parallel with molecular modeling
      calculations.

PMID- 11846661
TI  - Inhibitors of plasmin that extend into both the S and S' binding sites:
      cooperative interactions between S1 and S2.
AB  - A new procedure for the synthesis of cyclohexanone-based inhibitors of serine
      proteases is reported. In this procedure the reactive ketone functionality is
      carried through the synthesis in masked form as a TBDMS-protected alcohol.
      Deprotection followed by oxidation of the alcohol generates the final form of the
      inhibitor. Two new inhibitors, which interact with the S1-S3 and S2' subsites of
      plasmin, are synthesized using this procedure. Inhibitors 1 and 2 have IC50
      values against plasmin of 20 and 24 microM, respectively. The inhibition studies
      show that cooperative binding of inhibitors in the S1 and S2 subsites of plasmin
      is important for determining inhibitor selectivity.

PMID- 11846662
TI  - A tin hydride designed to facilitate removal of tin species from products of
      stannane-mediated radical reactions.
AB  - The stannane 1, which is simple to prepare, behaves like the conventional
      reagents Bu3SnH and Ph3SnH in standard free radical reactions, but with the
      special characteristic that the tin-containing byproducts are easily and very
      largely removed by mild hydrolysis (LiOH-water-THF or TsOH-water-THF), which
      converts them into base-soluble (aqueous NaHCO3) materials. The performance of
      stannane 1 was evaluated for a range of radical reactions involving halides,
      selenides, Barton-McCombie deoxygenation, and enyne cyclization. In several cases
      the effectiveness of the workup procedure in removing tin species was monitored
      by 1H NMR.

PMID- 11846664
TI  - De-aromatizing phosphole.
AB  - Quantum-chemical DFT calculations using the B3LYP functionals have been carried
      out for 1-R-substitued phospholes and some 1-R-substitued 3,4-dimethylphospholes
      where R = H, Me, Ph, CN, OH, OMe, F, Cl, and Br. The aromaticity of the
      phospholyl rings is interpreted as a function of geometric, magnetic, and
      energetic indexes. It is shown, in agreement with previous experimental results,
      that phosphole aromaticity does not correlate with pyramidality at phosphorus.
      Variation of hyperconjugative and, to a lesser extent, conjugative effects is
      responsible for the change in cyclic delocalization for the phospholes studied
      here.

PMID- 11846663
TI  - Application of the palladium-catalyzed borylation/Suzuki coupling (BSC) reaction
      to the synthesis of biologically active biaryl lactams.
AB  - The palladium-catalyzed, two-step, one-pot borylation/Suzuki coupling (BSC)
      reaction was developed to synthesize sterically hindered 2,2'-disubstituted
      biphenyl and phenyl-indole compounds in a short, simple, and efficient manner
      from two easily accessible aryl halides. High yields can be obtained by choosing
      properly both components according to their rough electronic properties. The
      illustration of the utility of this method was provided by the solution and solid
      phase synthesis of seven- or eight-membered biphenyl lactams 5a-e, as well as
      paullone 3a. These compounds exhibit moderate albeit significant cytotoxicities
      and may serve as structural models for future medicinal chemistry developments.

PMID- 11846666
TI  - Inversion vs retention of configuration in gas-phase ammonium ion/alcohol
      reactions.
AB  - The potential energy surface for gas-phase reactions of ammonium ion with
      alcohols was examined by ab initio and DFT methods. Transition structures for
      inversion (S(N)2) and retention (S(N)F) mechanisms were located for 2-propanol
      and exo-2-norbornanol. The S(N)F (retention) process was found to be 6-8 kcal/mol
      higher in energy than the inversion S(N)2 counterpart for the 2-propanol system.
      The retention process in the 2-exo-norbornanol/ammonium ion system was favored by
      1.3 kcal/mol.

PMID- 11846665
TI  - Generality of solvation effects on the hydrolysis rates of phosphate monoesters
      and their possible relevance to enzymatic catalysis.
AB  - Previous work by Kirby and co-workers revealed a significant acceleration of the
      rate of hydrolysis of p-nitrophenyl phosphate by added dipolar solvents such as
      DMSO. Activation parameters and kinetic isotope effects have been measured to
      ascertain the origin of this effect. The generality of this phenomenon was
      examined with a series of esters with more basic leaving groups. Computational
      analyses of the effects of desolvation of dianionic phosphate monoesters were
      carried out, and the possible effect of the transfer from water to the active
      site of alkaline phosphatase was modeled. The results are consistent with a
      desolvation-induced weakening of the P-O ester bond in the ground state. Other
      aryl phosphate esters show similar rate accelerations at high fractions of DMSO,
      but phenyl and methyl phosphates do not, and their hydrolysis reactions are
      actually slowed by these conditions.

PMID- 11846668
TI  - Cobalt carbonyl-mediated carbocyclizations of enynes: generation of
      bicyclooctanones or monocyclic alkenes.
AB  - Depending on the thermolytic conditions, dicobalthexacarbonyl-complexed enynes
      underwent cyclizations to provide different carbocyclic frameworks.
      Bicyclopentanones were formed from enyne-Co2(CO)6 complexes, or from enynes that
      were treated with Co2(CO)8, or more effectively, with Co4(CO)12 in an alcoholic
      solvent under a H2 or N2 atmosphere. This transformation proceeded via a
      sequential cyclocarbonylation and 1,4-reduction and is the first account using
      the cobalt carbonyl cluster. Under these conditions a cobalt hydride was
      presumably generated, which mediated reduction of the enone to the saturated
      ketone. In contrast, thermolysis of dicobalthexacarbonyl-complexed enynes under a
      hydrogen atmosphere in toluene resulted in their reductive cyclization to form
      monocyclic alkenes in moderate yields, in addition to the bicyclopentenone
      product. In some cases, addition of a hydrosilane to the reaction induced a
      complete suppression of the bicyclopentenone formation. While the former results
      demonstrate a reaction that occurs after the cycloaddition, the latter depicts
      another example of an interruption of the normal route in the Pauson-Khand
      reaction pathway.

PMID- 11846667
TI  - Head-to-backbone cyclization of peptides on solid support by nucleophilic
      aromatic substitution.
AB  - A new versatile synthetic route is presented for the cyclization of tripeptides
      on solid support using nucleophilic aromatic substitution in the cyclization
      step. Identification of all conformers within a limit of 3 kcal/mol from the
      identified global minimum conformations by Monte Carlo conformational searching
      reveals that five out of six synthesized compounds have well-defined peptide
      backbone conformational properties. This was determined by clustering the
      identified conformers against a filter of seven to nine torsion angles in the
      peptide backbone. Thus, the results meet our goal to find synthetic routes to
      peptides that are conformationally sufficiently locked to serve as convenient
      leads for further development of pharmacophoric models. The strategy is based on
      Fmoc-peptide chemistry on a N-aminoethyl-substituted glycine bound to the
      commercially available Rink amide PS-resin. After deprotection of the N-terminus
      of the tripeptide, it is acylated with a fluoronitrobenzoic acid. Subsequently, a
      Boc group on the N-bound aminoethyl substituent is selectively deprotected
      allowing cyclization from the head (N-terminus) to the backbone substituent,
      thereby leading to the desired cyclized tripeptides. A number of representative
      examples of peptides cyclized by this method have been synthesized and
      characterized by NMR. Protecting groups that allow the incorporation of side
      chain functionalized amino acids have been found. Thus, the route provides access
      to generic libraries of conformationally restricted peptide sequences expressing
      a range of proteinogenic pharmacophores.

PMID- 11846669
TI  - Photochemical synthesis, conformational analysis, and transformation of
      [60]fullerene-o-quinodimethane adducts bearing a hydroxy group.
AB  - The photochemical reactions of [60]fullerene with various aromatic aldehydes or
      ketones 1a-n carrying an alkyl group at the ortho position were examined. Some of
      them afforded stable o-quinodimethane adducts 2 with a hydroxy group attached to
      the cyclohexene ring. The adducts 2 were found to adopt one or both of two
      conformers A and E, which possess pseudoaxial and pseudoequatorial hydroxy
      groups, respectively. The conformer ratios depended remarkably on the
      substituents attached to the aromatic nucleus and the cyclohexene ring. The
      dynamic behavior of 2 was also investigated by the VT-NMR technique.

PMID- 11846670
TI  - Anhydrodihydroartemisinin and its 10-trifluoromethyl analogue: access to novel d
      ring-contracted artemisinin trifluoromethyl ketones.
AB  - The preparation of the 10-trifluoromethyl hydroartemisinin, followed by
      dehydration, afforded the trifluoromethyl analogue 2 of anhydrodihydroartemisinin
      1. The reactivity of these two glycals of artemisinin were compared in
      epoxidation and halogenation reactions. Iodination of glycal 1 in water and the
      further rearrangement of the produced iodo hemiacetal provided the new D-ring
      contracted aldehyde 8alpha, where the methyl at C-9 is beta. Epoxidation of 10
      trifluoromethyl anhydrodihydroartemisinin 2 stereoselectively provided the beta
      epoxy ether 11 in high yield. When treated with hexafluoro-2-propanol or
      trifluoroethanol, 11 readily underwent a rearrangement yielding to the D-ring
      contracted trifluoromethyl ketone 9alpha with retention of configuration at C-9.

PMID- 11846671
TI  - Enzymatic kinetic resolution and chemoenzymatic dynamic kinetic resolution of
      delta-hydroxy esters. An efficient route to chiral delta-lactones.
AB  - A successful kinetic resolution of a racemic mixture of delta-hydroxy esters 1
      was obtained via lipase-catalyzed transesterification (E value up to 360). The
      combination of the enzymatic kinetic resolution with a ruthenium-catalyzed
      alcohol racemization led to an efficient dynamic kinetic resolution (ee up to 99%
      and conversion up to 92%). The synthetic utility of this procedure was
      illustrated by the practical syntheses of delta-lactones (R)-6-methyl- and (R)-6
      ethyl-tetrahydropyran-2-one and (S)-5-(tert-butyldimethylsiloxy)heptanal. The
      former are important building blocks in the synthesis of natural products and
      biologically active compounds, and the latter is a key intermediate in the
      synthesis of widely used commercial insecticide Spinosyn A.

PMID- 11846672
TI  - Synthesis of monoacyl A-ring precursors of 1alpha,25-dihydroxyvitamin D3 through
      selective enzymatic hydrolysis.
AB  - An efficient synthesis of monoacylated 1alpha,25-dihydroxyvitamin D3 A-ring
      precursors 15, 16, 18, and 19 has been described through an enzymatic hydrolysis
      process. Candida antarctica A lipase (CAL-A) hydrolyzes the C-5 acetate ester in
      trans stereoisomers 9 and 13, with complete and high selectivity, respectively.
      In the case of cis isomers 11 and 14, Chromobacterium viscosum lipase (CVL) is
      the enzyme of choice, exhibiting opposite selectivity for these two enantiomers.
      This lipase selectively catalyzes the hydrolysis at the C-3 acetate in diester 11
      and at C-5 position in diester 14. It is noteworthy that through a hydrolysis
      reaction CAL-A and CVL allow the synthesis of the four A-ring monoacetylated
      precursors of 1alpha,25-dihydroxyvitamin D3, precursors which are complementary
      to those obtained by the enzymatic acylation process. In addition, with excellent
      yield CVL selectively hydrolyzes the C-3 chloroacetate ester instead of the C-5
      acetate in diester 22, a key intermediate in the synthesis of new A-ring modified
      1alpha,25-dihydroxyvitamin D3 analogues.

PMID- 11846673
TI  - Investigation of bis(tributyltin)-initiated free radical cyclization reactions of
      4-pentenyl iodoacetates.
AB  - Bis(tributyltin)-initiated atom transfer cyclization reactions of 4-pentenyl
      iodoacetates (1) at 80 degrees C led to the formations of 5-(3-iodopropyl)
      substituted dihydro-2(3H)-furanones (3) in high yield. With BF3*Et2O as the
      catalyst, the reactions were run at room temperature to afford the corresponding
      gamma-iodoheptanolactones (2), which could be further transformed into 3
      (tetrahydro-2-furyl)propanoic acids (6) upon treatment with aqueous NaHCO3. The
      reaction mechanism was postulated to be the 8-endo free radical cyclization to
      generate gamma-iodoheptanolactones which easily underwent intramolecular
      nucleophilic substitution to form bicyclic acylium species (7) as the key
      intermediate. Subsequent attack by iodide ion furnished gamma-lactones while
      attack by hydroxide ion gave the tetrahydrofuran derivatives.

PMID- 11846674
TI  - Competitive reaction pathways in the nucleophilic substitution reactions of aryl
      benzenesulfonates with benzylamines in acetonitrile.
AB  - The reactions of aryl benzenesulfonates (YC6H4SO2OC6H4Z) with benzylamines
      (XC6H4CH2NH2) in acetonitrile at 65.0 degrees C have been studied. The reactions
      proceed competitively by S-O (kS-O) and C-O (kC-O) bond scission, but the former
      provides the major reaction pathway. On the basis of analyses of the Hammett and
      Bronsted coefficients together with the cross-interaction constants rho(XY),
      rho(YZ), and rho(XZ), stepwise mechanisms are proposed in which the S-O bond
      cleavage proceeds by rate-limiting formation of a trigonal-bipyramidal
      pentacoordinate (TBP-5C) intermediate, whereas the C-O bond scission takes place
      by rate-limiting expulsion of the sulfonate anion (YC6H4SO3-) from a Meisenheimer
      type complex.

PMID- 11846675
TI  - Effects of host-guest recognition on kinetics of Diels-alder reaction of
      quinocrown ethers with cyclopentadiene.
AB  - Diels-Alder reactions of 15-21-membered quinocrown ethers 1a-c and 18-membered
      quinobenzocrown ether 1d with cyclopentadiene were catalyzed by the addition of
      alkali, alkaline earth metal and ammonium perchlorates, and scandium
      trifluoromethane-sulfonate. The alkali metal and ammonium ions brought about a
      fairly selective rate-acceleration for each crown ether due to the size-fitted
      ion-in-the-hole complexation. However, such a hole-size-selectivity was not
      observed for the reactions catalyzed by divalent alkaline-earth (Mg2+ to Ba2+)
      and trivalent Sc3+ ions. The wrapping complexation played a significant role in
      rate-acceleration in such a way that the smallest Mg2+ caused 160 times rate
      enhancement for the most flexible 1c and the Sc3+ performed maximal 3700 times
      rate-increment for the 18-membered quinobenzocrown 1d. These effects of cation
      recognition were rationalized by the reduction of LUMO energy that is favored by
      the orbital interaction with the HOMO of cyclopentadiene. The magnitude of rate
      enhancement was discussed in terms of the cation binding affinity and
      coordination geometry of quinocrown ethers as well as the valence of cations.

PMID- 11846677
TI  - Preparation and NMR study of silylated carboxonium ions.
AB  - A series of silylated carboxonium ions, 2a-6a, were prepared as long-lived
      species by treating triethylsilane and triphenylmethyl
      tetrakis(pentafluorophenyl)borate (Ph3C(+)B(C6F5)4-) with ketones, enones,
      carbonates, amides, and urea in CD2Cl2 solution. They were characterized by 13C
      and 29Si NMR spectroscopy at -78 degrees C. The NMR study indicates that the
      silylated carbonyl compounds are resonance hybrids of oxocarbenium and
      carboxonium ions, while the latter are the major contributors to the overall
      structures. The structure and 13C and 29Si NMR chemical shifts of the model
      trimethylsilylated carboxonium ions were also calculated by density functional
      theory/IGLO methods. The calculated results agree well with the experimental
      data.

PMID- 11846676
TI  - Asymmetric synthesis of the protoberberine alkaloid (S)-(-)-xylopinine using
      enantiopure sulfinimines.
AB  - A concise enantioselective synthesis of (S)-(-)-xylopinine (1) is described
      involving the addition of the laterally lithiated derivative of o-tolunitrile of
      16 to enantiopure sulfinimine (+)-14. Treatment of the resulting cyano
      sulfinamide adduct (-)-17b with DIBAL-H accomplishes five operations in a single
      pot and furnishes the cyclic imine (+)-18 in good yield. Reduction and
      cyclization affords (S)-(-)-1. Alternatively basic hydrolysis of 17b,c gives
      isoquinolone 21 that is cyclized and reduced to give (S)-(-)-1.

PMID- 11846678
TI  - Synthesis and properties of spiro nucleosides containing the barbituric acid
      moiety.
AB  - The two chiral spiro nucleosides 4 and 5 containing the barbituric acid moiety
      were efficiently synthesized from optically pure precursors, and their properties
      were studied. The carbocyclic nucleoside 5 is considerably more stable against
      ring opening than the deoxyribosyl derivative 4. Both compounds present enhanced
      hydrogen bonding capacity with diacetyladenosine.

PMID- 11846679
TI  - A Highly diastereoselective synthesis of (1R)-(+)-camphor-based chiral allenes
      and their asymmetric hydroboration-oxidation reactions.
AB  - Synthesis of camphor derived chiral allenes and their hydroboration-oxidation
      reactions are described. Reaction of (1R)-(+)-camphor with alkynyllithium
      followed by the reduction of the resulted propargyl alcohol derivatives using
      AlH3 furnished chiral allenes 2a-g in excellent yields with high
      diastereoselectivity. Reduction of the propargyl alcohols with aluminum hydride
      proceeded through selective intermolecular anti-addition of hydride ion. The
      stereochemistry of the chiral allenes 2 was assigned based on lanthanide shift
      studies and chemical correlations. Diastereoselectivity was observed in the
      hydroboration-oxidation of 2 which produced a mixture of (E,R) and (E,S)
      stereoisomers in a ratio of 6:1 to 18:1.

PMID- 11846680
TI  - Hydroxylated pyrrolidines. Enantiospecific synthesis of all-cis 2,3,4,5
      substituted pyrrolidine derivatives from serine.
AB  - We report the enantiospecific synthesis of the sterically congested all-cis
      2,3,4,5-substituted pyrrolidines 4, 5, and 6, from either D- or L-serine.
      Hemiaminal intermediate 13 is converted to the fully substituted pyrrolidine 15
      by way of a tandem Wittig-Michael reaction. The endo stereochemistry of the C-3
      methyl group of compound 15 is set by stereoselective reduction of the double
      bond in 11, driven by a preference for hydrogenation from the rear side of the
      molecule. The all-cis configuration of these fully substituted pyrrolidines has
      been established by X-ray analysis of compound 6. Removal of the benzenesulfonyl
      group from the highly substituted and functionalized intermediate 15 is
      successfully accomplished by sodium naphthalenide reduction.

PMID- 11846681
TI  - Characterization of rotameric mixtures in o- and m-substituted benzaldehydes by
      matrix isolation IR spectroscopy.
AB  - The cis and trans conformers of benzaldehydes substituted in the o- or m
      positions by Cl or CN can be differentiated by IR spectroscopy in Argon matrices.
      Partial photochemical rotamerization allows assignment of the IR bands and
      establishment of their relative intensities in pairs of rotamers, which permits,
      in turn, quantitation of equilibrium compositions prior to photolysis. The
      observed spectra and equilibrium compositions are in very good agreement with the
      predictions of vibrational spectra and free energy differences from B3LYP/6-31G
      calculations. The present work represents the first attempt to quantitate the
      small contributions that the cis rotamers make to the room-temperature
      equilibrium compositions of the two o-substituted benzaldehydes. The results for
      the m-substituted derivatives are compared to earlier estimates based on other
      methods.

PMID- 11846682
TI  - Preparation and structural characterization of polymer-supported methylrhenium
      trioxide systems as efficient and selective catalysts for the epoxidation of
      olefins.
AB  - Novel heterogeneous compounds of methylrhenium trioxide (MTO) were prepared with
      poly(4-vinylpyridine) and polystyrene as polymeric supports. The wide-angle X-ray
      diffraction (WAXS.) analysis, performed by the application of the difference
      method, showed, in a representative case of the poly(4-vinylpyridine)/MTO
      derivatives, a slightly distorted octahedral conformation on the metal's primary
      coordination sphere. The Re-O and Re-C bond distances were not influenced by the
      polymeric nature of the ligand, while the Re-N bond distance was abnormally
      shorter than those previously observed for homogeneous MTO/L(n) complexes,
      showing a strong coordination of the rhenium atom to the support. A set of
      scanning electron microscopy (SEM) photographs showing the morphology of the
      surface of particles of poly(4-vinylpyridine)/MTO and polystyrene/MTO systems are
      reported. The reticulation grade of the polymer was a crucial factor for the
      morphology of the particles surface. Poly(4-vinylpyridine) 2% cross-linked
      systems were characterized by particles with very irregular shape and surface.
      Poly(4-vinylpyridine) 25% cross-linked systems showed particles with regular
      spherical shape, which morphology was similar to microcapsules obtained with
      polystyrene. All novel MTO compounds were efficient and selective heterogeneous
      catalysts for the epoxidation of olefins using environmentally friendly H2O2 as
      oxygen atom donor. The catalyst activity was maintained for at least five
      recycling experiments.

PMID- 11846683
TI  - To what extent can aromaticity be defined uniquely?
AB  - Statistical analyses of quantitative definitions of aromaticity, ASE (aromatic
      stabilization energies), RE (resonance energies), Lambda (magnetic susceptibility
      exaltation), NICS, HOMA, I5, and A(J), evaluated for a set of 75 five-membered pi
      electron systems: aza and phospha derivatives of furan, thiophene, pyrrole, and
      phosphole (aromatic systems), and a set of 30 ring-monosubstituted compounds
      (aromatic, nonaromatic, and antiaromatic systems) revealed statistically
      significant correlations among the various aromaticity criteria, provided the
      whole set of compounds is involved. Hence, broadly considered, the various
      manifestations of aromaticity are related and aromaticity can be regarded
      statistically as a one-dimensional phenomenon. In contrast, when comparisons are
      restricted to some regions or groups of compounds, e.g., aromatic compounds with
      ASE > 5 kcal/mol or polyhetero-five-membered rings, the quality of the
      correlations can deteriorate or even vanish. In practical applications,
      energetic, geometric, and magnetic desriptors of aromaticity do not speak with
      the same voice. Thus, in this sense, the phenomenon of aromaticity is regarded as
      being statistically multidimensional.

PMID- 11846684
TI  - NMR studies on epoxidations of allenamides. Evidence for formation of nitrogen
      substituted allene oxide and spiro-epoxide via trapping experiments.
AB  - Two epoxidations of chiral allenamides are described here. While treatment with m
      CPBA led to highly stereoselective formation of an alpha-keto aminal that can be
      useful synthetically, DMDO oxidation led to conclusive evidence for both nitrogen
      substituted allene oxide (via mono-epoxidation) and spiro-epoxide (via bis
      epoxidation) using intramolecular nucleophilic trapping experiments. NMR studies
      provide reliable evidence for a 3-oxetanone that can be derived from the spiro
      epoxide and also suggest the presence of an allene oxide. Despite a facile second
      epoxidation as evidenced by the predominant formation of the 3-oxetanone, in the
      presence of furan, [4 + 3] cycloaddition of the nitrogen-substituted allene oxide
      or oxyallyl cation with furan occurs faster than the second epoxidation
      efficiently leading to cycloadducts. This rate difference plays an invaluable
      role for the success of a stereoselective sequential epoxidation-[4 + 3]
      cycloaddition reaction via DMDO epoxidations of chiral allenamides.

PMID- 11846685
TI  - 2-amino-substituted 1-sulfinylferrocenes as chiral ligands in the addition of
      diethylzinc to aromatic aldehydes.
AB  - A simple and modulable access to a structural variety of enantiopure amino
      substituted ferrocenyl sulfoxides and their use as chiral catalysts in the
      asymmetric addition of diethylzinc to aromatic aldehydes is described. Moderate
      to high enantioselectivities (up to 96% ee) were obtained in the case of the
      arylsulfonamide ligands (R(Fc), R(S))-4h and (R(Fc), R(S))-4i. It has been
      demonstrated that the planar chirality of the ferrocene unit is the decisive
      chiral element involved in the reaction.

PMID- 11846686
TI  - Arylpentazoles revisited: experimental and theoretical studies of 4
      hydroxyphenylpentazole and 4-oxophenylpentazole anion.
AB  - Kinetic measurements for the degradation of 4-hydroxyphenylpentazole (2a) and its
      salt 2b-NBu4 in CD3OD and in CD2Cl2 provided a set of activation parameters. The
      resulting free energies of activation in methanol (DeltaG298 = 19.7 kcal/mol for
      2a and DeltaG298 = 20.6 kcal/mol for 2b-NBu4) were compared with previous results
      for the 4-chloro derivative, 2c, and collectively correlated with results of gas
      phase calculations at the B3LYP/6-31+G(d,p) level of theory. This, and another
      linear correlation of the seven computed DeltaG298 values with the previously
      reported kinetic data of Ugi and Huisgen, gave the basis for the estimation of
      the stability of pentazole anion (1) and its derivatives in solutions. Thus, N5(
      ) is predicted to have t(1/2) = 2.2 d, while the half-lifetime for HN5 is
      expected to be only about 10 min in methanol at 0 degrees C. Controlled
      ozonolysis of 2b-NBu4 followed by 1H and 15N NMR spectroscopy shows a
      preferential destruction of the N5 ring, which excludes it from possible methods
      for preparation of the parent pentazole.

PMID- 11846687
TI  - Synthesis of allenes from allylic alcohol derivatives bearing a bromine atom
      using a palladium(0)/diethylzinc system.
AB  - A general and efficient synthesis of allenes using a palladium(0)/diethylzinc
      system is described. Treatment of mesylates or trichloroacetates of (E)- or (Z)-2
      bromoalk-2-en-1-ols with diethylzinc in the presence of a catalytic amount of
      palladium(0) affords allenes bearing an aminoalkyl, alkyl, or aryl substituent(s)
      in good to high yields. No transfer of chirality from the stereogenic center
      carrying the mesyloxy group to the allene was observed.

PMID- 11846688
TI  - A CD exciton chirality method for determination of the absolute configuration of
      threo-beta-aryl-beta-hydroxy-alpha-amino acid derivatives.
AB  - The absolute configuration of threo-beta-aryl-beta-hydroxy-alpha-amino acids was
      studied by CD exciton chirality method using 7-diethylaminocoumarin-3-carboxylate
      as a red-shifted chromophore. Bischromophoric derivatives for a series of threo
      beta-aryl-beta-hydroxy-alpha-amino acids (3a-h) were prepared and their CD
      spectra measured in CH2Cl2. By combining the data of CD and NMR coupling
      constants, we are able to correlate their preferred conformer (B) and the
      positive CD to the corresponding (2S,3R)-absolute configuration. These results
      are consistent with those obtained from serine and threonine derivatives, which
      represent the simplest form of beta-hydroxy-alpha-amino acids. This CD method
      could thus become a general method for determining the absolute configuration of
      threo-beta-aryl-beta-hydroxy-alpha-amino acids.

PMID- 11846689
TI  - Chromogenic azo-coupled calix[4]arenes.
AB  - Novel 1,3-alternate calix[4]azacrowns having an azo chromophoric pendent group
      were synthesized, and their 1,3-alternate conformations were confirmed by X-ray
      crystal structure. In view of the hypsochromical UV band shifting upon cation
      complexation, azo-coupled calix[4]azacrown-5 (3) showed the most selective
      shifting with alkali and alkaline metal ions. In addition, 3 revealed K+ ion
      selectivity not only due to the size comparability between the K+ ion and the
      azacrown-5 loop but also due to a significant K+-pi interaction between the two
      aromatic rings and the K+ ion. The UV band shifting is also dependent on the
      lipophilicity of the species of counteranion used.

PMID- 11846690
TI  - Synthesis of a sialic acid dimer derivative, 2'alpha-O-benzyl Neu5Ac-alph-(2-
      >5)Neu5Gc.
AB  - The preparation of a disaccharide 2, Neu5Ac-alpha-(2-->5)Neu5Gc having a alpha
      benzyl protecting group at the reducing end, by the coupling of the easily
      accessible building units 4 and 5 is described. Subsequent deprotection of the
      coupling adduct led to the isolation of the target compound 2 in high yield.

PMID- 11846691
TI  - Domino metathesis of 2-azanorbornenones: a new strategy for the enatioselective
      synthesis of 1-azabicyclic compounds.
AB  - Domino metathesis of N-alkylated derivatives of (1S)-2-azanorborn-5-en-3-one
      allowed for the enantioselective synthesis of pyrrolizidine, quinolizidine,
      pyrrolidinoazepine, and pyrrolidinoazocine derivatives in a straightforward
      process.

PMID- 11846692
TI  - An efficient and highly selective deprotecting method for beta
      (trimethylsilyl)ethoxymethyl ethers.
AB  - A series of beta-(trimethylsilyl)ethoxymethyl ethers were hydrolyzed to their
      corresponding alcohols in high yields by using a catalytic amount of CBr4 (15%)
      in MeOH under refluxing reaction conditions. The chemoselective deprotection
      between trialkylsilyl and beta-(trimethylsilyl)ethoxymethyl-protected alcohols
      can be achieved by using an alcohol with steric hindrance such as iPrOH. The
      selectivity also can be achieved in the CBr4/MeOH reaction mixture under
      ultrasonic reaction conditions.

PMID- 11846694
TI  - Synthesis of the first nonmetalated triazolephthalocyanine derivatives.
AB  - The synthesis of nonmetalated triazolephtahlocyanines is described for the first
      time. These compounds have been prepared by both one-step and stepwise
      procedures. Their spectroscopic data reveal a nonaromatic cross-conjugated 18pi
      electron structure in contrast to their aromatic metalated derivatives.

PMID- 11846693
TI  - Rearrangements of cyclobutenones. Electrocyclic ring closure and thermal ring
      expansions of 3-allenyl- and 3-alkynyl-2-dienyl-4,4-dimethoxycyclobutenones.
AB  - Thermal rearrangements of 2-allenyl- and 2-alkynyl-3-(2-ethenylphenyl)-4,4
      dimethoxycyclobutenones were studied. At ambient temperature, the allenyl
      compounds undergo an electrocyclic cascade to give bicyclo[4.2.0]octadienyl-fused
      cyclobutenones. These unusual tetracyclic cyclobutenones were shown to be viable
      synthetic precursors to benzo[a]anthracene-7,12-diones, compounds representing
      the framework of the angucycline group of naturally occurring antibiotics. In
      contrast, the 2-alkynylcyclobutenones are stable at ambient temperature but
      undergo a facile rearrangement at 110 degrees C (toluene) to give the previously
      unknown naphthalene derivatives, 1,2-dihydro-2,2-dimethoxy-1-(3
      alkenylidene)naphtho[2,1-b]furans.

PMID- 11846695
TI  - Enantioselective synthesis of marine indole alkaloid hamacanthin B.
AB  - An enantioselective total synthesis of hamacanthin B (1) is described. This
      synthesis is based on the asymmetric synthesis of (S)-2-azido-(indol-3
      yl)ethylamine 7, which is coupled with the 3-indolyl-alpha-oxoacetyl chloride 8
      and subsequently used in a successful intramolecular Staudinger-aza Wittig
      cyclization to form the central dihydropyrazinone ring. The stereochemistry of
      naturally isolated hamacanthin B is revealed as the (S)-configuration.

PMID- 11846696
TI  - Regioselective and stereoselective nucleophilic ring opening reactions of a
      phenyl-substituted aziridine: enantioselective synthesis of beta-substituted
      tryptophan, cysteine, and serine derivatives.
AB  - The asymmetric synthesis of beta-phenyl-substituted cysteine, tryptophan, and
      serine derivatives was successfully developed. In this approach, the key
      intermediate, enantiomerically pure 3-phenylaziridine-2-carboxylic ester 7, was
      prepared from alpha,beta-unsaturated ester 1 by employing the Sharpless
      asymmetric dihydroxylation. The aziridine 7 was treated with 4
      methoxybenzylthiol, indole, and acetic acid to give beta-phenyl-substituted
      cysteine, tryptophan, and serine, respectively, in a clean S(N)2 type ring
      opening at the C3 position. This general approach can be used to synthesize a
      variety of beta-substituted novel amino acids.

PMID- 11846697
TI  - Porphyrin architectures bearing functionalized xanthene spacers.
AB  - A modular synthetic strategy for the construction of cofacial porphyrin
      architectures bearing hydrogen-bond synthons on a xanthene platform is presented.
      The convergent approach is based on a xanthene aldehyde-ester building block that
      is easily obtainable on a multigram scale with minimal purification. Treatment of
      this xanthene derivative with a variety of aryl aldehydes and pyrrole under
      standard Lindsey conditions affords a family of meso-substituted porphyrins
      bearing a single functionalized xanthene spacer. Direct modification of the
      hydrogen-bond synthon after macrocyclization proceeds smoothly to furnish
      porphyrin systems with a variety of cofacial functionalities (e.g., carboxylic
      acid, ester, amide). Porphyrins bearing two trans-functionalized xanthene spacers
      are prepared by the MacDonald [2 + 2] condensation of the xanthene aldehyde-ester
      with readily available 5-aryl-substituted dipyrromethanes such as 5
      mesityldipyrromethane to afford the pure alpha,alpha- and alpha,beta-porphyrin
      atropisomers after chromatographic separation. The versatility of this synthetic
      method offers intriguing opportunities for the use of these and related templates
      for the study of proton-coupled activation of small molecules.

PMID- 11846698
TI  - Palladium(0)-catalyzed coupling of organozinc iodide reagents with
      bromopyridines: synthesis of selectively protected pyridine-containing
      azamacrocycles.
AB  - The synthesis of azamacrocycles in which the ring nitrogens are regioselectively
      functionalized is described. An organozinc palladium(0)-catalyzed coupling with
      an appropriately functionalized bromopyridine generated a key intermediate, which
      was transformed in two steps to a desired precursor and subjected to an
      intramolecular N-alkylation to effect a macrocyclization affording selectively
      protected azamacrocycles 1-3.

PMID- 11846700
TI  - Cycloisomerization of omega-aryl-1-alkynes: GaCl3 as a highly electrophilic
      catalyst for alkyne activation.
AB  - Cycloisomerization of a variety of omega-aryl-1-alkynes, where omega = 5 or 6, in
      the presence of a catalytic amount of GaCl3 provided dihydronaphthalene
      derivatives or dihydrobenzocycloheptenes, respectively, in high yields.

PMID- 11846699
TI  - An improved synthesis of a trifurcated newkome-type monomer and orthogonally
      protected two-generation dendrons.
AB  - The one-step synthesis of amino-polyether tri-tert-butyl ester monomer 2, by
      condensation of TRIS with tert-butyl acrylate, is reported. The nitrogen of the
      monomer can be protected with a Cbz group; subsequent removal of the tert-butyl
      esters with formic acid affords a triacid that is coupled to three monomers to
      afford an orthogonally protected two-generation, trifurcated polyether-polyamide
      dendron. The Cbz protecting group may be removed from the second-generation
      dendron without disturbing the tert-butyl esters of the periphery.

PMID- 11846702
TI  - Immunolocalization of transforming growth factor-beta 3 in pregnant human
      myometrium.
AB  - BACKGROUND: Transforming growth factor-beta 3 is a cytokine which is involved in
      cell growth regulation and differentiation, stimulation of extracellular matrix
      and modulation of immune responses. The goal of this study was to detect the
      presence of this cytokine in the myometrium of preterm and term, nonlaboring and
      laboring patients, and to measure serum levels of interleukin-1 beta (IL-1 beta),
      IL-6 and IL-8 before cesarean section. METHODS: In this prospective study, we
      obtained samples of myometrium from the lower uterine segment during elective and
      emergency cesarean sections (term non-laboring, n=8; term laboring, n=7; preterm
      non-laboring, n=3; and preterm laboring, n=19) and stained for transforming
      growth factor-beta 3. Blood was also sampled from the same patients to determine
      IL-1 beta, IL-6 and IL-8 levels. RESULTS: Different intensities of staining were
      detected in preterm laboring, term nonlaboring and term laboring groups, but
      there was no staining in preterm nonlaboring group. We also found a statistically
      significant difference in IL-6 levels between laboring and nonlaboring groups
      (p=0.028). CONCLUSION: Different intensities of TGF-beta 3 which appeared in
      different stages of myometrium made us consider that TGF-beta 3 might prepare
      myometrium to labor, and IL-6 was more important than the other interleukins in
      initiation of labor.

PMID- 11846703
TI  - Identification of the major proteoglycans from human myometrium.
AB  - BACKGROUND: During pregnancy and parturition a remodeling within the
      extracellular matrix of the cervix and the corpus uteri occurs, which is of
      fundamental importance to a normal labor. The aim of this study is to identify
      the major proteoglycans in corpus uteri of non-pregnant subjects. METHODS: From
      human uterine tissue proteoglycans were extracted and purified using CsCl-density
      gradient centrifugation, gel and ion-exchange chromatography. The proteoglycans
      were quantified and identified by Alcian Blue before and after ABC-digestion and
      by Western blotting. RESULTS: The results showed that the corpus uteri contains a
      substantial amount of proteoglycans, 1.825 microg/mg wet weight. Decorin is
      dominating, constituting 63% of the total amount of proteoglycans. Heparan
      sulphate proteoglycans accounted for 20% and biglycan for 16%. Less than 1%
      consisted of the large proteoglycan versican. CONCLUSIONS: Further investigations
      must be performed to provide more information of the biological role of the
      proteoglycans in the uterus, especially during labor, by the presence of heparan
      sulphate proteoglycans and the minute presence of versican which indicate that
      the proteoglycan composition and organization is different to that of the cervix.

PMID- 11846704
TI  - Perinatal deaths and insufficient antenatal care in Latvia.
AB  - OBJECTIVE: A national audit on perinatal deaths was performed to assess the
      quality of antenatal care, and to suggest measures for improved antenatal care.
      MATERIAL AND METHODS: Medical records of all the perinatal deaths in Latvia in
      the years 1995-1996 have been studied. Non-attenders and attenders of antenatal
      care were characterized by socio-economic and medical variables: maternal age,
      parity, history of perinatal outcome, health status and behavioral hazards during
      the index pregnancy, length of gestation and birth weight. The Nordic-Baltic
      perinatal death classification was used. RESULTS: In 85 of 442 cases (19%) of
      perinatal deaths women had not taken advantage of antenatal care provided for
      them. Non-attenders were more likely to be smokers (p<0.001) and alcohol abusers
      (p<0.005), above 35 years of age (p<0.005), and had higher parity (p<0.001). Non
      attenders more often had systemic diseases and pregnancy complications. Neonatal
      complications, such as congenital syphilis (p<0.05) and other infections
      (p<0.05), were more common among non-attenders. There was no difference in rates
      of preterm birth and low birth weight between attenders and non-attenders.
      CONCLUSIONS: One fifth of mothers with perinatal death did not attend ANC, and in
      some women who attended ANC, lack of intervention was related to the perinatal
      death.

PMID- 11846705
TI  - Ambulatory blood pressure as predictor of preeclampsia in diabetic pregnancies
      with respect to urinary albumin excretion rate and glycemic regulation.
AB  - BACKGROUND: Twenty-four-hour ambulatory blood pressure was evaluated as a
      predictor of preeclampsia in women with insulin-dependent diabetes mellitus with
      respect to urinary albumin excretion rate and glycemic regulation. METHODS: One
      hundred and fifty-one women with insulin-dependent diabetes mellitus were
      consecutively recruited from the outpatient maternity ward for 24 hour ambulatory
      blood pressure measurement with a portable monitor (SpaceLab 90207). Blood
      pressure was measured three times during pregnancy and once after delivery.
      Evaluation was performed with receiver-operator-characteristics curves in
      primiparous women. Stratified analysis and multiple regression was applied with
      respect to urinary albumin excretion rate, HbA1c, age, duration of diabetes
      mellitus, uric acid, and BMI. RESULTS: The incidence of preeclampsia was
      significantly associated with increasing urinary albumin excretion rate,
      primiparity, and ambulatory blood pressure. Ambulatory blood pressure was
      associated with HbA1c throughout pregnancy adjusted for urinary albumin excretion
      rate. The ambulatory blood pressure was higher from first trimester throughout
      pregnancy in women developing preeclampsia compared to women who did not have
      preeclampsia. The best sensitivity and specificity for predicting preeclampsia in
      primiparous women were at cut-off values of systolic and diastolic day ambulatory
      blood pressure above 122 and 74 mmHg, respectively. The relative risk of
      preeclampsia was significantly higher when ambulatory blood pressure was above
      the cut-off values and increased further with higher urinary albumin excretion
      rate. CONCLUSIONS: The relationship between ambulatory blood pressure and
      preeclampsia is not confined to women with macroalbuminuria but is also present
      in women with normo- and microalbuminuria. Poor glycemic control and increased
      urinary albumin excretion rate is associated with preeclampsia when ambulatory
      blood pressure is above cut-off values of 122/74 mmHg (systole/diastole).
      Ambulatory blood pressure is a reliable measurement for prediction of
      preeclampsia in primiparous women with insulin-dependent diabetes mellitus.

PMID- 11846706
TI  - Four years experience of first-trimester nuchal translucency screening for fetal
      aneuploidies with increasing regional availability.
AB  - BACKGROUND: A prospective screening study was carried out at the regional genetic
      and perinatal center in South Hungary in order to determine the efficiency of
      first-trimester nuchal translucency screening for fetal aneuploidies, following
      augmentation of the availability of nuchal translucency screening in the region
      by the inclusion of newly-trained hospital sonographers. METHODS: Nuchal
      translucency thickness was measured by transvaginal sonography in 7,044 women
      with singleton or multiple pregnancies at weeks 10-12. Fetal karyotyping was
      performed when the nuchal translucency was . or = 2.5 mm, and in women with
      fetuses at high cytogenetic risk. RESULTS: Follow-up was performed in 6,841 of
      the 7,044 screened women. An abnormal karyotype was found in 33 cases (0.48%).
      The level of increased nuchal translucency was 4.5% at a cutoff of > or = 2.5 mm,
      and 2.8% at a cutoff of > or = 3 mm. Seventeen cases of trisomy 21, eight of
      trisomy 18, four of trisomy 13, one of 45,X, one of triploidy and two cases with
      other chromosomal abnormalities were detected. In the 33 fetuses with a
      chromosomal abnormality, the nuchal translucency thickness was <2.5 mm in a case
      of trisomy 18, > or = 2.5 mm in 32 cases and > or = 3 mm in 28 cases. With
      cutoffs of 2.5 mm and 3 mm, the sensitivity was 96.97% and 84.85%, respectively.
      CONCLUSIONS: Application of a nuchal translucency thickness cutoff of 2.5 mm is
      highly efficient for the screening of fetal aneuploidies at 10-12 weeks. This
      efficiency can be maintained by increasing the regional availability of nuchal
      translucency screening through the inclusion of newly-trained hospital
      sonographers.

PMID- 11846707
TI  - The impact of frozen embryos on emotional reactions during in vitro
      fertilization.
AB  - BACKGROUND: Emotional reactions of couples were investigated during in vitro
      fertilization (IVF) at a private clinic in Sweden. The purpose was to compare
      such reactions between couples who obtained supernumerary embryos that could be
      cryopreserved and couples without such embryos. METHODS: Forty women and men
      undergoing IVF treatment monitored individually their emotional reactions daily
      for one complete treatment cycle from the first day of down-regulation until the
      outcome of treatment was known. Ratings were extracted and analyzed from two
      separate days; the very first day of treatment and the day of embryo transfer.
      RESULTS: The group of women (n=16; 40%) with supernumerary embryos suitable for
      cryopreservation reported a greater increase in optimism than the group (n=24;
      60%) without such embryos (p=0.024). Correspondingly, women with supernumerary
      embryos reported less pessimism than women without such embryos (p=0.014). Among
      men there was no difference in optimism or pessimism between the groups. The
      women and men with supernumerary embryos did not differ in distress reactions
      compared to those women and men without such embryos. There was no correlation
      between optimism and distress on the day of embryo transfer in women; r=-0.167
      and men; r=-0.135 respectively. CONCLUSION: The presence of frozen embryos
      increased optimistic and reduced pessimistic feelings about pregnancy among women
      undergoing IVF treatment. However, the couples' increased optimism on the day of
      embryo transfer did not seem to reduce their experience of distress.

PMID- 11846708
TI  - Induced abortion and placenta complications in the subsequent pregnancy.
AB  - BACKGROUND: To study the risk of placenta complications following an induced
      abortion as a function of the interpregnancy interval. METHODS: This study is
      based on three Danish national registries; the Medical Birth Registry, the
      Hospital Discharge Registry, and the Induced Abortion Registry. All primigravida
      women from 1980 to 1982 were identified in these three registries. A total of
      15,727 women who terminated the pregnancy with a first trimester induced abortion
      were selected to the abortion cohort, and 46,026 women who did not terminate the
      pregnancy with an induced abortion constituted the control cohort. By register
      linkage all subsequent pregnancies were identified from 1980 to 1994. Only women
      who had a non-terminated pregnancy following the index pregnancy were selected to
      the study. Placenta complications were identified using either the Hospital
      Discharge Registry ICD-8 codes or the Medical Birth Registry records. RESULTS: A
      slightly higher risk of placenta complications following an abortion was found.
      Retained placenta occurred more frequently in women with one, two or more
      previous abortions, compared with women without any previous abortion of similar
      gravidity. Adjusting for maternal age and residence at time of pregnancy, the
      interpregnancy interval, and the number of previous miscarriages (control cohort
      only), the odds ratios of retained placenta in deliveries of singleton live
      births in women with one previous abortion was 1.17 (95%CI=1.02-1.35), and for
      women with two or more previous abortions it was 1.68 (95%CI=1.23-2.30),
      respectively, compared with the control cohort of similar gravidity. Only for
      women who had one abortion did the results follow the predicted pattern of a
      higher risk of retained placenta after a short pregnancy interval. No association
      with placenta previa was seen. CONCLUSIONS: The findings suggest a positive
      association between abortions and retained placenta in subsequent singleton live
      births, but the association was weak and confounding cannot be ruled out.

PMID- 11846709
TI  - CO(2) laser vaporization as primary therapy for human papillomavirus lesions. A
      prospective observational study.
AB  - BACKGROUND: Human papillomavirus manifestations occur with increased frequency
      and severity amongst sexually active people. Several therapeutic approaches have
      been suggested to treat this viral disease. The aim of this prospective
      observational study was to assess the effectiveness of CO(2) laser vaporization
      for human papillomavirus warts. MATERIALS AND METHODS: Eighty healthy sexually
      active women with cytologically, colposcopically and histologically diagnosed
      human papillomavirus urogenital and perianal warts were enrolled and then treated
      by CO(2) laser (16-18 W). Male partners were also investigated, and interferon
      beta was eventually administered. All patients were then followed up for twelve
      months consecutively. RESULTS: At twelve-month follow-up, warts clearance was
      observed in 70 (87.5%) women. Recurrence was reported in ten (12.5%) women with
      multiple partners and affected by flat or endophytic condiloma of the cervix.
      Moreover, there were no complaints of pain, scar tissue deformity or other side
      effects. CONCLUSIONS: CO(2) laser vaporization is an effective, as well as safe
      and simple therapeutic approach for treatment of human papillomavirus warts. Its
      use should be encouraged for condyloma acuminata not associated with malignancy,
      as well as during pregnancy.

PMID- 11846710
TI  - Reproductive hormones and stress urinary incontinence in pregnancy.
AB  - BACKGROUND: The cause of transient stress urinary incontinence during pregnancy
      remains uncertain. Anatomical change, such as a pressure effect of the enlarged
      uterus, changes in renal function, and alterations in bladder and urethral
      function have been proposed. There is little information about the role of
      reproductive hormones in stress urinary incontinence with onset during pregnancy.
      METHODS: In a prospective, longitudinal, observational cohort study 200
      consecutive women attending in early pregnancy were observed by repeated
      measurements of stress urinary incontinence, its possible determinants as well as
      serum concentrations of progesterone, estradiol and relaxin. RESULTS: The
      prevalence rate of stress urinary incontinence increased to a stable level of
      about 25% from mid-pregnancy and increased with parity. A higher serum relaxin
      value early in pregnancy was correlated to a lower prevalence rate of stress
      urinary incontinence with onset during pregnancy, also when the influence of
      potentially important factors was taken into account in a multivariate analysis.
      No significant difference was shown regarding serum concentrations of estrogen or
      progesterone, maternal age, weight gain, time since last delivery or smoking,
      although this can be due to a small sample size. CONCLUSION: The reproductive
      hormone relaxin might have a role in maintaining urinary continence during
      pregnancy. A mechanism is uncertain.

PMID- 11846712
TI  - Fistula formation after large loop excision of the transformation zone in
      patients with cervical intraepithelial neoplasia.

PMID- 11846711
TI  - Dilatation and curettage fails to detect most focal lesions in the uterine cavity
      in women with postmenopausal bleeding.
AB  - OBJECTIVE: To determine the prevalence of focally growing lesions in the uterine
      cavity in women with postmenopausal bleeding and endometrium > or = 5 mm and the
      extent to which such lesions can be correctly diagnosed by D&C. METHODS: In a
      prospective study, 105 women with postmenopausal bleeding and endometrium > or =
      5 mm at transvaginal ultrasound examination underwent diagnostic hysteroscopy,
      D&C and hysteroscopic resection of any focally growing lesion still left in the
      uterine cavity after D&C. Twenty-four women also underwent hysterectomy. If the
      histological diagnosis differed between specimens from the same patient, the most
      relevant diagnosis was considered the final one. RESULTS: Eighty percent (84/105)
      of the women had pathology in the uterine cavity, and 98% (82/84) of the
      pathological lesions manifested a focal growth pattern at hysteroscopy. In 87% of
      the women with focal lesions in the uterine cavity, the whole or parts of the
      lesion remained in situ after D&C. D&C missed 58% (25/43) of polyps, 50% (5/10)
      of hyperplasias, 60% (3/5) of complex atypical hyperplasias, and 11% (2/19) of
      endometrial cancers. The agreement between the D&C diagnosis and the final
      diagnosis was excellent (94%) in women without focally growing lesions at
      hysteroscopy. CONCLUSION: If there are focal lesions in the uterine cavity,
      hysteroscopy with endometrial resection is superior to D&C for obtaining a
      representative endometrial sample in women with postmenopausal bleeding and
      endometrium > or = 5 mm.

PMID- 11846713
TI  - Omental pregnancy in a woman taking the progestogen-only pill.

PMID- 11846714
TI  - Cost-effectiveness of recombinant versus urinary follicle stimulating hormone;
      whose point of view?

PMID- 11846715
TI  - Pneumomediastinum secondary to hyperemesis gravidarum during early pregnancy.

PMID- 11846716
TI  - Pelvic spleen: a very rare entity not to be misdiagnosed by the laparoscopic
      surgeon.

PMID- 11846717
TI  - Successful pregnancy after the noninvasive management of uterine arteriovenous
      malformation.

PMID- 11846718
TI  - Pregnancy-associated diffuse cavernous hemangioma of the uterus.

PMID- 11846719
TI  - Low HIV-seroprevalence in pregnant women in a rural area in Tanzania.

PMID- 11846720
TI  - Purification and enzymatic activity of an NADH-fumarate reductase and other
      mitochondrial activities of Leishmania parasites.
AB  - A 65 kD membrane-associated NADH-fumarate reductase subunit, which has a
      molecular weight similar to that of one of the enzyme subunits from bacteria, was
      purified from Leishmania donovani promastigotes. NADH-fumarate reductase and
      other mitochondrial enzymatic activities of L. major and L. donovani
      promastigotes and amastigotes were investigated. The presence of NADH-fumarate
      reductase was demonstrated in digitonin-permeabilized L. major promastigotes and
      mitochondria of L. major and L. donovani promastigotes and amastigotes. The
      activity of solubilized NADH-fumarate reductase was measured in L. major and L.
      donovani promastigotes. Succinate exhibited a clear concentration-dependent
      inhibitory effect on fumarate reductase, whereas fumarate also exhibited a clear
      concentration-dependent inhibitory effect on succinate dehydrogenase. The data
      indicate that fumarate reductase is an obligatory component of the respiratory
      chain of the parasite. Since the enzyme is an important component in the
      intermediate metabolism in the Leishmania parasite and is absent in mammalian
      cells, it could be a potential target for antileishmanial drugs.

PMID- 11846721
TI  - Inhibition of bacterial translocation by chronic ethanol consumption in the rat.
AB  - Chronic ethanol ingestion has been associated with small intestine morphological
      changes, disrupted host mucosal defenses and bacterial overgrowth. Since
      bacterial translocation (BT) may result from such alterations, we have
      investigated the potential effect of chronic ethanol consumption on BT. For this
      purpose, male Wistar rats were fed a liquid diet containing 5% v/v ethanol for 4
      weeks (EG, n=16), and a pair-fed group received equal daily amounts of calories
      in a similar diet without ethanol (PFG, n=16). On experimental day 29, distal
      ileum ligature and small intestine inoculation of a tetracycline-resistant E.
      coli strain (Tc E. coli R6) followed by duodenal ligature was performed. After 1
      or 5 h post inoculation, mesenteric lymph nodes, liver, spleen and kidney were
      excised. Unexpectedly, rats of the EG presented markedly less BT to the
      mesenteric lymph nodes (p<0.001) and to the other organs examined compared to
      rats of the PFG. This BT inhibition was observed at 1 and 5 h after bacterial
      inoculation, and may be attributed exclusively to chronic ethanol ingestion.
      Since alcoholism is well known to decrease host immunity, these results suggest
      that other factors, independent of the immune function, may be involved in the BT
      inhibition observed in this study.

PMID- 11846723
TI  - Complement deposition in renal allografts with early malfunction.
AB  - Among patients with early severe impairment of renal allograft function we have
      previously identified a group displaying isolated deposition of complement factor
      C3 in glomeruli. Here we studied the pattern of complement deposition more
      extensively in allograft biopsies from five patients using an immunofluorescence
      technique. We found a prominent deposition of C3c, C3d and C4d antigens in the
      glomerular capillary walls, and a positive reaction to vitronectin (S-protein),
      but only trace amounts of the complement factor C9 neoepitope. Clq, C4c, C3a,
      iC3b, factor B, properdin, immunoglobulins IgG, IgA or IgM were not found in
      glomeruli or in any other cortical structure. These findings indicate that most
      of the demonstrated glomerular C3 consists of C3b and/or C3c/C3d molecules. By
      immunoelectron microscopy the C3 antigen was found within the glomerular basement
      membrane. Our findings indicate that there is a mechanism of complement
      activation involving the early steps of the classical pathway, despite the lack
      of demonstrable immunoglobulins in the tissue. In analogy with similar reactions
      described recently in heart allografts, we suggest that this may be a
      manifestation of a humoral rejection, possibly mediated by a low titer of
      circulating antibodies directed against endothelial surface antigens, presumed to
      be the initial step leading to complement activation.

PMID- 11846722
TI  - Age- and sex-related differences in antibody responses against Schistosoma
      mansoni soluble egg antigen in a cohort of school children in Ethiopia.
AB  - Acquired immunity is believed to be the main factor in the age-related
      differences in prevalence and intensity of Schistosoma infections. We studied
      antibody responses against S. mansoni soluble egg antigen (SEA) by ELISA in
      children before treatment, 5 weeks and one year after treatment. After screening
      for S. mansoni infection, positive children were treated with praziquantel (40 mg
      per kg body weight). Infection rate was significantly higher in boys younger than
      12 years than in girls in the same age group. Levels of all antibody isotypes,
      except IgG1 (before treatment) or IgA (one year after treatment), were higher in
      children older or equal to 12 years than in those younger. The difference between
      age groups was significant for IgE, IgM, IgG3 and IgG4 (before treatment) and IgE
      (one year after treatment). Similarly, all antibody isotypes, except IgE, before
      treatment were higher in boys than in girls. At 5 weeks after treatment, IgG, IgE
      and IgG1 showed an increasing tendency, whereas IgM and IgG3 tended to decrease.
      One year after treatment, significant decreases were observed in IgG, IgG1 and
      IgG4 and a significant increase in IgG2 levels. The study presents further
      evidence for the difference in acquired immunity between younger and older
      children, and between boys and girls. The study also suggests that praziquantel
      differentially affects antibody responses against S. mansoni SEA.

PMID- 11846724
TI  - Helicobacter pylori antibodies and gastric cancer in Iceland - The decline in IgG
      antibody level is a risk factor.
AB  - H. pylori infection is considered a causal agent of duodenal ulcer and a
      significant risk factor for gastric cancer. Retrospective cohort studies have
      demonstrated a significant association between presence of antibody to H. pylori
      and gastric cancer when using samples obtained years before the diagnosis but not
      at the time of diagnosis. The present study investigates, in a population-based
      cohort, whether a decline occurs in H. pylori antibody levels before the
      diagnosis of stomach cancer. Repeat samples (2 to 5) were available from 23
      persons with gastric cancer taken up to 20 years before the diagnosis and 128
      control subjects matched for gender, age, time and number of repeat samples. The
      odds ratio of developing stomach cancer was 1.16 (95% CI 1.05-1.28) for those
      showing decline in antibody levels of 1 relative antibody activity unit per year
      versus those with constant or rising levels. We conclude that this decline in
      antibody levels in cases, and not in controls, supports an active role of H.
      pylori in the pathogenesis of gastric cancer by causing atrophic gastritis, and
      provides a better risk assessment for gastric cancer compared to single
      measurements.

PMID- 11846725
TI  - The putative R1 protein of Streptococcus agalactiae as serotype marker and target
      of protective antibodies.
AB  - The streptococcal R1 protein was studied by means of anti-R1 antibodies prepared
      by appropriate cross-absorption of rabbit antiserum raised against the group B
      streptococcal (GBS) strain ATCC 12403 (D136C), serotype III/R1. The protein was a
      ladder-forming antigen according to banding patterns in immunoblotting, similar
      to several other GBS proteins, and was susceptible to digestion by both pepsin
      and trypsin. Antibody-based testing revealed that 10% of Norwegian GBS isolates
      expressed the R1 protein, most frequently capsular antigen type V strains (72%)
      and less frequently type III strains (3%). None of 132 GBS strains from Zimbabwe,
      including 39 type V strains, expressed the R1 protein. R1-specific rabbit
      antibodies showed protective activity in mice challenged with a GBS type V/R1
      strain. The results show that the R1 protein is an important GBS serotype marker
      in strains from certain geographical areas, notably for the subtyping of capsular
      type V strains, and that this protein is a target of protective antibodies.

PMID- 11846726
TI  - Human lung microvascular endothelial cells activate allogeneic T cells through an
      LFA-3-dependent, but CD86-independent mechanism.
AB  - To date, immunosuppressive therapy for allograft rejection is based on a
      generalized inhibition of the recipient's T cells, rendering the individual less
      resistant to infections and malignancies. In order to change this therapeutic
      approach towards the induction of specific transplant tolerance, it is essential
      to identify the cells and molecular pathways involved in direct allorecognition.
      An in vitro model with interferon-gamma (IFN-gamma)-stimulated human lung
      microvascular endothelial cells (HMVEC-L) as targets and allogenic T cells as
      responders was used to identify donor cells for recipient cellular
      immunorecognition. HMVEC-L activated purified allogenic T cells in cocultures.
      This activation was partly mediated by lymphocyte function antigen-3 (LFA-3), but
      not CD86, as shown by monoclonal antibody (mAb) inhibition. This finding was
      supported by the expression of LFA-3 antigen, but not CD86, on IFN-gamma
      stimulated HMVEC-L. Surprisingly, even in the absence of T-cell proliferation, T
      cells were capable of enhancing LFA-3 antigen, but not CD86 expression on HMVEC
      L. In conclusion, HMVEC-L are capable of direct allostimulation of human T cells,
      partly through an LFA-3-dependent costimulatory pathway. Since ICAM-1 expression
      on HMVEC is greatly enhanced by IFN-gamma and T cell coculturing, this molecule
      may serve as an additional costimulator. A reciprocal HMVEC-L stimulation by
      allogenic T-cells occurs, even without T-cell proliferation, possibly
      representing a preproliferative phase. Since this study included a single target
      as well as responder cell donor, further studies with multiple donors are needed
      to evaluate possible variations.

PMID- 11846727
TI  - Application of molecular biology techniques to the diagnosis of nontuberculous
      mycobacterial infections.
AB  - A total of 19,723 clinical samples were cultivated for the detection of
      mycobacteria from January 1995 to March 2001. The 203 strains of nontuberculous
      mycobacteria isolated were identified with the use of molecular techniques in
      combination with traditional biochemical tests. The molecular methods applied
      were PCR-restriction fragment length polymorphism analysis (PRA) alone or in
      combination with 16S rRNA and 16S-23S spacer sequencing. The patient records of
      those with specimens positive for mycobacteria were analysed to evaluate the
      clinical significance of the culture results. Twenty-five of the 124 patients
      analysed (20%) were regarded as having clinical mycobacteriosis. The main species
      associated with mycobacteriosis were: Mycobacterium avium (13 cases), M.
      intracellulare (2 cases), M. kansasii (5 cases), M. chelonae (2 cases), M.
      malmoense (1 case), M. scrofulaceum (1 case) and M. marinum (1 case). The use of
      PRA alone or in combination with gene sequencing provided valuable help in
      discerning mycobacteria at both the intra- and interspecies level, thus
      contributing to a faster and more efficient diagnosis and epidemiological follow
      up.

PMID- 11846728
TI  - Proliferative activity in human glioblastomas assessed by various techniques.
AB  - Determination of proliferative activity in tumours may be valuable in diagnosis
      and prognosis. In this study, commonly used proliferation markers were
      investigated and compared in 12 cases of human glioblastoma. Paraffin sections
      were incubated with four commercial Ki67-equivalent antibodies, anti-PCNA, and
      anti-bcl-2. S-phase fraction and mitotic activity were determined as well. The
      different Ki67 antibodies gave satisfactory immunostainings, though they provided
      a wide range of proliferation indices (PI) intra- and intertumorally.
      Correlations between the Ki67 antibodies and the other proliferation markers
      were, broadly speaking, poor. PCNA immunostaining was hampered by disturbing
      background staining. Few bcl-2-immunoreactive cells were observed, mainly
      gemistocytes. Flow cytometric analyses provided reliable S-phase fraction values,
      and two aneuploid tumours were detected. The mitotic activity was generally high.
      Thus, mitotic counting remains a convenient method for assessing proliferative
      activity in astrocytic tumours. Ki67 antibodies are important alternatives, for
      instance in stereotactic brain biopsies. Under all circumstances, proliferation
      markers should be used in combination with established histopathological criteria
      for malignancy in these tumours.

PMID- 11846729
TI  - EGFR and p53 expression and proliferative activity in parathyroid adenomas; an
      immunohistochemical study.
AB  - EGFR (epidermal growth factor receptor), p53, and proliferative markers provide
      some clues as to the formation of several tumours. In this study the mechanism of
      the genesis of parathyroid adenomas was investigated using immunohistochemistry.
      Sections of parathyroid adenomas from 12 cases were stained using PCNA
      (proliferating cell nuclear antigen), EGFR, and p53 immunohistochemistry.
      Correlations between PCNA LI (labelling index), EGFR expression, p53 expression,
      age, serum parathormone, Ca and P levels, and tumour diameter were investigated.
      PCNA LI was 45.8+/-33.1 (mean+/-standard deviation) and all the cases were
      somewhat positive. Five cases (41.67 %) were EGFR positive. Maximum 10 % of the
      cells were positive in these cases. All the cases were p53 negative. There was a
      correlation between PCNA LI and serum parathormone level (r=0.607, p=0.036).
      According to these results, parathormone synthesis is high when the proliferative
      activity of parathyroid adenoma is high. Four of the five EGFR-positive patients
      were below 35 years of age. These data may indicate that formation of parathyroid
      adenoma in young patients is related to a mechanism involving EGFR. Absence of
      p53 expression suggests that p53 mutation is not a common component of
      parathyroid adenomas.

PMID- 11846730
TI  - Intranodal benign thyroid tissue: significance of HBME-1 in differentiation from
      metastatic papillary thyroid carcinoma.
AB  - The aim of this study was to determine the significance of HBME-1 immunostaining
      in the differentiation between intranodal benign thyroid tissue and metastatic
      papillary thyroid carcinoma in the lymph node. Immunohistochemically we examined
      normal-appearing intranodal thyroid tissue in four patients who did not show
      evidence of papillary carcinoma histologically or clinically. We also examined
      follicular-pattern-predominant papillary carcinoma with metastatic foci in the
      lymph nodes. Normal-appearing intranodal thyroid tissue and normal thyroid showed
      no immunopositivity for HBME-1. In contrast, all papillary carcinomas in both the
      lymph nodes and thyroid demonstrated strong positivity for HBME-1. HBME-1 was
      predominantly positive for the luminal surface of the tumor cells. The
      immunopositivity of the cuboidal and low columnar carcinoma cells was more
      intensive than that of the flat-shaped cells in the lymph nodes and thyroid. The
      results probably indicate that HBME-1 immunostaining is helpful in distinguishing
      between intranodal benign thyroid tissue and metastatic papillary carcinoma in
      lymph nodes. We emphasize that the HBME-1 reactivity should be evaluated in
      connection with the histological findings, and that positive and negative
      controls stained in parallel are necessary.

PMID- 11846731
TI  - The fragile X gene and its function.
AB  - The fragile X syndrome represents the most common inherited cause of mental
      retardation worldwide. It is caused by a stretch of CGG repeats within the
      fragile X gene, which increases in length as it is transmitted from generation to
      generation. Once the repeat exceeds a threshold length, no protein is produced
      resulting in the fragile X phenotype. Ten years after the discovery of the gene,
      much has been learned about the function of the fragile X protein. Knowledge has
      been collected about the mutation mechanism, although still not all players that
      allow the destabilization of the CGG repeat are known.

PMID- 11846732
TI  - When body segmentation goes wrong.
AB  - The segmented or metameric aspect is a basic characteristic of many animal
      species ranging from invertebrates to man. Body segmentation usually corresponds
      to a repetition, along the anteroposterior (AP) axis, of similar structures
      consisting of derivatives from the three embryonic germ layers. In humans,
      segmentation is most obvious at the level of the vertebral column and its
      associated muscles, and also in the peripheral nervous system (PNS).
      Functionally, segmentation is critical to ensure the movements of a rod-like
      structure, such as the vertebral column. The segmented distribution of the
      vertebrae derives from the earlier metameric pattern of the embryonic somites.
      Recent evidence from work performed in fish, chick and mouse embryos indicates
      that segmentation of the embryonic body relies on a molecular oscillator called
      the segmentation clock, which requires Notch signaling for its proper
      functioning. In humans, mutations in genes required for oscillation, such as
      Delta-like 3 (DLL3), result in abnormal segmentation of the vertebral column, as
      found in spondylocostal dysostosis syndrome, suggesting that the segmentation
      clock also acts during human embryonic development.

PMID- 11846733
TI  - History of genetics through philately - deafness.

PMID- 11846734
TI  - A family with a grand-maternally derived interstitial duplication of proximal
      15q.
AB  - About 1% of individuals with autism or types of pervasive developmental disorder
      have a duplication of the 15q11-q13 region. These abnormalities can be detected
      by routine G-banded chromosome study, showing an extra marker chromosome, or
      demonstrated by fluorescence in situ hybridization (FISH) analysis, revealing an
      interstitial duplication. We report here the molecular, cytogenetic, clinical and
      neuropsychiatric evaluations of a family in whom 3 of 4 siblings inherited an
      interstitial duplication of 15q11-q13. This duplication was inherited from their
      mother who also had a maternally derived duplication. Affected family members had
      apraxia of speech, phonological awareness deficits, developmental language
      disorder, dyslexia, as well as limb apraxia but did not have any dysmorphic
      clinical features. The observations in this family suggest that the phenotypic
      manifestations of proximal 15q duplications may also involve language-based
      learning disabilities.

PMID- 11846736
TI  - To test or not to test: an ethical conflict with presymptomatic testing of
      individuals at 25% risk for Huntington's disorder.
AB  - The first presymptomatic test for Huntington's disease was developed in the
      1980s. With the detection of the gene causing the disorder in 1993, it became
      possible to do direct mutation tests with almost 100% sensitivity and
      specificity. The author discusses some of the ethical issues that arise when an
      adult child at 25% risk for the disease wishes to have the test, but the
      parent(s) at 50% risk refuses to have one. If the child tests positive, the
      genetic status of the parent will also be disclosed. No matter what course of
      action is chosen in this situation, the ethically legitimate interests of either
      child or parent might be violated. The author examines different alternatives and
      suggests a solution that might be acceptable to all parties.

PMID- 11846735
TI  - Distribution of alpha1-antitrypsin PI S and PI Z frequencies in countries outside
      Europe: a meta-analysis.
AB  - The objective of the present study was to review published surveys on allelic
      frequencies S and Z in countries outside Europe to evaluate the validity of the
      reported data. Studies on the topic, published from 1965 to May 2001, were
      retrieved using MEDLINE and bibliographic reference consultations. The criteria
      for the selection of the studies were the following: 1) sample size >or=250
      individuals; 2) alpha1-antitrypsin phenotype determination performed by means of
      crossed antigen-antibody, isoelectric focusing in polyacrylamide gels, or
      polymerase chain reaction (PCR); 3) PI type determination performed without any
      previous screening procedure; 4) S and Z 95% CI of the reported outcomes within
      the limits of a calculated coefficient of variation. Forty-three out of 85
      studies comply with the established criteria for being analysed. Worldwide maps
      of geographical distributions of PI S and PI Z frequencies have been designed by
      the authors by adding the data provided by these 43 selected studies to the 70
      reported in a recent European meta-analysis.

PMID- 11846737
TI  - Mutations of the NOG gene in individuals with proximal symphalangism and multiple
      synostosis syndrome.
AB  - Proximal symphalangism is an autosomal-dominant disorder with ankylosis of the
      proximal interphalangeal joints, carpal and tarsal bone fusion, and conductive
      deafness. These symptoms are shared by another disorder of joint morphogenesis,
      multiple synostoses syndrome. Recently, it was reported that both disorders were
      caused by heterozygous mutations of the human noggin gene (NOG). To date, seven
      mutations of NOG have been identified from unrelated families affected with joint
      morphogenesis. To characterize the molecular lesions of proximal symphalangism,
      we performed analyses of NOG in three Japanese individuals with proximal
      symphalangism. We found three novel mutations: g.551G>A (C184Y) in a sporadic
      case of symphalangism, g.386T>A (L129X) in a familial case of symphalangism, and
      a g.58delC (frameshift) in a family with multiple synostosis syndrome.
      Characteristic genotype-phenotype correlations have not been recognized from the
      mutations in the NOG gene.

PMID- 11846738
TI  - Frequency of the 35delG mutation in the connexin 26 gene in Turkish hearing
      impaired patients.
AB  - The 35delG mutation in the connexin 26 gene (GJB2) at the DFNB1 locus is the most
      common mutation in patients with autosomal-recessive sensorineural deafness.
      Genetic diagnosis is crucial for genetic counseling. We have developed an easy
      and simple method and screened a total of 235 unrelated hearing-impaired
      children. We found 48 of the subjects to be homozygous for the mutation,
      including 27 of 83 familial cases, 15 of 101 singletons, 4 of 9 subjects born to
      assortative marriages (deaf married to deaf), and 2 of 42 subjects for whom the
      parents claimed an environmental factor as the etiology of the condition. The
      high ratio of individuals homozygous for the mutation indicated that the 35delG
      mutation in the connexin gene accounts for more than 90% of the mutations at this
      locus.

PMID- 11846739
TI  - Familial Down syndrome: evidence supporting cytoplasmic inheritance.
AB  - The frequently observed familial aggregation of Down syndrome (DS) 47,+21 and
      other aneuploidies and the phenomenon of double aneuploidy involving DS cannot be
      accounted for by chance alone. To clarify possible aetiological factors,
      pedigrees from all 7 affected families with repeated marriages referred to two
      regional genetics centres were examined. In each case the recurrence of
      aneuploidy was on the mother's side (p<0.01). Such a pattern suggests cytoplasmic
      inheritance of a risk factor. The hypothesis that mitochondrial DNA mutations
      have a role in the aetiology of DS is supported by other observations as well as
      by theoretical considerations.

PMID- 11846741
TI  - Founder mutations in the BRCA1 gene in west Belarusian breast-ovarian cancer
      families.

PMID- 11846740
TI  - A logistic regression model for measuring gene-longevity associations.
AB  - The logistic regression model is a popular model for data analysis in
      epidemiological research. In this paper, we use this model to analyze genetic
      data collected from gene-longevity association studies. This new approach models
      the probability of observing one genotype as a function of the age of
      investigated individuals. Applying the model to genotype data on the TH and
      3'ApoB-VNTR loci collected from an Italian centenarian study, we show how it can
      be used to model the different ways that genes affect survival, including sex-
      and age-specific influences. We highlight the advantages of this application over
      other available models. The application of the model to empirical data indicates
      that it is an efficient and easily applicable approach for determining the
      influences of genes on human longevity.

PMID- 11846742
TI  - Pyruvate kinase deficiency: prevalence of the 1456C-->T mutation in the
      Portuguese population.

PMID- 11846743
TI  - Vietnamese sisters with Grebe syndrome on a TV program in Japan.

PMID- 11846744
TI  - Mutation in the connexin 50 gene (GJA8) in a Russian family with zonular
      pulverulent cataract.

PMID- 11846745
TI  - A systematic search for single nucleotide polymorphisms (SNPs) in the insulin
      receptor gene: association of an SNP with hyperlipidemia in Japanese type 2
      diabetic subjects.

PMID- 11846746
TI  - Guidelines for performing skin tests with drugs in the investigation of cutaneous
      adverse drug reactions.
AB  - Skin testing with a suspected drug has been reported to be helpful in determining
      the cause of cutaneous adverse drug reactions (CADR). Many isolated reports of
      positive drug skin tests are published, but without detailed information
      concerning the clinical features of the CADR and the method used in performing
      drug skin tests, such data are not very informative. A working party of the
      European Society of Contact Dermatitis (ESCD) for the study of skin testing in
      investigating cutaneous adverse drug reactions, has proposed the herein-reported
      guidelines for performing skin testing in CADR in order to standardize these
      procedures. In each reported case, the imputability of each drug taken at the
      onset of the CADR and a highly detailed description and characterization of the
      dermatitis need to be given. Drug skin tests are performed 6 weeks to 6 months
      after complete healing of the CADR. Drug patch tests are performed according to
      the methods used in patch testing in studying contact dermatitis. The
      commercialized form of the drug used by the patient is tested diluted at 30% pet.
      (pet.) and/or water (aq.). The pure drug is tested diluted at 10% in pet. or aq.
      In severe CADR, drug patch tests are performed at lower concentrations. It is
      also of value to test on the most affected site of the initial CADR. Drug prick
      tests are performed on the volar forearm skin with the commercialized form of the
      drug, but with sequential dilutions in cases of urticaria. Intradermal tests
      (IDT) are performed with sterile sequential dilutions (10-4, 10-3, 10-2, 10-1) of
      a pure sterile or an injectable form of the suspected drug with a small volume of
      0.04 ml. Drug skin tests need to be read at 20 min and also later at D2 and D4
      for patch tests, at D1 for prick tests and IDT. All these tests also need to be
      read at 1 week. The success of skin tests varies with the drug tested, with a
      high % of positive results, for example, with betalactam antibiotics,
      pristinamycin, carbamazepine and tetrazepam on patch testing, or with betalactam
      antibiotics and heparins on delayed readings of IDT. The results of drug skin
      tests also depend on the clinical features of the CADR. The use of appropriate
      control patients is necessary to avoid false-positive results.

PMID- 11846747
TI  - Evaluation of the Skin and Cancer Foundation standard series in the diagnosis of
      allergic contact dermatitis.
AB  - The use of a standard series of 37 allergens was evaluated in a retrospective
      study of 817 consecutive patients seen between April 1988 and January 1993 at the
      Skin and Cancer Foundation, Melbourne, Australia. Of the 316 patients with
      clinically relevant patch test results, 134 (42%) reacted to an allergen in the
      standard series alone, while an additional 122 (39%) had reactions to allergens
      in both the standard and supplementary series. The remaining 60 (19%) patients
      reacted only to allergens in the supplementary series. These data suggest that
      the use of our standard series alone will detect about 80% of allergic contact
      dermatitis cases, but that many of these may be insufficiently evaluated. Use of
      supplementary allergen testing in a specialised clinic is recommended for
      patients who may have allergic contact dermatitis.

PMID- 11846748
TI  - Understanding fragrance allergy using an exposure-based risk assessment approach.
AB  - Conducting a sound skin sensitization risk assessment prior to the introduction
      of new ingredients and products into the market place is essential. The process
      by which low-molecular-weight chemicals induce and elicit skin sensitization is
      dependent on many factors, including the ability of the chemical to penetrate the
      skin, react with protein, and trigger a cell-mediated immune response. Based on
      our chemical, cellular and molecular understanding of allergic contact
      dermatitis, it is possible to carry out a quantitative risk assessment.
      Specifically, by estimating the exposure to the allergen and its allergenic
      potency, it is feasible to assess quantitatively the sensitization risk of an
      ingredient in a particular product type. This paper focuses on applying exposure
      based risk assessment tools to understanding fragrance allergy for 2 hypothetical
      products containing the fragrance allergen cinnamic aldehyde. The risk assessment
      process predicts that an eau de toilette leave-on product containing 1000 ppm or
      more cinnamic aldehyde would pose an unacceptable risk of induction of skin
      sensitization, while a shampoo, containing the same level of cinnamic aldehyde,
      would pose an acceptable risk of induction of skin sensitization, based on
      limited exposure to the ingredient from a rinse-off product application.

PMID- 11846749
TI  - Self-diagnosed dermatitis in adults. Results from a population survey in
      Stockholm.
AB  - In a population-based survey of public health issues in Stockholm, Sweden, self
      reported hand eczema, history of childhood eczema, nickel allergy, occurrence of
      skin symptoms on the face and intolerance to cosmetics and hygiene products, were
      investigated. A postal questionnaire was sent to 15,000 inhabitants aged 19-80
      years. The response rate was 73%. The 1-year prevalence of hand eczema was 8%
      (females 10%, males 6%). History of childhood eczema was reported by 15% and, of
      these, 42% also stated positively that they had had hand eczema at some time.
      Hypersensitivity to nickel was owned to 15% of the females and 3% of the males.
      Of the nickel-sensitive, 30% reported ever having had hand eczema. The
      combination of nickel allergy and history of childhood eczema resulted in a
      cumulative prevalence of hand eczema of 56%. Females reported more hand-washings
      per day than did males, and a relation between number of hand-washings and hand
      eczema was found. Self-reported 1-year prevalence of skin symptoms on the face
      was 14% and, of these, 33% also owned to hypersensitivity to cosmetics.
      Dermatitis appears to be a common health problem. This fact should be made clear
      to those who give priority and allocate resources to health problems, e.g., by
      participation of dermatologists in performing population-based surveys.

PMID- 11846750
TI  - Ethnic variation in the skin irritation response.
AB  - There is a widespread, but largely unsubstantiated, view that certain skin types
      may be more susceptible to the effect of skin irritants than others. One
      expression of this would be that certain ethnic groups may also be more likely to
      experience skin irritation. As a consequence, when evaluating the skin
      compatibility of substances/preparations, these differences may need to be taken
      into account. However, other evidence indicates that, within any particular
      group, inter-individual variation is likely to be much larger than the
      differences between means for distinct groups. In this study, we have
      investigated 2 carefully matched panels of Caucasian and Japanese women
      volunteers to determine their topical irritant reaction, both acute and
      cumulative, to a range of materials. The results indicated that the acute
      irritant response tended to be greater in the Japanese panel and this reached
      statistical significance with the stronger irritants. Cumulative irritation was
      investigated only with the weaker irritants and, although again the trend was to
      a higher response in Japanese compared to Caucasian panelists, this rarely
      reached significance. Nevertheless, where risk assessment for skin irritation was
      critical, then at the population level, these differences might be relevant, both
      for safety in use of substances and products and for skin acceptability.

PMID- 11846751
TI  - Persistence of contact allergy among Danish adults: an 8-year follow-up study.
AB  - In 1990, a random sample of 567 persons of the 15-69-year-old population living
      in the Western part of Copenhagen County, Denmark, was patch tested in a cross
      sectional study. In 1998, a follow-up study was performed. Out of 540 invited,
      365 (68%) were re-patch tested. In the follow-up study, the persistence of
      allergic contact sensitivity, defined as 1 or more positive patch tests in both
      surveys, was 71% (37 out of 52 subjects). Nickel allergy persisted in 79% (19 out
      of 24 subjects), while 60% (21 out of 35 subjects) had a positive patch test
      reaction to 1 or more allergens, other than nickel, in both surveys. The lowest
      persistence was 50% (5 out of 10 subjects) and this was found for patch test
      reactivity to 1 or more of the cosmetic ingredients included in the patch test
      series. 8 years after the baseline study had demonstrated allergic contact
      sensitivity, 71% of the subjects still had at least 1 positive patch test. Nickel
      allergy persisted in 79%. Allergen avoidance should probably be lifelong to
      prevent elicitation of contact dermatitis.

PMID- 11846752
TI  - Occupational protein contact dermatitis from coriander.

PMID- 11846753
TI  - Allergic contact dermatitis from laureth-9 and polyquaternium-7 in a skin-care
      product.

PMID- 11846754
TI  - Allergic contact dermatitis from local anaesthetic on peristomal skin.

PMID- 11846755
TI  - Contact anaphylaxis due to para-aminophenol and para-methylaminophenol in hair
      dye.

PMID- 11846756
TI  - An epidemic of allergic contact dermatitis from epilating products.

PMID- 11846757
TI  - A spontaneous mutant of microcystin biosynthesis: genetic characterization and
      effect on Daphnia.
AB  - Microcystis aeruginosa strain MRC is unique in its' possession of the mcyA-J gene
      cluster, which encodes microcystin synthetase, but its' inability to produce
      microcystins. M. aeruginosa strain MRD is genetically identical to MRC at
      numerous genomic loci examined, but produces a variety of microcystins, mainly
      with the amino acid tyrosine in the molecule. Zooplankton studies with Daphnia
      galeata and D. pulicaria, using the mutant (MRC) and its' wild type (MRD), showed
      for the first time that microcystins other than microcystin-LR can be responsible
      for the poisoning of Daphnia by Microcystis. Regardless of microcystin content,
      both Daphnia exhibited significantly reduced ingestion rates when fed with either
      strain of M. aeruginosa compared with the green alga Scenedesmus acutus. A
      disruption of the molting process in both Daphnia spp. was noted when these
      species were fed with MRC cells. Such symptoms on Daphnia have not been
      previously reported for cyanobacteria and may point to a bioactive compound,
      other than microcystin, which inhibits the hardening of protein-chitin complexes
      in Daphnia.

PMID- 11846758
TI  - Contrasting bacterioplankton community composition and seasonal dynamics in two
      neighbouring hypertrophic freshwater lakes.
AB  - We characterized the bacterioplankton community and its seasonal dynamics in two
      neighbouring hypertrophic lakes by denaturing gradient gel electrophoresis (DGGE)
      analysis of short (193 bp) 16S ribosomal DNA polymerase chain reaction (PCR)
      products obtained with primers specific for the domain Bacteria. Lake Blankaart
      is turbid and has a high phytoplankton biomass and episodic cyanobacterial
      blooms, whereas biomanipulated Lake Visvijver is characterized by clearwater
      conditions and the establishment of a dense charophyte vegetation. Both lakes
      were dominated by bacterial groups commonly found in freshwater habitats (e.g.
      ACK4 cluster of Actinomycetes; ACK stands for clones isolated from the Adirondack
      mountain lakes). Yet, cluster analysis and principal components analysis (PCA)
      revealed that taxon composition of the bacterioplankton community of the two
      lakes differs substantially and consistently throughout the season. During the
      study year (1998), the bacterioplankton community of both lakes showed a distinct
      seasonal pattern. Lake Blankaart showed a clear differentiation between winter,
      spring, summer and autumn. In Lake Visvijver, summer samples differed greatly
      from spring, autumn and winter samples. We hypothesize that the contrasting
      bacterioplankton in the two neighbouring shallow lakes is determined largely by
      the presence or absence of macrophytes.

PMID- 11846759
TI  - Characterization of nickel-resistant bacteria isolated from serpentine soil.
AB  - In the present study, heterotrophic nickel-resistant bacteria were isolated and
      characterized from three different serpentine outcrops in central Italy populated
      by the nickel-hyperaccumulating plant Alyssum bertolonii. Bacteria were isolated
      from the rhizosphere of the plant and from soil portions at various distances
      from the plant. The proportion of nickel-resistant cfu was higher in proximity to
      the plant than in free soil. A total of 138 isolates was collected and grouped
      into 47 different operational taxonomic units (OTUs) by means of amplified
      ribosomal DNA restriction analysis (ARDRA) and into 25 heavy-metal resistant
      phenotypes. The phylogenetic position of strains belonging to 20 OTUs,
      representing more than the 70% of the total isolates, was determined by 16S rDNA
      sequencing. These analyses showed that the most represented genera in all three
      different outcrops were Pseudomonas and Streptomyces. Pseudomonas strains were
      found to be predominant in the plant rhizosphere, whereas Streptomyces strains
      were mainly present in the soil.

PMID- 11846760
TI  - Identification of a microorganism that links its growth to the reductive
      dechlorination of 2,3,5,6-chlorobiphenyl.
AB  - Anaerobic bacteria reductively dechlorinate polychlorinated biphenyls (PCBs) in
      aquatic sediments, but these microorganisms remain uncultured and, until now,
      unidentified. Through denaturing gradient gel electrophoresis (DGGE) of 16S rDNA
      from a highly enriched ortho-PCB dechlorinating culture, the growth of a single
      microorganism was shown to be dependent upon the presence and dechlorination of
      2,3,5,6-tetrachlorobiphenyl. This is the first identification of a microorganism
      that catalyses the reductive dechlorination of a PCB. The organism, bacterium o
      17, has high sequence similarity with the green non-sulphur bacteria and with a
      group that includes Dehalococcoides ethenogenes. Bacterium o-17 required acetate
      for dechlorination and growth. H2:CO2 (80:20 at 101 kPa) did not support
      dechlorination or growth of the dechlorinator. Archaeal 16S rDNA was not detected
      in actively dechlorinating bromoethanesulphonate-treated non-methanogenic
      cultures, which indicated that methanogenic Archaea were not required for
      dechlorination. The consistent association with dechlorinating activity combined
      with high similarity to other known dechlorinating microorganisms indicates that
      bacterium o-17 catalyses the reductive ortho-dechlorination of 2,3,5,6
      tetrachlorobiphenyl.

PMID- 11846761
TI  - Comparative analysis of polychlorinated biphenyl-dechlorinating communities in
      enrichment cultures using three different molecular screening techniques.
AB  - The catalysts for many microbially mediated environmental processes such as the
      dechlorination of polychlorinated biphenyls (PCBs) have been difficult to
      identify by traditional isolation techniques. Numerous, as yet unsuccessful,
      attempts have been made to isolate and culture the dechlorinating species. To
      overcome this limitation, amplified rDNA restriction analysis (ARDRA) of a clone
      library, denaturing gradient gel electrophoresis (DGGE) and terminal restriction
      fragment length polymorphism (TRFLP) were used concurrently to compare their
      effectiveness for characterizing an enriched microbial community. These methods
      were applied to enrichment cultures that selectively dechlorinated double-flanked
      chlorines in the PCB congener 2,3,4,5 chlorinated biphenyl. The methods have
      different biases, which were apparent from discrepancies in the relative clone
      frequencies (ARDRA), band intensities (DGGE) or peak heights (TRFLP) from the
      same enrichment culture. However, each method was effectively qualitative and
      identified the same organisms: a low G + C Gram-positive eubacterium, an organism
      most similar to the green non-sulphur bacteria, an Aminobacterium sp. and a
      Desulfovibrio sp. Overall, in community fingerprinting and preliminary
      identification, DGGE proved to be the most rapid and effective tool for the
      monitoring of microorganisms within a highly enriched culture. TRFLP results
      corroborated DGGE fingerprint analysis; however, identification required the
      additional step of creating a clone library. ARDRA provided an in-depth analysis
      of the community and this technique detected slight intraspecies sequence
      variation in 16S rDNA. These molecular methods are common in environmental
      microbiology, but rarely are they compared with the same sample site or culture.
      In general, all three methods detected similar community profiles, but inherent
      biases resulted in different detection limits for individual OTUs (operational
      taxonomic units).

PMID- 11846762
TI  - Biomonitoring of pJP4-carrying Pseudomonas chlororaphis with Trb protein-specific
      antisera.
AB  - The transfer of catabolic genes on conjugative plasmids to indigenous organisms
      from which they may spread further into the community allows the introduction of
      new biodegradative pathways for metabolic conversion of pollutants to the
      community. Biomonitoring of IncP plasmid pJP4-carrying Pseudomonas chlororaphis
      from the rhizosphere of Arabidopsis thaliana was achieved using antisera specific
      for proteins from the plasmid transfer machinery. Antisera were generated that
      recognized TrbC and TrbF, the putative major and minor components of pJP4
      determined pili, respectively, and the putative lipoprotein TrbH. Cell
      fractionation studies showed association of TrbC, TrbF and TrbH with the cells
      and suggested that TrbC and TrbF are part of extracellular pJP4-determined pili.
      TrbF and TrbH antisera allowed specific detection of IncP compared with IncN or
      IncW plasmid-carrying cells and even permitted differentiation between bacteria
      carrying IncPalpha plasmid RP4 and IncPbeta plasmid pJP4. Immunofluorescence
      microscopy was applied to detect TrbF and TrbH signal at the cell periphery,
      allowing distinction from autofluorescing cells and soil debris. In situ
      experiments showed specific recognition of pJP4-carrying cells from laboratory
      cultures, as well as from the rhizosphere of A. thaliana grown in natural soil.
      After co-inoculation of donor P. chlororaphis pJP4 and recipient Ralstonia
      eutropha, a combination of immunofluorescence and oligonucleotide hybridization
      techniques permitted the detection of plasmid transfer between both organisms in
      the A. thaliana rhizosphere. This strategy may be generally applicable for the
      analysis of plasmid transfer in natural ecosystems.

PMID- 11846763
TI  - Inhibition of biofilm formation and swarming of Escherichia coli by (5Z)-4-bromo
      5-(bromomethylene)-3-butyl-2(5H)-furanone.
AB  - The quorum-sensing disrupter (5Z)-4-bromo-5-(bromomethylene)-3-butyl-2(5H)
      furanone (furanone) of the alga Delisea pulchra was found to inhibit the swarming
      motility of Escherichia coli completely at 13 microg cm-2 (also at 20 microg ml
      1) but did not inhibit its growth rate at 13-52 microg cm-2 or from 20 to 100
      microg ml-1. Swimming was not inhibited by the furanone at 20-40 microg ml-1. In
      addition, confocal scanning laser microscopy revealed that this furanone at 60
      microg ml-1 inhibited the biofilm formation of E. coli, as it decreased its
      thickness by 55%, reduced the number of water channels and decreased the
      percentage of live cells by 87%. This suggests that natural furanone may be used
      as a new method to control bacterial biofilms that does not involve toxicity.
      Furanone at 10 microg ml-1 also inhibited by 3300-fold the quorum sensing of
      Vibrio harveyi via autoinducer 1 (AI-1) and inhibited by 5500-fold that of V.
      harveyi via of autoinducer 2 (AI-2) as well as inhibited by 26-600-fold the
      quorum sensing of E. coli via AI-2; hence, this furanone is a non-specific
      intercellular signal antagonist.

PMID- 11846767
TI  - Biological land mines: bioterrorism underscores major knowledge deficits in the
      ecology of infectious agents.

PMID- 11846768
TI  - Osmoadaptation in bacteria and archaea: common principles and differences.
AB  - The availability of water is the most important prerequisite for life of any
      living cell, and exposure of cells to hypersaline conditions always threatens the
      cells with a drastic loss of water. To re-establish the essential turgor
      pressure, cells increase the water activity of their cytoplasm by accumulation of
      compatible solutes, either by synthesis or by uptake. The ability to respond to
      increasing osmolality is well conserved in all three lines of descent and, here,
      we compare the osmoadaptive strategies of Bacteria and Archaea. The temporal
      sequence of events after an osmotic upshock will be discussed, with a focus on
      the most rapid response, notably the mechanisms of transport activation at the
      protein level, and different signals for osmolality will be compared. The
      spectrum of compatible solutes used by different organisms is rather diverse and
      a comparison of 'bacterial' and 'archaeal' compatible solutes will be given.

PMID- 11846769
TI  - The probiotic potential against vibriosis of the indigenous microflora of rainbow
      trout.
AB  - The antibacterial properties of the indigenous microflora of rainbow trout
      (Oncorhynchus mykiss Walbaum) and the potential use of inhibitory bacteria as
      fish probiotics were investigated. A total of 1018 bacteria and yeasts were
      isolated on tryptone soy agar (TSA) from skin, gills and intestine. Forty-five of
      these inhibited growth of the fish pathogenic bacterium Vibrio anguillarum in a
      well diffusion assay. The antagonism was most prominent among Pseudomonas spp.,
      as 28 (66%) of the antagonistic bacteria belonged to this genus, despite
      constituting only 15% of the total tested flora. As pseudomonads are typically
      siderophore producers, chrome azurol S (CAS) agar was used as a semi-selective
      medium for isolation of antagonistic bacteria. On this medium, 75% of the iron
      chelating strains were inhibitory to V. anguillarum. Eight strains out of a
      subset of 11 antagonists caused a 3-6 log unit reduction in the density of V.
      anguillarum [measured by polymerase chain reaction (PCR) detection in a most
      probable number (MPN) regimen] in a broth co-culture assay. Survival of rainbow
      trout infected with vibriosis was improved 13-43% by six out of nine antagonistic
      strains tested in vivo. All disease-protecting strains were pseudomonads,
      isolated from CAS plates, whereas two Carnobacterium spp. that were antagonistic
      in in vitro well diffusion assays did not alter the accumulated mortality of
      rainbow trout. The addition of live bacterial cultures to fish-rearing water may
      thus improve survival of the fish; however, in vitro antagonism could not
      completely predict an in vivo effect. Further studies on the underlying mechanism
      of activity are required to design appropriate selection criteria for fish
      probiotic bacteria.

PMID- 11846770
TI  - Detection and activity of insertion sequences in environmental strains of
      Burkholderia.
AB  - The presence of two insertion sequences, IS406 and IS407, was tested by
      polymerase chain reaction (PCR) amplification in 25 strains representing 15
      Burkholderia species and the close relative Ralstonia pickettii. A total of 50%
      of the 25 strains contained at least one of the two insertion sequences (ISs) and
      a statistically significant correlation was found between the occurrences of
      IS406 and IS407. Moreover, PCR-RFLP studies of the amplified fragments showed
      that IS406 is largely conserved among all the strains tested, whereas IS407 is
      rather polymorphic. Transposition activity was studied in Burkholderia
      vietnamiensis TVV75, using the pGBG1 target plasmid. This entrapping plasmid
      permitted the isolation and characterization of three active IS, able to activate
      the plasmid-borne tetA gene after transposition. Sequencing permitted the
      identification of these mobile genetic elements as isoforms of IS402, IS407 and
      IS1416. PCR amplification products provided IS probes, which were used to
      determine the copy-numbers of IS402, IS407 and IS1416 in the genome of B.
      vietnamiensis TVV75, by Southern blotting. Copy numbers are 12, 3 and 11
      respectively. To our knowledge, this is the first description of active insertion
      sequences in B. vietnamiensis.

PMID- 11846771
TI  - Structure and carbohydrate analysis of the exopolysaccharide capsule of
      Pseudomonas putida G7.
AB  - The aromatic hydrocarbon-degrading bacterium, Pseudomonas putida G7, produces
      exopolymers of potential interest in biotechnological applications. These
      exopolymers have been shown to have significant metal-binding ability. To
      initiate the study of the metal-polymer interactions, we explored the physical
      and chemical nature of the P. putida G7 exopolysaccharide, a major component of
      the exopolymer. A capsular structure was observed by light microscopy surrounding
      both planktonic and attached cells in biofilms after immunofluorescence staining
      with polyclonal antiserum raised against planktonic cells. Further work with
      planktonic cells showed that the immunostained capsule remained associated with
      young (log phase) cells, whereas older (stationary phase) cells lost their
      capsular material to the external milieu. Visualization of frozen, hydrated
      stationary phase cells by cryo-field emission scanning electron microscopy
      (cryoFESEM) revealed highly preserved extracellular material. In contrast,
      conventional scanning electron microscopy (SEM) of stationary phase cells showed
      rope-like material that most probably results from dehydrated and collapsed
      exopolymer. Both capsular and released exopolymers were separated from cells, and
      the released extracellular polysaccharide (EPS) was purified. Deoxycholate
      polyacrylamide gel electrophoresis (PAGE) and silver/alcian blue staining of the
      partially purified material showed that it contained both EPS and
      lipopolysaccharide (LPS). Further purification of the EPS using a differential
      solubilization technique to remove LPS yielded highly purified EPS. Gas
      chromatography-mass spectrometry revealed that the purified EPS contained the
      monosaccharides, glucose, rhamnose, ribose, N-acetylgalactosamine and glucuronic
      acid. The structural and chemical properties of the P. putida EPS described here
      increase our understanding of the mechanisms of toxic metal binding by this well
      known Proteobacterium.

PMID- 11846772
TI  - Strain characterization and 16S-23S probe development for differentiating
      geographically dispersed isolates of the phytopathogen Ralstonia solanacearum.
AB  - The causative agent of potato brown rot and bacterial wilt, Ralstonia
      solanacearum, results in serious world-wide economic losses, particularly in the
      tropics. In the last decade, however, the incidence of bacterial wilt in potatoes
      grown in Northern Europe has increased, presenting an interesting epidemiological
      puzzle. Its occurrence may be as a result of changes in agricultural practice or
      the emergence of a novel bacterial variety, better adapted to cooler conditions.
      To understand the distribution and genetic diversity of this phytopathogen, we
      have analysed a collection of 82 isolates from Europe and tropical regions. Both
      phenotypic [SDS-PAGE (sodium dodecyl sulphate polyacrylamide gel electrophoresis)
      profiling, FAME (fatty acid methyl esters) analysis, growth profiles and EPS
      (exopolysaccharide) production] and genotypic [16S rRNA RFLP (restriction
      fragment length polymorphism), ARDRA (amplified ribosomal DNA restriction
      analysis) and sequence analysis of 16S-23S rRNA ITS and flanking regions] methods
      were compared. Principal component analysis of FAME profiles clustered isolates
      into three groups and ARDRA of a 0.85 kb amplified fragment from the 16S-23S ITS
      region differentiated isolates into four groups. Using sequence analysis,
      specific primers were designed within the variable region 147-170 of the 23S
      rRNA. These primers, RsolT2 and RsolT3, respectively, differentiated isolates
      into two distinct clusters as described previously by Wullings and colleagues
      (Wullings et al., 1998). The European strains (Biovar 2, race 3) analysed in this
      study specifically hybridized with RsolT3, and showed considerable genetic
      homogeneity when compared with strains of other races from 'the rest of the
      world'. These data indicate the possible selection and proliferation of a
      'European'-adapted variant.

PMID- 11846773
TI  - Toxicity and synergism in transgenic Escherichia coli expressing four genes from
      Bacillus thuringiensis subsp. israelensis.
AB  - The genes cyt1Aa and p20, encoding, respectively, cytolytic and accessory
      proteins of Bacillus thuringiensis subsp. israelensis, were introduced into
      previously constructed clones expressing cry4Aa and cry11Aa in Escherichia coli
      (Ben-Dov et al., 1995). Fifteen clones with all possible combinations of the four
      genes were obtained and found to express the genes included. Two new
      combinations, pVE4-ADRC and pVE4-ARC, expressing cyt1Aa, p20 and cry4Aa, with or
      without cry11Aa, respectively, were more toxic than their counterparts without
      cyt1Aa. They displayed the highest toxicity against Aedes aegypti larvae ever
      reached in transgenic bacteria. Five out of the six clones (except pVE4-DC)
      containing cry4Aa or cry11Aa (with or without p20) displayed varying levels of
      synergism with cyt1Aa: they are 1.5-to 34-fold more toxic than the respective
      clones without cyt1Aa against exposed larvae. Their lethal times also decreased
      (they kill larvae quicker), more so at higher cell concentrations. These clones
      are anticipated to dramatically reduce the likelihood of resistant development in
      the target organisms (Wirth et al., 1997).

PMID- 11846775
TI  - Lipid rafts and little caves. Compartmentalized signalling in membrane
      microdomains.
AB  - Lipid rafts are liquid-ordered membrane microdomains with a unique protein and
      lipid composition found on the plasma membrane of most, if not all, mammalian
      cells. A large number of signalling molecules are concentrated within rafts,
      which have been proposed to function as signalling centres capable of
      facilitating efficient and specific signal transduction. This review summarizes
      current knowledge regarding the composition, structure, and dynamic nature of
      lipid rafts, as well as a number of different signalling pathways that are
      compartmentalized within these microdomains. Potential mechanisms through which
      lipid rafts carry out their specialized role in signalling are discussed in light
      of recent experimental evidence.

PMID- 11846776
TI  - Unfolding and refolding studies of frutalin, a tetrameric D-galactose binding
      lectin.
AB  - Protein refolding is currently a fundamental problem in biophysics and molecular
      biology. We have studied the refolding process of frutalin, a tetrameric lectin
      that presents structural homology with jacalin but shows a more marked biological
      activity. The initial state in our refolding puzzle was that proteins were
      unfolded after thermal denaturation or denaturation induced by guanidine
      hydrochloride, and under both conditions, frutalin was refolded. The denaturation
      curves, measured by fluorescence emission, gave values of conformational
      stability of 17.12 kJ x mol(-1) and 12.34 kJ x mol(-1), in the presence and
      absence of d-galactose, respectively. Native, unfolded, refolded frutalin and a
      distinct molecular form denoted misfolded, were separated by size-exclusion
      chromatography (SEC) on Superdex 75. The native and unfolded samples together
      with the fractions separated by SEC were also analyzed for heamagglutination
      activity by CD and fluorescence spectroscopy. The secondary structure content of
      refolded frutalin estimated from the CD spectra was found to be close to that of
      the native molecule. All the results obtained confirmed the successful refolding
      of the protein and suggested a nucleation-condensation mechanism, whereby the
      sugar-binding site acts as a nucleus to initiate the refolding process. The
      refolded monomers, after adopting their native three-dimensional structures,
      spontaneously assemble to form tetramers.

PMID- 11846777
TI  - Human bile salt-stimulated lipase has a high frequency of size variation due to a
      hypervariable region in exon 11.
AB  - The apparent molecular mass of human milk bile salt-stimulated lipase (BSSL)
      varies between mothers. The molecular basis for this is unknown, but indirect
      evidence has suggested the differences to reside in a region of repeats located
      in the C-terminal part of the protein. We here report that a polymorphism within
      exon 11 of the BSSL gene is the explanation for the molecular variants of BSSL
      found in milk. By Southern blot hybridization we analyzed the BSSL gene from
      mothers known to have BSSL of different molecular masses in their milk. A
      polymorphism was found within exon 11, previously shown to consist of 16 near
      identical repeats of 33 bp each. We detected deletions or, in one case, an
      insertion corresponding to the variation in molecular mass of the BSSL protein
      found in milk from the respective woman. Furthermore, we found that 56%, out of
      295 individuals studied, carry deletions or insertions within exon 11 in one or
      both alleles of the BSSL gene. Hence, this is a hypervariable region and the
      current understanding that exon 11 in the human BSSL gene encodes 16 repeats is
      an oversimplification and needs to be revisited. Natural variation in the
      molecular mass of BSSL may have clinical implications.

PMID- 11846778
TI  - Molecular characterization of the amplified aldehyde oxidase from insecticide
      resistant Culex quinquefasciatus.
AB  - Primary structural information including the complete nucleotide sequence of the
      first insect aldehyde oxidase (AO) was obtained from the common house mosquito
      Culex quinquefasciatus (Say) through cloning and sequencing of both genomic DNA
      and cDNA. The deduced amino-acid sequence encodes a 150-kDa protein of 1266 amino
      acid residues, which is consistent with the expected monomeric subunit size of
      AO. The Culex AO sequence contains a molybdopterin cofactor binding domain and
      two iron-sulfur centres. A comparison of the partial sequences of AO from
      insecticide resistant and susceptible strains of C. quinquefasciatus shows two
      distinct alleles of this enzyme, one of which is amplified in the insecticide
      resistant strain on a 30-kb DNA amplicon alongside two resistance-associated
      esterases. The amplified AO gene results in elevated AO activity in all life
      stages, but activity is highest in 3rd instar larvae. The elevated enzyme can be
      seen as a separate band on polyacrylamide gel electrophoresis. The role of AO in
      xenobiotic oxidation in mammals and the partial inhibition of elevated AO
      activity by a range of insecticides in Culex, suggest that this AO may play a
      role in insecticide resistance.

PMID- 11846779
TI  - Conformationally constrained human calcitonin (hCt) analogues reveal a critical
      role of sequence 17-21 for the oligomerization state and bioactivity of hCt.
AB  - Calcitonin (Ct) is a 32-residue peptide hormone that is mainly known for its
      hypocalcemic effect and the inhibition of bone resorption. Our previous studies
      have led to potent, side-chain lactam-bridged human Ct (hCt) analogues
      [Kapurniotu, A. Kayed, R., Taylor, J.W. & Voelter W. (1999) Eur. J. Biochem. 265,
      606-618; Kapurniotu, A. & Taylor, J.W. (1995) J. Med. Chem. 38, 836-847]. We have
      hypothesized that a possibly type I beta turn/beta sheet conformation in the
      region 17-21 may play an important role in hCt bioactivity. To investigate this
      hypothesis, analogues of the potent hCt agonist cyclo17,21-[Asp17,Lys21]hCt (1)
      bearing type I (and II') or II beta turn-promoting substituents at positions 18
      and 19 were designed, synthesized and their solution conformations, human Ct
      receptor binding affinities and in vivo hypocalcemic potencies were assessed. The
      novel analogues include cyclo17,21-[Asp17,D-Phe19, Lys21]hCt (2), cyclo17,21
      [Asp17,Aib18,Lys21]hCt (3), cyclo17,21-[Asp17,D-Lys18,Lys21]hCt (4),
      corresponding partial sequence peptides containing the lactam-bridged region 16
      22, and nonbridged control peptides. Only 1 showed a higher Ct receptor binding
      affinity than hCt, whereas analogues 2-4 had similar receptor affinities to hCt.
      In the in vivo hypocalcemic assay, 3 and 4 were as potent as 1, whereas 2
      completely lost the high potency of 1, suggesting that type I (and II') beta turn
      promoting substituents are fully compatible with in vivo bioactivity. CD
      spectroscopy showed that analogues 1-4 were markedly beta sheet-stabilized
      compared to hCt and indicated the presence of distinct beta turn conformeric
      populations in each of the analogues. Unexpectedly, the D-amino acid- or Aib
      containing cyclic analogues 2-4 but not 1 or hCt self-associated into SDS
      denaturation-stable dimers. Our results demonstrate a crucial role of the
      conformational and topological features of the residues in sequence 17-21 and in
      particular of residues 18 and 19 for human Ct receptor binding and in vivo
      bioactivity and also for the self association state of hCt. These results may
      assist to delineate the structure-function relationships of hCt and to design
      novel hCt agonists for the treatment of osteoporosis and other bone-disorder
      related diseases.

PMID- 11846780
TI  - Implications of the simultaneous occurrence of hepatic glycolysis from glucose
      and gluconeogenesis from glycerol.
AB  - Glycolysis from [6-(3)H]glucose and gluconeogenesis from [U-(14)C]glycerol were
      examined in isolated hepatocytes from fasted rats. A 5 mm bolus of glycerol
      inhibited phosphorylation of 40 mm glucose by 50% and glycolysis by more than
      60%, and caused cellular ATP depletion and glycerol 3-phosphate accumulation.
      Gluconeogenesis from 5 mm glycerol was unaffected by the presence of 40 mm
      glucose. When nonsaturating concentrations of glycerol (< 200 microm) were
      maintained in the medium by infusion of glycerol, cellular ATP concentrations
      remained normal. The rate of uptake of infused glycerol was unaffected by 40 mm
      glucose, but carbohydrate synthesis from glycerol was inhibited 25%, a
      corresponding amount of glycerol being diverted to glycolytic products, whereas
      10 mm glucose had no inhibitory effect on conversion of infused glycerol into
      carbohydrate. Glycerol infusion depressed glycolysis from 10 mm and 40 mm glucose
      by 15 and 25%, respectively; however, the overall rates of glycolysis were
      unchanged because of a concomitant increase in glycolysis from the infused
      glycerol. These studies show that exposure of hepatocytes to glucose and low
      quasi-steady-state concentrations of glycerol result in the simultaneous
      occurrence, at substantial rates, of glycolysis from glucose and gluconeogenesis
      from the added glycerol. We interpret our results as demonstrating that, in
      hepatocytes from normal rats, segments of the pathways of glycolysis from glucose
      and gluconeogenesis from glycerol are compartmentalized and that this segregation
      prevents substantial cross-over of phosphorylated intermediates from one pathway
      to the other. The competition between glucose and glycerol implies that
      glycolysis and phosphorylation of glycerol take place in the same cells, and that
      the occurrence of simultaneous glycolysis and gluconeogenesis may indicate
      channelling within the cytoplasm of individual hepatocytes.

PMID- 11846781
TI  - Purification and properties of an alkaline proteinase of Fusarium culmorum.
AB  - The disease Fusarium head blight (scab) causes severe problems for farmers and
      for the industries that use cereals. It is likely that the fungi that cause scab
      (Fusarium spp.) use various enzymes when they invade grains. We are studying
      enzymes that the fungi may use to hydrolyze grain proteins. To do this, Fusarium
      culmorum was grown in a gluten-containing medium from which an alkaline serine
      proteinase with a molecular mass of 28.7 kDa was purified by size-exclusion and
      cation exchange chromatographies. The enzyme was maximally active at pH 8.3-9.6
      and 50 degrees C, but was unstable under these conditions. It hydrolyzed the
      synthetic substrates N-succinyl-Ala-Ala-Pro-Phe p-nitroanilide and, to a lesser
      extent, N-succinyl-Ala-Ala-Pro-Leu p-nitroanilide. It was inhibited by
      phenylmethanesulfonyl fluoride and chymostatin, but not by soybean trypsin or
      Bowman-Birk inhibitors. Parts of the amino-acid sequence were up to 82%
      homologous with those of several fungal subtilisins. One of the active site amino
      acids was detected and it occupied the same relative position as in the other
      subtilisins. Therefore, on the basis of these characteristics, the proteinase is
      subtilisin-like. Purification of the enzyme was complicated by the fact that,
      when purified, it apparently underwent autolysis. The presence of extraneous
      protein stabilized the activity.

PMID- 11846782
TI  - Structural analysis of the lipopolysaccharide from nontypeable Haemophilus
      influenzae strain 1003.
AB  - Structural analysis of the lipopolysaccharide (LPS) of nontypeable Haemophilus
      influenzae strain 1003 has been achieved by the application of high-field NMR
      techniques, ESI-MS, capillary electrophoresis coupled to ESI-MS, composition and
      linkage analyses on O-deacylated LPS and core oligosaccharide material. It was
      found that the LPS contains the common structural element of H. influenzae, l
      alpha-D-Hepp-(1-->2)-[PEtn-->6]-l-alpha-D-Hepp-(1-->3)-[beta-D-Glcp-(1-->4)]-l
      alpha-D-Hepp-(1-->5)-[PP Etn-->4]-alpha-Kdop-(2-->6)-Lipid A, in which the beta-D
      Glcp residue is substituted by phosphocholine at O-6 and an acetyl group at O-4.
      A second acetyl group is located at O-3 of the distal heptose residue (HepIII).
      HepIII is chain elongated at O-2 by either a beta-D-Glcp residue (major), lactose
      or sialyllactose (minor, i.e. alpha-Neu5Ac-(2-->3)-beta-D-Galp-(1-->4)-beta-D
      Glcp), where a third minor acetylation site was identified at the glucose
      residue. Disialylated species were also detected. In addition, a minor
      substitution of ester-linked glycine at HepIII and Kdo was observed.

PMID- 11846783
TI  - Characterization of a novel silkworm (Bombyx mori) phenol UDP
      glucosyltransferase.
AB  - Sugar conjugation is a major pathway for the inactivation and excretion of both
      endogenous and exogenous compounds. We report here the molecular cloning and
      functional characterization of a phenol UDP-glucosyltransferase (UGT) from the
      silkworm, Bombyx mori, which was named BmUGT1. The complete cDNA clone is 1.6 kb,
      and the gene is expressed in several tissues of fifth-instar larvae, including
      fat body, midgut, integument, testis, silk gland and haemocytes. The predicted
      protein comprises 520 amino acids and has approximately 30% overall amino-acid
      identity with other members of the UGT family. The most conserved region of the
      protein is the C-terminal half, which has been implicated in binding the UDP
      sugar. BmUGT1 was expressed in insect cells using the baculovirus expression
      system, and a range of compounds belonging to diverse chemical groups were
      assessed as potential substrates for the enzyme. The expressed enzyme had a wide
      substrate specificity, showing activity with flavonoids, coumarins, terpenoids
      and simple phenols. These results support a role for the enzyme in detoxication
      processes, such as minimizing the harmful effects of ingested plant
      allelochemicals. This work represents the first instance where an insect ugt gene
      has been associated with a specific enzyme activity.

PMID- 11846784
TI  - Leucine aminopeptidase during meiotic development.
AB  - We found a leucine aminopeptidase (LAP; EC 3.4.11.1) to be abundant in meiotic
      prophase tissue of a basidiomycete, Coprinus cinereus. After direct purification
      of the aminopeptidase component from meiocytes, we cloned the gene by degenerate
      PCR using partial amino-acid sequences of the purified enzyme and 5' and 3' RACE.
      It was homologous to the eukaryotic leucine aminopeptidase gene. The recombinant
      protein possesses the characteristic activities of a Coprinus leucine
      aminopeptidase (CoLAP) with a molecular mass of 52.4 kDa, and forms a
      homohexamer. Northern blot and spatial distribution analysis by
      immunohistochemical staining indicated CoLAP to be abundant in meiotic prophase
      cells and the supporting cells around meiocytes, but scarce in mycelium cells.
      Interestingly, from zygotene to pachytene, CoLAP was mostly present in supporting
      cells around meiocytes, but from diplotene onwards, it was plentiful in meiocytes
      themselves, suggesting that its expression is required to control some of the
      biochemical events at meiotic prophase. Moreover, the strong expression of CoLAP
      mRNA immediately after treatment with methyl methanesulfonate in mycelium implies
      that CoLAP has a role in somatic DNA repair.

PMID- 11846785
TI  - Intermonomer flexibility of Ca- and Mg-actin filaments at different pH values.
AB  - The fluorescence resonance energy transfer parameter, f, is defined as the
      efficiency of the energy transfer normalized by the quantum yield of the donor in
      the presence of acceptor. It is possible to characterize the flexibility of the
      protein matrix between the appropriate fluorescent probes by monitoring the
      temperature dependence of f. The intermonomer flexibility of the Ca-actin and Mg
      actin filaments was characterized by using this method at pH values of 6.5 and
      7.4. The protomers were labeled on Cys374 with donor [N
      (((iodoacetyl)amino)ethyl)-5-naphthylamine-1-sulfonate; IAEDANS] or acceptor [5
      (iodoacetamido)fluorescein; IAF] molecules. The temperature profile of f
      suggested that the intermonomer flexibility of actin filaments was larger at pH
      7.4 than pH 6.5 in the case of Mg-F-actin while this difference was absent in the
      case of Ca-F-actin. More rigid intermonomer connection was identified at both pH
      values between the protomers of Mg-F-actin compared to the Ca-F-actin. The
      results were further supported by time dependent fluorescence measurements made
      on IAEDANS and IAF labeled Mg- and Ca-actin filaments at pH 6.5 and 7.4. Our
      spectroscopic results may suggest that the altered function of muscle following
      the change of pH within the muscle cells under physiological or pathological
      conditions might be affected by the modified dynamic properties of the magnesium
      saturated actin filaments. The change of the intracellular pH does not have an
      effect on the intermonomer flexibility of the Ca-actin filaments.

PMID- 11846787
TI  - The processivity and fidelity of DNA synthesis exhibited by the reverse
      transcriptase of bovine leukemia virus.
AB  - We have recently expressed in bacteria the enzymatically active reverse
      transcriptase (RT) of bovine leukemia virus (BLV) [Perach, M. & Hizi, A. (1999)
      Virology 259, 176-189]. In the present study, we have studied in vitro two
      features of the DNA polymerase activity of BLV RT, the processivity of DNA
      synthesis and the fidelity of DNA synthesis. These properties were compared with
      those of the well-studied RTs of human immunodeficiency virus type 1 (HIV-1) and
      murine leukaemia virus (MLV). Both the elongation of the DNA template and the
      processivity of DNA synthesis exhibited by BLV RT are impaired relative to the
      other two RTs studied. Two parameters of fidelity were studied, the capacity to
      incorporate incorrect nucleotides at the 3' end of the nascent DNA strand and the
      ability to extend these 3' end mispairs. BLV RT shows a fidelity of misinsertion
      higher than that of HIV-1 RT and lower than that of MLV RT. The pattern of
      mispair elongation by BLV RT suggests that the in vitro error proneness of BLV RT
      is closer to that of HIV-1 RT. These fidelity properties are discussed in the
      context of the various retroviral RTs studied so far.

PMID- 11846786
TI  - Mitogen-activated protein kinase kinase negatively modulates ciliary neurotrophic
      factor-activated choline acetyltransferase gene expression.
AB  - The expression of the choline acetyltransferase (ChAT) enzyme that synthesizes
      the neurotransmitter acetylcholine (ACh) is upregulated by ciliary neurotrophic
      factor (CNTF). We studied the involvement of the mitogen-activated protein kinase
      (MAPK) pathway in regulating ChAT expression in a murine septal cell line.
      Surprisingly, we found that PD98059 and U0126, two structurally distinct
      inhibitors of MAPK kinase (MEK1), increased both basal and CNTF-induced ACh
      production. Transient transfections with ChAT promoter-luciferase reporter
      construct demonstrated synergy between PD98059 and CNTF at the transcriptional
      level. Moreover, in cotransfection studies, overexpression of constitutively
      activated MEK1 completely abrogated the CNTF-mediated induction of the reporter.
      Blocking MEK1 did not significantly alter CNTF-induced Tyr705 phosphorylation of
      the principal mediator of the CNTF pathway, the transcription factor Stat3.
      However, PD98059 inhibited Ser727 phosphorylation of Stat3, demonstrating that
      the latter is MEK1-dependent. Taken together, these results indicate that
      activation of the MEK1/MAPK pathway inhibits the CNTF-mediated stimulation of
      ChAT expression, possibly as a part of a feedback mechanism.

PMID- 11846788
TI  - Evolution of the enzymes of the citric acid cycle and the glyoxylate cycle of
      higher plants. A case study of endosymbiotic gene transfer.
AB  - The citric acid or tricarboxylic acid cycle is a central element of higher-plant
      carbon metabolism which provides, among other things, electrons for oxidative
      phosphorylation in the inner mitochondrial membrane, intermediates for amino-acid
      biosynthesis, and oxaloacetate for gluconeogenesis from succinate derived from
      fatty acids via the glyoxylate cycle in glyoxysomes. The tricarboxylic acid cycle
      is a typical mitochondrial pathway and is widespread among alpha-proteobacteria,
      the group of eubacteria as defined under rRNA systematics from which mitochondria
      arose. Most of the enzymes of the tricarboxylic acid cycle are encoded in the
      nucleus in higher eukaryotes, and several have been previously shown to branch
      with their homologues from alpha-proteobacteria, indicating that the eukaryotic
      nuclear genes were acquired from the mitochondrial genome during the course of
      evolution. Here, we investigate the individual evolutionary histories of all of
      the enzymes of the tricarboxylic acid cycle and the glyoxylate cycle using
      protein maximum likelihood phylogenies, focusing on the evolutionary origin of
      the nuclear-encoded proteins in higher plants. The results indicate that about
      half of the proteins involved in this eukaryotic pathway are most similar to
      their alpha-proteobacterial homologues, whereas the remainder are most similar to
      eubacterial, but not specifically alpha-proteobacterial, homologues. A
      consideration of (a) the process of lateral gene transfer among free-living
      prokaryotes and (b) the mechanistics of endosymbiotic (symbiont-to-host) gene
      transfer reveals that it is unrealistic to expect all nuclear genes that were
      acquired from the alpha-proteobacterial ancestor of mitochondria to branch
      specifically with their homologues encoded in the genomes of contemporary alpha
      proteobacteria. Rather, even if molecular phylogenetics were to work perfectly
      (which it does not), then some nuclear-encoded proteins that were acquired from
      the alpha-proteobacterial ancestor of mitochondria should, in phylogenetic trees,
      branch with homologues that are no longer found in most alpha-proteobacterial
      genomes, and some should reside on long branches that reveal affinity to
      eubacterial rather than archaebacterial homologues, but no particular affinity
      for any specific eubacterial donor.

PMID- 11846790
TI  - Expression and characterization of active site mutants of hevamine, a chitinase
      from the rubber tree Hevea brasiliensis.
AB  - Hevamine is a chitinase from the rubber tree Hevea brasiliensis. Its active site
      contains Asp125, Glu127, and Tyr183, which interact with the -1 sugar residue of
      the substrate. To investigate their role in catalysis, we have successfully
      expressed wild-type enzyme and mutants of these residues as inclusion bodies in
      Escherichia coli. After refolding and purification they were characterized by
      both structural and enzyme kinetic studies. Mutation of Tyr183 to phenylalanine
      produced an enzyme with a lower k(cat) and a slightly higher K(m) than the wild
      type enzyme. Mutating Asp125 and Glu127 to alanine gave mutants with
      approximately 2% residual activity. In contrast, the Asp125Asn mutant retained
      substantial activity, with an approximately twofold lower k(cat) and an
      approximately twofold higher K(m) than the wild-type enzyme. More interestingly,
      it showed activity to higher pH values than the other variants. The X-ray
      structure of the Asp125Ala/Glu127Ala double mutant soaked with chitotetraose
      shows that, compared with wild-type hevamine, the carbonyl oxygen atom of the N
      acetyl group of the -1 sugar residue has rotated away from the C1 atom of that
      residue. The combined structural and kinetic data show that Asp125 and Tyr183
      contribute to catalysis by positioning the carbonyl oxygen of the N-acetyl group
      near to the C1 atom. This allows the stabilization of a positively charged
      transient intermediate, in agreement with a previous proposal that the enzyme
      makes use of substrate-assisted catalysis.

PMID- 11846789
TI  - Agmatine oxidation by copper amine oxidase.
AB  - The product of agmatine oxidation catalyzed by Pisum sativum L. copper amine
      oxidase has been identified by means of one- and two-dimensional (1)H-NMR
      spectroscopy to be N-amidino-2-hydroxypyrrolidine. This compound inhibits
      competitively rat nitric oxide synthase type I and type II (NOS-I and NOS-II,
      respectively) and bovine trypsin (trypsin) activity, values of Ki being (1.1 +/-
      0.1) x 10(-5) m (at pH 7.5 and 37.0 degrees C), (2.1 +/- 0.1) x 10(-5) m (at pH
      7.5 and 37.0 degrees C), and (8.9 +/- 0.4) x 10(-5) m (at pH 6.8 and 21.0 degrees
      C), respectively. Remarkably, the affinity of N-amidino-2-hydroxypyrrolidine for
      NOS-I, NOS-II and trypsin is significantly higher than that observed for agmatine
      and clonidine binding. Furthermore, N-amidino-2-hydroxypyrrolidine and agmatine
      are more efficient than clonidine in displacing [(3)H]clonidine (= 1.0 x 10(-8)
      m) from specific binding sites in heart rat membranes, values of IC50 being (1.3
      +/- 0.4) x 10(-9) m and (2.2 +/- 0.4) x 10(-8) m, respectively (at pH 7.4 and
      37.0 degrees C).

PMID- 11846791
TI  - Interallelic complementation provides genetic evidence for the multimeric
      organization of the Phycomyces blakesleeanus phytoene dehydrogenase.
AB  - The Phycomyces blakesleeanus wild-type is yellow, because it accumulates beta
      carotene as the main carotenoid. A new carotenoid mutant of this fungus (A486)
      was isolated, after treatment with ethyl methane sulfonate (EMS), showing a
      whitish coloration. It accumulates large amounts of phytoene, small quantities of
      phytofluene, zeta-carotene and neurosporene, in decreasing amounts, and traces of
      beta-carotene. This phenotype indicates that it carries a leaky mutation
      affecting the enzyme phytoene dehydrogenase (EC 1.3.-.-), which is specified by
      the gene carB. Biochemical analysis of heterokaryons showed that mutant A486
      complements two previously characterized carB mutants, C5 (carB10) and S442
      (carB401). Sequence analysis of the carB gene genomic copy from these three
      strains revealed that they are all altered in the gene carB, giving information
      about the nature of the mutation in each carB mutant allele. The interallelic
      complementation provides evidence for the multimeric organization of the P.
      blakesleeanus phytoene dehydrogenase.

PMID- 11846792
TI  - Identification of syntaxin-1A sites of phosphorylation by casein kinase I and
      casein kinase II.
AB  - Casein kinases I (CKI) are serine/threonine protein kinases widely expressed in a
      range of eukaryotes including yeast, mammals and plants. They have been shown to
      play a role in diverse physiological events including membrane trafficking. CKI
      alpha is associated with synaptic vesicles and phosphorylates some synaptic
      vesicle associated proteins including SV2. In this report, we show that syntaxin
      1A is phosphorylated in vitro by CKI on Thr21. Casein kinase II (CKII) has been
      shown previously to phosphorylate syntaxin-1A in vitro and we have identified
      Ser14 as the CKII phosphorylation site, which is known to be phosphorylated in
      vivo. As syntaxin-1A plays a key role in the regulation of neurotransmitter
      release by forming part of the SNARE (soluble N-ethylmaleimide-sensitive factor
      attachment protein receptor) complex, we propose that CKI may play a role in
      synaptic vesicle exocytosis.

PMID- 11846793
TI  - Targeting of malate synthase 1 to the peroxisomes of Saccharomyces cerevisiae
      cells depends on growth on oleic acid medium.
AB  - The eukaryotic glyoxylate cycle has been previously hypothesized to occur in the
      peroxisomal compartment, which in the yeast Saccharomyces cerevisiae additionally
      represents the sole site for fatty acid beta-oxidation. The subcellular location
      of the key glyoxylate-cycle enzyme malate synthase 1 (Mls1p), an SKL-terminated
      protein, was examined in yeast cells grown on different carbon sources.
      Immunoelectron microscopy in combination with cell fractionation showed that
      Mls1p was abundant in the peroxisomes of cells grown on oleic acid, whereas in
      ethanol-grown cells Mls1p was primarily cytosolic. This was reinforced using a
      green fluorescent protein (GFP)-Mls1p reporter, which entered peroxisomes solely
      in cells grown under oleic acid-medium conditions. Although growth of cells
      devoid of Mls1p on ethanol or acetate could be fully restored using a cytosolic
      Mls1p devoid of SKL, this construct could only partially alleviate the
      requirement for native Mls1p in cells grown on oleic acid. The combined results
      indicated that Mls1p remained in the cytosol of cells grown on ethanol, and that
      targeting of Mls1p to the peroxisomes was advantageous to cells grown on oleic
      acid as a sole carbon source.

PMID- 11846794
TI  - Antimicrobial dendrimeric peptides.
AB  - Dendrimeric peptides selective for microbial surfaces have been developed to
      achieve broad antimicrobial activity and low hemolytic activity to human
      erythrocytes. The dendrimeric core is an asymmetric lysine branching tethered
      with two to eight copies of a tetrapeptide (R4) or an octapeptide (R8). The R4
      tetrapeptide (RLYR) contains a putative microbial surface recognition BHHB motif
      (B = basic, H = hydrophobic amino acid) found in protegrins and tachyplesins
      whereas the octapeptide R8 (RLYRKVYG) consists of an R4 and a degenerated R4
      repeat. Antimicrobial assays against 10 organisms in high- and low-salt
      conditions showed that the R4 and R8 monomers as well as their divalent
      dendrimers contain no to low activity. In contrast, the tetra- and octavalent R4
      and R8 dendrimers are broadly active under either conditions, exhibiting
      relatively similar potency with minimal inhibition concentrations < 1 microm
      against both bacteria and fungi. Based on their size and charge similarities, the
      potency and activity spectrum of the tetravalent R4 dendrimer are comparable to
      protegrins and tachyplesins, a family of potent antimicrobials containing 17-19
      residues. Compared with a series of linearly repeating R4 peptides, the R4
      dendrimers show comparable antimicrobial potency, but are more aqueous soluble,
      more stable to proteolysis, less toxic to human cells and more easily synthesized
      chemically. These results suggest repeating peptides that cluster the charge and
      hydrophobic residues may represent a primitive form of microbial pattern
      recognition. Incorporating such knowledge in a dendrimeric design therefore
      presents an attractive approach for developing novel peptide antibiotics.

PMID- 11846795
TI  - Functional analysis of a small heat shock/alpha-crystallin protein from Artemia
      franciscana. Oligomerization and thermotolerance.
AB  - Oviparously developing embryos of the brine shrimp, Artemia franciscana,
      synthesize abundant quantities of a small heat shock/alpha-crystallin protein,
      termed p26. Wild-type p26 functions as a molecular chaperone in vitro and is
      thought to help encysted Artemia embryos survive severe physiological stress
      encountered during diapause and anoxia. Full-length and truncated p26 cDNA
      derivatives were generated by PCR amplification of p26-3-6-3, then cloned in
      either pET21(+) or pRSETC and expressed in Escherichia coli BL21(DE3). All
      constructs gave a polypeptide detectable on Western blots with either p26
      specific antibody, or with antibody to the His(6) epitope tag encoded by pRSETC.
      Full-length p26 in cell-free extracts of E. coli was about equal in mass to that
      found in Artemia embryos, but p26 lacking N- and C-terminal residues remained
      either as monomers or small multimers. All p26 constructs conferred
      thermotolerance on transformed E. coli, although not all formed oligomers, and
      cells expressing N-terminal truncated derivatives of p26 were more heat resistant
      than bacteria expressing p26 with C-terminal deletions. The C-terminal extension
      of p26 is seemingly more important for thermotolerance than is the N-terminus,
      and p26 protects E. coli against heat shock when oligomer size and protein
      concentration are low. The findings have important implications for understanding
      the functional mechanisms of small heat shock/alpha-crystallin proteins.

PMID- 11846796
TI  - The binding of lamin B receptor to chromatin is regulated by phosphorylation in
      the RS region.
AB  - Binding of lamin B receptor (LBR) to chromatin was studied by means of an in
      vitro assay system involving recombinant fragments of human LBR and Xenopus sperm
      chromatin. Glutathione-S-transferase (GST)-fused proteins including LBR fragments
      containing the N-terminal region (residues 1-53) and arginine-serine repeat
      containing region (residues 54-89) bound to chromatin. The binding of GST-fusion
      proteins incorporating the N-terminal and arginine-serine repeat-containing
      regions to chromatin was suppressed by mild trypsinization of the chromatin and
      by pretreatment with a DNA solution. A new cell-free system for analyzing the
      cell cycle-dependent binding of a protein to chromatin was developed from
      recombinant proteins, a Xenopus egg cytosol fraction and sperm chromatin. The
      system was applied to analyse the binding of LBR to chromatin. It was shown that
      the binding of LBR fragments to chromatin was stimulated by phosphorylation in
      the arginine-serine repeat-containing region by a protein kinase(s) in a
      synthetic phase egg cytosol. However, the binding of LBR fragments was suppressed
      by phosphorylation at different residues in the same region by a kinase(s) in a
      mitotic phase cytosol. These results suggested that the cell cycle-dependent
      binding of LBR to chromatin is regulated by phosphorylation in the arginine
      serine repeat-containing region by multiple kinases.

PMID- 11846798
TI  - Characteristics of binding of insulin-like growth factor (IGF)-I and IGF-II
      analogues to the type 1 IGF receptor determined by BIAcore analysis.
AB  - Insulin-like growth factor (IGF) binding to the type 1 IGF receptor (IGF1R)
      elicits mitogenic effects, promotion of differentiation and protection from
      apoptosis. This study has systematically measured IGF1R binding affinities of IGF
      I, IGF-II and 14 IGF analogues to a recombinant high-affinity form of the IGF1R
      using BIAcore technology. The analogues assessed could be divided into two
      groups: (a) those designed to investigate binding of IGF-binding protein, which
      exhibited IGF1R-binding affinities similar to those of IGF-I or IGF-II; (b) those
      generated to probe IGF1R interactions with greatly reduced IGF1R-binding
      affinities. The relative binding affinities of IGF-I analogues and IGF-I for the
      IGF1R determined by BIAcore analysis agreed closely with existing data from
      receptor-binding assays using cells or tissue membranes, demonstrating that
      BIAcore technology is a powerful tool for measuring affinities of IGFs for IGF1R.
      In parallel studies, IGF1R-binding affinities were related to ability to protect
      against serum withdrawal-induced apoptosis in three different assays including
      Hoechst 33258 staining, cell survival, and DNA fragmentation assays using the rat
      pheochromocytoma cell line, PC12. In this model system, IGF-I and IGF-II at low
      nanomolar concentrations are able to prevent apoptosis completely. We conclude
      that ability to protect against apoptosis is directly related to ability to bind
      the IGF1R.

PMID- 11846797
TI  - Interaction of the anterior fat body protein with the hexamerin receptor in the
      blowfly Calliphora vicina.
AB  - In late larvae of the blowfly, Calliphora vicina, arylphorin and LSP-2 proteins,
      which belong to the class of hexamerins, are selectively taken up by the fat body
      from the haemolymph. Hexamerin endocytosis is mediated by a specific membrane
      bound receptor, the arylphorin-binding protein (ABP). Using the two-hybrid
      technique, we found that the anterior fat body protein (AFP) interacts with the
      hexamerin receptor. AFP, a homologue of the mammalian calcium-binding liver
      protein regucalcin (senescence marker protein-30), exhibits a strong binding
      affinity for a naturally occurring C-terminal cleavage fragment of the hexamerin
      receptor precursor (the P30 peptide) and other receptor cleavage products that
      contain P30. Expression of AFP mRNA and protein is restricted to the anterior
      part of the fat body tissue and to haemocytes in last-instar larvae. AFP mRNA
      occurs in all postembryonic developmental stages. Our results suggest that AFP
      plays a role in the regulation of hexamerin uptake by fat body cells along the
      anterior-posterior axis.

PMID- 11846799
TI  - Kinetic study of sn-glycerol-1-phosphate dehydrogenase from the aerobic
      hyperthermophilic archaeon, Aeropyrum pernix K1.
AB  - A gene having high sequence homology (45-49%) with the glycerol-1-phosphate
      dehydrogenase gene from Methanobacterium thermoautotrophicum was cloned from the
      aerobic hyperthermophilic archaeon Aeropyrum pernix K1 (JCM 9820). This gene
      expressed in Escherichia coli with the pET vector system consists of 1113
      nucleotides with an ATG initiation codon and a TAG termination codon. The
      molecular mass of the purified enzyme was estimated to be 38 kDa by SDS/PAGE and
      72.4 kDa by gel column chromatography, indicating presence as a dimer. The
      optimum reaction temperature of this enzyme was observed to be 94-96 degrees C at
      near neutral pH. This enzyme was subjected to two-substrate kinetic analysis. The
      enzyme showed substrate specificity for NAD(P)H-dependent dihydroxyacetone
      phosphate reduction and NAD(+)-dependent glycerol-1-phosphate (Gro1P) oxidation.
      NADP(+)-dependent Gro1P oxidation was not observed with this enzyme. For the
      production of Gro1P in A. pernix cells, NADPH is the preferred coenzyme rather
      than NADH. Gro1P acted as a noncompetitive inhibitor against dihydroxyacetone
      phosphate and NAD(P)H. However, NAD(P)(+) acted as a competitive inhibitor
      against NAD(P)H and as a noncompetitive inhibitor against dihydroxyacetone
      phosphate. This kinetic data indicates that the catalytic reaction by glycerol- 1
      phosphate dehydrogenase from A. pernix follows a ordered bi-bi mechanism.

PMID- 11846800
TI  - Tyrosine sulfation and N-glycosylation of human heparin cofactor II from plasma
      and recombinant Chinese hamster ovary cells and their effects on heparin binding.
AB  - The structure of post-translational modifications of human heparin cofactor II
      isolated from human serum and from recombinant Chinese hamster ovary cells and
      their effects on heparin binding have been characterized. Oligosaccharide chains
      were found attached to all three potential N-glycosylation sites in both protein
      preparations. The carbohydrate structures of heparin cofactor II circulating in
      blood are complex-type diantennary and triantennary chains in a ratio of 6 : 1
      with the galactose being > 90% sialylated with alpha 2-->6 linked N
      acetylneuraminic acid. About 50% of the triantennary structures contain one
      sLe(x) motif. Proximal alpha 1-->6 fucosylation of oligosacharides from Chinese
      hamster ovary cell-derived HCII was detected in > 90% of the diantennary and
      triantennary glycans, the latter being slightly less sialylated with exclusively
      alpha 2-->3-linked N-acetylneuraminic acid units. Applying the ESI-MS/ MS-MS
      technique, we demonstrate that the tryptic peptides comprising tyrosine residues
      in positions 60 and 73 were almost completely sulfated irrespective of the
      protein's origin. Treatment of transfected Chinese hamster ovary cells with
      chlorate or tunicamycin resulted in the production of heparin cofactor II
      molecules that eluted with higher ionic strength from heparin-Sepharose,
      indicating that tyrosine sulfation and N-linked glycans may affect the
      inhibitor's interaction with glycosaminoglycans.

PMID- 11846801
TI  - Ductus ejaculatorius peptide 99B (DUP99B), a novel Drosophila melanogaster sex
      peptide pheromone.
AB  - We have characterized a glycosylated, 31 amino-acid peptide of 4932 Da isolated
      from Drosophila melanogaster males. The mature peptide contains a sugar moiety of
      1184 Da at a NDT consensus glycosylation site and a disulfide bond. It is
      synthesized in the male ejaculatory duct via a 54 amino-acid precursor containing
      an N-terminal signal peptide and Arg-Lys at the C-terminus which is cleaved off
      during maturation. The gene contains an intron of 53 bp and is localized in the
      cytological region 99B of the D. melanogaster genome. The peptide is therefore
      named DUP99B (for ductus ejaculatorius peptide, cytological localization 99B).
      The C-terminal parts of mature DUP99B and D. melanogaster sex-peptide (ACP70A)
      are highly homologous. Injected into virgin females, DUP99B elicits the same
      postmating responses as sex-peptide (increased oviposition, reduced receptivity).
      These effects are also induced by de-glycosylated native peptide or synthetic
      DUP99B lacking the sugar moiety. Presence of the glycosyl group, however,
      decreases the amount needed to elicit the postmating responses. Homologies in the
      coding regions of the two exons of DUP99B and sex-peptide, respectively, suggest
      that the two genes have evolved by gene duplication. Thus, we consider these two
      genes to be members of the new sex-peptide gene family.

PMID- 11846802
TI  - The nuclear genome is involved in heteroplasmy control in a mitochondrial mutant
      strain of Drosophila subobscura.
AB  - Most (78%) mitochondrial genomes in the studied mutant strain of Drosophila
      subobscura have undergone a large-scale deletion (5 kb) in the coding region.
      This mutation is stable, and is transmitted intact to the offspring. This animal
      model of major rearrangements of mitochondrial genomes can be used to analyse the
      involvement of the nuclear genome in the production and maintenance of these
      rearrangements. Successive backcrosses between mutant strain females and wild
      type males yield a biphasic change in heteroplasmy level: (a) a 5% decrease in
      mutated genomes per generation (from 78 to 55%), until the nuclear genome is
      virtually replaced by the wild-type genome (seven to eight crosses); and (b) a
      continuous decrease of 0.5% per generation when the nuclear context is completely
      wild-type. In parallel with these changes, NADH dehydrogenase activity, which is
      halved in the mutant strain (five subunits of this complex are affected by the
      mutation), gradually increases and stabilizes near the wild-type activity. A
      return to a nuclear context is accompanied by the opposite phenomena: progressive
      increase in heteroplasmy level and stabilization at the value seen in the wild
      type strain and a decrease in the activity of complex I. These results indicate
      that the nuclear genome plays an important role in the control of heteroplasmy
      level and probably in the production of rearranged genomes.

PMID- 11846803
TI  - In vivo activation of plasma membrane H(+)-ATPase hydrolytic activity by complex
      lipid-bound unsaturated fatty acids in Ustilago maydis.
AB  - As an adaptation process to the growth retardation provoked by the presence of
      nonlethal concentrations of ergosterol biosynthesis inhibitors, Ustilago maydis
      alters the ratio of linoleic to oleic acid bound to plasma membrane complex
      lipids [Hernandez, A., Cooke, D.T., Lewis, M. & Clarkson, D.T. (1997)
      Microbiology 143, 3165-3174]. This alteration increases plasma membrane H(+)
      ATPase hydrolytic activity. Activation of H(+)-ATPase by the linoleic/oleic acid
      proportion is noncompetitive, nonessential and only involves changes in the
      maximum velocity of the pump. Optimum pH, affinity to MgATP and constants for the
      inhibition by vanadate and erythrosin B remain unchanged. This all indicates that
      activation of plasma membrane H(+)-ATPase by unsaturated fatty acids differs
      clearly from glucose-induced activation observed in yeast. Also, it is a
      physiologically relevant event similar to other, as yet uncharacterized, changes
      in plasma membrane H(+)-ATPase hydrolytic activity observed in plants and fungi,
      as part of an adaptation process to different stress conditions.

PMID- 11846804
TI  - Transient activation of the c-Jun N-terminal kinase (JNK) activity by ligation of
      the tetraspan CD53 antigen in different cell types.
AB  - The CD53 antigen is a member of the tetraspanin membrane protein family that is
      expressed in the lymphoid-myeloid lineage. We have studied the implication of
      CD53 antigen in signal transduction by determining the effect of its ligation on
      the c-Jun N-terminal kinase (JNK) in different cell types. Ligation of the rat or
      human CD53 antigen induces a three- to fourfold transient activation of JNK
      activity that peaks at 3-5 min. The effect was detected by assaying the
      endogenous or exogenous (transfected) JNK activity. The JNK response was detected
      in IR938F cells, a rat B-cell lymphoma, and in Jurkat cells derived from a human
      T-cell lymphoma. This JNK activation was not mediated by the vav oncogene, and
      CD53 does not cooperate with CD3 for vav activation. A similar JNK activation was
      also detected in a human renal carcinoma cell line that was transiently
      transfected with the human CD53 cDNA to mimic the CD53 ectopic expression in
      carcinomas. In stable CD53-transfected cells it stimulated Jun-dependent
      transcriptional activity. We conclude that parts of the cell responses modulated
      by the CD53 are mediated by JNK activation, and this activation is independent of
      the different protein interactions that the CD53 protein has on specific cell
      types.

PMID- 11846805
TI  - Differential regulation of the Fe-hydrogenase during anaerobic adaptation in the
      green alga Chlamydomonas reinhardtii.
AB  - Chlamydomonas reinhardtii, a unicellular green alga, contains a hydrogenase
      enzyme, which is induced by anaerobic adaptation of the cells. Using the
      suppression subtractive hybridization (SSH) approach, the differential expression
      of genes under anaerobiosis was analyzed. A PCR fragment with similarity to the
      genes of bacterial Fe-hydrogenases was isolated and used to screen an anaerobic
      cDNA expression library of C. reinhardtii. The cDNA sequence of hydA contains a
      1494-bp ORF encoding a protein with an apparent molecular mass of 53.1 kDa. The
      transcription of the hydrogenase gene is very rapidly induced during anaerobic
      adaptation of the cells. The deduced amino-acid sequence corresponds to two
      polypeptide sequences determined by sequence analysis of the isolated native
      protein. The Fe-hydrogenase contains a short transit peptide of 56 amino acids,
      which routes the hydrogenase to the chloroplast stroma. The isolated protein
      belongs to a new class of Fe-hydrogenases. All four cysteine residues and 12
      other amino acids, which are strictly conserved in the active site (H-cluster) of
      Fe-hydrogenases, have been identified. The N-terminus of the C. reinhardtii
      protein is markedly truncated compared to other non-algal Fe-hydrogenases.
      Further conserved cysteines that coordinate additional Fe-S-cluster in other Fe
      hydrogenases are missing. Ferredoxin PetF, the natural electron donor, links the
      hydrogenase from C. reinhardtii to the photosynthetic electron transport chain.
      The hydrogenase enables the survival of the green algae under anaerobic
      conditions by transferring the electrons from reducing equivalents to the enzyme.

PMID- 11846806
TI  - Rapid caspase-dependent cell death in cultured human breast cancer cells induced
      by the polyamine analogue N(1),N(11)-diethylnorspermine.
AB  - The spermine analogue N(1),N(11)-diethylnorspermine (DENSPM) efficiently depletes
      the cellular pools of putrescine, spermidine and spermine by down-regulating the
      activity of the polyamine biosynthetic enzymes and up-regulating the activity of
      the catabolic enzyme spermidine/ spermine N(1)-acetyltransferase (SSAT). In the
      breast cancer cell line L56Br-C1, treatment with 10 microm DENSPM induced SSAT
      activity 60 and 240-fold at 24 and 48 h after seeding, respectively, which
      resulted in polyamine depletion. Cell proliferation appeared to be totally
      inhibited and within 48 h of treatment, there was an extensive apoptotic
      response. Fifty percent of the cells were found in the sub-G(1) region, as
      determined by flow cytometry, and the presence of apoptotic nuclei was
      morphologically assessed by fluorescence microscopy. Caspase-3 and caspase-9
      activities were significantly elevated 24 h after seeding. At 48 h after seeding,
      caspase-3 and caspase-9 activities were further elevated and at this time point a
      significant activation of caspase-8 was also found. The DENSPM-induced cell death
      was dependent on the activation of the caspases as it was inhibited by the
      general caspase inhibitor Z-Val-Ala-Asp fluoromethyl ketone. The results are
      discussed in the light of the L56Br-C1 cells containing mutated BRCA1 and p53,
      two genes involved in DNA repair.

PMID- 11846807
TI  - Synthesis and turn-over of the replicative Cdc6 protein during the HeLa cell
      cycle.
AB  - The human replication protein Cdc6p is translocated from its chromatin sites to
      the cytoplasm during the replication phase (S phase) of the cell cycle. However,
      the amounts of Cdc6p on chromatin remain high during S phase implying either that
      displaced Cdc6p can rebind to chromatin, or that Cdc6p is synthesized de novo. We
      have performed metabolic labeling experiments and determined that [35S]methionine
      is incorporated into Cdc6p at similar rates during the G1 phase and the S phase
      of the cell cycle. Newly synthesized Cdc6p associates with chromatin. Pulse-chase
      experiments show that chromatin-bound newly synthesized Cdc6p has a half life of
      2-4 h. The results indicate that, once bound to chromatin, pulse-labeled new
      Cdc6p behaves just as old Cdc6p: it dissociates and eventually disappears from
      the nucleus. The data suggest a surprisingly dynamic behaviour of Cdc6p in the
      HeLa cell cycle.

PMID- 11846809
TI  - Domain organization, folding and stability of bacteriophage T4 fibritin, a
      segmented coiled-coil protein.
AB  - Fibritin is a segmented coiled-coil homotrimer of the 486-residue product of
      phage T4 gene wac. This protein attaches to a phage particle by the N-terminal
      region and forms fibrous whiskers of 530 A, which perform a chaperone function
      during virus assembly. The short C-terminal region has a beta-annulus-like
      structure. We engineered a set of fibritin deletion mutants sequentially
      truncated from the N-termini, and the mutants were studied by differential
      scanning calorimetry (DSC) and CD measurements. The analysis of DSC curves
      indicates that full-length fibritin exhibits three thermal-heat-absorption peaks
      centred at 321 K (Delta H=1390 kJ x mol trimer(-1)), at 336 K (Delta H=7600 kJ x
      mol trimer(-1)), and at 345 K (Delta H=515 kJ x mol trimer(-1)). These
      transitions were assigned to the N-terminal, segmented coiled-coil, and C
      terminal functional domains, respectively. The coiled-coil region, containing 13
      segments, melts co-operatively as a single domain with a mean enthalpy Delta
      Hres=21 kJ x mol residue(-1). The ratio of Delta HVH/Delta Hcal for the coiled
      coil part of the 120-, 182-, 258- and 281-residue per monomer mutants, truncated
      from the N-termini, and for full-length fibritin are 0.91, 0.88, 0.42, 0.39, and
      0.13, respectively. This gives an indication of the decrease of the 'all-or-none'
      character of the transition with increasing protein size. The deletion of the 12
      residue-long loop in the 120-residue fibritin increases the thermal stability of
      the coiled-coil region. According to CD data, full-length fibritin and all the
      mutants truncated from the N-termini refold properly after heat denaturation. In
      contrast, fibritin XN, which is deleted for the C-terminal domain, forms
      aggregates inside the cell. The XN protein can be partially refolded by dilution
      from urea and does not refold after heat denaturation. These results confirm that
      the C-terminal domain is essential for correct fibritin assembly both in vivo and
      in vitro and acts as a foldon.

PMID- 11846810
TI  - Characteristics of antenatal care attenders in a rural population in Tamil Nadu,
      South India: a community-based cross-sectional study.
AB  - The objectives of the study were to identify factors associated with utilisation
      of antenatal care facilities in a rural population in South India. A community
      based, cross-sectional questionnaire study of 30 randomly selected areas was
      used. A total of 1254 women (95%) had at least one antenatal care visit. The
      median number of visits was four. High utilisation of antenatal care facilities
      was associated with low parity and adverse obstetrical history, short distance to
      healthcare facilities and literacy. It was concluded that antenatal care coverage
      was high. Information about the above few aspects can be used to target women who
      are at risk of getting inadequate antenatal care.

PMID- 11846811
TI  - Movement and change: independent sector domiciliary care providers between 1995
      and 1999.
AB  - Promoting the development of a flourishing independent sector alongside good
      quality public services was a key objective of the community care reforms of the
      last decade. This paper charts some of the ways the independent domiciliary care
      sector is changing, as local authorities shift the balance of their provision
      toward independent sector providers and away from a reliance on in-house
      services. Two surveys of independent domiciliary care providers were carried out
      in 1995 and 1999. The aims of the studies were to describe the main features of
      provider organisations, such as size of business, client group and funding
      sources; to examine the nature of provider motivations and their past and future
      plans; to consider how local authorities manage the supply side of social care
      markets; and to examine the effects on providers of the development of the mixed
      economy. The first survey in 1995 was conducted in eight local authority areas,
      which by 1999 had increased to 11 because of the creation of three new unitary
      authorities. The findings are based on 261 postal surveys together with 111
      interviews between the two studies. The research illustrates a domiciliary care
      market that is still relatively young with many small but growing businesses.
      There are considerable differences in the split between in-house and independent
      sector services in individual authorities and a common perception among
      independent providers that in-house services receive favourable treatment and
      conditions. Spot or call-off contracts continue to be the most common form of
      contract although there are moves toward greater levels of guaranteed service and
      more sophisticated patterns of contracting arrangements. There remains an ongoing
      need to share information between local authorities and independent providers so
      that good working relationships can develop with proven and competent providers.

PMID- 11846812
TI  - Managing the entry of new medicines in the National Health Service: health
      authority experiences and prospects for primary care groups and trusts.
AB  - For the most part, the management of new medicines in the NHS has hitherto been a
      matter for local discretion. The result is that access to medicines is often
      determined by where a patient lives, as opposed to some nationally agreed
      clinical criteria. This "postcode prescribing" has led to widespread variations
      in access to medicines and concerns about the resulting inequalities. Primary
      care groups and trusts are expected to reduce variations in access to care,
      whilst at the same time balancing their finances, since any overspends on
      prescribing must be covered by disinvestment in hospital and community services.
      We interviewed 21 health authority (HA) prescribing advisers to ascertain how
      they viewed the managed entry of new medicines in order to identify lessons for
      PCGs. In addition, we report the views of local prescribing managers on the
      potential impact of recent government policy changes on the process and speculate
      on the likely implications of these for primary care groups and trusts. What is
      clear from the study is that HAs often have no explicit objective in relation to
      new medicines, but that their desire to act is prompted by fears of overspending
      on prescribing budgets. The danger of this approach is that patients may be
      denied cost-effective treatments since all new medicines are seen as a problem.
      It seems likely that PCG/Ts will face the same dilemmas with which the HA
      advisers in our study have been wrestling for some time. Recent policy changes in
      relation to prescribing budgets and new medicines are likely to exacerbate these
      problems. The tensions between local priority setting, which may mean saying no
      to new medicines, whilst at the same time eradicating postcode prescribing and
      balancing budgets means that PCG/Ts face difficult policy choices.

PMID- 11846813
TI  - Trends in informal care in Great Britain during the 1990s.
AB  - The population of adult carers in Great Britain declined during the 1990s while
      the proportion of those heavily involved in providing informal care increased.
      The intensification of care-giving was associated with an increasing number of
      caring relationships that typically make heavy demands on the carer: spouse care
      and caring for a child or parent. The provision of informal care by friends and
      neighbours diminished resulting in an overall decline in care-giving between
      households. However, parents were increasingly looked after in their own homes by
      non-resident daughters. More women than men withdrew from the less intensive care
      giving between households while more men than women took on the role of a spouse
      carer. By the end of the decade, as many men as women provided informal care for
      a spouse or partner. If the trends identified here continue beyond the study
      period, increasing resources will be required to identify heavily involved
      carers, assess their needs, and support them in their caring activities. The
      findings are based on secondary analysis of the British Household Panel Survey
      covering the years 1991-1998. As well as charting trends in the prevalence of
      informal care, changes in the locus of care, the number of care recipients, their
      relationship to their carer and the amount of time devoted to caring activities
      are described and interpreted.

PMID- 11846814
TI  - Judging the ethics of qualitative research: considering the "ethics as process"
      model.
AB  - Decision-making about the ethics of qualitative research is problematic where the
      research design is emergent, and the balance between risks and benefits for
      research subjects are difficult to ascertain prior to study implementation. The
      discourses of health/medical research ethics and those of social research are
      shown to be divergent and, furthermore, where ethics committees tie themselves to
      the health/medical model of ethical decision-making, qualitative research
      approaches can be disadvantaged. Having demonstrated the dual discourses and
      their relevance to qualitative research ethics, a critical review of current
      approaches to maximising the success of qualitative research proposals being
      considered for approval by ethics committees is undertaken. This leads to a call
      for a system of monitoring qualitative research so that the "benefit to risk"
      ratio is always on the side of benefit. This has implications for the ways in
      which ethics committees are organised and the ways in which they function.

PMID- 11846815
TI  - The use of acute hospital services by elderly residents of nursing and
      residential care homes.
AB  - The objective of this study was to compare hospitalisation rates by cause of
      admission, hospital death rates and length of stay for residents from nursing and
      residential care homes with those in the community. This is a retrospective study
      of acute hospital emergency admissions in one health district, Merton, Sutton and
      Wandsworth between April 1996 and March 1997. Data linkage and manual look up
      were used to derive emergency hospital admissions for residents of care homes
      aged 65 and over. Admission rates were calculated for cause, length of stay and
      hospital death for residents of care homes and in the community with relative
      risks. The relative risk of emergency admission from a care home compared with
      the community was 1.39 for all diagnoses, 2.68 for all injuries, and 3.96 for
      fracture of neck of femur. The relative risk of dying in hospital for care home
      residents was 2.58 overall, and 3.64 in the first 48 hours of a hospital stay
      (all P-values <0.0001). Admission rates were higher from residential than from
      nursing homes. There was some increase in admissions from homes during holiday
      periods and over Christmas. In conclusion, there are major difficulties in
      monitoring admissions from nursing and residential care homes due to poor quality
      recording and inaccuracies in NHS coding. This was compounded by an absence of
      data on the age and sex profile and healthcare needs of the resident population
      in care homes. Prospective studies are required to ascertain when admission is
      avoidable and when it is appropriate. The information strategy needs to ensure
      that routine data sources are capable of monitoring the use of hospital services
      by residents of care homes.

PMID- 11846816
TI  - The use of primary, secondary, community and social care by families who
      frequently consult their general practitioner.
AB  - There have been very few studies that have examined either the use of other
      health and social services by patients who frequently consult their general
      practitioner, or the patterns of service use of frequently attending families.
      This study has three aims: to quantify the number of contacts to primary,
      secondary, community and social services of families who frequently attend their
      general practitioner; to examine the temporal patterns of these contacts and the
      patterns of use within families; and to determine the nature of these contacts
      and how they were valued by patients and health professionals. Thirty-five
      individuals in seven families completed diaries of health service use for 8
      weeks; records from primary and community care records were analysed; health
      professionals and patients provided satisfaction scores for their contacts. The
      data were compared to standard datasets. The subjects made far more consultations
      with all health services than predicted, and less than half of these were with
      the general practitioner. Thirty-two per cent of the contacts with staff based
      within the health centre were not reported on the diary sheets. Temporal patterns
      of consulting were apparent within the families. The "index frequent attenders"
      within each family had most contacts. The differences between professional groups
      for the nature of the contact were marked, with over two-thirds of general
      practitioner contacts being for "specific symptoms or problems", and over two
      thirds of health visitor contacts being for "weight problems". These findings
      show that patients who make high use of general practitioners' services also have
      a large number of contacts for health reasons with a range of other health and
      social services. These need to be considered as an outcome measure for trials of
      intervention for frequent attendance. More work is needed to explore why some
      individuals and their families make high use of health services.

PMID- 11846817
TI  - Quality assurance in mental health-care: a case study from social work.
AB  - The quality of health and social care is now a high priority for government,
      professionals, and the public. This is particularly true of mental health, where
      explicit standards lie at the centre of current policy, demanding the development
      of reliable means for quality assurance. These need to allow for the multiplicity
      of stakeholders in mental health-care, and their different constructions of
      "quality". The challenges presented are illustrated by this account of an action
      research programme, which was developed to improve social work practice in a
      multidisciplinary mental health service, and evaluated using a case study design.
      An action research approach was chosen in preference to an "off-the-shelf"
      quality assurance system, because it possessed features that appeared to match
      the context of the work. It involved feeding back the findings of a baseline
      assessment of service quality to four teams of social workers, who used the
      information to select priority areas for improvement. An action plan was
      developed with them, and its implementation and impact were examined. Substantial
      improvements were observed in only one of the chosen target areas--the quality of
      case recording. For the other--securing the clients' full involvement in their
      care plan--very limited improvements occurred. Interview data suggested that this
      was due to the presence of extensive organisational support for the first
      objective, but not the second. These findings suggest that while some features of
      action research can contribute to quality improvement, these must be incorporated
      into a more comprehensive programme of change, which commands the support of all
      the stakeholders involved.

PMID- 11846819
TI  - Service use and needs of people with motor neurone disease and their carers in
      Scotland.
AB  - A national study of patients with motor neurone disease (MND) and their carers
      was conducted in Scotland in late 1996. A questionnaire covering areas such as:
      use of medical, social and voluntary services; use of or waiting for specialised
      equipment; satisfaction with provided services; and standard demographic data was
      used in face-to-face interviews conducted by the four Scottish Motor Neurone
      Disease Association care advisers. The care advisers also assessed the
      respondent's level of impairment, using a standard instrument: the Amyotrophic
      Lateral Sclerosis Severity Scale (ALSSS). The data was analysed using SPSS-PC. In
      total 153 people participated (response rate 92%), and as expected with this
      patient group the study recruited more men (57%) than women. Sixty per cent of
      the sample was severely disabled as measured on the ALSSS. Health services did
      not meet the needs of respondents in 19% of the cases and social services failed
      to do so according to 24% of respondents. Eighty per cent of patients with MND
      had an identified carer. Nearly four out of 10 of these carers had their sleep
      disturbed regularly, and nearly a quarter of them would have liked to have more
      help. In addition, differences were found in service provision between the East
      and West of Scotland, and consequently differences in respondent's perceptions
      about the extent to which needs were met. As found in similar studies, the formal
      health and social care sectors in conjunction with voluntary organisations are
      only partially managing the trajectory of patients with a rare progressive
      degenerative disease.

PMID- 11846820
TI  - Investigating women's preferences for intrapartum care: home versus hospital
      births.
AB  - There is an increasing amount of evidence to suggest that the clinical outcomes
      associated with a home birth for low risk women are at least as good, if not
      better than, the clinical outcomes associated with giving birth in hospital. If
      it is the case that there is little or no difference in clinical outcomes between
      the two modes of delivery, then traditional measures of benefit used in health
      economics, e.g. quality adjusted life years (QALYs), would detect little or no
      difference between the alternative modes of delivery. From this, the conclusion
      would be that the utility values associated with each mode of delivery are
      similar. However, women may still have clearly defined preferences relating to
      the way in which maternity care is provided. This paper uses the economic
      technique of conjoint analysis to assess the relative value attached to several
      main characteristics associated with the process of maternity care during the
      intrapartum stage for women who have actively chosen to give birth at home
      relative to women who have given birth in hospital. It was found that respondents
      who had chosen a home birth valued continuity of carer, a homely environment and
      the ability to make their own decisions about what happens during labour and
      delivery. In contrast, hospital birth respondents placed a relatively high value
      on access to an epidural for pain relief and not needing to be transferred to
      another location during labour if a problem arose. The results of the study
      suggest that women have clearly defined preferences for characteristics
      associated with the process of intrapartum care that would be unlikely to be
      detected by traditional benefit measures used in health economics. This finding
      is important where policy issues relating to aspects of maternity care service
      delivery are being considered.

PMID- 11846818
TI  - Awareness and understanding of dementia in African/Caribbean and South Asian
      families.
AB  - The objective of this study was to explore awareness, recognition and
      understanding of dementia symptoms in families of South Asian and
      African/Caribbean descent in the UK. In-depth, semistructured interviews were
      carried out with South Asian and African/Caribbean carers. Interview transcripts
      were analysed by coding the data into themes and investigating links between
      them, using the constant comparison approach of grounded theory. Thirty carers of
      a person with dementia of South Asian and African/Caribbean heritage were
      interviewed. Maximum variation sampling was used to include carers with a broad
      range of socio-demographic characteristics. Most participants were aware of the
      condition "dementia", but used different terms to describe the disorder. Many,
      however, had not heard of the condition before their relative developed it,
      suggesting general awareness of dementia is low. Difficulties can arise in the
      caring relationship due to a lack of understanding of the condition--in
      particular when family members place blame for the symptoms on the person with
      dementia. Conclusions of the study are that knowledge of dementia is limited, in
      terms of awareness of the condition as well as understanding of the causes. This
      research highlights the importance of raising dementia awareness and emphasises
      the importance of the provision of clear and understandable information, from
      health and social service providers.

PMID- 11846821
TI  - Needs-led assessment: the challenges and the reality.
AB  - The NHS & Community Care Act 1990 heralded a new era in community care in the UK.
      Needs-led assessment and case management were to form the cornerstone of high
      quality care. Practitioners were challenged to alter their attitudes and practice
      to accommodate the needs-led approach. Previously they had assessed need to
      ascertain eligibility for statutory services, now they were required to identify
      "need" per se. The pivotal role given to assessment meant the success, or
      otherwise, of the reforms lay in part on the ability of practitioners to make
      this transition. However, to make needs-led assessment a reality, practitioners
      would have both to overcome conceptual barriers--need being an unclear concept,
      with no clear framework existing to assess need--and also to deal successfully
      with the conflicting requirement to ration services. In order to investigate
      whether the shift to needs-led practice had been possible, the opinions of social
      and healthcare practitioners providing services for older people in North Wales
      were sought through semi-structured interviews in 1994-1995 and 1998-1999.
      Supports and constraints to practice were also explored. Practitioners indicated
      that whilst they welcomed the needs-led philosophy, putting it into practice was
      difficult, if not impossible. The main constraints were a lack of resources
      (financial, service provision and staffing) and the conceptual difficulty of
      separating "need" from the "need for a particular service". Ever-tightening
      budgets and service eligibility criteria over the period of the study indicate
      that a shift of focus from assessment of need to rationing has taken place.

PMID- 11846822
TI  - The cost effectiveness of specialised facilities for service users with
      persistent challenging behaviours.
AB  - Little systematic research relates specifically to the last people to leave a
      psychiatric hospital at the end of a closure programme. The long-running
      evaluation of the reprovision of services from Friern Hospital in North London
      allowed a special study to be made of such a group (67 people in all), whose
      range of problem behaviours made placement in community settings most difficult.
      The patients were relatively young, with a shorter length of stay than the
      remainder of the former long-stay hospital population. They were assessed three
      times: before leaving Friern, and one and 5 years after relocation. The social
      and clinical characteristics of each person were measured, and the full costs of
      their care calculated. The "difficult-to-place" patients moved to four highly
      staffed rehabilitation facilities, where the total cost of their care was, on
      average, 1230 UK pounds per week. There was no overall change in their
      psychiatric state over the 5 years after they left Friern Hospital although, in
      the longer-term, they gained skills in several areas of daily functioning. Most
      importantly, there was a fall of almost 50% in the number of challenging
      behaviours exhibited by the study group. At the five-year follow-up point, the
      cost of care had fallen, on average, by 170 UK pounds per week, and 24 people had
      been able to move to more independent accommodation arrangements. Study
      participants had gained a new network of community service contacts, and used
      services provided by a greater variety of agencies. The indicators suggest that
      high expenditure on alternative care was justified retrospectively by overall
      long-term outcomes. An important policy lesson from the Friern Hospital
      reprovision study is that adequate funds should be reserved until the end of the
      closure programme to allow the investment of resources in provision for patients
      with the most severe problem behaviours.

PMID- 11846823
TI  - The responsibility to care for single homeless people.
AB  - This paper examines the reasons why in contemporary Britain many single homeless
      people with severe physical and mental health problems and welfare needs do not
      receive the treatment, care and financial support that they manifestly need, and
      in particular considers the interaction between their personal characteristics
      and the organisation and the obligations of services. Homelessness is a complex
      concept associated with problems of housing, health, social care and income. The
      greatest weaknesses of the service system are that no single agency has a
      statutory responsibility to ensure that vulnerable homeless people are served,
      and none of the generalist welfare agencies have a duty to seek out those who do
      not present. As a result, single homeless people fall between the housing, health
      and social services and amass exceptional unmet needs. The paper appraises the
      approaches to single homeless people's problems that have recently been
      introduced by the Rough Sleepers' Unit (RSU), and discusses the ways in which
      current reforms of the welfare services may impact on the situation of homeless
      people. With the possibility that the RSU's prime responsibility for
      commissioning single homeless people's services will transfer to local
      authorities in 2002, the paper concludes by specifying the implications for
      voluntary and statutory providers and makes recommendations about the attribution
      of the responsibility to care for this vulnerable group.

PMID- 11846824
TI  - Barriers to healthcare access in a non-elderly urban poor American population.
AB  - An understanding of perceived barriers to health-care is critical to improving
      healthcare access for all Americans. To determine perceived barriers to health
      care in an urban poor population in Dayton, Ohio, a face-to-face door-to-door
      survey of individuals identified through targeted, stratified, area probability
      sampling was done. A sample of 413 non-elderly poor adults, including 19% without
      telephones, reported personal relevance of various barriers to healthcare access.
      Most frequently endorsed barriers were lack of information about free or reduced
      cost health-care, anticipated cost, and difficulty accessing child-care. Seventy
      four per cent of respondents reported more than one barrier. Individuals without
      telephones and those without health insurance reported more barriers to health
      care. Reported barriers were similar for working and non-working poor, except for
      transportation problems, more frequently reported by non-working respondents.
      This study provides important data on what poor people in a medically underserved
      community perceive to be barriers to accessing health-care and underscores the
      importance of including people without telephones in the study design.
      Respondents who did not have telephones were more likely to report multiple
      barriers, particularly problems with lack of information about free or discounted
      medical care, child-care, and transportation. These findings suggest the
      importance of door-to-door surveys rather than telephone surveys for getting
      accurate data on the poor.

PMID- 11846825
TI  - The emotional climate of care-giving in home-care services.
AB  - The emotional aspects of the care-giving relationship in home-care services are
      studied, starting from the home-care recipients' and the home-care workers'
      perception of the emotional climate. Their experiences of the care-giving
      relationship and the influence from different aspects of the care-giving
      situation and social processes in the work organisation are explored. Two hundred
      and twenty-two recipients and their home-care workers in three typical Swedish
      municipalities were studied. The emotional climate is described with the help of
      a scale of 85 adjectives. Results show that home-care workers are more likely to
      experience the climate with a higher degree of emotionality. There is symmetry
      between the parties in the perception of a negative climate. However, if one
      party perceives the climate as close the other party is more likely to perceive
      it as rational or instrumental. The organisational processes, especially the
      group climate of the work team, principally influence the home-care recipients'
      perceptions. The workers' perceptions are principally influenced by age and
      gender of the recipients and the workers' own age. The emotional climate is
      constructed in a process between the parties, depending on their responses to
      each other. Tendencies to perceive a specific climate are strengthened or
      weakened by context variables and this in turn changes the care-giving
      interaction.

PMID- 11846827
TI  - User focus groups and Best Value in services for people with learning
      disabilities.
AB  - This paper examines the problems and potentials of employing user focus groups as
      part of an approach to defining and reviewing Best Value in local authority and
      jointly commissioned services for people with learning disabilities. Drawing on
      experience from three local authority initiatives and wider experience with Best
      Value, the paper describes the development of user focus groups for helping
      review adult placement, outreach and day services for people with learning
      disabilities. The key methodological considerations for consulting with service
      users with learning disabilities through focus groups are identified and the
      interpretation of outcomes considered. The paper concludes with pointers for the
      effective operation of user focus groups in local authority Best Value reviews of
      services for people with learning disabilities, of use to practitioners, service
      managers and commissioners.

PMID- 11846826
TI  - Informal carers of cancer patients: what are their unmet psychosocial needs?
AB  - This paper considers the significant unmet psychosocial needs of the informal
      carers of cancer patients, drawing on data generated in a 3-year UK study (1997
      2000) on the psychosocial needs of cancer patients and their main carers. While
      the needs of the carers of cancer patients are increasingly being recognised in
      healthcare policy documents, there is relatively little published literature on
      these needs. A "significant unmet need" is defined here as a need deemed
      important by the carer, but which has not been met. A descriptive cross-sectional
      survey of carers was conducted and the responses of 195 carers relating to 48
      psychosocial need items were analysed. A subset of these carers (n = 32) were
      interviewed. Forty-three per cent of carers had significant unmet needs. They
      were more likely to be those where the relationship to the patient was not that
      of a partner or spouse, more likely to have other caring responsibilities, and
      less likely to have friends or relations to call upon for help. Carers with unmet
      needs were also more likely to be in poor health themselves or to be caring for a
      patient who had reached the palliation-only phase in their cancer journey. The
      majority of carers expressed the importance of needs such as having good
      relationships with healthcare professionals and receiving honest information, but
      few expressed dissatisfaction with these aspects of need. Items of significant
      unmet need clustered around aspects of managing daily life, emotions, and also
      social identity for a sizeable minority of carers. These are the same areas of
      significant unmet need that concern patients. However, carers have more of these
      concerns, reflecting their comparative neglect. The paper also considers how
      these widespread concerns can be addressed.

PMID- 11846828
TI  - Absent voices compromise the effectiveness of nursing home regulation: a critique
      of regulatory reform in the UK nursing home industry.
AB  - Over the last decade there has been consistent pressure for the healthcare
      services in the UK to become more accountable to users. Now over half the
      healthcare beds in England are in the privatised nursing home sector, and
      regulation of the sector is under reform. Yet requirements for user
      accountability have not been reflected in these reforms. In other sectors,
      consumer involvement in regulatory agencies and processes is seen as important to
      the success of the regulatory enterprise. But in the care sector neither users
      nor their representatives have been given legal rights of involvement in the
      National Care Standards Commission or in regulatory processes. This paper argues
      that failure to involve users not only places the regulation enterprise at risk
      of capture by the industry, but will also weaken the legitimacy of the new
      Commission.

PMID- 11846829
TI  - Evaluation of community mental health services: comparison of a primary care
      mental health team and an extended day hospital service.
AB  - Alongside mental health policies emphasising the need to focus on people
      experiencing serious, long-term problems, recent general healthcare policy is
      leading to the development in the UK of a primary care-led National Health
      Service. While most primary care-led mental health initiatives have focused on
      supporting general practitioners (GPs) in managing milder depression and anxiety,
      this article describes an evaluation comparing primary care-based and secondary
      care-based services for people with serious long-term problems. A survey of
      service users was carried out at three points in time using three measures: the
      Camberwell Assessment of Need, the Verona Satisfaction with Services Scales and
      the Lancashire Quality of Life Profile. Staff views were sought at two time
      intervals and carers' views were obtained towards the end of the 2-year study
      period. The results indicate that both services reduced overall needs and the
      users' need for information. The primary care service also reduced the need for
      help with psychotic symptoms whereas the secondary care service reduced users'
      need for help with benefits and occupation. There were no major differences in
      terms of satisfaction or quality of life. Primary care-based services therefore
      appear to have the potential to be as effective as more traditional secondary
      care services. However, a more comprehensive range of services is required to
      address the whole spectrum of needs, a conclusion supported by the views of staff
      and carers.

PMID- 11846837
TI  - Inhibition of tumour invasion and angiogenesis by epigallocatechin gallate
      (EGCG), a major component of green tea.
AB  - Epidemiological studies have suggested that consumption of green tea may decrease
      cancer risk. In addition, abundant pre-clinical data from several laboratories
      have provided convincing evidence that polyphenols present in green tea afford
      protection against cancer in both in vivo and in vitro studies. Recently,
      epigallocatechin gallate (EGCG), a putative chemopreventive agent and a major
      component of green tea, was reported to inhibit tumour invasion and angiogenesis,
      processes that are essential for tumour growth and metastasis. Understanding the
      basic principles by which EGCG inhibits tumour invasion and angiogenesis may lead
      to the development of new therapeutic strategies, in addition to supporting the
      role of green tea as a cancer chemopreventive agent.

PMID- 11846838
TI  - The effect of IFNgamma on the hepatocyte: cell cycle and apoptosis.
AB  - The inflammatory cytokine interferon gamma (IFNgamma) can cause cell cycle arrest
      and apoptosis in the hepatocyte. Primarily these processes are protective but in
      chronic liver disease oncogenic mutations may prosper. IFNgamma signalling is
      discussed showing how p53 is induced to cause cell cycle arrest. While caspases
      are are known to be responsible for IFNgamma induced apoptosis, how they are
      activated is unclear. Potential mechanisms are reviewed.

PMID- 11846839
TI  - TNF-alpha is expressed at sites of parasite and tissue destruction in the spleen
      of mice acutely infected with Trypanosoma cruzi.
AB  - Mice infected with a macrophagotropic strain of Trypanosoma cruzi develop
      progressive splenomegaly due to reactive hyperplasia with increased number of
      lymphocytes and macrophages, culminating in parasite disintegration and necrosis
      of parasitized cells. Necrotic changes have been attributed to the liberation of
      toxic cytokines, including TNF-alpha, from parasitized macrophages. In the
      present study, the presence of TNF-alpha was investigated in situ. In addition
      the participation of destroyed parasites in inducing the liberation of TNF-alpha
      was examined in two highly susceptible mice strains (C3H and Swiss) and a more
      resistant strain (DBA). Swiss (90) C3H/He (83) and DBA (30) mice were infected
      with the Peruvian strain of T. cruzi. Nineteen infected Swiss mice, and 22
      infected C3H/He were treated with Benznidazole (one or two doses, 100 mg/kg
      bw/day), on the 8th and 9th days after infection. Necrotic splenic lesions
      occurred in both susceptible and resistant strains of mice. Although differing in
      degree, lesions were more intense in C3H and Swiss than in DBA mice. Comparing
      untreated and treated susceptible mice, necrotic lesions were significantly less
      intense in the latter. By specific monoclonal antibody immunolabelling, TNF-alpha
      was demonstrated in the cytoplasm of macrophages and within necrotic areas, from
      Swiss, C3H/He and DBA mouse spleens. In conclusion, TNF-alpha, probably
      synthesized by macrophages, was strongly expressed at the sites of parasite and
      cell destruction, thus appearing to play a pivotal role in splenic necrotic
      changes associated with severe experimental T. cruzi infection.

PMID- 11846841
TI  - British Society for Matrix Biology meeting, Manchester, 2-3 April 2001.
      Abstracts.

PMID- 11846842
TI  - Chlorhexidine varnishes: a review.
AB  - BACKGROUND: Of all chemical plaque control agents, chlorhexidine digluconate has
      proven to be the most effective and safe. Since 1964, varnishes have been used
      for local delivery of fluor and are reported to be an effective and easy to use
      vehicle. During the past decade, varnishes for local delivery of antimicrobial
      agents have been developed and investigated in vitro and in vivo. AIM: In this
      paper, the existing literature on the use of 3 different chlorhexidine varnishes
      in different fields in dentistry is reviewed. METHOD: In vitro results concerning
      the release of the antimicrobial agents are compared for the 3 different varnish
      formulations. RESULTS AND CONCLUSION: Clinical reports on the efficacy of
      controlled-release systems in altering cariogenic and periodontopathic microflora
      are summarized.

PMID- 11846843
TI  - Some effects of enamel matrix proteins on wound healing in the dento-gingival
      region.
AB  - OBJECTIVE: The aim of the present study was to evaluate by clinical means the
      effect of enamel matrix proteins on the healing of a soft tissue wound produced
      by periodontal pocket instrumentation. MATERIAL AND METHODS: The study was
      performed as an intra-individual, longitudinal trial of 3 weeks duration with a
      double-masked, split-mouth, placebo-controlled and randomized design. The patient
      material was comprised of 28 subjects with moderately advanced, chronic
      periodontitis. Each patient presented with 3 sites in each of 2 jaw quadrants
      with a probing pocket depth (PPD) of >or=5 mm and bleeding following pocket
      probing (BoP). Baseline examination, including assessments of plaque, gingival
      inflammation, PPD, BoP and root dentin sensitivity, was carried out one week
      after oral hygiene instruction and careful self-performed plaque control. All
      experimental sites were scaled and root planed, and the soft tissue wall of the
      pocket was curetted to remove the pocket epithelium and adjacent granulation
      tissue. The site was carefully irrigated with saline. When the bleeding from the
      pocket had ceased, a 24% EDTA gel was applied in the site and retained for 2 min.
      This was followed by careful irrigation with saline. Left and right jaw quadrants
      were then randomized to subgingival application of enamel matrix derivative
      (Emdogain) or vehicle-control. All sites were re-examined after 1, 2 and 3 weeks.
      In addition, a visual analogue scale (VAS) was used to score the degree of post
      treatment discomfort. The primary endpoints of treatment success were defined as
      (i) pocket closure (PPD <or=4 mm), (ii) no bleeding following pocket probing,
      (iii) no sign of gingival inflammation (GI score =0) and (iv) low degree of post
      treatment discomfort (VAS <or=20). Statistical analyzes of intra-individual
      differences between the test and control treatments were performed by the use of
      Wilcoxon signed rank test. For comparison of the proportions of sites reaching
      the defined endpoints of treatment success, a site-based analysis was performed
      using 2x2 tables and the Fisher exact test. RESULTS: The endpoint "GI score =0"
      was reached at 16% of the sites subjected to application of Emdogain at 1 week
      and at 2% of the control sites (p=0.001). At 2 weeks, the corresponding figures
      were 25% versus 12% (p =0.028). Absence of BoP was at 1 week 57% for the Emdogain
      treated sites compared to 35% for the control sites (p=0.003). At 2 weeks, this
      endpoint was reached in 73% and 59% of the test and control sites, respectively
      (p=0.051). In terms of the endpoint defined for probing pocket depth, PPD <or=4
      mm, no differences between test and control sites were found. At 1 week, the
      proportion of patients reporting a VAS score <or=20 was significantly higher for
      the Emdogain treated quadrants than for controls (p=0.002). CONCLUSION: The
      results indicated that Emdogain topically applied in instrumented pockets enhance
      the early healing of periodontal soft tissue wounds.

PMID- 11846840
TI  - Ultrastructure of Purkinje cell perikarya and their dendritic processes in the
      rat cerebellar cortex in experimental encephalopathy induced by chronic
      application of valproate.
AB  - Long-term intragastric administration of the antiepileptic drug sodium valproate
      (Vuprol Polfa) to rats for 1, 3, 6, 9 and 12 months, once daily at the effective
      dose of 200 mg/kg body weight showed morphological evidence of encephalopathy,
      manifested by numerous nonspecific changes within Purkinje cell perikarya and
      their dendritic processes. The first ultrastructural abnormalities appeared after
      3 months. They became more severe in animals with longer survival and were most
      pronounced after 12 months. The changes were maintained both 1 and 3 months after
      drug withdrawal. Mitochondria of Purkinje cell perikarya were most severely
      affected. Damage to mitochondria was accompanied by disintegration and
      fragmentation of granular endoplasmic reticulum, dilation of channels and
      cisterns of Golgi apparatus, enlargement of smooth endoplasmic reticulum elements
      including submembranous cisterns, and accumulation of profuse lipofuscin
      deposits. Frequently, Purkinje cells appeared as dark ischemic neurones, with
      focally damaged cellular membrane and features of disintegration. Swollen
      Bergmann's astrocytes were seen among damaged Purkinje cells or at the site of
      their loss. The general pattern of submicroscopic alterations of Purkinje cell
      perikarya suggested severe disorders in several intercellular biochemical
      extents, including inhibition of oxidative phosphorylation and abnormal protein
      synthesis, both of which could lead to lethal damage. Ultrastructural
      abnormalities within dendrites were characterized by damage to elements of smooth
      endoplasmic reticulum, which was considerably enlarged, with formation of large
      vacuolar structures situated deep in the dendroplasm. Mitochondrial lesions and
      alterations in cytoskeletal elements--disintegration of microtubules or even
      their complete loss--were also observed. The general pattern of abnormalities
      within the organelles and cytoskeletal elements of dendritic processes in
      Purkinje cells in the VPA chronic experimental model imply that there are
      disturbances in detoxication processes. Furthermore these changes were
      irreversible, as they were maintained after drug withdrawal.

PMID- 11846844
TI  - Prostaglandin E2 concentrations in gingival crevicular fluid: observations in
      untreated chronic periodontitis.
AB  - OBJECTIVES: We set out to monitor gingival crevicular fluid prostaglandin E2 (GCF
      PGE2) concentrations longitudinally in a cohort of subjects with chronic
      periodontitis, given that we had noted an unexplained trend for GCF-PGE2
      concentrations to gradually increase in control groups and placebo populations in
      previously published clinical trials. MATERIAL AND METHODS: 41 adults with
      moderate-severe chronic periodontitis were recruited. GCF samples were collected
      from 8 test sites (with 5-8 mm probing depths and attachment loss) every 30 days
      for 150 days, and assayed for PGE2. Clinical measurements (probing depths,
      attachment levels, bleeding on probing) were recorded at days 0 and 150. RESULTS:
      A gradual and statistically significant increase in GCF-PGE2 concentrations was
      observed over the course of the study, from 40.3 ng/ml to 83.1 ng/ml (p<0.001).
      When data were expressed as absolute PGE2 content, a similar statistically
      significant increase from baseline to day 150 was observed (p<0.001). GCF volumes
      did not vary significantly during the study (p>0.05). Over the same time period,
      no statistically significant changes in clinical parameters were recorded, with
      the exception of mean probing depths, which decreased slightly from 5.73 mm to
      5.51 mm (p<0.05). CONCLUSION: A trend for gradually increasing GCF-PGE2
      concentrations in the absence of any clinical signs of disease progression was
      noted in a group of patients monitored longitudinally. We suggest that this
      phenomenon is to be expected in longitudinal clinical trials, and propose a new
      model for the role of PGE2 in the pathogenesis of periodontal destruction. We
      feel that if GCF mediators are to be monitored in clinical studies, then both
      concentrations and absolute mediator content should be calculated, and a
      standardised sampling protocol should be employed.

PMID- 11846845
TI  - Association between bone loss in periodontal disease and polymorphism of N
      acetyltransferase (NAT2).
AB  - BACKGROUND: The individual susceptibility to periodontal disease is probably the
      result of an interaction of multiple genetic and environmental influences.
      Polymorphism of the N-acetyltransferase (NAT 2) modifies the individual
      susceptibility to toxicity from certain therapeutic drugs or heterocyclic amines
      including substances from cigarette smoke. Subjects are to be classified as
      'slow' or 'rapid' acetylators according to how fast their bodies metabolise such
      xenobiotics. Differences in their ability to detoxify these substances may
      contribute to an increased risk for periodontitis in subjects exposed to
      cigarette smoke or other xenobiotics. OBJECTIVE: The purpose of this study was to
      assess whether the NAT2 genotype is a risk factor for periodontal disease in
      Caucasian patients suffering from adult periodontitis. MATERIAL AND METHODS: 154
      Caucasian subjects were assigned to one of the 3 groups: no, moderate, and severe
      periodontal disease based on bone and attachment loss. In all subjects,
      genotyping for mutations on the N-acetyltransferase (NAT2) gene was performed by
      means of PCR and RFLP analysis. RESULTS: Comparison of frequency distribution of
      NAT2 acetylation types between the most diseased group and not or moderately
      affected subjects showed a tendency to over-representation of slow acetylators
      with severe disease. When using bone loss as measure of periodontitis, this over
      representation shows a significant association with the disease (odds ratio=2.13,
      p=0.025). In the logistic regression analysis, adjusted for age and smoking, NAT2
      slow phenotype was significantly associated with the severity of bone loss, the
      odds ratio being 2.09 (95% C.I. 1.02-4.26, p=0.043). In a case-control analysis
      (controlled for smoking, gender and age) mean bone loss showed a significant
      difference between the 2 NAT2-type groups (Mann-Whitney test p=0.041).
      CONCLUSION: The data suggest that the slow acetylator phenotype may be associated
      with a higher risk of periodontitis, especially in smokers. Possible explanations
      regarding the mechanism are discussed; however, such attempts are highly
      speculative at this time.

PMID- 11846846
TI  - Tumor necrosis factor-alpha gene polymorphisms in relation to periodontitis.
AB  - BACKGROUND: Genetic polymorphisms for cytokines have been proposed as potential
      genetic markers for destructive periodontal disease. The present aim was to
      investigate 4 bi-allelic polymorphisms in the TNF-alpha gene in relation to
      susceptibility for and severity of periodontitis. The polymorphisms were all
      transitions from G to A, 3 in the promoter positions: -376, -308, -238; and one
      in the first intron at position +489. METHODS: 90 periodontitis patients and 264
      reference control subjects were genotyped and frequencies of genotypes and
      alleles were analyzed. Also genotype frequencies among severe and moderate
      periodontitis patients were explored, and the % of teeth with 50% bone loss and
      the % of teeth without any bone loss for patients with the A allele (A+ genotype)
      and patients without (A- genotype) were compared. RESULTS: The distributions of
      genotypes and frequencies of A allele carriage rates for the 4 TNF-alpha
      polymorphisms were not different between patients and reference controls; Hardy
      Weinberg equilibrium criteria were fulfilled. Also the distribution of A+ and A-
      genotypes, alone or in combinations, were not different for severe periodontitis
      compared to moderate periodontitis patients. None of the A+ genotypes showed a
      significant different bone loss pattern compared to A- genotype patients. Smoking
      status of the patients did not influence the results. CONCLUSIONS: Genetic
      polymorphisms in the TNF-alpha gene at positions -376, -308, -238 and +489 could
      not be identified as susceptibility or severity factors in periodontitis,
      irrespective of the smoking status of the patients.

PMID- 11846847
TI  - Comparative study of Emdogain and coronally advanced flap technique in the
      treatment of human gingival recessions. A prospective controlled clinical study.
AB  - OBJECTIVES: Various surgical techniques have been proposed for coverage of
      denuded root surfaces. The aim of this study was to evaluate a comparison of
      coronally repositioned flap procedure with or without the use of enamel matrix
      proteins in the treatment of recession defects. MATERIAL AND METHODS: This study
      was an intra-individual longitudinal test of 12 months duration conducted as a
      blinded, split-mouth, placebo-controlled and randomised design. It was performed
      in 2 dental schools. 36 patients, aged 22-62 years, with 2 paired buccal
      recession defects of at least 3 mm participated. Surgical recession coverage was
      performed as coronally-advanced flap technique at both sites in the same session.
      One site was additionally treated with commercially-available enamel matrix
      proteins (Emdogain) and the other site with placebo (propylene glycol alginate)
      in accordance with the randomisation list. A blinded examiner assessed pre- and
      post-surgical measurements. Clinical measurements and photographs were taken pre
      surgically and after 1 week, 3 weeks, 3 months, 6 months and 12 months,
      postoperatively. Measurements comprised height and width of the gingival
      recession, height of keratinized tissue, probing attachment level, probing pocket
      depth and alveolar bone level by periodontal probe, Florida Probe or caliper to
      the nearest 0.5 mm. RESULTS: 12 months after therapy, both treatment modalities
      showed significant root coverage and probing attachment gain. Gingival recession
      decreased from 3.7 mm to 0.8 mm for the Emdogain treated sites and from 3.9 mm to
      1.0 mm for the control sites, corresponding to mean root coverages of 80% and
      79%, respectively. This difference was not significant. With the exception of
      keratinized tissue gain, which was significantly higher (p=0.003) in the Emdogain
      group, all other clinical variables were not different in the between-group
      comparison. CONCLUSIONS: As the additional use of Emdogain together with
      coronally advanced flap technique for recession coverage showed no difference in
      the overall clinical outcome, there is no clear benefit to combine Emdogain with
      this surgical technique.

PMID- 11846848
TI  - Testing the efficacy of 2 prototype brush heads for a powered toothbrush:
      refining the model.
AB  - OBJECTIVES: To compare 2 prototype powered toothbrush (PTB) heads (A, B) to a
      marketed head (Sensiflex 2000) for plaque removing efficacy on the Philips/Jordan
      HX2550 PTB. MATERIALS AND METHODS: A 2-week, 3-group, single-blind trial
      recruited 78 volunteers (18-25). Plaque indices (PIs) were recorded at screening
      and 14 days later at baseline. Subjects were stratified (gender and PI) and then
      asked to abstain from oral hygiene measures for 48 h. A supervised episode of
      brushing with the allocated PTB head followed. Subjects then used the PTBs at
      home for the next 12 days before being asked to abstain from all oral hygiene
      measures for another 48 h prior to a second supervised brushing episode. Plaque
      was scored using a new modification of the Quigley & Hein Index (PI) at full
      mouth (FM), interproximal (IP) and smooth surfaces (SS). PIs were recorded before
      and after the supervised brushing episodes to enable the means of the within
      subject differences (pre- to post-brushing) to be compared between groups
      (ANOVA/t-tests). RESULTS: There were no significant differences in PI between
      groups at baseline or prior to the supervised brushings (p>0.05). Highly
      significant, mean reductions in PIs (approximately 1/2 of one PI unit) were
      observed for design B compared with the Sensiflex 2000 at FM and IP sites
      (p<0.0001) for both supervised brushing episodes. A significant reduction in PI
      at SS was seen only after the first brushing episode (p=0.0004). For design A, PI
      reductions were consistently greater than those for the Sensiflex 2000 but
      differences were only significant at the p<0.05 level. CONCLUSION: It is
      concluded that this model of clinical trial has sufficient power to demonstrate
      clinical superiority with respect to plaque removal for PTBs and can be used for
      testing one or more prototype designs of brush heads.

PMID- 11846849
TI  - GCF IL-1beta profiles in periodontal disease.
AB  - OBJECTIVES: Studies suggest a genetic influence on levels of interleukin-1beta
      (IL-1beta) in gingival crevicular fluid (GCF). Levels of IL-1beta in GCF,
      however, are also dependent upon the clinical parameters at the site of
      collection, including probing depth (PD) and level of attachment (AL). To examine
      this issue, IL-1beta in GCF was evaluated from patients with varying degrees of
      periodontal disease. The influence of both the status of the patient and the
      probing depth at the sampled sites were considered in the analysis. MATERIAL AND
      METHODS: GCF IL-1beta was determined by ELISA at 6-8 molar sites from 29 non
      smoking adults with mild, moderate, or severe periodontal disease at baseline, 2
      weeks, and 24 weeks following scaling and root planing. For later analysis,
      patients were dichotomized on the basis of disease severity (mild/moderate vs
      severe). Sampled sites were classified at baseline by PD as, shallow (<4 mm),
      intermediate (4-6 mm), or deep (>6 mm). RESULTS: PD and AL were each strongly
      correlated with IL-1beta levels at baseline. However, patients with severe
      disease had higher levels of IL-1beta in each PD category than those with
      mild/moderate disease. As compared to patients with mild/moderate disease, IL
      1beta levels in shallow sites from patients with severe disease was elevated
      nearly 2 fold (p<0.001). IL-1beta levels were reduced in all groups at 2 weeks
      and were still significantly reduced in patients with mild/moderate disease at 24
      weeks. At 24 weeks IL-1beta returned to near baseline levels in patients with
      severe disease. CONCLUSION: While PD and AL are each associated with increased
      GCF IL-1beta, patients with severe disease show higher IL-1beta GCF levels in
      shallow sites, suggesting that high GCF IL-1beta expression is in part a host
      trait, and not strictly a function of clinical parameters.

PMID- 11846850
TI  - A double-blind placebo-controlled trial of azithromycin as an adjunct to non
      surgical treatment of periodontitis in adults: clinical results.
AB  - BACKGROUND/AIMS: The aim of the study was to investigate the clinical and
      microbiological effects of azithromycin as an adjunct to the non-surgical
      treatment of periodontitis in adults. Azithromycin is an antibiotic which is
      taken up by phagocytes and is released over long periods in inflamed tissue but
      requires a total of only three doses of 500 mg to produce its therapeutic effect.
      METHOD: 46 patients were treated in a double-blind placebo-controlled study with
      assessments at weeks 0, 1, 2, 3, 6, 10 and 22. Throughout the trial measurements
      were made of plaque, gingival bleeding, calculus, probing pocket depths and
      bleeding on probing. Microbiological sampling was carried out from a selected
      pocket >or=6 mm at each visit. The regime employed consisted of OHI, scaling and
      root planing at weeks 0, 1 and 2 with reinforcement of OHI and minimal scaling at
      weeks 6, 10 and 22. Patients were randomly assigned to receive either
      azithromycin, (A), or placebo capsules, (C), 500 mg, 1x daily for 3 days at week
      2. 44 patients completed the study. Mean pocket depths were analysed using
      analysis of covariance in 3 groups with initial pocket depth values of 1-3 mm, 4
      5 mm and >or=6 mm. RESULTS: The results of the microbiology have been reported in
      a separate paper. The clinical data showed that by week 22 a lower % of pockets
      initially >5 mm deep remained above that level in the 23 patients taking
      azithromycin (A), than the 21 taking the placebo (C), (A, 5.6%; C, 23.3%). Also
      at week 22, for pockets initially 4 mm or more, the test group had fewer pockets
      >3 mm deep (A, 26.1%; C, 44.3%), fewer failing to improve in probing depth (A,
      6.6%; C, 21.6%) and fewer continuing to bleed on probing (A, 46.9%; C, 55.6%)
      when compared with the control group. Pocket depths initially 4-5 mm or 6-9 mm
      analysed by analysis of covariance showed lower mean pocket depths in the
      patients on azithromycin, at weeks 6, 10 and 22, (pockets initially 4-5 mm,
      p<0.001 on all occasions, pockets initially 6-9 mm, p<0.001, week 6; p< 0.003,
      week 10; p<0.001, week 22). CONCLUSIONS: Azithromycin may be a useful adjunct in
      the treatment of adult periodontitis, particularly where deep pockets are
      present.

PMID- 11846851
TI  - Effect of the enamel matrix derivative Emdogain on the growth of periodontal
      pathogens in vitro.
AB  - OBJECTIVES: The aim of this study was to evaluate the effect of Emdogain (EMD),
      used for periodontal regeneration, on the growth of periodontal pathogens like
      Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis and Prevotella
      intermedia. For comparison, we studied the effect of EMD on several microbes
      associated with other oral diseases as well as its effect on non-pathogenic oral
      inhabitants. METHODS: Freshly prepared EMD or its vehicle propylene glycol
      alginate (PGA) alone were added to calibrated suspensions of microbes. As a
      control, imitating the post-surgical subgingival situation after flap closure, a
      serum/NaCl-solution mixture was used. Aliquots for growth assays were taken at
      scheduled times for calculation of colony-forming units and cell densities over
      an observation period of 24 h. Additionally, EMD was spotted onto selected, newly
      seeded microbes growing on agar plates to see if growth inhibition zones could be
      produced. RESULTS: The study revealed a marked inhibitory effect of EMD on the
      growth of the gram-negative periodontal pathogens. A. actinomycetemcomitans
      showed a significant decrease (p=0.012) in viable counts after 24 h when EMD was
      added at baseline. P. gingivalis and P. intermedia also showed a marked growth
      reduction in the presence of EMD and in these cultures no viable microbes could
      be detected anymore after 24 h. In contrast, no significant growth inhibition was
      observed in gram-positive bacteria. CONCLUSIONS: The results suggest that EMD has
      a positive effect on the composition of bacterial species in the post-surgical
      periodontal wound, by selectively restricting growth of periopathogens that could
      hamper the wound healing and reduce the outcome of regenerative procedures.

PMID- 11846852
TI  - Antimicrobial effects of 2.94 microm Er:YAG laser radiation on root surfaces: an
      in vitro study.
AB  - OBJECTIVES: This in vitro study investigated the antimicrobial effects of 2.94
      microm Er:YAG laser radiation on root surfaces. MATERIALS AND METHODS: The study
      used 125 extracted teeth which were divided into 2 groups (A, B) of 40 teeth and
      3 groups of 15 teeth (C, D, E). A defined and similarly-sized area of the root
      surface was inoculated with an aliquot of 7 microl of a bacterial suspension of
      Escherichia coli (ATCC 25922), Staphylococcus aureus (ATCC 25923), Actinobacillus
      actinomycetemcomitans (ATCC 43719), Eikenella corrodens (ATCC 51724), or
      Peptostreptococcus micros (ATCC 33270). Subsequently, the samples from each group
      were further divided into subgroups which have been irradiated either with 55,
      75, and 105 (group A, B) or 55 and 75 (group C, D, E) laser pulses. 1 subgroup of
      each group was left untreated as control. The source of laser radiation was an
      Er:YAG laser emitting pulsed infrared radiation at a wavelength of 2.94 microm.
      The number of bacteria was determined using the surface spread plate technique.
      The statistical analysis was performed using ANOVA followed by the Scheffe-test.
      RESULTS: Depending on the number of laser pulses the bacterial load in the E.
      coli group was reduced by the Er:YAG laser radiation after exposure to 105 laser
      pulses to 5.5% of the initial count and that in the Staph. aureus group to 15.1%.
      The number of bacteria in case of A. actinomytemcomitans was reduced to 8.3%, in
      case of E. corrodens to 3.0% and in case of P. micros to 22.0% after application
      of 75 laser pulses. CONCLUSION: Besides the selective removal of plaque and
      calculus, the 2.94 microm Er:YAG laser radiation causes reduction in bacteria on
      root surfaces.

PMID- 11846853
TI  - Application of an adjusted chi2 statistic to site-specific data in observational
      dental studies.
AB  - BACKGROUND: When a binary response is observed on teeth from each subject
      belonging to 2 or more exposure groups, application of the usual Pearson chi2
      tests is invalid, since such responses within the same subject are not
      independent. Consequently, special statistical methods are needed to control for
      the correlation among teeth (sites) within the same subject. A simple adjustment
      to the Pearson chi2 statistic has been proposed for comparing proportions in site
      specific data. However, the required assumptions for this statistic have not yet
      been thoroughly addressed. These assumptions are guaranteed to hold in
      experimental comparisons, but may be violated in some observational studies.
      METHOD: We investigate the conditions under which the adjusted chi2 statistic is
      valid and examine the performance of the adjusted chi2 statistic when these
      conditions are violated. RESULTS: Our simulation study shows that the adjusted
      chi2 statistic generally produces good empirical type I errors under the
      assumption of a common intracluster correlation coefficient. Even if the
      intracluster correlations are different, the adjusted statistic performs well
      when the groups have equal numbers of clusters (subjects). CONCLUSION: The
      discussion is illustrated using an observational study of caries on the roots of
      teeth.

PMID- 11846854
TI  - Peripheral calcifying odontogenic cyst.
AB  - BACKGROUND: Calcifying odontogenic cyst (COC) is a rare lesion representing about
      1% of jaw cysts. It may occur in a central (intraosseous) or peripheral
      (extraosseous) location. METHOD: A case of peripheral COC located on the gingiva,
      appearing as a painless, circumscribed, pink nodule has been reported. RESULTS:
      Peripheral, in contrast to central, COC tends to affect older patients.
      Peripheral COC is a less aggressive lesion than the central counterpart, and a
      simple excision biopsy is curative. CONCLUSION: The histological finding of a
      keratinized epithelium rich in ghost cells has helped in making the diagnosis.

PMID- 11846855
TI  - The heart protection study: statins for all those at risk?

PMID- 11846856
TI  - Digoxin-drug interactions: study design and generalizability.

PMID- 11846857
TI  - Absence of a pharmacokinetic interaction between digoxin and levofloxacin.
AB  - BACKGROUND: Levofloxacin, a broad-spectrum fluoroquinolone, may enhance digoxin
      bioavailability by eliminating intestinal flora that metabolize digoxin.
      Moreover, levofloxacin, which is eliminated primarily by glomerular filtration
      and active tubular secretion, may alter the elimination rate of digoxin. Because
      of the narrow therapeutic index of digoxin, it is important to evaluate the
      potential for interaction with levofloxacin when administered concomitantly.
      METHODS: This was a placebo-controlled, randomized, double-blind, two-phase
      crossover study. Twelve healthy subjects (six males and six females) received 500
      mg twice/day oral doses of levofloxacin or placebo for 6 days and a single oral
      dose of 0.4 mg digoxin on the morning of study day 5 along with levofloxacin or
      placebo. RESULTS: There was no significant effect of levofloxacin on the
      pharmacokinetics (Cmax, AUC, and other disposition parameters) of oral digoxin.
      Steady-state levofloxacin absorption and disposition kinetics were also similar
      in the presence or absence of digoxin. CONCLUSIONS: Results of this study suggest
      that an important pharmacokinetic interaction between levofloxacin and digoxin is
      unlikely to occur when administered concomitantly.

PMID- 11846858
TI  - Effects of the concomitant administration of tamsulosin (0.8 mg) on the
      pharmacokinetic and safety profile of intravenous digoxin (Lanoxin) in normal
      healthy subjects: a placebo-controlled evaluation.
AB  - A 20-day, nonrandomized, open-label, placebo-controlled study was performed to
      investigate whether concomitant administration of tamsulosin (0.8 mg) affects the
      pharmacokinetic and safety profile of intravenous digoxin (0.5 mg) in healthy
      subjects. Ten healthy subjects aged 21-39 years received a single oral dose of
      placebo on study days 1-8 and tamsulosin on days 9-18. Tamsulosin was initiated
      at 0.4 mg/day and the dose was increased to 0.8 mg/day from day 11. On days 2 and
      15, subjects received a single intravenous dose of digoxin (0.5 mg). Safety
      monitoring was carried out throughout the study. Following digoxin
      administration, blood was drawn and urine collected over a 96-h period for
      pharmacokinetic determinations. Plasma tamsulosin concentrations were measured at
      regular intervals after dosing on day 15. The digoxin pharmacokinetic parameters
      with and without concomitant tamsulosin were compared. No significant difference
      was observed, and no irregularity was found in the plasma tamsulosin
      concentration data. Six subjects experienced adverse events while receiving
      placebo and seven while on tamsulosin. The most frequent adverse event was mild
      dizziness reported by four subjects. Moderate chest pain was reported in two
      subjects, but this was not considered to be related to the administration of the
      study medications. Some significant changes in vital signs were observed;
      however, none was accompanied by symptoms of medical concern. These changes were
      not temporally related to the administration of study drugs. Thus, concurrent
      administration of digoxin with tamsulosin did not produce any change in the
      pharmacokinetics of digoxin and the safety profile was acceptable. As reflected
      in the prescribing information for tamsulosin, no adjustment in tamsulosin dosing
      is required when it is administered concomitantly with digoxin.

PMID- 11846859
TI  - Assessment of new onset postcoronary artery bypass surgery atrial fibrillation:
      current practice pattern review and the development of treatment guidelines.
AB  - BACKGROUND: The incidence of postcoronary artery bypass graft (CABG) atrial
      fibrillation (AF) is 22.5% at the QEII Health Sciences Centre and the mean length
      of stay is 5.5 days greater than for those patients who do not experience this
      complication. Appropriate pharmacological management is important to prevent the
      potential morbidity from AF, such as thromboembolism, congestive heart failure,
      cardiogenic shock and coronary ischemia. This project compared current practice
      patterns in the management of post-CABG AF with local practice pattern beliefs
      and evidence from the primary literature. Subsequently, treatment guidelines were
      designed to help guide a rationale treatment approach. OBJECTIVE: To promote
      appropriate treatment strategies for post-CABG AF and increase local practitioner
      awareness of drug-use outcomes by developing consensus treatment guidelines.
      DESIGN: There were three phases. In phase 1, a retrospective chart analysis of 35
      post-CABG AF patients over three consecutive months was conducted to assess
      current practice patterns. All published studies on this subject were also
      collected and analysed. A survey of pharmacological treatment preferences was
      distributed to local stakeholders during phase 2. The third phase involved the
      development and implementation of treatment guidelines. RESULTS: This study
      identified a highly variable approach to the treatment of post-CABG AF. The mean
      number of agents used to treat AF post-CABG was two (range 1-4); all patients
      (100%) were prescribed rate-controlling agents and 37% were prescribed an
      antiarrhythmic drug. There was also a mismatch between practice pattern beliefs
      and actual practice. CONCLUSIONS: This reinforced the need for a consistent
      treatment approach that was facilitated with the development and implementation
      of local guidelines.

PMID- 11846860
TI  - Compatibility of ropivacaine with morphine, sufentanil, fentanyl, or clonidine.
AB  - BACKGROUND: Ropivacaine hydrochloride (HCl) ('Naropin') is a long-acting local
      anaesthetic agent, administered epidurally to patients undergoing various
      surgical procedures. A combination of local anaesthetic and opioid is often
      administered for the management of severe pain to ensure that a minimal dose of
      each is used. Ropivacaine might be used in combination with an alpha2-adrenergic
      agonist for the management of visceral pain. Stability data have shown that
      ropivacaine is compatible with the systemic narcotic opioid analgesics morphine
      sulphate, sufentanil citrate and fentanyl citrate for 14 days in a Polybag
      (AstraZeneca-AB, Sweden), but no data have been obtained for the longer-term
      compatibility of ropivacaine with these opioids or with the alpha2-adrenergic
      agonist clonidine HCl. OBJECTIVE: This study used the Mark II Polybag
      (AstraZeneca-AB, Sweden) to test the physical and chemical compatibility of these
      products for up to 30 days. METHODS: Ropivacaine HCl solution for epidural
      infusion, 2 mg/mL, in 200 mL Mark II Polybag and commercially available additives
      in glass ampoules or vials were used as starting material. Appropriate admixtures
      were made and their appearance, pH, and drug concentrations were monitored on
      days 0, 7, 14, and 30. The appearance of the admixtures was examined with the aid
      of a stereomicroscope (Olympus, no. 220186, New York, USA) at 10x magnification.
      Drug concentration and enantiomeric purity were determined using high-performance
      liquid chromatographic analysis. RESULTS: All combinations at all doses stayed
      within the compatibility criteria (if no visible signs of physical changes in the
      admixture appeared throughout the 30 days of storage, and if pH and drug
      concentrations in each admixture did not vary by more than 10% between day 0 and
      days 7, 14, or 30 in storage). In addition, there were no important differences
      in the enantiomeric purity of ropivacaine with each combination. CONCLUSION: The
      study demonstrated that ropivacaine was suitable for use in combination with the
      opioids morphine sulphate, sufentanil citrate, and fentanyl citrate, or with the
      alpha2-adrenergic agonist clonidine HCl, for up to 30 days of storage before the
      management of severe or visceral pain. From a microbiological point of view,
      combinations not prepared under aseptic conditions should be used immediately.
      'Naropin' is a trade mark of the AstraZeneca group of companies.

PMID- 11846861
TI  - Identifying patient and physician characteristics that affect compliance with
      antihypertensive medications.
AB  - BACKGROUND: Compliance with antihypertensive medications is essential to the
      clinical management of hypertension. Poor compliance with antihypertensive
      medications has often been associated with treatment failure and disease
      progression. OBJECTIVE: To identify patient and prescriber characteristics that
      may influence compliance with antihypertensive medications. METHOD: We used
      pharmacy records within the Veterans Health Administration, a database which
      included 1292 patients and 656 physicians over a 2-year time period from April 1,
      1996, to April 1, 1998. The level of compliance with antihypertensive medications
      was assessed using a measure developed for this purpose within the
      Administration. Three separate ordinary least squares regression models were
      conducted to ascertain the effects of patient and physician characteristics on
      compliance. RESULTS: Despite the importance of compliance in the clinical
      management of hypertension, poor compliance with antihypertensive drug treatment
      was still widespread. Patients who were younger and less active in their
      treatment decisions tended to be less compliant (P < 0.05 and 0.05,
      respectively). Health care providers who were older, residents in speciality
      care, and physicians (as compared with non-physicians) had patients who were also
      less likely to be compliant (P < 0.01, 0.01, and 0.05, respectively). CONCLUSION:
      These findings suggest that in order to increase the effectiveness of medical
      care for hypertension, it is important to improve compliance with
      antihypertensive agents.

PMID- 11846862
TI  - Determinants of physicians' attitude towards prescribing.
AB  - OBJECTIVE: To identify the primary care physicians' (PCP) characteristics that
      are associated with their prescribing attitude. METHODS: A validated
      questionnaire was sent to randomly selected PCPs stratified in three groups
      according to any higher qualification in family medicine. RESULT: The best
      predictor for orientation of quality of care in prescribing was the country of
      qualification. Duration after qualification was negatively associated with PCP's
      belief in the use of drugs. Physicians who were female, with higher
      qualification, sooner after qualification, and working in group practice were
      less likely to perceive pressure from patients to prescribe, with group practice
      being the most significant determinant. CONCLUSION: Different physician factors
      affect different aspects of PCPs' prescribing attitude. As duration after
      qualification was an important but negative attribute, quality use of medication
      should be emphasized in continuing medical education.

PMID- 11846863
TI  - Using case-control studies for prescribing research.
AB  - In this review, the principles of design, analysis and interpretation of case
      control studies are illustrated by considering the evidence from case-control
      studies that link hormone replacement therapy to venous thromboembolism.

PMID- 11846865
TI  - Evidence-based pediatric allergy practice.

PMID- 11846864
TI  - Gynecomastia with sulpiride.
AB  - OBJECTIVE: Neuroleptic agents have been associated with gynecomastia, but
      evidence for a causal link is insufficient. We describe a case of unilateral
      gynecomastia without galactorrhea in a 38-year-old man during sulpiride treatment
      for generalized anxiety disorder. The patient had been treated with sulpiride
      (100 mg/day) for about 5 months by a primary care physician. In this patient, no
      specific endocrine alterations were found, except for a marked increase in
      prolactin (PRL) level and slight decrease in testosterone (T)/estradiol (E2)
      ratio. Drug withdrawal led to a reduction of the lump. Sulpiride is a substituted
      benzamide with selective dopaminergic blocking activity. From the marked increase
      in PRL level and the slight decrease in T/E2 ratio observed during sulpiride
      therapy, it is proposed that sulpiride may induce gynecomastia by inhibiting
      hypothalamic-pituitary function directly, and/or indirectly through hyperPRLemia.

PMID- 11846867
TI  - Do early childhood immunizations influence the development of atopy and do they
      cause allergic reactions?
AB  - Concerns about allergic side-effects of vaccines and about a possible promotion
      of allergic diseases contribute to incomplete vaccination rates in childhood.
      This article reviews the current understanding of these issues. There is evidence
      that pertussis and diphtheria/tetanus antigens elicit immunoglobulin E (IgE)
      antibody formation as part of the immune response. In murine models, pertussis
      toxin is an effective adjuvant for IgE formation against simultaneously
      administered antigens. In children, however, sensitization to unrelated antigens
      or development of allergic diseases do not seem to be augmented. In contrast,
      bacille Calmette-Guerin (BCG) and measles vaccination have been proposed as
      suppressors of allergy because of their T helper 1 (Th1)-fostering properties. In
      the murine system, BCG inhibits allergic sensitization and airway hyper
      reactivity. Some epidemiological studies in humans suggest an inhibitory effect
      of tuberculosis on allergy. BCG vaccination in children, however, has no or
      merely a marginal suppressive effect on atopy. Other vaccine components such as
      egg proteins, gelatin, and antibiotics are a potential hazard to children with
      severe clinical reactions to these allergens. These rare children should be
      vaccinated under special precautions. In conclusion, vaccination programs do not
      explain the increasing prevalence of allergic diseases, but individual children
      may uncommonly develop an allergic reaction to a vaccine. The risks of not
      vaccinating children, however, far outweigh the risk for allergy. Therefore,
      childhood vaccination remains an essential part of child health programs and
      should not be withheld, even from children predisposed for allergy.

PMID- 11846868
TI  - High levels of urinary eosinophil protein X in young asthmatic children predict
      persistent atopic asthma.
AB  - Levels of urinary eosinophil protein X (U-EPX) and eosinophil counts were
      measured in 32 children (12-36 months of age) who were hospitalized for acute
      asthma, and the U-EPX levels were measured in 20 healthy children of the same
      age. The ability of these parameters to predict persistent asthma (at least one
      wheezing episode during the last 6 months) and atopic asthma (a positive skin
      prick test [SPT]), was evaluated at a follow-up 2 years later. On admission,
      levels of U-EPX were higher in children with asthma (median: 120 microg/mmol of
      creatinine; quartiles: 67-123 microg/mmol of creatinine) than in controls (60
      microg/mmol of creatinine, 38-74 microg/mmol of creatinine; p< 0.001). The U-EPX
      level was higher in those with persistent atopic asthma at follow-up (173
      microg/mmol of creatinine, 123-196 microg/mmol of creatinine, n = 16), than in
      those with persistent non-atopic asthma (73 microg/mmol creatinine, 46-105
      microg/mmol of creatinine, n = 8; p< 0.05), and higher than in those with
      transient asthma (no symptoms at follow-up) (106 microg/mmol creatinine; 42-167
      microg/mmol of creatinine, n = 8; p< 0.05). By multiple logistic regression
      analysis, U-EPX was the only parameter able to predict persistent atopic asthma;
      eosinophil counts, parental atopy, age or gender could not. Parental atopy was
      the only parameter predictive for persistent asthma, regardless of atopic status.
      In conclusion, levels of U-EPX, but not eosinophil counts, measured in young
      children hospitalized with acute asthma can predict the persistence of atopic
      asthma 2 years later.

PMID- 11846869
TI  - Analysis of sputum taken from wheezy and asthmatic infants and children, with
      special reference to respiratory infections.
AB  - Children who are destined to develop asthma are considered to be susceptible to a
      variety of respiratory pathogens. To elucidate respiratory inflammation among
      these children, we measured the levels of eosinophil cationic protein (ECP) and
      tryptase in sputum taken from three different groups of wheezy infants and young
      children: those with a first wheeze (n = 15); those with recurrent wheeze (n =
      27); and those with recurrent wheeze with respiratory distress, namely asthma (n
      = 56). The numbers of eosinophils or metachromatic cells determined by
      microscopic analysis of sputum samples were also evaluated in combination with
      the ECP and tryptase levels. Although neither sputum ECP nor tryptase was a clear
      discriminative marker that differentiated the three different types of wheezy
      disease, ECP levels in sputum from the asthma group were significantly higher
      (2,269.2 +/- 6,216.8 ng/g) than those in the recurrent wheezy group (440.3 +/-
      1,199.8 ng/g) or in the first-wheeze group (209.0 +/- 172.9 ng/g). A similar
      trend was observed with tryptase levels in sputum, but there were no significant
      differences among the three groups. Sputum taken from asthmatic children showed a
      marked accumulation of eosinophils. However, an accumulation of eosinophils in
      sputum (even in the presence of an elevated level of sputum ECP) was not
      identified in the asthmatic infants < 1 year of age. An accumlation of
      eosinophils in sputum was not evident until children became > 1 year old and
      thereafter the eosinophils rapidly increased in number until the children reached
      5 years of age. It was noteworthy that sputa positive for pathogenic bacteria,
      taken from the 1- and 2-year-old asthmatic infants, had a tendency to show high
      levels of ECP but a reduced number of eosinophils. Along with the wheezy episodes
      induced by viral infection, primarily and occasionally in combination with
      secondary bacterial infection, eosinophil activation and infiltration may
      develop. These predestined immune reactions to various pathogens might be
      associated with triggering the onset of asthma.

PMID- 11846870
TI  - Childhood asthma admissions: determinants of short stay.
AB  - The objective of this study was to identify the determinants of short hospital
      stay (< 24 h) among children admitted because of an acute asthma exacerbation.
      Computerized health records were used to identify children with a discharge
      diagnosis of asthma (ICD code 493.0) at the Hospital for Sick Children, Toronto,
      during the period October 1994 to October 1995. Cases were children with a length
      of hospital stay of < 24 h (short-stay group) and controls were children with a
      length of stay of > 24 h (long-stay group). Clinical and demographic data were
      extracted from the medical record. Over the 12-month period, 485 children were
      hospitalized because of asthma. Of these, 121 (25%) had short-stay admissions (<
      24 h), whereas 364 (75%) had long-stay admissions (> 24 h). Simple random
      sampling was used to select 85 children from each of the two groups. There were
      no differences between the two groups regarding language, primary care physician,
      asthma history, management prior to emergency department (ED) presentation,
      respiratory rate on presentation, use of the observation unit, and time in the
      ED. Logistic regression analyses identified three variables associated with short
      hospital stay: milder asthma (adjusted odds ratio [OR] 4.9), male gender
      (adjusted OR 2.4), and availability of a delivery device at home (adjusted OR
      2.0). In conclusion, many children admitted to hospital because of an asthma
      exacerbation have short, yet expensive, hospital stays. The results of this study
      highlight the importance of developing alternative models of health care delivery
      for asthmatic children requiring short hospital contact.

PMID- 11846871
TI  - Reasons for and costs of hospitalization for pediatric asthma: a prospective 1
      year follow-up in a population-based setting.
AB  - The aims of this study were to examine the frequency of, and the reasons for,
      emergency hospitalization for asthma among children. In addition, the costs of
      hospital treatment, preventive medication, and productivity losses of the
      caregivers were evaluated in a population-based setting during 1 year. Data on
      purchases of regular asthma medication were obtained from the Social Insurance
      Institution. In total, 106 (2.3/1000) children aged up to 15 years were admitted
      136 times for asthma exacerbation to the Kuopio University Hospital in 1998. This
      represented approximately 5% of all children with asthma in the area. The trigger
      for the exacerbation was respiratory infection in 63% of the episodes, allergen
      exposure in 24%, and unknown in 13%. The age-adjusted risk for admittance was
      5.3% in children on inhaled steroids, 5.8% in those on cromones, and 7.9% in
      those with no regular medication for asthma. The mean direct cost for an
      admission was $1,209 (median $908; range $454-6,812) and the indirect cost was
      $358 ($316; $253-1,139). The cost of regular medication for asthma was, on
      average, $272 per admitted child on maintenance. The annual total cost as a
      result of asthma rose eight-fold if a child on regular medication was admitted
      for asthma.

PMID- 11846872
TI  - Cow's milk protein intolerance and chronic constipation in children.
AB  - Cow's milk protein (CMP) allergy was investigated in 25 children (age-range 3
      months to 11 years) with chronic constipation. A diagnosis of constipation was
      made on the basis of a history of painful elimination of hard stools for at least
      1 month, whether or not associated with a reduced frequency of stools or soiling.
      The children were evaluated using clinical parameters and the following
      laboratory tests: total serum immunoglobulin E (IgE); specific IgE
      (radioallergosorbent test [RAST]) for whole cow's milk, alpha-lactoalbumin, beta
      lactoglobulin, and a food group; and skin-prick tests with whole milk, alpha
      lactoalbumin, beta-lactoglobulin, and casein. Following the evaluation, the
      children were submitted to a CMP-free diet for a period of 4 weeks. In seven
      patients (28%), constipation disappeared during the CMP-free diet and reappeared
      within 48-72 h following challenge with cow's milk. In two infants a rectal
      biopsy revealed allergic colitis and they therefore did not undergo the
      challenge. High serum levels of total IgE were observed in five of the children
      who showed a clinical improvement (71%), a positive skin-test in two (29%), and
      detectable specific IgE in two (29%). These results suggest that CMP allergy or
      intolerance should be considered as a cause of chronic refractory constipation in
      children, although the underlying mechanism still require further investigation.

PMID- 11846873
TI  - Local and systemic wound-induction of RNase and nuclease activities in
      Arabidopsis: RNS1 as a marker for a JA-independent systemic signaling pathway.
AB  - Induction of defense-related genes is one way in which plants respond to
      mechanical injury. We investigated whether RNases are involved in the wound
      response in Arabidopsis thaliana. As in other plant systems, several activities
      are induced with various timings in damaged leaves, stems and seedlings in
      Arabidopsis, including at least three bifunctional nucleases, capable of
      degrading both RNA and DNA, as well as RNS1, a member of the ubiquitous RNase
      T(2) family of RNases. The strong induction of RNS1 is particularly interesting
      because it occurs both locally and systemically following wounding. The systemic
      induction of this RNase indicates that members of this family may be involved in
      defense mechanisms in addition to their previously hypothesized functions in
      nutrient recycling and remobilization. Additionally, the systemic induction
      appears to be controlled independently of jasmonic acid, and the local induction
      of RNS1 and the nuclease activities are independent of both JA and
      oligosaccharide elicitors. Consequently, a novel systemic pathway, likely
      involving a third signal, appears to exist in Arabidopsis.

PMID- 11846874
TI  - Condensin and cohesin knockouts in Arabidopsis exhibit a titan seed phenotype.
AB  - The titan (ttn) mutants of Arabidopsis exhibit striking alterations in chromosome
      dynamics and cell division during seed development. Endosperm defects include
      aberrant mitoses and giant polyploid nuclei. Mutant embryos differ in cell size,
      morphology and viability, depending on the locus involved. Here we demonstrate
      that three TTN genes encode chromosome scaffold proteins of the condensin (SMC2)
      and cohesin (SMC1 and SMC3) classes. These proteins have been studied extensively
      in yeast and animal systems, where they modulate chromosome condensation,
      chromatid separation, and dosage compensation. Arabidopsis contains single copies
      of SMC1 and SMC3 cohesins. We used forward genetics to identify duplicate T-DNA
      insertions in each gene. These mutants (ttn7 and ttn8) have similar titan
      phenotypes: giant endosperm nuclei and arrested embryos with a few small cells. A
      single SMC2 knockout (ttn3) was identified and confirmed by molecular
      complementation. The weak embryo phenotype observed in this mutant may result
      from expression of a related gene (AtSMC2) with overlapping functions. Further
      analysis of titan mutants and the SMC gene family in Arabidopsis should provide
      clues to chromosome mechanics in plants and insights into the regulation of
      nuclear activity during endosperm development.

PMID- 11846875
TI  - Important roles of drought- and cold-inducible genes for galactinol synthase in
      stress tolerance in Arabidopsis thaliana.
AB  - Raffinose family oligosaccharides (RFO) accumulating during seed development are
      thought to play a role in the desiccation tolerance of seeds. However, the
      functions of RFO in desiccation tolerance have not been elucidated. Here we
      examine the functions of RFO in Arabidopsis thaliana plants under drought- and
      cold-stress conditions, based on the analyses of function and expression of genes
      involved in RFO biosynthesis. Sugar analysis showed that drought-, high salinity-
      and cold-treated Arabidopsis plants accumulate a large amount of raffinose and
      galactinol, but not stachyose. Raffinose and galactinol were not detected in
      unstressed plants. This suggests that raffinose and galactinol are involved in
      tolerance to drought, high salinity and cold stresses. Galactinol synthase (GolS)
      catalyses the first step in the biosynthesis of RFO from UDP-galactose. We
      identified three stress-responsive GolS genes (AtGolS1, 2 and 3) among seven
      Arabidopsis GolS genes. AtGolS1 and 2 were induced by drought and high-salinity
      stresses, but not by cold stress. By contrast, AtGolS3 was induced by cold stress
      but not by drought or salt stress. All the GST fusion proteins of GST-AtGolS1, 2
      and 3 expressed in Escherichia coli had galactinol synthase activities.
      Overexpression of AtGolS2 in transgenic Arabidopsis caused an increase in
      endogenous galactinol and raffinose, and showed reduced transpiration from leaves
      to improve drought tolerance. These results show that stress-inducible galactinol
      synthase plays a key role in the accumulation of galactinol and raffinose under
      abiotic stress conditions, and that galactinol and raffinose may function as
      osmoprotectants in drought-stress tolerance of plants.

PMID- 11846876
TI  - Identification of a novel gene HYS1/CPR5 that has a repressive role in the
      induction of leaf senescence and pathogen-defence responses in Arabidopsis
      thaliana.
AB  - We isolated two allelic mutants of Arabidopsis thaliana that showed an early
      senescence phenotype under light/dark and continuous dark photo regimes, and
      designated the mutant hypersenescence1 (hys1). The hys1 mutants decreased
      chlorophyll and protein content, lowered the efficiency of photosystem II, and
      accumulated several senescence upregulated gene transcripts earlier than the wild
      type plants. In addition to these senescence features, the hys1 seedlings
      responded more intensely to exogenously applied sugars than did wild-type
      seedlings in sugar-induced growth inhibition and sugar-mediated transcript
      accumulation, both of which are known to be regulated by the sugar sensor
      hexokinase. The hys1 mutant also had abnormal trichomes. Map-based cloning of the
      HYS1 gene identified a novel gene that encodes a protein with a potential nuclear
      localization signal in the amino-terminal region, and five putative transmembrane
      domains in the carboxyl-terminal region. Furthermore, we found that the
      constitutive expressor of pathogenesis-related genes 5 (cpr5) mutant, which shows
      spontaneous pathogen-defence responses and abnormal trichomes, has a point
      mutation in the HYS1 gene, suggesting that these independently isolated mutants
      are allelic to each other. Although no definite conclusion can be drawn from
      these results, we suggest that altered sensitivity to sugars and/or enhanced
      efficiency of sugar signalling in the hys1/cpr5 mutant may have important roles
      in the initiation processes of leaf senescence and pathogen-defence responses in
      Arabidopsis.

PMID- 11846877
TI  - Arabidopsis RPP4 is a member of the RPP5 multigene family of TIR-NB-LRR genes and
      confers downy mildew resistance through multiple signalling components.
AB  - In Arabidopsis, RPP4 confers resistance to Peronospora parasitica (P.p.) races
      Emoy2 and Emwa1 (downy mildew). We identified RPP4 in Col-0 as a member of the
      clustered RPP5 multigene family encoding nucleotide-binding leucine-rich repeat
      proteins with Toll/interleukin-1 receptor domains. RPP4 is the orthologue of RPP5
      which, in addition to recognizing P.p. race Noco2, also mediates resistance to
      Emoy2 and Emwa1. Most differences between RPP4 and RPP5 occur in residues that
      constitute the TIR domain and in LRR residues that are predicted to confer
      recognition specificity. RPP4 requires the action of at least 12 defence
      components, including DTH9, EDS1, PAD4, PAL, PBS2, PBS3, SID1, SID2 and salicylic
      acid. The ndr1, npr1 and rps5-1 mutations partially compromise RPP4 function in
      cotyledons but not in true leaves. The identification of RPP4 as a TIR-NB-LRR
      protein, coupled with its dependence on certain signalling components in true
      leaves, is consistent with the hypothesis that distinct NB-LRR protein classes
      differentially signal through EDS1 and NDR1. Our results suggest that RPP4
      mediated resistance is developmentally regulated and that in cotyledons there is
      cross-talk between EDS1 and NDR1 signalling and processes regulating systemic
      acquired resistance.

PMID- 11846878
TI  - The GAMYB protein from barley interacts with the DOF transcription factor BPBF
      and activates endosperm-specific genes during seed development.
AB  - HvGAMYB, a MYB transcription factor previously shown to be expressed in barley
      aleurone cells in response to gibberellin during germination, also has an
      important role in gene regulation during endosperm development. The mRNA was
      detected early (10 DAF) in the seeds where it accumulates, not only in the
      aleurone layer, starchy endosperm, nucellar projection and vascular tissue, but
      also in the immature embryo as shown by in situ hybridization analysis. The
      HvGAMYB protein, expressed in bacteria, binds to oligonucleotides containing the
      5'-TAACAAC-3' or 5'-CAACTAAC-3' sequences, derived from the promoter regions of
      the endosperm-specific genes Hor2 and Itr1, encoding a B-hordein and trypsin
      inhibitor BTI-CMe, respectively. Binding is prevented when these motifs are
      mutated to 5'-TgACAAg-3' and 5'-CgACTgAC-3'. Transient expression experiments in
      co-bombarded developing endosperms demonstrate that HvGAMYB trans-activates
      transcription from native Hor2 and Itr1 promoters through binding to the intact
      motifs described above. Trans-activation of the Hor2 promoter also requires an
      intact prolamine box (PB). This suggests that HvGAMYB interacts in developing
      barley endosperms with the PB-binding factor BPBF, an endosperm-specific DOF
      transcriptional activator of the Hor2 gene. The in vivo interaction experiment
      between HvGAMYB and BPBF was done in the yeast two-hybrid system, where HvGAMYB
      potentiates the BPBF trans-activation capacity through interaction with its C
      terminal domain.

PMID- 11846879
TI  - Two distinct high-affinity sulfate transporters with different inducibilities
      mediate uptake of sulfate in Arabidopsis roots.
AB  - Sulfate transporters present at the root surface facilitate uptake of sulfate
      from the environment. Here we report that uptake of sulfate at the outermost cell
      layers of Arabidopsis root is associated with the functions of highly and low
      inducible sulfate transporters, Sultr1;1 and Sultr1;2, respectively. We have
      previously reported that Sultr1;1 is a high-affinity sulfate transporter
      expressed in root hairs, epidermal and cortical cells of Arabidopsis roots, and
      its expression is strongly upregulated in plants deprived of external sulfate. A
      novel sulfate transporter gene, Sultr1;2, identified on the BAC clone F28K19 of
      Arabidopsis, encoded a polypeptide of 653 amino acids that is 72.6% identical to
      Sultr1;1 and was able to restore sulfate uptake capacity of a yeast mutant
      lacking sulfate transporter genes (K(m) for sulfate = 6.9 +/- 1.0 microm).
      Transgenic Arabidopsis plants expressing the fusion gene construct of the
      Sultr1;2 promoter and green fluorescent protein (GFP) showed specific
      localization of GFP in the root hairs, epidermal and cortical cells of roots, and
      in the guard cells of leaves, suggesting that Sultr1;2 may co-localize with
      Sultr1;1 in the same cell layers at the root surface. Sultr1;1 mRNA was
      abundantly expressed under low-sulfur conditions (50-100 microm sulfate), whereas
      Sultr1;2 mRNA accumulated constitutively at high levels under a wide range of
      sulfur conditions (50-1500 microm sulfate), indicating that Sultr1;2 is less
      responsive to changes in sulfur conditions. Addition of selenate to the medium
      increased the level of Sultr1;1 mRNA in parallel with a decrease in the internal
      sulfate pool in roots. The level of Sultr1;2 mRNA was not influenced under these
      conditions. Antisense plants of Sultr1;1 showed reduced accumulation of sulfate
      in roots, particularly in plants treated with selenate, suggesting that the
      inducible transporter Sultr1;1 contributes to the uptake of sulfate under
      stressed conditions.

PMID- 11846880
TI  - Selenate-resistant mutants of Arabidopsis thaliana identify Sultr1;2, a sulfate
      transporter required for efficient transport of sulfate into roots.
AB  - To investigate how plants acquire and assimilate sulfur from their environment,
      we isolated and characterized two mutants of Arabidopsis thaliana deficient in
      sulfate transport. The mutants are resistant to selenate, a toxic analogue of
      sulfate. They are allelic to each other and to the previously isolated sel1
      (selenate-resistant) mutants, and have been designated sel1-8 and sel1-9. Root
      elongation in these mutants is less sensitive to selenate than in wild-type
      plants. Sulfate uptake into the roots is impaired in the mutants under both
      sulfur-sufficient and sulfur-deficient conditions, but transport of sulfate to
      the shoot is not affected. The sel1 mutants contain lesions in the sulfate
      transporter gene Sultr1;2 located on the lower arm of chromosome 1. The sel1-1,
      sel1-3 and sel1-8 mutants contain point mutations in the coding sequences of
      Sultr1;2, while the sel1-9 mutant has a T-DNA insertion in the Sultr1;2 promoter.
      The Sultr1;2 cDNA derived from wild-type plants is able to complement
      Saccharomyces cerevisiae mutants defective in sulfate transport, but the Sultr1;2
      cDNA from sel1-8 is not. The Sultr1;2 gene is expressed mainly in roots, and
      accumulation of transcripts increases during sulfate deprivation. Examination of
      transgenic plants containing the Sultr1;2 promoter fused to the GUS-reporter gene
      indicates that Sultr1;2 is expressed mainly in the root cortex, the root tip and
      lateral roots. Weaker expression of the reporter gene was observed in hydathodes,
      guard cells and auxiliary buds of leaves, and in anthers and the basal parts of
      flowers. The results indicate that Sultr1;2 is primarily involved in importing
      sulfate from the environment into the root.

PMID- 11846881
TI  - Prior exposure to lipopolysaccharide potentiates expression of plant defenses in
      response to bacteria.
AB  - Lipopolysaccharide (LPS) is a ubiquitous component of Gram-negative bacteria
      which has a number of diverse biological effects on eukaryotic cells. In contrast
      to the large body of work in mammalian and insect cells, the effects of LPS on
      plant cells have received little attention. LPS can induce defense-related
      responses in plants, but in many cases these direct effects are weak. Here we
      have examined the effects of prior inoculation of LPS on the induction of plant
      defense-related responses by phytopathogenic xanthomonads in leaves of pepper
      (Capsicum annuum). The resistance of pepper to incompatible strains of
      Xanthomonas axonopodis pv. vesicatoria or to X. campestris pv. campestris is
      associated with increased synthesis of the hydroxycinnamoyl-tyramine conjugates,
      feruloyl-tyramine (FT) and coumaroyl-tyramine (CT). FT and CT are produced only
      in trace amounts in response to compatible strains of X. axonopodis pv.
      vesicatoria. Treatment of leaves with LPS from a number of bacteria did not
      induce the synthesis of FT and CT but altered the kinetics of induction upon
      subsequent bacterial inoculation. In incompatible interactions FT and CT
      synthesis was accelerated, whereas in compatible interactions synthesis was also
      considerably enhanced. The ability of the tissue to respond more rapidly was
      induced within 4 h of LPS treatment and the potentiated state was maintained for
      at least 38 h. Earlier treatment with LPS also potentiated the expression of
      other defense responses such as transcription of genes encoding acidic beta-1,3
      glucanase. Our findings indicate a wider role for LPS in plant-bacterial
      interactions beyond its limited activity as a direct inducer of plant defenses.

PMID- 11846882
TI  - Position dependent expression of GL2-type homeobox gene, Roc1: significance for
      protoderm differentiation and radial pattern formation in early rice
      embryogenesis.
AB  - In early plant embryogenesis, the determination of cell fate in the protodermal
      cell layer is considered to be the earliest event in radial pattern formation. To
      elucidate the mechanisms of epidermal cell fate determination and radial pattern
      formation in early rice embryogenesis, we have isolated a GL2-type homeobox gene
      Roc1 (Rice outermost cell-specific gene1), which is specifically expressed in the
      protoderm (epidermis). In early rice embryogenesis, cell division occurs randomly
      and the morphologically distinct layer structure of the protoderm cannot be
      observed until the embryo reaches more than 100 microm in length. Nonetheless, in
      situ hybridization analyses revealed that specific expression of Roc1 in the
      outermost cells is established shortly after fertilization, much earlier than
      protoderm differentiation. In the regeneration process from callus, the Roc1 gene
      is also expressed in the outermost cells of callus in advance of tissue and organ
      differentiation, and occurs independently of whether the cells will differentiate
      into epidermis in the future or not. Furthermore, this cell-specific Roc1
      expression could be induced flexibly in the newly produced outermost cells when
      we cut the callus. These findings suggest that the expression of Roc1 in the
      outermost cells may be dependent on the positional information of cells in the
      embryo or callus prior to the cell fate determination of the protoderm
      (epidermis). Furthermore, the Roc1 expression is downregulated in the inner cells
      of ligule, which have previously been determined as protodermal cells, also
      suggesting that the Roc1 expression is position dependent and that this position
      dependent Roc1 expression is important also in post-embryonic protoderm
      (epidermis) differentiation.

PMID- 11846883
TI  - Relationship between small antisense RNAs and aberrant RNAs associated with sense
      transgene mediated gene silencing in tomato.
AB  - We investigated the occurrence and properties of small sense and antisense RNAs
      and aberrant transcripts in transgenic tomato plants exhibiting post
      transcriptional silencing of the endogenous polygalacturonase (PG) sense gene and
      a truncated homologous transgene. Small antisense RNAs, about 23 nucleotides in
      size, were present in the leaves and immature green fruit where the transgene was
      transcribed in the absence of transcripts from the fruit ripening-specific
      endogenous PG gene. This suggests that the small antisense RNAs were produced
      from the transgene, which was supported by their failure to hybridise with the 3'
      half of the endogenous PG gene, the region that was excluded from the transgene.
      The features of two aberrant RNAs, corresponding to the 5' and 3' halves of the
      endogenous gene, strongly suggest that they arise by endonucleolytic cleavage of
      endogenous PG mRNA. The region where cleavage occurs is associated with the
      preferential production of small RNAs from the 3' end of the transgene. These
      results suggest a model where small antisense RNAs generated from the 3' end of
      the transgene anneal to the endogenous mRNA, resulting in cleavage at or near the
      annealing regions.

PMID- 11846884
TI  - Spatial analysis of plant metabolism: sucrose imaging within Vicia faba
      cotyledons reveals specific developmental patterns.
AB  - During legume embryogenesis the differentiation of the cotyledons proceeds
      gradually in a wave-like manner. The process is metabolically and genetically
      controlled and regulated by sugars. In order to perform a spatial and temporal
      analysis of the sugar distribution pattern a new method was developed to
      specifically measure sucrose directly in tissues via bioluminescence and single
      photon counting. This enabled a quantitative sucrose imaging with a resolution
      close to the single cell level. The procedure was applied on sections of Vicia
      faba cotyledons covering the main stages of histodifferentiation. Young embryos
      before the storage phase contained moderate levels of sucrose, which were evenly
      distributed. At the onset of maturation high concentrations were present within a
      tissue layer covering the outward half of the coytledons. This layer was directly
      underneath the epidermis expressing a sucrose transporter gene indicating that
      epidermal transporters caused the high sucrose accumulation in the underlying
      tissue. At that stage the sucrose gradient was inversely oriented compared with
      cell size and the starch content. Cells within the interior were larger,
      contained starch but low sucrose. Thus, the sucrose pattern is controlled by
      uptake activity and permeability within the parenchyma. However, during the main
      storage phase actively elongating and starch accumulating cells contain highest
      sucrose concentrations indicating that differences in growth and starch
      accumulation also affect intracotyledonary sugar distribution. High sucrose
      concentrations were correlated with transcript levels of sucrose synthase and ADP
      Glc pyrophosphorylase indicating a signaling function for sucrose to induce
      starch biosynthesis on the gene expression level. Carbon flux through the sucrose
      synthase pathway towards starch increased when hexoses levels decreased.

PMID- 11846886
TI  - Partial identification by site-directed mutagenesis of a cell growth inhibitory
      site on the human galectin-1 molecule.
AB  - BACKGROUND: Previous work, by us and others, has shown that mammalian galectins-1
      have a growth-inhibitory activity for mammalian cells which is apparently
      independent of their beta-galactoside binding site. RESULTS: We have made
      recombinant human galectin-1 as a bacterial fusion protein with an N-terminal
      hexahistidine tag. This protein displays both haemagglutination and growth
      inhibitory activities, even in the presence of the hexahistidine tag. Site
      directed mutagenesis of this protein has confirmed the independent nature of the
      protein sites responsible for the two biological activities. Mutant proteins were
      created, which displayed each activity in the absence of the other. CONCLUSIONS:
      Human galectin-1 possesses a growth-inhibitory site, which is not part of the
      beta-galactoside binding site. A surface loop, comprising amino acid residues 25
      30, and joining two internal beta-strands, forms part of the growth-inhibitory
      site. This region is relatively close to the N-terminus of the protein, and N
      terminal substitutions or extensions also affect growth-inhibitory activity.
      Further experiments will be necessary to fully define this site.

PMID- 11846887
TI  - The mechanisms responsible for 2-dimensional pattern formation in bacterial
      macrofiber populations grown on solid surfaces: fiber joining and the creation of
      exclusion zones.
AB  - BACKGROUND: When Bacillus subtilis is cultured in a complex fluid medium under
      conditions where cell separation is suppressed, populations of multicellular
      macrofibers arise that mature into ball-like structures. The final sedentary
      forms are found distributed in patterns on the floor of the growth chamber
      although individual cells have no flagellar-driven motility. The nature of the
      patterns and their mode of formation are described in this communication.
      RESULTS: Time-lapse video films reveal that fiber-fiber contact in high density
      populations of macrofibers resulted in their joining either by entwining or
      supercoiling. Joining led to the production of aggregate structures that
      eventually contained all of the fibers located in an initial area. Fibers were
      brought into contact by convection currents and motions associated with
      macrofiber self-assembly such as walking, pivoting and supercoiling. Large
      sedentary aggregate structures cleared surrounding areas of other structures by
      dragging them into the aggregate using supercoiling of extended fibers to power
      dragging. The spatial distribution of aggregate structures in 6 mature patterns
      containing a total of 637 structures was compared to that expected in random
      theoretical populations of the same size distributed in the same surface area.
      Observed and expected patterns differ significantly. The distances separating all
      nearest neighbors from one another in observed populations were also measured.
      The average distance obtained from 1451 measurements involving 519 structures was
      0.73 cm. These spacings were achieved without the use of flagella or other
      conventional bacterial motility mechanisms. A simple mathematical model based
      upon joining of all structures within an area defined by the minimum observed
      distance between structures in populations explains the observed distributions
      very well. CONCLUSIONS: Bacterial macrofibers are capable of colonizing a solid
      surface by forming large multicellular aggregate structures that are distributed
      in unique two-dimensional patterns. Cell growth geometry governs in an
      hierarchical way the formation of these patterns using forces associated with
      twisting and supercoiling to drive motions and the joining of structures
      together. Joining by entwining, supercoiling or dragging all require cell growth
      in a multicellular form, and all result in tightly fused aggregate structures.

PMID- 11846885
TI  - Latent transforming growth factor beta-binding protein-3 and fibulin-1C interact
      with the extracellular domain of the heparin-binding EGF-like growth factor
      precursor.
AB  - BACKGROUND: The membrane-bound cell-surface precursor and soluble forms of
      heparin-binding epidermal growth factor-like growth factor (HB-EGF) contribute to
      many cellular developmental processes. The widespread occurrence of HB-EGF in
      cell and tissue types has led to observations of its role in such cellular and
      tissue events as tumor formation, cell migration, extracellular matrix formation,
      wound healing, and cell adherence. Several studies have reported the involvement
      of such extracellular matrix proteins as latent transforming growth factor beta
      binding protein, TGF-beta, and fibulin-1 in some of these processes. To determine
      whether HB-EGF interacts with extracellular matrix proteins we used the
      extracellular domain of proHB-EGF in a yeast two-hybrid system to screen a monkey
      kidney cDNA library. cDNA clones containing nucleotide sequences encoding domains
      of two proteins were obtained and their derived amino acid sequences were
      evaluated. RESULTS: From approximately equal to 3 x 10(6) screened monkey cDNA
      clones, cDNA clones were recovered that contained nucleotide sequences encoding
      domains of the monkey latent transforming growth factor-beta binding protein-3
      (MkLTBP-3) and fibulin-1C protein. The amino acid sequence derived from the
      MkLTBP-3 gene shared 98.6% identity with human LTBP-3 and 86.7% identity with
      mouse LTBP-3 amino acid sequences. The amino acid sequence derived from the
      monkey fibulin-1C gene shared 97.2% identity with human fibulin-1C. Yeast two
      hybrid screens indicate that LTBP-3 and fibulin-1C interact with proHB-EGF
      through their calcium-binding EGF-like modules. CONCLUSIONS: The interactions of
      the extracellular domain of proHB-EGF with LTBP-3 and fibulin-1C suggest novel
      functions for HB-EGF between cell and tissue surfaces.

PMID- 11846888
TI  - Differential response to right unilateral ECT in depressed patients: impact of
      comorbidity and severity of illness [ISRCTN39974945].
AB  - BACKGROUND: Recent electroconvulsive therapy (ECT) efficacy studies of right
      unilateral (RUL) ECT may not apply to real life clinics with a wide range of
      patients with major depressive episodes. METHODS: The study included two groups
      of patients. In addition to a homogeneous group of patients with major depression
      according to DSM-IV criteria with severity of the major depressive episode > 16
      scores on 17-item Hamilton Rating Scale for Depression (HDRS) (Group 1, n = 16),
      we included a heterogeneous group of patients with less severe major depressive
      episodes or with a variety of comorbid conditions (Group 2, n = 24). We randomly
      assigned the patients to an RUL ECT treatment dosed at 5 or 2.5 times seizure
      threshold with an intent-to-treat design. The outcomes measured blindly were
      HDRS, number of treatments, and Mini-Mental State Examination (MMSE). The
      patients were considered to have responded to treatment if the improvement in
      HDRS score was at least 60% and they had a total score of less than ten. RESULTS:
      The Group 2 patients responded poorer (8% vs. 63%), and had more often
      simultaneous worsening in their MMSE scores than Group 1 patients. The
      differences in the outcomes between the two different doses of RUL ECT treatment
      were not statistically significant. CONCLUSIONS: ECT effectiveness seems to be
      lower in real-life heterogeneous patient groups than in homogeneous patient
      samples used in experimental efficacy trials.

PMID- 11846889
TI  - Conceptual framework of public health surveillance and action and its application
      in health sector reform.
AB  - BACKGROUND: Because both public health surveillance and action are crucial, the
      authors initiated meetings at regional and national levels to assess and reform
      surveillance and action systems. These meetings emphasized improved epidemic
      preparedness, epidemic response, and highlighted standardized assessment and
      reform. METHODS: To standardize assessments, the authors designed a conceptual
      framework for surveillance and action that categorized the framework into eight
      core and four support activities, measured with indicators. RESULTS: In
      application, country-level reformers measure both the presence and performance of
      the six core activities comprising public health surveillance (detection,
      registration, reporting, confirmation, analyses, and feedback) and acute
      (epidemic-type) and planned (management-type) responses composing the two core
      activities of public health action. Four support activities - communications,
      supervision, training, and resource provision - enable these eight core
      processes. National, multiple systems can then be concurrently assessed at each
      level for effectiveness, technical efficiency, and cost. CONCLUSIONS: This
      approach permits a cost analysis, highlights areas amenable to integration, and
      provides focused intervention. The final public health model becomes a district
      focused, action-oriented integration of core and support activities with enhanced
      effectiveness, technical efficiency, and cost savings. This reform approach leads
      to sustained capacity development by an empowerment strategy defined as
      facilitated, process-oriented action steps transforming staff and the system.

PMID- 11846890
TI  - Expression and localization of estrogen receptor-beta in annulus cells of the
      human intervertebral disc and the mitogenic effect of 17-beta-estradiol in vitro.
AB  - BACKGROUND: Recent evidence suggests that estrogens exert effects in different
      tissues throughout the body, and that the estrogen receptor beta (ERbeta) may be
      important for the action of estrogen (17-beta-estradiol) on the skeleton. The
      cellular localization of ERbeta in the human intervertebral disc, however, has
      not yet been explored. METHODS: Human disc tissue and cultured human disc cells
      were used for immunocytochemical localization of ERbeta. mRNA was isolated from
      cultured human disc cells, and RT-PCR amplification of ERbeta was employed to
      document molecular expression of this receptor. Cultured human disc cells were
      tested to determine if 17-beta-estradiol stimulated cell proliferation. RESULTS:
      In this report data are presented which provide evidence for ERbeta gene
      expression in human intervertebral disc cells in vivo and in vitro. Culture of
      annulus cells in the presence of 10-7 M 17-beta-estradiol significantly increased
      cell proliferation. CONCLUSIONS: These data provide new insight into the biology
      of cells in the annulus of the intervertebral disc.

PMID- 11846891
TI  - Synthesis and cytotoxicity of a biotinylated CC-1065 analogue.
AB  - BACKGROUND: The use of pretargeting technology for cancer imaging and treatment
      has made significant progress in the last few years. This approach takes
      advantage of the fact that biotin binds strongly to proteins avidin and
      streptavidin. Thus, a non-toxic tumor cell specific antibody is conjugated with
      avidin/streptavidin, and is administered to patients. After the antibody binds to
      tumor cells (usually 24--48 h); a clearing agent is given to remove the residual
      circulating antibodies in blood. Lastly, a toxic biotin-radioisotope conjugate is
      administered. Due to the small size of the biotin-radioisotope molecule and tight
      binding between biotin and avidin/streptavidin, the biotin-radioisotope rapidly
      binds to tumor cells with high specificity. CC-1065 (1) is one of a few classes
      of extremely potent antitumor agents, and a biotinalyted CBI-bearing CC-1065
      analogue is a promising candidate to be used in the pretargeting technology to
      treat cancer. RESULTS: A biotinalyted CBI-bearing CC-1065 analogue, 6, was
      synthesized. The IC50 of 6 was 0.7 nM against U937 cells. Compound 6 caused
      apototsis of U937 cells. CONCLUSIONS: For the first time, a biotinalyted CBI
      bearing CC-1065 analogue, 6, was synthesized. The biotinylated 6 can serve as a
      model compound to explore the usefulness of non-radioactive small molecule
      anticancer drugs in the pretargeting strategy for cancer imaging and therapy.

PMID- 11846892
TI  - Effects of long-term moderate exercise and increase in number of daily steps on
      serum lipids in women: randomised controlled trial [ISRCTN21921919].
AB  - BACKGROUND: This study was designed to evaluate the effects of a 24-month period
      of moderate exercise on serum lipids in menopausal women. METHODS: The subjects
      (40--60 y) were randomly divided into an exercise group (n = 14) and a control
      group (n = 13). The women in the exercise group were asked to participate in a 90
      minute physical education class once a week and to record their daily steps as
      measured by a pedometer for 24 months. RESULTS: Mean of daily steps was
      significantly higher in the exercise group from about 6,800 to over 8,500 steps
      (P < 0.01). In the control group, the number of daily steps ranged from 5,700 to
      6,800 steps throughout the follow-up period. A significant interaction between
      the exercise group and the control group in the changes og total cholesterol
      (TC), high-density lipoprotein cholesterol (HDLC) and TC : HDLC ratio could be
      observed (P < 0.05). By multiple regression analysis, the number of daily steps
      was related to HDLC and TC : HDLC levels after 24 months, and the changes in TC
      and HDLC concentrations. CONCLUSIONS: These results suggest that daily exercise
      as well as increasing the number of daily steps can improve the profile of serum
      lipids.

PMID- 11846893
TI  - Prediction models in the design of neural network based ECG classifiers: a neural
      network and genetic programming approach.
AB  - BACKGROUND: Classification of the electrocardiogram using Neural Networks has
      become a widely used method in recent years. The efficiency of these classifiers
      depends upon a number of factors including network training. Unfortunately, there
      is a shortage of evidence available to enable specific design choices to be made
      and as a consequence, many designs are made on the basis of trial and error. In
      this study we develop prediction models to indicate the point at which training
      should stop for Neural Network based Electrocardiogram classifiers in order to
      ensure maximum generalisation. METHODS: Two prediction models have been
      presented; one based on Neural Networks and the other on Genetic Programming. The
      inputs to the models were 5 variable training parameters and the output indicated
      the point at which training should stop. Training and testing of the models was
      based on the results from 44 previously developed bi-group Neural Network
      classifiers, discriminating between Anterior Myocardial Infarction and normal
      patients. RESULTS: Our results show that both approaches provide close fits to
      the training data; p = 0.627 and p = 0.304 for the Neural Network and Genetic
      Programming methods respectively. For unseen data, the Neural Network exhibited
      no significant differences between actual and predicted outputs (p = 0.306) while
      the Genetic Programming method showed a marginally significant difference (p =
      0.047). CONCLUSIONS: The approaches provide reverse engineering solutions to the
      development of Neural Network based Electrocardiogram classifiers. That is given
      the network design and architecture, an indication can be given as to when
      training should stop to obtain maximum network generalisation.

PMID- 11846894
TI  - Meningioma radiosurgery: tumor control, outcomes, and complications among 190
      consecutive patients.
AB  - OBJECTIVE: To determine local control (LC) and complication rates for patients
      with intracranial meningiomas who underwent radiosurgery. METHODS: One hundred
      ninety consecutive patients with 206 meningiomas underwent radiosurgery between
      1990 and 1998. One hundred forty-seven tumors (77%) involved the cranial base.
      The median age at the time of radiosurgery was 58 years (range, 20-90 yr). There
      were 126 female patients (66%). One hundred twelve patients (59%) had undergone
      one or more previous operations (median, 1; range, 1-5). Twenty-two patients
      (12%) had either atypical (n = 13) or malignant (n = 9) tumors. The median
      prescription isodose volume was 8.2 cm(3) (range, 0.5-50.5 cm(3)), and the median
      tumor margin dose was 16 Gy (range, 12-36 Gy). The median imaging and clinical
      follow-up periods were 40 and 47 months, respectively. RESULTS: Overall survival
      rates for the entire cohort at 5 and 7 years were 82 and 82%, respectively; cause
      specific survival rates at 5 and 7 years were 94 and 92%, respectively. The cause
      specific survival rates at 5 years for patients with benign, atypical, and
      malignant tumors were 100, 76, and 0%, respectively (P < 0.0001). The 5-year LC
      rate was 89%, with 114 tumors (56%) decreasing in size. LC rates were correlated
      with tumor histological features (P < 0.0001); patients with benign tumors
      exhibited a 5-year LC rate of 93%, compared with 68 and 0% for patients with
      atypical or malignant meningiomas, respectively. No correlation was observed
      between radiation dose and LC rate. Twenty-four patients (13%) experienced
      treatment-related complications, including cranial nerve deficits (8%),
      symptomatic parenchymal changes (3%), internal carotid artery stenosis (1%), and
      symptomatic cyst formation (1%). Only six patients (3%) exhibited decreases in
      functional status that were directly related to radiosurgery. Tumor volume, tumor
      margin dose, or previous radiotherapy was not associated with the development of
      radiation-related complications. CONCLUSION: Radiosurgery is an effective
      management strategy for many patients with meningiomas. Patients with atypical or
      malignant tumors exhibit high recurrence rates despite the use of radiosurgery,
      and these patients continue to exhibit worse cause-specific survival rates
      despite aggressive treatment, including surgery, external-beam radiotherapy, and
      radiosurgery. Further study is needed to determine the tumor control and
      complication rates 10 years or more after meningioma radiosurgery.

PMID- 11846895
TI  - Association between intracranial plasmacytoma and multiple myeloma:
      clinicopathological outcome study.
AB  - OBJECTIVE: Intracranial plasmacytomas are rare lesions that can arise from the
      calvarium, dura, or cranial base and exhibit a benign course unless associated
      with myeloma. Attention has recently been focused on the role of the cell
      adhesion molecules CD56 and CD31 in the pathogenesis of myeloma. No such
      information is available for intracranial plasmacytomas and myeloma-associated
      lesions. METHODS: We investigated the relationship between CD56 and CD31
      expression, intracranial location, and progression to myeloma for a series of
      nine intracranial plasmacytomas (three dural, one calvarial, and five cranial
      base lesions). These parameters were also correlated with proliferation indices,
      as assessed by MIB-1 immunostaining of the histological sections. A single
      pathologist (AO) performed immunohistochemical analyses and reviewed all slides.
      RESULTS: Intracranial plasmacytomas presented more commonly in female patients
      (89%). The three dural lesions were CD56- and CD31-negative and exhibited MIB-1
      staining of less than 10%; no patient developed myeloma or recurrence. Of the
      five cranial base lesions, three were CD56-positive, none was CD31-positive, and
      two exhibited MIB-1 labeling of more than 45%, with plasmablastic morphological
      features. Compared with other intracranial plasmacytomas, five of five patients
      with cranial base lesions developed bone marrow biopsy-proven myeloma (P < 0.05)
      within 8 months. The calvarial lesion was CD56- and CD31-positive, and the
      patient developed myeloma soon after diagnosis. Both of the two highly
      proliferative plasmablastic lesions recurred, one after gross total resection
      without radiotherapy and the other after a biopsy and 2000-cGy radiotherapy.
      CONCLUSION: Among intracranial plasmacytomas, cranial base location was the
      strongest predictor of the development of multiple myeloma. Expression of the
      cell adhesion molecules CD31 and CD56 was not predictive of outcome.
      Extramedullary dural-based lesions were CD56-negative and were not associated
      with myeloma. A high proliferation index and plasmablastic morphological features
      were predictive of a short time to recurrence and aggressive behavior. We
      recommend 4050- to 5040-cGy fractionated radiotherapy for all intracranial plasma
      cell neoplasms and gross total resection for non-cranial base lesions.

PMID- 11846896
TI  - Peritumoral brain edema in intracranial meningiomas: effects of radiological and
      histological factors.
AB  - OBJECTIVE: We examined the radiological and histological features influencing the
      development of peritumoral brain edema (PTBE) among patients with meningiomas.
      METHODS: Factors causing PTBE were retrospectively analyzed for 125 patients with
      primary intracranial meningiomas. These factors included tumor size, tumor
      location, brain-tumor interface, signal intensity on T2-weighted scans, contrast
      enhancement, and cyst formation (as observed on magnetic resonance imaging
      scans), as well as tumor vascularity and blood supply (as observed in digital
      subtraction angiography studies). We defined the edema/tumor volume ratio as the
      edema index, and we used this index to evaluate PTBE. RESULTS: A relationship
      between the tumor size and the volume of PTBE was observed. Convexity and middle
      fossa meningiomas demonstrated the greatest increases in mean edema indices.
      Meningothelial, anaplastic, microcystic, and angiomatous subtypes exhibited
      higher edema indices than did other types. Multivariate analysis demonstrated two
      significant radiological factors: cortical penetration (as defined by the
      disappearance of the arachnoid layer on magnetic resonance imaging scans)
      (relative risk, 2.067; P = 0.0148) and vascular supply from the pial-cortical
      arteries (as observed on angiograms) (relative risk, 2.087; P = 0.0082).
      CONCLUSION: Tumor infiltration into adjacent brain parenchyma and a pial-cortical
      blood supply are critical factors for the development of PTBE among patients with
      meningiomas.

PMID- 11846897
TI  - Memory deficits among children with craniopharyngiomas.
AB  - OBJECTIVE: To describe neuropsychological functioning (with a specific focus on
      cognition and memory) after surgical treatment of craniopharyngiomas. METHODS:
      Sixteen patients who were between 6 and 15 years of age at the time of surgery
      comprised the sample. Each child had been treated for a craniopharyngioma with
      surgery only, on Dana-Farber Cancer Institute Protocol 92-077. RESULTS: The
      overall level of cognitive functioning was well within the average range, with
      both language and visuospatial functioning being generally intact; however,
      specific memory problems, in both the language and visuospatial domains, were
      evident. CONCLUSION: Although general cognitive functioning was intact after the
      surgical treatment of craniopharyngiomas, difficulties in the retrieval of
      learned information were observed. Neuropsychological assessments, with a focus
      on memory recall, should be a component of the medical management plan for each
      child.

PMID- 11846898
TI  - Outcomes after aneurysm rupture during endovascular coil embolization.
AB  - OBJECTIVE: Intracranial aneurysm rupture during placement of Guglielmi detachable
      coils has been reported, but the management and consequences of this event have
      not been extensively described. We present our experience with this feared
      complication and report possible neuroradiological and neurosurgical
      interventions to improve outcomes. METHODS: We retrospectively reviewed the
      records for 701 patients with 734 intracranial aneurysms that were treated with
      endovascular coiling, during a 6-year period, in the metropolitan Minneapolis-St.
      Paul (Minnesota) area. This analysis revealed 10 cases of perforation during
      coiling. The management and outcomes were recorded, and the pertinent literature
      was reviewed. RESULTS: All 10 cases involved previously ruptured aneurysms. This
      complication occurred sporadically and was not observed in the first 100 cases.
      Perforation occurred during microcatheterization of the aneurysm in two cases and
      during coil deposition in eight cases. Seven of the perforated aneurysms were
      located in the anterior circulation and three in the posterior circulation. Six
      of the 10 patients made good or fair recoveries; all three patients with
      posterior circulation lesions died immediately after rehemorrhage. Elevated
      intracranial pressure (ICP) was noted for all five patients with intraventricular
      catheters in place. Bilateral pupil dilation and profound hemodynamic changes
      were noted for eight patients. Coiling was rapidly completed, and total or nearly
      total occlusion was achieved in all cases. Emergency ventriculostomy was
      performed to rapidly reduce increased ICP for two patients, both of whom made
      good recoveries. Hemodynamic and angiographic factors after perforation, such as
      prolonged systemic hypertension, persistent dye extravasation after deployment of
      the first Guglielmi detachable coil, and persistent prolongation of contrast dye
      transit time (suggesting ongoing ICP elevation), were correlated with poor
      outcomes. CONCLUSION: Previously ruptured aneurysms seem to be more susceptible
      to endovascular treatment-related perforation than are unruptured lesions. Worse
      prognoses are associated with iatrogenic rupture during coiling of posterior
      circulation lesions, compared with those in the anterior circulation. When
      perforation is recognized, the definitive treatment seems to be reversal of
      anticoagulation therapy and completion of Guglielmi detachable coil embolization.
      Immediate neurosurgical intervention is limited in these cases and focuses on
      decreasing ICP via emergency ventriculostomy. However, these measures may be life
      saving, and neurosurgical assistance must be readily available during treatment
      of these cases.

PMID- 11846899
TI  - Blood transfusion during aneurysm surgery.
AB  - INTRODUCTION: Increasing costs and concerns about blood supply safety have led to
      a reevaluation of blood transfusion practices. This study was undertaken to
      examine blood use during aneurysm surgery. METHODS: We performed a retrospective
      analysis of hospital records including operative, anesthetic, and nursing notes,
      computed tomographic scans, and four-vessel angiographic films of 547 patients
      undergoing surgery for ruptured and unruptured cerebral aneurysms at Harborview
      Medical Center in Seattle. During the review period, the transfusion threshold
      was not altered. RESULTS: A total of 134 patients (24.5%) received an
      intraoperative blood transfusion (median number of units, 2; range, 1-17).
      Preoperative factors associated with intraoperative blood use included older
      patient age (P < 0.001), lower hematocrit level on admission (P = 0.007),
      ruptured rather than unruptured aneurysm (P = 0.004), severe intraventricular
      hemorrhage (P = 0.03), and larger aneurysm size (P = 0.004). Factors not
      associated with intraoperative blood transfusion included past medical history
      (including cardiac or pulmonary disease), admission clinical grade after aneurysm
      rupture, findings such as hydrocephalus on computed tomographic scanning, and
      aneurysm location and aneurysm neck-to-fundus ratio. Also associated with blood
      transfusion during surgery were intraoperative aneurysm rupture (P < 0.0001),
      intracerebral hematoma evacuation (P = 0.02), and obliteration of multiple
      aneurysms (P = 0.002). Among patients who received an intraoperative transfusion,
      those who experienced an aneurysm rupture required an average of 3.6 +/- 0.35
      units, whereas patients who did not have a rupture required 1.9 +/- 0.12 units (P
      = 0.001). Postoperatively, a total of 244 patients (44.6%), including 77 who
      received blood intraoperatively, required a blood transfusion (median number of
      units, 2; range, 1-31). Postoperative blood transfusion was associated with the
      treatment of patients with subarachnoid hemorrhage (P < 0.0001), particularly
      among poor-grade patients who developed medical complications. CONCLUSION: Blood
      transfusion can be expected in one in five patients undergoing aneurysm surgery.
      Reducing intraoperative rupture may reduce the need for blood products.

PMID- 11846901
TI  - Implications of excessive fibrinolysis and alpha(2)-plasmin inhibitor deficiency
      in patients with severe head injury.
AB  - OBJECTIVE: To evaluate the involvement of the fibrinolytic system, especially
      focused on alpha(2)-plasmin inhibitor, in patients with head injury. METHODS:
      This study consisted of 47 patients with isolated blunt head trauma in whom blood
      sampling could be initiated within 3 hours after injury. Patients were divided
      into two groups according to Glasgow Outcome Scale score status at 3 months after
      injury. In Group 1 patients (n = 26), the outcome was characterized as good
      recovery or moderate disability; in Group 2 patients (n = 21), the outcome was
      characterized as severe disability, vegetative state, or death. RESULTS:
      Concentrations of thrombin-antithrombin III complex were greater than 100
      microg/L in 39 of 47 patients, and concentrations in Group 2 patients were
      elevated significantly beyond the concentrations in Group 1 patients. Activities
      of alpha(2)-plasmin inhibitor in Group 2 were significantly lower than in Group 1
      (P < 0.0001). In Group 1 patients, alpha(2)-plasmin inhibitor activity was
      greater than 60%, while in all but four Group 2 patients, the inhibitor was
      reduced to less than 60% of normal activity within 3 hours of injury. All
      patients with alpha(2)-plasmin inhibitor activity less than 60% showed a marked
      bleeding tendency and/or severe brain edema. Using sandwich enzyme-linked
      immunosorbent assay, fibrinogen degradation product and fibrin degradation
      product were measured separately. A significant correlation was apparent between
      thrombin-antithrombin III complex and fibrinogen degradation product, as well as
      between the complex and fibrin degradation product. Marked decreases in alpha(2)
      plasmin inhibitor were noted only in patients with thrombin-antithrombin III
      complex concentrations exceeding 500 microg/L. CONCLUSION: Fibrinolysis and
      fibrinogenolysis may be involved according to the degree of coagulation
      activation in the pathophysiology of severe head injury. Decreased activity of
      alpha(2)-plasmin inhibitor indicated poor prognosis and may be an exacerbating
      factor in the acute phase of head trauma.

PMID- 11846902
TI  - Analysis of hypertrophy of the posterior longitudinal ligament of the cervical
      spine, on the basis of clinical and experimental studies.
AB  - OBJECTIVE: The goal of this study was to elucidate the pathophysiological
      features and treatment of hypertrophy of the posterior longitudinal ligament
      (HPLL) of the cervical spine. HPLL is defined as a pathological thickening of the
      posterior longitudinal ligament (PLL), causing spinal cord compression.
      Incomplete decompression via removal of only coexisting herniated intervertebral
      discs or spondylotic spurs might be performed, resulting in unsatisfactory
      surgical outcomes, when the PLL becomes abnormally thickened and contributes to
      myelopathy. METHODS: Patients with HPLL who underwent cervical decompression
      surgery were selected. Medical records and radiographs were retrospectively
      reviewed, to obtain data on the pre- and postoperative clinical conditions of the
      patients. Autopsy cases with HPLL proven by low-energy x-ray examinations were
      chosen for assessment of the pathological characteristics. RESULTS: Seventeen men
      and three women with HPLL underwent treatment via an anterior approach, with
      direct removal of HPLL. Nineteen patients developed myelopathy, whereas one
      patient developed radiculopathy. Radiologically, all HPLL cases exhibited
      coexisting herniated intervertebral discs and 10 exhibited small segmental
      ossifications of the PLL. Magnetic resonance imaging or computed tomographic
      myelography revealed extensive cord compression across the vertebral endplate
      level. The average preoperative Benzel modified Japanese Orthopaedic Association
      score was 10.8, and the average postoperative score was 13.2. Histological
      examinations revealed thickening of the PLL with proliferation of chondrocytes,
      together with various degenerative changes. CONCLUSION: Patients with HPLL can
      benefit from an anterior approach with direct removal of the HPLL and associated
      herniated intervertebral discs or ossification of the PLL. Cervical
      polytomography, computed tomography, and magnetic resonance imaging are useful in
      establishing a diagnosis of HPLL.

PMID- 11846900
TI  - Serum S100B protein levels are correlated with subclinical neurocognitive
      declines after carotid endarterectomy.
AB  - OBJECTIVE: Carotid endarterectomy (CEA) is an effective means of stroke
      prevention among appropriately selected patients; however, neuropsychometric
      testing has revealed subtle cognitive injuries in the early postoperative period.
      The purpose of this study was to establish whether serum levels of two
      biochemical markers of cerebral injury were correlated with postoperative
      declines in neuropsychometric test performance after CEA. METHODS: Fifty-five
      consecutive patients underwent a battery of neuropsychometric tests 24 hours
      before and 24 hours after elective CEA. Two patients were excluded because of
      postoperative strokes. The pre- and postoperative serum levels of S100B protein
      and neuron-specific enolase for injured patients, defined as those who exhibited
      significant declines in neuropsychometric test performance (n = 12), were
      compared with the levels for uninjured patients (n = 41). RESULTS: There were no
      significant differences in the baseline S100B levels for the two groups. Injured
      patients exhibited significantly higher S100B levels, compared with uninjured
      patients, at 24, 48, and 72 hours after surgery (P < 0.05). There were no
      significant differences in neuron-specific enolase levels for injured and
      uninjured patients at any time point. CONCLUSION: These data suggest that subtle
      cerebral injuries after CEA, even in the absence of overt strokes, are associated
      with significant increases in serum S100B but not neuron-specific enolase levels.
      Analyses of earlier time points in future studies of subtle cognitive injuries
      and biochemical markers of cerebral injury after CEA may be revealing.

PMID- 11846903
TI  - Association of Chiari I malformation, mental retardation, speech delay, and
      epilepsy: a specific disorder?
AB  - OBJECTIVE: The Chiari I malformation is defined as tonsillar herniation of at
      least 3 to 5 mm below the foramen magnum. Although Chiari I malformation is
      considered to derive from a mesodermal disorder resulting in underdevelopment of
      the posterior fossa relative to its content, evidence for a possible
      heterogeneous etiology also has been reported. The aim of the present study is to
      elucidate the relationship between Chiari I malformation and mental retardation,
      speech delay, and epilepsy to consider a possible specific pathogenetic
      background. METHODS: Thirty-five patients with Chiari I malformations were
      identified by use of magnetic resonance imaging during a period between 1993 and
      1999. The study consisted of nine patients (four boys and five girls) who were
      affected by mental retardation, speech delay, and epilepsy. All patients
      underwent electroencephalography and brain and cervical spine magnetic resonance
      imaging. RESULTS: All patients were mentally retarded with a mean intelligence
      quotient of 50. Seven patients had a positive history for speech delay, and five
      were epileptic. Electroencephalograms demonstrated abnormalities in seven
      patients. The mean tonsillar displacement was 10.1 mm. A thin corpus callosum and
      a wide cavum septum pellucidum were present in three patients. Neither
      hydromyelia nor scoliosis was observed. No correlation between the degree of the
      ectopia and clinical manifestation was noted. CONCLUSION: The association of
      Chiari I malformation with epilepsy, speech delay, and mental retardation may not
      be a mere incidental finding but may be a marker for a different pathogenetic
      background.

PMID- 11846904
TI  - Percutaneous transpedicular polymethylmethacrylate vertebroplasty for the
      treatment of spinal compression fractures.
AB  - OBJECTIVE: To assess the safety, feasibility, and clinical outcome of
      percutaneous transpedicular polymethylmethacrylate vertebroplasty (PTPV) for the
      treatment of spinal compression fractures causing refractory pain. METHODS: We
      retrospectively reviewed a consecutive group of patients undergoing PTPV at our
      institution between April 1998 and January 2001. Outcome measures included
      analgesic requirements, ambulatory status, sleep comfort, and overall quality of
      life 2 weeks after the procedure. RESULTS: A total of 97 patients (73 women and
      24 men) underwent 258 PTPV procedures during 133 treatment sessions. The mean age
      was 76 years (range, 42-99 yr). The mean duration of follow-up was 14.7 months
      (range, 2-35 mo). Most of the patients had osteoporotic compression fractures,
      although some had osteolytic malignancies. Complete follow-up was obtained in 81
      patients (84%). Narcotic and analgesic usage decreased in 63% of patients,
      increased in 7%, and remained the same in 30%. Ambulation and mobility were
      improved in 51%, worse in 1% and the same in 48%. One-half of the patients were
      able to sleep more comfortably after the procedure, whereas the other half
      remained the same. Most patients who reported no change in sleep or ambulation
      had experienced no impairment of these activities before PTPV. Overall, 74% of
      patients believed that PTPV significantly enhanced their quality of life and 26%
      reported no change. No patient was worse after PTPV. One patient with preexisting
      pneumonia died of respiratory failure after the procedure; another died of an
      acute stroke weeks later. One patient developed symptomatic pulmonary embolism of
      cement, and another developed transient quadriceps weakness from radiculopathy.
      Other complications were minor and infrequent. There were no infections.
      CONCLUSION: PTPV provided significant relief in a high percentage of patients
      with refractory pain. PTPV is a safe and feasible treatment for patients with
      spinal compression fractures.

PMID- 11846905
TI  - Infratentorial supracerebellar approach to the colloid cysts of the third
      ventricle.
AB  - OBJECTIVE: The transcallosal and the frontal transcortical approaches are the
      most widely used methods in surgery of third ventricle colloid cysts. However,
      these approaches require traction of the frontal lobe and dissection of the
      corpus callosum or corticotomy and involve some postoperative consequences. The
      rationale of the proposed method is to remove the colloid cyst by the
      infratentorial supracerebellar approach and the posterior wall of the third
      ventricle without dissection of any neural structures. METHODS: Five patients
      with a colloid cyst of the third ventricle were operated on by the proposed
      method. The first patient presented with several months' history of symptoms that
      included increased intracranial pressure and right-sided cerebellar signs, caused
      by a metastatic tumor of the right cerebellar hemisphere. The other four patients
      had symptoms including intracranial hypertension for an extended period of time
      without any other neurological deficits. In all patients, magnetic resonance
      imaging revealed a colloid cyst of the third ventricle without hydrocephalus.
      TECHNIQUE: With the infratentorial supracerebellar approach, the arachnoid of the
      quadrigeminal cistern is dissected. The pineal body is separated and displaced
      from the internal vein medially, and the posterior velum interpositum is opened.
      Perforation of the inferior layer of the tela choroidea just above the
      suprapineal recess allows opening of the third ventricle cavity. A foraminal
      region is exposed after a slight lateral displacement of medial surfaces of the
      thalamus along the third ventricle roof. CONCLUSION: The proposed approach
      through the infratentorial supracerebellar space and the posterior wall of the
      third ventricle may be used for removal of colloid cysts, especially in patients
      in whom the lateral ventricles are not enlarged.

PMID- 11846906
TI  - Intrinsic spinal cord tumor resection.

PMID- 11846907
TI  - Anterior cervical vertebrectomy: tips and traps.

PMID- 11846908
TI  - Intraoperative magnetic resonance imaging to determine the extent of resection of
      pituitary macroadenomas during transsphenoidal microsurgery.
AB  - OBJECTIVE: Well-established surgical goals for pituitary macroadenomas include
      gross total resection for noninvasive tumors and debulking with optic chiasm
      decompression for invasive tumors. In this report, we examine the safety,
      reliability, and outcome of intraoperative magnetic resonance imaging (iMRI) used
      to assess the extent of resection, and thus the achievement of preoperative
      surgical goals, during transsphenoidal microneurosurgery. METHODS: Our magnetic
      resonance operating room contains a Hitachi AIRIS II 0.3-T, vertical-field open
      magnet (Hitachi Medical Systems America, Inc., Twinsburg, OH). A motorized
      scanner tabletop moves the patient between the imaging and operative positions.
      For transsphenoidal surgery, the patient is positioned directly on the scanner
      tabletop so that the surgical field is located between 1.2 and 1.6 m from the
      magnet isocenter. At this location, the magnetic field strength is low (<20 G),
      thus permitting the use of many conventional surgical instruments. Thirty
      consecutive patients with pituitary macroadenomas underwent tumor resection in
      our magnetic resonance operating room by use of a standard transsphenoidal
      approach. After initial resection, the patient was advanced into the scanner for
      imaging. If residual tumor was demonstrated and deemed surgically accessible, the
      patient underwent immediate re-exploration. RESULTS: iMRI was performed
      successfully in all 30 patients. In one patient, iMRI was used to clarify the
      significance of hemorrhage from the sellar region and resulted in immediate
      conversion of the procedure to a craniotomy. In the remaining 29 patients,
      initial iMRI demonstrated that the endpoint for extent of resection had been
      achieved in only 10 patients (34%) after an initial resection attempt, whereas 19
      patients (66%) still had unacceptable residual tumor. All 19 of these latter
      patients underwent re-exploration. Ultimately, re-exploration resulted in the
      achievement of the planned endpoint for extent of resection in all of the 29
      completed transsphenoidal explorations. Operative time was extended in all cases
      by at least 20 minutes. CONCLUSION: iMRI can be used to safely, reliably, and
      objectively assess the extent of resection of pituitary macroadenomas during the
      transsphenoidal approach. The surgeon is frequently surprised by the extent of
      residual tumor after an initial resection attempt and finds the intraoperative
      images useful for guiding further resection.

PMID- 11846909
TI  - Methodological and technical issues for integrating functional magnetic resonance
      imaging data in a neuronavigational system.
AB  - OBJECTIVE: The aim of this article was to analyze the technical and
      methodological issues resulting from the use of functional magnetic resonance
      image (fMRI) data in a frameless stereotactic device for brain tumor or pain
      surgery (chronic motor cortex stimulation). METHODS: A total of 32 candidates, 26
      for brain tumor surgery and six chronic motor cortex stimulation, were studied by
      fMRI scanning (61 procedures) and intraoperative cortical brain mapping under
      general anesthesia. The fMRI data obtained were analyzed with the Statistical
      Parametric Mapping 99 software, with an initial analysis threshold corresponding
      to P < 0.001. Subsequently, the fMRI data were registered in a frameless
      stereotactic neuronavigational device and correlated to brain mapping. RESULTS:
      Correspondence between fMRI-activated areas and cortical mapping in primary motor
      areas was good in 28 patients (87%), although fMRI-activated areas were highly
      dependent on the choice of paradigms and analysis thresholds. Primary sensory-
      and secondary motor-activated areas were not correlated to cortical brain
      mapping. Functional mislocalization as a result of insufficient correction of the
      echo-planar distortion was identified in four patients (13%). Analysis thresholds
      (from P < 0.0001 to P < 10(-12)) more restrictive than the initial threshold (P <
      0.001) had to be used in 25 of the 28 patients studied, so that fMRI motor data
      could be matched to cortical mapping spatial data. These analysis thresholds were
      not predictable preoperatively. Maximal tumor resection was accomplished in all
      patients with brain tumors. Chronic motor cortex electrode placement was
      successful in each patient (significant pain relief >50% on the visual analog
      pain scale). CONCLUSION: In brain tumor surgery, fMRI data are helpful in
      surgical planning and guiding intraoperative brain mapping. The registration of
      fMRI data in anatomic slices or in the frameless stereotactic neuronavigational
      device, however, remained a potential source of functional mislocalization.
      Electrode placement for chronic motor cortex stimulation is a good indication to
      use fMRI data registered in a neuronavigational system and could replace
      somatosensory evoked potentials in detection of the central sulcus.

PMID- 11846910
TI  - The Camino intracranial pressure sensor: is it optimal technology? An internal
      audit with a review of current intracranial pressure monitoring technologies.
AB  - OBJECTIVE: To audit the reliability of the Camino intracranial pressure (ICP)
      sensor (Camino Laboratories, San Diego, CA) in our clinical practice as part of a
      continuing quality assurance program, and to assess its relative usefulness as
      compared with currently available ICP monitoring technologies that we reviewed.
      DESIGN: Prospective audit of ICP device reliability and function in 50 patients
      with head injuries. METHODS: Zero drift was recorded immediately after the ICP
      device was removed from the patient. Dynamic frequency response bench testing of
      each functioning catheter from 0 to 30 Hz and static calibration testing from 0
      to 100 mmHg during environmental temperature variation from 22 to 40 degrees C
      were carried out. RESULTS: Zero drift (range, -13 to 22 mmHg; median, -1 mmHg)
      was recorded immediately after the devices were removed from patients. Seventeen
      (50%) of the devices tested for zero drift had absolute drifts of at least 3
      mmHg. There was no correlation between recorded zero drift and duration of
      monitoring (r = 0.154, P = 0.207). Five sensors (10% of those tested) failed
      during patient monitoring and were replaced. Static and dynamic calibration tests
      of the functioning sensors were within the manufacturer's specifications.
      However, the sensitivity of the devices to environmental temperature remains a
      problem. CONCLUSION: The Camino ICP sensor remains one of the most popular ICP
      monitoring devices for use in patients with traumatic brain injuries. However,
      our recent in-house assessment demonstrated the robustness of the device to be
      less than adequate during routine practice. In this study, more than 50%
      exhibited zero drift greater than 3 mmHg, which is unacceptable in a catheter tip
      ICP monitoring device in which zero drift and calibration cannot be checked in
      vivo. A review of the literature revealed that other available ICP monitoring
      devices may prove to be more reliable and thus more appropriate for routine
      clinical measurement of ICP.

PMID- 11846911
TI  - Idiopathic normal pressure hydrocephalus: a systematic review of diagnosis and
      outcome.
AB  - OBJECTIVE: Patient selection for cerebrospinal fluid diversion is difficult,
      because idiopathic normal pressure hydrocephalus (INPH) mimics other
      neurodegenerative disorders and no findings reliably predict outcome. The
      literature was reviewed to identify diagnostic criteria that predict shunt
      response and to formulate prognostic expectations. METHODS: MEDLINE was searched,
      and 44 articles meeting predetermined criteria were included. RESULTS: Clinical
      series were frequently retrospective with small patient numbers and
      unstandardized outcome evaluation. Clinical findings suggestive of shunt
      responsiveness were the complete triad (gait disturbance, urinary incontinence,
      and dementia) with early gait disturbance. Degree of hydrocephalus was not
      correlated with clinical improvement. Reduction of the subcortical low-blood flow
      area was correlated with improvement in three small studies. Clinical response to
      prolonged cerebrospinal fluid drainage predicted shunt outcome in all cases in
      two small series. Overall, 59% (range, 24-100%) of patients improved after
      shunting, and 29% (range, 10-100%) of patients experienced prolonged improvement.
      Complications occurred in 38% (range, 5-100%) of patients, additional surgery was
      required in 22% (range, 0-47%) of patients, and there was a 6% (range, 0-35%)
      combined rate of permanent neurological deficit and death. CONCLUSION: Shunting
      INPH is associated with an approximately 29% rate of significant improvement and
      a 6% significant complication rate. Enlargement of the subcortical low-flow area
      and clinical improvement secondary to prolonged lumbar drainage may provide
      additive predictive value above clinical and computed tomographic criteria. A
      multicenter clinical trial that focuses on the value of ancillary tests, defines
      the clinical course of a patient with a ventriculoperitoneal shunt, and evaluates
      the cost effectiveness of shunting INPH is needed to better describe outcome from
      shunting in INPH.

PMID- 11846912
TI  - Biodegradable polyglycolide endovascular coils promote wall thickening and drug
      delivery in a rat aneurysm model.
AB  - OBJECTIVE: We designed biodegradable polyglycolide coils (BPCs) and compared the
      histopathological response to the coils with that to platinum Guglielmi
      detachable coils (GDCs), after insertion into ligated common carotid arteries
      (CCAs) of adult rats. BPCs were also tested for use in local drug delivery.
      METHODS: Segments (4-mm) of unmodified BPCs, unmodified GDCs, or BPCs coated with
      Type I bovine collagen and recombinant human vascular endothelial growth factor
      165 (500 microg/ml) were inserted into ligated CCAs of adult rats for 14 days,
      and specimens were compared with contralateral CCA control specimens. RESULTS:
      Arterial segments with BPCs exhibited substantially increased wall thickening,
      compared with GDCs (0.33 mm versus 0.10 mm, P < 0.005), which reduced the luminal
      diameter by 40%, relative to untreated contralateral control specimens (P < 0.05,
      n = 6). Arterial segments with BPCs also exhibited a marked reduction (P < 0.05,
      n = 6) in luminal area (0.72 +/- 0.93 mm(2)), with marked cellular proliferation
      within the coil diameter, indicating coil integration. Arterial segments with
      collagen/recombinant human vascular endothelial growth factor-coated BPCs also
      exhibited a marked 2.9-fold increase (P < 0.005, n = 5) in wall thickness (0.29
      +/- 0.11 mm) and a 34% reduction in luminal diameter, compared with contralateral
      control vessels. There was marked proliferation of cells within the coil lumen of
      vessels treated with BPCs with collagen/recombinant human vascular endothelial
      growth factor. CONCLUSION: In this feasibility study, BPCs enhanced the vascular
      response of CCA segments, compared with GDCs, and were also suitable for local
      protein delivery to the vessel lumen, under conditions of stasis and arterial
      pressurization of vascular cells.

PMID- 11846913
TI  - Treatment of traumatic brain injury in female rats with intravenous
      administration of bone marrow stromal cells.
AB  - OBJECTIVE: To study the effect of bone marrow stromal cells administered
      intravenously to female rats subjected to traumatic brain injury. METHODS: We
      injected marrow stromal cells harvested from male rat bone marrow (n = 24) into
      the tail vein of the female rat (n = 8) 24 hours after traumatic brain injury;
      the rats were killed at Day 7 or 14 after treatment. The neurological function of
      the rats was evaluated using the rotarod test and the neurological severity
      score. The distribution of the male donor cells in brain, heart, lung, kidney,
      liver, muscle, spleen, and bone marrow of the female recipient rats was measured
      by identifying Y chromosome-positive cells using fluorescent in situ
      hybridization. RESULTS: We found that marrow stromal cells injected intravenously
      significantly reduced motor and neurological deficits compared with control
      groups by Day 15 after traumatic brain injury (P < 0.05, analysis of covariance
      for repeated measures). The transplanted cells preferentially engrafted into the
      parenchyma of the injured brain and expressed the neuronal marker NeuN and the
      astrocytic marker glial fibrillary acidic protein. Marrow stromal cells were also
      found in other organs in female rats subjected to traumatic brain injury without
      any obvious adverse effects. CONCLUSION: These data suggest that the intravenous
      administration of marrow stromal cells may be a promising therapeutic strategy
      that warrants further investigation for patients with traumatic brain injury.

PMID- 11846914
TI  - The novel 5-lipoxygenase inhibitor ABT-761 attenuates cerebral vasospasm in a
      rabbit model of subarachnoid hemorrhage.
AB  - OBJECTIVE: Eicosanoids have been implicated in the pathogenesis of cerebral
      vasospasm after subarachnoid hemorrhage (SAH). Leukotrienes, 5
      hydroxyperoxyeicosatetraenoic acid, and 5-hydroxyeicosatetraenoic acid are part
      of this group of substances, resulting from the 5-lipoxygenase activity on
      arachidonic acid metabolism. This study examined the effects of ABT-761, a new 5
      lipoxygenase inhibitor, on cerebral vasospasm in an in vivo rabbit model of SAH.
      METHODS: A total of 48 rabbits were assigned to one of six groups: SAH + placebo
      (n = 8), SAH + ABT-761 20 mg/kg (n = 8), SAH + ABT-761 30 mg/kg (n = 8), control
      + placebo (n = 8), control + ABT-761 20 mg/kg (n = 8), and control + ABT-761 30
      mg/kg (n = 8). Drug administration was initiated 30 minutes after induction of
      SAH and repeated 24 hours later. The animals were killed 48 hours after SAH,
      using the perfusion-fixation method. The cross sectional areas of basilar artery
      histological sections were measured by an investigator blinded to the treatment
      groups of the individual samples. RESULTS: In placebo-treated animals, the
      average luminal cross sectional area of the basilar artery was reduced by 68%
      after SAH as compared with controls (P < 0.0001). After SAH, the vasospastic
      response was attenuated in animals treated with 20 or 30 mg/kg representing a 28
      or 35% reduction, respectively (P = 0.0011 and P = 0.0038). CONCLUSION: The
      results demonstrated that ABT-761 is effective in attenuating experimental
      cerebral vasospasm, indicating that this new drug represents a potential
      therapeutic agent for the treatment of vasospasm after SAH.

PMID- 11846915
TI  - Cerebral venous blood outflow: a theoretical model based on laboratory
      simulation.
AB  - OBJECTIVE: The cerebrovascular bed and cerebrospinal fluid circulation have been
      modeled extensively except for the cerebral venous outflow, which is the object
      of this study. METHODS: A hydraulic experiment was designed for perfusion of a
      collapsible tube in a pressurized chamber to simulate the venous outflow from the
      cranial cavity. CONCEPT: The laboratory measurements demonstrate that the
      majority of change in venous flow can be attributed to either inflow pressure
      when the outflow is open, or the upstream transmural pressure when outflow is
      collapsed. On this basis, we propose a mathematical model for pressure
      distribution along the venous outflow pathway depending on cerebral blood flow
      and intracranial pressure. The model explains the physiological strong coupling
      between intracranial pressure and venous pressure in the bridging veins, and we
      discuss the limits of applicability of the Starling resistor formula to the
      venous flow rates. The model provides a complementary explanation for ventricular
      collapse and origin of subdural hematomas resulting from overshunting in
      hydrocephalus. The noncontinuous pressure flow characteristic of the venous
      outflow is pinpointed as a possible source of the spontaneous generation of
      intracranial slow waves. CONCLUSION: A new conceptual mathematical model can be
      used to explain the relationship between pressures and flow at the venous outflow
      from the cranium.

PMID- 11846916
TI  - Pattern of cerebral aneurysms in Morocco: review of the concept of their rarity
      in developing countries: report of 200 cases.
AB  - OBJECTIVE: Many neurosurgeons consider cerebral aneurysms to be rare in Africa
      and the Middle East. In this report, we describe the pattern of cerebral
      aneurysms in Morocco and call into question the idea of their rarity in
      developing countries. Our objective is to urge neurosurgeons in these areas to
      track them and to treat them under better conditions. METHODS: We report a
      retrospective study of 200 patients with cerebral aneurysms admitted to our
      department between 1983 and 1999. The results of this study are supported by
      pertinent epidemiological surveys, anatomic studies on the incidence of cerebral
      aneurysms in Morocco, and analysis of the literature related to the epidemiology
      of aneurysms in developing countries. RESULTS: The patients in our series ranged
      in age from 7 to 70 years (mean age, 52 yr), with a slight female predominance
      (52%). They presented with subarachnoid hemorrhage (173 patients), cranial nerve
      palsy (18 patients), or mass symptoms (9 patients). The delay between
      subarachnoid hemorrhage and admission ranged from 1 to 30 days (mean, 14 d). The
      aneurysm was located in the internal carotid artery in 42%, in the anterior
      communicating and anterior cerebral arteries in 28%, in the middle cerebral
      artery in 19%, and in the vertebrobasilar artery in 10%. Multiple aneurysms were
      encountered in 9% and giant aneurysms in 15.5%. Seventeen patients died before
      surgery (with vasospasm in 13 cases and rebleeding in 4 cases), and 19 died after
      surgery. Follow-up, ranging between 1 and 10 years, revealed good outcomes with
      complete recovery in 64.5% and recovery with major sequelae in 7%. Pre- and
      postoperative mortality represented 18%; there was no operative treatment and no
      follow-up in 11.5%. CONCLUSION: Some data in this study (the delay between
      subarachnoid hemorrhage and admission, the high incidence of urban patients
      [80%], and the high rate of giant aneurysms) explain why many cases of ruptured
      aneurysms are not diagnosed. The analysis of our clinical series and the results
      of the epidemiological surveys show that the incidence has doubled every 5 years.
      These findings confirm that cerebral aneurysms are not rare in Morocco. A
      critical reading of the published articles claiming a low incidence of cerebral
      aneurysms in Africa, the Middle East, and Asia shows that this conclusion is not
      based on accurate and reliable statistical studies. Neurosurgeons in these
      regions should abandon this idea of rarity, and they should search for arterial
      cerebral aneurysms and develop the optimum conditions for the treatment of
      patients with aneurysms.

PMID- 11846917
TI  - The contributions of Otfrid Foerster (1873-1941) to neurology and neurosurgery.
AB  - BEST REMEMBERED FOR his description of the dermatomes in man, Otfrid Foerster was
      also an adept neurosurgeon and an innovative experimental neurophysiologist. As a
      neurologist, his contributions included conceptualizing rhizotomy as a cure for
      spasticity, anterolateral cordotomy for pain, the hyperventilation test in
      epilepsy, Foerster's syndrome, and the first electrocorticogram of a brain tumor.
      As a neurosurgeon, Foerster was able to excise intraventricular, hypophyseal, and
      quadrigeminal lesions and to perform epilepsy surgery under primitive conditions
      without clips, diathermy, or suction. The results were good and reflected his
      consummate knowledge of neuroanatomy and neurophysiology. As an investigator,
      Foerster emphasized clinically orientated neurophysiology and was able to forge a
      link between his observations and proposed methods of treatment. A prolific
      writer, he published more than 300 scientific monographs encompassing every
      aspect of the nervous system, including tabes, movement disorders, spasticity,
      extrapyramidal diseases, dermatomes, epilepsy, cortical localization, brain
      tumors, peripheral nerve injuries, and pain. Foerster's superb command of
      languages led to his popularity as a speaker in Europe and North America.
      Students who flocked to learn from his encyclopedic knowledge and skill were
      privy to Foerster's legendary hospitality and charm. A man of delicate
      constitution, he was single-minded in his quest to unravel the mysteries of the
      nervous system. The inscription "Patriae scientiae inserviendo" or "In the
      service of science and Fatherland" was chosen by Foerster for his Institute of
      Neurology and is a fitting memorial to this neurosurgical giant.

PMID- 11846918
TI  - Reversible posterior leukoencephalopathy occurring during resection of a
      posterior fossa tumor: case report and review of the literature.
AB  - OBJECTIVE AND IMPORTANCE: Our goal was to present a clinically and
      radiographically documented case of reversible posterior leukoencephalopathy
      (RPL) that occurred during resection of a posterior fossa tumor. Although RPL has
      been previously described in multiple nonsurgical settings, we hope that this
      case description makes RPL more clinically and radiographically recognizable to
      neurosurgeons. CLINICAL PRESENTATION: RPL is the clinical syndrome of headaches,
      altered mental status, seizures, and visual loss, with radiographic findings of
      reversible parieto-occipital changes on cerebral computed tomographic and
      magnetic resonance imaging scans. It has been previously reported in the settings
      of malignant hypertension, renal disease, eclampsia, and immunosuppression. To
      our knowledge, the patient presented represents the first clinically and
      radiographically documented case of RPL occurring during resection of a posterior
      fossa tumor. The patient intraoperatively exhibited wide fluctuations in blood
      pressure and awoke with clinical and radiographic findings consistent with RPL.
      INTERVENTION: Aggressive intraoperative and postoperative management of the
      patient's blood pressure, supportive intensive care, rehabilitation, and close
      radiographic follow-up were performed. CONCLUSION: RPL can occur as a result of
      intraoperative variations in blood pressure, even among young, previously healthy
      individuals. With the aforementioned interventions, the patient experienced
      significant clinical and radiographic recovery.

PMID- 11846919
TI  - Solitary fibrous tumor of the orbit with extraorbital extension: case report.
AB  - OBJECTIVE AND IMPORTANCE: Solitary fibrous tumors (SFTs) are rare tumors of
      mesenchymal origin that typically arise in the pleura. Only 24 cases of SFTs in
      the orbit have been reported, all located within the orbit and generally with a
      benign course. We report the first case of an orbital SFT with extraorbital
      extension and short-term regrowth. CLINICAL PRESENTATION: A 54-year-old man
      presented with proptosis and double vision that had persisted for 7 months. The
      tumor extended from the right extraconal inferolateral orbit to the extradural
      middle cranial fossa and cavernous sinus, via the superior orbital fissure, on
      magnetic resonance imaging scans. Positron emission tomography with
      [(18)F]fluorodeoxyglucose demonstrated faint uptake in the orbital portion.
      INTERVENTION: Resection of the tumor was performed twice, because of short-term
      regrowth of the residual tumor in the orbit. The histological diagnosis was a
      SFT. The MIB-1 labeling index was 7% and the mitotic count was 5 mitotic
      figures/10 high-power fields at the time of the second operation. These findings
      indicate the malignant nature of the tumor. CONCLUSION: The natural history of
      SFTs of the orbit remains unclear, and the importance of careful and continued
      follow-up monitoring of the tumor should be emphasized.

PMID- 11846920
TI  - The juxtaposition of a capillary telangiectasia, cavernous malformation, and
      developmental venous anomaly in the brainstem of a single patient: case report.
AB  - OBJECTIVE AND IMPORTANCE: Capillary telangiectasias, cavernous malformations, and
      developmental venous anomalies are all vascular malformations that occur on the
      capillary-venous side of the cerebral circulation. The associations of capillary
      telangiectasias with venous malformations, cavernous malformations with venous
      malformations, and capillary telangiectasias with cavernous malformations have
      all been described; however, the association of all three lesions in a single
      patient is extremely rare. CLINICAL PRESENTATION: A 52 year-old Caucasian woman
      presented to our clinic with an extended history of confusion, distorted visual
      perceptions, photophobia, neck pain, swallowing problems, and poor balance. The
      patient's examination was remarkable for difficulty concentrating, mild rotatory
      nystagmus, subtle decreased sensation over the left side of the face and body,
      and brisk reflexes. Review of the patient's magnetic resonance imaging
      examination demonstrated a cavernous malformation, a capillary telangiectasia,
      and a developmental venous anomaly located adjacent to one another in the
      brainstem. INTERVENTION: Given the patient's complex constellation of symptoms
      and relatively mild neurological findings, it was difficult to ascribe any one of
      them to a specific vascular malformation. Conservative management of this
      patient's vascular malformations was decided upon. CONCLUSION: Juxtaposition of
      these three different vascular lesions in the brainstem of an otherwise normal
      individual suggests a relationship among them. Although there are several
      theories that link similar associations through physiological mechanisms such as
      venous hypertension, we propose that a developmental event disrupting local
      capillary-venous pattern formation is a plausible alternative.

PMID- 11846921
TI  - Unilateral fixed dilation of the pupil as a false-localizing sign with
      intracranial hemorrhage: case report and literature review.
AB  - OBJECTIVE AND IMPORTANCE: Although other focal signs may prove "false
      localizing," it is a neurosurgical axiom that unilateral fixed dilation of the
      pupil occurs ipsilateral to a supratentorial mass. CLINICAL PRESENTATION: A 25
      year-old man collapsed with a dense right hemiplegia and a Glasgow Coma Scale
      score of 6 (eye opening, 1; motor, 4; verbal, 1) after rupture of a left middle
      cerebral artery aneurysm associated with an intrasylvian hematoma. Initially,
      both pupils had remained equal-sized and reactive: however, within hours, the
      right (contralateral) pupil became fixed and dilated (i.e., false localizing).
      For some time, the left (ipsilateral) pupil remained small and reactive; at
      emergency craniotomy, this also became fixed and equally dilated. INTERVENTION:
      After evacuation of the clot and wrapping of the aneurysm, both pupils rapidly
      became equal-sized and reactive. Twenty-four hours later, concurrent with massive
      left hemispheric swelling and a midline shift, the left (ipsilateral) pupil
      became unilaterally fixed and dilated (i.e., false localizing). Eventually, the
      right (contralateral) pupil also became fixed and dilated, concurrent with
      cardiovascular collapse. Death occurred within 10 hours. CONCLUSION: Unilateral
      fixed dilation of the pupil in patients with hemispheric mass lesions may be
      false localizing. Furthermore, disparate "herniating mechanisms" can arise
      despite mass effect emanating from the same side. Because such mechanisms cannot
      be witnessed, their nature remains speculative. An extensive review is contained
      in this article.

PMID- 11846922
TI  - Successful embolization of a spinal perimedullary arteriovenous fistula with
      cellulose acetate polymer solution: technical case report.
AB  - OBJECTIVE AND IMPORTANCE: Spinal perimedullary arteriovenous fistulae are rarely
      reported in the literature and can be treated via both endovascular and direct
      surgical approaches. Coils, glues, and balloons have all been used to embolize
      these fistulae. Cellulose acetate polymer (CAP) solution is a liquid embolic
      material that was originally developed for thrombosis of cerebral aneurysms. This
      is the first report of CAP solution being used to treat a spinal perimedullary
      arteriovenous fistula, with changes in the viscosity of the solution. CLINICAL
      PRESENTATION: A 15-year-old boy experienced spinal subarachnoid hemorrhage
      without any neurological deficits. A radiological examination revealed a spinal
      perimedullary arteriovenous fistula (Type 2) at the L1 level. INTERVENTION:
      Transarterial embolization was performed with local anesthesia. The microcatheter
      was navigated through the anterior spinal artery to a site just proximal to the
      fistula. After provocative testing demonstrated negative results, CAP solution
      was injected and the fistula was completely closed, without complications. The
      patient experienced an uneventful postoperative course. CONCLUSION: We describe
      the usefulness of CAP solution in the treatment of a spinal perimedullary
      arteriovenous fistula. This procedure must be performed for a larger series of
      patients for assessment of its long-term results.

PMID- 11846923
TI  - Percutaneous carotid angioplasty and stenting with the use of gadolinium in lieu
      of iodinated contrast medium: technical case report and review of the literature.
AB  - OBJECTIVE AND IMPORTANCE: We describe a patient who underwent percutaneous
      transluminal carotid angioplasty and stent placement with the use of intra
      arterial gadolinium (Gd-DTPA) instead of iodinated contrast medium. This
      represents one of the first published reports of the use of Gd-DTPA as an
      angiographic contrast agent for an interventional neuroradiological procedure.
      CLINICAL PRESENTATION: A 75-year-old man with renal insufficiency and multiple
      comorbidities developed amaurosis fugax. Doppler examination revealed high-grade
      stenosis of the right internal carotid artery. INTERVENTION: The patient
      underwent percutaneous transluminal balloon angioplasty with endovascular stent
      placement for 95% narrowing of the proximal right internal carotid artery.
      Because of his impaired renal function, the procedure was performed with the use
      of Gd-DTPA as the sole contrast agent. Approximately 60 ml of contrast medium
      (twice the volume typically used for a magnetic resonance imaging study) was
      used. There were no neurological, renal, or other complications. CONCLUSION:
      Intra-arterially administered Gd-DTPA may be substituted for iodinated contrast
      agents in complex neuroendovascular procedures. This capacity expands the
      armamentarium for interventional neuroradiological procedures.

PMID- 11846924
TI  - Peritoneography in the assessment of peritoneal cerebrospinal fluid absorption
      potential for distal ventriculoperitoneal shunt catheter placement: technical
      case report.
AB  - OBJECTIVE AND IMPORTANCE: Distal ventriculoperitoneal shunt failure has been
      associated with absorption failure secondary to previous peritonitis. This
      assumption has caused surgeons to seek alternate sites for distal catheter
      placement. We propose that the absorptive potential of the peritoneal cavity
      should be assessed before that site is discounted for catheter placement.
      CLINICAL PRESENTATION: The case of a 14-month-old male patient is presented,
      demonstrating multiple ventriculoperitoneal shunt placement procedures and a
      diagnostic dilemma with respect to distal shunt placement. Peritoneography was
      performed to demonstrate peritoneal fluid absorption, allowing subsequent
      placement of a new distal shunt catheter with good clinical results. TECHNIQUE:
      Using aseptic technique, a 24-gauge spinal needle was inserted in the midline of
      the abdomen and water-soluble contrast material was instilled. Delayed
      radiographs delineated peritoneal adhesions and demonstrated renal excretion of
      the contrast material, confirming peritoneal absorption. CONCLUSION: The
      peritoneal cavity remains the site of choice for distal shunt catheter placement.
      If failure of peritoneal cerebrospinal fluid absorption is suspected as a cause
      of shunt failure, then peritoneography with water-soluble contrast material may
      be safely used to demonstrate the adequacy of fluid absorption before a secondary
      site is chosen.

PMID- 11846925
TI  - Topography of the vestibulocochlear nerve.

PMID- 11846926
TI  - Intralesional resection of primary and metastatic sarcoma involving the spine:
      outcome analysis of 59 patients.
AB  - OBJECTIVE: Surgery plays an important role in achieving local tumor control and
      cure for primary and metastatic tumors of the spine. As has been established with
      regard to sarcomas at extraspinal sites, these goals may best be achieved by en
      bloc resection with negative histological margins. Unfortunately, sarcomas of the
      spine often present with tumor patterns that are amenable only to intralesional
      resection, if neurological preservation is a priority. This study is a
      retrospective analysis of the long-term outcomes of patients who had operations
      for sarcomas of the spine using modern surgical approaches, intralesional
      resections, and spinal instrumentation. METHODS: Between 1985 and 1997, 59
      patients had spinal operations for sarcoma involving the extrasacral spine. Data
      regarding tumor histology, grade, surgical indications, patterns of spinal tumor
      involvement, and neurological and functional outcomes were reviewed at
      presentation and at tumor recurrence. RESULTS: Thirty-five patients underwent a
      single operation, and 24 patients required reoperation for locally recurrent
      tumors. At presentation, only nine patients (15%) had tumors that were amenable
      to marginal or wide resections. Functional outcomes after initial spinal surgery
      and after operations performed at first tumor recurrence showed that 95% of
      patients had maintained or regained ambulation. Intradural extension of tumor was
      seen in 5 of 12 patients who had three or more operations for locally recurrent
      disease. The median survival from first spine operation was 18 months, and the
      median event-free interval between the first and second spine operations was 13
      months. CONCLUSION: Surgery for sarcoma of the spine is useful for maintaining or
      improving neurological and functional outcomes, but local tumor recurrences are
      common. Because of the anatomy of the tumor at presentation and concern for
      neurological preservation, few patients are candidates for marginal or wide
      resections.

PMID- 11846927
TI  - Age and radiation response in glioblastoma multiforme.
AB  - OBJECTIVE: Advanced age is a strong predictor of shorter survival in patients
      with glioblastoma multiforme (GM), especially for those who receive multimodality
      treatment. Radiographically assessed tumor response to external beam radiation
      therapy is an important prognostic factor in GM. We hypothesized that older GM
      patients might have more radioresistant tumors. METHODS: We studied
      radiographically assessed response to external beam radiation treatment (five
      level scale) in relation to age and other prognostic factors in a cohort of 301
      GM patients treated on two prospective clinical protocols. A total of 223
      patients (74%) were assessable for radiographically assessed radiation response.
      A proportional odds ordinal regression model was used for univariate and
      multivariate analysis. RESULTS: Younger age (P = 0.006), higher Karnofsky
      Performance Scale score before radiotherapy (P = 0.027), and more extensive
      surgical resection (P = 0.028) predicted better radiation response in univariate
      analyses. Results were similar when clinical criteria were used to classify an
      additional 61 patients without radiographically assessed radiation response
      (stable versus progressive disease). In multivariate analyses, age and extent of
      resection were significant independent predictors of radiation response (P <
      0.05); Karnofsky Performance Scale score was of borderline significance (P =
      0.07). CONCLUSION: Older GM patients are less likely to have good responses to
      postoperative external beam radiation therapy. Karnofsky Performance Scale score
      before radiation treatment and extent of surgical resection are additional
      predictors of radiographically assessed radiation response in GM.

PMID- 11846928
TI  - Reduced-dose radiosurgery for vestibular schwannomas.
AB  - OBJECTIVE: To evaluate tumor control and complications associated with low-dose
      radiosurgery for vestibular schwannomas. METHODS: Between December 1993 and
      January 2000, 47 patients with vestibular schwannomas were treated at our center
      with gamma knife radiosurgery. The marginal tumor doses ranged from 7.5 to 14.0
      Gy (median, 12.0 Gy) for patients treated after microsurgery and from 10.0 to
      15.0 Gy (median, 12.0 Gy) for patients in whom radiosurgery was the primary
      treatment. The median maximum tumor diameter was 18 mm (range, 3-50 mm).
      Evaluation included audiometry, neurological examination, and serial imaging
      tests. A survey was conducted at the time of analysis. RESULTS: Follow-up data
      were available for 45 patients and ranged from 1 to 7 years (median, 3.6 yr). In
      43 patients (96%), tumor control (no radiographic progression or surgical
      resection) was observed. All 33 previously untreated patients had tumor control.
      Transient facial weakness, experienced in two patients (4%), had resolved
      completely within 6 months. No patient developed trigeminal neuropathy. Hearing
      was diminished from baseline in 12% of patients with useful hearing (Gardner
      Robertson Class III). However, all patients with pretreatment hearing Gardner
      Robertson Class I or II maintained testable hearing (Class I to III) at the most
      recent examination. CONCLUSION: Low-dose radiosurgery in this series provided
      comparable local control and decreased incidences of complications in relation to
      other reports. Additional follow-up will allow more definitive conclusions to be
      reached regarding the ultimate rates of tumor control and hearing preservation.
      Nevertheless, the current dose used for vestibular schwannomas at the University
      of Maryland Medical Center is 12.0 Gy to the tumor periphery.

PMID- 11846930
TI  - Functional activity within brain tumors: a magnetic source imaging study.
AB  - OBJECTIVE: To determine whether low-grade gliomas contain functional cortical
      activity more often than high-grade gliomas within radiologically defined
      abnormal tissue. METHODS: Patients with intra-axial cerebral lesions located in
      the vicinity of eloquent brain cortex preoperatively underwent magnetic source
      imaging. A dual 37-channel biomagnetometer was used to perform the imaging.
      Evoked magnetic fields were analyzed using the single-equivalent dipole
      representation to ascertain the neuronal source. Stimuli included painless
      tactile somatosensory stimulation of fingers, toes, and lips and auditory
      presentation of pure sinusoidal tones. RESULTS: A retrospective analysis of 106
      nonconsecutively treated patients, who had undergone preoperative magnetic source
      imaging between February 1996 and December 1999, revealed that 24.5% of the
      patients had been at risk for neurological deficits, because functionally active
      tissue was located within or at the border of the tumor. Functional activity was
      found within the radiologically defined lesion in 18% of Grade 2 tumors, in 17%
      of Grade 3 tumors, and in 8% of Grade 4 tumors. CONCLUSION: The results confirm
      that, regardless of tumor grade, intra-axial brain tumors may involve or directly
      border on functional cortex. The degree of involvement of functionally viable
      cortex appeared greater for low-grade tumors than for high-grade lesions. On the
      other hand, high-grade lesions were more likely to be associated with functional
      cortex at their margins or within peritumoral edema. To safely maximize tumor
      resection, preoperative functional imaging and intraoperative
      electrophysiological mapping of the cerebral cortex and the white matter tracts
      are deemed necessary.

PMID- 11846929
TI  - Delayed cerebrovascular complications of intrathecal colloidal gold.
AB  - OBJECTIVE: Therapy with intrathecal colloidal gold has been used in the past as
      an adjunct in the treatment of childhood neoplasms, including medulloblastoma and
      leukemia. We describe the long-term follow-up period of a series of patients
      treated with intrathecal colloidal gold and emphasize the high incidence of
      delayed cerebrovascular complications and their management. METHODS: Between 1967
      and 1970, 14 children with posterior fossa medulloblastoma underwent treatment at
      the University of Minnesota. Treatment consisted of surgical resection, external
      beam radiotherapy, and intrathecal colloidal gold. All patients underwent long
      term follow-up periods. RESULTS: Of the 14 original patients, 6 died within 2
      years of treatment; all experienced persistent or recurrent disease. The eight
      surviving patients developed significant neurovascular complications 5 to 20
      years after treatment. Three patients died as a result of aneurysmal subarachnoid
      hemorrhage, and five developed ischemic symptoms from severe vasculopathy that
      resembled moyamoya disease. CONCLUSION: Although therapy with colloidal gold
      resulted in long-term survival in a number of cases of childhood medulloblastoma,
      our experience suggests that the severe cerebrovascular side effects fail to
      justify its use. The unique complications associated with colloidal gold therapy,
      as well as the management of these complications, are presented. We recommend
      routine screening of any long-term survivors to exclude the presence of an
      intracranial aneurysm and to document the possibility of moyamoya syndrome.

PMID- 11846931
TI  - A review of size and location of ruptured intracranial aneurysms.
AB  - OBJECTIVE: To review our experience and examine the size at which aneurysms
      ruptured in our patient population. METHODS: Patient charts and angiograms for
      all patients admitted with a diagnosis of subarachnoid hemorrhage to the Thomas
      Jefferson/Wills Eye Hospital between April 1996 and March 2000 were reviewed.
      RESULTS: Of the 362 cases reviewed, definite measurements of the ruptured
      aneurysm were obtained in 245. The data clearly showed that most ruptured
      aneurysms presenting to our institution were less than 10 mm in diameter. We
      found that, regardless of location on the circle of Willis, 85.6% of all
      aneurysms presenting with rupture were less than 10 mm. Review by location shows
      that aneurysms of the anterior communicating artery most often presented with
      rupture at sizes less than 10 mm (94.4%). A large number of ruptured posterior
      communicating artery aneurysms also presented at sizes less than 10 mm (87.5%).
      This trend continued for all aneurysm sites in our review. The incidence of
      subarachnoid hemorrhage in Western countries is estimated at 10 per 100,000
      people per year. Recent reports have indicated that aneurysms less than 10 mm in
      size are unlikely to rupture. CONCLUSION: We argue that the risk of small
      aneurysms rupturing is not insignificant, especially those of the anterior
      communicating artery. Our findings indicate that surgery on unruptured aneurysms
      should not be predicated on aneurysm size alone.

PMID- 11846933
TI  - Asymptomatic versus symptomatic infarcts from vasospasm in patients with
      subarachnoid hemorrhage: serial magnetic resonance imaging.
AB  - OBJECTIVE: By use of serial magnetic resonance imaging (MRI), we prospectively
      investigated the incidence of and the risk factors associated with infarction
      caused by vasospasm with or without a delayed ischemic neurological deficit
      (DIND) in patients with subarachnoid hemorrhage (SAH). METHODS: In 125 patients
      who underwent surgery for early aneurysms, postoperative MRI scans were obtained
      at four time points. We defined an infarct from vasospasm as a new lesion not
      present on the initial MRI within 3 days after SAH and therefore not attributable
      to primary brain damage or surgical complications. RESULTS: Overall, symptoms of
      infarction (i.e., DIND) occurred in 38% of patients (48 of 125); DIND with a new
      infarct on MRI was evident in 34% (43 patients), whereas 4% (5 patients) showed
      no new lesion but had a DIND. However, 29 patients (23%) showed a new infarct but
      no DIND on MRI studies (asymptomatic infarction). Asymptomatic ischemic lesions
      due to vasospasm tended to involve noneloquent brain areas in the territory of
      intraparenchymal perforators. Multivariate analysis identified variables
      associated with symptomatic infarction to be of poor SAH grade, advanced age of
      the patient, angiographic findings of vasospasm, multiple cortical infarcts on
      MRI studies consistent with vasospasm, and chronic hydrocephalus. CONCLUSION:
      Analysis of the data confirmed the occurrence of asymptomatic infarcts due to
      vasospasm. These infarcts often developed in noneloquent areas representing
      perforator territory. MRI investigation of vasospastic lesions referable to
      intraparenchymal vessels such as perforators complements the study of
      extraparenchymal major vessel vasospasm in patients with SAH by computed
      tomographic angiography.

PMID- 11846932
TI  - Remote cerebellar hemorrhage after supratentorial surgery.
AB  - OBJECTIVE: Remote cerebellar hemorrhage (RCH) is an infrequent and poorly
      understood complication of supratentorial neurosurgical procedures. We
      retrospectively compared 42 patients who experienced RCH with a case-matched
      control cohort, to delineate risk factors associated with the occurrence of this
      complication. METHODS: Between 1988 and 2000, 42 patients experienced RCH after
      supratentorial neurosurgical procedures at our institution. Diagnoses were made
      on the basis of postoperative computed tomographic or magnetic resonance imaging
      findings in all cases. The medical records for these patients were reviewed and
      compared with those for a control cohort of 43 patients, matched for age, sex,
      surgical lesion, and type of craniotomy, who were treated during the same period.
      RESULTS: RCH most commonly occurred after frontotemporal craniotomies for
      unruptured aneurysm repair or temporal lobectomy and was frequently an incidental
      finding on postoperative computed tomographic scans. However, some cases of RCH
      were associated with significant morbidity, and two patients died. Preoperative
      aspirin use and elevated intraoperative systolic blood pressure were
      significantly associated with RCH (P = 0.026 and P = 0.036, respectively).
      Pathological findings for two cases demonstrated hemorrhagic infarctions in both.
      CONCLUSION: RCH most commonly follows supratentorial neurosurgical procedures,
      performed with the patient in the supine position, that involve opening of
      cerebrospinal fluid cisterns or the ventricular system (such as unruptured
      aneurysm repair or temporal lobectomy). Preoperative aspirin use and moderately
      elevated intraoperative systolic blood pressure are potentially modifiable risk
      factors associated with the development of RCH. Although RCH can cause death or
      major morbidity, most cases are asymptomatic or exhibit a benign course.
      Cerebellar "sag" as a result of cerebrospinal fluid hypovolemia, causing
      transient occlusion of superior bridging veins within the posterior fossa and
      consequent hemorrhagic venous infarction, is the most likely pathophysiological
      cause of RCH.

PMID- 11846934
TI  - Surgical and endovascular flow disconnection of intracranial pial single-channel
      arteriovenous fistulae.
AB  - INTRODUCTION: Intracranial pial single-channel arteriovenous (AV) fistulae are
      rare vascular lesions of the brain. They differ from AV malformations in that
      they lack a true "nidus" and are composed of one or more direct arterial
      connections to a single venous channel. They often are associated with a venous
      varix because of their high-flow nature. The pathological aspects of pial AV
      fistulae arise from their high-flow dynamics; therefore, we think that
      disconnection of the AV shunt is enough to obliterate the lesion, and that lesion
      resection is unnecessary. Flow disconnection can be accomplished via surgical or
      endovascular means. Certain lesions have angiogeometric configurations, however,
      that are unfavorable for endovascular treatment. We reviewed the experience in
      our combined neurosurgical and neuroendovascular unit in the treatment of
      patients with pial single-channel AV fistulae. METHODS: From 1991 to 1999, the
      combined neurovascular unit at the Massachusetts General Hospital treated nine
      consecutive patients with nontraumatic intracranial pial single-channel AV
      fistulae. Carotid-cavernous fistulae and vein of Galen malformations were
      excluded from this analysis. The combined neurovascular team planned the
      treatment strategy for each patient on the basis of the anatomic location and the
      angiogeometry of each lesion. We retrospectively reviewed the medical records,
      office charts, operative reports, endovascular reports, and x-rays for each
      patient. Radiographic outcome was assessed by use of posttreatment angiography.
      Clinical outcome was assessed by an independent nurse practitioner. RESULTS: A
      treatment strategy of flow disconnection was used in all nine patients and was
      accomplished surgically in six patients, endovascularly in two patients, and by
      combined techniques in one patient. All nine lesions were completely obliterated
      as demonstrated radiographically, including obliteration of the venous varices
      associated with three of the lesions. With a mean long-term clinical follow-up of
      3.2 years (range, 0.3-8.4 yr), four patients were neurologically excellent with
      no deficits, two patients had pretreatment neurological deficits that did not
      worsen after treatment, one patient had transient dysphonia and dysphagia
      postoperatively that resolved, one patient had mild weakness after treatment, and
      one patient had moderate homonymous hemianopia after treatment. CONCLUSION:
      Single-channel pial AV fistulae can be treated by a strategy of flow
      disconnection. Resection of the lesion is not necessary. Flow disconnection can
      be accomplished either surgically or endovascularly; however, certain
      angiogeometric configurations are more favorable for surgical treatment. An
      experienced combined neurosurgical and neuroendovascular team can carefully
      determine the most appropriate treatment modality on the basis of patient
      specific and angiospecific factors.

PMID- 11846935
TI  - Hemifacial spasm: intraoperative electromyographic monitoring as a guide for
      microvascular decompression.
AB  - OBJECTIVE: Microvascular decompression is the logical and well-accepted treatment
      of choice for hemifacial spasm (HFS). In experienced hands, good to excellent
      results can be obtained. However, sometimes the exact site of the vascular
      compression is unclear. The aim of this study was to analyze whether
      intraoperative monitoring by stimulated electromyography of the facial nerve may
      help to improve the results of vascular decompression for HFS. METHODS: In a
      series of 74 patients operated for HFS, the impact of intraoperative facial nerve
      monitoring on the surgical procedure was analyzed by use of the clinical and
      operative patient records. The role of this type of monitoring, with assessment
      of the so-called abnormal muscle response, was broken down into four categories:
      a guiding, a confirming, an indirect confirming, or an inconclusive role. The
      relationship between abnormal muscle response monitoring results and final
      surgical outcome was analyzed. RESULTS: The overall cure rate was 87.8%,
      including patients who had previously undergone unsuccessful operations.
      Complications were minor, and hearing impairment was found in 2.7% of patients. A
      guiding role of intraoperative monitoring was apparent in 33.8% of patients, and
      a confirming role was demonstrated in 52.7% of patients, which resulted in a
      positive contribution of approximately 87% for intraoperative facial monitoring
      in microvascular decompression for HFS. In patients defined as guiding cases, the
      cure rate was 92%. CONCLUSION: This study demonstrates the applicability and
      usefulness of intraoperative facial nerve monitoring in microvascular
      decompression operations for HFS.

PMID- 11846936
TI  - Suprasellar meningiomas.

PMID- 11846937
TI  - Management of spontaneous cerebellar hematomas: a prospective treatment protocol.
AB  - OBJECTIVE: To identify easily applicable guidelines for the surgical and
      conservative management of spontaneous cerebellar hematomas. METHODS: A treatment
      protocol was developed and prospectively applied for the management of 50
      consecutive cases of cerebellar hematomas. The appearance of the fourth
      ventricle, adjacent to the hematoma, on computed tomographic scans was divided
      into three grades (normal, compressed, or completely effaced). The degree of
      fourth ventricular compression was correlated with the size and volume of the
      hematoma and the presenting Glasgow Coma Scale (GCS) score. The hematoma was
      surgically evacuated for all patients with Grade III compression and for patients
      with Grade II compression when the GCS score deteriorated in the absence of
      untreated hydrocephalus. Patients with Grade I or II compression were initially
      treated with only ventricular drainage in the presence of hydrocephalus and
      clinical deterioration. RESULTS: The degree of fourth ventricular compression was
      classified as Grade I in 6 cases, Grade II in 26, and Grade III in 18. The degree
      of fourth ventricular compression was significantly correlated with the volume of
      the hematoma (r(s) = 0.67, P < 0.0001), hydrocephalus (r(s) = 0.44, P = 0.001),
      the preoperative GCS score (r(s) = 0.43, P = 0.001), the maximal diameter of the
      hematoma (r(s) = 0.43, P = 0.001), and a midline location of the hematoma (chi(2)
      = 6.84, P < 0.009). Acute deterioration in GCS scores occurred for 6 (43%) of 14
      patients with Grade III ventricular compression who were conscious at
      presentation. Thirteen patients with Grade I or II ventricular compression and
      stable GCS scores of more than 13 were treated conservatively. Nine patients were
      treated with ventricular drainage only, and 28 underwent posterior fossa
      craniectomy and evacuation of the hematoma with ventricular drainage. The
      mortality rate at 3 months was 40%. None of the patients with Grade III fourth
      ventricular compression and GCS scores of less than 8 at the time of treatment
      experienced good outcomes. Overall, 15 (60%) of 25 patients with hematomas with
      maximal diameters of more than 3 cm and Grade I or II compression did not require
      clot evacuation. CONCLUSION: Conscious patients with Grade III fourth ventricular
      compression should undergo urgent clot evacuation before deterioration. Surgical
      evacuation of the clot may not be required for large hematomas (>3 cm) if the
      fourth ventricle is not totally obliterated at the level of the clot.

PMID- 11846938
TI  - Surgical pathology of spinal schwannomas: a light and electron microscopic
      analysis of tumor capsules.
AB  - OBJECTIVE: Although spinal schwannomas are often encountered, the pathology of
      the tumor capsule has not been reported. In this study, we describe the
      ultrastructural pathology of the tumor capsule of spinal schwannomas. METHODS: In
      18 patients who underwent total removal of spinal schwannomas (C2-conus), the
      tumor capsule was collected and examined by light and electron microscopy.
      RESULTS: The thickness of the tumor capsule ranged from 15 to 800 microm (mostly
      30-100 microm) and was composed of three layers from the surface to the center:
      1) a thinly stretched nerve tissue layer; 2) a fibrous layer of fibrocytes,
      abundant collagen fibers, and tumor vessels; and 3) a thin transitional layer
      intermingled with fibrous components and tumor cells. The thickness of each layer
      varied in different regions of the surface. There was no clear separation between
      the tumor capsule and the neoplastic tissue, even on the electron microscopic
      level. A number of nerve fibers ran through the fibrous layer and beneath the
      capsule as well as in the nerve tissue layer. CONCLUSION: Compared with
      vestibular schwannomas, which have been reported to be covered by an extremely
      thin layer (3-5 microm) of connective tissue, spinal schwannomas were well
      encapsulated. The capsule was composed of three distinct components; however, the
      cleavage between thin capsule and tumor cells was indistinct, and the thickness
      of the axon-containing capsule varied from site to site. Therefore, resection of
      the nerve of tumor origin, rather than enucleation, would be justified to avoid
      tumor recurrence. Surgeons should be aware of this pathology when performing the
      procedure.

PMID- 11846939
TI  - Inferior temporal sulcus as a site of corticotomy: magnetic resonance imaging
      analysis of individual sulcus patterns.
AB  - OBJECTIVE: Transcortical approaches to the inferior horn often result in quadrant
      hemianopsia attributable to the injury to the optic radiation. The inferior
      temporal sulcus (ITS) has received little attention as an entrance point for the
      transsulcal approach. We used the method of detecting the ITS with magnetic
      resonance imaging (MRI) scans and investigated the sulcus pattern of ITS, its
      incidence rate, and the availability of the ITS to the corticotomy for selective
      amygdalohippocampectomy. METHODS: The sulcus patterns of the ITS of 100 temporal
      lobes in 50 healthy individuals were classified according to the number of
      interruptions by gyral bridges, and the localization of the ITS was characterized
      in relation to the outer surface by means of the surface anatomy scan of MRI.
      RESULTS: Most of the ITS was interrupted by one to three gyral bridges (0
      bridges, 8%; one bridge, 27%: two bridges, 37%; three bridges, 20%; more than
      four bridges or no apparent ITS, 8%). When the ITS was present, it was located 15
      mm above the orbitotragus line at a point 20 mm anterior to the tragus. The
      number of gyral bridges was significantly larger in the left temporal lobes than
      in the right temporal lobes, regardless of the sex of the subject. CONCLUSION:
      The ITS was clearly identified in 72% of the temporal lobes by the oblique
      sagittal view of MRI scans; thus, in such cases, the ITS was considered to be a
      candidate for an entrance point of a small temporal corticotomy. The preoperative
      observation of the ITS in relation to the orbitotragus line by means of MRI may
      improve the planning of the transsulcal approaches to deeply seated mesial
      temporal lesions, such as hippocampal sclerosis.

PMID- 11846940
TI  - Immediate stiffness of the C5-C6 segment after discectomy with the Cloward
      technique: an in vitro biomechanical study on a human cadaveric model.
AB  - OBJECTIVE: To determine whether the Cloward technique of cervical discectomy and
      fusion increases immediate postoperative stiffness of single cervical motion
      segment after application of interbody dowel bone graft. METHODS: We measured and
      compared the stiffness of single-motion segments in cadaveric cervical spines
      before and immediately after interbody fusion with the Cloward technique. Changes
      in range of motion and stiffness of the C5-C6 segment were measured in a bending
      flexibility test (flexion, extension, lateral bending and axial rotation) before
      and after a Cloward procedure in 11 fresh-frozen human cadaveric specimens from
      the 4th through the 7th vertebrae. RESULTS: The Cloward procedure produced a
      statistically significant increase in stiffness of the operated segment in
      flexion and lateral bending when compared with the intact spine. The less stiff
      the segment before the operation, the greater the increase in its postoperative
      flexural stiffness (statistically significant). The Cloward procedure produced
      nonuniform changes in rotational and extensional stiffness that increased in some
      specimens and decreased in others. CONCLUSION: Our data demonstrate that Cloward
      interbody fusion increases immediate postoperative stiffness of an operated
      segment only in flexion and lateral bending in cadaveric specimens in an in vitro
      environment. Thus, Cloward fusion seems a relatively ineffective method for
      increasing the stiffness of a construct. This may add to discussion on the use of
      spinal instrumentation and postoperative management of patients after cervical
      discectomy, which varies from bracing in hard collars through immobilization in
      soft collars to no external orthosis.

PMID- 11846941
TI  - Comparison of frameless stereotactic systems: accuracy, precision, and
      applications.
AB  - OBJECTIVE: Frameless stereotactic systems have become an integral part of
      neurosurgical practice. At our center, we recently introduced for clinical use a
      small, portable, frameless stereotactic system, namely the Cygnus PFS system
      (Compass International, Rochester, MN). The purpose of this study was to compare
      the accuracy of the Cygnus PFS system with that of two larger systems that are
      also currently in use at our institution, i.e., the SMN system (Zeiss,
      Oberkochen, Germany) and the ISG viewing wand (ISG Technologies, Toronto,
      Canada). These systems represent three kinds of frameless stereotactic
      technologies that are commercially available. Each system uses a different method
      of spatial localization, i.e., mechanical linkage (ISG system), magnetic field
      digitization (Cygnus system), or optical technology (SMN system). METHODS: Using
      a stereotactic "phantom," we measured the accuracies of all three systems with
      identical data sets. The errors in localization in three-dimensional space for
      nine targets were calculated by using 10 magnetic resonance imaging data sets.
      The precision of each system was also calculated. RESULTS: With this experimental
      protocol, the Cygnus system attained a mean accuracy of 1.90 +/- 0.7 mm, the ISG
      viewing wand system a mean accuracy of 1.67 +/-0.43 mm, and the SMN microscope a
      mean accuracy of 2.61 +/- 0.99 mm. The precision values were not significantly
      different among the systems. CONCLUSION: We observed only small differences in
      accuracy and precision among these three systems. We briefly review the
      advantages and disadvantages of each system and note that other factors, such as
      portability, ease of use, and microscope integration, should influence the
      selection of a frameless stereotactic system.

PMID- 11846942
TI  - Discovering trepanation: the contribution of Paul Broca.
AB  - PAUL BROCA WAS an icon of neuroscience and neurosurgery who also happened to be
      intrigued by trepanned skulls. His anthropological work established that,
      thousands of years ago, individuals not only trepanned skulls but also
      successfully performed these operations on living persons. After first commenting
      on a pre-Columbian Peruvian skull in 1867 (the first case of trepanning on a
      living person widely recognized as such), he turned to even older trepanned
      skulls found on French soil. In the 1870s, he theorized that the procedure
      originated as a means to treat convulsions in infants. As he saw it, Neolithic
      man attributed such convulsions to evil spirits, for which trepanation provided a
      ready means of escape. Because simple infantile convulsions resolve on their own,
      the practice would have seemed successful, and therefore it would have been
      propagated and expanded by later generations. Broca's theory skillfully
      integrated his anthropological and medical knowledge and helped to create the
      exciting environment in which scientists pondered what Neolithic and primitive
      people really knew regarding the brain and surgery.

PMID- 11846943
TI  - Coadministration of methylprednisolone with hypertonic saline solution improves
      overall neurological function and survival rates in a chronic model of spinal
      cord injury.
AB  - OBJECTIVE: We previously demonstrated that administration of 7.5% hypertonic
      saline (HS) significantly improved spinal cord blood flow and neurological
      outcomes after spinal cord injury. The aim of this study was to determine whether
      hypertonicity would enhance the effects of methylprednisolone (MP), further
      improving neurological function. METHODS: Rat spinal cords were compressed for 10
      minutes with 50 g of weight, and neurological function was assessed for 28 days,
      using the Basso-Beattie-Bresnahan locomotor rating scale. The control group
      received an intravenous injection of isotonic saline (IS) (5 ml/kg). Group 1
      received an intravenous injection of 7.5% HS (5 ml/kg). Group 2 received an
      intravenous injection of MP (30 mg/kg) and IS (5 ml/kg). Group 3 received an
      intravenous injection of MP (30 mg/kg) administered with 7.5% HS (5 ml/kg).
      RESULTS: At 24 hours after spinal cord injury, the combination of MP plus HS
      provided significant (P < 0.01) neurological improvements, compared with all
      other treatment groups. At 10 days after injury, the animals that had received MP
      plus HS exhibited significantly (P < 0.01) higher Basso-Beattie-Bresnahan scores,
      compared with the MP plus IS and control groups. The median survival time was
      significantly (P < 0.01) increased for the MP plus HS group (28 d), compared with
      the MP plus IS group (16 d). Because of the dramatic decrease in survival rates
      at 28 days after injury, there was a significant (P < 0.01) difference in
      neurological function only between the MP plus HS group and the control group.
      CONCLUSION: The results indicate that the administration of HS may enhance the
      delivery of MP and prevent immunosuppression, leading to improvements in overall
      neurological function and survival rates after spinal cord injury.

PMID- 11846944
TI  - Effect of melatonin on cerebral edema in rats.
AB  - OBJECTIVE: Melatonin (5-methoxy-N-acetyltrypamine), a chemical naturally produced
      in the pineal gland, has been suggested to be a free radical scavenger and an
      antioxidant. In the present study, the effect of melatonin on cold-induced brain
      edema was evaluated by determination of cerebral water content, blood-brain
      barrier permeability, and areas of infarct; the effects were also studied
      histopathologically. METHODS: Brain edema was produced in rats by creating a
      lesion via cortical freezing. Animals were separated into four groups: sham
      operated (craniectomy only); control (cold injury); sham-vehicle (cold injury
      plus saline); and melatonin treatment (cold injury plus melatonin). Melatonin was
      administered (50 mg/kg intraperitoneally) 15 minutes after the cold injury was
      induced. Twenty-four hours later, tissue samples from the core, from the
      periphery of the cold-injured hemisphere, and from the contralateral hemisphere
      symmetrical to the cold injury were obtained. RESULTS: Melatonin treatment
      reduced edema (mean +/- standard deviation; 86.22 +/- 1.54% in the control group
      versus 80.78 +/- 2.76% in the melatonin treatment group, P < 0.001) and blood
      brain barrier permeability (45.34 +/- 2.75% in the control group versus 38.26 +/-
      3.40% in the melatonin treatment group, P < 0.001) at the periphery of cold
      injury. Area of infarct reduced from 5.84 +/- 0.58% in the control group to 3.30
      +/- 0.89% in the melatonin treatment group (P < 0.001). The effect of melatonin
      was also confirmed histopathologically. CONCLUSION: Melatonin was found to be
      neuroprotective in instances of cold-induced brain edema. Thus, melatonin may be
      a valuable therapeutic agent in the treatment of cerebral edema.

PMID- 11846945
TI  - Postischemic intravenous administration of magnesium sulfate inhibits hippocampal
      CA1 neuronal death after transient global ischemia in rats.
AB  - OBJECTIVE: We aimed to determine an effective dose schedule for intravenously
      administered magnesium, to establish its neuroprotective efficacy in both pre-
      and postischemic treatment paradigms, and to compare the neuroprotective
      properties of MgSO(4) and MgCl(2). METHODS: Rats that had been subjected to the
      bilateral carotid artery occlusion plus hypotension model of transient forebrain
      cerebral ischemia received either an intravenously administered loading dose (LD)
      of 360 micromol/kg MgSO(4) only or an intravenously administered LD of 360
      micromol/kg followed by a 48-hour intravenous infusion of MgSO(4) at either 60,
      120, 240, or 480 micromol/kg/h. For evaluation of the efficacy of MgSO(4) after
      ischemia, the dose (LD, 360 micromol/kg; infusion, 120 micromol/kg/h) that
      provided maximal neuroprotection before ischemia was administered 4, 8, 12, or 24
      hours after ischemia. MgCl(2) (LD, 360 micromol/kg; infusion, 120 micromol/kg/h)
      was administered before and 8 hours after ischemia. At 7 days after ischemia,
      hippocampal CA1 neurons were histologically examined for protection. RESULTS:
      Animals that received the LD only demonstrated 33% hippocampal CA1 neuronal
      survival. Animals that received the LD followed by continuous infusion of MgSO(4)
      at either 60, 120, 240, or 480 micromol/kg/h demonstrated 30, 80, 16, and less
      than 5% CA1 neuronal survival, respectively. MgSO(4) treatment commencing at 4,
      8, 12, or 24 hours resulted in 82, 71, 52, and 33% CA1 neuronal survival,
      respectively. Preischemic and 8-hour postischemic administration of MgCl(2)
      resulted in 50% and less than 5% CA1 neuronal survival, respectively. CONCLUSION:
      These results demonstrate a neuroprotective intravenous dose of MgSO(4), which is
      effective when administered before or late after ischemia, and a previously
      uncharacterized dose-response curve for MgSO(4).

PMID- 11846946
TI  - Cervical sympathetic schwannoma: case report.
AB  - OBJECTIVE AND IMPORTANCE: Approximately 20 to 27% of neck masses in the
      parapharyngeal space may be benign nerve sheath tumors. Cervical sympathetic
      chain schwannomas or vagal nerve schwannomas are most common. We report a patient
      with a cervical sympathetic chain schwannoma. CLINICAL PRESENTATION: The patient
      was a 47-year-old Caucasian man with a 7-month history of a painless, enlarging
      right neck mass. No hoarseness or Horner's syndrome was found preoperatively.
      Formal head and neck examination in the otolaryngology department revealed no
      vocal cord dysfunction. INTERVENTION: By use of a standard right carotid
      incision, a tumor was identified growing from the cervical sympathetic chain
      posterior to the carotid bifurcation. A gross total resection was performed and a
      section of the cervical sympathetic chain was sacrificed. CONCLUSION: Cervical
      sympathetic chain schwannomas are unusual tumors that require microneurosurgical
      resection for cure. We discuss the differential diagnosis, evaluation, surgical
      management, and pathological characteristics of such tumors and review the
      literature.

PMID- 11846947
TI  - Meralgia paresthetica occurring 40 years after iliac bone graft harvesting: case
      report.
AB  - OBJECTIVE AND IMPORTANCE: Meralgia paresthetica is an entrapment neuropathy
      involving the lateral femoral cutaneous nerve. We describe an unusual case in
      which meralgia paresthetica occurred many years after iliac bone graft
      harvesting. CLINICAL PRESENTATION: An 81-year-old man presented with a 1-year
      history of pain, dysesthesia, and hypesthesia in the anterolateral aspect of the
      right thigh. This patient had undergone iliac bone grafting when he sustained a
      calcaneal fracture 40 years previously. Radiographs and computed tomographic
      scans of the pelvis revealed a bony excrescence in the anterosuperior iliac
      spine. INTERVENTION: The patient underwent neurolysis of the lateral femoral
      cutaneous nerve and excision of the bony excrescence. At surgery, the nerve was
      densely adherent to the bony excrescence. CONCLUSION: The etiology of meralgia
      paresthetica in this patient is considered to be heterotopic ossification on the
      anterosuperior iliac spine and pubic symphysis degeneration. A significant
      relationship between pubic symphysis degeneration with increasing age and
      meralgia paresthetica has been reported. One should be aware of meralgia
      paresthetica as a late complication of iliac bone graft harvesting.

PMID- 11846948
TI  - Atypical pleomorphic astrocytoma in the pineal gland: case report.
AB  - OBJECTIVE AND IMPORTANCE: We report a rare case of pleomorphic astrocytoma in the
      pineal region that took a benign course despite pleomorphism. CLINICAL
      PRESENTATION: A 30-year-old woman suddenly developed right hemiparesis followed
      by loss of consciousness. A computed tomographic scan revealed a mass in the
      pineal region accompanied by obstructive hydrocephalus. Her symptoms improved
      after ventriculoperitoneal shunt surgery. INTERVENTION: The tumor was totally
      removed in an en bloc fashion using the occipital interhemispheric transtentorial
      route. Light microscopy revealed that the tumor had marked pleomorphism and
      multinucleated, bizarre giant cells, but neither mitosis nor necrosis was seen.
      Glial fibrillary acid protein was immunohistochemically positive in a few tumor
      cells. Retinal soluble antigen was negative. No reticulin network between the
      tumor cells was observed. A histological diagnosis of atypical pleomorphic
      astrocytoma was made. CONCLUSION: No signs of recurrence have been observed for 7
      years after surgery without adjuvant therapy. Histologically, the tumor resembled
      pleomorphic xanthoastrocytoma or pleomorphic granular cell astrocytoma, but the
      immunohistochemical findings were not completely compatible with either
      diagnosis. This benign astrocytoma in the pineal gland with unique features is
      the first such case reported.

PMID- 11846949
TI  - Pseudomyasthenia resulting from a posterior carotid artery wall aneurysm: a novel
      presentation: case report.
AB  - OBJECTIVE AND IMPORTANCE: Painful oculomotor palsy can result from enlargement or
      rupture of intracranial aneurysms. The IIIrd cranial nerve dysfunction in this
      setting, whether partial or complete, is usually fixed or progressive and is
      sometimes reversible with surgery. We report an unusual oculomotor manifestation
      of a posterior carotid artery wall aneurysm, which mimicked ocular myasthenia
      gravis. CLINICAL PRESENTATION: A 47-year-old woman developed painless,
      intermittent, partial IIIrd cranial nerve palsy. She presented with isolated
      episodic left-sided ptosis, which initially suggested a metabolic or
      neuromuscular disorder. However, digital subtraction angiography revealed a left
      posterior carotid artery wall aneurysm, just proximal to the origin of the
      posterior communicating artery. INTERVENTION: The aneurysm was successfully
      clipped via a pterional craniotomy. During surgery, the aneurysm was observed to
      be compressing the oculomotor nerve. The patient's symptoms resolved after the
      operation. CONCLUSION: The variability of incomplete IIIrd cranial nerve deficits
      can present a diagnostic challenge, and the approach for patients with isolated
      IIIrd cranial nerve palsies remains controversial. Although intracranial
      aneurysms compressing the oculomotor nerve classically produce fixed or
      progressive IIIrd cranial nerve palsies with pupillary involvement, anatomic
      variations may result in atypical presentations. With the exception of patients
      who present with pupil-sparing but otherwise complete IIIrd cranial nerve palsy,
      clinicians should always consider an intracranial aneurysm when confronted with
      even subtle dysfunction of the oculomotor nerve.

PMID- 11846951
TI  - Upaupa Schneklud, by Paul Gauguin (1848-1903).

PMID- 11846950
TI  - Paramedian supracerebellar transtentorial approach for a medial tentorial
      meningioma with supratentorial extension: technical case report.
AB  - OBJECTIVE AND IMPORTANCE: The choice of surgical approach to treat medial
      tentorial meningiomas is crucial and sometimes difficult to make. Although the
      subtemporal approach is most commonly used for lesions that extend mostly
      supratentorially, it risks injury to the vein of Labbe or the veins coursing
      along the subtemporal surface. To avoid venous injury, a medial tentorial
      meningioma was removed transtentorially through the infratentorial space via the
      paramedian supracerebellar transtentorial (PSCTT) approach. CLINICAL
      PRESENTATION: A 35-year-old right-handed woman presented with a generalized
      convulsion. Magnetic resonance imaging scans revealed a left medial tentorial
      meningioma with supratentorial extension at the dominant hemisphere. The main
      venous drainage route from the ipsilateral temporal lobe was a sphenopetrosal
      vein. INTERVENTION: An operation was performed with the patient in a sitting
      position, and the tumor was resected totally via the paramedian supracerebellar
      transtentorial approach without perioperative complications. CONCLUSION: The
      paramedian supracerebellar transtentorial approach is useful for supratentorially
      located medial tentorial meningiomas without retraction of the temporal lobe and
      without damage to the vein of Labbe or the sphenopetrosal vein.

PMID- 11846952
TI  - Gauguin, a man ever in revolt.

PMID- 11846953
TI  - Pallidotomy: a comparison of responders and nonresponders.

PMID- 11846954
TI  - Molecular identity and regulation of renal potassium channels.
AB  - K channels are ubiquitous in animal cells, where they are involved in a variety
      of physiological functions. In epithelial cells of the kidney, K channels are
      primarily involved in maintaining membrane potential, recycling and secreting K
      and regulating cell volume. As many renal K channels have now been studied or
      identified at the molecular level by means of a variety of approaches, including
      patch-clamp recordings, cDNA cloning and immunohistochemistry, the purpose of
      this review is to summarize what is presently known about the molecular identity
      of renal K channels with an emphasis on their regulatory properties.

PMID- 11846955
TI  - Is the cell a gel--and why does it matter?
AB  - That the cell is a gel is broadly acknowledged. Textbooks begin with this
      assertion-and then proceed with great abandon to derive mechanisms based on free
      diffusion, as though the gel concept were groundless and cell was an aqueous
      solution. This disconnect emerges in part because the behavior of gels is not
      well understood, particularly among most biologists. Recently, great strides have
      been made in the understanding of gel behavior. It has become clear, for example,
      that a central mechanism in gel function is the phase-transition-a qualitative
      structural change prompted by a subtle change of environment, not unlike the
      transition from ice to water. Phase-transitions are capable of doing work. If the
      cell is a gel, then a logical approach to understanding cell function is to
      understand gel function-especially whether some role may be played by the phase
      transition. Here we pursue this approach. We first consider the dichotomy of the
      cell as a gel and the cell as an aqueous solution. We then set up a gel-based
      foundation for cell behavior, in which the gels' physical chemical features are
      used to explore how the cell achieves its everyday tasks. If there is a common
      underlying mechanism of cell function, it appears that the polymer gel phase
      transition could well be a candidate.

PMID- 11846956
TI  - Sarcoplasmic reticulum Ca(2+) content affects 4-CmC and caffeine contractures of
      rat skinned skeletal muscle fibers.
AB  - This study investigated whether the sarcoplasmic reticulum Ca(2+) content of rat
      skeletal muscle fibers affected contractile responses obtained by an application
      of 4-chloro-m-cresol (4-CmC) and caffeine. Contractures were elicited on saponin
      skinned fibers under different Ca(2+) loading conditions. The amplitude of 4-CmC
      and caffeine contractures of fast-twitch muscle fibers (edl, extensor digitorum
      longus) differed between the different loading conditions, and this is associated
      with a greater change in sensitivity to 4-CmC. When the sarcoplasmic reticulum
      was loaded with a low Ca(2+) concentration for a short period, the 4-CmC
      concentration providing half-maximal response was tenfold higher than with a
      larger sarcoplasmic reticulum Ca(2+) loading for a longer period, whereas for
      caffeine this concentration was only twofold higher in the same conditions. These
      findings indicate that 4-CmC contractile responses of edl muscle fibers are more
      dependent on luminal Ca(2+) activity than those of caffeine are. Thus 4-CmC would
      appear to be of greater interest than caffeine for the study of muscle
      contractile responses where variations in intracellular Ca(2+) activity exist.

PMID- 11846957
TI  - An estimation of buffer values of human whole blood by titration experiment under
      the open condition for carbon dioxide gas.
AB  - We studied the buffer mechanism of human whole blood by means of a titration
      experiment under the open condition in which blood is exposed to carbon dioxide
      gas. Van Slyke proposed the theory of a blood buffer mechanism in 1922 (J Biol
      Chem 52: 525-570). However, his theory is not applicable to our experiments
      because it did not take into consideration the effects of changes in volume and
      the concentration of bicarbonate ion in the buffer as a result of titration. We
      studied the blood buffer mechanism theoretically by using graphical
      representation and developed a theory, which we then applied to our experiments.
      Buffer value, as defined by Van Slyke, is the quantity of the base deltan(OH)/V
      in the sample without volume change (in gram equivalent per liter) required to
      change one unit in pH. Based on our blood buffer theory, we obtain the
      experimental buffer value betaprime prime or minute, which is the reciprocal
      slope of the dpH-bdV/V (deltan(OH) in the sample with volume change) relation
      during a titration experiment at a constant carbon dioxide pressure (pCO(2)) with
      volume change dV and an isotonic NaOH concentration of b = 0.15 M. The true
      buffer value beta under physiological conditions is estimated to be beta =
      deltan(OH)/VdpH = betaprime prime or minute (0.15 minus sign [HCO(3)(minus
      sign)])/0.15. Here, [HCO(3)(minus sign)] is the concentration of bicarbonate ion
      in blood that can be calculated by using the Henderson-Hasselbalch equation. We
      determined the agreement of our experimental results with the theoretical results
      and estimated the quantity m(A) of the buffer component, except for the
      bicarbonate buffer, and the dissociation constant K(A) of the buffer reaction in
      a neutral pH range. The true buffer value of whole blood can be estimated by
      using our theory and the results of precise experiments.

PMID- 11846958
TI  - Identical unitary current amplitude and Ca(2+) block of cardiac Na channel before
      and during beta-adrenergic stimulation.
AB  - We examined the possibility of Ca(2+) permeation through cardiac Na channels
      ("slip mode conductance") by an analysis of the voltage-dependent block of Na
      channels by Ca(2+). A Ca(2+) block of Na channels was evident in rat and guinea
      pig ventricular myocytes during cell-attached single channel recordings with a
      physiological ionic environment (140 mM Na(+) and 1 to 10 mM Ca(2+) in the
      pipette solution). Increasing external Ca(2+) concentration ([Ca(2+)](o)) in the
      pipette solution reduced the unitary current amplitude predominantly at negative
      potentials. With [Ca(2+)](o) > 1 mM, unitary current amplitude did not increase
      at potentials negative to -40 mV in spite of augmented driving forces. The
      application of 5 microM isoproterenol potentiated the single channel activity
      elicited by depolarizing pulses from the holding potential of -120 mV, indicating
      that the channels in the patch under examination were modified by protein kinase
      A (PKA) stimulation. Increased activity was also confirmed with veratridine
      modified Na channels, where channel openings were markedly prolonged. In either
      case, isoproterenol-induced potentiation neither reduced nor altered the
      properties of Ca(2+) block of cardiac Na channels, as evidenced by the stable
      unitary current amplitudes at potential levels from -60 to -20 mV. These results
      indicate that interactions among Na(+), Ca(2+), and the channel molecule were not
      modified with respect to permeation properties. They therefore argue against the
      "slip mode" concept of classical cardiac Na channel if a general concept of ion
      permeation through "multi-ion pores" is applicable to determine the ionic
      selectivity of Na channels.

PMID- 11846959
TI  - Depressor and bradycardic actions of L-proline injected into the nucleus tractus
      solitarii of anesthetized rats.
AB  - L-Glutamate has been considered to be a neurotransmitter in the nucleus tractus
      solitarius (NTS) of the afferent baroreflex pathway, though this has not yet been
      decisively shown. A bolus injection of a neurotransmitter candidate amino acid L
      proline into the cisterna magna and that of L-glutamate shows the same pressor
      action in the freely moving rat, but the actual nuclei responding L-proline
      remain undetermined. Besides L-glutamate, L-proline might be another candidate
      amino acid in the NTS. The present study was therefore performed to characterize
      the circulatory action of L-proline injected into the NTS where responses to
      glutamate in the anesthetized rat had already been shown. The NTS was first
      determined as a site on the dorsal surface of the medulla where a microinjection
      of L-glutamate decreased arterial pressure and heart rate. Microinjected L
      proline (1.65 to 13.2 nmol, 33 nl) into the NTS decreased arterial pressure and
      heart rate in a dose-dependent manner. The injection of a mixed solution (66 nl)
      of kynurenate, an ionotropic excitatory amino acid receptors antagonist (1.32
      nmol), and L-proline (6.6 nmol) into the NTS abolished the depressor and
      bradycardic actions with L-proline alone (6.6 nmol, 66 nl). However, a mixture of
      an increased concentration of kynurenate (6.6 nmol) with glutamate augmented the
      actions seen with glutamate alone (0.66 nmol, 66 nl). D-Proline (13.2 nmol, 66
      nl), the optic isomer of L-proline, produced no change in arterial pressure or
      heart rate, suggesting that the actions of L-proline in the NTS were optically
      specific. The results indicate that L-proline but not D-proline induces its
      depressor and bradycardic actions through ionotropic excitatory amino acid
      receptors in the NTS of the anesthetized rat. L-Proline may become a candidate
      transmitter of baroreceptor information in the NTS.

PMID- 11846960
TI  - Nitric oxide inhibits smooth muscle responses evoked by cholinergic nerve
      stimulation in the guinea pig gastric fundus.
AB  - In circular smooth muscle tissues of the guinea pig gastric fundus, transmural
      nerve stimulation (TNS) evoked an atropine-sensitive cholinergic excitatory
      junction potential (e.j.p.) and, after inhibiting the e.j.p. with atropine, an
      apamin-sensitive nonadrenergic noncholinergic (NANC) inhibitory junction
      potential (i.j.p.). The amplitude of e.j.p.s was similar when the frequency of
      TNS was low (<0.5 Hz), but it decreased successively (depression phenomenon) when
      the frequency was high (>1 Hz). The depression phenomenon was attenuated after
      inhibiting the production of nitric oxide (NO) with N(omega)-nitro-L-arginine
      (NOLA), but was not altered by inhibiting the i.j.p. with apamin. The e.j.p.s
      were increased in amplitude by the inhibition of cholinesterase activity, but
      they were decreased by NO produced from SNP with no alteration of their
      depression phenomenon. Isometric twitch contractions were depressed during high
      frequency TNS. NOLA caused an increase in the amplitude of twitch contractions
      and the attenuation of their depression that changed the transient contraction
      produced by high-frequency TNS (1 Hz) to a tetanic one. SNP reduced the amplitude
      of twitch contractions, with no alteration of the depression phenomena.
      Contractions produced by low concentrations of acetylcholine, but not by high
      concentrations, were attenuated by SNP, with no alteration of the membrane
      depolarization. The results suggest that NO produced during TNS has inhibitory
      actions on cholinergic transmission; the depression of e.j.p.s is mainly
      prejunctional events, and the depression of mechanical responses is mainly
      postjunctional events.

PMID- 11846961
TI  - Changes in red blood cell behavior during cerebral blood flow increase in the rat
      somatosensory cortex: a study of laser-Doppler flowmetry.
AB  - The purpose of this study was to investigate red blood cell (RBC) behavior during
      an increase in local cerebral blood flow (LCBF). We measured changes in RBC
      behavior by using laser-Doppler flowmetry (LDF) in alpha-chloralose-anesthetized
      rats. An increase in LCBF was carried out by approximately 2.5 and 4.0% CO(2)
      inhalation and activation of the somatosensory cortex. The activation of the
      cortex was induced by electrical stimulation of the hind paw with 1.5-mA pulses
      (0.1 ms) applied at frequencies of 0.2, 1, 5, and 10 Hz for a 5 s duration. The
      increases in LCBF and RBC velocity during both CO(2) inhalations were larger than
      that in RBC concentration (p < 0.05). LCBF and RBC velocity during 4.0% CO(2)
      inhalation were larger than those during 2.5% CO(2) inhalation (p < 0.05), though
      there was no significant difference in RBC concentration between the two
      conditions, suggesting a limitation of capillary volume. During somatosensory
      stimulation, the evoked LCBF increased with increasing stimulus frequency up to 5
      Hz and decreased at 10 Hz. The responses of RBC concentration at 0.2 and 10 Hz
      were greater than those of RBC velocity (p < 0.05), but no significant
      differences in response magnitude were found at 1 and 5 Hz between RBC
      concentration and RBC velocity. These results suggest that the increase in LCBF
      during neuronal activity is different from that of controlling the LCBF as
      induced by CO(2), and that the regulation of RBC concentration and RBC velocity
      is controlled by independent mechanisms.

PMID- 11846962
TI  - Rapid cardiac adaptation to exercise demand signal and execution of maximal leg
      muscle contraction.
AB  - We investigated the neural regulation of the cardiac interval to an exercise
      demand signal and to a repeated exercise in 20 healthy human subjects.
      Electrocardiogram (ECG), muscle torque, and electromyogram (EMG) were
      simultaneously measured and their time relationships compared before and during
      the exercise. The R-R interval of ECG was directly increased by the exercise
      demand signal itself before the onset of EMG but not reflexly by muscle
      contraction. The cardiac interval decreased at the onset of exercise. Under the
      condition of repeated maximum eccentric training, the resting cardiac interval
      decreased prior to the exercise, whereas the brief increase in cardiac interval
      to the exercise demand signal remained unchanged. These results suggested that
      when autonomic nerve activity to the pacemaker is activated by the exercise
      demand signal, an initial effect of vagal nerve activity appears, and an effect
      of vagal nerve withdrawal and/or sympathetic nerve activity then appears. The
      responses of the heart and leg skeletal muscle at the onset of exercise are not
      synchronized, and the cardiac interval is controlled by vagal and sympathetic
      nerve activities to effect a transition to a high heart rate as quickly and
      smoothly as possible.

PMID- 11846963
TI  - Rhythmic spontaneous contractions in the rat proximal colon.
AB  - C-kit immunoreactive cells are known to be interstitial cells of Cajal (ICCs),
      and they generate pacemaker activity of the gastrointestinal tract. Recently a
      large number of special smooth muscle cells corresponding to c-kit immunoreactive
      cells were found in the proximal colon of the guinea pig. We learned that the rat
      proximal colon showed tetrodotoxin-insensitive regular rhythmic spontaneous
      contractions (RSCs) and hypothesized that RSCs are generated and/or regulated by
      ICCs. To prove our hypothesis, we investigated whether RSCs are absent in
      homozygous Ws/Ws mutant rats, since c-kit positive ICCs along the submucosal
      surface of the circular muscle (ICC(SM)) and myenteric plexus (ICC(MY)) are
      lacking. In contrast to our hypothesis, we found that RSCs were still present in
      the proximal colon of the Ws/Ws mutant rats. A recent study has reported that c
      kit negative ICC(SM) remains in Ws/Ws mutant rats. Taken together, RSCs may be
      generated by c-kit negative ICC(SM) in the rat proximal colon. The blockade of
      sarcoplasmic reticulum Ca(2+)-ATPase by cyclopiazonic acid (CPA) (10(-6)M) or by
      thapsigargin (10(-6)M) increased the frequency of RSCs. The increasing effects of
      CPA on the frequency of RSCs were more prominent in Ws/Ws mutant rats than in +/+
      rats. We concluded that the functional coordination between c-kit negative
      ICC(SM) and other mutationally impaired c-kit positive ICC(MY) and ICC(SM) may be
      required for moderate regulation in the frequency of spontaneous activity.

PMID- 11846964
TI  - Properties of large conductance calcium-activated potassium channels in pyramidal
      neurons from the hippocampal CA1 region of adult rats.
AB  - The properties of large-conductance Ca(2+)-activated K(+) (BK(Ca)) channels were
      studied in rat hippocampal CA1 pyramidal neurons by using the patch-clamp
      technique in the excised-inside-out-patch configuration. The lowest [Ca(2+)](i)
      in which BK(Ca) channel activities were observed was 0.01 microM with the
      membrane potential of +20 mV and the [Ca(2+)](i) at which P(O) of the channel is
      equal to 0.5 was 2 microM. The unitary conductance of the single BK(Ca) channel
      was 245.4 pS with symmetrical 140 mM K(+) on both sides of the excised membrane.
      With a fixed [Ca(2+)](i) of 2 microM, P(O) increased e-fold with a 17.0 mV
      positive change in the membrane potential. Two exponentials, with time constants
      of 2.8 ms and 19.2 ms at the membrane potential of +120 mV with 2 microM
      [Ca(2+)](i), were required to describe the observed open time distribution of
      BK(Ca) channel, suggesting the existence of two distinct open channel states with
      apparently normal conductance. A BK(Ca) channel occasionally entered an apparent
      third open channel state with the single channel current amplitude about 45% of
      the normal amplitude. The properties of BK(Ca) channel, which were found in this
      study to be more steeply dependent on voltage and more sensitive to [Ca(2+)](i)
      in adult hippocampal neurons than in cultured or immature hippocampal neurons,
      may be responsible for the shortened duration of action potential in hippocampal
      CA1 pyramidal neurons of adult rat.

PMID- 11846965
TI  - Frank-Starling mechanism retains recirculation fraction of myocardial Ca(2+) in
      the beating heart.
AB  - Myocardial Ca(2+) handling in excitation-contraction coupling is the second
      primary determinant of energy or O(2) demand in a working heart. The
      intracellular and extracellular routes remove myocardial Ca(2+) that was released
      into the sarcoplasma with different Ca(2+): ATP stoichiometries. The
      intracellular route is twice as economical as the extracellular route. Therefore
      the fraction of total Ca(2+) removed via the sarcoplasmic reticulum, i.e., the
      recirculation fraction of intracellular Ca(2+) (RF), determines the economy of
      myocardial Ca(2+) handling. RF has conventionally been estimated as the
      exponential decay rate of postextrasystolic potentiation (PESP). However, we have
      found that PESP usually decays in alternans, but not exponentially in the canine
      left ventricle beating above 100 beats/min. We have succeeded in estimating RF
      from the exponential decay component of an alternans PESP. We previously found
      that the Frank-Starling mechanism or varied ventricular preload did not affect
      the economy of myocardial Ca(2+) handling. Then, to account for this important
      finding, we hypothesized that the Frank-Starling mechanism would not affect RF at
      a constant heart rate. We tested this hypothesis and found its supportive
      evidence in 11 canine left ventricles. We conclude that RF at a constant heart
      rate would remain constant, independent of the Frank-Starling mechanism.

PMID- 11846966
TI  - Development of renal potassium excretion capacity in the neonatal rat.
AB  - We investigated the capacity of newborn rats to excrete an acute potassium load
      to understand the development of a renal potassium excretion system. Three groups
      of the rats (7-14 d) were used to collect urine periodically over 6 h after oral
      infusion of potassium: control (no potassium loading) and low- and high-potassium
      loaded rats. In the low-potassium-loaded group, infused with about 0.6 microEq of
      potassium chloride/g body wt., the rate of renal potassium excretion increased
      from 0.08 plus minus 0.02 (7 d) to 0.13 plus minus 0.02 (10 d) and 0.21 plus
      minus 0.03 (14 d) microEq/h/g body wt. The high-potassium-loaded rats (1.5-2.8
      microEq/g body wt. potassium load) excreted potassium at a higher rate of 0.18 +/
      0.05 (7 d), 0.30 +/- 0.02 (10 d), and 0.45 +/- 0.10 (14 d) microEq/h/g body wt.
      They excreted 77% (7 d), 76% (10 d), and 95% (14 d) of the potassium load. These
      values were much larger than the rate of 0.026 microEq/h/g body wt. of the
      control rats and of 0.08 microEq/h/g body wt., a mean potassium excretion rate
      during development from 7 to 14 d calculated from the data in the previous study
      (Kanno T et al.: J. Pediatr. Gastr. Nutr. 24: 242-252, 1997). In the same period,
      serum potassium concentration in the newborn rats decreased significantly (p <
      0.01) from 7.2 +/- 0.1 (7 d) to 6.7 +/- 0.1 mEq/l (14 d). All these results
      suggest that a renal potassium excretion system in the rat develops at least in
      the second week of life, and its capacity is high enough to excrete the daily
      potassium intake.

PMID- 11846967
TI  - Effects of 17beta-estradiol on tension responses and fatigue in the skeletal
      twitch muscle fibers of frog.
AB  - The effects of 17beta-estradiol (10(-5) M), an active estrogen, on the tension
      and fatigue responses of single fiber or fiber bundle prepared from frog skeletal
      muscle were investigated. The administration of 17beta-estradiol caused a
      transient potentiation of tetanus tension by field stimulation at every minute.
      This potentiation was not affected by the presence of nicardipine, suggesting
      that the action of 17beta-estradiol would place the excitation-contraction (E-C)
      coupling beyond T-tubule depolarization. Fatigue was produced by repeated tetanic
      stimulation every second until tension declined to approximately 40% of the
      initial level. Fibers were then allowed to recover by having tetani given to them
      every minute. In the normal Ringer solution, the time to 50% of the initial
      tetanus tension was 41.7 s. With the presence of 17beta-estradiol, the time to
      50% tension was faster than that of control. The presence of 17alpha-estradiol, a
      stereoisomer, caused no potentiation of tetanic tension to be stimulated every
      minute, and the rate of decline of fatigued response was almost the same as that
      of control, suggesting the existence of specific estrogen receptors in the frog
      muscle. In fatigued muscle with or without estrogen, the tension to field
      stimulation was transient and not sustained. When the fatigued muscle was again
      treated with field stimulation at every minute after the more-frequent
      stimulation, the recovery rate was increased in 17beta-estradiol. A prompt
      reduction in temperature to 5 degree C, from 20 degree C, in the presence of
      caffeine elicited the tension response, a rapid cooling contracture (RCC). The
      presence of 17beta-estradiol inhibited peak tension and maximum rate of rise of
      the RCC only after the repetitive electrical stimuli. These results suggest that
      the potentiation of contraction upon the electrical stimulation by 17beta
      estradiol was induced by the increase of myoplasmic-free Ca(2+) concentration via
      an activation of some E-C coupling process. The 17beta-estradiol-induced
      facilitation of fatigue response to repetitive tetanus stimuli with high
      frequency may be due to an increase in the imbalance of Ca(2+) turnover in the
      cytoplasm.

PMID- 11846968
TI  - Caffeine ingestion attenuates the VO(2) slow component during intense exercise.
AB  - The purpose of this study was to analyze the effects of caffeine ingestion on the
      slow component of oxygen uptake (DeltaVO(2)) during high-intensity endurance
      exercise. Nine subjects (8 male and 1 female; age: 21 +/- 1 years; VO(2 max):
      57.9 +/- 1.5 ml kg(-1) min(-1)) performed two 9-min tests on a treadmill at a
      running velocity eliciting 90% of their VO(2 max), 60 min after ingesting either
      a placebo capsule (PLAC) or a capsule containing a caffeine dose of 5 mg (kg body
      mass)(-1) [CAFF]. The mean values of DeltaVO(2) were significantly lower in CAFF
      than in PLAC (83 +/- 31 ml min(-1) vs. 167 +/- 26 ml min(-1), respectively; p <
      0.05). These findings suggest that the ergogenic effect of caffeine in a high
      intensity endurance exercise shown in previous research may be partly mediated by
      a possible attenuation of the VO(2) slow component.

PMID- 11846971
TI  - Activities of IRF-1.
AB  - Interferon (IFN) regulatory factor-1 (IRF-1) was isolated by virtue of its
      affinity to specific DNA sequences in the IFN-beta promoter that mediate virus
      responsiveness. IRF-1 was the first factor identified of the IRF family and was
      most extensively characterized at the molecular level. Also, its physiologic role
      in host defense against pathogens, tumor prevention, and development of the
      immune system was investigated in detail. Even though some of the functions first
      associated with IRF-1 were later found to be mediated in part or predominantly by
      other activators of the IRF family of transcription factors, IRF-1 has remained a
      central paradigm in the transcriptional regulation of the IFN response.

PMID- 11846972
TI  - IRF and tuberculosis.
AB  - Tuberculosis is the most prevalent infectious disease and causes more deaths than
      any other, yet only 5%-10% of people infected by the causative agent,
      Mycobacterium tuberculosis, will develop the disease. Thus, natural resistance
      among humans is the norm. Fundamental immune responses to M. tuberculosis are
      being elucidated, including induction of interferon regulatory factor-1 (IRF-1).
      Moreover, IRF-1 has been found necessary for normal resistance to infection by
      mycobacteria in mice. Roles for IRF-1 in a plethora of immune system functions
      have been described. This review considers molecular responses to infection by M.
      tuberculosis that might account for induction of IRF-1 and highlights putative
      connections between immunomodulatory functions of IRF-1 and immune responses
      relevant to infection by M. tuberculosis. However, the complexity inherent in
      pleiotropy and redundancy limits the ability to draw firm conclusions. In many
      cases, it remains to be demonstrated that a particular function of IRF-1 is the
      basis for a known response to infection. For example, although IRF-1 is required
      for a Th1 cell-mediated, adaptive immune response in some circumstances, it is
      not known if the Th1 response to infection by M. tuberculosis requires IRF-1.
      Conversely, some known contributions by IRF-1 to fundamental aspects of the
      immune system are not yet proven relevant in the host response to infection. For
      example, it is not known if control of T cell subset development by IRF-1 is
      significant for host defense against M. tuberculosis. Functions of other IRF that
      overlap with or are distinct from the functions of IRF-1 also could be important
      for the immune response to M. tuberculosis.

PMID- 11846973
TI  - IRF regulation of HIV-1 long terminal repeat activity.
AB  - Interferon (IFN) regulatory factors (IRF) constitute a family of transcriptional
      activators and repressors implicated in multiple biologic processes, including
      regulation of immune responses and host defense, cytokine signalling, cell growth
      regulation, and hematopoietic development. All members are characterized by well
      conserved DNA binding domains at the N-terminal region that recognize similar DNA
      sequences termed IRF-binding element/IFN-stimulated response element (IRF-E/ISRE)
      present on the promoter of the IFN-alpha/beta genes and of some IFN-stimulated
      genes (ISG). Recently, a sequence homologous to the ISRE has been identified
      downstream of the 5' human immunodeficiency virus type 1 (HIV-1) long terminal
      repeat (LTR). This sequence is a binding site for IRF-1 and IRF-2. Deletion of
      the LTR-ISRE results in impaired LTR promoter activity and decreased synthesis of
      viral RNA and proteins. Here, we briefly summarize characteristics of IRF-1 and
      IRF-2 binding to the HIV-1 LTR-ISRE and the data obtained to date on the
      functionality of this cis-element and on the role of IRF in the regulation of HIV
      1 LTR transcriptional activity.

PMID- 11846974
TI  - IRF-1 as a negative regulator of cell proliferation.
AB  - Numerous evidence has demonstrated the involvement in growth control of
      interferon (IFN) regulatory factor-1 (IRF-1), which shows tumor suppressor
      activity. IRF-1 is a well-studied member of the IRF transcription factors that
      reveals functional diversity in the regulation of cellular response by activating
      expression of a diverse set of target genes, depending on the cell type and on
      the specific stimuli. IRF-1 gene rearrangements may be a crucial point in the
      pathogenesis of some cancer types. Furthermore, different aspects of the tumor
      suppressor function of IRF-1 may be explained, at least in part, by the
      observations that IRF-1 is a regulator of cell cycle and apoptosis and that its
      inactivation accelerates cell transformation. Studies on gene knockout mice
      contributed greatly to the clarification of these multiple IRF-1 functions. We
      summarize our current knowledge of the antigrowth effect of IRF-1, focusing also
      on a more general involvement of IRF-1 in mediating negative regulation of cell
      growth induced by numerous cytokines and other biologic response modifiers.

PMID- 11846975
TI  - Overlapping and distinct mechanisms regulating IRF-3 and IRF-7 function.
AB  - Recent molecular, biochemical, and gene disruption studies have demonstrated the
      essential role of interferon (IFN) regulatory factor-3, (IRF-3) and IRF-7 in the
      activation of type I IFN gene expression and the induction of the antiviral
      state. Both transcription factors share structural and functional properties, as
      well as a common mechanism of activation through C-terminal phosphorylation. The
      purpose of this review is to summarize recent investigations indicating that
      similar signalling pathways are likely involved in the activation of IRF-3 and
      IRF-7. Moreover, unique biochemical events, such as coactivator association and
      differential recognition of cis-acting elements, also illustrate the capacity of
      IRF-3 and IRF-7 to selectively regulate type I IFN and IFN-stimulated gene (ISG)
      expression.

PMID- 11846976
TI  - On the role of IRF in host defense.
AB  - Transcription factors of the interferon (IFN) regulatory factor (IRF) family have
      been shown to play an essential role in the regulated expression of type I IFN
      genes, IFN-stimulated genes (ISG), and other cytokines and chemokines. Three
      members of the IRF family, IRF-3, IRF-5, and IRF-7, have been identified as
      acting as direct transducers of virus-mediated signaling. In infected cells,
      these factors are activated by phosphorylation on the serine residues,
      transported to the nucleus, where they bind to the promoters of IFNA and IFNB
      genes and tether histone transacetylases to the transcription complex
      enhanceosome. IFNB and IFNA subtypes are expressed at different levels in
      infected cells. The ratio between the relative levels of IRF-3 and IRF-7 was
      shown to play an essential role in the inducible expression of type I IFN genes,
      whereas IRF-3 alone is sufficient for expression of the IFNB gene. IRF-5 was
      identified recently as another inducer of IFNA genes, which has two unique
      properties: (1) its activation is virus specific, and (2) the profile of IFNA
      genes induced by IRF-5 is distinct from that induced by IRF-7. Several viruses
      target functions of IRF to eliminate the early inflammatory response. Kaposi's
      sarcoma herpesvirus (KSHV) encodes a cluster of four genes with homology to
      cellular IRF. Three of these vIRF were shown to inhibit induction of IFN genes
      and ISG in infected cells and function as dominant negative mutants of cellular
      IRF. The unique properties of previously uncharacterized vIRF-2 and vIRF-3 are
      discussed.

PMID- 11846977
TI  - Control of IRF-3 activation by phosphorylation.
AB  - Interferon (IFN) regulatory factor-3 (IRF-3) is a unique member of the IRF
      family. Its transcriptional activity is regulated solely by posttranslational
      modifications. We review current knowledge of the mechanism of IRF-3 activation:
      signalling triggered by infections including viruses and bacteria,
      phosphorylation of IRF-3 on certain serine residues, homodimer formation, and
      active holocomplex formation with coactivator CBP/p300.

PMID- 11846978
TI  - The virus-induced factor VIF differentially recognizes the virus-responsive
      modules of the mouse IFNA4 gene promoter.
AB  - Maximal activation of murine infection-A4 (IFNA4) gene transcription following
      viral infection requires the presence of four cooperating DNA sequences (denoted
      A to D), which make up the virus responsive element VRE-A4. The B, C, and D
      modules, when tandemized, form binding sites for the virus-induced factor (VIF),
      a multiprotein complex that is detected early after viral infection in the nuclei
      of mouse L929 cells. We now demonstrate that IFN regulatory factor-3 (IRF-3) is a
      component of VIF and that VIF is different from the previously identified virus
      activated complexes containing IRF-3 and coactivators of transcription, such as
      CREB binding protein (CBP) or p300. We also show that the C module is critical
      for both IRF-3-mediated and virus-induced transcription of the murine IFNA4 gene.
      Consistently, DNase I footprinting experiments and EMSA performed with increasing
      amounts of recombinant GST-IRF-3(DBD) fusion proteins demonstrate that
      cooperativity between the modules facilitate the binding of IRF-3 and recruitment
      of transcription coactivators on the IFNA4 promoter. These results indicate that
      VIF differentially recognizes the virus-responsive modules of VRE-A4 and further
      actualize our previous model concerning the differential expression of murine
      IFNA genes.

PMID- 11846979
TI  - Enhancement and diversification of IFN induction by IRF-7-mediated positive
      feedback.
AB  - Interferons (IFN) are potent components of the innate immune response to
      microbial infection. The genes for type I IFN (IFN-alpha and IFN-beta) are
      rapidly induced in response to viral infection through a mechanism that involves
      latent cellular transcription factors that are activated in response to innate
      recognition of viral components. IFN regulatory factor (IRF) proteins are key to
      this regulation, and their conversion from latent to active involves virus
      induced serine phosphorylation. Differential utilization of distinct IRF proteins
      by different members of the type I IFN gene family produces a graded induction of
      gene expression, resulting in tight control of these cytokines through a positive
      feedback mechanism. Early response to virus causes secretion of a subset of IFN
      genes through the action of IRF-3 in conjunction with additional transcription
      factors, such as NF-kappaB and activator protein-1 (AP-1) (c-jun/ATF). This early
      IFN acts in an autocrine manner to stimulate production of IRF-7, a transcription
      factor capable of activating the many additional members of the IFN-alpha gene
      family. The dependence of IRF-7 on virus-induced phosphorylation for its activity
      insures that IFN production is limited to virus-infected cells. Characterization
      of the cellular components involved in viral detection and IRF activation will
      further delineate this vital mechanism of innate immune response.

PMID- 11846980
TI  - Structure and function of IRF-7.
AB  - Interferon (IFN) regulatory factors (IRF) are a family of transcription factors
      with multiple functions. IRF-7 was initially cloned within the biologic context
      of Epstein-Barr virus (EBV) latency and discovered to have an intimate relation
      with the EBV primary oncogenic protein, latent membrane protein-1 (LMP-1). EBV
      regulates and uses IRF-7 as a secondary mediator for several target genes
      involved in latency and immune regulation. Other than its functions in EBV
      latency, IRF-7 has been identified as one of the major players in virally induced
      IFN production that is central to innate immunity. Thus, IRF-7 plays important
      roles in a variety of biologic systems.

PMID- 11846981
TI  - Nuclear/cytoplasmic localization of IRFs in response to viral infection or
      interferon stimulation.
AB  - Members of the interferon (IFN) regulatory factor (IRFs) family of transcription
      factors play diverse roles in immunity and cellular response to viral infections.
      Their biologic effects result from their ability to regulate either constitutive,
      inducible, or tissue-specific gene expression. All characterized IRFs contain
      nuclear localization signals that allow their translocation to the nucleus.
      However, certain IRFs reside in a latent state in the cytoplasm of the cell and
      only redistribute to the nucleus following an activating trigger. IRF-3 and IRF-9
      are examples of IRFs that are regulated by cellular redistribution. These IRFs
      use distinct mechanisms that regulate nuclear/cytoplasmic localization, and both
      depend on strong interaction with non-IRF subunits of multimeric transcription
      complexes. This review compares the activation of IRF-3 and IRF-9 and their
      respective physiologic impacts.

PMID- 11846982
TI  - The role of IRF-4 in B and T cell activation and differentiation.
AB  - Appropriate activation and differentiation of lymphocytes are critical for
      effective immune responses. These processes are normally guided by exposure of
      lymphocytes to different stimuli, which need to be appropriately integrated in
      order for lymphocytes to proceed along their activation and differentiation
      pathways. Although the early steps in lymphocyte activation have been studied
      extensively, the downstream effectors of these activation pathways and the basic
      mechanisms employed by lymphocytes to integrate the information provided by
      different activation stimuli are not fully characterized. Interferon (IFN)
      regulatory factor-4 (IRF-4) is a recently described member of the IRF family of
      transcription factors whose expression is largely restricted to lymphocytes.
      Genetic studies have indicated that IRF-4 is critical for the function of mature
      T and B cells. Here we review the role of IRF-4 as a downstream effector and
      potentially an integrator of lymphocyte responses.

PMID- 11846983
TI  - The role of IRF-4 in transcriptional regulation.
AB  - Gene expression is a tightly regulated process involving multiple levels of
      control spanning histone acetylation to protein turnover. One of the first events
      in this cascade is transcription, which itself is a multistep process involving
      protein-protein interaction and macromolecular assembly. Here we review the role
      of the interferon (IFN) regulatory factor (IRF) transcription factor family
      member IRF-4 in transcriptional regulation. IRF-4 was initially characterized in
      lymphocytes and was shown to function as both a transcriptional repressor and
      activator. More recently, IRF-4 expression and function have been reported in
      macrophages. The ability of IRF-4 to serve as both a transcriptional activator
      and repressor is determined, in part, by binding to distinct DNA-binding motifs
      and through interaction with various additional transcription factors, most
      notably with the Ets family member PU.1. The details governing these functional
      differences are the focus of this review. Importantly, the role of
      posttranslational modification and nuclear translocation of IRF-4 in
      transcriptional regulation are addressed. Several possible paradigms of
      transcriptional regulation by IRF-4 are proposed, where these paradigms may
      describe regulatory mechanisms common to many distinct transcription factor
      families.

PMID- 11846984
TI  - IRF-4 activities in HTLV-I-induced T cell leukemogenesis.
AB  - We summarize recent studies on the activation and regulation of interferon (IFN)
      regulatory factor-4 (IRF-4) and its function in activated T cells, human T cell
      lymphoma virus (HTLV-I)-infected T cells, and HTLV-I-induced adult T cell
      leukemia (ATL). We have examined the specific mechanisms underlying the
      expression and regulation of the IRF-4 transcription factor in HTLV-I-infected
      cells and have shown that constitutive IRF-4 expression is exclusive to the
      transformed, leukemic ATL phenotype as opposed to the nonleukemic HTLV-I
      associated myelopathies/tropical spastic paraparesis (HAM/TSP) phenotype. In
      contrast, IRF-4 is only transiently induced in T lymphocytes activated by signals
      that mimic stimulation through the T cell receptor (TCR). In vivo and in vitro
      analyses have identified several regulatory regions within the human IRF-4
      promoter that interact with the transcriptional regulators NF-kappaB, NF-AT, and
      Sp-1 to drive IRF-4 production in HTLV-I-infected, ATL-derived cells. cDNA array
      analysis of an IRF-4-expressing T cell line has also provided valuable insight
      into potential IRF-4 target genes. Further investigation of these novel IRF-4
      regulated genes will permit a mechanistic understanding of IRF-4 function in HTLV
      I-induced leukemogenesis.

PMID- 11846985
TI  - ICSBP/IRF-8: its regulatory roles in the development of myeloid cells.
AB  - Interferon (IFN) consensus sequence binding protein (ICSBP)/IFN regulatory factor
      (IRF)-8 is an IFNgamma-inducible transcription factor of the IRF family and
      regulates transcription through multiple target DNA elements, such as IFN
      stimulated response element (ISRE), Ets/IRF composite element, and IFN-gamma
      activation site (GAS). ICSBP(-/-) mice are immunodeficient and susceptible to
      various pathogens. They have defects in the macrophage function, including the
      ability to induce interleukin-12 (IL-12) p40 and some IFN-gamma-responsible
      genes. In addition, ICSBP(-/-) mice develop a chronic myelogenous leukemia (CML)
      like syndrome, where a systemic expansion of granulocytes is followed by a fatal
      blast crisis. ICSBP(-/-) mice harbor an increased number of myeloid progenitor
      cells, and the -/- progenitors preferentially give rise to granulocytes, although
      they cannot efficiently generate another descendant of the myeloid lineage,
      macrophages. Studies with myeloid progenitor cells have shown that ICSBP drives
      their differentiation toward macrophage, whereas it inhibits granulocyte
      differentiation. Furthermore, myeloid cells from ICSBP(-/-) mice are resistant to
      apoptosis. These results illustrate the mechanism by which the loss of ICSBP
      leads to immunodeficiency and CML-like syndrome and suggest ICSBP's critical role
      in the development of myeloid cells.

PMID- 11846986
TI  - ICSBP/IRF-8 transactivation: a tale of protein-protein interaction.
AB  - Interferon (IFN) consensus sequence binding protein (ICSBP) is a member of a
      family of transcription factors termed IFN regulatory factors (IRF) and is also
      called IRF-8. Its expression is restricted mainly to cells of the immune system,
      and it plays a key role in the maturation of macrophages. ICSBP exerts its
      activity through the formation of different DNA-binding heterocomplexes. The
      interacting partner dictates a specific DNA recognition sequence, thus rendering
      ICSBP dual transcriptional activity, that is, repression or activation.
      Accordingly, such DNA elements were identified at the promoter regions of target
      genes that manifest macrophage action. A specific module (IRF association domain
      [IAD]) within ICSBP and a PEST domain located on the interacting partners mediate
      this association. Thus, ICSBP serves as an excellent prototype, demonstrating how
      a small subset of transcription factors can regulate gene expression in a
      spatial, temporal, and delicate tuning through combinatorial protein-protein
      interactions on different enhanceasomes.

PMID- 11846987
TI  - Status of animal alternatives for toxicology.

PMID- 11846988
TI  - Prediction models for eye irritation potential based on endpoints of the HETCAM
      and neutral red uptake tests.
AB  - The aim of this study was to explore the possibility of distinguishing between
      eye irritants (I; EU risk phrases R36 and R41) and nonirritants (NI), by using in
      vitro endpoints of the hen's egg test on the chorioallantoic membrane (the HETCAM
      test) and the neutral red uptake (NRU) test. Prediction models were derived by
      applying binary logistic regression to the in vitro data for these endpoints,
      which were taken from the report of a German validation study on the use of the
      HETCAM and 3T3 NRU tests as alternatives to the Draize eye irritation test.
      Whereas the validation study led to the conclusion that the combined use of the
      two tests enables a satisfactory discrimination between severe (R41) and
      nonsevere (NI, R36) eye irritants, the results of the present study indicate that
      the two in vitro tests can also be used to discriminate between nonirritants (NI)
      and irritants (R36 and R41).

PMID- 11846989
TI  - Assessment of the phototoxic potential of compounds and finished topical products
      using a human reconstructed epidermis.
AB  - The goal of this study was to design a model system for the assessment of
      phototoxic potential using a human reconstructed epidermis (HRE, SkinEthic
      Laboratories, Nice, France), by testing some representative phototoxic (P) and
      non-phototoxic (NP) compounds and finished topical products. The tissue response
      to 24-h application of 5-5000 microg/mL of the test agents in the presence and
      absence of UVA light was analyzed in terms of viability (Lactate Dehydrogenase
      release), pro-inflammatory activity (IL-8 release and mRNA expression) and
      morphology (histopathology). 8-Methoxypsoralen (P) and promethazin (P), but not
      sodium lauryl sulfate (NP) produced cytotoxicity concentration-response curves
      significantly different between irradiated and nonirradiated tissues. Only
      irradiated tissues showed morphological damage. Application of tetracyclin (P) in
      the culture medium, but not topically, induced similar signs of phototoxicity. 6
      Methylcoumarine (weak P) was not cytotoxic, yet it increased IL-8 release and
      mRNA expression only following UVA irradiation. PUVA therapy creams containing 1%
      8-Methoxy-psoralen (P) or coal tar (P) decreased viability and induced histologic
      damage in UVA-exposed tissues. In conclusion, the phototoxic potential of the
      tested agents was correctly predicted by using a tiered strategy that involves
      determining cytotoxicity, production of IL-8, and morphological damage following
      exposure of the HRE to the compounds and UVA light.

PMID- 11846991
TI  - Nile Red binding to HepG2 cells: an improved assay for in vitro studies of
      hepatosteatosis.
AB  - Nile Red is a fluorescent dye used extensively to study fat accumulation in many
      types of cells; unfortunately protocols that work well for most cells are not
      effective for studying drug-induced lipid accumulation in cultured liver cells
      and hepatocyte-derived cell lines. Using human hepatoma (HepG2) cells, we have
      developed a simple Nile Red binding assay as a screen for steatosis-inducing
      compounds. Increases in Nile Red binding in response to known hepatotoxic
      compounds were observed after incubating treated cells with 1 microM Nile Red for
      several hours, washing away free Nile Red, and then allowing redistribution,
      and/or clearance of the lipid-indicator dye. Several compounds known to cause
      hepatic fat accumulation in vivo were examined and most robustly increased Nile
      Red binding in HepG2 cells. These include estrogen and other steroids, ethionine,
      cyclosporin A, and valproic acid. Required concentrations for increased Nile Red
      binding were generally three-fold or more lower than the cytotoxic concentration
      determined by a resazurin reduction assay in the same cells. Qualitatively
      similar Nile Red binding results were obtained when primary canine or rat
      hepatocytes were used. Morphological differences in Nile Red staining were
      observed by confocal fluorescence microscopy in HepG2 cells after treatment with
      different compounds and likely reflect distinct toxicological mechanisms.

PMID- 11846990
TI  - Strategies for the in vitro testing of in situ polymers.
AB  - In situ polymers are used by mixing two or more compounds that are then placed
      directly in tissues to form a unique product. This type of reaction can generate
      heat, reactive oxygen species, free radicals, and other by-products of unknown
      toxicities, but the polymer itself is biocompatible. Many regulatory agencies
      require in vitro testing, however, standard guidelines (ASTM, ISO, AAMI) test
      polymers in a final form prior to use as a medical device. To better estimate the
      cytotoxicity of these in situ polymers, various means of introducing the reacting
      material to cells in culture were explored. Coating the material on a sterile
      glass cover slip then adding the cover slip to the in vitro test system
      immediately provided reasonable cytotoxicity data that reflected actual use
      conditions. For in situ polymeric devices that are more viscous, such as dental
      materials and bone cements, a mold was used that was placed directly into cell
      culture. This approach in testing in situ polymers generated in vitro toxicity
      data that reflects the actual use of the material.

PMID- 11846992
TI  - Comparative tissue-specific toxicities of 20 cancer preventive agents using
      cultured cells from 8 different normal human epithelia.
AB  - Comparative toxicity was determined for twenty potential chemopreventive agents
      in the Human Epithelial Cell Cytotoxicity (HECC) Assay using epithelial cell
      cultures from eight different tissues including: skin, kidney, breast, bronchus,
      cervix, prostate, oral cavity, and liver. The endpoints assessed were inhibition
      of: growth at 3 and 5 days; mitochondrial function; and proliferating cell
      nuclear antigen or albumin expression. Difluoromethylornithine (DFMO), s
      allylcysteine, dehydroepiandrosterone (DHEA) analogue 8543, l-selenomethionine,
      and vitamin E acetate were not toxic or only produced mild toxicity with all
      endpoints in all eight cell types. N-acetyl-l-cysteine, calcium chloride, DHEA,
      genistein, ibuprofen, indole-3-carbinol, 4-hydroxyphenylretinamide (4-HPR),
      oltipraz, piroxicam, phenylethyl isothiocyanate, 9-cis-retinoic acid, and p
      xylylselenocyanate each showed at least a 10-fold decrease in their TC(50) (toxic
      concentration that inhibited growth by 50%) for at least one endpoint with one or
      more cell types. For some agents such as DHEA and piroxicam, the TC(50)s for
      growth inhibition were 10-fold lower after 5 days compared with 3 days. Unique
      tissue-specific toxicity was observed for each toxic agent suggesting that tissue
      specific effects are the rule rather than the exception. The HECC Assay is
      effective in identifying tissue-specific toxicity for chemopreventive agents and
      may help to identify potential toxicity problems in phase I human clinical
      trials.

PMID- 11846993
TI  - Marked variation in free radical injury between bovine and porcine endothelial
      cells cultured in different media.
AB  - Previous studies produced models of oxygen-derived free radical (OFR) injury,
      using H(2)O(2) or xanthine/xanthine oxidase (X/XO), in cultured porcine aortic
      endothelium (PAE) and rat coronary endothelium. H(2)O(2) at 0.1 mM resulted in
      50% viability in both cell types. To determine if comparable H(2)O(2) or X/XO
      concentrations have the same injurious effect on endothelium from other sources,
      models of OFR injury were developed for bovine aortic endothelium (BAE) and
      bovine brain microvessel endothelium (BBME). Varying concentrations of H(2)O(2)
      (0.01 to 6 mM) or X/XO (10 microM/0.1 to 0.3 U/mL) were added to medium 24 h
      prior to evaluating cell damage. Injury was assessed using the Trypan blue
      exclusion test (% viability) and by measuring the release of lactate
      dehydrogenase into medium. H(2)O(2) concentrations required to produce 50%
      viability were >6 mM in BAE and BBME versus 1 mM in PAE when cells were grown in
      Dulbecco's modified Eagle's medium (DMEM). Similarly, BAE and BBME were less
      sensitive than PAE to damage by X/XO. Cells from both species were more sensitive
      to H(2)O(2) or X/XO injury when grown in Medium 199 (M199) versus DMEM. The most
      profound difference was observed with PAE where 50% viability was obtained with
      0.12 versus 1.05 mM H(2)O(2) in M199 versus DMEM. These results indicate that
      bovine endothelial cells from aorta and brain are more resistant to free radical
      injury than PAE. The presence or absence of key media components (iron, pyruvate,
      cysteine, histidine) likely influences the extent of OFR injury.

PMID- 11846994
TI  - Metallothionein protects against severe oxidative stress-induced apoptosis of
      human trophoblastic cells.
AB  - Oxidative stress induces cellular apoptosis. Many agents producing intracellular
      oxidative stress, including H(2)O(2) and steroid hormones, have also been found
      to induce metallothionein (MT) expression. Recently, MT has been recognized as
      potentially having antioxidant activity. This action may be essential for
      survival of terminally differentiated cells subject to oxidative stress, such as
      syncytiotrophoblasts, placental cells producing pregnancy hormones and forming
      the maternal-fetal barrier. We previously demonstrated an inverse relationship
      between basal MT expression and apoptotic incidence in the trophoblastic cell
      line, JEG-3. Using JEG-3 cells transfected with MT in sense or antisense
      orientation, we have examined here the effect of altered basal MT levels on
      trophoblastic function and apoptosis following treatment with H(2)O(2) or
      diethylstilbestrol (DES). Induction of MT mRNA was observed in control and
      transfected JEG-3 cells following exposure to severe oxidative stress. Changes in
      the localization of MT protein, however, were apparent after a low oxidative
      stress challenge. Exposure to H(2)O(2) resulted in a dose-dependent decrease in
      human chorionic gonadotropin secretion in all JEG-3 cultures regardless of basal
      MT expression, whereas no change was detected following DES treatment. With
      respect to apoptosis, a significant protective effect was observed proportional
      to the basal MT level. These results suggest that although MT does not ameliorate
      oxidative stress-induced perturbation of some trophoblastic functions, its
      expression is critical for protection of these cells from severe oxidative stress
      induced apoptosis. MT thus appears to act as an anti-apoptotic antioxidant in
      trophoblastic cells.

PMID- 11846995
TI  - Sedanolide, a natural phthalide from celery seed oil: effect on hydrogen peroxide
      and tert-butyl hydroperoxide-induced toxicity in HepG2 and CaCo-2 human cell
      lines.
AB  - Sedanolide is a natural compound occurring in edible umbelliferous plants. Celery
      seed oil, a significant source of sedanolide, is used as an herbal remedy to
      treat inflammatory-associated conditions such as gout and rheumatism. The
      objective of this study was to assess the potential protective properties of
      sedanolide against hydrogen peroxide (H(2)O(2))- and tert-butyl hydroperoxide
      (tBOOH)-induced toxicity in HepG2 and CaCo-2 cells. Viability of HepG2 and CaCo-2
      cells was unaffected by a 24-h exposure to sedanolide (7-500 microM), however,
      when the cells were cultured in sedanolide-free medium for a further two cell
      cycles (72 h), a decrease in cell viability was observed for HepG2 cells
      previously exposed to 500 microM of the compound. Cells pretreated with
      sedanolide (100 microM for 24 h) and exposed to either H(2)O(2) or tBOOH did not
      exhibit statistically significant difference in viability from controls. A
      significant increase (p < 0.05) in DNA strand breaks, as measured by the comet
      assay, was observed in HepG2 but not CaCo-2 cells following a 24-h incubation
      with 500 microM sedanolide. Sedanolide did not modulate H(2)O(2)- and tBOOH
      induced DNA damage. Sedanolide is relatively nontoxic to cells in culture,
      however, the protection it afforded against H(2)O(2)- and tBOOH-induced toxicity
      was not statistically significant.

PMID- 11846996
TI  - Effect of dimethoate on the function and expression of nicotinic acetylcholine
      receptor in primary skeletal muscle cell culture.
AB  - To investigate the molecular mechanism of intermediate myasthenia syndrome (IMS),
      we analyzed the toxic effects of the representative organophosphate dimethoate on
      the function and expression of the nicotinic acetylcholine receptor (nAChR) in
      primary skeletal muscle cell culture. The results showed that the expression of
      nAChR on the muscle cell membrane was significantly increased after cells were
      exposed to dimethoate (130 microM). AChR function measured by carbachol-induced
      (22)Na+ influx demonstrated that dimethoate may inhibit the nAChR function either
      by binding to a noncompetitive site and changing the conformational state of
      nAChR or by blocking the nAChR channel directly. This study also demonstrated
      that dimethoate could rapidly induce the expression of c-fos, with a maximal
      effect at about 40 min, and c-fos might act as a transcriptional factor in
      regulating the expression of nAChR in the primary skeletal muscle cell culture
      following organophosphate exposure.

PMID- 11846999
TI  - Preliminary note on the differentiation of angioblasts and the method by which
      they produce blood-vessels, blood-plasma and red blood-cells as seen in the
      living chick. 1917.
AB  - Reprinted from The Anatomical Record, Vol. 13, pp. 199-204, 1917.

PMID- 11847000
TI  - The search for the hemangioblast.

PMID- 11847001
TI  - Fibroblast growth factors and their receptors in hematopoiesis and hematological
      tumors.
AB  - Fibroblast growth factors (FGFs) belong to a family of pleiotropic heparin
      binding growth factors. They exert multiple functions on various cell types of
      mesodermal and neuroectodermal origin, affecting cell proliferation, motility,
      survival, and differentiation. FGF's exert their activity by interacting with
      tyrosine kinase receptors (FGFRs) and cell-surface heparan sulfate proteoglycans.
      This article reviews recent studies on the role of the FGF/FGFR system in
      embryonic hematopoietic development, hematopoiesis, and hematological tumors.
      FGFs exert both autocrine and paracrine functions in these biological processes
      by acting on blood cells and their precursors and accessory cells in the bone
      marrow, including stromal and endothelial cells.

PMID- 11847002
TI  - A review of angiogenesis and anti-angiogenic therapy in hematologic malignancies.
AB  - Tumor angiogenesis is currently not only a concept but has also become a
      rationale for the therapeutic use of both old and new drugs that might affect new
      blood vessel formation. There is growing evidence that angiogenesis is as
      important in hematologic malignancies as it is in solid tumors. Both myeloid and
      lymphoid disorders may be accompanied by a prognostically detrimental increase in
      bone marrow microvessel density. In this review, we summarize the current
      literature as well as our own studies regarding bone marrow angiogenesis and the
      use of anti-angiogenic treatment in hematologic disorders. Background information
      on pathogenesis and laboratory methods of quantifying bone marrow angiogenesis is
      also discussed.

PMID- 11847003
TI  - The role of angiogenesis in hematologic malignancies.
AB  - Several reports have highlighted the biologic relevance of angiogenesis in
      neoplastic disorders and its potential impact on prognosis. In this review, we
      focus on recent findings about angiogenesis and angiogenetic factors in
      hematologic malignancies. We summarize the body of evidence supporting the
      hypothesis that a common progenitor gives rise to cells of both the endothelial
      and the hematopoietic lineages, and the current knowledge about the involvement
      of normal stromal cells in bone marrow angiogenesis. We also discuss the
      methodological aspects of microvessel count as a measure of tumor angiogenesis.
      Finally, we describe the current therapeutic role of angiogenesis inhibitors and
      possible future strategies involving these agents.

PMID- 11847004
TI  - Phenotypic overlap between hematopoietic cells with suggested angioblastic
      potential and vascular endothelial cells.
AB  - The existence of angioblast-like circulating endothelial progenitor cells (EPC)
      in adult humans has been suggested recently. Their role in postnatal angiogenesis
      is under intensive investigation. Discrimination between the supposed angioblasts
      (AC133(+)/FLK-1(+)/CD34(+)) and mature endothelial cells (ECs) is complicated by
      the fact that subsets of hematopoietic cells express markers similar to those of
      ECs. Among these, monocytes/macrophages and monocyte-derived dendritic cells
      (DCs) are more differentiated hematopoietic cell populations. They show a wide
      phenotypic overlap with particularly sinusoidal and microvascular ECs.
      Furthermore, under local angiogenic growth conditions, monocytes or monocyte
      precursors or immature DCs may differentiate into endothelial-like cells (ELC).
      Initial evidence suggests an endothelium-independent revascularization potential
      carried by macrophages. These macrophages have been shown to form "tunnel-like
      structures" in ischemic regions. Future studies will need to address the question
      of whether monocyte-/dendritic cell-derived ELC can develop a similar functional
      behavior in vasoregulation, coagulation, and fibrinolysis, as described for
      vascular ECs, and thus may contribute to neoangiogenesis by a direct vessel
      forming role.

PMID- 11847006
TI  - The hemangioblast: a common progenitor of hematopoietic and endothelial cells.
AB  - In the developing embryo, the initial hematopoietic and vascular structure can be
      identified as the blood islands of the yolk sac. Blood islands are formed from
      mesodermal aggregates that have migrated from the primitive streak. The outer
      cells differentiate into endothelial cells and the inner to primitive blood. The
      close developmental association between hematopoietic and endothelial cell
      lineages has led to a hypothesis that they share a common progenitor, the
      hemangioblast. This review will examine emerging studies supporting the existence
      of such cells in order to further understand how the hematopoietic and vascular
      systems are established during mouse development.

PMID- 11847005
TI  - Endothelial cell heterogeneity and organ specificity.
AB  - Endothelial cells consist of a heterogeneous population covering the entire inner
      surface of blood vessels. This review will focus on the factors influencing this
      heterogeneity including: (1) morphological and functional differences between
      large and small vessels and between cells derived from various microvascular
      endothelial beds; (2) the microenvironment and extracellular matrix modulating
      the phenotype; (3) different response to growth factors; (4) organ specificity
      reflecting the cumulative expression of post-translation modifications and also
      the expression of unique genes under the control of organ-specific regulatory
      elements; and (5) pathological conditions, such as tumor growth, which is
      accompanied by the development of a characteristic tumor vasculature and tumors
      formed by endothelial cells.

PMID- 11847007
TI  - Docetaxel versus paclitaxel for antiangiogenesis.
AB  - Cytoskeleton-toxic chemotherapeuticals, such as vinblastine and paclitaxel,
      display antiangiogenic activity. This study was designed to compare paclitaxel to
      its analog docetaxel and assess their doses still antiangiogenic in vitro and in
      vivo. Human endothelial cell functions involved in angiogenesis, namely
      proliferation, chemotaxis, morphogenesis, and secretion of matrix
      metalloproteinase-2 (MMP-2), MMP-9, and urokinase-type plasminogen activator
      (uPA) were studied in vitro upon exposure to docetaxel and paclitaxel, whereas
      their effect on angiogenesis was studied in vivo by using the chick embryo
      chorioallantoic membrane (CAM) model. Proliferation of mouse embryo fibroblasts
      and human Kaposi's sarcoma, breast and endometrial carcinoma, and lymphoid tumor
      cells was also studied. In vitro, 0.5, 0.75, and 1 nM docetaxel and 2, 3, and 4
      nM paclitaxel, i.e., non-cytotoxic doses, impacted all endothelial cell
      functions, but not protease secretion, in a dose-dependent fashion, whereas they
      did not affect the proliferation of other cells, except those of Kaposi's
      sarcoma. No apoptosis was induced by 0.5 nM docetaxel and 2 nM paclitaxel, and
      moderate apoptosis was induced by 1 nM docetaxel and 4 nM paclitaxel. The
      antiangiogenic effect rapidly disappeared on drug suspension and was accompanied
      ultrastructurally by thin lesions of cytoskeleton in the form of slight and
      equally reversible depolymerization and accumulation of microfilaments. Massive
      endothelial cell apoptosis with evident cytotoxicity and irreversibility were
      associated with 2 nM docetaxel and 5 nM paclitaxel, although these higher doses
      were ineffective on other cells except Kaposi's sarcoma cells. In vivo, 1, 2, and
      3 nM docetaxel and 4, 8, and 12 nM paclitaxel displayed a dose-dependent
      antiangiogenic activity. We suggest that very low docetaxel and paclitaxel doses
      selectively cause organic and functional damage of endothelial cells and that
      docetaxel is four times stronger. Their antiangiogenic activity could be applied
      to treat Kaposi's sarcoma and cancers.

PMID- 11847008
TI  - Blood levels of angiogenin and vascular endothelial growth factor are elevated in
      myelodysplastic syndromes and in acute myeloid leukemia.
AB  - Angiogenesis is of prognostic importance not only in solid tumors but also in
      malignant blood diseases. We measured levels of vascular endothelial growth
      factor (VEGF), angiogenin (ANG), and basic fibroblast growth factor (bFGF) in
      peripheral blood samples from 65 patients with myelodysplastic syndrome (MDS),
      from 25 patients with de novo acute myeloid leukemia (AML), and from 50 healthy
      donors. In matched samples, VEGF levels in serum were substantially higher than
      VEGF levels in plasma (380.7 +/- 56 pg/ml vs. 45.3 +/- 4.5 pg/ml, mean +/- SEM, p
      < 0.001), whereas serum and plasma levels of ANG were comparable and
      significantly correlated (r = 0.8; p < 0.01). Compared to normal controls (1.3 +/
      0.09 pg), serum levels of VEGF corrected for the peripheral blood platelet count
      (VEGF/10(6) platelets, VEGF(PLT)) were elevated in patients with refractory
      anemia (RA; 3.1 +/- 0.8 pg, p < 0.01), and reached maximal values in patients
      with advanced stage MDS (RAEB, RAEB-t) (3.5 +/- 0.6 pg, p < 0.001), de novo AML
      (3.6 +/- 1.1 pg, p < 0.05), and chronic myelomonocytic leukemia (CMML; 3.7 +/-
      0.9 pg; p < 0.001). Levels of soluble ANG were elevated in RA (351 +/- 25.7
      ng/ml, p < 0.001), in RAEB/RAEB-t (402 +/- 17.9 ng/ml; p < 0.001), in CMML (413.8
      +/- 29.5 ng/ml; p < 0.001), and in patients with AML (305.1 +/- 17.1 ng/ml; p <
      0.01, controls 255.4 +/- 8.1 ng/ml). Serum bFGF was neither elevated in MDS nor
      in AML patients. These results suggest that VEGF(PLT) is a marker of disease
      progression in MDS. Moreover, we show for the first time that elevated blood
      levels of ANG can be found in patients with myeloid malignancies, suggesting a
      role of ANG in the pathogenesis of these diseases.

PMID- 11847010
TI  - Bone marrow angiogenesis in systemic mast cell disease.
AB  - Mast cells may participate in tumor angiogenesis through the release of
      angiogenic cytokines from their secretory granules. To gain additional insight
      into the role of mast cells in bone marrow angiogenesis, we performed a
      semiquantitative measurement of bone marrow microvessel density in 52 consecutive
      adult patients with systemic mast cell disease (SMCD). The results were examined
      for potential correlations with mast cell expression of angiogenic cytokines and
      with other histologic features of the bone marrow. Standard immunohistochemical
      methods were used to visualize bone marrow microvessels (CD34 staining) and mast
      cell expression of transforming growth factor-beta, basic fibroblast growth
      factor, and their respective receptors. An increase in microvessel density was
      demonstrated in 32 of the 52 patients (62%) with SMCD, and the degree of bone
      marrow angiogenesis did not correlate with either the mast cell expression
      pattern of the study cytokines or the presence (23 patients) or absence (29
      patients) of an associated hematologic disorder. In the 29 patients without an
      associated hematologic disorder, microvessel density was correlated significantly
      with the presence of an abnormal pattern of hematopoiesis but not with the degree
      of bone marrow involvement by mast cells. Furthermore, areas occupied by mast
      cell lesions were often devoid of neovascularization. We conclude that bone
      marrow angiogenesis characterizes a percentage of patients with SMCD and that the
      pathogenesis may not necessarily be linked to the mast cells themselves.

PMID- 11847009
TI  - Ex vivo expansion of stem and progenitor cells in co-culture of mobilized
      peripheral blood CD34+ cells on human endothelium transfected with adenovectors
      expressing thrombopoietin, c-kit ligand, and Flt-3 ligand.
AB  - To optimize conditions for ex vivo expansion of adult hematopoietic stem cells,
      we evaluated the co-culture of G-CSF mobilized human peripheral blood (PB)
      CD34(+) cells with endothelial cells engineered to overexpress various
      hematopoietic growth factors. Immortalized human bone marrow endothelial cells
      (BMEC) transfected with an expression vector carrying cDNA encoding the human
      telomerase reverse transcriptase (hTERT) and human umbilical vein endothelial
      cells (HUVEC) were transfected with combinations of adenovectors expressing
      murine c-kit ligand (KL), human thrombopoietin (TPO), human Flt3 ligand (FL), and
      human granulocyte-macrophage colony-stimulating factor (GM-CSF). Ex vivo
      expansion of PB CD34(+) cells from normal donors and non-Hodgkin lymphoma (NHL)
      patients in endothelial co-culture was evaluated weekly for total cell
      production, progenitor (CFU-GM, BFU-E) cell production, and stem cell production
      as measured by Week-5 Cobblestone Area Forming Cell assay (Wk-5 CAFC). HUVEC
      transfected with adenovectors expressing TPO, KL, and FL provided the best co
      culture system for expanding CD34(+) cells. Maximal total nuclear cell, CFU-GM,
      and Wk-5 CAFC production occurred between weeks 2 and 3 with 113-fold, 25-fold,
      and 2.2-5.5-fold expansions, respectively. We did not detect significant
      differences when GM-CSF was added to the co-culture system. Expansion was also
      obtained using recombinant human cytokines, but was not maintained beyond 3
      weeks. We demonstrated that continuous generation of high levels of TPO, FL, and
      KL as well as other factors secreted by endothelium provided a clinically
      relevant co-culture method for ex vivo expansion of stem and progenitor cells
      from cryopreserved CD34(+) populations.

PMID- 11847011
TI  - Circulating endothelial adhesion molecules (sE-selectin, sVCAM-1 and sICAM-1)
      during rHuG-CSF-stimulated stem cell mobilization.
AB  - The role of leukocyte-endothelial cell interactions during granulocyte colony
      stimulating factor (G-CSF)-induced stem cell mobilization is unclear. To examine
      endothelial activation during this process, we determined levels of circulating
      endothelial adhesion molecules in healthy donors undergoing G-CSF-mobilized stem
      cell collection. Plasma levels of soluble (s) E-selectin, soluble intercellular
      adhesion molecule-1 (sICAM-1), and soluble vascular cell adhesion molecule-1
      (sVCAM-1) were serially determined by enzyme-linked immunosorbent assays in 10
      healthy donors during G-CSF-stimulated stem cell mobilization. There was a
      significant increase in plasma levels of all three endothelial adhesion molecules
      (sE-selectin, p = 0.01; sICAM-1, p = 0.003; sVCAM-1, p = 0.0002) between day 1
      and day 5 of G-CSF stimulation, but only sVCAM-1 concentrations exceeded the
      range obtained from unstimulated controls in all stem cell donors. Increases of
      sCAM were accompanied by increased numbers of white blood cells and CD34(+)
      progenitors in peripheral blood. G-CSF-stimulated peripheral blood progenitor
      cells (PBPC) mobilization results in increased levels of circulating endothelial
      adhesion molecules that were most evident for VCAM-1 molecules. Because soluble
      VCAM-1 remains active in binding to the VLA-4 receptor on CD34(+) cells, it may
      reduce stem cell adhesiveness to endothelial cells and to bone marrow
      microenvironment.

PMID- 11847012
TI  - Bone marrow-derived endothelial cells for therapeutic angiogenesis and
      antiangiogenesis: facts and visions.

PMID- 11847016
TI  - Abstracts Presented at the Spring Meeting of the Society for Education in
      Anesthesia.

PMID- 11847015
TI  - New year, new editor, new location, new format, new world.

PMID- 11847019
TI  - [Knowledge and experience].

PMID- 11847020
TI  - [Molecular mechanisms of oncogenic transformation: what's new?].
AB  - During the past two years, new molecular targets have been discovered which link
      cell cycle, cell proliferation and cellular growth. It has become more and more
      evident that whereas gain-of-function mutations in specific genes can lead to
      cancer, genomic instability plays also an important role in tumour progression.
      With examples taken from the recent literature, we describe in this short review
      crucial findings on the molecular mechanisms controlling cell cycle and
      proliferation. We illustrate how specific combinations of proto-oncogenes
      alterations can result in tissue-specific tumours. Finally, impairment of the
      interactions of a cancer cell with its surrounding neighbours is also shown to
      participate in the progression toward aggressive phenotypes.

PMID- 11847021
TI  - [New concepts for the study of anticancer drug resistance].
AB  - In the past decade, numerous mechanisms of resistance have been described,
      involving the availability of the drug at the target or the availability of the
      target itself, but resistance to cell death induction remains far from being
      understood. The involvement of p53, of Bcl2 and related proteins, of the Fas/Fas
      L system and other membrane death receptor pathways, have especially been
      studied. However, conflicting results have been published concerning the
      impairment of apoptosis in resistance to cytotoxic drugs. This has shed important
      doubts on the currently accepted view, which presents apoptosis as a universal
      determinant of drug activity. These discrepancies are likely to be related to the
      cell-type specificity of apoptotic pathways and further research is warranted to
      get a complete picture of the role of cell death inhibition as a drug resistance
      mechanism. New genetic tools have been recently made available for the study of
      anticancer drug resistance. Differential or subtractive analyses of gene
      expression in drug-sensitive and drug-resistant cell lines or tumors have allowed
      the identification of genes which are potentially responsible for drug
      resistance, and which had not been recognized previously by the usual analytic
      approaches. The generation of genetic suppressor elements represents a more
      functional approach since they can be selected upon the actual resistance
      properties of the cell lines. Global transcriptome analysis can be performed
      through the use of cDNA microarrays, either for the comparison of drug-sensitive
      and resistant cell lines, or for the study of drug effects on gene expression.
      This may allow the identification of drug-response genes (whose expression is
      altered by the drug) and of signaling and metabolic pathways involved in drug
      activity.

PMID- 11847022
TI  - [PPARdelta and PPARgamma: roles in fatty acids signalling, implication in
      tumorigenesis].
AB  - Numerous evidences have demonstrated the relationship between high fat diets and
      onset and/or progression of several diseases associated with obesity. Moreover,
      several studies have shown that dietary fat generally increases cancer risk.
      Fatty acids also play a crucial role in the development of these pathologies. The
      nuclear receptors PPARgamma and PPARdelta are molecular targets for fatty acids.
      These receptors exert opposite actions in the tumorigenesis process. Indeed,
      whereas fatty acids-activated PPARdelta is implicated in cellular proliferation
      and appears to play some role in tumor onset, the activation of PPARgamma by
      fatty acids or some of their metabolites, seems to counteract tumor progression.
      Then, PPARgamma and PPARdelta could constitute new potential pharmaceutical
      targets for cancer treatment.

PMID- 11847023
TI  - [Update on . . . the proteasome inhibitor PS341].
AB  - The proteasome degradation system is one of the most efficient proteolytic
      process in living cells. We will focus here on a new compound, called PS341,
      which is the first proteasome inhibitor entering clinical phases. First results
      about its use in multiple myeloma or leukemic cells will be discussed.

PMID- 11847024
TI  - [Update on renal cell carcinoma].
AB  - Authors have selected and presented radiofrequency tissue ablation for primary
      renal tumors and cellular therapy with dendritic cells or nonmyeloablative
      allogeneic transplantation as the main results in 2000-2001 on renal cell
      carcinoma. Furthermore other points are developed as hypertension increasing the
      risk of renal cell carcinoma, chromosomal events until renal cell carcinoma and
      prognosis of incidentally detected tumors.

PMID- 11847025
TI  - [Update on screening, diagnosis and treatment of cancer of the prostate].
AB  - Recent progress in management of prostate cancer concern screening and treatment.
      The use of PSA and rectal examination advances the diagnosis by 5 to 10 years and
      shift the stage at the time of diagnosis toward curative localized intraprostatic
      disease. The impact of systematic screening remains controversial. However,
      individual screening explains, at least in part, the decrease of specific
      mortality due to prostatic cancer, recently observed in USA. PSA and
      lymphadenectomy have also contributed to a better selection of patients referred
      for local treatment by prostatectomy or radiotherapy. Radical prostatectomy is
      recommended for patients before 70 with T2 or less, Gleason score less than 8 and
      PSA less than 15 ng/ml. With that selection, disease-free survival reaches 75 to
      80% at 10 years. Recently, dramatic improvement in radiotherapy techniques have
      been achieved, leading to a better local control by increasing the dose over 70
      Gy without additional toxicity. Brachytherapy is also widely used for good
      prognosis localized disease. Limitant acute urinary side effects have been
      reported and results seem similar to those reported after prostatectomy or
      conformal radiotherapy. Recent randomized trials have demonstrated a benefit of
      early hormonal therapy concurrent with radiotherapy for patients with poor
      prognosis localized disease. For hormonoresistant metastatic disease,
      chemotherapy has been used with limited palliative benefit. New drugs are
      currently evaluated.

PMID- 11847026
TI  - [Update on about testicular cancer].
AB  - The last two years publications are mainly concerning the following themes: the
      detection of testicular tumor for high risk patients. The treatment of stage one
      non seminomatous germ cell tumors is also detailed with reference to the three
      therapeutic options. The surgical treatment is evoked through laparoscopic
      surgery, surgery of residual masses and salvage surgery. Recent acquisitions in
      chemotherapy matters allow a simplification of protocols. They induced an
      improvement in the patient's quality of life with an equivalent efficiency. The
      salvage chemotherapy is evaluated and its results are assessed. The innovations
      in imaging are essentially focused on position emission tomography in the
      evaluation of these tumours but also on magnetic resonance imaging.

PMID- 11847027
TI  - [Recent progress and perspectives in the management of patients with lung
      cancer].
AB  - Lung cancer is still actually a leading cause of death in industrial countries,
      while the major etiologic agent, the tobacco smoke, is clearly identified.
      Primary or secondary prevention's strategies are frequently unsuccessful. The
      main survival chance is an early diagnosis of the disease. Efforts in the lung
      cancer screening have to be continued. Therapeutic strategies improved but
      progress in terms of survey are disappointing. Hopes relies on new drugs
      development coming from fundamental research, for whom first clinical trials are
      ongoing.

PMID- 11847028
TI  - [Current insights in malignant pleural mesothelioma].
AB  - Faced with the rising incidence of malignant pleural mesothelioma (MPM), the
      medical community is now busy to improve the care for this pathology. Although
      there is still no unanimously recognized therapy for MPM, long survival has been
      observed for some patients treated with associated therapies (surgery +
      radiotherapy + chemotherapy). However, the detection and the aggressive care of
      early stages MPM must be justified by a demonstrated survival improvement with
      conservation of a good quality of life. This article tries to summarize current
      insights concerning epidemiology, diagnosis and treatment of MPM. At now, more
      questions than responses exist concerning the care of this severe prognosis
      disease.

PMID- 11847029
TI  - [Update on malignant hemopathies].
AB  - The beginning of this century was marked, in our specialty as in other, by two
      revolutions: the routine use of molecular biology tools for a better prognosis of
      the disease (flt3 receptor duplication in AML, mutational profile of Ig genes in
      CLL, gene expression profile with ARN chips in aggressive lymphomas.), and the
      discovery of "intelligent" molecules, targeting the tumoral cell. In this
      category, the most appealing is the STI571 (Gleevec , Novartis), targeting the
      molecular abnormality of the cells expressing bcr-abl protein: CML, ALL Ph1(+).
      Other molecules targeting signal transduction proteins (ras farnesylation
      inhibitors for example) are already in clinical trials. The increasing
      therapeutic use of monoclonal antibodies is also to be cited, with a special
      mention concerning the rituximab, used in several B lymphoid pathologies, from
      lymphoma to autoimmune diseases. His very good tolerance permits his use in
      ambulatory patients, and his combination with chemotherapy or his linkage with
      radioactive elements render this molecule indispensable. The other side of these
      molecules is their incredibly high cost, explaining the uncontrolled expenses in
      2001 of hospitals hosting hematology as well as oncology activities.

PMID- 11847031
TI  - [Update on soft tissue sarcomas].
AB  - Important refinements have taken place in the diagnosis of soft tissue sarcoma
      with extensive use of immuno-histochemistry. New entities have been described,
      while malignant histiocytofibroma, the most diagnosed sarcoma type during the
      last two decades, has been dismembered. As for prognosis, the new UICC
      classification is effectively more discriminating in the definition of prognostic
      groups; but the usefullness of new biological or genetic markers remains to be
      assessed. Several breakthrough have taken place in the last years in the
      treatment of soft tissue sarcoma. Isolated limb perfusion with TNF, hyperthermia
      and melphalan have proven its efficacy, and is now an alternative to preoperative
      chemotherapy and/or radiotherapy for limb sparing treatment of the primary tumor
      site or to amputation. For systemic treatments, novel cytostatic drugs have been
      shown to be active in sarcomas, including ecteinascidine (ET743) and Glivec
      (STI571). This last drug has been shown to be remarkably active in c-kit+ stromal
      sarcoma of the gastro-intestinal tract. It can hopefully regarded as an example
      for targeted therapies, which may come with a better understanding of the
      molecular mechanisms triggered by the fundamental, specific genetic alterations
      shown in sarcoma.

PMID- 11847030
TI  - [Update on lymphomas].
AB  - Important progress have been recently achieved in the management of Hodgkin's
      disease (HD) and non-Hodgkin's lymphoma (NHL). Prognostic factors are now better
      defined in HD thanks to new biologic and radiologic information which complete
      old and relevant clinical factors. These parameters are expected to improve
      decision making in patient's management. However, treatment strategy is under new
      discussion and controversies about the role of radiotherapy and its doses. There
      are now enough arguments to consider radiotherapy unnecessary in advanced stages
      when a complete remission is achieved by chemotherapy. There is also important
      concern about late effects of treatment and not only secondary cancers. Non
      Hodgkin's lymphomas are heterogeneous and different entities are now better
      defined and described, thanks to a common and similar language for immunological
      clinical data and treatment outcome. New strategies are under investigation using
      monoclonal antibodies with or without radioisotopes, in association with
      chemotherapy or radiotherapy. Undoubtedly, these new approaches are going to
      improve the overall prognosis of NHL.

PMID- 11847032
TI  - [Update on rhabdomyosarcomas in children].
AB  - Rhabdomyosarcoma is a rare tumour corresponding to 60-70% of soft tissue sarcomas
      in children. Significant advances in treatment have been made possible, and will
      be further obtained, by multicentric treatment protocols conducted in paediatric
      oncology centres. Overall survival and disease-free survival have been
      significantly improved over the past 30 years. In the meantime, diagnosis
      improvements have made the classification of rhabdomyosarcomas more complex. A
      review of European and American studies has evidenced a number of criteria that
      should be taken into account for selecting treatment strategy: histological
      examination (refined with the use of molecular biology) had proved very
      informative, suggesting a worse prognosis for alveolar rhabdomyosarcomas. Other
      criteria of interest are the tumour site (favourable or unfavourable), patient
      age (under or above 10), tumour size (  5 cm), and disease stage. The number of
      sub-groups of patients requiring different, more adapted treatment strategies
      increases with the number of prognostic parameters to be considered. For
      convenient clinical management, patients will therefore be classified into 4 risk
      groups for systemic therapy (low, standard, high and very high risk), whereas
      local treatment strategies will take into account the whole set of prognostic
      criteria defined above.

PMID- 11847034
TI  - [Cancer update on breast reconstruction].
AB  - Breast reconstruction is evolving towards immediate reconstruction (IBR).
      Adjuvant radiotherapy remains an esthetical contraindication to classical
      techniques due to complication rate (capsular contracture, flap necrosis and
      contracture). Tissue expansion combined with radiotherapy must be evaluated. IBR
      quality of life raises the issue of its evaluation. IBR current limits seem to be
      psychological. The quality of preoperative information will determine IBR real
      life experience.

PMID- 11847033
TI  - [Update on differenciated thyroid carcinoma].
AB  - Differenciated thyroid carcinomas are the most frequently encountered endocrine
      tumours. These hormono-dependent carcinomas have a good prognosis. Data derived
      from molecular biology allowed a better understanding of pathophysiological
      mechanisms involved in tumorigenesis of thyroid papillar and follicular
      carcinomas. The use of the works derived from molecular biology also allowed a
      better diagnostic and therapeutic management of the thyroid cancer patients,
      particularly using recombinant human TSH. Familial thyroid cancer disease must
      also be recognised to optimise the clinical managemet of patients and their
      family.

PMID- 11847035
TI  - [Update on neuro-oncology].
AB  - This paper summarizes the recent advances in the field of neuro-oncology.
      Improvement in the surgical procedures and radiosurgery, correlation between
      genetic alteration and the chemosensitivity of some primary brain tumors,
      definition of optimal therapeutic regimen in primary central nervous system
      lymphoma and better insights in the physiopathology of paraneoplastic syndrome
      represent the most significant contribution in the field over the past three
      years.

PMID- 11847036
TI  - [Update in medical informatics in oncology].
AB  - Through the implementation of the French reform of resources allocation,
      according to the French DRG system (PMSI), all the medical records of French
      hospitals are currently indexed according to the same rules and classifications.
      As a by-product, these discharge summaries are merged into huge administrative
      databases covering both public and private settings. Statistical analysis of
      these data have begun, and seems to be worthwhile in oncology, e.g. for assessing
      the burden of cancer treatments in hospitals, for revealing the regional
      variations in practice or for estimating the incidence of melanoma. However,
      fully anonymous data leading to double counts, questionable quality of summaries
      and lack of complete covering in radiotherapy centres, still impede from using
      the data for epidemiological purpose. Short term improvements are under way:
      changes in quality assessment and control, possibility of linking successive
      stays of a patient while respecting privacy, implementation of new classification
      of procedures and new descriptions of "casemix". The French DRG could then have a
      place in the monitoring of cancer both at national and regional levels.

PMID- 11847037
TI  - Apparently, diffusion coefficient value and stroke treatment remains mysterious.

PMID- 11847038
TI  - Sources of variability in measuring carotid stenosis on time-resolved contrast
      enhanced MR angiograms.

PMID- 11847039
TI  - Acute postischemic renormalization of the apparent diffusion coefficient of water
      is not associated with reversal of astrocytic swelling and neuronal shrinkage in
      rats.
AB  - BACKGROUND AND PURPOSE: Initially decreased apparent diffusion coefficient (ADC)
      values are reversible if reperfusion is rapidly performed after focal brain
      ischemia. We sought to determine if reperfusion-induced renormalization of
      initially abnormal values indicates reversal of cellular, morphologic changes
      that occur during acute ischemia. METHODS: Eighteen rats underwent 30 minutes of
      middle cerebral artery occlusion (MCAO) without reperfusion (group A, n = 6),
      with 1.5 hours of reperfusion (group B, n = 6), or with 12 hours of reperfusion
      (group C, n = 6). Diffusion- and perfusion-weighted MR images were obtained at
      the end of MCAO and 1.5 and 12 hours after reperfusion. Immediately after the
      final MR study, the brains were fixed by cardiac perfusion with 4%
      paraformaldehyde. Neuronal injury was evaluated on hematoxylin-eosin-stained
      slices, and astrocytic size was determined by the area of glial fibrillary acidic
      protein (GFAP) plus S-100 expression. RESULTS: In group A in which ADC values
      decreased significantly, 47 +/-12% of the neurons were slightly shrunken;
      astrocytes were moderately swollen, and the area expressing GFAP plus S-100 was
      larger than that in the contralateral hemisphere (117 microm(2) +/- 6 vs 89
      microm(2) +/- 2; P <.001). In group B in which ADC had renormalized, most neurons
      were moderately shrunken, and the frequency of such neurons was greater in group
      B (92% +/- 2) than in group A (P <.001); astrocytes were markedly swollen, and
      the area was larger than that in the contralateral hemisphere (123 microm(2) +/-
      8 vs 85 microm(2) +/- 4, P <.001). In group C in which a secondary ADC decrease
      occurred, most neurons (94% +/- 3) were severely shrunken, and some had
      eosinophilic cytoplasm; astrocytes were disintegrated, and the area of GFAP plus
      S-100 expression was reduced (78 microm(2) +/- 4 vs 90 microm(2) +/- 5, P <.001).
      CONCLUSION: Reperfusion-induced acute renormalization of ADC values is not
      associated with the reversal of neuronal shrinkage and astrocytic swelling that
      occur during ischemia. Conversely, the morphologic changes of astrocytes and
      neurons progressively worsen over time, although ADC values show a biphasic
      change.

PMID- 11847040
TI  - Prognostic value of subacute crossed cerebellar diaschisis: single-photon
      emission CT study in patients with middle cerebral artery territory infarct.
AB  - BACKGROUND AND PURPOSE: Although chronic-stage crossed cerebellar diaschisis
      (CCD) is reported to be associated with the neurologic state or clinical
      improvement after infarct, the prognostic value of early-stage CCD remains
      controversial. Our aim was to determine whether measurements of CCD in the acute
      and subacute stages obtained at single-photon emission CT (SPECT) facilitate the
      prediction of stroke outcome. METHODS: The pattern of cerebral blood flow changes
      after the occurrence of acute middle cerebral artery ischemia with severe
      cortical symptoms was examined by using technetium 99m-hexamethylpropyleneamine
      oxime ((99m)Tc-HMPAO) SPECT. Fifteen patients (mean age, 73 years +/- 8 [SD])
      with unilateral ischemia were examined in the early subacute stage (10 days +/-
      5). In 11 patients, SPECT was performed in both the acute (16 hours +/- 10) and
      subacute stages. From the total counts obtained from each cerebellar hemisphere,
      the asymmetry index (AI) was calculated as follows: [(value in unaffected
      hemisphere--value in affected hemisphere)/value in unaffected hemisphere] x 100.
      Clinical outcome (at 60 days) was assessed by means of the Scandinavian Stroke
      Scale (SSS) and Barthel Index (BI). RESULTS: AIs in the acute stage and clinical
      outcome (ie, SSS and BI scores) showed no significant correlation, but the
      severity of AI in the early subacute stage correlated significantly with both the
      final SSS (r = -0.69; P <.01) and BI scores (r = -0.82; P <.01). CONCLUSION:
      Cerebellar hypoperfusion detected at (99m)Tc-HMPAO SPECT in the early subacute
      stage in patients with supratentorial infarct indicates a worse clinical outcome.

PMID- 11847041
TI  - Diffusion-weighted MR imaging in normal human brains in various age groups.
AB  - BACKGROUND AND PURPOSE: Few studies have concerned the absolute apparent
      diffusion coefficient (ADC) values in the normal human brain and the effect of
      aging on diffusion. Therefore, our purpose was to determine whether the average
      ADC (ADC(av)) values in the various regions of the brain differ with age, sex, or
      hemisphere and to establish reference values of the absolute ADC(av) for further
      studies. METHODS: Subjects (40 men and 40 women) were chosen from a healthy
      population; age groups were 20-34, 35-49, and 50-64 years and 65 years or older
      (n = 20 each). All subjects were examined with MR imaging, including conventional
      and diffusion-weighted imaging in three orthogonal directions with two b values
      (0 and 1000 s/mm(2)) at 1.5 T. Bilateral ADC(av) values were determined in 36
      regions of interest encompassing the entire brain. RESULTS: ADC(av) values were
      highest in the cortical gray matter ([0.89 +/- 0.04] x 10(-3) mm(2)/s; range,
      0.78-1.09 x 10(-3)), lower in the deep gray matter ([0.75 +/- 0.03] x 10(-3)
      mm(2)/s; range, 0.64-0.83 x 10(-3)), and lowest in the white matter ([0.70 +/-
      0.03] x 10(-3) mm(2)/s; range, 0.62-0.79 x 10(-3)). The ADC(av) values did not
      significantly change with aging, except for an increase in the lateral
      ventricles. No difference was observed between women and men or between the
      hemispheres. CONCLUSION: The data reported herein are representative, and the
      ADC(av) values can be used for reference in future studies and in clinical
      settings.

PMID- 11847042
TI  - Cerebral ischemia detected with diffusion-weighted MR imaging after stent
      implantation in the carotid artery.
AB  - BACKGROUND AND PURPOSE: Concern regarding the safety of stent implantation in the
      carotid artery exists because of the risk of cerebral embolization during the
      procedure. The purpose of this prospective study was to determine the incidence
      of new areas of cerebral ischemia, as detected by using diffusion-weighted MR
      imaging after stent implantation in the carotid artery. METHODS: Diffusion
      weighted MR imaging of the brain was performed in 67 patients with 70 high-grade
      stenoses of the carotid artery before and 24 hours after stent implantation.
      RESULTS: The neurologic status of the patients was unchanged after 69 of 70
      procedures. During one procedure, symptomatic cerebral embolization occurred.
      Diffusion-weighted MR images showed new ipsilateral lesions after stent
      implantation in 20 patients (29%), including the symptomatic patient, and new
      contralateral lesions in six patients (9%). Fifty-two of 59 postprocedural
      lesions occurred in the vascular territory supplied by the treated vessel. The
      occurrence of new postprocedural ipsilateral lesions was not significantly
      correlated with patient demographic data, characteristics of the stenoses, or
      details of the procedure. CONCLUSION: In 29% of the procedures, stent
      implantation in the carotid artery was associated with new areas of cerebral
      ischemia, as detected by using diffusion-weighted MR images; these findings
      indicated the occurrence of cerebral microemboli during such procedures. In all
      patients except one, the new lesions were clinically silent.

PMID- 11847043
TI  - Contrast-enhanced three-dimensional transcranial color-coded sonography of
      intracranial stenoses.
AB  - BACKGROUND AND PURPOSE: Intracranial stenoses are associated with a considerable
      number of strokes each year. The clinical value of a workstation-based three
      dimensional (3D) reconstruction system for transcranial color-coded sonography
      was evaluated in patients with intracranial stenosis or occlusion. METHODS:
      Twenty-six patients (13 men, 13 women; mean age, 57 years +/- 12 [SD]) with 36
      intracranial stenoses or occlusions, as detected at two-dimensional (2D) color
      Doppler imaging (CDI) and digital subtraction angiography (DSA), underwent
      Levovist-enhanced power Doppler imaging (PDI), with subsequent 3D reconstruction.
      A workstation connected to a magnetic sensor capable of spatial localization of
      the probe was used to reconstruct 3D images of the circle of Willis from serial
      PDI images. RESULTS: At DSA, seven (19%) stenoses were estimated to less than
      50%, 24 (67%) were 50% or more, and five (14%) were occluded. DSA and 3D-PDI
      estimates of the degree of stenosis agreed in 33 cases (92%), with a weighted
      kappa value of 0.86. Disagreement occurred with two subtotal basilar artery
      stenoses and one subtotal middle cerebral artery stenosis, which were evaluated
      as being complete occlusions at 3D-PDI. Interobserver agreement between two
      experienced 3D investigators in estimating the percentage of stenosis was high
      (correlation coefficient,.98). CONCLUSION: 3D-PDI enables the investigator to
      reconstruct virtually any arbitrary viewing angle. Compared with conventional
      CDI, 3D-PDI offers easier spatial assessment of intracranial stenoses, and its
      findings are sufficiently correlated with angiographic findings. Because
      different investigators can postprocess the same 3D data, improving
      reproducibility and reducing investigator dependency in transcranial color-coded
      sonography may be possible.

PMID- 11847044
TI  - Contrast-enhanced 3D MR angiography of the carotid artery: comparison with
      conventional digital subtraction angiography.
AB  - BACKGROUND AND PURPOSE: Since 1996, several preliminary studies have shown the
      usefulness of contrast material-enhanced MR angiography for imaging supraaortic
      vessels. The aim of this study was to compare the accuracy of contrast-enhanced
      3D MR angiography with that of digital subtraction angiography (DSA) in the
      evaluation of carotid artery stenosis. METHODS: A blinded comparison of first
      pass contrast-enhanced MR angiography with conventional DSA was performed in 120
      patients (240 arteries). MR angiography was performed with a 1.5-T magnet with
      gradient overdrive equipment, by using a coronal radiofrequency-spoiled 3D fast
      low-angle-shot sequence after the intravenous injection of gadodiamide. The
      guidelines of the North American Symptomatic Carotid Endarterectomy Trial for
      measuring stenosis of the internal carotid artery were applied on maximum
      intensity projection (MIP) images and conventional catheter angiograms. RESULTS:
      Grading of stenoses on MR angiograms agreed with grading of stenoses on DSA
      images in 89% of arteries. In the severe stenosis group (70-99%), agreement was
      93%. All internal carotid occlusions (n = 28) and seven of nine pseudo-occlusions
      were accurately detected with contrast-enhanced MR angiography. The correlation
      between MR angiography and DSA for determination of minimal, moderate, and severe
      stenoses and occlusion was statistically significant (r = 0.91, P<.001).
      CONCLUSIONS: This investigation with a large number of patients confirms that
      contrast-enhanced MR angiography could become a diagnostic alternative to DSA in
      the treatment of patients with carotid artery disease.

PMID- 11847045
TI  - Intracranial meningeal involvement in Churg-Strauss syndrome.
AB  - We describe the case of a 54-year-old woman with a clinical diagnosis of Churg
      Strauss syndrome (CSS). The patient had a fever of unknown origin, severe
      headache, progressing left ophthalmoplegia, and visual acuity disturbance. MR
      imaging revealed diffuse and thick hypointense lesions on T2-weighted images in
      the frontal meninges and anterior falx cerebri with diffuse enhancement. Similar
      lesions were also detected in the left superior ophthalmic fissure to the
      cavernous sinus. Nodular lesions in the fourth ventricle, which might have been
      the cause of hydrocephalus, were hypointense on T2-weighted images. These MR
      imaging findings suggested remote granulomatous involvement in the meninges and
      choroid plexus associated with CSS. To our knowledge, remote meningeal
      involvement in association with CSS has not been previously reported.

PMID- 11847046
TI  - Effects of physiologic human brain motion on proton spectroscopy: quantitative
      analysis and correction with cardiac gating.
AB  - SUMMARY: Proton MR spectroscopy is a powerful noninvasive method that enables
      measurement of certain brain metabolites in healthy subjects and patients with
      diseases. A major difficulty with clinical and research applications of in vivo
      proton MR spectroscopy is the variability of metabolite concentrations,
      especially in regions with substantial physiologic motion. In our preliminary
      evaluation, we tested the hypothesis that physiologic brain motion leads to lower
      mean metabolite concentrations and higher SDs for the measured metabolite
      concentrations.

PMID- 11847048
TI  - Angiotropic large cell lymphoma with imaging characteristics of CNS vasculitis.
AB  - This report documents a case of angiotropic large cell lymphoma (ALCL) with
      imaging characteristics of CNS vasculitis. A 47-year-old man was unresponsive
      after a 5-month progression of neurologic deterioration and intermittent fevers.
      MR imaging revealed multiple areas of abnormally increased T2 signal intensity in
      the cerebral cortex and subcortical white matter. Despite corticosteroid
      treatment for presumed CNS vasculitis, the patient died. Necropsy revealed a
      diffuse intravascular malignant mononuclear proliferation consistent with ALCL.

PMID- 11847047
TI  - Reduced N-acetylaspartate levels in the frontal cortex of 3,4
      methylenedioxymethamphetamine (Ecstasy) users: preliminary results.
AB  - BACKGROUND AND PURPOSE: The perceived safety of the recreational drug
      methylenedioxymethamphetamine (MDMA), or Ecstasy, conflicts with animal evidence
      indicating that MDMA damages cortical serotonin (5-HT) neurons at doses similar
      to those used by humans. Few data are available about the effects of MDMA on the
      human brain. This study was designed to evaluate MDMA-related alterations in
      metabolite ratios with single-voxel proton ((1)H) MR spectroscopy. METHODS:
      Fifteen male MDMA users (mean lifetime exposure, 723 tablets; mean time since
      last tablet, 12.0 weeks) and 12 age-matched control subjects underwent single
      voxel (1)H MR spectroscopy. N-Acetylaspartate (NAA)/creatine (Cr), NAA/Choline
      (Cho), and myoinositol (MI)/Cr ratios were measured in midfrontal gray matter,
      midoccipital gray matter, and right parietal white matter. Data were analyzed
      with linear model-based multivariate analysis of variance. RESULTS: NAA/Cr (P
      =.04) and NAA/Cho (P =.03) ratios, markers associated with neuronal loss or
      dysfunction, were reduced in the frontal cortex of MDMA users. Neither NAA/Cr (P
      =.72) nor NAA/Cho (P =.12) ratios were different between both groups in occipital
      gray matter and parietal white matter (P =.18). Extent of previous MDMA use and
      frontal cortical NAA/Cr (rho = -.50, P =.012) or NAA/Cho (rho = -.550, P <.01)
      ratios were significantly associated. CONCLUSION: Reduced NAA/Cr and NAA/Cho
      ratios at (1)H MR spectroscopy provide evidence for neuronal abnormality in the
      frontal cortex of MDMA users; these are correlated with the degree of MDMA
      exposure. These data suggest that MDMA may be a neurotoxin in humans, as it is in
      animals.

PMID- 11847049
TI  - Astroblastoma: radiologic-pathologic correlation and distinction from ependymoma.
AB  - SUMMARY: Astroblastoma is a rare primary glial tumor with a characteristic
      appearance on neuroradiologic images. Typically, astroblastomas are large,
      lobulated, peripheral, supratentorial, solid, and cystic masses with relatively
      little associated vasogenic edema and tumor infiltration for their large size.
      The solid component of the mass has a bubbly appearance and a T2 signal that is
      isointense to gray matter. Punctate calcifications are often present.
      Neuroradiologists should be familiar with the characteristic appearance of this
      tumor.

PMID- 11847050
TI  - MR imaging characteristics of cranial bone marrow in adult patients with
      underlying systemic disorders compared with healthy control subjects.
AB  - BACKGROUND AND PURPOSE: In young adults, hematopoietic bone marrow has usually
      converted to fatty marrow. Fat hyperintensity on T1-weighted MR images
      facilitates the evaluation of marrow abnormalities. Our purpose was to compare
      cranial marrow signal intensity patterns in adults with systemic disorders and in
      healthy subjects. METHODS: MR images in 25 adults with underlying systemic
      disorders (chronic anemia, lymphoma, leukemia, or other infiltrative processes)
      and 44 healthy aged-matched individuals were retrospectively reviewed. Calvarial
      and clival marrow signal intensity on sagittal T1-weighted images was graded
      relative to that of orbital fat, white matter (WM), and gray matter (GM). Marrow
      was classified as homogeneous (uniformly isointense), diffusely heterogeneous
      (mottled), or focally heterogeneous (generally isointense with a focal lesion).
      RESULTS: In 84% of the control subjects, bone marrow was iso- or hyperintense
      relative to WM. Patients had abnormal diploic (n = 22) or clival (n = 17) marrow;
      22 had calvarial marrow that was hypointense relative to WM compared with that in
      seven healthy subjects (P <.001). Marrow hypointensity relative to WM was a
      sensitive (93%) and specific (86%) marker of pathologic abnormality. Although
      marrow hypointensity relative to GM was specific (96%), it was not sensitive
      (67%). Calvarial and clival marrow patterns, respectively, were homogeneous in
      81% and 64% of control subjects and 76% and 60% of patients. Clival marrow
      intensity varied more than did calvarial intensity; therefore, clival criteria
      were less sensitive and accurate in systemic disease detection. CONCLUSION:
      Homogeneous diploic marrow hypointense relative to WM on non-contrast-enhanced T1
      weighted images suggests an underlying systemic or hematologic disorder and
      requires appropriate clinical correlation and evaluation.

PMID- 11847051
TI  - Temporal lobe morphology in normal aging and traumatic brain injury.
AB  - BACKGROUND AND PURPOSE: Little is known regarding changes in the temporal lobe
      associated with traumatic brain injury (TBI) in early-to-mid adulthood. We report
      on two quantitative MR studies: study 1 addressed age-related changes of the
      temporal lobe in subjects aged 16-72 years; information obtained in this study
      provided a normative database for comparison with findings in 118 patients with
      TBI who were included in study 2. We expected stable morphology in healthy
      subjects and trauma-related atrophy in patients with TBI. METHODS: MR
      multispectral tissue segmentation was used to calculate bilateral temporal lobe
      gyrus and sulcus, sylvian fissure CSF, hippocampus, and temporal horn volumes and
      to measure the white matter (WM) temporal stem. RESULTS: With normal aging, gyral
      volume remained stable, decreasing approximately 0.26% per year (total,
      approximately 11%). Sulcal CSF volume doubled. Hippocampal volume decreased
      (minimally, significantly); temporal horn volume increased (not significantly)
      and was minimally related to hippocampal volume. WM measurements were constant.
      Trauma changed morphology; WM measures decreased. Gyral volumes were not
      different between the groups. In TBI, CSF volume increased significantly, was
      most related to reduced WM measurements, and was relatively independent of gyral
      volume. Temporal horn dilatation was related more to WM atrophy than to
      hippocampal atrophy. In TBI, subarachnoid sulcal and temporal horn CSF volumes
      were most related to WM atrophy, which was relatively independent of gyral
      volume; gyral and hippocampal volumes and WM measures were related to memory
      performance. CONCLUSION: Age-related changes cause minimal temporal lobe gyral,
      hippocampal, temporal horn, and WM atrophy. Only subarachnoid sulcal CSF volume
      changed robustly. Trauma produced disproportionate WM loss associated with
      increased temporal horn and sulcal CSF volumes; it caused substantial hippocampal
      atrophy, which was related to memory impairment. Gyral volume did not decrease,
      although it was related to memory performance.

PMID- 11847052
TI  - Magnetization transfer and diffusion tensor MR imaging of acute disseminated
      encephalomyelitis.
AB  - BACKGROUND AND PURPOSE: Patients with acute disseminated encephalomyelitis (ADEM)
      and multiple sclerosis (MS) have a similar pattern of abnormalities on
      conventional MR images. We used magnetization transfer and diffusion tensor MR
      imaging to quantify normal-appearing brain tissue and cervical cord disease in
      patients with ADEM and to compare findings with those in healthy volunteers and
      patients with MS. METHODS: Brain dual-echo, T1-weighted magnetization transfer,
      and diffusion tensor images were obtained in eight patients with ADEM, in 10
      patients with MS, and in 10 healthy volunteers. Fast short-tau inversion
      recovery, T1-weighted, and magnetization transfer cervical cord images were also
      obtained. We identified lesions on the images and quantified their volumes. We
      performed histogram analysis of the magnetization transfer ratio (MTR) and
      average mean histogram analysis of the diffusivity (D) in normal-appearing brain
      tissue and MTR in the cervical cord. RESULTS: Histogram analysis of normal
      appearing brain tissue in patients with MS showed significantly lower MTRs and
      peak positions and significantly higher D averages compared with those in
      patients with ADEM. Patients with MS had significantly lower MTRs and D peak
      heights and significantly higher average D compared with those in healthy
      volunteers. Between patients with ADEM and control subjects, normal-appearing
      brain tissue MTR and D histogram metrics did not differ significantly. Cervical
      cord MTRs did not differ between control subjects and patients with ADEM, whereas
      the average MTR and histogram peak position was significantly lower in patients
      with MS than in the other groups. CONCLUSION: Outside the acute phase of disease
      and as opposed to what happens in MS, the normal-appearing brain tissue and
      cervical cord in patients with ADEM are spared in the pathologic process.

PMID- 11847053
TI  - Cryptococcal choroid plexitis as a mass lesion: MR imaging and histopathologic
      correlation.
AB  - Cryptococcosis is a relatively common mycotic infection of the CNS caused by a
      ubiquitous saprophytic fungus. We present an unusual case of CNS cryptococcosis
      in an immunocompetent patient. Florid choroid plexitis resulted in the formation
      of intraventricular enhancing mass lesions that filled the ventricles and were
      hyperintense to associated periventricular edema on T2-weighted MR images. We
      also noted lesions corresponding to microcystic, dilated Virchow-Robin spaces in
      the basal ganglia that were characteristic of cryptococcal infection.

PMID- 11847054
TI  - Combined direct percutaneous transluminal angioplasty and low-dose native tissue
      plasminogen activator therapy for acute embolic middle cerebral artery trunk
      occlusion.
AB  - BACKGROUND AND PURPOSE: In embolic middle cerebral artery (MCA) trunk occlusion,
      recanalization with direct percutaneous transluminal angioplasty (PTA) may be
      preferable to time-consuming thrombolysis. However, distal embolization with
      small crushed fragments is a complication of direct PTA. We prospectively
      evaluated combined direct PTA and low-dose native tissue plasminogen activator (t
      PA) therapy for acute embolic MCA trunk occlusion. METHODS: Fifteen patients
      underwent direct PTA. The embolus was successfully crushed in 12, who received
      subsequent native t-PA infusion. Direct PTA was performed with a balloon
      catheter, which was advanced into the occlusion site and inflated several times
      until recanalization was established. After PTA, 7.2 mg of native t-PA in 100 mL
      of isotonic sodium chloride solution was infused for 30 minutes. Neurologic
      status was evaluated at admission and immediately and 1 month after treatment. In
      all patients, follow-up CT was performed within 24 hours and 3-7 days after
      onset, and follow-up MR imaging, 1 month after onset. RESULTS: Direct PTA failed
      to crush the embolus in three of 15 patients; these three had no clinical
      improvement. In 11 of 12 patients, combined therapy was successful, with no
      technical complication. Although no symptomatic intracerebral hemorrhage
      occurred, one patient had a small hematoma. All patients with successful
      recanalization had marked clinical improvement. Although angiograms showed distal
      embolizations in 10, cortical infarctions were confirmed in only three at follow
      up. CONCLUSION: Combined direct PTA and IV low-dose native t-PA therapy may be a
      safe alternative to thrombolytic therapy in some patients with embolic MCA trunk
      occlusion.

PMID- 11847055
TI  - Thromboaspiration in the basilar artery: report of two cases.
AB  - Recanalization of the basilar artery is not always achieved with intraarterial
      fibrinolysis. We report two cases of thromboaspiration in the basilar artery in
      which recanalization with fibrinolysis was successful. Thromboaspiration requires
      favorable anatomy and a fresh nonadhesive clot. It reduces the time for
      recanalization, has no hemorrhagic risk, and may prevent distal clot migration.
      Thromboaspiration may be attempted as an adjunct or alternative to intraarterial
      fibrinolysis for basilar artery recanalization.

PMID- 11847056
TI  - Dynamic CT perfusion imaging with acetazolamide challenge for the preprocedural
      evaluation of a patient with symptomatic middle cerebral artery occlusive
      disease.
AB  - We describe the use of a CT-based method of cerebral perfusion imaging, dynamic
      CT perfusion imaging, for the pre- and postprocedural assessment of cerebral
      blood flow in a patient with symptomatic middle cerebral artery occlusive disease
      who underwent balloon angioplasty with stent placement in the affected artery.
      Dynamic CT perfusion imaging represents a widely available and minimally invasive
      alternative to other available methods of cerebral perfusion imaging.

PMID- 11847057
TI  - Effect of Guglielmi detachable coils on intraaneurysmal flow: experimental study
      in canines.
AB  - BACKGROUND AND PURPOSE: Guglielmi detachable coils (GDCs) are effective in
      preventing rebleeding of ruptured aneurysms. To better understand the mechanism
      underlying this protective effect, we evaluated blood flow in aneurysms and their
      parent arteries before and after GDC coil placement. METHODS: An 0.14-inch
      guidewire containing a combined pressure and thermistor sensor was inserted
      through a microcatheter into both the parent artery and the dome of surgically
      created canine aneurysms. Before and after GDC coil placement, intravascular
      pressures and thermodilution responses where recorded in the parent artery and
      aneurysmal dome during injections of room-temperature isotonic sodium chloride
      solution over 4 seconds (5 mL/s) and 2 seconds (20 mL/s) in the parent artery.
      RESULTS: Before GDC coil placement, similar U-shaped thermodilution curves were
      present in the parent artery and in the dome of the aneurysm. GDC coil placement
      reduced intraaneurysmal flow by 61-99.6% (P <.05), prolonged aneurysmal filling
      and washout (dilution interval increased from 5.16 seconds before coil placement
      to 26.79 seconds after coil placement, P < 0.05), and caused a dissociation of
      pressure and flow (shift epsilon was 0.45 seconds before coil placement versus
      0.56 seconds after coil placement, P <.05). Flow in the parent artery was not
      significantly affected by GDC coil placement in the aneurysm. CONCLUSION: In this
      model, intraaneurysmal blood flow can be evaluated with thermodilution. GDC coil
      placement significantly reduces blood flow in aneurysms.

PMID- 11847058
TI  - Elastase-induced saccular aneurysms in rabbits: a dose-escalation study.
AB  - BACKGROUND AND PURPOSE: Reproducible animal models facilitate preclinical
      assessment of aneurysm therapies. Our purpose was to determine if increased
      elastase doses enlarge aneurysms and parent arteries. METHODS: Rabbit right
      common carotid artery (CCA) aneurysms were created with distal ligation and
      intraluminal elastase incubation. Groups were 1) sham (no elastase, n = 3), 2)
      25% elastase (10 minutes, n = 9), 3) 50% elastase (10 minutes, n = 7), and 4) 50%
      elastase (20 minutes, n = 41). Angiography was performed after 14 days. Resultant
      aneurysm width and height and parent artery diameters were measured and compared
      with the Student t or Mann-Whitney (Wilcoxon rank sum) test. RESULTS: Proximal
      segments were enlarged in all elastase subjects and no sham subjects. Mean
      measurements were significantly smaller in the sham group than in other groups.
      Aneurysm widths and heights, respectively, were 3.8 mm +/- 0.8 and 7.4 mm +/- 2.0
      in the low-dose group; 3.9 mm +/- 1.3 and 8.5 mm +/- 3.8, medium-dose group; and
      4.1 mm +/- 1.1 and 8.7 mm +/- 2.6, high-dose group. Differences were not
      significant. Parent artery widths were 3.5 mm +/- 0.7, 3.8 mm +/- 0.7, and 4.3 mm
      +/- 1.4 in the low-, medium-, and high-dose groups, respectively; the high-dose
      group had larger arteries (P =.07). CONCLUSION: Aneurysms were reliably created
      and were sized similar to human intracranial aneurysms. Elastase concentration
      and incubation duration did not affect resultant size. Relatively short
      incubation (eg, 10 minutes) and 25% elastase can be used to create rabbit
      aneurysms, especially if dilatation of adjacent parent arteries is to be avoided.

PMID- 11847059
TI  - Fast recovery 3D fast spin-echo MR imaging of the inner ear at 3 T.
AB  - High-resolution MR imaging of the inner ear with a heavily T2-weighted 3D fast
      spin-echo sequence has been performed successfully at 1.5 T. However, at 3 T, the
      longer T1 time of CSF necessitates a longer TR, resulting in significantly
      prolonged imaging times. In this study, the fast recovery 3D fast spin-echo
      sequence, which permits the TR to be reduced while maintaining T2 contrast, was
      optimized at 3 T for imaging of the inner ear. The optimized sequence parameters
      are as follows: 1500/294 (TR/TE); echo spacing, 18.1 ms; bandwidth, 38 kHz at 512
      readout; and imaging time, 13 minutes.

PMID- 11847060
TI  - Perineural tumor spread along the auriculotemporal nerve.
AB  - BACKGROUND AND PURPOSE: Evaluation of images of perineural tumor spread in
      patients with head and neck malignancies is essential for planning treatment and
      determining the patient's prognosis. Although the communications between the
      facial and trigeminal nerves are not widely known, they may provide a route for
      tumor growth. The purpose of this study was to elucidate the course of the
      auriculotemporal nerve, as well as the clinical and imaging findings that suggest
      involvement of the communication between the facial nerve and the mandibular
      division (V(3)) of the trigeminal nerve. METHODS: Images in 15 patients with
      clinical or radiologic findings suggestive of perineural tumor spread along the
      auriculotemporal nerve were reviewed. Involvement of the main trunk of the facial
      nerve, auriculotemporal nerve, V(3), trigeminal cistern, and ganglion and
      adjacent anatomic structures were noted in each patient. RESULTS: The course of
      the auriculotemporal nerve was described in detail. More than 50% of patients
      with perineural tumor spread along the auriculotemporal nerve had clinical signs
      of auriculotemporal nerve dysfunction, including periauricular pain and
      temporomandibular joint (TMJ) dysfunction or tenderness. Images in 13 of 15
      patients with such tumor spread demonstrated findings of tumor growth along
      V(3.). CONCLUSION: Knowledge of the course of the auriculotemporal nerve is
      critical in evaluating images for findings of tumor spread along this nerve.
      Periauricular pain, TMJ dysfunction or tenderness, and imaging signs of V(3)
      involvement are important indicators of potential involvement of the
      auriculotemporal nerve.

PMID- 11847061
TI  - Wegener granulomatosis involving the pterygopalatine fossa: an unusual case of
      trigeminal neuropathy.
AB  - We report on a case of Wegener granulomatosis in the pterygopalatine fossa that
      was associated with trigeminal neuropathy. MR and CT examinations were useful in
      depicting the extent of the lesion and suggesting a perineural spread. Diagnosis
      was confirmed with positive serum assay findings for the presence of cytoplasmic
      antineutrophil cytoplasm antibody.

PMID- 11847062
TI  - Multiple myeloma involving the thyroid cartilage: case report.
AB  - Multiple myeloma involving the thyroid cartilage is exceedingly rare. We describe
      a patient with progressive airway obstruction due to diffuse involvement of the
      thyroid cartilage with multiple myeloma. CT revealed a conglomerate of
      calcifications of the thyroid cartilage. Additional classic lytic lesions of
      multiple myeloma were subsequently found in the bones, without associated
      calcifications. Calcified matrix in multiple myeloma involving the thyroid
      cartilage should now be included as an additional manifestation of extraosseous
      multiple myeloma.

PMID- 11847063
TI  - Aneurysmal bone cyst of the orbit.
AB  - Aneurysmal bone cysts of the skull are rare, and orbital involvement of these
      cysts is even less frequent. We present CT, MR imaging, and histopathologic
      findings of an aneurysmal bone cyst of the orbit in a 13-year-old female
      adolescent. The tumor mainly involved the frontal bone. MR imaging findings of
      the aneurysmal bone cyst of the skull were highly suggestive of the diagnosis.

PMID- 11847064
TI  - Neuroimaging in pediatric brain tumors: Gd-DTPA-enhanced, hemodynamic, and
      diffusion MR imaging compared with MR spectroscopic imaging.
AB  - BACKGROUND AND PURPOSE: Gadolinium-enhanced MR images assist in defining tumor
      borders; however, the relation between tumor cell extent and contrast-enhanced
      regions is unclear. Our aim was to improve conventional neuroimaging of pediatric
      brain tumors with hemodynamic, diffusion, and spectroscopic MR imaging. METHODS:
      We performed conventional MR and MR spectroscopic imaging in 31 children with
      neuroglial brain tumors. Hemodynamic MR imaging was performed in 16 patients with
      a first-pass intravenous bolus of gadolinium diethylenetriaminepentaacetic acid
      (Gd-DTPA); apparent diffusion coefficients (ADCs) were measured in 12 patients.
      To account for multiple measurements in a patient, we used a nested analysis of
      variance. RESULTS: At MR spectroscopy, choline (Cho)-containing compounds
      (indicating tumor) and lipid levels (indicating necrosis) did not correlate with
      percent Gd-DTPA enhancement on MR images. Percent enhancement was positively
      correlated with relative cerebral blood volumes (rCBVs) (P =.05) and negatively
      correlated with ADCs (P <.001). Stepwise multiple linear regression revealed that
      rCBV (P =.008), ADC (P =.022), and lipid (P <.001) levels were significant
      independent predictors of percent enhancement. Tumor spectral patterns were
      detected in tumor regions and outside enhancing tumor beds in patients with
      clinical progression; these were confirmed at neuropathologic analysis.
      CONCLUSION: MR spectroscopic imaging improves the assessment of pediatric brain
      tumors by adding biochemical information regarding tumor involvement and by
      depicting residual or recurrent tumor outside the Gd-DTPA-enhanced tumor bed.
      rCBV and ADC mapping complemented MR spectroscopic imaging. We recommend the use
      of MR spectroscopic imaging in addition to conventional MR imaging in assessing
      pediatric brain tumors.

PMID- 11847065
TI  - CT findings in the infantile form of citrullinemia.
AB  - Citrullinemia is a rare autosomal recessive inborn error of the urea cycle due to
      a deficiency in argininosuccinic acid synthetase. We present two cases of the
      infantile form of citrullinemia in which CT revealed bilateral and symmetric
      corticosubcortical hypoattenuating areas, ulegyric changes, and atrophy in the
      frontal lobes, as well as atrophy in the gyrus cinguli, insulae, and temporal
      lobes.

PMID- 11847066
TI  - Depiction of a postoperative pseudomeningocele with digital subtraction
      myelography.
AB  - Digital subtraction myelography is described for its utility in the detection of
      dural leaks associated with pseudomeningoceles. Although myelography, CT, and MR
      imaging have been described as effective means for diagnosing pseudomeningocele,
      this complicated entity can be difficult to diagnose.

PMID- 11847067
TI  - Historical note.

PMID- 11847068
TI  - Perfusion CT scans.

PMID- 11847069
TI  - Beyond the central dogma.

PMID- 11847070
TI  - A Bayesian approach to discriminate between alternative DNA sequence
      segmentations.
AB  - MOTIVATION: As a result of recombination or rate variation, a DNA sequence
      alignment may have a mosaic structure, where different segments correspond to
      different evolutionary histories. While several methods have been developed to
      predict DNA mosaic structures, they do not properly address the question of
      whether the predicted segmentation itself is statistically significant, or
      whether it is significantly better than an alternative mosaic structure predicted
      with another method. The objective of the present article is to devise an
      approximate Bayesian hypothesis test to discriminate between alternative
      candidate mosaic structures. RESULTS: We have applied the proposed discrimination
      scheme to various synthetic and real-world DNA sequence alignments. On the
      synthetic data, the algorithm identified the true mosaic structure in nine out of
      ten cases. On the real-world sequence alignments, it selected the same mosaic
      structures as predicted in the literature.

PMID- 11847071
TI  - A data-mining approach to spacer oligonucleotide typing of Mycobacterium
      tuberculosis.
AB  - MOTIVATION: The Direct Repeat (DR) locus of Mycobacterium tuberculosis is a
      suitable model to study (i) molecular epidemiology and (ii) the evolutionary
      genetics of tuberculosis. This is achieved by a DNA analysis technique
      (genotyping), called sp acer oligo nucleotide typing (spoligotyping ). In this
      paper, we investigated data analysis methods to discover intelligible knowledge
      rules from spoligotyping, that has not yet been applied on such representation.
      This processing was achieved by applying the C4.5 induction algorithm and
      knowledge rules were produced. Finally, a Prototype Selection (PS) procedure was
      applied to eliminate noisy data. This both simplified decision rules, as well as
      the number of spacers to be tested to solve classification tasks. In the second
      part of this paper, the contribution of 25 new additional spacers and the
      knowledge rules inferred were studied from a machine learning point of view. From
      a statistical point of view, the correlations between spacers were analyzed and
      suggested that both negative and positive ones may be related to potential
      structural constraints within the DR locus that may shape its evolution directly
      or indirectly. RESULTS: By generating knowledge rules induced from decision
      trees, it was shown that not only the expert knowledge may be modeled but also
      improved and simplified to solve automatic classification tasks on unknown
      patterns. A practical consequence of this study may be a simplification of the
      spoligotyping technique, resulting in a reduction of the experimental constraints
      and an increase in the number of samples processed.

PMID- 11847072
TI  - Identification of characteristic oligonucleotides in the bacterial 16S ribosomal
      RNA sequence dataset.
AB  - MOTIVATION: The phylogenetic structure of the bacterial world has been
      intensively studied by comparing sequences of 16S ribosomal RNA (16S rRNA). This
      database of sequences is now widely used to design probes for the detection of
      specific bacteria or groups of bacteria one at a time. The success of such
      methods reflects the fact that there are local sequence segments that are highly
      characteristic of particular organisms or groups of organisms. It is not clear,
      however, the extent to which such signature sequences exist in the 16S rRNA
      dataset. A better understanding of the numbers and distribution of highly
      informative oligonucleotide sequences may facilitate the design of hybridization
      arrays that can characterize the phylogenetic position of an unknown organism or
      serve as the basis for the development of novel approaches for use in bacterial
      identification. RESULTS: A computer-based algorithm that characterizes the extent
      to which any individual oligonucleotide sequence in 16S rRNA is characteristic of
      any particular bacterial grouping was developed. A measure of signature quality,
      Q(s), was formulated and subsequently calculated for every individual
      oligonucleotide sequence in the size range of 5-11 nucleotides and for 15mers
      with reference to each cluster and subcluster in a 929 organism representative
      phylogenetic tree. Subsequently, the perfect signature sequences were compared to
      the full set of 7322 sequences to see how common false positives were. The work
      completed here establishes beyond any doubt that highly characteristic
      oligonucleotides exist in the bacterial 16S rRNA sequence dataset in large
      numbers. Over 16,000 15mers were identified that might be useful as signatures.
      Signature oligonucleotides are available for over 80% of the nodes in the
      representative tree.

PMID- 11847074
TI  - Probabilistic Boolean Networks: a rule-based uncertainty model for gene
      regulatory networks.
AB  - MOTIVATION: Our goal is to construct a model for genetic regulatory networks such
      that the model class: (i) incorporates rule-based dependencies between genes;
      (ii) allows the systematic study of global network dynamics; (iii) is able to
      cope with uncertainty, both in the data and the model selection; and (iv) permits
      the quantification of the relative influence and sensitivity of genes in their
      interactions with other genes. RESULTS: We introduce Probabilistic Boolean
      Networks (PBN) that share the appealing rule-based properties of Boolean
      networks, but are robust in the face of uncertainty. We show how the dynamics of
      these networks can be studied in the probabilistic context of Markov chains, with
      standard Boolean networks being special cases. Then, we discuss the relationship
      between PBNs and Bayesian networks--a family of graphical models that explicitly
      represent probabilistic relationships between variables. We show how
      probabilistic dependencies between a gene and its parent genes, constituting the
      basic building blocks of Bayesian networks, can be obtained from PBNs. Finally,
      we present methods for quantifying the influence of genes on other genes, within
      the context of PBNs. Examples illustrating the above concepts are presented
      throughout the paper.

PMID- 11847073
TI  - Adjustments and measures of differential expression for microarray data.
AB  - MOTIVATION: Existing analyses of microarray data often incorporate an obscure
      data normalization procedure applied prior to data analysis. For example, ratios
      of microarray channels intensities are normalized to have common mean over the
      set of genes. We made an attempt to understand the meaning of such procedures
      from the modeling point of view, and to formulate the model assumptions that
      underlie them. Given a considerable diversity of data adjustment procedures, the
      question of their performance, comparison and ranking for various microarray
      experiments was of interest. RESULTS: A two-step statistical procedure is
      proposed: data transformation (adjustment for slide-specific effect) followed by
      a statistical test applied to transformed data. Various methods of analysis for
      differential expression are compared using simulations and real data on colon
      cancer cell lines. We found that robust categorical adjustments outperform the
      ones based on a precisely defined stochastic model, including some commonly used
      procedures.

PMID- 11847075
TI  - Mixture modelling of gene expression data from microarray experiments.
AB  - MOTIVATION: Hierarchical clustering is one of the major analytical tools for gene
      expression data from microarray experiments. A major problem in the
      interpretation of the output from these procedures is assessing the reliability
      of the clustering results. We address this issue by developing a mixture model
      based approach for the analysis of microarray data. Within this framework, we
      present novel algorithms for clustering genes and samples. One of the byproducts
      of our method is a probabilistic measure for the number of true clusters in the
      data. RESULTS: The proposed methods are illustrated by application to microarray
      datasets from two cancer studies; one in which malignant melanoma is profiled
      (Bittner et al., Nature, 406, 536-540, 2000), and the other in which prostate
      cancer is profiled (Dhanasekaran et al., 2001, submitted).

PMID- 11847076
TI  - Inference of a genetic network by a combined approach of cluster analysis and
      graphical Gaussian modeling.
AB  - MOTIVATION: Recent advances in DNA microarray technologies have made it possible
      to measure the expression levels of thousands of genes simultaneously under
      different conditions. The data obtained by microarray analyses are called
      expression profile data. One type of important information underlying the
      expression profile data is the 'genetic network,' that is, the regulatory network
      among genes. Graphical Gaussian Modeling (GGM) is a widely utilized method to
      infer or test relationships among a plural of variables. RESULTS: In this study,
      we developed a method combining the cluster analysis with GGM for the inference
      of the genetic network from the expression profile data. The expression profile
      data of 2467 Saccharomyces cerevisiae genes measured under 79 different
      conditions (Eisen et al., PROC: Natl Acad. Sci. USA, 95, 14683-14868, 1998) were
      used for this study. At first, the 2467 genes were classified into 34 clusters by
      a cluster analysis, as a preprocessing for GGM. Then, the expression levels of
      the genes in each cluster were averaged for each condition. The averaged
      expression profile data of 34 clusters were subjected to GGM, and a partial
      correlation coefficient matrix was obtained as a model of the genetic network of
      S. cerevisiae. The accuracy of the inferred network was examined by the agreement
      of our results with the cumulative results of experimental studies.

PMID- 11847077
TI  - Extensive feature detection of N-terminal protein sorting signals.
AB  - MOTIVATION: The prediction of localization sites of various proteins is an
      important and challenging problem in the field of molecular biology. TargetP, by
      Emanuelsson et al. (J. Mol. Biol., 300, 1005-1016, 2000) is a neural network
      based system which is currently the best predictor in the literature for N
      terminal sorting signals. One drawback of neural networks, however, is that it is
      generally difficult to understand and interpret how and why they make such
      predictions. In this paper, we aim to generate simple and interpretable rules as
      predictors, and still achieve a practical prediction accuracy. We adopt an
      approach which consists of an extensive search for simple rules and various
      attributes which is partially guided by human intuition. RESULTS: We have
      succeeded in finding rules whose prediction accuracies come close to that of
      TargetP, while still retaining a very simple and interpretable form. We also
      discuss and interpret the discovered rules.

PMID- 11847078
TI  - Predicting reliable regions in protein sequence alignments.
AB  - MOTIVATION: Protein sequence alignments have a myriad of applications in
      bioinformatics, including secondary and tertiary structure prediction, homology
      modeling, and phylogeny. Unfortunately, all alignment methods make mistakes, and
      mistakes in alignments often yield mistakes in their application. Thus, a method
      to identify and remove suspect alignment positions could benefit many areas in
      protein sequence analysis. RESULTS: We tested four predictors of alignment
      position reliability, including near-optimal alignment information, column score,
      and secondary structural information. We validated each predictor against a large
      library of alignments, removing positions predicted as unreliable. Near-optimal
      alignment information was the best predictor, removing 70% of the substantially
      misaligned positions and 58% of the over-aligned positions, while retaining 86%
      of those aligned accurately.

PMID- 11847079
TI  - Models@Home: distributed computing in bioinformatics using a screensaver based
      approach.
AB  - MOTIVATION: Due to the steadily growing computational demands in bioinformatics
      and related scientific disciplines, one is forced to make optimal use of the
      available resources. A straightforward solution is to build a network of idle
      computers and let each of them work on a small piece of a scientific challenge,
      as done by Seti@Home (http://setiathome.berkeley.edu), the world's largest
      distributed computing project. RESULTS: We developed a generally applicable
      distributed computing solution that uses a screensaver system similar to
      Seti@Home. The software exploits the coarse-grained nature of typical
      bioinformatics projects. Three major considerations for the design were: (1)
      often, many different programs are needed, while the time is lacking to
      parallelize them. Models@Home can run any program in parallel without
      modifications to the source code; (2) in contrast to the Seti project,
      bioinformatics applications are normally more sensitive to lost jobs. Models@Home
      therefore includes stringent control over job scheduling; (3) to allow use in
      heterogeneous environments, Linux and Windows based workstations can be combined
      with dedicated PCs to build a homogeneous cluster. We present three practical
      applications of Models@Home, running the modeling programs WHAT IF and YASARA on
      30 PCs: force field parameterization, molecular dynamics docking, and database
      maintenance.

PMID- 11847080
TI  - A cluster validity framework for genome expression data.
AB  - This paper presents a method for the assessment of expression cluster validity.

PMID- 11847081
TI  - Avoiding cross hybridization by choosing nonredundant targets on cDNA arrays.
AB  - PROBEWIZ designs PCR primers for amplifying probes for cDNA arrays. The probes
      are designed to have minimal homology to other expressed sequences from a given
      organism. The primer selection is based on user-defined penalties for homology,
      primer quality, and proximity to the 3' end.

PMID- 11847082
TI  - DRAGON View: information visualization for annotated microarray data.
AB  - The DRAGON View information visualization tools aid in the comprehensive analysis
      of large-scale gene expression data that has been annotated with biologically
      relevant information through the generation of three types of complementary
      graphical outputs.

PMID- 11847083
TI  - Tclass: tumor classification system based on gene expression profile.
AB  - A method that incorporates feature selection into Fisher's linear discriminant
      analysis for gene expression based tumor classification and a corresponding
      program Tclass were developed. The proposed method was applied to a public gene
      expression data set for colon cancer that consists of 22 normal and 40 tumor
      colon tissue samples to evaluate its performance for classification. Preliminary
      results demonstrated that using only a subset of genes ranging from 3 to 10 can
      achieve high classification accuracy.

PMID- 11847084
TI  - CGO: utilizing and integrating gene expression microarray data in clinical
      research and data management.
AB  - Clinical GeneOrganizer (CGO) is a novel windows-based archiving, organization and
      data mining software for the integration of gene expression profiling in clinical
      medicine. The program implements various user-friendly tools and extracts data
      for further statistical analysis. This software was written for Affymetrix
      GeneChip *.txt files, but can also be used for any other microarray-derived data.
      The MS-SQL server version acts as a data mart and links microarray data with
      clinical parameters of any other existing database and therefore represents a
      valuable tool for combining gene expression analysis and clinical disease
      characteristics.

PMID- 11847085
TI  - ISEApeaks: an Excel platform for GeneScan and Immunoscope data retrieval,
      management and analysis.
AB  - ISEApeaks retrieves and handles DNA sequencer raw data (peak area and nucleotidic
      length). This Macintosh package efficiently interfaces GeneScan and Immunoscope
      softwares to Excel by extracting data from scattered files, organizing data and
      gathering it into a unique peak database for all samples.

PMID- 11847086
TI  - INCLUSive: integrated clustering, upstream sequence retrieval and motif sampling.
AB  - INCLUSive allows automatic multistep analysis of microarray data (clustering and
      motif finding). The clustering algorithm (adaptive quality-based clustering)
      groups together genes with highly similar expression profiles. The upstream
      sequences of the genes belonging to a cluster are automatically retrieved from
      GenBank and can be fed directly into Motif Sampler, a Gibbs sampling algorithm
      that retrieves statistically over-represented motifs in sets of sequences, in
      this case upstream regions of co-expressed genes.

PMID- 11847087
TI  - PROMO: detection of known transcription regulatory elements using species
      tailored searches.
AB  - We have developed a set of tools to construct positional weight matrices from
      known transcription factor binding sites in a species or taxon-specific manner,
      and to search for matches in DNA sequences.

PMID- 11847088
TI  - GenomePixelizer--a visualization program for comparative genomics within and
      between species.
AB  - GenomePixelizer is a visualization tool that generates custom images of the
      physical or genetic positions of specified sets of genes in whole genomes or
      parts of genomes. Multiple sets of genes can be shown simultaneously with user
      defined characteristics displayed. It allows the analysis of duplication events
      within and between species based on sequence similarities. The program is written
      in Tcl/Tk and works on any platform that supports the Tcl/Tk toolkit.
      GenomePixelizer generates HTML ImageMap tags for each gene in the image allowing
      links to databases. Images can be saved and presented on web pages.

PMID- 11847089
TI  - Generating samples under a Wright-Fisher neutral model of genetic variation.
AB  - A Monte Carlo computer program is available to generate samples drawn from a
      population evolving according to a Wright-Fisher neutral model. The program
      assumes an infinite-sites model of mutation, and allows recombination, gene
      conversion, symmetric migration among subpopulations, and a variety of
      demographic histories. The samples produced can be used to investigate the
      sampling properties of any sample statistic under these neutral models.

PMID- 11847090
TI  - QTL Express: mapping quantitative trait loci in simple and complex pedigrees.
AB  - QTL Express is the first application for Quantitative Trait Locus (QTL) mapping
      in outbred populations with a web-based user interface. User input of three files
      containing a marker map, trait data and marker genotypes allows mapping of single
      or multiple QTL by the regression approach, with the option to perform
      permutation or bootstrap tests.

PMID- 11847091
TI  - PATRI-paternity inference using genetic data.
AB  - PATRI is a new application for paternity analysis using genetic data that
      accounts for the sampling fraction of potential fathers.

PMID- 11847092
TI  - Translation initiation start prediction in human cDNAs with high accuracy.
AB  - MOTIVATION: Correct identification of the Translation Initiation Start (TIS) in
      cDNA sequences is an important issue for genome annotation. The aim of this work
      is to improve upon current methods and provide a performance guaranteed
      prediction. METHODS: This is achieved by using two modules, one sensitive to the
      conserved motif and the other sensitive to the coding/non-coding potential around
      the start codon. Both modules are based on Artificial Neural Networks (ANNs). By
      applying the simplified method of the ribosome scanning model, the algorithm
      starts a linear search at the beginning of the coding ORF and stops once the
      combination of the two modules predicts a positive score. RESULTS: According to
      the results of the test group, 94% of the TIS were correctly predicted. A
      confident decision is obtained through the use of the Las Vegas algorithm idea.
      The incorporation of this algorithm leads to a highly accurate recognition of the
      TIS in human cDNAs for 60% of the cases. AVAILABILITY: The program is available
      upon request from the author.

PMID- 11847093
TI  - Exploring the pathway structure of metabolism: decomposition into subnetworks and
      application to Mycoplasma pneumoniae.
AB  - MOTIVATION: Reconstructing and analyzing the metabolic map of microorganisms is
      an important challenge in bioinformatics. Pathway analysis of large metabolic
      networks meets with the problem of combinatorial explosion of pathways.
      Therefore, appropriate algorithms for an automated decomposition of these
      networks into smaller subsystems are needed. RESULTS: A decomposition algorithm
      for metabolic networks based on the local connectivity of metabolites is
      presented. Interrelations of this algorithm with alternative methods proposed in
      the literature and the theory of small world networks are discussed. The
      applicability of our method is illustrated by an analysis of the metabolism of
      Mycoplasma pneumoniae, which is an organism of considerable medical interest. The
      decomposition gives rise to 19 subnetworks. Three of these are here discussed in
      biochemical terms: arginine degradation, the tetrahydrofolate system, and
      nucleotide metabolism. The interrelations of pathway analysis of biochemical
      networks with Petri net theory are outlined.

PMID- 11847094
TI  - Structure motif discovery and mining the PDB.
AB  - MOTIVATION: Many of the most interesting functional and evolutionary
      relationships among proteins are so ancient that they cannot be reliably detected
      through sequence analysis and are apparent only through a comparison of the
      tertiary structures. The conserved features can often be described as structural
      motifs consisting of a few single residues or Secondary Structure (SS) elements.
      Confidence in such motifs is greatly boosted when they are found in more than a
      pair of proteins. RESULTS: We describe an algorithm for the automatic discovery
      of recurring patterns in protein structures. The patterns consist of individual
      residues having a defined order along the protein's backbone that come close
      together in the structure and whose spatial conformations are similar. The
      residues in a pattern need not be close in the protein's sequence. The work
      described in this paper builds on an earlier reported algorithm for motif
      discovery. This paper describes a significant improvement of the algorithm which
      makes it very efficient. The improved efficiency allows us to use it for doing
      unsupervised learning of patterns occurring in small subsets in a large set of
      structures, a non-redundant subset of the Protein Data Bank (PDB) database of all
      known protein structures.

PMID- 11847095
TI  - The EBI SRS server--recent developments.
AB  - MOTIVATION: The current data explosion is intractable without advanced data
      management systems. The numerous data sets become really useful when they are
      interconnected under a uniform interface--representing the domain knowledge. The
      SRS has become an integration system for both data retrieval and applications for
      data analysis. It provides capabilities to search multiple databases by shared
      attributes and to query across databases fast and efficiently. RESULTS: Here we
      present recent developments at the EBI SRS server (http://srs.ebi.ac.uk). The EBI
      SRS server contains today more than 130 biological databases and integrates more
      than 10 applications. It is a central resource for molecular biology data as well
      as a reference server for the latest developments in data integration. One of the
      latest additions to the EBI SRS server is the InterPro database-Integrated
      Resource of Protein Domains and Functional Sites. Distributed in XML format it
      became a turning point in low level XML-SRS integration. We present InterProScan
      as an example of data analysis applications, describe some advanced features of
      SRS6, and introduce the SRSQuickSearch JavaScript interfaces to SRS.

PMID- 11847096
TI  - Interactive InterPro-based comparisons of proteins in whole genomes.
AB  - MOTIVATION: The SWISS-PROT group at the EBI has developed the Proteome Analysis
      Database utilizing existing resources and providing comprehensive and integrated
      comparative analysis of the predicted protein coding sequences of the complete
      genomes of bacteria, archaea and eukaryotes. The Proteome Analysis Database is
      accompanied by a program that has been designed to carry out interactive InterPro
      proteome comparisons for any one proteome against any other one or more of the
      proteomes in the database.

PMID- 11847097
TI  - Aurora-A overexpression reveals tetraploidization as a major route to centrosome
      amplification in p53-/- cells.
AB  - Aberrations in centrosome numbers have long been implicated in aneuploidy and
      tumorigenesis, but their origins are unknown. Here we have examined how
      overexpression of Aurora-A kinase causes centrosome amplification in cultured
      cells. We show that excess Aurora-A does not deregulate centrosome duplication
      but gives rise to extra centrosomes through defects in cell division and
      consequent tetraploidization. Over expression of other mitotic kinases (Polo-like
      kinase 1 and Aurora-B) also causes multinucleation and concomitant increases in
      centrosome numbers. Absence of a p53 checkpoint exacerbates this phenotype,
      providing a plausible explanation for the centrosome amplification typical of p53
      /- cells. We propose that errors during cell division, combined with the
      inability to detect the resulting hyperploidy, constitute a major cause for
      numerical centrosome aberrations in tumors.

PMID- 11847098
TI  - Regulation of receptor protein-tyrosine phosphatase alpha by oxidative stress.
AB  - The presence of two protein-tyrosine phosphatase (PTP) domains is a striking
      feature in most transmembrane receptor PTPs (RPTPs). The function of the
      generally inactive membrane-distal PTP domain (RPTP-D2) is unknown. Here we
      report that an intramolecular interaction between the spacer region (Sp) and the
      C-terminus in RPTPalpha prohibited intermolecular interactions. Interestingly,
      stress factors such as H(2)O(2), UV and heat shock induced reversible, free
      radical-dependent, intermolecular interactions between RPTPalpha and RPTPalpha
      SpD2, suggesting an inducible switch in conformation and binding. The catalytic
      site cysteine of RPTPalpha-SpD2, Cys723, was required for the H(2)O(2) effect on
      RPTPalpha. H(2)O(2) induced a rapid, reversible, Cys723-dependent conformational
      change in vivo, as detected by fluorescence resonance energy transfer, with cyan
      fluorescent protein (CFP) and yellow fluorescent protein (YFP) flanking RPTPalpha
      SpD2 in a single chimeric protein. Importantly, H(2)O(2) treatment stabilized
      RPTPalpha dimers, resulting in inactivation. We propose a model in which
      oxidative stress induces a conformational change in RPTPalpha-D2, leading to
      stabilization of RPTPalpha dimers, and thus to inhibition of RPTPalpha activity.

PMID- 11847099
TI  - Tyrosine sulfation is required for agonist recognition by glycoprotein hormone
      receptors.
AB  - The glycoprotein hormone receptors (thyrotrophin receptor, TSHr; luteinizing
      hormone/chorionic gonadotrophin receptor, LH/CGr; follicle-stimulating hormone
      receptor, FSHr) constitute a subfamily of rhodopsin-like G protein-coupled
      receptors (GPCRs) with a long N-terminal extracellular extension responsible for
      high-affinity hormone binding. These ectodomains contain two cysteine clusters
      flanking nine leucine-rich repeats (LRR), a motif found in several protein
      families involved in protein-protein interactions. Similar to the situation
      described recently in CCR5, we demonstrate here that the TSHr, as it is present
      at the cell surface, is sulfated on tyrosines in a motif located downstream of
      the C-terminal cysteine cluster. Sulfation of one of the two tyrosines in the
      motif is mandatory for high-affinity binding of TSH and activation of the
      receptor. Site-directed mutagenesis experiments indicate that the motif, which is
      conserved in all members of the glycoprotein hormone receptor family, seems to
      play a similar role in the LH/CG and FSH receptors.

PMID- 11847100
TI  - c-Abl is an effector of Src for growth factor-induced c-myc expression and DNA
      synthesis.
AB  - The mechanism by which the ubiquitously expressed Src family kinases regulate
      mitogenesis is not well understood. Here we report that cytoplasmic tyrosine
      kinase c-Abl is an important effector of c-Src for PDGF- and serum-induced DNA
      synthesis. Inactivation of cytoplasmic c-Abl by the kinase-inactive Abl-PP-K(-)
      (AblP242E/P249E/K290M) or by microinjection of Abl neutralizing antibodies
      inhibited mitogenesis. The kinase-inactive SrcK295M induced a G(1) block that was
      overcome by the constitutively active Abl-PP (AblP242E/P249E). Conversely, the
      inhibitory effect of Abl-PP-K(-) was not compensated by Src. c-Src-induced c-Abl
      activation involves phosphorylation of Y245 and Y412, two residues required for c
      Abl mitogenic function. Finally, we found that p53 inactivation and c-myc
      expression, two cell cycle events regulated by Src during mitogenesis, also
      implied c-Abl: c-Abl function was dispensable in cells deficient in active p53
      and inhibition of c-Abl reduced mitogen-induced c-myc expression. These data
      identify a novel function of cytoplasmic c-Abl in the signalling pathways
      regulating growth factor-induced c-myc expression and we propose the existence of
      a tyrosine kinase signalling cascade (PDGFR/c-Src/c-Abl) important for
      mitogenesis.

PMID- 11847101
TI  - The PreS2 activator MHBs(t) of hepatitis B virus activates c-raf-1/Erk2 signaling
      in transgenic mice.
AB  - The large hepatitis B virus (HBV) surface protein (LHBs) and C-terminally
      truncated middle size surface proteins (MHBs(t)) form the family of the PreS2
      activator proteins of HBV. Their transcriptional activator function is based on
      the cytoplasmic orientation of the PreS2 domain. MHBs(t) activators are
      paradigmatic for this class of activators. Here we report that MHBs(t) is protein
      kinase C (PKC)-dependently phosphorylated at Ser28. The integrity of the
      phosphorylation site is essential for the activator function. MHBs(t) triggers
      PKC-dependent activation of c-Raf-1/Erk2 signaling that is a prerequisite for
      MHBs(t)-dependent activation of AP-1 and NF-kappaB. To analyze the
      pathophysiological relevance of these data in vivo, transgenic mice were
      established that produce the PreS2 activator MHBs(t) specifically in the liver.
      In these mice, a permanent PreS2-dependent specific activation of c-Raf-1/Erk2
      signaling was observed, resulting in an increased hepatocyte proliferation rate.
      In transgenics older than 15 months, an increased incidence of liver tumors
      occurs. These data suggest that PreS2 activators LHBs and MHBs(t) exert a tumor
      promoter-like function by activation of key enzymes of proliferation control.

PMID- 11847102
TI  - Membrane sequestration of the signal transduction protein GlnK by the ammonium
      transporter AmtB.
AB  - The Amt proteins are ammonium transporters that are conserved throughout all
      domains of life, being found in bacteria, archaea and eukarya. In bacteria and
      archaea, the Amt structural genes (amtB) are invariably linked to glnK, which
      encodes a member of the P(II) signal transduction protein family, proteins that
      regulate enzyme activity and gene expression in response to the intracellular
      nitrogen status. We have now shown that in Escherichia coli and Azotobacter
      vinelandii, GlnK binds to the membrane in an AmtB-dependent manner and that GlnK
      acts as a negative regulator of the transport activity of AmtB. Membrane binding
      is dependent on the uridylylation state of GlnK and is modulated according to the
      cellular nitrogen status such that it is maximal in nitrogen-sufficient
      situations. The membrane sequestration of GlnK by AmtB represents a novel form of
      signal transduction in which an integral membrane transport protein functions to
      link the extracellular ammonium concentration to the intracellular responses to
      nitrogen status. The results also offer new insights into the evolution of P(II)
      proteins and a rationale for their trigonal symmetry.

PMID- 11847103
TI  - Calcineurin is essential for survival during membrane stress in Candida albicans.
AB  - The immunosuppressants cyclosporin A (CsA) and FK506 inhibit the protein
      phosphatase calcineurin and block T-cell activation and transplant rejection.
      Calcineurin is conserved in microorganisms and plays a general role in stress
      survival. CsA and FK506 are toxic to several fungi, but the common human fungal
      pathogen Candida albicans is resistant. However, combination of either CsA or
      FK506 with the antifungal drug fluconazole that perturbs synthesis of the
      membrane lipid ergosterol results in potent, synergistic fungicidal activity.
      Here we show that the C.albicans FK506 binding protein FKBP12 homolog is required
      for FK506 synergistic action with fluconazole. A mutation in the calcineurin B
      regulatory subunit that confers dominant FK506 resistance (CNB1-1/CNB1) abolished
      FK506-fluconazole synergism. Candida albicans mutants lacking calcineurin B
      (cnb1/cnb1) were found to be viable and markedly hypersensitive to fluconazole or
      membrane perturbation with SDS. FK506 was synergistic with fluconazole against
      azole-resistant C.albicans mutants, against other Candida species, or when
      combined with different azoles. We propose that calcineurin is part of a membrane
      stress survival pathway that could be targeted for therapy.

PMID- 11847104
TI  - Distinct mechanisms of internalization of Neisseria gonorrhoeae by members of the
      CEACAM receptor family involving Rac1- and Cdc42-dependent and -independent
      pathways.
AB  - Opa adhesins of pathogenic Neisseria species target four members of the human
      carcinoembryonic antigen-related cellular adhesion molecule (CEACAM) family.
      CEACAM receptors mediate opsonization-independent phagocytosis of Neisseria
      gonorrhoeae by human granulocytes and each receptor individually can mediate
      gonococcal invasion of epithelial cells. We show here that gonococcal
      internalization occurs by distinct mechanisms depending on the CEACAM receptor
      expressed. For the invasion of epithelial cell lines via CEACAM1 and CEACAM6, a
      pathogen-directed reorganization of the actin cytoskeleton is not required. In
      marked contrast, ligation of CEACAM3 triggers a dramatic but localized
      reorganization of the host cell surface leading to highly efficient engulfment of
      bacteria in a process regulated by the small GTPases Rac1 and Cdc42, but not Rho.
      Two tyrosine residues of a cytoplasmic immune receptor tyrosine-based activating
      motif of CEACAM3 are essential for the induction of phagocytic actin structures
      and subsequent gonococcal internalization. The granulocyte-specific CEACAM3
      receptor has properties of a single chain phagocytic receptor and may thus
      contribute to innate immunity by the elimination of Neisseria and other CEACAM
      binding pathogens that colonize human mucosal surfaces.

PMID- 11847105
TI  - Conserved properties of hydrogenosomal and mitochondrial ADP/ATP carriers: a
      common origin for both organelles.
AB  - Mitochondria are one of the hallmarks of eukaryotic cells, exporting ATP in
      exchange for cytosolic ADP using ADP/ATP carriers (AAC) located in the inner
      mitochondrial membrane. In contrast, several evolutionarily important anaerobic
      eukaryotes lack mitochondria but contain hydrogenosomes, peculiar organelles of
      controversial ancestry that also supply ATP but, like some fermentative bacteria,
      make molecular hydrogen in the process. We have now identified genes from two
      species of the hydrogenosome-containing fungus Neocallimastix that have three
      fold sequence repeats and signature motifs that, along with phylogenetic
      analysis, identify them as AACs. When expressed in a mitochondrial AAC- deficient
      yeast strain, the hydrogenosomal protein was correctly targeted to the yeast
      mitochondria inner membrane and yielded mitochondria able to perform ADP/ATP
      exchange. Characteristic inhibitors of mitochondrial AACs blocked adenine
      nucleotide exchange by the Neocallimastix protein. Thus, our data demonstrate
      that fungal hydrogenosomes and yeast mitochondria use the same pathway for
      ADP/ATP exchange. These experiments provide some of the strongest evidence yet
      that yeast mitochondria and Neocallimastix hydrogenosomes are but two
      manifestations of the same fundamental organelle.

PMID- 11847106
TI  - Activation of system L heterodimeric amino acid exchangers by intracellular
      substrates.
AB  - System L-type transport of large neutral amino acids is mediated by ubiquitous
      LAT1-4F2hc and epithelial LAT2-4F2hc. These heterodimers are thought to function
      as obligatory exchangers, but only influx properties have been studied in some
      detail up until now. Here we measured their intracellular substrate selectivity,
      affinity and exchange stoichiometry using the Xenopus oocyte expression system.
      Quantification of amino acid influx and efflux by HPLC demonstrated an obligatory
      amino acid exchange with 1:1 stoichiometry. Strong, differential trans
      stimulations of amino acid influx by injected amino acids showed that the
      intracellular substrate availability limits the transport rate and that the
      efflux selectivity range resembles that of influx. Compared with high
      extracellular apparent affinities, LAT1- and LAT2-4F2hc displayed much lower
      intracellular apparent affinities (apparent K(m) in the millimolar range). Thus,
      the two system L amino acid transporters that are implicated in cell growth (LAT1
      4F2hc) and transcellular transport (LAT2-4F2hc) are obligatory exchangers with
      relatively symmetrical substrate selectivities but strongly asymmetrical
      substrate affinities such that the intracellular amino acid concentration
      controls their activity.

PMID- 11847107
TI  - IgG transcytosis and recycling by FcRn expressed in MDCK cells reveals ligand
      induced redistribution.
AB  - The neonatal Fc receptor (FcRn) transports IgG across epithelial cells and
      recycles serum IgG. FcRn binds IgG at the acidic pH of endosomes and releases IgG
      at the basic pH of blood. We expressed rat FcRn in polarized MDCK cells and
      demonstrated that it functions in transcytosis and recycling of IgG. In the
      absence of IgG, FcRn is distributed predominantly apically, but redistributes to
      basolateral locations upon IgG addition, indicating that ligand binding induces a
      signal that stimulates transcytosis. FcRn transcytoses IgG more efficiently in
      the apical to basolateral than the reverse direction when IgG is internalized by
      receptor-mediated endocytosis at acidic pH or by fluid phase endocytosis at basic
      pH. The PI 3-kinase inhibitor wortmannin disrupts basolateral recycling and
      transcytosis in both directions, but only minimally reduces apical recycling.
      Confocal imaging and quantitative IgG transport studies demonstrate that apically
      internalized IgG recycles to the apical surface mainly from wortmannin
      insensitive apical early endosomes, whereas FcRn-IgG complexes that transcytose
      to the basolateral surface pass through downstream Rab11-positive apical
      recycling endosomes and transferrin-positive common endosomal compartments.

PMID- 11847108
TI  - Dynamin and clathrin are required for the biogenesis of a distinct class of
      secretory vesicles in yeast.
AB  - Yeast produce two classes of secretory vesicles (SVs) that differ in both density
      and cargo protein content. In late-acting secretory mutants (e.g. snc1(ala43) and
      sec6-4), both low- (LDSV) and high-density (HDSV) classes of vesicles accumulate
      at restrictive temperatures. Here, we have found that disruptions in the genes
      encoding a dynamin-related protein (VPS1) or clathrin heavy chain (CHC1) abolish
      HDSV production, yielding LDSVs that contain all secreted cargos. Interestingly,
      disruption of the PEP12 gene, which encodes the t-SNARE that mediates all Golgi
      to pre-vacuolar compartment (PVC) transport, also abolishes HDSV production. In
      contrast, deletions in genes that selectively confer vacuolar hydrolase sorting
      to the PVC or protein transport to the vacuole (i.e. VPS34 and VAM3,
      respectively) have no effect. Thus, one branch of the secretory pathway in yeast
      involves an intermediate sorting compartment and has a specific requirement for
      clathrin and a dynamin-related protein in SV biogenesis.

PMID- 11847109
TI  - Role of the ubiquitin-selective CDC48(UFD1/NPL4 )chaperone (segregase) in ERAD of
      OLE1 and other substrates.
AB  - The OLE pathway of yeast regulates the abundance of the ER-bound enzyme Delta-9
      fatty acid desaturase OLE1, thereby controlling unsaturated fatty acid pools and
      membrane fluidity. Previously, we showed that this pathway is exquisitely
      regulated by the ubiquitin/proteasome system. Activation of the pathway involves
      proteasomal processing of a membrane-bound transcription factor and the
      subsequent mobilization of the cleaved, ubiquitylated transcription factor from
      its partner molecule by CDC48(UFD1/NPL4), a ubiquitin-selective chaperone-like
      enzyme. Here we report that the OLE1 protein itself is naturally short-lived and
      is degraded by ubiquitin/proteasome-dependent ER-associated degradation (ERAD).
      We found that CDC48(UFD1/NPL4) plays a second role in the OLE pathway by
      mediating ERAD of OLE1. Intriguingly, other ERAD substrates also require
      CDC48(UFD1/NPL4) for degradation, indicating that this enzyme is a novel,
      constitutive component of the ERAD machinery. We propose that CDC48(UFD1/NPL4)
      functions as a segregase that liberates ubiquitylated proteins from non-modified
      partners.

PMID- 11847110
TI  - Ca(2+) dynamics in the lumen of the endoplasmic reticulum in sensory neurons:
      direct visualization of Ca(2+)-induced Ca(2+) release triggered by physiological
      Ca(2+) entry.
AB  - In cultured rat dorsal root ganglia neurons, we measured membrane currents, using
      the patch-clamp whole-cell technique, and the concentrations of free Ca(2+) in
      the cytosol ([Ca(2+)](i)) and in the lumen of the endoplasmic reticulum (ER)
      ([Ca(2+)](L)), using high- (Fluo-3) and low- (Mag-Fura-2) affinity Ca(2+)
      sensitive fluorescent probes and video imaging. Resting [Ca(2+)](L) concentration
      varied between 60 and 270 microM. Activation of ryanodine receptors by caffeine
      triggered a rapid fall in [Ca(2+)](L) levels, which amounted to only 40--50% of
      the resting [Ca(2+)](L) value. Using electrophysiological depolarization, we
      directly demonstrate the process of Ca(2+)-induced Ca(2+) release triggered by
      Ca(2+) entry through voltage-gated Ca(2+) channels. The amplitude of Ca(2+)
      release from the ER lumen was linearly dependent on I(Ca).

PMID- 11847111
TI  - TNFalpha inhibits skeletal myogenesis through a PW1-dependent pathway by
      recruitment of caspase pathways.
AB  - Cachexia is associated with poor prognosis in patients with chronic disease.
      Tumor necrosis factor-alpha (TNFalpha) plays a pivotal role in mediating cachexia
      and has been demonstrated to inhibit skeletal muscle differentiation in vitro. It
      has been proposed that TNFalpha-mediated activation of NFkappaB leads to down
      regulation of MyoD, however the mechanisms underlying TNFalpha effects on
      skeletal muscle remain poorly understood. We report here a novel pathway by which
      TNFalpha inhibits muscle differentiation through activation of caspases in the
      absence of apoptosis. TNFalpha-mediated caspase activation and block of
      differentiation are dependent upon the expression of PW1, but occur independently
      of NFkappaB activation. PW1 has been implicated previously in p53-mediated cell
      death and can induce bax translocation to the mitochondria. We show that bax
      deficient myoblasts do not activate caspases and differentiate in the presence of
      TNFalpha, highlighting a role for bax-dependent caspase activation in mediating
      TNFalpha effects. Taken together, our data reveal that TNFalpha inhibits
      myogenesis by recruiting components of apoptotic pathways through PW1.

PMID- 11847112
TI  - CD40 is expressed and functional on neuronal cells.
AB  - We show here that CD40 mRNA and protein are expressed by neuronal cells, and are
      increased in differentiated versus undifferentiated N2a and PC12 cells as
      measured by RT-PCR, western blotting and immunofluorescence staining.
      Additionally, immunohistochemistry reveals that neurons from adult mouse and
      human brain also express CD40 in situ. CD40 ligation results in a time-dependent
      increase in p44/42 MAPK activation in neuronal cells. Furthermore, ligation of
      CD40 opposes JNK phosphorylation and activity induced by NGF-beta removal from
      differentiated PC12 cells or serum withdrawal from primary cultured neurons.
      Importantly, CD40 ligation also protects neuronal cells from NGF-beta or serum
      withdrawal-induced injury and affects neuronal differentiation. Finally, adult
      mice deficient for the CD40 receptor demonstrate neuronal dysfunction as
      evidenced by decreased neurofilament isoforms, reduced Bcl-x(L):Bax ratio,
      neuronal morphological change, increased DNA fragmentation, and gross brain
      abnormality. These changes occur with age, and are clearly evident at 16 months.
      Taken together, these data demonstrate a role of CD40 in neuronal development,
      maintenance and protection in vitro and in vivo.

PMID- 11847113
TI  - The centrosomal protein TACC3 is essential for hematopoietic stem cell function
      and genetically interfaces with p53-regulated apoptosis.
AB  - TACC3 is a centrosomal/mitotic spindle-associated protein that is highly
      expressed in a cell cycle-dependent manner in hematopoietic lineage cells. During
      embryonic development, TACC3 is expressed in a variety of tissues in addition to
      the hematopoietic lineages. TACC3 deficiency causes an embryonic lethality at mid
      to late gestation involving several lineages of cells. Hematopoietic stem cells,
      while capable of terminal differentiation, are unable to be expanded in vitro or
      in vivo in reconstitution approaches. Although gross alterations in centrosome
      numbers and chromosomal segregation are not observed, TACC3 deficiency is
      associated with a high rate of apoptosis and expression of the p53 target gene,
      p21(Waf1/Cip1). Hematopoietic stem cell functions, as well as deficiencies in
      other cell lineages, can be rescued by combining the TACC3 deficiency with p53
      deficiency. The results support the concept that TACC3 is a critical component of
      the centrosome/mitotic spindle apparatus and its absence triggers p53-mediated
      apoptosis.

PMID- 11847114
TI  - Oncogenic potential of a C.elegans cdc25 gene is demonstrated by a gain-of
      function allele.
AB  - In multicellular organisms, developmental programmes must integrate with central
      cell cycle regulation to co-ordinate developmental decisions with cell
      proliferation. Hyperplasia caused by deregulated proliferation without
      significant change to other aspects of developmental behaviour is a probable step
      towards full oncogenesis in many malignancies. CDC25 phosphatase promotes
      progression through the eukaryotic cell cycle by dephosphorylation of cyclin
      dependent kinase and, in humans, different cdc25 family members have been
      implicated as potential oncogenes. Demonstrating the direct oncogenic potential
      of a cdc25 gene, we identify a gain-of-function mutant allele of the
      Caenorhabditis elegans gene cdc-25.1 that causes a deregulated proliferation of
      intestinal cells resulting in hyperplasia, while other aspects of intestinal cell
      function are retained. Using RNA-mediated interference, we demonstrate modulation
      of the oncogenic behaviour of this mutant, and show that a reduction of the wild
      type cdc-25.1 activity can cause a failure of proliferation of intestinal and
      other cell types. That gain and loss of CDC-25.1 activity has opposite effects on
      cellular proliferation indicates its critical role in controlling C.elegans cell
      number.

PMID- 11847116
TI  - Unique and overlapping roles for ZipA and FtsA in septal ring assembly in
      Escherichia coli.
AB  - ZipA and FtsA are essential division proteins in Escherichia coli that are
      recruited to the division site by interaction with FtsZ. Utilizing a newly
      isolated temperature-sensitive mutation in zipA we have more fully characterized
      the role of ZipA. We confirmed that ZipA is not required for Z ring formation;
      however, we found that ZipA, like FtsA, is required for recruitment of FtsK and
      therefore all downstream division proteins. In the absence of FtsA or ZipA Z
      rings formed; however, in the absence of both, new Z rings were unable to form
      and preformed Z rings were destabilized. Consistent with this, we found that an
      FtsZ mutant unable to interact with both ZipA and FtsA was unable to assemble
      into Z rings. These results demonstrate that ZipA and FtsA are both required for
      recruitment of additional division proteins to the Z ring, but either one is
      capable of supporting formation and stabilization of Z rings.

PMID- 11847115
TI  - Myb controls G(2)/M progression by inducing cyclin B expression in the Drosophila
      eye imaginal disc.
AB  - The c-myb proto-oncogene product (c-Myb) is a transcriptional activator.
      Vertebrate c-Myb is a key regulator of the G(1)/S transition in cell cycle, while
      Drosophila Myb (dMyb) is important for the G(2)/M transition. Here we report that
      dMyb induces expression of cyclin B, a critical regulator of the G(2)/M
      transition, in Drosophila eye imaginal disc. In the wild-type eye disc, dmyb mRNA
      was expressed in the stripes both anterior and posterior to the morphogenetic
      furrow. Ectopic expression of C-terminal-truncated dMyb in the eye disc caused
      ectopic expression of cyclin B and the rough eye phenotype. This rough eye
      phenotype correlated with prolonged M phase, caused by overexpression of cyclin
      B. Cyclin B expression was lost in dmyb-deficient clones. In Schneider cells, the
      activity of the cyclin B promoter was dramatically reduced by loss of dMyb using
      the RNA interference method. Mutations of the multiple AACNG sequences in the
      cyclin B promoter also abolished the promoter activity. These results indicate
      that dMyb regulates the G(2)/M transition by inducing cyclin B expression via
      binding to its promoter.

PMID- 11847117
TI  - Direct regulation of BCL-2 by FLI-1 is involved in the survival of FLI-1
      transformed erythroblasts.
AB  - Rearrangement of the FLI-1 locus with ensuing overexpression of FLI-1 is an early
      event in Friend murine leukemia virus-induced disease. When overexpressed in
      primary erythroblasts, FLI-1 blocks erythropoeitin (Epo)-induced terminal
      differentiation and inhibits apoptosis normally induced in response to Epo
      withdrawal. We show here that the survival-inducing property of FLI-1 is
      associated with increased transcription of BCL-2. We further show that FLI-1
      binds BCL-2 promoter sequences in transformed erythroblasts, and in vitro studies
      identify specific FLI-1-binding sites essential for the transactivation of the
      BCL-2 promoter by FLI-1. Analysis of FLI-1 mutants showed a correlation between
      the ability of FLI-1 to transactivate BCL-2 promoter sequences and their ability
      to inhibit apoptosis in the absence of Epo. Moreover, inhibitor studies confirmed
      the essential role of BCL-2 for FLI-1-transformed erythroblast survival. Finally,
      enforced expression of BCL-2 was sufficient to promote survival and terminal
      differentiation of erythroblasts in the absence of Epo. These results show that
      BCL-2 is an in vivo target of FLI-1 in FLI-1-transformed erythroblasts and that
      its deregulated expression is instrumental in the survival of these cells.

PMID- 11847118
TI  - Marking the start site of RNA polymerase III transcription: the role of
      constraint, compaction and continuity of the transcribed DNA strand.
AB  - The effects of breaks in the individual strands of an RNA polymerase III promoter
      on initiation of transcription have been examined. Single breaks have been
      introduced at 2 bp intervals in a 24 bp segment that spans the transcriptional
      start site of the U6 snRNA gene promoter. Their effects on transcription are
      asymmetrically distributed: transcribed (template) strand breaks downstream of bp
      14 (relative to the normal start as +1) systematically shift the start site,
      evidently by disrupting the normal mechanism that measures distance from DNA
      bound TBP. Breaks placed close to the normal start site very strongly inhibit
      transcription. Breaks in the non-transcribed strand generate only minor effects
      on transcription. A structure-based model interprets these observations and
      explains how the transcribed strand is used to locate the transcriptional start
      site.

PMID- 11847119
TI  - Transcriptional regulation of fis operon involves a module of multiple coupled
      promoters.
AB  - The transcription of the Escherichia coli fis gene is strongly activated during
      the outgrowth of cells from stationary phase. The high activity of the promoter
      of the fis operon requires the transcription factor IHF. Previously, we
      identified a divergent promoter, div, located upstream of the fis promoter. In
      this study we demonstrate that at least two additional promoters, designated fis
      P2 and fis P3, are located in the control region of the fis operon. The fis P2
      and div promoters overlap completely, whereas fis P3 and div P are arranged as
      face-to-face divergent promoters. We show that the div and the tandem fis
      promoters counterbalance each other, such that their activity is kept on a lower
      than potentially attainable level. Furthermore, we demonstrate an unusual
      activation mechanism by IHF, involving a coordinated shift in the balance of
      promoter activities. We infer that these coupled promoters represent a regulatory
      module and propose a novel "dynamic balance" mechanism involved in the
      transcriptional control of the fis operon.

PMID- 11847120
TI  - Recruitment of the priming protein pTP and DNA binding occur by overlapping Oct-1
      POU homeodomain surfaces.
AB  - The human transcription factor Oct-1 can stimulate transcription from a variety
      of promoters by interacting with the coactivators OBF-1/OCA-B/BOB-1, SNAP190 and
      VP16. These proteins contact Oct-1 regions different from the DNA binding
      surface. Oct-1 also stimulates the DNA replication of adenovirus through its DNA
      binding site in the origin. The Oct-1 POU homeodomain (POUhd) binds the
      adenovirus precursor terminal protein pTP, which serves as the protein primer of
      DNA replication and recruits pTP to the origin. To map the interaction with pTP
      at the POUhd surface, we screened a library of randomly mutated POU domains and
      identified mutations that interfered with pTP interaction and DNA replication
      stimulation. These mutants clustered at a surface different from those recognized
      by OBF-1, SNAP190 and VP16. Unexpectedly, the pTP binding region largely
      overlapped with the DNA binding surface of POUhd. In agreement with this, pTP
      binding and DNA binding were mutually exclusive. We propose a model to reconcile
      pTP recruitment and DNA binding by Oct-1.

PMID- 11847121
TI  - The transcriptional coactivator FHL2 transmits Rho signals from the cell membrane
      into the nucleus.
AB  - GTPases of the Rho family are transducers of extracellular signals and control
      cellular processes such as organization of the actin cytoskeleton, motility,
      adhesion and gene regulation. The Rho signalling pathway is activated, for
      example, by bioactive sphingolipids such as sphingosine-1-phosphate (SPP) or by
      overexpression of Rho family members in tumorigenesis and metastases. Here, we
      show that stimulation of the Rho signalling pathway induces translocation of the
      transcriptional LIM-only coactivator FHL2 to the nucleus and subsequent
      activation of FHL2- and androgen receptor-dependent genes. Interestingly,
      prostate tumours overexpress Rho GTPases and display altered cellular
      localization of FHL2 concomitant with tumour dedifferentiation. SPP-induced FHL2
      activation is mediated by Rho GTPases, but not by the GTPases Cdc42, Rac1 or Ras,
      and depends on Rho-kinase. In addition, Rho signalling influences other
      transcriptional coactivators, thus pointing to a general regulatory role for Rho
      GTPases in cofactor function. In summary, our data propose a yet undescribed
      signalling pathway in which the coactivator FHL2 acts as a novel molecular
      transmitter of the Rho signalling pathway, thereby integrating extracellular cues
      into altered gene expression.

PMID- 11847122
TI  - A chloroplast protein binds a viroid RNA in vivo and facilitates its hammerhead
      mediated self-cleavage.
AB  - Viroids, small single-stranded circular RNAs (246-401 nucleotides), do not have
      mRNA capacity and must recruit host proteins to assist in the steps of their
      biological cycle. The nature of these cellular factors is poorly understood due
      to a lack of reliable experimental approaches. Here, to screen for host proteins
      interacting with viroid RNAs in vivo, we UV-irradiated avocado leaves infected
      with avocado sunblotch viroid (ASBVd), the type member of chloroplast viroids
      containing hammerhead ribozymes. This resulted in the detection of several ASBVd
      host protein adducts. Tandem mass spectrometry analysis of the most abundant
      cross-linked species identified the protein component as two closely related
      chloroplast RNA-binding proteins (PARBP33 and PARBP35) of a family whose members
      previously have been shown to be involved in stabilization, maturation and
      editing of chloroplast transcripts. PARBP33 behaves as an RNA chaperone that
      stimulates in vitro the hammerhead-mediated self-cleavage of the multimeric ASBVd
      transcripts that result from rolling circle replication, indicating that this
      reaction, despite its RNA-based mechanism, is facilitated by proteins. The
      structural and functional parallelism between PARBP33 and PARBP35, and some
      proteins involved in viral RNA replication, indicates that viroids and RNA
      viruses recruit similar host proteins for their replication.

PMID- 11847123
TI  - Binding of tobramycin leads to conformational changes in yeast tRNA(Asp) and
      inhibition of aminoacylation.
AB  - Aminoglycosides inhibit translation in bacteria by binding to the A site in the
      ribosome. Here, it is shown that, in yeast, aminoglycosides can also interfere
      with other processes of translation in vitro. Steady-state aminoacylation
      kinetics of unmodified yeast tRNA(Asp) transcript indicate that the complex
      between tRNA(Asp) and tobramycin is a competitive inhibitor of the aspartylation
      reaction with an inhibition constant (K(I)) of 36 nM. Addition of an excess of
      heterologous tRNAs did not reverse the charging of tRNA(Asp), indicating a
      specific inhibition of the aspartylation reaction. Although magnesium ions
      compete with the inhibitory effect, the formation of the aspartate adenylate in
      the ATP-PP(i) exchange reaction by aspartyl-tRNA synthetase in the absence of the
      tRNA is not inhibited. Ultraviolet absorbance melting experiments indicate that
      tobramycin interacts with and destabilizes the native L-shaped tertiary structure
      of tRNA(Asp). Fluorescence anisotropy using fluorescein-labelled tobramycin
      reveals a stoichiometry of one molecule bound to tRNA(Asp) with a K(D) of 267 nM.
      The results indicate that aminoglycosides are biologically effective when their
      binding induces a shift in a conformational equilibrium of the RNA.

PMID- 11847124
TI  - The hemK gene in Escherichia coli encodes the N(5)-glutamine methyltransferase
      that modifies peptide release factors.
AB  - Class 1 peptide release factors (RFs) in Escherichia coli are N(5)-methylated on
      the glutamine residue of the universally conserved GGQ motif. One other protein
      alone has been shown to contain N(5)-methylglutamine: E.coli ribosomal protein
      L3. We identify the L3 methyltransferase as YfcB and show that it methylates
      ribosomes from a yfcB strain in vitro, but not RF1 or RF2. HemK, a close
      orthologue of YfcB, is shown to methylate RF1 and RF2 in vitro. hemK is
      immediately downstream of and co-expressed with prfA. Its deletion in E.coli K12
      leads to very poor growth on rich media and abolishes methylation of RF1. The
      activity of unmethylated RF2 from K12 strains is extremely low due to the
      cumulative effects of threonine at position 246, in place of alanine or serine
      present in all other bacterial RFs, and the lack of N(5)-methylation of Gln252.
      Fast-growing spontaneous revertants in hemK K12 strains contain the mutations
      Thr246Ala or Thr246Ser in RF2. HemK and YfcB are the first identified
      methyltransferases modifying glutamine, and are widely distributed in nature.

PMID- 11847125
TI  - The retinoblastoma gene product interacts with maintenance human DNA (cytosine-5)
      methyltransferase and modulates its activity.
AB  - The mammalian DNA (cytosine-5) methyltransferase (Dnmt1) is involved in the
      maintenance of methylation patterns in the genome during DNA replication and
      development. The retinoblastoma gene product, Rb, is a cell cycle regulator
      protein that represses transcription by recruiting histone deacetylase (HDAC1).
      In vivo, histone deacetylase associates with Dnmt1. Here we show that Rb itself
      associates with human Dnmt1 (hDnmt1) independently of its own phosphorylation
      status. Methyltransferase activity was co-purified with Rb. The regulatory domain
      of hDnmt1 binds strongly to the B and C pockets of Rb (amino acids 701-872) and
      inhibits methyltransferase activity by disruption of the hDnmt1-DNA binary
      complex. Weak interaction of Rb pockets A and B with Dnmt1 was also observed.
      Overexpression of Rb leads to hypomethylation of the cellular DNA, suggesting
      that Rb may modulate Dnmt1 activity during DNA replication in the cell cycle.

PMID- 11847126
TI  - Structural analysis of an Escherichia coli endonuclease VIII covalent reaction
      intermediate.
AB  - Endonuclease VIII (Nei) of Escherichia coli is a DNA repair enzyme that excises
      oxidized pyrimidines from DNA. Nei shares with formamidopyrimidine-DNA
      glycosylase (Fpg) sequence homology and a similar mechanism of action: the latter
      involves removal of the damaged base followed by two sequential beta-elimination
      steps. However, Nei differs significantly from Fpg in substrate specificity. We
      determined the structure of Nei covalently crosslinked to a 13mer
      oligodeoxynucleotide duplex at 1.25 A resolution. The crosslink is derived from a
      Schiff base intermediate that precedes beta-elimination and is stabilized by
      reduction with NaBH(4). Nei consists of two domains connected by a hinge region,
      creating a DNA binding cleft between domains. DNA in the complex is sharply
      kinked, the deoxyribitol moiety is bound covalently to Pro1 and everted from the
      duplex into the active site. Amino acids involved in substrate binding and
      catalysis are identified. Molecular modeling and analysis of amino acid
      conservation suggest a site for recognition of the damaged base. Based on
      structural features of the complex and site-directed mutagenesis studies, we
      propose a catalytic mechanism for Nei.

PMID- 11847127
TI  - Testing water-mediated DNA recognition by the Hin recombinase.
AB  - The Hin recombinase specifically recognizes its DNA-binding site by means of both
      major and minor groove interactions. A previous X-ray structure, together with
      new structures of the Hin DNA-binding domain bound to a recombination half-site
      that were solved as part of the present study, have revealed that two ordered
      water molecules are present within the major groove interface. In this report, we
      test the importance of these waters directly by X-ray crystal structure analysis
      of complexes with four mutant DNA sequences. These structures, combined with
      their Hin-binding properties, provide strong support for the critical importance
      of one of the intermediate waters. A lesser but demonstrable role is ascribed to
      the second water molecule. The mutant structures also illustrate the prominent
      roles of thymine methyls both in stabilizing intermediate waters and in
      interfering with water or amino acid side chain interactions with DNA.

PMID- 11847128
TI  - A central role for Plasmodium falciparum subtelomeric regions in spatial
      positioning and telomere length regulation.
AB  - In the protozoan malaria parasite, Plasmodium falciparum, the telomere-associated
      sequences (TASs) of the 14 linear chromosomes display a similar higher order
      organization and form clusters of four to seven telomeres localized at the
      nuclear periphery. Experimental evidence has shown that the physical tethering of
      chromosome ends enhances the ectopic recombination between gene families involved
      in antigenic variation and parasite sequestration. Using FISH analysis, we
      observed that chromosome ends lacking the subtelomeric region are usually
      delocalized from telomere clusters, but still remain at the nuclear periphery.
      This indicates that subtelomeric DNA is necessary for cluster formation but is
      not essential for peripheral positioning. Intriguingly, these truncated
      chromosomes have unusually long telomeric tracts (up to three times longer than
      average length), showing that TASs play a role in telomere length regulation. On
      these chromosomes, the newly formed telomere frequently extends from truncated
      genes leading, in some cases, to the transcription of telomeric DNA. The
      implications of both subtelomeric gene expression and nuclear architecture in the
      virulence of this serious human pathogen are discussed.

PMID- 11847130
TI  - ERp44, a novel endoplasmic reticulum folding assistant of the thioredoxin family.
AB  - In human cells, Ero1-Lalpha and -Lbeta (hEROs) regulate oxidative protein folding
      by selectively oxidizing protein disulfide isomerase. Specific protein--protein
      interactions are probably crucial for regulating the formation, isomerization and
      reduction of disulfide bonds in the endoplasmic reticulum (ER). To identify
      molecules involved in ER redox control, we searched for proteins interacting with
      Ero1-Lalpha. Here, we characterize a novel ER resident protein (ERp44), which
      contains a thioredoxin domain with a CRFS motif and is induced during ER stress.
      ERp44 forms mixed disulfides with both hEROs and cargo folding intermediates.
      Whilst the interaction with transport-competent Ig-K chains is transient, ERp44
      binds more stably with J chains, which are retained in the ER and eventually
      degraded by proteasomes. ERp44 does not bind a short-lived ribophorin mutant
      lacking cysteines. Its overexpression alters the equilibrium of the different
      Ero1-Lalpha redox isoforms, suggesting that ERp44 may be involved in the control
      of oxidative protein folding.

PMID- 11847132
TI  - Health literacy: a search for new categories.

PMID- 11847129
TI  - Intracellular trafficking pathway of newly synthesized CD1b molecules.
AB  - The intracellular trafficking of major histocompatibility complex (MHC) class I
      and class II molecules has evolved to support their function in peptide antigen
      presentation optimally. We have analyzed the intracellular trafficking of newly
      synthesized human CD1b, a lipid antigen-presenting molecule, to understand how
      this relates to its antigen-presenting function. Nascent CD1b was transported
      rapidly to the cell surface after leaving the Golgi, and then entered the
      endocytic system by internalization via AP-2-dependent sorting at the plasma
      membrane. A second sorting event, possibly involving AP-3 complexes, led to
      prominent accumulation of CD1b in MHC class II compartments (MIICs). Functional
      studies demonstrated the importance of nascent CD1b for the efficient
      presentation of a foreign lipid antigen. Therefore, the intracellular trafficking
      of nascent CD1b via the cell surface to reach MIICs may allow the efficient
      sampling of lipid antigens present in endocytic compartments.

PMID- 11847131
TI  - SR proteins and hnRNP H regulate the splicing of the HIV-1 tev-specific exon 6D.
AB  - A naturally arising point mutation in the env gene of HIV-1 activates the
      aberrant inclusion of the cryptic exon 6D into most viral messages, leading to
      inefficient viral replication. We set out to understand how a single nucleotide
      substitution could cause such a dramatic change in splicing. We have determined
      that the exon 6D mutation promotes binding of the SR protein SC35 to the exon.
      Mutant exon 6D sequences function as a splicing enhancer when inserted into an
      enhancer-dependent splicing construct. hnRNP H family proteins bind to the
      enhancer as well; their binding is dependent on the sequence GGGA located just
      downstream of the point mutation and depletion-- reconstitution studies show that
      hnRNP H is essential for enhancer activity. A polypurine sequence located further
      downstream in exon 6D binds SR proteins but acts as an exonic splicing silencer.
      hnRNP H is required for interaction of U1 snRNP with the enhancer, independent of
      the point mutation. We propose that SC35 binding to the point mutation region may
      convert the hnRNP H-U1 snRNP complex into a splicing enhancer.

PMID- 11847133
TI  - Breast cancer health promotion model for older Puerto Rican women: results of a
      pilot programme.
AB  - This article focuses on the development of a health promotion model programme for
      elderly Puerto Rican women intended to minimize barriers for early detection of
      breast cancer and to increase women's compliance with recommended guidelines. The
      programme was designed based on the findings of a national sample to assess
      knowledge, beliefs and practices of breast cancer early detection in Puerto Rican
      elderly women and their perceptions of barriers associated with non-compliance.
      It involves the combination of educational and environmental support for actions
      and conditions conducive to health behaviour and consists of the following
      components: (i) a culture- and cohort-sensitive health education programme for
      elderly women on breast cancer screening and assertive strategies for client
      physician relationship; (ii) training for primary-care providers on current
      guidelines and barriers affecting compliance among older women in Puerto Rico;
      and (iii) coordination of necessary support services to facilitate access to
      clinical breast exams and mammograms. Programme implementation considers
      appropriate theories for health promotion and education in the older population.
      Evaluation measured progress in the plan implementation by assessing immediate
      products and long-term impact of the programme. Results of the pilot programme
      revealed a slight increase in knowledge and a significant decrease (p < 0.05) in
      beliefs after the health education sessions. Interventions in breast cancer early
      detection practices showed significant changes (p < 0.05) for mammogram and
      clinical breast examination. Different strategies must be combined to increase
      older women's compliance with breast cancer screening. Health system and access
      barriers to preventive care must be addressed.

PMID- 11847134
TI  - Impact of the Pick the Tick food information programme on the salt content of
      food in New Zealand.
AB  - The Pick the Tick programme of the National Heart Foundation of New Zealand aims
      to provide a framework for cooperation with the food industry to improve
      nutrition labelling and to develop a healthy food supply. Food manufacturers,
      whose products meet defined nutritional criteria, are able to display the Pick
      the Tick logo on food labels. The tick is used by 59% of shoppers in assisting
      them make healthy food choices. Food companies are encouraged to reformulate
      product composition if they fail to meet criteria and develop new products to
      specifically meet the Pick the Tick criteria. The objective of this study was to
      evaluate the impact of the programme on food formulation. The main outcome
      measure was the amount of salt not added to food products. Changes to sodium
      levels were multiplied by the volume of sales and then converted to salt in
      tonnes to provide a tangible measure of the impact of the programme. In a 1-year
      period, July 1998 to June 1999, Pick the Tick influenced food companies to
      exclude approximately 33 tonnes of salt through the reformulation and formulation
      of 23 breads, breakfast cereals and margarine. Breakfast cereals showed the
      largest reduction in sodium content by an average of 378 mg sodium per 100 g
      product (61%). Bread was reduced by an average of 123 mg per 100 g product (26%)
      and margarine by 53 mg per 100 g (11%). Pick the Tick appeals to the food
      industry as a tool for marketing food products and has provided an incentive to
      improve the nutritional value of foods. The tick on approved products not only
      acts as a 'nutrition signpost' for consumers but can also significantly influence
      the formulation of products without sacrificing taste or quality.

PMID- 11847135
TI  - School journeys and leisure activities in rural and urban adolescents in Norway.
AB  - Health promotion measures in order to increase physical activity should include
      environmental and policy approaches. Studies in natural living environments such
      as rural and urban areas may provide valuable information about the effects of
      environmental factors on physical activity. The present study was performed among
      88 adolescents living in one rural and one urban area in Norway, with particular
      focus on the availability of cycling tracks and walking trails. The study showed
      that both rural and urban adolescents spent more time on sedentary activities,
      such as watching TV/video and playing TV/data-games, than on regular physical
      activity. No differences were observed between the two groups in regard to
      activity patterns. However, the median distance the urban adolescents walked or
      cycled to school was three times greater than the median distance the rural
      adolescents walked or cycled to a bus stop or to school. The urban adolescents
      also walked or cycled more to regular activities than the rural ones. Positive
      correlations were found between walking or cycling from home to school and
      walking or cycling to regular activities. In multiple regression analysis, urban
      area, female gender and distance walked or cycled to school or bus stop predicted
      increased walking or cycling to activities. The results confirm other studies on
      adolescents, showing that much more time is spent on sedentary rather than on
      physical activity. Knowledge is still lacking concerning predictors of sedentary
      and general physical activity, but the results indicate that access to cycling
      tracks and walking trails in residential areas may increase both walking or
      cycling to school and to leisure activities. A relevant strategy for health
      promotion may therefore be to make cycling tracks and walking trails accessible;
      some passive transport both to school and to leisure activities may thus probably
      be replaced by walking or cycling.

PMID- 11847136
TI  - More than words? The status and impact of smoking policies in Scottish schools.
AB  - The aim of this study was to investigate the current status of smoking policies
      in Scottish schools, and the relationship between policy status, enforcement of
      smoking restrictions and perceptions of smoking behaviour among pupils and
      teachers. A representative sample of 15-year-old school pupils from 77 Scottish
      secondary schools was surveyed in 1998 regarding their perceptions of smoking in
      several locations within and outside the school building. Two staff members from
      each school were also surveyed regarding school smoking policies for pupils and
      teachers, the nature of the school's smoking restrictions, and the extent to
      which the restrictions were enforced. The results showed that more schools had a
      written policy on teacher smoking than on pupil smoking. All schools in the
      sample banned smoking by pupils, but the majority allowed smoking by teachers in
      restricted areas. Irrespective of the type of policy or restrictions on smoking,
      pupils reported seeing smoking among both pupils and teachers on school premises
      in all of the sample schools. Whether or not a school had a written policy
      appeared to be unrelated to pupil smoking in the toilets or teacher smoking
      outdoors on school premises. However, pupils were less likely to be aware of
      pupils smoking outdoors and teachers smoking in the staff rooms in schools where
      there were written policies on pupil and teacher smoking, respectively.
      Consistent enforcement of a ban on pupil smoking was associated with lower levels
      of perceived smoking among pupils. Where a complete ban on teacher smoking
      existed, smoking among teachers was seen less often in the staff rooms, but more
      often in outside areas on school premises. The results have implications for the
      use of policy in promoting a healthy school environment.

PMID- 11847137
TI  - Cost-effectiveness of a community anti-smoking campaign targeted at a high risk
      group in London.
AB  - Surveys of Turkish speaking people in London found 74% of men and 45% of women
      were smokers, and knowledge of the health effects of smoking was low. Camden and
      Islington Health Authority has a substantial Turkish community. We report an
      economic evaluation of a community smoking cessation intervention, aimed at the
      Turkish community, undertaken by Camden and Islington Health Promotion Agency.
      The intervention aimed to highlight the dangers of smoking, and to reduce the
      amount smoked and the number of current smokers. It included a play, a poster and
      media campaign, and purpose-designed leaflets. A panel survey of the Turkish
      population determined smoking habits, attitudes to smoking and knowledge about
      the health effects at baseline and 12 months. The intervention effect was
      estimated from the changes between baseline and final surveys. To allow for the
      non-response to the second survey we analysed effectiveness in two ways: first by
      assuming that the responders represented the true situation, and secondly by
      making a more pessimistic assumption that there was no change in the non
      responders. Fifty-seven per cent of the Turkish population were smokers at
      baseline, compared with 39% in the general population of Camden and Islington.
      Levels were particularly high in younger women. At follow-up there was a net
      reduction in smokers of 6.4% [95% confidence interval (CI) 0-13.6%] in
      responders. When all study subjects were included the net reduction was 2.9% (CI
      0-6.3%). Most quitters were light smokers to start with. At follow-up, 51% of
      respondents recognized at least one of the Turkish language interventions. The
      estimated cost-effectiveness of this intervention was 105 pound (range 33-391
      pound) per life year gained. Campaigns targeted at groups with high smoking
      prevalence may be more cost-effective than general population campaigns.

PMID- 11847138
TI  - Impacts from repeated mass media campaigns to promote sun protection in
      Australia.
AB  - Campaigns using television, radio and print media were conducted over three
      summers in New South Wales, Australia, aiming to increase the use of sun
      protection measures among children under 12 years. The evaluation entailed cross
      sectional telephone surveys before and after each of the first two campaigns and
      following the third campaign. The study group were parents of children under 12
      years. Random digit dialling yielded samples of approximately 800 for each
      survey. Measures addressed campaign recall and sun protection knowledge,
      attitudes and behaviours. The surveys revealed significant levels of campaign
      recall. Knowledge about the protective benefits of sunscreens, hats and
      protective clothing was high at baseline and showed little improvement over the
      campaigns. Knowledge levels about the benefits of shade cover and of the relative
      risks of skin cancer from childhood sun exposure were lower, and also did not
      show improvement. Just one of the four attitude factors showed significant
      improvement, and this concerned the importance that parents placed on the issue
      of child sun protection. After the final campaign there were increases compared
      with baseline in childrens' use of sunscreen, protective clothing and shade, but
      it was notable that between campaigns levels of these behaviours were similar to
      or below those at baseline. There was no evidence of a campaign-related increase
      in hat wearing by children. All sun protection measures were used less often by
      adults than children, but these showed similar trends. Mass media campaigns may
      contribute to short-term increases in some sun protection behaviours; however, as
      their impact is not sustained they should be repeated and supplemented by
      educational, policy and environmental strategies.

PMID- 11847139
TI  - Influence of health promotion bureaucracy on community participation: a Canadian
      case study.
AB  - The purpose of this paper is to illustrate, through a Canadian case study, the
      bureaucratic support and obstacles for community participation in health
      promotion. The paper begins with a brief history of the development of a
      participatory health promotion programme in Canada. The role of bureaucracies on
      participation of communities is highlighted. Secondly, the paper describes how a
      variety of bureaucratic factors affected grassroots community participation
      efforts of local projects in one province. Finally, discussion focuses on how
      community participation is constrained in a bureau-cratically mediated activity
      such as health promotion.

PMID- 11847140
TI  - Closing the gap: building the capacity of non-government organizations as
      advocates for health equity.
AB  - Seeking achievement of health equity has underpinned national government and
      global health policies for decades. However, major difficulties and challenges
      faced in the practice of achieving 'Health for All' has led to a recognition of
      the need to broaden the focus of efforts to improve health equity. Civil society
      groups have been identified as key stakeholders in attempts to achieve health
      equity, and the importance of strengthening their capacity to influence relevant
      government policy and practice has been highlighted. This paper presents the
      results of a qualitative study which examined the role of organizations outside
      government in advocating for health equity, and the capacities and conditions
      that were related to their success. In-depth, unstructured interviews were
      conducted with 26 non-government organizations (NGOs) who were active in three
      important health policy debates in Australia. The grounded theory method was used
      to direct data collection and analysis, and member checking was employed to
      ensure soundness and build ownership of the findings. Effective advocacy was
      found to be a dynamic process characterized by flexibility and opportunism within
      a framework of longer term goals. Two key ways of working were identified--in
      partnership and in conflict with government, with shifts in emphasis in response
      to organizational strengths and a changing environment. A number of domains of
      capacity, which together are termed 'capacity for advocacy', were also
      identified. It is clear that NGOs can learn a great deal from each other, but
      there needs to be investment by governments, international agencies and NGOs
      themselves if advocacy for health equity is to be strengthened.

PMID- 11847141
TI  - Well-being in schools: a conceptual model.
AB  - Health and well-being have mostly been separated from other aspects of school
      life. Health services and health education have been available for school-aged
      children in Western societies for a long time. Recently, more comprehensive
      school health programmes have been developed, e.g. the WHO 'health promoting
      school' and 'coordinated school health programme' in the USA. They focus on how
      to implement health promotion and health education in school. However, a
      theoretically grounded model based on the sociological concept of well-being is
      needed for planning and evaluation of school development programmes. The School
      Well-being Model is based on Allardt's sociological theory of welfare and
      assesses well-being as an entity in school setting. Well-being is connected with
      teaching and education, and with learning and achievements. Indicators of well
      being are divided into four categories: school conditions (having), social
      relationships (loving), means for self-fulfilment (being) and health status.
      'Means for self-fulfilment' encompasses possibilities for each pupil to study
      according to his/her own resources and capabilities. 'Health status' is seen
      through pupils' symptoms, diseases and illnesses. Each well-being category
      contains several aspects of pupils' life in school. The model takes into account
      the important impact of pupils' homes and the surrounding community. Compared
      with others, The School Well-being Model's main differences are the use of the
      well-being concept, the definition of health and the subcategory means for self
      fulfilment. Making the outline of the well-being concept facilitates the
      development of theoretically grounded subjective and objective well-being
      indicators.

PMID- 11847142
TI  - Role of knowledge in public health and health promotion policy change.
AB  - A framework of policy development is presented that identifies the role various
      forms of knowledge can play in the policy formation process. The framework is
      based upon the premise that public health and health promotion issues should be
      addressed within an analysis of policy change that considers concepts of
      interactive and critical knowledge in addition to scientific knowledge. Progress
      in developing meaningful health policy will require accepting the validity of
      these various forms of knowledge and developing frameworks that see experts and
      citizens working together to develop and achieve public health and health
      promotion goals.

PMID- 11847143
TI  - Death following coronary angioplasty.

PMID- 11847145
TI  - Intracoronary stenting: developments since the NICE report.

PMID- 11847146
TI  - Mechanical reperfusion therapy for acute myocardial infarction: Stent PAMI,
      ADMIRAL, CADILLAC and beyond.

PMID- 11847147
TI  - More light on QT interval measurement.

PMID- 11847148
TI  - New coronary imaging techniques: what to expect?

PMID- 11847149
TI  - Training in academic cardiology: prospects for a better future.

PMID- 11847151
TI  - Inflammation in acute coronary syndromes.
AB  - Extensive evidence supports a pathogenic role for both local and systemic
      inflammation in acute coronary syndromes. However, several important questions
      remain unanswered. Is the observed inflammatory process a precursor or a
      consequence of coronary plaque rupture? Is the inflammatory component of unstable
      coronary disease a potential therapeutic target? Finally, do infectious agents
      have a pathogenic role in coronary atherosclerosis and acute coronary syndromes?

PMID- 11847152
TI  - Virtual coronary angioscopy using multislice computed tomography.
AB  - BACKGROUND: With faster image acquisition times and thinner slice widths,
      multislice detector computed tomography (MSCT) allows visualisation of human
      coronary arteries with diagnostic image quality. In addition to conventional
      axial slices, virtual coronary angioscopies (VCA) can be reconstructed using MSCT
      datasets. OBJECTIVE: To evaluate the feasibility of reconstructing VCA and to
      determine the clinical value of this new application in detecting atherosclerotic
      coronary artery lesions. METHODS: Datasets obtained by contrast enhanced non
      invasive coronary angiography using MSCT (Somatom VZ) were analysed from 14
      consecutive patients. VCA were simulated in 14 coronary arteries (left anterior
      descending, n = 7; right coronary, n = 7). Lesion detection was undertaken on
      conventional contrast enhanced axial slices, as well as by VCA. Intracoronary
      ultrasound (ICUS) was used as the gold standard for in vivo plaque detection.
      RESULTS: 38 lesions were detected both on ICUS and on axial slices: 14 severe
      target lesions of > 75% area stenosis (11 calcified, three non-calcified), and 24
      intermediate lesions of < or = 75% area stenosis (seven calcified, 17 non
      calcified). Using VCA, all severe lesions (n = 14) and all calcified intermediate
      plaques (n = 7) could clearly be identified. However, non-calcified intermediate
      lesions (n = 17) could not be accurately distinguished from the vessel wall; they
      were recognised as vessel wall alterations without significant luminal narrowing.
      CONCLUSIONS: Current MSCT technology allows reconstruction of VCA with good image
      quality. Despite a more anatomical view of heart and coronary vessels on three
      dimensional reconstruction, conventional axial slices were found to be superior
      for detecting coronary lesions. Thus further technical innovations are required
      before VCA can become a useful technique in clinical cardiology.

PMID- 11847153
TI  - Images in cardiology. Incorrect administration of buccal glyceryl trinitrate.

PMID- 11847155
TI  - Images in cardiology. Atrioventricular septal defect with cor triatriatum.

PMID- 11847154
TI  - Active versus borderline myocarditis: clinicopathological correlates and
      prognostic implications.
AB  - OBJECTIVE: To compare active (AM) with borderline (BM) myocarditis to verify
      whether the pathological distinction between the two forms may help to identify
      patients with different clinical and haemodynamic characteristics and to aid
      prognosis. MATERIALS: Myocarditis was diagnosed in 56 patients on endomyocardial
      biopsy (EMB) within one year from clinical onset of the disease between 1991 and
      1998. Fourteen patients were excluded because of a lack of adequate and complete
      information. EMBs and clinical records of the 42 remaining patients were
      reviewed. Immunohistochemistry on bioptic samples was regularly performed.
      Polymerase chain reaction (PCR) for a panel of viruses was performed in 23
      patients (55%). Clinicopathological correlations were calculated. RESULTS: The
      histological diagnosis was AM in 26 patients (62%) and BM in 16 (38%).
      Significant differences were found in the following parameters: presence of left
      bundle branch block on ECG (AM 2 (8%) v BM 5 (31%), p = 0.05); left ventricular
      volume on echocardiogram (mean (SD) AM 90 (42) ml/m(2) v BM 128 (50) ml/m(2), p =
      0.002); mass to volume ratio (AM 1.0 (0) v BM 0.8 (0.1), p = 0.03); time interval
      between clinical onset of the disease and EMB (AM 40 (55) v BM 90 (93) days, p =
      0.04); and degree of inflammatory infiltrates, scored on a scale of 0 to 3 (AM
      1.65 (0.8) v BM 0.85 (0.3), p = 0.004). In 6 of 15 patients (40%) with AM and in
      2 of 8 (25%) with BM, a viral genome was detected by PCR (NS). At follow up, no
      differences in death or heart transplantation were detected between the two forms
      (AM 4 patients (15%) v BM 2 patients (12.5%)). Three of eight PCR positive
      patients (37.5%) and 1 of 15 virus negative patients (7%) died or underwent heart
      transplantation. CONCLUSIONS: BM seems to encompass inflammatory forms with a
      less aggressive inflammatory infiltrate evolving towards left ventricular
      dilatation. The term "chronic myocarditis" seems to be more appropriate. The
      absence of myocyte necrosis does not predict a more favourable prognosis, whereas
      the absence of a viral genome seems to predict it.

PMID- 11847156
TI  - Restricted weekend service inappropriately delays discharge after acute
      myocardial infarction.
AB  - BACKGROUND: Early discharge after myocardial infarction is safe and feasible.
      Factors that delay discharge need to be identified in order to improve care and
      reduce bed occupancy. OBJECTIVE: To investigate the potential of the restricted
      weekend service that operates in most hospitals to delay patient discharge.
      DESIGN: Prospective cohort study. SUBJECTS AND SETTING: 2541 consecutive patients
      with acute myocardial infarction admitted to the coronary care unit of three
      local district hospitals over a 12 year period. RESULTS: Clinical factors
      affecting the duration of stay were age, sex, and severity of infarction. Thus
      older patients and women stayed significantly longer, as did patients with
      enzymatically large infarcts. Day of week also had an important influence on
      duration of stay. Discharge occurred most often on a Friday (p = 0.006) and least
      often over the weekend (p = 0.0001). Patients were preferentially discharged on a
      Friday if the length of stay was more than 72 hours. Thus patients admitted on a
      Sunday or Monday were usually discharged the following Friday, corresponding to a
      median duration of stay of five or four days, respectively. For patients admitted
      on Tuesday to Saturday, weekend discharge was avoided and the median duration of
      stay was six to eight days. CONCLUSIONS: For patients with acute myocardial
      infarction, discharge decisions were influenced appropriately by clinical
      indicators of risk, but inappropriately by the day of the week. Thus weekend
      discharge was generally avoided, leading to variations in length of stay that
      were largely determined by the day of the week on which admission occurred rather
      than clinical need.

PMID- 11847157
TI  - Images in cardiology. A case of spontaneous closure of coronary artery fistula
      with familial hypercholesterolaemia.

PMID- 11847158
TI  - Relation between QT and RR intervals is highly individual among healthy subjects:
      implications for heart rate correction of the QT interval.
AB  - OBJECTIVE: To compare the QT/RR relation in healthy subjects in order to
      investigate the differences in optimum heart rate correction of the QT interval.
      METHODS: 50 healthy volunteers (25 women, mean age 33.6 (9.5) years, range 19-59
      years) took part. Each subject underwent serial 12 lead electrocardiographic
      monitoring over 24 hours with a 10 second ECG obtained every two minutes. QT
      intervals and heart rates were measured automatically. In each subject, the QT/RR
      relation was modelled using six generic regressions, including a linear model (QT
      = beta + alpha x RR), a hyperbolic model (QT = beta + alpha/RR), and a parabolic
      model (QT = beta x RR(alpha)). For each model, the parallelism and identity of
      the regression lines in separate subjects were statistically tested. RESULTS: The
      patterns of the QT/RR relation were very different among subjects. Regardless of
      the generic form of the regression model, highly significant differences were
      found not only between the regression lines but also between their slopes. For
      instance, with the linear model, the individual slope (parameter alpha) of any
      subject differed highly significantly (p < 0.000001) from the linear slope of no
      fewer than 21 (median 32) other subjects. The linear regression line of 20
      subjects differed significantly (p < 0.000001) from the linear regression lines
      of each other subject. Conversion of the QT/RR regressions to QTc heart rate
      correction also showed substantial intersubject differences. Optimisation of the
      formula QTc = QT/RR(alpha) led to individual values of alpha ranging from 0.234
      to 0.486. CONCLUSION: The QT/RR relation exhibits a very substantial intersubject
      variability in healthy volunteers. The hypothesis underlying each prospective
      heart rate correction formula that a "physiological" QT/RR relation exists that
      can be mathematically described and applied to all people is incorrect. Any
      general heart rate correction formula can be used only for very approximate
      clinical assessment of the QTc interval over a narrow window of resting heart
      rates. For detailed precise studies of the QTc interval (for example, drug
      induced QT interval prolongation), the individual QT/RR relation has to be taken
      into account.

PMID- 11847159
TI  - Effect of allopurinol on mortality and hospitalisations in chronic heart failure:
      a retrospective cohort study.
AB  - OBJECTIVE: To examine whether allopurinol is associated with any alteration in
      mortality and hospitalisations in patients with chronic heart failure (CHF). This
      hypothesis is based on previous data that a high urate concentration is
      independently associated with mortality with a risk ratio of 4.23 in CHF. DESIGN:
      Retrospective cohort study. SETTING: Medicines Monitoring Unit, Ninewells
      Hospital, Dundee, UK. PATIENTS: 1760 CHF patients divided into four groups: those
      on no allopurinol, those on long term low dose allopurinol, those on short term
      low dose allopurinol, and those on long term high dose allopurinol. MAIN OUTCOME
      MEASURES: Total mortality, cardiovascular mortality, cardiovascular
      hospitalisations, cardiovascular mortality or hospitalisations. RESULTS: Long
      term low dose allopurinol was associated with a significant worsening in
      mortality over those who never received allopurinol (relative risk 2.04, 95%
      confidence interval (CI) 1.48 to 2.81). This may be because low dose allopurinol
      is insufficient to negate the adverse effect of a high urate concentration.
      However, long term high dose (> or = 300 mg/day) allopurinol was associated with
      a significantly better mortality than longstanding low dose allopurinol (relative
      risk 0.59, 95% CI 0.37 to 0.95). This may mean that high dose allopurinol can
      fully negate the adverse effect of urate and return the mortality to normal.
      CONCLUSIONS: Long term high dose allopurinol may be associated with a better
      mortality than long term low dose allopurinol in patients with CHF because of a
      dose related beneficial effect of allopurinol against the well described adverse
      effect of urate. Further work is required to substantiate or refute this finding.

PMID- 11847160
TI  - Images in cardiology. Haemopericardium and Brugada-like ECG pattern in rheumatoid
      arthritis.

PMID- 11847161
TI  - Health related quality of life in patients with congestive heart failure:
      comparison with other chronic diseases and relation to functional variables.
AB  - OBJECTIVE: To assess health related quality of life of patients with congestive
      heart failure; to compare their quality of life with the previously characterised
      general population and in those with other chronic diseases; and to correlate the
      different aspects of quality of life with relevant somatic variables. SETTING:
      University hospital. PATIENTS AND DESIGN: A German version of the generic quality
      of life measure (SF-36) containing eight dimensions was administered to 205
      patients with congestive heart failure and systolic dysfunction. Cardiopulmonary
      evaluation included assessment of New York Heart Association (NYHA) functional
      class, left ventricular ejection fraction, peak oxygen uptake, and the distance
      covered during a standardised six minute walk test. RESULTS: Quality of life
      significantly decreased with NYHA functional class (linear trend: p < 0.0001). In
      NYHA class III, the scores of five of the eight quality of life domains were
      reduced to around one third of those in the general population. The pattern of
      reduction was different in patients with chronic hepatitis C and major
      depression, and similar in patients on chronic haemodialysis. Multiple regression
      analysis showed that only the NYHA functional class was consistently and closely
      associated with all quality of life scales. The six minute walk test and peak
      oxygen uptake added to the explanation of the variance in only one of the eight
      quality of life domains (physical functioning). Left ventricular ejection
      fraction, duration of disease, and age showed no clear association with quality
      of life. CONCLUSIONS: In congestive heart failure, quality of life decreases as
      NYHA functional class worsens. Though NYHA functional class was the most dominant
      predictor among the somatic variables studied, the major determinants of reduced
      quality of life remain unknown.

PMID- 11847162
TI  - Images in cardiology. Successful coronary artery stenting for spontaneous
      coronary artery dissection.

PMID- 11847163
TI  - Increased pericardial fluid concentrations of the mature form of adrenomedullin
      in patients with cardiac remodelling.
AB  - BACKGROUND: There is evidence that adrenomedullin has autocrine or paracrine
      activities that oppose cardiac remodelling. However, it remains unclear whether
      it exerts those local functions in heart failure patients. OBJECTIVE: To
      investigate the relation between plasma and pericardial fluid concentrations of
      adrenomedullin and left ventricular haemodynamic variables. DESIGN: Samples of
      plasma and pericardial fluid were obtained from 50 patients undergoing cardiac
      surgery. They were classified into two groups: group N (n = 27) with a left
      ventricular end diastolic volume index (LVEDVI) < or = 90 ml/m(2); and group R (n
      = 23) with LVEDVI > 90 ml/m(2). Plasma and pericardial fluid concentrations of
      total adrenomedullin (tAM) and mature adrenomedullin (mAM) were measured and
      related to the preoperative haemodynamic variables. RESULTS: Pericardial fluid
      concentrations of mAM were much higher than the plasma concentration in both
      group N and group R (mean (SEM), 10.6 (1.7) v 3.3 (0.2) fmol/ml, p = 0.0001; and
      21.2 (2.8) v 3.9 (0.3) fmol/ml, p < 0.0001, respectively). The ratio mAM/tAM in
      pericardial fluid was significantly higher than in plasma (0.56 (0.02) v 0.28
      (0.02), p < 0.0001). Pericardial fluid concentrations of mAM, but not plasma
      concentrations, were significantly correlated with LVEDVI, left ventricular end
      systolic volume index, left ventricular ejection fraction, and left ventricular
      mass index (r = 0.60, 0.63, -0.54, and 0.47, respectively). CONCLUSIONS: Raised
      pericardial fluid concentrations of mAM may reflect the actions of adrenomedullin
      as a local mediator against cardiac remodelling in patients with left ventricular
      dysfunction.

PMID- 11847164
TI  - Left ventricular diastolic function assessed using Doppler tissue imaging in
      patients with hypertrophic cardiomyopathy: relation to symptoms and exercise
      capacity.
AB  - BACKGROUND: Conventional Doppler indices of left ventricular diastolic function
      do not correlate with symptoms or exercise capacity in patients with hypertrophic
      cardiomyopathy, because of their dependence on loading conditions. Diastolic
      mitral annular velocity measured using Doppler tissue imaging has been reported
      to be a preload independent index of left ventricular diastolic function.
      OBJECTIVE: To determine the relation between diastolic annular velocities
      combined with conventional Doppler indices and symptoms or exercise capacity in
      hypertrophic cardiomyopathy. METHODS: 85 patients with hypertrophic
      cardiomyopathy and 60 normal controls were studied. Diastolic mitral annular
      velocities, transmitral left ventricular filling, and pulmonary venous velocities
      were measured. RESULTS: Early diastolic velocities at lateral and septal annulus
      were lower in patients with hypertrophic cardiomyopathy than in controls (lateral
      Ea: 10 (3) v 18 (4) cm/s, p < 0.0001; septal Ea: 7 (2) v 12 (3) cm/s, p <
      0.0001). Unlike conventional Doppler indices alone, transmitral early left
      ventricular filling velocity (E) to lateral Ea ratio correlated inversely with
      peak oxygen consumption (r = -0.42, p < 0.0001). Patients in New York Heart
      Association (NYHA) class III had a higher transmitral E to lateral Ea ratio (12.0
      (4.6)) than those in NYHA class II (7.6 (3.1), p < 0.005) or class I (6.6 (2.6),
      p < 0.0001). CONCLUSIONS: Early diastolic mitral annular velocities are reduced
      in patients with hypertrophic cardiomyopathy. Unlike conventional Doppler indices
      alone, the transmitral E to lateral Ea ratio correlates with NYHA functional
      class and exercise capacity.

PMID- 11847165
TI  - Impact of angiotensin converting enzyme inhibition on post-coronary artery bypass
      interleukin 6 release.
AB  - BACKGROUND: Angiotensin 1 converting enzyme (ACE) inhibitors reduce morbidity and
      mortality after coronary artery bypass graft surgery (CABG). This benefit may
      result from an anti-inflammatory action. OBJECTIVE: To examine the effect of ACE
      inhibition on interleukin 6 (IL-6) concentrations after CABG. PATIENTS AND
      METHODS: 161 patients undergoing elective first time CABG were recruited, of whom
      41 (25%) were receiving ACE inhibitor treatment; 21 patients with confounding
      postoperative complications were excluded. After these exclusions there were 33
      patients (24%) on ACE inhibitor treatment. Plasma IL-6 was measured
      preoperatively and again six hours after CABG. RESULTS: Baseline IL-6
      concentrations (geometric mean (SEM)) were non-significantly lower among the
      patients receiving ACE inhibitors (3.7 (0.1) v 4.3 (0.1) pg/ml, p = 0.12).
      Overall, post-CABG IL-6 concentrations increased significantly (mean rise 177
      (12) pg/ml, p < 0.0005). This response was blunted among ACE inhibitor treated
      patients. Median increases in IL-6 concentrations were 117 v 193 pg/ml, for
      treated v non-treated patients, respectively (Kruskal-Wallis, p = 0.02), with
      peak postoperative IL-6 concentrations lower among the subjects receiving ACE
      inhibitors than in untreated subjects (142 (19) v 196 (13) pg/ml, p = 0.02). The
      effect of ACE inhibitors remained significant after multivariate analysis (p =
      0.018). CONCLUSIONS: ACE inhibitor treatment is associated with a reduction in IL
      6 response to CABG. The data suggest that this class of drug may have a direct
      anti-inflammatory effect, which could explain some of its clinical benefit.

PMID- 11847166
TI  - Natural history of growth of secundum atrial septal defects and implications for
      transcatheter closure.
AB  - OBJECTIVE: To investigate the natural history of secundum atrial septal defects
      (ASDs) over several years using serial echocardiographic studies. METHODS: All
      patients with isolated secundum ASDs who had serial transthoracic echocardiograms
      at Texas Children's Hospital, Houston, Texas, from January 1991 to December 1998
      were identified. Patients with fenestrated or multiple ASDs, other congenital
      heart defects, or less than a six month interval between echocardiograms were
      excluded. There were 104 patients eligible for inclusion in the study. Studies
      were reviewed by two echocardiographers (blinded) and the maximal diameter was
      recorded. Defects were defined as small (> 3 mm to < 6 mm), moderate (> or = 6 mm
      to < 12 mm), or large (> or = 12 mm). ASDs that grew > or = 20 mm were defined as
      having outgrown transcatheter closure with the device available to the authors'
      institution. RESULTS: ASD diameter increased in 68 of 104 patients (65%),
      including 31 patients (30%) with a > 50% increase in diameter. Spontaneous
      closure occurred in four patients (4%). Thirteen defects (12%) increased to > or
      = 20 mm. One fifth of the patients studied had an insufficient atrial rim by
      transthoracic echocardiogram to hold an atrial septal occluder. The only factor
      associated with significant growth of ASDs was initial size of the defect. ASD
      growth was independent both of age at diagnosis and when indexed to body surface
      area. CONCLUSIONS: Two thirds of secundum ASDs may enlarge with time and there is
      the potential for secundum ASDs to outgrow transcatheter closure with specific
      devices. Further development in devices and general availability of devices
      capable of closing larger ASDs should circumvent this problem.

PMID- 11847167
TI  - Transcatheter closure of high pulmonary artery pressure persistent ductus
      arteriosus with the Amplatzer muscular ventricular septal defect occluder.
AB  - BACKGROUND: The design of devices currently used for closure of persistent ductus
      arteriosus (PDA) with high pulmonary artery pressure is not ideal and there is a
      risk of embolisation into the aorta. OBJECTIVE: To investigate the use of the
      Amplatzer muscular ventricular septal defect occluder (AMVSDO) for treatment of
      PDA with high pulmonary artery pressure. PATIENTS AND DESIGN: Seven patients,
      aged 5-12 years, with large PDAs and systemic or near systemic pulmonary artery
      pressure underwent attempted transcatheter closure using the AMVSDO. The device
      consists of two low profile disks made of a nitinol wire mesh with a 7 mm
      connecting waist. Balloon occlusion of the duct was performed before closure from
      the venous side, and prosthesis size was chosen according to the measured
      diameter of the occluding balloon. A 7 French sheath was used to deliver the
      device. All patients underwent a complete haemodynamic and angiographic study one
      year after occlusion. RESULTS: The mean (SD) angiographic PDA diameter was 9.8
      (1.7) mm (range 7-13 mm) and the mean AMVSDO diameter was 11.4 (1.8) mm (range 9
      16 mm). Q(p)/Q(s) ranged from 1.9-2.2 (mean 2.0 (0.1)). Successful device
      delivery and complete closure occurred in all patients (100% occlusion rate, 95%
      confidence interval 59.04% to 100.00%). Mean systolic pulmonary artery pressures
      were as follows: before balloon occlusion, 106 (13) mm Hg; during occlusion, 61
      (6) mm Hg; immediately after the procedure, 57 (5) mm Hg; and at the one year
      follow up catheterisation, 37 (10) mm Hg. Fluoroscopy time was 10.4 (4.3) min
      (range 7-18 min). No complications occurred. CONCLUSIONS: AMVSDO is an important
      adjunct for closure of large PDAs associated with high pulmonary artery pressure.
      Further studies are required to document its efficacy, safety, and long term
      results in a larger number of patients.

PMID- 11847168
TI  - Images in cardiology. Aortic abscess to right atrium fistula.

PMID- 11847171
TI  - Images in cardiology. Paraoesophageal hiatal hernia as a rare cause of dyspnoea.

PMID- 11847169
TI  - Tetrahydrobiopterin restores endothelial function of coronary arteries in
      patients with hypercholesterolaemia.
AB  - OBJECTIVE: To examine the effect of tetrahydrobiopterin (BH4), an essential
      cofactor for nitric oxide synthase, on coronary artery endothelial function in
      hypercholesterolaemic patients. DESIGN: Quantitative coronary angiography and
      Doppler flowmetry were used to examine the effects of intracoronary infusion of
      BH4 on vascular response to acetylcholine (ACh). SETTING: Tertiary cardiology
      centre. PATIENTS: 18 patients with angiographically normal coronary arteries, of
      whom nine had hypercholesterolaemia and nine had noromocholesterolaemia.
      INTERVENTIONS: ACh (3 and 30 microg/min) was infused for two minutes into the
      left coronary ostium. ACh was then simultaneously infused with BH4 (1 mg/min)
      before and after infusion of L-N(G)-monomethyl-L-arginine (L-NMMA) (40
      micromol/min for five minutes). MAIN OUTCOME MEASURES: Diameter of the epicardial
      coronary arteries and coronary blood flow. RESULTS: In hypercholesterolaemic
      patients, BH4 attenuated the ACh induced decrease in coronary diameter (p < 0.05)
      and restored the ACh induced increase in coronary blood flow (p < 0.05). In
      normocholesterolaemic patients, BH4 did not affect the ACh induced changes in
      coronary diameter or coronary blood flow. In both groups, L-NMMA decreased the
      baseline coronary diameter (p < 0.05) and baseline coronary blood flow (p <
      0.05). In hypercholesterolaemic patients, L-NMMA inhibited both the BH4 mediated
      attenuation of the ACh induced decrease in coronary diameter (p < 0.05) and the
      BH4 mediated enhancement of the ACh induced increase in coronary blood flow (p <
      0.01). CONCLUSIONS: Intracoronary infusion of BH4 restores coronary endothelial
      function by improving the bioavailability of endothelium derived nitric oxide in
      hypercholesterolaemic patients.

PMID- 11847170
TI  - Genetic polymorphisms in the renin-angiotensin-aldosterone system associated with
      expression of left ventricular hypertrophy in hypertrophic cardiomyopathy: a
      study of five polymorphic genes in a family with a disease causing mutation in
      the myosin binding protein C gene.
AB  - BACKGROUND: Hypertrophic cardiomyopathy (HCM) is an inherited disease of the
      sarcomere characterised clinically by myocardial hypertrophy and its
      consequences. Phenotypic expression is heterogeneous even within families with
      the same aetiological mutation and may be influenced by additional genetic
      factors. OBJECTIVE: To determine the influence of genetic polymorphisms of the
      renin-angiotensin-aldosterone system (RAAS) on ECG and two dimensional
      echocardiographic left ventricular hypertrophy (LVH) in genetically identical
      patients with HCM. PATIENTS AND METHODS: Polymorphisms of five RAAS components
      were determined in 26 gene carriers from a single family with HCM caused by a
      previously identified myosin binding protein C mutation. Genotypes associated
      with a higher activation status of the RAAS were labelled "pro-LVH genotypes".
      RESULTS: There was a non-biased distribution of pro-LVH genotypes in the gene
      carriers. Those without pro-LVH genotypes did not manifest cardiac hypertrophy
      whereas gene carriers with pro-LVH genotypes did (mean (SD) left ventricular
      muscle mass 190 (48) v 320 (113), p = 0.002; interventricular septal thickness
      11.5 (2.0) v 16.4 (6.7), p = 0.01; pathological ECG 0% (0 of 10) v 63% (10 of
      16), respectively). Multivariate analysis controlling for age, sex, and
      hypertension confirmed an independent association between the presence of pro-LVH
      polymorphisms and left ventricular mass. When each polymorphism was assessed
      individually, carriers of each pro-LVH genotype had a significantly greater left
      ventricular mass than those with no pro-LVH mutation; these associations, with
      the exception of cardiac chymase A AA polymorphism (p = 0.06), remained
      significant in multivariate analysis. CONCLUSION: Genetic polymorphisms of the
      RAAS influence penetrance and degree of LVH in 26 gene carriers from one family
      with HCM caused by a myosin binding protein C mutation.

PMID- 11847172
TI  - Replacement of extracted permanent pacemaker or defibrillator leads by
      cannulation of veins using the femoral "drag through" technique.

PMID- 11847173
TI  - Images in cardiology. Unroofed coronary sinus.

PMID- 11847174
TI  - Images in cardiology. Thoraco-omphalagus twins: heart to heart.

PMID- 11847175
TI  - Khat chewing and acute myocardial infarction.

PMID- 11847177
TI  - Angiogenesis in chronically ischaemic human heart following percutaneous
      myocardial revascularisation.

PMID- 11847178
TI  - Images in cardiology. Microscopic evidence of effective ablation of calcium and
      metal from coronary arteries treated with directional coronary atherectomy using
      the Flexicut device.

PMID- 11847179
TI  - Myocardial molecular biology: an introduction.

PMID- 11847180
TI  - The need for palliative care in the management of heart failure.

PMID- 11847181
TI  - Which patient should be referred to an electrophysiologist: supraventricular
      tachycardia.

PMID- 11847183
TI  - Association between pulse pressure and C-reactive protein among apparently
      healthy US adults.
AB  - Elevated pulse pressure has been associated with an increased risk of
      cardiovascular disease, which is increasingly being seen as an inflammatory
      disease. Thus, the mechanism underlying the link between elevated pulse pressure
      and cardiovascular disease risk may be inflammation. However, investigators have
      not examined the relationship between pulse pressure and C-reactive protein, an
      inflammation marker that has been closely linked to cardiovascular risk. We
      examined the cross-sectional relationship between pulse pressure and C-reactive
      protein among 9867 healthy persons 17 years of age or older who participated in
      the Third National Health and Nutrition Examination Survey. The association
      between pulse pressure and the odds of having an elevated C-reactive protein
      level (> or = 0.66 mg/dL) was assessed by logistic regression. In a model that
      adjusted for systolic blood pressure, demographic factors, cholesterol, measures
      of obesity, smoking, alcohol consumption, physical activity, and antihypertensive
      medication use, a 10 mm Hg increase in pulse pressure was associated with a 15%
      increase in the odds of having an elevated C-reactive protein level (odds ratio,
      1.15; 95% confidence interval, 1.01 to 1.31; P=0.04). When the same model was re
      run adjusting for diastolic blood pressure instead of systolic blood pressure, a
      10 mm Hg rise in pulse pressure was associated with a significant 12% increase in
      the odds of having an elevated C-reactive protein level. Systolic and diastolic
      blood pressure were unrelated to C-reactive protein once pulse pressure had been
      accounted for. Our results suggest that increases in pulse pressure are
      associated with elevated C-reactive protein levels among apparently healthy US
      adults, independent of systolic and diastolic blood pressure.

PMID- 11847182
TI  - Low-renin hypertension, altered sodium homeostasis, and an alpha-adducin
      polymorphism.
AB  - Defining the genetic basis of common forms of human essential hypertension is
      most informative when correlated with physiological mechanisms that underlie
      blood pressure regulation. A polymorphism of the alpha-adducin gene as been
      associated with elevated blood pressure in the rat, but previous studies of the
      460Trp polymorphism of the human alpha-adducin gene have not clearly identified
      an association with hypertension. In this study, the frequency of the 460Trp
      allele was 19% and 9 of 279 subjects (3.2%) were homozygous for the 460Trp
      allele. The systolic blood pressure response to changes in dietary sodium was
      significantly greater in subjects homozygous for the 460Trp allele (25 +/- 4 mm
      Hg) compared with subjects heterozygous for 460Trp (12 +/- 2 mm Hg) or homozygous
      for the 460Gly allele (14 +/- 1 mm Hg). Intracellular erythrocyte sodium content,
      sodium-lithium countertransport, and renal fractional excretion of sodium were
      significantly decreased in subjects homozygous for the 460Trp polymorphism
      (P<0.05). There was a significant association between homozygosity for the 460Trp
      allele and low-renin hypertension. Subjects heterozygous for the 460Trp allele
      did not have increased salt-sensitivity or an increased frequency of low-renin
      hypertension. Therefore, this study demonstrates a common genetic basis for
      altered cellular sodium homeostasis, impaired renal sodium handling, and salt
      sensitivity of systolic blood pressure in individuals homozygous for the 460Trp
      polymorphism of the alpha-adducin gene. Homozygosity for this alpha-adducin
      allele may be an important determinant for approximately 10% of individuals with
      low-renin hypertension.

PMID- 11847184
TI  - Prevalence of hypertension in Hispanic and non-Hispanic white populations.
AB  - Mexican nationals in Mexico City and Mexican Americans in San Antonio, Tex, have
      a lower adjusted prevalence of hypertension than San Antonio non-Hispanic whites,
      especially after adjusting for the greater obesity of San Antonio Mexican
      Americans. The concomitant examination of a new study from Spain may better
      explain the association of genetic and environmental factors with hypertension.
      Three population-based epidemiological studies conducted in Mexico City, Spain,
      and San Antonio, Tex, were available for comparisons. Hypertension was defined as
      systolic blood pressure > or = 140 mm Hg, diastolic blood pressure > or = 90 mm
      Hg, or the use of antihypertensive medications. The prevalence of hypertension
      was independently associated with age, body mass index, glucose tolerance, and
      alcohol consumption, with comparable degrees of relationship in all 4
      populations. Relative to San Antonio non-Hispanic whites, an excess prevalence of
      hypertension was observed in Spaniards (odds ratio [OR], 1.53; 95% confidence
      interval [95% CI], 1.24 to 1.90). A deficit in hypertension prevalence was
      statistically significant in Mexican nationals (OR, 0.67; 95% CI, 0.53 to 0.85)
      and close to significance in San Antonio Mexican Americans (OR, 0.86; 95% CI,
      0.71 to 1.03). Thus, obesity, educational attainment, type 2 diabetes, glucose
      tolerance, and marked alcohol consumption (> or = 14 drinks/wk) do not fully
      explain the increased prevalence of hypertension in Spain and the lower
      prevalence of hypertension in Mexican-origin populations. Although we cannot
      conclude definitively that these differences are genetically driven, our results
      suggest no relationship between Spanish genetic admixture and the deficit in
      hypertension prevalence in Mexican-origin populations.

PMID- 11847185
TI  - Preproendothelin-1 gene polymorphism is related to a change in vascular
      reactivity in the human mammary artery in vitro.
AB  - A gene polymorphism of preproendothelin-1 (a G-to-T transversion that predicts a
      Lys/Asn change at codon 198) associated with an increased risk of hypertension
      has been recently described in patients carrying the T allele. No study has yet
      determined the impact of this polymorphism on vascular reactivity, although a
      functional role for endothelin-1 in the pathophysiology of hypertension has been
      clarified. At subthreshold concentrations, endothelin-1 and angiotensin II induce
      a potentiation of alpha-adrenergic-dependent vascular tone caused by an increased
      sensitivity of the contractile apparatus to calcium. We investigated
      phenylephrine-induced tone and its amplification by endothelin-1 and angiotensin
      II in human mammary artery rings in vitro. Contractions to phenylephrine (0.1 to
      100 micromol) and endothelin-1 (0.1 to 300 nmol) were not significantly different
      in rings from GT/TT (n=27) and GG (n=21) patients. A subthreshold concentration
      of endothelin-1 (10 pmol) potentiated a phenylephrine-induced contraction (eg, 44
      +/- 12% increase in tone with phenylephrine 1 micromol/L, P<0.001) that was
      significantly higher in the GT/TT group than in the GG group (eg, 44 +/- 12%
      versus 82 +/- 11%, P<0.01). A similar effect on response to phenylephrine was
      observed with a subthreshold concentration of angiotensin II. We also found a
      higher response to calcium in arteries from GT/TT patients. Endothelium-dependent
      or -independent relaxations were unaffected by the genotype. These data suggest
      that the preproendothelin-1 gene polymorphism is associated with a higher
      potentiating effect of endothelin-1 and angiotensin II, probably in relation with
      higher calcium sensitivity. These changes in vascular reactivity might help to
      understand the relations between this polymorphism and cardiovascular disorders.

PMID- 11847186
TI  - Blood pressure and NaCl-sensitive hypertension are influenced by angiotensin
      converting enzyme gene expression in transgenic mice.
AB  - ACE plays an important role in the regulation of arterial pressure; however, a
      linear relationship between ACE expression and arterial pressure has not been
      demonstrated. The present study employed telemetric monitoring in female
      transgenic mice to determine the influence of partial and complete deletion of
      the ACE gene on basal arterial pressure and arterial pressure responses to a high
      NaCl diet. On the basal NaCl diet, 24-hour mean arterial pressure was
      significantly correlated with the number of functional copies of the ACE gene;
      ie, arterial pressure was lowest in 0-copy (80 +/- 1 mm Hg), intermediate in 1
      copy (100 +/- 1 mm Hg), and highest in 2-copy (113 +/- 1 mm Hg) ACE mice. The
      high-NaCl diet significantly increased mean arterial pressure in 0-copy (99 +/- 1
      mm Hg) and 1-copy (108 +/- 1 mm Hg) mice but not in 2-copy mice (114 +/- 1 mm
      Hg). These results demonstrate a copy-dependent relationship between ACE gene
      expression and both basal arterial pressure and arterial pressure responses to a
      high-NaCl diet, suggesting that either partial or complete reduction in the ACE
      gene can alter arterial pressure.

PMID- 11847187
TI  - Expression of human angiotensinogen-renin in rat: effects on transcription and
      heart function.
AB  - In double transgenic rats (dTGR) harboring the human angiotensinogen (hAOGEN) and
      human renin (hREN) genes, we studied cardiac transcript levels of hypertrophy
      related, Ca(2+) regulatory, and beta-adrenoceptor-associated proteins. The
      contractile properties and the cellular signaling of isolated hearts exposed to (
      )isoproterenol and/or angiotensin (Ang) I were evaluated. dTGR developed
      hypertension of 174.1+/- 7.6 versus 109.6 +/- 2.0 mm Hg (P<0.05) in Sprague
      Dawley rats and heart hypertrophy. In hearts of dTGR, the transcript levels of
      ANP, beta-MHC, and alpha-MHC were altered (percentage versus Sprague-Dawley rats,
      100%) by 304%, 178%, and 78%, respectively. Transcript levels of L-type Ca(2+)
      channel, Ca(2+) release channel, SERCA2a, phospholamban, G(i)- and G(s)-proteins
      were unchanged. Isolated hearts of dTGR indicated higher baseline contractility
      versus Sprague-Dawley rats. (-)Isoproterenol-modified contractility occurred in
      both groups; however, the extent (predrug value, 100%) was less in hearts of dTGR
      versus Sprague-Dawley rats (+dP/dt, 310 +/- 42% versus 534 +/- 63%; P<0.05).
      Interestingly, (-)isoproterenol shortened the relaxation time by equivalent to
      25% in both groups. This finding was reflected by a protein kinase A-related
      phospholamban phosphorylation. Ang I depressed the heart contractility but did
      not interact with the protein kinase A pathway. In conclusion, we have found that
      expression of the hAOGEN-hREN complex in dTGR elicited specific effects on
      transcripts of ANP and myofibrillar proteins. Although the beta-adrenergically
      mediated relaxation was not impaired in the hypertrophied hearts, the extent of
      beta-adrenergic inotropic responsiveness was reduced.

PMID- 11847188
TI  - Angiotensinogen and its cleaved derivatives inhibit angiogenesis.
AB  - The members of the serine protease inhibitor (serpin) family, which share a
      common tertiary structure and a role as serin protease inhibitors, are involved
      in a variety of newly discovered functions. For example, antithrombin III exerts
      a strong antiangiogenic activity. Angiotensinogen, the renin substrate, has a
      folded structure and is a member of the noninhibitory serpin subfamily. Two other
      noninhibitory serpins, maspin and pigment epithelium-derived factor, have
      antiangiogenic properties. We investigated the antiangiogenic effect of
      angiotensinogen and 2 related compounds: (1) des(angiotensin I)angiotensinogen,
      the product of angiotensinogen cleavage by renin, and (2) the reactive center
      loop-cleaved angiotensinogen, which is produced after selective and limited
      proteolysis by the protease V8. We used well-established in vitro (endothelial
      cell proliferation and migration, and capillary-like tube formation on Matrigel)
      and in vivo (the chick chorioallantoic membrane assay) models of angiogenesis to
      evaluate the antiangiogenic activities of these 3 related molecules. Our data
      demonstrated that these compounds exerted a clear and equipotent antiangiogenic
      effect, thus attributing a novel function to angiotensinogen and des(angiotensin
      I)angiotensinogen, for which no function was previously known.

PMID- 11847189
TI  - Tonin and kallikrein in the brain of transgenic rat line expressing human tissue
      kallikrein.
AB  - A transgenic rat line harboring the human tissue kallikrein gene was investigated
      for expression and activity of tonin and kallikrein in different regions of the
      brain. The introduction of the transgene into the rat genome produced a
      significant augmentation of the expression levels and activity of rat tissue
      kallikrein. The possibility that human kallikrein does not hydrolyze the rat
      substrate is probably responsible for the augmented expression of the rat enzyme.
      On the other hand, although expression of tonin was significantly reduced, tonin
      activity was not altered in most brain structures, except for cerebellum and
      neurohypophysis.

PMID- 11847190
TI  - Integrins play a critical role in mechanical stress-induced p38 MAPK activation.
AB  - Mechanical stress activates various hypertrophic responses, including activation
      of mitogen-activated protein kinases (MAPKs) in cardiac myocytes. Stretch
      activated extracellular signal-regulated kinases partly through secreted humoral
      growth factors, including angiotensin II, whereas stretch-induced activation of c
      Jun NH(2)-terminal kinases and p38 MAPK was independent of angiotensin II. In
      this study, we examined the role of integrin signaling in stretch-induced
      activation of p38 MAPK in cardiomyocytes of neonatal rats. Overexpression of the
      tumor suppressor PTEN, which inhibits outside-in integrin signaling, strongly
      suppressed stretch-induced activation of p38 MAPK. Overexpression of focal
      adhesion kinase (FAK) antagonized the effects of PTEN, and both tyrosine residues
      at 397 and 925 of FAK were necessary for its effects. Stretch induced tyrosine
      phosphorylation and activation of FAK and Src. Stretch-induced activation of p38
      MAPK was abolished by overexpression of FAT and CSK, which are inhibitors of the
      FAK and Src families, respectively, and was suppressed by overexpression of a
      dominant-negative mutant of Ras. Mechanical stretch-induced increase in protein
      synthesis was suppressed by SB202190, a p38 MAPK inhibitor. These results suggest
      that mechanical stress activates p38 MAPK and induces cardiac hypertrophy through
      the integrin-FAK-Src-Ras pathway in cardiac myocytes.

PMID- 11847191
TI  - Increased dietary salt activates rat aortic endothelium.
AB  - The function of vascular endothelium as a biomechanical sensor permits
      alterations in gene expression in the vascular tree in response to wall stress.
      The present study explored the mechanism by which the arterial endothelium
      responds to changes in dietary salt. Normotensive rats were fed diets containing
      varying amounts of NaCl for 4 days. At that time, levels of phosphorylated p38
      MAP kinase, p42/44 MAP kinase, and p46/54 JNK/SAP kinase increased when the diet
      contained > or = 3.0% NaCl. Kinase assays demonstrated dose-response
      relationships between dietary salt intake and the activities of p38 MAP kinase
      and p42/44 MAP kinase. Aortic segments from animals on the 8.0% NaCl diet
      produced greater amounts of total and active transforming growth factor-beta 1
      (TGF-beta1) and nitric oxide. The MEK1 inhibitor, PD-098059, and the p38 MAP
      kinase inhibitor, SB-203580, decreased production of these bioactive compounds to
      background levels. Intravenous injection of tetraethylammonium chloride (TEA)
      into rats on the 8.0% NaCl diet decreased the activities of p38 MAP kinase and
      p42/44 MAP kinase, compared with rats on the same diet and given vehicle
      intravenously. These findings provided direct evidence that dietary salt
      modulated gene expression in the arterial wall through a tetraethylammonium
      sensitive mechanism and activation of the p38 and p42/44 MAP kinase pathways.

PMID- 11847192
TI  - Important role of Rho-kinase in the pathogenesis of cardiovascular inflammation
      and remodeling induced by long-term blockade of nitric oxide synthesis in rats.
AB  - Chronic inhibition of endothelial NO synthesis by the administration of N(G)
      nitro-L-arginine methyl ester (L-NAME) to rats induces early vascular
      inflammation (monocyte infiltration into coronary vessels and monocyte
      chemoattractant protein-1 expression) as well as subsequent arteriosclerosis. The
      small GTPase Rho controls cell adhesion, motility, and proliferation and is
      activated by several growth factors such as angiotensin II. We investigated the
      effect of a specific inhibitor of Rho-kinase, Y-27632, in rats treated with L
      NAME to determine the role of the Rho/Rho-kinase pathway in the development of
      arteriosclerosis. We found here increased activity of Rho/Rho-kinase after L-NAME
      administration and its prevention by angiotensin II type 1 receptor blockade.
      Hydralazine or lecithinized superoxide dismutase (l-SOD) did not affect Rho/Rho
      kinase activity. Co-treatment with Y-27632 did not affect the L-NAME-induced
      increase in cardiovascular tissue ACE activity or L-NAME-induced decrease in
      plasma NO concentrations, but did prevent the L-NAME-induced early inflammation
      and late coronary arteriosclerosis. In addition, Y-27632 prevented the increased
      gene expression of monocyte chemoattractant protein-1 and transforming growth
      factor-beta1 as well as cardiac fibrosis and glomerulosclerosis. These findings
      suggest that increased activity of Rho/Rho-kinase pathway mediated via the
      angiotensin II type 1 receptor may thus be important in the pathogenesis of early
      vascular inflammation and late remodeling induced by chronic inhibition of NO
      synthesis. The beneficial effects of Rho-kinase inhibition are not mediated by
      restoration of NO production. The Rho-kinase pathway could be a new therapeutic
      target for treatment of vascular diseases.

PMID- 11847194
TI  - Stimulation of collagen production by transforming growth factor-beta1 during
      differentiation of cardiac fibroblasts to myofibroblasts.
AB  - The aim of the present study was to elucidate how transforming growth factor
      beta(1) (TGF-beta(1)) can stimulate collagen deposition in cardiac tissue by
      interstitial cells via stimulation of fibroblasts, via myofibroblasts, or via
      differentiation of fibroblasts to myofibroblasts. The dose- and time-dependent
      stimulation of collagen production and of expression of alpha-smooth muscle actin
      (alpha-SMA), a marker of myofibroblasts, was studied in cultures of second
      passage adult rat cardiac fibroblasts. The TGF-beta(1)-stimulated collagen
      production is positively correlated (r=0.68, P<0.001) with the appearance of
      alpha-SMA. Only at high concentrations (40 to 600 pmol/L) and after a long time
      (24 to 48 hours) of incubation, TGF-beta(1) increases the collagen production and
      stimulates the differentiation of fibroblasts to myofibroblasts. The maximal
      stimulation of the collagen production (2-fold, P<0.001) observed after
      incubation of cultures of fibroblasts with 600 pmol/L TGF-beta(1) for 48 hours is
      accompanied by a maximal stimulation of alpha-SMA expression (3.5-fold, P<0.001),
      when cultures consist mainly of myofibroblasts. The stimulation of collagen
      production cannot be reversed either after additional incubation of TGF-beta(1)
      stimulated second-passage cultures for 2 days or in their offspring in the next
      third passage after incubation for 7 days without TGF-beta(1). The increased
      collagen production in these third-passage cultures cannot be further stimulated
      by TGF-beta(1). Our data suggest that TGF-beta(1)-stimulated collagen production
      in cultures of adult rat cardiac ventricular fibroblasts cannot be explained by a
      direct stimulation of the collagen production either in fibroblasts or in
      myofibroblasts. Instead, TGF-beta(1) induces the differentiation of fibroblasts
      to myofibroblasts, which have a higher activity for collagen production than
      fibroblasts.

PMID- 11847193
TI  - CB(1) receptor antagonist SR141716A inhibits Ca(2+)-induced relaxation in CB(1)
      receptor-deficient mice.
AB  - Mesenteric branch arteries isolated from cannabinoid type 1 receptor knockout
      (CB(1)(-/-)) mice, their wild-type littermates (CB(1)(+/+) mice), and C57BL/J
      wild-type mice were studied to test the hypothesis that murine arteries undergo
      high sensitivity Ca(2+)-induced relaxation that is CB(1) receptor dependent.
      Confocal microscope analysis of mesenteric branch arteries from wild-type mice
      showed the presence of Ca(2+) receptor-positive periadventitial nerves. Arterial
      segments of C57 control mice mounted on wire myographs contracted in response to
      5 micromol/L norepinephrine and responded to the cumulative addition of
      extracellular Ca(2+) with a concentration-dependent relaxation that reached a
      maximum of 72.0 +/- 6.3% of the prerelaxation tone and had an EC(50) for Ca(2+)
      of 2.90 +/- 0.54 mmol/L. The relaxation was antagonized by precontraction in
      buffer containing 100 mmol/L K(+) and by pretreatment with 10 mmol/L
      tetraethylammonium. Arteries from CB(1)(-/-) and CB(1)(+/+) mice also relaxed in
      response to extracellular Ca(2+) with no differences being detected between the
      knockout and their littermate controls. SR141716A, a selective CB(1) antagonist,
      caused concentration-dependent inhibition of Ca(2+)-induced relaxation in both
      the knockout and wild-type strains (60% inhibition at 1 micromol/L). O-1918, a
      cannabidiol analog, had a similar blocking effect in arteries of both wild-type
      and CB(1)(-/-) mice at 10 micromol/L. In contrast, 1 micromol/L SR144538, a
      cannabinoid type 2 receptor antagonist, or 50 micromol/L 18alpha-glycyrrhetinic
      acid, a gap junction blocker, were without effect. SR141716A (1 to 30 micromol/L)
      was also assessed for nonspecific actions on whole-cell K(+) currents in isolated
      vascular smooth muscle cells. SR141716A inhibited macroscopic K(+) currents at
      concentrations higher than those required to inhibit Ca(2+)-induced relaxation,
      and appeared to have little effect on currents through large conductance Ca(2+)
      activated K(+) channels. These data indicate that arteries of the mouse relax in
      response to cumulative addition of extracellular Ca(2+) in a hyperpolarization
      dependent manner and rule out a role for CB(1) or CB(2) receptors in this effect.
      The possible role of a nonclassical cannabinoid receptor is discussed.

PMID- 11847195
TI  - Cardiovascular effects of overexpression of endothelial nitric oxide synthase in
      the rostral ventrolateral medulla in stroke-prone spontaneously hypertensive
      rats.
AB  - We have previously demonstrated that the overexpression of endothelial NO
      synthase (eNOS) in the rostral ventrolateral medulla (RVLM) decreases blood
      pressure, heart rate, and sympathetic nerve activity via an increase in gamma
      amino butyric acid release in normotensive Wistar-Kyoto rats (WKY). Stroke-prone
      spontaneously hypertensive rats (SHRSP) appear to have reductions of NO
      production and GABA release in the RVLM. The aim of this study was to determine
      whether the effects of the increase in NO production in the RVLM in SHRSP are
      different from those in WKY. We transfected adenovirus vectors encoding either
      eNOS (AdeNOS) or beta-galactosidase (Adbetagal) into the RVLM of both strains. In
      the AdeNOS-treated group, mean arterial blood pressure and heart rate in the
      conscious state were significantly decreased at day 7 after the gene transfer in
      both strains. The decreases in mean arterial blood pressure and heart rate were
      significantly greater in SHRSP than in WKY. Urinary norepinephrine excretion was
      also decreased to a greater degree in SHRSP than in WKY after the gene transfer.
      The pressor response evoked by bicuculline into the RVLM of WKY was greater than
      that of SHRSP in the nontransfected group. However, in the AdeNOS-treated group,
      the pressor response did not differ between SHRSP and WKY after the gene
      transfer. These results indicate that the increase in NO production evoked by the
      overexpression of eNOS in the RVLM causes greater depressor and
      sympathoinhibitory responses in SHRSP than in WKY by improving an inhibitory
      action of GABA on the RVLM neurons.

PMID- 11847196
TI  - Expression and cellular localization of classic NADPH oxidase subunits in the
      spontaneously hypertensive rat kidney.
AB  - Phagocytes generate superoxide anion (O(2)(-)) by a classic, 5-component NADPH
      oxidase. O(2)(-) contributes to hypertension in spontaneously hypertensive rats
      (SHR). Therefore, we tested the hypothesis that NADPH oxidase expression is
      enhanced in the SHR kidney. We also analyzed the localization of NADPH oxidase
      components in SHR kidney. Renal NADPH oxidase was quantified by reverse
      transcription-polymerase chain reaction and Western blotting and was localized in
      SHR and Wistar Kyoto rat (WKY) kidney by immunohistochemistry. The mRNA for 5
      subunits of phagocyte NADPH oxidase, and also for MOX1 and RENOX (NOX4), was
      detected in adult rat kidney. Kidneys of adult (10 weeks old) SHR had a
      significantly (P<0.01) greater mRNA for p47phox (SHR 0.81 +/- 0.05 versus WKY
      0.37 +/- 0.01, arbitrary unit), which was confirmed by Western blotting (SHR 0.58
      +/- 0.04 versus WKY 0.42 +/- 0.04, arbitrary unit; P<0.05) and by
      immunohistochemistry. This higher p47phox protein expression was also detected in
      young prehypertensive SHR (SHR 0.61 +/- 0.05 versus WKY 0.39 +/- 0.04, arbitrary
      unit; P<0.01). The 10-week-old SHR contained more modest but significantly
      (P<0.05) greater protein for p67phox (SHR 0.54 +/- 0.02 versus WKY 0.46 +/-
      0.02). Immunostaining localized p47phox, p67phox, and p22phox in vasculature,
      macula densa, distal convoluted tubule, cortical collecting duct, and outer and
      inner medullary collecting ducts. The kidney of SHR expresses genes for all the
      main components of phagocyte NADPH oxidase, RENOX, and MOX1. There is a prominent
      increase in the SHR kidney of the mRNA, and protein expression of p47phox in the
      vasculature, macula densa, and distal nephron, which precedes development of
      hypertension.

PMID- 11847197
TI  - Inhibition of the hypothalamic paraventricular nucleus in spontaneously
      hypertensive rats dramatically reduces sympathetic vasomotor tone.
AB  - Experimental evidence indicates that the hypothalamic paraventricular nucleus
      modulates sympathetic vasomotor tone and blood pressure and that this modulation
      is altered in some cardiovascular diseases. This study tested the hypothesis that
      this nucleus exerts a more significant tonic excitatory modulation of basal
      sympathetic vasomotor activity in spontaneously hypertensive rats. In
      anesthetized, artificially-ventilated rats, bilateral microinjections of the
      GABA(A) receptor agonist, muscimol (1 to 1.5 nmoles per side), into the
      paraventricular nucleus produced a depressor and sympathoinhibitory response that
      did not recover. When compared with normotensive rats, this response was more
      marked in spontaneously hypertensive rats, where lumbar sympathetic nerve
      discharge was reduced by 75 +/- 3% and mean arterial pressure fell from 119 +/- 7
      mm Hg to 58 +/- 3 mm Hg. Blockade of excitatory and inhibitory amino acid
      receptors in the rostral ventrolateral medulla significantly attenuated this
      response. Microinjections of small volumes (<20 nL) of GABA were used to localize
      precisely the responsive region of the paraventricular nucleus. Unilateral
      injections of GABA into the dorsomedial cap of the paraventricular nucleus
      induced a brisk depressor (decrease of 42 +/- 4 mm Hg), sympathoinhibitory
      (decrease by 72 +/- 2%), and bradycardic (decrease of 77 +/- 16 bpm) response.
      The mechanisms underlying the sympathoinhibition after inactivation of the
      paraventricular nucleus are not elucidated, but evidence discussed suggests the
      involvement of a supracollicular sympathoinhibitory pathway. The results
      presented demonstrate that the paraventricular nucleus exerts a powerful, tonic
      effect on the control of sympathetic vasomotor tone under basal conditions in
      anesthetized rats and that this is enhanced in spontaneously hypertensive rats.

PMID- 11847198
TI  - Albuminuria in hypertension is linked to altered lysosomal activity and TGF-beta1
      expression.
AB  - Increased intraglomerular pressure is considered a major factor for increased
      albumin excretion in hypertension. However, other factors should also be
      considered because recent studies in both humans and rats have demonstrated that
      proteins undergoing filtration and renal passage are extensively modified by
      renal cell lysosomal processing; >95% of albumin is degraded to peptides that are
      not detected by routine immunochemical assays. Changes in postglomerular
      lysosomal processing may therefore be responsible for the increased intact
      albumin excreted in hypertension-related kidney disease. We hypothesize that
      transforming growth factor-beta, which is known to decrease lysosomal activity,
      may be upregulated in hypertension and may play a role in increased intact
      albumin excretion. The aims of this study were to determine the effect that
      hypertension has on (1) renal cell lysosomal processing of albumin and dextran
      sulfate, (2) glomerular permeability, and (3) renal transforming growth factor
      beta(1) expression. Spontaneously hypertensive rats and Wistar-Kyoto rats were
      used at 8, 16, and 24 weeks. We demonstrate that albuminuria in hypertension is
      linked to an inhibition of lysosomal processing as determined by (1) size
      exclusion chromatography analysis of urinary [(14)C]albumin structural integrity
      and (2) ion exchange analysis of urinary [(3)H]dextran sulfate. This inhibition
      gives rise to an increased proportion of radioimmunoassay detectable (intact)
      albumin and intact dextran sulfate independent of changes in glomerular capillary
      wall permeability as determined by the fractional clearance of [(3)H]Ficolls of
      various radii. These changes may be correlated with increased renal transforming
      growth factor-beta(1) expression.

PMID- 11847199
TI  - Cationic amino acid transport in the renal medulla and blood pressure regulation.
AB  - Previous studies have indicated that NO synthesis in isolated inner medullary
      collecting duct cells is reduced by cationic amino acids that compete with L
      arginine for cellular uptake. In the present study, we investigated the effects
      of chronic renal medullary infusion of cationic amino acids on renal NO
      concentration and mean arterial pressure (MAP) in Sprague-Dawley rats. Renal
      medullary infusion of L-ornithine (50 microg/kg per min) or L-lysine (50
      microg/kg per min) markedly decreased NO in the medulla (vehicle, 124 +/- 11
      nmol/L; L-ornithine, 45 +/- 4 nmol/L; L-lysine, 42 +/- 6 nmol/L) and increased
      MAP (vehicle, 111 +/- 7 mm Hg; L-ornithine, 143 +/- 6 mm Hg; L-lysine, 148 +/- 3
      mm Hg) after 5 days of infusion. In contrast, intravenous infusion of the same
      dose of L-ornithine or L-lysine for 5 days increased plasma concentration to
      levels similar to those observed with intramedullary infusion but did not change
      NO in the medulla or alter MAP. Furthermore, the NO-suppressing and hypertensive
      effects of medullary interstitial infusion of L-ornithine (50 microg/kg per min)
      were attenuated by simultaneous infusion of L-arginine (500 microg/kg per min;
      NO, 97 +/- 10 nmol/L; MAP, 124 +/- 3 mm Hg). A 5-day infusion of an antisense
      oligonucleotide against CAT-1 (18-mer, 8.3 nmol/h) significantly decreased CAT-1
      protein in the medulla, decreased NO in the medulla (scrambled oligo, 124 +/- 10
      nmol/L; antisense oligo, 67 +/- 11 nmol/L), and increased MAP (scrambled oligo,
      113 +/- 2 mm Hg; antisense oligo, 130 +/- 2 mm Hg). These results suggest that
      uptake of L-arginine by cationic amino acid transport systems in the renal
      medulla plays an important role in the regulation of medullary NO and MAP in
      rats.

PMID- 11847200
TI  - Nitric oxide blockade enhances renal responses to superoxide dismutase inhibition
      in dogs.
AB  - To examine the potential role of superoxide anion (O(2)(-)) and its interaction
      with NO in the regulation of renal hemodynamics and excretory function, we have
      evaluated the renal responses to enhancement in O(2)(-) activity before and
      during NO synthase inhibition in anesthetized dogs (n=6). Intraarterial infusion
      of a superoxide dismutase (SOD) inhibitor, diethyldithiocarbamate (DETC; 0.1 and
      0.5 mg/kg per min) was made to enhance O(2)(-) activity in the kidney. Cortical
      (CBF), medullary (MBF), and total renal blood flow (RBF) responses were assessed
      using laser-Doppler needle flow probes and an electromagnetic flow probe. DETC
      caused dose-dependent changes in renal parameters, which were recovered within 30
      minutes after the termination of DETC infusion. The high-dose infusion of DETC
      for 25 minutes resulted in an increase of 29 +/- 10% in renal vascular resistance
      (control, 35.4 +/- 4.4 mm Hg/mL per min per g) and decreases of 21 +/- 5% in RBF
      (control, 3.5 +/- 0.5 mL/min per g), 20 +/- 5% in CBF, 21 +/- 7% in MBF, 62 +/-
      11% in urine flow (control, 10.5 +/- 2.2 microL/min per g), and 47 +/- 11% in
      sodium excretion (control, 2.1 +/- 0.2 micromol/min per g), without a significant
      change (-10 +/- 6%) in glomerular filtration rate (control, 0.74 +/- 0.09 mL/min
      per g). During NO synthase inhibition with intraarterial administration of nitro
      L-arginine (50 microg/kg per min), the same dose of DETC showed a greater
      increase in renal vascular resistance (73 +/- 15%) and reductions in RBF (39 +/-
      4%), CBF (32 +/- 5%), MBF (34 +/- 6%), urine flow (78 +/- 5%), and sodium
      excretion (67 +/- 0%), with a marked reduction in glomerular filtration rate (59
      +/- 7%). These data indicate that O(2)(-) exerts renal vasoconstriction as well
      as antidiuretic and antinatriuretic effects. These responses are enhanced during
      NO synthase blockade, suggesting that NO serves a renoprotective effect against
      these action of O(2)(-).

PMID- 11847201
TI  - Phorbol diacetate potentiates na(+)-k(+) ATPase inhibition by a putative
      endogenous ligand, marinobufagenin.
AB  - Several vasoconstrictor agents can regulate the phosphorylation status of the
      Na(+)-K(+) ATPase (NKA). We have recently demonstrated that mammalian tissues
      contain an endogenous bufadienolide, digitalis-like alpha(1)-NKA-selective
      ligand, marinobufagenin (MBG). Protein kinase C induces phosphorylation of the
      alpha(1)-NKA isoform, the major isoform in vascular smooth muscle, kidney, and
      heart cells. We hypothesized that protein kinase C-induced phosphorylation of NKA
      can potentiate the effect of endogenous digitalis-like ligands, and that such
      potentiation can occur in an NKA isoform-specific fashion. A protein kinase C
      activator, phorbol 12,13-diacetate (PDA, 50 nmol/L), induced phosphorylation of
      the alpha1-NKA from human mesenteric artery (HMA) sarcolemma and rat kidney but
      not that of the alpha(3)-NKA from rat fetal brain. In HMA sarcolemma, which
      predominantly contains alpha(1)-NKA, PDA (50 nmol/L) potentiated the NKA
      inhibitory effect of MBG at the level of high-affinity binding sites (0.05 +/-
      0.03 nmol/L versus 4.0 +/- 1.7 nmol/L, P<0.05). In contrast, PDA did not affect
      the NKA inhibition by ouabain, an alpha(3)-NKA ligand. In isolated endothelium
      denuded HMA artery rings, 50 nmol/L PDA potentiated the MBG-induced
      vasoconstriction (EC(50), 17 +/- 6 nmol/L versus 150 +/- 40 nmol/L; P<0.01). Our
      results suggest that alpha(1)-isoform-specific NKA inhibition by the endogenous
      digitalis-like ligand, MBG, is substantially enhanced via NKA phosphorylation by
      protein kinase C. Thus, an interaction of protein kinase C-dependent
      phosphorylation and MBG on NKA activity may underlie the synergistic vasoactive
      effects of MBG and other endogenous vasoconstrictors in hypertension.

PMID- 11847202
TI  - Prevention of hypertension, insulin resistance, and oxidative stress by alpha
      lipoic acid.
AB  - The aim of the present study was to investigate whether a dietary supplementation
      of alpha-lipoic acid could prevent blood pressure elevation, insulin resistance,
      and the increase in aorta superoxide anion production in a new experimental model
      of hypertension associated with insulin resistance. Sprague-Dawley rats were
      given 10% D-glucose in their drinking water combined either with a normal chow
      diet or with an alpha-lipoic acid-supplemented diet and were compared with
      control rats during 3 weeks. Oxidative stress was evaluated by measuring the
      aortic superoxide anion production using the lucigenin chemiluminescence method.
      Increases in blood pressure, insulin resistance, and aorta superoxide production
      observed in glucose-fed rats were prevented by the supplementation of the diet
      with lipoic acid. Positive correlations were found between aortic superoxide
      production and blood pressure, between insulin resistance and blood pressure, or
      between superoxide production and insulin resistance. Moreover, a decrease in the
      activity of plasma glutathione peroxidase observed in the glucose-fed rats was
      prevented by lipoic acid treatment. These findings demonstrate that high-glucose
      feeding rapidly induced hypertension and insulin resistance in association with
      the induction of a vascular oxidative stress. The antihypertensive action and the
      prevention of insulin resistance by lipoic acid appears to be associated to its
      antioxidative properties because it prevented the increase in oxidative stress,
      as reflected by the normalization of superoxide anion production in aorta and the
      prevention of the fall in the activity of glutathione peroxidase in the glucose
      fed rats.

PMID- 11847204
TI  - How important is pulse pressure as a predictor of cardiovascular risk?

PMID- 11847205
TI  - Role of aldosterone in the pathogenesis of hypertension.

PMID- 11847206
TI  - Neurobiology of birth weight influence on blood pressure values and variability
      in children and adolescents.

PMID- 11847207
TI  - Questioning the cardioprotective effect of bromocriptine treatment.

PMID- 11847209
TI  - Structural requirements of anticoagulant protein S for its binding to the
      complement regulator C4b-binding protein.
AB  - The vitamin K-dependent anticoagulant protein S binds with high affinity to C4b
      binding protein (C4BP), a regulator of complement. Despite the physiological
      importance of the complex, we have only a patchy view of the C4BP-binding site in
      protein S. Based on phage display experiments, protein S residues 447-460 were
      suggested to form part of the binding site. Several experimental approaches were
      now used to further elucidate the structural requirements for protein S binding
      to C4BP. Peptides comprising residues 447-460, 451-460, or 453-460 of protein S
      were found to inhibit the protein S-C4BP interaction, whereas deletion of
      residues 459-460 from the peptide caused complete loss of inhibition. In
      recombinant protein S, each of residues 447-460 was mutated to Ala, and the
      protein S variants were tested for binding to C4BP. The Y456A mutation reduced
      binding to C4BP approximately 10-fold, and a peptide corresponding to residues
      447-460 of this mutant was less inhibitory than the parent peptide. A further
      decrease in binding was observed using a recombinant variant in which a site for
      N-linked glycosylation was moved from position 458 to 456 (Y456N/N458T). A
      monoclonal antibody (HPSf) selective for free protein S reacted poorly with the
      Y456A variant but reacted efficiently with the other variants. A second antibody,
      HPS 34, which partially inhibited the protein S-C4BP interaction, reacted poorly
      with several of the Ala mutants, suggesting that its epitope was located in the
      451-460 region. Phage display analysis of the HPS 34 antibody further identified
      this region as its epitope. Taken together, our results suggest that residues 453
      460 of protein S form part of a more complex binding site for C4BP. A recently
      developed three-dimensional model of the sex hormone-binding globulin-like region
      of protein S was used to analyze available experimental data.

PMID- 11847210
TI  - The leucine-rich repeat protein PRELP binds perlecan and collagens and may
      function as a basement membrane anchor.
AB  - PRELP (proline arginine-rich end leucine-rich repeat protein) is a heparin
      binding leucine-rich repeat protein in connective tissue extracellular matrix. In
      search of natural ligands and biological functions of this molecule, we found
      that PRELP binds the basement membrane heparan sulfate proteoglycan perlecan.
      Also, recombinant perlecan domains I and V carrying heparan sulfate bound PRELP,
      whereas other domains without glycosaminoglycan substitution did not. Heparin,
      but not chondroitin sulfate, inhibited the interactions. Glycosaminoglycan-free
      recombinant perlecan domain V and mutated domain I did not bind PRELP. The
      dissociation constants of the PRELP-perlecan interactions were in the range of 3
      18 nm as determined by surface plasmon resonance. As expected, truncated PRELP,
      without the heparin-binding domain, did not bind perlecan. Confocal
      immunohistochemistry showed that PRELP outlines basement membranes with a
      location adjacent to perlecan. We also found that PRELP binds collagen type I and
      type II through its leucine-rich repeat domain. Electron microscopy visualized a
      complex with PRELP binding simultaneously to the triple helical region of
      procollagen I and the heparan sulfate chains of perlecan. Based on the location
      of PRELP and its interaction with perlecan heparan sulfate chains and collagen,
      we propose a function of PRELP as a molecule anchoring basement membranes to the
      underlying connective tissue.

PMID- 11847212
TI  - Primary structure of a dynamin-related mouse mitochondrial GTPase and its
      distribution in brain, subcellular localization, and effect on mitochondrial
      morphology.
AB  - A new member of the dynamin GTPase family (OPA1) was recently identified in
      humans and shown to be mutated in patients with dominant optic atrophy. To
      understand better the function of mammalian OPA1, we isolated a mouse ortholog
      (mOPA1) from brain and raised a specific antibody against its C terminus. The
      subcellular distribution of mOPA1 overexpressed in COS-7 cells largely overlapped
      that of endogenous cytochrome c, a well known mitochondrial marker, and
      dramatically affected mitochondrial morphology, altering it from tubular to
      vesicular. Mitochondrial targeting was mediated by the N-terminal region of mOPA1
      as follows: deletion of the 124 N-terminal amino acids eliminated mitochondrial
      targeting, although fusion of the N-terminal 60 or 90 amino acids of mOPA1 with
      green fluorescent protein resulted in its mitochondrial targeting. mOPA1 was
      expressed widely in the mouse brain, especially in neurons of olfactory bulb,
      cerebral cortex, piriform cortex, hypothalamus, hippocampus, red nucleus,
      cochlear nucleus, motor trigeminal nucleus, facial nucleus, cerebellar nucleus,
      and Purkinje cells. Within dissociated cerebellar cells, mOPA1 protein was
      clearly observed in the dendrites and somas of neuronal cells, as well as in
      astrocytes and meningeal cells. In each case, it was distributed in the vesicular
      pattern seen in other cell types.

PMID- 11847211
TI  - c-Cbl associates directly with the C-terminal tail of the receptor for the
      macrophage colony-stimulating factor, c-Fms, and down-modulates this receptor but
      not the viral oncogene v-Fms.
AB  - The receptor for the macrophage colony-stimulating factor (CSF-1, also termed M
      CSF), the tyrosine kinase c-Fms, was originally determined to be the oncogene
      product of the McDonough strain of feline sarcoma virus, v-Fms. The structural
      difference between c-Fms and v-Fms amounts to only five point mutations in the
      extracellular domain, two mutations in the cytoplasmic domain, and the
      replacement of 50 amino acids by 14 unrelated amino acids at the C-terminal tail.
      Here, we have identified c-Cbl as the direct binding partner for c-Fms. c-Cbl
      binds to phosphotyrosine residue 977 at the C-terminal end of feline c-Fms, which
      is absent in v-Fms. The replacement of the C-terminal end of v-Fms by the
      corresponding part of c-Fms (vc-Fms) restored the binding potential. As a result,
      vc-Fms reduced the transforming potency of v-Fms. The overexpression of Cbl did
      not influence the v-Fms-transformed phenotype, although c-Cbl forms a complex
      with v-Fms indirectly. In contrast, the expression of Cbl drastically reduced the
      vc-Fms-transformed phenotype and the activation of Erk and enhanced Fms
      ubiquitination via phosphotyrosine residue 977. Furthermore, the replacement of
      tyrosine 977 into phenylalanine in feline c-Fms and vc-Fms reduced the Cbl
      dependent ubiquitination. These data suggest that an indirect association of c
      Cbl via multimeric complex induced a different signaling pathway from the pathway
      induced by c-Cbl direct interaction.

PMID- 11847213
TI  - Receptor activity-modifying protein 1 determines the species selectivity of non
      peptide CGRP receptor antagonists.
AB  - The heterodimeric CGRP receptor requires co-expression of calcitonin receptor
      like receptor (CRLR) and an accessory protein called receptor activity-modifying
      protein (RAMP) 1 (McLatchie, L. M., Fraser, N. J., Main, M. J., Wise, A., Brown,
      J., Thompson, N., Solari, R., Lee, M. G., and Foord, S. M. (1998) Nature 393, 333
      339). Several non-peptide CGRP receptor antagonists have been shown to exhibit
      marked species selectivity, with >100-fold higher affinities for the human CGRP
      receptor than for receptors from other species (Doods, H., Hallermayer, G., Wu,
      D., Entzeroth, M., Rudolf, K., Engel, W., and Eberlein, W. (2000) Br. J.
      Pharmacol. 129, 420-423; Edvinsson, L., Sams, A., Jansen-Olesen, I., Tajti, J.,
      Kane, S. A., Rutledge, R. Z., Koblan, K. S., Hill, R. G., and Longmore, J. (2001)
      Eur. J. Pharmacol. 415, 39-44). This observation provided an opportunity to map
      the determinants of receptor affinity exhibited by BIBN4096BS and the truncated
      analogs, Compounds 1 and 2. All three compounds exhibited higher affinity for the
      human receptor, human CRLR/human RAMP1, than for the rat receptor, rat CRLR/rat
      RAMP1. We have now demonstrated that this species selectivity was directed
      exclusively by RAMP1. By generating recombinant human/rat CRLR/RAMP1 receptors,
      we demonstrated that co-expression of human CRLR with rat RAMP1 produced rat
      receptor pharmacology, and vice versa. Moreover, with rat/human RAMP1 chimeras
      and site-directed mutants, we have identified a single amino acid at position 74
      of RAMP1 that modulates the affinity of small molecule antagonists for
      CRLR/RAMP1. Replacement of lysine 74 in rat RAMP1 with tryptophan (the homologous
      amino acid in the human receptor) resulted in a > or =100-fold increase in
      antagonist affinities, similar to the K(i) values for the human receptor. These
      observations suggest that important determinants of small molecule antagonist
      affinity for the CGRP receptor reside within the extracellular region of RAMP1
      and provide evidence that this receptor accessory protein may participate in
      antagonist binding.

PMID- 11847214
TI  - Pituitary adenylyl cyclase-activating polypeptide prevents induced cell death in
      retinal tissue through activation of cyclic AMP-dependent protein kinase.
AB  - Multiple neuroactive substances are secreted by neurons and/or glial cells and
      modulate the sensitivity to cell death. In the developing retina, it has been
      shown that increased intracellular levels of cAMP protect cells from
      degeneration. We tested the hypothesis that the neuroactive peptide pituitary
      adenylyl cyclase-activating polypeptide (PACAP) has neuroprotective effects upon
      the developing rat retina. PACAP38 prevented anisomycin-induced cell death in the
      neuroblastic layer (NBL) of retinal explants, and complete inhibition of induced
      cell death was obtained with 1 nm. A similar protective effect was observed with
      PACAP27 and with the specific PAC1 receptor agonist maxadilan but not with
      glucagon. Photoreceptor cell death induced by thapsigargin was also prevented by
      PACAP38. The neuroprotective effect of PACAP38 upon the NBL could be reverted by
      the competitive PACAP receptor antagonist PACAP6-38 and by the specific PAC1
      receptor antagonist Maxd.4. Molecular and immunohistochemical analysis
      demonstrated PAC1 receptors, and treatment with PACAP38 induced phospho-cAMP
      response element-binding protein immunoreactivity in the anisomycin-sensitive
      undifferentiated postmitotic cells within the NBL. PACAP38 produced an increase
      in cAMP but not inositol triphosphate, and treatment with the cAMP-dependent
      protein kinase inhibitor R(p)-cAMPS blocked the protective effect of PACAP38. The
      results indicate that activation of PAC1 receptors by PACAP38 modulates cell
      death in the developing retina through the intracellular cAMP/cAMP-dependent
      protein kinase pathway.

PMID- 11847215
TI  - Neutrophil-derived glutamate regulates vascular endothelial barrier function.
AB  - Endothelial barrier function is altered by the release of soluble
      polymorphonuclear leukocyte (PMN)-derived mediators during inflammatory states.
      However, endogenous pathways to describe such changes are only recently
      appreciated. Using an in vitro endothelial paracellular permeability model, cell
      free supernatants from formylmethionylleucylphenylalanine-stimulated PMNs were
      observed to significantly alter endothelial permeability. Biophysical and
      biochemical analysis of PMN supernatants identified PMN-derived glutamate in
      modulating endothelial permeability. Furthermore, novel expression of
      metabotropic glutamate receptor 1 (mGluR1), mGluR4, and mGluR5 by human brain and
      dermal microvascular endothelial cells was demonstrated by reverse transcription
      PCR, in situ hybridization, immunofluorescence, and Western blot analysis.
      Treatment of human brain endothelia with glutamate or selective, mGluR group I or
      III agonists resulted in a time-dependent loss of phosphorylated vasodilator
      stimulated phosphoprotein (VASP) and significantly increased endothelial
      permeability. Glutamate-induced decreases in brain endothelial barrier function
      and phosphorylated VASP were significantly attenuated by pretreatment of human
      brain endothelia with selective mGluR antagonists. These observations were
      extended to an in vivo hypoxic mouse model in which pretreatment with mGluR
      antagonists significantly decreased fluorescein isothiocyanate-dextran flux
      across the blood-brain barrier. We conclude that activated human PMNs release
      glutamate and that endothelial expression of group I or III mGluRs function to
      decrease human brain endothelial VASP phosphorylation and barrier function. These
      results identify a novel pathway by which PMN-derived glutamate may regulate
      human endothelial barrier function.

PMID- 11847216
TI  - 4E-binding proteins, the suppressors of eukaryotic initiation factor 4E, are down
      regulated in cells with acquired or intrinsic resistance to rapamycin.
AB  - To determine whether inhibition of either the ribosomal p70 S6 kinase or
      eukaryotic initiation factor (eIF) 4E pathways downstream of the mammalian target
      of rapamycin, mTOR, contributes to rapamycin-induced growth arrest, clones of
      Rh30 rhabdomyosarcoma cells were selected for rapamycin resistance. Expression of
      c-Myc and anchorage-independent growth were enhanced in resistant cells.
      Resistance was unstable in each of three clones characterized. In resistant
      cells, as compared with parental cells, approximately 10-fold less 4E-binding
      protein (4E-BP) was bound to eIF4E, and total cellular 4E-BP was markedly
      reduced. Levels of eIF4E were unchanged. Steady-state levels of 4E-BP transcript
      remained unaltered, but the rate of 4E-BP synthesis was reduced in resistant
      cells. In cells that reverted to rapamycin sensitivity, levels of total 4E-BP
      returned to those of parental cells. Compared with parental cells, resistant
      clones had either similar or lower levels and activity of ribosomal p70 S6
      kinase, but c-Myc levels were elevated in both resistant and revertant clones.
      Several colon carcinoma cell lines with intrinsic rapamycin resistance were found
      to have low 4E-BP:eIF4E ratios. In stable clones of HCT8 carcinoma engineered to
      overexpress 4E-BP, rapamycin sensitivity increased markedly (>1000-fold) as 4E-BP
      expression increased. These results suggest that the 4E-BP:eIF4E ratio is an
      important determinant of rapamycin resistance and controls certain aspects of the
      malignant phenotype.

PMID- 11847217
TI  - Structural requirements for potent versus selective cytotoxicity for
      antimicrobial dermaseptin S4 derivatives.
AB  - To better understand the structural requirements for selective cytotoxicity of
      antimicrobial peptides, seven dermaseptin S4 analogs were produced and
      investigated with respect to molecular organization in solution, binding
      properties to model phospholipid membranes, and cytotoxic properties. Native
      dermaseptin S4 displayed high aggregation in solution and high binding affinity.
      These properties correlated with high cytotoxicity. Yet, potency was
      progressively limited when facing cells whose plasma membrane was surrounded by
      increasingly complex barriers. Increasing the positive charge of the native
      peptide led to partial depolymerization that correlated with higher binding
      affinity and with virtually non-discriminative high cytotoxicity against all cell
      types. The C-terminal hydrophobic domain was found responsible for binding to
      membranes but not for their disruption. Truncations of the C terminus combined
      with increased positive charge of the N-terminal domain resulted in short
      peptides having similar binding affinity as the parent compound but displaying
      selective activity against microbes with reduced toxicity toward human red blood
      cells. Nuclear magnetic resonance-derived three-dimensional structures of three
      active derivatives enabled the delineation of a common amphipathic structure with
      a clear separation of two lobes of positive and negative electrostatic potential
      surfaces. Whereas the spatial positive electrostatic potential extended
      considerably beyond the peptide dimensions and was required for potency,
      selectivity was affected primarily by hydrophobicity. The usefulness of this
      approach for the design of potent and/or selective cytolytic peptides is
      discussed herein.

PMID- 11847218
TI  - Beta-secretase processing in the trans-Golgi network preferentially generates
      truncated amyloid species that accumulate in Alzheimer's disease brain.
AB  - The amyloid beta (A beta) peptide that accumulates in Alzheimer's disease brain
      is derived from the proteolytic processing of the amyloid precursor protein by
      beta- and gamma-secretase activities. The beta-secretase enzyme beta-site amyloid
      precursor protein-cleaving enzyme (BACE) generates the N terminus of A beta by
      cleavage at either Asp(1) (beta-site) or Glu(11) (beta'-site), ultimately leading
      to the production of full-length A beta 1-40/42 or truncated A beta 11-40/42. The
      functional significance of this variable cleavage site specificity as well as the
      relative pathological impact of full-length versus N-terminally truncated A beta
      remains largely unknown. In our analysis of BACE reactivity in cell culture, we
      found that the preference of the protease for either beta- or beta'-cleavage was
      strongly dependent on intracellular localization. Within the endoplasmic
      reticulum, beta-site proteolysis predominated, whereas in the trans-Golgi
      network, beta'-cleavage was favored. Furthermore, the contrasting cleavage site
      specificities of BACE were not simply due to differences in organelle pH or the
      oligosaccharide composition of the glycoproteins involved. Examination of post
      mortem brain specimens revealed significant levels of A beta 11-40/42 within
      insoluble amyloid pools. Taken together, these data support an important role for
      beta'-cleavage in the process of cerebral amyloid deposition and localize the
      processing event to the trans-Golgi network.

PMID- 11847220
TI  - The RasGAP N-terminal fragment generated by caspase cleavage protects cells in a
      Ras/PI3K/Akt-dependent manner that does not rely on NFkappa B activation.
AB  - RasGAP, a regulator of Ras GTPase family members, is cleaved at low levels of
      caspase activity into an N-terminal fragment (fragment N) that generates potent
      anti-apoptotic signals. At higher levels of caspase activity, fragment N is
      further cleaved into two fragments that strongly potentiate apoptosis. RasGAP
      could thus function as a sensor of caspase activity to determine whether a cell
      should survive or not. Here we show that fragment N protects cells by activating
      the Ras-PI3K-Akt pathway. Surprisingly, even though nuclear factor kappaB
      (NFkappaB) can be activated by Akt, it plays no role in the anti-apoptotic
      functions of fragment N. This indicates that Akt effectors are differentially
      regulated when fragment N is generated.

PMID- 11847219
TI  - Up-regulation of prostaglandin E2 synthesis by interleukin-1beta in human orbital
      fibroblasts involves coordinate induction of prostaglandin-endoperoxide H
      synthase-2 and glutathione-dependent prostaglandin E2 synthase expression.
AB  - Prostaglandin E(2) (PGE(2)) production involves the activity of a multistep
      biosynthetic pathway. The terminal components of this cascade, two PGE(2)
      synthases (PGES), have very recently been identified as glutathione-dependent
      proteins. cPGES is cytoplasmic, apparently identical to the hsp90 chaperone, p23,
      and associates functionally with prostaglandin-endoperoxide H synthase-1 (PGHS
      1), the constitutive cyclooxygenase. A second synthase, designated mPGES, is
      microsomal and can be regulated. Here we demonstrate that mPGES and PGHS-2 are
      expressed at very low levels in untreated human orbital fibroblasts. Interleukin
      (IL)-1beta treatment elicits high levels of PGHS-2 and mPGES expression. The
      induction of both enzymes occurs at the pretranslational level, is the
      consequence of enhanced gene promoter activities, and can be blocked by
      dexamethasone (10 nm). SC58125, a PGHS-2-selective inhibitor, could attenuate the
      induction of mPGES, suggesting a dependence of this enzyme on PGHS-2 activity. IL
      1beta treatment activates p38 and ERK mitogen-activated protein kinases.
      Induction of both mPGES and PGHS-2 was susceptible to either chemical inhibition
      or molecular interruption of these pathways with dominant negative constructs.
      These results indicate that the induction of PGHS-2 and mPGES by IL-1beta
      underlies robust PGE(2) production in orbital fibroblasts.

PMID- 11847221
TI  - Not all perlecans are created equal: interactions with fibroblast growth factor
      (FGF) 2 and FGF receptors.
AB  - Human basement membrane heparan sulfate proteoglycan (HSPG) perlecan binds and
      activates fibroblast growth factor (FGF)-2 through its heparan sulfate (HS)
      chains. Here we show that perlecans immunopurified from three cellular sources
      possess different HS structures and subsequently different FGF-2 binding and
      activating capabilities. Perlecan isolated from human umbilical arterial
      endothelial cells (HUAEC) and a continuous endothelial cell line (C11 STH) bound
      similar amounts of FGF-2 either alone or complexed with FGFRalpha1-IIIc or
      FGFR3alpha-IIIc. Both perlecans stimulated the growth of BaF3 cell lines
      expressing FGFR1b/c; however, only HUAEC perlecan stimulated those cells
      expressing FGFR3c, suggesting that the source of perlecan confers FGF and FGFR
      binding specificity. Despite these differences in FGF-2 activation, the level of
      2-O- and 6-O-sulfation was similar for both perlecans. Interestingly, perlecan
      isolated from a colon carcinoma cell line that was capable of binding FGF-2 was
      incapable of activating any BaF3 cell line unless the HS was removed from the
      protein core. The HS chains also exhibited greater bioactivity after digestion
      with heparinase III. Collectively, these data clearly demonstrate that the
      bioactivity of HS decorating a single PG is dependent on its cell source and that
      subtle changes in structure including secondary interactions have a profound
      effect on biological activity.

PMID- 11847222
TI  - Guanine nucleotide exchange factor-like factor (Rlf) induces gene expression and
      potentiates alpha 1-adrenergic receptor-induced transcriptional responses in
      neonatal rat ventricular myocytes.
AB  - Expression of constitutively active Ras (V12Ras) in cultured neonatal rat
      ventricular myocytes or targeted cardiac expression of V12Ras in transgenic mice
      induces myocardial cell growth and expression of genes that are markers of
      cardiac hypertrophy including atrial natriuretic factor (ANF) and myosin light
      chain-2. However, the signaling pathways that modulate the effects of Ras on
      acquisition of the various features of cardiac hypertrophy are not known. We
      identified the Ral guanine nucleotide exchange factor-like factor (Rlf) in a
      yeast two-hybrid screen of human heart cDNA library using Ras as bait, suggesting
      that Ras signaling in the heart may involve Rlf. We demonstrate here that Rlf is
      expressed in human heart. Expression of wild type Rlf or Rlf-CAAX, a membrane
      targeted mutant of Rlf, transactivated ANF and myosin light chain-2 promoters but
      did not activate canonical cAMP responsive elements or phorbol ester responsive
      elements, suggesting that Rlf expression does not lead to a generalized increase
      in transcription. Transfection of mutant ANF promoter-reporter gene constructs
      demonstrated that the proximal serum response element is both necessary and
      sufficient for Rlf-inducible ANF expression. Rlf-induced ANF promoter activation
      required Ral and Cdc42 but not RhoA, Rac1, ERK, or p38 kinase activation. In
      addition, Rlf potentiated alpha(1)-adrenergic receptor (alpha(1)-AR)-induced ANF
      expression. Prolonged activation of the alpha(1)-AR increases RalGTP levels in
      neonatal rat ventricular myocytes, further emphasizing a role for Ral guanine
      nucleotide exchange factors in alpha(1)-AR signaling. Overall, this study
      supports the concept that Rlf and Ral are important previously unrecognized
      signaling components that regulate transcriptional responses in myocardial cells.

PMID- 11847223
TI  - Characterization of the in vivo sites of serine phosphorylation on Lck
      identifying serine 59 as a site of mitotic phosphorylation.
AB  - The lymphocyte-specific protein-tyrosine kinase Lck plays a critical role in T
      cell activation. In response to T cell antigen receptor binding Lck undergoes
      phosphorylation on serine residues that include serines 59 and 194. Serine 59 is
      phosphorylated by ERK mitogen-activated protein kinase. Recently, we showed that
      in mitotic T cells Lck becomes hyper-phosphorylated on serine residues. In this
      report, using one-dimensional phosphopeptide mapping analysis, we identify serine
      59 as a site of in vivo mitotic phosphorylation in Lck. The mitotic
      phosphorylation of serine 59 did not require either the catalytic activity or
      functional SH2 or SH3 domains of Lck. In addition, the presence of ZAP-70 also
      was dispensable for the phosphorylation of serine 59. Although previous studies
      demonstrated that serine 59 is a substrate for the ERK MAPK pathway, inhibitors
      of this pathway did not block the mitotic phosphorylation of serine 59. These
      results identify serine 59 as a site of mitotic phosphorylation in Lck and
      suggest that a pathway distinct from that induced by antigen receptor signaling
      is responsible for its phosphorylation. Thus, the phosphorylation of serine 59 is
      the result of two distinct signaling pathways, differentially activated in
      response to the physiological state of the T cell.

PMID- 11847224
TI  - A transmembrane tight junction protein selectively expressed on endothelial cells
      and platelets.
AB  - Searching for cell surface proteins expressed at interendothelial cell contacts,
      we have raised monoclonal antibodies against intact mouse endothelial cells. We
      obtained two monoclonal antibodies, 1G8 and 4C10, that stain endothelial cell
      contacts and recognize a protein of 55 kDa. Purification and identification by
      mass spectrometry of this protein revealed that it contains two extracellular Ig
      domains, reminiscent of the JAM family, but a much longer 120-amino acid
      cytoplasmic domain. The antigen is exclusively expressed on endothelial cells of
      various organs as was analyzed by immunohistochemistry. Immunogold labeling of
      ultrathin sections of brain as well as skeletal muscle revealed that the antigen
      strictly colocalizes in capillaries with the tight junction markers occludin,
      claudin-5, and ZO-1. Upon transfection into MDCK cells, the antigen was
      restricted to the most apical tip of the lateral cell surface, where it
      colocalized with ZO-1 but not with beta-catenin. In contrast to JAM-1, however,
      the 1G8 antigen does not associate with the PDZ domain proteins ZO-1, AF-6, or
      ASIP/PAR-3, despite the presence of a PDZ-binding motif. The 1G8 antigen was not
      detected on peripheral blood mouse leukocytes, whereas similar to JAM-1 it was
      strongly expressed on platelets and megakaryocytes. The 1G8 antigen supports
      homophilic interactions on transfected Chinese hamster ovary cells. Based on the
      similarity to the JAM molecules, it is plausible that the 1G8 antigen might be
      involved in interendothelial cell adhesion.

PMID- 11847225
TI  - A novel cyclophilin from parasitic and free-living nematodes with a unique
      substrate- and drug-binding domain.
AB  - A highly diversified member of the cyclophilin family of peptidyl-prolyl cis
      trans isomerases has been isolated from the human parasite Onchocerca volvulus
      (OvCYP-16). This 25-kDa cyclophilin shares 43-46% similarity to other filarial
      cyclophilins but does not belong to any of the groups previously defined in
      invertebrates or vertebrates. A homolog was also isolated from Caenorhabditis
      elegans (CeCYP-16). Both recombinant O. volvulus and C. elegans cyclophilins were
      found to possess an enzyme activity with similar substrate preference and
      insensitivity to cyclosporin A. They represent novel cyclophilins with important
      differences in the composition of the drug-binding site in particular, namely, a
      Glu(124) (C. elegans) or Asp(123) (O. volvulus) residue present in a critical
      position. Site-directed mutagenesis studies and kinetic characterization
      demonstrated that the single residue dictates the degree of binding to substrate
      and cyclosporin A. CeCYP-16::GFP-expressing lines were generated with expression
      in the anterior and posterior distal portions of the intestine, in all larval
      stages and adults. An exception was found in the dauer stage, where fluorescence
      was observed in both the cell bodies and processes of the ventral chord motor
      neurons but was absent from the intestine. These studies highlight the extensive
      diversification of cyclophilins in an important human parasite and a closely
      related model organism.

PMID- 11847226
TI  - The structural basis of compstatin activity examined by structure-function-based
      design of peptide analogs and NMR.
AB  - We have previously identified compstatin, a 13-residue cyclic peptide, that
      inhibits complement activation by binding to C3 and preventing C3 cleavage to C3a
      and C3b. The structure of compstatin consists of a disulfide bridge and a type I
      beta-turn located at opposite sides to each other. The disulfide bridge is part
      of a hydrophobic cluster, and the beta-turn is part of a polar surface. We
      present the design of compstatin analogs in which we have introduced a series of
      perturbations in key structural elements of their parent peptide, compstatin. We
      have examined the consistency of the structures of the designed analogs compared
      with compstatin using NMR, and we have used the resulting structural information
      to make structure-complement inhibitory activity correlations. We propose the
      following. 1) Even in the absence of the disulfide bridge, a linear analog has a
      propensity for structure formation consistent with a turn of a 3(10)-helix or a
      beta-turn. 2) The type I beta-turn is a necessary but not a sufficient condition
      for activity. 3) Our substitutions outside the type I beta-turn of compstatin
      have altered the turn population but not the turn structure. 4) Flexibility of
      the beta-turn is essential for activity. 5) The type I beta-turn introduces
      reversibility and sufficiently separates the two sides of the peptide, whereas
      the disulfide bridge prevents the termini from drifting apart, thus aiding in the
      formation of the hydrophobic cluster. 6) The hydrophobic cluster at the linked
      termini is involved in binding to C3 and activity but alone is not sufficient for
      activity. 7) beta-Turn residues Gln(5) (Asn(5))-Asp(6)-Trp(7)(Phe(7))-Gly(8) are
      specific for the turn formation, but only Gln(5)(Asn(5))-Asp(6)-Trp(7)-Gly(8)
      residues are specific for activity. 8) Trp(7) is likely to be involved in direct
      interaction with C3, possibly through the formation of a hydrogen bond. Finally
      we propose a binding model for the C3-compstatin complex.

PMID- 11847227
TI  - Functional overlap between retinitis pigmentosa 2 protein and the tubulin
      specific chaperone cofactor C.
AB  - Mutations in the X-linked retinitis pigmentosa 2 gene cause progressive
      degeneration of photoreceptor cells. The retinitis pigmentosa 2 protein (RP2) is
      similar in sequence to the tubulin-specific chaperone cofactor C. Together with
      cofactors D and E, cofactor C stimulates the GTPase activity of native tubulin, a
      reaction regulated by ADP-ribosylation factor-like 2 protein. Here we show that
      in the presence of cofactor D, RP2 protein also stimulates the GTPase activity of
      tubulin. We find that this function is abolished by mutation in an arginine
      residue that is conserved in both cofactor C and RP2. Notably, mutations that
      alter this arginine codon cause familial retinitis pigmentosa. Our data imply
      that this residue acts as an "arginine finger" to trigger the tubulin GTPase
      activity and suggest that loss of this function in RP2 contributes to retinal
      degeneration. We also show that in Saccharomyces cerevisiae, both cofactor C and
      RP2 partially complement the microtubule phenotype resulting from deletion of the
      cofactor C homolog, demonstrating their functional overlap in vivo. Finally, we
      find that RP2 interacts with GTP-bound ADP ribosylation factor-like 3 protein,
      providing a link between RP2 and several retinal-specific proteins, mutations in
      which also cause retinitis pigmentosa.

PMID- 11847229
TI  - Nuclear import and export signals in control of the p53-related protein p73.
AB  - The p53-family of proteins, including p53, p63, and p73, shares a high degree of
      structural similarity and can carry out some redundant functions. However,
      mechanisms that regulate the localization and activity of these proteins have not
      been fully clarified. In this study, a nuclear localization signal (NLS) was
      identified in p73, which is required for p73 nuclear import and which could
      promote the nuclear import of a heterologous, cytoplasmic protein. Mutants
      lacking the NLS localized to the cytoplasm and displayed diminished
      transcriptional activity. A nuclear export signal (NES) was also recognized in
      p73s C terminus, the deletion of which caused p73 to display a more nuclear
      localization pattern. This NES was sensitive to leptomycin B and could function
      as an independent export signal when fused to a heterologous protein.
      Interestingly, p73 mutant proteins lacking the NLS or the NES were more stable
      than wild-type p73, suggesting that nuclear import and nuclear export are
      required for efficient p73 degradation. Our results indicate that p73
      localization is controlled by both nuclear import and export and suggest that the
      overall distribution of p73 is likely to result from the balance between these
      two processes. Proper control of nuclear import and export is likely to be an
      important regulatory determinant of p73.

PMID- 11847228
TI  - Self-assembly of human MxA GTPase into highly ordered dynamin-like oligomers.
AB  - Human MxA protein is a member of the interferon-induced Mx protein family and an
      important component of the innate host defense against RNA viruses. The Mx family
      belongs to a superfamily of large GTPases that also includes the dynamins and the
      interferon-regulated guanylate-binding proteins. A common feature of these large
      GTPases is their ability to form high molecular weight oligomers. Here we
      determined the capacity of MxA to self-assemble into homo-oligomers in vitro. We
      show that recombinant MxA protein assembles into long filamentous structures with
      a diameter of about 20 nm at physiological salt concentration as demonstrated by
      sedimentation assays and electron microscopy. In the presence of guanosine
      nucleotides the filaments rearranged into rings and more compact helical arrays.
      Our data indicate that binding and hydrolysis of GTP induce conformational
      changes in MxA that may be essential for viral target recognition and antiviral
      activity.

PMID- 11847230
TI  - Analysis of the complexity of protein kinases within the phloem sieve tube
      system. Characterization of Cucurbita maxima calmodulin-like domain protein
      kinase 1.
AB  - In angiosperms, functional, mature sieve elements lack nuclei, vacuoles,
      ribosomes, and most of the endomembrane network. In this study, the complexity,
      number, and nature of protein kinases within the phloem sap of Cucurbita maxima
      were investigated to test the hypothesis that the enucleate sieve tube system
      utilizes a simplified signal transduction network. Supporting evidence was
      obtained in that only five putative protein kinases (three calcium-independent
      and two calcium-dependent protein kinases) were detected within the phloem sap
      extracted from stem tissues. Biochemical methods were used to purify one such
      calcium-dependent protein kinase. The gene for this C. maxima calmodulin-like
      domain protein kinase 1 (CmCPK1), was cloned using peptide microsequences. A
      combination of mass spectrometry, peptide fingerprinting, and amino-terminal
      sequencing established that, in the phloem sap, CmCPK1 exists as an amino
      terminally cleaved protein. A second highly homologous isoform, CmCPK2, was
      identified, but although transcripts could be detected in the companion cells,
      peptide fingerprint analysis suggested that CmCPK2 does not enter the phloem sap.
      Potential substrates for CmCPK1, within the phloem sap, were also detected using
      an on-membrane phosphorylation assay. Entry of CmCPK1 into sieve elements via
      plasmodesmata and the potential roles played by these phloem protein kinases are
      discussed.

PMID- 11847231
TI  - Peroxisome proliferator-activated receptor gamma agonists inhibit HIV-1
      replication in macrophages by transcriptional and post-transcriptional effects.
AB  - Previous studies have demonstrated that cyclopentenone prostaglandins (cyPG)
      inhibit human immunodeficiency virus type 1 (HIV-1) replication in various cell
      types. We investigated the role of PG in the replication of HIV-1 in primary
      macrophages. The cyPG, PGA(1) and PGA(2), inhibited HIV-1 replication in acutely
      infected human monocyte-derived macrophages (MDM). Because PGA(1) and PGA(2) have
      previously been shown to be peroxisome proliferator-activated receptor gamma
      (PPARgamma) agonists, we examined the effect of synthetic PPARgamma agonists on
      HIV replication. The PPARgamma agonist ciglitazone inhibited HIV-1 replication in
      a dose-dependent manner in acutely infected human MDM. In addition, cyPG and
      ciglitazone reduced HIV replication in latently infected and viral entry
      independent U1 cells, suggesting an effect at the level of HIV gene expression.
      Ciglitazone also suppressed HIV-1 mRNA levels as measured by reverse
      transcriptase PCR, in parallel with the decrease in reverse transcriptase
      activity. Co-transfection of PPARgamma wild type vectors and treatment with
      PPARgamma agonists inhibited HIV-1 promoter activity in U937 cells. Activation of
      PPARgamma also decreased HIV-1 mRNA stability following actinomycin D treatment.
      In summary, our experimental findings implicate PPARgamma as an important factor
      in the suppression of HIV-1 gene expression in MDM by cyPG. Thus natural and
      synthetic PPARgamma agonists may play a role in controlling HIV-1 infection in
      macrophages.

PMID- 11847232
TI  - Molecular cloning and characterization of CALP/KChIP4, a novel EF-hand protein
      interacting with presenilin 2 and voltage-gated potassium channel subunit Kv4.
AB  - Presenilin (PS) genes linked to early-onset familial Alzheimer's disease encode
      polytopic membrane proteins that are presumed to constitute the catalytic subunit
      of gamma-secretase, forming a high molecular weight complex with other proteins.
      During our attempts to identify binding partners of PS2, we cloned CALP
      (calsenilin-like protein)/KChIP4, a novel member of calsenilin/KChIP protein
      family that interacts with the C-terminal region of PS. Upon co-expression in
      cultured cells, CALP was directly bound to and co-localized with PS2 in
      endoplasmic reticulum. Overexpression of CALP did not affect the metabolism or
      stability of PS complex, and gamma-cleavage of betaAPP or Notch site 3 cleavage
      was not altered. However, co-expression of CALP and a voltage-gated potassium
      channel subunit Kv4.2 reconstituted the features of A-type K(+) currents and CALP
      directly bound Kv4.2, indicating that CALP functions as KChIPs that are known as
      components of native Kv4 channel complex. Taken together, CALP/KChIP4 is a novel
      EF-hand protein interacting with PS as well as with Kv4 that may modulate
      functions of a subset of membrane proteins in brain.

PMID- 11847234
TI  - Interaction of the Rho-ADP-ribosylating C3 exoenzyme with RalA.
AB  - RhoA, -B, and -C are ADP-ribosylated and biologically inactivated by Clostridium
      botulinum C3 exoenzyme and related C3-like transferases. We report that RalA
      GTPase, which is not ADP-ribosylated by C3, inhibits ADP-ribosylation of RhoA by
      C3 from C. botulinum (C3bot), Clostridium limosum (C3lim), and Bacillus cereus
      (C3cer) but not from Staphylococcus aureus (C3stau) in human platelet membranes
      and rat brain lysate. Inhibition by RalA occurs with the GDP- and guanosine 5'-3
      O-(thio)triphosphate-bound forms of RalA and is overcome by increasing
      concentrations of C3. A direct interaction of RalA with C3 was verified by
      precipitation of the transferase with GST-RalA-Sepharose. The affinity constant
      (K(d)) of the binding of RalA to C3lim was 12 nm as determined by fluorescence
      titration. RalA increased the NAD glycohydrolase activity of C3bot by about 5
      fold. Although RalA had no effect on glucosylation of Rho GTPases by Clostridium
      difficile toxin B, C3bot and C3lim inhibited glucosylation of RalA by Clostridium
      sordellii lethal toxin. Furthermore, C3bot decreased activation of phospholipase
      D by RalA. The data indicate that several C3 exoenzymes directly interact with
      RalA without ADP-ribosylating the GTPase. The interaction is of high affinity and
      interferes with essential functions of C3 and RalA.

PMID- 11847233
TI  - Neurodegeneration in methylmalonic aciduria involves inhibition of complex II and
      the tricarboxylic acid cycle, and synergistically acting excitotoxicity.
AB  - Methylmalonic acidurias are biochemically characterized by an accumulation of
      methylmalonate (MMA) and alternative metabolites. There is growing evidence for
      basal ganglia degeneration in these patients. The pathomechanisms involved are
      still unknown, a contribution of toxic organic acids, in particular MMA, has been
      suggested. Here we report that MMA induces neuronal damage in cultures of
      embryonic rat striatal cells at a concentration range encountered in affected
      patients. MMA-induced cell damage was reduced by ionotropic glutamate receptor
      antagonists, antioxidants, and succinate. These results suggest the involvement
      of secondary excitotoxic mechanisms in MMA-induced cell damage. MMA has been
      implicated in inhibition of respiratory chain complex II. However, MMA failed to
      inhibit complex II activity in submitochondrial particles from bovine heart. To
      unravel the mechanism underlying neuronal MMA toxicity, we investigated the
      formation of intracellular metabolites in MMA-loaded striatal neurons. There was
      a time-dependent intracellular increase in malonate, an inhibitor of complex II,
      and 2-methylcitrate, a compound with multiple inhibitory effects on the
      tricarboxylic acid cycle, suggesting their putative implication in MMA
      neurotoxicity. We propose that neuropathogenesis of methylmalonic aciduria may
      involve an inhibition of complex II and the tricarboxylic acid cycle by
      accumulating toxic organic acids, and synergistic secondary excitotoxic
      mechanisms.

PMID- 11847235
TI  - The calmodulin-binding domain of the catalytic gamma subunit of phosphorylase
      kinase interacts with its inhibitory alpha subunit: evidence for a Ca2+ sensitive
      network of quaternary interactions.
AB  - Chemical cross-linking as a probe of conformation has consistently shown that
      activators, including Ca(2+) ions, of the (alphabetagammadelta)(4) phosphorylase
      kinase holoenzyme (PhK) alter the interactions between its regulatory alpha and
      catalytic gamma subunits. The gamma subunit is also known to interact with the
      delta subunit, an endogenous molecule of calmodulin that mediates the activation
      of PhK by Ca(2+) ions. In this study, we have used two-hybrid screening and
      chemical cross-linking to dissect the regulatory quaternary interactions
      involving these subunits. The yeast two-hybrid system indicated that regions near
      the C termini of the gamma (residues 343-386) and alpha (residues 1060-1237)
      subunits interact. The association of this region of alpha with gamma was
      corroborated by the isolation of a cross-linked fragment of alpha containing
      residues 1015-1237 from an alpha-gamma dimer that had been formed within the PhK
      holoenzyme by formaldehyde, a nearly zero-length cross-linker. Because the region
      of gamma that we found to interact with alpha has previously been shown to
      contain a high affinity binding site for calmodulin (Dasgupta, M., Honeycutt, T.,
      and Blumenthal, D. K. (1989) J. Biol. Chem. 264, 17156-17163), we tested the
      influence of Ca(2+) on the conformation of the alpha subunit and found that the
      region of alpha that interacts with gamma was, in fact, perturbed by Ca(2+). The
      results herein support the existence of a Ca(2+)-sensitive communication network
      among the delta, gamma, and alpha subunits, with the regulatory domain of gamma
      being the primary mediator. The similarity of such a Ca(2+)-dependent network to
      the interactions among troponin C, troponin I, and actin is discussed in light of
      the known structural and functional similarities between troponin I and the gamma
      subunit of PhK.

PMID- 11847236
TI  - Submergence research using Rumex palustris as a model; looking back and going
      forward.
AB  - Flooding is a phenomenon that destroys many crops worldwide. During evolution
      several plant species evolved specialized mechanisms to survive short- or long
      term waterlogging and even complete submergence. One of the plant species that
      evolved such a mechanism is Rumex palustris. When flooded, this plant species is
      capable to elongate its petioles to reach the surface of the water. Thereby it
      restores normal gas exchange which leads to a better survival rate. Enhanced
      levels of ethylene, due to physical entrapment, is the key signal for the plant
      that its environment has changed from air to water. Subsequently, a signal
      transduction cascade involving at least four (classical) plant hormones,
      ethylene, auxin, abscisic acid, and gibberellic acid, is activated. This results
      in hyponastic growth of the leaves accompanied by a strongly enhanced elongation
      rate of the petioles enabling them to reach the surface. Other factors, among
      them cell wall loosening enzymes have been shown to play a role as well.

PMID- 11847237
TI  - Comparison of mRNA levels of three ethylene receptors in senescing flowers of
      carnation (Dianthus caryophyllus L.).
AB  - Three ethylene receptor genes, DC-ERS1, DC-ERS2 and DC-ETR1, were previously
      identified in carnation (Dianthus caryophyllus L.). Here, the presence of mRNAs
      for respective genes in flower tissues and their changes during flower senescence
      are investigated by Northern blot analysis. DC-ERS2 and DC-ETR1 mRNAs were
      present in considerable amounts in petals, ovaries and styles of the flower at
      the full-opening stage. In the petals the level of DC-ERS2 mRNA showed a
      decreasing trend toward the late stage of flower senescence, whereas it increased
      slightly in ovaries and was unchanged in styles throughout the senescence period.
      However, DC-ETR1 mRNA showed no or little changes in any of the tissues during
      senescence. Exogenously applied ethylene did not affect the levels of DC-ERS2 and
      DC-ETR1 mRNAs in petals. Ethylene production in the flowers was blocked by
      treatment with 1,1-dimethyl-4-(phenylsulphonyl)semicarbazide (DPSS), but the mRNA
      levels for DC-ERS2 and DC-ETR1 decreased in the petals. DC-ERS1 mRNA was not
      detected in any cases. These results indicate that DC-ERS2 and DC-ETR1 are
      ethylene receptor genes responsible for ethylene perception and that their
      expression is regulated in a tissue-specific manner and independently of ethylene
      in carnation flowers during senescence.

PMID- 11847238
TI  - Is a cysteine proteinase inhibitor involved in the regulation of petal wilting in
      senescing carnation (Dianthus caryophyllus L.) flowers?
AB  - Senescence of carnation petals is accompanied by autocatalytic ethylene
      production and wilting of the petals; the former is caused by the expression of 1
      aminocyclopropane-1-carboxylate (ACC) synthase and ACC oxidase genes and the
      latter is related to the expression of a cysteine proteinase (CPase) gene. CPase
      is probably responsible for the degradation of proteins, leading to the
      decomposition of cell components and resultant cell death during the senescence
      of petals. The carnation plant also has a gene for the CPase inhibitor (DC-CPIn)
      that is expressed abundantly in petals at the full opening stage of flowers. In
      the present study, DC-CPIn cDNA was cloned and expressed in E. coli. The
      recombinant DC-CPIn protein completely inhibited the activities of a proteinase
      (CPase) extracted from carnation petals and papain. Northern blot analysis showed
      that the mRNA for CPase (DC-CP1) accumulated in large amounts, whereas that for
      DC-CPIn disappeared, corresponding to the onset of petal wilting in flowers
      undergoing natural senescence and exogenous ethylene-induced senescence. Based on
      these findings, a role of DC-CPIn in the regulation of petal wilting is
      suggested; DC-CPIn acts as a suppressor of petal wilting, which probably
      functions to fine-tune petal wilting in contrast to coarse tuning, the up
      regulation of CPase activity by gene expression.

PMID- 11847239
TI  - Detection of ethylene receptor protein Cm-ERS1 during fruit development in melon
      (Cucumis melo L.).
AB  - Antibodies against melon ethylene receptor, Cm- ERS1 was prepared. Cm-ERS1
      protein formed a disulphide-linked homodimer and it was present in microsomal
      membranes but not in soluble fractions. Cm-ERS1 protein was present at high
      levels in melon fruit during early developmental stages. This transition pattern
      was also observed in another melon cultivar.

PMID- 11847240
TI  - Short-term metabolic responses of soybean root nodules to nitrate.
AB  - Soybean (Glycine max L. Merr.) plants exposed to 10 mM KNO(3) for a 4 d period
      were used to test the correlation between nitrogenase activity, gene expression
      and sucrose metabolism. Nitrate caused the down-regulation of sucrose synthase
      (SS) transcripts within 1 d, although a decline in nodule SS activity and an
      increase in nodule sucrose content only occurred after 3-4 d. In a second
      experiment, plants were exposed to (15)N-labelled nitrate for 48 h to determine
      the time period during which nitrate was taken up, and to relate this to the
      decline in apparent nitrogenase activity (H(2) production in air) and the
      reduction in SS gene transcript levels. The peak of nitrate uptake appeared to be
      between 8 h and 14 h whilst apparent nitrogenase activity began to decline at
      about 17.5 h. The SS mRNA signal declined markedly between 14 h and 24 h. The
      correlative association of these factors is clear. However, SS activity per se
      does not appear to be related to the initial decline in apparent nitrogenase
      activity as a result of nitrate uptake. These findings, therefore, do not support
      the hypothesis that the regulation of nodule function is mediated by the
      regulation of SS activity.

PMID- 11847241
TI  - Ethylene-responsive genes are differentially regulated during abscission, organ
      senescence and wounding in peach (Prunus persica).
AB  - Ethylene-responsive genes from peach (Prunus persica, L. Batsch) were isolated by
      differential screening of a cDNA library constructed from abscission zones in
      which cell separation had been evoked by treatment with the ethylene analogue
      propylene. DNA and deduced protein sequences of four selected clones, termed
      Prunus persica Abscission zone (PpAz), revealed homology to thaumatin-like
      proteins (PpAz8 and PpAz44), to proteins belonging to the PR4 class of
      pathogenesis-related (PR) proteins (PpAz89), and to fungal and plant beta-D
      xylosidases (PpAz152). Expression analyses conducted on embrioctomized and CEPA
      treated fruitlets as well as on fruit explants have shown that PpAz8, PpAz44 and
      PpAz89 are preferentially transcribed in the cells of the fruit abscission zone
      rather than in the non-zone tissues. The PpAz152 transcript showed a different
      accumulation pattern being consistently and promptly induced by wounding and only
      slightly stimulated by propylene. By contrast, a complex pattern of transcript
      accumulation was found for the four genes in response to the wounding of leaves
      and during organ development and senescence. Based on this evidence, the
      existence of multiple regulatory pathways underlying the differential expression
      of the four PpAz genes in the different tissues and physiological processes is
      hypothesized.

PMID- 11847242
TI  - Modulation of cyanoalanine synthase and O-acetylserine (thiol) lyases A and B
      activity by beta-substituted alanyl and anion inhibitors.
AB  - The reaction mechanisms of three enzymes belonging to a single gene family are
      compared: a cyanoalanine synthase and two isoforms of O-acetylserine (thiol)
      lyase (O-ASTL) isolated from spinach (Spinacea oleracea L. cv. Medina). O-ASTL
      represents a major regulatory point in the S-assimilatory pathway, and the
      related cyanoalanine synthase, which is specific to the mitochondrial
      compartment, has evolved an independent function of cyanide detoxification. All
      three enzymes catalysed both the cysteine synthesis and cyanoalanine synthesis
      reactions although with different efficiencies, and which may be explained by a
      single amino acid substitution in the substrate-binding pocket of the enzyme.
      Substituted alanine and nucleophillic inhibitors caused predominantly non
      competitive inhibition, indicating binding to both E- and F-forms of the enzyme
      in a bi-bi ping-pong kinetic model. Michaelis-Menten kinetics were observed when
      the alanyl substrate was varied in the presence and absence of inhibitors. The
      use of alanyl inhibitors has shown that the alanyl half-cycle of both the
      cysteine synthesis and cyanoalanine synthesis reactions of cyanoalanine synthase
      and O-acetylserine (thiol) lyases are similar. This is in contrast to the results
      observed with nucleophillic inhibitors, which have shown that the mechanisms of
      anion binding and processing differ between cyanoalanine synthase and O-ASTLs.

PMID- 11847243
TI  - Influence of prior Cd(2+) exposure on the uptake of Cd(2+) and other elements in
      the phytochelatin-deficient mutant, cad1-3, of Arabidopsis thaliana.
AB  - In order to test the potential effect of prior exposure to different Cd
      concentrations on Cd uptake and accumulation, plants of Arabidopsis thaliana,
      including a phytochelatin-deficient mutant, cad1-3, and the wild type, were
      compared. For Cd uptake experiments, plants were grown for 1 week in nutrient
      solution containing different Cd concentrations (0, 0.05, 0.1, 0.25, 0.5, and 1.0
      microM Cd(NO(3))(2)). Thereafter they were subjected to 0.5 microM Cd labelled
      with (109)Cd for 2 h. Uptake experiments with (109)Cd showed that the
      phytochelatin-deficient mutant cad1-3, accumulated less Cd than the wild type.
      Both a lower proportion and lower total amount of absorbed Cd were translocated
      to the shoot in cad1-3 plants compared to wild-type plants. Cadmium exposure also
      influenced the amounts of nutrients found, whereby after exposure to high Cd
      concentrations (0.5, 1.0 microM) during growth, cad1-3 roots contained less Fe,
      K, Mg, P, and S compared to roots of the wild type. In cad1-3 these elements
      decreased with increasing Cd concentration. The total Cd content in roots and
      shoots increased significantly with increasing Cd concentration during growth,
      although the increase was much less in cad1-3 plants. In time-dependent
      experiments of Cd uptake carried out between 15 and 120 min on plants not
      previously exposed to Cd, no significant difference in Cd accumulation between
      the mutant and wild type were found, although a smaller amount of Cd was
      translocated to the shoot in cad1-3 plants. The possibility that the differences
      in Cd accumulation in mutant and wild-type lines may be due to the cytosolic Cd
      regulation, which is inhibited by the complexation of Cd by phytochelatins, is
      discussed.

PMID- 11847244
TI  - Lipid metabolism in the moss Rhytidiadelphus squarrosus (Hedw.) Warnst. from lead
      contaminated and non-contaminated populations.
AB  - Lipid metabolism and the effect of Pb(2+) and Cu(2+) on this process was studied
      in the moss Rhytidiadelphus squarrosus collected from both a lead-contaminated
      and a non-contaminated site. Total radiolabelling of lipids from [1-(14)C]acetate
      was similar in both populations and Cu or Pb (1 microM, 10 microM) did not cause
      much alteration in acute exposure experiments. However, there were significant
      qualitative changes. Of the major labelled neutral lipid classes, samples from
      the lead-polluted site showed a decrease in labelling of triacylglycerols and an
      increase in wax esters. Acute lead exposure caused similar effects. Cu caused a
      decrease in the labelling of wax esters and an increase in diacylglycerols. These
      data suggest that heavy metals cause a change in carbon flux through the
      acylation reactions associated with the Kennedy pathway. R. squarrosus obtained
      from the Pb-contaminated site also showed changes in polar lipid labelling
      compared to the uncontaminated site. The labelling of phosphatidylcholine was
      more than halved and replaced by increased labelling of other zwitterionic
      lipids. The chloroplast glycerolipids were also increasingly labelled. Acute
      exposure to Pb, however, caused little alteration of labelling patterns within 24
      h. R. squarrosus contains high levels of polyunsaturated fatty acids (PUFAs), but
      moss obtained from the Pb-polluted site had significantly less PUFAs containing
      three or more double bonds. Such samples, when incubated with [1-(14)C]acetate
      also showed decreased PUFA labelling. By contrast, acute exposure to Pb produced
      different results. These data provide a foundation for examining lipid metabolism
      in bryophytes and the effects of pollution in this important class of organism.
      The results also emphasize that acute and chronic exposure to heavy metals may
      produce different effects and that caution must be exercised in extrapolating
      data from one system to another.

PMID- 11847245
TI  - In situ hybridization of the MADS-box gene POTM1 during potato floral
      development.
AB  - The potato MADS-box gene POTM1 is a member of the SQUA-like family of plant MADS
      box genes. The amino acid sequence of POTM1 most closely matches the sequence of
      PFG (Petunia Flowering Gene), a petunia MADS-box gene involved in the transition
      from vegetative to reproductive development. To examine the likely role of POTM1
      in potato reproductive tissue, in situ hybridizations were performed on sections
      of the potato shoot apex at various stages during the transition to flowering.
      Scanning electron micrographs provide a reference for each stage to illustrate
      the progression from vegetative meristem to inflorescence meristem and floral
      organs. POTM1 mRNA accumulates in vegetative, inflorescence and floral meristems.
      Transcripts are present in petal primordia during the later stages of petal
      development and they accumulate later during floral development inside the
      stamens and carpels, but not in carpel walls. This widespread pattern of mRNA
      accumulation is unique among the SQUA-like genes and indicates that POTM1 is
      active during a variety of stages of development, and may function in regulating
      cell determination in transitional phases of both vegetative and floral
      meristems.

PMID- 11847246
TI  - Leaf initiation and development in soybean under phosphorus stress.
AB  - Experiments investigated changes in leaf development in young soybean plants
      progressing into P stress. The apical meristem and leaf structure were examined
      anatomically to evaluate the involvement of cell division and cell expansion in
      the restriction of leaf number and individual leaf size. Seedlings were deprived
      of P for 32 d following germination. Leaf initiation rates declined noticeably
      after about 2 weeks, even though the apical dome was of similar size and had a
      similar number of cells as controls. Primordia appeared morphologically similar
      also. Expansion of primary and the first three trifoliolate leaves of -P plants
      was severely reduced, and expansion of each leaf ceased, uniformly, when an area
      of about 40 cm(2) was obtained. Leaf epidermal cell size in the lateral plane was
      unaffected. The results indicate that expansion of leaves under P stress was
      limited by the number of cell divisions, which would imply control of cell
      division by a common regulatory factor within the leaf canopy.

PMID- 11847247
TI  - Fusiform cells in the cambium of Kalopanax pictus are exclusively mononucleate.
AB  - While it is generally accepted that most plant cells are mononucleate, it has
      been argued with some vehemence that fusiform cambial cells can be multinucleate.
      The controversy has not been resolved since to date, studies by conventional
      microscopy and transmission electron microscopy have failed to confirm
      unambiguously whether cambial cells are mononucleate or multinucleate. In this
      study, semi-thin sections of epoxy-embedded specimens and thick slices of cambial
      tissues from the hardwood Kalopanax pictus were analysed by confocal laser
      scanning microscopy. Tangential sections of cambium, regardless of the thickness
      of the section, are likely to contain portions of cells in several adjacent
      layers of cells and, at the lower resolution of conventional microscopy, several
      adjacent cells can appear to be a single cell with more than one nucleus. The
      higher resolution in the third dimension of confocal microscopy allowed clearly
      adjacent layers of cells in the cambium to be distinguished and the number of
      nuclei per cell to be determined. In this tree, the cambial cells were
      mononucleate in all cases.

PMID- 11847248
TI  - Growth-induced water potentials and the growth of maize leaves.
AB  - Profiles of water potential (Psi(w)) were measured from the soil through the
      plant to the tip of growing leaves of fully established maize (Zea mays L.). The
      profiles revealed gradients in transpiration-induced Psi(w) extending upward
      along the transpiration path, and growth-induced Psi(w) extending radially
      between the veins in the elongating region of the leaf base. Water moving upward
      required a small gradient while that moving radially required a much larger
      gradient primarily because the protoxylem vessels were encased in many small,
      undifferentiated cells that were likely to act as a barrier to radial flow. Upon
      maturation, these small cells enlarged and some began to conduct water, probably
      decreasing the barrier. In the mature leaf, the growth-induced Psi(w) were absent
      but the transpiration-induced Psi(w) remained. When leaves were growing, the
      growth-induced Psi(w) moved water into the elongating cells during the day and
      night, and it shifted with changes in transpiration-induced Psi(w). The shift
      involved solutes accumulating in the growing region. When water was withheld, the
      growth-induced Psi(w) disappeared and leaf elongation ceased even though turgor
      pressure was at its highest. Turgor was maintained by osmotic adjustment that
      doubled the osmotic potential of the elongating cells. If elongation resumed at
      night or with rewatering, the growth-induced Psi(w) reappeared. If pressure was
      applied to the soil/root system to cause guttation and re-establish the growth
      induced Psi(w), elongation resumed immediately. These findings support the
      hypothesis that the primary control of growth is the disappearance and
      reappearance of the growth-induced Psi(w) because the potential changed in the
      xylem and nearby cells, blocking or permitting radial water movement and thus
      blocking or permitting growth.

PMID- 11847249
TI  - Induction of early bolting in Arabidopsis thaliana by triacontanol, cerium and
      lanthanum is correlated with increased endogenous concentration of isopentenyl
      adenosine (iPAdos).
AB  - The effects of triacontanol (TRIA), applied singly or in combination with cerium
      nitrate and lanthanum nitrate, on bolting of Arabidopsis thaliana were studied.
      Triacontanol (0.1 to 0.6 microM) added to the culture medium induced early
      bolting. TRIA (0.3 microM) applied with low concentrations of cerium and
      lanthanum caused a synergistic stimulation of bolting. In medium containing 0.3
      microM TRIA, 0.1 microM cerium nitrate and 0.1 mM lanthanum nitrate, 82% of the
      plants bolted 20 d after seed sowing compared to only 8.6% in basal medium and
      47.8% in medium with TRIA only. The changes in the endogenous concentrations of
      total cytokinins of the isopentenyl adenine (IP) subfamily in the leaf and root
      tissues were correlated with TRIA-induced early bolting. The combined treatment
      of TRIA (0.3 microM), cerium nitrate (0.1 microM) and lanthanum nitrate (0.1 mM)
      resulted in a significant increase in the endogenous concentrations of total
      cytokinins of the IP subfamily in the root and leaf tissues compared to plants
      growing in the basal medium and medium with TRIA. The exogenous application of
      six natural cytokinins to the plants revealed that only isopentenyl adenosine
      (iPAdos) was as effective as TRIA on floral bud formation. iPAdos was also found
      to have similar effects as TRIA on root growth and reproductive growth. These
      results suggest a correlation between the early bolting induced by TRIA, cerium
      and lanthanum and the production of higher concentrations of endogenous iPAdos.

PMID- 11847250
TI  - Organization of cell walls in Sandersonia aurantiaca floral tissue.
AB  - Visual symptoms of the onset of senescence in Sandersonia aurantiaca flowers
      begin with fading of flower colour and wilting of the tissue. When fully
      senescent, the flowers form a papery shell that remains attached to the plant.
      The cell walls of these flowers have been examined to determine whether there are
      wall modifications associated with the late stages of expansion and subsequent
      senescence-related wilting. Changes in the average molecular size of pectin were
      limited through flower opening and senescence, although there was a loss of
      neutral sugar-containing side-branches from pectins in opening flowers, and the
      total amounts of pectin and cellulose continued to rise in cell walls of fully
      senescent sandersonia flowers. Xyloglucan endotransglycosylase activity increased
      in opening and mature flowers, but declined sharply as flowers wilted.
      Concomitantly, the proportion of hemicellulose polymers of increasing molecular
      weight increased from flower expansion up to the point at which wilting occurred.
      Approximately 50% of the non-cellulosic neutral sugar in mature flower cell walls
      was galactose, primarily located in an insoluble cell wall fraction. Total
      galactose in this fraction increased per flower with maturity, then declined at
      the onset of wilting. Beta-galactosidase activity was low in expanding tepals,
      but increased as flowers matured and wilted.

PMID- 11847251
TI  - Localized versus systemic effect of arbuscular mycorrhizal fungi on defence
      responses to Phytophthora infection in tomato plants.
AB  - Development of biological control for plant diseases is accepted as a durable and
      environmentally friendly alternative for agrochemicals. Arbuscular mycorrhizal
      fungi (AMF), which form symbiotic associations with root systems of most
      agricultural, horticultural and hardwood crop species, have been suggested as
      widespread potential bioprotective agents. In the present study the ability of
      two AMF (Glomus mosseae and Glomus intraradices) to induce local or systemic
      resistance to Phytophthora parasitica in tomato roots have been compared using a
      split root experimental system. Glomus mosseae was effective in reducing disease
      symptoms produced by P. parasitica infection, and evidence points to a
      combination of local and systemic mechanisms being responsible for this
      bioprotector effect. The biochemical analysis of different plant defence-related
      enzymes showed a local induction of mycorrhiza-related new isoforms of the
      hydrolytic enzymes chitinase, chitosanase and beta-1,3-glucanase, as well as
      superoxide dismutase, an enzyme which is involved in cell protection against
      oxidative stress. Systemic alterations of the activity of some of the
      constitutive isoforms were also observed in non-mycorrhizal roots of mycorrhizal
      plants. Studies on the lytic activity against Phytophthora cell wall of root
      protein extracts also corroborated a systemic effect of mycorrhizal symbiosis on
      tomato resistance to Phytophthora.

PMID- 11847252
TI  - Characteristics of cadmium uptake in two contrasting ecotypes of the
      hyperaccumulator Thlaspi caerulescens.
AB  - Uptake of Cd and Zn by intact seedlings of two contrasting ecotypes of the
      hyperaccumulator Thlaspi caerulescens was characterized using radioactive
      tracers. Uptake of Cd and Zn at 2 degrees C was assumed to represent mainly
      apoplastic binding in the roots, whereas the difference in uptake between 22
      degrees C and 2 degrees C represented metabolically dependent influx. There was
      no significant difference between the two ecotypes in the apoplastic binding of
      Cd or Zn. Metabolically dependent uptake of Cd was 4.5-fold higher in the high Cd
      accumulating ecotype, Ganges, than in the low Cd-accumulating ecotype, Prayon. By
      contrast, there was only a 1.5-fold difference in the Zn uptake between the two
      ecotypes. For the Ganges ecotype, Cd uptake could be described by Michaelis
      Menten kinetics with a V(max) of 143 nmol g(-1) root FW h(-1) and a K(m) of 0.45
      microM. Uptake of Cd by the Ganges ecotype was not inhibited by La, Zn, Cu, Co,
      Mn, Ni or Fe(II), and neither by increasing the Ca concentration. By contrast,
      addition of La, Zn or Mn, or increasing the Ca concentration in the uptake
      solution decreased Cd uptake by Prayon. Uptake of Ca was larger in Prayon than in
      Ganges. The results suggest that Cd uptake by the low Cd-accumulating ecotype
      (Prayon) may be mediated partly via Ca channels or transporters for Zn and Mn. By
      contrast, there may exist a highly selective Cd transport system in the root cell
      membranes of the high Cd-accumulating ecotype (Ganges) of T. caerulescens.

PMID- 11847253
TI  - The CO(2) response of Vicia guard cells acclimates to growth environment.
AB  - Stomata of growth chamber-grown Vicia faba leaves have an enhanced CO(2)
      response, measured as change in stomatal aperture, compared to stomata of
      greenhouse-grown leaves. Reciprocal transfer experiments showed that the stomatal
      response to CO(2) acclimated to the growing environment. Stomata of growth
      chamber-grown leaves transferred to a greenhouse lost their high CO(2)
      sensitivity within 2-3 d while stomata of greenhouse-grown leaves transferred to
      a growth chamber acquired a high CO(2) sensitivity within 5-7 d. Experiments
      measuring the CO(2) responses of stomata in detached epidermis showed that growth
      chamber and greenhouse-grown stomata have the same contrasting CO(2) sensitivity
      observed in the intact leaf, indicating that the responses reflect intrinsic
      guard cell properties. The acclimation properties of the CO(2) response of guard
      cells have implications for the understanding of stomatal function under the
      predicted increases in atmospheric CO(2).

PMID- 11847254
TI  - Drying rate and dehydrin synthesis associated with abscisic acid-induced
      dehydration tolerance in Spathoglottis plicata orchidaceae protocorms.
AB  - Dehydration tolerance of in vitro orchid protocorms was investigated under
      controlled drying conditions and after abscisic acid (ABA) pretreatment.
      Protocorms were obtained by germinating seeds on Murashige and Skoog (MS) medium
      containing 10% (v/v) coconut water, 2% (w/v) sucrose and 0.8% (w/v) agar, and
      were dehydrated in relative humidities (RH) ranging from 7% to 93% at 25 degrees
      C. The critical water content of dehydration tolerance was determined, using the
      electrolyte leakage method. Drying rate affected the critical water content. Slow
      drying under high RH conditions achieved the greatest tolerance to dehydration.
      ABA pretreatment decreased the drying rate of protocorms, and increased
      dehydration tolerance. Improved tolerance to dehydration after ABA treatment was
      correlated with the effect of ABA on drying rate of protocorms. When critical
      water content of protocorms dried under different RH was plotted as a function of
      actual drying rate, no significant difference in tolerance to dehydration was
      observed between ABA-treated and control protocorms. ABA pretreatment and
      dehydration of orchid protocorms induced the synthesis of dehydrin, especially
      under the slow drying conditions. ABA pretreatment also promoted dry matter
      accumulation such as carbohydrates and soluble proteins and increased the
      concentration of K(+) and Na(+) ions in protocorms. The ABA-induced decrease in
      drying rate was correlated with lower osmotic potential, the enhanced maturity of
      protocorms and the accumulation of dehydrin in protocorms during pretreatment.

PMID- 11847255
TI  - A new method to determine the oxygen concentration inside the sapwood of trees.
AB  - Research into the short-term fluctuations of oxygen concentrations in tree stems
      has been hampered by the difficulty of measuring oxygen inside tissues. A new
      method, which is based on fluorescence quenching of a ruthenium complex in the
      presence of oxygen, has been applied to measure changes of oxygen concentration
      in the sapwood of trees. During a field day-course oxygen increased with the
      radiation load and fell during the night (in Fagus orientalis from 20.3% in the
      afternoon to 17.5% in the morning next day). In a greenhouse experiment the
      sapwood oxygen concentration of Laurus nobilis could be influenced by flooding
      the root system. The very fast response, high resolution (better than 0.1%), easy
      calibration, and dependence only on oxygen and temperature make the technique
      well suited for measurements of oxygen concentrations in the sapwood.

PMID- 11847256
TI  - PARF-1: an Arabidopsis thaliana FYVE-domain protein displaying a novel eukaryotic
      domain structure and phosphoinositide affinity.
AB  - A full-length cDNA encoding a novel protein named PARF-1 was isolated from
      Arabidopsis thaliana. PARF-1 is the first eukaryotic protein to be identified
      that displays a domain structure which includes a FYVE-finger domain, a
      Pleckstrin Homology (PH) domain, as well as multiple Regulator of Chromosome
      Condensation-1 (RCC1) repeats. Northern blot analysis revealed that PARF-1 mRNA
      is present at high levels in flowers, but only at very low levels in other
      tissues. Recombinant PARF-1 fusion proteins expressed in E. coli were found to
      display unique binding specificities for monophosphorylated phosphoinositide
      lipids. The unusual domain structure of PARF-1 combined with its phosphoinositide
      specificity suggests that it may fulfil unexpected functions in higher plants.

PMID- 11847257
TI  - Motion of the calcaneus, navicular, and first metatarsal during the stance phase
      of walking.
AB  - One hundred fifty-three subjects between the ages of 18 and 41 years (mean age,
      26.2 years) with no history of congenital or traumatic deformity or foot problems
      walked along a 6-m walkway while the angular and linear displacement of the
      tibia, calcaneus, navicular, and first metatarsal was measured by means of an
      electromagnetic motion analysis system. Three-dimensional movement of the
      calcaneus relative to the tibia, of the navicular relative to the calcaneus, and
      of the first metatarsal relative to the navicular during the stance phase of gait
      was calculated. The results of this study provide information on, and an
      understanding of, how the calcaneus, navicular, and first metatarsal function
      during the stance phase of normal human walking.

PMID- 11847258
TI  - Kinematics of the midtarsal joint during standing leg rotation.
AB  - Building on previous work that was cadaver based or involved invasive techniques,
      this study quantifies the kinematics of an approximation of the midtarsal joint
      with a noninvasive method. Three-dimensional kinematic data describing the motion
      of the forefoot and heel during transverse plane rotation of the leg were
      collected from 25 subjects by means of reflective markers and four infrared
      cameras. The motion between these segments was assumed to be the best possible
      clinical approximation of the midtarsal joint. The kinematic characteristics of
      the midtarsal joint were described in terms of the range and direction of motion
      in each cardinal body plane, the ratio of the range of motion in each plane, and
      the orientation of the axis of rotation. The characteristics of the midtarsal
      joint changed during the range of motion; thus, multiple axes of rotation could
      be calculated and joint characteristics were varied among subjects. The results
      of this in vivo method were generally consistent with those of cadaver studies
      and invasive in vivo studies.

PMID- 11847259
TI  - Stability of the offset V-osteotomy. Test jig development and saw bone model
      assessment.
AB  - In the offset V-bunionectomy used for hallux valgus repair, both the Kalish and
      the Vogler variations have a long dorsal arm, but the apex is more distal in the
      Kalish procedure. This study investigated the effect that pin orientation and
      location of the osteotomy apex have on weightbearing stability. The authors
      studied saw bone models that were loaded to failure in an Instron 4201 materials
      testing machine and, in addition, designed, fabricated, and used a unique jig
      assembly to help minimize data variability. Statistically significant differences
      were found between the surgical techniques and pin orientations: the Kalish
      osteotomy was stronger than the Vogler procedure, and in both osteotomies, the
      plantarly directed Kirschner wire orientation was stronger than the dorsally
      directed orientation.

PMID- 11847260
TI  - Limb salvage in recurrent synovial sarcoma of the right ankle and lower leg.
AB  - Synovial sarcoma of the extremities represents 7% of all soft-tissue sarcomas.
      This article presents the case of a patient who was treated for a synovial
      sarcoma of the lateral aspect of the distal lower leg extending to the ankle and
      involving the fibular bone. The patient underwent a wide excision of the tumor,
      including the fibular bone, followed by radiation and chemotherapy, rather than
      undergo an amputation of the right leg. Consideration is also given to the
      traumatic etiology of the tumor.

PMID- 11847261
TI  - Variations in the origin of the medial calcaneal nerve.
AB  - Previous anatomic studies of the medial heel region were done on embalmed human
      cadavers. Here, the innervation of the medial heel region was studied by
      dissecting living tissue with the use of 3.5-power loupe magnification during
      decompression of the medial ankle for tarsal tunnel syndrome in 85 feet. The
      medial heel was found to be innervated by just one medial calcaneal nerve in 37%
      of the feet, by two medial calcaneal nerves in 41%, by three medial calcaneal
      nerves in 19%, and by four medial calcaneal nerves in 3%. An origin for a medial
      calcaneal nerve from the medial plantar nerve was found in 46% of the feet. This
      nerve most often innervates the skin of the posteromedial arch, where it is at
      risk for injury during calcaneal spur removal or plantar fasciotomy. Knowledge of
      the variations in location of the medial calcaneal nerves may prevent neuroma
      formation during surgery and provide insight into the variability of heel
      symptoms associated with tarsal tunnel syndrome.

PMID- 11847262
TI  - A retrospective analysis of 772 patients with hallux limitus.
AB  - In this retrospective analysis of 772 patients with symptomatic hallux limitus,
      428 patients (55%) were successfully treated with conservative care alone; of
      these 428 patients, 362 (84%) were treated with orthoses. Corticosteroid
      injections and a change in shoes allowed 24 patients (6% of conservatively
      treated patients) and 42 patients (10%), respectively, to have less discomfort
      and return to previous activity levels. Overall, 47% of the patients in this
      analysis were successfully treated with orthoses. Surgical procedures were
      performed on 296 patients (38% of all patients) who did not respond to
      conservative care. In this analysis, 48 of the patients (6% of all patients) who
      did not respond to conservative care either refused surgery or were not surgical
      candidates. These data are intended to provide podiatric physicians with expected
      outcomes for conservative care of hallux limitus. The etiology, symptoms,
      conservative management, and surgical treatments of hallux limitus and hallux
      rigidus are also reviewed.

PMID- 11847264
TI  - Infant heel nodules. Calcification of epidermal cysts.
AB  - Calcified nodules of the heel have been reported in high-risk neonates following
      multiple needle sticks to draw blood. Previous reports suggest that the needle
      stick trauma causes dystrophic calcification. A case of multiple discrete firm
      heel lesions, which began shortly after birth in an immature-birth weight neonate
      who had sustained multiple needle sticks of the heel, is presented.
      Histologically, these lesions demonstrated foci of calcification and fragments of
      keratin surrounded by an epithelial lining, suggesting that calcified nodules may
      also arise from epidermal implantation cysts that secondarily calcify.

PMID- 11847263
TI  - Clonic focal seizure of the foot secondary to nonketotic hyperglycemia.
AB  - Focal epileptic seizures can be the first manifestation of a diabetic disorder.
      Metabolic disturbances, including hyperglycemia, mild hyperosmolality,
      hyponatremia, and lack of ketoacidosis contribute to the development of partial
      focal seizures. A review of the medical literature for partial focal seizures is
      presented, followed by a case study of a patient who developed clonic seizures of
      the right foot secondary to hyperglycemia, hyponatremia, and hyperosmolality.

PMID- 11847266
TI  - Integrating research into the clinic. What evidence based practice means to the
      practising podiatrist.
AB  - This paper is the first in a series of three aimed at introducing clinicians to
      current concepts in research, and outlining how they may be able to apply these
      concepts to their own clinical practice. It has become evident in recent years
      that while many practitioners may not want to become actively involved in the
      research process, simply keeping abreast of the burgeoning publication base will
      create new demands on their time, and will often require the acquisition of new
      skills. This series introduces the philosophies of integrating what sometimes may
      appear to be abstract research into the realities of the clinical environment. It
      will provide practitioners with an accessible summary of the tools required in
      order to understand the research process. For some, it is hoped this series may
      provide some impetus for the contemplative practitioner to become a more active
      participant in the research process. This first paper addresses how the evidence
      based practice (EBP) revolution can be used to empower the individual
      practitioner and how good quality evidence can improve the overall clinical
      decision making process. It also suggests key strategies by which the clinician
      may try to enhance their clinical decision making process and make research
      evidence more applicable to their day to day clinical practice.

PMID- 11847268
TI  - Detecting equilibrium cytochrome c folding intermediates by electrospray
      ionisation mass spectrometry: two partially folded forms populate the molten
      globule state.
AB  - Nanoelectrospray ionization mass spectrometry (nano-ESI-MS) is applied to the
      characterization of ferric cytochromec (cytc) conformational states under
      different solvent conditions. The methanol-induced molten-globule state in the pH
      range 2.6-3.0 is found to be populated by two distinct, partially folded
      conformers I(A) and I(B). The more compact intermediate I(B) resembles that
      induced by glycerol in acid-unfolded cytc. The less compact one, I(A), also can
      be induced by destabilization of the native structure by trifluoroethanol. I(A)
      and I(B) can be detected, in the absence of additives, around the midpoint of the
      acid-induced unfolding transition, providing direct evidence for involvement of
      equilibrium folding intermediates in cytc conformational transitions at low pH.
      This study shows that mass spectrometry can contribute to the characterization of
      molten-globule states of proteins by detection of distinct, although poorly
      populated, conformations involved in a dynamic equilibrium.

PMID- 11847269
TI  - Alternative type I and I' turn conformations in the beta8/beta9 beta-hairpin of
      human acidic fibroblast growth factor.
AB  - Human acidic fibroblast growth factor (FGF-1) has a beta-trefoil structure, one
      of the fundamental protein superfolds. The X-ray crystal structures of wild-type
      and various mutant forms of FGF-1 have been solved in five different space
      groups: C2, C222(1), P2(1) (four molecules/asu), P2(1) (three molecules/asu), and
      P2(1)2(1)2(1). These structures reveal two characteristically different
      conformations for the beta8/beta9 beta-hairpin comprising residue positions 90
      94. This region in the wild-type FGF-1 structure (P2(1), four molecules/asu), a
      his-tagged His93-->Gly mutant (P2(1), three molecules/asu) and a his-tagged
      Asn106-->Gly mutant (P2(1)2(1)2(1)) adopts a 3:5 beta-hairpin known as a type I
      (1-4) G1 beta-bulge (containing a type I turn). However, a his-tagged form of
      wild-type FGF-1 (C222(1)) and a his-tagged Leu44-->Phe mutant (C2) adopt a 3:3
      beta-hairpin (containing a type I' turn) for this same region. A feature that
      distinguishes these two types of beta-hairpin structures is the number and
      location of side chain positions with eclipsed C(beta) and main-chain carbonyl
      oxygen groups (Psi is equivalent to +60 degrees). The effects of glycine
      mutations upon stability, at positions within the hairpin, have been used to
      identify the most likely structure in solution. Type I' turns in the structural
      data bank are quite rare, and a survey of these turns reveals that a large
      percentage exhibit crystal contacts within 3.0 A. This suggests that many of the
      type I' turns in X-ray structures may be adopted due to crystal packing effects.

PMID- 11847270
TI  - EstB from Burkholderia gladioli: a novel esterase with a beta-lactamase fold
      reveals steric factors to discriminate between esterolytic and beta-lactam
      cleaving activity.
AB  - Esterases form a diverse class of enzymes of largely unknown physiological role.
      Because many drugs and pesticides carry ester functions, the hydrolysis of such
      compounds forms at least one potential biological function. Carboxylesterases
      catalyze the hydrolysis of short chain aliphatic and aromatic carboxylic ester
      compounds. Esterases, D-alanyl-D-alanine-peptidases (DD-peptidases) and beta
      lactamases can be grouped into two distinct classes of hydrolases with different
      folds and topologically unrelated catalytic residues, the one class comprising of
      esterases, the other one of beta-lactamases and DD-peptidases. The chemical
      reactivities of esters and beta-lactams towards hydrolysis are quite similar,
      which raises the question of which factors prevent esterases from displaying beta
      lactamase activity and vice versa. Here we describe the crystal structure of
      EstB, an esterase isolated from Burkholderia gladioli. It shows the protein to
      belong to a novel class of esterases with homology to Penicillin binding
      proteins, notably DD-peptidase and class C beta-lactamases. Site-directed
      mutagenesis and the crystal structure of the complex with diisopropyl
      fluorophosphate suggest Ser75 within the "beta-lactamase" Ser-x-x-Lys motif to
      act as catalytic nucleophile. Despite its structural homology to beta-lactamases,
      EstB shows no beta-lactamase activity. Although the nature and arrangement of
      active-site residues is very similar between EstB and homologous beta-lactamases,
      there are considerable differences in the shape of the active site tunnel.
      Modeling studies suggest steric factors to account for the enzyme's selectivity
      for ester hydrolysis versus beta-lactam cleavage.

PMID- 11847271
TI  - Structure of variant 2 scorpion toxin from Centruroides sculpturatus Ewing.
AB  - Centruroides sculpturatus Ewing variant 2 toxin (CsE-v2) is a neurotoxin isolated
      from the venom of a scorpion native to the Arizona desert. The structure of CsE
      v2 was solved in two different crystal forms using a combination of molecular
      replacement and multiple isomorphous replacement techniques. Crystals of CsE-v2
      display a temperature-dependent, reversible-phase transition near room
      temperature. At lower temperature the space group changes from P3(2)21 to P3(1)21
      with an approximate doubling of the C-axis. The small-cell structure, which has
      one molecule per asymmetric unit, has an R factor of 0.229 at 2.8 A resolution.
      The large-cell structure has two molecules per asymmetric unit and was refined at
      2.2 A resolution to an R factor of 0.255. CsE-v2 is a rigid, compact structure
      with four intrachain disulfide bonds. The structure is similar to other long
      chain beta neurotoxins, and the largest differences occur in the last six
      residues. The high-resolution structure of CsE-v2 corrects an error in the
      reported C-terminal sequence; the terminal tripeptide sequence is Ser 64-Cys 65
      Ser 66 rather than Ser 64-Ser 65-Cys 66. Comparison of CsE-v2 with long-chain
      alpha toxins reveals four insertions and one deletion, as well as additional
      residues at the N and C termini. Structural alignment of alpha and beta toxins
      suggests that the primary distinguishing feature between the two classes is the
      length of the loop between the second and third strands in a three-strand beta
      sheet. The shorter loop in alpha toxins exposes a critical lysine side chain,
      whereas the longer loop in beta toxins buries the corresponding basic residue
      (either arginine or lysine).

PMID- 11847272
TI  - The solution structure of human beta2-microglobulin reveals the prodromes of its
      amyloid transition.
AB  - The solution structure of human beta2-microglobulin (beta2-m), the nonpolymorphic
      component of class I major histocompatibility complex (MHC-I), was determined by
      (1)H NMR spectroscopy and restrained modeling calculations. Compared to previous
      structural data obtained from the NMR secondary structure of the isolated protein
      and the crystal structure of MHC-I, in which the protein is associated to the
      heavy-chain component, several differences are observed. The most important
      rearrangements were observed for (1) strands V and VI (loss of the C-terminal and
      N-terminal end, respectively), (2) interstrand loop V-VI, and (3) strand I,
      including the N-terminal segment (displacement outward of the molecular core).
      These modifications can be considered as the prodromes of the amyloid transition.
      Solvation of the protected regions in MHC-I decreases the tertiary packing by
      breaking the contiguity of the surface hydrophobic patches at the interface with
      heavy chain and the nearby region at the surface charge cluster of the C-terminal
      segment. As a result, the molecule is placed in a state in which even minor
      charge and solvation changes in response to pH or ionic-strength variations can
      easily compromise the hydrophobic/hydrophilic balance and trigger the transition
      into a partially unfolded intermediate that starts with unpairing of strand I and
      leads to polymerization and precipitation into fibrils or amorphous aggregates.
      The same mechanism accounts for the partial unfolding and fiber formation
      subsequent to Cu(2+) binding, which is shown to occur primarily at His 31 and
      involve partially also His 13, the next available His residue along the partial
      unfolding pathway.

PMID- 11847273
TI  - Single-domain antibody fragments with high conformational stability.
AB  - A variety of techniques, including high-pressure unfolding monitored by Fourier
      transform infrared spectroscopy, fluorescence, circular dichroism, and surface
      plasmon resonance spectroscopy, have been used to investigate the equilibrium
      folding properties of six single-domain antigen binders derived from camelid
      heavy-chain antibodies with specificities for lysozymes, beta-lactamases, and a
      dye (RR6). Various denaturing conditions (guanidinium chloride, urea,
      temperature, and pressure) provided complementary and independent methods for
      characterizing the stability and unfolding properties of the antibody fragments.
      With all binders, complete recovery of the biological activity after renaturation
      demonstrates that chemical-induced unfolding is fully reversible. Furthermore,
      denaturation experiments followed by optical spectroscopic methods and affinity
      measurements indicate that the antibody fragments are unfolded cooperatively in a
      single transition. Thus, unfolding/refolding equilibrium proceeds via a simple
      two-state mechanism (N <--> U), where only the native and the denatured states
      are significantly populated. Thermally-induced denaturation, however, is not
      completely reversible, and the partial loss of binding capacity might be due, at
      least in part, to incorrect refolding of the long loops (CDRs), which are
      responsible for antigen recognition. Most interestingly, all the fragments are
      rather resistant to heat-induced denaturation (apparent T(m) = 60-80 degrees C),
      and display high conformational stabilities (DeltaG(H(2)O) = 30-60 kJ mole(-1)).
      Such high thermodynamic stability has never been reported for any functional
      conventional antibody fragment, even when engineered antigen binders are
      considered. Hence, the reduced size, improved solubility, and higher stability of
      the camelid heavy-chain antibody fragments are of special interest for
      biotechnological and medical applications.

PMID- 11847274
TI  - A test of proposed rules for helix capping: implications for protein design.
AB  - alpha-helices within proteins are often terminated (capped) by distinctive
      configurations of the polypeptide chain. Two common arrangements are the
      Schellman motif and the alternative alpha(L) motif. Rose and coworkers developed
      stereochemical rules to identify the locations of such motifs in proteins of
      unknown structure based only on their amino acid sequences. To check the
      effectiveness of these rules, they made specific predictions regarding the
      structural and thermodynamic consequences of certain mutations in T4 lysozyme. We
      have constructed these mutants and show here that they have neither the structure
      nor the stability that was predicted. The results show the complexity of the
      protein-folding problem. Comparison of known protein structures may show that a
      characteristic sequence of amino acids (a sequence motif) corresponds to a
      conserved structural motif. In any particular protein, however, changes in other
      parts of the sequence may result in a different conformation. The structure is
      determined by sequence as a whole, not by parts considered in isolation.

PMID- 11847275
TI  - Propagation of a single destabilizing mutation throughout the Escherichia coli
      ribonuclease HI native state.
AB  - A point mutation (I53A) in the core of Escherichia coli RNase H* is known to
      destabilize both the native conformation (DeltaG(UN)) and the kinetic
      intermediate (DeltaG(UI)) by 2 kcal/mole. Here, we have used native-state
      hydrogen deuterium exchange to ask how this destabilization is propagated
      throughout the molecule. Stability parameters were obtained for individual
      residues in I53A and compared with those from the wild-type protein. A
      destabilization of 2 kcal/mole was observed in residues in the core but was not
      detected in the periphery of the molecule. These results are consistent with the
      localized destabilization of the core observed in the early intermediate of the
      kinetic folding pathway, supporting the resemblance of this kinetic intermediate
      to the partially unfolded form detected in the native state at equilibrium. A
      thermodynamic cycle also shows no interaction between Ile 53 and a residue in the
      periphery. There is, however, an increase in the number of denaturant-independent
      exchange events in the periphery of I53A, showing that effects of the point
      mutation are communicated to regions outside the core, although perhaps not
      through changes in stability. In sum, this work shows that localized regions
      within a protein can be destabilized independently. Furthermore, it implies a
      correspondence between the kinetic intermediate and the equilibrium PUF, as the
      magnitude and localization of the destabilization are the same in both.

PMID- 11847276
TI  - Nef of HIV-1 interacts directly with calcium-bound calmodulin.
AB  - It was recently found that the myristoyl group of CAP-23/NAP-22, a neuron
      specific protein kinase C substrate, is essential for the interaction between the
      protein and Ca(2+)-bound calmodulin (Ca(2+)/CaM). Based on the N-terminal amino
      acid sequence alignment of CAP-23/NAP-22 and other myristoylated proteins,
      including the Nef protein from human immunodeficiency virus (HIV), we proposed a
      new hypothesis that the protein myristoylation plays important roles in protein
      calmodulin interactions. To investigate the possibility of direct interaction
      between Nef and calmodulin, we performed structural studies of Ca(2+)/CaM in the
      presence of a myristoylated peptide corresponding to the N-terminal region of
      Nef. The dissociation constant between Ca(2+)/CaM and the myristoylated Nef
      peptide was determined to be 13.7 nM by fluorescence spectroscopy analyses. The
      NMR experiments indicated that the chemical shifts of some residues on and around
      the hydrophobic clefts of Ca(2+)/CaM changed markedly in the Ca(2+)/CaM-Nef
      peptide complex with the molar ratio of 1:2. Correspondingly, the radius of
      gyration determined by the small angle X-ray scattering measurements is 2-3 A
      smaller that of Ca(2+)/CaM alone. These results demonstrate clearly that Nef
      interacts directly with Ca(2+)/CaM.

PMID- 11847277
TI  - Structural insights into human serum albumin-mediated prostaglandin catalysis.
AB  - Previous studies have shown that many arachidonic acid metabolites bind to human
      serum albumin (HSA) and that the metabolism of these molecules is altered as a
      result of binding. The present study attempted to gain insights into the
      mechanisms by which prostaglandins bound to subdomain 2A of HSA are metabolized
      by catalytic processes. The breakdown of the prostaglandin 15-keto-PGE(2) to 15
      keto-PGA(2) and 15-keto-PGB(2) in the presence of wild-type HSA and a number of
      subdomain 2A mutants was examined using a previously validated spectroscopic
      method which monitors absorbance at 505 nm. The species examined using this
      method were wild-type HSA, K195M, K199M, F211V, W214L, R218M, R218P, R218H,
      R222M, H242V, R257M, and bovine serum albumin. Previous studies of HSA-mediated
      catalysis indicated that the breakdown of HSA-bound prostaglandins results from
      an alkaline microenvironment in the binding site. Our results show that the
      catalytic breakdown of HSA-bound 15-keto-PGE(2) to 15-keto-PGB(2) results from
      two specific processes which are modulated by specific amino acid residues.
      Specifically, some amino acid residues modulate the rate of step 1, the
      conversion of 15-keto-PGE(2) to 15-keto-PGA(2), while other residues modulate the
      rate of step 2, the conversion of 15-keto-PGA(2) to 15-keto-PGB(2). Some residues
      modulate the rate of steps 1 and 2. In total, while our results support the
      involvement of certain basic amino acid residues in the catabolism of HSA-bound
      15-keto-PGE(2), our data suggest that metabolism of HSA-bound prostaglandins may
      be a more complex and specific process than previously thought.

PMID- 11847278
TI  - Expression, purification, and activities of full-length and truncated versions of
      the integral membrane protein Vpu from HIV-1.
AB  - Vpu is an 81-residue accessory protein of HIV-1. Because it is a membrane
      protein, it presents substantial technical challenges for the characterization of
      its structure and function, which are of considerable interest because the
      protein enhances the release of new virus particles from cells infected with HIV
      1 and induces the intracellular degradation of the CD4 receptor protein. The Vpu
      mediated enhancement of the virus release rate from HIV-1-infected cells is
      correlated with the expression of an ion channel activity associated with the
      transmembrane hydrophobic helical domain. Vpu-induced CD4 degradation and, to a
      lesser extent, enhancement of particle release are both dependent on the
      phosphorylation of two highly conserved serine residues in the cytoplasmic domain
      of Vpu. To define the minimal folding units of Vpu and to identify their
      activities, we prepared three truncated forms of Vpu and compared their
      structural and functional properties to those of full-length Vpu (residues 2-81).
      Vpu(2-37) encompasses the N-terminal transmembrane alpha-helix; Vpu(2-51) spans
      the N-terminal transmembrane helix and the first cytoplasmic alpha-helix; Vpu(28
      81) includes the entire cytoplasmic domain containing the two C-terminal
      amphipathic alpha-helices without the transmembrane helix. Uniformly isotopically
      labeled samples of the polypeptides derived from Vpu were prepared by expression
      of fusion proteins in E. coli and were studied in the model membrane environments
      of lipid micelles by solution NMR spectroscopy and oriented lipid bilayers by
      solid-state NMR spectroscopy. The assignment of backbone resonances enabled the
      secondary structure of the constructs corresponding to the transmembrane and the
      cytoplasmic domains of Vpu to be defined in micelle samples by solution NMR
      spectroscopy. Solid-state NMR spectra of the polypeptides in oriented lipid
      bilayers demonstrated that the topology of the domains is retained in the
      truncated polypeptides. The biological activities of the constructs of Vpu were
      evaluated. The ion channel activity is confined to the transmembrane alpha-helix.
      The C-terminal alpha-helices modulate or promote the oligomerization of Vpu in
      the membrane and stabilize the conductive state of the channel, in addition to
      their involvement in CD4 degradation.

PMID- 11847279
TI  - Binding specificity and the ligand dissociation process in the E. coli biotin
      holoenzyme synthetase.
AB  - The binding of the Escherichia coli biotin holoenzyme synthetase to the two
      ligands, biotin and bio-5'-AMP, is coupled to disorder-to-order transitions in
      the protein. In the structure of the biotin complex, a "glycine-rich" loop that
      is disordered in the apo-enzyme is folded over the ligand. Mutations in three
      residues in this loop result in significant changes in the affinity of the enzyme
      for both biotin and bio-5'-AMP. The kinetic basis of these losses in the affinity
      resides primarily in changes in the unimolecular rates of dissociation of the
      complexes. In this work, isothermal titration calorimetry has been employed to
      examine the detailed thermodynamics of binding of three loop mutants to biotin
      and bio-5'-AMP. The energetic features of dissociation of the protein*ligand
      complexes also have been probed by measuring the temperature dependencies of the
      unimolecular dissociation rates. Analysis of the data using the Eyring formalism
      yielded entropic and enthalpic contributions to the energetic barrier to
      dissociation. The thermodynamic results coupled with the known structures of the
      apo-enzyme and biotin complex have been used to formulate a model for progression
      from the ground-state complex to the transition state in biotin dissociation. In
      this model, the transition-state is characterized by both partial disruption of
      noncovalent bonds and acquisition of some of the disorder that characterizes the
      glycine-rich loop in the absence of ligand.

PMID- 11847280
TI  - Electrostatics in protein-protein docking.
AB  - A novel geometric-electrostatic docking algorithm is presented, which tests and
      quantifies the electrostatic complementarity of the molecular surfaces together
      with the shape complementarity. We represent each molecule to be docked as a grid
      of complex numbers, storing information regarding the shape of the molecule in
      the real part and information regarding the electrostatic character of the
      molecule in the imaginary part. The electrostatic descriptors are derived from
      the electrostatic potential of the molecule. Thus, the electrostatic character of
      the molecule is represented as patches of positive, neutral, or negative values.
      The potential for each molecule is calculated only once and stored as potential
      spheres adequate for exhaustive rotation/translation scans. The geometric
      electrostatic docking algorithm is applied to 17 systems, starting form the
      structures of the unbound molecules. The results-in terms of the complementarity
      scores of the nearly correct solutions, their ranking in the lists of sorted
      solutions, and their statistical uniqueness-are compared with those of geometric
      docking, showing that the inclusion of electrostatic complementarity in docking
      is very important, in particular in docking of unbound structures. Based on our
      results, we formulate several "good electrostatic docking rules": The geometric
      electrostatic docking procedure is more successful than geometric docking when
      the potential patches are large and when the potential extends away from the
      molecular surface and protrudes into the solvent. In contrast, geometric docking
      is recommended when the electrostatic potential around the molecules to be docked
      appears homogeneous, that is, with a similar sign all around the molecule.

PMID- 11847281
TI  - High probability of disrupting a disulphide bridge mediated by an endogenous
      excited tryptophan residue.
AB  - It is well known that ultraviolet (UV) radiation may reduce or even abolish the
      biological activity of proteins and enzymes. UV light, as a component of
      sunlight, is illuminating all light-exposed parts of living organisms, partly
      composed of proteins and enzymes. Although a considerable amount of empirical
      evidence for UV damage has been compiled, no deeper understanding of this
      important phenomenon has yet emerged. The present paper presents a detailed
      analysis of a classical example of UV-induced changes in three-dimensional
      structure and activity of a model enzyme, cutinase from Fusarium solani pisi. The
      effect of illumination duration and power has been investigated. A photon-induced
      mechanism responsible for structural and functional changes is proposed.
      Tryptophan excitation energy disrupts a neighboring disulphide bridge, which in
      turn leads to altered biological activity and stability. The loss of the
      disulphide bridge has a pronounced effect on the fluorescence quantum yield,
      which has been monitored as a function of illumination power. A general
      theoretical model for slow two-state chemical exchange is formulated, which
      allows for calculation of both the mean number of photons involved in the process
      and the ratio between the quantum yields of the two states. It is clear from the
      present data that the likelihood for UV damage of proteins is directly
      proportional to the intensity of the UV radiation. Consistent with the loss of
      the disulphide bridge, a complex pH-dependent change in the fluorescence
      lifetimes is observed. Earlier studies in this laboratory indicate that proteins
      are prone to such UV-induced radiation damage because tryptophan residues
      typically are located as next spatial neighbors to disulphide bridges. We believe
      that these observations may have far-reaching implications for protein stability
      and for assessing the true risks involved in increasing UV radiation loads on
      living organisms.

PMID- 11847282
TI  - Independent tyrosyl contributions to the CD of Ff gene 5 protein and the
      distinctive effects of Y41H and Y41F mutants on protein-protein cooperative
      interactions.
AB  - The gene 5 protein (g5p) of the Ff virus contains five Tyr, individual mutants of
      which have now all been characterized by CD spectroscopy. The protein has a
      dominant tyrosyl 229-nm L(a) CD band that is shown to be approximately the sum of
      the five individual Tyr contributions. Tyr41 is particularly important in
      contributing to the high cooperativity with which the g5p binds to ssDNA, and
      Y41F and Y41H mutants are known to differ in dimer-dimer packing interactions in
      crystal structures. We compared the solution structures and binding properties of
      the Y41F and Y41H mutants using CD spectroscopy. Secondary structures of the
      mutants were similar by CD analyses and close to those derived from the crystal
      structures. However, there were significant differences in the binding properties
      of the two mutant proteins. The Y41H protein had an especially low binding
      affinity and perturbed the spectrum of poly[d(A)] in 2 mM Na(+) much less than
      did Y41F and the wild-type gene 5 proteins. Moreover, a change in the Tyr 229 nm
      band, assigned to the perturbation of Tyr34 at the dimer-dimer interface, was
      absent in titrations with the Y41H mutant under low salt conditions. In contrast,
      titrations with the Y41H mutant in 50 mM Na(+) exhibited typical CD changes of
      both the nucleic acid and the Tyr 229-nm band. Thus, protein-protein and g5p
      ssDNA interactions appeared to be mutually influenced by ionic strength,
      indicative of correlated changes in the ssDNA binding and cooperativity loops of
      the protein or of indirect structural constraints.

PMID- 11847283
TI  - Crystal structure of a cyanobacterial phytochrome response regulator.
AB  - The two-component signal transduction pathway widespread in prokaryotes, fungi,
      molds, and some plants involves an elaborate phosphorelay cascade. Rcp1 is the
      phosphate receiver module in a two-component system controlling the light
      response of cyanobacteria Synechocystis sp. via cyanobacterial phytochrome Cph1,
      which recognizes Rcp1 and transfers its phosphoryl group to an aspartate residue
      in response to light. Here we describe the crystal structure of Rcp1 refined to a
      crystallographic R-factor of 18.8% at a resolution of 1.9 A. The structure
      reveals a tightly associated homodimer with monomers comprised of doubly wound
      five-stranded parallel beta-sheets forming a single-domain protein homologous
      with the N-terminal activator domain of other response regulators (e.g.,
      chemotaxis protein CheY). The three-dimensional structure of Rcp1 appears
      consistent with the conserved activation mechanism of phosphate receiver
      proteins, although in this case, the C-terminal half of its regulatory domain,
      which undergoes structural changes upon phosphorylation, contributes to the
      dimerization interface. The involvement of the residues undergoing
      phosphorylation-induced conformational changes at the dimeric interface suggests
      that dimerization of Rcp1 may be regulated by phosphorylation, which could affect
      the interaction of Rcp1 with downstream target molecules.

PMID- 11847284
TI  - Crystal structure of human L-isoaspartyl-O-methyl-transferase with S-adenosyl
      homocysteine at 1.6-A resolution and modeling of an isoaspartyl-containing
      peptide at the active site.
AB  - Spontaneous formation of isoaspartyl residues (isoAsp) disrupts the structure and
      function of many normal proteins. Protein isoaspartyl methyltransferase (PIMT)
      reverts many isoAsp residues to aspartate as a protein repair process. We have
      determined the crystal structure of human protein isoaspartyl methyltransferase
      (HPIMT) complexed with adenosyl homocysteine (AdoHcy) to 1.6-A resolution. The
      core structure has a nucleotide binding domain motif, which is structurally
      homologous with the N-terminal domain of the bacterial Thermotoga maritima PIMT.
      Highly conserved residues in PIMTs among different phyla are placed at positions
      critical to AdoHcy binding and orienting the isoAsp residue substrate for
      methylation. The AdoHcy is completely enclosed within the HPIMT and a
      conformational change must occur to allow exchange with adenosyl methionine
      (AdoMet). An ordered sequential enzyme mechanism is supported because C-terminal
      residues involved with AdoHcy binding also form the isoAsp peptide binding site,
      and a change of conformation to allow AdoHcy to escape would preclude peptide
      binding. Modeling experiments indicated isoAsp groups observed in some known
      protein crystal structures could bind to the HPIMT active site.

PMID- 11847286
TI  - Structural basis for abrogated binding between staphylococcal enterotoxin A
      superantigen vaccine and MHC-IIalpha.
AB  - Staphylococcal enterotoxins (SEs) are superantigenic protein toxins responsible
      for a number of life-threatening diseases. The X-ray structure of a
      staphylococcal enterotoxin A (SEA) triple-mutant (L48R, D70R, and Y92A) vaccine
      reveals a cascade of structural rearrangements located in three loop regions
      essential for binding the alpha subunit of major histocompatibility complex class
      II (MHC-II) molecules. A comparison of hypothetical model complexes between SEA
      and the SEA triple mutant with MHC-II HLA-DR1 clearly shows disruption of key
      ionic and hydrophobic interactions necessary for forming the complex. Extensive
      dislocation of the disulfide loop in particular interferes with MHC-IIalpha
      binding. The triple-mutant structure provides new insights into the loss of
      superantigenicity and toxicity of an engineered superantigen and provides a basis
      for further design of enterotoxin vaccines.

PMID- 11847285
TI  - Short-chain dehydrogenase/reductase (SDR) relationships: a large family with
      eight clusters common to human, animal, and plant genomes.
AB  - The progress in genome characterizations has opened new routes for studying
      enzyme families. The availability of the human genome enabled us to delineate the
      large family of short-chain dehydrogenase/reductase (SDR) members. Although the
      human genome releases are not yet final, we have already found 63 members. We
      have also compared these SDR forms with those of three model organisms:
      Caenorhabditis elegans, Drosophila melanogaster, and Arabidopsis thaliana. We
      detect eight SDR ortholog clusters in a cross-genome comparison. Four of these
      clusters represent extended SDR forms, a subgroup found in all life forms. The
      other four are classical SDRs with activities involved in cellular
      differentiation and signalling. We also find 18 SDR genes that are present only
      in the human genome of the four genomes studied, reflecting enzyme forms specific
      to mammals. Close to half of these gene products represent steroid
      dehydrogenases, emphasizing the regulatory importance of these enzymes.

PMID- 11847287
TI  - Improved detection of homologous membrane proteins by inclusion of information
      from topology predictions.
AB  - A total of 20%-25% of the proteins in a typical genome are helical membrane
      proteins. The transmembrane regions of these proteins have markedly different
      properties when compared with globular proteins. This presents a problem when
      homology search algorithms optimized for globular proteins are applied to
      membrane proteins. Here we present modifications of the standard Smith-Waterman
      and profile search algorithms that significantly improve the detection of related
      membrane proteins. The improvement is based on the inclusion of information about
      predicted transmembrane segments in the alignment algorithm. This is done by
      simply increasing the alignment score if two residues predicted to belong to
      transmembrane segments are aligned with each other. Benchmarking over a test set
      of G-protein-coupled receptor sequences shows that the number of false positives
      is significantly reduced in this way, both when closely related and distantly
      related proteins are searched for.

PMID- 11847288
TI  - The distinctive functions of the two structural calcium atoms in bovine
      pancreatic deoxyribonuclease.
AB  - The two amino acid residues, Asp 99 and Asp 201, involved in the coordination of
      the two calcium atoms in the X-ray structure of bovine pancreatic (bp) DNase,
      were individually changed by site-directed mutagenesis. The two altered proteins,
      brDNase(D99A) and brDNase(D201A) were expressed in Escherichia coli and purified
      by anion exchange chromatography. Equilibrium dialysis showed that mutation
      destroyed one Ca(2+)-binding site each in brDNase(D99A) and brDNase(D201A).
      Compared with bpDNase, the Vmax value for brDNase(D99A) remained unchanged and
      that for brDNase(D201A) was decreased, whereas the K(m) values for the two
      variants were increased two- to threefold when the DNA hydrolytic hyperchromicity
      assay was used. Like bpDNase, brDNase(D99A) was able to make double scission on
      duplex DNA with Mg(2+) plus Ca(2+) and was effectively protected by Ca(2+) from
      the trypsin inactivation. But under the same conditions, brDNase(D201A) lost the
      double-scission ability and was not protected by Ca(2+). Nevertheless, the two
      variant proteins retained the characteristics of the Ca(2+)-induced
      conformational changes and the Ca(2+) protection against the beta-mercaptoethanol
      disruption of the essential disulfide bond, suggesting that other weaker Ca(2+)
      binding sites not found in the X-ray structure were responsible for these
      properties. Therefore, the two structural calcium atoms are not for maintaining
      the overall conformation of the active DNase, as it has been indicated in the X
      ray analysis, but rather play the role in the fine-tuning of the DNase activity.

PMID- 11847289
TI  - Conserved and nonconserved features of the folding pathway of hisactophilin, a
      beta-trefoil protein.
AB  - Based on previous studies of interleukin-1beta (IL-1beta) and both acidic and
      basic fibroblast growth factors (FGFs), it has been suggested that the folding of
      beta-trefoil proteins is intrinsically slow and may occur via the formation of
      essential intermediates. Using optical and NMR-detected quenched-flow
      hydrogen/deuterium exchange methods, we have measured the folding kinetics of
      hisactophilin, another beta-trefoil protein that has < 10% sequence identity and
      unrelated function to IL-1beta and FGFs. We find that hisactophilin can fold
      rapidly and with apparently two-state kinetics, except under the most stabilizing
      conditions investigated where there is evidence for formation of a folding
      intermediate. The hisactophilin intermediate has significant structural
      similarities to the IL-1beta intermediate that has been observed experimentally
      and predicted theoretically using a simple, topology-based folding model;
      however, it appears to be different from the folding intermediate observed
      experimentally for acidic FGF. For hisactophilin and acidic FGF, intermediates
      are much less prominent during folding than for IL-1beta. Considering the
      structures of the different beta-trefoil proteins, it appears that differences in
      nonconserved loops and hydrophobic interactions may play an important role in
      differential stabilization of the intermediates for these proteins.

PMID- 11847290
TI  - The role of aromatic residues in the hydrophobic core of the villin headpiece
      subdomain.
AB  - Small autonomously folding proteins are of interest as model systems to study
      protein folding, as the same molecule can be used for both experimental and
      computational approaches. The question remains as to how well these minimized
      peptide model systems represent larger native proteins. For example, is the core
      of a minimized protein tolerant to mutation like larger proteins are? Also, do
      minimized proteins use special strategies for specifying and stabilizing their
      folded structure? Here we examine these questions in the 35-residue autonomously
      folding villin headpiece subdomain (VHP subdomain). Specifically, we focus on a
      cluster of three conserved phenylalanine (F) residues F47, F51, and F58, that
      form most of the hydrophobic core. These three residues are oriented such that
      they may provide stabilizing aromatic-aromatic interactions that could be
      critical for specifying the fold. Circular dichroism and 1D-NMR spectroscopy show
      that point mutations that individually replace any of these three residues with
      leucine were destabilized, but retained the native VHP subdomain fold. In pair
      wise replacements, the double mutant that retains F58 can adopt the native fold,
      while the two double mutants that lack F58 cannot. The folding of the double
      mutant that retains F58 demonstrates that aromatic-aromatic interactions within
      the aromatic cluster are not essential for specifying the VHP subdomain fold. The
      ability of the VHP subdomain to tolerate mutations within its hydrophobic core
      indicates that the information specifying the three dimensional structure is
      distributed throughout the sequence, as observed in larger proteins. Thus, the
      VHP subdomain is a legitimate model for larger, native proteins.

PMID- 11847291
TI  - Evaluation of the energetic contribution of an ionic network to beta-sheet
      stability.
AB  - We have evaluated the interaction energy of a three-residue ionic network
      constructed on the beta-sheet surface of protein G using double mutant cycles.
      Although the two individual ion pairs were each stabilizing by 0.6 kcal/mol, the
      excess gain in stability for the triad was small (0.06 kcal/mol).

PMID- 11847292
TI  - Breaking the singleton of germination protease.
AB  - Germination protease (GPR) plays an important role in the germination of spores
      of Bacillus and Clostridium species. A few very similar GPRs form a singleton
      group without significant sequence similarities to any other proteins. Their
      active site locations and catalytic mechanisms are unclear, despite the recent 3
      D structure determination of Bacillus megaterium GPR. Using structural comparison
      and sequence analysis, we show that GPR is homologous to bacterial hydrogenase
      maturation protease (HybD). HybD's activity relies on the recognition and binding
      of metal ions in Ni-Fe hydrogenase, its substrate. Two highly conserved motifs
      are shared among GPRs, hydrogenase maturation proteases, and another group of
      hypothetical proteins. Conservation of two acidic residues in all these homologs
      indicates that metal binding is important for their function. Our analysis helps
      localize the active site of GPRs and provides insight into the catalytic
      mechanisms of a superfamily of putative metal-regulated proteases.

PMID- 11847294
TI  - Functional control of the binuclear metal site in the metallo-beta-lactamase-like
      fold by subtle amino acid replacements.
AB  - At present there are three protein families that share a common structural
      domain, the alphabeta/betaalpha fold of class B beta-lactamases: zinc beta
      lactamases, glyoxalases II, and A-type flavoproteins. A detailed inspection of
      their superimposed structures was undertaken and showed that although these
      proteins contain binuclear metal sites in spatially equivalent positions, there
      are some subtle differences within the first ligand sphere that determine a
      distinct composition of metals. Although zinc beta-lactamases contain either a
      mono or a di-zinc center, the catalytically active form of glyoxalase II contains
      a mixed iron-zinc binuclear center, whereas A-type flavoproteins contain a di
      iron site. These variations on the type of metal site found within a common fold
      are correlated with the subtle variations in the nature of the ligating amino
      acid residues and are discussed in terms of the different reactions catalyzed by
      each of the protein families. Correlation of these observations with sequence
      data results in the definition of a sequence motif that comprises the possible
      binuclear metal site ligands in this broad family. The evolution of the proteins
      sharing this common fold and factors modulating reactivity are also discussed.

PMID- 11847296
TI  - The Surgeon General's Blueprint for Action on Breastfeeding.

PMID- 11847293
TI  - Generation of ligand-receptor alliances by "SEA" module-mediated cleavage of
      membrane-associated mucin proteins.
AB  - A mechanism is described whereby one and the same gene can encode both a receptor
      protein as well as its specific ligand. Generation of this receptor-ligand
      partnership is effected by proteolytic cleavage within a specific module located
      in a membrane resident protein. It is postulated here that the "SEA" module,
      found in a number of heavily O-linked glycosylated membrane-associated proteins,
      serves as a site for proteolytic cleavage. The subunits generated by proteolytic
      cleavage of the SEA module reassociate, and can subsequently elicit a signaling
      cascade. We hypothesize that all membrane resident proteins containing such a
      "SEA" module will undergo cleavage, thereby generating a receptor-ligand
      alliance. This requires that the protein subunits resulting from the proteolytic
      cleavage reassociate with each other in a highly specific fashion. The same SEA
      module that serves as the site for proteolytic cleavage, probably also contains
      the binding sites for reassociation of the resultant two subunits. More than one
      type of module can function as a site for proteolytic cleavage; this can occur
      not only in one-pass membrane proteins but also in 7-transmembrane proteins and
      other membrane-associated proteins. The proposal presented here is likely to have
      significant practical consequences. It could well lead to the rational design and
      identification of molecules that, by binding to one of the cleaved partners, will
      act either as agonists or antagonists, alter signal transduction and, hence,
      cellular behavior.

PMID- 11847297
TI  - Measuring community bicycle helmet use among children.
AB  - Bicycling is a popular recreational activity and a principal mode of
      transportation for children in the United States, yet about 300 children die and
      430,000 are injured annually. Wearing a bicycle helmet is an important
      countermeasure, since it reduces the risk of serious brain injury by up to 85%.
      The Centers for Disease Control and Prevention (CDC) have funded state health
      departments to conduct bicycle helmet programs, and their effectiveness has been
      evaluated by monitoring community bicycle helmet use. Although it would appear
      that measuring bicycle helmet use is easy, it is actually neither simple nor
      straightforward. The authors describe what they have learned about assessing
      helmet use and what methods have been most useful. They also detail several key
      practical decisions that define the current CDC position regarding helmet use
      assessment. Although important enough in their own right, the lessons learned in
      the CDC's bicycle helmet evaluation may serve as a model for evaluating other
      injury prevention and public health programs.

PMID- 11847298
TI  - A public health response to emerging technology: expansion of the Massachusetts
      newborn screening program.
AB  - The development of a new technology, called tandem mass spectrometry (tandem MS),
      has challenged governments worldwide to consider expanding universal newborn
      screening for rare metabolic disorders. In 1997 the Massachusetts Department of
      Public Health developed a public process to meet this challenge. After addressing
      significant medical, legal, ethical, and logistical issues raised by tandem MS,
      Massachusetts incorporated one new disorder into the mandatory newborn screen and
      developed an optional pilot program for 20 additional disorders. The
      Massachusetts experience has wide relevance for other nations and states. As
      screening protocols are contemplated for entire populations-for newborns and
      others- it will remain essential that the public participate in an open process
      of reviewing the justification for and logistics of screening.

PMID- 11847299
TI  - Accessing population health information through interactive systems: lessons
      learned and future directions.
AB  - In the mid-1990s, several state and county public health departments implemented
      interactive software systems that provided easy access to public health-related
      data for local boards of health, other public health agencies, health care
      providers, community groups, and other interested members of the public. Based on
      their experiences with two well-established state interactive systems and one
      well-established county system, the authors summarize lessons that could prove
      useful to state and local public health agencies interested in developing new
      interactive systems or adapting existing ones. The article addresses issues such
      as: basing interactive systems on a broad definition of health, designing systems
      to incorporate user preferences, moving from data warehouses to information
      warehouses, and fostering prevention communities. Finally, the article provides
      recommendations to assist federal, state, and local public health agencies in
      developing the next generation of interactive data access systems.

PMID- 11847301
TI  - Who's number one? The impact of variability on rankings based on public health
      indicators.
AB  - OBJECTIVE: Researchers, government, and the press often rank jurisdictions
      according to public health indicators; however, measures of uncertainty rarely
      accompany these comparisons. To demonstrate the variability associated with
      rankings that use public health measures, the authors examined the uncertainty
      associated with ranks based on three common methods used to derive public health
      indicators: age-adjustment, calculations based on census estimates, and
      calculations based on survey data. METHODS: The authors observed the effect of
      changing the standard population from the 1970 population to the 1997 population
      on rank-order lists of jurisdictions according to age-adjusted 1998 mortality
      rates. They used a Monte Carlo method to calculate confidence intervals (CIs)
      around ranks based on census estimates of 1998 infant mortality rates and based
      on 1999 Behavioral Risk Factor Surveillance System (BRFSS) survey data on the
      prevalence of hypertension. RESULTS: Changing the standard year from 1970 to 1997
      resulted in a shift of at least three rank-order positions for seven states. Two
      states shifted five positions. CIs associated with ranking by infant mortality
      rates were broad, with a mean of 16 ranks. CIs around ranks for the prevalence of
      hypertension were also wide, with a mean of 18 ranks. CONCLUSION: While ranking
      based on public health indicators is an attractive and popular way of presenting
      public health data, caution and close examination of the underlying data are
      needed for proper interpretation. Alternative methods, such as longitudinal
      analysis or comparisons with standards, may prove more useful.

PMID- 11847300
TI  - Asthma and smoking status in a population-based study of California adults.
AB  - OBJECTIVE: Because they experience respiratory symptoms, adults with asthma might
      be expected to avoid cigarette smoking. However, previous studies have not
      adequately addressed whether adults with asthma have a lower prevalence of
      smoking than the general population. The authors sought to determine whether
      adult asthmatics are less likely to smoke cigarettes than members of the general
      population. METHODS: The authors used data from a random sample of 2,902
      California adults ages 18 years or older,with oversampling of African Americans,
      Asian/Pacific Islanders, adults with disabilities, and adults aged 45 to 70
      years. Sampling weights were used in all analyses. In this cross-sectional study,
      217 participants (7.5%) reported a physician diagnosis of asthma. RESULTS: The
      prevalence of "ever smoking" was similar among adults with asthma (48.3%) and
      those without asthma (43.0%) (risk difference 5.3%; 95% CI -1.6%, 12.2%). There
      was also no difference in the prevalence of "current smoking" among adults with
      asthma (20.2%) compared with the non-asthmatic subjects (18.8%) (risk difference
      1.4%; 95% CI -4.2%, 6.9%). After controlling for age, gender, race, and
      education, there was no evidence that adults with asthma were less likely to ever
      smoke. Although the confidence intervals did not exclude "no association," asthma
      was actually associated with an increased risk of ever smoking (OR 1.3; 95% CI
      1.0, 1.8). There was also no association between asthma and the risk of current
      smoking after controlling for covariates (OR 1.1; 95% CI 0.8, 1.6). Moreover,
      there were no differences in "age of smoking initiation," "duration of smoking,"
      or "intensity of smoking" after adjusting for demographic characteristics.
      Redefining the referent group to exclude respondents with other chronic lung
      diseases did not appreciably change study conclusions. CONCLUSION: Adults with
      asthma do not appear to selectively avoid cigarette smoking. Specific smoking
      prevention and cessation efforts should be targeted to adults with asthma.

PMID- 11847302
TI  - Cost-effectiveness of preimmunization hepatitis B screening in high-risk
      adolescents.
AB  - OBJECTIVE: The goals of this study were to estimate seroprevalence of prior
      hepatitis B infection among high-risk adolescents and to determine the cost
      effectiveness of prevaccination immunity screening. METHODS: The authors computed
      a "break-even" seroprevalence level calculated from current vaccine and
      administration costs. They then conducted a seroprevalence study of hepatitis B
      core antibody using sera previously submitted for syphilis serology from four
      hundred adolescent and adult clients of sexually transmitted disease clinics.
      Finally, the authors compared age group-specific seroprevalence rates to the
      computed break-even seroprevalence. RESULTS: Levels of prior hepatitis B
      infection for all age groups were lower than the break-even seroprevalence
      standard from which cost-effectiveness was calculated. CONCLUSIONS: From the
      findings of this study, the authors concluded that routine preimmunization
      screening for prior hepatitis B infection would not be cost-effective for this
      population.

PMID- 11847303
TI  - Assisting states in assessing newborn screening options.

PMID- 11847306
TI  - ASPH report.

PMID- 11847307
TI  - The RAR1 interactor SGT1, an essential component of R gene-triggered disease
      resistance.
AB  - Plant disease resistance (R) genes trigger innate immune responses upon pathogen
      attack. RAR1 is an early convergence point in a signaling pathway engaged by
      multiple R genes. Here, we show that RAR1 interacts with plant orthologs of the
      yeast protein SGT1, an essential regulator in the cell cycle. Silencing the
      barley gene Sgt1 reveals its role in R gene-triggered, Rar1-dependent disease
      resistance. SGT1 associates with SKP1 and CUL1, subunits of the SCF (Skp1-Cullin
      F-box) ubiquitin ligase complex. Furthermore, the RAR1-SGT1 complex also
      interacts with two COP9 signalosome components. The interactions among RAR1,
      SGT1, SCF, and signalosome subunits indicate a link between disease resistance
      and ubiquitination.

PMID- 11847308
TI  - Regulatory role of SGT1 in early R gene-mediated plant defenses.
AB  - Animal SGT1 is a component of Skp1-Cullin-F-box protein (SCF) ubiquitin ligases
      that target regulatory proteins for degradation. Mutations in one (SGT1b) of two
      highly homologous Arabidopsis SGT1 genes disable early plant defenses conferred
      by multiple resistance (R) genes. Loss of SGT1b function in resistance is not
      compensated for by SGT1a. R genes differ in their requirements for SGT1b and a
      second resistance signaling gene, RAR1, that was previously implicated as an SGT1
      interactor. Moreover, SGT1b and RAR1 contribute additively to RPP5-mediated
      pathogen recognition. These data imply both operationally distinct and
      cooperative functions of SGT1 and RAR1 in plant disease resistance.

PMID- 11847310
TI  - Tournaments, prizes--and us.

PMID- 11847309
TI  - Regulation of corepressor function by nuclear NADH.
AB  - The corepressor CtBP (carboxyl-terminal binding protein) is involved in
      transcriptional pathways important for development, cell cycle regulation, and
      transformation. We demonstrate that CtBP binding to cellular and viral
      transcriptional repressors is regulated by the nicotinamide adenine dinucleotides
      NAD+ and NADH, with NADH being two to three orders of magnitude more effective.
      Levels of free nuclear nicotinamide adenine dinucleotides, determined using two
      photon microscopy, correspond to the levels required for half-maximal CtBP
      binding and are considerably lower than those previously reported. Agents capable
      of increasing NADH levels stimulate CtBP binding to its partners in vivo and
      potentiate CtBP-mediated repression. We propose that this ability to detect
      changes in nuclear NAD+/NADH ratio allows CtBP to serve as a redox sensor for
      transcription.

PMID- 11847311
TI  - Data sharing. DNA sequencer protests being scooped with his own data.

PMID- 11847312
TI  - Infectious diseases. Researchers crack malaria genome.

PMID- 11847314
TI  - Paleontology. Earliest animal tracks or just mud cracks?

PMID- 11847315
TI  - Biomedical ethics. Study of brain dead sparks debate.

PMID- 11847313
TI  - Infectious diseases. Candidate drug breaks down malaria's walls.

PMID- 11847316
TI  - Nuclear history. Letters aver physicist supported Nazi bomb.

PMID- 11847317
TI  - United Kingdom. Parliament takes aim at Royal Society.

PMID- 11847318
TI  - Paleontology. Tug-of-war over mystery fossil.

PMID- 11847319
TI  - Homestake mine. Neutrino lab detects heavy political fallout.

PMID- 11847320
TI  - Becoming human. In search of the first hominids.

PMID- 11847321
TI  - Becoming human. New fossils raise molecular questions.

PMID- 11847322
TI  - Becoming human. What made humans modern?

PMID- 11847323
TI  - Becoming human. Why get smart?

PMID- 11847324
TI  - Genetics. Please don't call it cloning!

PMID- 11847325
TI  - Pinatubo eruption. "To make grow".

PMID- 11847326
TI  - Pinatubo eruption. The climatic aftermath.

PMID- 11847327
TI  - Immunology. One AID to unite them all.

PMID- 11847329
TI  - Thermoelectric materials. Smaller is cooler.

PMID- 11847328
TI  - Ecology. Species diversity--scale matters.

PMID- 11847330
TI  - Signal transduction. Scaffolding proteins--more than meets the eye.

PMID- 11847331
TI  - Evolution and biogeography of deep-sea vent and seep invertebrates.
AB  - Deep-sea hydrothermal vents and cold seeps are submarine springs where nutrient
      rich fluids emanate from the sea floor. Vent and seep ecosystems occur in a
      variety of geological settings throughout the global ocean and support food webs
      based on chemoautotrophic primary production. Most vent and seep invertebrates
      arrive at suitable habitats as larvae dispersed by deep-ocean currents. The
      recent evolution of many vent and seep invertebrate species (<100 million years
      ago) suggests that Cenozoic tectonic history and oceanic circulation patterns
      have been important in defining contemporary biogeographic patterns.

PMID- 11847332
TI  - GPS tracking of foraging albatrosses.

PMID- 11847333
TI  - X-ray imaging of shock waves generated by high-pressure fuel sprays.
AB  - Synchrotron x-radiography and a fast x-ray detector were used to record the time
      evolution of the transient fuel sprays from a high-pressure injector. A
      succession of 5.1-microsecond radiographs captured the propagation of the spray
      induced shock waves in a gaseous medium and revealed the complex nature of the
      spray hydrodynamics. The monochromatic x-radiographs also allow quantitative
      analysis of the shock waves that has been difficult if not impossible with
      optical imaging. Under injection conditions similar to those found in operating
      engines, the fuel jets can exceed supersonic speeds and result in gaseous shock
      waves.

PMID- 11847334
TI  - Protonic diffusion in high-pressure ice VII.
AB  - Near ambient pressures, molecular diffusion dominates protonic diffusion in ice.
      Theoretical studies have predicted that protonic diffusion will dominate at high
      pressures in ice. We measured the protonic diffusion coefficient for the highest
      temperature molecular phase of ice VII at 400 kelvin over its entire stable
      pressure region. The values ranged from 10(-17) to 10(-15) square meters per
      second at pressures of 10 to 63 gigapascals. The diffusion coefficients
      extrapolated to high temperatures close to the ice VII melting curve were less by
      a factor of 10(2) to 10(3) than a superionic criterion of approximately 10(-8)
      square meters per second, at which protons would diffuse freely.

PMID- 11847335
TI  - Electrical anisotropy below slow- and fast-moving plates: paleoflow in the upper
      mantle?
AB  - Upper mantle electrical conductivities can be explained by hydrogen diffusivity
      in hydrous olivine. Diffusivity enhances the conductivity of olivine
      anisotropically, making the a axis the most conductive of the three axes.
      Therefore, the hypothesis that plate motion induces lattice-preferred orientation
      of olivine can be tested with the use of long-period electromagnetic array
      measurements. Here, we compared electrical anisotropies below the slow-moving
      Fennoscandian and fast-moving Australian plates. The degree of olivine alignment
      is greater in the mantle below the Fennoscandian plate than below the Australian
      plate. This finding may indicate that convection rather than plate motion is the
      dominant deformation mechanism.

PMID- 11847336
TI  - A microphysical connection among biomass burning, cumulus clouds, and
      stratospheric moisture.
AB  - A likely causal chain is established here that connects humidity in the
      stratosphere, relative humidity near the tropical tropopause, ice crystal size in
      towering cumulus clouds, and aerosols associated with tropical biomass burning.
      The connections are revealed in satellite-observed fluctuations of each quantity
      on monthly to yearly time scales. More aerosols lead to smaller ice crystals and
      more water vapor entering the stratosphere. The connections are consistent with
      physical reasoning, probably hold on longer time scales, and may help to explain
      why stratospheric water vapor appears to have been increasing for the past five
      decades.

PMID- 11847337
TI  - Warming of the Southern Ocean since the 1950s.
AB  - Autonomous Lagrangian Circulation Explorer floats recorded temperatures in depths
      between 700 and 1100 meters in the Southern Ocean throughout the 1990s. These
      temperature records are systematically warmer than earlier hydrographic
      temperature measurements from the region, suggesting that mid-depth Southern
      Ocean temperatures have risen 0.17 degrees C between the 1950s and the 1980s.
      This warming is faster than that of the global ocean and is concentrated within
      the Antarctic Circumpolar Current, where temperature rates of change are
      comparable to Southern Ocean atmospheric temperature increases.

PMID- 11847338
TI  - Marine biodiversity hotspots and conservation priorities for tropical reefs.
AB  - Coral reefs are the most biologically diverse of shallow water marine ecosystems
      but are being degraded worldwide by human activities and climate warming.
      Analyses of the geographic ranges of 3235 species of reef fish, corals, snails,
      and lobsters revealed that between 7.2% and 53.6% of each taxon have highly
      restricted ranges, rendering them vulnerable to extinction. Restricted-range
      species are clustered into centers of endemism, like those described for
      terrestrial taxa. The 10 richest centers of endemism cover 15.8% of the world's
      coral reefs (0.012% of the oceans) but include between 44.8 and 54.2% of the
      restricted-range species. Many occur in regions where reefs are being severely
      affected by people, potentially leading to numerous extinctions. Threatened
      centers of endemism are major biodiversity hotspots, and conservation efforts
      targeted toward them could help avert the loss of tropical reef biodiversity.

PMID- 11847339
TI  - Rap1 GTPase regulation of adherens junction positioning and cell adhesion.
AB  - Cell-cell junctions are distributed evenly around the lateral circumference of
      cells within an epithelium. We find that the even distribution of adherens
      junctions is an active process that requires the small guanosine triphosphatase
      Rap1. Cells mutant for Rap1 condensed their adherens junctions to one side of the
      cell. This disrupted normal epithelial cell behavior, and mutant cell clones
      dispersed into the surrounding wild-type tissue. Rap1 is enriched at adherens
      junctions, particularly between newly divided sister cells where it may reseal
      the adherens junction ring. The regulation of adherens junction positioning could
      play a role in cell mobility and cell division.

PMID- 11847340
TI  - Role of the isthmus and FGFs in resolving the paradox of neural crest plasticity
      and prepatterning.
AB  - Cranial neural crest cells generate the distinctive bone and connective tissues
      in the vertebrate head. Classical models of craniofacial development argue that
      the neural crest is prepatterned or preprogrammed to make specific head
      structures before its migration from the neural tube. In contrast, recent studies
      in several vertebrates have provided evidence for plasticity in patterning neural
      crest populations. Using tissue transposition and molecular analyses in avian
      embryos, we reconcile these findings by demonstrating that classical manipulation
      experiments, which form the basis of the prepatterning model, involved
      transplantation of a local signaling center, the isthmic organizer. FGF8
      signaling from the isthmus alters Hoxa2 expression and consequently branchial
      arch patterning, demonstrating that neural crest cells are patterned by
      environmental signals.

PMID- 11847341
TI  - MAPKK-independent activation of p38alpha mediated by TAB1-dependent
      autophosphorylation of p38alpha.
AB  - Phosphorylation of mitogen-activated protein kinases (MAPKs) on specific tyrosine
      and threonine sites by MAP kinase kinases (MAPKKs) is thought to be the sole
      activation mechanism. Here, we report an unexpected activation mechanism for
      p38alpha MAPK that does not involve the prototypic kinase cascade. Rather it
      depends on interaction of p38alpha with TAB1 [transforming growth factor-beta
      activated protein kinase 1 (TAK1)-binding protein 1] leading to
      autophosphorylation and activation of p38alpha. We detected formation of a TRAF6
      TAB1-p38alpha complex and showed stimulus-specific TAB1-dependent and TAB1
      independent p38alpha activation. These findings suggest that alternative
      activation pathways contribute to the biological responses of p38alpha to various
      stimuli.

PMID- 11847342
TI  - Cytoskeletal regulation by the Nedd8 ubiquitin-like protein modification pathway.
AB  - The Nedd8 ubiquitin-like protein modification pathway regulates cell-cycle
      progression. Our analysis of Nedd8 requirements during Caenorhabditis elegans
      embryogenesis indicates that the cytoskeleton is another target. Nedd8
      conjugation negatively regulated contractility of the microfilament-rich cell
      cortex during pronuclear migration and again during cytokinesis. The Nedd8
      pathway also was required after meiosis to negatively regulate katanin, a
      microtubule-severing complex, permitting the assembly of a large mitotic spindle.
      We propose that Nedd8-modified cullin, as part of an E3 ubiquitin ligase complex,
      targets katanin for degradation during the transition from meiosis to mitosis.

PMID- 11847343
TI  - Regulation of brassinosteroid signaling by a GSK3/SHAGGY-like kinase.
AB  - GSK3/SHAGGY is a highly conserved serine/threonine kinase implicated in many
      signaling pathways in eukaryotes. Although many GSK3/SHAGGY-like kinases have
      been identified in plants, little is known about their functions in plant growth
      and development. Here we show that the Arabidopsis BRASSINOSTEROID-INSENSITIVE 2
      (BIN2) gene encodes a GSK3/SHAGGY-like kinase. Gain-of-function mutations within
      its coding sequence or its overexpression inhibit brassinosteroid (BR) signaling,
      resulting in plants that resemble BR-deficient and BR-response mutants. In
      contrast, reduced BIN2 expression via cosuppression partially rescues a weak BR
      signaling mutation. Thus, BIN2 acts as a negative regulator to control steroid
      signaling in plants.

PMID- 11847344
TI  - Requirement of the activation-induced deaminase (AID) gene for immunoglobulin
      gene conversion.
AB  - Three phenotypically distinct processes-somatic hypermutation, gene conversion,
      and switch recombination-remodel the functionally rearranged immunoglobulin (Ig)
      loci in B cells. Somatic hypermutation and switch recombination have recently
      been shown to depend on the activation-induced deaminase (AID) gene product.
      Here, we show that the disruption of the AID gene in the chicken B cell line DT40
      completely blocks Ig gene conversion and that this block can be complemented by
      reintroduction of the AID complementary DNA. This demonstrates that the AID
      master gene controls all B cell-specific modifications of vertebrate Ig genes.

PMID- 11847345
TI  - Capturing chromosome conformation.
AB  - We describe an approach to detect the frequency of interaction between any two
      genomic loci. Generation of a matrix of interaction frequencies between sites on
      the same or different chromosomes reveals their relative spatial disposition and
      provides information about the physical properties of the chromatin fiber. This
      methodology can be applied to the spatial organization of entire genomes in
      organisms from bacteria to human. Using the yeast Saccharomyces cerevisiae, we
      could confirm known qualitative features of chromosome organization within the
      nucleus and dynamic changes in that organization during meiosis. We also analyzed
      yeast chromosome III at the G1 stage of the cell cycle. We found that chromatin
      is highly flexible throughout. Furthermore, functionally distinct AT- and GC-rich
      domains were found to exhibit different conformations, and a population-average
      3D model of chromosome III could be determined. Chromosome III emerges as a
      contorted ring.

PMID- 11847346
TI  - A class of potent antimalarials and their specific accumulation in infected
      erythrocytes.
AB  - During asexual development within erythrocytes, malaria parasites synthesize
      considerable amounts of membrane. This activity provides an attractive target for
      chemotherapy because it is absent from mature erythrocytes. We found that
      compounds that inhibit phosphatidylcholine biosynthesis de novo from choline were
      potent antimalarial drugs. The lead compound, G25, potently inhibited in vitro
      growth of the human malaria parasites Plasmodium falciparum and P. vivax and was
      1000-fold less toxic to mammalian cell lines. A radioactive derivative
      specifically accumulated in infected erythrocytes to levels several hundredfold
      higher than in the surrounding medium, and very low dose G25 therapy completely
      cured monkeys infected with P. falciparum and P. cynomolgi.

PMID- 11847347
TI  - Midbrain control of three-dimensional head orientation.
AB  - Little is known about the neural mechanisms controlling head posture and why they
      fail in clinical syndromes like torticollis. It is well established, however,
      that the brain controls eye position by integrating eye velocity commands. By
      electrically stimulating and reversibly inactivating midbrain sites in the head
      free (nonimmobilized) monkey, we found that the interstitial nucleus of Cajal
      functions as a neural integrator for head posture. We suggest that a bilateral
      imbalance in this structure, through either direct damage or inappropriate input,
      could be one of the mechanisms underlying torticollis.

PMID- 11847349
TI  - A decade of hepatology---more refinements than breakthroughs.

PMID- 11847348
TI  - Tech.Sight. Optical sectioning--slices of life.

PMID- 11847350
TI  - A study of postural hypotension in a Chinese elderly outpatient population: are
      there really associated risk factors?
AB  - Postural hypotension is reported to be a common finding in elderly patients with
      prevalence rates from 10% to 30% having been reported. Proposed risk factors for
      the development of postural hypotension in the elderly include a number of
      medical conditions and medications. However, little is known about Chinses
      populations. From July 1995 through November 1995, we conducted a cross-sectional
      study on a group of 400 elderly patients (>65 years) in a geriatric outpatient
      department. Nearly 23% experienced a drop of 20 mmHg or more in systolic blood
      pressure on going from a supine to standing position. The fall did not correlate
      well with known risk factors such as use of anti-hypertensive drugs, hypnotics,
      diabetics mellitus, parkinsonism, and history of a fall. No significant factors
      were found to be associated with postural hypotension. Our data suggest that the
      change is idiopathic and does not result in any significant clinical outcome such
      as falls, syncope, and dizziness.

PMID- 11847351
TI  - Benzodiazepine prescribing trend after its inclusion as a dangerous drug under
      the Hong Kong Dangerous Drugs Ordinance.
AB  - Since January 1992, all benzodiazepines have been classified as dangerous drugs
      under the Dangerous Drugs Ordinance in Hong Kong. This legislative provision
      requires medical practitioners and pharmacists to keep a detailed record of their
      prescriptions of benzodiazepines The present study looks at the impact of the
      provision on prescribing trends in the Hong Kong population and in a general
      psychiatric clinic. A comparison of the 1991 (baseline level) and 1994 figures
      reveals a 50% and a 10% reduction in the average yearly number of benzodiazepine
      prescriptions per person in the Hong Kong population and in the general
      psychiatric clinic, respectively. In particular, triazolam prescriptions had the
      greatest reduction. The findings are discussed in light of the possible changes
      of prescribing practice by medical practitioners after the new legislative
      provision came into effect.

PMID- 11847352
TI  - A three-year review of treatment of cervical intraepithelial neoplasia with large
      loop excision of the transformation zone.
AB  - One hundred and eighty-five patients were treated with large loop excision of the
      transformation zone for cervical intraepithelial neoplasia from October 1992
      through September 1994. All patients were followed up regularly until September
      1995 to review the outcome and morbidity. Cure rates of 97.2% in the first six
      months and 95.4% at the end of the first 12 months were obtained. Thirteen
      patients (7.0%) were admitted as emergency cases for post-operative haemorrhage,
      which required suturing, cauterisation with silver nitrate or electrocoagulation,
      vaginal douching, or antibiotic treatment. One patient developed cervical
      stenosis and incomplete excisions were noted in 46 (24.9%) patients. Eleven
      (6.0%) patients had cervical carcinomas detected. Our findings further confirm
      that this method is a reliable and safe way to treat cervical intraepithelial
      neoplasia with an acceptable rate of morbidity.

PMID- 11847353
TI  - Urinary incontinence: an ignored problem in elderly patients.
AB  - Urinary incontinence is a common problem among the elderly, especially those
      admitted to acute care hospitals. A study investigating this problem was conduced
      in the geriatric wards of the Tuen Mun Hospital, Tuen Mun, from 26 October 1995
      to 9 November 1995. Fifty of 139 (36%) patients had urinary incontinence with a
      male to female ratio of 1:15. Patients with urinary incontinence were found more
      often to have mobility problems and a higher institutionalisation rate than did
      continent patients. Dementia and cerebrovascular accident were also found to be
      associated with this problem. Although it is a common problem, none had been
      evaluated or treated before. Most of the caregivers thought that urinary
      incontinence was a normal ageing process and used diapers to treat this problem.

PMID- 11847354
TI  - Health care needs in the Tai Po district of Hong Kong initial indications from a
      population-based study.
AB  - The objective of this study was to obtain a representative profile of residents
      in Tai Po district, Hong Kong, with regard to their health status, health service
      use and socio- demographic characteristics. From October 1992 to February 1993, a
      cross-sectional telephone survey of 7573 Tai Po residents was undertaken. Acute
      illness episodes in the past month, chronic illness history, and treatment
      choices for acute and chronic illnesses were used as outcomes. Socio-demographic
      data were also obtained. Seventeen per cent of respondents reported having acute
      illness in the previous month, 66% of whom attended private clinics; 5.2%
      reported having chronic illness, 58.5% of whom attended public clinics. Most
      (88.5%) acute illness sufferers who used Western medical services for acute
      illness did so within Tai Po, while 52.7% of chronic illness sufferers used
      services outside of the district. Older, female, and lower income respondents
      were more likely to use public clinics. These preliminary findings help to
      reflect the health needs of residents in Tai Po.

PMID- 11847355
TI  - Autoimmune chronic active hepatitis.
AB  - Autoimmune chronic active hepatitis, now often refereed to as simply autoimmune
      hepatitis has been recognised for nearly 50 years. Typically, the disease arises
      in a young woman who presents with an acute hepatitic illness and complains of
      lethargy, arthralgia, oligomenorrhoea, and fluctuating jaundice. For the purposes
      of clinical trials and research, guidelines for establishing the diagnosis have
      been published recently, but in clinical practise it is diagnosed when there is a
      histological picture of chronic active hepatitis together with immunological
      features (high levels of immunoglobulin G and serum autoantibodies) in the
      absence of other known causes of the histological picture. Controlled trials in
      the 1970s confirm the efficacy of immunosuppressive therapy in terms of
      improvement of both symptoms and survival. Treatment protocols based on
      prednisolone and azathioprine have been refined over the past 20 years so that
      the prognosis is now good and side effects from treatment are usually minimal.

PMID- 11847356
TI  - Surgical resection of colorectal hepatic metastases.
AB  - The reported median survival of patients with untreated colorectal liver
      metastases is 10.6 months from the time of diagnosis. Systemic and regional
      chemotherapy do produce responses in a proportion of patients but with limited
      prolongation of survival. At present, surgical resection is the only treatment
      that can cure. The 5-year survival rate following curative hepatic resection for
      colorectal liver metastases is 30% to 40%. However, only 5% to 10% of all
      patients with curative resection of their primary colon cancer will develop liver
      secondaries that are amenable to surgery. Hepatic resection for colorectal liver
      metastases should be offered to this select group of patients and should only be
      performed by an experienced surgical team with an operative mortality rate of
      less than five per cent.

PMID- 11847357
TI  - Imaging and radiological intervention in hepatocellular carcinoma.
AB  - Hepatocellular carcinoma is the second most common cause of death from malignancy
      in Hong Kong. The prognosis of patients with hepatocellular carcinoma depends on
      the hepatic function, tumour size, and tumour extent at diagnosis. Ultrasound,
      computed tomography, Lipiodal computed tomography, hepatic angiography, and
      magnetic resonance imaging are useful imaging modalities for the diagnosis of
      hepatocellular carcinomas and in assessing their operability. Transcatheter
      arterial chemoembolization, selective internal radiation therapy, and
      percutaneous transhepatic ethanol injection are promising interventional
      radiological techniques that have been introduced in the treatment of patients
      with inoperable disease. The indications for these treatment modalities and their
      efficacy are discussed.

PMID- 11847358
TI  - An update on hepatocarcinogenesis.
AB  - Hepatocellular carcinoma is the most common cancer occurring in males in the
      world and has an annual incidence worldwide of 1 million. There are variations in
      its geographical distribution. It is the second most common cancer in Southeast
      Asia, including Hong Kong and ranks third among males in China.

PMID- 11847359
TI  - Hapatitis A and E in Hong Kong.
AB  - Acute viral hepatitis is one of the most prevalent infectious diseases in Hong
      Kong and hepatitis A accounts for two thirds or more of reported cases. Improved
      sanitation has led to a decline in hepatitis A infection in childhood but more
      clinically overt adult cases now occur. Shellfish ingestion and recent travel are
      important risk factors. A highly immunogenic and effective inactivated hepatitis
      A vaccine is available. Hepatitis E is of emerging importance as a cause of acute
      hepatitis. Large outbreaks have occurred in China and other developing countries;
      sporadic cases occur in Hong Kong. High mortality is associated with hepatitis E
      complicating late pregnancy. Serological diagnosis by enzyme immunoassay for anti
      HEV is available. The education of travellers to endemic areas is advised with
      special caution being given to pregnant women. A vaccine for hepatitis E is not
      yet available.

PMID- 11847360
TI  - Infectious complications of liver transplantation.
AB  - Sixteen (50%) of the 32 patients who received liver transplantations from October
      1991 to March 1993 at Queen Mary Hospital, Hong Kong, developed viral, bacterial,
      or fungal infections. The viral infections were largely a result of
      immunosuppression while accidental bowel perforation, bile leak at the
      anastomosis, and delayed onset of stricture of the bile duct anastomosis were
      responsible for the intra-abdominal bacterial or fungal infections. Although the
      incidence of infectious complications was high, all patients were managed
      effectively and only one patient with lymphoproliferative disorder died.
      Infectious complications can lead to a prolonged hospital stay and a
      substantially increased hospital cost. The adoption of new immunosuppressive
      regimes that can better prevent acute graft rejection and adherence to meticulous
      surgical technique will help to reduce the infectious complications of liver
      transplantation in the future.

PMID- 11847361
TI  - Neurodegenerative diseases in children.
AB  - The detection of neurodegenerative and neurometabolic diseases in children relies
      on a high index of suspicion as most will present as common paediatric problems
      such as recurrent vomiting, feeding problem, failure to thrive, sepsis, or
      developmental delay. Alternatively, children may present with an acute
      encephalopathy or with a chronic progressive encephalopathy. Clinical clues
      suggestive of neurometabolic disorders include encephalopathic features such as
      microcephaly, macrocephaly, developmental regression, developmental arrest,
      change in sensorium, seizures, hypotonia, hypertonia, abnormal eye signs; also
      extrapyramidal or cerebellar signs and systemic features like abnormal
      respiration, hepatosplenomegaly, abnormal hair, liver dysfunction, renal tubular
      dysfunction, cardiomyopathy, and feeding difficulties or growth problems. Initial
      screening include tests for acidosis, ketosis, hyperlacticemia, and
      hyperammonemia. Further investigations should amino acid chromatography, assays
      of organic acids, specific enzyme assay of white cell or fibroblast culture, and
      histopatholgy of cell and tissue biopsy (white blood cell, skin, muscle,
      conjunctiva, bone marrow, liver, rectum, or brain). The correct diagnosis holds
      implications for targeted therapeutic intervention, genetic counselling, and
      possibly, prenatal diagnosis.

PMID- 11847362
TI  - A review of the rate of occurrence of cleft lip and palate in Chinese people.
AB  - Published data were used to determine the rate of occurrence of cleft lip and /or
      palate in the Chinese population. The rate of occurrence ranged from 1.33 to 2.23
      per 1000 live and stillbirths. Most studies were performed in communities with
      mixed racial groups, and only three obtained data from multiple sources. Half of
      the studies included live and still births. The majority of the studies reported
      pooled figures for subjects with and without other malformations. Furthermore,
      three different classifications of clefts were used by the authors. Clefts
      involving the lip and palate had the highest occurrence rate in most studies.
      Unfortunately, the differences in the rate of occurrence may reflect differences
      in the technique used for data collection rather than real differences.

PMID- 11847363
TI  - A rare complication of oesophageal sclerotherapy.
AB  - Endoscopic sclerotherapy is a standard procedure for the treatment of oesphageal
      varices. It is generally regarded as a safe procedure with low morbidity and
      mortality. However, there are a number of rare and fatal complications associated
      with this procedure. We report a case of pericardial effusion developing after
      oesophageal sclerotherapy. The patient developed cardiac tamponade requiring
      pericardiocentesis. This complication is uncommon, but its true incidence may be
      underestimated. When pericardial effusion is diagnosed early, this potentially
      fatal complication can be treated without serious sequelae.

PMID- 11847364
TI  - From hydrocephalus to hydrocele.
AB  - The incidence of complications associated with cerebrospinal fluid shunt
      procedures varies from low to high in different series and depending on the
      duration of follow up. We report an unusual case of four-month-old male infant
      with hydrocephalus who developed bilateral hydroceles soon after
      ventriculoperitioneal shunting. The possible aetiology is hypothesised and
      suggestions are made as to how this may be avoided in other infants undergoing
      shunt procedures.

PMID- 11847365
TI  - Recurrent hypersomina: a case report with polysomnographic findings.
AB  - Recurrent hypersomnia is an uncommon clinical problem that can be misdiagnosed
      and mistreated. I report a case of idiopathic recurrent hypersomnia. The clinical
      features, differential diagnoses, polysomnographic findings, possible
      aetiologies, and treatment are discussed.

PMID- 11847366
TI  - Lingual thyroid in a young woman.

PMID- 11847367
TI  - Caritas Medical Centre day surgery pilot study.
AB  - From April 1995 through September 1995, a day surgery pilot study was conducted
      by the Department of Surgery, Caritas Medical Centre, Hong Kong. The aim was to
      introduce the day surgery concept and to assess local patient acceptance of day
      surgery. One hundred and seventy patients, mostly below 50 years of age, were
      operated on as day surgery patients during the six months. Only two patients were
      admitted after their operations. The most common early post-operative problems
      were vomiting (15 patients) and headache (14 patients). Eighty-three per cent of
      the patients who responded to a satisfaction survey rated their overall
      satisfaction as good or excellent. In conclusion, younger patients accepted the
      day surgery concept readily and were mostly satisfied with the day surgery
      experience. Detailed pre-operative briefing and attention to case selection
      appear useful in achieving high patient acceptance and satisfaction.

PMID- 11847368
TI  - Intrathecal morphine for post-operative analgesia in patients with fractured
      hips.
AB  - This prospective, randomised, double blind study examined the efficacy of
      intrathecal morphine for post-operative analgesia in Chinese patients undergoing
      surgery to repair fractured hips. There were a total of 40 American Society of
      Anesthesiologists physical status grade I to IV patients scheduled for surgery
      following a fractured neck of the femur. Patients were randomised to a control
      group in which they received subarachnoid plain 0.5% bupivacaine, 2.2 mL, and
      normal saline, 0.4 mL, giving a total volume of 2.6 mL, or to a study group in
      which they received plain 0.5% bupivacaine, 2.2 mL, and preservative-free
      morphine, 0.2 mg, diluted with normal saline to a total volume of 2.6 mL.
      Patients were monitored for up to 24 hours by staff blinded to group allocation.
      The level of pain was assessed by a visual analogue pain score and the time of
      first request for analgesia was noted. The results show the median pain-free
      period in the control group was nine hours (range, 2-24 hours), while it was 24
      hours (range, 16-24 hours) in the morphine group, a significant difference
      (P<0.05). No major complications were reported. Intrathecal morphine is a useful
      technique for giving post-operative pain relief, especially in the elderly, in
      whom many other techniques cannot be safely used.

PMID- 11847369
TI  - Improved Papanicolaou smear reporting through the use of automated data entry.
AB  - The implementation of an automated data entry and report generation system using
      an optical scanner and commercially available image processing program is
      described. This method could be easily adapted for use in other fields of medical
      research where the compilation of a large amount of repetitive data is involved,
      such as the filling in of questionnaires. Using an optical scanner for data entry
      improves the efficiency of report generation, thereby improving the turnaround
      time of reports. Reports are standardised and more easily understood by referring
      doctors. Data is also standardised and validated and is more amenable for quality
      assurance analysis, in the reminder service for patients, and gives a performance
      analysis of smear takers.

PMID- 11847370
TI  - Acute viral hepatitis in Hong Kong: a study of recent incidences.
AB  - Acute hepatitis patients admitted to a referral centre from January 1995 through
      December 1995 were studied to determine the seroprevalence of the hepatitis
      viruses and related risk factors. Of the 434 patients with acute viral hepatitis,
      the episodes due to hepatitis A, B, C, D, and non-A, non-B, non-C, (non-ABC) were
      214 (49.3%), 163 (37.6%), 7 (1.6%), 0 (0%), and 50 (11.5%), respectively. Acute
      hepatitis A and non-ABC hepatitis commonly occur in late spring and early summer
      and are probably related to the intake of shellfish and travel to endemic areas.
      Approximately 60% of cases of symptomatic hepatitis B infection were acute
      exacerbations of chronic infection. Sexual exposure was the single most important
      risk factor for acute hepatitis B infection. The rarity of acute hepatitis C and
      D might be related to the low rate of intravenous drug use in our locality.
      Hepatitis E virus probably contributed significantly to the cases of non-ABC
      hepatitis. Further studies are needed to establish the importance of various
      causative agents of acute hepatitis in Hong Kong.

PMID- 11847371
TI  - The use of endoscopy in liver diseases.
AB  - The use of fibre-optic endoscopy has greatly facilitated the management of some
      patients with chronic liver disease. Upper endoscopy plays a pivotal role in the
      diagnosis and management of oesophageal and gastric varices. With the use of
      reflectance septrophotometry, gastroduodenal mucosal haemoglobin concentration
      and oxygen saturation can be more precisely measured. Recently, it has been shown
      that acute gastroduodenitis is associated with a lower pre-treatment mucosal
      oxygen concentration in the antrum and the first part of the duodenum. Endoscopic
      ultrasound is increasingly being used to detect varices and in the staging of
      gastrointestinal tumours. Endoscopic retrograde cholangiopancreatography plays an
      important role in the diagnosis of recurrent pyogenic cholangitis and endoscopic
      sphincterotomy is a useful form of treatment. Laparoscopy, with the aid of
      ultrasound and biopsy is helpful in staging chronic liver disease, identifying
      focal lesions, and diagnosing peritoneal disease.

PMID- 11847372
TI  - Management of the complications of chronic liver disease.
AB  - The complications of severe chronic liver disease result from hepatocellular
      failure, portal hypertension, or a combination of both. Acute variceal
      haemorrhage can be effectively managed by drugs, endoscopic techniques, balloon
      tamponade, and surgery. The advent of the transjugular intrahepatic portosystemic
      stent-shunt has offered a new therapeutic option. Prevention of re-bleeding also
      depends on endoscopic therapy or surgery. Beta-blockers have been shown to be
      useful, not only in preventing re-bleeding, but also in primary prophylaxis.
      Spontaneous bacterial peritonitis has proved to be preventable by antibiotic
      prophylaxis. Massive ascites can be satisfactorily treated by repeated large
      volume paracentesis and albumin infusion. Hepatic encephalopathy responds to
      protein restriction and reduction of bowel ammonia production by classical and
      novel agents. Liver transplantation may be used for those with hepatorenal and
      hepatopulmonary syndromes and it is the ideal treatment of choice for all
      suitable patients with terminal chronic liver disease.

PMID- 11847373
TI  - The natural history of chronic hepatitis B infection.
AB  - Chronic hepatitis B infection is a global health problem that affects about 300
      million people. Of these, 75% are Chinese. Most Chinese who become chronic
      carriers, contract the virus during the perinatal period. The natural history of
      these chronic hepatitis B carriers includes an initial immune tolerance phase,
      followed by immune clearance and an inactive hepatitis B non-replicative phase
      with the development of cirrhosis that may be complicated by hepatocellular
      carcinoma. The classification of hepato-cellular carcinoma has recently been
      revised. Based on immunohistochemical studies, it has been found that patients
      with hepatocellular carcinoma and biliary markers have a poorer survival than
      patients with hepatocellular carcinoma but who have negative biliary markers.
      Sometimes, a fourth phase, a hepatitis B envelope-negative hepatitis B virus
      replicative phase, reflecting the emergence of a pre-core mutant strain, may
      follow. Our improved understanding of the natural history of chronic hepatitis B
      infection has led to more effective approaches towards the control of this viral
      infection and its sequelae. Most importantly, immunisation against hepatitis B
      virus in the perinatal setting has been shown to prevent chronic infection.

PMID- 11847374
TI  - Antiviral treatment for chronic hepatitis B.
AB  - An updated review of the antiviral agents currently available or under trial for
      the treatment of chronic hepatitis B is presented. There are two broad groups:
      (1) immunomodulators including interferon a (which also has a direct antiviral
      effect), thymosin a1 and Theradigm-HBV and (2) viral suppressors such as
      famciclovir and lamivudine. These agents are still in clinical trial worldwide,
      singly or in combination. Their long term efficacy in the treatment of hepatitis
      B remains to be evaluated.

PMID- 11847376
TI  - The changing epidemiology of recurrent pyogenic cholangitis.
AB  - Recurrent pyogenic cholangitis is prevalent in Hong Kong and East Asia. While the
      recent influx of Asian immigrants has resulted in more cases appearing in the
      West, over the past three decades, the overall incidence in East Asia has been in
      decline. The experience of the Queen Mary Hospital and other hospitals in the
      region has been confirmed by comprehensive surveys. The decline in incidence has
      been attributed to the improved economic situation and living standards with the
      associated westernisation of diet.

PMID- 11847375
TI  - Hypoglycaemia in hepatocellular carcinoma: a review.
AB  - Hypoglycaemia in patients with hepatocellular carcinoma is not a particularly
      important clinical entity, as it usually occurs during the terminal stage of the
      illness. As many as 13% of patients with hepatocellular carcinoma, however,
      develop hypoglycaemia early in the course of their illness. This latter group of
      patients show a distinct pattern in their clinical course and pathology.

PMID- 11847377
TI  - Germ cell tumours---local perspectives on a curable cancer.
AB  - Germ cell tumours are among the most curable solid cancers and have become a
      model for the multimodality approach in oncology. The experience of two
      institutions in Hong Kong involving 149 Chinese patients with testicular germ
      cell tumours and 10 patients with mediastinal germ cell tumours was reviewed and
      the overall results were found to be comparable with the global experience.
      Treatment strategies suitable for the local population are discussed. The earlier
      identification of patients with metastatic non-seminomatous germ cell tumours who
      have a poor prognosis, may be important in selecting patients for more intensive
      treatment such as high dose chemotherapy. With mediastinal germ cell tumours,
      survival is poorer and improved treatment results may only be possible with
      increased understanding of the biological abnormalities involved. An integrated
      multimodality approach to the diagnosis and treatment of this disease is vital to
      attain optimal management. For these reasons, it is recommended that all patients
      with germ cell tumours be referred to cancer centres where cross-specialty
      expertise and experience are available to manage these patients.

PMID- 11847378
TI  - Candida krusei infections and fluconazole therapy.
AB  - Candida species are by far the most common agents of mucosal fungal infection in
      man. While Candida albicans is the most notorious pathogen in this group, non
      albicans species such as Candida krusei are gradually emerging as pathogens of
      concern, especially in compromised hosts. It is thought that the wide use of the
      newer triazole drug, fluconazole, in HIV-infected individuals is contributing to
      this phenomenon. Studies in both humans and animals have now demonstrated
      prophylactic and therapeutic failure of fluconazole against C. krusei due to
      increasing resistance of the organism to this azole. Thus, the indiscriminate use
      of fluconazole, a drug with relatively minimal toxicity and excellent
      pharmacokinetics, may lead to the development of widespread resistance to this
      azole among Candida species.

PMID- 11847379
TI  - Gynaecological day surgery at a Hong Kong hospital.
AB  - A retrospective review was made of patients who underwent day surgery at a
      gynaecological day practice in Hong Kong from October 1993 to June 1994. The
      first three months of practice, which involved 326 patients, was analysed
      separately. During the initial period, 49.5% of patients who had gynaecological
      operations were managed as day patients. The rates for patients with prolonged
      hospital stay and cancelled operations were 15.6% and 3.0%, respectively. In the
      subsequent period, the incidence of prolonged hospital stay decreased to 7.4%,
      while the cancellation rate was similar, at 3.6%. Patients with a prolonged
      hospital stay were less likely to be Chinese, were more likely to have other
      medical problems, to be of American Society of Anesthesiologists Class II, and to
      have procedures that involved opening of the peritoneal cavity. Non-medical
      problems were an important reason for prolonged hospital stay (37.4%). The stay
      rate could be reduced by provision of a separate operating facility and by
      improved counselling and selection of patients.

PMID- 11847380
TI  - Previous private psychiatric treatment among public mental patients: a
      preliminary local survey.
AB  - There has been considerable concern over disturbances to the public-private
      equilibrium in local health care provision. We investigated the situation among
      mental patients. Only 11.5% of new patients presenting to a public general
      hospital psychiatric unit had consulted a private sector psychiatrist previously.
      Of these, 60% had moved to the public sector for financial reasons and the same
      proportion had had their last contact with private care within the previous three
      months. There were no dominant reasons for choosing the private sector initially.
      No particular privately practising psychiatrist's patients were more likely to
      seek public treatment subsequently. The results are analysed and the implications
      discussed.

PMID- 11847381
TI  - Endoscopic removal of leiomyoma of the colon.
AB  - Colonic leiomyoma is a rare condition. Smooth muscle tumours arising from the
      colon constitute only 3% of gastrointestinal leiomyomas. Complete endoscopic
      removal of the tumour is a problem because it is often submucosal in origin. We
      report a patient with a 5 mm leiomyoma of the colon that was successfully removed
      by conventional colonoscopic snare electrocauterisation, without complications.

PMID- 11847382
TI  - Plasmodium infection unmasked by corticosteroid therapy.
AB  - In the past four years, we have encountered three patients in whom malaria
      parasites were found incidentally in their blood when they were receiving
      corticosteroid therapy. Although there is little direct evidence that
      corticosteroid therapy can activate human malaria, animal studies have
      successfully demonstrated the recrudescence effect of immunosuppression on
      malaria infection.

PMID- 11847383
TI  - Cholestatic hepatitis: a rare hepatic manifestation of systemic lupus
      erythematosus.
AB  - Systemic lupus erythematosus is a multi-system inflammatory disease. The clinical
      manifestations are diverse. Hepatic manifestation is a rarely seen complication
      of systemic lupus erythematosus. We report a case of complication of systemic
      lupus erythematosus presenting as cholestatic hepatitis in a 56-year-old Chinese
      woman. The cholestatic hepatitis progressed as part of the lupus activity and
      responded to steroid therapy.

PMID- 11847384
TI  - Medical disorders in pregnancy.

PMID- 11847385
TI  - Nasopharyngeal carcinoma: presenting symptoms and duration before diagnosis.
AB  - This is a retrospective analysis of 4768 patients with undifferentiated or non
      keratinising carcinoma of the nasopharynx who were treated during 1 January 1976
      to 31 December 1985. The mean duration of symptoms before diagnosis was 8 months
      (range, 1-36 months for 95% of patients). A significant association between the
      duration of symptoms and the presenting stage was observed (P<0.001); 58% and 39%
      of stage I and stage V patients, respectively, reported as having had symptoms
      for less than 6 months. Of the later presenters (those having had symptoms for 6
      months or longer), 89% were given a full course of radical megavoltage
      radiotherapy, but 6% were too advanced for any irradiation attempt. Consequently,
      the 10-year actuarial disease-specific survival was significantly higher among
      the early presenters: 48% versus 42% (P<0.001). The importance of early detection
      is emphasised.

PMID- 11847386
TI  - Morbidity patterns of persons waiting for infirmary care in Hong Kong.
AB  - Ageing of the Hong Kong population is associated with an increased prevalence of
      physical and mental disability. For persons with severe disability, infirmary
      care is needed. In the present study, the morbidity pattern of persons waiting
      for infirmary service in Hong Kong was studied. Two hundred and four consecutive
      Central Infirmary Waiting List persons were included in the study. Clinical
      assessment was based on history review and physical examination. The commonest
      diagnoses giving rise to severe disability in this population, 89.2% of whom were
      elderly (aged greater-than-or-equal65 years), in descending order of prevalence
      were stroke (40.2%), dementia (27.0%), proximal femoral fracture (7.4%), and
      parkinsonism (5.9%); 67.5% of subjects were dependent physically. For cognitive
      function, 87.3% had a subnormal Abbreviated Mental Test score of less-than-or
      equal5. Approximately 80% had urinary incontinence and/or bowel incontinence. For
      the outcome of assessment, 93.6% needed infirmary care, while 6.4% did not. More
      adequate provision of infirmary beds, innovative medical, nursing, and social
      home-support programmes, and effective prevention and rehabilitation programmes
      for patients with these disabling diseases are urgently needed in Hong Kong.

PMID- 11847387
TI  - Fourteen-year experience of human leucocyte antigen typing in cases of disputed
      parentage in Hong Kong.
AB  - Seventy-seven cases of disputed parentage were studied using the human leucocyte
      antigen system over a 14-year period in Hong Kong. Of these, 30 (39.0%) related
      to the amendment or verification of birth registration details, 20 (26.0%) were
      for divorce or affiliation proceedings, and 19 (24.7%) were related to overseas
      resident visa applications. An exclusion of parentage of at least one of the
      alleged parents was shown in 23 (29.9%) cases; none of the cases related to
      overseas resident visa applications showed an exclusion. The study illustrates
      that human leucocyte antigen testing is a very powerful tool in the elucidation
      of disputed parentage in Hong Kong.

PMID- 11847388
TI  - The accuracy of Papanicolaou smear predictions: cytohistological correlation of
      283 cases.
AB  - The Papanicolaou smear is a highly effective screening test for the detection of
      cervical neoplastic changes. The success of the test has resulted in unrealistic
      expectations of the accuracy of the test by both referring medical practitioners
      and the public. However, as with any pathological test, it has irreducible false
      negative and positive rates. This report is a comparison between interpretations
      based on cytological and histological tests and was undertaken to estimate the
      sensitivity of the Papanicolaou test as practised in Hong Kong. The overall
      absolute concordance rate for the study was 51.2%. The concordance rates within
      one diagnostic category were 63.9% and 74.6% for low- and high-grade squamous
      intraepithelial lesions respectively. The overall sensitivity of the test was
      91.7% with a positive predictive value of 93.5%. Ten percent of the error rate
      was attributed to laboratory error; the remainder was attributed to sampling
      error and poor smear preparation. Forty-five percent of cases of atypical
      squamous cells of undetermined significance showed evidence of cervical
      intraepithelial neoplasia on subsequent biopsy. Follow-up biopsies of low-grade
      squamous intraepithelial lesions also showed as many lesions from cervical
      intraepithelial neoplasia grade I as from grades II and III. These findings
      suggest that colposcopies and biopsies should be performed as soon as possible
      rather than to repeat the smears in 3 to 6 months. The results of the study may
      provide guidelines for formulating follow-up recommendations.

PMID- 11847389
TI  - The accuracy of references in the Hong Kong Medical Journal.
AB  - We have reviewed the reference citations in volume 1 (1995) and volume 2 (1996)
      of the Hong Kong Medical Journal to determine their accuracy. One hundred
      references were randomly selected from each volume. After excluding references
      not from indexed journals, all citations were examined in detail by dividing them
      into six component elements and comparing them with the original. We found that
      61% of references in volume 1 and 51% of references in volume 2 contained
      inaccuracies, giving an overall error rate of 56%. Thirty-eight percent of
      references contained errors in one element, 16% contained errors in two elements,
      and 2% contained errors in three or more elements. The most common errors were
      those of the title or authors' names. The rate of citation errors in the Hong
      Kong Medical Journal is at the high end of the range compared with other medical
      journals. Contributors to this journal need to take more care in checking their
      references before publication.

PMID- 11847390
TI  - Impaired glucose tolerance in pregnancy.
AB  - Gestational diabetes mellitus is defined as carbohydrate intolerance of variable
      severity with onset or first recognition during pregnancy. It has been shown that
      the risk of adverse maternal, foetal, and neonatal outcomes in gestational
      diabetes mellitus is related to the degree of glucose intolerance and/or
      hyperglycaemia; gestational diabetes mellitus also has long-term sequelae for
      both the mother and the offspring. As gestational diabetes mellitus is rarely
      symptomatic, diagnosis of the condition relies on screening. The diagnostic
      criteria and the management of gestational diabetes mellitus are discussed and
      areas of controversy and recent advances highlighted.

PMID- 11847391
TI  - Thyroid disease in pregnancy.
AB  - It has long been known that there is a close relationship between pregnancy and
      the thyroid gland-iodine insufficiency, goitre development, and abnormal thyroid
      function are common during pregnancy. Autoimmune thyroid disease and
      thyrotoxicosis may also affect pregnant women, and their management requires the
      understanding of the interaction between the neuroendocrine and immune systems.
      In this article, the physiology of the thyroid gland during pregnancy and the
      interrelationship between pregnancy and autoimmune thyroid disease are discussed.

PMID- 11847392
TI  - Cardiac disease in pregnancy.
AB  - Cardiac disease is an uncommon but potentially serious medical complication of
      pregnancy. It is an important cause of preventable maternal and perinatal
      mortality and morbidity. A multidisciplinary approach involving close liaison and
      collaboration between the obstetrician, cardiologist, anaesthetist,
      neonatologist, paediatric cardiologist and, if appropriate, the cardiothoracic
      surgeon, is essential to achieve optimal care in such pregnancies. The principles
      of management that ensure a good pregnancy outcome include pre-pregnancy
      counselling, recognition of risk factors, early diagnosis, close obstetric and
      medical surveillance, anticipation and prompt identification and treatment of
      complications, the appropriate use of drugs, surgical intervention, and timely
      delivery of the baby.

PMID- 11847393
TI  - Neurological disorders in pregnancy.
AB  - Pregnant women can present with a wide variety of neurological conditions.
      Patient data from 1 January 1985 through 31 December 1994 for all deliveries at
      the Tsan Yuk and Queen Mary hospitals were reviewed to determine the local
      frequency of various neurological conditions during pregnancy. Conditions
      including epilepsy, eclampsia, facial nerve palsy, pituitary tumour,
      cerebrovascular disorders, myasthenia gravis, multiple sclerosis, and non
      pituitary intracranial tumours were encountered, in descending order of
      frequency. The limitations of this retrospective analysis are acknowledged. This
      paper reviews the current concepts of these conditions and outlines appropriate
      management.

PMID- 11847394
TI  - Cardiovascular effects of sleep-related breathing disorder.
AB  - Sleep-related breathing disorder is a prevalent medical condition that remains
      underdiagnosed in the community. This disorder has social, behavioural and
      neuropsychological impact, deleterious haemodynamic effects during sleep, and is
      associated with increased cardiovascular morbidity. This review aims to describe
      the current evidence for the association of sleep-related breathing disorder with
      hypertension, ischaemic heart disease, heart failure, and stroke, based on the
      knowledge of its haemodynamic effects during sleep.

PMID- 11847395
TI  - Obstructive sleep apnoea syndrome in children.
AB  - Obstructive sleep apnoea syndrome in children is characterised by recurrent
      complete and/or partial upper airway obstruction during sleep. Owing to the
      limited number of studies, the exact prevalence rate has yet to be determined,
      but an estimate as high as 1% to 3% has been suggested. Recent studies have shown
      that obstructive sleep apnoea syndrome in children is different from that in
      adults in its distinct clinical presentation, diagnostic criteria and treatment.
      Polysomnography is now recommended as the standard investigation for confirming
      the diagnosis. The majority of patients may benefit from removal of the enlarged
      tonsils and adenoids. Although nasal continuous positive airway pressure therapy
      has been the mainstay of treatment for adults with obstructive sleep apnoea
      syndrome, experience of its therapeutic effect on children is limited; recent
      reports are encouraging. Further efforts are needed in advancing both the
      clinical management of and research into this disorder.

PMID- 11847396
TI  - Preventing avoidable death: the case of cervical cancer in Hong Kong.
AB  - Cervical cancer remains an important cause of avoidable morbidity and mortality
      in Hong Kong. This paper briefly reviews the epidemiology of cervical cancer and
      explores the evidence on the effectiveness of screening. The essential components
      of a successful cervical cancer screening programme, based on international
      experience, are discussed. The present situation in Hong Kong is then examined
      and the options outlined for the way ahead.

PMID- 11847397
TI  - The variable presentation and early recognition of anorexia nervosa in Hong Kong.
AB  - One of the western diagnostic criteria for anorexia nervosa is a 'morbid or
      intense fear of fatness', which is absent in some Chinese anorexic patients in
      Hong Kong. As a result, patients often visit non-psychiatric doctors and have
      extensive investigations performed. By the time they are referred to
      psychiatrists, some may already have reached an advanced stage of illness. In
      this report of two patients with anorexia nervosa, we attempt to illustrate the
      variable presentation of anorexic patients in Hong Kong, and to alert health
      professionals to the early recognition and treatment of this potentially lethal
      disorder.

PMID- 11847398
TI  - Hereditary angioedema in a Chinese family.
AB  - Hereditary angioedema is characterised by recurrent episodes of peri-orbital and
      peri-oral swelling which can cause an upper airway obstruction, abdominal pain,
      vomiting, diarrhoea, and even hypotensive collapse. This potentially fatal
      condition is frequently misdiagnosed; its early recognition and appropriate
      treatment are thus important. We report a familial cluster of hereditary
      angioedema in a Chinese family and describe the clinical course of two patients.

PMID- 11847399
TI  - Creutzfeldt-Jakob disease in Hong Kong.
AB  - Two elderly patients presented with rapidly progressive dementia and their
      electroencephalograms showed periodic discharges. Creutzfeldt-Jakob disease was
      pathologically confirmed in one of the patients. Striking clinical features and
      characteristic electroencephalograms should prompt the clinical diagnosis in most
      patients.

PMID- 11847400
TI  - A woman with persistent vaginal bleeding after suction evacuation of the uterus.

PMID- 11847401
TI  - Management of acute coronary syndromes with emphasis on new information for the
      treatment of ST-segment elevation acute myocardial infarction.

PMID- 11847402
TI  - Present and potential future paradigms for the treatment of ST-segment elevation
      acute myocardial infarction.

PMID- 11847403
TI  - The GUSTO-V clinical trial.

PMID- 11847404
TI  - Managing unstable angina in high-risk patients.

PMID- 11847405
TI  - Safety of plasma-based sterilization: surface modifications of polymeric medical
      devices induced by Sterrad and Plazlyte processes.
AB  - Plasma-based sterilization is a promising alternative to the use of pure ethylene
      oxide (EO), for low-temperature clinical sterilization of medical instruments and
      devices. However, few studies have been published that evaluate its safety in
      terms of possible damage to materials, particularly polymers. The objective of
      this work was to evaluate polymer surface modifications induced by commercial
      plasma-based sterilizers, in comparison with pure EO: Samples from 5 polymer
      based devices were subjected to 1, 5, and 10 sterilization cycles by Sterrad-100,
      Plazlyte, and pure EO. Surface analysis was carried out by X-ray photoelectron
      spectroscopy (XPS), dynamic contact angle measurements (DCA), and scanning
      electron microscopy (SEM). Surface oxidation and wettability changes were
      observed on all samples sterilized by plasma-based techniques, the degree of
      modifications depending on the sterilizer (Sterrad, Plazlyte) and the type of
      polymer. Drastic changes of surface appearance were also observed by SEM on PVC
      samples sterilized by Plazlyte and by pure EO. Possible repercussions on safety
      are discussed.

PMID- 11847406
TI  - Natural coral exoskeleton as a bone graft substitute: a review.
AB  - Natural coral graft substitutes are derived from the exoskeleton of marine
      madreporic corals. Researchers first started evaluating corals as potential bone
      graft substitutes in the early 1970s in animals and in 1979 in humans. The
      structure of the commonly used coral, Porites, is similar to that of cancellous
      bone and its initial mechanical properties resemble those of bone. The
      exoskeleton of these high content calcium carbonate scaffolds has since been
      shown to be biocompatible, osteoconductive, and biodegradable at variable rates
      depending on the exoskeleton porosity, the implantation site and the species.
      Although not osteoinductive or osteogenic, coral grafts act as an adequate
      carrier for growth factors and allow cell attachment, growth, spreading and
      differentiation. When applied appropriately and when selected to match the
      resorption rate with the bone formation rate of the implantation site, natural
      coral exoskeletons have been found to be impressive bone graft substitutes. The
      purpose of this article is to review and summarize all the pertinent work that
      has been published on natural coral as a bone graft including in vitro, animal
      and clinical human studies. Preliminary report of our own experiments as well as
      our recommendations on the use of coral are also included.

PMID- 11847407
TI  - Characteristics of porous nickel-titanium alloys for medical applications.
AB  - We investigate the behavior of NiTi porous alloys, possessing the property of
      shape memory, by using different characterization methods XPS, Auger, DSC and
      SEM. The study mainly focuses on the determination of porosity, surface
      characteristics and the phase transformation. In the case of porous material the
      biomechanical compatibility is closely related to the internal structure and
      porosity distribution. To describe appropriately the influence of the properties
      of NiTi on the memory shape, two types of materials provided by different sources
      has been analyzed. Despite the fact that both materials present different pores
      size, they exhibit an open and interconnected porosity. Our measurements show
      that the temperature of the inception of the martensite-austenite phase
      transition occurs at 60 degrees C, which is by 20 degrees C greater than the body
      temperature. Moreover, we show that the surface characteristics can be greatly
      influenced by heat treatment. Furthermore, we observe that the R-phase occurs
      only for one of the used materials after its heat treatment. The correlation
      between the composition and the other characteristics measured has been found.

PMID- 11847408
TI  - Quantitative comparison of three different types of anterior cruciate ligament
      reconstruction methods: laxity and 3-D kinematic measurements.
AB  - In this project, we compared knee laxity and 3-D knee kinematics after ACL
      reconstruction on cadaver knees using (1) bone-patellar tendon-bone two-tunnel;
      (2) synthetic ligament two-tunnel; and (3) synthetic ligament "over-the-top"
      technique. We used a computer assisted system, based on the acquisition of the
      knee's movement with magnetic sensors (Polhemus, Vermont, USA). The use of
      personalised three-dimensional (3D) models of the bones enabled us to ensure a
      reproducible measurement of three-dimensional kinematic and laxity parameters.
      Our results showed that even when knee laxity was restored to normal, 3D
      kinematic measurements revealed that the reconstructions tended to under or over
      constrain the knee's movement. This study shows that 3D kinematics is a
      complementary measurement that can be useful to get a better comprehension of the
      knee's function after ligament reconstruction.

PMID- 11847409
TI  - Anterior cruciate ligament reconstruction using an alloplastic ligament of
      polyethylene terephthalate (PET -- Trevira -- hochfest). Follow-up study.
AB  - Between April 1989 and July 1996, 217 anterior cruciate ligament reconstructions
      using a synthetic ligament of polyethylene terephthalate (PET Trevira-- hochfest)
      were performed. 160 (74%) cases have been followed-up with a mean time of 4.8
      years (1.0-8.3) and evaluated by the IKDC standard knee ligament evaluation form.
      Altogether 88% excellent and good results were found. The best outcomes involved
      isolated ACL tears and reconstruction within a few month. The amount and
      intensity of lasting symptoms depended mostly on osteoarthrotic changes (chondral
      and meniscal lesions) and correlated with the interval between injury and
      reconstruction. All findings are presented in detail and critically discussed.

PMID- 11847410
TI  - Surface, corrosion and biocompatibility aspects of Nitinol as an implant
      material.
AB  - The present review surveys studies on physical-chemical properties and biological
      response of living tissues to NiTi (Nitinol) carried out recently, aiming at an
      understanding of the place of this material among the implant alloys in use.
      Advantages of shape memory and superelasticity are analyzed in respect to
      functionality of implants in the body. Various approaches to surface treatment,
      sterilization procedures, and resulting surface conditions are analyzed. A review
      of corrosion studies conducted both on wrought and as-cast alloys using
      potentiodynamic and potentiostatic techniques in various corrosive media and in
      actual body fluids is also given. The parameters of localized and galvanic
      corrosion are presented. The corrosion behavior is analyzed with respect to alloy
      composition, phase state, surface treatment, and strain and compared to that of
      conventional implant alloys. Biocompatibility of porous Nitinol, Ni release and
      its effect on living cells are analyzed based on understanding of the surface
      conditions and corrosion behavior. Additionally, the paper offers a brief
      overview of the comparative toxicity of metals, components of commonly used
      medical alloys, indicating that the biocompatibility profile of Nitinol is
      conducive to present in vivo applications.

PMID- 11847411
TI  - The role of intravenous volume expansion in moderate pre-eclampsia.
AB  - We examined the hemodynamic and hemorheological effects of intravenous volume
      expansion in women with pre-eclampsia. 20 untreated women with moderate pre
      eclampsia were randomized to receive a 500 ml infusion over 4 h of either
      hydroxyethylstarch (HAES steril 10%, HES) or NaCl 0.9% solution. After completion
      of the infusion trial all patients received oral antihypertensive drugs, bed rest
      and free sodium and water intake. The hemodynamic responses were measured by
      impedance cardiography. Hemorheological parameters and blood pressure were
      measured before and after (24 h later) infusion. The HES infusion but not NaCl
      leads to a significant reduction of hematocrit and erythrocyte aggregation. In
      addition to that there was a nonsignificant increase of the cardiac index in the
      HES-group but no changes in the heart rate. Intravenous volume expansion in women
      with pre-eclampsia with a long acting colloid like hydroxyethylstarch is
      associated with a significant influence on the flow properties (hematocrit and
      erythrocyte aggregation) of blood.

PMID- 11847412
TI  - Multivariate analysis of relationships between insulin sensitivity and blood
      rheology: is plasma viscosity a marker of insulin resistance?
AB  - We previously reported in populations exhibiting all the spectrum of insulin
      sensitivity (SI) values correlations between SI and blood viscosity eta
      suggesting that high eta is an additional symptom of the insulin resistance
      syndrome. However, due to the elevation of insulinemia (I) which is usually
      associated with insulin resistance it remained to determine whether this
      relationship was explained by SI or I. We analyzed SI with the minimal model
      procedure in 108 nondiabetic subjects and analyzed correlations of SI with blood
      rheology (eta, RBC aggregation and rigidity). Across quartiles of SI (defined
      after log transformation since distribution of SI was not normal), hematocrit and
      red cell rigidity remained stable, while aggregability and plasma viscosity
      (etap) increased in the lowest quartile. SI was correlated to only two
      rheological parameters: etap (r= -0.280, p=0.005) and Myrenne index M1 (r= 
      0.219, p=0.044). Among SI, I, age and BMI multivariate analysis selected only BMI
      as a determinant of either whole blood viscosity (etawb: r= -0.301, p=0.004) and
      RBC disaggregation threshold (gammaD: r= -0.331, p=0.013), only I as determinant
      of M1 (r=0.254, p=0.03), and a combination of BMI (p=0.009) and SI (p=0.007) for
      etap. Although age and obesity are factors of hyperviscosity, the hemorheological
      disturbances found in insulin resistance are not fully statistically "explained"
      by those two factors. While hyperaggregability (measured with M1) is rather
      related to hyperinsulinism, etap is influenced by SI and should be further
      investigated as a simple marker for the follow up of insulin-resistant states.

PMID- 11847413
TI  - Aggregation and sedimentation of mixtures of erythrocytes with different
      properties.
AB  - The rouleau formation of erythrocytes and the erythrocyte sedimentation were
      examined for mixture of different kinds of the cells suspended in isotonic
      phosphate-buffered saline containing 1 or 2 g/dl dextran T-70 (MW = 70,400) and 4
      g/dl albumin, using a low shear rheoscope and the Westergren method,
      respectively. The deformability of cells was decreased by treating with diamide,
      diazene-dicarboxylic acid bis[N,N-dimethylamide], and the sialic acid content of
      cells, i.e., the surface negative charge, was reduced by treating with
      neuraminidase. (1) The rate of rouleau formation was decreased in cells with
      decreased deformability, while it was increased in cells with reduced sialic acid
      content. The rate changed in proportion to the ratio of the modified cells to
      normal cells. (2) The erythrocyte sedimentation was also decreased in cells with
      decreased deformability, while it was increased in cells with reduced sialic acid
      content. Furthermore, the erythrocyte sedimentation changed almost proportionally
      to the ratio of the modified cells to normal cells. (3) When normal deformable
      cells were mixed with cells with decreased deformability, the deformable cells
      seemed to settle faster than the less deformable cells, though the difference was
      not significant. (4) When normal cells were mixed with cells with reduced sialic
      acid content, the cells with less sialic acid settled significantly faster than
      those with more sialic acid. The present experiment may conclude that erythrocyte
      aggregation is induced preferentially among more deformable cells and/or among
      less negatively charged cells with weaker electrostatic repulsive force, and then
      the formed aggregates settle faster.

PMID- 11847414
TI  - Spontaneous echo-contrast as an in vivo indicator of rheological imbalance in
      dilatative cardiomyopathy.
AB  - The aim of this study was to evaluate coagulative and hemorheologic assessment in
      patients with dilatative cardiomyopathy with or without spontaneous echo contrast
      (SEC). We studied 45 patients, 35 males and 10 females (mean age 72.1 +/- 9.2).
      We measured whole blood viscosity, plasmatic fibrinogen, prothrombin time (PT),
      activated partial thromboplastin time (aPTT), D-dimer and red cell morphology
      with Zipursky-Forconi method. Transthoracic and transesophageal echocardiography
      was performed in all patients to evaluate the presence of SEC in left atrium. We
      divided all the patients into two groups: the 1st group of 20 patients with SEC
      and Atrial Fibrillation (AF) in 80% of cases, and the 2nd group of 25 patients
      without SEC and AF in 31%. Our results show that in patients with SEC there is a
      statistically significant increase of whole blood viscosity and plasma fibrinogen
      in comparison with patients without SEC. Red cell morphology in all patients
      demonstrates a reversed EMI. D-Dimer, was out of the normal range in about 1/3 of
      the patients in both groups. An analysis of our results points out that in
      patients with SEC and AF, with a major risk factor for cardioembolic stroke, we
      have alterations of hemorheologic assessment with an increase of whole blood
      viscosity and fibrinogen that seems to be caused by an increase of red cells
      aggregability favoured by fibrinogen. Our conclusions are that SEC in patients
      with dilatative cardiomyopathy and AF is an important in vivo indicator of
      hemorheologic imbalance and an important marker for cardioembolic risk stroke
      evaluation.

PMID- 11847415
TI  - Beta-estradiol effect on erythrocyte aggregation--a controlled in vitro study.
AB  - The purpose of this in vitro study was to assess the effect of 17beta-estradiol
      on hemorheologic parameters, namely on erythrocyte aggregation and deformability
      and membrane fluidity. Blood samples from 65 women (aged 57 +/- 4 years)
      undergoing postmenopausal hormone replacement therapy were obtained and were
      incubated for 5 min in absence and presence of 17beta-estradiol 10(-5) M. The
      measured parameters were the erythrocyte aggregation (EAI) and deformability
      (EI), the acetylcholinesterase activity (AChE), the plasma pH and osmolality and
      the erythrocyte membrane fluidity assessed by fluorescence polarization with two
      probes 1,6-diphenyl-1,3,5-hexatriene (DPH) and (1-(4-(trimethylamino)-phenyl)-6
      phenyl-1,3,5-hexatriene (TMA-DPH). Data analysis was performed using t-Student
      and Pearson correlation analysis. A statistically significant decrease of the EAI
      (15.8 +/- 3.02 vs 13.45 +/- 2.3; p<0.001) and an increase of the EI (51.39 +/-
      5.64 vs 52.06 +/- 5.36; p<0.01) at shear stress of 30 Pa in presence of 17beta
      estradiol 10(-5) M was obtained. There was a decrease in membrane fluidity in 45
      blood samples (DPH) and in the other 20 an increase, when beta-estradiol 10(-5) M
      was present. In vitro beta-estradiol 10(-5) M decreased erythrocyte aggregation
      in blood samples of postmenopausal women undergoing hormone therapy, which could
      prevent high blood viscosity and, consequently, cardiovascular events.

PMID- 11847416
TI  - Effect of ethanol on hemorheology in patients with ischemic cerebrovascular
      disease and elderly healthy men.
AB  - Changes in hemorheological parameters were studied in patients with ischemic
      cerebrovascular disease and elderly healthy men who ingested ethanol at 0.5 and 1
      g/kg body weight. Following ingestion of 1 g/kg, but not 0.5 g/kg of ethanol,
      there were significant changes in hemorheologic factors. Whole blood viscosity
      (WBV, shear rate: 18.8, 37.5, 75, 150, 350 sec(-1)) and blood viscosity corrected
      for hematocrit (BVC) were increased. WBV and BVC at high shear rate were
      increased and red blood cell deformability impaired in patients with ischemic
      cerebrovascular disease, while those factors were not significantly changed in
      healthy men. It is considered that ethanol ingestion could has bad influences for
      the microcirculation in patients with ischemic cerebrovascular disease.

PMID- 11847417
TI  - The influence of low-power laser energy on red blood cell metabolism and
      deformability.
AB  - The aim of this study was to test the hypothesis that exposure of red blood cells
      (RBC) to low-power laser energy can modulate their metabolism and deformability.
      The effects of exposure to a He-Ne (lambda=632.8 nm), GaAlAs (lambda=780 nm) and
      GaAs (lambda=904 nm) lasers have been examined. Red cells diluted to a hematocrit
      of 45% were incubated in a humidified atmosphere of 95% air and 5% CO(2) at 37
      degrees C, and exposed to three different laser beams held 5 cm from the target
      area to yield a spot surface area of 2 cm(2). Three red cell suspensions
      belonging to the experimental groups were treated with each laser beam by 5, 15
      and 30 minutes, respectively. The temperature was constant during the exposure's
      time. Three control suspensions of RBC were kept for the same time as sham
      irradiated groups. The erythrocyte elongation index (EEI) was evaluated using a
      Rheodyn SSD (Myrene, Roetgen, Germany). The enzyme activities of glucose-6
      phosphate dehydrogenase (G-6-PD), glutathione peroxidase (GSH-Px) and glutathione
      reductase (GR) were assayed in each sample spectrophotometrically. Adenosine
      triphosphate (ATP) and diphosphoglicerate (2,3-DPG) levels were also assessed. No
      statistical differences were observed in the erythrocyte elongation index at
      shear stresses of 0.30, 0.60, 1.20, 3.00, 6.00, 12.00, 30.00 and 60.00 Pa after
      being irradiated for 5 and 15 minutes as compared to not irradiated ones. At
      30.00 and 60.00 Pa a decrease (p<0.03 and p<0.05, respectively) in EEI has been
      observed after 30 min exposure to all three wavelengths of laser light when
      compared to the control. The antioxidant enzyme activities showed no significant
      changes following 5, 15 and 30 min of irradiation by all three laser wavelengths
      laser tested. Similarly, erythrocyte organic phosphate levels (ATP and 2,3-DPG)
      showed no significant changes following treatment by laser radiation. This study
      revealed that the low-power laser at 632.8, 780 and 904 nm wavelengths have
      little biological effects on red blood cells in vitro.

PMID- 11847418
TI  - Effects of acetylcholine and spermineNONOate on erythrocyte hemorheologic and
      oxygen carrying properties.
AB  - PURPOSE OF THE STUDY: To determine the effects of acetylcholine and
      spermineNONOate--a NO donor--on RBC membrane and oxygen carrying properties.
      MATERIAL AND METHODS: Aliquots of venous blood from eleven healthy subjects were
      incubated with ACh 10(-3) M, ACh 10(-5) M, spermineNONOate 10(-5) M and
      spermineNONOate 10(-4) M. The following parameters were determined: erythrocyte
      aggregation and deformability, hematocrit, plasma pH, osmolality, K(+), Na(+),
      Ca(2+) concentrations, hemoglobin, oxyhemoglobin, carboxyhemoglobin and
      methemoglobin concentrations, oxygen saturation of hemoglobin, oxygen and carbon
      dioxide partial pressures and p50. RESULTS: In presence of ACh there is an
      increase of erythrocyte deformability, decrease of erythrocyte aggregation,
      plasma pH, K(+) and Na(+) concentration, increase of Ca(2+) concentration and
      p50. In presence of spermineNONOate there is an increase of erythrocyte
      deformability, plasma pH, decrease of Na(+) and Ca(2+) concentration, increase of
      metHb concentration and decrease of p50. CONCLUSION: Acetylcholine and
      spermineNONOate are able to induce changes on RBC membrane and oxygen carrying
      properties.

PMID- 11847419
TI  - The concomitant appearance of aggregated erythrocytes, leukocytes and platelets
      in the peripheral blood of patients with risk factors for atherothrombosis.
AB  - Risk factors for atherothrombosis including increased leukocyte count,
      hyperlipidemia, diabetes mellitus, hypertension as well as smoldering
      inflammation and hyperfibrinogenemia might affect the aggregability of peripheral
      blood erythrocytes, leukocytes as well as platelets. We have used a simple slide
      test and image analysis to reveal the presence of these aggregabilities obtained
      in one single drop of peripheral venous citrated blood in 48 individuals with
      risk factors for atherothrombosis. A significant correlation was noted between
      the state of adhesiveness/aggregation of all the above mentioned three cellular
      elements and the concentrations of total and LDL cholesterol. The correlation
      with triglycerides concentrations was more modest. A significant reduction of
      adhesiveness/aggregation was noted in 18 individuals following an intervention to
      reduce the concentration of cholesterol and triglycerides. This reduction might
      have a favorable hemorheologic effect. Our results are significant in that they
      show that it is possible to detect the above mentioned changes in whole blood,
      following a single step and minimal manipulations, at real time and low cost.

PMID- 11847420
TI  - Phage antibodies from combinatorial library neutralize vaccinia virus.
AB  - The library of human scFv antibodies displayed on the surface of bacteriophages
      was panned against Vaccinia virus (VACV), strain Elstree. 75% binding with
      Vaccinia virus. 5 clones were characterized for their binding with VACV and their
      ability to neutralize VACV in plaque reduction neutralization test (PRNT).
      Antibodies from the clones were obtained as soluble individual molecules and
      their binding activities were confirmed in ELISA.

PMID- 11847421
TI  - Generation of monoclonal antibody CIBCgp185 against C-erbB-2 oncoprotein and its
      clinical evaluation.
AB  - The C-erbB-2 proto-oncogene encodes the production of a cell surface receptor
      protein, with tyrosine kinase activity. Over expression of this gene either due
      to gene amplification and/or increased transcription has been observed and has
      been correlated with poor prognosis in patients with Breast (10-33%) and ovarian
      (20-33%) cancers. The very low levels of expression of C-erbB-2 by normal tissues
      makes this receptor a potential target for diagnosis and therapy with Monoclonal
      antibodies raised against its extracellular domain. One such monoclonal antibody
      designated as CIBCgp185 of IgG2a isotype has been generated in our laboratory
      using BT474 breast carcinoma cell line as immunogen. This monoclonal antibody
      immunoprecipitated a 185 KD glycoprotein. The specificity of this antibody was
      confirmed by the formation of a single discrete band and positive reaction with
      BT474 antigen in Western blot and Dot blot respectively. Flowcytometric analysis
      performed using various cancer cell lines revealed that this Monoclonal antibody
      exhibited high binding affinity with BT474 and SKBR3 cells whichoverexpresses C
      erbB-2. By immunoperoxidase test, this antibody stained specifically the tumor
      cell membrane in frozen tissue sections of breast and ovarian tumors indicating
      overexpression of the C-erbB-2 product. All these results well correlated with
      those obtained using a control antibody ICR12, an anti-C-erbB-2 antibody. These
      studies clearly indicate that Monoclonal antibody CIBCgp185 might prove useful to
      identify tumors with over expression of C-erbB-2 which are often associated with
      poor prognosis and early recurrence.

PMID- 11847422
TI  - Pertinence of kappa and lambda recombinant antibodies directed against thyroid
      peroxidase in thyroid autoimmune disease.
AB  - Forty-one single-chain variable region fragments (scFvs) directed against thyroid
      peroxidase (TPO) were obtained by phage display libraries constructed from
      thyroid-infiltrating B cells of Graves' disease patients. Among these scFvs,
      24.4% used a Vkappa light chain whereas 75.6% shows a light chain of Vlamda
      origin. Study of light chain gene usage in the TPO antibody repertoire
      demonstrated a dominance of the Vkappa 1-39 and Vlambda 1-51 genes. Thyroid
      peroxidase probing of overlapping peptides covering the amino acid sequences of
      anti-TPO T2/kappa and T13/lambda variable regions demonstrated a more restricted
      antigen recognition on T13/lambda than on T2/kappa. These two recombinant
      antibodies, expressed as whole IgG1 in the baculovirus/insect cell system,
      inhibited the binding to TPO of serum TPO autoantibodies whatever the light
      chain. Our study indicates that lambda as well as kappa light chain usage are
      found in the TPO antibody repertoire of thyroid-infiltrating B cells and are
      pertinent in the pathogenesis of autoimmune thyroid disease.

PMID- 11847423
TI  - Natural anti-FcepsilonRIalpha autoantibodies isolated from healthy donors and
      chronic idiopathic urticaria patients reveal a restricted repertoire and
      autoreactivity on human basophils.
AB  - The role of autoantibodies against the alpha-subunit of the human high-affinity
      IgE receptor (FcepsilonRIalpha) in the pathogenesis of chronic idiopathic
      urticaria (CIU) is controversial. We have shown that these antibodies are
      widespread, apparently non-pathogenic and belong to the natural antibody
      repertoire. To clarify this controversy, we constructed antibody libraries from
      both healthy donors and CIU patients with active disease. Here we describe the
      first three high affinity IgM anti-FcepsilonRIalphaautoantibodies isolated from
      normal and urticaria libraries. Sequence analysis revealed germline VH in both
      cases paired with a slightly mutated VL, thus supporting their classification as
      natural antibodies. Strikingly, one major IgM clone was present in both CIU
      patients and normal donors. The anti-FcepsilonRIalpha autoantibodies recognize
      FcepsilonRIalpha on cells, but are non-anaphylactogenic on blood basophils,
      except when IgE is removed from the receptor. Based on their functional
      activities we propose a concept of "conditional autoimmunity" where natural anti
      FcepsilonRIalphaautoantibodies can become pathogenic dependent on the state of
      occupancy of the FcepsilonRIalpha by its natural ligand IgE.

PMID- 11847424
TI  - Engineered antibodies take center stage.
AB  - The start of the post-genomic era provides a useful juncture for reflection on
      the state of antibody engineering, which will be a critical technology for
      relating function and pathology to genomic sequence in biology and medicine. The
      phenomenal progress in deciphering the human genome has given significant impetus
      to the application of engineered antibodies in proteomics. Thus, advances in
      phage display antibody libraries can now help to define novel gene function and
      the measurement of abnormal protein expression in pathological states.
      Furthermore, intrabody and antibody engineering provide vehicles for the
      development of molecular medicines of the future. In addition to these new
      directions, antibody engineering has begun to show concrete success in its long
      term efforts to develop targeted immunotherapies for cancer and other diseases.
      The cornerstones of clinical development are the detailed academic clinical
      trials that continue to push the boundaries of engineered antibodies into the
      real world. The field displays a healthy impatience for practical results, as
      research accelerates with concerted efforts to transfer preclinical insights into
      clinical trials. Growing private and governmental expenditures will lead to the
      rapid expansion of life-saving immunotherapeutic agents. The present review
      developed from our effort to report on the 11th Annual International Conference
      on Antibody Engineering (3-6 December 2000). This annual meeting is a forum for
      discussions on the latest advances in antibody engineering groups from around the
      world, and now includes the broader agenda of engineering in molecular
      immunology. In bringing scientists together to exchange ideas at this open forum,
      new collaborations and the threads of new discoveries are woven. For example,
      Professors Gerhard Wagner (Harvard Medical School), Dennis Burton (Scripps
      Research Institute), and Peter Hudson (CSIRO, Melbourne, Australia) gave exciting
      insights on structural immunobiology that had implications across many
      disciplines. The growth in antibody engineering was highlighted by the attendance
      of some 600 participants at the meeting, doubling that of the 1999 meeting.
      Dramatic clinical acceptance of monoclonal antibodies during the past two years
      has fostered this growth, with sales in 2000 of 1.8 billion dollars and
      projections for 2001 of 3 billion dollars. However, economic measures cannot
      begin to convey the medical revolution that is being effected by these first
      humanized and chimerized monoclonal antibodies. At this juncture, the 10
      monoclonal antibody therapeutics in clinical use are of murine origin, of which 3
      are entirely murine (OKT3, Mylotarg, 90Y-labeled Bexxar), 4 have been chimerized
      (human constant domains replacing murine) (ReoPro, Rituxan and its 131I-labeled
      analogue (Zevalin), Simulect, Remicade) and 3 were chimerized and humanized
      (human residues being substituted for at least some mouse-specific framework
      residues in VH and VL) (Zenapax, Herceptin, Synagis). Fully humanized anti-CD52
      (CAMPATH-1H) has also been approved by the FDA for the treatment of B-cell
      chronic lymphocytic leukemia and should become available in late 2001.
      Humanization was initially developed by Dr. Greg Winter at the MRC Laboratory of
      Molecular Biology (Cambridge, UK), who presented the meeting's keynote address,
      "Antibodies as a Paradigm for Molecular Evolution". His pioneering work in
      antibody phage display libraries has been reformulated into a daring approach to
      develop truly novel proteins with genetically paired structural elements. He
      described studies in combinatorial protein engineering with enormous implications
      for both industrial and therapeutic applications of macromolecules.

PMID- 11847425
TI  - Enzyme immunoassay of human epidermal growth factor receptor (hEGFR).
AB  - Overexpession of EGFR has been reported in a variety of human cancers and serves
      as a target for diagnosis and therapy. In the case of breast cancer, about 48%
      EGFR and have poor clinical prognosis. Besides the prognostic factors like tumor
      size, nodal status, histological grade etc., which are significant in the
      management of breast cancer, EGFR level might also serve as an additional
      parameter. Immunocytochemical assay has been extensively used to study the
      expression of EGFR in various cancers. We have generated a panel of monoclonal
      antibodies against human EGFR with a view to evaluate their application for the
      diagnosis and therapy of these cancers. In the present study, an EIA has been
      developed using 2 monoclonal antibodies against hEGFR designated as CIBCNSH3 as
      the capture antibody and CIBCRGC1 as the detector antibody. EGFR isolated from
      MDA MB 468, a human breast carcinoma cell line, with high expression of EGFR and
      purified by conA affinity chromatography and HPLC has been used to develop the
      EIA procedure. Sera samples of 150 healthy women donors, of 300 breast cancer
      patients with different histological types of malignancies and of various other
      types of cancers have been analyzed. The control women had a range for serum EGFR
      level of 7-162 fmol/ml, whereas the 300 breast cancer patients studied had a
      range of 126-1587 fmol/ml with a cut off value of 180 fmol/ml. It is interesting
      to note that 67.5% of breast cancer patients had elevated levels of circulating
      EGFR. These results might suggest that serum EGFR level can be used as prognostic
      marker for breast cancer. The serum EGFR level will be compared with disease free
      interval and patient survival.

PMID- 11847426
TI  - A novel expression vector for production of epitope-tagged recombinant Fab
      fragments in bacteria.
AB  - Labeling of recombinant Fab molecules is an important yet cumbersome and time
      consuming procedure that is needed in many immunological experimental designs.
      This work describes the development of a novel expression vector fusing to the
      carboxyterminal of the Fab heavy chain fragments a tag peptide (FLAG) that is
      consistently recognized by a mouse monoclonal antibody. The presence of the FLAG
      peptide does not alter the binding characteristics of the unmodified Fab
      molecule, as demonstrated by relative affinity determinations and competition
      experiments. This new method is suitable for extensive utilization in
      immunological experimental work using recombinant Fabs.

PMID- 11847427
TI  - Microarrays: applications in neuroscience to disease, development, and repair.

PMID- 11847428
TI  - Profile of genes showing increased expression following dopamine and
      methamphetamine exposure in an immortalized neuronal cell line.
AB  - Methamphetamine (METH) is a drug of abuse with well-described neurodegenerative
      effects. Some of the METH-induced degenerative manifestations are thought to be
      due to increased dopamine (DA) release in the cytoplasm of nerve terminals and
      subsequent extravasation in the synaptic cleft. Using an immortalized neural cell
      line, we have made use of the comprehensive cDNA array technology in order to
      compare and contrast the molecular effects of DA and METH. We found that the two
      compounds do have many similar but also different effects. Since these neural
      cells produce no DA, these results demonstrate that many of the METH-induced
      responses attributed to DA might, in fact, be intrinsic to METH itself. More
      biochemical studies are needed to investigate DA-independent METH deleterious
      events in the central nervous system.

PMID- 11847429
TI  - Gene expression profile in early stage of retinoic acid-induced differentiation
      of human SH-SY5Y neuroblastoma cells.
AB  - PURPOSE: The human SH-SY5Y cell line is an established model for retinoic acid
      (RA)-induced neural differentiation. We employed a broad human 15K microarray
      (15,000 genes) and focused Neuroarray (1152 genes) to examine changes in gene
      expression early in the process of differentiation (6 hr), before morphology or
      growth changes are observed. METHODS: 33 P-labeled CDNA probes prepared from RNA
      extracts of RA-treated and control cultures were hybridized to array membranes,
      and levels of expression were quantified and compared. RESULTS: In the 15K array,
      19 % of the genes were decreased (0.4 % were named genes and the remainder were
      expressed sequence tags (ESTs) or unknowns), and 9 % were increased (4.2 % named
      genes). In the Neuroarray, 3 % were decreased and 8 % were increased.
      CONCLUSIONS: Summary gene profiles are presented, which include transcription
      factors, genes associated with cell cycle, cell shape, neurotransmission,
      intermediary filaments, and others. The prevalence of down-regulated genes in the
      broad 15K array and up-regulated genes in the neuro-focused array suggests a
      pattern shift in gene expression associated with differentiation. The
      predominance of ESTs among the down-regulated genes indicates a great number of
      as-yet-unidentified genes are repressed in early stage neural differentiation.

PMID- 11847430
TI  - A gene expression profile of embryonic stem cells and embryonic stem cell-derived
      neurons.
AB  - Embryonic stem (ES) cells have the ability to differentiate into a variety of
      cell lineages. We are examining ES cell differentiation in vitro by using cDNA
      microarrays to generate a molecular phenotype for each cell type. El4 ES cells
      induced by retinoic acid after forming embryoid bodies differentiate almost
      exclusively to neurons. We obtained expression patterns for about 8500 gene
      sequences by comparing mRNAs from undifferentiated ES cells and their
      differentiated derivatives in a competitive hybridization. Our results indicate
      that the genes expressed by ES cells change dramatically as they differentiate
      (58 gene sequences up-regulated, 34 down-regulated). Most notably, totipotent ES
      cells expressed high levels of a repressor of Hox expression (the polycomb
      homolog Mphl) and a co-repressor (CTBP2). Expression of these genes was
      undetectable in differentiated cells; the ES cell-derived neurons expressed a
      different set of transcriptional regulators, as weil as markers of neurogenesis.
      The gene expression profiles indicate that ES cells actively suppress
      differentiation by transcriptional repression; cell-cell contact in embryoid
      bodies and retinoic acid treatment may overcome this suppression, allowing
      expression of Hox genes and inducing a suite of neuronal genes. Gene expression
      profiles will be a useful outcome measure for comparing in vitro treatments of
      differentiating ES cells and other stem cells. Also, knowing the molecule
      phenotype of transplantable cells will allow correlation of phenotype with the
      success of the transplant.

PMID- 11847431
TI  - The use of representational difference analysis and cDNA microarrays in neural
      repair research.
AB  - Genetic subtraction studies may be useful tools for neural repair research by
      identifying genes expressed under one condition, but not under another. However,
      these studies suffer from some limitations, including a lack of heterogeneity of
      subtracted cDNA pools and the difficulty of screening out false positives in the
      subtracted pools. Our strategy to overcome these difficulties was to combine one
      subtractive method - representational difference analysis - with screening of the
      subtracted products using a custom CDNA microarray. Using the neurosphere culture
      system, we have used this stepwise approach in order to identify genes that are
      selectively expressed by CNS progenitor cells, but not by more differentiated
      cells. Following microarray screening, we confirmed the localization of
      putatively differentially expressed clones by in situ hybridization analysis.
      These genes, both novel and previously identified, now become candidate
      therapeutic targets for CNS repair strategies

PMID- 11847432
TI  - DNA microarray analysis of differential gene expression of 6-year-old rat neural
      striatal progenitor cells during early differentiation.
AB  - EGF-responsive striatal progenitor cells from rat brain have been maintained in
      culture in the form of neurospheres for six years without exhausting their
      renewal capacity. The events surrounding differentiation of stem cells in the
      brain after a long progenitorship remain a mystery. Using DNA microarray analysis
      we investigated differential gene expression, comparing progenitor cells in their
      neurosphere state with the cells 24 hours after induction of differentiation.
      Eighty-one genes showed increased expression in the differentiated condition.
      Genes associated with cellular growth, neurite outgrowth, and synaptogenesis were
      activated, including both anti-apoptotic and pro-apoptotic genes. Two transmitter
      related genes, acetylcholine receptor-beta and glutamate receptor-beta-unit were
      also elevated-, these genes not only fit the profile of early neural development,
      but also reflect the characteristics of striatal neurons. In addition, there are
      approximately 30 expressed sequence tags (ES7) increased during neural
      differentiation. Forty-seven genes showed decreased expression; half of them are
      known genes related to the cell cycle, cell adhesion, transcription, and
      signaling. Tbe signaling and cell cycle genes may be responsible for the life
      long self-renewal. These data demonstrate for the first time that life-long
      quiescent stem cells retain the potential to become activated and develop into
      specific types of brain cells. The six-year long-term neural stem cells are an
      excellent model for studying developmental neurobiological processes and aging.

PMID- 11847433
TI  - The assessment of genomic alterations using DNA arrays following traumatic brain
      injury: a review.
AB  - Recent advances in DNA microarray technology have enabled the simultaneous
      evaluation of thousands of genes and the subsequent generation of massive amounts
      of biological data relevant to injury or diseases of the central nervous system
      (CNS). This technology has the potential to bridge the gap between molecular and
      systems neuroscience by efficiently revealing the discrete molecular aspects
      underlying the perturbations of complex systemic insults such as those resulting
      from traumatic brain injury (TBI). One of the more intriguing and as of yet not
      understood aspects of TBI that can be efficiently explored with DNA microarrays,
      is the sequence of molecular events that results in pronounced cell death in
      specific areas of the brain. The elucidation of these changes in gene expression
      underlying the mechanism of cell death following brain injury is of central
      importance in the design of future therapeutic agents. This review focuses on the
      technical aspects of microarray manufacture (photolithography, microspotting, and
      ink jet technology) and their utility in elucidating the molecular sequelae of
      brain injury.

PMID- 11847434
TI  - Evidence for shared genetic programs from cluster analysis of hippocampal gene
      expression dynamics in development and response to injury.
AB  - Cluster analysis is a computational method that groups together similarly-shaped
      patterns. It may be applied to large-scale gene expression data to form new
      hypotheses regarding gene function. In the present study, we clustered the
      temporal expression patterns of genes expressed in the rat hippocampus during
      normal development and after a kainate-induced seizure injury at postnatal day
      25. We found that two different methods, Euclidean hierarchical and K-means
      clustering, produced slightly different results, and concluded that different
      clustering methods may he used to complement one another. We also found that
      certain genes cluster together both during development and after seizure injury,
      consistent with the idea of sets of genes that act in concert under various
      conditions.

PMID- 11847435
TI  - Assembly and use of a broadly applicable neural cDNA microarray.
AB  - cDNA microarrays provide an efficient method to analyze gene expression patterns
      in thousands of genes in parallel. In some cases, large unfocused collections of
      cDNAs have been used in hybridization studies, in others small logically defined
      collections of tissue specific arrays have been used. Here we describe the
      bioinformatic selection of 1152 named human cDNAs specifically designed for
      neuroscience applications, arrayed on nylon membranes at high density. cDNAs were
      chosen which represent all the major cellular types of the brain including;
      neurons, astrocytes, microglia, and oligodendrocytes. Gene families chosen
      include cell type specific markers, ion-channels, transporters, receptors, and
      cell adhesion molecules among many others. These arrays were used with region
      specific samples from human brain to determine MRNA expression profiles for each
      region. Used with 33p labeled complex probes, this is a low cost, highly
      sensitive approach for tbc investigator to focus on tissue specific genes of
      interest where samples of limiting amounts of RNA are used. This selected set of
      brain-relevant cDNAs should be widely useful in the analysis of gene expression
      patterns from brain tissues as well as neural cell lines.

PMID- 11847436
TI  - From cDNA microarrays to high-throughput proteomics. Implications in the search
      for preventive initiatives to slow the clinical progression of Alzheimer's
      disease dementia.
AB  - Alzheimer's disease (AD) is the most common form of dementia, affecting as many
      as four million elderly people. lt results from abnormal changes in the brain
      that most likely begin long before cognitive impairment and other clinical
      symptoms become apparent. Little is known about the changes preceding or
      accompanying initiation of the disease. Using cDNA microarray, we previously
      reported candidate gene products whose expression is altered in the cerebral
      cortex of cases at risk for AD dementia. However, it is possible that the cDNA
      microarray evidence might have underestimated post-transcriptional modifications,
      and as a result, provided only a partial view of the biological problem of
      interest. Based on this hypothesis, we initiated a series of parallel high
      throughput proteomic studies. We found that, consistent with the cDNA microarray
      evidence, the expression of proteins involved in synaptic activities was also
      altered in the brains of early AD cases. These studies support the feasibility
      and usefulness of high-throughput cDNA and protein microarray techniques to
      examine the sequential changes of distinctive gene expression patterns in the
      brain as a function of the progression of AD dementia. Our preliminary results
      also support the utility of high-throughput proteomic methodologies as a means to
      identify novel AD biomarkers from cerebral spinal fluid and/or from serum.

PMID- 11847437
TI  - Differential effect of the alpha2-adrenoceptor antagonist, atipamezole, in limb
      placing task and skilled forepaw use following experimental stroke.
AB  - PURPOSE: Tbc present study compared tbc effect of chronic administration of the
      selective alpha2-adrenoceptor antagonist, atipamezole, on performance in
      behavioral tests that differ in motoric complexity in two experimental stroke
      models. METHODS: Transient occlusion (120 min) of the middle cerebral artery
      (MCA) using the intraluminal method was used to produce corticostriatal infarcts
      and permanent occlusion of distal MCA by electrocoagulation was used to produce
      cortical infarcts. Chronic atipamezole treatment (1 mg/kg, s.c., once per day)
      was started 2 days after ischemia induction and continued until the end of the
      experiment, 35 days after ischemia induction. Behavioral performance of the
      operated rats was assessed 30 min after drug administration using the limb
      placing test and Montoya's staircase test. RESULTS: Atipamezole facilitated
      spontaneous recovery in the limb-placing task particularly in rats subjected to
      transient MCA occlusion. The analysis of retrieved pellets in Montoya's staircase
      test suggests that there is no recovery (Time effect, P > 0.05) in the use of the
      impaired forelimb (contralateral-to-lesion) following transient MCA occlusion,
      whereas there was some recovery following permanent MCA occlusion (Time effect, P
      < 0.001). The impairment was bilateral in rats subjected to transient MCA
      occlusion. Atipamezole treatment did not affect the use of the impaired forelimb
      to retrieve pellets following transient MCA occlusion, but there was a tendency
      to facilitate impaired forelimb use following permanent MCA occlusion
      (Time*Treatment interaction, P = 0.086). CONCLUSION: Transient occlusion of the
      MCA produced a severe, long lasting, and bilateral deficit in skilled forelimb
      use. Permanent occlusion of the distal MCA was associated with less severe
      impairment, which was alleviated to some extent by administration of atipamezole.
      This is in contrast to spontaneous recovery and recovery-enhancing effects of
      atipamezole in the limb-placing test, particularly in the transient MCA occlusion
      model.

PMID- 11847439
TI  - Effects of the duration of progesterone treatment on the resolution of cerebral
      edema induced by cortical contusions in rats.
AB  - PURPOSE. The aim of the present study was to assess the effect of different
      durations of administration of progesterone (4 mg/kg) on the resolution of edema
      6 days after medial frontal cortex contusions (MFC) in male adult rats. METHODS:
      Animals sustaining injury were injected with progesterone or its vehicle for 3
      days or for 5 days beginning the first hour after surgery. On the 6th day the
      rats were killed and their brain water content was measured. RESULTS: We
      confirmed the presence of edema six days after MFC. However, both 3 and 5 days of
      treatment with progesterone significantly reduced edema in the injured brains but
      the five days of treatment were more effective. The effects of progesterone
      depend upon the duration of the treatment because there are two waves of edema.
      The first phase begins within a few hours of the injury and the second starts
      several days later. CONCLUSIONS: Our data are consistent with earlier findings
      showing that longer durations of progesterone administration lead to more
      complete behavioral recovery as well as to an increased number of surviving
      neurons.

PMID- 11847438
TI  - Conditioning hypoxia in vivo alters neuronal excitability of hippocampal neurones
      of rats in vitro and in vivo.
AB  - PURPOSE: Moderate normobaric hypoxia causes long-lasting protection against
      damage induced by a second ischemic or traumatic insult. The changes induced by
      such conditioning hypoxia are not yet fully understood. The protective effect has
      been described in various publications but other effects seem possible. METHODS:
      In order to search for effects of conditioning normobaric hypoxia yet unknown, we
      measured O-Mg++ potentiation and classical long-term potentiation (LTP) in the
      CA, region of hippocampal slices seven days after the conditioning procedure.
      Furthermore, tests were also carried out in chronically implanted rats as to
      whether LTP was changed in the dentate gyrus after conditioning hypoxia. RESULTS:
      In slices taken from animals which received conditioning hypoxia, O-Mg++
      potentiation and classical LTP of the population spike were significantly
      enhanced, when compared to population in two control groups. Anoxic LTP, i.e.
      increase in the population spike of the field potential in the dentate gyrus
      immediately after finishing the procedure, and a tendency to elevation of LTP
      seven days after conditioning were also found in chronically implanted animals
      which were subjected to conditioning hypoxia. CONCLUSIONS: lt. may be
      hypothesized that elevated Ca++ transport in the neurons during conditioning
      hypoxia is responsible for both long- lasting increases in plastic reactions and
      the protective effect.

PMID- 11847441
TI  - Restoration of vision IV: role of compensatory soma swelling of surviving retinal
      ganglion cells in recovery of vision after optic nerve crush.
AB  - PURPOSE: Diffuse axonal injury following partial optic nerve crush (ONC) leads to
      severe visual deficits from which rats can partially recover within 2-3 weeks. To
      evaluate tbc role of surviving retinal ganglion cells (RGCS) in recovery, we have
      observed their morphology repeatedly in vivo with ICON-microscopy and correlated
      cell size changes with recovery of vision which we observed in parallel in the
      same animals. METHODS: After rats had learned a visual contrast discrimination
      task using an automated, computer-based test, RGCs were labeled retrogradely with
      fluorescent beads. Animals then received either no lesion, a complete axotomy or
      bilateral mild, moderate or severe ONC. Before surgery and for 40 days post
      operatively, ROC number and soma size was repeatedly quantified every five days
      with tbc in vivo confocal neuroimaging method (Sabel et al., Nature med. 3, 1997,
      p. 244). In parallel, visual function was quantified with the contrast
      discrimination task. RESULTS: After ONC about 70 % of the ROCs died after having
      undergone a fast and massive soma swelling. The extent of cell death was
      independent of crush severity. RGCs surviving the injury did not change their
      body size over time in the severe group and these animals also did not recover
      their vision. In contrast, after a mild or moderate crush, about half of the
      surviving RGCs experienced a slow and moderate, "compensatory" cell soma swelling
      and the rats showed partial recovery of vision. Both the number of RGCs showing
      such compensatory soma swelling and the extent of the swelling correlated highly
      (r = 0.96) with recovery of contrast discrimination performance at post-operative
      days 23 and 38. CONCLUSIONS: Depending en the time course and extent, soma
      swelling after neurotrauma may be associated either with cell death or recovery
      of function. Because of the very high correlation between extent of recovery and
      amount of soma swelling, moderate soma swelling contributes in a prominent way to
      recovery of vision. We believe that these cells provide an important structural
      substrate for neuronal tissue repair and therefore term these cells "compensatory
      neurons".

PMID- 11847440
TI  - Nerve growth factor and neurotrophin-3 affect functional recovery following
      peripheral nerve injury differently.
AB  - PURPOSE: Many studies have investigated the roles of neurotrophic factors in
      nerve regeneration by examining either anatomical recovery (regenerated axon
      count) or functional recovery as measured by sensory and motor behavior. This
      longitudinal study examined the effects of NGF and NT3 on functional and
      anatomical recovery following transection of tbc sciatic nerve. METHODS: Alzet
      osmotic pumps were implanted to deliver a continuous supply of NGF, NT3 or buffer
      solution to the stumps of the transected sciatic nerve for the first 28 days
      following implantation. Rats were tested weekly to determine the extent of
      recovery of motor (footprint gait analysis) or nociceptive (warm water
      withdrawal), and mechanoreceptive (skin pinch) function. RESULTS: Neither NT3-,
      nor NGF-treatment significantly enhanced motor recovery as examined by gait
      analysis. At the end of 12 weeks of behavioral testing, there was no difference
      in motor recovery. In addition, the recovery of withdrawal response to warm water
      stimulus was delayed in NGF treated animals. After twelve weeks, nerves were
      removed for anatomical analysis. Regenerated sciatic nerves from NT3 treated
      animals had slightly more axons than control- or NGF-treated animals. CONCLUSION:
      This work shows that there were no long-lasting improvements of anatomical or
      functional recovery in NGF- or NT3-treated animals 12 weeks following sciatic
      nerve transection.

PMID- 11847442
TI  - Androgenic enhancement of betaII-tubulin mRNA in spinal motoneurons following
      sciatic nerve injury.
AB  - PURPOSE: We have previously demonstrated that systemic administration of
      testosterone propionate (TP) can accelerate the functional recovery from hind
      limb paralysis following sciatic nerve injury in the rat. In this study, we
      looked at the molecular mechanisms underlying this phenomenon. METHODS: Castrated
      adult male rats received a right side sciatic nerve crush at the level of the
      sciatic notch, with the left side serving as control. Half the animals received a
      subcutaneous implant of TP, the others were sham implanted. Animals were
      sacrificed at 1, 3, 7 and 10 days post-operative. Lumbar spinal cord tissue was
      harvested and in situ hybridization was performed using a cytoskeletal cDNA probe
      complementary to betaII-tubulin. RESULTS: On the injured side, sciatic motoneuron
      tubulin mRNA levels were increased in alt groups at alt time points. At 3 and 7
      days post- op, the TP treated group had significantly higher levels of tubulin
      mRNA. CONCLUSIONS: These results suggest that testosterone enhances the rate of
      regeneration by increasing the neuronal cytoskeletal response after axonal
      injury. Further, these results, coupled with the results from previous
      experiments in other rodent models, suggest a common mechanism for gonadal
      steroid action on regenerating motoneurons across species.

PMID- 11847443
TI  - Telemedicine: issues and implications.
AB  - Physicians, hospitals and medical schools have been exploring the uses of
      telemedicine since 1964, primarily in the area of medical education. While the
      explosion of interest in telemedicine over the past five or six years has seen an
      increase in the use of telecommunications technology. At present, telemedicine is
      utilised by health providers in a growing number of medical specialties including
      but not limited to: dermatology, oncology, radiology, surgery, cardiology,
      psychiatry and home health care. The emergence of telemedicine has altered the
      structure of this industry, the management of the health providers and is likely
      to have an impact on the patients and society at large.

PMID- 11847445
TI  - A biomechanical study of the finger pulley system during repair.
AB  - This paper addresses the mechanics of the finger/pulley system when subjected to
      various excisions and repairs. Several cadaver hands were used to study the
      finger/pulley's function, finger joint dynamics, and the relationship between
      tendon excursion and finger joint angles of rotation. By using a method of
      continuous and simultaneous data acquisition of the entire finger joint's motion,
      a more detailed analysis was achieved. Our experimental investigation is based on
      the use of four micro-potentiometers inserted at the finger's joints and a pulley
      system to simulate tendon excursion. Using this procedure, a detailed kinematic
      analysis of the entire finger was performed. This included analysis of the intact
      hand, various pulley excisions, and reconstruction. In addition to introducing a
      new method of acquisition, a mathematical model was developed for the inverse
      dynamic analysis of the finger pulley system. From this model, the torques
      required at the joints for the motion were computed. The results provided new
      insight into possible ways of characterizing kinematic changes resulting from
      pulley damage and repair.

PMID- 11847444
TI  - The calculation of the intramyocardial stress.
AB  - A mathematical approach is given by which the intramyocardial stress sigma
      induced in the passive medium of the myocardium is expressed as the sum of the
      stress (sigma)p induced in the passive medium by the left ventricular pressure P
      and the external pressure Po, and the stress(sigma)d induced in the passive
      medium by the active force generated by the muscular fibers of the myocardium.
      Relations between sigma = (sigma)p + (sigma)d, the left ventricular elastance E
      and the residual volume Vd are also derived. Applications to experimental data
      are given and clinical implications of the results are discussed.

PMID- 11847446
TI  - Treatment of extrahepatic bile duct disease in infancy and early childhood.
AB  - Extrahepatic bile duct disease is a rare finding in infancy and early childhood.
      However, there is an increasing number of patients operated at this age reported
      in the literature. This increase may have multifactorial reasons, e.g. real
      increase, better ability of detection as a result of better diagnostic techniques
      and knowledge of predisposing factors of extrahepatic bile duct disease in
      childhood, especially in early childhood and infancy. The following report
      describes three cases of extrahepatic bile duct disease in infancy and early
      childhood treated at the Department of Surgery of the University of Technology in
      Aachen, Germany. From 1986 to 1998 28 Patients below 18 years were operated at
      our Department of Surgery. There was a recognizable increase of patients in 1996,
      1997 and 1998. Whereas from 1986 to 1995 an average of 1.5 Cholecystectomies in
      pediatric patients were done, the years from 1996 to 1998 show an average of 5,33
      patients operated per year. Every patient obtained a Cholecystectomy -- 15
      conventional open Cholecystectomies and 13 Laparoscopies, which were primarily
      performed in children in our clinic in 1991. Besides cholecystectomy in one case
      a Hepaticoenterostomy was necessary and in another case surgical treatment of the
      Papilla of Vater and the Common Bile Duct was performed. In 22 patients
      symptomatic Cholelithiasis was the indication for a Cholecystectomy. Another
      Patient had a gallbladder polyp consisting of heterotopic Duodenal glands, two
      patients showed a shock gallbladder following trauma and cardiac operation and
      three patients had chronic Cholecystitis without gallstones. Clinical data was
      collected and retrospectively reviewed. Additionally, we created a personal
      questionnaire to carry through a follow-up. Three Patients were less than 3 1/2
      years old. The youngest patient was only 5 months old and presented with
      Cholelithiasis and Choledocholithiasis. Another male patient, aged 2 years
      received a Cholecystectomy and a Hepaticoenterostomy because of a Choledochal
      Cyst Type Ib (Todani-Classification). And a 3-year-old-girl had a shock
      gallbladder caused by thromboembolism following cardiac operation nine days
      before.

PMID- 11847447
TI  - The area of the pressure-flow loop for assessment of arterial stenosis: a new
      index.
AB  - This study describes a novel method for assessing stenotic severity, based on
      simultaneous pressure and flow wave measurements. Pressure and flow measurements
      were performed in latex and rubber tubes, and in a clinically-used vascular
      graft. Pressure waves were recorded at several degrees of stenosis and at
      different distances proximal to the stenosis. Pressure wave versus flow wave was
      plotted. Internal pressure-flow loop area (PFLA), loop slope and pressure-axis
      intercept were calculated. Values of these three indices significantly increased
      with increasing degrees of stenosis P < 0.001). Similar phenomenon was observed
      during in-vivo experiments. Polynomial functions were fitted, resulting in an
      excellent PFLA variable/ percent stenosis correlation, independent of distance
      between sensor and stenosis (R2 > 0.96). In addition, tube compliance was
      measured and found to correlate with the polynomial coefficients (/R/ > 0.9).
      This innovative approach could significantly contribute to detecting and
      evaluating arterial stenoses, and to characterize the elasticity of the artery.

PMID- 11847448
TI  - Effect of contrast agent viscosity and injection flow velocity on bolus injection
      pressures for peripheral venous injection in first-pass myocardial perfusion
      studies.
AB  - Myocardial perfusion imaging using Gd contrast agents is typically performed with
      bolus injections of the contrast agent using a power injector to provide for
      consistent and sufficiently rapid injection rates for all patients. For protocols
      in which a peripheral venous injection is called for (e.g. antecubital vein)
      injection catheters of 18 ga are used where vessel geometry permits. In some
      patients, particularly women with smaller veins, 20 and 22 ga catheters are used.
      The effect of catheter size and pressure tubing length can result in high
      injection pressures that occasionally cause leakage or connector failure. The
      viscosity of the contrast agent also impacts injection pressure. In this study, a
      simulation of the injection pathway was constructed with time resolved pressures
      measured at two points in the pathway. Pressure drops were calculated for a
      typical MR perfusion injection protocol.

PMID- 11847449
TI  - Development and modelling of arterial applanation tonometry: a review.
AB  - Arterial tonometry allows non-invasive and continuous registration of the
      arterial pressure waveform, by applanating (flattening) a superficial artery
      supported by bone with an external transducer. Inspired by ocular tonometry used
      for eye disease diagnosis, G.L. Pressman and P.M. Newgard built the first
      arterial tonometer in 1963, and derived a discrete, linear mechanical model.
      Accuracy remained poor until new sensor production techniques (silicon
      technology) arrived. G.M. Drzewiecki et al. published a second, more elaborate
      theoretical model for tonometer positioning in 1983. Few years later, the first
      modern tonometers were commercialised. Although the problems of sensor
      positioning, motion artefacts and calibration still exist, the tonometer has
      proven its usefulness in arterial compliance and hypertension studies. Attention
      should now go to analysis of the arterial pressure waveforms, and the combination
      with other signals (e.g. flow wave morphology) to allow a complete non-invasive
      haemodynamical description of the heart and the arterial tree.

PMID- 11847450
TI  - Expression of inducible nitric oxide synthase (iNOS/NOS II) in the hydropic
      vestibule after injection of keyhole limpet hemocyanin into the endolymphatic sac
      of guinea pigs.
AB  - This study was undertaken to examine the expression of inducible nitric oxide
      synthase (iNOS / NOS II) in the hydropic vestibule of guinea pigs. Animals were
      systemically sensitized with 500 microg of keyhole limpet hemocyanin. Two weeks
      after the first injection, keyhole limpet hemocyanin (100 microg/5 microl) was
      injected into the endolymphatic sac following the intradural approach, and the
      next day temporal bones were removed for the immunohistochemical examination.
      Endolymphatic hydrops was evidenced by the expansion of the Reissner's membrane
      in the cochlea after direct injection of keyhole limpet hemocyanin into the
      endolymphatic sac. Inducible nitric oxide synthase expression was increased in
      the sensory cells, supporting cells and vestibular ganglion cells, while temporal
      bones, where only phosphate buffered saline was injected, did not show any
      inducible nitric oxide synthase immunoreactivity. High levels of inducible nitric
      oxide synthase-catalyzed nitric oxide were detected prior to the development of
      the inner ear dysfunction. Our results suggest that the occurrence of inducible
      nitric oxide synthase immunoreactivity parallels the inner ear disturbance as
      seen in endolymphatic hydrops.

PMID- 11847451
TI  - Effects on the optokinetic system of midline lesions in the pretectum of monkeys.
AB  - The nucleus of the optic tract (NOT), an important visuo-motor relay between the
      retina and preoculomotor structures, is responsible for mediating horizontal
      optokinetic nystagmus (OKN) in monkeys, cats, rabbits and rats. In addition to
      its projection to the vestibular nuclei, the NOT has a prominent projection to
      the contralateral NOT via the posterior commissure. In order to evaluate the role
      of the commissural fibers between the NOTs in OKN, we cut the posterior
      commissure in three Macaca fuscata. The animals viewed the OKN stripes under
      three conditions: right eye viewing, left eye viewing, and both eyes viewing. OKN
      was recorded in response to counter-clockwise and clockwise stimulation at
      stimulus velocities of 30 degrees/s, 60 degrees/s and 90 degrees/s. After control
      data were gathered, the posterior commissure was transected with an operating
      knife. Before the animal was sacrificed, biocytin, an anterograde tracer, was
      injected into the left NOT in order to confirm that all of the commissural fibers
      had been cut. Although the midline lesions decreased the initial rapid rise and
      steady state OKN slow-phase velocity in all three animals, there were no
      directional differences observed during monocular clockwise or counter-clockwise
      visual stimulation to either eye. In two of the three animals, there were no
      significant differences in the time-constants of optokinetic after nystagmus
      (OKAN) after the lesion. In the remaining animal, the time-constants decreased at
      stimulus velocities of 30 degrees/s and 60 degrees/s. In conclusion, gain
      reduction in the rapid rise and steady state slow-phase velocity of OKN can be
      explained by removal of an excitatory signal mediated by commissural fibers to
      inhibitory interneurons in the contralateral NOT. However, interrupting the
      commissural fibers had no effect on the velocity storage mechanism, because the
      time-constants of OKAN mostly remained largely unchanged by the lesion.

PMID- 11847452
TI  - The human oculomotor response to simultaneous visual and physical movements at
      two different frequencies.
AB  - In order to investigate interactions in the visual and vestibular systems'
      oculomotor response to linear movement, we developed a two-frequency stimulation
      technique. Thirteen subjects lay on their backs and were oscillated sinusoidally
      along their z-axes at between 0.31 and 0.81 Hz. During the oscillation subjects
      viewed a large, high-contrast, visual pattern oscillating in the same direction
      as the physical motion but at a different, non-harmonically related frequency.
      The evoked eye movements were measured by video-oculography and spectrally
      analysed. We found significant signal level at the sum and difference frequencies
      as well as at other frequencies not present in either stimulus. The emergence of
      new frequencies indicates non-linear processing consistent with an agreement
      detector system that have previously proposed.

PMID- 11847453
TI  - Effect of aging on the otolith-ocular reflex.
AB  - We assessed the influence of age on the otolith-ocular reflex and semicircular
      canal-otolith interaction. Healthy young (n=30) and healthy older (n=60) subjects
      were rotated about an earth vertical axis, and about a 30 degree off-vertical
      axis. Eye movements during and following rotation were recorded using electro
      oculography. Results indicated that there were statistically significant changes
      in the otolith-ocular reflex and semicircular canal-otolith interaction as a
      function of age. The modulation component during off-vertical axis rotation
      (OVAR) was greater in the older group compard to the young adults, whereas the
      bias component was smaller with advanced age. The foreshortening of the vestibulo
      ocular reflex time constant induced by post-rotatory head tilt following
      cessation of rotation was less prominent in the older group. There were no
      consistent changes in the semicircular canal-ocular reflex. Overall, response
      parameters showed more variability in the older subjects. We conclude that age
      related changes in the otolith-ocular reflex and semicircular canal-otolith
      interaction are a result primarily of a degradation of central vestibular
      processing of otolith signals rather than a decline of peripheral vestibular
      function.

PMID- 11847454
TI  - Head stability in older adults during walking with and without visual input.
AB  - The purposes of this study were to 1) characterize head stabilization in older
      adults across the frequency spectrum of walking, and 2) assess the ability of
      older adults to adapt head-trunk coordination to maintain head stability in the
      absence of vision. Sagittal plane head and trunk angular velocities in space were
      measured for 17 healthy older adults while walking with eyes open (EO) and eyes
      closed (EC). Average walking velocity and cadence were also determined. Frequency
      analyses were used to examine head velocities in space and head-on-trunk with
      respect to trunk gain and phase values across the frequency spectrum of walking.
      Average walking velocity decreased with EC. Head stability was maintained during
      EO, but decreased during EC as indicated by increased head velocities across the
      frequency spectrum. Gain values increased while phase values remained similar
      during EC walking demonstrating diminished coordination of head-trunk movements.
      When relying on vestibular and proprioceptive information, older adults were
      unable to adapt head-trunk movements suggesting impaired plasticity of these
      systems with age.

PMID- 11847456
TI  - The menstrual cycle and susceptibility to coriolis-induced sickness.
AB  - Survey studies on motion sickness susceptibility suggest that females tend to
      report greater severity in illness and higher incidence of vomiting than males.
      Menstruation is said to be a contributing factor. A recent study suggested that
      females were least susceptible to seasickness during ovulation in a "round the
      world" yacht race. Sixteen subjects (18-36 years old) were exposed to Coriolis
      cross-coupling stimulation in the laboratory. They were tested once during
      permenstruation (Day 1-5), ovulation (Day 12-15) and premenstruation (Day 24-28),
      based on a normalized 28-day cycle, in a randomised design. Physiological
      measurements of motion sickness included forearm and calf cutaneous blood flow.
      Subjective evaluation of sickness symptoms was based on Graybiel's diagnostic
      criteria and Golding's rating method. Our results indicated that under controlled
      laboratory conditions, different phases of the menstrual cycle appear to have no
      influence on subjective symptoms of motion sickness or on cutaneous blood flow
      increase in the forearm and calf. The lack of commonality between the types and
      levels of hormones that are released during motion sickness and those that are
      involved in different menstrual phases appears to support our findings.

PMID- 11847455
TI  - Orientation illusions and heart-rate changes during short-radius centrifugation.
AB  - Intermittent short-radius centrifugation is a promising countermeasure against
      the adverse effects of prolonged weightlessness. To assess the feasibility of
      this countermeasure, we need to understand the disturbing sensory effects that
      accompany some movements carried out during rotation. We tested 20 subjects who
      executed yaw and pitch head movements while rotating at constant angular
      velocity. They were supine with their main body axis perpendicular to earth
      gravity. The head was placed at the centrifuge's axis of rotation. Head movements
      produced a transient elevation of heart-rate. All observers reported head
      contingent sensations of body tilt although their bodies remained supine. Mostly,
      the subjective sensations conform to a model based on semicircular canal
      responses to angular acceleration. However, some surprising deviations from the
      model were found. Also, large inter-individual differences in direction,
      magnitude, and quality of the illusory body tilt were observed. The results have
      implications for subject screening and prediction of subjective tolerance for
      centrifugation.

PMID- 11847457
TI  - Indications for surgery in necrotizing pancreatitis--a millennial review.

PMID- 11847458
TI  - Allograft pancreatic duct dilatation following bladder drained simultaneous
      pancreas-kidney transplantation: clinical significance.
AB  - OBJECTIVE: Radiologic imaging of the allograft pancreatic duct dilatation is an
      uncommon multifactorial finding that is not well described. The purpose of this
      investigation is to determine the clinical correlation of this finding. DESIGN:
      Retrospective study. SETTING: University Hospital, USA. SUBJECTS: One hundred
      forty five simultaneous pancreas-kidney transplants have been performed for
      treatment of type I diabetes mellitus and end-stage renal disease between
      February 1993 and December 1999 at the University of Miami. MAIN OUTCOME
      MEASURES: In 5 recipients, the pancreatic duct was noted to be dilated by
      ultrasound 1-18 months post-transplant. RESULTS: In all 5 recipients a Foley
      catheter was placed as the first line of treatment. This reduced the size of the
      pancreatic duct in one patient, who presented with normal serum amylase and
      lipase and hyperglycemia. A pancreas biopsy done with Foley catheter in place
      showed fibrosis with no evidence of rejection. Four patients with dilated
      pancreatic duct presented with increased serum amylase and lipase; however
      improvement of the pancreatic duct dilatation was seen only after anti-rejection
      therapy. One of the patients developed recurrence of pancreatic duct dilatation
      and a video-urodynamic study subsequently demonstrated voiding with abdominal
      straining and no detrusor activity. He ultimately underwent enteric conversion
      with resolution of pancreatic duct dilatation. CONCLUSIONS: This infrequent
      complication of dilated transplant pancreatic duct could be multifactorial. It
      could suggest the diagnosis of reflux pancreatitis, which should resolve with
      bladder decompression. In fact, 1 patient presented with reflux pancreatitis
      caused by external sphincter detrusor pseudodyssynergia. However, this ultrasound
      finding may also be associated with pancreas rejection (4/5 patients).

PMID- 11847459
TI  - The metabolism of the pancreas carcinogen N-nitrosobis(2-oxopropyl)amine by
      hamster pancreas duct epithelial cell clones; evidence for different metabolic
      efficiencies and response to cytochrome P450 inducers.
AB  - CONTEXT: We have isolated five stable clones from a primary culture of Syrian
      golden hamster pancreatic duct epithelial cells and have designated them as CK1
      through CK5. DESIGN: Here we describe the ability of two of these, CK1 and CK5,
      to metabolize the pancreas carcinogen N-nitrosobis(2-oxopropyl)amine. The
      metabolism was assessed as the production of mutated V79 cells in a CK cell/V79
      co-culture set up. RESULTS: At a dose of 0.1 mM N-nitrosobis(2-oxopropyl)amine,
      the CK1 cells produced 82.3 +/- 17.2 mutants/1,000,000 survivors while the CK5
      cells produced only 33.2 +/- 10.8 mutants/1,000,000 survivors, both are mean +/-
      SD (n = 8). Furthermore, both cell types responded differently to two inducers of
      cytochrome P450 activity, namely Arochlor 1254 and EtOH. Arochlor 1254 treatment
      did not affect the metabolizing ability of CK1 cells while EtOH treatment
      resulted in a twofold increase in the mutation frequency. Arochlor and EtOH
      treatment inhibited the ability of CK5 cells to metabolize N-nitrosobis(2
      oxopropyl)amine. CONCLUSIONS: These data show that the duct epithelium of the
      pancreas is a multi-cellular tissue and the different cell types within the
      epithelium have different abilities to metabolize xenobiotic chemicals.

PMID- 11847461
TI  - Deafness-induced changes in the auditory pathway: implications for cochlear
      implants.
AB  - A profound sensorineural hearing loss induces significant pathological and
      atrophic changes within the cochlea and central auditory pathway. We describe
      these deafness-induced morphological and functional changes following controlled
      lesions of the cochlea in experimental animals. Such changes are generally
      consistent with the limited number of reports describing deafness-induced changes
      observed in human material. The implications of these pathophysiological changes
      within the auditory pathway on cochlear implant function are discussed. Finally,
      the plastic response of the deafened auditory system to electrical stimulation of
      the auditory nerve is reviewed in light of the clinical implications for cochlear
      implant recipients.

PMID- 11847462
TI  - Activity-dependent plasticity in the adult auditory brainstem.
AB  - Over the past few years we have studied the plasticity of the adult auditory
      brainstem in the rat following unilateral changes to the pattern of sensory
      activation, either by intracochlear electrical stimulation or by deafening. We
      discovered that modifications to afferent activity induced changes in the
      molecular composition and cellular morphology throughout the auditory brainstem,
      including its major centers: the cochlear nucleus complex, the superior olivary
      complex, and the inferior colliculus. The time window studied ranged from 2 h to
      over 1 year following induction of changes to afferent activity. The molecular
      markers employed include the NMDA receptor subunit type 1, the cAMP response
      element binding protein (CREB), the immediate early gene products c-Fos, c-Jun
      and Egr-1, the growth and plasticity-associated protein GAP-43 and its mRNA, the
      calcium binding protein calbindin, the cell adhesion molecule integrin-alpha(1),
      the microtubule-associated protein MAP-1b, and the neurofilament light chain (NF
      L). As a consequence of the specific electrical stimulation of the auditory
      afferents or the loss of hearing, a cascade of events is triggered that
      apparently modifies the integrative action and computational abilities of the
      central auditory system. An attempt is made to relate the diverse phenomena
      observed to a common molecular signaling network that is suspected to bridge
      sensory experience to changes in the structure and function of the brain.
      Eventually, a thorough understanding of these events will be essential for the
      specific diagnosis of patients, optimal timing for implantation, and suitable
      parameters for running of a cochlear implant or an auditory brainstem implant in
      humans. In this report an overview of the results obtained in the past years in
      our lab is presented, flanked by an introduction into the history of plasticity
      research and a model proposed for intracellular signal cascades related to
      activity-dependent plasticity.

PMID- 11847463
TI  - Delayed maturation and sensitive periods in the auditory cortex.
AB  - Behavioral data indicate the existence of sensitive periods in the development of
      audition and language. Neurophysiological data demonstrate deficits in the
      cerebral cortex of auditory-deprived animals, mainly in reduced cochleotopy and
      deficits in corticocortical and corticothalamic loops. In addition to current
      spread in the cochlea, reduced cochleotopy leads to channel interactions after
      cochlear implantation. Deficits in corticocortical and corticothalamic loops
      interfere with normal processing of auditory activity in cortical areas. Thus,
      the deprived auditory cortex cannot mature normally in congenital deafness. This
      maturation can be achieved using auditory experience through cochlear implants.
      However, implantation is necessary within the sensitive period of the auditory
      system. The functional role of long-term potentiation and long-term depression,
      inhibition, cholinergic modulation and neurotrophins in auditory development and
      sensitive periods are discussed.

PMID- 11847464
TI  - Of kittens and kids: altered cortical maturation following profound deafness and
      cochlear implant use.
AB  - Profoundly deaf children who use a cochlear implant (CI) provide a unique
      opportunity to investigate the effects of auditory sensory deprivation on the
      maturing human central nervous system. Previous results suggest that children
      fitted with a CI show evidence of altered auditory cortical maturation, based on
      evoked potentials. This altered maturation was characterized by both latency
      delays and morphological changes in the cortical auditory evoked potentials
      (AEPs). Based on prolonged P(1) latencies compared to age-matched normal-hearing
      (NH) peers, these data suggested a delayed maturation nearly equivalent to the
      period of deafness. However, rates of maturation for this AEP peak were
      essentially the same in NH and CI children. This suggests that, given enough
      time, the AEPs of CI children would assume the characteristic morphology found in
      older NH teens and NH adults. However, the data also indicated a substantial
      alteration of the typical set of obligatory P(1)-N(1b)-P(2) peaks, specifically
      related to the absence of the N(1) potential. Recent analyses of more extensive
      sets of longitudinal and cross-sectional data indicate that even after many years
      of implant use, the AEPs of CI users in their late teens remain very different
      from those of their NH peers. The P(1) peak latency remains prolonged and P(1)
      amplitude remains much larger in CI users than in age-matched NH teens. These
      findings suggested that age-related changes in the P(1) peak are completed by 12
      years of age. In addition, the normal N(1b) peak fails to emerge in virtually all
      of the CI children tested in our laboratory. A major new interpretation of the
      abnormal maturation of AEP waveforms in CI children is presented. It is based on
      direct evidence showing that a persistent immaturity of the superficial layer
      axons has persistent negative effects on the generation of the N(1b) and,
      consequently, on the morphology of the AEPs. A comparison of scalp-recorded AEPs
      from implanted children with local field potentials measured from the cortical
      surface in deaf white kittens suggests the effects of deafness and CI use are
      similar across these mammalian species. For both species, a period of profound
      deafness followed by CI stimulation reveals a substantial immaturity in cortical
      activation even after a period of electrical stimulation by the CI.

PMID- 11847465
TI  - Imaging plasticity in cochlear implant patients.
AB  - Auditory re-afferentation by cochlear implants (CI) offers a unique opportunity
      to study directly from within the auditory modality plastic changes taking place
      at organisational levels up to the supra- or polymodal level. These plastic
      changes resulting from deafness and chronic electrical stimulation can be studied
      using modern neuroimaging techniques. In this paper, we review the available
      techniques and the experimental approaches to human studies of plasticity, we
      discuss the different forms of plasticity that are associated with cochlear
      implantation and we point to the interest of imaging studies for providing a
      prognosis of functional outcome after implantation.

PMID- 11847466
TI  - Sexual function and fertility in adult females and males with congenital adrenal
      hyperplasia.
AB  - Female patients with classic 21-hydroxylase deficiency (21-OHD) present with
      decreased fertility and low childbirth rates, women with a salt-wasting form of
      21-OHD being most severely affected. In cases of undersubstitution with
      glucocorticoids, tonic androgen secretion disturbs ovulation. However, even
      adequately substituted females may present with apparent infertility. Despite
      adrenal androgen suppression, adrenal progesterone secretion can prevent
      thickening of the endometrium in the follicular phase. Furthermore, functional
      ovarian hyperandrogenism is a common finding even in women with well-controlled
      classic 21-OHD. Psychosexual factors may also contribute significantly to
      decreased childbirth rates found in these patients. Genital ambiguity may lead to
      a disturbed body image and the patients have been found to feel less feminine
      than healthy control women. The repeated psychological insult caused by frequent
      genital examinations and operations is also important, though its exact impact
      has been difficult to determine. Finally, prenatal androgen excess can cause
      masculinization of the central nervous system leading to boyish behavior in
      childhood and decreased heterosexual activity in adulthood. Some recent reports
      show a high rate of infertility also in men with 21-OHD. They are at risk of
      benign testicular tumors, adrenal rests, which can lead to permanent infertility.
      Also, raised adrenal androgen production leading to increased estrogen
      concentrations can suppress gonadotropin secretion and may lead to a
      hypogonadotropic state.

PMID- 11847467
TI  - A new C-terminal located mutation (V272ter) in the PIT-1 gene manifesting with
      severe congenital hypothyroidism. Possible functionality of the PIT-1 C-terminus.
AB  - OBJECTIVE: We describe a newborn with clinical signs of severe hypothyroidism and
      combined pituitary hormone deficiency due to a new mutation in the PIT-1 gene.
      PATIENT AND METHODS: Endocrine stimulation test revealed a deficiency for PRL,
      TSH and GH, suggesting a defect in the pituitary transcription factor PIT-1.
      Genetic analysis of the PIT-1 gene was performed by exon-specific PCR, followed
      by SSCP mutation screening and DNA sequencing of the abnormal migrating
      fragments. RESULTS: DNA sequencing revealed a new mutation (V272ter) in direct
      neighborhood to a known mutational hot spot (R271W) in the C-terminal part of the
      PIT-1 molecule. CONCLUSIONS: Whereas the R271W mutation has a dominant negative
      effect on the mutant protein, the newly described mutation is inherited in an
      autosomal-recessive way. The biological consequences of these two different
      mutations are discussed.

PMID- 11847468
TI  - Prevalence of macroprolactin detected by Elecsys 2010.
AB  - BACKGROUND: Macroprolactin or big-big PRL is, usually, a complex of little
      prolactin (PRL) with anti-PRL autoantibody. There are some patients with
      hyperprolactinemia showing a high proportion of serum macroprolactin. However,
      its clinical significance is not clear. Immunoassays used to determine PRL differ
      in their ability to detect macroprolactin. Moreover, in recent years, PRL assays
      have changed from isotopic methods (radioimmunoassays and immunoradiometric
      assays) to non-isotopic automated immunoassays. The effect of macroprolactin on
      currently used methods is often unknown. The aim of this work was to study the
      different reactivity of macroprolactin in two immunoassays systems, Elecsys 2010
      and ACS Centaur, and to assess the clinical repercussion of this condition.
      METHODS: We studied retrospectively 956 consecutive routine patients. Samples
      with a PRL value >636 mIU/l (211 samples) were subjected to the polyethylene
      glycol (PEG) precipitation test to detect macroprolactin, and 2 of them also to
      gel filtration chromatography for further confirmation. PRL was measured by
      Elecsys 2010 and, alternatively, by ACS Centaur. RESULTS: By Elecsys 2010,
      macroprolactin was detected in 19 patients (9%). After removing macroprolactin,
      PRL levels were within the normal range in every case but one. When original sera
      from patients with macroprolactin were processed with ACS Centaur. PRL levels
      were normal or only marginally elevated. The correlation of PRL values in samples
      with and without macroprolactin assayed by both systems was 0.64 and 0.98,
      respectively. CONCLUSIONS: Nearly 9% of hyperprolactinemic patients detected by
      Elecsys 2010 may have macroprolactin, but the detection rate obtained using ACS
      Centaur is much lower. As macroprolactin seems to have minimal clinical
      relevance, it would be important that the users of PRL assays be aware to what
      extent macroprolactin interferes with their assays, and have available a
      validated method, such as the PEG precipitation test, to confirm the presence of
      macroprolactin.

PMID- 11847469
TI  - Measurements of urinary leptin and capillary leptin: alternative tools for the
      assessment of the leptin status?
AB  - OBJECTIVES: The aim of this study was to check whether leptin is reliably
      measurable in urine samples of children, adolescents, and adults and to examine
      whether capillary leptin measurements can be utilized as an alternative tool to
      assess the leptin status. METHODS: Two studies were performed. In both studies,
      leptin was quantified by an ultrasensitive and highly specific enzyme immunoassay
      (ELISA; R & D Systems). Anthropometric measures were taken from all study
      subjects, and body fat was calculated using skinfold thickness measurements. In
      study 1, leptin was analyzed in 24-hour urine samples of 155 healthy children and
      adolescents and 26 healthy adults after a methodological modification of the
      assay necessary for urine analysis. In study 2, venous and capillary blood
      samples were collected in 26 healthy adults within 10 min on the same day.
      RESULTS: After adapting the assay system to urine matrix, the detection range was
      20-160 pg/ml. Only in 2 of 181 urine samples reproducibly measurable urinary
      leptin concentrations in the lowest detection range were found. In study 2, a
      close correlation was found between log capillary and log venous leptin
      concentrations (r = 0.98, p < 0.001) and between log capillary as well as log
      venous leptin levels and percent body fat (r = 0.86, p < 0.001). CONCLUSIONS: Our
      results based on one of the most specific and sensitive ELISAs currently
      available show that leptin is generally undetectable in the urine from healthy
      children, adolescents and adults. Thus, urinary leptin excretion cannot be used
      as a noninvasive marker of the leptin status. Our findings in healthy adults show
      that the merely moderately invasive determination of capillary leptin allows a
      reliable assessment of the individual leptin status and may be used instead of
      venous leptin as a biochemical indicator of body fatness.

PMID- 11847470
TI  - Effects of estrogen on serum leptin levels and leptin mRNA expression in adipose
      tissue in rats.
AB  - OBJECTIVE: In this study, we examined changes in serum leptin levels during the
      estrus cycle and the role of estrogen in these changes. METHODS: We measured
      serum leptin levels during normal estrus cycles in intact rats and estradiol
      17beta (E2)-induced artificial estrus cycles in ovariectomized rats. RESULTS:
      Serum leptin levels increased 1.6-fold from 4.2 +/- 0.2 ng/ml during diestrus
      stage 2 to 6.7 +/- 0.9 ng/ml during proestrus stage during the 4-day estrus
      cycle. During the E2-induced estrus cycle, serum leptin levels increased 2.3-fold
      from 2.3 +/- 0.1 ng/ml at estrus to 5.4 +/- 1.2 ng/ml at proestrus. E2 also
      increased serum leptin concentrations and leptin mRNA expression in adipose
      tissue of immature rats. DISCUSSION: These findings suggest that increased serum
      leptin induced by estrogen during proestrus may trigger the preovulatory release
      of luteinizing hormone. Furthermore, our findings indicate that estrogen has a
      positive effect on leptin production in adipose tissue.

PMID- 11847471
TI  - Peripheral effects of PTH are not altered after thyroid surgery in euthyroid
      patients.
AB  - BACKGROUND: We have previously found decreased serum levels of both ionized
      calcium and 1,25(OH)2D and an increase in serum phosphate levels at 1 year after
      hemithyroidectomy. However, basal and stimulated parathyroid hormone (PTH)
      secretions were not altered. To investigate whether the observed biochemical
      changes after unilateral thyroid surgery may be due to a relative end-organ
      resistance to PTH, we studied the peripheral effects of infused hPTH-(1-34) in 6
      patients preoperatively and 3 months after hemithyroidectomy. METHODS: Serum
      levels of TSH, FT4 and FT3 were measured pre- and postoperatively. hPTH-(1-34)
      was infused at 0.9 IU/kg/h during 6 h. Blood samples for analysis of ionized
      calcium, intact PTH, phosphate, 25(OH)D, 1,25(OH)2D and urinary samples for
      calcium, phosphate and nephrogenous(n)-cAMP analysis were taken at baseline, when
      the infusion was discontinued after 6 h and at 24 h. RESULTS: Three months after
      hemithyroidectomy, serum levels of FT3 were decreased and TSH levels increased.
      Pre- and postoperative hPTH-(1-34) infusions induced increased serum levels of
      ionized calcium, 1,25(OH)2D, increased urinary excretion of phosphate and
      elevated n-cAMP levels. The changes in the studied biochemical variables during
      the hPTH-(1-34) infusions did not differ between the two study occasions.
      CONCLUSION: By using a 6-hour hPTH-(1-34) infusion protocol, we have shown that
      the peripheral PTH effect is not altered by a slight reduction in thyroid hormone
      levels at 3 months after hemithyroidectomy.

PMID- 11847472
TI  - Effects of growth hormone treatment on left ventricular dimensions in children
      with Noonan's syndrome.
AB  - OBJECTIVE: To study the effects of long-term growth hormone (GH) treatment on
      left ventricular (LV) dimensions in children with Noonan's syndrome (NS).
      METHODS: Echocardiographic measurements of LV dimensions were performed before
      and during GH treatment in 27 participants (21 boys, 6 girls) in a partly
      controlled 3-year trial of high-dose GH treatment (0.15 IU/kg/day). Nineteen
      children had a congenital heart defect, 1 of them had hypertrophic obstructive
      cardiomyopathy. In the first 3 years, the children were assigned to 1 of 2
      groups: group A with discontinuation of GH treatment in the 3rd year, or group B
      without GH treatment in the 1st year. After the 3rd year, 12 of the 27 children
      were followed up for 2 additional years to evaluate the long-term effects of GH
      treatment on the heart. RESULTS: At baseline, LV internal diameters were smaller,
      while posterior wall thickness were thicker than normal. Over the 1st year,
      changes in LV dimensions were comparable between the 2 groups. No significant
      differences were found in LV dimensions between the situation at baseline and
      after 4 years of GH treatment. CONCLUSION: Long-term high-dose GH treatment does
      not have clinically significant adverse effects on LV dimensions in children with
      NS.

PMID- 11847473
TI  - Growth hormone treatment does not alter lower limb asymmetry in children with
      Russell-Silver syndrome.
AB  - BACKGROUND: Growth hormone (GH) treatment has been proven to have a beneficial
      effect on growth in children with Russell-Silver syndrome (RSS). METHODS: We
      describe 7 prepubertal children with RSS and lower limb asymmetry treated with GH
      for 3 years. RESULTS: There was a significant increase in height without any
      significant change in the asymmetry. CONCLUSIONS: We conclude that the rapid
      growth acceleration to GH treatment does not alter the lower limb asymmetry in
      children with RSS.

PMID- 11847474
TI  - Diagnostic value of serum IGF-I and IGFBP-3 in growth hormone disorders in
      adults.
AB  - OBJECTIVE: To investigate the diagnostic value of serum insulin-like growth
      factor-I (IGF-I) and insulin-like growth factor-binding protein-3 (IGFBP-3)
      measurements in adult patients with acromegaly and GH deficiency (GHD). METHODS:
      Serum IGF-I and IGFBP-3 levels were measured in 39 active acromegalic patients,
      34 adult patients with GHD and 150 healthy adults. Disease activity in patients
      with acromegaly was confirmed by nadir GH levels during an oral glucose tolerance
      test (OGTT). Among patients with acromegaly, 15 had not been treated previously
      and 24 had been treated but not cured. GHD in adults was diagnosed by an insulin
      tolerance test (ITT). Among patients with GHD, 15 were aged 20-40 years (9 men
      and 6 women) and 19 were aged over 40 years (9 men and 10 women). One hundred and
      fifty healthy subjects were recruited as a control group. To compare the
      individual serum IGF-I and IGFBP-3 levels of patients with the results of the
      gold standard, we calculated age- and sex-corrected standard deviation scores
      (SDS) for individual IGF-I and IGFBP-3 levels. The sensitivities of serum IGF-I
      and IGFBP-3 measurements for the disease diagnosis were analyzed using the mean
      +/- 2 SD of the values of healthy control subjects as a diagnostic cutoff,
      defining 95% specificity. RESULTS: The mean IGF-I and IGFBP-3 SDS levels were
      significantly higher in active acromegalic patients, both untreated and treated
      but not cured, than in the control subjects (p < 0.05). The sensitivities of
      serum IGF-I and IGFBP-3 measurements for the diagnosis of acromegaly were 97.4
      and 81.8%, respectively. In untreated patients with acromegaly, the sensitivities
      of serum IGF-I and IGFBP-3 measurements for the diagnosis of disease were 100 and
      100%, while these were 95.8 and 72.7% in treated patients with acromegaly. In
      adult patients with GHD, the mean IGF-I and IGFBP-3 SDS were significantly lower
      than those of the control subjects (IGF-I, -2.2 +/- 0.8 vs. 0.0 +/- 1.0 SDS, p <
      0.0001); IGFBP-3, -1.7 +/- 1.2 vs. 0.0 +/- 1.0 SDS, p < 0.0001), but there was a
      considerable overlap between GHD in adults and the controls. In all patients with
      GHD, the sensitivities of serum IGF-I and IGFBP-3 measurements were 64.7 and
      52.9%, respectively. In the group of women aged 20-40 years, the sensitivity of
      IGF-I measurement for the diagnosis of GHD was 100%, although the number of
      patients was only 6. CONCLUSION: Both serum IGF-I and IGFBP-3 measurements are
      comparable to an oral glucose tolerance test in patients with untreated
      acromegaly, but in acromegalic patients that have undergone surgery and/or
      radiotherapy, serum IGF-I is more valuable for determining disease activity than
      serum IGFBP-3. Serum IGF-I and IGFBP-3 measurements are not valuable for the
      diagnosis of GHD in adults, but in women aged 20-40 years serum IGF-I measurement
      appears to be useful in the diagnosis of GHD.

PMID- 11847475
TI  - Unusual association of adrenal angiosarcoma and Cushing's disease.
AB  - The occurrence of an angiosarcoma in the adrenal gland is exceedingly rare as
      only 21 patients have been reported in the literature since its first description
      30 years ago. We report the clinicopathological features of a 34-year-old patient
      presenting with overt Cushing's syndrome due to a ACTH-secreting pituitary
      adenoma and an adrenal spindle cell angiosarcoma. This association made the
      diagnosis of Cushing's disease particularly puzzling in view of the results of
      biochemical tests which were compatible in part with adrenal and in part with
      paraneoplastic hypercortisolism and the negative pituitary imaging. The unique
      appearance of this tumor and its diagnostic implications are discussed.

PMID- 11847476
TI  - A case of pheochromocytoma with renal artery stenosis and post-surgical watery
      diarrhea.
AB  - A 35-year-old woman was admitted to our hospital with the following complaints,
      headache, sweating, anxiety, dizziness, nausea, vomiting and severe hypertension.
      The technical images (abdominal CT, scintigraphic octreotide scan and renal
      arteriography) revealed the presence of a left adrenal pheochromocytoma and
      stenosis of the renal artery. Ten days following adrenalectomy, watery diarrhea
      appeared. The long-acting somatostatin analogue octreotide (LAR, 30 mg/month,
      i.m.), was started, and after 2 weeks diarrhea decreased and gradually
      disappeared. In conclusion, we were confronted with an unusual case of
      pheochromocytoma associated with renal artery stenosis and the appearance of
      watery diarrhea some days after surgical treatment. Treatment with octreotide
      brought about the remission of diarrhea in this patient.

PMID- 11847478
TI  - Primary antiphospholipid syndrome: an unusual cause of adrenal insufficiency.
AB  - We describe a boy, 10 years and 5 months old, who developed acute adrenal gland
      insufficiency which was confirmed by hormonal investigation. Abdominal magnetic
      resonance imaging showed unilateral enlargement of the right adrenal gland,
      whereas the other gland seemed normal - no cause was apparent. Three months later
      the patient presented with thrombosis in the right femoral vein and in the veins
      of the right leg. Autoantibodies against cardiolipin were strongly positive,
      while antinuclear antibodies and antibodies against double-stranded
      deoxyribonucleic acid were absent. There was no evidence of antiphospholipid
      syndrome associated with drugs, connective tissue disorders, or malignancies,
      strongly suggesting the diagnosis of primary antiphospholipid syndrome. The
      development of adrenal insufficiency has been reported in primary
      antiphospholipid syndrome due to adrenal hemorrhage following vascular occlusion
      of adrenal vessels or secondary to anticoagulant therapy. It was interesting to
      note that in our patient adrenal gland insufficiency preceded other clinical
      evidence of the syndrome by 3 months. The primary antiphospholipid syndrome
      should be considered a possible cause of Addison's disease when the etiology is
      not obvious.

PMID- 11847477
TI  - Dehydroepiandrosterone sulfate treatment for atrichia pubis.
AB  - OBJECTIVE: To evaluate the efficacy of oral dehydroepiandrosterone sulfate
      (DHEAS) treatment for atrichia pubis in female adolescents. STUDY DESIGN: Two XY
      female adolescents with 17-hydroxylase deficiency and 2 XX females with
      panhypopituitarism presenting with atrichia pubis were treated with a daily
      dosage of DHEAS 10 mg/m2 body surface in addition to their regular substitution
      therapy. The dosage was increased according to clinical response. Pubic hair
      stages, growth and serum DHEAS were evaluated and in 1 case also serum IGFs and
      IGFBPs. RESULTS: A dosage of 10 mg/m2 for 1 year led to serum DHEAS levels at the
      lower limit of the normal range. 15 mg/m2 was needed to achieve pubic hair stage
      4-5 and axillary hair in patients with 17-hydroxylase deficiency. In
      panhypopituitarism, pubic hair developed at a slower pace and reached stage 4 on
      a dosage of 25-30 mg/m2. Baseline serum IGF-I SDS was -0.67 and did not change on
      the initial dosage of DHEAS, in combination with submaximal estrogen substitution
      (10 microg ethinyl estradiol). On the combination of 15 mg/m2 DHEAS and full
      estrogen substitution, IGF-I SDS increased to an average of -0.15. IGFBP-3 SDS
      increased from 1.4 to a mean of 2.6 in the first year, and went back to 1.4 in
      the second year. IGFBP-6 SDS was low at baseline (-2.5) and rose to -1.9 and -1.7
      IGF-II and IGFBP-1 showed an irregular pattern. CONCLUSIONS: Oral administration
      of DHEAS in a dosage of 15 mg/m2 o.d. is an efficacious treatment for atrichia
      pubis. For females with a panhypopituitarism a higher dosage appears needed.
      Given this and other biological actions of DHEAS, substitution therapy with DHEAS
      or DHEA to females with adrenal androgen deficiency appears rational.

PMID- 11847479
TI  - Tumor necrosis factor and motoneuronal degeneration: an open problem.
AB  - Tumor necrosis factor (TNF) has been implicated in the pathogenesis of various
      central nervous system diseases with an inflammatory component. Elevated TNF
      levels were observed in animal models of motor neuron disease (MND), and
      activation of the TNF system has been reported in patients with amyotrophic
      lateral sclerosis (ALS). The easy availability of scientific reports to the
      layman through the web, often based only on the abstracts, has prompted many
      patients to ask whether anti-TNF therapy might be beneficial in ALS. This review
      discusses the possible role of TNF in motoneuronal degeneration. Although TNF is
      mostly regarded as neurotoxic cytokine, there are reports of a neuroprotective
      and neurotrophic action. Studies with animal models of ALS are not sufficient to
      show whether TNF has a pathogenic or a protective role in MND though anti-TNF
      antibodies have shown protective effects in experimental allergic
      encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). On the other
      hand, while TNF-deficient mice are protected from EAE, anti-TNF antibodies worsen
      the disease in MS patients, suggesting caution in extrapolating preliminary basic
      studies to the patient.

PMID- 11847480
TI  - An age-related decline in interleukin-10 may contribute to the increased
      expression of interleukin-6 in brain of aged mice.
AB  - OBJECTIVES: The DNA-binding activity of nuclear factor kappaB (NFkappaB) is
      elevated in brain of aged mice, resulting in elevated levels of the inflammatory
      cytokine interleukin (IL)-6. The purpose of this study was to determine if in the
      brain of aged mice a decrease in the anti-inflammatory cytokine IL-10 contributes
      to the increase in IL-6. METHODS: In initial studies coronal brain sections and
      glial cells from adult (6-months-old) and aged (24-months-old) mice were
      incubated in the presence or absence of lipopolysaccharide (LPS) and the
      concentrations of IL-6 and IL-10 in supernatants were determined. In subsequent
      studies, the effect of recombinant murine IL-10 on constitutive and inducible
      NFkappaB activity, IL-6 mRNA expression and IL-6 protein secretion by glia
      cultured from brains of adult and aged mice was determined. RESULTS: Coronal
      brain sections and glia from aged mice secreted more IL-6 and less IL-10 than
      brain sections and glia from adults. This effect of age was evident in the
      absence and presence of LPS and suggested that a decrease in IL-10 production
      permitted increased IL-6 production. Consistent with this idea, treatment of glia
      from aged mice with recombinant IL-10 decreased both constitutive and inducible
      binding of NFkappaB to the IL-6 gene promoter. The decrease in NFkappaB activity
      was associated with a reduction of IL-6 mRNA and protein. Exogenous IL-10,
      however, had no effect on NFkappaB activity, which was undetectable in
      unstimulated glia from adult mice, and did not decrease steady-state levels of IL
      6 mRNA or IL-6 protein secretion. CONCLUSIONS: Collectively, these studies
      suggest that IL-10 constrained IL-6 gene expression in the adult brain, but in
      the aged brain it decreased and thus enabled a cascade of intracellular events
      that increased expression of the IL-6 gene.

PMID- 11847481
TI  - Impaired activity of phagocytic cells in Candida albicans infection after
      exposure to chronic varied stress.
AB  - OBJECTIVE: Candidiasis is a prototypic opportunistic fungal disease that may
      follow severe modulations of the immune system of the host. The purpose of this
      study was to evaluate which innate immune mechanisms involved in the protection
      against fungal invasion are impaired under stress conditions. METHODS: Wistar
      rats were infected intraperitoneally with Candida albicans and immediately
      exposed to chronic varied stress (CVS) over 10 days (CVS; Ca-S); the fungal
      burden (CFU), histopathological lesion and ACTH levels were evaluated.
      Additionally, functional assessment of peritoneal cells (PC) included the
      phagocytic and anticandidacidal activities and the production of H(2)O(2) and NO.
      RESULTS: In the only infected animals (Ca), C. albicans colonization stimulated
      an efficient inflammatory response, while in Ca-S rats poor tissue reactions were
      associated with increased CFU in livers and kidneys (p < 0.05, Ca vs. Ca-S).
      Whereas the phagocytic process was not modified, the candidacidal activity of PC
      was significantly decreased after the application of CVS (p < 0.001, Ca vs. Ca
      S). The H(2)O(2) production by macrophages and neutrophils was downregulated by
      the infection, and while at early intervals these cells possessed a residual
      oxidative capacity, by day 10, the production of this metabolite was blocked.
      Spontaneous NO production by macrophages was significantly increased in both Ca
      and Ca-S animals (p < 0.001), but in stressed rats, this reactive nitrogen
      intermediate was noticeably downregulated (p < 0.05, Ca vs. Ca-S). The
      hyperactivity of hypothalamus-pituitary-adrenal axis after exposure to stress was
      confirmed by an increase in baseline plasma ACTH levels. CONCLUSION: These
      results show that during infection with C. albicans, the exposure to CVS
      contributes to the spread of the fungus and downregulates critical functions of
      phagocytic cells involved in the control of this opportunistic pathogen.

PMID- 11847482
TI  - Influence of reduced nicotinamide adenine dinucleotide on the production of
      interleukin-6 by peripheral human blood leukocytes.
AB  - OBJECTIVE: Recently, therapy with nicotinamide adenine dinucleotide (NADH)
      revealed positive effects on neurodegenerative disorders associated with
      inflammation of the CNS, such as Parkinson's disease or Alzheimer's disease.
      Pathophysiologically, focal CNS inflammation seems to be accompanied by an
      unbalanced cytokine production, pointing to an involvement of the immune system.
      Therefore, the aim of our study was to investigate whether NADH could influence
      cytokine release of peripheral blood leukocytes (PBLs) with special reference to
      interleukin-6 (IL-6). METHODS: PBLs from 18 healthy donors were incubated in
      vitro with different concentrations of NADH to generate dose-response curves. As
      a control, mitogen-treated cells and unstimulated cells were included. RESULTS:
      In PBLs from the 18 healthy donors, NADH significantly stimulated the dose
      dependent release of IL-6, ranging from 6.25 to 400 microg/ml, compared to medium
      treated cells (p < 0.001). An amount of 1,000 pg/ml IL-6 was induced by NADH
      concentrations ranging from 3.1 to >25 microg/ml. CONCLUSIONS: It is concluded
      that NADH possesses cytokine-modulating effects on peripheral blood cells. The
      biological relevance of these data is discussed in the context of the recent use
      of NADH for the treatment of several neurodegenerative disorders.

PMID- 11847483
TI  - Plasma and cerebrospinal fluid interleukin-6 concentrations in posttraumatic
      stress disorder.
AB  - BACKGROUND: Interleukin-6 (IL-6) secretion is suppressed by glucocorticoids and
      stimulated by catecholamines. Patients with posttraumatic stress disorder (PTSD)
      have decreased cortisol and increased catecholamine secretion. The purpose of
      this study was to assess the relation of IL-6 levels and hypothalamic-pituitary
      adrenal and noradrenergic activity in patients with well-characterized PTSD.
      METHODS: Cerebrospinal fluid (CSF) was withdrawn via a lumbar subarachnoid
      catheter over 6 h from 11 combat veterans with PTSD and 8 age- and sex-matched
      healthy controls. Blood was withdrawn concurrently. We measured IL-6, CRH and
      norepinephrine concentrations in the CSF and IL-6, ACTH, cortisol and
      norepinephrine in plasma. RESULTS: Mean and median CSF IL-6 concentrations were
      higher in PTSD than in controls (mean = 24.0 vs. 14.6, p = 0.05; median = 26.7
      vs. 14.3, p < 0.03): plasma IL-6 concentrations, however, were not different
      between the two groups. Plasma IL-6 and norepinephrine were positively correlated
      in the PTSD group (r = +0.74, p < 0.04), but not in normals (r = -0.55, p =
      0.20). CONCLUSIONS: PTSD patients have increased CSF concentrations of IL-6.
      Their plasma IL-6 is not elevated but is more tightly associated with
      noradrenergic output in these patients than in normals. Both findings might be
      explained by the low cortisol secretion previously reported in PTSD as a result
      of lowered glucocorticoid suppression of IL-6 secretion. High levels of CSF IL-6
      may reflect neurodegeneration or compensatory neuroprotection.

PMID- 11847484
TI  - Functional asymmetry of thymus and the immune response in mice.
AB  - We have studied the capability of the mouse thymus for asymmetrical formation.
      Concanavalin A (Con A)-stimulated proliferation of thymocytes from the right and
      left lobes of the thymus appeared to be significantly different. The direction of
      the differences depends on the dominance of the brain hemispheres with regard to
      motor asymmetry. In mice with right-dominant hemispheres, thymocytes from the
      left lobe of the thymus demonstrate a higher level of Con A-stimulated
      proliferation than those from the right lobe. In mice with left-dominant
      hemispheres, we found the opposite dependence. The in vivo experiments showed
      that the properties of cells from the contralateral lobes of the thymus proved to
      be a deciding factor that defines the differences at the level of the immune
      response in recipient mice with left-dominant hemispheres. This effect was less
      pronounced in mice with right-dominant hemispheres. Further analysis showed that
      left and right-dominant hemisphere mice differ according to the immune response
      only if mice from both groups received cells from the left but not from the right
      lobe of the thymus. That is, in the formation of the immune response to sheep red
      blood cells, the functional asymmetry of both the brain and thymus is of great
      importance. The experiments show that brain hemispheres and cells from different
      lobes of the thymus are able to interact in the regulatory effect on the immune
      response. The injection of cells from the thymus lobe ipsilateral to the dominant
      hemisphere, results in a significant excess of the immune response in left
      dominant hemisphere mice in comparison with the response of right-dominant
      hemisphere mice. It can be concluded that this work demonstrates, for the first
      time, the asymmetrical function of a bilateral immune organ--the thymus. The
      asymmetry is shown not only at the level of Con A-induced proliferative activity
      but also at the level of the influence on the humoral T-dependent immune response
      in mice. Besides, we have found the interaction of brain hemispheres and thymus
      lobes in the regulation of the immune response.

PMID- 11847485
TI  - Physiological significance of the interleukin 1 receptor accessory protein.
AB  - Interleukin 1 receptor accessory protein (IL-1RAcP) is an essential signal
      transducing component of the IL-1 receptor type I. The recent availability of IL
      1RAcP-deficient (KO) mice allows to study the in vivo function of IL-1RAcP.
      Animals were injected intraperitoneally with rat recombinant IL-1beta (200
      ng/mouse), lipopolysaccharide (LPS, 5 microg/mouse), or subjected to 1-hour
      restraint stress. Neuroendocrine and immune parameters were measured 2 h after IL
      1 or LPS injection or just after restraint. In wild-type controls, IL-1 and LPS
      activated the hypothalamic-pituitary-adrenal axis and increased plasma IL-6. In
      KO mice, the plasma levels of corticosterone and IL-6 increased after LPS, but
      not after rat recombinant IL-1beta. The LPS-induced depression of the
      lymphoproliferation was similar in wild-type and KO mice. Finally, the 1-hour
      restraint was able to increase the plasma levels of corticosterone in KO mice.
      These results show that IL-1RAcP is essential for physiological activities of
      peripheral IL-1, as it was previously demonstrated for those of brain IL-1.
      However, using IL-1RAcP KO mice, we were unable to demonstrate a specific role of
      endogenous IL-1 during LPS-induced inflammation. Moreover, stress-induced
      activation of the hypothalamic-pituitary-adrenal axis may occur in the absence of
      the IL-1-transducing receptor, IL-1RAcP.

PMID- 11847486
TI  - Elevated levels of serum prolactin in patients with advanced multiple myeloma.
AB  - BACKGROUND AND OBJECTIVE: The role of prolactin in immunoregulation and normal
      hemopoiesis is well known. However, prolactin also seems to be involved in the
      pathomechanism of malignancies and autoimmune diseases. Elevated serum prolactin
      levels were reported in patients with malignant lymphoma, colon and breast
      carcinoma, systemic lupus erythematosus and rheumatoid arthritis. Recently we
      demonstrated prolactin immunostaining in bone marrow cells of patients with
      multiple myeloma. DESIGN AND METHODS: Serum prolactin levels of 56 patients with
      multiple myeloma, as well as serum beta(2)-microglobulin, and interleukin-6
      concentrations were determined in this study. RESULTS: Patients with advanced
      disease showed a significant increase in serum prolactin concentration, while
      patients with a clinical stage of I and II, and also control patients had normal
      values. The concentration of serum beta(2)-microglobulin and interleukin-6
      changed in parallel with that of serum prolactin in patients with multiple
      myeloma. Determining serum prolactin levels several times during the disease
      process in a given patient clearly showed that the prolactin concentration was
      increasing during the disease progression. INTERPRETATION AND CONCLUSIONS: Our
      results indicate a role of prolactin in disease progression in multiple myeloma.

PMID- 11847487
TI  - Panic attack as a marker of core psychopathological processes.
AB  - OBJECTIVE: The goal of this study is to test the hypothesis that panic attacks
      are a marker of core psychopathological processes across mental disorders and
      that there are distinct syndromal patterns of psychopathology associated with
      specific subtypes of panic attack that can be distinguished by age and associated
      fear at onset. METHODS: Data were drawn from the National Comorbidity Survey, a
      community-based household sample (n = 8,098) representative of the United States
      adult population. Four panic subtypes were identified based on findings from
      clinical studies and on our hypothesis. Multivariate logistic regression models
      were used to identify sociodemographic characteristics, panic symptoms and mental
      disorder correlates of each subtype. RESULTS: Results of multivariate logistic
      regression analyses identified distinct sociodemographic characteristics, panic
      symptoms, psychiatric comorbidity, suicidal behavior and use of services
      associated with early-onset and late-onset panic with and without
      fear/anticipatory anxiety at the first attack. CONCLUSIONS: These findings
      provide support for the hypothesis that panic attacks are a marker of core
      underlying psychopathological processes and introduce new, preliminary evidence
      to support the possible existence of different panic subtypes in the general
      population. While these results need replication, these findings suggest that the
      specific type of comorbidity among those with panic attacks can be predicted to a
      large degree by the age and associated fear/anticipatory anxiety at the onset of
      the panic attacks.

PMID- 11847488
TI  - Guilt and depression: a cross-cultural comparative study.
AB  - Although nearly a century has passed since Kraepelin's investigations in Java
      [Cbl Nervenheilk Psychiatr 1904; 27:468-469], one crucial question regarding
      guilt in the course of depression has still not been decided: Is there a more or
      less stable connection independent of culture, or is guilt confined to certain
      civilisations? This study investigated this issue in 100 Pakistani and 100
      Austrian out-patients diagnosed with 'major depression' according to DSM-IV by
      means of standardised instruments (Schedule for Affective Disorders and
      Schizophrenia-Life Time Version, Hamilton Rating Scale for Depression, 21-item
      version). The experiences of guilt were subdivided into ethical feelings (ethical
      anxiety and feelings of guilt) and delusions of guilt. It turned out that ethical
      feelings could be found in both cultures regardless of age and sex. They seem to
      be primarily related to the extent of depressive retardation. However, the
      distribution of the two subsets of ethical feelings was culture dependent.
      Delusions of guilt were confined to patients of the Austrian sample. So, our data
      qualify the exclusivity of the aforementioned two points of view and support the
      need for a psychopathologically differentiated approach.

PMID- 11847490
TI  - Concordance of acute and transient psychoses and cycloid psychoses.
AB  - OBJECTIVE: We prospectively investigated a sample of 42 patients with acute and
      transient psychotic disorder (ATPD) as defined by the 10th revision of the
      International Classification of Diseases (ICD-10; F23) to determine the clinical
      and demographic features of this entity and its relationship to cycloid
      psychoses. METHODS: During a 5-year period, all in-patients with ATPD were
      identified. We systematically evaluated demographic and clinical features and
      carried out follow-up investigations on average 2 years after the index episode,
      using standardised instruments. RESULTS: We found 42 cases of ATPD (4.1%) among
      1,036 patients treated for psychotic disorders or a major affective episode.
      There was a marked female preponderance in ATPD (79%). Fifty-five percent of
      cases concurrently met the criteria of cycloid psychosis according to Perris and
      Brockington [in Perris C, Struwe G, Jansson B (eds): Biological Psychiatry.
      Amsterdam, Elsevier, 1981, pp 447-450]. There was no difference in gender
      distribution between cycloid and non-cycloid ATPD. As expected, abrupt onset and
      polymorphic features were significantly more common in cycloid than in non-
      cycloid ATPD. At follow-up, patients with cycloid ATPD showed less persistent
      alterations and better social functioning. CONCLUSION: ATPD as defined by ICD-10
      is a heterogeneous category. A diagnosis of cycloid psychosis is made in half of
      the cases of ATPD, and in these cases, the prognosis is more favourable.

PMID- 11847489
TI  - The delusions of Capgras and intermetamorphosis in a patient with right
      hemisphere white-matter pathology.
AB  - Previous neuropsychological studies have demonstrated an association between
      person misidentification and right-hemisphere dysfunction. In the study reported
      here, we explore the contribution of facial and visual recognition impairments in
      a patient with right-hemisphere subcortical white-matter pathology in the frontal
      and parietal lobes and a diagnosis of vascular cognitive impairment. The patient
      displayed false recognition of unfamiliar faces and deficient retrieval of key
      biographic detail for famous faces. These results are discussed in the context of
      the contribution of deficiencies in the visual system and subcortical white
      matter lesions to the development of Capgras delusion.

PMID- 11847491
TI  - Recurrent unipolar mania in a psychiatric hospital setting in the Fiji Islands.
AB  - This study aimed to determine the rate of unipolar mania and compare its
      characteristics with those of other bipolar affective disorders in a psychiatric
      hospital in the Fiji Islands. Fifty-one patients with unipolar mania seen between
      January 1999 and October 2000, had their diagnosis confirmed using the Schedules
      for Clinical Assessment in Neuropsychiatry and the International Classification
      of Diseases, 10th edition. Their demographic and clinical characteristics were
      compared with those of 31 manic-depressive patients seen during the period under
      review. Unipolar mania constituted 47.2% of the bipolar affective disorders in
      this sample. The frequency of episodes, duration of affective illness, mean age
      at onset, gender distribution, marital status, employment status and race were
      not significantly different for the unipolar manic and manic-depressive groups (p
      > 0.05). Family history of major psychiatric morbidity was 9.8% for the unipolar
      manic patients and 22.6% for the manic-depressive group (p > 0.05). Recurrent
      unipolar mania may be considered a useful category based on its high rate,
      although its demographic and clinical characteristics do not clearly distinguish
      it from manic-depression.

PMID- 11847492
TI  - Stability of memories of parental rearing among psychiatric inpatients: a
      replication based on EMBU subscales.
AB  - With regard to information about parental rearing, retrospective data are
      exclusively available among adults. These data are vulnerable due to various
      biases. This study was performed in order to replicate the findings of overall
      stability of three perceived parental rearing factors of the EMBU (Swedish
      acronym for 'own memories of childhood upbringing') based on 14 rather detailed
      subscales. A consecutive sample of 220 depressive inpatients were investigated on
      admission and at discharge by means of the EMBU, the Beck Depression Inventory
      and the Dysfunctional Attitude Scale. Perceived parental rearing scores showed
      high stability despite clinically significant changes in the severity of
      depression, except for 'tolerance', 'guilt engendering', 'performance
      orientation' and 'shaming' parenting with probable gender-specific effects which
      were found to covary with dysfunctional attitudes. Recall of parenting should be
      taken as a subjective truth when it is assessed by standardised behaviour
      oriented questionnaires like the EMBU.

PMID- 11847493
TI  - ICD-10 mild cognitive disorder following meningitis due to neurosarcoidosis.
AB  - We report the case of a patient referred to our department with the diagnosis of
      conversion disorder, who ultimately proved to have neurosarcoidosis presenting
      with mild cognitive disorder. Despite the criticism of mild cognitive disorder as
      a diagnostic entity, our patient met the criteria for it. The reported case
      exemplifies the difficulties in classifying mild cognitive deficits in patients
      suffering from brain diseases without major morphological damage.

PMID- 11847494
TI  - The suffering of hypersocial patients.

PMID- 11847498
TI  - Magnetic resonance of metabolic and degenerative diseases in children.
AB  - Cerebral magnetic resonance imaging and spectroscopy form an integral part in the
      diagnosis and management of the vast spectrum of metabolic and degenerative
      disorders in children. These varied disorders have been classified in many
      different ways, according to anatomic location, head size, enzyme disorder, or
      cellular morphology and function. The clinical features and magnetic resonance
      imaging appearances of the most common disorders are discussed.

PMID- 11847499
TI  - Magnetic resonance imaging in pediatric stroke.
AB  - Pediatric stroke is a term that can be used to encompass everything from hypoxic
      ischemic injury to the fetal central nervous system, and especially the premature
      neonate, to bland versus hemorrhagic infarction from arterial or venous causes in
      the infant and older child. Pediatric stroke is a chronically underrecognized and
      therefore underdiagnosed problem that may have significant economic implications.
      The risk factors for stroke in children are numerous and differ from those in
      adults. However, with adequate workup, the etiology can be identified in about
      75% of cases. Cardiac disorders and hemoglobinopathy are the most common causes
      of ischemic infarction in children, whereas various congenital anomalies of the
      blood vessels or defects in coagulation or platelet function often are found in
      children with parenchymal hemorrhage. Magnetic resonance imaging provides a
      noninvasive method of investigating childhood stroke, aiding in both better
      diagnosis and management of this problem.

PMID- 11847500
TI  - Magnetic resonance imaging in pediatric epilepsy.

PMID- 11847501
TI  - Pediatric functional magnetic resonance imaging: progress and challenges.
AB  - Functional magnetic resonance imaging (fMRI) in the pediatric population promises
      to provide novel insights into the nature of both normal and abnormal functional
      brain development as well as changes in brain function due to various
      interventions. Although acquisition of fMRI data from children is associated with
      a number of methodological challenges, primarily compliance and head motion, good
      quality data can be obtained. For example, conditioning and personal interactions
      can improve compliance, and motion reduction techniques can successfully reduce
      artifacts due to head motion. Analysis of pediatric fMRI data also involves
      challenges regarding spatial normalization and characterization of the
      hemodynamic response across development. Substantial progress has been made in
      understanding cognitive function and developmental disorders in children, but
      attention to the methodological issues raised in this review and continued
      investigations in this area are expected to result in further progress.

PMID- 11847502
TI  - Video-assisted endoscopic endocrine neck surgery with a benefit of cosmesis: a
      new technique using a totally gasless anterior neck skin lifting method.

PMID- 11847503
TI  - [Sicilian gambit; a new strategy for antiarrhythmic therapy].

PMID- 11847504
TI  - Effect of L-canavanine, an Inhibitor of inducible nitric oxide synthase, on
      myocardial dysfunction during septic shock.
AB  - Overproduction of nitric oxide (NO) by inducible NO synthase (iNOS) plays a role
      in the pathophysiology of septic shock. The depression of cardiac contractility
      in such situations is mediated by proinflammatory cytokines, including
      interleukin-1beta (IL-1beta), and tumor necrosis factor-alpha (TNF-alpha). The
      effects of two NOS inhibitors with different isoform selectivity were compared in
      isolated working rat hearts. The depression of contractility by IL-1beta and TNF
      alpha was prevented by administration of a nonselective nitric oxide synthase
      inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME) or an inhibitor of
      inducible nitric oxide synthase, L-canavanine. In contrast, when L-NAME was
      administered in the absence of IL-1beta and TNF-alpha, it depressed contractility
      over the 2h perfusion period by significantly reducing coronary flow. These
      results support current thinking that the depression of myocardial function by IL
      1beta and TNF-alpha is mediated, at least in part, by an intracardiac increase in
      inducible nitric oxide synthase, and that in contrast to L-NAME, the decline in
      coronary conductance seen in cytokine-treated is not prevented by L-canavanine
      hearts. L-canavanine shows selective inhibition of inducible nitric oxide
      synthase unlike the vasopressor action of L-NAME in cytokine-treated hearts.

PMID- 11847505
TI  - Current perception threshold increases during pregnancy but does not change
      across menstrual cycle.
AB  - It is well known that pregnancy reduces anesthetic requirements in response to
      various noxious stimuli. However, there have been no detailed reports concerning
      functional changes in nerve fibers during pregnancy. Using a Neurometer, a
      recently available commercial quantitative sensory monitor, we measured current
      perception threshold (CPT) values for three frequencies corresponding to the
      stimulation of A-beta, A-delta and C fibers on the median nerve in women at
      several stages: late pregnancy, the follicular phase and the luteal phase. A
      significant difference in CPT values on A fibers was noted between the gravid and
      the nongravid women, but, no significant difference in CPT values was noted in
      any of the nongravid women in the follicular or luteal phases. Our results
      support the current theory that pregnancy changes nerve fiber conduction, as
      indicated by an increase in CPT values especially on myelinated fibers, but does
      not cause changes in CPT values across the menstrual cycle.

PMID- 11847506
TI  - Breast-conserving therapy in the management of early stage breast cancer: Our
      experience in 103 cases.
AB  - PURPOSE: The aim of this study is to determine whether our results in
      breastconserving therapy of 103 patients with earlystage breast cancer are
      comparable to those of other facilities or not. MATERIALS AND METHODS: From
      January 1990 to October 1999, 103 patients with earlystage breast cancer were
      treated by breastconserving surgery and whole breast irradiation. All patients
      were of Stages I or II, and the greatest dimensions of primary tumor were less
      than 3 cm. The median followup time was 47 months from the completion of
      postoperative radiotherapy. Local, regional and distant failure rates, and
      survival rate were presumed using the KaplanMeyer method. RESULTS: One patient
      suffered from local recurrence 30 months later. She was followed by simple
      mastectomy and kept from further recurrence. No regional relapse occurred.
      Distant metastases were seen in three patients:two patients in bones, and one
      patient in a bone and the liver after 19, 35, and 32 months, respectively. One
      patient died from disseminated cancer in 41 months. Only one patient died due to
      intercurrent disease. Both 5year and 10year diseasefree survival rates were
      94.2%, and both 5year and 10year causespecific survival rates were 98.3%.
      CONCLUSION: Our results were comparable to previously reported data. In this
      stage although the followup time was too short to define the longterm outcome, it
      suggested that breast conserving therapy was acceptable and effective in the
      management of earlystage breast cancer.

PMID- 11847508
TI  - Primary ovarian tumor undergoing surgical management during pregnancy.
AB  - The aim of this study was to evaluate the preoperative symptoms of patients with
      primary ovarian tumors undergoing surgery during pregnancy and non-pregnancy. We
      retrospectively analyzed the medical records of 71 pregnant patients who
      underwent surgery for primary ovarian tumors (pregnant) and 580 non-pregnant
      patients (non-pregnant) aged 15similar44 years old. In the non-pregnant group,
      79.7% of the patients complained of abdominal pain at the first examination.
      However, in the pregnant group, 62.0% of the patients reported no symptoms and
      31.0% of them reported abdominal pain (p<0.05). There were no significant
      differences in the percentage of ovarian malignancies between the two groups
      (8.5% vs. 6.6%). However, the incidence of the advanced stage of greater-than-or
      equal Ic in ovarian malignancies in the non-pregnant group was 42.1%, while it
      was 0% (p<0.05) in the pregnant group. Ovarian tumors including ovarian
      malignancies were significantly more frequently diagnosed with no symptoms in the
      pregnant group than in the non-pregnant group.

PMID- 11847507
TI  - Relation of apolipoprotein (a) phenotypes to diabetic retinopathy in elderly type
      2 diabetes.
AB  - The aim of this study was to clarify the relationship between apolipoprotein (a)
      (apo (a) ) phenotypes and diabetic retinopathy in elderly type 2 diabetes. Serum
      Lp (a) concentrations and apo (a) phenotypes were analyzed in 250 diabetic
      patients aged 60 to 88 years old. Apo (a) phenotypes were classified into 7
      subtypes (F, B, S1, S2, S3, S4, O (Null) ) by the method SDS electrophoresis with
      Western blotting. Patients were divided into two groups according to their apo
      (a) phenotypes:a low molecular weight (LMW) Lp (a) group, and a high molecular
      weight (HML) Lp (a) group. Patients were classified as having one of 4 types of
      diabetic retinopathy: no retinopathy (R0), simple retinopathy (R1), pre
      proliferative retinopathy (R2), and proliferative retinopathy (R3). There was a
      significant association between serum Lp (a) levels and severity of diabetic
      retinopathy (p<0.001). A gradual trend toward increasing serum Lp (a) levels was
      observed across the groups (from R0 to R3). A significantly greater percentage of
      LMW Lp (a) was observed in the R1, R2, and R3 groups than in the R0 group (42.9%
      (p<0.001), 27.0% (p<0.01), and 27.3% (p<0.05) vs. 10.4%). Multiple logistic
      regression analysis revealed that duration of diabetes and LMW Lp (a) are
      independent risk factors for diabetic retinopathy. These results provide
      significant evidence that LMW Lp (a) contributes to an increased risk of diabetic
      retinopathy in elderly type 2 diabetes.

PMID- 11847509
TI  - [The appearance manner of C-response in healthy individuals].
AB  - The existence of long-latency responses following M and H waves in the complex
      muscular action potential elicited by stimulation of peripheral nerves was
      reported by Upton et al. This electrical potential, called the C-response, is
      applied to examinations in central nervous system diseases. However, the pathway
      and details on fundamental types of waveforms have not yet been clarified. The
      main purpose of this study is to classify the waveforms of the C-response, based
      on the analysis of waveforms. To investigate the type of C-responses, we
      developed a modified superimposing method. We also investigated the types in
      different age groups. Fifty-seven healthy individuals (30 males and 27 females)
      aged between 20 and 73 (average age: 43.1 years old) were enrolled as subjects.
      All subjects were instructed to oppose the thumb against the little finger of
      their dominant hands so that the abductor pollicis brevis was in voluntary
      isometric contraction; subsequently, electrical stimuli were repeatedly applied
      to the median nerve at the wrist. The stimuli had a strength of 110% of the
      threshold value of the M wave. The electrical potential was recorded with surface
      electrodes placed on the muscle belly of the abductor pollicis brevis. In each
      measurement, 200 waveforms were averaged. A Neuropack 8 (Nihon Kohden, Co., Ltd.)
      was used for recording and analysis of electromyograms. Measured negative peak
      latencies (ms) were divided by the subjects' heights (m) to obtaining the
      corrected latencies per unit height. The time axis of a waveform was also
      corrected with each height, and shifted so that the latency of the negative peak
      of the H wave was observed at the same position (modified superimposing method).
      Then, the position where the negative peak of the C-response appeared most
      frequently was examined. We clarified that C-responses have three types. C
      responses have two major negative peaks basically, C1 and C2 (the latency of C1
      is shorter than that of C2). Type 1 has only C2; Type 2 has C1 and C2; Type 3 has
      both C1 and C2 but the latency of C2 is shorter than that of Type 2. Type 1 was
      observed in 37 cases (64.9%), Type 2 in 15 cases (26.3%), and Type 3 in 5 cases
      (8.8%). The incidence of each C-response type depended on the age of the
      subjects, Type 1 was observed frequently in young subjects, and Types 2 and 3
      were observed more frequently as the age of the subjects increased.

PMID- 11847510
TI  - Surgical endovascular stent grafting for a ruptured penetrating atherosclerotic
      ulcer of the aortic arch.
AB  - Penetrating atherosclerotic ulcer (PAU) is defined as an atherosclerotic lesion
      in which an ulceration occurs in the diseased aortic intima leading to disruption
      of the internal elastic lamina. It may cause a pseudoaneurysm formation or
      transmural aortic rupture. We describe a patient in whom a ruptured PAU in the
      distal aortic arch was treated successfully by a surgical endovascular stent
      graft. Through a median sternotomy and under deep hypothermic circulatory arrest,
      the aorta was transected between the left common carotid and subclavian arteries.
      A dacron prosthetic graft with self-expanding original Z type stents attached
      inside of the distal half was inserted through the aortotomy to exclude the PAU.
      By performing the procedure through a median sternotomy, we could eliminate
      dissection around the ruptured aortic wall. The stented graft was secured safely
      in the thoracic aorta to exclude the ruptured ulceration located distal to the
      left subclavian artery. PAU should be recognized widely as a distinct
      cardiovascular surgical problem which may lead to intramural hematoma with or
      without dissection or rupture.

PMID- 11847511
TI  - Effect of maclorides on duration and resolution of symptoms and complication of
      pneumonia in children with influenza.
AB  - We randomly administered cephalosporins or macrolides to 365 pediatric patients
      with influenza-like symptoms and compared the clinical course and complication
      rate of pneumonia. One hundred and fifty-four patients received cephalosporins
      (Group 1) and 211 received macrolides (Group 2). There were no significant
      differences in age, male/female ratio and body weight between the two groups.
      Macrolides alleviated fever significantly faster than cephalospoins (3.8plus
      minus 1.4 days vs 4.3plus minus 1.4 days), though maximum body temperature showed
      no significant difference between the two groups. Thirty-nine patients underwent
      laboratory examinations and twenty-nine had high influenza A (H3N2) virus
      haemagglutinate inhibition (HI) titer, six had high influenza B (B1) virus HI
      titer and four did not show any elevation of influenza virus HI titer. Thirteen
      patients in Group 1 and two patients in Group 2 suffered from pneumonia and the
      complication rate was significantly lower in Group 1 than in Group 2 (8.4% vs
      0.9%). All of them recovered within two weeks and did not have any other
      complications. CONCLUSION: Macrolides are more effective in reducing the time
      required to alleviate fever and complication rate of pneumonia than
      cepharosporines in children with influenza and influenza-like illness. These
      results indicate that macrolides may have therapeutic value for influenza virus
      infection.

PMID- 11847512
TI  - A case of dumbbell tumor of the superior mediastinum removed by combined
      thoracoscopic surgery.
AB  - We report a case of a neurogenic dumbbell tumor in the superior mediastinum
      resected completely by the combined application of thoracoscopy and neurosurgery
      performed by an orthopedic surgeon. A 54-year-old female was admitted because her
      chest X-ray showed a superior mediastinal mass. Computed tomography and magnetic
      resonance imaging revealed that the tumor was extradural dumbbell-shaped and
      compressed the spinal cord through the intervertebral foramen between Th2 and
      Th3. First, she underwent laminectomy of the vertebrae (Th1similarTh3) and
      separation of the tumor from the dura mater and the root of the second left
      intercostal nerve in the right semilateral position. Then in the same position,
      three thoracic ports were placed and the tumor was resected completely using
      thoracoscopy in a one-stage operation. The pathological diagnosis was
      neurilemmoma. There has been no sign of serious neurologic deficits or of
      recurrence four years after the operation. Thus, the procedure is a minimally
      invasive approach, which is both safe and useful.

PMID- 11847513
TI  - [Diagnosis and treatment of severe acute pancreatitis].

PMID- 11847514
TI  - [Helicobacter Pylori gastritis with reference to its diagnosis, eradication and
      post-eradication outcome].

PMID- 11847515
TI  - [A 11-year-old girl with metagonimus Yokogawai infection and prolonged abdominal
      pain].

PMID- 11847517
TI  - Adenylyl cyclase types I and VI but not II and V are selectively inhibited by
      nitric oxide.
AB  - Adenylyl cyclase (AC) isoforms catalyze the synthesis of 3',5'-cyclic AMP from
      ATP. These isoforms are critically involved in the regulation of gene
      transcription, metabolism, and ion channel activity among others. Nitric oxide
      (NO) is a gaseous product whose synthesis from L-arginine is catalyzed by the
      enzyme NO synthase. It has been well established that NO activates the enzyme
      guanylyl cyclase, but little has been reported on the effects of NO on other
      important second messengers, such as AC. In the present study, the effects of
      sodium nitroprusside (SNP), a nitric oxide-releasing compound, on COS-7 cells
      transfected with plasmids containing AC types I, II, V and VI were evaluated.
      Total inhibition (approximately 98.5%) of cAMP production was observed in COS-7
      cells transfected with the AC I isoform and previously treated with SNP (10 mM)
      for 30 min, when stimulated with ionomycin. A high inhibition (approximately 76%)
      of cAMP production was also observed in COS-7 cells transfected with the AC VI
      isoform and previously treated with SNP (10 mM) for 30 min, when stimulated with
      forskolin. No effect on cAMP production was observed in cells transfected with AC
      isoforms II and V.

PMID- 11847516
TI  - Proteinase activity regulation by glycosaminoglycans.
AB  - There are few reports concerning the biological role and the mechanisms of
      interaction between proteinases and carbohydrates other than those involved in
      clotting. It has been shown that the interplay of enzymes and glycosaminoglycans
      is able to modulate the activity of different proteases and also to affect their
      structures. From the large number of proteases belonging to the well-known
      protease families and also the variety of carbohydrates described as widely
      distributed, only few events have been analyzed more deeply. The term "family" is
      used to describe a group of proteases in which every member shows an evolutionary
      relationship to at least one other protease. This relationship may be evident
      throughout the entire sequence, or at least in that part of the sequence
      responsible for catalytic activity. The majority of proteases belong to the
      serine, cysteine, aspartic or metalloprotease families. By considering the
      existing limited proteolysis process, in addition to the initial idea that the
      proteinases participate only in digestive processes, it is possible to conclude
      that the function of the enzymes is strictly limited to the cleavage of intended
      substrates since the destruction of functional proteins would result in normal
      tissue damage. In addition, the location as well as the eventual regulation of
      protease activity promoted by glycosaminoglycans can play an essential role in
      the development of several physiopathological conditions.

PMID- 11847518
TI  - Microsatellite instability and cytogenetic survey in myeloid leukemias.
AB  - Microsatellites are short tandem repeat sequences dispersed throughout the
      genome. Their instability at multiple genetic loci may result from mismatch
      repair errors and it occurs in hereditary nonpolyposis colorectal cancer. This
      instability is also found in many sporadic cancers. In order to evaluate the
      importance of this process in myeloid leukemias, we studied five loci in
      different chromosomes of 43 patients, 22 with chronic myelocytic leukemia (CML)
      in the chronic phase, 7 with CML in blast crisis, and 14 with acute myeloid
      leukemia (AML), by comparing leukemic DNA extracted from bone marrow and
      constitutional DNA obtained from buccal epithelial cells. Only one of the 43
      patients (2.1%), with relapsed AML, showed an alteration in the allele length at
      a single locus. Cytogenetic analysis was performed in order to improve the
      characterization of leukemic subtypes and to determine if specific chromosome
      aberrations were associated with the presence of microsatellite instability.
      Several chromosome aberrations were observed, most of them detected at diagnosis
      and during follow-up of the patients, according to current literature. These
      findings suggest that microsatellite instability is an infrequent genetic event
      in myeloid leukemias, adding support to the current view that the mechanisms of
      genomic instability in solid tumors differ from those observed in leukemias,
      where specific chromosome aberrations seem to play a major role.

PMID- 11847519
TI  - Butyrate induces apoptosis in murine macrophages via caspase-3, but independent
      of autocrine synthesis of tumor necrosis factor and nitric oxide.
AB  - We demonstrated that 4 mM butyrate induces apoptosis in murine peritoneal
      macrophages in a dose- and time-dependent manner as indicated by studies of cell
      viability, flow cytometric analysis of annexin-V binding, DNA ladder pattern and
      the determination of hypodiploid DNA content. The activity of caspase-3 was
      enhanced during macrophage apoptosis induced by butyrate and the caspase
      inhibitor z-VAD-FMK (100 microM) inhibited the butyrate effect, indicating the
      major role of the caspase cascade in the process. The levels of butyrate-induced
      apoptosis in macrophages were enhanced by co-treatment with 1 microg/ml bacterial
      lipopolysaccharide (LPS). However, our data indicate that apoptosis induced by
      butyrate and LPS involves different mechanisms. Thus, LPS-induced apoptosis was
      only observed when macrophages were primed with IFN-gamma and was partially
      dependent on iNOS, TNFR1 and IRF-1 functions as determined in experiments
      employing macrophages from various knockout mice. In contrast, butyrate-induced
      macrophage apoptosis was highly independent of IFN-gamma priming and of iNOS,
      TNFR1 and IRF-1 functions.

PMID- 11847520
TI  - PCR-based ribotyping of Staphylococcus aureus.
AB  - Genotyping techniques are valuable tools for the epidemiologic study of
      Staphylococcus aureus infections in the hospital setting. Pulsed-field gel
      electrophoresis (PFGE) is the current method of choice for S. aureus strain
      typing. However, the method is laborious and requires expensive equipment. In the
      present study, we evaluated the natural polymorphism of the genomic 16S-23S rRNA
      region for genotyping purpose, by PCR-based ribotyping. Three primer pairs were
      tested to determine the size of amplicons produced and to obtain better
      discrimination with agar gel electrophoresis and ethidium bromide staining. The
      resolution of the typing system was determined using sets of bacteria obtained
      from clinical specimens from a large tertiary care hospital. These included DNA
      from three samples obtained from a bacteremic patient, six strains with known and
      diverse PGFE patterns, and 88 strains collected over a 3-month period in the same
      hospital. Amplification patterns obtained from samples from the same patient were
      identical, and PFGE from samples known to be different produced three genotypes.
      Amplification of DNA from 61 methicillin-resistant isolates produced only one
      pattern. Methicillin-sensitive strains yielded a diversity of patterns, pointing
      to a true polyclonal distribution throughout the hospital (22 unique patterns
      from 27 strains). Computer-based software can be used to differentiate among
      identifiable strains, given the low number of bands and good characterization of
      PCR products. PCR-based ribotyping can be a useful technique for genotyping
      methicillin-sensitive S. aureus strains, but is of limited value for methicillin
      resistant strains.

PMID- 11847521
TI  - Effects of lipopolysaccharide on low- and high-density cultured rabbit vascular
      smooth muscle cells: differential modulation of nitric oxide release, ERK1/ERK2
      MAP kinase activity, protein tyrosine phosphatase activity, and DNA synthesis.
AB  - Previous studies have shown that exogenously generated nitric oxide (NO) inhibits
      smooth muscle cell proliferation. In the present study, we stimulated rabbit
      vascular smooth muscle cells (RVSMC) with E. coli lipopolysaccharide (LPS), a
      known inducer of NO synthase transcription, and established a connection between
      endogenous NO, phosphorylation/dephosphorylation-mediated signaling pathways, and
      DNA synthesis. Non-confluent RVSMC were cultured with 0, 5, 10, or 100 ng/ml of
      the endotoxin. NO release was increased by 86.6% (maximum effect) in low-density
      cell cultures stimulated with 10 ng/ml LPS as compared to non-stimulated
      controls. Conversely, LPS (5 to 100 ng/ml) did not lead to enhanced NO production
      in multilayered (high density) RVSMC. DNA synthesis measured by thymidine
      incorporation showed that LPS was mitogenic only to non-confluent RVSMC;
      furthermore, the effect was prevented statistically by aminoguanidine (AG), a
      potent inhibitor of the inducible NO synthase, and oxyhemoglobin, an NO
      scavenger. Finally, there was a cell density-dependent LPS effect on protein
      tyrosine phosphatase (PTP) and ERK1/ERK2 mitogen-activated protein (MAP) kinase
      activities. Short-term transient stimulation of ERK1/ERK2 MAP kinases was maximal
      at 12 min in non-confluent RVSMC and was prevented by preincubation with AG,
      whereas PTP activities were inhibited in these cells after 24-h LPS stimulation.
      Conversely, no significant LPS-mediated changes in kinase or phosphatase
      activities were observed in high-density cells. LPS-induced NO generation by
      RVSMC may switch on a cell density-dependent proliferative signaling cascade,
      which involves the participation of PTP and the ERK1/ERK2 MAP kinases.

PMID- 11847522
TI  - Ventilation with high tidal volume induces inflammatory lung injury.
AB  - Mechanical ventilation with high tidal volumes (V(T)) has been shown to induce
      lung injury. We examined the hypothesis that this procedure induces lung injury
      with inflammatory features. Anesthetized male Wistar rats were randomized into
      three groups: group 1 (N = 12): V(T) = 7 ml/kg, respiratory rate (RR) = 50
      breaths/min; group 2 (N = 10): V(T) = 21 ml/kg, RR = 16 breaths/min; group 3 (N =
      11): V(T) = 42 ml/kg, RR = 8 breaths/min. The animals were ventilated with
      fraction of inspired oxygen of 1 and positive end-expiratory pressure of 2 cmH2O.
      After 4 h of ventilation, group 3, compared to groups 1 and 2, had lower PaO2
      [280 (range 73-458) vs 517 (range 307-596), and 547 mmHg (range 330-662),
      respectively, P<0.05], higher wet lung weight [3.62 +/- 0.91 vs 1.69 +/- 0.48 and
      1.44 +/- 0.20 g, respectively, P<0.05], and higher wet lung weight/dry lung
      weight ratio [18.14 (range 11.55-26.31) vs 7.80 (range 4.79-12.18), and 6.34
      (range 5.92-7.04), respectively, P<0.05]. Total cell and neutrophil counts were
      higher in group 3 compared to groups 1 and 2 (P<0.05), as were baseline TNF-alpha
      concentrations [134 (range <10-386) vs 16 (range <10-24), and 17 pg/ml (range <10
      23), respectively, P<0.05]. Serum TNF-alpha concentrations reached a higher level
      in group 3, but without statistical significance. These results suggest that
      mechanical ventilation with high V T induces lung injury with inflammatory
      characteristics. This ventilatory strategy can affect the release of TNF-alpha in
      the lungs and can reach the systemic circulation, a finding that may have
      relevance for the development of a systemic inflammatory response.

PMID- 11847523
TI  - Lamivudine therapy for hepatitis B in renal transplantation.
AB  - Antiviral therapies are associated with an increased risk of acute rejection in
      transplant patients. The aim of the present study was to evaluate the efficacy
      and safety of lamivudine therapy for hepatitis B virus (HBV) infection in renal
      transplant patients. Six patients were included in this study. They received 150
      mg/day of lamivudine during a follow-up period of 24 months. The laboratory tests
      monitored were HBV DNA, HBsAg, HBeAg, ALT, gamma-GT, serum creatinine and blood
      cyclosporine levels. The HBV DNA became undetectable in four patients as early as
      in the third month of treatment. After six months, the viral load was also
      negative in the other two patients, and remained so until 18 months of follow-up.
      The medication was well tolerated with no major side effects. Lamivudine was safe
      and effective in blocking HBV replication in renal transplant patients without
      any apparent increase in the risk of graft failure for the 24-month period of
      study.

PMID- 11847524
TI  - Allelic frequencies of six polymorphic markers for risk of prostate cancer.
AB  - The aim of the present study was to evaluate the distribution of polymorphisms
      for the androgen receptor (AR) (CAG, StuI, GGN), SRD5A2 (Ala49Thr, Val89Leu) and
      CYP17 (MspA1) genes that are considered to be relevant for risk of prostate
      cancer. We studied 200 individuals from two cities in the State of Sao Paulo, by
      PCR, PCR-RFLP and ASOH techniques. The allelic frequencies of the autosomal
      markers and the StuI polymorphism of the AR gene were very similar to those
      described in most North American and European populations. In relation to the CAG
      and GGN number of repeats, the study subjects had smaller repeat lengths (mean of
      20.65 and 22.38, respectively) than those described in North American, European
      and Chinese populations. In the present study, 30.5% of the individuals had less
      than 22 CAG repeats and 45.5% had less than 23 GGN repeats. When both repeat
      lengths are considered jointly, this Brazilian population is remarkably different
      from the others. Further studies on prostate cancer patients need to be conducted
      to assess the significance of these markers in the Brazilian population.

PMID- 11847526
TI  - Variability of Vernier acuity measurements in untrained subjects of different
      ages.
AB  - The Vernier acuity of 50 normal untrained subjects (20 males and 30 females) was
      measured by the method of adjustment. Subjects were divided into five age ranges
      with 10 subjects in each age group: 5-10, 11-20, 21-30, 31-40, and 41-50 years.
      All subjects had normal visual acuity (20/20) and volunteered to participate in
      the experiment. Children were selected from a local school and adults recruited
      from the technical staff of the Department of Ophthalmology of the School of
      Medicine. Vernier acuity was higher in adults compared to children.
      Intraindividual variability was high and it was estimated that for most
      individuals of all age groups a range of 100 to 700 trials was necessary to
      obtain a mean with a precision of 10%. These results suggest that Vernier acuity
      variability is an obstacle to its use in clinical settings.

PMID- 11847525
TI  - Biochemical profile of amniotic fluid for the assessment of fetal and renal
      development.
AB  - Creatinine plays a key role in the function and maturation of fetal kidneys
      throughout pregnancy. It is important to identify other markers that may help in
      the diagnosis of renal dysfunction. Our aim was to determine the profile of and
      the correlation between biochemical markers to be used to assess renal function
      and maturation of the fetus in the amniotic fluid during pregnancy and to
      determine the distribution of normal values for creatinine, N-acetyl-beta-D
      glucosaminidase (NAG), beta2-microglobulin, glucose, urea, sodium, potassium,
      phosphorus, calcium, uric acid, albumin, and osmolality in three gestational age
      groups. This was a cross-section study that assessed 115 samples of amniotic
      fluid during three different periods of pregnancy, i.e., 13 to 20, 27 to 34, and
      36 to 42 weeks. Concentrations of creatinine, NAG, urea, potassium and uric acid
      increased during pregnancy (P<0.05). Beta2-microglobulin, glucose, sodium,
      phosphorus, calcium, and albumin concentration and osmolality decreased (P<0.05),
      whereas beta2-microglobulin, glucose and uric acid presented significant
      correlations with gestational age and creatinine, respectively (r>0.6, P<0.05).
      Urea, potassium and phosphorus showed mild correlations with both (r>0.5,
      P<0.05). NAG, sodium, albumin and osmolality did not show significant
      correlations (r<0.5, P<0.05). These tests confirmed the important role of
      creatinine in terms of correlation with gestational age. beta2-Microglobulin,
      glucose and uric acid were significant as markers of function and maturation of
      fetal kidneys, whereas NAG did not demonstrate a useful role for the assessment
      of renal maturation.

PMID- 11847527
TI  - Parathyroid hormone secretion in chronic human endogenous hypercortisolism.
AB  - Osteoporosis is a common manifestation of Cushing's syndrome, but the mechanisms
      responsible for this abnormality have not been defined. With the objective of
      analyzing parathyroid hormone (PTH) secretion in chronic hypercortisolism (CH),
      we evaluated 11 healthy subjects and 8 patients with CH, 6 with Cushing's disease
      and 2 with adrenal adenoma. These volunteers were submitted to tests of PTH
      stimulation through hypocalcemia (EDTA), PTH suppression through hypercalcemia
      (iv and oral calcium), and evaluation of bone mineral density (BMD) by DEXA.
      During the test of PTH stimulation, the calcium and magnesium concentrations of
      the normal and CH groups were similar. Patients with CH showed an increased PTH
      response to the hypocalcemic stimulus compared to controls. PTH values were
      significantly higher in the CH group at 70 (17.5 +/- 3.5 vs 10.2 +/- 1.3 pmol/l,
      P = 0.04), and 120 min (26.1 +/- 5.9 vs 11.3 +/- 1.9 pmol/l, P = 0.008) of EDTA
      infusion. The area under the curve for PTH during EDTA infusion was also
      significantly higher in patients with CH than in normal subjects (1867 +/- 453
      and 805 +/- 148 pmol l(-1) 2 h(-1), P = 0.02). During the test of PTH
      suppression, calcium, magnesium and PTH levels of the patients with
      hypercortisolism and controls were similar. BMD was decreased in patients with
      hypercortisolism in the spine (0.977 +/- 0.052 vs 1.205 +/- 0.038 g/cm2 in
      controls, P<0.01). In conclusion, our results show that subjects with CH present
      decreased bone mass mainly in trabecular bone. The use of dynamic tests permitted
      the detection of increased PTH secretion in response to a hypocalcemic stimulus
      in CH patients that may probably be involved in the occurrence of osteoporosis in
      this state.

PMID- 11847529
TI  - Narrow-band 1, 2, 3, 4, 8, 16 and 24 cycles/360 degrees angular frequency
      filters.
AB  - We measured human frequency response functions for seven angular frequency
      filters whose test frequencies were centered at 1, 2, 3, 4, 8, 16 or 24
      cycles/360 degree using a supra-threshold summation method. The seven functions
      of 17 experimental conditions each were measured nine times for five observers.
      For the arbitrarily selected filter phases, the maximum summation effect occurred
      at test frequency for filters at 1, 2, 3, 4 and 8 cycles/360 degree. For both 16
      and 24 cycles/360 degree test frequencies, maximum summation occurred at the
      lower harmonics. These results allow us to conclude that there are narrow-band
      angular frequency filters operating somehow in the human visual system either
      through summation or inhibition of specific frequency ranges. Furthermore, as a
      general result, it appears that addition of higher angular frequencies to lower
      ones disturbs low angular frequency perception (i.e., 1, 2, 3 and 4 cycles/360
      degree), whereas addition of lower harmonics to higher ones seems to improve
      detection of high angular frequency harmonics (i.e., 8, 16 and 24 cycles/360
      degree). Finally, we discuss the possible involvement of coupled radial and
      angular frequency filters in face perception using an example where narrow-band
      low angular frequency filters could have a major role.

PMID- 11847528
TI  - Acute buspirone abolishes the expression of behavioral dopaminergic
      supersensitivity in mice.
AB  - Previous studies have shown that rats withdrawn from long-term treatment with
      dopamine receptor blockers exhibit dopaminergic supersensitivity, which can be
      behaviorally evaluated by enhanced general activity observed in an open-field.
      Recently, it has been reported that co-treatment with the non-benzodiazepine
      anxiolytic buspirone attenuates the development of haloperidol-induced
      dopaminergic supersensitivity measured by open-field behavior of rats. The aims
      of the present study were: 1) to determine, as previously reported for rats, if
      mice withdrawn from long-term neuroleptic treatment would also develop
      dopaminergic supersensitivity using open-field behavior as an experimental
      paradigm, and 2) to examine if acute buspirone administration would attenuate the
      expression of this behavioral dopaminergic supersensitivity. Withdrawal from long
      term haloperidol treatment (2.5 mg/kg, once daily, for 20 days) induced a
      significant (30%) increase in ambulation frequency (i.e., number of squares
      crossed in 5-min observation sessions) but did not modify rearing frequency or
      immobility duration in 3-month-old EPM-M1 male mice observed in the open-field
      apparatus. Acute intraperitoneal injection of buspirone (3.0 and 10 but not 1.0
      mg/kg, 12-13 animals per group) 30 min before open-field exposure abolished the
      increase in locomotion frequency induced by haloperidol withdrawal. These data
      suggest that the open-field behavior of mice can be used to detect dopaminergic
      supersensitivity, whose expression is abolished by acute buspirone
      administration.

PMID- 11847530
TI  - Resistance of multicellular aggregates to pharmorubicin observed in human
      hepatocarcinoma cells.
AB  - The objective of the present study was to investigate the multicellular
      resistance of human hepatocarcinoma cells BEL-7402 to pharmorubicin. Cells (1 x
      10(4)) and 200 microcarrier Cytodex-3 beads were seeded onto a 24-well plate and
      cultured in RPMI 1640 medium. After the formation of multicellular aggregates,
      morphology and cell viability were analyzed by scanning electron microscopy,
      transmission electron microscopy and flow cytometry, respectively. The IC50 was
      determined by flow cytometry and MTT assay after the cells cultured in aggregates
      and monolayers were treated with pharmorubicin. The culture products exhibited
      structural characteristics somewhat similar to those of trabecular
      hepatocarcinoma in vivo. Among the microcarriers, cells were organized into
      several layers. Intercellular spaces were 0.5-2.0 microm wide and filled with
      many microvilli. The percent of viable cells was 87%. The cells cultured as
      multicellular aggregates were resistant to pharmorubicin with IC50 4.5-fold and
      7.7-fold that of monolayer culture as determined by flow cytometry and MTT assay,
      respectively. This three-dimensional culture model may be used to investigate the
      mechanisms of multicellular drug resistance of hepatocarcinoma and to screen new
      anticancer drugs.

PMID- 11847532
TI  - Dismantling the FDA.

PMID- 11847533
TI  - Tobramycin Serum Concentrations After Aerosol and Oral Administration in Cystic
      Fibrosis.
AB  - We sought to describe tobramycin absorption after aerosol administration to
      cystic fibrosis (CF) subjects. Serum tobramycin concentrations were determined by
      modification of the radioimmuno-assay (RIA) technique, lowering the limit of
      detection from 1.0 &mgr;g ml(minus sign1) to 0.05 &mgr;g ml(minus sign1). In 37
      studies, after aerosol delivery of 666 plus minus 195 mg to the airway of 24
      patients, in which 222 samples were assayed, only 1 serum sample contained
      tobramycin at a concentration greater than 1.0 &mgr;g ml(minus sign1). Twenty-six
      of the 37 studies permitted estimation of pharmacokinetic parameters of
      tobramycin. The serum clearance of tobramycin following aerosol adminstration is
      39.13 plus minus 0.393 L h(minus sign1) (mean plus minus standard error of the
      mean), with an elimination half-life of 3.072 plus minus 0.194 h. The half-life
      was significantly longer than that found after intravenous adminstration. The
      elimination rate constant (K(e)) was calculated to be 0.234 plus minus 0.002
      h(minus sign1). Estimated total-body clearance in which systemic absorption was
      determined from sputum and urinary recovery of tobramycin was 0.094 plus minus
      0.002 1 hr(minus sign1) kg(minus sign1). We also studied tobramycin absorption in
      six CF subjects after ingestion of a 80-mg m(minus sign2) dose, to gain insight
      into the tobramycin levels observed after swallowing an aerosol. Four out of the
      six subjects had measurable serum tobramycin concentration after ingestion. The
      serum concentration-time curve mirrored what was seen after aerosol
      administration. We concluded that tobramycin has poor systemic absorption in CF
      subjects after aerosol administration. Tobramycin in serum after aerosol
      administration is in part due to the gastrointestinal absorption of swallowed
      drug, as well as absorption from lower respiratory tract.

PMID- 11847531
TI  - Albendazole metabolism in patients with neurocysticercosis: antipyrine as a
      multifunctional marker drug of cytochrome P450.
AB  - The present study investigates the isoform(s) of cytochrome P450 (CYP) involved
      in the metabolism of albendazole sulfoxide (ASOX) to albendazole sulfone (ASON)
      in patients with neurocysticercosis using antipyrine as a multifunctional marker
      drug. The study was conducted on 11 patients with neurocysticercosis treated with
      a multiple dose regimen of albendazole for 8 days (5 mg/kg every 8 h). On the 5th
      day of albendazole treatment, 500 mg antipyrine was administered po. Blood and
      urine samples were collected up to 72 h after antipyrine administration. Plasma
      concentrations of (+)-ASOX, (-)-ASOX and ASON were determined by HPLC using a
      chiral phase column and detection by fluorescence. The apparent clearance (CL/f)
      of ASON and of the (+) and (-)-ASOX enantiomers were calculated and compared to
      total antipyrine clearance (CL(T)) and the clearance for the production of the
      three major antipyrine metabolites (CLm). A correlation (P<or=0.05) was obtained
      only between the CL(T) of antipyrine and the CL/f of ASON (r = 0.67). The
      existence of a correlation suggests the involvement of CYP isoforms common to the
      metabolism of antipyrine and of ASOX to ASON. Since the CL(T) of antipyrine is a
      general measure of CYP enzymes but with a slight to moderate weight toward
      CYP1A2, we suggest the involvement of this enzyme in ASOX to ASON metabolism in
      man. The study supports the establishment of a specific marker drug of CYP1A2 in
      the study of the in vivo metabolism of ASOX to ASON.

PMID- 11847534
TI  - Localization of (99m)Tc-Labeled ApoB Synthetic Peptide in Arterial Lesions of an
      Experimental Model of Spontaneous Atherosclerosis.
AB  - We have previously shown that after administration of (123)I-SP-4 (a synthetic
      ApoB peptide fragment) to Watanabe heritable hyperlipidemic (WHHL) rabbits that
      foci of tracer uptake can be identified by external gamma camera imaging which
      correspond to regions of the aortas found to contain abundant atherosclerotic
      lesions at postmortem evaluation. Because (99m)Tc is preferred over (123)I for
      scintigraphic imaging, we prepared a (99m)Tc-labeled form of the SP-4 peptide,
      designated (99m)Tc-P199. To assess the feasibility of detecting atherosclerotic
      lesions using (99m)Tc-P199 and to compare the relative uptake of the (99m)Tc
      labeled and radioiodinated peptides by such lesions, an admixture of (99m)Tc-199
      and (125)I-SP-4 was administered to 11 WHHL and 2 normal rabbits. These animals
      were imaged for up to 3 h and were sacrificed 3--4 h after injection. The extent
      of aortic lesion involvement and radiotracer uptake were quantitatively compared
      by planimetric analysis of photographs of the endothelial surface, (99m)Tc-P199
      ex vivo images and (125)I-SP-4 autoradiograms of the excised aortas. Pairwise
      correlation coefficients for planimetric analysis were as follows: photographs
      versus ex vivo images, r = 0.83, p = 0.003; photographs versus autoradiograms, r
      = 0.87, p = 0.001; ex vivo images versus autoradiograms, r = 0.83, p = 0.003.
      (99m)Tc-199 in vivo gamma camera images revealed relatively weak focal aortic
      uptake in 8 of 11 WHHL rabbits manifesting aortic lesions, and focal carotid
      artery uptake in 4 of 6 WHHL rabbits manifesting carotid lesions. Neither aortic
      nor carotid foci were visualized in the normal rabbits. We conclude that (99m)Tc
      199 localizes specifically in atherosclerotic lesions and may be useful for
      external imaging of atherosclerosis.

PMID- 11847535
TI  - A Nonparametric Alternative to Modeling Population Pharmacokinetics in Patients
      with Spinal Cord Injury: Comparison with the Standard Two-Stage Method.
AB  - The estimation of population-specific pharmacokinetic parameters from sparse of
      fragmentary data obtained during routine patient care is a powerful analytical
      tool in drug development and therapeutic drug monitoring. The Nonparametric
      Expectation Maximization program (NPEM) performs this function and generates
      robust parameter estimates which are distribution-free and unconstrained by
      assumption-rich parametric, for example, Gaussian, analyses. We compared standard
      two-stage method (STS) estimates of amikacin pharmacokinetic parameters (V, CL)
      derived from a sampling rich strategy (11 patients with spinal cord injury, SCI;
      7 able-bodied controls) to estimates of pharmacokinetic parameters obtained from
      an NPEM one-compartment analysis incorporating the 11 optimally sampled SCI
      patients and 8 sparse data sets (19 patients with SCI; 7 controls). The STS (n =
      11) and NPEM (n = 19) analyses provided similar V and CL parameter estimates in
      patients with SCI: 0.20 plus minus 0.04 L kg(minus sign1), 0.93 plus minus 0.24
      ml min(minus sign1) kg(minus sign1) and 0.20 plus minus 0.06 L kg(minus sign1),
      1.12 plus minus 0.26 ml min(minus sign1) kg(minus sign1), respectively. NPEM is a
      useful, user-friendly, distribution-free computational program for estimating the
      central tendency and interindividual variability of amikacin pharmacokinetic
      parameters in spinal cord injured humans.

PMID- 11847536
TI  - Evaluation of Binding Equation Method for Unbound Serum Concentration Prediction
      of Valproic Acid in Polytherapy Pediatric Patients with Epilepsy.
AB  - In a previous study, we determined the in vivo population binding parameters of
      valproic acid (VPA) to serum proteins at single dose in nine healthy young and
      defined a binding equation that was derived from the Scatchard equation. Schever
      et al. and Yu also determined the in vivo population binding parameters of VPA in
      patients with epilepsy receiving VPA monotherapy or polytherapy. In this study,
      we retrospectively evaluated the ability of a binding equation using each of
      population mean binding parameters of Kodama et al. (Method 1), Scheyer et al.
      (Method 2), or Yu (Method 3) to predict the unbound serum VPA concentration in 23
      pediatric patients with epilepsy receiving polytherapy. Mean prediction error,
      mean absolute prediction error (MAE), and root mean squared error (RMSE) were
      separately calculated for each method and served as a measure of prediction bias
      and precision. All three methods were significantly biased, showing a bias to
      overpredict unbound serum VPA. The MAEs and RMSEs for Methods 1 and 2 were
      similar in magnitude (Method 1: MAE = 16.5, RMSE = 23.1; Method 2: MAE = 14.0,
      RMSE = 17.5). On the other hand, each value for Method 3 was extremely high (MAE
      = 32.8 and RMSE = 36.3). Method 3 is apparently inferior to other two methods in
      accuracy and precision. For Methods 1 and 2, similar tendency to overprediction
      was observed in total concentration above 400 &mgr;mol L(minus sign1). These two
      methods may be useful to patients with total VPA lower than 400 &mgr;mol L(minus
      sign1).

PMID- 11847537
TI  - Pharmacokinetics in Non-Insulin-Dependent Diabetics of the Aldose Reductase
      Inhibitor, Zopolrestat.
AB  - The pharmacokinetics of zopolrestat have been examined in non-insulin-dependent
      diabetic patients after oral administration of a single dose of 1000 mg
      zopolrestat. T(max) ranged from 2 to 4 h with a mean C(max) of 100 &mgr;g
      ml(minus sign1). Mean plasma half-life of zopolrestat was 26.9 h. The same
      patients were also administered oral doses of 1000 mg day(minus sign1) for 10
      consecutive days. Mean T(max) was 4.3 h and mean C(max) was 208 &mgr;g ml(minus
      sign1). Plasma accumulation, the ratio of AUC((0--24)) for the last dose to
      AUC((0--24)) for the first dose, was 2.67. Apparent oral clearance was 5.71 ml
      min(minus sign1) and apparent volume of distribution was 12.9 L. The mean urinary
      excretion of unchanged drug over the 24-h period following the last dose was 36%
      of the dose while another 7% of the dose appeared in the urine as an
      acylglucuronide of zopolrestat. Renal clearance of zopolrestat was 1.82 ml
      min(minus sign1). Binding of zopolrestat to plasma proteins exceeded 99% and was
      concentration dependent.

PMID- 11847538
TI  - Coronary Thrombolysis.
AB  - Randomized trials have demonstrated the overall benefits and risks of
      thrombolytic therapy for acute myocardial infarction, and have evaluated
      adjunctive drug therapies, adjunctive and primary angioplasty, various approaches
      to the timing of thrombolysis, and post-thrombolysis management. Three questions,
      which remain unanswered, are addressed in this Point-Counterpoint Series. The
      GUSTO trial provides convincing evidence of the greater efficacy of rt-PA by
      comparison to SK, but the size of the benefit is uncertain, as are the risk
      benefit ratios and cost-effectiveness in various patient subgroups. The issues of
      whether or not routine angiography is appropriate for patients who have received
      coronary thrombolysis remains unresolved. For the present, clinical guidelines
      are likely to advise against routine angiography, while many cardiologists,
      concerned about the shortcomings of available studies, may wish to undertake
      coronary angiography in many of their patients, even though definitive proof of
      its benefit is lacking. Although randomized clinical trials suggest a benefit of
      primary angioplasty over thrombolytic therapy, further studies are required to
      clarify the comparative benefits in terms of clinically important outcomes and
      cost-effectiveness.

PMID- 11847539
TI  - New Accelerated rt-PA Strategy Has Sufficient Advantage over Older Streptokinase
      Strategies that It should Be the Trhombolytic Strategy of Choice in Anterior and
      Large Infarctions.
AB  - The major goal of myocardial reperfusion therapy is to restore normal coronary
      blood flow as quickly as possible and to maintain coronary patency in the highest
      number of patients with acute myocardial infarction. Recent studies support the
      hypothesis that more rapid and complete restoration of coronary flow through the
      infarct-related artery results in improved ventricular performance and lower
      mortality. Accelerated tissue plasminogen activator therapy appears to produce
      the most favorable effects compared to other lytic strategies, particularly in
      patients with anterior and large myocardial infarctions. However, the finding in
      GUSTO II trial, that even with the best strategy only 54% of patients had TIMI
      grade 3 flow, suggests that further improvement in the treatment of acute
      myocardial infarction may be possible in the future. The effectiveness of
      thrombolytic therapy may be enhanced by earlier identification of evolving
      myocardial infarction and reduced time delays in the initiation of thrombolytic
      therapy, bolus thrombolytic therapy, new thrombolytic agents, or more potent
      adjunctive antithrombotic strategies.

PMID- 11847540
TI  - Streptokinase Is Still the Agent of Choice for Most Patients with Myocardial
      Infarction.
AB  - I believe streptokinase is still the trombolytic of choice for the majority of
      patients with acute myocardial infarction for the following reasons: 1. The
      superiority of alteplase over streptokinase rests on insecure grounds,
      statistically (when net clinical benefit is computed for the SK/subcutaneous
      heparin arm versus the accelerated t-PA arm, the P value is only 0.04). 2. The
      excess of cerebral haemorrhage with t-PA is statistically highly significant and
      consistent over all trials. 3. Patients at greater risk of cerebral hemorrhage
      are those with raised systolic arterial pressure above about 130 to 140 on
      admission and those aged over about 55 years. These comprise the majority of
      patients admitted to ordinary Coronary Care Units. If t-PA is given to patients
      at low risk of cerebral hemorrhage, the extra cost per life saved will be very
      high, since such patients are at relatively low risk in any case. 4. The open
      design of the GUSTO-2 trial (the only trial showing a small mortality benefit for
      accelerated t-PA versus SK) introduces the possibility of bias. For example,
      unfamiliarity with SK in North American centers may have given risk to premature
      stopping of treatment because of hypotension; this might have resulted in a more
      favorable experience for accelerated t-PA in North American centers compared with
      the rest of the world. (The mortality benefit for accelerated t-PA in the GUSTO
      trial was seen only in North American centers.)

PMID- 11847541
TI  - Routine, Early, Coronary Angiography Following Thrombolysis for Acute Myocardial
      Infarction.
AB  - Over the last decade the use of thrombolytic therapy for patients with acute
      myocardial infarction has resulted in a substantial mortality reduction. While
      the utility of thrombolytic therapy is now widely recognized, the role of post
      infarction coronary angiography remains controversial. In this report we examine
      the early studies which investigated the necessity and timing of angiography
      following thrombolysis, and review recent data that underscore the importance of
      achieving early infarct-related arterial patency. In place of a strategy of
      "selective angiography," we present an argument for routine, early coronary
      angiography following thrombolytic therapy for acute myocardial infarction.

PMID- 11847542
TI  - Coronary Arteriography Should Not Be Routinely Used Postinfarction in Patients
      Having Received Thrombolytic Therapy.
AB  - The use of thrombolytic agents in the context of an acute myocardial infarction
      has resulted in a significant decrease in postinfarction mortality. However, at
      this time, little information supporting the routine use of invasive diagnostic
      and therapeutic interventions in all patients with acute myocardial infarction
      having received thrombolytic agents is available. Rather, the available data
      support a conservative strategy, which recommends the judicious use of these
      techniques in patients with evidence of clinical ongoing ischemia or in patients
      with a positive predischarge exercise stress test. Several potential explanations
      have been identified, the most important being the instability of the plaque in
      the early postinfarction period and the importance of functional capacity as an
      independent risk factor for subsequent morbidity and mortality. Until studies
      showing that routine coronary arteriography improves the prognosis of patients
      with negative predischarge exercise tests, we believe that it will be difficult
      to justify routine coronary arteriography even in patients with left ventricular
      dysfunction postinfarction. This more conservative approach should result in
      significant savings and a more rational use of available resources.

PMID- 11847543
TI  - Primary Angioplasty Is the Optimal Approach to Early Reperfusion in Patients with
      Acute Myocardial Infarction.
AB  - Primary angioplasty offers several advantages to thrombolysis for the treatment
      of acute myocardial infarction. First, most patients are candidates for primary
      angioplasty. In contrast, only 20--30% meet eligibility criteria for
      thrombolysis. Second, angioplasty is superior to thrombolysis in achieving
      infarct artery patency, restoring normal coronary blood flow, and preventing
      temporary or permanent reocclusion. Third, angioplasty results in lower rates of
      mortality, recurrent ischemia, or stroke than thrombolysis. Finally, the cost of
      an angioplasty strategy is lower than the thrombolysis strategy due to earlier
      hospital discharge, fewer expensive complications, and fewer subsequent
      procedures and hospitalizations.

PMID- 11847545
TI  - The Governmental Revolution.

PMID- 11847544
TI  - The Relative Merits of Direct Angioplasty versus Intravenous Thrombolytic Therapy
      for the Treatment of Acute Myocardial Infarction.
AB  - There is growing interest in the use of angioplasty as the primary method to
      achieve coronary artery reperfusion in patients with acute myocardial infarction.
      The use of thrombolytic therapy has been established as effective in many large
      clinical trials, while only a few small studies have been completed comparing
      primary angioplasty with thrombolytic therapy. This paper briefly compares the
      use of these two treatment modalities and concludes that primary angioplasty is
      the preferred approach in patients with cardiogenic shock and for those patients
      with large myocardial infarctions who have contraindications to thrombolytic
      therapy. Other patients with AMI should receive thrombolytic therapy unless there
      are contraindications to this treatment.

PMID- 11847546
TI  - ACE Inhibitors as First-Line Treatment Agents: A Comparative Study of
      Trandolapril and Enalapril on Casual and Ambulatory Blood Pressures.
AB  - This double-blind, randomized, parallel-ground study was designed to compare the
      efficacy of the angiotensin-converting enzyme inhibitors, trandolapril and
      enalapril, in 65 patients with mild to moderate primary hypertension. After a 4
      week, single-blind, placebo run-in period, patients were randomized to receive
      either trandolapril 0.5 mg or enalapril 2.5 mg once daily. At 2-week intervals,
      trandolapril was titrated to 1, 2, or 4 mg and enalapril to 5, 10, or 20 mg in
      order to achieve a goal supine diastolic blood pressure (BP) of <90 mm Hg. In
      addition to casual BP measurement, 24-h ambulatory BP monitoring was performed at
      the end of the placebo period (baseline) and after 10 weeks of stable therapy at
      optimal and/or maximal dosage. Both drugs induced significant and comparable
      decreases in clinic systolic and diastolic BPs. The mean doses used were 3.2 mg
      for trandolapril and 16.6 mg of enalapril. The maximal effect was obtained at the
      highest dosage for both drugs in most patients with a mean decrease in supine
      diastolic BP of 8.6 mm Hg and 7.3 mm Hg for trandolapril 4 mg and enalapril 20
      mg, respectively. Moreover, both agents significantly and similarly reduced mean
      24-h as well as awake and sleep ambulatory BPs. Heart rates remained unchanged
      throughout the study. Our results demonstrate that both trandolapril and
      enalapril given at high dose exhibited significant decreases in clinic as well as
      in 24-h, awake, and sleep ambulatory BPs with no clear-up difference between the
      two treatment regimens. Moreover, our results emphasize the role of ambulatory BP
      monitoring when assessing the efficacy as well as the duration of action of new
      antihypertensive agents.

PMID- 11847547
TI  - Beneficial Effect of a Long-Term Antihypertensive Therapy on Blood Pressure
      Response to Isometric Handgrip Exercise in Patients with Essential Hypertension.
AB  - To elucidate the effect of a long-term antihypertensive therapy on blood pressure
      (BP) response to isometric handgrip exercise (IHG) in patients with essential
      hypertension (EHT, n = 16), IHG was carried out at 30% maximal voluntary
      contraction of right hand for 3 min before therapy and after a long-term
      antihypertensive therapy. BP responsiveness to IHG was estimated by the
      difference between values obtained at rest and at 3 min during IHG (change of
      systolic BP = DeltaSBP, change of diastolic BP = DeltaDBP. Both DeltaSBP and
      DeltaDBP before therapy were markedly greater in EHT (DeltaSBP = 64 plus minus 18
      mm Hg, DeltaDBP = 33 plus minus 9 mm Hg) than in age-mathced normotensive
      controls (NT, n = 8, 29 plus minus 4 mm Hg, 18 plus minus 4 mm Hg). By
      antihypertensive therapy, SBP and DBP in EHT were decreased from 152 plus minus
      22 mm Hg to 136 plus minus 14 mm Hg and from 90 plus minus 18 mm Hg to 83 plus
      minus 10 mm Hg, respectively, but both SBP and DBP in EHT after antihypertensive
      therapy were still greater than those in NT. Both DeltaSBP and DeltaDBP in EHT
      after a long-term antihypertensive therapy were significantly smaller than those
      in EHT before therapy but were still significantly larger than those in NT. These
      results demonstrate that a long-term antihypertensive therapy reduces the
      exaggerated BP response to IHG in EHT.

PMID- 11847548
TI  - Postprandial Hemodynamic Changes in Hypertensives Treated with Calcium
      Antagonists or ACE Inhibitors.
AB  - Our aim was to investigate possible abnormalities in postprandial hemodynamic
      changes in hypertensives treated with different vasodilating drugs, calcium
      antagonists, or angiotensin-converting enzyme inhibitors. Eleven healthy subjects
      and 22 hypertensive patients effectively treated with an angio tensin-converting
      enzyme inhibitor (ACEI) (n = 9) or calcium antagonists (n = 13) were studied.
      Cardiac output and blood pressure were monitored every 20 min from 2 h before
      lunch to 3 h after using a computer-assisted impedance cardiograph coupled with
      an automatic blood pressure monitor. After meals, a significant decrease in mean
      arterial pressure (minus sign7.9% plus minus 2.1) was observed in ACEI-treated
      hypertensives when compared with the minor changes observed in calcium-antagonist
      treated hypertensives (minus sign3.7% plus minus 1.5) and in normotensives (minus
      sign2.7% plus minus 1.5). When compared with normotensives, the patients treated
      with ACEI showed a larger postprandial fall in total peripheral resistance index
      (minus sign20.8% plus minus 3.4 versus minus sign15.3% plus minus 4.1) with a
      larger increase in heart rate (11.3% plus minus 2.3 versus 8.1% plus minus 1.3).
      In hypertensives treated with calcium antagonists, the postprandial hemodynamic
      changes appeared blunted and not significant. Different antihypertensive drugs
      appear to have different effects on the postprandial hemodynamic changes.

PMID- 11847549
TI  - Dopaminergic Influence on the Cardiovascular and Hormonal Responses to Cold
      Stress in Hypertensive Patients.
AB  - Immersion of one hand into ice water (cold pressor test) in eight hypertensive
      subjects induces elevation of mean arterial pressure, increase in heart rate, and
      no significant changes of plasma renin activity and plasma aldosterone
      concentrations. Domperidone, a DA2 dopaminergic antagonist, attenuates heart rate
      increase induced by the cold pressor test, and the combination of bromocriptine,
      a known DA2 dopaminergic agonist, with domperidone again provoked a heart rate
      increase during the cold pressor test. Domperidone caused an increase of both
      plasma renin activity and plasma aldosterone concentrations, which were reversed
      by bromocriptine. These results suggest that a dopamine-receptor stimulation is
      taking place during the cold pressor test.

PMID- 11847550
TI  - Dose--Response Study of Colestipol Tablets in Patients with Moderate
      Hypercholesterolemia.
AB  - The purpose of the study was to evaluate the efficacy and safety of a new
      formulation of colestipol provided in table form. This was a randomized, double
      blind, placebo-controlled, multicenter, dose-ranging study. A total of 196
      patients with primary hypercholesterolemia who were following a low-fat, low
      cholesterol diet (NCEP Step I diet), and having mean low-density lipoprotein
      cholesterol (LDL-C) levels greater-than-or-equal4.14 mmol L(minus sign1) (160 mg
      dl(minus sign1)) and less-than-or-equal6.46 mmol L(minus sign1) (250 mg dl(minus
      sign1)) were studied. Study medication was taken twice daily, with breakfast and
      supper, for 8 weeks. The five parallel treatment groups consisted of colestipol
      tablets 1, 2, 4, and 8 g BID, and matching placebo tablets BID. The main outcome
      measures were absolute change and percent change from baseline in selected lipid,
      lipoprotein, and apolipoprotein measurements; LDL-C was considered primary.
      Statistically significant (p less-than-or-equal 0.05) dose-dependent reductions
      in LDL-C from 5.2% to 25.8% and in total cholesterol from 2.8% to 16.8% were
      observed. Colestipol tablet treatment also resulted in statistically significant
      dose-dependent increases in LpAl levels reaching 25.8% at 16 g day(minus sign1).
      The treatment was well tolerated, and no serious adverse events were reported.
      Colestipol administered in tablet form was efficacious in lowering LDL-C and
      total cholesterol and was well tolerated in patients with primary
      hypercholesterolemia.

PMID- 11847551
TI  - Bioequivalence of Two Recombinant Human Growth Hormones in Healthy Male
      Volunteers after Subcutaneous Administration.
AB  - The bioequivalence of recombinant human growth hormone (rhGH) (somatropin) and
      its N-methionyl variant (Met-hGH) [Protropin((R)) (somatrem for injection)] was
      determined in 42 healthy male volunteers (n = 21 per treatment) who were
      randomized to receive either protein by subcutaneous administration of 0.1 mg
      kg(minus sign1). Serum samples were collected over 24 h after the injection, and
      the concentration of human growth hormone (hGH) were determined by an
      immunoradiometric assay. Bioequivalence of the two proteins was assessed by
      determining whether the 90% confidence limits for the ratio of geometric means
      using logarithmically transformed AUC and C(max) parameters (log(10)AUC(0--24),
      log(10)AUC(0--infty infinity), and log(10)C(max)) were within the 80--125% range.
      The bioequivalence of the two treatments was also tested by calculating a
      bioequivalance index (xi(2)) that measured the difference between the two mean
      concentration-time profiles. The 90% confidence intervals for the ratios of the
      geometric means for AUC were within the prescribed 80--125% range for
      bioequivalence. The upper limit of the 90% confidence interval for the ratio of
      the geometric means for C(max) fell slightly outside the 125% criterion even
      though the geometric mean itself, 106.6%, was very close to the ideal of 100%.
      There was a larger standard error associated with C(max) than with the AUCs, and
      this marginally larger confidence limit for C(max) resulted more from the
      variance among the subject than to the difference in the means. In fact, the
      bioequivalence index, xi(2), was 0.075, indicating that the mean curves after
      rhGH and Met-hGH are essentially superimposable.

PMID- 11847553
TI  - The Placebo Effect: A Brief Review.
AB  - The placebo effect is a most curious phenomenon, which has been known since
      ancient times. After World War II, it became an important methodological tool in
      the conduction of clinical trials. The so-called "placebo-reactors" show special
      sensitivity to these inert substances. In general, 35.5 plus minus 2.2% of
      patients affected by various conditions proved to react positively to placebos.
      Several aspects of placebos seem to play a relevant potentiating action on such
      effects. In this context, surgical rather than clinical seems to be a more
      efficient placebo. Despite a clearcut role of the limbic system, emphasis has
      been placed on psychological aspects of the possible pathophysiologic mechanisms.

PMID- 11847552
TI  - Pentostatin (2prime prime or minute-Deoxycoformycin): Clinical Pharmacology, Role
      In Cancer Chemotherapy, and Future Prospects.
AB  - Pentostatin (2prime prime or minute-deoxycoformycin, dCF) is a product of the
      fermentation of Streptomyces antibioticus. It is a tight-binding inhibitor of
      adenosine deaminase (ADA), an enzyme essential in cellular metabolism of purines.
      Children with congenital absence of ADA suffer from atrophy of lymphoid tissues
      and severe combined immune deficiency (SCID) syndrome. It was speculated that
      pentostatin would be lymphocytotoxic, and this proved to be the case, promoting
      its investigation in lymphoid neoplasms. It was anticipated that pentostatin
      would be most active in neoplasms with high intracellular concentrations of ADA--
      e.g., acute lymphocytic leukemia (ALL), particularly its T cell variety. Although
      pentostatin proved to be active in ALL, large doses were required and toxic
      effects outweighted therapeutic benefits. By contrast, pentostatin proved to be
      exceptionally active in hairy cell leukemia (HCL), a B cell neoplasm with low
      intracellular concentrations of ADA. Pentostatin has since been shown to possess
      activity in chronic lymphocytic leukemia, prolymphocytic leukemia, cutaneous T
      cell lymphomas, adult T cell lymphoma-leukemia, and low-grade non-Hodgkin's
      lymphomas. It potentiates the activity of vidarabine against viruses and against
      the cells of acute myeloid leukemia. Pentostatin is inactive in melanoma and
      renal carcinoma, but has not been adequately evaluated in other solid tumors. The
      toxic effects of pentostatin include renal failure, central nervous system (CNS)
      depression, immunosuppression, keratoconjunctivitis, and opportunistic
      infections. In the absence of pre-existing bone marrow compromise, pentostatin
      produces only mild myelosuppression. Aside from its use as an antineoplastic
      agent, pentostatin has potential applications as an immunosuppresive drug, as an
      antiviral agent, as an antimalarial compound, and in the protection of cells of
      the CNS from damage induced by ischemia and anoxia.

PMID- 11847554
TI  - Bacterial Arthritis: A Diagnostic and Therapeutic Approach.

PMID- 11847555
TI  - Evolution of human Polyomavirus JC: implications for the population history of
      humans.
AB  - The polyomavirus JC virus (JCV), the etiological agent of progressive multifocal
      leukoencephalopathy, is ubiquitous in the human population, infecting children
      asymptomatically, then persisting in the kidney. The main mode of transmission of
      JCV is from parents to children through long-term cohabitation. Twelve JCV
      subtypes that occupy unique domains in Europe, Africa, and Asia have been
      identified. Here, we attempted to elucidate the evolutionary relationships among
      JCV strains worldwide using the whole-genome approach with which a highly
      reliable phylogeny of JCV strains can be reconstructed. Sixty-five complete JCV
      DNA sequences, derived from various geographical regions and belonging to 11 of
      the 12 known subtypes, were subjected to phylogenetic analysis using three
      independent methods: the neighbor-joining, maximum parsimony, and maximum
      likelihood methods. The trees obtained with these methods consistently indicated
      that ancestral JCVs were divided into three superclusters, designated as Types A,
      B, and C. A split in Type A generated two subtypes, EU-a and -b, mainly
      containing European and Mediterranean strains. The first split in Type B
      generated Af2 (the major African subtype). Subsequent splits in Type B generated
      B1-c (a minor European subtype) and all seven Asian subtypes (B1-a, -b, -d, B2,
      MY, CY, and SC). Type C generated a single subtype (Af1), consisting of strains
      derived from western Africa. While the present findings provided a basis on which
      to classify JCV into types or subtypes, they have several implications for the
      divergence and migration of human populations.

PMID- 11847556
TI  - Phenylalanine-binding RNAs and genetic code evolution.
AB  - We isolated RNAs by selection-amplification, selecting for affinity to Phe
      Sepharose and elution with free l-phenylalanine. Constant sequences did not
      contain Phe condons or anticodons, to avoid any possible confounding influence on
      initially randomized sequences. We examined the eight most frequent Phe-binding
      RNAs for inclusion of coding triplets. Binding sites were defined by nucleotide
      conservation, protection, and interference data. Together these RNAs comprise 70%
      of the 105 sequenced RNAs. The KD for the strongest sites is approximately 50
      microM free amino acid, with strong stereoselectivity. One site strongly
      distinguishes free Phe from Trp and Tyr, a specificity not observed previously.
      In these eight Phe-binding RNAs, Phe codons are not significantly associated with
      Phe binding sites. However, among 21 characterized RNAs binding Phe, Tyr, Arg,
      and Ile, containing 1342 total nucleotides, codons are 2.7-fold more frequent
      within binding sites than in surrounding sequences in the same molecules. If
      triplets were not specifically related to binding sites, the probability of this
      distribution would be 4.8 x 10(-11). Therefore, triplet concentration within
      amino acid binding sites taken together is highly likely. In binding sites for
      Arg, Tyr, and Ile cognate codons are overrepresented. Thus Arg, Tyr, and Ile may
      be amino acids whose codons were assigned during an era of direct RNA-amino acid
      affinity. In contrast, Phe codons arguably were assigned by another criterion,
      perhaps during later code evolution.

PMID- 11847557
TI  - Cloning and molecular characterization of the first innexin of the phylum
      annelida-expression of the gene during development.
AB  - A novel member of the innexin family (cv-inx) has been isolated from the annelid
      polychaete worm Chaetopterus variopedatus using a PCR approach on genomic DNA and
      sequence analysis on genomic DNA clones. The gene is present in a HindIII-HindIII
      segment of 2250 bp containing an uninterrupted open reading frame of 1196 bp
      encoding a protein of 399 amino acids. The predicted protein shows the typical
      structural features of innexins and consensus sites for phosphorylation. Analyses
      on genomic DNA demonstrate that cv-inx is a single copy gene with no introns in
      the coding region, exactly corresponding to the cDNA sequence. The gene
      expression is regulated during development as shown by Northern blots analyses of
      the RNA and by immunoreaction with antibodies against the protein at several
      embryonic stages. The finding of an innexin in the phylum Annelida, outside of
      the Ecdysozoa clade, and its peculiar gene structure suggest the necessity to
      reconsider the current hypothesis on the origin and evolution of gap junctional
      proteins.

PMID- 11847558
TI  - Sucrose phosphate synthase genes in plants belong to three different families.
AB  - We present phylogenetic analyses to demonstrate that there are three families of
      sucrose phosphate synthase (SPS) genes present in higher plants. Two data sets
      were examined, one consisting of full-length proteins and a second larger set
      that covered a highly conserved region including the 14-3-3 binding region and
      the UDPGlu active site. Analysis of both datasets showed a well supported
      separation of known genes into three families, designated A, B, and C. The
      genomic sequences of Arabidopsis thaliana include a member in each family: two
      genes on chromosome 5 belong to Family A, one gene on chromosome 1 to Family B,
      and one gene on chromosome 4 to Family C. Each of three Citrus genes belong to
      one of the three families. Intron/exon organization of the four Arabidopsis genes
      differed according to phylogenetic analysis, with members of the same family from
      different species having similar genomic organization of their SPS genes. The two
      Family A genes on Arabidopsis chromosome 5 appear to be due to a recent
      duplication. Analysis of published literature and ESTs indicated that functional
      differentiation of the families was not obvious, although B family members appear
      not to be expressed in roots. B family genes were cloned from two Actinidia
      species and southern analysis indicated the presence of a single gene family,
      which contrasts to the multiple members of Family A in Actinidia. Only two family
      C genes have been reported to date.

PMID- 11847559
TI  - Evolved RNA secondary structure and the rooting of the universal tree of life.
AB  - The origin and diversification of RNA secondary structure were traced using
      cladistic methods. Structural components were coded as polarized and ordered
      multi-state characters, following a model of character state transformation
      outlined by considerations in statistical mechanics. Several classes of
      functional RNA were analyzed, including ribosomal RNA (rRNA). Considerable
      phylogenetic signal was present in their secondary structure. The intrinsically
      rooted phylogenies reconstructed from evolved RNA structure depicted those
      derived from nucleic acid sequence at all taxonomical levels, and grouped
      organisms in concordance with traditional classification, especially in the
      archaeal and eukaryal domains. Natural selection appears therefore to operate
      early in the information flow that originates in sequence and ends in an adapted
      phenotype. When examining the hierarchical classification of the living world,
      phylogenetic analysis of secondary structure of the small and large rRNA subunits
      reconstructed a universal tree of life that branched in three monophyletic groups
      corresponding to Eucarya, Archaea, and Bacteria, and was rooted in the eukaryotic
      branch. Ribosomal characters involved in the translational cycle could be easily
      traced and showed that transfer RNA (tRNA) binding domains in the large rRNA
      subunit evolved concurrently with the rest of the rRNA molecule. Results suggest
      it is equally parsimonious to consider that ancestral unicellular eukaryotes or
      prokaryotes gave rise to all extant life forms and provide a rare insight into
      the early evolution of nucleic acid and protein biosynthesis.

PMID- 11847560
TI  - Uneven distribution of repetitive trinucleotide motifs in human immunoglobulin
      heavy variable genes.
AB  - Insertions and deletions of entire codons have recently been discovered as a
      mechanism by which B cells, in addition to conventional base substitution, evolve
      the antibodies produced by their immunoglobulin genes. These events frequently
      seem to involve repetitive sequence motifs in the antibody-encoding genes, and it
      has been suggested that they occur through polymerase slippage. In order to
      better understand the process of codon deletion, we have analyzed the human
      immunoglobulin heavy variable (IGHV) germline gene repertoire for the presence of
      trinucleotide repeats. Such repeats would ensure that the reading frame is
      maintained in the case of a deletional event, as slippage over multiples of three
      bases would be favored. We demonstrate here that IGHV genes specifically carry
      repetitive trinucleotide motifs in the complementarity-determining regions (CDR)
      1 and 2, thus making these parts of the genes that encode highly flexible
      structures particularly prone to functional deletions. We propose that the human
      IGHV repertoire carries inherent motifs that allow an antibody response to
      develop efficiently by targeting codon deletion events to the parts of the
      molecule that are likely to be able to harbor such modifications.

PMID- 11847561
TI  - Evolutionary history of 4.5SI RNA and indication that it is functional.
AB  - To date, the small nuclear 4.5SI RNA has only been studied in the rat (Rattus
      norvegicus). Combining PCR and hybridization analyses, we have revealed 4.5SI RNA
      homologues sequences in the genomes of four myomorph rodent families (Muridae,
      Cricetidae, Spalicidae, and Rhizomyidae), and not in other myomorph families
      (Dipodidae, Zapodidae, Geomyidae, and Heteromyidae) or sciuromorph and caviomorph
      rodents. By Northern-hybridization, 4.5SI RNA has been detected in the common rat
      (R. norvegicus, Muridae), golden hamster (Mesocricetus auratus, Cricetidae), and
      Russian mole rat (Spalax microphthalmus, Spalacidae), but not in the related
      great jerboa (Allactaga jaculus, Dipodidae) or in four non-myomorph rodent
      species tested. cDNA derived from 4.5SI RNA of M. auratus and S. microphthalmus
      has been cloned and sequenced. The hamster RNA is found to differ from rat 4.5SI
      RNA by only one nucleotide substitution. For the mole rat, two variants of 4.5SI
      RNA are detected: short (S) and long (L) with length 101 and 108 nt,
      respectively. The L variant differs from the S variant as well as from murid and
      cricetid 4.5SI RNAs by both a 7 nt insertion and a varying number of nucleotide
      substitutions. The sequence similarity between the spalacid S-variant and
      murid/crecitid variants of 4.5SI RNA is 90%. Judging from species distribution,
      4.5SI RNA genes emerged during the same period of time as the related short
      interspersed element B2 arose. This occurred after the divergence of Dipodidae
      lineage but before the branching of Spalicidae/Rhizomyidae lineage from a common
      myomorph rodent stem. S variant genes seemed to emerge in a common ancestor of
      spalacids and rhizomyds whereas L variant genes formed in spalacids following the
      divergence of these two families. The low rate of evolutionary changes of 4.5SI
      RNA, at least, in murids and cricetids (6 x 10(-4) substitutions per site per
      million years), suggests that this RNA is under selection constraint and have a
      function. This is a remarkable fact if the recent origin and narrow species
      distribution range of 4.5SI RNA genes is taken into account. Genes with narrow
      species distribution are proposed to be referred to as stenogenes.

PMID- 11847562
TI  - Detection of genes with atypical nucleotide sequence in microbial genomes.
AB  - Along the gene, nucleotides in various codon positions tend to exert a slight but
      observable influence on the nucleotide choice at neighboring positions. Such
      context biases are different in different organisms and can be used as genomic
      signatures. In this paper, we will focus specifically on the dinucleotide
      composed of a third codon position nucleotide and its succeeding first position
      nucleotide. Using the 16 possible dinucleotide combinations, we calculate how
      well individual genes conform to the observed mean dinucleotide frequencies of an
      entire genome, forming a distance measure for each gene. It is found that genes
      from different genomes can be separated with a high degree of accuracy, according
      to these distance values. In particular, we address the problem of recent
      horizontal gene transfer, and how imported genes may be evaluated by their poor
      assimilation to the host's context biases. By concentrating on the third- and
      succeeding first position nucleotides, we eliminate most spurious contributions
      from codon usage and amino-acid requirements, focusing mainly on mutational
      effects. Since imported genes are expected to converge only gradually to genomic
      signatures, it is possible to question whether a gene present in only one of two
      closely related organisms has been imported into one organism or deleted in the
      other. Striking correlations between the proposed distance measure and poor
      homology are observed when Escherichia coli genes are compared to Salmonella
      typhi, indicating that sets of outlier genes in E. coli may contain a high number
      of genes that have been imported into E. coli, and not deleted in S. typhi.

PMID- 11847563
TI  - Phylogeny derived from coding retroviral genome organization.
AB  - When divergence between viral species is large, the analysis and comparison of
      nucleotide or protein sequences are dependent on mutation biases and multiple
      substitutions per site leading, among other things, to the underestimation of
      branch lengths in phylogenetic trees. To avoid the problem of multiply
      substituted sites, a method not directly based on the nucleic or protein
      sequences has been applied to retroviruses. It consisted of asking questions
      about genome structure or organization, and gene function, the series of answers
      creating coded sequences analyzed by phylogenic software. This method recovered
      the principal retroviral groups such as the lentiviruses and spumaviruses and
      highlighted questions and answers characteristic of each group of retroviruses.
      In general, there was reasonable concordance between the coded genome methodology
      and that based on conventional phylogeny of the integrase protein sequence,
      indicating that integrase was fixing mutations slowly enough to marginalize the
      problem of multiple substitutions at sites. To a first approximation, this
      suggests that the acquisition of novel genetic features generally parallels the
      fixation of amino acid substitutions.

PMID- 11847564
TI  - The antigen receptor (NCCRP-1) on catfish and zebrafish nonspecific cytotoxic
      cells belongs to a new gene family characterized by an F-box-associated domain.
AB  - The catfish nonspecific cytotoxic cell receptor protein (NCCRP-1) provides an
      important function in target cell recognition and activation of cytotoxicity.
      This report identifies and characterizes a zebrafish orthologue of the catfish
      NCCRP-1. The zebrafish NCCRP-1 cDNA contains an open reading frame that encodes a
      predicted protein of 237 amino acids with a MW of 27 kDa and a pI of 5.5.
      Sequence similarities comparisons show that the NCCRP-1 receptors from these two
      phylogenetically distant species share a high degree of identity. These results
      suggested that NCCRP-1 performs a crucial function in innate immunity in
      teleosts. Further, a zebrafish 17-mer peptide corresponding to the catfish NCCRP
      1 antigen-binding domain inhibited (catfish) cytotoxicity toward conventional
      tumor target cells (HL-60). These data appeared to indicate that the zebrafish
      NCCRP-1 protein may function as an antigen recognition molecule and, as such, may
      participate in innate immunity in teleosts. A homology search of the zebrafish
      NCCRP-1 protein revealed that it shares a significant level of identity with
      another group of proteins belonging to an F-box subfamily. These proteins share
      an F-box domain in the N terminus (not present in NCCRP-1) and an extremely
      conserved C-terminal region that has been termed the F-box-associated domain
      (FBA). The FBA is currently of unknown function. A new gene family is proposed in
      this work, based on similarities in the FBA sequences with the catfish and
      zebrafish NCCRP-1 peptides. This new gene family includes several F-box domain
      containing proteins and a predicted C. elegans protein.

PMID- 11847565
TI  - The effect of recombination on the accuracy of phylogeny estimation.
AB  - Phylogenetic studies based on DNA sequences typically ignore the potential
      occurrence of recombination, which may produce different alignment regions with
      different evolutionary histories. Traditional phylogenetic methods assume that a
      single history underlies the data. If recombination is present, can we expect the
      inferred phylogeny to represent any of the underlying evolutionary histories? We
      examined this question by applying traditional phylogenetic reconstruction
      methods to simulated recombinant sequence alignments. The effect of recombination
      on phylogeny estimation depended on the relatedness of the sequences involved in
      the recombinational event and on the extent of the different regions with
      different phylogenetic histories. Given the topologies examined here, when the
      recombinational event was ancient, or when recombination occurred between closely
      related taxa, one of the two phylogenies underlying the data was generally
      inferred. In this scenario, the evolutionary history corresponding to the
      majority of the positions in the alignment was generally recovered. Very
      different results were obtained when recombination occurred recently among
      divergent taxa. In this case, when the recombinational breakpoint divided the
      alignment in two regions of similar length, a phylogeny that was different from
      any of the true phylogenies underlying the data was inferred.

PMID- 11847566
TI  - Positive darwinian selection promotes heterogeneity among members of the
      antifreeze protein multigene family.
AB  - A variety of organisms have independently evolved proteins exhibiting antifreeze
      activity that allows survival at subfreezing temperatures. The antifreeze
      proteins (AFPs) bind ice nuclei and depress the freezing point by a
      noncolligative absorption-inhibition mechanism. Many organisms have a
      heterogeneous suite of AFPs with variation in primary sequence between paralogous
      loci. Here, we demonstrate that the diversification of the AFP paralogues is
      promoted by positive Darwinian selection in two independently evolved AFPs from
      fish and beetle. First, we demonstrate an elevated rate of nonsynonymous
      substitutions compared to synonymous substitutions in the mature protein coding
      region. Second, we perform phylogeny-based tests of selection to demonstrate a
      subset of codons is subjected to positive selection. When mapped onto the three
      dimensional structure of the fish antifreeze type III antifreeze structure, these
      codons correspond to amino acid positions that surround but do not interrupt the
      putative ice-binding surface. The selective agent may be related to efficient
      binding to diverse ice surfaces or some other aspect of AFP function.

PMID- 11847567
TI  - Archaeal signal peptidases from the genus Thermoplasma: structural and
      mechanistic hybrids of the bacterial and eukaryal enzymes.

PMID- 11847568
TI  - The correct phylogenetic relationship of KdsA (3-deoxy-d-manno-octulosonate 8
      phosphate synthase) with one of two independently evolved classes of AroA (3
      deoxy-d-arabino-heptulosonate 7-phosphate synthase).

PMID- 11847570
TI  - Hepatocellular carcinoma and precancerous lesions: advances in imaging.

PMID- 11847571
TI  - Dysplastic nodules in liver cirrhosis: imaging.

PMID- 11847572
TI  - Hepatocellular carcinoma: harmonic ultrasound and contrast agent.

PMID- 11847573
TI  - Hepatocellular carcinoma: multidetector row helical CT.

PMID- 11847574
TI  - Intra- and perinodular hemodynamics of hepatocellular carcinoma: CT observation
      during intra-arterial contrast injection.

PMID- 11847575
TI  - Hepatocellular carcinoma: contrast-enhanced MRI.

PMID- 11847576
TI  - Hepatocellular carcinoma: evaluation of therapeutic response to interventional
      procedures.

PMID- 11847577
TI  - Hepatic angiomyolipoma: radiologic and histopathologic correlation.
AB  - We present two cases of hepatic angiomyolipoma. Histologic analysis showed that
      mature adipose tissue occupied 79.0% of the area on the largest cut surface in
      the first case and 40.2% in the second case. We suggest that the difference in
      the ratio of adipose tissue volume to its distribution is reflected on diagnostic
      images.

PMID- 11847578
TI  - Angiomyolipoma of the liver with least amount of fat component: imaging features
      of CT, MR, and angiography.
AB  - We report two cases of angiomyolipoma of the liver, where small amounts of fat on
      computed tomography, magnetic resonance imaging, and angiography made
      distinguishing this tumor from other hypervascular tumors difficult. Recognizing
      the imaging features of no capsule, hypervascularity of the tumor including the
      fat component, and early venous drainage may be helpful for correctly diagnosing
      angiomyolipoma of the liver.

PMID- 11847579
TI  - Acute fulminant hepatic infection causing fatal "emphysematous hepatitis": case
      report.
AB  - We describe a case of fatal fulminant hepatic infection with gas replacement of
      the hepatic parenchyma and no evidence of a liquified abscess in a diabetic
      patient: a case of "emphysematous hepatitis," the hepatic equivalent of
      emphysematous pyelonephritis. Computed tomography and clinical findings are
      described.

PMID- 11847580
TI  - Emphysematous cholecystitis: sonographic findings.
AB  - BACKGROUND: Emphysematous cholecystitis (EC) is a rare but life-threatening
      complication of acute cholecystitis, and an early diagnosis is required to
      prevent delay in patient management. Because sonography (US) is the first choice
      for diagnosing gallbladder diseases, US findings of EC should be understood more
      precisely. METHODS: We reviewed US findings of 11 surgically proven cases of EC
      (with small amounts of gas in three cases and large amounts in eight cases) and
      compared those with patients' clinical data. RESULTS: (1) In cases with small
      amounts of gas, US showed an echogenic line with a distinct ring-down artifact or
      a "powder snow-like" speckled posterior echo. (2) In cases with large amounts of
      gas, US showed a wide spiculated echogenic band with a powder snow-like speckled
      posterior echo or a speckled acoustic shadowing. In all cases, the presence of
      gas prevented visualization of the gallbladder wall. (3) US did not differentiate
      gas localized to the gallbladder wall and gas extending to the surrounding
      hepatic tissue. (4) Two diabetic cases showed gas throughout the intrahepatic
      bile ducts. In those cases, the time from diagnosis to recovery was relatively
      long. CONCLUSION: Our series showed some characteristic US patterns of EC. A good
      understanding of its US findings and appropriate emergent management will reduce
      the serious morbidity and mortality rates caused by EC.

PMID- 11847581
TI  - Sinusoidal spread of liver metastases from renal cell carcinoma: simulation of
      diffuse liver disease on MR imaging.
AB  - Rarely, hepatic metastases can simulate hepatic infiltrative diseases. We present
      a case of a patient with advanced metastatic renal cell carcinoma who developed
      hepatomegaly and clinical signs of hepatocellular injury. On magnetic resonance
      imaging, the injury simulated a diffuse process, e.g., acute fulminant viral or
      chemical hepatitis or drug toxicity. Despite its high resolution, magnetic
      resonance imaging might not depict focal lesions in patients with extensive
      metastases. In correlation with clinical history, malignant disease should be
      considered when diffusely abnormal hepatic signal intensity is noted.

PMID- 11847582
TI  - Imaging evaluation of posttraumatic renal injuries.
AB  - Computed tomography plays an important role for the evaluation of most patients
      with suspected renal injury after trauma. Intravenous urography is used for gross
      assessment of renal function in hemodynamically unstable patients. Renal injuries
      can be classified into four large groups: (1) minor renal contusion, lacerations,
      subcapsular hematoma, and small cortical infarcts; (2) major renal lacerations
      extending to the medulla with or without involvement of the collecting system;
      (3) catastrophic renal injuries including fragmentation of the kidney and renal
      pedicle vascular injuries; and (4) ureteropelvic junction injuries. Integration
      of the imaging findings of renal injury with clinical information is important to
      developing a treatment plan.

PMID- 11847583
TI  - Renal involvement by Rosai-Dorfman disease: CT findings.
AB  - Rosai-Dorfman disease is a rare disease characterized histologically by
      proliferation of histiocytes and has clinical features suggestive of a
      lymphomalike disease. Lymph nodes and extranodal sites might be involved, but
      renal involvement is rare. We present computed tomographic findings in three
      cases of renal involvement by Rosai-Dorfman disease. Two cases showed renal hilar
      masses and one case showed subcapsular hypodense infiltration. Renal involvement
      by Rosai-Dorfman disease has a characteristic appearance and should be included
      in the differential diagnosis of renal hilar masses or subcapsular hypodense
      infiltration.

PMID- 11847584
TI  - Fibroepithelial polyps of the urinary tract.
AB  - BACKGROUND: Fibroepithelial polyps of the urothelium are rare but frequently
      mistaken for transitional cell carcinoma. To better define the demographics,
      urothelial distribution, and typical gross anatomic and radiologic appearances,
      we reviewed 41 pathologically proven cases. METHODS: We reviewed 41 cases of
      fibroepithelial polyps from the archives of the Armed Forces of Pathology. Data
      were collected from radiographic studies, gross anatomic pathology, and pathology
      and radiology reports and categorized by age, sex, clinical presentation, lesion
      size, location, and morphology. RESULTS: The mean patient age was 21 years, and
      58% were male. Most presented with hematuria and/or flank pain (68%). Most polyps
      were located in the upper ureter or renal pelvis (87%). Posterior urethral and
      bladder polyps were present in children. Most polyps were single or bilobed (73%)
      and 1-6 cm. CONCLUSION: Because most urothelial tumors are malignant epithelial
      tumors, fibroepithelial polyps are commonly mistaken for transitional cell
      carcinomas. However, because fibroepithelial polyps and malignant urothelial
      tumors typically present in different patient populations, different locations in
      the urinary tract, and appear different radiographically, distinguishing features
      between these entities is helpful in determining the differential diagnosis of a
      urothelial mass. In the appropriate clinical setting, fibroepithelial polyps
      should be considered in the differential diagnosis, which will affect surgical
      treatment.

PMID- 11847586
TI  - Animal models of postinfectious obesity: hypothesis and review.

PMID- 11847585
TI  - CT demonstration of a rapidly growing transitional cell carcinoma of the ureter
      and renal pelvis.
AB  - Transitional cell carcinoma (TCC) is the most common urothelial malignancy. We
      present a case of an exceptionally aggressive TCC involving the renal pelvis and
      ureter. To our knowledge, an upper tract TCC of such rapid growth has not been
      reported.

PMID- 11847587
TI  - Comparison of the neuropathogenicity of two SSPE sibling viruses of the Osaka-2
      strain isolated with Vero and B95a cells.
AB  - Two sibling viruses, Fr/V and Fr/B, of the subacute sclerosing panencephalitis
      (SSPE) virus Osaka-2 strain were isolated from a small biopsy specimen of the
      brain of an SSPE patient by cocultivation with two different cell lines, Vero and
      B95a cells, respectively. These two sibling viruses differ from each other in
      their molecular mechanisms of defective M protein expression. In this study, we
      found that the Fr/B virus could scarcely form syncytium foci on Vero cells,
      although the Fr/V virus could do so on both Vero and B95a cells, showing a
      similar relation of cell tropism between recent field isolates and laboratory
      strains of the measles virus. Severe neurovirulence of both Fr/V and Fr/B viruses
      was observed in hamsters inoculated intracerebrally with less than 100 PFU, in
      contrast to the negative neurological and pathological findings in hamsters
      inoculated even with more than 10(5) PFU of their possible progenitor measles
      virus. Comparative sequence analysis of inoculated viruses and reisolated viruses
      from diseased hamster brains showed few variations at a region containing the P-M
      gene junction, indicating that the inoculated viruses propagated in the brains
      and induced neurovirulence. All these results suggest that SSPE virus isolated
      with a lymphoid cell line is similar in neuropathogenicity to that isolated with
      a nonlymphoid cell lines, irrespective of differences in the molecular mechanism
      of M protein defectiveness.

PMID- 11847588
TI  - Expression of brain-derived neurotrophic factor in the central nervous system of
      mice using a poliovirus-based vector.
AB  - Brain-derived neurotrophic factor (BDNF) is a promising candidate for the gene
      therapy of neurological disease. To deliver BDNF to neurons of the central
      nervous system (CNS), a nucleotide sequence encoding the mature peptide of BDNF
      was inserted into the genome of poliovirus, a neurotropic virus that is known to
      replicate mainly in motor neurons of the spinal cord of the CNS. Thus, the
      recombinant poliovirus constructed was replication-competent. The expression of
      BDNF in cultured cells infected with the recombinant poliovirus was evident when
      the cells were analyzed using an immunofluorescence assay and Western blotting.
      When the recombinant viruses were injected intramuscularly into transgenic mice
      that carry the human poliovirus receptor gene, the antigens of poliovirus and
      BDNF were detected in the motor neurons of the spinal cord at 3 days
      postinfection, and had disappeared by 7 days postinfection. This study suggests
      that poliovirus can be used as a virus vector for the delivery of neurotrophic
      factors to the motor neurons of the central nervous system and may provide a new
      approach for the treatment of motor neuron diseases.

PMID- 11847589
TI  - Infection of human oligodendroglioma cells by a recombinant measles virus
      expressing enhanced green fluorescent protein.
AB  - One of the hallmarks of the human CNS disease subacute sclerosing panencephalitis
      (SSPE) is a high level of measles virus (MV) infection of oligodendrocytes. It is
      therefore surprising that there is only one previous report of MV infection of
      rat oligodendrocytes in culture and no reports of human oligodendrocyte infection
      in culture. In an attempt to develop a model system to study MV infection of
      oligodendrocytes, time-lapse confocal microscopy, immunocytochemistry, and
      electron microscopy (EM) were used to study infection of the human
      oligodendroglioma cell line, MO3.13. A rat oligodendrocyte cell line, OLN-93, was
      also studied as a control. MO3.13 cells were shown to be highly susceptible to MV
      infection and virus budding was observed from the surface of infected MO3.13
      cells by EM. Analysis of the infection in real time and by immunocytochemistry
      revealed that virus spread occurred by cell-to-cell fusion and was also
      facilitated by virus transport in cell processes. MO3.13 cells were shown to
      express CD46, a MV receptor, but were negative for the recently discovered MV
      receptor, signaling leucocyte activation molecule (SLAM). Immunohistochemical
      studies on SSPE tissue sections demonstrated that CD46 was also expressed on
      populations of human oligodendrocytes. SLAM expression was not detected on
      oligodendrocytes. These studies, which are the first to show MV infection of
      human oligodendrocytes in culture, show that the cells are highly susceptible to
      MV infection and this model cell line has been used to further our understanding
      of MV spread in the CNS.

PMID- 11847590
TI  - Prophylactic and therapeutic effects of human immunoglobulin on the pathobiology
      of HSV-1 infection, latency, and reactivation in mice.
AB  - Pooled human immunoglobulin (IgG) was evaluated as prophylaxis and treatment of
      HSV-1 infection in mice. We compared the effects of IgG on the course of acute
      infection and spread of virus through the nervous system, as well as on the
      establishment, maintenance, and reactivation of virus from latency. Balb/c mice
      received a single 3.75 mg intraperitoneal injection of IgG 24 h before or 24 h,
      48 h, or 72 h after ocular infection with 10(6) pfu of HSV-1 strain McKrae.
      Treatment with IgG protected against death in a time-dependent manner (P < 0.001
      for -24 h vs. +48 h and +72 h IgG treatment groups). Viral shedding from the eyes
      was reduced more in mice treated with IgG at -24 h or +24 h relative to animals
      treated at +48 h. Viral titers in the eyes were reduced in mice treated with IgG
      at +24 h, but not at +48 h. In ganglia, virus recovery was reduced (P < 0.05) in
      mice treated at -24 h, +24 h, or +48 h relative to untreated mice, or ones
      treated at +72 h. In brains, similar results were observed in mice treated at -24
      h, +24 h, or +48 h relative to +72 h. Upon explantation, virus reactivated from
      all ganglia of all surviving mice regardless of treatment group. DNA quantitation
      showed that mice pretreated with IgG tended towards lower quantities of latent
      genome copies compared to +24 h treatment and +48 h treatment. UV irradiation
      induced reactivation in vivo in 16/40 pretreated mice, 20/29 mice treated at +24
      h, and in 8/8 mice treated at +48 h (P = 0.03 and P = 0.004, for comparisons at 
      24 h vs. +24 h, and -24 h vs. +48 h, respectively). Histopathological studies
      revealed that mice pretreated and treated with IgG had milder encephalitis and
      reduced virus spread compared to untreated mice. Pooled human IgG attenuates the
      spread of, and morbidity from, HSV-1 if given before and within 2 days after
      ocular infection.

PMID- 11847592
TI  - Selected cytotoxic T lymphocytes with high specificity for HTLV-I in
      cerebrospinal fluid from a HAM/TSP patient.
AB  - Human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic
      paraparesis (HAM/TSP) is a chronic inflammatory disease of the spinal cord in
      which HTLV-I Tax-specific cytotoxic T lymphocytes (CTL) have been suggested to be
      immunopathogenic. However, it is unknown whether the HTLV-I-specific CTL in the
      central nervous system differ from those in the periphery. We investigated
      functional T-cell receptor diversity in HTLV-I Tax11-19-specific CTL clones
      derived from peripheral blood and cerebrospinal fluid (CSF) of a HAM/TSP patient
      using analogue peptides of the viral antigen. CTL responses to the analogue
      peptides varied between T-cell clones, however, CTL clones from CSF showed
      limited recognition of the peptides when compared to those from peripheral blood.
      This suggests that CTL with highly focused specificity for HTLV-I Tax accumulate
      in the CSF and may contribute to the pathogenesis of HAM/TSP. Furthermore, this
      study provides a rationale for analogue peptide-based immunotherapeutic
      strategies focusing on the immunopathogenic T-cells in HTLV-I-associated
      neurologic disease.

PMID- 11847591
TI  - Rinderpest and peste des petits ruminants viruses exhibit neurovirulence in mice.
AB  - Members of the morbillivirus genus, canine distemper (CDV), phocine distemper
      virus (PDV), and the cetacean viruses of dolphins and porpoises exhibit high
      levels of CNS infection in their natural hosts. CNS complications are rare for
      measles virus (MV) and are not associated with rinderpest virus (RPV) and peste
      des petits ruminants virus (PPRV) infection. However, it is possible that all
      morbilliviruses infect the CNS but in some hosts are rapidly cleared by the
      immune response. In this study, we assessed whether RPV and PPRV have the
      potential to be neurovirulent. We describe the outcome of infection, of selected
      mouse strains, with isolates of RPV, PPRV, PDV, porpoise morbillivirus (PMV),
      dolphin morbillivirus (DMV), and a wild-type strain of MV. In the case of RPV
      virus, strains with different passage histories have been examined. The results
      of experiments with these viruses were compared with those using neuroadapted and
      vaccine strains of MV, which acted as positive and negative controls
      respectively. Intracerebral inoculation with RPV (Saudi/81) and PPRV
      (Nigeria75/1) strains produced infection in Balb/C and Cd1, but not C57 suckling
      mice, whereas the CAM/RB rodent-adapted strain of MV infected all three strains
      of mice. Weanling mice were only infected by CAM/RB. Intranasal and
      intraperitoneal inoculation failed to produce infection with any virus strains.
      We have shown that, both RPV and PPRV, in common with other morbilliviruses are
      neurovirulent in a permissive system. Transient infection of the CNS of cattle
      and goats with RPV and PPRV, respectively, remains a possibility, which could
      provide relevant models for the initial stages of MV infection in humans.

PMID- 11847593
TI  - Lack of nitric oxide synthase type 2 (NOS2) results in reduced neuronal apoptosis
      and mortality following mouse hepatitis virus infection of the central nervous
      system.
AB  - The role of nitric oxide synthase type-2 (NOS2)-derived nitric oxide (NO) in the
      pathogenesis of mouse hepatitis virus (MHV)-induced central nervous system
      disease was examined. Infection of NOS2 knockout ((-/-)) and NOS2(+/+) mice with
      MHV resulted in similar kinetics of viral clearance from the brain and comparable
      levels of demyelination. MHV-infected NOS2(-/-) mice displayed a marked decrease
      in mortality as compared to infected NOS2(+/+) mice that correlated with a
      significant decrease (P < or = 0.001) in the number of apoptotic cells
      (determined by TUNEL staining) present in the brain. Confocal microscopy revealed
      that the majority of cells (>70%) undergoing apoptosis were neurons. These
      studies indicate that NOS2-generated NO contributes to apoptosis of neurons but
      not demyelination following MHV infection.

PMID- 11847594
TI  - HTLV-I-associated myelopathy: are ferritin, S100beta protein, or guanine
      nucleotides CSF markers of disease?
AB  - In southern Brazil, there is an endemic high prevalence foci of HTLV-I and HTLV
      II infection. HTLV-infected individuals may develop HAM/TSP. Little is known
      about HAM/TSP pathogenesis and there is a lack of disease progression markers.
      This study investigated ferritin, S-100beta protein, and guanine nucleotides (GN)
      concentrations in the CSF of 18 patients with HAM/TSP. In HAM/TSP patients,
      concentrations of ferritin and S100beta were increased, whereas GMP was reduced.
      CSF ferritin, S100beta, and GN are potential markers for HAM/TSP.

PMID- 11847595
TI  - Sutured coronary artery grafting utilizing the Heartflo anastomosis device--first
      clinical experiences.
AB  - BACKGROUND: The Heartflo device was developed to facilitate consistency in distal
      coronary anastomosis quality. The device automates the suturing process during
      the anastomosis procedure via simultaneous delivery of ten standard 7-0
      polypropylene sutures through the graft and the coronary vessel wall. METHODS: In
      30 elective coronary artery bypass patients, one distal anastomosis was
      intentionally performed with the anastomosis device. Device success was stated if
      a patent anastomosis with a minimal flow of 50 ml/min resulted, additional
      stitches were counted if bleeding occurred. RESULTS: 4 cases of device failure
      occurred in the first 5 patients. The subsequent patients were operated without
      any mechanical problems. In 16 patients (53 %), a patent anastomosis with a mean
      flow of 75 +/- 6 ml/min using 1.7 +/- 0.3 additional stitches was achieved.
      Anastomoses were completed in 19.0 +/- 0.7 min; postoperative course was
      uneventful in all patients. CONCLUSIONS: We have shown that coronary anastomoses
      are feasible using the Heartflo device, representing a promising step on the way
      to automated coronary anastomoses. Its application is still limited by the size
      and tissue quality of the target vessel and difficult suture management during
      the anastomosis procedure.

PMID- 11847596
TI  - Cardiopulmonary bypass copolymer surface modification reduces neither blood loss
      nor transfusions in coronary artery surgery.
AB  - OBJECTIVE: Surface-modifying additives (SMA) have been suggested for improving
      cardiopulmonary bypass (CPB) circuit biocompatibility, potentially minimizing
      inflammatory complications and bleeding associated with CPB. The purpose of this
      prospective, randomized clinical study was to compare a novel copolymer surface
      modified CPB circuit (SMARXT; COBE Cardiovascular) against the unmodified
      circuit. METHODS: We randomized 122 patients with isolated coronary artery
      disease subjected to first-time surgery on CPB into either the SMA (n = 62) or
      the control group (n = 60). Exclusion criteria included renal insufficiency,
      liver disease, coagulopathy, anticoagulation therapy < 6 days preop, carotid
      artery stenosis > 70 %, and a history of stroke. We collected perioperative
      clinical data including drainage blood loss, transfusion requirements, duration
      of mechanical ventilation, and ICU stay. Platelet function was determined pre-
      and post-CPB. RESULTS: SMA patients received 3.2 +/- 0.9 (SD) grafts during 48 +/
      16 min of aortic cross clamp and 91 +/- 30 min CPB (Control: 3.0 +/- 0.9 grafts;
      p = 0.33, 46 +/- 14 min AXC; p = 0.36, and 84 +/- 23 min CPB; p = 0.14). In the
      SMA group, 23 patients (37 %) received red blood-cell transfusions, 9 patients
      (15 %) fresh frozen plasma, and 3 patients (5 %) received platelets (control: n =
      27 [46 %], p = 0.44; n = 10 [17 %], p = 0.91; and n=4 [7 %], p = 0.71,
      respectively). Platelet count on CPB fell to the same level in both groups. In
      SMA patients, platelet function decreased from 94.2 +/- 24.9 % pre-CPB to 79.5 +/
      32.8 % post-CPB (p = 0.043) (control: from 87.7 +/- 25.6 % to 69.4 +/- 34.7 %; p
      = 0.001). Postoperative drainage blood loss, mechanical ventilation duration, and
      ICU stay were similar in both groups (p > 0.3). One patient of the control group
      was excluded due to surgical bleeding, and one SMA patient died. CONCLUSIONS: Our
      results show that the surface-modified CPB circuit decreased neither blood loss
      nor transfusions despite slightly better platelet function preservation compared
      to the unmodified circuit. This type of CPB circuit surface modification does not
      appear to improve clinical outcome in low-risk coronary artery surgery patients.

PMID- 11847597
TI  - The effects of L-carnitine on spinal cord ischemia/reperfusion injury in rabbits.
AB  - BACKGROUND: Paraplegia after distal aortic aneurysm repair remains a persistent
      clinical problem. We hypothesized that the tolerance of the spinal cord to an
      ischemic period could be improved with hypothermic Ringer's Lactate containing L
      Carnitine. MATERIALS AND METHODS: Twenty-eight New Zealand white rabbits were
      used as spinal cord ischemia models. We separated rabbits into four equal groups
      and clamped each animal's abdominal aorta distal to the left renal artery. We
      occluded the aortas above the iliac bifurcation for 30 minutes. In group I, the
      infrarenal aorta was clamped without infusing any solution. In group II, Ringer's
      Lactate solution was infused at + 25degrees C for 3 minutes at a rate of 5 ml/min
      into the isolated aortic segments immediately after cross-clamping and the last 3
      minutes of ischemia. In group III, Ringer's Lactate solution at +3 degrees C was
      given in the same method as that of group II. In group IV, Ringer's Lactate
      solution at +3 degrees C plus 100 mg/kg of L-carnitine was infused using the same
      technique. We assessed the neurological status of the hind limbs 24 and 48 hours
      after operation according to Tarlov's criteria. All animals were sacrificed and
      spinal cords were harvested for histological analyses. RESULTS: The neurological
      status in groups III and IV was significantly superior to that of groups I and
      II. All the animals in group I had complete hind-limb paraplegia. Complete hind
      limb paraplegia occurred in 5 rabbits in group II. Two of the 7 animals in group
      III had spastic paraplegia, and none at all in group IV. Histological analysis of
      the cross-clamped segments of the rabbits with paraplegia in group I, II and III
      revealed changes consistent with ischemic injury, while findings were normal for
      the normal animals in group III and IV. CONCLUSIONS: In this model, the infusion
      of hypothermic Ringer's Lactate contained L-carnitine provided sufficient spinal
      cord protection against ischemia. Clinically, this may be a useful adjunct for
      prevention of paraplegia during surgery of the descending aorta.

PMID- 11847598
TI  - Right ventricular performance during left ventricular unloading conditions: the
      contribution of the right ventricular free wall.
AB  - AIM: Right ventricular (RV) dysfunction is a significant complication following
      implantation of left ventricular assist device (LVAD). However, RV performance
      after LVAD implantation remains unclear. We have studied the effects of preload
      and afterload on RV performance under left ventricular (LV) unloading. METHODS:
      Six adult mongrel dogs were subjected to cardiopulmonary bypass. RV preload and
      afterload were independently regulated. Dynamic pressure-length analysis of RV
      free walls was performed using micromanometer catheter and sonomicrometric
      dimension transducers. Global RV systolic function was evaluated by the
      relationship between stroke volume vs. end-diastolic length (EDL) or end
      diastolic pressure (EDP). We also examined the afterload dependency of RV
      performance at constant stroke volume. RESULTS: Stroke volume vs. EDP and stroke
      volume vs. EDL demonstrated a linear relationship (r(2) = 0.849 +/- 0.147 and
      0.776 +/- 0.121, respectively). At constant stroke volume, RV systolic peak
      pressure vs. EDL or EDP were shown to have a linear relationship (r(2) = 0.906 +/
      0.050 vs. 0.909 +/- 0.047, respectively). CONCLUSION: The Frank-Starling
      relationship for RV performance was shown in this animal model. Without
      interventricular interaction, RV preload is dependent on RV afterload.

PMID- 11847599
TI  - Mid-term results of aortic valve preservation: remodelling vs. reimplantation.
AB  - OBJECTIVE: Valve-preserving root replacement has become an accepted alternative
      to composite replacement both in dissection and in aneurysmal disease. We
      retrospectively analysed 5-year results comparing root remodelling and
      reimplantation procedures. METHODS: From October 1995 to January 2001, 119
      patients underwent either root remodelling (group A; n = 98; age: 61 +/- 14
      years) or valve reimplantation within a vascular graft (group B; n = 21; age: 47
      +/- 17 years). In group A, 26 patients were operated for aortic dissection type A
      and 72 for aortic valve regurgitation and aneurysmal disease. In group B, 8
      patients were operated for aortic dissection type A, 13 for aortic valve
      regurgitation and aneurysm. Concomitant arch surgery was performed in 65 patients
      (group A: 57; group B: 8). RESULTS: Time on cardiopulmonary bypass was 121 +/- 30
      min in group A, 143 +/- 24 min in group B, and aortic cross-clamp time was 87 +/-
      19 min in group A and 113 +/- 24 min in group B. Average duration was therefore
      longer in group B (p = n.s.) Hospital mortality was 3.1 % in group A and 0 % in
      group B. Following elective procedures, hospital mortality was 1.1 % in group A.
      Freedom from aortic regurgitation over grade 2 at 4 years was 86 % in group A and
      94.7 % in group B. At 4 years, freedom from proximal reoperation was 97.8 % in
      group A and 100 % in group B. There was no deterioration of valve function or
      need for reoperation observed after 1 year in either group. CONCLUSION: Five-year
      results are comparable and encouraging for remodelling and reimplantation
      procedures. If the initial valve function and geometry is adequate, the chance of
      secondary failure beyond the first year is minimal.

PMID- 11847600
TI  - Continuous antegrade blood cardioplegia: cold vs. tepid.
AB  - BACKGROUND: Continuous antegrade blood cardioplegia (CABCP) is used at different
      temperatures. We investigated the consequences of CABCP at 6 degrees C (COLD) vs.
      28 degrees C (TEPID). METHODS: Anesthetized open-chest pigs (25 +/- 2 kg) were
      placed on cardiopulmonary bypass (CPB). The hearts were arrested for 30 min by 6
      degrees C cold or 28 degrees C tepid CABCP (n = 8 each). After an initial 3 min
      antegrade application of high potassium (20 mEq) cold (6 degrees C) blood
      cardioplegia, the hearts were arrested for a subsequent 27 min by normokalemic
      blood delivered antegrade at either 6 degrees C or 28 degrees C. After this, the
      hearts underwent perfusion with warm systemic blood for an additional 30 min on
      CPB. Biochemical cardiac data (MVO2 [ml/min/100 g], release of creatine kinase
      [CK U/min/100 g] and lactate [mg/min/100 g]) were measured during CPB. Total
      tissue water content (%) and left ventricular stroke work index (SWI g x m/kg)
      were determined 30 min after discontinuation of CPB and compared to pre-CPB
      controls. RESULTS: Cold CABCP kept all hearts continuously arrested. The COLD
      hearts showed no biochemical or functional disturbance. The TEPID hearts
      intermittently fibrillated and required additional high potassium BCP shots. The
      TEPID hearts showed a marked CK leakage (2.6 +/- 0.4 vs. 0.7 +/- 0.4), lactate
      production (4.0 +/- 1.6 vs. extraction from the COLD group) despite the non
      ischemic protocol, an impaired initial oxygen consumption (4.2 +/- 1.3 vs. 7.1 +/
      1.6) at the end of cardiac arrest, the formation of myocardial edema (79.5 +/-
      1.0 vs. 77.0 +/- 0.8), and a depressed recovery of SWI (0.69 +/- 0.15 degrees vs.
      1.41 +/- 0.13). *p < 0.05 for comparison of TEPID vs. COLD hearts using Student's
      t-test for unpaired data; degrees p < 0.05 for intergroup-comparison of TEPID vs.
      COLD vs. controls using ANOVA adjusted for repeated measures. CONCLUSIONS:
      Uninterrupted cardioplegia can be safely performed with cold normokalemic CABCP.
      In contrast, tepid normokalemic CABCP leads to fibrillation, jeopardizes the
      heart, and should be avoided.UND

PMID- 11847601
TI  - Coronary artery revascularization using both ITAs as free conduits in patients
      with three-vessel disease--the lambda graft.
AB  - BACKGROUND: There is little information on using internal thoracic arteries (ITA)
      as free conduits in coronary artery bypass grafting. This study examines the
      results using both ITAs as free grafts in a lambda configuration implanting the
      common trunk into the ascending aorta. METHODS: Over a 6-year period, 317
      patients underwent coronary artery revascularization with both ITAs as free
      grafts in a lambda configuration. RESULTS: An average of 4.9 distal anastomoses
      per patient was performed. There were 4 deaths (three early and one late). The
      mean NYHA class improved from preoperatively 2.8 to 1.1 at the last check. All 16
      patients with suspected recurrent angina or a pathologic exercise test were
      restudied by angiography. Segmental graft stenosis or occlusion was found in 13
      (in only one at aortic anastomosis). Five patients underwent late PTCA, and two
      underwent coronary reoperation. The six-year actuarial survival was 98% (90 %
      CL+/- 2 %), intervention-free survival 96 % (90 % CL +/- 2 %). CONCLUSION:
      Revascularization using both ITAs as free grafts in a lambda configuration gives
      good early and mid-term results for up to 6 years. The aortic ITA anastomosis can
      be considered safe.

PMID- 11847602
TI  - Five-year experience with valve sparing surgery for aortic root aneurysms.
AB  - BACKGROUND: The aim of this study was to analyze the mid-term results of aortic
      root reconstruction. METHODS: Between September 1995 and March 2001, 32 patients
      (25 males, 7 females, median age 58 +/- 21 years) underwent aortic root
      reconstruction as described by T. David. Indications for operation were aortic
      insufficiency with ascending aortic aneurysm in 27 patients, and acute aortic
      dissection (Stanford type A) in 5 patients. In all patients the native valve was
      preserved and suspended inside a tubular prosthesis with reimplantation of the
      coronary arteries. In 10 patients the classic reconstruction technique was
      modified by shaping a "Neosinus." RESULTS: There was one perioperative death due
      to myocardial infarction. Two patients suffered a stroke. 26 patients were
      followed up 12 months postoperatively. 22 out of 26 patients were in NYHA
      functional class I, 2 patients in class II and the remaining 2 in class III.
      Three patients died in the postoperative period. Six patients had trivial AR, 4
      mild and 1 moderate regurgitation. There were no thromboembolic events during
      follow up. The mean transvalvular gradient was 3.5 +/- 2.2 mmHg. Compared to a
      normal cohort of patients (n = 20), resuspended aortic valves opened (26.4 +/-
      5.8 vs. 61.3 +/- 22.1 cm/sec, p < 0.0001) and closed (22.8+/- 6.9 vs. 57.9 +/-
      22.3) at a higher speeds and also showed shorter opening (0.053 +/- 0.12 vs.
      0.023 +/- 0.09 sec, p < 0.0001) and closing times (0.051 +/- 0.07 vs. 0.23 +/-
      0.07 cm/sec) of the aortic leaflets. CONCLUSIONS: Aortic valve reimplantation is
      a reliable technique able to reduce long term complications when compared to
      conventional composite graft replacement of the aortic root. Altered leaflet
      opening and closing dynamics do not impair midterm durability.

PMID- 11847603
TI  - Fate of intramural coronary arteries after arterial switch operation.
AB  - BACKGROUND: To evaluate the impact of intramural coronary arteries for the peri-,
      postoperative and long-term course after arterial switch operation (ASO).
      METHODS: ASO was performed in 351 patients between 1981 and 2000 with
      dextrotransposition of the great arteries (d-TGA). Five patients (1.4 %) had an
      intramural coronary artery. Coronary transfer was performed with a collar under
      dissection of the commissure without longitudinal splitting of the intramural
      section. RESULTS: None of these patients died; the intraoperative course was
      uneventful, and no myocardial ischemic changes were observed. In three patients,
      follow-up cardiac catheterization after 5, 16 and 53 months revealed an occlusion
      of the intramural coronary ostium. Exercise electrocardiography and myocardial
      scintiscan showed myocardial ischemia. Two of these patients underwent a
      successful internal mammary artery bypass. CONCLUSIONS: The intramural course of
      coronary arteries in patients with d-TGA is rare and does not cause increased
      mortality or myocardial infarction rates. However, the risk of coronary occlusion
      over time seems to be high. Therefore, patients with this condition require
      selective coronary angiography and frequent exercise investigations.
      Revascularization with an internal mammary artery bypass may be indicated.

PMID- 11847604
TI  - Transfection of E-cadherin cDNA in human lung tumor cells reduces invasive
      potential of tumors.
AB  - Lung cancer is a major health-care problem in industrialized countries. With
      reference to its therapeutic consequences and major histological variations, it
      is divided into two subgroups - SCLC (small-cell lung cancer) and NSCLC (non
      small-cell lung cancer). As an important factor of cell-cell and cell-substratum
      interaction, cell adhesion molecules (CAMs) seem to play a key role in tumor-cell
      migration and invasion that lead to metastases. We investigated human lung tumor
      cell lines established from histologically documented neoplastic lesions taken in
      our operating theater. Immunohistological screening showed differences in E
      cadherin expression with no clear predominance of SCLC or NSCLC cell lines. Using
      an invasion model with Matrigel Matrix and a migration assay, we could
      demonstrate a more aggressive behavior pattern in E-cadherin-negative cell lines.
      We transfected E-cadherin cDNA into a formerly negative cell line showing strong
      invasive behavior in the initial tests in order to investigate the role of E
      cadherin in this process. In this study, we examined E-cadherin cDNA transfection
      in human bronchial carcinoma cells. At present, transfection is stable with a
      follow-up time of one year. We could demonstrate that cell lines were remarkably
      less invasive after transfection of E-cadherin in the invasion model with
      Matrigel Matrix. These results indicate that the E-cadherin CAM plays an
      important role in lung tumor invasion and metastasis. Further studies are in
      progress to confirm these findings and to describe a possible role of this CAM in
      tumor therapy.

PMID- 11847605
TI  - Effects of trifluoperazine on the contraction kinetics of the isolated intact
      tracheal and pulmonary artery smooth muscle.
AB  - BACKGROUND: We studied the effect of the calmodulin antagonist trifluoperazine
      (TFP) on isolated intact rat tracheal and pulmonary artery smooth muscle
      contractile behaviour. METHODS: Experimental series: 1) TFP-dose-response curves
      for TFP's effect on force generation were constructed using rat tracheal smooth
      muscles and rat pulmonary artery preparations (n = 8). A concentration of 1
      micromol/l TFP was chosen for the subsequent experimental series. 2) Tracheas and
      pulmonary arteries (n = 14) were dissected in three segments. One of them was
      used immediately for experiments ("native"), the other two were treated for 12 h
      in 4 degrees C Tyrode solution without ("12 h cold storage") or with 1 micromol/l
      TFP ("12 h cold storage + TFP"). These preparations contracted after supramaximal
      effective electrical field stimulation. The force-clamping technique was used to
      analyse kinetic and mechanical parameters of smooth-muscle contraction in both
      types of preparation (measurement conditions: resting tension 2 mN, 37 degrees C,
      modified Krebs-Henseleit solution). RESULTS: 1) TFP decreased developed force
      dose-dependently in pulmonary artery and tracheal smooth muscle. 2) During
      sustained tonic activation, the contraction kinetics become slower both with and
      without TFP treatment (p < 0.0001). 3) TFP caused a dramatic retardation of the
      velocity of force generation in both types of preparation for any given time
      interval during the course of a tonic activation (p < 0.0005). 4) The dramatic
      effects of TFP on the contraction kinetics were not associated with effects on
      the extent of force generation. CONCLUSIONS: These results support the assumption
      that tracheal and pulmonary artery smooth muscle cross-bridge rates are
      controlled by a calcium-calmodulin-dependent myosin light chain kinase. This
      finding suggests the involvement of a calmodulin-independent regulator process
      responsible for the changes observed in the cross-bridge cycling rates during
      sustained tonic activation. A direct intervention on the contractile apparatus
      level is a measure for reduction of smooth-muscle tone without negative inotropic
      side effects.

PMID- 11847606
TI  - Prognostic factors and c-erbB-2 expression in non-small-cell lung carcinoma (c
      erbB-2 in non-small cell lung carcinoma).
AB  - The human proto-oncogene c-erbB-2/neu gene, which is structurally similar to the
      epidermal growth factor receptor gene, encodes a transmembrane protein of 185 kDa
      (p185) with tyrosine kinase activity. Paraffin-embedded sections from 42 cases
      with lung carcinoma were stained immunohistochemically using the Avidin-Biotin
      Horseradish Peroxidase method to search for c-erbB-2 reaction. Results were
      evaluated semiquantitatively. The c-erbB-2 expression from each case was compared
      according to tumor type, grade, mitotic activity, clinical stage and lymph node
      metastasis. Results were statistically analyzed by using chi-square tests. We
      were unable to detect a significant relation between c-erbB-2 expression and
      histological grade, nodal metastasis, number of mitotic figures or tumor type,
      but we did observe a statistically significant correlation between clinical stage
      and increased c-erbB-2 expression (p < 0.05). In our opinion, c-erbB-2 expression
      in human lung carcinomas may be useful for determining clinical outcome.

PMID- 11847607
TI  - Coexistence of non-Hodgkin's lymphoma and non-small cell lung carcinoma:
      diagnosis and treatment.
AB  - Abstract. In this communication, we will present a very rare case of the
      coexistence of non-Hodgkin's lymphoma (NHL; low malignant lymphocytic lymphoma of
      the B-cell type) and a non-small-cell lung carcinoma (NSCLC). A patient with a 15
      year history of NHL developed a generalized relapse of the lymphoma with an
      additional tumor mass in the left lower lobe of the lung. Bronchoscopy showed the
      evidence of the NHL. Due to non-responding chemotherapy on the lung tumor, the
      coexistence of a second malignancy was histologically proved in a second
      bronchoscopy. Resection of the lung tumor with complex lobectomy and
      lymphadenectomy was performed. After that, chemotherapy with four cycles of
      carboplatin supplemented with taxol was induced. The patient was discharged from
      the hospital with a stable remission of both tumor diseases. Restaging after six
      months showed no evidence of a tumor relapse. This is a very rare case of the
      coexistence of NHL and NSCLC; we will discuss the difficulty of diagnostic and
      treatment of both tumor diseases.

PMID- 11847608
TI  - Redo- extirpation of a cardiac leiomyosarcoma to avoid transplantation.
AB  - Cardiac leiomyosarcoma is a very rare entity that is found in less than 0.2 % of
      all cardiac tumors. At the time of primary diagnosis, it often shows advanced
      local invasion or may even be metastasized. Thus, complete resection can not
      easily be achieved. Cardiac transplantation has been reported as a therapeutic
      option. Here, we report on a case of a leiomyosarcoma reoccurrence arising 2
      years after initial surgery. We performed a radical redo-extirpation without the
      necessity of transplantation.

PMID- 11847609
TI  - Bronchial repair with pulmonary preservation for severe thoracic trauma.

PMID- 11847610
TI  - Association between human immunodeficiency virus and osteonecrosis of the femoral
      head.
AB  - The records of a consecutive series of 50 patients treated operatively for
      osteonecrosis of the femoral head were reviewed to determine the prevalence of
      human immunodeficiency virus (HIV) as an isolated risk factor for osteonecrosis.
      Twelve patients had a history of trauma to the hip and were excluded from the
      study. The remaining 38 patients were treated operatively for nontraumatic
      osteonecrosis of the femoral head. Of these, 7 patients were HIV positive, and 31
      were HIV negative. Of the 7 patients who were HIV positive, 4 (57%) had none of
      the known risk factors for osteonecrosis. Of the 31 patients who were HIV
      negative, 4 (13%) had none of the known risk factors for osteonecrosis. The
      difference between the groups was statistically significant, suggesting that HIV
      infection is a risk factor for the development of osteonecrosis of the femoral
      head.

PMID- 11847611
TI  - Impacted corticocancellous allografts and cement for revision of the femur
      component in total hip arthroplasty.
AB  - Revision of the femur component in total hip arthroplasty using impacted
      morcellized bone allografts and cemented Lubinus SP-II prosthesis or Charnley
      standard prosthesis was performed in patients with loss of bone stock grade II
      through IV according to the Endo-Klinik classification from 1st to 8th revision.
      We report the results from 57 hips in 56 patients, with a median of 64 months'
      follow-up. Modified Merle d'Aubigne-Postel postoperative scores increased
      significantly from preoperative to postoperative values for the Lubinus group and
      for the Charnley group. Few complications were seen in this follow-up period.
      Five stems had minor subsidence. Rate of mechanical failure was 4% for both
      groups. Radiologic examinations provided evidence of frequent trabecular
      remodeling of the graft, especially for the Lubinus prosthesis.

PMID- 11847612
TI  - Histology of impacted bone-graft incorporation.
AB  - We describe the histologic findings of 31 tissue samples from 21 cases in 19
      different patients taken 1 to 48 months after revision arthroplasty and impaction
      grafting in the hip (Lubinus SP-II prosthesis Waldemar Link, Hamburg, Germany, or
      Charnley Elite prosthesis, Johnson & Johnson, New Brunswick, NJ) and the knee
      (Link Rotation Knee Waldemar Link). One month after surgery, a fibrous stroma and
      some newly formed woven bone were found in the graft bed. After 4 months, many of
      the dead trabeculae in the graft bed had layers of living bone and osteoid in all
      samples. These layers, indicating a gradual ingrowth of living bone, increased
      over time. In the proximal end of the femur examined after 48 months, a
      significant proportion of the graft bone remained dead, whereas in the rest of
      the femur, the bone healing was complete. A similar but possibly less frequent
      bone formation was found in the 2 cases evaluated after a revision total knee
      arthroplasty combined with impaction grafting.

PMID- 11847613
TI  - Exchange impaction allografting for femoral revision hip arthroplasty: results in
      87 cases after 3.6 years' follow-up.
AB  - A total of 87 femoral exchange revision procedures were performed in 80 patients.
      Mean follow-up time was 3.6 years. Patients were followed prospectively. At
      follow-up, 5 patients had died, and 74 (93 %) completed follow-up. Results were
      evaluated on the basis of incidence of re-revisions and other complications,
      patient satisfaction, and preoperative and postoperative Harris hip score.
      Radiographic evaluation included preoperative femoral bone status evaluated
      according to Endo-Klinik and Mallory, incidence of subsidence, bone-graft
      incorporation, and signs of loosening. Three patients were re-revised, 2 patients
      suffered postoperative femoral fractures, 5 patients had hip dislocations, and 1
      patient suffered deep infection. Of patients, 90% expressed satisfaction with the
      result. Harris hip score improved from 39 to 82 (P <.001). Radiographically, only
      2 patients showed subsidence of >5 mm. Of patients, 88% showed signs of graft
      incorporation, and only 1 patient showed signs of loosening. Intermediate follow
      up evaluation of the exchange femoral revision technique showed good clinical and
      radiographic results. With a re-revision rate of 3.5% and incidence of >5 mm
      subsidence of 2.5%, we did not observe the problems of subsidence and femoral
      fractures that previous studies have described.

PMID- 11847614
TI  - Mortality, morbidity, and 1-year outcomes of primary elective total hip
      arthroplasty.
AB  - No representative data exist on the risks of adverse outcomes of total hip
      arthroplasty (THA) in the United Kingdom. A prospective observational study of
      unselected THA operations was carried out in 5 U.K. regions. Adverse outcomes
      were assessed from the hospital case notes and general practitioners of 1,100
      randomly selected patients and from 7,151 patient-completed questionnaires 3 and
      12 months after THA. Three-month mortality was 0.4% to 0.7%. Dislocation and
      thromboembolic complications were about 3% and 4%. Perioperative fracture,
      sciatic nerve palsy, aseptic loosening, and revision each had a risk of < or =
      1%. At 1 year, 2.6% of patients had undergone another operation on the same hip,
      11% reported moderate or severe pain in the operated hip, 23% had severe walking
      restriction, and 11% were dissatisfied with the operation. Patients and surgeons
      in the United Kingdom should have access to this information when making a
      decision about THA.

PMID- 11847615
TI  - Hydroxyapatite coating improves 8- to 10-year performance of the link RS
      cementless femoral stem.
AB  - In a prospective randomized clinical study, 12 hydroxyapatite (HA)-coated and 8
      identical but non-coated stems were implanted in 20 patients. At 8- to 10-year
      follow-up, the HA-coated stems displayed excellent clinical and radiographic
      results in 11 out of 12 patients, whereas 7 out of 8 non-coated stems were
      failures and had been subject to revision. Despite the small number of patients
      in this series, HA coating seems to improve the long-term stable fixation of
      uncemented femoral implants.

PMID- 11847616
TI  - Long-term follow-up of the GSB II total knee used in primary total knee
      arthroplasty.
AB  - The GSB II (Sulzer Medica, Winterthur, Switzerland) knee prosthesis ranks between
      the minimally constrained condylar prostheses and the fully constrained hinges.
      The senior author (T.R.S.) used this prosthesis in 47 patients (54 knees) with a
      maximum follow-up of 18 years (mean, 7.8 years). The mean patient age was 75
      years (range, 61-94 years). The 10- and 18-year cumulative life-table survival
      rates were 95.7% and 88.1% for prosthesis removal or infection, 87.4% and 76.8%
      for patient dissatisfaction, and 81.5% and 71.3% for Hospital for Special Surgery
      score <70 or infection (95% confidence interval). The cumulative rate of
      infection after 10 and 18 years was 4.3% and 11.6% based on the life-table
      survival analysis. The only indication for this type of prosthesis in a primary
      arthroplasty is a knee with severe deformity, bone loss, or ligament deficiency.

PMID- 11847617
TI  - Medium-term results of the ABG total hip arthroplasty in young patients.
AB  - A total of 66 patients (71 hips) <65 years old (average age, 55.4 years; range,
      26-65 years) received a proximally hydroxyapatite-coated femoral prosthesis with
      a hemispheric metal-backed, hydroxyapatite-coated acetabular cup (ABG hip,
      Howmedica International, Staines, UK), with an average follow-up of 4.8 years
      (range, 2-7 years). All operations were performed by 1 surgeon in a district
      general hospital. The average preoperative Harris hip score and Merle d'Aubigne
      score were 59.8 and 9.6, which rose to 92.7 and 16.3 at the longest follow-up.
      Most patients were satisfied with the outcome, with only 2 patients complaining
      of intermittent thigh pain. Survivorship analysis predicted a survival rate of
      96.87% at 7 years. There were 2 revisions, one to reposition an acetabular cup
      and one for an undersized femoral component. Radiographic changes were consistent
      with bone remodeling. There were no radiolucencies around the acetabular cup, but
      we noted eccentric polyethylene wear in 37 (60%) inserts ranging from 0.4 to 4 mm
      (annual wear average, 0.25 mm/y; range, 0.063-0.76 mm/y). There were no loose
      femoral stems. Osseointegration was achieved in all cases, with only 1 case
      developing endosteal cavitation in Gruen zone 2. Cancellous densification was
      found to be mainly in zones 2 and 6 (67.2% and 55.7%), extending distally in
      zones 3 and 5 (52.4% and 50.8%). Hypertrophy of the femoral shaft was less
      prominent and was noted mostly distally, in zones 3, 4, and 5 (11.4%, 18.3%, and
      18.3%), extending proximally in zones 2 and 6 (8.1% and 13.1%). The ABG hip can
      achieve excellent results in the medium term, but polyethylene wear of the
      acetabular insert should be noted with concern.

PMID- 11847618
TI  - Collarless polished tapered stem: clinical and radiological follow-up over 5
      years.
AB  - The clinical and radiologic outcome of a cemented, polished, tapered stem (CPT),
      implanted using contemporary cementing techniques in 108 consecutive operated
      hips in 100 patients (68 women and 32 men, aged 19 to 83 years at the time of
      surgery [mean, 65 years]) was assessed after >5 years. The Harris hip scores were
      good or excellent in 96% of the patients. Stem subsidence measured by the
      computer-assisted method described by Braud and Freeman was at a mean rate of
      0.44 mm/y, 1.08 mm during the first year, and stabilizing to a mean total of 2.18
      mm at >5 years. Subsidence was related inversely to the completeness of the
      cement mantle but did not correlate with the clinical or radiologic outcome. This
      study confirms that collarless, polished, tapered stems subside within the cement
      mantle but without loosening and that the CPT performs at least as well as the
      Exeter stem.

PMID- 11847619
TI  - Minimum 5-year follow-up and radiologic analysis of the all-polyethylene tibial
      component of the Kinemax Plus system.
AB  - All-polyethylene tibial components remain controversial. We report a series of
      249 cemented Kinemax Plus total knee arthroplasties using an all-polyethylene
      tibial component. After a minimum of 5 years, the median Knee Society pain, Knee
      Society function, and Hospital for Special Surgery Scores were 89, 60, and 83.5
      with 86% good or excellent results. The cumulative survival rate was 94.5% at 7
      years. Of tibial components, 38% had a radiolucent line, but only 1% had
      significant radiolucencies. The presence of a radiolucent line did not affect
      Knee Society or Hospital for Special Surgery scores adversely. This series is
      comparable to other series using either an all-polyethylene or a metal-backed
      tibial component. There currently is no good evidence that the experimentally
      superior metal-backed tibial components offer any advantage in practice.

PMID- 11847620
TI  - Early failure of the porous-coated anatomic cemented unicompartmental knee
      arthroplasty: A 5- to 9-year follow-up study.
AB  - This retrospective study analyzed the results of 26 porous-coated anatomic
      unicompartmental knee arthroplasties to determine the failure rate, the mode of
      failure, and the presentation of the failure. The mean follow-up was 6.9 years.
      All patients were assessed using the American and Oxford knee scores. The
      revision rate was 42%4, with a mean revision time of 38.4 months. The commonest
      presentation of failure included pain (100%), decreased mobility (75%), swelling
      (58%), and giving way (50%). The commonest modes of failure included femoral
      loosening (55%), polyethylene wear (55%), loosening and polyethylene wear (72%),
      and fracture-dislocation of the femoral prosthesis (18%). The 42% failure rate of
      the porous-coated anatomic unicompartmental knee arthroplasty necessitates
      regular surveillance and prompt revision, if failing, to avoid osteolysis.

PMID- 11847621
TI  - The influence of the posterior cruciate ligament in the maintenance of joint line
      in primary total knee arthroplasty: a radiologic study.
AB  - The aim of this study was to compare 2 total knee arthroplasty (TKA) designs
      radiologically to determine if a posterior cruciate ligament (PCL)-substituting
      design led to a built-in error of elevation of the joint line postoperatively.
      The restoration of the true joint line is a goal in primary TKA, although its
      effect on outcome has not been established fully. A total of 47 patients had 56
      TKAs performed by 2 surgeons using either the Howmedica Kinemax Plus (Rutherford,
      NJ) PCL-retaining or PCL-substituting TKAs. The patients were randomized to
      receive one of these designs, and the height of the joint line was assessed
      radiographically preoperatively and postoperatively. The joint line position
      preoperatively averaged 2.2 cm from the tibial tuberosity and postoperatively
      averaged 2.4 cm (PCL substituting) and 2.5 cm (PCL sparing). No difference in the
      thickness of the polyethylene insert used was seen with either design. The
      theoretical elevation of the joint line that occurs with the sacrifice of the PCL
      was not found to occur radiologically.

PMID- 11847623
TI  - Early failure of a press-fit carbon fiber hip prosthesis with a smooth surface.
AB  - We investigated a press-fit anatomically shaped hip stem made of carbon fiber
      reinforced composite material in a prospective clinical study. The intention of
      the design was that a surface of interlaced carbon fibers in the proximal part
      would achieve metaphyseal fixation. A total of 51 carbon stems were implanted in
      48 patients (30 women and 22 men). Mean age at operation was 59 years. The
      patients were followed clinically, radiologically, and with computed tomography.
      At 6-year follow-up, aseptic loosening was observed in 47 hips (92%). Forty stems
      were revised on average 30 months (range, 9-58 months) postoperatively. All
      revised carbon stems showed fibrous fixation without any bony on-growth. No
      osteolysis was seen. Histologically, no carbon wear or inflammatory reactions
      were observed. Only 4 cases had a good clinical result with bony fixation on
      computed tomography scan. The carbon fiber prosthesis without effective ingrowth
      or on-growth irregularities showed a high rate of early loosening.

PMID- 11847622
TI  - In vivo comparison of femorotibial contact positions for press-fit posterior
      stabilized and posterior cruciate-retaining total knee arthroplasties.
AB  - The objective of this study was to determine the in vivo medial and lateral
      femorotibial condyle contact positions for 20 subjects having either a posterior
      cruciate-retaining (PCR) or posterior-stabilized (PS) total knee arthroplasty
      (TKA) while sitting and kneeling. The two-dimensional radiographic images were
      converted into three-dimensional images using an iterative computer model-fitting
      technique. Anteroposterior contact positions, axial rotation, and condylar lift
      off were assessed for each subject. In a seated position, the femorotibial
      contact points were, on average, posterior for both TKA groups (PCR: medial = 
      2.4 mm, lateral = -3.4 mm; PS: medial = -5.1 mm, lateral = -8.9 mm; medial,
      P=.21; lateral, P=.08). In a kneeling position, the contact position shifted
      anteriorly for the PCR TKA group (medial = 0.9 mm, lateral = -0.8 mm), whereas
      the contact positions in the PS TKA group remained posterior (medial = -5.6 mm,
      lateral = -8.3 mm; medial, P=.002; lateral, P=.0004). It is hypothesized that
      while in a kneeling position, the posterior cruciate ligament has less resistance
      to the anterior thrust of the femur relative to the tibia than in a PS TKA, in
      which this force is absorbed in the cam-and-post mechanism.

PMID- 11847624
TI  - Evaluation of the Hemocue portable hemoglobinometer after major joint
      arthroplasty.
AB  - We evaluated the potential use of the Hemocue (Hemocue AB, Sweden) portable
      hemoglobinometer on the 1st postoperative evening after major joint arthroplasty.
      We compared hemoglobinometer values with conventional Coulter counter laboratory
      analysis in a population of 67 patients. The hemoglobinometer proved practical,
      economical, and accurate in general, although 2 outlying values were severe
      enough as potentially to influence clinical decision making. Potential causes and
      solutions are discussed.

PMID- 11847625
TI  - Arterial occlusion after total knee arthroplasty: successful management of an
      uncommon complication by percutaneous thrombus aspiration.
AB  - Management of arterial occlusion after total knee arthroplasty is controversial
      in the literature, in part because of the relatively small number of reported
      cases. We report a case of perioperative popliteal artery thrombosis after total
      knee arthroplasty that was treated successfully with percutaneous thrombus
      aspiration and balloon dilation. Immediate intervention prevented ischemic
      muscular necrosis, resulting in full recovery of the limb.

PMID- 11847627
TI  - Mucoraceae infections of antibiotic-loaded cement spacers in the treatment of
      bacterial infections caused by knee arthroplasty.
AB  - Two clinical cases of mycotic infections secondary to knee spacers medicated with
      antibiotics against bacterial infections are presented. Care must be taken
      between the first and second stage (when the spacer is in place), and attention
      must be paid to the management of the surgical wound to avoid secondary
      contamination.

PMID- 11847626
TI  - Psoas abscess associated with infected total hip arthroplasty.
AB  - A 65-year-old man with a left uncemented total hip arthroplasty performed 11
      years previously was admitted with a history of progressive low back pain, left
      hip pain, and sepsis that had begun 6 months earlier. On physical examination, a
      gross, fluctuant mass was palpated in the left thigh. A computed tomography (CT)
      scan revealed a 6.5 x 3 cm left retrofascial psoas abscess communicating with the
      hip joint. The patient underwent irrigation and debridement of the hip with
      removal of the components. The psoas abscess was drained through the iliopsoas
      bursa. A residual psoas abscess was drained percutaneously under CT guidance.
      Cultures isolated Escherichia coli, and the patient responded to 6 months of
      ciprofloxacin therapy. After 1 year, the patient had no evidence of infection.
      Pathways of infection spread, diagnosis, and treatment of a patient with this
      rare association are discussed with a review of the literature.

PMID- 11847628
TI  - Nursing: the discipline and the profession.

PMID- 11847629
TI  - Polarities in nursing science: the plight of the emerging nurse scholar.

PMID- 11847630
TI  - A dialogue on the comparability of research paradigms--and other theoretical
      things.

PMID- 11847631
TI  - Ethical codes and principles: the link to nursing theory.

PMID- 11847632
TI  - A theory of goal attainment: philosophical and ethical implications.

PMID- 11847633
TI  - Constructing curriculum: creating a teaching-learning space.

PMID- 11847634
TI  - Theory-guided, evidence-based reflective practice.

PMID- 11847635
TI  - Human becoming theory: a complement to medical science.

PMID- 11847636
TI  - The state of nursing science: hallmarks of the 20th and 21st centuries.

PMID- 11847637
TI  - A Nightingale-based model for dementia care and its relevance for Korean nursing.
AB  - This article addresses the synchrony between a Western middle-range theory of
      care for persons with dementia and traditional Korean nursing care. The Western
      theory is called a need-driven, dementia-compromised behavior model and is
      heavily influenced by the assessment categories outlined in Nightingale's work.
      This model is presented as congruent with Nightingale's work and then viewed from
      the perspective of traditional Korean nursing. Several congruencies and a few
      incongruencies are found between these Western and Eastern views, and suggestions
      are made for greater consistency between these views.

PMID- 11847638
TI  - Practice with persons living their dying: a human becoming perspective.
AB  - The purpose of this article is to discuss nursing practice with persons who are
      living their dying, from the perspective of Parse's theory of human becoming.
      Quality of life from the person's own perspective is the goal of practice guided
      by Parse's theory; hence, it is particularly relevant for nurses in palliative
      care settings, where quality of life is paramount. The practice methodology is
      explained and illustrated with an example drawn from experiences with a woman in
      a hospice in South Korea. As this woman lived her dying, suffering, joy, and
      sorrow emerged in cocreated relationships with important others.

PMID- 11847639
TI  - Theoretical and empirical description of adult couples' collaborative self-care
      systems.
AB  - Couples' collaborative care systems wherein work of self-care is shared are
      described from the perspective of Orem's nursing theory. Couples (N = 108)
      completed two forms of the Self-As-Carer Inventory: their perception of their own
      and of their partner's self-care agency. Each completed the Couple Form of the
      Family Adaptability and Cohesion Evaluation Scales and self-reports of health at
      this moment and of health in general. The person identified by the couple as
      having more caregiving responsibilities completed the Caregiver Reciprocity
      Scale. Stepwise multiple regression yielded a three-variable model (cohesion,
      dyad gender, and health now), which explained 27% of the variance of
      collaborative care system score. A collaborative care system model is proposed.

PMID- 11847640
TI  - Family nursing interventions: Mexican American early family formation.
AB  - The purpose of this ethnographic study (based on Roy's adaptation model) with 23
      Mexican American families was to assess the similarity of nursing interventions
      that enhance family processes of nurturing, support, and socialization. The
      investigator sought to assess the similarity of nursing interventions to existing
      ways families were nurtured, supported, and socialized and to inquire whether
      young parents would be receptive to nurses intervening in their families. Parents
      rated 20 ways of offering nursing interventions according to dimensions of
      similarity and acceptability and then offered explanatory comments.

PMID- 11847641
TI  - Giving form to the abstract.

PMID- 11847642
TI  - On the use of nursing theory in nurse education, nursing practice, and nursing
      research in Australia.

PMID- 11847643
TI  - A nursing position on global healthcare: our commitment to humankind.

PMID- 11847644
TI  - In different voices.

PMID- 11847645
TI  - Ethical issues from nursing theoretical perspectives.

PMID- 11847646
TI  - An ethical framework for nursing practice: Parse's human becoming theory.

PMID- 11847647
TI  - Emerging discoveries and possibilities in nursing.

PMID- 11847648
TI  - Evidence-based practice: critique and alternative view.

PMID- 11847649
TI  - Women's multiple role stress: testing Neuman's flexible line of defense.
AB  - Women who are both mothers and students are at high risk for experiencing
      multiple role stress. In this exploratory study guided by Neuman's conceptual
      model, the conditions under which role stress develops in these women were
      examined. Specifically, the moderating capabilities of the psychological and
      sociocultural variables in the flexible line of defense, psychological role
      involvement and perceived social support, were investigated. It was found that
      these two variables interacted to explain role stress only in the presence of the
      developmental variable, maternal age. Recommendations concerning conceptual and
      empirical specification of Neuman's model are presented.

PMID- 11847650
TI  - Affirming reflection.

PMID- 11847652
TI  - The effectiveness of therapeutic touch: a meta-analytic review.
AB  - The purpose of this article is to explore the adequacy of published scientific
      evidence supporting therapeutic touch as a nursing intervention. Meta-analytic
      techniques were used to integrate the research-based literature published in the
      past decade. The results seem to indicate that therapeutic touch has a positive,
      medium effect on physiological and psychological variables. It is impossible to
      make any substantive claims at this time because there is limited published
      research and because many of the studies had significant methodological issues
      that could seriously bias the reported results. Resolving these methodological
      issues is imperative for therapeutic touch research to move forward.

PMID- 11847651
TI  - Involvement of relatives in care of the dying in different care cultures:
      development of a theoretical understanding.
AB  - A prerequisite for the staff to be able to guide relatives through the dying
      trajectory is that the staff members know what the relative wants and can do. The
      aim of this study was threefold: (a) to identify and categorize family members'
      involvement in the care of a dying relative, (b) to develop a theoretical
      understanding of their involvement, and (c) to discuss the congruence or
      incongruence between the empirical results and key concepts in Swanson's and
      Watson's theories of caring. The results show that the relatives' involvement
      could be classified into three categories: to know, to be, and to do. Good
      correspondence was found between these three categories and key concepts in
      Swanson's and Watson's theories of caring.

PMID- 11847653
TI  - Energy: its distinctive meanings.

PMID- 11847654
TI  - Adolescent self-esteem: a foundational disposition.
AB  - Based on results of a concept synthesis and concept derivation, an argument is
      made that self-esteem is a human foundational disposition within the self-care
      deficit theory of nursing and, as such, is a component of an individual's self
      care agency. Guided by research literature, the basic conditioning factors of
      age, gender, developmental state, family systems, sociocultural orientation,
      health state, and environmental factors are discussed in regard to their
      influence on the adolescent's developing self-esteem and emerging self-care
      agency.

PMID- 11847655
TI  - Exercise: a unitary concept.
AB  - Nursing science provides the opportunity to frame one's vision of humans and
      health and create interventions that facilitate wellness. This article
      contributes to nursing science by reconceptualizing exercise as a unitary concept
      using Parse's process of concept inventing. Concept inventing is a way to uncover
      the uniqueness of particular concepts and articulate their essence within the
      simultaneity paradigm. It differs from traditional, linear processes that are
      derived from the totality paradigm. Through the process of concept inventing,
      exercise is described within Rogers's science of unitary human beings and
      conceptualized as the purposeful, rhythmic flow of human movement.

PMID- 11847656
TI  - Newman's theory of health applied in family caregiving in Canada.
AB  - This study was conducted using an innovative mode of heuristic inquiry within the
      context of Newman's theory of health as expanding consciousness. Twelve
      caregiving families of persons who were diagnosed with schizophrenia participated
      in the study. In accordance with Newman's theory of health as praxis, the
      majority of the participants in the study recognized their patterns of the whole.
      As a result, they reported understanding and acceptance of their relative's
      mental illness.

PMID- 11847657
TI  - International perspectives. Welcome and introduction.

PMID- 11847658
TI  - A frigid climate.

PMID- 11847659
TI  - Middle-range theories: do they foster the development of nursing science?

PMID- 11847660
TI  - Prostatitis: an advanced nursing practice guideline.

PMID- 11847661
TI  - Integrity in the advancement of nursing knowledge.

PMID- 11847662
TI  - Distance learning: issues emerging as the paradigm shifts.

PMID- 11847663
TI  - The Internet: extending our capacity for scholarly inquiry in nursing.

PMID- 11847664
TI  - The ethics of Orem's theory.

PMID- 11847665
TI  - Health policy and regulatory decisioning based on nursing theory.

PMID- 11847666
TI  - Where does the information superhighway go?

PMID- 11847667
TI  - The state of nursing science: reconceptualizing for the 21st century.

PMID- 11847668
TI  - The teaching-learning process and the theory of human becoming.
AB  - The purpose of this article is to contribute to the human becoming school of
      thought in nursing by defining the teaching-learning process. From a human
      becoming perspective, teaching-learning is a process of engaging with others in
      coming to know. The teaching-learning process as a lived experience of engaging
      with others in coming to know involves the multidimensional processes of
      expanding imaginal margins, naming the new, going with content-process shifts,
      abiding with paradox, giving meaning, inviting dialogue, noticing the now, and
      growing story.

PMID- 11847669
TI  - Living with serious mental illness: the desire for normalcy.
AB  - This article describes the desire for normalcy as experienced by 6 men and 13
      women with serious mental illness based on secondary analysis of data from two
      previous qualitative studies. Original data were collected by structured and semi
      structured interviews, and thematic analysis was done. Major categories of desire
      for normalcy are having normal things and experiences; doing meaningful
      activities; and being well, safe, free, and independent. Self-care actions to
      promote and maintain normalcy are identified, and finding are discussed in
      relation to Orem's self-care deficit theory of nursing. Implications for nursing
      theory, research, and practice are addressed.

PMID- 11847670
TI  - Parenting processes: a descriptive exploratory study using Peplau's theory.
AB  - A descriptive exploratory study using Peplau's theory was conducted to
      investigate the experiences of parenting among those who have been identified as
      having positive parenting processes. Using guide questions developed from the
      objectives of the study, the researcher interviewed 16 parents who had at least
      one child who had completed high school. Transcribed interviews were examined for
      themes following the analysis-synthesis procedure. The findings illustrated
      parents' beliefs that their children's contentment, connectedness, and
      independence were indications of positive outcomes and that parents'
      communication of expectations, active strategies, and responses to challenges
      were critical in facilitating their children's growth. Recommendations for
      practice, research, and education are suggested.

PMID- 11847671
TI  - Measuring dreaming as a beyond waking experience in Rogers's conceptual model.
AB  - This article describes the development of an instrument, the Assessment of Dream
      Experience. This instrument was developed within the context of Rogers's
      conceptual model, the science of unitary human beings, and was designed to
      measure dreaming as a beyond waking experience. A detailed description of the
      instrument and its psychometric properties is presented. Recommendations for
      future use are provided.

PMID- 11847672
TI  - Urine control theory derived from Roy's conceptual framework.
AB  - The urine control theory, a middle range theory substructed from Roy's adaptation
      model, is presented to explicate the phenomenon of urine control. Urine in the
      bladder is identified as the focal stimulus, and the impact of the cognator
      subsystem in relation to urine control is described. The role of contextual
      stimuli related to mobility and the environment is also described. Relationships
      between concepts are explained and supported with individual case studies. The
      case findings are used to exemplify the interrelationships in the model. The
      urine control theory can be used by practitioners to inform practice and by
      researchers to guide research designs.

PMID- 11847673
TI  - The aesthetics of caring: where folk healers and nurse theorists converge.

PMID- 11847674
TI  - The meaning of new age: the judging and misjudging of values and beliefs.

PMID- 11847675
TI  - Art as a path of inquiry.

PMID- 11847677
TI  - Community: an alternative view.

PMID- 11847676
TI  - Rogerian ethics: an ethical inquiry into Rogers's life and science.

PMID- 11847678
TI  - Community practice guided by a nursing model.

PMID- 11847679
TI  - A unitary-transformative nursing science: potentials for transcending
      dichotomies.

PMID- 11847680
TI  - Mexican American family processes: nurturing, support, and socialization.
AB  - The purpose of this ethnographic study with Mexican American families was to
      document characteristics of Mexican American family processes of nurturing,
      support, and socialization. Audiotaped conversations with participants were
      transcribed verbatim in Spanish or English. Content analysis was used to derive
      characteristics of family processes. Family nurturing was characterized by being
      kin-based and intimate in nature. Family support was kin-based, with material
      support oriented toward household needs; with emotional support grounded in
      shared stories, problem solving, and prayer; and with informational support
      offered in consejos (wisdom sayings and words of advice), stories, and guidance.
      Family socialization was kin-based, hierarchical, and ritualistic.

PMID- 11847681
TI  - The lived experience of serenity: using Parse's research method.
AB  - Parse's research method was used to investigate the meaning of serenity for
      survivors of a life-threatening illness or traumatic event. Ten survivors of
      cancer told their stories of the meaning of serenity as they had lived it in
      their lives. Descriptions were aided by photographs chosen by each participant to
      represent the meaning of serenity for them. The structure of serenity was
      generated through the extraction-synthesis process. Four main concepts--steering
      yielding with the flow, savoring remembered visions of engaging surroundings,
      abiding with aloneness-togetherness, and attesting to a loving presence--emerged
      and led to a theoretical structure of serenity from the human becoming
      perspective. Findings confirm serenity as a multidimensional process.

PMID- 11847682
TI  - The construct of thriving in pregnancy and postpartum.
AB  - This article explores the construct of thriving as an integration of nutritional
      (manifested in weight), psychosocial, and lifestyle concerns of childbearing
      within the context of Orem's self-care deficit theory. Provisional definitions of
      thriving in pregnancy and postpartum are proposed. Preliminary dimensions of
      thriving in postpartum are based on factor analysis of weight, lifestyle, and
      psychosocial data from 145 women after childbirth. Four dimensions emerged:
      psychosocial distress, lifestyle patterns, a weight factor, and a body image
      factor. Although the dimensionality of postpartal thriving reported is
      preliminary, it provides a beginning foundation for assessment and intervention
      for postpartal women.

PMID- 11847683
TI  - The philosophical core of King's conceptual system.
AB  - Aristotelian understanding of being human is presented as the philosophical core
      of King's conceptual system. A summary of King's thought is organized according
      to contemporary influences. The article then turns to what Aristotle teaches
      about the composition of the world and what it means to be a human being.
      Wallace's life-powers model of the soul brings these insights into contemporary
      thought. Aristotelian philosophy completes King's account of the personal system
      by providing insight into what it is to be human. Parallels in the reasoning of
      transaction and Aristotelian deliberation are further evidence of classical
      influences within King's work.

PMID- 11847684
TI  - Caring needs of patients with rheumatoid arthritis.
AB  - The goal of this study was to identify, through the application of Watson's 10
      carative factors, the caring needs specific to the human experience of having
      rheumatoid arthritis and undergoing acupuncture treatment. The study was
      conducted at a large university hospital in Stockholm, Sweden. Interviews were
      conducted during manual acupuncture treatment employing a conversation guide
      derived from Watson's theory of caring. Six women had 20 sessions each over an 11
      week period. A thematic analysis of the resulting 120 audiotaped sessions
      revealed four predominant themes: seeking help, searching for meaning,
      uncertainty, and fear of being disappointed. These four phenomena captured the
      complexities of the physical, emotional, social, and existential experiences of
      the patients.

PMID- 11847685
TI  - Through a visitor's lens.

PMID- 11847686
TI  - Learning to be still.

PMID- 11847687
TI  - Authorship: whose responsibility?

PMID- 11847689
TI  - Coming to terms with perceived danger. A researcher's narrative.
AB  - Little attention has been given to the topic of perceived or imagined dangers in
      fieldwork, even though such dangers may significantly affect both collection and
      interpretation of data in qualitative research. Furthermore, methodological
      arguments persist in regard to interpreting qualitative research that gives voice
      simultaneously to the research participant and the researcher. In this article
      reflexivity and narrative methods were used to examine the concept of perceived
      danger(s) in a field setting using naturalistic inquiry. First, reflexivity and
      narrative methods were used to retrospectively construct a personal narrative
      that describes the impact of the field experience on the researcher. Then,
      narrative analysis was used to interpret this personal narrative and to further
      examine why the researcher "perceived" certain dangers, and how she came to know
      that these risks and dangers were presumed but unwarranted. This narrative is an
      example of how qualitative researchers can give voice to their field experiences.

PMID- 11847688
TI  - Alcoholics Anonymous and nursing. Lessons in holism and spiritual care.
AB  - Alcoholic Anonymous (AA) is a worldwide, million-member organization that has
      assisted countless alcoholics to achieve sobriety through a spiritual program of
      recovery from alcoholism. Based on spiritual principles known as the "Twelve
      Steps" and "Twelve Traditions," AA has provided a model for other recovery
      programs such as Narcotics Anonymous (NA), Gamblers Anonymous (GA), and Sex and
      Love Addicts Anonymous (SLAA). Recovery in AA appears to involve a process of
      self-transcendence. In recent years, nursing scholars have increasingly explored
      the concepts of self-transcendence and spirituality as they apply to nursing
      theory and practice. This article explores the roots and spiritual dimensions of
      12-step recovery programs. It further explores the ways in which theoretical and
      clinical knowledge about the delivery of spiritual care interventions may be
      gained from an understanding of AA's spiritual approach to recovery.

PMID- 11847690
TI  - Lifelong learning in the new millennium.

PMID- 11847691
TI  - Empirical evidence for the nature of holistic comfort.
AB  - The nursing outcome of holistic comfort encompasses physical, psychospiritual,
      social, and environmental aspects of human nature. The primary purpose of this
      study was to test four propositions about the nature of comfort: (a) Comfort has
      equal proportions of state and trait characteristics; (b) comfort is sensitive to
      changes over time; (c) when subjects are exposed to an effective intervention,
      they demonstrate differences in comfort that increase in a linear way compared to
      a control group; and (d) the whole (total comfort) is greater than the sum of its
      parts (relief plus ease plus transcendence). A secondary purpose of this study
      was to present preliminary concurrent validity between two types of comfort
      instruments, a traditional questionnaire with a Likert-type format and visual
      analog scales. Findings were positive for all theoretical propositions and
      moderate concurrent validity between the Radiation Therapy Comfort Questionnaire
      and the visual analog scale for total comfort was demonstrated.

PMID- 11847692
TI  - Cardiac therapy for men with coronary artery disease. The lived experience.
AB  - A phenomenological inquiry was conducted to uncover the lived experience of
      cardiac therapy for men with coronary artery disease in Northwest Ohio. Five men
      age 60 to 70 years were purposively selected to participate. Data obtained from
      individual audiotaped interviews were analyzed using Colaizzi's method. Eight
      major themes emerged: (a) feelings of fear and disbelief, (b) being aware of
      mortality, (c) losing control of self, (d) halting usual activities and future
      plans, (e) heightening awareness of spirituality and belief in a higher power,
      (f) resigning to accept external forces and required changes, (g) increasing
      sense of well-being, and (h) receiving a second chance and moving forward. This
      study makes valuable contributions to nursing by increasing awareness of actual
      lived experiences of cardiac therapy for men, offering direction for cardiac
      therapy programs to assist men with holistic lifestyle modifications that enable
      them to increase wellness, and serving as an impetus for further research.

PMID- 11847693
TI  - Orem's self-care deficit nursing theory: its philosophic foundation and the state
      of the science.
AB  - There is a preponderance of descriptive studies, ranging from those using a
      simple descriptive correlational approach to multivariate approaches. Only one
      study is clearly identified as an experimental study (Moore, 1987) and two
      clearly identified as replication studies (Lenatsch, 1999; Schott-Baer, Fisher, &
      Gregory, 1995). Fewer than half make clear links between the variables being
      examined and situations of nursing practice; that is, they examine elements of
      the theory of self-care without making the link to nursing practice an explicit
      part of the study. While this work is increasing our knowledge about self-care
      (Stage II), further work needs to be done to put the results of these in the
      context of nursing practice as in Stages III, IV, or V. Most of the studies
      reviewed are Stage II and provide an enhanced or broader description of an
      element or component of the theory, empirically describing the relationships
      between or among age, gender, self-care actions, disease, and so forth. These
      studies add to our understanding of existing and known or proposed relationships
      within the extant theory. The majority of studies examine self-care and/or self
      care deficits. There are many studies but little evidence that sustained research
      programs are developing and expanding the theory. The bricks are piling up around
      the framework, but only a few scholars are working on building the walls. These
      programs of research are occurring in universities where a critical mass of
      interested scholars and students can be found. The use of theoretical language is
      sometimes imprecise and at other times inaccurate. Valid new terms are introduced
      but the relationship to existing theoretical constructs is not always explicit.
      There is little critical review of research in the literature. Ongoing dialog
      among scholars is minimal. There is a need for nurse scholars to come together
      and to engage in such a dialogue to enhance the work. Given the relatively short
      history of nursing research and, more importantly, the conduct of nursing theory
      based research, the number and quality of the work being conducted is quite
      remarkable. There has been a substantial amount of work produced and the quality
      of it has improved over time. Orem has provided nurse researchers with a
      theoretical system comprising an ontological structure, related epistemology, and
      numerous models that give direction to scholarly efforts. Scholars using this
      theoretical system would be well-advised to use these in conceptualizing and
      interpreting their work.

PMID- 11847694
TI  - Beneficence: honoring the commitment.

PMID- 11847695
TI  - The nurse scholar of the 21st century.

PMID- 11847696
TI  - The test of a nursing theory: a personal view.

PMID- 11847697
TI  - Nursing reformation: historical reflections and philosophic foundations.

PMID- 11847698
TI  - Measurement of Orem's basic conditioning factors: a review of published research.
AB  - The purpose of this review was to examine published research on basic
      conditioning factors described in Orem's self-care deficit theory of nursing, in
      order to identify operational definitions, measurement strategies, and the
      results of the analyses. Thirty-five research articles published between 1987 and
      1997 met the criteria for inclusion in the review. Consensus or lack of consensus
      in operational definitions for specific factors was determined and successful
      measurement methods were identified. Recommendations are made for revising
      conceptual and operational definitions. Suggested measurement strategies for the
      factors are discussed.

PMID- 11847699
TI  - Concept inventing: a process for creating a unitary definition of having courage.
AB  - Having courage is all-at-once inherent in being human and immeasurable. It is
      intertwined with what living is all about. This article discusses existing
      theoretical views of courage, provides examples of the importance of the
      phenomenon for health and quality of life, and presents a unique definition of
      having courage that emerged through the process of concept inventing--a
      multidimensional process of creating unitary concepts. The definition having
      courage is deliberate steadfast risking while creatively living the cherished
      with opportunities-restrictions is explored in relation to the human becoming
      theory, and suggestions for future research are made.

PMID- 11847700
TI  - Pattern of expanding consciousness in midlife women: creative movement and the
      narrative as modes of expression.
AB  - This study is based on Newman's theory of expanding consciousness; it expands
      Newman's method to include creative movement as a mode of expression. The
      researcher engaged in two in-depth interviews and one creative movement group
      experience with each of 17 midlife women. Results demonstrate expanding
      consciousness at midlife, with patterns of meaning identified in relationships
      with others, self, and spirit as well as challenges of loss, illness, and threats
      to relationships. Activities of consciousness were choosing, balancing,
      accepting, and letting go. Concepts of flow, turbulence, and a movement dialectic
      were identified in study findings. Creative movement supported self-awareness.

PMID- 11847701
TI  - Cognitive adaptation and self-consistency in hearing-impaired older persons:
      testing Roy's adaptation model.
AB  - This study, based on constructs from Roy's adaptation model, examined the
      relationship between cognitive adaptation processes and self-consistency in
      hearing-impaired elders (N = 130). Data were collected through survey
      questionnaires. Major research hypotheses were formulated and tested. Results of
      this study supported Roy's theoretical proposition of cognitive adaptation
      processes and their role in the maintenance of self-consistency. Three cognitive
      processes (clear focus and methods, knowing awareness, and self-perception)
      significantly contributed to the maintenance of self-consistency. Understanding
      these cognitive processes helps nurses to promote effective adaptation in older
      persons.

PMID- 11847703
TI  - Obfuscating: the persistent practice of misnaming.

PMID- 11847702
TI  - The South Dakota Board of Nursing theory-based regulatory decisioning model.

PMID- 11847704
TI  - Paradigm shift or paradigm drift? A meditation on commitment and transcendence.

PMID- 11847705
TI  - The microintroducer technique for peripherally inserted central catheter
      placement.
AB  - The microintroducer approach to obtaining initial venous access and threading a
      peripherally inserted central catheter (PICC) with and without imaging support is
      described. Equipment needed and steps to complete the procedure are described.
      Initial patient assessment and problem solving are discussed, as is application
      of the microintroducer technique in clinical practice. Potential complications
      and challenges are included.

PMID- 11847706
TI  - The Joint Commission's "improving organizational performance" standards for home
      infusion therapy providers.
AB  - In today's homecare environment, optimizing operational efficiency and making
      data-driven decisions is essential. Home infusion therapy organizations that are
      accredited by the Joint Commission on Accreditation of Healthcare Organizations
      (Joint Commission) will find a heavy emphasis on the standards for improving
      organizational performance during the homecare survey process. The standards from
      the "Improving Organizational Performance" chapter are reviewed, and the Joint
      Commission's requirements for meeting the intent of the standards are discussed.

PMID- 11847707
TI  - Cytotoxic chemotherapy in the treatment of nonmalignant disease.
AB  - The term chemotherapy refers to an ever-increasing number of drugs that work with
      varying specificity against the malignant cells of tumors. These drugs work in
      several different ways, including direct and indirect cytotoxicity and
      immunosuppression. This diversity of mechanisms of action has led to the use of
      cancer chemotherapeutic agents in the treatment of several nonmalignant diseases.
      The use of cytotoxic drugs in nonmalignant disease is reviewed, and
      recommendations are provided for safe handling, administration, and the
      management of expected toxicities.

PMID- 11847708
TI  - Peripherally inserted central catheters in the patient with cardiomyopathy. The
      most cost-effective venous acess.
AB  - While waiting for a heart transplant, patients with cardiomyopathy receive
      positive inotropic agents and other medications that require ongoing venous
      access. To evaluate the cost effectiveness of bedside peripherally inserted
      central catheter (PICC) placement, a retrospective analysis was conducted
      comparing four types of venous access. Almost 4000 dwell days support the premise
      that bedside PICC placement is the most cost-effective method of providing
      ongoing venous access to the patient with cardiomyopathy.

PMID- 11847709
TI  - Professional ethics. A case study of infusion nurse consultants.
AB  - As the healthcare system continues to reform, opportunities exist for infusion
      nurses to expand their practice into the business world. Traditionally,
      biomedical ethics have been used in nursing education as a framework for
      identifying and responding to ethical dilemmas. However, in the business world,
      professional ethics may be more subtle and insidious. A case study of ten
      infusion nurse consultants and their experiences with professional ethical issues
      is presented. Data were obtained using interviews, and content analysis revealed
      emergent themes of integrity and intuitive knowing with related categories.

PMID- 11847710
TI  - Forgiveness. A concept analysis.
AB  - This article provides an operational definition of forgiveness as a first step in
      the systematic analysis of the concept. Using the method described by Walker and
      Avant (1995), the authors identify the attributes and characteristics of
      forgiveness and its theoretical and practical implications for nursing. Sample
      cases from clinical practice help illustrate the concept further. Further nursing
      research needs to test the theoretical relationships between forgiveness and
      nursing practice outcomes.

PMID- 11847711
TI  - Why don't consumers seek our advice?

PMID- 11847712
TI  - Strengthening transcendent meaning. A model for the spiritual nursing care of
      patients experiencing suffering.
AB  - The purpose of this article is to present a model for the spiritual nursing care
      of patients experiencing suffering. Meaningless suffering can lead to spiritual
      disintegration. However, the finding of transcendent meaning in the suffering
      experience can be a profound attenuator of how the suffering is experienced. This
      model outlines five categories for a comprehensive spiritual assessment: (a)
      authority and guidance, (b) experience and emotions, (c) community, (d) rituals
      and practices, and (e) vocation and consequences. For each of the five
      categories, interventions are identified that could strengthen transcendent
      meaning in the suffering.

PMID- 11847713
TI  - Healing presence.
AB  - Since the introduction of presence as a concept in nursing literature in the
      early 1960s, nurse philosophers, theorists, and researchers have attempted to
      define and describe presence as it relates to nursing practice. Understanding of
      nursing presence and its link, if any, to nurse-patient interaction is basically
      subjective and intuitive. This article is based on the assumption that nursing
      presence fully understood may result in greater patient satisfaction and healing
      potential. A three-stage, hierarchical model culminating in healing presence is
      used to understand the nurse-patient dyad. The model is calibrated in terms of
      nursing maturity using Benner's novice nurse/expert nurse idea, Hanneman's expert
      nurse/nonexpert nurse view, Zaner's vivid-presence/copresence, and Doona, Chase,
      and Haggerty's nursing presence.

PMID- 11847714
TI  - The effects of shiatsu on lower back pain.
AB  - Shiatsu, a specific type of massage, was used as an intervention in this study of
      66 individuals complaining of lower back pain. Each individual was measured on
      state/trait anxiety and pain level before and after four shiatsu treatments. Each
      subject was then called 2 days following each treatment and asked to quantify the
      level of pain. Both pain and anxiety decreased significantly over time.
      Extraneous variables such as gender, age, gender of therapist, length of history
      with lower back pain, and medications taken for lower back pain did not alter the
      significant results. These subjects would recommend shiatsu massage for others
      suffering from lower back pain and indicated the treatments decreased the major
      inconveniences they experienced with their lower back pain.

PMID- 11847715
TI  - Spirituality of healing touch participants.
AB  - Nurses and nonnurses involved in Healing Touch training were studied to determine
      if there was a difference in their perception of spirituality. There was no
      difference between the nurses and nonnurses on either the Spiritual Perspective
      Scale (F = .001, p = .970) or the Questionnaire on Spiritual and Religious
      Attitudes (F = .024, p = .878). There was a significant difference between the
      six levels of training in Healing Touch classes completed by the participants on
      the Spiritual Perspective Scale (F = 7.079, p = .000). The upper-level classes
      had higher scores than the lower levels. There was a difference on the
      Questionnaire on Spiritual and Religious Attitudes between levels of instruction
      completed (F = 3.326, p = .003). This suggests that there is a heightened sense
      of spiritual awareness in those in the higher levels of the program. It may be
      that involvement in an energy-based therapy is one way to develop spiritual
      awareness.

PMID- 11847717
TI  - Identification of pancreatitis in the ambulatory setting.
AB  - Acute pancreatitis can be life threatening. As a nurse practitioner, you are
      expected to accurately diagnose, treat, and refer as necessary. Because many
      different types of disease can cause abdominal pain, it is prudent to know signs,
      symptoms, and risk factors for pancreatitis. After reviewing this article, nurses
      should have a better understanding of acute pancreatitis and be able to recognize
      when it strikes.

PMID- 11847716
TI  - Screening for colorectal cancer: developing a preventive healthcare program
      utilizing nurse endoscopists.
AB  - Colorectal cancer is the second leading cause of cancer-related deaths in the
      United States. In 2000, approximately 130,200 new cases of colorectal cancer will
      be diagnosed, and 56,300 persons will die from the disease (Greenlee, Murray,
      Boldan, & Wingo, 2000). A survey conducted for the National Colorectal Cancer
      Roundtable by the Gallup Organization, found that 47% of people over 50 are not
      being screened. The National Colorectal Cancer Awareness Month, which began in
      March 2000, will educate Americans age 50 and older and prescribe physicians
      about the importance of colorectal cancer screening tests. The effect of
      increased education and directing physicians to include colorectal screening for
      their patients will create a need for non-physician endoscopists to meet the
      screening needs of the population. A colorectal cancer screening center was
      developed at a large Midwestern teaching hospital utilizing nurse endoscopists.
      The purpose of this article is to provide information for institutions to develop
      and implement a colorectal cancer screening center utilizing nurse endoscopists.

PMID- 11847718
TI  - A review of the causes of upper gastrointestinal tract bleeding in children.
AB  - Bleeding may occur anywhere along the gastrointestinal tract, which covers a
      large surface area and is highly vascularized. While gastrointestinal bleeding is
      an alarming symptom for patients of any age, it can cause panic for children and
      their care givers. Early diagnosis and treatment of gastrointestinal bleeding may
      be essential. The differential diagnosis of bleeding from the upper
      gastrointestinal tract in infants and children includes numerous possibilities
      ranging from benign disorders which require little or no treatment at all, to
      serious diseases which require immediate intervention. This article reviews a
      variety of disorders which may cause upper gastrointestinal bleeding in infants
      and children. This is part one, of a two part series, on gastrointestinal
      bleeding in children. Part two will discuss bleeding from the lower
      gastrointestinal tract.

PMID- 11847719
TI  - Ethical decisions regarding nutrition and the terminally ill.
AB  - Care of the terminally ill is rewarding and challenging. Nurses have the
      potential to affect the quality of these patients' lives. A recurrent theme
      voiced by terminally ill patients and their families is the nutritional
      ramifications associated with the cessation of nutritional intake. Various
      ethical perspectives provide a useful guide for decision making when determining
      whether fluids and nutrition should be continued in the terminally ill. This
      article will discuss various ethical perspectives in relation to nutrition
      cessation in the terminally ill. Basic physiologic changes that occur in the
      terminal patient will also be addressed. Nurses play an important role in
      insuring quality of care, particularly in supporting patients and families as
      they make decisions regarding nutritional management at the end of life.

PMID- 11847720
TI  - Educational care path for the endoscopic patient.
AB  - Complex healthcare systems make it increasingly difficult for healthcare
      providers to coordinate patient care throughout the healthcare continuum. In
      order for patients to actively participate in their care, we need to develop
      tools that include them in this process. Our Short Stay (endoscopy) staff
      observed that pre-procedure patient teaching materials from area physician
      offices did not reflect consistent information. After meeting with several
      physicians and their office staff, our unit decided to use a Care Path tool
      designed for healthcare providers and adapt relevant areas for patients' use.
      Keeping in mind that patient satisfaction is an important focus for healthcare
      facilities, we successfully redesigned our unit's informational pamphlet into an
      educational tool resembling a Care Path to be used by our patients in their
      preparation and education for an endoscopic procedure.

PMID- 11847721
TI  - Complementary healthcare practices.
AB  - This column provides a brief overview of the historical use of herbs for
      hepatobiliary disease. It includes information regarding both the harmful and
      helpful effects of herbs on the hepatobiliary system. Certainly more research is
      needed. Studies are currently in progress, many funded by grants from various
      agencies including the National Institute of Health. Since one-third of patients
      attending liver clinics are using these potentially helpful or harmful herbs, it
      is an important issue for gastroenterology nurses, associates, and other health
      care providers to address. We must increase our knowledge, advocate for safety
      and research, and discuss the use of herbs in a non-judgmental, informed manner.

PMID- 11847722
TI  - Virtual colonoscopy: a new approach for colorectal cancer screening.
AB  - Virtual endoscopy is the processing of computerized tomography image data to
      create a virtual environment of the human body to allow diagnosis of disease
      processes. This new technique allows the observer the opportunity to interact
      with an image that is artificially generated by the computer. Virtual colonoscopy
      provides a method for processing data that can display computer images of the
      colon in a more anatomic life-like format to facilitate image interpretation and
      improve diagnostic accuracy. The clinical application of virtual endoscopic
      techniques is also being used with other procedures such as bronchoscopy,
      gastroscopy, cystoscopy, sinus imaging, virtual angioscopy, and cerebral
      ventriculography. Current screening recommendations for colorectal cancer are
      discussed in this article along with methods, advantages, challenges, and future
      opportunities for virtual colonoscopy.

PMID- 11847723
TI  - Where have all the nurses gone?

PMID- 11847724
TI  - What are you doing to impact the nursing shortage?

PMID- 11847725
TI  - Nursing endoscopic training: the next step.

PMID- 11847726
TI  - Because you're someone they listen to, push prevention through education about
      screening.

PMID- 11847728
TI  - Balloon-type versus non-balloon-type replacement percutaneous endoscopic
      gastrostomy: which is better?
AB  - Percutaneous endoscopic gastrostomy (PEG) has been an established procedure for
      nearly 20 years. Caring for patients with a PEG has been incorporated into the
      practice of nurses in most gastroenterology settings. Several practice-related
      questions have arisen, particularly in relation to replacement PEGs. In an
      attempt to obtain relevant information for decisions relating to cost
      effectiveness and providing optimum care for PEG replacement, two clinical
      research questions were studied: (1) is there a difference in patient (stomal)
      response related to two different replacement PEG tubes, and (2) is there a
      difference in the duration (life-span) between the two types of replacement
      tubes? A non-experimental, two-group descriptive study was conducted to answer
      the two clinical research questions. Two types of replacement PEG tubes were
      evaluated: a balloon type and a non-balloon type. Stoma response (recording skin
      and insertion site characteristics) and PEG life span were the measures of
      interest. Differences in the occurrence of skin and insertion site problems
      between the two groups were not statistically significant. Differences between
      the life spans of the two tubes were found to be statistically significant at
      three time intervals. Findings give information to the practitioner involved in
      making independent and interdependent practice decisions when planning care for
      patients with a PEG. Suggestions for additional research and replication are
      included.

PMID- 11847727
TI  - Educating patients after conscious sedation for gastrointestinal procedures.
AB  - Medication for conscious sedation during gastrointestinal (GI) diagnostic
      procedures causes amnesia, thereby preventing patients from recalling
      postprocedure instructions or follow-up appointments. A serious complication
      after GI diagnostic procedures is bleeding, which can occur if patients take
      aspirin or nonsteroidal anti-inflammatory agents after the procedure. Past
      research revealed that 73% of patients did not remember instructions. The purpose
      of this randomized controlled trial was: (1) to determine if patients with wrist
      bands remember to read their postprocedure instructions, and (2) to determine
      what patient demographics are associated with failure to read postprocedure
      instructions. Sixty-one GI clinic outpatients participated in this Veterans
      Affairs Medical Center study, received routine written instructions before and
      after GI diagnostic procedures, and were randomly assigned to one of two groups:
      control group (standard care plus next-day phone call) or intervention group
      (wrist band plus standard care plus next-day phone call). A memory test evaluated
      patients' knowledge of procedure results, date of follow-up appointment, and
      medications. Results indicated no significant differences in the memory test
      between the groups (t = 0.9, p = .36). Patients 65 years of age and older had
      scores indicating memory problems, regardless of the wrist band (r = 0.19, p =
      .06). The wrist band was ineffective as a reminder to read instructions; rather,
      the next-day phone call served as the reminder.

PMID- 11847729
TI  - Biopsy forceps: disposable or reusable?
AB  - Current debate surrounds the cost-effectiveness of disposable and reusable biopsy
      forceps. Although a complex and arduous task, performing a cost analysis may be
      necessary to determine which forcep type is more cost-effective. Costs associated
      with disposable biopsy forceps include their initial cost as well as storage and
      disposal costs. In addition to initial cost, costs associated with reusable
      biopsy forceps include reprocessing, maintenance, and repair costs. Estimating
      the number of times forceps are likely to be reused is also essential to
      evaluating the cost-effectiveness of reusable biopsy forceps. In general, once a
      reusable biopsy forcep performs a threshold number of procedures, it becomes more
      cost-effective than a disposable forcep. While reusable biopsy forceps may be
      more suitable and cost-effective for larger gastrointestinal endoscopy centers
      that perform many procedures per day, the convenience of disposable biopsy
      forceps may make them the more appropriate choice for centers that are smaller
      and perform only a few procedures each day. Due to significant decreases in the
      initial cost of disposable biopsy forceps, the cost-effectiveness of reusable
      biopsy forceps is waning. This article reviews the various issues associated with
      disposable versus reusable biopsy forceps and provides readers with guidelines
      for evaluating the appropriateness of both forcep designs in their unique
      practice setting.

PMID- 11847730
TI  - Manual cleaning of endoscopes: a comparison study of syringe versus suction
      methods using the endo-suction cleaning system.
AB  - The manual syringe method of cleaning endoscopes involves numerous problems,
      including cross-infection, contamination, wasted time, and employee safety
      issues. This article describes the development of an alternative system by a
      nurse entrepreneur for endoscopic cleaning using a suction method. Scientific
      findings gathered over four years are presented supporting the efficacy and
      usefulness of this system, the Endo-Suction Cleaning System, also known as the
      PSK System.

PMID- 11847731
TI  - An interview with nurse entrepreneur Barbara Puszko.

PMID- 11847733
TI  - Pancreatic enzyme therapy and nutritional status of outpatients with chronic
      pancreatitis.
AB  - Patients with chronic pancreatitis are at risk for poor nutritional status. The
      two major clinical features of chronic pancreatitis are abdominal pain and
      maldigestion, both resulting in malnutrition. Abdominal pain often results in
      decreased oral intake, and decreased enzyme production results in maldigestion.
      Enzyme therapy often is included in treating chronic pancreatitis. There is
      limited data on the nutritional assessment of outpatients with chronic
      pancreatitis, and the efficacy of the use of enzyme therapy remains
      controversial. Serum albumin level and measurement of ideal body weight are two
      simple measures of nutritional status that can be obtained by gastroenterology
      nurses. A retrospective chart review was done of patients seen in our outpatient
      clinic for management of chronic pancreatitis. Serum albumin levels, an indicator
      of protein calorie malnutrition, were reviewed for 34 patients. Thirty-three
      percent of these patients were found to have mild-to-moderate protein calorie
      malnutrition as evidenced by low serum albumin levels. Enzyme therapy information
      was reviewed for 33 patients. Patients receiving enzyme therapy had better
      nutritional status based on both serum albumin levels and percent of ideal body
      weight. Gastroenterology nurses can be instrumental in the recognition and
      treatment of nutritional deficiencies in chronic pancreatitis.

PMID- 11847732
TI  - A review of the causes of lower gastrointestinal tract bleeding in children.
AB  - Bleeding may occur anywhere along the gastrointestinal (GI) tract, which covers a
      large surface area and is highly vascularized. Seeing blood in the child's
      stools, the caregiver and child may become extremely anxious, fearing a
      devastating diagnosis. The differential diagnosis of lower GI bleeding in infants
      and children, however, includes numerous possibilities ranging from benign
      disorders, which require little or no treatment at all, to serious diseases that
      require immediate intervention. This article reviews a variety of disorders that
      may produce lower GI bleeding in infants and children. This is Part 2 of a two
      part series on GI bleeding in children. Part 1 discussed bleeding from the upper
      GI tract.

PMID- 11847734
TI  - Guidelines for preventing sensitivity and allergic reactions to natural rubber
      latex in the workplace.

PMID- 11847735
TI  - Milk thistle and the treatment of hepatitis.
AB  - Gastroenterology nurses and associates will find it helpful to be informed about
      milk thistle (silybum marianum), a popular, safe and promising herb used by
      patients with liver disease. Silymarin is a derivative from the milk thistle
      plant with few side effects that has been safely used for centuries to treat
      liver ailments. Since the 1970s, there has been a reemergence of the marketing
      and use of silymarin. Research results of some small studies suggest silymarin
      has hepatoprotective, antiinflammatory, and regenerative properties producing a
      beneficial effect for some types of hepatitis. It is unclear, however, whether
      silymarin might interfere with the effect of interferon or ribavirin. A well
      designed, placebo-controlled study of a larger population is needed. It is
      certainly encouraging that a large collaborative study is currently underway for
      milk thistle therapy in hepatitis C. This study is funded by NCCAM, the National
      Institute of Allergy and Infectious Diseases (NIAID), and the National Institute
      of Diabetes and Digestive and Kidney Diseases (NIDDK). Research updates are
      available online at www.nccam.nih.gov and through the NCCAM Clearinghouse at 1
      888-644-6226.

PMID- 11847736
TI  - 2000 Mosby Geriatric Nurse Manager Award recipients: Karen A. Thompson and Sharon
      Stahl Wexler.

PMID- 11847738
TI  - A simple case of anemia: pathophysiology of a common symptom.
AB  - Anemia is a common symptom associated with a variety of diseases, disorders, and
      dietary deficiencies. A review of hemoglobin and hematocrit levels may not be
      sufficient to determine the severity of the underlying problem. This article
      gives the reader an enhanced understanding of red cell morphology and reviews
      some of the common problems associated with anemia.

PMID- 11847739
TI  - Focus on factors.
AB  - Recombinant factor VIII concentrates used in the treatment of hemophilia A have
      provided freedom from human viral contamination for hemophiliacs who rely on
      frequent infusions to control bleeding. This article provides a historical
      perspective on the treatment of the various hemophilia types and current
      treatment methods for these and other inherited coagulopathies. Therapy
      complications associated with replacement factors and patient management issues
      will be addressed.

PMID- 11847740
TI  - Blood sample collection from a peripheral catheter system compared with
      phlebotomy.
AB  - Hospital experiences often are punctuated with pain related to common procedures,
      such as venipuncture. An alternative to venipuncture involves obtaining samples
      from an existing peripheral vascular saline lock device. To validate such a
      collection, this study compared the accuracy of serum chemistry tests performed
      on samples taken concurrently from the saline locks and by phlebotomy. No
      clinical differences were noted within the 17 sets of ion assays, and both
      potassium and chloride determinations demonstrated no significant statistical
      differences between the sample groups. Documented rates of sample hemolysis (21%)
      and difficulties experienced in collection suggest that blood sampling from an
      existing peripheral saline lock device is best suited to inpatients undergoing
      multiple blood sampling necessitated by short-term investigative procedures or
      crisis management.

PMID- 11847741
TI  - Hematopoiesis, stem cells, and transplantation. What have we learned for the new
      millennium.
AB  - The theory of hematopoiesis has been in existence for many years, providing the
      foundation for understanding the blood system and its development, and adding to
      the basic principles in the study of human development. As we enter the new
      millennium, we are able to use this groundwork of the hematopoietic system to
      further our research endeavors. It has provided the medical arena with the
      capability to expand and enhance treatment options for patients, and to explore
      further the vast possibility this system has to offer us beyond the year 2000.

PMID- 11847742
TI  - Training the client in self-management of hemophilia.
AB  - Hemophilia is an X-linked (or inherited) lifelong clotting disorder that affects
      approximately 1 in 7500 males. It is one of the eight most costly diseases to
      treat. True disease management can serve to ease and prevent physical
      complications while helping to control the financial burden. The rarity of
      hemophilia makes it difficult to find knowledgeable professionals who can assist
      patients on the road from total dependence to independence. This article will
      help readers to recognize key issues of the disorder and explain how clients can
      be assisted in working through the transitional process.

PMID- 11847744
TI  - Paradigms: a reprise.

PMID- 11847743
TI  - Blood transfusion knowledge and practice among nurses in Turkey.
AB  - This descriptive study was planned to identify blood transfusion practice and
      knowledge of 100 nurses from three hospitals in Ankara, Turkey. Data collected
      through observation and interviews were evaluated using percentages, chi 2, and
      correlation methods. Nurses' knowledge and practice related to blood transfusions
      were measured against a total score of 100. None of the participating nurses
      achieved a score of 100, and only a few had scores higher than 50. Although a
      positive correlation existed between the nurses' knowledge and practice scores,
      the correlation coefficient was insignificant. There was a statistically
      significant relation between the experience and knowledge scores, but not between
      the experience and practice scores. The results of the study showed insufficient
      knowledge about blood transfusion, which was reflected in undesirable practice.

PMID- 11847745
TI  - Nursing frameworks to guide practice and research with families: introductory
      remarks.

PMID- 11847746
TI  - Rogers' conceptual system and family nursing.

PMID- 11847747
TI  - Parse's human becoming school of thought and families.

PMID- 11847748
TI  - Family nursing: theory-anemic, nursing theory-deprived.

PMID- 11847749
TI  - Informed consent: process or outcome?

PMID- 11847751
TI  - Women of Hope--Tiospaye.

PMID- 11847750
TI  - Protecting human research subjects: an international perspective.

PMID- 11847752
TI  - Buying your life.

PMID- 11847753
TI  - Relational complexity: a theory of the nurse-patient relationship within an
      economic context.

PMID- 11847754
TI  - "Patchin' up the old wineskins": the challenge of crafting a science of healing
      practices in nursing.

PMID- 11847755
TI  - Role tuning between caregiver and care receiver during discharge transition: an
      illustration of role function mode in Roy's adaptation theory.
AB  - The purpose of this study was to develop a conceptual framework to explain the
      interaction between the caregiver and the care receiver during the discharge
      transition. Data from face-to-face interviews with 12 care receivers and 16
      caregivers were subjected to constant comparative analysis. Findings revealed
      that role tuning was the process used by caregivers and care receivers to achieve
      a harmonious pattern of caregiving and care receiving during the transition from
      hospital to home. This empirical finding can illustrate the concept of role
      function mode in the Roy adaptation theory and sensitize healthcare providers to
      the needs of the families during the discharge transition.

PMID- 11847756
TI  - The lived experience of feeling loved: a study of mothers in a parolee program.
AB  - The purpose of this study was to uncover the meaning of the lived experience of
      feeling loved. The site of this study was a shelter-based parolee program. The
      framework that guided the study was Parse's human becoming theory, and the method
      was Parse's research methodology. The finding of this study is the lived
      experience of feeling loved is an unshakable presence arising with moments of
      uplifting delight amid bewildering trepidation. The findings integrated into the
      human becoming theory show the paradoxical and dialectic nature of feeling loved.
      Feeling loved is linked to living freedom, trust, and hope.

PMID- 11847757
TI  - Violence against women: a worldwide problem.

PMID- 11847758
TI  - Female domestic violence victims: perspectives on emergency care.

PMID- 11847759
TI  - State of the Society. Intravenous Nurses Society.

PMID- 11847760
TI  - Does it always have to hurt? Premedications for adults and children for use with
      intravenous therapy.
AB  - Determining the need for premedication or anesthetic agent use in starting
      intravenous therapy should be considered a necessary step toward a successful
      i.v. procedure. This article discusses the types of premedications currently
      available for adults and children. Discussion of each anesthetic agent, its usage
      and limitations, and other pertinent information is given. Antianxiety agents are
      briefly discussed as an adjunct to anesthetics. Relaxation techniques of
      distraction and biofeedback to aid in the reduction of pain also can provide some
      degree of success for i.v. procedures. Not all i.v. procedures require
      premedications or anesthetic agents. Making the correct decision regarding which
      medication or antianxiety method best suits the patient and the situation can
      improve the overall success of and satisfaction with i.v. procedures.

PMID- 11847762
TI  - Activity restrictions in hospitalized patients with vascular access devices.
AB  - Hospitalized patients may require invasive vascular access. There are several
      types of vascular access; some have special activity restrictions. This article
      describes the types of vascular access the hospital caregiver may encounter and
      suggests conservative activity restrictions, which will assist the caregiver in
      planning care for the patient with invasive vascular access.

PMID- 11847761
TI  - The osmotic shift.
AB  - Water, the medium in which most cellular reactions take place, constitutes
      approximately 60% of the total weight in adults. This article discusses the
      complexities of shifts among the intravascular, interstitial, and intracellular
      compartments, and administration of hypotonic, isotonic, and hypertonic
      solutions.

PMID- 11847763
TI  - Intravenous complication: infiltration.
AB  - Infiltration often is viewed as a natural consequence of routine intravenous
      therapy. Subcutaneous infiltration of fluid is not always perceived as a serious
      problem. It is important for the clinician to be aware of the potential for
      injury as a result of medications or fluid leaking into the tissue. An
      infiltration is not the natural consequence of infusion therapy. Every effort
      should be made to ensure that the infusion will be completed safely without
      complication. The infusion specialist must use good judgment in site
      determination, device placement, securement, dressing, care, and maintenance.

PMID- 11847764
TI  - Devising an intravenous fluid therapy protocol and compliance of nurses with the
      protocol.
AB  - Although intravenous fluid therapy may be lifesaving if it is given properly,
      faulty application and inadequate care with this modality of treatment may lead
      to various complications. Many of these complications can be prevented by
      conducting the procedure in accordance with a standard protocol and with adequate
      care and monitoring. The aim of this study was to develop a protocol for
      intravenous fluid therapy and to determine whether the nurses observed the
      protocol. The study was done with 37 nurses working in a coronary care unit. The
      data were collected on a "Nurse Observation Form," and statistical evaluation,
      percentage, and the Cochran Q significance test were used. By the third
      observation, a higher percentage of nurses performed the procedures correctly,
      which indicated that implementation of the protocol had a positive effect.

PMID- 11847765
TI  - Nursing theories of caring. A paradigm for adolescent nursing practice.
AB  - In the past four decades, caring has emerged as a central paradigm in nursing.
      Caring as a central focus in nursing care of adolescents is developmentally
      appropriate and has been documented as the primary mechanism of effective health
      promotion for working with teens throughout the world. Other disciplines in
      adolescent health are beginning to realize the importance of caring therapeutics
      in practice, but nursing remains in the forefront of theory development and
      research in this area and is well positioned to provide leadership in further
      articulating caring theory within adolescent health care. Beyond theory
      development and testing, however, nurses need to include advocacy for the
      legitimacy and the importance of caring modalities in promoting the health of
      adolescents.

PMID- 11847766
TI  - The lived experience of using Watson's actual caring occasion to treat depressed
      women.
AB  - Each year, 19 million clients are treated for depressive episodes lasting 6 to 12
      months. With depression's economic costs between 16 to 43 billion dollars
      annually, managed care has reduced clinician time, currently averaging 25 minutes
      per visit. The purpose of this phenomenological study is to describe the
      essential structure of the lived experience of depressed women who enter therapy
      and experience Watson's actual caring occasion (ACO) within the transpersonal
      caring relationship (TCR). A purposive sample of 11 depressed women related their
      subjective experiences in therapy over 6 months. Spiegelberg's phenomenological
      method was used for data analysis of 110 pages of therapist's notes transcribed
      verbatim. Five essential themes emerged from data analysis. All participants
      stated Watson's ACO caused them to persist in treatment and adopt health-seeking
      behaviors. This finding supports the expense of appropriate clinician time for
      holistic healing in the TCR.

PMID- 11847767
TI  - Self-transcendence and family caregivers of adults with dementia.
AB  - Research has documented that caring for a family member with dementia is
      stressful and burdensome. However, difficult life experiences such as fear, loss,
      and grief may help persons move beyond a concern for self toward a larger
      perspective and concern for others. Both positive and negative experiences can
      promote positive movement toward growth and development. This movement has been
      described as self-transcendence, or the ability to look beyond the self and
      present difficulties, to extend concern to others, and to find personal meaning
      and wholeness in the context of life-changing events. The family caregiving
      experience with its inherent difficulties might provide the impetus for such a
      movement toward self-transcendence. The purpose of this article is to examine the
      concept of self-transcendence, explore its linkages to the caregiving experience,
      and suggest potential strategies to assist family caregivers to achieve self
      transcendence.

PMID- 11847768
TI  - The power of nurse-client encounters. Interpreting spiritual themes.
AB  - Both clients and caregivers are confronted with their own spiritual needs in the
      search for meaning within the health care experience. Yet, time for reflection on
      the powerful nature and mutuality of care giving is often crowded out by the
      busyness and intensity of health care. Using a guided reflection technique, 40
      nurse participants in five focus groups examined a written nurse-client
      encounter. Qualitative analysis of the merged data yielded five common themes and
      descriptive patterns: common elements in the encounter, descriptors portraying
      the encounter, meanings conveyed by the illness, spiritual needs uncovered, and a
      framework to apply to practice. Caregivers must be able to see illness as a
      meaning-intensive experience to be able to help clients understand their own
      spirituality. The reciprocity of the spiritual connection in health care
      encounters is proposed as a significant factor in renewal, satisfaction, and
      healing outcomes for both nurse and client.

PMID- 11847769
TI  - Adolescent use of alternative and complementary therapies. A framework for
      research.
AB  - Increasing numbers of U.S. adolescents are using alternative and complementary
      therapies, seemingly mirroring the trend among adults. Patterns of use among
      adolescents may be different from those of adults, however, due to the unique
      biological, psychological, and social factors affecting this population. Although
      there is a growing body of literature on utilization and efficacy of alternative
      and complementary therapies, few studies have included or focused on adolescents.
      Such research is needed. Social learning theory provides an appropriate
      theoretical framework to address the complex web of factors underlying health
      care-seeking behavior of adolescents, allowing for consideration of the critical
      factor of individual expectations in their health care choices. Research on
      adolescents' utilization of alternative and complementary therapies is important
      for providers and policy makers concerned with the present and future health of
      youth.

PMID- 11847770
TI  - Intentionality in holistic nursing.

PMID- 11847771
TI  - Acknowledging intuition in clinical decision making.
AB  - The purpose of this study was to develop and validate a scale to measure nurses'
      acknowledgment of using intuition in clinical decision making. Development and
      validation of the scale was carried out in three phases. In Phase 1, scale items
      were generated from the published literature in nursing and management and a
      Content Validity Index (CVI) of .96 was computed on responses from a panel of
      five experts. In Phase 2, the scale was pilot-tested on a random sample of 106
      psychiatric mental health nurses. In Phase 3, the revised scale was presented to
      a convenience sample of 112 nurses attending continuing education programs. Seven
      items were found to explain 40.6% of the variance in scores and were retained as
      the final unidimensional scale. Construct validity was supported by a difference
      in means of two groups that also differed on another measure of intuition.

PMID- 11847772
TI  - Nursing knowledge development through research: using the Roy adaptation model.
AB  - Almost half of the ancillary propositions tested in the metaparadigm category
      were related to the concept of person, and 94% were supported. Theoretically and
      empirically, there is support for Roy's conceptualization of the person as an
      adaptive system. Almost 25% of the ancillary propositions tested were related to
      the concept of health, of which the great majority were supported. Theoretically
      and empirically, there is support for Roy's conceptualization of health as an
      outcome of adaptation. Approximately 75% of the ancillary propositions tested
      were related to the concept of person or health. Of these, only 5 out of 55
      ancillary propositions were not supported, or less than 10%. Less than 13% of the
      ancillary propositions that were tested focused on the metaparadigm concepts of
      environment or nursing. Of these, 15% were not supported. These findings are not
      surprising, because conceptual clarity is the foundation of practice theory. The
      hierarchy of research, according to the classic work by Dickoff and James (1968),
      progresses from understanding and describing phenomena to situation-producing
      theory. Nursing models are relatively young. Research is required to validate the
      concepts within the models. Situation-producing theory, based on the concepts,
      guides nursing actions and is necessary for a practice discipline to maintain its
      status as a profession. Based on the findings of the integrative research review,
      adequate research has provided support for Roy's conceptualization of the
      metaparadigm concepts of person and health. Future research needs to be directed
      toward testing propositions derived from the RAM concepts of environment and
      nursing. Intervention studies need to be designed based on concepts that have
      been supported. Knowledge development through research and testing of
      propositions based on the RAM continues to contribute to nursing science. Future
      directions for RAM research are clear.

PMID- 11847773
TI  - A commitment to honoring people's choices.

PMID- 11847774
TI  - Growing story: a teaching-learning process.

PMID- 11847775
TI  - Becoming a bard: a journey to self.

PMID- 11847776
TI  - Into the new millennium.

PMID- 11847777
TI  - Comfort-discomfort with ambiguity: flight and freedom in nursing practice.

PMID- 11847778
TI  - An integrative framework for conceptualizing clients: a proposal for a nursing
      perspective in the new century.

PMID- 11847779
TI  - Response to Kim's human living concept as a unifying perspective for nursing.

PMID- 11847780
TI  - An empirical test of a self-care model of women's responses to battering.
AB  - A model of women's responses to battering was constructed based on Orem's theory
      of self-care deficit and on empirical and clinical observations. The model
      proposed that the age, educational level, and cultural influences as basic
      conditioning factors would all be directly related to relational conflict, which
      would be negatively related to self-care agency (as a mediator) and indirectly
      related to both outcomes of health and well-being. Using simultaneous structural
      equation modeling with specification searching, a modified model was derived that
      eliminated the mediation path but supported direct effects of both abuse and self
      care agency on health. The derived model was found to be only a borderline fit
      with the data, probably due to measurement problems, lack of inclusion of
      important variables, and small sample size (N = 117). However, there was support
      for several of the relationships deduced from and/or congruent with Orem's
      theory.

PMID- 11847781
TI  - A unitary view of persistence-change.

PMID- 11847782
TI  - The experience of caring for a loved one: a phenomenological study.
AB  - The purpose of this research was to uncover the meaning of caring for an elderly
      relative. Nine middle-aged and elderly people volunteered to take part in
      audiorecorded interviews to describe their experience of caring for a loved one.
      The following structural definition emerged from the study: The meaning of caring
      for an elderly relative is surfacing poignant remembering while doggedly
      continuing with nurturant giving and confirmatory receiving, as swells of
      enjoyment merge with tides of sorrow amid uplifting togetherness and valleys of
      aloneness. Parse's theory of human becoming and van Kaam's operations for
      phenomenological analysis are applied. Implications for practice and research are
      discussed.

PMID- 11847783
TI  - Leadership-scholarship integration: using the Neuman systems model for 21st
      century professional nursing practice.
AB  - This article describes leadership and scholarship from the Neuman systems model
      as requisite for a true practice model necessary for 21st-century scientific
      professional nursing. A rationale for the integration of leadership and
      scholarship is provided along with markers to guide the leadership-scholarship
      protocol, which can be viewed as a scholarly research process. An example from a
      community nursing center demonstrating the application of the integration of
      leadership-scholarship is presented to support the proposed integration.

PMID- 11847784
TI  - Transcending breast cancer, transcending death: a Taiwanese population.
AB  - This study explores transcendence as a lived experience through in-depth, face-to
      face interviews of 15 Taiwanese women with breast cancer. A phenomenological
      research method and Leininger's culture care theory were employed to guide the
      study. Four themes emerged as characteristic of the current lifeworlds of the
      study participants. The four themes are giving meaning to suffering, liberating a
      clinging nature, opening to life and death, and healing with compassion. The
      findings reveal that the essential structure of transcendence is the capacity of
      a person to give meaning to suffering, liberate self from a clinging nature, open
      self to life and death, and heal self with compassion.

PMID- 11847785
TI  - Case management: is it another passing fad?

PMID- 11847786
TI  - The road to professionalism in nursing: case management or practice based in
      nursing theory?

PMID- 11847787
TI  - A study within Newman's theory of health.

PMID- 11847788
TI  - Art as a path of inquiry.

PMID- 11847789
TI  - Possible outcomes of holistic nursing interventions.

PMID- 11847790
TI  - Spirituality, resourcefulness, and arthritis impact on health perception of
      elders with rheumatoid arthritis.
AB  - Arthritis is the leading chronic condition for older adults and the leading cause
      of disability in the United States. Providing holistic care to promote positive
      health perception and support healthy lifestyle decisions with these individuals
      is critical in attaining and maintaining quality of life. This study examined
      variables reflecting reactions to stress, lines of defense and resistance, and
      the basic core of humans in the context of the Neuman Systems Model in a
      convenience sample of 47 adults with a mean age of 70.4 years. The combined
      effects of the social, emotional, and physical impact of arthritis and additive
      or mediating effects of learned resourcefulness and spirituality on general
      health perception in older adults were investigated. Social, emotional, and
      physical impact together predicted health perception. The social impact of
      arthritis was a significant independent predictor for spirituality. Furthermore,
      spirituality and health perception were significantly correlated.

PMID- 11847791
TI  - The prevalence of prayer as a spiritual self-care modality in elders.
AB  - The purpose of this cross-sectional, descriptive study was to (a) investigate
      whether elders report using prayer as a coping strategy, (b) examine the
      frequency and type of spiritual treatment modalities used by elders, and (c)
      determine if there is a relationship between spiritual treatment modalities and
      coping in this population. The sample consisted of 50 community-dwelling elders
      with a mean age of 74 years. Descriptive findings indicate that 96% of elders use
      prayer to cope with stress based on the Jalowiec Coping Scale. Women and Blacks
      used prayer to cope with stress significantly more often than did men and Whites.
      The most frequently reported alternative treatment modality was prayer (84%). The
      total number of spiritual treatment modalities reported was significantly
      correlated with the frequent use of more positive coping styles.

PMID- 11847792
TI  - Comprehensive versus holistic care. Case studies of chronic disease.
AB  - Persons with chronic disease often experience an involvement of multiple body
      systems. A comprehensive care approach to patient care is often used with the
      belief that a health care team will ensure that a patient's needs will be
      covered. Instead, this approach is reductionist in practice and leads to
      fragmentation of care, and the difficult patients often slip through the cracks
      of the health care system. However, a holistic theory-based approach puts a
      patient's perceived needs first and offers care not only for the body but also
      for the human spirit. Two case studies of patients with chronic disease are
      reviewed, both of whom began in a comprehensive care model and ended up with
      holistic care. Suggestions for assisting in the movement of a comprehensive care
      model toward a holistic model are offered for the practicing nurse.

PMID- 11847793
TI  - Construct analysis of four modes of being present.
AB  - The purpose of this construct analysis is to delineate the manner or modes of
      presence as used by nurses with their patients. The scope of the term presence
      encompasses four separate, distinct modes of presence. The term concept does not
      encompass the scope of the term. Therefore, the term construct is applied to
      demonstrate the differences in the four modes of being present. Model cases were
      extrapolated from personal experiences. Methods used in the construct development
      and construction include components of the Wilsonian method, an evolutionary
      view, and the hybrid model. Due to the breath and complexity of the
      interrelatedness of the four modes of being present, the author presents only a
      model case. To illustrate the attributes and consequences for the patient and the
      nurse in the interpersonal relationship for each of the four modes of being
      present, the author created models.

PMID- 11847795
TI  - Language: words reflect and cocreate meaning.

PMID- 11847794
TI  - The lived experience of listening to music while recovering from surgery.
AB  - Music has been shown to have positive physiological and psychological effects on
      patients in previous studies. In this study, the authors looked at the lived
      experience of listening to music and evaluated findings from a phenomenological
      perspective. Specifically, the authors described the following three themes that
      emerged from interview data with 8 participants who listened to music during
      postoperative recovery: (a) comfort from a discomforting condition, (b)
      familiarity in a strange environment, and (c) distraction from fear, pain, and
      anxiety. In addition, implications for the use of music by nurses are discussed.

PMID- 11847796
TI  - Nursing science frameworks for practice and research as means of knowing self.

PMID- 11847797
TI  - Rogerian nursing science and research: a healing process for nursing.

PMID- 11847798
TI  - Nurse as patient advocate? In search of straight thinking.

PMID- 11847799
TI  - Dialogue: a process of structuring meaning.

PMID- 11847800
TI  - Situated immersion: an experience of dialogue.

PMID- 11847801
TI  - Patient-focused care and human becoming thought: connecting the right stuff.

PMID- 11847802
TI  - Toward a complementary perspective on worldviews.
AB  - In this column, it has been argued that fragmentation of knowledge in nursing
      science can be related to the dominant way of thinking of worldviews as
      competitive dualities. To move toward resolving that conflict, the thesis has
      been set forth to claim that a complementary perspective on worldviews as an
      ontological framework can promote knowledge synthesis and alternative thinking
      methods in nursing science. Implications of the potential for a complementary
      perspective for encouraging integrative and creative thinking for professional
      nursing practice has been presented.

PMID- 11847803
TI  - Changes in hope and power in lung cancer patients who exercise.
AB  - Using Rogers' science of unitary human beings, changes in hope and power among
      104 lung cancer patients were examined in relation to participation in a
      preoperative exercise program. Participants were randomly assigned to exercise or
      no-exercise and a repeated measures ANOVA was employed. The exercise group's
      power increased while the no-exercise group's power decreased. No differences in
      hope emerged. Positive correlations between hope and power were observed.
      Findings suggest that exercise is a form of knowing participation in change and
      illustrate a relation between one's ability to envision a better future and one's
      potential to actualize options through choice.

PMID- 11847804
TI  - A nursing theory of personal system empathy: interpreting a conceptualization of
      empathy in King's interacting systems.
AB  - This article presents a theory of empathy discovered through rational hermeneutic
      interpretation within King's personal system. Personal system concepts from
      King's general systems framework include perception, self, growth and
      development, body image, space, time, and learning. Propositions for each concept
      in the personal system were explicated and a theory of nursing empathy was
      developed. This nursing theory proposes that empathy organizes perceptions;
      facilitates awareness of self and others; increases sensitivity; promotes shared
      respect, mutual goals, and social awareness; cultivates understanding of
      individuals within a historical and social context; and affects learning.

PMID- 11847805
TI  - Developing a concept of hope from a human science perspective.
AB  - This article explores concept development from a human science perspective and
      uses concept inventing, a method described by Parse, for developing the concept
      of hope as inspired by the Taiwanese folk song "Mending a Torn Fish Net." The
      synthesized definition is hope is resolute picturing of the possibilities amid
      the restrictions-opportunities of communion-aloneness while creatively
      metamorphosing. This definition is explicitly connected to the three principles
      of Parse's theory of human becoming. Reflections on research and practice are
      provided.

PMID- 11847806
TI  - A meta-analysis of the interrelationships between the modes in Roy's adaptation
      model.
AB  - A meta-analysis of nine empirical studies based on Roy's adaptation model was
      conducted to determine the magnitudes of the interrelationships of the four
      modes: physiological, self-concept, role function, and interdependence. Small to
      medium effect sizes between each two modes do support the proposition of Roy's
      model that the four modes are interrelated. The only exception is the
      relationship between interdependence and physiological modes, as shown by the non
      significant effect size of .04. The present study also discusses several
      limitations that should be considered when interpreting the findings of this meta
      analysis. This study does provide a useful compilation of the Roy model's
      credible studies and proposes a direction for further research. The results
      indicate a need for further study to explore the relationship in all response
      modes to have a clearer understanding of the credibility of Roy's model.

PMID- 11847807
TI  - The role of nursing theory in standards of practice: a Canadian perspective.

PMID- 11847808
TI  - Nursing theory in education, practice, and research in Sweden.

PMID- 11847809
TI  - Cultural competence in holistic nursing.

PMID- 11847810
TI  - A review of the concept of culture in holistic nursing literature.
AB  - Core Value IV of the American Holistic Nurses' Association includes valuing the
      client's cultural background. The authors reviewed all article abstracts from two
      major holistic nursing journals for a 3-year period (N = 198). References to
      concepts of culture or ethnicity were found in only 9.6% of abstracts. Many
      theorists and researchers did not discuss how the theory or research findings
      varied between culturally or ethnically diverse samples. When culture is a core
      value, practitioners and researchers cannot assume that culture has been
      considered without stating what was the interaction of culture with the
      phenomenon of concern. The authors recommend that nurses develop cultural
      competence in caring for clients from differing cultural orientations by (a)
      committing to improve their knowledge of multiple cultures; (b) exploring their
      own cultural background; (c) seeking exposure to cultures other than their own;
      and (d) regularly discussing culture and ethnicity in nursing theory, research,
      and practice.

PMID- 11847811
TI  - Ecospirituality. A pattern that connects.
AB  - Ecospirituality is a manifestation of the spiritual connection between human
      beings and the environment. Ecospirituality incorporates an intuitive and
      embodied awareness of all life and engages a relational view of person to planet,
      inner to outer landscape, and soul to soil. This study describes an appraisal of
      a pattern in the human-environmental, continuous mutual process and innovative
      change; a phenomenological study that used the focus group method. Randomly
      selected volunteer registrants (n = 36) of phase one of the American Holistic
      Nurses' Association Certificate Program in Holistic Nursing constituted the
      sample and participated in one of four focus groups. The findings of this study
      contribute to holistic nursing by examining the essence of the lived experience
      of an ecospiritual consciousness of select holistic nurses. The essences of an
      ecospiritual consciousness are uniquely inseparable entities embedded within the
      framework of an ecospiritual consciousness. The essences are tending, dwelling,
      reverence, connectedness, and sentence.

PMID- 11847812
TI  - Cultural differences in music chosen for pain relief.
AB  - Nurses use music therapeutically but often assume that all patients will equally
      appreciate the same type of music. Cultural differences in music preferences are
      compared across five pain studies. Music preferences for pain relief are
      described as the most frequently chosen type of music for each culture. Findings
      indicate that in four studies, musical choices were related to cultural
      background (p = .002 to .049). Although the majority in each group chose among
      the other types of music, Caucasians most frequently chose orchestra music,
      African Americans chose jazz, and Taiwanese chose harp music. For culturally
      congruent care, nurses should become aware of cultural differences in music
      preference and provide culturally specific selections among other music expected
      to have a therapeutic effect.

PMID- 11847813
TI  - The lived experience of Ojibwa and Cree women healers.
AB  - The purpose of this phenomenological research study was to describe the meaning
      and essence of the lived experience of Ojibwa and Cree women healers. The
      research question, "What is the experience of being an Ojibwa or Cree woman
      healer?" was asked of a purposive sample of four indigenous women healers, aged
      48 to 59, residing in Canada and the United States. The data were collected and
      analyzed utilizing methods to preserve integrity within the indigenous community.
      Seven themes emerged from the data. They are as follows: recognizing and
      unfolding the healing gift; placing faith in the healing ability; mastering
      indigenous culture, values and traditions; wholesome use of self; interconnection
      with all; living a balanced, circular life way; and embracing mankind. These
      seven themes can be employed by nurse healers and/or holistic nurses to practice
      the art of holistic nursing.

PMID- 11847814
TI  - A comparison of the use of alternative therapies among Mexican Americans and
      Anglo-Americans in the Texas Rio Grande Valley.
AB  - In a descriptive study with a convenience sample of 60 Mexican Americans and 60
      Anglo-Americans, four research questions were asked: (a) What kinds of and how
      frequently are alternative therapies used by the Mexican Americans and Anglos in
      the Texas Rio Grande Valley? (b) Is there a difference in the kinds and amounts
      of therapies used by the two groups? (c) Do the participants self-report this
      information to their established, conventional, care provider? and (d) What are
      the participants' subjective reports about these therapies? Findings showed that
      both groups used alternative practitioners, but that Mexican Americans reported
      using them more than twice as often as did Anglo-Americans. The most prevalent
      therapies sought by Mexican Americans were prayer, herbal medicine, massage,
      relaxation, spiritual healing, and chiropratic. The most prevalent therapies
      sought by Anglo-Americans were prayer, massage, chiropractic, herbal medicine,
      megavitamin therapy, and spiritual healing. Almost twice as many Mexican
      Americans (45%) report discussing their therapies with their established primary
      health provider than did Anglos (26.7%).

PMID- 11847815
TI  - The cost of breastfeeding support: a primer.

PMID- 11847816
TI  - Breastfeeding and WIC ... are they indeed mutually exclusive? Not in my
      experience.

PMID- 11847817
TI  - Breastfeeding peer counseling: policy implications.

PMID- 11847818
TI  - Response to "an open letter to the WIC program: the time has come to commit to
      breastfeeding".

PMID- 11847819
TI  - Author's response to "Breastfeeding and WIC ... are they indeed mutually
      exclusive? Not in my experience".

PMID- 11847820
TI  - Formula feeding is encouraged here.

PMID- 11847822
TI  - Supplementation in the hospital setting.

PMID- 11847821
TI  - The treatment of Staphylococcus aureus infected sore nipples: a randomized
      comparative study.

PMID- 11847823
TI  - Breastfeeding on airlines.

PMID- 11847824
TI  - Safety of hydrogel dressings.

PMID- 11847825
TI  - Breastfeeding peer counseling: results from the National WIC Survey.
AB  - The objective of this study was to examine breastfeeding peer counseling within
      the context of the organizational structure of state and local Supplemental
      Nutrition Program for Women, Infants and Children (WIC) agencies. The National
      WIC Breastfeeding Peer Counselor Survey was distributed to a convenience sample
      of state WIC breastfeeding coordinators and breastfeeding project coordinators
      and to a sample of local agency WIC directors and staff, breastfeeding peer
      counselor coordinators, and peer counselors. The findings indicate that
      respondents in the WIC state and local organizations perceive peer counseling to
      be effective in promoting and sustaining breastfeeding among WIC mothers. There
      is, however, a lack of consistent policies and procedures concerning the
      recruitment, training, and counseling phases of peer counseling within and across
      state WIC agencies.

PMID- 11847826
TI  - Randomized study comparing the efficacy of a novel manual breast pump with a mini
      electric breast pump in mothers of term infants.
AB  - The objective of this study was to compare the efficacy of a mini-electric pump
      (MEP) and a novel manual breast pump (MP) designed to operate more
      physiologically. Sixty term breastfeeding mothers used the MP and MEP in
      randomized order 8 weeks postpartum, expressing for 10 minutes from each breast.
      Milk volume, fat content, and pattern of milk flow were measured. Mothers rated
      pump characteristics by questionnaire. There was no significant difference in the
      milk volume or fat content when mothers used the pumps in randomized order. The
      MP was rated significantly better overall and more comfortable and pleasant to
      use. Significantly more mothers kept the MP than the MEP. Despite the greater
      complexity and expense of the MEP, the pumps showed similar efficacy. The MP was
      preferred by mothers. The novel, more physiological operation of the MP
      represents an advance in milk expression technology.

PMID- 11847827
TI  - Breastfeeding peer counseling: rationale for the National WIC Survey.
AB  - Peer counseling has been recognized as an effective intervention in the promotion
      of breastfeeding among low-income women. This paper provides a literature review
      demonstrating the effectiveness of peer counseling in health care settings,
      especially those concerned with breastfeeding. In addition, barriers identified
      in the literature that limit the integration of peer counseling in medical
      settings are examined. The need for The National WIC Breastfeeding Peer Counselor
      Survey and background information on this survey are also discussed.

PMID- 11847828
TI  - Wet nursing 2001: old practice, new dilemmas?

PMID- 11847830
TI  - Sensory defensiveness: a theory of its effect on breastfeeding.
AB  - This article describes one type of sensory integrative disorder: sensory
      defensiveness. An examination of the possible relationship of this disorder to an
      infant's difficulties with breastfeeding is conducted. A family case study is
      detailed, followed by treatments implemented by the authors. Possible long-term
      sequelae, as well as the need for more interdisciplinary research, are discussed.

PMID- 11847831
TI  - Donor milk: what's in it and what's not.
AB  - Breastfeeding and human milk are widely recognized as optimal for human infants.
      However, if donor milk is used when mother's own milk is not available, some
      questions arise concerning the effects of storage, handling, and heat processing
      on the unique components of human milk. Holder pasteurization (62.5 degrees C for
      30 minutes) of banked human milk is the method of choice to eliminate potential
      viral contaminants such as human immunodeficiency virus, human T-lymphoma virus,
      and cytomegalovirus, as well as tuberculosis and other bacterial contaminants,
      while maintaining the greatest possible complement of its unique bioactive
      factors. This article reviews some of the critical components of human milk and
      what is currently known about the effects of Holder pasteurization on their
      biological activity.

PMID- 11847829
TI  - Disruption of lactogenesis by retained placental fragments.
AB  - This case report describes a situation in which lack of milk production led the
      mother to seek help from a lactation consultant in private practice. Despite
      extensive breast stimulation with the baby at breast and mechanical breast
      expression, no milk was produced. Retained placenta was suspected by the
      lactation consultant. The mother was later diagnosed with placenta increta. Only
      when this condition was diagnosed and resolved did milk onset occur. It is
      important to evaluate for retained placental fragments when lactation appears to
      be delayed.

PMID- 11847832
TI  - Statistical report of the 2000 IBLCE examination.

PMID- 11847833
TI  - Use of anti-infective agents during lactation, Part 3: Antivirals, antifungals,
      and urinary antiseptics.
AB  - Because many antibiotics are excreted into the breast milk, it can be difficult
      for a practitioner to choose an antibiotic for a lactating patient that will have
      minimal risks to her nursing infant. This article is the last of a three-part
      series discussing the use of anti-infective agents during lactation. The authors
      review general information with regard to use and common side effects for several
      classes of antibiotics. They summarize information, including available safety
      data, documented milk concentrations, milk-to-plasma ratios, and other
      pharmacokinetic properties, to help practitioners choose antibiotics that may be
      considered safe to use in the lactating mother.

PMID- 11847834
TI  - The family as a protective asset in adolescent development.
AB  - Adolescents are considered at high risk for engaging in such negative health
      behaviors as drug and alcohol use, unprotected sexual intercourse, and violence.
      Conventional wisdom has long upheld the belief that the peer group exerts the
      strongest influence on adolescent behavior. However, recent research has shown
      that in fact the family remains a strong factor in moderating teen risk behavior.
      Holistic nursing acknowledges the crucial relationship between environment and
      health; the environment is composed of everything that surrounds the individual,
      which by definition includes the family. The purpose of this article is to
      examine the evidence supporting the concept of the family as a protective
      external asset in adolescent development, to explore the way the family helps
      defend young people from risk, and to review briefly the implications for nursing
      research, practice, advocacy, and education.

PMID- 11847835
TI  - The lived experience of college student lesbians' encounters with health care
      providers. A preliminary investigation.
AB  - The purpose of this preliminary study was to explore the lived experience of four
      self-identified college student lesbians coming out and their encounters with
      health care providers. This study used a qualitative method of phenomenology for
      data collection and analysis. Results of the study revealed a phenomenological
      model that embodied the core theme of navigating self-disclosure. Two major
      themes stemming from the core theme were also uncovered. Navigating self
      disclosure in homophobic waters and navigating self-disclosure encounters with
      health care providers unveiled a continuum of self-disclosure to nondisclosure
      experiences encountered by lesbians. Strategies are offered to enhance
      interactions between lesbians and health care providers in primary and acute care
      settings.

PMID- 11847836
TI  - Adolescent violence. Assessment of nurses' attitudes and educational needs.
AB  - Adolescent violence is a major public health problem. Because of their roles in
      community and hospital settings, nurses have an opportunity to limit the epidemic
      of violence. The purpose of this study was to examine the perceived levels of
      knowledge, the value of further education, resource utilization, and attitudes of
      nurses caring for adolescent victims of violence. Data were collected from 60
      nurses employed at an urban public hospital. Results of the study indicate that
      50% of the respondents had high scores on the perceived knowledge section of the
      survey. However, the majority of nurses (82.5%) felt inadequately educated about
      violence. The attitudes reported with the most frequency were frustration (78%),
      anger (59%), and powerlessness (58%). The results of this study indicate a need
      for additional violence education for nurses, particularly in the areas of
      available resources and intervention for adolescent victims of violence.

PMID- 11847837
TI  - A theory of healing in the aftermath of youth suicide. Implications for holistic
      nursing practice.
AB  - The purpose of this family-focused, grounded-theory study was to develop a
      substantive theory that explains how individual family members heal in the
      aftermath of youth suicide. Individual healing following youth suicide is
      conceptualized as a process of "journeying toward wholeness." In response to
      youth suicide, survivors characteristically tap into their innate strengths and
      coping capabilities. Eventually, most survivors move toward healing. Precipitated
      by youth suicide, individual healing was found to be a contextually mediated,
      ongoing, dynamic, and recursive process. Most often initiated by a family
      survivor who was emotionally and spiritually close to the youth prior to suicide,
      healing emanated from the survivor's consciousness as an act of volition. This
      study brings to light the idea that bereaved family survivors of youth suicide
      have the potential to heal in response to the decisions they make and the healthy
      bonds they create and maintain between themselves and the deceased youth.

PMID- 11847839
TI  - Applied concepts of holistic nursing.
AB  - Meeting the many needs of a young adolescent on a busy Saturday can be quite a
      challenge. This article shows how a nurse practitioner drew on Watson's theory of
      caring as the basis of her interaction with an 11-year-old boy and his mother and
      relied on her ability to be flexible and creative in the process. The positive
      outcomes of this visit were evident in the client's and mother's change of affect
      and their commitment to take positive action. the nurse practitioner experienced
      renewal of spirit and a sense of gratitude for the effective role she played in
      this interaction.

PMID- 11847838
TI  - Voices of hope. Hearing and caring for Haitian adolescents.
AB  - Although much research has been conducted on the effects of migration on the
      psychosocial evolution of various ethnic groups, only limited information exists
      about the meaning of migration for Haitian adolescents. Haitian adolescents, in
      addition to experiencing the trials of adolescence, often feel a sense of loss
      and confusion when they are forced to leave their homeland. This phenomenological
      study focuses on the experience of being a Haitian adolescent living in South
      Florida. Six Haitian adolescents were both interviewed and asked to produce
      writing about their experiences and perception of self-identity. Their responses
      evaluated in light of Piaget, Erickson, and Sullivan illustrated eight themes
      defining the adolescents' senses of identity: pride, isolation, prejudice,
      parental strictness, nostalgia, belonging, familism, and career vision. The
      insights acquired through this study have practical applications in designing
      more effective caring strategies, in advocating for clients, and in delivering
      culturally competent holistic nursing care.

PMID- 11847840
TI  - Focusing on protective resources in adolescent health care.

PMID- 11847841
TI  - Ethical principles applied to complementary healing.
AB  - With the public and professional shift to an interest in
      alternative/complementary therapies and holistic health, existing assumptions
      about the relationship between providers and clients are being challenged. This
      study explores the ethical approaches and underlying principles in the
      expectations of three organizations espousing holistic health and touch
      therapies. An analytic technique using a qualitative approach was applied to the
      documents of written ethical codes and standards from these organizations and was
      augmented by field exposure from previous work with each of the groups of
      healers. The emphasis on and approach to the principles of paternalism and
      autonomy from the groups provided contrasts with general biomedical approaches.
      All groups gave attention to the constructs of nonmaleficence, beneficence, and
      autonomy, with a strong emphasis on virtue ethics. The shift in the expression of
      the principles of paternalism and client agency allowed the healers to employ the
      therapeutic effects of placebo, suggestion, optimism, hope, and surrender with
      the avoidance of noicebo effects.

PMID- 11847842
TI  - Nurses' attitudes toward survivors and perpetrators of domestic violence.
AB  - Domestic violence is of special concern to nurses, as they are often the first
      health care professionals to interact with battered women. The purpose of this
      study was to explore and describe nurses' attitudes toward the survivors and
      perpetrators of domestic violence. A holistic ecological health promotion
      framework guided this qualitative investigation. Thirteen participants expert in
      the care of abused women were interviewed using semistructured questions to
      describe nurses' attitudes toward survivors and perpetrators. Significant
      statements were identified, clustered, and placed into categories of response.
      Findings included identification of general themes and specific categories
      related to attitudes nurses have about battered women and those who abuse and
      injure them. The significance of this research underscores the importance of
      nurses' attitudes as influencing factors in their interactions with women and
      families involved in domestic violence. Application of a health promotion
      framework encourages a holistic perspective of care for this vulnerable
      population.

PMID- 11847843
TI  - A holistic approach to promoting success on NCLEX-RN.
AB  - The nursing faculty at the State University of West Georgia views individuals as
      an integration of body-mind-spirit. Our program's commitment complements efforts
      to teach students to honor the body, mind, and spirit of patients. Within this
      framework, faculty recognize that factors other than nursing knowledge impact
      students' ability to pass NCLEX-RN. An intervention program was designed that
      incorporated these factors. "Preparation for Licensure" was implemented as a
      holistic nursing course to intervene with students' learning and testing needs.
      The purpose was to increase self-awareness, promote a positive attitude toward
      passing the NCLEX-RN, and provide specific strategies for test taking and stress
      reduction. Posttest raw scores and percent correct on the Mosby Assess Test were
      significantly higher (p < .05) than pretest scores. Qualitative analysis of
      journal data exploring the students' experience of participating in the course
      revealed three themes: Perfectionism, Self-Worth, and Consequences and Meaning of
      Failure.

PMID- 11847844
TI  - The holism in critical thinking. A concept analysis.
AB  - In nursing, critical thinking is particularly important because of its potential
      impact on patient care. With the rapid changes in health care and the influx of
      new technology, nurses must be able to use critical thinking to make decisions
      that provide optimal patient care. The rapid, dynamic changes occurring in the
      health care setting have dictated a stronger, more comprehensive, holistic way of
      arriving at decisions than the traditional nursing process. This more
      comprehensive, holistic approach is called critical thinking. Nurses must be able
      to engage in critical thinking to handle the onslaught of continuous procedural
      and technological changes. Critical thinking has become such a key component in
      learning that the National League for Nursing requires that graduates be able to
      demonstrate critical thinking. This article is a concept analysis of critical
      thinking using the Walker and Avant model.

PMID- 11847845
TI  - The use of holistic concepts in professional practice.
AB  - This article describes a caring interaction between a nurse and a client in
      emotional distress in the emergency department. The author demonstrates the use
      of holistic concepts such as self-care, self-awareness, intention, presence,
      imagery, and rituals in her relationship with the client.

PMID- 11847846
TI  - "Breast is best": knowledge among low-income mothers is not enough.
AB  - The beliefs of low-income mothers regarding breastfeeding compared to formula
      feeding, according to feeding method, were investigated. Interviews were
      conducted with 154 women who were assigned to one of two groups. Four health
      benefits of breastfeeding were rated significantly higher than for infant formula
      within both the breastfeeding (BF) and formula-feeding (FF) groups. Breastfeeding
      was seen as less convenient than formula feeding by the FF group (mean = 2.3 +/-
      1.7 versus 3.8 +/- 1.5 for formula feeding and breastfeeding, respectively; P <
      .001). Both groups rated formula feeding as more likely to enable others to help
      in infant care, easier in terms of the mother's time control, and less likely to
      tie mother down than breastfeeding. The findings show that, despite formula
      feeding mothers' beliefs in the health benefits of breastfeeding, they perceive
      that it limits their activities. Therefore, breastfeeding promotion must address
      not only benefits but also lifestyle issues.

PMID- 11847848
TI  - Psychosocial factors associated with the abandonment of breastfeeding prior to
      hospital discharge.
AB  - A prospective study of 556 women from Perth, Western Australia, and 503 women
      from the Darling Downs area, Queensland, Australia, was conducted to identify
      factors associated with the abandonment of breastfeeding prior to hospital
      discharge. In total, 88% of women initiated breastfeeding, but 5% discontinued
      breastfeeding while still in the hospital. Discontinuation of breastfeeding prior
      to discharge was associated with a number of psychosocial factors, namely, infant
      feeding method being chosen after becoming pregnant, a perception by the mother
      that the infant's father either preferred formula feeding or was ambivalent about
      how the infant was fed, and whether the mother's own mother had ever breastfed.
      Judicious questioning prenatally regarding a women's commitment to, social
      support for, and prior exposure to breastfeeding will help identify those women
      most at risk of abandoning breastfeeding prematurely. Such women should be
      targeted for additional support while in the hospital.

PMID- 11847847
TI  - Predicting breastfeeding duration using the LATCH breastfeeding assessment tool.
AB  - The authors tested the validity of the LATCH breastfeeding assessment tool,
      controlling for intervening variables in 133 dyads. LATCH scores, mother's
      evaluation of an index feed, and intended duration of breastfeeding were assessed
      postpartum and followed 6 weeks. Women breastfeeding at 6 weeks postpartum had
      higher LATCH scores (mean +/- SD = 9.3 +/- 0.9) than those who weaned (mean +/-
      SD = 8.7 +/- 1.0), due to only one measure, breast/nipple comfort. Women who
      weaned before 6 weeks reported lower breast/nipple comfort (1.5 +/- 0.5) than
      those who were still breastfeeding at 6 weeks (1.7 +/- 0.5, P < .05). Total LATCH
      scores accounted for 7.3% of variance in breastfeeding duration. Total LATCH
      scores positively correlated with duration of breastfeeding (n = 128; r = .26, P
      = .003) and to mothers' scores (n = 132; r = .58, P = .001). Correlations among
      LATCH measures ranged from .02 to .51. The LATCH tool is a useful identifies the
      need for follow-up with breastfeeding mothers at risk for early weaning because
      of sore nipples.

PMID- 11847849
TI  - Women's experiences breastfeeding in public places.
AB  - This two-part field study compared researchers' recorded observations to mothers'
      perceptions of attention they received while publicly breastfeeding. In part 1,
      four breastfeeding and four bottle-feeding mothers each made eight restaurant
      visits. On average, there were more neutral looks from customers (P = .01) during
      breastfeeding visits, but no differences in the amount of overtly negative or
      positive attention given during breastfeeding versus bottle feeding. In part 2,
      four breastfeeding mothers made a total of 24 visits to shopping malls. There
      were more neutral looks given while mothers were breastfeeding and more smiles
      and comments while they were not feeding, but no difference in total amount of
      attention received. Breastfeeding mothers acknowledged they had anticipated some
      undesirable attention but instead received little attention. Nevertheless, they
      felt "vulnerable" nursing in public. Certain proactive behaviors and personal
      attributes as well as support from other women enabled them to breastfeed
      successfully in public.

PMID- 11847850
TI  - Exploring large employers' and small employers' knowledge, attitudes, and
      practices on breastfeeding support in the workplace.
AB  - Human resource professionals from different industries participated in focus
      groups in Austin, Texas. From a social marketing perspective, employers'
      knowledge, attitudes, and practices in providing breastfeeding support for
      lactating employees were explored. Employers knew about the benefits of
      breastfeeding for mothers and children. However, they did not place a high
      priority on providing breastfeeding support. Employers identified the barriers to
      and motivators for providing breastfeeding support, as well as effective
      communication and marketing strategies for the dissemination of breastfeeding
      support messages and materials for employers. Participants revealed important
      employer variables, such as the size of the company or agency, that must be
      considered when designing social marketing campaigns that target employers. This
      research provided in-depth, qualitative data useful for designing social
      marketing campaigns that target employers and for further investigation using
      qualitative and quantitative research methods.

PMID- 11847851
TI  - Case management of a premature infant transitioning to the breast.

PMID- 11847852
TI  - Letting perfect get in the way of good.

PMID- 11847853
TI  - Excelencia em bancos de leite humano: uma visao do futuro--the First
      International Congress on Human Milk Banking.
AB  - The first International Congress of Human Milk Banks--Excellence in Human Milk
      Banking: A Vision of the Future, held in Brazil in June 2000 and sponsored by the
      Brazilian Association of Milk Banks, had representation from milk banks in
      Argentina, Chile, Costa Rica, Venezuela, France, the United Kingdom, and North
      America as well as Brazil. A recurring theme in the discussion of donor milk
      banking was the role of each country's milk banks in the promotion and support of
      breastfeeding. The Brazilian National Reference Milk Bank and the growth of donor
      milk banking in Brazil over the past 15 years were described, including federal
      regulation that all milk bank directors be trained and certified. Milk banking
      systems in France, the United Kingdom, Venezuela and the Caribbean, and North
      America were also discussed. Similarities and differences in the donor screening
      process and the regulation of milk banks in the countries is presented.

PMID- 11847854
TI  - Use of anti-infective agents during lactation: Part 2--Aminoglycosides,
      macrolides, quinolones, sulfonamides, trimethoprim, tetracyclines,
      chloramphenicol, clindamycin, and metronidazole.
AB  - Because many antibiotics are excreted into breast milk, it can be difficult for a
      practitioner to choose an antibiotic for a lactating patient that will have
      minimal risks to her nursing infant. This article is the second of a three-part
      series discussing the use of anti-infective agents during lactation. The authors
      review general information regarding use and common side effects for several
      classes of antibiotics. They also summarize information, including documented
      milk concentrations, milk-to-plasma ratios, and other pharmacokinetic properties,
      in a table that can help practitioners choose antibiotics that may be considered
      safe to use in the lactating mother.

PMID- 11847855
TI  - Response to "An open letter to the WIC program".

PMID- 11847857
TI  - Supplementation in the hospital setting: a response to Johanna Gorab's letter.

PMID- 11847856
TI  - Circumcision and breastfeeding: a response to Nikki Lee's letter.

PMID- 11847858
TI  - Initiation and frequency of pumping and milk production in mothers of non-nursing
      preterm infants.
AB  - This secondary data analysis examined if time of initiation of milk expression
      and pumping frequency influenced milk weight weeks 2-5 postpartum. Of the 39
      subjects in the convenience sample, 20 were in the early initiating (EI) group,
      (n = 12 high frequency [HF], n = 8 low frequency [LF]), and 19 were in the late
      intiating (LI) group, (n = 7 HF, n = 12 LF). The EI group initiated pumping < or
      = 48 hours after birth; the HF group pumped a minimum of 6.25 times daily. A two
      way analysis of variance indicated that milk weight was significantly higher in
      the HF as compared to the LF group. While there was no significant difference in
      milk weight between the EI and LI groups, there was a significant interaction
      between frequency and initiation. Milk weight for the LF/EI group appeared to be
      positively influenced by the initiation of mechanical expression soon after
      birth.

PMID- 11847859
TI  - Reprocessing of single-use endoscopic biopsy forceps and snares. One hospital's
      study.
AB  - Financial pressures imposed on hospitals by health maintenance organizations and
      insurers have prompted investigation into alternative procedures that reduce
      expenses while maintaining the high standards required for patient care. Although
      not necessarily mutually exclusive, these dual agendas pose a challenge for
      endoscopy managers charged with balancing the risks and benefits of reusable and
      disposable endoscopy instruments. Our endoscopy unit elected to evaluate the
      feasibility of reducing costs by using reprocessed single-use devices. Following
      the selection of a third party reprocessor and prior to using any reprocessed
      devices in the clinical setting, our facility decided to submit single use
      devices that had been used once for reprocessing and then have an independent
      laboratory test them for sterility. Although we followed a thorough, multi
      disciplinary approach, our end result led us to conclude that the cleaning,
      reprocessing, and resterilization of single-use biopsy forceps and snares is a
      greater challenge than previously anticipated. Reprocessing of the single-use
      devices tested did not result in endoscopic instruments that met acceptable
      standards for sterility at our institution.

PMID- 11847860
TI  - Flexible endoscopes: structure and function. The suction and biopsy channel.
AB  - Flexible endoscopes are complex medical instruments that are easily damaged. To
      maintain the flexible endoscope in optimum working condition, the user must have
      a thorough understanding of the structure and function of the instrument. This is
      the second in a series of articles presenting an in-depth look at the care and
      handling of the flexible endoscope. The first article discussed the air and water
      system. This article will focus specifically on the suction and biopsy channel
      system. The flexible endoscope is constructed of several systems that operate
      simultaneously to produce a highly technical, yet effective diagnostic and
      therapeutic medical device. These systems include the air and water system, the
      suction or operating channel system, the mechanical system, the endoscopic
      retrograde cholangiopancreatography (ERCP) elevator system, the optical system,
      and the electrical system. A review of the internal and external structure of the
      flexible endoscope and the functions of the channel system, including infection
      control issues, potential problems and evaluation, and prevention of minor
      problems to avoid expensive repairs, will be addressed.

PMID- 11847861
TI  - Does the "C" in hepatitis C stand for complex?
AB  - Hepatitis C is a disease usually found in asymptomatic adults. After diagnosis,
      these patients are instructed to start a therapy that encompasses oral
      medications and injections three times a week, involving a significant financial
      cost. Patients undergoing this therapy frequently experience unpleasant side
      effects. Unfortunately there is no assurance the virus will respond to therapy.
      The sustained response rate is about 50% for this combination therapy. Why would
      a person who has no outward sign of illness want to go through this treatment?
      This article provides an overview of what is currently known about hepatitis C,
      treatment, and the frequent side effects associated with therapy.

PMID- 11847862
TI  - Does a physically active lifestyle improve symptoms in women with irritable bowel
      syndrome?
AB  - It has been proposed that physical activity moderates physiological or
      psychological responses to chronic conditions. The purpose of this study was to
      determine if women with a chronic functional gastrointestinal (GI) disorder,
      irritable bowel syndrome, had less active lifestyles than healthy controls and to
      test whether active women with irritable bowel syndrome had less severe recalled
      or daily reports of GI, psychological, and somatic symptoms than inactive women
      with irritable bowel syndrome. Questionnaires were used to measure GI and
      psychological distress and somatic symptoms in 89 women who participated in this
      study. A daily symptom and activity diary was kept for one menstrual cycle. Women
      with irritable bowel syndrome were significantly less likely to be active (48%)
      than control women (71%) (X2 = 3.4, p = .05). Within the irritable bowel syndrome
      group, active women were less likely to report a feeling of incomplete evacuation
      following a bowel movement than inactive women (p < .04), yet active women did
      not have less severe recalled psychological or somatic symptoms than inactive
      women. Active women with irritable bowel syndrome reported less severe daily
      somatic symptoms, which were accounted for by a lower level of fatigue (p =
      .003), but not daily GI or psychological symptoms. These results suggest that
      physical activity may produce select symptom improvement in women with irritable
      bowel syndrome.

PMID- 11847863
TI  - PEGs and ethics.
AB  - The ethics of dealing with the provision of nutritional therapies has been
      complicated by technological advances that have affected all of medical science.
      As a result, nurses are increasingly confronted with decisions regarding the
      provision of invasive treatments. Indeed, enormous faith is invested in the
      ability and wisdom of healthcare professionals to alleviate suffering and
      accomplish cure through the application of invasive therapeutic interventions
      such as percutaneous endoscopic gastrostomy (PEG) placement. Such decisions are
      often complex, present a moral dilemma, and are further complicated by prevailing
      politico-economic, social, and cultural influences. The insertion of tubes for
      artificial nutritional support in those patients who can be defined as
      "vulnerable" is no exception. This article explores both the clinical and ethical
      realities of PEG tube placement and use thereafter in vulnerable patients. The
      ethical principles of autonomy, beneficence, and justice are discussed within the
      context of PEG placement and feeding and recommendations are given for nurses
      practicing in the area of gastroenterology.

PMID- 11847864
TI  - Radiation safety in the endoscopy setting.

PMID- 11847865
TI  - Reuse of single-use critical medical devices.

PMID- 11847866
TI  - Adverse reactions related to phenergan.

PMID- 11847867
TI  - Needlestick protection.

PMID- 11847868
TI  - Reuse of single-use critical medical devices.

PMID- 11847869
TI  - Self-reported benefits of t'ai chi practice by older women.
AB  - Self-rated health is a powerful and consistent predictor of self-care capability
      and health outcomes including mobility, morbidity, and mortality. Exercise is
      important for health and functioning of older adults. Although daily physical
      activity is advocated for reducing many health risks and maintaining mobility,
      older women are generally not heeding the message. Exercise interventions for
      older women should be age appropriate. T'ai chi, an ancient Chinese martial art,
      involves an integration of the mind and body in slow, circular movements and
      changes in the center of gravity. Although there is a growing body of literature
      on the health benefits of t'ai chi exercises, few studies focus on the self
      assessment of health benefits of t'ai chi for older women. This within
      participants, single-factor study of women aged 72 to 96 years resulted in
      statistically significant improvement in self-assessed health as well as numerous
      self-reported benefits after 3 months of t'ai chi exercise participation.

PMID- 11847870
TI  - Facilitators and barriers to elders' practice of t'ai chi. A mind-body, low
      intensity exercise.
AB  - Research has documented the positive effects that t'ai chi has on the well-being
      of elders. However, the reasons that elders practice t'ai chi have not been
      explored. The purpose of this study was to describe the facilitators and barriers
      to t'ai chi practice in elderly populations. Taiwanese community-dwelling elders
      (40 of whom practiced t'ai chi and 40 who did not) aged 65 and older, matched on
      age and gender, were interviewed. Results showed that encouragement from others
      was the most important factor for elders to practice t'ai chi, whereas positive
      health outcomes were the reason they continued to practice it. Most of the non
      t'ai chi group participants had never thought about practicing t'ai chi because
      they felt they were too weak to practice. Because t'ai chi can be helpful in
      promoting the well-being of elders, it is essential for health care professionals
      to overcome the barriers to its uses in elderly populations.

PMID- 11847871
TI  - The use of human touch to improve the well-being of older adults. A holistic
      nursing intervention.
AB  - Touch and massage are viable nursing modalities that are both underutilized and
      understudied. This underuse of touch is especially noted in settings aimed at
      improving the well-being of older adults. A number of studies suggest that the
      appropriate use of touch by nurses has the potential to significantly improve the
      health status of older adults. In particular, touch can be useful with
      cognitively impaired, institutionalized, or hospitalized older adults. Likewise,
      touch can be useful for improving comfort and communication among terminally ill
      older adults and their loved ones. This article synthesizes some of the available
      literature on the subject while suggesting avenues for nursing practice and
      education aimed at using touch as a viable and cost-effective holistic
      gerontological nursing intervention.

PMID- 11847873
TI  - An explication of nursing and family caring for older adults.
AB  - The purpose of this article is to present a holistic approach to the care of
      older adults by family members who are steadily assuming more responsibility for
      their care. Nurses can greatly enhance this care through the establishment of
      collaborative partnerships with family caregivers. Nursing and family caring as
      collaborative partnerships build on Harvath et al.'s work on establishing
      partnerships with family caregivers and Bowers' theory of intergenerational
      caregiving. Through the use of nursing and family caring as collaborative
      partnerships, nurses can empower family members to promote the health of older
      adults.

PMID- 11847872
TI  - A not-so-silent cry for help. Older female cancer caregivers' need for
      information.
AB  - Cancer family caregivers face uncertainty every day. The holistic health care
      practitioner is in a unique position to alleviate some of this uncertainty by
      providing information. Although this may appear to be straightforward,
      unfortunately, more often than not, information is not provided or is provided in
      such a way that it is more harmful than helpful. This article presents findings
      from a qualitative study conducted with 21 older female caregivers of persons
      with advanced-stage cancer. Six areas of concern or need arose from the data and
      are presented with caregiver narrative examples. This article's purpose is not to
      be prescriptive (e.g., telling holistic health care practitioners what to say and
      how to say it). Instead, the purpose is to highlight the need for holistic health
      care practitioners to evaluate their caregivers' individual needs for information
      and to attempt to provide this information in a sensitive yet factually accurate
      manner.

PMID- 11847874
TI  - Grandparent parents. Intergenerational surrogate parenting.
AB  - There is an increasing prevalence in the United States of intergenerational
      surrogate parenting. In fact, grandmother-headed households that include
      grandchildren without their parents are the fastest growing intergenerational
      surrogate family combination. This article reviews the intergenerational
      surrogate family phenomenon relative to its impact on the grandmothers' health
      and offers resources and implications for nursing.

PMID- 11847875
TI  - [World-wide initiative against chronic obstructive bronchitis. GOLD (Global
      Initiative for Chronic Obstructive Lung Disease) should save lungs].

PMID- 11847876
TI  - [Public health scourge onychomycosis. Partial restoration has of no value at
      all].

PMID- 11847877
TI  - [A dream can become reality. How to walk after paraplegia?].

PMID- 11847878
TI  - [Made to measure hip by medical robots. Surgical assistant of steel (interview by
      Ulrike Zechbauer)].

PMID- 11847879
TI  - [Early detection and follow-up of prostatic carcinoma. Responsibilities of the
      general practitioner].
AB  - Apart from digital rectal examination, the determination of prostate specific
      antigen is essential for the early detection of cancer of the prostate. The
      combination of these two examinations significantly improves screening efficacy.
      With the aid of a well-tested algorithm, the family doctor can establish the need
      for a urological investigation, and thus help to ensure early, curative
      treatment. Preventive measures can be rendered more effective by providing
      individual advice on such matters as lifestyle (risk factors, diet). It now
      appears that dietary measures are capable of slowing the increase in PSA
      following definitive treatment. Schematic disease-specific aftercare is usually
      the domain of the urologist. The general practitioner, however, is confronted by
      such problems as logistical considerations, documentation, palliative management
      (e.g. treatment of pain) and the problems associated with concomitant symptoms,
      the relevance of which needs to be assessed. Overall, however, the main concern
      of the general practitioner is with aspects of rehabilitation.

PMID- 11847880
TI  - [Prostatectomy, brachytherapy, percutaneous irradiation. Which method helps your
      patients the most?].
AB  - For the treatment of cancer of the prostate that has not yet metastasized,
      several therapeutic options that promise lasting local tumour control are now
      available: Among the surgical options, radical retropubic prostatectomy is most
      commonly employed. The basic radiotherapeutic options are interstitial and
      external beam irradiation, or a combination of the two. The choice of the most
      suitable therapeutic approach is determined by the extent of the tumor, and the
      side effects that are acceptable to the patient.

PMID- 11847881
TI  - [CT and nuclear magnetic resonance conquer the diagnostic terrain. End of the
      heart catheter?].

PMID- 11847882
TI  - [Prostate cancer--what now? How a self-help group helps coping with the illness].

PMID- 11847885
TI  - [25th Scientific Annual Meeting. Antihypertensive therapy could use improvement].

PMID- 11847884
TI  - [Therapy relevant differences in beta blockers and ACE inhibitors. Innovation or
      plagiarism?].
AB  - As exemplified by the two classes of substance beta blockers and ACE inhibitors,
      the question is considered as to when new developments within a drug family can
      be termed innovations and when they must be seen purely as plagiarisms ("me-too"
      preparations). It is noted that in principle no innovations are to be expected
      from generics, since these substances are are not the subject of specific
      research. Although large-scale clinical studies in recent years have identified a
      new indication--cardiac insufficiency--for the beta blockers metoprolol,
      bisoprolol and carvedilol, this must not be considered an innovation in the sense
      of a new development. The translatability of the study results to uninvestigated
      substances is uncertain. In contrast to the beta blockers, the indications for
      the ACE inhibitors have long been known, but again, the new generic preparations
      that have come onto the market are not innovations.

PMID- 11847883
TI  - [Suggestions for the common cold season. Managing cough, rhinitis and earaches].

PMID- 11847886
TI  - [New governing body of the German Hypertension League].

PMID- 11847887
TI  - [Endothelial dysfunction moves into focus].

PMID- 11847888
TI  - [Borderline hyperthyroidism. When must it be treated?].

PMID- 11847889
TI  - [Physical endurance improves markedly. New therapy approach in pulmonary
      hypertension].

PMID- 11847890
TI  - [Intima-media thickness in hypertensive patients. Calcium blockers controls
      atherosclerosis].

PMID- 11847891
TI  - [Alzheimer dementia. Intervening as early as possible].

PMID- 11847892
TI  - [Hexavalent vaccines facilitate compliance. Vaccination calendars become
      significantly simpler].

PMID- 11847894
TI  - [Chronic decubitus, ulcus cruris. Maggots feed for wound healing].

PMID- 11847893
TI  - [Stress intolerance in diastolic dysfunction. A case for AT1 blocker?].

PMID- 11847895
TI  - Development of effective strategies to support breastfeeding.

PMID- 11847896
TI  - Hydrogel dressings.

PMID- 11847897
TI  - Hydrogel dressing for treatment of sore nipples during early lactation: should we
      be promoting these products?

PMID- 11847898
TI  - Breastfeeding knowledge and beliefs among adults in eastern Tobago.
AB  - Using a cross-sectional survey, the knowledge and beliefs about breastfeeding
      were evaluated among adults in Eastern Tobago (N = 509). Of the respondents, 95%,
      69%, and 48% indicated that a baby should be exclusively breastfed at birth, 3
      months, and 6 months, respectively. The baby's mother was thought to have the
      greatest influence on breastfeeding decisions. Of the respondents, 63% and 80%
      were unaware of expressed breast milk and cup-feeding a neonate, whereas 82%
      believed that a solely breastfed baby should receive water. Additionally, 23% and
      44% felt that breastfeeding should be terminated before 6 months and between 6
      and 12 months, respectively. Inadequate maternal nutrition and employment were
      reported as the principal factors affecting breastfeeding. There is a lack of
      knowledge about the anatomy and physiology of lactation and about the benefits of
      exclusive breastfeeding. These findings are useful for guiding the development
      and implementation of interventions to promote breast-feeding in Tobago.

PMID- 11847899
TI  - Long-term breastfeeding: nourishment or nurturance?
AB  - Mothers frequently describe the primary benefit of breastfeeding beyond a year as
      providing comfort rather than nourishment. Little is known about the effect of
      extended breastfeeding on the growth or nutritional status of children in the
      United States. Data collected on 38 long-term breastfeeding children (12 to 43
      months old) included growth measurements, breastfeeding patterns, and dietary
      intake obtained through diaries and dietary recalls. Although the children's
      weight-for-age, length/height-for-age, and weight-for-length/height Z scores
      clustered below zero, they fell within two standard deviations of the median,
      suggesting normal growth. The daily time and frequency of breastfeeding were not
      different between the 1-year-old and 2-year-old age groups but were significantly
      lower in the 3-year-old age group. In an analysis of non-breast milk diets, the
      children would need an average intake of 100 to 460 mL of breast milk per day to
      meet the RDA for energy intake and nutrients that were lower in their diets
      compared to national food intake surveys.

PMID- 11847900
TI  - Exclusive breastfeeding in the era of AIDS.
AB  - The aim of this study was to describe breastfeeding practices, as well as what
      pregnant women know about breastfeeding and mother-to-child transmission (MTCT)
      of HIV, and explore factors associated with exclusive breastfeeding, especially
      in the presence of HIV/AIDS. A cross-sectional interview survey of 500 pregnant
      women was conducted in the Kilimanjaro region, supplemented by focus group
      discussions with pregnant women. Among the 309 mothers having previously
      breastfed, 85% had initiated breastfeeding within the first few hours postpartum,
      and 18% of newborns received some prelacteal food. Mean duration of breast
      feeding was 23.7 months, but 46% of mothers had introduced other fluids early.
      Knowledge of HIV-transmission through breastfeeding was not associated with
      breastfeeding practices. Married women (odds ratio [OR] = .09, 95% confidence
      interval [CI] = .04-.24) and those having knowledge of exclusive breastfeeding
      (OR = .08, 95% CI = .02-.31) were the least likely to end exclusive breastfeeding
      early. Exclusive breastfeeding is a rare practice, and MTCT of HIV may further
      complicate recommendations with regard to this practice.

PMID- 11847901
TI  - Factors associated with exclusive breastfeeding in Ibadan, Nigeria.
AB  - Although nationwide efforts to promote exclusive breastfeeding began in Nigeria
      in 1992, data on this type of infant feeding are still generally scarce. Current
      status breastfeeding data were obtained from 2794 mothers, enrolled from randomly
      selected infant welfare clinics in Ibadan, Nigeria, to evaluate factors that are
      associated with exclusive breastfeeding. The exclusive breastfeeding rate dropped
      from 57.4% at 1 month to 23.4% at 6 months. Using multiple regression analysis,
      younger age of infant (P < .0001), higher maternal occupation (P < .05), and
      delivery in tertiary (P < .0001) or secondary (P < .0001) health facility were
      predictive of exclusive breastfeeding. Mothers 24 years or younger and
      primiparous mothers were less likely to breastfeed their babies exclusively (P <
      .01 and P < .05, respectively). Additional programs are needed to meet the needs
      of at-risk mothers, who should be identified and counseled.

PMID- 11847902
TI  - Extending breastfeeding duration through primary care: a systematic review of
      prenatal and postnatal interventions.
AB  - This literature review provides an overview of the effectiveness of strategies
      and procedures used to extend breastfeeding duration. Interventions carried out
      during pregnancy and/or infant care conducted in primary health care services,
      community settings, or hospital clinics were included. Interventions covering
      only the delivery period were excluded. Interventions that were most effective in
      extending the duration of breastfeeding generally combined information, guidance,
      and support and were long term and intensive. During prenatal care, group
      education was the only effective strategy reported. Home visits used to identify
      mothers' concerns with breastfeeding, assist with problem solving, and involve
      family members in breastfeeding support were effective during the postnatal
      period or both periods. Individual education sessions were also effective in
      these periods, as was the combination of 2 or 3 of these strategies in
      interventions involving both periods. Strategies that had no effect were
      characterized by no face-to-face interaction, practices contradicting messages,
      or small-scale interventions.

PMID- 11847904
TI  - Evidence-based nursing: 4 years down the road.

PMID- 11847903
TI  - Antipsychotics and breastfeeding.
AB  - Nearly 10% of all postpartum women will experience some form of psychiatric
      illness. The development of postpartum psychosis consisting of symptoms such as
      auditory hallucinations, delusions, and disorganization is greatest within the
      first 4 weeks after delivery. In fact, a majority of cases (54%) occur within 14
      days of delivery. Due to a more favorable side-effect profile, atypical
      antipsychotics are generally preferred over traditional antipsychotics for the
      treatment of psychotic symptoms. Unfortunately, there are minimal guidelines
      established with regard to the use of antipsychotics during lactation. This
      article will review currently available data on the excretion of traditional and
      atypical antipsychotics into breast milk and make recommendations with regard to
      the use of individual agents during lactation.

PMID- 11847905
TI  - Review of adverse events reported following use of yellow fever vaccine--Canada,
      1987-2000.

PMID- 11847906
TI  - The CRASH trial--the first large-scale randomised controlled trial in head
      injury.

PMID- 11847907
TI  - Effects of the changing political dispensation in South Africa on growth of urban
      secondary schoolchildren.

PMID- 11847908
TI  - Attitudes to disclosure of HIV status to sexual partners.

PMID- 11847911
TI  - Guarding the citadels of AIDS stats.

PMID- 11847909
TI  - Hyperbaric oxygen therapy for children with cerebral palsy.

PMID- 11847910
TI  - Health horror in packed Pollsmoor.

PMID- 11847912
TI  - Progress towards developing a vaccine to prevent HIV and AIDs in South Africa.

PMID- 11847913
TI  - Cushing's syndrome caused by ectopic ACTH secretion from pulmonary tumourlets.

PMID- 11847915
TI  - 'Pathology'--two separate disciplines.

PMID- 11847914
TI  - Ethical issues in continuing professional development.

PMID- 11847916
TI  - Systemic candidiasis--some facts.

PMID- 11847917
TI  - Sentinel malaria surveillance--more than a research tool.

PMID- 11847918
TI  - Failure of sulphadoxine-pyrimethamine in treating Plasmodium falciparum malaria
      in KwaZulu-Natal.

PMID- 11847919
TI  - Aetiology of lower airway infections in hospitalised children under 18 months of
      age in the Bloemfontein area.

PMID- 11847920
TI  - Therapeutic efficacy of sulfadoxine-pyrimethamine in uncomplicated Plasmodium
      falciparum malaria 3 years after introduction in Mpumalanga.
AB  - OBJECTIVES: To assess therapeutic efficacy of sulfadoxine-pyrimethamine (SP) in
      treatment of uncomplicated Plasmodium falciparum malaria 3 years after
      introduction in Mpumalanga, South Africa. SETTING: Tonga district with a
      population of 116,418 and subject to seasonal malaria, with an average annual
      incidence of 3,200 cases. SUBJECTS: One hundred and nineteen malaria patients
      presenting to a sentinel surveillance clinic and recruited according to World
      Health Organisation (WHO) criteria. METHODOLOGY: Patients satisfying WHO
      inclusion criteria were treated with a single oral dose of SP and the response of
      infection to treatment in each patient was routinely monitored clinically and
      parasitologically on days 1, 2, 3, 7, 14, 21, 28 and 42 post-treatment. One
      hundred and ten patients completed follow-up to day 42 or evidence of clinical or
      parasitological failure. RESULTS: The cure rate at day 42 was 93.6% (103/110).
      Two patients (1.8%, RII) were early treatment failures on day 3, while
      recrudescence (4.5%, RI) occurred in 5 patients on day 28 (N = 3) and on day 42
      (N = 2). CONCLUSION: In Mpumalanga P. falciparum remains sensitive to SP, with no
      significant difference between the baseline cure rate (94.5%) and the cure rate
      in the present study (93.6%).

PMID- 11847921
TI  - Malaria control--two years' use of insecticide-treated bednets compared with
      insecticide house spraying in KwaZulu-Natal.
AB  - OBJECTIVES: The objective of this study was to produce data indicating whether
      insecticide-treated bednets should replace insecticide house spraying as a
      malaria control method in South Africa. We report 2 years of preliminary data on
      malaria incidence comparing areas receiving insecticide-treated bednets and those
      subjected to house spraying in northern KwaZulu-Natal. DESIGN, SETTING AND
      SUBJECTS: In order to measure significant reductions in malaria incidence between
      the two interventions, a geographical information system (GIS) was used to
      identify and create seven pairs of geographical blocks (areas) in the malaria
      high-risk areas of Ndumu and Makanis in Ingwavuma magisterial district, KwaZulu
      Natal. Individual blocks were then randomly allocated to either insecticide
      treated bednets or house spraying with deltamethrin. Malaria cases were either
      routinely recorded by surveillance agents at home or were reported to the nearest
      health facility. RESULTS AND CONCLUSIONS: The results show that 2 years' use of
      insecticide-treated bednets by communities in Ndumu and Makanis, KwaZulu-Natal,
      significantly reduced the malaria incidence both in 1997 (rate ratio (RR) =
      0.879, 95% confidence interval (CI) 0.80-0.95, P = 0.04) and in 1998 (RR = 0.667,
      CI 0.61-0.72, P = 0.0001). Using a t-test, these significant reductions were
      further confirmed by an assessment of the rate of change between 1996 and 1998,
      showing a 16% reduction in malaria incidence in blocks using treated bednets and
      an increase of 45% in sprayed areas (t = 2.534, P = 0.026 (12 df)). In order to
      decide whether bednets should replace house spraying in South Africa, we need
      more data on the efficacy of treated bednets, their long-term acceptability and
      the cost of the two interventions.

PMID- 11847922
TI  - The increasing burden of tuberculosis in pregnant women, newborns and infants
      under 6 months of age in Durban, KwaZulu-Natal.
AB  - OBJECTIVES: In spite of the global epidemic of tuberculosis (TB) which has been
      exacerbated by HIV, the impact of these co-infections on maternal and perinatal
      health has been limited. We document new evidence from Durban, KwaZulu-Natal, on
      the increasing effects of TB in pregnant women, neonates and infants. METHOD:
      Women with TB were prospectively studied at the antenatal clinics and obstetric
      and labour wards at King Edward VIII Hospital, Durban, between 1996 and 1998. The
      incidence of TB was calculated, and the population-attributable fraction of TB
      due to HIV infection in pregnancy was estimated. Concurrently, culture-confirmed
      cases of Mycobacterium tuberculosis in neonates and infants under 6 months of age
      at the hospital were documented. RESULTS: One hundred and forty-six cases of
      maternal TB were detected. TB occurred in 0.1% and 0.6% of maternities in 1996
      and 1998 respectively. Overall, TB rates for HIV non-infected maternities was
      72.9/10(5), and for HIV-infected maternities, 774.5/10(5). The attributable
      fraction of TB related to HIV in pregnancy was 71.7%; 10.3% of these mothers
      died. There was a 2.2-fold increase in the caseload of culture-confirmed TB in
      neonates and young infants at the hospital. CONCLUSION: In regions where TB and
      HIV prevalence is high, efforts to improve maternal and perinatal health must
      include the detection of TB in pregnancy.

PMID- 11847923
TI  - Microvascular complications in South African patients with long-duration diabetes
      mellitus.
AB  - OBJECTIVE: To determine the prevalence of microvascular complications in South
      African black and Indian patients with long-duration diabetes mellitus (DM).
      DESIGN: A retrospective analysis was undertaken of clinical records of 219 DM
      patients (132 black, 87 Indian) with long-duration DM (over 10 years) attending a
      diabetes clinic in Durban. Data recorded on each subject included demographic
      details (age, gender, ethnic group, type of diabetes, age of onset and duration
      of diabetes), presence of retinopathy, markers of nephropathy and biochemical
      variables. The prevalence of complications and the clinical and biochemical
      parameters were evaluated for type 1 and type 2 diabetes and for each ethnic
      group. RESULTS: Of the 219 patients, 47 had type 1 DM (36 blacks, 11 Indians) and
      172 were classified as type 2 DM (96 blacks, 76 Indians). The mean age of onset
      of DM was later in blacks than Indians, both for type 1 (P < 0.05) and type 2 DM
      (P < 0.01). In patients with type 1 DM, the prevalence of retinopathy was 53.2%
      (blacks 55.6%, Indians 45.5%), persistent proteinuria was found in 23.4% (blacks
      25%, Indians 18.2%) and hypertension in 34%. No ethnic difference was found
      except for the prevalence of hypertension which was higher in blacks than Indians
      (41.7% v. 9.1%, P < 0.5). Onset of retinopathy from time of diabetes diagnosis
      occurred earlier in blacks than Indians (13.0 +/- 4.6 yrs v. 18.0 +/- 4.6 yrs, P
      < 0.05). For the type 2 DM group, retinopathy was found in 64.5% (black v. Indian
      68.8 v. 59.2%) and persistent proteinuria in 25% (black v. Indian 30.2 v. 18.4%).
      Hypertension was observed in 68% and was more prevalent in blacks (84.4 v. 47.4%,
      P < 0.01) There was an earlier onset of retinopathy (P < 0.05) and hypertension
      (P < 0.01) from time of diabetes diagnosis in blacks than Indians. In the type 1
      DM group retinopathy was associated with a significantly longer duration of
      diabetes (P < 0.05) and higher glycated haemoglobin (HbA1) (P < 0.05). For type 2
      DM subjects there was a significant association between retinopathy and longer
      duration of diabetes (P < 0.05) and higher systolic blood pressure (P < 0.05).
      CONCLUSION: This study has shown that there is a high prevalence of microvascular
      complications in South African patients with long-duration diabetes mellitus.

PMID- 11847924
TI  - An assessment of growth in high and low socio-economic status schoolchildren in
      South Africa.

PMID- 11847925
TI  - Factors influencing peak expiratory flow in teenage boys.
AB  - BACKGROUND: Peak expiratory flow (PEF) is a useful measure of pulmonary health
      status and is frequently utilised in asthma management. Reduction in PEF is
      usually indicative of onset of asthma symptoms. However, use can be made of PEF
      values only if normal values are known. The definition of normal range is always
      difficult and may vary between regions and be affected by a variety of factors.
      OBJECTIVE: To establish PEF values for teenage boys in a Cape Town suburb and
      examine factors that possibly influence this measurement. SETTING: A high school
      for boys in the southern suburbs of Cape Town. METHODS: Measurements of PEF were
      taken for 124 boys. Subjects were approximately 16 years old and apparently
      healthy at the time of survey. Further details were provided by means of a
      questionnaire. RESULTS: PEF ranged from 350 to 760 l/min, with a mean (+/-
      standard deviation (SD)) of 539 +/- 68 l/min. Factors expected to influence PEF
      included height and mass, whereas unexpected factors included sport intensity and
      academic grade. A trend to reduced peak flow was already evident in boys who
      smoked and boys from homes where a parent smoked. Regression analysis suggested
      peak flow differences in our population compared with the standard reference.
      CONCLUSION: Interpretation of results obtained from peak-flow instruments should
      take into account additional knowledge concerning the individual. Further surveys
      of the South African population and of different groups should be done to
      establish local standards and factors influencing PEF.

PMID- 11847926
TI  - [Unreamed locking intramedullary nailing of humeral fractures--basic evaluation
      of a patient group].
AB  - PURPOSE OF THE STUDY: The aim of the work is to provide an overview of the
      existing experience in Synthes unreamed humeral nail (UHN). MATERIAL: Between
      August 1996 and February 2000 we treated by means of UHN a group of 37 patients
      (12 men and 25 women), average age 55 years (range, 18-87 years) with a fracture
      of humeral shaft. According to AO classification in 10 patients it was a case of
      a fracture of proximal humerus involving the shaft (11B-3) and in 27 cases a
      fracture of the shaft (12 A, B, C). The whole group was operated on by 11
      surgeons. METHOD: In 26 cases we used the antegrade method and in 11 cases the
      retrograde one, in dependence on the type and location of the fracture. The
      assessment was performed in the form of a prospective study. The follow-up
      including radiograph checks was carried out at the intervals of 6 weeks, 3, 6, 9
      and 12 months after the operation or at another 6 weeks or 3 months after the
      extraction of the nail, if any. In addition we invited the whole group, i.e. 37
      patients for the final control examination which all of them attended. This
      examination was performed by the first author of the work. The average follow-up
      was 38 months (range, 12-55 months). RESULTS: The average duration of the surgery
      in the whole group was 80 minutes, the average duration of x-ray exposure was 3.1
      minutes. Peroperative complications occurred in total 42 times in 23 patients.
      Seven cases required a supplementary incision, i.e. open reduction of the
      fracture; insufficient nail placement (not into the proper depth) in the humeral
      head and its prominence into joint line evaluated on the post-operative
      radiograph) in antegrade nailing occurred 6 times. Problems with locking were
      encountered 15 times in 10 patients. Comminution of the fragments peroperatively
      during the insertion of the nail occurred 3 times, peroperative injury of the
      radial nerve was recorded in total 4 times, always in the antegrade method of the
      insertion during distal locking from the lateral side. A postoperative
      complication occurred 16 times in 12 patients, 6 times the radiograph showed
      penetration of the end of the nail into the shoulder and 6 times the locking
      screws loosened. No infect was recorded. The mentioned complications required in
      total 10 revision surgeries in 6 patients (5 of them were treated by the
      antegrade method). The fracture healed in a good anatomical position in 33 cases.
      In 4 cases there occurred non-union which was 3 times treated with a plate re
      fixation and cancellous bone grafting of which twice successfully. In 2 cases the
      healing required another revision surgery. A good subjective as well as objective
      result was achieved almost in 90% of patients. A risk factor from the viewpoint
      of the limitation of the range of motion in the shoulder proved to be the
      fracture of 11B3 type and also the antegrade method of nailing, in case of the
      elbow the retrograde method of nailing. However, the greatest risk was posed by
      the necessity of a longer post-operative immobilisation of the limb in the case
      of a not quite stable internal fixation. DISCUSSION: A relatively high number of
      complications in our group results from strict criteria we have set. However,
      also literary data present a relatively high number of variously serious
      complications. Our results as well as the average duration of the surgery is
      comparable with other authors. CONCLUSION: The main indication of UHN are
      comminuted or multi-level fractures of humerus in the central three fifths of its
      length. If possible we prefer the retrograde method of nailing, in the antegrade
      method we recommend distal locking from the anterior aspect of the arm.
      Transverse or short oblique fractures can be successfully treated by a simpler
      Hackethal technique. Long spiral fractures are ideally treated conservatively or
      by plate fixation.

PMID- 11847928
TI  - [Repair of chondral defects of the knee using a combination of autologous
      chondrocytes and osteochondral allograft--an animal model. Part I: in vitro
      culture of autologous chondrocytes].
AB  - PURPOSE OF THE STUDY: In the study we used in vitro cultivated autologous
      chondrocytes in combination with osteochondral allografts for the treatment of
      local defects of articular cartilage on the animal model (rabbit). MATERIAL:
      Chondrocytes for in vitro cultivation were harvested by biopsy of articular
      cartilage of rabbit. For the monolayer cultivation we used Nutrient mix F 12
      (Gibco BRL) with addition of Lascorbic acid (50 micrograms/ml, Sigma) and insulin
      trasferin-selenium (A 6.26 micrograms/ml, Gibco BRL), 20% of fectal serum (Gibco
      BRL) and antibiotic antimycotic solution (Gibco BRL). Cultivation of chondrocytes
      took place at 37 degrees in the atmosphere of 5% CO2. Multiplied chondrocytes re
      suspended in fibrin glue in combination with two osteochondral allografts were
      used for the reparation of artificial defect of the rabbit cartilage. METHODS:
      For the analysis of collagen type II in the cultivation medium we used the
      principle of salting out by 30% ammonium sulphate and subsequent pepsinization in
      an acid environment with a repeated salting out by means of 2M of NaCl.
      Precipitates were dissolved in 5.0 M of acetic acid and used for SDS PAGE and
      immunoblotting. As a detection system we used ECL (Amersham/Pharmacia Biotech).
      RESULTS: The final average number of chondrocytes multiplied by monolayer
      cultivation was 1.10(5). The presence of collagen of type II has proved the
      preservation of the original phenotype of chondrocytes during cultivation.
      DISCUSSION: Bioengineering use of cell and tissue cultivation provides new
      options of the treatment of defect of connective tissue. Transplantation of
      autologous chondrocytes in combination with osteochondral allografts is on the
      basis of our results obtained so far a promising therapy. CONCLUSION: The aim of
      our work was an ex vivo expansion of autologous chondrocytes for the purpose of
      cell transplantation.

PMID- 11847927
TI  - [Rotational acetabular osteotomy in the treatment of Legg-Calve-Perthes disease].
AB  - PURPOSE OF THE STUDY: The material of prospective study involving 57 surgically
      treated hips in 55 patients suffering with a severe form of Legg-Calve-Perthes
      disease (LCPD) was analysed by the use of statistical methods to depict the
      influence of age, of sex, of the amount of head involvement on the outcomes of
      surgical treatment by rotational acetabular osteotomy (Salter or Steel osteotomy
      from 9 years of age). MATERIAL: During the period 1990-2000 rotational acetabular
      osteotomy for Legg-Calve-Perthes disease was performed totally in 124 patients.
      Excluded were cases, in which the operation was done for residual subluxation as
      a definitive outcome of former LCPD, cases which did not return for controls,
      cases with not yet completed consolidation after surgery and cases operated by me
      abroad. Totally were analysed stastistical sheets from 57 rotational acetabular
      osteotomies, including basis dates from medical history, clinical and x-ray
      examinations. Special concern was given to the evaluation of remodellation of the
      affected femoral head chronologically. METHODS: All patients were operated by the
      group of three senior orthopaedic surgeons. Indication for surgery was based on
      the evidence of the progressive collapse of the femoral head issuing in the
      lateral and anterior head extrusion. As the Mose as well as Stulberg
      classification are showing inter-rater discrepancies, authors measured as well
      head-neck index, epiphyseal index and acetabulum-head index to eliminate
      subjectives errors. RESULTS: Age at operation and sex did not affect the results
      expressed in epiphyseal quotient and acetabulum-head index. With the increasing
      age the head-neck index dropped down depicting the progressive shortening of the
      femoral neck the older kids. The periods from the operation till the
      consolidation of the lateral pillar of the femoral head were longer in younger
      than in older children. Although the evaluation of results in Mose classification
      showed poorer results generally and also specifically in relation to the
      increasing age, distribution of results in Stulberg classification showed
      excellent and fair results in almost 90% of all treated patients. DISCUSSION:
      Prospective study based on the use of rotational osteotomy, avoiding the routine
      combination with varisation of the proximal femur in older kids using in them
      Steel triple osteotomy, showed promising results especially in Stulberg
      classification. Contrary to Salter and others prerequisiting for the indication
      of operation only slight deformity of the affected femoral head, many of the
      enrolled cases appeared with the remarkable deformity of the femoral head before
      the operation. Rotational acetabular osteotomy showed its potential to involve
      the enlarged head and follow-up depicted its subsequent slow remodellation.
      CONCLUSIONS: Submitted study was prepared to be matched nextly with the
      conservative group, which will be published in another publication. Internal
      analysis of the presented cohort disclosed that presented surgical treatment
      (Salter or Steel osteotomy respectively) assured, that irrespective of higher
      age, the important parameters like epiphyseal quotient and acetabulum-head index
      did not become worse than in younger groups. Even in the group over 9 years of
      age, 87.5% were categorised like excellent and fair results in Stulberg
      classification.

PMID- 11847929
TI  - [Verification of a surgical technique using a new biotitanium cage in
      degenerative diseases of the lumbar spine--experimental study].
AB  - PURPOSE OF THE STUDY: Authors performed experimental PLIF operations on cadavers
      to verify appropriate shape and size of cage made from bioactive titan material.
      The approach for application into intervertebral space of the lumbar spine and
      appearance on X-ray and CT scans was also investigated. MATERIAL: In experiment
      on cadavers five implantations of interbody cages were performed, two of them in
      interbody space L3/L4 and three of them in L4/L5. Subtotal discectomy and end
      platec preparation was done before cage insertion. Our type of cage is made from
      bioactive titan material and fastened in the application instrument that we
      developed for this purpose. METHOD: To verify operational approach we used
      midline incision and opened spinal canal through laminectomy, partial
      hemilaminectomy or partial medial facetectomy. This phase was followed by
      discectomy and end plates preparation. Stability of inserted cages in
      intervertebral space is ensured by rotation and anchorage of cage wings in end
      plates. Operated motion segment was taken out and evaluated by X-rays and CT
      scans. RESULTS: The operational approach through partial hemilaminectomy and
      partial medial facetectomy was fully sufficient for cage application with respect
      to operated segment. All implantations were successful and position of cages
      satisfactory. Thanks to less robust gripping instrument the approach was more
      thrifty compared to glass-ceramic cage and comparable with commercially produced
      cages that we have experience with (Spine Tech, Stryker, Comesa). Due to cage
      radio opaque, proper position of cages is easy to control on X-ray and CT scans
      and allows good peroperative monitoring by X-ray magnifier. DISCUSSION: Usage of
      bioactive materials in spinal surgery started by introduction of glass ceramics.
      Based on our experience we determined suitable indications. To eliminate some of
      te disadvantages of glass ceramics (mainly mechanical properties), a cage made
      from bioactive material was developed. This type of cage does not require bone
      harvesting to fill the cage. This fact results in better comfort for patient in
      postoperative period and eliminates complications from bone graft harvesting.
      Bioactive surface of the cage with osseo conductive and osseo integrative
      features creates prerequisites for solid fusion without bone grafts. Titanium
      material guarantees mechanical strength and makes possible to produce a wide
      range of shapes and sizes. Strength of the material enables more advantageous
      gripping of cage in application instrument. The cage is well visible on X-ray and
      in MRI scans artifacts are considerably reduced. Operational approach and
      technique are similar to other commercially produced cages and the extent of
      destabilization is limited to minimum. CONCLUSION: Experimentally we repeatedly
      verified operational approach, suitable shape and applicability of bioactive
      titanium cage into intervertebral space. For clinical use bioactive titanium
      could be a possible way how to replace bone grafts. For spinal surgeons it
      represents a chemically and mechanically stable material capable of interaction
      in an environment where it is implanted. Even in difficult conditions the level
      of osseo integration is high.

PMID- 11847930
TI  - [Indications for emergency surgery in thoraco-abdominal injuries].
AB  - PURPOSE OF THE STUDY: Under the conditions of an increasing number of car
      accidents and criminal injuries the thoracis and abdominal trauma is a source of
      a significant morbidity and mortality in blunt and penetrating mechanism of
      injury. On the basis of a group of patients operated on for blunt and penetrating
      injury of the chest and abdomen evaluation was made of the current indication and
      results of lifesaving surgery in case of these injuries. PATIENTS: The group
      included 68 patients requiring a lifesaving surgery for a blunt and penetrating
      injury of the chest and abdomen hospitalized between the beginning of 1966 and
      the end of April 2001. Forty-five patients sustained a blunt injury and 23 a
      penetrating injury. METHODS: In case of blunt injuries the indication for surgery
      was determined on the basis of clinical examination supplemented with a
      radiograph examination of the chest and spiral computer tomography. In case of
      penetrating stab wounds the surgery was indicated on the basis of clinical
      examination, in gunshot wounds by means of x-ray examination and spiral computer
      tomography performed in order to assess the scope of the injury of intraabdominal
      organs and the location of the projectile. Indicated on the basis of the
      examination in the blunt injury was thoracotomy in 6 cases, laporatomy in 34
      cases and the combination of thoracotomy and laparotomy in 5 patients. In case of
      the penetrating injury thoracotomy was performed in 8 cases, laparotomy in 11
      cases and the combination of thoracotomy and laparotomy in 4 patients. RESULTS:
      In the post-operative period 6 patients (9%) died: 3 patients with a polytrauma
      died from an irreversible damage caused by a protracted hemorrghagic shock, one
      female patient from the contusion of brain, one patient after splenectomy for an
      isolated injury died from cardiorespiratory failure and pneumonia, one patient
      with a stab wound of the left ventricle of the heart died from the heart failure
      by hypoxy. DISCUSSION: Indication for a lifesaving thoracotomy and laparotomy in
      our group of patients operated on corresponds to the overviews of surgeries in
      thoracoabdominal injuries presented in literature. The procedure in preoperative
      examination is identically limited by the stability of hemodynamics in the
      patient after the injury using mainly ultrasound and computer tomography of the
      stabilized patient. In contrast to a number of authors in our conditions we have
      not performed some of the intervention examinations such as diagnostic peritoneal
      lavage or thoracoscopy and laparoscopy. The improvement of results in patients
      operated on for thoracoabdominal injury is in our conditions given both by the
      timeliness of the operation in the availability of examination methods (US,
      spiral CT) and by adequate stabilization of the patient in the peroperative
      period at the emergency department. CONCLUSION: Priority indication for a
      lifesaving surgery in thoracoabdominal injuries is significant intraabdominal
      bleeding diagnosed on the basis of the result of the clinical examination in
      hemodynamically unstable patients. In a stabilized patient the lifesaving surgery
      is performed on the basis of the result of visualization methods (spiral computer
      tomography, ultrasound, angiography, endoscopy) revealing apart from significant
      bleeding also severe injuries of intrathoracic and intraabdominal organs.
      Protracted hypovolemic shock with the development of multi-organ failure or the
      occurrence of simultaneous severe associated injuries in polytrauma are the most
      frequent causes of mortality in patients operated on for thoracoabdominal injury.

PMID- 11847931
TI  - [Osteomyelitis of the spine and its surgical treatment--personal experience].
AB  - PURPOSE OF THE STUDY: Evaluation of surgical treatment of osteomyelitis of the
      spine, determination of efficient diagnostic and therapeutic criteria. MATERIAL:
      The examined group comprised in total 27 patients. No selection was made, all
      patients who were operated on and treated at the Department of the authors were
      followed gradually as they were admitted at the Department. METHODS: Evaluation
      was based on the monitoring of the clinical condition of patients including
      laboratory tests. Evaluated was also the achievement of vertebral body fusion
      three months after the surgery. The surgical procedure always contained a radical
      debridement of inflammatory focus, a massive autogenous cancellous bone grafting
      mixed with Gentamycin foam, either separately or in combination with
      instrumentation. Approach to the inflammatory focus was in 9 cases transforaminal
      posterior, in 2 cases transforaminal combined with transversectomy, in 2 cases
      transforaminal combined with laminectomy, in 4 cases transthoracic, in 1 case
      transabdominal, in 7 cases retroperitoneal and once percutaneous technique was
      used. RESULTS: All patients operated on healed without complications. Local pain
      and temperature subsided rapidly (in terms of days). Also objective inflammatory
      criteria returned to normal (in terms of weeks). Seven patients show improved
      neurological status. X-ray examination 3 months after the surgery always shows
      consolidation and ingrowth of cancellous bone grafts without local relapse or
      loss of correction. DISCUSSION: The numbers of patients of the authors' group
      correspond with the numbers of patients presented in literature. There is also
      agreement with other authors that a modern treatment of spinal osteomyelitis
      should include a radical debridement of the focus combined with instrumentation,
      neurological decompression and application of cancellous bone grafts completed by
      local antibiotics. As compared to other authors who present a prevalence of
      abscess the histological examination of our cases shows predominantly
      inflammatory granuloma. CONCLUSION: Radical surgical treatment of spinal
      osteomyelitis including debridement, cancellous bone grafting, internal fixation
      (instrumentation) and decompression together with a general treatment and
      orthotic management seems to be an efficient way of the treatment of this serious
      disease.

PMID- 11847932
TI  - [Osteoarthrosis--a suggested approach for the general physician] ].

PMID- 11847933
TI  - Factors influencing cyclosporine blood concentration-dose ratio.
AB  - OBJECTIVE: To analyze the trough cyclosporine concentration-dose ratio (CDR) and
      its relationship to some commonly available factors such as cyclosporine dosage,
      patient age, grade of obesity, posttransplant days, serum creatinine, serum
      bilirubin, and serum cholesterol by multiple linear regression. METHODS: The
      study was performed on 866 samples from 90 transplant recipients (25 kidney, 25
      heart, 17 bone marrow, 13 liver, 10 simultaneous pancreas-kidney). RESULTS: The
      results show differences between transplants both in cyclosporine CDR variability
      (expressed by the coefficients of variation) and in the capability of those
      factors to explain this variability (expressed by the coefficient of
      determination). Coefficients of variation were 41% for the 866 samples (from 34%
      in heart to 55% in pancreas-kidney transplantation) and 28% for the 90 patients'
      CDR mean values (from 24% in heart to 32% in pancreas-kidney transplantation).
      All factors, except for the grade of obesity, were related to the cyclosporine
      CDR for all transplants as a whole. However, differences in the influence of each
      factor on each transplant were observed. The coefficient of determination based
      on significant factors was R2 = 0.25 for all samples (from 0.18 in pancreas
      kidney to 0.52 in liver transplantation) and R2 = 0.53 for the patients' CDR
      means (from 0.39 in heart to 0.83 in kidney transplantation). CONCLUSIONS: We
      have quantified the cyclosporine CDR, its variability, and its relationship with
      some commonly available factors and found significant differences between
      transplant types. The equations of regression obtained might improve trough
      cyclosporine CDR estimation as a first step in cyclosporine dosage adjustment in
      kidney and liver transplant recipients.

PMID- 11847934
TI  - Warfarin therapy for atrial fibrillation in the elderly.
AB  - OBJECTIVE: To evaluate a clinical practice model that addresses special needs for
      managing anticoagulation in a community-dwelling elderly population with atrial
      fibrillation and high risk of stroke. METHODS: Medical records of 18 patients
      (mean age 82 y) followed by the Geriatric Ambulatory Program over 2 years, with a
      target international normalized ratio (INR) of 2.0-3.0, were reviewed. Risk
      factors for stroke, number and results of INR tests, suspected reasons for
      suboptimal response, and adverse events were analyzed. Patients were defined as
      having cognitive impairment if they had a Folstein Mini-Mental State Exam score <
      or = 26. Functional impairment was defined by > or = 2 disabilities in activities
      of daily living. RESULTS: Eighty-three percent (15/18) had > or = 2 additional
      stroke risk factors. Fifty-one percent (273/541) of INR responses were
      therapeutic. Female gender (p = 0.015) and cognitive (p = 0.019) and functional
      impairment (p = 0.001) were associated with supratherapeutic INR response. All
      patients with cognitive impairment and 85% of those with functional impairment
      received caregiver support for medication administration. There were 4 minor
      bleeding events and no thromboembolic events. The mean number of medications was
      9.3 in those with bleeding versus 6.8 in those without bleeding (p = 0.052).
      CONCLUSIONS: Elderly patients with high stroke risk achieved therapeutic INR
      responses. However, those with significant cognitive or functional impairment
      require caregiver support and special consideration for anticoagulation
      management.

PMID- 11847935
TI  - Effect of tablet splitting on serum cholesterol concentrations.
AB  - OBJECTIVE: To evaluate the effects of tablet splitting on low-density lipoprotein
      (LDL) cholesterol and total cholesterol values in patients taking simvastatin and
      atorvastatin. DESIGN: A retrospective chart review of total cholesterol and LDL
      cholesterol values of patients instructed to split simvastatin or atorvastatin
      between January 1999 and November 2000. SETTING: Veterans Affairs Medical Center
      in Huntington, WV. PATIENTS: Patients were included if they were taking
      simvastatin or atorvastatin with regular lipid management and follow-up
      laboratory results. Patients were required to remain on the same milligram-per
      day dose at least 6-8 weeks before and after tablet-splitting initiation and have
      cholesterol values drawn at least 6 weeks after initiation of both whole-tablet
      and half-tablet dosing. Patients were excluded if they had a triglyceride level >
      400 mg/dL or were noncompliant on the basis of pharmacy records and provider
      notes. MEASUREMENT OUTCOMES: The primary end points were changes in total
      cholesterol and LDL cholesterol values before and after the patient was switched
      to half-tablet therapy. RESULTS: The overall results for this review demonstrated
      no statistically significant increase in total cholesterol and LDL cholesterol
      concentrations. Total cholesterol and LDL cholesterol values actually decreased
      from presplitting to postsplitting, p = 0.017 and p = 0.003, respectively.
      CONCLUSIONS: The investigation showed that half-tablet dosing was as effective as
      whole-tablet dosing. The program will be continued as a part of quality patient
      care at the Huntington Veterans Affairs Medical Center.

PMID- 11847937
TI  - Cost-effectiveness of prophylactic indomethacin in very-low-birth-weight infants.
AB  - OBJECTIVE: To perform cost-effectiveness analysis to facilitate the decision
      making process surrounding use of indomethacin in preterm infants to lower the
      incidence of patent ductus arteriosus (PDA), intraventricular hemorrhage (IVH),
      and death. METHODS: A MEDLINE literature search from 1966 to July 2000 was
      performed to identify relevant randomized, controlled trials (RCTs), as well as
      cohort and retrospective case-control studies. A decision tree was built
      representing the choice to use or not use indomethacin, and the potential outcome
      costs. Probabilities of being in each chance node were obtained from this search.
      Where data probabilities were not clear, a sensitivity analysis was conducted.
      RESULTS: There was no difference in the expected survival per year; however,
      there was a significant difference when effectiveness was measured as quality
      adjusted life years (QALYs), resulting in 11 and 10 years for the indomethacin
      and control groups, respectively. The indomethacin treatment cost was $95,157 and
      that of the control groups was $99,955. The cost effectiveness per life
      expectancy of being in the indomethacin and control groups was $7142 and $7727,
      respectively. The sensitivity analysis for PDA closure and prevention of IVH for
      infants eventually developing PDA versus those without PDA showed no difference.
      The cost-effectiveness analysis per QALY was $8443 for the indomethacin treatment
      and $9168 for the control group. CONCLUSIONS: The prophylactic use of
      indomethacin is less costly and more effective within an important range of
      certainty. However, this analysis does not include several potentially
      confounding factors, such as antenatal steroid use or indomethacin-induced renal
      toxicity. Depending on the frequency with which these factors arise, economic
      projections may be considerably altered against the early use of indomethacin.

PMID- 11847936
TI  - Influence of standardized orders on postoperative nausea and vomiting after
      gynecologic surgery.
AB  - OBJECTIVE: The risk of postoperative nausea and vomiting (PONV) after gynecologic
      surgery remains high, despite effective prophylactic medications. Thus, the
      objectives of this study were to determine whether standardized orders for the
      prophylaxis and treatment of PONV in gynecologic surgery patients (1) reduce PONV
      occurrence, (2) reduce total costs, and (3) influence the choice of medications
      used for PONV prophylaxis and treatment. METHODS: A retrospective design was
      employed in which a random sample of 200 patients was selected from each of the
      two 6-month phases before (pre) and after (post) the implementation of
      standardized orders for PONV prophylaxis and treatment. The primary outcome was
      the occurrence of any PONV episode. Logistic regression was used to adjust for
      potential confounding factors. All costs were in 1999 Canadian dollars (Canadian
      dollar = US$0.673 in 1999). RESULTS: Characteristics were similar except for
      surgical and anesthesia length between phases. The proportion of patients who
      received PONV prophylaxis increased from 31% (pre) to 47% (post; p = 0.002).
      There was a reduction in the risk of a PONV event in the post-phase (odds ratio
      [OR] 0.67, 95% CI 0.67 to 0.97; p = 0.04). The risk of PONV was significantly
      reduced with the administration of prophylactic medications (OR 0.46, 95% CI 0.46
      to 0.67; p = 0.001). There was a reduction in the mean number of PONV episodes in
      the post-phase (1.47 events) versus the pre-phase (1.81 events; p = 0.02). A
      reduction in mean PONV management costs was observed in the post-phase ($8.31, SD
      +/- 8.50) compared with the pre-phase ($10.23, SD +/- 8.25; p = 0.02). For mean
      prophylactic costs, these were significantly higher in the postimplementation
      phase compared with the preimplementation phase ($1.64, SD +/- 3.36 vs. $0.91, SD
      +/- 2.43; p = 0.013). For mean total PONV costs (prophylaxis plus management
      costs), there was a nonsignificant reduction in the postimplementation phase
      compared with the preimplementation phase ($9.95, SD +/- 9.20 vs. $11.15, SD +/-
      8.51, respectively; p = 0.18). Univariate sensitivity analyses revealed that the
      economic results were sensitive to several parameters. CONCLUSIONS: The
      implementation of preprinted order forms for PONV prophylaxis and treatment
      appears to be an effective and economically attractive strategy.

PMID- 11847938
TI  - Brasofensine treatment for Parkinson's disease in combination with
      levodopa/carbidopa.
AB  - OBJECTIVE: To investigate the safety, tolerability, pharmacokinetic, and
      pharmacodynamic properties of the dopamine transporter antagonist brasofensine
      (BMS-204756) in patients with Parkinson's disease receiving levodopa/carbidopa
      treatment. METHODS: A 4-period crossover study was performed in 8 men (mean age
      66 y) with moderate Parkinson's disease (Hoehn-Yahr stage II-IV). A dose
      escalation study was used in which each patient was given a single oral dose of
      brasofensine 0.5, 1, 2, or 4 mg, which was coadministered with the patient's
      usual dose of levodopa/carbidopa. RESULTS: The maximum concentration (Cmax)
      values of brasofensine observed in plasma after oral administration were 0.35,
      0.82, 2.14, and 3.27 ng/mL for the 0.5-, 1-, 2-, and 4-mg doses, respectively;
      these concentrations occurred 4 hours (time to Cmax) after administration in all
      cases. Exposure to brasofensine (based on AUC0-infinity) increased at a rate
      greater than proportional to dose. Based on the motor performance subscale of the
      Unified Parkinson's Disease Rating Scale, no change in patient disability was
      observed at any dose level. CONCLUSIONS: Brasofensine was safe and well tolerated
      in the patient cohort studied at daily doses of up to 4 mg. Adverse events were
      generally mild in intensity, and included headache, insomnia, phlebitis,
      dizziness, ecchymosis, and vomiting.

PMID- 11847939
TI  - Experience with an adverse drug reaction reporting program in a neurology
      specialty clinic.
AB  - OBJECTIVE: To describe an adverse drug reaction (ADR) reporting program that was
      developed in a university-affiliated neurology specialty clinic. METHODS:
      Reportable ADRs were identified through 3 mechanisms: by clinicians through
      routine visits, by patients who were encouraged to follow up with the pharmacist
      in the clinic, and by the pharmacist who contacted high-risk patients. Patient
      demographics, the suspected drug(s), elements to define probability, and outcomes
      were documented, collated, and analyzed for trends and opportunities for
      continuous quality-improvement efforts. Information was shared with clinic
      administrators and clinicians. Serious ADRs were reported to the Food and Drug
      Administration. RESULTS: The experience during a 1-year period, during which 40
      ADRs were reported, is described. Medications by frequency of report and types of
      reactions are reported. None of the ADRs required admission to the hospital.
      Pharmacy personnel reported the majority of ADRs (92.5%). CONCLUSIONS: This
      program is successfully incorporated within daily practice and is an integral
      part of quality-improvement efforts.

PMID- 11847940
TI  - Pharmacokinetics and tolerability of lidocaine patch 5% with extended dosing.
AB  - OBJECTIVE: To assess the pharmacokinetics, safety, and tolerability of lidocaine
      delivered via 4 lidocaine 5% patches applied for 18 h/d for 3 consecutive days in
      healthy volunteers. METHODS: A prospective, nonrandomized, open-label trial was
      conducted to determine the pharmacokinetics of 4 lidocaine patches 5% applied to
      the backs of 20 volunteers on days 1, 2, and 3. On each day, serum samples were
      collected prior to, during, and after patch application. Safety and tolerability
      assessments included skin evaluations, monitoring of clinical adverse events and
      vital signs, 12-lead electrocardiograms, and laboratory testing. RESULTS: For
      days 1, 2, and 3, the mean +/- SD maximum concentrations were 145.1 +/- 42.4,
      153.0 +/- 40.7, and 153.8 +/- 51.4 ng/mL, respectively; the median times to peak
      plasma concentration were 18.0, 16.5, and 16.5 hours, respectively; the mean +/-
      SD trough concentrations were 83.0 +/- 29.0, 85.7 +/- 31.1, and 77.0 +/- 26.9
      ng/mL, respectively; and the mean +/- SD AUCs over 24 hours were 2089.2 +/-
      632.5, 2659.2 +/- 726.8, and 2675.7 +/- 819.2 ng.h/mL, respectively. The patch
      was well tolerated; local skin reactions were generally minimal and self-limited.
      CONCLUSIONS: The application of 4 lidocaine patches 5% for 18 h/d for 3
      consecutive days is well tolerated; steady-state plasma concentrations are
      achieved within 3 days. Maximum plasma concentrations of lidocaine are similar to
      those reported in a previous study with 3 lidocaine patches 5% applied for 12 h/d
      for 3 consecutive days.

PMID- 11847941
TI  - Evaluation of mexiletine clearance in a Japanese population.
AB  - OBJECTIVE: To evaluate mexiletine clearance in a Japanese population and to
      clarify the roles of CYP2D6 and CYP1A2 in mexiletine disposition. METHODS:
      Concentrations of serum and urinary mexiletine and its metabolites were
      determined and mexiletine clearances were estimated in 334 inpatients receiving
      mexiletine therapy. Concentrations of mexiletine and its metabolites in serum and
      urine samples were determined by HPLC. RESULTS: Although interindividual
      variation of mexiletine clearance was small, the effect of age on mexiletine
      clearance was comparatively large. Mexiletine clearance in patients with dilated
      cardiomyopathy (DCM) was decreased when compared with other diagnoses (Non-DCM).
      The fractional contents of p-hydroxymexiletine (POH) and 2-hydroxymexiletine
      (OHMEX) in urine amounted to approximately 50%. Almost all of the POH was
      conjugated, whereas less than one-third of the OHMEX was conjugated. Although no
      significant differences in POH and OHMEX were observed between patients with DCM
      and those without, a trend toward an increase in conjugation pathway of DCM
      patients was observed. CONCLUSIONS: The interindividual variation of mexiletine
      clearance was small, while the effect of age on the mexiletine clearance in Non
      DCM was comparatively large. A significant difference in mexiletine clearance
      between patients with DCM and those with Non-DCM was observed. Therefore, when
      mexiletine is administered to patients with DCM, careful monitoring is needed.

PMID- 11847942
TI  - In vitro assessment of urinary isolates of ampicillin-resistant enterococci.
AB  - OBJECTIVE: Susceptibility and minimum inhibitory concentration (MIC) studies of
      ampicillin-resistant enterococci (ARE) were performed with vancomycin,
      ciprofloxacin, and trovafloxacin. Ampicillin MICs were determined to make
      comparisons with achievable urinary concentrations of ampicillin. DESIGN: From
      July 1998 to April 1999, all enterococci isolated from urinary specimens were
      tested for susceptibility to ampicillin by disk diffusion. For all ARE,
      vancomycin, ciprofloxacin, and trovafloxacin susceptibilities were determined by
      use of either disk diffusion or the E-test. Ampicillin MICs were determined for
      these isolates by liquid agar microdilution testing. ARE were identified to the
      species level on the basis of biochemical reactions. SETTING: The study was
      performed at a university-affiliated tertiary care hospital. OUTCOME MEASURES: In
      vitro susceptibility studies and MIC determinations were performed in accordance
      with the National Committee for Clinical Laboratory Standards. RESULTS: A total
      of 310 urine samples were culture positive for enterococcus. Thirty (9.7%)
      unduplicated isolates were resistant to ampicillin. Of these, nine ARE isolates
      (30%) were also vancomycin resistant, whereas only 2 ampicillin-susceptible
      isolates were vancomycin resistant (p < 0.05). All ARE were resistant to
      ciprofloxacin, and 29 (96.7%) were resistant to trovafloxacin. Nine (30%), 18
      (60%), and 3 (10%) isolates had an ampicillin MIC of 128, 256, and 512
      micrograms/mL, respectively. Ampicillin MICs did not differ significantly between
      vancomycin-susceptible and -resistant isolates (p = 0.963). Twenty-seven isolates
      (90%) were identified as Enterococcus faecium; the other 3 were either
      Enterococcus avium or Enterococcus raffinosus. CONCLUSIONS: Ampicillin resistance
      is associated with resistance to vancomycin. Most ARE are resistant to
      fluoroquinolone antibiotics such as ciprofloxacin and trovafloxacin. Ampicillin
      MICs for ARE found in these urinary specimens were all within 1 dilution of 256
      micrograms/mL, a concentration achievable in the urine with higher doses of oral
      amoxicillin or intravenous ampicillin. Additional studies are needed to assess
      the clinical implications of these data.

PMID- 11847943
TI  - Bupropion-induced acute dystonia.
AB  - OBJECTIVE: To report a case of acute dystonia consisting of neck stiffness,
      trismus, and unilateral temporomandibular joint (TMJ) pain and subluxation
      secondary to an increase in sustained-release (SR) bupropion. CASE SUMMARY: A 44
      year-old white man with a history of chronic low-back pain and tension headaches,
      taking no other medications, was started on bupropion SR 150 mg once a day for
      depression. The dosage was increased to 150 mg SR twice a day and eventually
      augmented with buspirone 15 mg 3 times a day. He developed bilateral trismus,
      inability to rotate his head laterally, and spontaneous left TMJ subluxation.
      Symptoms recessed with discontinuation of both medications and failed to reappear
      with a trial of buspirone 15 mg 3 times a day alone. A retrial of bupropion alone
      evidenced no adverse effects at a dosage of 150 mg SR once a day. However, when
      the dosage was increased to 150 mg SR twice a day, the patient reexperienced
      initial signs of neck stiffness, jaw muscle tightness, and left TMJ subluxation
      within 24-48 hours. Reduction of the bupropion dosage to 150 mg SR once daily
      stopped the symptoms; the patient has continued at this dosage without adverse
      effects for > 1 year. DISCUSSION: Medication-induced focal dystonias usually
      present with dramatic head (most frequently oral-buccal) and neck muscle spasm
      with occasional jaw clenching, bruxism, and TMJ syndrome. In this case, the rapid
      onset of neck and jaw symptoms within 24-48 hours of an increase of bupropion SR
      from 150 mg once a day to 150 mg twice a day suggest that the patient may have
      been sensitized by an initial trial of bupropion and buspirone, or by the
      increased dose of bupropion alone. Both agents are reported to interact with both
      the dopaminergic and serotonergic systems. Although buspirone has been implicated
      in inducing acute dystonia, it did not do so in this case when used alone at a
      dose of 45 mg a day. During a second trial of bupropion SR 150 mg a day, neck and
      jaw symptoms recurred within 24-48 hours of increasing the dose to 150 mg SR
      twice a day. The symptoms receded when the bupropion dose was returned to 150 mg
      SR once a day, suggesting a dose-response relationship. The Naranjo probability
      scale indicated that this untoward reaction was probable. CONCLUSIONS: This case
      suggests that selected patients may experience dose-related acute dystonic
      adverse reactions to bupropion with or without buspirone augmentation. Dystonias,
      which usually follow administration of antipsychotics, have been linked to acute
      dopamine depletion and basal ganglion-derived gamma synchronization dysfunction.
      Acute dystonia symptoms may begin within hours of starting or changing
      antipsychotic drug dosage; however, 90% of symptoms are observed during the first
      3-5 days of starting or increasing dosage. To the best of our knowledge, there
      have been no reports of bupropion-induced dystonia.

PMID- 11847944
TI  - High-dose oral magnesium treatment of chronic, intractable erythromelalgia.
AB  - BACKGROUND: Previous studies with magnesium have shown beneficial effects in pain
      syndromes and in vascular disorders (hypertension, migraines, Raynaud's
      phenomenon). However, results have been variable, possibly because of the limited
      oral doses achievable due to frequent diarrhea. OBJECTIVE: To describe the case
      of a 53-year-old white man (the author) with disabling erythromelalgia (EM) who
      achieved modest improvement limited by adverse effects with calcium antagonists
      and then obtained remission with the use of magnesium. Intolerant of several
      standard magnesium products, he attained high doses of magnesium by taking
      intravenous-grade magnesium sulfate diluted in water orally (up to 24 mL/d of
      MgSO4 50% = 1166 mg/d of magnesium). METHODS: After 12 months of continued
      improvement, patient 1, a board member of The Erythromelalgia Association,
      notified other members of the success of this therapy via an Internet
      communication channel. He encouraged those interested in high-dose magnesium
      therapy to consult their physicians and to report their results to the
      Association. Twelve patients responded to this request, describing several
      standard oral magnesium products. RESULTS: Overall, 8 of 13 patients (61.5%)
      reported improvement (1, remission; 3, major improvement; 2, moderate
      improvement; 2, mild improvement). Four patients (30.8%) reported no response to
      magnesium therapy, and 1 patient's symptoms worsened. Two patients' magnesium
      dose was limited because of diarrhea. CONCLUSIONS: Despite recent progress in
      understanding and treating EM, this vascular disorder remains painful and life
      altering for many patients. In this informal survey, the use of high oral doses
      of magnesium produced good and sometimes dramatic results in 8 of 13 patients who
      had been unresponsive to many other treatments. These results suggest a possible
      role for high-dose oral magnesium in the treatment of EM and, perhaps, other
      vascular disorders.

PMID- 11847945
TI  - Acute cholestatic hepatitis after exposure to isoflurane.
AB  - OBJECTIVE: To report a case of acute cholestatic hepatitis following exposure to
      the inhalational anesthetic isoflurane. CASE SUMMARY: A 70-year-old healthy woman
      from Iraq developed acute cholestatic hepatitis 3 weeks following repair of the
      right rotator cuff under general anesthesia. There was no evidence for viral,
      autoimmune, or metabolic causes of hepatitis. No other medications were involved
      except for dipyrone for analgesia. The alanine aminotransferase was elevated to a
      peak concentration of 1533 U/L and the serum bilirubin reached a peak of 17.0
      mg/dL. There was slow improvement over 4 months. Accidental reexposure by the
      patient to dipyrone was uneventful. DISCUSSION: The clinical and histologic
      picture of this case resembles halothane hepatitis, which has a significant
      mortality rate. CONCLUSIONS: Isoflurane, a common anesthetic agent, can cause
      severe cholestatic hepatitis.

PMID- 11847946
TI  - Idiopathic paresthesia reaction associated with rofecoxib.
AB  - OBJECTIVE: To report a case of a paresthesia-type reaction due to the use of
      rofecoxib in standard doses for the treatment of osteoarthritis. CASE SUMMARY: A
      55-year-old white woman was receiving rofecoxib for treatment of osteoarthritis.
      The patient began to have tongue numbness and hand tingling and numbness shortly
      after starting therapy with rofecoxib. The occurrence and resolution of her
      symptoms correlated with the start and end of the therapy. DISCUSSION: An adverse
      reaction with rofecoxib is a likely explanation for the patient's symptoms.
      Paresthesias have been reported in 0.1-1.9% of patients who took rofecoxib during
      premarketing studies, but no causality has been established. One case report of
      paresthesias occurring in a 59-year-old white man who took one 20-mg dose of
      piroxicam is available. Information on when the reaction occurred in relation to
      the dose and resolution of the reaction was not recorded in this study. Our
      patient's reaction is best classified as idiopathic. CONCLUSIONS: We report the
      first case of a paresthesia-type reaction to rofecoxib in a patient receiving the
      drug in standard doses for treatment of osteoarthritis. Although the reaction is
      rare, clinicians should be aware of its potential.

PMID- 11847947
TI  - Agranulocytosis associated with initiation of famotidine therapy.
AB  - OBJECTIVE: To report a case of agranulocytosis associated with initiation of
      famotidine. CASE SUMMARY: An 87-year-old white man was admitted to the internal
      medicine department of an acute care hospital because of fever and
      agranulocytosis (granulocyte count 0). Eight days prior to admission, famotidine
      therapy had been initiated. Famotidine was discontinued and granulocyte
      macrophage colony stimulating factor was administered, with concomitant recovery
      of the granulocyte count and subsequent development of a leukemoid reaction.
      DISCUSSION: According to the Naranjo probability scale, famotidine was the
      probable cause of agranulocytosis. This is a rare adverse effect of this
      medication; only a few other cases have been reported. CONCLUSIONS: Although
      agranulocytosis is a rare adverse effect of famotidine, the pharmacist and
      physician should be aware of this potentially fatal event. If any patient treated
      with famotidine develops fever, the clinician should consider, among other
      things, performing a white blood cell count.

PMID- 11847948
TI  - Alteplase use for prevention of central line occlusion in a preterm infant.
AB  - OBJECTIVE: To report the use of alteplase for catheter clearance in a neonate of
      27 weeks' gestation at day 50 of life. SETTING: Neonatal Intensive Care Unit,
      Naval Medical Center. CASE SUMMARY: At day 50 of life, a neonate boy of 27 weeks'
      gestation had a clotted peripherally inserted central catheter line. He required
      central access to complete a 28-day course of amphotericin B. An alteplase dose
      of 0.3 mg/0.3 mL was instilled into the catheter, for an indwelling time of 1
      hour. The initial attempt was successful, and the patient was able to finish the
      course of amphotericin B. DISCUSSION: When a catheter becomes occluded, the cause
      must be determined initially; then an appropriate treatment option can be
      initiated. Hydrochloric acid and ethanol are some of the pharmacologic agents
      available, with their use dependent on the precipitating cause of the occlusion.
      Thrombolytic agents, such as streptokinase and urokinase, have also been used in
      catheter clearance. The potential risk of anaphylactic reactions with
      streptokinase and the unavailability of urokinase have clinicians searching for
      other pharmacologic alternatives. Alteplase, a synthetic tissue plasminogen
      activator, has been shown to be a promising alternative agent. There are various
      reports of alteplase use in pediatric patients for catheter clearance, with
      different suggested doses ranging from 0.25 to 2 mg. To minimize the risk of
      bleeding events, initiation with low doses from the suggested range is
      recommended. CONCLUSIONS: Alteplase was shown to be safe and effective for
      clearance of an occluded central line in a preterm infant.

PMID- 11847949
TI  - Pancreatitis associated with simvastatin plus fenofibrate.
AB  - OBJECTIVE: To report a case of acute necrotizing pancreatitis associated with
      simvastatin and fenofibrate use. CASE SUMMARY: A 70-year-old white man presenting
      with rapid onset of abdominal pain, nausea, and vomiting was diagnosed with acute
      pancreatitis. On bowel rest, his condition deteriorated secondary to systemic
      inflammatory response syndrome, and he was transferred to a tertiary hospital's
      intensive care unit (ICU). He had been taking fenofibrate for 1 year; 6 months
      prior to this admission, he had been taking simvastatin 3 days of the week and
      fenofibrate the other 4 days of the week. The pancreatic tissue became necrotic,
      requiring surgical debridement. After a hospital stay of 121 days, including
      multiple ICU admissions, the patient died secondary to a bowel perforation.
      DISCUSSION: Although idiopathic pancreatitis cannot be ruled out in this patient,
      no causes of pancreatitis were identified other than drug induced. Five cases of
      acute pancreatitis caused by simvastatin have been reported; no case reports were
      found for fenofibrate. The onset of pancreatitis relative to the duration of
      therapy with simvastatin supports this medication as a possible cause of the
      pancreatitis. CONCLUSIONS: Drug-induced pancreatitis is well established as an
      adverse effect of some medications, although most are substantiated only with
      case reports. Given the absence of other apparent causes, simvastatin and
      fenofibrate should be considered as possible causes of pancreatitis in this
      patient.

PMID- 11847951
TI  - FDA adverse event reports on statin-associated rhabdomyolysis.
AB  - OBJECTIVE: To determine the number of cases of statin-associated rhabdomyolysis
      reported to the Food and Drug Administration for 6 statins and to profile the
      cases. METHODS: A retrospective analysis of all domestic and foreign reports of
      statin-associated rhabdomyolysis between November 1997 and March 2000 was
      conducted. Outcome measures included the total number of reports (initial plus
      follow-up), the number of unique cases, age, gender, percentages of report codes
      and role codes, and frequencies of concomitant interacting drugs that may have
      precipitated rhabdomyolysis, outcomes codes, and report source codes. RESULTS:
      There were 871 reports of statin-associated rhabdomyolysis in the 29-month time
      frame examined, representing 601 cases. The following number of cases were
      associated with each of the individual statins: simvastatin, 215 (35.8%);
      cerivastatin, 192 (31.9%); atorvastatin, 73 (12.2%); pravastatin, 71 (11.8%);
      lovastatin, 40 (6.7%); and fluvastatin, 10 (1.7%). Drugs that may have interacted
      with the statins were present in the following number of cases: mibefradil (n =
      99), fibrates (n = 80), cyclosporine (n = 51), macrolide antibiotics (n = 42),
      warfarin (n = 33), digoxin (n = 26), and azole antifungals (n = 12). The reports
      of 62.1% of cases were classified as expedited. Statins were designated as the
      primary suspect in 72.0% of the cases. Death was listed as the outcome in 38
      cases. The majority of reports (n = 556) were from health professionals.
      CONCLUSIONS: Compared with the other statins, simvastatin and cerivastatin were
      implicated in a relatively higher number of reports. Because of the various
      limitations of a spontaneous reporting-system database, caution is urged when
      interpreting the relative number of cases reported.

PMID- 11847950
TI  - Viral load as a surrogate end point in HIV disease.
AB  - OBJECTIVE: To examine the role of viral load as a surrogate end point for HIV
      disease progression and death. DATA SOURCES: A MEDLINE search was conducted for
      the years 1990-March 2001. In addition, relevant articles were cross-referenced
      to screen for additional information. STUDY SELECTION AND DATA EXTRACTION: Data
      regarding the validity of viral load as a surrogate end point for disease
      progression or death are cited. Emphasis was placed on randomized, controlled
      trials, but descriptive studies are also included. DATA SYNTHESIS: Recently,
      viral load has emerged as an important biomarker for monitoring HIV disease and
      antiretroviral therapy. Both baseline viral load and changes in viral load with
      time predict HIV disease progression and death. In fact, disease progression
      increases consistently once viral load exceeds 10,000 copies/mL, and AIDS and
      death primarily occur in patients with viral loads > 100,000 copies/mL. Changes
      that occur in viral load after initiation of antiretroviral therapy, however, do
      not fully explain the entire treatment effect. Also, separate comparisons of
      antiretroviral regimens may demonstrate similar differences in viral load changes
      but not similar differences in disease progression. CONCLUSIONS: Viral load is an
      important monitoring parameter for HIV disease and antiretroviral therapy.
      However, changes in viral load do not explain the entire clinical improvement
      that occurs after initiation of therapy. Although viral load is a clinically
      important surrogate end point for HIV disease, it cannot fully account for all
      associated treatment effects.

PMID- 11847952
TI  - Levetiracetam: a different approach to the pharmacotherapy of epilepsy.
AB  - OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, and adverse
      effects of levetiracetam in the treatment of epilepsy. DATA SOURCES: A MEDLINE
      search restricted to English-language publications was conducted (January 1993
      October 2000). Unpublished data provided by the manufacturer and information
      found in proceedings of professional meetings were also included. DATA
      EXTRACTION/STUDY SELECTION: Information regarding basic pharmacology was
      collected from studies in animals. Pharmacokinetic data were collected from human
      trials. Only randomized, placebo-controlled clinical trials were included to
      describe the efficacy and safety of levetiracetam. DATA SYNTHESIS: Levetiracetam
      is a new antiepileptic drug (AED) that appears to work by a unique mechanism.
      Animal studies have shown that levetiracetam may prevent epileptogenesis.
      Levetiracetam is rapidly and completely absorbed, minimally bound to plasma
      proteins, eliminated through the kidneys, and has a half-life of 6-8 hours. Doses
      must be adjusted for varying degrees of renal function. In clinical trials,
      levetiracetam significantly decreased seizure frequency compared with placebo
      when added to existing AED regimens. One clinical trial indicated that
      levetiracetam may be effective as monotherapy. Few major adverse effects were
      reported in the clinical trials; however, several patients reported psychological
      and psychotic reactions. CONCLUSIONS: Levetiracetam is a safe and effective new
      AED. Its apparent unique mechanism of action makes levetiracetam an important
      addition to therapy with older medications. Caution should be exercised when
      administering levetiracetam to individuals who may be prone to psychotic or
      psychiatric reactions.

PMID- 11847953
TI  - Secretin for the treatment of autism.
AB  - OBJECTIVE: To evaluate the role of secretin in the treatment of children with
      autism. DATA SOURCE: Literature was assessed through MEDLINE, EMBASE, BIOSIS
      (November 1998-August 2001), and the World Wide Web. Literature included
      scientific studies, anecdotal reports, and meeting abstracts. Key search terms
      included autism and secretin. DATA SYNTHESIS: Autism is a pervasive developmental
      disorder. Although several treatments exist, no cure has been identified. New
      information suggests that secretin may be beneficial for this disorder. A
      critical evaluation of current information about the use of secretin in autism
      was conducted. CONCLUSIONS: Currently, several anecdotal reports and a few
      controlled trials with conflicting results have been published regarding the use
      of secretin in autism. Further studies should be conducted to determine the
      safety and efficacy of secretin for autism.

PMID- 11847955
TI  - Role of budesonide inhalation suspension in children with asthma.
AB  - OBJECTIVE: To evaluate the role of budesonide inhalation suspension (BIS) in the
      treatment of children with asthma. DATA SOURCES: Literature identified through
      Medline (1966-November 2000) and references obtained from selected articles.
      Search terms included budesonide and asthma. DATA SYNTHESIS: Asthma is a chronic
      inflammatory disease that affects approximately 4.8 million children in the US.
      By reducing inflammation, corticosteroids decrease symptoms and improve lung
      function. As the first nebulized corticosteroid, BIS offers an important
      treatment option for children with persistent asthma. CONCLUSIONS: BIS is
      effective in reducing symptoms and improving lung function in children with
      asthma. It should be used in children ages 1-8 years with moderate to severe
      persistent asthma who are unable to effectively use a metered-dose inhaler with
      or without a spacer or a dry-powder inhaler.

PMID- 11847954
TI  - Opioid dependence treatment, including buprenorphine/naloxone.
AB  - OBJECTIVE: To review opioid dependence (OD) and its treatment. Pharmacologic
      treatments, including the use of buprenorphine/naloxone, are presented.
      Pharmaceutical care functions for outpatient OD treatment are discussed. DATA
      SOURCES: Primary and review articles were identified by MEDLINE and HEALTHSTAR
      searches (from 1966 to November 2000) and through secondary sources. Tertiary
      sources were also reviewed regarding general concepts of OD and its treatment.
      STUDY SELECTION/DATA EXTRACTION: Relevant articles were reviewed after
      identification from published abstracts. Articles were selected based on the
      objectives for this article. Studies of the treatment of OD with buprenorphine
      were selected based on the topic (pharmacology, pharmacokinetics, adverse
      reactions) and study design (randomized, controlled clinical trials in patients
      with OD with active/placebo comparisons and/or comparisons of active OD
      treatments). Articles regarding pharmacists' activities in the treatment and
      prevention of OD were reviewed for the pharmaceutical care section. DATA
      SYNTHESIS: OD is considered a medical disorder with costly adverse health
      outcomes. Although methadone maintenance treatment (MMT) is cost-effective for
      OD, only about 12% of individuals with OD receive this treatment. Psychological
      and pharmacologic modalities are used to treat OD, but patients often relapse.
      Drug therapy includes alpha 2-agonists for withdrawal symptoms, detoxification
      regimens with or without opioids, opioid antagonists, and opioid replacement
      including methadone, levomethadyl acetate, and buprenorphine. The Drug Addiction
      Treatment Act of 1999 allows for office-based opioid replacement therapies.
      Sublingual buprenorphine with naloxone can be used in this milieu. Buprenorphine
      with naloxone is currently under new drug application review with the Food and
      Drug Administration. Clinical research shows buprenorphine to be equal in
      effectiveness to methadone, but safer in overdose due to its ceiling effect on
      respiratory depression. It has lower abuse potential and fewer withdrawal
      symptoms when discontinued. Naloxone is included to decrease diversion and
      injection of the tablets. Pharmacists in outpatient settings who are familiar
      with OD have opportunities to provide pharmaceutical care to patients receiving
      this treatment. Pharmaceutical care functions for OD include ensuring appropriate
      drug administration, monitoring adverse effects, alleviating withdrawal symptoms,
      treating intercurrent illnesses, minimizing diversion, and preventing relapse.
      CONCLUSIONS: OD is a critical unmet health problem in the US. Buprenorphine
      combined with naloxone represents an innovative treatment for OD in outpatient
      settings. This new treatment has advantages over MMT.

PMID- 11847956
TI  - Hydroxymethylglutaryl-coenzyme A reductase inhibitors in osteoporosis management.
AB  - OBJECTIVE: To evaluate the use and potential benefit of hydroxymethylglutaryl
      coenzyme A (HMG-CoA) reductase inhibitors (statins) in the management of
      osteoporosis. DATA SOURCES: Clinical literature accessed through MEDLINE (1994
      May 2001) using the key search terms HMG-CoA reductase inhibitors, statins,
      osteoporosis, and fractures. DATA SYNTHESIS: Osteoporosis is the most common bone
      disease, affecting millions of people worldwide and leading to significant
      morbidity and high expenditures, especially when it is not adequately managed.
      Recent data have documented a potential association between statin use and
      improvement in fracture risk profile. Therefore, an evaluation of studies
      investigating the effect of HMG-CoA reductase inhibitors on bone and fracture
      risk was conducted. CONCLUSIONS: Observational studies suggest an association
      between HMG-CoA reductase inhibitors and reduction in fracture risk. However,
      large randomized controlled studies are needed to confirm this association.

PMID- 11847957
TI  - Hepatotoxicity associated with chronic acetaminophen administration in patients
      without risk factors.
AB  - OBJECTIVE: To evaluate the literature regarding the potential of acetaminophen to
      cause toxicity in adult patients without risk factors, when used chronically in
      daily doses < or = 4 g. DATA SOURCES: Key tertiary literature was reviewed, along
      with searches of MEDLINE (1966-July 2001). International Pharmaceutical Abstracts
      (1970-May 2001), and PREMEDLINE (July Week 5, 2001). Key search terms included
      acetaminophen, paracetamol, toxic hepatitis, hepatotoxicity, liver dysfunction,
      overdose, drug toxicity, and poisoning. DATA SYNTHESIS: Most tertiary references
      state that the maximum daily dose of acetaminophen is 4 g. Patients taking more
      than this amount, especially those with certain risk factors, are more likely to
      develop toxicity. However, a few patients may develop toxicity regardless of
      risk. An evaluation of the literature regarding the toxic potential of
      acetaminophen when given at doses < or = 4 g/d chronically (> or = 4 d) to adult
      patients without risk factors was conducted. CONCLUSIONS: Acetaminophen should be
      used cautiously on a chronic basis because several case reports show that it may
      be hepatotoxic at therapeutic doses.

PMID- 11847958
TI  - Anthrax: safe treatment for children.
AB  - Information regarding the treatment of anthrax infection is scarce in adults and
      is even more limited in children. Children, however, may be at a greater risk for
      developing an infection and systemic disease if exposed to anthrax than adults.
      The Centers for Disease Control and Prevention (CDC) recommends the use of
      doxycycline or ciprofloxacin for prophylaxis and treatment in children.
      Doxycycline currently is not indicated for use in children < 8 years old, due to
      staining of teeth and inhibition of bone growth associated with tetracyclines.
      Doxycycline, however, may have less adverse effect on teeth than its precursors.
      Ciprofloxacin has a pediatric indication only when a child is potentially exposed
      to inhaled anthrax. Ciprofloxacin is contraindicated in pediatric patients
      because fluoroquinolones were shown to cause cartilage toxicity in immature
      animals. Although children of various ages have received ciprofloxacin, there are
      few reports of cartilage toxicity. Because anthrax is a potentially fatal
      infection, the benefits to using these antibiotics greatly outweigh the risks.
      Therefore, the use of these antibiotics in children can be recommended, despite
      the lack of adequate efficacy and safety studies in pediatric patients with
      anthrax.

PMID- 11847959
TI  - Use of cisapride with contraindicated drugs in The Netherlands.
AB  - OBJECTIVE: To investigate the prevalence of concomitant use and coprescribing of
      cisapride with potentially interacting drugs to evaluate the impact of these
      warnings from 1994 to 1998. DESIGN: Retrospective follow-up study of patients
      using cisapride. SETTING: Data for this study were obtained from the pharmacy
      database of the Dutch PHARMO record linkage system (n = 834,000). RESULTS: From
      1994 to 1998, the prevalence rate of the observed versus expected use of any
      potentially interacting drug decreased significantly over time (p < 0.01).
      However, the number of days-at-risk and number of coprescriptions of potentially
      interacting drugs among cisapride users increased on average by 13% and 9% per
      year, respectively. This increase was almost exclusively explained by a large
      increase in concomitant prescribing of clarithromycin, the most commonly used
      potentially interacting drug. Decreases in prevalence rates were observed for all
      individual potentially interacting drugs, except for concomitant use of
      fluconazole and miconazole. CONCLUSIONS: Over the last few years, healthcare
      professionals have refrained from dispensing potentially interacting drugs to
      patients who use cisapride, probably as a result of drug warnings implemented
      during this period. The limited absolute effects result from an increase of
      coprescription and concomitant use of clarithromycin and fluconazole among
      cisapride users. Because therapeutically equivalent alternatives were available
      for both drugs, such combinations were avoidable. Communicating information on
      these drug-drug interactions to prescribers and pharmacists and inclusion of
      cardiovascular morbidity as a relative contraindication for prescribing cisapride
      with these drugs may substantially decrease the risk of potentially adverse
      events to cisapride.

PMID- 11847961
TI  - Probable interaction between citalopram and acenocoumarol.

PMID- 11847960
TI  - Multiple fixed-drug eruption and diarrhea with ticlopidine.

PMID- 11847962
TI  - Formulas for calculating body surface area.

PMID- 11847963
TI  - [Clinical problems of orthodontics and orofacial orthopedics at the turn of the
      millennium].
AB  - The author gives an overview of orthodontic profession among the dental
      specialties. Educational problems of orthodontics in the new age are also
      discussed as well as treatment quality assurance possibilities and conditions.
      Future treatment possibilities of retrospectively rehabilitative adult
      orthodontics and interceptively prospective early treatment of children are
      referred. The article also cover the 3D imaging of the human face, animation of
      the craniofacial complex, and Cephalometric 3D analysis as areas of scientific
      research and realities. The need for restandardizing of orthodontic slot size to
      simplify and to minimize changeover problems in orthodontics basic hardware--the
      wires and brackets--are also addressed.

PMID- 11847964
TI  - [Investigation of the relationship between the posterior edge of the base of
      complete lower dentures and the mandibular tuberculum].
AB  - Surveying the data published in the literature one can establish that opinions of
      authors differ concerning the appropriate relationship between complete lower
      dentures and the tuberculum alveolare mandibulae (TAM). Some authors claim that,
      following extensional principles, the base of complete lower dentures must fully
      cover the TAM. Others think that it is enough if the base covers half of the TAM;
      yet others recommend that the base should merely extend as far as the mesial edge
      of the TAM. In the present investigations, we tried to find out what the
      relationship was between complete lower dentures prepared in everyday practice
      and the TAM. Dentists of the Clinic of Prosthetic Dentistry examined 8346
      patients in eight different regions of Hungary over a period of three years. In
      the present analysis, we discuss the data of subjects wearing a complete lower
      denture. In the populations concerned, 669 subjects met these criteria. With
      respect to the relationship between the base and the TAM, we distinguished three
      groups. The first group was made up by cases where the base extended as far as
      the mesial edge of the TAM, the second group included subjects whose base reached
      the medial line of the TAM, whereas the third group comprised patients in whose
      case the base fully covered the TAM. The relationship between the base and the
      TAM was examined intraorally, by ocular inspection. The data were analysed with
      regard to gender and laterality, by the help of the SPSS software package and the
      chi 2 test. The investigations showed that, in everyday practice, an overwhelming
      majority (77.10%) of complete lower dentures had a base extending to the mesial
      edge of the TAM, and it was in a mere 3.9% of cases that the base covered (some
      of) the TAM. Cases where the edge of the base did not reach the TAM (19.01%) were
      taken as cases where the dentist disregarded the significance of the relationship
      between the base and the TAM. The tuberculum alveolare mandibulae is a structure
      made up by dense fibrous connective tissue that, in most cases, may get displaced
      over its base and is not pressure resistant, not able to provide a value-like
      seal and, therefore, not suitables for the extension of the base. Our results
      suggest that practising dentists have noticed this; furthermore, they have
      probably also noticed that whenever the base extends as far as the mesial edge of
      the TAM, leaning against it as it were, it effectively prevents the denture from
      shifting backwards, i.e. is an obstacle to its anteroposterior displacement.

PMID- 11847965
TI  - [Mathematical description of human root canal curvatures].
AB  - There is a necessity of a mathematical formula for the description of root canal
      curvatures. The aim of this study was to give a mathematical description of root
      canal forms. The measurements of 60 roots were conducted on isometric radiographs
      taken from the clinical view. Seven points of the imaginary axis were
      approximated using fourth-degree polynomial functions. Fourth-degree
      approximation for the description of the shape of root canal curvatures proved to
      be exact and reliably repeatable. This method may serve the classification of
      root canal forms as well as the description of the spatial curve of root canals.

PMID- 11847966
TI  - [Electron microscopic examination of the surface morphology of dental implants].
AB  - The surface morphology of implants plays a considerable role in their long-term
      stability. The authors summarise the results of their research of the surface
      morphology of dental implants. They describe in detail the methods of
      manufacturing the surface and their analysis. In their study the SEM was used for
      surface analysis.

PMID- 11847967
TI  - [Stomatologic significance of masticatory system types].
AB  - The author gives analysis on the importance of the constitutional types of the
      masticatory system in the fields of restorative dentistry, oral surgery,
      prosthodontics and orthodontics. According to his research there are two types:
      I. High alveolar process, the teeth have long roots and short crowns. II. Low
      alveolar process, the teeth have shorter roots and longer crowns. The two groups
      may be differentiated by measurement of the height of the upper alveolar process
      in the median line (anthropologic points: nasospinale, prosthion) and the lengths
      of the anatomic crown of the upper medial incisor.

PMID- 11847968
TI  - [Effectiveness of various procedures and instruments used in root canal treatment
      for reducing bacterial growth (in vitro comparison)].
AB  - In this study root canal preparation methods and instruments were compared by
      using forty extracted upper first bicuspids. The trepanated and extirpated teeth
      were sterilised in an autoclave, inoculated with Enterococcus faecalis and
      incubated for 24 hours at 37 degrees C. The teeth were divided into 5 groups as
      follows: those treated with K-file and K-file Nitiflex (step back technique, 1st,
      2nd groups), with K-reamer (standard technique, 3rd group), those rinsed only
      with sterile saline solution (4th group), and those left untouched after
      incubation (5th group). Bacterial samples were taken before and after preparation
      and were inoculated onto special E67 plates. The plates were evaluated after 24
      hours of incubation. It was concluded that the number of the bacteria could be
      significantly reduced with rinsing and mechanical preparation. There was no
      significant difference as to the efficacy of the preparation procedures or
      instruments applied.

PMID- 11847969
TI  - Interrenal stress responsiveness of marbled sole, Pleuronectes yokohamae,
      inhabiting Tokyo Bay.
AB  - The interrenal stress responsiveness of marbled sole (Pleuronectes yokohamae)
      captured in the interior (Tokyo) and at the mouth (the Uraga Strait; Uraga) of
      Tokyo Bay, in the coastal region of Onjuku (the eastern coastal region of Chiba
      prefecture; Pacific) and in Ishinomaki Bay (Ishinomaki) in Japan was
      investigated. That is, the effects of air-exposure on plasma cortisol and glucose
      levels in the fish from the four different regions, and the effect of in vitro
      ACTH treatment on cortisol release from the head kidney tissue of the fish held
      under resting conditions were examined. In this study, it was found that (i)
      there were no significant differences in plasma cortisol and glucose levels among
      the fish from the four different regions under resting conditions, (ii) each air
      exposed fish increased plasma cortisol and glucose levels, (iii) the cortisol
      response in marbled sole inhabiting Tokyo Bay, in particular the interior, was
      lower, delayed and prolonged, and (iv) cortisol release from the head kidney to
      in vitro ACTH treatment was lower in the fish from Tokyo compared with the fish
      from the reference (not so polluted) sites, Pacific and Ishinomaki. These results
      suggest that marbled sole inhabiting Tokyo Bay, in particular the interior, have
      been altered in their responsiveness of cortisol-producing interrenal cells to
      the stressor in the hypothalamus-pituitary-interrenal (HPI) axis.

PMID- 11847970
TI  - Structure-activity relationships for gene activation oestrogenicity: evaluation
      of a diverse set of aromatic chemicals.
AB  - Structure-activity relationships for oestrogenicity were developed based on 120
      aromatic chemicals evaluated in the Saccharomyces cerevisiae-based Lac-Z reporter
      assay. Relative gene activation was compared to 17 beta-estradiol and varied over
      eight orders of magnitude. Analysis of the data compared to 17 beta-estradiol
      identified three structural criteria that were related to xenoestrogen activity
      and potency: (1) the hydrogen-bonding ability of the phenolic ring mimicking the
      A-ring, (2) a hydrophobic centre similar in size and shape to the B- and C-rings,
      and (3) a hydrogen-bond donor mimicking the 17 beta-hydroxyl moiety of the D
      ring, especially with an oxygen-to-oxygen distance similar to that between the 3-
      and 17 beta-hydroxyl groups of 17 beta-estradiol. Binding data were segregated
      into activity clusters including strong, moderate, weak, and detectable gene
      expression, and those compounds that were inactive. The hydrogen-bonding ability
      of hydroxy group in the 3-position on 17 beta-estradiol was observed to be
      essential for gene activation. Compounds with a 4-hydroxyl substituted benzene
      ring and a hydrophobic moiety of size and shape equivalent to the B-ring of 17
      beta-estradiol were generally observed to be weakly active compounds. Moderately
      active compounds have a 4-hydroxyl substituted benzene ring with a hydrophobic
      moiety equivalent in size and shape to the B- and C-ring of 17 beta-estradiol, or
      have a high hydrogen-bond donor capacity owing to the presence of halogens on a
      nonphenolic ring. Strongly active compounds, similar to 4,4'-diethylethylene
      bisphenol (DES), possess the same hydrophobic ring structure as described for
      moderately active compounds and an additional hydroxyl group with an oxygen-to
      oxygen distance close to that exhibited by the 3- and 17-hydroxyl groups of 17
      beta-estradiol.

PMID- 11847971
TI  - Toxicology of a Microcystis ichthyoblabe waterbloom from Lake Oued Mellah
      (Morocco).
AB  - In the Lake Oued Mellah cyanobacteria waterblooms occur periodically in late
      spring and summer with Microcystis ichthyoblabe as the main bloom-forming
      species. In 1999, a heavy waterbloom of M. ichthyoblabe occurred during May June
      with a maximal biomass of 298 mg/l. During this period, several bloom samples
      were collected. The toxicity assessment was done by mouse and brine shrimp
      (Artemia) bioassays. Apart from the sample collected on 15/06/1999, all the other
      samples were toxic by mouse bioassay. The LD50 determined by intraperitoneal
      injection to mice during active cyanobacterial growth and decline phases were 518
      and 1924 mgDW/kg respectively. Using Artemia bioassay, the 24hLC50 varied from
      6.0 to 40.6 mg/ml and the 48hLC50 ranged from 2.8 to 18.2 mg/ml. The separation
      and identification of microcystin variants was performed by high performance
      liquid chromatography-photodiode array detection. Eleven toxins were separated
      and preliminarily identified as microcystin variants as they exhibit a typical UV
      spectra like the microcystin-LR standard. The quantification of total
      microcystins determined by enzyme-linked immunosorbent assay showed that the
      contents were varied between 0.1 and 0.76 microgram/g DW.

PMID- 11847972
TI  - Detection and quantification of microcystins from cyanobacteria strains isolated
      from reservoirs and ponds in Morocco.
AB  - In Morocco, the occurrence of toxic cyanobacteria blooms is confirmed in some
      water bodies used for recreational and/or as drinking water reservoirs. According
      to WHO recommendations, the establishment of a monitoring program for
      microcystins is a necessity. This paper presents toxicological studies of 19
      toxic cyanobacteria strains of Microcystis, Synechocystis, Pseudanabaena, and
      Oscillatoria. These strains were isolated from various water bodies including
      natural lakes, reservoirs, and ponds located in central regions of Morocco. The
      isolation, culture, and biomass production of these strains was made on Z8 or
      BG13 media under laboratory controlled conditions. The hepatotoxicity of
      cyanobacterial lyophilized material was confirmed by mouse bioassays. The amount
      of microcystins produced by each strain was determined by the enzyme-linked
      immunosorbent assay (ELISA). The detection and identification of microcystin
      variants was performed by high performance liquid chromatography (HPLC) with
      photodiode array detection. Almost all strains showed medium to high toxicity,
      the estimated LD50 i.p. mice bioassay ranged between 28 to 350 mg/kg body weight.
      The concentrations of microcystins varied between 2.16 to 944 micrograms/g and
      26.8 to 1884 micrograms/g dry weight determined by ELISA and HPLC, respectively.
      The screening of bloom-forming and microcystin producer cyanobacteria strains in
      these fresh water bodies leads us to propose the need for the establishment of a
      survey of cyanobacteria and a cyanotoxin-monitoring program.

PMID- 11847973
TI  - Inhibition of sulfate-reducing bacteria by metal sulfide formation in
      bioremediation of acid mine drainage.
AB  - Acid mine drainage (AMD) containing high concentrations of sulfate and heavy
      metal ions can be treated by biological sulfate reduction. It has been reported
      that the effect of heavy metals on sulfate-reducing bacteria (SRB) can be
      stimulatory at lower concentrations and toxic/inhibitory at higher
      concentrations. The quantification of the toxic/inhibitory effect of dissolved
      heavy metals is critical for the design and operation of an effective AMD
      bioremediation process. Serum bottle and batch reactor studies on metal toxicity
      to SRB indicate that insoluble metal sulfides can inhibit the SRB activity as
      well. The mechanism of inhibition is postulated to be external to the bacterial
      cell. The experimental data indicate that the metal sulfides formed due to the
      reaction between the dissolved metal and biogenic sulfide act as barriers
      preventing the access of the reactants (sulfate, organic matter) to the necessary
      enzymes. Scanning electron micrographs of the SRB cultures exposed to copper and
      zinc provide supporting evidence for this hypothesis. The SRB cultures retained
      their ability to effect sulfate reduction indicating that the metal sulfides were
      not lethally toxic to the SRB. This phenomenon of metal sulfide inhibition of the
      SRB has to be taken into account while designing a sulfate-reducing bioreator,
      and subsequently an efficient biotreatment strategy for AMD. Any metal sulfide
      formed in the bioreactor needs to be removed immediately from the system to
      maintain the efficiency of the process of sulfate reduction.

PMID- 11847975
TI  - Potential genotoxicity of wastewater-contaminated pore waters with comparison to
      sediment toxicity and macrobenthic community composition.
AB  - The objectives of this survey were to determine the genotoxic potential of
      sediment pore waters above and below 10 wastewater outfalls and to compare the
      results to sediment chemical quality guidelines, acute toxicity, and macrobenthic
      community composition. The focus of the study was on genotoxicity since its
      occurrence in environmental media below wastewater discharges in the Gulf of
      Mexico region has not been reported in the scientific literature. Pore waters
      from 43 sediment samples were assayed using a microbial mutagenicity assay before
      and after activation with a rat liver microsome mix (S-9). A combination of
      either direct or activated responses was observed for 40% of the pore waters.
      Direct, activated, and both direct and activated responses were observed in 5,
      26, and 9% of the total samples, respectively. Mutagenic effects were observed
      below 7 of the 10 outfall areas and in 4 of 6 control areas associated with 6
      outfalls. The lowest pore water concentrations causing an activated mutagenic
      response were statistically similar above and below the outfalls. Mutagenicity
      occurred more frequently than acute toxicity to estuarine and freshwater
      invertebrates and there was no consistent relationship between its occurrence and
      the exceedance of sediment chemical quality guidelines. In contrast, there was
      some indication that mutagenic activity paralleled low benthic community
      diversity.

PMID- 11847974
TI  - The fate of diesel hydrocarbons in soils and their effect on the germination of
      perennial ryegrass.
AB  - Hydrocarbon contamination in soils may be toxic to plants and soil microorganisms
      and act as a source of groundwater contamination. The objective of this study was
      to evaluate the fate of diesel in soils with or without added nutrients. The
      soils examined either had or had not a previous history of hydrocarbon
      contamination. Particular aspects examined were soil respiration, changes in
      microbial population, breakdown of diesel hydrocarbons, and phytotoxicity to the
      germination of perennial ryegrass. Soil respiration was measured as evolved CO2.
      Bacterial population was determined as colony forming units in dilution plates
      and fungal activity was measured as hyphal length. The fate of individual
      hydrocarbons was determined by gas chromatography-mass spectrometry after
      extraction with dichloromethane. When diesel was added to soil with no previous
      history of hydrocarbon contamination at rates up to 50 mg/g, the respiration
      response showed a lag phase of 6 days and maximum respiration occurred at day 11.
      The lag phase was 2 days and maximum respiration occurred at day 3 in soil with a
      previous history of hydrocarbon contamination. After the peak, respiration
      decreased up to about 20 days in both soils. Thereafter, respiration become more
      or less constant but substantially greater than the control. N and P addition
      along with diesel did not reduce the lag phase but increased the respiration over
      the first 20 days of incubation. Diesel addition with or without N and P
      increased the bacterial population 10- to 100-fold but fungal hyphal length did
      not increase. Diesel addition at a rate of 136 mg/g did not increase the
      microbial population. Removal of inhibition to germination of perennial ryegrass
      was linked to the decomposition of nC10 and nC11 hydrocarbons and took from 11 to
      30 days at diesel additions up to 50 mg/g depending on the soil. Inhibition to
      germination of perennial ryegrass persisted to more than 24 weeks at the 136 mg/g
      of diesel addition.

PMID- 11847976
TI  - Comparison of 35 electronic databases for environmental risk assessment.
AB  - The objective of this work is to classify and evaluate the major factual
      electronic databases that could be efficiently questioned for environmental risk
      assessment of various chemicals. A series of 35 databases available on commercial
      CD-ROMs and/or freely accessible on the Internet were listed and compared for the
      presence or absence of information for 27 environmental criteria. A factorial
      correspondence analysis indicated that most of the 35 databases are specialized
      in physicochemical, toxicological or ecotoxicological data but a few of them are
      nonspecialized databases able to answer simultaneously in various areas. We then
      evaluated these 35 databases by querying them for 14 selected test chemicals. It
      appeared that the percentage of chemicals being listed in the databases was very
      unequal and none of the 35 databases obtained 14 positive responses. The quality
      of the responses was determined by calculating the number of criteria being
      documented for the previously listed chemicals in each database. It suggested
      that HSDB, DOSE, TOMES, IPCS are the most efficient databases to be used for an
      urgent search of environmental data.

PMID- 11847978
TI  - Acute toxicity, mutagenicity, and estrogenicity of bisphenol-A and other
      bisphenols.
AB  - Although abundant data are available on the toxicity of bisphenol-A (2,2-bis (4
      hydroxydiphenyl)propane; BPA), little is known about the toxicities of the
      structurally similar compounds, namely bisphenols (BPs). A variety of BPs were
      examined for their acute toxicity against Daphnia magna, mutagenicity, and
      estrogenic activity using the Daphtoxkit (Creasel Ltd.), the umu test system, and
      the yeast two-hybrid system, respectively, in comparison with BPA. BPA was
      moderately toxic to D. magna (48-h EC50 was 10 mg/l) according to the current
      U.S. EPA acute toxicity evaluation standard, and it was weakly estrogenic with 5
      orders of magnitude lower activity than that of the natural estrogen 17 beta
      estradiol in the yeast screen, while no mutagenicity was observed. All seven BPs
      tested here showed moderate to slight acute toxicity, no mutagenicity, and weak
      estrogenic activity as well as BPA. Some of the BPs showed considerably higher
      estrogenic activity than BPA, and others exhibited much lower activity. Among the
      tested BPs, two compounds, i.e., bisphenol-S (bis(4-hydroxydiphenyl)sulfone) and
      bis(4-hydroxyphenyl)sulfide, have never been reported for their estrogenic
      activity previously.

PMID- 11847977
TI  - Ecotoxicological monitoring of remediation in a coke oven soil.
AB  - Assessment of contaminated sites is usually based on chemical analyses of
      hazardous compounds in soil. This is enough either to assess the environmental
      hazard of contaminated soil nor to evaluate the efficiency of applied remediation
      techniques. Information on the bioavailability of complex mixtures of xenobiotics
      and degradation products cannot be provided by chemical analytical data, but
      results from bioassays can integrate the effects of pollutants in mixtures. In
      the preservation of human health and environmental quality, it is important to
      evaluate ecotoxicological effects of contaminated industrial soils to complement
      the techniques of analytical chemistry. The monitoring of a coke oven soil and
      the evaluation of the landfarming treatment technique, conducted on-site in a
      pilot scale installation, was done by a battery of ecotoxicological tests: acute,
      chronic, and genotoxicity tests. Contaminated soil samples revealed toxic effects
      for different species mainly due to high concentrations of polycyclic aromatic
      hydrocarbons (PAHs). After landfarming treatment, soil samples presented
      significant reduction in toxicity, confirming the effectiveness of the
      landfarming process pointed out by a significant reduction in low molecular
      weight PAH concentrations. Comparative analysis of the different ecotoxicological
      tests allowed the establishment and validation of a more suitable procedure for
      the monitoring of PAH contaminated soils.

PMID- 11847979
TI  - MFO induction potential of fish species native to the Swan-Canning Estuary,
      Western Australia.
AB  - The use of mixed function oxygenase (MFO) enzymes as a potential biomarker of
      pollution in the Swan-Canning Estuary was investigated in four indigenous fish
      species, Perth herring (Nematalosa vlaminghi), sea mullet (Mugil cephalus),
      yellowtail trumpeter (Amniataba caudavittata), and black bream (Acanthopagrus
      butcheri). Each experimental fish was intraperitoneally injected with 10
      micrograms/kg of 3,3',4,4',5-pentachlorobiphenyl per kilogram of fish using corn
      oil as a carrier. Controls were injected with 1 mL corn oil per kilo. Induction
      of the hepatic ethoxyresorufin-O-deethylase (EROD) activity was measured 10 days
      post injection. Perth herring did not survive the experimental period due to the
      poor ability of this fish to endure captivity and handling. Yellowtail trumpeter
      demonstrated a low EROD induction response (2-fold relative to controls), while
      sea mullet displayed a moderate EROD induction potential (3.5-fold relative to
      controls). Because of their lower EROD induction potential, yellowtail trumpeter
      and sea mullet were not considered the most suitable bioindicator species for
      Western Australian estuarine waters. Black bream has desirable population traits
      and had a relatively high MFO induction potential response (9-fold relative to
      controls). From the results it was concluded that, when using EROD induction as a
      biomarker, black bream is a suitable fish to use as a bioindicator species for
      investigations into the health of the Swan-Canning Estuary.

PMID- 11847980
TI  - Special issue: cross-cultural determinants of infant-feeding practices, Part 1.

PMID- 11847981
TI  - The state of the Innocenti Declaration targets in Italy.
AB  - If Italy is to meet the operational targets of the Innocenti Declaration, there
      will need to be changes in the way that breastfeeding is not only promoted but
      also protected and supported. During the celebration of World Breastfeeding Week
      in October 2000, a resolution was passed in the parliamentary Commissione per
      l'infanzia (Commission on Childhood) that committed the government to promoting,
      protecting, and supporting breastfeeding in a more active manner; to including
      breastfeeding as a health indicator; and to establishing national and regional
      goals for breastfeeding prevalence and duration. A next step that must be taken
      by the government is that of creating a national committee to coordinate the
      work. Progress toward accrediting a baby-friendly hospital needs to continue and
      must use the international standards as criteria. Recent action taken by the
      Ministry of Health and the court system is promising; however, full compliance of
      the International Code of Marketing of Breast-Milk Substitutes should be a goal
      for Italy and the rest of the European Union. The one area in which Italy seems
      to have fulfilled all of its obligations is the one concerning "imaginative
      legislation"; however, this shows that although legislative protection is
      important, it is not enough to ensure breastfeeding success.

PMID- 11847982
TI  - Responses to "An open letter to the WIC Program: the time has come to commit to
      breastfeeding".

PMID- 11847984
TI  - Breastfeeding support in the workplace.

PMID- 11847983
TI  - Responses to "An open letter to the WIC Program: the time has come to commit to
      breastfeeding".

PMID- 11847985
TI  - Sensory integration difficulties.

PMID- 11847986
TI  - The Ontario Mother and Infant Survey: breastfeeding outcomes.
AB  - A cross-sectional survey of postpartum women following discharge from five
      hospitals in Ontario, Canada, examined breatfeeding patterns and risk factors for
      early discontinuation. Consenting mothers completed self-administered
      questionnaires prior to discharge (n = 1250) and telephone interviews at 4 weeks
      postdischarge (n = 875). Breastfeeding initiation rates for women completing the
      interview varied from 82% to 96% across the sites. Continuation rates rapidly
      declined, with 13% to 24% of women who had initiated breastfeeding switching to
      formula by 4 weeks postpartum. Perceived inadequate milk supply, difficulty with
      breastfeeding techniques, and sore nipples were the main reasons reported. Risk
      factors for breastfeeding cessation included not completing high school;
      intention to breastfeed less than 4 months; not anticipating the use of a "mom's
      group" or "drop-in center"; one or more maternal visits to a family physician;
      length of postpartum stay greater than 48 hours; unmet need for care or help with
      breastfeeding; and received advice, information, or support about formula
      feeding.

PMID- 11847987
TI  - Factors influencing the duration of exclusive breastfeeding in a group of Turkish
      women.
AB  - This study was conducted to evaluate the influence of demographic
      characteristics, hospital practices, maternal psychosocial factors, and knowledge
      about infant feeding and breast milk on duration of breastfeeding. The mothers of
      91 healthy, term infants delivered at a university hospital between June 1998 and
      December 1998, and first seen in the well-child unit within 10 days of delivery,
      participated in the study. Forty-nine (54%) infants were exclusively breastfed at
      4 months of age. Cox regression analysis showed a negative association between
      formula supplementation during the hospital stay and duration of exclusive
      breastfeeding. The median age for starting non-breast milk liquids was 1 month
      for those who received formula in the hospital and 3 months for those who did not
      (P = .001). The hospital practices were more predictive of the duration of
      exclusive breastfeeding in this study group than mothers' knowledge of infant
      feeding or psychosocial factors. Thus, hospital practices should be reevaluated.

PMID- 11847988
TI  - Use of an intensity ratio to describe breastfeeding exclusivity in a national
      sample.
AB  - Breastfeeding behavior in a sample of 1863 mother-infant pairs was examined using
      data from the 1988 National Maternal-Infant Health Survey. Breastfeeding behavior
      was operationalized as an intensity ratio, calculated as the number of breast
      milk feeds (on average in 24 hours) divided by the total number of all liquid
      feeds (on average in 24 hours), with a range from 0 to 1.0. During the first
      month postpartum, 61% of the sample reported exclusive breastfeeding, declining
      to 31% during months 2-3 postpartum and to 13% during months 4-6 postpartum. This
      decline was consistent with the linear decline in the mean intensity ratio, .82,
      .55, and .31, respectively, during the same three time periods. A higher
      breastfeeding intensity ratio was significantly associated with longer duration
      of breastfeeding, up to 1 year of life. Intensity ratio, as a measure of
      exclusivity, is a useful outcome measure for monitoring breastfeeding behavior.

PMID- 11847989
TI  - Weaning, complementary feeding, and maternal decision making in a rural east
      African pastoral population.
AB  - A small-scale, prospective study of breastfeeding and weaning practices was
      conducted in a seminomadic pastoral population in northern Tanzania (Datoga of
      Mbulu District, Arusha Region). Focus group participants suggested that weaning
      patterns are strongly influenced by seasonal factors, and individual mothers
      often stated an intention to introduce adult staple foods and terminate
      breastfeeding at the end of the long rains. However, a combination of maternal
      self-perception, assessment of infant well-being, and indicators of household
      food supply influenced the actual progression of weaning for individual children.
      The results suggest that interventions to promote exclusive breastfeeding and
      improve complementary feeding practices in rural East African pastoral
      populations could build on maternal attention to infant-centered cues and address
      household-level constraints on caregivers making decisions about young child
      feeding.

PMID- 11847990
TI  - The effect of breastfeeding education on adolescent beliefs and attitudes: a
      randomized school intervention in the Canadian Ojibwa community of Sagkeeng.
AB  - Sagkeeng First Nation's adolescent breastfeeding educational session was
      evaluated using a randomized pretest-posttest control group design. The
      intervention group received the session first; the control group received the
      session following the posttest. A retention test to measure overall retained
      learning was given to all students 10 days later. Breastfeeding beliefs increased
      (mean +/- SD = 41.9 to 47.0, P = .0047) from pretest to posttest for intervention
      subjects but not for controls. There were no changes in bottle-feeding beliefs or
      breastfeeding attitudes. There was an increase in breastfeeding beliefs from
      pretest to retention test for all students (true treatment effect [TTE] = .85
      standard deviation units [SDU], P = .004). Learning was gender specific, with
      females experiencing increases in breastfeeding beliefs (TTE = 1.12 SDU, P =
      .004), decreases in bottle-feeding beliefs (TTE = -.77 SDU, P = .04), and a trend
      to increased breastfeeding attitudes (TTE = .41 SDU, NS). Males showed small,
      inconsistent learning effects. Learning occurred in the areas of health,
      convenience, cost, and decreased embarrassment.

PMID- 11847991
TI  - Antidepressant use during lactation.
AB  - Depression commonly affects women, particularly during their childbearing years.
      Often, pharmacologic therapy is the recommended treatment. Today, medication
      selection generally involves the newer antidepressants, with tricyclic
      antidepressant and monoamine oxidase inhibitors reserved for more refractory
      patients. Although there is ample evidence to support the benefits of
      breastfeeding in the infant, the scientific literature contains little
      information with regard to the transfer of antidepressants from the plasma into
      breast milk and the subsequent effects on the developing infant. Secondary to
      this lack of safety data, many clinicians and mothers are reluctant to breastfeed
      during antidepressant treatment. This article will review the literature for
      reports of the newer antidepressants' use during lactation.

PMID- 11847992
TI  - Taking it to the streets.

PMID- 11847993
TI  - Defining the severity of workplace violent events among medical and non-medical
      samples. A pilot study.
AB  - The purpose of this study was to describe and compare medical and non-medical
      individuals' violence severity rank for 13 commonly cited events illustrative of
      workplace violence. One hundred thirty-six college students were provided a short
      checklist of 13 violent events in the workplace to determine the violence
      severity rank for each event. Two groups of college students with (n = 69) and
      without (n = 67) medical background participated. Student and registered nurses
      (medical group) agreed on the violence severity ranking of all 13 often-cited
      workplace violence events. Non-medical and medical groups, however, did not
      always agree on the degree of violence severity, especially for physical and
      sexual workplace violence events. Differences between groups may be explained by
      the possibility that nurses are socialized or desensitized in practice to
      possibly accept some workplace violence events as "part of the job."
      Gastroenterology nurses can benefit from this study by raising their sensitivity
      to and awareness of workplace violence in the practice setting.

PMID- 11847994
TI  - Care of the laparoscopic Nissen fundoplication patient.
AB  - Gastroesophageal reflux disease can usually be successfully managed with
      conservative medical treatment. Anti-reflux surgery is a safe alternative when
      treatment fails or patients desire a more definitive treatment option. Through a
      case study approach, this article describes the indications for surgery, the
      essentials of the authors' multi-disciplinary approach to care and the components
      of a well-designed education plan for a patient undergoing laparoscopic Nissen
      fundoplication. Although most patients do well after surgery, diligent nursing
      care is required before and after surgery to prevent or manage complications and
      ensure patients have a rapid recovery and successful outcome.

PMID- 11847995
TI  - The advanced practice nurse in gastroenterology. Identifying and comparing care
      interactions of nurse practitioners and clinical nurse specialists.
AB  - Collaborative practice models using advanced practice nurses have been developed
      to provide high-quality healthcare in a cost-effective manner. Studies in
      gastroenterology nursing evaluating effectiveness of advanced practice nurses
      have been limited to performance of procedures, such as screening flexible
      sigmoidoscopies, and assisting with percutaneous endoscopic gastrostomy tube
      placement. Research and literature discussing the potential benefits of using
      advanced practice nurses as providers of care in a gastroenterology setting is
      limited. This cross-sectional descriptive study (N = 32) compares the nurse
      practitioner and clinical nurse specialist roles in gastroenterology.

PMID- 11847996
TI  - Diet triggers symptoms in women with irritable bowel syndrome. The patient's
      perspective.
AB  - The purpose of this phenomenological analysis was to describe perceptions of
      women with irritable bowel syndrome regarding the relationship of diet to their
      symptoms. Thirty-five women ages 18-45 with a medical diagnosis of irritable
      bowel syndrome or symptoms compatible with a diagnosis of irritable bowel
      syndrome were interviewed and completed questionnaires as part of a larger study.
      During the interview, the women were asked what they thought caused their
      symptoms. Overall, women tried to adjust their diet to achieve a "Range of
      Comfort" so their symptoms were tolerable or manageable. To do this, women used a
      process of "Trial and Error." If a link could be made to diet, then women
      developed "Self-care Strategies" to maintain a "Healthy Diet." Women who failed
      to find a relationship during the "Trial and Error" process either felt the
      frustration of "Uncertainty" or, for a few women, decided that adjusting their
      diet was not worth the bother. This study suggests diet and eating behaviors are
      an important starting point for many women as they try to manage their irritable
      bowel syndrome symptoms.

PMID- 11847997
TI  - Current instrument reprocessing practices. Results of a national survey.
AB  - In June 1998, a questionnaire was mailed to approximately 2,900 healthcare
      professionals to assess current instrument reprocessing and infection control
      practices and determine whether they have changed during the past decade. Surveys
      were returned from 146 respondents whose facilities performed gastrointestinal
      endoscopy. Most respondents were registered nurses and almost all worked in
      healthcare facilities located in the United States. More than 75% of the
      respondents reported that infection control practices in endoscopy have improved
      during the past 10 years. Most respondents used glutaraldehyde to reprocess
      flexible endoscopes. Immersing endoscopes for 20 minutes at room temperature was
      commonly practiced. Almost 75% of respondents used an automated device to
      reprocess flexible endoscopes. Most respondents terminally rinsed the endoscope's
      channels with 70% alcohol followed by forced-air drying. Few respondents
      outsourced instruments to a commercial reprocessing company and almost 50% reused
      disposable items. While some practices in endoscope reprocessing have changed
      during the past several years, others have not. In general, infection controls
      appear to have improved during the past decade, with the possible exception of a
      trend to reuse single-use items.

PMID- 11847998
TI  - Stress management. The complementary alternative medicine approach.

PMID- 11847999
TI  - The leader's role in stopping the bugs.

PMID- 11848000
TI  - Chronic hepatitis C. Implications for health-related quality of life.
AB  - Hepatitis C viral infection with its sequelae is a significant healthcare
      problem. Hepatitis C infects nearly 4 million Americans with almost half of these
      unaware of their infection. Many of those individuals infected with hepatitis C
      develop chronic hepatitis C and in 15% of these patients, the infection will
      progress to cirrhosis within 20 years. Several cross-sectional and longitudinal
      studies have demonstrated the negative impact of chronic hepatitis C on health
      related quality of life. This review describes what is currently known about the
      impact of chronic hepatitis C on health-related quality of life during
      pharmacologic treatment and after liver transplantation. It is important to note
      that few studies have prospectively followed patients over time with respect to
      quality of life or examined other factors including symptoms, markers of disease
      progression, or host immune function. Studies suggest that patients with chronic
      hepatitis C, even without major disease-related complications, perceive
      themselves to be unwell and have significant changes in their physical and mental
      well being. Such results have important implications for nursing care and
      management. Intervention studies focused on self-care management with an emphasis
      on symptom reduction are warranted.

PMID- 11848001
TI  - Comparison of three forms of bowel preparations for screening flexible
      sigmoidoscopy.
AB  - Our initial attempts at implementing a high-volume clinic were impeded by the
      quality of colon preparation. While two Fleet enema preparations were generally
      easy to administer and well tolerated, the results were frequently poor. Current
      studies are limited and opinions vary regarding the most effective bowel
      preparation. The purpose of this study was to compare three forms of bowel
      preparation for screening flexible sigmoidoscopy. All patients scheduled for
      screening flexible sigmoidoscopy were given one of three colon preparations: two
      Fleet enemas; magnesium citrate orally the evening before, clear liquid diet and
      two Dulcolax suppositories the day of the exam; or magnesium citrate orally the
      evening before, clear liquid the day of the exam, and two Fleet enemas 1 hour
      before the procedure. Examinations were performed using a video flexible
      sigmoidoscopy by specialty trained gastroenterologists. Physicians were asked to
      rate the preparations as excellent, good, fair, or poor according to explicit
      criteria, and to document depth of insertion. Results showed that the magnesium
      citrate and Fleet enema preparation was excellent for 70% of patients, allowing
      for greater depth of insertion. Need for repeat examination due to poor
      preparation was infrequent with this group and patient tolerance of the
      preparation was acceptable.

PMID- 11848002
TI  - Clinical decision making by nurses when faced with third-space fluid shift. How
      well do they fare?
AB  - Nurses' use of knowledge, the connection of this knowledge to treatment decisions
      and information actually used to reach such decisions, delineates nurses' level
      of expertise. Previous research has shown that nurses in their clinical decision
      making use the hypothetico-deductive method and intuitive judgment or pattern
      recognition. This interpretive study explored experienced critical care nurses'
      (n = 5) and gastrointestinal surgical nurses' (n = 5) clinical decision-making
      processes through ascertaining their knowledge and understanding of third-space
      fluid shift in elderly patients undergoing major gastrointestinal surgery. Both
      groups of nurses, because of their experience with elderly patients undergoing
      gastrointestinal surgery, were assumed to be experts. Data collection techniques
      included semi-structured interviews and the use of think aloud protocol for
      clinical scenario analysis. The findings demonstrated that the gastrointestinal
      surgical nurses used the hypothetico-deductive method to recognize critical cues
      and the existence of a problem but could not name the problem. The critical care
      nurses, on the other hand, used a combination of the hypothetico-deductive method
      and pattern recognition as a basis for identification of critical cues. The
      critical care nurses also possessed in depth knowledge of third-space fluid shift
      and were able to use pivotal cues to identify the actual phenomenon. Ultimately,
      it would appear that the structure of critical care nurses' work, their increased
      educational qualifications and the culture of the critical care unit promote a
      more proactive approach to reasoning in the physiological domain. The findings
      have implications for the development of practice guidelines and curriculum
      development in both tertiary and continuing nurse education.

PMID- 11848004
TI  - Standards of clinical nursing practice: performance and standards of care for the
      gastroenterology and/or endoscopy setting.

PMID- 11848003
TI  - Assessment of side effects in patients with chronic hepatitis C receiving
      combination therapy.
AB  - The purpose of this descriptive study is to review the adverse effects of
      combination therapy, interferon alfa-2b and ribavirin, in a sample of patients
      with chronic hepatitis C who were part of a larger multi-center trial (Bonkovsky,
      1999). The sample (n = 13) was drawn from one hepatology practice in the
      northeastern United States. This secondary analysis reported sums, frequencies,
      means, and standard deviations for the sample. Patients who received 600 mg
      ribavirin per day in addition to interferon alfa-2B (Arm A) showed a mean of 9.5
      different types of side effects. Patients who received 1000-1200 mg of ribavirin
      in addition to interferon alfa-2B (Arm B) had a mean of 8.6 different types of
      side effects. The highest-ranking side effects were fatigue (92%), insomnia
      (85%), alopecia (69%), and arthralgia (62%). A secondary analysis of the entire
      data set is required before confidence can be placed in the findings.
      Implications for nursing practice include the need for creative strategies to
      reduce the effects of fatigue, insomnia, alopecia, and arthralgia in patients
      with chronic hepatitis C.

PMID- 11848005
TI  - Role delineation of the registered nurse in a staff position in gastroenterology.

PMID- 11848006
TI  - Role delineation of the licensed practical/vocational nurse in gastroenterology.

PMID- 11848007
TI  - Role delineation of unlicensed assistive personnel in gastroenterology.

PMID- 11848008
TI  - Role delineation of the advanced practice nurse in gastroenterology.

PMID- 11848009
TI  - Safety of herbal remedies.

PMID- 11848010
TI  - [Management in premature rupture of the membranes (PROM) at term--own
      experiences].
AB  - In our study the management and outcomes in 211 women with premature rupture of
      the membranes at term was analyzed. According to the time elapsed since PROM to
      delivery the study group was divided into four groups: within 6 h, within 6-12 h,
      within 12-24 h and over 24 h after PROM. The analysis was focused on the maternal
      age, obstetric history, induction of labor, mode of delivery, duration of
      interval between PROM and active labor, use of maternal antibiotics, newborns
      evaluation in Apgar score and the neonatal infections. CONCLUSIONS: 1. In our
      study PROM at term occurred more frequently in primigravidae than in
      multigravidae. 2. The relationship between duration of time from the membranes
      rupture to delivery and frequency of labor induction, use of maternal antibiotics
      and neonatal infections was observed. 3. The higher percentage of cesarean
      sections in patients with interval from PROM to delivery less than 6 and over 24
      hours was found.

PMID- 11848012
TI  - [Qualitative blood flow parameters in the spiral artery and progesterone
      concentration in pregnancy complicated by threatened abortion].
AB  - OBJECTIVES: The aim of the study was to determine the values of i.e. resistance
      index (RI) and pulsatility index (PI) in the spiral arteries and to evaluate the
      maternal serum concentration of progesterone trying to find correlation between
      these parameters in the group of patients in early pregnancy complicated by
      threatened abortion. STUDY METHODS: We have analysed 30 pregnant women between
      5th and 12th weeks of pregnancy with the symptoms of vaginal bleeding & lower
      abdominal pains diagnosed as threatened abortion. In all patients transvaginal
      ultrasound examination with pulse color Doppler was performed. The RI and PI
      values were calculated for blood flow velocity waveforms obtained from the spiral
      arteries. The concentration of progesterone in maternal serum was evaluated by
      Microparticle Enzyme Immunoassay. The correlation between analysed parameters and
      pregnancy duration was examined with use of linear correlation by Pearson. The
      correlation between Doppler and biochemical parameters were analysed with use of
      rang correlation method by Spearman. RESULTS: Thirty flow velocity waveforms from
      spiral arteries were analysed and blood flow indices were calculated. We have
      found statistically significant negative correlation between the values of both
      blood flow parameters (RI & PI) and successive weeks of pregnancy (p < 0.001) and
      statistically significant positive correlation between maternal serum
      concentration of progesterone and pregnancy duration (p < 0.05). In the tested
      group in 40% of patients the level of progesterone was abnormal. We have not find
      any correlation between serum progesterone concentration and doppler parameters
      in our study. CONCLUSIONS: There is observed the characteristic drop of
      resistance to the blood flow in the vessels of the uteroplacental circulation in
      the successive weeks of early pregnancy in patients with threatened abortion
      similar to normal early pregnancies. Lack of correlation between maternal serum
      concentration of progesterone and blood flow parameters indicates that other
      hormonal factors play major role in the regulation of the blood flow in these
      vessels in early pregnancy. Only the combination of Doppler blood flow analysis
      in spiral arteries and progesterone evaluation in the maternal serum performed in
      first trimester may be useful for the intensive fetal monitoring of high risk
      pregnancies.

PMID- 11848011
TI  - [The influence of chosen hormones on lipids and its correlation during normal
      pregnancy].
AB  - OBJECTIVES: Lipids and hormones levels in nonpregnant and pregnant with
      uneventful gestation (from I, II, III trimester) were estimated and its
      correlation was evaluated. METHODS: The study group consisted of 219 women: 49
      nonpregnant and 170 pregnant women (35 in I trimester, 35 in II and 100 in III
      trimester of gestation). All subjects were healthy. Following parameters were
      measured in blood serum: total lipids, LDL total fraction, (beta-lipoproteids),
      cholesterol both total and free, HDL cholesterol, LDL cholesterol. Percentage of
      free cholesterol contained on total cholesterol was evaluated. HPL and estrogens
      levels were estimated. RESULTS: Serum levels of total lipids, phosphlipids,
      triglicerides, total fraction of LDL and its contains of cholesterol increase
      with gestational age (p < 0.001). During pregnancy positive correlation between
      estrogens, HPL and triglycerides was also observed (p < 0.001). Additionally in
      II trimester positive correlation of total cholesterol, phospholipids and HPL was
      noted (respectively r = 0.469 p < 0.001 and r = 0.452 p < 0.01). CONCLUSIONS: In
      case of women with uneventful pregnancy positive correlation between estrogens
      and total lipids, total fractions LDL and triglycerides was stated. Also positive
      correlation among lipids parameters and HPL concentration was noted. No
      correlation between HPL and free cholesterol, LDL, HDL cholesterol nor between
      estrogens and total cholesterol, free cholesterol and LDL cholesterol was found.
      Lipids status in case of nonpregnant women is multihormonaly influenced.

PMID- 11848013
TI  - [Transvaginal sonography in prediction of preterm delivery in patients presenting
      with signs and symptoms of preterm labor].
AB  - OBJECTIVE: The purpose of the study was to assess the clinical value of
      transvaginal sonography in the group of women presenting with preterm
      contractions and cervical changes. MATERIAL AND METHODS: We prospectively
      evaluated 82 patients between 23-34 weeks of gestation presenting in our
      department with signs and symptoms of preterm labor, intact membranes and
      cervical dilatation < 3 cm. In all cases transvaginal sonography was performed.
      The following parameters were assessed: functional canal length, funneling,
      cervical diameter and the length of the vaginal portion of the cervix. The
      primary outcome was delivery < or = 28 days from examination. RESULTS: The rate
      of preterm delivery (< 37 weeks) was 25.6% (21/82) and 17.1% (14/82) of the
      patients delivered < or = 28 days from the examination. Among the analyzed
      parameters, the significant difference between patients delivered < or = 28 and >
      28 days from examination, was noticed only for the functional canal length (21.6
      mm vs 30.1 mm; p < 0.001). The analysis of ROC curves showed that functional
      canal length had the highest diagnostic capability. Two important thresholds were
      found--20 mm and 31 mm. For predicting delivery < or = 28 days the functional
      canal length < or = 20 mm had sensitivity of 57.1%, specificity of 92.6%, PPV of
      61.5% and NPV of 91.3%. The cutoff value of 31 mm had sensitivity of 100%,
      specificity of 47.1%, PPV of 28% and NPV of 100%. In multiple logistic regression
      analysis only FCL < or = 20 mm (OR 8.18; p = 0.027) was independently associated
      with PTD. CONCLUSIONS: 1. The shortening of the functional canal length (< or =
      20 mm) is predictive of impending preterm delivery and the functional canal
      length > 31 mm is the indicator of the absence of labor. 2. Cervical sonography
      can be a valuable adjunct to the clinical assessment of patients with signs and
      symptoms of preterm labor.

PMID- 11848014
TI  - [Maternal plasma and amniotic fluid interleukin-6 and tumor necrosis factor-alpha
      levels in imminent preterm labor].
AB  - DESIGN: Our purpose was to investigate the maternal plasma and amniotic fluid
      interleukin-6 and tumor necrosis factor-alpha levels in women with imminent
      preterm labour. MATERIAL AND METHODS: The present study was designed to evaluate
      IL-6 and TNF-alpha levels in 93 pregnant women with threatened preterm labour and
      40 women with normal pregnancy. Maternal blood samples were collected by routine
      forearm venipuncture at admission during routine laboratory tests. Amniotic fluid
      was collected through hysterectomy during caesarean delivery from women at term
      but not in labour and by amniotomy or hysterectomy from women with preterm
      labour. RESULTS: Maternal plasma and amniotic fluid IL-6 and TNF-alpha
      concentrations were significantly elevated in women with preterm labour
      (premature rupture of membranes and uterine contractions) compared to
      gestationally matched, non-labouring controls.

PMID- 11848015
TI  - [Diagnostic values of lactate dehydrogenase (LDH), creatine kinase (CK) and gamma
      glutamyltransferase (gamma-GT) examinations in the course of intrahepatic
      cholestasis in pregnancy].
AB  - OBJECTIVE: The activity of LDH, CK and gamma-GT in blood serum of women with
      intrahepatic cholestasis in pregnancy was investigated. Diagnosis of intrahepatic
      cholestasis was based on anamnesis, clinical examination and laboratory tests.
      METHODS: 41 women with intrahepatic cholestasis (the study group) and 30 healthy
      women (the control group) entered the study. All women were in the third
      trimester of pregnancy. The prevalence rate of intrahepatic cholestasis in
      pregnancy in our Department is 1%. All women of the study group presented an
      intensive pruritus and had negative hepatitis B antigen. They also presented
      negative results of laboratory tests, clinical examination and anamnesis
      concerning other hepatitis. RESULTS: There was no significant difference in mean
      gestational age between study and control group (35.1 +/- 2.8 vs 36.0 +/- 3.0
      weeks). The results of biochemical tests in study vs control group: 1) total
      bilirubin 33.3 +/- 18.8 vs 8.55 +/- 3.4 mumol/L; p < 0.001, 2) direct bilirubin
      25.6 +/- 14.2 vs 1.7 +/- 1.7 mumol/L; p < 0.001, 3) indirect bilirubin 7.7 +/-
      2.22 vs 8.5 +/- 3.4 mumol/L; NS, 4) alkaline phosphatase (AP) 168.4 +/- 61.2 vs
      96.8 +/- 14.9 IU/L; p < 0.001, 5) heat-stable AP 99.8 +/- 38.7 vs 64.1 +/- 20.9
      IU/L; p < 0.001, 6) bile acid 28.6 +/- 20.0 vs 4.5 +/- 1.5 mumol/L; p < 0.001, 7)
      AlAT 158 +/- 00 vs 5 +/- 3 IU/L; p < 0.001, 8) AspAT 97 +/- 31 vs 8 +/- 3 IU/L; p
      < 0.001, 9) de Ritis ratio AspAT/AlAT 0.61 +/- 0.31 vs 1.6 +/- 0.4; p < 0.001,
      10) total protein 61.8 +/- 5.6 vs 66.0 +/- 6.0 G/L; p < 0.001, 11) albumine 450
      +/- 34.8 vs 484.0 +/- 37.7 mumol/L, 12) Fe++ 26.0 +/- 3.8 vs 12.71 +/- 2.15
      mumol/L; p < 0.001, 13) total cholesterol 8.81 +/- 1.87 vs 6.68 +/- 1.04 mmol/L;
      p < 0.001, total LDL 6.80 +/- 1.57 vs 4.80 +/- 0.81 G/L; p < 0.001, 15) LDH 211
      +/- 48 vs 134 +/- 33 UI/L; p < 0.001, 16) CK 51.0 +/- 33 vs 45 +/- 14 UI/L; NS,
      17) gamma-GT 49 +/- 22 vs 23 +/- 8 UI/L; p < 0.001. CONCLUSIONS: An increase of
      LDH is related to the significant impairment of hepatocytes. An increase of gamma
      GT confirms the retention of bile in intrahepatic ducts. CK does not present
      prognostic value in intrahepatic cholestasis in pregnancy.

PMID- 11848016
TI  - [Peripheral blood neutrophils reactive oxygen intermediates (ROI) production in
      early pregnancy complicated by diabetes mellitus type I].
AB  - The components of maternal innate immune system are activated in pregnancy.
      Increased number of circulating neutrophils and monocytes, reactive oxygen
      intermediate production (ROI), increased expression of the adhesion molecules can
      be observed. The activation status and neutrophils response to stimulators in
      pregnant diabetic women's comprise, to some extend, both situations pregnancy and
      diabetes, combined effect of both seems to be very intriguing. AIM OF STUDY:
      Evaluation production of ROI on peripheral blood neutrophils in early pregnancy
      of diabetic mothers. MATERIAL: 12 pregnant diabetic women demonstrating good
      glycemic control and without major complications before pregnancy were studied at
      8-12 weeks of first gestation, 11 healthy pregnant women match for weeks of
      gestation, age and parity; 11 healthy non-diabetic women; 13 diabetic, non
      pregnant women, were also studied. METHODS: ROI production was evaluated with
      chemiluminescence method using standard stimuli fMLP, PMA, OZ and also after 15
      min. priming with TNF-alpha. We used MLX Microtiter Plate Luminometr DYNEX, USA.
      with computer program Revelation 97. For statistic analysis Fisher, Kolmogorow
      Smirnow and Wilcoxon tests were used (p < 0.05). RESULTS: 1. Peripheral blood
      neutrophils of healthy pregnant, diabetic and pregnant diabetic women
      independently from the stimuli used showed an increase in ROI production 2.
      Peripheral blood neutrophils change their activity, evaluate by ROI production
      during pregnancy, diabetes and pregnancy complicated by diabetes. 3. Peripheral
      blood neutrophils of pregnant diabetes women do not show expected impairment of
      their function. CONCLUSIONS: Diabetes type 1 with good glycemic control and
      pregnancy, change the production of ROI by peripheral blood neutrophils but these
      events do not sum up in diabetic pregnancies.

PMID- 11848017
TI  - [Effect of ambroxol on lipid peroxidation in homogenates of the human placenta].
AB  - Free radically induced lipid peroxidation has been suggested as a possible
      pathogenic factor in pregnancy complications. The placenta is a potential source
      of lipid peroxides, due to its high lipid concentration. Cells and tissues are
      protected against toxic lipid peroxides by antioxidants. Ambroxol was found to be
      equipotent to well-known antioxidants in protecting lipids from peroxidative
      attack in lungs. To date there is no information on ambroxol capacity to act as a
      lipid antioxidant in the human placenta. Therefore, the aim of our study was to
      investigate the effect of ambroxol on lipid peroxidation in homogenates of the
      human placenta by malondialdehyde measurements. Fourteen homogenates of placentas
      obtained from healthy women were incubated for 24 hours (pH = 7.4, temp. 37
      degrees C) without (group II) and with (group III) ambroxol hydrochloride
      solutions (Boehringer Ingelheim--Germany) at concentration of 2200 ng/mL. Non
      incubated homogenates were treated as a control group (group I). It was found
      that lipid peroxidation and malondialdehyde formation is significantly higher in
      group II homogenates than in the control group (p < 0.05). Incubation with
      ambroxol (group III) caused a non-significant increase of malondialdehyde
      concentration in comparison with the control group and a non-significant but
      distinct decrease when compared with group II (incubation without ambroxol). This
      investigation shows that ambroxol decreases malondialdehyde formation in
      homogenates of the human placenta and can be regarded as lipid antioxidant.

PMID- 11848018
TI  - [Changes in mammography and breast ultrasonography in women undergoing hormonal
      replacement therapy].
AB  - OBJECTIVES: The aim of this study was to compare changes in mammography and
      breast ultrasonography in women undergoing Hormonal Replacement Therapy (HRT) and
      a control group. MATERIALS AND METHODS: Retrospective analysis of clinical
      documentation form 12.1998 to 11.1999 of 1075 women over 45 years old. COLLECTED
      DATA INCLUDED: Breast imaging, hormonal therapy, gynecological, obstetrical and
      oncological interview and examination. Analysis was performed using MS Access
      DataBase and Statistica v5.0, p = 0.05 was considered significant. RESULTS: 710
      women were actually undergoing HRT and 365 were qualified to the control group.
      Oral HRT was used by 72.2% women, transcutaneous by 24.1% and transvaginal by
      3.7%. There were no differences of breast cancer risk factors, age and cancer
      suspicious changes (relative risk 1.03) in analyzed groups. Suspicious
      microcalcifications were rarer in women undergoing HRT (relative risk 0.49) while
      breast cysts (especially to 0.5 cm) were more frequent. There were no
      statistically significant differences in other changes like: benign breast
      masses, macrocalcifications and mastopathy. All findings referred to
      superiolateral quadrant in 50% of HRT women and 56% of control group.
      CONCLUSIONS: Hormonal Replacement Therapy has no marked influence on changes in
      mammography and ultrasonography. Among women undergoing HRT, microcysts are more
      frequent while suspicious microcalcifications are less.

PMID- 11848019
TI  - [Influence of hormonal replacement therapy on bacterial vaginosis in the group of
      peri- and postmenopausal women].
AB  - The aim of the study was to evaluate microbiological biocenosis of the menopausal
      or postmenopausal women, and women having local hormonal therapy (Ovestin and
      Ortho-Gynest D). The study group consisted of 123 women (aged 45-72), who
      underwent clinical examination and microbiological evaluation of vaginal
      discharge. Miller's and Gramm's methods were used for slide staining and the
      culture method for growing microorganisms. Classical culture media were used as
      well as Rogosa culture medium and modified Weinstein medium for Lactobacillus
      culture in anaerobic conditions. In the microbiological studies before initiation
      of hormonal therapy, normal biocenosis of the vagina was found in 52 women
      (42.27%). The other part of the study group had abnormal vaginal biocenosis or
      had no microorganisms at all. During the hormonal therapy, the group of women
      with normal biocenosis increased to 53.65% and 62.29% after respectively 3 and 9
      months of therapy. Hormonal therapy secured continuity of normal Lactobacillus
      morphotypes within perimenopausal period. Antimicrobial and hormonal therapies
      used together provided normalization of vaginal biocenosis in a shorter time. In
      the group of senile women, the recolonization of vaginal mucosa by Lactobacillus
      vaginalis was observed.

PMID- 11848020
TI  - [Stromal leydig cell tumor coexisting with ascites].
AB  - The stromal Leydig cell tumour (SLCT), a very rare, benign neoplasm was described
      in 75-year old woman. The patient presented the typical signs of virilisation
      (hirsutism, masculine alopecia, moderate clitoris enlargement, deep voice) as
      well as hypertension and insulin independent type of diabetes mellitus (IIDM).
      Additionally, she had marked ascites (3400 ml as established during surgery). The
      serum concentration of testosterone before the surgery was elevated up to 7.6
      ng/ml. FSH and LH were at very low range (2.5 mIU/ml, 3.4 mIU/ml, respectively)
      whereas 17 beta-oestradiol was elevated (56 pg/ml). Total abdominal hysterectomy
      with salpingo-oophorectomy (TAH/BSO) and omentectomy were performed. The
      histopathological findings revealed stromal Leydig cell tumour with Reinke
      crystalloids. The postoperative follow-up was complicated by venous thrombosis.
      Five weeks after the surgery only slight regression of the signs of virilisation
      was observed. Hormonal findings were adequate to the patient age range (FSH--16.7
      mIU/ml, LH--21.1 mIU/ml, testosterone--0.19 ng/ml, 17 beta-oestradiol
      concentration below 10 pg/ml).

PMID- 11848023
TI  - [Intracytoplasmic sperm injection (ICSI): the Bialystok experience].
AB  - OBJECTIVE: To present a complete results of Intracytoplasmic Sperm Injection
      Program (ICSI) performed at IVF Unit in Bialystok, Poland. DESIGN: Retrospective
      data analysis. MATERIALS AND METHODS: A total of 2593 cycles of ICSI treatment
      were analyzed. The results of controlled ovarian hyperstimulation (COH),
      parameters of fertilization, early embryo development and clinical pregnancy
      rates were compared depending on the type of COH used. RESULTS: Overall, for
      16708 MII oocytes microinjected, the 2 pronuclear fertilization rate was 54%.
      Embryo transfer was performed in 94% of started cycles and 629 clinical
      pregnancies were recorded, giving a clinical pregnancy rate of 24% per cycle and
      26% per transfer. No influence of COH on embryological and clinical results was
      noted. CONCLUSION: Intracytoplasmic sperm injection can be used successfully to
      treat couples with male factor infertility and those who have failed standard
      IVF. Precisely adapted protocol of ovarian hyperstimulation for every patient
      could diminish the costs of treatment without negative influence on ICSI results.

PMID- 11848021
TI  - [Photodynamics in gynaecology].
AB  - Photodynamic procedures were intended for early detection and therapy of
      neoplastic diseases. Fluorescence diagnosis is based on the detection of the
      fluorescence of exo- and endogenous photosensitizers selectively accumulated in
      pathological tissues. Photodynamic therapy is based on the selective destruction
      of neoplastic tissue resulting from interaction between photosensitizer, light
      and oxygen. The main fields of the clinical use of photodynamics are pulmonology,
      gastroneterology, urology and dermatology. The article presents the theoretical
      principles of fluorescence diagnosis and photodynamic therapy followed by the
      review of up-to-date literature concerning the use of photodynamics in diseases
      of the genital tract in women.

PMID- 11848024
TI  - [Importance of cytogenetic analysis in patients with azoospermia or severe
      oligozoospermia undergoing in vitro fertilization].
AB  - The karyotypic analysis was performed to assess the importance of genetic factor
      in male infertility. For that purpose, chromosomal analysis in blood lymphocytes
      was performed in 28 males, candidates for ICSI with azoospermia or severe
      oligozoospermia and in their spouses. Although chromosomal aberrations were
      identified in as many as 11 couples, (in 6 couples aberrations were identified in
      male, in 4 other couples in female partner, whereas in 1 one couple they were
      detected in both partners) their risk for potential offspring is unequal.
      Balanced autosomal aberrations detected in two males (7%) constitute a high risk
      since they can cause not only infertility but also severe somatic abnormalities
      if transferred as the unbalanced ones to the next generation. The remaining 9
      chromosomal aberrations identified in this study were present in mosaic
      additional cell lines with low representation. In 8 of them sex chromosomes and
      in 1 an autosom were involved. Although these mosaic chromosomal aberrations can
      lower efficiency of in vitro fertilisation, the probability that they can be
      transferred to the next generation causing somatic abnormalities is not high.
      This study indicates that in case of azoospermia or severe oligozoospermia, the
      karyotypic analysis should be performed in both partners prior to in vitro
      fertilisation.

PMID- 11848025
TI  - [TPS and SCC antigens in diagnosis and monitoring treatment of patients with
      cervical cancer].
AB  - DESIGN: The purpose was to evaluate the usefulness of serum TPS and SCC assay for
      the monitoring radiotherapy of patients with cervical cancer. MATERIALS AND
      METHODS: 38 patients with cervical cancer treated with radiotherapy were included
      in this study. The concentrations of TPS and SCC were determined prior to
      radiotherapy, after radiotherapy, 3 and 6 months after radiotherapy. RESULTS: The
      increase in TPS levels prior to treatment was observed in serum of 80% women, SCC
      rose by 71%. The frequency of increased results and absolute value of TPS levels
      showed tendency to significant increase together with development of disease and
      degree of histological differentiation. A significant decrease of TPS and SCC
      level was observed during radiotherapy. The TPS levels decreased above cut-off
      values in all patients, SCC in 90% patients with remission after radiotherapy. In
      cases of patients who still had high TPS antigen level after treatment,
      progression of cancer was found. CONCLUSIONS: These results suggest that TPS and
      SCC are useful in monitoring treatment of patients with cervical cancer.

PMID- 11848026
TI  - [Results of treatment of vesicovaginal fistulas].
AB  - OBJECTIVES: The results of treatment of 74 patients with vesicovaginal fistulas
      are presented. MATERIALS AND METHODS: The clinical analysis have been performed
      in 74 women aged from 24 to 70 years (on average 53.4), who had to be treated for
      vesicovaginal fistulas in the Department of Urology of Lublin University School
      of Medicine between 1966-1999. RESULTS: The most common cause of vesicovaginal
      fistulas was gynaecological surgery. Patients who-underwent the operation 96, 9%
      were cured (after 1st operation 84, 8%). 8 cases were cured by using conservative
      therapy.

PMID- 11848027
TI  - [Vesico-uterine fistula].
AB  - Our observations of 14 women with vesico-uterine fistulas as a result of
      caesarean section complications were presented. The patients were treated between
      1965-1999 in urology clinic in Lublin. The case were diagnosed on the basis of
      medical history, radiological investigations and cystoscopy. In 3 cases
      hysterectomy was performed, in the rest of cases uterus was preserved and after
      the first operation complete recovery was observed.

PMID- 11848028
TI  - [The prognostic meaning of the selection parameters amniotic fluids samples and
      frequency occurrence respiratory distress newborn].
AB  - Prenatal diagnosis of amniotic fluid enables the evaluation of fetal lungs
      maturity. The aim of the study is to evaluate prognostic significance of
      measurement of concentration of lamellar body count (LC) in comparison with other
      laboratory investigations for prenatal fetal lung maturity evaluation. The study
      was carried out on 60 amniotic fluid collections obtained by amniocentesis of
      pregnant women, hospitalized in Polish Mother's Health Centre between August 1998
      January 2000. Following tests were performed: phosphatydyloglicerol concentration
      (PG), concentration of lamellar body (CLC), optical density-reading absorbance in
      wave length 400, 570, 650 nm. Test PG showed 70% specificity and 100%
      sensitivity, LC 70% specificity; 100% sensitivity. PG and LC showed good
      correlation for the assessment of fetal lung maturity. The study involved small
      number of patients pointed out the necessity of continuation quantitative
      investigation of LC to confirm diagnostics utility for the assessment of fetal
      lung maturity.

PMID- 11848030
TI  - [Acute complete uterine inversion--care report].
AB  - OBJECTIVES: Acute puerperal uterine inversion is a rare but very feared
      obstetrical complication. It determines an almost immediate shock and serious
      metrorrhagia. It is a introflexion of parietes uteri which takes place during the
      third stage of labor or during the first hours of puerperium. It can be
      distinguished in inversion of I, II or III degree according to the zone concerned
      by the introflexion: only the fundus of the uterus, all the corpus emerging in
      the vagina or the entirety of the uterus coming out from the vulvar orifice.
      RESULTS: This is report a case of inversion of the uterus during third stage of
      labor in multiparous aged 24 years admitted to Department of Gynecology &
      Obstetric in Hospital of Slupsk. The uterine III degree inversion was spontaneous
      during third stage of labor and was immediately diagnosed. Manual manipulation
      was attempted immediately to reverse the inversion but it was not successful.
      Because patient fell in cardiovascular shock she was resusciated and the inverted
      uterus repositioned using Huntington's method under general anaesthesia. After
      intra-abdominal repositioning of the uterus the placenta was removed manually and
      intramural injection of oxitocine was done to avoid immediate relapse. Whole
      obstetrical procedure was carried out within one-half hour after inversion.
      CONCLUSIONS: Although uncommon, in left unrecognized, uterine inversion will
      result in severe hemorrhage and shock, leading to maternal death. Manual
      manipulation should be attempted immediately to reverse the inversion. In the
      most resistant of inversions, surgical correction might be required. Following
      inversion of the uterus, further normal pregnancies can be expected.

PMID- 11848029
TI  - [Breus' mole in case of pregnancy in 22 years old primipara--a case report].
AB  - A case of massive subchorial thrombohaematoma during pregnancy in 22 years old
      primipara is presented. The idea was to prolonged pregnancy as possible to term
      of lung maturity. Became described manner of diagnosis, treatments and way of
      delivery in this rare case of pathology.

PMID- 11848031
TI  - [Recurrent spontaneous abortion of alloimmunologic etiology--diagnosis and
      immunotherapy].
AB  - Alloimmunologic mechanisms have been implicated in a number of heretofore
      unexplained recurrent spontaneous abortions (RSA) and various forms of
      immunotherapy have been introduced to treat couples suffering from this
      condition. The treatment most widely used has been immunization using allogenic
      leukocytes from the partner. This immunotherapy is offered by many medical
      centers in the USA and elsewhere, although its efficacy remains controversial.
      Published trials and meta-analyses of published and unpublished studies have
      yielded conflicting results (success rate 57%-87%). The multicenter study
      performed under the auspices of the American Society of Reproductive Immunology
      concluded that contradictory results of investigations could be caused by the
      heterogeneity of study groups. Because of controversy about the efficacy of
      allogeneic leukocytes immunization for treatment of RSA, intravenous
      immunoglobulin as an alternative treatment have been sought. Small number of
      randomized, controlled trials of IVIG for treatment of RSA have been published.
      Although these results show that IVIG is effective in the treatment of RSA (live
      birth rate of 61-85%), it still is not clear what the ideal dosage is, and how
      frequently and how long IVIG therapy should be given.

PMID- 11848032
TI  - [Strategy in gestational diabetes].
AB  - This paper reviews current literature on strategic policy in gestational diabetes
      (GDM). Emphasis is placed on early identification of carbohydrate intolerance.
      Definitive guidelines related to screening procedures, diagnostic criteria,
      glucose monitoring with threshold for insulin therapy in GDM were briefly
      described. Pregnancy termination and delivery management have been discussed. The
      importance of postpartum follow-up is pointed out. Special attention is paid to
      the association with increased antenatal risk of subsequent diabetes and
      consequently raised perinatal morbidity and/or mortality. For appropriate health
      care a cooperation between patients, obstetricians and diabetologists is
      suggested.

PMID- 11848033
TI  - [The influence of iodine deficiency during pregnancy of fetal and neonatal
      development].
AB  - The iodine is fundamental substrate for thyroid hormones synthesis. Thyroxine and
      triiodothyronine play a crucial role in human brain development and maturation.
      It is well known, that not only fetal, but also maternal thyroid hormones are
      essential for normal prenatal central nervous system development. During
      pregnancy complex changes of maternal thyroid function occur and they are
      influenced by the maternal iodine supply. With decreasing iodine intake, maternal
      goiter and hypothyroxinemia as well as fetal and neonatal hypothyroidism become
      more prevalent. The severity of iodine deficiency and hypothyroidism in the
      mother during early and midgestation is related to the severity of the neural
      damage in the fetus. In severe iodine deficiency, central nervous system damage
      is already irreversible at birth and can only be prevented by correction of the
      maternal iodine deficiency early in pregnancy. Therefore iodine supplementation
      during pregnancy is now strongly recommended.

PMID- 11848034
TI  - [Impacted maxillary cuspid. II. Releasing by means of a modified fenestration
      technique].
AB  - A review of the treatment of the impacted upper cuspid is presented. A
      description of a modified exposure technique is given. Up to the present day more
      than 400 impacted cuspids have been treated with this technique.

PMID- 11848036
TI  - [Extraction of second molars as orthodontic therapy].
AB  - Extraction of second molars as an orthodontic measure is a simple procedure which
      can lead to good clinical results. Indications as well as timing and long term
      effects on buccal occlusion are discussed. It is concluded that acceptable
      results may only be expected when the extraction is strictly indicated and
      carried out in cases when the third molars have reached their full crown stage
      but before radiographic evidence of root formation. Upper third molars with an
      angulation of less than 30 degrees and lower third molars with an angulation of
      30-60 degrees to the occlusal plane are likely to give a satisfactory position
      after eruption.

PMID- 11848035
TI  - [Impacted maxillary cuspid. IV. Periodontal aspects].
AB  - Treatment goal of the maxillary impacted cuspid should include health periodontal
      end results. This clinical and radiographic study reveals in 75% of the cases a
      satisfying periodontal condition.

PMID- 11848037
TI  - [Dentin remineralization induced by glass ionomers].
AB  - Using an intra-oral model the effects of restorations on adjacently placed
      demineralized dentine were studied. After 12 weeks in situ, glass ionomer induced
      hypermineralization of dentine, in particular at the surface in contact with the
      filling. Next to amalgam restorations the dentine was found to be further
      demineralized.

PMID- 11848038
TI  - Bibliography. Current World Literature. Arrhythmias.

PMID- 11848039
TI  - 1997 membership directory.

PMID- 11848040
TI  - Pectoral and thoracic symptoms and shunt malfunction.

PMID- 11848041
TI  - Episodes of symptomatic shunt insufficiency related to outcome at the mean age of
      30: a community-based study.

PMID- 11848042
TI  - Extracellular space volume changes and diffusion barriers in rats with kaolin
      induced and inherited hydrocephalus.

PMID- 11848043
TI  - Water-imbalance-induced expression of FGF-2 in fluid-regulatory centers: choroid
      plexus and neurohypophysis.

PMID- 11848044
TI  - Intermittent lumbar drainage with functional testing in the diagnosis of normal
      pressure hydrocephalus.

PMID- 11848045
TI  - Acute retention of urine in babies with meningomyelocele.

PMID- 11848046
TI  - The neuropathic bowel in spina bifida--a cross-sectional study in 226 patients.

PMID- 11848047
TI  - Inherited hydrocephalus in the H-Tx rat: the ventricular system in late-gestation
      and neonatal aqueduct stenosis.

PMID- 11848048
TI  - Behavioral and emotional problems in children with myelomeningocele (MMC).

PMID- 11848049
TI  - Hydrocephalus internus--first manifestation of chronic meningitis due to Listeria
      monocytogenes.

PMID- 11848050
TI  - Clinical risk: identifying latex allergy in adults with spina bifida.

PMID- 11848051
TI  - Performance of a novel antisiphon device in the presence of raised CSF protein
      and blood.

PMID- 11848052
TI  - Why is the occurrence of open spina bifida so relevant? The recent experience of
      a Portuguese spina bifida center.

PMID- 11848053
TI  - Lactation after gestation affects the expression of inherited hydrocephalus in H
      Tx rats.

PMID- 11848054
TI  - Endoscopic third ventriculostomy for obstructive hydrocephalus in the pediatric
      population: evaluation of outcome.

PMID- 11848055
TI  - Detrusor sling bladder neck closure in bladder reconstruction.

PMID- 11848056
TI  - Ventriculoperitoneal shunt infection and appendicitis in children.

PMID- 11848057
TI  - Susceptibility of Staphylococcus epidermidis biofilm in CSF shunts to
      bacteriophage attack.

PMID- 11848058
TI  - Failure in cell proliferation in the germinal epithelium of the HTx rats.

PMID- 11848059
TI  - ['Caring: always'; physicians' expression of condolences to the relatives of
      patients].

PMID- 11848061
TI  - Gas analyser connector.

PMID- 11848060
TI  - Syringe identification in the emergency situation.

PMID- 11848062
TI  - Preoperative mouthwash--comfort for the patient; and the anaesthetist.

PMID- 11848063
TI  - Pulse oximetry interference in paediatric neurosurgery.

PMID- 11848064
TI  - Metalloproteinase-9 in critically patients.

PMID- 11848065
TI  - Plastic in anaesthetic circuit.

PMID- 11848067
TI  - Flow reversal through the anaesthetic machine back bar: an unusual assembly
      fault.

PMID- 11848066
TI  - ABC: back to basics with anaesthetic breathing components.

PMID- 11848068
TI  - Incorrectly colour coded flow meters.

PMID- 11848069
TI  - Zyban: anaesthetic considerations.

PMID- 11848070
TI  - The cost of multicompartment 'big bag' total parenteral nutrition in an ICU.

PMID- 11848071
TI  - False positive epidural catheter aspiration tests in CSE.

PMID- 11848072
TI  - Warning stickers and epidural haematomas.

PMID- 11848073
TI  - The role of paraldehyde and lidocaine in the management of status epilepticus.

PMID- 11848074
TI  - [Speechless visitor in the Sauna].

PMID- 11848075
TI  - [Some aspects of the history of tuberculosis with special reference to Finland].
AB  - A popular theory has been that Mycobacterium (M) tuberculosis evolved from M.
      bovis after cattle domestication. The evidence of M. tuberculosis complex in the
      Western Hemisphere before Columbus and the paleopathological evidence from the
      Near East indicate that this relationship between cattle domestication and
      evolution of tuberculosis might not have been so straightforward. Tuberculosis
      was already familiar in Scandinavia during the Middle Ages. In Finland
      consumption was firmly established in both towns and countryside at the end of
      the 1700s and the epidemic peaked during the following century. Tuberculosis
      infection must have been an almost universal feature of childhood in many areas
      of Finland, even in the early decades of the 20th century. After the Second World
      War, specific and effective chemotherapy and preventive measures rapidly
      diminished the number of new cases of tuberculosis.

PMID- 11848076
TI  - [A history of the electrocardiogram].
AB  - The discoveries by Galvani and Volta of electricity and its effects fascinated
      the intellectual world, but it was not until 1856 that Kollicker and Muller
      discovered that the heart muscle could produce electric activity. Muirhead in
      London recorded the first electrocardiogram (ECG) in man in 1869 or 1870 with a
      siphon instrument and Waller in 1887 with a capillary electrometer. Einthoven's
      string galvanometer was a breakthrough. As early as five years after his
      publication Einthoven introduced "Le Telecardiograme" in 1906 by which a cable
      connected his instrument to a hospital one and a half kilometres away. The string
      galvanometer produced precise ECG recordings but it was like the opera
      primadonnas of the time, voluminous and unpredictable. Rune Elmqvist developed
      the direct-writing inkjet recorder, first demonstrated at the Congress of
      Cardiology in Paris, 1950. Ohnell's studies of preexcitation, to which the WPW
      syndrome belongs, were important. After the initial focus on arrhythmias, ECG
      became more and more used in the diagnosis of myocardial ischaemia and coronary
      heart disease. To refine this diagnosis the hypoxaemia (breathing air with low
      oxygen content) test, as well as the exercise test and other stress tests were
      introduced. Vectorcardiography displays the spatial movements of the electrical
      forces generated by the heart. Long-term ECG registration with a portable tape
      recorder is important both for the diagnosis of arrhythmias and myocardial
      ischaemia. Foetal and comparative ECG have provided important clinical and
      scientific information.

PMID- 11848077
TI  - [The technicalization of medicine in the 19th century].
AB  - The paper focuses on the role that instruments played in the medical discourse of
      the 19th century. Towards the end of the century, instruments had imbued the
      medical sciences to such an extent that the situation soon was compared to the
      vernacular confusion of the biblical tower of Babel. Whereas the autonomical
      recordings of laboratory apparatus, vouched for guarantee against biased test
      results, clinicians and general practitioners were finding it difficult to
      incorporate the new techniques into their daily routines. A tension between the
      instrument as invention, moulded to fit a particular series of experiments, and
      the instrument as a reproducible item, was inevitable. Hence, the unification of
      the science and practice of medicine, became an important topic at the
      international medical meetings of the late 19th century. Seen in the light of the
      industrialization and urbanization of occidental culture and society, the
      instrumentation of medicine entailed a number of significant issues which hinged
      on the relationship between the biological destiny of man and the artificial
      wonders of technology. Grand metaphors like the organic machine and the human
      motor, did not only signal a scientific preoccupation with the shortcomings of
      the living organism as opposed to the perfection of the machine, but also
      indicated closer ties between the human body and technology at large. In a
      certain sense, medical instruments, along with apparatuses such as the camera,
      the steam-engine, the telegraph, the phonograph and the cinematograph, offered a
      new set-up of codes with which the body and its functions could be reinterpreted.
      In this respect, the late nineteenth-century strive for the standardisation and
      unification of medical instruments, was not irreconcilable with the notion of the
      l'homme moyen, as conceived, for example, in the work of the Belgian
      mathematician Adolphe Quetelet. The paper outlines the span of medical measuring
      devices, dating from the sphygmometer of Jules Herisson to the technical
      obsession of the late 19th century physiologists. During the course of fifty
      years, the purpose of Herissons instrument, to achieve a common nomenclator for
      the evaluation of human blood pressure, had been driven to its extreme.
      Fascinated with the wonders and possibilities of sheer technology, physiologists
      cultivated the cult of the instrument to such a degree that the very evidence of
      organic phenomena, was transfigured into graphical projections, the monotonous of
      the telephone and other technical manifestations.

PMID- 11848078
TI  - Israel suggests limits on right to die.

PMID- 11848079
TI  - Recognizing and valuing higher level practice.

PMID- 11848080
TI  - Culture of care in nursing homes in need of further research.

PMID- 11848081
TI  - Mortality rates unveiled in wake of Bristol deaths.

PMID- 11848082
TI  - Patients' forums to replace CHCs.

PMID- 11848083
TI  - NICE is "flawed", say consumer groups.

PMID- 11848084
TI  - Milburn says NHS to be decentralized.

PMID- 11848085
TI  - Age discrimination will be solved by legislation.

PMID- 11848086
TI  - Social workers to get code of conduct within the next year.

PMID- 11848088
TI  - Appalling use of staff by NHS trusts.

PMID- 11848089
TI  - Privatization of NHS must not be allowed.

PMID- 11848090
TI  - Homozygous Factor V Leiden mutation in sickle cell anaemia.

PMID- 11848091
TI  - The use of oral vitamin K for reversal of over-warfarinization.

PMID- 11848092
TI  - Allogenic marrow grafts from unrelated donors with congenital pericentric
      inversion of chromosome 9.

PMID- 11848093
TI  - Minimally invasive single-vessel coronary artery bypass with the internal
      thoracic artery and early postoperative angiography: midterm results of a
      prospective study in 120 consecutive patients.
AB  - BACKGROUND: This prospective study was undertaken to determine the role of the
      minimally invasive direct coronary artery bypass with early postoperative
      angiography and midterm follow-up in 120 consecutive patients with single-vessel
      coronary artery disease. METHODS: Minimal access (6 to 10 cm), without complete
      sternotomy and no cardiopulmonary bypass, was used. The lesions were located at
      the proximal left anterior descending coronary artery in 95% of the patients.
      Routine coronary angiography was performed before discharge. RESULTS:
      Postoperative angiography was performed in 104 (90.4%) of those 115 patients who
      had coronary revascularization concluded by the mini-access method. The internal
      thoracic artery patency rate was 98.1% (95.2% grade A). Two (1.7%) patients
      presented with perioperative myocardial infarction, which led to the single in
      hospital death (0.8%). Of the remaining 119 patients, 113 (95.0%) were
      asymptomatic. The event-free probability was 94.9% and the actuarial survival was
      98.3% with 42 months of follow-up. CONCLUSIONS: For selected patients with single
      vessel coronary artery disease and no major myocardial dysfunction, minimally
      invasive direct coronary artery bypass is a safe operation and a less invasive
      alternative to conventional coronary artery bypass grafting.

PMID- 11848094
TI  - Impact of preoperative aortic cusp prolapse on long-term outcome after surgical
      closure of subarterial ventricular septal defect.
AB  - BACKGROUND: Previous reports on the long-term outcome of surgical closure of
      subarterial ventricular septal defect were based on a relatively small number of
      patients. METHODS: We reviewed the long-term outcome of 135 patients who
      underwent closure of their defect and, in light of the findings, assessed the
      impact of preoperative aortic cusp prolapse and surgical interventions on
      occurrence of aortic regurgitation (AR) in the long-term. The patients were
      categorized into three groups for comparison: group I consisted of 79 patients
      with no aortic cusp prolapse and underwent simple closure of ventricular septal
      defect, group II comprised 39 patients with mild to moderate cusp prolapse who
      similarly had only closure of the defect performed, whereas group III comprised
      17 patients who had additional aortic valvoplasty for greater than moderate to
      severe cusp prolapse. RESULTS: Group I patients had significantly higher
      pulmonary arterial pressure (p < 0.001) and ratio of pulmonary blood flow to
      systemic blood flow (p < 0.001). None of these patients had AR before their
      operation, and none experienced AR afterward at a median follow-up of 6.1 years.
      Of the 39 group II patients, 30 (77%) had trivial or mild AR preoperatively. The
      AR improved in 15 patients, remained trivial or mild in 14 and absent in 7, but
      progressed to trivial or mild in 3 at a median follow-up of 3.1 years. None
      required further interventions. In contrast, 14 (82%) of the 17 group III
      patients had moderate to severe AR before operation. The regurgitation improved
      in 10, but remained moderate or severe in 4 and worsened further in 3 at a median
      follow-up of 4.6 years. The freedom from failure of aortic valvoplasty was (mean
      +/- standard error of the mean) 71%+/-11%, 64%+/-12%, and 43%+/-19% at 1, 5, and
      10 years, respectively. An older age at latest follow-up was the only
      identifiable significant risk factor (p = 0.03). CONCLUSIONS: Our data do not
      support the need of aortic valvoplasty for mild to moderate aortic cusp prolapse.
      Close follow-up is warranted in those with greater than moderate to severe cusp
      prolapse despite valvoplasty as there is continued failure on follow-up. Nothing,
      however, is better than early closure of defects before development of aortic
      valve complications.

PMID- 11848095
TI  - Video-assisted thoracic surgery lobectomy for pulmonary sequestration.
AB  - Pulmonary sequestration is a rare developmental abnormality, and the patients
      usually present with recurrent pneumonia. We report a case of video-assisted
      thoracic surgery lobectomy in a 32-year-old woman with an intrapulmonary
      sequestration in the left lower lobe.

PMID- 11848097
TI  - On the originality of the technique described by Sueda and coworkers.

PMID- 11848096
TI  - Recurrence of left ventricular outflow tract obstruction after left anterior
      descending coronary artery revascularization in a patient with hypertrophic
      obstructive cardiomyopathy.
AB  - A patient with known hypertrophic obstructive cardiomyopathy presented with an
      anteroseptal myocardial infarction which resulted in the disappearance of his
      subaortic pressure gradient. Surgical revascularization of his left anterior
      descending coronary artery after the viability of his myocardium had been
      documented led to the recurrence of his left ventricular outflow tract
      obstruction and subaortic pressure gradient.

PMID- 11848098
TI  - Adaptation of commercial immunoassays to analysis of complex biological
      substances.
AB  - An Intracellular Adhesion Molecule I (ICAM-1) immunoassay from R and D Systems,
      and a Melanoma Inhibitory Activity (MIA) immunoassay from Roche Diagnostics were
      tested for accurate quantitation within complex biological substances such as
      cell lysates. Prior to assay, lysates of melanoma cells were treated with
      detergents to obtain soluble antigens. Maximum ICAM-1 and maximum MIA were
      detected after treatment using 0.8% Triton X-100. Two key aspects of assay
      accuracy were: 1) determining the dilutions of test sample that provided accurate
      quantitation (sample range), and 2) performing spiking experiments at these
      dilutions to determine absence or presence of a "matrix" effect due to biological
      complexity of the sample. A high degree of accuracy was found by diluting this
      particular cellular extract 50-fold prior to ICAM-1 assay, or only 5-fold prior
      to MIA assay. In addition, the bicinchoninic acid protein assay was analyzed to
      test the accuracy of protein quantitation of cellular lysates. Precision, limits
      of detection, and quantitation, robustness, linearity, and specificity also were
      tested for the immunoassays.

PMID- 11848099
TI  - A sensitive micro-platelet ELISA technique for screening anti-HLA antibodies.
AB  - An enzyme-linked immunosorbant assay (ELISA) in a Terasaki plate (Micro-Platelet
      ELISA), using 30000 platelets per well, 2 microL primary antibody (anti HLA
      antiserum) and 5 microL of secondary antibody (1:2000) are described. Platelets
      from 30 selected HLA tissue typed cell panel individuals were used to
      characterize anti HLA A and B antibodies. The first half of the Terasaki tray had
      platelets in sequence to characterize anti HLA antibodies, while the second half
      contained anti HLA B antibodies. Results revealed that the HLA specificities of
      the sera identified by micro-platelet ELISA and microlymphocytotoxicity were
      concordant. Moreover, split antigens of broader specificities were identified in
      the Platelet ELISA technique. The advantages of micro-platelet ELISA technique
      were: (i) it does not require viable/frozen lymphocytes, (ii) reading is very
      simple and macroscopic, (iii) specificity of the serum is identified with
      accuracy within the same day, (iv) avoids inter-cell, inter-day variations, (v)
      complement is not required, (vi) requires only 1/50 volume of the reagents
      required by conventional ELISA in microtitre plates, and (vii) using platelets
      isolated from 5 mL of peripheral blood, fifteen thousand sera can be tested. This
      technique is, thus, very simple, cost effective, and very much suitable for any
      developing HLA laboratory, which is in the process of developing indigenous HLA
      reagents.

PMID- 11848100
TI  - Immunoassay for measuring the heparin-binding growth factors HARP and MK in
      biological fluids.
AB  - Heparin-affin regulatory peptide (HARP) and Midkine (MK) belong to a family of
      growth/differentiation factors that have a high affinity for heparin. The
      involvement of these molecules in various proliferative diseases prompted us to
      develop an assay for measuring the concentrations of these factors in biological
      fluids and culture media. This report describes an immunoassay that uses only
      commercially available materials, based on the high affinity of certain molecules
      for heparin. It consists of adsorbing heparin-BSA covalent complexes to
      microtiter plate wells and to quantify the heparin bound HARP or MK by using
      appropriate antibody. The method is specific and measures concentrations ranging
      from 40-1200 pg/mL HARP and from 25-1200 pg/mL MK and various parameters are
      investigated. The within-assay coefficient of variation was less than 5% for both
      assays. The method was checked by measuring the concentrations of these growth
      factors in the sera of healthy humans and in patients with cancer. As previously
      reported, we confirmed that the serum concentrations of MK are higher in patients
      with tumours (n = 139) than in controls (n = 19). The synthesis of HARP and MK by
      various cells in culture was also analysed.

PMID- 11848101
TI  - Two-step sandwich enzyme immunoassay using monoclonal antibodies for detection of
      soluble and membrane-associated human membrane type 1-matrix metalloproteinase.
AB  - A two-step sandwich enzyme immunoassay (EIA) system for the detection of human
      membrane Type 1-matrix metalloproteinase (MT1-MMP) was established by using two
      monoclonal antibodies against recombinant MT1-MMP. MT1-MMP in which samples were
      reacted with solid-phase antibody and then detected with peroxidase-labeled
      second antibody. At least 1.25 ng/mL was detected by the EIA system, and
      linearity was obtained between 1.25 and 160 ng/mL. This EIA system is specific
      for MT1-MMP and did not show cross-reactivity against several other MMP's
      examined. Shedding of soluble MT1-MMP into the medium by some cancer cell lines
      was also detected by this system. However, soluble MT1-MMP in serum from normal
      and cancer patients was under the detection limit. Membrane-associated MT1-MMP of
      cancer cell lines was also detected after solubilization of the membranes with
      extraction buffer containing detergent. Additionally, MT1-MMP in clinical samples
      was examined. Elevated levels of MT1-MMP were detected in homogenate of cancer
      tissue compared with the levels for normal tissue and the level of MT1-MMP in
      tumors correlated with the rate of metastasis to the regional lymph nodes. Thus,
      we demonstrated that this EIA system is the first to measure MTI-MMP in clinical
      specimens, thus suggesting its useful for diagnosis of cancer or prediction of
      malignancy.

PMID- 11848102
TI  - Effects of the competitor on antibody-hapten binding in immunoassays.
AB  - The effects of competitors on antibody (Ab)-hapten binding in an immunoassay were
      investigated using a goat antimethamphetamine (MA) antibody (Ab). An N-4
      aminobutyl derivative of methamphetamine (4-ABMA) was conjugated with keyhole
      limpet hemocyanine (KLH) and used as an immunogen. The antiserum was purified by
      affinity chromatography with various ligands, including 4-ABMA-protein
      conjugates, free haptens, and protein G. Direct and indirect competitive enzyme
      linked immunosorbent assays (ELISA) were conducted with a competitor of 4-ABMA
      fluorescein isothiocyanate (4-ABMA-FITC). The results were compared to those of
      ELISA with a different competing antigen, 4-ABMA-ovalbumin (4-ABMA-OVA), in terms
      of sensitivity and specificity. In both direct and indirect assay formats, the
      sensitivity was much improved with 4-ABMA-FITC, compared to that with 4-ABMA-OVA,
      suggesting that different labels on the same haptenic moiety for competitors
      considerably influence the assay performance. All the purified Abs also showed a
      distinct feature of strong affinity for benzphetamine with 4-ABMA-FITC, whereas
      they had their respective binding specificities with 4-ABMA-OVA. Comparing the
      results to those from other assay systems, we determined that the assay
      sensitivity was dependent on both the system and the competitor employed, and
      that the specificity was primarily dependent on the competitor used.

PMID- 11848103
TI  - Quantitation of hyaluronic acid in serum with automated microparticle photometric
      agglutination assay.
AB  - A microparticle photometric agglutination assay to quantitate hyaluronic acid
      (HA) in serum has been developed. The principle of the method is that hyaluronic
      acid binding protein covalently sensitized on microparticle surface initiates the
      particles to agglutinate in the presence of HA. By measuring the time-course of
      transmittance changes at 800 nm, due to the particles' agglutination, HA
      concentration is estimated as a function of the magnitude of agglutination in a
      fully automated immunochemistry analyzer. The analytical range for HA was found
      to be between 10 and 1200 ng/mL. The precision (CV) was between 3.0 and 8.4% in
      the intra-assay (n = 10), and 4.8 and 8.9% in the inter-assay (n = 3). The lower
      limit of detection was 10 ng/mL. The deviation of the linearity study indicated
      within 8% of expected values, and the analytical recovery was between 96.5 and
      106.3%. The correlation coefficient against HA plate ELISA was 0.989 with a slope
      of 1.01 (n = 31).

PMID- 11848104
TI  - Free thyroxine solid-analog immunoassays. investigation of the albumin effect on
      the antibody binding to immobilized thyroxine-protein conjugates.
AB  - A reliable one-step, analog-based FT4 immunoassay should be characterized by
      minimal binding of the serum thyroxine-binding proteins to thyroxine-analogs,
      used either as liquid-phase tracers or as solid-phase reagents. In this work, we
      investigated the effect of serum albumin concentration on the anti-T4 antibody
      binding to immobilized T4-protein conjugates with respect to the molecular weight
      (MW) and the T4-to-protein molar ratio of the conjugates. It was found that the
      presence of albumin in the serum sample, at concentrations up to 120 g/L,
      slightly decreased the antibody binding to the immobilized conjugates (less than
      10%). In addition, this decrease was independent of both the MW and the T4-to
      protein molar ratio of the conjugates. On the other hand, using the same
      conjugates as liquid-phase labeled analogs, the observed decrease ranged between
      2 and 33%, depending on the MW of the conjugate. These findings indicate that the
      use of immobilized T4-protein conjugates may improve FT4 immunoassay reliability,
      concerning, especially, the issues of serum albumin concentration and/or affinity
      alterations.

PMID- 11848105
TI  - Skeletal adaptation to external loads optimizes mechanical properties: fact or
      fiction.
AB  - The skeleton adapts to a changing mechanical environment but the widely held
      concept that bone cells are programmed to respond to local mechanical loads to
      produce an optimal mechanical structure is not consistent with the high frequency
      of bone fractures. Instead, the author suggests that other important functions of
      bone compete with mechanical adaptation to determine structure. As a consequence
      of competing demands, bone architecture never achieves an optimal mechanical
      structure.

PMID- 11848106
TI  - Prognostic value of positron emission tomography in cryptogenic West syndrome.
AB  - The relationship between positron emission tomography (PET) findings and
      developmental or seizure outcome was examined in 17 infants (11 males, six
      females; mean age at onset of spasms 7 months, range 3 to 26 months) with newly
      diagnosed cryptogenic West syndrome. The predictive value of PET in these infants
      was assessed. PET was performed in the infants at the onset of spasms and 3
      months after initial therapy using 18F-labelled 2-deoxy-2-fluoro-D-glucose. A
      third PET was performed at 18 months of age if the second scan was abnormal. All
      infants were followed up until at least 3 years of age. Cortical hypometabolism
      was detected in 11 infants on the first PET and in five infants on the second.
      Rate of developmental delay at the last follow-up was significantly higher in
      infants with hypometabolism on the second PET than in those without PET
      abnormalities (p<0.05). Rate of seizure occurrence after initial treatment was
      higher in infants with cortical hypometabolism on the second PET, but the
      difference was not statistically significant. Results suggest that when PET after
      the initial treatment shows no abnormalities, even though the first PET shows
      hypometabolism, infants with cryptogenic West syndrome may have a favourable
      developmental or seizure outcome. PET may be a useful tool in evaluating the
      prognosis in infants with cryptogenic West syndrome.

PMID- 11848107
TI  - What does the Ashworth scale really measure and are instrumented measures more
      valid and precise?
AB  - This study aimed to explore the limitations of the Ashworth scale for measuring
      spasticity. An isokinetic dynamometer to quantify resistance to passive stretch
      and surface EMG was used to verify if a stretch response occurred and, if so, at
      what joint angle. The authors sought to determine which components of passive
      resistance (magnitude, rate of change, onset angle of stretch, or velocity
      dependence) were most related to Ashworth scores and which were related to motor
      function in cerebral palsy (CP). Twenty-two individuals with spastic CP (11
      males, 11 females; mean age 11.9 years, SD 4.3) and a comparison group of nine
      children without CP (four males, five females; mean age 11.3 years, SD 2.5)
      participated in the study. The group with CP included those with a diagnosis of
      spastic diplegia, hemiplegia, or quadriplegia, distributed across Gross Motor
      Functional Classification Levels. Procedures included: (1) clinical assessment at
      the knee joint, (2) functional assessments, and (3) isokinetic assessment of
      passive resistance torque in hamstrings and quadriceps at three velocities. EMG
      data were recorded simultaneously to identify stretch responses. Detecting
      stretch responses using the Ashworth scale compared with instrumented measures
      showed near complete agreement at extremes of the scale, with marked
      inconsistencies in mid-range values. Ashworth scores were correlated with
      instrumented measures, particularly for the quadriceps, with higher correlations
      to the rate of change in resistance (stiffness) and onset angle of stretch than
      to peak resistance torque. Those with greater resistance tended to have poorer
      function with isokinetic relations typically stronger.

PMID- 11848108
TI  - Pathological long-bone fractures in residents with cerebral palsy in a long-term
      care facility in South Africa.
AB  - A high incidence of long-bone fractures has been observed in children and young
      adults with quadriplegic cerebral palsy in residential care. This study aimed to
      determine factors that contribute to these fractures and to institute preventive
      treatment. Twenty individuals (12 males, eight females) of a cohort of 88
      residents with spastic quadriplegia in residential care in Gauteng, South Africa
      who had sustained fractures were compared with a random sample of age-matched
      control participants (10 males, 10 females) from the same facility. Participants
      ranged in age from 6 to 29 years (median 17.5 years). The majority of fractures
      were in the upper extremities. There was radiological and biochemical evidence of
      rickets and osteomalacia in both groups. However, the severity of the disease was
      more pronounced in the group with fractures. There was a significant relation
      (p=0.002) between the number of fractures and the use of anticonvulsant therapy
      (ACT). Three months of vitamin D administration (calciferol 5000 iu/day) resulted
      in a marked clinical improvement. There were no fractures during this period in
      either group. In addition, the mean serum calcium (Ca) and phosphate (Pi) levels
      increased (Ca from 2.17 to 2.35 mmol/L and Pi from 1.13 to 1.66 mmol/L) and mean
      total alkaline phosphatase level decreased (from 1123 to 423 U/L). We concluded
      that vitamin D deficiency was the major factor contributing to the occurrence of
      fractures in this population. Unless sunlight exposure can be guaranteed, vitamin
      D supplementation should be considered for children and adults in residential
      care, especially if they are on ACT, even in areas with year-round sunshine.

PMID- 11848110
TI  - Somatosensory testing in idiopathic scoliosis.
AB  - Sixty-seven consecutive patients (59 females, eight males; mean age 13.6 years,
      age range 8.1 to 18 years) with adolescent idiopathic scoliosis were evaluated
      for segmental dystonia, thermal and vibratory thresholds, and cortical
      somatosensory evoked potentials (cSEPs). Clinically, there were no signs of
      segmental dystonia. No significant side difference was found in cSEPs and thermal
      thresholds. Vibration thresholds were increased on the right side with a
      significant side difference at all sites. However, these changes did not
      correlate to curve size, rotation, curve type, or convexity. It was concluded
      that, at the present level of somatosensory testing, no segmental
      neurophysiological disturbance can be related to the appearance of idiopathic
      scoliosis. The importance of asymmetric vibratory thresholds measurements cannot
      be deduced from this study.

PMID- 11848109
TI  - Hearing loss in early infancy affects maturation of the auditory pathway.
AB  - The influence of early cochlear hearing loss on maturation of the auditory
      pathway was studied by measuring auditory brainstem responses (ABR). In a
      retrospective study, 85 children with normal hearing (46 males, 39 females; age
      range 2 months to 14 years) and 165 children with binaural cochlear hearing
      impairment (89 males, 76 females; age range 1 month to 16 years) were examined. A
      significant positive correlation (p<0.001) between the degree of hearing loss and
      interpeak latencies I-V (IPL(I-V)) of the ABR was observed. No significant
      correlation (p=0.85) was found between hearing loss and interpeak latencies I-III
      (IPL(I-III)). These findings can be interpreted as indicating a marked delay in
      maturation of higher brainstem structures due to reduced auditory input during
      infancy. The correlation differs notably from results of comparable studies of
      adults published in recent literature. This leads to the assumption that the
      developing human brain is particularly sensitive to auditory deprivation. Thus,
      our results indicate the importance of a normal acoustic environment during
      sensitive periods in early childhood to ensure normal hearing and speech
      development.

PMID- 11848111
TI  - Genetic medicine and the muscular dystrophies: triumphs and tribulations.

PMID- 11848112
TI  - Foetal alcohol syndrome--a multifaceted condition.

PMID- 11848113
TI  - Information for the clinician in the 21st century.

PMID- 11848114
TI  - Effects of iodine supplementation during pregnancy on child growth and
      development at school age.
AB  - Growth and development of 207 children (49% males; mean age 5.4 years [SD 0.2],
      range 4 to 7.3 years whose mothers received iodine during pregnancy, and children
      who received iodine first in their 2nd year, were examined in 1996; 192 children
      (49% males; mean age 6.5 years [SD 0.2], range 5.8 to 6.9 years) whose mothers
      received iodine while pregnant were seen in 1998. Children were from the southern
      part of China's Xinjiang Province which has the lowest levels of iodine in water
      and soil ever recorded. Head circumference but not height was improved for those
      who received iodine during pregnancy (compared with those receiving iodine at age
      2) and for those supplemented before the end of the 2nd trimester (relative to
      those supplemented during the 3rd trimester). Iodine before the 3rd trimester
      predicted higher psychomotor test scores for children relative to those provided
      iodine later in pregnancy or at 2 years. Results from the test for cognitive
      development resulted in trend only differences between those children
      supplemented during pregnancy versus later. The results address the question of
      when maternal iodine supplements should begin in public health programs world
      wide. Findings may be relevant to the treatment of maternal and newborn thyroid
      deficiency in industrialized countries, particularly for those infants delivered
      before the end of the second trimester.

PMID- 11848115
TI  - Effect of auditory, tactile, visual, and vestibular intervention on length of
      stay, alertness, and feeding progression in preterm infants.
AB  - This study determined whether an auditory, tactile, visual, and vestibular
      intervention (ATVV) reduced the length of hospitalization of 37 preterm infants
      by increasing the proportion of alert behavioral states, thereby improving their
      feeding progression. Participants comprised 12 infants born between 23 and 26
      weeks' gestation with normal head ultrasounds and 25 CNS-injured infants born
      between 23 and 31 weeks' gestation. Infants were randomly assigned to the control
      group (11 males, five females) or study group (seven males, 14 females) at 32
      weeks' postconceptional age. ATVV intervention was administered to the study
      group for 15 minutes, twice daily, 5 days per week, from 33 weeks of age until
      discharge. The study group demonstrated increased alertness during the first 5
      minutes of intervention, which was significantly correlated to length of stay
      (p<0.05). The proportion of nippled (teat) intake increased significantly faster
      for the study group (p=0.0001). Infants in the study group were discharged at a
      mean of 36.54 weeks, 1.6 weeks earlier than control infants (p<0.05). ATVV
      intervention facilitated increased alertness, faster transition to complete
      nipple feeding, and decreased length of hospitalization.

PMID- 11848116
TI  - MRI findings in children with school problems who had been exposed prenatally to
      alcohol.
AB  - This study examined 17 children (nine males, eight females; mean age 13 years)
      with prenatal alcohol exposure of various durations. The aim of the study was to
      detect specific brain morphological alterations by means of MRI and to see if
      findings correlated with particular cognitive deficits. Of the 17 children, five
      had been exposed to heavy maternal consumption of alcohol (over 10 drinks/week)
      during the first trimester only; four had been exposed during the first and
      second trimester; and eight had been exposed throughout pregnancy. Five children
      had alcohol related neurobehavioural disorder, seven were diagnosed as having
      foetal alcohol effects and five were diagnosed as having foetal alcohol syndrome.
      Hypoplasia of the vermis was observed in 10 children and malformed posterior
      vermis in one additional child. Five children had hypoplastic cerebellar
      hemispheres. Hypoplasia of the corpus callosum was observed in two children.
      Small hippocampi were observed in three children and wide cortical sulci in six.
      No specific structural anomaly correlated with a particular neuropsychological
      deficit. In this study, deviations in the development of the vermis was the most
      sensitive morphological indicator of the effects of prenatal alcohol exposure. It
      was seen in every diagnostic group including children who had been exposed during
      only the first trimester of pregnancy.

PMID- 11848117
TI  - Accelerated Monte Carlo based dose calculations for brachytherapy planning using
      correlated sampling.
AB  - Current brachytherapy dose calculations ignore applicator attenuation and tissue
      heterogeneities, assuming isolated sources embedded in unbounded medium.
      Conventional Monte Carlo (MC) dose calculations, while accurate, are too slow for
      practical treatment planning. This study evaluates the efficacy of correlated
      sampling in reducing the variance of MC photon transport simulation in typical
      brachytherapy geometries. Photon histories were constructed in the homogeneous
      geometry and weight correction factors applied to account for the perturbing
      effect of heterogeneities. Two different estimators, expected value track-length
      (ETL) and analogue (ANL), were used. The method was tested for disc-shaped
      heterogeneities and point-isotropic sources as well as for a model 6702 125I
      seed. Uncorrelated ETL estimation was 10-100 times more efficient than its ANL
      counterpart. Correlated ETL estimation offered efficiency gains as large as 10(4)
      in regions where dose perturbations are small (<5%). For perturbations of 40-50%,
      efficiency gains were in some cases even less than unity. However, correlated ETL
      was capable of producing less than 2% (I standard deviation) uncertainty in more
      than 90% of the voxels in 1 CPU hour. Correlated sampling significantly improves
      efficiency under selected circumstances and, in combination with other variance
      reduction strategies, may make MC-based treatment planning a reality for
      brachytherapy.

PMID- 11848118
TI  - Full forward Monte Carlo calculation of portal dose from MLC collimated treatment
      beams.
AB  - This work deals with a full Monte Carlo (MC) simulation of a radiotherapy
      treatment facility including a multi-leaf collimator (MLC) and electronic portal
      imaging device (EPID). A method for a planar calibration of the EPID response in
      terms of dose using the MC technique is presented. Calibration measurements and
      simulations with several blocks of attenuating material are carried out down to
      approximatively 5% of the open field transmitted dose. A linear relationship is
      shown between the squared EPID signal and the MC calculated dose. The calibrated
      EPID was used as a dosimetric system to validate a MC model for the MLC.
      Computations and measurements agreed within 2% of dose difference (or 2 mm in
      regions of high dose gradient). The technique described herein is not
      significantly limited by physics transport model constraints. Therefore it can
      potentially provide a more accurate verification of dose delivery to
      inhomogeneous anatomical regions in patients undergoing complex multi-field
      conformal or intensity-modulated radiation therapy.

PMID- 11848119
TI  - The effect of dose calculation accuracy on inverse treatment planning.
AB  - The effect of dose calculation accuracy during inverse treatment planning for
      intensity modulated radiotherapy (IMRT) was studied in this work. Three dose
      calculation methods were compared: Monte Carlo, superposition and pencil beam.
      These algorithms were used to calculate beamlets. which were subsequently used by
      a simulated annealing algorithm to determine beamlet weights which comprised the
      optimal solution to the objective function. Three different cases (lung, prostate
      and head and neck) were investigated and several different objective functions
      were tested for their effect on inverse treatment planning. It is shown that the
      use of inaccurate dose calculation introduces two errors in a treatment plan, a
      systematic error and a convergence error. The systematic error is present because
      of the inaccuracy of the dose calculation algorithm. The convergence error
      appears because the optimal intensity distribution for inaccurate beamlets
      differs from the optimal solution for the accurate beamlets. While the systematic
      error for superposition was found to be approximately 1% of Dmax in the tumour
      and slightly larger outside, the error for the pencil beam method is typically
      approximately 5% of Dmax and is rather insensitive to the given objectives. On
      the other hand, the convergence error was found to be very sensitive to the
      objective function, is only slightly correlated to the systematic error and
      should be determined for each case individually. Our results suggest that because
      of the large systematic and convergence errors, inverse treatment planning
      systems based on pencil beam algorithms alone should be upgraded either to
      superposition or Monte Carlo based dose calculations.

PMID- 11848120
TI  - Dosimetry system for the irradiation of thin biological samples with therapeutic
      proton beams.
AB  - The design and performance of a dosimetric system for the irradiation of thin
      biological samples with therapeutic proton beams is reported. Protons with
      initial energies between 40 MeV and 250 MeV are degraded with polystyrene blocks
      of variable thickness in order to place the sample, an aqueous layer of 10 microm
      thickness, at various locations on the proton depth-dose curve. The dosimetric
      system comprises a secondary emission monitor, a Faraday cup and thin ionization
      chambers, which are located upstream of the sample, and a calcium fluoride
      scintillator located downstream of the sample for monitoring the position of the
      sample relative to the Bragg peak. Transverse dose profiles were measured with
      radiochromic films. System performance was studied and optimized by simulating
      primary radiation transport through detectors, degrader and sample using the
      Monte Carlo simulation tool GEANT 3.21. Calculated detector responses and beam
      profiles agreed well with the measured data. Monte Carlo simulation was also used
      to evaluate mean values and spectra of linear energy transfer in the sample as a
      function of initial proton energy and degrader thickness. Long-term experience
      has shown that the system performance was unchanged after accumulated doses of
      10(5) Gy.

PMID- 11848121
TI  - Absorbed dose to water based dosimetry versus air kerma based dosimetry for high
      energy photon beams: an experimental study.
AB  - In recent years, a change has been proposed from air kerma based reference
      dosimetry to absorbed dose based reference dosimetry for all radiotherapy beams
      of ionizing radiation. In this paper, a dosimetry study is presented in which
      absorbed dose based dosimetry using recently developed formalisms was compared
      with air kerma based dosimetry using older formalisms. Three ionization chambers
      of each of three different types were calibrated in terms of absorbed dose to
      water and air kerma and sent to five hospitals. There, reference dosimetry with
      all the chambers was performed in a total of eight high-energy clinical photon
      beams. The selected chamber types were the NE2571, the PTW-30004 and the
      Wellhofer-FC65G (previously Wellhofer-IC70). Having a graphite wall, they exhibit
      a stable volume and the presence of an aluminium electrode ensures the robustness
      of these chambers. The data were analysed with the most important recommendations
      for clinical dosimetry: IAEA TRS-398, AAPM TG-51, IAEA TRS-277, NCS report-2
      (presently recommended in Belgium) and AAPM TG-21. The necessary conversion
      factors were taken from those protocols, or calculated using the data in the
      different protocols if data for a chamber type are lacking. Polarity corrections
      were within 0.1% for all chambers in all beams. Recombination corrections were
      consistent with theoretical predictions, did not vary within a chamber type and
      only slightly between different chamber types. The maximum chamber-to-chamber
      variations of the dose obtained with the different formalisms within the same
      chamber type were between 0.2% and 0.6% for the NE2571, between 0.2% and 0.6% for
      the PTW-30004 and 0.1% and 0.3% for the Wellhofer-FC65G for the different beams.
      The absorbed dose results for the NE2571 and Wellhofer-FC65G chambers were in
      good agreement for all beams and all formalisms. The PTW-30004 chambers gave a
      small but systematically higher result compared to the result for the NE2571
      chambers (on the average 0.1% for IAEA TRS-277, 0.3% for NCS report-2 and AAPM TG
      21 and 0.4% for IAEA TRS-398 and AAPM TG-51). Within the air kerma based
      protocols, the results obtained with the TG-21 protocol were 0.4-0.8% higher
      mainly due to the differences in the data used. Both absorbed dose to water based
      formalisms resulted in consistent values within 0.3%. The change from old to new
      formalisms is discussed together with the traceability of calibration factors
      obtained at the primary absorbed dose and air kerma standards in the reference
      beams (60Co). For the particular situation in Belgium (calibrations at the
      Laboratory for Standard Dosimetry of Ghent) the change amounts to 0.1-0.6%. This
      is similar to the magnitude of the change determined in other countries.

PMID- 11848122
TI  - Fast formation of statistically reliable FDG parametric images based on
      clustering and principal components.
AB  - Formation of parametric images requires voxel-by-voxel estimation of rate
      constants, a process sensitive to noise and computationally demanding. A model
      based clustering method for a two-parameter model (CAKS) was extended to the FDG
      three-parameter model. The concept was to average voxels with similar kinetic
      signatures to reduce noise. Voxel kinetics were categorized by the first two
      principal components of the tissue time-activity curves for all voxels. k2 and k3
      were estimated cluster-by-cluster, and K1 was estimated voxel-by-voxel within
      clusters. When CAKS was applied to simulated images with noise levels similar to
      brain FDG scans, estimation bias was well suppressed, and estimation errors were
      substantially smaller--1.3 times for Ki and 1.5 times for k3-than those of
      conventional voxel-based estimation. The statistical reliability of voxel-level
      estimation by CAKS was comparable with ROI analysis including 100 voxels. CAKS
      was applied to clinical cases with Alzheimer's disease (ALZ) and cortico basal
      degeneration (CBD). In ALZ, the affected regions had low Ki (K1k3/(k2 +k3)) and
      k3. In CBD, Ki was low, but k3 was preserved. These results were consistent with
      ROI-based kinetic analysis. Because CAKS decreased the number of invoked
      estimations, the calculation time was reduced substantially. In conclusion, CAKS
      has been extended to allow parametric imaging of a three-compartment model. The
      method is computationally efficient. with low bias and excellent noise
      properties.

PMID- 11848123
TI  - Preliminary study on extremely small angle x-ray scatter imaging with synchrotron
      radiation.
AB  - Among the medical physics community, there is nowadays a great interest in the
      possible implementation of scatter imaging techniques, especially in the field of
      breast imaging. It is well known that malignant lesions and normal tissue differ
      in their scattering signatures, and thus scattered radiation can provide a
      powerful tool to distinguish between the two cases. Up to now, most of the
      proposed techniques rely on the detection of radiation scattered at angles of the
      order of a few degrees, which in most cases results in very high contrast values.
      On the other hand, at those relatively large angles the scattered flux is
      relatively low with respect to the primary, which often implies the necessity of
      increasing the dose delivered to the sample in order to achieve sufficient
      statistics. Furthermore, most of these techniques are based on pencil beam set
      ups, which results in an increase of the overall duration of the examination. We
      propose here an alternative approach based on the detection of radiation
      scattered at extremely small angles, of the order of approximately 100-200
      microrad. This results in a relatively high scattered flux (5-10% of the primary)
      and in the possibility of utilizing a fan beam geometry, which reduces the
      acquisition times with respect to pencil beam set-ups. Images of several samples
      have been acquired, demonstrating that the proposed technique results in an
      increased contrast with respect to absorption imaging. Possible in vivo
      implementations of the technique at no dose expense are finally discussed.

PMID- 11848125
TI  - L-shell x-ray fluorescence measurements of lead in bone: system development.
AB  - This paper reports on the development of an L-shell x-ray fluorescence (XRF) bone
      lead measurement system. A secondary target gave greater lead x-ray peak signal
      to-background ratios than partially plane polarized XRF. Filtration did not
      improve the lead x-ray peak signal-to-background ratio: the gains in spectrum
      quality were outweighed by the losses caused by attenuation. There was a
      substantial matrix effect: the signal from a calcium-rich matrix was far lower
      than that from a calcium-free matrix. The effect of attenuation was, as expected,
      profound for the lead L x-rays: detection limits ranged from 18 to 217 microg
      Pb/g plaster with attenuation equivalent to 0-2.1 mm of skin or 0-3.7 mm of
      adipose tissue for the Pb Lalpha x-ray group (10.5 keV), and from 16 to 184
      microg Pb/g plaster with attenuation equivalent to 0-1.3 mm of skin or 0-2.3 mm
      of adipose tissue for the Pb Lbeta x-ray group (12.6 keV).

PMID- 11848124
TI  - L-shell x-ray fluorescence measurements of lead in bone: theoretical
      considerations.
AB  - This paper reviews several theoretical considerations pertinent to the use of
      lead L-shell x-rays for the in vivo measurement of lead in bone: the method of
      correcting for attenuation, the contributions to the measurement uncertainty,
      interferences, the depth of bone sampled and the signal strength. Both the
      predicted bone lead concentration and the measurement uncertainty therein are
      influenced by the choice of linear attenuation coefficient with which to correct
      for overlying tissue. Measurement uncertainty is also influenced by inter
      individual variability in body composition, methodological uncertainty in the
      ultrasound measurement of overlying tissue thickness and discrepancy between the
      site of LXRF and the site of ultrasound measurement. Interference with the Pb
      Lalpha x-rays by As Kalpha has been overstated and is probably negligible,
      interference from lead in non-bone tissues may not be. The depth of bone from
      which the signal is obtained and a crude estimate of signal strength are
      calculated for different bone compositions for both K and L x-ray fluorescence.

PMID- 11848126
TI  - Comment on 'there is no IMRT?'.

PMID- 11848127
TI  - Production of phantom materials using polymer powder sintering under vacuum.
AB  - A technique is presented for the production of polymer-based phantom materials
      from solid polymer powders and various compounds added to adjust x-ray
      attenuation. After mixing of the finely grained components, the samples are
      solidified by a sintering process under vacuum. The method described allows a
      flexible and inexpensive production of phantom materials. Photon attenuation and
      density can be adjusted by suitable choice of base polymers and additives to
      mimic a large range of soft tissues and water.

PMID- 11848128
TI  - Experimental infection of laboratory mice and rabbits with several isolates of
      Borrelia burgdorferi sensu lato; comparison of antigens from different
      genospecies in serological measurement of immune responses.
AB  - Infectivity of and immune responses to 28 Finnish Borrelia burgdorferi sensu lato
      isolates was studied in 3-4-week-old outbred NMRI and inbred BALB/c/Hy laboratory
      mice; rabbits were also inoculated. Twenty-one isolates were found to detectably
      infect mice. A variation among isolates in degree of infectivity was observed.
      Higher infection rate and higher average ELISA readings were recorded for
      intradermal than intraperitoneal inoculations. The results suggest differences
      between Borrelia genospecies in organotropism. The ear was frequently infected by
      representatives of all genospecies; among high infectivity experiments, this rate
      was highest, 100%, in infections by Borrelia afzelii. Further differences between
      genospecies specific organ distributions: B. burgdorferi sensu stricto and
      Borrelia garinii isolates seemed to infect the bladder relatively more frequently
      than B. afzelii did; B. afzelii isolates infected heart relatively more
      frequently than others did. Genospecies specific differences were demonstrated
      between antigens in reactivity, i.e. in their 'sensitivity' as reagents of ELISA
      and IFA methods to measure isolate specific immune responses. Antigens from two
      B. afzelii isolates differed clearly in sensitivity.

PMID- 11848129
TI  - The effect of immunosuppression on protective immunity of turkey poults against
      infection with turkey coronavirus.
AB  - The objective of the present study was to evaluate the protective effect of
      humoral and cellular immunities on turkeys infected with turkey coronavirus
      (TCV). Two trials were conducted with two separate hatches of turkey poults.
      Turkey's were experimentally immunosuppressed with cyclosporin A (CsA) or
      cyclophosphamide (CY) and infected with TCV. Prior to infection, treatment with
      CsA selectively suppressed T cell activity as revealed by 2-3 fold decreased (p <
      0.1) lymphocyte proliferation responses to a T cell mitogen, concanavalin A (Con
      A). Treatment with CY mainly induced B cell deficiency as indicated by
      significant reductions (p < 0.05) in antibody responses to sheep erythrocytes 7
      days after injection. Body weight gain of turkeys treated with CY was
      significantly lower (p < 0.05) than that of untreated turkeys at 9 days post
      infection (PI). Turkeys treated with CY had 1-2 fold higher immunofluorescent
      antibody assay (IFA) scores for TCV antigens (p < 0.05) in the intestine than
      untreated turkeys at 9 or 14 days PI. These results suggested that humoral
      immunity against TCV infection may be important in turkeys.

PMID- 11848130
TI  - Passive immunization with convalescent serum, or oral immunization with formalin
      killed organisms, does not protect mice against gastrointestinal challenge with
      Listeria monocytogenes.
AB  - Listeria monocytogenes is an important foodborne pathogen in both humans and
      animals. In addition, murine listeriosis is a widely used model for studying the
      molecular pathogenesis of an intracellular pathogen, and the regulation of
      protective cellular immunity. Little attention has been paid to protective
      immunity against L. monocytogenes in the gastrointestinal tract, where a
      secretory immune response might prevent attachment of the bacteria to the
      intestinal epithelium. In this study we found that neither opsonization of L.
      monocytogenes with immune serum, nor repeated oral administration of killed L.
      monocytogenes, protected mice against gastrointestinal challenge with L.
      monocytogenes.

PMID- 11848131
TI  - Serotypes of non-O157 verocytotoxigenic Escherichia coli isolated from meat in
      New Zealand.
AB  - Verocytotoxigenic Escherichia coli (VTEC) were isolated from meat in New Zealand.
      They were tested for the presence of virulence factors associated with VTEC and
      serotyped. Some of the serotypes found were identical to ones reported from other
      parts of the world, but some serotypes were also found which had not been
      reported elsewhere. This study confirms the world-wide distribution of these
      emerging food-borne pathogens.

PMID- 11848132
TI  - Study of interleukin-10 and interleukin-12 productions in response to
      lipopolysaccharides extracted from two different Brucella strains.
AB  - The aim of the present study is to investigate the cytokines induction by smooth
      lipopolysaccharides (S-LPS) extracted from Brucella melitensis (Rev1 vaccine
      strain) and Brucella abortus (a field isolate). These lipopolysaccharides were
      used to induce inflammatory cytokines production in peripheral blood cell culture
      of healthy individuals. Secretion of IL-10 and IL-12 (p70) were measured by means
      of specific Elisa. In addition, intracellular expression of IL-12 was assessed in
      CD14+ cells by flow cytometry. It was shown that Brucella LPS is a potent inducer
      of IL-10. However interferon gamma (IFN-gamma) priming was able to significantly
      decrease the production of IL-10. Flow cytometry studies showed that LPS alone
      was not able to induce intracellular IL-12 expression in CD14+ cells.
      Nevertheless, IFN-gamma priming significantly increased the percentage of CD14+
      IL-12+ cells. In conclusion, it was demonstrated that the Brucella LPS could be a
      potent inducer of IL-10 and induction of IL-12 production needs the most
      favorable conditions.

PMID- 11848133
TI  - Antigenic heterogeneity among the field isolates of Newcastle disease virus (NDV)
      in relation to the vaccine strain: 1. Studies on viruses isolated from wild birds
      in Israel.
AB  - In order to reveal the viruses strongly differing from the VH NDV strain used in
      Israel for poultry vaccination, 54 NDV strains isolated during the last 15 years
      in Israel from feral birds were studied by means of the panels of 39 monoclonal
      antibodies. Six isolates were found to have considerable antigenic differences in
      envelope proteins as compared to the vaccine strain. In four cases, the
      differences were related mostly to the hemagglutinin-neuraminidase glycoprotein,
      in one case to the fusion glycoprotein, and in one case to the matrix protein.

PMID- 11848134
TI  - Fulminant heart failure due to selenium deficiency cardiomyopathy (Keshan
      disease).
AB  - Selenium deficiency is a rare cause of cardiomyopathy that may be encountered by
      the forensic pathologist. Selenium deficiency is associated with a
      cardiomyopathy, myopathy and osteoarthropathy. In Asia and Africa, dietary
      selenium deficiency is associated with a cardiomyopathy known as Keshan disease
      and an osteoarthropathy called Kashin-Beck disease. Chronic selenium deficiency
      may also occur in individuals with malabsorption and long term selenium-deficient
      parenteral nutrition. Selenium deficiency causes myopathy as a result of the
      depletion of selenium-associated enzymes which protect cell membranes from damage
      by free radicals. We present a case of fulminant heart failure in a middle aged
      woman with a complex medical and surgical history including documented
      malabsorption and selenium deficiency. Pathological examination of the heart
      showed features consistent with Keshan disease.

PMID- 11848135
TI  - Legal aspects of mental hospital regime in England and Wales.
AB  - Although there are several works on mental hospitals, the legal aspects of mental
      hospital regime have not been comprehensively studied. This paper aims to fill
      that gap as regards England and Wales. The empirical study was conducted in a
      conventional English mental hospital which was within the National Health
      Service. After the introduction and a brief account of modes of admission to
      mental hospitals, the paper focuses on various aspects of mental hospital regime
      such as hospital rules and policies, daily routine, treatment without consent,
      seclusion, close observation, searches of patients and their property,
      restrictions on mail, etc., and then discusses the question of their legality,
      characterised by the tussle between the rights of patients and the rights of
      society. The paper concludes that although the regimes in mental hospitals may be
      considered reasonable and necessary, certain features of them (e.g., treatment
      without consent and searches of patients and their property) are controversial.

PMID- 11848136
TI  - The railway murders: R v John Duffy and R v David Mulcahy.

PMID- 11848137
TI  - Suicide in Puccini's operas!

PMID- 11848139
TI  - The prosecutor's fallacy--a pitfall in interpreting probabilities in forensic
      evidence.
AB  - Forensic evidence is often given in terms of a mathematical probability. However,
      it is easy to make a particular type of error, 'the prosecutor's fallacy', in the
      interpretation of such probability. This paper highlights the source of this
      error and briefly introduces Bayes Theorem as the correct theoretical basis for
      interpreting such evidence. The first Californian legal case in which this error
      was committed is discussed, followed by all cases in the UK in which this error
      was highlighted and rectified by the Court of Appeal. It is important for all
      parties concerned--expert witnesses, lawyers and judges--to understand these
      principles correctly. Furthermore, the criminal courts face dilemmas when juries
      are involved. This paper concludes by discussing recent guidance from the Court
      of Appeal on how such evidence should be presented to the jury and the
      implications of this guidance.

PMID- 11848138
TI  - Personality and neuropsychological function in violent, sexual and arson
      offenders.
AB  - We aimed to test the hypothesis that incarcerated offender populations will not
      differ in neuropsychological test performance if patients are matched on age,
      intelligence and personality profile, particularly if impulsive aggressive traits
      and confounds such as substance misuse and performance anxiety are controlled
      for. 27 violent offenders, 20 sex offenders and 13 arson offenders detained in
      maximum security hospitals completed dimensional assessments of personality
      function and were assessed on a battery of frontal and temporal
      neuropsychological tests. All patients completed a variety of self-report
      measures of cognitive, affective and behavioural dispositions relevant to
      offender populations. Trait impulsivity was further assessed and composite
      impulsivity scores were derived. Assessments of emotional state were administered
      prior to neuropsychological testing. All patients met the criteria for a DSM-III
      R personality disorder diagnosis. There were no significant group differences in
      age, IQ, or educational attainment. There were no differences in the personality
      profile of the offender group although sex offenders scored higher on trait
      anxiety, depression and tension measures. Groups did not significantly differ in
      their performance on neuropsychological tests apart from poorer perseverative
      error scores on the Wisconsin Card Sort Test in arsonists, which could not be
      accounted for by state anxiety or depression scores.

PMID- 11848140
TI  - Psychiatric probation orders: failed provision or future panacea?
AB  - The psychiatric probation order has been a sentencing option for the courts for
      over fifty years. Many authors have lamented its underuse and described the
      inability of psychiatric and probation services to work together in a
      collaborative and effective way. The aim of this study was to describe
      probationers who had passed through Elliott House, a specialist bail and
      probation hostel for mentally disordered offenders. A retrospective case note
      review of all individuals who have been resident at Elliott House as a condition
      of a probation order was conducted. The individuals were mostly young, single men
      with a severe mental illness and comorbid substance misuse. As a group their
      previous contact with psychiatric services was irregular. A probation order at
      Elliott House appeared to provide social support and stability along with a
      period of regular psychiatric treatment and follow-up. The results suggest that
      psychiatric probation orders, if properly managed, can be a useful tool for both
      health and probation services in the short term.

PMID- 11848141
TI  - Audit of the Forensic Psychiatry Liaison Service to Glasgow Sheriff Court 1994 to
      1998.
AB  - This study seeks to describe the demographic, offence, and diagnostic details of
      subjects referred by the Procurator Fiscal at Glasgow Sheriff Court to the
      Forensic Psychiatry Liaison between 1994 and 1997. The initial outcome of the
      assessment and an assessment of medical time involved is presented. This study is
      a retrospective review of audit forms completed between 1993 and 1994 and once
      more in 1997. The referral criteria, age structure and offence pattern was
      broadly similar to that reported in court diversion schemes in England. A primary
      diagnosis of alcohol and/or drug dependence was seen in one third of referrals
      during both years of the audit. A marked increase (250%) in referrals between
      1994 and 1997 resulted in a marked reduction of those admitted to hospital, and
      an increase in the percentage who had 'no psychiatric diagnosis'. The need for
      ongoing liaison between the Procurators Fiscal and the Forensic Psychiatrists
      involved would appear important in modifying referral criteria.

PMID- 11848142
TI  - Medico-legal reports and gatekeeping: one year of referrals to a forensic
      service.
AB  - Forensic psychiatrists and the services they provide have been subject to recent
      scrutiny and high public profile. This study examined part of the work of a
      regional and district forensic service by looking at a one-year cohort of
      referrals, and the factors contributing to patient admission, including requests
      for medico-legal reports. The sample consisted of all referrals to the East
      Midlands Centre for Forensic Mental Health, Leicester from 1 January 1998 to 31
      December 1998. Information on referrals was collected retrospectively using a
      proforma to collate data from referral letters and the reports prepared by
      assessing clinicians. Two hundred and eighty referrals relating to 260
      individuals were received. The sample characteristics were broadly similar to
      those reported in previous studies. The finding that 70% of those assessed were
      referred for medico-legal reports by courts or solicitors, and the fact that only
      20% of this group finally entered the forensic service, led us to consider
      whether this work was legitimate use of National Health Service time. We examined
      this group more closely, and found that referral for a medico-legal report could
      be considered as a screening test for entry into the forensic services and there
      are good arguments for this work continuing.

PMID- 11848143
TI  - Crime and Punishment (Scotland) Act 1997: a survey of sentencers' views
      concerning the Scottish 'hybrid order'.
AB  - The Crime and Punishment (Scotland) Act 1997 introduced the hospital direction
      (HD), often termed the 'hybrid order' because it allows courts to simultaneously
      send a mentally disordered offender to hospital and impose a prison sentence, to
      be completed after hospital discharge. It is the first measure that explicitly
      allows the imposition of a prison sentence for an offender meeting criteria for
      detention under the Mental Health (Scotland) Act 1984. A previous survey showed
      that psychiatrists in Scotland favoured the principle of a hybrid order (Darjee
      et al., 2000). In this study all Scottish Sheriffs (n = 110) and High Court
      Judges (n = 26) were surveyed for their views on the HD. Of the 56 respondents 19
      felt unable to participate largely due to lack of experience in sentencing
      mentally disordered offenders. Respondents felt the HD was a useful measure, but,
      in contrast to Scottish Office guidance, indicated that psychiatrists should
      recommend it directly if they considered that it was an appropriate disposal.
      Respondents viewed the HD as primarily an incapacitating measure and most
      respondents hoped that it would encourage psychiatrists to admit 'psychopaths';
      although Scottish psychiatrists do not favour the hospitalisation of offenders
      with primary personality disorders. It is concluded that in its current form and
      with current guidance the HD is difficult to use, as there are no criteria to
      differentiate it from a hospital order (HO) and psychiatrists cannot recommend
      it. Further, recent legislation that makes public safety the primary concern when
      deciding on the discharge of restricted patients in Scotland, erodes the utility
      of the HD as an incapacitating measure. However following the Reports of the
      Millan and MacLean Committees in Scotland, the role of the HD may be strengthened
      and clarified.

PMID- 11848144
TI  - Fatal self-harm in the elderly.

PMID- 11848145
TI  - Patient's rights under extended Section 2 of the Mental Health Act 1983.

PMID- 11848146
TI  - Legal definition of a wound.

PMID- 11848148
TI  - A rapid method for 90Sr determination in the presence of 137Cs in environmental
      samples.
AB  - A rapid method for the determination of 90Sr in the presence of 137Cs using the
      Cherenkov radiation technique is described. The contribution of 137Cs to gross
      Cherenkov radiation (90Y + 137Cs) was examined for 137Cs /90Sr ratios ranging
      from 0.09 to 2.50 for 137Cs activities ranging from 2 to 1,211 Bq. Results from
      direct Cherenkov radiation measurement and results after radiochemical separation
      of 90Y from 90Sr for samples containing both 90Sr and 137Cs were compared. Errors
      below 5% were obtained for 137Cs /90Sr ratios lower than 1, when no separation
      was performed, independently of the activity level. However, errors between 10%
      and 35% were obtained for 137Cs/90Sr ratios higher than 1. In order to determine
      90Sr activity in the presence of 137Cs using the Cherenkov technique, a multiple
      linear regression analysis model was established to correct the data for 137Cs
      content. The mathematical correction proposed was validated using 66 artificially
      contaminated lettuce samples in a laboratory experiment by taking into account
      the activity levels of 137Cs and 90Sr and the radionuclide ratios. Comparison of
      mathematically corrected radionuclide ratios with the results obtained without
      correction shows that, for radionuclide ratios higher than 1, error values for
      measuring 90Sr activity using the mathematical model were much smaller than when
      no radiochemical separation was performed. On the other hand, for ratios lower
      than 1, error values when measuring 90Sr activity with radiochemical separation
      were smaller than when mathematical correction was performed. In spite of this,
      the mathematical correction is an appropriate way of reducing the time needed to
      determine radiostrontium using the Cherenkov radiation technique. The method
      proposed could be a powerful tool for environmental research whenever the
      contents of 90Sr and 137Cs have to be determined.

PMID- 11848147
TI  - Distribution of 90Sr in coastal seawater, sediments and organisms off two atomic
      power stations in Korea.
AB  - We have measured 90Sr activities in the marine environment (seawater, sediments
      and organisms) off the two Korean atomic power stations at Gori and Weolseong.
      The marine sampling sites were chosen in the vicinity of the power stations to
      investigate the dispersion of any local 90Sr sources. The 90Sr activities in
      seawater ranged from 1.3 to 1.9 mBq/l (mean: 1.4, n = 16) and 0.9 to 1.5 mBq/l
      (mean: 1.3, n = 29) at the Gori and Weolseong sites, respectively. These
      activities are comparable with those reported for the remote open ocean,
      suggesting that the 90Sr at these sites originated primarily from global fallout,
      which occurred during the 1960s, rather than from any local sources. The 90Sr
      activities in marine sediments ranged from 116 to 1,277 mBq/kg (mean: 565, n =
      12) and from 304 to 1,799 mBq/kg (mean 933, n = 6) at the Gori and Weolseong
      sites, respectively. The horizontal distribution of 90Sr in surface sediments
      appears to be affected by grain size as well as local sedimentation rate. The
      enrichment of 90Sr in fish (5.5 +/- 2.6 mBq/kg, n = 5) and shellfish (7.1 +/- 1.2
      mBq/kg, n = 2) was much lower than that in seaweed (57 +/- 33 mBq/kg, n = 5).

PMID- 11848150
TI  - Assessing potential risks from exposure to natural uranium in well water.
AB  - Over 50% of the wells in the Nambe region of northern New Mexico exceed the US
      Environmental Protection Agency's recommended drinking water standard of 20
      microg l(-1) for 238U; the highest in the area was measured at 1,200 microg U l(
      1). Uranium uptake was estimated in tomato (Lycopersicon esculentum), squash
      (Cucurbita pepo), lettuce (Lactuca scarriola), and radish (Raphanus sativus)
      irrigated with Nambe well water containing <1, 150, 500, and 1,200 microg U l(
      1). Plant uptake and human dose and toxicity associated with ingestion of water
      and produce and inhalation of irrigated soil related to gardening activities were
      evaluated. Uranium concentration in plants increased linearly with increasing U
      concentration in irrigation water, particularly in lettuce and radish. The
      estimated total committed effective dose for 70 years of maximum continuous
      exposure, via the three pathways to well water containing 1,200 microg U l(-1),
      was 0.17 mSv with a corresponding kidney concentration of 0.8 microg U g(-1)
      kidney.

PMID- 11848149
TI  - The cost-effectiveness of residential radon remediation programmes: assumptions
      about benefits stream profiles over time.
AB  - A recent cost-effectiveness analysis of a residential radon remediation programme
      considered and highlighted many areas of uncertainty in the parameters chosen for
      the analysis. One assumption not challenged in the study was the benefits stream
      profile adopted. There are several different ways of loading the benefits in
      terms of life years into the cost-effectiveness model and several of these are
      explored and the results are reported in this study. The benefits profile depends
      upon the lead-time to cancer manifestation post environmental carcinogen (radon)
      exposure. The literature reviewed suggests that there are many options for
      loading benefits to radon-induced lung cancer prevention programmes. In this
      study, the alternative benefits stream profiles are explored and their
      implications for the cost-effectiveness ratio are examined. Adopting different
      benefits stream profiles to the model results in a range of cost-effectiveness
      ratios from 14912.90 pounds per life year gained to 52416.27 pounds per life year
      gained. The preferred model is reported where the life years gained are assumed
      to be equally distributed over the last 15 years of the 40-year time horizon of
      the analysis (Y25-40) and the corresponding cost-effectiveness ratio is 37,943
      pounds per life year gained.

PMID- 11848151
TI  - Distribution and mobilization of U, Th and 226Ra in the plant-soil compartments
      of a mineralized uranium area in south-west Spain.
AB  - The activity concentrations of natural uranium isotopes (238U and 234U), thorium
      isotopes (232Th, 230Th and 225Th) and 226Ra were studied in soil and vegetation
      samples from a disused uranium mine located in the Extremadura region in the
      south-west of Spain. The results allowed us to characterize radiologically the
      area close to the installation and one affected zone was clearly manifest as
      being dependent on the direction of the surface water flow from the mine. The
      activity concentration mean values (Bq/kg) in this zone were: 10,924, 10,900,
      10,075 and 5,289 for 238U, 234U, 230Th and 226Ra, respectively, in soil samples
      and 1,050, 1,060, 768 and 1,141 for the same radionuclides in plant samples. In
      an unaffected zone, the activity concentration mean values (Bq/kg) were: 184,
      190, 234 and 7251 for 235U, 234U, 230Th and 226Ra, respectively, in soil samples
      and 28. 29, 31 and 80 in plant samples. The activity concentrations obtained for
      232Th and 228Th showed that the influence of the mine was only important for the
      uranium series radionuclides. The relative radionuclide mobilities were
      determined from the activity ratios. Correlations between radionuclide activity
      concentrations and stable element concentrations in the soil samples helped to
      understand the possible distribution paths for the natural radionuclides.

PMID- 11848152
TI  - Concentration of caesium-137, cobalt-60 and potassium-40 in some wild and edible
      plants around the nuclear power plant in Bulgaria.
AB  - The activities of 137Cs, 60Co and 40K were determined in samples of wild
      (Taraxacum officinale, Plantago lanceolata and Populus nigra 'Italica') and
      edible (vegetable, corn, fruit) plants as well as soil collected from the 30 km
      safety zone of the Bulgarian NPP "Kozloduy" and comparisons with earlier
      measurements and analyses of samples from other regions and with literature
      values were performed. The derived transfer factors for 137Cs and 40K from soil
      to plants ranged between 0.002 and 0.009 for 137Cs, and between 0.09 and 0.35 for
      40K. The individual effective dose (calculated from the present results and data
      on the activity of other foodstuffs and from information about dietary habits)
      comprises 4.5% of the annual dose limit.

PMID- 11848153
TI  - Distributions of Pu, Am and Cs in margin sediments from the western Mediterranean
      (Spanish coast).
AB  - Continental margins are important areas to be considered when studying the
      distributions and depositions of pollutants, both conventional and radioactive.
      Coastal sediments accumulate most of those contaminants which can be introduced
      following atmospheric and/or fluvial pathways. Moreover, their residence times
      within the water column are usually shortened due to their affinity to associate
      with the downward falling particulate matter, more abundant at shallower depths.
      In this paper the distribution profiles and inventories of plutonium, americium
      and cesium are detailed, providing useful information about recent sedimentation
      phenomena such as sediment mixing, slumping processes and bioturbation.
      Unsupported 210Pb data are used as reliable indicators of enhanced/reduced
      deposition events. Also, the calculated inventories have enabled the estimation
      of the radiological contribution of the Spanish Mediterranean margin to the total
      radioactivity deposited onto the Mediterranean sea floor.

PMID- 11848154
TI  - 226Ra/238U disequilibrium in an upland organic soil exhibiting elevated natural
      radioactivity.
AB  - This paper presents the results of a study into the anomalous 226Ra/238U
      disequilibrium (226Ra/238U of 0.5-9) exhibited by an upland organic soil in Co.
      Donegal, Ireland. Radiochemical speciation of 226Ra, 238U and 225Ra indicates
      that in this organic soil the high 226Ra/238U ratio is due to loss of 235U
      relative to 226Ra via oxidation and mobilisation of 238U in the upper layers of
      the soil and subsequent loss in solution. At the lower, more reducing depths of
      the soil profile, 238U and 226Ra are essentially in equilibrium. Loss of 238U
      appears to occur primarily from the easily oxidised organic and iron oxide
      fractions of the soil, samples exhibiting high 226Ra/238U ratios displaying
      significantly lower 238U levels in these fractions than samples whose ratio is
      below the average value for the soil of the valley. Selective enrichment of 226Ra
      by plants or preferential leaching of 226Ra from the underlying rock is not
      supported by the results of this study.

PMID- 11848155
TI  - Personality factors and drug of choice in female addicts with psychiatric
      comorbidity.
AB  - Female addicts (N= 108) with a mean age of 37.2 were tested using the Temperament
      and Character Inventory (TCI) in 1996-97. In a representative sub-sample (N = 49)
      assessed with the Structured Clinical Interview. DSMIIIr (SCID), 82% manifested
      an axis-1-syndrome (lifetime), and 53% a personality disorder. Of the 108
      addicts, 42 preferred alcohol, 14 heroin, 33 amphetamines, and 19
      benzodiazepines. Maturity was low, but there were no differences in maturity
      between drug preference groups. Results indicated that those less mature were
      more "novelty-seeking" and "harm-avoidant", while those maturer tended to be more
      persistent. Less mature persons answered less consistently. They agreed more with
      different items and their answers were more rare when compared to the general
      population. Heroin addicts were less sentimental and helpful and more aware of
      their own resources. Benzodiazepine and amphetamine addicts were more self
      transcendent and self-forgetful. Among the relatively more mature, benzodiazepine
      addicts scored higher than heroin and alcohol addicts on "true" and rare answers.
      In conclusion, maturity and the drug of choice among female addicts were related
      to different TCI scales.

PMID- 11848156
TI  - The role of drugs in crime: insights from a group of incoming prisoners.
AB  - The present study was designed to evaluate whether drug dependence is associated
      with any specific perception of the role of drugs in crime. In the summers of
      1997 and 1998, face-to-face interviews were conducted with members of a group of
      incoming prisoners at the Cuyahoga County Jail in Cleveland. Ohio. "Incoming
      prisoners" denotes persons whose criminal cases had been adjudicated and who were
      of their way to one of Ohio's prisons. Respondents were asked whether they
      themselves perceived that drugs had been a factor in the crimes for which they
      had been arrested. Those respondents classified as dependent on at least one
      illicit drug tended to answer affirmatively. This sub-group was also more likely
      than their non-dependent counterparts to admit to using drugs in the two days
      following the commission of their crimes. Specifically, these respondents viewed
      the need to obtain drugs for personal use as one of their main motives for
      participating in crime.

PMID- 11848157
TI  - Drinking in the injury event: a comparison of Mexican-American male ER patients
      in the United States and in Mexico.
AB  - Probability samples of 66 Mexican-American injured male emergency room (ER)
      patients in Santa Clara County, CA, and 457 injured male ER patients in Pachuca,
      Mexico are compared on a number of drinking-in-the-event variables. While those
      in Pachuca were more likely to be positive on the breathalyzer than those in
      Santa Clara, they were less likely to attribute a causal association of their
      drinking with the event. Site (Santa Clara) was found to be a significant
      (positive) predictor of drinking prior to injury.

PMID- 11848159
TI  - Drugs in prison: a break in the pathway.
AB  - The use of psychoactive substances by offenders is a major preoccupation among
      correctional network clinicians, researchers and administrators. However, very
      little is known about this phenomenon during incarceration. The research
      presented here explores patterns of inmate drug use during imprisonment. Selected
      at random, 317 respondents in 10 Canadian penitentiaries were interviewed in 1999
      to complete self-reported questionnaires. The data indicate various types of
      important changes, notably with regard to substances used, frequency of use,
      motivations for use, and inmates' perception of their psychological state during
      periods of intoxication.

PMID- 11848158
TI  - Correlates of treatment follow-up difficulty.
AB  - This study examines the correlates of treatment follow-up difficulty utilizing
      data from the District of Columbia Treatment Initiative (DCI). Findings indicate
      that (1) treatment completion is positively associated with a successful follow
      up; (2) age and number of prior arrests are related to follow-up difficulty; (3)
      persons easiest to reach were more likely to be employed at follow-up; (4)
      persons difficult to locate were more likely to be using cocaine and to be
      arrested post-discharge; and (5) cocaine use at follow-up might be underestimated
      and employment at follow-up might be overestimated in findings derived from less
      than 80% of the target sample.

PMID- 11848160
TI  - Gender and intergenerational transmission of alcohol use patterns: an analysis of
      adult children in Moscow.
AB  - Based on a 1996 sample of adult children and their parents in Moscow, this study
      investigates the degree to which alcohol use patterns are transmitted from
      parents to adult children and examines the roles of gender, family status, and
      family interaction dynamics for transmission. Findings suggest that parents'
      drinking and family status/interaction patterns indeed influence adult children's
      alcohol consumption. Frequency and volume of alcohol use is higher among children
      whose mothers typically drink about 3 or more drinks daily or who drink on a
      weekly basis. Fathers' frequency and volume of alcohol use positively influences
      only sons' drinking. Mothers' drinking, however, may undermine fathers' positive
      effect on sons. Fathers' verbal and physical abuse significantly affects
      daughters' consumption.

PMID- 11848162
TI  - Effect of age on chronological variation of acute myocardial infarction onset:
      study in Japan.
AB  - To evaluate the effect of age on circadian and seasonal variation in the onset of
      acute myocardial infarction (AMI) in Japan, we studied 725 patients whose onset
      date and time of the symptom were determined. In the analysis of all AMI
      patients, the occurrence showed significant circadian variation (P< 0.01); 30% of
      episodes occurred between 0600 and 1200h which formed a dominant morning peak. In
      the analysis of separate age-groups, a significant difference in the occurrence
      among four 6-hour periods of day was observed only in the early-elderly group (65
      74 years), in which a significant (P < 0.01) morning peak comprising 33% of
      episodes was observed between 0600 and 1200 h. The monthly variation of AMI onset
      in total subjects tended to show two peaks; April and August. The seasonal
      variation tended to show a trough in autumn when analyzed in all patients, but
      the variation was significant only in middle-aged group (< 65 years). In
      conclusion, the incidence of AMI in Japanese population showed dominant morning
      peak, and tended to show autumn trough. These circadian and seasonal variations
      were affected by age.

PMID- 11848161
TI  - Assessing the diversity of personal beliefs about addiction: development of the
      addiction belief inventory.
AB  - Previous work in the field of substance use/misuse has suggested that client
      beliefs about addiction are quite diverse, and may influence the effectiveness of
      various treatment approaches. This paper presents an Addiction Belief Inventory
      (ABI) that was developed and evaluated to assess personal beliefs about addiction
      and substance use problems. The ABI is a 40-item instrument developed using two
      clinical samples: an alcohol user treatment group (N = 134) and a dual diagnosis
      treatment group (N = 536). Confirmatory factor analysis revealed seven stable
      subscales: inability to control, chronic disease, reliance on experts,
      responsibility for actions, responsibility for recovery, genetic basis, and
      coping. Multivariate analyses provided preliminary reliability and validational
      support. The utility of the ABI for clinical and research purposes is discussed,
      along with suggestions for future research and improvements to the instrument.

PMID- 11848163
TI  - Circadian variation of blood pressure and neurohumoral factors during the acute
      phase of stroke.
AB  - This study was to investigate the relationship between circadian blood pressure
      (BP) variation and circadian variation of neurohumoral factors during the acute
      phase of stroke. We studied 17 patients with cerebral infarction in 16 and
      cerebral hemorrhage in one. We performed 24-hour ambulatory BP monitoring and
      examined plasma renin activity (PRA), catecholamine, atrial natriuretic peptide
      (ANP), brain natriuretic peptide (BNP), endothelin 1 (ET1) and prothrombin
      fragment 1+2 (PT F1+2) and urinary catecholamine. Our result showed that the
      circadian variation of BP, neurohumoral and coagulation factors were diminished.
      There were significant relationships between BP levels and plasma BNP levels,
      nocturnal urinary adrenalines and ET1s. There were also significant relationships
      between night/day ratio of BP and plasma ET1 level. In conclusion the abnormal
      patterns of circadian BP rhythm were frequently observed during the acute phase
      of stroke. The cause of this abnormality may result from the diminished circadian
      rhythms of neurohumoral factors.

PMID- 11848164
TI  - Correlation of Lorenz scatterplots with frequency-domain heart rate variability.
AB  - Heart rate (HR) variability is important with respect to disease prognosis and
      the effects of drugs. Lorenz scatterplots provide a simple way to evaluate HR
      variability visually. The relation of Lorenz scatterplots to frequency-domain HR
      variability was examined in 75 Holter recordings and in simulated HR trends. The
      length of Lorenz scatterplots was double-exponentially correlated with total
      frequency and very-low frequency powers, with correlation coefficients (r) of
      0.88. The width of Lorenz scatterplots was highly correlated with the high
      frequency power (r=0.98). The sum of the width and length of Lorenz scatterplots
      was highly correlated with the total frequency power (r=0.92). Identical results
      were obtained when simulated HR trends were used. In conclusion, Lorenz
      scatterplots provide a simple way to estimate the frequency-domain HR
      variability.

PMID- 11848165
TI  - Relationship between personality and self-measured blood pressure value at home:
      the Ohasama study.
AB  - We conducted a cross-sectional community survey in northern Japan to assess the
      relationship between personality and home blood pressure value. The Japanese
      version of the short-form Eysenck personality questionnaire was used to assess
      personality. A total of 999 people selected from the general population
      participated. We showed that the personality extroversion score positively
      affected the systolic blood pressure value, whereas no significant relationship
      was observed between personality psychoticism or neuroticism and blood pressure
      value. This study is the first to clarify the relationship between personality
      assessed by the Eysenck personality questionnaire and blood pressure measured in
      a non-medical setting. When physicians investigate the pathogenesis of essential
      hypertension, they should take psychological factors into consideration, as well
      as the many environmental and genetic factors.

PMID- 11848166
TI  - The effects of postural changes of baroreflex gain in normal and hypertensive
      pregnancies.
AB  - In order to understand the changes of baroreflex gain due to postural changes in
      normal pregnancies, we measured percentage changes (% changes) in blood pressure
      (SBP, DBP), heart rate (HR), stroke volume (SV), cardiac output (CO), total
      peripheral resistance (TPR) as well as cardiac autonomic nervous function (HF as
      an index of parasympathetic and LF/HF as an index of sympathetic function) and
      compared these parameters in normal pregnancies with those found in hypertensive
      pregnancies, such as chronic hypertensive (CHP) and severe preeclamptic
      pregnancies (PE), in late pregnancy (after 32 wks). When the position was changed
      from supine to standing in normal and non-pregnant women, the % changes of HR,
      DBP, TPR and LF/HF were increased and SBP, SV, CO and HF were decreased. The %
      changes of these parameters, however, were gradually decreased as pregnancy
      progressed, especially after 20-24 wks of gestation. In hypertensive pregnancies,
      however, even in late pregnancy, the decreased SBP and increased TPR was still
      observed and the profound decrease of CO and SV and increase of TPR were
      characteristic in PE when compared to CHP.

PMID- 11848167
TI  - Effects of alcohol consumption and restriction on home blood pressure in
      hypertensive patients: serial changes in the morning and evening records.
AB  - To study the time course of alcohol effects on blood pressure (BP), we examined
      morning and late evening home BP for 4 weeks in a regular alcohol consumption
      period and for 4 weeks in a alcohol restriction period in 30 Japanese men with
      essential hypertension (52 +/- 2 years, m +/- SE) in a randomized crossover
      study. Mean daily intake of alcohol were 66.5 +/- 4.7 and 10.2 +/- 1.9 ml,
      respectively. At the end of the regular alcohol period, morning BP had increased
      by 4.4 +/- 1.1/2.9 +/- 0.8 mmHg but evening BP had decreased by 7.4 +/- 1.9/5.7
      +/- 1.7 mmHg. The depressor effect of alcohol on the evening BP was evident from
      day 1 to week 4, while the pressor effect on the morning BP was significant from
      week 2 regardless of the order of the two periods. These results confirm the
      biphasic effect of alcohol on BP, and suggest that the status of alcohol intake
      may markedly influence the morning-evening BP difference.

PMID- 11848168
TI  - Comparison of the effects of amlodipine and losartan on 24-hour ambulatory blood
      pressure in hypertensive patients.
AB  - Effects of amlodipine (AML), a long-acting calcium antagonist, and losartan
      (LOS), an angiotensin II receptor antagonist, on 24-hr blood pressure profile
      were compared in 15 patients with essential hypertension. After 4 weeks of
      placebo period, the patients were treated with AML or LOS in a random crossover
      design for 12-16 weeks each. Either drug was given once daily at 0800 and the
      doses were titrated so that the office blood pressure was reduced lower than
      140/90mmHg. At the end of each period, 24-hr blood pressure was monitored.
      Average office blood pressure was lowered from 158 +/- 2/ 98 +/- 2 mmHg to 134 +/
      1/87 +/- 1 mmHg by AML and 134 +/- 2/88 +/- 1 mmHg by LOS. Average 24-hr blood
      pressure was also reduced from 144 +/- 3/ 92 +/- 2 mmHg to 131 +/- 2/84 +/- 2
      mmHg by AML and 135 +/- 3/85 +/- 2 mmHg by LOS. The averaged 24-hr systolic blood
      pressure was significantly lower in AML than in LOS (p < 0.05). Then, the 24-hr
      blood pressure was analyzed for four segments; morning (0530-0900 h), daytime
      (0930-1800 h), evening (1830-2300 h) and night (2330-0500 h). Although the
      daytime blood pressure was comparable between AML and LOS, systolic blood
      pressure in the evening and morning hours were lower in AML than in LOS (133 +/-
      2 vs. 138 +/- 3mmHg,p<0.01; 129 +/- 3 vs. 134 +/- 4,p<0.05). Troughtopeakratio of
      antihypertensive effect on systolic blood pressure was significantly greater in
      AML than in LOS (62 +/- 5% vs. 55 +/- 4%, p < 0.05). Either drug did not cause
      reflective increase in pulse rate over 24 hours. These results suggest that both
      AML and LOS are equally effective in lowering daytime blood pressure without
      eliciting reflex tachycardia, however, the antihypertensive effect of AML lasts
      longer than that of LOS. Such information seems important to achieve 24-hr blood
      pressure control using these drugs.

PMID- 11848169
TI  - Blood pressure reduction in the morning yields beneficial effects on progression
      of chronic renal insufficiency with regression of left ventricular hypertrophy.
AB  - Self-monitoring values of blood pressure may better reflect the average long-term
      blood pressure value than sporadic measurements in the physician's office and be
      more useful for blood pressure control. In the present study, we compared the
      results of self-monitoring of blood pressure values, especially in the morning,
      with office blood pressure, and related these to progression of chronic renal
      insufficiency and left ventricular hypertrophy (LVH). Thirty-four patients were
      selected from 316 subjects with chronic renal insufficiency (average serum
      creatinine 1.72 +/- 0.15 mg/dl, mean age 52.6 +/- 3.5 yrs) in accordance with the
      following criteria (1) office blood pressure was less than 140/90 mmHg, (2) blood
      pressure was controlled with amlodipine (5-20 mg/day) combined with benazepril
      (2.5 mg/day), (3) morning blood pressure was greater than 150/90 mmHg at 6-9 AM
      and (4) LVH had been determined by echocardiography (posterior wall thickness;
      PWT > or = 12 mm). The patients were assigned to 2 groups at random and were
      given: (1) guanabenz (GB; 2-8 mg at I I PM, n = 17) or (2) placebo (n = 17). Two
      years later, the average blood pressure of both groups as measured in the office
      was not significantly different: however, BP in the morning was significantly
      reduced from 158 +/- 6 to 134 +/- 4 mmHg in GB treated group (P< 0.001). In 14 of
      17 patients in GB treated group, LVH resolved and there was only mild progression
      of nephropathy (serum creatinine: 1.69 +/- 0.18 to 1.81 +/- 0.19 mg/dl). In 12 of
      14 patients in placebo group, whose morning blood pressure remained at greater
      than 150/90 mmHg, LVH was retained and there was moderate progression of
      nephropathy (serum creatinine: 1.73 +/- 0.14 to 2.62 +/- 0.50mg/dl). From these
      results, it is suggested that antihypertensive treatment with combination therapy
      based on self-monitoring BP is cardio-renoprotective in patients with chronic
      renal insufficiency and LVH.

PMID- 11848171
TI  - Heart rate variability in congestive heart failure.

PMID- 11848170
TI  - Insulin resistance is associated with reduced nocturnal falls of blood pressure
      in normotensive, nonobese type 2 diabetic subjects.
AB  - To assess the relationship between insulin resistance and ambulatory blood
      pressure (BP) pattern, we determined glucose infusion rate (GIR) as a marker of
      insulin resistance using a glucose clamp method, and measured 24-h BPs in 25
      normotensive, nonobese type 2 diabetic subjects. They were divided into two
      groups: 11 dippers and 14 nondippers. Clinical characteristics were similar in
      the two groups except for orthostatic fall in systolic BP. The median GIR level
      was significantly lower in nondippers than in dippers (P < 0.05). Spearman's rank
      correlation revealed that the GIRs were negatively correlated with the systolic,
      diastolic and mean BPs during nighttime (P < 0.05 or less), but not with daytime
      or whole day BPs. Moreover, based on a logistic regression analysis, the GIR as
      well as orthostatic fall in systolic BP discriminated independently between
      dippers and nondippers. Thus, our results suggest that insulin resistance is
      associated with decreased nocturnal BP fall in type 2 diabetic subjects.

PMID- 11848172
TI  - Heart rate variability in normotensive healthy children with aging.
AB  - Although the heart rate variability (HRV) values in adults decrease with aging,
      those in children show a variety of changes. The present study was designed to
      investigate the relationship between HRV and aging, physique and blood pressure
      in 70 healthy male school children, between 6 and 12 years of age. The subjects
      were divided into 3 age groups (6-7, 8-9 and 10-12 years) and 3 other groups
      according to physique (thin, under -10%; normal, -10-20% and obese, over 20% of
      obesity index). After recording a 24-h ambulatory electrocardiograph, HRV was
      determined spectrally, using 3 components: the total-frequency (TF) component
      (0.01 to 0.5 Hz), the low-frequency (LF) component (0.04 to 0.15 Hz), the high
      frequency (HF) component (0.15 to 0.5 Hz) and also a two component ratio (LF/HF).
      The HRV values between the 3 age groups had a significant effect on TF, LF and
      LF/HF during the 24-h period, with the values increasing with age. The HRV values
      between the 3 physique groups had no significant effect. Therefore, changes in
      HRV in school children are affected by age and not physique. It is possible that
      the increase in HRV values with age is caused by the development of the autonomic
      nervous system.

PMID- 11848173
TI  - Prognostic significance of heart rate variability in centenarians.
AB  - We studied the significance for further survival of heart rate variability and
      other variables in the very elderly. In 1992, we assessed activities of daily
      living, cognitive function, and nutritional status in 27 centenarians with no
      disease, in addition to the power of the heart rate variability in the ultralow,
      very low, low (LF), and high frequency (HF) bands. In 1996, we assessed survival
      in these centenarians; 17 had died and 10 were still living. Logistic regression
      analysis using backward elimination detected three factors, dementia, LF/HF, and
      age, that independently influenced mortality. Mortality risk increased with
      greater age in 1992, more severe dementia, or lower LF/HF. Sympathetic nerve
      activity, represented as LF/HF, may be associated with prognosis for survival in
      centenarians.

PMID- 11848174
TI  - Does sodium sensitivity affect nocturnal blood pressure variation in outpatients
      with hypertension?
AB  - We investigated the relationship between sodium sensitivity and diurnal variation
      of blood pressure in outpatients with hypertension. Twenty hypertensives were
      maintained on both a regular sodium diet for a period of 2 weeks and a low salt
      (7 g/day) diet for a period of one or two weeks. Ambulatory blood pressure was
      recorded at thirty minute intervals for 24 hours by automatic device before and
      during low salt diet. Patients were classified by nocturnal fall in blood
      pressure. 14 patients were classified as sodium sensitive, whereas 6 were
      classified as non-sodium sensitive on the basis of a > or = 0 in salt sensitive
      index caused by sodium restriction. Incidence of reversed dipper and non-dipper
      in systolic blood pressure was reduced by sodium restriction, however, dipper and
      extreme dipper were increased. In conclusion, the results of this study show that
      patients with high sodium sensitivity index have strong sodium sensitivity and
      non-dipper is not always changed by sodium restriction.

PMID- 11848175
TI  - Assessing service quality in paediatric audiology and early deaf education.
AB  - Quality monitoring and assurance is a key aspect of evidence-based service
      provision in health and education. Part I of the present paper summarizes the
      results from a survey in which performance of health-based paediatric audiology
      services in the UK was assessed against existing good practice guidelines (NDCS,
      1994, 1996). The results of the survey indicated varied levels of provision, with
      guidelines commonly not followed. Part II of the paper reports the detailed
      development of two short questionnaires designed to provide scores (out of 100)
      reflecting aspects of service quality in paediatric audiology services and in
      early deaf education services. The results from the use of the two indices (the
      Paediatric Audiology Service Index (PASI) and the Deaf Education Early Service
      Index (DEESI)) are presented along with data from some component questions.
      Although some services are functioning close to guideline levels of service, the
      overall distribution of scores is such as to raise serious concerns about the
      variability of quality and the consequent inequity of provision for children with
      permanent hearing loss and their families in both health and education services.

PMID- 11848176
TI  - Comparison of three procedures for initial fitting of compression hearing aids.
      I. Experienced users, fitted bilaterally.
AB  - We compared the effectiveness of three procedures for the initial fitting of
      hearing aids with multi-band compression: (1) CAMEQ, which aims to amplify speech
      so as to give equal loudness per critical band over the frequency range important
      for speech intelligibility, and to give similar overall loudness to 'normal': (2)
      CAMREST, which aims to amplify speech so as to restore 'normal' specific loudness
      patterns, over a wide range of speech levels; (3) DSL I/O, which aims to map the
      dynamic range of normally hearing people into the reduced dynamic range of
      hearing-impaired people, with 'full' restoration of audibility. Ten experienced
      hearing aid users with moderate sensorineural loss were fitted bilaterally with
      Danalogic 163D digital hearing aids, using each procedure in turn; the order was
      counterbalanced across subjects. The fitting required specification of gains for
      input levels of 55 and 80 dB SPL at six centre frequencies. Real-ear measurements
      were made to ensure that target gains were reached (+/-3 dB). Immediately after
      fitting with a given procedure, and one week after fitting, the gains were
      adjusted when required by the minimum amount necessary to achieve acceptable
      fittings. The amount of adjustment required provides one measure of the adequacy
      of the initial fitting. On average, the adjustments were smallest for the CAMEQ
      procedure. The gain changes were slightly larger for the CAMREST procedure and
      were largest of all for DSL I/O. For the latter, the gain changes were mostly
      negative, especially for high frequencies and the higher input level. This
      indicates that the DSL I/O procedure prescribes more high-frequency gain than is
      preferred by adult users. After these gain adjustments, users wore the aids for
      at least three weeks before filling out the APHAB questionnaire and taking part
      in laboratory measurements of the speech reception threshold (SRT) for sentences
      in quiet and in steady and fluctuating background noise at levels of 60 and 75 dB
      SPL. Following these tests, the hearing aids were re-fitted with the next
      procedure. The scores on the APHAB test and the SRTs did not differ significantly
      for the three procedures. We conclude that the CAMEQ and CAMREST procedures
      provide more appropriate initial fittings than DSL I/O.

PMID- 11848177
TI  - Measurement of first- and second-order modulation detection thresholds in
      listeners with cochlear hearing loss.
AB  - First- and second-order modulation detection thresholds were measured in normal
      hearing and hearing-impaired listeners. 'First-order' modulation detection
      thresholds correspond to the ability of listeners to detect sinusoidal amplitude
      modulation (SAM); they are measured as a function of the frequency of that
      modulation, f(m). 'Second-order' modulation detection thresholds correspond to
      the ability to detect sinusoidal modulation applied to the modulation depth of a
      SAM signal; they are measured as a function of the frequency of the modulation
      applied to the modulation depth (referred to as f(m)'). In this case, the SAM
      signal acts as a 'carrier' stimulus of frequency f(m) and sinusoidal modulation
      of the SAM-signal's modulation depth (at rate f(m)') generates two additional
      components in the modulation spectrum at f(m)-f(m)' and f(m)+f(m)'. In both
      groups of listeners, first-order modulation detection thresholds were measured
      for modulation frequencies f(m) ranging between 4 Hz and 32 Hz, and second-order
      modulation detection thresholds were measured for second-order modulation
      frequencies f(m)' ranging between 1 Hz and 11 Hz, using a fixed first-order
      modulation frequency f(m) of 16 Hz. The results showed that, in hearing-impaired
      listeners: first-order modulation detection thresholds were within the normal
      range up to f(m) = 16 Hz and poorer than normal at f(m) = 32 Hz; second-order
      modulation detection thresholds were within the normal range at f(m)' = 3, 5 and
      11 Hz, and poorer than normal at f(m)' = 1 Hz and 7 Hz. These results suggest
      that cochlear damage has little effect on the detection of both sinusoidal and
      complex temporal envelopes.

PMID- 11848178
TI  - Effects of slow- and fast-acting compression on the detection of gaps in narrow
      bands of noise.
AB  - The inherent amplitude fluctuations in narrow bands of noise may limit the
      ability to detect gaps in the noise; 'dips' in the noise may be confused with the
      gap to be detected. For people with cochlear hearing loss, loudness recruitment
      may effectively magnify the fluctuations and this could partly account for the
      reduced ability to detect gaps in noise bands that is usually found for such
      people. Previously, we tested these ideas by processing the envelopes of noise
      bands to alter the amount of envelope fluctuation. We showed that instantaneous
      compression, implemented via processing of the Hilbert envelope, led to smaller
      (that is, better) gap detection thresholds for subjects with cochlear hearing
      loss. In the present experiment, we determined whether fast-acting compression of
      the type sometimes used in hearing aids could also lead to improved gap
      detection. A behind-the-ear (BTE) digital hearing aid was programmed to implement
      multi-band compression, either fast-acting or slow-acting (control condition). A
      reference condition using unaided listening was also used. Stimuli were delivered
      via an earphone placed over the hearing aid. Overall stimulus levels at the
      output of the hearing aid were similar across conditions. Thresholds for
      detecting gaps in noise bands centred at 4 kHz were measured as a function of
      noise bandwidth (10-500 Hz). To prevent the detection of spectral changes
      introduced by the gap, stimuli were presented in a broad-band background noise.
      Three normally hearing subjects and three subjects with bilateral cochlear
      hearing loss were tested. Gap thresholds varied non-monotonically with noise
      bandwidth, being maximal around 50 Hz. Gap thresholds were generally higher for
      the hearing-impaired than for the normally hearing subjects. For the latter, gap
      thresholds were similar for the three conditions. For the hearing-impaired
      subjects, gap thresholds were similar for the unaided condition and the condition
      using slow compression. However, fast compression led to smaller gap thresholds,
      especially for noise bandwidths up to 50 Hz. The results show that fast
      compression can improve the ability of hearing-impaired subjects to detect gaps
      in sounds with slowly fluctuating envelopes.

PMID- 11848179
TI  - Dietary sources of nutrient consumption in a rural Japanese population.
AB  - We determined the sources of nutrient intake of 59 men and 60 women in two rural
      towns in the Miyagi Prefecture, a northeastern part of Japan. Four 3-day food
      records were collected in four seasons within a year. The total dishes and
      recipes were classified into 197 items. Their percent contributions to the total
      population consumption of energy and 14 nutrients were calculated as the sum of
      the nutrient intake contributed by a given dish or recipe divided by the total
      nutrient intake from all the items. Rice was the largest contributor for energy
      (29.8%), protein (13.0%) and carbohydrates (45.3%). Miso soup, as a dish, was a
      leading contributor (7.1%) for fat. The largest contributor for sodium, calcium,
      carotene, vitamin C were miso soup (17.1%), milk (16.6%), spinach (23.6%), green
      tea (13.6%), respectively. The result suggests that the examination of nutrient
      sources based on dishes and recipes, rather than on food materials, may be useful
      in characterizing the dietary patterns of populations.

PMID- 11848180
TI  - Mortality rates from cancer or all causes and SOD activity level and Zn/Cu ratio
      in peripheral blood: population-based follow-up study.
AB  - A total of 507 residents (232 males and 275 females) of a rural area of Hokkaido,
      Japan, were enrolled in the present follow-up study as the follow-up cohort. We
      investigated the relationship between mortality rates from cancer or all causes
      and blood levels of SOD activity and Zn/Cu ratio, and serum levels of SOD
      activity and lipid peroxides (TBARS), by following up our subjects over the
      course of 18 years. The hazard ratios of lowest blood levels of SOD activity and
      Zn/Cu ratios to mortality rates from cancer were 1.36 (95% C.I.: 0.59-3.10) and
      1.97 (95% C.I.: 0.84-4.63), and those to mortality rates from all causes were
      1.31 (95%C.I: 0.76-2.27) and 1.99 (95%C.I.: 1.14-3.46), respectively, in
      comparison with subjects with highest values for these factors. Hazard ratios of
      lowest serum levels of SOD activity and TBARS to mortality rates from cancer were
      2.68 (95%C.I.: 1.05-6.82) and 0.71 (95%C.I.: 0.31-1.67), and those to mortality
      rates from all causes were 1.55 (95% C.I., 0.90-2.66) and 0.88 (95%C.I.: 0.51
      1.50), respectively. The results of this follow-up study indicate that high serum
      SOD activity is associated with protective effects against mortality from cancer,
      and that high blood Zn/Cu ratio is associated with low mortality from other
      causes. In contrast, serum TBARS levels do not appear to be a biomarker for the
      risk of death from cancer.

PMID- 11848181
TI  - The natural history model of hepatitis C virus infection and the economic
      evaluation of alpha interferon treatment.
AB  - Interferon (IFN) therapy is used for the treatment of hepatitis C virus (HCV)
      disease, but is so expensive that it creates controversy as to whether or not it
      is effective use of limited health care resources. In order to make this
      judgement possible, it must be necessary to build a comprehensive disease model
      of HCV infection from social perspective. A Markov chain model of the natural
      history of HCV infection in male patients was developed. Parameters on the
      clinical phase of the disease were adopted from published reports, but those of
      the non-clinical phase were estimated from the data on blood donation and
      mortality rates from the disease. Then, adding in the modeling of treatment
      outcome from IFN therapy and cost-benefit analysis, IFN therapy was economically
      evaluated. Using this model, it was shown that (1) IFN therapy for chronic
      hepatitis C (CHC) would be economically beneficial at least in the Japanese
      situation, (2) the complete response rate to therapy would be the most sensitive
      factor affecting outcome, and (3) the younger the person cured by IFN therapy,
      the greater the benefit seen. These results demonstrate that IFN therapy would be
      beneficial in the case of the CHC patients (male).

PMID- 11848183
TI  - Effects of low body mass index and smoking on all-cause mortality among middle
      aged and elderly Japanese.
AB  - To investigate effects of low body mass index (BMI) and smoking on all-cause
      mortality among middle-aged and elderly Japanese, we conducted a community-based
      prospective study. A mail survey was conducted in 1987-1990 in four towns,
      western Japan. A cohort of 7,301 Japanese men and 8,825 Japanese women was
      followed up from the date of the mail survey to 1995 in three of the towns and
      1998 in the fourth town. We investigated the effect of BMI and smoking on all
      cause mortality by using Cox's proportional hazards model. The relationship
      between BMI and all-cause mortality was a reverse J-shape with minimal mortality
      in 24 < or = BMI < 26 in men and a U-shape with minimal mortality in 22 < or =
      BMI < 24 in women, after adjusting for age and smoking. The lowest BMI category
      (BM < 20) had the highest all-cause mortality in men and also in women. Taking
      only never-smokers, the highest risk for all-cause mortality was observed in the
      lowest BMI category for men and for women. This does not seem to be explained by
      smoking and pre-existing diseases. More attention should be paid to persons with
      low BMI.

PMID- 11848182
TI  - Parental obesity, lifestyle factors and obesity in preschool children: results of
      the Toyama Birth Cohort study.
AB  - The aim of this study was to clarify the impact of parental obesity and lifestyle
      factors on obesity in preschool children. The subjects consisted of 8941 children
      aged 3 years, born in 1989. Anthropometric measurements and questionnaire surveys
      were conducted between 1992 and 1994. Subjects of body mass index (BMI; (weight
      (kg))/(height (m))2) more than the age- and sex-specific centiles linked to adult
      overweight were defined as obese subjects. Parental obesity was defined as BMI of
      25 kg/m2 or more. Logistic regression analysis was performed to clarify the
      strengths of parental and lifestyle factors on childhood obesity, adjusted for
      possible confounding factors. Odds ratios (ORs) of paternal and maternal obesity
      for childhood obesity were 1.70(1.43-2.02) and 2.56(2.07-3.17), respectively.
      There was a dose-response relationship between short sleeping hours and obesity.
      Compared to subjects taking 11 hours sleep or more, the adjusted OR was 1.20(0.97
      1.49) for those taking 10 to 11 hours sleep, 1.34(1.05-1.72) for those taking 9
      to 10 hours sleep, and 1.57(0.90-2.75) for those taking less than 9 hours sleep.
      Eating and exercising habits were not significantly associated with obesity.
      These results indicate that parental obesity and short sleeping hours are
      possible risk factors for obesity in preschool children.

PMID- 11848185
TI  - A supplementary comment on "Reliability and validity of a questionnaire for
      assessment of physical activity in epidemiological studies" published in Journal
      of Epidemiology, 1998.

PMID- 11848184
TI  - Reproducibility of a semi-quantitative food frequency questionnaire in Japanese
      female dietitians.
AB  - OBJECTIVE: To examine reproducibility of assessed intake of foods and nutrients
      according to a semi-quantitative food frequency questionnaire (SQFFQ) in Japanese
      female dietitians. SUBJECTS AND METHODS: An SQFFQ was self-administered to 106
      (21 male and 85 female) Japanese dietitians in Aichi prefecture in autumn 1996
      and the same questionnaire was repeated in autumn 1997. Reproducibility was
      evaluated in terms of consumption of 15 foods and energy and 30 macro- and micro
      nutrients based on the SQFFQ from 84 Japanese female dietitians. RESULTS: For
      intake of foods, Pearson's correlation coefficients (CCs) with log-transformation
      and energy adjustment (minimum-median-maximum) ranged from 0.35 (beverages)-0.61
      0.71 (dairy products). ANOVA intraclass correlation coefficients (ICCs) with log
      transformation and energy adjustment ranged from 0.49 (beverages)-0.74-0.82
      (dairy products). Spearman's rank CCs with energy adjustment ranged from 0.43
      (confectionery)-0.57-0.76 (dairy products). Weighted kappa statistics with energy
      adjustment ranged from 0.34 (confectionery)-0.49-0.71 (dairy products). For
      consumption of nutrients, Pearson's CCs with log-transformation and energy
      adjustment ranged from 0.23 (zinc)-0.55-0.74 (insoluble dietary fiber). ANOVA
      ICCs with log-transformation and energy adjustment ranged from 0.37 (zinc)-0.70
      0.84 (insoluble dietary fiber). Spearman's rank CCs with energy adjustment ranged
      from 0.25 (zinc)-0.56-0.74 (magnesium). Weighted kappa statistics with energy
      adjustment ranged from 0.25 (zinc)-0.50-0.68 (insoluble dietary fiber).
      CONCLUSIONS: Substantially high reproducibility of consumption of foods and
      nutrients was attained from an SOFFQ self-administered to Japanese female
      dietitians.

PMID- 11848186
TI  - Accuracy of the estimated prevalence of childhood obesity from height and weight
      values reported by parents: results of the Toyama Birth Cohort study.
AB  - The aim of the present study was to evaluate the validity of the estimated
      prevalence of childhood obesity from height and weight reported by parents. The
      subjects were 170 first-grade children (83 males and 87 females) and 206 fourth
      grade children (99 males and 107 females). A questionnaire including questions on
      height and weight was distributed to children and completed by parents.
      Anthropometric measurements were conducted in the standard way. Age- and sex
      specific cut-off points linked to adult overweight were employed to determine
      childhood obesity. The correlation and difference between reported and measured
      values were calculated separately for grade and gender. Correlation coefficients
      ranged from 0.90 to 0.96 for height, 0.95 to 0.99 for weight, and 0.86 to 0.97
      for body mass index (BMI). Sensitivity and specificity, the indices predicting
      the presence or absence of actual obesity from reported height and weight, ranged
      from 83.3 to 93.3% and 96.3 to 98.9%, respectively. The estimated prevalence of
      obesity (as calculated by reported data) minus actual prevalence (as calculated
      by measured data) ranged from -1.2 to 1.0%. These results indicate that height
      and weight reported by parents provides a reliable assessment of childhood
      obesity.

PMID- 11848187
TI  - A study of some parameters in stimulated saliva from adolescents with dental
      fluorosis.
AB  - In this study, parameters such as the flow rate, buffer capacity, sialic acid,
      protein and electrolyte concentrations, and amylase and peroxidase activities
      were analyzed in stimulated whole saliva from adolescents with dental fluorosis.
      From 135 adolescents (13 and 14 years-old) attending a primary and secondary
      school in the coastal city of Vitoria-Brazil, 72 were selected to participate in
      this study. The degree of fluorosis was graded using the TSIF, and was carried
      out by a calibrated and trained dentist. No variation in the flow rate, pH and
      buffer capacity, protein concentration or amylase activity was observed between
      the groups with dental fluorosis and the control group (fluorosis score 0). The
      peroxidase activity and sialic acid concentration showed some differences
      compared to the control. Sialic acid concentrations were reduced in the groups
      with dental fluorosis scores above 2. The concentration of Na was lower in
      adolescents with dental fluorosis, while Mg concentrations were higher in two
      fluorosis groups, Ca concentration was reduced in two groups with fluorosis. We
      conclude, that 13 and 14 year-old adolescents attending a school in the coastal
      city of Vitoria-Brazil showed no variations relative to some parameters and some
      variations in relation to others of the salivary parameters studied.

PMID- 11848189
TI  - Identification of 40-kDa outer membrane protein as an aggregation factor of
      Porphyromonas gingivalis to Streptococcus gordonii.
AB  - Porphyromonas gingivalis, an important pathogen in periodontitis, aggregates with
      other oral microorganisms such as Streptococcus gordonii. We previously succeeded
      in gene cloning the 40-kDa outer membrane protein (OMP) from P. gingivalis.
      Although recombinant (r) 40-kDa OMP itself did not show aggregation activity, the
      affinity-purified antibody against 40-kDa rOMP inhibited the aggregation activity
      of P. gingivalis cells toward S. gordonii which is one of the first oral bacteria
      to colonize on tooth surfaces and can be expected to support subsequent
      colonization of other bacteria. In this study, in order to clarify the
      pathological role of 40-kDa OMP, we used a cross-linking reagent to construct a
      polymeric form of r40-kDa OMP and examined its aggregation activity. The
      polymeric r40-kDa OMP significantly expressed aggregation activity with S.
      gordonii cells. Moreover, the antibody against r40-kDa OMP inhibited the
      aggregation activity of the polymeric r40-kDa OMP. These findings clearly
      demonstrate that 40-kDa OMP, as a multivalent form, is one of the important
      aggregation factors on the cell surface of P. gingivalis.

PMID- 11848188
TI  - Comparison of the cytotoxic effects and smear layer removing capacity of
      oxidative potential water, NaOCl and EDTA.
AB  - This study compared the smear layer removing capability and cytotoxicity of
      NaOCl, EDTA and Oxidative Potential Water (OPW). Fifteen extracted single-rooted
      human upper incisors were examined in three groups. The root canals were enlarged
      to the apical foramen with K files to size #60 and irrigated with: (a) NaOCl
      followed by OPW, (b) OPW during and after instrumentation and (c) NaOCl followed
      by EDTA and NaOCl. The effect of these irrigants on the smear layer was evaluated
      using a scanning electron microscope. In vitro cytotoxicity of these irrigants
      was examined by MTT colorimetric assay. We found that the combination of NaOCl
      and OPW as well as the application of OPW alone, failed to remove the smear layer
      from the apical third, whereas the EDTA and NaOCl combination achieved complete
      removal. OPW, when used during and after instrumentation, removed the smear layer
      in the middle third more effectively than NaOCl followed by OPW. EDTA exerted
      more cytotoxic effects at all concentrations tested when compared with OPW and
      NaOCl. IN CONCLUSION: (a) OPW was less cytotoxic than other irrigants but did not
      effectively remove the smear layer, (b) treatment with EDTA followed by NaOCl
      efficiently removed of the smear layer, but their cytotoxicity should be
      considered during endodontic therapy.

PMID- 11848190
TI  - The effect of various root canal sealers on India ink and different
      concentrations of methylene blue solutions.
AB  - In this study, the effect of different root canal sealers on 1%, and 2% methylene
      blue (MB) solutions and India ink were analyzed using spectrophotometry. One
      hundred and twelve specimens were used in this study. One hundred and five
      plastic tubes were filled with Sealapex, Endomethasone, Sultan, AH Plus or Ketac
      Endo. Twenty-one plastic tubes were used for each group. Seven plastic tubes were
      not filled, serving as controls. Seven specimens were taken from each group
      randomly and immersed in 0.8 ml 1% MB, 2% MB or black India ink. The optical
      density of the solutions after 0, 24, 48 and 72 hours of immersion was measured
      in a spectrophotometer at 416 nm. The optical density (OD) of the solutions was
      stable for the control group. The OD values for the 1% MB solutions were
      increased in the Sealapex and Sultan groups. The OD values for the 2% MB
      solutions were also increased for Sealapex and AH Plus. OD values were decreased
      for all India ink groups. The change in OD values relating to each time interval
      was statistically analyzed for each test material using two-way ANOVA. In the dye
      leakage studies, India ink, when compared to MB solutions, was a more reliable
      tracer as no dissolution of the root canal sealers occurred in contact with India
      ink.

PMID- 11848191
TI  - Does temporary splinting before non-surgical therapy eliminate scaling and root
      planing-induced trauma to the mobile teeth?
AB  - The objective of this study was to determine whether temporary splinting of
      periodontitis-affected mobile teeth, prior to non-surgical mechanical therapy,
      affects treatment outcome by eliminating scaling and root planing-induced trauma
      to the teeth. Mandibular anterior teeth of 29 patients (15 females; 14 males; age
      range 30 to 48 years) with adult periodontitis were evaluated. Clinical
      measurements were performed at 4 sites per tooth including mesial, distal, buccal
      and lingual aspects at baseline, 3 and 6 months after treatment. The following
      clinical parameters were analyzed: plaque index (PI), gingival index (GI),
      bleeding on probing (BOP), pocket depth (PD), probing attachment level (PAL),
      gingival margin level (GML) and tooth mobility (TM). Patients were randomly
      divided into 3 groups: i) group 1 (n = 8) received scaling and root planing (SRP)
      only, ii) group 2 (n = 10) received scaling and root planing before splinting and
      iii) group 3 (n = 11) received scaling and root planing after splinting.
      Statistical analysis revealed that there were no significant differences among
      the groups for either bleeding on probing or probing attachment level values at
      any of the time intervals. At the end of the study, the greatest decrease in
      pocket depth was noted in group 2 (1.24+/-0.10 mm) which was thought to be the
      result of gingival recession (0.73+/-0.07 mm). Group 1 was the only group that
      showed reduction in tooth mobility at 3 months compared to baseline (1.67+/-0.55
      PTV units). Group 3 displayed the least reduction in tooth mobility during the
      entire study period (0.26+/-0.44 PTV units). In conclusion, splinting of mobile
      teeth before SRP, and thereby elimination of potential SRP-induced trauma to the
      mobile teeth, did not show any adjunctive effect on healing when compared to
      splinting after SRP. Thorough debridement of root surfaces, even performed in the
      presence of increased mobility, resulted in improvements in clinical parameters,
      i.e. mechanical manipulation of mobile teeth during periodontal treatment did not
      affect clinical outcome negatively.

PMID- 11848192
TI  - The effects of folic acid application on IL-1beta levels of human gingival
      fibroblasts stimulated by phenytoin and TNFalpha in vitro: a preliminary study.
AB  - Folic acid (FA), that is required for the integrity of gingival tissues, was
      found to decrease in patients using phenytoin (PHT). Interleukin-1 beta (IL
      1beta) was reported to enhance the extracellular matrix synthesis in fibroblasts.
      The purpose of this study was to assess the role of FA supplementation on PHT
      induced overgrowth by investigating its effect on IL-1beta production of human
      gingival fibroblasts induced by tumor necrosis factor alfa (TNFalpha) in cell
      culture. PHT (20 microg/ml), FA (20 or 40 ng/ml) + PHT, PHT + TNF (10 ng/ml), FA
      (20 or 40 ng/ml) + PHT + TNF, or only culture medium (control) was added to 24
      well plates containing fibroblasts. After an incubation period of 72 h, culture
      medium and cells were harvested separately. Then, IL-1beta levels in cell lysate
      were measured using enzyme-linked immunosorbent assay. The cellular IL-1beta
      level in the PHT group was 1 pg/ml. In PHT + 20 or 40 ng/ml FA-added cultures,
      the results obtained respectively were 0.8 and 0.7 pg/ml, whereas the control
      group value was 0.7 pg/ml. IL-1beta level was 4 pg/ml in the cultures that PHT
      and TNFalpha were applied simultaneously (P < 0.05). When PHT and either 20 or 40
      ng/ml FA were simultaneously added into TNFalpha-induced cultures, the IL-1beta
      levels were 1.8 and 1.3 pg/ml, respectively. IL-1beta level in gingival tissues
      might play a role in PHT-induced overgrowth by increasing in the gingival
      tissues, and FA application might play a role in decreasing gingival tissues.
      However, further studies are needed for a more complete understanding of PHT
      induced gingival overgrowth at the cellular level.

PMID- 11848194
TI  - Light and scanning electron microscopic studies of the angioarchitecture of
      intrinsic muscle fibers of the anterior rat tongue.
AB  - Histological and scanning electron microscopy (SEM) characteristics of the
      microvasculature of muscle fibers in the anterior third of the adult rat tongue
      are described. For light microscopy, the specimens were embedded in paraffin and
      frontal sections were stained with Picro-Sirius. Thick sections were obtained
      from Spurr embedded samples and stained with toluidine blue solution. For SEM,
      specimens were obtained by the corrosion cast method and fractured specimens in
      dimethyl sulfoxide were observed with high-resolution SEM (HRSEM). The blood
      vessels, enveloped with a thin layer of connective tissue, had fibers running
      parallel to the muscular fibers. Capillary arterioles were noted following the
      endomysium, but their lateral branches often ran at right angles to the fibers.
      The capillary beds were clearly revealed in transverse sections where the
      individual capillaries appeared ring-like or elliptical in shape. The nuclei of
      endothelial cell cores could be seen on the vessel surfaces. Collagen fibers type
      I and III were noted in the connective tissue and in the fibrous layer of
      vessels.

PMID- 11848193
TI  - Comparative study of calcium-channel blockers on cell proliferation, DNA and
      collagen syntheses, and EGF receptors of cultured gingival fibroblasts derived
      from human nifedipine, nicardipine and nisoldipine responders.
AB  - Our previous study indicated that fibroblasts derived from patients reactive to
      nifedipine might be susceptible to the other calcium-channel blockers
      (nicardipine, verapamil and diltiazem) in terms of cell proliferation, DNA
      synthesis, and collagen synthesis. Thus, the present investigation was designed
      to clarify the cross-reactivity among dihydropyridine calcium-channel blockers
      (nifedipine, nicardipine, and nisoldipine). Human gingival fibroblasts derived
      from seven, two, and one patients who developed gingival overgrowth as a result
      of nifedipine, nicardipine, and nisoldipine medications, respectively, were
      examined in terms of the effect of calcium-channel blockers (nifedipine,
      diltiazem, verapamil, and nicardipine) on cell proliferation, DNA synthesis,
      collagen synthesis, and the number of epidermal growth factor (EGF) receptors.
      Phenytoin was used as a positive control. With most of the calcium-channel
      blockers and phenytoin, fibroblasts from patients reactive to nifedipine and
      nicardipine medications gave a better cell proliferation rate, DNA synthesis, and
      an increased number of EGF receptors, compared to non-drug-treated control.
      However, this was not the case for calcium-channel blockers tested in fibroblasts
      from patients reactive to nisoldipine medication.

PMID- 11848196
TI  - An adenomatoid odontogenic tumor with unusual clinical features.
AB  - Adenomatoid odontogenic tumors are uncommon odontogenic lesions characterized by
      duct-like structures that form from the epithelial component of the lesion. Most
      of these masses develop in the second or third decade of life, and there is a
      strong female bias in occurrence. Typically, these lesions arise in the lateral
      incisor/canine region of the maxilla, where they produce a swelling. Only in very
      rare cases is the lesion found distal to the premolar area. Nearly all of these
      growths are associated with an embedded anterior maxillary tooth (usually a
      canine), and most resemble a 1-3 cm diameter dentigerous cyst. Radiopacity is
      reported in two-thirds of cases. This article describes the case of a 9-year-old
      Caucasian male who presented with a painless swelling in the left premolar-molar
      region of his maxilla. This case is of particular interest because the features
      (patient age, gender, lesion location, size, and radiographic findings) were not
      typical of adenomatoid odontogenic tumor.

PMID- 11848195
TI  - A comparative analysis of the structure of the dentinoenamel junction in mammals.
AB  - Studies of the gross morphology and microstructure of teeth have provided a great
      deal of information about the function and evolution of mammals. Among the
      structural features studied, the dentinoenamel junction has received relatively
      little attention. In the present work, we used ground sections to perform a
      comparative analysis of the structure of the dentinoenamel junction (DEJ) among
      diverse mammalian species. Among the species studied, only two (human and
      Miguelsoria parayirunhor) presented a scalloped DEJ. In the other 14 species
      analyzed, the DEJ surface was formed by tiny spikes and depressions,
      corresponding to the impression of enamel prisms. Our results show that the
      topography of the DEJ in the analyzed taxa apparently does not relate to dietary,
      functional or structural features.

PMID- 11848197
TI  - Primary intraosseous carcinoma associated with impacted third molar of the
      mandible: review of the literature and report of a new case.
AB  - This study investigated the clincopathologic features of primary intraosseous
      carcinoma (PIOC) related to the third molar of the mandible. Six cases (5 from
      the literature and 1 new case; mean patient age 73 years) of PIOC associated with
      completely impacted lower third molar were analyzed. For comparison, 8 cases of
      PIOC presenting after extraction of the lower third molar were also evaluated,
      with a significantly lower mean patient age of 56 years. Most lesions were
      deceptively similar to those related to the lateral type of dentigerous cyst, and
      half of the impacted cases revealed an asymptomatic fracture of the mandible. In
      all patients except for the present case, metastasis had not been recorded.
      Surprisingly, no patients are known to have died of PIOC. In our experience the
      prognosis of PIOC associated with a completely impacted third molar is much
      better than commonly believed, although the number of cases involved is too small
      to make a general conclusion. However, delay in establishing the correct
      diagnosis followed by extraction without awareness of the carcinoma is know to
      adversely affect the prognosis.

PMID- 11848198
TI  - Osteochondroma of the mandibular condyle: a case report and review of the
      literature.
AB  - Osteochondroma is rarely found in the oral and maxillofacial regions. A rare case
      of osteochondroma affecting the mandibular condyle of a 46-year-old Japanese
      woman is reported. Clinical examination revealed facial asymmetry, malocclusion,
      and a palpable hard mass in the right temporomandibular joint (TMJ).
      Radiologically, the lesion was visualized as a radiopaque mass in the same
      region, but no destructive features were evident. Three-dimensional computed
      tomography was employed for estimating the stereographic extension of the lesion,
      which seemed to develop from the anterior portion of the condylar neck, and
      extend to the condylar head. The patient underwent tumor excision and
      condyloplasty under a clinical diagnosis of benign TMJ tumor. The
      histopathological diagnosis was osteochondroma of the mandibular condyle, and the
      lesion consisted of proliferative bony and hyalinized cartilage-like tissues.
      Moreover, a cartilage cap, a characteristic feature of osteochondroma, was also
      observed. Thirty-eight cases of osteochondroma of the mandibular condyle
      described in the English literature, including the present case, were reviewed.
      The mean patient age was 39.7 years with a peak in the fourth decade, which was
      older than patients with tumors in the axial skeleton. There was no sexual
      predominance for tumors in either the mandibular condyle or axial skeleton. The
      histopathogenesis of this tumor developing in the mandibular condyle was also
      discussed.

PMID- 11848199
TI  - Method of evaluation of the bitterness of clarithromycin dry syrup.
AB  - The degree of bitterness of clarithromycin (CAM) dry syrup was evaluated using
      several methods. Using the inversion method, shaking method, and paddle method, a
      reasonable correlation between the bitter taste and the amount dissolved was not
      observed. A mini-column with inner diameter of 0.76 cm and height of 5 cm packed
      with CAM dry syrup was used for the release test. The release rate of CAM in test
      solution, which passed through the mini-column, was then measured to evaluate
      bitterness. The release rate of CAM in the release test using the mini-column
      correlated well with the results of a sensory test for the bitterness of CAM dry
      syrup. The dissolution rate constant, defined as the percentage of CAM dissolved
      from the unit void surface multiplied by the void volume, was inversely
      proportional to the linear velocity of the test solution. The critical factors
      affecting evaluation of bitterness were the void volume of the column and linear
      velocity of the test solution. The optimum linear velocity and void volume were
      0.048-0.021 cm/min and 0.27-0.12 cm3, respectively. In addition, the threshold of
      bitterness of CAM dry syrup was defined as the concentration at which half of the
      volunteers recognized bitterness in the sensory test. This threshold was found to
      be 135 microg/ml using the mini-column.

PMID- 11848200
TI  - Transformation of metastable forms of acetaminophen studied by thermal Fourier
      transform infrared (FT-IR) microspectroscopy.
AB  - A novel Fourier transform infrared (FT-IR) microspectroscopy equipped with a
      micro hot stage (thermal FT-IR microscopic system) was used to quickly study the
      phase transformation of acetaminophen polymorphs by a one-step process.
      Acetaminophen was sealed in KBr disc on the first and second heating processes
      under this system. The results indicate that the contour IR profile of form I
      acetaminophen in the first heating process changed dramatically only near 165
      degrees C, but in the re-heating process exhibited a considerable alteration in
      peak intensity, band width and position near the temperatures at 85, 118 and 153
      degrees C. A glassy form of acetaminophen was obtained after rapidly cooling the
      melted acetaminophen from 200 to 25 degrees C. The glassy acetaminophen was
      recrystallized at 85 degrees C to transform to the form III of acetaminophen in
      the reheating process, and then transformed to its form II near 118 degrees C.
      The thermal FT-IR microscopic system is a simple, quick and timesaving tool for
      investigation of the thermo-dependent molecular structure of acetaminophen
      polymorphs in the processes of recrystallization and polymorphic transition.

PMID- 11848201
TI  - New pavine N-oxide alkaloids from the stem bark of Cryptocarya chinensis Hemsl.
AB  - Three new pavine N-oxide alkaloids, (-)-isocaryachine-N-oxide B, (+)-caryachine-N
      oxide, (-)-caryachine-N-oxide, and a new isoquinoline alkaloid, 6,7
      methylenedioxy-N-methylisoquinoline together with 11 known alkaloids were
      isolated and characterized from the stem bark of Cryptocarya chinensis. The
      structures of the isolated compounds were determined by spectral methods. The
      stereochemistry of pavine-N-oxide alkaloids is also discussed.

PMID- 11848202
TI  - Biotransformation of phorbol by human intestinal bacteria.
AB  - Anaerobic incubation of phorbol (1) from Croton tiglium with human intestinal
      bacteria afforded five metabolites: isophorbol (2), deoxyphorbol (3),
      4beta,9alpha,20-trihydroxy-13,15-seco-1,6,15-tigliatriene-3,13-dione (4),
      4beta,9alpha,20-trihydroxy-15,16,17-trinor-1,6-tigliadiene-3,13-dione (5) and
      4beta,9a,20-trihydroxy-14(13-->12)-abeo-12alphaH-1,6-tigliadiene-3,13-dione (6).
      All these metabolites (2-6) were identified and characterized by spectroscopic
      means, including two-dimensional (2D)-NMR. Nine defined strains from the human
      intestine showed an ability to transform 1 to these metabolites.

PMID- 11848203
TI  - Antioxidant activity of novel indole derivatives and protection of the myocardial
      damage in rabbits.
AB  - Novel indole derivatives containing a triazole moiety (1a-d, 2a-c) were
      synthesized as lead compounds with interesting pharmacological profiles. Their
      antioxidant activity was investigated on in vitro non-enzymatic rat hepatic
      microsomal lipid peroxidation. All compounds showed significant effect in the
      above assay. The effect depended mainly on the attachment position of the
      triazole moiety on the indole nucleus. The most potent antioxidant derivatives
      la, 1c and 1d were tested for their protective ability against the oxidative
      damage of the myocardium after ischemia-reperfusion, in male rabbits which were
      subjected to 30 min regional ischemia followed by reperfusion. The tested
      antioxidant compounds 1a, 1c and 1d were continuously infused for 30 min starting
      at 10th min of ischemia and lasted at 10th min of reperfusion. The concentration
      of malondialdehyde (MDA, a marker of lipid peroxidation) and hemodynamic
      parameters (blood pressure and heart rate) were measured in the baseline, at 20th
      min of the sustained ischemia, 1st and 20th min of reperfusion. It was found that
      the examined compounds la, 1c and 1d reduced significantly the level of MDA in
      rabbits under ischemia-reperfusion and proved to be promising substances for
      further evaluation of anti-ischemic properties.

PMID- 11848204
TI  - Assessment of acyl groups and reaction conditions in the competition between
      perhydrolysis and hydrolysis of acyl resorufins for developing an indicator
      reaction for fluorometric analysis of hydrogen peroxide.
AB  - Perhydrolysis of acetyl resorufin (AR) was reported previously to work as a
      fluorometric indicator reaction for glucose determination using only glucose
      oxidase. However, hydrolysis of AR in blank solution rendered the working
      concentration range of this method less than two orders of magnitude. To exclude
      or at least significantly reduce this interference, acyl groups and reaction
      conditions in the competition between perhydrolysis and hydrolysis of various
      acyl resorufins were assessed. Fluorometric evaluation of reactions in the
      presence or absence of H202 in phosphate buffer (pH 7.5, 100 mm)-CH3CN at 25
      degrees C demonstrated that in tert-butylacetyl, isobutyryl, cyclohexanecarbonyl
      and pivaloyl resorufins (TBAR, IBR, CHR and PVR, respectively) among 10 acyl
      resorufins examined here, the competitive situation was shifted in a much more
      favorable way to perhydrolysis than in AR, although fluorometric responses due to
      their H2O2-dependent deacylation were suppressed in comparison with AR.
      Examination of the effects of pH, components and concentrations of buffers as
      well as reaction temperature established reaction conditions that not only
      allowed perhydrolysis of each of these four compounds to prevail over hydrolysis
      more effectively, but also improved the H2O2-based fluorometric responses. Thus,
      perhydrolysis of TBAR, IBR, CHR and PVR in phosphate buffer (pH 8.0, 20 mM)-CH3CN
      at 25 degrees C worked effectively as fluorometric indicator reactions for H2O2
      analysis, affording a calibration curve over a concentration range of three
      orders of magnitude. Taking sensitivity, reproducibility and the response for
      blank solution into consideration, PVR seemed to be the best choice as a
      fluorochromogen for H2O2 determination under these conditions. For H2O2 analysis
      at lower pH, perhydrolysis of IBR in phosphate buffer (pH 7.5, 20 mm)-CH3CN was
      shown to effectively function as an indicator reaction. Applicability of the
      fluorometric methods with PVR and IBR to blood glucose determination was also
      discussed, comparing with Trinder's method with phenol, 4-aminoantipyrine and
      peroxidase (POD).

PMID- 11848205
TI  - Purification and characterization of ginsenoside-alpha-L-rhamnosidase.
AB  - In this paper the ginsenoside-alpha-(1-->2)-L-rhamnosidase from microorganisms
      was purified and characterized. The enzyme hydrolyzed the 6-C, alpha-(1-->2)-L
      rhamnoside of 20(S) and 20(R)-ginsenoside Rg2 to produce the 20(S) and 20(R)
      ginsenoside Rh1, but hardly hydrolyzed the alpha-rhamnoside of pNPR. The enzyme
      molecular weight was about 53 kDa. The optimum temperature of enzyme reaction was
      40 degrees C, and the optimum pH was 5.

PMID- 11848206
TI  - Generation of superoxide anions during the reaction of guanidino compounds with
      methylglyoxal.
AB  - Uremic toxins are accumulated in the blood of patients with chronic renal failure
      (CRF), although alteration of the toxicity by the interaction of various uremic
      retention products has not been precisely clarified. In this study, we found that
      cytochrome c added to incubation mixtures containing guanidino compounds and
      methylglyoxal in phosphate buffer solution (pH 7.4) resulted in reduction of
      cytochrome c. Superoxide anions were generated from incubation mixtures of each
      guanidino compound with methylglyoxal, because the reduction was inhibited by the
      addition of superoxide dismutase. The incubation mixture containing each
      guanidino compound and methylglyoxal had different rates of generation of the
      superoxide anion from other mixtures. A relatively higher superoxide anion
      formation rate was observed in the incubation mixture containing Arg and
      methylglyoxal (7.9 +/- 0.5nmol x m(-1) x min(-1)), or in the incubation mixture
      containing methylguanidine and methylglyoxal (6.3 +/- 0.6 nmol x ml(-1) min(-1)).
      These findings suggest that interactions of various uremic retention products
      which accumulate in the blood of uremic patients may generate reactive oxygen
      species and may be involved in the oxidative stress observed in CRF patients. The
      addition of aminoguanidine, which is known to inhibit the formation of advanced
      glycation end products, to a mixture of guanidino compounds and methylglyoxal
      inhibited reactions between guanidino compounds and methylglyoxal.

PMID- 11848207
TI  - Five new nortropane alkaloids and six new amino acids from the fruit of Morus
      alba LINNE growing in Turkey.
AB  - Investigation of the constituents of the fruits of Morus alba LINNE (Moraceae)
      afforded five new nortropane alkaloids (1-5) along with nor-psi-tropine (6) and
      six new amino acids, morusimic acids A-F (7-12). The structures of the new
      compounds were determined to be 2alpha,3beta-dihydroxynortropane (1), 2beta,3beta
      dihydroxynortropane (2), 2alpha,3beta,6exo-trihydroxynortropane (3),
      2alpha,3beta,4alpha-rihydroxynortropane (4), 3beta,6exo-dihydroxynortropane (5),
      (3R)-3-hydroxy-12-[(1S,4S)-4-[(1S)-1-hydroxyethyl]-pyrrolidin-1-yll-dodecanoic
      acid-3-O-beta-D-glucopyranoside (7), (3R)-3-hydroxy-12-[(1S,4S)-4-[(1S)-1
      hydroxyethyl]-pyrrolidin-1-yll-dodecanoic acid (8), (3R)-3-hydroxy-12-1(1R,4R,5S)
      4-hydroxy-5-methyl-piperidin-1-yll-dodecanoic acid-3-O-beta-D-glucopyranoside
      (9), (3R)-3-hydroxy-12-[(1R,4R,5S)-4-hydroxy-5-methyl-piperidin-1-yll-dodecanoic
      acid (10), (3R)-3-hydroxy-12-[(1R,4R,5S)-4-hydroxy-5-hydroxymethyl-piperidin-1
      yl]-dodecanoic acid-3-O-beta-D-glucopyranoside (11), and (3R)-3-hydroxy-12
      [(1R,4S,5S)-4-hydroxy-5-methyl-piperidin-1-yl]-dodecanoic acid (12) on the basis
      of spectral and chemical data.

PMID- 11848208
TI  - Studies of rapidly disintegrating tablets in the oral cavity using co-ground
      mixtures of mannitol with crospovidone.
AB  - We attempted the development of rapid oral disintegration tablets by direct
      compression using co-ground mixture of D-mannitol and crospovidone. The co-ground
      mixture was prepared with a vibration rod mill. The tablets were formed by
      compression using a single punch-tableting machine after addition of the co
      ground mixture to non-ground D-mannitol, crospovidone and magnesium stearate.
      Regarding the properties of tablets, hardness and the time of disintegration were
      measured. The particle diameter and specific surface area of the co-ground
      mixture were measured. The tablets manufactured from a physical mixture of 30%
      (w/w) co-ground mixture of D-mannitol and crospovidone (mixed ratio 9 :1) with
      65.5% (w/w) of non-ground mannitol, 4% (w/w) of crospovidone, and 0.5% (w/w) of
      magnesium stearate had good properties for rapidly disintegrating tablets in the
      oral cavity. They showed the hardness of 4.9 kg and disintegration time of 33 s.
      We found that adding co-ground mixture of D-mannitol and crospovidone is useful
      in enhancing hardness of the tablets that could not be achieved by addition of
      their individually ground mixture. The improvement in the hardness of the tablets
      was also observed when other saccharides and disintegrants were used. This method
      was proved to be applicable in the manufacture of tables of ascorbic acid, a
      water-soluble drug and nifedipine, a slightly water soluble drug; and the
      dissolution rate of nifedipine from the tablets in water was remarkably improved.
      The particle sizes of D-mannitol in the co-ground mixture were smaller than that
      of the individually ground mixture, resulting in a larger specific surface area
      of the co-ground mixture than that of the individually ground mixture. Therefore,
      it was presumed that crospovidone acted as a grinding assistant for D-mannitol in
      the co-grinding process, enhancing the hardness of tablets by increasing the
      contact area among powder particles.

PMID- 11848209
TI  - New sesquiterpenes from Euonymus europaeus (Celastraceae).
AB  - A new sesquiterpene evoninate alkaloid (1), and two sesquiterpenes (2, 3) with a
      dihydro-beta-agarofuran skeleton, along with three known sesquiterpenes (4-6),
      were isolated from the seeds of Euonymus europaeus. Their structures were
      elucidated by high resolution mass analysis, and one- and two-dimensional (1D and
      2D) NMR spectroscopy, including homonuclear and heteronuclear correlation
      [correlation spectroscopy (COSY), rotating frame Overhauser enhancement
      spectroscopy (ROESY), heteronuclear single quantum coherence (HSQC), and
      heteronuclear multiple bond correlation (HMBC)] experiments.

PMID- 11848210
TI  - The role of Fe3+ on Fe2+-dependent lipid peroxidation in phospholipid liposomes.
AB  - Fe2+-dependent lipid peroxidation in phosphatidylcholine (PC) liposomes, assessed
      by thiobarbituric acid-reactive substances (TBARS) production, was stimulated in
      the presence of Fe3+ in a concentration-dependent manner. The rates of nitroblue
      tetrazolium (NBT) reduction and Fe2+ oxidation (Fe2+ disappearance and Fe3+
      formation) were also enhanced by the addition of Fe3+ to the reaction mixture,
      and there is a good linear relationship between these parameters. These results
      suggest that the facilitation of reactive oxygen species (ROS) production via
      Fe2+ oxidation is closely related to the onset of the stimulatory effect of Fe3+
      on Fe2+-dependent lipid peroxidation. On the other hand, results using the
      liposomes containing various concentrations of endogenous lipid hydroperoxides
      (LOOH) indicated that endogenous LOOH is not directly involved in the onset of
      the Fe3+ stimulatory effect on Fe2+-dependent TBARS production and ROS
      production. This hypothesis was further confirmed by the evidence that Fe2+
      dependent ROS production and Fe2+ oxidation of dipalmitoylphosphatidylcholine
      liposomes were also stimulated by the addition of Fe3+. The results with several
      antioxidants and radical scavengers suggested that ROS related to Fe2+-dependent
      lipid peroxidation and its stimulation by Fe3+ are ferrous-oxygen complexes
      rather than superoxide anion, hydrogen peroxide and hydroxyl radicals. Based on
      these results, we proposed a possible mechanism for the onset of the Fe3+
      stimulation in Fe2+-dependent lipid peroxidation.

PMID- 11848211
TI  - Bioactive constituents of Chinese natural medicines. VII. Inhibitors of
      degranulation in RBL-2H3 cells and absolute stereostructures of three new
      diarylheptanoid glycosides from the bark of Myrica rubra.
AB  - Three new diarylheptanoid glycosides, named (+)-S-myricanol 5-0-beta-D
      glucopyranoside, myricanene A 5-O-alpha-L-arabinofuranosyl(1-->6)-beta-D
      glucopyranoside, and myricanene B 5-0-alpha-L-arabinofuranosyl(1-->6)-beta-D
      glucopyranoside, were isolated from the bark of Chinese Myrica rubra, together
      with twenty known compounds. The absolute stereostructures of the new
      diarylheptanoid glycosides were elucidated on the basis of chemical and
      physicochemical evidence, including the application of the modified Mosher's
      method. The inhibitory effects of isolated constituents on the release of beta
      hexosaminidase from RBL-2H3 cells were examined, and several diarylheptanoids,
      myricanol, (+)-S-myricanol, myricanone, and myricanenes A and B, and a flavonol,
      myricetin, were found to show the inhibitory activity.

PMID- 11848212
TI  - Visualization of complexes of Hoechst 33258 and DNA duplexes in solution by
      atomic force microscopy.
AB  - Tertiary structure changes in DNA duplexes, induced by Hoechst 33258 binding,
      have been examined by the use of atomic force microscopy. Besides minor groove
      binding, which is an established mode of binding for this drug, Hoechst 33258 has
      now been found to show another binding mode, which causes an unwinding of the
      duplex. When the drug concentration is as high as 0.5 microg/ml, the Hoechst
      33258 molecule seems to function as a clamp for two DNA chains and forms a
      condensate. The condensate was found to have a toroidal shape. By surveying more
      than 100 microscopic images of such condensates formed in I microg/ml drug
      solution, a mechanism of toroidal condensate formation has been proposed.

PMID- 11848213
TI  - Release from or through a wax matrix system. II. Basic properties of release from
      or through the wax matrix layer.
AB  - In order to examine basic properties of release from and through wax matrix
      layer, reservoir device matrix tablet was prepared from a physical mixture of
      hydrogenated caster oil and drug that was the same one in the reservoir. Release
      process could be divided into two stages. The first stage was the formation
      process of water channel by dissolving the drug in the wax matrix layer, and
      dissolved drug was released from the matrix layer following the square-root-of
      time law equation. Hence, the drug penetration coefficient and tortuosity in the
      matrix layer were estimated. The second stage was the zero order release process
      of drug in the reservoir through the wax matrix layer. The release rate constant
      was calculated from the slope of line. Hence, the drug permeability coefficient
      and tortuosity were estimated. Fundamentally, tortuosity can not be expressed by
      some meaningful factors, and is obtained as an experimental result. By preparing
      wax matrix system from a physical mixture other than melted granule method, it
      was suggested that the matrix structure was uniform three-dimensionally. As a
      result, tortuosity could be expressed by a function of porosity, because
      unrecognized factors such as the surface coverage and thickness of melted wax on
      the soluble component should not be involved.

PMID- 11848214
TI  - Reaction of 1-alkylthioisoquinolinium salts with active methylene compounds.
AB  - 2-Alkyl-1-alkylthioisoquinolinium salts were readily prepared from 2-alkyl-1(2H)
      isoquinolones via 2-alkyl1(2H)-thioisoquinolones in two steps. Under mild
      conditions, the reaction of 2-alkyl-1-alkylthioisoquinolinium salts with active
      methylene compounds in the presence of sodium hydride afforded 2-alkyl-1
      (substituted methylene)iso-quinolines in good yields. Pyrrolo[2,1-a]isoquinolines
      were synthesized by the cyclization of 2-benzyl-1-(substituted
      methylene)isoquinolines using acetic anhydride.

PMID- 11848216
TI  - Synthesis of 2,3-disubstituted indole using palladium(II)-catalyzed cyclization
      with alkenylation reaction.
AB  - The reaction of ethyl 2-ethynylphenylcarbamate derivative with alkenes in the
      presence of a palladium(II) catalyst, copper dichloride and tetrabutylammonium
      fluoride (TBAF) produced 2-substituted 3-ethenylindoles during refluxing. The
      intramolecular cyclization reaction of ethyl 2-ethynylphenylcarbamates, which
      have an ethenyl part in the ethynyl group, was also used to produce carbazole
      derivatives.

PMID- 11848215
TI  - Photochemical behavior of sitafloxacin, fluoroquinolone antibiotic, in an aqueous
      solution.
AB  - Sitafloxacin (STFX) hydrate, an antimicrobial agent, is photo-labile in aqueous
      solutions. The photodegradation rates (k) in neutral solutions were higher than
      those observed in acidic and alkaline solutions and maximum at the maximum
      absorption wavelength of STFX. The structures of photodegradation products were
      elucidated as 7-[7-amino-5-azaspiro[2.4]heptan-5-yl]-6-fluoro-1,4-dihydro-4-oxo-3
      quinolinecarboxylic acid and 1-(1-amino-2-[16-fluoro-1-(2-fluoro-1-cyclopropyl)
      1,4-dihydro-4-oxo-3-quinolin-7-yl]-amino]ethyl)cyclopropanecarbaldehyde. This
      implies that dechlorination is the key step in the photodegradation of STFX. The
      effect of halide ions on the photodegradation of STFX was estimated by observing
      the increments in the photostability of STFX with the addition of chloride ions.
      In contrast, in the presence of bromide ions, instead of increased photostability
      of the STFX rate, a new photodegradation product in the presence of bromide ion
      was observed. The structure of this new photodegradation product was an 8-bromo
      form of STFX, which was substituted for chlorine at the 8-position, so the
      dissociation of C-Cl bond at the 8-position of STFX was the rate-limiting step in
      the initial process of the photodegradation. STFX generated .C (carbon centered
      radical) and .OH (hydroxyl radical) in the process of photodegradation in a pH
      4.0 buffer. On the contrary, STFX did not generate C in the presence of chloride
      ion in a pH 4.0 buffer. The .C was generated and then degraded into the above
      degradation products by photoirradiation in the absence of chloride ion, but the
      .C immediately reacted with chloride when it was present. As a result, the C-Cl
      bond was recovered leading to a possible increase in the apparent photostability.

PMID- 11848217
TI  - Design and synthesis of sulfur based inhibitors of matrix metalloproteinase-1.
AB  - Fibroblast collagenase (MMP-1), a member of the matrix metalloproteinases family,
      is believed to be a pathogenesis of arthritis, by cleaving triple-helical type II
      collagen in cartilage. From the similarity of the active site zinc binding mode
      with hydroxamate, we designed and synthesized alpha-mercaptocarbonyl possessing
      compounds (3-5), which incorporated various peptide sequences as enzyme
      recognition sites. The P4-P1 peptide incorporating compound (3) exhibited as
      potent inhibition as the hydroxamate (1) and the carboxylate (2) type inhibitors,
      with an IC50 of 10(-6) M order against MMP-1. But the inhibitor (3) related
      compounds (6-8) displayed decreased or no inhibitory potencies. These results
      suggest that the existence of both the carbonyl and thiol groups might be
      critical for the inhibition, and the distance between the two functional groups
      is important for inhibitory potency. For Pn' peptide incorporating compounds (4a
      k), except for 4h and 4k, all compounds showed IC50 values under sub-nanomolar.
      Among them, for potent inhibition, Leu was better than Phe and Val as the P1'
      amino acid, and the P2' position amino acid was necessary, and preferentially
      Phe. Insertion of the Pn peptide into 4d or 4k, giving compounds 5a-c, did not
      increase the activities of 4d and 4k. Substitution of the mercapto group with
      other functional groups lost the activity of compound 4a. The stereochemical
      preference at the thiol-attached position was also determined by preparation of
      both isomers of 4a. It was found that the S configuration compound (36b) is
      approximately 100 times more potent than the corresponding R-isomer (36a).

PMID- 11848218
TI  - A convenient synthesis of 1,1-disubstituted 1,2,3,4-tetrahydroisoquinolines via
      Pictet-Spengler reaction using titanium(IV) isopropoxide and acetic-formic
      anhydride.
AB  - A synthesis of 1,1-disubstituted 1,2,3,4-tetrahydroisoquinolines (6) was achieved
      in a highly efficient manner via Pictet-Spengler reaction of arylethylamines (1)
      and acyclic and cyclic ketones (2) using titanium (IV) isopropoxide and acetic
      formic anhydride. The cyclization of the in situ formed acyliminium ion (4) to N
      formyl 1,2,3,4-tetrahydroisoquinoline (5) was greatly facilitated by using
      trifluoroacetic acid as an additional reagent. The Pictet-Spengler reaction was
      carried out by one pot procedure, providing a convenient and effective method for
      preparing various 1,2,3,4-tetrahydroisoquinolines.

PMID- 11848219
TI  - Association of tannins and related polyphenols with the cyclic peptide gramicidin
      S.
AB  - The association of 10 different tannins and related polyphenols with gramicidin
      S, a cyclic peptide having a rigid beta-turn structure, has been examined using
      1H-NMR spectroscopy. In the presence of pentagalloylglucose and epigallocatechin
      3-O-gallate, the proton signals due to proline and the adjacent phenylalanine
      moieties selectively shifted to up field, suggesting a regioselective association
      with the beta-turn structure. The association was also supported by the
      observation of intermolecular nuclear Overhauser effects between epigallocatechin
      3-O-gallate and the peptide. In contrast, ellagitannins, biogenetically derived
      from pentagalloylglucose, showed small and non-selective chemical shift changes,
      suggesting that interaction with these tannins is relatively weak. The
      hydrophobicity of the tannin molecules and the steric hindrance of the
      interaction site are thought to be important in the association.

PMID- 11848220
TI  - A novel method for estimation of transition temperature for polymorphic pairs in
      pharmaceuticals using heat of solution and solubility data.
AB  - A novel method for thermodynamic stability studies of polymorphic drug substances
      has been developed. In order to estimate the transition temperature for an
      enantiotropic polymorphic pair, a formula for calculating the temperature at
      which the solubilities of each polymorph become equal has been derived with heat
      of solution and solubility as the variables. This formula is based on the
      assumption that van't Hoff plots (logarithmic solubility versus reciprocal of
      absolute temperature plots) of each polymorph show a straight line (heat of
      solution is independent of temperature) whose slope can be expressed as a
      function of heat of solution. The transition temperatures for seratrodast,
      acetazolamide and carbamazepine polymorphic pairs calculated by the formula were
      in good agreement with the results of previous studies. Furthermore, the
      calculated transition temperature for the indomethacin polymorphic pair was above
      the melting point, an unrealistic temperature range, suggesting that these
      polymorphs are monotropically related. Since this formula requires solubility
      data at only one arbitrary temperature other than heat of solution data for both
      polymorphs in a polymorphic pair, the proposed method is much faster than the
      conventional method requiring solubility data at five or more different
      temperatures for the preparation of van't Hoff plots.

PMID- 11848221
TI  - Ent-kaurane diterpenoid glycosides from the leaves of Cussonia racemosa, a
      Malagasy endemic plant.
AB  - Six new ent-kaurane diterpenoid glycosides, cussoracosides A (3), B (4), C (5), D
      (6), E (7), and F (8) were isolated from the dried leaves of Cussonia racemosa,
      along with two known compounds identified as beta-D-glucopyranosyl ent-16beta,17
      dihydroxykauran-19-oate (1) and paniculoside IV (2). The structures of these new
      compounds were deduced on the basis of chemical and spectroscopic evidence.

PMID- 11848222
TI  - Synthesis and pharmacological analysis of high affinity melatonin receptor
      ligands.
AB  - We report the synthesis and radioligand binding analysis of a series of
      naphthalenic melatonin receptor ligands, N-[2-(7-alkoxy-2-methoxy-1
      naphthyl)ethyl]propionamide. This series of ligands exhibits subpicomolar binding
      affinity to both MT1 and MT2 melatonin receptors expressed in chinese hamster
      ovary (CHO) cells.

PMID- 11848223
TI  - Constituents of the roots of Rubia yunnanensis.
AB  - Four new naphthohydroquinones, rubinaphthins A (1), B (2), C (3), and D (4),
      together with 11 known compounds were isolated and characterized from the roots
      of Rubia yunnanensis. The structures of 1-4 were elucidated by spectral analysis
      and chemical transformation.

PMID- 11848224
TI  - HPLC analysis of manno-oligosaccharides derived from Saccharomyces cerevisiae
      mannan using an amino column or a graphitized carbon column.
AB  - The chromatographic behavior of manno-oligosaccharides derived from Saccharomyces
      cerevisiae mannan on two kinds of HPLC columns, an aminopropyl-silica column or a
      graphitized carbon column (GCC), was investigated. The order of elution of manno
      oligosaccharides on both columns with acetonitrile-water was almost the same,
      that is, the retention increased with increasing molecular size. However, the GCC
      made it possible to isolate completely two isomers of mannotrioses (M(3)-1 and
      M(3)-2) with different linkage positions. We reinvestigated the structures of
      mannobiose (M(2)), M(3)s, and mannotetraose (M(4)) that were completely isolated
      by matrix-assisted laser desorption ionization time-of-flight mass spectrometry
      (MALDI-TOF-MS) and NMR spectroscopy.

PMID- 11848225
TI  - Four new 26-aminocholestane-type glycosides from Solanum abutiloides.
AB  - From the fresh roots of Solanum abutiloides, four new 26-aminocholesteryl
      glycosides were obtained, and their structures were characterized by analysis of
      their spectra data, including two-dimensional (2D) NMR spectroscopy. These
      compounds were regarded as key intermediates in the biogenesis of steroidal
      alkaloids.

PMID- 11848227
TI  - New mu-opioid receptor agonists with phenoxyacetic acid moiety.
AB  - New muq-opioid receptor (MOR) agonists containing 4-hydroxypiperidine, piperidine
      and piperazine moieties were synthesized and evaluated to find a peripheral
      opioid analgesic. Among the synthesized compounds, 12-[1-[3-(N,N
      dimethylcarbamoyl)-3,3-diphenylpropyl]-4-hydroxypiperidin-4-yl]phenoxy]acetic
      acid (8: SS620) having phenoxyacetic acid and 4-hydroxypiperidine moieties showed
      the highest agonist potency on the MOR in an isolated guinea-pig ileum
      preparation, and it also had selectivity to the human MOR expressed in Chinese
      hamster ovary (CHO)-K1 cells compared with the same types of delta- and kappa
      opioid receptors (DOR and KOR). In addition, compound 8 showed a 10 times more
      potent MOR agonist activity than loperamide. Furthermore, compound 8 showed a
      peripheral analgesic activity in vivo screening on rat.

PMID- 11848226
TI  - Preparation of optically active allothreonine via optical resolution by replacing
      crystallization.
AB  - An attempt was made to use a simple procedure to obtain D- and L-allothreonine (D
      and L-aThr), which are non-proteinogenic alpha-amino acids and are useful as
      chiral reagents in asymmetric syntheses. DL-aThr that exists as a conglomerate
      was optically resolved by replacing crystallization with L-alanine (L-Ala) as an
      optically active co-solute. D-aThr was preferentially crystallized from an
      aqueous solution of DL-aThr in the presence of L.-Ala, as was L-aThr in the
      presence of D-Ala. Furthermore, a diasteroisomeric mixture of D-aThr and L
      threonine (L-Thr) and one of L-aThr and D-Thr were prepared, respectively, by
      epimerization of L- and D-Thr using salicylaldehyde as the catalyst in acetic
      acid. Based on the result of the replacing crystallization, D- and L-aThr were
      separated from aqueous solutions of the diastereoisomeric mixtures in the
      presence of L- and D-Ala. The partially resolved D- and L-aThr were
      recrystallized from water to yield the corresponding enantiomers in optically
      pure forms.

PMID- 11848228
TI  - Synthesis of 2,2'-dihydroxybisphenols and antiviral activity of some bisphenol
      derivatives.
AB  - New diphenylmethane-type 2,2'-dihydroxybisphenols (5a-d) were prepared
      regioselectively in good yields. We evaluated the antiviral activity of some
      bisphenol derivatives synthesized by the plaque reduction assay. Most of the
      compounds showed significant antiviral activity and the 4,4'-dihydroxybisphenol
      derivative (10) showed higher activity than 2,2'-bisphenol derivatives. This
      compound had EC50 value of 1.8 microg/ml.

PMID- 11848230
TI  - Determination of the absolute stereostructure of seco-macrosphelide E produced by
      a fungal strain from a sea hare.
AB  - seco-Macrosphelide E has been isolated from a strain of Periconia byssoides
      originally separated from the sea hare Aplysia kurodai. Its absolute
      stereostructure, with the same configuration as that of macrosphelide E, have
      been elucidated on the basis of spectroscopic analyses and unambiguous synthesis.

PMID- 11848229
TI  - Synthesis of 2-amino-3-benzyl-5-(p-hydroxyphenyl)pyrazine.
AB  - 2-Amino-3-benzyl-5-(p-hydroxyphenyl)pyrazine (2), a precursor of Watasenia
      preluciferin (coelenterazine) (1), is widely distributed in marine bioluminescent
      animals. It was prepared from p-hydroxyphenylglyoxal aldoxime (5) in two steps;
      by condensation with or-aminophenylpropiononitrile in the presence of TiCl4 in
      pyridine, followed by reduction of the resulting N-oxide (6) with Zn-AcOH in
      CH2Cl2 and produced 2, with an 89% overall yield. This procedure was linked with
      the facile one-step preluciferin synthesis reported in the previous paper. Thus,
      Watasenia preluciferin (1), frequently required for various chemiluminescent and
      bioluminescent studies, was coveniently synthesized in three steps from 5, with a
      56% overall yield, overcoming the difficulty of obtaining it from natural
      sources.

PMID- 11848231
TI  - One-pot preparation of chiral beta-amino esters by rhodium-catalyzed three
      components coupling reaction.
AB  - Chiral beta-amino esters are synthesized in one-pot from three components,
      amines, aldehydes, and ethyl bromoacetate, under the rhodium-catalyzed
      Reformatsky-type reaction condition, where complete diastereoselection is
      achieved in the nucleophilic addition step of ethyl bromoacetate to the imines
      prepared in

PMID- 11848233
TI  - Pedestrians who required admission to hospital after collisions with motor
      vehicles in Sweden from 1987 to 1994.
AB  - OBJECTIVES: To report the incidence, range of injury, medical consequences, and
      mortality of pedestrians in collisions with motor vehicles in Sweden. DESIGN:
      Retrospective case study. SETTING: The Swedish Hospital Discharge Register
      (SHDR). SUBJECTS: 8684 pedestrians in collisions with motor vehicles had a total
      of 12,036 episodes treated in Swedish hospitals from 1987-1994. INTERVENTIONS:
      Statistical analysis of the Register. MAIN OUTCOME MEASURES: Incidence of
      pedestrians in collisions with motor vehicles in Sweden, mortality, range of
      injuries, and medical consequences. RESULTS: From 1987 to the end of 1994, a
      total of 8684 pedestrians were admitted to Swedish hospitals after collisions
      with motor vehicles. A mean of 17.6 persons were admitted/100,000
      population/year. In all there were 12,036 admissions of injured pedestrians.
      There were 4593 men (53%) and 4091 women (47%), with a median age of 47 (range 1
      100) years. The annual incidence of injured pedestrians (both men and women)
      decreased significantly during this period. Injuries to the extremities were
      commonest (39% fractures), followed by injuries to the head and neck (34%). The
      total number of deaths in our series of patients was 444 (5%). Of these, more
      than half had head injuries, 22% had fractures, and 5% abdominal or thoracic
      injuries. CONCLUSION: The number of pedestrians in collisions with motor vehicles
      is low in Sweden. Injuries to the extremities were commonest, followed by
      injuries to the head and neck. Old people were most likely to be injured and 5%
      of the patients treated in hospital died.

PMID- 11848232
TI  - Effects of aminoguanidine and N(omega)-nitro-L-arginine methyl ester on vascular
      hyporeactivity induced by endotoxaemia.
AB  - OBJECTIVE: To investigate the effects of endotoxaemia on the reactivity of the
      aortic bed in rats, and to compare the effects of the nitric oxide (NO) synthase
      inhibitors aminoguanidine and N(omega)-nitro-L-arginine methyl ester (L-NAME), on
      endotoxaemia-induced changes in vascular reactivity. DESIGN: Randomised
      experiment. SETTING: University laboratory, Turkey. SUBJECTS: 54 Wistar rats.
      INTERVENTIONS: Rats were divided into control (n = 24) and endotoxaemia (n = 30)
      groups and were treated with an intraperitoneal injection of saline (control) and
      lipopolysaccharide (20 mg/kg), respectively. Subgroups of control and
      endotoxaemic rats were given either aminoguanidine or L-NAME by the same route.
      MAIN OUTCOME MEASURES: Contractile responses to phenylephrine and relaxation
      responses to acetylcholine 4 hours after treatment. RESULTS: Incubation with
      aminoguanidine and L-NAME potentiated the phenylephrine-induced contractile
      response and inhibited acetylcholine-induced relaxation in aortic rings in the
      control group. The vascular responses to phenylephrine and acetylcholine were
      less pronounced in the endotoxaemia group, and in vitro incubation with
      aminoguanidine and L-NAME partially restored the contraction induced by
      phenylephrine but did not affect the impaired response to acetylcholine.
      Aminoguanidine given in vivo prevented the impairment of vascular responses to
      both phenylephrine and acetylcholine whereas L-NAME gave no such protection.
      CONCLUSION: Aminoguanidine acted similarly to L-NAME when incubated with the
      tissues in vitro, and did not show selectivity to inducible compared with
      constitutive isoforms of NO synthase. The finding that aminoguanidine but not L
      NAME, prevented the endotoxin-induced impairment of vascular reactivity when
      administrated in vivo, therefore, suggested a role other than inhibition of NO
      synthase.

PMID- 11848234
TI  - Surgery for recurrent goitre: its complications and their risk factors.
AB  - OBJECTIVE: To find out the morbidity of reoperation for benign recurrent thyroid
      disease, and the risk factors associated with it. DESIGN: Retrospective study.
      SETTING: Specialist endocrine unit, Germany. SUBJECTS: 1031 patients operated on
      for recurrent goitre between 1 January 1983 and 31 December 1996. MAIN OUTCOME
      MEASURES: Incidence of recurrent laryngeal nerve palsy and hypocalcaemia.
      RESULTS: 82/1031 patients were excluded from assessment for recurrent laryngeal
      nerve function leaving 949 for analysis. There were no cases of bilateral
      permanent palsy, but 1 patient developed temporary bilateral palsy. 33 patients
      (3%) developed permanent unilateral palsy and 46 (5%) temporary palsy. 1307
      nerves were at risk, and the rate of permanent palsy was therefore 2% of nerves
      at risk. This was 5 times the rate after the initial operation. Hyperthyroidism
      and not exposing the nerve during operation were predisposing factors. 118
      patients were excluded from assessment of hypocalcaemia leaving 913 for analysis.
      23 patients developed temporary hypocalcaemia (2%), but only 5 (0.5%) developed
      permanent hypocalcaemia. Because so few patients developed hypocalcaemia we were
      unable to designate risk factors. CONCLUSION: Because of the high risk of
      complications operations for recurrent goitre should be done only if the patient
      cannot be treated in any other way. The risk of recurrence should be minimised by
      excision of all nodules during the initial operation.

PMID- 11848235
TI  - Modified technique for correction of gynaecomastia.
AB  - OBJECTIVE: To test a modification of the circumareolar incision for correction of
      a gynaecomastia from the points of view of complications and appearance of the
      scar. DESIGN: Clinical study. SETTING: Military and university hospitals, Turkey.
      SUBJECTS: 32 patients with gynaecomastia operated on between 1992 and 2000.
      INTERVENTIONS: Simon I patients were treated with an inferior semicircular
      periareolar incision (n = 12). Half of the Simon II patients had the same
      incision and the others were treated with a modified extended incision (n = 10 in
      each group). MAIN OUTCOME MEASURES: Haematoma, skin necrosis, nipple inversion,
      low-seated nipple, asymmetry, hypoaesthesia and hypertrophic scar. RESULTS: Simon
      II patients treated with the unmodified incision had more haematomas and seromas
      than Simon I patients and worse cosmesis (p = 0.009 and p = 0.02). However, the
      complication rates did not differ significantly compared with the Simon II
      patients who had the modified incision. CONCLUSION: A modified extended
      circumareolar incision results in fewer complication and better cosmesis in grade
      II gynaecomastia than the standard incision.

PMID- 11848236
TI  - Efficacy of subcutaneous and topical local anaesthesia for pain relief after
      resection of malignant breast tumours.
AB  - OBJECTIVE: Infiltration and topical application of local anaesthetics close to
      the surgical wound may be used to prevent postoperative pain. We evaluated the
      efficacy of these treatments after breast surgery for cancer. DESIGN: Double
      blind randomised trial with two treatment groups and one control group. SETTING:
      University hospital, Sweden. INTERVENTIONS: Patients were allocated to treatment
      with bupivacaine infiltration (n = 29), topical application of
      lignocaine/prilocaine (n = 31), or no local treatment (n = 30). MAIN OUTCOME
      MEASURES: Difference and time related patterns in pain scores measured on a
      visual analogue scale (VAS), and morphine consumption. RESULTS. None of the local
      anaesthetics significantly reduced the VAS score or morphine consumption.
      However, fewer patients in the anaesthetic groups had high VAS scores than
      controls, the 75 centile for the mean score after operation being 2.7, 2.0 and
      2.1 for the controls, infiltration, and topical anaesthetic groups, respectively.
      The controls had higher scores from 6 hours postoperatively onwards. The
      corresponding median morphine consumption was 24.5, 18.5, and 16.2 mg.
      CONCLUSIONS. Local anaesthesia slightly reduced the overall pain scores and the
      morphine consumption, but was of potential clinical value only in the patients
      who had the highest pain scores.

PMID- 11848237
TI  - Effect of acute limb ischaemia on neuromuscular function in rats.
AB  - OBJECTIVE: To locate the exact site of the primary lesion in the neuromuscular
      system in acutely ischaemic extremities. DESIGN: Experimental study. SETTING:
      University hospital, Greece. ANIMALS: 22 adult rats. INTERVENTIONS: Isometric
      tensions of extensor digitorum longus muscles were recorded before ischaemia and
      every 5 minutes after the arterial occlusions by indirect stimulation. When no
      contractile activity was elicited, the muscle was stimulated directly and
      recordings made every 5 minutes. The sciatic nerve function was checked by
      recordings of nerve conduction velocity. Specimens from the muscles were examined
      under electron microscopy. MAIN OUTCOME MEASURES: Muscle contractile properties,
      conduction velocity, and electron microscopic appearance. RESULTS: After a period
      of about 50 minutes neuromuscular function under indirect stimulation in the
      ischaemic limbs was lost, whilst under direct stimulation the extensor digitorum
      longus muscles and the sciatic nerves still functioned. Electron microscopic
      study showed distinct alterations at the neuromuscular junctions. CONCLUSIONS:
      The response of the neuromuscular system to acute ischaemia indicated that the
      neuromuscular junction is probably the site most susceptible to acute ischaemia.

PMID- 11848238
TI  - Percutaneous endoscopic gastrostomy for nutrition in patients with oesophageal
      cancer.
AB  - OBJECTIVE: To evaluate the technical aspects and risks of using percutaneous
      endoscopic gastrostomy (PEG) in the treatment of patients with oesophageal
      cancer. DESIGN: Retrospective study. SETTING: Teaching hospital, Sweden.
      SUBJECTS: 229 consecutive patients who presented with oesophageal cancer between
      January 1990 and the end of December 1999. INTERVENTION: Insertion of a PEG after
      diagnosis and before treatment. MAIN OUTCOME MEASURES: Morbidity and mortality.
      RESULTS: PEGs were successfully inserted in 222/229 (97%), and the tumour
      required dilatation in 103 (45%). There was 1 oesophageal perforation and 1 tear
      of the stomach wall, both of which resulted in death (mortality 0.9%). In 1
      operated patient the right gastroepiploic artery was injured by the PEG, but this
      did not prevent the stomach being used successfully as the oesophageal
      substitute. PEGs were removed because of leaks in 2 patients. There was 1
      possible implantation metastasis. CONCLUSION: PEG is a safe and a well tolerated
      way of ensuring enteral nutrition in patients with oesophageal cancer. The risk
      of the PEG complicating any later operation is minimal.

PMID- 11848239
TI  - Energy expenditure during treadmill walking before and after vertical banded
      gastroplasty: a one-year follow-up study in 11 obese women.
AB  - OBJECTIVE: To find out whether weight reduction induced by vertical banded
      gastroplasty (VBG) alters the energy expenditure in severely obese women during
      treadmill walking. DESIGN: A prospective one year follow-up study, patients being
      their own controls. SETTING: University hospital, Sweden. SUBJECTS: A consecutive
      series of 11 women who had VBG. MAIN OUTCOME MEASURES: Indirect calorimetry, body
      mass index (BMI), preset and comfortable walking speeds, heart rate, perceived
      exertion, and quality of life. RESULTS: 11 patients were evaluated. Mean BMI
      (kg/ml) decreased from 41 (range 36-46) before to 32 (range 25-37) 12 months
      postoperatively. The energy expenditure decreased significantly both at
      comfortable and preset walking speeds. The comfortable walking speed increased
      from 2.7 km x h(-1) (range 1.3-3.4) before operation to 3.8 (range 2.0-4.2) one
      year postoperatively (p = 0.003). All bodily variables in the SF-36 questionnaire
      showed improvement from 6 months onwards. CONCLUSION: Weight reduction in women
      reduces the energy expenditure during walking both at comfortable and preset
      speeds. The comfortable walking speed is increased. The improvements are
      reflected in the patients' own assessment.

PMID- 11848241
TI  - Factors that affect recurrence after incisional herniorrhaphy with prosthetic
      material.
AB  - OBJECTIVE: To evaluate the risk factors for recurrence after prosthetic
      incisional herniorrhaphy. DESIGN: Retrospective study. SETTING: Tertiary referral
      centre, Spain. PATIENTS: 246 patients who had incisional herniorrhaphy with a
      prosthetic material (polypropylene) between 1990 and 1997 INTERVENTIONS: A
      reinforcement mesh was inserted when the hernia was more than 5 cm. In incisional
      hernias less than 5 cm the reinforcement mesh was inserted when the repair was
      under tension or when tissues were noted to be weak during the operation. MAIN
      OUTCOME MEASURES: Age, sex, obesity, the presence of bronchial disease, previous
      repair of the incisional hernia, type of surgery, size and site of hernia and
      presence of local complications during the immediate postoperative period.
      RESULTS: Mean (SD) follow-up was 77 (6) months (minimum follow up two years). The
      hernia recurred in 43 cases (17%) (mean time of recurrence 10 (8) months). Age
      over 60 years, previous herniorrhaphy, size of hernia, and postoperative local
      complications were significant risk factors (p < 0.01) in both the univariate and
      multivariate analyses. CONCLUSIONS: Patients at the greater risk of recurrence
      are those aged over 60 years, with large, recurrent hernias and who develop local
      complications during the postoperative period.

PMID- 11848240
TI  - Feasibility of local infiltration anaesthesia for recurrent groin hernia repair.
AB  - OBJECTIVE: To describe the the feasibility of and patients' satisfaction with day
      case repair of recurrent inguinal hernias under unmonitored local anaesthesia.
      DESIGN: Prospective study. SETTING: Public service university hospital, Denmark.
      SUBJECTS: All patients with a reducible recurrent inguinal or femoral hernia
      unselectedly referred for elective repair during the 4-year period 1 September
      1994 to 31 August 1998. INTERVENTIONS: Data were collected prospectively and
      consecutively from standardised, detailed files, a questionnaire 4 weeks
      postoperatively, and the Copenhagen Hospitals electronic patient data management
      system. MAIN OUTCOME MEASURES: Feasibility of local anaesthesia in the day case
      setting, patient satisfaction and morbidity. RESULTS: 215 consecutive operations
      for recurrent hernias were performed under unmonitored local anaesthesia. No
      conversion to general anaesthesia took place and no patients developed urinary
      retention. After 207 operations, the patients were discharged on the day of
      operation (96%), and the median time from the end of operation to discharge was
      90 minutes (IQR 75-140). After 6 operations (3%), patients had complications that
      required surgical intervention. The 4-week questionnaire was returned after 208
      operations (97%). 30 patients were dissatisfied, mainly because of intraoperative
      pain (17 patients, 8%). No mortality or cardiopulmonary morbidity was recorded
      during the first 30 days postoperatively. CONCLUSIONS: Open day-case repair of
      recurrent inguinal hernias can safely be conducted under unmonitored local
      anaesthesia with minimal morbidity. Intraoperative pain is the main topic that
      requires improvement.

PMID- 11848242
TI  - Granular cell breast tumour: diagnosis and outcome.

PMID- 11848243
TI  - Cystic phaeochromocytoma presenting as an acute abdomen with shock.

PMID- 11848244
TI  - Metastases of predominantly dopamine-secreting phaeochromocytoma that did not
      accumulate meta-iodobenzylguanidine: imaging with whole body positron emission
      tomography using 18F-labelled deoxyglucose.

PMID- 11848245
TI  - Abdominal wall metastasis after open resection of an adrenocortical carcinoma.

PMID- 11848246
TI  - Necrosis of a colonic graft after oesophageal replacement: early diagnosis by
      automated air tonometry.

PMID- 11848247
TI  - Inguinal herniorrhaphy with an undetached strip of external oblique aponeurosis:
      old or new?

PMID- 11848248
TI  - Isolated blunt traumatic gallbladder injury.

PMID- 11848249
TI  - Dilated cardiomyopathy in Presa canario dogs: ECG findings.
AB  - Forty-seven Presa canario dogs were diagnosed with congestive heart failure due
      to dilated cardiomyopathy (DCM). Supraventricular or ventricular
      tachydysrhythmias were found in 29 dogs. Atrial fibrillation was the most common
      dysrhythmia. Ventricular dysrhythmias were observed infrequently and had a very
      important prognostic value in Presa canario dogs with DCM. Abnormalities of
      cardiac conduction were diagnosed in 16 (34%) dogs and changes in wave morphology
      were found in 29 (62%) dogs. Normal sinus rhythm was recorded in only 12 (26%)
      Presa canario dogs with DCM.

PMID- 11848250
TI  - Comparative pharmacokinetics of theophylline in camels (Camelus dromedarius) and
      goats (Caprus hircus).
AB  - A comparative randomized crossover study was conducted to determine the
      pharmacokinetics of theophylline in male and female camels (Camelus dromedarius)
      and goats (Caprus hircus). Theophylline is an established 'probe drug' to
      evaluate the drug metabolizing enzyme activity of animals. It was administered by
      the intravenous (i.v.) route and then intramuscularly (i.m.) at a dose of 2
      mg/kg. The concentration of the drug in plasma was measured using a high
      performance liquid chromatography (HPLC) technique on samples collected at
      frequent intervals after administration. Following i.v. injection, the overall
      elimination rate constant (lambda z,) in goats was 0.006 +/- 0.00076/min and in
      camels was 0.0046 +/- 0.0008/min (P < 0.01). The elimination half-life (t 1/2
      lambda z) in goats (112 .7 min) was lower than in camels (154.7 min) (P < 0.01).
      The apparent volume of distribution (Vz) and the total body clearance (Cl) in
      goats were 1440.1 +/- 166.6 ml/kg and 8.9 +/- 1.4 ml/min/kg, respectively. The
      corresponding values in camels were 1720.3 +/- 345.3 ml/kg and 6.1 +/- 1.0
      ml/min/kg, respectively. After i.m. administration, theophylline reached a peak
      plasma concentration (Cmax) of 1.8 +/- 0.1 and 1.7 +/- 0.2 microg/ml at a post
      injection time (Tmax) of 67.5 +/- 8.6 and 122.3 +/- 6.7 min in goats and camels,
      respectively. The mean bioavailability (T) in both goats and camels was 0.9 +/-
      0.2. The above data suggest that camels eliminate theophylline at a slower rate
      than goats.

PMID- 11848251
TI  - Prediction of the oocyte recovery rate in the bitch.
AB  - In order to investigate the possibility of predicting the recovery rate of
      oocytes for use in a sperm-zona pellucida binding assay, ovaries were obtained
      from 67 bitches of 37 different breeds, and cumulus-oocyte complexes (COCs) were
      recovered by mincing the ovaries with a scalpel. The mean number of COCs
      recovered was 37.2 +/- 34.1 (range 0-145) per ovary. Age significantly affected
      COC recovery rates. From bitches 1-6 years old, 54.2 +/- 35.1 COCs/ovary were
      recovered, compared to 26.4 +/- 29.0 from bitches 7-13 years old (P = 0.003). The
      morphology of the uterus or the presence or absence of ovarian structures had no
      significant effect on COC recovery rates, although there was a tendency for more
      COCs to be recovered from ovaries with only follicles visible on the surface.
      There were no significant correlations between body weight or ovarian weight and
      COC recovery rates. There was a high correlation in the COC recovery rate between
      the two ovaries of a bitch, enabling an approximate estimation of the COC
      recovery rate from the second ovary when the COCs from the first ovary have been
      recovered. The large variation in COC recovery rates between bitches stresses the
      need for storage of canine oocytes in order to secure a high enough number of
      oocytes for a homologous sperm-zona pellucida binding assay in the dog.

PMID- 11848252
TI  - Effect of Nigella sativa on glucose concentration, lipid peroxidation, anti
      oxidant defence system and liver damage in experimentally-induced diabetic
      rabbits.
AB  - This study was carried out to investigate whether Nigella sativa could decrease
      the lipid peroxidation, increase the anti-oxidant defence system and also prevent
      the lipid-peroxidation-induced liver damage in experimentally induced diabetic
      rabbits. Fifteen New Zealand male rabbits were divided into three experimental
      groups: control, diabetic and diabetic and N. sativa-treated. The diabetes
      mellitus (DMI) was induced in the rabbits using 150 mg/kg of 10% alloxan. The
      diabetic + N. sativa-treated group was given extract of N. sativa seeds orally
      every day for 2 months after induction of DM. At the end of the 2-month
      experiment, blood samples were collected to measure malondialdehyde (MDA),
      glutathione (GSH), ceruloplasmin and glucose concentration, and livers were
      harvested for histopathological analysis. Treatment with N. sativa decreased the
      elevated glucose and MDA concentrations, increased the lowered GSH and
      ceruloplasmin concentrations, and prevented lipid-peroxidation-induced liver
      damage in diabetic rabbits. It was concluded that N. sativa might be used in
      diabetic patients to prevent lipid peroxidation, increase anti-oxidant defence
      system activity and also prevent liver damage.

PMID- 11848253
TI  - Efficacy of a herd-specific vaccine against Staphylococcus aureus to prevent post
      partum mastitis in dairy heifers.
AB  - A placebo-controlled field study was performed to evaluate the effect of a herd
      specific vaccine against Staphylococcus aureus on intramammary infection (IMI),
      somatic cell count (SCC) and clinical mastitis. Three hundred and twenty-one
      heifers were assigned to two groups. Heifers in the vaccination group (n = 164)
      were vaccinated twice, i.e. 5 and 2 weeks before their expected calving date.
      Animals of the control group (n = 157) received the same treatment with a placebo
      containing no bacterial antigen. Quarter milk samples were collected immediately
      after parturition prior to the first machine milking, 3-4 weeks after calving and
      before the onset of treatment in animals with signs of clinical mastitis during
      the first 3 months after calving. For comparison of SCC the data from the monthly
      milk test records were evaluated. The prevalence of S. aureus in quarter milk
      samples taken at calving and 3-4 weeks post-partum did not differ significantly
      between the vaccine and control group. Incidence of clinical mastitis during the
      first 3 months after calving and the prevalence of S. aureus in quarter milk
      samples taken before the onset of treatment did not differ significantly between
      the groups. The SCC was lower in vaccinated than in control heifers. However, the
      difference was only significant on the third milk test day. Regarding prevalence
      of IMI with S. aureus and incidence of clinical mastitis the use of a herd
      specific vaccine against S. aureus did not prove to be efficient on this farm.

PMID- 11848254
TI  - Comparison of blood markers for the longitudinal monitoring of osteoclastic
      activity in the pig.
AB  - In the present study the osteoclast activity was monitored longitudinally in
      porcine blood samples by measuring the tartrate-resistant acidic phosphatase
      (TRAP) activity with several methods described for human samples. These methods
      differed in their specificity for bone-specific TRAP and in their practicability.
      The validity of TRAP measurements was evaluated by comparison with the peripheral
      concentrations of the N-terminal fragments of type I collagen with attached cross
      links (NTx), a highly bone-specific parameter of bone collagen degradation, using
      a commercially available test kit developed for human samples. On selected days
      urine samples were collected for the determination of pyridinium cross-links. The
      determinations of cross-links in urine were normalized for the creatinine
      concentrations. However, they were not related to fluoride-sensitive TRAP
      (fsTRAP) and NTx measurements in serum. The fsTRAP activity in serum, which is
      assumed to be highly bone-specific, was highly correlated with the NTx
      concentrations in serum under different experimental conditions. As measurements
      in blood may be more easily standardized than those in urine, fsTRAP measurements
      in serum seem to be a highly practicable method to characterize osteoclastic
      activity in the pig.

PMID- 11848255
TI  - The influence of ventilation mode (spontaneous ventilation, IPPV and PEEP) on
      cardiopulmonary parameters in sevoflurane anaesthetized dogs.
AB  - The purpose of this study was to investigate the cardiopulmonary influences of
      sevoflurane in oxygen at two anaesthetic concentrations (1.5 and 2 MAC) during
      spontaneous and controlled ventilation in dogs. After premedication with fentany
      droperidol (5 microg/kg and 0.25 mg/kg intramuscularly) and induction with
      propofol (6 mg/kg intravenously) six dogs were anaesthetized for 3 h. Three types
      of ventilation were compared: spontaneous ventilation (SpV), intermittent
      positive pressure ventilation (IPPV), and positive end expiratory pressure
      ventilation (PEEP, 5 cm H2O). Heart rate, haemoglobin oxygen saturation, arterial
      blood pressures, right atrial and pulmonary arterial pressures, pulmonary
      capillary wedge pressure and cardiac output were measured. End tidal CO2%,
      inspiratory oxygen fraction, respiration rate and tidal volume were recorded
      using a multi-gas analyser and a respirometer. Acid-base and blood gas analyses
      were performed. Cardiac index, stroke volume, stroke index, systemic and
      pulmonary vascular resistance, left and right ventricular stroke work index were
      calculated. Increasing the MAC value during sevoflurane anaesthesia with
      spontaneous ventilation induced a marked cardiopulmonary depression; on the other
      hand, heart rate increased significantly, but the increases were not clinically
      relevant. The influences of artificial respiration on cardiopulmonary parameters
      during 1.5 MAC sevoflurane anaesthesia were minimal. In contrast, PEEP
      ventilation during 2 MAC concentration had more pronounced negative influences,
      especially on right cardiac parameters. In conclusion, at 1.5 MAC, a surgical
      anaesthesia level, sevoflurane can be used safely in healthy dogs during
      spontaneous and controlled ventilation (IPPV and PEEP of 5 cm H2O).

PMID- 11848256
TI  - Enzyme activities, protein content and cellular variables in the pulmonary
      epithelial lining fluid in selected healthy pigs.
AB  - Reference values of cellular and non-cellular components in the bronchoalveolar
      lavage fluid (BALF) were established from the BALF specimens obtained from 52
      healthy pigs. Using urea as an endogenous marker of dilution, the reference
      values in the epithelial lining fluid (ELF) were calculated: total cell count
      2.71 x 10(9) - 56.49 x 10(9) litre(-1) ELF, alveolar macrophages 2.02 x 10(9) -
      49.91 x 10(9) litre(-1) ELF, lymphocytes 0.10 x 10(9) - 4.74 x 10(9) litre(-1)
      ELF, polymorphonuclear neutrophils 0.01 x 10(9) - 3.48 x 10(9) litre(-1) ELF,
      protein 0.10 - 13.13 g litre(-1) ELF, lactate dehydrogenase 127-1843 Units litre(
      1) ELF, and alkaline phosphatase 86-994 Units litre(-1) ELF. The problems of
      quantification of BALF components are discussed and a standardized lavage
      protocol in swine is described, which is essential for the interpretation of
      diagnostic findings and for the comparison of different BALF specimens.

PMID- 11848257
TI  - Advances in treatment strategies in hypertension: the very-low-dose combination
      first-line.

PMID- 11848259
TI  - Rationale and design of the ADVANCE study: a randomised trial of blood pressure
      lowering and intensive glucose control in high-risk individuals with type 2
      diabetes mellitus. Action in Diabetes and Vascular Disease: PreterAx and
      DiamicroN Modified-Release Controlled Evaluation.
AB  - RATIONALE: Individuals with type 2 diabetes mellitus have an increased risk of
      vascular disease, which is reduced by lowering the blood pressure of patients
      with hypertension. However, the association between blood pressure and vascular
      risk appears to be continuous across a broad range of values of blood pressure,
      and it is likely that blood pressure-lowering will confer similar benefits in
      nonhypertensive individuals. Intensive glucose-lowering in these patients have
      also been shown to reduce microvascular disease, but the effects on macrovascular
      outcomes remain uncertain. OBJECTIVES: To determine the effects on macrovascular
      and microvascular disease of first, lowering blood pressure using a very-low-dose
      angiotensin-converting enzyme (ACE) inhibitor-diuretic combination compared with
      placebo; and second, intensive glucose control targeting a glycated haemoglobin
      A1c concentration of 6.5% or less compared with usual glucose control, in high
      risk hypertensive and non-hypertensive individuals with type 2 diabetes. DESIGN:
      A 2 x 2 factorial randomised, controlled trial with a scheduled period of
      treatment and follow-up of 4.5 years. SETTING: The study will be conducted in
      approximately 200 centres in Australasia, Asia, Europe and North America.
      PARTICIPANTS: The study will include 10000 adults with type 2 diabetes at
      increased risk of vascular disease. Individuals will be eligible irrespective of
      baseline blood pressure, baseline glucose concentration or requirement for
      background ACE inhibitor treatment. INTERVENTIONS: After 6 weeks receiving the
      active perindopril-indapamide combination, eligible individuals will be randomly
      allocated to receive continued very-low-dose perindopril-indapamide combination
      or matching placebo; and to an intensive modified-release gliclazide-based
      glucose control regimen, or usual guidelines-based treatment. STUDY OUTCOMES: The
      primary outcomes are, first, the composite of non-fatal stroke, non-fatal
      myocardial infarction or cardiovascular death and, second, the composite of new
      or worsening nephropathy or diabetic eye disease. Secondary outcomes include
      cause-specific cardiovascular end-points in addition to dementia and all-cause
      mortality.

PMID- 11848258
TI  - Amelioration of arterial properties with a perindopril-indapamide very-low-dose
      combination.
AB  - BACKGROUND: Epidemiological studies have shown that increased arterial stiffness
      and wave reflections, major determinants of systolic and pulse pressure, are
      associated with morbidity and mortality. Therapeutic trials based on
      cardiovascular mortality have recently shown that reduction of systolic blood
      pressure (SBP) requires normalization of both large-artery stiffness and wave
      reflections. AIMS: To compare the antihypertensive effects of the very-low-dose
      combination of perindopril (2 mg) and indapamide (0.625 mg) (one or two tablets
      per day) with the beta-blocking agent atenolol (50 mg; one or two tablets per
      day) in order to determine whether the combination decreased SBP and pulse
      pressure more than did atenolol, and whether this decrease occurred in relation
      to a reduction in arterial stiffness [aortic pulse wave velocity (PWV)] or a
      decrease in the intensity of, or delay in, wave reflections (augmentation index,
      measured by applanation tonometry) or a combination of both. MATERIAL AND
      METHODS: This was a double-blind randomized study in 471 individuals with
      essential hypertension followed for 12 months. Arterial pressure was measured in
      the brachial artery (mercury sphygmomanometer) and in the carotid artery
      (applanation tonometry). RESULTS: For the same reduction in diastolic blood
      pressure (DBP), the combination of perindopril and indapamide decreased brachial
      SBP and pulse pressure significantly more than did atenolol (adjusted differences
      between groups -6.2 +/- 1.5 and -5.5 +/- 1.0 mmHg, respectively; P < 0.001). This
      difference was even more pronounced for the carotid than for the brachial artery.
      Whereas both antihypertensive agents similarly decreased PWV, only the
      combination significantly attenuated wave reflections. CONCLUSION: Normalization
      of SBP, pulse pressure and arterial function--a haemodynamic profile known to
      improve survival significantly in hypertensive populations at high cardiovascular
      risk--was achieved to a greater extent with a very-low-dose combination of
      perindopril and indapamide than with atenolol.

PMID- 11848260
TI  - Healthcare benefits of very-low-dose combination treatment used in the management
      of hypertension.
AB  - There are several classes of effective pharmacological agents available for the
      treatment of hypertension. However, rates of successful blood pressure control
      remain low among treated patients, while antihypertensive medication represents a
      large and increasing proportion of healthcare expenditure in many countries.
      Several influential pharmacoeconomic analyses have confirmed the cost
      effectiveness of conventional antihypertensive treatments, usually involving
      monotherapy using diuretics or beta-blockers, compared with alternative
      strategies. Recent research has shown that a considerable proportion of the total
      cost of antihypertensive treatment in general practice is attributable to factors
      such as inadequate blood pressure control, poor compliance with treatment,
      discontinuation of treatment, and switching between treatments. These factors are
      generally less influential in well-supervised clinical trials, and have not been
      fully incorporated into most economic studies. Some novel strategies,
      particularly the use of low-dose combinations of antihypertensive agents as first
      line therapy, may offer advantages in terms of efficacy, reduced side effects,
      and improved compliance with treatment; these advantages would be predicted to
      result in improved cost-effectiveness. There is therefore a need for
      comprehensive pharmacoeconomic analyses of novel strategies, taking these
      additional factors into account. Until such studies are available, the wider use
      of low-dose combination treatments and other novel strategies should not be held
      back on the basis of findings of earlier economic studies that have not included
      all relevant considerations.

PMID- 11848261
TI  - Rationale for the use of very-low-dose combinations as first-line treatment of
      hypertension.
AB  - The management of hypertension remains a difficult task, despite the availability
      of an increasing number of medications that decrease blood pressure by different
      mechanisms. In order to achieve a blood pressure less than 140/90 mmHg, most
      hypertensive patients require the co-administration of two or more drugs from
      different therapeutic classes. This explains why fixed-dose combinations are
      becoming increasingly popular. Combining drugs with different impacts on the
      cardiovascular system makes it possible to maximise the antihypertensive efficacy
      of the treatment regimen. The combination of very low doses of drugs that exhibit
      dose-dependent side effects leads to a marked gain in efficacy, with
      indiscernible side effects. During recent years, very-low-dose combinations have
      been developed. These combinations are very promising because of their excellent
      efficacy and tolerance profile. This has led to the recognition that such
      combinations might be a valuable option with which to initiate treatment in
      hypertensive patients.

PMID- 11848263
TI  - Effect of water content on transient nonequilibrium NAPL-gas mass transfer during
      soil vapor extraction.
AB  - The effect of water content on the volatilization of nonaqueous phase liquid
      (NAPL) in unsaturated soils was characterized by one-dimensional venting
      experiments conducted to evaluate the lumped mass transfer coefficient. An
      empirical correlation based upon the modified Sherwood number, Peclet number, and
      normalized mean grain size was used to estimate initial lumped mass transfer
      coefficients over a range of water content. The effects of water content on the
      soil vapor extraction SVE process have been investigated through experimentation
      and mathematical modeling. The experimental results indicated that a rate-limited
      NAPL-gas mass transfer occurred in water-wet soils. A severe mass transfer
      limitation was observed at 61.0% water saturation where the normalized effluent
      gas concentrations fell below 1.0 almost immediately, declined exponentially from
      the initiation of venting, and showed long tailing. This result was attributed to
      the reduction of interfacial area between the NAPL and mobile gas phases due to
      the increased water content. A transient mathematical model describing the change
      of the lumped mass transfer coefficient was used. Simulations showed that the
      nonequilibrium mass transfer process could be characterized by the exponent beta,
      a parameter which described the reduction of the specific area available for NAPL
      volatilization. The nonequilibrium mass transfer limitations were controlled by
      the soil mean grain size and pore gas velocity, were well described by beta
      values below 1.0 at low water saturation, and were well predicted with beta
      values greater than 1.0 at high water saturation.

PMID- 11848262
TI  - Clinical benefit of very-low-dose perindopril-indapamide combination in
      hypertension.
AB  - OBJECTIVE: To review the efficacy and safety of the very-low-dose combination of
      2 mg perindopril and 0.625 mg indapamide in essential hypertension. STUDY
      SELECTION: The five main studies from the European registration file were
      performed in hypertensive outpatients and included two phase II double-blind
      randomised dose-ranging studies, and three phase III double-blind randomised
      studies (one study comparing placebo with each of the components, one long-term
      study over 15 months and one study comparing the combination and losartan). MAIN
      OUTCOME MEASURES: Decreases in systolic (SBP) and diastolic (DBP) blood pressures
      measured at trough with a mercury sphygmomanometer, an automatic device (Omron),
      and 24 h ambulatory blood pressure measurements (ABPM). RESULTS: The combination
      2 mg perindopril and 0.625 mg indapamide was selected from the dose-finding
      studies. Twelve weeks after participants in the randomised studies were allocated
      to groups, the reductions in SBP, measured with an Omron device, were 12.3 +/-
      15.0 mmHg with the combination, 8.0 +/- 16.5 mmHg with 2 mg perindopril (P =
      0.001), 9.4 +/- 14.3 mmHg with 0.625 mg indapamide (P = 0.023), and 2.1 +/- 16.8
      mmHg with placebo (P < 0.001) (mean +/- SD; all P values are for comparisons with
      the combination). The reductions in DBP were 6.8 +/- 9.2 mmHg, 5.0 +/- 9.5 mmHg
      (P = 0.02), 4.7 +/- 8.2 mmHg (P = 0.004), and 2.4 +/- 9.6 mmHg (P < 0.001) in the
      combination, 2 mg perindopril, 0.625 mg indapamide and placebo groups,
      respectively. During the long-term study, among 235 patients who achieved initial
      blood pressure normalisation with the fixed combination, 79.8% sustained their
      normalisation over 1 year, with no significant difference regarding safety
      criteria: the occurrence of adverse drug reactions per patient per year was 0.37
      and 0.28 in the combination and placebo groups, respectively. A significantly (P
      < 0.05) larger blood pressure decreasing effect on nocturnal mean SBP (by ABPM)
      was demonstrated for the combination compared with that achieved with losartan,
      with no difference in safety. CONCLUSIONS: The proven efficacy on DBP and SBP,
      and the good safety profile, confirm that the new low-dose combination of 2 mg
      perindopril and 0.625 mg indapamide is a valuable option in the first-line
      treatment of hypertension.

PMID- 11848264
TI  - Electrokinetic ion transport through unsaturated soil: 2. Application to a
      heterogeneous field site.
AB  - Results of a field demonstration of electrokinetic transport of acetate through
      an unsaturated heterogeneous soil are compared to numerical modeling predictions.
      The numerical model was based on the groundwater flow and transport codes MODFLOW
      and MT3D modified to account for electrically induced ion transport. The 6-month
      field demonstration was conducted in an unsaturated layered soil profile where
      the soil moisture content ranged from 4% to 28% (m3 m(-3)). Specially designed
      ceramic-cased electrodes maintained a steady-state moisture content and electric
      potential field between the electrodes during the field demonstration. Acetate, a
      byproduct of acetic acid neutralization of the cathode electrolysis reaction, was
      transported from the cathode to the anode by electromigration. Field
      demonstration results indicated preferential transport of acetate through soil
      layers exhibiting higher moisture content/electrical conductivity. These field
      transport results agree with theoretical predictions that electromigration
      velocity is proportional to a power function of the effective moisture content. A
      numerical model using a homogeneous moisture content/electrical conductivity
      domain did not adequately predict the acetate field results. Numerical model
      predictions using a three-layer electrical conductivity/moisture content profile
      agreed qualitatively with the observed acetate distribution. These results
      suggest that field heterogeneities must be incorporated into electrokinetic
      models to predict ion transport at the field-scale.

PMID- 11848265
TI  - Estimation of local scale dispersion from local breakthrough curves during a
      tracer test in a heterogeneous aquifer: the Lagrangian approach.
AB  - The local scale dispersion tensor, Dd, is a controlling parameter for the
      dilution of concentrations in a solute plume that is displaced by groundwater
      flow in a heterogeneous aquifer. In this paper, we estimate the local scale
      dispersion from time series or breakthrough curves, BTCs, of Br concentrations
      that were measured at several points in a fluvial aquifer during a natural
      gradient tracer test at Krauthausen. Locally measured BTCs were characterized by
      equivalent convection dispersion parameters: equivalent velocity, v(eq)(x) and
      expected equivalent dispersivity, [lambda(eq)(x)]. A Lagrangian framework was
      used to approximately predict these equivalent parameters in terms of the spatial
      covariance of log(e) transformed conductivity and the local scale dispersion
      coefficient. The approximate Lagrangian theory illustrates that [lambda(eq)(x)]
      increases with increasing travel distance and is much larger than the local scale
      dispersivity, lambda(d). A sensitivity analysis indicates that [lambda(eq)(x)] is
      predominantly determined by the transverse component of the local scale
      dispersion and by the correlation scale of the hydraulic conductivity in the
      transverse to flow direction whereas it is relatively insensitive to the
      longitudinal component of the local scale dispersion. By comparing predicted
      [lambda(eq)(x)] for a range of Dd values with [lambda(eq)(x)] obtained from
      locally measured BTCs, the transverse component of Dd, DdT, was estimated. The
      estimated transverse local scale dispersivity, lambda(dT) = DdT/U1 (U1 = mean
      advection velocity) is in the order of 10(1)-10(2) mm, which is relatively large
      but realistic for the fluvial gravel sediments at Krauthausen.

PMID- 11848266
TI  - Characterization and spatial distribution of heavy metals in sediment from Cedar
      and Ortega rivers subbasin.
AB  - The Cedar and Ortega rivers subbasin is a complex environment where both natural
      and anthropogenic processes influence the characteristics and distributions of
      sediments and contaminants, which in turn is of importance for maintenance,
      dredging and pollution control. This study investigated the characteristics and
      spatial distribution of heavy metals, including lead (Pb), copper (Cu), zinc (Zn)
      and cadmium (Cd), from sediments in the subbasin using field measurements and
      three-dimensional kriging estimates. Sediment samples collected from three
      sampling depth intervals (i.e., 0-0.10, 0.11-0.56 and 0.57-1.88 m) in 58
      locations showed that concentrations of Pb ranged from 4.47 to 420.00 mg/kg dry
      weight, Cu from 2.30 to 107.00 mg/kg dry weight, Zn from 9.75 to 2,050.00 mg/kg
      dry weight and Cd from 0.07 to 3.83 mg/kg dry weight. Kriging estimates showed
      that Pb, Cu and Cd concentrations decreased significantly from the sediment depth
      of 0.10 to 1.5 m, whereas Zn concentrations were still enriched at 1.5 m. It
      further revealed that the Cedar River area was a potential source area since it
      was more contaminated than the rest of the subbasin. Comparison of aluminum (Al)
      normalized metal concentrations indicated that most of the metals within the top
      two intervals (0-0.56 m) had concentrations exceeding the background levels by
      factors of 2-10. A three-dimensional view of the metal contamination plumes
      showed that all of the heavy metals, with concentrations exceeding the threshold
      effect level (TEL) that could pose a threat to the health of aquatic organisms,
      were primarily located above the sediment depth of 1.5 m.

PMID- 11848267
TI  - Investigation of the vadose zone using barometric pressure cycles.
AB  - This paper documents a technique for investigating one-dimensional airflow in the
      vadose zone. Variations in pore gas pressures resulting from barometric cycles
      were measured at depths as great as 180 m in several gas monitoring wells. The
      data were transformed to the frequency domain, enabling comparison with closed
      form analytic expressions of one-dimensional pressure transport in layered porous
      media. The data reveal evidence for vertical fracture flow that was not apparent
      from in situ measurements of permeability. The data also reveal that the basalt
      underlying the site at depths greater than 100 m has permeability exceeding 1000
      darcies, and is vented to the atmosphere at an estimated distance of a few
      kilometers from the site.

PMID- 11848268
TI  - Electrokinetic ion transport through unsaturated soil: 1. Theory, model
      development, and testing.
AB  - An electromigration transport model for non-reactive ion transport in unsaturated
      soil was developed and tested against laboratory experiments. This model assumed
      the electric potential field was constant with respect to time, an assumption
      valid for highly buffered soil, or when the electrode electrolysis reactions are
      neutralized. The model also assumed constant moisture contents and temperature
      with respect to time, and that electroosmotic and hydraulic transport of water
      through the soil was negligible. A functional relationship between ionic mobility
      and the electrolyte concentration was estimated using the chemical activity
      coefficient. Tortuosity was calculated from a mathematical relationship fitted to
      the electrical conductivity of the bulk pore water and soil moisture data. The
      functional relationship between ionic mobility, pore-water concentration, and
      tortuosity as a function of moisture content allowed the model to predict ion
      transport in heterogeneous unsaturated soils. The model was tested against
      laboratory measurements assessing anionic electromigration as a function of
      moisture content. In the test cell, a strip of soil was spiked with red dye No 40
      and monitored for a 24-h period while a 10-mA current was maintained between the
      electrodes. Electromigration velocities predicted by the electromigration
      transport model were in agreement with laboratory experimental results. Both
      laboratory-measured and model-predicted dye migration results indicated a maximum
      transport velocity at moisture contents less than saturation due to competing
      effects between current density and tortuosity as moisture content decreases.

PMID- 11848269
TI  - The contribution of gender-role orientation, work factors and home stressors to
      psychological well-being and sickness absence in male- and female-dominated
      occupational groups.
AB  - The associations of work stress, types of work and gender-role orientation with
      psychological well-being and sickness absence were investigated in a
      questionnaire survey of 588 male and female nurses and 387 male and female
      accountants. We hypothesised that health might be impaired among women working in
      the male-dominated occupation (accountancy), and men in the female-dominated
      occupation (nursing), but that effects might be moderated by job strain
      (perceptions of high demand and low control), work and home hassles, and
      traditional male (instrumentality) and female (expressivity) psychological
      characteristics. Responses were analysed from 172 female and 61 male nurses, and
      from 53 female and 81 male commercial accountants. Female accountants were more
      likely than other groups to have high anxiety scores on the Hospital Anxiety and
      Depression Scales, while male nurses had the highest rates of sickness absence.
      Male nurses and female accountants also reported more work-related hassles than
      did female nurses and male accountants. Men and women in the same occupation did
      not differ in job strain or job social support, but nurses reported greater job
      strain than accountants, due to higher ratings of demands and lower skill
      utilisation. After adjusting for age, sex, occupation, paid work hours and a
      measure of social desirability bias, risk of elevated anxiety was independently
      associated with higher job strain, lower job social support, more work hassles,
      more domestic responsibility, lower instrumentality and higher expressivity. The
      association between sex and anxiety was no longer significant after
      instrumentality had been entered into the regression model. Sickness absence of
      more than three days over the past 12 months was independently associated with
      higher job strain, more work hassles, lower instrumentality and higher
      expressivity. The results suggest that when men and women occupy jobs in which
      they are in the cultural and numerical minority, there may be adverse health
      effects that are gender-specific. Psychological traits related to socially
      constructed gender roles may also be relevant, and mediate in part the
      differences in psychological well-being between men and women.

PMID- 11848270
TI  - Factors determining inpatient satisfaction with care.
AB  - The objective of the study was to identify factors associated with satisfaction
      among inpatients receiving medical and surgical care for cardiovascular,
      respiratory, urinary and locomotor system diseases. Two weeks after discharge,
      533 patients completed a Patient Judgments Hospital Quality questionnaire
      covering seven dimensions of satisfaction (admission, nursing and daily care,
      medical care, information, hospital environment and ancillary staff, overall
      quality of care and services, recommendations/intentions). Patient satisfaction
      and complaints were treated as dependent variables in multivariate ordinal
      polychotomous and dichotomous logistic stepwise regressions, respectively.
      Patient sociodemographic, health and stay characteristics as well as
      organization/ activity of service were used as independent variables. The two
      strongest predictors of satisfaction for all dimensions were older age and better
      self-perceived health status at admission. Men tended to be more satisfied than
      women. Other predictors specific for certain dimensions of satisfaction were:
      married, Karnofsky index more than 70, critical/serious self-reported condition
      at admission, emergency admission, choice of hospital by her/himself, stay in a
      medical service, stay in a private room, length of stay less than one week, stay
      in a service with a mean length of stay longer than one week. The factors
      associated with inpatient satisfaction elucidated in this study may be helpful in
      interpreting patient satisfaction scores when comparing hospitals, services or
      time periods, in targeting patient groups at risk of worse experiences and in
      focusing care quality programs.

PMID- 11848271
TI  - Sister cities and easy passage: HIV, mobility and economies of desire in a
      Thai/Lao border zone.
AB  - It is recognised that people movement can increase potential risk of HIV
      transmission. In recent years, mobile populations moving across national borders
      have become a focus for HIV/AIDS prevention campaigns. These programs generally
      target border "hot zones" that produce high levels of HIV vulnerability due to
      the degree of mobility and the risk behaviours fostered by these marginal
      environments. However, high degrees of movement and social exploitation need not
      be the only criteria for borders to exacerbate HIV vulnerability. The types of
      social interactions promoted by mobility take many forms. In this paper we
      consider a border zone between Thailand and Laos to show that the links between
      movement and HIV vulnerability are not confined to stereotypical instances of
      coercion and exploitation. Rather we demonstrate that HIV risk in this area is a
      product of both a sense of community and a sense of difference that together
      foster a range of interactions based on mobility back and forth across the
      border. As HIV/AIDS prevention programs increasingly control forms of sexual
      interaction, the border provides a practical and symbolic opportunity to
      establish new forms of sexual relationship falling outside these constraints.
      This tendency to move outside bounds is not limited to border areas but has
      implications for prevention programs everywhere.

PMID- 11848272
TI  - Altruistic willingness to pay in community-based sales of insecticide-treated
      nets exists in Nigeria.
AB  - The objective of this study was to determine whether households who are willing
      to pay for insecticide-treated nets (ITNs) for themselves are prepared to
      contribute for the ITNs to be purchased for the indigent community members who
      cannot afford the nets. This was in the framework of community-based and directed
      sales for ITNs. The study was conducted in four malaria holoendemic communities
      in south-eastern Nigeria. Contingent valuation method was used to determine the
      altruistic willingness to pay (WTP) from randomly selected household heads or
      their representatives, which was elicited using an open-ended question.
      Theoretical validity was assessed using the Tobit model. Median altruistic WTP
      ranged from $0.11 to $0.21 across the four communities (95 Naira = $1). However,
      using a pooled data from the four communities, the mean was $0.34. In Tobit
      estimation, altruistic WTP varied significantly with two of the communities; the
      respondents were resident in, sex, marital status and the amount of savings of
      the respondent. It also varied significantly with the respondents' WTP for their
      own ITNs and average monthly household expenditures to treat malaria (p<0.05).
      Altruistic WTP will exist in community-based and directed sales of ITNs. Thus
      there can be intra-community subsidisation by the rich for the poor who may not
      be able to pay for the nets. Community mobilisation and sensitisation should be
      used to encourage able households to actually pay at least the amounts they have
      stated.

PMID- 11848273
TI  - Companions through cancer: the care given by informal carers in cancer contexts.
AB  - This paper explores the care-giving experiences of informal carers in cancer
      contexts, drawing on both quantitative and qualitative data generated in a 3 year
      study in the UK on the psychosocial needs of cancer patients and their main
      carers. The study adopted a sociological approach to psychosocial needs, in
      contrast to dominant psychological and psychiatric perspectives on such needs in
      psycho-oncology. Data collection methods involved a descriptive cross-sectional
      survey of carers (an achieved sample of 262 respondents, with similar numbers of
      male and female carers) followed by in-depth guided interviews with a sub-sample
      of surveyed carers (n = 32). Key findings are presented in three sections: (i)
      the characteristics of the survey and interview samples; (ii) the examination of
      the care work undertaken by informal carers; and (iii), the exploration of the
      emotion work undertaken by informal carers. CARE WORK FINDINGS: additional care
      work demands were an important feature of informal carers' experiences, although
      this varied with the stage of the patient's disease and with the presence of
      either co-morbidity in patients or morbidity in carers. Specific groups of carers
      expressed the need for help with particular practical tasks and with the personal
      effects of the burden of care work. EMOTION WORK FINDINGS: carers of either
      gender worked hard to manage the emotions of the patient as well as their own
      feeling states, and these aspects of emotion work were intimately connected.
      Carers felt that they had to be, and often wanted to be, strong' and 'positive',
      and to try to maximise the sense of 'life carrying on as normal'. In doing this
      emotion work, carers, especially spousal carers, often symbolically shared in the
      illness and presented the struggle with cancer as a joint one. A concluding
      section considers the significance of our findings for cancer service provision.

PMID- 11848274
TI  - Inequalities in the transition of cerebrovascular disease mortality in New South
      Wales, Australia 1969-1996.
AB  - With reference to epidemiological transition theory, this paper examines change
      in cerebrovascular disease mortality in Australia's most populous state in the 28
      year period, 1969-1996. The hypotheses were that in the context of overall stroke
      mortality decline over the period, marital status, occupational status and
      spatial differences decreased. However, while overall mortality declined,
      differentials increased. The reasons for this are considered, with particular
      implications for epidemiological transition theory and for the targeting of
      populations at risk in policy terms.

PMID- 11848276
TI  - Gender similarities in doctors' preferences--and gender differences in final
      specialisation.
AB  - This article is based on a career history study of gender differences and
      similarities in recruitment to and transitions between specialities among
      Norwegian doctors. A questionnaire on career and family history was sent to all
      Norwegian doctors authorised in 1980-1983. Descriptive statistics and logistic
      regression were used to describe and analyse completion of specialisation in the
      specialty in which they started their career. Survival analysis was used to
      analyse transitions between medical specialities. The findings clearly contradict
      the idea that the low proportion of women in male dominated areas of medicine
      reflects women's lack of interest in specialities like surgery and internal
      medicine. Women were as likely as men to start their career in these fields. The
      problem is their not completing specialist training. A far higher proportion of
      men than women completed their specialist training in surgery. The reasons for
      this are complex. Heavy work loads with duties and "nights on call" make it
      difficult for women to combine childcare and work and make them change to other
      specialities. Also, female specialists in surgery and internal medicine postpone
      having their first child compared to women in other medical specialities.
      However, the fact that some women change from surgery to gynaecology and
      obstetrics, a specialty which to a considerable extent are comparable with
      surgery with regard to duty and work loads, indicate that structural barriers in
      combining childcare and a hospital career do not fully explain the flux of women.
      The possible existence of other closure mechanisms in surgery, as indicated by
      some doctors in this and in other studies, have to be further explored.

PMID- 11848275
TI  - Income, income inequality and health: what can we learn from aggregate data?
AB  - It has been suggested that, especially in countries with high per capita income,
      there is an independent effect of income distribution on the health of
      individuals. One source of evidence in support of this relative income hypothesis
      is the analysis of aggregate cross-section data on population health, per capita
      income and income inequality. We examine the empirical robustness of cross
      section analyses by using a new data set to replicate and extend the methodology
      in a frequently cited paper. The estimated relationship between income inequality
      and population health is not significant in any of our estimated models. We also
      argue there are serious conceptual difficulties in using aggregate cross-sections
      as a means of testing hypotheses about the effect of income, and its
      distribution, on the health of individuals.

PMID- 11848277
TI  - Worlds apart: a comparison between physical activities among youth in Glasgow,
      Scotland and Dunedin, New Zealand.
AB  - Against the background of increasing concern about levels of physical activity
      among young people, this paper reports the results of a cross-national comparison
      between two longitudinal studies of young people in Glasgow, Scotland and
      Dunedin, New Zealand, which used similar methods of assessment at 15 and 18 years
      of age. The comparison revealed that, on average, young people in Dunedin
      participated in a greater range of activities, encompassing both organised sports
      and informal activities such as cycling, and with greater frequency than those in
      Glasgow at both ages, but particularly so at age 18. The difference was
      especially marked for females, among whom one in three in Glasgow reported no
      physical activity at all at age 18. By contrast, in both sexes among those who
      did participate, much less difference in levels of involvement was observed
      between the two locations. Of 35 activities, only in respect of soccer, and only
      for males, did participation and involvement in Glasgow exceed that of Dunedin.
      Neither climatic factors, natural features of the environment, socio-economic
      composition, nor different proportions in single-sex/co-educational schooling
      explain the difference in levels of participation between the two locations.
      Participation rates in selected physical activities do, however, reflect
      different opportunity structures in Dunedin and Glasgow, with an advantage
      accruing to the former in respect of both school and post-school provision.
      Cultural factors, which underpin such differences, also appear to have an
      additional influence on participation, most notably in relation to the gender gap
      in physical activities, much bigger in Glasgow than Dunedin. To redress these
      differences requires an increase in levels of participation generally,
      particularly among females, which depends as much on a shift in values about
      physical activity as on the provision of better resources.

PMID- 11848278
TI  - Gender differences in mental health: evidence from three organisations.
AB  - It is commonly observed that women report higher levels of minor psychiatric
      morbidity than men. However, most research fails to control for the gendered
      distribution of social roles (e.g. paid work and domestic work) and so does not
      compare men and women in similar positions. In this short report, we examine the
      distribution of minor psychiatric morbidity (measured by the 12 item General
      Health Questionnaire) amongst men and women working in similar jobs within three
      white-collar organisations in Britain, after controlling for domestic and
      socioeconomic circumstances. Data from self-completion questionnaires were
      collected in a Bank (n = 2,176), a University (n = 1,641) and the Civil Service
      (n = 6,171). In all three organisations women had higher levels of minor
      psychiatric morbidity than men, but the differences were not great; in only the
      Civil Service sample did this reach statistical significance. We conclude that
      generalisations about gender differences in minor psychiatric morbidity can be
      unhelpful, as these differences may vary depending on the context of the study.

PMID- 11848279
TI  - Reproductive rights and the state in Serbia and Croatia.
AB  - The global reproductive rights movement arose in the late 1980s and early 1990s
      as a challenge to the population control paradigm that has dominated family
      planning policy for almost half a century. The essence of the challenge is to
      place women into the center of population discussions as subjects, not objects of
      policy, and to reorient family planning and health programs toward meeting the
      broad reproductive health needs of individuals, rather than the narrow population
      control objectives of states. Reproductive rights advocates argue that the use of
      family planning programs for developmentalist-oriented population control
      objectives is illegimate, and inevitably relegates women to the status of
      depersonalized policy "targets". The cases of Croatia and Serbia, the two
      dominant partners in the former Federal Republic of Yugoslavia, offer interesting
      twists on these reproductive rights issues. In Croatia and Serbia, unlike in many
      nations, the governments are deliberately seeking to increase rather than
      decrease fertility levels. Moreover, the objective concerns identity politics,
      more so than development: the governments have encouraged increased fertility to
      safeguard the survival of their nations and to strengthen national power amidst
      threatening internal and external environments of ethnic conflict. In this paper,
      we examine the dynamics of pro-natalist fertility policy in Croatia and Serbia.
      We do so with a view to explaining why, despite similarities, the two have
      followed divergent paths. While reproductive rights violations have occurred in
      both nations, they have been markedly higher in Serbia than Croatia. To explain
      this divergence we look at a series of sociopolitical factors, including the
      space available for groups to mobilize in each political system; the degree of
      nationalistic extremism present in the discourse of central political leaders;
      and perceptions of threats and opportunities in external geopolitical
      environments. In conducting this analysis we seek to drive home the point that a
      nation's reproductive rights situation and prospects cannot be understood
      divorced from its sociopolitical context. We also raise an additional impetus for
      promoting the reproductive rights agenda--one largely unexplored in the family
      planning literature-that emerges from low fertility nations facing identity
      issues. Women's bodies must be protected not only against those states seeking to
      use their reproductive capacities for developmentalist-oriented fertility
      control, but also against those wanting their bodies for nationalistic-oriented
      fertility promotion.

PMID- 11848280
TI  - Intratumoral cancer chemotherapy and immunotherapy: opportunities for nonsystemic
      preoperative drug delivery.
AB  - The recent literature documents the growing interest in local intratumoral
      chemotherapy as well as systemic preoperative chemotherapy with evidence for
      improved outcomes using these therapeutic modalities. Nevertheless, with few
      exceptions, the conventional wisdom and standard of care for clinical and
      surgical oncology remains surgery followed by radiation and/or systemic
      chemotherapy, as deemed appropriate based on clinical findings. This, in spite of
      the fact that the toxicity of conventional systemic chemotherapy and
      immunotherapy affords limited effectiveness and frequently compromises the
      quality of life for patients. Indeed, with systemic chemotherapy, the oncologist
      (and the patient) often walks a fine line between attempting tumour remission
      with prolonged survival and damaging the patient's vital functions to the point
      of death. In this context, it has probably been obvious for more than 100 years,
      due in part to the pioneering work of Ehrlich (1878), that targeted or localized
      drug delivery should be a major goal of chemotherapy. However, there is still
      only limited clinical use of nonsystemic intratumoral chemotherapy for even those
      high mortality cancers which are characterized by well defined primary lesions
      i.e. breast, colorectal, lung, prostate, and skin. There has been a proliferation
      of intratumoral chemotherapy and immunotherapy research during the past two to
      three years. It is therefore the objective of this review to focus much more
      attention upon intratumoral therapeutic concepts which could limit adverse
      systemic events and which might combine clinically feasible methods for localized
      preoperative chemotherapy and/or immunotherapy with surgery. Since our review of
      intratumoral chemoimmunotherapy almost 20 years ago (McLaughlin & Goldberg 1983),
      there have been few comprehensive reviews of this field; only one of broad scope
      (Brincker 1993), three devoted specifically to gliomas (Tomita 1991; Walter et
      al. 1995; Haroun & Brem 2000), one on hepatomas (Venook 2000), one concerning
      veterinary applications (Theon 1998), and one older review of dermatological
      applications (Goette 1981). However, none have shed light on practical
      opportunities for combining intratumoral therapy with subsequent surgical
      resection. Given the state-of-the-art in clinical and surgical oncology, and the
      advances that have been made in intratumoral drug delivery, minimally invasive
      tumour access i.e. fine needle biopsy, new drugs and drug delivery systems, and
      preoperative chemotherapy, it is timely to present a review of studies which may
      suggest future opportunities for safer, more effective, and clinically practical
      non-systemic therapy.

PMID- 11848281
TI  - Aminated gelatin as a nasal absorption enhancer for peptide drugs: evaluation of
      absorption enhancing effect and nasal mucosa perturbation in rats.
AB  - This study was carried out to evaluate the potential of aminated gelatin as a
      nasal absorption enhancer for peptide drugs. The absorption-enhancing effect was
      investigated in rats using insulin and fluorescein isothiocyanate-dextran with a
      molecular weight of 4.4 kDa (FD-4) as model drugs. The absorption of insulin was
      estimated by measuring the changes in plasma glucose levels following intranasal
      administration, and that of FD-4 was determined by measuring its plasma
      concentration after dosing. The hypoglycaemic effect after intranasal
      administration of insulin with aminated gelatin significantly increased compared
      with that after intranasal administration of insulin in phosphate buffered
      saline, indicating that aminated gelatin effectively enhanced the nasal
      absorption of insulin. In contrast, neither kind of native gelatin (isoelectric
      point = 5.0 and 9.0) showed any absorption-enhancing effect. The pH of the
      formulations and the concentration of aminated gelatin were found to affect the
      hypoglycaemic effect. In addition, aminated gelatin at a concentration of 0.2%
      significantly enhanced the absorption and the efflux of FD-4 through the rat
      nasal mucosa. The possible perturbation of aminated gelatin to nasal mucosa was
      evaluated by measuring the leaching of lactate dehydrogenase (LDH) using an in
      situ perfusion rat model. Aminated gelatin presented a concentration-dependent
      (0.1-0.4%) but relatively small effect on the LDH leaching from the rat nasal
      epithelial membrane. These results suggest that positively charged aminated
      gelatin could be a new absorption enhancer for nasal delivery of peptide drugs.

PMID- 11848282
TI  - In-vitro cytotoxic/cytostatic activity of anionic liposomes containing
      vinblastine against leukaemic human cell lines.
AB  - Liposomes prepared from lipids dipalmitoylphosphatidylcholine (DPPC) and
      dipalmitoylphosphatidylglycerol (DPPG) with cholesterol were used to investigate
      the percentage of vinblastine encapsulation and the influence of lipid
      composition on the retention properties of vinblastine in buffer as well as in
      cell culture medium. Differential scanning calorimetry (DSC) was applied, to
      study the effect of cholesterol on the phase transition temperature and on the AH
      of the two liposome formulations. The cytotoxic and cytostatic activity of the
      liposome-encapsulated vinblastine was also examined against six leukaemic human
      cell lines. The results showed that encapsulation of vinblastine into liposomes
      was greater than 98% with a drug-phospholipid molar ratio of 0.13-0.18. The major
      improvement in vinblastine retention in buffer as well as in culture medium was
      achieved by employing DPPG. The DSC data showed that vinblastine exerted a more
      perturbing effect in DPPC-cholesterol bilayers than in DPPG-cholesterol bilayers
      and this may explain their lower retention time. The 50% growth-inhibiting (GI50)
      and cytostatic (TGI) activity of liposomal vinblastine did not seem to be
      affected by the type of the liposome while the 50% cytotoxic activity (LC50) was
      affected in four out of the six cell lines tested. The parameters GI50, TGI and
      LC50 were estimated according to the instructions given by the NCI.

PMID- 11848283
TI  - Influence of the composition of in-vitro azo-reducing systems on the degradation
      kinetics of the model compound amaranth.
AB  - The purpose of this study was to investigate the influence of the composition of
      in-vitro azo-reducing systems on the degradation kinetics of the model compound
      amaranth. The degradation kinetics of amaranth were determined under anaerobic
      conditions both in rat caecal content (ex-vivo) and in a variety of in-vitro
      degradation media derived from rat caecal content. It was observed that the
      reducing activity was highly dependent on the preparation method and composition
      of the degradation medium. In pure rat caecal content, the degradation of
      amaranth was apparent first order (k = 0.044 +/- 0.002 min(-1)), while dilution
      of the rat caecal content resulted in an apparent zero-order degradation. Both
      apparent zero- and first-order degradations were also observed in media made up
      of diluted rat caecal content to which cofactors such as NADP, D-glucose-6
      phosphate, glucose-6-phosphate dehydrogenase and Bz were added. This study
      demonstrates that in-vitro azo-reducing kinetics are dependent on the composition
      and mode of preparation of the in-vitro media used. This has to be taken into
      account when evaluating the degradability of azo-aromatic drug delivery systems
      in-vitro.

PMID- 11848284
TI  - Tissue distribution of and species differences in deacetylation of N-acetyl-L
      cysteine and immunohistochemical localization of acylase I in the primate kidney.
AB  - Species differences in the biotransformation of N-acetyl-L-cysteine (NAC) have
      been investigated to evaluate the usefulness of NAC as a constituent in
      parenteral nutrition solutions in place of cysteine. The activity of NAC
      deacetylating enzyme (acylase) was measured in various tissues of different
      species (rat, rabbit, dog, monkey, and man). Acylase activity was highest in the
      kidney in all species studied. Enzyme activity in the liver was 10 %-22 % of that
      in the kidney in the rat, rabbit, monkey, and man, but almost no hepatic activity
      was seen in the dog. NAC-deacetylating activity was very low in other organs. The
      tissue distribution of acylase I was determined by Western blotting and an
      immunohistochemical method employing specific antibody against porcine acylase I
      (EC 3.5.1.14). The immunoblotting study showed a 46-kDa protein band
      corresponding to porcine acylase I in the kidney of all species. In liver
      cytosol, 46 kDa and/or 29 kDa bands were observed in the rat, rabbit, monkey, and
      man, but not in the dog. In the immunohistochemical study, positive staining with
      anti-acylase I antibody was observed clearly in the renal proximal tubules in the
      monkey and man. These results suggested that the kidney and liver were the main
      organs responsible for the biotransformation of NAC to cysteine in mammals other
      than the dog.

PMID- 11848285
TI  - Transport of D-glucose across cultured stratified cell layer of human oral
      mucosal cells.
AB  - To evaluate the role of several specialized mechanisms for D-glucose transport in
      human oral mucosa, a cultured stratified cell layer derived from human oral
      mucosa was employed. Although this culture system has been used for
      reconstructive surgery, we, for the first time, tried to apply this system to the
      evaluation of nutrients and drug transport. Cell number and transepithelial
      electrical resistance (TEER) reached steady state 7-8 days after inoculation on
      the Transwell and TEER values at steady state were 130-140 ohm cm2, which was
      higher or lower than that of small intestine or Caco-2 cells, respectively. The
      transport studies were carried out using the cultured epithelium on the
      Transwell. The transport of D-glucose across the cultured stratified layer of
      oral epithelial cells was much more extensive than L-glucose, and was inhibited
      by 2-deoxy-D-glucose, a substrate of facilitative glucose transporters, and 2
      methyl-D-glucoside, a specific substrate of a Na/glucose cotransporter (SGLT1).
      The results indicate that the sugar transporters function not only to take up D
      glucose by the epithelial cells but also to transport the sugar across the
      stratified epithelial layer.

PMID- 11848287
TI  - Metabolism of sulphobromophthalein II. Species differences between rats, guinea
      pigs and rabbits.
AB  - Interesting species differences in the metabolism of sulphobromophthalein sodium
      have been observed between rats, guinea-pigs and rabbits. The species difference
      was measured in terms of sulphobromophthalein monoglutathione conjugate (mGSH)
      positional isomer formation. After an intravenous injection of
      sulphobromophthalein to rats, 92% of sulphobromophthalein-mGSH excreted into bile
      was the alpha-isomer. In contrast, in guinea-pigs the three isomers alpha, beta
      and delta were excreted in equivalent amounts. In rabbits, the majority of
      sulphobromophthalein-mGSH was excreted as the beta-isomer. The formation ratio of
      glutathione (GSH) conjugates in-vitro using cytosolic glutathione S-transferases
      (GSTs) prepared from livers generally accounted for the biliary excretion ratio
      of alpha-, beta- and delta-monomercaptide isomers in-vivo. GSTs from the livers
      of rat, guinea-pig, and rabbit were purified and characterized. Although their
      main GSTs produced different isomers, their 20 amino acid residues showed that
      they belonged to the same class mu of GSTs. The results suggested differences of
      the three-dimensional structure of GSTs that formed sulphobromophthalein-mGSH
      isomers between the three animal species.

PMID- 11848286
TI  - In-vitro and in-vivo pharmacokinetic interactions of amprenavir, an HIV protease
      inhibitor, with other current HIV protease inhibitors in rats.
AB  - The drug interactions between a new human immune deficiency virus (HIV) protease
      inhibitor, amprenavir, and four other protease inhibitors which are presently
      used have been characterized by in-vitro metabolic studies using rat liver
      microsomal fractions and in-vivo oral administration studies. The metabolic
      clearance rates (Vmax/Km) of amprenavir, saquinavir, indinavir and nelfinavir in
      rat liver microsomes were 50.67+/- 3.77, 170.88 +/- 15.34, 73.01 +/- 2.76 and
      126.06 +/- 6.23 microLmin(-1) (mg protein)(-1), respectively, and the degree of
      metabolicclearance was in the order of saquinavir > nelfinavir > indinavir >
      amprenavir > ritonavir. The inhibition constants (Ki) of ritonavir for
      amprenavir, indinavir, nelfinavir and saquinavir were 2.29, 0.95, 1.01 and 1.64
      microM, respectively, and that of indinavir for amprenavir was 0.67, indicating
      that amprenavir metabolism in rat liver microsomes was strongly inhibited by
      indinavir. The Ki values of amprenavir for indinavir, nelfinavir and saquinavir
      were 7.41, 2.13 and 16.11 microM, respectively, and those of nelfinavirand
      saquinavirforamprenavirwere 9.15 and 34.57 microM, respectively. The area under
      the concentration vs time curve (AUC) of amprenavir after oral co-administration
      with saquinavir, indinavir, nelfinavir or ritonavir (20 mg kg(-1) for each oral
      dose in rats) was increased by 1.6-, 2.0-, 1.2- and 9.1-fold, respectively. The
      AUC values of saquinavir, indinavir and nelfinavir by co-administration with
      amprenavir showed about 7.3-, 1.3-, and 7.9-fold increase, respectively. These
      observations suggested that the oral bioavailability of amprenavir was not so
      affected by co-administration with saquinavir, nelfinavir or indinavir, compared
      with ritonavir, whereas amprenavir markedly affected the oral bioavailability of
      saquinavir and nelfinavir. In addition, the in-vivo effects after co
      administration of two kinds of HIV protease inhibitors cannot always be predicted
      from in-vitro data, suggesting the presence of other interaction processes
      besides metabolism in the liver. However, these results provide useful
      information for the treatment of AIDS patients when they receive a combination
      therapy with two kinds of HIV protease inhibitor.

PMID- 11848288
TI  - Safety toxicity study of plasmid-based IL-12 therapy in Cynomolgus monkeys.
AB  - We have investigated the potential toxicity of hlL-12 DNA plasmid formulated with
      5% polyvinylpyrrolidone (PVP) administered twice weekly via subcutaneous
      injections to Cynomolgus monkeys for four weeks, and have evaluated recovery from
      any effects of the test article over a four-week treatment-free period. Doses of
      the formulated hIL-12 plasmid were selected based on anti-tumour efficacy studies
      previously conducted in mice. The duration of the study and the frequency of
      dosing were designed to support clinical trials. No clinical signs indicative of
      an adverse effect of administration of formulated hIL-12 plasmid were observed.
      There were no apparent effects of the formulated hIL-12 plasmid on body weights
      or on serum chemistry, haematology, coagulation or urinalysis parameters. No
      treatment-elated ocular abnormalities were evident. In addition, examination of
      the electrocardiograms from all monkeys at the pre-study, week-4, and week-8 time
      points did not reveal any treatment-related effects. No treatment-related gross
      lesions were noted at days 28 or 57. Slight histopathological changes associated
      with high doses of PVP vehicle were observed at both time points. These results
      suggested that the administration of formulated hIL-12 plasmid at a dose level up
      to 18 mg kg(-1) dose twice per week for four weeks to experimentally naive
      Cynomolgus monkeys did not result in significant toxicity. These results support
      further testing of this gene therapy in clinical trials.

PMID- 11848289
TI  - Potent apoptotic effects of saponins from Liliaceae plants in L1210 cells.
AB  - We isolated eight saponins, a hexacyclic lanosterol tetraglycoside (1), a 27
      norlanosterol tetraglycoside (2) and six spirostanol oligoglycosides (3-8), from
      the plants of the family Liliaceae. In murine leukaemic L1210 cells, saponins 5
      and 7 at a concentration of 1 microM showed potent cytotoxic activity and the
      activities were in the following decreasing order: 5, 7, 1, 3, 2, 8, 4, 6. At a
      concentration of 10 microM, not only 5 and 7 but also 3 and 8 markedly caused
      cell death. The flow cytometric analysis indicated that 7 and 8 caused a
      concentration- and time-dependent apoptosis of L1210 cells (EC50 value =
      approximately 5 microM). The morphological observation using a light microscope
      revealed that both 7 and 8 induced shrinkage in cell soma and chromatin
      condensation, suggesting apoptotic cell death. Moreover, in agarose gel
      electrophoretic analysis, a typical apoptotic DNA ladder pattern was observed
      after treatment with both 7 and 8. These results suggest that 7 and 8 caused the
      death of L1210 cells through the apoptotic process. These compounds may become
      powerful pharmacological tools for studying the molecular mechanism of apoptosis.

PMID- 11848290
TI  - FR183998, a Na+/H+ exchange inhibitor, suppresses both IL-8 content and
      myocardial infarct size in a cardiac ischaemia-reperfusion model in rats.
AB  - The aim of this study was to determine the effect of FR183998 (5-(2,5
      dichlorothiophen-3-yl)-3-[(2-dimethylaminoethyl)carbamoyl]benzoylguanidine
      dihydrochloride), an Na+/H+ exchange inhibitor, on myocardial interleukin-8 (IL
      8) content and myocardial infarct size in a rat ischaemia and reperfusion model.
      Rats underwent 30 min of ischaemia followed by 1 to 24 h of reperfusion. IL-8
      content rapidly increased in reperfused rat hearts. The maximum increase in IL-8
      was obtained after 3 h of reperfusion. Intravenous administration of FR183998 at
      1 and 3.2 mg kg(-1), 5 min before ischaemia, significantly reduced the IL-8 level
      after 3 h of reperfusion (122 +/- 16 and 149 +/- 23 pg mg(-1) protein,
      respectively), compared with that of the saline-treated group (258 +/- 27 pg mg(
      1) protein). Myeloperoxidase activity after 3 h of reperfusion was also reduced
      by FR183998 (from 0.83+0.19 unit g(-1) weight of tissue in the saline-treated
      group to 0.36 +/- 0.09 and 0.33 +/- 0.06 unit g(-1) weight of tissue in FR183998
      treated groups at 1.0 and 3.2 mg kg(-1), respectively). Myocardial infarction
      induced by 30 min of ischaemia and 24 h of reperfusion was significantly
      suppressed by the same doses of FR183998 (14.0 +/- 1.5,13.5 +/- 1.9% at 1.0 and
      3.2 mg kg(-1)), compared with 22.2+2.7% in the saline-treated group. These
      results suggestthat IL-8 may contribute to the generation of myocardial
      infarction in an ischaemia and reperfusion model in rats.

PMID- 11848291
TI  - Inhibition of CYP3A-mediated oxidation in human hepatic microsomes by the dietary
      derived complex phenol, gallic acid.
AB  - Plant polyphenols, such as gallic acid, have been reported to have a range of
      biological activities including antimutagenic effects. Previously, we reported
      that gallic acid (3,4,5-trihydroxybenzoic acid), an agent found in wine and tea,
      inhibits androstenedione 6beta-hydroxylase activity (Ki 70 microm), a cytochrome
      P450 (CYP3A) marker in human liver microsomes. The pre-incubation of gallic acid
      (100 microM) with human liver microsomes in the absence of NADPH, as compared
      with the presence of NADPH, before assay of androstenedione 6beta-hydroxylase
      activity significantly increased the inhibitory effects of the gallic acid (0.03
      +/- 0.03 nmol (mg microsomal protein)(-1) min(-1) compared with 0.20 +/- 0.06
      nmol (mg microsomal protein) (-1) min(-1) (P < 0.05)). The antioxidant ascorbic
      acid and the radical scavenger glutathione prevented this observed increase in
      inhibition. Removal of gallic acid-derived products from the incubation
      completely restored CYP3A activity. In contrast, the activities of CYP1A and
      CYP2E, and non-CYP mediated reductive microsomal 17beta-hydroxysteroid
      dehydrogenase activity were refractory to inhibition by gallic acid.

PMID- 11848292
TI  - In-vitro distribution of terbinafine in rat and human blood.
AB  - The association of drugs with plasma lipoproteins has the potential to influence
      drug action and disposition. In this study, the uptake and distribution of the
      lipophilic antifungal drug, terbinafine, was investigated in rat and human blood
      and plasma. Fresh plasma was incubated with terbinafine (200-1000 ng mL(-1)),
      then subjected to vertical spin density gradient ultracentrifugation to separate
      protein fractions. The concentrations of terbinafine in each fraction was
      determined using a validated reversed-phase HPLC method. The association of
      terbinafine with very-low-density lipoproteins (15.5 +/- 7.1% of total
      concentration) in human plasma was significantly lower than that associated with
      fractions containing soluble proteins (28.0 +/- 6.2%), high- (26.8 +/- 7.7%) and
      low-density lipoproteins (31.6 +/- 4.6%). In rats terbinafine was found to be
      distributed evenly through plasma protein fractions. The association of
      terbinafine in lipoproteins was independent of concentration (over the range 200
      1,000 ng mL(-1)) and species. The distribution of terbinafine was examined in
      human and rat blood and the blood-to-plasma ratio of terbinafine was 0.70+0.09
      and 1.01 +/- 0.20, respectively, indicating higher association of terbinafine
      with plasma components than erythrocytes in humans. This study suggests that in
      humans and rats, terbinafine associates with a number of plasma proteins
      independently of terbinafine concentration. Alteration in plasma lipoprotein
      concentrations are therefore likely to influence terbinafine binding in blood and
      distribution in the body.

PMID- 11848293
TI  - Comparative inhibitory effects of niflumic acid and novel synthetic derivatives
      on the rat isolated stomach fundus.
AB  - Novel derivatives of 2-[3-(trifluoromethyl)-analino]nicotinic acid (niflumic
      acid) were synthesized. The compounds were compared for their inhibitory effects
      on 5-hydroxytryptamine (5-HT)- and KCI-induced contraction of the rat fundus. The
      aim was to assess structure-activity relationships regarding the selectivity and
      potency of these compounds. Niflumic acid (1-100 microM) concentration
      dependently inhibited 5-HT-induced tonic contractions with an IC50 value
      (concentration reducing the control contractile response by 50%, calculated from
      semi-log graphs) of 0.24 x 10(4) M (n = 9). In contrast, it was significantly
      less potent at inhibiting KCl-induced responses (IC50 = 1.49 x 10(4) M, n = 9).
      The methyl ester (NFAme) and amido (NFAm) analogues showed no selectivity between
      5-HT- and KCl-induced contractions with IC50 values of 1.64 x 10(-4) M (n = 8)
      and 1.87 x 10(-4) M (n = 9) for 5-HT responses, and 2.61 x 10(-4) M (n = 8) and
      2.55 x 10(-4) M (n = 7) for KCl-induced responses, respectively. Our results
      suggest that alteration of the carboxylic acid moiety of niflumic acid reduces
      the selectivity and potency of its inhibitory action on 5-HT-induced contractile
      responses of the rat fundus, possibly via a reduced interaction with calcium
      activated chloride channels.

PMID- 11848294
TI  - General recommendations on immunization. Recommendations of the Advisory
      Committee on Immunization Practices (ACIP) and the American Academy of Family
      Physicians (AAFP).
AB  - This report is a revision of General Recommendations on Immunization and updates
      the 1994 statement by the Advisory Committee on Immunization Practices (ACIP)
      (CDC. General recommendations on immunization: recommendations of the Advisory
      Committee on Immunization Practices [ACIP]. MMWR 1994;43[No. RR-1]:1-38). The
      principal changes include expansion of the discussion of vaccination spacing and
      timing, recommendations for vaccinations administered by an incorrect route,
      information regarding needle-free injection technology, vaccination of children
      adopted from countries outside the United States, timing of live-virus
      vaccination and tuberculosis screening, expansion of the discussion and tables of
      contraindications and precautions regarding vaccinations, and addition of a
      directory of immunization resources. These recommendations are not comprehensive
      for each vaccine. The most recent ACIP recommendations for each specific vaccine
      should be consulted for additional details. This report, ACIP recommendations for
      each vaccine, and other information regarding immunization can be accessed at
      CDCs National Immunization Program website at http.//www.cdc.gov/nip (accessed
      October 11, 2001).

PMID- 11848295
TI  - Neurotensin analogs indications for use as potential antipsychotic compounds.
AB  - This review will be an update, focusing on the central nervous system (CNS) roles
      of the neurotransmitter, neurotensin. We will provide a summary of current
      knowledge about neurotensin, why it is an important peptide to study, and where
      the field is heading. Special emphasis is placed on the development of
      neurotensin analogs, which has been a major effort of our group, the potential
      role of neurotensin in Parkinson's disease, and the interaction of neurotensin
      with other neurotransmitters as evidenced by microdialysis studies.

PMID- 11848296
TI  - Increase on the coronary flow induced by dioclein in isolated rat heart.
AB  - In the present work the effect of dioclein, a new flavonoid from Dioclea
      grandiflora, was investigated in rat hearts. The experiments were performed using
      the classic method of Langendorff, where flow, inotropic, chronotropic and
      electric parameters were analyzed. Bolus administration of Dioclein (1-100
      microg) induced a sustained and dose-dependent increase in coronary flow with no
      modification in inotropic, chronotropic and electrical parameters. The duration
      of increase in coronary flow induced by dioclein (10 microg) was approximately 4
      fold higher than that observed in the presence of sodium nitroprusside (NPS; 10
      microg). Besides, the effect of dioclein measured as the area-under-the-curve was
      approximately 4.5-folds higher than that observed with NPS. Pre-treatment with L
      NAME (100 microM) and indomethacin (10 microM) alone did not modify the effect of
      dioclein (10 microg), suggesting that nitric oxide (NO) and cyclooxygenase
      derived factors were not involved. However, association of L-NAME plus
      indomethacin inhibited the duration of the effect of dioclein (10 microg) without
      changing its increase in the coronary flow. Furthermore, the absence of
      alteration in inotropism and chronotropism of the heart associated with its
      coronary effect suggest that dioclein could be an interesting lead compound for
      the development of drugs for the treatment coronary heart diseases.

PMID- 11848297
TI  - Isolation of a new cyclophilin-like protein from chickpeas with mitogenic,
      antifungal and anti-HIV-1 reverse transcriptase activities.
AB  - A protein designated chickpea cyclophilin-like antifungal protein (CLAP) was
      isolated from seeds of the chickpea (Cicer arietinum). Chickpea CLAP was
      characterized by a molecular weight of 18 kDa and an N-terminal sequence
      homologous to cyclophilins. The protein was isolated with a procedure involving
      affinity chromatography on Affi-gel blue gel and ion exchange chromatography on
      CM-Sepharose. In addition to an inhibitory effect on the growth of fungi
      including Rhizoctonia solani, Mycosphaerella arachidicola and Botrytis cinerea,
      the protein was capable of inhibiting human immunodeficiency virus-1 reverse
      transcriptase. Chickpea CLAP did not possess lectin and ribonuclease activities
      but it weakly inhibited translation in a rabbit reticulocyte lysate system. The
      protein stimulated 3H-thymidine incorporation by mouse splenocytes.

PMID- 11848298
TI  - Effect of ellagic acid on gastric damage induced in ischemic rat stomachs
      following ammonia or reperfusion.
AB  - We examined the effect of ellagic acid (EA), one of the polyphenols that are
      abundantly contained in whisky as a nonalcoholic component, on gastric lesions
      induced by ammonia plus ischemia or ischemia/reperfusion in rats, in relation to
      the antioxidative system. Under urethane anesthesia, a rat stomach was mounted in
      an ex vivo chamber, and the following two experiments were performed; 1) a
      stomach was made ischemic (1.5 ml/100 g body weight) for 20 min, followed by
      reperfusion for 15 min in the presence of 100 mM HCl; 2) a stomach was made
      ischemic by bleeding from the carotid artery (1 ml/100 g body weight), followed
      by intragastric application of ammonia (NH4OH: 120 mM). EA (0.1-10 mg/ml) was
      applied in the chamber 30 min before the onset of ischemia. Gastric potential
      difference (PD) and mucosal blood flow (GMBF) were measured before, during and
      after 20 min of ischemia. Ischemia/reperfusion caused a profound drop in GMBF
      followed by a return, and resulted in hemorrhagic lesions in the stomach in the
      presence of 100 mM HCI. These lesions were dose-dependently prevented by EA with
      suppression of lipid peroxidation but no effect on GMBF, and the effect at 6
      mg/ml was almost equivalent to that of superoxide dismutase (SOD: 15000
      unit/kg/hr) infused i.v. during a test-period. On the other hand, application of
      NH4OH to the ischemic stomach produced a marked reduction in PD, resulting in
      severe hemorrhagic lesions. These changes were prevented with both EA and SOD. In
      addition, EA had a potent scavenging action against monochloramine in vitro.
      These results suggest that EA exhibits gastric protective action against gastric
      lesions induced by NH4OH or reperfusion in the ischemic stomach, probably due to
      its anti-oxidative activity. This property of EA partly explains the less
      damaging effect of whisky in the stomach and may be useful as the prophylactic
      for Helicobacter pylori-associated gastritis.

PMID- 11848299
TI  - Intrathecal [Nphe1]nociceptin( 1-13)NH2 selectively reduces the spinal inhibitory
      effect of nociceptin.
AB  - The effects of intrathecal (i.t.) application of the proposed nociceptin receptor
      antagonist [Nphe1]nociceptin(1-13)NH2 on the flexor reflex was evaluated in
      spinalized rats. I.t. [Nphe1]nociceptin (1-13)NH2 dose-dependently facilitated
      the flexor reflex with no depression. Pretreatment with 16.5 nmol of
      [Nphe1]nociceptin(1-13)NH2 prevented the development of reflex depression
      following 0.55 nmol i.t. nociceptin, but strongly enhance the initial excitatory
      effect of nociceptin. The reflex depressive effect of i.t. endomorphine-2 was not
      blocked by [Nphe1]nociceptin(1-13)NH2 pretreatment. It is concluded that
      [Nphe1]nociceptin(1-13)NH2 is a selective antagonist of the spinal receptor
      mediating the inhibitory action of nociceptin. It can be further suggested that
      the spinal inhibitory effect of nociceptin may be tonically active.

PMID- 11848300
TI  - Functional muscarinic M2 and M3 receptors and beta-adrenoceptor in cultured rat
      bladder smooth muscle.
AB  - A highly purified rat urinary bladder smooth muscle cell culture was obtained by
      a modified enzymic isolation method, and the presence of functional muscarinic as
      well as beta-adrenergic receptors were subsequently determined. At 7-10 days of
      culture, cells became elongated and spindle-shaped showing a typical "hills and
      valleys" form. They were stained with anti-alpha-actin and anti-myosin
      antibodies. Radiolabeled ligand binding using [3H]N-methylscopolamine and
      [3H]CGP12177 showed that these cells expressed muscarinic and beta-adrenergic
      receptors. Stimulation of cultured cells with carbachol inhibited the forskolin
      stimulated cyclic AMP formation, caused an elevation of intracellular Ca2+
      concentration measured by fura-2 fluorometry. The latter response was almost
      completely blocked by 4-DAMP, a selective muscarinic M3 antagonist. On the other
      hand, stimulation of cultured cells with isoproterenol enhanced the basal cyclic
      AMP formation, which was reversed by carbachol. Therefore, the presence of
      functional muscarinic (both M2 and M3) as well as beta-adrenergic receptors was
      confirmed in pure culture of the rat bladder smooth muscle cells obtained by
      using an enzymic isolation method.

PMID- 11848301
TI  - Negative inotropic effects of angiotensin II, endothelin-1 and phenylephrine in
      indo-1 loaded adult mouse ventricular myocytes.
AB  - Angiotensin II (Ang II). endothelin-1 (ET-1) and phenylephrine are receptor
      agonists that share the signal transduction acting through acceleration of
      phosphoinositide hydrolysis in the heart. Because the regulation of myocardial
      contractility induced by these receptor agonists shows a wide range of species
      dependent variation among experimental animals, we carried out experiments to
      elucidate the mechanism of contractile regulation induced by these agents in mice
      which are employed currently more as transgenic models. Effects of Ang II, ET-1
      and phenylephrine on cell shortening and Ca2+ transients were investigated in
      single ventricular myocytes loaded with indo-1/AM. Ang II (10(-8), 10(-7) M), ET
      1 (10(-10), 10(-9) M) and phenylephrine (10(-6), 10(-5) M in the presence of the
      beta-adrenoceptor antagonist timolol) decreased the cell shortening [Ang II:
      58.4+/-9.03 (n = 8), 50.3+/-11.90% (n = 6); ET-1: 48.4+/-8.27, 31.2+/-6.45% (n =
      5); phenylephrine: 45.7+/-11.60, 28.7+/-5.89% (n = 5)]. By contrast, the
      amplitude of Ca2+ transients was not significantly influenced by these agonists.
      The selective protein kinase C inhibitor chelerythrine at 10(-6) M significantly
      inhibited the decrease in cell shortening induced by these receptor agonists.
      These results indicate that Ang II, ET-1 and phenylephrine elicit a negative
      inotropic effect with insignificant alteration of Ca2+ transients, which may be
      mainly mediated by activation of protein kinase C in mouse ventricular
      cardiomyocytes.

PMID- 11848303
TI  - Ethanol-dependent induction of bilirubin UDP-glucuronosyl-transferase in rat
      liver is mediated by Kupffer cells.
AB  - Recently we have reported that bilirubin UDP-glucuronosyltransferase (UGT1A1) is
      induced in rat liver by chronic ethanol treatment. Several studies have shown
      that Kupffer cells play a central role in the mediation of various hepatic
      effects of chronic alcohol consumption. In the present work, the participation of
      Kupffer cells in the ethanol dependent induction of UGT1A1 was investigated. A
      group of rats was pretreated with gadolinium chloride, a known Kupffer-cell
      depleting agent. We compared the effect of chronic ethanol ingestion on UGT1A1
      expression in the liver of normal and gadolinium chloride treated rats. The
      effect of ethanol on bilirubin glucuronidation was completely prevented in
      Kupffer cell deficient rats. The western and northern blot analyses showed that
      the increase of both the protein and mRNA of UGT1A1 was prevented in these
      animals. These results suggest that Kupffer cells play a major role in the
      mediation of ethanol-stimulated induction of UGT1A1 in liver parenchymal cells.

PMID- 11848302
TI  - Inhibition of Ca2+-activated and voltage-dependent K+ currents by 2
      mercaptophenyl-1,4-naphthoquinone in pituitary GH3 cells: contribution to its
      antiproliferative effect.
AB  - Quinones have been shown to possess antineoplastic activity; however, their
      effects on ionic currents remain unclear. The effects of 2-mercaptophenyl-1,4
      naphthoquinone (2-MPNQ), menadione (MD) and 1,4-naphthoquinone (1,4 NQ) on cell
      proliferation and ionic currents in pituitary GH3 lactotrophs were investigated
      in this study. 2-MPNQ was more potent than menadione or 1,4-naphthoquinone in
      inhibiting the growth of GH3 cells. 2-MPNQ decreased cell proliferation in a
      concentration-dependent manner with an IC50 value of 3 microM. In whole-cell
      recording experiments, 2-MPNQ reversibly caused an inhibition of Ca2+-activated
      K+ current (I(K(Ca)) in a concentration-dependent manner. The IC50 value for 2
      MPNQ-induced inhibition of I(K(Ca)) was 7 microM. In the inside-out configuration
      of single channel recording, 2-MPNQ (30 microM) applied intracellularly
      suppressed the activity of large-conductance Ca2+-activated K+ (BK(Ca)) channels
      but did not modify single channel conductance. Menadione (30 microM) had no
      effect on the channel activity, whereas 1,4-naphthoquinone (30 microM) suppressed
      it by about 26%. Both 2-MPNQ and thimerosal suppressed the dithiothreitol
      stimulated channel activity. 2-MPNQ also blocked voltage-dependent K+ currents,
      but it produced a slight reduction of L-type Ca2+ inward current. However, unlike
      E-4031, 2-MPNQ (30 microM) did not suppress inwardly rectifying K+ current
      present in GH3 cells. Under the current clamp configuration, the presence of 2
      MPNQ (30 microM) depolarized the cells, and increased the frequency and duration
      of spontaneous action potentials. The 2-MPNQ-mediated inhibition of K+ currents
      would affect hormone secretion and cell excitability. The blockade of these ionic
      channels by 2-MPNQ may partly explain its inhibitory effect on the proliferation
      of GH3 cells.

PMID- 11848304
TI  - Effects of thymic hormone on reactive oxygen species-scavengers and renal
      function in tacrolimus-induced nephrotoxicity.
AB  - The effects of a thymic hormone (Facteur thymique serique; FTS) on renal reactive
      oxygen species-scavenging enzymes or substances in heminephrectomized rats with
      and without tacrolimus-induced nephrotoxicity were studied. Rats received both
      oral dose of tacrolimus (5 mg/kg/day) and subcutaneous administration of three
      dosages of FTS (5, 50, and 250 microg/kg/day) over 28 days (Group A). In Group B,
      they received three dosages of FTS alone (0.5, 5, and 50 microg/kg/day) or FTS 50
      microg/kg/day with tacrolimus over 28 days. Each dose of FTS (Group A) partially
      elevated renal creatinine clearances. Tacrolimus enhanced renal glutathione
      reductase (GSH-R) activities and glutathione (GSH) and depressed catalase (CAT)
      activities. FTS increased GSH levels and GSH-R activities. Although FTS alone did
      not change CAT activities, CAT activities recovered as a result of concomitant
      use of FTS (Groups A and B). A significant positive correlation was found between
      CAT activity and creatinine clearance. These findings suggest that FTS is useful
      for the prevention of tacrolimus-induced nephrotoxicity, and that the increase of
      renal CAT activity in the defense mechanism of FTS might be important for cell
      protection against active oxygen species.

PMID- 11848305
TI  - Hypertensive.

PMID- 11848306
TI  - Acanthosis nigricans revisited.

PMID- 11848307
TI  - Osteoporosis--current concepts.

PMID- 11848308
TI  - Gender, aging, health and society.
AB  - There are more women than men at any elderly age group. Depression and
      osteoporosis are the commonest problems in elderly subjects. Some problems
      specific to males are hypogonadism, erectile dysfunction and enlargement of
      prostrate and to females are post-menopausal disturbances, urinary incontinence
      and breast and lung cancer. However, problems of special concern in both male and
      female elderly are malnutrition, falls and cognitive dysfunction. Men and women
      in general suffer from the same sorts of health problems but the frequency of
      these problems as well as the speed of the onset of death distinguishes them.
      Infact cultural and social forces act to separate the sexes in their personal
      health ethos and their sick propensity. The impact of old age on women is
      different from that of men because of differences in their status and role in
      society. This is specially so because proportion of widows in 60+ age group is
      considerably higher than that of widowers. Sexuality is often overlooked as a
      health status particularly in elderly women. Clinicians should recognise the
      importance of sexual functions to the overall health of older persons
      particularly women. Religious participation and involvement are associated with
      positive mental and physical health. Family life is the key to the health of
      elders specially older men. Lack of social support increases the risk of
      mortality and supportive relationships are associated with lower illness rates,
      faster recovery rates and higher levels of health care behavior.

PMID- 11848309
TI  - Hepatic abscess caused by Salmonella typhi.
AB  - A 64 years diabetic man presented with recurrent episodes of fever and abdominal
      pain. Ultrasonography revealed the presence of an abscess in the right lobe of
      the liver and a distended gall bladder with multiple calculi. Salmonella typhi
      was grown from the liver aspirate. Cholelithiasis may act as a predisposing
      factor for hepatic abscess formation in Salmonella carriers.

PMID- 11848310
TI  - Diagnostic dilemma in coinfection.
AB  - A Fifteen years girl belonging to a low socioeconomic status was admitted with
      peritonsillar abscess caused by methicillin resistant Staphylococcus aureus
      (MRSA), high fever, diarrhoea and septicaemic shock. Initial blood cultures and
      widal test, stool cultures and routine stool examination were non-contributory to
      the diagnosis. A bone marrow culture in the second week confirmed the diagnosis
      of Salmonella typhi infection. Examination of a fresh stool sample showed cysts
      of Entamoeba histolytica. She was treated with ciprofloxacin, metronidazole,
      augmentin and ceftriaxone. She had no clinical evidence of immunosuppression
      prior to this episode and her HIV test was negative. This case report highlights
      the presence of community acquired MRSA infection causing perititonsillar
      abscess, and the diagnostic dilemma of fever and diarrhoea due to coinfection
      with Salmonella typhi and Entamobea histolytica.

PMID- 11848311
TI  - Isolated symmetrical mediastinal lipomatosis.
AB  - Symmetrical mediatinal lipomatosis is a rare benign condition characterized by
      deposition of a large amount of mature adipose tissue within the mediastinum.
      Usually secondary to exogenous obesity, administration of steroids and Cushing's
      disease, it is more common in middle-aged males and is associated with alcohol
      abuse. Various other associations have been reported. CT and MRI can decisively
      diagnose this benign condition, which also helps in deciding treatment options.
      We present a case of a young female with a bizarre appearance on chest
      radiographs. Isolated, bilaterally symmetrical mediastinal lipomatosis was
      diagnosed on CT and MRI. The patient was thin and did not consume alcohol or
      steroids. Cushing's disease and other known associations were excluded.

PMID- 11848312
TI  - Hemoptysis in musical wind instrument players.
AB  - Three cases of haemoptysis amongst musical wind instrument players encountered in
      last five years are reported. None had an identifiable pathology in lungs.
      Detailed investigations including computed tomography of chest and fibreoptic
      bronchoscopy were normal. Turbulent airflow, frictional trauma to airways due to
      repeated blowing is proposed as the underlying aetio-pathogenesis.

PMID- 11848313
TI  - Myopathy as the sole manifestation of thyroprivic hypothyroidism of autoimmune
      etiology.

PMID- 11848314
TI  - Systemic manifestations in scleredema of Buschke.

PMID- 11848315
TI  - Intracerebral haemorrhage as a complication of enteric fever.

PMID- 11848316
TI  - Primary antiphospholipid syndrome presenting as pseudobulbar palsy in a young
      male.
AB  - Antiphospholipid antibody syndrome (APS) is now recognized as an important risk
      factor for young stroke. Recurrent stroke seems to be common in patients with APS
      and a first stroke, recurrent stroke and vascular dementia are feared
      consequences of APS. We are reporting a case of primary APS with recurrent stroke
      presenting as pseudobulbar palsy in an young man.

PMID- 11848317
TI  - Argemone mexicana and epidemic dropsy: phytopharmacology and putative sequelae
      and therapy.

PMID- 11848318
TI  - Diabetic autonomic neuropathy causing gall bladder dysfunction.

PMID- 11848319
TI  - Hypothalamo-pituitary-adrenal axis function in asthmatics taking low dose inhaled
      beclomethasone dipropionate.

PMID- 11848320
TI  - The changing pattern of multi-drug resistant enteric fever--a physician's
      dilemma.

PMID- 11848321
TI  - Cervical osteophyte induced dysphagia.

PMID- 11848322
TI  - Co-existent extrapulmonary tuberculosis and diffuse non-Hodgkin's lymphoma within
      a lymph node.

PMID- 11848323
TI  - Leukemic ascites.

PMID- 11848324
TI  - Malaria as a cause of multi organ failure.

PMID- 11848325
TI  - Impact of Human Genome Project on medical practice.

PMID- 11848326
TI  - Outbreak of polyarthritis with pyrexia in Western Rajasthan.
AB  - AIM: To establish the etiology of recent out break of polyarthritis which
      occurred in Kanvari village of Churu district of Rajasthan in August, 1999.
      METHODOLOGY: Forty eight patients of polyarthritis were studied by Hb, TDLC, ESR,
      CRP, throat swab Gram's stain and culture, blood culture, ASO titer, rheumatoid
      factor, Rose Bengal plate agglutination test, standard tube agglutination test
      for brucellosis, widal test, urine examination, X-ray chest, ECG and X-ray of the
      affected joint. RESULTS: Forty eight patients presented with acute polyarthritis
      with low grade fever of 1-2 week duration. Most common joint involved was
      sacroiliac joint (52.08%). Most of patients had multiple joint involvement
      (93.75%). The Rose Bengal plate agglutination test and standard tube
      agglutination test for brucella were positive in high titres in 44 (91.60%)
      patients. All the patients were treated with therapy for brucellosis and followed
      up for 12 weeks and responded well without complications. CONCLUSION: In case of
      polyarthritis possibility of brucellosis should always be kept in mind.

PMID- 11848327
TI  - Low dose cyclosporine-a therapy in severe aplastic anaemia.
AB  - OBJECTIVE: The present study was conducted to evaluate the efficacy of low dose
      cyclosporine-A in the patients of severe aplastic anaemia, who cannot afford
      allogenic bone marrow transplantation and immunosuppressive therapy with
      antithymocyte globulin. METHODS: The diagnosis of severe aplastic anaemia was
      established by standard criteria. Twelve patients were given cyclosporine-A
      orally at a dose of 6 mg/kg body weight in divided doses in two daily equal
      proportions for six months. Eleven patients were put on oral stanozolol in the
      dosage of 1 mg/kg body weight/day in divided doses. All surviving patients were
      evaluated at three and six months. RESULTS: At the end of six months, 41.66% of
      twelve patients responded to cyclosporine-A. One patient had complete response
      and four patients had partial response. Only one out of 11 patients receiving
      stanozolol responded. CONCLUSIONS: i) Cyclosporine-A is a viable therapeutic
      option in the treatment of severe aplastic anaemia, ii) Low dose cyclosporine-A
      is able to slow down the stormy course of the severe aplastic anaemia, iii)
      Androgens have very little effect on the survival of patients of severe aplastic
      anaemia.

PMID- 11848328
TI  - Coronary risk and dyslipidemia in type 2 diabetic patients.
AB  - OBJECTIVES: A prospective study was carried out to find out the percentage of
      dyslipidemia in type 2 diabetics, to study the pattern of dyslipidemia,
      categorize the levels of LDL, HDL and triglycerides into higher, borderline and
      lower risk of developing coronary heart disease in type 2 diabetics and to
      compare the lipid profile with non-diabetics. MATERIAL AND METHODS: Five hundred
      patients of type 2 diabetes mellitus and 150 age, sex and BMI matched non
      diabetic healthy individuals were studied. The labelling of dyslipidemia and the
      categorization of risk for developing coronary heart disease (CHD) was done
      according to the guidelines of American Diabetes Association (ADA, 1998).
      RESULTS: Dyslpidemia was present in 89% of diabetic patients with LDL
      hyperlipoproteinemia (LDL > 100 mg%) in 76%, HDL dyslipidemia (HDL < 35 mg%) in
      58%, hypertriglyceridemia (TG > 200 mg%) in 22% patients. On analysing CHD risk
      based on lipid profile, it was revealed that in LDL moiety 48% fell in higher
      risk of CHD (LDL > 130 mg%), 28% in borderline risk (LDL 100-130 mg%) and 24%
      (LDL < 100 mg%) in lower risk. For HDL 18.5% fell in higher risk (HDL < 35 mg%)
      and TG only 0.5% fell in higher risk (TG > 400 mg%). The lipid profile was
      significantly altered in diabetic patients as compared to non diabetics.
      CONCLUSIONS: The major concern which our study highlights is the high percentage
      of LDL dyslipidemia majority of whom fell in higher risk of developing CHD.
      Triglyceride and HDL levels were of lesser significance when newer ADA (1998)
      criteria for dyslipidemia were applied.

PMID- 11848329
TI  - Prevalence of known diabetes in Chennai City.
AB  - AIM: To determine prevalence of known diabetes in those more than 20 years of age
      in Chennai city. METHODOLOGY: Urban population was selected for the survey.
      Assuming the prevalence of known diabetes as 5.0% in those aged > 20 years, the
      cluster sample size calculated to estimate it with 95% CI and +/- 10% precision,
      was 25800 individuals of all ages. This population obtained from 200 households
      in each of 30 randomly selected corporation divisions of the city, was surveyed
      by social workers by house to house enquiry. General information and health
      status of every member of the household were recorded on prescribed forms. This
      survey was conducted during January-July, 1998. RESULTS: Among 26,066 individuals
      of all ages 779 had known diabetes and 99.4% of them had type 2 diabetes. The
      prevalence of known diabetes was 2.9% for all ages and both sexes combined. Crude
      and age-standardized prevalence was 4.9% (95% CI 4.6-5.2) for those aged > 20
      years. The standardized prevalence was 10.5% (95% CI 9.8 - 11.2) in those aged >
      or = 40 years. The prevalence was significantly high (P < 0.05) in females.
      CONCLUSION: The prevalence of known diabetes was low in total population but
      increased in those aged > 20 and further increased in those aged > or = 40 years.
      The causes for high prevalence in > or = 40 year age group needs to be explored
      in this population.

PMID- 11848330
TI  - Prevalence of hepatitis C genotypes in Indian patients and their clinical
      significance.
AB  - AIM: To study the significance of hepatitis C genotypes in relation to severity
      of liver disease, progression of liver disease and response to treatment.
      METHODS: Sixty one consecutive patients with hepatitis C infection were evaluated
      with detailed history, clinical examination, biochemical, imaging and virological
      profile, liver histology whenever feasible. Hepatitis C infection was confirmed
      with AntiHCV third generation ELISA assay. HCVRNA by PCR and HCV genotyping by
      direct sequencing. RESULTS: Demographic profile of patients was as M:F 36:25,
      mean age 46.3 +/- 13.6 years (range 10 to 70 years). Clinical presentations of
      these patients were as cirrhosis 23, cirrhosis with HCC 3, chronic hepatitis 22,
      acute hepatitis 4, asymptomatic with normal enzymes nine. Distribution of
      genotypes was as follows; 13/61 (21%) genotype I, 15/61 (25%) genotypes II and
      33/61 (54%) genotype III. Cirrhosis was significantly common in genotype I (77%)
      when compared to genotype II and III (33%); p < 0.001. Mean time of presenting as
      cirrhosis was much faster in genotype I (8.7 +/- 6.7 years) as compared to other
      genotypes (type II 12.8 +/- 4.2 years and genotype III 15.8 +/- 6.9 years).
      Genotype distribution in CRF and renal transplant patient was genotype I 8/23
      (35%), genotype II 5/23 (22%) and genotype III 10/23 (43%). Fourteen patients
      were treated with interferon and ribavarine combination for one year. Sustained
      response seen in 8/14 (57%). All these patients had genotype non 1. All the four
      patients with Genotype I were non-responders. CONCLUSION: Hepatitis C genotype
      III is common in India, Genotype I runs a more severe course, faster progression
      and non responders to interferon as compared with genotype II and III.

PMID- 11848331
TI  - Plasmapheresis: an adjunct therapy in severe progressive neuropsychiatric lupus.
AB  - OBJECTIVE: We report our experience with use of plasmapheresis (PP) as an adjunct
      therapy in severe progressive neuropsychiatric systemic lupus erythematosus
      (NPSLE). METHOD: Three patients of NPSLE (including 2 with status epilepticus)
      who were progressively worsening on steroids or combination of pulse
      cyclophosphamide (CPM) and steroids were treated with PP followed by synchronized
      CPM. Pre and post treatment SLE Disease Activity Index (SLEDAI) and laboratory
      tests were carried out. RESULTS: Significant clinical improvement with decrease
      in SLEDAI occurred immediately following PP. Mean SLEDAI before and after PP were
      33 and 11. Mean erythrocyte sedimentation rate decreased from 121 to 31. Rebound
      flare of disease activity noted in two patients between 7th-10th day requiring
      additional immunosuppressants or steroids. CONCLUSIONS: PP used as an adjunct
      therapy in severe, progressive NPSLE is well tolerated and can turn the patient
      around. PP should be followed by synchronized pulse CPM to prevent disease flare.

PMID- 11848332
TI  - Parathyroid carcinoma.
AB  - INTRODUCTION: Parathyroid carcinoma is a rare tumor with an incidence of 0.5 to
      4%. Preoperative differentiation from benign adenoma is very difficult. Several
      features, though nonspecific, have been used in differentiating parathyroid
      carcinoma from the adenoma. MATERIAL AND METHOD: A retrospective analysis during
      the period of nine years, four cases of parathyroid carcinoma were diagnosed on
      the basis of per-operative local invasion and on histological evidence of
      capsular invasion and vascular invasion. RESULT: We have different observations
      to make. Diagnosis of parathyroid carcinoma which was done on the basis of intra
      operative suspicion only. One patient died on 6th post operative day due to
      development of pancreatitis. At the follow-up of two years there was no local
      recurrence or distant metastasis. CONCLUSION: It is preferable to have a high
      index of suspicion for parathyroid carcinoma when these features are present than
      to miss the opportunity for surgical cure by failing to consider it in the
      differential diagnosis.

PMID- 11848333
TI  - Impact of human genome project on medical practice.
AB  - The sequence of bases on all 23 pairs of human chromosomes has been nearly
      unravelled. Nearly 3.1 billion nucleotide bases were sequenced using the clone
      based approach of Human Genome Project Consortium and the shotgun approach of
      Celera. There appear to be about 30,000 genes, which are however more complex.
      Human genes seem to have been transferred over evolution from bacteria. Further
      progress is likely in identifying genes and their function, in development of DNA
      chips or arrays to identify genes, expanded field of protomics or the study of
      detailed structure and function of proteins. Pharmacogenomics is possible to
      develop designer drugs depending on the individuals genetic make-up. Projected
      drawbacks from availability of genetic data of individuals include loss of
      privacy, genetic determinism and the risk of high insurance premia, conflict
      about patenting and ownership.

PMID- 11848334
TI  - Biological, psychological and social processes in the conduct disorders.
AB  - BACKGROUND: This paper reviews recent evidence on the causes and maintenance of
      aggressive and disruptive behaviours in childhood and adolescence. It considers
      the relative merits of several different ways of conceptualising such problems,
      in relation to the contribution of biological, psychological and social factors.
      METHOD: It focuses on conduct problems appearing in young childhood, which
      greatly increase the likelihood of persistent antisocial behaviours in
      adolescence and adult life in association with wider interpersonal and social
      role impairments. It considers the contribution of individual factors, including
      impaired verbal skills, deficits in executive functions, and an imbalance between
      behavioural activation and inhibition systems. These are viewed in interaction
      with commonly associated environmental disadvantages such as hostile or intrusive
      parenting. The roles of attributional biases, unrealistic self-evaluations, and
      insecure attachment are considered in relation to affect regulation, and
      effective social action. The contributions of the wider social environments of
      peers, neighbourhood and socio-economic conditions are evaluated. CONCLUSIONS:
      The paper concludes that, although considerable progress has been made over the
      past ten years, there is a need to further refine our conceptualisation of the
      behaviours to be explained, to develop a coherent theory of the causal and
      maintaining processes, and to carry out prospective studies with adequate numbers
      of high risk children.

PMID- 11848335
TI  - Mechanisms of action in youth psychotherapy.
AB  - BACKGROUND: In this review, we address a basic, but unanswered, question about
      psychosocial interventions for youth: How does psychotherapy work? METHODS: We
      propose a framework for using mediation analysis to answer this question, and we
      review the youth therapy outcome literature for evidence on mediating mechanisms.
      We focus our review on clinical trials of empirically supported treatments for
      youth anxiety, depression, and disruptive behavior (N = 67). RESULTS: Contrary to
      previous reports indicating that potential mediators are rarely assessed, 63% of
      the studies included measures of potential mediating mechanisms in their designs.
      Across treatment domains, percentages ranged from 22% of the studies of learning
      based interventions for anxiety (i.e., systematic desensitization, modeling, and
      reinforced practice) to 91% of parent training investigations. Despite the rather
      extensive assessment of potential mediators, only six studies included any
      attempt to use the measures in a formal mediation test. Thus, despite the
      positive effects of treatments and surprisingly ample assessment of mediators, we
      still know remarkably little about how youth psychotherapies work. CONCLUSIONS:
      We note common problems that hampered mediation testing (e.g., the design of many
      trials made it difficult to determine the temporal order of change in the
      mechanism and outcome), and we offer recommendations for improving study design
      to better assess mechanisms of therapeutic action. We also note the need to test
      mediation among referred youth treated in representative practice settings to
      complement the laboratory-based evidence on therapy mechanisms that prevails to
      date.

PMID- 11848336
TI  - Effects of marital conflict on children: recent advances and emerging themes in
      process-oriented research.
AB  - BACKGROUND: The effects of marital conflict on children's adjustment are well
      documented. For the past decade research has increasingly focused on advancing a
      process-level understanding of these effects, that is, accounting for the
      particular responses and patterns embedded within specific contexts, histories,
      and developmental periods that account for children's outcomes over time.
      METHODS: As a vehicle for presenting an update, this review follows the framework
      for process-oriented research initially proposed by Cummings and Cummings (1988),
      concentrating on recent research developments, and also considering new and
      emerging themes in this area of research. RESULTS: In this regard, areas of
      advancement include (a) greater articulation of the effects of specific
      context/stimulus characteristics of marital conflict, (b) progress in identifying
      the psychological response processes in children (e.g., cognitive, emotional,
      social, physiological) that are affected and their possible role in accounting
      for relations between marital conflict and child outcomes, (c) greater
      understanding of the role of child characteristics, family history, and other
      contextual factors, including effects on children due to interrelations between
      marital conflict and parenting, and (d) advances in the conceptualization of
      children's outcomes, including that effects may be more productively viewed as
      dynamic processes of functioning rather than simply clinical diagnoses.
      CONCLUSIONS: Understanding of the impact of marital conflict on children as a
      function of time-related processes remains a gap in a process-oriented
      conceptualization of effects. Based on this review, a revised model for a process
      oriented approach on the effects of marital discord on children is proposed and
      suggestions are made for future research directions.

PMID- 11848337
TI  - The genetic aetiology of childhood depression: a review.
AB  - BACKGROUND: We review the evidence for the familiality of major depressive
      disorder (MDD) and the genetic aetiology of depressive symptoms in children and
      adolescents. METHODS: Databases and reference lists were searched for family,
      twin and adoption studies of childhood MDD and childhood depressive symptoms.
      Data from independent family studies that fulfilled specified inclusion criteria
      were pooled and odds ratios were calculated for top-down and bottom-up family
      studies. RESULTS: Estimates of familial risk differ by control group and by study
      design (odds ratio range 1.70, 3.98). Twin studies show that depressive symptoms
      in young people are heritable although rater and measurement issues are
      important. Adoption studies show little evidence for a genetic influence on
      depressive symptoms. CONCLUSIONS: MDD in young people is familial although
      control group and study design affect the magnitude of the familial risk.
      Estimates of heritability from twin and adoption studies vary widely and few firm
      conclusions can be made regarding the genetic aetiology of depressive symptoms in
      childhood. Areas that require future work include the examination of rater
      effects, measurement issues, the effects of age and comorbidity and reasons for
      the discrepancy between twin and adoption findings.

PMID- 11848338
TI  - Conceptual issues in behavioral teratology and their application in determining
      long-term sequelae of prenatal marihuana exposure.
AB  - BACKGROUND: Behavioral teratology, particularly as it is applied to the
      evaluation of cognition and behavior of children beyond the toddler stage, has
      become an area of burgeoning activity. In the area of drug abuse, children
      exposed in utero are often at developmental peril because of non-drug pre- and
      postnatal risk factors that make a causal association between the drug of
      interest and a behavioral teratogenic outcome increasingly problematic as the
      child gets older. METHODS: In the first portion of this review, the strategies
      that behavioral teratologists have undertaken to investigate the putative
      consequences of in utero exposure are discussed in terms of research design,
      statistical methods and interpretative approaches. In the second part of the
      paper, the relatively limited literature dealing with the behavioral
      teratological consequences of prenatal marihuana exposure, particularly in school
      age offspring, is reviewed. RESULTS: An emergent theme arising from primarily two
      longitudinal investigations is that in utero cannabis exposure does not impact
      upon standardized derived IQ scores but is negatively associated with attentional
      behavior and visual analysis/hypothesis testing. These findings are interpreted
      as supporting the hypothesis that, among offspring beyond the toddler stage,
      prenatal marihuana exposure has a negative influence on aspects of executive
      function. Executive function is a 'top-down', multifaceted cognitive construct
      involved in organizing and integrating specific cognitive and output processes
      over a interval of time and is largely mediated by the late developing,
      prefrontal region of the brain. CONCLUSIONS: The results and the interpretation
      of the prenatal marihuana findings are discussed in terms of the behavioral
      teratogenic effects (or lack of effects) during the various developmental stages
      of the offspring, the non-unitary nature of executive function, cannabis
      receptors, and the consequences of chronic marihuana use in the non-pregnant
      population.

PMID- 11848339
TI  - Phosphorus budget as a water quality management tool for closed aquatic
      mesocosms.
AB  - Since the start-up of the St. Lawrence Mesocosm (SLM) at the Montreal Biodome in
      1992, phosphorus has accumulated slowly, reaching about 18 mg P l(-1) in 2000. It
      was decided that this concentration should be lowered to about 2mg P l(-1) to
      maintain a safe nitrogen:phosporus (N:P) ratio of about 10. Before deciding what
      type of treatment to use for the removal of phosphorus, a P budget was estimated
      for 1998 in order to evaluate the different pathways of phosphorus in the
      mesocosm. The resulting budget had only a 1% difference between the inputs (CV =
      12.9%) and the sum of the outputs and changes in P pools (CV = 12.5%). P inputs
      amounted to 40.5 kg for 1998: food for fish and invertebrates contributed 76% of
      the inputs while seabird guano contributed 20%. Filtration and general cleaning
      removed 51% of the inputs while water losses removed 22%. The slight but constant
      difference between total phosphorus and dissolved reactive phosphorus (DRP) in
      1998 and previous years led us to believe that only DRP (mostly orthophosphate)
      accumulated in the system. The accumulation of DRP was 10% of the inputs in 1998.
      The budget showed that the importance of water losses is relative and depends on
      the DRP concentration in the SLM. Furthermore, it was possible to compare this P
      budget with an N budget of the SLM prepared in 1995. The comparison helped us
      understand why nitrate in closed-circuit mesocosms are characterized by a high,
      never-ending accumulation while DRP is characterized by a net increase in the
      first few years after start-up followed by a very small increase in the following
      years. Considering its low CV, this P budget was considered a useful water
      quality management tool in designing a P removal unit for the SLM. This budget
      may also serve as a guideline for managers of closed-circuit systems such as
      marine aquariums and aquacultures as well as for designers of P removal units.

PMID- 11848340
TI  - Application of a membrane bioreactor for treating explosives process wastewater.
AB  - A bench-scale anoxic membrane bioreactor (MBR) system, consisting of a bioreactor
      coupled to a ceramic cross-flow ultrafiltration module, was evaluated to treat a
      synthetic wastewater containing alkaline hydrolysis byproducts (hydrolysates) of
      RDX. The wastewater was formulated the same as hydrolysis wastewater and
      consisted of acetate, formate and formaldehyde as carbon sources and nitrite and
      nitrate electron acceptors. The MBR system removed 80-90% of the carbon sources,
      and approximately 90% of the stoichiometric amount of nitrate, 60% of nitrite.
      The reactor was also operated over a range of transmembrane pressure,
      temperature, suspended solids concentration, and organic loading rate to maximize
      treatment efficiency and permeate flux. Increasing the transmembrane pressure and
      temperature did not improve flux significantly. Increasing mixed liquor volatile
      suspended solids (MLVSS) concentration in the bioreactor decreased the permeate
      flux significantly. The maximum volumetric organic loading rate was 0.72 kg
      COD/m3/day. The maximum food-to-mass ratio was 0.50 kg N/kg MLVSS/day and 1.82 kg
      COD/kg MLVSS/day. Membrane permeate was clear and essentially free of bacteria,
      as indicated by heterotrophic plate count. Permeate flux ranged between 0.15 and
      2.0 m3/m2 day and was maintained by routine backwashing every three days.
      Backwashing with tap water containing chlorine bleach every fourth or fifth
      backwashing was able to restore membrane flux to its original value.

PMID- 11848341
TI  - Calibration of model constants in a biological reaction model for sewage
      treatment plants.
AB  - Various biological reaction models have been proposed which estimate
      concentrations of soluble and insoluble components in effluent of sewage
      treatment plants. These models should be effective to develop a better operation
      system and plant design, but their formulas consist of nonlinear equations, and
      there are many model constants, which are not easy to calibrate. A technique has
      been proposed to decide the model constants by precise experiments, but it is not
      practical for design engineers or process operators to perform these experiments
      regularly. Other approaches which calibrate the model constants by mathematical
      techniques should be used. In this paper, the optimal regulator method of modern
      control theory is applied as a mathematical technique to calibrate the model
      constants. This method is applied in a small sewage treatment testing facility.
      Calibration of the model constants is examined to decrease the deviations between
      calculated and measured concentrations. Results show that calculated values of
      component concentrations approach measured values and the method is useful for
      actual plants.

PMID- 11848342
TI  - Comparison of different advanced oxidation processes for phenol degradation.
AB  - Advanced Oxidation Processes (O3, O3/H2O2, UV, UV/O3, UV/H2O2, O3/UV/H2O2, Fe2+
      /H2O2 and photocatalysis) for degradation of phenol in aqueous solution have been
      studied in earlier works. In this paper, a comparison of these techniques is
      undertaken: pH influence, kinetic constants, stoichiometric coefficient and
      optimum oxidant/pollutant ratio. Of the tested processes, Fenton reagent was
      found to the fastest one for phenol degradation. However, lower costs were
      obtained with ozonation. In the ozone combinations, the best results were
      achieved with single ozonation. As for the UV processes, UV/H2O2 showed the
      highest degradation rate.

PMID- 11848343
TI  - Wastewater disinfection by ozone: main parameters for process design.
AB  - Wastewater disinfection by ozone was investigated at pilot scale on different
      wastewater effluents. Variations in operating conditions showed that a very low
      hydraulic retention time (2 min) was sufficient for efficient fecal coliform
      inactivation, provided a sufficient ozone dose was transferred to the effluent.
      Therefore, the transferred ozone dose appeared to be the critical parameter for
      the design of wastewater disinfection. As a consequence, the "Ct" approach
      commonly applied in drinking water treatment should not be used for wastewater
      ozonation. Design parameters of ozonation were proposed for two types of
      regulations, and for effluents of different qualities. It was demonstrated that
      only with an efficient filtration step one can meet stringent standards such as
      the California Title 22 criteria. In all cases, viruses were totally inactivated;
      consequently, viruses do not constitute a limiting factor in wastewater
      disinfection by ozone. The standard drinking water model failed to match the
      experimental data obtained on real wastewater effluents. A modified approach was
      successfully developed, based on the simultaneous consumption of ozone by the
      microorganisms and the organic matrix.

PMID- 11848344
TI  - Aerobic moving bed biofilm reactor treating thermomechanical pulping whitewater
      under thermophilic conditions.
AB  - The continuously operated laboratory scale Kaldnes moving bed biofilm reactor
      (MBBR) was used for thermophilic (55 degrees C) aerobic treatment of TMP
      whitewater. In the MBBR, the biomass is grown on carrier elements that move along
      with the water in the reactor. Inoculation with mesophilic activated sludge gave
      60-65% SCOD removal from the first day onwards. During the 107 days of
      experiment, the 60-65% SCOD removals were achieved at organic loading rates of
      2.5-3.5 kg SCODm(-3) d(-1), the highest loading rates applied during the run and
      HRT of 13-22h. Carbohydrates, which contributed to 50-60% of the influent SCOD.
      were removed by 90-95%, while less than 15% of the lignin-like material (30-35%
      of SCODin) was removed. The sludge yield was 0.23g VSSg SCOD(-1)removed. The
      results show that the aerobic biofilm process can be successfully operated under
      thermophilic conditions.

PMID- 11848345
TI  - Effects of high salinity and constituent organic compounds on treatment of photo
      processing waste by a sulfur-oxidizing bacteria/granular activated carbon sludge
      system.
AB  - To achieve practical treatment of photo-processing waste (PW) using our
      previously proposed sulfur-oxidizing bacteria (SOB)/granular activated carbon
      (GAC) sludge system, this paper elucidates why 3- to 5-X dilution of PW was
      required. That is, a series of experiments were carried out to show the effects
      of high salinity and constituent organic compounds in PW, respectively. Both an
      inorganic salts system and calcination PW system showed that SOB completely
      oxidizes S2O(3)2- -S to SO(4)2- -S even at 12.3 or 13.6% salinity, respectively;
      hence the dilution requirement is not attributable to high salinity. In
      experiments employing SOB and SOB/GAC systems to investigate the effects of 23
      constituent compounds in PW, compounds were classified into Groups I, II, IIIa,
      and IIIb. Even with 10 g/l GAC, the nine compounds in Group IIIb still exhibited
      a toxic effect on SOB activity at 1- and 3-X dilutions; thus it is these
      compounds that are responsible for requiring dilution of PW. Accordingly, a
      reduction in their use within the photodeveloping and fix-stabilizing industry,
      and/or use of > 10g/l GAC, are new considerations for establishing a more
      practical PW treatment process.

PMID- 11848346
TI  - The use of upflow anaerobic filter and AnSBR for wastewater treatment at ambient
      temperature.
AB  - This research was carried out in order to study the effect of the temperature and
      hydraulic retention time (HRT) on the start-up and steady-state performance of
      upflow anaerobic filter (UAF) and anaerobic sequencing batch reactor (AnSBR). A
      mixture of synthetic substrate (glucose and sodium acetate) and real municipal
      wastewater was used as a laboratory substrate. The temperature (in the range 9-23
      degrees C) and HRT (in the range 6-46 h) were selected as the most decisive
      technological parameters for a practical application. Average removal efficiency
      of COD found for tested anaerobic reactors were 56-88% (AnSBR) and 46-92% (UAF)
      depending on used temperature and HRTs. Based on the observed results, the use of
      AnSBR and UAF in practice seems to be a potential technology for (pre)-treatment
      of wastewater produced by small communities.

PMID- 11848347
TI  - Determination of haloacetic acids in water by acidic methanol esterification-GC
      ECD method.
AB  - Acidic methanol esterification followed by gas chromatography (GC) with electron
      capture detection (ECD) was applied for the determination of the nine haloacetic
      acids in water. The main advantage of this method is the use of acidic methanol
      as the derivatization agent instead of the hazardous diazomethane. The
      recoveries, estimated at concentrations ranging from 0.5 to 30 microg/l, are high
      for eight of the nine haloacetic acids, with the only exception being
      monochloroacetic acid. However, problems with this compound have been reported
      with diazomethane derivatization methods as well. The detection limits of the
      method range from 0.01 to 0.2 microg/l.

PMID- 11848348
TI  - Removal of organophosphate pesticides from wastewater by supercritical carbon
      dioxide extraction.
AB  - Organophosphate pesticides including fenitrothion chlorpyrifos, diazinon,
      methamidophos, edifenphos, mevinphos, fenthion, and acephate present in agro
      wastewater can be effectively removed by supercritical carbon dioxide (SC-CO2)
      extraction. Near quantitative removal of the pesticides from the aqueous solution
      can be achieved by SC-CO2 at 90 degrees C and 325 atm for 20 min of static
      extraction followed by 40 min of dynamic extraction. The extracted pesticides
      were collected in a small amount of Fenton's solution. The pesticides in Fenton's
      solution were degraded completely within an hour after the collection. A
      combination of SC-CO2 extraction and subsequent degradation by Fenton's reagent
      may provide an alternative water purification strategy for treating
      organophosphate pesticides in agro-wastewater.

PMID- 11848349
TI  - Occurrence of an anthropogenic gadolinium anomaly in river and coastal waters of
      southern France.
AB  - This study reports a pronounced positive Gd anomaly in a small river and in the
      largest French Mediterranean lagoon. Along the studied catchment, this anomaly is
      also present in the effluents of the municipal sewage treatment plants,
      suggesting an anthropogenic origin for the Gd excess. The anomaly corresponds to
      a distinct increase of Gd concentrations (up to 19 pmol/l) in the river and
      around 5.4 pmol/l in the lagoon. The excess flux of Gd is compatible with the
      medical use of water soluble Gd complexes as contrasting agent in magnetic
      resonance imaging.

PMID- 11848350
TI  - Comment on "Oxidation of p-hydroxybenzoic acid by Fenton's reagent" by F.J.
      Rivas, F.J. Belran, J. Frades, and P. Buxeda.

PMID- 11848351
TI  - Formation of N-nitrosodimethylamine (NDMA) from reaction of monochloramine: a new
      disinfection by-product.
AB  - Studies have been conducted specifically to investigate the hypothesis that N
      nitrosodimethylamine (NDMA) can be produced by reactions involving
      monochloramine. Experiments were conducted using dimethylamine (DMA) as a model
      precursor. NDMA was formed from the reaction between DMA and monochloramine
      indicating that it should be considered a potential disinfection by-product. The
      formation of NDMA increased with increased monochloramine concentration and
      showed maximum in yield when DMA was varied at fixed monochloramine
      concentrations. The mass spectra of the NDMA formed from DMA and 15N isotope
      labeled monochloramine (15NH2Cl) showed that the source of one of the nitrogen
      atoms in the nitroso group in NDMA was from monochloramine. Addition of 0.05 and
      0.5 mM of preformed monochloramine to a secondarily treated wastewater at pH 7.2
      also resulted in the formation of 3.6 and 111 ng/L of NDMA, respectively, showing
      that this is indeed an environmentally relevant NDMA formation pathway. The
      proposed NDMA formation mechanism consists of (i) the formation of 1,1
      dimethylhydrazine (UDMH) intermediate from the reaction of DMA with
      monochloramine followed by, (ii) the oxidation of UDMH by monochloramine to NDMA,
      and (iii) the reversible chlorine transfer reaction between monochloramine and
      DMA which is parallel to (i). We conclude that reactions involving monochloramine
      in addition to classical nitrosation reactions are potentially important pathways
      for NDMA formation.

PMID- 11848352
TI  - The use of hydrous iron (III) oxides for the removal of hydrogen sulphide in
      aqueous systems.
AB  - The potential for iron (hydr)oxides to remove dissolved hydrogen sulphide from
      seawater has been examined under flow-through conditions. Ferrihydrite (a hydrous
      iron (III) oxide) was stabilised by precipitation onto zeolite pellets, and rates
      of sulphide removal were determined under laboratory conditions at pH 8.5.
      Sulphide removal kinetics were dependent on the initial sulphide concentration,
      substrate mass and flow rate. The experimental data suggest that these parameters
      can be optimised to result in the rapid and effective removal of hydrogen
      sulphide. The results from laboratory experiments compared favourably with
      sulphide removal kinetics determined in a series of experiments performed online
      in a recirculating mariculture production system. However, the presence in
      solution of ligands such as phosphate may also significantly affect reaction
      rates; a 50% reduction in sulphide removal rate for substrate removed from an
      online system was partly attributed to phosphate adsorption. The formation of a
      more crystalline, less reactive iron (hydr)oxide in recharged substrate was the
      likely result of FeS oxidation, which may also have contributed to the observed
      reduction in sulphide removal rates. Ferrihydrite-coated zeolite would appear to
      provide an efficient, low-cost method for sulphide removal, which is particularly
      suited to relatively small-scale aqueous flow-through systems. The reaction of
      iron (hydr)oxides with dissolved sulphide is also accompanied by a distinct
      colour change due to the formation of black FeS(s) which, under appropriate
      conditions, may be used as a rapid indicator of sulphidic conditions.

PMID- 11848353
TI  - The significance of entry routes as point and non-point sources of pesticides in
      small streams.
AB  - In an agricultural catchment area in Germany we analyzed water samples from five
      entry routes for 2 insecticides. 5 fungicides and 13 herbicides. The sewage plant
      outlet and the emergency overflow of a sewage sewer contained only herbicides. In
      each farmyard runoff we found on average 24 g pesticides during application
      period, presumably caused by cleaning the spraying equipment. In comparison, the
      field runoff and the rainwater sewer contained less load, but also insecticides,
      fungicides and herbicides. The sewage plant caused 65.9% of the total herbicide
      load, the sewage sewer 19.8% and the farmyard runoff 12.8%. The farmyards also
      caused 83.7% of total insecticide and 83.8% of fungicide load. The total load of
      all entry routes is correlated with the amount of pesticides applied in the
      catchment area and the Ko/w value for each pesticide (mult. regress. r2: 0.82;
      p<0.0001; n = 14). In stream A the sewage plant caused a slight but continuous
      contamination by herbicides with 82% of the total load found during low-water
      phases. In comparison, stream B had only farmyard runoff and non-point sources,
      which caused high peaks of herbicide and a contamination by insecticides.
      Consequently, high-water phases generated 70% of the total pesticide load.

PMID- 11848354
TI  - Modeling the sequential photodechlorination of hexachlorobenzene in surfactant
      micelles.
AB  - A five-stage consecutive irreversible model is derived to predict the
      photodegradation of hexachlorobenzene (HCB) in a surfactant solution, which was
      proven to be a useful treatment process following the surfactant-aided soil
      washing or remediation. The photodegradation of HCB in surfactant micelles is
      dominated by photodechlorination, which sequentially removes chlorides one at a
      time. The minor pathways of photoisomerization and photochlorination were
      neglected in the kinetic model. The results show that the derived consecutive
      irreversible model can accurately predict the decay of HCB and the formation (and
      decay) of its less-chlorinated congeners. The initial rate approach was used to
      identify the proper range of decay rate of each chlorinated benzene; so the
      overall rate constants can be determined easier by trial. The decreased
      performance of a completely mixed flow reactor (CMFR) with continuous input is
      also quantified compared to a batch reactor.

PMID- 11848355
TI  - Elimination of cadmium trace contaminations from drinking water.
AB  - Raw waters polluted with trace heavy metals present serious problems to the part
      of the Chinese water supply. One of the important contaminants is cadmium.
      Removal of trace amounts of heavy metals can be achieved by means of selective
      sorption processes. One of the possibilities is the application of weak base
      anion exchangers. LEWIS-base/acid interactions lead to an exclusive sorption of
      heavy metal cations and an equivalent amount of anions of strong acids. The
      respective elimination of cadmium from pure solutions and spiked natural water
      and the regeneration of the exhausted exchanger has been investigated. The
      results demonstrate a very efficient elimination. The standards for drinking
      water are met for a very large relative volume of treated water. In addition,
      even a considerable share of dissolved organic matter is adsorbed. Regeneration
      requires a first step with sulfuric acid to remove the metals and a second one
      with sodium hydroxide to neutralize the exchanger and to displace the DOC
      adsorbed. The heavy metals can be concentrated in a small volume which
      facilitates the discharge of the waste.

PMID- 11848356
TI  - Characterization of dissolved organic matter in effluents from wastewater
      treatment plants.
AB  - Dissolved organic matter (DOM) in effluents from sewage and human-wastes
      treatment plants (STPEs and HWTPEs) was fractionated using resin adsorbents into
      six classes: aquatic humic substances (AHS), hydrophobic bases (HoB), hydrophobic
      neutrals (HoN), hydrophilic acids (HiA), hydrophilic bases (HiB), and hydrophilic
      neutrals (HiN). DOM-fraction distribution varied substantially depending on the
      kind of wastewater and the type of treatment process. AHS and HiA dominated in
      all effluents, collectively accounting for more than 55% of the DOM measured as
      dissolved organic carbon (DOC). In particular, HiA were the most abundant
      fraction in the effluents, constituting 32-74% of the DOM. AHS appeared to be the
      second most dominant fraction and varied considerably, accounting for 3-28% of
      the DOM. The HoN fraction also varied from 0-21%. AHS, HoN, and HiA were the
      fractions that changed substantially and differed characteristically among the
      samples studied. The ratios of ultraviolet absorbance to DOC (UV: DOC ratio) in
      all effluents exhibited a common relationship: AHS> total DOM > HiA.
      Nevertheless, the ratios were substantially different between STPEs and HWTPEs
      and among HWTPEs. For HWTPEs, the effluent from the chemical coagulation process
      had the highest UV: DOC ratios. On the other hand, the effluent from the
      ultrafiltration and activated carbon adsorption processes had the lowest ratios.
      Molecular size distribution of the effluents was determined by size exclusion
      chromatography and found to exhibit a relatively narrow size range and low weight
      averaged molecular weights ranging from 380 to 830 g mol(-1). The weight-averaged
      molecular weight of DOM increased as the UV: DOC ratio of total DOM increased.

PMID- 11848357
TI  - Effectiveness and mechanism of potassium ferrate(VI) preoxidation for algae
      removal by coagulation.
AB  - Jar tests were conducted to evaluate the effectiveness of potassium ferrate
      preoxidation on algae removal by coagulation. Laboratory studies demonstrated
      that pretreatment with potassium ferrate obviously enhanced the algae removal by
      coagulation with alum [Al2(SO4)3 . 18H2O]. Algae removal efficiency increased
      remarkably when the water was pretreated with ferrate. A very short time of
      preoxidation was enough to achieve substantial algae removal efficiency, and the
      effectiveness was further increased at a prolonged pretreatment time.
      Pretreatment with ferrate resulted in a reduction of alum dosage required to
      cause an efficient coagulation for algae removal. The obvious impact of cell
      architecture by potassium ferrate was found through scanning electron microscopy.
      Upon oxidation with ferrate. the cells were inactivated and some intracellular
      and extracelluar components were released into the water, which may be helpful to
      the coagulation by their bridging effect. Efficient removal of algae by potassium
      ferrate preoxidation is believed to be a consequence of several process
      mechanisms. Ferrate preoxidation inactivated algae, induced the formation of
      coagulant aid, which are the cellular components secreted by algal cells. The
      coagulation was also improved by increasing particle concentration in water,
      because of the formation of the intermediate forms of precipitant iron species
      during preoxidation. In addition, it was also observed that ferrate preoxidation
      caused algae agglomerate formation before the addition of coagulant, the
      subsequent application of alum resulted in further coagulation.

PMID- 11848358
TI  - Experimental study and modelling of lead solubility as a function of pH in
      mixtures of ground waters and cement waters.
AB  - The purpose of this study was the simulation of lead solubility equilibria in
      mixtures of concrete lixiviation waters and ground waters in order to obtain the
      data necessary for the modelling of lead behaviour. The lixiviation water was
      impossible to obtain in sufficient quantity by compression of concrete specimens
      and was replaced by cement water prepared by mixing a CLC or CPA cement
      suspension in distilled water under argon. Three lead salts, PbCl2, PbSO4 and
      PbCO3, were studied; they correspond to the anions found most frequently in the
      ground waters. The experimental curves of lead solubility were determined, at 20
      degrees C, from pH 5 to 13, for various systems: cement water/lead salt/ground
      water. The modelling of 10 systems was carried out by the PHREEQC code from the
      solution compositions (ground water and cement water mixtures) and the
      thermodynamic constants obtained from the MINTEQ data base. The chemical models
      included the nature of the species in solution and the solid phases in
      equilibrium together with the corresponding values for the logarithms of the
      formation constants or solubility products. These models were validated by
      comparing the experimental pH and solubilised lead concentration values with the
      values calculated using the PHREEQC code.

PMID- 11848359
TI  - Investigation of assimilable organic carbon (AOC) and bacterial regrowth in
      drinking water distribution system.
AB  - This paper investigated the variation of assimilable organic carbon (AOC)
      concentrations in water from several typical water treatment plants and
      distribution systems in a northern city of China. It is concluded from this study
      that: (1) The AOC in most of the product water of the studied water treatment
      plants and the water from the associated distribution systems could not meet the
      biostability criteria of 50-100 microg/L. (2) Only 4% of the measured AOC
      concentrations were less than 100 microg/L. However, about half of the measured
      AOC values were less than 200 microg/L. (3) Better source water quality resulted
      in lower AOC concentrations. (4) The variation of AOC concentrations in
      distribution systems was affected by chlorine oxidation and bacterial activity:
      the former resulted in an increase of AOC value while the latter led to a
      reduction in AOC. (5) The variation of AOC concentration followed different
      patterns in different distribution systems or different seasons due to their
      respective operational characteristics. (6) Less than 30% of AOC could be removed
      by a conventional treatment process, whereas 30-60% with a maximum of 50-60%
      could be removed by granular activated carbon (GAC). (7) The observation via
      scanning electron microscope (SEM) on distribution pipe tubercle samples
      demonstrated that the pipe inner wall was not smooth and bacteria multiplied in
      the crevice as well as in the interior wall of distribution pipes.

PMID- 11848360
TI  - Removal of exhausted oils by adsorption on mixed Ca and Mg oxides.
AB  - Adsorption tests were performed on two different exhausted oils to reduce their
      polluting and health hazard potential: a "water-insoluble oil", utilised for
      automotive engine lubrication, and an "emulsified" oil, used as coolant for metal
      cutting tools. Dolomite, a low-cost recovery material, was used to prepare two
      effective adsorbents: (a) a mixed Ca and Mg oxide obtained by thermal
      decomposition of dolomite at 1800 degrees C, and (b) an activated material
      obtained by submitting this product to chemical treatment with HCl. Preliminary
      tests carried out with an excess of the former material showed that the insoluble
      oil was adsorbed with lower yield (Y = 0.40) than the soluble (emulsified) oil (Y
      = 0.60). The material activation with HCl remarkably improved the adsorption of
      soluble oil organic fraction (Y > 0.90), while only a little increase in the
      removal yield was observed for the insoluble oil (Y = 0.44). The results
      presented and discussed in this work pointed out that the products of dolomite
      calcination can successfully replace the conventional adsorbing materials in the
      removal of organic pollutants, with particular concern to exhausted soluble oils,
      which cannot usually be recycled, thus reducing the operational costs of their
      treatment.

PMID- 11848361
TI  - Organotin contamination in sediments from the Western Mediterranean enclosures
      following 10 years of TBT regulation.
AB  - Organotin (OT) compounds, namely butyl and phenyl, were measured in 38 recent
      sediments collected in harbours of the Western Mediterranean Sea (Northern: 4 and
      Southern: 9) and domestic and industrial sewage disposal sites (Northern: 9 and
      Southern: 1). Butyltins were the predominant tin species identified as being
      tributyltin (TBT) widespread in the whole area which suggests recent inputs of
      OTs. The highest levels of TBT were detected in commercial harbours associated
      with inputs from large vessels (average value: 5.0 microg TBT g(-1). Moreover,
      relatively high TBT values were also detected in fishing and recreational boating
      areas (average level ca. 1.0 microg TBTg(-1)). Phenyltin derivatives occurred at
      lower levels than butyltins being the monophenyltin the predominant compound
      (average values 45-945 ng g(-1)). The large predominance of the phenyltin
      degradation products (i.e. mono and diphenyltin) over the parent compound (i.e.
      triphenyltin) suggests that there are almost no recent inputs of these compounds.
      Furthermore, a comparative study of the OT occurrence in the sewage sludge
      disposal sites offshore Barcelona and Almeria (domestic) and into the Tarragona
      harbour (industrial) shows that domestic primary sewage sludge effluents can
      contribute to coastal OT pollution (244ng TBT g(-1)). Nevertheless, sewage sludge
      is a secondary source of OT contamination in the coastal environment in
      comparison to commercial harbours. In a comparative study with previous data
      collected in the late 1980s, the present study reveals that OT regulations
      established in the Mediterranean region in 1991 on the use of TBT-based
      antifouling paints have been effective in marinas, but reveals a significant TBT
      contamination in commercial and fishing harbours.

PMID- 11848362
TI  - Evaluation of wastewater toxicity: comparative study between Microtox and
      activated sludge oxygen uptake inhibition.
AB  - Microtox is a frequent toxicity tool for the screening of wastewaters discharged
      into wastewater treatment plants. There is currently an increasing controversy
      between this test and others using activated sludge. A Microtox and electrolytic
      respirometry comparative study for toxicity determination has been performed.
      Seven organic and five inorganic toxic compounds have been assessed for comparing
      both methods. Microtox proved to have a higher sensitivity to toxicants but was
      less representative of effects on activated sludge compared to respirometry. For
      instance, assays accomplished with LAS, a biodegradable reference surfactant,
      showed a toxic effect by Microtox but good biodegradability and no toxicity in
      respirometry. This could be explained by the different nature of the biological
      material used, as Microtox utilises the seawater Vibrio fischeri, whereas
      respirometry uses the bacterial consortium in activated sludge. For the
      evaluation of the potential toxicity of a compound on a WWTP, the preferred
      biological material be used should be activated sludge itself. Results obtained
      with any other biological material would be just an approach to reality.

PMID- 11848363
TI  - The molecular size of natural organic matter (NOM) determined by diffusivimetry
      and seven other methods.
AB  - The objectives of this work are to (1) determine the diffusion coefficients of
      natural organic matter (NOM) by diffusivimetry, (2) compare the results with
      diffusion coefficients determined by two other methods (fluorescence correlation
      spectroscopy (FCS) and dynamic adsorption experiments (DAM), (3) compare
      molecular weights derived from the diffusion coefficients to molecular weights
      determined by three different ultrafiltration experiments and high perfomance
      size exclusion chromatography (HPSEC). The diffusion coefficients determined in
      this work (stirred diffusion cell) are about 70% higher than that determined by
      DAM, and agree well with diffusion coefficients determined by FCS. Molecular
      weights determined by HPSEC are of the same magnitude as molecular weights
      derived from diffusion coefficients. Molecular weights determined by
      ultrafiltration vary considerably depending on the choice of membrane types.
      Membranes made of cellulose acetate generate results similar to results derived
      from diffusion coefficients. Membranes made of regenerated cellulose and
      polyether sulfone appear to retain too much of NOM, resulting in artificially
      high molecular weights.

PMID- 11848364
TI  - The effect of polymer addition on granulation in an anaerobic baffled reactor
      (ABR). Part I: process performance.
AB  - The stability and performance of an anaerobic baffled reactor (ABR) treating an
      ice-cream wastewater at several organic loading rates have been investigated.
      Specifically, it was determined whether an ABR would promote phase separation and
      if a polymer additive was capable of enhancing granule formation in an ABR. In
      order to achieve these goals, two ABRs, having identical dimensions and
      configurations, were used to study the above objectives using a synthetic ice
      cream wastewater. The ABR proved to be an efficient reactor configuration for the
      treatment of a high-strength synthetic ice-cream wastewater. An organic loading
      rate of around 15 kg CODm(-3) d(-1) was treated with a 99% COD removal
      efficiency. From the jar test and inhibition assay, it was concluded that Kymene
      SLX-2 was the most effective and least inhibitory polymer tested. The methane
      yield was higher in the polymer-amended reactor compared to the control reactor.
      In addition, polymer addition resulted in a considerably higher degree of biomass
      retention and lower solids washout from the ABR. Consequently, it demonstrated
      that there was a considerable potential for sludge conditioning in ABRs by
      facilitating better biomass retention within the reactor which in turn led to
      better process performance. Granulation was achieved in both ABRs within 3
      months. However, the granules from the polymer-amended reactor appeared earlier
      and were generally larger and more compact, although this was not quantified in
      detail during the present study. The main advantage of using an ABR comes from
      its compartmentalised structure. The first compartment of an ABR may act as a
      buffer zone to all toxic and inhibitory material in the feed thus allowing the
      later compartments to be loaded with a relatively harmless, balanced and mostly
      acidified influent. In this respect, the latter compartments would be more likely
      to support active populations of the relatively sensitive methanogenic bacteria
      and partly explains why the best granules and the highest methane yield were
      obtained in Compartment 2. It is unlikely that a complete separation of phases
      (acidogenic and methanogenic) occurred within the ABRs since methane production
      was observed in all compartments, although this was low (approximately 40% of all
      gas composition) in Compartment 1, becoming higher (approximately 70%) in the
      following compartments.

PMID- 11848365
TI  - The effect of polymer addition on granulation in an anaerobic baffled reactor
      (ABR). Part II: compartmentalization of bacterial populations.
AB  - The microbial ecology of wastewater treatment plants remains one of the least
      understood aspects in both aerobic and anaerobic systems, despite the fact that
      both processes are ultimately dependent on an active biomass for operational
      efficiency. Ultimately, future developments in anaerobic treatment processes will
      require a much greater understanding of the fundamental relationships between
      bacterial populations within the biomass if optimum process efficiency is to be
      fully realised. This study assesses the influence of polymer addition on granule
      formation within an ABR and compares the ecology of the biomass in each
      compartment of two ABRs treating ice-cream wastewater. To our knowledge, this is
      the first reported characterisation of the microbiology of acidogenic and
      methanogenic bacteria in the individual compartments of an ABR. The polymer
      amended reactor contained sludge that had a greater density of anaerobic bacteria
      and larger and denser granules than the control reactor, indicating that polymer
      addition possibly contributed to the retention of active biomass within the ABR.
      The average fraction of autofluorescent methanogens was lower, with 1.5% being in
      the initial compartments of the ABRs, compared to the last compartment which had
      15%, showing that each compartment of an ABR had a unique microbial composition.
      Partial spatial separation of anaerobic bacteria appeared to have taken place
      with acidogenic bacteria predominating in the initial compartments and
      methanogenic bacteria predominating in the final compartments. Scanning electron
      micrographs have revealed that the dominant bacteria in the initial compartments
      of the ABR (Compartments 1 and 2) were those which could consume H2/CO2 and
      formate as substrate, i.e. Methanobrevibacter, Methanococcus, with populations
      shifting to acetate utilisers, i.e. Methanosaeta, Methanosarcina, in the final
      compartments (Compartments 3 and 4). In addition, there appeared to be a
      stratified structure to the bacterial genera present within the granules.

PMID- 11848367
TI  - The effect of UV irradiation on human-derived Giardia lamblia cysts.
AB  - The effect of UV irradiation on human-derived Giardia lamblia cysts (WB isolate,
      cultivated using the gerbil model, and purified to homogeneity) was assessed
      using a 254nm collimated beam protocol. The infection kinetics of UV-exposed
      cysts were directly compared to the infection kinetics of control (non-UV
      exposed) cysts. This demonstrated that a UV dose at 254 nm resulted in
      significant inactivation of the Giardia cysts. Up to 2 log (99%) inactivation was
      observed at a UV dose of approximately 10 mJ cm(-2) (range 9.3-11.7 mJ cm(-2)).
      Higher UV doses (between 20 and 40 mJ cm(-2)) resulted in up to 3 log (99.9%)
      inactivation of the cysts. The actual inactivation at these dose levels could be
      higher, but for this study the maximum quantifiable limit of cyst inactivation
      was up to 3 logs (99.9%). Chemical actinometry using the Rahn potassium iodide
      actinometer was used to confirm the UV dose delivered. No correlation between a
      PI/DAPI vital dye viability assay and the infectious dose assay was observed. The
      vital dye viability assay demonstrated no inactivation. Future work using an
      alternative UV delivery systems including a demonstration-scale device is
      recommended and more work with a variety of isolates is warranted.

PMID- 11848366
TI  - Germanium-68 as a tracer for silicon fluxes in freshwater sediment.
AB  - The sorption of Si may decisively influence the P dynamics in surface sediment
      through competitive ligand exchange mechanisms. Many aspects of the process, such
      as the impact of Si dissolving from diatoms, are both insufficiently known and
      difficult to monitor by quantitative analyses due to the ubiquitousness of Si in
      sediment. Since the radioactive isotopes of Si have impractical half-times, the
      applicability of 68Ge as a tracer for Si additions in both inorganic and biogenic
      form to freshwater sediment (Lake Vesijarvi, Southern Finland) was studied in a
      24-h laboratory experiment. The 68Ge-label was added to the sediment with either
      inorganic Si (940mg l(-1)) or diatoms (3.2 x 10(6) cellsl(-1)), and the
      distributions of the 68Ge-label and the different forms of added Si between the
      interstitial water and sequentially extracted, solid-phase sediment pools were
      critically examined. The inorganic Si addition significantly increased the amount
      of Si in the interstitial water and in the reversibly bound fraction, while the
      diatom addition had no discernible effects. The relative distribution of Si and
      68Ge between the various sediment pools indicated that the first sorption phase
      of the added inorganic Si was similar to that reported for P. The high
      concentration of diatom-derived 68Ge-labelled Si in the interstitial water and in
      the easily soluble, reversibly bound pool indicated rapid dissolution of the
      added diatoms. The comparable distributions of the diatom-derived and inorganic
      Si-derived 68Ge-label within the studied pools indicated that the sorption of Si
      dissolving from diatoms in surface sediment closely resembles that of an
      inorganic addition of Si. Caution about the chemical speciation of the 68Ge-label
      is, however, advisable in sediment environments. Fractionation procedures
      designed for e.g. P may also be of limited use when applied to a different
      element, such as Si.

PMID- 11848368
TI  - Some problems in the detection of strong mutagen MX formed by chlorinating the
      aromatic acids and phenolic compounds.
AB  - Ten compounds with aromatic acid and phenolic structure were chlorinated at
      laboratory conditions and MX analysis by GC/MS at scan mode. None of these
      compounds produced MX, which is contrary to the results of other researchers. The
      whole procedure was investigated and it was found that the results obtained at
      scan mode was more reliable than at SIM mode because of the possible
      interference. The structural characteristic of the precursors of MX is proposed.

PMID- 11848369
TI  - Hydrolysis of 4-methylumbelliferyl-beta-D-glucuronide in differing sample
      fractions of river waters and its implication for the detection of fecal
      pollution.
AB  - The hydrolysis rate of 4-methylumbelliferyl-beta-D-glucuronide (MUG-HR) was
      determined in unamended samples, filtered samples, and in corresponding buffer
      resuspended filter residues of various river waters of slight to excessive fecal
      pollution covering a four orders of magnitude range. Regression analysis of the
      log MUG-HR of the unamended water samples versus the log MUG-HR of the filter
      residues revealed a highly significant linear relationship (R2 = 0.94; p<0.001).
      The median of the MUG-HR of the filtrated water samples was about 10% the MUG-HR
      of the corresponding unamended water samples. If MUG-HR determinations were used
      as a surrogate for estimating fecal coliform contamination, both the MUG-HR of
      the unamended water samples and the MUG-HR of the filter residues would have been
      equally adequate techniques at river sites of higher fecal pollution levels.
      However, at river locations of decreased fecal pollution, MUG-HR determination of
      filter residues appeared to be the more sensitive technique in order to estimate
      fecal coliform concentrations.

PMID- 11848370
TI  - Degradation of polyethoxylated nonylphenols in a sewage treatment plant.
      Quantitative analysis by isotopic dilution-HRGC/MS.
AB  - Polyethoxylated alkylphenols (APnEO, where n is the number of ethylene oxide
      molecules), are non-ionic surfactants widely used for domestic and industrial
      purposes. Most of APnEO are polyethoxylated nonylphenols (NPnEO). NPnEO are
      widespread environmental pollutants with relatively low toxicity for mammals and
      higher toxicity for aquatic organisms. In addition, they have been described as
      endocrine disrupters in recent publications. One of the main problems related to
      these surfactants is their uncomplete degradation, even in the most effective
      sewage treatment plants. Usually, the final products, more toxic and resistant to
      biological degradation than NPnEO, are nonylphenol (NP), monoethoxylated
      nonylphenol (NP1EO), diethoxylated nonylphenol (NP2EO), nonylphenoxy acetic acid
      (NP1EC), and nonylphenoxyethoxy acetic acid (NP2EC). In this paper, the
      degradation of NPnEO was studied in the different processes of a sewage treatment
      plant. For this purpose, NP, NP1EO and NP2EO were analysed in composite samples
      collected at different points along the plant (influent, pre-treatment effluent,
      primary effluent, plant effluent). Analyses were carried out by isotopic dilution
      HRGC/MS, using available labelled nonylphenols (13C6-NP, 13C6-NP1EO, 13C6-NP2EO)
      as internal standards. Extraction of NPnEO from aqueous samples, previous to
      analysis, was performed by the Likens-Nickerson method (simultaneous steam
      distillation/solvent extraction, SDE).

PMID- 11848371
TI  - Contributions of genotoxic precursors from tributary rivers and sewage effluents
      to the Yodo River in Japan.
AB  - The cause of water pollution in the Yodo River was examined regarding the
      mutagenic potentials formed by chlorination of river waters and sewage effluents
      along the river. Mutagenicity of the extracts from chlorinated waters was
      measured by Ames test using S. typhimurium TA100 strain without metabolic
      activation. Mutagenic formation potentials of sewage effluents were 4-5 times
      higher than those of the three tributary river waters, the Kizu, Uji and Katsura
      Rivers. The contribution rates of the pollution loads from the three river waters
      and total of four sewage effluents to the Yodo River were revealed to be 10.2%,
      42.2%, 22.1% and 25.5%, respectively. The rate of the sewage effluents occupied
      one-fourth and exceeded the rates of the Kizu and Katsura Rivers. The
      contribution rate of the two sewage effluents to the Katsura River was 46.3%. It
      could be confirmed that the relationship between COD and MFP in river waters and
      sewage effluents was very high with a correlation coefficient. These results
      indicated that the waters inflowing to the Yodo River were contaminated with
      numerous organic compounds, and the sewage effluents especially contribute to the
      formation of genotoxicity by the interaction between chlorine and organic
      components as genotoxic precursors in the purification plants.

PMID- 11848372
TI  - A simple biofilm model of bacterial competition for attached surface.
AB  - A simple biofilm model of competition in bacterial growth for an attached surface
      is developed. Competition for the attached surface is expressed with the crowded
      and detachment effects. The developed model is verified by comparing simulated
      results with data obtained in the experiments of batch culture of nitrifier and
      continuous treatment of actual sewage with biofilm reactor. This model can
      favorably simulate the growth competition between autotrophic and heterotrophic
      bacteria for the attached surface. Then some parameters for nitrification process
      are discussed with this model. It is clarified that the effective removal of
      organic matter before nitrification tank is required for effective nitrification
      in the biofilm reactor.

PMID- 11848373
TI  - Effects of SO2 and NO on growth of Chlorella sp. KR-1.
AB  - Effects of the toxic compounds in flue gas, SOx and NOx, on growth of Chlorella
      sp. KR-1 have been determined. Although growth of KR-1 was suppressed by the
      toxic compounds, KR-1 exhibited excellent tolerances to SOx compared to other
      algal strains. When Chlorella KR-1 was cultured with the model gas containing 60
      ppm SO2, the linear growth rate was 1.24 g/l day which is about 25% lower than
      that of the control culture aerated with the gas mixture containing no toxic
      compounds, SO2 and NO. KR-1 could grow even with the model gas containing 100 ppm
      SO2 and the linear growth rate of KR-1 in the culture was 0.78 g/l day. The
      period for lag phase was increased with increasing of SO2 concentration that also
      resulted in the decrease of the linear growth rate and the maximum cell
      concentration. Direct CO2 fixation by Chlorella KR-1 has been successfully done
      using actual flue gases from a liquified natural gas (LNG)- or diesel-fueled
      boiler. These results indicated that Chlorella KR-1 may be applied for direct CO2
      fixation from actual flue gas.

PMID- 11848374
TI  - Characterization of degradation products from alkaline wet oxidation of wheat
      straw.
AB  - Alkaline wet oxidation pre-treatment (water, sodium carbonate, oxygen, high
      temperature and pressure) of wheat straw was performed as a 2(4-1) fractional
      factorial design with the process parameters: temperature, reaction time, sodium
      carbonate and oxygen. Alkaline wet oxidation was an efficient pre-treatment of
      wheat straw that resulted in solid fractions with high cellulose recovery (96%)
      and high enzymatic convertibility to glucose (67%). Carbonate and temperature
      were the most important factors for fractionation of wheat straw by wet
      oxidation. Optimal conditions were 10 min at 195 degrees C with addition of 12
      bar oxygen and 6.5 g l(-1) Na2CO3. At these conditions the hemicellulose fraction
      from 100 g straw consisted of soluble hemicellulose (16 g), low molecular weight
      carboxylic acids (11 g), monomeric phenols (0.48 g) and 2-furoic acid (0.01 g).
      Formic acid and acetic acid constituted the majority of degradation products (8.5
      g). The main phenol monomers were 4-hydroxybenzaldehyde, vanillin,
      syringaldehyde. acetosyringone (4-hydroxy-3,5-dimethoxy-acetophenone), vanillic
      acid and syringic acid, occurring in 0.04-0.12 g per 100 g straw concentrations.
      High lignin removal from the solid fraction (62%) did not provide a corresponding
      increase in the phenol monomer content but was correlated to high carboxylic acid
      concentrations. The degradation products in the hemicellulose fractions co-varied
      with the pre-treatment conditions in the principal component analysis according
      to their chemical structure, e.g. diacids (oxalic and succinic acids), furan
      aldehydes, phenol aldehydes, phenol ketones and phenol acids. Aromatic aldehyde
      formation was correlated to severe conditions with high temperatures and low pH.
      Apart from CO2 and water, carboxylic acids were the main degradation products
      from hemicellulose and lignin.

PMID- 11848375
TI  - Solid state fermentation of broiler litter for production of biocontrol agents.
AB  - Several varieties of heat-sterilized broiler litter with 60% (wet basis, wb)
      moisture content were substrate in solid-state fermentations to produce
      biocontrol agents. Litter varieties included litter produced by one flock of
      broilers from medicated and non-medicated controlled rations, and litter produced
      by two flocks and four flocks on a single application of bedding material from
      medicated commercial sources. Litter preparations were inoculated with
      monocultures of Bacillus thuringiensis serovar japonensis strain Buibui, a
      pathogen of Japanese beetle larvae (Popillia japonica), or Pseudomonas
      fluorescens 2-79. B. thuringiensis did not grow in unextracted 1-flock litter nor
      in water extracted litter, but grew in methanol extracted litter to 5 x 10(10)
      cell forming units (CFU)/g litter (dry weight, dw) and a spore count of 1 x
      10(10) CFU/g litter (dw). B. thuringiensis also grew in unprocessed 2-flock and 4
      flock litter, achieving cell counts of 3 x 10(9) and 1 x 10(9) CFU/g litter (dw),
      respectively, and spore counts of 1 x 10(9) CFU/g litter (dw). P. fluorescens
      grew in medicated 1-flock litter with no extraction to a cell density greater
      than 4 x 10(11) CFU/g litter (dw). Bioassays in soil containing over 0.5% (db)
      litter fermented with B. thuringiensis resulted in over 90% mortality in 21 days
      for first instars of Japanese beetle when compared to a control treatment using
      compost without fermented litter. The investigations demonstrate that bacterial
      biocontrol agents produced via solid substrate fermentations using broiler
      poultry litter have potential in biocontrol applications in the soil environment.

PMID- 11848376
TI  - Lipid production by Yarrowia lipolytica growing on industrial glycerol in a
      single-stage continuous culture.
AB  - Yarrowia lipolytica LGAM S(7)1 presented remarkable growth on industrial glycerol
      used as sole carbon substrate. Nitrogen-limited flask cultures were accompanied
      by restricted synthesis of reserve lipid, whilst amounts of citric acid were
      produced extracellularly. On the contrary, high amounts of reserve lipid (up to
      3.5 g/l, 43% w/w of lipids in dry biomass) were produced in highly aerated
      continuous cultures. Lipid production was favoured at low specific dilution rates
      whilst fat-free material yield increased over the whole range of D (h(-1)). The
      maximum volumetric productivity obtained was 0.12 g lipid/1 h. Storage lipid
      composition did not present remarkable changes in the specific dilution rates
      tested. Oleate and linoleate were the dominant cellular fatty acids.

PMID- 11848377
TI  - Energy evaluation of forest residues originated from Eucalyptus globulus Labill
      in Galicia.
AB  - The possibility of retrieving the energy contained in forest residues originating
      from wood exploitation in Galicia (Spain) is evaluated. This study was made on
      Eucalyptus globulus Labill occupying a forest surface of 240000 ha. This species
      plays an important role in the economical development of Galicia, as it is the
      main forest species for production of pulp. Sampling was made over 1999 in seven
      different zones, three main stations plus four selected for comparison, situated
      in Galicia. The residues originating from cutting were sorted into three
      different groups and their calorific values were measured by static bomb
      calorimetry. These calorific values, close to 7200 kJ kg(-1), make possible the
      use of this residual biomass as an energy source. Calorific values were measured
      by static bomb calorimeter in an oxygen atmosphere. Flammability was determined
      using a standard epiradiator. Simultaneously, some other parameters, elementary
      chemical composition, heavy metal contents, moisture, density, ash percentage
      after combustion in the bomb, and main bioclimatic characteristics, were also
      determined.

PMID- 11848378
TI  - Production of carboxylic acids from hydrolyzed corn meal by immobilized cell
      fermentation in a fibrous-bed bioreactor.
AB  - Corn meal hydrolyzed with amylases was used as the carbon source for producing
      acetic, propionic, and butyric acids via anaerobic fermentations. In this study,
      corn meal, containing 75% (w/w) starch, 20% (w/w) fibers, and 1.5% (w/w) protein,
      was first hydrolyzed using amylases at 60 degrees C. The hydrolysis yielded
      approximately 100% recovery of starch converted to glucose and 17.9% recovery of
      protein. The resulting corn meal hydrolyzate was then used, after sterilization,
      for fermentation studies. A co-culture of Lactococcus lactis and Clostridium
      formicoaceticum was used to produce acetic acid from glucose. Propionibacterium
      acidipropionici was used for propionic acid fermentation, and Clostridium
      tyrobutylicum was used for butyric acid production. These cells were immobilized
      on a spirally wound fibrous matrix packed in a fibrous-bed bioreactor (FBB)
      developed for multi-phase biological reactions or fermentation. The bioreactor
      was connected to a stirred-tank fermentor that provided pH and temperature
      controls via medium circulation. The fermentation system was operated at the
      recycle batch mode. Temperature and pH were controlled at 37 degrees C and 7.6,
      respectively, for acetic acid fermentation, 32 degrees C and 6.0, respectively,
      for propionic acid fermentation, and 37 degrees C and 6.0, respectively, for
      butyric acid production. The fermentation demonstrated a yield of approximately
      100% and a volumetric productivity of approximately 1 g/(1 h) for acetic acid
      production. The propionic acid fermentation achieved an approximately 60% yield
      and a productivity of 2.12 g/(1 h), whereas the butyric acid fermentation
      obtained an approximately 50% yield and a productivity of 6.78 g/(1 h). These
      results were comparable to, or better than those fermentations using chemically
      defined media containing glucose as the substrate, suggesting that these
      carboxylic acids can be efficiently produced from direct fermentation of corn
      meal hydrolyzate. The corn fiber present as suspended solids in the corn meal
      hydrolyzate did not cause operating problem to the immobilized cell bioreactor as
      is usually encountered by conventional immobilized cell bioreactor systems. It is
      concluded that the FBB technology is suitable for producing value-added
      biochemicals directly from agricultural residues or commodities such as corn
      meal.

PMID- 11848379
TI  - Pigeon pea waste as a novel, inexpensive, substrate for production of a
      thermostable alkaline protease from thermoalkalophilic Bacillus sp. JB-99.
AB  - Thermoalkaliphilic Bacillus sp. JB-99 was grown in a 250 ml Erlenmeyer flask
      containing 50 ml medium containing (g/l) Pigeon pea waste 10; NaNO3, 5.0; K2HPO4,
      5.0; MgSO4 x 2H2O, 0.2 and Na2CO3, 10.0. Incubations were carried out at 50
      degrees C on a rotary incubator shaker for 15 h. A high level of extra cellular
      thermostable protease activity was observed after 24 h incubation. The optimum
      temperature and pH for activity were 70 degrees C and 11, respectively, so this
      enzyme showed stable activity at high temperature and under alkaline conditions.

PMID- 11848380
TI  - Effects of temperatures and organic loading rates on biomethanation of acidic
      petrochemical wastewater using an anaerobic upflow fixed-film reactor.
AB  - The effect of temperature and organic loading rate on the rate of methane
      production from acidic petrochemical wastewater without neutralization was
      investigated by continuously feeding an anaerobic upflow fixed-film reactor. The
      temperatures selected for the studies were 25, 37, 45 and 55 degrees C. Organic
      loading rate (OLR) for each temperature was varied from 3.6 to 21.7 kg COD m(-3)
      d(-1). Best performance with respect to COD and BOD reduction, total gas
      production and methane yield was obtained with the reactor operating at 37
      degrees C. OLR could be increased to a maximum of 21.7 kg COD m(-3) d(-1) with 90
      95% COD and BOD reduction and methane yield of 0.450 m3 kg(-1) COD d(-1) added.
      The reactor operating at 55 degrees C gave the highest methane yield of 0.666 m3
      kg(-1) COD d(-1) at an OLR of 6 kg COD m(-3) d(-1). This decreased to 0.110 m3
      kg(-1) COD d(-1) when the OLR was increased to 18.1 kg COD m(-3) d(-1). The
      reactor operating at 45 degrees C gave a maximum methane yield of 0.416 m3 kg(-1)
      COD d(-1) added at an OLR of 6 kg COD m(-3) d(-1). On further increasing the OLR
      to 9 kg COD m(-3) d(-1), COD reduction was 89%, however, methane yield decreased
      to 0.333 m3 kg(-1) COD d(-1) added. The highest methane yield of 0.333 m3 kg(-1)
      COD d(-1) added at an OLR of 6 kg COD m(-3) d(-1) was obtained with reactors
      operating at 25 degrees C. These studies indicate potential rates of methane
      production from acidic petrochemical wastewater under different temperatures.
      This provides a guideline for various kinetic analyses and economic evaluation of
      the potential feasibility of fermenting acidic wastewater to methane.

PMID- 11848381
TI  - Persistence of immobilised and total urease and phosphatase activities in a soil
      amended with organic wastes.
AB  - This paper reports on the persistence of total and immobilised enzyme activities
      (urease and phosphatase) in a soil amended with organic wastes containing high
      levels of total-urease and phosphatase activity. Fresh organic materials showed
      the highest values for both total-enzymatic activities. The addition of organic
      waste to soil increased both total-enzymatic activities in the soil, which, after
      360 days, showed values above those of the control. Immobilised enzymes were also
      higher in the fresh wastes than in the soil with compost, while the specific
      enzymatic activity levels (enzymatic activity per unit of carbon) were similar.
      The immobilised urease activity was greater in the amended soil than in the
      control. At the beginning of the incubation period, the immobilised urease
      activity was significantly higher in the soil amended with fresh organic wastes
      than with compost. However, this activity decreased with incubation, whilst the
      compost-immobilised urease activity increased with time. The effect of organic
      amendment on immobilised phosphatase activity was similar to that shown by
      immobilised urease but less pronounced. The persistence of both enzymes was
      significantly higher in the soil amended with compost than in that amended with
      fresh materials.

PMID- 11848382
TI  - Effect of natural rubber processing sludge on the degradation of crude oil
      hydrocarbons in soil.
AB  - Crude oil-polluted soil (five parts of weathered crude oil per 100 parts of soil;
      equivalent to 50,000 mg oil kg(-1) soil) samples were slurried in deionised water
      (300% of the water retention capacity of the soil) and treated with various
      amounts of natural-rubber processing sludge (nitrogen content 62.15 mg kg(-1) and
      phosphorus contents 8.75 mg kg(-1)) in a well-stirred, continuously-aerated tank
      at 29 degrees C. Changes in the total hydrocarbon content of the soil sample were
      determined, using a spectrophotometric technique, as a function of time. The
      extent of crude oil degradation was markedly higher (by up to 100%) in the sludge
      treated soil than in the untreated soil sample. The efficiency of biodegradation
      of the crude oil hydrocarbons using the slurry-phase technique was compared with
      that of solid-phase technique.

PMID- 11848383
TI  - Quality of paper boards from arecanut leaf sheath.
AB  - A study was carried on utilizing arecanut leaf sheath for making paper boards.
      Paper boards were made with various combinations of arecanut leaf sheath with
      waste paper, 1:1, 1:2, 1:3, 3:1, 2:1, control (100% areca leaf sheath) and the
      qualities of these paper boards were tested as per the Bureau of Indian Standards
      (IS: 1060 (part-I)-1966). The paper boards made with more arecanut sheath
      materials had more resistance to water absorption. The addition of paper
      increased the substance weight of the paper boards. The 2:1 and 3:1 combinations
      of arecanut leaf sheath and waste paper had best tear strength, tensile strength,
      bursting strength and water resistance with minimum substance weight.

PMID- 11848384
TI  - The wear of metal-on-metal total hip prostheses measured in a hip simulator.
AB  - New generation metal-on-metal prostheses have been introduced to try and overcome
      the problem of osteolysis often attributed to the wear particles of the
      polyethylene component of conventional metal-on-ultra-high molecular weight
      polyethylene (UHMWPE) joints. The wear rates of four metal-on-metal joints (two
      different clearances) were assessed along with that of a conventional metal-on
      UHMWPE joint. Friction measurements of the metal-on-metal joints were taken
      before and after the wear test and compared. Two distinct wear phases were
      discernible for all the metal-on-metal joints: an initial wear phase up to 0.5 x
      10(6) cycles and then a lower steady state wear phase. The steady state wear rate
      of the 22 microm radial clearance metal-on-metal joint was lower than that for
      the 40 microm radial clearance joint, although this difference was not found to
      be significant (p > 0.15). The wear rates for all the joints tested were
      consistent with other simulator studies. The friction factors produced by each
      joint were found to decrease significantly after wear testing (p < 0.05).

PMID- 11848385
TI  - Elastohydrodynamic lubrication analysis of metal-on-metal hip prostheses under
      steady state entraining motion.
AB  - The elastohydrodynamic lubrication problem of metal-on-metal hip joint
      replacements was considered in this study. A simple ball-in-socket configuration
      was used to represent the hip prosthesis. The Reynolds equation in a spherical
      coordinate was adopted for the fluid-film lubrication analysis, to account for
      the ball-in-socket geometry. The corresponding elastic deformation was calculated
      by means of the finite element method in order to consider the complex ball-in
      socket geometry as well as the backing materials underneath the acetabular cup.
      Both the Reynolds and the elasticity equations were solved simultaneously using
      the Newton-Raphson finite difference method. The general methodology developed
      was then applied to a recent experimental prototype metal-on-metal hip implant.
      It was shown that the backing materials underneath the acetabular cup had little
      influence on the predicted contact pressure and the elastic deformation at the
      bearing surfaces for this particular example. Both the film thickness and the
      hydrodynamic pressure distributions were obtained under various loads up to 2500
      N. The predicted minimum lubricating film thickness from the present study was
      compared with a simple estimation using the Hamrock and Dowson formulae based
      upon an equivalent ball-on-plane model and excellent agreement was found.
      However, it was pointed out that for some forms of metal-on-metal hip prostheses
      with a thin acetabular cup, a polyethylene inlay underneath a metallic bearing
      insert or a taper connection between a bearing insert and a fixation shell, the
      general methodology developed in the present study should be used and this will
      be considered in future studies.

PMID- 11848386
TI  - Contact mechanics of a novel metal-on-metal total hip replacement.
AB  - The contact mechanics of a novel metal-on-metal total hip replacement (THR) were
      investigated in this study. The metal-on-metal prosthesis considered consists of
      a cobalt-chrome acetabular insert connected to a titanium shell through a taper
      contact, articulating against a cobalt-chrome femoral head. Both the experimental
      measurement of the displacement of the acetabular insert and the contact area
      between the two bearing surfaces, and the corresponding numerical predictions
      using the finite element method have been conducted. Excellent agreement has been
      demonstrated between the experimental measurement and the finite element
      prediction under various loads up to 3 kN. The maximum contact pressure at the
      articulating surfaces has been predicted to be about 31 MPa from a simple
      axisymmetric finite element model, significantly lower than that of a similar cup
      but with a monoblock construct. This has been mainly attributed to the
      flexibility of the insert, leading to an increase in the conformity between the
      femoral head and the acetabular insert. In addition, the predicted maximum
      contact pressure is only slightly increased to 37 MPa, from a more realistic
      three-dimensional anatomical finite element model. The design features on metal
      on-metal THRs have been shown to reduce contact stresses and may improve
      tribological performances of these hard-on-hard bearing couples.

PMID- 11848387
TI  - Long-term measurement of metacarpophalangeal joint motion in the normal and
      rheumatoid hand.
AB  - Low-profile flexible goniometers were used in an instrumented glove to monitor
      metacarpophalangeal (MCP) joint usage in patients with rheumatoid arthritis and
      control subjects over 3 days. Statistical analysis of the results provided
      descriptors of total joint motion per hour, the number of movements per hour and
      their duration, amplitude and angular velocity. The results show the patient
      group to have less overall joint usage than the control group, with movements
      being slower and smaller and with a restricted range. Yearly rates of joint usage
      were derived; these values are considerably higher than predicted in prosthetic
      joint testing protocols.

PMID- 11848388
TI  - Interface biomechanics of the Anca Dual fit hip stem: an in vitro experimental
      study.
AB  - The Anca Dual Fit hip stem (Cremascoli Wright, Milan, Italy) is a partially
      cemented stem developed to overcome the drawbacks of both cemented and uncemented
      fixations. Its design was based on the hypothesis that partial cementing would
      ensure the primary stability necessary to allow bone ingrowth on the cement-free
      stem surfaces. At the same time, the limitation of the cement to the proximal
      regions would prevent stress-shielding by increasing proximal load transfer.
      After finite element (FE) simulations and in vitro primary stability assessment,
      an analysis of the long-term stability of the Anca Dual Fit stem was necessary to
      conclude the preclinical testing. Three stems were implanted in composite femurs
      and subjected to testing for 1 x 10(6) cycles, each cycle reproducing the
      activity of stair climbing. The simulation was designed so as to replicate the
      physiological loading in a simplified, yet relevant way for this test. Various
      measurements were collected before, during and after the test in order to give
      exhaustive information on the response of the implant to long-term, cyclic
      loading. The present study confirmed the positive results of previous
      investigations, and proved that the Anca Dual Fit stem has excellent long-term
      stability; therefore successful clinical outcomes are predicted.

PMID- 11848389
TI  - Predictive rheological models for the consolidation behaviour of articular
      cartilage under static loading.
AB  - This paper evaluates an existing rheological model of articular cartilage and
      explores the representative capacity of other phenomenological models of the
      tissue's matrix within the framework of mechanical consolidation. A unique
      feature is the introduction of a swelling element in tandem with 'fluid-filled'
      hyperelastic rheological elements to predict the transient load-induced behaviour
      of the tissue and evaluate the role of swelling in determining its load-carriage
      mechanism. The rheological models proposed have been used to predict the
      dependence of the one-dimensional consolidation response of the articular
      cartilage matrix, and the results obtained have been compared with published
      experimental results. This comparison demonstrates that the hydrostatic excess
      pore pressure, especially in the initial stages of deformation cannot be
      predicted without an adequate representation of swelling and its non-linear
      interaction with mechanical governing parameters such as permeability and
      stiffness.

PMID- 11848390
TI  - Flow instabilities in a graft anastomosis: a study of the instantaneous velocity
      fields.
AB  - The major cause of arterial bypass graft failure is intimal hyperplasia.
      Fluctuating wall shear stresses in the graft, which are associated with disturbed
      flow, are believed to be important factors in the development and localization of
      intimal hyperplasia. This study, based upon water as the working fluid, has
      investigated the flow structure inside a 30 degree Y-junction with different
      fillet radii at the intersection between the graft and the host artery at various
      Reynolds numbers and distal outlet segment (DOS) to proximal outlet segment (POS)
      flow ratios. The structure of the flow has been investigated experimentally using
      particle image velocimetry (PIV). The two-dimensional instantaneous velocity
      fields confirm the existence of a very complex flow, especially in the toe and
      heel regions for the different fillet radii and clearly identify features such as
      sinks, sources, vortices and strong time dependency.

PMID- 11848391
TI  - An in vitro assessment of tissue compression damage during circular stapler
      approximation tests, measuring expulsion of intracellular fluid and force.
AB  - Circular staplers are among the many instruments used during minimally invasive
      or open surgery that should approximate soft tissue within safe compression
      limits. Previous in vivo suture-line blood flow measurement has suggested a safe
      thickness reduction limit of 25 per cent during circular stapling procedures. The
      present work investigates in vitro assessment of the maximum safe compression of
      large and small porcine intestines, measuring the required compressive force and
      the expelled intracellular fluid (measured as a potassium solution). A test-rig
      mounted on a materials testing machine allowed staplers of three sizes to
      compress tissue samples to thicknesses ranging from 90 to 45 per cent of original
      thickness. The expelled fluid was collected in 40 ml of 0.9 per cent NaCl and
      analysed in a flame photometer. The force measurements indicated that the small
      intestinal tissue samples underwent a sharp increase in stiffness over a strain
      range of 0.19-0.34. The large bowel tissue underwent a similar increase in
      stiffness over a planar compressive strain range of 0.19-0.40. The regularity of
      the potassium output results was limited, making it difficult to draw firm
      conclusions, although there was some indication that the potassium output from
      small intestinal tissue may change from erratic to approximately linear at a
      strain of approximately 0.19, while that of the large bowel tissue appeared to be
      approximately linear over the entire strain range tested. From the force
      measurements, it is concluded that strain-induced structural change may help
      provide a useful definition of safe tissue approximation. The possible
      implications for reduced dehiscence (wound disintegration) and stricture
      incidence in stapled anastomoses are discussed.

PMID- 11848392
TI  - An infant reciprocal walking orthosis: engineering development.
AB  - The growing trend of prescription of reciprocal walking orthoses for children
      under the age of 5 years has created a requirement for a new design of orthosis
      in this category. In response to this new demand, a prototype orthosis for
      infants, incorporating a specially developed hip joint and manufactured as a
      rehabilitation engineering device within the provisions of the EC Medical Devices
      Directive, has been produced and tested. A design feature that strongly
      influences the efficiency of walking is the rigidity of the body brace structure.
      Monitoring the specific structural performance of the body brace intended for
      infants showed that it would equal or improve the stiffness achieved in an
      orthosis for adults. Additionally its strength was comparable with the adult
      design, which has proven to be safe and reliable in many years of routine
      prescription. Incorporation of the infant body brace within a complete orthosis
      provided a structure of more acceptable physical dimensions for these more
      diminutive patients. The orthosis showed no incipient sign of failure after
      100,000 cycles of representative service loading equivalent to that imposed by a
      20 kg (5-year-old) patient. The results of structural assessment and cyclic load
      testing confirm that the design of the orthosis sufficiently satisfies the
      statutory requirements for devices that are safe and fit for purpose to permit
      field trials with patients.

PMID- 11848393
TI  - Importance of pin geometry on pin-on-plate wear testing of hard-on-hard bearing
      materials for artificial hip joints.
AB  - The contact mechanics between the pin and the plate used in simple wear screening
      tests were investigated in this study. Both soft-on-hard, such as ultra-high
      molecular weight polyethylene (UHMWPE)-on-metal or UHMWPE-on-ceramic, and hard-on
      hard, such as metal-on-metal, bearing couples were considered. The effect of the
      pin geometry and the misalignment between the pin and the plate were investigated
      on the predicted contact pressure distribution at the bearing surfaces using the
      finite element method. It was demonstrated that in the case of soft-on-hard
      bearing couples, neither the geometrical discontinuity of the pin surface nor the
      misalignment could cause a significant increase in the contact stress. However,
      for hard-on-hard combinations, even with a very small misalignment of 0.5 degrees
      between the pin and the plate, the geometrical discontinuity could lead to a more
      than tenfold increase in the predicted contact stress. This elevated contact
      stress may lead to a large scatter in the wear data and, even more importantly,
      structural damage of the bearing surfaces.

PMID- 11848394
TI  - Rapid localization of a gene within BACs and PACs.

PMID- 11848395
TI  - One-step RT-PCR for screening microdissected tissue samples.

PMID- 11848396
TI  - T vectors with endoglucanase A (celA) gene for direct detection of PCR clones.

PMID- 11848397
TI  - 6xHis promotes binding of a recombinant protein to heparan sulfate.

PMID- 11848398
TI  - High-yield purification of functional, full-length steroid receptor coactivator 1
      expressed in insect cells.

PMID- 11848399
TI  - TGGE-STAR: primer design for melting analysis using PCR gradient gel
      electrophoresis.

PMID- 11848400
TI  - Novel energy transfer fluorescence labeling cassette.

PMID- 11848401
TI  - Early shape-shifting FRET probe.

PMID- 11848402
TI  - Confocal reflection microscopy: the "other" confocal mode.

PMID- 11848403
TI  - Chimerism analysis in sex-mismatched murine transplantation using quantitative
      real-time PCR.
AB  - Marine experimental stem cell transplantations require the accurate
      discrimination and quantification of donor cells from host cells. A Y-chromosome
      specific, quantitative real-time PCR (kinetic PCR) protocol for blood-derived DNA
      was developed. The assay sensitivity was extremely high with accurate detection
      of only 10 pg (six copies of Y target DNA) in a variable background of female DNA
      background ranging from 2.5 to 50 ng. The dynamic range of the assay provided
      accurate results ranging from 2.2 x 10(-2)% to 100% of male DNA in female
      background. The kinetic PCR assay can be used in all mouse strains, and a sample
      size as low as 2.5 ng total DNA is sufficient for analysis. Therefore, kinetic
      PCR allows engraftment kinetic studies on repeated blood draws of individual
      animals with no need for sacrifice. Compared to conventional PCR, the assay is
      much simplified, as neither the accurate adjustment of sample DNA concentration
      nor a post-reaction analysis procedure is required. The procedure is simple, free
      of radioactivity, and permits a throughput of 500-600 reactions per day.

PMID- 11848404
TI  - Red fluorescent protein DsRed from Discosoma sp. as a reporter protein in higher
      plants.
AB  - GFP from Aequorea victoria is a standard genetic marker widely used to visualize
      cellular events in a noninvasive manner. For simultaneous imaging of different
      processes, in vivo mutants of GFP with shifted wavelength spectra (e.g., blue
      fluorescent protein) are conventionally used. The recently reported red
      fluorescent protein from Discosoma sp., DsRed, represents a new marker that can
      be used together with GFP variants for multicolor imaging. DsRed is an
      interesting marker protein for use in plants because of its red-shifted
      wavelength spectrum that will avoid damaging cells and tissues by excitation
      light. In this report, we show that DsRed is an excellent marker in higher plants
      in spite of the interfering red autofluorescence of chlorophyll, which can be
      eliminated by using the appropriate filter sets. Transient expression of DsRed1
      C1 and a soluble-modified, red-shifted GFP variant has been carried out both
      individually and jointly in the epidermal cells of three different Nicotiana
      species and Chenopodium quinoa, which gives rise to dual labeling in plants. For
      this purpose, a human codon-optimized variant of DsRed has been adopted for
      expression in plants. Moreover, the DsRed reporter gene was expressed by using a
      labeled plant viral vector derived from an infectious full-length clone of potato
      virus X.

PMID- 11848405
TI  - Fixation and decalcification of adult zebrafish for histological,
      immunocytochemical, and genotypic analysis.
AB  - To facilitate the molecular analysis of tissues in adult zebrafish, we tested
      eight different fixation and decalcification conditions for the ability to yield
      DNA suitable for PCR and tissue immunoreactivity, following paraffin embedding
      and sectioning. Although all conditions resulted in good tissue histology and
      immunocytochemistry, only two conditions left the DNA intact as seen by PCR. The
      results indicate that zebrafish fixed in either 10% neutral buffered formalin or
      4% paraformaldehyde, followed by decalcification in 0.5 M EDTA, is an easy and
      reliable method that allows molecular experiments and histology to be performed
      on the same specimen. The fixation and decalcification by Dietrich's solution
      permitted the PCR amplification of DNA fragments of 250 but not 1000 bp.
      Therefore, a protocol of formalin or paraformaldehyde fixation followed by
      decalcification with EDTA is broadly applicable to a variety of vertebrate
      tissues when excellent histological, immunocytochemical, and genotypic analyses
      may be simultaneously required.

PMID- 11848406
TI  - Rapid construction of sequencing templates by random insertion of antibiotic
      resistance genes.
AB  - We describe a novel and handy method for generating a population of templates for
      sequencing. The method is based on the random insertion of antibiotic resistance
      gene in plasmid DNA digested by DNase I. The advantages of this approach are the
      small quantity of DNA necessary for mutagenesis and the complete independence
      from the restriction map of the plasmid. DNase I digestion provides a random
      distribution of the insertions, while antibiotic selection provides low
      background. We also present a convenient PCR-based procedure for the analysis and
      ordering of obtained insertion mutants.

PMID- 11848407
TI  - Microgel assessment of nucleic acid integrity and labeling quality in microarray
      experiments.

PMID- 11848408
TI  - Method of RNA purification from endothelial cells for DNA array experiments.

PMID- 11848409
TI  - Detection of diluted gene expression alterations using cDNA microarrays.
AB  - The use of DNA microarrays has spanned numerous disciplines of life science
      research. Despite the volume of studies utilizing this technology, no consensus
      exists on basic issues such as the determination of significantly altered genes
      in a given experiment, often leading to either false-negative or false-positive
      data. In this report, we study the effect of dilution of biological alterations
      on the detection level of gene expression differences using cDNA microarrays. We
      propose that subtle alterations in transcript levels of genes below the 2-fold
      level should be considered when replicate hybridizations are performed, because
      these subtle gene expression changes may be due to a robust response in few
      cells. We measured the effect of dilution of gene expression and found that
      differences in gene expression between the two cell lines assayed (HaCaT and MCF
      7) were detected even after a 20-fold dilution factor. These results better our
      understanding of biological alterations that comprise a relatively small
      percentage of an assayed organ and help in the interpretation of gene expression
      data.

PMID- 11848410
TI  - Correcting for signal saturation errors in the analysis of microarray data.
AB  - A variety of technical errors have arisen in data analysis when using cDNA or
      oligonucleotide microarrays. One of the most insidious problems is the saturation
      of the hybridization signal of high-abundant transcripts. This problem arises
      from the truncation of the laser fluorescence signal. When the hybridization
      signal on the microarray is very strong, this truncation can result in serious
      consequences that may not be readily apparent to the user. As an illustration of
      this problem, two subclasses of normal human tissue samples (six liver and six
      lung samples) were analyzed with GeneChip probe arrays to evaluate the patterns
      of expression for approximately 7000 human genes. Five of these data sets were
      found to suffer from signal truncation. This caused several tissues to be
      incorrectly classified using hierarchical clustering. To rectify this problem so
      that the gene expression data could be properly compared and clustered, we
      developed a "filtering" procedure that identifies a subset of genes least
      affected by the signal saturation. This filtering procedure can be obtained at
      www.hugeindex.org.

PMID- 11848411
TI  - MarC-V: a spreadsheet-based tool for analysis, normalization, and visualization
      of single cDNA microarray experiments.
AB  - The comprehensive analysis and visualization of data extracted from cDNA
      microarrays can be a time-consuming and error-prone process that becomes
      increasingly tedious with increased number of gene elements on a particular
      microarray. With the increasingly large number of gene elements on today's
      microarrays, analysis tools must be developed to meet this challenge. Here, we
      present MarC-V, a Microsoft Excel spreadsheet tool with Visual Basic macros to
      automate much of the visualization and calculation involved in the analysis
      process while providing the familiarity and flexibility of Excel. Automated
      features of this tool include (i) lower-bound thresholding, (ii) data
      normalization, (iii) generation of ratio frequency distribution plots, (iv)
      generation of scatter plots color-coded by expression level, (v) ratio scoring
      based on intensity measurements, (vi) filtering of data based on expression level
      or specific gene interests, and (vii) exporting data for subsequent multi-array
      analysis. MarC-V also has an importing function included for GenePix results
      (GPR) raw data files.

PMID- 11848412
TI  - Four-laser scanning confocal system for microarray analysis.
AB  - We have constructed a confocal scanner suitable for routine microarray analysis
      from commercially available parts. We have outlined the details that should be
      considered when designing such an instrument and listed some of the specific
      components comprising the system [the full list of system components is available
      on CD from the corresponding author (D.J.G.) at no charge]. Here, we describe the
      methods used to test the linearity and sensitivity of the instrument. Performance
      was evaluated with two commonly used dyes, fluorescein and Cy5. While the
      instrument had a linear correlation between the dye concentration and
      fluorescence intensity, the observed deviation from a slope of 1.0 underscores
      the importance of running multipoint calibration experiments to obtain accurate
      dye quantitation over the full dynamic range of the scanner. This method has
      utility in testing commercial instruments in addition to the scanner described
      here. An array with over 300 spots dyed with Cy3 was scanned with our instrument
      and a high-end commercial instrument. The agreement between the two instruments
      was very good over a 1000-fold intensity range. Our scanner is a cost-effective
      alternative to more costly commercial scanners with similar capabilities.

PMID- 11848414
TI  - Role of short tandem repeat DNA in forensic casework in the UK--past, present,
      and future perspectives.
AB  - The analysis of short tandem repeat (STR) DNA sequences is of fundamental
      importance to forensic science because they have become the recognized standard
      in constructing national public databases. Consequently, considerable effort has
      been expended in developing multiplexed (one tube) reactions that analyze several
      loci in combination. The implementation of STRs in casework cannot take place
      without a full understanding of the systems used. The purpose of validation is to
      characterize multiplexes when one is challenged with forensic samples. For
      example, mixtures are often encountered that may be particularly difficult to
      interpret against a background of allelic artifacts. By increasing the number of
      PCR amplification cycles, it is possible to dramatically boost the sensitivity of
      the system so that just a handful of cells may be successfully analyzed. However,
      interpretation is much more complex because the origin of DNA profiles may be
      less certain and complicated by issues such as contamination, the potential for
      innocent transfer and a predominance of mixtures. This review provides a brief
      historical background of the development of STRs in forensic casework that
      culminated in the creation of national DNA databases. The development of
      guidelines to interpret complex DNA profiles, such as mixtures, is outlined.
      Finally, the recent innovation of low copy number DNA profiling is explained
      along with the special considerations needed to report in court.

PMID- 11848413
TI  - Analysis of microliter volumes of dye-labeled nucleic acids.
AB  - We describe methodology useful for determining the fluorescent activity of small
      volumes (e.g., 1 microL) of dye-labeled cDNAs using microabsorbance spectroscopy.
      A direct relationship was found between the average fluorescent hybridization
      signal from an array and the fluorescent activity of the cDNA used in the
      hybridization. The microabsorbance method makes possible the screening of small
      volume samples before hybridization, allowing for a more efficient use of
      available microarrays. The standardization of the concentration of RNA samples
      contained in 1 microL before reverse transcription is also described.

PMID- 11848415
TI  - Genetic tools for pseudomonads, rhizobia, and other gram-negative bacteria.
AB  - Gram-negative bacteria are extraordinarily diverse microorganisms that present a
      wide variety of characteristics worthy of genetic investigation. For historical
      reasons, the application of recombinant DNA technology to gram-negative bacteria
      in general has always lagged behind that of E. coli and its close relatives.
      However, the past 10 years have seen dramatic advances in the development of new
      tools and vectors for genetic analysis in non-E. coli hosts. Applications include
      various kinds of genetic manipulation, conjugation, transposition, site-specific
      recombination, protein secretion, protein purification, cell suicide, microbial
      ecology, biodegradation, and plant and animal pathogenicity.

PMID- 11848416
TI  - Generation of von Willebrand factor epitope libraries expressed in E. coli.
AB  - The von Willebrand factor (VWF) subunit is composed of several domains, often
      coinciding with structural regions, characterized through their specific
      interaction with a ligand. Since several monoclonal antibodies (MoAbs) have been
      shown to functionally interfere with one of the specific interactions, we have
      created libraries of bacterial clones expressing peptidic sequences of VWF to map
      antibodies directed against this protein. Randomly cleaved fragments of VWF cDNA
      have been cloned in a plasmid designed for the expression of small peptides as
      part of larger fusion proteins. The NovaTope system is a useful procedure for
      protein analysis, allowing screening of epitopes composed of contiguous amino
      acid residues. To map MoAbs with conformational discontinuous epitopes displayed
      on small as well as large peptidic domains, this technique had to be widely
      modified to obtain two VWF peptide libraries expressing two ranges of peptide
      length (15-70 and 100-300 amino acids). Screening with six MoAbs with an epitope
      in a known region was performed to control both libraries. Four MoAbs were mapped
      through the characterization of overlapping sequences for 5-10 different
      positively expressed clones respectively. Two of these mapped MoAbs had no known
      inhibitory effect and bind reduced VWF only. The fact that the two other MoAbs
      mapped VWF functional interactions with ligands, platelet GPIIb/IIIa and Factor
      VIII, respectively, demonstrate that our libraries are valuable tools to
      determine conformational epitopes.

PMID- 11848417
TI  - Solid-phase PCR in microwells: effects of linker length and composition on
      tethering, hybridization, and extension.
AB  - During the solid-phase PCR (SP-PCR), DNA oligonucleotides complementary to a
      soluble template and immobilized on a surface are extended in situ. Although
      primarily used for pathogen detection, SP-PCR has the potential for much broader
      application, including disease diagnostics, genotyping, and expression studies.
      Current protocols for SP-PCR in microwells are suitable for enzymatic detection
      of immobilized products, but yields are generally insufficient for direct
      detection of products using conventional fluorescent probes. Here, we
      quantitatively measure the outcome of tethering, hybridization, and solid-phase
      extension, and examine the effect of composition and length of the spacer at the
      5' end of tethered oligonucleotides. Our results indicate that steric hindrance
      primarily affects polymerase activity rather than the efficiency of hybridization
      between the template and the tethered oligonucleotide. SP-PCR yields are
      significantly higher for a five-unit hexaethyleneglycol (HEG) spacer than for the
      more commonly used 10-residue deoxythymidine spacer. The optimal 5' HEG spacer
      resulted in a 60-fold increase in extension efficiency relative to a previously
      reported value for SP-PCR on a glass surface. Thus, optimized spacers should
      allow direct quantification of SP-PCR products, providing a simple, quantitative,
      and cost effective means of sample analysis for a variety of applications.

PMID- 11848419
TI  - Species identification and confirmation of human and animal cell lines: a PCR
      based method.
AB  - Misidentification and cross-contamination of cell lines are major problems of
      cell cultures that can make scientific results and their reproducibility
      unreliable. This paper describes a PCR-based method for easily identifying or
      confirming the species of origin of cell lines by using a panel of
      oligonucleotides specific for the nine animal species most common in cell culture
      laboratories. A panel of 35 human and animal cell lines, whose species of origin
      were previously confirmed by isoenzyme assay, was studied with nine species
      specific primer pairs that specifically anneal to DNA sequences codifying for
      human, cat, dog, mouse, rat, horse, rabbit, African Green monkey cytochrome c
      oxidase subunit I (cox I), and one primer pair specific for the cytochrome b gene
      of Chinese hamster. The amplified fragments were analyzed by electrophoresis in
      ethidium bromide-stained 2% agarose gels. The method is simple, rapid, highly
      sensitive, and useful for routinely monitoring the species identity of cell
      cultures.

PMID- 11848418
TI  - Epitope tagging genomic DNA using a CD-tagging Tn10 minitransposon.
AB  - Here, we describe an efficient system for epitope tagging cloned genes by CD
      tagging using a mini-Tn10 transposon delivery vector. The system was tested
      against a lambdaFIX genomic clone of the human nucleolin gene. Transfection of
      HeLa cells with the tagged gene led to the expression of both the appropriately
      spliced tagged transcript and the appropriately localized tagged protein.

PMID- 11848421
TI  - Association between invasive squamous cell carcinoma and lichen sclerosus et
      atrophicus.

PMID- 11848420
TI  - Nonradioactive assay of FLAG-tagged MAPK using ANTI-FLAG antibody-coated
      multiwell plates.
AB  - We have developed a rapid, sensitive, and quantitative 96-well microplate-based
      nonradioactive immunoprecipitation/kinase assay to evaluate mitogen-activated
      protein kinase (MAPK) activity. Three quantitative nonradioactive
      imunoprecipitation/kinase assays of MAPK were demonstrated on a 96-well
      microplate coated with ANTI-FLAG M2 antibody (ANTI-FLAG M2 plate): (i) the
      capture of phosphorylated FLAG-tagged MAPK fusion protein (FLAG-MAPK) from
      phorbol esters-stimulated, FLAG-MAPK-transfected COS-7 cells, coupled with a very
      sensitive ELISA procedure to quantitate the level of phosphorylation of FLAG
      MAPK; (ii) the in vitro kinase reaction of FLAG-MAPK activity with a substrate
      and ATP in the same well used to captured the phosphorylated FLAG-MAPK; and (iii)
      the in vitro kinase reaction of captured non-activated FLAG-MAPK by its upstream
      kinase from phorbol 12-myristate 13-acetate (PMA)-stimulated COS-7 cells. These
      results demonstrate that the ANTI-FLAG M2 plate allows for the rapid and
      quantitative determination of phosphorylation of FLAG-MAPK directly from
      stimulated, transfected cell lysate. Captured, phosphorylated FLAG-MAPK retains
      catalytic activity as demonstrated by the phosphorylation of Elk-1 in the same
      well. Furthermore, phosphorylation of captured FLAG-MAPK by the upstream kinases
      can be observed directly on the plate. These assays are sensitive, specific, and
      suitable for handling multiple samples. Thus, the ANTI-FLAG M2 plate forms the
      basis of a high-throughput screening platform in kinase analysis.

PMID- 11848422
TI  - Blood vessels are regulators of growth, diagnostic markers and therapeutic
      targets in prostate cancer.
AB  - The vasculature plays an important role in the normal and malignant prostate.
      Under basal conditions both glandular epithelial and stromal prostate cells
      produce an abundance of blood flow and angiogenesis regulating substances and the
      expression of these is generally increased in prostate tumors. The proportion of
      proliferating endothelial cells is high in the normal prostate compared to other
      tissues in the body. After castration effects on the vasculature, such as
      decreased blood flow and vascular regression, precede effects on the glandular
      compartment. Correspondingly, hormone induced prostate growth is characterized by
      early effects on the vasculature such as increased blood flow and endothelial
      cell proliferation, thus indicating that the vasculature may be involved in the
      androgenic regulation of the prostate. Prostatic intraepithelial neoplasia (PIN)
      and prostate cancer are associated with increased vascular density and in
      experimental models prostate cancer growth is apparently angiogenesis-dependent
      since tumor growth and progression can be inhibited by antiangiogenic treatment.
      Moreover, vascular density has been related to prognosis in prostate cancer
      patients. A better understanding of the pathways regulating angiogenesis in the
      normal prostate and how these pathways change during malignant transformation can
      hopefully lead to better prognostic markers and therapies for the large group of
      patients with prostate cancer. The purpose of this review is therefore to
      summarize the current knowledge on the role and regulation of the vasculature in
      the prostate and its potential clinical applications.

PMID- 11848423
TI  - Relatively high risk of treatment failure after prostatectomy: tumour grade,
      histopathological stage and the preoperative serum PSA level are key
      prognosticators.
AB  - OBJECTIVE: Prostate cancer is the most common malignancy among males in Sweden.
      Any reduction in morbidity and mortality would require early detection of cases
      in which curative treatment is achievable. MATERIAL AND METHODS: From 1994
      through 1998. 105 patients with clinically localized T1-T2 tumours were subjected
      to radical prostatectomy at our department. Three patients were lost to follow
      up. We obtained clinical information from the patients' medical records and used
      pathologist reports to characterize the tumours with respect to grade and
      histopathological stage. We used serum PSA levels as a surrogate end-point, with
      a level equal to or above 0.6 ng/ml designated as treatment failure. Outcome was
      examined with respect to tumour grade, histopathological stage and preoperative
      PSA level. RESULTS: Altogether, 29% of the patients showed PSA failure during
      follow-up which varied between 2 and 6 years. No mortality due to prostate cancer
      was recorded during this time period. We found that tumour grade,
      histopathological staging and as well as the preoperative PSA level correlated
      with treatment failure (p<0.01). About 80% of the patients with a preoperative
      PSA <10 ng/ml showed no signs of treatment failure. The corresponding figure for
      those with PSA above 10 ng/ ml was 55%. The outcome for patients with a PSA
      between 10-20 did not seem to be better than that for patients with a
      preoperative PSA >20 ng/ml. CONCLUSION: Our study indicates, that the risk of
      treatment failure depends strongly on the grade of the tumour and increases when
      preoperative PSA value is greater than l0 ng/ml.

PMID- 11848424
TI  - Invasive urodynamic studies are well tolerated by the patients and associated
      with a low risk of urinary tract infection.
AB  - OBJECTIVE: An essential part of investigation of the lower urinary tract is
      pressure/flow studies (pQS). In fact, pQS is the only way of diagnosing bladder
      outlet obstruction. There is controversy regarding whether or not prophylactic
      antibiotic treatment is necessary. This prospective study was carried out in
      order to determine the frequency of infections and/or distress after pQS
      performed without the use of antibiotic prophylaxis. MATERIAL AND METHODS: One
      hundred and twenty-three patients were included in the present study, all males.
      They were requested to answer a questionnaire I week after pQS. Questions were
      asked concerning symptoms of voiding disorders, dysuria, hematuria, incidence of
      fever and the patient's acceptance of the investigation after the pQS procedure.
      Urine was obtained for culture immediately before the investigation and 3 and 7
      days after the pQS. RESULTS: Forty-six per cent of the patients experienced some
      degree of transient dysuria after pQS. and 18.5% experienced voiding problems of
      varying nature. Five per cent of the patients had hematuria and 2.5% reported
      fever. Fifty per cent of the patients experienced some degree of discomfort
      during the pQS investigation, and 4.1% had positive culture and symptoms of UTI
      requiring antibiotic treatment. CONCLUSIONS: PQS is well accepted by the patients
      and the regular use of propylactic antibiotics is not indicated. We recommend,
      though, that patients at risk for serious complications from infections (e.g.
      those with prosthetic heart valves) should receive prophylactic antibiotics.

PMID- 11848425
TI  - Can urodynamic assessment of outflow obstruction predict outcome from watchful
      waiting?--A four-year follow-up study.
AB  - OBJECTIVE: One of the most common "treatment" alternatives in suspected outflow
      obstruction due to bladder outlet obstruction (BOO) is watchful waiting (WW). The
      aim of this study was to see whether there were any differences in outcome
      between patients with slight, moderate or severe obstruction due to BOO as
      classified by transrectal ultrasound (TRUS) and urodynamics. MATERIAL AND
      METHODS: Thirty-seven men with lower urinary tract symptoms (LUTS) and suspected
      BOO were included. All of the patients were investigated by a routine
      investigation schedule, including TRUS and urodynamics with pressure-flow
      measurement (pQS) at baseline. Patients with cancer in the urinary tract,
      prostatitis, history of detrusor hyperreflexia (peripheral or central diseases or
      trauma to the nervous system affecting the bladder) and serious systemic diseases
      were excluded. Patients were examined at baseline, then checked again after 1
      year and 4 years. Patients who did not want to continue with WW were listed as
      treatment failures. RESULTS: At baseline, 43.2% of the patients were
      urodynamically severely obstructed and 32.3% were moderately obstructed. Thirty
      five per cent of the patients were found to have previously unknown detrusor
      hyperactivity/overactivity. The prevalence of detrusor hyperactivity/overactivity
      increased with BOO. After 1 year, IPSS had decreased at unchanged Qmax and
      postresidual volume. These findings persisted at 4 years. The failure rate
      increased in the more obstructed patients and was significantly higher with more
      severe obstruction. Complications were found in 13.5%, with no significant
      differences between patients with minor BOO [Detrusor Adjusted Mean PURR Factor
      (DAMPF) scale <42], moderate BOO (DAMPF 42-65) and severe BOO (DAMPF >65).
      CONCLUSIONS: In patients with severe BOO, the LUTS and failure rate increase over
      time. The percentage of patients with detrusor hyperactivity/overactivity was
      higher in the severely obstructed group. By including full urodynamics when
      investigating patients with BOO, it seems possible to predict the failure rate
      according to the patients' obstruction grade. This gives an opportunity to treat
      the patient with minimal invasion, and to give the individual patient a more
      precise prognosis if WW is preferred.

PMID- 11848426
TI  - Pressure-flow studies for patient selection in the treatment of symptomatic BPH-
      a one-year follow-up study.
AB  - OBJECTIVE: Many different treatments for lower urinary tract symptoms (LUTS) due
      to bladder outlet obstruction (BOO) are available today. To select the most
      suitable method for each patient is therefore a delicate task. The aim of this
      study has been to use a standardised systematic investigation schedule including
      pressure flow studies (pQS) in order to try to use graded treatment according to
      obstruction. METHODS: Ninety-nine patients were systematically examined with
      routine investigations and pQS to select between 3 treatment options, TURP, TUMT
      2.0 (low energy) and watchful waiting (WW). Patients with severe BOO were
      recommended TURP, patients with moderate BOO were treated with TUMT and patients
      with no or minor BOO were recommended WW. RESULTS: TURP produced the best
      improvement in maximum free flow (Q-max), IPS-score and PVR, but only TURP had
      serious complications. TUMT treatment produced a more moderate improvement in
      flow rate, IPS-score and PVR, and all of the complications were minor. WW did not
      improve PVR or Q-max but the IPS-score decreased significantly. One UTI was the
      only complication in the WW group. CONCLUSIONS: pQS can be used to allocate
      patients with LUTS due to suspected BOO into different treatment arms; TURP,
      TUMT, WW, all with known different effects of BOO and with different severity of
      complications. Good symptomatic effect in Q-max, PVR and IPS-score with less
      serious complications and at low failure rate can thereby be obtained.

PMID- 11848427
TI  - Visual analogue scale, urinary incontinence severity score and 15 D--psychometric
      testing of three different health-related quality-of-life instruments for urinary
      incontinent women.
AB  - OBJECTIVE: The purpose of this study is psychometric assessment of disease
      specific questionnaire, Urinary Incontinence Severity Score (UISS) and Visual
      Analogue Scale (VAS) in urinary incontinent women. We also investigated
      functional relationship between UISS, VAS and 15D-valid, generic health-related
      quality-of-life (HRQoL) instrument. MATERIALS AND METHODS: Eighty-two incontinent
      female patients were recruited for the study that included baseline investigation
      and re-evaluation 13 months (range 6-21 months) after treatment. Twenty-nine
      control women who had urinary incontinence but were not bothered by it completed
      the HRQoL measurements. RESULTS: Internal consistency and content validity of
      UISS was good. Both measures UISS and VAS were reproducible, Spearman's rank
      correlation between test-retest were 0.88 and 0.85 respectively. The control
      women's UISS, 15D and VAS scores were significantly lower than the patient's
      scores (p<0.001, Mann-Whitney U test) which proves to be a good discriminant. The
      changes in pad test correlated moderately well with those in the VAS and UISS.
      The UISS, VAS and 15D in the improved group had responsiveness (Guyatt's)
      statistics: 1.48, 1.74 and -0.80 respectively. CONCLUSION: The UISS and VAS
      proved to be valid, reproducible and responsive to treatment for UI women. The
      functionality of the 15D was good but it demonstrated less sensitivity to changes
      after treatment.

PMID- 11848428
TI  - Tension-free vaginal tape evaluated using patient self-reports and urodynamic
      testing--a two-year follow-up.
AB  - OBJECTIVE: Urinary incontinence entails both reduced quality of life for many
      women and considerable public expense. Compared with other methods aimed at
      alleviating incontinence, tension-free vaginal tape (TVT) is minimally invasive,
      can be performed under local anaesthesia and results in less morbidity and
      shorter hospitalization. The present study was carried out to evaluate early and
      late complications and as a 2-year follow-up after surgery. MATERIAL AND METHODS:
      In 1996-98, 75 women underwent TVT sling plasty; mean time for surgery was 39 min
      and for hospitalization 24 h. The procedure caused bladder perforation in 3
      women, but this was detected by cystoscopy and immediately corrected.
      Postoperative retention occurred in 9 patients but was transient. RESULTS: After
      surgery 80% were cured, 9% showed improvement and 11% were failures. Two women
      exhibited vaginal erosion, and one of these had previously undergone radiation
      therapy. One sling caused obstruction and had to be cut. Improvements included
      less impact on social and physical activities and mental status and significant
      reduction of voiding frequency, leakage episodes and pad use. CONCLUSIONS: The
      TVT technique seems to provide results comparable with those obtained with Burch
      colposuspension, but it entails less risk of obstruction than previous slings
      techniques because it causes no compression of the urethra. TVT is effective in
      women with genuine stress incontinence due to urethral hypermobility and in
      elderly women with sphincter incompetence, although the outcome is better in the
      former.

PMID- 11848429
TI  - Management of postoperative obstruction after bulboprostatic anastomotic
      urethroplasty for membranous urethral defects secondary to pelvic fracture.
AB  - OBJECTIVE: To present our experience in the management of postoperative
      obstruction after bulboprostatic anastomotic urethroplasty for post-traumatic
      membranous urethral defects secondary to pelvic fracture. MATERIAL AND METHODS:
      Between 1979 and 1998 we managed 25 patients with postoperative posterior
      urethral obstruction after bulboprostatic anastomotic urethroplasty. Of these
      patients, 17 had undergone one repair and 8 had undergone more than one repair.
      One case had multiple perineal fistulae. Visual urethrotomy was done in 3
      patients, 1 had cross union at the site of the anastomosis, and the other 2 had
      short passable strictures. In cases of obliterated strictures, bulboprostatic
      anastomosis was done in 6 patients via the perineal route and in 10 patients via
      the transpubic route. In 6 patients the urethral obstruction was due to new bone
      formation (callus) in the pubic gap (after pubectomy) pressing on the anastomatic
      line, and these cases were treated by removal of the callus. RESULTS: After 1-6
      years of follow up (mean 3.16 years) the outcome of the 3 patients who underwent
      visual urethrotomy was good. Eleven of the 16 patients who underwent anastomotic
      urethroplasty (68.7%) void well, 2 patients had fair results and the remaining 3
      (18.7%) had restenosis. In the 6 patients who had new bone formation in the pubic
      gap, the obstruction was relieved by removal of the callus. CONCLUSIONS: Visual
      urethrotomy is limited to very short passable urethral strictures, we do not
      recommend cutting on the light. End-to-end anastomosis was performed in
      obliterated strictures. Removal of the new bone formation from the pubectomy gap
      relieved the urethral obstruction.

PMID- 11848430
TI  - The results of routine evaluation of adult patients with haematuria analysed
      according to referral form information with 2-year follow-up.
AB  - OBJECTIVE: With the principal aim of determining how often investigation of
      haematuria results in a malignancy diagnosis, the referrals (n = 581) during one
      year to a department of urology (catchment area 250,000 inhabitants) where
      haematuria was mentioned in the referral form have been registered and analysed.
      The case records were evaluated after two years. RESULTS: The tumours detected
      were mainly bladder tumours (n = 43) and prostate cancers (n = 31). Only three
      upper urinary tract tumours were diagnosed. The incidence of malignancies was
      high in patients with macroscopic haematuria (24%), especially if it was
      asymptomatic (32%). The incidence was lower in microscopic haematuria (9%),
      especially if it was asymptomatic (5%). The incidence of malignancies was
      strongly age- and sex-related; in no female under 70 years and in no male under
      45 years of age with microscopic haematuria was a malignant tumour detected.
      CONCLUSION: Macroscopic haematuria, especially in older patients, is often
      associated with a malignancy and the investigation must be given high priority.
      The incidence of malignant tumours in patients with symptomatic microscopic
      haematuria also warrants an investigation. In the case of asymptomatic
      microhaematuria. the risk is so low, especially in women that the need for a work
      up must be strongly questioned.

PMID- 11848431
TI  - Comparative study of etofenamate and fentanyl for outpatient extracorporeal
      shockwave lithotripsy.
AB  - OBJECTIVE: This study aimed to compare the clinical efficacy and safety of
      etofenamate (a non-steroidal anti-inflammatory drug) and fentanyl (an opioid
      analgesic) for outpatient extracorporeal shock wave lithotripsy (ESWL). MATERIAL
      AND METHODS: 60 non-premedicated patients underwent ESWL for urinary tract
      calculus with the Multimed 2000 (ELMED Lithotripsy Co.. Turkey) lithotripter.
      None of patients had previous experience with ESWL treatment. The patients were
      divided into two groups. A single dose of 1 g etofenamate was given to the
      patients intramuscularly 25 min before ESWL in group I (n = 30) and 0.1 mg
      fentanyl was administered intravenously just before ESWL in group II (n = 30). At
      the end of the treatment a visual analogue score (VAS) of 0 (no pain) to 10
      (greatest pain) was used to evaluate the pain. Blood pressure, heart rate and
      arterial oxygen tension (PaO2) were measured before and during the ESWL. Groups
      were compared according to the pain scores, stone size, number of shocks, maximum
      voltage achieved, duration of ESWL and incidence of side-effects of the
      administered drug. Data were analysed with the Mann-Whitney U-test. RESULTS: No
      statistical differences were found between the two groups regarding achieved
      maximal energy levels, pain scores and number of shock waves given (p < 0.01).
      Satisfactory stone fragmentation was achieved in both groups. There were no
      changes in blood pressure or heart rate during the ESWL in either group. PaO2 was
      not affected in the etofenamate group, whereas a transient desaturation in two
      patients and giddiness in three patients were recorded in the fentanyl group.
      CONCLUSIONS: Both etofenamate and fentanyl have clinically sufficient effects on
      pain, and can be used safely for outpatient ESWL procedures.

PMID- 11848432
TI  - The place of the technique of narrowing neck of the dartos pouch on the ascent of
      testis after surgery.
AB  - OBJECTIVE: We aimed to compare the three techniques of dartos pouch orchiopexy,
      suture fixation to the scrotal wall and narrowing of the neck of pouch with or
      without suture fixation, in regard to the postoperative ascensus of testes.
      MATERIALS AND METHODS: We operated on 150 unilateral palpable undescended testis
      with the scrotal pouch orchiopexy technique. In this prospective study, patients
      were randomly divided into three groups: Testes were fixed to the scrotal wall in
      the first group, they were placed into the scrotal pouch without fixation but the
      neck of the dartos pouch was narrowed around the vas deferens and the vessels in
      the second group and testes were fixed to the scrotum with a suture and the
      dartos fascial opening was narrowed concomitantly in the third group. RESULTS:
      Patients were followed between 6 and 48 months (28.0 +/- 11.4). Only four testes
      of the first group (8.0%) were replaced upward after the operation where all the
      other two groups' testes were in their places. CONCLUSION: We believe that only
      narrowing of the dartos fascia around the vas deferens and vessels without
      fixation to the scotum prevents ascending of the testis upward after orchiopexy
      operations. We think this technique decrease the risk of supposed damage to the
      testicular tissue due to suture material.

PMID- 11848433
TI  - Expression of CD44 and major histocompatibility complex class II antigens
      correlate with renal scarring in primary and systemic renal diseases.
AB  - OBJECTIVE: Phenotypical changes in the tubular epithelial cells (TEC) seem to be
      important in the progression of renal diseases. The present study was designed to
      identify the relation between the expression of major histocompatibility complex
      (MHC) class II antigens and CD44 by TEC, with parameters of renal scarring in
      primary and systemic renal diseases. MATERIAL AND METHODS: Expression of MHC
      class II and CD44 antigens was determined immunohistochemically in 71 renal
      biopsies and eight nephrectomy specimens with chronic pyelonephritis (CP).
      RESULTS: CD44 expression was increased in renal diseases compared with autopsy
      cases and was strongly correlated with parameters of renal scarring and MHC class
      II antigen expression in primary and systemic renal diseases. CD44 expression was
      demonstrated in chronic pyelonephritis, postinfectious glomerulonephritis,
      diabetic nephropathy and hypertensive nephropathy, as well as other diseases
      described previously. Similar results were obtained for MHC class II antigen
      expression by TEC and these results were correlated with serum creatinine values.
      CONCLUSIONS: CD44 expression by TEC is a common pathway in renal scarring, like
      MHC class II antigen expression, and both of these may be important in renal
      scarring in CP cases as well as other primary and systemic renal diseases.

PMID- 11848434
TI  - Primary retroperitoneal pure yolk-sac tumor in an adult male.
AB  - Pure extragonadal tumors are rare in adult males. A 24-year-old male with an
      extremely high level of serum alpha-fetoprotein (32.795 ng/ml) was diagnosed by
      abdominal computed tomography as having a retroperitoneal tumor. A case of
      primary retroperitoneal pure yolk-sac tumor in an adult male is described.

PMID- 11848435
TI  - Malignant fibrous histiocytoma of the kidney.
AB  - Malignant fibrous histiocytoma (MFH) is extremely rare in the kidney. We present
      a case of primary renal MFH in a 55-year-old male and briefly review the disease.
      It is essential to differentiate MFH from more frequent renal cell carcinomas,
      because MFH represents a worse prognosis and requires different treatment.

PMID- 11848436
TI  - Risk of recurrent venous thomboembolism--expanding the frontier.

PMID- 11848437
TI  - Tissue-type plasminogen activator -7,351C/T enhancer polymorphism is associated
      with a first myocardial infarction.
AB  - We recently identified a polymorphic Sp1 binding site in an enhancer at the
      tissue-type plasminogen activator (tPA) locus (tPA -7,351C/T), which was
      associated with vascular tPA release. Subjects homozygous for the -7,351C allele
      had twice the tPA release rate compared to subjects carrying the -7,351T allele.
      In this study we tested the hypothesis that the tPA -7,351C/T polymorphism is
      associated with myocardial infarction (MI). In a population-based prospective
      nested case-control study within northern Sweden, genotypes were determined among
      61 MI cases and 120 controls. In a multivariate model, the tPA -7,351C/T
      polymorphism (OR 2.68 for T allele carriers; 95% CI 1.31-5.50), tPA antigen (OR
      1.16; 95% CI 1.07-1.25) and apo A-I (OR, 0.997; 95% CI 0.995-0.999) were
      independently associated with a first MI. These findings suggest that genetic
      markers of local tPA release and circulating steady-state tPA levels carry
      independent prognostic information.

PMID- 11848438
TI  - Enhancement of endogenous plasminogen activator-induced thrombolysis by
      argatroban and APC and its control by TAFI, measured in an arterial thrombolysis
      model in vivo using rat mesenteric arterioles.
AB  - Recent in vitro studies have demonstrated that thrombin inhibits fibrinolysis
      through thrombin-activatable fibrinolysis inhibitor (TAFI, plasma
      procarboxypeptidase B). We have recently shown that endogenous fibrinolysis in
      vivo is enhanced by activated protein C (APC) and the selective thrombin
      inhibitor, argatroban. The aim of the present study was to examine the role of
      TAFI in these fibrinolytic mechanisms in vivo using purified porcine pancreatic
      carboxypeptidase B (PPCPB) and a specific TAFIa inhibitor, potato tuber
      carboxypeptidase B inhibitor (PTCI) in a newly established arterial thrombolysis
      model. Non-occlusive, mural, platelet-rich thrombi were formed by helium-neon
      laser irradiation in rat mesenteric arterioles and thrombus size was measured by
      computerised image analysis. We confirmed that endogenous thrombolysis was
      enhanced by argatroban (2.0 mg/4 ml/kg/h) or APC (1.62 mg/ 2.31 ml/kg). PTCI (5.0
      mg/2 ml/kg) also accelerated endogenous thrombolysis. PPCPB (3.5 mg/2 ml/kg)
      inhibited thrombolysis in the absence and presence of argatroban or APC. PTCI
      tended to further promote APC-induced thrombolysis but the differences did not
      reach statistical significance. The present findings were in keeping with the
      results of earlier studies and demonstrated that arterial, platelet-rich thrombi
      in vivo are degraded by naturally generated plasminogen activators. TAFI may play
      a significant role in the control of these mechanisms.

PMID- 11848439
TI  - Prostaglandin endoperoxides and thromboxane A2 activate the same receptor
      isoforms in human platelets.
AB  - Arachidonic acid (AA) is a potent inducer of platelet aggregation in vitro; this
      activity is due to its conversion to biologically active metabolites,
      prostaglandin (PG) endoperoxides and thromboxane A2 (TxA2). PG endoperoxides and
      TxA, are thought to act on the same receptor; however, at least two isoforms of
      this receptor have been identified. The aim of our work was to clarify whether
      endoperoxides and TxA2 activate the same or different receptor subtypes to induce
      aggregation and calcium movements in human platelets. AA-induced aggregation and
      calcium rises were still detectable in platelets preincubated with thromboxane
      synthase inhibitors, which suppress TxA2 formation and induce PGH2 accumulation,
      suggesting that PG endoperoxides can activate platelets. Exogenously added PGH2
      was able to induce aggregation and calcium rises. Pretreatment of platelets with
      GR32191B or platelet activating factor, which desensitize one of the two receptor
      subtypes identified in platelets, did not prevent calcium rises induced by
      endogenously generated or by exogenouly added PGH2, indicating that TxA2 and PG
      endoperoxides share the same receptor subtype(s) to activate platelets. HEK-293
      cells overexpressing either of the two thromboxane receptor isoforms cloned to
      date (TPalpha and TPbeta) and identified in human platelets, stimulated with
      PGH2, or with the stable endoperoxide analog U46619, formed inositol phosphates.
      These data show that endoperoxides and TXA2 mediate their effects on platelets
      acting on both, and the same, receptor isoform(s).

PMID- 11848440
TI  - Short-term inhibition of ADP-induced platelet aggregation by clopidogrel
      ameliorates radiation-induced toxicity in rat small intestine.
AB  - Endothelial dysfunction and increased platelet aggregation may be involved in the
      pathogenesis of normal tissue radiation toxicity. This study assessed
      clopidogrel, an inhibitor of ADP-induced platelet aggregation, as a modulator of
      intestinal radiation injury (radiation enteropathy). Rat small intestine was
      exposed to 21 Gy X-radiation. Clopidogrel (20 mg/kg/day) or vehicle was
      administered from 2 days before to 10 days after irradiation. Structural
      radiation injury, neutrophil infiltration, smooth muscle cell proliferation,
      collagen content, and TGF-beta1 expression were assessed 2 weeks (early phase)
      and 26 weeks (delayed phase) after irradiation, using quantitative histology and
      immunohistochemistry, morphometry, and real-time fluorogenic probe RT-PCR.
      Irradiated intestine exhibited significant histopathologic injury, reduced
      mucosal surface area, vascular sclerosis, intestinal wall fibrosis, increased
      collagen content, and increased TGF-beta1 expression. Clopidogrel reduced ADP
      induced platelet aggregation by 93% and significantly attenuated the severity of
      post-radiation vascular sclerosis (p = 0.004 and p = 0.02) and the loss of
      mucosal surface area (p = 0.0008 and p = 0.003) at both 2 and 26 weeks.
      Clopidogrel also ameliorated overall histopathologic injury (p = 0.02), relative
      intestinal collagen content (p = 0.03), and collagen III immunoreactivity levels
      2 weeks after irradiation, and caused a borderline reduction in the radiation
      induced increase in extracellular matrix-associated TGF-beta immunoreactivity at
      26 weeks (p = 0.04). The effects of clopidogrel on steady-state TGF-beta1 mRNA
      levels and neutrophil infiltration were not statistically significant. Short-term
      clopidogrel administration affords protection against early and, to a lesser
      extent, delayed radiation enteropathy. Modulation of platelet aggregation should
      be subject to further studies as a potential method to increase safety and
      efficacy of radiation therapy.

PMID- 11848441
TI  - Human platelet Galphaq deficiency is associated with decreased Galphaq gene
      expression in platelets but not neutrophils.
AB  - G-proteins play an important role in platelet signal transduction and regulate
      responses upon activation of G-protein coupled receptors (GPCR). We have
      previously reported a patient with impaired platelet responses associated with
      deficiency in platelet Galphaq. To understand the molecular basis for this
      defect, the cDNA sequence encoding Galphaq (1080 bp) was obtained by reverse
      transcription and polymerase chain reaction of platelet RNA; the cDNA sequence
      showed no mutations in the patient. Platelet Galphaq mRNA levels were decreased
      by >50% compared to normal subjects; platelet Galphai2 mRNA levels were normal.
      Neutrophil calcium mobilization and elastase secretion, upon activation with
      several agonists, and neutrophil Galphaq mRNA and protein levels were normal.
      These studies demonstrate that the patient has a defect in Galphaq gene
      expression in platelets but not neutrophils, possibly due to defects in
      transcriptional regulation or mRNA stability, and suggest a hematopoietic-lineage
      specific defect.

PMID- 11848442
TI  - A cyclic pentapeptide derived from the second EGF-like domain of Factor VII is an
      inhibitor of tissue factor dependent coagulation and thrombus formation.
AB  - We have previously reported the finding of a cyclic dodecapeptide representing
      loop I of the second EGF-like domain of FVII, which inhibited TF-dependent FX
      activation (Orning et al. 1997). The biological activity was localized to the
      tripeptide motif, Glu-Gln-Tyr. We have now synthesized a cyclic analog of this
      motif, Cys-Glu-Gln-Tyr-Cys (PN7051), evaluated its anticoagulant and
      antithrombotic properties and performed a detailed structural characterization of
      the peptide. PN7051 is a dose-dependent inhibitor of TF-dependent FX activation
      and coagulation of plasma with IC50 values of 10+/-2 microM and 1.3+/-0.2 mM,
      respectively. It shows inhibitory efficacy on acute thrombus formation in an ex
      vivo model of human thrombosis using native blood. Fibrin deposition, platelet
      fibrin adhesion, platelet-thrombus formation, and thrombin-antithrombin complex
      formation were all inhibited by PN7051 at IC50 values between 0.3 and 0.7 mM. The
      cyclic peptide is a non-competitive inhibitor of FX activation with no
      significant active-site effects on FXa or FVIIa, indicating it affects FVII/TF/FX
      complex formation and function. Studies on the structure activity relationship
      revealed that Gln3-Tyr4, but not Glu2 were of importance for inhibition. In line
      with biological results, NMR measurements of PN7051 suggested that the Gln and
      Tyr residues configure a structural feature that contributes to the anticoagulant
      activity. Modeling of the Glu99Gln100Tyr101 motif in FVII and comparison with the
      solution structure of PN705 I suggest that the cyclic pentapeptide exerts its
      antithrombotic effect by interfering with the docking of Tyr101 into a
      hydrophobic pocket in the catalytic domain thereby disrupting an essential
      interaction between the second EGF-like and the catalytic domains of FVII.

PMID- 11848443
TI  - Catalytic antisense DNA molecules targeting Egr-1 inhibit neointima formation
      following permanent ligation of rat common carotid arteries.
AB  - Animal models of neointima (NI) formation have proven useful in gaining insights
      into the mechanisms of restenosis after coronary angioplasty and stenting, but
      the events at a molecular level remain incompletely understood. Here, we describe
      a technically straightforward, rat model of NI formation, involving complete
      ligation of the common carotid artery and demonstrate the importance of the
      immediate-early gene and zinc finger transcription factor Egr-1 in this process.
      Acute cessation of common carotid blood flow by vessel ligation, was followed by
      the expression of Egr-1 in the arterial media within 3 h and NI formation
      proximal to the point of ligation at 18 days. Local delivery of catalytic
      oligodeoxynucleotides (ODN) targeting rat Egr-1 mRNA at the time of ligation
      reduced both Egr-1 expression and NI formation in this model. In contrast, a
      scrambled version of this ODN had no inhibitory effect. These studies demonstrate
      for the first time that arterial intimal thickening following artery ligation is
      critically-dependent on the activation of Egr-1.

PMID- 11848444
TI  - Acute hyperglycaemia induces changes in the transcription levels of 4 major genes
      in human endothelial cells: macroarrays-based expression analysis.
AB  - Hyperglycaemia, in insulin-dependent or independent diabetes mellitus, promotes
      endothelial cell (EC) dysfunction and is a major factor in the development of
      macro- or microvascular diseases. The mechanisms and the disease-related genes in
      vascular diseases resulting from hyperglycaemia are poorly understood.
      Macroarrays. bearing a total of 588 cDNA known genes, were used to analyze HUVEC
      gene transcription subjected to 25 or 5-mM glucose for 24 h. Isolated mRNA
      derived from treated first passage HUVEC were reverse transcribed, 32P labeled,
      and hybridized to the cDNA macroarrays. Results show that acute hyperglycaemia
      induces an up-regulation of seven major genes, four of which were not previously
      reported in the literature. Northern blot analyses, performed on these 4 genes,
      confirm macroarrays results for alphav, beta4, c-myc, and MUC18. Moreover, time
      course analysis (0, 2, 4, 8, 2, 16, 24 h) of alphav, beta4 c-myc, and MUC18 mRNA
      expression, observed by northern blot assays, showed a peak at time points
      situated between 2 to 8 h. The 3 other genes (ICAM-1, beta1, and IL-8), were
      shown by others to be significantly upregulated after glucose stimulation.
      Furthermore, ELISA assays performed on the supernatant of HUVEC culture medium
      showed a significant increase of IL-8 for cells treated with 25-mM compared to 5
      mM glucose. Identified genes, upregulated in endothelial cells as a result of
      acute hyperglycaemia, may serve as therapeutic or diagnostic targets in vascular
      lesions present in diabetic patients. These results also demonstrate the use of
      cDNA macroarrays as an effective approach in identifying genes implicated in a
      diseased cell.

PMID- 11848445
TI  - The antimitogenic action of the sulphated polysaccharide fucoidan differs from
      heparin in human vascular smooth muscle cells.
AB  - The sulphated polysaccharides fucoidan and heparin both inhibit vascular smooth
      muscle cell (VSMC) proliferation. In this study we compared their actions on
      mitogenesis and ERK1/ERK2 activation in human VSMC. Although they displaced cell
      surface [3H]-heparin binding with similar affinity, they exerted clearly
      distinguishable actions. Fucoidan potently inhibited DNA synthesis stimulated by
      foetal calf serum, PDGF-BB and thrombospondin-1. Heparin inhibited the mitogenic
      action of serum and thrombospondin- I (though less potently than fucoidan), but
      failed to inhibit PDGF-BB-induced DNA synthesis. In parallel studies, fucoidan,
      but not heparin, inhibited ERK1/ERK2 activation by PDGF-BB. Moreover, fucoidan
      inhibited serum-induced mitogenesis in "heparin resistant" VSMC, which are
      refractory to heparin's antimitogenic action. In summary, the structurally
      different polysaccharides, heparin, fucoidan (and fucans) have distinguishable
      effects on mitogenesis and ERK1/ERK2 activation, suggesting that different
      mechanism(s) mediate these actions. The potent antimitogenic action of fucoidan
      and its efficacy in heparin resistant VSMC emphasise the need to further
      investigate its mechanism of action in human VSMC and suggest this agent could
      have therapeutic potential.

PMID- 11848446
TI  - Limitations of the laboratory monitoring of heparin therapy. Scientific and
      Standardization Committee Communications: on behalf of the Control of
      Anticoagulation Subcommittee of the Scientific and Standardization Committee of
      the International Society of Thrombosis and Haemostasis.

PMID- 11848447
TI  - A reference system approach to future standardization of laboratory tests for
      hemostasis. A position paper of the Joint Committee of the IFCC Scientific
      Division and the ISTH Scientific and Standardization Committee.

PMID- 11848449
TI  - Rapid intracellular degradation of a truncated mutant protein S (Q522X).

PMID- 11848448
TI  - Absence of mutations at the APC interacting sites of factor VIII in Caucasians.

PMID- 11848450
TI  - Evaluation of an enzymatic method to measure total homocysteine in plasma.

PMID- 11848451
TI  - Is homozygosity for the HR2 haplotype a risk factor for venous thromboembolism?

PMID- 11848452
TI  - A founder factor VIII mutation, valine 2016 to alanine, in a population with an
      extraordinarily high prevalence of mild hemophilia A.

PMID- 11848453
TI  - Gene targeting of components of the fibrinolytic system.
AB  - A number of in vitro and in vivo observations have implicated components of the
      fibrinolytic system in events associated with diverse physiological and
      pathophysiological processes, ranging from embryo implantation to cancer.
      Advances in gene targeting technology have led to the generation of mice
      deficient for components of the fibrinolytic system. Remarkably, these animals
      survive to adulthood with few spontaneous life threatening events. Thus, these
      mice are valuable resources for in vivo studies, not only for hemostasis-related
      research, but also for the relationships of these genes to other disease states
      associated with cellular growth and mobility, along with angiogenesis, vascular
      remodeling, inflammation, wound healing, and tumor growth and dissemination.

PMID- 11848454
TI  - FV HR2 haplotype as additional inherited risk factor for deep vein thrombosis in
      individuals with a high-risk profile.
AB  - A number of strongly linked polymorphisms within the Factor V gene (FV HR2
      haplotype) has been identified as a cause of resistance to activated protein C,
      and has suggested a modest risk factor for vein thrombosis. We investigated the
      frequency of the HR2 haplotype in 433 consecutive patients with confirmed deep
      vein thrombosis and 326 controls. The HR2 haplotype was more frequent in patients
      (15.2%) than in controls (10.1%). The risk of thrombosis among carriers of this
      haplotype was significantly increased (odds ratio: 1.6 [95% CI: 1.0-2.5]). The
      estimated risk associated with the HR2 haplotype was 1.8 (95% CI: 1.1-2.9) in
      subjects with (n = 255), and 1.4 (95% CI: 0.8-2.4) in those without (n = 178)
      acquired risk factors for vein thrombosis. After adjustment for sex, FV Leiden
      and FII A20210 mutations, the estimated risk of vein thrombosis among carriers of
      the HR2 haplotype was 1.8 (95% CI: 1.1-2.8). Present data indicate that the HR2
      haplotype is independently associated with vein thrombosis among individuals with
      a high-risk profile.

PMID- 11848456
TI  - The North American Immune Tolerance Registry: practices, outcomes, outcome
      predictors.
AB  - The North American Immune Tolerance Registry was initiated to study of immune
      tolerance (ITT) in Canada and the United States with respect to: 1) therapeutic
      regimens in use for haemophilia A (HA) and B (HB) inhibitor patients; 2)
      therapeutic outcomes; 3) potential predictors of successful outcome and 4)
      complications of therapy. Data on 188 ITT courses was collected by questionnaire
      from 60 haemophilia centers from 1993-99. Among the completed courses, the
      overall success rate was 70% (115/164) for all HA and 31% (5/16) for all HB.
      Outcome parameters noted to be predictive of ITT success for all HA were 1) pre
      ITT induction (p = 0.003), 2) ITT peak (p = 0.007) and 3) historical pre ITT peak
      (p = 0.04) inhibitor titres. An inverse correlation between total daily dose
      (units/kg/day) and success: (80% with under 50; 71% with 50-99; 73% with 100-199;
      and 41% with > or = 200, p = 0.01) was found. Outcome predictors were not
      evaluable for HB, although adverse reactions to therapy, including nephrotic
      syndrome, and access complications were more common among failed courses.
      Infection most often complicated the use of access catheters. These results are
      discussed within the context of the international ITT registry and upcoming
      prospective ITT study.

PMID- 11848455
TI  - Conformational transitions in factor VIIa: can we stabilize the inactive form of
      the enzyme?

PMID- 11848457
TI  - Plasma protein oxidation is associated with an increase of procoagulant markers
      causing an imbalance between pro- and anticoagulant pathways in healthy subjects.
AB  - The aim of the present study was to investigate whether the overall oxidation
      state of plasma proteins is associated with changes of circulating pro- and
      anticoagulant markers in healthy subjects (n = 99, 49 males, 50 females, aged
      from 6 to 91 yrs.). The carbonyl content of plasma proteins was measured and
      validated as an ex vivo index of the overall protein oxidation state due to its
      correlation with the plasma level of o-tyrosine (r = 0.87, P <0.0001), which is a
      well known oxidized product of L-phenylalanine. Using a multivariate analysis the
      carbonyl content of plasma protein was positively associated with procoagulant
      markers such as prothrombin F1 + 2 (r = 0.28, P = 0.0019) and fibrinopeptide A,
      (FpA) (r = 0.278, P = 0.003), as well as with the soluble derivative of the
      endothelial protein thrombomodulin (TM) (r = 0.469, P <0.0001). The procoagulant
      marker of thrombin activity, FpA, was significantly and positively correlated
      with the anticoagulant product of thrombin, namely the Protein C activation
      peptide (PCP), only in the tertile with low protein carbonyl content. At higher
      tertiles this correlation was no longer observed, thus suggesting a detrimental
      effect of oxidative stress on the TM/Protein C anticoagulant pathway. In 15
      subjects with high carbonyl content of plasma protein, treatment for 18 days with
      600 mg/d of vitamin E did not substantially modify the protein carbonyl content,
      the anticoagulant markers APC/PCP, and all procoagulant markers except F1+2,
      whose value significantly decreased by 25%. In conclusion, the present study
      shows that a high plasma protein oxidation ex vivo is associated with an overall
      hemostatic imbalance, which favors procoagulant markers. Vitamin E treatment in
      vivo restores only in part the equilibrium between pro- and anticoagulant
      pathways. This may open the way to further studies aimed at elucidating the
      mechanisms by which the oxidative stress is linked to activation of the
      coagulation system in atherothrombotic disorders.

PMID- 11848458
TI  - Thromboplastin-thrombomodulin-mediated time and serum folate levels are
      genetically correlated with the risk of thromboembolic disease: results from the
      GAIT project.
AB  - The GAIT (Genetic Analysis of Idiopathic Thrombophilia) Project is a family-based
      study dedicated to elucidating the genetic basis of hemostasis-related phenotypes
      and thrombosis risk. In this paper, we have examined several lesser-studied
      hemostasis-related phenotypes in the 21 GAIT families: levels of vitamin B 12,
      serum folate, whole blood folate, alpha2-antiplasmin, prekallikrein, beta2
      glycoprotein I, soluble P-selectin, factor XIII A and B subunits and a new
      coagulation measurement based on thromboplastin time in the presence or absence
      of thrombomodulin. Using the variance component method, we estimated the relative
      contributions of genetic and environmental influences on these phenotypes. In
      addition, we calculated the genetic correlations between thrombosis risk and each
      of these phenotypes. All 12 phenotypes showed significant genetic contributions
      with genes accounting for 22% to 78% of the variance after correction for
      covariate effects. Four phenotypes (three traits involving thromboplastin
      thrombomodulin mediated coagulation time and serum folate) exhibited significant
      genetic correlations with thrombosis. Thus, some of the genes that influence
      quantitative variation in these physiological phenotypes also influence the risk
      of thrombosis. The high heritabilities and significant genetic correlations
      between thrombosis and some risk factors suggest that joint consideration of
      correlated quantitative phenotypes will aid in identifying susceptibility genes.

PMID- 11848459
TI  - Risk of venous thromboembolism recurrence: high negative predictive value of D
      dimer performed after oral anticoagulation is stopped.
AB  - In some patients with previous venous thromboembolism (VTE) D-dimer levels (D
      Dimer) tend to increase after oral anticoagulant therapy (OAT) is stopped. The
      aim of our study was to evaluate the predictive value of D-Dimer for the risk of
      VTE recurrence after OAT withdrawal. After a first episode of deep vein
      thrombosis (DVT) of the lower limbs and/or pulmonary embolism (PE), 396 patients
      (median age 67 years, 198 males) were followed from the day of OAT
      discontinuation for 21 months. D-dimer was measured on the day of OAT withdrawal
      (T1), 3-4 weeks (T2) and 3 months (+/- 10 days, T3) thereafter. The main outcome
      events of the study were: objectively documented recurrent DVT and/or PE. D-dimer
      was found to be increased in 15.5%, 40.3% and 46.2% of the patients at T1, T2 and
      T3, respectively. In 199 (50.2%) patients, D-dimer levels were elevated in at
      least one measurement. During a follow-up of 628.4 years, 40 recurrences were
      recorded (10.1% of patients; 6.4% patient-years of follow-up). D-dimer was
      increased in at least one measurement in 28 of these cases, but remained normal
      in 11 subjects (three of whom had recurrent events triggered by circumstantial
      factors, three with malignancy-associated factors) (in one subject D-dimer was
      not measured). The negative predictive value (NPV) of D-dimer was 95.6% (95% CI
      91.6-98.1) at T3 and was even higher (96.7%; 95% CI 92.9-98.8) after exclusion of
      the six recurrences due to circumstantial factors. Only five idiopathic
      recurrences occurred in the 186 patients with consistently normal D-dimer. In
      conclusion, D-dimer has a high NPV for VTE recurrence when performed after OAT
      discontinuation.

PMID- 11848460
TI  - Evaluation of frozen plasma calibrants for enhanced standardization of the
      international normalized ratio (INR): a multi-center study.
AB  - Local ISI calibration has been proposed to improve INR accuracy and inter
      laboratory precision. We evaluated the affect of local PT calibration on INR
      precision and accuracy using six levels of frozen plasma calibrants prepared and
      pooled from normal donors and patients stabilized on sodium warfarin (coumarin)
      based oral anticoagulant therapy (OAT). Reference prothrombin time (PT) and INR
      values were assigned to these calibrants in accordance with World Health
      Organization (WHO) procedure using rTF 95 international reference preparation
      (IRP) of thromboplastin (human recombinant). These calibrants, along with five
      similarly characterized individual OAT patient plasmas, were distributed to 127
      laboratories in a multi-center study. Calibrant plasmas were evaluated and INR's
      subsequently determined on the 5 OAT test samples using: 1) the ISI and MNPT in
      place before the study (the local system), 2) the locally calibrated ISI value
      (local system with ISI calibration) and 3) a PT-INR calibration curve. Precision
      of INR results improved across the study group using the local system with ISI
      calibration and the PT-INR calibration curve methods, while accuracy of INR
      results improved using the PT-INR calibration curve approach only and not the
      local ISI calibration. The authors conclude that frozen plasma calibrants can be
      used locally to enhance precision and accuracy of PT results as reported in INR.
      These calibrants are effective over a range of reagents and instrument
      combinations. Furthermore, the PT-INR calibration curve appears to be the
      superior method for local calibration.

PMID- 11848461
TI  - Oxidized low-density lipoprotein associates strongly with carboxy-terminal domain
      of tissue factor pathway inhibitor and reduces the catalytic activity of the
      protein.
AB  - Tissue factor pathway inhibitor (TFPI) is a physiological protease inhibitor of
      the extrinsic blood coagulation pathway. Previously we have shown that TFPI
      associates quite rapidly with oxidized low-density lipoprotein (ox-LDL), with a
      reduction of the inhibitory activity on factor X activation. In the present
      study, it was found, by means of agarose gel electrophoresis, that the pre
      incubation of full-length rTFPI with heparin or the carboxy (C)-terminal part
      (peptide 240-265) of TFPI prevented the association with ox-LDL in a dose
      dependent manner. When rTFPI lacking the C-terminal basic part of the molecule
      (rTFPI-C) was mixed with ox-LDL, only a small amount of rTFPI-C was shifted to
      the position of ox-LDL on electrophoresis. Further, ox-LDL did not reduce the
      activity of rTFPI-C. These results indicate that the C-terminal domain of TFPI
      molecule plays a predominant role in the binding to ox-LDL and the binding
      through the C-terminal part is essential for the ox-LDL-dependent reduction of
      the anticoagulant activity of TFPI.

PMID- 11848462
TI  - Synergistic effect of thrombomodulin promoter -33G/A polymorphism and smoking on
      the onset of acute myocardial infarction.
AB  - Thrombomodulin is an endothelial cell surface receptor for thrombin. It plays an
      important role in the regulation of blood coagulation by decreasing thrombin
      activity and activating protein C. This study examined the possible association
      between the thrombomodulin -33G/A polymorphism and acute myocardial infarction.
      We recruited 278 patients (mean age 57.5 years, 241 men) with documented
      myocardial infarction and 450 age- and sex-matched control subjects. Polymerase
      chain reaction and single-strand conformation polymorphism was used to define the
      thrombomodulin -33G/A polymorphism. The frequency of the thrombomodulin GA+AA
      genotype among patients with myocardial infarction was higher than that in
      control subjects (22.7% vs. 16.2%, odds ratio [OR] 1.5, 95% confidence interval
      [CI] 1.0 to 2.2). The -33G/A polymorphism (GA+AA genotype) was significantly
      associated with myocardial infarction (OR 1.6, 95% CI 1.1 to 2.5) as was
      hypertension, diabetes mellitus and smoking. Among young myocardial infarction
      patients (age < or =45 years, n = 72), the frequency of -33G/A polymorphism was
      more significantly higher than that in control subjects (29.2% vs. 16.2%, OR 2.1,
      95% CI 1.2 to 3.8). The -33G/A polymorphism (OR 2.3, 95% CI 1.3 to 4.1) and
      smoking (OR 4.5, 95% CI 2.5 to 7.9) were the only independent risk factors for
      young myocardial infarction. Furthermore, among patients who did not smoke, the
      polymorphism was associated with a nonsignificant increase in the risk of young
      myocardial infarction (OR 1.9, 95% CI 0.6 to 5.6); whereas, in the presence of
      smoking, the increase was statistically significant (OR 2.3, 95% CI 1.2 to 4.7).
      Smoking carriers of the thrombomodulin -33G/A polymorphism had a nearly 10-fold
      increased risk of young myocardial infarction (OR 9.8, 95% CI 4.3 to 22.4) when
      compared with nonsmoking non-carriers. We concluded that there was a significant
      association between the thrombomodulin -33G/A polymorphism and myocardial
      infarction in our population, especially in young patients. The clinical effect
      of this genetic factor was enhanced by smoking.

PMID- 11848463
TI  - The APTT response of pregnant plasma to unfractionated heparin.
AB  - Pregnancy is associated with a physiological increase in coagulation factors and
      heparin binding proteins; both can affect the activated partial thromboplastin
      time (APTT) in response to unfractionated heparin (UFH) invalidating the use of a
      non-pregnant APTT therapeutic range. We compared the anticoagulant response of
      UFH added in vitro to the plasma of 13 pregnant (third trimester) and 15
      nonpregnant women to determine whether the measured APTT and antifactor Xa
      activities are lower in pregnancy. Increasing concentrations of UFH were added to
      platelet-poor plasma from each subject and the APTT and anti-factor Xa activity
      were measured. The amount of UFH which was reversibly bound and neutralised by
      plasma heparin binding proteins was assessed by comparing the anti-factor Xa
      activity before and after addition of low affinity heparin (LAH). Fibrinogen, von
      Willebrand factor antigen (vWF Ag) and factor VIII levels, were also measured.
      The APTT response, assessed by the slope of the regression line of log APTT
      versus added heparin concentration, was attenuated in pregnant plasma (0.76
      s/U/mL versus 1.2 s/U/mL, p = 0.005) and was highly correlated to increased non
      specific plasma protein binding (47% versus 35% p <0.01) and increased fibrinogen
      (5.1 g/L versus 2.8 g/L, p < 0.01) and factor VIII activity (2.7 U/mL versus 1.2
      U/mL, p <0.01). Thus, to achieve the same heparin level, pregnant women require
      higher daily doses of UFH than non-pregnant women. However, if UFH dose
      adjustments during the third trimester are based upon a non-pregnant APTT
      therapeutic range, systematic overdosing of pregnant women will result, possibly
      increasing the risk of bleeding and osteoporosis.

PMID- 11848464
TI  - Plasmin generation plays different roles in the formation and removal of arterial
      and venous thrombus in mice.
AB  - The role of plasminogen (Plg) and alpha2-antiplasmin (alpha2-AP) in vascular
      thrombolysis in vivo was investigated in mice deficient in plasminogen (Plg-/-)
      or a2-AP (alpha2-AP-/-) or their wild type (PAI-1+/+, alpha2-AP+/+). A thrombus
      was induced in the murine carotid artery or the internal jugular vein by
      endothelial injury. Blood flow was continuously monitored for 90 min and for 6 h
      30 min after the initiation of endothelial injury. The times to occlusion by the
      developing thrombus in the carotid artery and the jugular vein of wild type mice
      were 12+/-1.8 and 7.2+/-1.9 min, respectively. The arterial thrombus formation in
      alpha2-AP-/- mice was indistinguishable from the one in wild type mice, whereas
      the time to occlusion in Plg-/- was significantly shortened to 5.9+/-1.7 min.
      Vascular patency after spontaneous reperfusion was markedly improved in alpha2-AP
      /- mice. On the contrary, arteriarpatency in Plg-/- mice was aggravated. In
      venous thrombus formation, the time to occlusion in alpha2-AP-/- mice was
      significantly prolonged (27.1+/-5.2 min), whereas in Plg-/- it was slightly
      shortened to 6.5+/-2.5 min. Vascular patency after spontaneous reperfusion was
      also improved in alpha2-AP-/- mice, but not in Plg-/- mice. Histological
      observations using SEM indicated that fibrin nets were firmly fixed on the
      injured area in Plg-/- mice, but not in alpha2-AP-/- mice. The tail bleeding time
      was not different in any type of mice. However, re-bleeding time using a template
      bleeding device was significantly prolonged in alpha2-AP-/- as compared with that
      of wild type mice. In conclusion, lack of plasminogen markedly reduces the
      antithrombotic activities in vivo, whereas alpha2-AP plays a more important role
      in the formation and removal of venous thrombus in mice. Consequently, the
      inhibition of alpha2-AP could be a useful tool for the therapy of venous
      thrombosis and the prevention of re-thrombus formation.

PMID- 11848465
TI  - Restoration of bax in prostate cancer suppresses tumor growth and augments
      therapeutic cell death induction.
AB  - BACKGROUND: Cancer cells are characterized by multiple genetic defects which
      result in altered rates of cell division, cell death and ability to
      differentiate. These same molecular alterations may also contribute to
      therapeutic resistance. We examined the potential contribution of the pro
      apoptotic gene, bax, to suppressing the growth of prostate cancer cells.
      MATERIALS AND METHODS: The bax-deficient DU145 prostate cancer cell line was
      transfected with a hemagluttinin-tagged bax (HA-bax) vector to generate stable
      expressing bax clones. RESULTS: Ha-bax clones exhibited a significant reduction
      in tumor growth compared to vector control and parental cells when xenografted
      into nude mice. HA-bax clones were significantly more sensitive to cell death
      induction by cis-diamminedichloroplatinum, etoposide, doxorubicin and gamma
      radiation than vector control cells. Sensitivity to paclitaxel remained unaltered
      in the Ha-bax cells. CONCLUSION: These findings suggest that bax may possess a
      tumor suppressor function in prostatic glandular epithelial cells and be an
      important determinant of sensitivity to therapeutic cell death induction.

PMID- 11848466
TI  - Identification and molecular characterization of five novel kallikrein gene 13
      (KLK13; KLK-L4) splice variants: differential expression in the human testis and
      testicular cancer.
AB  - The kallikrein gene family is comprised of genes that have either established or
      potential applications in prostate and breast cancer diagnostics. New members of
      the human kallikrein gene family have been recently identified. By using the
      positional candidate gene approach, we were able to clone a novel human serine
      protease gene that maps to chromosome 19q13.3-q13.4, the location of the
      kallikrein gene family. We named this gene KLK-L4 (now also known as KLK13).
      Here, we describe the identification of five new KLK-L4 splice variants which are
      not expressed in any other tissue except the human testis. We have further
      established that these splice variants can be detected in normal testis but not
      in the adjacent matched testicular tumors. In addition, differential expression
      of the KLK-L4 gene was found in various histological types of testicular cancer.
      Our results suggest that the KLK-L4 gene is expressed in normal and cancerous
      testicular tissue; however, its five variants are all expressed in normal tissue
      but not in testicular tumors. The physiological relevance of these variants and
      the implications of their differential expression between cancerous and normal
      tissues are currently unknown.

PMID- 11848467
TI  - Differential expression of TRAIL-R3 and TRAIL-R4 in human pancreatic cancer.
AB  - BACKGROUND: Pancreatic cancer is one of the most aggressive cancers, in part due
      to its insensitivity to most treatment modalities. This resistance towards
      cytotoxic therapy is thought to be caused--at least in part--by a general
      resistance of pancreatic cancer cells towards apoptosis. TRAIL-R3 and TRAIL-R4,
      which belong to the TRAIL receptor family, can inhibit TRAIL-induced apoptosis.
      PATIENTS AND METHODS: Seven normal pancreatic tissues and 7 pancreatic cancer
      tissues were analyzed using Northern blotting, Western blotting and
      immunohistochemistry. RESULTS: TRAIL-R3 mRNA and protein expression were
      generally weak in pancreatic cancers and normal pancreatic tissues. In contrast,
      TRAIL-R4 mRNA and protein were expressed at moderate to high levels in human
      pancreatic cancer tissues, but demonstrated weak to negative expression in the
      normal pancreas. CONCLUSION: TRAIL-R4 but not TRAIL-R3 levels were significantly
      different in pancreatic cancer in comparison to the normal pancreas. These
      findings give new insight into the resistance mechanisms of pancreatic cancer
      towards TRAIL-mediated apoptosis.

PMID- 11848468
TI  - Inhibition of apoptotic proteins causes multidrug resistance in renal carcinoma
      cells.
AB  - Renal Cell Carcinomas (RCCs) exhibit strong resistance to the most
      chemotherapeutic treatments probably due to the expression of various multidrug
      resistance (MDR) genes. Overexpression of P-glycoprotein (Pgp) is established as
      one such factor, but other mechanisms such as at-MDR, characterized by attenuated
      DNA-topoisomerase II (topoII) activity, may be functional as well. In addition,
      regulating proteins involved in apoptosis can exhibit multidrug resistant
      features. However, prevention of apoptosis as a mechanism of MDR has not yet been
      assessed in RCC, nor has the cytotoxicity of a variety of chemotherapeutic agents
      known to trigger apoptotic or necrotic cell death been tested in RCC in a
      systematic fashion. Using immunohistochemistry and Western blotting, Bcl-2 and
      Bax expression was determined in a panel of multidrug resistant RCC lines
      featuring Pgp and/or at-MDR. The results were related to apoptotic activity and
      kind of cell death in these cell lines, demonstrated by incubation with Hoechst
      33342 and propidium iodide after treatment with various cytotoxic agents and
      quantitated by MTT. In the drug resistant sublines, some decreased Bax and
      strongly increased Bcl-2 expression was seen by immunohistochemistry indicating
      prevention of apoptosis as a distinct feature of MDR in RCC. This was confirmed
      by Western blotting. Sublines revealed significant resistance for all drugs,
      except for CC-313 and DiMIQ. However, these drugs induced necrotic cell death, in
      contrast to all other drugs tested, which induced apoptotic cell death. We
      conclude that, in chemoselected RCC sublines, multidrug resistance appears to be
      functional due to inhibition of apoptosis, apart from the MDR1 and at-MDR
      resistance mechanisms. CC-313 and DiMIQ are very potent cytotoxic agents in RCC,
      probably because they do not kill by induction of apoptosis.

PMID- 11848469
TI  - Chromosome 8 numerical aberration and C-MYC copy number gain in bladder cancer
      are linked to stage and grade.
AB  - Chromosome 8 aberration and c-myc amplification have been suggested as playing
      important roles in the development of different human cancers. Using fluorescence
      in situ hybridization (FISH), chromosome 8 polysomy and c-myc amplification can
      be detected in cells from bladder cancer. We investigated the correlation of
      chromosome 8 polysomy, c-myc gene alteration and p53 deletion with
      histopathological parameters. Twenty-four tumors obtained from patients with
      bladder cancer were analyzed by interphase cytogenetics using FISH with
      chromosome 8 and 17 centromere probes together with an YAC clone covering the c
      myc locus and three cosmid DNA probes covering the p53 locus. Chromosome 8
      polysomy was found in 12 tumors. The average copy number of chromosome 8
      centromere signals were significantly higher in high grade and stage, cancers.
      Also the c-myc copy gain and p53 deletion were significantly correlated with
      grade as well as stage (p<0.05, in both cases). Both polysomy 8 and c-myc copy
      gain were significantly correlated with p53 deletions (p<0.01) and DNA ploidy
      (p<0.001). On the contrary there was no significant correlation between c-myc
      protein over-expression and c-myc gene amplification. These results may indicate
      that alteration of chromosomal regions on 8q and 17p, including c-myc and p53
      genes, may be linked to progression of bladder cancer.

PMID- 11848470
TI  - Antiangiogenic and antitumor effects of a protein kinase Cbeta inhibitor in human
      HT-29 colon carcinoma and human CaKi1 renal cell carcinoma xenografts.
AB  - The compound 317615 x 2HCl, a selective protein kinase Cbeta inhibitor, was not
      very cytotoxic toward human CaKi1 renal cell carcinoma cells or human HT-29 colon
      carcinoma cells in monolayer culture. Isobologram analysis was used to determine
      additivity or synergy of the combination regimens. Exposure of CaKi1 cells to
      317615 x 2HCl (10 or 100 mM) along with gemcitabine or 5-fluorouracil for 24
      hours resulted in cytotoxicity that appeared to be less-than-additive to additive
      for the two agents. Exposure of HT-29 cells to gemcitabine along with 317615 x
      2HCl (10 mM or 100 mM) resulted in a synergistic cytotoxicity while combinations
      with 5-fluorouracil resulted in additive to greater-than-additive cytotoxicity
      for the agents. After treatment of CaKi1 or HT-29 xenograft-bearing mice with
      317615 x 2HCl, immunohistochemical staining for expression of endothelial
      specific markers, either CD31 or CD105, was used to quantify the number of
      intratumoral vessels in the samples. CaKi1 tumor angiogenesis was very responsive
      to treatment with 317615 x 2HCl such that the number of intratumoral vessels
      stained by CD31 or CD105 was decreased to 20% of the control. The HT-29 colon
      carcinoma angiogenesis was also responsive to 317615 x 2HCl, such that the number
      of intratumoral vessels stained by CD31 or CD105 was decreased to 40% to 50% of
      the controL 5-fluorouracil, cisplatin or fractionated radiation therapy was
      combined with treatment with 317615 x 2HCl in the simultaneous combination
      treatment regimen in animals bearing HT-29 colon carcinoma xenografts. The
      resulting tumor growth delays indicated that administration of 317615 x 2HCl
      increased the effects of the cytotoxic therapy. Both a simultaneous or an
      overlapping treatment regimen and a sequential treatment regimen were used to
      assess 317615 x 2HCl alone and along with fractionated radiation therapy or
      gemcitabine against the human CaKi1 renal cell carcinoma xenograft. The CaKi1
      tumor was quite sensitive to fractionated radiation therapy and to gemcitabine
      and, although 317615 x 2HCl was an effective single agent in this tumor, the
      combination regimens did not reach additivity for the combination regimens in
      vivo. 317615 x 2HCl is in early clinical testing.

PMID- 11848471
TI  - Activation of c-MYC and c-MYB proto-oncogenes is associated with decreased
      apoptosis in tumor colon progression.
AB  - BACKGROUND: An increasing amount of evidence suggests that progression from
      normal mucosa to colorectal cancer is accompanied by morphological and genetic
      alterations. Genetic abnormalities affect malignant transformation via a gradual
      imbalance of normal tissue homeostasis involving programmed cell death (PCD) or
      apoptosis. Therefore, it has been hypothesized that alterations in apoptosis may
      contribute to carcinogenesis. The aim of the present work was to investigate the
      relationship between frequency of spontaneous apoptosis during transition adenoma
      to-carcinoma of the colorectal tract and the incidence of activation of c-myc and
      c-myb proto-oncogenes, involved both in colon tumorigenesis and apoptosis.
      MATERIALS AND METHODS: Ninety-five tissue specimens (60 polyps and 35
      adenocarcinomas) were removed with autologous normal adjacent mucosa from colon
      cancer patients. Genomic DNA was extracted and analyzed for both apoptosis
      frequency (DNA fragmentation assay) and proto-oncogene activation (Southern blot
      analysis). On the same samples, Bcl-2 protein expression was evaluated by
      immunohistochemistry. RESULTS: Our results showed that: i) a significant
      relationship exists between apoptosis and genesis of colorectal cancer since,
      compared to adenomatous polyps and adjacent normal mucosa, cell death is markedly
      inhibited in tumors (p = 0.01); ii) during colon tumor progression, apoptosis and
      amplifications of c-myc/c-myb genes are inversely related; iii) Bcl-2 expression
      is retained in colon tumors even though at a significantly lower level with
      respect to adenomatous polyps. CONCLUSION: These results indicate that failure of
      the normal apoptotic process together with de-regulation of c-myc and c-myb proto
      oncogenes might promote the development of colorectal tumors.

PMID- 11848472
TI  - Fas labeling status does not correlate with apoptosis of renal cell carcinoma in
      vivo.
AB  - BACKGROUND: Contribution of the Fas system to apoptosis of renal cell carcinoma
      (RCC) was investigated in vivo. MATERIALS AND METHODS: Tissues from 30 RCC cases
      were immunostained for Fas and Fas ligand (FasL) to assess associations between
      Fas labeling status of RCC, indices of FasL-positive tumor-infiltrating
      mononuclear cells (FasL-TIM) and apoptotic indices (AI) of RCC. RESULTS: In all
      cases, tumor cells co-expressed Fas and FasL; strongly and diffusely in 13 cases
      (43%) and weakly in 17 (57%). Despite the constitutive co-expression of Fas and
      FasL, AI was low in most cases (median, 7 per 1,000 tumor cells; range, 1 to
      257). The Fas labeling status did not significantly associate with AI while FasL
      TIM index positively correlated with AI. CONCLUSION: These results suggest that
      the Fas system is not the principal mechanism of apoptosis of RCC while activated
      tumor-infiltrating mononuclear cells induce apoptosis via mechanisms other than
      the Fas system.

PMID- 11848473
TI  - Characterization of cell lines originating from an invasive transitional cell
      carcinoma.
AB  - A reporter gene (lacZ) was introduced into a human transitional cell cancer cell
      line (Hu1703He) by means of liposomal transfection. The lacZ-transfected cell
      line induced subcutaneous tumours in nude rats and cells from one rat tumour were
      then established as a monolayer culture. The two lacZ-transfected cell lines both
      stained positive for CK7 and negative for CK14 and additionally formed spheroids
      in three-dimensional cultures. Insignificant genomic changes occurred in the
      tumour cells after incubation in nude rats, while the lacZ transfection caused
      alterations that probably correspond to increased invasiveness and
      tumourigenicity in vitro and in vivo. Most important is the observation that lacZ
      transfection of this human TCC cell line does not reduce its invasion potential
      in vitro or in vivo. The lacZ reporter gene may thus be exploited to facilitate
      the identification and quantification of migrating tumour cells and subsequently
      for studies of invasion in in vitro coculture systems. The observation that the
      spheroidal growth is reduced after transfection of the cell line, in contrast to
      increased invasion and cellular growth in monolayer, is an observation indicating
      that a three-dimensional arrangement mimicking the in vivo conditions offers
      important regulating factors to cellular growth.

PMID- 11848474
TI  - Sequence dependence of Alimta (LY231514, MTA) combined with doxorubicin in ZR-75
      1 human breast carcinoma cells.
AB  - Alimta is a new-generation antifolate with inhibitory activity against multiple
      enzymes, including thymidylate synthase, glycinamide ribonucleotide
      formyltransferase and dihydrofolate reductase. Alimta is undergoing broad phase
      II evaluation as a single agent, and preliminary results show responses in
      several tumor types, including breast carcinoma. Doxorubicin is often used in
      combination chemotherapy of breast cancer. Because the two drugs have mechanisms
      of action that might be complementary, we investigated a possible synergism
      between doxorubicin and Alimta on growth inhibition of ZR-75-1 human breast
      carcinoma cells. Cytostatic activity was evaluated using semi-automated MTT
      assays, and drug interactions were determined using CalcuSyn (Chou/Hayball)
      multiple drug effect analyses. The cells were exposed to Alimta or doxorubicin as
      single agents and combinations for 24 hours starting at the time of plating or
      for 72 hours starting 24 hours after plating with a total culture time of 96
      hours. Preincubation with Alimta for 24 hours followed by exposure to doxorubicin
      for 72 hours resulted in highly synergistic activity, whereas the opposite
      sequence or simultaneous exposure produced mainly an additive response. DNA flow
      cytometry studies indicated that Alimta causes a build-up of cells near the G1/S
      interface after 24 hours of incubation. The data suggest that, to obtain maximal
      antitumor activity, Alimta should precede doxorubicin when the drugs are given in
      combination chemotherapy protocols.

PMID- 11848475
TI  - Effects of 17beta-estradiol administration on apoptosis and polyamine content in
      AGS cell line.
AB  - BACKGROUND: Estrogens and polyamines seem to play an important role not only in
      cell growth and differentiation, but also in programmed cell death. The aim of
      the present study was to investigate the effects of 17beta-estradiol
      supplementation on apoptosis as well as on the polyamine content of an ER
      positive human gastric cancer cell line (AGS). MATERIALS AND METHODS: Apoptosis
      was investigated by evaluating DNA fragmentation, using enzyme immunoassay and
      agarose gel electrophoresis and the phosphatidylserine exposure by flow cytometry
      analysis. Polyamine levels were evaluated by HPLC. RESULTS: 17Beta-estradiol gave
      rise to a marked pro-apoptotic effect at concentrations of 16 microM or higher
      compared to the control. Moreover, the hormone significantly reduced the contents
      of polyamines compared to control cells. The apoptotic effect of 17beta-estradiol
      was partially counteracted by exogenous spermine administration. CONCLUSION:
      17Beta-estradiol administration induces apoptosis in AGS cells. Further, an
      increase in cell sensitivity to apoptosis due to a decline in the polyamine
      content may be suggested.

PMID- 11848476
TI  - Transcriptional profiling of cell lines derived from an orthotopic pancreatic
      tumor model reveals metastasis-associated genes.
AB  - In order to identify genes associated with metastasis of ductal pancreatic
      adenocarcinoma we investigated pancreatic tumor cell lines derived from an
      orthotopic pancreatic tumor model in SCID mice. Transcriptional profiling
      (Affymetrix Gene Chip Technology) was performed with cell lines derived from the
      primary tumor and metastatic lesions such as mesentery, liver and lungs. We
      scored for genes commonly deregulated in the cell lines derived from the
      metastatic lesions. Of 7070 genes investigated, 59 (0.83%) were found to be
      deregulated in the cell lines derived from the metastatic lesions. We grouped
      these genes into different categories such as transcription, translation,
      cytoskeleton, cell adhesion, chromosome instability, tumor suppressor genes,
      enzymes and "others". The most remarkable features of the system are the up
      regulation of high mobility group protein HMG-I (Y), twenty-one ribosomal
      proteins, GAPDH and the laminin receptor in the cell lines derived from the
      metastatic lesions, whereas tumor suppressor genes such as maspin and RB1 were
      down-regulated. Inhibition or reconstitution of the activity of these targets are
      an emerging strategy for inhibition of metastasis in this system.

PMID- 11848477
TI  - Modulation of Ki67, p53 and RARbeta expression in normal, premalignant and
      malignant human oral epithelial cells by chemopreventive agents.
AB  - BACKGROUND: Aberrant expression of Ki67, p53 and RARbeta are characteristic of
      many tumor types including those of the oral cavity. Chemopreventive agents may
      act by modulating their expression to more normal levels. MATERIALS AND METHODS:
      The effects of 21 chemopreventive agents on the expression of Ki67, p53 and
      RARbeta were determined using a human in vitro model of normal, premalignant and
      malignant oral epithelial cell lines. RESULTS: Ki67 and mutant p53 (mtp53) were
      overexpressed in both the premalignant and malignant cell lines, whereas
      expression of RARbeta was high in the normal, low in the premalignant and not
      detectable in the malignant cell lines. Most of the agents selectively inhibited
      the expression of Ki67 in the premalignant and malignant cell lines. Eight of the
      21 agents increased, while four agents decreased, the levels of mtp53 protein in
      the premalignant cell line. In the malignant cell line, five of the agents
      increased, while ten agents decreased mtp53 protein levels. The agents increased
      RARbeta expression to near normal levels in the premalignant cell line.
      CONCLUSION: The data suggest that the suppression of Ki67 and mtp53 are good
      indicators of the effectiveness of agents in premalignant and malignant oral
      cells, whereas the enhancement of RARbeta is a measure of effectiveness in
      premalignant oral cells.

PMID- 11848478
TI  - Promyelocytic HL-60 cells induce apoptosis selectively in transformed cells:
      involvement of myeloperoxidase, nitric oxide and target cell-derived superoxide
      anions.
AB  - Promyelocytic HL-60 cells induced apoptosis selectively in transformed
      fibroblasts, but not in nontransformed parental cells or in revertants. Apoptosis
      induction was independent of direct cell-to-cell contact. It depended on the
      number of effector and target cells, pointing to the role of factors derived from
      both cell populations. Inhibitor studies allowed the establishment of the
      following model for intercellular signalling during apoptosis induction: target
      cell-derived superoxide anions spontaneously dismutate and form hydrogen
      peroxide. HL-60 effector cells release MPO which converts hydrogen peroxide into
      hypochlorous acid. Hypochlorous acid then may interact with target-cell-derived
      superoxide anions to yield apoptosis-inducing hydroxyl radicals. In addition,
      effector-cell-derived NO reacts with target-cell-derived superoxide anions and
      forms apoptosis-inducing peroxynitrite. These data explain the selective
      apoptosis induction in transformed cells by effector cells of the granulocyte
      lineage.

PMID- 11848479
TI  - Inhibition of arsenite-induced apoptosis by aspirin.
AB  - Arsenite exposure and subsequent arsenite-induced toxicity and carcinogenesis are
      common in many countries. Thus the study of chemopreventive compounds that
      inhibit arsenite-induced toxicity and carcinogenesis is very valuable. In the
      present work, we investigated the effect of aspirin on arsenite-induced apoptosis
      and signal transduction by means of luciferase activity, apoptosis analysis and
      Western blotting. Arsenite induced AP-1 transcriptional activity at the same
      concentration (20 microM) as was effective for inducing apoptosis. Arsenite
      induced apoptosis and AP-1 transactivation in JB6 cells were blocked by aspirin
      and salicylate (SA). Both aspirin and SA inhibited arsenite-induced
      phosphorylation of Erks, but had no effect on phosphorylation of JNKs. SA
      inhibited arsenite-induced phosphorylation of p38 kinase, but aspirin did not.
      These results indicate that aspirin and SA inhibit arsenite-induced apoptosis
      through the inhibition of the Erks/AP-1 pathway.

PMID- 11848480
TI  - Hypercalcemic-type of small cell carcinoma of the ovary: characterization of a
      new tumor line.
AB  - BACKGROUND: The aim of this study was to develop and characterize a mouse
      xenograft model for the hypercalcemic-type of small cell carcinoma of the ovary
      (HTSCCO). PATIENTS AND METHODS: Tumor fragments were removed from a patient and
      cultured in six subsequent generations of nude mice. Histology, comparative
      genomic hybridization (CGH), electron microscopy and serum calcium levels were
      investigated. RESULTS: Morphology remained the same from the primary tumor of the
      patient through the 6th passage in the mouse. Serum calcium levels were
      significantly higher in the tumor-bearing mice compared to controls. CGH of the
      HTSCCO did not show evidence of a close relationship to either a germ cell tumor
      or an epithelial ovarian cancer. CONCLUSION: Some evidence was provided that the
      HTSCCO is an inhomogeneous tumor that is neither related to a germ cell tumor nor
      to an epithelial ovarian cancer, but is a distinct tumor entity.

PMID- 11848482
TI  - Radio-and chemotoxicity in mice during hypothermia.
AB  - BACKGROUND: The influence of hypothermia induced by chlorpromazine (10-15 mg/kg
      given intra-peritoneally) on the survival from radiation and chemotherapy
      exposure in C57B1-mice, with or without tumour inoculation, was studied.
      MATERIALS AND METHODS: The mice were exposed to either whole body irradiation (8
      Gy), or doxorubicin (15 or 17.5 mg/kg i.p.), or cisplatin (20 mg/kg i. p.) and
      followed to ensuing death. The control mice maintained a rectal temperature of 38
      degres C while those receiving chlorpromazine developed moderate hypothermia of
      28 degrees C or 36 degrees C, dependent on the ambient temperature. RESULTS:
      Hypothermia of 28 degrees C protected the mice from radiation-induced death and
      acute doxorubicin toxicity, with males gaining more protection than females. The
      effects appeared dependent on temperature, not on chlorpromazine. Hypothermia
      protected the mice from acute cisplatin toxicity and increased the anti-tumour
      effects in both genders. Chlorpromazine itself did not cause toxicity, neither
      did it change the natural course of tumour progression. CONCLUSION: Hypothermia
      of 28 degrees C induced by chlorpromazine profoundly reduces radiation,
      doxorubicin-and cisplatin-induced toxicity in mice with males benefiting more
      than females. The hypothermia itself, not the chlorpromazine, was responsible for
      these effects. The anti-neoplastic activity was not compromised; rather, it was
      enhanced, particularly for cisplatin.

PMID- 11848481
TI  - Co-transduction of p27Kip1 strongly augments Fas ligand- and caspase-8-mediated
      apoptosis in U-373MG glioma cells.
AB  - BACKGROUND: p27Kip1 is a potential tumor suppressor gene. As malignant gliomas
      express Fas at high levels, the relationship between Fas-mediated apoptosis and
      p27Kip1 expression may improve therapeutic approaches for treating gliomas.
      MATERIALS AND METHODS: In this study, we transduced U-373MG glioma cells with the
      Fas ligand or caspase-8 genes using adenovirus vectors after transduction of the
      p27Kip1 gene to induce cell cycle arrest in U-373MG cells, and evaluated the
      degree of apoptosis. RESULTS: The results demonstrate that expression of p27Kip1
      enhanced Fas ligand- or caspase-8-mediated apoptosis in U-373MG cells. Expression
      of apoptosis-related genes such as Bax, Bcl-X(L), Bcl-2 or caspase-8 were reduced
      by p27Kip1 transduction compared with that of beta-actin, whereas p27Kip1
      transduction did not affect the expression level of Fas or the Fas ligand.
      CONCLUSION: Combined transduction of p27Kip1 with Fas ligand or caspase-8 would
      overide the resistance mechanism to apoptosis in malignant gliomas.

PMID- 11848484
TI  - Growth stimulation of intestinal tumours in Apc(Min/+) mice by dietary L
      methionine supplementation.
AB  - We studied the effects of extra dietary methionine on the formation and growth of
      intestinal adenomas in the Min (Apc+/-) mouse, which is a murine model of the
      human familial adenomatous syndrome. The AIN-76A diet was supplemented with 0.7%
      L-methionine from week 4 after birth and the animals were killed at week 8. The
      number of tumours in Min mice was apparently not affected by the addition of
      extra methionine. However, the dietary methionine supplementation increased the
      surface area of small intestinal tumours by 41% (p=0.009). In the colon, extra
      methionine did not affect tumour size. In conclusion, extra dietary methionine
      promotes the growth of adenomas in the small intestine of Min mice.

PMID- 11848483
TI  - Hypothermic modulation of doxorubicin, cisplatin and radiation cytotoxicity in
      vitro.
AB  - BACKGROUND: The influence of hypothermia on doxorubicin, cisplatin and radiation
      cytotoxicity was investigated in vitro. MATERIALS AND METHODS: A human glioma
      cell line (251MG) in early exponential growth was exposed to doxorubicin or
      cisplatin at various concentrations for 4 hours, or X-irradiation at 28 degrees C
      or 37 degrees C. The cells continued growing in multi-well plates at 37 degrees C
      and were counted every third day until the end of the logarithmic phase, on day
      13. RESULTS: Exposure to doxorubicin 0.05-0.5 microg/ml or cisplatin 1-10
      microg/ml caused a dose-dependent inhibition of cell growth with a significantly
      reduced toxicity when exposed at 28 degrees C as compared to 37 degrees C.
      Irradiation with 4 Gy also resulted in less toxicity during hypothermia.
      Chlorpromazine 0.01-10 microg/ml, used to induce hypothermia in vivo (1), neither
      influenced, cellular growth itself nor interacted with doxorubicin, cisplatin or
      irradiation. CONCLUSION: Moderate hypothermia (28 degrees C) appears to protect
      against the cellular insult of doxorubicin, cisplatin and ionising irradiation
      and their consequences.

PMID- 11848485
TI  - Down-regulation of IL-18 receptor in cancer patients: its clinical significance.
AB  - Interleukin-18 (IL-18) is a powerful inducer of interferon-gamma (IFN-gamma), a
      key immunoregulatory cytokine. Cellular immune responsiveness, as measured by IL
      18-induced IFN-gamma production from peripheral blood mononuclear cells (PBMCs)
      in ELISA assay, was evaluated in 10 patients with advanced cancer and in 10
      normal controls. Supernatant levels of IFN-gamma were detected at 2 hours after
      PBMCs culture and markedly increased thereafter in healthy volunteers. In
      contrast, IFN-gamma production in cancer patients was not detected during the
      culture period (0-72 hours). We also measured IL-18-stimulated IL-12 production
      in healthy volunteers and null response was observed in cancer-bearing patients.
      Next, we studied mRNA expressions of IL-18 receptor (IL-18R) and IFN-gamma in
      PBMCs in cancer patients and healthy volunteers by RT-PCR assay. Both mRNA levels
      of IL-18R and IFN-gamma were significantly decreased in cancer-bearing patients
      compared with normal controls. These results suggested that IL-18 responsiveness
      for IFN-gamma production in cancer-bearing patients was impaired. Using flow
      cytometric analysis, we studied T-cell subsets, CD3- CD56+ (NK cell), CD3+
      CD45RO+ (memory T-cell), CD3+ CD95+ (Fas+ T-cell), CD3+ CD4+ (helper T-cell),
      CD3+ CD8+ (cytotoxic T-cell: CTL) and CD3+ V alpha24+ (NKT-cell), in cancer
      patients and normal controls. The NK and cytotoxic T-cells significantly
      decreased and NKT-cells had decreased tendency in cancer patients compared with
      normal controls. In contrast, memory T cells, Fas+ T-cells and helper T-cells
      were all significantly increased in cancer patients compared with normal
      controls. These results suggested that the underlying mechanism of impaired IL-18
      responsiveness in PBMCs from cancer-bearing patients was, at least in part,
      ascribed to a drastic decrease of NK cells and CTL which constitutively and
      highly express IL-18R and also attributed to null production of IL-12 which up
      regulates IL-18R.

PMID- 11848486
TI  - Prevention of azoxymethane-induced intestinal tumors by a crude ethyl acetate
      extract and tryptanthrin extracted from Polygonum tinctorium Lour.
AB  - The effect of a crude ethyl acetate (AcOEt)-extract and tryptanthrin extracted
      from the Indigo plant (Polygonum tinctorium Lour.) on azoxymethane (AOM)-induced
      intestinal tumors was examined in F344 rats. The rats were given subcutaneous
      (s.c.) injections of either AOM (15 mg/kg body weight (b.w.)) once a week for 3
      weeks to induce atypical crypt foci (ACF) as a known cancer precursor, or AOM
      (7.5 mg/kg b.w.) once a week for 10 weeks to induce intestinal tumors. The rats
      were also administered the AcOEt-extract (500 mg/kg b.w.) or tryptanthrin (50
      mg/kg b.w.) orally, 5 days a week, for 7 or 30 weeks, starting two days before
      the first administration of AOM. All rats were killed 4 or 20 weeks after the
      last treatment. In the short-term experiment, the incidence of ACE and atypical
      crypts (AC) in the groups receiving the AcOEt-extract and tryptanthrin was
      significantly lower than in the control group. In the tumor-inducing experiment,
      intestinal tumor incidence in the tryptanthrin group was lower than in the AOM
      control group (5% versus 26%), and small intestine tumor incidence in the AcOEt
      extract and tryptanthrin groups were lower than in the AOM-control group (0% and
      0% versus 23%). These results show that the AcOEt-extract of Indigo and
      tryptanthrin have cancer chemopreventive activity.

PMID- 11848487
TI  - Effects of interferon-beta in combination with 5-fluorouracil on the growth of
      esophageal cancer cells in vitro.
AB  - The possible antiproliferative potency of human recombinant interferon-beta (hIFN
      beta) towards ten human esophageal cancer cell lines was examined in comparison
      with the activity of the factor towards human malignant melanoma cell lines. The
      cell growth of esophageal cancer cell lines was inhibited by hIFN-beta in a dose-
      and time- dependent manner. The 50% inhibitory concentrations (IC50) of hIFN-beta
      on nine cell lines out of ten ranged between 23 to 332 IU/ml of culture medium.
      The remaining cell line, T.Tn, was less sensitive to the interferon (IC50, 611
      IU/ml). Under the same culture conditions, the melanoma cell lines tested
      differed markedly in their sensitivity to hIFN-beta. When the esophageal cancer
      cells were treated with 5-fluorouracil (5-FU) in the presence of a low
      concentration of hIFN-beta, the effectiveness of 5-FU was markedly enhanced. In
      particular, the rate of growth inhibition of T.Tn cells was more than the added
      potencies of 5-FU and hIFN-beta indicating that the interferon is an effective
      biomodulator of 5-FU. All these data suggest that combination therapy with hIFN
      beta and the anticancer drug 5-FU would be beneficial for the treatment of
      carcinoma of the esophagus.

PMID- 11848488
TI  - BRCA1 germline mutations in Cypriot breast cancer patients from 26 families with
      family history.
AB  - Germline mutations in the BRCA1 gene are causative for a variable number of
      hereditary breast/ovarian cancers. The data presented in this study are based on
      genetic analysis of the BRCA1 gene in 49 DNA samples from breast cancer patients
      with a positive family history. A combination of manual direct DNA sequencing and
      SSCP analysis was used to screen the entire coding region of BRCA1. Overall 13
      variants were detected which included 5 missense mutations, 3 polymorphisms and 5
      intronic changes. Further genetic analysis of the 13 variants was carried out
      using 50 control DNA samples. Our results showed that 12 out of the 13 variants
      detected in the DNA of the patients group, were also present in the control
      group. It appears that the Greek Cypriot families studied so far have an
      unexpectebly low frequency of deleterious mutations in the BRCA1 gene. This is
      the first report on BRCA1 mutation analysis in Cyprus.

PMID- 11848489
TI  - Improved safety, pharmacokinetics and therapeutic efficacy profiles of a novel
      liposomal formulation of mitoxantrone.
AB  - We describe here the preclinical studies of a novel formulation of liposome
      entrapped mitoxantrone (LEM). The liposome entrapment efficiency of mitoxantrone
      was 93.4 +/- 2.8%. In vitro cytotoxicity studies in HL60 cells comparing LEM with
      conventional mitoxantrone (MTO) showed IC50 values of 0.31 +/- 0.05 ng/ml and
      0.48 +/- 0.06 ng/ml for LEM and MTO, respectively. In CD2F1 mice, LEM was
      significantly less toxic as compared with MTO. A single intravenous (i.v.) dose
      of 15 mg/kg MTO produced 100% mortality in CD2F1 mice by Day 10, whereas a single
      i.v. dose as high as 35 mg/kg LEM caused no mortality for at least up to Day 60
      post-treatment. Multiple doses of MTO (i.v., 5.0 mg/kg, 1x daily, x5) caused 100%
      mortality by Day 10, whereas a similar dose regimen of LEM caused no mortality in
      CD2F1 mice. Clinical and histopathology evaluations indicated long-term normal
      tissue protection in mice treated with relatively high single dose (i.v., 35
      mg/kg) or multiple doses of LEM (i.v., 5.0 mg/kg, 1x daily, x5). LEM also
      demonstrated favourable pharmacokinetic profiles. CD2F1 mice injected with 5
      mg/kg i.v. dose of LEM showed plasma levels 51-fold higher than with an
      equivalent dose of MTO. The area under the plasma concentration-time curve was
      200-fold greater with LEM as compared to MTO. The plasma half-lives were 0.96
      hours and 0.11 hours for LEM and MTO, respectively. An altered tissue
      distribution was observed with LEM; cardiac tissue demonstrating at least 2.6
      fold lower levels of mitoxantrone with LEM vs. MTO. LEM exhibited significant
      anti-tumor activity against murine ascitic L1210 leukemia in CD2F1 mice.
      Treatment with a single dose of 20.0 mg/kg LEM resulted in 100% long-term
      survivors. LEM 2.5 mg/kg (i.v., x4) had antitumor activity against a human
      hormone-independent prostate carcinoma (PC-3) grown in athymic mice, while a
      comparable dose of MTO was too toxic. A significant decrease in toxicity, altered
      pharmacokinetics, and enhanced efficacy of LEM suggest that LEM may provide a
      viable alternative to the clinical use of conventional mitoxantrone.

PMID- 11848490
TI  - Expression of nitrotyrosine is associated with angiogenesis in esophageal
      squamous cell carcinoma.
AB  - BACKGROUND: In our previous study, it was suggested that nitrotyrosine, a product
      of nitrogen species, found in esophageal squamous cell carcinoma (ESCC), may
      contribute to the progression of esophageal cancer. MATERIALS AND METHODS: To
      clarify whether nitrotyrosine expression is associated with apoptosis and/or
      angiogenic factors in ESCC, we have analyzed the relationship between
      nitrotyrosine presence and the apoptosis-related proteins, Bcl-2 and Bax, or
      CD34, the marker of vascular endothelial cells, by an immunohistochemical
      approach. RESULTS: Nitrotyrosine was detected in 21 out of 55 esophageal cancers.
      The correlation between nitrotyrosine presence and Bcl-2, Bax expression or
      apoptotic index (AI) was not significant. In contrast, nitrotyrosine presence was
      significantly correlated with the microvessel density (MVD); nitrotyrosine
      positive specimens tended to show a high MAD, while nitrotyrosine-negative
      specimens tended to be associated with a low MVD (p<0.05). CONCLUSION: Our data
      suggest that NO induces progression of esophageal carcinoma through its effect on
      angiogenesis, rather than its effect on tumor apoptosis.

PMID- 11848491
TI  - Antioxidative activity of Allium victorialis L. extracts.
AB  - Allium victorialis L. (Liliaceae, "Hon-Gyoujya Nin-Niku" in Japanese) was
      successively extracted with hexane, acetone, methanol and 70% methanol and the
      extracts were further separated into a total of twenty-five fractions by silica
      gel and ODS column chromatographies. The biological activities of these four
      extracts and 25 column fractions were compared. The cytotoxic activity of all
      extracts and fractions against two oral tumor cell lines was significantly higher
      than that against normal human gingival fibroblasts, suggesting their tumor
      specific action. Three methanol column fractions [M2, M3, M6] and a 70% methanol
      column fraction [70M6] most effectively reversed the multidrug resistance (MDR)
      against L5178 mouse T cell lymphoma. The electron spin resonance (ESR)
      spectroscopy showed that methanol column fractions and 70% methanol extracts
      produced the highest amount of radical(s) and most efficiently scavenging O2*-,
      generated by the hypoxanthine-xanthine reaction system, suggesting that the same
      substances in these fractions display both prooxidant and antioxidant properties.
      They showed no anti-human immunodeficiency virus (HIV) or anti-Helicobacterpylori
      activity. These data suggest the medicinal efficacy of Allium victorialis
      extract.

PMID- 11848492
TI  - Heat shock protein 70 (HSP70) does not prevent the inhibition of cell growth in
      DU-145 cells treated with TGF-beta1.
AB  - BACKGROUND: Mitogen-activated protein kinase (MAPK) is one of the transforming
      growth factor-beta (TGF-beta signaling pathways while heat shock protein 70
      (HSP70) prevents apoptosis by affecting MAPK signaling downstream. However, the
      interrelationship between TGF-beta and HSP70 signaling is still unknown.
      MATERIALS AND METHODS: DU-145 prostate cancer cells were treated with 40 pM and
      200 pM TGF-beta1. After 3, 6, 9, 12 and 24 hours, cell proliferation assay and
      cell cycle analysis were performed. The activities of HSP70 and MAPKs (c-Jun N
      terminal kinase 1 (JNK1), extracellular signal-regulated kinase 1 (ERK1), ERK2
      and p38) were analyzed by Western blot at each time-point. RESULTS: TGF-beta1
      inhibited the cell growth in a dose-dependent manner at 3 hours. Late G1
      accumulation in the cell cycle was observed in a dose-dependent manner after 24
      hours. HSP70 and JNK1 increased only at 3 hours and decreased for up to 24 hours
      thereafter. ERK1, ERK2 and p38 decreased from 3 to 24 hours after TGF-beta1
      treatment. CONCLUSION: These data suggest that HSP70 does not prevent the
      inhibition of cell growth in DU-145 cells treated with TGF-beta1.

PMID- 11848494
TI  - Effects of 1,25(OH)2D3, EB1089, and analog V on PTHrP production, PTHrP mRNA
      expression and cell growth in SCC 2/88.
AB  - BACKGROUND: We investigated the effects of 1,25(OH)2D3 and selected analogs on
      canine squamous carcinoma cells (SCC 2/88) and tested whether these compounds
      could effectively decrease proliferation, induce differentiation, and inhibit
      PTHrP production and PTHrP mRNA expression. MATERIALS AND METHODS: SCC 2/88 cells
      were cultured and treated with three substrates. The media were collected for
      PTHrP immunoradiometric assay. The cells were analyzed for DNA concentration and
      PTHrP mRNA expression by Northern blot analysis, involucrin by Western blot
      analysis and 1,25(OH)2D3-receptor (VDR) and PTHrP by immunohistochemistry.
      RESULTS: The SCC 2/88 cells were stained positively for VDR and PTHrP by
      immunohistochemistry. 1,25(OH)2D3 and its analogs inhibited cell growth and
      stimulated differentiation in a dose-dependent manner. All three substrate
      treated groups had significantly increased PTHrP secretion at 10(-7) M. Cells
      treated with 1,25(OH)2D3 at 10(-7) M had 2- to 4-fold increased PTHrP mRNA
      expression at 12 and 24 hours compared to the vehicle-treated controL PTHrP mRNA
      in cells treated with TGF-beta (1.5 ng/ml) was increased 7- to 17-fold at 6, 12
      and 24 hours compared to the vehicle-treated controL PTHrP mRNA expression was
      reduced by 0.5- to 2-fold in cells treated with 1,25(OH)2D3 at 10(-7) M and TGF
      beta (1.5 ng/ml) together compared to cells treated with TGF-beta alone.
      CONCLUSION: 1,25(OH)2D3, EB1089, and analog V inhibited SCC 2/88 growth and
      induced differentiation in a dose-dependent manner, but did not inhibit PTHrP
      production. 1,25(OH)2D3 treatment led to increased PTHrP mRNA expression and
      reduced the stimulatory effect of TGF-beta on PTHrP mRNA expression in SCC 2/88
      cells.

PMID- 11848493
TI  - Inhibition of chlorogenic acid-induced cytotoxicity by CoCl2.
AB  - Chlorogenic acid (CGA) induced apoptotic cell death in human oral squamous cell
      carcinoma (HSC-2) and salivary gland tumor (HSG) cell lines. CGA exhibited
      oxidation potential in the culture medium, as demonstrated by NO monitor. Both
      cytotoxic activity and oxidation potential were significantly reduced by the
      addition of CoCl2. ESR spectroscopy showed that CGA produced seven peaks of
      radicals under alkaline condition, while addition of CoCl2 altered the spectral
      pattern and diminished the radical intensity of CGA. CoCl2 accelerated the CGA
      induced coloration of the culture medium and modified the difference spectrum at
      around 325 nm, an absorption maximum characteristic of CGA. These data suggest
      that CoCl2 induced conformational changes in the CGA molecule.

PMID- 11848495
TI  - Heparanase gene expression and metastatic potential in human gastric cancer.
AB  - BACKGROUND: Heparanase has been reported to play an important role in tumor
      progression and metastasis. We examined the relationship between heparanase mRNA
      expression and biological factors regarding invasion and metastasis of human
      gastric cancer. MATERIALS AND METHODS: In 63 human gastric carcinomas, 42
      adjacent normal gastric tissues and four gastric cancer cell lines, heparanase
      mRNA expression was evaluated using reverse transcription PCR (RT-PCR). Total RNA
      obtained from human peripheral blood (PB) leucocyte and placenta were used as
      positive controls. The relationship between heparanase mRNA expression and
      various clinicopathological factors were analyzed. RESULTS: The heparanase mRNA
      expression evaluated with RT-PCR revealed that 31 out of 63 gastric cancer
      tissues (49%), 11 out of 42 normal gastric tissues (26%) and 4 gastric cancer
      cell lines were positive. The positive rate in cancer tissues was significantly
      higher than that in normal tissues (p<0.05). In the heparanase mRNA-positive
      cancer tissues, venous invasion was frequent (p<0.05) and the histological
      differential grade was significantly poorer than in negative cases (p<0.01).
      CONCLUSION: We propose that heparanase mRNA expression is involved in invasion
      and development of human gastric cancer and detection of this expression may be a
      factor related to metastasis and prognosis of such patients.

PMID- 11848496
TI  - Cytotoxic activity of 2-aminomethylene-3(2H)-benzofuranones against human oral
      tumor cell lines.
AB  - A total of 23 newly-synthesized 2-aminomethylene-3(2H)-benzofuranone and
      structurally-related compounds were compared for their cytotoxic activity against
      both normal (human gingival fibroblast HGF) and tumor cells (human oral squamous
      cell lines HSC-2, HSC-3 and human salivary gland tumor cells HSG). There was a
      significant variability of drug sensitivity among the oral tumor cell lines. In
      general, HSC-2 cells were the most sensitive, followed by HSG cells, while HSC-3
      cells were the most resistant. HGF normal cells were highly resistant to all
      compounds, suggesting their tumor-specific cytotoxic action. The cytotoxic
      activity of the compounds with morpholine, 1-methylpiperazine or piperidine
      structure was generally elevated by the introduction of fluorine, but not
      chlorine and methoxy functional groups, to the benzofuranone structure, whereas
      that of compounds attached by 1-phenylpiperazine or 1-(2-pyridyl)piperazine was
      rather reduced. The most active compounds induced internucleosomal DNA
      fragmentation in human promyelocytic leukemia HL-60 cells, but not in HSG,
      further confirming that oral tumor cell lines are resistant to DNase digestion.

PMID- 11848497
TI  - Changes in expression of onco- and suppressor genes in peripheral leukocytes--as
      potential biomarkers of chemical carcinogenesis.
AB  - An animal model was developed to investigate the expression of two oncogenes (c
      myc, Ha-ras) and a suppressor gene (p53) as early markers of the effects of
      carcinogenic exposure and/or tumourigenesis. Inbred Long-Evans rats were treated
      with 7,12-dimethylbenz(a)anthracene and the transient/permanent gene expressions
      were measured after 24 and 48 hours by dot blotting in potential target tissues
      (lung, liver, lymph nodes, kidneys, spleen) and in peripheral blood leukocytes.
      The aim of the study was to test blood leukocytes, as surrogate tissue, showed
      similar expression patterns of the selected genes following carcinogenic
      exposure. c-myc did not prove to be an applicable early biomarker due to the lack
      of or low level of its expression. However, remarkable of early elevations were
      detected in the expression signals of Ha-ras and p53.

PMID- 11848498
TI  - Lipolytic and lipoprotein lipase (LPL)-inhibiting activities produced by a human
      lung cancer cell line responsible for cachexia induction.
AB  - Previous studies have shown that five human cancer cell lines, LS180, MKN-1, MMG
      1, C32 and LX-1, induced remarkable weight loss in tumor-bearing nude mice. With
      the aim of identifying novel molecules involved in lipid catabolism, conditioned
      media of these cancer cell lines were analyzed in terms of lipoprotein lipase
      (LPL)-inhibiting or lipolytic activities. All conditioned media from the five
      cell lines significantly suppressed LPL activity in 3T3-L1 cells, while media
      from LX-1 and C32 promoted lipolytic activity in a dose-dependent manner. RT-PCR
      and ELISA demonstrated that the major factors responsible for LPL inhibition and
      lipolysis were not IL-1beta, IL-6, IL-11, TNF-alpha, TGF-beta1 or LIF in all the
      cancer cell lines except for MMG-1 cells. Preliminary biochemical analysis showed
      that the LPL-inhibiting factor produced by LX-1 cells was approximately 65 kD and
      vulnerable to heat, whereas the lipolytic factor was less than 1 kD and heat
      stable. These results suggested that unknown factors are partially involved in
      the pathogenesis of cancer cachexia in tumor-bearing nude mice and further
      purification will be needed.

PMID- 11848500
TI  - Characterisation of taurine uptake in human KB MDR and non-MDR tumour cell lines
      in culture.
AB  - Studies on taurine transport in MDR (multidrug resistant) and non-MDR KB cancer
      cells show that both cell types contain Na(+)- and Cl(-)-dependent high-affinity
      and low-affinity transport systems selective for beta-amino acids and a taurine
      diffusion component. Good buffers, such as HEPES or MOPS, interfered with taurine
      uptake. The basal taurine Vmax measured in isoosmotic medium represented 1/5 of
      taurine captured by uptake in KB non-MDR, but was negligible in KB MDR cells.
      High-and low- affinity uptake systems were reduced by medium hyperosmolarity in
      both cell types. Although properties of low-and high-affinity transport systems
      were similar in both cell types, Vmax (but not Km) were reduced in MDR compared
      to non-MDR cells. Taurine uptake was unaffected by chemotherapeutic agents
      (doxorubicin, vinblastine) or MDR revertants (verapamil). Taurine did not affect
      cell proliferation of MDR or non-MDR cells nor did it alter the inhibitory effect
      of doxorubicin or vinblastine cell proliferation.

PMID- 11848499
TI  - Erucylphosphocholine-induced apoptosis in chemoresistant glioblastoma cell lines:
      involvement of caspase activation and mitochondrial alterations.
AB  - Intrinsic chemoresistance constitutes a major problem in the therapy of malignant
      gliomas. In vitro experiments with four astrocytoma/glioblastoma (AC/GBM) cell
      lines revealed that the chemoresistance of two cell lines, A172 and T98G, to
      cisplatin and etoposide was due to resistance to drug-induced apoptosis. In
      contrast, all the AC/GBM cell lines tested were sensitive to treatment with the
      lipophilic ether lipid erucylphosphocholine, ErPC. ErPC-induced apoptosis was
      independent of wild-type p53-signaling and triggering of the CD95/CD95 ligand
      (CD95L) system. Inhibition of protein and RNA synthesis by cycloheximide and
      actinomycin D did not abrogate ErPC-induced apoptosis. However, expression of
      members of the bcl-2 protein family was modulated during ErPC treatment.
      Activation of caspase 3 and mitochondrial alterations were central to ErPC
      induced apoptosis. We conclude that ErPC-induced activation of the mitochondrial
      pathway enables cell death in the chemoresistant AC/GBM cells.

PMID- 11848501
TI  - Chemopreventive effects of curcumin on glandular stomach carcinogenesis induced
      by N-methyl-N'-nitro-N-nitrosoguanidine and sodium chloride in rats.
AB  - The modifying effects of pure curcumin on glandular stomach carcinogenesis were
      investigated during the post-initiation phase in male Wistar rats treated with N
      methyl-N'-nitro-N-nitrosoguanisine (MNNG) and sodium chloride. A total of 110
      male 6-week-old rats were divided into four groups. Groups 1-3 (consisting of 30
      rats/group) were given MNNG in their drinking water at a concentration of 100 ppm
      and simultaneously fed a diet supplemented with 5% NaCl for 8 weeks. They were
      then fed a diet containing either 0.2% (group 1) or 0.05% (group 2) pure curcumin
      or kept on a basal diet alone (group 3) for 55 weeks. The rats of the curcumin
      treated groups (groups 1 and 2) were then switched to the basal diet for the
      following 4 weeks before sacrifice. Group 4 (20 rats) served as a non-treatment
      control. The total incidence of combined atypical hyperplasias and
      adenocarcinomas in the glandular stomachs was rather lower in groups 1 (93%) and
      2 (90%) than in group 3 (100%), albeit without statistical significance. However,
      the mean number of atypical hyperplasias or adenocarcinomas of the glandular
      stomachs in group 1 (4.70) was significantly less than the value of group 3
      (7.17) (p<0.05). Thus, the development of cancerous and precancerous lesions in
      the glandular stomach was decreased by exposure to pure curcumin. The present
      results indicate that the compound exerts chemopreventive effects, when given
      during the post-initiation phase of glandular stomach carcinogenesis in rats.

PMID- 11848502
TI  - Variations of EGF-R surface expression in squamous cell carcinomas of the head
      and neck region.
AB  - BACKGROUND: It has been previously found that the epidermal growth factor
      receptor (EGF-R) is highly expressed in squamous cell carcinomas of the head and
      neck region (SCCHN) and that this expression correlates with malignant
      transformation and tumor development. MATERIALS AND METHODS: We examined 9 SCCHN
      cell lines and a control keratinocyte cell line for EGF-R expression, utilizing
      fluorescence-activated cell sorting (FACS) and Western blot analysis. Immuno
      cytochemistry was performed to evaluate the receptor's cellular distribution.
      RESULTS: We found the EGF-R to be up-regulated in SCCHN. Surprisingly we did not
      see a clear correlation between tumor staging, grading or Stat3 signaling and EGF
      R level but we observed up to three distinct EGF-R specific bands in our Western
      blots, implicating the presence of different protein isoforms. CONCLUSION: Our
      data suggest that not only the amount but also the receptor function, including
      the presence of mutations, need to be considered in SCCHN malignancies.

PMID- 11848503
TI  - Inflammatory stromal reaction correlates with lymphatic microvessel density in
      early-stage cervival cancer.
AB  - BACKGROUND: In early-stage cervical cancer, high lymphatic microvessel density
      (LMVD) indicates favorable prognosis. This unexpected finding was thought to be
      an effect of local immunological response, although no data supported this
      thesis. MATERIALS AND METHODS: LMVD and lymphovascular invasion (LVI) were
      assessed in 85 specimens of cervical cancer stage pT1b by immunostaining for
      podoplanin, a marker for lymphatic endothelia. Local immunological response,
      evident by inflammatory stromal reaction (ISR), was determined in H&E-stained
      slides and rated from grade 1 (absent or weak) to 3 (strong) RESULTS: A good
      correlation of LMVD and ISR was found (p=0.002). While a strong correlation
      between LMVD and the presence of LVI was found (p<0.001), no association between
      LMVD and pelvic lymph node involvement (p=0.732) was observed. ISR indicated
      favourable prognosis of patients (p=0.0247, log-rank test). CONCLUSION: Our
      findings suggest that ISR might play a role in the induction of lymphangiogenesis
      in early stage cervical cancer.

PMID- 11848504
TI  - Dose-response effects of the COX-2 inhibitor, celecoxib, on the chemoprevention
      of mammary carcinogenesis.
AB  - Recent chemopreventive studies in our laboratories showed that the COX-2
      inhibitor, celecoxib, inhibited the induction of mammary cancer by 7,12
      dimethylbenz(a)anthracene (DMBA). In this study, we examined the relative
      chemopreventive effect of varying doses of celecoxib on the development and
      growth of DMBA-induced rat mammary tumors. At 10 days prior to receiving a single
      intragastric dose of 15 mg DMBA/rat, female Sprague-Dawley rats were fed a
      control chow diet or diets containing 250, 500, 1000 or 1500 ppm celecoxib until
      termination of the experiment. Administration of increasing doses of celecoxib
      inhibited mammary tumor incidence and multiplicity as well as tumor volume in a
      dose-dependent manner. At 122 days post DMBA-intubation, mammary tumor incidence
      was 100% in the control rats compared to 80%, 50%, 45% and 25% in rats receiving
      250, 500, 1000 or 1500 ppm celecoxib, respectively (p<0.001). Similarly, tumor
      multiplicity and tumor volume were significantly reduced by increasing the dose
      of celecoxib from 250 to 1500 ppm in the diet. The control rats had an average of
      3.46 tumors/rat compared to 1.80, 1.00, 0.75 and 0.50 tumors/rat in animals
      receiving 250, 500, 1000 or 1500 ppm celecoxib, respectively (p<0.001). Average
      tumor volumes in rats fed 250, 500, 1000 or 1500 ppm celecoxib were 0.42, 0.34,
      0.31 and 0.16 cm3 compared to 1.29 cm3 in the control rats (p<0.001). There was a
      concomitant increase in the steady-state serum concentration of celecoxib with
      the dose. These results indicate that, in this rat model, the chemopreventive
      effect of celecoxib against breast cancer is dose-dependent and that celecoxib is
      effective even at lower dose levels.

PMID- 11848505
TI  - Potential usefulness of 99mTc-labeled monoclonal antibody A7 for
      immunoscintigraphy of human pancreatic carcinoma.
AB  - BACKGROUND: To improve survival rates of patients with pancreatic carcinoma, it
      is critical to develop new technology for early and certain diagnosis. One
      possibility is the application of radioimmunoscintigraphy using radiolabeled
      monoclonal antibodies. MATERIALS AND METHODS: Monoclonal antibody A7 (Mab A7) was
      labeled with technetium-99m (99mTc) and injected into athymic nude mice bearing
      human pancreatic carcinoma xenografts in order to examine its usefulness for
      radioimmunoscintigraphy. RESULTS: The binding activity of 99mTc labeled Mab A7
      was nearly identical to that of non-labeled Mab A7. When 99mTc-labeled Mab A7 was
      injected intravenously into tumor-bearing nude mice, tumor accumulation of 99mTc
      labeled Mab A7 increased until 24 hours after injection and then decreased
      slowly. The tumor tissue/blood ratio of radioactivity was significantly greater
      than that of normal mouse IgG. CONCLUSION: These results suggest that 99mTc
      labeled Mab A7 is suitable for radioimmunoscintigraphy of human pancreatic
      carcinoma.

PMID- 11848506
TI  - Synergistic cytotoxic action of vitamin C and vitamin K3.
AB  - We investigated the combination effect of sodium ascorbate (vitamin C) and
      menadione (vitamin K3) on the viability of various cultured cells. Human oral
      squamous cell carcinoma (HSC-2, HSC-3) and human promyelocytic leukemia (HL-60)
      cells were more sensitive to these vitamins as compared to normal cells (human
      gingival fibroblast HGF, human periodontal ligament fibroblast HPLF, human pulp
      cell HPC). The combination of vitamin C and vitamin K3 produced synergistic
      cytotoxicity against all these 6 cell lines. Treatment with vitamin C or vitamin
      K3, or their combination, induced internucleosomal DNA fragmentation only in HL
      60 cells, but not in the oral tumor cell lines (HSC-2, HSC-3, HSG). ESR
      spectroscopy showed that vitamins C and K3 produce radicals under alkaline
      conditions and that the combination of these two vitamins synergistically
      enhanced their respective radical intensities.

PMID- 11848507
TI  - Inhibition of tumor cell growth by Schiff bases of hydroxysemicarbazide.
AB  - The inhibitory activities of Schiff bases of hydroxysemicarbazide (HSC) against
      eight human and murine tumor cell lines and one non-cancer cell line were studied
      using MTS/PES microculture tetrazolium and methylene blue assays. Compounds 1 (1
      [9-(10-methylanthryl)methylene]-4-HSC), 2 (1-[2-hydroxy-3,5-dibromobenzylidene]-4
      HSC) and 3 (1-[2,3,4-trihydroxybenzylidene]-4-HSC), which have been shown to be
      active against murine leukemia L1210 cells in our laboratories, inhibited human
      leukemia CCRF-CEM cells with similar IC50s ranging from 2.7 to 7.0 microM. Of the
      compounds tested against attached tumor cell lines (B16, CHO, HT29, ZR75) at 50
      microM concentration, compound 1 showed the strongest inhibition, followed by 4
      (1-[2-(5-nitrothienyl)methylene]-4-HSC), 2 and 5 (1-[2-hydroxy-3,5
      diiodobenzylidene]-4-HSC) with more than 50% inhibition. The IC50s of compound 1
      were found to range from 2.7 to 12 microM against the attached tumor cell lines
      examined. As compared with hydroxyurea, compound 1 had more favorable selectivity
      against tumor cells. Further more, compound 1 was found to have IC50s of 2.8 and
      6.5 microM against hydroxyurea-resistant and gemcitabine-resistant KB cells,
      respectively, but had no cross-resistance with hydroxyurea and gemcitabine (two
      known ribonucleotide reductase inhibitors acting at different sites of the same
      enzyme). In conclusion, several Schiff bases of HSC showed inhibition of tumor
      cell growth at micromolar concentration and had no cross-resistance with
      hydroxyurea-resistant KB cells.

PMID- 11848508
TI  - Lectin (WGA)-dependent superoxide anion release by neutrophils as a prognostic
      factor in lung cancer.
AB  - This study was performed to explore whether lectin-induced generation of
      superoxide anions by neutrophils, lectin-induced degranulation of these cells and
      NO-synthase activity in pleural effusions can be used as prognostic factors of
      primary lung cancer patients. Among the activities tested, increased generation
      of superoxide by Triticum vulgaris agglutinin (WGA)-activated neutrophils showed
      prognostic relevance. Thus, this lectin-dependent reactivity of immune cells
      warrants further investigation in addition to the histochemical analysis.

PMID- 11848509
TI  - A re-evaluation of fumagillin selectivity towards endothelial cells.
AB  - We have re-evaluated the selectivity of fumagillin against endothelial cell
      proliferation and compared it to the reported selectivity of its potent analog
      TNP-470. We showed that fumagillin does not inhibit endothelial cell
      proliferation in a specific manner, but on the contrary it inhibits the
      proliferation of other cell types at the same range of concentrations.
      Furthermore, the IC50 values of fumagillin for endothelial cells are two orders
      of magnitude higher than those values reported for TNP-470 on endothelial cells;
      on the contrary, the IC50 value of fumagillin for human breast cancer MDA-MB231
      cells is four orders of magnitude lower than the value reported for TNP-470 on
      the same cell line.

PMID- 11848510
TI  - GSTM1, P53 and K-ras molecular detection in resectable non-small cell lung cancer
      by denaturing gradient gel electrophoresis-bronchoalveolar lavage fluid analysis.
AB  - BACKGROUND: Understanding molecular abnormalities could potentially lead to novel
      investigational approaches in the molecular epidemiology of lung cancer. These
      might include the identification of patients at high risk for primary NSCLC and
      the surveillance of patients with known NSCLC who are being treated using lung
      sparing surgical strategies. MATERIALS AND METHODS: The PCR-Denaturing Gradient
      Gel Electrophoresis (DGGE) strategy was used for primary tumors and corresponding
      bronchalveolare lavage (BAL) samples. RESULTS: We recruited 36 consecutive
      patients with NSCLC, 28 (77.7%) males and 8 females (22.3%). DGGE showed a good
      rate of accuracy in the genetic screening of K-ras and p53 mutations in BAL
      specimens. Specific mutations were more often detected in BAL fluid from patients
      with not peripheral tumors than parenchymal or peripheral tumors (p53: 85.7%,
      p=0.0004; K-ras: 75%, p=0.001). p53 mutations were more frequent in BAL fluid
      from squamous cell carcinomas (22%) than from adenocarcinomas (15%). A
      significant correlation was observed between null GST-Ml genotype and p53 overall
      mutations (p=0.0003), K-ras mutations (p=0.02), non peripheral tumors (p=0.04)
      and smoking habits (p=0.002). CONCLUSIONS: We observed that null GSTMl genotype
      is strongly related to p53 mutations. Individuals at high risk for primary NSCLC,
      such as heavy smokers or individuals exposed to occupational carcinogens, could
      be screened by BAL-analysis for cancer biomarkers of susceptibility like GSTM-1
      in large scale molecular epidemiology studies.

PMID- 11848511
TI  - KDR promoter can transcriptionally target cytosine deaminase suicide gene to
      cancer cells of nonendothelial origin.
AB  - The KDR/flk-1 gene promoter is considered to be endothelial cell-specific. We
      show its activity in two cancer cell lines of non-endothelial origin: in murine
      L1 sarcoma and OVP-10 human ovarian carcinoma cell lines. KDR promoter-driven
      cytosine deaminase gene can be efficiently expressed in these cells leading to
      sensitization to 5-fluorocytosine, as demonstrated both in vitro and in vivo. Our
      results indicated that KDR promoter activity is not endothelial cell-exclusive
      and that this promoter can also be used to obtain specific expression of
      therapeutic genes in certain cancer cells.

PMID- 11848512
TI  - Early macrophage and cytokine response during the growth of immunogenic and non
      immunogenic murine tumors.
AB  - Very little data exist on the mechanisms of innate immunity during the first days
      after syngeneic tumor inoculation. Nonspecific macrophage reaction precedes the
      development of specific immune response and is important for further tumor growth
      and stroma formation. We investigated two lymphoma cell lines of the same origin,
      differing in immunogenicity: non-immunogenic parental strain P388 and its highly
      immunogenic subline P388/adria. Early systemic inflammatory response resulted in
      the enhancement of nitric oxide (NO) and superoxide production by peritoneal
      macrophages which was at a maximum on the first day after s.c. tumor inoculation
      and was observed in mice bearing either of these tumors independently of
      immunogenicity. It was followed by a transient elevation of the serum levels of
      pro-inflammatory cytokines: TNF-alpha IL-6. In order to evaluate the role of
      inflammatory response, vaccinations with lethally irradiated lymphoma cells were
      performed. After two weekly injections, the mice were challenged s.c. with live
      tumor cells of the same subline. Effective vaccination with P388/adria lymphoma
      cells induced retardation of tumor growth in parallel with down-regulation of
      peritoneal macrophage activity and abrogation of serum cytokine release. Non
      effective immunization with P388 cells influenced neither tumor growth nor
      macrophage functions and cytokine level. Thus, a positive correlation was found
      between down-regulation of the inflammatory response and inhibition of tumor
      growth. We suppose that, in efficiently immunized mice, special mechanisms exist
      which are responsible for down-regulation of the inflammatory reaction.
      Macrophage products may facilitate tumor cell survival by preventing apoptosis or
      participate in the activation of tumor neoangiogenesis. Suppression of these
      activities may serve as an important tool for the inhibition of tumor growth at
      the early stages of malignant transformation.

PMID- 11848514
TI  - Cytotoxic compounds from Annonaceus species as DNA topoisomerase I poisons.
AB  - BACKGROUND: In the search for cytotoxic natural products as DNA topoisomerase
      poisons, we have assessed six annonaceus compounds (the acetogenins annonacin and
      rolliniastatin-1, the styryl-lactones etharversin and altholactone and the
      alkaloids thaligrisine and cepharanone-B) for cytotoxic activity against three
      human cancer cell lines and then we evaluated these compounds as DNA
      topoisomerase poisons. MATERIALS AND METHODS: The cytotoxicity parameters were
      determined following protocols established by the National Cancer Institute (NCI)
      using the SRB assay. In the topoisomerase assay, the supercoiled DNA produces
      open circle forms that are stabilised in the presence of DNA topoisomerase
      poisons and can be detected after a denaturation step by proteinase K-SDS.
      RESULTS: The six compounds showed cytotoxic activity, with cepharanone B being
      the most cytotoxic one, even more than the antineoplastic agent etoposide on two
      cancer cell lines, although it is the only one that does not act as a DNA
      topoisomerase poison. CONCLUSION: These results could justify the traditional use
      of the studied annonaceus species and topoisomerase-mediated DNA damage might be
      a possible mechanism by which five of these compounds exert their cytotoxicity.

PMID- 11848513
TI  - Activation of caspase-3 protease during the process of ursolic acid and its
      derivative-induced apoptosis.
AB  - The apoptosis-inducing effect of the triterpene saponins, namely, ursolic acid
      and its natural derivative, methyl-ursolate beta-D-glucoside on A431 human
      epidermoid carcinoma cells was studied. The cells treated with 5-50 microg/ml of
      ursolic acid resulted in a dose- and time-dependent decrease in cell number, due
      to an increase of apoptotic cells as evidenced by MTT assay together with
      morphological changes. The highest dose (50 microg/ml) of ursolic acid resulted
      in approximately 90% inhibition in tumor cell growth after 96 hours of treatment
      and 60% of apoptosis after 48 hours. To the contrary, when the same treatment was
      carried out with methyl-ursolate beta-D-glucoside, after 96 hours of treatment
      the percentage of cell growth inhibition was found to be only 30% at the dose of
      50 microg/ml and the value of apoptosis did not exceed 10%. Similarly to these
      results, ursolic acid effectively induced proteolytic activation of caspase-3
      protease in a dose-dependent manner while its derivative showed only weak
      activity in this enzyme assay. The addition of DEVD-CHO prior to ursolic acid and
      methyl-ursolate beta-D-glucoside treatment effectively prevented the loss of
      triterpenes-induced viability. In summary, the triterpene saponins investigated
      contain an apoptotic-inducing activity in A431 cells and in the case of ursolic
      acid it is associated with proteolytic activation of caspase-3 and/or other
      similar caspases. Our results also indicated that methylation of COOH-28 together
      with the glycosylation of C3 of ursolic acid have a strong impact on its
      antitumor activity.

PMID- 11848515
TI  - TNFalpha contributes to the antitumor activity of a bispecific, trifunctional
      antibody.
AB  - Immunological cancer therapies focus on the activation of immune effector cells
      yielding a specific antitumor activity. Disseminated tumor cells are regarded as
      the origin of metastases and consequently their elimination is the central
      objective of adjuvant immune therapies. The use of bispecific antibodies is an
      approach that is regarded as promising in order to fight those disseminated tumor
      cells. Unfortunately, the efficiency of these antibodies is limited by the fact
      that they usually activate a single class of effector cell, thus not yielding
      optimal immune response. In addition, tumor cells may down-regulate the
      antibody's target molecule and escape recognition. We have recently described
      results with an intact bispecific molecule, BiUII, that represents a new class of
      intact antibodies. These antibodies, termed "triomab", provide an excellent
      antitumor activity in vitro, a fact that most probably is attributable to the
      simultaneous activation of different classes of immune effector cells. We have
      now investigated this antitumor activity in more detail and demonstrate here that
      at least a dual mechanism accounts for triomab-mediated killing of tumor cells:
      besides direct cell-mediated killing, triomab induces the production of TNFalpha
      in PBMCs at concentrations that induce apoptosis in target cells. This bystander
      effect may be of special interest for the clinical application of triomab in
      terms of killing of target antigen-negative tumor cells.

PMID- 11848516
TI  - Identification by suppression subtractive hybridization of p21 as a radio
      inducible gene in human glioma cells.
AB  - BACKGROUND: Radio-gene therapy involves the delivery, to tumor cells, of a
      therapeutic transgene whose expression is controlled by irradiation. MATERIALS
      AND METHODS: Here, we sought to identify novel radio-inducible transcripts in
      U87MG human malignant glioma cells using suppression subtractive hybridization
      (SSH). RESULTS: Of 998 clones from a subtracted library of irradiated U87MG
      cells, 24 candidate clones were identified by dot blot and 3 clones were
      confirmed as having been induced by irradiation by Northern blot analysis. All
      three clones showed 99-100% homology to the cyclin-dependent kinase (cdk)
      inhibitor, p21(Waf/Cip1). A screening of 12 human malignant glioma cell lines
      revealed that irradiation increased p21 mRNA expression and p21 protein levels
      levels in all of the five cell lines retaining p53 wild-type activity in a p53
      reporter assay, but in none of seven p53 reporter-negative cell lines.
      CONCLUSION: Irradiation induces p21 mRNA expression in a strictly p53-dependent
      manner and may only enhance the expression of a limited number of genes in glioma
      cells. We conclude that the identification of radio-inducible genomic sequences
      suitable for radio-gene therapy may turn out to be difficult.

PMID- 11848517
TI  - Topotecan (Hycamtin) responsiveness in human renal carcinoma cell lines of the
      clear cell and papillary types.
AB  - BACKGROUND: Since no effective therapeutic approach is yet known for metastatic
      renal cell carcinoma (RCC), we analyzed the effects of topotecan (Hycamtin), a
      novel topoisomerase I-inhibitor, in RCC cell lines of the clear cell and
      papillary/chromophilic types. MATERIALS AND METHODS: The anti-proliferative and
      apoptosis-inducing effects of topotecan were analyzed in 20 RCC cell lines by MTT
      assay and light microscopic apoptosis counting. Moreover, Bcl-2 and Bax
      expression was investigated by Northern blot and immunocytochemistry while the
      p53 mutation status was analyzed by DNA sequencing. RESULTS: Exposure to
      clinically relevant concentrations of topotecan (i.e. < or = 1 microg/ml)
      resulted in a significant (p<0.05) dose-dependent reduction of cell number in 17
      out of 20 RCC cell lines. The reduction of cell number was paralleled by an
      increase in apoptotic cell death. Papillary/chromophilic RCCs exhibited a
      significantly (p<0.05) more pronounced responsiveness to topotecan than clear
      cell RCCs. Moreover, the effects of topotecan proved to be superior to those of 5
      fluorouracil (5-FU), an anticancer drug currently used in the therapy of RCCs. No
      correlation became evident between responsiveness to topotecan and the expression
      levels of Bcl-2 and Bax. Moreover, the response to topotecan could not be
      correlated with the p53 mutation status of our RCC cell lines. CONCLUSION:
      Clinically relevant concentrations of topotecan induced apoptosis in RCC cell
      lines more effectively than 5-FU. Further testing will show whether topotecan
      induced apoptosis can be exploited for the treatment of RCCs in vivo as well.

PMID- 11848518
TI  - Ajoene, a garlic-derived natural compound, enhances chemotherapy-induced
      apoptosis in human myeloid leukaemia CD34-positive resistant cells.
AB  - The reputation of garlic as an effective remedy for tumours extends back to the
      Egyptian Codex Ebers of 1550 BC. Several garlic compounds, including allicin and
      its corresponding sulfide, inhibit the proliferation of several human malignant
      cells. Ajoene is a garlic-derived compound produced most efficiently from pure
      allicin and has the advantage of a greater chemical stability than allicin.
      Recently, ajoene was shown to inhibit proliferation and induce apoptosis of human
      leukaemia CD34-negative cells including HL-60, U937, HEL and OCIM-I. More
      significantly, ajoene was shown to induce 30% apoptosis in myeloblasts from a
      chronic myeloid leukaemia patient in blastic crisis. Acute myeloid leukaemia
      (AML) is a heterogeneous malignant disease in which disease progression at the
      level of CD34-positive cells has a major impact on resistance to chemotherapy and
      relapse. MATERIALS AND METHODS: The aim of the present study was to investigate
      the effect of ajoene on changes in the expression of apoptosis-related proteins:
      bcl-2 and caspase-3, induced by two principal drugs used in treatment of AML,
      cytarabine and fludarabine, in KGI human myeloid leukaemia CD34-positive
      resistant cells. Both quantitative ELISA measurement of bcl-2 and colourimetric
      measurement of active caspase-3 were used. RESULTS: Quantitative ELISA
      measurement of bcl-2 (units per million cells) showed treatment of KG1-resistant
      leukaemia cells with 40 microM ajoene alone to significantly reduce the bcl-2
      expression from 239.5 +/- 1.5 in control cultures to only 22.0 +/- 4.0 in ajoene
      treated cultures. Fludarabine had significantly more inhibitory effect on bcl-2
      expression than cytarabine in KGI-resistant myeloid leukaemia cells. Ajoene
      significantly enhanced the inhibitory effect of the two chemotherapeutic drugs,
      cytarabine and fludarabine, on bcl-2-expression in KGI cells. Bcl-2-expression
      could not be detected in fludarabine + ajoene-treated cultures. The Western blot
      of bcl-2-expression in KGI control and treated cells confirmed the quantitative
      ELISA measurements. Quantitative measurement of activated caspase-3 (pg per
      million cells) showed the two drugs, cytarabine and fludarabine, significantly
      increased the activated caspase-3 level in KGI myeloid leukaemia cells.
      CONCLUSION: The addition of ajoene enhanced the activation of caspase-3 in both
      cytarabine- and fludarabine-treated KGI cells. In conclusion, the present results
      suggest a potential role for the combination of ajoene with fludarabine-based
      chemotherapy in the treatment of refractory and/or relapsed AML patients. Further
      studies are warranted to evaluate a similar enhancing effect for ajoene in blast
      cells from AML patients in primary cultures.

PMID- 11848519
TI  - Neoadjuvant chemotherapy and concurrent chemoradiation in the treatment of
      advanced cervical cancer.
AB  - The role of chemotherapy in the management of advanced cervical cancer has been
      long debated. Whereas some phase II trials have shown promising results with
      neoadjuvant chemotherapy followed by irradiation, most phase III trials failed to
      demonstrate any benefit with this sequential treatment in terms of loco-regional
      control and survival, mainly because chemotherapy could cause accelerated tumor
      clonogen resistant cell repopulation The data on cisplatin-based neoadjuvant
      chemotherapy before surgery appear to be more promising. This treatment modality
      can increase the operability rate and reduce the incidence of positive nodes and
      other pathological risk factors. However, very few randomized trials comparing
      cisplatin-based neoadjuvant chemotherapy followed by radical hysterectomy versus
      conventional irradiation treatment are currently available, whilst data about
      long-term survival of chemo-surgical-treated patients are scanty. Recently five
      prospective randomized trials compared concurrent cisplatin-based chemotherapy
      and irradiation versus hydroxyurea plus irradiation or irradiation alone. All
      showed a significant improvement in the outcome of patients treated with
      concurrent cisplatin-based chemoradiation. Based on these data, the National
      Cancer Institute released a Clinical Announcement stating that concurrent
      cisplatin-based chemoradiation should be the new standard of therapy for high
      risk early stage and locally advanced cervical cancer. The introduction of
      taxanes in both neoadjuvant chemotherapy followed by radical hysterectomy and
      concurrent chemoradiation could further improve the results of these two
      treatment modalities. A multicenter randomized trial comparing chemo-surgical
      treatment with concurrent chemoradiation is warranted to better define the
      optimum therapeutic strategy for patients with advanced cervical cancer.

PMID- 11848521
TI  - Perspectives in the treatment of malignant gliomas in adults.
AB  - Over the last two decades, after establishing the role of postoperative
      radiotherapy for malignant gliomas, no definitive improvement in survival rate
      could be observed, despite advances in established treatment modalities such as
      radiotherapy and chemotherapy. Progress in exploration of the biology of these
      tumours allowed for translational research projects and the development of
      rational new approaches, such as gene therapy and immunotherapy, that could
      interfere with established treatment regimens or be used independently. Possible
      strategies include the restoration of defective cancer-inhibitory genes, cell
      transduction or transfection with antisense DNA corresponding to genes coding for
      growth factors and their receptors, or with the so-called 'suicide genes'.
      Several antiangiogenic approaches such as administration of thalidomide,
      protamine, or monoclonal antibodies against vascular endothelial growth factor
      have been developed, too. Further treatment possibilities include modulation of
      drug resistance, e.g. by P-glycoprotein antagonists or 06-alkyl-guanine-DNA
      transferase inhibitors, inhibition of matrix metalloproteinases, inhibition of
      protein kinase C and administration of agents such as phenylbutyrate or valproic
      acid that showed promising antiproliferative effects in vitro. This review
      discusses the available laboratory and clinical data as well as recent advances
      in our knowledge about prognostic and predictive factors and their implications
      for the design of future clinical trials.

PMID- 11848522
TI  - Long time therapy with topotecan in patients with recurrence of ovarian
      carcinoma.
AB  - BACKGROUND: In several phase II and III topotecan studies the large number of
      patients with stable disease is striking. Since no severe organ toxicity has been
      described for topotecan, long-term therapy with topotecan seems to be reasonable.
      In this summary we present evidence, that long-term topotecan therapy can be
      managed without cumulative hematological and non-hematological toxicity. PATIENTS
      AND METHODS: Thirty-three patients with recurrent ovarian cancer, who were
      treated with at least 7 courses of topotecan, were evaluated in this
      retrospective study (patient database from SmithKline Beecham, Germany). Most of
      the patients had more than 2 previous courses of chemotherapy. The starting dose
      was between 1.0 and 1.5 mg/m2 topotecan administered for 5 days every 3 weeks as
      an i.v. infusion. All patients were evaluated for toxicity, 32 patients for
      response. RESULTS: The 33 patients received 343 courses of topotecan, an average
      of more than 10 courses per patient. The highest number of courses given to a
      single patient was 33. The hematotoxicity was in the expected range, but toxicity
      was not cumulative. The number of interventions for growth factors and blood cell
      transfusions were constant over the whole therapy. Dose reductions were conducted
      in more than 75% of the patients as early as in course two. There was no grade 3
      or 4 non-hematological toxicity. Alopecia was the only toxicity to be cumulative.
      Remissions were observed in 12 out of 32 eligible patients. The remissions were
      achieved after an average of 4.3 courses (range 2-7). The median time to
      progression was 33 weeks. CONCLUSION: Long-term therapy with topotecan is
      reasonable and can be conducted without cumulative hematological toxicity.

PMID- 11848520
TI  - Cyclin D1 overexpression is more prevalent in non-Caucasian breast cancer.
AB  - African-American women with breast cancer consistently show a shortened survival
      when compared with Caucasians with breast cancer, however it is not clear whether
      this is due to socioeconomic factors or to racial differences in tumor biology.
      Cyclin D1 overexpression has been demonstrated in 60-80% of female breast
      cancers, however these studies have not included race or ethnicity data. We
      examined the level of cyclin D1 protein expression in 139 cases of female breast
      cancer obtained from different ethnic populations. Using an immunoperoxidase
      based technique and a polyclonal anti-cyclin D1 antibody, the rate of
      overexpression was 68%. Cyclin D1 overexpression tended to be more frequent in
      cases from non-Caucasian patients when compared with those from Caucasian
      patients (77% vs. 59%, p=0.051). Our findings suggest that non-Caucasian
      ethnicity may be important in predicting cyclin D1 overexpression. Cyclin D1
      could therefore serve as a possible target in managing breast cancer in the
      African-American population.

PMID- 11848523
TI  - Treatment options in patients with recurrent ovarian cancer.
AB  - The majority of patients with advanced ovarian cancer need a second-line
      treatment for recurrent disease after surgical cytoreduction and first-line
      chemotherapy. In these patients, treatment planning is mainly dependent on the
      platinum-free-interval. The patients may be distinguished as platinum-refractory
      (progression under platinum-based therapy), platinum-resistant (relapse within 6
      months), or platinum-sensitive (relapse after 6 months). Patients with platinum
      refractory or -resistant disease should be encouraged to enter clinical trials.
      Alternatively, these patients could receive tamoxifen or a non-platinum single
      agent therapy. Since response rate and duration to different single-agents are
      similar, patient convenience, toxicities from prior treatment, side-effects and
      costs play a role in the drug selection for salvage chemotherapy. Patients with
      platinum-sensitive disease should receive carboplatin based or carboplatin-plus
      paclitaxel-based regimens. Secondary surgical cytoreduction may have a role in
      highly selected patients with good performance status, with long disease-free
      interval and without extra-abdominal or liver metastases.

PMID- 11848524
TI  - Conversion of nested reverse-transcriptase polymerase chain reaction from
      positive to negative status at peripheral blood during androgen ablation therapy
      is associated with long progression-free survival in stage D2 prostate cancer
      patients.
AB  - BACKGROUND: Nested reverse-transcriptase polymerase chain reaction (nested rt
      PCR) for the detection of mRNA of prostate specific antigen (PSA) and prostate
      specific membrane antigen (PSMA) in peripheral blood samples (PB) and bone marrow
      biopsies (BM) can assess the extraprostatic growth of prostate cells. MATERIALS
      AND METHODS: Nested rt-PCR for PSA and PSMA at PB and BM was performed (a) at
      diagnosis, (b) after 6 months from the initiation of combined androgen blockade
      [(CAB); triptorelin 3.75 mg, i.m., q28 days plus flutamide 250 mg, per os, tid]
      and, (c) at progression to androgen refractory stage in 28 patients with newly
      diagnosed stage D2 prostate cancer. RESULTS: At diagnosis, all patients were
      found to be rt-PCR positive for PSA and PSMA at BM while 7 (25%) were rt-PCR
      negative for PSA and PSMA at PB. Nine out of 21 patients with rt-PCR-positive
      status have converted to rt-PCR-negative status at PB during CAB while they
      remained rt-PCR-positive at BM. The rt-PCR-negative status at PB during CAB was
      associated with progression-free survival >12 months (p=0.029). At progression to
      androgen refractory stage all but 2 patients were rt-PCR-positive at PB for PSA
      and PSMA, among them 3 who were rt-PCR-negative at diagnosis. CONCLUSION: Our
      data suggest that conversion to rt-PCR-negative status at PB for PSA and PSMA
      during objective clinical response to CAB is associated with long progression
      free survival in stage D2 disease.

PMID- 11848525
TI  - Immunoscintigraphy with a technetium-99m labelled anti-epithelial growth factor
      receptor antibody in patients with non-small cell lung cancer.
AB  - BACKGROUND: A variety of human tumours, including non-small cell lung cancer,
      overexpress epithelial growth factor (EGF) receptors. In this study we evaluated
      the feasibility of immunoscintigraphy with a technetium-99m-labelled monoclonal
      antibody directed towards the EGF receptor (MINT5). MATERIALS AND METHODS: The
      labelling with technetium-99m was performed using the glucoheptonate
      iminothiolane method. Eight patients with non-small cell lung cancer were i.v.
      injected 740 MBq of MINT5. Neither side-effects, nor toxicity, nor HAMA response
      were observed. Each patient was submitted to total body planar images in anterior
      and posterior projections at 1-2 hours and at 4-6 hours after the injection.
      RESULTS: Uptake of MINT5 was mainly visible in liver, spleen and bone marrow; it
      proved stable in vivo. The primary lung cancer was imaged in 7 out of 8 patients
      and metastases were detected in 3 out of 3 cases. CONCLUSION: MINT5 is a safe and
      promising radiopharmaceutical for in vivo localization and biological
      characterization of non-small cell lung cancer.

PMID- 11848526
TI  - First line combination chemotherapy with docetaxel and vinorelbine in advanced
      breast cancer. A phase II study.
AB  - We evaluated the efficacy and tolerance of the combination of docetaxel and
      vinorelbine as first line treatment in metastatic breast cancer (MBC). These
      agents have different mechanisms of action and both are active in advanced breast
      cancer. Thirty-nine chemotherapy-naive for metastatic disease patients were
      treated on an out-patient basis with vinorelbine 20 mg/m2 i.v. on days 1 and 8
      and docetaxel 85 mg/m2 i.v. on day 8, every 3 weeks. Twenty-one (53.8%) patients
      had locoregional disease, 30 (76.9%) had distant metastases and 20 (51.3%) had
      visceral metastases. The intent-to-treat objective response rate (RR) was 48.75%
      (19 out of 39 patients; 95% confidence interval (CI), 32.4% to 65.2%). Four
      patients (10.25%) achieved a complete response (CR) (95% CI, 2.9% to 24.2%) and
      15 (38.5%) a partial response (PR) (95% CI, 23.4% to 55.4%). The median duration
      of response was 4 months, the median time to progression (TTP) was 6 months and
      the median survival-time was 11.3 months. Grade 3 and/or 4 (3/4) anemia and
      thrombocytopenia occurred in 7.7% and 5.1% of patients, respectively. Twelve
      (30.7%) patients developed grade 3/4 neutropenia and 7 (17.9 %) were complicated
      with fever. Grade 3/4 diarrhea, nausea-vomiting, fatigue and constipation were
      not a problem. Alopecia was universal. Grade 3/4 neurotoxicity was evident in
      2.6% of patients. None of the patients developed allergic reaction or fluid
      retention. There was one treatment-related death due to grade 4 neutropenia and
      sepsis. CONCLUSION: This combination of docetaxel and vinorelbine, a non
      anthracycline-containing regimen, is a moderately effective regimen for the
      treatment of chemotherapy-naive breast cancer patients with metastases, causing
      only mild to moderate toxicity.

PMID- 11848527
TI  - KAI1/CD82 expression as a prognosic factor in sporadic colorectal cancer.
AB  - BACKGROUND: Since its identification as a suppressor gene for prostate cancer
      metastasis, down-regulation of KAI1/CD82 in a variety of malignancies has been
      reported. MATERIALS AND METHODS: Using immunohistochemistry, we examined
      KAI1/CD82 expression in surgical specimens obtained from 70 patients with
      advanced colorectal cancer and its correlation with clinicopathological factors,
      to clarify their prognostic significance. RESULTS: KAI1/CD82 expression was
      positive in 55% of the 70 colorectal cancers. There were statistically
      significant correlations between KAI1/CD82 expression and Dukes' stage, venous
      invasion, lymph node metastasis, tumor differentiation and liver metastasis. The
      significant correlation between KAI1/CD82 expression and outcome among patients
      with Dukes' C cancer (p=0.024) is particularly noteworthy. On multivariate
      analysis, KAI1/CD82 expression and Dukes' stage were identified as significant
      and independent prognostic factors (p=0.006 and 0.045, respectively). CONCLUSION:
      KAI1/CD82 expression closely correlates with clinicopathological factors for
      colorectal cancers. KAI1/CD82 expression appears to be a useful prognostic
      marker.

PMID- 11848528
TI  - Recent results in the surgical treatment of gastric cancer according to the
      Japanese and TNM classification.
AB  - BACKGROUND: Recent outcomes based on surgical long-term follow-up of patients
      with gastric cancer using current staging systems have not been fully evaluated.
      MATERIALS AND METHODS: A total of 1357 patients with primary gastric carcinoma
      (911 males and 446 females, ranging in age from 20 to 87 years; average 59.1
      years) who had undergone gastric resection between 1986 and 1996 were examined
      with respect to their clinicopathological features, surgical procedures and
      patient survival according to Japanese and UICC-TNM classifications. RESULTS: The
      5-year survival rate was 95.3% for stage Ia, 85.5% for stage Ib, 73.8% for stage
      II, 45.7% for stage IIIa, 20.9% for stage IIIb, 17.3% for stage IVa and 5.8% for
      stage IVb (8.8% for IVa and IVb) on the Japanese classification. By way of
      contrast, the 5-year survival rate was 95.6% for stage Ia, 85.0% for stage Ib,
      72.1% for stage II, 49.3% for stage IIIa, 30.2% for stage IIIb and 12.0% for
      stage IV on the TNM classification. CONCLUSION: Although minor problems are
      associated with both the Japanese and TNM classification systems, both appear to
      be clinically significant and appropriate independent predictors of prognosis.
      The findings of the present study provide important information for comparing
      results among different institutes and for introducing new clinical trials for
      gastric cancer at the beginning of the new century.

PMID- 11848529
TI  - Serum soluble Fas level for detection and staging of prostate cancer.
AB  - To evaluate the clinical usefulness of measuring serum soluble Fas (sFas) for
      differentiation between prostate cancer and benign prostate hyperplasia (BPH) and
      for staging of prostate cancer, serum sFas and PSA were determined in 38 and 20
      men with prostate cancer and BPH, respectively, before treatment. In 17 patients,
      sFas and PSA were measured one hour after transrectal ultrasound-guided sextant
      biopsy in order to examine the leakage of sFas into the circulation after
      prostatic injury. Patients with prostate cancer had a significantly higher level
      of sFas than those with BPH. The serum sFas level was statistically elevated in
      patients with metastatic prostate cancer. There was a statistically significant
      correlation between sFas and PSA in patients with prostate cancer but not in
      those without cancer. The serum sFas did not change one hour after systematic
      prostatic biopsy although PSA levels were markedly elevated. sFas levels might be
      useful as a discriminator between prostate cancer and BPH while sFas might
      indicate the tumor burden in patients with prostate cancer.

PMID- 11848530
TI  - Surgical pathology examination of radical prostatectomy specimens. Updated
      protocol based on the Italian TAP study.
AB  - Between January 1996 and June 2000, 192 men with prostate cancer underwent
      radical retropubic prostatectomy (RP) and bilateral pelvic node dissection in 26
      centers participating in the Italian randomized prospective TAP study. The
      reviewing pathologist evaluated 145 RP specimens. Seventy-five cases had not been
      treated with total androgen ablation before RP was performed, whereas 70 had been
      treated for three months. Whole-mount sectioning of the complete radical
      prostatectomy specimens was adopted in each center for accurately evaluating the
      pathological stage of prostate cancer and resection limit status. The results of
      this study suggest that total androgen ablation before RP is beneficial in men
      with clinical stage T2 because of the significant pathological down-staging and
      decrease in the number of positive margins in the RP specimens. On the basis of
      the experience acquired through the Italian TAP study and recent publications on
      prognostic factors in prostate cancer, the original practice protocol for
      examination of RP specimens removed from patients with carcinoma of the prostate
      glands was updated.

PMID- 11848531
TI  - Assessment of soft tissue lesions suspicious for liposarcoma by F18-deoxyglucose
      (FDG) positron emission tomography (PET).
AB  - BACKGROUND: F18-deoxyglucose (FDG) positron emission tomography (PET) is a
      promising imaging technique. The aim of this study was to investigate the use of
      FDG PET in patients with suspected liposarcomas (LS). PATIENTS AND METHODS: Forty
      two masses were studied. The FDG uptake was estimated in tumor (T) and normal
      tissue (NT). The data were analyzed with respect to pathological findings.
      RESULTS: Pathology revealed 11 primary LS, 14 locally recurrent LS, 5 other
      sarcomas, 1 inflammation, 1 lymphoma and 10 benign lesions. FDG uptake (T-to-NT
      ratio) in 25 LS corresponded with the histological subtype. Pleomorphic, mixed
      and myxoid LS showed an increased T-to-NT ratio and were thus visualized. Four
      out of six well-differentiated LS presented a low FDG uptake. Like subtype, the
      tumor grade also corresponded to FDG uptake. The T-to-NT ratio of higher grade
      LS, contrary to low grade LS, was uniformly increased. Primary LS were
      distinguishable from benign tumors, while other sarcomas, inflammation and
      lymphoma were not. Recurrence was detected with a sensitivity of 86% and a
      specificity of 100%. False-negative diagnoses occurred only in well
      differentiated recurrences. CONCLUSION: FDG uptake in LS correlates with the
      histological subtype and tumor grade. The diagnostic value of FDG PET in LS,
      therefore, is influenced by histomorphological parameters. Our data suggest that
      pleomorphic, mixed and higher-grade LS recurrences are preferentially amenable to
      FDG PET imaging.

PMID- 11848532
TI  - Ki-67 expression and residual tumour (R) classification are associated with
      disease-free survival in desmoid tumour patients.
AB  - BACKGROUND: In order to evaluate prognostic factors in the long-term survival of
      desmoid tumour patients, analysis of clinicopathological, immunohistochemical and
      follow-up data was performed. PATIENTS AND METHODS: Between 1969 and 1998, 54
      patients underwent resection of aggressive fibromatosis (desmoid) and 33 of them
      (10 patients with FAP and 23 sporadic) were followed-up with a median time of 130
      months (range 10-355 months). Additionally, immunohistochemical analysis of the
      desmoid tumours using Ki-67 was performed. RESULTS: In univariate analysis,
      curative resection (R0) (p<0.001) and low proliferation of Ki-67 (p=0.002) were
      of significant positive prognostic value concerning disease-free survivaL R0 and
      absence of Ki-67 staining were significantly associated with each other
      (p=0.004). CONCLUSION: Ki-67 seems to serve as a predictive marker concerning
      disease-free survival of desmoid tumour patients. In patients presenting with Ki
      67 positive desmoids, which are unlikely to be resected in a curative manner,
      alternative treatment (e.g. sulindac) may be preferable.

PMID- 11848533
TI  - Plasmatic cytokine network in patients with laryngeal carcinoma after surgical
      treatment.
AB  - Alterations in host immunity, inflammation, angiogenesis and metabolism are all
      prominent clinical features in patients with laryngeal squamous cell carcinoma
      (LSCC). Although the origin of the signals and mechanisms underlying these
      responses are not well understood, their local and systematic nature suggest that
      squamous cell carcinoma-produced cytokines with proinflammatory and
      immunoregulatory activity may contribute to the pathogenesis of LSCC. In order to
      gain a better insight into the roles and relationships of the cytokines, we
      investigated serum IL-6, IL-10 and IL-12 concentrations in LSCC patients under
      baseline conditions and after surgery. In comparison with controls, all the
      patients had higher plasma IL-10 concentrations before surgical treatment (T0),
      while plasma IL-6 and IL-12 concentrations were higher in 22 (84.6%) and 24
      patients (92.3%). The differences in plasma IL-6, IL-10 and IL-12 concentrations
      at T0 and T1 were statistically significant (p<0.001, p<0.0046 and p<0.011). Our
      finding suggest that plasma cytokines are overexpressed in LSCC patients. There
      was an independent increase in plasma IL-6 levels before and after surgical
      treatment. Furthermore, the up- and down-regulation of plasma IL-10 and IL-12
      suggest a regulatory relationship between them.

PMID- 11848534
TI  - A model of BAX gene delivery to human lung cancer.
AB  - In this report we have investigated the effects of BAX in enhancing apoptosis in
      two primary non-small cell lung cancer cell lines. A count of the apoptotic cells
      by TUNEL staining revealed that almost 70% of BAX over-expressing cells died,
      while very few apoptotic cells were detectable in the wildtype cells or in the
      cells transfected with an empty vector. These findings suggest that de-regulated
      expression of BAX may provide a novel mechanism for initiating cell death in non
      small cell lung cancer cells. Further studies are needed to better define the
      involvement of this protein in the complex mechanism of lung carcinogenesis and
      to definitely demonstrate the therapeutic utility of targeting this pathway.

PMID- 11848535
TI  - Familial cancer diagnosis.
AB  - Familial clustering of cancer is well known from epidemiologic studies. This can
      be due to chance, shared environmental influences, shared genes and chance
      environmental-genetic interactions. Family studies are a key to the understanding
      of the environmental and genetic etiology of chronic disease. Cancer families are
      human models of susceptibility to neoplasia. More and more people are aware of,
      and anxious about, their cancer risk. High-risk individuals can benefit from
      prevention and early detection programs. In medical practice the patient workup
      should include a carefully obtained family history. This low technology method
      has the potential for reduction of cancer morbidity and mortality. Every person
      should create his/her own family tree and discuss it with his/her doctor. This is
      a step each individual can take for his/her health.

PMID- 11848536
TI  - The prognostic significance of proliferative activity, apoptosis and expression
      of DNA topoisomerase II alpha in multimodally-treated oesophageal squamous cell
      carcinoma.
AB  - The present study retrospectively examined the correlation between the outcome of
      patients with locally advanced oesophageal squamous cell carcinoma (cT3-4 cN0-1
      cM0) after multimodal treatment (radiochemotherapy +/- surgical resection) and
      the parameters proliferative activity, apoptotic index and expression of the
      nuclear enzyme topoisomerase II alpha (topo II alpha) in pre-therapeutic tumour
      biopsies. Fifty-eight patients who took part in a prospective multicentred trial
      received radiochemotherapy, optionally followed by surgery. Pre-therapeutic
      biopsies were immunohistochemically investigated for the extent of proliferation
      (MIB-I index) and expression of the topo II alpha-enzyme. The apoptotic index was
      determined by the TUNEL-assay. The three parameters were correlated with tumour
      response to polychemotherapy and with overall survival. Topo II alpha expression
      was found in all samples with different percentages of positive cells. The
      proliferation indices ranged between 9% and 97% (median: 43%) while the apoptotic
      indices ranged between 0.2% and 2.8% (median: 0.5%). Strong expression of topo II
      alpha (>50% positive tumour cells) was positively-correlated with response to
      polychemotherapy (p=0.016) whereas proliferative activity or apoptotic index
      showed no impact. None of the three parameters under investigation was predictive
      of overall survival. Pre-therapeutic determination of topo II alpha expression
      may predict chemosensitivity of oesophageal squamous cell carcinomas. However,
      determination of proliferative activity and apoptotic index has no predictive
      value.

PMID- 11848537
TI  - Expression of nm23 gene in gastric cancer is associated with a poor 5-year
      survival.
AB  - The nm23 gene is thought to play a role as an inhibitor of metastatic progression
      in several human cancers and its down-regulation has been associated with
      increased metastasis and reduced survival in some studies, though not in others.
      To better investigate the role of nm23 in gastric cancer (GC), the expression and
      prognostic impact of this gene was examined in 107 radically operated GC patients
      in a high risk area. The expression of nm23 was determined immunohistochemically
      by using the rabbit antibody anti-human nm23 protein. The expression of nm23 was
      detected in 40.2% (n = 43) of 107 gastric tumours and correlated with a poorer
      clinical outcome. In a survival analysis at 5 years, patients with nm23-positive
      tumours had significantly worse prognosis than patients (n = 64) with nm23
      negative tumours (p < 0.05). The prognostic significance of nm23 expression was
      confirmed by multivariate analysis including terms for tumour stage and lymph
      node involvement. Our results suggest that the expression of the nm23 gene in
      gastric carcinoma is significantly related to tumour progression and poor
      prognosis at 5 years.

PMID- 11848538
TI  - Fibrosarcoma of the uterus: a case report.
AB  - BACKGROUND: This case report presents the management of a patient with
      fibrosarcoma of the uterus. Until recently, no cases of fibrosarcomas of the
      uterus have been reported in the literature. CASE REPORT: A 40-year-old woman
      presented with complaints of slight vaginal bleeding, watery, white discharge and
      abdominal pain of 3 weeks' duration. The patient underwent total abdominal
      hysterectomy. Intraoperative findings included an enlarged irregular-shaped
      uterus with lots of leiomyoma nodules. The largest leiomyoma nodule was about 8
      cm in size and contained an area classified as a fibrosarcoma, presenting
      cellular immature-appearing fibroblasts growing in a fascicular arrangement.
      Because of the limited extension of the fibrosarcoma, no adjuvant therapy was
      performed. After surgical therapy the patient was followed without any evidence
      of disease for five years. CONCLUSION: Fibrosarcoma is a poorly-circumscribed
      infiltrative spindle soft tissue sarcoma, which is characterized by local growth
      and has a propensity for local recurrence. Metastases can occur, mostly to lung
      and bone. The treatment of choice is wide surgical excision usually followed by
      radiation therapy due to the high local recurrence rate.

PMID- 11848539
TI  - Dysregulative lymphoma theory revisited; what can we learn from cytokines, CD
      classes and genes?
AB  - Based largely on animal experiments, a dysregulative lymphoma theory was designed
      some 15 years ago as a basis for computer simulation studies. The basic concept
      of this theory was that lymphomas arise when persistent immunostimulation
      coincides with some kind of immune deficiency. The present article reviews
      exemplary data from human lymphoma cases in an attempt to further support or to
      reject the hypothesis. T- and B-cell lymphomas according to the REAL
      classification were reviewed with regard to the functional effects of their CD
      markers and their ligands, interleukin activities and cytogenetic changes. The
      results are summarized and further discussed. Essentially in all cases, a
      combination of enhanced stimulation of lymphoid cells and functional deficiency
      is identified, thus supporting the general pathogenetic hypothesis of malignant
      lymphomas. Despite using the most modem lymphoma classification, however,
      lymphoma entities and theirfunctional changes are so heterogeneous that cases
      need to be studied individually when it comes to pathogenetic considerations.

PMID- 11848540
TI  - Safety and advantage of perioperative autologous blood transfusion in hepatic
      resection for hepatocellular carcinoma.
AB  - BACKGROUND: The safety and advantages of perioperative autologous blood
      transfusion (ABT) were evaluated on hepatectomy for hepatocellular carcinoma
      (HCC). MATERIALS AND METHODS: Blood samples were obtained and stored from 30
      patients with HCC. HCC cells were investigated by the presence of AFPmRNA using
      RT-PCR after storage. We also reviewed postoperative liver function and the long
      term outcomes of 138 patients who underwent hepatectomy receiving ABT compared
      with patients receiving homologous blood transfusion (HBT) and patients without
      blood transfusion. RESULTS: AFPmRNA was not detected in all samples stored for
      more than 14 days. Postoperative ALT, AST and total bilirubin in the HBT group
      were significantly higher than those of other groups. Patients in the HBT group
      had significantly lower survival rates than patients in the ABT group.
      CONCLUSION: ABT was safe after storage and it had advantages compared with HBT
      with regard to postoperative liver function and survival rate after the
      hepatectomy for HCC.

PMID- 11848541
TI  - Treatment of unresectable malignant abdominal, pelvic and thoracic tumors using
      abdominal pelvic and thoracic stop-flow chemotherapy.
AB  - BACKGROUND: Stop-flow perfusion (SFP) has been recently used to enhance the
      effects of chemotherapy in patients with locally advanced tumors. PATIENTS AND
      METHODS: Over a 2-year period we performed abdominal, pelvic and thoracic SFP in
      12 patients with unresectable or metastatic tumors, using balloon catheters
      inserted into the abdominal aorta and inferior vena cava. Blood flow was occluded
      and hypoxic extracorporeal perfusion or SFP was performed for advanced diseases.
      The chemotherapeutic agents were directly administered into the aorta and/or
      inferior vena cava for thoracic SFP. The procedure was repeated in each patient,
      with one-month interval between sessions. Haemofiltration was also applied in two
      patients with generalized abdominal disease in order to reduce systemic toxicity.
      RESULTS: At post-operative CT or MRI follow-up, tumor shrinkage of more than 50%
      was observed in six patients, while post-SFP chemotherapy surgical resection of
      the tumors became feasible in four cases. The relief of pain, wherever present,
      was dramatic in the immediate post-operative period. Overall clinical improvement
      was achieved in all 12 patients. Post-operative recovery was uneventful in all
      but two patients, who developed minor systemic toxicity. CONCLUSION: SFP appears
      to be a safe technique with low morbidity which improves the quality of life of
      cancer patients and allows satisfactory control of locally advanced tumors and
      metastatic carcinomatosis.

PMID- 11848542
TI  - Circulating IgG response to stromelysin-3, collagenase-3, galectin-3 and
      mesothelin in patients with pharynx/larynx squamous cell carcinoma.
AB  - With the aim of identifying tumor-associated antigens that could be potential
      markers and/or targets of diagnostic and/or therapeutic approaches, we studied
      the occurrence of circulating IgG antibodies to human stromelysin-3, collagenase
      3, galectin-3 and mesothelin, by Western blot against their purified recombinant
      forms, in the sera of 50 patients with pharynx/larynx squamous cell carcinoma
      (PLSCC), as well as in the sera of 50 healthy blood donors. Overall, antibodies
      to collagenase-3 were detected in 50% of all the cancer patients and 16% of the
      blood donors examined; this percentage difference was statistically significant
      (p = 0.00066). With respect to anti-galectin-3 antibodies, the percentages were
      32% and 18%, respectively, but they were not statistically different (p = 0.16).
      Low levels of antibodies to stromelysin-3 and to mesothelin were detected in sera
      from only two cancer patients. No significant correlations were found in the
      present study between the presence of antibodies to these proteins and tumor
      site, clinical and T stages, lymph node involvement, DNA ploidy and histological
      grade of differentiation of the primary tumors. To our knowledge, this is the
      first report on the detection of circulating IgG to collagenase-3 in cancer
      patients. Some of the percentages found here in certain groups of patients are
      among the highest reported of circulating antibodies to any tumor component
      studied so far. The monitoring and the use of human antibodies to collagenase-3
      could be of diagnostic and therapeutic interest.

PMID- 11848544
TI  - Whole body positron emission tomography with 18F-fluoro-2-deoxyglucose for the
      detection of recurrent ovarian cancer.
AB  - Although many cancers can be detected by whole-body positron emission tomography
      (PET) with 18F-fluoro-2-deoxyglucose (FDG), there has been limited clinical
      experience with FDG-PET for the detection of recurrent ovarian cancers.
      Therefore, the aim of this study was to evaluate the clinical value of FDG-PET in
      the detection of recurrent ovarian cancer. Whole body FDG-PET scans were
      performed on 24 women who had previous histories of ovarian cancer and treatment
      with surgery and chemotherapy. All patients also underwent physical examination,
      laboratory testing of serum CA-125 level and pelvic-abdominal-chest computed
      tomography (CT) or magnetic resonance imaging (MRI). The results of FDG-PET scans
      were correlated with serum CA-125 level, CT/MRI and operative pathology results.
      The diagnostic sensitivity was 90.9%, 90.9% and 90.9%, specificity was 92.3%,
      76.9% and 46.2% and accuracy was 91.7%, 83.3% and 66.7% for FDG-PET, serum tumor
      marker of CA-125 level and CT/MRI in detecting recurrent ovarian cancer,
      respectively. FDG-PET is a useful diagnostic tool in detecting recurrent ovarian
      cancers with high specificity as compared with the serum tumor marker CA-125
      level and the conventional CT/MRI morphological imaging methods.

PMID- 11848543
TI  - Telomerase activity in endoscopically visible lung cancer.
AB  - To examine the correlation between telomerase activity and clinical features in
      patients with lung cancer, we examined 86 patients with endoscopically visible
      lung cancer including 61 with non-small cell lung cancer (NSCLC) and 25 with
      small cell lung cancer (SCLC). Telomerase activity was detected by using
      Telomerase ELISA Kit (Bohringer Manheim, Germany). The median and interquartile
      ranges of telomerase activity in normal lung, NSCLC and SCLC were 65 and 51-75,
      106 and 58-349 and 285 and 117-2214, respectively. Normal lung, NSCLC and SCLC
      had significantly different telomerase activity (p < or = 0.0001). Between NSCLC
      and SCLC, SCLC exhibited higher telomerase activity than did NSCLC (p=0.0029). A
      cut-off level of absorbance [A450nm-A690nm] of 86 derived from 90% specificity in
      normal lung was used; sensitivity for overall lung cancer, NSCLC and SCLC was
      62.8%, 54.1% and 84.0%, respectively. There was no significant difference in
      telomerase activity between each stage in NSCLC (p=0.9243). In SCLC, however, the
      median and interquartile range of telomerase activity in extensive disease (2128
      and 292-2681) was significantly higher than those in limited disease (207 and 97
      252) (p=0.0285).

PMID- 11848545
TI  - Comparison of technetium-99m tetrofosmin and gallium-67 citrate scintigraphy for
      detecting malignant lymphoma.
AB  - The aim of this study was to compare the value of technetium-99m tetrofosmin (Tc
      TF) scintigraphy with that of gallium-67 citrate (Ga-67) scintigraphy for
      detecting malignant lymphoma. In this study, 50 patients with malignant lymphoma
      underwent Tc-TF and Ga-67 scintigraphy before receiving any therapy. Tc-TF
      scintigraphy detected malignant lymphoma in 44 (88%) patients, but was false
      negative in 4 cases of infradiaphragmatic malignant lymphoma and in 2 cases of
      malignant lymphoma with chemotherapy resistance. Ga-67 scintigraphy detected
      malignant lymphoma in 45 (90%) patients, but was false-negative in 3 cases of low
      grade non-Hodgkin's lymphoma and in 2 cases of malignant lymphoma with bone
      marrow involvement. There was no significant difference in sensitivity between Tc
      TF and Ga scintigraphy. However, a combination of Tc-TF and Ga-67 scintigraphy
      detected malignant lymphoma in all 50 patients (100%). We conclude that it is
      necessary to combine Tc-TF and Ga-67 scintigraphy to accurately detect malignant
      lymphoma.

PMID- 11848546
TI  - Delirium after interleukin-2 and alpha-interferon therapy for renal cell
      carcinoma.
AB  - A 55-year-old man receiving alpha-interferon and interleukin-2 therapy for renal
      cell carcinoma presented with seizures and delirium. A CT-scan of the cerebrum
      did not reveal any disorder. Both alpha-interferon and interleukin-2 were
      stopped. Treatment with steroids led to complete regression of central nervous
      system symptomatology. We emphasize the importance of ruling out iatrogenesis in
      patients treated with alpha-interferon and/or interleukin-2 who display
      neuropsychiatric symptoms.

PMID- 11848547
TI  - Does long-term application of granulocyte colony-stimulating factor adversely
      influence overall survival in patients with ovarian cancer? A clinical study.
AB  - The purpose of this study was to investigate the effect of long-term
      administration of G-CSF with regard to its impact on overall survival of patients
      with ovarian cancer. We report the results of a non-randomized trial on 64
      patients with advanced ovarian cancer treated with 6 cycles of conventional
      chemotherapy. Chemotherapy comprised carboplatin 400 mg/m2 and epirubicin 70
      mg/m2 on day 1 of each cycle and prednimustine 100 mg/m2 on days 3 to 7, every 28
      days. Thirty-three patients received CEP chemotherapy with G-CSF support whereas
      31 women received CEP chemotherapy alone. The schedule of G-CSF was 5 mg/kg/day
      subcutanously on days 8 to 21 of each cycle. The severity of reduction in white
      cells and neutrophil count was significantly different in the two treatment
      groups (p<0.05), with more toxicity in the non- G-CSF group. G-CSF users had a
      non significant 0.88-fold lower risk of dying from ovarian cancer (95% CI, 0.48
      1.60, p=0.678). In a survival analysis using a Cox proportional hazards model,
      residual tumor remained as an independent prognostic factor. The increasing
      amount of residual tumor resulted in a 1.767-fold higher risk (95% CI, 1.23-2.53,
      p=0.002) of death secondary to the underlying disease. In conclusion, this trial
      has failed to demonstrate any negative impact on patients' overall survival for
      the additional use of G-CSF with platinum-based chemotherapy; our results were
      consistent with the beneficial effects of G-CSF treatment on cytotoxic
      chemotherapy-induced myelosuppression.

PMID- 11848548
TI  - Sucralfate in the treatment of chemotherapy-induced stomatitis: a double-blind,
      placebo-controlled pilot study.
AB  - BACKGROUND: The study was a double-blind, placebo-controlled, randomised pilot
      study to assess the efficacy of sucralfate gel in the treatment of chemotherapy
      induced mucositis. PATIENTS AND METHODS: At the onset of stomatitis, forty
      patients received sucralfate gel (1 gr.) or placebo and were instructed to apply
      the gel over oral mucosas, 3 times daily. RESULTS: Objective response was
      observed in 14 patients (11 complete response+3 partial response) and in 15
      patients (10 CR+5 PR), in the sucralfate and placebo arms, respectively; (p =
      NS). Analysis of VAS (visual analogue scale) scoring of pain did not detect any
      statistical difference between the two groups. No important side-effects were
      observed. Twelve out 21 patients who obtained a complete resolution of stomatitis
      (5 out of 11 and 7 out of 10 in the sucralfate and in placebo arms, respectively)
      received further treatment at the subsequent course of chemotherapy; prevention
      of mucositis was observed in 4 patients in the sucralfate arm and in 6 patients
      in the placebo arm, respectively. CONCLUSION: In the present pilot study,
      sucralfate did not demonstrate a significant advantage in comparison to the
      placebo in the treatment of chemotherapy-induced stomatitis.

PMID- 11848549
TI  - Diffuse submucosal cysts of the stomach associated with gastric cancer:
      contribution of Helicobacter pylori infections.
AB  - Diffuse submucosal cysts (DSCs) in the stomach are often associated with gastric
      cancer and a high occurrence of multiple gastric cancers. We studied the
      clinicopathological features of four early gastric cancer patients with DSCs in
      the submucosal layer of the stomach. All patients had early gastric cancers with
      gastritis and erosion in the gastric mucosa, and were positive for Helicobacter
      pylori (H. pylori). Based on a review of the reported cases, we found that a very
      high proportion (>94%) of DSCs are associated with infection by H. pylori.
      Although DSCs have previously been considered to be paracancerous lesions of
      gastric cancer, we speculate that DSCs might be post-inflammatory changes
      following infection by H. pylori, which may result in the high incidence of
      gastric cancer development.

PMID- 11848550
TI  - Free to complexed PSA ratio in differentiating benign prostate hyperplasia from
      prostate cancer.
AB  - BACKGROUND: The description of the different forms of circulating PSA has opened
      a new strategy in the diagnosis of prostate cancer. The aim of our study was to
      assess the diagnostic potential of PSA and the PSA fractions in the diagnosis of
      benign prostate hyperplasia (BPH) and prostate cancer. PATIENTS AND METHODS: We
      measured the serum levels of PSA (Elecsys 2010, Roche Diagnostics, Mannheim,
      Germany), complexed PSA (Immuno 1 system, Bayer, Tarrytown, NY USA) and free PSA
      (Elecsys 2010, Roche Diagnostics, Mannheim, Germany) in 178 patients with BPH and
      44 patients with prostate cancer. RESULTS: ROC curves were used for comparison of
      the diagnostic utility of the tests assessed. The biggest areas under the curve
      were obtained for the ratios between free/complexed PSA and free/total PSA (0.887
      and 0.872, respectively). When choosing the cut-off values to obtain a 90%
      sensibility, we found that the specificity for the free/total PSA ratio was 59%
      and for the free/complexed PSA ratio 72%. CONCLUSION: Our results suggest that
      replacement of the measurement of total PSA by complexed PSA in prostate cancer
      diagnosis may be interesting. Nevertheless, as this is a retrospective study
      limited to a small number of patients, it is obvious that we need more data to
      make a final decision with regard to this subject.

PMID- 11848551
TI  - Pathologic features of endometrial carcinoma in elderly women.
AB  - It has been estimated that more than two-thirds of cancers occur in people over
      65 years of age: endometrial cancer (EC) is the most common gynaecologic cancer
      in the U.S. and represents the fourth most common malignancy in women. Some
      authors have reported that EC in elderly women was more aggressive,
      histologically less-differentiated and often non-endometrioid when compared with
      EC in the younger population. The purpose of this retrospective study is to
      evaluate the pathologic features of EC in women 70 years old or over compared
      with those of younger patients. Between 1987 and 1997, 174 patients with EC were
      surgically treated: 52 women were 70 years old or over. Two-thirds of both groups
      had surgical Stage I tumors: 54% of surgical Stage I tumors in the elderly had
      myometrial invasion more than 50% compared with 32% in the younger group
      (p<0.01). On the whole 37% of elderly patients had Stage IC tumors compared with
      21% in younger women (p<0.01). Seventy-five percent of elderly women had Grade 2
      or 3 tumors compared with 55% of younger patients (p<0.005). The majority of EC
      was endometrioid in both groups: 8% of elderly patients had clear-cell carcinomas
      compared with 4% of younger women (p not significant). No elderly patients showed
      nodal metastasis (0 out of 10): 9% of younger women had pelvic or para-aortic
      metastasis. The median follow-up was 78 months. The overall survival in the
      elderly and in the younger group was 80% and 93%, respectively (p<0.01): in
      elderly women overall survival significantly varied according to histotype and
      depth of myometrial invasion in Stage I tumors. In conclusion patients 70 years
      old or over have a high probability of surgical Stage I EC but a significantly
      higher probability of deep myometrial invasion and less-differentiated tumors
      than younger women: the prognosis w as good but poorer than for younger patients.

PMID- 11848552
TI  - Lipiodol avidity of hepatic breast carcinoma metastases.
AB  - Lipiodol is taken up by hepatocellular carcinomas and is used for diagnosis and
      therapy. This is the first report of lipiodol uptake by liver metastases from
      breast cancer.

PMID- 11848553
TI  - Stage IV ovarian cancer: prognostic factors and survival beyond 5 years.
AB  - BACKGROUND: Ovarian cancer continues to be the leading cause of death due to
      gynecologic malignancies and most patients still present with advanced disease.
      In the present study we evaluated long-term survival and prognostic factors in
      patients with stage IV ovarian cancer. PATIENTS AND METHODS: The charts of 62
      consecutive women with FIGO stage IV epithelial ovarian cancer were reviewed.
      RESULTS: Chemotherapy was the only factor associated with longer survival. Three
      patients (5%) survived for longer than 5 years. One died of disease at 6.3 years
      and two are alive without evidence of disease at 12.4 and 14.9 years,
      respectively. CONCLUSION: Survival seemed to correlate with the possibility of
      administering chemotherapy. Patients with verified stage IV ovarian cancer, in
      whom due to the initial tumor load, operative extent and concomitant illness, the
      possibility of postoperative chemotherapy administration seems questionable,
      might be considered for primary chemotherapy followed by surgery.

PMID- 11848554
TI  - Differentiation of viable and dead Escherichia coli O157:H7 cells on and in apple
      structures and tissues following chlorine treatment.
AB  - Confocal scanning laser microscopy (CSLM) was used to differentiate viable and
      nonviable cells of Escherichia coli O157:H7 on and in raw apple tissues following
      treatment with water and 200 or 2,000 ppm active chlorine solution. Whole unwaxed
      Red Delicious cultivar apples at 25 degrees C were inoculated by dipping in a
      suspension of E. coli O157:H7 (8.48 log10 CFU/ml) at 4 degrees C, followed by
      treatment in water or chlorine solution at 21 degrees C for 2 min. The dead cells
      on and in apples were distinguished from live cells by treating tissue samples
      with SYTOX green nucleic acid stain. Viable and dead cells were then labeled with
      an antibody conjugated with a fluorescent dye (Alexa Fluor 594). The percentage
      of viable cells on the apple surface, as well as at various depths in surface and
      internal structures, was determined. The mean percentages of viable cells located
      at the sites after treatment with water or chlorinated water were in the
      following order, which also reflects the order of protection against
      inactivation: floral tube wall (20.5%) > lenticels (15.0%) > damaged cuticle
      surrounding puncture wounds (13.0%) > intact cuticle (8.1%). The location of
      viable cells within tissues was dependent on the structure. Except for lenticels,
      the percentage of viable cells increased as depth into the CSLM stacks increased,
      indicating that cells attached to subsurface structures were better protected
      against inactivation with chlorine than were cells located on exposed surfaces.
      Further research is warranted to investigate the efficacy of other chemical
      sanitizers. as well as that of surfactants and solvents in combination with
      sanitizers, in removing or killing E. coli O157:H7 lodgedin protective structures
      on the surface and within tissues of apples.

PMID- 11848555
TI  - Influence of acid adaptation on the tolerance of Escherichia coli O157:H7 to some
      subsequent stresses.
AB  - Three stains of Escherichia coli O157:H7, including ATCC 43889, ATCC 43895, and
      933, were first subjected to acid adaptation at a pH of 5.0 for 4 h. Thermal
      tolerance at 52 degrees C and survival of the acid-adapted as well as the
      nonadapted cells of E. coli O157:H7 in the presence of 10% sodium chloride, 0.85%
      bile salt, or 15.0% ethanol were investigated. Results showed that the effect of
      acid adaptation on the survival of E. coli O157:H7 varied with the strains and
      types of subsequent stress. Acid adaptation caused an increase in the thermal
      tolerance of E. coli O157:H7 ATCC 43889 and ATCC 43895, but no significant
      difference in the thermal tolerance was noted between acid-adapted and nonadapted
      cells of E. coli O157:H7 933. Although the magnitude of increase varied with
      strains of test organisms, acid adaptation generally led to an increase in the
      tolerance of E. coli O157:H7 to sodium chloride. On the other hand, the
      susceptibility of acid-adapted cells of the three strains of E. coli O157:H7
      tested did not show a significant difference from that of their nonadapted
      counterparts when stressed with bile salt. The acid-adapted cells of E. coli
      O157:H7 ATCC 43889 and ATCC 43895 were less tolerant than the nonadapted cells to
      ethanol, whereas the tolerance of adapted and nonadapted cells of E. coli O157:H7
      933 showed no significant differences.

PMID- 11848556
TI  - A multiplex polymerase chain reaction for the differentiation of Campylobacter
      jejuni and Campylobacter coli from a swine processing facility and
      characterization of isolates by pulsed-field gel electrophoresis and antibiotic
      resistance profiles.
AB  - A multiplex polymerase chain reaction (PCR) was developed for the detection and
      speciation of 60 Campylobacter strains isolated from porcine rectal swabs and
      from different areas in a pork processing plant. The PCR assay was based on
      primers specific for the cadF gene of pathogenic Campylobacter species, a
      specific but undefined gene of Campylobacter jejuni, and the ceuE gene of
      Campylobacter coli. Further characterization of these isolates was established by
      pulsed-field gel electrophoresis (PFGE) analyses with the restriction
      endonuclease SmaI. In addition to molecular discrimination, the antibiotic
      resistance profiles of the isolates were examined by the Kirby Bauer disc
      diffusion method with 22 antibiotics. Differentiation of isolates by multiplex
      PCR identified 86.9% (52 of 60) as C. coli and 13.1% (8 of 60) as C. jejuni.
      Using the Molecular Analyst software, 60 PFGE types were identified. The
      percentages of relatedness among C. jejuni strains with PFGE ranged from 25 to
      86%, while those among C. coli strains ranged from 34 to 99%. Among the 60 PFGE
      types, each of 12 C. coli isolates showed > or =90% similarity to one other
      isolate. The antibiotic resistance profiles of all 60 isolates were distinct.
      Analyses of antibiotic resistance profiles showed that all isolates were
      resistant to five or more antibiotics. Twenty-five percent (2 of 8) of C. jejuni
      isolates and 15% (8 of 52) of C. coli isolates were resistant to at least one of
      the three fluoroquinolones tested, antibiotics that are commonly used in the
      treatment of human Campylobacter infections. Three percent (2 of 60) of
      Campylobacter isolates examined were resistant to all three fluoroquinolones. On
      the basis of the PFGE and antibiotic resistance profiles, each of the 60 isolates
      was distinct, suggesting that C. jejuni and C. coli strains originating from
      diverse sources were present in porcine samples and in the pork processing plant.

PMID- 11848557
TI  - Survival of Salmonella on tomatoes stored at high relative humidity, in soil, and
      on tomatoes in contact with soil.
AB  - Salmonellosis has been linked to the consumption of several types of raw fruits
      and vegetables, some of which may have been contaminated with Salmonella before
      harvesting. The objectives of this study were to investigate water and soil as
      reservoirs of Salmonella for the contamination of mature green tomato fruits.
      Salmonella survived for at least 45 days in inoculated moist soil. The population
      of Salmonella on tomatoes in contact with soil increased by 2.5 log10 CFU per
      tomato during storage for 4 days at 20 degrees C and remained constant for an
      additional 10 days. The number of cells inoculated on tomatoes decreased by
      approximately 4 log10 CFU per tomato during storage for 14 days at 20 degrees C
      and 70% relative humidity. Fruits in contact with inoculated soil for 1 day at 20
      degrees C harbored Salmonella only near or on the skin surface. More Salmonella
      cells were observed in stem scar and subsurface areas of tomatoes as the time of
      storage increased. PCR fingerprinting revealed that among five Salmonella
      serotypes in the inoculum, Salmonella Montevideo was the most persistent on
      tomatoes in contact with inoculated soil and on spot-inoculated tomatoes,
      followed by Salmonella Poona and Salmonella Michigan. The results of this study
      demonstrate that an enhanced green fluorescent protein marker can be used to
      detect cells and monitor the growth of Salmonella in the presence of other
      microorganisms. Observations on the infiltration of Salmonella into tomato
      tissues support the contention that preharvest contact of produce with
      contaminated water or soil exacerbates problems associated with the postharvest
      removal of pathogens or their accessibility to treatment with sanitizers.

PMID- 11848558
TI  - Effects of the transportation of beef cattle from the feedyard to the packing
      plant on prevalence levels of Escherichia coli O157 and Salmonella spp.
AB  - Two hundred steers and heifers from a large feedyard (65,000-head capacity) were
      used to determine the prevalence levels of enterohemorrhagic Escherichia coli
      O157 (EHEC O157) and Salmonella spp. prior to and after shipping to a commercial
      packing facility. Two samples, a ventral midline hide swab and a fecal sample,
      were aseptically collected from each animal 2 weeks prior to the date of
      transportation and at the packing plant immediately after exsanguination. Samples
      were collected from all trailers (n = 46) before animals were loaded for
      transport to the packing facility. The average prevalence levels of EHEC O157 on
      hides (18%) and in feces (9.5%) at the feedyard decreased (P > 0.05) at the
      packing plant to 4.5 and 5.5%, respectively. The average prevalence levels of
      Salmonella spp. on hides (6%) and in feces (18%) at the feedyard increased to 89
      and 46%, respectively, upon arrival at the packing plant. Average prevalence
      levels for EHEC O157 and Salmonella spp. on the trailers were 5.43 and 59%,
      respectively. The results of this study demonstrate that transportation may be a
      potential stressor for cattle, as evidenced by the increased shedding of
      Salmonella spp.

PMID- 11848559
TI  - Prevalence and antibiotic susceptibility of Salmonella isolated from beef animal
      hides and carcasses.
AB  - This study determined the prevalence of Salmonella on beef animal hides and
      carcasses and antimicrobial susceptibility profiles against a panel of 13
      antibiotics. In each of the eight commercial packing facilities, of which five
      processed primarily heifers and steers and the remaining three processed
      primarily cows and bulls, hide and carcass sponge swab samples were obtained
      immediately before hide removal and before carcass chilling, respectively.
      Overall, prevalence of Salmonella on external surfaces (hides) of cattle was
      15.4% (49 of 319), whereas prevalence after dehiding and other
      slaughtering/dressing processes, including the application of decontamination
      treatments, was, as expected, reduced (P < 0.05) to 1.3% (4 of 320) on carcass
      surfaces. From 53 total Salmonella-positive hide and carcass samples, 526
      biochemically confirmed isolates were obtained to determine antimicrobial
      susceptibility profiles. Of 53 Salmonella-positive samples, individually, 24
      (45.3%), 17 (32.1%), 17 (32.1%), 11 (20.8%), 8 (15.1%), 8 (15.1%), 8 (15.1%), 4
      (7.5%), and 2 (3.8%) samples yielded at least one isolate resistant to
      amoxicillin/clavulanic acid, tetracycline, streptomycin, sulfonamides,
      ampicillin, ampicillin/sulbactam, chloramphenicol, gentamicin, and
      trimethoprim/sulfamethoxazole, respectively. None of the Salmonella-positive
      samples yielded an isolate resistant to ceftriaxone, ciprofloxacin, enrofloxacin,
      or levofloxacin. Although none of the samples yielded an isolate simultaneously
      resistant to three or four antimicrobials, a total of eight samples yielded at
      least one isolate resistant to five or more antimicrobials tested. Included among
      the 18 group B-positive samples were three samples that, individually, yielded at
      least one Salmonella Typhimurium var. Copenhagen DT104 isolate resistant to at
      least six antimicrobials tested. Results from this study support current prudent
      therapeutic and subtherapeutic antimicrobial use recommendations.

PMID- 11848560
TI  - Survival and growth of alkali-stressed Listeria monocytogenes on beef
      frankfurters and thermotolerance in frankfurter exudates.
AB  - Cells of Listeria monocytogenes exposed at 4 degrees C to 1% solutions of two
      alkaline cleaners or alkali-adapted in tryptose phosphate broth (pH 10.0) at 37
      degrees C for 45 min, followed by 4 degrees C for 48 h, were inoculated onto beef
      frankfurters containing high fat (16 g) and high sodium (550 mg) or low fat (8 g)
      and low sodium (250 mg) per 57-g serving. Frankfurters were surface inoculated
      (2.0 log10 CFU/g), vacuum packaged, stored at -20, 4, or 12 degrees C, and
      analyzed for populations of L. monocytogenes at 2-day to 2-week intervals.
      Populations did not change significantly on frankfurters stored at -20 degrees C
      for up to 12 weeks. After storage at 4 degrees C for 6 weeks (I week before the
      end of shelf life), populations of control cells and cells exposed to alkaline
      cleaners were ca. 6.0 log10 CFU/g of low fat, low sodium (LFLS) frankfurters and
      ca. 3.5 log10 CFU/g of high fat, high sodium (HFHS) frankfurters. Growth of
      alkali-adapted cells on both types of frankfurters was retarded at 4 degrees C.
      Growth of L. monocytogenes on frankfurters stored at 12 degrees C was more rapid
      than at 4 degrees C, but a delay in growth of alkali-adapted cells on HFHS and
      LFLS frankfurters was evident during the first 9 and 6 days, respectively. Alkali
      adapted cells had a significantly (P < or = 0.05) lower logistic D59 degrees C
      value (decimal reduction time) than alkaline cleaner-exposed cells, but the D59
      degrees C-value was not different from that of control cells. Cells exposed to a
      nonbutyl alkaline cleaner, and then heated in LFLS frankfurter exudates, had a
      significantly lower D62 degrees C-value than cells that had been exposed to some
      of the other treatments. Growth characteristics of L. monocytogenes inoculated
      onto the surface of frankfurters may be altered by previous exposure to alkaline
      environments. Differences in growth characteristics of L. monocytogenes on HFHS
      versus LFLS beef frankfurters stored at refrigeration temperatures indicate that
      composition influences the behavior of both alkaline-stressed and control cells.

PMID- 11848561
TI  - Control of Listeria monocytogenes with combined antimicrobials after postprocess
      contamination and extended storage of frankfurters at 4 degrees C in vacuum
      packages.
AB  - Contamination of ready-to-eat foods, such as frankfurters, with Listeria
      monocytogenes, is a major concern that needs to be addressed in order to enhance
      the safety of these products. The objective of this study was to determine the
      effectiveness of combinations of antimicrobials included in the formulation of
      frankfurters against L. monocytogenes inoculated (10(3) to 10(4) CFU/cm2) on
      their surface after peeling and before vacuum packaging. In addition, the
      antilisterial effect of immersing the packaged products, prepared with or without
      antimicrobials, in hot (75 or 80 degrees C) water for 30 to 90 s was evaluated.
      Samples were stored at 4 degrees C for up to 120 days and periodically analyzed
      for pH and for microbial growth on tryptic soy agar plus 0.6% yeast extract
      (TSAYE) and PALCAM agar. Sodium lactate (1.8%; 3% of a 60% commercial solution)
      used alone inhibited growth of L. monocytogenes for 35 to 50 days, whereas when
      used in combination with 0.25% sodium acetate, sodium diacetate, or glucono-delta
      lactone (GDL), sodium lactate inhibited growth throughout storage (120 days).
      Immersing packaged frankfurters in hot water (80 degrees C, 60 s) reduced
      inoculated populations of L. monocytogenes by 0.4 to 0.9 log CFU/cm2 and reduced
      its growth by 1.1 to 1.4 log CFU/cm2 at 50 to 70 days of storage in samples
      containing 1.8% sodium lactate alone. However, immersion of frankfurters
      containing no antimicrobials in hot water (75 or 80 degrees C) did not inhibit
      growth of the pathogen for more than 10 to 20 days, unless one frankfurter was
      placed per bag and heat treated for 90 s. These results indicate that the
      inclusion of 1.8% sodium lactate with 0.25% sodium acetate, sodium diacetate, or
      GDL in cured meat formulations may control L. monocytogenes growth during
      refrigerated (4 degrees C) storage. Additional studies are required to evaluate
      the effects of these combinations at abusive temperatures of storage, as well as
      on additional processed meat formulations and on the sensory quality and shelf
      life of products.

PMID- 11848562
TI  - Competitive inhibition of Listeria monocytogenes in ready-to-eat meat products by
      lactic acid bacteria.
AB  - Forty-nine strains of lactic acid bacteria (LAB), isolated from commercially
      available ready-to-eat (RTE) meat products, were screened for their ability to
      inhibit the growth of Listeria monocytogenes at refrigeration (5 degrees C)
      temperatures on agar spot tests. The three most inhibitory strains were
      identified as Pediococcus acidilactici, Lactobacillus casei, and Lactobacillus
      paracasei by 16S rDNA sequence analysis. Their antilisterial activity was
      quantified in associative cultures in deMan Rogosa Sharpe (MRS) broth at 5
      degrees C for 28 days, resulting in a pathogen reduction of 3.5 log10 cycles
      compared to its initial level. A combined culture of these strains was added to
      frankfurters and cooked ham coinoculated with L. monocytogenes, vacuum packaged,
      and stored at 5 degrees C for 28 days. Bacteriostatic activity was observed in
      cooked ham, whereas bactericidal activity was observed in frankfurters. Numbers
      of L. monocytogenes were 4.2 to 4.7 log10 and 2.6 log10 cycles lower than
      controls in frankfurters and cooked ham, respectively, after the 28-day
      refrigerated storage. In all cases, numbers of LAB increased by only 1 log10
      cycle. The strain identified as P. acidilactici was possibly a bacteriocin
      producer, whereas the antilisterial activity of the other two strains was due to
      the production of organic acids. There was no significant difference (P > 0.05)
      in the antilisterial activity detected in frankfurters whether the LAB strains
      were used individually or as combined cultures. Further studies over a 56-day
      period indicated no impact on the quality of the product. This method represents
      a potential antilisterial intervention in RTE meats, because it inhibited the
      growth of the pathogen at refrigeration temperatures without causing sensory
      changes.

PMID- 11848563
TI  - Effect of nitrogen gas packaging on the quality and microbial growth of fresh-cut
      vegetables under low temperatures.
AB  - Nitrogen (N2) gas packaging for fresh-cut vegetables (lettuce and cabbage) has
      been examined as a means of modified atmosphere packaging (MAP) for extending the
      shelf life of cut vegetables. Gas composition in enclosed packages that contained
      cut vegetables and were filled with 100% N2 had an oxygen (O2) concentration of
      1.2 to 5.0% and a carbon dioxide (CO2) concentration of 0.5 to 3.5% after 5 days
      of storage. An atmosphere of low concentrations of O2 and high CO2 conditions
      occurred naturally in the package filled with N2 gas. Degradation of cut
      vegetables in terms of appearance was delayed by N2 gas packaging. Because of
      this effect, the appearance of fresh-cut vegetables packaged with N2 gas remained
      acceptable at temperatures below 5 degrees C after 5 days. Treatment with acidic
      electrolyzed water (AcEW) contributed to the acceptability of the vegetables'
      appearance at 5 and 10 degrees C in the air-packaging system. N2 gas packaging
      did not significantly affect the growth of microbial populations (total aerobic
      bacteria, coliform bacteria, Bacillus cereus, and psychrotrophic bacteria) in or
      on cut vegetables at 1, 5, and 10 degrees C for 5 days. Microbial growth in or on
      the cut vegetables was inhibited at 1 degrees C for 5 days regardless of
      atmospheric conditions.

PMID- 11848564
TI  - Growth of Carnobacterium divergens V41 and production of biogenic amines and
      divercin V41 in sterile cold-smoked salmon extract at varying temperatures, NaCl
      levels, and glucose concentrations.
AB  - A complete factorial design 2(3) was used to study some aspects of Carnobacterium
      divergens V41 metabolism (growth, biogenic amine production, and divercin V41
      production) in sterile cold-smoked salmon extract (SSE) at varying temperatures
      (3 to 9 degrees C), NaCl levels (2.5 to 6.5%), and glucose concentrations (2 to 6
      g liter(-1)). The results showed that temperature and NaCl content were the most
      influential factors on growth parameters in SSE. Predictive models are suggested
      for the assessment of C. divergens lag time (t(lag)) and maximum specific growth
      rate (micro(max)) Among the biogenic amines studied, only tyramine was found to
      be produced by C. divergens in SSE. Furthermore, we showed that temperature,
      NaCl, and glucose variations did not greatly affect tyramine and divercin V41
      production by the bacteria under the experimental conditions used. Indeed,
      divercin V41, a bacteriocin from C. divergens V41 that is highly active against
      some Listeria strains, was produced in SSE even under harsh culture conditions.
      Similarly, tyramine production in SSE was delayed at 3 degrees C but reached 35
      microg ml(-1) in all experiments after 27 days of storage. However, this final
      tyramine concentration in SSE is low compared with the threshold values of 100 to
      800 microg g(-1) reported as the potentially toxic dose in foods. Thus, we have
      found that C. divergens V41 is a promising strain for the biopreservation of
      refrigerated cold-smoked salmon.

PMID- 11848565
TI  - Evaluation of the spiral plating method for the enumeration of microorganisms
      throughout the manufacturing and ripening of a raw goat's milk cheese.
AB  - A statistical comparison of the spiral plate count (SPLPC) and the standard plate
      count (SPC) methods for enumeration of microorganisms in raw goat's milk cheese
      throughout its manufacturing and ripening was carried out. Enumeration of
      mesophiles, lactic acid bacteria (presumptive lactococci, presumptive
      leuconostocs, and presumptive lactobacilli), Micrococcaceae, Enterobacteriaceae,
      and molds and yeasts was carried out for milk, curd, and 2-, 5-, 10-, 17-, and 27
      day-old cheeses. Average counts for the SPLPC and SPC methods differed by less
      than half of a log cycle for all microbial groups studied (range of difference, 
      0.1386 [mesophiles] to +0.4397 [presumptive lactobacilli]). The results of the
      SPLPC method compared favorably with the results of the SPC procedure for
      mesophiles, presumptive lactococci, presumptive leuconostocs, Enterobacteriaceae,
      and molds and yeasts (the variance between replicate platings was close to 0.005,
      and correlation coefficients were >0.9). Correlation coefficients were lower for
      Micrococcaceae (r = 0.824) and presumptive lactobacilli (r = 0.670). Analysis of
      variance showed that the plating method was a significant factor (P < 0.05) for
      presumptive lactobacilli counts. In general, results from the SPLPC method
      compared favorably with results from SPC procedure in the enumeration of
      microorganisms in goat cheese throughout its manufacturingand ripening processes.
      However, the suitability of the SPLPC method depends mainly on the microbial
      group studied.

PMID- 11848566
TI  - Inactivation of foodborne pathogens in milk using dynamic high pressure.
AB  - Improving the microbiological safety of perishable foods is currently a major
      preoccupation in the food industry. The aim of this study was to investigate the
      inactivation of three major food pathogens (Listeria monocytogenes [LSD 105-1],
      Escherichia coli O157:H7 [ATCC 35150], and Salmonella enterica serotype
      Enteritidis ATCC [13047]) by dynamic high pressure (DHP) in order to evaluate its
      potential as a new alternative for the cold pasteurization of milk. The
      effectiveness of DHP treatment against L. monocYtogenes, E. coli O157:H7, and
      Salmonella Enteritidis was first evaluated in 0.01 M phosphate-buffered saline
      (PBS) at pH 7.2 as a function of applied pressure (100, 200, and 300 MPa) and of
      the number of passes (1, 3, and 5) at 25 degrees C. A single pass at 100 MPa
      produced no significant inactivation of the three pathogens, while increasing the
      pressure up to 300 MPa or the number of passes to five increased inactivation.
      From an initial count of 8.3 log CFU/ml, complete inactivation of viable L.
      monocytogenes was achieved after three successive passes at 300 MPa, while 200
      MPa treatments with three and five passes completely eliminated viable Salmonella
      Enteritidis and E. coli O157:H7, respectively. The effectiveness of DHP for the
      inactivation of these pathogens was compared to that of hydrostatic high pressure
      (HHP) using the same pressure (200 MPa, single pass at 25 degrees C). In general,
      two additional log reductions in viable count were obtained with DHP DHP was less
      effective against L. monocytogenes and E. coli O157:H7 in raw milk than in PBS.
      After five passes at 200 MPa, an 8.3-log reduction was obtained for E. coli
      O157:H7, while a reduction of about 5.8 log CFU/ml was obtained for L.
      monocytogenes exposed to 300 MPa for five passes. Exposing milk or buffer samples
      to mild heating (45 to 60 degrees C) prior to dynamic pressurization enhanced the
      lethal effect of DHP The inactivation of pathogens also depended on the initial
      bacterial concentration. The highest reduction was obtained when the bacterial
      load did not exceed 10(5) CFU/ml. In conclusion, DHP was shown to be very
      effective for the destruction of the tested pathogens. It offers a promising
      alternative for the cold pasteurization of milk and possibly other liquid foods.

PMID- 11848567
TI  - Anchovy shelf life as affected by different chilling methods during distribution.
AB  - Anchovies are a very labile fish and deteriorate fast under chilling conditions.
      In the South of Spain, fishing boats land their catches in wooden boxes with ice
      (12 to 14 kg). For some years now, fish processors have prepared this species for
      market distribution by placing about 7 kg fish in expanded polystyrene (EPS)
      boxes containing water and ice. Then, in the distribution market, boxes are
      dewatered and re-iced. Transportation of the fish in EPS boxes containing water
      and ice was recently forbidden on the grounds that boxes for transportation of
      fish in ice must have holes to let melted ice drain away. In this paper, the
      effect of preserving the anchovy in water and ice from landing to the
      distribution market was studied and compared with the more traditional methods of
      storing the fish in ice in either wooden or EPS boxes. Physical, chemical,
      microbiological, and sensory analyses were carried out over three different
      storage trials to account for the effect of seasonality. Little differences were
      found among lots, but some of the parameters showed that fish transported in
      water and ice did present less spoilage than fish stored in ice, especially when
      compared to the wooden boxes. According to these results, chilling of this fish
      in water and ice can be used as an alternative preserving method during
      transport.

PMID- 11848568
TI  - Identification of cow's milk in "buffalo" cheese by duplex polymerase chain
      reaction.
AB  - A duplex polymerase chain reaction (PCR) was developed to identify the milk of
      bovine and buffalo species in cheese products, particularly in mozzarella cheese,
      a typical Italian cheese made from buffalo's milk. Two sets of primers were
      designed on the basis of the alignment of the sequence codifying mitochondrial
      cyt b available in the GenBank database. The primers proved to be species
      specific, giving rise to 279-bp (bovine) and 192-bp (buffalo) amplified
      fragments. Since the amplification conditions for bovine and buffalo primers were
      identical, a duplex PCR was successfully applied to identify the two species in a
      single reaction step. This technique, when used to test cheese products from the
      retail trade, allowed the detection of partial or even total substitution of
      cow's milk for buffalo's milk, in some cases in samples of cheese misleadingly
      labeled "pure buffalo" mozzarella.

PMID- 11848569
TI  - A risk-based restaurant inspection system in Los Angeles County.
AB  - The majority of local health departments perform routine restaurant inspections.
      In Los Angeles County (LAC), California, approximately $10 million/year is spent
      on restaurant inspections. However, data are limited as to whether or not certain
      characteristics of restaurants make them more likely to be associated with
      foodborne incident reports. We used data from the LAC Environmental Health
      Management Information System (EHMIS), which records the results of all routine
      restaurant inspections as well as data regarding all consumer-generated foodborne
      incidents that led to a special restaurant inspection by a sanitarian
      (investigated foodborne incidents [IFBIs]). We analyzed a cohort of 10,267
      restaurants inspected from 1 July 1997 to 15 November 1997. We defined a "case
      restaurant" as any restaurant with a routine inspection from 1 July 1997 to 15
      November 1997 and a subsequent IFBI from 1 July 1997 to 30 June 1998. Noncase
      restaurants did not have an IFBI from I July 1997 to 30 June 1998. We looked for
      specific characteristics of restaurants that might be associated with the
      restaurant subsequently having an IFBI, including the size of restaurant
      (assessed by number of seats), any previous IFBIs, the overall inspection score,
      and a set of 38 violation codes. We identified 158 case restaurants and 10,109
      noncase restaurants. In univariate analysis, middle-sized restaurants (61 to 150
      seats; n = 1,681) were 2.8 times (95% confidence interval [CI] = 2.0 to 4.0) and
      large restaurants (>150 seats; n = 621) were 4.6 times (95% CI = 3.0 to 7.0) more
      likely than small restaurants (< or =60 seats; n = 7,965) to become case
      restaurants. In addition, the likelihood of a restaurant becoming a case
      restaurant increased as the number of IFBIs in the prior year increased (chi2 for
      linear trend, P value = 0.0005). Other factors significantly associated with the
      occurrence of an IFBI included a lower overall inspection score, the incorrect
      storage of food, the reuse of food, the lack of employee hand washing, the lack
      of thermometers, and the presence of any food protection violation. In
      multivariate analysis, the size of restaurant, the incorrect storage of food, the
      reuse of food, and the presence of any food protection violation remained
      significant predictors for becoming a case restaurant. Our data suggest that
      routine restaurant inspections should concentrate on those establishments that
      have a large seating capacity or a poor inspection history. Evaluation of
      inspection data bases in individual local health departments and translation of
      those findings into inspection guidelines could lead to an increased efficiency
      and perhaps cost-effectiveness of local inspection programs.

PMID- 11848570
TI  - Toxicity of fumonisin from Fusarium verticillioides culture material and
      moniliformin from Fusarium fujikuroi culture material when fed singly and in
      combination to growing barrows.
AB  - The effects of fumonisin B1 (FB1) from Fasarium verticillioides culture material
      and moniliformin from Fusarum fujikuroi culture material on growing barrows were
      evaluated. Four groups of six barrows (three replicates of two each; mean body
      weight, 11.1 kg) were fed diets containing 0 mg of FB1 and 0 mg of moniliformin
      per kg of feed (control), 100 mg of FB1 per kg of feed, 100 mg of moniliformin
      per kg of feed, and 100 mg of FB1 plus 100 mg of moniliformin per kg of feed.
      Barrows were fed these diets for 28 days. Body weight gain, feed efficiency,
      serum biochemical analytes, and hematological values were adversely affected by
      the FB1 and the FB1-plus-moniliformin diets. The moniliformin diet decreased body
      weight gain. Two barrows in the moniliformin diet group died, and two barrows in
      the FB1-plus-moniliformin diet group died. All deaths occurred during the first 6
      days of the study. Mild to moderate lesions were observed microscopically in
      heart and lung tissues of the groups fed moniliformin and FB1 plus moniliformin
      and in liver tissues of the groups fed FB1 and FB1 plus moniliformin. Except for
      the acute mortality associated with the two diets containing moniliformin.
      clinical disease induced by the combined feeding of these two mycotoxins appears
      to be additive or less than additive and due primarily to the toxic expression of
      FB1.

PMID- 11848571
TI  - Detection of protozoan parasites and microsporidia in irrigation waters used for
      crop production.
AB  - The occurrence of human pathogenic parasites in irrigation waters used for food
      crops traditionally eaten raw was investigated. The polymerase chain reaction was
      used to detect human pathogenic microsporidia in irrigation waters from the
      United States and several Central American countries. In addition, the occurrence
      of both Cryptosporidium oocysts and Giardia cysts was determined by
      immunofluorescent techniques. Twenty-eight percent of the irrigation water
      samples tested positive for microsporidia, 60% tested positive for Giardia cysts,
      and 36% tested positive for Cryptosporidium oocysts. The average concentrations
      in samples from Central America containing Giardia cysts and Cryptosporidium
      oocysts were 559 cysts and 227 oocysts per 100 liters. In samples from the United
      States, averages of 25 Giardia cysts per 100 liters and <19 (average detection
      limit) Cryptosporidium oocysts per 100 liters were detected. Two of the samples
      that were positive for microsporidia were sequenced, and subsequent database
      homology comparisons allowed the presumptive identification of two human
      pathogenic species, Encephalitozoon intestinalis (94% homology) and Pleistophora
      spp. (89% homology). The presence of human pathogenic parasites in irrigation
      waters used in the production of crops traditionally consumed raw suggests that
      there may be a risk of infection to consumers who come in contact with or eat
      these products.

PMID- 11848572
TI  - Anisakis simplex larva killed by high-hydrostatic-pressure processing.
AB  - Anisakis simplex is a common nematode parasite present in many marine fish,
      including finfish and squid. It can pose a public health problem if it is not
      destroyed during food processing. Anisakis larvae were isolated from fish tissue,
      and their survival of high-pressure treatments in distilled water and
      physiological isotonic solution was assayed. Treatment at a pressure of 200 MPa
      for 10 min at a temperature between 0 and 15 degrees C kills all Anisakis larvae,
      with a lack of motility being used as an indicator of larval death. Lower
      pressures can be successfully employed down to 140 MPa, but with lower pressures,
      the treatment time must be increased by up to I h to kill all larvae. Meanwhile,
      most larvae treated for >10 min at pressures of >120 MPa were dead, with the
      autofluorescence method being used to determine death. Cycles of compression and
      decompression increase the destruction of larvae compared with a single pressure
      treatment for a similar treatment time. Our results indicate that high-pressure
      treatment is an alternative nonthermal method for killing this nematode. The
      possible mechanism of death and damage by pressure is discussed, and uses for
      this treatment in food processing are suggested.

PMID- 11848573
TI  - Identification of tetrodotoxin and fish species in a dried dressed fish fillet
      implicated in food poisoning.
AB  - There were five victims of neurotoxic food poisoning from a dried dressed fish
      fillet in Changhua County, Taiwan, in February 2000. The toxicity of the dried
      dressed fish fillets was 243 mouse units per g according to a tetrodotoxin
      bioassay. The partially purified toxin was identified as tetrodotoxin and
      anhydrotetrodotoxin. The sequence of the 376-nucleotide region in the cytochrome
      b gene of the mitochondrial DNA exhibited the same genotype as that of the toxic
      puffer fish Lagocephalus lunaris. The same single restriction site for Hinfl was
      found in the polymerase chain reaction (PCR) products from the dried dressed fish
      fillet and the muscle of L. lunaris, yielding two DNA fragments of 170 and 206
      bp. However, no restriction site for Hinfl was found in the PCR products from
      other toxic puffer fishes, including Takifugu niphobles, Takifugu oblongus, and
      Takifugu rubripes. Therefore, the species of the dried dressed fish fillet was
      identified as L. lunaris and its causative agent was identified as tetrodotoxin.

PMID- 11848574
TI  - Occurrence of Salmonella enterica serotype typhimurium DT104A in retail ground
      beef.
AB  - Surveillance data of cattle and human isolates of Salmonella enterica serovar
      Typhimurium DT104 indicate that this pathogen emerged worldwide in the 1980s,
      particularly in cattle. Studies were conducted to determine the prevalence of
      Salmonella Typhimurium DT104 in ground beef. Samples were also tested for the
      presence of generic Escherichia coli. A total of 404 fresh ground beef samples
      obtained at retail stores from New York, San Francisco, Philadelphia, Denver,
      Atlanta, Houston, and Chicago were shipped overnight to Georgia for processing.
      Salmonella spp. were isolated from 14 (3.5%) samples. Eight different serotypes
      were identified among the isolates, including Salmonella Typhimurium (5),
      Salmonella Lille (3), Salmonella Montevideo (1), Salmonella Hadar (1), Salmonella
      Meleagridis (1), Salmonella Cerro (1), Salmonella Kentucky (1), and Salmonella
      Muenster (1). Antibiotic resistance profiles indicated that all five Salmonella
      Typhimurium isolates were resistant to ampicillin, streptomycin,
      sulfamethoxazole, ticarcillin, and tetracycline but that they were sensitive to
      chloramphenicol. Phage typing revealed that all five Salmonella Typhimurium
      isolates were DT104A, a subtype of DT104. All five Salmonella Typhimurium DT104A
      isolates were obtained from ground beef sampled from retail outlets in San
      Francisco. Pulsed-field gel electrophoresis (PFGE) genomic DNA profiles of the
      five Salmonella Typhimurium DT104A isolates from ground beef were
      indistinguishable from those of four control Salmonella Typhimurium DT104 penta
      resistant isolates from cattle that were used for comparison. A total of 102
      generic E. coli isolates were obtained, only three of which were multiresistant
      to antibiotics. In addition, three E. coli isolates were recovered from samples
      that were positive for Salmonella Typhimurium DT104A. No correlation of
      antibiotic resistance profiles was observed between Salmonella Typhimurium DT104A
      and generic E. coli, as two of the three E. coli isolates were susceptible to all
      of the antibiotics tested, and the third isolate was resistant only to
      cephalothin. These data indicate that Salmonella Typhimurium DT104A can be
      isolated from retail ground beef, and because there was little overlap in
      antibiotic resistance patterns between Salmonella Typhimurium DT104A and E. coli
      isolates from the same ground beef samples, these limited data suggest that the
      transfer of antibiotic resistance genes among enteric bacteria in ground beef may
      not be common. This latter observation is further supported by the limited
      isolation of multiantibiotic-resistant E. coli from retail ground beef.

PMID- 11848575
TI  - Synergistic effect of nisin and heat treatment on the growth of Escherichia coli
      O157:H7.
AB  - A combination of nisin and heat treatment was found to inhibit Escherichia coli
      O157:H7 effectively. After organisms were heated at 50, 52.5, and 55 degrees C
      for 5, 10, and 15 min, respectively, nisin was incorporated into the plates of E.
      coli O157:H7 at 0, 25, 50, and 100 IU/ml. The concentration of 100 IU/ml nisin
      significantly inhibited the growth of E. coli O157:H7 heated at 50 and 52.5
      degrees C for 15 min. Nisin treatment at 100 IU/ml for 6 h resulted in the
      elimination of E. coli O157:H7 heated at 55 degrees C for 10 and 15 min.

PMID- 11848576
TI  - Decontaminative effect of frozen acidic electrolyzed water on lettuce.
AB  - We investigated the effects of frozen acidic electrolyzed water (AcEW) on lettuce
      during storage in a styrene-foam container. The lettuce was kept at 2 to 3
      degrees C for 24 h. Populations of aerobic bacteria associated with lettuce
      packed in frozen AcEW were reduced by 1.5 log CFU/g after storage for 24 h. With
      frozen tap water, no microorganism populations tested in this study were reduced.
      A frozen mixture of AcEW and alkaline electrolyzed water (AlEW) also failed to
      reduce populations of microorganisms associated with lettuce. Although chlorine
      gas was produced by frozen AcEW, it was not produced by the AcEW-AlEW mixture.
      This result indicates that the main factor in the decontaminative effect of
      frozen AcEW was the production of chlorine gas. Accordingly, low-temperature
      storage and decontamination could be achieved simultaneously with frozen AcEW
      during distribution.

PMID- 11848577
TI  - The influence of nisin on the thermal resistance of Bacillus cereus.
AB  - Decimal reduction times (D-values) at cooking and autoclaving temperatures (80 to
      120 degrees C) of spores of Bacillus cereus ATCC 1479-8 in rice and milk (13%
      wt/vol) supplemented with nisin (25 microg/ml) were evaluated. The mean D-values
      at 97.8 degrees C in cooked white rice, phosphate buffer (pH 7.0), and rice water
      (pH 6.7) were 3.62, 1,99, and 1.34 min, respectively. From 80 to 100 degrees C,
      the mean reduction in D-values due to the addition of nisin to milk was 40%. The
      D-value at 110 degrees C was approximately 0.86 min for milk (control) and milk
      with nisin. The z-values ranged from 7.32 degrees C (phosphate buffer) to 10.37
      degrees C (milk control).

PMID- 11848579
TI  - Comparison of the compact dry TC and 3M petrifilm ACP dry sheet media methods
      with the spiral plate method for the examination of randomly selected foods for
      obtaining aerobic colony counts.
AB  - Two hundred thirty-six randomly selected food and milk samples were examined to
      obtain aerobic colony counts by two dry sheet media methods and a standard Public
      Health Laboratory Service spiral plate method. Results for 40 samples were
      outside the limits of detection for one or more of the tested methods and were
      not considered. (The limits of detection for the spiral plate method were 200 to
      1 x 10(8) CFU/ml for the spiral plate method and 100 to 3 x 10(6) CFU/ml for the
      dry sheet media methods.) The remaining 196 sets of results were analyzed
      further. When the results from the three methods were compared, correlation
      coefficients were all >0.80 and slopes and intercepts were close to 1.0 and 0.0,
      respectively. Mean log values and standard deviations were very similar for all
      three methods. The results were evaluated according to published UK guidelines
      for ready-to-eat foods sampled at the point of sale, which include a quality
      acceptability assessment that is based on aerobic colony counts. Eighty-six
      percent of the comparable results gave the same verdict with regard to
      acceptability according to the aerobic colony count guidelines. Both dry sheet
      media methods were comparable to the spiral plate method and can be recommended
      for the examination of food.

PMID- 11848578
TI  - The effect of nisin on growth kinetics from activated Bacillus cereus spores in
      cooked rice and in milk.
AB  - The growth kinetics of germinated cells from activated spores of Bacillus cereus
      in cooked white rice and in milk were evaluated at different temperatures for
      control samples and for samples with 25 microg of nisin per ml added. Nisin was
      applied in the form of Nisaplin (10(6) IU/g), which contained 25,000 microg of
      nisin per g. The length of the lag phase for cooked white rice controls was 120 h
      at 10 degrees C, 8 h at 25 degrees C, and 2.5 h at 33 degrees C. The generation
      times for cooked rice were 327.7 min at 10 degrees C, 59.0 min at 25 degrees C,
      and 42.3 min at 33 degrees C; those for milk without nisin were 297.0 min at 20
      degrees C, 31.2 min at 30 degrees C, 28.6 min at 35 degrees C, and 33.7 min at 40
      degrees C; and those for milk with nisin added were 277.2 min at 20 degrees C,
      66.9 min at 30 degrees C, and 66.4 min at 35 degrees C. No development of B.
      cereus was observed for milk with nisin added at 40 degrees C for 12 h, in which
      germinated cells decreased by a decimal reduction time (D) of 4.7 h. A
      temperature of 45 degrees C was shown to be harmful to B. cereus, decreasing the
      germinated cells in both formulations with D-values of 4.3 to 4.6 h. Similar
      inhibition of cell growth at 40 degrees C was not observed with lower nisin
      concentrations.

PMID- 11848580
TI  - Analysis of flour and food samples for cry9C from bioengineered corn.
AB  - StarLink corn is a variety of yellow corn that has been genetically modified by
      the insertion of an altered cry9C gene into the plant genome. resulting in
      expression of the insecticidal Cry9C protein. The U.S. Environmental Protection
      Agency has approved StarLink corn for use in animal feed but not in food intended
      for human consumption. Therefore, under the U.S. Food, Drug, and Cosmetic Act,
      any food intended for human consumption in which the presence of StarLink corn is
      indicated by the presence of either the Cry9C protein or the cry9C gene would be
      considered adulterated. Extraction and PCR-based methods were used to detect the
      presence of the cry9C DNA initially in corn flour and corn meal, and then these
      methods were extended to the analysis of processed corn products, including taco
      shells, cereals, baby foods, party snacks, and chips, for the presence of this
      modified genetic material. In a survey of 63 products, the cry9C transgene was
      detected in 4 taco shells.

PMID- 11848581
TI  - Application of random amplified polymorphic DNA (RAPD) analysis for
      identification of grouper (Epinephelus guaza), wreck fish (Polyprion americanus),
      and Nile perch (Lates niloticus) fillets.
AB  - A random amplified polymorphic DNA (RAPD) method was developed for the specific
      identification of grouper (Epinephelus guaza), wreck fish (Polyprion americanus),
      and Nile perch (Lates niloticus) fillets. Using two different reaction primers
      (S1 and L1), RAPD analysis produced clear fingerprints from which the three fish
      species could be easily identified. This approach is rapid and reliable and
      offers the potential to detect fraudulent or unintentional mislabeling of these
      species in routine seafood authentication analysis.

PMID- 11848582
TI  - A hybrid model of categorization.
AB  - Category learning is often modeled as either an exemplar-based or a rule-based
      process. This paper shows that both strategies can be combined in a cognitive
      architecture that was developed to model other task domains. Variations on the
      exemplar-based random walk (EBRW) model of Nosofsky and Palmeri (1997b) and the
      rule-plus-exception (RULEX) rule-based model of Nosofsky, Palmeri, and McKinley
      (1994) were implemented in the ACT-R cognitive architecture. The architecture
      allows the two strategies to be mixed to produce classification behavior. The
      combined system reproduces latency, learning, and generalization data from three
      category-learning experiments--Nosofsky and Palmeri (1997b), Nosofsky et al., and
      Erickson and Kruschke (1998). It is concluded that EBRW and ACT-R have different
      but equivalent means of incorporating similarity and practice. In addition, ACT-R
      brings a theory of strategy selection that enables the exemplar and the rule
      based strategies to be mixed.

PMID- 11848583
TI  - Directing attention to movement effects enhances learning: a review.
AB  - Studies investigating the influence of the learner's focus of attention, induced
      by instructions or feedback, on motor skill learning are reviewed. In general,
      directing performers' attention to the effects of their movements (external focus
      of attention) appears to be more beneficial than directing their attention to
      their own movements (internal focus of attention). Preliminary evidence is
      presented indicating that an internal attentional focus constrains the motor
      system by interfering with natural control processes, whereas an external focus
      seems to allow automatic control processes to regulate the movements. Support for
      the view that actions are controlled by their anticipated effects comes from
      research demonstrating functional variability in motor control, as well as the
      benefits of purposeful activity in occupational therapy. We explain these results
      in terms of the ideomotor principle of human actions (James, 1890) and its more
      modern derivatives (Hommel, 1996; Prinz, 1990, 1997).

PMID- 11848584
TI  - Can connectionist models of phonology assembly account for phonology?
AB  - Connectionist models have gained considerable success as accounts of how printed
      words are named. Their success challenges the view of grapheme-to-phoneme
      correspondences (GPCs) as rules. By extension, however, this challenge is
      sometimes interpreted also as evidence against linguistic rules and variables.
      This inference tacitly assumes that the generalizations inherent in reading
      (specifically, GPCs) are similar in their scope to linguistic generalizations and
      that they are each reducible to token associations. I examine this assumption by
      comparing the scope of generalizations required for mapping graphemes to phonemes
      and several linguistic phonological generalizations. Marcus (1998b) distinguishes
      between two types of generalizations: those that fall within a model's training
      space and those that exceed it. The scope of generalizations is determined by the
      model's representational choices--specifically, the implementation of operations
      over mental variables. An analysis of GPCs suggests that such generalizations do
      not appeal to variables; hence, they may not exceed the training space. Likewise,
      certain phonological regularities, such as syllable phonotactic constraints and
      place assimilation, may be captured by an associative process. In contrast, other
      phonological processes appeal to variables; hence, such generalizations
      potentially exceed the training space. I discuss one such case, the obligatory
      contour principle. I demonstrate that speakers conform to this constraint and
      that their behavior is inexplicable by the statistical structure of the language.
      This analysis suggests that, unlike GPCs, phonological generalizations may exceed
      the training space. Thus, despite their success in modeling GPCs, eliminative
      connectionist models of phonology assembly may be unable to provide a complete
      account for phonology. To the extent that reading is subject to phonological
      constraints, its modeling may require implementing operations over variables.

PMID- 11848585
TI  - Evidence for a conceptual account of same-different discrimination learning in
      the pigeon.
AB  - We trained pigeons to peck two different buttons in response to 16-icon same
      arrays versus 16-icon different arrays. In the same arrays, the icons were all
      the same as one another, whereas in the different arrays, the icons were all
      different from one another. In Experiment 1, we upset the spatial regularities of
      the displays by disarranging the icons--randomly displacing each icon to reduce
      the degree of perceptual order. The pigeons' discriminative performance was
      unaffected by disarranging. In Experiment 2, spatial regularities were disturbed
      by varying the rotation of the icons within a display. Again, no disruption in
      discriminative performance was observed. These and other findings suggest that
      pigeons treat the 16 icons as either the same or different despite changes in the
      spatial organization or orientation of the icons, thus implicating a conceptual
      rather than a perceptual process in same-different discrimination.

PMID- 11848586
TI  - Episodic-like memory in pigeons.
AB  - It has been proposed that memory for personal experiences (episodic memory,
      rather than semantic memory) relies on the conscious review of past experience
      and thus is unique to humans. In an attempt to demonstrate episodic-like memory
      in animals, we first trained pigeons to respond to the (nonverbal) question "Did
      you just peck or did you just refrain from pecking?" by training them on a
      symbolic matching task with differential responding required to the two line
      orientation samples and reinforcing the choice of a red comparison if they had
      pecked and the choice of a green comparison if they had not pecked. Then, in
      Experiment 1, after providing the conditions for (but not requiring) the pigeons
      to peck at one new stimulus (a yellow hue) but not at another (a blue hue), we
      tested them with the new hue stimuli and the red and green comparisons. In
      Experiment 2, we tested the pigeons with novel stimuli (a circle, which they
      spontaneously pecked, and a dark response key, which they did not peck) and the
      red and green comparisons. In both experiments, pigeons chose the comparison
      appropriate to the response made to the test stimulus. Thus, the pigeons
      demonstrated that they could remember specific details about their past
      experiences, a result consistent with the notion that they have the capacity for
      forming episodic-like memories.

PMID- 11848587
TI  - Conditions favoring retroactive interference between antecedent events (cue
      competition) and between subsequent events (outcome competition).
AB  - Retrieval of a target association (A-B) is often impaired if training of a
      similar association is interpolated between target training and testing; this is
      known as retroactive interference. Two experiments, in which rats were used as
      subjects in a sensory preconditioning preparation, studied the associative nature
      of retroactive interference between antecedent events (i.e., A and C in the A-B,
      C-B paradigm) and between subsequent events (i.e., B and C in the A-B, A-C
      paradigm). With the present preparation, retroactive interference was equally
      strong between antecedent events and between subsequent events. Moreover,
      interference occurred only if (1) an association was trained in the interpolated
      phase and (2) the target and interpolated associations had a common element in a
      common temporal location.

PMID- 11848588
TI  - Variability signatures distinguish verbal from nonverbal counting for both large
      and small numbers.
AB  - Humans appear to share with animals a nonverbal counting process. In a nonverbal
      counting condition, subjects pressed a key a numeral-specified number of times,
      while saying "the" at every press. The mean number of presses increased as a
      power function of the target number, with a constant coefficient of variation
      (c.v.), both within and beyond the proposed subitizing range (1-4 or 5),
      suggesting small numbers are represented on the same continuum as larger numbers
      and subject to the same noise process (scalar variability). By contrast, when
      subjects counted their presses out loud as fast as they could, the c.v. decreased
      as the inverse square root of the target value (binomial variability instead of
      scalar variability). The unexpected power-law relation between target value and
      mean number of presses in nonverbal counting suggests a new hypothesis about the
      development of the function relating number symbols to mental magnitudes.

PMID- 11848589
TI  - Perceptual learning with odors: implications for psychological accounts of odor
      quality perception.
AB  - After two odors have been experienced in a mixture, the pair are subsequently
      rated as sharing more qualities and smelling more alike than equally exposed
      controls. These effects may result from the retrieval of a common mixture memory
      when either component is sniffed alone. If correct, odor pairs experienced
      together in a mixture should also be less discriminable than those experienced an
      equal number of times but in different mixtures. This was tested here by exposing
      participants to two odor mixtures (either AX, BY or AY, BX) and then testing
      their ability to discriminate between the components. As predicted, odors
      previously experienced together as a mixture were less discriminable than
      controls. These and related findings noted above suggest that learning and memory
      play an important role in odor quality perception.

PMID- 11848590
TI  - Time course of amodal completion revealed by a shape discrimination task.
AB  - We measured the extent of amodal completion as a function of stimulus duration
      over the range of 15-210 msec, for both moving and stationary stimuli. Completion
      was assessed using a performance-based measure; a shape discrimination task that
      is easy if the stimulus is amodally completed and difficult if it is not.
      Specifically, participants judged whether an upright rectangle was longer
      horizontally or vertically, when the rectangle was unoccluded, occluded at its
      corners by four negative-contrast squares, or occluded at its corners by four
      zero-contrast squares. In the zero-contrast condition, amodal completion did not
      occur because there were no occlusion cues; in the unoccluded condition, the
      entire figure was present. Thus, comparing performance in the negative-contrast
      condition to these two extremes provided a quantitative measure of amodal
      completion. This measure revealed a rapid but measurable time course for amodal
      completion. Moving and stationary stimuli took the same amount of time to be
      completed (approximately 75 msec), but moving stimuli had slightly stronger
      completion at long durations.

PMID- 11848592
TI  - Making features similar: comparison processes affect perception.
AB  - In this paper, the constructive nature of comparison processes (both similarity-
      and difference-oriented judgments) is examined through their effects on visual
      perception. Previous research has shown that comparison processes enhance the
      tendency to interpret ambiguous objects in the light of the unambiguous objects
      with which they are compared (Medin, Goldstone, & Gentner, 1993). In the present
      paper, it is argued that comparison processes affect not only the interpretation
      of objects, but also their perception. In addition, it is argued that the
      perceptual effects of similarity-oriented comparison processes differ from those
      of difference-oriented comparison processes. Accordingly, it is demonstrated that
      when estimation of an object's size is preceded by similarity-oriented
      comparisons, the Ebbinghaus illusion practically disappears, whereas prior
      difference-oriented comparisons tend to enhance the illusion.

PMID- 11848591
TI  - The effects of occlusion and past experience on the allocation of object-based
      attention.
AB  - There is considerable evidence indicating that cuing a specific portion of an
      object results in the entire object's being attended to. In the present study, we
      examined whether previous experience with an object could halt perceptual (i.e.,
      amodal) completion. In Experiment 1, two parallel rectangles were initially
      displayed, and then the middle portions of these objects were occluded.
      Attentional cuing effects were found for both discrete portions of the completed
      rectangles. In the final two experiments, four discrete objects were initially
      displayed, followed by the same occluder as that used in the first experiment.
      The appearance of the occluder (500 msec before the cue in Experiment 2,100 msec
      before the cue in Experiment 3) allowed the four discrete objects to be completed
      into two rectangles. Attentional cuing effects were found for the completed
      rectangles in both experiments, indicating that previous experience was not
      sufficient to halt the amodal completion of objects.

PMID- 11848593
TI  - The role of meaning and familiarity in mental transformations.
AB  - Eighty-four participants mentally rotated meaningful and meaningless objects.
      Within each type of object, half were simple and half were complex; the
      complexity was the same across the meaningful and meaningless objects. The
      patterns of errors were examined as a function of the type of stimuli (meaningful
      vs. meaningless), complexity, and angle of rotation. The data for the meaningful
      objects showed steeper slopes of rotation for complex objects than that for
      simple objects. In contrast, the simple and complex meaningless objects showed
      comparable increases in error rates as a function of angle of rotation.
      Furthermore, the slopes remained comparable after pretraining that increased
      familiarity with the objects. The results are discussed in terms of underlying
      representations of meaningful and meaningless objects and their implications to
      mental transformations. The data are consistent with a piecemeal rotation of the
      meaningful stimuli and a holistic rotation of the meaningless stimuli.

PMID- 11848594
TI  - Visual search: efficiency continuum or distinct processes?
AB  - Whether visual search involves two distinct processes--traditionally referred to
      as serial and parallel--or a single process operating on a continuum of
      efficiency or speed, is an issue with a long history in the study of attention.
      On the basis of the unimodality of search slope distributions in a very large
      data set, Wolfe (1998) argued for a continuum model. Reanalysis of this data set
      using statistical procedures more appropriate for adjudicating between continuous
      and discontinuous models supports the existence of two distinct processes.

PMID- 11848595
TI  - Spontaneous allocation of visual attention: dominant role of uniqueness.
AB  - Common sense suggests that unique or abruptly changing (transient) elements in a
      visual scene often draw attention involuntarily. Visual search studies paint a
      seemingly different picture, however Unique items usually draw attention
      involuntarily only when observers seek a unique target. One type of transient-
      abrupt onsets--draws attention involuntarily, but only when the observer is
      seeking an onset (Folk, Remington, & Johnston, 1992). One way of reconciling
      common-sense with these findings is to suppose that when people view a scene with
      no specific goal or task, they adopt a default set, which might prioritize
      novelty and/or transients. In two experiments, 336 subjects saw a single display
      of six items for 900 msec, expecting to have to describe it (Experiment 1) or
      make an aesthetic judgment about it (Experiment 2). One item in the display was
      either uniquely flashing (surrounded by static items) or uniquely static
      (surrounded by flashing items). In both studies, the unique item, even if static,
      was more often reported than the non-unique item, with flashing items enjoying an
      additional advantage.

PMID- 11848596
TI  - Types and tokens in transsaccadic object identification: effects of spatial
      position and left-right orientation.
AB  - What types of representations support our ability to integrate information
      acquired during one eye fixation with information acquired during the next
      fixation? In Experiment 1, transsaccadic integration was explored by manipulating
      whether or not the relative position of a picture of an object was maintained
      across a saccade. In Experiment 2, the degree to which visual details of a
      picture are coded in a position-specific representational system was explored by
      manipulating whether or not both the relative position and the left-right
      orientation of the picture were maintained across a saccade. Position-specific
      and nonspecific preview benefits were observed in both experiments. Only the
      position-specific benefits were influenced by the number of task-relevant
      pictures presented in the preview display (Experiment 1) and the left-right
      orientation of the picture presented in the preview display (Experiment 2). The
      results support a model of transsaccadic integration based on two independent
      representational systems. One system codes abstract, prestored object types, and
      the other codes episodic tokens consisting of stimulus properties linked to scene
      or configuration-based position markers.

PMID- 11848598
TI  - Infants attend to second-order relational properties of faces.
AB  - Two experiments investigated whether 7-month-old infants attend to the spatial
      distance measurements relating internal features of the human face. A visual
      preference paradigm was used, in which two versions of the same female face (one
      either lengthened or shortened, and one nonmodified) were presented
      simultaneously. In Experiment 1, infants looked longer at the nonmodified faces,
      which were determined to match the average distance relationships found in a
      sample of faces drawn from the same population. Longer looking times for modified
      faces were found in Experiment 2, in which the nonmodified faces were unusually
      long and the modified faces conformed to average distance measurements. It is
      proposed that infants' attention to the spatial relations of internal face
      features is an optimal tool for lifelong face recognition.

PMID- 11848597
TI  - To see and remember: visually specific information is retained in memory from
      previously attended objects in natural scenes.
AB  - What is the nature of the representation formed during the viewing of natural
      scenes? We tested two competing hypotheses regarding the accumulation of visual
      information during scene viewing. The first holds that coherent visual
      representations disintegrate as soon as attention is withdrawn from an object and
      thus that the visual representation of a scene is exceedingly impoverished. The
      second holds that visual representations do not necessarily decay upon the
      withdrawal of attention, but instead can be accumulated in memory from previously
      attended regions. Target objects in line drawings of natural scenes were changed
      during a saccadic eye movement away from those objects. Three findings support
      the second hypothesis. First, changes to the visual form of target objects (token
      substitution) were successfully detected, as indicated by both explicit and
      implicit measures, even though the target object was not attended when the change
      occurred. Second, these detections were often delayed until well after the
      change. Third, changes to semantically inconsistent target objects were detected
      better than changes to semantically consistent objects.

PMID- 11848599
TI  - Semantic processing in visual word recognition: activation blocking and domain
      specificity.
AB  - Lexical decision to a target is typically facilitated when a related prime is
      simply read, but is typically eliminated if subjects carry out a letter search on
      the prime when probe and prime appear simultaneously. Three experiments involving
      the addition of a task-irrelevant word to this prime search paradigm address (1)
      Stolz and Besner's (1996, 1998) account in which semantic priming is eliminated
      because letter search on the prime instantiates an activation block between
      lexical and semantic levels of representation, (2) Chiappe, Smith, and Besner's
      (1996) account that activation blocking is domain specific, and (3) Neely and
      Kahan's (2001) claim that semantic activation is context independent and capacity
      free. The results are (1) consistent with the account that activation blocking is
      general to a level, rather than item specific, (2) consistent with the account
      that activation blocking is domain specific, and (3) inconsistent with the claim
      that semantic activation is context independent and capacity free.

PMID- 11848600
TI  - Loss of rapid phonological recoding in reading Hanja, the logographic script of
      Korean.
AB  - The role that recent experience has in the processing of Korean Hanja characters
      was investigated in two masked priming experiments. Two groups of Korean native
      speakers that differed in their recent exposure to Hanja were asked to name
      single Hanja characters (targets) that were immediately preceded by masked
      presentations of the same characters (repetition priming), Hanja characters that
      were homophones of the target (homophone priming), or unrelated characters
      (baseline). The results showed that the group that had been less recently exposed
      made more errors and were slower than the group that had been the more recently
      exposed. Furthermore, there was no character homophone priming for the less
      recently exposed group, although they did show a robust repetition priming
      effect. On the other hand, the more recently exposed group showed both strong
      character repetition and homophone priming effects. We suggest that regular
      exposure to characters supports their rapid and automatic processing. It is
      argued that the different patterns of priming for the two groups were due to how
      rapidly the orthographic and phonological information of the prime could be
      resolved.

PMID- 11848602
TI  - When it does hurt to try: adult age differences in the effects of instructions on
      implicit pattern learning.
AB  - Trying to learn sometimes impairs implicit learning of artificial grammars and of
      control systems. We asked whether such negative effects of trying also occur in
      implicit learning of subtle sequential regularities and whether such effects vary
      with adult age. Young (n = 12, age = 20-23) and older (n = 24, age = 60-80)
      adults completed an alternating serial response time task in which predictable
      pattern events alternated with random ones in a visual/spatial display. Half of
      the participants were informed about the pattern and were instructed to try to
      discover it (intentional instructions), and half were not (incidental
      instructions). Age-related deficits in implicit learning occurred for both
      conditions. In addition, for the older group, but not for the younger one,
      intentional instructions impaired implicit pattern learning. This negative effect
      of trying to learn demonstrates another similarity among implicit learning tasks,
      supporting the view that some common processes underlie different forms of
      implicit learning.

PMID- 11848601
TI  - Bias in conceptual priming.
AB  - In recent years, Ratcliff, McKoon, and colleagues have argued that priming in
      perceptual implicit memory tests is the result of biases in information
      processing. Three experiments are presented that extend this framework to the
      conceptual implicit memory domain. Participants studied a list of words before
      receiving a set of general knowledge questions. For some questions, participants
      studied the correct answer; for others, they studied a similar but incorrect
      answer. Although study of a correct answer facilitated performance, study of the
      similar alternative hurt performance. Costs and benefits of previous study were
      observed in both production and forced-choice tasks. However, there was no
      benefit of previous study when participants studied both the correct answer and
      the similar but incorrect alternative. The pattern of results indicates that
      participants were biased to respond with previously studied words on the
      conceptual implicit memory test. This pattern is concordant with the biased
      information-processing approach to priming.

PMID- 11848603
TI  - In what sense is implicit memory "episodic"? The effect of reinstating
      environmental context.
AB  - We consider three aspects of the term episodic. Previous literature shows
      implicit memory does not make conscious autobiographical reference but does code
      an item's intrinsic context (e.g., perceptual detail). Here, we consider
      extrinsic context--namely, that not directly processed as part of item
      identification and not overtly relevant to the task. Study-test mismatch in
      environmental context (outdoors vs. indoors) reduced memory in an explicit stem
      cued recall task but had no effect on repetition priming in an implicit stem
      completion task. This was true even for very low frequency words. We support the
      view that implicit memory reflects traces within perceptual (or semantic)
      knowledge-based systems that are instance specific but do not code the full
      spatiotemporal context information necessary to support conscious recollection.
      We also interpret our results as consistent with differences in environmental
      context specificity between free recall and recognition.

PMID- 11848604
TI  - Data-driven recognition memory: a new technique and some data on age differences.
AB  - In this study, we investigate the effect on recognition memory of having target
      and distractor stimuli consisting of different combinations of low-level elements
      (letters), relative to when targets and distractors consist of combinations of
      the same elements (nonoverlap and overlap conditions, respectively). It was found
      that recognition memory was enhanced in the nonoverlap condition, even though
      subjects reported being unaware of this experimental manipulation. This confirms
      the importance of perceptually driven processing in the implicit memory component
      of recognition memory. The extent to which this effect occurs is found to be age
      dependent, with elderly subjects benefiting more from having targets and
      distractors consisting of nonoverlapping elements. This is consistent with the
      notion that elderly subjects show less reliance on item-specific/contextual
      detail to support recognition memory.

PMID- 11848605
TI  - Expecting dirt but saying dart: the creation of a blend memory.
AB  - During a naming task, time pressure and a manipulation of the proportion of
      related prime-target pairs were used to induce subjects to generate an
      expectation to the prime. On some trials, the presented target was
      orthographically and generally phonologically similar to the expected target. The
      expectancy manipulation was barely detectable in the priming data but was clearly
      evident on a final recognition test. In addition, the recognition data showed
      that the nearly simultaneous activation of an expectation and sensory information
      derived from the orthographically and phonologically similar target produced a
      false memory. It is argued that this represents a blend memory.

PMID- 11848607
TI  - Causes of taxonomic sorting by adults: a test of the thematic-to-taxonomic shift.
AB  - The tendency among adults to sort items into taxonomic and thematic categories
      was examined in two experiments. Past demonstrations of adults' preference for
      taxonomic categories have usually not used stimuli with a salient thematic
      organization. The stimuli in Experiment 1 could be divided into three equal-size
      categories either thematically or taxonomically. Under two sets of instructions,
      the majority of the college-student subjects sorted thematically. In Experiment
      2, a subset of the stimuli was changed so that those within it were strongly
      taxonomically organized. Subjects then preferred to sort the remaining items
      taxonomically as well. The two experiments explain why many past sorting studies
      have yielded a taxonomic preference in adults and provide further evidence
      against a global change from thematic to taxonomic preference with development.

PMID- 11848606
TI  - Retrieval conditions and false recognition: testing the distinctiveness
      heuristic.
AB  - High levels of false recognition are observed after people study lists of
      semantic associates that all converge on a nonpresented lure word. In previous
      experiments, we have found that orienting participants to encode distinctive
      information about study list items by presenting them as pictures as opposed to
      words produces marked reductions in false recognition. We have suggested that
      these reductions reflect the operation of a distinctiveness heuristic:
      Participants demand access to detailed pictorial information in order to support
      a positive recognition decision. The present experiments provide additional
      evidence on this point and allow us to distinguish between the distinctiveness
      heuristic account and an alternative account based on the impoverished encoding
      of relational information that occurs when one is studying pictures. In
      Experiment 1, even when only half of the items in a study list were presented as
      pictures, a general suppression of false recognition was observed that could be
      attributable to impoverished encoding of relational information. Experiment 2
      provided a critical test of the distinctiveness heuristic account: We manipulated
      test instructions and found that differences in false recognition rates between
      picture and word encoding were attenuated in a retrieval condition that did not
      encourage reliance on a distinctiveness heuristic.

PMID- 11848608
TI  - What is minimal about predictive inferences?
AB  - Pronunciation of a probe word that relates to a highly predictable event is
      typically facilitated when the probe immediately follows the target sentence, but
      not when it is delayed until after a second sentence. These findings suggest that
      inferences about highly predictable events are minimally drawn during reading.
      Using a similar paradigm, in which the probe was delayed, we found significant
      priming in a reading condition that encouraged focus on the referential state of
      affairs (situation level) expressed in the sentences. In contrast, significant
      priming for predictive texts was not observed in a reading condition that
      encouraged focus on the text per se (text level). These results are interpreted
      within a theoretical model that assumes that predictive inferences are
      represented at a situational level only, whereas explicitly presented information
      is represented at several levels (text and situational). It is in this sense that
      predictive inferences may be said to be minimally represented.

PMID- 11848609
TI  - Interpretation of significance levels by psychological researchers: the .05 cliff
      effect may be overstated.
AB  - Comments about previous studies indicate that the interpretation of significance
      levels by psychological researchers is unequivocally dictated by a binary
      decision-making framework. In particular, confidence in a p level would drop
      abruptly just beyond the fateful .05 level (cliff effect). A replication of
      Rosenthal and Gaito's (1963) experiment on the degree of confidence in p levels
      shows that these claims should be moderated. Detailed analysis of individual
      curves reveals that the attitude of researchers toward p values is far from being
      as homogeneous as might be expected. However, most psychological researchers in
      our study rated graduated confidence judgments, as either exponential or linear.
      Only a minority of all-or-none respondents exhibited an abrupt drop in
      confidence.

PMID- 11848610
TI  - Lexical guidance in sentence processing: a note on Adams, Clifton, and Mitchell
      (1998).
AB  - Mitchell (1987) conducted a self-paced reading experiment that showed that people
      experienced difficulty reading a noun phrase when it immediately followed an
      intransitive verb. From this, he argued for a two-stage theory of parsing, in
      which verb subcategorization information is initially ignored. In response,
      Adams, Clifton, and Mitchell (1998) found no evidence to support this claim in an
      eye-tracking experiment and argued that Mitchell's segmentation procedure
      distorted the parsing process. We report an eye-tracking experiment, in which
      materials similar to those in Adams et al., but with longer noun phrases, were
      used, that showed a pattern of difficulty similar to Mitchell's findings. Hence,
      Mitchell's results did not depend on the use of an artificial method of
      presentation. The results cast further doubt on the adequacy of constraint-based
      accounts of parsing.

PMID- 11848611
TI  - The Stroop effect and single letter coloring: what replicates and what doesn't?

PMID- 11848612
TI  - HER-2/neu-Positive breast carcinoma: molecular concomitants by proteomic analysis
      and their therapeutic implications.
AB  - OBJECTIVE: To identify molecular events that occur concomitantly in HER-2/neu
      protein-receptor-positive breast carcinoma and to identify pathogenetic and
      growth-modulating sequences around its tyrosine-kinase-mediated cell
      proliferation and tumorigenesis that may be amenable to therapeutic
      interventions. METHODS: Slides containing sections of 3 pelleted human breast
      carcinoma cell lines (DAKO HercepTest) and expressing HER-2/neu protein-receptor
      scored at 3+ (SKBR-3), 1+ (MDA-175), and 0 (MDA-231), respectively, were reacted
      in immunohistochemical procedures for the detection of the following antigens:
      HER-2, estrogen receptor (ER), progesterone receptor (PR), Ki-67, cyclin D1, c
      Jun, epidermal growth factor receptor (EGFR), transforming growth factor (TGF)
      alpha, components of the JAK/STAT signal transduction pathway (gp130, interleukin
      [IL]-6, and IL-11), p21ras, farnesyl transferase (FT), and potential growth
      inhibitory/proapoptotic and antiapoptotic-related proteins (latency-associated
      peptide [LAP] of TGF-beta1, TGF-beta receptor [R] II, p53, and bcl-2 and
      cyclooxygenase [COX]-2). Immunoreactivities were graded using bright-field
      microscopy on a scale of 0 to 3+. RESULTS: Commonalities noted among the 3 cell
      lines include absent (0) chromogenic signals for ER and PR, relatively high Ki-67
      proliferation indices (54, 40, and 61%, respectively), and positive signals (1 to
      3+) for IL-6, IL-11, TGF-alpha, EGFR, TGF-beta1 (LAP), TGF-betaRII,FT, p21ras,
      and p53. Strong intranuclear immunopositivities for cyclin D1 and c-Jun antigens
      were evident in the MDA-231 cell line but absent or rare (0 to +/-) in SKBR-3.
      Conversely, gp130 antigen was readily detected in the SKBR-3 cell line but only
      weakly expressed (+/-) in MDA-231, whereas bcl-2 and COX-2 were expressed in the
      latter and not in SKBR-3 cells. CONCLUSIONS: These data suggest that signal
      transduction through farnesylated p21 ras is part of the pathogenesis of tyrosine
      kinase-mediated proliferation in HER-2/neu protein-receptor-positive breast
      carcinoma. Collaborations with the EGFR and JAK/STAT systems in these molecular
      events are also likely. Potential therapeutic agents include downregulators of c
      erb-B1 (EGFR) and -B2 (HER-2) receptor expressions, inhibitors of tyrosine kinase
      and farnesylation, and activators of growth inhibitory/proapoptotic pathways.

PMID- 11848613
TI  - Diagnostic approach to prostate cancer using total prostate specific antigen
      based parameters together.
AB  - This prospective study investigated the value of serum total prostate specific
      antigen (tPSA)-based parameters in the diagnosis of prostate cancer (PCa). Serum
      tPSA, free to tPSA ratio (f/tPSA), PSA density (PSAD), and PSA transition zone
      (PSAT) were evaluated in 110 patients with histologically confirmed benign
      prostate hyperplasia (BPH) and 98 patients with PCa. Once the serum tPSA was
      elevated (greater than 4 ng/ml) or digital rectal examination (DRE) was
      suspicious, transrectal ultrasound-guided biopsies were recommended. The tPSA,
      f/tPSA, PSAD, and PSAT levels were significantly different between the BPH and
      PCa groups. In patients with a tPSA level of 4.1-9.9 ng/ml or an abnormal DRE
      finding, only PSAT was found to have discriminating power. The cut-off values
      were 0.15 for f/tPSA, 0.30 for PSAT, and 0.15 for PSAD. The diagnostic
      sensitivity of a positive result for one of these parameters in the whole group
      was 84%, but 75% in patients with a tPSA of 4.1-9.9 ng/ml or an abnormal DRE
      finding. The diagnostic specificity of positive results for 3 parameters was 92%
      in the whole group and 93% in patients with a tPSA of 4.1-9.9 ng/ml or an
      abnormal DRE finding. All parameters were influenced by the histological grades.
      Histological grades showed a negative correlation (r = -0.56) with f/t PSA and a
      positive correlation (r = 0.44) with PSAT. No diagnostic marker investigated
      heretofore was able to rule out or detect early PCa in patients with a PSA level
      of 4.1-9.9 ng/ml. Using the PSA-based parameters together can be helpful in
      management of these patients. If all of the PSA-based parameters are negative,
      biopsy might be postponed; patients who have three positive PSA-based parameters
      should be biopsied. In case of one or two of the parameters, the patient's age
      and race should be considered in clinical decision-making.

PMID- 11848614
TI  - A testing algorithm for determination of HER2 status in patients with breast
      cancer.
AB  - The HER2 gene is amplified and overexpressed in 25-30% of breast carcinomas.
      Assessment of HER2 status for prognosis and treatment of breast cancer patients
      can be performed by immunohistochemistry and/or fluorescence in situ
      hybridization (FISH). To develop a testing algorithm for HER2 in breast cancers,
      we used FISH analysis to determine the HER2 gene copy number and immunostaining
      to detect the p185 protein. Interlaboratory, interobserver, and intermethod
      variabilities of immunohistochemistry were assessed. In 24 invasive breast
      carcinomas, the indices of HER2 status obtained by FISH and by a reference
      laboratory's DAKO HercepTest (immunostain) gave an overall concordance of 96%.
      The reference laboratory's stained slides were re-interpreted by an in-house
      panel of pathologists; the interpretation differed in one case. The panel's
      interpretations were concordant with the FISH results in all 24 cases.
      Interobserver variability for the panel's immunohistochemistry interpretations
      was assessed using three different immunostaining methods on 70 slides. The
      numerical (0-1+, 2+, 3+) scores showed greater variability among observers than
      did the overall positive/negative results. One pathologist reported inconsistent
      results in >30% of the slides evaluated. Borderline scoring of 1-2+ was reported
      in 18 slides (23%) by at least one observer. Incongruent interobserver
      immunohistochemistry scores, leading to different positive and negative
      interpretations, were obtained with 5 slides (7%). The majority of consensus
      positive cases exhibited strong membrane staining (3+). The majority of consensus
      negative cases scored as 0. Based on these observations, we developed a testing
      algorithm that maximizes the benefits of FISH and immunohistochemistry, providing
      physicians with accurate results for appropriate clinical care.

PMID- 11848615
TI  - Changes of PSA concentrations in serum and saliva of healthy women during the
      menstrual cycle.
AB  - This study investigated the changes of prostate specific antigen (PSA)
      concentrations in serum and saliva of women during the menstrual cycle. Thirty
      healthy volunteers (age 23-35 yr) were enrolled in the study. During the
      menstrual cycle, serum and saliva PSA concentrations on days 9 (follicular phase)
      and 14 (mid-cycle) were significantly higher than on days 4 (early follicular
      phase) and 21 (luteal phase). The expected changes in gonadal hormones were seen,
      as evidenced by significantly higher serum estradiol and progesterone
      concentrations during the midcycle and luteal phase, compared to the other phases
      of the cycle. Serum PSA concentrations were positively correlated with salivary
      PSA concentrations at all 4 times (days 4, 9, 14, and 21) of the menstrual cycle,
      but not with the serum progesterone or estrogen concentrations. This study
      suggests that salivary PSA, rather than being produced in the salivary gland, may
      reflect the serum PSA during the normal menstrual cycle.

PMID- 11848616
TI  - Rapid, sensitive diagnosis of hemolytic anemia using antihemoglobin antibody in
      hypotonic solution.
AB  - We have developed a new and simple flow cytometric method to detect damaged red
      blood cells (RBCs) using anti-Hb in hypotonic solution. We studied a total of 200
      patients, including 62 patients with schistocytosis, 8 postsplenectomy patients,
      and 108 healthy controls. Peripheral blood (2 microl) was stained with
      phycoerythrin-conjugated (PE) antihemoglobin antibody (anti-Hb) in 0.6% (w/v)
      NaCl solution, and analyzed by flow cytometry omitting the washing step. The
      proportion of RBCs stained by anti-Hb was 0.55% (SD +/-0.23%) in normal controls
      and was significantly higher in patients with schistocytosis (2.95+/-2.95%, p
      <0.001). Six of 108 blood samples from normal controls and 60 of 62 samples from
      schistocytosis patients showed > or =1.01% stained RBCs (ie, values > mean+2SD of
      normal controls). The number of schistocytes counted by microscopic examination
      correlated with the proportion of RBCs stained by anti-Hb (r = 0.637, p <0.001).
      The proportions of stained RBCs in blood samples with malaria, spherocytosis, and
      elliptocytosis were also significantly higher than in normal controls. However,
      the results in postsplenectomy and iron-deficiency anemia (IDA) patients were not
      significantly different from the normal controls; the number of schistocytes in
      postsplenectomy patients was not related to the proportion of RBCs stained by
      anti-Hb. Based on these findings, flow cytometry of damaged RBCs using anti-Hb in
      hypotonic solution is a simple, sensitive, and accurate method to detect active
      hemolysis.

PMID- 11848617
TI  - Differences of creatine kinase MB and cardiac troponin I concentrations in normal
      and diseased human myocardium.
AB  - The diagnosis of myocardial infarction (MI) is established in patients with chest
      pain and equivocal electrocardiogram changes by demonstrating a rise in blood
      levels of creatine kinase MB (CK-MB) and/or an increase in cardiac troponin I
      (cTnI) or cardiac troponin T (cTnT). Previous studies have shown that levels of
      CK-MB are increased in the left ventricle of individuals with heart disease;
      however, it has not been established whether there are differences in the
      ventricular myocardium concentrations of cTnI in diseased compared to healthy
      hearts. Using a simple extraction technique, concentrations of CK-MB and cTnI
      were measured in the left ventricle (LV) of six hearts obtained at autopsy from
      individuals ranging in age from 25 to 79 yr, with and without evidence of cardiac
      disease. The results show an 86-fold higher concentration of CK-MB and 7.7-fold
      lower concentration of cTnI in left ventricular myocardium of older men with and
      without cardiac disease, compared to that of younger men (< age 35 yr) without
      heart disease. These data suggest that age may need to be considered when setting
      cutoff limits for these markers for the diagnosis of myocardial infarction.

PMID- 11848618
TI  - HDL cholesterol levels in patients with molecularly defined familial
      hypercholesterolemia.
AB  - Familial hypercholesterolemia (FH) is the most common genetic disorder leading to
      premature atherosclerosis. Typically, it is due to mutations in the LDL receptor
      gene resulting in elevated total and LDL cholesterol levels. The type of the LDL
      receptor gene mutations may affect the severity of hypercholesterolemia and
      consequently the incidence of coronary atherosclerosis. Furthermore, high-density
      lipoprotein (HDL) cholesterol levels have been recently shown to be an
      independent risk factor for coronary heart disease in this population. We
      examined the effect of the type of the LDL receptor gene mutations and of common
      gene polymorphisms possibly affecting HDL metabolism [cholesterol ester transfer
      protein (CETP), apolipoprotein A-IV (ApoA-IV), angiotensin converting enzyme
      (ACE), and apolipoprotein E (ApoE)] on HDL cholesterol levels in patients with
      molecularly defined heterozygous FH who were attending our lipid clinic (n=84).
      The nature of the LDL receptor gene mutation (81T>G, n=12; 858C>A, n=13; 1285G>A,
      n=12; 1646G>A, n=22; and 1775G>A, n=25) did not significantly influence HDL
      cholesterol levels. Unlike other gene polymorphisms, the apolipoprotein (apo) E
      gene polymorphism did significantly affect these levels. In fact, the presence of
      the E4 allele was associated with lower HDL cholesterol levels compared to
      patients not carrying this allele. We conclude that HDL cholesterol levels in
      heterozygous FH patients may be affected by the apoE gene polymorphism.

PMID- 11848619
TI  - Quantitative analysis of urine sediment using newly designed centrifuge tubes.
AB  - We quantified the formed elements of urine sediment using newly designed plastic
      centrifuge tubes with top and bottom openings and a 0.5 ml sized bottom ball (YZ
      tube). This design minimizes the adherence of formed elements that occurs on the
      glass surface of conventional tubes. The numbers of white blood cells (WBC) and
      red blood cells (RBC) using glass tubes did not differ from those observed using
      YZ tubes. However, the YZ tube method detected renal casts more frequently than
      the conventional glass tube method; the detection rate for renal casts in normal
      urine samples was 21.4% vs 2.9%, in samples from hospitalized patients it was
      47.5% vs 10.2%, and from patients with kidney disease it was 88.9% vs. 44.4%.
      Especially, the YZ tube method detected more hyaline casts in all types of
      samples. The correlation between the glass tube and YZ tube methods was good for
      WBC (r=0.996), RBC (r=0.964), and epithelial cell count (r=0.939), but the
      correlation was weak for casts (r=0.511 for hyaline casts; r=0.359 for other
      casts). In conclusion, the YZ tube method of urine sediment analyses is an easy
      and accurate quantitative method; it is recommended as the method of choice for
      detecting and quantifying pathological casts in urine. (received

PMID- 11848620
TI  - Comparison of M4 and M4RT media for transporting cervical swab samples for PCR
      detection of Chlamydia trachomatis and Neisseria gonorrhoeae.
AB  - In a prospective study, M4RT medium was compared to the traditional M4 medium to
      transport cervical swab specimens for Neisseria gonorrhoeae/Chlamydia trachomatis
      (NG/CT) PCR testing using the Roche COBAS Amplicor. Two cervical swab samples
      were collected from 270 consecutive patients screened for NG/CT in a satellite
      facility. The swabs were placed individually in M4RT and M4 medium and were
      immediately refrigerated, transported to the laboratory on wet ice, and stored at
      2 to 8 degrees C until the PCR testing was performed within 7 da of collection.
      Seven of the cervical swab samples transported in M4 or M4RT were PCR positive
      for CT. Two additional samples transported in M4RT and a third swab transported
      in M4 were CT PCR positive. These samples were PCR negative in the alternative
      medium. Similarly, 12 of the cervical swabs transported in M4 or M4RT were NG PCR
      positive. Three additional swabs transported in M4 media were NG PCR positive.
      Initially, 2 of these samples when transported in M4RT were NG PCR equivocal and
      were considered NG PCR positive on repeat testing. Similarly, 2 additional swab
      samples transported in M4 RT media were NG PCR positive. These samples, when
      transported in M4 media, were NG PCR equivocal or negative. However, on repeat
      testing the equivocal sample was considered NG PCR positive. We conclude M4 and
      M4RT transport media are equally reliable for transporting cervical swab samples
      for NG/CT PCR testing. M4RT medium is more convenient to use, as it did not
      require refrigeration until it was inoculated with the clinical sample.

PMID- 11848621
TI  - Isoform-specific effect of apolipoprotein E on endocytosis of beta-amyloid in
      cultures of neuroblastoma cells.
AB  - Investigation of the interactions of nerve cells with human apolipoprotein E
      (apoE), beta-amyloid (Abeta), and their complex, which are known to be included
      in senile plaques, is necessary to clarify the functional role of apoE in the
      pathogenesis of Alzheimer's disease. Using flow cytometric analysis, we
      investigated the isoform-specific effects of apoE on the endocytosis of Abeta in
      cultured neuroblastoma cells. The level of internalized Abeta within the cells
      was dependent on the culture time and the kind of apoE isoform present. Both
      apoE3 and apoE4 enhanced the internalization of Abeta; however, no difference was
      observed between their effects. The internalized Abeta was hardly catabolized at
      all in the presence of apoE4, while rapid clearance of Abeta was observed in the
      presence of apoE3. Unlike apoE3 and apoE4, apoE2 had no effect on Abeta clearance
      from the media. The isoform-specific effects of apoE on the endocytosis of Abeta
      may be implicated in the development of Alzheimer's disease, and if so, each
      isoform of apoE would induce a different incidence of that disease.

PMID- 11848622
TI  - Aluminum-induced dendritic pathology revisited: cytochemical and electron
      microscopic studies of rabbit cortical pyramidal neurons.
AB  - Intracisternal administration of aluminum maltolate induces biochemical and
      histological changes in the rabbit brain. The primary histological response to
      this aluminum intoxication is the appearance within many neuronal somata and
      dendrites of intensely argyrophilic masses of fibrillar material. Ultrastructural
      examination of these bodies in both conventionally-prepared and silver-stained
      sections shows them to be composed of neurofilaments. For this reason, we have
      elected to call these argyrophilic masses "neurofilamentous arrays (NFAs)." At
      their zenith, NFAs in cortical pyramidal neurons comprise thousands of filaments
      interconnected by periodic crossbridges. NFAs begin to be formed within both
      somata and dendrites as isolated groups of neurofilaments, which apparently go on
      to assemble en masse within the cytoplasm. In symptomatic animals, many cortical
      neurons are rich in NFAs, yet lack classic cytological signs of degeneration,
      such as nuclear pyknosis. Though silver staining reveals extensive NFAs only in
      aluminum-exposed brains, there is a strong degree of immunostaining for
      phosphorylated neurofilamentous epitopes in both untreated and Al-injected
      animals. This suggests that protein subunits that are already present in the
      neurons under normal circumstances are recruited, in the presence of aluminum, to
      form NFAs through the directed assembly of masses of oriented filaments.

PMID- 11848623
TI  - Pregnancy hormones prevent diabetes and reduce lymphocytic infiltration of islets
      in the NOD mouse.
AB  - Pregnancy is associated with a depression of the immune inflammatory system, and
      with increased growth and function of the pancreatic islets of Langerhans. We
      monitored glucosuria, blood glucose concentration, and lymphocytic infiltration
      of pancreatic islets in 30 female, 10-wk-old, pre-diabetic nonobese diabetic
      (NOD) mice divided into 3 treatment groups for 13 wk: group 1, saline; group 2,
      pregnancy hormones (dexamethasone 4 mg/Kg/day, progesterone 1.7 mg/Kg/day, growth
      hormone 0.6 mg/Kg/day, prolactin 1 mg/Kg/day, and estradiol 0.05 mg/Kg); and
      group 3, prolactin alone (1 mg/Kg/day). At sacrifice, the pancreases were fixed
      in paraformaldehyde and islet infiltration was evaluated. In the saline-treated
      group (#1) 4/10 mice developed diabetes, while in the hormone treated group (#2)
      none of the mice developed diabetes. Only 1/10 mice in the prolactin-treated
      group (#3) developed diabetes during the study. Islets from the hormone cocktail
      treated group were significantly less infiltrated than islets from the other 2
      treatment groups (p <0.001). Thus, the pregnancy hormones protected NOD mice from
      developing diabetes and significantly reduced or eliminated insulitis and islet
      infiltration. Prolactin alone had a partial protective effect. The results have
      implications for prevention of type 1 diabetes and for immune suppression in
      patients receiving islet cell transplantation.

PMID- 11848624
TI  - Familial visceral myopathy with carcinoma of unknown primary.
AB  - We report an autopsy case of a 35-yr-old man with familial visceral myopathy, a
      cause of primary intestinal pseudo-obstruction. The patient died from
      complications of familial visceral myopathy, sepsis, and generalized signet-ring
      cell carcinomatosis. The patient had massive distension of the large and small
      intestines, a dilated thickened esophagus, and fibroneoplastic adhesions between
      intra-abdominal and thoracic structures. This case provides an observation, not
      previously described in cases of familial visceral myopathy, which is fibrosis
      and atrophy of the outer longitudinal smooth muscle of the small bowel,
      alternating to involve only the inner smooth muscle layer of the large bowel.
      This case shows how a malignant neoplasm can compound the pathology of familial
      visceral myopathy.

PMID- 11848625
TI  - Introduction of the cell theory.

PMID- 11848626
TI  - Medicine, government, and capitalism.

PMID- 11848627
TI  - The utility of clinical examination in screening for pelvic fractures in blunt
      trauma.
AB  - BACKGROUND: Current recommendations of the American College of Surgeons Advanced
      Trauma Life Support course is routine radiographic screening of the pelvis for
      all patients who suffer blunt torso trauma. The purpose of this study is to
      evaluate in a prospective manner the sensitivity of clinical examination as a
      screening modality for pelvic fractures in awake and alert blunt trauma patients.
      STUDY DESIGN: During a 32-month period, 2,176 consecutive blunt trauma patients
      who presented with Glasgow Coma Scores of 14 or 15 were evaluated at an urban
      Level I trauma center. Clinical examination of all patients was prospectively
      performed by trauma resident housestaff. The clinical examination of each patient
      was documented in a study form before performance of a standard anterior
      posterior (A-P) pelvic x-ray. RESULTS: We evaluated 2,176 blunt trauma patients,
      97 (4.5%) of whom were diagnosed with pelvic fracture. There were seven missed
      injuries on clinical examination (sensitivity 93%). None of the missed injuries
      on clinical examination required surgical intervention. The sensitivity of A-P
      pelvic x-ray was 87%, with 13 missed injuries. There were 463 patients who
      entered with ethanol levels equal or greater than 100 mg/dL (range 100 to 480
      mg/dL). There were 20 pelvic fractures diagnosed in this group, with only 1
      missed injury on clinical examination (sensitivity 95%). CONCLUSIONS: 1) Clinical
      examination of the pelvis can reliably rule out significant pelvic fracture in
      the awake and alert blunt trauma patient. 2) The addition of routine A-P pelvic x
      ray does not improve the sensitivity in diagnosis of surgically significant
      pelvic fractures nor does it have significant impact on outcomes of pelvic
      fracture patients. 3) Elevated ethanol level is not a contraindication to use of
      clinical examination as a screening modality for pelvic fractures in the awake
      and alert blunt trauma patient.

PMID- 11848628
TI  - The predictive value of laboratory findings in patients with primary
      hyperparathyroidism.
AB  - BACKGROUND: Despite extensive preoperative imaging and intraoperative "gadgetry"
      to facilitate localization of abnormal parathyroid glands, the onus of
      identification and resection remains with the surgeon in the operating room. We
      pondered the relative usefulness of routine laboratory studies to the surgeon as
      predictive guides to the intraoperative findings in patients with primary
      hyperparathyroidism (HPT). STUDY DESIGN: Pre- and postoperative laboratory data
      were analyzed in 166 consecutive patients (1998 to 1999) undergoing successful
      cervical exploration for sporadic primary HPT and were correlated with the
      pathologic findings. Patients with secondary HPT, multiple endocrine neoplasia,
      familial HPT, and parathyroid carcinoma were not included in this study. RESULTS:
      One hundred eighteen women and 48 men (mean age = 63 years) with parathyroid
      adenoma (n = 155) and sporadic hyperplasia (n = 11) were evaluated. Mean
      parathormone (PTH) levels varied little with the pathology: adenoma = 9.6 pmol/L
      and hyperplasia = 10.2 pmol/L (p > 0.05). In patients with parathyroid adenoma,
      analysis of preoperative measures showed a positive correlation (r = 0.48, p <
      0.0001) with PTH and gland weight. The correlation appeared to be the strongest
      in the tails of the distribution; in 22 of 23 (96%) cases with PTH levels lower
      than 6 pmol/L, the offending lesion or lesions were less than 400 mg; in all six
      cases with PTH levels higher than 18.0 pmol/L, the abnormal gland or glands
      weighed more than 800 mg. PTH levels between 6 and 18 pmol/L revealed mean
      adenoma weight of 757 mg (median = 420 mg; range = 50 to 5,500 mg). CONCLUSIONS:
      Extreme values of PTH in patients with single-gland parathyroid disease alert the
      surgeon to the likelihood of small or large parathyroid adenomas. Laboratory
      studies do not differentiate adenoma from hyperplasia, nor do they pinpoint the
      size of abnormal glands with moderate-range PTH values.

PMID- 11848629
TI  - Assessing the predictive value of clinical complete response to neoadjuvant
      therapy for rectal cancer: an analysis of 488 patients.
AB  - BACKGROUND: Patients with transmural or node-positive rectal cancer benefit from
      the addition of chemoradiation to surgical resection. Administration of the
      chemoradiation (combined modality therapy) preoperatively has gained popularity
      in recent years. Some patients undergo apparent complete tumor regression after
      preoperative combined modality therapy, and controversy exists about the proper
      management of these patients. Some investigators have proposed that such patients
      should simply be observed and not undergo resection. STUDY DESIGN: The purpose of
      this study was to determine the significance of clinical complete response to
      preoperative combined modality therapy. Specifically, we have attempted to
      determine the frequency with which a clinical complete response (based on the
      absence of detectable tumor on preoperative digital rectal examination and
      proctoscopy) correlates with a pathologic complete response (based on the absence
      of cancer cells in the resected specimen). A retrospective review of the clinical
      and pathologic characteristics of 488 patients from the Memorial Sloan-Kettering
      prospective colorectal database who received preoperative chemoradiation followed
      by resection for primary rectal cancer was performed. The indications for
      preoperative therapy included clinical or ultrasound T3 or T4 tumors or node
      positive disease. RESULTS: The clinical complete response rate to preoperative
      therapy was 19%. All patients underwent resection subsequent to preoperative
      therapy regardless of response. The pathologic complete response rate among all
      patients was 10%. The pathologic complete response rate among clinical complete
      responders was 25%. Clinical complete response was a significant predictive
      factor for pathologic complete response, but the majority (75%) of clinical
      complete responders had persistent foci of tumor that were not detectable on
      preoperative examination or proctoscopy. CONCLUSIONS: Clinical complete response
      to preoperative therapy as determined by preoperative digital rectal examination
      and proctoscopy or EUA is not an accurate predictor of pathologic complete
      response. A significant percentage of clinical complete responders have
      persistent deep tumors or nodal involvement. We do not recommend making treatment
      decisions based solely on the absence of clinically palpable or visible tumor
      after chemoradiation. Our data suggest that all acceptable-risk patients with a
      diagnosis of primary rectal cancer should undergo resection, regardless of their
      response to preoperative therapy.

PMID- 11848630
TI  - Early gallbladder cancer.
AB  - BACKGROUND: The majority of patients with gallbladder cancer (GBC) have advanced
      disease at the time of diagnosis and are unresectable. Longterm survival is
      usually seen in a subset of patients with early GBC (EGBC)-cancer confined to the
      mucosa (pT1a) and muscularis (pT1b). Management guidelines of EGBC are not yet
      defined and are controversial. The purpose of this article is to evaluate the
      diagnostic aspects and effects of resectional procedures on survival outcome in
      patients with EGBC. STUDY DESIGN: EGBC was defined as cancer confined to the
      mucosa (pT1a) or muscularis (pT1b) according to the TNM classification.
      Clinicopathological details and survival data of 14 patients who had EGBC were
      analyzed. There were 9 women and 5 men, with a mean age of 60 years. RESULTS: A
      definite preoperative diagnosis was possible in only three patients and three
      patients were diagnosed at operation; the majority of patients were diagnosed
      incidentally after cholecystectomy for associated gallstones. Two patients
      underwent extended cholecystectomy and 12 patients underwent simple
      cholecystectomy. Two patients had pT1a and 12 had pT1b lesions. Mean (SD)
      survival was 71.5 (12.2) months and median survival was 42 months. There were
      five treatment failures with locoregional recurrence and death; all with pT1b
      tumors were treated by simple cholecystectomy. Cumulative 1-, 3-, and 5-year
      survival was 92%, 68%, and 68% respectively [corrected]. CONCLUSIONS: Simple
      cholecystectomy is an adequate treatment only for mucosal GBC. Patients with pT1b
      tumors require extended cholecystectomy. Incidental GBC extending up to the
      muscularis merits early reoperation for completion of extended cholecystectomy,
      which offers the only chance of cure.

PMID- 11848631
TI  - Is contrast as bad as we think? Renal function after angiographic embolization of
      injured patients.
AB  - BACKGROUND: Angiographic embolization (AE) is increasingly used to control
      bleeding after severe trauma. Serious concerns have been raised about the safety
      of high-volume i.v. contrast in hypotensive, hypovolemic patients. STUDY DESIGN:
      In a prospective cohort study, 100 consecutive trauma patients underwent AE for
      bleeding in the abdomen and pelvis. Serum creatinine (Cr) levels were measured
      before the procedure and up to 5 days after the procedure. Contrast nephropathy
      was defined as an increase in Cr levels after AE of more than 25% over the
      baseline measurement. An average of 248 +/- 59 mL of nonionic, low-osmolality
      contrast was used in all cases. RESULTS: Compared with the baseline, no increase
      in Cr levels after AE was observed among all patients (1.02 +/- 0.24 versus 0.94
      +/- 0.26 mg/dL; p = 0.01) or among subgroups of patients who had any of the
      following risk factors for renal failure: older than 60 years, Injury Severity
      Score > or = 15, shock on arrival, renal injury, elevated Cr levels (> or = 1.5
      mg/dL) before AE, or administration of a high volume of contrast (> 250 mL).
      Contrast nephropathy developed in five patients by means of mild Cr elevations.
      In all of these patients, Cr returned to baseline within 5 days of AE. Renal
      failure requiring hemodialysis developed at 41 and 55 days after AE in two
      patients with multiple organ failure who eventually died. CONCLUSIONS:
      Administration of nonionic contrast during AE causes mild and transient contrast
      nephropathy in 5% of severely injured patients. Our study adds additional support
      for the safety of AE for trauma.

PMID- 11848632
TI  - Transplantation of crossed fused ectopic kidneys into a single recipient.
AB  - BACKGROUND: Crossed renal ectopia is a rare (1 in 1000 live births) congenital
      anomaly in which both renal masses are located on one side of the abdomen and in
      90% of cases are fused. Although this condition is not typically associated with
      underlying renal pathology or symptoms, complex vascular anatomy is commonly
      encountered. STUDY DESIGN: A report of the successful transplantation of crossed
      fused ectopic kidneys as a single allograft. RESULTS: With careful attention to
      the complex anatomy presented by this anomaly, the course of the patient's
      transplantation and postoperative convalescence were uncomplicated and resulted
      in excellent longterm graft function. We report the first successful
      transplantation and longterm function of crossed fused ectopic kidneys as a
      single allograft. CONCLUSIONS: Given the shortage of cadaveric renal allografts,
      patients with this anomalous condition should not be excluded as potential organ
      donors. Transplant surgeons should have an understanding of this anomaly and its
      anatomic variants to ensure proper utilization of this limited but valuable
      resource.

PMID- 11848633
TI  - Inferior mesenteric artery reimplantation does not guarantee colon viability in
      aortic surgery.
AB  - Reimplantation of the inferior mesenteric artery (IMA) at the time of aortic
      surgery has been advocated to prevent colon ischemia in patients deemed to have
      inadequate perfusion of the left colon. The purpose of this study was to
      determine whether IMA reimplantation is globally protective against colon
      necrosis. We reviewed the medical records of all patients who were diagnosed with
      colon ischemia after aortic surgery during a 10-year period. Cases were indexed
      from the institution's operative database and from the vascular morbidity and
      mortality registry. Ten patients (eight men, two women; mean age 71 +/- 9 years)
      were identified during the study period. Five patients (50%) underwent successful
      IMA reimplantation for inadequate Doppler signals on the antimesenteric border of
      the sigmoid colon. Five other patients (50%) did not undergo IMA reimplantation
      because they were deemed to have adequate colon perfusion. Transmural colon
      necrosis occurred in 6 of the 10 study patients, 4 of whom had IMA
      reimplantation. Five of the six patients had intraoperative hypotension. Three of
      the four patients with colon ischemia presenting less than 24 hours after aortic
      revascularization survived (mortality 25%), but both patients with late colon
      ischemia died of multisystem organ failure (mortality 100%). Four patients
      developed mucosal ischemia and did not undergo colectomy. Only one of these had
      IMA reimplantation. Colon ischemia was detected more than 1 week postoperatively
      in three patients. All four patients were treated with supportive therapy and
      antibiotics, and all four survived to discharge after a mean length of stay of 14
      +/- 10 days. These data show that IMA reimplantation does not ensure colon
      viability in aortic surgery. Transmural colon necrosis tends to present sooner
      than mucosal ischemia and may be attributable to nonanatomic variables such as
      intraoperative hypotension. Although transmural necrosis is a highly morbid
      complication after aortic surgery, timely colectomy may lead to survival in some
      patients.

PMID- 11848634
TI  - What's new in general surgery: burns and metabolism.

PMID- 11848635
TI  - What's new in vascular surgery.

PMID- 11848636
TI  - A working model for the time sequence of genetic changes in breast tumorigenesis.

PMID- 11848637
TI  - Tracheal agenesis.

PMID- 11848638
TI  - The role of tube feeding and total parenteral nutrition in advanced illness.

PMID- 11848639
TI  - Hernia of right colon and cecum through the foramen of Winslow and lesser
      omentum.

PMID- 11848640
TI  - Disseminated hepatic candidiasis.

PMID- 11848641
TI  - Laparoscopic repair of paraostomy hernias: early results.

PMID- 11848642
TI  - The ideal living donor nephrectomy "mini-nephrectomy" through a posterior
      transcostal approach.

PMID- 11848643
TI  - Devascularizations in portal hypertension.

PMID- 11848644
TI  - "Whorl sign" or "whirl sign"?

PMID- 11848645
TI  - Garlic supplements can impede HIV medication.

PMID- 11848646
TI  - NIAID takes next genome step.

PMID- 11848647
TI  - Medical abortion as an alternative to vacuum aspiration: first experiences with
      the 'abortion pill' in The Netherlands.
AB  - OBJECTIVE: To establish to what extent medical abortion is desired as a
      supplement to existing care provision in The Netherlands and to establish the
      (dis)advantages of medical abortion versus surgical vacuum aspiration. METHODS:
      The research project began in November 1999 and ended in September 2000. In two
      abortion clinics, the clients were asked to answer some questions about their
      expectations (before treatment) and their experiences with the treatment (at the
      post-treatment check-up). At the post-treatment check-up, the clients were also
      asked to fill out the Hopkin's Symptom Checklist (HSCL) which is an objective
      measure for the psychological and physical well-being of the clients during the
      previous week. RESULTS: One hundred and thirty-one clients who chose medical
      abortion and 131 clients who chose surgical vacuum aspiration participated in the
      study. The failure rate was 3.3% for medical abortion and 1.5% for surgical
      vacuum aspiration. Of the medical abortion clients, 80.2% reported they were
      satisfied with this treatment and 68.1% said they would choose the same treatment
      procedure in the future. For vacuum aspiration, these figures were 92.9% and
      83.2%, respectively. The most reported advantage of medical abortion was the fact
      that it was a pill, and no surgical procedures were necessary. The most reported
      disadvantages of medical abortion were the amount of blood loss and insecurity
      concerning the time of abortion. CONCLUSIONS: Medical abortion seems to be a good
      supplement to the existing care provision in The Netherlands and should be
      offered in other clinics.

PMID- 11848648
TI  - Treatment of primary and secondary dysmenorrhea with a novel 'frameless'
      intrauterine levonorgestrel-releasing drug delivery system: a pilot study.
AB  - OBJECTIVES: To evaluate the effect on menstrual pain in women with primary and
      secondary dysmenorrhea of a novel 'frameless' intrauterine drug delivery system
      (IUS), FibroPlant-levonorgestrel (LNG) (Contrel Research, Belgium), releasing 14
      microg of LNG per day. An ancillary objective was to evaluate the effect of the
      new IUS on menstrual blood loss. STUDY DESIGN: An open label, non-comparative
      ongoing pilot study. Eighteen insertions were performed in women between 16 and
      52 years of age by the first author. Four insertions were performed in
      nulligravid women. Eight women were categorized as having primary dysmenorrhea
      and 10 as having secondary dysmenorrhea. Twelve women complained of heavy
      bleeding. Three women had significant fibroids and three were suspected to have
      adenomyosis. RESULTS: The trial covers a period from a minimum of 3 months up to
      33 months. By the end of August 2001, 12 recruited women had at least 12 months'
      follow-up and six had between 3 months and 1 year. All women reported much
      reduced pain, or no pain at all, and strongly reduced bleeding which started as
      soon as 1 month after insertion of the FibroPlant-LNG IUS. There was one
      exception; this woman had significant fibroids. She reported much reduced
      bleeding but this was not as pronounced as in the other women in the study. All
      women are continuing to use the method. CONCLUSION: The results of this
      preliminary study suggest that the FibroPlant-LNG IUS, releasing 14 microg ofLNG
      per day, is a safe and effective method for the treatment of primary and
      secondary dysmenorrhea. The absence ofa frame is particularly advantageous in
      these women. Of significant added importance is the high effectiveness in
      reducing menstrual bleeding, a symptom often present in women with menstrual pain
      complaints, and the fact that the system provides effective contraception. The
      low daily release rate of LNG from the FibroPlant-LNG IUS results in a virtual
      absence of hormonal side-effects.

PMID- 11848650
TI  - Contraceptive risk-taking in women and men facing legal abortion.
AB  - OBJECTIVE: The aim of the study was to gain knowledge about contraceptive use,
      reproductive risk-taking and sexuality in Swedish women seeking abortion and
      their partners. METHODS: Two hundred and eleven women and 75 men answered a
      questionnaire before the abortion. The data have been divided into six subgroups:
      women with and without previous experience of abortion, single women and women
      with a partner relationship, and women whose partner participated in the study
      and the male partners. RESULTS: The main findings showed that there are more
      similarities than differences between the subgroups. Overall, there were no
      differences regarding use of contraceptives, sexual life and psychosocial
      characteristics. However, women with previous abortion experience were found to
      be older, had longer partner relationships and more often had children. Some
      gender differences were also found, i.e. women favored coitus-dependent
      contraceptives to a larger extent and took more responsibility for preventing
      unwanted pregnancies. At the time of conception, half the participants had not
      used any contraceptive methods and one-fifth had relied on 'natural family
      planning'. The most common reasons for not using contraceptives were related to
      risk-taking and/or to strong sexual desire. Twelve per cent of the women had felt
      pressure/threat from their partner in connection with the conception. CONCLUSION:
      In efforts to prevent undesired pregnancies, this study highlights the need to
      incorporate a gender perspective both in communication about risk-taking and in
      counselling about contraceptives.

PMID- 11848649
TI  - Body weight change during use of a monophasic oral contraceptive containing 20
      microg ethinylestradiol and 75 microg gestodene with a comparison of the women
      who completed versus those who prematurely discontinued intake.
AB  - OBJECTIVES: Evaluation of the impact of an oral contraceptive on body weight with
      a comparison ofwomen who completed versus women who prematurely discontinued
      intake. METHODS: Data on body weight were retrospectively analyzed from four
      large prospective clinical trials with an oral contraceptive containing 20 microg
      ethinylestradiol and 75 microg gestodene (EE/GSD). A total of 1971 young fertile
      women were included in the evaluation, and 1467 completed 12 cycles. RESULTS: We
      found no clinically relevant change of body weight during treatment with an oral
      contraceptive containing 20 microg ethinylestradiol and 75 microg gestodene in
      the vast majority of users after 12 treatment cycles. The mean change of body
      weight was less than 0.3 kg in this time period for all users. Nearly 70% of
      women experienced a minor change in their body weight of +/- 2 kg. An additional
      13% lost more than 2 kg body weight in the course of 12 treatment cycles. A total
      of 11% increased their weight by 2-4 kg. A total of 1255 (85.5%) of women had a
      body mass index (BMI) of < or = 25 at baseline compared to 1253 (85.4%) after 12
      cycles of treatment. There was no significant difference in the change ofbody
      weight between the women completing 12 cycles of treatment and those who
      prematurely discontinued EE/GSD. CONCLUSIONS: This retrospective analysis
      confirms that there was only a negligible change of body weight during intake of
      an oral contraceptive containing 20 microg ethinylestradiol and 75 microg
      gestodene. There was no difference in weight change between the women completing
      the study or discontinuing intake.

PMID- 11848651
TI  - Contraceptive use and family planning after labor in the European part of the
      Russian Federation: 2-year monitoring.
AB  - OBJECTIVES: To explore the main determinants of the reproductive behavior of
      nursing mothers, all inhabitants of the central part of the European region of
      the Russian Federation, their use of modern contraceptive methods and their
      attitude to future family planning. METHODS: Open cohort multicenter study of
      1200 nursing mothers aged 16-42 years interviewed at 3-5 days' postpartum, with
      subsequent longitudinal monitoring ofthe majority in the local family planning
      centers during the 2 years after labor. RESULTS: The main determinants of the
      reproductive behavior of this cohort of women are an early debut of sexual
      activity, several partners in their reproductive history, relatively early
      marriage with a motivation to have one child in their family and the tendency to
      use induced abortion as one of the methods of birth regulation. Our experience of
      postpartum counselling demonstrated positive changes in the women's attitudes to
      modern contraceptive methods. The data reveal that the induced abortion rate
      among 639 mothers regularly followed-up during the first year postpartum was
      4.4%, and among 606 during the second year was 5.1%. The corresponding rates
      among 129 women who did not visit the family planning centers and who were only
      interviewed 2 years after labor were 9.3% and 8.5%, respectively. CONCLUSIONS:
      Our data show that the unmet needs are remarkably concentrated among women who
      have given birth within the last year or two, and who need augmented attention
      from the family planning and reproductive health services.

PMID- 11848652
TI  - Liver adenoma and focal nodular hyperplasia associated with oral contraceptives.
AB  - We report the case of a woman, with a 15-year history of high-dosage oral
      contraceptive use, who came to our center for a gynecological screening. Elevated
      liver enzymes were detected in blood samples and an abdominal ultrasound showed a
      hypoechogenic nodular image of 8 cm in the right hepatic lobe of the liver.
      Routine examinations, including hepatitis B surface antigen, hepatitis C viral
      antibody and alpha-fetoprotein, were all negative. Imaging studies, including
      computerized tomography scan, magnetic resonance imaging, sulfur colloid
      gammagraphy and hepatic angiography, were performed and confirmed the presence of
      the lesion, detecting the characteristic central scar structure of focal nodular
      hyperplasia. Discontinuation of oral contraceptives and follow-up showed no
      change in lesion size so that a surgical approach was adopted in order to remove
      the hepatocellular carcinoma. Pathological findings confirmed focal nodular
      hyperplasia.

PMID- 11848653
TI  - Intrauterine devices--perceptions overestimate the hazards.

PMID- 11848654
TI  - The connection between media and suicidal behavior warrants serious attention.

PMID- 11848655
TI  - The media as partners in suicide prevention. A column from Befrienders
      International.

PMID- 11848656
TI  - Conscientiousness in childhood and later suicide.

PMID- 11848657
TI  - Grandiose fury. Letter across the Pacific.

PMID- 11848658
TI  - Suicide and the media. Part I: Reportage in nonfictional media.
AB  - Numerous studies have considered the association between media reporting and
      portrayal of suicide and actual suicidal behavior or ideation. This review
      considered 42 studies that have examined the nonfiction media (newspapers,
      television, and books). Consideration was given to the extent to which inferences
      could be made about the relationship between portrayal of suicide in the given
      media and actual suicidal behavior in terms of: the strength of its association;
      and the extent to which it could be considered causal. The review demonstrated
      that there is an association between nonfictional media portrayal of suicide and
      actual suicide. The association satisfies sufficient of the criteria of
      consistency, strength, temporality, specificity and coherence for it to be deemed
      causal.

PMID- 11848659
TI  - Suicide and the media. Part II: Portrayal in fictional media.
AB  - The association between the portrayal of suicide in fictional media and actual
      suicide has been debated since 1774, when it was asserted that Goethe's The
      Sorrows of Young Werther had led people to take their own lives. Since that time,
      a plethora of studies considering the association has been conducted. This review
      considered 34 studies examining the impact of fictional portrayal of suicide (in
      film and television, music, and plays) on actual suicidal behavior. It asked the
      question: "Is there any association, and if so, can it be considered causal?"
      Using strict criteria to establish causality, we found that the evidence was more
      equivocal than was the case for nonfictional reporting.

PMID- 11848660
TI  - Suicide and the media. Part III: Theoretical issues.
AB  - The body of evidence suggests that there is a causal association between
      nonfictional media reporting of suicide (in newspapers, on television, and in
      books) and actual suicide, and that there may be one between fictional media
      portrayal (in film and television, in music, and in plays) and actual suicide.
      This finding has been explained by social learning theory. The majority of
      studies upon which this finding is based fall into the media "effects tradition,"
      which has been criticized for its positivist-like approach that fails to take
      into account of media content or the capacity of audiences to make meaning out of
      messages. A cultural studies approach that relies on discourse and frame analyses
      to explore meanings, and that qualitatively examines the multiple meanings that
      audiences give to media messages, could complement the effects tradition.
      Together, these approaches have the potential to clarify the notion of what
      constitutes responsible reporting of suicide, and to broaden the framework for
      evaluating media performance.

PMID- 11848661
TI  - Mass media, cultural attitudes, and suicide. Results of an international
      comparative study.
AB  - Many studies indicate that the suicidal behavior in a society is affected by the
      suicide stories publicized. Cultural valuations appear in the way media present
      self-destruction. The reflection of sociocultural attitudes toward suicide can be
      observed and analyzed in these texts. In this research, reports about suicide (n
      = 2203) in the years from 1981 and 1991 taken from daily newspapers were gathered
      -three central and regional papers in each country. A content analysis was
      performed of the suicide reports in Hungary (n = 244), Japan (n = 684), the
      United States (n = 265), Germany (former West n = 458, former East n = 60),
      Austria (n = 405), and Finland (n = 81), on the basis of the following variables:
      mentioning of the name, personal data, prominence of the suicidal person,
      qualification of the suicide, methods, motives, positive or negative
      consequences, alternatives, and the expression(s) used to refer to the act. After
      a coding process, an analysis was conducted as to whether any significant
      differences existed in the rate of the several characteristics in the countries
      from the point of view of the possible imitation-identification and of the
      cultural differences are the most important findings interpreted.

PMID- 11848662
TI  - The media and suicide: a cautionary view.
AB  - There is now unequivocal statistical evidence of an association between some
      media portrayals of suicide and further subsequent suicide. However, it is a weak
      association, and it is probably of far less importance than our need to address
      basic principles of good mental health management. Rather than prescribe to the
      media how to report suicide, its potentially positive effects should be
      addressed.

PMID- 11848663
TI  - Clinical oncology clerkship for third-year medical students.
AB  - BACKGROUND: A two-week elective clerkship in clinical oncology is offered to
      third-year medical students. METHODS: Two students at a time participated in the
      rotation and spent time with attendings in a one-to-one setting in outpatient
      clinics in the cancer specialties. The students also attended multidisciplinary
      tumor boards. Grand rounds, peer review conferences, and problem-case conferences
      were attended by the students as well. The students met with an attending for one
      hour, twice-per-week to discuss pertinent oncologic cases and problems. The
      exposure to clinical oncology for two weeks is intended to educate the students
      relative to the presentation, evaluation, treatment, prognosis, and follow-up for
      a variety of cancers. RESULTS: The rotation has been highly successful as
      measured by its popularity and by consistently high course evaluations from the
      medical students. CONCLUSION: The overall quality of the learning experience for
      the rotation has been rated by the students as the highest among all courses in
      their four-year curriculum.

PMID- 11848664
TI  - Four-way test of mortality: a useful tool for cancer education.
AB  - The use of a four-way test for the study of adverse outcomes in cancer, such as
      mortality and relapse, is described. This test facilitates a rapid, structured
      examination of patients' records that has been useful for teaching about the
      actual and apparent causes of treatment failure, and thus useful for teaching
      about how to achieve the best possible outcome for every patient. In this test,
      four questions are asked about factors identified: Was there evidence of 1)
      understaging, and/or 2) undertreatment, and/or 3) other factors, and/or 4) other
      causes? The use of the four-way test is illustrated by a review of 41 consecutive
      patients with Stage I colorectal cancer, 18 of whom had died at the time the
      study was conducted. One or more findings that contributed to either actual or
      apparent treatment failure were readily identified with the four-way test in 17
      of the 18 fatal cases.

PMID- 11848665
TI  - Primary care physicians' attitudes, knowledge, and practices related to cancer
      clinical trials.
AB  - BACKGROUND: Participation of patients in cancer clinical trials is
      disappointingly low and several physician-based factors are thought to be
      responsible. METHODS: In 1998-1999, the National Cancer Institute (NCI) conducted
      a probability survey of three primary care physician groups to gain a better
      understanding of the barriers to clinical-trial patient accrual from their
      perspective. RESULTS: Findings from this survey of 706 primary care physicians
      indicate that the vast majority (98%) refer their patients with cancer to a
      specialist for cancer treatment and rarely bring up the topic of cancer clinical
      trials. Frequently cited reasons for not mentioning clinical trials are
      preferring to leave that discussion to the oncologist (41%) and being unaware of
      any clinical trials that may be available for the patient (37%). CONCLUSION:
      Primary care physicians may represent an important untapped resource for
      introducing the concept of clinical trials as an option to newly diagnosed cancer
      patients.

PMID- 11848666
TI  - Accuracy of cancer-risk assessment in primary care practice.
AB  - BACKGROUND: Primary care physicians (PCPs) are expected to play a central role in
      assessing cancer risk. This study was designed to evaluate how accurately PCPs
      would triage individuals at increased risk for cancer when presented with
      clinical vignettes. METHODS: Surveys evaluated practice demographics, attitudes,
      and responses to clinical scenarios. Answers were compared with guidelines and
      graded for consistency with the risk assessment. RESULTS: PCPs were inaccurate in
      assessing risk (p < 0.0001) and inconsistent in recommending screening (p <
      0.001). Older physicians were more consistent (p < 0.02). No attitudinal bias was
      identified. CONCLUSION: Continuing education of PCPs is important for cancer-risk
      assessment and management.

PMID- 11848667
TI  - Colorectal cancer screening by primary care physicians in Texas: a rural-urban
      comparison.
AB  - BACKGROUND: Little is known about colorectal cancer (CRC) screening practices of
      primary care physicians (PCPs) in rural versus urban locations. METHODS: The
      authors surveyed 3,380 PCP members of the Texas Medical Association (TMA),
      stratified by specialty and rural/urban status. Factors associated with PCPs'
      self-reported practices of CRC screening by fecal occult blood test (FOBT) and/or
      flexible sigmoidoscopy (SIG) were examined using chi-square tests and
      multivariate regression. RESULTS: Over 80% of both rural and urban PCPs reported
      CRC screening with the FOBT, while 70% reported screening with SIG. Many reported
      doing FOBTs in the office versus using the take-home kit. Variations were found
      in recommended ages and screening intervals among all respondents. CONCLUSIONS:
      Geographic location was less important than knowledge and attitudes in predicting
      PCPs' CRC screening practices. More specific education regarding CRC screening
      guidelines needs to be directed towards all PCPs.

PMID- 11848668
TI  - Staying up-to-date through distance education: the radiation therapy perspective.
AB  - BACKGROUND: Distance education (DE) courses are offered to medical radiation
      technologists (therapy) [MRT(T)] in Canada for professional development (PD).
      METHODS: A survey of 300 therapists was conducted to identify potential
      participants and factors that can influence DE participation and learning.
      RESULTS: The motivation to take PD is intrinsic, for personal growth and
      fulfillment, rather than to satisfy employment or provincial requirements. There
      is interest in DE because of its accessibility. Work constraints appear to be
      more restrictive than domestic ones and little support for PD is perceived from
      the cancer centers. CONCLUSIONS: These findings raise implications for
      professional development in cancer centers that are broader than the original
      objective of optimizing course design.

PMID- 11848669
TI  - A province-wide needs assessment of oncology health care professionals in
      psychosocial oncology.
AB  - BACKGROUND: Oncology professionals still lack the knowledge and skills to provide
      effective psychosocial care. Continuing education (CE) aimed at addressing this
      lack may improve the provision of psychosocial care to patients and their
      families. METHODS: The authors conducted a province-wide cross-sectional mail
      survey of oncology health care professionals [oncologists (MDs), nurses (RNs) and
      radiation therapists (RTs)] and assessed psychosocial orientation, self-assessed
      knowledge, and motivation to learn about psychosocial oncology. In addition, they
      sought factors that might influence professionals' willingness to attend CE
      programs. RESULTS: In total, 241 surveys were completed and returned.
      Psychosocial orientation was highest in the RN subgroup. MDs rated their
      knowledge to deal with specific psychosocial issues higher than did RNs and RTs,
      while their motivation to learn more about providing psychosocial care was
      significantly lower. Seventy-three percent of respondents indicated that they
      would like CE in psychosocial oncology. Self-reported motivation to learn was the
      most significant factor associated with this interest. CONCLUSION: These findings
      raise questions about perceived learning needs and aided in the development of an
      interprofessional curriculum in psychosocial oncology.

PMID- 11848670
TI  - Knowledge, attitudes, and practices related to breast cancer screening: a survey
      of Arabic women.
AB  - BACKGROUND: Incorporating breast cancer screening into day-to-day clinical care
      leads to early diagnosis and decreases mortality. Patients' participation in
      screening depends on their knowledge and attitudes, other barriers, and physician
      behavior. METHODS: A cross-sectional questionnaire survey was conducted to
      evaluate knowledge, attitudes, barriers, and practices related to breast cancer
      screening among Arabic women. A convenience sample was selected from 1,750 women
      aged 40-65 years who, for any reason, attended primary health care (PHC) clinics
      in Al-Ain, United Arab Emirates (UAE). RESULTS: Of the 1,750 invited women, 1,445
      agreed to participate; 78 were excluded from analysis because of histories of
      breast cancer. Breast self-examination (BSE) was practiced by 12.7% of the study
      population, clinical breast examination (CBE) by 13.8%, and mammography by 10.3%.
      Knowledge about breast cancer screening was low in the study population. Women
      were infrequently instructed about or offered screening for breast cancer by
      health professionals. Being employed was an independent predictor for
      participation in the three screening examinations. CONCLUSIONS: Health workers
      infrequently offered screening examinations and women lacked adequate knowledge
      about breast cancer screening. Acquired information about barriers to screening
      may help in the design of effective screening programs for Arabic women.

PMID- 11848671
TI  - Impact of a multimedia breast cancer education intervention on use of mammography
      by low-income Latinas.
AB  - BACKGROUND: This paper describes the results of a study of a multimedia breast
      cancer educational intervention for low-education, low-income Latinas. METHODS:
      Study participants were first exposed to an interactive, multimedia breast cancer
      educational intervention and then interviewed four months later to ascertain
      their mammography status. RESULTS: About 40% of the women who had either obtained
      or scheduled mammography since the intervention attributed their decision to the
      intervention. CONCLUSION: Women who had previously been screened and who
      understood that mammography was used as a breast cancer screening method were
      more likely to have scheduled or obtained mammography than other women.

PMID- 11848672
TI  - Bringing breast cancer education to deaf women.
AB  - BACKGROUND: The Deaf community has not been adequately served by mainstream
      public health interventions. METHODS: A breast cancer education program adapted
      for the needs of the Deaf community was evaluated by 123 deaf and hard-of-hearing
      women using pre- and post-surveys and focus groups. RESULTS: Among the findings
      were the difficulty of recruiting Deaf community members to education and
      research programs; low adherence to breast cancer screening guidelines;
      insufficient breast-health knowledge; endorsement of the program; and suggestions
      for strengthening it. CONCLUSION: Deaf women will benefit from breast cancer
      education programs that specifically address their language, culture, and
      preferred learning styles.

PMID- 11848673
TI  - Histoplasma capsulatum molecular genetics, pathogenesis, and responsiveness to
      its environment.
AB  - Histoplasma capsulatum is a thermally dimorphic ascomycete that is a significant
      cause of respiratory and systemic disease in mammals including humans, especially
      immunocompromised individuals such as AIDS patients. As an environmental mold
      found in the soil, it is a successful member of a competitive polymicrobial
      ecosystem. Its host-adapted yeast form is a facultative intracellular pathogen of
      mammalian macrophages. H. capsulatum faces a variety of environmental changes
      during the course of infection and must survive under harsh conditions or
      modulate its microenvironment to achieve success as a pathogen. Histoplasmosis
      may be considered the fungal homolog of the bacterial infection tuberculosis,
      since both H. capsulatum and Mycobacterium tuberculosis exploit the macrophage as
      a host cell and can cause acute or persistent pulmonary and disseminated
      infection and reactivation disease. The identification and functional analysis of
      biologically or pathogenically important H. capsulatum genes have been greatly
      facilitated by the development of molecular genetic experimental capabilities in
      this organism. This review focuses on responsiveness of this fungus to its
      environment, including differential expression of genes and adaptive phenotypic
      traits.

PMID- 11848674
TI  - Four or more species of Cladosporium sympatrically colonize Phragmites australis.
AB  - A collection of Cladosporium has been recovered from common reed growing at Lake
      Constance (Germany). High-resolution cryo-scanning electron microscopy revealed
      that Cladosporium isolates from reed are diverse. Morphologically, we
      distinguished three species, viz. C. herbarum, C. oxysporum, and Cladosporium sp.
      Internal transcribed spacer (ITS) sequence analysis supported these results and,
      moreover, separated the most common species, C. oxysporum, into two subclades.
      Two additional phylogenies were generated to gain support for this finding. The
      first, differentiating fungi by their capacities to metabolize different carbon
      sources, showed correlation with morphology. The second, based on actin gene
      sequences, showed the same overall topology as that of the ITS tree, but resulted
      in a higher resolution indicating the existence of four or more species of
      Cladosporium on reed. A nested PCR assay targeting variable sequences within
      actin introns indicated that these four species sympatrically colonize reed.
      There was no evidence for mutual exclusion on or within the host or
      specialization for host habitats or organs.

PMID- 11848675
TI  - Comparative analysis of sequences expressed during the liquid-cultured mycelia
      and fruit body stages of Pleurotus ostreatus.
AB  - To characterize genes involved in fruit body development, two complementary DNA
      (cDNA) libraries were constructed from RNA isolated from liquid-cultured mycelia
      and fruit bodies of Pleurotus ostreatus. Using single-pass sequencing of cDNA
      clones, 952 and 1069 expressed sequence tags (ESTs) were generated from liquid
      cultured mycelia and fruit body cDNA library, respectively. A BLASTX search
      revealed that 390 of the liquid-cultured mycelia ESTs (41%) and 531 of the fruit
      body ESTs (50%) showed significant similarity to protein sequences described in
      the nonredudant database (E values < or =1 x 10(-5)). When liquid-cultured
      mycelia and fruit body ESTs were compared by the SeqMan II program, among the
      total of 2021 ESTs, 1256 ESTs were unigenes, and 66 unigenes (5.3%) were commonly
      expressed during both stages. The functional catalogs of the ESTs were made by
      comparison with functionally identified Saccharomyces cerevisiae genes. Liquid
      cultured mycelium ESTs were compared with fruit body ESTs and changes of the
      expressed genes during fruit body development were analyzed.

PMID- 11848676
TI  - The genes gmdA, encoding an amidase, and bzuA, encoding a cytochrome P450, are
      required for benzamide utilization in Aspergillus nidulans.
AB  - Two unlinked loci, gmdA and bzuA, have previously been identified as being
      required for the utilization of benzamide as the sole nitrogen source by
      Aspergillus nidulans. We have cloned each of these genes via direct
      complementation. The gmdA gene encodes a predicted product belonging to the
      amidase signature sequence family that displays similarity to AmdS from A.
      nidulans. However, identity is significantly higher to the amdS gene from
      Aspergillus niger. The bzuA gene encodes a protein belonging to the cytochrome
      P450 superfamily and is orthologous to the benzoate para-hydroxylase-encoding
      gene bphA of A. niger. The bzuA1 mutation prevents the use of benzoate as a
      carbon source and intracellular accumulation of benzoate results in growth
      inhibition on benzamide. Northern blot analysis has shown that gmdA expression is
      subject solely to AreA-dependent nitrogen metabolite repression while bzuA is
      strongly benzoate inducible and subject to CreA-mediated carbon catabolite
      repression and a probable inactivation of benzoate induction by glucose.
      Fluorescence microscopy of a fusion of the N-terminal end of BzuA to green
      fluorescent protein revealed that this protein localizes to the endoplasmic
      reticulum.

PMID- 11848677
TI  - Molecular dissection of alleles of the osmotic-1 locus of Neurospora crassa.
AB  - Two-component histidine kinases of bacteria, plants, and fungi are involved in
      the regulation of intracellular events in response to changes in external
      environmental conditions. Fungal histidine kinases play important roles in
      osmoregulation, in vivo and in planta virulence, and sensitivity to certain
      classes of antifungals. The osmotic-1 (OS-1) locus of Neurospora crassa encodes a
      predicted protein with homology to histidine kinases and appears to be an
      osmosensor. Mutants of the OS-1 locus are hypersensitive to salt and are strongly
      resistant to dicarboximide antifungals. Molecular analysis of each of eight OS-1
      mutants revealed that seven resulted from amino acid changes in a domain of the
      protein known as the linker region. These results indicate that the linker region
      of fungal two-component histidine kinases is essential for proper functioning of
      the kinase.

PMID- 11848678
TI  - A transcriptional activator, AoXlnR, controls the expression of genes encoding
      xylanolytic enzymes in Aspergillus oryzae.
AB  - By deletion across the promoter region of the xynF1 gene encoding the major
      Aspergillus oryzae xylanase, a 53-bp DNA fragment containing the XlnR binding
      sequence GGCTAAA as well as two similar sequences was shown to confer xylan
      inducibility on the gene. Complementary and genomic DNAs encoding the Aspergillus
      niger xlnR homologous gene, abbreviated AoxlnR, were cloned from A. oryzae and
      sequenced. AoXlnR comprised 971 amino acids with a zinc binuclear cluster domain
      at the N-terminal region and revealed 77.5% identity to the A. niger XlnR.
      Recombinant AoXlnR protein encompassing the zinc cluster region of the N-terminal
      part bound to both the consensus binding sequence and its cognate sequence,
      GGCTGA, with an approximately 10 times lower affinity. GGCTA/GA is more
      appropriate as the XlnR consensus binding sequence. Both sequences functioned
      independently in vivo in XlnR-mediating induction of the xynF1 gene. This was
      further confirmed by using an AoxlnR disruptant. Neither the xynF1 nor the xylA
      gene was expressed in the disruptant, suggesting that the xylan-inducible genes
      in A. oryzae may also be controlled in the same manner as described for A. niger.

PMID- 11848679
TI  - Ds-like restless deletion derivatives occur in Tolypocladium inflatum and two
      foreign hosts, Neurospora crassa and Penicillium chrysogenum.
AB  - Single copies of the transposon Restless from Tolypocladium inflatum were
      introduced into Neurospora crassa and Penicillium chrysogenum. Excision of
      Restless from its donor site was investigated in N. crassa and in P. chrysogenum
      using direct selective conditions. In N. crassa, forward selection was also
      analyzed. Deleted Restless elements were frequently obtained in addition to the
      expected complete removal of Restless from its donor site. Similar deleted
      elements were also identified in T. inflatum employing a PCR amplification
      strategy. These deleted Restless copies strongly resemble maize Ds elements of
      various types, and direct repeated sequences of 3 to 16 bp were found to flank
      the truncated regions. In addition Ds1-like Restless elements were identified
      that carried foreign sequences between the inverted repeats. We discuss how Ds
      like Restless elements might be generated by inaccurate excision from an active
      transposon copy.

PMID- 11848680
TI  - Insights into Abeta and presenilin from a canine model of human brain aging.
AB  - In this review, we describe insights into beta-amyloid (Abeta) production using
      aged dogs as a model of human brain aging. The advantage of using dogs is that
      they naturally accumulate Abeta neuropathology with age. In parallel, dogs also
      develop age-associated learning and memory impairments. Thus, dogs can complement
      existing transgenic and nonhuman primate models typically used in aging studies.
      Dogs can live up to 18-19 years of age and companion dogs share the same
      environment as humans. Morphological brain changes as a function of age are
      clearly visible in vivo using magnetic image resonance scans. At the light
      microscopic level, dogs accumulate diffuse plaques with a distribution similar to
      that observed in human brain. Confocal studies suggest that Abeta accumulates on
      neuronal membranes in a segregated pattern. This pattern has been confirmed at
      the ultrastructural level using electron microscopy and provides insight into the
      deposition of Abeta into the extracellular space, possibly prior to overt plaque
      formation. Further, double immunogold labeling studies demonstrate that Abeta
      associated with the plasma membrane is colocalized with presenilin. These in vivo
      observations suggest a common site for both Abeta and presenilin supporting the
      hypothesis that the latter is involved with APP processing.

PMID- 11848681
TI  - Cholesterol-dependent gamma-secretase activity in buoyant cholesterol-rich
      membrane microdomains.
AB  - Buoyant membrane fractions containing presenilin 1 (PS1), an essential component
      of the gamma-secretase complex, and APP CTFbeta, a gamma-secretase substrate, can
      be isolated from cultured cells and brain by several different fractionation
      procedures that are compatible with in vitro gamma-secretase assays. Analysis of
      these gradients for amyloid beta protein (Abeta) and CTFgamma production
      indicated that gamma-secretase activity is predominantly localized in these
      buoyant membrane microdomains. Consistent with this localization, we find that
      gamma-secretase activity is cholesterol dependent. Depletion of membrane
      cholesterol completely inhibits gamma-secretase cleavage, which can be restored
      by cholesterol replacement. Thus, altering cholesterol levels may influence the
      development of Alzheimer's disease (AD) by influencing production and deposition
      of Abeta within cholesterol rich membrane microdomains.

PMID- 11848682
TI  - Neurotrophin-3 promotes cell death induced in cerebral ischemia, oxygen-glucose
      deprivation, and oxidative stress: possible involvement of oxygen free radicals.
AB  - To explore the role of neurotrophin-3 (NT-3) during cerebral ischemia, NT-3
      deficient brains were subjected to transient focal ischemia. Conditional mutant
      brains produced undetectable amounts of NT-3 mRNA, whereas the expression of the
      neurotrophin, BDNF, the NT-3 receptor, TrkC, and the nonselective, low-affinity
      neurotrophin receptor p75NTR, were comparable to wild-type. Baseline absolute
      blood flow, vascular and neuroanatomical features, as well as physiological
      measurements were also indistinguishable from wild-type. Interestingly, the
      absence of NT-3 led to a significantly decreased infarct volume 23 h after middle
      cerebral artery occlusion. Consistent with this, the addition of NT-3 to primary
      cortical cell cultures exacerbated neuronal death caused by oxygen-glucose
      deprivation. Coincubation with the oxygen free radical chelator, trolox,
      diminished potentiation of neuronal death. NT-3 also enhanced neuronal cell death
      and the production of reactive oxygen species caused by oxidative damage inducing
      agents. We conclude that endogenous NT-3 enhanced neuronal injury during acute
      stroke, possible by increasing oxygen-radical mediated cell death.

PMID- 11848683
TI  - Coexpression of GSK-3beta corrects phenotypic aberrations of dorsal root ganglion
      cells, cultured from adult transgenic mice overexpressing human protein tau.
AB  - Coexpression of constitutively active GSK-3beta[S9A] rescued the axonal pathology
      induced by overexpression of human tau in transgenic mice (Spittaels et al.,
      (2000) J. Biol. Chem. 275, 41340-41349). We isolated dorsal root ganglion (DRG)
      neuronal cultures from adult tau4R- and tau4R x GSK-3beta-transgenic mice to
      define the mechanisms at the cellular and subcellular level. DRG from tau4R
      transgenics showed a reduced sprouting capacity while density and stability of
      microtubules in the axonal processes were significantly increased. Video-enhanced
      contrast microscopy demonstrated a dramatic inhibition of fast axonal transport.
      Coexpression of GSK-3beta increased tau phosphorylation and reversed the effects
      on microtubule stability and saltatory motion. In DRG from GSK-3beta single
      transgenics, increased tau phosphorylation was evident without any major effects
      on microtubule stability or axonal transport. These observations support the
      hypothesis that excess tau competed with motor-proteins for binding to
      microtubules and/or that a rigid microtubular system inhibits axonal transport.

PMID- 11848684
TI  - Presenilin-dependent gamma-secretase activity modulates neurite outgrowth.
AB  - Demonstration that cleavage of both APP and Notch are dependent on the product of
      the early onset Alzheimer's disease gene, presenilin-1 (PS1), has raised the
      possibility that Notch function may be altered in AD. This finding also suggests
      that Notch may be affected by APPgamma-secretase inhibitors under development for
      the treatment of Alzheimer's disease, as these target PS1. Data that address
      these questions have been lacking, due to inability to specifically modulate PS1
      activity in a system directly relevant to the adult human brain. Using novel
      highly specific inhibitors of PS1/gamma-secretase, we demonstrate that modulation
      of PS1 activity in human CNS neurons not only affects Abeta generation, but also
      has unanticipated effects on Notch and its activity. We demonstrate that
      intracellular trafficking of Notch in human CNS neurons is altered by inhibition
      of PS1 and is accompanied by dramatic changes in neurite morphology, consistent
      with inhibition of Notch activity. These data, together with immunohistochemical
      evidence of elevation of Notch pathway expression in AD brain, suggest that Notch
      dysregulation may contribute to the neuritic dystrophy characteristically seen in
      Alzheimer's disease brain. In addition, they raise the possibility that
      inhibition of gamma-secretase/PS1 may have clinically beneficial effects on the
      neuritic pathology of AD, in addition to its expected effect to reduce amyloid
      burden.

PMID- 11848685
TI  - Alterations in cerebral blood flow and glucose utilization in mice overexpressing
      the amyloid precursor protein.
AB  - We have used quantitative autoradiographic techniques to study the relationship
      between cerebral blood flow (CBF) and glucose utilization (CGU) in two lines of
      transgenic mice overexpressing Swedish mutant amyloid precursor protein (APP) and
      APP-derived Abeta peptides. Mice were studied at an age when there are no amyloid
      plaques. In the 2123 line, CBF was reduced only in telencephalic regions with no
      corresponding decrease in CGU. In 2576 transgenics, a line with higher levels of
      Abeta peptide, both CBF and CGU were reduced throughout the brain. The data
      indicate that Abeta induces alterations in resting CBF that are either associated
      with or independent of alterations in CGU and that occur in the absence of
      amyloid deposition in neuropil of blood vessels. These observations support the
      hypothesis that cerebrovascular and metabolic abnormalities are early events in
      the pathogenesis of Alzheimer's disease.

PMID- 11848687
TI  - Cytomegalovirus is present in a very high proportion of brains from vascular
      dementia patients.
AB  - We previously found that herpes simplex type 1 virus (HSV1), when present in
      brain of carriers of the apolipoprotein E type 4 allele is a strong risk factor
      for Alzheimer's disease. To find if HSV1 or certain other herpesviruses are
      involved in vascular dementia (VaD), we searched post mortem brain specimens from
      patients suffering from VaD for the presence of HSV1, cytomegalovirus (CMV), and
      human herpesvirus type 6 DNA, using polymerase chain reaction. We have found that
      a very high proportion of the VaD patients, 93% (14/15), but not of age-matched
      normals, 34% (10/29), harbor CMV DNA (P = 0.0002); the proportions of the
      patients harboring the other viruses in brain do not differ significantly from
      those of the normals. Further studies are needed to reveal whether or not the
      association of CMV with VaD is causal.

PMID- 11848686
TI  - p38 MAP kinase mediates the cell death induced by PrP106-126 in the SH-SY5Y
      neuroblastoma cells.
AB  - Prion diseases are neurodegenerative pathologies characterized by the
      accumulation in the brain of a protease-resistant form of the prion protein
      (PrP(c)), named PrP(Sc). A synthetic peptide homologous to residues 106-126 of
      PrP (PrP106-126) maintains many PrP(Sc) characteristics. We investigated the
      intracellular signaling responsible for the PrP106-126-dependent cell death of SH
      SY5Y, a cell line derived from a human neuroblastoma. In this cell line, PrP106
      126 induced apoptotic cell death and caused activation of caspase-3, although the
      blockade of this enzyme did not inhibit cell death. The p38 MAP kinase blockers,
      SB203580 and PD169316, prevented the apoptotic cell death evoked by PrP106-126
      and Western blot analysis revealed that the exposure of the cells to the peptide
      induced p38 phosphorylation. Taken together, our data suggest that the p38 MAP
      kinase pathway can mediate the SH-SY5Y cell death induced by PrP106-126.

PMID- 11848688
TI  - Widely spread butyrylcholinesterase can hydrolyze acetylcholine in the normal and
      Alzheimer brain.
AB  - BACKGROUND: Butyrylcholinesterase (BChE), also known as the "pseudo" or "non
      neuronal" cholinesterase, is traditionally thought to have a restricted CNS
      distribution and to play little, if any, role in cholinergic transmission.
      OBJECTIVE: To reanalyze the role of BChE in the human brain with more sensitive
      methodology. METHODS: Three brains were examined with acetylcholinesterase and
      BChE histochemistry. The sections were examined with bright- and dark-field
      microscopy. RESULTS: The histochemical parameters used in the present experiments
      showed that BChE activity was present in all hippocampal and temporal neocortical
      areas known to receive cholinergic input. At all of these locations, the BChE
      enzyme could hydrolyze the acetylcholine surrogate acetylthiocholine. A
      substantial portion of the hippocampal and neocortical BChE appeared to be
      located within neuroglia and their processes. CONCLUSIONS: Butyrylcholinesterase
      may have a greater role in cholinergic transmission than previously surmised,
      making BChE inhibition an important therapeutic goal in Alzheimer's disease. The
      results also suggest that the role of neuroglia in cholinergic transmission may
      be analogous to their well known role in glutamatergic transmission.

PMID- 11848690
TI  - Perspectives of B-mode transcranial ultrasound.
AB  - Transcranial color coded sonography has proved valuable in the diagnostic work-up
      of cerebrovascular disorders in adults. More recently, evidences have converged
      that transcranial sonography is also useful in the diagnosis of brain parenchymal
      disorders. Here, a new field of application is the visualization of signal
      intensity shift in specific brain areas in some neurodegenerative disorders
      (Parkinson's disease, idiopathic dystonia, and depression). Findings obtained by
      transcranial ultrasound complement information from other neuroimaging data in
      these disorders and have led to the generation of new pathophysiological
      concepts. In this review we summarize the application fields of transcranial
      sonography with special emphasis on recent findings in neurodegenerative
      disorders and their implications for future research. As new application and
      processing techniques are being developed transcranial color coded sonography
      will gain increasing impact on both diagnosis and research of neurological
      disorders.

PMID- 11848689
TI  - Low brain histamine content affects ethanol-induced motor impairment.
AB  - The effect of ethanol on motor performance in humans is well established but how
      neural mechanisms are affected by ethanol action remains largely unknown. To
      investigate whether the brain histaminergic system is important in it, we used a
      genetic model consisting of rat lines selectively outbred for differential
      ethanol sensitivity. Ethanol-sensitive rats had lower levels of brain histamine
      and lower densities of histamine-immunoreactive fibers than ethanol-insensitive
      rats, although both rat lines showed no changes in histamine synthesizing
      neurons. Lowering the high brain histamine content of the ethanol-insensitive
      rats with alpha-fluoromethylhistidine before ethanol administration increased
      their ethanol sensitivity in a behavioral motor function test. Higher H3 receptor
      ligand binding and histamine-induced G-protein activation was detected in several
      brain regions of ethanol-naive ethanol-sensitive rats. Brain histamine levels and
      possibly signaling via H3 receptors may thus correlate with genetic differences
      in ethanol-induced motor impairment.

PMID- 11848691
TI  - Changes in blood flow, oxygenation, and volume following extended stimulation of
      rodent barrel cortex.
AB  - Simultaneous optical imaging spectroscopy and laser-Doppler flowmetry were used
      in rodent barrel cortex to examine the hemodynamic response to extended
      electrical stimulation (20 s, 5 Hz) of the whisker pad. Stimulation results in a
      fast early increase in deoxyhemoglobin concentration (Hbr) followed by a later
      decrease to a "plateau" phase approximately 4 s after stimulation onset. There
      was no corresponding decrease in oxyhemoglobin (HbO(2)), which simply increased
      after stimulation, reaching a plateau at approximately 5 s. The time series of
      flow and volume had similar onset times and did not differ significantly
      throughout the presentation of the stimuli. Following stimulation cessation all
      aspects of the hemodynamic response returned to baseline with a long decay
      constant (>20 s), CBV doing so at a slower rate than CBF. The time courses of
      CBF, CBV, Hbr, and HbO(2) were very similar to that produced by a brief stimulus
      up to peak. The relationship between the flow and the volume changes is well
      approximated by the expression CBV = CBF(phi). We find phi to be slightly lower
      under stimulation (0.26 +/- 0.0152) than during hypercapnia (0.32 +/- 0.0172).
      Saturation and flow data were used to estimate changes in CMRO(2) for a range of
      baseline oxygen extraction fractions (OEF). In the case of hypercapnia CMRO(2)
      was biphasic, increasing after onset and sharply decreasing below baseline
      following cessation. If it is assumed that there is no "net" increase in CMRO(2)
      (i.e., SigmaDeltaCMRO(2) = 0) following the onset and offset of hypercapnia, then
      the corresponding estimate of baseline OEF is 0.45. Evidence for increased oxygen
      consumption was obtained for all stimulation intensities assuming a baseline OEF
      of 0.45.

PMID- 11848692
TI  - Experimental design and the relative sensitivity of BOLD and perfusion fMRI.
AB  - This paper compares the statistical power of BOLD and arterial spin labeling
      perfusion fMRI for a variety of experimental designs within and across subjects.
      Based on theory and simulations, we predict that perfusion data are composed of
      independent observations in time under the null hypothesis, in contrast to BOLD
      data, which possess marked autocorrelation. We also present a method (sinc
      subtraction) of generating perfusion data from its raw source signal that
      minimizes the presence of oxygen-sensitive signal changes and can be used with
      any experimental design. Empirically, we demonstrate the absence of
      autocorrelation in perfusion noise, examine the shape of the hemodynamic response
      function for BOLD and perfusion, and obtain a measure of signal to noise for each
      method. This information is then used to generate a model of relative sensitivity
      of the BOLD and perfusion methods for within-subject experimental designs of
      varying temporal frequency. It is determined that perfusion fMRI provides
      superior sensitivity for within-subject experimental designs that concentrate
      their power at or below approximately 0.009 Hz (corresponding to a "blocked"
      experimental design of 60-s epochs). Additionally, evidence is presented that
      across-subject hypothesis tests may be more sensitive when conducted using
      perfusion imaging, despite the better within-subject signal to noise obtained in
      some cases with BOLD.

PMID- 11848693
TI  - The role of the basal forebrain in episodic memory retrieval: a positron emission
      tomography study.
AB  - Human lesion data indicate that the basal forebrain or orbitofrontal cortex, or
      both, as well as medial temporal and diencephalic structures, is important for
      normal memory and that its disruption causes the pure amnesic syndrome, in which
      episodic memory is grossly impaired while other kinds of memory remain preserved.
      Among these critical areas, functional imaging studies have so far failed to
      detect activation of the basal forebrain, although activation in the nearby
      orbitofrontal cortex has been reported during episodic memory retrieval. We
      employed positron emission tomography to elucidate the neural basis of episodic
      memory recall utilizing two types of time cues and successfully detected activity
      in the basal forebrain for the first time. Specifically, recall of previously
      memorized words from temporal cues was associated with activity in the basal
      forebrain, right middle frontal gyrus, right superior temporal gyrus, and
      posterior cingulate gyrus, whereas their recall from person cues was associated
      with activity in the left insula, right middle frontal gyrus, and posterior
      cingulate gyrus. Furthermore, percentage increases of regional blood flow in the
      basal forebrain were correlated with behavioral data of successful recall. Our
      results provide clear evidence that the human basal forebrain has a specific role
      in episodic memory recall, especially that from time-contextual information.

PMID- 11848694
TI  - Magnetoencephalographic correlates of audiotactile interaction.
AB  - To seek for correlates of an interaction between auditory and somatosensory
      processing, the brain's magnetic field in response to simultaneously presented
      auditory (A) and tactile (T) stimuli was compared with the sum of the respective
      unimodal responses (A+T). The stimuli were binaural 1047-Hz tone bursts of 60 dB
      sensation level and tactile pressure pulses to the right thumb. The mean interval
      between two stimuli of the same modality was 1.95 s. The magnetic field was
      recorded using a 306-channel whole-scalp neuromagnetometer. A clear audiotactile
      interaction was revealed in the hemisphere contralateral to the side of tactile
      stimulation in six of eight subjects, whereas in the ipsilateral hemisphere an
      interaction was noticed in only three subjects. The time courses of these
      audiotactile interaction fields typically showed major deflections of opposite
      polarities around 140 and 220 ms. The first deflection appeared to arise in the
      region of the secondary somatosensory cortex (SII). The polarity of this
      interaction was consistent with the view that the auditory stimulus resulted in a
      partial inhibition in SII. In two subjects, strong indications of auditory
      contributions to the interaction were available, although in different
      hemispheres. The relatively high interindividual variability of the observed
      interaction, which represents potential neural substrates for multisensory
      integration, could indicate that the way subjects perceive the simultaneous
      presentation of auditory and tactile stimuli differs.

PMID- 11848695
TI  - The role of frontopolar cortex in subgoal processing during working memory.
AB  - Neuroimaging studies have implicated the anterior-most or frontopolar regions of
      prefrontal cortex (FP-PFC, e.g., Brodmann's Area 10) as playing a central role in
      higher cognitive functions such as planning, problem solving, reasoning, and
      episodic memory retrieval. The current functional magnetic resonance imaging
      (fMRI) study tested the hypothesis that FP-PFC subserves processes related to the
      monitoring and management of subgoals, while maintaining information in working
      memory (WM). Subjects were scanned while performing two variants of a simple
      delayed response WM task. In the control WM condition, subjects monitored for the
      presence of a specific concrete probe word (LIME) occurring following a specific
      abstract cue word (FATE). In the subgoal WM condition, subjects monitored for the
      presence of any concrete probe word immediately following any abstract cue word.
      Thus, the task required semantic classification of the probe word (the subgoal
      task), while the cue was simultaneously maintained in WM, so that both pieces of
      information could be integrated into a target determination. In a second control
      condition, subjects performed abstract/concrete semantic classification without
      WM demands. A region within right FP-PFC was identified which showed significant
      activation during the subgoal WM condition, but no activity in either of the two
      control conditions. However, this FP-PFC region was not modulated by direct
      manipulation of active maintenance demands. In contrast, left dorsolateral PFC
      was affected by active maintenance demands, but the effect did not interact with
      the presence of a subgoal task. Finally, left ventral PFC regions showed
      activation in response to semantic classification, but were not affected by WM
      demands. These results suggest a triple dissociation of function within PFC
      regions, and further indicate that FP-PFC is selectively engaged by the
      requirement to monitor and integrate subgoals during WM tasks.

PMID- 11848696
TI  - Correlations between structural CNS damage and functional MRI changes in primary
      progressive MS.
AB  - In patients with primary progressive multiple sclerosis (PPMS), we investigated
      whether brain and cervical cord structural changes in lesions and normal
      appearing brain tissue (NABT), measured using conventional, magnetization
      transfer (MT), and diffusion tensor (DT) MRI, are correlated with movement
      associated cortical activations measured using functional magnetic resonance
      imaging (fMRI). From 26 right-handed PPMS patients and 15 right-handed, sex- and
      age-matched healthy controls, we obtained: (a) brain and cervical cord dual-echo
      scans and MT ratio (MTR) maps; (b) brain mean diffusivity (D(-)) maps, and (c) f
      MRI (flexion-extension of the last four fingers of the right hand). All PPMS
      patients had no previous symptoms affecting their right upper limbs, which were
      functionally normal. Healthy volunteers showed more significant activation in the
      ipsilateral cerebellar hemisphere than PPMS patients. PPMS patients showed
      greater activation bilaterally in the superior temporal gyrus, ipsilaterally in
      the middle frontal gyrus, and, contralaterally in the insula/claustrum. In PPMS
      patients, moderate to strong correlations (r values ranging from 0.59 to 0.68)
      were found between relative activations of cortical areas located in a widespread
      network for sensory-motor and multimodal integration and the severity of
      structural changes of the NABT (as measured using MT and DT MRI) and the severity
      of cervical cord damage (as measured using MT MRI). This study shows that the
      pattern of cortical activation of PPMS patients is different from that of normal
      controls even when performing a motor task with clinically unaffected limbs. It
      also suggests that cortical reorganization might be able to limit the
      consequences of MS injury in the brain and cervical cord.

PMID- 11848697
TI  - Widespread dorsal stream activation during a parametric mental rotation task,
      revealed with functional magnetic resonance imaging.
AB  - Following a parametrically modulated mental rotation task, in which 10 healthy
      subjects were instructed to determine whether alphanumeric characters were normal
      or mirror-reversed, bilateral dorsal stream activations culminating in the
      intraparietal region were revealed with functional magnetic resonance imaging.
      Although the parietal activations were bilateral, we observed a right hemispheric
      dominance for the task, consistent with our previous findings (I. M. Harris et
      al., 2000). By studying individual activation maps in response to the paradigm,
      we discerned parcellation of the intraparietal region into discrete subdivisions.
      In this paper, we address the involvement of structures surrounding the
      intraparietal sulcus in mental rotation, as well as describing a wider
      visuospatial attentional network, encompassing neural substrates within the
      dorsal stream.

PMID- 11848698
TI  - Functional magnetic resonance imaging correlates of fatigue in multiple
      sclerosis.
AB  - Although fatigue is a common and troublesome symptom of multiple sclerosis (MS),
      its pathogenesis is poorly understood. In this study, we used functional magnetic
      resonance imaging (fMRI) to test whether a different pattern of movement
      associated cortical and subcortical activations might contribute to the
      development of fatigue in patients with MS. We obtained fMRI during the execution
      of a simple motor task with completely normally functioning hands from 15 MS
      patients with fatigue (F), 14 MS patients without fatigue (NF), and 15 sex- and
      age-matched healthy volunteers. F and NF MS patients were also matched for major
      clinical and MRI variables. FMRI data were analyzed using statistical parametric
      mapping. In all patients, severity of fatigue was rated using the Fatigue
      Severity Scale (FSS). Compared to healthy subjects, MS patients showed more
      significant activations of the contralateral primary somatomotor cortex, the
      contralateral ascending limb of the Sylvian fissure, the contralateral
      intraparietal sulcus (IPS), the contralateral supplementary motor area, and the
      ipsilateral and contralateral cingulate motor area (CMA). Compared to F MS
      patients, NF patients showed more significant activations of the ipsilateral
      cerebellar hemisphere, the ipsilateral rolandic operculum, the ipsilateral
      precuneus, the contralateral thalamus, and the contralateral middle frontal
      gyrus. In contrast, F MS patients had a more significant activation of the
      contralateral CMA. Significant inverse correlations were found between FSS scores
      and relative activations of the contralateral IPS (r = -0.63), ipsilateral
      rolandic operculum (r = -0.61), and thalamus (r = -0.62). This study provides
      additional evidence that fatigue in MS is related to impaired interactions
      between functionally related cortical and subcortical areas. It also suggests
      that fMRI might be a valuable tool to monitor the efficacy of treatment aimed at
      reducing MS-related fatigue.

PMID- 11848699
TI  - A new method to identify multiple sources of oscillatory activity from
      magnetoencephalographic data.
AB  - Identifying the sources of oscillatory activity in the human brain is a
      challenging problem in current magnetoencephalography (MEG) and
      electroencephalography (EEG) research. The fluctuations in phase and amplitude of
      cortical oscillations preclude signal averaging over successive sections of the
      data without a priori assumptions. In addition, several sources at different
      locations often produce oscillatory activity at similar frequencies. For example,
      spontaneous oscillatory activity in the 8- to 13-Hz band is produced
      simultaneously at least in the posterior parts of the brain and bilaterally in
      the sensorimotor cortices. The previous approaches of identifying sources of
      oscillatory activity by dipole modeling of bandpass filtered data are quite
      laborious and require that multiple criteria are defined by an experienced user.
      In this work we introduce a convenient method for source localization using
      minimum current estimates in the frequency domain. Individual current estimates
      are calculated for the Fourier transforms of successive sections of continuous
      data. These current estimates are then averaged. The algorithm was tested on
      simulated and measured MEG data and compared with conventional dipole modeling.
      The main advantage of the proposed method is that it provides an efficient
      approach for simultaneous estimation of multiple sources of oscillatory activity
      in the same frequency band.

PMID- 11848700
TI  - Visually evoked gamma responses in the human brain are enhanced during voluntary
      hyperventilation.
AB  - Hypocapnia induced by hyperventilation (HV) has powerful effects on neuronal
      excitability and synaptic transmission. We have studied the effect of
      hyperventilation on the phase-locked oscillatory components of the evoked
      responses in the human brain. We recorded visually evoked magnetoencephalographic
      responses before, during, and after voluntary hyperventilation to pattern
      reversal checkerboard stimuli. Gamma-band (30-45 Hz) responses phase-locked to
      the stimuli were generated in the occipital visual cortex. A wavelet-based time
      frequency analysis revealed that the gamma responses increased during HV whereas
      their frequency did not change significantly. A recent in vitro study in the rat
      hippocampus demonstrated that the stability of spontaneous gamma activity
      increases during hypocapnia as a result of enhanced GABAergic transmission. To
      test if a similar mechanism could account for our findings, we performed
      simulations on a network of 100 Hodgkin-Huxley neurons connected by inhibitory
      synapses. We found that enhanced GABA(A) transmission, paired with enhanced
      excitability, can explain the increase in evoked gamma activity without changing
      the frequency.

PMID- 11848701
TI  - A role for the ventral visual stream in reporting movements.
AB  - In this experiment we contrast the neural activity associated with reporting a
      stimulus attribute with the activity that occurs when the same stimulus attribute
      is used to guide behavior. Reporting the characteristics of a stimulus differs
      from simply tracking that stimulus since reporting requires that a stimulus is
      explicitly recognized and associated with an arbitrary response. In one condition
      the subject used his right finger to follow a square that moved randomly on a
      screen. In a second condition he had to indicate changes in the direction of the
      square's movements by touching one of two report buttons with his right finger.
      Two other conditions were added to control for the differences in the form of
      movement between the two primary conditions. When the reporting condition was
      contrasted with the tracking condition (controlling for the differences in the
      form of movement), areas in the ventral visual system (the left ventral
      prefrontal cortex and the left inferior temporal cortex) were activated. This
      study shows that contrasting a manual task which involves a report with a manual
      task which does not activates the ventral visual system. However, the observation
      of additional activity in other areas suggests that, while activity in the
      ventral stream is necessary for reporting, it is not sufficient.

PMID- 11848702
TI  - Experiencing oneself vs another person as being the cause of an action: the
      neural correlates of the experience of agency.
AB  - The present study is aimed at identifying the neural correlates of two kinds of
      attribution: experiencing oneself as the cause of an action (the sense of agency)
      or experiencing another person as being the cause of that action. The
      experimental conditions were chosen so that they differed only in their
      requirement to attribute an action to another person or to oneself. The same
      motor task and the same visual stimuli were used in the experimental conditions.
      Subjects used a joystick to drive a circle along a T-shaped path. They were told
      that the circle would be driven either by themselves or by the experimenter. In
      the former case subjects were requested to drive the circle, to be aware that
      they drove the circle, and thus to mentally attribute the action seen on the
      screen to themselves. In the latter case they were also requested to perform the
      task, but they were aware that action seen on the screen was driven by the
      experimenter. In accord with previous studies, the results showed that being
      aware of causing an action was associated with activation in the anterior insula,
      whereas being aware of not causing the action and attributing it to another
      person was associated with activation in the inferior parietal cortex. These two
      regions are involved in the perception of complex representations of the self and
      of its interactions with the external world. We suggest that the anterior insula
      is concerned with the integration of all the concordant multimodal sensory
      signals associated with voluntary movements. The inferior parietal cortex, in
      contrast, represents movements in an allocentric coding system that can be
      applied to the actions of others as well as the self.

PMID- 11848703
TI  - Magnetization transfer ratio in mild cognitive impairment and dementia of
      Alzheimer's type.
AB  - Almost half of the elderly subjects that are diagnosed with mild cognitive
      impairment (MCI) go on to develop dementia of Alzheimer's type (DAT) over a 5
      year follow-up. MCI and DAT subjects show regional decreases in the volume of
      brain structures, which correlate with the cognitive decline among these groups.
      Volumetric changes are found more consistently in the DAT group than in the MCI
      group. Since not all MCI subjects demonstrate volumetric decline, we propose that
      the underlying changes in the structural integrity of the brain, measured using
      magnetization transfer ratio (MTR), may be used as an additional predictor for
      abnormal cognitive decline in the elderly. Magnetic resonance (MR) images were
      obtained in 15 DAT, MCI, and elderly control subjects. Using automatic tissue
      classification, the brain region of each MR volume was segmented into gray matter
      and white matter. Mean and standard error of the mean MTR measured within the
      gray matter was found to be significantly lower in the MCI (30.77 +/-0.29; P =
      0.037) and the DAT (29.37 +/-0.41; P = 0.000) group compared to the control group
      (32.11 +/-0.20). The MTR of white matter was significantly lower only in the DAT
      group. The gray matter volume was significantly lower (P = 0.000) in the DAT
      (387.29 +/-26.04 cm(3)) group compared to controls (532.93 +/-20.53 cm(3)) and
      MCI (464.64 +/-16.93 cm(3)). No significant differences were found in the white
      matter volume between the three groups. We conclude that changes in MTR are
      measurable even in the absence of detectable volumetric changes in gray and white
      matter in the MCI group. Furthermore, MTR changes may present a novel MRI measure
      for the early diagnosis of dementia of Alzheimer's type.

PMID- 11848704
TI  - The effects of interdistracter similarity on search processes in superior
      parietal cortex.
AB  - The superior parietal lobe has been associated with the spatial integration of
      visual features, an important step in the detection of particular form
      conjunctions. However, behavioral research has indicated that when target items
      can be segmented from neighboring distracters via similarity grouping, detection
      may not rely on spatial integration. The question therefore arises as to whether
      the superior parietal cortex is an integral component of conjunction search or
      only important in the absence of certain grouping relations. Here, we acquired
      measures of reaction time and event-related fMRI, while subjects searched for
      conjunction targets in displays containing either homogeneous or heterogeneous
      distracters. We confirm that under conditions of low distracter similarity,
      search involves parietal-motor areas associated with spatial selection. However,
      we also demonstrate that under conditions of high distracter similarity, search
      is instead associated with activation of right temporal-parietal cortex. These
      results suggest that the superior parietal cortex is not a necessary component of
      visual conjunction search and highlight a new role for the right temporal
      parietal cortex in perceptual grouping.

PMID- 11848706
TI  - Spatial nitric oxide imaging using 1,2-diaminoanthraquinone to investigate the
      involvement of nitric oxide in long-term potentiation in rat brain slices.
AB  - Long-term potentiation (LTP), a model of activity-dependent synaptic plasticity,
      involves the persistent enhancement of excitatory neurotransmission. Several
      recent studies have suggested a critical role for nitric oxide (NO) production in
      hippocampal LTP. However, increase in NO production in living tissue has not yet
      been directly demonstrated. We used 1,2-diaminoanthraquinone (DAQ) to demonstrate
      NO production in rat brain slices in relation to induction of LTP. DAQ was found
      to be without neurotoxic effects and it neither influenced normal evoked field
      potential amplitudes nor did it affect induction of LTP in comparison to
      controls. We found that DAQ-induced fluorescence is elevated within a limited
      area of about 40,000 microm(2) during LTP induction in the hippocampal area CA1.
      Furthermore, we could demonstrate that application of the NO-synthetase inhibitor
      l-NAME inhibits the induction of LTP in area CA1 and causes a strong reduction of
      DAQ induced fluorescence. Our results are consistent with the hypothesis that NO
      can serve as a retrograde messenger during induction of LTP in the hippocampus.

PMID- 11848705
TI  - A database of [(11)C]WAY-100635 binding to 5-HT(1A) receptors in normal male
      volunteers: normative data and relationship to methodological, demographic,
      physiological, and behavioral variables.
AB  - PET studies of [(11)C]WAY-100635 binding are proving to be a useful tool to
      evaluate 5-HT(1A) receptor function in vivo in humans. We describe the pattern of
      [(11)C]WAY-100635 binding in 61 healthy male brains and examine its variability.
      For all PET scans, binding potential (BP) values for [(11)C]WAY-100635 in
      different regions were calculated using a simplified reference tissue model, with
      the cerebellum as reference region. Specifically we describe (1) region of
      interest and SPM databases of PET [(11)C]WAY-100635 binding, including test
      retest variability; (2) the sensitivity of [(11)C]WAY-100635 binding to
      manipulations of endogenous 5-HT; and (3) correlations between [(11)C]WAY-100635
      binding and radiochemical, demographic, physiological, and behavioral variables.
      The regional distribution of [(11)C]WAY-100635 binding in healthy human brain was
      similar to that reported in vitro. The test-retest variability was approximately
      12% (range 9-16%) and was similar for all methods of regional sampling. The
      binding of [(11)C]WAY-100635 was insensitive to changes in brain 5-HT induced by
      tryptophan infusion and depletion. Although BP values varied greatly across
      subjects (range 2.9-6.8), there were no significant correlations of regional and
      global BP with common radiochemical, demographic, physiological, and personality
      variables. Specifically, in contrast with two recent small studies, we found no
      decline of [(11)C]WAY-100635 binding with age in our large cohort over the age
      range of 24 to 53 years. Assessment of 5-HT(1A) receptors in vivo using PET and
      [(11)C]WAY-100635 gives reliable measures of 5-HT(1A) binding. The large between
      subject variability observed could not be explained by common methodological,
      physiological, or behavioral factors and hence the biological basis of this
      variability remains to be clarified.

PMID- 11848707
TI  - Modulated activation of the human SI and SII cortices during observation of hand
      actions.
AB  - Neurons in area F5 of the monkey premotor cortex are activated during both
      execution and observation of hand actions. A similar "mirror-neuron system" seems
      to exist also in the human brain, including at least the superior temporal sulcus
      region, Broca's area, and the primary motor cortex. We recorded somatosensory
      evoked fields in response to median nerve stimulation from nine healthy subjects
      during (i) rest, (ii) manipulation of a small object, and (iii) observation of
      the same action to find out to what extent the somatosensory cortices display
      behavior similar to the human mirror-neuron system. SI signals were enhanced and
      SII signals suppressed during both manipulation and observation, except when the
      right manipulating hand was stimulated. Our results suggest that the SI and SII
      cortices contribute to the human mirror-neuron system, possibly providing
      information necessary for preserving the sense of self during action observation.

PMID- 11848708
TI  - An fMRI study of bilingual sentence comprehension and workload.
AB  - To examine the relation between the cortical substrates that support the
      comprehension of one's native language and those that support a second language,
      fMRI measures of cortical activation were taken as native Japanese participants,
      who had acquired moderate fluency in English, listened to auditory sentences in
      Japanese and English. In addition, to examine the impact of processing difficulty
      within a language, sentence difficulty was manipulated by including affirmative
      (easy) and negative (hard) sentences. The volume of activation was greater for
      English in most of the cortical regions, suggesting that more cognitive effort
      was required to process English. Also, a high percentage of the voxels that were
      activated for the Japanese condition were also activated for the English
      condition, with as much overlap between Japanese and English as between the
      processing of affirmative and negative sentences within Japanese. Negative
      sentences elicited greater activation than affirmative sentences primarily for
      English, indicating that the structural difficulty of negation has a larger
      impact on cortical activation if it occurs in the context of the second language,
      which may serve as another source of difficulty. These results suggest that a
      shared network of cortical regions supports the processing of both a first and a
      second language, such that the second language requires more computation and
      activity from the network.

PMID- 11848709
TI  - Abnormal functional connectivity in posttraumatic stress disorder.
AB  - This study investigated the efficacy of a combined multivariate/resampling
      procedure for the analysis of PET activation studies. The covariance-based
      multivariate analysis was used to investigate distributed brain systems in
      posttraumatic stress disorder (PTSD) patients and matched controls during
      performance of a working memory task. The results were compared to univariate
      results obtained in an earlier study. We also examined whether the PTSD patients
      demonstrated a breakdown in functional connectivity that may be associated with
      working memory difficulties often experienced by these patients. A resampling
      procedure was used specifically to test the reliability of measured between-group
      effects, to avoid mistaken inference on the basis of random intersubject
      differences. Significant and reproducible differences in network connectivity
      were obtained for the two groups. The functional connectivity pattern of the
      patient group was characterized by relatively more activation in the bilateral
      inferior parietal lobes and the left precentral gyrus than the control group, and
      less activation in the inferior medial frontal lobe, bilateral middle frontal
      gyri and right inferior temporal gyrus. The resampling procedure provided direct
      evidence that working memory updating was abnormal in PTSD patients relative to
      matched controls. This work focuses on the need to identify extended brain
      networks (in addition to regionally specific changes) for the full
      characterization of brain responses in neuroimaging experiments. Our multivariate
      analysis explicitly measures the reliability of the patterns of functional
      connectivity we obtain and demonstrates the potential of such analyses for the
      study of brain network dysfunction in psychopathology.

PMID- 11848710
TI  - Anatomic constraints on cognitive theories of category specificity.
AB  - Many cognitive theories of semantic organization stem from reports of patients
      with selective, category-specific deficits for particular classes of objects
      (e.g., fruit). The anatomical assumptions underlying the competing claims can be
      evaluated with functional neuroimaging but the findings to date have been
      inconsistent and insignificant when standard statistical criteria are adopted. We
      hypothesized that category differences in functional brain responses might be
      small and task dependent. To test this hypothesis, we entered data from seven PET
      studies into a single multifactorial design which crossed category (living vs man
      made) with a range of tasks. Reliable category-specific effects were observed but
      only for word retrieval and semantic decision tasks. Living things activated
      medial aspects of the anterior temporal poles bilaterally while tools activated a
      left posterior middle temporal region. These category-by-task interactions
      provide robust evidence for an anatomical double dissociation according to
      category and place strong constraints on cognitive theories of the semantic
      system. Furthermore they reconcile some of the apparent inconsistencies between
      lesion studies and functional neuroimaging data.

PMID- 11848711
TI  - Left-hemisphere-dominant SII activation after bilateral median nerve stimulation.
AB  - We used bilateral median nerve stimuli to find out possible hemispheric dominance
      in the activation of the second somatosensory cortex, SII. Somatosensory evoked
      fields (SEFs) were recorded from 14 healthy adults (7 right-handed, 7 left
      handed) with a 306-channel neuromagnetometer. Electrical stimuli were applied
      once every 3 s simultaneously either to the left and right median nerves at the
      wrists or to the palmar skin of both thumbs. Sources of SEFs were modeled with
      four current dipoles, located in the SI and SII cortices of both hemispheres. The
      SI activation strengths did not differ between the hemispheres, whereas the SII
      responses were significantly stronger in the left than in the right hemisphere.
      In right-handers, the left/right SII ratios were 1.9 and 1.8 for wrist and thumb
      stimuli, respectively. The corresponding values were 1.5 and 1.7 in left-handers.
      The results indicate handedness-independent functional specialization of the
      human SII cortices.

PMID- 11848712
TI  - Cortical activation associated with passive movements of the human index finger:
      an MEG study.
AB  - We recorded somatosensory evoked fields to passive extensions of the left and
      right index fingers in eight healthy adults. A new nonmagnetic device was
      designed to produce calibrated extensions of 19 degrees, with a mean angular
      velocity of 630 degrees/s. The responses, recorded with a 306-channel
      neuromagnetometer, were modeled with current dipoles. The earliest activation was
      in the primary somatosensory cortex, with peaks at 36-58 and 30-82 ms for left
      and right index finger extensions, respectively. Later signals were observed in
      the left second somatosensory (SII) cortex in six of eight subjects at 75-175 and
      75-155 ms for left- and right-sided extensions, respectively; three subjects
      showed bilateral SII activation in at least one condition. Our results suggest a
      predominant role for the human left SII cortex in proprioceptive processing.

PMID- 11848713
TI  - Improved parametric image generation using spatial-temporal analysis of dynamic
      PET studies.
AB  - The value of parametric images that represent both spatial distribution and
      quantification of the physiological parameters of tracer kinetics has long been
      recognized. However, the inherent high noise level of pixel kinetics of dynamic
      PET makes it unsuitable to generate parametric images of the microparameters of
      tracer kinetic model by conventional weighted nonlinear least squares (WNLS)
      fitting. Based on the concept that both spatial and temporal information should
      be integrated to improve parametric image quality, a nonlinear ridge regression
      with spatial constraint (NLRRSC) parametric imaging algorithm was proposed in
      this study. For NLRRSC, a term that penalizes local spatial variation of
      parameters was added to the cost function of WNLS fitting. The initial estimates
      and spatial constraint were estimated by component representation model (CRM)
      with cluster analysis. A hierarchical cluster with average linkage method was
      used to extract components. The ridge parameter was determined by linear ridge
      regression theory at each iteration, and a modified Gauss-Newton algorithm was
      used for minimizing the cost function. Results from a computer simulation showed
      that the percent mean square error of estimates obtained by NLRRSC can be
      decreased by 60-80% compared to that of WNLS. The parametric images estimated by
      NLRRSC are significantly better than the ones generated by WNLS. A highly
      correlated linear relationship was found between the ROI values calculated from
      the microparametric images generated by NLRRSC and estimates from ROI kinetic
      fitting. NLRRSC provided a reliable estimate of glucose metabolite uptake rate
      with a comparable image quality compared to Patlak analysis. In conclusion,
      NLRRSC is a reliable and robust parametric imaging algorithm for dynamic PET
      studies.

PMID- 11848714
TI  - Microstructural but not macrostructural disruption of white matter in women with
      chronic alcoholism.
AB  - The results of in vivo neuroimaging studies assessing whether and where brain
      white matter damage occurs in alcoholic women is controversial. To address this
      controversy, we examined regional white matter macrostructure and microstructure,
      the latter of which may be more sensitive to the detection of subtle fiber
      disruption than gross measures of size. Accordingly, we used conventional
      magnetic resonance imaging (MRI) to quantify regional callosal size and diffusion
      tensor imaging (DTI) to examine intravoxel coherence (fractional anisotropy, FA)
      and intervoxel coherence (C) of white matter of the genu and splenium of the
      corpus callosum and of the centrum semiovale in 12 detoxified alcoholic women and
      18 control women. Additional analyses examined sex differences in FA and C in
      alcoholic women compared with alcoholic men. Despite absence of group differences
      in regional areas of callosal macrostructure, the alcoholic women had lower FA
      and C in genu and centrum semiovale than the control group of women. These
      measures also correlated with total lifetime consumption of alcohol and
      performance on a test of visual search in the alcoholic women. Sex comparisons
      revealed similar extents of FA abnormality in the genu and centrum semiovale in
      alcoholic men and women and differential effects in other DTI measures, with
      abnormalities present in splenium FA and C in the men and abnormalities present
      in centrum C in the women. These results provide in vivo evidence for disruption
      of white matter microstructure in alcoholic women not necessarily detectable with
      coarser measures of white matter mass and perhaps antedating its appearance.

PMID- 11848715
TI  - An investigation of the value of spin-echo-based fMRI using a Stroop color-word
      matching task and EPI at 3 T.
AB  - This study examines the value of spin-echo-based fMRI for cognitive studies at
      the main magnetic field strength of 3 T using a spin-echo EPI (SE-EPI) sequence
      and a Stroop color-word matching task. SE-EPI has the potential advantage over
      conventional gradient-echo EPI (GE-EPI) that signal losses caused by dephasing
      through the slice are not present, and hence although image distortion will be
      the same as for an equivalent GE-EPI sequence, signal voids will be eliminated.
      The functional contrast in SE-EPI will be lower than for GE-EPI, as static
      dephasing effects do not contribute. As an auxiliary experiment interleaved
      diffusion-weighted and non-diffusion-weighted SE-EPI was performed in the visual
      cortex to further elucidate the mechanims of functional contrast. In the Stroop
      experiment activation was detected in all areas previously found using GE-EPI.
      Additional frontopolar and ventral frontomedian activations were also found,
      which could not be detected using GE-EPI. The experiments from visual cortex
      indicated that at 3 T the BOLD signal change has contributions from the
      extravascular space and larger blood vessels in roughly equal amounts. In
      comparison with GE-EPI the absence of static dephasing effects would seem to
      result in a superior intrinsic spatial resolution. In conclusion the sensitivity
      of SE-EPI at 3 T is sufficient to make it the method of choice for fMR studies
      that require a high degree of spatial localization or where the requirement is to
      detect activation in regions affected by strong susceptibility gradients.

PMID- 11848716
TI  - Brain activity during simulated deception: an event-related functional magnetic
      resonance study.
AB  - TheGuilty Knowledge Test (GKT) has been used extensively to model deception. An
      association between the brain evoked response potentials and lying on the GKT
      suggests that deception may be associated with changes in other measures of brain
      activity such as regional blood flow that could be anatomically localized with
      event-related functional magnetic resonance imaging (fMRI). Blood oxygenation
      level-dependent fMRI contrasts between deceptive and truthful responses were
      measured with a 4 Tesla scanner in 18 participants performing the GKT and
      analyzed using statistical parametric mapping. Increased activity in the anterior
      cingulate cortex (ACC), the superior frontal gyrus (SFG), and the left premotor,
      motor, and anterior parietal cortex was specifically associated with deceptive
      responses. The results indicate that: (a) cognitive differences between deception
      and truth have neural correlates detectable by fMRI, (b) inhibition of the
      truthful response may be a basic component of intentional deception, and (c) ACC
      and SFG are components of the basic neural circuitry for deception.

PMID- 11848717
TI  - Multiple parallel memory systems in the brain of the rat.
AB  - A theory of multiple parallel memory systems in the brain of the rat is
      described. Each system consists of a series of interconnected neural structures.
      The "central structures" of the three systems described are the hippocampus, the
      matrix compartment of the dorsal striatum (caudate-putamen), and the amygdala.
      Information, coded as neural signals, flows independently through each system.
      All systems have access to the same information from situations in which learning
      occurs, but each system is specialized to represent a different kind of
      relationship among the elements (stimulus events, responses, reinforcers) of the
      information that flows through it. The speed and accuracy with which a system
      forms a coherent representation of a learning situation depend on the
      correspondence between the specialization of the system and the relationship
      among the elements of the situation. The coherence of these stored
      representations determines the degree of control exerted by each system on
      behavior in the situation. Although they process information independently the
      systems interact in at least two ways: by simultaneous parallel influence on
      behavioral output and by directly influencing each other. These interactions can
      be cooperative (leading to similar behaviors) or competitive (leading to
      different behaviors). Experimental findings consistent with these ideas, mostly
      from experiments with rats, are reviewed.

PMID- 11848718
TI  - Amino acid release from the intermediate medial hyperstriatum ventrale (IMHV) of
      day-old chicks following a one-trial passive avoidance task.
AB  - Indirect evidence has implicated glutamate and gamma-amino butyric acid in memory
      formation for one-trial passive avoidance learning. We have further examined this
      by following the time course of glutamate and gamma-amino butyric acid release
      from slices prepared from the intermediate medial hyperstriatum ventrale of day
      old chicks (Ross 1 Chunky) trained to avoid a bead covered in the aversant
      methylanthranilate. At various times after training, slices of left and right
      intermediate medial hyperstriatum ventrale were incubated in medium containing 50
      mM potassium chloride and amino acid release was determined. Thirty minutes after
      training there was a bilateral increase in calcium-dependent glutamate release in
      slices from methylanthranilate-trained chicks compared to those trained to peck
      water. This increase was sustained until 1 h in the left hyperstriatum when an
      increase in calcium-dependent gamma-amino butyric acid release was also apparent.
      Glutamate uptake was also enhanced in left hyperstriatum (30 and 60 min) and in
      the right at 30 min. In the right intermediate medial hyperstriatum ventrale of
      methylanthranilate birds glutamate release was increased from 3 to 6.5 h and
      gamma-amino butyric acid at 6.5 h: a time that corresponded to the mobilization
      of a late process required if long-term memory was to be formed. These results
      confirm that the amino acids glutamate and gamma-amino butyric acid are released
      from the intermediate hyperstriatum ventrale in a calcium-dependent,
      neurotransmitter-like manner. Furthermore, changes in the release of these two
      amino acids accompany memory formation for a one-trial learning task in the day
      old chick.

PMID- 11848719
TI  - Effects of posttraining treatments in the posterior cingulate cortex on short-
      and long-term memory for inhibitory avoidance in rats.
AB  - Adult male Wistar rats were bilaterally implanted with indwelling cannulae in the
      caudal region of the posterior cingulate cortex. After recovery, animals were
      trained in a step-down inhibitory avoidance task (3.0-s, 0.4-mA foot shock) and
      received, right after training, a 0.5-microl infusion of vehicle (phosphate
      buffered saline, pH 7.4), of the GABA(A) receptor agonist muscimol (0.1 or 0.5
      microg), of the cAMP-dependent protein kinase (PKA) stimulant Sp-cAMPS (0.1 or
      0.5 microg), or of the PKA inhibitor Rp-cAMPS (0.1 or 0.5 microg). Animals were
      tested twice, 1.5 h and, again, 24 h after training, in order to examine the
      effects of these agents on short- and long-term memory, respectively. Muscimol
      (0.5 but not 0.1 microg) hindered retention for both short- and long-term memory
      (p <.05). Rp-cAMPS (0.1 or 0.5 microg) hindered retention for short-term memory
      (p <.05). In addition, these animals showed lower, but not significantly lower,
      latencies than controls in the test session for long-term memory (p >.10). A
      trend toward an amnesic effect on long-term memory was also observed after Sp
      cAMPS infusion at 0.1 microg (p <.10). These results show that strong stimulation
      of GABAergic synapses in the caudal region of the rat posterior cingulate cortex
      right after training impairs short- and long-term memory (the latter less
      dramatically). The same occurs by inhibiting PKA activity with regard to STM and
      possibly to LTM.

PMID- 11848720
TI  - Transverse patterning reveals a dissociation of simple and configural association
      learning abilities in rats with 192 IgG-saporin lesions of the nucleus basalis
      magnocellularis.
AB  - This experiment tests the hypothesis that the cholinergic nucleus basalis
      magnocellularis (NBM) is necessary for complex or configural association
      learning, but not elemental or simple association learning. Male Long-Evans rats
      with bilateral 192 IgG-saporin lesions of the NBM (n = 12) and sham-operated
      controls (n = 8) were tested in the transverse patterning problem, which provides
      a test of both simple and configural association learning. Rats were trained in
      phases to concurrently solve first one, then two, and finally three different
      visual discriminations; Problem 1 (A+ vs B- sign) and Problem 2 (B+ vs C-) could
      be solved using simple associations, whereas solving Problem 3 (C+ vs A-)
      required the ability to form configural associations. Consistent with our
      hypothesis, the NBM lesion group solved the simple discriminations in Problems 1
      and 2 but showed impaired configural association learning in Problem 3.
      Additionally, when Problem 2 was introduced, previously high levels of
      performance on Problem 1 suffered more in the NBM lesion group than in the
      control group; this finding suggests an impairment in the ability of animals with
      NBM lesions to divide attention among multiple stimuli or to shift between
      strategies for solving different problems. Results support our argument that the
      NBM is critically involved in the acquisition of associative problems requiring a
      configural solution but not in problems that can be solved using only simple
      associations. The observed impairments in configural association learning and the
      apparent loss of cognitive flexibility or capacity are interpreted as reflecting
      specific attentional impairments resulting from NBM damage.

PMID- 11848721
TI  - Two critical periods for cAMP-dependent protein kinase activity during long-term
      memory consolidation in the crab Chasmagnathus.
AB  - Activation of the cAMP pathway was found to be implicated in the memory process.
      In the context-signal learning paradigm of the crab Chasmagnathus, the protein
      kinase (PKA) activator Sp-5,6-DCl-cBIMPS facilitated long-term memory (LTM)
      induced by spaced training while the PKA inhibitor 8-chloroadenosine-3', 5'
      monophosphorothioate, Rp-isomer (Rp-8-Cl-cAMPS) produced amnesia. In the present
      report the effect of the PKA inhibitor on long-term retention was assessed when
      administered (systemic injection of 2 microg/animal) at various times after
      training. According to previous results obtained with a lower dose, retention is
      impaired when the drug is administered immediately pretraining. An effect on
      acquisition was ruled out considering that the drug did not affect the
      performance during training. On the contrary, no effect of the PKA inhibitor was
      found with an immediately posttraining injection and amnesia was observed only
      when training was shortened from 15 to 12 trials (training duration from 45 to 36
      min). At 2 and 12 h posttraining Rp-8-Cl-cAMPS injection failed to impair
      retention, but amnesia was found when the drug was injected at 4 and 8 h after
      training. In order to assess a possible effect of the drug in retrieval, the PKA
      inhibitor was administered 15 min before testing, and no amnestic effect was
      observed. These results suggest that two phases of PKA activity are required
      during consolidation of LTM, one during training and the other between 4 and 8 h
      after training. The link between these two periods of PKA activation and the two
      phases of the transcription factor NF-kappaB activation previously found in this
      model, as well as the similar time course found in rodents, is discussed. An
      amnestic effect of the drug was not found when administered immediately before a
      massed training protocol that yielded an intermediate-term memory, suggesting
      that in this type of memory PKA activation is not required.

PMID- 11848722
TI  - Conditioned memory modulation, freezing, and avoidance as measures of amygdala
      mediated conditioned fear.
AB  - Three conditioned aversive responses were used to infer the existence of an
      unobservable central state of "conditioned fear," and the roles of certain
      amygdala subregions in producing these responses were investigated. Rats received
      tone-shock pairings in one compartment of a shuttle box and no tones or shocks in
      the other, distinctive, compartment. They were then trained to find food in one
      arm of a Y-maze. After the final training trial they were exposed to different
      sets of stimuli in the shuttle box with no shock. Twenty-four hours later rats
      that had received immediate posttraining exposure to the conditioned stimuli (in
      the shock-paired compartment) made significantly more correct responses on the Y
      maze than rats that had been exposed to the neutral stimuli (in the no-shock
      compartment) or rats that had received delayed posttraining exposure to the
      conditioned stimuli. This constitutes a demonstration of posttraining memory
      modulation by conditioned aversive stimuli. Freezing increased during
      posttraining exposure to the conditioned stimuli compared to the neutral stimuli.
      When subsequently allowed to move freely between the two compartments, the rats
      in all groups also showed significant conditioned avoidance of the compartment
      containing the conditioned stimuli. In a second experiment the effects of lesions
      confined to specific parts of the amygdala on the three conditioned responses
      (memory modulation, freezing, avoidance) were tested. Lesions of the central
      nucleus impaired all three conditioned responses; lesions of the medial nucleus
      impaired conditioned modulation and avoidance. These lesions had no effect on
      freezing during the training trials. Lesions of the lateral and basolateral
      nuclei attenuated freezing during both training and testing. The findings suggest
      that the central and medial nuclei of the amygdala may be important parts of
      neural circuits mediating conditioned responses that constitute conditioned
      aversive states, but that conditioned freezing may be mediated independently.

PMID- 11848723
TI  - Surveillance for second primary colorectal cancer after adjuvant chemotherapy: an
      analysis of Intergroup 0089.
AB  - BACKGROUND: The incidence of second primary colorectal cancer in patients with a
      history of colon cancer, compared with patients with a history of adenomatous
      polyps, is unknown. It is unclear whether guidelines for colonoscopy screening in
      patients with polyps are appropriate for patients with previous colon cancer.
      OBJECTIVE: To determine the incidence of second primary colorectal cancer after
      treatment for localized colon cancer and to compare this incidence with that of
      first primary colorectal cancer in both the general population and high-risk
      patients. DESIGN: Historical cohort study. SETTING: An international, multi
      institutional trial of adjuvant 5-fluorouracil-based chemotherapy for localized
      colon cancer. PATIENTS: 3278 patients with resected stage II and stage III colon
      cancer. MEASUREMENTS: Occurrence of endoscopic or radiologic colon surveillance
      and incidence of second primary colorectal cancer. RESULTS: Forty-two cases of
      second primary invasive colon cancer were found over 15 345 person-years of
      follow-up, yielding an incidence rate of 274 per 100 000 person-years (95% CI,
      196 to 369 per 100 000 person-years) and a cumulative incidence of 1.5% (CI, 1.1%
      to 2.0%) at 5 years. This rate was compared with rates of first colon cancer in
      two reference groups: the general population and patients who had undergone
      frequent colonoscopy and polypectomy because of a history of adenomatous polyps;
      standardized incidence ratios were 1.6 (CI, 1.2 to 2.2) and 6.8 (CI, 2.7 to
      22.0), respectively. CONCLUSION: The incidence of second primary colorectal
      cancer remains high despite intensive surveillance strategies.

PMID- 11848724
TI  - Change in lung function and morbidity from chronic obstructive pulmonary disease
      in alpha1-antitrypsin MZ heterozygotes: A longitudinal study of the general
      population.
AB  - BACKGROUND: A deteriorating effect of severe alpha(1)-antitrypsin deficiency (ZZ
      genotype) on lung function is well known, whereas the role of intermediate
      deficiency (MZ genotype) remains uncertain. OBJECTIVE: To test the hypothesis
      that MZ intermediate alpha(1)-antitrypsin deficiency affects pulmonary function
      and disease. DESIGN: Population-based cohort study with 21-year follow-up.
      SETTING: Copenhagen, Denmark. PARTICIPANTS: 9187 adults randomly selected from
      the Danish general population. MEASUREMENTS: Plasma alpha(1)-antitrypsin levels,
      annual decrease in FEV(1), airway obstruction, and hospitalization and mortality
      from chronic obstructive pulmonary disease (COPD). RESULTS: 451 participants
      (4.9%) carried the MZ genotype. Plasma alpha(1)-antitrypsin levels were 31% lower
      in MZ heterozygotes than in persons with the MM genotype (Student t -test, P <
      0.001). Annual decrease in FEV(1) was 25 mL in MZ heterozygotes and 21 mL in
      persons with the MM genotype (t -test, P = 0.048). Airway obstruction was found
      in 19% of MZ heterozygotes compared with 15% of MM carriers (chi-square test, P =
      0.023); in a logistic regression analysis adjusted for age, sex, and tobacco
      consumption, the corresponding odds ratio was 1.3 (CI, 1.0 to 1.7). The incidence
      of hospitalization and mortality from COPD was 32 cases per 10 000 person-years
      in persons with the MZ genotype and 22 cases per 10 000 person-years in those
      with the MM genotype (log-rank test, P = 0.063). In a Cox regression model
      adjusted for age, sex, tobacco use, and FEV(1) at study entry, relative risk for
      COPD outcomes in persons with the MZ genotype versus persons with the MM genotype
      was 1.5 (CI, 1.0 to 2.3). All these results were independent of the S and E
      alleles in this gene and were not affected by cystic fibrosis Delta F508
      heterozygosity. CONCLUSIONS: MZ heterozygotes had a slightly greater rate of
      decrease in FEV(1) and were modestly over-represented among persons with airway
      obstruction and COPD. In the population at large, MZ heterozygosity may account
      for a fraction of COPD cases---on the order of 2%, similar to the percentage of
      persons with COPD who have the severe but rare ZZ genotype.

PMID- 11848725
TI  - The stool antigen test for detection of Helicobacter pylori after eradication
      therapy.
AB  - BACKGROUND: Current noninvasive tests to confirm the eradication of Helicobacter
      pylori must be performed 4 weeks or more after eradication therapy is completed.
      OBJECTIVE: To determine whether the stool antigen test, a relatively new
      noninvasive test for H. pylori, administered at various times after eradication
      therapy correctly identifies persons with persistent H. pylori infection. DESIGN:
      Prospective blinded study. SETTING: Six clinical centers in the United States and
      Europe. PATIENTS: 84 H. pylori --infected patients undergoing endoscopy for upper
      abdominal symptoms. MEASUREMENTS: At baseline and on day 35 after the completion
      of triple eradication therapy, all patients underwent endoscopy with histologic
      examination, rapid urease test and culture, urea breath test, and a stool antigen
      test. The stool antigen test was also performed on days 3, 7, 15, 21, 28, and 35
      after completion of therapy. RESULTS: Compared with the gold-standard endoscopic
      tests on day 35 after antimicrobial therapy, the urea breath test had a
      sensitivity of 94% (95% CI, 71% to 100%) and a specificity of 100% (CI, 94% to
      100%). The stool antigen test had a sensitivity of 94% (CI, 71% to 100%) and a
      specificity of 97% (CI, 89% to 100%). On day 7 after treatment, the stool antigen
      test was predictive of eradication (positive predictive value, 100% [CI, 69% to
      100%]; negative predictive value, 91% [CI, 82% to 97%]). CONCLUSION: A positive
      result on the stool antigen test 7 days after completion of therapy identifies
      patients in whom eradication of H. pylori was unsuccessful.

PMID- 11848726
TI  - Surprisingly small effect of antiviral treatment in patients with hepatitis C.
AB  - BACKGROUND: The effect and applicability of interferon-based antiviral therapies
      in the general population of persons with hepatitis C virus (HCV) infection are
      unknown. OBJECTIVE: To determine the applicability and usefulness of anti-viral
      therapy in a metropolitan clinic population. DESIGN: Retrospective case series of
      consecutively referred patients. SETTING: A teaching county hospital in
      Cleveland, Ohio. PATIENTS: 327 patients referred to a liver clinic after a
      positive result for antibody against HCV on enzyme-linked immunosorbent assay
      (ELISA). MEASUREMENTS: Treatment rates; reasons for nontreatment. RESULTS: 34
      patients had no detectable HCV RNA. Of the remaining 293 patients, 72% were not
      treated for the following reasons: 37% did not adhere to evaluation procedures,
      34% had medical or psychiatric contraindications, 13% had ongoing substance or
      alcohol abuse, 11% preferred no treatment, and 5% had normal liver enzyme levels.
      Only 83 patients (28%) were treated; 13% had a sustained viral response.
      CONCLUSION: Most patients with HCV infection are not candidates for interferon
      based therapies; alternative interventions should be sought for these patients.

PMID- 11848727
TI  - Update in psychiatry.

PMID- 11848728
TI  - A current perspective of suicide and attempted suicide.
AB  - Suicide and suicide attempts are a major cause of death and morbidity worldwide.
      Suicide is generally a complication of a psychiatric disorder, but it requires
      additional risk factors because most psychiatric patients never attempt suicide.
      This review includes a hypothesized stress-diathesis model, which has
      implications for detection of high-risk patients and treatment interventions, and
      discusses promising treatment approaches that have been recently identified.

PMID- 11848729
TI  - Legal, financial, and public health consequences of HIV contamination of blood
      and blood products in the 1980s and 1990s.
AB  - Ensuring the safety of the blood supply connects politics and science. The
      business and service sectors share responsibility for the collection and
      processing of blood donations, and government agencies perform regulatory and
      surveillance roles. The onset of the AIDS epidemic has challenged the interface
      among these systems, leading to widespread fears about compromised safety of the
      blood supply. Because of public concern about blood-supply decisions made in the
      1980s, developed countries in the 1990s established reimbursement programs for
      persons with transfusion-acquired viral infections from blood or blood products,
      adopted diagnostic tests and procedures that improved the safety of the blood
      supply, and held criminal judicial investigations of government officials and
      industry leaders accused of delaying implementation of potential blood-safety
      measures. In contrast, developing countries continue to struggle with blood
      supply safety issues. This paper summarizes the current status of these safety
      concerns in developed countries, where viral transmission from contaminated blood
      or blood products is extremely rare, and in developing countries, where up to 10%
      of HIV infections result from transfusion of blood or blood products.

PMID- 11848730
TI  - NIH conference. Future directions in the study and management of congenital
      adrenal hyperplasia due to 21-hydroxylase deficiency.
AB  - Congenital adrenal hyperplasia describes a group of inherited autosomal recessive
      disorders characterized by an enzymatic defect in cortisol biosynthesis,
      compensatory increases in corticotropin secretion, and adrenocortical
      hyperplasia. 21-Hydroxylase deficiency is responsible for more than 95% of cases
      and is one of the most common known autosomal recessive disorders. The classic or
      severe type presents in the newborn period or early childhood with virilization
      and adrenal insufficiency, with or without salt loss; the mild or nonclassic form
      presents in late childhood or early adulthood with mild hyperandrogenism and is
      an important cause of masculinization and infertility in women. This wide range
      of phenotypic expression is mostly explained by genetic variation, although
      genotype-phenotype discrepancies have been described. Reproductive, metabolic,
      and other comorbid conditions, including risk for tumors, are currently under
      investigation in both forms of the disease. A high proportion of patients with
      adrenal incidentalomas may be homozygous or heterozygous for 21-hydroxylase
      deficiency. Women with congenital adrenal hyperplasia often develop the
      polycystic ovary syndrome. Ectopic adrenal rest tissue is often found in the
      testes of men with congenital adrenal hyperplasia; characteristic clinical and
      radiologic findings help differentiate this tissue from other tumors. Levels of
      corticotropin-releasing hormone are elevated in patients with depression and
      anxiety and are expected to be elevated in patients with congenital adrenal
      hyperplasia; it is unknown whether patients with 21-hydroxylase deficiency have
      an increased incidence of these psychiatric disorders. Abnormalities in both the
      structure and function of the adrenal medulla have been shown in patients with
      classic congenital adrenal hyperplasia, and the degree of adrenomedullary
      impairment may be a biomarker of disease severity. The 21-hydroxylase-deficient
      mouse has provided a useful model with which to examine disease mechanisms and
      test new therapeutic interventions in classic disease, including gene therapy.
      Treatment of this condition is intended to reduce excessive corticotropin
      secretion and replace both glucocorticoids and mineralocorticoids. However,
      clinical management is often complicated by inadequately treated
      hyperandrogenism, iatrogenic hypercortisolism, or both. New treatment approaches
      currently under investigation include combination therapy to block androgen
      action and inhibit estrogen production, and bilateral adrenalectomy in the most
      severely affected patients. Other approaches, which are in a preclinical stage of
      investigation, include treatment with a corticotropin-releasing hormone
      antagonist and gene therapy.

PMID- 11848731
TI  - Second primary colorectal cancer: the consequence of management failure at
      several potential levels.

PMID- 11848732
TI  - Influenza: prospects for control.

PMID- 11848734
TI  - Quinine-induced blindness reversed by an increase in alpha1-acid glycoprotein
      level.

PMID- 11848737
TI  - Summaries for patients. Second colorectal cancer in patients who had first colon
      cancer treated with surgery and chemotherapy.

PMID- 11848738
TI  - Summaries for patients. Lung function and death from chronic obstructive
      pulmonary disease in alpha1-antitrypsin MZ heterozygotes.

PMID- 11848740
TI  - Summaries for patients. Who gets antiviral treatment for hepatitis C?

PMID- 11848739
TI  - Summaries for patients. Detection of persistent Helicobacter pylori infection.

PMID- 11848741
TI  - Introduction: Frontiers in Organic Synthesis.

PMID- 11848742
TI  - Design Constraints in Practical Syntheses of Complex Molecules: Current Status,
      Case Studies with Carbohydrates and Alkaloids, and Future Perspectives.

PMID- 11848743
TI  - Chiral Allylic and Allenic Stannanes as Reagents for Asymmetric Synthesis.

PMID- 11848744
TI  - Transition Metal-Mediated Cycloaddition Reactions.

PMID- 11848746
TI  - Domino Reactions in Organic Synthesis.

PMID- 11848745
TI  - Diyl Trapping and Electroreductive Cyclization Reactions.

PMID- 11848747
TI  - Tandem [4+2]/[3+2] Cycloadditions of Nitroalkenes.

PMID- 11848748
TI  - Tandem Dielsminus signAlder Cycloadditions in Organic Synthesis.

PMID- 11848749
TI  - Tandem Radical Reactions of Carbon Monoxide, Isonitriles, and Other Reagent
      Equivalents of the Geminal Radical Acceptor/Radical Precursor Synthon.

PMID- 11848750
TI  - Tandem Reactions in Organic Synthesis: Novel Strategies for Natural Product
      Elaboration and the Development of New Synthetic Methodology.

PMID- 11848751
TI  - Cascade Radical Cyclizations via Biradicals Generated from Enediynes, Enyne
      Allenes, and Enyne-Ketenes.

PMID- 11848752
TI  - Cascade Processes of Metallo Carbenoids.

PMID- 11848753
TI  - Carbeneminus signAlkyneminus signAlkene Cyclization Reactions.

PMID- 11848754
TI  - Selective Preparation of Complex Polycyclic Molecules from Acyclic Precursors via
      Radical Mediated- or Transition Metal-Catalyzed Cascade Reactions.

PMID- 11848755
TI  - Sequencing Reactions with Samarium(II) Iodide.

PMID- 11848756
TI  - Manganese(III)-Based Oxidative Free-Radical Cyclizations.

PMID- 11848757
TI  - Cyclic Carbopalladation. A Versatile Synthetic Methodology for the Construction
      of Cyclic Organic Compounds.

PMID- 11848759
TI  - (pi-Allyl)tricarbonyliron Lactone Complexes in Organic Synthesis: A Useful and
      Conceptually Unusual Route to Lactones and Lactams.

PMID- 11848758
TI  - Asymmetric Transition Metal-Catalyzed Allylic Alkylations.

PMID- 11848760
TI  - Recent Advances in the Chemoenzymatic Synthesis of Carbohydrates and Carbohydrate
      Mimetics.

PMID- 11848761
TI  - Ellagitannin Chemistry.

PMID- 11848763
TI  - Research at the Interface between Chemistry and Virology: Development of a
      Molecular Flashlight.

PMID- 11848762
TI  - Total Syntheses of Pumiliotoxin A and Allopumiliotoxin Alkaloids. Interplay of
      Pharmacologically Active Natural Products and New Synthetic Methods and
      Strategies.

PMID- 11848765
TI  - Synthesis and Applications of Small Molecule Libraries.

PMID- 11848764
TI  - Conjugated Macromolecules of Precise Length and Constitution. Organic Synthesis
      for the Construction of Nanoarchitectures.

PMID- 11848766
TI  - Antifreeze Proteins: Structures and Mechanisms of Function.

PMID- 11848767
TI  - The Effects of DNA Covalent Adducts on in Vitro Transcription.

PMID- 11848768
TI  - Transition Metal-Catalyzed Carbocyclizations in Organic Synthesis.

PMID- 11848769
TI  - Palladium-Catalyzed Alternating Copolymerization of Alkenes and Carbon Monoxide.

PMID- 11848770
TI  - Glycobiology: Toward Understanding the Function of Sugars.

PMID- 11848771
TI  - Artificial Enzymes.

PMID- 11848772
TI  - Luminescent and Redox-Active Polynuclear Transition Metal Complexes.

PMID- 11848773
TI  - 1,2-Amino Alcohols and Their Heterocyclic Derivatives as Chiral Auxiliaries in
      Asymmetric Synthesis.

PMID- 11848774
TI  - Chemical Redox Agents for Organometallic Chemistry.

PMID- 11848775
TI  - Resonance Raman Intensities and Charge-Transfer Reorganization Energies.

PMID- 11848776
TI  - Comparison of Phosphorus and Silicon: Hypervalency, Stereochemistry, and
      Reactivity.

PMID- 11848777
TI  - Organic Carbonates.

PMID- 11848778
TI  - Preparation and Spectroscopic Investigations of Mixed Octahedral Complexes and
      Clusters.

PMID- 11848779
TI  - Quantum-Chemical Descriptors in QSAR/QSPR Studies.

PMID- 11848780
TI  - Comparative QSAR: Toward a Deeper Understanding of Chemicobiological
      Interactions.

PMID- 11848781
TI  - New Bonding Modes, Fluxional Behavior, and Reactivity in Dinuclear Complexes
      Bridged by Four-Electron Donor Unsaturated Hydrocarbons.

PMID- 11848782
TI  - Review of the Defensive Chemistry of Coccinellids.

PMID- 11848783
TI  - Organic Polyvalent Iodine Compounds.

PMID- 11848784
TI  - Chemistry of 7-Azabicyclo[2.2.1]hepta-2,5-dienes, 7-Azabicyclo[2.2.1]hept-2-enes,
      and 7-Azabicyclo[2.2.1]heptanes.

PMID- 11848785
TI  - Modern Methods of Monosaccharide Synthesis from Non-Carbohydrate Sources.

PMID- 11848786
TI  - Surface Chemistry-Advances and Technological Impact 1996.

PMID- 11848787
TI  - Modern Surface Science and Surface Technologies: An Introduction.

PMID- 11848788
TI  - Semiconductor Surface Reconstruction: The Structural Chemistry of Two-Dimensional
      Surface Compounds.

PMID- 11848789
TI  - Atomically-Resolved Studies of the Chemistry and Bonding at Silicon Surfaces.

PMID- 11848790
TI  - Reconstruction of Clean and Adsorbate-Covered Metal Surfaces.

PMID- 11848791
TI  - High-Resolution Helium Atom Time-of-Flight Spectroscopy of Low-Frequency
      Vibrations of Adsorbates.

PMID- 11848792
TI  - Modeling of Surface Processes as Exemplified by Hydrocarbon Reactions.

PMID- 11848793
TI  - Liquid Interfaces Probed by Second-Harmonic and Sum-Frequency Spectroscopy.

PMID- 11848794
TI  - Mimicking Aspects of Heterogeneous Catalysis: Generating, Isolating, and Reacting
      Proposed Surface Intermediates on Single Crystals in Vacuum.

PMID- 11848795
TI  - Probing Surface Reaction Mechanisms Using Chemical and Vibrational Methods: Alkyl
      Oxidation and Reactivity of Alcohols on Transitions Metal Surfaces.

PMID- 11848796
TI  - Organic Reactions at Well-Defined Oxide Surfaces.

PMID- 11848797
TI  - Surface Structure and Reactivity: Reactions on Face-Centered Cubic (110) Metal
      Surfaces Involving Adatom-Induced Reconstructions.

PMID- 11848798
TI  - Chemical Reactions and Solvation at Liquid Interfaces: A Microscopic Perspective.

PMID- 11848799
TI  - Carbide and Nitride Overlayers on Early Transition Metal Surfaces: Preparation,
      Characterization, and Reactivities.

PMID- 11848800
TI  - Role of Surface Chemistry in Semiconductor Thin Film Processing.

PMID- 11848802
TI  - Formation and Structure of Self-Assembled Monolayers.

PMID- 11848801
TI  - Surface Chemistry in the Chemical Vapor Deposition of Electronic Materials.

PMID- 11848803
TI  - Introduction: Fluorine Chemistry.

PMID- 11848805
TI  - Fluorinated Carbenes.

PMID- 11848804
TI  - Structure, Reactivity, and Chemistry of Fluoroalkyl Radicals.

PMID- 11848806
TI  - Fluorinated Carbanions.

PMID- 11848807
TI  - Fluorinated Ylides and Related Compounds.

PMID- 11848809
TI  - Electrophilic NF Fluorinating Agents.

PMID- 11848808
TI  - Selective Fluorinations by Reagents Containing the OF Group.

PMID- 11848810
TI  - Electrophilic Perfluoroalkylating Agents.

PMID- 11848811
TI  - Fluorinated Peroxides.

PMID- 11848812
TI  - Polyfluorinated Oxaziridines: Synthesis and Reactivity.

PMID- 11848813
TI  - Enantiospecific Synthesis of Heterocycles from alpha-Amino Acids.

PMID- 11848814
TI  - Stable Ion Studies of Protonation and Oxidation of Polycyclic Arenes(,).

PMID- 11848815
TI  - Oxidation of B, BH, BH(2), and B(m)()H(n)() Species: Thermochemistry and
      Kinetics.

PMID- 11848816
TI  - Neutral Six-Coordinate Phosphorus.

PMID- 11848817
TI  - Photophysics and Mechanisms of Intramolecular Electronic Energy Transfer in
      Bichromophoric Molecular Systems: Solution and Supersonic Jet Studies.

PMID- 11848818
TI  - Electronic Structure and Properties of the Transactinides and Their Compounds.

PMID- 11848819
TI  - Hydrido Complexes of Palladium.

PMID- 11848820
TI  - A Review of the Selective Catalytic Reduction of Aromatic Nitro Compounds into
      Aromatic Amines, Isocyanates, Carbamates, and Ureas Using CO.

PMID- 11848821
TI  - Group V and VI Alkali Nitridometalates: A Growing Class of Compounds with
      Structures Related to Silicate Chemistry.

PMID- 11848822
TI  - The Organometallic Chemistry of Carbon Dioxide.

PMID- 11848823
TI  - In/Out Isomerism.

PMID- 11848824
TI  - New Developments in Matrix Isolation Spectroscopy.

PMID- 11848825
TI  - Open-Shell Organometallics as a Bridge between Werner-Type and Low-Valent
      Organometallic Complexes. The Effect of the Spin State on the Stability,
      Reactivity, and Structure.

PMID- 11848826
TI  - Hetero- and Metallasiloxanes Derived from Silanediols, Disilanols, Silanetriols,
      and Trisilanols.

PMID- 11848827
TI  - Preface: Bioinorganic Enzymology.

PMID- 11848828
TI  - Structural and Functional Aspects of Metal Sites in Biology.

PMID- 11848829
TI  - Ironminus signSulfur Proteins with Nonredox Functions.

PMID- 11848830
TI  - Aconitase as Ironminus signSulfur Protein, Enzyme, and Iron-Regulatory Protein.

PMID- 11848831
TI  - Recent Advances in Zinc Enzymology.

PMID- 11848832
TI  - Binuclear Metallohydrolases.

PMID- 11848833
TI  - Theory and Practice of Electron Transfer within Proteinminus signProtein
      Complexes: Application to the Multidomain Binding of Cytochrome c by Cytochrome c
      Peroxidase.

PMID- 11848834
TI  - Protein Control of Redox Potentials of Ironminus signSulfur Proteins.

PMID- 11848836
TI  - Mechanisms Whereby Mononuclear Copper Proteins Functionalize Organic Substrates.

PMID- 11848835
TI  - Nickel-Containing Carbon Monoxide Dehydrogenase/Acetyl-CoA Synthase(,).

PMID- 11848837
TI  - Multicopper Oxidases and Oxygenases.

PMID- 11848838
TI  - Dioxygen Activation by Enzymes with Mononuclear Non-Heme Iron Active Sites.

PMID- 11848839
TI  - Dioxygen Activation by Enzymes Containing Binuclear Non-Heme Iron Clusters.

PMID- 11848841
TI  - The Mononuclear Molybdenum Enzymes.

PMID- 11848840
TI  - Pterin-Dependent Amino Acid Hydroxylases.

PMID- 11848842
TI  - Tungstoenzymes.

PMID- 11848843
TI  - Heme-Containing Oxygenases.

PMID- 11848844
TI  - Heme/Copper Terminal Oxidases.

PMID- 11848845
TI  - Manganese Enzymes with Binuclear Active Sites.

PMID- 11848846
TI  - Manganese Cluster in Photosynthesis: Where Plants Oxidize Water to Dioxygen.

PMID- 11848847
TI  - Dissimilatory Nitrite and Nitric Oxide Reductases.

PMID- 11848848
TI  - Structural Basis of Biological Nitrogen Fixation.

PMID- 11848849
TI  - Mechanism of Molybdenum Nitrogenase.

PMID- 11848850
TI  - Structureminus signFunction Relationships of Alternative Nitrogenases.

PMID- 11848851
TI  - Reactions with Molecular Hydrogen in Microorganisms: Evidence for a Purely
      Organic Hydrogenation Catalyst.

PMID- 11848852
TI  - Comparisons of Indefinite Self-Association Models.

PMID- 11848853
TI  - Synthetic Aspects of the Di-pi-methane Rearrangement.

PMID- 11848854
TI  - Giant Hexagonal Bilayer Hemoglobins.

PMID- 11848856
TI  - Bioisosterism: A Rational Approach in Drug Design.

PMID- 11848855
TI  - Transition Metal Alkane Complexes(dagger).

PMID- 11848857
TI  - Electronic Effects in the Electric Double Layer.

PMID- 11848858
TI  - Structureminus signOdor Relationships.

PMID- 11848860
TI  - The Chemistry of Highly Fluorinated Carbocations.

PMID- 11848859
TI  - Synthesis and Reactivity of sp(3)-Geminated Organodimetallics.

PMID- 11848861
TI  - Oxiranyl Anions and Aziridinyl Anions.

PMID- 11848862
TI  - Surface Chemistry and Spectroscopy of Chromium in Inorganic Oxides.

PMID- 11848863
TI  - Synthetic Water-Oxidation Catalysts for Artificial Photosynthetic Water
      Oxidation.

PMID- 11848864
TI  - Cavity Ringdown Laser Absorption Spectroscopy: History, Development, and
      Application to Pulsed Molecular Beams.

PMID- 11848865
TI  - Free-Radical Reactions in the Synthesis of alpha-Amino Acids and Derivatives.

PMID- 11848866
TI  - Chemistry and Processes of Color Photography.

PMID- 11848867
TI  - Cysteine Proteases and Their Inhibitors.

PMID- 11848869
TI  - Electrochemically Active Polymers for Rechargeable Batteries.

PMID- 11848868
TI  - Synthetic Principles for Bandgap Control in Linear pi-Conjugated Systems.

PMID- 11848870
TI  - Dimeric and Oligomeric Steroids.

PMID- 11848871
TI  - EPR as a Tool To Investigate the Transition Metal Chemistry on Oxide Surfaces.

PMID- 11848872
TI  - New Perspectives in the Chemistry and Biochemistry of the Tunichromes and Related
      Compounds.

PMID- 11848874
TI  - Nucleic Acid Selection and the Challenge of Combinatorial Chemistry.

PMID- 11848873
TI  - Introduction: Combinatorial Chemistry.

PMID- 11848875
TI  - In Vitro Selection of Catalytic Polynucleotides.

PMID- 11848876
TI  - Phage Display.

PMID- 11848878
TI  - The Current Status of Heterocyclic Combinatorial Libraries.

PMID- 11848877
TI  - The "One-Bead-One-Compound" Combinatorial Library Method.

PMID- 11848879
TI  - Spatially Addressable Combinatorial Libraries.

PMID- 11848880
TI  - Organic Synthesis on Soluble Polymer Supports: Liquid-Phase Methodologies.

PMID- 11848882
TI  - Metal-Assisted Cycloaddition Reactions in Organotransition Metal Chemistry.

PMID- 11848881
TI  - Three- and Four-Coordinate Gold(I) Complexes.

PMID- 11848883
TI  - Strong Closed-Shell Interactions in Inorganic Chemistry.

PMID- 11848884
TI  - Metalminus signMetal Interactions in Linked Metallocenes.

PMID- 11848885
TI  - Synthesis of Polyquinane Natural Products: An Update.

PMID- 11848886
TI  - Lewis Acid Complexation of Tertiary Amines and Related Compounds: A Strategy for
      alpha-Deprotonation and Stereocontrol.

PMID- 11848887
TI  - The Peroxidaseminus signOxidase Oscillator and Its Constituent Chemistries.

PMID- 11848888
TI  - Perfluoroalkylation with Organosilicon Reagents.

PMID- 11848889
TI  - CC-1065 and the Duocarmycins: Synthetic Studies.

PMID- 11848890
TI  - A Critical Appraisal of the Evolution of N-Nitrosoureas as Anticancer Drugs.

PMID- 11848892
TI  - Biotin: A Timeless Challenge for Total Synthesis.

PMID- 11848891
TI  - Oxidative Addition Reactions of Organoplatinum(II) Complexes with Nitrogen-Donor
      Ligands.

PMID- 11848893
TI  - Ultrathin Organic Films Grown by Organic Molecular Beam Deposition and Related
      Techniques.

PMID- 11848894
TI  - Electron Spectroscopy Using Metastable Atoms as Probes for Solid Surfaces.

PMID- 11848895
TI  - The Activation of Aromatic Molecules with Pentaammineosmium(II).

PMID- 11848896
TI  - Selenium Concentrations in Natural and Environmental Waters.

PMID- 11848898
TI  - Stereochemical Control in Organic Synthesis Using Silicon-Containing Compounds.

PMID- 11848897
TI  - Helicates as Versatile Supramolecular Complexes.

PMID- 11848899
TI  - Synthesis, Structure, and Reactions of Hydride, Borohydride, and Aluminohydride
      Compounds of the f-Elements.

PMID- 11848900
TI  - Chemical Synthesis of Natural Product Peptides: Coupling Methods for the
      Incorporation of Noncoded Amino Acids into Peptides.

PMID- 11848901
TI  - Expanded Porphyrins and Their Heterologs.

PMID- 11848902
TI  - Asymmetric Ylide Reactions: Epoxidation, Cyclopropanation, Aziridination,
      Olefination, and Rearrangement.

PMID- 11848903
TI  - From Microporous to Mesoporous Molecular Sieve Materials and Their Use in
      Catalysis.

PMID- 11848904
TI  - Recent Advances in the Chemistry of Heterocarborane Complexes Incorporating s-
      and p-Block Elements.

PMID- 11848905
TI  - Simplification of Mathematical Models of Chemical Reaction Systems.

PMID- 11848906
TI  - Properties and Synthetic Utility of N-Substituted Benzotriazoles.

PMID- 11848907
TI  - Mechanism of Rubisco: The Carbamate as General Base.

PMID- 11848908
TI  - Hemiporphyrazines as Targets for the Preparation of Molecular Materials:
      Synthesis and Physical Properties.

PMID- 11848909
TI  - Dihydrogen Complexes as Homogeneous Reduction Catalysts.

PMID- 11848910
TI  - Synthesis of Methylene- and Alkylidenecyclopropane Derivatives.

PMID- 11848911
TI  - Lectins: Carbohydrate-Specific Proteins That Mediate Cellular Recognition.

PMID- 11848912
TI  - Metal-Initiated Amination of Alkenes and Alkynes.

PMID- 11848913
TI  - Protein Radicals in Enzyme Catalysis.

PMID- 11848914
TI  - Partially Modified Retro-Inverso Peptides: Development, Synthesis, and
      Conformational Behavior.

PMID- 11848915
TI  - Femtomole Adsorption Calorimetry on Single-Crystal Surfaces.

PMID- 11848916
TI  - Selectinminus signCarbohydrate Interactions: From Natural Ligands to Designed
      Mimics.

PMID- 11848917
TI  - Asymmetric 1,3-Dipolar Cycloaddition Reactions.

PMID- 11848919
TI  - Introduction to RNA/DNA Cleavage.

PMID- 11848918
TI  - Recent Advances in Asymmetric Catalytic Metal Carbene Transformations.

PMID- 11848920
TI  - Inorganic Mimics of Ribonucleases and Ribozymes: From Random Cleavage to Sequence
      Specific Chemistry to Catalytic Antisense Drugs.

PMID- 11848921
TI  - Kinetics and Mechanisms for the Cleavage and Isomerization of the Phosphodiester
      Bonds of RNA by Bronsted Acids and Bases.

PMID- 11848922
TI  - The Hydrolysis of RNA: From Theoretical Calculations to the Hammerhead Ribozyme
      Mediated Cleavage of RNA.

PMID- 11848923
TI  - Mechanisms of Ribozyme-Mediated RNA Cleavage.

PMID- 11848924
TI  - Ribonuclease A.

PMID- 11848925
TI  - Metal Activation of Enzymes in Nucleic Acid Biochemistry.

PMID- 11848926
TI  - Oxidative Strand Scission of Nucleic Acids: Routes Initiated by Hydrogen
      Abstraction from the Sugar Moiety.

PMID- 11848927
TI  - Oxidative Nucleobase Modifications Leading to Strand Scission.

PMID- 11848928
TI  - Cleavage of Nucleic Acids by Bleomycin.

PMID- 11848929
TI  - Photocleavage of Nucleic Acids.

PMID- 11848930
TI  - Photoprocesses of Copper Complexes That Bind to DNA.

PMID- 11848931
TI  - Chemistry of Glycosylases and Endonucleases Involved in Base-Excision Repair.

PMID- 11848932
TI  - Enzymatic Aspects of Isoprenoid Chain Elongation.

PMID- 11848933
TI  - Interactions between Carbocations and Anions in Crystals.

PMID- 11848934
TI  - The Tentacular Chemistry of [CpRu(OMe)](2).

PMID- 11848935
TI  - Time-Resolved Vibrational Spectroscopy of Electronically Excited Inorganic
      Complexes in Solution.

PMID- 11848936
TI  - The Molecular Mechanism of Autoxidation for Myoglobin and Hemoglobin: A Venerable
      Puzzle.

PMID- 11848937
TI  - Crystal Engineering and Organometallic Architecture.

PMID- 11848938
TI  - Additions of Organometallic Reagents to C=N Bonds: Reactivity and Selectivity.

PMID- 11848939
TI  - Medium Effects on Charge Transfer in Metal Complexes.

PMID- 11848940
TI  - The Binary Rare Earth Oxides.

PMID- 11848941
TI  - The Chemistry of Neutron Capture Therapy.

PMID- 11848942
TI  - Site-Specific Thermodynamics: Understanding Cooperativity in Molecular
      Recognition.

PMID- 11848943
TI  - Carrier-Based Ion-Selective Electrodes and Bulk Optodes. 2. Ionophores for
      Potentiometric and Optical Sensors.

PMID- 11848944
TI  - Allylic Amination.

PMID- 11848945
TI  - Chiroptical Properties of the Benzene Chromophore. A Method for the Determination
      of the Absolute Configurations of Benzene Compounds by Application of the Benzene
      Sector and Benzene Chirality Rules.

PMID- 11848946
TI  - Cyclodextrins: Introduction.

PMID- 11848947
TI  - Introduction and General Overview of Cyclodextrin Chemistry.

PMID- 11848948
TI  - NMR Studies of Cyclodextrins and Cyclodextrin Complexes.

PMID- 11848949
TI  - Structures of the Common Cyclodextrins and Their Larger Analogues-Beyond the
      Doughnut.

PMID- 11848950
TI  - Structural Aspects of Stereodifferentiation in the Solid State.

PMID- 11848951
TI  - Applications of Computational Chemistry to the Study of Cyclodextrins.

PMID- 11848952
TI  - Complexation Thermodynamics of Cyclodextrins.

PMID- 11848953
TI  - Synthetic Cyclic Oligosaccharides.

PMID- 11848954
TI  - Cyclodextrin-Based Catenanes and Rotaxanes.

PMID- 11848955
TI  - Methods for Selective Modifications of Cyclodextrins.

PMID- 11848956
TI  - Biomimetic Reactions Catalyzed by Cyclodextrins and Their Derivatives.

PMID- 11848958
TI  - Industrial Applications of Cyclodextrins.

PMID- 11848957
TI  - Organic Reactions Mediated by Cyclodextrins.

PMID- 11848959
TI  - Cyclodextrin Drug Carrier Systems.

PMID- 11848960
TI  - Quantum Mechanical Exchange Coupling in Polyhydride and Dihydrogen Complexes.

PMID- 11848962
TI  - Reactions of Transition Metal Complexes with Fullerenes (C(60), C(70), etc.) and
      Related Materials.

PMID- 11848961
TI  - Abiological Ironminus signSulfur Clusters.

PMID- 11848964
TI  - The Use of Sulfonyl 1,3-Dienes in Organic Synthesis.

PMID- 11848965
TI  - Prediction from Molecular Shape of Solute Orientational Order in Liquid Crystals.

PMID- 11848963
TI  - Activation and Reaction Volumes in Solution. 3.

PMID- 11848966
TI  - The Chemistry of Neutron Capture Therapy. (Chem. Rev. 1998, 98, 1515. Published
      on the Web May 20, 1998).

PMID- 11848967
TI  - Absolute Asymmetric Synthesis under Physical Fields: Facts and Fictions.

PMID- 11848968
TI  - 1,1'-Binaphthyl Dimers, Oligomers, and Polymers: Molecular Recognition,
      Asymmetric Catalysis, and New Materials.

PMID- 11848969
TI  - Thermodynamics of Calixarene Chemistry.

PMID- 11848970
TI  - C(60)-Based Electroactive Organofullerenes.

PMID- 11848971
TI  - Occurrence and Constitution of Natural and Synthetic Ferrihydrite, a Widespread
      Iron Oxyhydroxide.

PMID- 11848972
TI  - Group 4 ansa-Cyclopentadienyl-Amido Catalysts for Olefin Polymerization.

PMID- 11848973
TI  - Ruthenium-Catalyzed Reactions for Organic Synthesis.

PMID- 11848974
TI  - Protein Radicals in Enzyme Catalysis. [Chem. Rev. 1998, 98, 705minus sign762.

PMID- 11848975
TI  - Hyaluronan: Preparation, Structure, Properties, and Applications.

PMID- 11848977
TI  - DNA Cross-Linking Agents as Antitumor Drugs.

PMID- 11848976
TI  - Transition Metalminus signBoryl Compounds: Synthesis, Reactivity, and Structure.

PMID- 11848978
TI  - Transition Metal Complexes Containing Allenylidene, Cumulenylidene, and Related
      Ligands.

PMID- 11848979
TI  - Resorcinolic Lipids, the Natural Non-isoprenoid Phenolic Amphiphiles and Their
      Biological Activity.

PMID- 11848980
TI  - Synthesis of Functionalized Bicyclo[3.2.1]octanes and Their Multiple Uses in
      Organic Chemistry.

PMID- 11848981
TI  - Metal Oxide Surfaces and Their Interactions with Aqueous Solutions and Microbial
      Organisms.

PMID- 11848982
TI  - Reactions of Hydrosilanes with Transition-Metal Complexes: Formation of Stable
      Transition-Metal Silyl Compounds.

PMID- 11848983
TI  - Ab Initio Methods for the Calculation of NMR Shielding and Indirect Spinminus
      signSpin Coupling Constants.

PMID- 11848984
TI  - Supercritical Fluids: Introduction.

PMID- 11848985
TI  - Solvation in Supercritical Fluids: Its Effects on Energy Transfer and Chemical
      Reactions.

PMID- 11848986
TI  - Solvent Density Inhomogeneities in Supercritical Fluids.

PMID- 11848987
TI  - Occurrence of Holes in Ternary Fluid Multiphase Systems of Near-Critical Carbon
      Dioxide and Certain Solutes.

PMID- 11848989
TI  - Supercritical Fluids in Heterogeneous Catalysis.

PMID- 11848988
TI  - Homogeneous Organic Reactions as Mechanistic Probes in Supercritical Fluids.

PMID- 11848990
TI  - Homogeneous Catalysis in Supercritical Fluids.

PMID- 11848991
TI  - New Directions in Inorganic and Metal-Organic Coordination Chemistry in
      Supercritical Fluids.

PMID- 11848992
TI  - Polymerizations in Supercritical Carbon Dioxide.

PMID- 11848993
TI  - Phase Behavior of Polymers in Supercritical Fluid Solvents.

PMID- 11848994
TI  - Organic Chemical Reactions in Supercritical Water.

PMID- 11848995
TI  - Supercritical Biocatalysis.

PMID- 11848996
TI  - Carceplexes and Hemicarceplexes.

PMID- 11848997
TI  - Structurally Diverse pi-Cyclopentadienyl Complexes of the Main Group Elements.

PMID- 11848998
TI  - Carbonminus signCarbon Bond Formations Involving Organochromium(III) Reagents.

PMID- 11848999
TI  - Chemistry of 2-Acylcycloalkane-1,3-diones.

PMID- 11849000
TI  - Molecular Photodynamics in Rare Gas Solids.

PMID- 11849001
TI  - Organometallic Polymers with Transition Metals in the Main Chain.

PMID- 11849003
TI  - Quantum Molecular Dynamics of Ultrafast Processes in Large Polyatomic Systems.

PMID- 11849004
TI  - Photochemistry and Photophysics of Chromium(III) Complexes.

PMID- 11849002
TI  - Carbonminus signCarbon Bond Forming Solid-Phase Reactions.

PMID- 11849005
TI  - Nanostructures: Introduction.

PMID- 11849006
TI  - Interlocked Macromolecules.

PMID- 11849007
TI  - About Dendrimers: Structure, Physical Properties, and Applications.

PMID- 11849008
TI  - Suprasupermolecules with Novel Properties: Metallodendrimers.

PMID- 11849009
TI  - Polyphenylene Nanostructures.

PMID- 11849010
TI  - Nanotubes from Carbon.

PMID- 11849011
TI  - Lithographic Imaging Techniques for the Formation of Nanoscopic Features.

PMID- 11849012
TI  - Unconventional Methods for Fabricating and Patterning Nanostructures.

PMID- 11849013
TI  - Programmed Materials Synthesis with DNA.

PMID- 11849014
TI  - Molecular Rods. 1. Simple Axial Rods.

PMID- 11849015
TI  - Nano-Optics in the Biological World: Beetles, Butterflies, Birds, and Moths.

PMID- 11849017
TI  - Scanning Probe Studies of Single Nanostructures.

PMID- 11849016
TI  - Angle-Dependent Optical Effects Deriving from Submicron Structures of Films and
      Pigments.

PMID- 11849018
TI  - Chemistry of Acyl Radicals.

PMID- 11849019
TI  - Room-Temperature Ionic Liquids. Solvents for Synthesis and Catalysis.

PMID- 11849020
TI  - Generation, Characterization, and Transformations of Unsaturated Carbenium Ions
      in Zeolites.

PMID- 11849021
TI  - Anomalous or Mass-Independent Isotope Effects.

PMID- 11849023
TI  - Implicit Solvation Models: Equilibria, Structure, Spectra, and Dynamics.

PMID- 11849022
TI  - Structural Insight into the Aromatic Amino Acid Hydroxylases and Their Disease
      Related Mutant Forms.

PMID- 11849024
TI  - Oxygen-Avid Hemoglobin of Ascaris.

PMID- 11849025
TI  - Structure and Reactivity of Earlyminus signLate Heterobimetallic Complexes.

PMID- 11849027
TI  - Elementminus signElement Addition to Alkynes Catalyzed by the Group 10 Metals.

PMID- 11849026
TI  - Applications of Radiolabeled Boron Clusters to the Diagnosis and Treatment of
      Cancer.

PMID- 11849028
TI  - pi-Bonding and the Lone Pair Effect in Multiple Bonds between Heavier Main Group
      Elements.

PMID- 11849029
TI  - Kinetics and Mechanisms of Reactions of Thiol, Thiono, and Dithio Analogues of
      Carboxylic Esters with Nucleophiles.

PMID- 11849030
TI  - Comparative Quantitative Structureminus signActivity Relationship Studies on Anti
      HIV Drugs.

PMID- 11849031
TI  - Niobium Compounds: Preparation, Characterization, and Application in
      Heterogeneous Catalysis.

PMID- 11849033
TI  - Cyanohydrins in Nature and the Laboratory: Biology, Preparations, and Synthetic
      Applications.

PMID- 11849032
TI  - Photoluminescence Properties of Multinuclear Copper(I) Compounds.

PMID- 11849034
TI  - In vivo distribution of chromium from chromium picolinate in rats and
      implications for the safety of the dietary supplement.
AB  - Chromium picolinate, [Cr(pic)(3)], is the second most popular nutritional
      supplement after calcium supplements. However, the supplement, unlike simple
      inorganic Cr(III) salts, has been shown in the presence of biological reducing
      agents in vitro to catalytically generate appreciable quantities of hydroxyl
      radicals, resulting in DNA damage. The complex has also been shown to be
      remarkably stable in vitro at neutral, basic, or weakly acidic pHs. Thus, the
      significance of this ability to generate hydroxyl radicals depends on whether the
      complex is absorbed by cells intact along with the stability and concentration of
      the complex in cells. Consequently, male Sprague Dawley rats have been injected
      with (51)Cr- and (3)H-labeled [Cr(pic)(3)]. The tissue distribution, urinary and
      fecal loss, and subcellular hepatocyte distribution and concentration of the
      labels suggest that [Cr(pic)(3)] has a lifetime of less than 1 day in vivo,
      minimizing the potential threat from the supplement itself.

PMID- 11849035
TI  - Fate of indole-3-carbinol in cultured human breast tumor cells.
AB  - Indole-3-carbinol (I3C), a natural component of Brassica vegetables, is a
      promising cancer preventive agent that can reduce the incidence of tumors in
      reproductive organs when administered in the diet. Here we report on the
      metabolic fate of radiolabeled I3C in MCF-7 cells. I3C was surprisingly inert to
      metabolism by these cells with a half-life in medium of approximately 40 h.
      [(3)H]I3C levels in media declined at a similar rate whether incubation was with
      cultured cells or in cell-free medium. Neither [(3)H]I3C nor its modified
      products accumulated in MCF-7 cells and only low levels of intact I3C were
      detected in cellular fractions. In contrast, I3C represented over 30% of the
      radioactivity in media even after 72 h. In cytosolic fractions, the 3-(cystein-S
      ylmethyl) and 3-(glutathion-S-ylmethyl) conjugates of [(3)H]I3C were the primary
      conversion products identified after 16 h, representing approximately 50% and
      approximately 15% of the radioactivity in these fractions, respectively. The
      reaction of I3C with thiols appears to be nonenzymatic since the cysteine
      conjugate is produced when I3C is incubated in cell-free medium containing
      additional cysteine. Both cellular and extracellular proteins were
      nonspecifically modified with [(3)H]I3C. In medium, proteins are radiolabeled
      even in the absence of cells, indicating again that enzymatic activation was not
      required. I3C was also oxidized to indole-3-carboxaldehyde and indole-3
      carboxylic acid in culture medium independent of cells. Unexpectedly, 3,3'
      diindolylmethane (DIM), an I3C product with in vitro and in vivo biological
      activity, was detected in cellular fractions and appeared to accumulate in the
      nucleus, representing approximately 40% of this fraction after 72 h treatment.
      These findings suggest that MCF-7 cells do not vigorously metabolize I3C and that
      the major route of reaction is with cellular thiols such as glutathione and
      proteins. The accumulation of DIM in the nucleus suggests that this product may
      have a role in the cellular biological activities of I3C.3

PMID- 11849036
TI  - Identification of conjugate adducts formed in the reactions of malonaldehyde
      acetaldehyde and malonaldehyde-formaldehyde with cytidine.
AB  - Malonaldehyde was reacted with cytidine in buffered aqueous solutions in the
      presence of acetaldehyde or formaldehyde. The reaction mixtures were analyzed by
      HPLC, and the products were isolated by preparative C18 chromatography and
      structurally characterized by UV absorbance, fluorescence emission, (1)H and
      (13)C NMR spectroscopy, and mass spectrometry. The major adducts formed in the
      reaction of malonaldehyde and acetaldehyde were identified as 7-(beta-D
      ribofuranosyl)-4-methyl-6-oxo-6,7-dihydro-4H-pyrimido[1,6-a]pyrimidine-3
      carbaldehyde (M(1)AA-Cyd) and 1-(beta-D-ribofuranosyl)-4-(3,5-diformyl-4-methyl
      1,4-dihydro-1-pyridyl)pyrimidine (M(2)AA-Cyd). In the reaction of malonaldehyde
      and formaldehyde, the major product was identified as 7-(beta-D-ribofuranosyl)-6
      oxo-6,7-dihydro-4H-pyrimido[1,6-a]pyrimidine-3-carbaldehyde (M(1)FA-Cyd). The
      highest yields of M(1)AA-Cyd and M(2)AA-Cyd, 3.2 and 0.5 mol %, respectively,
      were obtained in the reaction performed at pH 4.6 and 37 degrees C for 8 days,
      while M(1)FA-Cyd was produced at a yield of 0.3 mol % after 3 days of reaction at
      pH 4.0 and 37 degrees C. The products consist of units derived from malonaldehyde
      and acetaldehyde (M(1)AA-Cyd and M(2)AA-Cyd) or from malonaldehyde and
      formaldehyde (M(1)FA-Cyd), and are thus further examples of nucleoside
      modifications containing structural elements derived from aldehyde condensation
      reactions. Trace amounts of the adducts may be formed at physiological conditions
      and may be involved in the mutagenicity of the studied aldehydes.

PMID- 11849037
TI  - Fluorescence characteristics of site-specific and stereochemically distinct
      benzo[a]pyrene diol epoxide-DNA adducts as probes of adduct conformation.
AB  - Spectroscopic fluorescence quenching techniques are described for distinguishing
      the conformational characteristics of adducts derived from the binding of the
      benzo[a]pyrene metabolite anti-BPDE (the diol epoxide r7,t8-dihydroxy-t9,10epoxy
      7,8,9,10-tetrahydrobenz[a]pyrene) to the exocyclic amino groups of guanine ([BP]
      N(2)-dG) and adenine ([BP]-N(6)-dA) in double stranded oligonucleotides. These
      methods are calibrated by comparing the fluorescence quenching and UV absorbance
      characteristics of different, stereoisomeric anti-[BP]-N(2)-dG adducts of known
      adduct conformations, previously established by high-resolution NMR techniques.
      It is shown that intercalative adduct conformations can be distinguished from
      solvent-exposed adduct conformations, e.g., adducts in which the pyrenyl residues
      are positioned in the minor groove. These low resolution fluorescence methods are
      at least 4 orders of magnitude more sensitive than the high-resolution NMR
      techniques; the fluorescence methods are useful for distinguishing adduct
      conformations when either small amounts of material are available or the NMR
      signals are of such poor quality that high-resolution structures cannot be
      determined. This methodology is illustrated using a variety of anti-BPDE-modified
      oligonucleotides of varying adduct conformations. It is shown that the 10S (+)
      trans-anti-[BP]-N(6)-dA adduct in an oligonucleotide duplex containing an N-ras
      protooncogene sequence, believed to be conformationally heterogeneous and
      disordered, is significantly more exposed to the solvent environment than the
      stereoisomeric, intercalated 10R adduct [Zegar et al. (1996) Biochemistry 35,
      6212]. These differences suggest an explanation for the greater efficiencies of
      excision of the 10S adduct (relative to the 10R adduct) by human nucleotide
      excision repair enzymes [Buterin et al. (2000) Cancer Res. 60, 1849].

PMID- 11849038
TI  - Structure of an oligodeoxynucleotide containing a 1,N(2)-propanodeoxyguanosine
      adduct positioned in a palindrome derived from the Salmonella typhimurium
      hisD3052 gene: Hoogsteen pairing at pH 5.2.
AB  - The structure of the 1,N(2)-Propanodeoxyguanosine (PdG) adduct was determined at
      pH 5.2 in the oligodeoxynucleotide duplex 5'-d(CGCGGTXTCCGCG)3'.5'
      d(CGCGGACACCGCG)-3' (X = PdG). This sequence, referred to as the -TXT- sequence,
      is contained within the Salmonella typhimurium hisD3052 gene and contains a
      palindrome, representing a potential hotspot for frameshift mutagenesis. PdG
      provides a model for the primary adduct induced in DNA by malondialdehyde, the 3
      (2'-deoxy-beta-D-erythro-pentofuranosyl)pyrimido[1,2-a]-purin-10(3H)-one (M(1)G)
      lesion. The solution structure was refined by molecular dynamics calculations
      restrained by a combination of NMR-derived distances and dihedral angles, using a
      simulated annealing protocol. PdG introduced a localized perturbation into the
      sequence at base pair X(7).C(20), which was pH-dependent. At neutral pH,
      conformational exchange resulted in spectral line broadening, and it was not
      possible to determine the structure. A stable structure was observed at pH 5.2 in
      which PdG rotated about the glycosyl bond into the syn conformation. This placed
      the exocyclic moiety into the major groove of the duplex. PdG formed a protonated
      Hoogsteen pair with nucleotide C(20) in the complementary strand. The
      pseudorotation of the deoxyribose at C(20) was altered to an approximately equal
      blend of C2'-endo and C3'-endo structures. However, these made little difference
      in the overall structure of the modified oligodeoxynucleotide. The structure was
      compared to that of PdG in the 5'-d(CGCXCGGCATG)-3'.5'-(CATGCCGCGCG)-3' sequence
      (the -CXC- sequence) at pH 5.8 [Singh, U. S., Moe, J. G., Reddy, G. R.,
      Weisenseel, J. P., Marnett, L. J., and Stone, M. P. (1993) Chem. Res. Toxicol. 6,
      825-836]. A sequence effect was observed. When PdG was placed into the -TXT-
      sequence at low pH, the structural perturbation was limited to the X(7).C(20)
      base pair. In contrast, when PdG was placed into the -CXC- sequence at low pH,
      both the modified base pair and its 3'-neighbor base pair were disrupted. The
      results are discussed in the context of differential outcomes for site-specific
      mutagenesis and replication bypass experiments when PdG was placed in the -TXT-
      and -CXC- sequences, respectively.

PMID- 11849039
TI  - Structure of the 1,N(2)-propanodeoxyguanosine adduct in a three-base DNA hairpin
      loop derived from a palindrome in the Salmonella typhimurium hisD3052 gene.
AB  - The solution structure of the 1,N(2)-propanodeoxyguanosine (PdG) adduct was
      determined in a 3-base hairpin loop formed by d(CGCGGTXTCCGCG) (X = PdG). This
      sequence is contained within the Salmonella typhimurium hisD3052 gene, a hotspot
      for frameshift mutagenesis. PdG provides a structural model for the primary
      adduct induced in DNA by malondialdehyde, the 3-(2'-deoxy-beta-D-erythro
      pentofuranosyl)pyrimido[1,2-a]-purin-10(3H)-one (M(1)G) lesion. The solution
      structure of the PdG-containing hairpin was refined by molecular dynamics
      calculations restrained by a combination of NMR-derived distances and dihedral
      angles, using a simulated annealing protocol. The structure of the PdG-modified
      hairpin consisted of a five-base-pair stem and a three-base loop consisting of
      T(6), X(7), and T(8). T(6) projected into the minor groove of the stem adjacent
      to G(4). The modified base X(7) stacked on top of the duplex stem and wedged
      between bases T(8) and C(9). The PdG moiety was oriented such that the imidazole
      proton was facing the minor groove of the stem and the exocyclic protons
      projected into the major groove. The structure of the adducted hairpin was
      compared with the structure of the corresponding unmodified oligodeoxynucleotide,
      and was found to be similar. There was a minor difference in the backbone angles
      of the G and PdG Hairpins at the phosphate linkage between G(5) and T(6)
      involving the G(5) epsilon angle and T(6) alpha and beta angles. The PdG-modified
      hairpin exhibited an increase in T(m) of approximately 2 degrees C compared to
      the unmodified hairpin. The structural and thermodynamic similarities suggested
      that PdG does not stabilize this hairpin and thus may not promote its extrusion
      in duplex DNA. The structural results are correlated with the results of site
      specific mutagenesis experiments in the same sequence, which do not show evidence
      of frameshift mutations associated with hairpin loop formation. The geometry of
      this three-base loop is similar to that of other DNA hairpins containing three
      base loops, and suggests a common motif for the folding of these loops.

PMID- 11849040
TI  - A molecular motif required for the activation of rat neutrophil phospholipase
      A(2) by organochlorine compounds.
AB  - Organochlorine (OC) compounds are some of the main toxicants present in the food
      web and target several cellular systems including the nonspecific immune system.
      The objective of this study was to test the hypothesis that OC compounds that
      activate neutrophils share common structural features. Using activation of
      phospholipase A(2) (PLA(2)) as a marker of neutrophil activation, isolated rat
      neutrophils were exposed to a variety of OC compounds. The ortho-substituted
      polychlorinated biphenyl 2,2',4,4'-tetrachlorobiphenyl, the alpha-, delta-, and
      gamma-isomers of hexachlorocyclohexane (HCCH), p,p'
      dichlorodiphenyltrichloroethane (DDT), dieldrin, and chlordane each induced
      activation of PLA(2) in neutrophils. Beta-HCCH and the non-ortho-substituted
      3,3',4,4'-tetrachlorobiphenyl were without effect. PLA(2) activation stimulated
      by each of the OC compounds was reduced by methyl arachidonyl fluorophosphonate,
      which inhibits both a cytosolic and a calcium-independent PLA(2) (iPLA(2)), and
      by E-6-(bromoethylene)tetrahydro-3-(1-naphthalenyl)-2H-pyran-2-one (BEL), a
      selective inhibitor of iPLA(2). These results suggest that a fraction of the
      PLA(2) activity stimulated by OC compounds is dependent on iPLA(2). Western
      analysis confirmed the presence of iPLA(2) in rat neutrophils. Molecular modeling
      techniques were used to develop structure-activity relationships for the
      activation of PLA(2) by OC compounds. Superimposing three-dimensional structures,
      an electrotopological motif shared by all of the active compounds was identified.
      This motif was absent in the inactive beta-HCCH and 3,3',4,4'
      tetrachlorobiphenyl. This motif, which we have called PHEN, is required for the
      activation of the neutrophil PLA(2) by OC compounds and consists of a planar
      hydrophobic domain connected rigidly at a perpendicular angle to a halogen atom.

PMID- 11849041
TI  - Genotoxic mechanism for the major acrolein-derived deoxyguanosine adduct in human
      cells.
AB  - Acrolein, widely distributed in the environment and also produced endogenously,
      forms deoxyguanosine adducts in DNA. The genotoxicity of the major acrolein-dG
      adduct, 8alpha and 8beta isomers of 3H-8-hydroxy-3-(beta-D-2'-deoxyribofuranosyl)
      5,6,7,8-tetrahydropyrido[3,2-a]purine-9-one (gamma-OH-PdG), and the model adduct,
      PdG, which lacks the hydroxy group of gamma-OH-PdG, was investigated in human
      cells. The adducts were site-specifically incorporated into a SV40/BK origin
      based shuttle vector. Estimated efficiencies of translesion DNA synthesis were
      73% for gamma-OH-PdG and 25% for PdG when compared with dG control. Gamma-OH-PdG
      was marginally miscoding (<or=1%), inducing G-->T and G-->A base substitutions in
      HeLa and xeroderma pigmentosum complementation group A (XP-A) and variant (XP-V)
      cells. There was no significant difference in the miscoding frequency when the
      adduct was inserted in the leading or lagging strand. PdG was more miscoding than
      gamma-OH-PdG by inducing targeted base substitutions (G-->T, A, or C) at a
      frequency of 7.5% in XP-A cells. Thus, the authentic major adduct, gamma-OH-PdG,
      is less blocking to DNA synthesis and less miscoding than the model adduct, PdG.

PMID- 11849042
TI  - Mutagenesis by O(6)-[4-oxo-4-(3-pyridyl)butyl]guanine in Escherichia coli and
      human cells.
AB  - Site-specific mutagenesis by O(6)-[4-oxo-4-(3-pyridyl)butyl]guanine (O(6)
      pobGua), a product of DNA pyridyloxobutylation by metabolites of the tobacco
      specific nitrosamines N-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3
      pyridyl)-1-butanone (NNK), was studied in Escherichia coli strain DH10B and human
      kidney cells (293) when the modified base was incorporated in either a double
      stranded or a gapped shuttle vector. In the repair-competent E. coli strain, less
      than 3% of the colonies produced by double-stranded vectors harboring the
      modified base were mutant whereas 96% were mutant when DH10B cells were
      transformed with modified gapped vectors. By contrast, transformation of DH10B
      cells with plasmids derived from O(6)-pobGua-containing double-stranded and
      gapped vectors previously replicated in 293 cells produced 7 and 16% mutant
      colonies, respectively. These percentages increased to 42 and 82%, respectively,
      when the 293 cells were pretreated with O(6)-benzylguanine to inactivate the O(6)
      alkylguanine-DNA alkyltransferase protein. These findings confirm that the adduct
      is readily repaired by the human O(6)-alkylguanine-DNA alkyltransferase in both
      double-stranded and gapped vectors and suggest that it is also highly mutagenic
      in both human cells and E. coli. In the E. coli strain, the adduct produced
      exclusively G --> A transition mutations although in human 293 cells it also
      produced G --> T transversions and more complex mutations in addition to G --> A
      transitions. These data suggest that O(6)-[4-oxo-4-(3-pyridyl)butyl]guanine can
      contribute significantly to the mutagenic risk posed by exposure to both NNN and
      NNK in tobacco smoke.

PMID- 11849043
TI  - Glutathione conjugation and DNA adduct formation of dibenzo[a,l]pyrene and
      benzo[a]pyrene diol epoxides in V79 cells stably expressing different human
      glutathione transferases.
AB  - Mammalian V79 cells stably expressing human glutathione transferase (GST) A1-1,
      M1-1, and P1-1 (the allelic variant with Val105 and Ala114) have been constructed
      and characterized. The cells have been used to study the capacity of individual
      GST isoenzymes in conjunction with GSH to detoxify diol epoxides from
      dibenzo[a,l]pyrene (DBPDE), the most carcinogenic polycyclic aromatic hydrocarbon
      (PAH) identified so far, and diol epoxides from benzo[a]pyrene (BPDE). The
      relationship between GSH-conjugation and DNA adduct-formation has been
      investigated as well as factors governing the accessibility of lipophilic diol
      epoxide substrates for the soluble GSTs in the cells. Relative to control cells,
      those expressing GSTA1-1 showed the highest rate (about 50-fold increase) to
      perform GSH-conjugation of (-)-anti-DBPDE (R-absolute configuration at the
      benzylic oxirane carbon in the fjord-region) followed by GSTM1-1 (25-fold
      increase) and GSTP1-1 (10-fold increase). GSTA1-1 was found to be strongly
      inhibited when expressed in cells (10% of fully functional protein). Taking this
      factor into account, the rates of conjugation found in the cells fairly well
      reflected the order of catalytic efficiencies (k(cat)/K(m)) obtained with the
      pure enzymes. Increased GSH conjugation of (-)-anti-DBPDE was associated with a
      reduction in DNA adduct formation. GSTA1-1 inhibited the formation of adducts
      more than 6-fold and GSTM1-1 and GSTP1-1 about 2-fold. With (+)-anti-BPDE, GSTP1
      1-expressing cells demonstrated a substantially higher rate of GSH-conjugate
      formation than cells with GSTA1-1 and GSTM1-1 cells (33- and 10-fold increase,
      respectively). Relative to control cells, GSTM1-1 was found to inhibit DNA adduct
      formation of (+)-anti-BPDE most effectively followed by GSTP1-1 and GSTA1-1 (12-,
      4-, and 3-fold, respectively). Values of k(cat)/K(m) and estimated oil/water
      partition coefficients of DBPDE and BPDE were used to calculate the concentration
      of free diol epoxides in solution and expected rates of GSH conjugate formation
      in cells, and these theoretical results were compared with the observed ones.
      With the highly reactive (+)-anti-BPDE, 1-2% of the expected activity was
      observed, whereas the corresponding values for the less reactive (-)-anti-DBPDE
      were up to 13%. The most obvious explanations for the low observed rate with (+)
      anti-BPDE are rapid and competing reactions such as hydrolysis and/or more
      unspecific chemical and physical reactions with cellular constituents (proteins,
      lipids, nucleic acids, etc.). In addition, the difference between the theoretical
      and observed rates may also reflect participation of factors such as
      macromolecular crowding and reduced rates of diffusion, factors expected to
      further restrict the accessibility of GST and the diol epoxides in the intact
      cell.

PMID- 11849044
TI  - Inhibition of cell proliferation and AP-1 activity by acrolein in human A549 lung
      adenocarcinoma cells due to thiol imbalance and covalent modifications.
AB  - Acrolein, a reactive alpha,beta-unsaturated aldehyde, is a common environmental
      pollutant, a metabolite of the anticancer drug cyclophosphamide, and a byproduct
      of lipid peroxidation. An increase in acrolein production has been proposed as a
      marker for Alzheimer's disease, diabetic glomerular lesions, and atherosclerosis.
      Acrolein is a potent inhibitor of cell proliferation at nonlethal doses and may
      act through effects on redox-regulated transcription factors. We previously
      reported that NF-kappaB activation is inhibited by acrolein in the A549 lung
      adenocarcinoma cell line in an IkappaB-independent manner [Horton et al. (1999)
      J. Biol. Chem. 274, 9200-9206]. The current data demonstrate that AP-1 activation
      in A549 cells is decreased by 26 and 50% at 0.5 and 1 h, respectively, after
      exposure to 50 fmol/cell (a nonlethal dose) of acrolein. Inhibition of AP-1
      activation also occurred following treatment with buthionine sulfoximine to
      deplete glutathione to the same extent as seen with acrolein. c-jun antisense
      treatments depressed c-jun protein below detectable levels at 4 h and inhibited
      cell proliferation (as assessed by [(3)H]thymidine incorporation) by 80%.
      Immunoprecipitation of c-jun protein after treating A549 cells with acrolein
      revealed the presence of a lysine-acrolein adduct. There was, however, no effect
      of acrolein on c-jun N-terminal kinase activity or c-jun phosphorylation. These
      data indicate that the inhibition of cell proliferation induced by acrolein
      correlates with the depletion of glutathione as well as the inhibition of AP-1
      activation. AP-1 activation is likely affected both through changes in cellular
      thiol redox balance and by covalent modification of acrolein to c-jun, but not
      through effects on c-jun phosphorylation.

PMID- 11849045
TI  - Characterization of DNA adducts and tetraols derived from anti
      benzo[ghi]fluoranthane-3,4-dihydrodiol-5,5a-epoxide.
AB  - A total of seven DNA adducts and two racemic tetraols derived from anti
      benzo[ghi]fluoranthene-3,4-dihydrodiol-5,5a-epoxide (anti-B[ghi]FDE, 2) were
      characterized by analyses of UV, (1)H NMR, CD, and MALDI mass spectra. The
      structure of 2 is the first example of a diolepoxide in which a fully fused
      cyclopentane ring is covalently linked to the saturated ring bearing the epoxide
      function. Compound 2 is also a conformationally rigid structure analogue of the
      extensively studied anti-benzo[c]phenanthrene-3,4-dihydrodiol-1,2-epoxide (anti
      BcPDE), thus serving as a model for probing the diolepoxide-DNA interaction
      [Chang et al. (2002) Chem. Res. Toxicol. 15, 198-208 (following paper in this
      issue)]. The most abundant adducts are formed from trans- or cis-openings of the
      epoxide by the amino groups of either deoxyguanosine or deoxyadenosine. Adducts
      of minor abundance formed by the attachment of the diolepoxide to the amino group
      of deoxycytidine N(4) and guanine N(7) were also isolated. Post-source decay
      MALDI spectra of the (M + H)(+) molecule ions are consistent with the assigned
      adduct structures. The lack of a typical benzylic proton at the site of
      deoxynucleoside attachment necessitated a new NMR assignment strategy. Despite
      the steric constraint, the epoxide ring opening of 2 occurred exclusively at the
      dibenzylic C5a, not at C5. The assignments on the trans- and cis-epoxide opening
      were made based on the molecular modeling structures, i.e., the pseudoaxial H5 in
      cis-adducts is placed directly under the strong influence of a shielding cone of
      the aromatic ring system, while the same proton in trans-adducts adopts a
      pseudoequatorial conformation, thereby protruding away from the aromatic ring
      system. The absolute configuration at the site of deoxynucleoside attachment
      (C5a) was tentatively assigned on the basis of the empirical rules that have been
      established for deoxynucleoside-adducts derived from traditional alternant PAH
      diolepoxides.

PMID- 11849046
TI  - Characterization of DNA adducts derived from syn-benzo[ghi]fluoranthene-3,4
      dihydrodiol-5,5a-epoxide and comparative DNA binding studies with structurally
      related anti-diolepoxides of benzo[ghi]fluoranthene and benzo[c]phenanthrene.
AB  - This paper reports structural characterization of the adducts and tetraols formed
      from syn-benzo[ghi]fluoranthene-3,4-dihydrodiol-5,5a-epoxide (syn-B[ghi]FDE, 3)
      and comparative DNA-binding and mutagenicity studies involving 3, anti-B[ghi]FDE
      (2), and anti-benzo[c]phenanthrene-11,12-dihydrodiol-13,14-epoxide (anti-BcPDE,
      5). The structures of nine DNA adducts and two racemic tetraols derived from 3
      have been determined spectroscopically. Similar characterization of adducts
      obtained from the anti-isomer 2 was described in the preceding paper in this
      issue [Chang et al. (2002) Chem. Res. Toxicol. 15, 187-197]. The majority of DNA
      adducts with 3 are those from the trans- or cis-opening of the epoxide at C5a by
      the exocyclic amino groups of dG, dA, and dC. The diolepoxides 2 and 3 are rigid
      structure analogues of anti- and syn-BcPDE (5 and 6), respectively, thus serving
      as models for probing molecular deformity and diol conformation in diolepoxide
      DNA interaction. Comparative DNA binding experiments indicate that 57% of 2 and
      33% of 3 were converted into DNA adducts, whereas a 71% conversion was observed
      for 5. In general, lower percentages were observed with denatured calf-thymus
      DNA. As for base selectivity, 2 showed a greater affinity for dA relative to dG
      (dA/dG ratio, 0.79) than 3 (0.56) when reacted with native calf-thymus DNA. A
      much higher dA/dG ratio (1.41) was obtained for 5. The overall dA/dG ratios were
      lower with denatured DNA, indicating the importance of the secondary structure of
      DNA for both adduct formation and chemical selectivity. The T-shape pseudo
      diaxial diols of 3 appears to have favorable electrostatic interactions with the
      nearby phosphate backbone in the minor groove of DNA, thereby yielding greater
      amounts of dG adducts than the pseudo-diequatorial 2. The anti-isomer 2 was found
      to be seven times more mutagenic than 3, but they are significantly less
      mutagenic than the nonplanar analogue 5 when tested in Salmonella typhimurium TA
      100.

PMID- 11849047
TI  - Identification of a S-hexahydro-1H-azepine-1-carbonyl adduct produced by molinate
      on rat hemoglobin beta(2) and beta(3) chains in vivo.
AB  - Molinate is a thiocarbamate herbicide used in the rice industry for over 25
      years, and regulatory reports have shown that administration of molinate results
      in reproductive toxicity in male rats. Previous in vitro studies indicate that
      molinate undergoes oxidative metabolism, forming reactive electrophilic
      intermediates capable of undergoing nucleophilic addition by protein
      nucleophiles. On the basis of in vitro studies, carbamylation of an active site
      serine residue in Hydrolase A has been proposed to be the mechanism responsible
      for the observed testicular toxicity. The experiments presented here utilize
      hemoglobin to characterize covalent protein modifications produced in vivo by
      molinate. Rats were dosed intraperitoneally with molinate as a function of
      exposure duration. Examination of globin from molinate-treated rats by HPLC
      demonstrated a new peak in the isolated samples and, when collected and analyzed
      using MALDI-TOF MS, revealed a 126 Da increase in mass relative to the native
      beta(3) chain. Digestion of the globin using Glu-C and analysis by MALDI-TOF MS
      revealed two modified peptide fragments at m/z 2743 and 4985 consistent with a
      126 Da increase to peptide fragments [122-146] and [102-146] in the unmodified
      beta(2) and beta(3) chains of globin. Using selected reaction monitoring
      LC/MS/MS, S-hexahydro-1H-azepine-1-carbonyl cysteine (HHAC-Cys) was identified in
      the globin hydrolysates isolated from the molinate-treated rats, but not in the
      control samples, and the quantity of adduct exhibited a cumulative dose response.
      These experiments demonstrate the ability of molinate to covalently modify
      proteins in vivo in a dose dependent manner. For hemoglobin this modification was
      a carbamylation at Cys-125 similar to the modification produced by disulfiram and
      N,N-diethyldithiocarbamate. The ability of molinate to covalently modify cysteine
      residues provides a potential mechanism to account for enzyme inhibition
      following molinate exposure and suggests that enzymes with cysteine residues in
      their active site may be inhibited by molinate.

PMID- 11849048
TI  - Preparation of oligodeoxynucleotides containing a diastereoisomer of alpha-(N(2)
      2'-deoxyguanosinyl)tamoxifen by phosphoramidite chemical synthesis.
AB  - Women treated with an antiestrogen tamoxifen (TAM) for endocrine therapy or
      prevention of breast cancer show an increased risk of developing endometrial
      cancer. TAM-DNA adducts have been detected in the liver of rodents treated with
      TAM and in the endometrium of women taking TAM. The major TAM adducts have been
      identified as diastereoisomers of trans- and cis-forms of alpha-(N(2)
      deoxyguanosinyl)tamoxifen (dG-N(2)-TAM) and alpha-(N(2)-deoxyguanosinyl)-N
      desmethyltamoxifen. In the study presented here, we prepared
      oligodeoxynucleotides containing a diastereoisomer of dG-N(2)-TAM by
      phosphoramidite chemical synthesis. Initially, the trans- and cis-forms of alpha
      aminotamoxifen (alpha-NH(2)-TAM) were synthesized from alpha-hydroxytamoxifen
      using the Mitsunobu reaction followed by hydrolysis. Thereafter by coupling the
      trans- and cis-form of alpha-NH(2)-TAM with the DMT-derivative of 2-fluoro-(O(6)
      2-(trimethylsilyl)ethyl)-2'-deoxyinosine, the trans- and cis-forms of DMT-dG-N(2)
      TAM, respectively, were prepared in high yield and used in the preparation of the
      phosphoramidite precursors. Large quantities of oligodeoxynucleotides containing
      a trans- or a cis-form of dG-N(2)-TAM were prepared efficiently by automated DNA
      synthesizer. The incorporation of dG-N(2)-TAM adduct into the
      oligodeoxynucleotides was confirmed using (32)P-postlabeling/polyacrylamide gel
      electrophoresis analysis. These site-specifically modified oligodeoxynucleotides
      will be used for exploring biological properties and three-dimensional structure
      of TAM-DNA adducts.

PMID- 11849050
TI  - Regioisomeric synthesis and characteristics of the alpha-hydroxy-1,N(2)
      propanodeoxyguanosine.
AB  - Acrolein, a known mutagen, undergoes reaction in vitro under physiological
      conditions with both 2'-deoxyguanosine and native DNA to give rise to exocyclic
      adducts of the 5,6,7,8-tetrahydropyrimido[1,2-a]purine-10(3H)-one class having a
      hydroxyl group at either the 6 or the 8 position (these positions are
      respectively designated alpha and gamma when referring to the 1,N(2)-(propano
      bridge). Previously, we have shown that the 8-hydroxy derivative has very low
      mutagenicity probably because, in double-stranded DNA, this residue exists in the
      open-chain aldehydic form [N(2)-(3-oxopropyl)-2'-deoxyguanosine] (5). To continue
      our investigation in this area, we needed ample supplies of the 6-hydroxy
      isomers. This current paper describes high-yield simple methods for the synthesis
      in bulk of the 6-hydroxy and the 6-methoxy exocyclic adducts 1 and 3 and a new
      efficient synthesis of 1,N(2)()-(prop-1,3-diyl)-2'-deoxyguanosine (4), previously
      used as a chemically stable model in studying the physico-biological implications
      of 1,N(2) exocyclic adduction to dG.

PMID- 11849049
TI  - Role of cytochrome P450 1a1 and 1b1 in the metabolic activation of 7,12
      dimethylbenz[a]anthracene and the effects of naturally occurring furanocoumarins
      on skin tumor initiation.
AB  - The current study was designed to determine the mechanistic basis for differences
      in the effects of naturally occurring furanocoumarins on skin tumor initiation by
      7,12-dimethylbenz[a]anthracene (DMBA). Female SENCAR mice were pretreated
      topically with bergamottin, imperatorin, or isopimpinellin (100-3200 nmol), 7,8
      benzoflavone (7,8-BF, 5-40 nmol, a known inhibitor of DMBA skin carcinogenesis in
      mice), or acetone (vehicle control) 5 min prior to topical treatment with DMBA
      (10 nmol). Imperatorin, isopimpinellin, and 7,8-BF, but not bergamottin,
      significantly blocked total DMBA-DNA adduct formation. HPLC analysis of DNA
      adducts revealed that bergamottin preferentially inhibited formation of anti-DMBA
      diol-epoxide (DMBADE) derived DNA adducts, imperatorin, and isopimpinellin
      inhibited both anti- and syn- derived adducts, whereas 7,8-BF showed some
      selectivity for reduction of syn-DMBADE-DNA adducts. Mouse embryo fibroblast
      C3H/10T1/2 (10T1/2) cells, and mouse hepatoma-derived 1c1c7 (Hepa-1) cells, which
      preferentially express P450 1b1 and P450 1a1, respectively, were co-incubated
      with 2 microM bergamottin, imperatorin, isopimpinellin, and 7,8-BF, and with DMBA
      (2 microM). Hepa-1 cells (P450 1a1) formed mainly anti-DMBADE-DNA adducts. In
      contrast, 10T1/2 cells (P450 1b1) formed mainly syn-DMBADE-DNA adducts.
      Bergamottin inhibited DMBA metabolism to DMBA-3,4-diol and blocked DNA adduct
      formation in Hepa-1 cells, but had little effect in 10T1/2 cells. In contrast,
      7,8-BF completely blocked DMBA metabolism and DNA adduct formation in 10T1/2
      cells, but had little effect in Hepa-1 cells. Imperatorin and isopimpinellin
      inhibited DMBA bioactivation in both cell lines. These results indicate that
      bergamottin is a more selective inhibitor of P450 1a1 and overall a less
      effective inhibitor of the metabolic activation of DMBA in mouse epidermis. In
      contrast, imperatorin, isopimpinellin, and especially 7,8-BF, which block
      metabolic activation of DMBA in mouse epidermis, appear more selective for P450
      1b1. On the basis of our studies using 10T1/2 cells and Hepa-1 cells, it appears
      that P450 1a1 is primarily responsible for converting DMBA-3,4-diol to anti
      DMBADE, whereas P450 1b1 is primarily responsible for converting DMBA-3,4-diol to
      syn-DMBADE. These data demonstrate the role of P450 1a1 and 1b1 in the metabolic
      activation of DMBA in mouse epidermis and provide a mechanistic explanation for
      the differential effects of naturally occurring furanocoumarins (and 7,8-BF) on
      polycyclic aromatic hydrocarbon skin carcinogenesis.

PMID- 11849051
TI  - Glutathione-dependent metabolism of the antitumor agent sulofenur. Evidence for
      the formation of p-chlorophenyl isocyanate as a reactive intermediate.
AB  - The antitumor agent sulofenur (LY186641), which has shown promising activity
      against a wide range of cancers, causes hemolytic anemia and methemoglobinemia at
      dose-limiting toxicities. The antitumor and toxicological mechanism(s) of action
      of the drug is (are) not well understood, but unlike other antineoplastic agents,
      sulofenur does not interfere with DNA, RNA, or protein synthesis, or with
      polynucleotide function. In the present study, we evaluated the hypothesis that
      sulofenur undergoes bioactivation in vivo to generate p-chlorophenyl isocyanate
      (CPIC), which could carbamoylate biological macromolecules directly or form a
      conjugate with glutathione (GSH) which would serve as a latent form of CPIC. The
      objectives of this study, therefore, were to determine if the GSH and N
      acetylcysteine conjugates of CPIC were excreted into bile and urine,
      respectively, after an i.p. dose of sulofenur to rats. In addition, the chemical
      stability and thiol exchange properties of these S-linked conjugates were
      determined. The results of this study indicate that sulofenur does undergo
      metabolism in vivo to yield the GSH conjugate of CPIC, and that this conjugation
      reaction is reversible and subject to thiol exchange in buffered aqueous solution
      (pH 7.4, 37 degrees C). In contrast, sulofenur itself was stable under these same
      conditions, even in the presence of GSH and glutathione-S-transferase (GST), thus
      raising the possibility that bioactivation of sulofenur is necessary for
      liberation of CPIC. These findings suggest that the generation of this isocyanate
      in vivo and subsequent carbamoylation of biological macromolecules may play a
      role in the toxicity and/or antitumor activity of sulofenur and related
      diarylsulfonylureas.

PMID- 11849053
TI  - Detection and quantification of 5-chlorocytosine in DNA by stable isotope
      dilution and gas chromatography/negative ion chemical ionization/mass
      spectrometry.
AB  - Hypochlorous acid (HOCl) is generated from activated phagocytes during infections
      and inflammation. One of the major products of HOCl reaction with DNA was 5
      chlorocytosine (5Cl-Cyt). In this report, a gas chromatography/negative ion
      chemical ionization/mass spectrometry (GC/NICI/MS) assay with stable isotope
      dilution was developed for detection and quantification of 5Cl-Cyt in DNA. During
      hydrolysis of DNA, 5Cl-Cyt undergoes spontaneous deamination quantitatively
      forming 5-chlorouracil (5Cl-Ura). The stable isotope of 5Cl-Ura with six mass
      units higher than the normal 5Cl-Ura was synthesized and used as internal
      standard of the assay. The adduct-enriched fraction of DNA hydrolysate was
      derivatized with pentafluorobenzyl bromide before GC/NICI/MS analysis with
      selected ion monitoring at [M - 181](-) fragments of bispentafluorobenzylated 5Cl
      Ura and its isotope analogue. The limit of detection was 20 amol (S/N = 8) of
      bispentafluorobenzylated 5Cl-Ura injected on column with selective ion monitoring
      mode and the limit of quantification for the entire assay was 14 fmol of 5Cl-Cyt.
      Analysis of hypochlorous acid-treated calf thymus DNA by both GC/NICI/MS and
      HPLC/UV detection provided similar adduct levels and thus verified this new
      GC/NICI/MS assay. Using this highly specific and ultrasensitive GC/NICI/MS
      method, the levels of 5Cl-Cyt in untreated calf thymus DNA and human placental
      DNA were determined as 0.6 and 6.6 adducts per 10(7) normal cytosine,
      respectively. Peroxynitrite also contributed to 5Cl-Cyt formation in DNA. Level
      of 5Cl-Cyt in DNA treated with peroxynitrite in the presence of chloride was
      higher than that without addition of chloride. Thus, quantification of 5Cl-Cyt in
      DNA by this isotope dilution GC/NICI/MS assay may facilitate research on the role
      of DNA chlorination in carcinogenesis and in cancer development.

PMID- 11849052
TI  - Synthesis and characterization of site-specific and stereoisomeric fjord
      dibenzo[a,l]pyrene diol epoxide-N(6)-adenine adducts: unusual thermal
      stabilization of modified DNA duplexes.
AB  - The fjord polycyclic aromatic hydrocarbon compound dibenzo[a,l]pyrene (DB[a,l]P)
      is significantly more tumorigenic than the bay region benzo[a]pyrene in animal
      model systems. The molecular origins of the unusually strong genotoxic properties
      of DB[a,l]P and its fjord region diol epoxide metabolites are of great interest
      and are believed to be related to the structural characteristics of the DNA
      adducts formed. Site-specifically modified oligonucleotides were prepared by
      reacting the single adenine residue in 5'-d(CTCTCACTTCC) (I) with the racemic
      fjord diol epoxide r11,t12-dihydrodiol-t13,14-epoxide-11,12,13,14
      tetrahydrodibenzo[a,l]pyrene (anti-DB[a,l]PDE) in aqueous solutions. Four
      different oligonucleotides I with the single adenosine residues involving a
      covalent bond between the C14 position of DB[a,l]PDE and N(6)-dA are identified
      and purified. The CD spectra of the mononucleotide adducts are similar to those
      of Li et al. [Li et al. (1999) Chem. Res. Toxicol. 12, 758] who characterized
      DB[a,l]PDE-N(6)-dA adducts by a combination of CD and NMR methods. The
      stereochemical properties of each of the four DB[a,l]PDE-modified
      oligonucleotides were assigned on the basis of a combination of empirical CD
      rules and other approaches and differ from those of Li et al. The thermal melting
      points, T(m), of the unmodified duplex of I with its complementary strand (IC),
      T(m) = 43.8 +/- 0.5 degrees C, were compared with the same duplexes containing
      stereoisomeric anti-DB[a,l]PDE-N(6)-dA lesions. The T(m) of duplexes I.IC
      containing lesions with R absolute configurations at C14 of the DB[a,l]PDE
      residues are greater by 6-8 degrees C, while those with S configuration are lower
      by 6-10 degrees C. Similar effects are observed with adducts in the same sequence
      context derived from the fjord PAH anti-diol epoxides of benzo[g]chrysene, while
      duplexes containing lesions derived from benzo[c]phenanthrene diol epoxides with
      1R and 1S configurations exhibit unchanged T(m) values. In contrast, the T(m)
      values of duplexes with lesions derived from the bay region benzo[a]pyrene diol
      epoxides (B[a]PDE) in the same sequence are lower by 12 degrees (10R adducts) and
      by 19 degrees (10S adducts). The greater thermal stabilities of duplexes with
      fjord PAH-N(6)-dA lesions relative to those with bay region B[a]PDE-N(6)-dA
      adducts, are correlated with lower susceptibilities of excision by human
      nucleotide excision repair enzymes [Buterin et al. (2000) Cancer Res. 60, 1849].
      The implications of these relationships are discussed in terms of present
      knowledge of the conformations of fjord and bay region PAH diol epoxide-N(6)-dA
      lesions in double stranded DNA.

PMID- 11849055
TI  - Synthesis, characterization, and preliminary intramolecular energy transfer
      studies of rigid, emissive, rhenium-linked porphyrin dimers.
AB  - The reaction of pyridyl functionalized porphyrins with Re(CO)(5)Cl in THF results
      in the formation of porphyrin dimers which, despite incorporation of rhenium into
      the assemblies, remain fluorescent. The rigid compounds provide an efficient
      geometry and/or orbital pathway for singlet energy transfer, rendering these
      compounds suitable, in principle, for the study of both through-bond and through
      space energy transfer. Derivatives containing both metallated and freebase
      porphyrins connected via the metal corners display efficient porphyrin-porphyrin
      energy transfer. The photophysical properties of the assemblies have been studied
      by both steady-state and time-resolved fluorescence techniques, yielding
      approximate rates and efficiencies for porphyrin-porphyrin energy transfer.

PMID- 11849054
TI  - Reactivity of hydroperoxide bound to a mononuclear non-heme iron site.
AB  - The first isolation and spectroscopic characterization of the mononuclear
      hydroperoxo-iron(III) complex [Fe(H(2)bppa)(OOH)](2+) (2) and the stoichiometric
      oxidation of substrates by the mononuclear iron-oxo intermediate generated by its
      decomposition have been described. The purple species 2 obtained from reaction of
      [Fe(H(2)bppa)(HCOO)](ClO(4))(2) with H(2)O(2) in acetone at -50 degrees C gave
      characteristic UV-vis (lambda(max) = 568 nm, epsilon = 1200 M(-1) cm(-1)), ESR (g
      = 7.54, 5.78, and 4.25, S = (5)/(2)), and ESI mass spectra (m/z 288.5
      corresponding to the ion, [Fe(bppa)(OOH)](2+)), which revealed that 2 is a high
      spin mononuclear iron(III) complex with a hydroperoxide in an end-on fashion. The
      resonance Raman spectrum of 2 in d(6)-acetone revealed two intense bands at 621
      and 830 cm(-1), which shifted to 599 and 813 cm(-1), respectively, when reacted
      with (18)O-labeled H(2)O(2). Reactions of the isolated (bppa)Fe(III)-OOH (2) with
      various substrates (single turnover oxidations) exhibited that the iron-oxo
      intermediate generated by decomposition of 2 is a nucleophilic species formulated
      as [(H(2)bppa)Fe(III)-O*].

PMID- 11849056
TI  - New method to prepare polycrystalline meta-thioboric acid, (HBS(2))(3).
AB  - A new method to prepare polycrystalline meta-thioboric acid (c-HBS(2)) has been
      developed and reported. HBS(2) was obtained as a vapor condensate by reacting
      H(2)S with B(2)S(3) in the vapor phase, and the optimal conditions for this
      reaction are reported. The X-ray and spectroscopic characterization suggest that
      the structure of thioboric acid is monoclinic and made up of hexagonal rings
      formed by trimer units, (HBS(2))(3). The present preparation route is facile,
      faster than other wet routes of thiolysis, and the reaction requires much lower
      temperatures, thus avoiding contamination by reactor materials.

PMID- 11849058
TI  - Carboranes as ligands for the preparation of organometallic Tc and Re
      Radiopharmaceuticals. Synthesis of [M(CO)(3)(eta-2,3-C(2)B(9)H(11))](-) and rac
      [M(CO)(3)(eta-2-R-2,3-C(2)B(9)H(10))](-) (M = Re, (99)Tc; R = CH(2)CH(2)CO(2)H)
      from [M(CO)(3)Br(3)](2-).
AB  - A new and high yielding method for the synthesis of [M(CO)(3)(eta(5)-2,3
      C(2)B(9)H(11))](-) and the bifunctional metal complexes, rac-[M(CO)(3)(eta(5)-2-R
      2,3-C(2)B(9)H(10))](-) (R = CH(2)CH(2)CO(2)H), from [M(CO)(3)Br(3)](2)(-) (M =
      Re, (99)Tc) was developed. The general approach entailed the addition of nido
      [(C(2)B(9)H(12))(-)], or the acid substituted analogue, to [M(CO)(3)Br(3)](2)(-)
      (M = Re, (99)Tc) in the presence of TlOEt in THF. It was also possible to prepare
      the reported products in water using sodium carbonate in place of TlOEt. The
      reported approach led to the preparation, and X-ray crystallographic structure
      determination, of the first Tc-carborane complex reported to date (a = 13.606(17)
      A, b = 10.685(13) A, c = 15.534(16) A, alpha = gamma = 90 degrees, beta =
      111.84(2) degrees). Because of the stabilities of the metal complexes, and the
      fact that the compounds can be prepared in water, the bifunctional derivatives
      can be considered as novel synthons for the preparation of organometallic (99m)Tc
      and (186/188)Re radiopharmaceuticals.

PMID- 11849057
TI  - Reactivity of the B-H Bond in tris(pyrazolyl)hydroborato zinc complexes:
      unexpected example of zinc hydride formation in a protic solvent and its
      relevance towards hydrogen transfer to NAD(+) mimics by
      tris(pyrazolyl)hydroborato zinc complexes in alcoholic media.
AB  - Solutions of the zinc hydroxide complex [Tp(Bu(t),Me)]ZnOH in alcohols (ROH; R =
      Me, Et, Pr(i)) achieve hydride transfer to the NAD(+) model, 10-methylacridinium
      perchlorate. Deuterium labeling studies, however, demonstrate that the source of
      the hydride is not the alcohol but, rather, the B [bond] H group of the
      [Tp(Bu(t),Me)] ligand. A further example in which a [Tp(Bu(t),Me)] ligand acts as
      a hydride donor is provided by the reaction of the aqua complex
      [[Tp(Bu(t),Me)]Zn(OH(2))][HOB(C(6)F(5))(3)] with MeOH to generate the zinc
      hydride complex [Tp(Bu(t),Me)]ZnH. The present study therefore provides a caveat
      for the often assumed inertness of the B [bond] H group in
      tris(pyrazolyl)hydroborato ligands, especially in the presence of reactive
      cationic species.

PMID- 11849059
TI  - 1,3,5-Triazine templated self-assembly of a hexameric copper(I) chloride
      triphenyl phosphite core.
AB  - The reaction of CuCl, P(OPh)(3), and 1,3,5-triazine (Trz) in CHCl(3) produces
      [(CuCl)(6)(P(OPh)(3))(6)(Trz)(2)] via molecular self-assembly. An X-ray
      structural study has revealed a D(3d) symmetry hexamer containing an oblate
      spheroid core. The core consists of a Cu(6)Cl(6) macrocycle, which is capped by
      two mu(3)-Trz ligands. Seven parallel stacked atom planes are present: P(3), Trz,
      Cu(3), Cl(6), Cu(3), Trz, and P(3). The six copper atoms are not coplanar with
      the Trz ligands and form a distorted octahedron. Crystal data: triclinic P macro
      1, a = 14.1489(7) A, b = 15.7470(8) A, c = 29.6572(14) A, alpha = 76.4330(10)
      degrees, beta = 79.5120(10) degrees, gamma = 72.2260(10) degrees, V = 6088.5(5)
      A(3), Z = 2, 27470 reflections, R = 0.0359.

PMID- 11849060
TI  - A luminescent heterometallic dirhodium-silver chain.
AB  - A novel one-dimensional (1D) heterometallic chain,
      [[Rh(2)(dfpma)(2)(MeCN)(4)](2)[Ag(MeCN)(4)]][PF(6)](5) (1), is afforded from the
      in situ reaction of [ClRh(cod)](2) with [Ag(MeCN)(4)][PF(6)] and dfpma (dfpma =
      bis(difluorophosphine)methylamine). Dichroic crystals, which are obtained from
      MeCN/Et(2)O solutions, crystallize in the monoclinic space group C2/m with a =
      13.570(5) A, b = 20.895(9) A, c = 13.810(6) A, beta = 104.904(7) degrees, V =
      3784(3) A(3), Z = 4. X-ray diffraction studies reveal an asymmetric unit
      comprising two Rh(I)(2) dimers and a square planar Ag(I) cation; this subunit
      propagates to form a 1D heterometallic chain. Compound 1 displays novel
      spectroscopic properties in the solid state, including temperature-dependent
      luminescence.

PMID- 11849061
TI  - Sonochemical preparation of GaSb nanoparticles.
AB  - A room temperature sonochemical method for the preparation of GaSb nanoparticles
      using less hazardous Ga and antimony chloride (SbCl(3)) as the precursors has
      been described. The formation of GaSb has been confirmed by means of XRD, EDAX,
      and XPS characterization. TEM and SAED results show that the as-prepared solid
      consists of nanosized GaSb crystals with sizes in the range 20-30 nm. The
      photoacoustic spectrum result reveals that the GaSb nanoparticles have a direct
      band gap of about 1.21 eV. On the basis of the control experiments and the
      extreme conditions produced by ultrasound, an ultrasound-assisted in-situ
      reduction/combination mechanism has been proposed to explain the reaction.

PMID- 11849062
TI  - Solvothermal synthesis and structure of a new selenium-rich selenophosphate
      K(3)PSe(4).2Se(6).
AB  - The compound K(3)PSe(4).2Se(6) was synthesized at 110 degrees C via
      solventothermal techniques from binary starting materials and Se in acetonitrile.
      The compound crystallizes in the space group Fd macro 3 of the cubic system with
      eight formula units in a cell with a dimension of a = 16.415(2) A at T = 193 K.
      The structure contains an unusual intermixing of ionic and uncharged species. The
      selenophosphate tetrahedral trianions PSe(4)(3-) are surrounded by potassium
      cations; other potassium cations in the structure are coordinated to 12 selenium
      atoms from four Se(6) rings in a tetrahedral arrangement. There are no short
      contacts between adjacent selenium rings. Heating the same reaction mixture to
      160 degrees C results in the formation of only needles of trigonal selenium.

PMID- 11849063
TI  - A half-century of nonclassical organometallic chemistry: a personal perspective.
AB  - A review of some developments in transition metal (nonclassical) organometallic
      chemistry is presented, with emphasis on areas to which the author himself has
      made major and/or seminal contributions: especially fluxional organometallics,
      fluxional metal carbonyls, and the discovery and full explanation of agostic
      hydrogen atoms. An effort has been made to present these topics from the
      perspective of today rather than in strictly chronological order, with a
      sufficient number of specific examples to be concrete, but by no means
      encyclopedic. Particular topics covered are "ring whizzers", concerted shifts of
      two or more CO ligands, twirling M(CO)(3) groups, and merry-go-rounds. In
      addition, the following topics are discussed: the unfinished business of
      mu(2),eta(2),eta(2)-ethene complexes and arene complexes of the lanthanides and
      actinides.

PMID- 11849064
TI  - Unprecedented eta(1)-P(basal) coordination of P(4)X(3) molecules (X = S, Se). An
      experimental and theoretical study of the apical vs basal complexation dichotomy.
AB  - Reaction of [(triphos)Re(CO)(2)(OTf)] (1) [triphos = MeC(CH(2)PPh(2))(3); OTf =
      OSO(2)CF(3)] with P(4)S(3) and P(4)Se(3) yields pairs of coordination isomers,
      namely, [(triphos)Re(CO)(2)[eta(1)-P(apical)-P(4)X(3)]](+) (X = S, 2; Se, 5) and
      [(triphos)Re(CO)(2)[eta(1)-P(basal)-P(4)X(3)]](+) (X = S, 3; Se, 6). The latter
      represent the first examples of the eta(1)-P(basal) coordination achieved by the
      P(4)X(3) molecular cage. Further reaction of 2/3 and 5/6 mixtures with 1 affords
      the dinuclear species [[(triphos)Re(CO)(2)](2)[mu,eta(1:1)-P(apical,)P(basal)
      P(4)X(3)]](2+) (X = S, 4; Se, 7) in which the unprecedented M-eta(1)
      P(basal)/eta(1)-P(apical)-M' bridging coordination of the P(4)X(3) molecule is
      accomplished. A theoretical analysis of the bonding properties of the two
      coordination isomers is also presented. The directionality of apical vs basal
      phosphorus lone pairs is also discussed in terms of MO arguments.

PMID- 11849065
TI  - Triisopropyltriazacyclononane copper(II): an efficient phosphodiester hydrolysis
      catalyst and DNA cleavage agent.
AB  - A 6000-fold rate enhancement has been observed for the hydrolysis of bis(p
      nitrophenyl)phosphate (BNPP) in the presence of 0.2 mM Cu(i-Pr(3)[9]aneN(3))(2+)
      at pH 9.2 and 50 degrees C. In a direct comparison, the rate of hydrolysis of
      BNPP is accelerated at least 60-fold over the previously reported catalyst
      Cu([9]aneN(3))(2+). As observed for Cu([9]aneN(3))(2+), hydrolysis is selective
      for diesters over monoesters. Hydrolysis of BNPP by Cu(i-Pr(3)[9]aneN(3))(2+) is
      catalytic, exhibiting both rate enhancement and turnover. The reaction is
      inhibited by both p-nitrophenyl phosphate and inorganic phosphate. The reaction
      is first-order in substrate and half-order in metal complex, with a k(1.5) of
      0.060 +/- 0.004 M(-1/2) s(-1) at 50 degrees C. The temperature dependence of the
      rate constant results in a calculated activation enthalpy (Delta H(++) of 51 +/-
      2 kJ mol(-1) and activation entropy (Delta S(++)) of -110 +/- 6 J mol(-1) K(-1).
      The kinetic pK(a) of 7.8 +/- 0.2 is close to the thermodynamic pK(a) of 7.9 +/-
      0.2, consistent with deprotonation of a coordinated water molecule in the active
      form of the catalyst. The active catalyst [Cu(i-Pr(3)[9]aneN(3))(OH)(OH(2))](+)
      is in equilibrium with an inactive dimer, and the formation constant for this
      dimer is between 216 and 1394 M(-1) at pH 9.2 and 50 degrees C. Temperature
      dependence of the dimer formation constant K(f) indicates an endothermic enthalpy
      of formation for the dimer of 27 +/- 3 kJ mol(-1). The time course of anaerobic
      DNA cleavage by Cu(i-Pr(3)[9]aneN(3))(2+) is presented over a wide range of
      concentrations at pH 7.8 at 50 degrees C. The concentration dependence of DNA
      cleavage by Cu([9]aneN(3))(2+) and Cu(i-Pr(3)[9]aneN(3))(2+) reveals a maximum
      cleavage efficiency at sub-micromolar concentrations of cleavage agent. DNA
      cleavage by Cu(i-Pr(3)[9]aneN(3))(2+) is twice as efficient at pH 7.8 as at pH
      7.2.

PMID- 11849066
TI  - Control of charge-transfer-induced spin transition temperature on cobalt-iron
      Prussian blue analogues.
AB  - The electronic and spin states of a series of Co-Fe Prussian blue analogues
      containing Na(+) ion in the lattice, Na(x)()Co(y)()Fe(CN)(6) x zH(2)O, strongly
      depended on the atomic composition ratio of Co to Fe (Co/Fe) and temperature.
      Compounds of Co/Fe = 1.5 and 1.15 consisted mostly of the
      Fe(III)(t(2g)(5)e(g)(0), LS, S = 1/2)-CN-Co(II)(t(2g)(5)e(g)(2), HS, S = 3/2)
      site and the Fe(II)(t(2g)(6)e(g)(0), LS, S = 0)-CN-Co(III)(t(2g)(6)e(g)(0), LS, S
      = 0) site, respectively, over the entire temperature region from 5 to 350 K.
      Conversely, compounds of Co/Fe = 1.37, 1.32, and 1.26 showed a change in their
      electronic and spin states depending on the temperature. These compounds
      consisted mainly of the Fe(III)-CN-Co(II) site (HT phase) around room temperature
      but turned to the state consisting mainly of the Fe(II)-CN-Co(III) site (LT
      phase) at low temperatures. This charge-transfer-induced spin transition (CTIST)
      phenomenon occurred reversibly with a large thermal hysteresis of about 40 K. The
      CTIST temperature (T(1/2) = (T(1/2) descending + T(1/2) ascending)/2) increased
      from 200 to 280 K with decreasing Co/Fe from 1.37 to 1.26. Furthermore, by light
      illumination at 5 K, the LT phase of compounds of Co/Fe = 1.37, 1.32, and 1.26
      was converted to the HT phase, and the relaxation temperature from this
      photoproduced HT phase also strongly depended on the Co/Fe ratio; 145 K for Co/Fe
      = 1.37, 125 K for Co/Fe = 1.32, and 110 K for Co/Fe = 1.26. All these phenomena
      are explained by a simple model using potential energy curves of the LT and HT
      phases. The energy difference of two phases is determined by the ligand field
      strength around Co(II) ions, which can be controlled by Co/Fe.

PMID- 11849067
TI  - Synthesis and solution studies of the complexes of trivalent lanthanides with the
      tetraazamacrocycle TETA-(PO)(2).
AB  - A new potentially multidentate hexaprotic ligand H(6)[TETA-(PO)(2)] has been
      prepared by reaction of ethylenediamine-N,N'-diacetic acid (EDDA),
      paraformaldehyde, and phosphinic acid; its coordination properties with three
      lanthanide ions (La(3+), Gd(3+), and Lu(3+)) have been explored. The structures
      of the complexes were studied in aqueous solution by potentiometric pH titrations
      and by (31)P NMR spectroscopy. Four acidity constants were determined
      potentiometrically in the range 2.5 < pH < 14. The four measured pK(a) values can
      be divided into two groups, and within each group the initial deprotonation was
      found to have little effect on the second. Variable temperature (31)P and
      (31)P[(1)H] EXSY NMR spectra showed that, for [Lu(TETA-(PO)(2))](3-), the two
      phosphorus atoms exist in different chemical environments and undergo an exchange
      process which is very fast on the NMR time scale at room temperature. This result
      is consistent with one of the phosphinate residues coordinating the metal ion and
      exchanging with a free analogue. In the case of [La(TETA-(PO)(2))](3-), only one
      temperature invariant signal is observed in (31)P NMR spectra; it corresponds to
      both phosphinate residues remaining uncoordinated to La(3+). The stability of
      [Ln(TETA-(PO)(2))](3-) has an order of La(3+) > Gd(3+) > Lu(3+). The coordination
      of one phosphinate residue to Lu(3+) brings the metal ion closer to the plane of
      four nitrogens and farther from the four carboxylate arms, resulting in [Lu(TETA
      (PO)(2))](3-) having a lower stability than the corresponding La(3+) and Gd(3+)
      complexes. A pM-pH distribution diagram showed that introducing two phosphinate
      groups into TETA renders [Gd(TETA-(PO)(2))](3-) more stable than [Gd(TETA)](-).
      The selectivity factor of the ligand for Gd(3+) vs Ca(2+), Zn(2+), and Cu(2+) has
      been calculated, and the hydration number for [Dy(TETA-(PO)(2))](3-) has been
      measured by (17)O NMR spectroscopy to be zero.

PMID- 11849068
TI  - AsCl(3): from the crystalline to the liquid state. XRD (176 < T (K) < 250) and
      WAXS (295 K) studies.
AB  - This paper presents structural studies on crystalline and liquid AsCl(3),
      performed using X-ray diffraction (XRD) and wide-angle X-ray scattering (WAXS) in
      the 176-250 K temperature range and at 295 K for the crystalline and liquid
      samples, respectively. The XRD results, collected using a single-crystal
      diffractometer, show that AsCl(3) crystallizes in the orthorhombic system with
      P2(1)2(1)2(1) space group and the unit cell parameters a = 9.475(3) A, b =
      11.331(2) A, and c = 4.2964(8) A at 221 K. This structure is stable in the
      temperature range 176-243 K. Above the melting point, at 257 K, transition to the
      liquid state is observed. The WAXS data were recorded up to a maximum scattering
      vector K(max) = 16 A(-1) and then converted to real space by the sine Fourier
      transform, yielding to the reduced radial distribution function (RRDF). For a
      series of models, based on the crystalline AsCl(3) structure, the intensity and
      RRDF functions have been computed and compared with the experimental data. These
      simulations indicate that the model consisting of six AsCl(3) molecules, arranged
      along the y axis, accounts satisfactorily for the experimental observation. The
      results of the structure analysis in both crystalline and liquid states are
      discussed in relation to the influence of the As lone electron pair.

PMID- 11849069
TI  - Oxidative addition of phosphine-tethered thiols to iron carbonyl: binuclear
      phosphinothiolate complexes, (mu-SCH(2)CH(2)PPh(2))(2)Fe(2)(CO)(4), and hydride
      derivatives.
AB  - The mononuclear complex Fe(CO)(4)(PPh(2)CH(2)CH(2)SH), 1, is isolated as an
      intermediate in the overall reaction of PPh(2)CH(2)CH(2)SH with [Fe(0)(CO)(4)]
      sources to produce binuclear bridging thiolate complexes. Photolysis is required
      for loss of CO and subsequent S-H activation to generate the metal-metal bonded
      Fe(I)-Fe(I) complex, (mu-SCH(2)CH(2)PPh(2))(2)Fe(2)(CO)(4), 2. Isomeric forms of
      2 derive from the apical or basal position of the P-donor ligand in the pseudo
      square pyramidal S(2)Fe(CO)(2)P coordination spheres. This position in turn is
      dictated by the stereochemistry of the mu-S-CH(2) bond, designated as syn or anti
      with respect to the Fe(2)S(2) butterfly core. Addition of strong acids engages
      the Fe(I)-Fe(I) bond density as a bridging hydride, [(mu-H)-anti
      2](+)[SO(3)CF(3)](-) or [(mu-H)-syn-2](+)[SO(3)CF(3)](-), with formal oxidation
      to Fe(II)-H-Fe(II). Molecular structures of anti-2, syn-2, and [(mu-H)-anti
      2](+)[SO(3)CF(3)](-) were determined by X-ray crystallography and show
      insignificant differences in distance and angle metric parameters, including the
      Fe-Fe bond distances which average 2.6 A. The lack of coordination sphere
      rearrangements is consistent with the ease with which deprotonation occurs, even
      with the weak base, chloride. The Fe(I)-Fe(I) bond, supported by bridging
      thiolates, therefore presents a site where a proton might be taken up and stored
      as a hydride without impacting the overall structure of the binuclear complex.

PMID- 11849070
TI  - X-ray single-crystal structure and magnetic properties of Fe[CH(3)PO(3))] x
      H(2)O: a layered weak ferromagnet.
AB  - The crystal and molecular structure of the layered weak-ferromagnet
      Fe[CH(3)PO(3)] x H(2)O has been solved by X-ray single-crystal diffraction
      techniques. Crystal data for Fe[CH(3)PO(3)] x H(2)O are the following:
      orthorhombic space group Pna2(1); a =17.538(2), b = 4.814(1), c = 5.719(1) A. The
      structure is lamellar, and it consists of alternating organic and inorganic
      layers along the a direction of the unit cell. The inorganic layers are made of
      Fe(II) ions octahedrally coordinated by five phosphonate oxygen atoms and one
      from oxygen of the water molecule. Each phosphonate group coordinates four metal
      ions, through chelation and bridging, making in this way a cross-linked Fe-O
      network. The resultant layers are then separated by bilayers of the methyl
      groups, with van der Waals contacts between them. The compound is air stable, and
      it dehydrates under inert atmosphere at temperatures above 120 degrees C. The
      oxidation state of the metal ion is +2, and the electronic configuration is d(6)(
      )()high spin (S = 2), as determined from dc magnetic susceptibility measurements
      from 150 K to ambient temperature. Below 100 K, the magnetic moment of
      Fe[CH(3)PO(3)] x H(2)O rises rapidly to a maximum at T(max) approximately equal
      to 24 K, and then it decreases again. The onset of peak at T = 25 K is associated
      with the 3D antiferromagnetic long-range ordering, T(N). The observed critical
      temperature, T(N), is like all the other previously reported Fe(II) phosphonates,
      and it appears to be nearly independent of the interlayer spacing in this family
      of hybrid organic-inorganic layered compounds. Below T(N), the compound behaves
      as a "weak ferromagnet", and represents the third kind of magnetic materials with
      a spontaneous magnetization below a finite critical temperature, ferromagnets and
      ferrimagnets being the other two types.

PMID- 11849071
TI  - Synthesis and structural studies of 1,1'-bis-amino-functionalized ferrocenes,
      ferrocene salts, and ferrocenium salts.
AB  - Having isolated and characterized a series of sodium cyclopentadienide salts, we
      have synthesized a number of 1,1'-bis-amino-functionalized ferrocenes, 1,1'-bis
      amino-functionalized ferrocene salts, and 1,1'-bis-amino-functionalized
      ferrocenium salts. Among these are the first crystallographically characterized
      examples of cyclopentadienyl units containing (piperidin-N-ylethyl)- and (pyrid-2
      ylmethyl)cyclopentadienyl side chains. In the cases of some of the ferrocenes,
      ferrocene salts, and ferrocenium salts, there are some interesting structural
      features in the solid state. These include C-H...N and C-H...pi cloud
      interactions as well as N-H...O and N-H...F hydrogen bonds.

PMID- 11849072
TI  - Carbamoylphosphine oxide complexes of trivalent lanthanide cations: role of
      counterions, ligand binding mode, and protonation investigated by quantum
      mechanical calculations.
AB  - We present a quantum mechanical study of carbamoylphosphine oxide (CMPO)
      complexes of MX(3) (M(3+) = La(3+), Eu(3+), Yb(3+); X(-) = Cl(-), NO(3)(-)) with
      a systematic comparison of monodentate vs bidentate binding modes of CMPO. The
      per ligand interaction energies Delta E increase from La(3+) to Yb(3+) and are
      higher with Cl(-) than with NO(3)(-) as counterions, as a result of steric strain
      in the first coordination sphere with the bidentate anions. The energy difference
      between monodentate (via phosphoryl oxygen) and bidentate CMPO complexes is
      surprisingly small, compared to Delta E or to the binding energy of one solvent
      molecule. Protonation of uncomplexed CMPO takes place preferably at the
      phosphoryl oxygen O(P), while in the Eu(NO(3))(3)CMPOH(+) complex carbonyl (O(C))
      protonation is preferred and O(P) is bonded to the metal. A comparison of uranyl
      and lanthanide nitrate complexes of CMPO shows that the interaction energies
      Delta E of the former are lower. Finally, the effect of grafting CMPO arms at the
      wide rim of a calix[4]arene platform is described. The results are important for
      our understanding of cation binding and extraction by potentially bidentate CMPO,
      diamide, and diphosphoryl types of ligands.

PMID- 11849073
TI  - Ring, chain, and cluster compounds in the Cl-Ga-N-H system.
AB  - The formation of gas-phase oligomer compounds in the Cl-Ga-N-H system is
      considered using hybrid Hartree-Fock/density functional theory and a polarized
      double-zeta quality basis set. Geometric parameters, vibrational frequencies, and
      thermodynamic characteristics for the Cl(3)GaNH(3) adduct, its dissociation
      products GaCl(n), NH(n), (n= 1-3), the amidochlorogallanes [Cl(2)GaNH(2)](n) (n =
      1-3), their donor-acceptor complexes with GaCl(3) and NH(3), and the
      imidochlorogallanes [ClGaNH](n) (n = 1-4,6) have been obtained. Generation of
      amidochlorogallanes is expected to be viable during laser assisted chemical vapor
      deposition (CVD) at low temperatures. High-temperature association processes in
      the gas phase during the CVD of GaN from the Cl(3)GaNH(3) adduct are predicted to
      be less important, in contrast to previous findings for the aluminum analogue.
      This difference may be explained in terms of a much lower Ga-N bond energy
      compared to Al-N in the ring and cluster compounds.

PMID- 11849074
TI  - (29)Si NMR shifts and relative stabilities calculated for hypercoordinated
      silicon-polyalcohol complexes: role in sol-gel and biogenic silica synthesis.
AB  - Penta- and hexa-coordinated silicon is rare, occurring as a transient species in
      some glasses, nonaqueous organosilicon solutions and organosilicon gels such as
      silicone, and is stable at high pressures within the earth in dense phases such
      as stishovite. The stable form expected in aqueous solution is quadra-coordinated
      silicon. A recent study proposed the existence of hypercoordinated silicon
      polyalcohol complexes in aqueous solution, based on (29)Si NMR shifts at -102 to 
      103 ppm and -145 to -147 ppm. Here, we report ab initio molecular orbital
      calculations of (29)Si NMR chemical shifts and relative stabilities of silicon
      polyalcohol monocyclic and spirocyclic complexes, from ethylene glycol
      (C(2)H(6)O(2)) to arabitol (C(5)H(12)O(5)) with Si in quadra-, penta- and hexa
      coordination ((Q)Si, (P)Si, (H)Si), calculated at the HF/6-311+G(2d,p)//HF/6-31G*
      level. Calculated shifts are accurate with a 1-8% error for (Q)Si and 2-9% for
      (P)Si. Shifts calculated for the hypercoordinated silicon complexes having
      structures proposed in the literature are much more negative (-128 and -180 ppm
      for (P)Si and (H)Si) than observed. We propose that cyclic trimers complexed by
      polyalcohols can explain the -102 ppm shift, where the Si atoms are all (Q)Si, or
      where two silicons are (Q)Si and one is (P)Si with rapid exchange between the Si
      sites. The -145 ppm resonance results from structures similar to those proposed
      in the experimental NMR study for the -102 ppm peak. Our relative stability
      calculations indicate that structures proposed in the literature for
      hypercoordinated silicon complexes are thermodynamically unstable in aqueous
      solution at acidic to neutral conditions but may exist in degrading silicone-gel
      breast-implants. Thus, aqueous hypercoordinated silicon-polyalcohol complexes are
      unlikely to play an important role in biological silicon uptake and hold little
      promise for novel silica synthesis routes from aqueous solutions under nonextreme
      conditions.

PMID- 11849075
TI  - Cation-independent electron transfer between ferricyanide and ferrocyanide ions
      in aqueous solution.
AB  - Electron transfer between Fe(CN)(6)(3-) and Fe(CN)(6)(4-) in homogeneous aqueous
      solution with K(+) as the counterion normally proceeds almost exclusively by a
      K(+)-catalyzed pathway, but this can be suppressed, and the direct Fe(CN)(6)(3)(
      )-Fe(CN)(6)(4-) electron transfer path exposed, by complexing the K(+) with crypt
      2.2.2 or 18-crown-6. Fe((13)CN)(6)(4-)-NMR line broadening measurements using
      either crypt-2.2.2 or (with extrapolation to zero uncomplexed [K(+)]) 18-crown-6
      gave consistent values for the rate constant and activation volume (k(0) = (2.4
      +/- 0.1) x 10(2) L mol(-1) s(-1) and Delta V(0) = -11.3 +/- 0.3 cm(3) mol(-1),
      respectively, at 25 degrees C and ionic strength I = 0.2 mol L(-1)) for the
      uncatalyzed electron transfer path. These values conform well to predictions
      based on Marcus theory. When [K(+)] was controlled with 18-crown-6, the observed
      rate constant k(ex) was a linear function of uncomplexed [K(+)], giving k(K) =
      (4.3 +/- 0.1) x 10(4) L(2) mol(-2) s(-1) at 25 degrees C and I = 0.26 mol L(-1)
      for the K(+)-catalyzed pathway. When no complexing agent was present, k(ex) was
      roughly proportional to [K(+)](total), but the corresponding rate constant k(K)'
      (=k(ex)/[K(+)](total)) was about 60% larger than k(K), evidently because ion
      pairing by hydrated K(+) lowered the anion-anion repulsions. Ionic strength as
      such had only a small effect on k(0), k(K), and k(K)'. The rate constants
      commonly cited in the literature for the Fe(CN)(6)(3-/4-) self-exchange reaction
      are in fact k(K)'[K(+)](total) values for typical experimental [K(+)](total)
      levels.

PMID- 11849076
TI  - Redox induced reversible structural transformations of dimeric and polymeric
      phenanthroline-based copper chelates.
AB  - The synthesis and characterization of copper complexes of the phenanthroline
      based bridging ligands, 9-methyl-2-(2-[4-[2-(9-methyl-1,10-phenanthrolin-2
      yl)ethyl]phenyl]ethyl)-1,10-phenanthroline, 1, and 1,12-bis(9-methyl-1,10
      phenanthroline-2-yl)dodecane, 2, are presented. Whereas in the first case a
      discrete dimeric complex [Cu(2)(1)(2)](BF(4))(2) was formed, in the latter, a
      coordination polymer [2(Cu(2))(n)](BF(4))(n) resulted. Both of these materials
      have been characterized by cyclic voltammetry (CV), the electrochemical quartz
      crystal microbalance (EQCM), and UV-vis spectroscopy and the results compared to
      those of the monomeric [Cu(dmp)(2)](BF(4)) (dmp is 2,9-dimethyl-1,10
      phenanthroline) species. Oxidation of the dimeric species results in its
      precipitation and reduction results in stripping of the deposited layer as
      ascertained from CV and EQCM measurements. The electrooxidation of the copper
      centers in the coordination polymer results in changes in the coordination which
      are fully reversible upon reduction. The dissociation/regeneration of the
      coordination polymer as a function of the redox state of the copper centers has
      been characterized by CV, EQCM, and UV-vis spectroelectrochemistry.

PMID- 11849077
TI  - Donor properties of the vanadyl ion: reactions of vanadyl salicylaldimine beta
      ketimine and acetylacetonato complexes with groups 14 and 15 Lewis acids.
AB  - Reactions of organosilicon, -germanium, -tin, -lead, -antimony, and -tin
      tetrahalide Lewis acids with VO(salen) [H(2)salen = N,N'-bis(salicylidene)ethane
      1,2-diamine], related vanadyl salicylaldimines, VO(acacen) [H(2)acacen = N,N'
      bis(acetylacetonato)ethane-1,2-diamine], and VO(acac)(2) (acac = acetylacetonato)
      have been investigated, revealing VO(salen) and VO(acacen) to be significantly
      stronger vanadyl donors than VO(acac)(2). The vanadyl donor strength of VO(salen)
      significantly diminishes with the introduction of electron-withdrawing
      substituents on the salicylaldimine ligand, and the introduction of methyl
      substituents on the imine carbon atoms can result in a preference for phenolic
      over vanadyl oxygen donation. Vanadyl donation results in an increase in the
      vanadyl bond length, while it leaves the distance of vanadium from the basal
      plane relatively unaffected. Coordination of water trans to a vanadyl oxygen that
      is involved in a donor bond to tin or lead has little or no effect on the vanadyl
      bond length but results in a marked movement of vanadium toward the basal plane
      and a decrease of the V=O-D (D = Sn or Pb) bond angle by as much as 13 degrees,
      the latter reflecting a loss of multiple bond character of the vanadyl bond.
      Formation of a vanadyl donor bond results in a decrease in both the vanadyl
      stretching frequency (infrared spectrum) and energy of the e(pi) <-- b(2)
      transition (electronic spectrum), the latter being intimately related to the
      strength of the vanadyl donor bond, while the shift of the b(1) <-- b(2)
      transition to higher or lower energy is relatively small for vanadyl
      salicylaldimine and beta-ketimine complexes. Donation through the phenolic oxygen
      atoms results in an increase in the vanadyl stretching frequency and energy of
      the e(pi) <-- b(2) transition, which can result in e(pi) <-- b(2)/b(1) <-- b(2)
      energy crossover.

PMID- 11849078
TI  - Synthesis and characterization of iron(III)-substituted, dimeric
      polyoxotungstates, [Fe(4)(H(2)O)(10)(beta-XW(9)O(33))(2)](n-) (n = 6, X =
      As(III), Sb(III); n = 4, X = Se(IV), Te(IV)).
AB  - Interaction of the lacunary [alpha-XW(9)O(33)](9-) (X = As(III), Sb(III)) with
      Fe(3+) ions in acidic, aqueous medium leads to the formation of dimeric
      polyoxoanions, [Fe(4)(H(2)O)(10)(beta-XW(9)O(33))(2)](6-) (X = As(III), Sb(III))
      in high yield. X-ray single-crystal analyses were carried out on
      Na(6)[Fe(4)(H(2)O)(10)(beta-AsW(9)O(33))(2)] x 32H(2)O, which crystallizes in the
      monoclinic system, space group C2/m, with a = 20.2493(18) A, b = 15.2678(13) A, c
      = 16.0689(14) A, beta = 95.766(2) degrees, and Z = 2; Na(6)[Fe(4)(H(2)O)(10)(beta
      SbW(9)O(33))(2)] x 32H(2)O is isomorphous with a = 20.1542(18) A, b = 15.2204(13)
      A, c = 16.1469(14) A, and beta = 95.795(2) degrees. The selenium and tellurium
      analogues are also reported, [Fe(4)(H(2)O)(10)(beta-XW(9)O(33))(2)](4-) (X =
      Se(IV), Te(IV)). They are synthesized from sodium tungstate and a source of the
      heteroatom as precursors. X-ray single-crystal analysis was carried out on
      Cs(4)[Fe(4)(H(2)O)(10)(beta-SeW(9)O(33))(2)] x 21H(2)O, which crystallizes in the
      triclinic system, space group P macro 1, with a = 12.6648(10) A, b = 12.8247(10)
      A, c = 16.1588(13) A, alpha = 75.6540(10) degrees, beta = 87.9550(10) degrees,
      gamma = 64.3610(10) gamma, and Z = 1. All title polyanions consist of two (beta
      XW(9)O(33)) units joined by a central pair and a peripheral pair of Fe(3+) ions
      leading to a structure with idealized C(2h) symmetry. It was also possible to
      synthesize the Cr(III) derivatives [Cr(4)(H(2)O)(10)(beta-XW(9)O(33))(2)](6-) (X
      = As(III), Sb(III)), the tungstoselenates(IV) [M(4)(H(2)O)(10)(beta
      SeW(9)O(33))(2)]((16)(-)(4n)-) (M(n+) = Cr(3+), Mn(2+), Co(2+), Ni(2+), Zn(2+),
      Cd(2+), and Hg(2+)), and the tungstotellurates(IV) [M(4)(H(2)O)(10)(beta
      TeW(9)O(33))(2)]((16-4n)-) (M(n+) = Cr(3+), Mn(2+), Co(2+), Ni(2+), Cu(2+),
      Zn(2+), Cd(2+), and Hg(2+)), as determined by FTIR. The electrochemical
      properties of the iron-containing species were also studied. Cyclic voltammetry
      and controlled potential coulometry aided in distinguishing between Fe(3+) and
      W(6+) waves. By variation of pH and scan rate, it was possible to observe the
      stepwise reduction of the Fe(3+) centers.

PMID- 11849079
TI  - o-Iminobenzosemiquinonato complexes of Mn(III) and Mn(IV). Synthesis and
      characterization of [Mn(III)(L(ISQ))(2)(L(AP))] (S(t) = 1) and
      [Mn(IV)(L(ISQ))(2)(L(AP)-H)] (S(t) = 1/2).
AB  - From the reaction of [Mn(III)(3)(micro-O)(micro-CH(3)CO(2))(6)]CH(3)CO(2)
      (manganese(III) acetate) and 2-anilino-4,6-di-tert-butylphenol (1:3) in methanol
      under anaerobic conditions, dark brown-black crystals of
      [Mn(III)(L(ISQ))(2)(L(AP))] (1) were obtained in approximately 30% yield.
      (L(AP))(-) represents the closed-shell o-aminophenolate(-) form of the above
      ligand, and (L(ISQ))(-) is the monoanionic pi radical form o
      iminobenzosemiquinonate(-) (S(rad) = 1/2). Complex 1 can be deprotonated at the
      (L(AP))(-) ligand and one-electron-oxidized by air, yielding crystals of
      [Mn(IV)(L(ISQ))(2)(L(AP)-H)] (2), where (L(AP)-H)(2-) represents the closed
      shell, dianionic o-amidophenolate(2-) form of the above ligand. The structures of
      1 and 2 have been determined by X-ray crystallography at 100 K. The protonation
      and oxidation levels of the ligands and of the metal ions have been unequivocally
      established: both complexes contain two pi radical ligands, 1 contains a Mn(III)
      ion, and 2 contains a Mn(IV) ion. The spins of the radicals (S(rad) = 1/2) couple
      strongly antiferromagnetically with the d(4) and d(3) configuration of the Mn
      ions in 1 and 2, respectively, yielding the observed ground states of S = 1 for 1
      and S = (1)/(2) for 2. This has been established by temperature-dependent
      susceptibility measurements (2-300 K) and S- and X-band EPR spectroscopy.

PMID- 11849080
TI  - Electronic structures of electron-rich octahedrally condensed transition-metal
      chalcogenide clusters.
AB  - The electronic structures of some electron-rich octahedrally condensed transition
      metal chalcogenide clusters are analyzed with the aid of extended Huckel and
      density functional molecular orbital calculations. A simple orbital approach is
      developed to analyze the electron counts of these clusters, which do not obey any
      existing electron-counting rules. Different electron counts are allowed,
      depending upon the nature of the metal. Optimal counts are discussed. Metal-metal
      bonding is generally weak in these species. Consequently, their structural
      arrangements are mainly governed by metal-ligand interactions.

PMID- 11849081
TI  - Bridging nitrate groups in [Mn(4)O(3)(NO(3))(O(2)CMe)(3)(R(2)dbm)(3)] (R = H, Et)
      and [Mn(4)O(2)(NO(3))(O(2)CEt)(6)(bpy)(2)](ClO(4)): acidolysis routes to
      tetranuclear manganese carboxylate complexes.
AB  - New synthesis procedures are described to tetranuclear manganese carboxylate
      complexes containing the [Mn(4)O(2)](8+) or [Mn(4)O(3)X](6+) (X(-) = MeCO(2)(-),
      F(-), Cl(-), Br(-), NO(3)(-)) core. These involve acidolysis reactions of
      [Mn(4)O(3)(O(2)CMe)(4)(dbm)(3)] (1; dbm is the anion of dibenzoylmethane) or
      [Mn(4)O(2)(O(2)CEt)(6)(dbm)(2)] (8) with HX (X(-) = F(-), Cl(-), Br(-), NO(3)(
      )); high-yield routes to 1 and 8 are also described. The X(-) = NO(3)(-)
      complexes [Mn(4)O(3)(NO(3))(O(2)CR)(3)(R'(2)dbm)(3)] (R = Me, R' = H (6); R = Me,
      R' = Et (7); R = Et, R' = H (12)) represent the first synthesis of the
      [Mn(4)O(3)(NO(3))](6+) core, which contains an unusual eta(1):mu(3)-NO(3)(-)
      group. Treatment of known [Mn(4)O(2)(O(2)CEt)(7)(bpy)(2)](ClO(4)) with HNO(3)
      gives [Mn(4)O(2)(NO(3))(O(2)CEt)(6)(bpy)(2)](ClO(4)) (15) containing a
      eta(1):eta(1):mu-NO(3)(-) group bridging the two body Mn(III) ions of the
      [Mn(4)O(2)](8+) butterfly core. Complex 7 x 4CH(2)Cl(2) crystallizes in space
      group P2(1)2(1)2(1) with (at -168 degrees C) a = 21.110(3) A, b = 22.183(3) A, c
      = 15.958(2) A, Z = 4, and V = 7472.4(3) A(3). Complex 15 x (3)/(2)CH(2)Cl(2)
      crystallizes in space group P2(1)/c with (at -165 degrees C) a = 26.025(4) A, b =
      13.488(2) A, c = 32.102(6) A, beta = 97.27(1) degrees, Z = 8, and V = 11178(5)
      A(3). Complex 7 contains a [Mn(4)(mu(3)-O)(3)(mu(3)-NO(3))](6+) core (3Mn(III),
      Mn(IV)) as seen for previous [Mn(4)O(3)X](6+) complexes. Complex 15 contains a
      butterfly [Mn(4)(mu(3)-O)(2)](8+) core. (1)H NMR spectra have been recorded for
      all complexes reported in this work and the various resonances assigned. All
      complexes retain their structural integrity on dissolution in chloroform and
      dichloromethane. Magnetic susceptibility (chi(M)) data were collected on 12 in
      the 5-300 K range in a 10.0 kG (1 T) field. Fitting of the data to the
      theoretical chi(M) vs T expression appropriate for a [Mn(4)O(3)X](6+) complex of
      C(3)(v)() symmetry gave J(34) = -23.9 cm(-)(1), J(33) = 4.9 cm(-)(1), and g =
      1.98, where J(34) and J(33) refer to the Mn(III)Mn(IV) and Mn(III)Mn(III)
      pairwise exchange interactions, respectively. The ground state of the molecule is
      S = 9/2, as found previously for other [Mn(4)O(3)X](6+) complexes. This was
      confirmed by magnetization data collected at various fields and temperatures.
      Fitting of the data gave S = 9/2, D = -0.45 cm(-1), and g = 1.96, where D is the
      axial zero-field splitting parameter.

PMID- 11849082
TI  - [Fe(bipy)(CN)(4)](-) as a versatile building block for the design of
      heterometallic systems: synthesis, crystal structure, and magnetic properties of
      PPh(4)[Fe(III)(bipy)(CN)(4)] x H(2)O, [[Fe(III)(bipy)(CN)(4)](2)M(II)(H(2)O)(4)]
      x 4H(2)O, and [[Fe(III)(bipy)(CN)(4)](2)Zn(II)] x 2H(2)O [bipy = 2,2'-Bipyridine;
      M = Mn and Zn].
AB  - The new cyano complexes of formulas PPh(4)[Fe(III)(bipy)(CN)(4)] x H(2)O (1),
      [[Fe(III)(bipy)(CN)(4)](2)M(II)(H(2)O)(4)] x 4H(2)O with M = Mn (2) and Zn (3),
      and [[Fe(III)(bipy)(CN)(4)](2)Zn(II)] x 2H(2)O (4) [bipy = 2,2'-bipyridine and
      PPh(4) = tetraphenylphosphonium cation] have been synthesized and structurally
      characterized. The structure of complex 1 is made up of mononuclear
      [Fe(bipy)(CN)(4)](-) anions, tetraphenyphosphonium cations, and water molecules
      of crystallization. The iron(III) is hexacoordinated with two nitrogen atoms of a
      chelating bipy and four carbon atoms of four terminal cyanide groups, building a
      distorted octahedron around the metal atom. The structure of complexes 2 and 3
      consists of neutral centrosymmetric [[Fe(III)(bipy)(CN)(4)](2)M(II)(H(2)O)(4)]
      heterotrinuclear units and crystallization water molecules. The
      [Fe(bipy)(CN)(4)](-) entity of 1 is present in 2 and 3 acting as a monodentate
      ligand toward M(H(2)O)(4) units [M = Mn(II) (2) and Zn(II) (3)] through one
      cyanide group, the other three cyanides remaining terminal. Four water molecules
      and two cyanide nitrogen atoms from two [Fe(bipy)(CN)(4)](-) units in trans
      positions build a distorted octahedron surrounding Mn(II) (2) and Zn(II) (3). The
      structure of the [Fe(phen)(CN)(4)](-) complex ligand in 2 and 3 is close to that
      of the one in 1. The intramolecular Fe-M distances are 5.126(1) and 5.018(1) A in
      2 and 3, respectively. 4 exhibits a neutral one-dimensional polymeric structure
      containing two types of [Fe(bipy)(CN)(4)](-) units acting as bismonodentate
      (Fe(1)) and trismonodentate (Fe(2)) ligands versus the divalent zinc cations
      through two cis-cyanide (Fe(1)) and three fac-cyanide (Fe(2)) groups. The
      environment of the iron atoms in 4 is distorted octahedral as in 1-3, whereas the
      zinc atom is pentacoordinated with five cyanide nitrogen atoms, describing a very
      distorted square pyramid. The iron-zinc separations across the single bridging
      cyanides are 5.013(1) and 5.142(1) A at Fe(1) and 5.028(1), 5.076(1), and
      5.176(1) A at Fe(2). The magnetic properties of 1-3 have been investigated in the
      temperature range 2.0-300 K. 1 is a low-spin iron(III) complex with an important
      orbital contribution. The magnetic properties of 3 correspond to the sum of two
      magnetically isolated spin triplets, the antiferromagnetic coupling between the
      low-spin iron(III) centers through the -CN-Zn-NC- bridging skeleton (iron-iron
      separation larger than 10 A) being very weak. More interestingly, 2 exhibits a
      significant intramolecular antiferromagnetic interaction between the central spin
      sextet and peripheral spin doublets, leading to a low-lying spin quartet.

PMID- 11849084
TI  - Cation control of pore and channel size in cage-based metal-organic porous
      materials.
AB  - Porous materials resembling zeolites that are composed of organic and inorganic
      building units were synthesized and characterized. Control of pore and channel
      size was achieved by using different-sized cations. The metal-assembled, anionic
      cage molecule, Co(4)1(2)(8-), with a hydrophobic cavity and four carboxylate rich
      arms, was used as a structural unit for the formation of materials with pores and
      channels. When assembled into a solid material with dications (Mg(2+), Ca(2+),
      Sr(2+), and Ba(2+)), Co(4)1(2)(8-) arranges into sheets of cages linked together
      by cations. The series of materials based on Co(4)1(2)(8-) and containing
      alkaline earth cations was characterized using X-ray crystallography. The
      magnesium material packs with cages close together, has small channels, and has
      cation-carboxylate linkages in three dimensions. The calcium material has cages
      packed with voids between them and has 5 x 10 A channels and 10 x 21 A pores. The
      strontium and barium materials also pack with voids between the cages and
      similarly to each other. They have 11 x 13 A and 11 x 11 A channels and 10 x 27 A
      and 9 x 27 A pores, respectively. Each of these materials has many (20-50)
      solvent water molecules associated with each cage. The associated water can be
      removed from and adsorbed by the materials. The heat of water binding has been
      measured to be -52 kJ/mol (Mg(4)Co(4)1(2)); -47 kJ/mol (Ca(4)Co(4)1(2)); -48
      kJ/mol (Sr(4)Co(4)1(2)); -49 kJ/mol (Ba(4)Co(4)1(2)).

PMID- 11849083
TI  - Synthetic analogue of the [Fe(2)(mu-OH)(2)(mu-O(2)CR)](3+) core of soluble
      methane monooxygenase hydroxylase via synthesis and dioxygen reactivity of
      carboxylate-bridged diiron(II) complexes.
AB  - We describe the synthesis and dioxygen reactivity of diiron(II) tetracarboxylate
      complexes [Fe(2)(mu-O(2)CAr(Tol))(2)(O(2)CAr(Tol))(2)(N,N-Me(2)en)(2)] (2) and
      [Fe(2)(mu-O(2)CAr(Tol))(2)(O(2)CAr(Tol))(2)(N,N-Bn(2)en)(2)] (6), where
      Ar(Tol)CO(2)(-) = 2,6-di(p-tolyl)benzoate. These complexes were prepared as
      models for the diiron(II) center in the hydroxylase component of soluble methane
      monooxygenase (MMOH). Compound 6 reacts with dioxygen to afford PhCHO in
      approximately 60(5)% yield, following oxidative N-dealkylation of the pendant
      benzyl group on the diamine ligand. The diiron(III) complex [Fe(2)(mu-OH)(2)(mu
      O(2)CAr(Tol))(O(2)CAr(Tol))(3)(N-Bnen)(N,N-Bn(2)en)] (8) was isolated from the
      reaction mixture. The 4.2 K Mossbauer spectrum of 8 displays a single quadrupole
      doublet with parameters delta = 0.48(2) mm s(-1) and Delta E(Q) = 0.61(2) mm s(
      1). The [Fe(2)(mu-OH)(2)(mu-O(2)CR)](3+) core structure in 8 matches that of the
      fully oxidized form of MMOH. The conversion of 6 to 8 closely parallels the
      chemistry of MMOH in which an O(2)-derived oxygen atom is inserted into the C-H
      bond of methane. Several reaction pathways are considered to account for this
      novel chemical transformation, and these are compared with mechanistic frameworks
      previously developed for related cytochrome P450 and copper(I) dioxygen
      chemistry.

PMID- 11849085
TI  - Bis[(2-diphenylphosphino)phenyl]mercury: a P-donor ligand and precursor to mixed
      metal-mercury (d(8)-d(10)) cyclometalated complexes containing 2-C(6)H(4)PPh(2).
AB  - Treatment of HgCl(2) with 2-LiC(6)H(4)PPh(2) gives [Hg(2-C(6)H(4)PPh(2))(2)] (1),
      whose phosphorus atoms take up oxygen, sulfur, and borane to give the compounds
      [Hg[2-C(6)H(4)P(X)Ph(2)](2)] [ X = O (3), S (4), and BH(3) (5)], respectively.
      Compound 1 functions as a bidentate ligand of wide, variable bite angle that can
      span either cis or trans coordination sites in a planar complex. Representative
      complexes include [HgX(2) x 1] [X = Cl (6a), Br (6b)], cis-[PtX(2) x 1] [X = Cl
      (cis-7), Me (9), Ph (10)], and trans-[MX(2) x 1] [X = Cl, M = Pt (trans-7), Pd
      (8), Ni (11); X = NCS, M = Ni (13)] in which the central metal ions are in either
      tetrahedral (6a,b) or planar (7-11, 13) coordination. The trans disposition of 1
      in complexes trans-7, 8, and 11 imposes close metal-mercury contacts [2.8339(7),
      2.8797(8), and 2.756(8) A, respectively] that are suggestive of a donor-acceptor
      interaction, M --> Hg. Prolonged heating of 1 with [PtCl(2)(cod)] gives the
      binuclear cyclometalated complex [(eta(2)-2-C(6)H(4)PPh(2))Pt(mu-2
      C(6)H(4)PPh(2))(2)HgCl] (14) from which the salt [(eta(2)-2-C(6)H(4)PPh(2))Pt(mu
      2-C(6)H(4)PPh(2))(2)Hg]PF(6) (15) is derived by treatment with AgPF(6). In 14 and
      15, the mu-C(6)H(4)PPh(2) groups adopt a head-to-tail arrangement, and the Pt-Hg
      separation in 14, 3.1335(5) A, is in the range expected for a weak metallophilic
      interaction. A similar arrangement of bridging groups is found in
      [Cl((n)Bu(3)P)Pd(mu-C(6)H(4)PPh(2))(2)HgCl] (16), which is formed by heating 1
      with [PdCl(2)(P(n)()Bu(3))(2)]. Reaction of 1 with [Pd(dba)(2)] [dba =
      dibenzylideneacetone] at room temperature gives [Pd(1)(2)] (19) which, in air,
      forms a trigonal planar palladium(0) complex 20 containing bidentate 1 and the
      monodentate phosphine-phosphine oxide ligand [Hg(2-C(6)H(4)PPh(2))[2
      C(6)H(4)P(O)Ph(2)]]. On heating, 19 eliminates Pd and Hg, and the C-C coupled
      product 2-Ph(2)PC(6)H(4)C(6)H(4)PPh(2)-2 (18) is formed by reductive elimination.
      In contrast, 1 reacts with platinum(0) complexes to give a bis(aryl)platinum(II)
      species formulated as [Pt(eta(1)-C-2-C(6)H(4)PPh(2))(eta(2)-2
      C(6)H(4)PPh(2))(eta(1)-P-1)]. Crystal data are as follows. Compound 3:
      monoclinic, P2(1)/n, with a = 11.331(3) A, b = 9.381(2) A, c = 14.516 A, beta =
      98.30(2) degrees, and Z = 2. Compound 6b x 2CH(2)Cl(2): triclinic, P macro 1,
      with a = 12.720(3) A, b = 13.154(3) A, c = 12.724(2) A, alpha = 92.01(2) degrees,
      beta = 109.19(2) degrees, gamma = 90.82(2) degrees, and Z = 2. Compound trans-7 x
      2CH(2)Cl(2): orthorhombic, Pbca, with a = 19.805(3) A, b = 8.532(4) A, c =
      23.076(2) A, and Z = 4. Compound 11 x 2CH(2)Cl(2): orthorhombic, Pbca, with a =
      19.455(3) A, b = 8.496(5) A, c = 22.858(3) A, and Z = 4. Compound 14: monoclinic,
      P2(1)/c, with a = 13.150(3) A, b = 12.912(6) A, c = 26.724(2) A, beta = 94.09(1)
      degrees, and Z = 4. Compound 20 x C(6)H(5)CH(3).0.5CH(2)Cl(2): triclinic, P macro
      1, with a = 13.199(1) A, b = 15.273(2) A, c = 17.850(1) A, alpha = 93.830(7),
      beta = 93.664(6), gamma = 104.378(7) degrees, and Z = 2.

PMID- 11849086
TI  - Optical investigations of alkali metal thiomanganates(II) containing isolated
      complexes as well as chain and planar compounds.
AB  - Tetracoordinated Mn(II) complexes providing different molecular structures were
      investigated using various spectroscopical procedures. Na(6)MnS(4) contains
      separate pseudotetrahedral Mn-S complex units, K(2)MnS(2) has chains of edge
      shared tetrahedra, and Cs(2)Mn(3)S(4) crystallizes in corresponding layers. Also
      doped materials, i.e., Cs(2)(Mn(x)Zn(1-x))(3)S(4) with 0.0 < x < 1.0, are
      considered. Absorption spectra recorded from samples incorporated in polyethylene
      pellets and excitation spectra taken from pure materials at 15-20 K temperature
      are assigned on the basis of energy level calculations obtained from the angular
      overlap model. All compounds exhibit intensive emission in the red, some of them
      also in the yellow region, which both are investigated in the temperature range
      from 12.5 to 250 K, in some cases varying the excitation power and excitation
      wavelength. Decay measurements supply lifetimes and activation energies evaluated
      from Arrhenius plots. The results support an assignment of both types of
      emissions to MnS(4) complex entities for all compounds, the red emission from the
      lowest excited level (Kasha luminescence) and the yellow emission, observed for
      some of the compounds with increasing intensity at lower temperature, from higher
      electronic levels.

PMID- 11849087
TI  - Formation of molecular ladder elements with macrocyclic platforms via linear
      bifunctional ligands.
AB  - Reaction between 4-aminopyridine and a dinuclear zinc(II) component of a Robson
      macrocyclic ligand has resulted in the formation of a molecular ladder element
      motif. X-ray single crystal structural analysis indicates that two pyridine rings
      are assembled at the same direction of the macrocycle, which are placed in a
      nearly parallel way via pi-pi interactions, forming a concavity structure with a
      macrocyclic base. It is significantly noted that one hydrogen-bond cycle
      generated from hydrogen atoms of two amino groups with two perchlorate anions has
      sustained such an assembly of two 4-aminopyridine species to stand in a face to
      face pattern through a weak molecular interaction on the macrocyclic platform by
      one-end coordination bonding. The self-assembly of 4-carboxylic pyridine acid and
      the same macrocyclic component in the presence of sodium hydroxide has yielded an
      interesting wheel-like complex. Two macrocyclic dinuclear zinc(II) components
      have been linked through coordination bonding with two pyridine derivatives
      situated on the same direction of a macrocycle. X-ray structural results suggest
      that the compound has a unique sandwich-like structure consisting of two
      macrocyclic covers with two inversely positioned bridging pyridine carboxylic
      groups in the middle.

PMID- 11849088
TI  - Structure-directing coordination template effect of ethylenediamine in formations
      of ZnS and ZnSe nanocrystallites via solvothermal route.
AB  - ZnS and ZnSe precursors (ZnS x 0.5en and ZnSe x 0.5en, en = ethylenediamine) were
      prepared via a solvothermal process using ethylenediamine as solvent. Phase-pure
      hexagonal wurtzite ZnS and ZnSe products were obtained by annealing the
      precursors in argon stream at temperatures above 350 degrees C. The role of
      ethylenediamine as a structure-directing coordination molecular template
      responsible for the morphologies of the annealed products was discussed. This
      work provided further insights into the solvent coordination molecular template
      (SCMT) mechanism previously proposed to explain the growth mechanism of CdE (E =
      S, Se, Te) nanorods in ethylenediamine (Inorg. Chem. 1999, 38, 1382). The as
      prepared precursors as well as the annealed products were characterized by powder
      X-ray diffraction (XRD), transmission electron microscopy (TEM), infrared
      absorbance spectroscopy (IR), thermogravimetric analysis (TGA), X-ray
      fluorescence (XRF) analysis, and combustion analysis for C, N, H contents.

PMID- 11849089
TI  - Photochemistry and photophysics of Cr(III) macrocyclic complexes.
AB  - The phosphorescence and photochemical behavior of the macrocyclic complexes
      (1,4,7,10,13,16-hexaazacyclooctadecane)chromium(III) (Cr([18]-aneN(6))(3+); 1)
      and (4,4',4''-ethylidynetris(3-azabutan-1-amine)) chromium(III) (Cr(sen)(3+); 2)
      have been compared to each other and to the complex Cr(en)(3)(3+). For both
      macrocyclic complexes, phosphorescence from room temperature aqueous solutions is
      too weak to be observed, contrasting with Cr(en)(3)(3+), though both had somewhat
      longer 77 K lifetimes than Cr(en)(3)(3+). Phosphorescence lifetimes for these
      macrocyclics decreased with increasing temperature much faster than for
      Cr(en)(3)(3+) and a conventional extrapolation based on a fit of reciprocal
      lifetimes (corrected for the low-temperature contribution) to the Arrhenius
      equation gave estimated room temperature phosphorescence lifetimes of a few
      nanoseconds, consistent with the failure to observe room temperature emission.
      Fitting of the nonlinearity of the data seen in these plots suggested that two
      high-temperature processes were occurring with estimated activation parameters (E
      in kJ mol(-1) and A in s(-1)) for Cr([18]-aneN(6))(3+): E(1) = 40, A(1) = 1 x
      10(16); E(2) = 24, A(2) = 1 x 10(14): Cr(sen)(3+); E(1) = 45, A(1) = 2 x 10(15);
      E(2) = 29, A(2) = 7 x 10(11). Cr([18]-aneN(6))(3+) was photochemically inert on
      irradiation. On irradiation into the lowest quartet ligand field absorption band,
      Cr(sen)(3+) photolyzes with a quantum yield of 0.098 +/- 0.001 at room
      temperature. Laser flash photolysis with conductivity detection showed that this
      photoreaction occurred faster than protonation of the liberated amine ligand at
      all practical proton concentrations. The quantum yield for irradiation directly
      into the doublet absorption band of Cr(sen)(3+) was 0.077 +/- 0.003.
      Photoaquation of Delta-Cr(sen)(3+) led to loss of optical activity and product
      analysis by capillary electrophoresis showed that both racemic and Delta
      Cr(sen)(3+) photoaquate to a single main product, trans-Cr(sen-NH)(H(2)O)(4+).
      The product stereochemistry is shown to be consistent with predictions based on
      the angular overlap model for Cr(III) photochemistry, recognizing the additional
      constraints imposed by the ligand. The abnormally short room temperature solution
      lifetime of the doublet state is a result of a radiation-less process that
      competes with other processes depleting the doublet state. However, this doublet
      state deactivation process does not lead to photoaquation but competes with BISC
      and photoaquation via the quartet state, resulting in an unprecedented reduction
      in photoaquation quantum yield on direct irradiation into the doublet state.

PMID- 11849090
TI  - Formation constants of copper(I)-olefin complexes in aqueous solution.
AB  - A simple kinetic method has been applied to measure the formation constants of
      aqueous copper(I) with fumaronitrile, dimethyl fumarate, and fumaric and maleic
      acids. At 0.14 M ionic strength, the values of beta(1) are (0.85 +/- 0.02) x
      10(3), (6.1 +/- 0.1) x 10(3), (7.3 +/- 0.1) x 10(3), and (2.2 +/- 0.4) x 10(3) M(
      1), respectively. The values for the last two olefins are compared to previous
      results. Values of beta(1) for hydrogen maleate and beta(2) for fumaronitrile
      also have been determined. A reanalysis of much earlier work has been done, and
      all the results are discussed in terms of the effect of substituents on the
      olefin on the beta(1) values. The structure of bis(fumaronitrile)copper(I)
      nitrate also is reported. The nitrile is N-coordinated to copper(I), which has a
      distorted tetrahedral geometry, while the overall structure consists of
      macrocyclic Cu(6)(fumaronitrile)(6) rings which extend in three dimensions.

PMID- 11849091
TI  - DFT analysis of the activation and breaking of the Mo-N bond in a (mu
      nitrido)dimolybdenum complex: is molybdenum tris(thiolate) an elusive
      intermediate?
AB  - The electronic structure, conformation, synthesis, and thermal decomposition
      pathways of the recently characterized dimolybdenum mu-nitrido complex
      (AdS)(3)Mo(mu-N)Mo(N[(t)Bu]Ph)(3) (1exp, Ad = adamantyl) are investigated by
      means of DFT calculations carried out on the model system (HS)(3)Mo(mu
      N)Mo(NH(2))(3) (1). The observed asymmetry of the Mo(mu-N)Mo core is reproduced
      in the optimal conformation of 1 and assigned to the tendency for the electron
      density of the metal atoms to be preferably accommodated in the pi orbitals of
      Mo(thiolate). The balance in the metal-ligand and ligand-ligand interactions
      conditioning the flow of the electron density along the Mo-(mu-N)-Mo framework,
      and eventually the relative activation of the molybdenum-nitrido bonds, appears
      very sensitive to the nature of the ancillary substituents on both the thiolate
      and the amido sides. On one hand, replacing HS by AdS in 1 increases the
      calculated value of Delta(mu-N-Mo) from 0.053 to 0.094 A, close to the
      experimental value of 0.111 A. The mu-nitrido complex with bulky thiolates 1a is
      also less stable than 1 by 7.3 kcal x mol(-1) with respect to its monometallic
      constituents. On the other hand, substituting the bulky N[(t)Bu]Ph for NH(2) in
      the model complex 1b induces an important charge transfer toward the thiolate
      moiety resulting in structural and energetic consequences of similar magnitude.
      Even though these substitutional effects are not likely to be fully additive in
      the real complex, both should contribute to an increase of the mu-N-Mo(thiolate)
      bond activation in 1exp. The importance of this activation conditions the
      feasibility of the thermal decomposition of 1exp promoted by benzonitrile which
      eventually yields the molybdenum thiolate dimer (RS)(3)Mo [triple bond]
      Mo(SR)(3). The energy profile calculated for this reaction with model complex1 in
      the presence of one or two molecules of acetonitrile shows that the axial
      fixation of the promoter on one or both molecular ends forms intermediates in
      which the mu-N-Mo(thiolate) bond is further activated with respect to the
      original complex. The consequence is an important, but still insufficient,
      decrease of the barrier to Mo-N bond breaking, from 53 to 37 kcal x mol(-1).
      Furthermore, the thermodynamic balance of the reaction leading from the
      acetonitrile adducts of 1 to (HS)(3)Mo [triple bond] Mo(SH)(3) remains
      endothermic by 6.5 kcal x mol(-1) for the monoadduct, and more for the diadduct.
      It therefore appears that bulky substituents on both ends of the dinuclear
      complex are essential to the completion of the reaction, from both the
      thermodynamic and the kinetic viewpoints.

PMID- 11849092
TI  - Nitrous acid as a source of NO and NO(2) in the reaction with a macrocyclic
      superoxorhodium(III) complex.
AB  - The title reaction takes place according to the stoichiometry 2L(2)RhOO(2+) +
      3HNO(2) + H(2)O --> 2L(2)Rh(OH(2))(3+) + 3NO(3)(-) + H(+) (L(2) = meso-Me(6)
      [14]ane-N(4)). The kinetics are second order in HNO(2) and independent of the
      concentration of L(2)RhOO(2+), rate = (k(1) + k(2)[H(+)])[HNO(2)](2), where k(1)
      = 10.9 M(-1) s(-1) and k(2) = 175 M(-2) s(-1) at 25 degrees C and 0.10 M ionic
      strength. The reaction produces two observable intermediates, the nitrato
      (L(2)RhONO(2)(2+)) and hydroperoxo (L(2)RhOOH(2+)) complexes. The product
      analysis and kinetics are indicative of the initial rate-controlling formation of
      NO and NO(2), both of which react rapidly with L(2)RhOO(2+) in subsequent steps.
      The reaction with NO produces mainly L(2)RhONO(2)(2+), which hydrolyzes to
      L(2)Rh(OH(2))(3+) and NO(3)(-). Another minor pathway generates the hydroperoxo
      complex, which was detected by its known reaction with Fe(aq)(2+). The reaction
      of NO(2) with L(2)RhOO(2+) requires an additional equivalent of HNO(2) and
      produces L(2)Rh(OH(2))(3+) and NO(3)(-) via a proposed peroxynitrato complex
      L(2)RhOONO(2)(2+). This work provides strong evidence for the long-debated
      reaction between HNO(2) and H(2)NO(2)(+) to generate N(2)O(3).

PMID- 11849093
TI  - Tetrazolylpentazoles: nitrogen-rich compounds.
AB  - Tetrazolylpentazole was identified as an intermediate in the reaction of
      tetrazolediazonium chloride with lithium azide by low-temperature (15)N NMR
      spectroscopy. The decomposition of (15)N-labeled tetrazolylpentazole to form
      (15)N-labeled tetrazoleazides and dinitrogen was followed by low-temperature
      (15)N NMR spectroscopy. The structures of the species involved in this
      decomposition were optimized at different levels of theory, and the structures of
      the transition states were identified. The activation barriers for the
      decomposition were calculated at different levels of theory.

PMID- 11849096
TI  - SrInGe and EuInGe: new Zintl phases with an unusual anionic network derived from
      the ThSi(2) structure.
AB  - Two new isostructural Zintl phases, EuInGe and SrInGe, are obtained from high
      temperature reactions of the pure elements in welded Ta tubes. Both ternary
      phases crystallize in a new structure type in space group Pnma (No. 62), with a =
      4.921(1) A, b = 3.9865(9) A, and c = 16.004(3) A for EuInGe; and a = 5.021(1) A,
      b = 4.0455(9) A, and c = 16.188(4) A for SrInGe. The crystal structures
      established by single-crystal X-ray diffraction feature zigzag chains of 3-bonded
      Ge atoms and puckered layers of 4-bonded In atoms. The two structural units are
      linked into an anionic network with channels composed of 5-membered and 7
      membered rings. The channels are filled by the respective divalent cations. The
      chemical bonding of the anionic [InGe](2)(-) network, derived from a one-electron
      oxidative distortion of the alpha-ThSi(2) structure, is explained using extended
      Huckel band structure calculations. Magnetic measurements indicate that EuInGe
      exhibits Curie-Weiss paramagnetic behavior above 35 K and antiferromagnetic
      behavior below 35 K. The calculated effective moment, mu(eff) = 8.11 mu(B), of
      EuInGe and the diamagnetic behavior of SrInGe are consistent with the oxidation
      states of Eu(II) and Sr(II), respectively.

PMID- 11849094
TI  - DNA hydrolytic cleavage by the diiron(III) complex Fe(2)(DTPB)(mu-O)(mu
      Ac)Cl(BF(4))(2): comparison with other binuclear transition metal complexes.
AB  - The binuclear structure of Fe(2)(DTPB)(mu-O)(mu-Ac)Cl(BF(4))(2) (DTPB = 1,1,4,7,7
      penta (2'-benzimidazol-2-ylmethyl)-triazaheptane, Ac = acetate) was characterized
      by UV-visible absorption and infrared spectra and NMR and ESR. The binding
      interaction of DNA with the diiron complex was examined spectroscopically.
      Supercoiled and linear DNA hydrolytic cleavage by the diiron complex is supported
      by the evidence from anaerobic reactions, free radical quenching, high
      performance liquid chromatography experiments, and enzymatic manipulation such as
      T4 ligase ligation, 5'-(32)P end-labeling, and footprinting analysis. The
      estimation of rate for the supercoiled DNA double strand cleavage shows one of
      the largest known rate enhancement factors, approximately 10(10) against DNA.
      Moreover, the DNA hydrolysis chemistry needs no coreactant such as hydrogen
      peroxide. The poor sequence-specific DNA cleavage indicated by the restriction
      analysis of the pBR322 DNA linearized by the diiron complex might be due to the
      diiron complex bound to DNA by a coordination of its two ferric ions to the DNA
      phosphate oxygens, as suggested by spectral characterizations. The hydrolysis
      chemistry for a variety of binuclear metal complexes including Fe(2)(DTPB)(mu
      O)(mu-Ac)Cl(BF(4))(2) is compared. It is established that the dominant factors
      for the DNA hydrolysis activities of the binuclear metal complexes are the mu-oxo
      bridge, labile and anionic ligands, and open coordination site(s). Concerning the
      hydrolytic mechanisms, the diiron complex Fe(2)(DTPB)(mu-O)(mu-Ac)Cl(BF(4))(2)
      might share many points in common with the native purple acid phosphatases.

PMID- 11849095
TI  - Nickel(II) complexes with tetra- and pentadentate aminopyridine ligands:
      synthesis, structure, electrochemistry, and reduction to nickel(I) species.
AB  - A series of nickel(II) complexes with polydentate aminopyridine ligands N,N,N'
      tris-[2-(2'-pyridyl)ethyl]ethane-1,2-diamine (L1), N,N,N'-tris-[2-(2'
      pyridyl)ethyl]-N'-methylethane-1,2-diamine (L2), and N,N'-bis-[2-(2'
      pyridyl)ethyl]-N,N'-dimethylethane-1,2-diamine (L3) were synthesized and
      characterized by elemental analysis and spectroscopic methods. Single-crystal X
      ray diffraction studies showed that the Ni(II) ions have five-coordinate square
      pyramidal geometry in [NiL2](ClO(4))(2), similar to that previously found in
      [NiL1](ClO(4))(2) x CH(3)NO(2) (Hoskins, B. F.; Whillans, F. D.J. Chem. Soc.,
      Dalton Trans. 1975, 657), and square-planar geometry in [NiL3](ClO(4))(2). All
      three nickel(II) complexes are reduced by sodium borohydride or sodium amalgam in
      organic solvents to nickel(I) species, which were identified by highly
      anisotropic EPR spectra at 100 K: g(1) = 2.239, g(2) = 2.199, and g(3) = 2.025
      for [NiL1](+); g(axially) = 2.324 and g(radially) = 2.079 for [NiL2](+) and
      [NiL3](+). Cyclic voltammetry of the nickel(II) complexes in acetonitrile
      exhibited reversible reduction waves at -1.01 V for [NiL1](2+), -0.91 V for
      [NiL2](2+), and -0.83 V for [NiL3](2+) versus SCE, potentials which are
      significantly less negative than those of most previously characterized Ni(II)
      complexes with nitrogen-only donor atoms. Complexes [NiL1](2+) and [NiL2](2+)
      showed high catalytic activity in the electroreduction of 1,2-trans
      dibromocyclohexane to cyclohexene.

PMID- 11849097
TI  - Novel DNA sensor for guanine content.
AB  - The bifunctional complex [Ru(TAP)(2)POQ-Nmet](2+), 1, formed with a
      [Ru(TAP)(2)Phen](2+) metallic unit linked to a quinoline moiety, and
      [Ru(TAP)(2)Phen](2+), 2, as reference, have been tested as photoprobes of DNA.
      Interestingly, 1 exhibits an emission enhancement of a factor of 16-17 upon
      binding to calf thymus DNA. Moreover, this emission is modulated by the nucleic
      base content of the polynucleotide. It varies by almost an order of magnitude
      from a polynucleotide containing 100% of G-C to a guanine-free nucleic acid where
      the excited-state lifetime reaches about 2 micros. The origins of these
      interesting properties are analyzed by comparing 1 with reference 2 in the
      presence of different polynucleotides.

PMID- 11849098
TI  - From clusters to ionic complexes: structurally characterized thallium titanium
      double alkoxides.
AB  - A series of sterically varied titanium alkoxides [[Ti(OR)(4)](n)(), n = 4, OR =
      OCH(2)CH(3) (OEt); n = 1, OCH(CH(3))(2) (OPr(i)); n = 2, OCH(2)C(CH(3))(3)
      (ONep); n = 1, OC(6)H(3)(CH(3))(2)-2,6 (DMP)] were reacted with a series of
      thallium alkoxides [[Tl(OR)](x) (x = 4, OR = OEt, ONep; n = infinity, DMP)]. The
      resultant products of the [Tl(mu(3)-OEt)](4)-modified [Ti(OR)(4)](n)() (OR = OEt,
      OPr(i), ONep) were found by X-ray analysis to be Tl(4)Ti(2)(mu-O)(mu(3)
      OEt)(8)(OEt)(2) (1), Tl(4)Ti(2)(mu-O)(mu(3)-OPr(i))(5)(mu(3)-OEt)(3)(OEt)(2) (2),
      and TlTi(2)(mu(3)-OEt)(2)(mu-OEt)(mu-ONep)(2)(ONep)(4) (3), respectively. The
      reaction of [Tl(mu(3)-OEt)](4), 12HOEt, and 4[Ti(mu-ONep)ONep)(3)](2) to generate
      3 in a higher yield resulted in the isolation of TlTi(2)(mu(3)-OEt)(mu(3)
      ONep)(mu-OEt)(mu-ONep)(2)(ONep)(4) (4). Compounds 1 and 2 possess an octahedral
      (Oh) arrangement of two Ti and four Tl metal atoms around a mu-O central oxide
      atom (the Tl-O distance is too long to be considered a bond). For both compounds,
      each Ti atom adopts a distorted Oh geometry with one terminal OEt ligand. The Tl
      atoms are formally 4-coordinated, adopting a distorted pyramidal geometry using
      four mu(3)-OR (OR = OEt or OPr(i)) ligands to complete their coordination sphere.
      The Tl atoms reside approximately 1.4 A below the basal plane of oxygens. In
      contrast to these structures, both 3 and 4 utilize ONep ligands and display
      reduced oligomerization yielding trinuclear complexes without oxo formation. The
      two Ti cations are Oh, and the single Tl cation is in a formal distorted
      pyramidal (PYD) arrangement. If the lone pair of the Tl cations are considered in
      the geometry, each Tl adopts a square base pyramidal geometry. Two terminal ONep
      ligands are bound to each Ti with the remainder of the molecule consisting of
      mu(3)- and mu-ONep ligands. The reaction of [Tl(mu(3)-ONep)](4) with two
      equivalents of [Ti(mu-ONep)(ONep)(3)](2) also led to the isolation of the
      homoleptic trinuclear complex TlTi(2)(mu(3)-ONep)(2)(mu-ONep)(3)(ONep)(4) (5)
      which is analogous in structure to the mixed ligand species of 3 and 4. Each Ti
      is Oh coordinated with six ONep ligands, and the single Tl is PYD bound by ONep
      ligands. A further increase in the steric bulk of the pendant ligands, using
      [Tl(mu-DMP)](infinity) and [Ti(mu-ONep)(ONep)(3)](2), resulted in a further
      decrease in the nuclearity yielding the dinuclear species TlTi(mu-DMP)(mu
      ONep)(DMP)(ONep)(2) (6). For 6, the two metals are bound by a mu-ONep and a mu
      DMP ligand. The Tl metal center was solved in a bent geometry while the Ti
      adopted a distorted trigonal bipyramidal (TBP) geometry using three ONep and two
      DMP ligands to fill its coordination sphere. Further increasing the steric bulk
      of the ancillary ligands using Ti(DMP)(4) and [Tl(mu-DMP)](infinity) led to the
      formation of [Tl(+)][(-)(eta(2-3)-DMP)Ti(DMP)(4)] (7). The Ti metal center is in
      a TBP geometry, and the "naked" Tl cation resides unencumbered by solvent
      molecules but was found to have a strong pi-interaction with four DMP ligands of
      neighboring Ti(DMP)(5)(-) anions. For this novel set of compounds, (205)Tl NMR
      spectroscopy was used to investigate the solution behavior of these compounds.
      Multiple (205)Tl resonances were observed for the solution spectra of the
      crystalline material of 1-6, and a broad singlet was observed for 7. The large
      number of minor resonances noted for these compounds was attributed to
      sensitivity of the Tl cation based on small variations due to ligand
      rearrangement. However, the major resonance noted in the (205)Tl NMR solution
      spectra of 1-7 are in agreement with their respective solid-state structures.

PMID- 11849099
TI  - Heterometal cubane-type MFe(3)S(4) clusters (M = Mo, V) trigonally symmetrized
      with hydrotris(pyrazolyl)borate(1-) and tris(pyrazolyl)methanesulfonate(1-)
      capping ligands.
AB  - A series of heterometal cubane-type clusters containing [VFe(3)S(4)](2+) and
      [MoFe(3)S(4)](3+,2+) cores has been prepared. Ligand substitution of
      [(DMF)(3)VFe(3)S(4)Cl(3)](-) affords [(Tpms)VFe(3)S(4)L(3)](2)(-) (L = Cl(-) (8),
      EtS(-) (9), p-MeC(6)H(4)S(-), p-MeC(6)H(4)O(-)). A new procedure for the
      preparation of molybdenum single cubanes is introduced by the reaction of
      recently reported [(Tp)MoS(S(4))](-) with FeCl(2)/NaSEt to afford
      [(Tp)MoFe(3)S(4)Cl(3)](-) (1, 75% yield). This procedure is more efficient that
      the existing multistep synthesis of single cubanes, which generally affords
      clusters of mirror symmetry. Also prepared were [(Tp)MoFe(3)S(4)L(3)](-) (L =
      EtS(-) (2), p-MeC(6)H(4)S(-)). Reduction of 1 with borohydride gives
      [(Tp)MoFe(3)S(4)Cl(3)](2-) (5, 67%). Owing to the nature of the heterometal
      ligand, all clusters have idealized trigonal symmetry, reflected in their (1)H
      NMR spectra. Trigonal structures are demonstrated by crystallography of
      (Bu(4)N)[1,2], (Bu(4)N)(2)[5] x MeCN, and (Me(4)N)(2)[8,9]. The availability of 1
      and 5 allows the first comparison of structures and (57)Fe isomer shifts of
      [MoFe(3)S(4)](3+,2+) in a constant ligand environment. Small increases in most
      bond distances indicate that an antibonding electron is added in the reduction of
      1. Collective synthetic and electrochemical results from this and other studies
      demonstrate the existence of the series of oxidation states
      [VFe(3)S(4)](3+,2+,1+) and [MoFe(3)S(4)](4+,3+,2+) whose relative stabilities
      within a given series are strongly ligand dependent. Isomer shifts indicate that
      the reduction of 1 largely affects the Fe(3) subcluster and are consistent with
      the formal descriptions [MoFe(3+)(2)Fe(2+)S(4)](3+) (1) and
      [MoFe(3+)Fe(2+)(2)S(4)](2+) (5). Reaction of 1 with excess Li(2)S in acetonitrile
      affords the double cubane [[(Tp)MoFe(3)S(4)Cl(2)](2)(mu(2)(-)S)](2)(-), whose
      sulfide-bridged structure is supported by two sequential reductions separated by
      290 mV, in analogy with previously reported double cubanes of higher charge.
      Trigonally symmetric single cubanes eliminate isomers in the formation of double
      cubanes and other cluster structures, and may be of considerable value in the
      preparation of new types of M-Fe-S clusters. (Tpms =
      tris(pyrazolyl)methanesulfonate(1-); Tp = hydrotris(pyrazolyl)borate(1-).)

PMID- 11849100
TI  - Gas-phase photofragmentation of tris(methyl vinyl ketone) tungsten(0) and the
      relationship to laser-assisted CVD of tungsten oxide thin films.
AB  - The gas-phase laser-induced photofragmentation of tris(methyl vinyl ketone)
      tungsten(0) is studied, and the photoproducts are identified by time-of-flight
      mass spectroscopy. The initially populated excited electronic state of the
      complex is attributed to metal-to-ligand charge transfer by analysis of the
      electronic and preresonance Raman spectra. The major metal-containing
      photofragmentation products are W(+) and WO(+); smaller amounts of WC(+) and
      W(C(2)H(2))(+) are also observed. Intramolecular ligand coupling occurs, and
      dimeric products and their fragments are identified. Reaction pathways that
      explain the observed products are proposed. Thin films on silicon substrates are
      produced by laser-assisted chemical vapor deposition. The films consist of
      polycrystalline tungsten oxide with less than 10% tungsten carbide and are
      characterized by X-ray diffraction, SEM, and Auger electron spectroscopy.
      Relationships between the composition of the gas-phase photofragments and that of
      the solid films are discussed.

PMID- 11849101
TI  - Solid-state structures of zinc(II) benzoate complexes. Catalyst precursors for
      the coupling of carbon dioxide and epoxides.
AB  - Zinc complexes derived from benzoic acids containing electron-withdrawing
      substituents have been synthesized from Zn(II)(bis-trimethylsilyl amide)(2) and
      the corresponding carboxylic acid (2,6-X(2)C(6)H(3)COOH, where X = F, Cl, or OMe)
      in THF and structurally characterized via X-ray crystallography. The 2,6
      difluorobenzoate complex crystallizes from THF or CH(3)CN as a seven membered
      zinc aggregate, where the metal atoms are interconnected by a combination of 10
      mu-benzoates and mu(4)-oxo ligands, that is, [(2,6
      difluorobenzoate)(10)O(2)Zn(7)](solvent)(2), solvent = THF (1) and CH(3)CN (1a).
      On the other hand, the 2,6-dichlorobenzoate zinc derivative crystallizes from THF
      as a dimer, [(2,6-dichlorobenzoate)(4)Zn(2)](THF)(3) (2), where the two zinc
      centers are bridged by three benzoate ligand. One of the zinc centers possesses a
      tetrahedral ligand environment where the fourth ligand is a unidentate benzoate,
      and the other zinc center has an octahedral arrangement of ligands which is
      accomplished by the additional binding of three THF molecules. Upon dissolution
      of complex 1 or 2 in the strongly binding pyridine solvent, disruption of these
      zinc carboxylates occurs with concomitant formation of mononuclear zinc bis
      benzoates with three pyridine ligands in the metal coordination sphere. Complexes
      1 and 2 were found to be effective catalysts for the copolymerization of
      cyclohexene oxide and carbon dioxide to afford polycarbonates devoid of polyether
      linkages, that is, completely alternating copolymers. Although these catalysts or
      catalyst precursors in the presence of CO(2)/propylene oxide afforded mostly
      propylene carbonate, they did serve as efficient catalysts for the
      terpolymerization of carbon dioxide/cyclohexene oxide/propylene oxide. The
      reactivities of these zinc carboxylates were very similar to those previously
      reported analogous complexes which have not been structurally characterized.
      Hence, it is suggested here that all of these zinc carboxylates provide similar
      catalytic sites for CO(2)/epoxide coupling processes.

PMID- 11849102
TI  - Synthesis and characterization of a novel cyclic aluminophosphinate: structure
      and solid-state NMR study.
AB  - We present the structure and a multinuclear solid-state NMR study of a new cyclic
      aluminophosphinate. The crystallographic structure of
      [Al(2)(HC(6)H(5)PO(2))(2)(C(4)H(9)OH)(8)]Cl(4) (compound 1) was obtained at low
      temperature (a = 11.830(7) A, b = 14.216(6) A, c = 17.790(6) A, beta = 91.25(4)
      degrees, monoclinic, P21/c, Z = 2). (13)C IRCP (inversion recovery cross
      polarization) and NQS (non quaternary suppression) NMR experiments allowed the
      complete assignment of the quaternary carbon atom of the phenyl ring and the
      precise determination of the isotropic /(1)J(P-C)/ coupling constant. (31)P CP
      MAS dynamics was carefully studied by varying the contact time. Dipolar
      oscillations even at slow MAS were observed. Up to 11 kHz, these oscillations
      were more pronounced, and the P-H distance was easily extracted. (27)Al NMR
      quadrupolar parameters for 1 were obtained with very good accuracy, and unusual
      satellite transition splitting was observed. Furthermore, the isotropic lines of
      the inner and outer transitions were clearly observable, leading to the
      unambiguous determination of the quadrupolar parameters.

PMID- 11849104
TI  - Synthesis and characterization of novel mononuclear cadmium thiolate complexes in
      a sulfur-rich environment.

PMID- 11849103
TI  - meso Substituent effects on the geometric and electronic structures of high-spin
      and low-spin iron(III) complexes of mono-meso-substituted octaethylporphyrins.
AB  - Introduction of a single meso substituent into ClFe(III)(OEP) or
      K[(NC)(2)Fe(OEP)] results in significant changes in the geometric and/or
      spectroscopic properties of these complexes. The mono-meso-substituted iron(III)
      complexes ClFe(III)(meso-Ph-OEP), ClFe(III)(meso-n-Bu-OEP), ClFe(III)(meso-MeO
      OEP), ClFe(III)(meso-Cl-OEP), ClFe(III)(meso-NC-OEP), ClFe(III)(meso-HC(O)-OEP),
      and ClFe(III)(meso-O(2)N-OEP) have been isolated and characterized by their
      UV/vis and paramagnetically shifted (1)H NMR spectra. The structures of both
      ClFe(III)(meso-Ph-OEP) and ClFe(III)(meso-NC-OEP) have been determined by X-ray
      crystallography. Both molecules have five-coordinate structures typical for high
      spin (S = 5/2) iron(III) complexes. However, the porphyrins themselves no longer
      have the domed shape seen in ClFe(III)(OEP), and the N(4) coordination
      environment possesses a slight rectangular distortion. These high-spin, mono-meso
      substituted iron(III) complexes display (1)H NMR spectra in chloroform-d solution
      which indicate that the conformational changes seen in the solid-state structures
      are altered by normal molecular motion to produce spectra consistent with C(s)
      molecular symmetry. In pyridine solution the high-spin six-coordinate complexes
      [(py)ClFe(III)(meso-R-OEP)] form. In methanol solution in the presence of excess
      potassium cyanide, the low-spin six-coordinate complexes K[(NC)(2)Fe(III)(meso-R
      OEP)] form. The (1)H NMR spectra of these show that electron-donating
      substituents produce an upfield relocation of the meso-proton chemical shifts.
      This relocation is interpreted in terms of increased contribution from the less
      common (d(xz),d(yz))(4)(d(xy))(1) ground electronic state as the meso substituent
      becomes more electron donating.

PMID- 11849105
TI  - Pyramidal inversion isomers in the solid-state structure of the tricyclic
      antimony-tellurium imido complex TeSb(2)Cl(2)(N(t)Bu)(4).

PMID- 11849106
TI  - Novel lanthanide(III) coordination polymers with 1,4-bis(phenyl-sulfinyl)butane
      forming unique lamellar square array: syntheses, crystal structures, and
      properties.

PMID- 11849107
TI  - Reactivity of iron verdohemes with phenylmagnesium bromide. Formation of
      paramagnetic iron-phenyl complexes.

PMID- 11849108
TI  - Synthesis and structural characterization of [Na(2)M(C(5)O(5))(2)(H(2)O)(2)] x
      4H(2)O (M = Ni(II), Cu(II)).

PMID- 11849109
TI  - Ferromagnetic coupling in a ladder-type copper(II) complex with single end-to-end
      azido bridges.

PMID- 11849110
TI  - Lightest member of the basic carboxylate structural pattern: [Al(3)(mu)
      O)(mu(2)CCF(3))(6)(THF)(3)][(Me(3)Si)(3)CAl(O(2)CCF(3))(3)] x C(7)H(8).

PMID- 11849111
TI  - Kinetics of the oxidation of triphenylphosphine by nitric oxide.

PMID- 11849112
TI  - Toward the development of better vaccine adjuvants.

PMID- 11849113
TI  - Immunotherapy of hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is the third leading cause of cancer death, with
      over a million new cases annually. It is generally advanced upon detection due to
      underlying liver disease, which further complicates treatment. Most of the
      therapeutic strategies in current use (surgery, transplantation, irradiation or
      chemotherapy) are either palliative or only of benefit to a small percentage of
      patients. This article reviews the biology of HCC, including many of the
      molecular changes and mechanisms leading to HCC development. This article
      discusses the recent innovative strategies to interfere with the progression of
      HCC, including novel gene therapy strategies. The most recent data supporting the
      use of immunotherapy for hepatocellular cancer is reviewed in detail.

PMID- 11849115
TI  - Gene therapy for Parkinson's disease.
AB  - Significant progress has been made in the field of gene therapy for Parkinson's
      disease (PD). Successful vehicles for gene transfer into the central nervous
      system have been developed and clinical efficacy and safety have both been shown
      in various animal models of PD. Further optimisation of dosing, timing and
      location of gene therapy delivery as well as the ability to regulate and prolong
      gene expression will be important for the commencement of human trials. Current
      gene therapy models for PD have focused on two treatment strategies. One is the
      replacement of biosynthetic enzymes for dopamine synthesis and the second
      strategy is the addition of neurotrophic factors for protection and restoration
      of dopaminergic neurones. Concepts of neuroprotection and restoration of the
      nigrostriatal pathway will become important themes for future genetic treatment
      strategies for PD and may include, in addition to neurotrophic factors, genes to
      prevent apoptosis or detoxify free radical species. This review will highlight
      the recent literature on gene therapy for PD and summarise general approaches to
      gene therapy.

PMID- 11849114
TI  - Cytokine inhibitors in the treatment of rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is an immune-mediated disease characterised by
      articular inflammation and subsequent tissue damage leading to severe disability
      and increased mortality. A variety of cytokines are produced locally in the
      rheumatoid joints. Numerous studies have demonstrated that IL-1 and TNF-alpha,
      two prototypic pro-inflammatory cytokines, play an important role in the
      mechanisms involved in synovial inflammation and in progressive joint
      destruction. Indeed, the administration of TNF-alpha and IL-1 inhibitors in
      patients with RA led to a dramatic improvement of clinical and biological signs
      of inflammation and a reduction of radiological signs of bone erosion and
      cartilage destruction. However, despite these encouraging results, a significant
      percentage of patients do not respond to these agents, suggesting that other
      mediators are also involved in the pathophysiology of arthritis. This review
      describes the results of clinical trials with TNF-alpha inhibitors and a specific
      IL-1 inhibitor (IL-1 receptor antagonist [IL-1Ra]). In addition, other
      therapeutic strategies are also discussed.

PMID- 11849116
TI  - Gene therapy for malignant liver disease.
AB  - For most patients with advanced or multifocal hepatocellular carcinoma (HCC) or
      with metastatic malignant liver disease treatment options are limited, resulting
      in a poor prognosis. Novel therapeutic strategies such as gene therapy are
      therefore urgently required. Gene therapeutic approaches use gene delivery
      systems (vectors) to introduce DNA constructs as therapeutic agents into living
      cells. Antitumour strategies include the reintroduction of tumour suppressor
      genes into tumour cells, the expression of foreign enzymes to render tumours
      susceptible to treatment with chemotherapeutic agents and the enhancement of
      tumour immunogenicity by expressing immunomodulatory genes or by genetic
      vaccination with tumour antigens. Furthermore, gene therapy may be also used for
      anti-angiogenesis to reduce tumour growth and metastatic potential. Other novel
      approaches aim at the development of genetically altered replication competent
      viruses, which selectively replicate in tumour cells inducing cell lysis.
      Although most clinical trials of antitumour gene therapy so far have failed to
      induce strong therapeutic effects, further improvement of antitumour gene therapy
      may finally result in potent clinical treatment options for patients with
      malignant liver tumours.

PMID- 11849117
TI  - Head and neck cancer: gene therapy approaches. Part 1: adenoviral vectors.
AB  - Treatment options for recurrent or refractory head and neck cancer are limited.
      The goal of gene therapy is to introduce new genetic material into cancer cells
      without affecting toxicity to surrounding malignant cells. The most common
      vehicles for delivery of genes are adenoviruses. Adenoviruses gain access to
      malignant and normal cell cytoplasm via viral ligand binding to a unique cell
      surface receptor (the coxsackie adenovirus receptor [CAR]). However, this
      receptor is not cancer specific. Genetic modification of adenoviral DNA can
      create cancer specific targeting. Adenoviruses can be modified to express cancer
      specific ligands thereby focusing binding to malignant tissue. Furthermore,
      adenoviral delivered genes can be put under cancer specific promoter control to
      further limit gene expression in malignant tissue. Increased antitumour activity
      from such modifications has been demonstrated preclinically and several clinical
      trials have been completed demonstrating safety and clinical activity of non
      replicating and conditional replicating adenoviral vector thereby opening the
      door for gene delivery and cancer specific targeting.

PMID- 11849118
TI  - Active immunisation against human tick-borne diseases.
AB  - With the development and licensure of a recombinant vaccine for the tick-borne
      infection Lyme disease, more attention has been paid to other vaccines that have
      been used or are being developed for the prevention of other tick-borne
      infections. This review highlights vaccine information for Lyme borreliosis, tick
      borne encephalitis (TBE), Rocky Mountain spotted fever, tularaemia, Query (Q)
      fever, Kyasanur Forest disease (KFD) and tick paralysis. Additionally, discussion
      on the use of immunisation against the tick itself is included which not only can
      decrease veterinary tick burdens but may also decrease the transmission of
      arthropod-transmitted diseases.

PMID- 11849119
TI  - Use of marine toxins in combination with cytotoxic drugs for induction of
      apoptosis in acute myelogenous leukaemia cells.
AB  - Intensive chemotherapy for acute myelogenous leukaemia (AML) results in an
      overall long-term disease-free survival of < 50%. This percentage reflects an
      improved survival for certain subsets of patients with low-risk cytogenetic
      abnormalities after treatment with high-dose cytarabine, whereas lower long-term
      survival is seen for other patients and especially for the large group of elderly
      patients. New treatment strategies are therefore considered in AML and one
      approach is to target the regulation of apoptosis in AML cells with new
      pharmacological agents. Regulation of apoptosis seems to be clinically important
      in AML as intracellular levels of apoptosis-regulating mediators can be used as
      predictors of prognosis in AML. It is also well documented that cytotoxic drugs
      exert important antileukaemic effects through induction of apoptosis. Marine
      toxins represent new pharmacological agents with proapoptotic effects and should
      be considered for combination therapy with cytotoxic drugs. These agents are
      already useful laboratory tools for in vitro studies of AML cells but it is still
      too early to conclude whether they will become useful in clinical therapy. One of
      the major problems to be investigated is the toxicity of combination therapy,
      although this may be solved by the coupling of toxins to antibodies or growth
      factors with a preferential binding to AML cells. Other problems that have to be
      addressed are the possible effect of the toxins' tumour promoting effects on
      chemosensitivity in relapsed AML and the possibility of cross-resistance between
      cytotoxic drugs and toxins.

PMID- 11849120
TI  - Becaplermin: recombinant platelet derived growth factor, a new treatment for
      healing diabetic foot ulcers.
AB  - Chronic or non-healing lower extremity ulcerations in diabetics are a significant
      cause of morbidity and mortality, and account for a large proportion of the
      financial burden related to the care of diabetics. Lower extremity ulcerations
      develop primarily as a consequence of neuropathy and the goal in addressing any
      wound is to re-establish tissue integrity as soon as possible. The healing of
      wounds is a complex procedure involving multiple growth factors, some of which
      have multiple effects on different cell types, in particular, platelet derived
      growth factor (PDGF) is a prominent agent, active in all stages of the healing
      process. Becaplermin (0.01% Regranex gel) is a homodimeric protein produced by
      recombinant DNA technology through the insertion of the gene for the B chain PDGF
      into the yeast Saccharomyces cerevisiae. The biological activity of becaplermin
      is similar to that of indigenous PDGF-BB, specifically, the promotion of
      chemotactic recruitment and the proliferation of cells involved in wound repair.
      Becaplermin has undergone extensive animal and human studies, demonstrating that
      it is highly effective as an adjunctive measure for the healing of ulcerations in
      the feet of diabetics when used in conjunction with standard wound healing
      practices. Specifically these practices include the provision of a moist
      environment free of debris and necrotic tissue, control of infection and optimal
      weight displacement from the affected area. Becaplermin is safe and easy to use,
      being applied once-daily and at present, becaplermin is the only growth factor
      licensed for use in wound healing.

PMID- 11849122
TI  - Review article: natural history and epidemiology of Helicobacter pylori
      infection.
AB  - Helicobacter pylori is a common bacterium infecting about half the world's
      population. It is causally linked with a diverse spectrum of gastrointestinal
      clinical disorders including peptic ulcer disease, gastric cancer, and gastric
      MALT lymphoma. The principal reservoir is the human stomach, and transmission
      probably occurs by person-to-person passage. Prevalence rates are generally much
      higher in developing countries compared to developed countries, although there
      are subgroups within many regions with higher H. pylori prevalence than in the
      general population. The prevalence of H. pylori varies by geographical location,
      ethnic background, socioeconomic conditions, and age. Recent studies suggest
      decreasing prevalence in developed countries or those with rapidly improving
      socioeconomic conditions. Comparative studies of the two fully sequenced H.
      pylori genomes are providing understanding of its large genetic diversity and
      bacterial virulence factors. The discovery of the type IV secretion system in H.
      pylori and its role in translocation of the CagA protein from the bacterial cell
      into the host epithelial cell provides insight into how host-bacterial
      interaction may lead to host disease. Cytokine promoter polymorphisms are
      determinants important in host gastric acid secretion status. Understanding the
      changing trends in H. pylori epidemiology, details of its transmission pathways,
      and the bacterial and host determinants leading to gastroduodenal disease remain
      the challenges in this area. Global epidemiological studies, advances in
      technology, and medical interventions have converged to help clarify the
      mechanisms of interaction between this ubiquitous micro-organism and its host
      that result in its diverse clinical manifestations.

PMID- 11849123
TI  - Review article: diagnosis of Helicobacter pylori infection.
AB  - Helicobacter pylori (H. pylori) infection can be diagnosed by invasive techniques
      requiring endoscopy and biopsy (histological examination, culture, polymerase
      chain reaction) and by noninvasive techniques (serology, urea breath test, urine
      or blood, detection of H. pylori antigen in stool specimen). At present, no
      single test can be absolutely relied upon to detect colonization by H. pylori,
      and a combination of two tests is recommended if feasible. The tests used should
      depend on the clinical circumstances, the likelihood ratio of positive and
      negative tests, the cost-effectiveness of the testing strategy, and the
      availability of the tests. Some clinical circumstances warrant invasive studies,
      principally patients with alarm symptoms (bleeding, weight loss, etc.) as well as
      older patients with new-onset dyspepsia. Endoscopy may also be advisable in
      patients who have failed eradication therapy and need culture and antimicrobial
      sensitivity testing to determine an appropriate regimen. Recent studies have also
      demonstrated that a strategy to 'test and treat' for H. pylori in uninvestigated,
      young (< 50 years), dyspeptic patients in primary care is safe and reduces the
      need for endoscopy. Indeed, a number of clinical guidelines recommend noninvasive
      testing followed by treatment of H. pylori for dyspeptic patients in primary care
      based on clinical and economic analyses.

PMID- 11849124
TI  - Review article: treatment of Helicobacter pylori infection and factors
      influencing eradication.
AB  - Currently available Helicobacter pylori eradication therapies are considered very
      effective and safe. The most recent eradication guidelines proposed in the
      Maastricht 2-2000 Consensus Report recommend the use of proton pump inhibitors
      (standard b.d.) along with clarithromycin (500 mg b.d.) and amoxycillin (1000 mg
      b.d.) or metronidazole (500 mg b.d.) for a minimum of 7 days. The combination of
      amoxycillin and clarithromycin is preferred because it may favour best results
      with a second-line proton pump inhibitor quadruple therapy. The recommended
      second-line therapy includes a combination of a proton pump inhibitor (standard
      b.d.) with bismuth salt (subsalicylate/subcitrate 120 mg q.d.s.), metronidazole
      (500 mg t.d.s.), and tetracycline (500 mg q.d.s.) for a minimum of 7 days.
      Extended proton pump inhibitor-based triple therapy can be used if bismuth is not
      available. Specialists should manage subsequent failures. Based on direct and
      indirect evidence from well-designed studies and clinical experience, eradication
      is recommended in gastric and duodenal ulcers, MALToma, atrophic gastritis,
      postgastric cancer resection, and in first-degree relatives of gastric cancer
      patients. The most common reason for treatment failure is poor compliance with
      eradication guidelines. Antibiotic resistance may be a significant factor in
      certain geographical areas. Proton pump inhibitors are an integral part of the
      eradication regimens as proved by meta-analyses of clinical trials. Novel agents
      used in secondary failure are few and depend on the use of new antibiotics. The
      role of H. pylori-specific antibiotics, probiotics, and vaccines is not
      established as yet. Widespread acceptance of the eradication guidelines should be
      regarded as the single most important factor in eradication success.

PMID- 11849126
TI  - Review article: the effect of Helicobacter pylori infection on nonsteroidal anti
      inflammatory drug-induced upper gastrointestinal tract injury.
AB  - Helicobacter pylori and nonsteroidal anti-inflammatory drugs (NSAIDs) are the two
      major causes of peptic ulcers. This article reviews the interaction of H. pylori
      and NSAIDs on the development of gastric mucosal histological changes,
      endoscopically confirmed ulcers, and ulcer complications, and assesses whether
      underlying H. pylori infection potentiates (or mitigates) the development of
      NSAID-induced ulcer disease. The weight of evidence does not suggest that H.
      pylori infection potentiates the risk of ulcer formation or ulcer complications
      in NSAID users. If such an effect occurs, it is likely to be relatively small.
      Some data even suggest that H. pylori may be protective against NSAID-induced
      gastric ulcers. Limited data raise the possibility that H. pylori infection,
      however, may potentiate the effect of low-dose aspirin with respect to ulcer
      bleeding. Both NSAIDs and H. pylori are independent risk factors for ulcer
      disease. Therefore, in an individual patient with an ulcer, one cannot be certain
      which factor is responsible for the ulcer, and both risks should be removed if
      possible.

PMID- 11849125
TI  - Review article: rabeprazole-based therapy in Helicobacter pylori eradication.
AB  - Rabeprazole's favourable pharmacodynamic profile is a result of its rapid onset
      and its 24-h control of gastric parietal secretion. These qualities, and its
      antimicrobial properties, make it particularly effective in the treatment of
      Helicobacter pylori (H. pylori), which is a short course of treatment compared to
      other conditions treated with proton pump inhibitors. Recently completed trials
      in combination with amoxicillin, clarithromycin and metronidazole for 7 days
      achieved high eradication of H. pylori. An additional study assessing the
      efficacy of combined rabeprazole and antibiotic treatments of 3, 7, and 10 days'
      duration vs. FDA-approved 10-day omeprazole triple therapy is under way to
      address the possibility of shorter duration therapies in the USA.

PMID- 11849127
TI  - Review article: Helicobacter pylori and gastric adenocarcinoma.
AB  - Gastric adenocarcinoma is still the second most common cause of death from
      cancer, even though it is on the decline in developed countries. Although H.
      pylori gastritis appears to be a necessary antecedent to the development of
      gastric adenocarcinoma, it is not a sufficient factor in and of itself. Other
      required factors for the progression of this disease are poorly understood.
      Patients with antral predominant gastritis seem protected from the disease, while
      patients with pangastritis are predisposed to both diffuse- and intestinal-type
      adenocarcinoma. Development of a vaccine against H. pylori might yield promising
      results in decreasing the incidence of gastric adenocarcinoma.

PMID- 11849128
TI  - Review article: gastro-oesophageal reflux disease and Helicobacter pylori
      infection.
AB  - Gastro-oesophageal reflux disease (GERD) and Helicobacter pylori infection are
      common conditions that frequently coexist. Controversy continues regarding the
      role of H. pylori infection in GERD. The results of some studies suggest that
      eradication of H. pylori may increase the risk for developing GERD, and some
      experts have suggested that chronic H. pylori infection may be of benefit. This
      article reviews the data on H. pylori infection and GERD and its treatment.

PMID- 11849129
TI  - Review article: Helicobacter pylori and uninvestigated dyspepsia.
AB  - Although dyspepsia is a very common disorder, the incidence of Helicobacter
      pylori infection in Western medical clinics is very low (20-35%). In cases where
      H. pylori is detected, elimination of it may be cost-effective in the long term,
      but even eradication is not a guarantee for long-term relief. Further studies to
      determine the connection between H. pylori and dyspepsia need to be completed
      before H. pylori eradication becomes the treatment of choice for that minority of
      patients. The majority of dyspeptic patients are not as simple to diagnose, and
      may need several empirical trials of therapy, or more specific diagnostic
      assessment.

PMID- 11849130
TI  - Review article: Helicobacter pylori and nonulcer dyspepsia.
AB  - Although up to 50% of patients diagnosed with nonulcer dyspepsia (NUD) have
      Helicobacter pylori infection and underlying chronic gastritis, it remains
      controversial whether any causal relationship exists. The results of worldwide
      epidemiological studies have been unconvincing. No clear-cut link has been
      documented between H. pylori and any specific symptom profile or
      pathophysiological mechanism in NUD. In the randomized controlled trials,
      methodological weaknesses may explain in part the conflicting results, but even
      in the well-conducted trials controversy persists. Although meta-analyses have
      attempted to resolve the issue, inherent methodological difficulties with meta
      analysis remain a problem. Moreover, even the methodologically sound meta
      analyses have reported conflicting results. In addition, predictors of treatment
      response remain obscure, and there continue to be theoretical concerns about the
      treatment of H. pylori infection in all patients with NUD. Hence, the management
      of these patients is challenging, but eradication of H. pylori infection may be
      beneficial in a small subgroup of cases with NUD that cannot be identified before
      treatment.

PMID- 11849131
TI  - Review article: Helicobacter pylori infection in peptic ulcer haemorrhage.
AB  - In this overview, medical advice for routine clinical practice regarding peptic
      ulcer haemorrhage (PUH) is given, based on the extensive literature about
      Helicobacter pylori and the controversial results about the interaction of H.
      pylori infection and nonsteriodal anti-inflammatory drug (NSAID) use. PUH remains
      an important emergency situation with an incidence between 32 and 51/100 000
      persons per year. There is a high association between H. pylori infection and
      peptic ulcer disease. The association between H. pylori infection and PUH is less
      clear, but a strong argument for the aetiological role is the fact that
      eradication of H. pylori decreases recurrence of bleeding. NSAID use is another
      important risk factor for PUH. H. pylori infection and NSAID use seem to act
      independently, although some studies show a synergistic interaction while other
      studies report that H. pylori is protective against the development of PUH in
      NSAID users. All patients with PUH should be tested for H. pylori infection,
      regardless of the use of NSAIDs. Because invasive tests are less sensitive in PUH
      patients, negative tests in patients with no other risk factors should be
      confirmed by serology or urea breath test (UBT). Eradication therapy with a
      proton pump inhibitor or ranitidine bismuth citrate-based triple therapy should
      be given to all H. pylori-positive patients. Only for nonaspirin-NSAID users does
      the effect of eradication therapy on the healing of gastric ulcers remain
      controversial, but currently we also advise eradication of H. pylori in this
      subgroup. After eradication therapy, acid-suppressant therapy is advised to heal
      the ulcer. The success of eradication should always be confirmed because of the
      risk of recurrence of peptic ulcer disease and bleeding in H. pylori-infected
      patients.

PMID- 11849132
TI  - Isolation of porcine expressed sequence tags for the construction of a first
      genomic transcript map of the skeletal muscle in pig.
AB  - To identify genes with effects on meat quality and production traits we developed
      an adult porcine skeletal muscle cDNA library. After pre-screening this library
      with seven genes highly expressed in skeletal muscle, 385 non-hybridizing clones
      were sequenced from both ends to yield 510 expressed sequence tags (ESTs).
      Together with those ESTs previously generated from this library, we have produced
      701 porcine skeletal muscle ESTs. These ESTs were grouped into 306 different cDNA
      species and compared with the human skeletal muscle transcriptional profiles
      obtained from different databases. Furthermore we mapped 107 of these cDNAs using
      a somatic cell hybrid panel with genes mapping over all the autosomes (except on
      chromosome 11) and on chromosome X. The mapping of these cDNAs contributed to the
      construction of a first genomic transcript map of the skeletal muscle tissue in
      pig.

PMID- 11849134
TI  - Approaches to interval mapping of QTL in a multigeneration pedigree: the example
      of porcine chromosome 4.
AB  - Quantitative trait loci (QTLs) have been mapped in many studies of F2 populations
      derived from crosses between diverse lines. One approach to confirming these
      effects and improving the mapping resolution is genetic chromosome dissection
      through a backcrossing programme. Analysis by interval mapping of the data
      generated is likely to provide additional power and resolution compared with
      treating data marker by marker. However, interval mapping approaches for such a
      programme are not well developed, especially where the founder lines were
      outbred. We explore alternative approaches to analysis using, as an example, data
      from chromosome 4 in an intercross between wild boar and Large White pigs where
      QTLs have been previously identified. A least squares interval mapping procedure
      was used to study growth rate and carcass traits in a subsequent second backcross
      generation (BC2). This procedure requires the probability of inheriting a wild
      boar allele for each BC2 animal for locations throughout the chromosome. Two
      methods for obtaining these probabilities were compared: stochastic or
      deterministic. The two methods gave similar probabilities for inheriting wild
      boar alleles and, hence, gave very similar results from the QTL analysis. The
      deterministic approach has the advantage of being much faster to run but requires
      specialized software. A QTL for fatness and for growth were confirmed and, in
      addition, a QTL for piglet growth from weaning at 5 weeks up to 7 weeks of age
      and another for carcass length were detected.

PMID- 11849133
TI  - Phylogenetic relationships of Asian and European pig breeds determined by
      mitochondrial DNA D-loop sequence polymorphism.
AB  - Phylogenetic relationships among Asian and European pig breeds were assessed
      using 1036 bp of mitochondrial DNA (mtDNA) D-loop sequences. An unweighted pair
      group method with arithmetic mean (UPGMA) tree was constructed on the basis of
      maximum likelihood distances using sequences determined for three Cheju (Korea),
      11 Chinese, one Westran (Australian feral origin) and two European pigs
      (Berkshire and Welsh), and also published sequences for four Japanese (including
      two Wild Boars), one Yucatan miniature, five European (including Large White,
      Landrace, Duroc, Swedish and Wild Boar) and two Meishan pigs. The Colombian
      collared peccary (Tayassu tajacu) sequence was also determined and used as an
      outgroup. The maximum parsimony with heuristic search method was used to
      determine bootstrap support values. Asian-type pigs clustered together (bootstrap
      support 33%), but were separate from European-type pigs that also clustered
      together (93%). The Westran pig, derived from the feral descendants of pigs
      inhabiting Kangaroo Island of South Australia, clustered with Asian pigs,
      demonstrating Asian origin of their mitochondria. Berkshire and Large White
      clustered with Asian pigs, indicating that Asian pigs were involved in the
      development of these breeds. Our findings clearly demonstrate that pigs
      indigenous to China, Korea and Japan are only recently diverged from each other
      and distinctly different from European-type pigs. European pig breeds consist of
      pigs with mitochondria of Asian and non-Asian type, some of which were formed
      from closely related maternal ancestors, if not from a single ancestor.

PMID- 11849135
TI  - Parental assignment in fish using microsatellite genetic markers with finite
      numbers of parents and offspring.
AB  - Deterministic predictions for the proportion of offspring assigned to different
      numbers of parent-pairs are developed in order to investigate the power of
      microsatellite loci for parental assignment in fish species. Comparisons with
      stochastic simulation results show that predictions based on exclusion
      probabilities are accurate, provided that the number of parents involved in the
      crosses is large. Accounting for sampling of parents gave very accurate
      predictions for a small number of parents and a single biallelic locus. For large
      numbers of loci or large numbers of alleles per locus stochastic simulations are,
      however, the only available method to predict the power of assignment of a
      particular set of loci when the number of parents is small. Nine 5-allele loci or
      six 10-allele loci with equifrequent alleles, are sufficient for assigning, with
      certainty, parents to 99% of the fish resulting from either 100 or 400 crosses.
      Results simulating a set of highly polymorphic microsatellites developed for
      Atlantic salmon show that the four most informative loci are sufficient to assign
      at least 99% of the offspring to the correct pair with 100 crosses involving 100
      males and 100 females. An additional locus is required for correctly assigning
      99% of the offspring when the 100 crosses are produced with 10 males and 10
      females.

PMID- 11849137
TI  - Indications of associations of the porcine FOS proto-oncogene with skeletal
      muscle fibre traits.
AB  - Skeletal muscle fibre characteristics are key determinants of meat quality. High
      fibre diameters and shifting towards higher white fibre proportions lead to
      increasing R-values (degree of desamination of adenosine) and lactate-production,
      resulting in high incidences of pale, soft, exudative (PSE) meat and stress
      susceptibility in European and American pig breeds. Development of muscle fibres
      including their enzymes, is regulated by the MyoD-gene family together with
      transcription factors like FOS. We report on the associations between the
      chromosomal region of FOS with skeletal muscle fibre and metabolism traits. The
      BB genotype representing the European Pietrain breed had 10.9% more white fibres
      with fibre diameters decreased by 6.1%, with 3.9% higher R-values and 8.5% higher
      lactate levels than the AA genotype of the Chinese Meishan. Lactate levels and R
      values per microm of fibre diameter were increased to 18.4 and 11.6% in the BB
      genotype. The contrast between the two quantitative trait loci (QTL) alleles
      associated with a polymorphism in the FOS gene explained up to 5.13% of the total
      variance. A new TaiI-restriction fragment length polymorphism (RFLP) connected to
      a Asn258/Ser mutation, located in a transcription activator region, was used to
      map FOS between markers S0115 and Sw581 on SSC7. The QTLs for skeletal muscle
      fibre and metabolism traits have been mapped to the marker interval around FOS.
      The present data suggest that variability in FOS gene may underlie phenotypic
      variation in skeletal muscle fibre and metabolism traits in the pig.

PMID- 11849136
TI  - Localization of the muscular dystrophy AM locus using a chicken linkage map
      constructed with the Kobe University resource family.
AB  - A chicken linkage map, constructed with the Kobe University (KU) resource family,
      was used to locate the genetic locus for muscular dystrophy of abnormal muscle
      type (AM). The KU resource family is a backcross pedigree with 55 offspring
      produced from the mating of a White Leghorn F-line (WL-F) male and a hybrid
      female produced from a cross between the WL-F male and a female of the Fayoumi
      OPN line who was homozygous for the AM gene. In total, 872 loci were genotyped on
      the pedigree; 749 (86%) were informative and mapped to 38 linkage groups. These
      informative loci included 649 AFLPs, 93 MS, three functional genes, the AM locus,
      sex phenotype, and two red blood cell loci. The remaining 123 markers were
      unlinked. Nineteen of the 38 KU linkage groups were assigned to macrochromosomes
      1-8 and 11 microchromosomes including chromosome W, while 19 linkage groups were
      unassigned. The total map was 3569 cM in length, with an average marker interval
      of 4.8 cM. The AM locus was mapped 130 cM from the distal end of chromosome 2q.

PMID- 11849138
TI  - Homogeneity of recombination rate within a conserved region on BTA3 that contains
      QTL.
AB  - The D3S20-D3S34-D3S3 region on BTA3 contains quantitative trait loci (QTL)
      controlling milk production traits. This region also displays extensive
      conservation of synteny among several species including cattle, humans, mice and
      sheep. In this study, we evaluated the adjacent intervals D3S20-D3S34 and D3S34
      D3S3 for differences in recombination rate (theta) among bulls in order to assess
      the suitability of population-based estimates of theta for marker assisted
      selection and to explore the relationship between variation in theta and
      chromosome breakpoints associated with mammalian evolution. Using sperm typing,
      thetaD3S20-D3S34 and theta D3S34-D3S3 were estimated for six triply heterozygous
      bulls. Recombination frequency ranged from 6.2 to 12.5% and from 9.7 to 19.2% for
      the D3S20-D3S34 and D3S34-D3S3 intervals, respectively. However, significant
      variation in theta was not detected between bulls for either interval (D3S20
      D3S34 chi(2)5 d.f.=2.59, P < 0.90; D3S34-D3S3 chi(2)5 d.f.=3.72, P < 0.75). The
      observed differences in theta were most readily attributed to differences in
      allele-specific amplification efficiencies among bulls. Our results suggest that
      the positions of QTL in this region can be reliably determined from population
      data and therefore accurate marker-assisted selection can be performed for
      desirable alleles without concern for variation in theta. Furthermore, when
      considered with results of earlier studies, these findings support a correlation
      between the existence of evolutionary breakpoints or chromosome rearrangements
      and variation in theta.

PMID- 11849140
TI  - Development of microsatellite markers and comparative mapping for bovine
      chromosome 19.
AB  - Previous research has mapped an ovulation rate quantitative trait locus (QTL) to
      bovine chromosome 19. In an effort to enhance comparative mapping information and
      develop additional markers for refined QTL mapping, microsatellite markers were
      developed in a targeted approach. A bovine bacterial artificial chromosome (BAC)
      library was screened for loci with either known or predicted locations on bovine
      chromosome 19. An average of 6.4 positive BAC were identified per screened locus.
      A total of 10 microsatellite markers were developed for five targeted loci with
      heterozygosity of 7-83% in a sample of reference family parents. The newly
      developed markers were typed on reference families along with four previously
      mapped marker loci and used to create a linkage map. Comparison of locus order
      between human and cattle provides support for previously observed rearrangement.
      One of the mapped loci myotubularin related protein 4 (MTMR4) potentially extends
      the proximal boundary of a conserved linkage group.

PMID- 11849139
TI  - Lack of association of GH1 and POU1F1 gene variants with meat production traits
      in Piemontese cattle.
AB  - Growth hormone (GH) and the Pit-1 transcription factor have been shown to be
      involved in the physiological mechanisms related to growth. The present study was
      carried out to investigate the possible association of the polymorphism at GH1
      and POU1F1 loci with meat production traits in Piemontese cattle. Fourteen traits
      were considered, expressing growth (weight at 5, 7 and 11 months, daily gain),
      size [withers height (WH), trunk length (TL), chest girth (CG) at 12 months] and
      meat conformation [withers width (WW), shoulder muscularity (SM), loin width
      (LW), loin thickness (LT), thigh muscularity (TM), thigh profile (TP), bone
      thinness (BT)]. Data were analysed with a mixed model procedure to estimate the
      allele substitution and the dominance effects. The results did not provide
      evidence of association of GH1 and POU1F1 polymorphisms with the evaluated
      traits.

PMID- 11849141
TI  - A case of intersexuality in pigs associated with a de novo paracentric inversion
      9 (p1.2; p2.2).
AB  - In several mammalian species, genetic defects can be responsible for the
      interruption of and/or the deviation from the sequential steps of normal gonadal
      differentiation, leading to a sex-reversal syndrome. In pigs, female-to-male sex
      reversal conditions are particularly frequent, but their aetiologies remain
      unclear. Chromosomal abnormalities that co-occur with sex-reversal disorders can
      be useful in the identification of loci containing responsible or susceptibility
      genes. This report describes a female-to-male SRY-negative intersex pig with a de
      novo paracentric inversion of the short arm of one chromosome 9 (p1.2; p2.2). We
      have fine mapped the proximal chromosomal breakpoint of this rearrangement
      because it corresponded to a region potentially involved in the pig
      intersexuality. Fluorescent in situ hybridization (FISH) experiments carried out
      with Bacterial Artificial Chromosome (BAC) clones located within the critical
      region defined by genetic linkage analysis and ordered on the porcine RH map
      allowed us to locate the proximal breakpoint between markers SW2571 and SW539.
      Further investigations are currently in progress to find new markers inside this
      interval, in order to determine the BAC in which the break occurred.

PMID- 11849142
TI  - Porcine BAC derived microsatellites linked to ADRBK1, CNTF and GAL on SSC2.

PMID- 11849143
TI  - A missense mutation in the porcine mitochondrial 2,4-dienoyl CoA reductase 1
      (DECR1) gene and linkage mapping of this locus to chromosome 4.

PMID- 11849144
TI  - A radiation hybrid map of bovine chromosome 27.

PMID- 11849145
TI  - Eighteen polymorphic microsatellite markers for rainbow trout (Oncorhynchus
      mykiss).

PMID- 11849147
TI  - Eleven single nucleotide polymorphisms (SNPs) at a hypervariable locus on pig
      chromosome 6.

PMID- 11849146
TI  - Mapping the transferrin gene in tilapia.

PMID- 11849148
TI  - Linkage mapping of a HaeIII PCR-RFLP within the porcine EXT1 gene.

PMID- 11849149
TI  - Rejection of MITF and MGF as the genes responsible for appaloosa coat colour
      patterns in horses.

PMID- 11849150
TI  - How should patients be followed up after radical nephrectomy for renal cell
      cancer?

PMID- 11849151
TI  - Gene amplification and overexpression of HER2 in renal cell carcinoma.
AB  - OBJECTIVE: To determine the frequency of HER2 genetic abnormalities in renal cell
      carcinoma (RCC) and hence assess the potential suitability of Herceptin
      immunotherapy. PATIENTS AND METHODS: Tumours from 27 patients with RCC were
      assessed; all patients had undergone nephrectomy. Benign renal tissue from the
      nephrectomy specimens was studied in seven patients. Gene amplification was
      assessed using fluorescent in-situ hybridization, and protein over-expression
      using immunohistochemistry. RESULTS: Twenty-four patients had clear cell renal
      carcinoma, two had papillary renal carcinoma and one a sarcomatoid variant
      carcinoma. There was no HER2 amplification in the tumours or the benign renal
      tissue. Polysomy 17 was detected in 11 of 27 tumours (41%) and increased HER2
      copy number in seven (26%). Both polysomy 17 and increased HER2 copy number were
      absent in the benign renal tissue. Three tumours (11%) and six of the seven
      benign renal tissue samples over-expressed the HER2 protein. CONCLUSIONS: HER2
      amplification is absent and protein over-expression uncommon in RCC. This casts
      doubt on the suitability of Herceptin in the treatment of RCC.

PMID- 11849152
TI  - Health-related quality of life after radical cystectomy for bladder cancer: a
      comparison of ileal conduit and orthotopic bladder replacement.
AB  - OBJECTIVE: To compare the health-related quality of life (HRQoL) after radical
      cystectomy in patients with an ileal conduit or an orthotopic neobladder.
      PATIENTS AND METHODS: The study included 85 men who underwent radical cystectomy
      for bladder cancer, comprising 48 with an orthotopic neobladder (26 with an ileal
      and 22 with a colon neobladder) and 37 with an ileal conduit. HRQoL was evaluated
      using the Short Form-36 survey containing 36 questions assessing eight aspects,
      including physical functioning, role-physical functioning, bodily pain, general
      health, vitality, social functioning, role-emotional functioning and mental
      health. RESULTS: The mean follow-up periods for patients with a neobladder (ileal
      and sigmoid) and with an ileal conduit was 45.9 (38.2 and 53.1, respectively) and
      130.9 months, respectively. Scale scores were not affected by the duration of
      follow-up in either group. There was no significant difference in any scale
      scores between the neobladder and ileal conduit groups. However, general health
      and social functioning in both the neobladder and ileal conduit groups appeared
      to be significantly lower than those in the general population in the USA.
      Furthermore, patients with a colon neobladder had a significantly higher score
      for role-emotional functioning than those with an ileal neobladder, while there
      was no significant difference in the remaining seven scores between patients with
      ileal and colon neobladders. CONCLUSIONS: Six of the eight scales of HRQoL were
      favourable in both patients with a neobladder or an ileal conduit, and there was
      no significant difference between these groups. In addition, the HRQoL of
      patients with an orthotopic neobladder (except for role-emotional functioning)
      was unaffected by the segment of the intestine used for neobladder construction.
      Therefore, patients with both types of urinary diversion were generally satisfied
      with their overall health and quality of life.

PMID- 11849153
TI  - Laparoscopic lymph node sampling in locally advanced prostate cancer.
AB  - OBJECTIVE: To assess the role of laparoscopic lymph node sampling in patients
      with locally advanced prostate cancer before radical radiotherapy, and to show
      that the procedure is safe when carried out by urologists with the appropriate
      training. PATIENTS AND METHODS: Patients were selected prospectively using a
      combination of prostate-specific antigen (PSA) level, clinical stage and Gleason
      grade, which predicted a > 20% risk of lymph node metastases. Between October
      1998 and March 2001, 50 patients (mean age 65 years, range 54-78) underwent
      laparoscopic pelvic lymphadenectomy. Age, presenting PSA level, Gleason grade,
      clinical stage, operative time, length of stay, and any adverse events were
      recorded. The histology reports were reviewed for the presence of nodal
      metastases. The selection criteria were compared between the groups with and with
      no nodal metastases. RESULTS: The mean (range) PSA level of the men was 36.8 (4.4
      184) ng/mL and the Gleason grade 6.8 (4-9); 58% had stage T3 disease and 12
      patients (24%) had lymph node metastases. There were no statistically significant
      differences in PSA, Gleason grade or clinical stage between those with positive
      or negative nodes. The mean operative duration was 110 min, although this
      decreased from 133 min for the first 10 cases; one case was converted to an open
      procedure. The median (range) postoperative stay was 1 (1-12) days. There were
      two major (5%) and seven (17%) minor complications. CONCLUSIONS: This study
      confirms that laparoscopic lymph nodes can be sampled safely by urologists with
      experience in laparoscopic surgery. Patients with a significant risk of
      metastases can be selected preoperatively using a combination of PSA, clinical
      stage and Gleason grade. Lymph node sampling in this group is necessary, as there
      is no other method of reliably identifying the subgroup of patients with
      metastatic disease in which radical conformal radiotherapy cannot be justified.

PMID- 11849156
TI  - p53 and bcl-2 immunohistochemistry in preoperative biopsies as predictors of
      biochemical recurrence after radical prostatectomy.
AB  - OBJECTIVE: To evaluate p53 and bcl-2 immunohistochemistry in preoperative
      biopsies and radical prostatectomy specimens, as predictors of biochemical
      recurrence. PATIENTS AND METHODS: Preoperative biopsies from 73 men, and the
      radical prostatectomies from these men and from a further 47 men, were evaluated.
      The serum prostate specific antigen (PSA) level, Gleason score, pathological
      stage and margin involvement were recorded. The immunohistochemical expression of
      p53 and bcl-2 was studied on a representative area of tumour with the highest
      Gleason grade. The median follow-up was 53 months. RESULTS: During the follow-up
      47 of the 120 patients had a biochemical recurrence. Capsular penetration was
      present in 63 (53%) and the surgical margins were positive in 47 (39%). The
      Gleason score was < 7 in 81 (68%) patients; p53 was positive in 40 (66%) of 61
      biopsies and 84 (71%) of 118 prostatectomy specimens. Bcl-2 was positive in eight
      (13%) of 63 biopsies and 20 (17%) of 118 prostatectomies. On multivariate
      analysis the biopsy p53, Gleason score and serum PSA were significant predictors
      of recurrence. On multivariate analysis, capsular penetration, PSA and margin
      status at prostatectomy were significant predictors of recurrence. There was also
      a significant interaction between PSA and margin status. Although univariately
      significant, neither p53 nor bcl-2 featured in the final multivariate model.
      CONCLUSION: Biopsy p53 status significantly predicts recurrence after radical
      prostatectomy, but its low specificity and technical issues suggest that it will
      not be useful in the clinical setting. However, a patient with negative p53 on
      biopsy is likely to have a good prognosis on prolonged follow-up.

PMID- 11849155
TI  - Allogeneic whole-cell vaccine: a phase I/II study in men with hormone-refractory
      prostate cancer.
AB  - OBJECTIVE: To establish the safety and toxicity of an allogeneic human tumour
      cell vaccine in patients with hormone-refractory prostate cancer, and to
      determine any biochemical, immunological or clinical response to vaccination.
      PATIENTS AND METHODS: Sixty patients with hormone-refractory prostate cancer were
      recruited and randomly allocated into four equal groups. Three cell lines (from a
      bank of four) were administered initially every 2 weeks and then monthly, in
      conjunction with the immunostimulant Mycobacterium vaccae (SRL-172), each group
      receiving a different combination of the four cell lines. The patients' serum
      prostate-specific antigen (PSA) levels were monitored regularly, and the immune
      response to the vaccine measured using nonspecific intracellular cytokines and
      specific humoral and cell-mediated assays. RESULTS: The vaccine was safe and well
      tolerated with no major side-effects. Whilst several patients had a decline in
      PSA from the entry level, there was no significant decrease that could be
      attributed solely to the vaccine. However, the immunological data were more
      encouraging, with several patients from each arm of the trial having an increase
      in cytokine production, increases in specific antibodies and evidence of T-cell
      proliferation in response to the vaccinations. CONCLUSION: The failure of the
      vaccine to produce a PSA response in the patients in the trial is not surprising
      considering the stage of the disease. The high PSA levels on entry indicate that
      the burden of disease was probably high and thus this was an extremely
      challenging group of patients in which to try and elicit a response through
      immunotherapy. However, the immunological evidence of a response to the vaccine
      was encouraging and suggests that further exploration of immunotherapy in less
      advanced disease may yield more encouraging clinical responses.

PMID- 11849157
TI  - Improving prostate cancer detection with an extended-core transrectal
      ultrasonography-guided prostate biopsy protocol.
AB  - OBJECTIVE: To investigate whether taking two transition zone (TZ) and four
      lateral peripheral zone (PZ) biopsies in addition to routine parasaggital sextant
      biopsies would improve detection rates in men with suspected prostate cancer.
      PATIENTS AND METHODS: The study included 493 consecutive men (mean age 68.7
      years, sd 8.2) with elevated serum prostate-specific antigen (PSA) levels and/or
      abnormal findings on a digital rectal examination who underwent transrectal
      ultrasonography-guided prostate biopsy. In addition to sextant biopsies, six
      further biopsies were obtained, two from the TZ (mid-gland) and four from the
      lateral PZ (base and mid-gland). Pathological findings for the additional
      biopsies were compared with those of the sextant regions. RESULTS: Prostatic
      adenocarcinoma was diagnosed in 164 of the 493 (33%) men biopsied. Men with
      cancer were older, had smaller prostates and higher median PSA levels than men
      with negative biopsies. Sextant biopsies were positive for cancer in 133 of 164
      (81%) men. All three sets of biopsies were positive in 53 (32%) cases. In 50
      (30%) men both the sextant and lateral PZ biopsies were positive, while in six
      (4%) men, both sextant and TZ biopsies were positive. Thirty-one (19%) tumours
      were not detected by sextant biopsies, 10 (6%) where the lateral PZ biopsies
      alone were positive, 17 (10%) where the TZ biopsies alone were positive and four
      (3%) where both the TZ and lateral PZ together were positive. There were no
      differences in median PSA concentration, total prostate volume or TZ volume
      between men with an isolated TZ cancer and men with cancer elsewhere in the
      prostate. However, 77% of men with TZ cancer had a PSA of > 10 ng/mL, compared
      with 60% of men with cancer at other sites within the prostate (P = 0.015).
      CONCLUSION: An extended-core biopsy protocol significantly improves the detection
      rate for prostate cancer when compared with the standard sextant biopsy protocol
      alone. Routine TZ biopsies should be considered for men with serum PSA levels of
      >10 ng/mL.

PMID- 11849158
TI  - Improving glandular coverage during prostate biopsy using a long-core needle:
      technical performance of an end-cutting needle.
AB  - OBJECTIVE: To compare the technical performance of a 33-mm core-length biopsy
      needle with that of the standard 18 mm needle, as many prostate cancers are
      isoechoic and in large prostates the tissue coverage with the 18 mm needle is
      inadequate. PATIENTS AND METHODS: A 33-mm core length BioPince VSL disposable
      needle (Amedic, Sweden) and a standard TruCut 18 mm needle (Medical Device
      Technology Inc., FL, USA) were used to take prostatic biopsies in two groups of
      15 patients. The following variables were assessed for each group: mean core
      length, core quality, capsular coverage (one or both capsules within the
      specimen), and side-effects in the first week after biopsy (for the BioPince
      group, surveyed using a self-completed questionnaire). The results were compared
      with historical data from a group of 30 patients biopsied using the standard
      needle. RESULTS: For the BioPince and standard groups the mean (sd) core length
      was 19.4 (8.9) and 14.9 (5.1) mm, respectively. Four needles in the BioPince
      group failed to capture a sample, requiring needle replacement. The samples were
      fragmented in 15 of 90 (17%) and 41 of 90 (46%) biopsies in the BioPince and
      standard groups, respectively (P < 0.05). Specimens had both capsules present in
      five of 90 (6%) and four of 90 (4%), respectively. Within 7 days minor bleeding
      was the most common side-effect. Pain after biopsy was the only symptom showing a
      significant difference between the groups, at six of 15 and none (P = 0.001),
      respectively. The incidence of haematuria, haematospermia and rectal bleeding was
      similar in the two groups (P > 0.05), but fever more common (three vs none) in
      the BioPince group (P = 0.06). CONCLUSION: When set at a 33-mm stroke length, the
      BioPince needle increases the mean core length by 30%, with less fragmentation
      than a standard 18 mm needle. However, it has a significant failure rate for
      capture (27% needle replacement rate), slightly greater morbidity (pain and
      possibly fever) and shows no advantage in capsular coverage. Therefore, there are
      shortcomings with this end-cutting needle when used at 33 mm core length.

PMID- 11849159
TI  - Sacral distribution of prostatic lymph nodes visualized on spiral computed
      tomography with three-dimensional reconstruction.
AB  - OBJECTIVE: To evaluate the involvement of sacral lymph nodes in prostatic
      lymphatic drainage, using contemporary radiological imaging techniques. PATIENTS
      AND METHODS: The study included six patients (mean age 61.8 years, range 51-75)
      with suspected prostate cancer. First, an oil-based contrast medium was injected
      into the prostate under transrectal ultrasonographic and fluoroscopic guidance,
      after which a standard ultrasound-guided sextant biopsy was taken. Before
      injecting the contrast medium, and 20 min and 24 h thereafter, the patients
      underwent spiral computed tomography of the pelvic region with three-dimensional
      reconstruction. RESULTS: In all patients the prostate drained via the sacral
      lymphatic region. Compared with the iliac lymphatic drainage system, there were
      fewer and narrower sacral lymph nodes. Prostatic sacral lymph nodes were located
      at S2 to S5, with an emphasis on S3-4. Lymph nodes were detected as presacral and
      in the sacral foramen, suggesting a direct lymphatic connection to the bony
      pelvis. CONCLUSION: These results suggest that sacral prostatic lymphatics are a
      potential route of spread of prostate cancer cells.

PMID- 11849160
TI  - Extraordinarily high rates of male circumcision in South Korea: history and
      underlying causes.
AB  - OBJECTIVE: To investigate the high circumcision rate in South Korea and its rapid
      increase in the short period since its introduction. SUBJECTS AND METHODS: From
      January to December 2000, 5434 South Korean males (or their parents) aged 0-92
      years were interviewed in detail about their circumcision status, their age at
      circumcision, and the possible effect of circumcision on their sexuality. In
      addition, 267 practising medical doctors were surveyed about their basic
      understanding of circumcision and phimosis. RESULTS: Currently the circumcision
      rate for high-school boys is > 90% and for those > 70 years old is < 10%. The
      circumcision rate in 1945 was < 0.1%. When averaged over the whole population,
      the present South Korean circumcision rate is approximately 60%; the rate has
      increased dramatically with time and particularly in the past 20 years, when the
      estimated number of male circumcisions has exceeded the number of male births.
      Although circumcision in South Korea has been strongly influenced by American
      culture, it has never been predominantly neonatal. The age at circumcision has
      continued to decrease and boys are now circumcised at approximately 12 years old.
      Of those who were circumcised long after they had been sexually active, > 80%
      reported no noticeable difference in sexuality, but a man was twice as likely to
      have experienced diminished sexuality than improved sexuality. Of the doctors who
      were surveyed, 41% carried out circumcision but, unlike in America,
      gynaecologists and paediatricians rarely did so. Among the doctors, basic
      knowledge on circumcision and phimosis was generally lacking, regardless of
      whether they practised circumcision or not. Amongst the factors contributing to
      the high circumcision rate was the mistaken notion held by both doctors and the
      general public that circumcision is directly correlated with industrialization
      and general progress of living standards. Many doctors believe the out-dated and
      sometimes controversial benefits of circumcision, i.e. prevention of cervical
      cancer and sexually transmitted diseases, and improved sexuality. Thus the vast
      majority of doctors recommend circumcision regardless of the patient's age. Peer
      pressure was also an important contributing factor. CONCLUSION: South Korea has
      an unusual history of circumcision. The mistaken and out-dated notions about
      circumcision and lack of knowledge of phimosis by physicians seem to be a leading
      contributory factor to the extraordinarily high circumcision rate.

PMID- 11849161
TI  - The migration of Proteus mirabilis and other urinary tract pathogens over Foley
      catheters.
AB  - OBJECTIVE: To examine the ability of organisms that infect the catheterized
      urinary tract to migrate over the surfaces of Foley catheters. MATERIALS AND
      METHODS: In a simple laboratory model, organisms were challenged to migrate
      across sections of hydrogel-coated latex, hydrogel/silver-coated latex, silicone
      coated latex and all-silicone catheters. The sections (1 cm long) were placed as
      bridges in channels between blocks of agar and the test organisms inoculated onto
      the agar adjacent to one side of each bridge. The plates were incubated at 37
      degrees C for 24 h and examined for growth of the test organisms on the agar on
      the other side of the bridges. A collection of swarming, swimming and nonmotile
      species were tested in the model. The relative mobilities of the test organisms
      were expressed as migration indices, calculated as the percentage of tests in
      which bacterial migration was observed over each type of catheter bridge.
      RESULTS: The swarmer cells of Proteus mirabilis and P. vulgaris migrated
      successfully (migration indices of 73-100) over all four types of catheter. The
      migration index of Serratia marcescens swarmers was reduced to 33 over the silver
      coated catheters, but these cells crossed over the other catheter surfaces with
      ease (indices of 100). Pseudomonas aeruginosa was the most mobile of the
      swimming, non-swarming organisms with indices of 70-22, but this group was less
      capable of migration than the swarmers. Indices were 0-33 for nonmotile
      organisms. The mean migration indices for the nine species for each type of
      catheter were 57 (hydrogel-coated latex), 49 (silver/hydrogel-coated latex), 41
      (silicone-coated latex) and 35 (all-silicone). The swarmer cells of P. mirabilis
      moved through populations of Escherichia coli, Klebsiella pneumoniae,
      Staphylococcus aureus and Enterococcus faecalis, and then migrated over sections
      of hydrogel-coated latex catheters with little or no reduction in migration
      index. They were also capable of transporting the nonmotile cells of K.
      pneumoniae and S. aureus over the catheters. The migration index of P. mirabilis
      swarmers was substantially reduced in the presence of Ps. aeruginosa and S.
      marcescens. CONCLUSIONS: Hydrogel coatings facilitate the migration of urinary
      tract pathogens over catheter surfaces. With the exception of S. marcescens, the
      incorporation of silver into the hydrogel did not inhibit migration. Swarmer
      cells were particularly effective at moving over catheters and P. mirabilis
      swarmers were also capable of transporting other species. This suggests that
      inhibitors of swarming could be useful in controlling catheter-associated
      infection and the complications resulting from the spread of bacterial biofilm
      over catheters.

PMID- 11849162
TI  - Prevalence and risk factors of urinary incontinence in young and middle-aged
      women.
AB  - Objective To assess the prevalence of and risk factors for urinary incontinence
      (UI) in young and middle-aged women. Subjects and methods During 1998 the
      prevalence of overall, stress, urge and mixed UI was assessed in women working in
      a French academic hospital. Women (2800) received a questionnaire at the same
      time as their yearly interview with a staff physician in occupational medicine.
      The usual risk factors for constitutional events, i.e. increasing age, obesity
      (defined as a body mass index of > or = 25), obstetric events (pregnancy,
      previous Caesarean delivery, previous vaginal delivery, postpartum incontinence)
      and gynaecological events (hysterectomy) were evaluated. Results Of the 1700
      women (mean age 40.0 years) who returned the questionnaire, 467 (27.5%, 95%
      confidence interval, CI, 25.4-29.7) reported UI, comprising 210 (12.4%, 10.8
      14.0) with stress UI, 28 (1.6%, 1.1-2.4) with urge UI and 229 (13.5%, 11.9-15.2)
      with mixed UI. Thirty-eight women (8.1%) had frequent urinary leakage, comprising
      one (0.5%), four (14.3%) and 33 (14.4%) with stress, urge and mixed UI. The
      prevalence of UI increased significantly with age > or = 40 years, with a
      relative risk (95% CI) of 2.16 (1.86-2.57), and with pregnancy (2.22, 1.71-2.87),
      previous vaginal delivery (2.15, 1.72-2.69), postpartum incontinence (2.57, 2.22
      2.97), and hysterectomy (1.52, 1.11-2.08). Obesity (1.14, 0.99-1.32) and previous
      Caesarean delivery (2.15, 1.72-2.69) did not significantly increase the risk of
      UI. The risk factors for stress UI were age > or = 40 years, pregnancy, previous
      vaginal delivery, postpartum incontinence and hysterectomy, but there was no
      relationship between stress UI and obesity or previous Caesarean delivery.
      Conclusion There was a high prevalence of UI among young adult and middle-aged
      women hospital workers who had easy access to medical resources. Gynaecological
      and obstetric events (pregnancy, particularly previous vaginal delivery and
      hysterectomy) were the most prominent risk factors, especially for stress UI.

PMID- 11849163
TI  - Medical photography: ethics, consent and the intersex patient.

PMID- 11849165
TI  - Calyx to parenchyma ratio in pelvi-ureteric junction obstruction.
AB  - OBJECTIVE: To review the ultrasonography of patients who had undergone
      pyeloplasty for pelvi-ureteric junction (PUJ) obstruction, and document the
      changes in calyceal distension and parenchymal thickness after pyeloplasty, to
      attempt to establish an additional prognostic indicator. PATIENTS AND METHODS:
      Fifty-eight patients who underwent pyeloplasty for PUJ obstruction were assessed
      retrospectively. Pre- and postoperative ultrasonograms were analysed for both
      pyelocaliectasis, graded according to the Society for Fetal Urology criteria, and
      the ratio of the depth of calyces to the thickness of the parenchyma (C/P ratio).
      Patients underwent nuclear medicine renography before and 3 months after
      pyeloplasty. The results were analysed using the paired t-test, Kruskal-Wallis
      test, Spearman's correlation coefficient by rank test and the Mann-Whitney U
      test. RESULTS: There was no significant difference in hydronephrosis grade before
      and after surgery (P < 0.05) but there was a significant difference in the C/P
      ratios (P < 0.01). There was no correlation between C/P ratios and the results of
      diuresis renography. CONCLUSION: Hydronephrosis as measured by an estimate of
      pelvic volume is an insensitive marker of improvement after pyeloplasty. Reduced
      calyceal distension correlates well with other favourable prognostic indicators.
      Therefore, the C/P ratio may be an additional indicator of the appropriateness of
      surgical intervention, and should be the subject of further study.

PMID- 11849166
TI  - Prenatal diagnosis of cloacal anomalies.
AB  - OBJECTIVE: To evaluate prenatal diagnosis in facilitating prenatal counselling
      and planning optimal perinatal care for persistent cloaca, a complex malformation
      with variable presentation and a difficult reconstructive challenge for the
      paediatric urologist and surgeon. PATIENTS AND METHODS: The prenatal records of
      six patients with a suspected prenatal diagnosis of cloacal anomaly, subsequently
      confirmed on delivery, were reviewed. All had serial prenatal ultrasonograms.
      Fetal medicine and paediatric surgical specialists were present for the scans and
      counselled the parents jointly. RESULTS: The diagnosis was made at 19-33 weeks of
      gestation; all fetuses had a cystic structure arising from the pelvis and
      bilateral hydronephrosis, with a poorly visualized fetal bladder in most. Other
      prenatal features included transient fetal ascites, oligohydramnios, ambiguous
      genitalia and growth retardation. Female karyotype was confirmed in all cases by
      amniocentesis. Diagnosis was aided in two patients by fetoscopy and in another by
      magnetic resonance imaging. CONCLUSIONS: Cloacal anomalies can be diagnosed
      prenatally and should be considered in any female fetus presenting with bilateral
      hydronephrosis, a poorly visualized bladder and a cystic lesion arising from the
      pelvis. Prenatal diagnosis allows time for parental counselling and planning of
      the delivery at a centre equipped with neonatal intensive-care and paediatric
      surgical facilities.

PMID- 11849167
TI  - A single-centre long-term outcome analysis of artificial urinary sphincter
      placement in children.
AB  - OBJECTIVE: To retrospectively evaluate the outcome of artificial urinary
      sphincter (AUS) placement in 79 children, with a mean follow-up of 12.5 years.
      PATIENTS AND METHODS: A total of 89 children had an AUS placed between 1977 and
      1994; complete data were obtained for 79 (63 boys and 16 girls). The indication
      for AUS placement was urinary incontinence caused by sphincteric deficiency with
      a stable bladder. Before and after surgery, all patients underwent
      ultrasonography, voiding cysto-urethrography and urodynamics. Logistic regression
      was used to assess the factors influencing the outcome. RESULTS: The mean (range)
      age at surgery was 11.7 (3-18) years. The cause of incontinence was a neuropathic
      bladder in 74 patients and bladder exstrophy in five. At a mean (range) follow-up
      of 12.5 (5-22) years, 63 of 79 patients (80%) had an intact AUS. The AUS was
      removed in 16 patients (20%) because of erosion at a mean (range) of 5.6 (1-11)
      years after insertion; there were 0.035 revisions per patient-year. Of 63
      patients with an AUS in place, 57 (90%) are completely dry and 36 (57%) are using
      clean intermittent catheterization. Thirteen patients (20%) developed bladder
      instability during the follow-up, which was managed by anticholinergics in eight,
      spinal cord de-tethering in three and enterocystoplasty in two. Hydronephrosis
      occurred in 12 of 126 renal units (10%) that improved after enterocystoplasty or
      anticholinergics. The overall 10-year survival of the AUS was 79% (78% for early
      models and 80% for the AMS800); the survival was not affected by age, sex, model,
      previous bladder neck surgery, augmentation cystoplasty or intermittent
      catheterization. Bladder exstrophy was associated with lower AUS survival, as
      four of the five patients affected had the AUS removed secondary to erosion (P =
      0.014). CONCLUSION: In children the AUS has a 79% 10-year survival and gives a
      90% continence rate. Bladder instability after AUS placement can be managed with
      anticholinergics or enterocystoplasty. The AUS is not a justifiable treatment
      option for patients with bladder exstrophy.

PMID- 11849168
TI  - Continent catheterizable conduits: which stoma, which conduit and which
      reservoir?
AB  - OBJECTIVE: To assess the outcome of the various methods used in creating
      continent catheterizable conduits. PATIENTS AND METHODS: The case notes were
      reviewed from 89 patients who underwent the formation of 112 continent
      catheterizable conduits. RESULTS: Sixty-five conduits were Mitrofanoff and 47
      were antegrade colonic enema (ACE); 21 patients had both. At a mean follow-up of
      34 months, 95 (85%) conduits were still in use. There was no difference in
      complications between the Mitrofanoff and ACE conduits; 109 (97%) conduits were
      continent and stomal stenosis occurred 35 (31%). There was no significant
      difference relating to the conduit used, the reservoir, the stoma type or the
      stoma site. Only 39% of patients required no revisional surgery. CONCLUSION:
      Although urinary and fecal continence can be achieved in most patients there is a
      high burden of complications and revisional surgery. All patients should be
      counselled accordingly.

PMID- 11849169
TI  - Tubularized incised-plate urethroplasty for proximal hypospadias.
AB  - OBJECTIVE: To report the experience of one surgeon using tubularized incised
      plate (TIP) urethroplasty to repair proximal hypospadias in a consecutive series
      of boys. PATIENTS AND METHODS: The records of 33 consecutive patients with
      midshaft to scrotal hypospadias undergoing TIP repair by one surgeon were
      reviewed. Dorsal plication was used as necessary for penile straightening, to
      preserve the urethral plate. Standard TIP urethroplasty was undertaken, and the
      follow-up included the selective use of neourethral calibration and urethroscopy.
      RESULTS: Plication was necessary in 18 (55%) patients. The incised plate had a
      supple appearance in all but two boys. The mean (range) follow-up was 9 (1-48)
      months and included calibration in 16 (48%) and urethroscopy in 13 (39%)
      patients. Complications were noted in 11 (33%) boys, of whom seven (21%)
      developed small fistulae. The two patients in whom the incised plate appeared
      unhealthy had dehiscence of the repair and contracture of the neourethra with
      recurrent penile curvature, respectively. There was one meatal stenosis and one
      short neourethral stricture. CONCLUSIONS: TIP urethroplasty can be used to repair
      proximal hypospadias in the absence of severe penile curvature, and if the
      incised urethral plate has a supple appearance. As with distal hypospadias
      repair, the procedure creates a normal-appearing penis with a slit-like meatus.

PMID- 11849170
TI  - Regular dilatation is unnecessary after tubularized incised-plate hypospadias
      repair.
AB  - OBJECTIVE: To determine if patients who undergo tubularized incised-plate (TIP)
      urethroplasty need regular dilatation to prevent neourethral strictures or meatal
      stenosis. PATIENTS AND METHODS: The follow-up of two consecutive series of
      patients who underwent primary TIP hypospadias repair by one surgeon was
      reviewed. The first 72 patients (group 1) had periodic neourethral calibrations
      for 1 year after repair, while the next 62 patients (group 2) had no routine
      dilatation, except for six patients (10%) in whom the meatus appeared to be
      small. Urethroscopy was performed in both groups at the time of fistula repair,
      skin revisions or during anaesthesia for unrelated procedures. RESULTS: There was
      no evidence of scarring in group 1; one case of meatal stenosis and one
      neourethral stricture were detected in group 2. The difference in outcome was not
      statistically significant (P = 0.4). Overall, the incidence of meatal stenosis
      was low (0.7%) and comparable with most recent series in which postoperative
      calibration was not used routinely. CONCLUSION: Dilatation of the neourethra is
      unnecessary after TIP urethroplasty. Calibration or uroflowmetry 6 months after
      surgery may be useful to detect subclinical obstruction.

PMID- 11849171
TI  - Tubularized incised-plate urethroplasty for hypospadias reoperation.
AB  - OBJECTIVE: To review our preliminary results of tubularized incised-plate (TIP)
      urethroplasty for reoperative hypospadias repair. PATIENTS AND METHODS: The study
      comprised 15 patients, of whom eight had undergone a previous repair by
      techniques that included incision into the midline of the urethral plate, while
      in the remaining seven the midline of the plate had been left undisturbed. The
      meatus at reoperation was subcoronal or on the distal shaft in all but one boy,
      who had a midshaft hypospadias. All had previously undergone one attempt at
      hypospadias repair, except for one patient presenting after two failed 'meatal
      advancement and glanuloplasty incorporated' procedures. The TIP repair was
      undertaken as described for primary surgery, except that the dorsal dartos flaps
      for interposition between the neourethra and skin closure were available less
      often. RESULTS: TIP resulted in a functional neourethra and a cosmetically normal
      meatus in 13 of the 15 patients. One boy healed with a slightly rounded meatus
      and the other had wound dehiscence; fistulae developed in another two boys,
      giving three patients with complications. The fistulae occurred in boys whose
      original surgery did not include urethral plate incision, while the dehiscence
      was in a patient with partial excision of the plate during previous tubularized
      preputial flap repair. CONCLUSIONS: TIP urethroplasty can potentially be used for
      hypospadias reoperation. Previous incision of the urethral plate was not a
      contraindication in these selected cases in which the plate appeared supple.
      However, TIP repair should be avoided in repeat hypospadias surgery if the plate
      has been resected or is obviously scarred.

PMID- 11849172
TI  - Management of severe hypospadias using Glassberg's modification of the Duckett
      repair.
AB  - OBJECTIVE: To assess the effectiveness of Glassberg's modification of Duckett's
      technique in the surgical correction of severe hypospadias. PATIENTS AND METHODS:
      The case notes of 24 boys who underwent hypospadias repair using this technique
      were reviewed, noting the severity of the lesion, the method of repair and the
      clinical outcome. RESULTS: One operation was required in 14 (58%) of patients;
      complications requiring further surgery occurred in 10 boys (42%). CONCLUSION:
      This technique allows a single-stage procedure when otherwise a two-stage
      procedure would be necessary.

PMID- 11849173
TI  - Outcome of hypospadias fistula repair.
AB  - Objectives To examine the long-term results of hypospadias fistula repair, the
      factors involved in recurrence and the outcome in cases where this has occurred.
      Patients and methods The study comprised 113 children undergoing urethrocutaneous
      fistula repair between 1984 and 1996. Most of the fistulae were closed in two to
      three layers, with or without a transpositional skin flap. Tunica vaginalis or a
      scrotal dartos flap was used in patients with inadequate vascularized tissue
      adjacent to the fistula. Success rates were calculated for each attempt at
      fistula repair until the patient was cured. Results The median (range) age at
      primary fistula repair was 40 (18-169) months and the median follow-up after the
      most recent repair 7.5 (2.3-17) years. The overall success rate of primary
      fistula repair was 71%. Fistulae which were >2 mm (11 of 21, 52%) were more
      likely to recur than were those < or = 2 mm (22 of 92, 24%). Recurrence did not
      relate to the initial form of hypospadias repair, to the means of skin closure
      nor, with the exception of multiple lesions, to the location of the fistula. The
      success rates of subsequent repairs were 70% at the second and 50% at the third,
      fourth and fifth repairs. One child was cured at the sixth attempt. The use of
      tunica vaginalis or scrotal dartos as a 'waterproofing' layer was limited to the
      third or subsequent repairs and was successful in five of six cases. Conclusion A
      simple layered closure with or with no transpositional skin flap is effective in
      71% of repairs. For recurrent fistulae, tissues from an unscarred area (tunica
      vaginalis or scrotal dartos layer) should be used to cover the fistula.

PMID- 11849174
TI  - Over-expression of apoptosis-related proteins contributes to muscular damage in
      the obstructed ureter of the rat.
AB  - OBJECTIVE: To determine the role of apoptosis-related proteins (Myc, Bax, Bcl-2,
      and Bcl-X(L)) in muscular damage in obstructed rat ureters. MATERIALS AND
      METHODS: The in situ end-labelling of DNA fragments and the expression of
      apoptosis-related proteins were assessed, using immunohistochemistry, in 54
      female Sprague-Dawley rats in which unilateral ureteric obstruction was caused by
      ureteric ligation. RESULTS: The severity of ureteric damage increased during the
      period of obstruction. Apoptotic cells and the expression of Bax were detected in
      the smooth muscle layer from 14 days after ligation. The percentage of apoptotic
      cells and the expression of Bax in the smooth muscle layer increased and reached
      a peak 21 days after ligation, and then declined. The expression of Myc was also
      detected in the smooth muscle layer 14 days after ligation but reached a peak at
      28 days. The expressions of Bcl-2 and Bcl-X(L) in the smooth muscle layer were
      only detected 21 and 28 days after ligation. The numbers of apoptotic cells in
      the smooth muscle layer correlated significantly with the expressions of Myc and
      Bax (r = 0.7360 and 0.7432, respectively; both P < 0.005), and with the
      expression index of Bax/Bcl-2 and Bax/Bcl-X(L) (r = 0.8909 and 0.8592,
      respectively; both P < 0.001). CONCLUSIONS: Apoptosis-related proteins might be
      important in regulating cell apoptosis in ureteric damage during the development
      of obstructive uropathy.

PMID- 11849175
TI  - Gubernacular development in Mullerian inhibiting substance receptor-deficient
      mice.
AB  - OBJECTIVE: To determine, in mice with disrupted Mullerian inhibiting substance
      (MIS) receptor genes, whether MIS affects gubernacular development; MIS causes
      Mullerian duct regression and is proposed to be involved in the first stage of
      testicular descent, because gubernacular development is abnormal in humans with
      persistent Mullerian duct syndrome. MATERIALS AND METHODS: Ten wild-type, 11
      heterozygotic and 12 homozygotic mice for MIS receptor mutations were killed at
      17.5 or 18.5 days after conception or at birth, to provide serial sagittal
      sections of the pelvis. The amount of cremaster muscle, mitotic bodies in the
      gubernacular bulb, and gubernacular size were quantified by computer analysis
      (four mice/group). RESULTS: Mullerian ducts were present in the homozygous
      mutants, partially present in the heterozygotes and absent in the wild-type
      controls. All mice had descended testes. The cremaster muscle was significantly
      less developed in homozygous mutants than in wild-type controls (P < 0.001) and
      heterozygotes (P < 0.01) at birth. The mitotic index between the gubernacula of
      all groups was indistinguishable. There was no statistical difference in
      gubernacular area amongst the groups. Poor cremaster muscle development in
      homozygous mutants gave the muscle a loose mesenchymal appearance. CONCLUSIONS:
      Although there was an observable effect on cremaster muscle development in these
      mutant mice, gubernacular development and testicular descent were otherwise
      normal, and thus there must be other reasons for the observed differences in
      humans with persistent Mullerian duct syndrome.

PMID- 11849176
TI  - Bladder cancer cell implantation in reconstructed bladder in vitro: a model of
      tumour recurrence.
AB  - OBJECTIVE: To evaluate the involvement of umbrella cells in tumour adhesion and
      growth, by examining whether human urinary bladder carcinoma cells (HUBCC) can
      grow on reconstructed urinary bladder mucosa in vitro, as the implantation of
      tumour cells after resection is thought to be a cause of bladder tumour
      recurrence. MATERIALS AND METHODS: Normal transitional epithelial cells isolated
      from porcine bladder were cultured on reconstructed lamina propria using
      fibroblasts in type I collagen gel. The urothelium thus reconstructed was
      artificially injured either by a scalpel or by dilute acid, after which
      transitional epithelial cells began to grow in a stratified fashion within a few
      days of culture. A HUBCC line (HT-1197) was seeded onto this impaired mucosa to
      determine whether the cells could become implanted. Cultured cells on the
      reconstructed mucosa were evaluated by histological observation of vertical
      paraffin sections. RESULTS: The inoculated transitional epithelial cells grew in
      a stratified fashion and closely resembled urothelium in vivo. The superficial
      cells that were in contact with the medium solution differentiated into umbrella
      cells. HUBCC were unable to adhere to reconstructed mucosa which had not been
      injured, but these cells could adhere to and become implanted on the
      reconstructed mucosa after it had been injured either by a scalpel or by dilute
      acid. After acid injury, only the surface-covering cells were removed
      sporadically, while the lower epithelial cell layer remained intact. The bladder
      cancer cells adhered to and proliferated within these stripped regions.
      CONCLUSION: These results suggest that the urothelium, especially umbrella cells,
      seems to be important in preventing the adhesion and growth of urinary bladder
      tumour cells.

PMID- 11849178
TI  - The pudendal thigh fasciocutaneous flap to cover deep perineal defects, combined
      with reconstruction of the posterior urethra.

PMID- 11849177
TI  - Prognostic significance of tumour angiogenesis in schistosoma-associated
      adenocarcinoma of the urinary bladder.
AB  - OBJECTIVE: To report on tumour angiogenesis and its relationship with
      morphological variables and prognosis in adenocarcinoma of the urinary bladder
      associated with schistosomiasis. PATIENTS AND METHODS: Fifty-five vesical
      adenocarcinomas were evaluated from 30 men and 25 women (mean age 47.2 years, sd
      8.7, range 30-65) who were followed up after radical cystectomy and urinary
      diversion for a mean (sd, range) of 61 (43.5, 2.7-159.5) months. Vessels were
      stained immunohistochemically using an antibody to the platelet endothelial cell
      adhesion molecule CD31. Microvessels were counted in active areas of angiogenesis
      within the tumours (at x250) and the microvessel density (MVD) quantified using
      the mean of three counts. Treatment failure was defined as death from cancer or
      the development of local recurrence or distant metastasis. Kaplan-Meier survival
      curves and Cox's proportional hazard model were used to assess survival. RESULTS:
      The overall 5- and 10-year survival rates were 57% and 51%, respectively. The
      presence of lymph node metastasis and high mean vascular density (> 26) were
      significantly associated with a poor prognosis. The 5-year survival for patients
      with negative lymph nodes was 66% while no patients with positive nodes survived
      for 5 years (P < 0.001); the survival was 72% for patients with a low MVD and 33%
      for those with a high MVD (P = 0.0016). From individual results plotted against
      vascularity in lymph node-negative patients, there was a significantly better
      outcome for those with a low MVD (< or = 26; P = 0.0099); this significance was
      maintained on multivariate analysis. However, there was no significant
      relationship between angiogenesis and the different clinicopathological factors
      apart from the grade (P = 0.03); tumour stage, grade and DNA profile had no
      significant effect on survival in these patients. CONCLUSIONS: These findings
      suggest that assessing angiogenesis using the MVD provides an independent
      predictor of survival in patients with adenocarcinoma of the urinary bladder.

PMID- 11849179
TI  - Pyonephrosis and urinary retention secondary to a large Gartner's duct cyst
      associated with single ectopic ureter in a pregnant woman.

PMID- 11849180
TI  - Fowler's syndrome: cause or consequence of insulin resistance?

PMID- 11849182
TI  - Editor's Comment.

PMID- 11849183
TI  - Environmental influences on male reproduction.

PMID- 11849185
TI  - Intracorporeal lithotripters: selecting the optimum machine.

PMID- 11849184
TI  - Postnatal management of antenatal hydronephrosis.

PMID- 11849186
TI  - Open vs laparoscopic donor nephrectomy in renal transplantation.

PMID- 11849189
TI  - Pharmacogenetics of asthma.
AB  - Recent advances in the extent of knowledge regarding interindividual genetic
      variation in drug treatment targets and drug metabolizing enzymes has resulted in
      studies designed to assess the contribution of genetic variability to treatment
      response in a range of diseases. This review describes the current state of
      knowledge of genetic variability in key airway targets important in the treatment
      of asthma. Whilst the genes coding for some key treatment targets contain little
      polymorphic variation (e.g. the muscarinic M2 and M3 receptors) other genes whose
      products are important targets in the treatment of asthma contain extensive
      genetic variation. The best examples of the latter are the beta2-adrenoceptor and
      the 5-lipoxygenase genes. Genetic variability in both of these genes may account
      in part for interindividual variability in treatment response. Finally, a number
      of key targets within the airways remain to be adequately screened for
      polymorphic variation.

PMID- 11849190
TI  - Distribution of venlafaxine and its O-desmethyl metabolite in human milk and
      their effects in breastfed infants.
AB  - AIMS: To characterize milk/plasma (M/P) ratio and infant dose, for venlafaxine
      (V) and its O-desmethyl metabolite (ODV), in breastfeeding women taking
      venlafaxine for the treatment of depression, and to determine the plasma
      concentration and effects of these drugs in their infants. METHODS: Six women
      (mean age 34.5 years, mean weight 84.3 kg) taking venlafaxine (median dose 244 mg
      day(-1), range 225-300 mg day(-1)) and their seven infants (mean age 7.0 months,
      mean weight 7.3 kg) were studied. V and ODV in plasma and milk were measured by
      high-performance liquid chromatography over a 12 h dose interval at steady-state.
      Infant exposure was estimated as the product of estimated milk production rate
      (0.15 l kg(-1)day(-1)) and average drug concentration in milk, normalized to body
      weight and expressed as a percentage of the weight-adjusted maternal dose.
      RESULTS: Mean M/PAUC values of 2.5 (range 2.0-3.2) and 2.7 (range 2.3-3.2) were
      calculated for V and ODV, respectively. The mean maximum concentrations (95% CI)
      of V and ODV in milk were 1161 (95% CI, 588, 1734) microg l(-1) and 796 (362,
      1230) microg l(-1). Mean infant exposure was 3.2% (1.7, 4.7%) for V and 3.2%
      (1.9, 4.9%) for ODV (as V equivalents). V was detected in the plasma of one out
      of seven infants studied (5 microg l(-1)), while ODV was detected in four of the
      infants, at concentrations ranging from 3 to 38 microg l(-1). All of the infants
      in the study were healthy, as reported by their mothers and/or by clinical
      examination on the study day. CONCLUSIONS: The concentrations of V and ODV in
      breast milk were 2.5 and 2.7 times those in maternal plasma. The mean total drug
      exposure (as venlafaxine equivalents) of the breastfed infants was 6.4% (5.5
      7.3%), which is below the 10% notional level of concern. There were no adverse
      effects in any of the infants. The data support the use of V in breastfeeding.
      Nevertheless, since low concentrations of ODV were detected in the plasma of four
      out of the seven infants studied, we recommend breastfed infants should be
      monitored closely. Each decision to breast feed should be made as an individual
      risk:benefit analysis.

PMID- 11849191
TI  - The pharmacokinetic properties of intramuscular artesunate and rectal
      dihydroartemisinin in uncomplicated falciparum malaria.
AB  - AIMS: To obtain pharmacokinetic data for artesunate (ARTS) and its active
      metabolite dihydroartemisinin (DHA) following i.m. ARTS and rectal DHA
      administration. METHODS: Twelve Vietnamese patients with uncomplicated falciparum
      malaria were randomized to receive either i.v. or i.m. ARTS (120 mg), with the
      alternative preparation given 8 h later in an open crossover design. A further 12
      patients were given i.v. ARTS (120 mg) at 0 h and rectal DHA (160 mg) 8 h later.
      RESULTS: Following i.v. bolus, ARTS had a peak concentration of 42 microm (16 mg
      l(-1), elimination t1/2 = 3.2 min, CL = 2.8 l h(-1) kg(-1) and V = 0.22 l kg(-1)
      . The Cmax for DHA was 9.7 microm (2.7 mg l(-1) ), t1/2 = 59 min, CL = 0.64 l h(
      1) kg(-1) and V = 0.8 l kg(-1) . Following i.m. ARTS, Cmax was 2.3 microm (3.7 mg
      l(-1)), the apparent t1/2 = 41 min, CL = 2.9 l h(-1) kg(-1) and V = 2.6 l kg(-1).
      The relative bioavailability of DHA was 88%, Cmax was 4.1 microm (1.16 mg l(-1))
      and t1/2 = 64 min. In the rectal DHA study, relative bioavailability of DHA was
      16%. CONCLUSIONS: For patients with uncomplicated falciparum malaria i.m. ARTS is
      a suitable alternative to i.v. ARTS, at equal doses. To achieve plasma DHA
      concentrations equivalent to parenteral administration of ARTS, rectal DHA should
      be given at approximately four-fold higher milligram doses. Further studies are
      needed to determine whether these recommendations can be applied to patients with
      severe malaria.

PMID- 11849192
TI  - The impact of antihypertensive drug groups on urinary albumin excretion in a non
      diabetic population.
AB  - AIMS: Microalbuminuria (30-300 mg 24 h-1) is recognized to be independently
      associated with renal and cardiovascular risk. Antihypertensives may lower
      microalbuminuria. We questioned whether the use of different antihypertensive
      drug classes in general practice influences microalbuminuria as related to blood
      pressure in nondiabetic subjects. METHODS: To study this, we used the data from
      6836 subjects of an on-going population based study, focused on the meaning of
      microalbuminuria (PREVEND). Odds ratios, adjusted for age, sex, blood pressure,
      cholesterol level, smoking and the use of other antihypertensive or
      cardiovascular drugs, were calculated to determine the association of drug groups
      with microalbuminuria. Influence of antihypertensives on the relation between
      blood pressure and (log) urinary albumin excretion was determined by comparing
      linear regression lines. RESULTS: Microalbuminuria was significantly associated
      with the use of dihydropyridine calcium channel blockers (odds ratio: 1.76 [1.22
      2.54]), but not with other antihypertensive drug groups. The linear regression
      line of the relation between blood pressure and (log) urinary albumin excretion
      was significantly steeper (P = 0.0047) for users of calcium channel blockers, but
      not for other antihypertensives, compared with subjects using no
      antihypertensive. Users of a combination of renin-angiotensin system inhibitors
      and diuretics however, had a less steep regression line (P = 0.037). CONCLUSIONS:
      This study suggests a disadvantageous effect of dihydropyridine calcium channel
      blockers on microalbuminuria compared with other antihypertensive drug groups.
      Thus, if microalbuminuria is causally related to an increased risk for
      cardiovascular morbidity and mortality, dihydropyridines do not seem to be agents
      of choice to lower blood pressure. Furthermore, the combination of renin
      angiotensin system inhibition and diuretics seems to act synergistically.

PMID- 11849193
TI  - Effect of aspirin on vasodilation to bradykinin and substance P in patients with
      heart failure treated with ACE inhibitor.
AB  - AIMS: We wanted to examine some of the mechanisms by which aspirin might be
      responsible for counteraction of the effects of ACE inhibitors. Aspirin has been
      reported to counteract the effects of ACE inhibitors in patients with heart
      failure. Despite this, there is little evidence on what the mediator of such an
      effect might be, although there is some evidence to implicate bradykinin and,
      perhaps, substance P. METHODS: Twelve patients with congestive heart failure
      treated with an ACE inhibitor were studied on two occasions, after abstaining
      from aspirin for 14 days, and after 14 days of aspirin 150 mg once daily. Forearm
      blood flow was measured by venous occlusion plethysmography during intrabrachial
      infusions of bradykinin and substance P, before and after intrabrachial aspirin.
      RESULTS: Bradykinin caused profound vasodilation (peak 390%, 95% confidence
      intervals (CI) 300, 480%; P < 0.01), substance P slightly less (peak 222%, 95% CI
      162, 283%; P < 0.01). Intra-brachial aspirin had no effect on its own. The
      response to bradykinin was unchanged by intrabrachial aspirin (peak 404%, 95% CI
      304, 504%) or oral aspirin (peak 320%, 95% CI 209, 431%; P = 0.2). The response
      to substance P was unchanged by intrabrachial aspirin (peak 226%, 95% CI 171,
      281%) or oral aspirin (peak 220%, 95% CI 142, 297%; P = 0.86). CONCLUSIONS:
      Aspirin has no effect on the vasodilator response to bradykinin and substance P
      in patients with heart failure treated with an ACE inhibitor. Neither bradykinin
      nor substance P is likely to contribute to the reported interaction between
      aspirin and ACE inhibitors.

PMID- 11849194
TI  - A new laser pain threshold model detects a faster onset of action from a liquid
      formulation of 1 g paracetamol than an equivalent tablet formulation.
AB  - AIMS: To discover whether a new infra-red laser method could detect a change in
      pain threshold after as mild an analgesic as paracetamol and whether an
      effervescent liquid formulation produced a faster onset of action than tablets.
      METHODS: This double-blind, placebo controlled randomized study used a portable,
      infra-red laser to measure "first pain" thresholds on the nondominant forearm in
      12 normal volunteers before and after 1 g of paracetamol or placebo. The mean of
      six recordings was determined three times before dosing, the first being used as
      a familiarization procedure, and 14 times after dosing. RESULTS: We detected a
      small (2%), statistically significant difference in pain threshold between a
      liquid formulation of paracetamol and placebo at 30 and 60 min (P = 0.004 and P =
      0.001), but not between tablets and placebo. Liquid also increased the threshold
      significantly compared with tablets at 60 min (P = 0.01). CONCLUSIONS: To detect
      such a small increase in pain threshold requires a highly consistent measure and
      the coefficient of variation was 2% for the study overall, surprisingly low for a
      subjective phenomenon. The reasons for this include minimizing reflectance by
      blacking the skin, using a nonhairy site, averaging six data points at each
      sample time and controlling closely the ambient conditions and the subjects'
      preparation for studies.

PMID- 11849195
TI  - Pharmacokinetics and anticonvulsant effects of diazepam in children with severe
      falciparum malaria and convulsions.
AB  - AIMS: Convulsions are a common complication of severe malaria in children and are
      associated with poor outcome. Diazepam is used to terminate convulsions but its
      pharmacokinetics and pharmacodynamics have not been studied in this group.
      Accordingly, we carried out a comparative study of the pharmacokinetics of
      intravenous (i.v.) and rectal (p.r.) diazepam. METHODS: Twenty-five children with
      severe malaria and a convulsion lasting >5 min were studied. Sixteen children
      received diazepam intravenously (i.v.; 0.3 mg kg(-1)) and nine rectally (p.r.;
      0.5 mg kg(-1)). Plasma diazepam concentrations were measured by reversed phase
      high-performance liquid chromatography. The duration of convulsions, depth of
      coma, respiratory and cardiovascular parameters were monitored. RESULTS: Median
      maximum plasma diazepam concentrations of 634 (range 402-1507) ng ml(-1) and 423
      (range 112-1953) ng ml(-1) were achieved at 5 and 25 min following i.v. and p.r.
      administration, respectively. All patients except three (one i.v. and two p.r.)
      achieved plasma diazepam concentration >200 ng ml(-1) within 5 min. Following
      p.r. administration, plasma diazepam concentrations were more variable than i.v.
      administration. A single dose of i.v. diazepam terminated convulsions in all
      children but in only 6/9 after p.r. administration. However, nine children
      treated with i.v. and all those treated with p.r. diazepam had a recurrence of
      convulsions occurring at median plasma diazepam concentrations of 157 (range: 67
      169) and 172 (range: 74-393) ng ml(-1) , respectively. All the children in the
      i.v. and four in the PR diazepam group who had recurrence of convulsions required
      treatment. None of the children developed respiratory depression or hypotension.
      CONCLUSIONS: Administration of diazepam i.v. or p.r. resulted in achievement of
      therapeutic concentrations of diazepam rapidly, without significant cardio
      respiratory adverse effects. However, following p.r. administration, diazepam did
      not terminate all convulsions and plasma drug concentrations were more variable.

PMID- 11849196
TI  - Pharmacodynamic effect of continuous vs intermittent dosing of dofetilide on QT
      interval.
AB  - AIMS: To investigate the pharmacokinetics and pharmacodynamics of dofetilide 1 mg
      twice daily continuously for 24 days compared with intermittent single dose
      treatments. METHODS: A randomized, single-blinded, placebo-controlled, parallel
      group, multiple-dose study design was utilized. Healthy male volunteer subjects
      were randomized into three groups. Group 1 received dofetilide 1.0 mg twice daily
      for 23 days and once on day 24. Group 2 received matching placebo capsules under
      the same regimen as group 1. Group 3 received a single dose of dofetilide 1.0 mg
      on days 1, 5, 10, 17, and 24 with identical placebo capsules administered at all
      other times to match the dosing pattern of the other groups. RESULTS: Continuous
      administration of dofetilide resulted in the achievement of steady-state
      concentrations by day 5. Pharmacokinetic parameters following intermittent
      treatment showed no accumulation. Maximum daily QTc interval (mean +/- s.e. mean)
      increased in response to continuous twice-daily dofetilide from baseline (373 +/-
      5) to day 2 (453 +/- 9) but thereafter decreased slightly, but not beyond day 5,
      by which time the mean maximum QTc was 440 +/- 7 ms. In contrast, single doses of
      dofetilide in the intermittently treated group led to reproducible increases in
      QTc. Thus mean (+/- s.e. mean) maximum QTc increased from a baseline of 387 +/- 7
      467 +/- 14, 467 +/- 18, 469 +/- 14 and 458 +/- 10 ms on days 5, 10, 17 and 24,
      respectively. In view of the pharmacokinetic accumulation on continuous dosing,
      the attenuation of responsiveness is best represented by the slope of the QTc vs
      plasma concentration relationship. In the continuously treated group, an initial
      decrease in the value of the mean slope between day 1 (14.2 +/- 1.7 ms/ng ml(-1))
      and day 5 (9.1 +/- 0.8 ms/ng ml(-1)) did not progress beyond day 5. The mean
      difference in slopes (95% CI) between the intermittent and continuously treated
      groups were 4.4 (1.3, 7.4) on day 5, 4.9 (1.6, 8.2) on day 10, 5.2 (1.1, 9.2) on
      day 17 and 4.4 (0.4, 8.4) on day 24. CONCLUSIONS: With continuous twice-daily
      administration the QT interval responsiveness to dofetilide is greater after the
      first dose than it is at steady state. After day 5 the relationship between
      dofetilide plasma concentration and its QT interval effect is predictable and
      stable over time.

PMID- 11849197
TI  - The effects of an oral contraceptive containing ethinyloestradiol and norgestrel
      on CYP3A activity.
AB  - AIMS: To examine the effects of an oral contraceptive containing
      ethinyloestradiol and norgestrel on intestinal and hepatic CYP3A activity using
      midazolam as a probe substrate. METHODS: In a nonblinded sequential study, nine
      healthy women received simultaneous doses of intravenous midazolam (0.05 mg kg(
      1)) and oral 15N3-midazolam (3 mg) on days 0, 4, 6, 8, and 14. On study day 5,
      Ovral(50 microg ethinyloestradiol/500 microg norgestrel) was administered for 10
      days. Serum and urine samples were assayed for midazolam, 15N3-midazolam and
      metabolites by liquid chromatography-mass spectrometry. A Digit Symbol
      Substitution Test (DSST) was used to assess changes in the pharmacodynamic
      activity of midazolam. RESULTS: Moderate (% CV 26-46) interindividual variability
      in the pharmacokinetics of midazolam were observed. Compared with baseline,
      AUC(0,infinity)iv ratios (95% CIs) after 2, 4, and 10 days treatment with OC were
      89% (79, 101), 96% (85, 109), and 88% (77, 99), respectively. The
      AUC(0,infinity)oral ratios (95% CIs) were 101% (82, 125), 105% (85, 130), and
      114% (92, 141), respectively, after 2, 4, and 10 days OC treatment compared with
      baseline. Concomitant administration of the oral contraceptive, Ovral for 2, 4 or
      10 days did not significantly alter the area under the curve, clearance, or half
      life of midazolam after either oral or intravenous administration. No alterations
      in pharmacodynamic effects of midazolam were observed between treatment days.
      Mean DSST scores strongly correlated with mean total midazolam blood
      concentrations (r = -0.936). CONCLUSIONS: Administration of Ovral for 10 days had
      no impact on intestinal or hepatic CYP3A activity as determined by midazolam
      metabolism.

PMID- 11849198
TI  - St Johns wort increases expression of P-glycoprotein: implications for drug
      interactions.
AB  - AIMS: St John's Wort (SJW) is widely used in the treatment of depression but
      concerns have been raised about its potential to interact with other drugs. Co
      administration with SJW has resulted in significant reductions in trough plasma
      concentrations of indinavir and cyclosporin [1, 2]. Induction of cytochrome P450
      3A4 (CYP3A4) has been implicated as the most likely interaction mechanism.
      However, the magnitude of the interaction seen in clinical practice is greater
      than that predicted by in vitro studies suggesting additional interaction
      mechanisms may exist. As indinavir and cyclosporin are substrates for both CYP3A4
      and the multi drug transporter P-glycoprotein we hypothesized that modulation of
      P-glycoprotein expression and function by SJW may contribute to the development
      of potentially harmful drug-drug interactions. METHODS: Healthy volunteers were
      randomized to either SJW (0.15%) 600 mg three times daily for 16 days (n = 15) or
      placebo (n = 7). Blood samples were obtained for P-glycoprotein expression and
      function at baseline, 16 and 32 days post treatment. Peripheral blood lymphocytes
      (PBMCs) were isolated by Ficoll density gradient centrifugation, fixed and
      permeabilized. Cells were stained with a P-glycoprotein specific antibody,
      quantified by flow cytometry and median fluorescence intensity (MFI) values
      obtained. Vimentin and IE (nonsense antibody) were used as controls. The presence
      of the MDR 1 gene product was confirmed by RT-PCR. P-glycoprotein mediated drug
      efflux was determined as a function of rhodamine efflux in the absence and
      presence of ritonavir. Data are expressed as mean +/- s.d. and were subjected to
      nonparametric analysis. RESULTS: P-glycoprotein expression increased 4.2 fold
      from baseline in subjects treated with SJW (7.0 +/- 1.9 vs 29.5 +/- 14.3 (MFI); P
      < 0.05). There was no effect with placebo (5.1 +/- 1.3 vs 6.0 +/- 1.9 MFI). SJW
      increased P-glycoprotein mediated rhodamine efflux (reduced ratio) compared with
      baseline (0.12 +/- 0.04 vs 0.24 +/- 0.18 P < 0.05). There was no change with
      placebo. Ritonavir (5 microm) inhibited P-glycoprotein mediated efflux in both
      groups producing greater intracellular accumulation of rhodamine. However, this
      effect was attenuated following treatment with SJW (23.9 +/- 15.3% vs 75.4 +/-
      16.4% P < 0.05). CONCLUSIONS: SJW increased expression and enhanced the drug
      efflux function of the multi drug transporter P-glycoprotein in PBMCs of healthy
      volunteers. This may represent a second mechanism for the drug-herb interactions
      seen in clinical practice and account for the discrepancies between in vitro and
      in vivo data. Since P-glycoprotein and CYP3A4 have distinct though overlapping
      substrates, patients receiving drugs, which are P-glycoprotein substrates should
      be warned against self-medication with SJW as clinically significant drug
      interactions may occur.

PMID- 11849199
TI  - Randomized cross-over clinical trial to study potential pharmacokinetic
      interactions between cisplatin or carboplatin and etoposide.
AB  - AIMS: Cisplatin and carboplatin are often used in combination with etoposide. In
      a randomized cross-over study, the potential interaction between the two platinum
      drugs and the metabolism of etoposide was explored. In vitro investigations using
      human liver microsomes were also performed. METHODS: Etoposide was administered
      to 15 patients over 3 days, with the platinum drug administered on day 2. The
      alternate platinum drug was administered on the second course. The
      pharmacokinetics of etoposide were determined on all 3 days of each cycle. The
      effect of platinum drugs on etoposide metabolism by human liver enzymes was
      explored in vitro. RESULTS: Neither cisplatin nor carboplatin coadministration
      affected the pharmacokinetics of etoposide during cycle 1. When carboplatin was
      administered on course 2, etoposide AUC was 8% higher on day 2 compared with day
      1 or day 3 (for day 2 vs day 3, 95% CI: -0.72, -0.08 mg ml(-1) min). In contrast,
      cisplatin on course 2 increased the AUC of etoposide (28%) on day 3 (day 3 vs day
      1, 95% CI: 0.67, 2.09 mg ml(-1) min), with no effect on day 2. In vitro
      carboplatin and cisplatin (10-100 microm) inhibited the metabolism of etoposide,
      if rat liver microsomes were preincubated (30 min) with NADPH and the platinum
      complexes. With human liver microsomes a small effect on etoposide metabolism,
      but not on catechol formation, was observed. CONCLUSIONS: The interaction between
      etoposide and platinum drugs is small and, given the pharmacokinetic variability
      seen with etoposide, the clinical impact is unlikely to be significant.

PMID- 11849200
TI  - What benefit do patients expect from adding second and third antihypertensive
      drugs?
AB  - AIMS: To discover whether patients have the same expectations of benefit from
      taking the first and any additional drugs for the treatment of hypertension and
      to investigate any patient characteristics which predict willingness to take
      treatment. METHODS: This was an anonymous questionnaire survey carried out in a
      single primary care group. A random sample of patients from the practice list
      stratified by age and gender were surveyed to determine what benefit they
      required before deciding to receive first and subsequent drugs to treat
      hypertension. They were asked to indicate the largest number needing treatment
      for 5 years (NNT5) to prevent myocardial infarction in 1 (smallest benefit) that
      would persuade them of the need for treatment. Demographic information which
      might explain variability in enthusiasm for treatment was also collected. RESULTS
      PARTICIPANTS: required far higher benefit to consider drug treatment than
      expected with a mean NNT5 for the first treatment of 15.0 (95% CI 12.3, 17.8).
      Marginal benefit demanded for the addition of second and third treatments was at
      least as great with an NNT5 of 13.2 (95% CI 10.8, 15.7) and NNT5 of 11.0 (95% CI
      8.6, 13.4). Additional factors influencing willingness to take treatment were
      gender with a difference in NNT5 between men and women of 7.1 (95% CI 1.7, 12.5),
      difficulty in making the decision (very easy vs very difficult) of 14.9 (95% CI
      6.0, 23.8), and years in full time education 2.0 (95% CI 0.9, 3.0) for each
      additional year of education. Any slope of NNT5 with increasing number of tablets
      disappeared when gender, years in education, and difficulty in reaching a
      decision were taken into account simultaneously. CONCLUSIONS: People may have
      greater expectation of benefit from antihypertensive drug treatment than it
      provides. They certainly do not view the addition of subsequent drugs as any
      lesser step than starting the first in terms of the benefit expected. Full
      understanding of both the risks and benefits may be of critical importance with
      those spending longer in full time education and those expending more effort in
      making the decision accepting more treatment. The discrepancy between benefit
      expected and that available demands further research into methods of determining
      patients' expectations and informing individual patient decisions.

PMID- 11849201
TI  - Statins and the risk of idiopathic venous thromboembolism.
AB  - AIMS: To evaluate the association between current statin use and the risk of
      idiopathic venous thromboembolism (VTE). METHODS: A population-based
      retrospective follow-up with a nested case-control analysis using the General
      Practice Research Database. RESULTS: There were 72 cases of idiopathic VTE. Using
      normolipidaemic nonuse as the reference group, the adjusted relative risks for
      idiopathic VTE for current/recent statin use, past statin use, past other lipid
      lowering drug use, and hyperlipidaemic nonuse were 0.8 (0.3, 2.7), 2.4 (0.6,
      10.0), 1.8 (0.4, 7.4), and 0.9 (0.4, 2.0) in the follow-up analysis, and were 1.1
      (0.3, 4.3), 3.7 (0.6, 24.1), 2.0 (0.3, 11.6), and 0.4 (0.2, 1.2) in the case
      control analysis. CONCLUSIONS: Current statin use was not associated with a
      reduced risk of idiopathic VTE.

PMID- 11849203
TI  - Histoplasma capsulatum in peripheral blood smears.

PMID- 11849202
TI  - Comparison of the clinical efficacy of standard and mucoadhesive-based nasal
      decongestants.
AB  - AIMS: To compare two xylometazoline 0.1% preparations: reference commercial
      solution (RS) and test mucoadhesive solution (TS). METHODS: Twenty subjects with
      perennial allergic rhinitis (age range 18-69 years, 5 atopic, 7 men) applied
      randomly in turn TS and RS for 5 days in a double-blind crossover clinical trial.
      Nasal airflow resistance (NAR), nasal symptoms (6 grade scoring), frequency of
      application (times/day), and side-effects were recorded. RESULTS: Mean ratio
      TS/RS of areas under the resistance/time curves for NAR +/- 90% CI: 3.56 +/-
      0.92; mean TS-RS differences +/- 95% CI: for congestion: -1.12 +/- 0.59, for
      frequency of application: -1.10 +/- 0.20. Subjects experienced fewer side-effects
      with TS. CONCLUSIONS: A mucoadhesive solution with a decongestant had a greater
      and longer lasting effect on nasal congestion in subjects with perennial allergic
      rhinitis than the commercially available decongestant solution. It also caused
      fewer side effects.

PMID- 11849204
TI  - A case of compound heterozygosity for Hb S and Hb S Oman.

PMID- 11849205
TI  - Cytoprotective function of keratinocyte growth factor in tumour therapy-induced
      tissue damage.

PMID- 11849206
TI  - Prospects for anti-ras drugs.

PMID- 11849207
TI  - P-glycoprotein, lung resistance-related protein and multidrug resistance
      associated protein in de novo adult acute lymphoblastic leukaemia.
AB  - P-glycoprotein (P-gp), lung resistance-related protein (LRP) and multidrug
      resistance-associated protein (MRP) expression, and blast cell intracellular
      daunorubicin accumulation (IDA) were evaluated in 95 previously untreated cases
      of adult acute lymphoblastic leukaemia (ALL) using flow cytometry. Forty-five out
      of 95 (47%) patients were P-gp positive (+), 12/66 (18%) were LRP+ and 11/66
      (17%) were MRP+. Eighteen out of 66 (28%) patients showed a simultaneous
      multidrug resistance (MDR)-related protein expression higher than controls for
      more than one protein, while 24/66 (36%) cases did not overexpress any protein.
      Twenty-one out of 24 (87%) cases overexpressing at least one MDR-related protein
      had a defect in accumulating daunorubicin into their blast cells, while only 4/24
      (16%) cases who did not overexpress any protein had similar features. The
      complete remission rates were similar in MDR-positive and -negative (-) patients
      but relapses within 6 months were more frequent in P-gp+ cases, and therefore the
      disease-free survival duration was shorter in P-gp+ than in P-gp- patients (P =
      0.01). The number of MRP+ and/or LRP+ cases was too small to be able to draw any
      conclusion on their role in affecting or predicting therapy outcome. In
      conclusion, P-gp overexpression associated with a defect in daunorubicin
      accumulation is a frequent feature in adult ALL at onset and seems to be related
      to poorer therapy outcome and, consequently, a shorter disease-free survival. LRP
      and MRP overexpression seems to be a rare event and no conclusion can be drawn on
      its prognostic role.

PMID- 11849208
TI  - Cytotoxicity of 2-chlorodeoxyadenosine and arabinosylcytosine in leukaemic
      lymphoblasts from paediatric patients: significance of cellular nucleoside
      transporter content.
AB  - 2-chlorodeoxyadenosine (2-CdA) and arabinosylcytosine (araC) are nucleoside drugs
      that are used to treat various leukaemias, although 2-CdA has not been tested
      extensively in children with acute lymphoblastic leukaemia (ALL). Nucleoside
      cytotoxicity depends on the conversion of these agents to 5'-phosphate
      derivatives, following drug entry into cells via nucleoside transport (NT)
      processes. This study compared es nucleoside transporter content, determined
      using a flow cytometric assay with SAENTA [5'-S-(2-aminoethyl)-N6-(4-nitrobenzyl)
      5'-thioadenosine] fluorescein, and cytotoxicities of 2-CdA and araC in fresh
      lymphoblasts from previously untreated paediatric ALL patients and the human T
      lymphoblast cell line, CCRF-CEM. Lymphoblast samples from individual patients
      ranged widely in sensitivity to both 2-CdA (IC50, 6 nmol/l to > 5 micromol/l;
      mean = 418 nmol/l; n = 8) and araC (IC50, 59 nmol/l to > 5 micromol/l; mean =
      1050 nmol/l; n = 7), although IC50 values for the two drugs were correlated (r =
      0.78, P = 0.032, n = 7). Cellular es nucleoside transporter content varied more
      than 35-fold among samples from 10 patients. The correlation between es
      nucleoside transporter content and drug sensitivity was statistically significant
      for araC (r = -0.93, P = 0.023, n = 5), but not for 2-CdA (r = -0.57, P = 0.23, n
      = 6). Exposure of CCRF-CEM cells to araC resulted in a substantial araC
      concentration-dependent increase in the relative survival of es transporter
      deficient cells, whereas the increase was slight following exposure to 2-CdA. We
      conclude that, in ALL lymphoblasts, es nucleoside transporter content is a
      determinant of araC sensitivity and that a deficiency in NT may impart resistance
      to araC.

PMID- 11849210
TI  - Surface immunoglobulin on B lymphocytes as a potential target for specific
      peptide ligands in chronic lymphocytic leukaemia.
AB  - With the aim of producing unique targets for malignant cells we have identified
      peptide ligands for the clonal surface immunoglobulin isolated from the B cells
      of a chronic lymphocytic leukaemia (CLL) patient. The peptides were identified
      from random-peptide phage-display libraries. The obtained ligands bound
      specifically to the surface of the target lymphocytes as well as to clonal
      immunoglobulin in lysate from the same cells. Peptide-based antigen mimotopes may
      have a future use in targeted therapy of CLL and other B-cell-derived
      malignancies displaying surface immunoglobulin.

PMID- 11849209
TI  - Oral cladribine for B-cell chronic lymphocytic leukaemia: report of a phase II
      trial with a 3-d, 3-weekly schedule in untreated and pretreated patients, and a
      long-term follow-up of 126 previously untreated patients.
AB  - A phase II study was undertaken to evaluate the efficacy and toxicity of a new
      schedule of cladribine administration (10 mg/m2 orally daily for 3 d every 3
      weeks) in 107 patients with B-cell chronic lymphocytic leukaemia (CLL). To
      minimize toxicity, treatment withdrawal criteria were defined. The results of the
      63 previously untreated patients were retrospectively compared with 63 from an
      earlier study using a 5-d monthly schedule. The compiled data were analysed for
      prognostic factors for survival. No significant difference regarding response
      were seen in the two cohorts of the 126 previously untreated patients. The
      complete response (CR), nodular partial response (nPR) and partial response (PR)
      rates were 15%, 21% and 41%. Quality of response had no impact on survival. The 3
      and 5-year overall survival for previously untreated patients was 73% and 58%,
      respectively, with a median follow-up of 54 months. Pretreatment haemoglobin
      <11.0 g/dl and elevated beta-2-microglobulin had a negative influence on
      survival. Major infections occurred in 21% of patients in the 3-d study compared
      with 35% in the 5-d study. The overall response (OR) and CR rates in the 40
      previously treated patients were 34% and 5% respectively. Median overall survival
      was 24 months and median progression-free survival for responding patients was 14
      months. Cladribine used as a single agent is an effective treatment with an
      acceptable safety profile for pretreated and untreated B-CLL. The achievement of
      complete remission was not a prerequisite for long-term survival.

PMID- 11849211
TI  - Dual effects of arsenic trioxide (As2O3) on non-acute promyelocytic leukaemia
      myeloid cell lines: induction of apoptosis and inhibition of proliferation.
AB  - Clinical efficacy of As2O3 has been shown in patients with relapsed acute
      promyelocytic leukaemia (APL). There is evidence that the effects of As2O3 are
      not restricted to events specific for APL. As2O3 might target mechanisms involved
      in the pathogenesis of other malignancies. We assessed susceptibility to
      induction of apoptosis by As2O3 and cytostatics in 22 myeloid and non-myeloid
      malignant cell lines. As2O3 was used in concentrations of 0.01-10 micromol/l.
      Cell lines displayed different kinetics of response and different sensitivity to
      As2O3. The minimum concentration of As2O3 for induction of apoptosis was 0.1
      micromol/l. High concentrations of As2O3 (5 micromol/l) induced apoptosis in a
      large proportion of cells in all cell lines tested. Low (1 micromol/l As2O3)
      concentrations induced apoptosis in NB-4, HL-60, U-937, CEM, HL-60, KG-1a, PBL
      985, ML-2 and MV-4-11, but not in HEL, K-562, KG-1 and Jurkat up to 35 d of
      incubation. However, the non-apoptotic population of 1 micromol/l As2O3-treated
      HEL, K-562, K-562 (0.02), K-562(0.1) and Jurkat showed reduced proliferation. CEM
      as well as its' multidrug-resistant derivatives were sensitive to 1 micromol/l
      As2O3. In summary, these data demonstrate that As2O3-induced apoptosis is not
      restricted to cell lines with t(15;17). Apoptosis was induced in vitro by As2O3
      concentrations that are achievable in vivo after infusion of well-tolerated As2O3
      doses. Thus, As2O3 might be a suitable therapeutic agent for malignancies other
      than APL provided the adequate dose and duration of As2O3 treatment are used.

PMID- 11849212
TI  - Increased incidence of mitochondrial cytochrome c-oxidase gene mutations in
      patients with myelodysplastic syndromes.
AB  - Mitochondria (mt) play an important role in both apoptosis and haem synthesis.
      The present study was conducted to determine DNA mutations in mitochondrial
      encoded cytochrome c-oxidase I and II genes. Bone marrow (BM) biopsy and
      aspirate, peripheral blood (PB) and buccal smear samples were collected from 20
      myelodysplastic syndrome (MDS) patients and 10 age-matched controls. Cytochrome c
      oxidase I (CO I) and II (CO II) genes were amplified using polymerase chain
      reaction and sequenced. CO I mutations were found in 13/20 MDS patients and the
      CO II gene in 2/10 normal and 12/20 MDS samples, irrespective of MDS subtype.
      Mutations were substitutional, deletional and insertional. CO I mutations were
      most common at nucleotide positions 7264 (25%) and 7289 (15%), and CO II
      mutations were most common at nucleotide positions 7595 (40%) and 7594 (30%),
      suggesting the presence of potential 'hot-spots'. Mutations were not found in
      buccal smears of MDS patients and were significantly higher in MDS samples
      compared with age-matched controls in all cell fractions (P < 0.05), with bone
      marrow high-density fraction (BMHDF) showing a higher mutation rate than other
      fractions (P < 0.05). MDS marrows showed higher levels of apoptosis than normal
      controls (P < 0.05), and apoptosis in BMHDF was directly related to cytochrome c
      oxidase I gene mutations (P < 0.05). Electron microscopy revealed apoptosis
      affecting all haematopoietic lineages with highly abnormal, iron-laden
      mitochondria. These results suggest a role for mt-DNA mutations in the excessive
      apoptosis and resulting cytopenias of MDS patients.

PMID- 11849213
TI  - Melphalan treatment in patients with myelofibrosis with myeloid metaplasia.
AB  - Between January 1985 and December 1992, 104 consecutive patients with symptomatic
      myelofibrosis with myeloid metaplasia (MMM) [splenic enlargement >5 cm and/or
      transfusional requirement or Hb < 10 g/dl and/or white blood cell (WBC) count >20
      x 10(9)/l and/or platelets >1.0 x 10(9)/l] received low-dose Melphalan (2.5 mg/3
      times/week) to evaluate the efficacy and toxicity of this approach. Among 99
      evaluable patients, 66 (66.7%) achieved a response after a median time of 6.7
      months: 26 (26.3%) had a normalization of all clinical and haematological
      parameters (complete response, CR) and 40 (40.4%) showed an improvement >50%
      (partial response, PR). Thirty-three patients (33.3%) were resistant. Reversible
      haematological toxicity was the most common complication. Median durations of CR
      and PR were 28.4 and 26 months respectively: median survival of CR + PR patients
      was 71.2 months (95%CI: 33.8-108.7) versus 36.5 months (95%CI: 24.5-48.5) for the
      non-responders (log-rank test, P =0.002). In the multivariate analysis, the
      following variables were significantly associated with a shorter survival:
      anaemia [hazard risk (HR) = 2.7], WBC count >20 x 10(9)/l (HR = 2.4) and not
      achieving any type of response, either partial or complete (HR = 3.9). In
      conclusion, Melphalan could be a promising first-line option for MMM patients
      with clinical or haematological symptoms requiring treatment.

PMID- 11849214
TI  - Hypermethylation of the P15INK4b and P16INK4a in agnogenic myeloid metaplasia
      (AMM) and AMM in leukaemic transformation.
AB  - Hypermethylation of p15 and p16 genes was determined in 32 patients with
      agnogenic myeloid metaplasia(AMM), also known as idiopathic myelofibrosis (MF).
      These included 10 patients in leukaemic transformation phase. Using polymerase
      chain reaction-based methylation analysis assay methods, with substantiation
      using Southern blot analysis, the study showed no hypermethylation of p15 or p16
      genes in the chronic phase of AMM, but p15 gene hypermethylation was found in
      four patients (40%) and p16 gene hypermethylation in two patients (20%) when they
      were in leukaemic transformation stage. Furthermore, two of the patients in
      leukaemic transformation were found to have both p15 and p16 gene
      hypermethylation, demonstrating possible multiple gene hypermethylation in the
      same patient. Thus, hypomethylation agents for treating patients with AMM in
      leukaemic transformation may be appropriate for future trials.

PMID- 11849215
TI  - Genetic polymorphisms in microsomal epoxide hydrolase and susceptibility to adult
      acute myeloid leukaemia with defined cytogenetic abnormalities.
AB  - Acute myeloid leukaemia (AML) cases with different chromosomal abnormalities may
      reflect different aetiologies. Benzene exposure, from a number of sources
      including smoking, is one risk factor for AML. Individual susceptibility to
      benzene may depend on differences in expression of metabolizing enzymes. We
      tested the hypothesis that smoking as well as genetic polymorphisms in the
      microsomal epoxide hydrolase gene (HYL1), an enzyme involved in benzene
      metabolism, could be risk factors for AML with defined chromosomal abnormalities.
      Twenty-six AML cases with -7/del(7q) and 24 cases with t(8;21), as well as 43
      cases with normal karyotype and 155 age-, sex- and residence-matched controls,
      were drawn from a large case-control study on adult acute leukaemia. Current
      smoking was significantly associated with the cytogenetic abnormalities t(8;21)
      or -7/del(7q) (OR = 4.9; 95%CI = 2.1-11.5) but not with a normal karyotype,
      relative to individuals who were not current smokers. A putative high activity
      HYL1 phenotype [exon 3, residue 113 (Tyr/Tyr) and exon 4, residue 139 (His/Arg or
      Arg/Arg)] was associated with a significantly increased AML risk in men with 
      7/del(7q) or t(8;21) (OR = 4.4; 95%CI 1.1-17.0) but not with a normal karyotype.
      This suggests that AML cases with defined chromosomal abnormalities could be
      related to specific carcinogen exposures and, furthermore, suggests that smoking
      and genetic polymorphisms in HYL1 could be risk factors for AML with -7/del(7q)
      or t(8;21).

PMID- 11849216
TI  - Severe decrease in peripheral blood dendritic cells in hairy cell leukaemia.
AB  - Clinical studies in hairy cell leukaemia (HCL) have linked the frequent
      occurrence of infections due to intracellular pathogens and a profound
      monocytopenia. More recently, dendritic cells (DC), a subset of which are related
      to monocytes, were shown to be the professional antigen-presenting cells which
      stimulate the adaptive immune response. Using membrane markers and flow
      cytometry, we determined in peripheral blood whether various DC subsets and
      monocytes were impaired in HCL. Lymphoid and myeloid DC were virtually absent in
      five HCL patients with active disease. After treatment, both DC and monocytes
      recovered slowly. The decrease in DC suggests that defective antigen presentation
      could affect susceptibility to intracellular pathogens in HCL.

PMID- 11849217
TI  - Chromosomal abnormalities in T-cell large granular lymphocyte leukaemia: report
      of two cases and review of the literature.
AB  - Cytogenetic information on T-cell large granular lymphocyte leukaemia (T-LGL;
      large granular lymphocytosis) is limited. We report two cases of T-LGL with
      unusual karyotypic aberrations. The first case showed a novel inv(7)(p15q22) as
      the sole chromosomal abnormality, while the second case showed an inv(14)(q11q32)
      with evidence of clonal evolution. The breakpoints 7p14-p15 and 14q11 coincide
      with the T-cell receptor (TCR)-gamma and TCR-alpha/TCR-delta gene loci
      respectively. This is the first report describing the possible involvement of T
      cell receptor genes in karyotypic aberrations in T-LGL.

PMID- 11849218
TI  - Identification of a novel WT1-derived peptide which induces human leucocyte
      antigen-A24-restricted anti-leukaemia cytotoxic T lymphocytes.
AB  - We previously reported the establishment of a Wilms' tumour (WT)1-derived peptide
      (CMTWNQMNL)-specific and human leucocyte antigen (HLA)-A24-restricted anti
      leukaemia cytotoxic T lymphocyte (CTL) line, TAK-1. In this study, we have
      established a novel WT1-derived peptide (RWPSCQKKF)-specific CD8+ CTL line,
      designated NIM-1. NIM-1 lysed HLA-A24-positive leukaemia cells, but not HLA-A24
      negative leukaemia cells or normal cells. The effects of TAK-1 and NIM-1 on
      cytotoxicity against leukaemia cells were not synergistic, suggesting that
      recognition of a single epitope on the tumour-specific antigen by CTLs is
      sufficient to exert maximal cytotoxic activity against tumour cells.

PMID- 11849219
TI  - A novel immunocytochemical assay for the detection of serotonin in platelets.
AB  - A method for the rapid, inexpensive and easy detection of platelet serotonin (5
      hydroxytryptamine, 5-HT) is not currently available. Consequently, many patients
      suffering from unresolved platelet-related bleeding disorders are not examined
      for a possible platelet 5-HT deficiency. The direct measurement of 5-HT
      concentration with high-performance liquid chromatography (HPLC) or serotonin
      enzyme-linked immunosorbent assay (ELISA) is costly and highly demanding.
      Indirect methods, which determine the content of ATP or calcium with lumi
      aggregometry or electron microscopy, rely upon the assumption that the ATP or
      calcium concentration is equivalent to that of 5-HT. We have developed a
      fluorescence-based assay for 5-HT that can be performed within 2 h on fresh or
      frozen samples using a fluorescence microscope or a flow cytometer. The assay
      requires only 0.2 ml of platelet-rich plasma and might therefore be of particular
      interest for paediatric patients. Samples from control and patient donors were
      analysed for 5-HT with the new immunocytochemical assay in comparison with HPLC
      and/or 5-HT ELISA. Patients with Hermansky-Pudlak syndrome were readily
      identified. The new assay was also reliable in cases where the 5-HT content of
      dense granules was not correlated with the calcium or ATP content, such as in
      calcium deficiency or in the presence of selective serotonin reuptake inhibitors.

PMID- 11849220
TI  - Elevation of serum thrombopoietin precedes thrombocytosis in acute infections.
AB  - To clarify the mechanisms underlying thrombocytosis secondary to infections, we
      longitudinally studied serum levels of thrombopoietin (TPO) and interleukin (IL)
      6 in 15 infants and young children with prominent thrombocytosis (platelets >700
      x 10(9)/l) following acute infections and 116 age-matched controls using an
      enzyme-linked immunosorbent assay. The subjects included nine patients with
      bacterial infections, three with viral infections and three with non-determined
      pathogens. TPO values in the controls were 2.24 +/- 0.87 fmol/ml (mean +/- SD)
      with a 95% reference interval of 0.85-4.47 fmol/ml. In the first week of
      infection, platelet counts were normal, but TPO values increased (approximately
      10.73 fmol/ml). TPO levels peaked on day 4 +/- 2 at 6.44 +/- 2.37 fmol/ml and
      then fell gradually. When platelet counts peaked in the second and third weeks,
      TPO levels were similar to the controls. IL-6 levels in the first week rose and
      dropped more rapidly than TPO. Serum TPO values were significantly correlated
      with C-reactive protein levels (r = 0.688, P < 0.001) and IL-6 levels (r = 0.481,
      P = 0.027). These results suggest that TPO contributes to thrombocytosis
      following infections in conjunction with IL-6, arguing for additional regulatory
      mechanisms of blood TPO levels.

PMID- 11849221
TI  - Rapid reversal of oral anticoagulation with warfarin by a prothrombin complex
      concentrate (Beriplex): efficacy and safety in 42 patients.
AB  - Beriplex, a prothrombin complex concentrate (PCC), was administered to 42
      patients requiring immediate reversal of their oral anticoagulant therapy. The
      dose administered was determined using the pretreatment International Normalized
      Ratio (INR). Blood samples were obtained before treatment and at 20, 60 and 120
      min after treatment. The following investigations were performed on all samples -
      INR, clotting factors II, VII, IX and X, coagulation inhibitors protein C (PC)
      and antithrombin (AT), and other markers of disseminated intravascular
      coagulation, plasma fibrinogen, D-dimer and platelet count. Immediate reversal of
      the INR, the vitamin K-dependent clotting factors and PC was achieved in
      virtually all patients. Reduced AT levels were present in 18 patients before
      treatment. Further slight AT reductions occurred in four patients, but other
      associated abnormalities of haemostasis were observed in only one of the four
      patients. One patient with severe peripheral vascular disease, sepsis and renal
      and cardiac failure died of a thrombotic stroke following leg amputation, 48 h
      after receiving Beriplex. No other arterial and no venous thromboembolic events
      occurred within 7 d of treatment. Beriplex is effective in rapidly reversing the
      anticoagulant effects of warfarin, including PC deficiency, without inducing
      coagulation activation. Caution should continue to be exercised in the use of
      these products in patients with disseminated intravascular coagulation, sepsis or
      liver disease.

PMID- 11849222
TI  - The incidence of recurrent venous thromboembolism in carriers of factor V Leiden
      is related to concomitant thrombophilic disorders.
AB  - The duration of anticoagulant treatment after a first episode of venous
      thromboembolism primarily depends on the risk of recurrence. Variability of
      recurrence rates in factor (F) V Leiden carriers may be due to concomitant
      thrombophilic disorders. A retrospective study was performed in 329 FV Leiden
      carriers with a history of venous thromboembolism (262 probands, 67 relatives).
      The annual rate of first recurrence was estimated in relatives. The contribution
      of concomitant thrombophilic disorders to the recurrence rate was evaluated in
      probands and relatives by a nested case--control analysis in 105 matched pairs of
      carriers either with or without recurrence. The overall annual recurrence rate
      was 2.3 per 100 patient-years. The adjusted risk of recurrence for concomitant
      thrombophilic disorders was: 9.1 (1.3-62.8) for the FII mutation; 1.0 (0.2-4.9)
      for homozygosity for FV Leiden; 1.5 (0.2-9.5) for inherited deficiencies of
      protein C or S; 1.8 (0.7-4.9) for FVIII coagulant activity (FVIII:C) levels
      >122%; 5.4 (1.6-18.6) for fasting homocysteine levels >15.2 micromol/l; and 4.4
      (1.0-18.7) for loading homocysteine levels >45.8 micromol/l. Of these disorders,
      only the FII mutation and hyperhomocysteinaemia significantly increased the risk
      of recurrence in FV Leiden carriers. The estimated recurrence rate ranged from
      0.45 per 100 patient--years after a secondary first event in the absence of
      concomitant disorders to 4.8 per 100 patient-years when a spontaneous first event
      was combined with concomitant disorders. Our study provides supportive evidence
      that the incidence of recurrent venous thromboembolism in heterozygous FV Leiden
      carriers depends on the concomitance of other thrombophilic disorders, in
      addition to whether the first thrombotic event occurred spontaneously.

PMID- 11849223
TI  - Recombinant factor VIIa in the management of surgery and acute bleeding episodes
      in children with haemophilia and high responding inhibitors.
AB  - The management of acute and surgical bleeding episodes in children with severe
      factor VIII or IX deficiency who develop high responding inhibitors presents a
      major therapeutic challenge to clinicians. Recombinant factor VIIa (rVIIa) is an
      effective, reliable and safe treatment that can be used to treat acute bleeding
      episodes prior to commencing an immune tolerance programme and to cover surgical
      procedures until the immune tolerance programme is successful. In a significant
      minority of patients, immune tolerance therapy is ineffective and an alternative
      haemostatic agent such as rVIIa is required for life-long treatment. The present
      study evaluated the use of rVIIa in a paediatric setting. Twelve children, aged 1
      16 years, were treated successfully with rVIIa to prevent surgical bleeding in 20
      surgical procedures (19 central venous access device insertion or removal, 1
      dental extraction). Minor postoperative haematomata developed in 2 out of 20
      cases after regular rVIIa therapy had been discontinued and resolved with a short
      course of rVIIa in both cases. Three children had six life- or limb-threatening
      bleeding episodes. All bleeding episodes resolved with regular rVIIa treatment
      although topical fibrin glue was needed in one child with a frenulum tear. One
      patient required two red cell transfusions for symptomatic anaemia resulting from
      two separate bleeding episodes. The rVIIa therapy was well tolerated and there
      was no evidence of treatment-related complications. We conclude that rVIIa is the
      treatment of choice for the management of surgery and acute life- or limb
      threatening bleeding in children with haemophilia and high responding inhibitors.

PMID- 11849224
TI  - Activation of recombinant alphaIIbbeta3 expressed in Chinese hamster ovary cells
      exposes different binding sites for fibrinogen or von Willebrand factor: evidence
      using monoclonal antibodies to alphaIIbbeta3.
AB  - We have investigated the interaction of von Willebrand factor (VWF) and
      fibrinogen (Fg) with recombinant integrin alphaIIbbeta3 expressed in Chinese
      hamster ovary (CHO) cells either in its native conformation or following partial
      reduction by dithiothreitol (DTT). We found that DTT-treated cells aggregated in
      the presence of soluble VWF as well as Fg, whereas non-treated cells did not.
      Furthermore, we demonstrated that DTT was required to specifically induce
      alphaIIbbeta3-dependent cell adhesion to immobilized VWF, while Fg-dependent cell
      adhesion occurred independently of the activation state of alphaIIbbeta3. By
      comparing the effects of two potent platelet alphaIIbbeta3 inhibitors, monoclonal
      antibodies (mAbs) AP2 and 10E5, we highlighted the different blocking properties
      of these mAbs on VWF or Fg binding to activated alphaIIbbeta3. In particular, AP2
      prevented VWF-dependent but not Fg-dependent CHO cell aggregation. Furthermore,
      AP2 inhibited cell adhesion to VWF, but had no effect on adhesion to Fg. In
      contrast to this distinct effect of AP2 towards these two ligands, mAb 10E5
      inhibited activated alphaIIbbeta3-dependent aggregation completely and adhesion
      partially, whether in the presence of Fg or VWF. These data provide evidence that
      interaction of VWF and Fg with DTT-activated alphaIIbbeta3 relies on distinct
      contact sites exposed on the activated receptor that can be selectively blocked
      by monoclonal antibodies.

PMID- 11849225
TI  - Massive pseudotumour resection with recombinant factor VIIa (NovoSeven) cover.
AB  - Surgical resection is the only definitive treatment for haemophilic pseudotumour.
      For patients with high- responding factor (F)VIII inhibitors, the lack of
      reliable by-passing agents in the past has meant that surgery has been avoided in
      favour of conservative measures. The development of recombinant factor VIIa
      (rFVIIa) has revolutionized the management of surgery in these patients. We
      document the first successful report of the surgical resection of a massive
      pseudotumour in a patient with high responding FVIII inhibitors using rFVIIa to
      achieve haemostasis. Serial post-operative measurements indicated that FVII
      coagulation activity (FVII:C) levels were more sensitive to rFVIIa dose changes
      than the prothrombin time.

PMID- 11849226
TI  - The pharmacodynamics of tinzaparin in healthy volunteers.
AB  - We report the pharmacodynamic properties of tinzaparin (175 U/kg antifactor Xa)
      given as a single daily administration for 5 consecutive days to 14 healthy
      volunteers as a known safe, effective treatment of deep vein thrombosis and
      pulmonary embolism. The Cmax for antifactor Xa (0.87 +/- 0.15 U/ml) was
      associated with a 2.4 +/- 0.5-fold prolongation of the activated partial
      thromboplastin time (APTT) and a high antithrombin activity (0.38 +/- 0.1 U/ml).
      The Cmax value of antifactor Xa was 1.5- and twofold lower than those generated
      by similar doses of nadroparin and enoxaparin respectively. The clearance of
      antifactor Xa activity (1.29 +/- 0.2 l/h) was 1.5- and twofold greater than those
      reported for nadroparin and enoxaparin respectively. These results indicated that
      the antithrombotic and prohaemorrhagic effects of a low molecular weight heparin
      were independent from the absolute levels of antifactor Xa activities and from
      the prolongation of the APTT.

PMID- 11849227
TI  - Long-haul flights and deep vein thrombosis: a significant risk only when
      additional factors are also present.
AB  - To address the association between travel and deep vein thrombosis (DVT) we
      examined the risk factors for DVT in 568 consecutive patients with suspected DVT
      attending King's College Hospital in London. No significant link between DVT and
      long-haul travel was demonstrable in this cohort, with an odds ratio of 1.3 (CI
      0.6-2.8). Risk of DVT was only increased in long-haul travellers if one or more
      additional risk factors were present, with an odds ratio of 3.0 (CI 1.1-8.2).
      Such individuals may benefit from prophylactic measures to minimize risk.

PMID- 11849228
TI  - Cellular copper content modulates differentiation and self-renewal in cultures of
      cord blood-derived CD34+ cells.
AB  - Several clinical observations have suggested that copper (Cu) plays a role in
      regulating haematopoietic progenitor cell (HPC) development. To further study
      this role we used an ex vivo system. Cord blood-derived CD34+ cells were cultured
      in liquid medium supplemented with Kit- ligand, FLt3, interleukin 6 (IL-6),
      thrombopoietin and IL-3. Under these conditions, Cu content, measured by atomic
      absorption, was 7 ng/10(7) cells. Modulation of intracellular Cu was achieved by
      supplementing the cultures with the Cu chelator tetraethylenepentamine, which
      reduced cellular Cu (4 ng/10(7) cells), or ceruloplasmin or Cu sulphate that
      elevated cellular Cu (18 and 14 ng/10(7) cells respectively). The results
      indicated that low Cu content delayed differentiation, as measured by the surface
      antigens CD34, CD14 and CD15, colony-forming unit (CFU) frequency and cell
      morphology, while high Cu accelerated differentiation compared with Cu
      unmanipulated cultures. As a result, expansion of total cells, CFU and CD34+
      cells in low Cu was extended (12-16 weeks), and in high Cu was shortened (2-4
      weeks), compared with control cultures (6-8 weeks). These effects required
      modulation of intracellular Cu only during the first 1-3 weeks of the culture;
      the long-term effects persisted thereafter, suggesting that the decision process
      for either self-renewal or differentiation is taken early during the culture.
      This novel method of controlling cell proliferation and differentiation by copper
      and copper chelators might be utilized for ex vivo manipulation of HPC for
      various clinical applications.

PMID- 11849229
TI  - Persistent polyclonal B lymphocytosis: an expansion of cells showing IgVH gene
      mutations and phenotypic features of normal lymphocytes from the CD27+ marginal
      zone B-cell compartment.
AB  - Persistent polyclonal B-cell lymphocytosis (PPBL) is an unusual and benign
      lymphoproliferation characterized by a polyclonal expansion of B lymphocytes,
      whose nature remains undetermined. The phenotypic analysis of three cases
      revealed that these cells were CD27+ IgM(high) CD21(high) CD5(low) and CD23(low),
      a phenotype associated with the normal marginal zone (MZ) B-cell compartment. As
      MZ B cells have initiated immunoglobulin (Ig)V gene somatic mutations, PPBL IgVH
      genes were sequenced. An average of 73% of these sequences were mutated. The mean
      number of mutation per sequence was 6.9, a number similar to those observed in
      the MZ B-cell compartment.

PMID- 11849230
TI  - A novel deletion of the L-ferritin iron-responsive element responsible for severe
      hereditary hyperferritinaemia-cataract syndrome.
AB  - In the last few years, mutations that cause disease through increased efficiency
      of mRNA translation have been discovered. Hereditary hyperferritinaemia-cataract
      syndrome (HHCS) arises from various point mutations or deletions within the iron
      responsive element (IRE) in the 5'-UTR of the L-ferritin mRNA. Each unique
      mutation confers a characteristic degree of hyperferritinaemia and severity of
      cataract in affected individuals. We report a novel six-nucleotide deletion
      identified in an Italian family presenting with elevated serum ferritin and early
      onset bilateral cataract. This deletion involves a sequence with a TCT repetition
      and may have occurred through a mechanism of slippage mispairing. Because of the
      above repetition, the observed mutation can be interpreted as deletion 22-27, 23
      28, 24-29 or 25-30. Structural modelling predicted an IRE stem modification that
      is expected to markedly reduce the binding to iron-regulatory proteins. A double
      gradient denaturing gradient gel electrophoresis (DG-DGGE) method easily detected
      the above deletion.

PMID- 11849231
TI  - G6PD gene mutations in India producing drug-induced haemolytic anaemia.
AB  - We report 17 cases of glucose-6-phosphate dehydrogenase (G6PD) deficiency with
      drug-induced haemolytic anaemia. In most cases the drug involved was an
      antimalarial. However, we also found two cases in which other drugs could have
      been responsible for the haemolysis. The degree of severity of haemolysis
      differed in the individuals and most required multiple transfusions.

PMID- 11849232
TI  - Transfusion-related acute lung injury caused by human leucocyte antigen class II
      antibody.
AB  - Fcgamma receptor (FcgammaR)-mediated destruction of immunoglobulin-coated red
      blood cells (RBCs) is the underlying mechanism of haemolytic disease of the
      newborn. Human leucocyte antigen (HLA) antibodies in vitro are able to block
      monocyte FcgammaRs and prevent phagocytosis. The intention was to demonstrate
      this effect in vivo upon a volunteer. Plasma containing a non-cytotoxic HLA-DR
      alloantibody was infused into the subject. The FcgammaR blockade was achieved and
      persisted for about 2.5 d, but, unexpectedly, a mild transfusion-related acute
      lung injury (TRALI) was also caused. Monocytes disappeared completely from the
      peripheral blood within the first hour after infusion and a mild pulmonary oedema
      was observed within 3-4 h. The subject recovered within 2 d.

PMID- 11849233
TI  - Platelet alphaIIbbeta3 recombinant autoantibodies from the B-cell repertoire of a
      post-transfusion purpura patient.
AB  - The biallelic human platelet alloantigen (HPA) 1 system encodes a leucine to
      proline substitution at position 33 in the beta3 integrin. Homozygous individuals
      can be immunized by the non-self allele-encoded protein following transfusion or
      during pregnancy. In post-transfusion purpura (PTP), a subsequent recall
      alloantibody response against the non-self form of beta3 is paralleled by the
      destruction of autologous platelets, leading to profound thrombocytopenia.
      Although serological evidence suggests platelet autoantibodies are responsible,
      such autoantibodies are poorly defined. We used variable gene phage display to
      isolate alphaIIbbeta3 autoantibodies formed in the acute phase of PTP and
      determined the epitopes recognized. An immunoglobulin G (IgG)-encoded variable
      heavy-chain domain (VH) gene repertoire containing 4.7 x 10(7) single-chain Fv
      fragments was cloned and three alphaIIbbeta3 antibodies were isolated (clones
      2F2, E3 and B12). All three used different VH genes with a low level of somatic
      mutation for genes derived from gamma-encoding mRNA. Two (2F2 and E3) recognized
      an overlapping epitope and their binding was inhibited by sera from patients with
      PTP; all three recognized Ca2+-dependent compound epitopes on alphaIIbbeta3. Our
      results support the theory that a transient loss of tolerance for alphaIIbbeta3
      with autoantibody formation occurs in PTP.

PMID- 11849234
TI  - Clinical value of immunological monitoring of minimal residual disease in acute
      lymphoblastic leukaemia after allogeneic transplantation.
AB  - In this study, we used multiparameter flow cytometry to quantify minimal residual
      disease (MRD) in 165 serial bone marrow samples from 40 patients diagnosed with
      acute lymphoblastic leukaemia (ALL) who underwent allogeneic stem cell
      transplantation (allo-SCT) from siblings (n = 34) or unrelated donors (n = 6).
      Samples were prospectively taken from 24 patients before starting the
      conditioning regimen, at days +30, +60 and +90 and subsequently every 2-3 months.
      Samples from 16 patients in complete remission (CR) after allo-SCT were taken at
      least twice. Six of 24 patients harboured MRD (0.2-10% of mononuclear cells) at
      transplant and 18 were negative. Estimated disease-free survival for the MRD+ and
      MRD- groups at transplant was 33.3% and 73.5% respectively (P = 0.03). During
      follow-up, increasing MRD levels were detected in nine patients, a finding that
      preceded marrow relapse by 1-6 months. Two patients with stable low MRD levels
      remained in CR. When we used flow cytometry to test the effect of donor leucocyte
      infusions (DLI) in six patients, we observed that the only sustained remission
      was achieved when DLI was applied prior to overt relapse. We conclude that MRD by
      flow cytometry can rapidly assess tumoral burden before transplant to predict
      outcome, and can be clinically useful for the timing of DLI for increasing levels
      of leukaemia after transplant.

PMID- 11849235
TI  - The CD19+ B-cell counts at peripheral blood stem cell mobilization determine
      different levels of tumour contamination and autograft purgability in low-grade
      lymphoma.
AB  - The tumour load of peripheral blood stem cell (PBSC) harvests and the outcome of
      ex vivo immunomagnetic B-cell purging was investigated in 19 patients with low
      grade lymphoma. To quantify the tumour load, we combined fluorescence-activated
      cell sorting measurement of CD19+ B-cells and determination of the B-cell light
      chain ratio (LCR) with consensus complementarity-determining region III
      polymerase chain reaction (CDRIII-PCR) and gene scan analysis. The number of
      tumour cells was calculated using B-cell extracts from the PBSCs. Two different
      patterns were distinguished. In eight patients (42%) with CD19+ B cells >1% in
      the apheresis product, a high tumour load was found, characterized by a
      monoclonal LCR, positive PCR in seven out of eight cases, >5 x 10(7) extracted
      lymphoma cells in six out of seven PCR-assessable cases, and the presence of
      residual lymphoma after purging in six of seven cases. In 11 patients (58%) with
      <1% CD19+ B-cells in the product, a low tumour load was indicated by a polyclonal
      LCR, positive PCR in only 4 out of 11 cases, >5 x 10(7) extracted lymphoma cells
      in zero out of four PCR-assessable cases, and the presence of residual lymphoma
      after purging in zero out of four of these cases. The level of residual lymphoma
      following purging largely depended on the level of tumour contamination. CD19+ B
      cells >50/microl in the peripheral blood at mobilization predicted a high tumour
      load in the apheresis product.

PMID- 11849236
TI  - Interleukin 10, produced in abundance by human newborn T cells, may be the
      regulator of increased tolerance associated with cord blood stem cell
      transplantation.
AB  - The use of human umbilical cord blood as an alternative source of stem cells to
      bone marrow for the reconstitution of the immune system is associated with less
      frequent and less severe incidence of graft-versus-host disease (GVHD). This
      study focuses on aspects of cord blood T-cell biology that may contribute to a
      perceived increased tolerance associated with the neonatal immune response. A
      skewing of the T-helper (Th)1/Th2 phenotype of cord blood T cells towards a Th2
      response has frequently been cited as a possible cause. In this study, primary
      and repeated stimulation via the T-cell receptor (TCR) complex induced a Th0-type
      cytokine response, with both adult and cord blood-derived naive T cells producing
      interferon gamma (IFN-gamma), interleukin 4 (IL-4) and IL-5. IL-10 was induced in
      cord blood T-cell cultures during primary stimulation, while adult T cells began
      to secrete IL-10 only after repeated stimulation. The presence of the antigen
      presenting cell (APC)-derived cytokine IL-1beta inhibited IL-10 production by
      cord blood cells. The effects of IL-12 and IL-4 on T-cell cytokine responses were
      also examined. In addition to their differential Th1/Th2 skewing effects on cord
      and adult T cells, both cytokines augmented IL-10 production in both T-cell
      populations. These findings demonstrate that cord blood T cells may secrete large
      amounts of the anti-inflammatory cytokine IL-10 and that the presence of IL-1beta
      or Th1/Th2 skewing cytokines can regulate its production. This data provides
      support for the recognized tolerant nature of the newborn immune response that
      may contribute to the reduced incidence of GVHD associated with cord blood
      transplantation.

PMID- 11849237
TI  - Epstein-Barr virus-specific T-cell cytotoxicity is mediated through the perforin
      pathway in patients with lymphoproliferative disorders after allogeneic bone
      marrow transplantation.
AB  - The in vivo cytotoxic mechanism of Epstein--Barr virus (EBV)-specific cytotoxic
      lymphocytes was examined in a patient who suffered with EBV-associated
      lymphoproliferative disease (LPD) after bone marrow transplantation (BMT). His
      peripheral CD8+ T-cell count was significantly increased and >70% of these cells
      were EBV-specific by fluorescence-activated cell sorter (FACS) analysis for
      interferon-gamma production. Intracellular perforin expression was markedly
      increased in CD8+ T cells by FACS analysis. The lymphocytes from this patient had
      cytotoxic activity against autologous EBV+ lymphoblastoid cell lines which were
      completely inhibited by concanamycin A, an inhibitor of perforin, and a anti
      human leucocyte antigen (HLA)-class I monoclonal antibody. These results suggest
      that the cytotoxicity was mediated by the perforin, in an HLA-class I-restricted
      manner. We performed serial intracellular perforin analyses in another patient
      who also showed endogenous expansion of EBV-specific CD8+ T cells that coincided
      with an increased EBV-DNA load. Perforin expression in the CD8+ and CD4+ T cells
      paralleled the EBV-specific CD8+ T cells and EBV-DNA load, which also suggests
      that perforin mediates EBV-specific cytolysis in vivo and is responsible for
      effective immunosurveillance against EBV reactivation after BMT. Evaluation of
      host immunity against EBV by determining perforin expression in lymphocytes and
      EBV-specific lymphocytes along with quantification of EBV-DNA may be useful for
      predicting the clinical course of patients with EBV-associated LPD after BMT.

PMID- 11849238
TI  - Unrelated donor bone marrow transplantation for children with juvenile
      myelomonocytic leukaemia.
AB  - Children with juvenile myelomonocytic leukaemia (JMML) have a poor outcome, with
      survival in a minority of patients. The major limitation on success of sibling
      donor bone marrow transplantation for JMML has been reported to be relapse. A
      total of 46 children with a diagnosis of JMML underwent unrelated donor marrow
      (URD) transplantation facilitated by the National Marrow Donor Program. Forty
      three of 46 patients had neutrophil engraftment at a median of 20 d post
      transplant, with platelet recovery in 28 of 40 evaluable patients at a median of
      34.5 d. Thirty-two of 44 evaluable patients developed acute graft-versus-host
      disease (GVHD) (Grades 2-4) and chronic GVHD developed in 14 of 35 evaluable
      patients. At a median follow-up of 2.0 years, probabilities of survival and
      disease-free survival were 42% and 24% respectively. The probability of relapse
      was 58% at 2 years and represents the major cause of treatment failure.
      Multivariate analysis revealed that chronic GVHD was associated with reduced
      relapse [risk ratio 0.20 (95% CI 0.04-1.02, P=0.05)] improved survival [risk
      ratio 0.13 (95% CI 0.03-0.68, P=0.02)] and event-free survival [risk ratio 0.23
      (95% CI 0.06-0.94, P=0.04)]. This study demonstrates that relapse is the major
      cause of treatment failure in patients with JMML undergoing URD transplantation.
      With lower relapse observed in patients with chronic GVHD, new treatment
      strategies that focus on enhancing the graft-versus-leukaemia effect may improve
      survival.

PMID- 11849240
TI  - The genetics of male undermasculinization.
AB  - A review of the genetics of male undermasculinization must encompass a
      description of the embryology of the genital system. The dimorphism of sex
      development consequent upon the formation of a testis and the subsequent
      secretion of hormones to impose a male phenotype is highlighted. Thus, an
      understanding of the causes of male undermasculinization (manifest as XY sex
      reversal, complete and partial) includes reviewing the genetic factors which
      control testis determination and the production and action of testicular
      hormones. The study of disorders of male sex development has contributed
      substantially to knowledge of normal male development before birth. This
      knowledge has been complimented in recent years by the use of targeted murine
      gene disruption experiments to study the sex phenotype, although murine and human
      phenotypes are not always concordant. The investigation of disorders associated
      with male undermasculinization of prenatal onset is described briefly to complete
      the review.

PMID- 11849241
TI  - Transsphenoidal surgery for Cushing's disease: defining cure and following
      outcome.

PMID- 11849242
TI  - Amiodarone-induced thyrotoxicosis: a difficult diagnostic and therapeutic
      challenge.

PMID- 11849243
TI  - Undetectable postoperative cortisol does not always predict long-term remission
      in Cushing's disease: a single centre audit.
AB  - OBJECTIVE: An undetectable postoperative serum cortisol has been regarded as a
      definition of cure in Cushing's disease. However, we noted disease recurrence
      amongst patients with Cushing's disease despite undetectable postoperative
      cortisol levels, and this led us to audit our data. We have also previously
      assessed surgical outcome for acromegaly and microprolactinoma for a single
      surgeon. The aims of this study were two-fold: (i) to investigate the treatment
      and surgical outcome of patients with Cushing's disease. In particular, we wished
      to compare the data with outcome for other pituitary tumours in our centre; and
      (ii) to determine whether undetectable cortisol following surgery is predictive
      of long-term cure for Cushing's disease. PATIENTS AND METHODS: We performed a
      retrospective audit of 97 patients; mean age 39.1 (range: 14-82) years, 78/97
      (80.4%) female, mean follow-up 92 months (range: 6 months to 29 years), with
      Cushing's disease seen in our unit between 1969 and 1998. We documented
      diagnostic investigation, immediate surgical outcome and disease recurrence in
      these patients. RESULTS: All patients had elevated urinary free cortisol (mean
      1270.6 nmol/l, range: 327-3245 nmol/l). In total, 95.5% of patients did not
      suppress with low-dose dexamethasone suppression testing. Hypokalaemia (K < 3.2
      mmol/l) was present in 15.6% of patients; 17.5% of patients did not show cortisol
      suppression with high-dose dexamethasone and 15.8% of patients did not show an
      ACTH rise of > 50% following corticotrophic releasing hormone (CRH)
      administration. There was no significant (> 3) gradient in ACTH or cortisol
      following CRH during inferior petrosal sinus sampling in 27.3% of patients who
      had the test. A pituitary tumour was demonstrated on imaging in 55.8% of
      patients; 10.3% were macroadenomas. Mortality rate following trans-sphenoidal
      surgery was 1%. Following surgery, the immediate postoperative remission rate
      (undetectable postoperative cortisol) was 68.5%. However, 11.5% of these patients
      developed disease recurrence during a mean follow-up period of 36.3 months.
      Considering microadenomas, Cushing's disease patients had an immediate
      postoperative remission rate of 63.2% which is significantly lower (P < 0.05)
      compared to a remission rate of 91.1% in acromegaly. Additionally, new
      postoperative gonadotrophin deficiency (13.9%) and TSH deficiency (25.8%) was
      higher in patients with Cushing's disease compared to patients with acromegaly or
      microprolactinoma. Immediate postoperative remission rates improved from 50% in
      the first decade of a surgeon's career to consistently above 60% in the second
      and third decades, demonstrating a trend which may be attributed to surgical
      experience. CONCLUSIONS: (i) Despite strict criteria for immediate postoperative
      remission and recurrence, undetectable postoperative cortisol is not always
      predictive of long-term remission. (ii) Despite an aggressive surgical approach,
      immediate postoperative remission rates for Cushing's disease are lower compared
      to other microadenomas. The development of new pituitary hormonal deficiency
      following surgery is also commoner than that seen amongst other microadenomas.
      These data have important implications for the follow-up of patients with
      Cushing's disease.

PMID- 11849244
TI  - Clinical experience of amiodarone-induced thyrotoxicosis over a 3-year period:
      role of colour-flow Doppler sonography.
AB  - OBJECTIVE: Current thinking is that amiodarone-induced thyrotoxicosis (AIT) might
      be either iodine-induced thyrotoxicosis in latent hyperthyroidism (Type 1) or
      destructive thyroiditis (Type 2), and also that colour-flow Doppler sonography
      (CFDS) of the thyroid and serum interleukin 6 (IL-6) are tools that can classify
      AIT and direct treatment. To assess the validity of this thinking, our objective
      was to determine whether CFDS and IL-6 identified AIT subgroups with distinct
      features. DESIGN: Retrospective case-note audit of all patients presenting with
      AIT to the Endocrine Department of a UK teaching hospital over a 3-year period.
      To assess proportions of Type 1 vs. Type 2 AIT and to compare and contrast their
      clinical features. PATIENTS: 37 patients were identified with AIT (mean age 65,
      range 20-86 years). In 30 patients in whom AIT persisted, 25 underwent CFDS.
      RESULTS: In 25 patients who underwent CFDS, 10 (40%) were classified as Type 1,
      10 (40%) as Type 2 and 5 (20%) as indeterminate type. In the patients classified
      by CFDS in whom AIT persisted, 40% of Type 1 patients were male vs. 90% of Type 2
      patients. Also, free T4 tended to be lower in patients presenting with Type 1 AIT
      (52.1 +/- 7.5 pmol/l) compared to Type 2 (74.8 +/- 8.1 pmol/l, P = 0.08), free T3
      was lower (8.8 +/- 0.9 vs. 15.6 +/- 3.0 pmol/l, P = 0.03) and the cumulative
      amiodarone dose was lower (66 +/- 20 vs. 186 +/- 28 g, P = 0.002). We used less
      prednisolone to achieve euthyroidism in patients with Type 1 AIT whereas
      carbimazole doses were not different and the time to euthyroidism was the same in
      both groups (81 +/- 21 vs. 88 +/- 13 days). IL-6 was raised in two patients with
      Type 1 and in one patient with Type 2 AIT. CONCLUSIONS: CFDS could characterize
      two distinct subtypes in patients with AIT. Conversely, IL-6 seemed to be an
      unhelpful test in this context.

PMID- 11849245
TI  - Electrophysiological abnormalities of the atrial muscle in patients with
      paroxysmal atrial fibrillation associated with hyperthyroidism.
AB  - OBJECTIVE: Atrial fibrillation (AF) is common in patients with hyperthyroidism.
      Although the choice of an antiarrhythmic agent should be based on its
      electrophysiological effects and the electrophysiological properties of the
      arrhythmia in question, the atrial electrophysiological features of AF associated
      with hyperthyroidism are unknown. The purposes of this study are to clarify the
      atrial electrophysiological abnormalities of AF with hyperthyroidism, and to
      propose effective therapies for AF in patients with hyperthyroidism. SUBJECTS AND
      DESIGN: This study included 117 patients who underwent electrophysiological study
      and were evaluated for thyroid function: 29 patients without AF or
      hyperthyroidism (Group I), 78 patients with lone paroxysmal AF (Group II), and 10
      patients with paroxysmal AF and hyperthyroidism (Group III). The following
      electrophysiological parameters were assessed and measured quantitatively: (1)
      the incidence of abnormal right atrial electrograms during sinus rhythm,
      indicating areas of altered anatomy and conduction where AF is likely to develop;
      (2) the atrial effective refractory period (ERP); and (3) the atrial conduction
      delay (CD), which is induced by early atrial premature beats close to the atrial
      ERP and is thought to facilitate the occurrence of AF. RESULTS: The incidence of
      abnormal right atrial electrograms during sinus rhythm was significantly higher
      in Group II (67.1%) than in Group I (20.0%, P < 0.001) and Group III (22.2%, P =
      0.009). The atrial ERP was significantly shorter in Group III (187 +/- 7 ms) than
      in Group I (215 +/- 36 ms, P = 0.019) and Group II (208 +/- 28 ms, P = 0.022).
      The atrial CD was observed in Group III as well as in Group II. CONCLUSIONS: Our
      data indicate that the electrophysiological features of paroxysmal AF associated
      with hyperthyroidism are essentially different from those of lone paroxysmal AF.
      In patients with paroxysmal AF and hyperthyroidism, a shortening of the
      refractory period in association with a facilitation of the atrial CD could be
      expected to increase the propensity for AF, and a pre-existent arrhythmogenic
      substrate might not be essential to the genesis of AF. These findings suggest
      that the agents that prolong the atrial ERP are effective against AF in patients
      with hyperthyroidism.

PMID- 11849247
TI  - Multigenerational familial medullary thyroid cancer (FMTC): evidence for FMTC
      phenocopies and association with papillary thyroid cancer.
AB  - BACKGROUND: Occurrence in a familial setting is well established for medullary
      thyroid carcinoma (MTC) and has been more recently reported for papillary thyroid
      cancer (PTC). Germline mutations or rearrangements of the RET proto-oncogene are
      the genetic background of the majority of hereditary MTCs and of about 25-40% of
      PTCs. PATIENTS: A large multigenerational familial medullary thyroid cancer
      (FMTC) family, comprised of four generations and a total of 60 subjects, has been
      fully evaluated. Studies on germline RET mutations and polymorphisms, on somatic
      RET activation and on haplotyping with RET-linked markers, were performed.
      RESULTS: RET mutational analysis revealed a rare missense point mutation in exon
      15 of RET (A891S), associated with FMTC. Haplotype analysis showed a co
      segregation between the allelic variant 5 of D10S578 marker (which is tightly
      linked to the RET locus) and the RET mutation. Two patients, from different
      branches of the family, did not harbour the point mutation A891S despite
      histological confirmation of MTC. In these cases, haplotype analysis excluded the
      involvement of the RET gene itself in the pathogenesis of the MTC. In three
      patients, the coexistence, in different foci, of medullary and papillary thyroid
      cancer was documented. The genetic studies did not show ret/PTC rearrangements.
      The microsatellite analysis excluded co-segregation of RET locus with the MTC/PTC
      phenotype. CONCLUSIONS: We report a full clinical and molecular analysis of a
      large FMTC kindred with an uncommon RET mutation. In two family members,
      phenotype and genotype were not concordant, representing the first evidence of
      FMTC phenocopies. Furthermore, the association of familial forms of medullary and
      papillary thyroid cancers has been found in 30% of patients undergoing
      thyroidectomy for MTC. In these situations, genetic analyses excluded the
      possible germline involvement of RET. Though FMTC phenocopies are likely to
      represent an exceptional finding, such a possibility should be taken into account
      in the genetic counselling for MEN 2 syndromes.

PMID- 11849246
TI  - Autoimmune thyroid disease susceptibility loci in a large Chinese family.
AB  - OBJECTIVES: The autoimmune thyroid diseases (AITDs) comprising Graves' disease
      (GD) and Hashimoto's thyroiditis (HT) are complex genetic diseases, which result
      from an interaction between predisposing genes and environmental triggers. The
      aim of our study was to dissect the genetic predisposition to GD and HT in one
      large Chinese family with multiple members affected with AITD. PATIENTS: We
      completed a whole genome screen of a large multiplex Chinese-American family. We
      enrolled 27 family members from three generations. Eight members were affected
      with AITD, six had GD and two had HT. DESIGN: We determined the information
      limits of the family. Power calculations indicated that the maximum attainable
      LOD scores were 5.1 assuming dominant inheritance, and 3.4 assuming recessive
      inheritance. These estimates both assumed 100% penetrance and one gene. Whole
      genome screening was performed using 400 highly polymorphic and densely spaced
      microsatellite markers spanning the entire human genome (intermarker distance <
      10 cM). Linkage analysis was performed using two-point and multipoint parametric
      and nonparametric methods. RESULTS: Initial whole genome screening performed with
      400 microsatellite markers identified two markers that showed evidence for
      linkage to AITD in this family, D11S4191 and D9S175, with two-point LOD scores of
      2.31 and 2.05, respectively. Multipoint linkage analysis focusing on the regions
      containing these markers revealed a maximum multipoint LOD score (MLS) of 2.13
      and a nonparametric linkage score (NPL) of 6.1 for D11S4191 and an MLS of 2.01
      and NPL of 7.5 for D9S175. CONCLUSIONS: These results showed that this Chinese
      family harboured susceptibility loci for AITD which were distinct from those
      previously found in the Caucasian population. This suggests that different
      susceptibility loci exist between different ethnic groups. Furthermore, even
      within a single family from a genetically homogenous population, more than one
      gene was involved in the genetic susceptibility to AITD, supporting the notion
      that AITDs are caused by multiple genes of varying influences.

PMID- 11849249
TI  - Men with acromegaly need higher doses of octreotide than women.
AB  - OBJECTIVE: To investigate the effect of gender on the response of GH to short
      acting octreotide in patients with acromegaly, and on the GH and IGF-1 levels
      during long-term treatment with a slow-release formulation of octreotide. STUDY
      DESIGN AND PATIENTS: Twenty-one men (mean age 54 years; range 26-78) and 15 women
      (mean age 54 years; range 22-74) with acromegaly were treated with subcutaneous
      injections of 100 microg short-acting octreotide twice daily. Serum samples for
      GH were taken before start of treatment, in the morning prior to the injection,
      and 1, 3, 5 and 7 h after the injection. Thirteen men (mean age 56 years; range
      34-78) and 12 women (mean age 64 years; range 28-81) with acromegaly were
      switched from ongoing treatment with short-acting octreotide to injections of the
      slow-release formulation. A 4-h GH-profile and morning IGF-1 were taken at start
      and after 3, 9, 15 and 21 months of treatment. RESULTS: Subcutaneous injections
      of 100 microg octreotide reduced the mean level of GH during a 7-h period to a
      similar extent in men and women compared to the GH levels prior to the
      injections. During long-term treatment with similar doses of the depot
      formulation of octreotide, the mean IGF-1 level remained significantly higher in
      the men than in the women, whereas there were no differences in the mean GH
      levels between the two groups. CONCLUSIONS: The responses to short- and long
      acting octreotide illustrate an effect of gender, due to different sensitivity to
      GH in the periphery. Furthermore, the results show that in the treatment of
      acromegaly, men will need higher doses of octreotide than women to normalize IGF
      1.

PMID- 11849248
TI  - Long-term effects of lanreotide SR and octreotide LAR on tumour shrinkage and GH
      hypersecretion in patients with previously untreated acromegaly.
AB  - BACKGROUND AND OBJECTIVE: The therapeutic efficacy of lanreotide SR and
      octreotide LAR has been studied widely in patients treated previously with
      neurosurgery and/or radiotherapy. These therapies limit the evaluation of the
      long-term effects of somatostatin analogues on tumour shrinkage. Neurosurgical
      and radiotherapy treatments cause irreversible anatomical changes in pituitary
      morphology, which can make accurate evaluation of tumour shrinkage difficult. The
      aim of this study was to investigate the therapeutic efficacy of lanreotide SR
      and octreotide LAR in previously untreated patients with acromegaly. We aimed to
      investigate the long-term effects of these drugs on tumour shrinkage and growth
      hormone (GH) hypersecretion without the confounding influences of previous
      therapy. PATIENTS AND METHODS: Twenty-three newly diagnosed patients with
      acromegaly (14 women, nine men) with active disease began the study; of these,
      three were lost for follow-up, leaving a total of 20 patients to complete the
      study. Patients were assigned randomly to lanreotide SR (12 patients) and
      octreotide LAR (eight patients), and the randomization stratified patients to
      assure a balance between the groups with respect to baseline tumour dimension,
      age and sex. Tumour volume was evaluated by magnetic resonance imaging of the
      sella, and calculated with the rotating ellipsoid formula. A morphological and
      biochemical evaluation was performed at baseline, 12 and 24 months after
      beginning lanreotide SR and octreotide LAR treatment. A reduction of tumour
      volume of at least 10% was considered significant. RESULTS: Biochemical control
      increased progressively throughout the study in patients with microadenomas more
      than in patients with macroadenomas (70% vs. 10%; P < 0.05) and without a
      difference between lanreotide SR and octreotide LAR (41.0% vs. 37.5%; P not
      significant). After 12 months of treatment, mean tumour shrinkage was 28.3 +/-
      18.0%. A greater reduction was observed in macro- vs. microadenomas (40.5 +/-
      17.0% vs. 16.1 +/- 8.0%, respectively; P < 0.05). No statistical difference in
      the tumour shrinking effects of lanreotide SR vs. octreotide LAR was observed
      (26.5 +/- 17.3% vs. 31.1 +/- 16.1%, respectively). At the 24th month of therapy,
      no further overall shrinkage was observed, compared to the 12-month evaluation
      (31.9 +/- 17.2% vs. 28.3 +/- 18.0%) at which there was no difference between
      lanreotide SR and octreotide LAR (30.0 +/- 17.2% vs. 34.8 +/- 16.5%,
      respectively). CONCLUSIONS: This study showed that the new long-acting
      somatostatin analogues, lanreotide SR and octreotide LAR, cause significant
      shrinkage of pituitary GH-secreting adenomas in previously untreated patients
      with acromegaly. This effect was more marked in macroadenomas than microadenomas,
      and did not correlate with control of GH hypersecretion.

PMID- 11849250
TI  - Pulsatile, nyctohemeral and entropic characteristics of GH secretion in adult GH
      deficient patients: selectively decreased pulsatile release and increased
      secretory disorderliness with preservation of diurnal timing and gender
      distinctions.
AB  - INTRODUCTION: The present clinical investigation uses a high-precision GH
      immunofluorometric assay to examine the postulate that principally the amplitude
      mode of GH secretory control is disrupted in adults with GH deficiency. PATIENTS
      AND METHODS: To this end, we investigated GH secretory dynamics in a cohort of 19
      adult GH-deficient (GHD) patients and 19 age-, gender- and body mass index
      matched controls. GHD was established by blunted (< 7 mU/l) GH release during
      insulin-induced hypoglycaemia. Twenty-four-hour serum GH concentration profiles
      obtained by 10-min sampling were analysed by deconvolution, cosinor analysis and
      approximate entropy to appraise pulsatile, diurnally rhythmic, and pattern
      dependent GH secretion, respectively. RESULTS: Deconvolution analysis revealed
      that pulsatile GH release was decreased by threefold, due to amplitude-specific
      damping, detectable GH secretory burst frequency was paradoxically increased by
      twofold, but basal non-pulsatile GH release was fully preserved. GH half-life in
      patients and controls was similar, thus excluding major kinetic differences. The
      acrophase (time of maximum) of the 24-h GH rhythm was unchanged. The regularity
      of the GH release process, as measured by ApEn, was decreased profoundly in GHD
      patients (P < 10(-8)). The changes in GH secretion were similar in irradiated and
      nonirradiated patients. Daily GH secretion was also comparable in male and female
      GHD patients, but plasma IGF-I concentrations were higher in male than female
      patients (P = 0.031). Furthermore, the gender-specific GH ApEn difference,
      evident in controls, was still demonstrable in patients (P = 0.017). The ratio of
      plasma IGF-I and pulsatile GH production was increased threefold in patients (P =
      0.004), pointing to increased sensitivity to GH in GH deficiency and/or non-GH
      dependent IGF-I production. CONCLUSIONS: The present detailed analyses of daily
      GH secretory dynamics in patients with (moderate) GH deficiency document an
      amplitude-specific decrease in pulsatile GH secretion, which is partly
      compensated for by increased GH pulse frequency. The remarkably disorderly
      patterns of GH secretion in patients identify other major alterations in GH
      neuroregulation in such individuals, reflecting withdrawal of expected GH and/or
      IGF-I repression of pulsatile GH secretion. Preservation of the nyctohemeral
      timing of GH release and the gender contrast in GH ApEn in GHD patients would
      also be consistent with partial retention of central neuroregulation and GH/IGF-I
      feedback-dependent control in hypopituitary subjects.

PMID- 11849251
TI  - Physical activity or food intake prior to testing did not affect the
      reproducibility of GH secretion elicited by GH releasing hormone plus GH
      releasing hexapeptide in normal adult subjects.
AB  - OBJECTIVE: Growth hormone deficiency (GHD) in adults is a defined syndrome of
      which the adverse effects on different areas of body function are reversed under
      replacement therapy with GH. The diagnosis of GHD is controversial in adults,
      relying on the GH secretion elicited by the so-called provocative tests of GH
      reserve. Most of the tests in use, including the widely employed insulin
      tolerance test, have been shown to be blunted after daily activities, such as
      mild exercise, heat or food intake, which makes stringent testing conditions
      mandatory in order to assure reproducibility. The combined administration of GH
      releasing hormone (GHRH) and GH-releasing hexapeptide (GHRP-6) is a very
      effective test for the diagnosis of GH deficiency in adults. In the present
      study, the perturbatory action of mild physical activity and food intake on the
      reproducibility of this combined test was assessed. METHODS: Seventeen healthy
      volunteers of both sexes were tested twice on separate occasions with the
      sequential administration of GHRH (90 microg i.v.) plus GHRP-6 (90 microg i.v.)
      as bolus. Eleven subjects underwent the first combined test in the morning under
      basal conditions and the second test was performed in the afternoon of the same
      day after a morning of habitual working activity and after a standard lunch.
      Another group of six subjects underwent similar double testing in the morning and
      in the afternoon after morning activity followed by lunch; however, both tests
      were separated by a period of 6 months. MEASUREMENTS: GH levels were analysed by
      time-resolved fluoroimmunoassay, with sampling every 15 minutes. RESULTS: The
      reproducibility of the GHRH + GHRP-6 test performed on the same day was high,
      with the mean GH peak being 65.4 +/- 8.0 microg/l in the basal state and 51.2 +/-
      9.6 microg/l after lunch, while the area under the curve (AUC) was 2287 +/- 288
      microg/l per 45 minutes in the morning and 1759 +/- 350 after lunch. When a
      period of 6 months had elapsed between the first and the second test, the
      reproducibility was well maintained with a mean GH peak of 42.7 +/- 6.2 microg/l
      in the basal state and 34.3 +/- 3.6 microg/l in the after lunch test, with the
      AUC 1463 +/- 209 and 1164 +/- 106 microg/l per 45 minutes in the morning and
      after lunch, respectively. When analysed individually, physical activity, lunch
      or time elapsed between the two tests did not significantly change the GH peak in
      the subjects tested. CONCLUSIONS: The GHRH + GHRP-6 test of GH reserve is a
      highly reproducible test in adult subjects over time, and is not perturbed by
      common daily activities, such as mild physical exercise or food intake.
      Considering that stringent testing conditions are not required and the whole test
      may be performed in 30 minutes, it may be useful in the clinical setting for the
      diagnosis of GH deficiency in adults.

PMID- 11849252
TI  - Metastatic tumours of the adrenal glands: a 30-year experience in a teaching
      hospital.
AB  - OBJECTIVE: Adrenal metastases are frequently encountered during autopsy but
      uncommonly present clinically. The aim of this study was to evaluate the clinical
      and pathological impact of adrenal metastases in a large series of patients.
      PATIENTS: Four hundred and sixty-four patients (288 men, 176 women) with
      metastatic disease in the adrenal glands over a 30-year period were included in
      the study. MEASUREMENTS: The clinical records and pathological features were
      reviewed. RESULTS: The frequencies of adrenal metastases at autopsies,
      adrenalectomies and fine-needle aspiration biopsies were 3.1%, 7.5% and 33%,
      respectively. The lesions were often seen in elderly patients (mean age, 62, SD =
      13 years). Many of the metastatic lesions in the adrenal gland occurred shortly
      after the detection of a primary tumour (mean latent period = 7 months). Four per
      cent of the adrenal lesions (n = 20) were symptomatic. The symptomatic adrenal
      lesions, as compared with asymptomatic ones, were bigger and seen in younger
      patients. Five patients presented with adrenal insufficiency (Addison's disease)
      and one had massive peritoneal haemorrhage because of metastatic carcinoma.
      Ninety per cent (n = 421) of the metastatic adrenal tumours were carcinomas and
      56% of these were adenocarcinoma. Lung was the most common primary tumour site
      (35%), followed by the stomach (14%), the oesophagus (12%) and the liver/bile
      ducts (10%). The adrenal metastases were bilateral in approximately half of the
      patients (49%, n = 229). The mean diameter of the adrenal metastases was 2 cm (SD
      = 1.9 cm). The mean weight of the right adrenal gland harbouring the metastasis
      was 19 g, while that of the left 20 g. The median survival of the 20 patients
      with symptomatic adrenal lesions was 3 months (range, 0-75 months) after the
      detection of adrenal metastases. Patients with surgically removed adrenal
      metastases had slightly better survival rates than those without surgical
      resection. CONCLUSIONS: A variety of tumours may give rise to adrenal metastases.
      They are often asymptomatic and detected as part of multiorgan metastases.
      Symptomatic cases, albeit rare, may occur. Long-term survival may be achieved in
      selected patients in whom an aggressive surgical approach may be adopted.

PMID- 11849253
TI  - Leydig cell hypoplasia: cases with new mutations, new polymorphisms and cases
      without mutations in the luteinizing hormone receptor gene.
AB  - BACKGROUND: Defective male sex differentiation in patients with hypoplasia of
      Leydig cells (LCH) is caused by deficient LH receptor signal transduction. To
      further investigate the variety of LH receptor gene mutations present in LCH
      patients and their influence on the phenotype, we examined 10 nonrelated patients
      with the clinical presentation of LCH. PATIENTS AND METHODS: Ten patients with a
      clinical phenotype of LCH were analysed for mutations in the complete coding
      region of the LH receptor gene. Exons 1-10 and two overlapping fragments of exon
      11 of the LH receptor gene including all intron-exon boundaries were amplified by
      polymerase chain reaction and sequenced. To screen for frequencies of DNA
      changes, mutation analysis was performed on 45-59 healthy persons using
      denaturation high-performance liquid chromatography. RESULTS: Six new DNA
      alterations were identified. Three of them appear to be new polymorphisms. A G to
      C change at the 28th nucleotide of intron 1 on one allele and a heterozygous CGA
      to CAA transition at codon 124 (R124Q) were found. Both findings in these two
      patients are polymorphisms that occur with a frequency of 17% and 1.7%,
      respectively. A silent heterozygous CTA to TTA change at codon 204 was
      identified. In a patient with micropenis, the analysis revealed a homozygous
      missense mutation at codon 625 (I625K). As reported previously, this alteration
      significantly impaired signal transduction and explains the partial phenotype.
      Finally, in one compound heterozygous patient, two different mutations were
      discovered. At the polymorphic site in exon 1, a 27-bp insertion (CTG)2 AAG
      (CTG)5 CAG and a premature stop codon in the transmembrane segment 4 (W491*) were
      found. Both mutations disrupt signal transduction and explain the complete
      phenotype of this patient. In five patients, no DNA alterations could be
      identified. CONCLUSIONS: Three mutations (33 bp insertion in exon 1; W491* and
      I625K) were identified that explain the phenotype in two patients. In addition,
      most of the patients with the clinical phenotype of LCH did not have causative
      mutations, suggesting that changes in other regions of the LH receptor gene, such
      as the large introns or the promoter region, may be responsible for the majority
      of cases. Alternatively, the displayed phenotype may be the result of other
      genetic defects. Our work further underscores the importance of thorough clinical
      analysis of patients before molecular analysis of a particular gene is performed.

PMID- 11849254
TI  - Allelic loss in clinically and screening-detected primary hyperparathyroidism.
AB  - OBJECTIVE: Parathyroid adenomas frequently harbour deletions of genomic DNA at
      chromosome regions 1p, 6q and 11q. In this study we related clinical
      characteristics in 56 patients with primary hyperparathyroidism (pHPT) to loss of
      heterozygosity (LOH) in these chromosome regions. DESIGN: LOH analysis was
      performed on 56 sporadic parathyroid tumours using a total of 18 microsatellite
      markers for chromosome regions 1p, 6q and 11q. LOH was identified, for either
      radioactive or fluorescent labelled markers, as total absence or reduction of >
      or = 50% of the signal intensity of an allele in the tumour DNA vs.
      constitutional DNA. PATIENTS: Twenty-one of the patients were recruited by a
      population-based screening for pHPT and the remaining pHPT patients were gathered
      from routine clinical practice. RESULTS: In total, 27%, 23% and 23% of the
      tumours showed LOH at 1p, 6q and 11q, respectively. LOH at both 1p and 11q was
      more common in the screening-detected pHPT patients compared to those recruited
      from clinical practice (38% vs. 20%; P = 0.02 and 43% vs. 11%; P = 0.001,
      respectively), while allelic loss at 6q was more prevalent in the latter group
      (11% vs. 31%; P = 0.001). No apparent relationships between LOH at 1p, 6q, and
      11q and clinical characteristics, such as glandular weight, serum levels of PTH
      or calcium, were demonstrated. Moreover, additional LOH analysis of chromosome 1p
      suggested a putative parathyroid tumour suppressor gene(s) in the region between
      markers DS214 and D1S503, spanning approximately 6 cM. CONCLUSION: A high
      frequency of LOH at 1p and 11q in tumours of screening-detected pHPT patients is
      intriguing, and may suggest that inactivation of known (the MEN1 gene) and
      putative tumour suppressor genes at these chromosomal regions is associated with
      a more benign disease.

PMID- 11849255
TI  - Study of diurnal fluctuations of plasma methoxyamines in healthy volunteers.
AB  - OBJECTIVE: We studied the diurnal fluctuations of plasma concentrations of
      methoxyamines (metanephrine and normetanephrine) and of their parent amines
      (epinephrine and norepinephrine) in normotensive subjects. DESIGN: Serial blood
      sampling at 09.00 h, 11.00 h, 12.00 h, 14.00 h, 16.00 h, 18.00 h and 20.00 h in
      28 healthy volunteers at rest. Determination of plasma concentrations of free
      catecholamines and total methoxyamines (free and sulpho-conjugates) was carried
      out by high-performance liquid chromatography with electrochemical detection.
      RESULTS: Mean (+/- SD) plasma concentrations of total metanephrine (MN) and
      normetanephrine (NMN) were 4.31 +/- 1.73 nmol/l (range: 0.96-9.3 nmol/l) and 8.13
      +/- 2.54 nmol/l (range: 3.14-17.0 nmol/l), respectively. The NMN/MN ratio ranged
      between 0.8 and 7.8 (mean +/- SD 2.1 +/- 1.0). Mean plasma concentrations of free
      epinephrine and norepinephrine were 0.21 +/- 0.12 nmol/l (range: 0.06-1.39
      nmol/l) and 1.61 +/- 0.62 nmol/l (range: 0.47-4.01 nmol/l), respectively. Despite
      marked intraindividual fluctuations, mean methoxyamine and catecholamine levels
      remained constant over the entire duration of the experiment. CONCLUSIONS: The
      absence of fluctuations of plasma levels of total methoxyamines suggests that
      their measurement could be carried out at any time within the diurnal time frame.
      Further investigations, however, remain necessary to validate these findings in
      patients with hypertension and/or pheochromocytoma, and to explain the ever
      important intraindividual variation in plasma concentrations of methoxyamines and
      of their parent compounds.

PMID- 11849256
TI  - Isolated pituitary granuloma by atypical Mycobacterium in a nonimmunosuppressed
      woman.
AB  - A 32-year-old woman presented with a 10-day history of fever (38.0 degrees C),
      headaches, nausea, vomiting and a 6-month history of diabetes insipidus and
      amenorrhoea. Two months previously she had undergone a surgical drilling of the
      right mastoid area because of mastoiditis. Endocrine investigation showed
      elevated serum prolactin levels, secondary adrenal and gonadal failure and a
      normal thyroid function. Cranial MRI scan revealed a contrast enhancing
      intrasellar mass (approximately 2 cm) of heterogeneous appearance with
      suprasellar extension and thickening of the pituitary stalk. Lumbar puncture was
      suggestive of aseptic meningitis. The Ziehl-Neelsen stain of cerebrospinal fluid
      (CSF) and the tuberculin skin test were both negative. The pituitary mass was
      removed with a transsphenoidal approach. Histological examination demonstrated
      destruction of the adenohypophysis by epithelioid granulomas with partial caseous
      necrosis and microabscess formation, suggestive of a mycobacterial infection. A
      polymerase chain reaction analysis performed on paraffin-embedded tissue was
      positive for mycobacterial DNA. According to the individual 16S sequence, it was
      identified as Mycobacterium malmoense, an atypical nontuberculous mycobacterium
      (NTM). In conclusion, this is the first case of an isolated pituitary granuloma
      caused by an NTM infection in a nonimmunosuppressed patient.

PMID- 11849258
TI  - The significance of articles appearing in dermatologic surgery.

PMID- 11849261
TI  - Regional anesthesia of the face.

PMID- 11849260
TI  - The tumescent facial block: tumescent local anesthesia and nerve block anesthesia
      for full-face laser resurfacing.

PMID- 11849262
TI  - Pediatric anesthesia in dermatologic surgery: when hand-holding is not enough.
AB  - BACKGROUND: Dermatologic procedures in children may require the use of topical
      and local anesthetics, sedatives, and general anesthesia. OBJECTIVE: To review
      developments in topical and local anesthetics, sedatives, and general anesthesia
      relevant to dermatologic procedures in children. METHODS: Review of the medical
      literature. RESULTS: Topical anesthetics, including EMLA and liposome
      encapsulated lidocaine cream, amethocaine, cetacaine, and benzocaine products may
      be useful for decreasing the pain of cutaneous procedures including intra
      lesional lidocaine infiltration. A variety of sedative and hypnotic agents may be
      utilized for pediatric dermatology procedures, and guidelines for their
      appropriate use have been published. General anesthesia for dermatologic
      procedures in the pediatric population is appropriate for a variety of procedures
      including laser treatment of capillary malformations. CONCLUSION: A variety of
      anesthetic, analgesic, and sedatives may be useful for pediatric cutaneous
      surgery.

PMID- 11849263
TI  - Topical anesthetics update: EMLA and beyond.
AB  - BACKGROUND: Topical anesthetics remain a powerful, new advance for pain relief
      prior to cutaneous procedures. They are frequently used by dermatologists to
      decrease the pain associated with laser pulses, surgical procedures, or soft
      tissue augmentation. EMLA is the most commonly used agent, however, several new
      topical anesthetic agents have been released recently that claim increased
      efficacy and a faster onset of action. OBJECTIVE: We review and compare the
      efficacy of several commonly used topical anesthetics and provide a look into the
      future. CONCLUSION: EMLA remains the most widely used topical anesthetic given
      its proven efficacy and safety by several clinical trials. There has been a
      recent release of several new topical anesthetic agents with some demonstrating
      efficacy after a 30-minute application time. A reservoir of anesthetic is located
      and stored in the upper skin layers during application, providing additional
      anesthetic benefit 30 minutes after removal. As the options for the practitioner
      continue to grow, the demand for faster onset, comparative efficacy, and safety
      trials will continue to be of paramount importance.

PMID- 11849264
TI  - Iontophoresis as a tool for anesthesia in dermatologic surgery: an overview.
AB  - One of the biggest challenges of performing dermatologic surgery procedures is to
      minimize pain. Not only will the experience of each patient be enhanced by
      increased comfort, but the medical and aesthetic results achieved by the
      physician will be facilitated as well. Iontophoresis is the use of electrical
      impulses to drive molecules into the skin. Anesthetic agents are one type of
      medicine that can be delivered in such a way. There is a tremendous potential for
      the applications of iontophoresis to be expanded. As our understanding of the
      technique increases we will be able to modify the skin's surface as well as the
      individual agents we wish to transport.

PMID- 11849265
TI  - The epidermal and dermal changes associated with microdermabrasion.
AB  - BACKGROUND: Microdermabrasion has become a popular method of skin rejuvenation
      for treating dyschromia, fine wrinkles, and mild scarring. OBJECTIVE: To analyze
      the onset and extent of the dermatologic changes associated with
      microdermabrasion. METHODS: Ten volunteers, ages 31-62 years, underwent a series
      of six aluminum oxide microdermabrasion facial treatments 7-10 days apart. Skin
      biopsy specimens were obtained prior to the study, after three treatments, and
      after six treatments. RESULTS: Compared to the controls, the treated areas
      demonstrated the following histologic changes: thickening of the epidermis and
      dermis, flattening of the rete pegs, vascular ectasia and perivascular
      inflammation, and hyalinization of the papillary dermis with newly deposited
      collagen and elastic fibers. CONCLUSION: This study suggests that
      microdermabrasion produces clinical improvement by a mechanism resembling a
      reparative process at the dermal and epidermal levels.

PMID- 11849266
TI  - Cost of nonmelanoma skin cancer treatment in the United States.
AB  - BACKGROUND: Despite being the most prevalent form of cancer, the economic impact
      of nonmelanoma skin cancer (NMSC) in the United States has not been assessed.
      OBJECTIVE: To determine the overall cost and to estimate the cost per episode of
      NMSC care in the United States in physicians' offices, outpatient surgery
      centers, and inpatient settings. METHODS: Data from the Medicare Current
      Beneficiary Study 1992-1995 were analyzed to obtain the total cost of NMSC and
      the cost in different settings. To normalize these data on a per episode basis,
      the cost in each setting was divided by the number of procedures performed in
      each setting obtained from the National Hospital Discharge Survey (NHDS, 1992
      1997), the National Survey of Ambulatory Surgery (NSAS, 1994-1996), and the
      National Ambulatory Medical Care Survey (NAMCS, 1995). RESULTS: The total cost of
      NMSC care in the United States in the Medicare population is $426 million/year.
      Physician office-based procedures for NMSC accounted for the greatest percentage
      of money spent to treat NMSC and the greatest percentage of procedures. The
      average cost per episode of NMSC when performed in a physician's office setting
      was found to be $492. The cost per episode of care in inpatient and outpatient
      settings were $5537 and $1043, respectively. CONCLUSION: Compared to other
      cancers, the relative magnitude of NMSC treatment costs is currently small
      because NMSC is managed efficiently and effectively, primarily in office-based
      settings. Legislative or regulatory measures that discourage office treatment of
      NMSC will lead to increased cost.

PMID- 11849267
TI  - Digitally processed ultraviolet images: a convenient, affordable, reproducible
      means of illustrating ultraviolet clinical examination.

PMID- 11849268
TI  - A simple tool for teaching flap design with digital images.
AB  - BACKGROUND: Defects created by excision or Mohs micrographic surgery must be
      analyzed and surgical options including flaps must be considered. Teaching flap
      design to dermatology trainees is often done at the bedside of the patient with
      the trainee describing or marking a proposed flap. Open discussion of the options
      in this way is sometimes unnerving for the patient. Blackboard discussions or
      drawings are limited in their realism. OBJECTIVE: To describe a rapid, simple
      method using commonly available software to allow a trainee to draw and redraw a
      proposed flap on a digital image of the defect without the time and cost of
      printing. METHODS: We describe a feature in the widely used presentation program
      Microsoft PowerPoint which can be used to draw on an imported digital image in
      various colors. RESULTS: A digital photograph taken at the bedside can quickly be
      loaded into PowerPoint and viewed as a full-screen picture on a computer. Using
      an electronic pen, multiple lines can be drawn and erased on the picture,
      allowing surgical planning and teaching away from the bedside. CONCLUSION: Design
      and analysis of potential incision lines for a flap can be done quickly using a
      digital image and commonly available software, allowing a new option for teaching
      flap design.

PMID- 11849270
TI  - Hatchet flap.

PMID- 11849269
TI  - Mucoepidermoid/adenosquamous carcinoma of the skin: presentation of two cases.
AB  - BACKGROUND: Mucoepidermoid carcinoma is a relatively common neoplasm of the major
      and minor salivary glands comprising 10-30% of primary carcinomas. They may
      involve the skin through direct extension, metastases, and rarely, as a primary
      focus (adenosquamous carcinoma). OBJECTIVE: To discuss through case reports, the
      nomenclature, histology, clinical course, and treatment of
      mucoepidermoid/adenosquamous carcinoma. METHODS: We present a case of
      mucoepidermoid carcinoma primary to an upper eyelid accessory lacrimal gland with
      direct cutaneous extension and a case of primary cutaneous adenosquamous
      carcinoma of the scalp. RESULTS: An eyelid neoplasm of lacrimal origin was
      initially treated with Mohs micrographic surgery (MMS), requiring an orbital
      exenteration to achieve a tumor-free plane. In the second case, a primary scalp
      lesion was cleared with MMS. Neither patient has had local recurrence or
      metastases. CONCLUSION: Correct diagnosis is crucial to pursuing adequate
      treatment for this aggressive neoplasm. We support the use of MMS to achieve
      local control.

PMID- 11849271
TI  - Use of an insulated ultrafine-point electrocautery for transconjunctival
      blepharoplasty of the lower eyelids.

PMID- 11849290
TI  - Dopaminergic signalling in the rodent neonatal suprachiasmatic nucleus identifies
      a role for protein kinase A and mitogen-activated protein kinase in circadian
      entrainment.
AB  - The circadian clock of the suprachiasmatic nuclei (SCN) of perinatal rodents is
      entrained by maternally derived cues. The SCN of neonatal Syrian hamsters express
      high-affinity D1 dopamine receptors, and the circadian activity-rest cycle of
      pups can be entrained by maternal injection of dopaminergic agonists. The present
      study sought to characterize the intracellular pathways mediating dopaminergic
      signalling in neonatal rodent SCN. Both dopamine and the D1 agonist SKF81297
      caused a dose-dependent increase in phosphorylation of the transcriptional
      regulator Ca2+/cyclic AMP response element (CRE) binding protein (CREB) in
      suprachiasmatic GABA-immunoreactive (-IR) neurons held in primary culture. The D1
      antagonist SCH23390 blocked this effect. Dopaminergic induction of pCREB-IR in
      GABA-IR neurons was also blocked by a protein kinase A (PKA) inhibitor, 5-24, and
      by the MAPK inhibitor, PD98059, whereas KN-62, an inhibitor of Ca2+/calmodulin
      dependent (CAM) kinase II/IV was ineffective. Treatment with NMDA increased the
      level of intracellular Ca2+ in the cultured primary SCN neurons in Mg2+-free
      medium, but SKF81297 did not. Blockade of CaM kinase II/IV with KN-62 inhibited
      glutamatergic induction of pCREB-IR in GABA-IR neurons, whereas 5-24 was
      ineffective, confirming the independent action of Ca2+- and cAMP-mediated inputs
      on pCREB. SKF81297 caused an increase in pERK-IR in SCN cells, and this was
      blocked by 5-24, indicative of activation of MAPK via D1/cAMP. These results
      demonstrate that dopaminergic signalling in the neonatal SCN is mediated via the
      D1-dependent activation of PKA and MAPK, and that this is independent of the
      glutamatergic regulation via Ca2+ and CaM kinase II/IV responsible for
      entrainment to the light/dark cycle.

PMID- 11849291
TI  - Postnatal maturation of Na+, K+, 2Cl- cotransporter expression and inhibitory
      synaptogenesis in the rat hippocampus: an immunocytochemical analysis.
AB  - GABA, a major inhibitory neurotransmitter, depolarizes hippocampal pyramidal
      neurons during the first postnatal week. These depolarizations result from an
      efflux of Cl- through GABAA-gated anion channels. The outward Cl- gradient that
      provides the driving force for Cl- efflux might be generated and maintained by
      the Na+, K+, 2Cl- cotransporter (NKCC) that keeps intracellular Cl- concentration
      above electrochemical equilibrium. The developmental pattern of expression of the
      cotransporter in the hippocampus is not known. We studied the postnatal
      distribution pattern of NKCC in the hippocampus using a monoclonal antibody (T4)
      against a conserved epitope in the C-terminus of the cotransporter molecule. We
      also examined the temporal relationships between the developmental pattern of
      NKCC expression and the formation of perisomatic GABAergic synapses. This study
      was aimed at determining, with antivesicular inhibitory amino acid transporter
      (VIAAT) antibodies, whether perisomatic GABAergic synapses are formed
      preferentially at the time when GABA is depolarizing. During the first postnatal
      week, NKCC immunolabelling was restricted to cell bodies in the pyramidal cell
      layer and in the strata oriens and radiatum. In contrast, at postnatal day 21
      (P21) and in adult animals little or no labelling occurred in cell bodies;
      instead, a prominent dendritic labelling appeared in both pyramidal and
      nonpyramidal neurons. The ultrastructural immunogold study in P21 rat hippocampi
      corroborated the light-microscopy results. In addition, this study revealed that
      a portion of the silver-intensified colloidal gold particles were located on
      neuronal plasmalemma, as expected for a functional cotransporter. The formation
      of inhibitory synapses on perikarya of the pyramidal cell layer was a late
      process. The density of VIAAT-immunoreactive puncta in the stratum pyramidale at
      P21 reached four times the P7 value in CA3, and six times the P7 value in CA1.
      Electron microscopy revealed that the number of synapses per neuronal perikaryal
      profile in the stratum pyramidale of the CA3 area at P21 was three times higher
      than at P7, even if a concomitant 20% increase in the area of these neuronal
      perikaryal profiles occurred. It is concluded that, in hippocampal pyramidal
      cells, there is a developmental shift in the NKCC localization from a
      predominantly somatic to a predominantly dendritic location. The presence of NKCC
      during the first postnatal week is consistent with the hypothesis that this
      transporter might be involved in the depolarizing effects of GABA. The
      depolarizing effects of GABA may not be required for the establishment of the
      majority of GABAergic synapses in the stratum pyramidale, because their number
      increases after the first postnatal week, when GABA action becomes
      hyperpolarizing.

PMID- 11849292
TI  - Brain catecholamine metabolism in catechol-O-methyltransferase (COMT)-deficient
      mice.
AB  - Catechol-O-methyltransferase (COMT) catalyses the O-methylation of compounds
      having a catechol structure and its main function involves the elimination of
      biologically active or toxic catechols and their metabolites. By means of
      homologous recombination in embryonic stem cells, a strain of mice has been
      produced in which the gene encoding the COMT enzyme is disrupted. We report here
      the levels of catecholamines and their metabolites in striatal extracellular
      fluid in these mice as well as in homogenates from different parts of the brain,
      under normal conditions and after acute levodopa administration. In
      immunoblotting studies, COMT-knockout mice had no COMT protein in brain or kidney
      tissues but the amounts of catecholamine synthesizing and other metabolizing
      enzyme proteins were normal. Under normal conditions, COMT deficiency does not
      appear to affect significantly brain dopamine and noradrenaline levels in spite
      of relevant changes in their metabolites. This finding is consistent with
      previous pharmacological studies with COMT inhibitors and confirms the pivotal
      role of synaptic reuptake processes and monoamine oxidase-dependent metabolism in
      terminating the actions of catecholamines at nerve terminals. In contrast, when
      COMT-deficient mice are challenged with l-dihydroxyphenylalanine, they show an
      extensive accumulation of 3,4-dihydroxyphenylacetic acid and
      dihydroxyphenylglycol and even dopamine, revealing an important role for COMT
      under such situations. Notably, in some cases these changes appear to be Comt
      gene dosage-dependent, brain-region specific and sexually dimorphic. Our results
      may have implications for improving the treatment of Parkinson's disease and for
      understanding the contribution of the natural variation in COMT activity to
      psychiatric phenotypes.

PMID- 11849294
TI  - Alterations in trkB mRNA in the human prefrontal cortex throughout the lifespan.
AB  - Signalling through tyrosine kinase receptor B (trkB) influences neuronal
      survival, differentiation and synaptogenesis. trkB exists in a full-length form
      (trkB(TK+)), which contains a catalytic tyrosine kinase (TK) domain, and a
      truncated form (trkB(TK-)), which lacks this domain. In the rodent brain,
      expression of trkB(TK+) decreases and trkBTK- increases during postnatal life. We
      hypothesized that both forms of trkB receptor mRNA would be present in the human
      neocortex and that the developmental profile of trkB gene expression in human may
      be distinct from that in rodent. We detected both trkB(TK+) and trkB(TK-) mRNA in
      RNA extracted from multiple human brain regions by Northern blot. Using in situ
      hybridization, we found trkB(TK+) mRNA in all cortical layers, with highest
      expression in layer IV and intermediate-to-high expression in layers III and V of
      the human dorsolateral prefrontal cortex. trkB(TK+) mRNA was present in neurons
      with both pyramidal and nonpyramidal shapes in the dorsolateral prefrontal
      cortex. trkB(TK+) mRNA levels were significantly increased in layer III in young
      adults as compared with infants and the elderly. In the elderly, trkB(TK+) mRNA
      levels were reduced markedly in all cortical layers. Unlike the mRNA encoding the
      full-length form of trkB, trkB(TK-) mRNA was distributed homogeneously across the
      grey matter, and trkB(TK-) mRNA levels increased only slightly during postnatal
      life. The results suggest that neurons in the human dorsolateral prefrontal
      cortex are responsive to neurotrophins throughout postnatal life and that this
      responsiveness may be modulated during the human lifespan.

PMID- 11849293
TI  - Mu and kappa opioid agonists modulate ventral tegmental area input to the ventral
      pallidum.
AB  - The ventral pallidum (VP) is situated at the convergence of midbrain dopamine and
      accumbal opioid efferent projections. Using in vivo electrophysiological
      procedures in chloral hydrate-anaesthetized rats, we examined whether discrete
      application of mu- [D-Ala2,N-Me-Phe4,Gly-ol5 (DAMGO)] or kappa- (U50488) opioid
      receptor agonists could alter VP responses to electrical stimulation of ventral
      tegmental area. Rate suppressions occurred frequently following ventral tegmental
      area stimulation. Consistent with an involvement of dopamine in this effect, none
      of the 12 spontaneously active ventral pallidal neurons recorded in rats that had
      monoamines depleted by reserpine responded to electrical stimulation of ventral
      tegmental area. Moreover, in intact rats, the dopamine antagonist flupenthixol
      attenuated evoked suppression in 100% of the neurons tested; however, the GABAA
      antagonist bicuculline was able to slightly attenuate the response in 50% of the
      neurons tested. These observations concur with our previous studies in indicating
      that ventral tegmental area stimulation releases dopamine (and sometimes GABA)
      onto ventral pallidal neurons. Both DAMGO and U50488 decreased the inhibitory
      effects of ventral tegmental area stimulation. These effects on the endogenously
      released transmitter differed from those seen with exogenously applied dopamine,
      for DAMGO did not alter the efficacy or potency of microiontophoretically applied
      dopamine. Taken together, these observations suggest that the interaction between
      DAMGO and dopamine does not occur at a site that is immediately postsynaptic to
      the dopaminergic input within the VP, but rather that opioid modulation involves
      mechanisms governing presynaptically released dopamine. These modulatory
      processes would enable ventral pallidal opioids to gate the influence of ventral
      tegmental area dopamine transmission on limbic system outputs at the level of the
      VP.

PMID- 11849295
TI  - A peripheral nervous system actin-binding protein regulates neurite outgrowth.
AB  - Difference cloning has identified a Villin-like mRNA transcript expressed
      selectively in peripheral sensory and sympathetic neurons. Pervin, the encoded
      820-amino acid protein, has 60% identity with Villin and is the rat homologue of
      Advillin. Coimmunoprecipitation studies demonstrate that Pervin and actin
      interact in vivo. Transfection of COS-7 epithelial cell lines demonstrates
      colocalization of epitope-tagged Pervin with green fluorescent protein-actin and
      results in an increase in process formation. This effect is abolished when the
      putative actin-bundling headpiece of Pervin is deleted. Biolistic transfection of
      primary cultures of rat dorsal root ganglion sensory neurons also results in
      increased neurite outgrowth with FLAG-tagged Pervin. Deletion of the actin
      bundling headpiece inhibits normal neurite growth. These data suggest that Pervin
      may play a significant role in regulating process outgrowth in peripheral neurons
      through a mechanism that involves the activity of an actin-bundling domain.

PMID- 11849296
TI  - Distinct localization of GABA(B) receptors relative to synaptic sites in the rat
      cerebellum and ventrobasal thalamus.
AB  - Metabotropic gamma-aminobutyric acid receptors (GABA(B)Rs) are involved in
      modulation of synaptic transmission and activity of cerebellar and thalamic
      neurons. We used subtype-specific antibodies in pre- and postembedding
      immunohistochemistry combined with three-dimensional reconstruction of labelled
      profiles and quantification of immunoparticles to reveal the subcellular
      distribution of pre- and postsynaptic GABA(B)R1a/b and GABA(B)R2 in the rat
      cerebellum and ventrobasal thalamus. GABA(B)R1a/b and R2 were extensively
      colocalized in most brain regions including the cerebellum and thalamus. In the
      cerebellum, immunoreactivity for both subtypes was prevalent in the molecular
      layer. The most intense immunoreactivity was found in Purkinje cell spines with a
      high density of immunoparticles at extrasynaptic sites peaking at around 240 nm
      from glutamatergic synapses between spines and parallel fibre varicosities. This
      is in contrast to dendrites at sites around GABAergic synapses where sparse and
      random distribution was found for both subtypes. In addition, more than one-tenth
      of the synaptic membrane specialization of spine-parallel fibre synapses were
      labelled at pre- or postsynaptic sites. Weak immunolabelling for both subtypes
      was also seen in parallel fibres but only rarely in GABAergic axons. In the
      ventrobasal thalamus, immunolabelling for both receptor subtypes was intense over
      the dendritic field of thalamocortical cells. Electron microscopy demonstrated an
      extrasynaptic localization of GABA(B)R1a/b and R2 exclusively in postsynaptic
      elements. Quantitative analysis further revealed the density of GABA(B)R1a/b
      around GABAergic synapses was higher than glutamatergic synapses on
      thalamocortical cell dendrites. The distinct localization of GABA(B)Rs relative
      to synaptic sites in the cerebellum and ventrobasal thalamus suggests that
      GABA(B)Rs differentially regulate activity of different neuronal populations.

PMID- 11849297
TI  - Knocking out the glial glutamate transporter GLT-1 reduces glutamate uptake but
      does not affect hippocampal glutamate dynamics in early simulated ischaemia.
AB  - Glutamate release in ischaemia triggers neuronal death. The major glial glutamate
      transporter, GLT-1, might protect against glutamate-evoked death by removing
      extracellular glutamate, or contribute to death by reversing and releasing
      glutamate. Previous studies of the role of GLT-1 in ischaemia have often used the
      GLT-1 blocker dihydrokainate at concentrations that affect transporters other
      than GLT-1 and which affect kainate, N-methyl-D-aspartate (NMDA) and alpha-amino
      3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors. In hippocampal
      slices from postnatal day 14 mice lacking GLT-1, the current response of area CA1
      pyramidal cells to superfused AMPA and NMDA (which are not taken up) was
      unaffected, whereas the response to 100 microm glutamate was more than doubled
      relative to that in wild-type littermates, a finding consistent with a decrease
      in glutamate uptake. In response to a few minutes of simulated ischaemia,
      pyramidal cells in wild-type mice showed a large and sudden inward glutamate
      evoked current [the anoxic depolarization (AD) current], which declined to a less
      inward plateau. In mice lacking GLT-1, the time to the occurrence of the AD
      current, its amplitude, the size of the subsequent plateau current and the block
      of the plateau current by glutamate receptor blockers were all indistinguishable
      from those in wild-type mice. We conclude that GLT-1 does not contribute
      significantly to glutamate release or glutamate removal from the extracellular
      space in early simulated ischaemia. These data are consistent with glutamate
      release being by reversal of neuronal transporters, and with uptake into glia
      being compromised by the ischaemia-evoked fall in the level of ATP needed to
      convert glutamate into glutamine.

PMID- 11849298
TI  - Orexin receptor-1 (OX-R1) immunoreactivity in chemically identified neurons of
      the hypothalamus: focus on orexin targets involved in control of food and water
      intake.
AB  - The neuropeptides orexin-A and orexin-B are produced in neurons of the lateral
      hypothalamic area and have been implicated to be involved in the regulation of
      food/water intake and sleep-wake control. The orexins act at two different G
      protein-coupled orexin receptors (OX-R1 and OX-R2) that are derived from separate
      genes and expressed differentially throughout the central nervous system. In the
      present study, we have used a polyclonal antipeptide antiserum to analyse in
      detail the distribution of OX-R1-immunoreactive neurons in the rat hypothalamus.
      In order to identify the chemical mediators of orexin action in the hypothalamus,
      the OX-R1-containing neurons were characterized with regard to the content of
      peptides shown previously to affect ingestive and drinking behaviour. Neurons
      containing OX-R1 immunoreactivity were widely distributed in the hypothalamus
      with cell bodies located in the suprachiasmatic, periventricular, paraventricular
      (both magno- and parvocellular division), supraoptic, arcuate, ventromedial,
      dorsomedial and tuberomammillary nuclei and the lateral hypothalamic area. In
      magnocellular neurons of the paraventricular and supraoptic nuclei, OX-R1
      immunoreactivity was seen in both vasopressin- and oxytocin-containing neurons.
      OX-R1 immunoreactivity was demonstrated in vasopressin and vasoactive intestinal
      polypeptide (VIP) neurons of the suprachiasmatic nucleus, in somatostatin neurons
      of the periventricular nucleus and in corticotropin-releasing hormone (CRH)
      neurons of the parvocellular paraventricular nucleus. In the arcuate nucleus, OX
      R1 immunoreactivity was present in neuropeptide Y (NPY) and agouti-related
      peptide (AGRP) neurons of the ventromedial part as well as in proopiomelanocortin
      (POMC) and cocaine- and amphetamine-regulated transcript (CART) neurons of the
      ventrolateral division. In the lateral hypothalamic area, OX-R1 immunoreactivity
      was demonstrated in melanin-concentrating hormone (MCH)- and orexin-containing
      neurons. In the hypothalamic tuberomammillary nucleus, OX-R1-immunoreactivity was
      shown in many histamine-containing neurons. The results support the idea that
      orexins have important actions on hypothalamic neurons that control food intake
      and fluid balance, but also that orexins may regulate other neuroendocrine
      systems.

PMID- 11849299
TI  - The expression of Fos following kainic acid-induced seizures is age-dependent.
AB  - The expression of limbic seizures following kainic acid (KA) administration
      starts at approximately postnatal day (P) 19 in rats. In this study we
      investigated whether the expression of Fos-like immunoreactivity (Fos-IR) in
      limbic regions occurs concomitantly with the behavioural expression of limbic
      seizures. Immunohistochemistry for c-Fos protein was examined 1, 2, 4, 12 and 24
      h following seizure onset (KA-treated rats) or saline injections (controls) in
      immature and adult rats at P7, P13, P20 and P60. The expression of Fos-IR in
      limbic structures following KA-induced seizures is age-dependent. There is a
      strong and selective induction of Fos-IR in the CA3 region of the hippocampus
      following KA-induced seizures in rats at P7. However, the expression of Fos-IR in
      KA-treated rats at P13, P20 and P60 involved other hippocampal structures in
      addition to CA3. Abundant induction of Fos-IR was found in the CA1, CA3 and
      dentate gyrus (DG) in KA-treated rats at P13, P20 and P60. While immature rats at
      P7 and P13 showed very few or no Fos-IR neurons in most amygdala nuclei, rat pups
      at P20 showed strong induction of Fos-IR in the amygdala. Our results
      demonstrated that the induction of Fos-IR in most amygdala nuclei and the full
      expression of behavioural limbic seizures occur at the same developmental age,
      which is consistent with the idea that the amygdala may play a role in the
      modulation of limbic seizures.

PMID- 11849300
TI  - Magnetic oscillatory responses to lateralization changes of natural and
      artificial sounds in humans.
AB  - Oscillatory signals in human magnetoencephalogram were investigated as correlates
      of cortical network activity in response to sound lateralization changes.
      Previously, we found lateralized presentations of a monosyllabic word to elicit
      posterior temporo-parietal gamma-band activity, possibly reflecting
      synchronization of neuronal assemblies in putative auditory dorsal stream areas.
      In addition, beta activity was decreased over sensorimotor regions, suggesting
      the activation of motor networks involved in orientating. The present study
      investigated responses to lateralization changes of both a barking dog sound and
      a distorted noise to test whether beta desynchronization would depend on the
      sound's relevance for orientating. Eighteen adults listened passively to 900
      samples of each sound in separate location mismatch paradigms with midline
      standards and both right- and left-lateralized deviants. Lateralized distorted
      noises were accompanied by enhanced spectral amplitude at 58-73 Hz over right
      temporo-parietal cortex. Left-lateralized barking dog sounds elicited right and
      right-lateralized sounds elicited bilateral temporo-parietal spectral amplitude
      increases at approximately 77 Hz. This replicated the involvement of posterior
      temporo-parietal areas in auditory spatial processing. Only barking dog sounds,
      but not distorted noises, gave rise to 30 Hz desynchronization over contralateral
      sensorimotor areas, parieto-frontal gamma coherence increases and beta coherence
      reductions between sensorimotor and prefrontal sensors. Apparently passive
      listening to lateralized natural sounds with a potential biological relevance led
      to an activation of motor networks involved in the automatic preparation for
      orientating. Parieto-frontal coherence increases may reflect enhanced coupling of
      networks involved in the integration of auditory spatial and motor processes.

PMID- 11849301
TI  - The organization of visual object representations: a connectionist model of
      effects of lesions in perirhinal cortex.
AB  - We have developed a simple connectionist model based on the idea that perirhinal
      cortex has properties similar to other regions in the ventral visual stream, or
      'what' pathway. The model is based on the assumption that representations in the
      ventral visual stream are organized hierarchically, such that representations of
      simple features of objects are stored in caudal regions of the ventral visual
      stream, and representations of the conjunctions of these features are stored in
      more rostral regions. We propose that a function of these feature conjunction
      representations is to help to resolve 'feature ambiguity', a property of visual
      discrimination problems that can emerge when features of an object predict a
      given outcome (e.g. reward) when part of one object, but predict a different
      outcome when part of another object. Several recently reported effects of lesions
      of perirhinal cortex in monkeys have provided key insights into the functions of
      this region. In the present study these effects were simulated by comparing the
      performance of connectionist networks before and after removal of a layer of
      units corresponding to perirhinal cortex. The results of these simulations
      suggest that effects of lesions in perirhinal cortex on visual discrimination may
      be due not to the impairment of a specific type of learning or memory, such as
      declarative or procedural, but to compromising the representations of visual
      stimuli. Furthermore, we propose that attempting to classify perirhinal cortex
      function as either 'perceptual' or 'mnemonic' may be misguided, as it seems
      unlikely that these broad constructs will map neatly onto anatomically defined
      regions of the brain.

PMID- 11849302
TI  - Perirhinal cortex resolves feature ambiguity in complex visual discriminations.
AB  - The present experiment tested predictions of a 'perceptual-mnemonic/feature
      conjunction' (PMFC) model of perirhinal cortex function. The model predicts that
      lesions of perirhinal cortex should disrupt complex visual discriminations with a
      high degree of 'feature ambiguity', a property of visual discrimination problems
      that can emerge when features of an object are rewarded when they are part of one
      object, but not when part of another. As feature ambiguity is thought to be the
      critical factor, such effects should be independent of the number of objects to
      be discriminated. This was tested directly, by assessing performance of control
      monkeys and monkeys with aspiration lesions of perirhinal cortex on a series of
      concurrent discriminations in which the number of object pairs was held constant,
      but the degree of feature ambiguity was varied systematically. Monkeys were
      tested in three conditions: Maximum Feature Ambiguity, in which all features were
      explicitly ambiguous (AB+, CD+, BC-, AD-; the biconditional problem); Minimum
      Feature Ambiguity, in which no features were explicitly ambiguous (AB+, CD+, EF-,
      GH-); and Intermediate Feature Ambiguity, in which half the features were
      explicitly ambiguous (AB+, CD+, CE-, AF-). The pattern of results closely matched
      that predicted by simulations using a connectionist network: monkeys with
      perirhinal cortex lesions were unimpaired in the Minimum Feature Ambiguity
      condition, mildly impaired in the Intermediate Feature Ambiguity condition and
      severely impaired in the Maximum Feature Ambiguity condition. These results
      confirm the predictions of the PMFC model, and force a reconsideration of
      prevailing views regarding perirhinal cortex function.

PMID- 11849303
TI  - Alpha-adrenoreceptor activation modulates swimming via glycinergic and GABAergic
      inhibitory pathways in Xenopus laevis tadpoles.
AB  - This study focuses upon the network pathways underlying the adrenoreceptor
      mediated modulation of fictive swimming in the immobilized Xenopus laevis
      tadpole. As shown recently, noradrenaline (NA) increases cycle periods while
      simultaneously reducing the rostrocaudal delay in head-to-tail firing and the
      duration of swimming episodes. Furthermore, both swimming frequency and duration
      are reduced by selective pharmacological activation of alpha1- and/or alpha2
      adrenoreceptors, while alpha1-receptor activation also reduces rostrocaudal
      delays. We show that NA could still modulate aspects of swimming after blocking
      either glycine or GABA(A) receptors with strychnine and bicuculline,
      respectively. Furthermore, after prior application of NA, strychnine could
      counteract noradrenergic effects on cycle periods and rostrocaudal delays, while
      bicuculline could counteract effects on cycle periods, suggesting that these two
      fast inhibitory pathways are both involved in the NA modulation of swimming. In
      addition, blocking glycine receptors reduced the effects of alpha1-receptors on
      cycle periods and delays, while blocking GABA(A) receptors had no effect.
      Blocking either glycine or GABA(A) receptors, however, lessened the reduction in
      swimming frequency by alpha2-receptors. In addition, pre-application of
      bicuculline prevented a reduction in episode durations by NA, alpha1- and alpha2
      receptors. Our findings suggest that the noradrenergic modulation of Xenopus
      swimming is mediated via alpha-adrenoreceptors interacting with both glycinergic
      and GABAergic inhibitory pathways. Both alpha1- and alpha2-receptor activation
      influences the GABAergic pathway controlling the duration of swimming episodes
      and is involved in the glycinergic modulation of the swimming rhythm and its
      longitudinal co-ordination, with alpha2-receptors additionally affecting swimming
      frequency through GABAergic pathways.

PMID- 11849304
TI  - Forced swimming triggers vasopressin release within the amygdala to modulate
      stress-coping strategies in rats.
AB  - Previously, we have demonstrated that forced swimming triggers the release of
      arginine vasopressin (AVP) within the septum of rats, where AVP modulates stress
      coping strategies. The present study was designed to examine the effects of
      forced swimming on the release of AVP within the amygdala. Therefore, adult male
      Wistar rats were chronically implanted with a microdialysis probe aimed at the
      amygdala to monitor the local release of AVP under both resting and stress
      conditions. A 10-min forced swimming session caused a significant increase in the
      extracellular AVP concentration (to 366 +/- 90% of baseline; P < 0.05) within
      this brain area. In a subsequent experiment we investigated the physiological
      impact of the stressor-induced release of AVP by administrating the AVP V1
      receptor antagonist d(CH2)5Tyr(Me)AVP into the amygdala via inverse
      microdialysis. Bilateral antagonist treatment modulated the behavioural response
      acutely by increasing the time the animals spent struggling and by reducing the
      time the animals floated. Our results demonstrate a significant activation of the
      vasopressinergic system within the amygdala in response to forced swimming. AVP
      released within the amygdala seems to be involved in the generation of passive
      coping strategies in stressful situations. Taken together with previous findings
      the results of the present study suggest that AVP is released within septum and
      amygdala to balance the behavioural response during forced swimming.

PMID- 11849305
TI  - Bilateral overactivation of the sensorimotor cortex in the unilateral rodent
      model of Parkinson's disease - a functional magnetic resonance imaging study.
AB  - Functional magnetic resonance imaging (fMRI) is used to investigate the basal
      ganglia (BG)-cortex circuit using a rat model of Parkinson's disease (PD). The
      model involves a unilateral destruction of the right substantia nigra by
      intranigral injection of the dopaminergic neurotoxin 6-hydroxydopamine. Volume of
      cortical activity was measured by the blood oxygenation level-dependent contrast
      method while applying electrical forepaw stimulation. The main findings are the
      following. (i) Contrary to the predictions of the classic model but in line with
      recent experimental results (positron emission tomography, fMRI and
      electrophysiology), an increased cortical activity in the sensorimotor cortex of
      PD rats compared with sham-operated or normal rats was found. (ii) A diffuse
      neuronal activity at large cortical areas that were not related directly to the
      stimulation used, was observed. (iii) No difference was found between the lesion
      and the nonlesion hemispheres when the left or the right forepaw was stimulated;
      both cortices show significant overactivation of the sensorimotor cortices in
      addition to diffuse cortical activation. The last finding could be explained by
      either corticocortical connections or by bilateral BG-cortex connections. These
      finding suggest that the mutual influence of the two hemispheres is important in
      the pathophysiology of the BG-cortex circuit and might be crucial in predicting
      treatments.

PMID- 11849306
TI  - The human startle reflex and pons activation: a regional cerebral blood flow
      study.
AB  - Using positron emission tomographic measurements of regional cerebral blood flow,
      we report activation of a medial pons area in humans during acoustic startle
      stimulation. Eight healthy volunteers were scanned during rest and when presented
      startle-eliciting stimuli. We performed a theory-driven directed search for
      activity in the nucleus reticularis pontis caudalis, situated in the pons.
      Because habituation of cerebellar activity during acoustic startle repetition has
      been reported [Timmann, D., Musso, C., Kolb, F.P., Rijntjes, M., Juptner, M.,
      Muller, S.P., Diener, H.C. & Weiller, C. (1998) J. Neurol. Neurosurg. Psychiatry
      65, 771-773], we also predicted habituation in the cerebellum and in the pons as
      a function of startle repetition. Measurements of eye electromyography validated
      the presence of a startle response and its habituation. Analysis of regional
      cerebral blood flow revealed higher neural activity during startle stimulation
      than at rest in a medial pons area consistent with the location of the pontine
      reticular nucleus. As a consequence of startle repetition, regional cerebral
      blood flow increased in the medial cerebellum, and habituated in the ventral
      cerebellum and in a ventral pons area separate from the pontine reticular
      nucleus. In the ventral pons, but not in the pontine reticular nucleus, regional
      cerebral blood flow and the startle reflex were positively correlated. In the
      cerebellum both positive and negative correlations with the startle reflex were
      observed. Thus we conclude that the neurofunctional correlates of the startle
      circuit and its habituation in humans are similar to that previously described in
      animals.

PMID- 11849307
TI  - Speech listening specifically modulates the excitability of tongue muscles: a TMS
      study.
AB  - The precise neural mechanisms underlying speech perception are still to a large
      extent unknown. The most accepted view is that speech perception depends on
      auditory-cognitive mechanisms specifically devoted to the analysis of speech
      sounds. An alternative view is that, crucial for speech perception, it is the
      activation of the articulatory (motor) gestures that generate these sounds. The
      listener understands the speaker when his/her articulatory gestures are activated
      (motor theory of speech perception). Here, by using transcranial magnetic
      stimulation (TMS), we demonstrate that, during speech listening, there is an
      increase of motor-evoked potentials recorded from the listeners' tongue muscles
      when the presented words strongly involve, when pronounced, tongue movements.
      Although these data do not prove the motor theory of speech perception, they
      demonstrate for the first time that word listening produces a phoneme specific
      activation of speech motor centres.

PMID- 11849308
TI  - Brain macrophages inhibit gap junctional communication and downregulate connexin
      43 expression in cultured astrocytes.
AB  - Astrocytes are typically interconnected by gap junction channels that allow, in
      vitro as well as in vivo, a high degree of intercellular communication between
      these glial cells. Using cocultures of astrocytes and neurons, we have
      demonstrated that gap junctional communication (GJC) and connexin 43 (Cx43)
      expression, the major junctional protein in astrocytes, are controlled by
      neuronal activity. Moreover, neuronal death downregulates these two parameters.
      Because in several brain pathologies neuronal loss is associated with an increase
      in brain macrophage (BM) density, we have now investigated whether coculture with
      BM affects astrocyte gap junctions. We report here that addition of BM for 24 h
      decreases the expression of GJC and Cx43 in astrocytes in a density-dependent
      manner. In contrast, Cx43 is not detected in BM and no heterotypic coupling is
      observed between the two cell types. A soluble factor does not seem to be
      involved in these inhibitions because they are not observed either in the
      presence of BM conditioned media or in the absence of direct contact between the
      two cell types by using inserts. These observations could have pathophysiological
      relevance as neuronal death, microglial proliferation and astrocytic reactions
      occur in brain injuries and pathologies. Because astrocyte interactions with BM
      and dying neurons both result in the downregulation of Cx43 expression and in the
      inhibition of GJC, a critical consequence on astrocytic phenotype in those
      situations could be the inhibition of gap junctions.

PMID- 11849309
TI  - Tumour necrosis factor in mouse models of chronic intestinal inflammation.

PMID- 11849311
TI  - Prostaglandin and PPAR control of immune cell function.

PMID- 11849310
TI  - IgG4 breaking the rules.
AB  - Immunoglobulin G4 (IgG4) antibodies have been known for some time to be
      functionally monovalent. Recently, the structural basis for this monovalency has
      been elucidated: the in vivo exchange of IgG half-molecules (one H-plus one L
      chain) among IgG4. This process results in bispecific antibodies that in most
      situations will behave as functionally monovalent antibodies. The structural
      basis for the abnormal behaviour of IgG4 seems to be largely the result of a
      single amino acid change relative to human IgG1: the change of a proline in core
      hinge of IgG1 to serine. This results in a marked shift in the equilibrium
      between interchain disulphide bridges and intrachain disulphide bridges, which
      for IgG4 results in 25-75% absence of a covalent interaction between the H
      chains. Because of strong non-covalent interactions between the CH3 domains (and
      possibly also between the CH1 domain and the trans-CH2 domain) IgG4 is a stable
      four-chain molecule and does not easily exchange half-molecules under standard
      physiological conditions in vitro. We postulate that the exchange is catalysed in
      vivo by protein disulphide isomerase (PDI) and/or FcRn (the major
      histocompatibility complex (MHC)-related Fc receptor) during transit of IgG4 in
      the endosomal pathway in endothelial cells. Because IgG4 is predominantly
      expressed under conditions of chronic antigen exposure, the biological relevance
      of this exchange of half-molecules is that it generates antibodies that are
      unable to form large immune complexes and therefore have a low potential for
      inducing immune inflammation. In contrast to monovalent immunoglobulin fragments,
      these scrambled immunoglobulins have a normal half-life. The significance of the
      ensuing bispecificity needs further evaluation, because this will be relevant
      only in situations where high IgG4 responses are found to two unrelated antigens
      that happen to be present in the body at the same time and place. In this context
      the significance of IgG4 autoreactivity might have to be re-evaluated. The main
      function of IgG4, however, is presumably to interfere with immune inflammation
      induced by complement-fixing antibodies, or, in the case of helminth infection or
      allergy, by IgE antibodies.

PMID- 11849312
TI  - Prostaglandin D(2), its metabolite 15-d-PGJ(2), and peroxisome proliferator
      activated receptor-gamma agonists induce apoptosis in transformed, but not
      normal, human T lineage cells.
AB  - Prostaglandin D(2) (PGD(2)) is abundantly produced by mast cells, platelets, and
      alveolar macrophages and has been proposed as a key immunoregulatory lipid
      mediator. 15-Deoxy-Delta(12,14)-PGJ(2) (15-d-PGJ(2)), a key PGD(2) metabolite, is
      under intense study as a potential anti-inflammatory mediator. Little is known
      about PGD(2) or the role of 15-d-PGJ(2), if any, in regulating the activities of
      human T lineage cells. In this report we demonstrate that both PGD(2) and 15-d
      PGJ(2) have potent antiproliferative effects, and in fact kill human T lymphocyte
      lines derived from malignant cells by an apoptotic mechanism. Interestingly,
      normal human T cells were not similarly affected. Although the T lymphocyte lines
      express mRNA for the PGD(2) receptor (DP-R), a potent DP receptor agonist,
      BW245C, did not inhibit the proliferation or viability of the cells, suggesting
      an alternative mechanism of action. PGD(2) and 15-d-PGJ(2) can bind to the
      peroxisome proliferator activated receptor-gamma (PPAR-gamma) which is implicated
      in lipid metabolism and apoptosis. Exposure to synthetic PPAR-gamma ligands (e.g.
      ciglitazone, troglitazone) mimicked the inhibitory responses of PGD(2) and 15-d
      PGJ(2), and induced apoptosis in the transformed T cells consistent with a PPAR
      gamma-dependent mechanism. These observations suggest that PPAR-gamma ligands
      (which may include PGD2) provide strong apoptotic signals to transformed, but not
      normal T lymphocytes. Thus, the efficacy of utilizing PPAR-gamma and its ligands
      as therapeutics for human T cell cancers needs to be further evaluated.

PMID- 11849314
TI  - Influence of CD4 T cells and the source of major histocompatibility complex class
      II-restricted peptides on cytotoxic T-cell priming by dendritic cells.
AB  - We have previously reported that bone marrow derived dendritic cells (DC) pulsed
      with major histocompatibility complex (MHC) class I-restricted peptide
      efficiently prime a cytotoxic T lymphocyte (CTL) response in vivo. Here we assess
      the involvement of CD4(+) T cells in the induction of CD8(+) CTL by DC by testing
      the ability of class II-deficient (C2D) DC, class II mutant (Alpha beta mut) DC
      and autologous serum generated DC (AS DC) to present class I-restricted antigens
      in vitro and in vivo. DC generated from the bone marrow of class II knockout mice
      and transgenic mice expressing a mutant class II that can not bind CD4 were
      phenotypically similar to wild type (wt) DC, except with regard to MHC class II
      expression. The C2D and Alpha beta mut DC, though fully capable of presenting the
      class I-restricted ovalbumin (OVA) peptide to a T-cell hybridoma in vitro, failed
      to prime a CTL response in vivo. Restoration of class II expression on C2D DC
      allowed priming of a CTL response; thus, the defect in CTL priming was indeed
      caused by the absence of class II expression. Likewise, DC generated in
      autologous serum were unable to prime a CTL response as these DC only express
      'self' class II epitopes and therefore would not activate syngeneic CD4(+) T
      cells. Addition of exogenous class II epitopes rescued the ability of AS DC to
      prime a CTL response. These observations provide convincing evidence that
      efficient CTL induction by DC in vivo requires concomitant presentation of class
      II epitopes for CD4(+) T-cell induction.

PMID- 11849313
TI  - Signalling pathways induced by protease-activated receptors and integrins in T
      cells.
AB  - Recent characterization of the thrombin receptor indicates that it plays a role
      in T-cell signalling pathways. However, little is known regarding the signalling
      events following stimulation of additional members of the protease-activated
      receptor (PAR) family, i.e. PAR2 and PAR3. Most of the postligand cascades are
      largely unknown. Here, we illustrate that in Jurkat T-leukaemic cells, activation
      of PAR1, PAR2 and PAR3 induce tyrosine phosphorylation of Vav1. This response was
      impaired in Jurkat T cells deficient in p56lck (JCaM1.6). Activation of PARs also
      led to an increase in tyrosine phosphorylation of ZAP-70 and SLP-76, two key
      proteins in T-cell receptor (TCR) signalling. We also demonstrated that p56lck is
      meaningful for integrin signalling. Thus, JCaM1.6 cells exhibited a marked
      reduction in their adherence to fibronectin-coated plates, as compared to the
      level of adherence of Jurkat T cells. While the phosphorylation of Vav1 in T
      cells is augmented following adhesion, no additional increase was noted following
      treatment of the adhered cells with PARs. Altogether, we have identified key
      components in the postligand-signalling cascade of PARs and integrins.
      Furthermore, we have identified Lck as a critical and possibly upstream component
      of PAR-induced Vav1 phosphorylation, as well as integrin activation, in Jurkat T
      cells.

PMID- 11849315
TI  - Grass pollen immunotherapy for hayfever is associated with increases in local
      nasal but not peripheral Th1:Th2 cytokine ratios.
AB  - Grass pollen immunotherapy is the only treatment for hayfever that is both
      effective and confers long-term benefit. Immunotherapy may act by altering the
      local nasal mucosal T helper type 2 (Th2) to type 1 (Th1) cytokine balance either
      by down-regulation and/or immune deviation of T-lymphocyte responses. There is
      controversy as to whether these changes are detectable in peripheral blood. We
      therefore examined both local nasal and peripheral T-cell responses to allergen
      exposure in the same subjects before and after immunotherapy. In a double-blind
      trial of grass pollen immunotherapy, nasal biopsies were obtained at baseline and
      during the peak pollen season following 2 years of immunotherapy. Placebo-treated
      patients showed a seasonal increase in CD3(+) T cells (P = 0.02) and in
      interleukin-5 (IL-5) mRNA(+) cells (P = 0.03) and no change in interferon-gamma
      (IFN-gamma ) mRNA(+) cells (P = 0.2) in the nasal mucosa. In contrast, in the
      immunotherapy-treated group, there were no changes in the number of CD3(+) T
      cells (P = 0.3) and IL-5 mRNA+ cells (P = 0.2) but a significant increase in the
      number of IFN-gamma mRNA(+) cells (P = 0.03). Furthermore, clinical improvement
      in the immunotherapy-treated group was accompanied by a seasonal increase in the
      ratio of IFN-gamma to IL-5 mRNA(+) cells in the nasal mucosa (P = 0.03). In
      contrast, there were no significant changes in peripheral T-cell proliferative
      responses or cytokine production for IFN-gamma or IL-5 in response to grass
      pollen either within or between the two treatment groups. We conclude that
      successful grass pollen immunotherapy was associated with an increase in the
      ratio of IFN-gamma to IL-5 mRNA(+) cells in the nasal mucosa, whereas these
      changes were not reflected by alterations in peripheral blood T-cell
      proliferative responses or cytokine production before/after treatment.

PMID- 11849316
TI  - Murine graft-versus-host disease induced using interferon-gamma-deficient grafts
      features antibodies to double-stranded DNA, T helper 2-type cytokines and
      hypereosinophilia.
AB  - Acute, lethal graft-versus-host disease (GvHD) develops in B6D2F1 hybrid
      recipients of wild-type, C57BL/6, parental strain grafts; however, when
      interferon-gamma (IFN-gamma) gene knockout (gko) donors are used, the disease is
      prolonged and associated with a higher level of engraftment, particularly of T
      cells. Lesions containing large, mixed cellular infiltrates develop in the skin,
      liver, pancreas, salivary gland, lung and kidney. In our current study, we wished
      to determine whether GvHD features a preponderance of T helper 2 (Th2) cytokines
      in the absence of donor-derived IFN-gamma, and whether autoantibody production,
      commonly associated with chronic GvHD, also occurs. Because mitogen
      responsiveness is consistently suppressed in mice with acute GvHD, we wished to
      measure this response in recipients of IFN-gamma gko grafts. Our findings
      indicate that spleen cells from the latter produce interleukin (IL)-4, IL-5 and
      IL-13 in culture, but respond poorly to concanavalin A (Con A) and
      lipopolysaccharide (LPS). Their sera contain anti-nuclear antibodies (ANA), some
      of which are specific for double-stranded (ds)DNA and are predominantly
      immunoglobulin (Ig)M and IgG1. We also noted the presence of numerous eosinophils
      in the infiltrates developing within the target organs. In some respects, this
      syndrome bears resemblance to both systemic lupus erythematosus (SLE) and chronic
      GvHD. However, histological evidence of glomerulonephritis is lacking and
      proteinuria fails to develop in recipients of IFN-gamma gko grafts, suggesting
      that IFN-gamma may be necessary for the development of lupus nephritis. On a
      broader scope, our findings underscore the importance of IFN-gamma in the
      pathogenetic mechanism of GvHD, and demonstrate that the absence of this cytokine
      promotes the development of chronic GvHD and autoimmunity.

PMID- 11849317
TI  - Expression of matrix metalloproteinases and tissue inhibitors of
      metalloproteinases define the migratory characteristics of human monocyte-derived
      dendritic cells.
AB  - Dendritic cells (DCs) have an essential role in the initiation of immune
      responses as they deliver antigen/epitope and the appropriate signals to activate
      naive T cells and thus start an immune response. In order to fulfil their
      function, DCs have to patrol different part of the body, thus migrating through
      the extracellular matrix to sample the local 'antigenic' environment. In the
      present study, we have investigated which enzymes might be involved in this
      process using the Matrigel trans-well migration assay, an in vitro model of
      extracellular matrix migration. In this assay we analysed the migratory ability
      of interleukin-4 (IL-4)/granulocyte macrophage-colony-stimulating factor (GM-CSF)
      derived immature DCs as well as mature DCs, induced by tumour necrosis factor
      alpha (TNF-alpha) and modified vaccinia virus Ankara (MVA). The 'mature' DCs
      showed an increased migration through Matrigel, which was significantly inhibited
      by inhibitors of matrix metalloproteinases (MMP). We also observed that the
      dominant MMP involved in this process was MMP-9, and a concomitant decrease of
      the endogenous tissue inhibitors of metalloproteinases (TIMP)-1 and TIMP-2 was
      also observed. Collectively these data suggest that the balance between MMP/TIMP
      determines the net migratory capacity of human DCs. Surprisingly, TIMP-3 was
      significantly increased in mature DC. Our data thus indicate that MMP and TIMP
      play a role in the migratory ability of human DCs. Our results also suggest that
      TIMP-3 expression might represent a new marker of maturation of human DCs.

PMID- 11849318
TI  - Chloroquine decreases cell-surface expression of tumour necrosis factor receptors
      in human histiocytic U-937 cells.
AB  - Proinflammatory cytokine tumour necrosis factor (TNF) mediates its diverse
      effects through cell surface receptors. A variety of inflammatory signals are
      known to modulate TNF activities by changing expression and shedding of cell
      surface TNF receptors. We have examined the effects of anti-rheumatic drug
      chloroquine on the expression of cell surface and soluble TNF receptors in human
      histiocytic U-937 cells. Chloroquine partially reduced production of soluble p55
      and p75 TNF receptors in cells stimulated with phorbol 12-myristate 13-acetate
      (PMA). In these cells, induction of both TNF receptor mRNA was not changed and
      the levels of cell-associated TNF receptors were rather increased by chloroquine.
      Flow cytometric analysis revealed that chloroquine does not inhibit the PMA
      triggered shedding of TNF receptors from cell surface, while it was suppressed by
      a metalloproteinase inhibitor BB-3103. Treatment of U-937 cells with chloroquine
      significantly reduced the level of cell surface TNF receptors and a similar
      effect was observed with human peripheral blood monocytes. Other weak-base
      amines, including hydroxychloroquine, ammonium chloride and methylamine, also
      induced reduction of cell surface TNF receptors, whereas lysosomal proteinase
      inhibitor, leupeptin, and BB-3013 were without effect. Our results suggest that
      chloroquine down-regulates cell surface TNF receptors by retarding their
      transport to the cell surface, while cleavage of cell surface receptors is not
      inhibited by chloroquine.

PMID- 11849319
TI  - Inhibition of B16 melanoma experimental metastasis by interferon-gamma through
      direct inhibition of cell proliferation and activation of antitumour host
      mechanisms.
AB  - Interferon-gamma (IFN-gamma) has pleiotropic activities other than its antivirus
      action, including cell growth inhibition, natural killer (NK) cell and cytotoxic
      T lymphocyte (CTL) activation, and angiogenesis inhibitory activity, and these
      activities are supposed to be involved in its antitumour activity. However, it
      has not been completely elucidated which activity is mainly involved in the
      tumour suppression in vivo. In this study, we analysed inhibitory mechanisms of
      endogenous IFN-gamma against B16 melanoma experimental metastasis. After
      intravenous injection of tumour cells, tumour deposits in the lungs and liver
      were increased and life span was shorter in IFN-gamma(-/-) mice, indicating
      important roles for IFN-gamma in antitumour mechanisms. Interestingly, tumour
      deposits were not increased in IFN-gamma receptor (R)(-/-) mice. Furthermore,
      only low levels of cell-mediated immunity against the tumour and activation of NK
      cells were observed, indicating that antimetastatic effects of IFN-gamma is not
      mediated by host cells. The survival period of B16 melanoma-bearing IFN-gamma R(
      /-) mice was, however, shorter than wild-type mice. These observations suggest
      that IFN-gamma prevents B16 melanoma experimental metastasis by directly
      inhibiting the cell growth, although antitumour host functions may also be
      involved in a later phase.

PMID- 11849320
TI  - Epithelial cells respond to proteolytic and non-proteolytic detachment by
      enhancing interleukin-6 responses.
AB  - Intestinal inflammatory disease or infection often results in the loss of the
      epithelial layer as a result mainly of the action of proteases, including the
      leucocyte serine proteinases (neutrophil elastase), lysosomal cathepsins and the
      matrix metalloproteinases from recruited inflammatory cells. Previous studies
      have shown that bronchial or intestinal epithelial cells (IEC) can respond to
      proteolytic attack by producing cytokines. In this study, we have determined the
      effect of protease treatment on interleukin-6 (IL-6) and monocyte chemoattractant
      protein-1 (MCP-1) production by IEC lines. Both neutrophil elastase and trypsin
      treatment induced elevated levels of mRNA for IL-6 in rat IEC-6 cells. Non
      proteolytic detachment of the IEC-6 cells also induced elevated levels of IL-6
      mRNA, suggesting that the effect was not caused by a specific protease or
      degradation product, but probably by an effect on cell shape or cell detachment.
      Similar results were seen with the IEC-18 cell line. Trypsin treatment of the IEC
      6 cells also enhanced unstimulated and IL-1 beta costimulated IL-6 secretion, but
      not MCP-1 secretion or mRNA levels. Finally, nuclear levels of the CCAAT/enhancer
      binding protein-beta (C/EBP-beta) were rapidly enhanced after proteolytic
      detachment of the IEC-6 cells, suggesting a mechanism for the enhancement of IL-6
      mRNA responses. These data indicate that epithelial cells can respond to
      proteolytic attack or cell detachment by producing IL-6, a cytokine with several
      anti-inflammatory and antiprotease effects, which may be important in moderating
      the loss of the epithelial layer by its effects on nearby epithelial or
      inflammatory cells.

PMID- 11849321
TI  - Rapid changes in the lymphopoietic and granulopoietic compartments of the marrow
      caused by stress levels of corticosterone.
AB  - Exposure to concentrations of glucocorticoids analogous to those produced during
      stress, trauma and malnutrition had rapid but varying effects on the major
      classes of cells within the marrow. Corticosterone (CS) was given as a subdermal
      implant in young mice and generated 60-95 microg CS/dl of blood compared to 5-15
      microg CS/dl for sham controls over a period of 36 hr. Within 24 hr CS had caused
      losses of 30-70% among the early pro-B, pre-B and immature B cells. The pre-B
      cells were virtually eliminated by 36 hr and the capacity of surviving pro- and
      pre-B cells to cycle was reduced by 70-80%. Interestingly, the earliest of B
      cells, the prepro-B cells, showed considerable resistance to CS, being reduced by
      only 20% at 36 hr. Thus, the pattern of survival within the B-cell compartment
      paralleled the expression of Bcl-2. At the 36-hr time-point there were no changes
      in the proportion of progenitor cells, erythroid or monocytic cells, or number of
      nucleated cells in the marrow. By contrast, 36 hr after exposure to CS there was
      an increase of 30% in the proportion and absolute number of cells in the
      granulocytic compartment. Chronic production of CS appears to reprogramme
      lymphopoiesis and myelopoiesis, perhaps to preserve the first line of immune
      defence at the expense of the lymphoid branch. Resistance to apoptosis and
      modifications in the activity of the glucocorticoid receptor and cytokines
      produced by stromal cells are postulated as targets for CS-driven changes.

PMID- 11849322
TI  - The impact of genomics and related technologies on the search for new
      antibiotics.

PMID- 11849323
TI  - Bradyrhizobium sp. nodulating the Mediterranean shrub Spanish broom (Spartium
      junceum L.).
AB  - AIMS: The molecular diversity of 25 strains of rhizobia, isolated in Sicily from
      root nodules of the Mediterranean shrubby legume Spanish broom (Spartium junceum
      L.), is presented in relation to the known rhizobial reference strains. METHODS
      AND RESULTS: Our approach to the study of the S. junceum rhizobial diversity
      combined the information given by the 16S and the intergenic spacer (IGS) 16S-23S
      rDNA polymorphic region by obtaining them in a single polymerase chain reaction
      (PCR) step. The PCR fragment size of the S. junceum isolates was 2400-2500 bp and
      that of the reference strains varied from 2400 in Bradyrhizobium strains to 2800
      in Sinorhizobium strains. Inter- and intrageneric length variability was found
      among the reference strains. Restriction fragment length polymorphisms (RFLP)
      analysis allowed us to identify eight genotypes among the S. junceum rhizobia
      that were clustered into two groups, both related to the Bradyrhizobium lineage.
      Sequencing of representative strains of the two clusters confirmed these data.
      The 16S-IGS PCR-RFLP approach, when applied to rhizobial reference strains,
      allowed very close species (i.e. Rhizobium leguminosarum/R. tropici) to be
      separated with any of the three enzymes used; however, cluster analysis revealed
      inconsistencies with the 16S-based phylogenesis of rhizobia. CONCLUSIONS:
      Rhizobia nodulating S. junceum in the Mediterranean region belong to the
      Bradyrhizobium lineage. Our results confirm the resolution power of the 16S-23S
      rDNA in distinguishing among rhizobia genera and species, as well as the
      usefulness of the PCR-RFLP method applied to the entire 16S-IGS region for a
      rapid tracking of the known relatives of new isolates. SIGNIFICANCE AND IMPACT OF
      THE STUDY: The present paper is, to our knowledge, the first report on rhizobia
      nodulating a Mediterranean wild woody legume.

PMID- 11849324
TI  - Mechanisms for enhanced biodegradation of petroleum hydrocarbons by a microbe
      colonized gas-liquid foam.
AB  - AIMS: A microbe-colonized gas-liquid foam formulation has been previously shown
      to provide enhanced biodegradation capabilities in soil microcosms. The present
      study considers the reservoir properties of this foam and how this affects
      hydrocarbon degradation rates. METHODS AND RESULTS: Oxygen solubility in protein
      hydrolysate solutions draining from aerated and oxygenated foams was measured.
      The suitability of oxygenated foam to enhance the degradation of n-hexadecane in
      soil microcosms was assessed. Sorption of bacterial isolates at the gas-liquid
      interface was also investigated using a range of microscopy techniques.
      CONCLUSIONS: Oxygenated bioactive foam enhanced biodegradation rates by improving
      oxygen availability and transfer. Biodegradation of n-hexadecane was also
      stimulated by the protein hydrolysate used and by the inclusion of known
      bacterial hydrocarbon-degrading bacteria. The interaction of bacteria with the
      gas-liquid interface was shown to be a significant factor governing the drainage
      of the bacteria from the bioactive foam. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Protein hydrolysate-based bioactive foam may be a suitable treatment technology
      to enhance the biodegradation of petroleum hydrocarbons in soil.

PMID- 11849325
TI  - Aerobic and facultatively anaerobic cellulolytic bacteria from the gut of the
      termite Zootermopsis angusticollis.
AB  - AIMS: To demonstrate the occurrence of cellulolytic bacteria in the termite
      Zootermopsis angusticollis. METHODS AND RESULTS: Applying aerobic cultivation
      conditions we isolated 119 cellulolytic strains from the gut of Z. angusticollis,
      which were assigned to 23 groups of aerobic, facultatively anaerobic or
      microaerophilic cellulolytic bacteria. 16S rDNA restriction fragment pattern and
      partial 16S rDNA sequence analysis, as well as numerical taxonomy, were used for
      the assignment of the isolates. The Gram-positive bacteria of the actinomycetes
      branch could be assigned to the order Actinomycetales including the genera
      Cellulomonas/Oerskovia, Microbacterium and Kocuria. The Gram-positive bacteria
      from the order Bacillales belonged to the genera Bacillus, Brevibacillus and
      Paenibacillus. Isolates related to the genera Afipia, Agrobacterium/Rhizobium,
      Brucella/Ochrobactrum, Pseudomonas and Sphingomonas/Zymomonas from the alpha
      proteobacteria and Spirosoma-like from the "Flexibacteriaceae" represented the
      Gram-negative bacteria. CONCLUSIONS: A cell titre of up to 10(7) cellulolytic
      bacteria per ml, determined for some isolates, indicated that they may play a
      role in cellulose digestion in the termite gut in addition to the cellulolytic
      flagellates and termite's own cellulases. SIGNIFICANCE AND IMPACT OF THE STUDY:
      The impact of bacteria on cellulose degradation in the termite gut has always
      been a matter of debate. In the present survey we investigated the aerobic and
      facultatively anaerobic cellulolytic bacteria in the termite gut.

PMID- 11849326
TI  - Enhancement of bile tolerance in lactococci by Tween 80.
AB  - AIMS: The aim of this study is to clarify the effect of Tween 80 on bile
      tolerance of lactococci. METHODS AND RESULTS: Four out of the six strains of
      lactococci could grow in broth containing 0.3% bile in the presence of 1% Tween
      80, but grew slightly or not at all in the absence of Tween 80. Growing with
      Tween 80 altered the fatty acid composition of all three strains tested, but it
      is not clear which fatty acid influences bile tolerance. Material that absorbed
      light at 260 nm leaked from the cells tested with bile, but the leakage was
      decreased by addition of 1% Tween 80. Coincidentally, the decrease in the cell
      count by exposure to bile was suppressed by addition of Tween 80. CONCLUSIONS:
      Tween 80 enhances bile tolerance of some strains of lactococci. SIGNIFICANCE AND
      IMPACT OF THE STUDY: It is clarified that Tween 80 in the broth contributes to
      the bile tolerance of lactococci by reducing the cellular leakage caused by bile.

PMID- 11849327
TI  - Validation of a polymerase chain reaction/restriction enzyme analysis method for
      species identification of thermophilic campylobacters isolated from domestic and
      wild animals.
AB  - AIMS: To compare and evaluate a polymerase chain reaction/restriction enzyme
      analysis (PCR/REA) method with standard phenotypic tests for the identification
      and differentiation of the thermophilic campylobacters Campylobacter jejuni, C.
      coli, C. lari and C. upsaliensis. METHODS AND RESULTS: One hundred and eighty-two
      presumptive thermophilic campylobacters from 12 different animal species were
      tested by a recently published PCR/REA and standard phenotypic tests. By PCR/REA,
      95% of the isolates were clearly identified as either one of the four
      thermophilic Campylobacter species or as not belonging to this group of organisms
      at all. By standard phenotyping, 174 of the 182 isolates were initially
      identified as either C. jejuni, C. coli, C. lari or C. upsaliensis. Additional
      genotypic tests and phenotyping showed that 52 of these identifications were
      either incorrect or unreliable. Of the C. jejuni isolates, 19% were identified as
      C. coli by initial phenotyping and 27 sheep isolates phenotyped as C. coli or C.
      lari were, in fact, arcobacters. CONCLUSIONS: The PCR/REA was more reliable than
      standard phenotyping for the identification of thermophilic campylobacters from
      different animals. SIGNIFICANCE AND IMPACT OF THE STUDY: Routinely used
      phenotypic tests often resulted in unreliable identifications, requiring
      additional testing. The PCR/REA, however, gave unequivocal results and was
      considered useful for the routine identification of thermophilic campylobacters
      from different animals.

PMID- 11849328
TI  - Genetic diversity of lactococci and enterococci isolated from home-made Pecorino
      Sardo ewes' milk cheese.
AB  - AIMS: To assess the intraspecific genetic diversity of lactococci and enterococci
      isolated from 24-h, 1- and 2-month-old home-made Pecorino Sardo ewes' milk
      cheese. METHODS AND RESULTS: Two molecular techniques, plasmid profiling and
      pulsed-field gel electrophoresis, were used in order to type the isolates at
      strain level. The present study revealed that the lactococcal and enterococcal
      microbial populations of home-made Pecorino Sardo cheese were complex, not only
      24 h after manufacture, but also after 1 and 2 months of ripening. The genetic
      diversity at subspecies level ranged from 58 to 80% during the three periods
      examined. The study also showed that the strains that dominated in the first
      stage of ripening were not necessarily predominant in the later periods. A high
      number of strains isolated at 24 h were still present in the mature cheese, but
      many of the genotypes were only found in the cheese after 1 or 2 months.
      CONCLUSIONS: The results showed a high intraspecific genetic diversity in the
      natural microbial population colonizing home-made Pecorino Sardo cheese. Two
      molecular techniques are necessary for a thorough and precise typing at strain
      level in order to better distinguish between closely related isolates and between
      isolates that probably belong to the same clonal lineage. SIGNIFICANCE AND IMPACT
      OF THE STUDY: The genetic complexity observed in the present study is of
      particular relevance in the preservation of the natural microflora of traditional
      Protected Designation of Origin raw milk cheeses, as well as in the selection of
      new starter strains for the dairy industry.

PMID- 11849329
TI  - Characterization of an antibacterial peptide produced by Brevibacterium linens.
AB  - AIMS: The aim of this research was to investigate the antimicrobial activity
      produced by Brevibacterium linens ATCC 9175. METHODS AND RESULTS: A bacteriocin
      produced by the red smear cheese bacterium B. linens ATCC 9175 was identified.
      The antimicrobial activity was first produced at the exponential growth phase. A
      crude bacteriocin obtained from the culture supernatant fluid was inhibitory to
      some indicator strains. It inhibited the growth of Listeria monocytogenes ATCC
      7644, B. linens ATCC 9172 and Corynebacterium fimi NCTC 7547, but was inactive
      against the Gram-negative bacteria and yeast tested. The bacteriocin was stable
      at 30 degrees C but the activity was lost when the temperature reached 50 degrees
      C. It was sensitive to the proteolytic action of trypsin, papain and pronase E
      and was active between pH 6.0 and 9.0. The bacteriocin was bactericidal to L.
      monocytogenes at 40 AU ml(-1). Bacteriostasis was observed for a low dose of
      bacteriocin (20 AU ml(-1)). CONCLUSIONS: An antibacterial peptide produced by B.
      linens was characterized, presenting potential for use as a biopreservative in
      food systems. SIGNIFICANCE AND IMPACT OF THE STUDY: The identification of a novel
      bacteriocin active against L. monocytogenes addresses an important aspect of food
      protection against pathogens and spoilage micro-organisms.

PMID- 11849330
TI  - Survival of Listeria monocytogenes in commercial food-processing equipment
      cleaning solutions and subsequent sensitivity to sanitizers and heat.
AB  - AIMS: To determine the ability of Listeria monocytogenes to survive exposure to
      commercial food-processing equipment cleaning solutions and subsequent treatment
      with sanitizers or heat. METHODS AND RESULTS: Cells of five strains of L.
      monocytogenes were suspended in 1% solutions of eight commercial cleaners (pH 7.1
      12.5) or in water (control) and incubated at 4 degrees C for 30 min or 48 h
      before populations were determined by plating on tryptose phosphate agar. After
      exposure of cells to cleaning solutions for 30 min, populations of the most
      resistant strain of L. monocytogenes were reduced by < or = 1.63 log10 cfu ml(
      1). In only three highly alkaline cleaning solutions (pH 11.6-12.4) were
      populations reduced significantly (P < or = 0.05) compared with reductions in
      water. After 48 h, populations were significantly higher in one cleaning solution
      (pH 10.4) than in water, while populations in six of the other seven cleaning
      solutions were reduced by > or = 4.72 log10 cfu ml(-1). Cells exposed to cleaning
      solutions for 30 min became sensitive to 4.0 or 6.0 mg l(-1) free chlorine and to
      50 or 100 mg l(-1) benzalkonium chloride and cetylpyridinium chloride, common
      components of quaternary ammonium sanitizers. Cells exposed to four of the five
      test cleaners had D56 degrees C values less than or equal to those of the control
      cells. CONCLUSIONS: Listeria monocytogenes tolerates exposure to a high
      concentration of alkaline cleaning solutions but consequently becomes sensitized
      to sanitizers. SIGNIFICANCE AND IMPACT OF THE STUDY: The elimination of L.
      monocytogenes surviving exposure to alkaline cleaning solutions widely used for
      food-processing equipment is essential and the appropriate use of sanitizers for
      subsequent application to equipment is important in achieving this goal.

PMID- 11849331
TI  - Adaptation of a neutrophilic dairy-associated Bacillus cereus isolate to alkaline
      pH.
AB  - AIMS: This study identified and studied the response of five Bacillus strains,
      isolated from alkaline cleaning in place (CIP) solutions, to alkaline conditions.
      METHODS AND RESULTS: Isolates were identified as B. cereus by 16S rDNA
      sequencing. External and internal cell pH and buffering capacity data of a
      representative strain, Bacillus DL5, were compared to B. cereus ATCC 10702.
      Results indicated that a buffering system was induced when the pH of the growth
      medium increased to above pH 10, which was effective up to pH 12 and presumably
      cell wall associated. Volume measurements and confocal scanning laser microscope
      images of Bacillus DL5 cells showed that cells exhibited more pronounced stress
      symptoms when exposed to pH 10 than at pHs above 10. Long-term exposure of
      Bacillus DL5 to pH 10 or 10.5 indicated that cells grew in planktonic form and
      formed biofilms at both pHs. CONCLUSIONS: Bacillus DL5 was a neutrophile with a
      growth pH range similar to B. cereus ATCC 10702, but tolerated alkaline pH. This
      may be a general trait of the B. cereus species rather than a specific phenomenon
      of isolates from alkaline ecosystems. SIGNIFICANCE AND IMPACT OF THE STUDY: Other
      neutrophilic B. cereus isolates may exhibit similar responses to alkaline
      conditions as the isolates studied here. These results may have important
      implications for dairy manufacturers.

PMID- 11849333
TI  - Evaluation of ribosomal RNA gene restriction patterns for the classification of
      Bacillus species and related genera.
AB  - AIMS: To identify Bacillus species and related genera by fingerprinting based on
      ribosomal RNA gene restriction patterns; to compare ribosomal RNA gene
      restriction patterns-based phylogenetic trees with trees based on 16S rRNA gene
      sequences; to evaluate the usefulness of ribosomal RNA gene restriction patterns
      as a taxonomic tool for the classification of Bacillus species and related
      genera. METHODS AND RESULTS: Seventy-eight bacterial species which include 42
      Bacillus species, 31 species from five newly created Bacillus-related genera, and
      five species from five phenotypically related genera were tested. A total of 77
      distinct 16S rRNA gene hybridization banding patterns were obtained. The
      dendrogram resulting from UPGMA analysis showed three distinct main genetic
      clusters at the 75% banding pattern similarity. A total of 77 distinct 23S and 5S
      rRNA genes hybridization banding patterns were obtained, and the dendrogram
      showed four distinct genetic clusters at the 75% banding pattern similarity. A
      third dendrogram was constructed using a combination of the data from the 16S
      rRNA gene fingerprinting and the 23S and 5S rRNA genes fingerprinting. It
      revealed three distinct main phylogenetic clusters at the 75% banding pattern
      similarity. CONCLUSIONS: The Bacillus species along with the species from related
      genera were identified successfully and differentiated by ribosomal RNA gene
      restriction patterns, and most were distributed with no apparent order in various
      clusters on each of the three dendrograms. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Our data indicate that ribosomal RNA gene restriction patterns can be used to
      reconstruct the phylogeny of the Bacillus species and derived-genera that
      approximates, but does not duplicate, phylogenies based on 16S rRNA gene
      sequences.

PMID- 11849332
TI  - Evaluation of the international phage typing set and some experimental phages for
      typing of Listeria monocytogenes from poultry in Spain.
AB  - AIMS: The validity of the international phage set and 13 experimental phages for
      subtyping Listeria monocytogenes strains isolated from poultry in Spain was
      investigated. METHODS AND RESULTS: Ninety-six L. monocytogenes strains (52 from
      serogroup 1/2 and 44 from serogroup 4) were phage-typed using the international
      phage set, 10 experimental phages for typing serogroup 1/2 strains (seven
      isolated in France: 1313, 9425, 1807, 351, 881, 717 and 586-, and three from
      Denmark: 5775, 12682 and 6223-) and three experimental phages isolated in France
      for typing serogroup 4 strains (2425 A, 4286 and 197). Percentages of serogroup
      1/2, serogroup 4 and total phage-typeable strains were 57.7%, 52.3% and 55.2%,
      respectively. Important differences in the behaviour of the phages tested were
      found. The typeability rate, the specificity index and the percentage of strong
      reactions were greater in the phages of international set than in the
      experimental phages. The number of phage typeable strains and the number of phage
      types (42) were not modified by the use of experimental phages. CONCLUSIONS: The
      phage set used was not effective for typing L. monocytogenes strains from poultry
      in Spain, because a low typeability rate was found. SIGNIFICANCE AND IMPACT OF
      THE STUDY: Our results suggest the importance of the availability of new phages
      specific to a geographical area in order to improve the typeability of the
      system.

PMID- 11849334
TI  - Comparison of molecular and antibiotic resistance profile methods for the
      population analysis of Bradyrhizobium spp. (TGx) isolates that nodulate the new
      TGx soybean cultivars in Africa.
AB  - AIMS: Comparison of molecular and antibiotic resistance profile methods to
      identify an easy method that can differentiate between strains of introduced
      Bradyrhizobium japonicum and the indigenous Bradyrhizobium spp. (TGx) isolates
      which nodulate the newly developed TGx soybean cultivars in Africa. METHODS AND
      RESULTS: Restriction fragment length polymorphism (RFLP) of 16S rDNA generated by
      five restriction enzymes, banding patterns in Southern hybridization using nod
      and nif genes as probes, and resistance patterns of the isolates to nine
      antibiotics, were used to group 26 Bradyrhizobium spp. (TGx) isolates and four
      other Bradyrhizobium strains. The clusters of isolates obtained from the four
      grouping methods were all different, although all methods revealed large genetic
      diversity among the isolates. CONCLUSIONS: Results indicate that the antibiotic
      resistance profile method is as good as the three molecular methods used in this
      study for phylogenetic grouping of the Bradyrhizobium spp. (TGx) isolates, which
      may serve as a basis for further characterization of selected isolates from each
      group. SIGNIFICANCE AND IMPACT OF THE STUDY: The antibiotic resistance profile
      method can be used as a simple means of assessing genetic variability and
      grouping of a large number of Bradyrhizobium spp. (TGx) isolates. Representative
      isolates from each group can then be selected for further characterization.

PMID- 11849335
TI  - Detection of root mat associated Agrobacterium strains from plant material and
      other sample types by post-enrichment TaqMan PCR.
AB  - AIMS: The development of a fluorogenic, 5' nuclease, TaqMan PCR assay for the
      detection of Ri-plasmids from root mat inducing Agrobacterium biovar 1 strains.
      METHODS AND RESULTS: A TaqMan probe and primer set were designed within the T-DNA
      sequence of a known root mat inducing Agrobacterium strain. One hundred and ten
      Agrobacterium and closely related bacteria were tested using this novel PCR and
      compared with results from a conventional PCR which detects Ti and Ri-plasmids.
      The Agrobacterium selective media, Medium 1A was modified into broth form for use
      as an enrichment of the pathogen from samples prior to the TaqMan PCR.
      CONCLUSIONS: The root mat pathogen was detected successfully from a range of
      sample types using the enriched fluorogenic PCR assay, negating the need for
      complex DNA extraction procedures and post-PCR processing techniques such as gel
      electrophoresis. The technique is therefore a rapid and cost-effective detection
      method. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first known report of a
      fluorogenic, 5' nuclease, TaqMan assay designed to detect an Agrobacterium plant
      pathogen. The method can be used as a model system for the detection of other
      Agrobacterium pathogens.

PMID- 11849336
TI  - Successive rapid reductive dehalogenation and mineralization of pentachlorophenol
      by the indigenous microflora of farmyard manure compost.
AB  - AIMS: To determine whether composting with animal manure can be used to
      effectively remediate soil from a pentachlorophenol (PCP)-contaminated site, and
      to establish the fate of the degraded xenobiotic. METHODS AND RESULTS:
      Contaminated soil from a sawmill site was mixed with farm animal manure and
      composted in a 0.5 m3 silo under fully aerobic conditions. The disappearance and
      fate of PCP was monitored by gas chromatography (GC-ECD) and extensive
      mineralization confirmed in experiments with 14C-radiolabelled PCP. The
      disappearance of PCP was rapid and virtually complete within 6 days, prior to the
      onset of thermophilic conditions. Dechlorination of the PCP was found to be both
      reductive and sequential. CONCLUSIONS: PCP removal from contaminated soil by
      aerobic composting with animal manure is efficient and proceeds via reductive
      dechlorination to virtually complete mineralization. This contrasts with other
      chlorophenol composting regimes in which mineralization is achieved but
      dechlorination intermediates do not accumulate to detectable levels. SIGNIFICANCE
      AND IMPACT OF THE STUDY: The results of this study demonstrate that anaerobic
      reductive dechlorination can proceed in an aerobic composting environment and
      contribute to efficient pentachlorophenol removal. Farmyard manure composts may
      represent a rapid, low-cost, low-technology option for treatment of chlorophenol
      contaminated soils.

PMID- 11849337
TI  - mlpB, a gene encoding a new lipoprotein in Myxococcus xanthus.
AB  - AIMS: To search for and study the genes involved in the regulation of phosphate
      in the soil developmental bacterium Myxococcus xanthus. METHODS AND RESULTS: The
      mlpB gene encoding a 149 residue polypeptide was identified while screening for
      genes with products related to phosphate metabolism. The amino terminal 19
      residues of MlpB encode a typical prokaryotic signal sequence with a putative
      lipoprotein cleavage site. CONCLUSIONS: In this study, a new myxobacterial
      putative lipoprotein is reported. The data suggest that MlpB may be involved in
      the secretion of phosphate-related proteins. SIGNIFICANCE AND IMPACT OF THE
      STUDY: Soil bacteria have complex regulatory systems for using inorganic
      phosphate. This nutrient is limiting in the environment, and has a critical
      importance for growth and in the initiation of differentiation for developmental
      bacteria. A number of proteins are involved in all these processes, including
      membrane lipoproteins, which are being increasingly studied in M. xanthus.

PMID- 11849338
TI  - Assessment of the fructanolytic activities in the rumen bacterium Treponema
      saccharophilum strain S.
AB  - AIMS: To characterize the fructose polymer degrading enzymes of rumen bacterium
      Treponema saccharophilum strain S. METHODS AND RESULTS: Conventional methods were
      used to examine bacterial growth and enzyme activities. Electrophoretic zymogram
      under native conditions, and thin layer chromatography, were applied to identify
      and characterize the enzymes. Treponema saccharophilum utilized Timothy grass
      fructan, inulin and sucrose but not free fructose. Timothy grass fructan was
      degraded at a significantly higher rate than sucrose and inulin. Two
      fructanolytic enzymes were found in the soluble, and one in the membrane fraction
      of bacterial cell extract. The first degraded each mentioned carbohydrate to
      monosaccharides. The second released oligosaccharides only from Timothy grass
      fructan. CONCLUSIONS: The bacterium T. saccharophilum strain S is capable of
      synthesizing non-specific beta-fructofuranosidases and 2,6-beta-D-fructan
      fructanohydrolase. The enzymes are of constitutive character. SIGNIFICANCE AND
      IMPACT OF THE STUDY: It has been stated for the first time that the 2,6-beta-D
      fructan fructanohydrolase is synthesized by the rumen bacterium T.
      saccharophilum. This organism appears to be responsible for grass fructan
      degradation in the rumen.

PMID- 11849339
TI  - Microbial analysis of Malaysian tempeh, and characterization of two bacteriocins
      produced by isolates of Enterococcus faecium.
AB  - AIMS: Isolation of bacteriocinogenic lactic acid bacteria (LAB) from the
      Malaysian mould-fermented product tempeh and characterization of the produced
      bacteriocin(s). METHODS AND RESULTS: LAB were present in high numbers in final
      products as well as during processing. Isolates, Enterococcus faecium B1 and E.
      faecium B2 (E. faecium LMG 19827 and E. faecium LMG 19828, respectively)
      inhibited Gram-positive indicators, including Listeria monocytogenes. Partially
      purified bacteriocins showed a proteinaceous nature. Activity was stable after
      heat-treatment except at alkaline pH values. Both strains displayed a
      bacteriostatic mode of action. Bacteriocin production was associated with late
      exponential/early stationary growth. Molecular mass, calculated by SDS-PAGE, was
      3.4 kDa for B1 bacteriocin, and 3.4 kDa and 5.8 kDa for B2 bacteriocins. PCR
      screening of enterocin-coding genes revealed three amplified fragments in total
      genomic DNA that may correspond with PCR signals for enterocin P, enterocin L50A
      and enterocin L50B. Both B1 and B2 contained a 42-kb plasmid. No differences in
      bacteriocinogenic capacity were found between wild type strains and plasmid-cured
      strains. CONCLUSIONS: It was possible to isolate bacteriocinogenic E. faecium
      active against various Gram-positive bacteria from final products of tempeh.
      SIGNIFICANCE AND IMPACT OF THE STUDY: A first step in applying biopreservation to
      fermented South-east Asian foods is to obtain bacteriocinogenic LAB from this
      source. Such isolates may also be used for biopreservation of mould-fermented
      foods in general, including various types of mould-ripened cheese.

PMID- 11849340
TI  - Monitoring of Staphylococcus xylosus DSM 20266 added as starter during
      fermentation and ripening of soppressata molisana, a typical Italian sausage.
AB  - AIMS: "Soppressata molisana", a fermented sausage produced in southern Italy, is
      commonly obtained without starter addition. However, the use of starter cultures
      is more and more recommended in meat fermentation processes in order to guarantee
      stable production performance. In this study, the survival of the Staphylococcus
      xylosus DSM 20266 was evaluated during the ripening of "soppressata molisana"
      fermented sausage. METHODS AND RESULTS: The fastest method of RAPD-PCR was
      employed for discrimination of the added strain from those naturally present
      during the ripening of the "soppressata molisana". The results obtained were
      confirmed by analysis of the DNA macrorestriction profile by PFGE. The
      electrophoretic pattern of bacterial total proteins was also studied, but clear
      differences between the different strains could not be detected. CONCLUSIONS: The
      RAPD technique was a valid tool for monitoring Staph. xylosus DSM 20266 in
      "sopressata molisana". SIGNIFICANCE AND IMPACT OF THE STUDY: This study
      highlights the possibility of monitoring the presence of Staph. xylosus strains
      during the ripening of fermented sausages by a reliable and repeatable technique
      such as RAPD.

PMID- 11849341
TI  - Early detection of spoilage moulds in bread using volatile production patterns
      and quantitative enzyme assays.
AB  - AIMS: Early detection of spoilage fungi (two Eurotium spp., a Penicillium
      chrysogenum species) in bread analogues over periods of 72 h at 25 degrees C and
      0.95 water activity was evaluated using volatile production patterns, hydrolytic
      enzyme production, and changes in fungal populations. METHODS AND RESULTS: Using
      an electronic nose system it was possible to differentiate between uninoculated
      controls and samples contaminated with P. chrysogenum within 28 h. After 40-48 h
      it was possible to differentiate between the Eurotium spp., P. chrysogenum and
      the control using Principal Component Analysis (PCA). Cluster analyses could
      differentiate between the control, P. chrysogenum and the Eurotium spp. after 40
      h. Of seven hydrolytic enzymes examined after 48 h, the specific activities of
      three were significantly different from uninoculated control bread. There were
      also differences between the mould species in production of three enzymes.
      Penicillium chrysogenum populations increased fastest, from about 10(3) cfu g(-1)
      to 10(6)-10(7) cfu g(-1) after 72 h. For the Eurotium spp. this increase was
      slower. CONCLUSIONS: Overall, this study suggests, for the first time, that an
      electronic nose system using a surface polymer sensor array is able to detect
      qualitative changes in volatile production patterns for the early detection of
      the activity of spoilage moulds in bakery products. SIGNIFICANCE AND IMPACT OF
      THE STUDY: Potential exists for application of such systems for microbial quality
      assurance in intermediate moisture food products.

PMID- 11849342
TI  - Isolation and characterization of Lactococcus piscium strains from vacuum
      packaged refrigerated beef.
AB  - AIMS: To characterize gram-positive, catalase-negative, psychrotrophic, lactic
      acid-homofermentative, non-motile cocci isolated from vacuum-packaged
      refrigerated beef using phenotypic and genotypic methods. METHODS AND RESULTS: A
      total of 89 strains was isolated at 2 and 6 weeks as one of the predominant
      microflora of five samples of vacuum-packaged beef stored at 2 degrees C. The
      strains were compared with reference strains of some gram-positive, catalase
      negative cocci using SDS-PAGE whole-cell protein pattern analysis, biochemical
      characterization and 16S rDNA sequencing. The biochemical and physiological
      characteristics of the isolates resembled those of Lactococcus piscium GTC
      552(T). Numerical analysis of the SDS-PAGE whole-cell protein patterns resulted
      in close clustering of the strains with L. piscium GTC 552(T) (r > 0.68). Other
      Lactococcus and Leuconostoc species could be distinguished from the isolates
      using SDS-PAGE whole-cell protein patterns (r < 0.58) and biochemical
      characteristics. The 16S rDNA sequencing of four randomly selected strains showed
      that the strains differed from L. piscium GTC 552(T) by two to three bases in the
      highly variable region of the sequence. This is the first report on the isolation
      of L. piscium from vacuum-packaged beef. CONCLUSIONS: The gram-positive catalase
      negative cocci isolated from vacuum-packaged refrigerated beef have been
      identified as L. piscium. SIGNIFICANCE AND IMPACT OF THE STUDY: The findings of
      this work contribute to the knowledge of the microflora of vacuum-packaged
      refrigerated beef.

PMID- 11849343
TI  - Identification of Salmonella enteritidis outer membrane proteins expressed during
      attachment to human intestinal epithelial cells.
AB  - AIMS: To express and identify the Salmonella enterica ser. Enteritidis outer
      membrane proteins that are involved in the attachment to human intestinal
      epithelial cells. METHODS AND RESULTS: Salmonella Enteritidis attachment proteins
      were expressed by infection of human intestinal epithelial cells (int-407) with
      Salm. Enteritidis strain SE28, followed by pulse labelling with [35S]-methionine.
      Outer membrane proteins were separated by TritonX-114 phase partitioning, and
      were detected by Salm. Enteritidis-specific polyclonal antibody. Outer membrane
      proteins of molecular weights 82.3, 75.6, 49.3, 35.5 and 19.3 kDa were newly
      synthesized. Expression of 31.2 and 16 kDa proteins was up-regulated, whereas the
      expression of 40.7 kDa protein was down-regulated. Polyclonal antibodies against
      the 82.3 and 75.6 kDa proteins significantly (P < 0.05) reduced the binding of
      Salm. Enteritidis to int-407 cells in vitro. CONCLUSIONS: Outer membrane proteins
      82.3 and 75.6 kDa are potentially involved in the attachment of Salm. Enteritidis
      to the intestinal mucosa. SIGNIFICANCE AND IMPACT OF THE STUDY: Outer membrane
      proteins 82.3 and 75.6 kDa identified in this study could be used as potential
      vaccines to block or reduce Salm. Enteritidis colonization in chickens.

PMID- 11849345
TI  - Strategies for the transformation of filamentous fungi.

PMID- 11849346
TI  - Salmonella enterica serotype Enteritidis phage types 4, 7, 6, 8, 13a, 29 and 34:
      a comparative analysis of genomic fingerprints from geographically distant
      isolates.
AB  - AIMS: To evaluate genetic heterogeneity in the most common phage types of
      Salmonella enterica serovar Enteritidis. METHODS AND RESULTS: A total of 233
      isolates of Salm. Enteritidis from England, Northern Ireland, Spain, Hong Kong
      and the USA belonging to phage types (PT) 4 (n=88), PT7 (n=12), PT6 (n=72), PT8
      (n=14), PT13a (n=29), PT29 (n=14) and PT34 (n=4) were characterized by PstI-SphI
      (PS) ribotyping and pulsed-field gel electrophoresis after digestion of DNA with
      XbaI. PS ribotyping differentiated the isolates into 53 different PS types and
      PFGE showed 14 different macrorestriction profiles; with the combination of both
      methods, 73 combined types were identified. Some of these clones appeared to be
      present within several countries. Movement of foodstuffs, animals or people may
      have been involved in the spread of these strains. On the other hand, some clones
      were only found in specific locations. CONCLUSIONS: Several well defined clonal
      lines seem to co-exist within the different phage types included in this study,
      and a combined typing approach may constitute a useful tool for epidemiological
      investigations. Clustering analysis of ribotypes and PFGE types agree with
      previous studies and suggest that phage types that share receptor binding
      properties can be distinguished as two families: the PT4 family including PT7 and
      PT6, and the PT8 family including PT13a. The other phage types are difficult to
      place in a family unless the geographical site of isolation is known.
      SIGNIFICANCE AND IMPACT OF THE STUDY: This paper reports on an extensive
      assessment of the use of molecular tools for the study of the epidemiology of the
      enteric pathogen Salm. Enteritidis. It also gives new information regarding
      relationships among some common phage types.

PMID- 11849347
TI  - The effect of a sewage treatment plant effluent on the faecal coliforms and
      enterococci populations of the reception river waters.
AB  - AIMS: A rural sewage treatment plant and the effect of its effluent on the
      enterococci and faecal coliforms populations of the receiving river waters was
      evaluated. METHODS AND RESULTS: The enumeration of bacteria was performed by
      membrane filtration. Diversity and population similarity were analysed using the
      PhP-plates system. The treatment plant reduces the number of enterococci and
      faecal coliforms to values similar to those observed upstream. All water samples
      showed a high diversity for both bacterial populations. A high similarity in the
      composition and structure, was detected among all the samples. CONCLUSIONS: The
      impact of the disposal of treated sewage on the river did not modify the
      composition of either bacterial populations in the river water. SIGNIFICANCE AND
      IMPACT OF THE STUDY: The biochemical phenotyping of bacterial populations is a
      reliable tool for ecological and biodiversity studies. The obtained results
      provide a better understanding of the sewage treatment process and the impact of
      the treated sewage effluents in the environment.

PMID- 11849348
TI  - The amino acid requirements of Corynebacterium diphtheriae PW 8 substrain CN
      2000.
AB  - AIMS: To determine the amino acid requirement and utilization pattern of
      Corynebacterium diphtheriae during growth and toxin production. METHODS AND
      RESULTS: Comparing across different batches of beef-based media, the growth and
      toxin yield were correlated significantly with nine of the amino acids. The amino
      acid utilization pattern during growth of C. diphtheriae further showed that only
      four of the nine amino acids, namely cystine, histidine, aspartate and
      methionine, were critical for growth of the vaccine strain. Further
      investigations using synthetic media with combinations of amino acid supplements
      demonstrated that among the four, cystine was the most growth limiting.
      CONCLUSIONS: Only certain amino acids are critical for growth and toxin
      production by C. diphtheriae, cystine being the single most important.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Owing to the potential threat from Bovine
      Spongiform Encephalopathy (BSE), a need is recognized by vaccine manufacturers to
      substitute beef-based production media. An understanding of the specific amino
      acid requirements would help to develop and optimize alternative production
      media.

PMID- 11849349
TI  - Distribution of virulence genes in Aeromonas spp. isolated from Sardinian waters
      and from patients with diarrhoea.
AB  - AIMS: To characterize 46 isolates of different Aeromonas spp. strains (26
      Aeromonas hydrophila, 13 Aeromonas sobria and 7 Aeromonas salmonicida) isolated
      from coastal water and clinical sources in Sardinia, Italy. METHODS AND RESULTS:
      The isolates were analysed for the production of the following virulence
      properties: slime, haemolysin, gelatinase and protease production, and adhesion
      to eucaryotic epithelial cells. The presence of known virulence genes: A.
      hydrophila cytolytic enterotoxin gene AHCYTOEN; type IV pilus gene Tap; Bundle
      forming pilus genes BfpA and BfpG were investigated using polymerase chain
      reaction (PCR). In addition the enterobacterial repetitive intergenic consensus
      sequences (ERIC)-PCR fingerprinting was used to further differentiate the
      strains. CONCLUSIONS: This study confirms the presence of virulent Aeromonas
      strains in the Mediterranean sea. The study also found a greater prevalence of
      haemolysin, protease and gelatinase production, as well as a higher adhesion
      capacity, among strains isolated from patients with diarrhoea. SIGNIFICANCE AND
      IMPACT OF THE STUDY: This is the first time that Aeromonads have been isolated
      and characterized from Sardinian waters and from patients with diarrhoea in
      Sardinia. This study adds to our knowledge of the ecology of this micro-organism
      and may in the future help prevent infections both in fish and in humans.

PMID- 11849350
TI  - Colonization of the developing rhizosphere of sugar beet seedlings by potential
      biocontrol agents applied as seed treatments.
AB  - AIMS: Poor colonization of the rhizosphere is a major constraint of seed
      treatment biological control. The objectives of this study were to; examine the
      colonization of the rhizosphere of sugar beet seedlings by selected
      rhizobacteria; determine the influence of the host rhizosphere and percolating
      water on the distribution of the bacteria; and deliver two biological control
      agents (BCAs) by co-inoculation. METHODS AND RESULTS: Rifampicin-resistant
      bacterial strains (Rif +) applied as single treatments to seed sown in columns of
      field soil produced persistent populations of 5-9 log10 cfu g-1 in the infection
      court of the damping-off pathogen Aphanomyces cochlioides in a controlled
      environment. However, isolates varied in their ability to colonize the lower
      rhizosphere. Percolating water significantly increased the colonization of the
      upper rhizosphere. Bacterial populations in the soil profiles of "non
      rhizosphere" controls declined markedly with time. There was no interaction
      between the two selected BCAs applied as a seed treatment mixture. CONCLUSIONS:
      The distribution of the bacteria resulted primarily from root colonization
      although percolating water may modify the colonization profiles. Co-inoculation
      of the sugar-beet rhizosphere is a viable proposition. SIGNIFICANCE AND IMPACT OF
      THE STUDY: Potential BCAs were successfully delivered to the known infection
      court of A. cochloides and persisted for the infection period. This bioassay can
      be used as a tool for the selection of BCAs for field trials.

PMID- 11849351
TI  - Use of lacticin 481 to facilitate delivery of the bacteriophage resistance
      plasmid, pCBG104 to cheese starters.
AB  - AIMS: Use of lacticin 481 to facilitate the conjugal transfer of the
      bacteriophage resistance plasmid pCBG104 to various starter cultures. METHODS AND
      RESULTS: A raw milk isolate of Lactococcus was found to harbour determinants for
      lacticin 481 production and immunity and phage resistance on a plasmid designated
      pCBG104. The lacticin 481 was successfully used to mobilize the phage resistance
      determinant to a variety of cheese starters enabling the formation of highly
      phage resistant starters. In addition, it facilitated the stacking of a number of
      phage resistance genes, namely a type I restriction modification system, a phage
      abortive infection system and a phage adsorption blocking system in a single
      Lactococcus strain without the use of recombinant techniques. The transconjugants
      were all shown to produce lacticin 481 and to contain the entire 481 operon.
      Subsequently one transconjugant was selected and successfully used for large
      scale cheddar cheese manufacture. CONCLUSIONS: Lacticin 481 could be used as a
      food-grade selectable marker to facilitate the introduction of advantageous
      traits to starter cultures for industrial food fermentations. SIGNIFICANCE AND
      IMPACT OF THE STUDY: Food-grade selectable markers greatly facilitate the
      introduction of various advantageous traits to starter cultures for industrial
      food fermentation. Indeed self-cloning which is becoming increasingly important
      for strain improvement has a requirement for the identification and demonstration
      of the utility of tools such as lacticin 481.

PMID- 11849352
TI  - Post-harvest biological control by Pantoea agglomerans (CPA-2) on Golden
      Delicious apples.
AB  - AIMS: To investigate the potential of Pantoea agglomerans to control the major
      post-harvest diseases on Golden Delicious apples. METHODS AND RESULTS: In
      laboratory trials, a high level of control of Penicillium expansum, Botrytis
      cinerea and Rhizopus stolonifer was obtained with P. agglomerans. In semi
      commercial trials at 1degrees C in air and a low oxygen atmosphere, the reduction
      of blue mould was 81% and 100%, respectively, and control of grey mould was
      achieved equally with P. agglomerans and imazalil. In trials at 1degrees C and
      seven atmosphere conditions, maximum reduction in decay was 80% obtained at 3% O2
      6% CO2. The population of P. agglomerans on apples followed the same pattern
      under all three atmosphere conditions studied. CONCLUSIONS: Pantoea agglomerans
      could be used effectively on apples under a wide range of temperature and
      atmosphere conditions. SIGNIFICANCE AND IMAPCT OF THE STUDY Pantoea agglomerans
      can be used as a biocontrol agent on apples at 8 x 10(7) cfu ml-1, the same
      concentration as in pears. This will facilitate the application of this
      biological control agent by the growers in packing houses.

PMID- 11849353
TI  - Metabolism of Alcaligenes denitrificans in biofilm vs planktonic cells.
AB  - AIMS: To compare the effect of phosphorous concentration (200 mg P l(-1) and 20
      mg P l(-1)) on the denitrifying efficiency of Alcaligenes denitrificans when in
      the form of planktonic cells or in the form of a biofilm, and to select the most
      adequate C/N ratio. METHODS AND RESULTS: Two types of assays were carried out:
      with planktonic cells and with cells in biofilm form. Anoxic bottles with the
      appropriate C/N and phosphorous concentration were incubated at 30 degrees C and
      submitted to orbital shaking at 150 rev min(-1). The specific activity of cells
      in biofilm form, in terms of substrate consumption, was significantly higher than
      cells in planktonic form. With regard to the effect of increasing phosphorous
      concentration, an increase in specific activity was also only evident when the
      cells were in biofilm form. CONCLUSIONS: The two forms showed different
      performances and phosphorous concentration only markedly affected the biofilm
      form. SIGNIFICANCE AND IMPACT OF THE STUDY: The importance of the C/N/P ratio in
      the denitrification process is demonstrated. As there was no report in the
      literature about the stoichiometric relationship of heterotrophic denitrification
      with citrate, its stoichiometry, including the requirement for cell synthesis,
      was determined.

PMID- 11849355
TI  - Mild heat treatment of lettuce enhances growth of Listeria monocytogenes during
      subsequent storage at 5 degrees C or 15 degrees C.
AB  - AIMS: The objective of this study was to determine the influence of mild heat
      treatment, storage temperature and storage time on the survival and growth of
      Listeria monocytogenes inoculated onto cut iceberg lettuce leaves. METHODS AND
      RESULTS: Before or after inoculation with L. monocytogenes, cut iceberg lettuce
      leaves were dipped in water (20 or 50 degrees C) containing or not 20 mg l(-1)
      chlorine, for 90 s, then stored at 5 degrees C for up to 18 days or 15 degrees C
      for up to 7 days. The presence of 20 mg l(-1) chlorine in the treatment water did
      not significantly (alpha=0.05) affect populations of the pathogen, regardless of
      other test parameters. The population of L. monocytogenes on lettuce treated at
      50 degrees C steadily increased throughout storage at 5 degrees C for up to 18
      days. At day 10 and thereafter, populations were 1.7-2.3 log10 cfu g(-1) higher
      on lettuce treated at 50 degrees C after inoculation compared with untreated
      lettuce or lettuce treated at 20 degrees C, regardless of chlorine treatment. The
      population of L. monocytogenes increased rapidly on lettuce stored at 15 degrees
      C. At 2 and 4 days, significantly higher populations were detected on lettuce
      that had been treated at 50 degrees C, compared with respective samples that had
      been treated at 20 degrees C, regardless of inoculation before or after
      treatment, or the presence of 20 mg l(-1) chlorine in the treatment water.
      CONCLUSIONS: The results clearly demonstrated that mild heat treatment of cut
      lettuce leaves enhances the growth of L. monocytogenes during subsequent storage
      at 5 or 15 degrees C. SIGNIFICANCE AND IMPACT OF THE STUDY: Mild heat treatment
      of cut lettuce may result in a prolonged shelf life as a result of delaying the
      development of brown discoloration. However, heat treatment also facilitates the
      growth of L. monocytogenes during storage at refrigeration temperature, thereby
      increasing the potential risk of causing listeriosis.

PMID- 11849354
TI  - Characterization of a cationic surfactant-resistant mutant isolated spontaneously
      from Escherichia coli.
AB  - AIMS: In order to investigate the mechanism of bacterial resistance to
      surfactants, a spontaneous mutant of Escherichia coli, OW66, resistant to a
      cationic surfactant cetyltrimethylammonium bromide (CTAB), was isolated and its
      physiological properties analysed. METHODS AND RESULTS: Strain OW66 grew in M9
      medium containing CTAB at 45 micromol l(-1), whereas its parent strain, OW6, did
      not, even at 15 micromol l(-1). The mutant was also resistant to some other
      surfactants, antibiotics, heavy metals, organic solvents and oxidants examined.
      To determine the differences in physiology between strains OW66 and OW6, the
      compositions of their cell surface structures were analysed. In strain OW66, the
      relative content of OmpC in particular was higher than that of OmpF, whereas a
      reverse situation was seen in OW6 strain. The lipopolysaccharide (LPS) profile
      was different between these strains, and altered LPS in strain OW66 was suggested
      to be involved in the resistance to CTAB. CONCLUSIONS: A CTAB-resistant E. coli
      isolate possesses an altered outer membrane. SIGNIFICANCE AND IMPACT OF THE
      STUDY: Treatment with a relatively low concentration of CTAB was found to
      introduce multi-drug resistance into bacterial cells. This acquired resistance
      should be taken into account with the frequent use of surfactants in industries
      and various environments.

PMID- 11849356
TI  - Microbial communities in different soil types do not converge after diesel
      contamination.
AB  - AIMS: To study the comparative effect of diesel addition and simulated
      bioremediation on the microbial community in three different soil types. METHODS
      AND RESULTS: Three different soils were amended with diesel and bioremediation
      treatment simulated by addition of nutrients. The progress of bioremediation, and
      the effect on the indigenous microbial communities, was monitored using
      microbiological techniques. These included basal respiration, sole carbon source
      utilization patterns using both a commercially-available substrate set and a set
      designed to highlight changes in hydrocarbon-utilizing bacteria, and phospholipid
      fatty acid (PLFA) profiling. The development of active hydrocarbon-degrading
      communities was indicated by the disappearance of diesel, increases in soil
      respiration and biomass, and large changes in the sole carbon source utilization
      patterns and PLFA profiles compared with control soils. However, comparison of
      the relative community structure of the three soils using PLFA profiling showed
      that there was no tendency for the community structure of the three different
      soil types to converge as a result of contamination. In fact, they became more
      dissimilar as a result. Changes in the sole carbon source utilization patterns
      using the commercially-available set of carbon sources indicated the same result
      as shown by PLFA profiling. The specially selected set of carbon sources yielded
      no additional information compared with the commercially-available set.
      CONCLUSIONS: Diesel contamination does not result in the development of similar
      community profiles in different soil types. SIGNIFICANCE AND IMPACT OF THE STUDY:
      The results suggest that different soils have different inherent microbial
      potential to degrade hydrocarbons, a finding that should be taken into account in
      impact and risk assessments. Following the development of the microbial community
      and its recovery is a useful and sensitive way of monitoring the impact and
      recovery of oil-contaminated soils.

PMID- 11849357
TI  - The cloning and characterization of a second alpha-amylase of A. hydrophila
      JMP636.
AB  - AIMS: The aim of this study was to identify, clone and characterize the second
      amylase of Aeromonas hydrophila JMP636, AmyB, and to compare it to AmyA. METHODS
      AND RESULTS: The amylase activity of A. hydrophila JMP636 is encoded by multiple
      genes. A second genetically distinct amylase gene, amyB, has been cloned and
      expressed from its own promoter in Escherichia coli. AmyB is a large alpha
      amylase of 668 amino acids. Outside the conserved domains of alpha-amylases there
      is limited sequence relationship between the two alpha-amylases of A. hydrophila
      JMP636 AmyA and AmyB. Significant (80%) similarity exists between amyB and an
      alpha-amylase of A. hydrophila strain MCC-1. Differences in either the functional
      properties or activity under different environmental conditions as possible
      explanations for multiple copies of amylases in JMP636 is less likely after an
      examination of several physical properties, with each of the properties being
      very similar for both enzymes (optimal pH and temperature, heat instability).
      However the reaction end products and substrate specificity did vary enough to
      give a possible reason for the two enzymes being present. Both enzymes were
      confirmed to be alpha-type amylases. CONCLUSIONS: AmyB has been isolated,
      characterized and then compared to AmyA. SIGNIFICANCE AND IMPACT OF THE STUDY:
      The amylase phenotype is rarely encoded by more than one enzyme within one
      strain, this study therefore allows the better understanding of the unusual
      amylase production by A. hydrophila.

PMID- 11849358
TI  - Exopolysaccharide production by Streptococcus thermophilus SY: production and
      preliminary characterization of the polymer.
AB  - AIMS: To evaluate the effect of yeast extract (YE) concentration, temperature and
      pH on growth and exopolysaccharide (EPS) production in a whey-based medium by
      Streptococcus thermophilus SY and to characterize the partially purified EPS.
      METHODS AND RESULTS: Factorial experiments and empirical model building were used
      to optimize fermentation conditions and the chemical composition, average
      molecular weight (MW) and rheological properties of aqueous dispersions of the
      EPS were determined. Exopolysaccharide production was growth associated and was
      higher (152 mg l(-1)) at pH 6.4 and 36 degrees C with 4 g l(-1) YE. High
      performance size exclusion chromatography of the partially purified EPS showed
      two peaks, with a weight average MW of 2 x 10(6) and 5 x 10(4), respectively. The
      EPS was a heteropolysaccharide, with a glucose : galactose : rhamnose ratio of 2
      : 4.5 : 1. Its water dispersions had a pseudoplastic behaviour and showed a
      higher viscosity of xanthan solutions. SIGNIFICANCE AND IMPACT OF THE STUDY: The
      fermentation conditions and some properties of an EPS produced by Strep.
      thermophilus, a dairy starter organism, were described.

PMID- 11849359
TI  - Genotypic and phenotypic characterization of garlic-fermenting lactic acid
      bacteria isolated from som-fak, a Thai low-salt fermented fish product.
AB  - AIMS: To evaluate the importance of garlic for fermentation of a Thai fish
      product, and to differentiate among garlic-/inulin-fermenting lactic acid
      bacteria (LAB) at strain level. METHODS AND RESULTS: Som-fak was prepared by
      fermentation of a mixture of fish, salt, rice, sucrose and garlic. pH decreased
      to 4.5 in 2 days, but omitting garlic resulted in a lack of acidification. LAB
      were predominant and approximately one third of 234 isolated strains fermented
      garlic and inulin (the carbohydrate reserve in garlic). These strains were
      identified as Lactobacillus pentosus and Lact. plantarum. Randomly Amplified
      Polymorphic DNA (RAPD) analysis revealed one major RAPD type (29 strains)
      isolated from all stages of fermentation. CONCLUSION: Garlic was essential for
      acidification of som-fak and garlic-fermenting strains constituted a significant,
      homogeneous part of the LAB flora. SIGNIFICANCE AND IMPACT OF THE STUDY: The
      present study indicates the role of fructans (garlic/inulin) as carbohydrate
      sources for LAB. Fructan fermenters may have several biotechnological
      applications, for example, as probiotics.

PMID- 11849360
TI  - Reduction of ferric iron by acidophilic heterotrophic bacteria: evidence for
      constitutive and inducible enzyme systems in Acidiphilium spp.
AB  - AIMS: To compare the abilities of two obligately acidophilic heterotrophic
      bacteria, Acidiphilium acidophilum and Acidiphilium SJH, to reduce ferric iron to
      ferrous when grown under different culture conditions. METHODS AND RESULTS:
      Bacteria were grown in batch culture, under different aeration status, and in the
      presence of either ferrous or ferric iron. The specific rates of ferric iron
      reduction by fermenter-grown Acidiphilium SJH were unaffected by dissolved oxygen
      (DO) concentrations, while iron reduction by A. acidophilum was highly dependent
      on DO concentrations in the growth media. The ionic form of iron present (ferrous
      or ferric) had a minimal effect on the abilities of harvested cells to reduce
      ferric iron. Whole cell protein profiles of Acidiphilium SJH were very similar,
      regardless of the DO status of the growth medium, while additional proteins were
      present in A. acidophilum grown microaerobically compared with aerobically-grown
      cells. CONCLUSIONS: The dissimilatory reduction of ferric iron is constitutive in
      Acidiphilium SJH while it is inducible in A. acidophilum. SIGNIFICANCE AND IMPACT
      OF THE STUDY: Ferric iron reduction by Acidiphilium spp. may occur in oxygen
      containing as well as anoxic acidic environments. This will detract from the
      effectiveness of bioremediation systems where removal of iron from polluted
      waters is mediated via oxidation and precipitation of the metal.

PMID- 11849361
TI  - Isolation and preliminary characterization of bacteriocins produced by Vibrio
      vulnificus.
AB  - AIMS: The aim of this work was to isolate bacteriocins from the environment that
      would be effective in neutralizing Vibrio vulnificus in seafood. METHODS AND
      RESULTS: Water samples from Wilmington (NC, USA) were plated to determine total
      viable counts and to isolate presumptive Vibrio spp. Isolates containing plasmids
      were checked for antimicrobial activity which was not due to lytic bacteriophage
      or small, non-specific molecules. Three bacteriocin producers were detected and
      their inhibitory spectra determined: IW1 inhibited few strains of V. vulnificus;
      BC1 inhibited several strains of V. vulnificus, V. cholerae and V.
      parahaemolyticus and BC2 inhibited all tested Vibrio spp., Plesiomonas
      shigelloides and Escherichia coli. Loss of inhibitory activity coincided with
      loss of the bacteriocinogenic plasmid. The bacteriocins were found to be between
      1.3 and 9.0 kDa. IW1 was heat labile, while BC1 was moderately stable except at
      extreme temperatures. BC2 was very stable and maintained its activity when
      frozen, autoclaved or exposed to extreme pH values. CONCLUSIONS: Bacteriocins
      have been isolated from environmental isolates of V. vulnificus and V. cholerae.
      BC2, with its broad spectrum and stability, may be useful in neutralizing V.
      vulnificus. SIGNIFICANCE AND IMPACT OF THE STUDY: The results have significance
      in relation to reducing the occurrence of food poisoning caused by V. vulnificus.

PMID- 11849362
TI  - Effects of temperature, pH, water activity and CO2 concentration on growth of
      Rhizopus oligosporus NRRL 2710.
AB  - AIMS: To investigate the effects of temperature, pH, water activity (aw) and CO2
      concentration on the growth of Rhizopus oligosporus NRRL 2710. METHODS AND
      RESULTS: Hyphal extension rates from mycelial and spore inocula were measured on
      media with different aw (approximately 1.0, 0.98 and 0.96) and pH (3.5, 5.5 and
      7.5) incubated at 30, 37 or 42 degrees C in atmospheres containing 0.03, 12.5 or
      25% (v/v) CO2. The effects of environmental conditions on hyphal extension rate
      were modelled using surface response methodology. The rate of hyphal extension
      was very sensitive to pH, exhibiting a pronounced optimum at pH 5.5-5.8. The
      hyphal extension rate was less sensitive to temperature, aw or CO2, exhibiting
      maximum rates at 42 degrees C, a(w) approximately 1.0 and 0.03% (v/v) CO2.
      CONCLUSIONS: The fastest hyphal extension rate (1.7 mm h(-1)) was predicted to
      occur at 42 degrees C, pH 5.85, a(w) approximately 1.0 and 0.03% CO2.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The present work is the first to model the
      simultaneous effects of temperature, pH, aw and CO2 concentration on mould
      growth. The information relates to tempe fermentation and to possible control of
      the microflora in Tanzanian cassava heap fermentations.

PMID- 11849363
TI  - Removal and inactivation of indicator bacteriophages in fresh waters.
AB  - AIMS: The removal and inactivation of faecal coliform (FC) bacteria, enterococci
      (ENT), sulphite-reducing clostridia (SRC), somatic coliphages, F-specific RNA
      bacteriophages and bacteriophages infecting Bacteroides fragilis in fresh waters.
      METHODS AND RESULTS: Removal was studied in two areas of a river. The results
      showed different removal of each group of microbes. Faecal coliform bacteria were
      removed faster than any other, whereas SRC and bacteriophages infecting Bact.
      fragilis were the most persistent. Inactivation was measured by 'in situ'
      experiments, which showed significant differences in survival of the different
      groups of bacterial and bacteriophage indicators. The SRC and bacteriophages were
      more resistant than faecal coliforms and enterococci, with the exception of F
      specific RNA bacteriophages in the summer. Inactivation experiments with pure
      cultures of bacteriophages confirmed that phage B40-8 of Bact. fragilis was the
      most resistant. CONCLUSIONS: Bacteria and bacteriophages show different
      resistance to natural inactivation. The use of phages allows information to be
      obtained in addition to that provided by bacterial indicators. Somatic coliphages
      and phages infecting Bact. fragilis might supply that indicator function.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Confirmation was obtained that
      bacteriophages provided additional information to that provided by bacterial
      indicators to monitor the natural inactivation of viruses and/or pathogens.

PMID- 11849364
TI  - Composition of enterococcal and streptococcal flora from pigeon intestines.
AB  - AIMS: To identify the streptococcal and enterococcal components of the microflora
      from pigeon intestines to species level by tDNA-intergenic polymerase chain
      reaction. METHODS AND RESULTS: Gram-positive coccal strains were isolated from
      the intestines or faeces of 50 different pigeons, all from different lofts, on
      Columbia CNA blood agar. Sodium azide-sensitive enterococci were found to
      constitute the major coccal members of the intestinal flora of pigeons. Forty-two
      of 69 isolates were identified as Enterococcus columbae (84% of animals tested
      positive), while E. cecorum was encountered in 28% of all animals (14 isolates).
      Minor species (less than 10% of pigeons positive) were E. faecalis, E. faecium,
      E. gallinarum, E. casseliflavus, Streptococcus alactolyticus and Strep.
      gallolyticus. Contrary to the species description of E. columbae and E. cecorum,
      some of the strains were found to be motile. Certain other minor differences with
      the species description of E. columbae are also indicated. CONCLUSIONS:
      Enterococcus columbae is the major Gram-positive facultatively anaerobic
      component of the pigeon intestinal flora. Certain phenotypic characteristics
      differ from the original species description. The potentially pathogenic Strep.
      gallolyticus is a minor component of the microflora. Enterococcus faecium and E.
      faecalis are rare in pigeons. SIGNIFICANCE AND IMPACT OF THE STUDY: The
      enterococcal and streptococcal flora of pigeons is composed of mainly host
      specific bacteria. These are not likely to act as zoonotic pathogens nor as
      carriers of antibiotic resistance determinants possibly spreading to humans.

PMID- 11849365
TI  - Differential efficacy of a chlorine dioxide-containing sanitizer against single
      species and binary biofilms of a dairy-associated Bacillus cereus and a
      Pseudomonas fluorescens isolate.
AB  - AIMS: Daily exposure to 100 p.p.m. chlorine dioxide of single species and binary
      biofilms of dairy-associated Bacillus cereus DL5 and Pseudomonas fluorescens M2,
      attached to stainless steel surfaces in a laboratory flow system, was studied.
      METHODS AND RESULTS: Surfaces were sampled daily before and after sanitizer
      treatment and cells and spores dislodged and enumerated by standard methods.
      Duplicate surfaces were prepared for confocal scanning laser microscopy (CSLM)
      and scanning electron microscopy. Higher counts of Ps. fluorescens M2 were
      obtained in single species biofilms, microcolonies stained green (viable) in CSLM
      images and were closely packed on attachment surfaces. By contrast, higher counts
      of B. cereus DL5 were obtained in binary biofilms, microcolonies stained green in
      CSLM images, but were more spread out. Lower spore counts were obtained for B.
      cereus DL5 in binary biofilms. The survival of Ps. fluorescens M2 cells after
      exposure to chlorine dioxide was apparently enhanced by the presence of B. cereus
      DL5 in binary biofilms. By contrast, B. cereus DL5 showed increased
      susceptibility to sanitizer treatment in the presence of Ps. fluorescens M2.
      CONCLUSIONS: Co-cultured bacteria in biofilms influence each other with respect
      to attachment capabilities and sanitizer resistance/susceptibility. SIGNIFICANCE
      AND IMPACT OF THE STUDY: Binary biofilms endemic in food-processing industries
      can survive sanitation regimes and may represent reservoirs of product
      contamination leading to subsequent spoilage and/or food safety risks.

PMID- 11849366
TI  - Mechanisms of killing spores of Bacillus subtilis by acid, alkali and ethanol.
AB  - AIMS: To determine the mechanisms of killing of Bacillus subtilis spores by
      ethanol or strong acid or alkali. METHODS AND RESULTS: Killing of B. subtilis
      spores by ethanol or strong acid or alkali was not through DNA damage and the
      spore coats did not protect spores against these agents. Spores treated with
      ethanol or acid released their dipicolinic acid (DPA) in parallel with spore
      killing and the core wet density of ethanol- or acid-killed spores fell to a
      value close to that for untreated spores lacking DPA. The core regions of spores
      killed by these two agents were stained by nucleic acid stains that do not
      penetrate into the core of untreated spores and acid-killed spores appeared to
      have ruptured. Spores killed by these two agents also did not germinate in
      nutrient and non-nutrient germinants and were not recovered by lysozyme
      treatment. Spores killed by alkali did not lose their DPA, did not exhibit a
      decrease in their core wet density and their cores were not stained by nucleic
      acid stains. Alkali-killed spores released their DPA upon initiation of spore
      germination, but did not initiate metabolism and degraded their cortex very
      poorly. However, spores apparently killed by alkali were recovered by lysozyme
      treatment. CONCLUSIONS: The data suggest that spore killing by ethanol and strong
      acid involves the disruption of a spore permeability barrier, while spore killing
      by strong alkali is due to the inactivation of spore cortex lytic enzymes.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The results provide further information on
      the mechanisms of spore killing by various chemicals.

PMID- 11849367
TI  - Oestrogen receptors, receptor variants and oestrogen actions in the hypothalamic
      pituitary axis.
AB  - Information on oestrogen action has grown exponentially in the past decade, and
      recent studies have begun to define the mechanism of ligand-dependent activation
      and cell-specific effects. Oestrogen-mediated gene transcription in a specific
      tissue depends on several factors, the most important of which is the presence of
      at least one of the two nuclear oestrogen receptor (ER) isoforms, ER(alpha) and
      ERbeta. The presence and levels of specific ER isoform variants, along with
      receptor coactivator, corepressor and integrator proteins, directly modulate
      overall nuclear ER activity. The structure of the ligand, including both
      physiological oestrogens and synthetic oestrogen receptor modulators, influences
      ER interactions with these other proteins and thus determines the biological
      response. Furthermore, peptide and neurotransmitter-stimulated intracellular
      signalling pathways activate specific enzyme cascades and may modify the
      receptors and their interacting proteins, resulting in either independent or
      ligand-enhanced ER-mediated responses. Finally, several rapid effects of
      oestrogen probably occur at the membrane through nongenomic pathways that may or
      may not require the same ER proteins that are found in the nucleus. This review
      concentrates on the pituitary-hypothalamic axis and the genomic effects of
      oestrogen, and discusses the current knowledge of each of these factors in
      determining oestrogen actions in the neuroendocrine system.

PMID- 11849368
TI  - Evidence in favour of a direct input from the ventromedial nucleus to
      gonadotropin-releasing hormone neurones in the ewe: an anterograde tracing study.
AB  - The mechanism by which oestrogen activates the gonadotropin releasing hormone
      (GnRH) neurones to induce the preovulatory luteinizing hormone (LH) surge is not
      understood. Previous work in the ewe has suggested that the primary site of
      action for oestradiol in stimulating the GnRH neurones was in the region of the
      ventromedial nucleus (VMN) within the mediobasal hypothalamus (MBH). In the
      present study, we used anterograde tracing techniques in the ewe to investigate
      whether direct neuronal projections may exist from neurones located in the region
      of the VMN to the GnRH neurones. Following the injection of biotinylated dextran
      amine into the VMN of four ewes, anterogradely labelled fibres were found located
      principally within the ipsilateral diagonal band of Broca (DBB), septum, preoptic
      and anterior hypothalamic areas, and periventricular, paraventricular,
      dorsomedial and arcuate nuclei of the MBH. Dual-labelling for GnRH revealed that
      fibres containing anterograde tracer were adjacent to the soma and/or dendrites
      of approximately 50% of all ipsilateral GnRH neurones located throughout the DBB
      and hypothalamus. Few anterogradely labelled fibres were detected within the
      median eminence. Although such studies cannot define the presence of direct
      synaptic connections between VMN neurones and the GnRH cells, these observations
      support further the hypothesis that oestrogen-sensitive VMN neurones represent a
      direct transsynaptic input to the GnRH cell bodies which are involved in the
      generation of the LH surge in the ewe.

PMID- 11849369
TI  - cDNA array analysis of pineal gene expression reveals circadian rhythmicity of
      the dominant negative helix-loop-helix protein-encoding gene, Id-1.
AB  - The pineal gland is a major output of the endogenous vertebrate circadian clock,
      with melatonin serving as the output signal. In many species, elevated nocturnal
      melatonin production is associated with changes in pineal gene expression. In the
      current study, cDNA array analysis was used in an attempt to identify additional
      genes that exhibit day/night differential expression in the rat pineal gland.
      This revealed 38 candidate genes, including Id-1 (inhibitor of DNA binding and
      differentiation). Id-1 encodes a helix-loop-helix (HLH) protein that lacks a
      basic DNA binding domain and could affect pineal physiology via a dominant
      negative trans-acting regulatory activity. For this reason Id-1 was selected for
      further analysis. Id-1 was expressed in a major population of pineal cells and
      the Id-1 protein was associated with a nuclear complex. The levels of Id-1 mRNA
      and protein exhibit approximately six-fold day/night rhythms. In contrast, the
      related genes Id-2 and Id-3 do not exhibit marked day/night differences in pineal
      expression. Rhythmic Id-1 expression is primarily limited to a C-terminally
      extended splice variant of Id-1, which would restrict the functional output of
      the rhythm to protein binding partners of this isoform of Id-1. Our findings add
      to the body of evidence indicating that transcriptional regulators play a role in
      neuroendocrine rhythms, and extend this by introducing the concept of a dominant
      negative HLH involvement. The rhythm in Id-1 in the pineal gland provides an
      experimental opportunity to identify Id-1-binding partners which may also be
      involved in Id-1 activity in other functional contexts.

PMID- 11849370
TI  - A progestin antagonist blocks vaginocervical stimulation-induced fos expression
      in neurones containing progestin receptors in the rostral medial preoptic area.
AB  - Vaginocervical stimulation (VCS) has a variety of effects on the brain,
      physiology and behaviour. Previous work demonstrated that a progestin antagonist
      blocked neuronal response to VCS (i.e. Fos expression) in the absence of
      progesterone in some neurones, and suggested that some of the effects of VCS on
      the brain are mediated by ligand-independent activation of progestin receptors
      (PRs). Although it had been reported previously that some of the cells in which
      VCS induces Fos expression also contain PRs, it had not been determined if a
      progestin antagonist blocked Fos expression in these particular neurones. The
      purpose of this experiment was to determine if a progestin antagonist decreases
      Fos expression specifically in cells that also express PRs in the preoptic area
      and ventromedial hypothalamus. As has been shown previously, VCS increased Fos
      immunoreactive (ir) expression in the particular areas studied. In the rostral
      medial preoptic area, VCS increased Fos expression in cells that coexpressed PRs,
      as well as in cells that do not. However, in the caudal medial preoptic area, VCS
      only increased Fos expression in cells that did not coexpress PRs. Injection of
      the progestin antagonist, RU 486, decreased Fos expression in the rostral, but
      not caudal medial preoptic area, and it decreased Fos expression only in cells
      that coexpressed PR-ir. In contrast to a previous report, in the present study,
      the progestin antagonist did not inhibit VCS-induced Fos expression in the
      ventromedial hypothalamic area. The results of this experiment suggest that the
      progestin antagonist inhibits VCS-induced Fos expression in some neurones by
      blocking PRs, and they provide further support for the idea that VCS influences
      neuronal response in some cells by ligand-independent activation of PRs in those
      cells.

PMID- 11849371
TI  - Sexually dimorphic activation of galanin neurones in the ferret's dorsomedial
      preoptic area/anterior hypothalamus after mating.
AB  - Male ferrets in breeding condition possess three times as many galanin
      immunoreactive (IR) neurones as oestrous females in the sexually dimorphic
      dorsomedial preoptic area/anterior hypothalamus (dmPOA/AH). Using Fos-IR as a
      marker of activation, we investigated whether mating with intromission
      differentially activates this sexually dimorphic group of galanin-IR neurones in
      male and female ferrets. Male ferrets that intromitted had a significantly
      greater percentage of galanin-IR neurones in the dmPOA/AH that were colabelled
      with nuclear Fos-IR than oestrous females that received an intromission.
      Intromissive stimulation augmented Fos-IR in an equal percentage of galanin-IR
      neurones in both sexes in the medial amygdala (MA) and bed nucleus of the stria
      terminalis (BNST). Peripheral anosmia induced by bilateral occlusion of males'
      nares did not reduce the mating-induced activation of galanin-IR neurones in the
      dmPOA/AH, and there was a significant correlation among individual males between
      intromission duration and the percentage of dmPOA/AH galanin-IR neurones
      colabelled with Fos-IR. Exposure of castrated, testosterone propionate-treated
      male ferrets to either soiled bedding or to volatile odours from oestrous females
      failed to induce nuclear Fos-IR in galanin-IR neurones located in the dmPOA/AH,
      BNST or MA, suggesting that the mating-induced activation of galanin-IR forebrain
      neurones in male ferrets depends more on genital-somatosensory than on olfactory
      inputs. The observed sex dimorphism in the mating-induced activation of galanin
      IR neurones in the dmPOA/AH raises the possibility that these neurones perform a
      mating-dependent function that occurs only in males.

PMID- 11849372
TI  - Decreased corticotropin-releasing factor receptor expression and
      adrenocorticotropic hormone responsiveness in anterior pituitary cells of Wistar
      Kyoto rats.
AB  - The Wistar-Kyoto (WKY) rat shows signs of persistent activation of the
      hypothalamic-pituitary-adrenal axis, but the cause and site of this activation is
      not yet known. Chronically activated corticotrophs generally show blunted
      adrenocorticotropic hormone (ACTH) response to corticotropin releasing factor
      (CRF); therefore, the anterior pituitary responsiveness to ACTH secretagogues,
      CRF and vasopressin, was compared in male WKY and Wistar rats. Anterior pituitary
      CRF binding and CRF receptor mRNA expression was significantly decreased in WKY
      rats. ACTH response to CRF or vasopressin was markedly impaired, and vasopressin
      failed to potentiate the CRF-stimulated ACTH release in cultured WKY anterior
      pituitary cells. In contrast, CRF and vasopressin alone and in combination
      stimulated large, concentration-dependent increases in ACTH release in Wistar
      anterior pituitary cells. By contrast to the decreased ACTH secretory responses,
      steady-state anterior pituitary pro-opiomelanocortin mRNA levels were
      approximately 12-fold greater in WKY rats compared to Wistar rats, and they
      further increased in response to CRF stimulation. These findings suggest that,
      although the WKY rat corticotroph is under a chronic state of activation or
      disinhibition, the in vitro secretory responses to classic ACTH secretagogues are
      impaired.

PMID- 11849374
TI  - Agonist-specific and sexual stage-dependent inhibition of gonadotropin-releasing
      hormone-stimulated gonadotropin and growth hormone release by ryanodine:
      relationship to sexual stage-dependent caffeine-sensitive hormone release.
AB  - Differential utilization of intracellular Ca2+ stores with specific functional
      characteristics could be a potential mechanism for coupling various stimuli to
      specific cellular responses. In the goldfish pituitary, both gonadotropes and
      somatotropes possess multiple intracellular Ca2+ stores that are differentially
      coupled to agonist-evoked exocytosis. We investigated the role of ryanodine
      receptor/Ca2+-release channels (RyR) in basal and gonadotropin-releasing hormone
      (GnRH)-evoked hormone secretion from cultured gonadotropes and somatotropes using
      radioimmunoassay for gonadotropin (GTH-II) and growth hormone (GH). As is the
      case in vivo, the basal and evoked secretion of both hormones varied with
      seasonal reproductive status. GnRH-stimulated hormone release was three-fold
      higher in cells from sexually mature animals compared to those in a sexually
      regressed state. Nanomolar doses of ryanodine evoked significant GTH-II and GH
      secretion, suggesting that ryanodine-sensitive Ca2+ stores can couple to
      exocytosis in both cell types. In gonadotropes, 10 microM ryanodine abolished
      cGnRH-II-evoked GTH-II release in both sexually mature and sexually regressed
      fish, while sGnRH signalling was mediated by ryanodine-sensitive Ca2+ stores in
      cells from sexually regressed fish only. Ryanodine-sensitive Ca2+ stores in
      somatotropes were only involved in cGnRH-II-stimulated GH release during gonadal
      regression. In contrast, sGnRH-stimulated, but not cGnRH-II-stimulated, GH
      release was significantly reduced by 1 microM xestospongin C. Although hormone
      release stimulated by mobilizing caffeine-sensitive Ca2+ pools was also markedly
      seasonal, it was largely independent of ryanodine-sensitive Ca2+ stores.
      Ryanodine-sensitive Ca2+ stores in both cell types are not active downstream of
      ionomycin, BayK 8644, protein kinase C or cyclic adenosine monophosphate
      signalling pathways, suggesting difference from a classical Ca2+-induced Ca2+
      release system. Ours study is the first to suggest that RyR2 may be involved in
      the seasonal plasticity of pituitary function, which may be related to cyclic
      changes observed in reproduction and growth.

PMID- 11849373
TI  - Perinatal malnutrition programs sympathoadrenal and hypothalamic-pituitary
      adrenal axis responsiveness to restraint stress in adult male rats.
AB  - In humans, an altered control of cortisol secretion was reported in adult men
      born with a low birth weight making the hypothalamic-pituitary-adrenal (HPA) axis
      a possible primary target of early life programming. In rats, we have recently
      shown that maternal food restriction during late pregnancy induces both an
      intrauterine growth retardation and an overexposure of fetuses to maternal
      corticosterone, which disturb the development of the HPA axis in offspring. The
      first aim of this work was to investigate, in adult male rats, whether perinatal
      malnutrition has long-lasting effects on the HPA axis activity during both basal
      and stressful conditions. Moreover, as the HPA axis and sympathetic nervous
      system are both activated by stress, the second aim of this work was to
      investigate, in these rats, the adrenomedullary catecholaminergic system under
      basal and stressful conditions. This study was conducted on 4-month-old male rats
      malnourished during their perinatal life and on age-matched control animals.
      Under basal conditions, perinatal malnutrition reduced body weight and plasma
      corticosteroid-binding globulin (CBG) level but increased mineralocorticoid
      receptor (MR) gene expression in CA1 hippocampal area. After 30 min of restraint,
      perinatally malnourished (PM) rats showed increased plasma noradrenaline,
      adrenocorticotropin hormone (ACTH) and corticosterone concentrations similarly as
      controls, but calculated plasma-free corticosterone concentration was
      significantly higher and adrenaline level lower than controls. During the phase
      of recovery, PM rats showed a rapid return of plasma ACTH and corticosterone
      concentrations to baseline levels in comparison with controls. These data suggest
      that in PM rats, an elevation of basal concentrations of corticosterone, in face
      of reduced CBG and probably increased hippocampal MR lead to a much larger impact
      of corticosterone on target cells that mediate the negative-feedback mechanism on
      the activities of both the HPA axis and sympathoadrenal one.

PMID- 11849375
TI  - Regulational effect of ghrelin on growth hormone secretion from perifused rat
      anterior pituitary cells.
AB  - Ghrelin, a novel growth hormone (GH)-releasing peptide, was recently isolated
      from the rat stomach as an endogenous ligand to growth hormone secretagogue
      receptor (GHS-R). Ghrelin specifically stimulates the release of GH from the rat
      anterior pituitary gland, but the regulational effect of ghrelin on GH secretion
      has not yet been clarified. We used a perifusion system to examine the single
      effect and combined effects of ghrelin with growth hormone-releasing hormone
      (GHRH) and somatostatin on GH secretion from rat anterior pituitary cells. The
      increase in GH concentration due to ghrelin stimulation showed a transitory peak
      that was almost the same as that previously reported for GHS, but apparently
      distinct from that of GHRH. Ghrelin (10(-10) M to 10(-8) M) stimulated GH
      secretion from the rat anterior pituitary cells in a dose-dependent manner.
      Serial ghrelin stimulation of the dispersed cells at 1-h intervals decreased the
      GH response, but the response recovered with stimulation at 3-h intervals,
      indicating that ghrelin strongly desensitized cells. Costimulation with ghrelin
      and GHRH elicited neither a synergistic nor an additive GH response from the rat
      pituitary cells. Furthermore, pretreatment to anterior pituitary cells with
      somatostatin strongly abolished ghrelin- and/or GHRH-stimulated GH secretion. In
      this study, we demonstrated that ghrelin caused weaker GH secretion than that
      caused by GHRH, and we also showed that costimulation with GHRH had no additive
      or synergistic effect on GH secretion, suggesting that ghrelin indirectly affects
      coordinated GH release from pituitary gland, as found in vivo.

PMID- 11849376
TI  - Effects of early undernutrition on the brain insulin-like growth factor-I system.
AB  - Undernutrition reduces circulating concentrations of insulin-like growth factor
      (IGF)-I, but how it affects the brain IGF system, especially during development,
      is largely unknown. We have studied IGF-I, IGF-II, IGF receptor and IGF binding
      protein (BP)-2 mRNA expression in the hypothalamus, cerebellum and cerebral
      cortex of neonatal rats that were food restricted beginning on gestational day
      16. One group was refed starting on postnatal day 14. Rats were killed on
      postnatal day 8 or 22. Undernutrition did not produce an overall reduction in
      brain weight at either age but, at 22 days, both the cerebellum and hypothalamus
      weighed significantly less. At 8 days, no change was detected in the central IGF
      axis in response to undernutrition. However, in 22-day-old undernourished rats,
      IGF-I and IGF receptor mRNA expression were increased in both the hypothalamus
      and cerebellum, while IGFBP-2 was decreased, but only in the hypothalamus.
      Refeeding had no effect on any of these parameters. These results suggest that
      the hypothalamus and cerebellum respond to malnutrition and the decrease in
      circulating IGF-I, a peptide fundamental for growth and development, by
      increasing the local production of both the growth factor and its receptor in
      attempt to maintain normal development.

PMID- 11849377
TI  - Toward better dialysis compatibility: advances in the biochemistry and
      pathophysiology of the peritoneal membranes.
AB  - Peritoneal dialysis (PD) has modified our concept of the peritoneal membrane,
      which is now a topic of active research. Peritoneal solute transport
      progressively increases with time on PD, enhances the dissipation of the osmotic
      gradient and, eventually, reduces ultrafiltration capacity. The causes of
      peritoneal membrane failure remain elusive. Recurrent episodes of peritonitis are
      not a prerequisite for the development of ultrafiltration failure. Functionally,
      the changes of the failing peritoneal membrane are best described as an increased
      functional area of exchange for small solutes between blood and dialysate.
      Histologically, these events are associated with vascular proliferation and
      structural changes of pre-existing vessels. Gathered evidence, including
      information on the composition of peritoneal cavity fluids and its dependence on
      the uremic environment, have cast a new light on the molecular mechanisms of
      decline in peritoneal membrane function. Chronic uremia per se modifies the
      peritoneal membrane and increases the functional area of exchange for small
      solutes. Biochemical alterations in the peritoneum inherent to uremia might be,
      at least in part, accounted for by severe reactive carbonyl compounds overload
      originating both from uremic circulation and PD fluid ("peritoneal carbonyl
      stress"). The molecular events associated with long-term PD are similar but more
      severe than those present in chronic uremia without PD, including modifications
      of nitric oxide synthase (NOS) and angiogenic growth factors expression, and
      advanced glycation and lipoxidation of the peritoneal proteins. This review
      focuses on reactive carbonyls and their association with a number of molecular
      changes observed in peritoneal tissues. This hypothetical approach will require
      further testing. Nevertheless, the insights gained on the peritoneal membrane
      offer a new paradigm to assess the effect of uremic toxins on serosal membranes.
      Furthermore, the progresses made in the dissection of the molecular events
      leading to peritoneal membrane failure open new avenues to develop safe, more
      biocompatible peritoneal dialysis technologies.

PMID- 11849378
TI  - Stem cells in the kidney.
AB  - The kidney is derived from the ureteric bud and the metanephrogenic mesenchyme,
      and these two progenitor cells differentiate into more than 26 different cell
      types in the adult kidney. The ureteric bud contains the precursor of the
      epithelial cells of the collecting duct and the renal mesenchyme contains
      precursors of all the epithelia of the rest of the nephron, endothelial cell
      precursors and stroma cells, but the relatedness among these cells is unclear. A
      single metanephric mesenchymal cell can generate all the epithelial cells of the
      nephron (except the collecting duct), indicating that the kidney contains
      epithelial stem cells. It is currently unknown whether these stem cells also are
      present in the adult kidney but experience in other organs makes this likely. It
      also is unclear whether embryonic renal epithelial stem cells can generate other
      cell types, but preliminary studies in our laboratory suggest that they can
      differentiate into myofibroblasts, smooth muscle, and perhaps endothelial cells,
      indicating that they are pluripotent renal stem cells. The important problem to
      be solved now is the identification and location of adult renal stem cells. This
      article discusses work done in other organs and in renal development that we
      believe may be useful for the resolution of this problem.

PMID- 11849379
TI  - L-arginine rescues decreased erythropoietin gene expression by stimulating GATA-2
      with L-NMMA.
AB  - BACKGROUND: NG-monomethyl-L-arginine (L-NMMA) decreases the expression of nitric
      oxide (NO) and cyclic guanosine monophosphate (cGMP) and increases the expression
      of GATA-2 mRNA and levels of GATA-2 binding activity, thereby inhibiting
      erythropoietin (Epo) promoter activity and causing a decrease in the expression
      of Epo protein. In the present study, we examined the effect of L-arginine on Epo
      gene expression in Hep3B cells and BDF1 mice. METHODS: Hep3B cells were incubated
      with and without different concentrations of L-NMMA and/or l-arginine. Anemic
      mice were injected with phosphate-buffered saline (PBS) or L-NAME and L-arginine.
      RESULTS: Incubation with L-NMMA under hypoxic conditions inhibited Epo
      expression, but this inhibition was recovered by the addition of L-arginine.
      Hypoxia induced the secretions of NO and cGMP, but the addition of L-NMMA
      inhibited these inductions, though these inhibitions of NO and cGMP by L-NMMA
      were recovered by the addition of L-arginine. Hep3B cells transfected with the
      Epo promoter/enhancer-luciferase gene had Epo promoter activity. This activity
      was inhibited by L-NMMA, but it could be recovered by the addition of L-arginine.
      L-NMMA induced the binding activity of GATA-2 under hypoxic conditions. This
      binding activity was inhibited by the addition of L-arginine. The addition of
      cGMP inhibited L-NMMA-induced GATA-2 binding activity in a dose-dependent manner.
      The results of an in vivo mouse assay revealed that L-NAME inhibited the
      expression of Epo, but this inhibition of Epo expression by L-NAME was rescued by
      pretreatment with L-arginine. CONCLUSION: L-arginine rescues decreased
      erythropoietin gene expression by stimulating GATA-2 with NG-monomethyl-L
      arginine.

PMID- 11849380
TI  - Effect of early glucocorticoid treatment on MR and GR in late gestation ovine
      kidney.
AB  - BACKGROUND: The ontogeny of the renal mineralocorticoid (MR) and glucocorticoid
      (GR) receptors in the ovine fetus, and the effects of early exposure to synthetic
      or natural glucocorticoids on the expression of these genes in late gestation
      were examined. METHODS: A partial cDNA sequence for the ovine MR was cloned and
      used to generate primers and probes to measure MR mRNA expression by real-time
      polymerase chain reaction (PCR). GR mRNA was also measured. Kidneys were
      collected from ovine fetuses at various stages of gestation (days 60 to 140),
      twin ovine fetuses at 130 days, from ewes treated at days 26 to 28 with either
      saline, dexamethasone or cortisol, and adult sheep. Ligand binding was used to
      determine both GR and MR protein levels in all 130-day-old fetuses and adults.
      RESULTS: No significant changes in the expression of either renal MR or GR were
      detected throughout gestation. Cytosolic protein levels were higher in the fetal
      kidneys than in the adult. There was a significant increase in both fetal MR and
      GR mRNA expression, but not protein levels in kidneys from ewes pretreated with
      dexamethasone. CONCLUSIONS: MR and GR mRNA are expressed throughout development
      in ovine fetal kidneys. Dexamethasone treatment resulted in increased expression
      of MR and GR mRNA but not protein levels. The dissociation between fetal mRNA and
      protein levels, relative to adult kidneys, suggests that it may be confounding to
      draw conclusions based on mRNA levels alone.

PMID- 11849381
TI  - Signal transduction of beta2m-induced expression of VCAM-1 and COX-2 in synovial
      fibroblasts.
AB  - BACKGROUND: beta2 microglobulin (beta2m) amyloidosis is a destructive articular
      disease affecting dialysis patients. We have demonstrated that beta2m increases
      the expression of vascular cell adhesion molecule (VCAM-1) and cyclooxygenase-2
      (COX-2) in human osteoarthritic synovial fibroblasts (SFLs). METHODS: To
      determine the cell signaling pathways, SFLs were incubated with beta2m in the
      presence or absence of various inhibitors for 24 hours. Intracellular calcium
      ([Ca2+]i) was measured by fluorometric techniques and vascular cell adhesion
      molecule-1 (VCAM-1) and cyclooxygenase-2 (COX-2) expression was determined by
      immunohistochemistry and Western blotting. RESULTS: beta2m increased [Ca2+]i
      levels in a dose dependent manner (P < 0.05) in SFLs. BAPTA-AM, a [Ca2+]i
      chelator, completely inhibited beta2m-induced expression of VCAM-1 and COX-2.
      U73122 [phospholipase C (PLC) inhibitor] or 2-APB [specific inhibitor of inositol
      1,4,5-trisphosphate (IP3)-induced [Ca2+]i release] completely blocked the beta2m
      induced increase in [Ca2+]i and the up-regulation of VCAM-1 and COX-2. However,
      pretreatment with staurosporin, a protein kinase C inhibitor, had no effect.
      Disruption of the actin cytoskeleton by treatment with cytochalasin D or
      latrunculin A blocked beta2m up-regulation of VCAM-1 and COX-2. Finally, cells
      treated with phosphatidylinositol-3 kinase (PI-3 kinase) inhibitors wortmannin or
      LY294002 also failed to express VCAM-1 and COX-2. CONCLUSIONS: These results
      demonstrate that IP3-mediated [Ca2+]i release, PI-3 kinase, and actin
      cytoskeleton reorganization are involved in beta2m-induced expression of VCAM-1
      and COX-2 in human SFLs. Understanding the potential pathways by which beta2m
      exerts its inflammatory-like effects may lead to the development of future
      therapies.

PMID- 11849382
TI  - Renal segmental tubular response to salt during the normal menstrual cycle.
AB  - BACKGROUND: It has been suggested that women gain weight and develop peripheral
      edema during the luteal phase of the menstrual cycle because they tend to retain
      sodium and water. However, there is actually no clear evidence for physiological,
      cyclic variations in renal sodium handling during the menstrual cycle. We
      prospectively assessed the changes in segmental renal sodium handling occurring
      during the menstrual cycle in response to changes in salt intake. METHODS: Thirty
      five normotensive women were enrolled. Seventeen women were randomized and
      studied in the follicular and 18 in the luteal phases of their menstrual cycle.
      All women were assigned at random to receive a low (40 mmol/day) or a high (250
      mmol/day) sodium diet for seven days on two consecutive menstrual cycles. Renal
      sodium handling and hemodynamics were measured at the end of each diet period.
      RESULTS: The changes in sodium intake induced comparable variations in sodium
      excretion in both phases of the menstrual cycle. In the follicular phase, the
      increase in salt intake was associated with no change in renal hemodynamics, an
      increased fractional excretion of lithium (FELi) and a decreased fractional
      distal reabsorption of sodium (FDRNa), suggesting that sodium reabsorption is
      reduced both in the proximal and the distal tubules. In contrast, in the luteal
      phase, the renal response to salt was characterized by a significant renal
      vasodilation and a marked salt escape from the distal nephron, compared to the
      women investigated in the follicular phase (P < 0.01). Sodium reabsorption by the
      proximal nephron was not reduced as indicated by the unchanged FELi. CONCLUSIONS:
      These results show that the segmental renal handling of sodium differs markedly
      in the two phases of the menstrual cycle. They suggest that the female hormones
      modulate the renal handling of sodium at the proximal and distal segments of the
      nephron in young normotensive women.

PMID- 11849383
TI  - Impairment of vascular regeneration precedes progressive glomerulosclerosis in
      anti-Thy 1 glomerulonephritis.
AB  - BACKGROUND: It has been proposed that glomerular hemodynamic changes or
      glomerular growth response may promote the development of glomerulosclerosis,
      irrespective of its etiology. Further experimental models are needed to clarify
      the cellular and molecular mechanisms that lead to progressive glomerulosclerosis
      with an irreversible course. We designed a model of irreversible
      glomerulosclerosis, using anti-Thy-1.1 injection followed by uninephrectomy, and
      examined the role of glomerular endothelial cell responses in the process of
      progressive sclerotic changes. METHOD: Rats were injected with anti-Thy-1.1
      monoclonal antibody, 1-22-3, and 30 minutes later, unilateral nephrectomy (one
      kidney group) or sham operation (two-kidney group) was performed. Rats were
      sacrificed for histological examination on days 3, 14, 56, and 84 after
      injection. The density of the glomerular capillary tuft was assessed by
      immunofluorescent staining for endothelial specific antigens. The mRNA expression
      of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1
      (VCAM-1), platelet-endothelial cell adhesion molecule-1 (PECAM-1), and vascular
      endothelial growth factor (VEGF) also was followed up by reverse transcription
      polymerase chain reaction (RT-PCR). RESULTS: Semiquantitative analysis revealed
      that the capillary density and mRNA expression of PECAM-1, VCAM-1 and VEGF were
      significantly lower in the one-kidney group compared to the two-kidney group on
      day 14. On day 84, progressive glomerulosclerotic lesions were found, followed by
      a decrease of the capillary density in the one-kidney group, while the glomerular
      architecture recovered to an almost normal state in the two-kidney group.
      CONCLUSIONS: Progressive glomerulosclerosis can be induced in the rat by a one
      shot injection of anti-Thy 1.1 monoclonal antibody followed by unilateral
      nephrectomy. This model shows that there is a positive association between
      impairment of vascular regeneration and the development of glomerulosclerosis.

PMID- 11849384
TI  - Human renal epithelial cells express iNOS in response to cytokines but not
      bacteria.
AB  - BACKGROUND: Epithelial cells form the mucosal barriers that prevent the entry of
      mucosal pathogens, and respond to bacterial infections by producing various host
      defense molecules. In this study, we examined the inducible nitric oxide synthase
      (iNOS) response of primary human renal tubular epithelial cells (HRTEC) following
      infection with uropathogenic Escherichia coli Hu734, or stimulation with
      lipopolysaccharide (LPS) or cytokines. METHODS: Induction of iNOS was examined by
      RT-PCR, Western blot, immunohistochemistry and nitrite measurements. The effects
      of endogenously produced nitric oxide (NO), and exogenously applied DETA/NO, SIN
      1 and H2O2 on cell viability were analyzed using a respiration assay. RESULTS:
      HRTEC did not produce NO following infection with E. coli Hu734, LPS alone, or in
      combination with interferon-gamma (IFN-gamma), even though these agents caused a
      marked increase in iNOS expression by RAW 264.7, a macrophage cell line. In
      contrast, iNOS protein and mRNA expression by HRTEC increased after exposure to a
      cytokine mixture consisting of interleukin (IL)-1beta, tumor necrosis factor
      alpha (TNF-alpha) and IFN-gamma. This was due to the combination of IL-1beta and
      IFN-gamma, but the individual cytokines had no effect. Inducible NOS-expressing
      cell cultures showed reduced viability, and this effect was inhibited with the
      NOS inhibitor L-NMMA in RAW 264.7 cells, but not in HRTEC. HRTEC were more
      sensitive to oxidative stress induced by H2O2 than to nitrogen stress induced by
      DETA/NO. CONCLUSIONS: We conclude that uropathogenic E. coli that attach to HRTEC
      fail to directly activate iNOS expression, and that iNOS expression during
      bacterial infection is more likely to result from stimulation by local cytokines
      such as IL-1beta and IFN-gamma.

PMID- 11849385
TI  - C5a delays apoptosis of human neutrophils by a phosphatidylinositol 3-kinase
      signaling pathway.
AB  - BACKGROUND: Studies have shown that survival factors including cytokines and
      growth factors delay apoptosis of human neutrophils via induction of the
      phosphatidylinositol-3 kinase (PI 3-K)/Akt pathway. In the present study, we
      explored whether complement fragment C5a has a modulatory effect on neutrophil
      apoptosis through this signaling pathway. METHODS: Human neutrophils were
      isolated and treated with C5a for up to 24 hours, with or without wortmannin, a
      PI 3-K inhibitor, and staurosporine, a caspase-9 activator. Apoptosis was
      quantified by flow cytometry, using propidium iodide nuclear staining, and
      confirmed by the detection of DNA fragmentation on gel electrophoresis. PI 3-K
      downstream signaling events were evaluated by measuring the expression of
      cytosolic total and phosphorylated Akt and Bad proteins by Western blot analyses,
      and caspase-9 activity. RESULTS: C5a inhibited neutrophil apoptosis in a dose-
      and time-dependent manner. The anti-apoptotic effects of C5a were markedly
      abrogated in the presence of wortmannin. Brief stimulation of neutrophils with
      C5a induced phosphorylation of Akt and Bad proteins through a PI 3-K-dependent
      pathway. Caspase-9 activity was minimal in C5a-treated cells, but markedly
      increased following PI 3-K inhibition by wortmannin. Finally, C5a reduced caspase
      9 activity in staurosporine-treated cells. CONCLUSIONS: This study demonstrates
      that C5a inhibits neutrophil apoptosis via a PI 3-K signaling pathway. This
      effect may be an important mechanism that improves cell survival and function in
      the inflammatory milieu.

PMID- 11849386
TI  - Metallothionein isoform 3 and proximal tubule vectorial active transport.
AB  - BACKGROUND: Metallothionein isoform 3 (MT-3) is expressed in the proximal tubule
      cells of the human kidney. The goal of the present study was to further
      characterize the basal expression of MT-3 in the proximal tubule and to determine
      if MT-3 participates in the maintenance of proximal tubule cell function.
      METHODS: Expression of MT-3 mRNA was determined in the intact proximal tubule
      using microdissection and reverse transcription-polymerase chain reaction (RT
      PCR). Basal expression of MT-3 mRNA and protein was determined in cultured human
      proximal tubule (HPT) cells and an immortalized proximal tubular cell line, HK-2
      cells, using RT-PCR and immunoblotting. The MT-3 gene was stably transfected into
      the HK-2 cell line using the pcDNA3.1/Hygro (+) vector. RESULTS: MT-3 mRNA was
      detected in the proximal tubule of the in situ kidney with relative expression in
      excess to that of the beta-actin housekeeping gene. The mortal HPT cells were
      shown to express both MT-3 mRNA and protein and to form domes, while immortal HK
      2 cells were shown to have no expression of MT-3 mRNA and protein nor to form
      domes. The stable transfection of MT-3 in HK-2 restored MT-3 expression and dome
      formation to the HK-2 cells. CONCLUSIONS: MT-3 mRNA is present in the human
      proximal tubule, and MT-3 expression is involved in the transport function of a
      human renal cell line that retains properties of the proximal tubule.

PMID- 11849387
TI  - Addition of AT1 blocker fails to overcome resistance to ACE inhibition in
      adriamycin nephrosis.
AB  - BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors provide
      renoprotection, but there is considerable interindividual variability in
      therapeutic efficacy, with residual proteinuria and progressive renal function
      loss in many individuals. This requires additional strategies to optimize therapy
      response, particularly for individuals with a poor response to ACE inhibition. We
      studied whether co-treatment with an angiotensin II subtype 1 (AT1) receptor
      antagonist (AII-A) improves the individual antiproteinuric response of maximal
      ACE inhibition in established adriamycin nephrosis. METHODS: Rats were instituted
      on lisinopril (75 mg/L) six weeks after disease induction. After two weeks rats
      were re-stratified for residual proteinuria to continue this regimen, to a higher
      dose of lisinopril (150 mg/L) or to co-treatment with the AII-A L 158,809 for
      another four weeks. Groups on monotherapy AII-A and vehicle served as controls
      (all groups N=15). RESULTS: Lisinopril lowered proteinuria by 63% from 741 to 246
      g/day (range of percentage change -90 to +2%). Neither increasing the dose of the
      ACE inhibitor nor addition of AII-A to ACE inhibition improved the
      antiproteinuric efficacy on a group or individual level: non-responders remained
      non-responders. All drug categories reduced hard end-points of focal
      glomerulosclerosis to a similar degree. CONCLUSIONS: ACE inhibition has variable
      renal protective efficacy in the adriamycin model. Neither increasing the dose of
      the ACE inhibitor beyond the optimal level nor co-treatment with AII-A overcome
      the individual therapy resistance. Thus, in established adriamycin nephrosis,
      blockade of the renin-angiotensin system at two different levels offers no
      additional benefit over ACE inhibition alone, either on the group or individual
      level.

PMID- 11849388
TI  - Fibronectin accumulation in glomerulosclerotic lesions: self-assembly sites and
      the heparin II binding domain.
AB  - BACKGROUND: Glomerulosclerosis is a severe complication of many immunologically
      mediated kidney diseases, eventually resulting in loss of renal function. In
      chronic graft-versus-host disease (GvHD) in mice, a model for human lupus
      nephritis, the end-stage sclerotic lesions were previously shown to contain large
      amounts of fibronectin (FN). This study investigated a domain-specific
      accumulation process of circulating plasma FN (pFN) in sclerotic lesions.
      METHODS: GvHD mice were injected with FITC-conjugated pFN or pFN-fragments, with
      or without heparin pre-incubation. pFN fragments were generated by digestion of
      pFN by cathepsin D, after which the fragments were separated on a heparin
      affinity column. Thus, two batches of fragments were obtained with either low or
      high affinity for heparin. RESULTS: FN accumulation was accompanied by an up
      regulated expression of integrin alpha5beta1, the FN receptor, in the periphery
      of sclerotic lesions. pFN-FITC injected into GvHD mice was trapped in sclerotic
      glomeruli within 24 hours. Both heparin and non-anti-coagulant heparin blocked
      the accumulation of pFN-FITC, indicating that the protective effect of heparin in
      the trapping of FN is independent of its anticoagulant properties, and probably
      results from preventing direct binding of FN in the sclerotic lesions. To
      investigate whether FN binds in the glomerulus via the heparin-binding regions,
      pFN fragments were generated and injected into GvHD mice. Whereas the fraction
      with high affinity for heparin did not accumulate in the sclerotic glomeruli, the
      fraction with low affinity for heparin did. Partial sequencing of the isolated
      peptides showed that in the glomerulus fibronectin does not bind via the heparin
      II binding region. CONCLUSIONS: We hypothesize that the protective effect of
      heparin treatment may be the result of steric hindrance of the specific binding
      sites, that is, the I1-5 and/or III1 self-assembly sites of FN.

PMID- 11849389
TI  - Effects of human soluble thrombomodulin on experimental glomerulonephritis.
AB  - BACKGROUND: Coagulation and inflammation are both important processes that
      contribute to glomerular injury. The present study was performed to evaluate the
      effects of recombinant human soluble thrombomodulin (RHS-TM) in a lethal model of
      thrombotic glomerulonephritis and to investigate the possible mechanisms.
      METHODS: Thrombotic glomerulonephritis was induced in rats by administration of
      lipopolysaccharide and rabbit anti-rat glomerular basement membrane antibody. One
      hour later, RHS-TM or heparin was administered, and the histological findings,
      renal functions, and coagulation parameters were evaluated. To evaluate the
      contribution of carboxypeptidase R (CPR) to the results obtained in rats treated
      with RHS-TM, plasma CPR levels were measured. Then, carboxypeptidase inhibitor
      (CPI), which prevents the function of CPR, was administered. RESULTS: Massive
      glomerular thrombosis and lung hemorrhage developed within five hours of disease
      induction, and all rats died within 24 hours. RHS-TM (3 mg/kg) prevented the
      progression of the disease and all rats survived. Heparin (250 U/kg/h) showed
      similar anti-thrombotic effect, but induced massive hemorrhage in the lungs or
      stomach. RHS-TM attenuated leukocyte/neutrophil infiltration in the glomerulus
      but heparin did not, suggesting that RHS-TM has anti-inflammatory properties. CPR
      levels in plasma were about threefold higher in rats treated with RHS-TM compared
      to those in rats treated with heparin. Furthermore, the inhibitory effect of RHS
      TM on leukocyte/neutrophil infiltration was significantly diminished by injection
      of CPI. CONCLUSION: RHS-TM effectively attenuates the injuries of thrombotic
      glomerulonephritis in rats. The results indicate that RHS-TM, in addition to its
      anti-thrombotic action, may exert its anti-inflammatory properties by converting
      proCPR to CPR, which then inactivates anaphylatoxins. RHS-TM is a potential novel
      therapeutic tool for thrombotic glomerular injury and related disorders.

PMID- 11849390
TI  - TNF-alpha--accelerated apoptosis abrogates ANCA-mediated neutrophil respiratory
      burst by a caspase-dependent mechanism.
AB  - BACKGROUND: Tumor necrosis factor (TNF)-alpha rapidly primes neutrophils (PMN)
      for an anti-neutrophil cytoplasmic antibody (ANCA)-induced respiratory burst and
      is thus proinflammatory. TNF-alpha also progressively accelerates apoptosis. We
      investigated the effect of TNF-alpha-mediated apoptosis on ANCA antigen
      expression and on ANCA-induced superoxide generation in human PMN. METHODS: PMN
      were brought to apoptosis by 10 ng/mL of TNF-alpha or a combination of TNF-alpha
      and 2.5 microg/mL cycloheximide, a protein synthesis inhibitor, or cycloheximide
      alone for three hours. Apoptosis and ANCA antigen expression were assessed by
      fluorescence-activated cell sorting (FACS) and microscopy. Superoxide was
      determined with the ferricytochrome C assay. RESULTS: TNF-alpha with
      cycloheximide for three hours caused apoptosis in 87% PMN compared to 2% in
      untreated controls (N=18; P < 0.01). Accelerated apoptosis was associated with an
      increase in ANCA-antigen expression for both proteinase 3 and myeloperoxidase (P
      < 0.05). Nevertheless, apoptosis was paralleled by a decreased proteinase 3 and
      myeloperoxidase ANCA-induced respiratory burst (P < 0.05). Furthermore,
      superoxide release in response to immune complexes, phorbol ester (PMA), and
      bacterial peptide (FMLP) was significantly decreased. Blocking caspase-3 activity
      prevented apoptosis in TNF-alpha with cycloheximide-treated cells (83% to 2%) and
      prevented compromised respiratory burst in response to ANCA. Caspase-3 inhibition
      abrogated apoptosis-mediated ANCA antigen up-regulation (PR3 141.6 +/- 34.1 MFI
      to 33.9 +/- 7.8; MPO 48.3 +/- 12.9 MFI to 11.9 +/- 3.2, N=6, P < 0.05).
      CONCLUSIONS: TNF-alpha-accelerated apoptosis was associated with increased ANCA
      antigen expression but with down-regulated respiratory burst activity in response
      to ANCA. Specific inhibition of apoptosis by caspase-3 blockade prevented the
      increase in ANCA-antigen expression and preserved the capability of generating
      superoxide, thereby establishing a causative role for apoptosis. We suggest that
      TNF-alpha exhibits dual actions by both priming and terminating ANCA-mediated
      activation of human PMN.

PMID- 11849391
TI  - Selectins mediate macrophage infiltration in obstructive nephropathy in newborn
      mice.
AB  - BACKGROUND: Urinary tract obstruction during development leads to tubular atrophy
      and causes interstitial fibrosis. Macrophage infiltration into the interstitium
      plays a central role in this process. Selectins, a family of three adhesion
      molecules, are involved in leukocyte recruitment to sites of inflammation and
      immune activity. We investigated the role of selectins in obstructive nephropathy
      in newborn mice. METHODS: Triple selectin-deficient mice (EPL-/-), L-selectin
      deficient mice (L-/-) and wild type mice (WT) were subjected to complete
      unilateral ureteral obstruction (UUO) or sham operation within the first 48 hours
      of life, and were sacrificed 5 and 12 days later. Kidneys were removed, and
      sections were stained for macrophage infiltration (mAb F4/80), apoptosis (TUNEL),
      tubular atrophy (periodic acid-Schiff) and interstitial fibrosis (Masson
      trichrome). RESULTS: Selectin deficient mice showed a marked reduction in
      macrophage infiltration into the obstructed kidney compared to WT at day 5 and
      day 12 after UUO. Tubular apoptosis was strongly reduced in EPL-/- at day 5 after
      UUO, and in EPL-/- and L-/- at day 12 after UUO when compared to WT. The number
      of apoptotic tubular cells was correlated with macrophage infiltration,
      suggesting that macrophages stimulate tubular apoptosis in obstructive
      nephropathy. In addition, tubular atrophy and interstitial fibrosis were
      significantly diminished in EPL-/- and L-/- compared to WT at day 12 after UUO.
      CONCLUSION: Following UUO, selectins mediate macrophage infiltration into the
      obstructed kidney, which in turn may induce tubular apoptosis, tubular atrophy
      and interstitial fibrosis.

PMID- 11849392
TI  - Effects of oxalate on the re-initiation of DNA synthesis in LLC-PK1 cells do not
      involve p42/44 MAP kinase activation.
AB  - BACKGROUND: Oxalate interaction with renal epithelial cells results in a program
      of events that include alterations in gene expression, re-initiation of DNA
      synthesis, cell growth and apoptosis. Our studies focused on understanding the
      mechanisms involved in the oxalate-induced re-initiation of the DNA synthesis.
      The effects of oxalate alone or in combination with epidermal growth factor
      (EGF), platelet-derived growth factor (PDGF) and insulin were investigated to
      determine whether oxalate utilized the p42/44 mitogen activated protein (MAP)
      kinase pathway, which is a common pathway used by a majority of the mitogens.
      METHODS: LLC-PK1 cells (a renal epithelial cell line of porcine origin) were
      exposed to oxalate in the presence or absence of three established growth
      factors, EGF, insulin and PDGF, and of the transcription/translation inhibitors,
      actinomycin-D and cycloheximide. DNA synthesis was assessed by [3H]-thymidine
      incorporation. p42/44 MAP kinase activity was assessed by super-shift analysis as
      well as by immunocomplex kinase assay. RESULTS: Exposure of growth-arrested LLC
      PK1 cells to oxalate resulted in the re-initiation of the DNA synthesis was
      abolished by [corrected] pretreatment with transcription/translation inhibitors.
      Oxalate (1 mmol/L), EGF (50 ng/mL) and insulin (100 ng/mL) stimulated DNA
      synthesis in growth-arrested LLC-PK1 cells, while PDGF (50 ng/mL) had no effect.
      Effects of EGF and oxalate on DNA synthesis were additive. In contrast, oxalate
      and insulin had antagonistic effects on DNA synthesis. Additionally, oxalate did
      not activate the p42/44 MAP kinase pathway while EGF stimulated this pathway.
      CONCLUSIONS: These findings demonstrate that oxalate does not activate the p42/44
      MAP kinase pathway, and the effects of oxalate are mediated by pathways that are
      distinct from those of EGF, PDGF and insulin.

PMID- 11849393
TI  - Indomethacin protects permeability barrier from focal segmental
      glomerulosclerosis serum.
AB  - BACKGROUND: Eicosanoids are believed to play a role in the pathophysiology of
      several models of glomerular disease. The cyclooxygenase inhibitor indomethacin
      reduces proteinuria in patients with focal segmental glomerulosclerosis (FSGS) or
      other glomerular diseases. We have shown that sera of some patients with FSGS
      significantly increase glomerular albumin permeability (Palb) in an in vitro
      assay. METHODS: To determine the role of eicosanoids in the increased Palb caused
      by the FSGS factor, glomeruli were isolated from normal rats, preincubated with
      indomethacin, then incubated with FSGS serum or normal serum and Palb was
      calculated. To study the direct effect of individual eicosanoids on Palb,
      glomeruli were incubated with prostaglandin E2, prostaglandin F2alpha or a
      thromboxane A2 mimetic, and Palb was calculated. In the final set of experiments,
      normal glomeruli were preincubated with the thromboxane synthase inhibitor
      furegrelate, incubated with FSGS serum, and Palb was calculated. RESULTS:
      Preincubation of isolated glomeruli with either the cyclooxygenase inhibitor
      indomethacin or the thromboxane synthase inhibitor furegrelate protected
      glomeruli from the increase in Palb caused by FSGS serum. Each of the three
      principal glomerular eicosanoids significantly increased Palb of isolated
      glomeruli. CONCLUSIONS: These studies implicate a product of the cyclooxygenase
      pathway of arachidonic acid metabolism as mediating the increased Palb caused by
      FSGS serum in our in vitro assay and possibly the proteinuria seen in patients
      with FSGS.

PMID- 11849394
TI  - Effects of reduction of renal mass on renal oxygen tension and erythropoietin
      production in the rat.
AB  - BACKGROUND: It is well known that the anemia of chronic renal failure is
      associated with a blunted erythropoietin response. However, it is not clear why
      this response is blunted. Oxygen tension is an important regulator of
      erythropoietin production and release, but the effect of reduced renal mass on
      renal tissue oxygen tensions is currently unknown. METHODS: A computer-based
      simulation was used to determine how alterations in filtration fraction might
      impact on renal tissue oxygen tensions. In addition, direct measurements of
      oxygen tension with needle electrodes were employed, as well as conventional
      physiological measurements and ELISA measurements of plasma and tissue
      erythropoietin concentrations in rats subjected to 5/6th nephrectomy. RESULTS:
      Remnant kidney rats had 39% and 52% decreases in tissue and plasma erythropoietin
      concentrations, respectively, that correlated with 73% increased oxygen tensions
      in both cortex and outer medulla in the remnant kidney (all P < 0.01).
      Estimations of filtration fraction were decreased by approximately 36% in the
      rats bearing remnant kidneys. CONCLUSIONS: Higher oxygen tensions were observed
      in the remnant kidneys. We suggest that higher oxygen tensions are caused by a
      decrease in filtration fraction, and that these higher tissue oxygen tensions
      result in decreased renal erythropoietin production and anemia.

PMID- 11849395
TI  - Nephron specific regulation of chloride channel CLC-K2 mRNA in the rat.
AB  - BACKGROUND: This study investigated the influence of salt intake on the nephron
      specific gene expression of the kidney chloride channel CLC-K2. To this end, male
      Sprague-Dawley rats were fed a low (0.02% wt/wt), normal (0.6% wt/wt), or high
      salt (8% wt/wt) diet for ten days, or they received the loop diuretic furosemide
      (12 mg/kg/day) for six days. METHODS: Expression and regulation of messenger RNA
      for CLC-K2 was demonstrated by RNase protection assay and in situ hybridization
      in kidney cortex, outer medulla and inner medulla. Tubular localization and
      regulation were determined precisely by reverse transcription-polymerase chain
      reaction (RT-PCR) and real time PCR of microdissected nephron segments. RESULTS:
      In situ hybridization analysis and RNase protection assay of the total kidney
      revealed a down-regulation of CLC-K2 mRNA in the high salt diet rats and an up
      regulation of CLC-K2 mRNA in furosemide treated rats, which were restricted to
      the outer medulla. Microdissection of collagenase treated kidney revealed CLC-K2
      mRNA expression in the outer medullary thick ascending limb (mTAL), cortical
      thick ascending limb (cTAL), distal convoluted tubule (DCT), connecting tubule
      and cortical collecting duct (CNT/CCD), and outer medullary collecting duct
      (OMCD), whereas no signals were detected in proximal convoluted and straight
      tubules (PCT and PST), descending thin limb from the outer medulla (dTL),
      descending and ascending thin limb from the inner medulla (TL), inner medullary
      collecting duct (IMCD) and glomeruli (glom). Using RT-PCR and real time PCR, the
      changing levels of CLC-K2 mRNA after furosemide treatment or high salt diet were
      restricted to the mTAL, whereas CLC-K2 mRNA levels in cTAL and OMCD were not
      changed in furosemide or high salt rats compared to time paired controls.
      CONCLUSIONS: Given that CLC-K2 expressed in the thick ascending limb of Henle's
      loop is responsible for net chloride reabsorption in this part of the nephron,
      our findings suggest that in states of surplus salt and in states of severe salt
      deprivation, selective regulation of CLC-K2 mRNA plays a role in the adaptation
      of the kidney to different salt loads.

PMID- 11849396
TI  - Effects of antihypertensive therapy on intrarenal angiotensin and bradykinin
      levels in experimental renal insufficiency.
AB  - BACKGROUND: Whereas angiotensin converting enzyme inhibitors and angiotensin type
      1 receptor antagonists have beneficial effects in the remnant model of renal
      failure, calcium channel blockers do not consistently improve renal disease in
      this model. This study examined whether these different means of blood pressure
      reduction have different effects on renal levels of angiotensin (Ang) and
      bradykinin peptides. METHODS: Rats subjected to five-sixths nephrectomy were
      divided into groups with similar hypertension and proteinuria at 4 to 5 weeks.
      They then received either no treatment, or enalapril, losartan or nifedipine for
      2 weeks. Following repeat measurements of proteinuria and blood pressure, Ang II
      and bradykinin peptides were measured in the remnant kidney and renin, Ang II,
      and aldosterone were measured in the plasma. RESULTS: All three drugs had
      equivalent blood pressure-lowering effects. Enalapril and losartan reduced
      proteinuria but nifedipine did not. Reduction of proteinuria in rats treated with
      enalapril and losartan was associated with a reduction in Ang II levels in both
      the peri-infarct and intact portions of the remnant kidney. By contrast,
      nifedipine increased Ang II levels in the intact portion of the remnant kidney.
      Losartan reduced bradykinin levels in the peri-infarct portion of the remnant
      kidney while enalapril reduced bradykinin levels in the intact portion of the
      remnant kidney. Nifedipine had no effect on intrarenal bradykinin levels.
      CONCLUSIONS: The differential effects of enalapril, losartan and nifedipine on
      proteinuria and intrarenal Ang II and bradykinin levels suggest that the ability
      of an antihypertensive to decrease proteinuria may depend on its ability to
      decrease kidney Ang II and bradykinin levels.

PMID- 11849397
TI  - Cerebral blood flow and vasodilatory capacity in anemia secondary to chronic
      renal failure.
AB  - BACKGROUND: Our previous study reported that cerebral oxygen extraction fraction
      (OEF) increased in hemodialysis patients with anemia. The increased OEF suggests
      that the cerebral vasodilatory capacity might be impaired in these patients. To
      clarify this issue, we measured the CO2 response in patients with anemia
      secondary to chronic renal failure (CRF) using positron emission tomography
      (PET). METHODS: Ten anemic patients with CRF (6 females and 4 males) and 6 age
      matched normal controls were studied. The underlying diseases of CRF were
      glomerulonephritis in 8 patients, systemic lupus erythematosus (SLE) in one
      patient, and hypertension in one patient; in this cohort, 5 patients were on
      hemodialysis treatment and the remaining 5 patients were in a pre-hemodialysis
      state. The cerebral blood flow (CBF) was measured by the O-15 H2O bolus injection
      method with each patient in a resting state and during 5% CO2 inhalation. The CO2
      response was estimated as the percentage change of CBF per 1 mm Hg change of
      PaCO2. RESULTS: The CO2 response was significantly attenuated in anemic patients
      with CRF in comparison to the normal controls, and it inversely correlated with
      the severity of anemia. There was no significant difference in the CO2 response
      between the hemodialysis and pre-hemodialysis patients. The CO2 response
      significantly correlated with CBF and the cerebral metabolic rate for oxygen
      (CMRO2) at rest, however, it did not correlate with OEF and cerebral blood volume
      (CBV). CONCLUSIONS: The present study revealed the existence of a reduced
      cerebral vasodilatory capacity in anemic patients with CRF, suggesting that
      chronic hypoxic brain damage might play a role in the impaired cerebrovascular
      response to CO2.

PMID- 11849398
TI  - Vascular endothelial growth factor production and regulation in human peritoneal
      mesothelial cells.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF) was recently found in
      peritoneal effluents of peritoneal dialysis (PD) patients. It was suggested that
      human peritoneal mesothelial cells (HMC) contribute to the intraperitoneal
      production of VEGF, which may augment vascular permeability, vasodilation and
      neoangiogenesis in the peritoneal membrane. The present study was designed to
      assess the influence of proinflammatory cytokines, thrombin, d-glucose and
      glycated albumin in the regulation of VEGF synthesis in primary HMC cultures.
      METHODS: VEGF antigen concentrations were measured in the cell supernatant by
      ELISA and VEGF mRNA expression was evaluated by real time RT-PCR. RESULTS:
      Incubation of HMC with interleukin-1alpha (IL-1alpha; 10 to 100 U/mL), tumor
      necrosis factor-alpha (TNF-alpha; 500 to 1000 U/mL) or thrombin (1 to 10 U/mL)
      resulted in a time (24 to 72 hours) and concentration dependent increase in VEGF
      synthesis. In contrast, d-glucose (30 to 90 mmol/L), which is commonly used as an
      osmotic agent in peritoneal dialysis, was not able to up-regulate VEGF
      expression. High glucose levels even decreased VEGF production. However, exposure
      of HMC to Amadori-modified glycated albumin, which is generated in the peritoneal
      cavity in the presence of glucose-based dialysis solutions, resulted in a dose
      and time dependent increase in VEGF mRNA expression and antigen secretion.
      CONCLUSIONS: These results demonstrate, to our knowledge for the first time, that
      glycated serum albumin, not glucose, increases VEGF production in HMC. HMC play
      an important role as a source of intraperitoneal VEGF synthesis, and VEGF
      expression also is up-regulated in the presence of proinflammatory cytokines and
      thrombin. Additionally, these results confirm clinical data that the continuous
      exposure of the peritoneal membrane to glucose-based dialysis solutions is an
      important stimulus for VEGF expression. However, it is not glucose per se, but
      nonenzymatic glycation products like glycated albumin that up-regulate VEGF
      expression.

PMID- 11849399
TI  - Urinary excretion of angiotensinogen reflects intrarenal angiotensinogen
      production.
AB  - BACKGROUND: In rats maintained on a high salt diet (H/S) to suppress basal renal
      angiotensinogen levels, angiotensin II (Ang II) infusion for 13 days increased
      renal angiotensinogen mRNA and protein, thus providing a mechanism for further
      augmentation of intrarenal Ang II levels. The present study tested the hypothesis
      that enhanced intrarenal angiotensinogen formation during Ang II infusion is
      reflected by secretion into the tubular fluid leading to increased urinary
      excretion of angiotensinogen (UAGT). METHODS: The effects of chronic Ang II
      infusion were examined on kidney and plasma Ang II levels and UAGT in male
      Sprague-Dawley rats maintained on an 8% salt diet for three weeks (N=10).
      Following one week on the H/S diet, Ang II (40 ng/min) was administered for two
      weeks via an osmotic minipump to one group (H/S + Ang II, N=5), while the
      remaining rats were sham-operated (H/S + Sham, N=5). Additionally, a control
      group was prepared with normal salt diet and sham-operation (N/S + Sham, N=5).
      RESULTS: H/S alone did not alter systolic blood pressure (BP) (103 +/- 2 vs. 104
      +/- 2 mm Hg), while Ang II infusion to H/S rats significantly increased systolic
      BP from 103 +/- 2 to 154 +/- 2 after two weeks. Intrarenal Ang II content in H/S
      + Ang II was significantly greater than H/S + Sham (435 +/- 153 vs. 65 +/- 14
      fmol/g). Ang II infusion significantly increased UAGT (4.0 +/- 0.5 vs. 1.0 +/-
      0.2 nmol Ang I/day by radioimmunoassay of generated Ang I; 57 +/- 15 vs. 14 +/- 2
      densitometric units by Western blotting analysis) compared to Sham. UAGT by
      radioimmunoassay was highly correlated with kidney Ang II content (r=0.79); but
      not with plasma Ang II concentration (r=0.20). CONCLUSIONS: These data
      demonstrate that chronic Ang II infusion increases urinary excretion rate of
      angiotensinogen, and suggest that UAGT provides a specific index of intrarenal
      angiotensinogen production in Ang II-dependent hypertension.

PMID- 11849400
TI  - Endothelial dysfunction and hypertension in 5/6 nephrectomized rats are mediated
      by vascular superoxide.
AB  - BACKGROUND: Nitric oxide inactivation by superoxide impairs endothelium-dependent
      vasodilation and plays a role in various forms of hypertension. Almost no data
      exist regarding hypertension secondary to chronic renal failure. Previous studies
      have shown that endothelium-related relaxations, secondary to decreased nitric
      oxide bioactivity, are impaired in resistance vessels from rats 3 to 10 days
      after renal mass reduction (RMR). METHODS: The membrane-permeable superoxide
      dismutase (SOD)-mimetic (tempol) was administered IP (1.5 mmol/kg/day for 10
      days) to RMR rats and sham-operated controls (SN). Systolic blood pressure (SBP)
      was measured by tail cuff manometry at days 0, 3, 6 and 10. The increase of flow
      induced by acetylcholine (10-6 mol/L) was measured in isolated perfused
      mesenteric arteries from RMR and SN rats pre-contracted with noradrenaline (1 to
      5 micromol/L), with or without exogenous SOD. Plasma levels of advanced oxidative
      protein products (AOPPs; chloramine-T equivalents) were measured in SN and RMR
      rats. RESULTS: Tempol prevented the increase of SBP: 118 +/- 2.2 mm Hg at
      baseline and 122 +/- 1.6 mm Hg at 10 days in tempol-treated vs 118.14 +/- 1.65 mm
      Hg at baseline and 145 +/- 7.69 mm Hg at 10 days in untreated RMR rats (P <
      0.01). Responsiveness to acetylcholine was reduced in RMR rats (peak flow
      increase: 139 +/- 7.8% vs. 176 +/- 11% in SN, P=0.028 at 3 days and 140 +/- 6.4%
      vs. 187 +/- 16.9% in SN at 10 days, P=0.007). In arteries pre-incubated with SOD
      (200 U/mL) the peak flows were 175 +/- 9.4% at 3 days and 157 +/- 5.8% at 10 days
      (P=0.007 and P=0.051, respectively, vs. control RMR vessels). AOPP values were
      significantly increased in plasma from RMR rats 3 days after 5/6 nephrectomy (747
      +/- 107 vs. 481 +/- 77 micromol/L, P < 0.05) but returned to normal by day 10.
      AOPP levels were not significantly reduced by tempol. CONCLUSIONS: Increased
      vascular superoxide production plays a central role in the development of
      vascular endothelial dysfunction and hypertension early after 5/6 nephrectomy.

PMID- 11849401
TI  - Cortical thickness: an early morphological marker of atherosclerotic renal
      disease.
AB  - BACKGROUND: Although kidney size is still the most commonly used morphological
      parameter, it is not sensitive enough for early detection of atherosclerotic
      renal disease (ARD). The purpose of this work was to evaluate morphological
      abnormalities on both post-stenotic and contralateral kidneys, by using spiral
      computed tomography angiography (CTA). METHODS: Spiral CTA was performed in 49
      hypertensive patients. Renal diameters, renal length, and cortical thickness were
      measured in 26 post-stenotic kidneys, 26 contralateral kidneys and 46 control
      kidneys. Mean cortical thickness, cortical area, and medullary length were
      calculated. RESULTS: The right and left control kidneys were of comparable
      morphology. The post-stenotic kidneys showed significant cortical atrophy. The
      contralateral kidneys also underwent cortical disease, as judged by comparison
      with control kidneys. A threshold of 800 mm2 was identified for the cortical area
      that allowed us to distinguish control kidneys from post-stenotic kidneys.
      Similarly, a threshold of 8 mm was identified for mean cortical thickness. Renal
      length was still within normal range in all kidney groups. The measurement of
      superior pole segments appeared to be more sensitive than measurement at other
      locations for identifying significant intrarenal lesions. There was no
      significant correlation between clinical and morphological parameters.
      CONCLUSIONS: These results suggest that cortical parameters are more sensitive
      for early diagnosis of ARD than kidney size. Cortical atrophy should be a useful
      marker for guidance for revascularization.

PMID- 11849402
TI  - Glucose-induced oxidative stress in mesangial cells.
AB  - BACKGROUND: Hyperglycemia is a well-recognized pathogenic factor of long-term
      complications in diabetes mellitus. Hyperglycemia not only generates reactive
      oxygen species but also attenuates antioxidant mechanisms creating a state of
      oxidative stress. METHODS: Porcine mesangial cells were cultured in high glucose
      (HG) for ten days to investigate the effects on the antioxidant defenses of the
      cell. RESULTS: Mesangial cells cultured in HG conditions had significantly
      reduced levels of glutathione (GSH) compared with those grown in normal glucose
      (NG). The reduced GSH levels were accompanied by decreased gene expression of
      both subunits of gamma-glutamylcysteine synthetase (gamma-GCS), the rate-limiting
      enzyme in de novo synthesis of GSH. Elevated levels of intracellular
      malondialdehyde (MDA) were found in cells exposed to HG conditions. HG also
      caused elevated mRNA levels of the antioxidant enzymes CuZn superoxide dismutase
      (SOD) and MnSOD. These changes were accompanied by increased mRNA levels of
      extracellular matrix proteins (ECM), fibronectin (FN) and collagen IV (CIV).
      Addition of antioxidants to high glucose caused a significant reversal of FN and
      CIV gene expression; alpha-lipoic acid also up-regulated gamma-GCS gene
      expression and restored intracellular GSH and MDA levels. CONCLUSIONS: The
      results demonstrate the existence of glucose-induced oxidative stress in
      mesangial cells as evidenced by elevated MDA and decreased GSH levels. The
      decreased levels of GSH are as a result of decreased mRNA expression of gamma-GCS
      within the cell. Antioxidants caused a significant reversal of FN and CIV gene
      expression, suggesting an etiological link between oxidative stress and increased
      ECM protein synthesis.

PMID- 11849403
TI  - Hyperhomocysteinemia predicts cardiovascular outcomes in hemodialysis patients.
AB  - BACKGROUND: We prospectively tested the prediction power of homocysteinemia for
      all-cause and cardiovascular outcomes in a cohort of 175 hemodialysis patients
      followed for 29 +/- 12 months. METHODS: Survival analysis was performed by the
      Cox's proportional hazard model and data were expressed as hazard ratio and 95%
      confidence interval (CI). RESULTS: During the follow-up period 51 patients died,
      31 of them (61%) of cardiovascular causes and 16 patients developed non-fatal
      atherothrombotic complications. Plasma total homocysteine was an independent
      predictor of cardiovascular mortality (P=0.01). Combined analysis of fatal and
      non-fatal atherothrombotic events showed that homocysteine was a strong and
      independent predictor of these outcomes because the risk of these events was 8.2
      times higher (95% CI 1.9 to 32.2) in patients in the third homocysteine tertile
      than in those in the first tertile (P=0.005). CONCLUSIONS: There is a clear
      association between hyperhomocysteinemia and incident cardiovascular mortality
      and atherothrombotic events in hemodialysis patients. Intervention studies are
      needed to determine whether the accumulation of this substance has a causal role
      in the pathogenesis of cardiovascular damage in patients undergoing hemodialysis.

PMID- 11849404
TI  - Relevance of C-reactive protein levels in peritoneal dialysis patients.
AB  - BACKGROUND: C-reactive protein (CRP) levels are increased in 30 to 50% of
      dialysis patients and predict cardiovascular morbidity and mortality. It is
      usually considered that raised CRP levels reflect underlying atherosclerosis.
      However, many patients may have clinically apparent cardiovascular disease
      without raised CRP levels. This study was designed to assess both the risk
      factors for high CRP levels and the usefulness of the test as a marker of
      clinically apparent coronary artery disease (CAD), peripheral vascular disease
      (PVD) and the presence of ongoing infections/inflammatory disorders (INF-INFL) in
      peritoneal dialysis patients. METHODS: A chart review of 190 prevalent peritoneal
      dialysis patients was performed. CRP, albumin, ferritin, erythropoietin (EPO)
      dose and resistance, Kt/V, and residual renal function values were obtained and a
      history or presence of cardiovascular disease (CAD, PVD) and presence of INF-INFL
      recorded. Data were analyzed by Chi-square, Spearman correlation and logistic
      regression. RESULTS: A total of 31% of patients had a raised CRP. INF-INFL was
      highly predictive of raised CRP levels (OR 16.97; 95% CI 5.41 to 53.14, P=0.000),
      whereas CAD and PVD either singly or in combination had no such association. The
      sensitivity/specificity for CRP as a test for INF-INFL was 83/77%. For CAD and
      PVD, the sensitivities were less than 40% and specificities 70%. Increased CRP
      values were more common in females but not in diabetics. Weak linear correlations
      existed between CRP levels and albumin, ferritin and residual renal function (r=
      0.212, 0.228 and -0.163 respectively, P < 0.02). By regression analysis, INF-INFL
      predicted high CRP levels, but CAD and PVD did not. The majority of patients
      (57%) with high CRP had no identifiable cause; 40% of these patients had
      subsequent or previous normal CRP values. High transport status predicted high
      CRP levels (OR 7.28; 95% CI 1.417 to 37.36, P=0.006). CONCLUSIONS: The majority
      of elevated CRP levels in peritoneal dialysis patients occur without an obvious
      cause. Clinically apparent cardiovascular disease does not predict high CRP
      levels. CRP levels vary over time in the same patient, from normal to high or
      vice versa, for no obvious reason. Sources of inflammation other than CAD, PVD
      and clinically obvious INF-INFL in peritoneal dialysis patients remain to be
      identified.

PMID- 11849405
TI  - Mortality and causes of death of end-stage renal disease in children: a Dutch
      cohort study.
AB  - BACKGROUND: To establish mortality rates, causes of death, and determinants of
      mortality in children with end-stage renal disease (ESRD), we performed a
      national long-term follow up study. METHODS: Mortality rate was determined in all
      Dutch patients with onset of ESRD at ages 0 to 14 years in the period between
      1972 and 1992. Causes of death and mortality determinants were investigated in
      all patients of this cohort who were born before 1979. Data were derived from the
      Dutch Registry for patients on renal replacement therapy (RRT), medical charts
      and National Health Database. RESULTS: Of all 381 patients 85 had died. The
      overall mortality rate (MR) was 1.57/100 patient-years, and the standardized
      mortality rate (SMR) was 31.0. The MR for patients 0 to 5 and 6 to 10 years old
      at onset of ESRD decreased from, respectively, 7.0 (range 0-14.9) to 3.9 (1.2
      6.7) and 4.3 (1.1-7.5) to 1.6 (0.3-2.8) between the periods 1972-1981 and 1982
      1992. The mortality hazard ratio of relatively long standing dialysis and of long
      standing hypertension were, respectively, 7.2 (4.4-11.8) and 3.1 (2.1-4.6), of
      cyclosporine-introduction in transplanted patients 0.3 (0.1-0.4). Overall
      cerebrovascular accidents (24%) and infections (21%) were the most common causes
      of death; after 10 years of RRT cardiac death (7/21) was most prevalent.
      Cardiovascular death was most prominent in dialysis as well as transplanted
      patients. CONCLUSION: Survival in children with ESRD has increased over the last
      20 years, but the SMR remains high. Early transplantation and a more vigorous
      approach toward hypertension and infection may be mandatory in order to further
      reduce mortality.

PMID- 11849406
TI  - Hypoalbuminemia and risk of death in pediatric patients with end-stage renal
      disease.
AB  - BACKGROUND: Although serum albumin is a marker for malnutrition and associated
      with a higher mortality in adult patients with end-stage renal disease (ESRD),
      the risk of death associated with serum albumin is unknown in pediatric patients
      with ESRD. We evaluated the association between serum albumin and death among
      pediatric patients initiating dialysis. METHODS: Data from the United States
      Renal Data System (USRDS) were used to identify all patients under the age of 18
      who initiated dialysis between January 1, 1995 and December 31, 1998. Using the
      Cox proportional hazards models, the association between serum albumin obtained
      45 days prior to dialysis initiation and death was estimated, controlling for
      demographic factors, dialysis modality, and anthropometric measures. RESULTS: Of
      1723 patients included in the analysis, there were 93 deaths over 2953 patient
      years of observation. The multivariate analysis demonstrated that each -1 g/dL
      difference in serum albumin between patients was associated with a 54% higher
      risk of death [adjusted relative risk (aRR), 1.54; 95% confidence interval (CI),
      1.15 to 1.85; P=0.002]. This was independent of glomerular causes for their ESRD
      and other potential confounding variables. CONCLUSIONS: Pediatric patients
      initiating dialysis with hypoalbuminemia are at a higher risk for death. This
      finding persists after adjusting for glomerular causes for ESRD and other
      potential confounding variables. Low serum albumin at dialysis initiation is an
      important marker of mortality risk in pediatric ESRD patients.

PMID- 11849407
TI  - Medial artery calcification in ESRD patients is associated with deposition of
      bone matrix proteins.
AB  - BACKGROUND: In non-ESRD patients, recent studies have demonstrated that the
      process of vascular calcification resembles developmental osteogenesis. Patients
      with ESRD are known to have excessive vascular calcification, but this has
      previously been attributed to the non-cell-mediated process of metastatic
      calcification. METHODS: To determine if the calcification observed in patients
      with ESRD is related to a cell-mediated process, we removed a piece of inferior
      epigastric artery at the time of renal transplant. Calcium content of the entire
      vessel was quantified with spiral computed tomography (CT). The vessel was then
      examined histologically for calcification and the presence of bone matrix
      proteins by immunohistochemistry, and medial and intimal thickness quantified by
      histomorphometry. These findings were correlated with demographic, clinical and
      laboratory values. RESULTS: The proximal inferior epigastric artery was obtained
      from 41 patients undergoing renal transplantation, but two were inadequate for
      histologic examination. Twenty-seven of the remaining vessels had no evidence of
      calcification by MacNeal's or Alizarin red pH 4.2 staining, five vessels had
      mild/moderate calcification, and seven had severe calcification, all in the
      medial layer. Calcification assessed histologically was closely correlated with
      calcification score as assessed by spiral CT, normalized for vessel weight
      (P=0.027). Positive immunostaining for the bone matrix proteins osteopontin, type
      I collagen, bone sialoprotein, and alkaline phosphatase was strongly correlated
      with calcification (all P < or = 0.001), as was a history of coronary artery
      disease (P < 0.001), and diabetes (P=0.034). The calcification score by spiral CT
      correlated with these same factors and the serum phosphorus and calcium x
      phosphorus product (P=0.032 and 0.037). The location of immunostaining for the
      bone proteins was strongly associated with the presence of calcification.
      However, positive immunostaining also was observed in association with
      disorganization of the vascular smooth muscle cells in the medial layer due to
      deposition of a matrix-like substance, prior to overt calcification. CONCLUSIONS:
      In patients with ESRD undergoing renal transplantation, vascular calcification of
      the medial layer of the inferior epigastric artery is common (44%), can be
      detected by spiral CT, and is associated with deposition of bone matrix proteins.
      This implies an active cell-mediated process, raising hope that directed
      intervention can arrest this process.

PMID- 11849408
TI  - Cigarette smoking and vascular pathology in renal biopsies.
AB  - BACKGROUND: In recent years cigarette smoking has been identified as a
      progression factor in chronic nephropathies such as glomerulonephritis or
      diabetic nephropathy. The exact pathomechanism of nicotine-induced renal damage
      is, however, unknown. Autopsy studies and functional investigations suggest that
      the renal vasculature is primarily affected by smoking. METHODS: Renal vascular
      pathology, that is, glomerulosclerosis, hyalinosis of arterioles and myointimal
      hyperplasia of small arteries, was determined in 135 biopsies of patients over
      thirty years of age. A questionnaire about smoking habits was returned by 107 of
      the patients. For glomerular sclerosis the percentage of sclerotic glomeruli was
      determined, whereas arteriolar hyalinosis and myointimal hyperplasia of small
      arteries were described as present or absent without further quantification. A
      univariate analysis was performed for existence of vascular changes and ever
      smoking status. In addition, a multivariate analysis for glomerular sclerosis and
      logistic regression analysis for arteriolar hyalinosis and myointimal hyperplasia
      and the variables ever-smoking, age, body mass index, creatinine clearance, blood
      pressure and lipids were performed. RESULTS: Creatinine clearance was comparable
      for nonsmokers, ex-smokers and smokers. Frequency of myointimal hyperplasia of
      small arteries was twice as high in ever-smokers as compared to nonsmokers (50%
      vs. 25.5%, P < 0.01). Arteriolar hyalinosis was detected in 23.5% of nonsmokers
      and in 35.7% of smokers, showing a trend toward hyalinosis in ever-smokers
      (P=0.20). Glomerular sclerosis was found in 62.7% of nonsmokers and in 69.6% of
      ever-smokers. Logistic regression analysis confirmed an association between ever
      smoking and myointimal hyperplasia (P < 0.01). This association also was present
      in males and patients over fifty years of age, but not in younger patients and
      females. CONCLUSION: In patients with renal, especially glomerular disease,
      cigarette smoking exhibits its deleterious effect on the kidneys primarily
      through damage of small interlobular arteries.

PMID- 11849409
TI  - Phosphate kinetics during hemodialysis: Evidence for biphasic regulation.
AB  - BACKGROUND: Hyperphosphatemia in the hemodialysis population is ubiquitous, but
      phosphate kinetics during hemodialysis is poorly understood. METHODS: Twenty-nine
      hemodialysis patients each received one long and one short dialysis, equivalent
      in terms of urea clearance. Phosphate concentrations were measured during each
      treatment and for one hour thereafter. A new model of phosphate kinetics was
      developed and implemented in VisSim. This model characterized additional
      processes involved in phosphate kinetics explaining the departure of the measured
      data from a standard two-pool model. RESULTS: Pre-dialysis phosphate
      concentrations were similar in long and short dialysis groups. Post-dialysis
      phosphate concentrations in long dialysis were higher than in short dialysis (P <
      0.02) despite removal of a greater mass of phosphate (P < 0.001). In both long
      and short dialysis serum phosphate concentrations initially fell in accordance
      with two-pool kinetics, but thereafter plateaued or increased despite continuing
      phosphate removal. Implementation of an additional regulatory mechanism such that
      a third pool liberates phosphate to maintain an intrinsic target concentration
      (1.18 +/- 0.06 mmol/L; 95% confidence intervals, CI) explained the data in 24% of
      treatments. The further addition of a fourth pool hysteresis element triggered by
      critically low phosphate levels (0.80 +/- 0.07 mmol/L, CI) yielded an excellent
      correlation with the observed data in the remaining 76% of treatments (cumulative
      standard deviation 0.027 +/- 0.004 mmol/L, CI). The critically low concentration
      correlated with pre-dialysis phosphate levels (r=0.67, P < 0.0001). CONCLUSION:
      Modeling of phosphate kinetics during hemodialysis implies regulation involving
      up to four phosphate pools. The accuracy of this model suggests that the proposed
      mechanisms have physiological validity.

PMID- 11849410
TI  - Demographic trends in the Okinawa Dialysis Study (OKIDS) registry (1971-2000).
AB  - BACKGROUND: The clinical demographics of chronic dialysis patients are changing
      worldwide. However, long-term data from regional dialysis registries have not yet
      been analyzed and reported. METHODS: The Okinawa Dialysis Study (OKIDS) registry
      included all chronic dialysis patients treated in Okinawa, Japan, since 1971.
      Data for the years 1971 to 1990 were analyzed to predict trends for 1991 to 2000.
      The predicted values were then compared to the actual values and analyzed
      statistically, with particular attention being paid to relative risk of death.
      Multivariate Cox proportional hazards analysis was done to analyze the time
      factors of relative risk of death. RESULTS: A total of 5246 patients (2981 men
      and 2265 women) were registered and the total duration of observation was 28,431
      patient-years. The prevalence and incidence of dialysis patients expressed per
      million population were 2320 and 297, respectively, in 2000, values that were
      significantly higher (P < 0.02 for both) than the predicted values. The gross
      mortality rate per 1000 patient-years was 118.4 for 1971 to 1980, 63.3 for 1981
      to 1990, and 77.7 for 1991 to 2000. The adjusted hazards ratio (95% confidence
      interval) for mortality was 0.743 (0.650 to 0.862) for 1981-1990 and 0.721 (0.659
      to 0.790) for 1991 to 2000 in comparison to the risk of mortality in 1971 to
      1980. The decrease in mortality rate was largely due to the drop in cardiac
      deaths from 71.0 for 1971 to 1980 to 17.2 for 1991 to 2000. CONCLUSIONS: The
      incidence and prevalence of chronic dialysis patients increased more than
      expected over the past decade in Okinawa, Japan. Despite the rapid change in
      patient demographics, the survival rate did not decrease significantly.

PMID- 11849411
TI  - Early application of Met-RANTES ameliorates chronic allograft nephropathy.
AB  - BACKGROUND: Initial insults to kidney allografts, characterized by infiltration
      of mononuclear inflammatory cells, contribute to chronic allograft nephropathy.
      Chemokines such as RANTES (regulated upon activation, normal T cell expressed)
      are thought to be responsible for the recruitment and activation of infiltrating
      cells. The present study investigated whether early application of Met-RANTES, a
      chemokine receptor antagonist that blocks the effects of RANTES, can protect
      renal allografts from long-term deterioration. METHODS: Fisher (F344) rat kidneys
      were orthotopically transplanted into Lewis recipients and treated with
      cyclosporine A (1.5 mg/kg/day) for the first 10 days following transplantation,
      together with either Met-RANTES at 40 microg/day, 200 microg/day or vehicle for
      the first 7 days. Animals were harvested at 2 and 28 weeks after transplantation
      for histologic, immunohistologic and molecular analysis. RESULTS: Met-RANTES
      treatment reduced the infiltration of lymphocytes and macrophages in allografts
      at 2 weeks after transplantation, accompanied by decreased mRNA expression of
      interleukin (IL)-2, IL-1beta, tumor necrosis factor-alpha (TNF-alpha) and RANTES.
      At post-transplantation week 28, Met-RANTES treatment at high and low doses
      reduced urinary protein excretion and significantly ameliorated
      glomerulosclerosis, interstitial fibrosis, tubular atrophy, intimal proliferation
      of graft arteries and mononuclear cell infiltration. However, creatinine
      clearance was not influenced by Met-RANTES. Furthermore, Met-RANTES suppressed
      the mRNA expression of transforming growth factor-beta (TGF-beta) and platelet
      derived growth factor-B (PDGF-B). CONCLUSIONS: Blockade of chemokine receptors by
      Met-RANTES diminishes early infiltration and activation of mononuclear cells in
      the grafts, and thus reduces the pace of chronic allograft nephropathy.

PMID- 11849412
TI  - Molecular and structural consequences of early renal allograft injury.
AB  - BACKGROUND: Chronic allograft nephropathy is an important cause of graft failure.
      Many donor and recipient factors contribute to its development. Prospective
      analysis of these factors has been hindered by the lack of sensitive and specific
      indicators of renal injury. As a consequence protocol biopsies have been
      increasingly used in the assessment of renal allograft injury. We performed
      protocol renal allograft biopsies to prospectively examine the role of important
      determinants and mediators of chronic allograft nephropathy. METHODS: A total of
      51 consecutive cadaveric renal transplant recipients entered a randomized
      prospective study of tacrolimus (Tac) versus cyclosporine (CsA) microemulsion
      based immunosuppression. Study patients underwent protocol renal allograft
      biopsies at the time of engraftment and at 3, 6 and 12 months post
      transplantation. Biopsies were analyzed by quantitative polymerase chain reaction
      (PCR) for mRNA for transforming growth factor-beta (TGF-beta), thrombospondin,
      and fibronectin. Measurements of renal structural injury were estimated by
      quantitative assessment of interstitial fibrosis and glomerulosclerosis. Changes
      in profibrotic growth factors and renal structural injury were related to donor
      and recipient determinants by stepwise regression analysis. RESULTS: Longitudinal
      assessment of renal injury demonstrated an early and progressive increase in mRNA
      for TGF-beta, thrombospondin (TSP) and fibronectin (FBN): TGF-beta baseline, 1.9
      +/- 0.2 log copies; TGF-beta 6 months, 2.5 +/- 0.2 log copies, P < 0.05 6 months
      vs. baseline; TSP baseline, 1.9 +/- 0.2 log copies; TSP 6 months, 2.4 +/- 0.2 log
      copies, P < 0.05 6 months vs. baseline; FBN baseline, 2.0 +/- 0.2 log copies; FBN
      12 months, 2.3 +/- 0.2 log copies, P < 0.05 12 months vs. baseline. This increase
      in profibrotic growth factors within the allograft was associated with a
      significant increase in interstitial fibrosis (Vvi) on renal biopsies: Vvi
      baseline, 13 +/- 1%; Vvi 3 months, 18 +/- 1%; Vvi 6 months, 28 +/- 2%; Vvi 12
      months, 34 +/- 2%; P < 0.05 3, 6, and 12 months vs. baseline. Histological
      analysis demonstrated chronic allograft nephropathy in 4% biopsies at 3 months,
      12% at 6 months and in 49% at 12 months. These changes in renal structure were
      not associated with any change in creatinine clearance (CCr): CCr 3 months, 56 +/
      2 mL/min, CCr 24 months, 56 +/- 2 mL/min; P=NS. Stepwise regression analysis of
      key donor and recipient determinants of chronic renal injury identified
      calcineurin inhibitors and acute rejection episodes as important factors involved
      in the development of chronic renal injury. In particular, the use of
      cyclosporine compared to tacrolimus was associated with a tenfold increase in TGF
      beta mRNA (TGF-beta mRNA at 6 months, CsA vs. Tac, 3 +/- 0.3 vs. 2 +/- 0.3 log
      copies, P < 0.05), interstitial fibrosis (Vvi at 6 months, CsA vs. Tac, 33 +/- 4%
      vs. 24 +/- 2%, P < 0.05). Changes in growth factors and renal structure predicted
      impaired renal function (CCr at 12 months, CsA vs. Tac, 53 +/- 4 mL/min vs. 62 +/
      2 mL/min, P < 0.05). Similarly, acute rejection episodes were associated with an
      accelerated development of interstitial fibrosis (Vvi at 6 months, acute
      rejection vs. no rejection, 34 +/- 3% vs. 25 +/- 2%; P < 0.05), but not with
      changes in TGF-beta, thrombospondin or fibronectin expression. CONCLUSION: Our
      results suggest that structural injury develops early in the natural history of
      the renal allograft and is mediated, in part, by the early up-regulation of
      profibrotic growth factors. We have determined that calcineurin inhibitors, in
      particular cyclosporine, and acute rejection episodes are key factors in the
      development of renal structural injury.

PMID- 11849413
TI  - Hemodynamic changes during hemodialysis: role of nitric oxide and endothelin.
AB  - BACKGROUND: Etiology of dialysis induced hypotension and hypertension remains
      speculative. There is mounting evidence that nitric oxide (NO) and endothelin (ET
      1) may play a vital role in these hemodynamic changes. We examined the
      intradialytic dynamic changes in NO and ET-1 levels and their role in the
      pathogenesis of hypotension and rebound hypertension during hemodialysis (HD).
      METHODS: The serum nitrate + nitrite (NT), fractional exhaled NO concentration
      (FENO), L-arginine (L-Arg), NGNG-dimethyl-L-arginine (ADMA) and endothelin (ET-1)
      profiles were studied in 27 end-stage renal disease (ESRD) patients on HD and 6
      matched controls. The ESRD patients were grouped according to their hemodynamic
      profile; Group I patients had stable BP throughout HD, Group II had dialysis
      induced hypotension, and Group III had intradialytic rebound hypertension.
      RESULTS: Pre-dialysis FENO was significantly lower in the dialysis patients
      compared to controls (19.3 +/- 6.3 vs. 28.6 +/- 3.4 ppb, P < 0.002). Between the
      experimental groups, pre-dialysis FENO was significantly higher in Group II (24.1
      +/- 6.7 ppb) compared to Group I (17.8 +/- 5.6 ppb) and Group III (16.1 +/- 4.2
      ppb; P < 0.05). Post-dialysis, FENO increased significantly from the pre-dialysis
      values (19.3 +/- 6.3 vs. 22.6 +/- 7.9 ppb; P=0.001). Pre-dialysis NT (34.4 +/-
      28.2 micromol/L/L) level was not significantly different from that of controls
      (30.2 +/- 12.3 micromol/L/L). Serum NT decreased from 34.4 +/- 28.2 micromol/L/L
      at initiation of dialysis to 10.0 +/- 7.4 micormol/L/L at end of dialysis (P <
      0.001). NT concentration was comparable in all the three groups at all time
      points. Pre-dialysis L-Arg (105.3 +/- 25.2 vs. 93.7 +/- 6.0 micromol/L/L; P <
      0.05) and ADMA levels were significantly higher in ESRD patients (4.0 +/- 1.8 vs.
      0.9 +/- 0.2 micromol/L/L; P < 0.001) compared to controls. Dialysis resulted in
      significant reduction in L-Arg (105.3 +/- 25.2 vs. 86.8 +/- 19.8 micromol/L/L; P
      < 0.005) and ADMA (4.0 +/- 1.8 vs. 1.6 +/- 0.7 micromol/L/L; P < 0.001)
      concentrations. Pre-dialysis ET-1 levels were significantly higher in ESRD
      patients compared to the controls (8.0 +/- 1.9 vs. 12.7 +/- 4.1 pg/mL; P <
      0.002), but were comparable in the three study groups. Post-dialysis ET-1 levels
      did not change significantly in Group I compared to pre-dialysis values (14.3 +/-
      4.3 vs.15.0 +/- 2.4 pg/mL, P=NS). However, while the ET-1 concentration decreased
      significantly in Group II (12.0 +/- 4.0 vs. 8.7 +/- 1.8 pg/mL, P < 0.05), it
      increased in Group III from pre-dialysis levels (12.8 +/- 3.8 vs. 16.7 +/- 4.5
      pg/mL, P=0.06). CONCLUSION: Pre-dialysis FENO is elevated in patients with
      dialysis-induced hypotension and may be a more reliable than NT as a marker for
      endogenous NO activity in dialysis patients. Altered NO/ET-1 balance may be
      involved in the pathogenesis of rebound hypertension and hypotension during
      dialysis.

PMID- 11849414
TI  - Plasma aminothiol oxidation in chronic hemodialysis patients.
AB  - BACKGROUND: Plasma aminothiols, including homocysteine, cysteine, and
      glutathione, function as an important extracellular redox system. We examined the
      plasma aminothiol concentration and redox status in ten chronic hemodialysis
      patients compared to ten age-matched healthy subjects. METHODS: Plasma levels of
      reduced, free oxidized, and protein-bound homocysteine, cysteine,
      cysteinylglycine, and glutathione were determined using high-pressure liquid
      chromatography (HPLC). RESULTS: Total plasma homocysteine, cysteine, and
      cysteinylglycine levels were significantly elevated in hemodialysis patients
      before dialysis compared to healthy subjects. Total plasma concentration of
      cysteine and homocysteine significantly decreased after hemodialysis. The ratio
      of free oxidized to free reduced homocysteine, cysteine, cysteinylglycine, and
      glutathione were each significantly elevated before dialysis compared to healthy
      subjects, and decreased significantly by the end of dialysis. The free oxidized
      to reduced ratio of cysteine and homocysteine were also significantly correlated
      with total plasma concentrations. CONCLUSIONS: Plasma aminothiols are excessively
      oxidized in uremia, while the hemodialysis procedure is restorative of redox
      status. Oxidized aminothiols are candidate uremic toxins.

PMID- 11849415
TI  - Pulse pressure and risk of total mortality and cardiovascular events in patients
      on chronic hemodialysis.
AB  - BACKGROUND: Pulse pressure (PP) has been shown as a risk factor for mortality or
      cardiovascular events in several studies. However, the impact of PP on prognosis
      in a cohort of chronic hemodialysis patients has not been sufficiently studied.
      We examined the effect of PP on total mortality and cardiovascular events in
      chronic hemodialysis patients, and whether PP adds useful value to systolic blood
      pressure (SBP) or diastolic blood pressure (DBP) for predicting total mortality
      and cardiovascular events in chronic hemodialysis patients. METHODS: Chronic
      hemodialysis patients (N=1243, 720 men, 523 women) alive on January 1, 1991 at
      baseline were involved in this study. Cox regression, adjusted for age, sex, and
      other risk factors, was used to assess the relation between blood pressure
      components and risk of death and cardiovascular events over a nine-year follow
      up. RESULTS: The association with the risk of total mortality was positive for PP
      (P=0.002) and SBP (P=0.04), but not significant for DBP (P=0.4), considering each
      pressure individually (single blood pressure component model, SPM); of the three
      measurements, PP yielded the highest chi2 value. When SBP and DBP were jointly
      entered into the Cox regression model (dual blood pressure component model, DPM),
      the association with the risk of total mortality was positive for SBP (HR, 1.083;
      95% CI, 1.030 to 1.137) and negative for DBP (HR, 0.886; 0.808 to 0.970). After
      the addition of diabetes mellitus as an adjusted variable to the model, PP was
      not a significant predictor for total mortality; PP was a significant predictor
      for total mortality in non-diabetic patients, but not in diabetic patients. PP
      was positively associated with the risk of stroke, and stroke and AMI; however,
      predictive value of PP for each endpoint was not superior to SBP and DBP in SPM.
      In DPM with SBP and DBP, the association with the risk of stroke and acute
      myocardial infarction (AMI) was positive for SBP (P=0.02) but not significant for
      DBP (P=0.5). In DPM with SBP and PP, the association with the risk of stroke and
      AMI was positive for SBP (P=0.01) but not significant for PP (P=0.5).
      CONCLUSIONS: In non-diabetic patients on chronic hemodialysis, PP was an
      independent predictor of total mortality. PP was more potent predictor of total
      mortality than SBP or DBP. For predicting cardiovascular events, SBP was superior
      to PP or DBP.

PMID- 11849416
TI  - Reliability of chronic allograft nephropathy diagnosis in sequential protocol
      biopsies.
AB  - BACKGROUND: Chronic allograft nephropathy (CAN) progresses rapidly during the
      first few months and slowly thereafter. Although the presence of CAN in protocol
      renal biopsies is a predictor of outcome, the reliability of this diagnosis
      according to Banff criteria has not been characterized. METHODS: Renal lesions
      were evaluated according to the Banff criteria in sequential protocol biopsies
      performed at 4 and 14 months in 310 biopsies obtained from 155 patients. RESULTS:
      CAN progressed from 40 to 53% (P=0.001) while serum creatinine remained stable
      (146 +/- 44 vs. 147 +/- 48 micromol/L, P=NS). Graft survival in patients with and
      without CAN in the first biopsy was 74 versus 91% (P < 0.05), and in the second
      biopsy 75 versus 94% (P < 0.05). In 54 patients (35%) no CAN was present in both
      biopsies, 39 (25%) showed progression to CAN, 19 (12%) showed regression of CAN,
      and 43 (28%) showed CAN in both biopsies. Graft survival was: 100%, 81.6%, 82.6%
      and 69.4%, respectively (P < 0.01). Assuming that CAN does not regress and
      sampling error is normally distributed, we estimated that 25% of biopsies cannot
      be properly classified. CONCLUSIONS: The increase in the incidence of CAN between
      the 4th and 14th month is lower than the proportion of misclassified biopsies.
      Thus, monitoring the progression of CAN by means of two sequential biopsies at 4
      and 14 months is inaccurate. We suggest that progression of scarring be monitored
      by means of a donor and a protocol biopsy performed during the first year
      evaluated with a quantitative approach.

PMID- 11849417
TI  - Peritoneal and hemodialysis: I. Differences in patient characteristics at
      initiation.
AB  - BACKGROUND: Comparisons of mortality outcomes between peritoneal dialysis (PD)
      and hemodialysis (HD) patients have shown varying results, which may be caused by
      the unequally distributed clinical conditions of patients at initiation. To
      address this issue, we evaluated the clinical characteristics of 105,954 patients
      at the initiation of PD and HD, using the U.S. national incidence data on treated
      end-stage renal disease from the Medical Evidence Form, 1995 to 1997. METHODS: A
      general linear model was used to analyze differences of age, albumin, creatinine,
      blood urea nitrogen (BUN), and hematocrit; categorical data analysis to evaluate
      body mass index (BMI), grouped into four categories: < 19, 19-25 (< 25), 25-30 (<
      30), and 30+; and logistic regression to assess the likelihood of initiating PD
      versus HD. Diabetics (DM) were analyzed separately from non-diabetics (NDM).
      Explanatory variables in the logistic regression included incidence year, race,
      gender, age, BMI, albumin, creatinine, BUN, and hematocrit. Race included white
      and black. Age was categorized into four groups: 20-44, 45-64, 65-74, and 75+.
      RESULTS: At the initiation of dialysis PD patients were approximately 6 years
      younger (P < 0.0001) than HD patients. PD patients also had higher (P < 0.0001)
      albumin (+0.35 g/dL for DM and +0.23 g/dL for NDM) and hematocrit (+1.64% for DM
      and +1.71% for NDM) levels, and lower (P < 0.04) BUN (-8.75 mg/dL for DM and 
      5.24 mg/dL for NDM) and creatinine (-0.51 mg/dL for DM and -0.23 mg/dL for NDM)
      levels than HD patients. Whites had a higher (P < 0.0001) likelihood of starting
      PD than blacks, and patients with BMI <19 had a lower (P < 0.0001) chance of
      beginning on PD. CONCLUSION: PD patients had favorable clinical conditions at the
      initiation of dialysis, which should be taken into consideration when comparing
      dialysis outcomes between the two modalities.

PMID- 11849418
TI  - Peritoneal and hemodialysis: II. Mortality risk associated with initial patient
      characteristics.
AB  - BACKGROUND: Patients initiating with peritoneal dialysis (PD) have favorable
      clinical conditions compared with hemodialysis (HD) patients, which may
      contribute to the varying results found in studies of mortality across the two
      therapies. METHODS: National incidence data of end-stage renal disease patients
      from 1995 to 1997 were used, excluding the first 90 days of treatment and
      including all patients who were on either PD or HD on day 91. Patients were then
      followed for a one-year period. A Cox proportional hazards regression analysis
      was used, separating diabetics and non-diabetics, and two statistical models were
      applied. Model 1 included race, gender, age, initial modality, and incidence year
      as explanatory variables. Model 2 added body mass index (BMI), initial levels of
      serum albumin, creatinine, and blood urea nitrogen. RESULTS: Age was most highly
      associated with mortality, followed by biochemical variables, BMI, gender, and
      dialysis modality. In diabetics, the hazard ratio (HR) from Model 1 indicated no
      difference [1.046, 95% confidence limits (CL) 0.989-1.105; P> 0.1, HD was the
      reference] in mortality between PD and HD, while Model 2 demonstrated that PD
      patients had a 13.4% (1.134, CL 1.072-1.100, P < 0.0001) higher chance of death.
      In non-diabetics, hazard ratios (HRs) from Models 1 and 2 indicated that PD
      patients had a 23.5% (0.765, 0.722-0.812, P < 0.0001) and 11.9% (0.881, 0.30
      0.935, P < 0.0001), respectively, lower likelihood of death than HD patients.
      CONCLUSION: Our study indicates that the results changed depending on the
      analytical methods used. We recommend that, due to the unequally distributed
      clinical conditions of patients at initiation, comparisons of mortality outcomes
      between dialysis modalities should be made with caution.

PMID- 11849419
TI  - Is peritoneal dialysis adequate for hypercatabolic acute renal failure in
      developing countries?
AB  - BACKGROUND: Peritoneal dialysis (PD) is a therapeutic option for acute renal
      failure (ARF) in developing countries, despite concerns about inadequacy. Shorter
      and more efficient tidal peritoneal dialysis (TPD) was compared with continuous
      equilibrating peritoneal dialysis (CEPD) therapy in ARF by using their adequacies
      as accepted standards and analyzing the solute reduction indices (SRI). METHODS:
      A prospective, randomized crossover trial was performed in patients with mild to
      moderate hypercatabolic ARF who were assigned to CEPD and TPD therapy after an
      adequate washout period. Solute clearances (Kt/V, normalized creatinine
      clearances) were compared to NKF guidelines. Potassium and phosphate clearances,
      dextrose absorption, protein losses and costs were compared. Kt/V was compared to
      SRIdialysate, SRIKt/V. RESULTS: Eighty-seven patients with ARF received 236
      sessions of dialysis (118 in each treatment). TPD resulted in higher clearances
      of solutes than CEPD (creatinine and urea clearances in mL/min of 9.94 +/- 2.93,
      6.74 +/- 1.63 and 19.85 +/- 1.95, 10.63+/- 2.62, respectively, P=0.001). TPD and
      CEPD normalized creatinine clearances (L/week/1.73 m2 BSA) and Kt/V values were
      68.5 +/- 4.43, 58.85 +/- 2.57 and 2.43 +/- 0.87, 1.80 +/- 0.32, respectively.
      CEPD did not meet standards of adequacy. TPD resulted in greater potassium and
      phosphate clearances, less dextrose absorption and was less expensive. CEPD
      resulted in less protein loss. Kt/V corresponded to SRIdialysate 0.88 +/- 0.12
      (P=0.076). CONCLUSION: TPD produced higher solute clearances in less time with
      greater protein loss. CEPD just fell short to meet the dialysis adequacy
      standard. However, both TPD and CEPD are reasonable options for mild-moderate
      hypercatabolic ARF. Kt/V appropriately estimates solute removal in PD.

PMID- 11849420
TI  - Dying neutrophils in ANCA-associated vasculitis: good or bad guys?

PMID- 11849421
TI  - Macrophage-mediated renal cell death.

PMID- 11849422
TI  - Red cell traverse through thin glomerular basement membrane.

PMID- 11849423
TI  - Acute renal failure and the sepsis syndrome.

PMID- 11849425
TI  - The complex role of nitric oxide in the regulation of glomerular ultrafiltration.
AB  - The complex role of nitric oxide in the regulation of glomerular ultrafiltration.
      Nitric oxide is an important neurohumoral modulator of glomerular ultrafiltration
      and renal hemodynamics. Multiple nitric oxide synthase (NOS) isoforms are present
      within the kidney. However, it is difficult to discern which NOS is most active
      from prior studies using non-selective NOS blockers. It is recently apparent that
      NOS activity is important to the activity of tubuloglomerular feedback (TGF)
      systems, systems that relate tubular reabsorption to the regulation of glomerular
      ultrafiltration. Neuronal (nNOS) or brain NOS (bNOS; NOS I) is present within the
      macula densa, the sensing element of TGF systems. Inhibition of NOS activity and
      specifically bNOS enhances TGF activity. The TGF system also adapts temporally
      and these events appear to be dependent upon up-regulation of activity of bNOS
      within the kidney. Temporal adaptation occurs within one to three hours whereby
      activation of TGF is followed by a gradual return of the glomerular filtration
      rate (GFR) and renal blood flow toward normal levels. After 24 hours of
      benzolamide treatment and withdrawal of this agent, glomerular filtration
      actually increases to supranormal levels and this is prevented by inhibition of
      bNOS activity. Factors regulating bNOS activity have not been fully clarified. We
      have recently observed N-methyl-d-aspartate (NMDA) receptors within the kidney
      that, when inhibited, result in major reductions in renal blood flow and GFR,
      suggesting an important role for the NMDA receptor in regulation of renal
      hemodynamics. Future studies will determine whether NMDA receptor is also an
      important regulator of bNOS activity and the TGF system.

PMID- 11849426
TI  - Nitric oxide and apoptosis in mesangial cells.
AB  - Nitric oxide and apoptosis in mesangial cells. Radicals such as nitric oxide (NO)
      or superoxide (O(-)(2)) encompass the ability to initiate morphological and
      biochemical alterations that are reminiscent of apoptosis. In mesangial cells,
      death as a result of NO formation is efficiently antagonized by the simultaneous
      presence of superoxide (O(-)(2)) and vice versa. This article reviews the
      consequences of a diffusion controlled NO/O(-)(2) interaction with the outcome of
      redirecting the apoptotic initiating activity of either NO or O(-)(2) toward
      protection. The crosstalk between cell destructive and protective pathways, and
      their activation or inhibition under the modulatory influence of NO and/or O(
      )(2) are summarized.

PMID- 11849428
TI  - Cyclic AMP increases rat inhibitor of apoptosis protein (RIAP1) mRNA in renal
      mesangial cells.
AB  - BACKGROUND: The cyclic adenosine 3',5'-monophosphate (cAMP) pathway plays a
      central role in the regulation of cell proliferation, differentiation and
      apoptosis. Cyclic AMP has been identified as a bifunctional regulator of
      apoptosis. The inhibitor of apoptosis proteins (IAP) regulates apoptosis by
      directly inhibiting distinct caspases. METHODS: Expression levels of rat IAP
      (RIAP)-1 were investigated by RNase protection assay in rat mesangial cells after
      stimulation with diverse agents that modulate cellular levels of cAMP. RESULTS:
      Rat mesangial cells up-regulated RIAP1 mRNA levels after cAMP stimulation.
      Membrane-permeable cAMP analogs, as well as cAMP production in response to the
      beta-adrenergic receptor agonist salbutamol caused a large increase in RIAP1 mRNA
      level, which could be inhibited by the protein kinase A inhibitors H89 and Rp
      cAMPS, or by the nuclear factor-kappaB (NF-kappaB) inhibitor BAY117085.
      Inhibition of phosphodiesterase type IV by denbufyllin or rolipram potentiated
      the cAMP-mediated increase in RIAP1 mRNA. In contrast, the cyclic guanosine 3',5'
      monophosphate (cGMP) analog Bt2cGMP did not affect the RIAP1 mRNA level.
      CONCLUSIONS: These data establish, to our knowledge for the first time, that
      RIAP1 mRNA levels are regulated by the cAMP-signaling pathway and suggest
      potential new avenues of therapy to modulate apoptosis.

PMID- 11849427
TI  - Cross-talk between nitric oxide and superoxide determines ceramide formation and
      apoptosis in glomerular cells.
AB  - BACKGROUND: The modulation of cell signaling by nitric oxide (NO) and superoxide
      (O(-)(2)) is associated with apoptotic cell death in inflammatory kidney
      diseases. Recently, we have shown that NO induces ceramide production in
      glomerular mesangial and endothelial cells and the ratio of NO and O(-)(2)
      determines whether cells live or die. METHODS: Glomerular endothelial and
      mesangial cells were labeled with [(14)C]serine, the precursor of all
      sphingolipids, then stimulated with reactive oxygen species- or reactive nitrogen
      species-generating substances and subjected to lipid extraction. Radioactive
      lipids were separated and analyzed by thin-layer chromatography. DNA
      fragmentation, as a characteristic feature of apoptosis, was measured by a
      nucleosome/DNA-ELISA, which quantitatively recorded the histone-associated DNA
      fragments. RESULTS: Exposure of glomerular endothelial and mesangial cells to
      either NO donors or superoxide-generating substances led to a delayed and
      sustained ceramide formation that paralleled the induction of apoptosis in both
      cell types. Coincubation of endothelial cells with NO and superoxide, which led
      to the generation of peroxynitrite, caused a synergistic enhancement of ceramide
      generation and apoptosis when compared to either stimulus alone. By contrast, in
      glomerular mesangial cells costimulation with superoxide neutralized not only NO
      induced apoptosis but also NO-induced ceramide formation, although O(-)(2) alone
      triggered ceramide formation in mesangial cells and caused cell death. Moreover,
      SIN-1, a substance that simultaneously releases NO and O(-)(2) and thereby
      generates peroxynitrite, also stimulated a delayed ceramide formation in
      endothelial cells but not in mesangial cells. Furthermore, exposure of
      endothelial cells to glucose oxidase, which generates hydrogen peroxide, or to
      exogenous hydrogen peroxide, also showed a dose-dependent increase in ceramide
      formation and apoptosis, although to a lesser extent than did superoxide.
      CONCLUSIONS: These data suggest that ceramide represents an important mediator of
      reactive oxygen and nitrogen species-triggered cell responses, like apoptosis.
      There seem to be cell type-specific protective mechanisms that critically depend
      on a fine-tuned redox balance between reactive nitrogen and oxygen species to
      determine whether a cell undergoes apoptosis or survives when exposed to
      oxidative and/or nitrosative stress conditions.

PMID- 11849429
TI  - Nitric oxide regulates matrix metalloprotease-13 expression and activity in
      endothelium.
AB  - BACKGROUND: Matrix metalloproteinases (MMPs) are synthesized in response to
      diverse stimuli including cytokines, growth factors, hormones, and oxidative
      stress. METHODS: Bovine aortic endothelial cells (BAEC) were stimulated with
      nitric oxide (NO) and MMP-13 expression and activity was assayed. RESULTS: NO
      transcriptionally regulated matrix metalloproteinase-13 (MMP-13) expression in
      BAEC, while the cGMP analog 8Br-cGMP mimicked the effect of NO. In addition NO
      also stimulated the proteolytic processing of MMP-13 from the pro-enzyme to the
      final active form in a dose dependent manner. CONCLUSION: NO transcriptionally
      regulates MMP expression and activity in the vascular endothelium. This effect of
      NO may be of pathophysiological importance in the context of angiogenesis,
      inflammation or atherogenesis.

PMID- 11849430
TI  - Changing gears in the course of glomerulonephritis by shifting superoxide to
      nitric oxide-dominated chemistry.
AB  - The glomerular response to injury displays astonishingly uniform features that
      include infiltration with professional immune cells, activation and proliferation
      of resident glomerular cells and matrix expansion. Cross-communication of
      intrinsic mesangial cells with invading immune cells is crucial for the fate of
      glomerular injury: progression to glomerulosclerosis or resolution and repair.
      The formation of free radicals, particularly of nitric oxide and superoxide, are
      key events that initiate redox-based signal transduction and gene expression. The
      balance between these radicals constitutes redox-operated genetic switches that
      ensure self-limited inflammatory responses to tissue injury. The aberrant
      production of the mediators, however, may sustain matrix accumulation and result
      in irreversible alteration of glomerular structure and function.

PMID- 11849431
TI  - Nitric oxide and glomerulonephritis.
AB  - The glomerulus is a unique vascular network with the potential to express several
      isoforms of nitric oxide synthase (NOS). Induction of inducible NOS (iNOS) occurs
      as part of a rapid initial response to immune injury in glomerulonephritis (GN).
      Studies on rodent models suggest that this is due to activation of transcription
      factors by reactive oxygen species (ROS), generated in responses to Fcgamma and
      CR engagement. iNOS operates in a complex milieu among multiple other
      inflammatory mediators, changing expression of constitutive NOS (endothelial NOS,
      eNOS), a critical regulator of glomerular function, and auto-regulating its own
      expression. As yet there is no consensus as to the role of high output NO
      generated by iNOS in the glomerulus, although many studies have demonstrated that
      NO inhibition can alter the level of proteinuria and leukocyte infiltration, and
      other manifestations of injury such as thrombosis, proliferation, and matrix
      production. This article reviews the evidence accumulated from experimental
      studies over the past decade, and discusses how these conflicting data can be
      reconciled to form a working hypothesis on the role of NO in GN.

PMID- 11849432
TI  - A protective role for endothelial nitric oxide synthase in glomerulonephritis.
AB  - In acute glomerulonephritis (GN), increased nitric oxide (NO) production occurs,
      suggesting a pathophysiological role for NO in the disease process. Although NO
      potentially could have both toxic as well as protective effects, its exact role
      in the pathophysiology of GN is unclear and may depend on the NOS isoform
      generating NO. The protective effects of NO such as prevention of leukocyte and
      platelet activation and adhesion have been attributed to NO generated by
      endothelial nitric oxide synthase (eNOS). Evidence for a beneficial role for eNOS
      includes the demonstration of reduced eNOS expression in experimental models of
      GN as well as human biopsy specimens that is mostly likely due to endothelial
      cell necrosis. Reduced NO production in GN also may occur through reaction of NO
      with superoxide anions or the myeloperoxidase (MPO)/hypochlorous acid (HOCL)
      system. Further evidence has been provided by the observation that in several
      experimental models of GN, glomerular injury is exacerbated following treatment
      with non-selective NO inhibitors. Finally, the development of GN is severely
      aggravated in mice lacking a functional gene for eNOS as compared to wild-type
      mice, providing direct support for a protective role of eNOS-derived NO in acute
      GN.

PMID- 11849433
TI  - Nitric oxide synthase isoform expression in acute versus chronic anti-Thy 1
      nephritis.
AB  - BACKGROUND: Two inbred Lewis rat substrains (LEW/Moe, LEW/Maa) were identified
      responding differently to induction of anti-Thy 1 glomerulonephritis (aThy 1-GN).
      LEW/Moe rats show an acute mesangioproliferative glomerulonephritis with rapid
      healing of glomerular lesions within four weeks, while LEW/Maa rats develop
      severe glomerular injury followed by chronic glomerular sclerosis and persistent
      albuminuria. We investigated whether the glomerular expression pattern of nitric
      oxide synthase (NOS) isoforms could explain these substrain-related differences.
      METHODS: Rats (N = 5 to 7 per group) were investigated in a time course
      experiment. Severity of aThy 1-GN was determined by albuminuria measurements,
      glomerular matrix score and microaneurysm formation. Glomerular gene expression
      of NOS isoforms was determined by semiquantitative RT-PCR. Inducible NOS (iNOS)
      activity was determined in cultured glomeruli and peritoneal macrophages.
      Neuronal NOS (nNOS) protein expression was detected by Western blotting and
      enzyme histochemistry. Plasma renin activity (PRA) was measured by RIA. RESULTS:
      Induction of iNOS expression and activity was found significantly increased and
      sustained in LEW/Maa vs. LEW/Moe rats associated with an increased number of
      infiltrating macrophages and with an increased capacity of iNOS-expression and
      iNOS-activation by isolated macrophages in LEW/Maa rats. Glomerular nNOS mRNA and
      nNOS protein expression were constitutively increased in LEW/Maa rats. Renal nNOS
      localization was restricted to the macula densa region in both substrains and
      associated with increased PRA in LEW/Maa rats. No difference in glomerular
      endothelial NOS-mRNA expression between the substrains was observed. CONCLUSIONS:
      Increased glomerular iNOS and nNOS expression were associated with chronic anti
      Thy 1 glomerulonephritis in LEW/Maa rats and may contribute to glomerular damage
      by separate mechanisms.

PMID- 11849434
TI  - Selective inhibition of inducible nitric oxide synthase enhances intraglomerular
      coagulation in chronic anti-Thy 1 nephritis.
AB  - BACKGROUND: A particular Lewis rat substrain (LEW/Maa) develops chronic
      glomerulonephritis in the anti-Thy 1 model (aThy 1-GN) characterized by increased
      microaneurysm formation, chronic glomerular sclerosis and persistent albuminuria.
      This phenotype is accompanied by increased and prolonged glomerular induction of
      inducible nitric oxide synthase (iNOS) when compared to the LEW/Moe substrain, in
      which aThy 1-GN resolves quickly. We investigated the effect of selective iNOS
      inhibition by l-N6-(1-iminoethyl)-lysine (L-NIL) administration on aThy 1-GN in
      LEW/Maa rats. METHODS: Nephritic rats were studied over a period of 7 days. L-NIL
      treated animals received 20 mg/day L-NIL in the drinking water starting two days
      prior to disease induction. iNOS activity was determined in cultured glomeruli
      and in urine samples, respectively. Severity of aThy 1-GN was determined by
      scoring glomerular matrix expansion and microaneurysm formation, and by
      albuminuria measurements (ELISA). Immunohistochemical evaluation was performed
      including staining for macrophages (ED-1), platelets (PL-1) and fibrin
      deposition. RESULTS: L-NIL treated rats (+NIL) showed a significant decrease in
      peak nitrate production by ex vivo cultured glomeruli, and in urinary nitrate
      excretion versus untreated nephritic rats (-NIL). Mean arterial pressure remained
      unchanged in both +NIL and -NIL rats. +NIL rats developed significantly increased
      albuminuria (+44%) associated with a significant increase in glomerular platelet
      (+45%) and fibrin deposition (+48%). CONCLUSIONS: Selective inhibition of iNOS
      aggravated albuminuria in chronic aThy 1-GN in LEW/Maa rats. Induction of iNOS
      during the inflammatory phase of this model may be a partially protective
      mechanism by interfering with intraglomerular coagulation processes.

PMID- 11849435
TI  - Modulation of renal disease in MRL/lpr mice by pharmacologic inhibition of
      inducible nitric oxide synthase.
AB  - BACKGROUND: MRL-MPJFaslpr (MRL/lpr) mice spontaneously develop lupus-like disease
      characterized by immune complex glomerulonephritis and overproduction of nitric
      oxide (NO). Blocking NO production pharmacologically by a non-specific nitric
      oxide synthase (NOS) inhibitor ameliorated renal disease in MRL/lpr mice while
      genetically deficient inducible NOS (iNOS) mice developed proliferative
      glomerulonephritis similar to wild-type controls. METHODS: To clarify the role of
      iNOS in the pathogenesis of nephritis in MRL/lpr mice, we treated mice with two
      different NOS inhibitors. Either NG-monomethyl-l-arginine (L-NMMA), a nonspecific
      NOS inhibitor, or l-N6-(1-iminoethyl)lysine (L-NIL), an iNOS specific inhibitor,
      was administered in the drinking water from 10 through 22 weeks of age with
      disease progression monitored over time. Control mice received water alone.
      RESULTS: Both L-NMMA and L-NIL blocked NO production effectively in MRL/lpr mice.
      As expected, neither L-NNMA nor L-NIL had an effect on antibody production,
      immune complex deposition or complement activation. Although both NOS inhibitors
      decreased protein excretion, L-NMMA was more effective than L-NIL. Pathologic
      renal disease was significantly decreased at 19 weeks in both treatment groups.
      At 22 weeks the L-NIL treated mice, but not the L-NMMA mice, had significantly
      reduced renal disease scores compared to controls. CONCLUSION: These results
      indicate that specific inhibition of iNOS blocks the development of pathologic
      renal disease in MRL/lpr mice.

PMID- 11849436
TI  - Interactions between inducible nitric oxide synthase and heme oxygenase-1 in
      glomerulonephritis.
AB  - BACKGROUND: In anti-glomerular basement membrane (GBM) nephritis, inducible
      nitric oxide synthase (iNOS) and heme oxygenase (HO-1) are co-induced. Moreover,
      in glomerular mesangial cells iNOS-derived nitric oxide (NO) production
      stimulates HO-1 while HO-1 activation reduces iNOS expression/activity. These
      observations prompted us to explore regulatory interactions between iNOS and HO-1
      in anti-GBM nephritis. METHODS: Rats with anti-GBM nephritis were pretreated with
      the iNOS inhibitor l-N6-(1-iminoethyl) lysine (L-NIL) or with the HO-1 inducer
      hemin. Glomerular HO-1 levels were assessed by Western blot analysis. iNOS
      activity was assessed by calculating conversion of l-arginine to l-citrulline.
      RESULTS: iNOS inhibition reduced glomerular HO-1 levels without altering the
      inflammatory response to anti-GBM antibody induced injury. Induction of HO-1
      reduced glomerular iNOS activity. CONCLUSIONS: In anti-GBM nephritis iNOS up
      regulates HO-1 presumably via high output NO production. Suprainduction of HO-1
      attenuates iNOS activity. This negative feedback interaction points to HO-1 as a
      target for pharmacologic manipulation to reduce activity of prooxidant heme
      containing enzymes such as iNOS.

PMID- 11849437
TI  - Effect of acute iNOS inhibition on glomerular function in tubulointerstitial
      nephritis.
AB  - BACKGROUND: Tubulointerstitial nephritis (TIN) is characterized by progressive
      inflammatory infiltrate of the renal interstitium, induction of cortical tubular
      inducible nitric oxide synthase (iNOS) and reductions in glomerular filtration
      rate (GFR). These studies were designed to examine the changes in glomerular
      hemodynamics 7 and 21 days after induction of TIN and to evaluate the effect of
      acute iNOS blockade on glomerular function in the early stages of this model.
      METHODS: TIN was induced by immunizing Brown Norway rats with renal tubular
      antigen in complete Freund's adjuvant (RTA/CFA). Control rats were immunized with
      CFA alone. Micropuncture and morphologic studies were performed 7 and 21 days
      after immunization. RESULTS: Histology revealed minimal peritubular and
      interstitial inflammation in the RTA/CFA group one week after immunization while
      extensive interstitial inflammation with few preserved superficial nephron was
      observed three weeks after RTA/CFA immunization. Micropuncture studies on day 7
      in the RTA/CFA group revealed a significant reduction in single nephron GFR due
      to a profound reduction in nephron plasma flow and in the ultrafiltration
      coefficient. Studies performed on day 21 revealed that single nephron GFR
      (SNGFR), nephron plasma flow (SNPF) and the ultrafiltration coefficient had
      returned to the normal baseline value despite the severe reduction in GFR. To
      assess the role of increased nitric oxide production secondary to iNOS induction
      on the glomerular hemodynamic changes observed in the early stages of the
      disease, the iNOS blocker (l-N(6)-iminoethyl lysine, L-NIL) was administered IV
      (1 mg/h) in RTA/CFA rats and CFA rats. L-NIL had no effect in CFA rats but
      produced significant increases in GFR, SNGFR and SNPF in RTA/CFA rats.
      CONCLUSIONS: These results demonstrate that TIN is associated with a progressive
      reduction in GFR, which is likely the result of functional vasoconstriction and
      decreases in the ultrafiltration coefficient in the early stages of the disease
      and on a significant reduction in the number of functioning nephron in the later
      stages. Induction of iNOS with increased NO production actively participates in
      the functional changes observed in the early stages of the disease most likely by
      inhibiting normal endothelial NOS activity.

PMID- 11849439
TI  - Inhibition of inducible nitric oxide synthase reduces renal ischemia/reperfusion
      injury.
AB  - BACKGROUND: Nitric oxide (NO), produced via inducible nitric oxide synthase
      (iNOS), is implicated in the pathophysiology of renal ischemia/reperfusion (I/R)
      injury. The aim of this study was to investigate the effects of the iNOS
      inhibitors L-N6-(1-iminoethyl)lysine (L-NIL) and aminoethyl-isothiourea (AE-ITU)
      on (a) renal dysfunction and injury mediated by bilateral I/R of rat kidneys in
      vivo and (b) cytokine-stimulated NO production by primary cultures of rat
      proximal tubule (PT) cells. METHODS: Male Wistar rats subjected to bilateral
      renal ischemia (45 min) followed by reperfusion (6 h). Rats were administered
      either L-NIL (3 mg/kg IV bolus 15 min prior to I/R followed by 1 mg/kg/h
      throughout I/R) or AE-ITU (1 mg/kg IV bolus 15 min prior to I/R followed by 1
      mg/kg/h throughout I/R). Serum and urinary biochemical indicators of renal
      dysfunction and injury were measured; serum creatinine (SCr, glomerular
      dysfunction), fractional excretion of Na+ (FENa, tubular dysfunction), serum
      aspartate aminotransferase (sAST, I/R injury) and urinary N-acetyl-beta-d
      glucosaminidase (uNAG, tubular injury). Additionally, renal sections were used
      for histological grading of renal injury and for immunological evidence of
      nitrotyrosine formation. Nitrate/nitrate levels in plasma were measured using the
      Griess assay and used as an indicator of NO production. Primary cultures of rat
      PT cells were incubated with interferon-gamma(IFN-gamma, 100 IU/mL) and
      lipopolysaccharide (LPS, 10 microg/mL) for 24 h, either in the absence or
      presence of increasing concentrations of L-NIL or AE-ITU (0.001 to 1 mmol/L)
      after which nitrite/nitrate levels were measured using the Griess assay. RESULTS:
      L-NIL and AE-ITU significantly reduced the I/R-mediated increases in SCr, FENa,
      sAST and uNAG, indicating attenuation of I/R-mediated renal dysfunction and
      injury. Specifically, L-NIL and AE-ITU reduced the I/R-mediated glomerular and
      tubular dysfunction and biochemical and histological evidence of tubular injury.
      Both L-NIL and AE-ITU attenuated the plasma levels of nitrate (indicating reduced
      NO production) and the immunohistochemical evidence of the formation of
      nitrotyrosine. In vitro, L-NIL and AE-ITU both significantly reduced cytokine
      stimulated NO production by primary cultures of rat PT cells in a dose-dependent
      manner. CONCLUSIONS: These results suggest that L-NIL and AE-ITU reduce the renal
      dysfunction and injury associated with I/R of the kidney, via inhibition of iNOS
      activity and subsequent reduction of NO (and peroxynitrite) generation. We
      propose that selective and specific inhibitors of iNOS activity may be useful
      against the NO-mediated renal dysfunction and injury associated with I/R of the
      kidney.

PMID- 11849440
TI  - Inducible nitric oxide synthase in renal transplantation.
AB  - The importance of the endothelial isoform of nitric oxide synthase (eNOS) has
      been well established. Endothelium-derived nitric oxide has been shown to be
      essential for vascular homeostasis and modulation of eNOS has thus become a
      target in prevention of cardiovascular disease. The role of the inducible form of
      nitric oxide synthase (iNOS) in vascular biology, however, is less clear.
      Classically, iNOS has been regarded as an enzyme that produces nmolar amounts of
      the nitric oxide radical, thereby leading to cellular damage. More recent data,
      however, have shown that the iNOS can be a superoxide, peroxynitrite as well as a
      nitric oxide-producing enzyme, while the biological effects of iNOS probably
      depend upon the sort of radical species released by the enzyme as well as the
      anti-oxidant capacity of the cellular microenvironment of the enzyme. This brief
      review discusses these aspects in relation to renal transplantation.

PMID- 11849438
TI  - Nitric oxide in acute renal failure: NOS versus NOS.
AB  - This overview provides information on the pathophysiology of the inducible nitric
      oxide synthase/nitric oxide (iNOS/NO) system in the injury to cultured renal
      tubular epithelia, freshly isolated proximal tubules, and the whole organ after
      hypoxic or ischemic insult. The findings emphasize the role of concomitant
      oxidative and nitrosative stress and the role of peroxynitrite in the ensuing
      renal dysfunction. Scavenging peroxynitrite using seleno-organic compounds like
      ebselen provides renoprotection against ischemic injury. These sequelae of renal
      ischemia are a result of endothelial dysfunction, which is most probably
      responsible for the "no-reflow" phenomenon and further aggravation of tubular
      ischemia during the early reperfusion period. Recent studies have demonstrated
      that transplantation of functional endothelial cells into ischemic kidney
      provided a dramatic renoprotective effect. In conclusion, the intricate relations
      between endothelial and epithelial cells, based in part on the relations between
      endothelial and inducible nitric oxide synthases, are perturbed in renal ischemia
      primarily as a result of endothelial dysfunction precipitating epithelial injury.

PMID- 11849441
TI  - Arginase in glomerulonephritis.
AB  - l-Arginine is converted to nitric oxide and citrulline by the enzyme nitric oxide
      synthase (NOS). Its in vivo inhibition has led to the revelation of a multitude
      of diverse, often conflicting functions in the inflammatory melee. l-Arginine is
      also converted to ornithine and urea by the enzyme arginase as a part of the
      hepatic urea cycle. However, a more holistic interpretation of the two pathways
      and the associated metabolism (summarized in Fig. 1) has led to its reassessment
      as a pathologically significant enzyme. This is reflected by the continued
      increase over the past five years of the number of publications discussing both
      nitric oxide and arginase. The strong association between inflammation and high
      arginase and NOS activity is epitomized by immune complex-induced
      glomerulonephritis and other glomerulonephritides. Arginase is encoded by two
      recently discovered genes (Arginase I and Arginase II). There is now substantial
      evidence for an interaction between both arginase isoforms and all three NOS
      isoforms in pathological situations. This review considers the relationship
      between Arginases I and II and the inflammation-associated isoform of NOS called
      NOS II. In particular, it consolidates the current understanding of arginase and
      associated metabolic pathways, and highlights some of the issues that are often
      overlooked in such studies.

PMID- 11849442
TI  - Nitric oxide drives skin repair: novel functions of an established mediator.
AB  - Wound healing of the skin represents a highly ordered process of important tissue
      movements that aims for a rapid closure of the wound site and a subsequent
      regeneration of the injured tissue. The factors ensuring the intercellular
      communication during repair are only known in part. However, although protein
      type mediators are well-established players in this process, it has become
      evident that the diffusible, gaseous molecule nitric oxide (NO) participates in
      the orchestration of wound healing. The role of wound-derived NO that critically
      influences macrophage, fibroblast, and keratinocyte behaviour within the
      intercellular communication network during repair is subject of this review.
      Thus, cutaneous wound healing prototypically reflects processes that generally
      occur also in kidney injury and regeneration.

PMID- 11849443
TI  - Paradigm shift from classic anatomic theories to contemporary cell biological
      views of CAKUT.
AB  - Ectopic budding of the ureter from the Wolffian duct is the first ontogenic
      misstep that leads to many-if not all-congenital anomalies of the kidney and
      urinary tract (CAKUT). The ectopia results in hypoplastic kidney, ectopia of
      ureterovesical orifice, urinary outflow obstruction and/or reflux. Studies in
      several mutant mouse models have verified that ectopic ureteric budding indeed
      precedes formation of CAKUT. Often, the genes involved in navigating ureteric
      budding to the correct site also regulate later ontogenic events of the kidney
      and urinary tract. The wide spectrum of CAKUT, for example, multicystic
      dysplastic kidney, megaureter and atretic ureter, portray the additional
      important functions of these same genes that are activated at multiple sites and
      stages during the normal morphogenesis of the kidney and urinary tract

PMID- 11849444
TI  - Expression of mitogen-activated protein kinases in human renal dysplasia.
AB  - BACKGROUND: We previously reported that the expression of mitogen-activated
      protein kinases (MAPKs) is developmentally regulated. Dysregulation of MAPKs may
      lead to kidney malformation. Thus, we investigated the expression of MAPKs in
      human renal dysplasia, one of the most common kidney malformations. METHODS:
      Prenatal (gestational ages 20 to 36 weeks, N = 6) and postnatal (2 years old, N =
      1) dysplastic kidneys, and normal kidneys (gestational ages 19 to 34 weeks, N =
      4) were examined. Immunohistochemical studies were performed using antibodies
      against extracellular signal-regulated kinase (ERK), p38 MAPK (p38), c-Jun N
      terminal kinase (JNK), phospho-MAPKs (P-MAPKs), and proliferating cell nuclear
      antigen (PCNA). Apoptosis was detected by the TUNEL method. RESULTS: In
      dysplastic kidneys, proliferation was prominent in dysplastic tubules and also
      found in cyst epithelia. TUNEL staining was detected in dysplastic tubules and
      cysts, and occasionally in undifferentiated cells. p38 and anti-phospho-p38 (P
      p38) were strongly expressed in dysplastic epithelia, but not detected in normal
      kidneys at any stage examined. On the other hand, JNK and P-JNK were positive in
      tubular epithelia of normal kidneys, whereas their expression was barely
      detectable in dysplastic tubules and cysts. ERK was expressed in all tubular
      segments, and P-ERK was detected in distal tubules and collecting ducts of normal
      kidneys. Dysplastic kidney epithelia stained exclusively positive for ERK and P
      ERK. CONCLUSIONS: p38 is ectopically expressed, and JNK is down-regulated in
      dysplastic kidney epithelia. Furthermore, dysplastic epithelia are exclusively
      positive for ERK and P-ERK. Activated p38 and ERK may mediate hyperproliferation
      of dysplastic tubules resulting in cyst formation, whereas down-regulated JNK
      expression may be the cause or the result of an undifferentiated state of
      dysplastic epithelia.

PMID- 11849445
TI  - Hereditary renal amyloidosis caused by a new variant lysozyme W64R in a French
      family.
AB  - BACKGROUND: The number of proteins with mutations resulting in amyloidosis has
      continued to increase. Five proteins--transthyretin, fibrinogen alpha-A chain,
      apolipoprotein AI, lysozyme, apolipoprotein AII, cystatin C and gelsolin--can be
      associated with hereditary amyloidosis involving the kidney. METHODS: A French
      family with a history of autosomal dominant hereditary amyloidosis with early
      sicca syndrome and nephropathy leading to renal failure after the fifth to the
      seventh decade was studied. Several tissue specimens obtained from the proband
      and his relatives were examined. Immunohistochemistry was performed on paraffin
      embedded sections using the indirect immunoperoxidase technique. We searched for
      mutations in the five exons and flanking introns of the lysozyme gene. RESULTS:
      Amyloid deposits from the bowel, labial salivary gland and kidney were
      intensively stained by anti-lysozyme antibody. Sequence analysis of lysozyme exon
      2 from the affected individuals revealed a nucleotide substitution predicting a
      substitution of the amino acid at position 64 in the mature protein from
      tryptophane, an aromatic residue to the cationic residue arginine (W64R).
      CONCLUSION: We report a novel mutation (W64R) of the lysozyme that is associated
      with hereditary amyloidosis and prominent nephropathy. Since the treatment of
      hereditary amyloidosis greatly varies with the nature of the amyloid protein,
      thorough characterization of the latter is crucial for the management of the
      disease.

PMID- 11849446
TI  - High glucose down-regulates angiotensin II binding via the PKC-MAPK-cPLA2 signal
      cascade in renal proximal tubule cells.
AB  - BACKGROUND: It has been reported that renal renin-angiotensin system contributes
      to the development of diabetic nephropathy. However, the mechanism of angiotensin
      II receptor regulation in diabetic condition has not been elucidated. METHODS:
      The effects of high glucose on [(3)H]-arachidonic acid (AA) release and
      angiotensin II (Ang II) binding and its related signal pathway were examined in
      primary cultured rabbit renal proximal tubule cells (PTCs). RESULTS: High glucose
      down-regulated (125)I-Ang II binding from 12 hours and this response was
      sustained over 48 hours. Thus, the treatment of 25 mmol/L glucose for 48 hours
      was used for this study. High glucose-induced down-regulation of (125)I-Ang II
      binding was reversed by the removal of extracellular glucose, suggesting a role
      for glucose specificity. The high glucose-induced down-regulation of (125)I-Ang
      II binding was blocked by mepacrine, AACOCF3, phospholipase A2 inhibitors,
      indomethacin, ibuprofen, and cyclooxygenase inhibitors. Indeed, high glucose
      significantly increased prostaglandin E2 synthesis. In addition, the high glucose
      induced AA release was blocked by PD 98059, a p44/42 mitogen-activated protein
      kinase (MAPK) inhibitor. PD 98059 also prevented the down-regulation of (125)I
      Ang II binding by high glucose, suggesting a role for p44/42 MAPK. Indeed, high
      glucose significantly increased p44/42 MAPK activity after the 15-minute time
      point. Protein kinase C (PKC) inhibitor blocked high glucose-induced activation
      of p44/42 MAPK, increase of the [(3)H]-AA release, and down-regulation of 125I
      Ang II binding. W-7 and KN-62 also blocked the high glucose-induced increase of
      [(3)H]-AA release and down-regulation of (125)I-Ang II binding. However,
      phospholipase A2 inhibitor did not block high glucose-induced activation of
      p44/42 MAPK. CONCLUSION: High glucose down-regulates (125)I-Ang II binding via
      the PKC-MAPK-cPLA2 signal pathway.

PMID- 11849447
TI  - STAT3, but not ERKs, mediates the IL-6-induced proliferation of renal cancer
      cells, ACHN and 769P.
AB  - BACKGROUND: Although interleukin-6 (IL-6) has been suggested to function as an
      autocrine growth factor in renal cell carcinoma (RCC), the underlying mechanism
      responsible for the IL-6-induced proliferation of RCC has not been defined. The
      aim of this study was to characterize the signaling cascades mediating IL-6
      induced proliferation and to investigate the use of effective novel interventions
      to block the IL-6-induced autocrine growth of renal cancer cells. METHODS: IL-6
      induced proliferation and intracellular signaling cascades were analyzed in four
      human renal cancer cell lines Caki-1, ACHN, 769P and A498. IL-6-induced
      activation of STAT3 (signal transducer and activator of transcription-1) and
      extracellular signal-regulated kinases (ERKs), and the effects of anti-IL-6
      neutralizing antibody, Jak inhibitor AG 490, and MEK1 inhibitor PD 98059 were
      analyzed by Western blotting using phospho-specific antibodies. The DNA-binding
      activities of STATs were analyzed by EMSA. Apoptosis was determined by using
      nuclear staining and the TUNEL assay. Changes in the apoptosis-related proteins,
      bcl-2, bcl-xL, and bax were analyzed by Western blotting. RESULTS: IL-6 induced
      tyrosine phosphorylation and increased the DNA binding activity of STAT3 and, to
      a lesser extent, STAT1 in all cell lines except for Caki-1, which did not express
      the IL-6 receptor subunit gp130. ERKs were constitutively activated in all cell
      lines and the activation level was not up-regulated further by exogenously added
      IL-6 nor down-regulated by anti-IL-6 neutralizing antibody. IL-6-induced STAT3
      tyrosine phosphorylation and DNA binding activity was inhibited by treatment with
      Jak specific inhibitor AG 490; however, it was not affected by the MEK1 inhibitor
      PD 98059. Moreover, treatment with AG 490 inhibited IL-6-induced proliferation of
      ACHN and 769P cells and induced apoptosis with the down-regulation of bcl-2 and
      the up-regulation of bax. CONCLUSIONS: This study identified STAT3, but not ERKs,
      to be a major mediator of IL-6-induced proliferation of renal cancer cells.
      Although ERKs were constitutively activated, ERKs were not found to be essential
      for the IL-6-induced proliferation and modulation of the STAT3 activity. Because
      the Jak specific inhibitor AG 490 effectively inhibited the IL-6-induced STAT3
      activity and induced apoptosis, the blockade of the STAT3 signaling pathways is
      considered to be potentially useful as a novel therapeutic approach for RCC.

PMID- 11849448
TI  - Pyridoxamine inhibits early renal disease and dyslipidemia in the streptozotocin
      diabetic rat.
AB  - BACKGROUND: Nonenzymatic reactions between sugars or lipids and protein and
      formation of advanced glycation and lipoxidation end products (AGE/ALEs)
      contribute to the chemical modification and cross-linking of tissue proteins with
      age. Accelerated formation of AGE/ALEs during hyperglycemia is implicated in the
      development of diabetic complications. In this study, we examined the effect of
      the AGE/ALE inhibitor pyridoxamine on chemical modification and cross-linking of
      collagen and development of renal disease in the streptozotocin-diabetic rat.
      METHODS: Diabetic rats were treated with pyridoxamine; parallel experiments were
      conducted with aminoguanidine, the prototype AGE inhibitor. Progression of renal
      disease was evaluated by measurements of albuminuria and plasma creatinine
      concentration. Plasma triglycerides, cholesterol, lactate and pyruvate were
      measured by enzymatic assays, and AGE/ALEs in skin collagen by HPLC and GC-MS
      assays. RESULTS: Pyridoxamine significantly inhibited the increase in
      albuminuria, plasma creatinine, hyperlipidemia and plasma lactate/pyruvate ratio
      in diabetic rats, without an effect on blood glucose or glycated hemoglobin.
      AGE/ALEs, fluorescence and cross-linking of skin collagen increased approximately
      twofold in diabetic versus control rats after seven months of diabetes.
      Pyridoxamine caused a significant (25 to 50%) decrease the AGE/ALEs,
      carboxymethyllysine and carboxyethyllysine, cross-linking and fluorescence in
      skin collagen of diabetic rats, but did not affect pentosidine. CONCLUSIONS:
      Pyridoxamine inhibits the progression of renal disease, and decreases
      hyperlipidemia and apparent redox imbalances in diabetic rats. Pyridoxamine and
      aminoguanidine had similar effects on parameters measured, supporting a mechanism
      of action involving AGE/ALE inhibition.

PMID- 11849449
TI  - Angiotensin II type 1 receptor blockade ameliorates tubulointerstitial injury
      induced by chronic potassium deficiency.
AB  - BACKGROUND: Chronic potassium (K+) deficiency, one of the well-known causes of
      renal tubulointerstitial injury, is associated with an alteration in vasoactive
      mediators including persistent generation of renal cortical angiotensin (Ang) II
      despite the suppression of plasma Ang II, and suppression of urinary
      nitrite/nitrate excretion. We tested the hypothesis that K+-deficiency-induced
      renal tubulointerstitial injury could be mediated by Ang II or a reduction in
      nitric oxide. METHODS: Rats were fed a K+-deficient diet (0.01% K+) alone, or
      with either losartan or l-arginine (L-Arg) in drinking water. Control rats were
      fed with a normal K+ diet (0.36% K+). At the end of 10 weeks, kidneys were
      excised and renal injury was evaluated. RESULTS: Serum K+ was similarly depressed
      in all three groups receiving the K+-deficient diet. Rats on the K+-deficient
      diet alone developed renal hypertrophy and tubulointerstitial fibrosis with an
      increase in tubular osteopontin expression, macrophage infiltration and type III
      collagen deposition. Administration of losartan significantly reduced renal
      hypertrophy and prevented tubulointerstitial injury in the cortex, although some
      medullary injury occurred. In contrast, administration of L-Arg did not attenuate
      tubulointerstitial injury in the cortex, despite a complete recovery of urinary
      nitrate excretion. Mild but significant improvement of tubular osteopontin
      expression and macrophage infiltration were observed in the medulla of L-Arg
      treated hypokalemic rats. CONCLUSIONS: These results indicate that hypokalemic
      renal injury is mediated, at least in part, by Ang II via the Ang II type 1
      receptor, with a lesser contribution mediated by a reduction in nitric oxide.
      Losartan may be beneficial in preventing hypokalemic tubulointerstitial injury.

PMID- 11849450
TI  - Meprin, a brush-border enzyme, plays an important role in hypoxic/ischemic acute
      renal tubular injury in rats.
AB  - BACKGROUND: It has been shown that non-congenic mice strains with lower levels of
      renal meprin develop less renal injury following renal ischemia and reperfusion.
      We have demonstrated that following ischemia-reperfusion renal injury, there is a
      rapid shift of meprin localization and intensity from the brush border to the
      cytoplasmic compartment, tubular lumens and the tubular basement membranes.
      Radical shifts in the localization of an activated enzyme to potentially
      sensitive areas of the tubule suggest a toxic role for meprin in ischemia
      reperfusion injury. Though meprin degrades extracellular matrix components and
      other substrates, to our knowledge meprin cytotoxicity has never been examined.
      Therefore, the first objective of this study was to determine if meprin is
      directly cytotoxic to renal cells in vitro. The second objective was to determine
      if inhibition of meprin is protective against hypoxia-reoxygenation injury in
      vitro and ischemia-reperfusion injury in vivo. METHODS: The immortalized porcine
      epithelial cell line (LLC-PK1) and Madin-Darby canine kidney (MDCK) cells in
      culture were exposed to meprin in various concentrations and for various times.
      Cell death was determined by Trypan Blue exclusion, lactate dehydrogenase (LDH)
      release and the 3-[4,5] dimethylthiazol-2,5-diphenyltetrazolium bromide (MTT)
      assay. Renal slices were used to examine the effect of the meprin inhibitor,
      actinonin, on hypoxic injury in vitro. Male Sprague-Dawley rats were used in
      ischemia-reperfusion injury studies to determine the effect of actinonin on renal
      function as measured by plasma urea nitrogen, creatinine and renal histology.
      RESULTS: Meprin is cytotoxic to LLC-PK1 and MDCK cells in a concentration and
      time dependent manner. The meprin inhibitor 1,10-phenanthroline completely
      abolished the cytotoxic effect. Renal slices exposed to hypoxia and hypoxia
      followed by reoxygenation showed marked cell death. Pre-treatment with the
      actinonin was markedly protective while not interfering with the hypoxia-induced
      fall in adenosine 5'-triphosphate (ATP) levels. In in vivo studies, rats exposed
      to ischemia/reperfusion injury were markedly protected against acute renal
      failure by IP treatment with actinonin. CONCLUSIONS: Meprin is cytotoxic to
      cultured renal tubular epithelial cells in vitro. Renal slices are protected from
      hypoxia-reoxygenation injury in vitro by the meprin inhibitor actinonin. Meprin
      inhibition is protective against rat renal hypoxia-reoxygenation injury. These
      data strongly support the concept that meprin is cytotoxic and may play a key
      role in renal ischemia-reperfusion induced renal injury.

PMID- 11849451
TI  - The gamma-Na+,K+-ATPase subunit assembles selectively with alpha1/beta1-Na+,K+
      ATPase but not with the colonic H+,K+-ATPase.
AB  - BACKGROUND: The ubiquitous Na+-pump (Na+,K+-ATPase) assembles as a heterodimer of
      composition alpha/beta in some nephron segments, while in other segments it may
      exist as a heterotrimer of composition alpha/beta/gamma. The gamma-subunit has
      been reported to increase the affinity of the Na+-pump for adenosine 5'
      triphosphate (ATP), and decrease affinity for both Na+ and K+. The alpha-subunit
      of the colonic H+,K+-ATPase (cHK) shares 75% sequence similarity with alpha1
      Na+,K+-ATPase (alpha1) and assembles with beta1-Na+,K+-ATPase (beta1) in distal
      colon and renal medulla. Differences in pharmacological properties have been
      ascribed to when heterologously expressed function has been compared to function
      in vitro. The purpose of this study was to determine if cHK might associate with
      the gamma-subunit of the Na+,K+-ATPase (gamma) as a possible explanation for
      these variations in function. METHODS: An antibody specific for the gamma was
      used in coimmunoprecipitation experiments to determine if the gamma assembles
      stably in vitro with cHK and beta1 in rat renal medulla or distal colon. RESULTS:
      Our results demonstrate that the gamma-subunit assembles specifically with the
      Na+-pump, but not with cHK. Furthermore, the gamma-subunit assembly was specific
      for rat kidney and was not observed in distal colon. CONCLUSION: Since the gamma
      subunit did not assemble with the cHK/beta1 complex, gamma-subunit assembly
      cannot explain those variations in ex vivo and in vitro pharmacologic properties
      ascribed to cHK.

PMID- 11849452
TI  - Calcium oxalate stone formation in genetic hypercalciuric stone-forming rats.
AB  - BACKGROUND: Over 54 generations, we have successfully bred a strain of rats that
      maximizes urinary calcium excretion. The rats now consistently excrete 8 to 10
      times as much calcium as controls, uniformly form poorly crystalline calcium
      phosphate kidney stones, and are termed genetic hypercalciuric stone-forming
      (GHS) rats. These rats were used to test the hypothesis that increasing urinary
      oxalate excretion would not only increase the supersaturation with respect to the
      calcium oxalate solid phase, but also would increase the ratio of calcium oxalate
      to-calcium phosphate supersaturation and result in calcium oxalate stone
      formation. METHODS: To increase urine oxalate excretion an oxalate precursor,
      hydroxyproline, was added to the diet of male GHS rats. The GHS rats were fed a
      standard 1.2% calcium diet alone or with 1%, 3% or 5% trans-4-hydroxy-l-proline
      (hydroxyproline). RESULTS: The addition of 1% hydroxyproline to the diet of GHS
      rats led to an increase in urinary oxalate excretion, which did not increase
      further with the provision of additional hydroxyproline. The addition of 1% and
      3% hydroxyproline did not alter calcium excretion while the provision of 5%
      hydroxyproline led to a decrease in urine calcium excretion. The addition of 1%
      hydroxyproline led to an increase in urinary calcium oxalate supersaturation,
      which did not further increase with additional hydroxyproline. The addition of 1%
      and 3% hydroxyproline did not alter urinary supersaturation with respect to
      calcium hydrogen phosphate while the addition of 5% hydroxyproline tended to
      lower this supersaturation. Compared to rats fed the control and the 3%
      hydroxyproline diet the addition of 5% hydroxyproline increased the ratio of
      calcium oxalate supersaturation to calcium phosphate supersaturation. Virtually
      all rats formed stones. In the control and 1% hydroxyproline group, all of the
      stones were composed of calcium and phosphate (apatite), in the 3% hydroxyproline
      group the stones were a mixture of apatite and calcium oxalate, while in the 5%
      hydroxyproline group all of the stones were calcium oxalate. CONCLUSIONS: The
      provision of additional dietary hydroxyproline to GHS rats increases urinary
      oxalate excretion, calcium oxalate supersaturation and the ratio of calcium
      oxalate-to-calcium phosphate supersaturation, resulting in the formation of
      calcium oxalate kidney stones. Thus, with the addition of a common amino acid,
      the GHS rats now not only model the most common metabolic abnormality found in
      patients with nephrolithiasis, hypercalciuria, but form the most common type of
      kidney stone, calcium oxalate.

PMID- 11849453
TI  - Studies on the pathophysiology of the low urine pH in patients with uric acid
      stones.
AB  - BACKGROUND: A very low urine pH is the major risk factor for uric acid stone
      formation. METHODS: A subgroup of patients with a history of uric acid stones and
      a persistently low urine pH (<5.5 for at least 12 h/day) were selected for
      detailed study. Based on their relative ammonium (NH(+)(4)) and sulfate (SO(2
      )(4)) excretions, patients were divided into two groups. RESULTS: The first group
      (N = 2) excreted 173 and 139% more NH(+)(4) than SO(2-)(4). Their daily urinary
      unmeasured anion excretion was higher than their calculated net diet alkali input
      (38 and 61 vs. 24 and 49 mEq, respectively). In the second group (N = 12),
      NH(+)(4) excretion was 69 +/- 5% that of SO(2-)(4). In 2 of 12, decreased renal
      ammoniagenesis was suspected due to a plasma potassium of 5.3 mmol/L and/or a
      lower GFR (65 and 59 L/day); these patients had an extremely low citrate
      excretion (3 and 1 mEq/day). In contrast, citrate excretion was not low in the
      remaining 10 patients (10.4 +/- 1.3 mEq/day). CONCLUSIONS: Patients in group 1
      needed a higher NH(+)(4) excretion possibly because of a H+ load from excessive
      renal excretion of organic anions. We speculate that an alkaline proximal tubular
      cell pH could be the basis for the low NH(+)(4) and high citrate excretions in 10
      of 12 patients in group 2. Dietary factors and/or a molecular lesion may
      contribute to their pathophysiology.

PMID- 11849454
TI  - Down-regulation of urea transporters in the renal inner medulla of lithium-fed
      rats.
AB  - BACKGROUND: Lithium is commonly used to treat bipolar psychiatric disorders but
      can cause reduced urine concentrating ability. METHODS: To test whether lithium
      alters UT-A1 or UT-B urea transporter protein abundance or UT-A1 phosphorylation,
      rats were fed a standard diet supplemented with LiCl for 10 or 25 days, and then
      compared to pair-fed control rats. To investigate another potential mechanism for
      decreased urea transport, inner medullary collecting duct (IMCD) suspensions from
      lithium-fed or control rats were incubated with 32P-orthophosphate to measure the
      phosphorylation of UT-A1. RESULTS: In lithium-fed rats (25 days), UT-A1 abundance
      was reduced to 50% of control rats in IM tip and to 25% in IM base, and UT-B
      abundance was reduced to 40% in IM base. Aquaporin-2 (AQP2) protein abundance was
      reduced in both IM regions. Vasopressin (100 pmol/L) increased UT-A1
      phosphorylation in IMCD suspensions from control but not from lithium-fed rats; a
      higher vasopressin concentration (100 nmol/L) increased UT-A1 phosphorylation in
      control and lithium-fed rats. CONCLUSIONS: Decreases in UT-A1, UT-B, and AQP2
      protein abundance, and/or vasopressin-stimulated phosphorylation of UT-A1, can
      contribute to the reduced urine concentrating ability that occurs in lithium
      treated rats.

PMID- 11849455
TI  - Cl- channels in basolateral TAL membranes. XVI. MTAL and CTAL cells each contain
      the mRNAs encoding mmClC-Ka and mcClC-Ka.
AB  - BACKGROUND: Our prior data indicate that two separate but homologous basolateral
      chloride (Cl-) channels, mmClC-Ka and mcClC-Ka, are the principal mediators of
      net Cl- absorption in mouse medullary thick ascending limb (MTAL) and cortical
      thick ascending limb (CTAL) cells, respectively. In the present studies, we
      evaluated the possibility that there might be translational or post-translational
      suppression of mmClC-Ka and mcClC-Ka activity in CTAL and MTAL cells,
      respectively. METHODS: Polymerase chain reaction (PCR) fragments were prepared
      that were highly specific for either mmClC-Ka or mcClC-Ka, the cDNAs encoding
      mmClC-Ka and mcClC-Ka, respectively. RESULTS: Using reverse transcription (RT)
      PCR with these highly specific products, mRNAs specific for non-homologous
      channel sequences in either mmClC-Ka or mcClC-Ka were present in both MTAL and
      CTAL cells. CONCLUSIONS: Both mouse MTAL and CTAL cells contain the mRNAs
      encoding mmClC-Ka and mcClC-Ka. There may be translational or post-translational
      suppression of mmClC-Ka activity in CTAL cells, and of mcClC-Ka activity in MTAL
      cells.

PMID- 11849456
TI  - Increased expression of TGF-beta1 and IGF-I in inflammatory stenotic lesions of
      hemodialysis fistulas.
AB  - BACKGROUND: Hemodialysis fistula dysfunction due to stenotic lesions remains a
      frequent cause of hospitalization for hemodialysis patients. Transforming growth
      factor-beta(TGF-beta) and insulin-like growth factor-I (IGF-I) are known to be
      involved in atherogenesis. The latent TGF-beta1 binding protein-1 (LTBP-1)
      targets extracellular matrix (ECM) interactions and is involved in the regulation
      of TGF-beta latency. METHODS: We investigated the expression of TGF-beta1, LTBP-1
      and IGF-I in 15 occluded or severely narrowed vein segments of primary
      arteriovenous fistulas, in 29 non-stenosed control veins from uremic, pre
      dialysis patients, and in 15 non-stenosed control saphenous veins obtained from
      patients undergoing aortocoronary bypass grafting. Immunohistochemistry was
      performed on snap-frozen tissue specimens using antibodies recognizing either the
      latency-associated peptide of TGF-beta1 (96-1), LTBP-1 (Ab39) or IGF-I. Serum
      levels of TGF-beta1 and IGF-I were determined by commercially available IRMA.
      RESULTS: In stenosed hemodialysis fistulas, a pronounced intimal thickening with
      deposition of ECM was observed with light and electron microscopy. Infiltrating
      cells were seen in stenosed vessels, mostly in areas of intimal hyperplasia and
      in the media. TGF-beta1, LTBP-1 and IGF-I expression were mostly localized in the
      neointimal and medial layers, and were significantly higher than in the control
      groups. A positive correlation between the presence of inflammatory cells and the
      staining intensity for TGF-beta1, LTBP-1 and IGF-I was found in all vessels
      analyzed. CONCLUSION: Neointimal thickening of primary arteriovenous fistulas
      represents a local inflammatory process and appears to be associated with
      increased protein expression of TGF-beta1 and IGF-I. While local IGF-I is likely
      to stimulate smooth muscle cell proliferation in this setting, TGF-beta1 may be
      an important trigger of ECM production and deposition.

PMID- 11849458
TI  - Association of the tissue kallikrein gene promoter with ESRD and hypertension.
AB  - BACKGROUND: Kallikreins have long been implicated in human essential hypertension
      and associated complications. In particular, low urinary kallikrein excretion has
      been associated with hypertension and renal disease in African Americans. In an
      effort to identify the source of differential kallikrein excretion, we
      investigated the promoter of KLK1, the tissue kallikrein gene. The KLK1 promoter
      is uniquely polymorphic with a poly-G length polymorphism coupled with multiple
      single base substitutions. In this report, we genetically evaluated the
      association of KLK1 gene promoter alleles with end-stage renal disease (ESRD) in
      African Americans. METHODS: A total of 15 haplotypes were identified in the KLK1
      promoter region through detailed DNA sequence analysis. This polymorphic region
      was then genetically evaluated for association with ESRD in African Americans
      with diabetic and non-diabetic etiologies of ESRD. RESULTS: The complex
      polymorphic nature of the promoter presents challenges to determining the
      alleles. We have redefined the region as six separate loci: five substitution
      loci and one length locus. The length locus was defined as G repeats starting at
      position -130 and ending at -121 on the gene. Among four relevant substitution
      loci for this study, one at position -131, just outside the G repeats, is an A-to
      G substitution. The other three variant positions are -129, -128, and -127, all G
      to-C substitutions within the G repeats. This region was genotyped in African
      American subjects with and without ESRD using semiautomated sequencing. Four
      different G repeat alleles ranging from 11.8% for 12 Gs to 52.3% for 10 Gs were
      observed in 86 control subjects. The C substitution of Gs ranges from 2.9% at
      position -127 to 8.2% at -129. When affected probands from each of 76
      hypertensive ESRD families were genotyped, an association for the 12 G allele,
      the longest of the length locus alleles, was detected (allele specific P = 0.004
      and locus total P = 0.02). When all ESRD affected individuals with hypertension
      from each family (107 patients in total) were used in the analysis, an even
      stronger association was observed for this allele (allele specific P = 0.003,
      locus total P = 0.01). This allele was more frequent in the hypertensive (non
      diabetic) patients (0.20 in probands and 0.19 in all ESRD cases) than in the
      controls (0.12). No evidence of association in diabetic ESRD patients was
      observed (P = 0.93). CONCLUSIONS: The KLK1 promoter is uniquely polymorphic. The
      observed genetic association suggests an etiologic effect of the KLK1 promoter on
      hypertension and/or hypertension associated ESRD.

PMID- 11849457
TI  - Angiotensin II infusion ameliorates the early phase of a mesangioproliferative
      glomerulonephritis.
AB  - BACKGROUND: Inhibition of the renin-angiotensin system slows the progression of
      chronic renal disease. METHODS: To test whether angiotensin II (Ang II) infusion
      aggravates or ameliorates an acute glomerulonephritis, the peptide was infused
      (200 ng/min by osmotic minipump) in rats with an anti-thymocyte antibody-induced
      glomerulonephritis (ATS). RESULTS: Ang II significantly increased blood pressure.
      Following injection of the antibody, similar glomerular binding of rabbit IgG and
      rat complement C3 was detected in ATS and Ang II+ATS rats, indicating no
      differences in delivery and binding of the antibody. Ang II infusion, however,
      induced a significant reduction in glomerular monocyte infiltration, cell
      proliferation and matrix expansion in nephritic rats compared to rats with
      nephritis without Ang II. The antiproliferative effect of Ang II was inhibited by
      the Ang II type 1 (AT1) receptor blocker irbesartan, but not by the AT2 receptor
      blocker PD 123319, indicating that this effect was likely transduced by AT1
      receptors. Norepinephrine infusion (600 ng/min) produced a similar degree of
      hypertension, but did not affect glomerular proliferation in nephritic rats. Ang
      II induced the glomerular expression of the cell cycle inhibitor p27KIP1 and of
      transforming growth factor-beta (TGF-beta) and inhibited expression of monocyte
      chemotactic protein 1 (MCP-1). CONCLUSION: Ang II surprisingly ameliorates
      glomerular monocyte infiltration, proliferation and matrix expansion in ATS
      nephritis. Ang II-mediated induction of cyclin kinase inhibitors and TGF-beta may
      contribute to the protection of the glomerulus from inflammatory injury by
      inducing cell cycle arrest and attenuating activation of local and recruited
      cells. Alternatively, Ang II might protect the kidney at least in part by less
      inflow of disease activators due to reduction of renal blood flow. Therefore,
      activation of the renin-angiotensin system may have protective effects in certain
      pathophysiological situations.

PMID- 11849459
TI  - Betaine supplementation decreases post-methionine hyperhomocysteinemia in chronic
      renal failure.
AB  - BACKGROUND: Fasting and post-methionine load hyperhomocysteinemia are independent
      risk factors for vascular disease that are common in chronic renal failure.
      Folate decreases but seldom normalizes fasting total homocysteine (tHcy)
      concentrations in such patients. Glycine betaine (GB) is known to decrease tHcy
      in other clinical settings, but whether it is beneficial in chronic renal failure
      has not been established. METHODS: We conducted a crossover-controlled trial in
      36 patients with chronic renal failure to determine if oral GB decreased fasting
      or post-methionine tHcy concentrations. All subjects received, in randomized
      sequence, 5-mg folic acid and 50-mg pyridoxine daily, with or without GB 4-g
      daily, for three months each. Fasting plasma tHcy, GB, folate, B vitamins, serum
      lipids and creatinine were measured at one and three months, and methionine load
      tests were performed at the end of each three-month treatment phase. RESULTS: GB
      and N,N-dimethylglycine (DMG) levels in plasma and urine increased markedly
      during GB treatment. Fasting tHcy decreased from baseline with both treatments
      but did not differ between treatments. Post-methionine tHcy decreased with both
      treatments and was 18% lower on GB than on folate and pyridoxine alone (P <
      0.001). There were small increases in lipids during treatment with GB but the
      ratio of total: HDL cholesterol was unchanged. CONCLUSIONS: GB supplementation
      had no effect on fasting tHcy in patients with chronic renal failure who were
      folate and pyridoxine replete, but it significantly decreased tHcy concentrations
      after methionine loading.

PMID- 11849460
TI  - Predictors of antihypertensive response to a standard dose of hydrochlorothiazide
      for essential hypertension.
AB  - BACKGROUND: Determinants of inter-individual variation in blood pressure (BP)
      response to antihypertensive therapy remain largely unknown. Although differences
      in race, age and measures of the renin-angiotensin-aldosterone system (RAAS) have
      been associated with variation in blood pressure response to hydrochlorothiazide,
      whether these characteristics make additive contributions to predicting response
      has not been established. We conducted a comprehensive search for predictors of
      BP response to a standard dose of hydrochlorothiazide in a biracial sample to
      estimate how much inter-individual variation in BP response could be explained by
      all of the identified predictors. METHODS: After withdrawal of antihypertensive
      medications for at least four weeks (baseline) and stabilization on a diet
      approximating 150 mmol sodium per day, 225 African American and 280 Caucasian
      subjects with diagnosed essential hypertension were treated for four weeks with
      hydrochlorothiazide 25 mg per day. At baseline and the end of treatment, subjects
      were admitted to the General Clinical Research Center for measurement of activity
      of the RAAS and other regulators of BP. Characteristics measured at study
      enrollment, at baseline, and in response to drug treatment were incorporated
      stepwise into linear regression models in order to quantify their additive
      contributions to predicting BP responses to hydrochlorothiazide. RESULTS: Black
      race and female gender were both associated with significantly greater systolic
      (SBP) and diastolic (DBP) blood pressure responses to hydrochlorothiazide.
      Together the combined effects of race and gender accounted for 11% inter
      individual variation in SBP response (P < 0.0001) and 4% of inter-individual
      variation in DBP response (P < 0.0001). Additional statistically significant
      predictors of greater systolic and diastolic responses to hydrochlorothiazide
      included, shorter duration of diagnosed or treated hypertension (P < 0.001),
      higher baseline BP level (P < 0.0001), lower baseline plasma renin activity (P <
      0.05), lower baseline urinary aldosterone excretion (P < 0.002), and greater
      decrease in urinary sodium excretion (P < or = 0.004). Greater decrease in weight
      was an additional statistically significant predictor of SBP but not DBP
      response, and older age was a predictor of diastolic but not SBP response. The
      combined effects of all identified predictors accounted for 38% of inter
      individual variation in SBP response (P < 0.0001) and 20% of inter-individual
      variation in DBP response (P < 0.0001). CONCLUSIONS: A systematic search reveals
      numerous predictors of BP response to a standard antihypertensive dose of
      hydrochlorothiazide. However, because the majority of inter-individual variation
      in SBP and DBP responses remains unexplained, there is considerable opportunity
      for future investigations to improve the ability to predict individual BP
      responses to antihypertensive drug therapy.

PMID- 11849461
TI  - Enhanced renal cortical vascularization in experimental hypercholesterolemia.
AB  - BACKGROUND: Experimental hypercholesterolemia is associated with pro-inflammatory
      changes and impaired regulation of tissue perfusion, which may lead to
      neovascularization. However, it is yet unknown whether such changes take place in
      the kidney. In this study, using a novel three-dimensional (3-D) micro computed
      tomography technique we tested the hypothesis that hypercholesterolemia was
      associated with increased microvascular density in the renal cortex. METHODS:
      Kidneys were excised from pigs after 12 weeks of either a normal (N = 6) or high
      cholesterol (HC; N = 5) diet, histology slides processed, and a segmental renal
      artery injected with a radio-opaque intravascular silicone polymer. Renal samples
      were scanned with micro computed-tomography, transverse and three-dimensional
      images were reconstructed, and microvessels (80 to 360 microm in diameter)
      counted in situ. RESULTS: Serum cholesterol levels were significantly higher in
      hypercholesterolemic compared to normal pigs (383 +/- 76 vs. 81 +/- 7 mg/dL, P <
      0.01), and microvascular spatial density was significantly higher in their inner
      and middle renal cortex (189 +/- 7 vs. 126 +/- 6 microvessels/cm2, P < 0.0001).
      Hypercholesterolemic kidneys also showed mild interstitial mononuclear
      infiltration and heavier immunostaining of vascular endothelial growth factor,
      but no other signs of morphological damage. CONCLUSIONS: These results
      demonstrate that early diet-induced hypercholesterolemia is associated with
      increased microvascular density in the renal cortex, which precedes signs of
      overt renal morphological damage. These alterations may potentially affect
      regulation and/or spatial distribution of intrarenal blood flow in
      hypercholesterolemia, and may participate in renal disease progression.

PMID- 11849462
TI  - Propionyl-L-carnitine prevents renal function deterioration due to
      ischemia/reperfusion.
AB  - BACKGROUND: Ischemia-reperfusion injury after organ transplantation is a major
      cause of delayed graft function. Prevention of post-transplant ischemia acute
      renal failure is still elusive. METHODS: The present study was designed to
      examine whether propionyl-l-carnitine, an acyl derivative of carnitine involved
      in fatty acid oxidation pathway and adenosine 5'-triphosphate (ATP) generation of
      mitochondria, prevented renal function deterioration and structural injury
      induced by ischemia-reperfusion in an ex vivo rat model of isolated perfused
      kidney (IPK) preparation and in vivo in a model of syngeneic kidney
      transplantation. RESULTS: In the model of ischemia (20 or 40 min)/reperfusion (90
      or 70 min) in IPK, untreated kidneys showed a marked reduction of glomerular
      filtration rate (GFR) and renal perfusate flow (RPF) as compared to baseline,
      when perfusion was established by restoring effective perfusion pressure to 100
      mm Hg. Exposure of kidneys to propionyl-l-carnitine before establishing the
      ischemia insult to tissue, largely prevented renal function impairment. Pre
      exposure of ischemic kidneys to propionyl-l-carnitine largely reduced the percent
      of lactate dehydrogenase (LDH), a cell injury marker, released into the perfusate
      after reperfusion as compared to untreated ischemic kidneys. Histologic findings
      showed very mild post-ischemic lesions in kidneys exposed to propionyl-l
      carnitine as compared to untreated ischemic kidneys. Immunohistochemical
      detection of 4-hydroxynonenal protein adduct, a major product of lipid
      peroxidation, was very low in kidney infused with propionyl-l-carnitine and
      exposed to ischemia/reperfusion as compared to untreated ischemic kidneys. ATP
      levels were not affected by propionyl-l-carnitine treatment. Renal function of
      kidneys exposed for four hours to cold Belzer UW solution added with propionyl-l
      carnitine and transplanted to binephrectomized recipients was largely preserved
      as compared to untreated ischemic grafts. Propionyl-l-carnitine almost completely
      prevented polymorphonuclear cell graft infiltration and reduced tubular injury at
      16 hours post-transplant. CONCLUSIONS: These data indicate that propionyl-l
      carnitine is of value in preventing decline of renal function that occurs during
      ischemia-reperfusion. The beneficial effect of propionyl-l-carnitine possibly
      relates to lowering lipid peroxidation and free radical generation that
      eventually results in the preservation of tubular cell structure. The efficacy of
      propionyl-l-carnitine to modulate ischemia-reperfusion injury in these models
      opens new perspectives for preventing post-transplant delayed graft function.

PMID- 11849463
TI  - Polymorphism of the cytokine genes and IgA nephropathy.
AB  - BACKGROUND: IgA nephropathy (IgAN) is a form of chronic glomerulonephritis of
      unknown etiology and pathogenesis. Cytokine gene polymorphisms regulate cytokine
      production and play a role in immune and inflammatory responses; these
      immunological responses thus are possibly involved in the etiology and
      pathogenesis of IgAN. METHODS: We studied by polymerase chain reaction (PCR)
      polymorphisms of important cytokine genes of inflammation interleukin-1 (IL
      1beta), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and
      interleukin-1 receptor antagonist (IL-1Ra) in 167 patients with IgAN and 400
      healthy blood donor controls. IgAN patients had been followed up for 6 to 17
      (median 11) years from renal biopsy. RESULTS: Carriage of the IL-1beta allele 2
      (IL1beta2) or IL-1Ra allele 2 (IL1RN*2) was associated with an increased risk of
      IgAN. These alleles were highly linked and the odds ratio (OR) of IgAN for
      carriage of both alleles was 1.8 (95% confidence interval 1.2 to 2.6; P = 0.002).
      Carriage of the TNF-alpha allele 2 (TNF2) was associated with a decreased risk of
      IgAN (OR 0.5, range 0.3 to 0.7; P = 0.001). The risk of IgAN was found to be
      highest in those carrying IL1beta2 and IL1RN*2 but not TNF2 as compared to those
      who did not carry both of these IL-1 cluster genes and were carriers of TNF2 (OR
      5.0 (2.4-10.3); P < 0.001). None of the polymorphisms studied was associated with
      poor prognosis. CONCLUSION: Carriage of IL1beta2 and IL1RN*2 together with non
      carriage of TNF2 is associated with increased susceptibility, but not with a
      prognosis of IgAN.

PMID- 11849464
TI  - Effects of aggressive blood pressure control in normotensive type 2 diabetic
      patients on albuminuria, retinopathy and strokes.
AB  - BACKGROUND: Although several important studies have been performed in
      hypertensive type 2 diabetic patients, it is not known whether lowering blood
      pressure in normotensive (BP <140/90 mm Hg) patients offers any beneficial
      results on vascular complications. The current study evaluated the effect of
      intensive versus moderate diastolic blood pressure (DBP) control on diabetic
      vascular complications in 480 normotensive type 2 diabetic patients. METHODS: The
      current study was a prospective, randomized controlled trial in normotensive type
      2 diabetic subjects. The subjects were randomized to intensive (10 mm Hg below
      the baseline DBP) versus moderate (80 to 89 mm Hg) DBP control. Patients in the
      moderate therapy group were given placebo, while the patients randomized to
      intensive therapy received either nisoldipine or enalapril in a blinded manner as
      the initial antihypertensive medication. The primary end point evaluated was the
      change in creatinine clearance with the secondary endpoints consisting of change
      in urinary albumin excretion, progression of retinopathy and neuropathy and the
      incidence of cardiovascular disease. RESULTS: The mean follow-up was 5.3 years.
      Mean BP in the intensive group was 128 +/- 0.8/75 +/- 0.3 mm Hg versus 137 +/-
      0.7/81 +/- 0.3 mm Hg in the moderate group, P < 0.0001. Although no difference
      was demonstrated in creatinine clearance (P = 0.43), a lower percentage of
      patients in the intensive group progressed from normoalbuminuria to
      microalbuminuria (P = 0.012) and microalbuminuria to overt albuminuria (P =
      0.028). The intensive BP control group also demonstrated less progression of
      diabetic retinopathy (P = 0.019) and a lower incidence of strokes (P = 0.03). The
      results were the same whether enalapril or nisoldipine was used as the initial
      antihypertensive agent. CONCLUSION: Over a five-year follow-up period, intensive
      (approximately 128/75 mm Hg) BP control in normotensive type 2 diabetic patients:
      (1) slowed the progression to incipient and overt diabetic nephropathy; (2)
      decreased the progression of diabetic retinopathy; and (3) diminished the
      incidence of stroke.

PMID- 11849465
TI  - Mycophenolate mofetil treatment for primary glomerular diseases.
AB  - BACKGROUND: Treatment of primary glomerular diseases may be unsuccessful or have
      potential toxicities. Therefore, we evaluated the use of mycophenolate mofetil
      (MMF) for empirical treatment of primary glomerulopathies. METHODS: Forty-six
      patients with biopsy-proven primary glomerulopathies received MMF for > or =3
      months as adjunctive or primary treatment. Median (range) 24-hour urine protein
      to creatinine ratio (Up/c) and serum creatinine at the start and end of MMF
      therapy were compared using the Wilcoxon signed-ranks test. RESULTS: Overall, the
      median Up/c decreased from 4.7 (range <0.1, 20.3) to 1.1 (<0.1, 14.3; P < 0.001)
      at the end of MMF treatment with no significant change in median serum creatinine
      1.3 (0.6 to 6.1) to 1.2 (0.5 to 6.5) mg/dL. Median serum albumin increased from
      3.4 (1.4, 4.6) to 4.1 (1.7, 48) g/dL (P < 0.001) and the median serum cholesterol
      decreased from 270 (148, 795) to 220 (140, 309) mg/dL (P < 0.001) post-treatment.
      For those with minimal change disease, a complete steroid withdrawal was
      accomplished in 5/6 steroid dependent patients. Focal segmental
      glomerulosclerosis (FSGS) patients had a median Up/c that decreased from 2.7
      (0.1, 20.3) to 0.8 (<0.1, 8.2; P = 0.001) in 18 patients. In membranous
      nephropathy (MN) patients, the median Up/c decreased from 7.3 (0.1, 18.5) to 1.5
      (<0.1, 14.3) (P = 0.001) in 17 patients. No significant change in median serum
      creatinine was detected in FSGS or MN patient groups during treatment.
      CONCLUSIONS: Empirical MMF therapy in the majority of patients with primary
      glomerulopathies was well tolerated and achieved the goals of steroid withdrawal,
      improvement of nephrotic syndrome, and stabilization of renal function.

PMID- 11849466
TI  - Race-specific association of lipoprotein(a) with vascular access interventions in
      hemodialysis patients: the CHOICE Study.
AB  - BACKGROUND: Elevated serum levels of lipoprotein(a) [Lp(a)] and low molecular
      weight apolipoprotein(a) [apo(a)] isoforms are associated with atherothrombotic
      disease in the general population and in patients with kidney failure. Lp(a) may
      be more atherothrombotic in whites than in blacks. Data on the relation of Lp(a)
      and apo(a) isoform size to hemodialysis vascular access complications are
      limited. METHODS: We analyzed the intervention-free survival of the first
      arteriovenous (AV) access among 215 white and 112 black incident hemodialysis
      patients participating in the CHOICE Study, a national multicenter prospective
      cohort study. RESULTS: Median levels of Lp(a) protein were higher among blacks
      than whites (81.0 versus 37.5 nmol/L; P < 0.001) and inversely correlated with
      apo(a) isoform size (r = -0.57; P < 0.001). The incidence rate of access
      interventions was much higher in synthetic grafts (N = 193) than native fistulae
      (N = 134; 1.0 vs. 0.5 interventions per access-year; P < 0.001) and in patients
      with kidney failure primarily due to diabetes mellitus (N = 161) than others (N =
      166; 0.9 vs. 0.6; P < 0.01), but did not differ by race. Blacks in the highest
      race-specific Lp(a) quartile (>145 nmol/L) had a significantly higher incidence
      rate than other blacks (1.4 vs. 0.7; P = 0.04), whereas no association was found
      in whites. The association in blacks remained after adjustment for access type
      and other characteristics (relative hazard = 1.68; 95% confidence interval: 0.98
      to 2.86). No association was found with apo(a) isoform size in either race.
      CONCLUSIONS: Elevated Lp(a) may be a risk factor for arteriovenous access
      complications among black hemodialysis patients. Future studies should explore
      this possibility and be adequately powered to allow race-specific analyses.

PMID- 11849467
TI  - In vivo detection of acute rat renal allograft rejection by MRI with USPIO
      particles.
AB  - BACKGROUND: Magnetic resonance imaging (MRI) for non-invasively detecting renal
      rejection was developed by monitoring the accumulation of macrophages labeled
      with dextran-coated ultrasmall superparamagnetic iron oxide (USPIO) particles at
      the rat renal allografts during acute rejection. METHODS: Five groups of male
      rats with DA-->BN renal allografts and one group with BN-->BN renal isografts
      were investigated by MRI before, immediately after, and 24 hr after intravenous
      infusion with different doses of USPIO particles. All infusions were done on post
      operative day 4. MRI experiments were carried out in a 4.7-Tesla instrument using
      a gradient echo sequence. RESULTS: MR signal intensity (MRSI) of the cortex was
      found to decrease with higher dosages of USPIO particles. In the absence of USPIO
      infusion, a decrease in MRSI was seen in the medulla region, presumably due to
      hemorrhage associated with renal graft rejection, while no significant change was
      observed in the cortex. The optimal dose of USPIO particles for visualizing
      rejection-associated changes in our rat kidney model appears to be 6 mg Fe/kg
      body weight. Iron staining results correlated with the MRSI data, indicating that
      the signal reduction in the MR images was due to the presence of iron.
      Immunohistochemical results indicated that USPIO particles were mostly taken up
      by infiltrating macrophages in the rejecting grafts. CONCLUSIONS: Our results
      suggest that MRI with intravenous administration of dextran-coated USPIO
      particles appears to be a valuable and promising tool that can be used as a non
      invasive and sensitive method to detect graft rejection in renal transplantation.

PMID- 11849468
TI  - Management of hemodialysis catheter-related bacteremia with an adjunctive
      antibiotic lock solution.
AB  - BACKGROUND: Tunneled dialysis catheters are complicated by frequent systemic
      infections. Standard therapy of catheter-associated bacteremia involves both
      systemic antibiotics and catheter replacement. Recent data suggest that biofilms
      in the catheter lumen are responsible for the bacteremia, and that instillation
      of an antibiotic lock (highly concentrated antibiotic solution) into the catheter
      lumen after dialysis sessions can eradicate the biofilm. METHODS: We analyzed
      prospectively the efficacy of an antibiotic lock protocol, in conjunction with
      systemic antibiotics, for treatment of patients with dialysis catheter-associated
      bacteremia without catheter removal. Protocol success was defined as resolution
      of fever and negative surveillance cultures one week following completion of the
      protocol. Protocol failure was defined as persistence of fever or surveillance
      cultures positive for any pathogen. In addition, infection-free catheter survival
      was compared to that observed in institutional historical control patients
      treated with catheter replacement. RESULTS: Blood cultures were positive in 98 of
      129 of episodes (76%) in which patients dialyzing with a catheter had fever or
      chills. Protocol success occurred in 40 of 79 infected patients (51%) treated
      with the antibiotic lock. Protocol failure occurred in 39 cases (49%): 7 had
      persistent fever, 15 had positive surveillance cultures (9 for Candida and 6 for
      bacteria), and 17 required catheter removal due to malfunction. Each of the
      pathogens in the surveillance cultures was different from the original pathogen
      in that patient. Eight of the 9 secondary Candida infections and all 6 secondary
      bacterial infections resolved after catheter exchange and specific antimicrobial
      treatment. Overall catheter survival with the antibiotic lock protocol was
      similar to that observed among patients managed with catheter replacement (median
      survival, 64 vs. 54 days, P = 0.24). CONCLUSIONS: Use of an antibiotic lock, in
      conjunction with systemic antibiotic therapy, can eradicate catheter-associated
      bacteremia while salvaging the catheter in about one half of cases. Moreover,
      this management approach offers clinical advantages over routine catheter
      exchange.

PMID- 11849469
TI  - Association between interleukin-6 and carotid atherosclerosis in hemodialysis
      patients.
AB  - BACKGROUND: Interleukin-6 (IL-6) is associated with cardiovascular complications
      in general subjects. Although blood IL-6 is greatly elevated in hemodialysis (HD)
      patients, the role of IL-6 in the advance of atherosclerosis remains to be
      determined. METHODS: We conducted a cross-sectional study to investigate the
      relationship between circulating IL-6 and carotid atherosclerotic changes in 156
      HD patients (age 58 +/- 1 years; time on HD treatment 13 +/- 1 years; 97 males
      and 59 females). Serum IL-6, IgG and IgA titers of Chlamydia pneumoniae
      antibodies, the intima-media thickness (IMT) and the cross-sectional intima-media
      area (IMarea) of the carotid arteries were measured by ultrasonography in each
      patient. RESULTS: Serum IL-6 levels were significantly higher in HD patients
      (2.04 +/- 0.16 pg/mL) compared to normal age-matched control subjects (0.31 +/-
      0.06 pg/mL, N = 24). Circulating log IL-6 levels were positively correlated with
      IMT (r = 0.278, P < 0.01) and IMarea (r = 0.344, P < 0.01), respectively. A
      stepwise multiple regression analysis revealed that IL-6 became significant
      predictors for IMT and IMarea but not for aortic wall calcification at L2/3
      vertebrae. Serum log IL-6 was significantly correlated with IgG (r = 0.277, P <
      0.01) and IgA titers of anti-Chlamydia antibodies (r = 0.192, P < 0.02). Serum
      IgA anti-Chlamydia titers were also correlated with the maximal diameter of
      carotid plaque (r = 0.293, P < 0.04). CONCLUSIONS: These findings suggested that
      IL-6 is associated with the severity of carotid atherosclerosis in HD patients.
      Persistent chronic chlamydial infection may be related, in part, to the advance
      of carotid plaque enlargement in dialysis patients.

PMID- 11849470
TI  - Middle molecule and small protein removal in children on peritoneal dialysis.
AB  - BACKGROUND: Dialysis efficiency has a great influence on the outcome of patients.
      Few data are available on the removal of solutes with molecular weights higher
      than urea and creatinine. The aim of our study was to assess the transport and
      the removal of substances with molecular weights up to 15 kD and to evaluate the
      contribution of residual renal function in peritoneal dialysis (PD) children.
      METHODS: Seventeen patients of 12 +/- 4 years undergoing automated PD were
      studied. Ten patients had 563 +/- 355 mL/day of urine output, and 7 were anuric.
      During a standardized nightly intermittent PD (NIPD) session, a single-injection
      inulin clearance was performed. Urea, creatinine, inulin (measured by HPLC),
      cystatin C and beta2-microglobulin (beta2m) were measured in blood, urine and
      dialysate. Clearances (L/week/1.73 m2) and weekly solute removal index (SRI) were
      calculated for all the solutes; weekly Kt/V was calculated for urea. RESULTS: In
      non-anuric versus anuric patients the total clearances were: urea 82.6 +/- 18.3
      versus 71.3 +/- 26.4; creatinine 82.7 +/- 28.6 versus 47.8 +/- 18.8; inulin 42.8
      +/- 11.3 versus 32.8 +/- 20.4; beta2m 14.2 +/- 13.8 versus 9.2 +/- 8.3; cystatin
      C 20.2 +/- 9.4 versus 9.7 +/- 4.8. In the patients with residual diuresis, the
      urea was removed mainly by PD (69.2%), while inulin, beta2m and cystatin C were
      removed by renal clearance (64.0%, 79.5% and 62.8%, respectively). Total,
      peritoneal and renal weekly Kt/V values in the subjects with residual renal
      function, were 2.86 +/- 0.70, 1.99 +/- 0.40 and 0.87 +/- 0.43, respectively.
      Peritoneal weekly Kt/V in the anuric patients was 2.36 +/- 0.85; total weekly
      Kt/V in the total group was 2.65 +/- 0.78. Weekly SRIs in non-anuric versus
      anuric patients were: urea 2.56 +/- 0.58 versus 2.09 +/- 0.74; creatinine 2.66 +/
      0.73 versus 1.46 +/- 0.56; inulin 2.36 +/- 0.92 versus 1.64 +/- 1.60; beta2m
      1.26 +/- 1.10 versus 1.20 +/- 1.90; cystatin C 1.72 +/- 0.83 versus 1.58 +/-
      1.62. CONCLUSIONS: Solutes removed during PD tend to decrease following an
      increase in molecular weight of the substance. Since anuric patients are at
      higher risk of middle molecule and small protein accumulation, more attention
      should be paid to the removal of middle molecules. Further studies should be
      undertaken to evaluate whether removing them has a clinical impact and to
      determine their threshold levels.

PMID- 11849471
TI  - Lecithinized superoxide dismutase reduces cold ischemia-induced chronic allograft
      dysfunction.
AB  - BACKGROUND: Chronic renal allograft failure (CAF) is influenced by both allo
      dependent and independent factors and is a major cause of graft loss in clinical
      renal transplantation. We evaluated a novel membrane-bound free radical
      scavenger, lecithinized superoxide dismutase (lec-SOD), to determine its
      potential in limiting the harmful effects of ischemia/reperfusion injury on CAF.
      METHODS: Fisher rat kidneys were stored for either 1 hour or 18 hours in cold
      Marshall's preservation solution either with or without lec-SOD and transplanted
      into Lewis recipients. RESULTS: Within 3 days of transplantation, an early
      inflammatory response involving granulocytes and macrophages was detected in
      renal allografts exposed to 18 hours cold ischemia that was significantly reduced
      by preservation with lec-SOD. By 24 weeks post-transplantation, elevated
      proteinuria and detection of apoptotic cells was observed in kidneys exposed to
      18 hours of cold ischemia, that was attenuated by preservation with lec-SOD (P <
      0.05). However, up-regulated expression of intracellular adhesion molecule-1
      (ICAM-1) and major histocompatibility complex (MHC) Class II together with a T
      lymphocyte infiltration were observed at 24 weeks that was not prevented by
      preservation with lec-SOD. CONCLUSIONS: These results demonstrate that
      ischemia/reperfusion injury, apoptotic cell death and allo-immune responses may
      be exacerbated by cold ischemia and accelerate the development of CAF.
      Preservation with lec-SOD may protect against the early damage induced by cold
      ischemia and reperfusion injury.

PMID- 11849472
TI  - Superficialization of the wrist native arteriovenous fistula for effective
      hemodialysis vascular access construction.
AB  - BACKGROUND: It is commonly known that the best type of vascular access for
      chronic hemodialysis, defined as the one with the lowest number of complications
      and longest use, is the primary (Brescia-Cimino) radiocephalic fistula. One
      reason for the impossibility of its creation is that the vein vessel on the
      forearm is located too deeply, which is primarily caused by the patients'
      obesity. METHODS: In 24 obese patients the superficialization procedure of the
      venous part of fistula under the skin was performed. RESULTS: In 23 patients of
      this group, an easy and uncomplicated fistula puncturing was achieved. One
      patient had the complication of fistula clotting. CONCLUSION: Subcutaneous
      transposition of the arterialized median antebrachial vein is a simple and
      effective method of an adequate distal native fistula creation in patients with
      deeply located forearm veins.

PMID- 11849473
TI  - Protease mediated tubular injury: a new direction in acute renal failure?

PMID- 11849474
TI  - Can angiotensin II be used for renoprotection?

PMID- 11849475
TI  - When is "aristolochic acid nephropathy" more accurate than "Chinese herbs
      nephropathy"?

PMID- 11849476
TI  - Bone alkaline phosphatase isoforms in chronic renal failure.

PMID- 11849478
TI  - Prediction of hypertension in hemodialysis patients.

PMID- 11849480
TI  - The value of the (1-84) PTH/C-PTH ratio for the diagnosis of low bone turnover in
      dialysis patients.

PMID- 11849482
TI  - Intrarenal mechanisms of salt and water retention in the nephritic syndrome.

PMID- 11849484
TI  - Exposure to non-acid fresh meat decontamination washing fluids sensitizes
      Escherichia coli O157:H7 to organic acids.
AB  - AIMS: To investigate whether Escherichia coli O157:H7 maintains acid tolerance in
      water meat decontamination washing fluids. METHODS AND RESULTS: A rifampicin
      resistant derivative of E. coli O157:H7 strain ATCC 43895 was inoculated (10(5)
      cfu ml(-1)) in spray-washings from meat sprayed with cold (10 degrees C) or hot
      (85 degrees C) water, stored at 10 degrees C for up to 14 days, and its acid
      tolerance was assessed at 2 and 8 days by exposure to broth or new washings
      adjusted to pH 3.5 or 3.7 with lactic or acetic acid. The pathogen survived in
      the water washings, but it was outgrown by the natural, Pseudomonas-like flora,
      and it was sensitized to acid. CONCLUSIONS: The acid tolerance of E. coli O157:H7
      decreases following exposure to non-acid, but otherwise stressful, conditions
      prevailing in water meat washings at 10 degrees C. SIGNIFICANCE AND IMPACT OF THE
      STUDY: These findings suggest that the more intense use of water-based
      technologies should be included in meat decontamination strategies because they
      may contribute to enhanced meat safety by inducing acid sensitization in E. coli
      O157:H7.

PMID- 11849485
TI  - Purification and characterization of a thermostable alkaline protease from
      alkalophilic Bacillus pumilus.
AB  - AIMS: An investigation was carried out on the purification and characterization
      of an alkaline protease from Bacillus pumilus MK6-5. METHODS AND RESULTS: An
      alkalophilic Bacillus pumilus MK6-5 was grown in a laboratory fermenter
      containing 1% reverse osmosis concentrated cheese whey powder, 0.25% corn steep
      liquor, 1% glucose, 0.5% tryptone, 1% sodium citrate, 0.02% MgSO4.7H2O and 0.65%
      Na2CO3 at 35 degrees C and pH 9.6, agitation at 250 rev min(-1) and aeration of 1
      vvm for 60 h. When the enzyme was purified using ammonium sulphate precipitation,
      ion exchange and gel filtration chromatographies, a 26.2% recovery of enzyme with
      36.6-fold purification was recorded. The purified protease was found to be
      homogenous by SDS-PAGE with molecular mass estimate of 28 kDa. The enzyme was
      optimally active at pH 11.5 and temperature of 55-60 degrees C. The Km and kcat
      values observed with synthetic substrates at 37 degrees C and pH 8.0 were 1.1
      mmol l(-1) and 624 s(-1) for Glu-Gly-Ala-Phe-pNA and 3.7 mmol l(-1) and 826 s(-1)
      for Glu-Ala-Ala-Ala-pNA, respectively. The kinetic data revealed that small
      aliphatic and aromatic residues were the preferred residues at the P1 position.
      Inhibition profile exhibited by PMSF suggested the B. pumilus protease to be an
      alkaline serine protease. CONCLUSIONS: Bacillus pumilus MK6-5 produced a calcium
      dependent, thermostable alkaline serine protease. SIGNIFICANCE AND IMPACT OF THE
      STUDY: The thermostable alkaline protease from Bacillus pumilus MK6-5 will be
      extremely useful in ultrafiltration membrane cleaning due to its ability to work
      in broad pH and temperature ranges, and tolerance to detergents, unlike the
      mesophilic proteases which face these limitations.

PMID- 11849486
TI  - Enhanced inactivation of Listeria monocytogenes by nisin in the presence of
      ethanol.
AB  - AIMS: The effect of combinations of nisin and ethanol on the survival of Listeria
      monocytogenes was investigated. METHODS AND RESULTS: Killing by nisin was
      enhanced during simultaneous exposure to ethanol (2-7% v/v). For example, while
      10 IU ml(-1) nisin reduced viability by 1 log unit in 20 min, a combination of
      this antimicrobial peptide and 5% ethanol, reduced numbers of surviving cells by
      3 log units. Increasing the concentrations of either ethanol (2-7%) or nisin (10
      50 IU ml(-1)) led to increased cell death with synergy being demonstrated for all
      combinations tested and at a range of temperatures from 5 to 37 degrees C.
      CONCLUSIONS: Ethanol can act synergistically with nisin to reduce the survival of
      L. monocytogenes. SIGNIFICANCE AND IMPACT OF THE STUDY: Combinations of ethanol
      and nisin may be feasible as an effective way of controlling this pathogen in the
      food processing environment.

PMID- 11849487
TI  - A versatile reactor for continuous monitoring of biofilm properties in laboratory
      and industrial conditions.
AB  - AIMS: The understanding of the dynamics of surface microbial colonization with
      concomitant monitoring of biofilm formation requires the development of biofilm
      reactors that enable direct and real-time evaluation under different hydrodynamic
      conditions. METHODS AND RESULTS: This work proposes and discusses a simple flow
      cell reactor that provides a means to monitoring biofilm growth by periodical
      removing biofilm-attached slides for off-line, both non-destructive and
      destructive biofilm analyses. This is managed without the stoppage of the flow,
      thus reducing the contamination and the disturbance of the biofilm development.
      With this flow cell, biofilm growth and respiratory activity can be easily
      followed, either in well-defined laboratory conditions or in an industrial
      environment. CONCLUSIONS, SIGNIFICANCE AND IMPACT OF THE STUDY: The reproducible
      and typical biofilm development curves obtained, validated this flow cell and
      confirmed its potential for different biofilm-related studies, which can include
      biocidal treatment.

PMID- 11849488
TI  - Antimicrobial effect of essential oils on the seafood spoilage micro-organism
      Photobacterium phosphoreum in liquid media and fish products.
AB  - AIMS: To evaluate the antimicrobial effect of nine essential oils (EO) on P.
      phosphoreum and determine the effect of oregano oil on the shelf-life of modified
      atmosphere-packed (MAP) cod fillets. METHODS AND RESULTS: The antimicrobial
      effect of EO was studied in a liquid medium and in product storage trials. Oils
      of oregano and cinnamon had strongest antimicrobial activity, followed by
      lemongrass, thyme, clove, bay, marjoram, sage and basil oils. Oregano oil (0.05%,
      v/w) reduced growth of P. phosphoreum in naturally contaminated MAP cod fillets
      and extended shelf-life from 11-12 d to 21-26 d at 2 degrees C. CONCLUSIONS:
      Oregano oil reduced the growth of P. phosphoreum and extended the shelf-life of
      MAP cod fillets. SIGNIFICANCE AND IMPACT OF THE STUDY: Mild and natural
      preservation using EO can extend the shelf-life of MAP seafood through inhibiting
      the specific spoilage organism P. phosphoreum.

PMID- 11849489
TI  - Citrulline as the main precursor of ethyl carbamate in model fortified wines
      inoculated with Lactobacillus hilgardii: a marker of the levels in a spoiled
      fortified wine.
AB  - AIMS: The aim of this study was to investigate the production of ethyl carbamate
      (EC) precursors by Lactobacillus hilgardii in model and Douro fortified wines and
      to determine the relationship between these compounds and EC levels in this type
      of wine. METHODS AND RESULTS: Several model fortified wines and fortified wine
      inoculated with L. hilgardii were analysed for citrulline and EC formation. A
      good correlation (R > 0.9) was obtained between citrulline and potential EC (that
      EC which is formed during heating of sample at 80 degrees C for 48 h).
      CONCLUSIONS: This correlation allowed us to calculate the potential EC formed
      during lactic acid bacteria activity in fortified wine. SIGNIFICANCE AND IMPACT
      OF THE STUDY: A good correlation was obtained (R=0.92) between measured and
      calculated EC in spoiled fortified wines, citrulline apparently being the main EC
      precursor produced by Lact. hilgardii thus contributing to the potential EC in
      this type of wine.

PMID- 11849490
TI  - Implementation of real-time PCR to tetrathionate broth enrichment step of
      Salmonella detection in poultry.
AB  - AIMS: The present study describes the implementation of real-time PCR to
      tetrathionate broth enrichment step of Salmonella detection in poultry. METHODS
      AND RESULTS: Real-time PCR with Salmonella invA-specific primers and a standard
      bacteriological method was applied to detect Salmonella in tetrathionate
      enrichment cultures of 492 intestinal homogenates and 27 drag swabs from 47
      poultry flocks. The number of positive individual samples by real-time PCR and
      culture method was 65 (12.5%) and 35 (6.8%), respectively. The number of
      Salmonella-positive flocks was 13 (27.7%) by both methods. PCR detection required
      25 min for up to 32 samples. Melting curve analysis revealed the Tm for
      Salmonella-specific PCR product as 87 +/- 1 degrees C. CONCLUSIONS:
      Implementation of real-time PCR to tetrathionate broth enrichment step reduces
      the Salmonella detection time to 18 h and 25 min. Isolation of Salmonella should
      be carried out with PCR to determine the serovar. SIGNIFICANCE AND IMPACT OF THE
      STUDY: Real-time PCR is a powerful tool in rapid and accurate Salmonella
      monitoring in poultry companies, together with standard bacteriology.

PMID- 11849491
TI  - The symbiosis of Bacillus subtilis L-forms with Chinese cabbage seedlings
      inhibits conidial germination of Botrytis cinerea.
AB  - AIMS: To establish whether germination of Botrytis cinerea was affected by the
      symbiosis of Bacillus subtilis L-form bacteria with Chinese cabbage. METHODS AND
      RESULTS: Germinating seeds of Chinese cabbage were co-cultivated with either L
      forms of Bacillus subtilis or 5% (w/v) mannitol by soaking for 3 h. Seeds were
      then washed in sterile water, sown on a minimal medium and incubated in
      controlled conditions. L-form symbiosis was detected over a time course by ELISA.
      Conidial germination of Botrytis cinerea was significantly reduced on
      cotyledonous leaves of L-form-treated plants compared with controls. CONCLUSIONS:
      Symbiosis of B. subtilis L-form bacteria during seed germination of Chinese
      cabbage inhibits conidial germination in plants on subsequent exposure to
      Botrytis cinerea. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first account
      of plant symbiosis with L-form bacteria showing antagonism to a fungal plant
      pathogen. This has promising implications for the use of this L-form as a
      biocontrol agent.

PMID- 11849492
TI  - Removal of heavy metals by an Aspergillus terreus strain immobilized in a
      polyurethane matrix.
AB  - AIMS: The aim was to investigate the biosorption of chromium, nickel and iron
      from metallurgical effluents, produced by a steel foundry, using a strain of
      Aspergillus terreus immobilized in polyurethane foam. METHODS AND RESULTS: A.
      terreus UFMG-F01 was immobilized in polyurethane foam and subjected to
      biosorption tests with metallurgical effluents. Maximal metal uptake values of
      164.5 mg g(-1) iron, 96.5 mg g(-1) chromium and 19.6 mg g(-1) nickel were
      attained in a culture medium containing 100% of effluent stream supplemented with
      1% of glucose, after 6 d of incubation. CONCLUSIONS: Microbial populations in
      metal-polluted environments include fungi that have adapted to otherwise toxic
      concentrations of heavy metals and have become metal resistant. In this work, a
      strain of A. terreus was successfully used as a metal biosorbent for the
      treatment of metallurgical effluents. SIGNIFICANCE AND IMPACT OF THE STUDY: A.
      terreus UFMG-F01 was shown to have good biosorption properties with respect to
      heavy metals. The low cost and simplicity of this technique make its use ideal
      for the treatment of effluents from steel foundries.

PMID- 11849493
TI  - Exopolysaccharide production from Sclerotium glucanicum NRRL 3006 and
      Botryosphaeria rhodina DABAC-P82 on raw and hydrolysed starchy materials.
AB  - AIMS: Evaluation of fermentative usage of raw starchy materials for
      exopolysaccharide (EPS) production by Sclerotium glucanicum NRRL 3006 and
      Botryosphaeria rhodina DABAC-P82. METHODS AND RESULTS: Non-hydrolysed corn
      starch, soft wheat flour, potato flour, cassava flour, sweet and industrial
      potato flours, and corn starch hydrolysed to different dextrose equivalent (DE)
      were tested in shaken culture for EPS production. Both fungal strains produced
      EPS on all tested materials but the production was maximum on hydrolysed corn
      starch (30.5 and 19.8 g l(-1) by B. rhodina and S. glucanicum on corn starch at
      100 and 62 DE, respectively). CONCLUSIONS: Raw starchy materials as such and, in
      particular, partially or totally hydrolysed corn starch could be used profitably
      for EPS production by S. glucanicum and B. rhodina. SIGNIFICANCE AND IMPACT OF
      THE STUDY: The excellent EPS production, productivity and yield of B. rhodina
      DABAC-P82 when grown on 60 g l(-1) of totally hydrolysed corn starch.

PMID- 11849494
TI  - Mycelial growth and exo-biopolymer production by submerged culture of various
      edible mushrooms under different media.
AB  - AIMS: The effect of synthetic media on the submerged mycelial growth and exo
      biopolymer production in various edible mushrooms was investigated in shake flask
      culture. METHODS AND RESULTS: Among 19 mushrooms examined, the relatively high
      yield in mycelial biomass and exo-biopolymer production was achieved in potato
      malt peptone (PMP) medium. In particular, Ganoderma lucidum NO. 1 and Phellinus
      linteus KCTC 6190 showed favourable growth in PMP medium with exo-biopolymer
      concentration of 1170 and 1520 mg l(-1), respectively. CONCLUSIONS: Enhanced exo
      biopolymer production was achieved from Ganoderma lucidum NO. 1 and Phellinus
      linteus KCTC 6190 in a 5L batch fermentor, indicating approximately 5000 and 2410
      mg l(-1), respectively. SIGNIFICANCE AND IMPACT OF THE STUDY: The exo-biopolymer
      production and mycelial growth from various mushrooms were found to be strongly
      controlled by different complex media.

PMID- 11849495
TI  - Development of membrane filter holder (MFH) method for recovery of heat-injured
      Escherichia coli O157:H7 and Salmonella typhimurium.
AB  - AIMS: A method of recovering sublethally heat-injured bacteria was developed with
      specific apparatus (membrane filter holder; MFH) which was originally used for
      Iso-Grid Hydrophobic membrane. filter holder. METHODS AND RESULTS: The procedure
      used a non-selective agar underlayed with a selective medium with a MFH. A non
      selective agar was poured on upper part (compartment A) of MFH, and then injured
      foodborne pathogens were inoculated on the non-selective medium. After 3-h repair
      incubation period, selective agar was added to the bottom of the chamber
      (compartment B) of the MFH and further incubated. By diffusing through the non
      selective top agar, selective agents from the underlay medium impart selectivity
      to the system. CONCLUSIONS: Using the MFH method, recovery of heat-injured
      foodborne pathogens (Escherichia coli O157:H7 and Salmonella typhimurium) were
      not different (P > 0.05) from recoveries with non-selective media (TSA). However,
      the recoveries of foodborne pathogens on MFH were significantly higher (P < 0.05)
      than those of direct plating on selective medium such as SMAC (MacConkey Sorbitol
      Agar) or XLD (Xylose Lysine Desoxycholate). SIGNIFICANCE AND IMPACT OF THE STUDY:
      In conclusion, the MFH method is a simple and convenient method for recovery of
      heat-injured foodborne pathogens.

PMID- 11849496
TI  - Production of Aspergillus terreus alpha-L-rhamnosidase by solid state
      fermentation.
AB  - AIMS: The study of production of Aspergillus terreus CECT 2663 alpha-L
      rhamnosidase in solid state fermentation using wheat bran, washed sugar cane
      bagasse and polyurethane foam as substrates or supports for the enzyme
      production. METHODS AND RESULTS: Cultures were carried out in Petri dishes under
      controlled temperature and humidity. Naringin or rhamnose were the enzyme
      inducers and carbon sources. The enzyme activity to inducer ratio was appreciably
      greater when using sugar cane bagasse or polyurethane foam than wheat bran. The
      influence of inoculum size, inducer, airflow, humidity and temperature were
      determined. Under optimum conditions, about four units of enzyme per ml nutrient
      solution were obtained after 4-6 d. CONCLUSIONS: The activity to inducer ratio
      was higher, and the cultivation time was shorter in solid state fermentation than
      those observed in submerged cultures. SIGNIFICANCE AND IMPACT OF THE STUDY: Solid
      cultures, using naringin as inducer, can be appropriate alpha-L-rhamnosidase
      production.

PMID- 11849497
TI  - Survival of Campylobacter jejuni on beef trimmings during freezing and frozen
      storage.
AB  - AIMS: To investigate the survival of two animal isolates of Campylobacter jejuni
      on beef trimmings during freezing and frozen storage. METHODS AND RESULTS: Meat
      packs inoculated with 10(3) or 10(6) cfu g(-1) of either strain of C. jejuni were
      frozen to -18 degrees C, and sampled at regular intervals over 112 d storage to
      determine Campylobacter numbers and sublethal injury. For both strains and
      inoculation levels the numbers of Campylobacter decreased in the first 7 d of
      storage by ca. 0.6-2.2 log cfu g(-1) and then remaining constant over the
      remainder of the storage trial, with neither isolate exhibiting sublethal injury.
      CONCLUSIONS: Despite an initially significant decrease in number, these pathogens
      were able to survive standard freezing conditions in meat, but did not exhibit
      sublethal injury. SIGNIFICANCE AND IMPACT OF THE STUDY: Strict hygiene and/or the
      implementation of decontamination technologies are recommended as a means to
      assure the safety of meat with respect to this pathogen.

PMID- 11849498
TI  - Bacteriocin production by spray-dried lactic acid bacteria.
AB  - AIMS: Cell survival and antagonistic activity against Listeria innocua, Listeria
      monocytogenes and Staphylococcus aureus were investigated after spray-drying
      three bacteriocin-producing strains of lactic acid bacteria: Carnobacterium
      divergens, Lactobacillus salivarius and Lactobacillus sakei. METHODS AND RESULTS:
      Bacterial cell concentrates were spray-dried and stored at 4 degrees C and 18
      degrees C and 0.3% ERH (equilibrium relative humidity). Enumeration and
      antagonistic activity were evaluated before and after spray-drying and at regular
      intervals during storage. CONCLUSIONS: A higher survival rate was obtained when
      survival was performed at 4 degrees C. With the exception of Carnobacterium
      divergens which lost the inhibitory activity against Staph. aureus after drying,
      antagonistic production was not affected by the process nor by the storage. Of
      the three species studied, Lact. salivarius showed the highest resistance to the
      spray-drying and storage processes. SIGNIFICANCE AND IMPACT OF THE STUDY: Spray
      drying is a potentially useful process for large scale production of dried
      powders containing viable organisms with antagonistic activity against pathogens.

PMID- 11849499
TI  - Random amplified polymorphic DNA analysis for differentiation of Leuconostoc
      mesenteroides subspecies isolated from Tenerife cheese.
AB  - AIMS: In the present study, a RAPD-PCR fingerprinting method was developed to
      assign Tenerife cheese Leuconostoc mesenteroides strains to its three subspecies
      (mesenteroides, cremoris and dextranicum). METHODS AND RESULTS: Arbitrarily
      primed-PCR gave different DNA banding patterns for each type strain of Leuc.
      mesenteroides subspecies consisting in three major and intense bands of: 1800,
      1600 and 1150 bp for subspecies mesenteroides 1800, 1150 and approximately 350 bp
      for subspecies cremoris; and 1800, 1600 and 1500 bp for subspecies dextranicum.
      DNA fingerprints of Tenerife cheese Leuc. mesenteroides subspecies were
      coincident to that of their respective type strain. RAPD profiles were
      reproducible with DNA template obtained by two different extraction methods.
      CONCLUSIONS: Tenerife cheese Leuc. mesenteroides strains were rapidly and
      unequivocally assigned to one of the subspecies by comparing their RAPD-PCR
      fingerprints with those displayed by type strains used as standards. This
      technique can be applied to complement preliminary identification of Leuc.
      mesenteroides to the species level by other molecular methods such as protein
      fingerprinting. SIGNIFICANCE AND IMPACT OF THE STUDY: RAPD-PCR allows reliable,
      reproducible and rapid molecular differentiation of Tenerife cheese Leuc.
      mesenteroides subspecies with no need to use time-consuming and often ambiguous
      biochemical tests.

PMID- 11849500
TI  - A rapid staining technique for the detection of the initiation of germination of
      bacterial spores.
AB  - AIMS: We propose to apply the Wirtz-Conklin staining technique to evaluate spore
      germination. METHODS AND RESULTS: Spores at different stages of germination were
      stained with modified spore stain (Wirtz-Conklin) and evaluated for staining
      properties. Bacillus spores suspended in deionized water, which does not support
      germination, stained greenish-blue. Spores suspended in germination enhancers
      that did not form bacilli stained pink, indicating the initiation of germination.
      Spores suspended in culture media, which promotes bacterial outgrowth, formed
      bacilli and were also stained pink. CONCLUSIONS: Modified spore stain (Wirtz
      Conklin) was found to be useful to detect the initiation of spore germination as
      early as 30 min following incubation in a germination environment. SIGNIFICANCE
      AND IMPACT OF THE STUDY: This simple staining procedure is useful in detecting
      the initiation of germination of bacterial spores.

PMID- 11849501
TI  - Cuticle-degrading proteases from the entomopathogen Metarhizium flavoviride and
      their distribution in secreted and intracellular fractions.
AB  - AIMS: The aim of this study was to analyse a native isolate of Metarhizium
      flavoviride (CG423) which is being developed as a myco-insecticide against
      grasshoppers in Brazil for the production of the cuticle-degrading subtilisin
      like (Pr1), and trypsin-like (Pr2) proteases. METHODS AND RESULTS: The results
      show that Pr1 activity occurred only in medium supplemented with grasshopper
      cuticle (Schistocerca pallens). In contrast, Pr2 was detected in higher amounts
      on defined growth substrate than on cuticle-supplemented medium. Both activities
      were detected after 48 h of growth, suggesting that in S. pallens cuticle
      containing medium these protease types are not co-ordinately expressed. Low
      levels of enzyme activity were detected when pre-grown mycelium was used to
      investigate the induction of Pr1 proteases. CONCLUSIONS: The analysis of Pr1 and
      Pr2 distribution in both secreted and intracellular fractions revealed high
      percentage of extracellular activity, which may suggest the occurrence of an
      efficient mechanism of protein secretion by this fungus, probably related to
      substrate degradation which provides nutrients for fungal growth.

PMID- 11849502
TI  - (1-->6)-Beta-D-glucan as the cell wall binding site for Debaryomyces hansenii
      killer toxin.
AB  - AIMS: The aims of this study were to characterize the cell wall binding site of
      Debaryomyces hansenii killer toxin to provide a simple purification method and to
      determine some characteristics of this toxin. METHODS AND RESULTS: Various linear
      (1-->6)-beta-D-glucans of different origins were effective competitive inhibitors
      of the toxin action. Periodate oxidation and 1H-NMR was used to determine the
      receptor nature. Affinity chromatography on pustulan-Sepharose column was used to
      purify D. hansenii killer toxin, probably a 23-kDa protein. The killer toxin
      character was cureless. CONCLUSIONS: The investigation revealed that the killer
      toxin was mainly adsorbed by (1-->6)-beta-D-glucans. This is a low molecular
      weight protein, probably encoded by chromosomal genes. SIGNIFICANCE AND IMPACT OF
      THE STUDY: The specificity of the killer toxin for its receptor provides an
      effective means to purify the killer toxin. This study is the first to identify
      the cell wall binding site of this killer toxin, a toxin with properties of
      industrial relevance.

PMID- 11849503
TI  - Long-term survival of Escherichia coli O157 on pasture following an outbreak
      associated with sheep at a scout camp.
AB  - AIMS: To monitor the decay of E. coli O157 in soil (loamy sand) on a scout
      campsite following an outbreak in humans. METHODS AND RESULTS: Samples of soil
      and sheep faeces were collected from the campsite and tested for the presence of
      E. coli O157 by immunomagnetic separation (IMS) after enrichment in buffered
      peptone water + vancomycin at 42 degrees C for 6 h. Enumeration of target was
      carried out by direct plating onto sorbitol MacConkey agar plates supplemented
      with cefixime and tellurite (CTSMAC) incubated at 37 degrees C for 24 h. Low
      numbers (< 100 g(-1)) were estimated by the most probable number (3-tube MPN)
      technique. CONCLUSIONS: Survival was observed for 15 weeks. SIGNIFICANCE AND
      IMPACT OF THE STUDY: A number of laboratory studies have followed the decay of E.
      coli O157 in soil, animal faeces and water. This study follows (for the first
      time) the decay of the organism in soil after an outbreak associated with sheep.
      It demonstrates the long-term persistence of the organism in the environment and
      the results will be potentially important in performing risk assessments for both
      human and animal infection.

PMID- 11849504
TI  - Comparison of faecal Lactobacillus populations in experimental animals from
      different breeding facilities and possible consequences for probiotic studies.
AB  - AIMS: The effect of probiotic lactobacilli is likely dependent on the indigenous
      Lactobacillus strains in the intestinal tract. Since a substantial number of
      probiotic studies is performed in rodents, we compared the Lactobacillus strains
      of different rat and mouse populations in three animal facilities. METHODS AND
      RESULTS: SDS-PAGE and 16S rDNA analysis of cultured faecal lactobacilli revealed
      that different Lactobacillus strains were detected in genetically similar Wistar
      rats bred at different locations. Further, within the same animal facility host
      genetics did not affect the types of the predominant lactobacilli strains.
      CONCLUSIONS: Our results show that the environmental background of laboratory
      animals rather than host genetics determines the indigenous Lactobacillus strains
      that are found. SIGNIFICANCE AND IMPACT OF THE STUDY: Our findings underline the
      importance of microflora analysis in probiotic studies.

PMID- 11849505
TI  - Interference between enterovirus and reovirus as a limiting factor in
      environmental virus detection.
AB  - AIMS: Faecal material from raw sewage or other sources lacking effective
      treatment sometimes contaminates water for human consumption. The relevant
      Italian regulations therefore call for testing drinking and recreational water
      for the presence of enterovirus. METHODS AND RESULTS: Traditional methods of
      analysis are based on revealing the typical cytopathic effects of enterovirus on
      cell cultures. However, the presence in environmental samples of different types
      of virus may cause interference phenomena that mask such cytopathic effects. The
      paper reports on an experimental test of this interference hypothesis. Buffalo
      Green Monkey cell cultures were co-infected via mixed suspensions of the polio
      type 3 virus and reovirus type 1. Cytopathic effects were then sought and the
      presence of enterovirus tested for via RT-PCR. CONCLUSIONS, SIGNIFICANCE AND
      IMPACT OF THE STUDY: The results obtained indicate that the normally high
      sensitivity of tests for the detection of enterovirus in samples is considerably
      decreased by the simultaneous presence of reovirus.

PMID- 11849506
TI  - Nisin and pediocin production on mussel-processing waste supplemented with
      glucose and five nitrogen sources.
AB  - AIMS: Optimization of bacteriocin production by L. lactis subsp. lactis CECT 539
      and Ped. acidilactici NRRL B-5627 on mussel-processing wastes. METHODS AND
      RESULTS: The concentrations of glucose and five nitrogen sources that optimize
      nisin and pediocin production were determined using a second order orthogonal
      factorial design. NH4Cl, glycine and glutamic acid were poor nitrogen sources.
      Enhanced pediocin and nisin productions were achieved in a medium supplemented
      with yeast extract or Bacto casitone. CONCLUSIONS: Mussel-processing wastes could
      be successfully used as a culture medium for bacteriocin production at low
      production cost. SIGNIFICANCE AND IMPACT OF THE STUDY: Average optimization led
      to a threefold increase in pediocin production (from 322 to 934 BU ml(-1)) and in
      nisin production (from 32 to 100 BU ml(-1)) when compared with the unsupplemented
      medium. For this reason, mussel-processing waste warrants further investigation
      due to its potential use as a cheap culture medium for upscaling bacteriocin
      production.

PMID- 11849507
TI  - Expression and processing of a major xylanase (XYN2) from the thermophilic fungus
      Humicola grisea var. thermoidea in Trichoderma reesei.
AB  - AIMS: To express a gene encoding a heterologous fungal xylanase in Trichoderma
      reesei. METHODS AND RESULTS: Humicola grisea xylanase 2 (xyn2) cDNA was expressed
      in Trichoderma reesei under the main cellobiohydrolase I (cbh1) promoter (i) as a
      fusion to the cellobiohydrolase I (CBHI) secretion signal and (ii) the mature
      CBHI core-linker. The recombinant xylanase (HXYN2) was secreted into the
      cultivation medium and processed in a similar fashion to the endogenous T. reesei
      xylanases, resulting in an active enzyme. CONCLUSIONS, SIGNIFICANCE AND IMPACT OF
      THE STUDY: HXYN2 was successfully processed in T. reesei. Composition of the
      culture medium affected the HXYN2 yields, favouring Avicel-lactose as a carbon
      source. Best yields (about 0.5 g l(-1)) in shake flask cultivations were obtained
      from a transformant where xyn2 was fused directly to the CBHI secretion signal.

PMID- 11849508
TI  - Evaluation of selective media for Campylobacter isolation when cycloheximide is
      replaced with amphotericin B.
AB  - AIMS: Laboratory media for the isolation of Campylobacter usually contain various
      selective agents, designed to allow these bacteria to grow whilst suppressing
      that of other organisms. For example, cycloheximide has often been incorporated
      into Campylobacter media to inhibit the growth of fungi. The production and
      availability of cycloheximide, however, has recently decreased due to concerns
      relating to its potential toxicity for mammalian cells and the compound has also
      become more expensive as a result. An alternative antifungal agent is necessary,
      and to address this, the effect of using amphotericin B in place of cycloheximide
      in Campylobacter selective broths and agars was examined. METHODS AND RESULTS:
      The growth of Campylobacter strains and the suppression of potential competitor
      organisms in selective broths or on selective agars containing either
      amphotericin B or cycloheximide was quantified, using pure microbial cultures.
      The results were then confirmed by testing food and water samples that contained
      high levels of micro-organisms, including Campylobacter. CONCLUSIONS: The results
      of this study indicate that amphotericin B is a suitable replacement for
      cycloheximide in Campylobacter selective media.

PMID- 11849509
TI  - In-well cell lysis technique reveals two new megaplasmids of 103.0 and 212.6 MDa
      in the multiple plasmid-containing strain V517 of Escherichia coli.
AB  - AIMS: Identification of two new plasmids in the multiple plasmid-containing
      strain V517 of Escherichia coli. METHOD AND RESULTS: By using an in-well mild
      cell lysis technique suitable for megaplasmids observation, two plasmids of 103.0
      and 212.6 MDa were detected in the multiplasmid-containing E. coli V517.
      CONCLUSIONS: The two new megaplasmids that were completely overlooked when
      standard disruptive procedures were used, can now be added to the list of eight
      plasmids with molecular size from 1.36 to 35.84 MDa reported earlier.
      SIGNIFICANCE AND IMPACT OF THE STUDY: This finding allows to use the strain V517
      not only as a size reference of small and moderately large plasmids but as a size
      reference of megaplasmids as well.

PMID- 11849510
TI  - Comparison of the acidifying activity of Lactococcus lactis subsp. lactis strains
      isolated from goat's milk and Valdeteja cheese.
AB  - AIMS: This work was carried out to study the acid production by Lactococcus
      lactis subsp. lactis strains isolated from goat's milk and goat cheese (Valdeteja
      variety) in order to select a suitable starter culture for industrial goat cheese
      manufacturing. METHODS AND RESULTS: The titrable acidity of 45 Lactococcus lactis
      subsp. lactis strains isolated from a home-made batch of Valdeteja cheese with
      excellent sensory characteristics was measured over a period of 18 h. The strains
      were divided into two groups depending on the acid production rate: 20 fast acid
      producer (F) strains and 25 slow acid producer (S) strains. The kinetic
      parameters (lag phase, maximum acid production rate and value of upper asymptote
      curve) of the acid production curves for F and S strains were significantly (P <
      0.001) different. CONCLUSIONS: Significant (P < 0.001) differences between
      titrable acidity of F and S strains were observed after the second hour of
      incubation. SIGNIFICANCE AND IMPACT OF THE STUDY: An F strain acetoin producer
      (Lactococcus lactis subsp. lactis 470Ch2) was selected as autochthonous starter
      culture for industrial Valdeteja goat cheese manufacturing.

PMID- 11849511
TI  - The ineffectiveness of organic acids, freezing and pulsed electric fields to
      control Escherichia coli O157:H7 in beef burgers.
AB  - AIMS: The objective of this study was to investigate the potential value of
      individual and combined applications of some GRAS (generally regarded as safe)
      additives with freezing and pulsed electric field (PEF) application, in reducing
      the risks associated with the presence of E. coli O157:H7 in beef burgers.
      METHODS AND RESULTS: Beef burgers, trimmings and filter paper were inoculated
      with E. coli O157:H7 and subjected to a range of chemical and physical
      treatments. Sequential application of 2% (v/v) lactic acid and freezing (at - 20
      degrees C for 2 h) resulted in a decrease of approximately 6 log10 cfu cm(-1) in
      E. coli O157:H7, but only on filter paper. All other treatments were ineffective.
      CONCLUSIONS: Currently available methods for controlling E.coli O157:H7 in beef
      burgers during production are ineffective. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Further research is needed to develop controls for E. coli O157:H7 during beef
      burger production.

PMID- 11849512
TI  - Identification of Fusarium graminearum in cereal samples by DNA Detection Test
      Strips.
AB  - AIMS: Development of a fast, sensitive and easy to handle method for the
      detection of Fusarium graminearum contamination in cereal samples by PCR. METHODS
      AND RESULTS: DNA Detection Test Strips were used for PCR-product detection and
      the method was compared to agarose gel electrophoresis. A minimum of 0.26 ng of
      purified target DNA was detectable with the Test Strip Detection limit in less
      contaminated samples was slightly lower when gel electrophoresis was used for
      amplicon detection. In highly contaminated samples, detection limits of both
      methods were similar. CONCLUSIONS: Detection of PCR products was performed in 20
      min without the need of special technical equipment or hazardous fluorescent DNA
      dyes. SIGNIFICANCE AND IMPACT OF THE STUDY: The new method described is useful
      for the screening of cereals in industrial quality control.

PMID- 11849513
TI  - Antimicrobial resistance and plasmid profiles of Campylobacter jejuni and
      Campylobacter coli from human and animal sources.
AB  - AIMS: The purpose of this study was to determine the susceptibility of
      Campylobacter jejuni and Campylobacter coli isolates to antimicrobial agents and
      to investigate the presence of plasmid DNA. METHODS AND RESULTS: A total of 15
      clinical isolates from children faeces, and 29 animal isolates of Campylobacter
      jejuni (n=22) and Campylobacter coli (n=22) were tested for susceptibility to 9
      antimicrobial agents using a disc diffusion method, and screened for the presence
      of plasmid DNA by agarose gel electrophoresis. Of the 44 isolates, 56.8% were
      resistant to sulphonamide, 25% to norfloxacin, 18.2% to erythromicin,
      ciprofloxacin and ampicillin, and 13.6% to tetracycline. All isolates were
      susceptible to gentamicin, chloramphenicol and cefotaxime. Plasmids were detected
      in one Camp. jejuni (4.54%) strain isolated from sheep and in six (27.27%) Camp.
      coli strains isolated from rhesus monkey(3), swine(2), and poultry(1) with sizes
      ranging from 3.4 to 50 kb. CONCLUSIONS: The majority of the human isolates were
      susceptible to antibiotics commonly used for the treatment of campylobacteriosis.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The origin and spread of Campylobacter
      resistance to antibiotics are discussed, with particular respect to the current
      situation in Brazil.

PMID- 11849515
TI  - The first year of doctoring: still a survival exercise.

PMID- 11849517
TI  - No-one forgets a bad teacher.

PMID- 11849518
TI  - Is medical postgraduate certification improving health outcomes?

PMID- 11849519
TI  - Pre-registration house officers and ward-based learning: a 'new apprenticeship'
      model.
AB  - INTRODUCTION: The pre-registration house officer (PRHO) year can be seen as a
      formal apprenticeship into the profession of medicine, and as central to the
      identity construction of the doctor. The year characteristically involves
      rotation between specialties, including attachment to ward-based 'firms', where
      consultants teach PRHOs. DISCUSSION: Teaching and learning in ward-based
      environments is under-researched, and the current literature displays a bias
      towards a psychological model of pedagogy that focuses upon transmission of
      knowledge and skills from one individual to another. Such a model offers a
      necessary, but not sufficient, explanation of how work-based learning occurs.
      Understanding the PRHO apprenticeship year should include reference to cultural
      dimensions to learning, especially socialisation into the profession. This
      constitutes an 'extended' (or 'hidden') curriculum model that may be theorised
      through contemporary ideas of activity learning within a 'new apprenticeship'
      framework. CONCLUSION: The dominant psychological model can lead to an
      expectation for a uniform method of teaching and learning in ward round contexts
      that (a) ignores important differences in educational climate between established
      communities of practice, and (b) orients both teachers and learners to one-to-one
      transmission and reception, rather than sensitising to how knowledge may be held
      across members of a working group. The latter shifts emphasis away from reception
      to issues of active access. PRHOs, as novices, are not relegated to passive
      learning roles, but may actively co-construct knowledge with experts, offering
      potential transformation of the practices of ward groups.

PMID- 11849520
TI  - Perceptions of how well graduates are prepared for the role of pre-registration
      house officer: a comparison of outcomes from a traditional and an integrated PBL
      curriculum.
AB  - INTRODUCTION: Most medical schools in the UK have been engaged in major
      curriculum reform based on their premises of what might improve undergraduate
      medical education. In 1994 the course at the medical school of the University of
      Manchester changed to an integrated course using problem-based learning
      throughout and with increased emphasis on community-based medical education. This
      study explores whether the new curriculum has produced any differences in
      perceptions of how well graduates are prepared for the role of pre-registration
      house officer. METHODS: A postal questionnaire was used to survey 1998 Manchester
      graduates (traditional course) and 1999 Manchester graduates (new course), three
      months into their first pre-registration house officer placement. A similar
      questionnaire was sent to the educational supervisors who were supervising the
      graduates. The questionnaire was designed to measure perceptions of levels of
      preparedness for the role of pre-registration house officer, using a list of
      broad areas of competence and specific skills listed in the General Medical
      Council's 'The New Doctor'. RESULTS: Graduates rated the new course significantly
      more effective for 12 of the 19 broad competences and eight of the 13 specific
      skills that were listed. The 'new' graduates rated their understanding of disease
      processes lower than the 'traditional' graduates, but there was no difference in
      the ratings given by the educational supervisors for this. Overall the
      educational supervisors rated the new course as better preparing graduates in
      five of the competences. CONCLUSIONS: Overall, the evaluation shows that a major
      change in curriculum approach has changed the profile of the perceived
      preparedness of graduates for entering professional practice.

PMID- 11849521
TI  - The relationship between pre-registration house officers and their consultants.
AB  - CONTEXT: Previous studies have drawn attention to the importance of the
      trainee/trainer relationship in determining job satisfaction and motivation to
      learn. OBJECTIVES: To study the relationship between pre-registration house
      officers and their consultants through exploring an interpersonal exchange and
      the emotional context in which the exchange took place. To consider any
      association between the type of relationship implied and the trainee's attitude
      to their career. DESIGN: Postal questionnaire covering a wide range of issues.
      This study focused on an open question about a significant or interesting
      exchange, followed by supplementary questions exploring the emotional context of
      the exchange. SETTING: 336 hospitals throughout the United Kingdom. SUBJECTS: A
      cohort of doctors were followed from the time of their application to medical
      school, and studied towards the end of their pre-registration year (n=2456).
      RESULTS: The response rate to the questionnaire was 58.4%. Responses were
      categorised as Support and supervision; Unreasonable behaviour; Consultant
      fallibility; Fair criticism and No exchange. Over half the responses described an
      interaction that made them feel positive. Trainees particularly appreciated
      positive feedback, clinical support, teaching, career advice, patronage, or
      social interaction. The importance of formal appraisal or review sessions in
      providing the setting for a positive exchange was confirmed. Positive
      interactions were associated with a positive view of medicine as a career. A
      minority described an interaction that was negative, involving unreasonable
      demands, criticism (whether perceived as fair or unfair), humiliation, or sexism.
      These were associated with a more negative view of medicine as a career, and of
      themselves as doctors.

PMID- 11849523
TI  - Senior house officers' experience of a six month post in a hospice.
AB  - BACKGROUND: Hospices provide care for patients with a terminal prognosis--a very
      small number of hospices employ Senior House Officers. METHOD: A survey was
      carried out to determine the experiences of SHOs working in hospices and their
      perceptions of the learning opportunities available. Perceived stress was
      measured by a Visual Analogue scale and psychological distress by the GHQ 12.
      RESULTS: Of the 38 posts identified 23 SHOs (60%) responded and the majority had
      qualified during the last five years. Formal teaching was limited, but
      experiential teaching was very positively described. Many SHOs described their
      posts as stressful and cited staff conflict and caring for young patients as
      particularly stressful. Median stress scores as measured on the VAS was 55 mm
      (range 0-98 mm). Five respondents 22% scored for identifiable psychological
      distress on the GHQ 12. CONCLUSION: Conclusions include the need to acknowledge
      the important learning opportunities provided within hospices but also the need
      for consultant staff to be aware of the sources of stress for SHOs and their need
      for support.

PMID- 11849522
TI  - How consultants, hospitals, trusts and deaneries affect pre-registration house
      officer posts: a multilevel model.
AB  - OBJECTIVE: To examine variation in reported quality and working conditions of pre
      registration house officer (PRHO) posts. To use multilevel modelling to determine
      how much of the variation was due to the effects of consultant firms, hospitals,
      trusts and deaneries, as well as variation at the level of the individual doctor.
      DESIGN: Questionnaire survey of national sample of PRHOs at the end of the pre
      registration year. Multilevel modelling was carried out using MLwiN. SETTING:
      PRHOs working in UK approved medical and surgical posts in NHS hospitals from
      August 1996 to January 1999. PARTICIPANTS: One thousand, four-hundred and thirty
      five PRHOs who had previously been part of an extended cohort study of medical
      student selection and training. They reported on a total of 4926 posts, on 2721
      identifiable consultant firms, in 336 hospitals, in 264 trusts and in 17
      deaneries. MAIN OUTCOME MEASURES: PRHOs' perceptions of the overall quality of
      all PRHO posts they had worked in, and working conditions in the current post.
      RESULTS: Twenty percent of PRHO posts were described as excellent and 34% as very
      good, through to 6% reported as not very good, poor or bad. The overall rating of
      the post showed highly significant variation at the level of hospital/trust, and
      consultant firm. Other aspects of posts, such as working conditions showed
      variation at the level of deanery, trust, hospital and firms, with different
      patterns for the different measures. Assessments of stress in PRHOs (GHQ,
      burnout, response to uncertainty), and a desire to leave medicine, showed no
      variation at the level of deanery, trust, hospital or firm. CONCLUSION: Some
      aspects of a PRHO post, in particular overall rated quality, but also many
      aspects of working conditions, show substantial variation at the level of
      hospital, trust and consultant firm, suggesting that differences reflect local
      variation in working practices and treatment of PRHOs, with the possibility of
      change and improvement. The lack of any variation at the level of deanery, trust,
      hospital or firm in stress of PRHOs suggests that these responses are
      idiosyncratic, individual responses by doctors themselves, rather than a general
      characteristic of posts, hospitals, trusts or deaneries.

PMID- 11849524
TI  - Making and sharing decisions about management with patients: the views and
      experiences of pre-registration house officers in general practice and hospital.
AB  - OBJECTIVES: To explore the views and experiences of pre-registration house
      officers (PRHOs) in general practice and hospital settings regarding the concept
      of patient partnership and their experience of involving patients in management
      decisions. DESIGN: The 12 PRHOs who had graduated from British universities and
      who were working within the Yorkshire Deanery were interviewed towards the end of
      their four-month general practice attachments. The interviews were semi
      structured and analysed qualitatively. RESULTS: Three major themes emerged. The
      PRHOs perceived differences in approach between consultations carried out in
      hospital and primary care settings, with general practitioners being more likely
      to share information and decisions with patients. As medical students, the PRHOs
      had little opportunity to practise sharing information and management decisions
      with patients, and variable experience of this after graduation. On the whole
      they were favourable to the concept of patient partnership. CONCLUSIONS: Medical
      students and PRHOs lack training and opportunities to decide on management and
      discuss this with patients and yet, particularly in general practice settings,
      they have to practise these skills. The PRHOs had begun to develop strategies to
      decide how much information to give to patients and to what extent to involve
      patients in management decisions. This is an area that needs further
      consideration when planning both undergraduate and postgraduate medical
      education.

PMID- 11849525
TI  - Stressful incidents, stress and coping strategies in the pre-registration house
      officer year.
AB  - CONTEXT: Previous studies have drawn attention to the stresses experienced by
      doctors in their first year. OBJECTIVES: To gain a deeper understanding of the
      causes of stress in newly qualified doctors, how they cope, and what
      interventions might make the year less traumatic. DESIGN: Postal questionnaire.
      This study focused on an open question asking about a stressful incident, the
      coping strategy used to deal with it, stressors in general and current levels of
      stress using the General Health Questionnaire. SETTING: 336 hospitals throughout
      the United Kingdom. SUBJECTS: A cohort of doctors followed from the time of their
      application to medical school, studied towards the end of their pre-registration
      year (n=2456). RESULTS: The response rate to the questionnaire was 58.4%. The
      incidents were categorised into the major groups Responsibility (33.6%),
      Interpersonal (29.7%), Overwork (17.0%), Death and disease (13.0%), and Self
      (6.7%). GHQ revealed psychological morbidity in 31% of respondents. Stress levels
      were highest in those reporting an incident about Responsibility or Self, lowest
      in those describing Death or disease. Stressors in general and preferred coping
      strategies differed between the groups. CONCLUSION: The incidents suggested the
      following interventions to reduce stress: better supervision in the first few
      weeks in post, at night, and for medical problems on surgical wards; more
      attention to avoiding sleep deprivation; more time for discussion with colleagues
      at work; more personal time with friends and family. The choice of incident
      described was influenced by the personal characteristics of the respondent.

PMID- 11849527
TI  - Are medical postgraduate certification processes valid? A systematic review of
      the published evidence.
AB  - OBJECTIVE: To collate the published works on validation of assessments used in
      postgraduate medical certification. DESIGN: Systematic review of original papers
      on reliability and validity of assessments used in medical postgraduate
      certification. SETTING: Medical and education research databases. RESULTS: Fifty
      five papers were identified from 1985 to 2000. A wide range of approaches to
      validation were employed. Inter-rater reliability and internal consistency were
      the most reported foci for validation. There were just two papers on
      consequential validity, and only a few on construct validity. These two forms of
      validity are considered central in recent general education writing. The majority
      of papers were from general and family practice. There was a noticeable lack of
      papers from the UK Royal Colleges (except the Royal College of General
      Practitioners), despite 5 years of the new unified grade and the renewed emphasis
      on the role of the Royal Colleges in setting assessment criteria. CONCLUSIONS:
      There is a relative scarcity of published papers on validation of assessment for
      postgraduate medical certification considering the influence these high stakes
      processes have on doctors career progression and employment opportunities.
      General and family practice institutions in a number of English speaking
      countries have set an example to others, by showing that rigour and transparency
      in assessment development and implementation can be reflected in publication.

PMID- 11849526
TI  - Anxiety and depression in the first year of medical residency training.
AB  - OBJECTIVE: To perform a screening, follow-up and comparative evaluation of
      depression and anxiety symptoms in a group of 59 first-year internal medicine
      residents of a teaching hospital and evaluate the influence of their rotation,
      nature of rotation, subgroup, sex and the time of year on these symptoms.
      METHODS: We used the Spielberger State-Trait Anxiety Inventory (STAI) and the
      Beck Depression Inventory (BDI), applied seven times, in the last week of every
      rotation. RESULTS AND CONCLUSION: We obtained two identical averages (P=0.98) of
      trait-anxiety, six months apart one from the other. There was a significant
      correlation (R=0.65, P < 0.001) between the indexes of state-anxiety and
      depression. Women had higher levels of symptoms of both anxiety and depression (P
      < 0.001) compared to men. A cluster of three subgroups of residents with higher
      trait-anxiety levels (P=0.001) also showed significantly higher levels of
      symptoms of state-anxiety and depression (P < 0.001). The time of the year and
      the nature of the rotation (emergency or not) did not interfere with the levels
      of depression (P=0.47). We detected rotations where there was greater frequency
      of residents with symptoms compatible with moderate and severe depression. There
      were 2.1% of residents with symptoms compatible with severe, 4.2% with moderate
      and 27% with mild depression. It was possible to graduate symptoms of anxiety and
      depression in residents, evaluate factors involved in their genesis and locate
      residents with moderate and severe depression.

PMID- 11849528
TI  - Facing the challenges of competency-based assessment of postgraduate dental
      training: Longitudinal Evaluation of Performance (LEP).
AB  - CONTEXT: The evaluation of competence in the health professions is of great
      importance to the public and professionals alike. Recent efforts to design
      dependable and accurate systems of assessment for demanding clinical roles are
      increasingly attempting to focus on all-round competence of practitioners. Many
      challenges are faced in this field as a balance between robust assessment
      methodology and feasibility in practice is crucial to implementation and
      adoption. OBJECTIVES: The authors discuss some of the challenges faced by
      educators and clinicians involved in the development of systems of assessment for
      the health professions, and describe a method which aims to address these issues
      in the assessment of postgraduate dental training in Scotland. DISCUSSION: Three
      of the major challenges facing educators and clinicians involved in the design of
      competency-based systems of assessment are considered: the requirement for
      evaluation in different areas of competence; the importance of association of
      assessment with the training objectives, and the types and focus of the
      assessment introduced. Issues around the use of formative and summative
      assessment, and the perception that these must always remain completely separate,
      are discussed in detail. SOLUTIONS: A proposal is made for the introduction of a
      method of assessment which has been designed keeping these challenges in mind.
      The rationale behind this assessment method is described.

PMID- 11849530
TI  - SHO training in Northern Ireland.

PMID- 11849531
TI  - Medical student debt in the UK.

PMID- 11849532
TI  - Formation of D-alanyl-lipoteichoic acid is required for adhesion and virulence of
      Listeria monocytogenes.
AB  - The dlt operon of Gram-positive bacteria comprises four genes (dltA, dltB, dltC
      and dltD) that catalyse the incorporation of D-alanine residues into the cell
      wall-associated lipoteichoic acids (LTAs). In this work, we characterized the dlt
      operon of Listeria monocytogenes and constructed a D-Ala-deficient LTA mutant by
      inactivating the first gene (dltA) of this operon. The DltA- mutant did not show
      any morphological alterations and its growth rate was similar to that of the wild
      type strain. However, it exhibited an increased susceptibility to the cationic
      peptides colistin, nisin and polymyxin B. The virulence of the DltA- mutant was
      severely impaired in a mouse infection model (4 log increase in the LD50) and, in
      vitro, the adherence of the mutant to various cell lines (murine bone marrow
      derived macrophages and hepatocytes and a human epithelial cell line) was
      strongly restricted, although the amounts of surface proteins implicated in
      virulence (ActA, InlA and InlB) remains unaffected. We suggest that the decreased
      adherence of the DltA- mutant to non-phagocytic and phagocytic cells might be as
      a result of the increased electronegativity of its charge surface and/or the
      presence at the bacterial surface of adhesins possessing altered binding
      activities. These results show that the D-alanylation of the LTAs contributes to
      the virulence of the intracellular pathogen L. monocytogenes.

PMID- 11849533
TI  - Rok (YkuW) regulates genetic competence in Bacillus subtilis by directly
      repressing comK.
AB  - The Rok (YkuW) protein acts as a negative regulator of comK, which encodes the
      competence transcription factor of Bacillus subtilis. In the absence of Rok, ComK
      is overproduced, and when excess Rok is present comK transcription is inhibited.
      Rok acts transcriptionally to repress comK expression but does not affect ComK
      stability, which is controlled by the MecA switch. Gel-shift assays show that Rok
      binds directly to a DNA fragment that contains the comK promoter. SinR and AbrB
      act negatively on rok transcription, and the inactivation of rok bypasses the
      positive requirements for sinR and abrB for the expression of comK. Therefore,
      the dependence of comK expression on SinR and AbrB may be a result of their
      repression of rok transcription. It has also been shown in vivo that Rok and ComK
      can indivi-dually repress rok transcription, and that Rok and ComK bind to the
      rok promoter in vitro. These interactions establish feedback loops, and the roles
      of these circuits are discussed.

PMID- 11849534
TI  - An investigation into the compartmentalization of the sporulation transcription
      factor sigmaE in Bacillus subtilis.
AB  - Sporulation in Bacillus subtilis involves the formation of a polar septum, which
      divides the sporangium into a mother cell and a forespore. The sigmaE factor,
      which is encoded within the spoIIG operon, is a cell-specific regulatory protein
      that directs gene transcription in the mother cell. SigmaE is synthesized as an
      inactive proprotein pro-sigmaE, which is converted to the mature factor by the
      putative processing enzyme SpoIIGA. Processing of pro-sigmaE does not commence
      until after asymmetric division when sigmaE is largely confined to the mother
      cell. Processing depends on the signalling protein SpoIIR, which delays
      proteolysis until after polar septation, but the mechanism by which sigmaE is
      confined to the mother cell is not understood. Previous work favoured a model in
      which pro-sigmaE localizes to the mother cell face of the polar septum, such that
      sigmaE would be selectively released into mother cell cytoplasm. Based on the use
      of green fluorescent protein (GFP) fusions, we now report that pro-sigmaE is
      distributed approximately uniformly along all membrane surfaces and is not
      confined to the mother- cell face of the septum. Rather, our results are
      consistent with a model in which preferential and persistent transcription of the
      spoIIG operon in the mother cell and degradation of sigmaE in the forespore
      contribute to the selective accumulation of sigmaE in the mother cell. Persistent
      transcription of spoIIG after polar septation also contributes to the proper
      timing of pro-sigmaE processing.

PMID- 11849535
TI  - The parAB gene products of Pseudomonas putida exhibit partition activity in both
      P. putida and Escherichia coli.
AB  - The bacteria for which there is evidence that proteins of the ParAB family act in
      chromosome segregation also undergo developmental transitions that involve the
      ParAB homologues, raising the question of whether the partition activity is
      equivalent to that of plasmid partition systems. We have investigated the role in
      partition of the parAB locus of a free-living bacterium, Pseudomonas putida, not
      known to pass through developmental phases. A parAB deletion mutant, compared
      with wild type, showed slightly higher frequencies of anucleate cells in
      exponentially growing cultures but much higher frequencies in deceleration phase.
      This increase was growth medium dependent. Oversupply of ParA and ParB proteins
      also raised anucleate cell levels, specifically in the deceleration phase, in
      wild-type and mutant strains and regardless of medium, as well as generating
      abnormal cell morphologies. Absence or oversupply of ParAB function had either
      slight or considerable effects on growth rate, depending on temperature and
      medium. The need for the Par proteins in chromosome partition thus appears to be
      subject to the cell's physiological state. Three sequences similar to cis-acting
      stabilization sites of Bacillus subtilis are present in the P. putida oriC-parAB
      region. One was inserted into an unstable mini-F and shown to stabilize it in E.
      coli in a ParAB-dependent manner.

PMID- 11849536
TI  - Molecular characterization of type III secretion signals via analysis of
      synthetic N-terminal amino acid sequences.
AB  - Yersinia species utilize a type III secretion system to inject toxins, called
      Yops (Yersinia outer proteins), into eukaryotic cells. The N-termini of the Yops
      serve as type III secretion signals, but they do not share a consensus sequence.
      To simplify the analysis of type III secretion signals, we replaced amino acids 2
      8 of the secreted protein YopE with all permutations (27 or 128) of synthetic
      serine/isoleucine sequences. The results demonstrate that amphipathic N-terminal
      sequences, containing four or five serine residues, have a much greater
      probability than hydrophobic or hydrophilic sequences to target YopE for
      secretion. Multiple linear regression analysis of the synthetic sequences was
      used to obtain a model for N-terminal secretion signals. The model accurately
      classifies the N-terminal sequences of native type III substrates as efficient
      secretion signals.

PMID- 11849537
TI  - Functional analysis of the enteropathogenic Escherichia coli type III secretion
      system chaperone CesT identifies domains that mediate substrate interactions.
AB  - In many Gram-negative bacteria, a key indicator of pathogenic potential is the
      possession of a specialized type III secretion system, which is utilized to
      deliver virulence effector proteins directly into the host cell cytosol. Many of
      the proteins secreted from such systems require small cytosolic chaperones to
      maintain the secreted substrates in a secretion-competent state. One such
      protein, CesT, serves a chaperone function for the enteropathogenic Escherichia
      coli (EPEC) translocated intimin receptor (Tir) protein, which confers upon EPEC
      the ability to alter host cell morphology following intimate bacterial
      attachment. Using a combination of complementary biochemical approaches,
      functional domains of CesT that mediate intermolecular interactions, involved in
      both chaperone-chaperone and chaperone-substrate associations, were determined.
      The CesT N-terminal is implicated in chaperone dimerization, whereas the
      amphipathic alpha-helical region of the C-terminal, is intimately involved in
      substrate binding. By functional complementation of chaperone domains using the
      Salmonella SicA chaperone to generate chaperone chimeras, we show that CesT-Tir
      interaction proceeds by a mechanism potentially common to other type III
      secretion system chaperones.

PMID- 11849538
TI  - A maize-specifically expressed gene cluster in Ustilago maydis.
AB  - The corn pathogen Ustilago maydis requires its host plant maize for development
      and completion of its sexual cycle. We have identified the fungal mig2-1 gene as
      being specifically expressed during this biotrophic stage. Intriguingly, mig2-1
      is part of a gene cluster comprising five highly homologous and similarly
      regulated genes designated mig2-1 to mig2-5. Deletion analysis of the mig2-1
      promoter provides evidence for negative and positive regulation. The predicted
      polypeptides of all five genes lack significant homologies to known genes but
      have characteristic N-terminal secretion sequences. The secretion signals of mig2
      1 and mig2-5 were shown to be functional, and secretion of a full length Mig2-1
      eGFP fusion protein to the extracellular space was demonstrated. The central
      domains of the Mig2 proteins are highly variable whereas the C-termini are
      strongly conserved and share a characteristic pattern of eight cysteine residues.
      The mig2 gene cluster was conserved in a wide collection of U. maydis strains.
      Interestingly, some U. maydis isolates from South America had lost the mig2-4
      gene as a result of a homologous recombination event. Furthermore, the related
      Ustilago scitaminea strain, which is pathogenic on sugar cane, appears to lack
      the mig2 cluster. We describe a model of how the mig2 cluster might have evolved
      and discuss its possible role in governing host interaction.

PMID- 11849539
TI  - A potential role for periplasmic superoxide dismutase in blocking the penetration
      of external superoxide into the cytosol of Gram-negative bacteria.
AB  - Superoxide is a key component of the antibacterial weaponry of phagocytes.
      Presumably, for this reason, strains of Salmonella typhimurium express a
      periplasmic superoxide dismutase (SOD) that is essential for full virulence.
      Because most anions cannot easily penetrate lipid membranes, it is thought that
      the phagosomal superoxide either damages an unknown target on the bacterial
      surface or reacts with nitric oxide to form peroxynitrite (HOONO), a toxic
      oxidant that can freely enter bacteria. However, in this study, we tested whether
      superoxide itself could penetrate membranes. Superoxide that was generated at
      high pH (>7.5) very slowly reduced cytochrome c that was encapsulated inside
      lipid vesicles. It did so much more quickly at lower pH (<7). Under the latter
      conditions, more superoxide was protonated and uncharged (HO2*), and the
      penetrance of superoxide was proportional to the concentration of this species.
      The permeability coefficient of HO2* was determined to be 9 x 10(-4) cm sec(-1),
      just slightly lower than that of water and far higher than the value of the
      anionic form (O2-, <10(-7) cm sec(-1). When Escherichia coli mutants that lack
      periplasmic SOD were exposed to super-oxide at pH 6.5, cytosolic fumarase B was
      damaged. Damage was minimal at higher pH or in strains that contained periplasmic
      SOD. Thus, in the acidic phagolysosome, superoxide may be able to penetrate and
      attack cytosolic targets of captive bacteria. This process may contribute to the
      potency of the oxidative burst. One role of periplasmic SOD may be to avert this
      damage. In contrast, periplasmic SOD was ineffective at lowering the
      extracellular super-oxide concentration and, therefore, may have little impact
      upon HOONO formation.

PMID- 11849540
TI  - The universal stress protein paralogues of Escherichia coli are co-ordinately
      regulated and co-operate in the defence against DNA damage.
AB  - We have cloned, characterized and inactivated genes encoding putative UspA
      paralogues in Escherichia coli. The yecG (uspC), yiiT (uspD) and ydaA (uspE)
      genes were demonstrated to encode protein pro-ducts and these were mapped to
      spots in the E. coli proteomic database. Expression analysis using chromosomal
      transcriptional lacZ fusions and two-dimensional gels revealed that all usp genes
      analysed are regulated in a similar fashion. Thus, uspC, D and E are all induced
      in stationary phase and by a variety of stresses causing growth arrest of cells.
      Induction is independent of rpoS but is abolished in a deltarelA deltaspoT
      (ppGpp0) background and rescued by suppressor mutations rendering the beta
      subunit of RNA polymerase to behave like a stringent polymerase. Ectopic
      elevation of ppGpp levels in growing cells, by overproducing the RelA protein,
      triggered the induction of all usp genes. The expression of all usp genes was
      also elevated by a mutation in the ftsK cell division gene, and this super
      induction could be suppressed by inactivating recA indicating that the usp
      paralogues are involved in the management of DNA. Indeed, uspC, uspD and uspE
      deletion mutants were all found to be sensitive to UV exposure. Overexpression of
      UspD could compensate for the lack of a chromosomal uspD gene but not a uspA
      gene. Similarly, UspA overproduction could only compensate for the lack of
      chromosomal uspA. Moreover, combination of usp mutations had no additive effect
      on UV sensitivity indicating that they are all co-operating and required in the
      same pathway, which could explain the co-ordinated regulation of the genes.

PMID- 11849542
TI  - Plasmid transfer from Streptomyces to Mycobacterium smegmatis by spontaneous
      transformation.
AB  - Hybrids of the Streptomyces coelicolor conjugative plasmid SCP2* and the
      Mycobacterium plasmid pAL5000 were transferred from Streptomyces coelicolor or
      Streptomyces lividans to Mycobacterium smegmatis mc2155 in plate crosses.
      Inactivation of the SCP2* transfer function did not prevent or reduce plasmid
      transfer. This transfer was DNase I sensitive and thus involved release of DNA
      from Streptomyces, followed by transformation of M. smegmatis. M. smegmatis
      growing on specific solid media was also transformed by pure CCC and linear
      plasmid DNA. Small plasmids were taken up intact but large plasmids suffered
      deletions. Competence developed within 24 h of incubation at 30 degrees C or 37
      degrees C, and up to 400 transformants were obtained per microg of CCC plasmid
      DNA. Transformation frequencies were higher when M. smegmatis was co-cultivated
      with plasmid-free Streptomyces, but unaffected by resident homologous sequences
      or inactivation of recA in M. smegmatis. Spontaneous transformation was also
      observed with a circular Streptomyces transposable element which inserted into
      chromosomal sites. Transformative plasmid transfer was also shown to occur
      between M. smegmatis strains. This is the first report of non-artificially
      induced, spontaneous plasmid transformation in Mycobacterium.

PMID- 11849541
TI  - Regulation of gene expression in Vibrio cholerae by ToxT involves both
      antirepression and RNA polymerase stimulation.
AB  - Co-ordinate expression of many virulence genes in the human pathogen Vibrio
      cholerae is under the direct control of the ToxT protein, including genes whose
      products are required for the biogenesis of the toxin-co-regulated pilus (TCP)
      and cholera toxin (CTX). This work examined interactions between ToxT and the
      promoters of ctx and tcpA genes. We found that a minimum of three direct repeats
      of the sequence TTTTGAT is required for ToxT-dependent activation of the ctx
      promoter, and that the region from -85 to -41 of the tcpA promoter contains
      elements that are responsive to ToxT-dependent activation. The role of H-NS in
      transcription of ctx and tcpA was also analysed. The level of activation of ctx
      lacZ in an E. coli hns- strain was greatly increased even in the absence of ToxT,
      and was further enhanced in the presence of ToxT. In contrast, H-NS plays a
      lesser role in the regulation of the tcpA promoter. Electrophoretic mobility
      shift assays demonstrated that 6x His-tagged ToxT directly, and specifically,
      interacts with both the ctx and tcpA promoters. DNase I footprinting analysis
      suggests that there may be two ToxT binding sites with different affinity in the
      ctx promoter and that ToxT binds to -84 to -41 of the tcpA promoter. In vitro
      transcription experiments demonstrated that ToxT alone is able to activate
      transcription from both promoters. We hypothesize that under conditions
      appropriate for ToxT-dependent gene expression, ToxT binds to AT-rich promoters
      that may have a specific secondary conformation, displaces H-NS and stimulates
      RNA polymerase resulting in transcription activation.

PMID- 11849543
TI  - The Fap1 fimbrial adhesin is a glycoprotein: antibodies specific for the glycan
      moiety block the adhesion of Streptococcus parasanguis in an in vitro tooth
      model.
AB  - Streptococcus parasanguis is a primary colonizer of the tooth surface and plays a
      pivotal role in the formation of dental plaque. The fimbriae of S. parasanguis
      are important in mediating adhesion to saliva-coated hydroxylapatite (SHA), an in
      vitro tooth adhesion model. The Fap1 adhesin has been identified as the major
      fimbrial subunit, and recent studies suggest that Fap1 is a glycoprotein.
      Monosaccharide analysis of Fap1 purified from the culture supernatant of S.
      parasanguis indicated the presence of rhamnose, glucose, galactose, N
      acetylglucosamine and N-acetylgalactosamine. A glycopeptide moiety was isolated
      from a pronase digest of Fap1 and purified by immunoaffinity chromatography. The
      monosaccharide composition of the purified glycopeptide was similar to that of
      the intact molecule. The functionality of the glycan moiety was determined using
      monoclonal antibodies (MAbs) specific for the intact Fap1 glycoprotein. These
      antibodies were grouped into two categories based on their ability to block
      adhesion of S. parasanguis to SHA and their corresponding specificity for either
      protein or glycan epitopes of the Fap1 protein. 'Non-blocking' MAb epitopes were
      mapped to unique protein sequences in the N-terminus of the Fap1 protein using
      non-glycosylated recombinant Fap1 proteins (rFap1 and drFap1) expressed in
      Escherichia coli. In contrast, the 'blocking' antibodies did not bind to the
      recombinant Fap1 proteins, and were effectively competed by the binding to the
      purified glycopeptide. These data suggest that the 'blocking' antibodies are
      specific for the glycan moiety and that the adhesion of S. parasanguis is
      mediated by sugar residues associated with Fap1.

PMID- 11849544
TI  - RNase E levels in Escherichia coli are controlled by a complex regulatory system
      that involves transcription of the rne gene from three promoters.
AB  - The rne gene of Escherichia coli encodes RNase E, an essential endoribonuclease
      that is involved in both mRNA decay and rRNA processing. Here we present evidence
      that the gene is transcribed from three promoters: p1, p2 and p3. The p2 and p3
      promoters map 34 and 145 nt upstream from the previously characterized rne
      promoter, p1, generating unusually long 5' UTRs of 395 and 506 nt respectively.
      Based on promoter-lacZ transcriptional fusions, p1 is a more efficient promoter
      than either p2 or p3. Low copy number or single copy number vectors carrying rne
      transcribed from either p1, p2 or p3 alone complement the rne 1018::bla deletion
      mutation at 30 degrees C, 37 degrees C and 44 degrees C. However, normal
      autoregulation requires the presence of all three promoters. A comparison among
      intracellular levels of RNase E, the half-lives of the rpsO, rpsT and rne mRNAs,
      and growth rates, indicates that the cell contains a considerable excess of RNase
      E protein. In addition, when the rne transcript is stabilized at low RNase E
      levels, it is not efficiently translated.

PMID- 11849545
TI  - Cryptic plasmids of Mycobacterium avium: Tn552 to the rescue.
AB  - Plasmids have been described in almost all bacterial species analysed and have
      proven to be essential genetic tools. In many bacteria these extrachromosomal
      DNAs are cryptic with no known markers or function, which makes their
      characterization and genetic exploitation extremely difficult. Here we describe a
      system that will allow the rescue of any circular DNA (plasmid or phage) using an
      in vitro transposition system to deliver both a selectable marker (kanamycin) and
      an Escherichia coli plasmid origin of replication. In this study, we demonstrate
      the rescue of four cryptic plasmids from the opportunistic pathogen Mycobacterium
      avium. To evaluate the host range of the rescued plasmids, we have examined their
      ability to be propagated in Mycobacterium smegmatis and Mycobacterium bovis BCG,
      and their compatibility with other mycobacterial plasmids. In addition, we use a
      library of transposon insertions to sequence one plasmid, pVT2, and to begin a
      genetic analysis of plasmid genes. Using this approach, we identified a putative
      conjugative relaxase, suggesting this myco-bacterial plasmid is transferable, and
      three genes required for plasmid establishment and replication.

PMID- 11849546
TI  - Co-operative binding of triplicate carbohydrate-binding modules from a
      thermophilic xylanase.
AB  - Family 6 carbohydrate-binding modules were amplified by polymerase chain reaction
      (PCR) from Clostridium stercorarium strain NCIB11754 genomic DNA as a triplet.
      Individually, these modules bound to xylooligosaccharides and
      cellooligosaccharides with affinities varying from approximately 3 x 10(3) M(-1)
      to approximately 1 x 10(5) M(-1). Tandem and triplet combinations of these
      modules bound co-operatively to soluble xylan and insoluble cellulose to give
      approximately 20- to approximately 40-fold increases in affinity relative to the
      individual modules. This co-operativity was an avidity effect resulting from the
      modules within the tandems and triplet interacting simultaneously with proximal
      binding sites on the polysaccharides. This occurred by both intrachain and
      interchain interactions. The duplication or triplication of modules appears to be
      linked to the growth temperature of the organism; co-operativity in these
      multiplets may compensate for the loss of affinity at higher temperatures.

PMID- 11849547
TI  - Mutational analysis of F-pilin reveals domains for pilus assembly, phage
      infection and DNA transfer.
AB  - The F-pilus has been implicated in recipient cell recognition during the
      establishment of a stable mating pair before conjugation as well as forming part
      of the conjugative pore for DNA transfer. The F-pilus is the site of attachment
      of the filamentous phages (M13, f1 and fd), which attach to the F-pilus tip, and
      the RNA phages, R17 and Qbeta, which attach to different sites exposed on the
      sides of the pilus. R17 has been shown to undergo eclipse, or capsid release,
      outside the cell on pili attached to cells. New and existing mutants of traA
      combined with natural variants of F-pilin were assayed for pilin stability and
      processing, pilus elongation, transfer, phage sensitivity and R17 eclipse.
      Phenotypes of these mutants indicated that the F-pilin subunit contains specific
      regions that can be associated with pilus assembly, phage sensitivity and DNA
      transport. Mutations involving lysines and phenylalanines within residues 45-60
      suggest that these residues might participate in transmitting a signal down the
      length of the pilus that initiates DNA transfer or R17 eclipse.

PMID- 11849548
TI  - Activation of Shiga toxin type 2d (Stx2d) by elastase involves cleavage of the C
      terminal two amino acids of the A2 peptide in the context of the appropriate B
      pentamer.
AB  - Shiga toxins (Stx) are potent ribosome-inactivating toxins that are produced by
      Shigella dysenteriae type 1 or certain strains of Escherichia coli. These toxins
      are composed of one A subunit that can be nicked and reduced to an enzymatically
      active A1(approximately 27 kDa) and an A2 peptide (approximately 4 kDa) as well
      as a pentamer of B subunits (approximately 7 kDa/monomer) that binds the
      eukaryotic cell. Purified Shiga toxin type 2d is activated 10- to 1000-fold for
      Vero cell toxicity by preincubation with mouse or human intestinal mucus or
      purified mouse elastase, whereas Stx2, Stx2c, Stx2e and Stx1 are not activatable.
      E. coli strains that produce the activatable Stx2d are more virulent in a
      streptomycin (str)-treated mouse model of infection [lethal dose 50% (LD50) =
      101] than are E. coli strains that produce any other type of Stx (LD50 = 1010).
      To identify the element(s) of Stx2d that are required for mucus-mediated
      activation, toxin genes were constructed such that the expressed mutant toxins
      consisted of hybrids of Stx2d and Stx1, Stx2 or Stx2e, contained deletions of up
      to six amino acids from the C-terminus of the A2 of Stx2d or were altered in one
      or both of the two amino acids of the A2 of Stx2d that represent the only amino
      acid differences between the activatable Stx2d and the non-activatable Stx2c.
      Analysis of these mutant toxins revealed that the A2 portion of Stx2d is required
      for toxin activation and that activation is abrogated if the Stx1 or Stx2e B
      subunit is substituted for the Stx2d B polypeptide. Furthermore, mass
      spectrometry performed on buffer- or elastase-treated Stx2d indicated that the A2
      peptide of the activated Stx2d was two amino acids smaller than the A2 peptide
      from buffer-treated Stx2d. This finding, together with the toxin hybrid results,
      suggests that activation involves B pentamer-dependent cleavage by elastase of
      the C-terminal two amino acids from the Stx2d A2 peptide.

PMID- 11849549
TI  - Post-transcriptional enhancement of Escherichia coli bgl operon silencing by
      limitation of BglG-mediated antitermination at low transcription rates.
AB  - The silent bgl operon of Escherichia coli is activated by spontaneous mutations
      that derepress its promoter. In addition, expression depends on specific
      transcriptional antitermination within the operon by the antiterminator protein
      BglG. Here, we show that BglG-mediated antitermination limits expression of the
      bgl operon when the cellular transcription rate is low. The expression levels of
      chromosomally encoded activated bgl operon alleles are low but increase
      significantly when BglG protein is provided in trans or when the expression is
      rendered independent of BglG-mediated antitermination by mutation of the
      terminator. Plasmid-encoded activated bgl operon alleles are expressed at high
      levels. Moreover, a moderate (threefold) further increase in the transcription
      rate of chromosomally encoded activated bgl operon alleles in an rpoS mutant can
      result in high (up to 50-fold increased) expression levels. These data show that
      the expression of the bgl operon does not correlate linearly with its cellular
      transcription rate. Moderate differences in the transcription initiation rate are
      amplified post-transcriptionally into large changes in the expression level of
      the operon by the requirement of a threshold for BglG-mediated antitermination.
      Implications for bgl operon regulation by global regulators H-NS, RpoS and others
      are discussed.

PMID- 11849550
TI  - Role of the ribosomal stalk components in the resistance of Aspergillus fumigatus
      to the sordarin antifungals.
AB  - Aspergillus fumigatus, an important human nosocomial pathogen, is resistant to
      sordarin derivatives, a new family of antifungals that inhibit protein synthesis
      by interaction with the EF-2-ribosomal stalk complex. To explore the role of the
      A. fumigatus ribosome in the resistance mechanism, the fungal stalk proteins were
      biochemically and genetically characterized and expressed in the sensitive
      Saccharomyces cerevisiae. Two acidic phosphoproteins homologous to the 12 kDa P1
      and P2 proteins described in other organisms were found together with the 34 kDa
      P0 protein, the third stalk component. The genes encoding each fungal stalk
      protein were expressed in mutant S. cerevisiae strains lacking the equivalent
      proteins. Both AfP1 and AfP2 proteins interact with their yeast counterparts of
      the opposite type and bind to the ribosomal particles in the presence of either
      the S. cerevisiae or the A. fumigatus P0 protein. The A. fumigatus acidic
      phosphoproteins did not alter the yeast ribosome sordarin sensitivity. On the
      contrary, the presence of the fungal P0 induces in vivo and in vitro resistance
      to sordarin derivatives when present in the yeast ribosome. The mutations A117-
      >E, P122-->R and G124-->V in A. fumigatus P0 reduce the resistance capacity of
      the protein. An S. cerevisiae strain with the complete ribosomal stalk of A.
      fumigatus was obtained, which could be useful for the screening of new
      antifungals against this pathogenic fungus.

PMID- 11849551
TI  - Leaderless mRNAs in bacteria: surprises in ribosomal recruitment and
      translational control.
AB  - It is commonly believed that the translational efficiency of prokaryotic mRNAs is
      intrinsically determined by both primary and secondary structures of their
      translational initiation regions. However, for leaderless mRNAs starting with the
      AUG initiating codon occurring in bacteria, archaea and eukaryotes, there is no
      evidence for ribosomal recruitment signals downstream of the 5'-terminal AUG that
      seems to be the only necessary and constant element. Studies in Escherichia coli
      have brought to light that the ratio of initiation factors IF2 and IF3 plays a
      decisive role in translation initiation of leaderless mRNA, indicating that the
      translational efficiency of this mRNA class can be modulated depending on the
      availability of components of the translational machinery. Recent data suggested
      that the start codon of bacterial leaderless mRNAs is recognized by a ribosome
      IF2-fMet-tRNA complex, an intermediate equivalent to that obligatorily formed
      during translation initiation in eukaryotes, which points to a conceptual
      similarity in all initiation pathways. In fact, the faithful translation of
      leaderless mRNAs in heterologous systems shows that the ability to translate
      leaderless mRNAs is an evolutionarily conserved function of the translational
      apparatus.

PMID- 11849552
TI  - A two-component signal transduction system involved in nickel sensing in the
      cyanobacterium Synechocystis sp. PCC 6803.
AB  - In the cyanobacterium Synechocystis sp. PCC 6803, genes for Ni2+, Co2+, and Zn2+
      resistance are grouped in a 12 kb gene cluster. The nrsBACD operon is composed of
      four genes, which encode proteins involved in Ni2+ resistance. Upstream from
      nrsBACD, and in opposite orientation, a transcription unit formed by the two
      genes rppA and rppB has been reported previously to encode a two-component signal
      transduction system involved in redox sensing. In this report, we demonstrate
      that rppA and rppB (here redesigned nrsR and nrsS respectively) control the Ni2+
      dependent induction of the nrsBACD operon and are involved in Ni2+ sensing. Thus,
      expression of the nrsBACD operon was not induced by Ni2+ in a nrsRS mutant
      strain. Furthermore, nrsRS mutant cells showed reduced tolerance to Ni2+. Whereas
      the nrsBACD operon is transcribed from two different promoters, one constitutive
      and the other dependent on the presence of Ni2+ in the medium, the nrsRS operon
      is transcribed from a single Ni2+-inducible promoter. The nrsRS promoter is
      silent in a nrsRS mutant background suggesting that the system is autoregulated.
      Purified full length NrsR protein is unable to bind to the nrsBACD-nrsRS
      intergenic region; however, an amino-terminal truncated protein that contains the
      DNA binding domain of NrsR binds specifically to this region. Our nrsRS mutant,
      which carries a deletion of most of the nrsR gene and part of the nrsS gene, does
      not show redox imbalance or photosynthetic gene mis-expression, contrasting with
      the previously reported nrsR mutant.

PMID- 11849553
TI  - Clostridial VirR/VirS regulon involves a regulatory RNA molecule for expression
      of toxins.
AB  - We analysed the region encoding VR-RNA (VirR-regulated RNA), which has been
      reported to be positively regulated by the two-component VirR/VirS system in
      Clostridium perfringens. The VR-RNA promoter identified by primer extension
      analysis was preceded by a probable VirR-binding site (CCAGTTNNNCAC), which
      resembled a repeated sequence motif present in the promoter region of the theta
      toxin (pfoA) gene. A VR-RNA-null mutant, constructed by a homologous
      recombination, exhibited a reduced amount of transcription of the alpha- (plc)
      and kappa-toxin (colA) genes, which was restored by the complementation of intact
      VR-RNA, indicating that the VR-RNA region plays an important role in the
      regulation of the plc and colA genes in C. perfringens. It was found that the
      regulatory effect was observed even when the hyp7 gene encoded on VR-RNA was
      deleted or a nonsense mutation was introduced in the hyp7-coding region. We found
      that the small 3'-portion of VR-RNA was sufficient for the activation of toxin
      genes, which suggested that VR-RNA itself could act as an RNA regulatory molecule
      for the plc and colA genes mediating the regulatory information from the
      VirR/VirS system in C. perfringens.

PMID- 11849558
TI  - What is the basis of transmissible spongiform encephalopathy induced
      neurodegeneration and can it be repaired?
AB  - Once an animal becomes infected with a prion disease, or transmissible spongiform
      encephalopathy (TSE), the progression of infection is relentless and inevitably
      fatal, although often with such prolonged incubation periods that an alternative
      cause of death can intervene. Infection has been compared to 'setting a clock'
      which then runs inexorably as the disease spreads, usually through the
      lymphoreticular system and then via peripheral nerves to the central nervous
      system (CNS), although the mechanism controlling the protracted progression is
      not known. Clinical disease develops as characteristic degenerative changes in
      the CNS progress, but the molecular basis for this pathology is not clear,
      particularly the relationship between the deposition of abnormal PrP and neuronal
      dysfunction. Recent research has identified several means of slowing (if not
      stopping) the clock when infection has not yet reached the CNS; although the
      potential for later stage therapies seems limited, neuroprotective strategies
      which have been shown to be effective in other neurodegenerative conditions may
      also ameliorate TSE induced CNS pathology. This review focuses on our current
      knowledge of the key events following infection of the CNS and the opportunities
      for intervention once the CNS has become infected.

PMID- 11849559
TI  - Progressive supranuclear palsy: neuronal and glial cytoskeletal pathology in the
      higher order processing autonomic nuclei of the lower brainstem.
AB  - The medial and lateral parabrachial nuclei (MPB, LPB), the gigantocellular
      reticular nucleus (GI), the raphes magnus (RMG) and raphes obscurus nuclei (ROB),
      as well as the intermediate reticular zone (IRZ) represent pivotal subordinate
      brainstem centres, all of which control autonomic functions. In this study, we
      investigated the occurrence and severity of the neuronal and glial cytoskeletal
      pathology in these six brainstem nuclei from 17 individuals with clinically
      diagnosed and neuropathologically confirmed progressive supranuclear palsy (PSP).
      The association between the severity of the pathology and the duration of the
      disease was investigated by means of correlation analysis. The brainstem nuclei
      in all of the PSP cases were affected by the neuronal cytoskeletal pathology,
      with the IRZ and GI regularly showing severe involvement, the MPB, RMG, and ROB
      marked involvement, and the LPB mild involvement. In the six nuclear greys
      studied, glial cells undergo alterations of their cytoskeleton on an irregular
      basis, whereby diseased oligodendrocytes predominantly presented as coiled bodies
      and affected astrocytes as thorn-shaped astrocytes. In all six nuclei, the
      severity of the neuronal or glial cytoskeletal pathology showed no correlation
      with the duration of PSP. In view of their functional role, the neuronal
      pathology in the nuclei studied offers a possible explanation for the autonomic
      dysfunctions that eventually develop in the course of PSP.

PMID- 11849560
TI  - Lysosomal storage results in impaired survival but normal neurite outgrowth in
      dorsal root ganglion neurones from a mouse model of Sandhoff disease.
AB  - Sandhoff disease is a heritable lysosomal storage disease resulting from impaired
      degradation of GM2 ganglioside and related substrates. A mouse model of Sandhoff
      disease created by gene targeting displays progressive neurological
      manifestations, similar to patients with the disease. In the present in vivo and
      in vitro studies, we examined morphological and functional abnormalities of
      dorsal root ganglion (DRG) neurones in Sandhoff disease mice at an asymptomatic
      stage (approximately 1 month of age). Light microscopic studies with Nissl
      staining and immunocytochemistry suggested extensive intracytoplasmic storage of
      GM2 ganglioside in the Sandhoff mouse DRG neurones. These findings were
      consistent with the results of electron microscopy, in which a huge number of
      pleomorphic inclusion bodies immunoreactive for GM2 ganglioside were present in
      the cytoplasm of the neurones. The inclusion bodies were also identified in
      satellite cells and Schwann cells in the Sandhoff mouse DRG. The survival ratios
      of DRG neurones after 1, 2, 4 and 6 days in culture were significantly lower in
      the Sandhoff mice than in the age-matched heterozygous mice. The ratio of neurite
      bearing cells on poly-l-lysine-coated dishes after 2 days in culture was also
      lower by approximately 10% in the Sandhoff mice compared to the heterozygotes,
      but additional coating of laminin onto poly-l-lysine dramatically enhanced the
      neurite extension from the neurones in both groups of mice. These results
      indicate that accumulation of GM2 ganglioside in DRG neurones impairs the
      capability of the neurones to survive in vitro, although viable neurones from the
      Sandhoff mice in culture can regenerate neurites nearly as well as unaffected
      neurones.

PMID- 11849561
TI  - Abnormal ubiquitination of axons in normally myelinated white matter in multiple
      sclerosis brain.
AB  - The hallmark of the lesions in multiple sclerosis (MS) is inflammatory
      demyelination with sparing of axons. Recent neuropathological and
      neuroradiological investigations show that structural changes of the axons occur,
      both in plaques and in the normal appearing white matter. A better understanding
      of the axonal damage in MS is important, since this may be responsible for
      permanent disability. We have investigated the immunoreactivity for ubiquitin, a
      sensitive method to detect axonal dystrophy and accumulation of abnormal proteins
      in pathological conditions of the nervous system, in the brains of six cases of
      MS (age range 39-66 years). Tissue blocks were fixed in formalin and embedded in
      paraffin. A panel of antibodies was used: anti-ubiquitin, anti-neurofilament (SMI
      31 + SMI-32), anti-amyloid precursor protein and anti-PGP9.5. We focused our
      attention on chronic plaques, recognized by the absence of Luxol Fast Blue B
      positive inclusions in macrophages. SMI-31 + SMI-32 showed the presence of a
      variable amount of axons within the plaques; the axonal network within the
      plaques was looser than outside. No ubiquitin reactivity was present in chronic
      plaques. In the normally myelinated white matter surrounding the plaques, a dense
      granular ubiquitin immunoreactivity was found both near and far from the plaque
      edge. No similar staining was found in control brains. Ubiquitination is the
      first step of a non-lysosomal degradation pathway of proteins. The present
      findings suggest a derangement of this proteolytic pathway in the axons outside
      the plaques, possibly as a consequence of chronic absence of myelin in the axonal
      segment inside the plaque. The spectrum of axonal changes in MS appears to be
      wider than expected and involves the apparently normal white matter.

PMID- 11849562
TI  - Fibrous meningeal tumours with extensive non-calcifying collagenous whorls and
      glial fibrillary acidic protein expression: the whorling-sclerosing variant of
      meningioma.
AB  - Meningiomas comprise a wide range of morphological patterns. We describe unusual
      fibrous meningeal tumours in two patients, composed of extensive non-calcifying
      collagenous whorls of varying size, resembling non-calcified psammoma bodies,
      while interposed tumour cells are sparse. Immunohistochemistry showed expression
      of S-100, vimentin and glial fibrillary acidic protein, whereas only single
      tumour cells stained for epithelial membrane antigen. Electron microscopy
      detected desmosomes or desmosome-like structures in both specimens. We conclude
      that these tumours represent a peculiar whorling-sclerosing variant of fibrous
      meningioma. Recognition of this meningioma variant is important in the
      differential diagnosis of meningioma versus other fibrous tumours of the
      meninges, including solitary fibrous tumours of the meninges, unusual forms of
      desmoplastic gliomas or chondroid tumours.

PMID- 11849563
TI  - Childhood meningiomas associated with meningioangiomatosis: report of five cases
      and literature review.
AB  - Meningioangiomatosis is a unique, rare hamartomatous lesion. Meningiomas arising
      in the background of meningioangiomatosis are rare conditions which
      pathologically and radiologically mimic invasive meningiomas, but have a benign
      clinical course in children and young adults. In this study, five such cases are
      reported. To our knowledge, this is the largest reported collection of
      meningiomas associated with meningioangiomatosis. Less immunoreactivity for
      progesterone receptor and high Ki-67 labelling index are generally known to be
      associated with invasive meningiomas. However, high expression of progesterone
      receptor and low Ki-67 labelling index in the present cases supports the idea
      that brain invasion is not an indicator of malignancy but an independent finding
      associated with meningiomas which have arisen from meningioangiomatosis. We
      emphasize the good prognosis of such tumours and discuss pathogenesis of
      meningiomas with meningioangiomatosis.

PMID- 11849564
TI  - Prognostic implications of microvessel morphometry in diffuse astrocytic
      neoplasms.
AB  - Astrocytic brain tumours, particularly malignant astrocytomas, are recognized to
      be highly vascular neoplasms with potent angiogenic activity. Recent research has
      shown that quantification of microvessel density (MVD), as a measure of the
      degree of angiogenesis, constitutes a strong prognostic indicator in patients
      with astrocytomas. However, the significance of other morphometric aspects of
      microvessel network has not been tested so far. In this report, histological
      sections from 70 astrocytomas (grades II to IV), immunostained for CD34, were
      evaluated by image analysis for the quantification of MVD, total vascular area
      (TVA), and microvascular branching, as well as several morphometric parameters
      related to vessel size or shape. Minor axis length increased with grade (P =
      0.045) but MVD and TVA presented a peak in grade III (P = 0.033 and P < 0.001,
      respectively). Size and shape related parameters affected survival in univariate
      analysis of grade IV and grades II/III, respectively. In multivariate analysis,
      only branching counts, along with age and grade, were the independent predictors
      of survival. Although MVD, TVA and branching counts were adversely related to
      disease-free survival in grades II and III (univariate analysis), only TVA
      remained statistically significant in multivariate analysis. It is concluded that
      TVA and branching counts are prognostically more informative than MVD for
      patients with diffuse astrocytic tumours.

PMID- 11849565
TI  - Cerebrospinal fluid outflow resistance in sheep: impact of blocking cerebrospinal
      fluid transport through the cribriform plate.
AB  - Recent studies in sheep suggest that a significant proportion of global
      cerebrospinal fluid (CSF) drainage (50% or greater) occurs through the cribriform
      plate into nasal mucosal lymphatics. If this is true, obstructing CSF clearance
      through the cribriform plate should have an impact on the ability of the
      intracranial pressure regulating systems to compensate for volume infusions. To
      test this concept, bolus infusions of artificial CSF were administered into one
      lateral ventricle in sheep and the intracranial pressure monitored from the
      contralateral side. Peak intracranial pressures (ICP) were measured and CSF
      outflow resistances were calculated from the pressure patterns observed in
      response to bolus infusions administered before and after the cribriform plate
      was sealed in the same animal. To obstruct the cribriform plate, a portion of
      nasal bone was removed to expose the nasal mucosa. The olfactory mucosa, a
      portion of the nasal mucosa and all soft tissue on the extracranial surface of
      the cribriform plate were scraped away with a curette and the bone surface sealed
      with bone wax. Obstruction of CSF transport through the cribriform plate
      increased the peak ICP after infusion (P = 0.016) and augmented the time required
      for ICP to return to baseline. CSF outflow resistance was elevated approximately
      2.7 times (P = 0.006). When the cribriform plate was left intact (sham surgery),
      no significant changes in peak ICP or CSF outflow resistance were observed. We
      conclude that the cribriform plate represents an important site for CSF
      clearance. Obstruction of this pathway reduces volumetric CSF transport
      significantly.

PMID- 11849566
TI  - Observations on the structure of myelin lacking the major proteolipid protein.

PMID- 11849569
TI  - Is cricoid pressure necessary?

PMID- 11849567
TI  - Macrophage and microglial cell immunoreactivity for PrP(c) in a random post
      mortem population.

PMID- 11849570
TI  - Pharmacological support for children with myocardial dysfunction.

PMID- 11849571
TI  - Oral midazolam with an antacid may increase the speed of onset of sedation in
      children prior to general anaesthesia.
AB  - BACKGROUND: The aim of the study was to see whether sodium citrate solution would
      speed the gastric absorption of oral midazolam. METHODS: Forty presurgical ASA I
      and II patients (aged 2-6 years) were randomly assigned to one of two groups.
      Group I received midazolam 0.5 mg x kg(-1) mixed with sodium citrate while group
      II (control) received midazolam 0.5 mg x kg(-1) mixed with Hawaiian fruit punch.
      RESULTS: There was no statistical difference between the ages, weights,
      preoperative sedation and anxiety scores in the two groups. After premedication,
      the onset of sedation (mean +/- SD) measured by the first change in sedation
      score was found to be significantly faster (P < 0.05) in group I (17.8 +/- 7.11)
      compared with group II (21.9 +/- 5.34). There was no statistical difference in
      anxiety at any time intervals, separation or induction scoring for both groups.
      Gastric volumes and the pH of gastric aspirates between the two groups were not
      statistically significant. CONCLUSIONS: The time to onset of sedation can
      potentially be shortened, by using a preparation of intravenous midazolam and
      antacid, given orally.

PMID- 11849572
TI  - The analgesic efficacy of preoperative high dose (40 mg x kg(-1)) oral
      acetaminophen after bilateral myringotomy and tube insertion in children.
AB  - BACKGROUND: The purpose of this study was to measure the plasma levels and
      analgesic effectiveness of a dose of 40 mg x kg(-1) of preoperative oral
      acetaminophen. METHODS: Thirty children aged 55 (17-72) months undergoing
      bilateral myringotomy and tube insertion (BMT) received acetaminophen 40 mg x kg(
      1) p.o. preoperatively. Plasma levels were measured, at 29 (10-51) min and at 60
      min in the postanaesthesia care unit (PACU). Children's Hospital of Eastern
      Ontario Pain Scale (CHEOPS), for all subjects and the Poker Chip Tool (PCT) a
      self-report scale for subjects aged > 4 years, were used. After discharge, 24-h
      analgesic efficacy was evaluated using an observer Visual Analogue Scale (VAS)
      score and further acetaminophen use was recorded. RESULTS: Plasma concentrations
      were 259 (60-391) micromol x l(-1) and 250 (135-450) micromol x l(-1),
      respectively. All 60 min plasma concentrations were > or = 70 micromol x l(-1)
      (ED50 for adenotonsillectomy) and less than 800 micromol x l(-1) (associated with
      toxicity). Twenty-six subjects (87%) had adequate analgesia (CHEOPS < or = 8).
      The PCT was only understood in the PACU by 13 of the 21 children > 4 years (62%).
      The median worst 24-h observer VAS was 0.5 (0-5.5) (27 subjects). No further
      analgesic was required after discharge in 16/28 (57%). A higher plasma level was
      associated with fewer doses of acetaminophen after discharge (r = -0.36, P=0.05).
      CONCLUSIONS: No relationship was evident between age, the 60 min plasma
      acetaminophen level and the CHEOPS carried out at the same time. Acetaminophen 40
      mg x g(-1) p.o. results in 60 min plasma levels of 250 (135-450) micromol x l(
      1). The in-hospital analgesic efficacy was 87% (CHEOPS < 9, no further
      analgesics) and the 24-h efficacy was 57% (need for further acetaminophen).

PMID- 11849573
TI  - A survey of practice of tracheal intubation without muscle relaxant in paediatric
      patients.
AB  - BACKGROUND: Because of the renewed interest in intubation in children without
      relaxants, over a period of 1 month, the anaesthesiologists of five paediatric
      universitary teaching hospitals were asked to complete a questionnaire each time
      they performed a tracheal intubation without muscle relaxant. METHODS: Intubating
      conditions were assessed with five items. Each item was graded on a four-point
      scale. Intubating conditions were judged acceptable when all items scored 2 or
      less. Episodes of oxygen desaturation and failed intubations were noted. Data are
      expressed as mean +/- SD (extremes). RESULTS: Five hundred and two questionnaires
      were completed during the study period. Children were aged 61 +/- 50 (1-180)
      months old. Induction of anaesthesia was performed with sevoflurane for 62.6% of
      the children (endtidal concentration 5.9 +/- 1.5%) and propofol for 28.9% (dose
      5.8 +/- 4.2 mg x kg(-1). Opioids were associated with these hypnotics in 53.2% of
      the children. Tracheal intubation was successful in 87.1% of the children.
      Sevoflurane produced better intubating conditions than propofol. Sevoflurane
      requirements for tracheal intubation may be higher in infants aged less than 6
      months old than in older children. A severe decrease in SpO2 (< or = 90%) was
      observed in 15.9% of the infants aged less than 1 year old and in 1.7% of the
      children, respectively (P < 0.0001). CONCLUSIONS: Sevoflurane is the most
      commonly used agent for tracheal intubation without relaxants with higher doses
      being required in infants aged less than 6 months. Propofol, even with opioids,
      was not so successful.

PMID- 11849574
TI  - The use of the cuffed oropharyngeal airway in paediatric patients.
AB  - BACKGROUND: The cuffed oropharyngeal airway (COPA) is a device which has already
      been demonstrated to be suitable for anaesthetized adult patients undergoing
      either spontaneous or mechanical ventilation. There are few reports on the use of
      the COPA in children. In this study, the authors assessed the COPA in paediatric
      patients undergoing minor surgery. METHODS: The same anaesthesiologist inserted
      the COPA in 40 consecutive paediatric patients, ASA I and II, aged 1.8-15.3
      years. (7.4 +/- 3.9), after induction of anaesthesia with N2O/O2/sevoflurane.
      COPA size was chosen by measuring the distal tip of the device at the angle of
      the jaw with the COPA perpendicular to the patient's bed. The proper positioning
      of the COPA was assessed by observing thoracoabdominal movements, regular
      capnograph trace, the reservoir bag movements and SpO2 > 94% with a fraction of
      inspired oxygen of 0.5. Anaesthesia was maintained with 1 MAC halothane,
      sevoflurane, or isoflurane in N2O/O2 (50%) and the patients were spontaneously
      breathing. The stability of the COPA following changes in head, neck and body
      position was tested. We recorded the duration time for COPA insertion, the side
      effects of placement of the COPA and during the intraoperative period, the number
      of attempts, the type of manipulation in order to provide an effective airway and
      postoperative symptoms, such as the presence of blood on the device, sore throat,
      neckache, jaw pain and PONV. RESULTS: Successful COPA insertion at the first
      attempt was 90% and at the second attempt in the remaining 10%. The most frequent
      airway manipulations were head tilt in 27.5% (obtained by a pillow under
      shoulders) and chin lift in 5%. No complications both at COPA placement nor
      during the intraoperative period were observed. On the basis of weight and age,
      the COPA size was no. 8 in 50%, no. 9 in 30%, no. 10 in 12.5%, and no. 11 in
      7.5%. The COPA demonstrated stability after changes in head, neck and body
      position. Postoperative complications were the presence of blood stains in one
      case and PONV in six cases (15%). CONCLUSIONS: The COPA is an extratracheal
      airway device suitable in paediatric patients undergoing general anaesthesia with
      spontaneous ventilation for minor surgery and other painful procedures. This
      study shows that for paediatric patients: (i) complications seem to be rare; (ii)
      the COPA allows hands free anaesthesia; (iii) specific indication for the COPA
      could be obese patients with a small mouth; and (iv) COPA sizing can be easily
      established by the weight or age of the patients.

PMID- 11849575
TI  - Noninvasive intraoperative monitoring of carbon dioxide in children: endtidal
      versus transcutaneous techniques.
AB  - BACKGROUND: The current study prospectively compares the accuracy of the
      intraoperative use of transcutaneous (Tc) and endtidal (PE) CO2 monitoring during
      surgical procedures in 30 paediatric patients, ranging in age from 6 months to 15
      years (6.15 +/- 4.35 years) and in weight from 4.7 to 73 kg (24.9 +/- 18.2 kg).
      METHODS: Following calibration and an equilibration time for the TcCO2 monitor,
      arterial blood gas samples were obtained as clinically indicated. A total of 64
      sample sets (PaCO2, PECO2 and TcCO2) were obtained from the 30 patients. RESULTS:
      The PECO2 to PaCO2 difference was 0.6-0.9 kPa (4.4 +/- 7.1 mmHg) while the TcCO2
      to PaCO2 difference was 0.36-0.38 kPa (2.8 +/- 2.9 mmHg) (P=NS). The difference
      between the PaCO2 and PECO2 was 0.4 kPa (3 mmHg) or less in 37 of 64 sample sets
      while the difference between the PaCO2 and TcCO2 was 0.4 kPa (3 mmHg) or less in
      49 of 64 sample sets (P=0.038). Linear regression analysis of PECO2 vs. PaCO2
      revealed a slope of 0.434, r=0.8761, r2=0.7676. Linear regression analysis of
      TcCO2 vs. PaCO2 revealed a slope of 0.914, r=0.9472, r2=0.8972. CONCLUSIONS:
      Although in most circumstances, both noninvasive monitors of PCO2 provided a
      clinically acceptable estimate of PaCO2, TCCO2 provided a slightly more accurate
      estimate of PaCO2 during intraoperative anaesthetic care in children.

PMID- 11849577
TI  - Effect of general and epidural anaesthesia on thyroid hormones and immunity in
      neonates.
AB  - BACKGROUND: The aim of this study was to verify if variations of thyroid hormones
      related to circumstances of delivery and mode of maternal anaesthesia can
      contribute to neonatal neutrophil respiratory burst and natural killer cell
      activity. METHODS: We evaluated 10 infants born by vaginal delivery (group A), 10
      infants born by caesarean section after epidural anaesthesia with lidocaine
      (group B) and 10 infants born by caesarean section after general anaesthesia with
      sevoflurane (group C). RESULTS: A significant reduction of neutrophil respiratory
      burst test was found in groups A and C compared with group B. Natural killer cell
      (NK) activity with an effector : target ratio of 30 : 1 (NK30) and 10 : 1 (NK10)
      was significantly higher in group A compared with the B and C groups. In
      addition, thyroid stimulating hormone (TSH) concentration was significantly
      reduced in group A compared with the B and C groups. A significant negative
      correlation was found between TSH and NK30 or NK10. CONCLUSIONS: Our results
      suggest that the mode of delivery and anaesthesia can significantly modify the
      endocrine-immune system in the newborn. Caesarean section delivery with regional
      anaesthesia seems to produce fewer modifications of neonatal immune function
      compared with general anaesthesia.

PMID- 11849576
TI  - The efficacy of caudal ropivacaine 1, 2 and 3 mg x l(-1) for postoperative
      analgesia in children.
AB  - BACKGROUND: The aim of this double blind, randomized, comparative study was to
      assess the analgesic efficacy and incidence of motor block after caudal block
      using three different concentrations of ropivacaine, 1, 2 and 3 mg x l(-1), in
      children 4-12-year-old. METHODS: One hundred and ten children ASA I-II, scheduled
      for inguinal surgery, were included in the study. After induction of a
      standardized general anaesthetic technique, all patients received 1 ml x kg(-1)
      of the ropivacaine solution for a caudal block and were assessed for 8 h after
      the injection. RESULTS: The ropivacaine was well tolerated in all patients.
      Median time to treatment with analgesics was 3.3, 4.5 and 4.2 h in the 1, 2 and 3
      mg x ml(-1) groups, respectively. During the first 4 h, the pain scores for both
      a 6-graded faces scale and a 4-graded observer scale were higher in the 1 mg x
      ml(-1) group than the 3 mg x ml(-1) group. The median sensory block reached T12
      in all groups 1 h after the caudal block. Thereafter, the speed of regression was
      correlated with the ropivacaine concentration. In the patients with a sensory
      block from T12 and above, the median time to treatment with analgesics was longer
      than in the children with a sensory block below T12. The incidence of motor block
      was 28% in the 3 mg x ml(-1) group in comparison with 0 and 13% in the 1 and 2 mg
      x ml(-1) groups. CONCLUSIONS: It was concluded that 1 ml x kg(-1) of ropivacaine
      2 mg x ml(-1) for caudal block provided satisfactory postoperative pain relief
      after inguinal surgery in 4-12-year-old children. Ropivacaine 1 mg x ml(-1)
      showed less efficacy while the use of ropivacaine 3 mg x ml(-1) was associated
      with a higher incidence of motor block with minimal improvement in postoperative
      pain relief.

PMID- 11849578
TI  - Motion sickness and postoperative vomiting in children.
AB  - BACKGROUND: Motion sickness is considered an important risk factor for
      postoperative nausea and vomiting in children. The aim of this study was to
      verify the impact of motion sickness on the incidence of vomiting after routine
      surgery in children, and to compare the incidence of vomiting, after combined
      regional/general anaesthesia, using either halothane or sevoflurane. METHODS: We
      prospectively studied 420 children (369 males and 51 females) who received
      general anaesthesia and inguinal field block for common paediatric surgery. The
      children were randomly allocated into one of two groups (halothane or
      sevoflurane). In the 200 children in the first group (H), general anaesthesia was
      induced and maintained with halothane, whereas in the 220 children in the second
      group (S), anaesthesia was induced and maintained with sevoflurane. RESULTS:
      There were 79 children with a prior history of motion sickness (MS+) and 341
      without such a history (MS-). In the MS+ population, the incidence of vomiting
      was similar in both H and S groups, being around 33%. However, repeated episodes
      of vomiting in MS+ children were more frequent when halothane was used. In the MS
      group, the incidence of vomiting was significantly greater in the H group (19%)
      than in the S group (8%). CONCLUSIONS: In the postoperative period, we found that
      MS+ children vomit more than MS- children, regardless of the inhalation
      anaesthetic used. However, MS- children displayed a higher incidence of vomiting
      when halothane was used rather than sevoflurane.

PMID- 11849579
TI  - Single lung ventilation in children using a new paediatric bronchial blocker.
AB  - As video-assisted thoracoscopic surgery has become more common in paediatric
      patients, the use of single lung ventilation in children has also increased.
      Single lung ventilation in young children is performed by either advancing a
      tracheal tube into the mainstem bronchus opposite the side of surgery or by
      positioning a bronchial blocker into the mainstem bronchus on the operative side.
      Techniques for placing a variety of bronchial blockers outside the tracheal tube
      have been described. We describe a technique for placement of a new bronchial
      blocker through an indwelling tracheal tube using a multiport adaptor and a
      fibreoptic bronchoscope.

PMID- 11849580
TI  - Anaphylactic shock due to cefuroxime in a patient taking penicillin prophylaxis.
AB  - We report a case of cardiovascular collapse in a homozygous sickle cell patient
      undergoing elective orthopaedic surgery, following the intravenous administration
      of cefuroxime. This patient had no known previous drug allergies. She had been
      taking prophylactic penicillin V on a daily basis, for 10 years and had
      encountered no problems. She had received cefuroxime on at least four previous
      occasions, for the treatment of chest infections, with no reported problems. Her
      serum mast cell tryptase, 1 h after the onset of anaphylaxis, was greater than
      200 microg x l(-1) (normal range 10-16). She was skin prick tested, 6 weeks after
      the event, to all the drugs administered during the course of the anaesthetic and
      reacted positively only to cefuroxime. Specific IgE levels for penicillin
      determinants and latex were negative (13 and 0 IU x ml(-1), respectively UniCAP
      Pharmacia & Upjohn).

PMID- 11849581
TI  - Tetralogy of Fallot with absent pulmonary valve: a case complicated by bilateral
      relapsing pneumothorax.
AB  - We report a case of a neonate with tetralogy of Fallot with aneurysmal dilatation
      of the pulmonary artery, complicated by bilateral relapsing pneumothorax. The
      relapsing air leak made it necessary to place up to five chest drains and to
      switch from conventional ventilation to high frequency ventilation. In the course
      of 30 days, all drains were removed. Once other anatomical and functional
      malformations of the respiratory system had been appropriately excluded and
      reasonable haemodynamic stability had been achieved, the patient underwent
      successful radical corrective heart surgery in hypothermia and cardioplegia. We
      emphasize the advantage of resolving respiratory failure preoperatively to
      guarantee the success of corrective heart surgery and treatment of other
      surgically severe cases.

PMID- 11849582
TI  - Anaesthetic management of a case of nesidioblastosis for subtotal pancreatectomy.
AB  - Hyperinsulinism is a rare cause of severe persistent hypoglycaemia in the
      neonatal period. It is associated with a high incidence of brain damage and
      mental retardation as a consequence of repeated episodes of hypoglycaemia.
      Subtotal to near total pancreatectomy is indicated as a matter of urgency to
      decrease the amount of circulating insulin. The perioperative management of a 45
      day-old, 5 kg male infant with hyperinsulinaemia (nesidioblastosis) is described.
      He had a history of generalized tonic clonic seizures 4 h after birth. The blood
      sugar at that time was 0.66 mmol x l(-1) (12 mg x dl(-1)) and serum calcium was
      2.4 mmol x l(-1) (9.82 mg x dl(-1)). The insulin : glucose ratio was 1.6 (normal
      < 0.4). Occasional episodes of hypoglycaemia persisted in spite of medical line
      of management with intravenous dextrose 12%, 2 h gastric tube feeds,
      hydrocortisone (5 mg x kg(-1) x day(-1) i.v.) and oral diazoxide 10 mg x kg(-1),
      8 h for 3 weeks. A CT scan and USG did not reveal any abnormality of the
      pancreas. However, the EEG varied from one of abnormally low amplitude to an
      isoelectric record. Renal, liver function tests and coagulation profile were
      normal. The patient was scheduled for elective subtotal pancreatectomy. The
      anaesthetic management with emphasis on glucose homeostasis and fluid balance is
      discussed.

PMID- 11849583
TI  - Adjunctive peribulbar anaesthesia for paediatric ophthalmic surgery: are the
      risks justified?

PMID- 11849585
TI  - Local anaesthesia toxicity is additive: a concern for neonatal caudal
      anaesthesia?

PMID- 11849587
TI  - An unusual cause of difficulty in changing the tracheal tube.

PMID- 11849588
TI  - Inadvertent i.v. bolus injection of ropivacaine in a 30-month-old child.

PMID- 11849589
TI  - Rapid sequence induction for penetrating head injury from a chopstick in a
      paediatric patient.

PMID- 11849590
TI  - Graft transmission of induced and spontaneous post-transcriptional silencing of
      chitinase genes.
AB  - Sense and antisense tobacco chitinase (CHN) transgenes, Luciferase-CHN
      transcriptional fusions, and promoterless CHN cDNAs were introduced biolistically
      into CHN transformants of tobacco that never exhibit spontaneous gene silencing.
      All of the constructs tested induced systemic silencing of the resident CHN
      transgene and endogenes. Nuclear run-on transcription assays showed that local
      introduction of additional gene copies triggers systemic post-transcriptional
      gene silencing (PTGS). Together, this provides evidence that additional transgene
      copies need not be either highly transcribed or produce sense transcripts to
      evoke production of systemic PTGS signals. CHN PTGS was transmitted by top
      grafting, but not by reciprocal grafting of mature stems or the exchange of
      tissue plugs. Thus, the commonly encountered difficulties in achieving graft
      transmission could reflect the method used. Silencing in sense but not antisense
      transformants was transmitted by grafting to a high-expressing sense CHN scion
      suggesting that the elaboration of mobile signals may not be an essential feature
      of antisense-mediated gene silencing.

PMID- 11849591
TI  - Transactivation of BARNASE under the AtLTP1 promoter affects the basal pole of
      the embryo and shoot development of the adult plant in Arabidopsis.
AB  - Genetically controlled expression of a toxin provides a tool to remove a specific
      structure and consequently study its role during a developmental process. The
      availability of many tissue-specific promoters is a good argument for the
      development of such a strategy in plants. We have developed a conditional system
      for targeted toxin expression and demonstrated its use for generating embryo
      phenotypes that can bring valuable information about signalling during
      embryogenesis. The BARNASE gene was expressed in the Arabidopsis embryo under the
      control of two promoters, one from the cyclin AtCYCB1 gene and one from the
      AtLTP1 gene (Lipid Transfer Protein 1). One-hundred percent seed abortion was
      obtained with the cyclin promoter. Surprisingly however, the embryos displayed a
      range of lethal phenotypes instead of a single arrested stage as expected from
      this promoter. We also show that BARNASE expression under the control of the
      AtLTP1 promoter affects the basal pole of the globular embryo. Together with
      reporter expression studies, this result suggests a role of the epidermis in
      controlling the development of the lower tier of the embryo. This defect was not
      embryo-lethal and we show that the seedlings displayed a severe shoot phenotype
      correlated to epidermal defects. Therefore, the epidermis does not play an active
      role during organogenesis in seedlings but is important for the postgermination
      development of a viable plant.

PMID- 11849592
TI  - The K+ channel SKT1 is co-expressed with KST1 in potato guard cells--both
      channels can co-assemble via their conserved KT domains.
AB  - An appreciable number of potassium channels mediating K+ uptake have been
      identified in higher plants. Promoter-beta-glucuronidase reporter gene studies
      were used here to demonstrate that SKT1, encoding a potato K+ inwardly rectifying
      channel, is expressed in guard cells in addition to KST1 previously reported.
      However, whereas KST1 was found to be expressed in essentially all mature guard
      cells, SKT1 expression was almost exclusively restricted to guard cells of the
      abaxial leaf epidermis. This suggests that different types of K+ channel subunits
      contribute to channel formation in potato guard cells and therefore differential
      regulation of stomatal movements in the two leaf surfaces. The overlapping
      expression pattern of SKT1 and KST1 in abaxial guard cells indicates that K+in
      channels of different sub-families contribute to ionic currents in this cell
      type, thus explaining the different properties of channels expressed solely in
      heterologous systems and those endogenous to guard cells. Interaction studies had
      previously suggested that plant K+ inward rectifiers form clusters via their
      conserved C-terminal domain, KT/HA. K+ channels co-expressed in one cell type may
      therefore form heteromers, which increase functional variability of K+ currents,
      a phenomenon well described for animal voltage-gated K+ channels. Co-expression
      of KST1 and SKT1 in Xenopus oocytes resulted in currents with an intermediate
      sensitivity towards Cs+, suggesting the presence of heteromers, and a sensitivity
      towards external Ca2+, which reflected the property of the endogenous K+in
      current in guard cells. Modulation of KST1 currents in oocytes by co-expressing
      KST1 with a SKT1 pore-mutant, which by itself was not able to confer activating
      K+ currents, demonstrated the possibility that KST1 and SKT1 co-assemble to
      hetero-oligomers. Furthermore, various C-terminal deletions of the mutated SKT1
      channel restored KST1 currents, showing that the C-terminal KT motif is essential
      for heteromeric channel formation.

PMID- 11849594
TI  - Control of flowering time by FLC orthologues in Brassica napus.
AB  - FLOWERING LOCUS C (FLC) in Arabidopsis encodes a dosage dependent repressor of
      flowering. We isolated five FLC-related sequences from Brassica napus (BnFLC1-5).
      Expression of each of the five sequences in Arabidopsis delayed flowering
      significantly, with the delay in flowering time ranging from 3 weeks to more than
      7 months, relative to the flowering time of 3 weeks in untransformed Ler. In the
      reciprocal experiment, expression of Arabidopsis FLC (AtFLC) in an early
      flowering B. napus cultivar delayed flowering by 2-6 weeks, confirming the
      requirement of this gene for floral repression. In B. napus, we show that late
      flowering and responsiveness to vernalization correlate with the level of BnFLC
      mRNA expression. The different BnFLC genes show differential expression in
      leaves, stems and shoot tips, but expression is not detectable in roots.
      Vernalization dramatically reduces the level of BnFLC transcript and restores
      early flowering in the winter cultivar Colombus. We conclude that BnFLC genes
      confer winter requirement in B. napus and account for the major vernalization
      responsive flowering time differences in the different cultivars of B. napus in a
      manner analogous to that of AtFLC in Arabidopsis ecotypes.

PMID- 11849593
TI  - Evidence for expression level-dependent modulation of carbohydrate status and
      viral resistance by the potato leafroll virus movement protein in transgenic
      tobacco plants.
AB  - High-level constitutive expression of the cell-to-cell movement protein from the
      phloem-restricted potato leafroll virus (PLRV-MP17) in transgenic tobacco plants
      leads to growth retardation and severe phenotypic changes of source leaves
      paralleled by a drastic accumulation of soluble sugars and starch (Herbers et
      al., 1997). To investigate whether the MP17-induced alteration in carbon
      metabolism is related to the targeting and modification of specific plasmodesmata
      (Pd) or is rather due to pleiotropic effects caused by high MP17 protein amounts,
      non-phenotypic tobacco plants expressing a MP17:GFP fusion protein were obtained
      and compared with previously described MP17 transgenic lines. Confocal laser
      scanning microscopy and immunogold labelling studies revealed an overall affinity
      of MP17 to Pd in vascular and non-vascular tissue of source leaves, whereas in
      sink leaves GFP fluorescence was restricted to Pd of trichomes. In source leaves,
      plasmodesmal size exclusion limits of mesophyll cells were likewise increased by
      MP17 and MP17:GFP independent from steady-state levels of the protein amount and
      phenotypic alteration. Conversely, carbohydrate contents in source leaves
      strictly correlated with quantified MP17 protein levels. Low expression of MP17
      and MP17:GFP decreased soluble sugars and starch contents in leaves possibly due
      to changes in plasmodesmal permeability while increasing MP17 protein levels led
      to carbohydrate accumulation and a stunted growth. Infection of transgenic lines
      with the unrelated potato virus Y (PVY)N revealed an expression level-dependent
      mode of MP17-mediated resistance. Phenotypic changes and carbohydrate-mediated
      defence responses as indicated by elevated levels of PR-protein transcripts were
      crucial for increased viral resistance, whereas plasmodesmal targeting and
      modification by MP17 per se had either no effect or even increased susceptibility
      to PVY. Thus, our results implicate that the absolute level of expression needs
      to be critically considered when elucidating the effect of MPs on carbon
      metabolism, biomass allocation and virus resistance.

PMID- 11849595
TI  - Novel ABA- and dehydration-inducible aldehyde dehydrogenase genes isolated from
      the resurrection plant Craterostigma plantagineum and Arabidopsis thaliana.
AB  - In order to identify genes that are critical for the ABA-dependent stress
      response in the resurrection plant Craterostigma plantagineum, a gene was
      isolated with homology to class 3 variable substrate aldehyde dehydrogenases
      (ALDH). The C. plantagineum gene Cp-ALDH constitutes a novel class of plant
      ALDHs. In a search for corresponding genes from Arabidopsis thaliana, Ath-ALDH3
      and Ath-ALDH4 were isolated, showing 70% and 80% similarity to Cp-ALDH.
      Phylogenetically, the Cp- and Ath-ALDH3 and -ALDH4 proteins are closely related
      to aldehyde dehydrogenases from bacteria and mammalian species and are separated
      from known plant ALDHs and betaine-aldehyde dehydrogenases (BADH). Cp-ALDH
      transcript and polypeptide are up-regulated in vegetative tissues and callus in
      response to dehydration or ABA-treatment. Ath-ALDH3 expression was induced in
      response to dehydration and ABA treatment, while Ath-ALDH4 is constitutively
      expressed at a low level. Recombinant Cp-ALDH protein oxidizes nonanal,
      propionaldehyde and acetaldehyde, with Km values of 2.2 microm, 0.27 mm and 3.23
      mm, respectively, in an NAD-dependent manner. Immunogold electron microscopy
      shows that Cp-ALDH is localized in plastids.

PMID- 11849596
TI  - Sub-cellular localisation of GFP-tagged tobacco mitotic cyclins during the cell
      cycle and after spindle checkpoint activation.
AB  - We have previously shown that the tobacco cyclin B1;1 protein accumulates during
      the G2 phase of the cell cycle and is subsequently destroyed during mitosis.
      Here, we investigated the sub-cellular localisation of two different B1-types and
      one A3-type cyclin during the cell cycle by using confocal imaging and
      differential interference contrast (DIC) microscopy. The cyclins were visualised
      as GFP-tagged fusion proteins in living tobacco cells. Both B1-type cyclins were
      found in the cytoplasm and in the nucleus during G2 but when cells entered into
      prophase, both cyclins became associated with condensing chromatin and remained
      on chromosomes until metaphase. As cells exited metaphase, the B1-type cyclins
      became degraded, as shown by time-lapse images. A stable variant of cyclin B1;1
      GFP fusion protein, in which the destruction box had been mutated, maintained its
      association with the nuclear material at later phases of mitosis such as anaphase
      and telophase. Furthermore, we demonstrated that cyclin B1;1 protein is
      stabilised in metaphase-arrested cells after microtubule destabilising drug
      treatments. In contrast to the B1-type cyclins, the cyclin A3;1 was found
      exclusively in the nucleus in interphase cells and disappeared earlier than the
      cyclin B1 proteins during mitosis.

PMID- 11849597
TI  - A tobacco nuclear extract supporting transcription, processing, splicing and
      modification of plant intron-containing tRNA precursors.
AB  - Nuclear tRNA genes are transcribed by RNA polymerase III (Pol III) and pre-tRNAs
      are processed into mature tRNAs via complex processes in the nucleus. We have
      developed an in vitro Pol III-dependent transcription system derived from tobacco
      cultured cells, which supports efficiently not only transcription of a variety of
      plant tRNA genes but also 5'-and 3'-end processing, nucleotide modification and
      splicing of intron-containing pre-tRNAs. The structures of in vitro transcripts
      have been confirmed by primer extension analysis and by RNase T1 fingerprinting.
      The optimal Mg2+ concentration differed for each step so that each reaction can
      be controlled by adjusting the Mg2+ concentration. At 1 mm Mg2+, only
      transcription occurs so that pre-tRNAs accumulate. The splicing reaction can be
      initiated by raising Mg2+ ions (> 5 mm) and enhanced by adding 1 mm
      hexamminecobalt chloride. Using the optimized system for the Nicotiana intron
      containing tRNATyr gene, the precise initiation and termination sites of
      transcription and the splice sites were determined. The presence of 1 mm NAD+ in
      the reaction mixture leads to the removal of the 2' phosphate at the splice
      junction of tRNATyr, demonstrating the activity of a 2'-phosphotransferase in the
      tobacco nuclear extract. Many modified nucleosides such as m2G, m22G, m1A, phi27
      and phi35 are introduced in either of the studied transcripts. As shown in other
      systems, the conversion of U35 to phi requires an intron-containing substrate.

PMID- 11849602
TI  - Modular motor learning.
AB  - An interesting theory of sensorimotor control has been recently extended and
      simulated. The simulation can learn to control an arm in several mutually
      exclusive 'contexts', situations where the arm carries one of four objects with
      different mechanical properties. It provides a good theoretical framework for
      testing biological motor systems.

PMID- 11849598
TI  - Towards functional proteomics of membrane protein complexes: analysis of
      thylakoid membranes from Chlamydomonas reinhardtii.
AB  - Functional proteomics of membrane proteins is an important tool for the
      understanding of protein networks in biological membranes but structural studies
      on this part of the proteome are limited. In this study we undertook such an
      approach to analyse photosynthetic thylakoid membranes isolated from wild-type
      and mutant strains of Chlamydomonas reinhardtii. Thylakoid membrane proteins were
      separated by high-resolution two-dimensional gel electrophoresis (2-DE) and
      analysed by immuno-blotting and mass spectrometry for the presence of membrane
      spanning proteins. Our data show that light-harvesting complex proteins (LHCP),
      that cross the membrane with three transmembrane domains, can be separated using
      this method. We have identified more than 30 different LHCP spots on our gels.
      Mass spectrometric analysis of 2-DE separated Lhcb1 indicates that this major
      LHCII protein can associate with the thylakoid membrane with part of its putative
      transit sequence. Separation of isolated photosystem I (PSI) complexes by 2-DE
      revealed the presence of 18 LHCI protein spots. The use of two peptide-specific
      antibodies directed against LHCI subunits supports the interpretation that some
      of these spots represent products arising from differential processing and post
      translational modifications. In addition our data indicate that the reaction
      centre subunit of PSI, PsaA, that possesses 11 transmembrane domains, can be
      separated by 2-DE. Comparison between 2-DE maps from thylakoid membrane proteins
      isolated from a PSI-deficient (Deltaycf4) and a crd1 mutant, which is
      conditionally reduced in PSI and LHCI under copper-deficiency, showed the
      presence of most of the LHCI spots in the former but their absence in the latter.
      Our data demonstrate that (i) hydrophobic membrane proteins like the LHCPs can be
      faithfully separated by 2-DE, and (ii) that high-resolution 2-DE facilitates the
      comparative analysis of membrane protein complexes in wild-type and mutants
      cells.

PMID- 11849603
TI  - Are psychology's tribes ready to form a nation?
AB  - Collaboration between social psychologists and cognitive neuroscientists is
      giving rise to a new approach that its practitioners call 'social cognitive
      neuroscience'. Scientists from each discipline are using the theories and
      techniques of the other to generate new answers to fundamental questions about
      attitudes, beliefs, the self, moral judgment, and other issues. Is this
      interdisciplinary endeavor an exercise in wishful thinking and good intentions,
      or is it a preview of psychology's future?

PMID- 11849604
TI  - A new direction for population vectors.

PMID- 11849605
TI  - Memories bound: the neuroscience of dreams.

PMID- 11849606
TI  - Secondary representation: continued...

PMID- 11849608
TI  -  Neuroecologists' are not made of straw.

PMID- 11849609
TI  - Everything in neuroecology makes sense in the light of evolution. Response from
      Bolhuis and Macphail.

PMID- 11849610
TI  - A saliency map in primary visual cortex.
AB  - I propose that pre-attentive computational mechanisms in primary visual cortex
      create a saliency map. This map awards higher responses to more salient image
      locations; these responses are those of conventional V1 cells tuned to input
      features, such as orientation and color. Hence no separate feature maps, or any
      subsequent combination of them, is needed to create a saliency map. I use a model
      to show that this saliency map accounts for the way that the relative
      difficulties of visual search tasks depend on the features and spatial
      configurations of targets and distractors. This proposal links psychophysical
      behavior to V1 physiology and anatomy, and thereby makes testable predictions.

PMID- 11849611
TI  - Functional and dynamic properties of visual peripersonal space.
AB  - In order to code visual peripersonal space, human and non-human primates need an
      integrated system that controls both visual and tactile inputs within
      peripersonal space around the face and the hand, based on visual experience of
      body parts. The existence of such a system in humans has been demonstrated, and
      there is evidence showing that visual peripersonal space relating to the hand has
      important dynamic properties, for example, it can be expanded and contracted
      depending on tool use. There is also evidence for a high degree of functional
      similarity between the characteristics of the visual peripersonal space in humans
      and in monkeys.

PMID- 11849613
TI  - Synthesis of autonomous robots through evolution.
AB  - Evolutionary robotics is the attempt to develop robots through a self-organized
      process based on artificial evolution. This approach stresses the importance of
      the study of systems that have a body and that are situated in a physical
      environment, and which autonomously develop their own skills in close interaction
      with the environment. In this review we briefly illustrate the method and the
      main concept of evolutionary robotics, and examine the most significant
      contribution in this area. We also discuss some of the contributions that this
      research area is making to the foundational debate in cognitive science.

PMID- 11849612
TI  - Sleep imaging and the neuro-psychological assessment of dreams.
AB  - Recent neuroimaging studies show that human rapid-eye-movement (REM) sleep is
      characterized by a specific pattern of regional brain activity. Although this is
      usually interpreted in relation to physiological and cellular mechanisms, the
      specific regional distribution of brain activity during REM sleep might also be
      linked to specific dream features. Remarkably, several bizarre features of normal
      dreams have similarities with well-known neuropsychological syndromes after brain
      damage, such as delusional misidentifications for faces and places. We propose
      that neuropsychological analysis of dream content might offer new ways of
      interpreting neuroimaging maps of sleep, and make specific predictions for future
      neuroimaging studies.

PMID- 11849614
TI  - Structure and function of auditory cortex: music and speech.
AB  - We examine the evidence that speech and musical sounds exploit different acoustic
      cues: speech is highly dependent on rapidly changing broadband sounds, whereas
      tonal patterns tend to be slower, although small and precise changes in frequency
      are important. We argue that the auditory cortices in the two hemispheres are
      relatively specialized, such that temporal resolution is better in left auditory
      cortical areas and spectral resolution is better in right auditory cortical
      areas. We propose that cortical asymmetries might have developed as a general
      solution to the need to optimize processing of the acoustic environment in both
      temporal and frequency domains.

PMID- 11849615
TI  - The conscious access hypothesis: origins and recent evidence.
AB  - Consciousness might help to mobilize and integrate brain functions that are
      otherwise separate and independent. Evidence for this 'conscious access
      hypothesis' was described almost two decades ago, in a framework called global
      workspace theory. The theory had little impact at first, for three reasons:
      because consciousness was controversial; the evidence, though extensive, was
      indirect; and integrative theory was unfashionable. Recent neuroimaging evidence
      appears broadly to support the hypothesis, which has implications for perception,
      learning, working memory, voluntary control, attention and self systems in the
      brain.

PMID- 11849616
TI  - Breaking out of old reading habits.

PMID- 11849617
TI  - Evaluation of five methods for determining low-density lipoprotein cholesterol
      (LDL-C) in hemodialysis patients(1).
AB  - OBJECTIVES: Current recommendations for the management of dyslipidemia are
      largely based on the concentration of LDL-C. Most clinical laboratories estimate
      the concentration of LDL-C by the recommended routine method, the equation of
      Friedewald, in specimens from fasting subjects and with TG concentrations < 4.52
      mmol/L. Because of the limitations of the Friedewald calculation, direct methods
      for an accurate quantification of LDL-C are needed. DESIGN AND METHODS: In the
      present study we evaluated the accuracy of the following 5 different procedures
      for LDL-C in 98 patients on hemodialysis: the Friedewald equation, where LDL-C is
      calculated from HDL-C, measured either by the precipitation procedure with
      dextran sulfate-Mg(2+) (Method 1), or by a direct HDL-C assay (Method 2), the
      Direct LDL assay (Method 3), the homogeneous N-geneous LDL assay (Method 4) and
      the calculated LDL-C values deriving from the ApoB based equation: 0.41TC -
      0.32TG + 1.70ApoB - 0.27, (Clin Chem 1997;43:808-815) (Method 5). RESULTS: All
      five LDL-C methods were found to be in good agreement with
      ultracentrifugation/dextran sulfate-Mg(2+) precipitation with the coefficients of
      correlation of the assays to ranging between 0.93-0.95. However, significant
      differences in the mean values and biases vs. the reference method were observed.
      The Friedewald equation and the Direct assay were less affected by high LDL-C
      levels, and they presented higher sensitivity and higher negative predictive
      value. The N-geneous assay and the ApoB derived calculation were less affected by
      high triglyceride levels, and they presented higher specificity and higher
      positive predictive value. At the diagnostic LDL-C level of 3.37 mmol/L, both
      Friedewald calculations correctly classified 82/92 patients; Direct assay 86/98;
      N-geneous assay 88/98; and ApoB derived calculation 88/98. At the diagnostic LDL
      C level of 2.98 mmol/L, Friedewald calculations (Method 1 and Method 2) correctly
      classified 82/92 and 81/92 patients, respectively; Direct assay (LDL-3) 87/98; N
      geneous assay (LDL-4) 91/98; and ApoB derived calculation (LDL-5) 91/98.
      CONCLUSIONS: Among hemodialysis patients, who commonly present "average" LDL-C
      concentrations and high TG levels, the N-geneous assay and the apoB derived
      calculation seem to yield more acceptable results for the estimation of LDL-C.

PMID- 11849618
TI  - Competition of tamoxifen with thyroxine for TBG binding: ligand binding assay and
      computational data.
AB  - OBJECTIVE: Tamoxifen, a nonesteroidal antiesterogen, is widely used in the
      treatment of breast cancer. Recently, the effect of tamoxifen on thyroid function
      has caused considerable concern, yet the results of different studies are
      controversial and the precise mechanism of such influence is obscure. In view of
      the fact that some drugs such as furosemide, diclofenac and mefenamic acid, based
      on the structural similarities to thyroxine could compete for binding to
      thyroxine binding globulin (TBG) and appears that there are some structural
      similarities between tamoxifen and thyroxine, one can hypothesize that tamoxifen
      is also able to compete for TBG binding and thereby affecting thyroid function
      tests. DESIGN AND METHODS: In this study, we designed an in vitro binding assay
      as well as computational methods using MOPAC 7 package for evaluation of
      competitive potency of tamoxifen for TBG binding in comparison with well-known
      TBG competitors (including furosemide, mefenamic acid and diclofenac). RESULTS:
      The result of competition assay and Scatchard analysis revealed that tamoxifen
      does not bind to TBG at the T4 binding site, thus it is not a thyroxine
      competitor. Computational results also indicated that structural characteristics
      of tamoxifen are significantly different from those of T4 and its well-known
      competitors. CONCLUSION: In conclusion, the probability of competition between
      tamoxifen and T4 is ruled out by these results.

PMID- 11849619
TI  - Development and evaluation of assays for the determination of total and
      pancreatic amylase at 37 degrees C according to the principle recommended by the
      IFCC.
AB  - OBJECTIVES: The aim of our study was a) to optimize assays for measurement of
      total (T-) and pancreatic (P-)amylase at 37 degrees C based on the principle
      recommended by the IFCC at 30 degrees C, b) to evaluate the analytical
      performance of these assays in a multicentric study and c) to establish reference
      intervals for serum and urine for either method. METHODS: Optimized conditions
      for 37 degrees C were elaborated with regard to substrate concentration, pH,
      inorganic additives and glucosidase activity. The cleavage pattern of the EPS
      substrate was studied by HPLC. Liquid ready-to-use reagents for T- and P-amylase
      were provided to six European laboratories. RESULTS: The assays showed good
      performance characteristics (median intraassay CVs 1.0% for T- and 1.3% for P
      amylase, median interassay CVs 3.0% for either assay, dynamic range 15-fold URL
      for T- and 30-fold for P-amylase), high correlation with the previous EPS methods
      (r > 0.996, slope 0.43, intercept < 5 U/L) in serum, heparin plasma and urine and
      good analytical specificity of the P-amylase assay (residual S-amylase activity
      2.4%). Serum reference ranges were found to be 28 to 100 U/L for T- and 13 to 53
      U/L for P-amylase (n = 775); URLs in urine were estimated as 490 U/L or 280 U/g
      creatinine for males and 450 U/L or 380 U/g creatinine for females with total
      amylase. CONCLUSION: We believe that these assays based on the 30 degrees C IFCC
      recommendation represent a further improvement in amylase methodology at 37
      degrees C and merit broad application in clinical routine.

PMID- 11849620
TI  - The biosynthesis of prostate-specific antigen in non prostatic cell lines.
AB  - The biosynthesis of prostate specific antigen (PSA) was studied in human
      epidermoid carcinoma, (KB) cells and in normal human embryonic lung (WI-38)cells.
      The prostate carcinoma cell line, PC-35F12 was used as a control. PSA specific
      antibodies were used to precipitate the immunologically reactive peptides from
      cell extracts and conditioned media. The immunoprecipitates were analyzed by
      electrophoresis followed by fluorgraphy. Human PSA is initially synthesized as 32
      kDa secretory glycopeptide containing one N-linked oligosaccharide and then
      processed to a 34-kDa secretory glycoprotein in KB cells. PSA is also expressed
      in normal human embryonic lung cells, WI-38. These results confirm that PSA
      expression is not prostate specific, but is also found in some nonprostatic
      cells. From these results, we conclude that PSA may play an important physiologic
      role in several tissues.

PMID- 11849621
TI  - Plasma ascorbic acid: measurement, stability and clinical utility revisited.
AB  - AIMS: To compare plasma ascorbic acid results by the colorimetric FRASC (Ferric
      Reducing/Antioxidant and Ascorbic Acid) assay and a reference HPLC method; to re
      examine plasma ascorbic acid stability, and anticoagulant effect. DESIGN AND
      METHODS: For method comparison, 31 plasma samples were tested by both methods.
      For stability, matching EDTA, heparin, citrate and fluoride/oxalate plasma,
      stored under different conditions of time and temperature, was measured. RESULTS:
      FRASC is an acceptable alternative to HPLC for plasma ascorbic acid: precision,
      limit of detection and recovery were similar, and results by the two methods were
      indistinguishable: mean (95% CI) difference:1.8 (-1.1-4.6; n = 31) micromol/L.
      Ascorbic acid was most stable in heparinized plasma. Marked loss (p < 0.05) in
      EDTA plasma occurred within 30 min of blood collection. CONCLUSIONS: FRASC offers
      a speedy and reliable alternative to HPLC for plasma ascorbic acid. Heparin is
      proposed as the anticoagulant of choice; loss of ascorbic acid is rapid in EDTA
      plasma ex vivo.

PMID- 11849622
TI  - Effects of tobacco smoking on plasma selenium, zinc, copper and iron
      concentrations and related antioxidative enzyme activities.
AB  - OBJECTIVES: The aim of the study was to investigate whether alterations in
      antioxidative enzyme activities are dependent on their cofactor concentrations in
      tobacco smokers. DESIGN AND METHODS: Plasma selenium, copper, zinc and iron
      concentrations, and the activities of related erythrocyte antioxidative enzymes
      copper-zinc superoxide dismutase (Cu-Zn SOD), catalase (CAT) and glutathione
      peroxidase (GSH-Px) were measured in tobacco smokers and compared with those of
      nonsmokers. Plasma thiocyanate levels were measured as an index of smoking
      status. RESULTS: While plasma copper concentration and erythrocyte Cu-Zn SOD
      activity were significantly higher, plasma selenium concentration and erythrocyte
      GSH-Px activities were significantly lower in tobacco smokers than in nonsmokers.
      There was no significant difference in plasma iron and zinc concentrations or
      erythrocyte CAT activity between the two groups. There were significant positive
      correlations between erythrocyte GSH-Px and plasma selenium levels, between Cu-Zn
      SOD and copper levels, and between CAT and iron levels, and a negative
      correlation between plasma thiocyanate and selenium content in tobacco smokers.
      CONCLUSIONS: These findings suggest that antioxidative enzyme activities change
      depending on their cofactor concentrations in tobacco smokers.

PMID- 11849623
TI  - Characterization of plasma acylcarnitines in patients under valproate monotherapy
      using ESI-MS/MS.
AB  - OBJECTIVES: The effect of administration of the antiepileptic drug valproate
      (VPA), on the composition of the plasma acylcarnitine profile (including free
      carnitine) was investigated. DESIGN AND METHODS: Plasma samples were obtained
      from 18 individuals (13 males:5 females; 15-65 y) on long-term treatment with VPA
      (resulting in plasma levels of 14.6-135.0 mg/L; therapeutic conc.: 40-100 mg/L).
      Acylcarnitines (AC) in plasma were quantified by electrospray tandem mass
      spectrometry (ESI-MS/MS). RESULTS: VPA was found to increase the levels (mean +/-
      SD, microM) of 3-hydroxy-isovalerylcarnitine (0.10 +/- 0.04; controls: 0.02
      0.06), C14:2 acylcarnitine (0.11 +/- 0.05; controls: 0.02-0.08),
      propylglutarylcarnitine (0.06 +/- 0.05; controls: 0.00-0.04), and C18-0H
      acylcarnitine (0.09 +/- 0.05; controls: 0.00-0.04). The free carnitine (C) (42.2
      +/- 9.0; controls: 22.3-54.9) and the total carnitine (52.3 +/- 10.1; controls:
      26.5-73.6) were not significantly altered by VPA. Other AC (C2-C18,
      monounsaturated and hydroxylated) were all within the control range and
      especially no increase of C8 (valproyl) carnitine was observed. A positive
      correlation was found between the ratios [AC] / [C] (p < 0.05) or [long-chain AC
      (C10-C18)] / [C] (p < 0.09) with the plasma VPA concentration. CONCLUSIONS: The
      unequivocal increase in 3-hydroxy-isovalerylcarnitine is consistent with the
      increase of 3-hydroxy-isovaleric acid observed in urine of VPA treated patients.
      This finding suggests an interaction mechanism of VPA with specific enzymes,
      namely involved in leucine metabolism. Adult patients under VPA monotherapy do
      not suffer from carnitine deficiency; the effect of the accumulating
      acylcarnitines is ill-defined.

PMID- 11849624
TI  - Critical differences in the serial measurement of three biochemical markers of
      bone turnover in the sera of pre- and postmenopausal women.
AB  - OBJECTIVES: The purpose of this investigation was to quantify the biologic, day
      to-day variability and critical differences in serum levels of crosslinked
      collagen N-telopeptides (NTx), procollagen aminoterminal extension propeptides
      (PINP) and bone specific alkaline phosphatase (bAP) in healthy women. DESIGN AND
      METHODS: Seven blood samples were collected from 12 pre- and 15 postmenopausal
      women over 4 to 6 months. NTx, PINP and bAP levels were determined utilizing
      enzyme- and radioimmunoassay techniques. RESULTS: The within-subject coefficient
      of variation (C.V.) in serum bAP, NTx and PINP levels was 7.1, 10.6 and 12.4%
      respectively. These variances did not differ significantly among premenopausal
      women when compared with postmenopausal subjects. Combining terms for analytical
      and biologic variability revealed that a critical difference between 2 successive
      serial measurements is 24% for bAP, 34% for NTx and 38% for PINP. CONCLUSION:
      Circulating levels of NTx, PINP and bAP are stable over time periods of several
      months, allowing for the determination of significant changes in skeletal
      metabolism of women.

PMID- 11849625
TI  - Mediators of inflammation in children with type I diabetes mellitus: cytokines in
      type I diabetic children.
AB  - OBJECTIVES: Recent evidence favors primary role of cellular autoimmunity and its
      humoral mediators in pathogenesis and following Type I diabetes mellitus (DM).
      The present study was carried out to investigate serum concentrations of C
      reactive protein (CRP), interleukin (IL)-6, IL-8 and tumor necrosis factor (TNF)
      alpha in children with type I DM. Potential role of lipid metabolism, glycemic
      control, body mass index (BMI) and disease duration were evaluated. DESIGN AND
      METHODS: Thirty-five children with type I DM and 30 age and gender matched
      nondiabetic controls were recruited for this study. RESULTS: Circulating IL-8
      levels were elevated in children with type I DM (12.7 +/- 1.7 pg/mL) compared
      with nondiabetic controls (5.5 +/- 0.3 pg/mL) and the difference remained
      significant after adjustment for cofactors and covariates (p: 0.033). Although
      statistically insignificant serum CRP concentrations were slightly higher in
      diabetic children (p: 0.075). Serum TNF-alpha and IL-6 levels were comparable in
      diabetic and nondiabetic groups. However newly diagnosed (<1 yr) cases had higher
      TNF-alpha and IL-6 levels compared to cases with longer standing DM. In diabetic
      children BMI was independently associated with an increase in serum IL-8 levels.
      Serum CRP, lipids, apolipoproteins and glycemic control were not significant
      predictors of cytokine concentrations in children with type I DM. CONCLUSION:
      Circulating levels of IL-8 were elevated and were correlated with BMI in children
      with type I DM, hinting perhaps at adipose tissue as a site of production.
      Elevated systemic IL-6 and TNF-alpha were limited to newly diagnosed cases
      suggesting activation of the inflammatory immune response system at early stages
      of the disease.

PMID- 11849626
TI  - Quantitative RT-PCR luminometric hybridization assay with an RNA internal
      standard for cytokeratin-19 mRNA in peripheral blood of patients with breast
      cancer.
AB  - OBJECTIVES: To develop a highly sensitive quantitative RT-PCR hybridization assay
      for the determination of CK-19 mRNA in peripheral blood of patients with breast
      cancer. PATIENTS AND METHODS: Quantification of CK-19 mRNA was based on the
      coamplification of CK-19 mRNA with a recombinant CK-19 RNA internal standard (CK
      19 RNA-IS) through RT-PCR. The biotinylated amplification products were
      immobilized on steptavidin coated wells, hybridized with digoxigenin labeled
      probes and determined through an antidigoxigenin antibody conjugated to alkaline
      phosphatase by luminometric detection. The developed luminometric hybridization
      assay was validated with samples containing total RNA of known amounts from CK-19
      expressing cells (MCF-7) in the presence of 1 microg total RNA isolated from
      peripheral blood mononuclear cells (PBMC) of healthy controls and a constant
      amount of CK-19 RNA-IS. The method was applied for the quantitative determination
      of CK-19 mRNA in the peripheral blood of 26 healthy volunteers, 14 patients with
      stage IV breast cancer and 37 patients with stage I/II breast cancer before
      chemotherapy. RESULTS: Luminescence ratios for CK-19 mRNA and CK-19 RNA-IS were
      linearly related to the number of MCF-7 cells within the range of 1 to 2000
      cells. The overall reproducibility of the assay (between-run) varied between 8.9%
      and 13.4%. The method can clearly detect CK-19 mRNA from 1 MCF-7 cell in the
      presence of 10(6) normal PBMC and is highly specific as none of the 26 healthy
      controls tested had detectable CK-19 mRNA levels, while 10 out of 14 (71.4%) and
      9 out of 37 (24.3%) patients with stage IV and stage I/II breast cancer,
      respectively, were tested positive. CONCLUSION: The developed quantitative RT-PCR
      hybridization assay for CK-19 is reproducible, highly sensitive and specific, and
      can be used for a large-scale prospective evaluation of clinical samples.

PMID- 11849627
TI  - Real-time PCR for rapid genotyping of angiotensin-converting enzyme
      insertion/deletion polymorphism.
AB  - OBJECTIVE: To develop a real-time PCR technique for detection of the
      insertion/deletion (I/D) polymorphism of angiotensin-converting enzyme (ACE)
      gene. DESIGN AND METHODS: Three primers were designed for performing real-time
      PCR in the presence of SYBR Green I as flurochrome followed by melting curve
      analysis. Forty human genomic DNA that have been genotyped by two-rounds of
      conventional PCR were used for evaluation of this technique. RESULTS: Melting
      curve analysis indicated the melting peak at 73.9 degrees C and 76.2 degrees C
      corresponding to the presence of I and D alleles, respectively. Comparable
      genotyping results were obtained by both conventional and real-time PCR. Besides,
      the mistyping of ID allele individuals by the first run of conventional PCR were
      accurately genotyped by single-tube real time PCR. CONCLUSIONS: The real-time PCR
      method presented in this study provides a rapid and sensitive way for genotyping
      of ACE gene that may be suitable for large-scale clinical and epidemiologic
      study.

PMID- 11849628
TI  - Age and gender dependent alterations in the activities of glutathione related
      enzymes in healthy subjects.
AB  - OBJECTIVES: Oxidative stress as a result of increased free radical production is
      implicated in the pathogenesis of several diseases. Specific antioxidant enzymes
      have a crucial role in the prevention of these deleterious effects. Since the
      activities of these enzymes differ significantly in different populations and
      seem to be affected by various environmental factors, in this study we aimed to
      determine the reference values of glutathione related antioxidant enzyme
      activities in the erythrocytes of healthy subjects and to investigate the
      possible variations as a function of age and gender in a healthy Turkish
      Mediterranean population. DESIGN AND METHODS: 130 healthy subjects (12-90 yr, 82
      females, 48 males) were divided into six different age groups. Erythrocyte
      glutathione peroxidase (GSH-PX), glutathione reductase (GR) and glutathione-s
      transferase (GST) activities were measured on a Hitachi 704 autoanalyser by the
      modification of previously described manual UV spectrophotometric methods.
      RESULTS: No significant differences were observed in erythrocyte GSH-PX, GR and
      GST activities between different age groups. Overall, GST activities were
      significantly higher in females compared with males (8.08 +/- 1.39, 6.88 +/- 1.51
      U/g Hb respectively, mean +/- SD, p < 0.001). A significant positive correlation
      between GSH-PX and GR activities was observed (r = 0.49, p < 0.001). CONCLUSION:
      The results of this study suggested that the activities of GSH-PX, GR and GST did
      not depend. GST activities overall were higher in females. The reference values
      that we obtained were different than the previous reports. This situation implies
      that each population should determine its own reference values and should
      investigate the influence of environmental factors and life style habits on the
      activities of these enzymes that constitute a major part of the antioxidant
      defense system in the human organism.

PMID- 11849629
TI  - The introduction of a transdermal hormonal contraceptive (Ortho Evra/Evra).

PMID- 11849630
TI  - Pharmacokinetic overview of Ortho Evra/Evra.
AB  - OBJECTIVE: The pharmacokinetics of norelgestromin, the primary active metabolite
      of norgestimate, plus ethinyl estradiol (EE), delivered by the once-weekly
      contraceptive patch (Ortho Evra/Evra), have been studied in eight trials. This
      overview summarizes the relevant pharmacokinetic data for the contraceptive
      patch. DESIGN: Review article. RESULT(S): The amount of norelgestromin and EE
      absorbed from the patch is proportional to patch size: the 20-cm(2) patch (Ortho
      Evra) delivers norelgestromin, 150 microg/d, and EE, 20 microg/d, to the systemic
      circulation. After single and multiple applications of the contraceptive patch,
      daily serum concentrations (area under the serum concentration-versus-time curve)
      of norelgestromin and EE were within the ranges generally seen with oral
      norgestimate, 250 microg/EE 35 microg (Ortho-Cyclen/Cilest), but without the
      peaks and troughs characteristic of oral dosing. Moreover, the contraceptive
      patch maintains serum concentrations of norelgestromin and EE within these ranges
      for up to 10 days, suggesting that clinical efficacy would be maintained even if
      a scheduled change is missed for as long as two full days. Regardless of the
      location of patch application (abdomen, buttock, upper outer arm, or torso
      [excluding breasts]) and even under conditions of heat, humidity, exercise, and
      cool-water immersion, efficacious concentrations of norelgestromin and EE are
      achieved. Coadministration of the patch with tetracycline did not affect the
      pharmacokinetics of norelgestromin and EE. CONCLUSION(S): The contraceptive patch
      exhibits an excellent pharmacokinetic profile, maintaining efficacious serum
      hormone concentrations under varying conditions.

PMID- 11849631
TI  - Contraceptive efficacy and cycle control with the Ortho Evra/Evra transdermal
      system: the analysis of pooled data.
AB  - OBJECTIVE: To present efficacy and cycle control data pooled from three pivotal
      studies of the contraceptive patch (Ortho Evra/Evra). DESIGN: Three multicenter,
      open-label, contraceptive studies that included up to 13 treatment cycles.
      SETTING: 183 centers. PATIENT(S): 3,319 women. INTERVENTION(S): Three consecutive
      7-day patches (21 days) with 1 patch-free week per cycle. MAIN OUTCOME
      MEASURE(S): Contraceptive efficacy and cycle control. RESULT(S): Overall and
      method failure life-table estimates of contraceptive failure through 13 cycles
      were 0.8% (95% CI, 0.3%-1.3%) and 0.6% (95% CI, 0.2%-0.9%), respectively.
      Corresponding Pearl indices were 0.88 (95% CI, 0.44-1.33) and 0.7 (95% CI, 0.31
      1.10). Contraceptive failure among women with a body weight < 90 kg (<198 lb) was
      low and uniformly distributed across the weight range. A subgroup of women with
      body weight > or = 90 kg (> or = 198 lb) may have increased risk of pregnancy.
      The incidence of breakthrough bleeding was low and decreased over time.
      CONCLUSION(S): In contraceptive patch users, the overall annual probability of
      pregnancy was 0.8% and the method failure probability was 0.6%. The efficacy of
      the patch was high and similar across age and racial groups. Among women < 90 kg
      (<198 lb), contraceptive failure was low and uniformly distributed across the
      range of body weights. In women > or = 90 kg (> or = 198 lb), contraceptive
      failures may be increased. Efficacy and cycle control have been shown to be
      comparable to an established oral contraceptive.

PMID- 11849632
TI  - A comparative and pooled analysis of the safety and tolerability of the
      contraceptive patch (Ortho Evra/Evra).
AB  - OBJECTIVE: To review the safety and tolerability of the contraceptive patch
      (Ortho Evra/Evra) versus a standard oral contraceptive (Triphasil) and to present
      the pooled safety and tolerability of the patch across three pivotal studies.
      DESIGN: Three open-label, contraceptive studies of up to 13 treatment cycles.
      SETTING: 183 centers. PATIENT(S): Comparative study (812 patch, 605 oral
      contraceptive); pooled analysis (3,330 patch). INTERVENTION(S): The patch regimen
      was three consecutive 7-day patches (21 days) followed by 1 patch-free week per
      cycle; the oral contraceptive was dosed according to the U.S. physician package
      insert. MAIN OUTCOME MEASURE(S): Adverse events, laboratory tests, vital signs,
      and body weight. RESULT(S): The incidence of most events was similar between the
      patch and oral contraceptive groups, with the exception of a higher incidence of
      application site reactions, breast discomfort (cycles 1 and 2 only), and
      dysmenorrhea in the patch group. Pooled analysis demonstrated that most
      application site reactions (92%) and breast symptoms (86%) were mild or moderate
      in severity, and <2% of participants discontinued the patch because of either
      event. Only 7 (0.2%) participants experienced a serious adverse event classified
      as possibly, probably, or likely related to the patch. The mean change in body
      weight from baseline to the end of treatment was an increase of 0.3 kg.
      CONCLUSION(S): Overall, the contraceptive patch is well tolerated and has a side
      effect profile similar to an established oral contraceptive.

PMID- 11849633
TI  - Assessment of compliance with a weekly contraceptive patch (Ortho Evra/Evra)
      among North American women.
AB  - OBJECTIVE: To determine compliance with the contraceptive patch (Ortho Evra/Evra)
      overall and by age among women in North America and to compare rates of perfect
      use with those of an established oral contraceptive. DESIGN: Data were pooled for
      three contraceptive studies in which women participated for up to 13 cycles; the
      subset of centers in North America was used in this analysis. SETTING: 76 North
      American centers. PATIENT(S): Healthy women 18-45 years of age. INTERVENTION(S):
      In all studies, the patch regimen was three consecutive 7-day patches (21 days)
      followed by 1 patch-free week per cycle. MAIN OUTCOME MEASURE(S): Perfect use for
      the patch or oral contraceptive, defined as 21 consecutive days of drug-taking
      followed by a 7-day drug-free period; for contraceptive patch users, no patch
      could be worn for more than 7 days. Oral contraceptives were used according to
      package labeling. RESULTS: For all contraceptive patch users in North America (n
      = 1,785), perfect use was consistent across age groups. The percentage of cycles
      with perfect use of the patch ranged within age groups from 88.1% to 91.0%. In
      the comparative study conducted only in North America, perfect use was also
      consistent across age groups for the patch (n = 812), but rates of perfect use
      for the oral contraceptive (n = 605) differed significantly by age.
      CONCLUSION(S): Age did not affect compliance with the patch among all North
      American women studied. In a comparative study of women at North American
      centers, compliance with the weekly contraceptive patch was significantly better
      than with an established oral contraceptive. The contraceptive patch is uniformly
      easy to use across all ages.

PMID- 11849634
TI  - Integrated summary of Ortho Evra/Evra contraceptive patch adhesion in varied
      climates and conditions.
AB  - OBJECTIVE: To assess the adhesive reliability of the contraceptive patch (Ortho
      Evra/Evra). DESIGN: Pooled data of 3,319 women from three contraceptive studies
      of up to 13 treatment cycles; a subset of 325 women of the pooled data from warm
      and humid climates; and 30 women from a three-period, crossover exercise study.
      SETTING: 184 centers. PATIENT(S): 3,349 healthy women. INTERVENTION(S): In the
      contraceptive studies, each treatment cycle consisted of three consecutive 7-day
      patches (21 days) followed by one patch-free week. During each treatment period
      in the exercise study, women wore the patch for 7 days and participated in one of
      six activities (normal activity, excluding bathing; sauna; whirlpool; treadmill;
      cool-water immersion; or a combination of activities) each day at a supervised
      health center. MAIN OUTCOME MEASURE(S): Patch adhesion. RESULT(S): In the
      contraceptive studies, 4.7% of patches were replaced because they fell off (1.8%
      [1,297 of 70,552 patches]) or became partly detached (2.9% [2,050 of 70,552
      patches]); patch replacement rates in centers from a warm, humid climate were
      1.7% (85 of 4,877 patches) and 2.6% (128 of 4,877 patches), respectively. Only
      one of 87 patches (1.1%) completely detached in the exercise study.
      CONCLUSION(S): The reliability of adhesion of the contraceptive patch is
      excellent and consistent across all studies; only 1.8% and 2.9% of patches
      required replacement due to complete or partial detachment, respectively. Heat,
      humidity, and exercise do not affect adhesion.

PMID- 11849635
TI  - Pterin transport and metabolism in Leishmania and related trypanosomatid
      parasites.
AB  - The folate metabolic pathway has been exploited successfully for the development
      of antimicrobial and antineoplasic agents. Inhibitors of this pathway, however,
      are not useful against Leishmania and other trypanosomatids. Work on the
      mechanism of methotrexate resistance in Leishmania has dramatically increased our
      understanding of folate and pterin metabolism in this organism. The metabolic and
      cellular functions of the reduced form of folates and pterins are beginning to be
      established and this work has led to several unexpected findings. Moreover, the
      currently ongoing sequencing efforts on trypanosomatid genomes are suggesting the
      presence of several gene products that are likely to require folates and pterins.
      A number of the properties of folate and pterin metabolism are unique suggesting
      that these pathways are valid and worthwhile targets for drug development.

PMID- 11849636
TI  - Transforming growth factor-beta and insulin-like signalling pathways in parasitic
      helminths.
AB  - The signal transduction pathways involved in regulating developmental arrest in
      the free-living nematode, Caenorhabditis elegans, are fairly well characterised.
      However, much less is known about how these processes may influence the
      developmental timing and maturation in helminth parasites. Here, we provide an
      overview of two signalling pathways implicated in the regulation of dauer larva
      formation in C. elegans, the insulin-like signalling pathway and the transforming
      growth factor-beta pathway, and explore what is known about these signalling
      pathways in a variety of parasitic helminths. Understanding the differences about
      how these pathways are affected by environmental cues in free-living versus
      parasitic species of helminths may provide insights into novel mechanisms for the
      control or prevention of helminth-induced disease.

PMID- 11849637
TI  - Activation of distinct signal transduction pathways in Trypanosoma cruzi isolates
      with differential capacity to invade host cells.
AB  - Mammalian cell invasion by Trypanosoma cruzi requires the activation of signal
      transduction pathways that result in a Ca(2+) response both in the parasite and
      the host cell. By using drugs that interfere with the signalling processes, we
      investigated if the difference in the ability of T. cruzi isolates to invade host
      cells was associated with the activation of distinct signalling routes in the
      parasites. Experiments were performed with metacyclic trypomastigotes, the
      developmental forms that initiate infection in the mammalian host, using the
      highly invasive isolate CL and the poorly infective isolate G, which belong to
      distinct phylogenetic lineages. Treatment of parasites with adenylyl cyclase
      activator forskolin increased the infectivity of the G but not of the CL isolate
      towards HeLa cells. On the other hand, a specific protein tyrosine kinase
      inhibitor genistein reduced by approximately 75% the penetration of CL but not of
      G isolate into HeLa cells. In the CL but not in the G isolate, protein tyrosine
      kinase mediated the phosphorylation of a 175kDa protein in a manner inducible by
      a HeLa cell extract. Upon treatment with the phospholipase C inhibitor U73122, or
      with drugs such as caffeine, which affects Ca(2+) release from inositol-1,4,5
      triphosphate-sensitive stores, or thapsigargin, an inhibitor of intracellular
      Ca(2+) transport ATPases, the infectivity of the CL but not of the G isolate
      diminished significantly (P<0.005). In both isolates, a combination of ionomycin
      plus NH(4)Cl or nigericin released Ca(2+) from acidic vacuoles containing a
      Ca(2+)/H(+) exchange system. This treatment reduced the infectivity of metacyclic
      forms of the G but not of the CL isolate. Taken together, these data suggest
      that, for host cell invasion, distinct signalling pathways are activated in
      metacyclic trypomastigotes of the two isolates, leading to Ca(2+) release from
      different intracellular compartments.

PMID- 11849638
TI  - Cloning and characterisation of mmc-1, a microfilarial-specific gene, from Brugia
      pahangi.
AB  - Nine differentially expressed genes were cloned from Brugia pahangi in a screen
      which sought to identify cDNAs that were differentially expressed between the
      microfilariae from the mammalian host and the mosquito vector. One gene (mmc-1),
      that was up-regulated in mammalian-derived microfilariae, was characterised in
      detail. RT-PCR analysis demonstrated that mmc-1 was specific to the microfilarial
      stage of the life cycle and was not transcribed by developing microfilariae in
      utero, but only following the release of the microfilariae from the adult female.
      Analysis of DNA from other filarial worms suggested that mmc-1 may be a Brugia
      specific gene. Using serum samples from individuals exposed to Brugia malayi
      infection, it was shown that MMC-1 was specifically recognised by antibodies of
      the IgG3 subclass. mmc-1 has no homologues in the data bases and its function in
      the parasite is unknown.

PMID- 11849639
TI  - VSP417-6, a variant-specific surface protein encoded at a sixth locus within the
      vsp417 gene subfamily of Giardia intestinalis.
AB  - A sixth locus (vsp417-6) belonging to the vsp417 gene subfamily, a subset of the
      family of genes that encodes 'variant-specific' surface proteins (VSP) in
      Giardia, is described. The sequence of vsp417-6(A-I), the ortholog representing
      the vsp417-6 locus in isolates of the type A-I (Assemblage A, Group I) genotype
      of Giardia intestinalis, was determined from a cloned 5.5-kb Hind III fragment of
      genomic DNA derived from isolate Ad-1/C1. The gene encodes a 704 residue
      polypeptide (VSP417-6(A-I), Mr 71,674) that has 75% identity (92% similarity)
      over a 718 residue overlap with the prototype of the VSP417 subfamily, VSP417-1(A
      I)-encoded by the vsp417-1 (syn. tsa417) locus in type A-I isolates. Alignment of
      VSP417-6(A-I) with the deduced sequences of other known members of this subfamily
      identified one polypeptide, encoded by a gene found in type A-II (Assemblage A,
      Group II) isolates, whose homology with VSP417-6(A-I) (91% identity, 98%
      similarity over 713-residues) indicated that it was VSP417-6(A-II), the VSP417-6
      ortholog in type A-II isolates. Sequence-based phylogenetic analyses of known
      VSP417 subfamily members defined several loci that predate the emergence of the A
      I and A-II sublineages of G. intestinalis. Related sequences that may correspond
      to additional, uncharacterised vsp417 subfamily genes were identified in genomic
      DNA by Southern hybridisation using subfamily- and locus-specific probes. Variant
      specific expression of vsp417-1 and vsp417-6 within axenic cultures of G.
      intestinalis was detected by in situ mRNA hybridization, indicating that these
      genes are functional and that they are expressed in an alternative fashion with
      other vsp genes in these organisms.

PMID- 11849640
TI  - Functional domains of the rDNA promoter display a differential recognition in
      Leishmania.
AB  - A construct containing the RNA polymerase I promoter of Leishmania (L.)
      amazonensis, driving the expression of cloramphenicol acetyl transferase reporter
      gene, was better recognised by heterologous hosts species Leishmania (L.) major
      and Leishmania (L.) mexicana than by the homologous host L. (L.) amazonensis. The
      rDNA promoter domains responsible for recognition were functionally mapped. The
      core domain (-74 to +170) conferred a barely equal recognition on homologous or
      heterologous cells, slightly favouring to the later. Addition of the upstream
      domain (-196 to -74) repressed the expression in all cells tested. The third
      domain, consisting of repeated elements (upstream to -196 in L. (L.)
      amazonensis), enhanced by about 20 times the core activity of homologous species
      and by about 40 times the heterologous ones. Gel mobility shift patterns
      generated by the binding of core sequence of L. (L.) amazonensis to nuclear
      extracts of the Leishmania species suggested that the rDNA transcriptional
      machinery is a complex DNA-protein association particular for each species. A
      model is proposed to explain the mechanism and possible interactions of
      transcription machinery in the regulation of rDNA expression in phylogenically
      related organisms.

PMID- 11849641
TI  - Developmentally regulated expression of a cell surface class I nuclease in
      Leishmania mexicana.
AB  - Leishmania mexicana, like other trypanosomatid parasites, is a purine auxotroph
      and must obtain these essential nutrients from its sandfly and mammalian hosts. A
      single copy gene encoding its unique externally oriented, surface membrane,
      purine salvage enzyme 3'-nucleotidase/nuclease, was isolated. Structural features
      of the deduced protein included: an endoplasmic reticulum-directed signal
      peptide, several conserved class I catalytic and metal co-factor (Zn(2+)) binding
      domains, transmembrane anchor sequence and a C-terminal cytoplasmic tail. 3'
      Nucleotidase/nuclease gene (mRNA) and protein (enzyme activity) expression were
      examined in three different L. mexicana developmental forms: procyclic
      promastigotes, metacyclic promastigotes and amastigotes. Results of both
      approaches demonstrated that the 3'-nucleotidase/nuclease was a stage-specific
      enzyme, being expressed by promastigote forms (stages restricted to the insect
      vector), but not by amastigotes (which produce disease in mammalian hosts).
      Starvation of these parasites for purines resulted in the significant up
      regulation of both 3'-nucleotidase/nuclease mRNA and enzyme activity in
      promastigotes, but not in amastigotes. These results underscore the critical role
      that the 3'-nucleotidase/nuclease must play in purine salvage during the rapid
      multiplicative expansion of the parasite population within its insect vector. To
      our knowledge, the L. mexicana 3'-nucleotidase/nuclease is the first example of a
      nutrient-induced and developmentally regulated enzyme in any parasitic protozoan.

PMID- 11849642
TI  - Adverse effects of praziquantel treatment of Schistosoma japonicum infection:
      involvement of host anaphylactic reactions induced by parasite antigen release.
AB  - The present study using a murine model heavily infected with Schistosoma
      japonicum aimed to elucidate the pathogenesis of adverse effects of praziquantel
      treatment of schistosome-infected subjects. Inbred BALB/c mice were infected with
      S. japonicum (Yamanashi strain) before being treated with a single dose of
      praziquantel at 4 or 8 weeks p.i. All the mice treated at 8 weeks p.i. exhibited
      signs typical of systemic anaphylaxis until half of them died shortly after
      praziquantel administration. At autopsy, these mice exhibited remarkable
      intestinal alterations characterised by increased mucosal permeability, mucosal
      oedema and petechial haemorrhage, which are changes typical of immediate
      intestinal anaphylaxis. In these mice treated at 8 weeks p.i., degranulation of
      intestinal mast cells was frequently observed, which was particularly remarkable
      around S. japonicum eggs hatched as an effect of praziquantel. Furthermore, the
      plasma histamine concentration just after praziquantel treatment was much higher
      in mice at 8 weeks p.i. than that in uninfected mice or in S. japonicum-infected
      mice without drug treatment. In contrast, none of these intestinal changes was
      observed in untreated or uninfected control mice, or in mice administered
      praziquantel at 4 weeks p.i., in which worm pairs had just reached sexual
      maturation and begun egg-laying. The finding by ELISA that serum IgM and IgA
      levels specific to S. japonicum eggs decreased immediately after praziquantel
      treatment, together with the results of immunohistochemistry, revealed the sudden
      release of parasite antigens from the eggs hatched by praziquantel treatment. The
      results of this study demonstrate that adverse effects of praziquantel treatment
      of schistosomiasis characterised by abdominal signs depend on anaphylactic
      reactions due to parasite antigens, especially antigens from eggs hatched as an
      effect of praziquantel.

PMID- 11849644
TI  - Detection of Sarcocystis neurona antibodies in French horses with neurological
      signs.

PMID- 11849647
TI  - Treating atherosclerosis: local drug delivery from laboratory studies to clinical
      trials.
AB  - Treating only the specific section of the vascular bed that is diseased appears
      to make sense. Giving drugs systematically to treat perhaps only a few
      centimetres of affected artery carries with it the risk of systemic side effects
      and reduced efficacy consequent on low concentrations of agent at the site of the
      problem. There has thus been great interest since the early 1990s in local drug
      delivery. Initial targets were the thrombotic response to plaque disruption but
      the problems arising from the incidental damage inflicted by devices used in
      interventional cardiology and the pathological consequences of this, namely
      smooth muscle cell initiated intimal hyperplasia, soon became the focus of pre
      clinical studies. Problems to be overcome were the low efficiency of delivery of
      drugs and the low retention rates. Solutions to these problems included the
      development of strategies to target drugs, through the use of antibodies directed
      at antigens newly released at the site of damage. As it became clear that stents
      were becoming central to the attainment of a better clinical response to
      intervention by their inherent physical properties, it also became obvious that
      stents could be used to deliver agents. Issues such as which stent, how to load
      the drug onto the stent and what drug to use to inhibit the unwanted
      pathobiological response are ongoing issues.

PMID- 11849643
TI  - Growth inhibition of bloodstream forms of Trypanosoma brucei by the iron chelator
      deferoxamine.
AB  - Treatment of bloodstream forms of Trypanosoma brucei with the iron chelator
      deferoxamine inhibits the proliferation of the parasites. Compared with mammalian
      cells, bloodstream forms of Trypanosoma brucei are 10 times more sensitive to
      iron depletion. The primary target of the chelator is obviously the intracellular
      iron as the toxicity of deferoxamine is abolished by addition of holotransferrin,
      the exogenous source of iron for the parasite. To identify probable target sites,
      the effect of deferoxamine on ribonucleotide reductase, alternative oxidase and
      superoxide dismutase, three iron-dependent enzymes in bloodstream-form
      trypanosomes, was studied. Incubation of the parasites with the chelator leads to
      inhibition of DNA synthesis and lowers oxygen consumption indicating that
      deferoxamine may affect ribonucleotide reductase and alternative oxidase. The
      compound does not inhibit the holoenzymes directly but probably acts by chelating
      cellular iron thus preventing its incorporation into the newly synthesised
      apoproteins. Treatment of the parasites with deferoxamine for 24 h has no effect
      on the activity of superoxide dismutase. The results have implications for
      antitrypanosomal drug development based on specific intervention with the
      parasite's iron metabolism.

PMID- 11849648
TI  - Differential expression of ribosomal L31, Zis, gas-5 and mitochondrial mRNAs
      following oxidant induction of proliferative vascular smooth muscle cell
      phenotypes.
AB  - Treatment of cultured vascular smooth muscle cells (vSMCs) with benzo(a)pyrene
      (BaP), a prooxidant present in the particulate phase of tobacco smoke, induces
      highly proliferative (i.e. atherogenic) phenotypes. Critical early target genes
      in vSMCs have been identified, but patterns of gene expression following repeated
      cycles of carcinogen treatment in vivo have yet to be evaluated. In the present
      study, male Sprague-Dawley rats (175-200 g) were given weekly injections of BaP
      (10 mg/kg) for 8 weeks to induce atherogenic phenotypes. At the end of this
      atherogenic regimen, vSMCs were established in serial culture and monitored for
      patterns of proliferative activity and gene expression. vSMCs isolated from BaP
      treated animals (hence forth referred to as BaP cells) exhibited constitutively
      increased growth rates, and marked enhancement of proliferation in response to
      serum mitogens. Differential display polymerase chain reaction (DD-PCR) and
      Northern blot analyses revealed that mRNAs for ribosomal protein L31 and Zis
      genes were suppressed, while gas-5 and mitochondrial mRNAs were overexpressed in
      BaP cells relative to control mRNA populations. In situ hybridization experiments
      in vascular tissue confirmed these alterations in vivo. This is the first report
      linking expression of these genes to proliferative dysregulation during the
      course of experimentally-induced atherogenesis.

PMID- 11849650
TI  - Clinicopathological significance of lipid peroxidation in carotid plaques.
AB  - Several reports have suggested an association between lipid peroxidation and
      human carotid atherosclerosis, but few reports have demonstrated a link between
      lipid peroxidation and carotid plaques in humans. In this study, we investigated
      the relationship between clinical features, histopathological characteristics and
      lipid peroxidation in patients undergoing carotid endarterectomy (CEA). Forty-one
      carotid plaques were obtained. A portion of the most severe lesions was subjected
      to histopathologic examination, and the remainder of the plaques examined for
      lipid peroxidation. Thiobarbituric acid-reactive substances (TBARS) values were
      determined as a marker for lipid peroxidation. The lipid-rich core (LC) and
      macrophage infiltration (Mphi) component as a percentage of total plaque area
      were measured morphometrically. Based on the results, all plaques were classified
      into four groups. Group I (GI): LC <10%; Group IIa (GIIa): LC 10-30%, Mphi <5%;
      Group IIb (GIIb): LC 10-30%, Mphi < or = 5%, and Group III (GIII): LC < or =30%.
      The plaque TBARS values of GIII were significantly higher than those of GI, GIIa,
      and GIIb. The TBARS values of GIIb were one-and-a-half times higher than those of
      GIIa. Our results show that lipid peroxidation in carotid plaques is
      significantly associated with carotid atherosclerosis, especially plaque
      instability. These findings provide direct evidence of an association between
      lipid peroxidation and human atherosclerosis.

PMID- 11849649
TI  - Oxidized low density lipoprotein-induced LFA-1-dependent adhesion and
      transendothelial migration of monocytes via the protein kinase C pathway.
AB  - Inflammatory and immune responses are highly relevant processes in the
      pathogenesis of atherosclerosis, as illustrated by the central event of monocyte
      accumulation in atherosclerotic plaques. Integrin LFA-1-mediated adhesion of
      circulating monocytes to the endothelium is a prerequisite for recruitment of
      monocytes to these areas. Integrin-mediated adhesion is tightly regulated and
      integrins are only functional in response to particular monocyte activation
      stimuli. We investigated the role of oxidized low-density lipoprotein (LDL) in
      adhesion of resting monocytes prepared by elutriation from endothelium. Our
      results showed that: (1) oxidized LDL (and MCP-1) induced both LFA-1-mediated
      adhesion of monocytes to endothelial cells and transendothelial migration of
      monocytes; (2) oxidized LDL functionally transformed monocyte LFA-1 to an
      activated form; (3) oxidized LDL induced F-actin polymerization and cytoskeletal
      rearrangement within seconds; and (4) the LDL-associated antioxidant, alpha
      tocopherol, but not beta-tocopherol, inhibited both F-actin polymerization and
      LFA-1-mediated adhesion of monocytes, which paralleled the effect of protein
      kinase C (PKC) inhibitors. Our results indicate that oxidized LDL plays a pivotal
      role in triggering LFA-1 activation and LFA-1-mediated adhesion and
      transmigration of monocytes to sites of atherosclerotic plaques, via the PKC
      pathway.

PMID- 11849651
TI  - Endothelin-1 and atherosclerosis: potential complications associated with
      endothelin-receptor blockade.
AB  - Atherosclerotic vascular disease remains the single most prevalent cause of death
      and morbidity in the western world. Endothelin-1 (ET-1) is a potent
      vasoconstrictor peptide that also possesses mitogenic activity on many cell
      types, including vascular smooth muscle cells. Raised plasma and tissue levels of
      ET-1 have been described in atherosclerosis in animal models and in man,
      suggesting that this peptide plays a pathophysiological role in this condition.
      Two main ET-1 receptors have been cloned (ET(A) and ET(B)). Mixed ET(A/B) and
      receptor subtype selective antagonists are now available. Since ET-1 is generally
      believed to be a 'pathophysiological peptide', we discuss the therapeutic
      potential of ET-1 antagonists in atherosclerosis and consider whether, at certain
      sites in this process, ET-1 may play a beneficial role. In such situations ET
      antagonism may be undesirable.

PMID- 11849652
TI  - Involvement of ICAM-1 in the progression of atherosclerosis in APOE-knockout
      mice.
AB  - Recent clinical evidence has indicated that the level of soluble ICAM-1 (sICAM-1)
      is correlated with the severity of atherosclerosis and can predict future
      cardiovascular events. Here, using apolipoprotein E (APOE)-deficient mice, we
      investigated the level of sICAM-1 in parallel with endothelial ICAM-1 expression
      and aortic atherosclerosis. We also examined the effect of ICAM-1 deficiency
      during the progression of atherosclerosis using double knockout mice. The level
      of sICAM-1 increased significantly in parallel with the progression of
      atherosclerosis in APOE-deficient mice, while the sICAM-1 level remained constant
      in wild-type mice from 3 to 10 months of age. ICAM-1 staining was detected in
      virtually all endothelial cells, however, ICAM-1 was expressed strongly in the
      endothelium overlying atheromatous palque in APOE-deficient mice. Deficiency of
      ICAM-1 in APOE-deficient mice significantly reduced lesions after 5 and 10
      months. The present study supported the notion that the level of sICAM-1 is
      closely related with the severity of atherosclerosis and cardiovascular events,
      and also suggested that inhibition of ICAM-1 can delay the progression of
      atherosclerosis.

PMID- 11849653
TI  - Gonadal effects on plasma ACE activity in mice.
AB  - Angiotensin-converting enzyme (ACE) regulates blood pressure and is an important
      target in the management of hypertension. Hypertension is a gender biased
      disease. Plasma ACE activity is significantly higher in male mice (309 U/l) than
      female mice (237 U/l) and is reduced significantly upon gonadectomy to 224 and
      209 U/l, respectively. Although, the gonads influence plasma ACE activity in both
      male and female mice, the effect is more pronounced in male mice. Plasma ACE is
      derived from the cleavage of tissue ACE and lung has the highest concentration of
      tissue ACE. However, lung ACE activity is not gender dimorphic but increases
      significantly upon gonadectomy in both male and female. ACE mRNA level in the
      lung is not influenced by gender or gondaectomy. Therefore, the gonads affect
      plasma ACE activity by influencing cleavage of tissue ACE to plasma ACE and/or
      decrease stability of plasma ACE in gonadectomized mice is mediated.

PMID- 11849654
TI  - Visceral obesity and hyperinsulinemia modulate the impact of the microsomal
      triglyceride transfer protein -493G/T polymorphism on plasma lipoprotein levels
      in men.
AB  - The dyslipidemic state of visceral obesity is characterized by increased plasma
      triglyceride levels, low high-density lipoprotein-cholesterol concentration and
      alterations in low-density lipoprotein (LDL) composition and concentration. A
      functional, non-coding microsomal triglyceride transfer protein (MTP) -493G/T
      polymorphism of the microsomal triglyceride transfer protein gene has been
      related to variations in LDL-cholesterol levels. To study the effect of the MTP 
      493G/T polymorphism on lipoprotein levels in visceral obesity and
      hyperinsulinemia, a total of 227 men were assigned into two groups on the basis
      of their MTP -493G/T polymorphism, including 121 GG homozygotes and 105 carriers
      of the T allele (92 GT and 13 TT). The two genotypic groups did not differ for
      their physiological characteristics nor for lipoprotein--lipid profiles, before
      and after adjustment for age. However, GG homozygotes were characterized by
      higher fasting insulin levels than carriers of the T allele (P<0.05). When the
      two genotypic groups were further divided on the basis of their visceral adipose
      tissue (AT) accumulation, assessed by computed tomography, we observed that T
      allele carriers with low levels of visceral AT (<130 cm(2)) had decreased plasma
      total cholesterol and LDL-apolipoprotein B (LDL-apoB) levels compared to
      viscerally obese men (P=0.035 and P=0.0001, respectively). Among GG homozygotes,
      no significant difference were observed. Although not significant, T allele
      carriers characterized by visceral obesity tended to have smaller, denser LDL
      particles than T allele carriers characterized by a low accumulation of visceral
      AT. When subjects were divided on the basis of their fasting insulin levels, it
      appears that hyperinsulinemic men were characterized by a deteriorated
      lipoprotein--lipid profile when they were carriers of the T allele compared to
      normoinsulinemic men. In summary, visceral obesity and hyperinsulinemia modulate
      the impact of the MTP -493G/T polymorphism on plasma total cholesterol and LDL
      apoB levels, as well as on LDL peak particle diameter.

PMID- 11849655
TI  - Matrix metalloproteinases and tissue inhibitors of metalloproteinases in hamster
      aortic atherosclerosis: correlation with in-situ zymography.
AB  - Atherogenesis requires extracellular matrix (ECM) alterations, a process possibly
      mediated by matrix-degrading metalloproteinases (MMPs) and their endogenous
      tissue inhibitors (TIMPs). The objective of this study was to examine the
      immunohistochemical expression patterns of MMPs-1, -2, -3 and -9 and their tissue
      inhibitors, TIMPs-1, -2, -3 and -4 during the three major stages of
      atherosclerotic lesion development in hypercholesterolemic Syrian Golden
      hamsters. Aortic atherosclerotic lesions (fatty streak, fibro-fatty and advanced)
      were histologically characterized in treated hamsters at 12, 24, and 49 weeks.
      The immunochemistry expression of these MMPs and TIMPs were examined in treated
      aortic sections with lesions and control aortic sections without lesions. MMP
      activity in control aortas and atherosclerotic lesions was characterized by in
      situ zymography. Positive immunoreactivity for MMPs-2, -3, -9 and TIMPs-1, -2,-3,
      and -4 was observed in both control and atherosclerotic aortic arch segments,
      while MMP-1 was only observed in atherosclerotic lesions. Using in-situ
      zymography, we identified casein and gelatin degradation in fatty streak, fibro
      fatty and advanced lesions. The immunohistochemical expression of these MMPs and
      TIMPs were examined in treated aortic sections with lesions and control aortic
      sections without lesions. In all lesion stages, substrate degradation was
      inhibited with 1,10-phenanthroline. Degradation of these substrates was not
      observed in control aortas. In addition, substrate degradation was inhibited with
      1,10-phenanthroline. These findings suggested that in control segments, the net
      proteolytic balance was shifted in favor of MMP inhibition. Alternatively,
      despite the colocalization of MMPs and TIMPs in the treated segments, net
      proteolytic balance favored the catalytic MMPs.

PMID- 11849656
TI  - Influence of angiotensinogen M253T gene polymorphism and an angiotensin
      converting enzyme inhibitor on restenosis after percutaneous coronary
      intervention.
AB  - We studied the relation between renin-angiotensin system (RAS) related gene
      polymorphisms, such as angiotensin converting enzyme (ACE) insertion/deletion
      (I/D), angiotensinogen (AGT) M253T and angiotensin II type 1 receptor (AT1R)
      A1166C, and the effect of quinapril, an ACE inhibitor with high tissue-binding
      affinity, on preventing restenosis after percutaneous coronary intervention
      (PCI). A total of 253 patients successfully treated for coronary artery disease
      were randomly assigned to quinapril or control. Of the 215 patients who completed
      the follow-up, we determined gene polymorphisms in 204 patients with 241 lesions
      who provided blood samples for genotype determination. In the control, the ACE D
      homozygotes showed a smaller minimal lumen diameter (MLD) at follow-up (P=0.063).
      The other two genotypes of AGT and AT1R did not affect restenosis after PCI.
      According to quinapril treatment, the AGT T homozygotes significantly showed a
      beneficial effect of quinapril on MLD (P=0.013) and late lumen loss (P=0.013).
      The ACE I homozygotes also exhibited beneficial effects of quinapril on larger
      MLD (P=0.065). The AT1R genotype did not influence the quinapril effect. In
      conclusion, the AGT T homozygotes might benefit from effects of quinapril on
      preventing restenosis after PCI.

PMID- 11849657
TI  - Vasorelaxant properties of isolated human radial arteries: comparison with
      internal mammary arteries.
AB  - Radial arteries, used in revascularisation surgery, are prone to spasm. We have
      examined the ability of nitrovasodilators, calcium channel blockers, and K(ATP)
      channel openers to cause vasodilation, and to attenuate contractions due to
      depolarisation and receptor activation in radial and mammary arteries used in
      coronary artery bypass graft surgery. Two to three millimetre rings of artery
      obtained from patients at surgery were studied in organ baths in vitro.
      Constriction to KC1 and phenylephrine was examined before and again after
      treatment of the rings with drug or vehicle. Calcium channel blockers were the
      only compounds to inhibit contractions to both KC1 and phenylephrine. Sodium
      nitroprusside attenuated constriction to phenylephrine but not KC1 in both
      vessels. K(ATP) channel openers similarly attenuated constriction to
      phenylephrine in radial arteries but were much less effective in mammary
      arteries. These studies support the continued use of calcium blockers after
      revascularisation with radial artery but suggest that other classes of drug may
      be as effective at minimising spasm due to receptor mediated constriction.

PMID- 11849658
TI  - Microsomal triglyceride transfer protein: does insulin resistance play a role in
      the regulation of chylomicron assembly?
AB  - We have previously demonstrated that diabetes is associated with an increase in
      intestinal microsomal triglyceride transfer protein (MTP) mRNA in both the rat
      and rabbit models. The present study was designed to investigate the relationship
      between MTP expression and chylomicron assembly in an insulin resistant non
      diabetic animal model. Ten insulin resistant Zucker obese fa/fa rats and ten lean
      fa/minus sign rats were examined at 8-10 weeks of age. The lymph duct was
      cannulated and lymph collected for 4 h. Lymph chylomicrons were isolated by
      ultracentrifugation and their composition determined. RNA was extracted from
      intestinal mucosa and from the liver. MTP mRNA was measured using the RNase
      protection assay. Blood sugar in the fatty rats was significantly higher (6.3 +/
      1.2 vs. 5.4 +/-0.4 P<0.05) and plasma insulin was almost six times that of the
      lean rats (P<0.001). Plasma cholesterol and phospholipid but not triglyceride
      were significantly increased in the obese animals (P<0.01). Obese animals
      secreted significantly more lymph chylomicron apo B48 (0.05 +/-0.02 vs. 0.02 +/
      0.01 mg/h P<0.005), triglyceride (9.7 +/-5.3 vs. 3.8+/-1.9 mg/h P<0.005) and
      phospholipid (1.5 +/-0.7 vs. 0.4 +/-0.3 mg/h P<0.001). The only difference in the
      chylomicron particle composition between the two groups was a significant
      increase in phospholipid (P<0.01). Intestinal MTP mRNA expression was
      significantly higher in the fatty compared to the lean rats (22.1 +/-9.5 vs.
      7.8+/-5.6 amol MTP mRNA/microg total RNA P<0.001) as was hepatic MTP mRNA
      expression (6.9 +/-3.5 vs. 3.4 +/-1.5 amol MTP mRNA/microg total RNA, P<0.01).
      Thus in this animal model of insulin resistance, increased MTP, which was
      associated with increased chylomicron particle number, may play a crucial role in
      the development of atherosclerosis.

PMID- 11849659
TI  - Influence of LDL receptor gene mutation and apo E polymorphism on lipoprotein
      response to simvastatin treatment among adolescents with heterozygous familial
      hypercholesterolemia.
AB  - The efficacy of the inhibitors of HMG CoA reductase shows considerable
      interindividual variation and intense research has focused in the recent years to
      identify the genetic loci and environmental factors responsible for this
      variability. A randomized, double-blind, placebo-controlled clinical trial with
      simvastatin, an HMG CoA reductase inhibitor, was conducted in 63 adolescents (47
      treated versus 17 controls) with heterozygous FH. The patients were grouped
      according to known low-density lipoprotein (LDL) receptor gene mutation class.
      After 6 weeks of treatment with 20 mg/d of simvastatin, the mean reduction in
      plasma LDL-cholesterol in patients with a receptor-negative mutation (n=33) was
      39% whereas, in the receptor-defective mutation group (n=14), it was 31%
      (P=0.01). Multiple regression analyses showed that there was a significant
      association between the apo E polymorphism and LDL-cholesterol response to
      simvastatin only among heterozygotes for a receptor-negative mutation. In
      subjects carrying a receptor-defective mutation, however, we observed that 51% of
      the variability in LDL-cholesterol response was explained by variations in the
      dosage of simvastatin expressed in mg/kg/day (P=0.0028). There was no significant
      association between LDL-cholesterol response and the dosage of simvastatin among
      heterozygotes for a receptor-negative mutation. The results of the present study
      have shown that the contribution of apo E polymorphism and the dosage of
      simvastatin to the LDL-cholesterol responsiveness is influenced by the nature of
      the LDL receptor gene mutation.

PMID- 11849660
TI  - Lipid-lowering therapy with fluvastatin inhibits oxidative modification of low
      density lipoprotein and improves vascular endothelial function in
      hypercholesterolemic patients.
AB  - This prospective randomized trial was designed to elucidate clinically the effect
      of fluvastatin on inhibiting oxidation of the low density lipoprotein (LDL) and
      improving the vascular endothelial function as well as its lipid-lowering
      effects, in comparison with pravastatin. Of 64 consecutive dyslipidemic patients,
      40 patients, whose level of total cholesterol or LDL-cholesterol maintained the
      criteria of the hypercholesterolemia in spite of 12-week dietary therapy, were
      randomly assigned to receive either fluvastatin (n=20) or pravastatin (n=20). We
      assessed the titer of antibody against oxidized LDL (anti-Ox-LDL) as a biomarker
      for LDL-oxidation, and the forearm blood flow response during reactive hyperemia
      by venous occlusion plethysmography, which indicates the endothelium-dependent
      vasodilator capacity. After the 16-week lipid-lowering therapy, the anti-Ox-LDL
      titer significantly decreased in the fluvastatin group (P<0.01) but did not
      change in the pravastatin group. The percent increase in the forearm blood flow
      at the peak reactive hyperemia from the baseline value (%RH) significantly
      increased in the fluvastatin group (P<0.001) but did not change in the
      pravastatin group. The ratio of the %RH after the therapy over the baseline value
      negatively correlated with that of the anti-Ox-LDL titer (R=0.73, P<0.001) in all
      patients. Fluvastatin may serve as an ideal drug for reducing the risk of
      atherosclerosis, not only by its cholesterol-lowering effect but also by its
      unique effects of inhibiting LDL oxidation and improving the vascular endothelial
      function.

PMID- 11849661
TI  - Plasma free fatty acid levels and the risk of ischemic heart disease in men:
      prospective results from the Quebec Cardiovascular Study.
AB  - Insulin resistance, through numerous related disturbances in glucose and
      lipoprotein-lipid metabolism, is associated with an increased risk of ischemic
      heart disease (IHD). The purpose of the present study was to examine the
      relationship between increased plasma free fatty acid (FFA) concentrations, as a
      feature of the insulin resistance syndrome, and the risk of IHD in men. Analyses
      were carried out in a nested, case-control sample of men selected from a
      population of 2103 individuals without IHD at baseline among whom 114 developed
      IHD during a 5-year follow-up period. Incident IHD cases were matched with
      controls for age, body mass index, smoking habits and alcohol intake. Analyses
      were performed while excluding (88 cases and 98 controls) and including (103
      cases and 99 controls) patients with type 2 diabetes. Among non-diabetic
      individuals, elevated plasma FFA concentrations (3rd tertile of the distribution)
      yielded a twofold increase in the risk of IHD (odds ratio [OR] 2.1, P=0.05)
      compared with lower plasma FFA levels (lowest tertile) after adjusting for non
      lipid risk factors. Further adjustment for insulin, triglycerides, apolipoprotein
      B, HDL cholesterol and small dense LDL attenuated significantly the relationship
      between plasma FFA concentrations and the risk of IHD. High plasma FFA levels
      showed no synergism with selected features of the insulin resistance syndrome in
      determining the risk of IHD. Inclusion of diabetic subjects in the study did not
      improve FFA independent prognostic value to the risk of IHD. These results
      suggest that elevated plasma FFA concentrations are associated with an increased
      risk of IHD. However, a single fasting measurement of plasma FFA levels does not
      appear to improve our ability to predict IHD onset in men when information on
      other risk factors is considered.

PMID- 11849662
TI  - Elevated plasma activator inhibitor 1 is not related to insulin resistance and to
      gene polymorphism in healthy centenarians.
AB  - Previous studies demonstrated a relationship between the degree of insulin
      resistance and plasma plasminogen activator inhibitor type-1 (PAI-1) levels. We
      aim at investigating the relationship between the degree of insulin resistance
      and plasma PAI-1 levels in aged subjects (n=83) and in healthy centenarians
      (n=42). In all subjects the degree of insulin resistance was assessed by HOMA
      method. Our data demonstrated that healthy centenarians have higher plasma PAI-1
      levels (73.1+/-13.9 vs 23.7+/-14.7 ng/ml, P<0.001) and lower degree of insulin
      resistance (1.4+/-0.5 vs 3.3+/-1.3, P<0.001) than aged subjects. In aged subjects
      plasma PAI-1 levels correlated with the degree of insulin resistance (r=0.61,
      P<0.001), fasting plasma triglycerides (r=0.74, P<0.001) and age (r=0.33,
      P<0.001). All such associations were lost in centenarians. Plasma PAI-1 Ag levels
      were also similar in aged subjects and centenarians even after categorization for
      PAI gene polymorphism. In multivariate analysis, a model made by age, sex, body
      mass index, fasting plasma triglycerides, HOMA and PAI-1 gene explained 65 and
      50% of plasma PAI-1 level variations in aged subjects and centenarians,
      respectively. Nevertheless, HOMA (P<0.001) was significantly and independently
      associated with plasma PAI-1 levels only in aged subjects. In conclusion, our
      data demonstrates that in healthy centenarians, plasma PAI-1 were not associated
      with the degree of insulin resistance as in aged subjects. Frequency of PAI-1
      genotype does not provide an explanation for such differences between aged
      subjects and centenarians.

PMID- 11849663
TI  - Positive family history for coronary heart disease and 'midband lipoproteins' are
      potential risk factors of carotid atherosclerosis in familial
      hypercholesterolemia.
AB  - Patients with heterozygous familial hypercholesterolemia (FH) were examined with
      B-mode ultrasound in order to determine intima-media thickness (IMT) in the
      common carotid artery, and to uncover potential risk factors responsible for the
      development of IMT. Ninety seven FH subjects and 132 non FH type IIa
      hyperlipidemic subjects were involved in the present study. Age was found to
      correlate positively with IMT in both FH and non FH groups. FH individuals showed
      a higher IMT, along with elevated low density lipoprotein (LDL) cholesterol
      levels, compared with age-matched non FH individuals. To clarify potential
      factors contributing to the formation and development of carotid atherosclerosis,
      we divided the FH subjects into two subgroups, namely FH with high IMT group
      (HIG), and those with low IMT group (LIG). We investigated those two subgroups on
      the presence of angiographically documented coronary heart disease (CHD), of
      family history of CHD and of 'midband lipoproteins' by polyacrylamide gel
      electrophoresis (PAGE) analysis, by matching for age and LDL-cholesterol (LDL-C)
      level. Fifty percent of FH men in HIG was found to have CHD, whereas only 14% of
      those in LIG had CHD (P<0.05). Thirty-three percent of FH women in HIG was found
      to have CHD, whereas only 12% of those in LIG had CHD (P<0.05). Fifty percent of
      FH men in HIG was found to have 'midband lipoproteins', whereas only 7% of those
      in LIG had 'midband lipoproteins' (P<0.01). Seventy-three percent of FH women in
      HIG had 'midband lipoproteins', whereas only 21% of those in LIG had 'midband
      lipoproteins' (P<0.0005). Fifty-five percent of FH men in HIG was had positive
      family history for CHD, whereas only 14% of those in LIG had positive family
      history for CHD (P<0.05). Sixty-three percent of FH women in HIG was found to
      have positive family history for CHD, whereas only 29% of those in LIG had
      positive family history for CHD (P<0.05). Based on these findings, we propose
      that, besides age and elevated levels of LDL-C, positive family history for CHD
      and 'midband lipoproteins' are important determinants for the development of
      carotid atherosclerosis in FH individuals in Japanese population.

PMID- 11849664
TI  - HDL particle size: a marker of the gender difference in the metabolic risk
      profile.
AB  - A low plasma HDL-cholesterol concentration is an important risk factor for
      coronary heart disease (CHD) and is often accompanied by increased triglyceride
      concentrations. Women have generally higher HDL-cholesterol and lower
      triglyceride concentrations and concomitantly are at lower risk of CHD than men.
      As HDL particle size is a new and potentially important marker of CHD risk, we
      have examined the potential gender difference in HDL particle size, assessed by
      nondenaturing 4-30% polyacrylamide gradient gel electrophoresis, in a sample of
      men (n=231) and women (n=183). Overall, men were characterized by a less
      favorable lipoprotein--lipid profile, which was accompanied by smaller HDL
      particle size compared to women. However, when men and women were matched for HDL
      particle size and compared for their metabolic profile, it was found that both
      genders were characterized by similar plasma lipoprotein--lipid profile despite
      the fact that women were characterized by higher levels of total body fat but
      lower waist girth than men. In summary, HDL particle size is a strong marker of
      the gender-related difference in the determination of the metabolic risk profile.

PMID- 11849665
TI  - Subclinical atherosclerosis in multiple vascular beds: an index of
      atherosclerotic burden evaluated in postmenopausal women.
AB  - The Healthy Women Study has evaluated risk factor changes as women go through the
      menopause. In 274 women, measures of atherosclerosis in the coronary, aorta and
      carotid arteries were obtained at 8 years postmenopause using electron beam
      tomography and carotid ultrasound. The purpose of this study was to evaluate the
      association between baseline premenopausal risk factors and subclinical disease
      in various vascular beds and with an aggregate atherosclerosis index based on all
      subclinical measures. The prevalence of measurable disease for the coronaries,
      carotids and aorta was 45, 55 and 72%, respectively. Disease measures across
      these three locations were significantly correlated (P<0.001). Premenopausal LDL,
      triglycerides, blood pressure (BP) and smoking were associated with each measure
      of subclinical atherosclerosis, and were strikingly associated with the number of
      elevated disease measures. Among 126 women taking hormone replacement therapy
      (HRT), there was a strong positive association between systolic BP and
      subclinical atherosclerosis (P<0.001). No such relationship was seen among women
      not on HRT and this interaction was significant (P=0.048). An index of
      subclinical atherosclerosis rather than measurement at a single arterial site may
      be the best estimate of disease risk. Such a measure should be evaluated for its
      prognostic value along with individual measures of subclinical disease. Women
      with lower premenopausal risk factors did not develop high levels of subclinical
      atherosclerosis, suggesting that atherosclerosis is a preventable disease in
      women.

PMID- 11849666
TI  - Recognition of familial dyslipidemias in 5-year-old children using the lipid
      phenotypes of parents. The STRIP project.
AB  - Adult dyslipidemias may reveal familial and, therefore, offspring dyslipidemias.
      We evaluated the prevalences of the adult-offspring dyslipidemias in 441 general
      population families composed of both parents and one 5-year-old child. Family
      members were classified using the 90th or 10th percentiles for
      hypercholesterolemia (IIA), hypertriglyceridemia (IV), combined hyperlipidemia
      (IIB), and low high density lipoprotein cholesterol concentration without
      hyperlipidemia (hypoHDL). In familial combined hyperlipidemia (FCHL), the IIB
      phenotype was in one generation and one of the three hyperlipidemias in the other
      generation. Finally, the parental dyslipidemia phenotypes and elevated lipids
      (>80th percentile) that reveal offspring dyslipidemia were selected by stepwise
      logistic regression. Either the IIA-, IV- or hypoHDL phenotype was found in both
      generations in 2.8, 2.0 and 1.4% of the families, respectively. FCHL was seen in
      1.8% of the families, which confirms the earlier views. The predictive values of
      the elevated parental cholesterol, type IV or hypoHDL parents to find type IIA,
      IV and hypoHDL children were low for systematic screening: 16, 13 and 15%,
      respectively. However, 44% of the children of IIB parents expressed
      hyperlipidemia (odds ratio 4.7, P=0.006). The IIB phenotype of the parent is a
      good predictor of the child's hyperlipidemia, and when encountered, it indicates
      that the lipids of the child should be studied. This would be as important as
      selective screening of familial hypercholesterolemia.

PMID- 11849667
TI  - Dietary determinants of serum paraoxonase activity in healthy humans.
AB  - The associations between habitual diet and a variety of markers of lipid
      peroxidation or oxidative stress in a group of 95 healthy comparatively young
      Finnish volunteers (24 male and 71 females) were investigated. The habitual diet
      of the subjects was evaluated with a 3-day food record. The following biochemical
      parameters related to lipid peroxidation or oxidative stress were measured:
      lagtime of Cu2+ induced LDL oxidation in vitro, lipid hydroperoxides and Schiff
      bases produced during the LDL oxidation test, malondialdehyde measured as
      thiobarbituric acid-reactive substances from native LDL and Cu2+ oxidized LDL,
      serum paraoxonase (PON) activity. Serum PON activity showed most constantly
      associations with habitual diet. PON activity correlated negatively (r=-0.31 to 
      0.37) with intake of vegetables, total and water-soluble fiber, as well as intake
      of beta-carotene. Highly significant difference (P=0.005) in PON activity between
      lowest (<135 g/day) and highest (>256 g/day) vegetable intake quartiles was
      found. Malondialdehyde levels showed conflicting associations with diet. The
      results suggest that the significantly lower PON activity associated with high
      vegetable intake needs to be studied further.

PMID- 11849668
TI  - C-reactive protein predicts death in patients with previous premature myocardial
      infarction--a 10 year follow-up study.
AB  - Atherosclerosis is an inflammatory disease. C-reactive protein (CRP), a marker of
      inflammation, is associated with coronary heart disease (CHD). We measured CRP in
      a cohort of 247 patients (193 males and 54 females) who had had their first
      myocardial infarction (MI) at age < or = 55 (males) or < or = 60 (females). The
      cut-off values of the 25th, 50th and 75th centiles of CRP were 1.20, 2.37 and
      4.20 mg/l. After 10 years, a total of 44 patients (17.8%) had died, 36 (81.8%) of
      cardiac causes. Unadjusted and adjusted (i.e. for age, ejection fraction (EF),
      serum total cholesterol (TC), fibrinogen, smoking and hypertension) relative
      risks (RRs) for total and cardiac mortality were generated. CRP was a strong
      predictor of death of all causes due to its strength as predictor of cardiac
      death. The RR of cardiac death was doubled with increasing CRP quartiles, and
      patients in the top quartile had six times as high risk of cardiac death as
      patients in the lowest quartile. The RRs were moderately attenuated after
      adjustment, but still significant. We conclude that CRP is a strong predictor of
      mortality in patients with premature MI. Thus, inflammation appears to be a
      critical prognostic factor in patients with previous premature MI.

PMID- 11849669
TI  - Early inflammatory-immunological lesions in juvenile atherosclerosis from the
      Pathobiological Determinants of Atherosclerosis in Youth (PDAY)-study.
AB  - The Pathobiological Determinants of Atherosclerosis in Youth (PDAY)-study gave
      insight into the correlation between the classical risk factors for
      atherosclerosis development, such as hypercholesterolemia, hyperglycemia, high
      blood pressure and smoking in young Americans. We now present immunohistochemical
      data showing that immunological-inflammatory signs represent the first step
      towards atherosclerosis development in the arteries of young adults. In previous
      publications, we coined the term 'vascular-associated lymphoid tissue' (VALT) for
      the accumulation of mononuclear cells at regions of the arterial wall in healthy
      children and adolescents that are predisposed to the development of
      atherosclerotic lesions later in life if risk factors are present. In the present
      communication, we intended to close the gap between data from atherosclerotic
      arteries and those of healthy young children studied previously by our group. The
      PDAY-study comprising 15-34-year-old Americans who had no clinical symptoms of
      cardiovascular diseases offered a good basis for our intention. We document that
      inflammatory activity was found in all specimens, represented by activated T
      lymphocytes, dendritic cells, macrophages and aberrant MHC class II expression in
      the intima. We therefore demonstrated that immunological-inflammatory cells are
      present in the earliest stages of atherogenesis in 15-34-year-old subjects,
      arguing in favour of an initiating role of the immune system in atherosclerosis
      development.

PMID- 11849670
TI  - Gilbert syndrome and ischemic heart disease: a protective effect of elevated
      bilirubin levels.
AB  - BACKGROUND: Oxidation processes play an important role in atherogenesis.
      Bilirubin IXalpha is recognised as a potent antioxidant. In the present study, we
      assessed the role of elevated serum bilirubin levels in the prevention of
      ischemic heart disease (IHD). METHODS: The occurrence of IHD was determined in
      Gilbert syndrome (GS) patients above 40 years (n=50). The diagnosis was based on
      past medical history and ECG criteria. The occurrence was related to that of the
      comparable general population (n=2296). Serum biochemistry, including the total
      antioxidant status was evaluated in the GS subjects, IHD patients (n=38) and
      control subjects (n=38). RESULTS: The prevalence of IHD in GS subjects (aged
      49.7+/-9.0 years) was 2% (0.05-10.7%, 95% confidence interval), compared to 12.1%
      in a general population (P<0.05). Bilirubin, total antioxidant capacity and high
      density lipoprotein (HDL) cholesterol were found to be significantly higher in GS
      subjects compared to control groups (P<0.05). According to linear discriminant
      analysis, hyperbilirubinemia rather than elevation of HDL cholesterol levels
      seemed to be more important in protection from IHD. CONCLUSIONS: In the present
      study, low prevalence of IHD in GS subjects was detected. It may be presumed that
      chronic hyperbilirubinemia prevent the development of IHD by increasing the serum
      antioxidant capacity.

PMID- 11849671
TI  - Parameters of inflammation and infection in a community based case-control study
      of coronary heart disease.
AB  - BACKGROUND: increased levels of systemic inflammatory markers appear to be
      related to coronary heart disease (CHD) both in asymptomatic individuals and in
      subjects with established CHD. Whether these associations are related to
      confounding coronary risk factors or are explicable through chronic infectious
      conditions is not clear. OBJECTIVES: (1) to determine whether subjects with
      stable CHD differ from normal controls in inflammatory markers (CRP, SAA and
      fibrinogen) and/or in serostatus of four infectious agents (Helicobacter pylori,
      Chlamydia pneumoniae, CMV and EBV), independent of classical coronary risk
      factors. (2) To determine whether these inflammatory markers are related to the
      serostatus against these four infectious agents either in patients with CHD or in
      normal subjects. METHODS: in a large epidemiologic survey, 446 out of 16307 men
      at work, aged 35-59 years, had antecedents of myocardial infarction, CABG or PTCA
      or had prominent Q/QS waves on their resting ECG. They were compared with double
      the number (n=892) of men, matched for age, educational level and industry.
      Inflammatory biomarkers (CRP, fibrinogen and SAA) and antibodies against H.
      pylori, C. pneumoniae, CMV and EBV were measured, besides classical coronary risk
      factors. RESULTS: in univariate analyses, cases had higher CRP, fibrinogen and
      SAA levels than controls, but no differences were observed in serumantibody
      levels to any of the infectious agents. Markers of previous infections were not
      related to inflammatory biomarkers. In multivariate analyses CRP was
      significantly different between cases and controls independent of differences in
      other coronary risk factors and in the use of lipid lowering drugs and
      antiplatelet aggregants. CONCLUSIONS: in men at work with CHD, CRP levels are
      significantly different from controls, independent of known risk factors. No
      association was found between inflammatory biomarkers and positive serostatus
      against four infectious agents, neither in the patients nor in the healthy
      controls.

PMID- 11849673
TI  - Discriminative value of serum amyloid A and other acute-phase proteins for
      coronary heart disease.
AB  - We studied the value of serum amyloid A (SAA), a first-class acute-phase protein,
      as a marker for coronary heart disease (CHD) in a middle-aged male population. In
      a working population of 16307 men (age, 35-59 years), 446 cases had a history of
      CHD or prominent Q:QS waves on electrocardiogram. For each case, two matched
      controls were investigated. SAA, measured by immunonephelometry, was correlated
      with other acute-phase proteins, cardiovascular risk factors, and infectious
      serology markers. SAA concentrations were significantly higher in the cases than
      in controls (P<0.05) and correlated with serum C-reactive protein (CRP) (r=0.61),
      plasma fibrinogen (r=0.39), serum haptoglobin (r=0.26), and body mass index
      (r=0.13) (P<0.001). Serum CRP is a better marker for CHD than SAA, which showed
      discriminative power only in a univariate model comparing highest versus lowest
      tertile (odds ratio, 1.39; 95% confidence interval, 1.03-1.87). Neither SAA nor
      other acute-phase proteins correlated with Chlamydia pneumoniae immunoglobulin
      (Ig)G, Helicobacter pylori IgG and IgA, and cytomegalovirus IgG. In conclusion,
      although SAA has a discriminative value for CHD, serum CRP is to be preferred as
      a first-class acute-phase reactant for detection of the disease.

PMID- 11849672
TI  - Association between low serum enterolactone and increased plasma F2-isoprostanes,
      a measure of lipid peroxidation.
AB  - Evidence suggests that low serum enterolactone concentration might be an
      independent risk factor for acute coronary events. Enterolactone is a lignan,
      which is formed by intestinal bacteria from precursors in plant foods. Due to the
      biphenolic structure of enterolactone, it could act as an antioxidant and through
      this contribute to cardiovascular health. The aim of this study was to test the
      hypothesis that a low serum enterolactone concentration is associated with
      increased in vivo lipid peroxidation, assessed by plasma F2-isoprostane
      concentrations. We investigated this association in a subset of participants in
      'The Antioxidant Supplementation in Atherosclerosis Prevention' (ASAP) study. Out
      of 256 male participants a subsample of 100 consecutive men from baseline was
      selected for F2-isoprostane assays. The mean serum enterolactone concentration
      was 16.6 nmol/l and that of F2-isoprostanes 29.6 ng/l. The correlation
      coefficient for association between serum enterolactone and F2-isoprostane
      concentrations was -0.30 (P<0.003). Plasma F2-isoprostane levels decreased
      linearly across quintiles of serum enterolactone concentration (P=0.008 for a
      linear trend). In a multivariate model, enterolactone persisted as a significant
      predictor after adjustment for vitamins and other variables, with the strongest
      associations with F2-isoprostanes. Our present data suggest that low serum
      enterolactone concentration is associated with enhanced in vivo lipid
      peroxidation in men.

PMID- 11849675
TI  - Progression of coronary atherosclerosis quantified by analysis of 3-D
      reconstruction of left coronary arteries.
AB  - OBJECTIVES: Quantitative measurements on three-dimensional (3-D) reconstructed
      coronary trees permit accurate evaluation of vascular volumes, lengths and
      diameters. We applied this technique to investigate diffuse luminal narrowing in
      patients with the clinical manifestation of progressive atherosclerosis. METHODS:
      In 13 patients who presented repeatedly for coronary angioplasty (at least 4
      years of invasive follow-up), left coronary arteries were reconstructed in 3-D
      from biplane coronary angiograms. Mean diameter, cross-sectional areas, total
      length, and volume were calculated for segments and branches. Five patients
      without coronary artery disease served as controls. RESULTS: Patients with
      progressive coronary atherosclerosis demonstrated a significant reduction of
      total vascular volumes, mean diameters and cross-sectional areas at the initial
      investigation when compared with controls. Progressive luminal shrinkage occurred
      during follow-up (-0.04+/-0.13 mm per year and per segmental diameter). The
      progress of luminal narrowing in patients with coronary artery disease is related
      to the number of coronary risk factors and the duration of follow-up. CONCLUSION:
      Quantitative measurements on 3-D reconstructed coronary trees are a useful
      investigative tool for the assessment of progression of coronary atherosclerosis.

PMID- 11849674
TI  - Baseline intestinal absorption and synthesis of cholesterol regulate its response
      to hypolipidaemic treatments in coronary patients.
AB  - Baseline cholesterol metabolism was hypothesized to regulate responses of
      cholesterol synthesis and absorption, and serum cholesterol lowering to
      hypolipidaemic treatment. Thus, serum cholesterol and non-cholesterol sterols
      were measured before and during long-term simvastatin treatment (inhibition of
      cholesterol synthesis) and subsequent combination of statin with plant stanol
      ester margarine (inhibition of cholesterol absorption) consumption in subjects
      with low (n=15) and high (n=15) absorption of cholesterol, defined by respective
      low and high baseline ratios of serum cholestanol to cholesterol. Cholesterol
      synthesis (defined by precursors of cholesterol) was markedly reduced by the long
      term statin treatment in both groups, but more extensively in the low than high
      absorption group (P<0.05), yet the respective serum cholesterol reductions were
      similar. From among the absorption markers, sitosterol and cholestanol ratios
      were correspondingly increased more in the low than in the high absorption group.
      Plant stanol ester margarine consumption, combined with chronic statin treatment,
      further lowered the serum cholesterol level (P<0.001) only in the high absorption
      group. The sum of cholesterol absorption markers was reduced more (P<0.05) in the
      high than in the low absorption group, while the non-significant serum
      cholesterol reduction of the low absorption group was associated with relatively
      high increase of cholesterol synthesis. Thus, stanol ester margarine combined
      with chronic simvastatin treatment reduces cholesterol absorption and serum
      cholesterol more consistently in subjects with high than low baseline absorption
      of cholesterol. The profile of baseline cholesterol metabolism determines the
      changes in synthesis and absorption of cholesterol to hypolipidaemic treatments,
      but affects less differently serum cholesterol level.

PMID- 11849676
TI  - Increased intra-abdominal fat may lower HDL levels by increasing the fractional
      catabolic rate of Lp A-I in postmenopausal women.
AB  - High-density lipoprotein (HDL) particles without apolipoprotein A-II (Lp A-I) may
      be more anti-atherogenic than HDL with apo A-II (Lp A-I/AII) and Lp A-I is
      reported selectively to be reduced in cases of intra-abdominal obesity. We
      explored the mechanisms of this reduction by studying the turnover of Lp A-I and
      Lp A-I/A-II in postmenopausal women well characterized for total body, regional
      and sub-regional adiposity by body mass index (BMI), truncal girth ratio, and
      abdominal magnetic resonance imaging (MRI), respectively. We tested for possible
      cause-effect relationships by measuring inter-correlations among these variables.
      Intra-abdominal fat area correlated strongly and positively with the fractional
      catabolic rate (FCR) of Lp A-I (r=0.98, P=0.003). Intra-abdominal fat only showed
      a non-significant trend toward correlation with the FCR of Lp A-I/A-II (r=0.84,
      P=0.07), and had no correlation with the production or transport rate (TR) of
      either Lp A-I or Lp A-I/A-II (r=0.48 and 0.02, respectively, P>0.1). Subjects
      were studied both with and without estrogen replacement, allowing exploration of
      a possible interaction of adiposity with estrogen effects on HDL turnover.
      Response of HDL turnover to estrogen did not correlate with adiposity, except for
      a parameter of waist to hip ratio (WHR), which predicted the increase in LP A-I
      TR with estrogen (r=0.84, P=0.04). We conclude that intra-abdominal fat may lower
      HDL levels by increasing the FCR of Lp A-I, suggesting a mechanism by which
      central adiposity may be proatherogenic.

PMID- 11849678
TI  - Herpes-like virus detection in infected Crassostrea gigas spat using DIG-labelled
      probes.
AB  - An in situ hybridization protocol for detecting the herpes-like virus which
      infects French Pacific oysters, Crassostrea gigas, was developed. Two DNA probes
      were synthesized by incorporation of digoxigenin 11-dUTP during PCR. Two oyster
      herpes-like virus specific primer pairs, A5/A6 and C1/C6, were used. Both DIG
      labelled probes were able to detect 50 pg of herpes-like virus PCR amplified DNA
      in Southern blot hybridizations. The probes hybridized with viral DNA in paraffin
      sections of infected C. gigas spat. No non-specific binding was observed. The
      ability of the defined in situ hybridization technique to diagnose herpes-like
      virus infections in oysters was compared with light and transmission electron
      microscopy techniques in infected and non-infected spat. In situ hybridization
      assays were also conducted on paraffin sections to determine virus distribution
      within the host and to study the pathogenesis infection. In situ hybridization
      confirmed that the expression pattern of the herpes-like virus was restricted to
      connective tissues as described previously by light and transmission electron
      microscopy. However, this technique also allowed the detection of viral DNA in
      the oyster nervous system. Some labelled cells were observed in the visceral
      ganglion of infected oyster spat.

PMID- 11849679
TI  - Differentiation of subtypes B and E of human immunodeficiency virus type 1 by
      polymerase chain reaction using novel env gene primers.
AB  - Novel sets of env gene PCR primers for distinguishing human immunodeficiency
      virus type 1 (HIV-1) subtypes B and E were designed. These primers anneal to
      different regions of the env gene and amplify DNA fragments of distinct sizes in
      a subtype-specific manner. Blood samples from 11 HIV-1 carriers in Thailand and
      46 carriers in Japan were examined by PCR. The new env primers detected HIV-1
      proviral DNA in 100% (11/11) and 88% (37/42) of the subtype B and E infection
      cases, respectively. The env primers also detected proviral DNA in saliva and
      breast milk samples in seven of 11 cases and two of three cases, respectively.
      The PCR subtyping results matched completely with those obtained by nucleotide
      sequencing of the env V3 region. The results suggest that the PCR using the env
      primers designed in this study may be an accurate and cost-effective method for
      differentiating subtypes B and E of HIV-1 in a large number of clinical samples.
      However, subtype E specific primer cross-react with subtype A, C, G, the new
      primer in this study is useful for regions in South East Asia where subtype E is
      predominant.

PMID- 11849681
TI  - Detection of HCV RNA in saliva of patients with hepatitis C virus infection by
      using a highly sensitive test.
AB  - Hepatitis C virus (HCV) is transmitted primarily by direct percutaneous exposures
      to blood. Since HCV RNA has been found in saliva, it has been suggested that
      saliva might also be a source of infection. HCV RNA in saliva from plasma HCV RNA
      positive patients was tested by a highly sensitive PCR method. HCV RNA was
      detected in 32 out of 61 saliva specimens (52.4%). No correlation was found
      between the presence of HCV in saliva and age, sex, identified risk factors for
      HCV infection, time lapsed since the diagnosis, transaminases and alkaline
      phosphatase values and stimulated salivary flow. A statistically significant
      relation between plasma HCV RNA viral load and saliva HCV RNA detection was
      observed (P<0.001). In conclusion, HCV RNA is often present in saliva of HCV
      infected patients, with plasma viral load being the only known predictable
      factor. Further studies on salivary HCV RNA are needed.

PMID- 11849680
TI  - Detection of equine arteritis virus by real-time TaqMan reverse transcription-PCR
      assay.
AB  - A one-tube real-time TaqMan reverse transcription-polymerase chain reaction (RT
      PCR) assay was developed for the detection of equine arteritis virus (EAV). The
      test was validated using the seminal plasma and nasal secretions of infected
      horses that were proven to contain EAV by traditional virus isolation in rabbit
      kidney thirteen (RK-13) cells, as well as a variety of cell culture-propagated
      European and North American strains of EAV. The primers and a fluorogenic TaqMan
      probe were designed to amplify and detect a highly conserved region of open
      reading frame 7 (ORF7) of EAV. The real-time TaqMan PCR assay detected EAV RNA in
      all samples that were confirmed to contain infectious EAV by virus isolation. The
      assay had an analytical sensitivity of 10 molecules of EAV RNA allowing the
      detection of EAV in clinical samples or tissue culture fluid (TCF) containing at
      least 200 viral RNA copies per ml. Thus, the one-tube real-time TaqMan RT-PCR
      assay provides a rapid, accurate, quantitative, convenient and high sample
      throughput system for diagnosis of EAV infection, in a closed-tube format that
      minimizes the risk of cross-contamination.

PMID- 11849682
TI  - The detection of Tomato spotted wilt virus (TSWV) in individual thrips using real
      time fluorescent RT-PCR (TaqMan).
AB  - Tomato spotted wilt virus (TSWV) is an important virus, economically in the UK,
      causing damaging disease in ornamental and vegetable crops. The virus is vectored
      by several species of thrips, most importantly the western flower thrips
      (Frankliniella occidentalis Pergande [Thysanoptera: Thripidae]). The vector
      thrips themselves constitute a damaging pest and are difficult to control
      completely. Monitoring thrips numbers is an important part of the control of
      virus, but does not give information on how many of the thrips are viruliferous.
      Monitoring the presence of viruliferous thrips at an early stage of an epidemic
      may lead to improved disease control, since virus can be spread effectively
      whilst vector pressure is low and symptoms may take several weeks to appear on
      some hosts. This paper describes the development of a sensitive and robust, high
      throughput method for the detection of TSWV in individual insects based on TaqMan
      chemistry. The method incorporates a novel RNA specific internal control to
      increase the reliability of the results. Results are also presented on
      comparisons of different extraction methods, including insects taken from sticky
      traps, for high-throughout testing. Implementation of a method such as this for
      the reliable detection of TSWV in individual thrips would aid the understanding
      of the progress of TSWV epidemics, and offer an early disease warning system for
      growers.

PMID- 11849684
TI  - Simultaneous RT/PCR detection and differentiation of arabis mosaic and grapevine
      fanleaf nepoviruses in grapevines with a single pair of primers.
AB  - The movement protein genes from several isolates of ArMV and GFLV of different
      geographical origins were amplified by RT/PCR using degenerate primers, cloned
      and sequenced. A single pair of degenerate primers was designed from these
      sequences to allow the simultaneous amplification of parts of the movement
      protein genes of ArMV and GFLV. Their use in an immunocapture-RT/PCR for the
      detection of ArMV or GFLV in infected grapevines proved to be ten times more
      sensitive than the corresponding ArMV or GFLV ELISA tests. A Sph1 restriction
      site found in the sequences corresponding to the amplified products from the GFLV
      isolates, but not in the amplified products from the ArMV isolates, allowed the
      differentiation between ArMV and GFLV in the infected grapevines by a Sph1
      restriction digestion of the amplified products.

PMID- 11849683
TI  - Potential of bovine herpesvirus 4 as a gene delivery vector.
AB  - A cloning system was developed for construction of BHV-4 recombinants and
      recombinant virus BHV-4EGFPDeltaTK containing an enhanced green fluorescent
      protein (EGFP) gene was constructed. The host range of BHV-4EGFPDeltaTK was
      characterized in vitro. When cell lines from various species and tissues were
      infected, most of the non-bovine cell lines exhibited neither cytopathic effect
      (CPE) nor supported viral replication, but EGFP expression was clearly observed.
      Next, embryonic stem cells were infected and induced to either non-specific or
      neural differentiation to determine whether they could survive and differentiate
      after BHV-4EGFPDeltaTK infection. Embryonic stem cells were infected
      successfully, as indicated by EGFP expression prior to differentiation, and EGFP
      expression could be detected in many differentiated cells. No CPE was noted.
      Therefore, BHV-4EGFPDeltaTK infection caused neither cell death nor interfered
      with non-specific or neural differentiation of embryonic stem cells. Finally, to
      assess the capability of BHV-4EGFPDeltaTK to infect post-mitotic neurons,
      cultures from brains of 2-weeks old mice were infected. No death of neuronal
      cells due to infection was observed and EGFP expression persisted for at least 15
      days. Several biological characteristics of BHV-4 demonstrated previously make it
      a good candidate for a gene delivery vector. These include: little or no
      pathogenicity, unlikely oncogenicity, ability to establish persistent infection,
      and capability of herpesviruses to accommodate large amounts of foreign genetic
      material. These findings add the ability to infect several cell types coming from
      different animal species, usually without CPE, lack of interference with
      differentiation, and ability to maintain transgene expression in both
      undifferentiated and differentiated cells.

PMID- 11849685
TI  - Use of a swine bioassay and a RT-PCR assay to assess the risk of transmission of
      swine hepatitis E virus in pigs.
AB  - The objective of this study was to assess the risk of transmission of swine
      hepatitis E virus (swine HEV) to naive pigs by inoculation with tissues or feces
      collected from pigs infected experimentally with swine HEV. Seventy-five, 3-week
      old pigs were assigned randomly to 24 groups of 3-4 pigs and inoculated with
      homogenates of tissues (liver, heart, pancreas, or skeletal muscle) or a
      suspension of feces from swine HEV-infected pigs collected at 3, 7, 14, 20, 27,
      or 55 days post inoculation (DPI). Each inoculum was prepared as a 10% suspension
      (w/v) in PBS buffer and tested by a semi-quantitative RT-PCR for swine HEV RNA
      and by the swine bioassay. The inoculation route was intravenous for liver, heart
      and pancreas, and via stomach tube for skeletal muscle and fecal suspension. The
      liver homogenate inocula and feces collected at 3-7 and 14-20 DPI were positive
      for swine HEV RNA by RT-PCR. The pigs inoculated with liver homogenates collected
      at 3-7 and 14-20 DPI developed anti-HEV antibodies and swine HEV RNA was detected
      in their sera. Pigs inoculated with heart, pancreas, skeletal muscle homogenates
      or fecal suspensions failed to develop anti-HEV antibodies. These findings
      suggest that there is a potential risk of transmission of swine HEV via liver
      tissue from infected pigs in the early stages (3-20 DPI) of infection and the in
      vitro RT-PCR assay correlates well with the swine bioassay.

PMID- 11849686
TI  - Validation of a luminescence immunoassay for the detection of PrP(Sc) in brain
      homogenate.
AB  - A luminescence immunoassay (LIA) was developed for the diagnosis of bovine
      spongiform encephalopathy (BSE) in brain tissue using two different monoclonal
      antibodies for capture and detection of the protease-resistant fragment of the
      pathological prion protein (PrP27-30). PrP27-30 currently represents the most
      reliable marker for the infectious particle (denominated prion) causing
      transmissible spongiform encephalopathies (TSEs). Internal and official
      validation studies of this assay are described using brain homogenates from
      ascertained BSE positive and negative cows. Using more than 300 positive and 1400
      negative bovine or ovine samples, an excellent sensitivity and specificity of
      100% were demonstrated. More than 1000-fold dilutions of a BSE positive
      homogenate still resulted in a clear positive signal. In combination with a
      simple homogenisation procedure for the preparation of the samples, this assay
      lends itself for large scale screening of cattle and sheep for TSEs using
      complete automation of the process.

PMID- 11849687
TI  - Distribution of rabies antigen in infected brain material: determining the
      reliability of different regions of the brain for the rabies fluorescent antibody
      test.
AB  - To assist in making recommendations for sampling of brains for the fluorescent
      antibody test (FAT), a study was conducted to determine the regions of the brain
      where rabies antigen is found most reliably. Each identifiable part of 252 rabies
      positive brains of various species was re-tested using routine FA tests. It was
      found that there was frequent variation in the quantity of antigen between
      regions of the brain. The thalamus, pons and medulla were the most reliable parts
      of the brain as they were positive in all specimens tested. The cerebellum,
      hippocampus and different parts of the cerebrum were negative in, respectively,
      4.5, 4.9 and 3.9-11.1% of positive brains. It is recommended that specimens for
      rabies diagnosis must include the brain stem. The structure of choice would be
      the thalamus as it was positive in all specimens and had the most frequent
      prevalence (97.8%) of abundant antigen. These findings contradict many old
      studies that state that the hippocampus should be the structure of choice for
      rabies diagnosis. The current data demonstrate that the reason for the old
      recommendations is that the hippocampus has the highest frequency of large
      inclusion bodies, as the reliability of the histological tests used previously
      depended on inclusion body size.

PMID- 11849688
TI  - Quantitation of cucurbit yellow stunting disorder virus in Bemisia tabaci (Genn.)
      using digoxigenin-labelled hybridisation probes.
AB  - A cost-efficient hybridisation assay was developed to estimate the amount of
      cucurbit yellow stunting disorder virus (CYSDV) in Bemisia tabaci (Gennadius)
      whiteflies infesting protected cucumber crops. cDNA from the coat protein (cp)
      gene and the hsp70 homologue protein gene from CYSDV were obtained by reverse
      transcriptase-PCR from viruliferous whiteflies and cloned into plasmids.
      Digoxigenin (DIG)-labelled cDNA probes reacted with extracts from these
      whiteflies applied on nylon membranes. Precision and linear ranges were
      established in a hybridisation analysis using known concentrations of unlabelled
      homologue cDNA. Extracts from non-viruliferous B. tabaci showed a concentration
      dependent effect on the assay with cp-specific probes but not with hsp70-specific
      probes. The hsp70 probe was used to evaluate natural B. tabaci populations in
      commercial cucumber crops, and the estimated amounts of CYSDV per whitefly were
      found ranging from 5.6 fg to approximately 2.5 pg of corresponding hsp70-cDNA.

PMID- 11849689
TI  - Standardization of denaturing gradient gel electrophoresis for mutant screening
      of influenza A (H3N2) virus samples.
AB  - Because of the extensive genetic variability of the influenza viruses, new virus
      mutants arise worldwide. In the human population, some strains may become
      potentially epidemic after evading the immune response of the host. At present,
      molecular methods have made it possible to identify these variants. However, if a
      large number of samples need to be analyzed the identification of randomly
      mutated nucleotides cannot be achieved by sequencing analysis or restriction
      fragment length polymorphism (RFLP). In order to improve this process, a
      denaturing gradient gel electrophoresis (DGGE) protocol capable of discriminating
      between reference strains representative of different influenza seasons, some
      mutant strains, and five clinical isolates was standardized Ribonudeic acid (RNA)
      was isolated and submitted to a one-step RT-PCR that amplified the region
      codifying for the globular domain of the Haemagglutinin (HA) molecule. The
      amplicons were analyzed by electrophoresis in 6% polyacrylamide gel at 60
      degreeC/150 V for 8 h, using a 31--41% urea--formamide gradient. This method was
      able to distinguish between closely related nucleotide sequences, confirming its
      suitability as screening methodology for the analysis of influenza virus
      epidemiology, by allowing a faster and more extensive evaluation of a large
      number of the variant strains detected in a specific region of the world.

PMID- 11849691
TI  - Comparison of three methods for respiratory virus detection between induced
      sputum and nasopharyngeal aspirate specimens in acute asthma.
AB  - Viral respiratory tract infections are associated frequently with acute
      exacerbations of asthma. Nasopharyngeal aspirates and bronchoalveolar lavage
      specimens are used extensively for detecting viral respiratory tract infections,
      but not sputum. The aim of the study was to determine the efficiency of viral
      detection in induced sputum versus nasopharyngeal aspirate obtained during acute
      exacerbations of asthma, comparing three laboratory methods of viral diagnosis.
      Paired samples of induced sputum and nasopharyngeal aspirate obtained from 32
      adults admitted to hospital with acute asthma were subjected to reverse
      transcription-polymerase chain reaction (RT-PCR), viral culture, and
      immunofluorescence assay. The results show that RT-PCR was associated with
      significantly higher rates of viral detection than culture (P=0.005) or
      immunofluorescence (P=0.001), without significant differences in the rates of
      viral detection between induced sputum and nasopharyngeal aspirate. It is
      concluded that induced sputum specimens are feasible for detection of viral
      respiratory tract infections by RT-PCR during acute exacerbations of asthma.

PMID- 11849690
TI  - High frequency of mixed TT virus infections in healthy adults and children
      detected by a simplified heteroduplex mobility assay.
AB  - Recombinant plasmids carrying 199 base pairs (bp) inserts from the non coding
      region (nucleotides (nt) 6-204) of the TT virus (TTV) genome were used to
      standardize an heteroduplex mobility assay able to detect mixed infections of a
      single individual with several TTV isolates. In this simplified heteroduplex
      mobility assay, polymerase chain reaction (PCR) products were analyzed directly
      by polyacrylamide gel electrophoresis, without requirement for post-PCR
      denaturation and annealing steps of the amplicons. The assay was used to test TTV
      positive serum samples collected from healthy 1-7 years old children, 11-17 years
      old adolescents, and 24-39 years old blood donors living in Rio de Janeiro,
      Brazil, as well as TTV positive samples from Amazonian Indians. The results
      showed a very high frequency of multiple infection in all groups, with 20/30
      (67%), 31/33 (94%), 35/38 (92%), and 34/37 (92%) of the samples collected from
      children, adolescents, blood donors, and Amazonian Indians, respectively,
      containing more than one TTV genotype.

PMID- 11849692
TI  - Development of strain-specific real-time PCR and RT-PCR assays for quantitation
      of chicken anemia virus.
AB  - Chicken anemia virus (CAV) is a ubiquitous pathogen of poultry. A CAV specific
      TaqMan-based PCR and RT-PCR assay for real-time quantitation of viral load and
      relative quantitation of virus-specific transcript levels was developed.
      Detection of viral DNA copy number from infected MDCC-CU147 cells was determined
      by extrapolation from a CAV plasmid-based standard curve. Viral load increased
      proportionally with increasing cell number harvested, increasing from 4x10(2)
      copies in 250 cells with 38% virus positive cells in an indirect
      immunofluorescence assay to 8x10(5) copies in 250,000 cells with 64% infected
      cells. The estimated average viral copy number per infected cell ranged from 5 to
      14. Strain-specific primers were developed to distinguish between the Cux-1 and
      CIA-1 strains of CAV. These primers exhibited a 3 to 4 log differential in
      amplification comparing homologous versus heterologous virus-primer combinations.
      The sensitivity of the real-time assay was found to be comparable to a nested PCR
      assay using DNA samples from a SPF poultry flock exposed to the SH-1 strain of
      CAV. The real-time PCR detected from 1.7 to 4.2 target molecules in three out of
      four samples that were positive by nested PCR using 50% of the DNA used in the
      nested PCR. Relative viral transcript levels for Cux-1 and CIA-1 infected cell
      cultures increased proportionally with increasing cell numbers harvested for RNA
      extraction. This assay will be important for both diagnosis and in understanding
      the complex pathogenesis of CAV infection.

PMID- 11849693
TI  - Performance characteristics of an automated PCR assay for the quantification of
      cytomegalovirus DNA in plasma.
AB  - The COBAS Amplicor CMV Monitor test (Roche Diagnostics), an automated polymerase
      chain reaction (PCR) assay for the quantification of cytomegalovirus (CMV) DNA in
      plasma samples, was evaluated in a routine diagnostic laboratory. Using cell
      culture-derived CMV and CMV-negative human plasma, the linear detection range of
      the assay as well as its intra-and inter-assay variabilities were assessed. The
      study design allowed distinguishing variations in results related to
      amplification and detection from those caused by differences in the efficiency of
      DNA extraction. The assay was able to identify the majority of samples correctly
      as positive with CMV DNA concentrations above the limit of detection. However,
      the reported values were often twofold or more different from the (theoretical)
      input, which could be explained partly by inefficient DNA extraction. The
      following values were computed for the coefficients of determination R(2): inter
      assay variability excluding DNA extraction, R(2)=0.982; including DNA extraction,
      R(2)=0.977; intra-assay variability excluding DNA extraction, R(2)=0.992;
      including DNA extraction, R(2)=0.992. On balance, the test has acceptable within
      run and between-run reproducibility. It therefore allows the comparison of
      results obtained at different time-points as well as in different laboratories,
      e.g. in multi-centre studies.

PMID- 11849694
TI  - Quantitation of hepatitis C virus RNA by third generation branched DNA-based
      signal amplification assay.
AB  - Quantitation of hepatitis C virus (HCV) RNA has become an important tool in
      different clinical settings and is used extensively for pretreatment evaluation
      of patients infected chronically with HCV. In this study, the performance
      characteristics of the third generation branched DNA-based signal amplification
      assay (bDNA 3.0) for HCV RNA quantitation were established. The new assay version
      showed an analytical specificity of 98%. Mean intra- and between-run imprecisions
      were 6.8 and 11.2%, respectively. The assay was linear over its entire dynamic
      range. Quantitation appeared to be unaffected by the genotypic variability of
      HCV. A comparison of bDNA 3.0 with the second generation bDNA assay calibrated
      against the international WHO HCV RNA standard, and the PCR-based Cobas Amplicor
      HCV Monitor 2.0 revealed a fairly good correlation among the assays. Twenty-nine
      and 11% of the paired quantitative results differed by more than log(10)0.5 (i.e.
      three-fold). All three assays after calibration against the WHO standard also
      yielded clinically comparable results with regard to the tailoring of interferon
      alpha/ribavirin treatment duration in patients infected by HCV genotypes 1, 4,
      and 5.

PMID- 11849695
TI  - Marek's disease virus genome separation from feather tip extracts by pulsed field
      gel electrophoresis.
AB  - Marek's disease virus is an oncogenic herpes virus of poultry that is highly cell
      associated. In the infected tissues and tumors the virus replicates in a low copy
      number. The propagation and dissemination of the virus takes place at the feather
      follicle epithelium, where the viral genome is produced in high copy number. As
      the viral genome is a large circular DNA molecule (200 kbp), pulsed field gel
      electrophoresis was used for separation of the viral genome directly from the
      infected chicken. DNA was extracted from tumors or feather tips by the
      phenol:chloroform technique or by low melting agar technique. It was found that
      feathers, being the site of virus productive replication, are useful for
      separation of free Marek's disease virus DNA from in vivo infections.

PMID- 11849696
TI  - Development of a molecular method to identify hepatitis E virus in water.
AB  - Hepatitis E virus (HEV) causes an infectious form of hepatitis associated with
      contaminated water. By analyzing the sequence of several HEV isolates, a reverse
      transcription-polymerase chain reaction method was developed and optimized that
      should be able to identify all of the known HEV strains. When tested under
      laboratory conditions, this method was able to detect low levels of five diverse
      HEV variants. In addition, internal controls were constructed so that any PCR
      inhibition could be detected. Finally, virus-spiked environmental water samples
      were analyzed successfully with these assays.

PMID- 11849697
TI  - Rapid methods for identification of poliovirus isolates and determination of
      polio neutralizing antibody titers in human sera.
AB  - A new rapid method for identification and determination of the titer of
      polioviruses and other enteroviruses in cell monolayers grown in microtiter
      plates is described. The method is based on immunoperoxidase staining of infected
      cells with commercial monoclonal antibodies (MAb) and biotin-labeled secondary
      antibody. The presence of poliovirus or other enteroviruses was established as
      the appearance of at least one focus of cells with stained cytoplasm 6 h post
      infection. Viral titers determined by this method were expressed as focus forming
      unit (FFU) per ml which was found to correspond approximately to 10 TCID(50)/ml.
      The suitability of this technique to determine poliovirus antibody titers in
      human sera was also tested comparing the immunocytochemical neutralization assay
      with a conventional neutralization in microtiter plates. The test was
      standardized using reference human sera in order to produce antibody titers
      expressed in international units (IU). In addition to high reproducibility, the
      new neutralization test appears to be sensitive, specific and rapid, and might
      thus represent a useful tool for the diagnosis of polio and other enterovirus
      infections.

PMID- 11849698
TI  - Detection of encephalomyocarditis virus in clinical samples by immunomagnetic
      separation and one-step RT-PCR.
AB  - A method of immunomagnetic separation and one-step reverse transcription
      polymerase chain reaction (RT-PCR) was developed for the detection of
      Encephalomyocarditis virus (EMCV). EMCV was captured from sample on magnetic
      beads with homologous monoclonal antibody and then heat denatured. The heated
      beads were used directly in one-step RT-PCR reaction to amplify a 285-bp PCR
      fragment at the 3' end of the genomic region that encodes the viral polymerase.
      This method detected as little as 3.5 TCID(50) of EMCV from infected cell
      culture. It was shown with this method that the sensitivity of RT-PCR increased
      when applied for the detection of EMCV added to fecal extract. Using this
      protocol EMCV was detected from heart homogenate samples containing less than 100
      TCID(50)/ml. The amplified product was sequenced to ensure specificity. The
      immunomagnetic-RT/PCR procedure described here should be useful for the rapid,
      specific and sensitive detection of EMCV in clinical samples. This technique is
      rapid, reliable and can be readily adapted to detect EMCV from other clinical
      samples.

PMID- 11849699
TI  - Growth and isotopic labelling of adherent cells in small volumes of medium.
AB  - The in vivo labelling of viral or cellular components is usually conducted
      through the addition of radioactively labelled precursors to the culture medium.
      A limiting factor for isotope use is often the cost of isotope purchase and
      disposal. Therefore, significant savings can be achieved if the smallest possible
      volume of medium is employed. However, in the case of adherent cells growing in
      tissue culture dishes or multi-well plates, surface tension causes a very uneven
      distribution of the liquid due to the formation of a meniscus at the edge of the
      petri. This prevents the use of very small volumes of medium for cell growth and
      labelling because the cells at the center of the petri dish would dry out and
      die, especially after longer incubation periods. In this communication, we
      describe a technique whereby cells are grown in an area surrounded by a
      hydrophobic ring of Teflon, which greatly improves the distribution of the medium
      by eliminating the concave meniscus. This translates into a dramatic improvement
      in the condition of the cells, as well as the efficiency of labelling of
      phosphoproteins, such as the Simian Virus 40 large tumor antigen with 32P
      orthophosphate or labelling of the cellular DNA with 3[H]thymidine. The technique
      is useful for any application where growth of cells in small volumes of medium is
      required.

PMID- 11849700
TI  - A nonisotopic assay method for hepatitis C virus NS5B polymerase.
AB  - The RNA-dependent RNA polymerase of hepatitis C virus (HCV) is responsible for
      replication of genomic RNA. A novel nonisotopic assay method is described for
      detecting its enzymatic activity. The 5' end of the in vitro-transcribed template
      RNA was attached covalently to the surface of a Covalink module using
      carbodiimide condensation. The RNA strand containing the 3' untranslated region
      (3' UTR) of HCV at its 3' end was free in the solution. A purified NS5B
      polymerase and NTPs along with biotin-labeled UTP were added to this module and
      the polymerization activity could be detected colorimetrically with streptavidin
      conjugated alkaline phosphatase.

PMID- 11849701
TI  - Cysteine proteases of parasitic organisms.
AB  - Cysteine proteases play numerous indispensable roles in the biology of parasitic
      organisms. Aside from previously known general catabolic functions and protein
      processing, cysteine proteases may be key to parasite immunoevasion,
      excystment/encystment, exsheathing and cell and tissue invasion. Parasite
      cysteine proteases are unusually immunogenic and have been exploited as
      serodiagnostic markers and vaccine targets. Although host homologues exist,
      parasite cysteine proteases have distinct structural and biochemical properties
      including, pH optima and stability, the alteration in peptide loops or domain
      extensions, diverse substrate specificity and cellular location. The disparate
      nature of parasite cysteine protease compared to the host orthologous proteins
      has opened opportunities for chemotherapy. This review will highlight recent
      research on the 'papain-like' class of cysteine proteases, the most abundant
      family, and the newly discovered class of asparaginyl-endopeptidases. Cysteine
      protease classification will be re-examined in light of the diversity uncovered
      within parasitic organisms.

PMID- 11849702
TI  - Endoribonuclease activities of Trypanosoma brucei mitochondria.
AB  - RNA editing in kinetoplastids is a type of post-transcriptional processing that
      changes mitochondrial mRNA sequences by the addition or deletion of uridines.
      Multiple enzymatic activities, such as endoribonuclease and RNA ligase, are
      associated with this process and exist in a multienzyme complex. Endonuclease
      activities from Trypanosoma brucei mitochondrial extracts were fractionated by
      sequential ion exchange and gel filtration chromatography. The RNA editing
      specific endonuclease activity co-fractionated with in vitro editing while
      another endonuclease activity with a different substrate specificity, and the
      majority of mtRNase P activity fractionated away from the editing activity. The
      pH, salt, temperature, and Mg(2+) optima of all three endonucleases were
      determined. All three activities are sensitive to high temperature and protease
      digestion. In addition, treatment with micrococcal nuclease resulted in partial
      disruption of the editing complex and decreased pre-cleaved in vitro insertion
      editing activity, suggesting that both RNA(s) and protein(s) are necessary in the
      intact functional complex.

PMID- 11849703
TI  - Targeted gene deletion in Leishmania major identifies leishmanolysin (GP63) as a
      virulence factor.
AB  - Leishmanolysin, the Leishmania surface metalloproteinase of 63 kDa (GP63) has
      been described as a parasite virulence factor and is involved in the direct
      interaction of promastigotes and host macrophage receptors and interaction with
      the complement cascade. To study the role of leishmanolysin in the pathogenesis
      and virulence of Leishmania major, targeted gene replacement was used to delete
      the entire 20 kb region containing all seven leishmanolysin genes (gp63 genes 1
      7). The resulting L. major leishmanolysin deficient mutants showed normal
      development inside the sand fly vector, however, promastigotes recovered from
      sand flies or from culture showed an increase in sensitivity to complement
      mediated lysis and a delay in lesion formation in BALB/c animals. The phenotypic
      differences could be significantly improved by expression of a cloned
      leishmanolysin gene. These results demonstrate that leishmanolysin is a vital
      virulence factor in Leishmania pathogenesis.

PMID- 11849704
TI  - Merozoite surface protein-9 of Plasmodium vivax and related simian malaria
      parasites is orthologous to p101/ABRA of P. falciparum.
AB  - Plasmodium vivax merozoite surface protein-9 (Pvmsp-9) is characterized here
      along with orthologues from the related simian malarias Plasmodium cynomolgi and
      Plasmodium knowlesi. We show that although the corresponding MSP-9 proteins do
      not have acidic-basic repeated amino acid (aa) motifs, they are related to the
      Plasmodium falciparum acidic-basic repeat antigen (ABRA) also known as p101.
      Recognition of this new interspecies Plasmodium MSP family stems from the prior
      identification of related MSP termed PvMSP-185, PcyMSP-150, and PkMSP-110 on the
      surface of P. vivax, P. cynomolgi and P. knowlesi merozoites. A clone containing
      the nearly complete P. knowlesi gene encoding PkMSP-110/MSP-9 provided a
      hybridization probe and initial sequence information for the design of primers to
      obtain the P. vivax and P. cynomolgi orthologues using polymerase chain reaction
      (PCR) amplification strategies. The P. vivax, P. cynomolgi and P. knowlesi msp-9
      genes encode proteins that range in calculated molecular mass from 80 to 107 kDa,
      have typical eukaryotic signal peptides and diverse repeated motifs present
      immediately upstream of their termination codon. Another feature conserved among
      these proteins, including the P. falciparum ABRA protein, is the positions of
      four cysteine residues near the N-terminus, suggesting this conservation
      maintains structural and perhaps functional characteristics in the MSP-9 family.
      Rabbit polyclonal antisera raised against recombinantly expressed N-termini of P.
      knowlesi and P. vivax MSP-9 cross-react with the counterpart proteins in
      immunofluorescence and immunoblot assays. Comparative interspecies investigations
      of the potential role(s) of Plasmodium MSP-9 in merozoite invasion of
      erythrocytes and as a malaria vaccine candidate can now be pursued.

PMID- 11849705
TI  - Avian anticoccidial activity of a novel membrane-interactive peptide selected
      from phage display libraries.
AB  - In the present work, we describe the discovery of PW2, a novel peptide presenting
      in vitro activity against Eimeria acervulina and E. tenella sporozoites. PW2 was
      selected from phage display (Ph.D.) peptide libraries by an alternative method of
      panning using living purified E. acervulina sporozoites as targets. Our results
      showed that the peptide disrupts the sporozoite pellicle, resembling the effect
      caused by most natural antimicrobial peptides. PW2 peptide was also effective
      against fungi and showed low activity against Toxoplasma gondii tachyzoites, but
      no activity against Trypanosoma cruzi, Crithidia fasciculata epimastigotes, and
      bacteria. Additionally, the parasiticidal concentrations of PW2 produced a very
      low lytic effect on mammalian and avian cells. The effectiveness against Eimeria
      sporozoites and the absence of adverse effects to host cells indicates that PW2
      may be used as a model to generate new drugs for the control of avian
      coccidiosis.

PMID- 11849706
TI  - Novel antifolate resistant mutations of Plasmodium falciparum dihydrofolate
      reductase selected in Escherichia coli.
AB  - A simple and effective system has been developed from which a number of
      Plasmodium falciparum dihydrofolate reductase (pfDHFR) mutants conferring
      resistance to antifolates were randomly generated and characterized. The system
      exploited error-prone PCR to generate random mutations in the pfDHFR. Using the
      synthetic gene encoding for wild-type and quadruple mutant
      (N51I+C59R+S108N+I164L) pfDHFRs as templates, mutants resistant to pyrimethamine
      (Pyr), m-Cl analogue of Pyr (SO3) and WR99210 were selected by bacterial
      complementation system in which the endogenous DHFR activity of bacterial host
      cells, but not of Plasmodium, is selectively inhibited by trimethoprim (Tmp).
      Mutants conferring resistance to antimalarial antifolates were selected under the
      condition that inhibited the growth of the wild-type pfDHFR. All obtained Pyr
      resistant mutants possessed S108 mutation, in combination with common mutations
      of N51I, C59R and I164L previously found in the field. New Pyr resistant mutants
      with novel mutations (K27T, N121D, N144K and V213E) not found in the field were
      also identified. Exposure of the randomly mutated pfDHFR libraries to WR99210 or
      SO3 resulted in selection of novel single and multiple mutants including D54N,
      F58L and a combination of C50R, K181R, T219P and K227E, which exhibited 2- to
      over 2000-fold increase in resistance against antifolates. Kinetic analysis of
      these mutants suggested that apart from the active site residues that are crucial
      for DHFR activity, residues remote from the binding pocket also play essential
      roles in substrate and inhibitor binding.

PMID- 11849707
TI  - The GPI1 homologue from Plasmodium falciparum complements a Saccharomyces
      cerevisiae GPI1 anchoring mutant.
AB  - Glycosylphosphatidylinositol (GPI) represents an important anchoring molecule for
      cell surface proteins. The first step in its synthesis is the transfer of N
      acetylglucosamine (GlcNAc) from UDP-N-acetylglucosamine to phosphatidylinositol
      (PI). This chemically simple step is genetically complex because three or four
      genes are required in both yeast (GPI1, GPI2 and GPI3) and mammals (GPI1, PIG A,
      PIG H and PIG C), respectively. Here, we report cloning of a Plasmodium
      falciparum (P. falciparum) homologue of GPI1 (PfGPI1). Analysis showed that P.
      falciparum Gpi1p is somewhat more similar to the yeast proteins than human Gpi1p,
      showing 26 and 20% amino acid sequence identity with the Saccharomyces cerevisiae
      and Homo sapiens proteins, respectively. Multiple sequence alignment demonstrates
      also that the C-terminal half GPI1 proteins is much better conserved than the N
      terminal half. The P. falciparum Gpi1p has a calculated molecular weight of 65
      kDa and a predicted potential tyrosine phosphorylation site. The potential
      tyrosine phosphorylation site seems to occur in all other known Gpi1 proteins.
      Like the other GPI1 proteins, the predictive software revealed the absence of
      targeting signals such as organelle transit peptides, DNA binding sites, or N
      terminal secretory signals. Hydrophobicity plots revealed multiple hydrophobic
      regions that could function as transmembrane segments. The cloned P. falciparum
      GPI1 gene complemented a gpi1 yeast mutant.

PMID- 11849708
TI  - Cellular signalling in Trypanosoma cruzi: biphasic behaviour of inositol
      phosphate cycle components evoked by carbachol.
AB  - Stimulation of epimastigote forms of Trypanosma cruzi with carbachol resulted in
      a long-lasting response. The earlier phase for inositol phosphates was rapid and
      transient, peaking at 1 min with a return to basal levels by 6 min. In a second
      phase, these metabolite levels reached maximal values at 10-12 min, with a later
      declination to basal values at about 20 min. The inositol phosphate response was
      quenched by parasite treatment with atropine. The elevation in intracellular free
      calcium ([Ca(2+)]i) was transient, reaching the resting level at 87+/-8 s (n=48)
      of agonist addition. Myo-inositol 1,4,5-triphosphate (InsP(3)) production and
      [Ca(2+)]i mobilisation were carbachol dose-dependent. The maximally effective
      concentrations of agonist ranged between 1x10(-6) and 1x10(-5) M. The increase in
      carbachol concentration resulted in an evident attenuation of [Ca(2+)]i
      mobilisation and in [3H]InsP(3) levels. Pretreatment of the cells with 10 microM
      U73122, a phospholipase C (PLC) inhibitor, showed that both InsP(3) peaks
      triggered by carbachol were completely abolished, whereas there was not
      substantial change on the maximum elevation in [Ca(2+)]i. The first peak of
      InsP(3) and InsP(s) was completely abolished when the cells were incubated with
      phorbol 12-myristate 13-acetate ester (TPA) for 30 min before carbachol
      stimulation. A biphasic behaviour for PtdIns 4-kinase activity was demonstrated
      by changes in [32P]PtdInsP levels. The time-course of PtdIns4P 5-kinase activity
      showed a rapid, significant and transient decrease of [32P]PtdInsP(2) from 0 time
      to the third min. At the end of this time the polyphosphoinositide began to
      return towards control levels but, interestingly, after 5-6 min of stimulation
      there was a subsequent more important increase over control levels which peaked
      at 10 min. There was also a detectable increment of DAG at 1 min with a maximum
      at 3 min, this level remaining elevated until at least 10 min. Subsequently,
      these levels returned to the base line or even below it.

PMID- 11849709
TI  - Variation in primary sequence and tandem repeat copy number among i-antigens of
      Ichthyophthirius multifiliis.
AB  - The immobilization antigens (i-antigens) of Ichthyophthirius multifiliis are
      potential vaccine candidates for the prevention of 'white spot' disease in
      freshwater fish. These antigens vary with respect to antigenicity and molecular
      mass, and at least five i-antigen serotypes have been identified among parasite
      isolates thus far. In previous studies, the gene and corresponding cDNA encoding
      a approximately 48 kDa i-antigen from parasite isolate G1 (serotype A), had been
      cloned and sequenced. We now report on the isolation of two new genes, designated
      IAG52A[G5] and IAG52B[G5], encoding approximately 52/55 kDa i-antigens from a
      parasite isolate representing a different serotype, namely, D. Based on their
      deduced sequences, the approximately 52/55 kDa gene products have the same
      structural features as the 48 kDa protein including hydrophobic N- and C-termini,
      periodic cysteine residues with the potential for metal binding, and tandemly
      repetitive amino acid sequence domains that span their length. Nevertheless, the
      products of these genes vary in their tandem repeat copy number, and share only
      approximately 50% homology overall. When expressed in heterologous systems, the
      products of the newly described genes react strongly with monospecific polyclonal
      antisera against the i-antigens of serotype D and are clearly i-antigens. It
      would nevertheless appear that mRNA transcripts from the two genes are present at
      widely different levels within parasites themselves. Analysis at the protein
      level using 2-D SDS-PAGE would further suggest that multiple i-antigens are
      expressed within the same serotype at any given time.

PMID- 11849710
TI  - Context-dependent roles of the Entamoeba histolytica core promoter element GAAC
      in transcriptional activation and protein complex assembly.
AB  - Transcriptional control of the hgl5 gene of Entamoeba histolytica is mediated
      through an unusual core promoter composed of TATA, GAAC and Initiator elements.
      In the hgl5 promoter the GAAC element (AATGAACT) determines the site and rate of
      transcription initiation. Here we tested the role of the GAAC element in
      transcription activation from upstream regulatory elements (UREs) in the hgl5
      promoter. We also examined the function of the GAAC element in the ferredoxin
      (fdx) promoter and characterized the protein binding to the GAAC element.
      Electrophoretic mobility shift assays (EMSA) demonstrated that the GAAC region is
      necessary for higher-order nuclear protein complex assembly. The function of the
      GAAC element in transcription activation mediated by UREs revealed that mutation
      of the GAAC element did not affect transcription activation mediated by the hgl5
      URE4 but abrogated activation by the hgl5 URE3. We compared the role of the GAAC
      elements in the hgl5 and fdx promoters. Competitive gel shift assays were
      consistent with the same nuclear protein binding to the GAAC elements in both
      genes. Mutation of the GAAC element in the fdx gene decreased reporter gene
      expression, however, in contrast to hgl5 gene, had no effect on the site of
      transcription initiation. These results support a role for the GAAC element in
      assembly of nuclear proteins at the core promoter and in transcription activation
      mediated by URE3. The differing effect on transcription initiation in the hgl5
      and fdx genes upon mutation of the GAAC element suggests a context-dependence of
      the GAAC-binding protein in gene expression.

PMID- 11849711
TI  - Genetic diversity of the DBLalpha region in Plasmodium falciparum var genes among
      Asia-Pacific isolates.
AB  - In Plasmodium falciparum a highly polymorphic multi-copy gene family, var,
      encodes the variant surface antigen P. falciparum erythrocyte membrane protein 1
      (PfEMP1), which has an important role in cytoadherence and immune evasion. Using
      previously described universal PCR primers for the first Duffy binding-like
      domain (DBLalpha) of var we analysed the DBLalpha repertoires of Dd2 (originally
      from Thailand) and eight isolates from the Solomon Islands (n=4), Philippines
      (n=2), Papua New Guinea (n=1) and Africa (n=1). We found 15-32 unique DBLalpha
      sequence types among these isolates and estimated detectable DBLalpha repertoire
      sizes ranging from 33-38 to 52-57 copies per genome. Our data suggest that var
      gene repertoires generally consist of 40-50 copies per genome. Eighteen DBLalpha
      sequences appeared in more than one Asia-Pacific isolate with the number of
      sequences shared between any two isolates ranging from 0 to 6 (mean=2.0 +/-1.6).
      At the amino acid level DBLalpha sequence similarity within isolates ranged from
      45.2 +/- 7.1 to 50.2 +/- 6.9%, and was not significantly different from the
      DBLalpha amino acid sequence similarity among isolates (P>0.1). Comparisons with
      published sequences also revealed little overlap among DBLalpha sequences from
      different regions. High DBLalpha sequence diversity and minimal overlap among
      these isolates suggest that the global var gene repertoire is immense, and may
      potentially be selected for by the host's protective immune response to the var
      gene products, PfEMP1.

PMID- 11849712
TI  - Proton and sodium pumps regulate the plasma membrane potential of different
      stages of Trypanosoma cruzi.
AB  - We studied the plasma membrane potential (DeltaPsi) in different stages of
      Trypanosoma cruzi using the potentiometric fluorescent dye bisoxonol. Our results
      clearly demonstrate that a proton pump plays a significant role in the regulation
      of DeltaPsi in all stages of T. cruzi as evidenced by depolarization of the
      DeltaPsi by H(+)-ATPase inhibitors dicyclohexylcarbo-diimide, N-ethylmaleimide,
      diethylstilbestrol, and bafilomycin A(1). The H(+)-ATPase appeared to be
      activated by acidic conditions in trypomastigotes as evidenced by
      hyperpolarization of the DeltaPsi upon addition of acid. In contrast to
      epimastigotes and amastigotes, the DeltaPsi of trypomastigotes was markedly
      sensitive to extracellular Na(+) and K(+) concentrations and evidence was
      provided for an outward directed Cl(minus sign) channel in this stage as well.
      Additionally, for the first time, the existence of an ouabain-sensitive
      functional sodium pump was demonstrated in T. cruzi based on the depolarization
      of the DeltaPsi in trypomastigotes by ouabain in the presence of Na(+). In the
      epimastigotes, ouabain had no effect on the DeltaPsi in a sodium rich buffer.
      However, ouabain induced an additional significant depolarization in these stages
      when their DeltaPsi was already partially depolarized by the H(+)-ATPase
      inhibitor dicyclohexylcarbo-diimide, supporting the presence of an ouabain
      sensitive sodium pump whose activity is masked by the H(+)-ATPase. In the
      amastigotes no evidence for a functional sodium pump could be found. In support
      of an inwardly directed K(+) channel, the DeltaPsi was hyperpolarized by K(+)
      free buffer in trypomastigotes and epimastigotes and by Ba(2+) in epimastigotes
      and amastigotes. The presence of K(+) channels in amastigotes and a sodium pump
      in trypomastigotes, in addition to the H(+)-ATPase, could provide important new
      targets for trypanocidal drug development.

PMID- 11849713
TI  - HSP70-controlled GFP expression in transiently transformed schistosomes.
AB  - Among the parasitic helminths schistosomes are of high medical and economic
      importance. Despite of the world-wide relevance of this parasite, very little is
      known about the cellular mechanisms controlling its development and concerning
      the host-parasite interaction. Within the last decade a great effort has been
      made in this blood fluke to identify genes which play important roles during
      these processes. However, molecular analysis was limited by the fact, that
      neither function nor regulation of candidate genes could be investigated in this
      organism due to the lack of transformation protocols. Here, we present the
      strategy of ballistic gene transfer to introduce and characterize transgenes in
      different schistosome life stages. As a transformation vector, the heat shock
      protein 70 (hsp70) gene promoter and terminator from Schistosoma mansoni were
      cloned and fused to the green fluorescent protein (GFP) reporter gene. In a first
      attempt, the hsp70--GFP vector was successfully tested in a eukaryotic cell line.
      Thereafter, adult male schistosomes and sporocysts were transformed with this
      vector, and GFP expression was demonstrated using molecular and microscopical
      methods. PCR, reverse transcriptase-polymerase chain reaction (RT-PCR) and
      Western blot analyses confirmed the presence, transcription and translation of
      the transgene in adults. Confocal laser scanning microscopy revealed GFP-activity
      at various sites along the surface of the worms after hs induction and within
      sporocysts. These results suggest diverse roles for hsp70 during the development
      of schistosomes. Furthermore, the results demonstrate the feasibility of this
      method and open the perspective to analyze a variety of molecular functions in
      schistosomes.

PMID- 11849714
TI  - Generation of myo-inositol-auxotrophic Leishmania mexicana mutants by targeted
      replacement of the myo-inositol-1-phosphate synthase gene.

PMID- 11849715
TI  - The Cryptosporidium parvum ABC protein family.

PMID- 11849717
TI  - Sensitivity and specificity of pooled faecal culture and serology as flock
      screening tests for detection of ovine paratuberculosis in Australia.
AB  - The flock-level sensitivity of pooled faecal culture and serological testing
      using AGID for the detection of ovine Johne's disease-infected flocks were
      estimated using non-gold-standard methods. The two tests were compared in an
      extensive field trial in 296 flocks in New South Wales during 1998. In each
      flock, a sample of sheep was selected and tested for ovine Johne's disease using
      both the AGID and pooled faecal culture. The flock-specificity of pooled faecal
      culture also was estimated from results of surveillance and market-assurance
      testing in New South Wales. The overall flock-sensitivity of pooled faecal
      culture was 92% (95% CI: 82.4 and 97.4%) compared to 61% (50.5 and 70.9%) for
      serology (assuming that both tests were 100% specific). In low-prevalence flocks
      (estimated prevalence <2%), the flock-sensitivities of pooled faecal culture and
      serology were 82% (57 and 96%) and 33% (19 and 49%), respectively, compared to
      96% (85 and 99.5%) and 85% (72 and 93%), respectively, in higher-prevalence
      flocks (estimated prevalence > or =2%). A Bayesian approach incorporating prior
      knowledge on flock-specificity of pooled culture produced similar estimates and
      probability intervals. These estimates assume conditional independence of the two
      tests, and therefore might have over-estimated the true flock-sensitivities of
      the tests if the flock-sensitivities of pooled faecal culture and serology were
      correlated. The estimated minimum flock-specificity of pooled culture when used
      for surveillance and assurance testing was 99.1% (96.9 and 99.9%). Surveillance
      and assurance programs in Australia are designed to provide a flock-sensitivity
      of 95% for an assumed prevalence of 2%. Pooled faecal culture is performing at
      close to this level--whereas the flock-sensitivity of serology appears to be
      lower than expected, particularly in lower prevalence flocks.

PMID- 11849718
TI  - Risk factors for foot-pad dermatitis in chicken and turkey broilers in France.
AB  - A prospective cohort study was conducted in the Brittany region to identify the
      risk factors related to foot-pad dermatitis (considered an indicator of animal
      well-being) in chicken and turkey broilers reared under commercial conditions.
      Factors related to the shed, equipment, litter management and stocking density
      were recorded; the dependent variable was the prevalence of lesions observed on
      the slaughterhouse chain. Lesions were scored from 0 (no lesion) to 3 (severe
      lesion). Our survey lasted from May 1999 to October 2000. Fifty flocks of chicken
      broilers (15 farms), 27 flocks of female turkey broilers (21 farms) and 41 flocks
      of male turkey broilers (27 farms) were surveyed. In chicken broilers, 10% of
      flocks were of high quality (80% of birds with score 0) and this was related to
      the use of concrete floors with a thin layer of wood shavings. In turkey
      broilers, 48% of female and 46% of male flocks were of bad quality (>10% of birds
      with score 3). A poor fan ventilation system (<150m(3)/h/kg) was a significant
      risk factor. Turkey flocks of high quality were not observed. Stocking density
      had no influence on the prevalence of foot-pad dermatitis. We concluded that it
      is possible under high commercial stocking densities to have flocks with a low
      prevalence of foot-pad dermatitis in chicken broilers, whereas it is not in
      turkey broilers. Hence in chicken broilers, implementing a monitoring system
      based on the observation of foot-pad dermatitis prevalence at slaughter appears
      to be more appropriate than to legislate stocking density. In turkey broilers, it
      would probably be necessary either to reduce the stocking density drastically or
      to investigate new systems of floor drainage.

PMID- 11849719
TI  - Demonstrating disease freedom-combining confidence levels.
AB  - Part of the requirements for demonstrating disease freedom usually will be that
      sufficient testing be done to give a specified confidence of detecting the
      disease if it were present at a specified level. Often, this requirement is
      translated into a fixed testing regime that must be followed (an inflexible
      approach that might not be the most economic or practical solution).A more
      flexible approach is to specify the capabilities of the various tests that can be
      used to detect the disease, and let the party hoping to demonstrate disease
      freedom decide upon the testing regime. The question then arises as to how to
      combine information that can come from a variety of sources over a period of time
      to give an overall level of confidence. Two methods are given. The first, an
      exact method based on multiplying probabilities, would be more appropriate for a
      survey of an area in which no disease is thought to be present. The second method
      (more appropriate for a herd-assurance program within an infected area) is a
      point-based system that takes into account the different sensitivities of the
      methods used to detect disease and the change in prevalence over time. It
      allocates points for each test done proportional to the sensitivity of the test
      and the prevalence at the time of testing.

PMID- 11849720
TI  - Qualitative and quantitative risk assessment for human salmonellosis due to multi
      resistant Salmonella Typhimurium DT104 from consumption of Danish dry-cured pork
      sausages.
AB  - Salmonella Typhimurium DT104 (DT104) is unwanted in products for human
      consumption due to its antibiotic resistance and ability to cause disease. We
      intended to set up an improved monitoring and management program to aid in
      deciding when to use pork contaminated with DT104 for production of sausages
      without jeopardizing consumer safety. We started by carrying out two assessments
      of the risk for human health associated with consumption of sausages produced by:
      (1) Danish pork from average slaughter days; (2) imported pork (IMP) with average
      prevalence of DT104. The assessments showed that, if Salmonella is present, it is
      usually in lower numbers (< or =50 per 400 cm(2) surface). Additionally, during
      processing, the numbers will be reduced by at least 2 log-units. In Danish (DK)
      pork, DT104 constitutes 0.2-1.0% of the Salmonella isolates reported, while in
      imported pork (IMP), 18%. We estimated that out of one million, 25 g servings of
      DK dry-cured sausages, up to two DT104 bacteria could be found in each of 245
      servings. Out of one million servings of 25 g IMP dry-cured sausages, up to two
      DT104 bacteria would occur in each of 19,260 servings.

PMID- 11849721
TI  - The prevalence and dynamics of Salmonella enterica IIIb 61:k:1,5,(7) in sheep
      flocks in Norway.
AB  - Fifty randomly selected sheep flocks from a region in central Norway were sampled
      in December 1999 to determine the flock prevalence of Salmonella enterica
      subspecies diarizonae serovar 61:k:1,5,(7) (S. IIIb 61:k:1,5,(7)). From each
      flock, 15-41 rectal swabs were collected from individual sheep of different age
      groups and examined for S. IIIb 61:k:1,5,(7). Positive flocks were visited again
      in January-April and each time, rectal swabs from the same animals were collected
      and examined for this specific serovar. Seven flocks (14%; 95% CI 6.3-27%) were
      positive for S. IIIb 61:k:1,5,(7) in December; in all, 10 sheep out of the 1233
      (0.8%) were positive at the first sampling. From the seven positive flocks, six,
      five, six, and nine animals were positive in January, February, March, and April,
      respectively. Of the total 21 individual sheep tested positive from January to
      April, 15 were >2 years old (OR(ex)=3.26; 1.1-10.2). Six out of the seven
      positive flocks were large flocks (>117 ewes). Sharing of rams between flocks did
      not seem to be a risk factor for the presence of S. IIIb 61:k:1,5,(7) in a flock.

PMID- 11849722
TI  - Prevalence of a Salmonella subspecies diarizonae in Norwegian sheep herds.
AB  - We studied the prevalence of Salmonella enterica subspecies diarizonae serovar
      61:k:1,5,(7) (S. IIIb 61:k:1,5,(7)) in 133 Norwegian sheep herds from throughout
      the country. We used a nested case-control study to identify major risk factors.
      Two pooled samples (one from lambs and one from adult sheep) were collected from
      each herd from (10 different) abattoirs. The regional prevalence varied from 0 to
      45%, and was more prevalent in adults than in lambs. Sixteen of the 133 herds
      tested positive to S. IIIb 61:k:1,5,(7), and these positive herds were included
      in the questionnaire-based nested case-control part of the study. The controls
      were stratified according to abattoir. Above-median herd size, having white
      crossbreed sheep, and higher annual replacement percentage were the most evident
      risk factors.

PMID- 11849723
TI  - Risk factors for lamb mortality on UK sheep farms.
AB  - Data on neonatal-lamb mortality and flock history were recorded by veterinary
      students working on 108 sheep farms in the UK in Spring 1997. The mean reported
      mortality incidence risk was 10.0% (median 9%; inter-quartile range 5.9-12.3%).
      The outcomes were incidence risks of stillbirth, perinatal (within 24h of birth)
      mortality and postnatal (>24h after birth) mortality. Exposures were screened for
      univariable associations with mortality risk. Logistic binomial multiple
      regressions adjusted for confounding, with farm as a random effect. This study
      has raised hypotheses for management factors associated with lamb mortality that
      warrant further study. Intensive rearing systems appear to be associated with
      increased perinatal and postnatal mortality, although housing ewes at lambing was
      associated with a decreased risk of stillbirth. High perinatal mortality also was
      associated with poor mothering-pen hygiene, flocks that foster more lambs, and
      failure to provide appropriate nursing for sick lambs. Larger flocks, poor ewe
      condition at breeding, and flocks with higher ewe-replacement rates were
      associated with higher postnatal mortality.

PMID- 11849724
TI  - Peste des petits ruminants has been widely present in southern India since, if
      not before, the late 1980s.
AB  - Because previous authorities had suggested that small ruminants were playing a
      part in the dissemination of rinderpest, and a rinderpest-eradication campaign
      was about to begin, it was necessary to make precise virus identifications from a
      number of small-ruminant "rinderpest" outbreaks. When this was done using a
      database created from passive disease reports, we found that epidemics-reportedly
      due to rinderpest-were in fact due to peste des petits ruminants (PPRs). Although
      such cases had been common in India for a number of years, earlier clinical and
      laboratory reports no longer should be regarded as definitive. PPR outbreaks have
      been frequent in recent years. Further, we suggest that PPR is not a recent
      invader of India.

PMID- 11849725
TI  - Comparison of ratio-synthetic, sample-size dependent and EBLUP estimators as
      estimators of food-animal productivity parameters.
AB  - A comparison was made of three small-area sampling methods [two traditional
      design-based methods (ratio-synthetic, sample-size dependent) and one model-based
      method (EBLUP)] in estimation of some cow and sow population productivity
      parameters. Performance was evaluated in estimating both farm-specific mean
      responses and mean animal response over all farms using sample sizes of 100 and
      25. Differences in results obtained with the cow and sow data are discussed in
      terms of the impact of sample size and population size on sampling method. There
      was a tendency for the model-based method to be the best performer in situations
      most likely to be operational when the sampling is done as part of a food-animal
      monitoring scheme. The situations are identified where the sample-size-dependent
      method performed best.

PMID- 11849726
TI  - Analysis of sampling strategies to substantiate freedom from disease in large
      areas.
AB  - In this paper, we deal with the strategies of surveys to substantiate freedom
      from disease for a certain territory. Infection might not be distributed
      homogeneously. So, a relatively high within-herd prevalence might be observed
      while the herd-level prevalence is lower. For this situation, we compare various
      two-stage sample strategies. The calculation of appropriate sample sizes becomes
      quite complicated. The theoretical generalization of the hypergeometric
      distribution by Cameron and Baldock [Prev. Vet. Med. 24 (1998) 1] introduces a
      simple way to evaluate multi-stage sample sizes while regarding real-test
      properties. We demonstrate the theoretical foundations of these calculations.
      These principles open up the possibility of optimizing costs or other relevant
      variables, by choosing the appropriate sample strategy (each of which ensures the
      same alpha-level for the first stage). In addition, we evaluate the statistical
      power of the complete strategies under consideration.Furthermore, we apply our
      theoretical results to a data example of Brucella melitensis. We used the herd
      size situation in Germany, characterized by many small sheep holdings and only a
      few large ones. The consequences of real-test properties on sample sizes and on
      the applicability of several strategies are discussed.

PMID- 11849727
TI  - Cellular function in multicellular system for hormone-secretion:
      electrophysiological aspect of studies on alpha-, beta- and delta-cells of the
      pancreatic islet.
AB  - We review a new method to explore the cellular functions in multicellular system
      by application of the perforated patch-clamp technique to intact pancreatic islet
      of Langerhans. Using this approach, the integrity of the islet is preserved and
      intercellular communication via gap junctions and paracrine processes are
      maintained. By using low-resistance patch electrodes, rapid current responses can
      be monitored under voltage-clamp control. We have applied this methodology to
      answer questions not resolved by patch-clamp experiments on isolated single
      insulin-secreting beta-cells. First, the role of a K(+)-current dependent on
      Ca(2+)-influx for the termination of burst of action potentials in beta-cells
      could be documented. Neither the current, nor the bursting pattern of electrical
      activity is preserved in isolated beta-cells. Second, the conductance of gap
      junctions (approximately 1 nS) between beta-cells was determined. Third,
      electrical properties of glucagon-producing alpha- and somatostatin-secreting
      delta-cells and the different mechanisms for glucose-sensing in these cells could
      be explored. The findings emanating from these experiments may have implications
      for neuroscience research such as the mechanism of oscillatory electrical
      activity in general and processes involved in the glucose-sensing in some
      neurons, which response to changes of blood glucose concentration.

PMID- 11849728
TI  - Increased intra-articular concentration of bradykinin in the temporomandibular
      joint changes the sensitivity of muscle spindles in dorsal neck muscles in the
      cat.
AB  - The aim of the present study was to investigate to what extent activation of
      bradykinin-sensitive nerve endings of the temporomandibular joint (TMJ) might
      induce changes in the muscle spindles output from neck muscles through reflex
      effects on cervical fusimotor neurones. To this end, 26 muscle spindle afferents
      (MSAs) emanating from the trapezius and splenius muscles of the anaesthetised cat
      (alpha-chloralose, initial dosage 60 mg/kg) were recorded during injection of
      Bradykinin (BK) (12.5-50 microg/ml) in the ipsilateral TMJ. Fifteen (58%) MSAs
      exhibited statistically significant fusimotor effects to injection of BK into the
      TMJ. Of the 15, ten MSAs showed a response related to activation of static
      fusimotor neurones, three MSAs showed a response related to an activation of both
      static and dynamic fusimotor neurones and two MSAs showed a inhibition of both
      static and dynamic fusimotor neurones. The control experiments suggests that the
      effects observed were due to activation of BK sensitive nerve endings in the TMJ.
      It seems possible that the reflex connections between TMJ nociceptors and the
      fusimotor-muscle spindle system of dorsal neck muscles might be involved in the
      pathophysiological mechanisms responsible for the sensory-motor disturbances in
      the neck region often found on patients with temporomandibular disorders.

PMID- 11849729
TI  - Properties of voltage dependent potassium currents in acutely isolated rat
      oculomotor neurons.
AB  - Voltage-dependent potassium currents in oculomotor neurons (OMNs) were studied
      with whole-cell patch clamp recordings. Fast inactivating outward currents
      (I(fast)) had half activation voltage (Vh) of -37.1 mV with slope factor (Vc) of
      10.9 mV. I(fast) had half inactivation voltage (Vh) of -66.5 mV and Vc of 11.4
      mV. I(fast) decayed with a time constant(tau) of 5.1 ms at +10 mV. I(fast) were
      sensitive to 4-aminopyridine, showing 50% inhibitory concentration (IC(50)) of
      0.97 mM. Slowly inactivating outward currents (I(slow)) had two components. The
      low-concentration-TEA-sensitive currents had Vh of -3.7 mV with Vc of 9.7 mV in
      activation and had Vh of -54.7 mV with Vc of 23.8 mV in inactivation. The
      persistent currents had Vh of 7.4 mV and Vc of 11.8 mV in activation and Vh of 
      54.4 mV and Vc of 21.2 mV in inactivation. Decay of I(slow) (+10 mV) followed a
      double exponential time course (tau 215, 1165.6 ms). Low-concentration-TEA
      sensitive currents were blocked completely by tetraethylammonium (TEA) of 3 mM
      with an IC(50) of 1.52 mM. Higher concentrations (3-20 mM) of TEA blocked the
      persistent currents, with an IC(50) of 6.9 mM.

PMID- 11849730
TI  - Effects of nocturnal bright light on saliva melatonin, core body temperature and
      sleep propensity rhythms in human subjects.
AB  - Nine healthy male volunteers (mean age of 24) participated in two experimental
      sessions of random crossover design: a bright light (5000 lux for 5 h from 00:00
      to 05:00 h) session and a dim light (10 lux for 5 h from 00:00 to 05:00 h)
      session. Subsequently participants entered an ultra-short sleep-wake schedule for
      26 h, in which a sleep-wake cycle consisting of 10-min sleep EEG recording on a
      bed and 20-min resting awake on a semi-upright chair were repeated. Saliva
      melatonin level and core body temperature was measured throughout the experiment.
      Bright light significantly delayed rhythms of melatonin secretion (01:58 h), core
      body temperature (01:12 h) and sleep propensity (02:00 h), compared as dim light
      session. Significant positive correlation was found between bright light-induced
      phase change in core body temperature and that in sleep propensity rhythm. Light
      induced melatonin suppression significantly positively correlated with the phase
      change in core body temperature and that in sleep propensity rhythm. Assuming
      that light-induced melatonin suppression represents an acute impact of light on
      the circadian pacemaker, our results suggest that such an impact may be directly
      reflected in phase changes of sleep propensity and core body temperature rhythms
      rather than in melatonin rhythm.

PMID- 11849731
TI  - Cell dynamics of calretinin-immunoreactive neurons in the rostral migratory
      stream after ibotenate-induced lesions in the forebrain.
AB  - It is now apparent that adult neurogenesis is taking place during life in the
      olfactory bulb (OB) of the rodent brain. In the olfactory nervous system, the
      precursor cells of the subventricular zone are known to continually proliferate,
      migrate through the rostral migratory stream (RMS) and differentiate into the
      bulbar neurons. The RMS, consisting of heterogeneous cell populations of the
      neural and neuronal precursor cells, is the unique forebrain structure that
      provides a long-distance migratory route for the precursor cells. The present
      study was undertaken to examine whether neuronal regeneration, focusing on
      calretinin-immunoreactive (+) cells, may proceed in the RMS following lesions
      induced by an excitotoxin. Two days after ibotenate injections, massive
      degeneration of calretinin (+) cells occurred in the RMS and its adjacent
      forebrains. Thereafter, calretinin (+) cells gradually increased in the RMS and
      reached above their control value 2 weeks after ibotenate injections. Removal of
      the OB also produced a marked increase in calretinin (+) cells in the RMS.
      Autoradiographic experiments using (3)H-thymidine showed that calretinin (+)
      cells were continually generated in the RMS and underwent neuronal turnover
      within 8 weeks in a normal condition. The results indicate that, in terms of
      calretinin (+) cells, neuronal differentiation and replacement is continually
      taking place within the RMS, and that the RMS is capable of repopulating those
      cells which were injured by ibotenate.

PMID- 11849732
TI  - Axonal transport of puromycin-sensitive aminopeptidase in rat sciatic nerves.
AB  - Axonal transport of puromycin-sensitive aminopeptidase (PSA), a putative
      neuropeptide degrading-enzyme which removes amino acid residues from the amino
      terminal of neuropeptides, was examined in the proximal, middle, and distal
      segments of rat sciatic nerves using a double-ligation technique. The soluble
      fraction of each segment was partially purified by MonoQ column chromatography,
      and showed two peaks of aminopeptidase activity. One of the aminopeptidases was
      PSA. At 48 h after the ligations, a significant amount of the axonal transport of
      PSA activity was found in the proximal segment. Western blot analysis of the
      segments also showed that immunoreactive PSA in the proximal segment was 2.1-fold
      higher than that in the middle segment. Furthermore, the immunohistochemical
      analysis of the segments showed an increase of the immunoreactive PSA in the
      proximal segment in comparison with the enzyme in the distal segment, indicating
      that PSA is mainly transported by anterograde axonal flow. These results suggest
      that PSA plays a role in the metabolism of neuropeptides in nerve terminals or
      synaptic clefts.

PMID- 11849733
TI  - Loss of adaptability of horizontal optokinetic response eye movements in mGluR1
      knockout mice.
AB  - Metabotropic glutamate receptor subtype 1 (mGluR1) plays an essential role in the
      cerebellar long-term depression (LTD). We examined the dynamic characteristics
      and adaptability of horizontal vestibulo-ocular reflex (HVOR) and optokinetic
      response (HOKR) eye movements in mGluR1 knockout mice. A mild difference was seen
      in the HOKR/HVOR dynamics between the wild-type and mGluR1(-/-) mice. Exposure to
      1 h of sustained screen oscillation, which induced HOKR adaptation in wild-type
      mice, induced no change in mutant mice. These results suggest that the mGluR1
      plays an essential role in the adaptation of HOKR, and LTD underlies the
      adaptation of ocular reflexes.

PMID- 11849734
TI  - The role of TNF-alpha in amygdala kindled rats.
AB  - In the present study, the interaction between epileptogenesis and the immune
      system were studied in a kindling model. First, the effects of a single
      administration of TNF-alpha (5.0 microg/kg, i.p.) on seizure and EEG activity
      were investigated in amygdala-kindled rats. TNF-alpha treated rats showed more
      prolonged epileptiformic discharges than control rats. TNF-alpha also induced a
      decrease in the power of delta band and an increase in theta and alpha activity.
      In addition, a marked increase in the power of beta and gamma band was observed.
      The EEG changes were most numerous in the frontal cortex and amygdala. All
      effects were registered 24 h after TNF-alpha administration. Finally, electrical
      stimulation enhanced the level of TNF-alpha in blood serum from 1.9 +/- 1.5 to
      12.7 +/- 3.8 pg/ml and in brain tissue 56.8 +/- 6.0 to 109.2 +/- 6.0 pg/mg, as
      was determined via the ELISA method. It can be concluded that there is a mutual
      facilitative interaction of both epileptogenic and cytokine-derived mechanisms on
      this type of seizure. The changes in the power spectrum of the EEG after TNF
      alpha might contribute to intensify thalamic-derived facilitation of epileptic
      discharge in cortical structures.

PMID- 11849735
TI  - Improvement of a two-stage carcinogenesis model to detect modifying effects of
      endocrine disrupting chemicals on thyroid carcinogenesis in rats.
AB  - In order to improve the sensitivity of our previously established thyroid
      carcinogenesis model and to clarify whether endocrine disrupting chemicals with
      weak estrogenic activity have any modifying effects on the development of thyroid
      proliferative lesions, 6-week-old female castrated F344 rats were first given a
      single subcutaneous injection of 2000 mg/kg body weight of N-bis(2
      hydroxypropyl)nitrosamine. From 1 week later, they received diets with: no
      supplement (basal diet (BD) group); cholesterol pellets containing 0.5 mg 17 beta
      estradiol 3-benzoate (EB); or diet admixed with 1000 ppm methoxychlor (MXC) or
      10,000 ppm bisphenol A (BPA) for 20 weeks. Furthermore, additional groups were
      administered 200 ppm sulfadimethoxine (SDM) in the drinking water simultaneously
      with the BD, EB, MXC or BPA treatments. Thyroid follicular cell hyperplasias,
      adenomas and/or carcinomas were induced only in the EB+SDM group, the incidences
      of non-malignant lesions being significantly increased, as compared with the
      BD+SDM group values. Furthermore, the serum level of thyroid stimulating hormone
      (TSH) was significantly increased in this group. No significant variation in
      quantitative values for thyroid proliferative lesions or TSH levels were observed
      in the other treated groups. The results of the present study convincingly
      indicate that EB, with strong estrogenic activity, but not MXC and BPA, with weak
      estrogenic activities, exerts promoting effects on thyroid carcinogenesis in
      rats. The present modified rat two-stage thyroid carcinogenesis model appears to
      have advantages over our previous model for screening purposes.

PMID- 11849736
TI  - The effect of pentachlorophenol on DNA adduct formation in p53 wild-type and
      knockout mice exposed to benzo[a]pyrene.
AB  - Previous studies have shown that pentachlorophenol (PCP) has both potentiative
      and antagonistic effects on the genotoxicity of benzo[a]pyrene (B[a]P). It has
      been suggested that these effects are due to inhibition and/or induction of
      enzymes involved in the biotransformation of B[a]P [Carcinogenesis 16 (1995)
      2643]. However, B[a]P [J. Biol. Chem. 274 (1999) 35240] and a metabolite of PCP,
      tetrachlorohydroquinone (TCHQ) [Chem. Biol. Interact. 105 (1997) 1], induce p53
      protein synthesis in vitro. To investigate this effect further, C57BL/6Tac
      trp53+/+ (wild-type, WT) and C57BL/6Tac trp53-/- (knockout, KO) mice were exposed
      to 55 microg B[a]P/g BW alone or in combination with 25 microg/g PCP. Hepatic and
      lung DNA were analyzed for the major B[a]P DNA adduct, 7R,8S,9S-trihydroxy-10R
      (N2-2'-deoxyguanosyl)-7,8,9,10-tetrahydro-B[a]P (BPDE-N2G) and other minor
      adducts using the 32P-postlabeling assay. BPDE-N2G adducts were detected in all
      animals exposed to B[a]P. Similar adduct levels were observed in WT mice exposed
      to 55 microg/g B[a]P compared with KO mice exposed to B[a]P alone or in
      combination with PCP. Interestingly, hepatic and lung BPDE-N2G adducts were
      decreased in WT mice exposed to B[a]P with PCP (P<0.05). Total DNA adducts in the
      liver (P<0.05) were also decreased in WT mice exposed to B[a]P and PCP. Total DNA
      adducts in either hepatic or lung DNA isolated from KO mice were not different in
      mice treated with PCP and B[a]P. These results suggest that the decrease in BPDE
      N2G adducts observed in WT mice may be a result of p53 accumulation or induction
      of repair pathways in response to damage induced by PCP.

PMID- 11849737
TI  - Promoting effects of combined antioxidant and sodium nitrite treatment on
      forestomach carcinogenesis in rats after initiation with N-methyl-N'-nitro-N
      nitrosoguanidine.
AB  - The effects of sodium nitrite (NaNO2), in combination with one of three
      antioxidants, tert-butylhydroquinone (TBHQ), alpha-tocopherol (alpha-Toc) and
      propyl gallate (PG), on N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) stomach
      carcinogenesis were investigated in F344 rats. Groups of 15 male rats were
      treated with an intragastric dose of 150 mg/kg body weight of MNNG, and starting
      1 week later, were treated with 0.5% TBHQ, 1% alpha-Toc, 1% PG or basal diet with
      or without 0.2% NaNO2 in their drinking water until they were killed at the end
      of week 36. Macroscopically, in MNNG-treated animals, combined administration of
      alpha-Toc or PG with NaNO2 significantly increased the areas and numbers of
      forestomach nodules as compared with the respective antioxidant alone values.
      Microscopically, in MNNG-treated animals, treatment with TBHQ significantly
      increased the incidence and multiplicity of forestomach papillomas as compared
      with basal diet alone value. Combined administration of alpha-Toc with NaNO2
      significantly raised the multiplicity of forestomach papillomas, with a tendency
      to elevation in the incidence as compared with the group given alpha-Toc alone.
      Incidences of forestomach moderate and/or severe hyperplasias were significantly
      higher in the TBHQ or PG plus NaNO2 groups than in the single compound groups. In
      rats without MNNG treatment, combined treatment of antioxidants with NaNO2
      significantly increased the incidences of mild or moderate hyperplasia. In the
      glandular stomach, although the incidence of atypical hyperplasia showed a non
      significant tendency for decrease with TBHQ treatment, additional administration
      of NaNO2 caused significant increase. These results indicate that co
      administration of NaNO2 with alpha-Toc, TBHQ or PG and particularly the first,
      promotes forestomach carcinogenesis. Concurrent alpha-Toc, TBHQ or PG treatment
      with NaNO2 is likely to induce forestomach tumors in the long term.

PMID- 11849738
TI  - Induction of CYP1A1 and CYP1A2 expressions by prototypic and atypical inducers in
      the human lung.
AB  - The inducibility of cytochrome P4501A1 gene (CYP1A1) expression was examined in
      human lung samples from 27 subjects, using an explant culture system and semi
      quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analysis.
      CYP1A1 transcripts were present in all of the lung specimens and were induced by
      the prototypic inducers 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and
      benzo[a]pyrene (B[a]P), and by the atypical inducers pyridine, nicotine, and
      omeprazole. 2-Hydroxypyridine was a better inducer than pyridine, implicating
      metabolites in CYP1A1 induction by the parent compound. The prototypical inducers
      were the most effective inducers in many samples but were ineffective in some
      samples in which the atypical compounds were effective inducers. Cytochrome
      P4501A2 (CYP1A2) transcripts were also detected in most of the lung specimens and
      were inducible in some specimens. The results show the suitability of the explant
      culture system for examining the inducibility of human pulmonary CYP1A1 and
      CYP1A2, indicate the heterogeneity in individual sensitivity to the induction,
      and underscore the need to include atypical inducers in studies of CYP1A
      inducibility in humans.

PMID- 11849739
TI  - DNA damage induced by hypochlorite and hypobromite with reference to inflammation
      associated carcinogenesis.
AB  - Hypohalites (OCl-, OBr-) are formed at inflammation sites as antimicrobial
      agents. OCl- is also used for the disinfection of water supplies and the
      association of drinking chlorinated water with cancer risk is pointed out. In
      this study, OCl- itself induced 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG)
      formation, while OBr- damaged DNA only when glutathione (GSH) was added. OCl-
      caused oxidative DNA damage more efficiently than OBr-/GSH. In experiment with
      32P-labeled DNA fragments, OCl- strongly caused piperidine-labile sites at
      guanine residues than piperidine-inert 8-oxodG, whereas OBr-/GSH caused no
      piperidine-labile sites. Endogenous OCl- may play a role in genotoxicity close to
      the site of inflammation.

PMID- 11849740
TI  - Assessment of the quality and frequency of mutations occurrence in PTEN gene in
      endometrial carcinomas and hyperplasias.
AB  - The quality and frequency of mutations in PTEN gene were assessed in 59
      carcinomas and 6 hyperplasias of the endometrium in women. Screening for
      mutations was done in all exons of PTEN gene by the PCR-SSCP analysis and DNA
      sequencing. Results were correlated with histological status and clinical
      features of endometrial carcinomas. In 45.8% (27/59) of carcinomas, 36 somatic
      mutations were detected in PTEN gene. In seven carcinomas, two mutations and in
      one carcinoma three mutations coexisted simultaneously. Moreover in 33.3% (2/6)
      of hyperplasia cases mutations were shown. Most identified mutations (57.9%) were
      present in exons 5 and 8, less frequently in exons 2 (15.8%) and 7 (13.2%) and
      they were least frequent in exons 1 and 3 (5.3% each). No mutations were found in
      exons 4, 6 and 9. Of all identified mutations, 73.7% of those resulting in
      truncated protein were present due to deletions, insertions and nonsense
      mutations. Missense mutations accounted for 13.2% of mutations and they were
      present only in exon 5. One point mutation (2.5%) was in intronic splice site.
      The remaining 10.5% of mutations were neutral polymorphisms. No statistically
      significant correlation were found between the frequency of PTEN gene mutations
      and the clinical stage of endometrial carcinomas. However, evident statistically
      significant, reverse correlation were observed between the frequency of mutations
      and the grade of morphological differentiation of the diseases (chi(2)=7.2393,
      alpha=0.0071). In conclusion, our data support the view that PTEN gene mutations
      are frequent events involved in development of endometrial carcinomas in women.

PMID- 11849741
TI  - Protective effect of L-carnosine against 12-O-tetradecanoylphorbol-13-acetate- or
      hydrogen peroxide-induced apoptosis on v-myc transformed rat liver epithelial
      cells.
AB  - Apoptotic processes have been associated with cancer and neurodegenerative
      diseases such as Alzheimer's disease, Parkinson's disease etc. beta-Alanyl-L
      histidine (L-carnosine), occurring abundantly in skeletal muscles has been
      suggested to possess antioxidative activity. We investigated whether L-carnosine
      prevents 12-O-tetradecanoylphorbol-13-acetate (TPA)- or hydrogen peroxide (H2O2)
      induced apoptosis involving mitochondria in the v-myc transformed rat liver
      epithelial cells (WB-myc cells). L-Carnosine prevented both TPA- and H2O2-induced
      DNA fragmentation, the loss of mitochondrial membrane potentials and blocked the
      release of cytochrome c into cytosol. Subsequently, the cleavages of poly (ADP
      ribose) polymerase were significantly reduced in L-carnosine-treated cells.
      However, western blotting analysis revealed that p53 protein level did not change
      for 12h after TPA- and H2O2-treatment. Therefore, these results suggested that L
      carnosine, an antioxidant, protected both H2O2- and TPA-induced apoptosis through
      mitochondrial pathways.

PMID- 11849742
TI  - Enhancement of hyperthermia-induced apoptosis by non-thermal effects of
      ultrasound.
AB  - To determine the effect of ultrasound on hyperthermia-induced apoptosis, we
      exposed U937 cells (in air-saturated suspension) to continuous 1 MHz ultrasound
      at intensities 0.5 or 1.0 W/cm(2), considered non-thermal and sub-threshold for
      inertial cavitation, while at 44.0 degrees C for 10 min. We found that 0.5
      W/cm(2), in combination with hyperthermia, synergistically induced apoptosis. On
      the other hand, 1.0 W/cm(2) in combination with hyperthermia showed an augmented
      instant cell lysis but no significant change in the ratio of apoptosis. This
      result might be useful when apoptosis induction is desired over instant cell
      killing in cancer therapy.

PMID- 11849743
TI  - Manganese superoxide dismutase genotypes and asbestos-associated pulmonary
      disorders.
AB  - Manganese superoxide dismutase (MnSOD) activity is highly elevated in the
      biopsies of human asbestos-associated malignant mesothelioma. We therefore
      examined if polymorphism in the mitochondrial targeting sequence of the MnSOD
      gene modified individual susceptibility to this malignancy or related asbestos
      associated pulmonary disorders. The study population consisted of 124 male
      Finnish asbestos insulators who were all classified as having been exposed to
      high levels of asbestos; 63 of the workers had no pulmonary disorders and 61
      either had malignant mesothelioma or the non-malignant pulmonary disorders
      asbestosis and/or pleural plaques. No significant associations were found between
      the MnSOD genotypes and these ill-health. This study therefore suggest no major
      modifying role for the MnSOD polymorphism in development of asbestos-associated
      pulmonary disorders.

PMID- 11849744
TI  - Loss of heterozygosity on chromosome 11 in esophageal squamous cell carcinomas.
AB  - Esophageal cancer (ESC) is an important cancer worldwide. Chromosome 11 plays an
      important role in the development of several human cancers. In this study, 19
      polymorphic microsatellite markers spanning the whole chromosome 11 were used to
      screen for loss of heterozygosity (LOH) in 38 primary esophageal squamous cell
      carcinomas. Thirty-three of 38 samples (86.8%) showed LOH at one or more loci.
      High frequencies (51.9-61.1%) of allelic loss were observed at D11S1338,
      D11S2000, D11S1990, and D11S1647 loci, in two chromosomal regions, 11p15.5 and
      11q22.3. The results of this study suggest the presence of putative tumor
      suppressor genes in these two regions on chromosome 11 related to ESC.

PMID- 11849745
TI  - Cytogenetic analysis of infantile neuroblastomas by comparative genomic
      hybridization.
AB  - Neuroblastomas are heterogeneous tumors. Their clinical behavior varies from
      spontaneous regression to malignant progression. To investigate the cytogenetic
      heterogeneity of infantile neuroblastomas, we employed comparative genomic
      hybridization (CGH). To characterize chromosomal imbalances in 35 infantile
      neuroblastomas, we performed CGH and compared our results with those of other
      clinical and biological studies. The most frequent genetic imbalances were found
      in chromosome 17 (43%), including whole chromosome 17 gains in eight patients
      (23%) and 17q gains in seven patients (20%). A 1p loss and a 2p gain were
      detected in six patients each (17%). Losses of 11q and 14q were detected in two
      patients (6%) and one (3%) patient, respectively. The number of gains of 17q were
      significantly higher in DNA diploid tumors than in aneuploid tumors (P=0.006).
      Conversely, whole chromosome 17 gains were not found in DNA diploid tumors and/or
      MYCN amplification. Interestingly, nine of 17 tumors that were histologically
      evaluated showed a spontaneous regression and did not demonstrate any partial
      chromosomal abnormalities (i.e. 17q gain, 1p loss, 2p gain, 11q loss and 14q
      loss). These results suggest that a gene on chromosome 17q is associated with
      neuroblastoma progression. Finally, our observations indicate that the
      chromosomal imbalances observed in infantile neuroblastomas are different from
      those observed in older patients.

PMID- 11849746
TI  - Variations in gene expression patterns correlated with phenotype of F-11 tumor
      cells whose expression of GD3-synthase is suppressed.
AB  - Alteration in ganglioside composition in F-11 cells by suppression of GD3
      synthase gene expression resulted in greatly reduced tumor growth and metastasis
      when the cells were injected into nude mice. To identify genes whose expression
      is correlated with the decreased level of ganglioside GD3, we analyzed gene
      expression profiles of the GD3-suppressed F-11 cells and the control F-11 cells
      using DNA microarrays. We identified a set of GD3-related genes, most of which
      are involved in tumor growth and development. The genes that define the
      proliferation-transformation signature are down-regulated, such as creatine
      kinase-B (CKB), upstream stimulation factor 1 (USF-1), type II cAMP-dependent
      protein kinase regulatory subunit (RII PKA), and tyrosine hydroxylase (TH). On
      the other hand, the genes that define the differentiation-reverse transformation
      signature are up-regulated, including p160 myb-binding protein (P160), brain
      factor-2, insulin-like growth factor-binding protein (IGFBP), and
      growth/differentiation factor 11. Transcriptional levels of the genes that showed
      the most distinct GD3-related expression change were validated by reverse
      transcription-polymerase chain reaction (RT-PCR). Defining GD3-related genes may
      lead to identification of clinically relevant therapeutics and to understanding
      of the mechanism(s) by which ganglioside GD3 affects tumor growth and metastasis.

PMID- 11849747
TI  - Significant correlation between expression of heat shock proteins 27, 70 and
      lymphocyte infiltration in esophageal squamous cell carcinoma.
AB  - The objective of this study was to clarify the clinicopathologic and prognostic
      significance of heat shock proteins (HSP) 27 and 70 expression in esophageal
      squamous cell carcinoma (SCC). Immunohistochemical staining for HSPs 27 and 70
      was performed on surgical specimens obtained from 62 patients with esophageal
      SCC. The expression of both HSPs 27 and 70 correlated inversely with depth of
      invasion (P<0.05) and pathologic stage (P<0.05), and correlated positively with
      lymphocyte infiltration (P<0.05). Reduction of HSP 70 expression was
      significantly correlated with poor prognosis (P<0.05). Patients with HSP 27
      negative tumors tended to have a poor prognosis compared with patients with HSP
      27-positive tumors. The present findings suggest that HSPs 27 and 70 are
      significant prognostic factors for esophageal SCC.

PMID- 11849748
TI  - Expression of bile duct-type cytokeratin in hepatocellular carcinoma in patients
      with hepatitis C virus and prior hepatitis B virus infection.
AB  - The clinicopathologic findings in patients with hepatitis C virus (HCV)-related
      hepatocellular carcinoma (HCC) positive for biliary markers, those related to the
      hepatic progenitor cells, were investigated. Cytokeratin (CK) 19 was reactive for
      HCCs only in patients with prior hepatitis B virus (HBV) infection. The
      proportions of patients with prior HBV infection and poorly differentiated HCC
      were significantly higher among those with CK 19-positive HCC than among those
      with CK 19-negative HCC. Some HCCs develop from the hepatic progenitor cells in
      patients with HCV infection and prior HBV infection, which may affect the
      clinicopathologic findings of HCV-related HCCs.

PMID- 11849749
TI  - Phase advance of sleep and temperature circadian rhythms in the middle years of
      life in humans.
AB  - Age-related changes in sleep may be linked to modifications in the circadian
      timing system. This study compared sleep patterns and unmasked circadian
      temperature parameters between a group of young subjects and a group of middle
      aged subjects. Habitual bedtime and waketime were earlier in the middle-aged than
      in the young. In addition, middle-aged subjects reported a greater orientation
      toward morningness and they showed an earlier phase of temperature rhythm. No
      differences were found in amplitude of temperature rhythm or in habitual phase
      angle between sleep and the temperature rhythm. In conclusion, a phase advance of
      sleep and temperature circadian rhythm is already apparent in people in their
      forties and fifties. These changes precede modifications in amplitude or in
      habitual phase angle.

PMID- 11849750
TI  - Asymmetries of prefrontal cortex in human episodic memory: effects of
      transcranial magnetic stimulation on learning abstract patterns.
AB  - Functional neuroimaging suggests asymmetries of memory encoding and retrieval in
      the prefrontal lobes, but different hypotheses have been presented concerning the
      nature of prefrontal hemispheric specialization. We studied an associative memory
      task involving pairs of Kanji (Chinese) pictographs and unfamiliar abstract
      patterns. Subjects were ten Japanese adults fluent in Kanji, so only the abstract
      patterns represented novel material. During encoding, transcranial magnetic
      stimulation (TMS) was applied over the left and right dorsolateral prefrontal
      cortex (DLPFC). A significant (P<0.05) reduction in subsequent recall of new
      associations was seen only with TMS over the right DLPFC. This result suggests
      that the right DLPFC contributes to encoding of visual-object associations, and
      is consistent with a material-specific rather than a process-specific model of
      mnemonic function in DLPFC.

PMID- 11849751
TI  - Differential tyrosine kinase C mRNA distribution in extensor digitorum longus and
      soleus motoneurons in adult rats: effect of axotomy and neurotrophin-3 treatment.
AB  - Delivery of neurotrophin-3 (NT-3) to severed sciatic nerves results in specific
      normalization of atrophied fast 2b gastrocnemius muscle fibres, and promotes
      preferential neuromuscular junction maturation of fast extensor digitorum longus
      (EDL). To investigate the selective influence on fast muscle reinnervation due to
      NT-3 delivery, we analyzed tyrosine kinase C (trkC) mRNA differential expression
      in EDL and slow soleus motor pools of unoperated rats and at 1-week post-axotomy.
      Motoneurons (Mns) were identified using retrograde tracers. TrkC mRNA
      quantification was estimated by silver grain counting. TrkC mRNA expression was
      higher in EDL than in soleus Mns in unoperated rats. Axotomy decreased trkC mRNA
      expression only in EDL Mns, this downregulation being prevented by NT-3. These
      results suggest that differential expression of trkC receptor is the
      morphological correlate of the preferential effect of NT-3 upon EDL Mns.

PMID- 11849752
TI  - Rhythmic expression of ROR beta mRNA in the mice suprachiasmatic nucleus.
AB  - The expression of the brain rich orphan nuclear receptor ROR beta (retinoid
      related orphan receptor beta) was investigated in the mouse brain by in situ
      hybridization using antisense cRNA probe. Positive ROR beta mRNA signals were
      detected in various parts of the brain with high expression in the
      suprachiasmatic nucleus (SCN). In the SCN, ROR beta mRNA signals showed a peak at
      early daytime (ZT/CT4) and a trough at early nighttime (ZT/CT16) in both light
      dark and constant dark conditions. Light exposure at subjective night did not
      alter the expression level. These findings suggest that ROR beta is a new member
      of a transcription factor possibly related to the circadian pacemaking system.

PMID- 11849753
TI  - Macrophage-related demyelination in peripheral nerves of mice deficient in the
      gap junction protein connexin 32.
AB  - Mice deficient in the gap junction protein connexin 32 (Cx32) develop a slowly
      progressing demyelinating neuropathy, with enlarged periaxonal collars, abnormal
      non-compacted myelin domains and axonal sprouts. These mice serve as a model for
      the X-linked form of inherited demyelinating neuropathies in humans. Based on our
      previous findings that macrophages are involved in demyelination in other myelin
      mutants (i.e. mice heterozygously deficient in P0), we considered the possibility
      that macrophages might be also mediators of demyelination in Cx32-deficient mice.
      Indeed, we detected an age-related increase in the number of macrophages in
      demyelinating nerves of Cx32-deficient mice. In addition, immunoelectron
      microscopy revealed macrophages in an apposition to degenerating myelin
      reminiscent of a macrophage-mediated demyelinating neuropathy. We conclude that
      involvement of macrophages might be a widespread phenomenon in genetically
      determined demyelination.

PMID- 11849754
TI  - Unique immunomodulation by electro-acupuncture in humans possibly via stimulation
      of the autonomic nervous system.
AB  - Cumulative evidence suggests that immunologic responses are under the regulation
      of the autonomic nervous system. Since acupuncture has recently been reported to
      modulate the autonomic nervous system, we investigated the possibility that
      acupuncture eventually modulates the immune system. In the present study, electro
      acupuncture was applied in young volunteer subjects. As for the proportions of
      granulocytes and lymphocytes in the blood, there were three groups: (1)
      granulocytosis and lymphocytopenia; (2) granulocytopenia and lymphocytosis; and
      (3) normal pattern. Interestingly, with the administration of acupuncture, the
      status of subjects with relatively low levels of granulocytes and high levels of
      lymphocytes shifted to Group 1, whereas that of subjects with high levels of
      granulocytes and low levels of lymphocytes shifted to Group 2. In other words,
      acupuncture tended to normalize the pattern of leukocytes. We confirmed that
      acupuncture induced parasympathetic nerve stimulation, resulting in a decrease in
      the heart rate. These results suggest possible mechanisms underlying how
      acupuncture ameliorates the condition of patients with many chronic diseases.

PMID- 11849755
TI  - Age-dependent association between butyrylcholinesterase K-variant and Alzheimer
      disease-related neuropathology in human brains.
AB  - The association between the K-variant of the butyrylcholinesterase gene (BCHE-K)
      and Alzheimer disease (AD) or AD-related neuropathology has been reported to date
      with conflicting results. Here, we determined in a sample of 521 cases the
      severity of AD-related neuropathology and the polymorphisms of both BCHE-K and
      apolipoprotein E (ApoE). Histopathologically, all brains were classified
      according to procedures permitting differentiation of the evolutionary stages of
      neurofibrillary tangles (NFTs) and amyloid-beta-protein deposition (A beta
      deposits). The results show that the association between BCHE-K and AD-related
      neuropathology only was limited to homozygotes for the K allele (P=0.036 for
      NFTs, and P=0.045 for A beta-deposits) at ages > or = 70 years but not 50-69
      years. Furthermore, no interaction was apparent between BCHE-K and ApoE.

PMID- 11849756
TI  - Mitogen-activated protein kinase kinase 7 is activated during low potassium
      induced apoptosis in rat cerebellar granule neurons.
AB  - A stress-activated protein kinase pathway comprising mitogen-activated protein
      kinase kinases (MKKs), c-Jun N-terminal kinase (JNK) and the transcription factor
      c-Jun is implicated in neuronal apoptosis. Using an immune-complex kinase assay,
      we measured the activation of MKK4 and MKK7 in low potassium (LK)-induced
      apoptosis of rat cerebellar granule neurons (CGN). MKK7, but not MKK4, was
      activated within the first 4-6 h in four independent sets of 14-h CGN apoptosis
      time-courses. CEP-1347 (500 nM), an mixed-lineage kinase 3 inhibitor, prevented
      MKK7 activation and cell death following exposure of CGN cultures to LK-induced
      apoptosis. Western blot analysis revealed that levels of phosphorylated c-Jun
      were elevated between 30 min and 10 h of CGN apoptosis, temporally consistent
      with MKK7 activation. These data suggest that MKK7 is responsible for activating
      the JNK pathway during LK-induced CGN apoptosis.

PMID- 11849757
TI  - ATP-dependent potassium channel mediates neuroprotection by chemical
      preconditioning with 3-nitropropionic acid in gerbil hippocampus.
AB  - Chemical preconditioning with low dose of 3-nitropropionic acid (3-NPA) prolongs
      the latency to hypoxic depolarization (HD), which triggers cell death, and also
      restores the synaptic transmission which disappears during hypoxia in gerbil
      hippocampal slices. Here we show that these neuroprotective effects are mediated
      by the activation of K(ATP) channels. Diazoxide, a K(ATP) channel opener,
      prolonged the latency to HD dose-dependently to the same extent as that of the
      chemical preconditioning with 3-NPA. Glibenclamide, a K(ATP) channel blocker,
      abrogated the prolongation of HD with 3-NPA. The hypoxic tolerance of synaptic
      transmission with 3-NPA was also abolished by glibenclamide. Diazoxide also
      induced the hypoxic tolerance of synaptic transmission. Theses results suggest
      that K(ATP) channel is involved in the neuroprotection afforded by the chemical
      preconditioning.

PMID- 11849758
TI  - A direct projection from the cerebellum to the telencephalon in the goldfish,
      Carassius auratus.
AB  - Recent studies showed that the cerebellum is involved in cognitive functions
      previously thought to be located in the telencephalon only. Various indirect
      connections between telencephalon and cerebellum are long known and may be the
      basis for the interaction of these two brain areas. By means of biotinylated
      dextran amine injections into the telencephalon and cerebellum in the goldfish,
      Carassius auratus, we found a direct projection from the valvula cerebelli to the
      telencephalon. Together with other studies in fish, birds, and mammals, these
      data suggest that direct connections between cerebellum and telencephalon are
      more common than previously thought and may contribute to the integration of
      telencephalic and cerebellar functions.

PMID- 11849759
TI  - Leptin receptor expression in nodose ganglion cells projecting to the rat gastric
      fundus.
AB  - Recent studies suggest that in addition to adipocytes the chief cells of the
      gastric fundic mucosa are a site of leptin production. In order to assess the
      possible role of vagal afferent neurons in transmitting leptin signals from the
      stomach to the brain, leptin receptor (OB-R) expression was investigated in rat
      nodose ganglion cells and their projection to the stomach determined by
      retrograde tracing. Reverse transcription-polymerase chain reaction combined with
      laser-assisted cell picking revealed that large and small diameter neurons
      express both the long (OB-Rb) and short (OB-Ra) splice variants of the OB-R. OB-R
      like immunoreactivity was detected in the perikarya of approximately 8% of nodose
      ganglion neurons. Tracing studies revealed that a significant proportion (15%) of
      the immunopositive neurons projected to the gastric fundus. These findings
      suggest that leptin may use a neural route to relay its message from peripheral
      sites of leptin synthesis such as the gastric fundus to the brain.

PMID- 11849760
TI  - Paradoxical sleep deprivation facilitates subsequent corticosterone response to a
      mild stressor in rats.
AB  - The pituitary-adrenal responsiveness to a mild stressor was assessed in rats that
      were deprived of paradoxical sleep (PS) and in controls that were not deprived.
      Animals were either individually- or group-deprived for 96 h and hormone levels
      were assessed at 0, 5, 20 or 60 min after a saline injection+novelty and compared
      with rats which were not deprived. Both types of PS deprivation resulted in
      elevated adrenocorticotropin levels at 0 min, which peaked at 5 min in all
      animals. Individually-deprived rats exhibited the highest corticosterone (CORT)
      levels at 0 min. Peak levels were higher and occurred earlier in PS-deprived than
      in control rats (5 vs. 20 min, respectively). At 20 min, CORT levels had already
      returned to unstressed levels in PS-deprived rats, but not in control rats. These
      data indicate that PS deprivation induces facilitation of the adrenocortical
      response to a mild stressor, but do not suggest that PS deprivation changes the
      negative feedback sensitivity to CORT.

PMID- 11849761
TI  - Effects of electroacupuncture on the mechanical allodynia in the rat model of
      neuropathic pain.
AB  - The analgesic effects of acupuncture on the mechanical allodynia in the rat model
      of neuropathic pain have not yet been studied. The aim of the present study is:
      first, to determine if electroacupuncture (EA) or morphine attenuates the
      mechanical allodynia; and secondly, to examine if the EA effect may be mediated
      by endogenous opioids. To produce neuropathic pain, the right superior caudal
      trunk was resected between the S3 and S4 spinal nerves. Twenty-one days after the
      neuropathic surgery, low frequency EA stimulation (2 Hz, 0.3 ms, 0.07 mA)
      delivered to Houxi (S13) for 30 min relieved significantly the signs of
      mechanical allodynia. Intraperitoneal (i.p.) morphine (0.5 or 1.5 mg/kg) also
      relieved the signs of mechanical allodynia in a dose-dependent manner. In
      addition, the antiallodynic effect of Houxi EA was blocked by pretreatment with
      naloxone (2 mg/kg, i.p.). However, combined application of EA and morphine did
      not show an obvious synergistic effect. These results suggest that low frequency
      EA or morphine can relieve the mechanical allodynia signs and the EA effect can
      be mediated by endogenous opioid systems.

PMID- 11849762
TI  - Mechanosensitivity of spinal accessory lobe neurons in the pigeon.
AB  - In the avian lumbosacral spinal cord there are segmentally organized accessory
      lobes which protrude into the vertebral canal. These lobes consist of neurons and
      of glycogen cells. The neurons have been suggested to function as
      mechanosensitive elements in an extra-labyrinthine sense organ of equilibrium. To
      test this view, extracellular electrophysiological recordings were done during
      vibratory stimuli applied to the whole body of anesthetized pigeons. Single unit
      activity was analyzed with regard to interval distribution (interval histograms)
      and entrainment to the frequency of the stimulus (autocorrelograms). Most neurons
      were driven by a 100 or 75 Hz stimulus and there was a tight coupling to the
      phase of the stimulus. Neurons in the adjacent spinal gray substance did not
      respond to this stimulus. This strongly supports a mechanosensitive function of
      the lobe neurons.

PMID- 11849763
TI  - Reduced interhemispheric transmission in schizophrenia patients: evidence from
      event-related potentials.
AB  - Interhemispheric transfer was investigated in 14 schizophrenia patients and 15
      age- and sex-matched healthy controls in a lateralized lexical decision task.
      Words and pseudowords were tachistoscopically presented either to the left or to
      the right visual hemifield. Event-related potentials were determined from a 65
      channel electroencephalogram. Information transfer between hemispheres was
      assessed by the interhemispheric transmission time (IHTT), the N1-latency
      difference between ipsilateral and contralateral hemisphere.Controls, but not
      schizophrenia patients showed significantly faster IHTT from the right to the
      left hemisphere for words, while IHTT from the left to the right hemisphere did
      not differ between groups and stimuli. These findings are interpreted in terms of
      a deficit in schizophrenia to transfer verbal information from the right to the
      left hemisphere via the corpus callosum.

PMID- 11849764
TI  - Acetylsalicylic acid reduces heat responses in rat nociceptive primary sensory
      neurons--evidence for a new mechanism of action.
AB  - Acetylsalicylic acid (ASA) is thought to exert its peripheral analgesic effects
      via inhibition of cyclooxygenase. We now studied the effects of ASA on heat
      responses in primary nociceptive neurons by whole-cell patch-clamp and calcium
      microfluorimetry experiments. Heat-evoked inward currents in acutely dissociated
      rat dorsal root ganglion neurons were significantly reduced by ASA in a dose
      dependent and reversible manner (IC(50) 375 nM, Hill slope -2.2, maximum effect
      55%). Heat-evoked calcium transients (measured with FURA-2) were reversibly
      reduced by 53+/-14% (P<0.05) by co-application of 1 microM ASA. The low IC(50)
      value, the rapid occurrence, and the reversibility of the observed effects make
      it unlikely that inhibition of prostaglandin synthesis is involved in the
      inhibition of nociceptive heat responses by ASA, and suggest a more direct effect
      on heat transduction mechanisms.

PMID- 11849766
TI  - 14-3-3 Protein isoforms and atypical patterns of the 14-3-3 assay in the
      diagnosis of Creutzfeldt-Jakob disease.
AB  - A positive 14-3-3 assay is a criterion for probable Creutzfeldt-Jakob disease
      (CJD). Cerebrospinal fluid (CSF) 14-3-3 is usually detected by immunoblot using
      an antibody that recognizes all of the 14-3-3 isoforms. In a few cases, the
      antibody recognizes an inferior band and this pattern is associated with false
      positive results. We analyzed 43 CSF (26 CJD, 17 controls) samples using
      antibodies against specific isoforms (beta, epsilon, gamma, tau, xi) and compared
      the results with those obtained with the standard antibody. The anti-gamma and
      anti-beta antibody achieved similar results but the presence of atypical patterns
      made the standard antibody more accurate for the CJD diagnosis. To study the
      nature of the inferior band, CSF samples were probed with antibodies against
      light chain immunoglobulins, and immunoblots of human IgG with the standard
      antibody. The experiments suggested a cross-reaction of the anti-14-3-3 antibody
      with light chain immunoglobulins.

PMID- 11849765
TI  - Dipyridamole-induced increase in production of rat dopaminergic neurons from
      mesencephalic precursors.
AB  - Dipyridamole (DIP) was tested for its ability to induce dopaminergic (DA)
      phenotype in cultures from epidermal growth factor-derived mesencephalic
      precursor cells. When these cells were incubated in media containing serum, the
      DA phenotype was rarely expressed. The addition of DIP increased (about 350%) the
      number of DA cells per neurosphere. Treatment with interleukin-1 alpha also
      induced a significant increase (about 300%) in the number of tyrosine hydroxylase
      positive cells. However, the mixture of the most effective doses of these
      compounds did not induce a further increase in the number of DA cells. The
      results suggest that DIP may contribute to more efficient production of DA
      neurons for transplantation therapies in neurodegenerative diseases, and that
      this may be related to an enhancement of generation and/or survival of DA cells.

PMID- 11849767
TI  - Expression of c-Fos after noise-induced temporary threshold shift in the guinea
      pig cochlea.
AB  - c-Fos is known to be a component of a transcription factor, activator protein-1,
      which is induced by oxidative stress. Guinea pigs were exposed to 4 kHz band
      noise of 110 dB SPL for 1 or 5 h and the expression of c-Fos in the organ of
      Corti was determined using Western blotting analysis and immunocytochemistry. c
      Fos was expressed only after the noise exposure. The c-Fos expression was mainly
      found in the Hensen's cells, Claudius' cells and Deiter's cells of the basal and
      second turns of the cochlea. Since the threshold shift was temporary, the
      expression of c-Fos is therefore considered to contribute to the survival or
      protective function of the organ of Corti.

PMID- 11849768
TI  - Mutation analysis of the calpastatin gene (CAST) in patients with Alzheimer's
      disease.
AB  - The calpains, a family of calcium-dependent cysteine proteinases, and
      calpastatin, their endogenous inhibitor protein, are involved in the proteolysis
      of amyloid precursor protein, which is thought to be abnormal in patients with
      Alzheimer's disease (AD). Specific inhibitors of calpains attenuate amyloid beta
      peptide-induced neuronal death. We hypothesized that some AD patients have
      functionally deficient mutation(s) of the CAST gene encoding calpastatin, and we
      screened 40 Japanese patients with AD for mutations in the coding region of CAST.
      Nine polymorphisms, -82A/G, IVS7-96A/G, 669A/G, 1223C/G (Ser408Cys), IVS20-10C/T,
      IVS21-65G/A, IVS22+31T/C, IVS24+38Ins/DelA, and IVS25-32A/G, were identified. The
      669A allele causes skipping of exon 11, leading to the loss of 13 residues.
      Comparisons between 101 patients and 90 controls revealed no significant
      association between CAST polymorphisms and risk for AD, indicating that genomic
      variations of CAST are not likely to be substantially involved in the etiology of
      AD.

PMID- 11849769
TI  - The subthalamic nucleus has neurofibrillary tangles in argyrophilic grain disease
      and advanced Alzheimer's disease.
AB  - Neurofibrillary tangles (NFT) are present in the subthalamic nucleus (STN) of
      progressive supranuclear palsy and corticobasal degeneration, two sporadic
      tauopathies with preferential accumulation of tau with four repeats in the
      microtubule binding domain (4R tau). Since recent evidence suggests that
      argyrophilic grain disease (AGD) is also a 4R tauopathy, we hypothesized that the
      STN may also be affected in AGD. Tau immunostaining was used to evaluate NFT in
      the STN in 18 cases of AGD compared with 18 non-AGD cases matched for age, sex
      and Braak stage. AGD cases had significantly more NFT in the STN than non-AGD
      cases (P=0.008) with no relationship between NFT score and Braak stage.
      Surprisingly, NFT were also found in the STN of some non-AGD cases, notably in
      cases with advanced Braak stage (i.e. Alzheimer's disease). When AGD and non-AGD
      were considered as a whole there was a correlation between neurofibrillary
      degeneration in the STN and Braak stage. This study demonstrates that
      neurofibrillary degeneration is frequent in the STN in AGD, but also detected in
      non-AGD cases with advanced Braak stage.

PMID- 11849770
TI  - Increased nitric oxide release by transient peripheral noxious inputs to the
      spinal cord of rats: an in vivo voltammetric approach.
AB  - Using in vivo voltammetric detection of nitric oxide (NO) a previous study
      demonstrated an increased NO release at the lumbar dorsal horn level of the
      spinal cord by peripheral inflammatory processes in decerebrated-spinalized rats.
      This study concerns the effects of acute peripheral stimulations. Gentle non
      noxious or isolated nociceptive stimulation did not modify the oxidation current
      due to NO. However, transient transcutaneous repetitive electrical stimulation of
      the hindpaw at mild to high intensities (1, 3, and 6 mA) provoked increases in
      the voltammograms, which were prolonged after stimulation ceased. These effects
      were absent in animals pretreated with the N-methyl-D-aspartate channel blocker
      MK-801. The data provide novel direct evidence that NO participates, at least
      during repetitive stimulation, in the transmission of noxious afferent messages
      in the dorsal horn of the spinal cord.

PMID- 11849771
TI  - Increased serotonin release in mice frontal cortex and hippocampus induced by
      acute physiological stressors.
AB  - The effects of acute physiological stressors (5 s tail pinch, handling and forced
      swimming at +25 and +5 degrees C for 3 min each) on serotonin (5-HT) release in
      the mouse brain were investigated using in vivo microdialysis. The extracellular
      5-HT levels were determined by a newly developed highly-sensitive and selective
      high-performance liquid chromatography method based on derivatization with
      benzylamine and fluorescence detection. The basal levels of 5-HT in 3 min
      microdialysates from the ventral hippocampus and frontal cortex were 0.68+/-0.21
      and 0.75+/-0.28 fmol/6 microl (n=24), respectively. All three stressors caused an
      immediate, significant and reversible increase (handling: 150%; swimming: 240%)
      of extracellular 5-HT levels in both brain structures, suggesting a more dynamic
      role played by the serotonergic system in response to acute stress.

PMID- 11849772
TI  - Enterostatin increases extracellular serotonin and dopamine in the lateral
      hypothalamic area in rats measured by in vivo microdialysis.
AB  - The effect of enterostatin injection into the rat lateral hypothalamic area (LHA)
      on serotonin and dopamine releases in extracellular space was investigated by in
      vivo microdialysis technique. The primary focus being to understand whether a
      small amount of enterostatin crossing the blood-brain barrier correlates with
      activity changes in serotonergic and dopaminergic nervous systems or not. We
      found a significant elevation in serotonin release in the LHA. The enterostatin
      perfusion also induced a smaller but significant increase in dopamine level than
      serotonin one. This result suggests that enterostatin plays some sort of role in
      the control of feeding of fat through the control serotonergic and dopaminergic
      satiety mechanism.

PMID- 11849773
TI  - Anterograde TNF alpha transport from rat dorsal root ganglion to spinal cord and
      injured sciatic nerve.
AB  - Tumor necrosis factor-alpha (TNF alpha) is a key modulator of painful peripheral
      nerve injury. We have previously shown that a tracer of TNF alpha injected at the
      site of rat sciatic nerve injury undergoes retrograde axonal transport to the
      dorsal root ganglia (DRG). To further understand the role of TNF alpha in DRG, we
      injected rat L5 DRG with biotinylated TNF alpha, neurobiotin, or vehicle, and
      detected translocation of the biotin tag by avidin-biotin histochemistry.
      Biotinylated TNF alpha was transported intraaxonally toward the periphery of both
      normal and injured nerves. It also reached the dorsal horn of the spinal cord in
      injured rats, but not in control rats. These findings highlight a dynamic process
      of TNF alpha axonal transport in the peripheral neural axis, and help explain
      activation of central cytokines in the pathogenesis of painful neuropathy.

PMID- 11849774
TI  - Circadian motor asymmetries in humans.
AB  - Previous research studies indicate that motor activity during sleep is
      lateralized to the non-dominant hand. We put forward the hypothesis that the
      relative superiority of the non-dominant hand movements during night could arise
      from a different circadian phase relationship between the two hemispheres,
      independently of the sleep condition. The present study evaluated whether
      actigraphic data are consistent with such hypothesis. A total of 58 right-handed
      university students wore actigraphs (AMI 32K) on both left and right wrist for 3
      consecutive days. Mesor and acrophase were computed using cosinor analysis.
      Moreover, factorial analysis of variances were carried out on side (left versus
      right) and time of day. The results indicated that the left hand circadian rhythm
      had a significant phase delay in comparison to the right hand one. The mean
      activity of the left hand was significantly higher than that of the right hand
      from 20:00 until 04:00 h. The results are suggestive of a different circadian
      activation between the two hemispheres and are discussed in relation to models of
      circadian regulation of sleep/wake cycle.

PMID- 11849777
TI  - Post-radiation sensorineuronal hearing loss.

PMID- 11849775
TI  - Dinucleotide repeat polymorphisms in the neprilysin gene are not associated with
      sporadic Alzheimer's disease.
AB  - In the pathological process of Alzheimer's disease (AD), deposition of amyloid
      beta-peptide (A beta) in the brain parenchyma plays an important role. Neprilysin
      (NEP), a neutral endopeptidase, degrades A beta, and it is postulated that
      decreased NEP activity may contribute to the development of AD by promoting the
      accumulation of A beta. The human NEP gene possesses four dinucleotide repeat
      polymorphisms, and it is possible that these polymorphisms regulate the NEP
      expression levels and influence the pathological cascade of AD. Therefore, we
      investigated the association of these polymorphisms with AD. We performed
      genotyping of each polymorphism in 201 Japanese sporadic AD patients and 208
      Japanese controls. There were no significant differences between the AD and
      control groups in allele frequencies of each polymorphism. We conclude that these
      polymorphisms in the NEP gene do not contribute to genetic risk factors for
      sporadic AD.

PMID- 11849778
TI  - PAI-1 and EGFR expression in adult glioma tumors: toward a molecular prognostic
      classification.
AB  - PURPOSE: Molecular classification of gliomas is a major challenge in the effort
      to improve therapeutic decisions. The plasminogen activator system, including
      plasminogen activator inhibitor type 1 (PAI-1), plays a key role in tumor
      invasion and neoangiogenesis. Epidermal growth factor receptor (EGFR) is involved
      in the control of proliferation. The contribution of PAI-1 and EGFR to the
      survival of gliomas was retrospectively investigated. METHODS AND MATERIALS:
      Fifty-nine adult gliomas treated by neurosurgery and conventional irradiation
      were analyzed, including 9 low-grade (2) and 50 high-grade (3-4) tumors (WHO
      classification). PAI-1 was measured on cytosols and EGFR on solubilized membranes
      using ELISA methods. RESULTS: High PAI-1 levels were strongly associated with
      high histologic grade (p < 0.001) and histologic necrosis (p < 0.001). PAI-1 also
      correlated positively with patient age (p = 0.05) and negatively with Karnofsky
      index (p = 0.01). By univariate analysis of the high-grade population, higher PAI
      1 (p < 0.0001) and EGFR values (p = 0.02) were associated with shorter overall
      survival. Only PAI-1 was an independent factor in multivariate analysis. Grade 3
      tumors with low PAI-1 (100% 3-year overall survival rate) presented the same
      clinical outcome as the low-grade tumors. CONCLUSIONS: In this prognostic study,
      PAI-1 and EGFR expression revealed similarities and differences between high
      grade gliomas that were not apparent by traditional clinical criteria. These data
      strongly support that biologic factors should be included in glioma
      classification and the design of clinical trials to treat more homogeneous
      populations.

PMID- 11849779
TI  - Intensity-modulated radiation therapy for pediatric medulloblastoma: early report
      on the reduction of ototoxicity.
AB  - PURPOSE: The combination of cisplatin chemotherapy and radiation therapy for the
      treatment of medulloblastoma has been shown to cause significant ototoxicity,
      impairing a child's cognitive function and quality of life. Our purpose is to
      determine whether the new conformal technique of intensity-modulated radiation
      therapy (IMRT) can achieve lower rates of hearing loss by decreasing the
      radiation dose delivered to the cochlea and eighth cranial nerve (auditory
      apparatus). PATIENTS AND METHODS: Twenty-six pediatric patients treated for
      medulloblastoma were retrospectively divided into two groups that received either
      conventional radiotherapy (Conventional-RT Group) or IMRT (IMRT Group). One
      hundred thirteen pure-tone audiograms were evaluated retrospectively, and hearing
      function was graded on a scale of 0 to 4 according to the Pediatric Oncology
      Group's toxicity criteria. Statistical analysis comparing the rates of
      ototoxicity was performed using Fisher's exact test with two-tailed analysis.
      RESULTS: When compared to conventional radiotherapy, IMRT delivered 68% of the
      radiation dose to the auditory apparatus (mean dose: 36.7 vs. 54.2 Gy).
      Audiometric evaluation showed that mean decibel hearing thresholds of the IMRT
      Group were lower at every frequency compared to those of the Conventional-RT
      Group, despite having higher cumulative doses of cisplatin. The overall incidence
      of ototoxicity was lower in the IMRT Group. Thirteen percent of the IMRT Group
      had Grade 3 or 4 hearing loss, compared to 64% of the Conventional-RT Group (p <
      0.014). CONCLUSION: The conformal technique of IMRT delivered much lower doses of
      radiation to the auditory apparatus, while still delivering full doses to the
      desired target volume. Our findings suggest that, despite higher doses of
      cisplatin, and despite radiotherapy before cisplatin therapy, treatment with IMRT
      can achieve a lower rate of hearing loss.

PMID- 11849780
TI  - ATM mutations in female breast cancer patients predict for an increase in
      radiation-induced late effects.
AB  - PURPOSE: Mutation of the ATM gene may be associated with enhanced
      radiosensitivity and increased radiation-induced morbidity. Denaturing high
      performance liquid chromatography (DHPLC) is a powerful new technique proven to
      be sensitive and accurate in the detection of missense mutations, as well as
      small deletions and insertions. We screened female breast cancer patients for
      evidence of ATM gene alterations using DHPLC. This study attempted to determine
      whether breast cancer patients who develop severe radiotherapy (RT)-induced
      effects are more likely to possess ATM mutations than patients who display normal
      radiation responses. METHODS AND MATERIALS: Forty-six patients with early-stage
      breast carcinoma underwent limited surgery and adjuvant RT. DNA was isolated from
      blood lymphocytes, and each coding exon of the ATM gene was amplified using
      polymerase chain reaction. Genetic variants were identified using DHPLC by
      comparing test patterns with a known wild-type pattern. All variants were
      subjected to DNA sequencing and compared with wild-type sequences for evidence of
      a mutation. A retrospective review was performed, and the Radiation Therapy
      Oncology Group/European Organization for Research and Treatment of Cancer acute
      and late morbidity scoring schemes for skin and subcutaneous normal tissues were
      applied to quantify the radiation-induced effects. RESULTS: Nine ATM mutations
      were identified in 6 patients (8 novel and 1 rare). The median follow-up was 3.2
      years (range 1.3-10.3). A significant correlation between ATM mutation status and
      the development of Grade 3-4 subcutaneous late effects was found. All 3 of the
      patients (100%) who manifested Grade 3-4 subcutaneous late sequelae possessed ATM
      mutations, whereas only 3 (7%) of the 43 patients who did not develop this form
      of severe toxicity harbored an ATM mutation (p = 0.001). One ATM mutation carrier
      developed Grade 4 soft tissue necrosis after RT and required hyperbaric oxygen.
      All 3 patients manifesting Grade 3-4 late subcutaneous responses in fact harbored
      2 ATM mutations. In contrast, none of the 3 ATM carriers who had a single
      mutation developed a severe subcutaneous reaction. ATM mutation status did not
      predict for a significant increase in early effects. Of the 23 patients with
      Grade 2-3 moist desquamation, 4 (17%) had an ATM mutation compared with 2 (9%) of
      23 patients without desquamation (p = 0.7). CONCLUSION: Possession of an ATM
      mutation, particularly when 2 are present, may be predictive of an increase in
      subcutaneous late tissue effects after RT for breast cancer and may subsequently
      prove to be a relative contraindication to standard management. These patients
      may be better served with reduced doses of radiation. Equivalent local control
      remains to be tested, but this germline alteration may radiosensitize normal
      tissues, as well as the tumor itself. DHPLC is effective in the identification of
      these patients. A larger study is required to confirm these findings.

PMID- 11849781
TI  - Prediction of supraclavicular lymph node metastasis in breast carcinoma.
AB  - PURPOSE: Supraclavicular lymph node metastasis in breast cancer patients has a
      poor prognosis, and aggressive local treatment has usually resulted in severe
      morbidity. The purpose of this study was to select high-risk neck metastasis
      patients for prophylactic radiotherapy. METHODS: Between 1990 and 1998, 2658
      consecutive invasive breast cancer patients underwent surgery and adjuvant
      therapy in the hospital. The median age was 47 years (range 22-92). The median
      follow-up period was 39 months. The following factors were analyzed: age, tumor
      size, tumor location, histologic type, histologic grade, estrogen and
      progesterone receptor status, DNA flow cytometry study results, number of
      positive axillary lymph nodes, use of chemotherapy, radiotherapy, and/or hormonal
      therapy, and level of involved axillary nodes. RESULTS: Of the 2658 patients, 113
      (4.3%) developed supraclavicular lymph node metastasis during this period. Young
      age (< or =40 years), tumor size >3 cm, high histologic grade, angiolymphatic
      invasion, negative estrogen receptor status, synthetic phase fraction >4%, >4
      positive nodes, and level II or III involved nodes were all significant for
      predicting neck metastasis in the univariate analysis. Three predictive factors
      were significant after multivariate analysis: high histologic grade, >4 positive
      nodes, and axillary level II or III involved nodes. In patients with axillary
      level I involved nodes and < or =4 positive nodes, the incidence was 4.4%. If
      axillary level III was involved, the rate of supraclavicular lymph node
      metastasis was 15.1%. CONCLUSION: The incidence of supraclavicular lymph node
      metastasis was higher in the groups with >4 positive nodes and in those with
      axillary level II or III involved nodes. Selective use of comprehensive
      radiotherapy for these high-risk patients will achieve good locoregional control.

PMID- 11849782
TI  - Angiosarcoma after breast-conserving therapy: experience with hyperfractionated
      radiotherapy.
AB  - PURPOSE: To report our promising results of hyperfractionated radiotherapy (RT)
      in conjunction with surgery for angiosarcoma occurring after breast-conserving
      therapy for early-stage breast cancer. METHODS AND MATERIALS: Since 1997, 3 cases
      of angiosarcoma after breast-conserving therapy have been managed at the
      University of Florida. The histologic specimens in each case were reviewed and
      graded by one of us (J.D.R.). RESULTS: Explosive growth of discolored skin
      lesions coincident with histologic evidence of angiosarcoma characterized all 3
      cases but was preceded by a fairly indolent period (almost 2 years) of atypical
      vascular hyperplasia in 2 patients. All 3 patients were treated initially with
      radical surgery for the angiosarcoma, but extensive recurrences were noted within
      1 to 2 months of surgery. Because of the extremely rapid growth noted before and
      after surgery, hyperfractionated RT was used. Two of the patients underwent
      planned resection after RT, and neither specimen demonstrated any evidence of
      high-grade angiosarcoma. All 3 patients were alive without any recurrent disease
      22, 38, and 39 months after treatment. CONCLUSIONS: Hyperfractionated irradiation
      appears to be effective treatment for rapidly proliferating angiosarcoma. For
      previously untreated angiosarcoma, we now recommend hyperfractionated RT followed
      by surgery to enhance disease control and remove as much reirradiated tissue as
      possible.

PMID- 11849783
TI  - Clinical assessment by MRI for patients with stage II cervical carcinoma treated
      by radiation alone in multicenter analysis: are all patients with stage II
      disease suitable candidates for chemoradiotherapy?
AB  - PURPOSE: From recent randomized trials, patients with Stage II cervical carcinoma
      are thought to be candidates for chemoradiotherapy. To refine the strategy for
      Stage II patients, we performed a retrospective multi-institutional analysis
      using MRI. METHODS AND MATERIALS: From three institutions, 84 patients with Stage
      II cancer diagnosed by MRI were entered into the study. All patients received
      intracavitary brachytherapy with (n = 83) or without (n = 1) external beam
      radiotherapy. Uni- and multivariate analyses were performed to identify the
      prognostic factors for overall survival (OAS), disease-free survival (DFS),
      pelvic control (PC), and distant metastasis-free survival (DMFS). RESULTS: The 5
      year DFS rate of patients with maximal tumor size (D(max)) > or =50 mm (46.2%)
      was significantly lower than that for patients with D(max) <50 mm (88.0%; p
      <0.0001). Large size or volume and lymph node swelling were also significant
      prognostic factors of OAS, DFS, PC, and DMFS. In the multivariate model, size or
      volume was a significant prognostic factor of OAS, DFS, PC, and DMFS, and lymph
      node swelling was a prognostic factor for DFS, PC, and DMFS. Using these two
      prognostic factors, patients were divided into 3 subgroups. The 5-year DFS rate
      of patients with risk 0 (D(max) <50 mm and negative lymph node swelling), 1
      (D(max) > or =50 mm or positive lymph node swelling), and 2 (D(max) > or =50 mm
      and positive lymph nodes) was 93.2%, 53.3%, and 25.0%, respectively (p <0.0001).
      CONCLUSION: In this stage-limiting analysis, we clarified the stratification
      according to clinical risk with the aid of MRI. For patients with low-risk
      factors, especially for elderly patients, radiation alone would probability be a
      feasible option. In the future, a randomized trial using criteria with MRI would
      help to identify the optimal strategy for patients with Stage II disease.

PMID- 11849784
TI  - Phase I clinical trial of parenteral hydroxyurea in combination with pelvic and
      para-aortic external radiation and brachytherapy for patients with advanced
      squamous cell cancer of the uterine cervix.
AB  - PURPOSE: Oral hydroxyurea (HU) is a potent radiation sensitizer, but in vitro
      studies have suggested that prolonged exposure to HU by way of continuous
      parenteral infusion would enhance clinical efficacy. The objective of this study
      was to determine the maximal tolerated dose and identify the toxicities of
      continuous infusion HU in combination with pelvic and para-aortic external beam
      radiotherapy (RT) and intrauterine brachytherapy in patients with locally
      advanced carcinoma of the uterine cervix. METHODS: This Phase I study of
      concomitant RT was designed with an escalating dose schedule of HU administered
      by continuous infusion. HU was administered parenterally as a continuous
      infusion, 5 d/wk, during the first 21 days of external radiation, during the
      final 5 days of external beam RT, followed by another 5-day infusion schedule
      bracketing the single fraction of brachytherapy. The maximal tolerated dose was
      defined as the highest dose level at which 3 of 3 or 5 of 6 patients could be
      treated without dose-limiting toxicity. RESULTS: At dose level 1 (0.25
      mg/m(2)/min), 0 of 4 patients experienced Grade 4 toxicities and 2 patients
      experienced Grade 3 hematologic toxicities that were not considered dose
      limiting. One of the first 4 patients at level 2 (0.375 mg/m(2)/min) had Grade 3
      diarrhea, but the 3 subsequent patients tolerated the dose. At level 3 (0.5
      mg/m(2)/min), 4 of 5 patients failed to complete therapy without a >7-day
      interruption in HU. CONCLUSIONS: The maximal tolerated dose of parenteral HU was
      0.375 mg/m(2)/min when administered with concomitant RT. The most common
      toxicities were hematologic. A new trial, incorporating concurrent cisplatin, HU,
      and RT is planned.

PMID- 11849785
TI  - Staging and management of localized non-Hodgkin's lymphomas: variations among
      experts in radiation oncology.
AB  - PURPOSE: To examine the opinions of radiation oncology experts on the management
      of lymphomas with respect to staging procedures, treatment plan, radiation target
      volume, and dose prescription. Our aim was to identify the patterns of practice
      and areas of controversy that may need to be resolved and be amenable to
      prospective clinical trials. MATERIALS AND METHODS: Radiation oncology experts in
      lymphoma management were identified from academic centers in the United States,
      Europe, and Canada. A sample of individuals with a publication record and/or
      participation in the design and execution of lymphoma clinical trials (n = 33)
      were mailed a questionnaire of five case scenarios. The experts were asked to
      specify their approaches to staging investigations, treatment plan, radiation
      target volume, and dose prescription for each scenario. Radiation fields were
      indicated by the respondents on a schematic anatomy diagram on the questionnaire.
      The response rate to the survey was 82% (27/33). RESULTS: Staging of lymphomas
      relied on the use of imaging, because computed tomography of the abdomen and
      pelvis was recommended in all cases, and computed tomography of the uninvolved
      thorax was advocated by 70% of respondents. A lymphangiogram and a gallium scan
      were suggested by, respectively, 26% and 25% of respondents. The overall
      treatment plan was uniform for the four cases of localized presentations of
      lymphoma. However, the details of chemotherapy and radiation target volume varied
      significantly. Variations were observed in recommendations regarding the number
      of courses of chemotherapy and the extent of radiotherapy. The survey documented
      significant differences in the recommended radiation therapy (RT) dose (30-50
      Gy). The scenario of leptomeningeal relapse in diffuse large B-cell lymphoma
      documented the most diverse treatment recommendations. These varied from whole
      brain radiation alone to systemic and intrathecal chemotherapy, radiation with
      craniospinal coverage, and high-dose chemotherapy with bone marrow
      transplantation. CONCLUSIONS: This survey demonstrated a high degree of consensus
      regarding the overall management plan of localized lymphomas among the sampled
      expert radiation oncologists. However, the recommendations regarding the
      specifics of chemotherapy and RT remain variable. There is clearly no agreement
      on the most appropriate RT dose and volume. The large variation in the treatment
      of leptomeningeal relapse of diffuse large B-cell lymphoma suggests that the
      optimal treatment in this situation is poorly defined, and the clinical outcome
      with RT, as well as the rationale for decision making, should be examined in more
      detail.

PMID- 11849787
TI  - Primary radiotherapy for localized orbital MALT lymphoma.
AB  - PURPOSE: To define the natural history, prognosis, and radiocurability of
      localized orbital extranodal marginal zone lymphoma of mucosa-associated lymphoid
      tissue (MALT). METHODS AND MATERIALS: Clinical records and pathologic material of
      40 patients treated with local radiotherapy for localized orbital lymphoma were
      reviewed. Treatment consisted of 30-40 Gy in 1.8-2-Gy fractions (mean 34 Gy) of
      irradiation using 9-20-MeV electrons for conjunctival lesions, or 6-MV photons
      with complex treatment planning for retrobulbar lesions. The lens was routinely
      shielded with the use of a suspended eye bar. RESULTS: Upon pathologic review, 31
      cases of orbital MALT lymphoma were identified. With the median follow-up of 5.9
      years (range 9 months-0.3 years), the actuarial 10-year overall survival was 73%.
      Local control was 100%. Five distant failures resulted in a projected 10-year
      freedom from relapse of 71%. Most of the failures were extranodal in sites where
      MALT lymphoma has previously been shown to arise. No difference in outcome was
      observed among patients treated to less than or equal to 34 Gy vs. those treated
      to higher radiation doses. Two patients experienced clinically significant
      retinal damage after doses > or = Gy. CONCLUSION: In this study, localized
      orbital MALT lymphoma was well controlled with radiotherapy. Even following
      relapse, patients with orbital MALT lymphoma exhibited an indolent course.
      Relapse occurred predominantly in extranodal mucosal sites, implying a possible
      homing mechanism for MALT lymphoma cells. Given the excellent local control
      rates, our current treatment recommendation is to use a radiation dose of 30-30.6
      Gy in 1.5-.8-Gy fractions to minimize risk of late toxicity.

PMID- 11849788
TI  - Relationship between percent positive biopsies and biochemical outcome after
      permanent interstitial brachytherapy for clinically organ-confined carcinoma of
      the prostate gland.
AB  - PURPOSE: Recently, the percentage of positive prostate biopsies has been reported
      to be statistically significant in predicting the biochemical outcome after
      either radical prostatectomy or 3-dimensional conformal external beam
      radiotherapy. In this study, we evaluated the impact of the percentage of
      positive prostate biopsies in predicting the 5-year biochemical outcome for
      patients with clinically organ-confined prostate cancer undergoing permanent
      interstitial brachytherapy. METHODS AND MATERIALS: Two hundred sixty-two hormone
      naive patients underwent transperineal ultrasound-guided permanent prostate
      brachytherapy with generous periprostatic margins, using either 103Pd or 125I for
      clinical T1b/T2b NXM0 (1997 AJCC) adenocarcinoma of the prostate gland from April
      1995 to October 1999. No patient was lost to follow-up. The actual percentage of
      positive biopsies (number of positive biopsies/total number of biopsies) was
      determinable for 255 of the 262 patients. Of the evaluated cases, 133 patients
      were implanted with 103Pd and 122 patients with 125I. The median patient age was
      68 years (range 48-81). The median follow-up was 38.6 months (range 6-73). Follow
      up was calculated from the day of implantation. Patients were stratified by the
      percentage of positive biopsies into the following groups: <34%, 34-50%, and
      >50%. Additional clinical parameters evaluated included patient age, clinical T
      stage, Gleason score, pretreatment prostate specific antigen (PSA), risk group,
      and prostate volume. Low-risk patients were staged as clinical T1c/T2a, Gleason
      score < or =6, and pretreatment PSA < or =10 ng/mL, intermediate-risk patients
      presented with one unfavorable prognostic parameter, and high-risk patients
      presented with two or more unfavorable prognostic parameters (clinical stage T2b,
      PSA >10 ng/mL, Gleason score > or =7). Treatment parameters included the use of
      supplemental external beam radiation and choice of isotope. Biochemical disease
      free survival was defined by the American Society of Therapeutic Radiation and
      Oncology consensus definition. RESULTS: For the 255 evaluated patients, the 5
      year actuarial biochemical no evidence of disease survival rate was 92.5%. For
      patients with low, intermediate, and high-risk disease, 95.8%, 98.1%, and 79.4%
      of patients were free of biochemical failure, respectively. When each risk group
      was stratified into the percent positive biopsy categories of <34%, 34-50%, and
      >50%, no statistical difference was found in biochemical outcome for the biopsy
      subgroups. In multivariate analysis, none of the clinical or treatment parameters
      predicted for failure in the low-risk group; only Gleason score was predictive
      for intermediate-risk patients and only PSA for high-risk patients. In the
      overall population, PSA and Gleason score were both found to be predictors of
      biochemical failure, but not risk group, clinical stage, or percentage of
      positive biopsies. There was no significant dependence between the percent
      positive biopsy group and the Kaplan-Meier biochemical survival rates for any of
      the various subgroups of clinical and treatment parameters, except for clinical
      stage T1c-T2a (p = 0.006). The median postimplant PSA was 0.2 ng/mL for patients
      with either low-risk disease or <34% positive biopsies and 0.1 ng/mL for all
      other risk groups or percent positive biopsy subgroups. CONCLUSION: Although a
      significant trend was found for biochemical failure with increasing percent
      positive biopsies in the overall population, our results suggest that the
      percentage of positive biopsies is not statistically significant in predicting
      the 5-year biochemical disease-free outcome for patients with low, intermediate,
      and high-risk disease undergoing permanent prostate brachytherapy. Only the
      Gleason score in intermediate-risk patients and the pretreatment PSA level in
      high-risk patients was predictive of biochemical failure. We believe this
      relative lack of significance for the percentage of positive biopsies is a result
      of dose escalation far exceeding other radiotherapy modalities and the ability to
      aggressively treat the periprostatic region compared with radical prostatectomy
      by way of the accurate placement of periprostatic seeds.

PMID- 11849786
TI  - Outcome and patterns of failure in testicular lymphoma: a multicenter Rare Cancer
      Network study.
AB  - PURPOSE: To assess the outcome and patterns of failure in patients with
      testicular lymphoma treated by chemotherapy (CT) and/or radiation therapy (RT).
      METHODS AND MATERIALS: Data from a series of 36 adult patients with Ann Arbor
      Stage I (n = 21), II (n = 9), III (n = 3), or IV (n = 3) primary testicular
      lymphoma, consecutively treated between 1980 and 1999, were collected in a
      retrospective multicenter study by the Rare Cancer Network. Median age was 64
      years (range: 21-91 years). Full staging workup (chest X-ray, testicular
      ultrasound, abdominal ultrasound, and/or thoracoabdominal computer tomography,
      bone marrow assessment, full blood count, lactate dehydrogenase, and
      cerebrospinal fluid evaluation) was completed in 18 (50%) patients. All but one
      patient underwent orchidectomy, and spermatic cord infiltration was found in 9
      patients. Most patients (n = 29) had CT, consisting in most cases of
      cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) with (n = 17)
      or without intrathecal CT. External RT was delivered to scrotum alone (n = 12) or
      testicular, iliac, and para-aortic regions (n = 8). The median RT dose was 31 Gy
      (range: 20-44 Gy) in a median of 17 fractions (10-24), using a median of 1.8 Gy
      (range: 1.5-2.5 Gy) per fraction. The median follow-up period was 42 months
      (range: 6-138 months). RESULTS: After a median period of 11 months (range: 1-76
      months), 14 patients presented lymphoma progression, mostly in the central
      nervous system (CNS) (n = 8). Among the 17 patients who received intrathecal CT,
      4 had a CNS relapse (p = NS). No testicular, iliac, or para-aortic relapse was
      observed in patients receiving RT to these regions. The 5-year overall, lymphoma
      specific, and disease-free survival was 47%, 66%, and 43%, respectively. In
      univariate analyses, statistically significant factors favorably influencing the
      outcome were early-stage and combined modality treatment. Neither RT technique
      nor total dose influenced the outcome. Multivariate analysis revealed that the
      most favorable independent factors predicting the outcome were younger age, early
      stage disease, and combined modality treatment. CONCLUSIONS: In this multicenter
      retrospective study, CNS was found to be the principal site of relapse, and no
      extra-CNS lymphoma progression was observed in the irradiated volumes. More
      effective CNS prophylaxis, including combined modalities, should be prospectively
      explored in this uncommon site of extranodal lymphoma.

PMID- 11849789
TI  - Positive resection margin and/or pathologic T3 adenocarcinoma of prostate with
      undetectable postoperative prostate-specific antigen after radical prostatectomy:
      to irradiate or not?
AB  - PURPOSE: To evaluate the efficacy of postoperative adjuvant radiotherapy (RT) for
      positive resection margin and/or pathologic T3 (pT3) adenocarcinoma of the
      prostate with undetectable postoperative prostate-specific antigen (PSA) levels.
      METHODS AND MATERIALS: We retrospectively analyzed 125 patients with a positive
      resection margin and/or pT3 adenocarcinoma of the prostate who had undetectable
      postoperative serum PSA levels after radical prostatectomy. Seventy-three
      patients received postoperative adjuvant RT and 52 did not. Follow-up ranged from
      1.5 to 12.0 years (median 4.2 for the irradiated group and 4.9 for the
      nonirradiated group). PSA outcome was available for all patients. Freedom from
      failure was defined as the maintenance of a serum PSA level of < or =0.2 ng/mL,
      as well as the absence of clinical local recurrence and distant metastasis.
      RESULTS: No difference was found in the 5-year actuarial overall survival between
      the irradiated and nonirradiated group (94% vs. 95%). However, patients receiving
      adjuvant RT had a statistically superior 5-year actuarial relapse-free rate,
      including freedom from PSA failure, compared with those treated with surgery
      alone (88% vs. 65%, p = 0.0013). In the irradiated group, 8 patients had relapse
      with PSA failure alone. None had local or distant recurrence. In the
      nonirradiated group, 15, 1, and 2 had PSA failure, local recurrence, and distant
      metastasis, respectively. On Cox regression analysis, pre-radical prostatectomy
      PSA level and adjuvant RT were statistically significant predictive factors for
      relapse, and Gleason score, extracapsular invasion, and resection margin status
      were not. There was a suggestion that seminal vesicle invasion was associated
      with an increased risk of relapse. The morbidity of postoperative adjuvant RT was
      acceptable, with only 2 patients developing Radiation Therapy Oncology Group
      Grade 3 genitourinary complications. Adjuvant RT had a minimal adverse effect on
      urinary continence and did not cause serious gastrointestinal toxicity.
      CONCLUSION: Postoperative adjuvant RT was associated with a lower risk of
      relapse, including freedom from PSA failure, compared with observation alone for
      pT3 and/or margin-positive disease with undetectable postoperative PSA levels.
      This was accomplished with a minimal risk of serious RT morbidity.

PMID- 11849790
TI  - Sexual (dys)function after radiotherapy for prostate cancer: a review.
AB  - PURPOSE: Prostate cancer has become the most common nonskin malignant neoplasm in
      older men in Western countries. As treatment efficacy has improved, issues
      related to posttherapy quality of life and sexual functioning have become more
      important. METHODS AND MATERIALS: We discuss the various methods used to evaluate
      erectile and sexual dysfunction and the definition of potency. The etiologies of
      erectile dysfunction after external beam radiotherapy and brachytherapy for
      prostate cancer are also reviewed. The literature is summarized, and comparative
      studies of radiation and surgery are surveyed briefly. RESULTS: Rates of erectile
      dysfunction vary from 6 to 84% after external beam radiotherapy and from 0 to 51%
      after brachytherapy. In most of the studies, the analysis is retrospective, the
      definition of erectile dysfunction is not clear, only one question about sexual
      functioning is asked, and nonvalidated instruments are used. The etiology of
      erectile dysfunction after radiation for prostate cancer is not completely
      understood. CONCLUSIONS: Because erectile function is only one component of
      sexual function, it is necessary to assess sexual desire, satisfaction, frequency
      of intercourse, and other such factors when evaluating the effects of therapy.
      Patients should be offered sexual counseling and informed about the availability
      of effective treatments for erectile dysfunction, such as sildenafil,
      intracavernosal injection, and vacuum devices.

PMID- 11849791
TI  - Initial clinical experience with infrared-reflecting skin markers in the
      positioning of patients treated by conformal radiotherapy for prostate cancer.
AB  - PURPOSE: To evaluate an infrared (IR) marker-based positioning system in patients
      receiving conformal radiotherapy for prostate cancer. METHODS AND MATERIALS:
      During 553 treatments, the ability of the IR system to automatically position the
      isocenter was recorded. Setup errors were measured by means of orthogonal
      verification films and compared to conventional positioning (using skin drawings
      and lasers) in 184 treatments. RESULTS: The standard deviation of anteroposterior
      (AP) and lateral setup errors was significantly reduced with IR marker
      positioning compared to conventional: 2 vs. 4.8 mm AP (p < 0.01) and 1.6 vs. 3.5
      mm laterally (p < 0.01). Longitudinally, the difference was not significant (3.5
      vs. 3.0 mm). Systematic errors were on the average smaller AP and laterally for
      the IR method: 4.1 vs. 7.8 mm AP (p = 0.01) and 3.1 vs. 5.6 mm lateral (p =
      0.07). Longitudinally, the IR system resulted in somewhat larger systematic
      errors: 5.0 vs. 3.4 mm for conventional positioning (p = 0.03). The use of an off
      line correction protocol, based on the average deviation measured over the first
      four fractions, allowed virtual elimination of systematic errors. Inability of
      the IR system to correctly locate the markers, leading to an executional failure,
      occurred in 21% of 553 fractions. CONCLUSION: IR marker-assisted patient
      positioning significantly improves setup accuracy along the AP and lateral axes.
      Executional failures need to be reduced.

PMID- 11849792
TI  - Daily prostate targeting using implanted radiopaque markers.
AB  - PURPOSE: A system has been implemented for daily localization of the prostate
      through radiographic localization of implanted markers. This report summarizes an
      initial trial to establish the accuracy of patient setup via this system. METHODS
      AND MATERIALS: Before radiotherapy, three radiopaque markers are implanted in the
      prostate periphery. Reference positions are established from CT data. Before
      treatment, orthogonal radiographs are acquired. Projected marker positions are
      extracted semiautomatically from the radiographs and aligned to the reference
      positions. Computer-controlled couch adjustment is performed, followed by
      acquisition of a second pair of radiographs to verify prostate position. Ten
      patients (6 prone, 4 supine) participated in a trial of daily positioning.
      RESULTS: Three hundred seventy-four fractions were treated using this system.
      Treatment times were on the order of 30 minutes. Initial prostate position errors
      (sigma) ranged from 3.1 to 5.8 mm left-right, 4.0 to 10.1 mm anterior-posterior,
      and 2.6 to 9.0 mm inferior-superior in prone patients. Initial position was more
      reproducible in supine patients, with errors of 2.8 to 5.0 mm left-right, 1.9 to
      3.0 mm anterior-posterior, and 2.6 to 5.3 mm inferior-superior. After prostate
      localization and adjustment, the position errors were reduced to 1.3 to 3.5 mm
      left-right, 1.7 to 4.2 mm anterior-posterior, and 1.6 to 4.0 mm inferior-superior
      in prone patients, and 1.2 to 1.8 mm left-right, 0.9 to 1.8 mm anterior
      posterior, and 0.8 to 1.5 mm inferior-superior in supine patients. CONCLUSIONS:
      Daily targeting of the prostate has been shown to be technically feasible. The
      implemented system provides the ability to significantly reduce treatment margins
      for most patients with cancer confined to the prostate. The differences in final
      position accuracy between prone and supine patients suggest variations in
      intratreatment prostate movement related to mechanisms of patient positioning.

PMID- 11849793
TI  - Impact of biochemical failure on overall survival after radiation therapy for
      localized prostate cancer in the PSA era.
AB  - PURPOSE: To study the impact of biochemical failure on overall survival rates
      during the first 10 years after definitive radiotherapy for localized prostate
      cancer. METHODS AND MATERIALS: The analysis was performed on 936 cases treated at
      a single institution between 1986 and 1998 with definitive radiotherapy. The
      median age of treatment was 69 years (range: 46-86 years). Pretreatment PSA
      levels (iPSA) and biopsy Gleason scores (bGS) were available for all cases. The
      clinical stage was T1/T2A in 63%, T2B/C in 27%, and T3 in 10%. The median iPSA
      level was 9.6 ng/mL (range: 0.4-692.9 ng/mL). The iPSA was < or =10 in 53% and
      >10 in 47%. The bGS was < or =6 in 59% and > or =7 in 41%. Androgen deprivation
      (AD) was administered in 181 cases (19%) for a median duration of 6 months
      (range: 1-6 months). All 181 cases received AD neoadjuvantly, i.e., before and/or
      during the radiotherapy. No AD was delivered after the completion of radiation.
      The median radiation dose was 70 Gy (range: 60-78 Gy). The radiotherapy technique
      was conformal in 376 (40%) cases. The American Society of Therapeutic Radiology
      and Oncology definition of biochemical failure (bF) was used; 316 cases (34%) had
      failed biochemically, and 620 (66%) had not. The end point was overall survival
      (OS). Time to death was determined from the time of definitive radiotherapy. The
      median PSA follow-up was 58 months. The median follow-up times for bF vs. no-bF
      cases were 77 and 49 months, respectively. A multivariate analysis of factors
      affecting OS using the proportional hazards model was performed for all cases
      using the following variables: age (>65 vs. < or =65 years), race (African
      American vs. Caucasian), clinical T stage (T1-2A vs. T2B-C vs. T3), bGS (< or =6
      vs. 7 vs. > or =8), iPSA (continuous variable), use of AD (yes vs. no), year of
      therapy (continuous variable), radiation dose (continuous variable), radiation
      technique (conformal vs. standard), and biochemical failure (yes vs. no).
      RESULTS: The 5-year OS rate for the entire group was 89% (95% CI [confidence
      interval]: 86-91%). The 5-year OS rates for bF vs. no-bF patients were 89% (95%
      CI: 86-93%) and 89% (95% CI: 86-92%), respectively. The 10-year OS rate for the
      entire group was 68% (95% CI: 61-75%). The 10-year OS rates for bF vs. no-bF
      patients were 65% (95% CI: 56-74%) and 77% (95% CI: 69-84%), respectively. The
      difference between bF and no bF was not significant in predicting overall
      survival in univariate analysis (log-rank test, p = 0.68). On multivariate
      analysis, bGS (p < 0.001), T stage (p = 0.003), radiation dose (p = 0.017), year
      of therapy (p = 0.031), and age (p = 0.020) were independent predictors of death.
      iPSA levels (p = 0.33), race (p = 0.80), radiation technique (p = 0.16), and use
      of AD (p = 0.09) were not predictive of OS. Biochemical failure (p = 0.052)
      showed only a trend for independently predicting overall survival on multivariate
      analysis. CONCLUSION: Biochemical failure after definitive radiotherapy for
      localized prostate cancer is not associated with increased mortality within the
      first 10 years after initial therapy, although a trend toward worse outcome was
      observed at 10 years. Longer follow-up from initial therapy is needed to fully
      understand the impact of biochemical failure on overall survival. With longer
      follow-up, significant differences might be observed at 15 or 20 years after
      therapy.

PMID- 11849794
TI  - Risk factors for acute urinary retention requiring temporary intermittent
      catheterization after prostate brachytherapy: a prospective study.
AB  - PURPOSE: We prospectively investigated prognostic factors for men undergoing
      transperineal radioactive seed implantation for prostate cancer at the University
      of Washington. METHODS AND MATERIALS: Between February and April, 1998, 62
      consecutive unselected patients were prospectively followed after brachytherapy
      for early-stage prostate adenocarcinoma. Pretreatment variables included age,
      American Urological Association (AUA) score, uroflowimetry, and prostate volume
      by ultrasound. Nonrandomized variables included hormonal therapy, seed type, and
      use of pelvic radiotherapy. Patients were contacted by phone at one week
      postoperatively and at one-month intervals thereafter. Follow-up continued until
      all patients provided the date of last catheterization. RESULTS: Urinary
      retention rate at one week was 34% (21 of 63 patients). At one month, 29%; at
      three months, 18%; and at six months, 10%. Preoperative flow rate and post-void
      residual did not predict for retention (p =.48 and p =.58). Use of alpha
      blockers, hormonal therapy, type of seed (103Pd or 1251), or external beam
      radiotherapy had no impact on risk of retention at any followup point. Preimplant
      volume and AUA score predicted for retention on univariate analysis, but on
      multivariate analysis only postimplant volume remained significant (p =.02) for
      predicting retention risk and duration. CONCLUSION: Patients with large prostate
      size (>36 g) and higher AUA score (>10) appear to be at greater risk of risk of
      retention as well as duration of retention as defined in our study. Further
      investigation will be needed to clarify the risk of urinary retention for men
      undergoing brachytherapy.

PMID- 11849796
TI  - The role of intensity-modulated radiotherapy in the treatment of parotid tumors.
AB  - PURPOSE: To compare intensity-modulated radiotherapy (IMRT) treatment plans with
      three-dimensional conformal radiotherapy (3D-CRT) plans to investigate the
      suitability of IMRT for the treatment of tumors of the parotid gland. METHODS AND
      MATERIALS: One 3D-CRT treatment plan and 10 IMRT treatment plans with differing
      beam arrangements were produced for each of nine patient data sets. The plans
      were compared using regret analysis, dose conformity, dose to organs at risk, and
      uncomplicated tumor control probability (UTCP). RESULTS: The target dose was
      comparable in the 3D-CRT and IMRT plans, although improvements were seen when
      seven and nine IMRT fields were used. IMRT reduced the mean dose to the
      contralateral parotid gland and the maximum doses to the brain and the spinal
      cord, but increased the ipsilateral lens dose in some cases. Each IMRT
      arrangement produced a higher UTCP than the 3D-CRT plans; the largest absolute
      difference was 9.6%. CONCLUSIONS: IMRT is a suitable means for treating cancer of
      the parotid, and a five-field class solution is proposed. It produced substantial
      sparing of organs at risk and higher UTCPs than 3D-CRT and should enable dose
      escalation.

PMID- 11849795
TI  - p53 expression in human rectal tissue after radiotherapy: upregulation in normal
      mucosa versus functional loss in rectal carcinomas.
AB  - PURPOSE: In vitro, ionizing radiation of epithelial cells leads to upregulation
      of wild-type p53 and subsequent induction of p21(waf1). The effect of
      radiotherapy (RT) on the expression of these proteins in patients is unknown. We
      assessed the influence of RT on the expression of p53 and p21(waf1) in normal
      mucosa and rectal carcinomas in vivo. METHODS: Tumor and normal tissue samples
      were derived from rectal cancer patients randomized in a clinical trial in which
      the value of preoperative RT was evaluated. p53 and p21(waf1) expression was
      determined in 51 irradiated and 52 nonirradiated patients using
      immunohistochemistry. RESULTS: In normal mucosa, both p53 and p21(waf1) were
      strongly upregulated after RT compared with the expression in unirradiated normal
      tissue (p <0.001). In tumor cells, no significant difference in the expression of
      p53 or p21(waf1) was found in the irradiated vs. nonirradiated group. In the few
      rectal tumors with wild-type p53, induction of p53 after RT did not necessarily
      lead to upregulation of p21(waf1). CONCLUSION: These findings demonstrate that in
      normal mucosa, a functional p53-p21(waf1) pathway is present, whereas in tumor
      cells it is defective in almost all cases because of either p53 mutation or down-
      or upstream disruption in tumors with wild-type p53. Therefore, we believe that
      the role of p53 expression as a single prognostic marker in rectal cancer needs
      reconsideration.

PMID- 11849797
TI  - Prophylactic use of amifostine to prevent radiochemotherapy-induced mucositis and
      xerostomia in head-and-neck cancer.
AB  - PURPOSE: To determine the prophylactic properties of amifostine against acute and
      late toxicities from radiochemotherapy in patients with head-and-neck cancer.
      METHODS AND MATERIALS: Fifty patients were randomized to receive conventional
      radiotherapy (RT) (2-Gy fractions, 5 days weekly, to a total of 60-74 Gy,
      depending on the tumor localization and TNM classification) and carboplatin (90
      mg/m(2) infusion once per week before RT). Amifostine (300 mg/m(2)) was
      administered in the study group only 15-30 min before RT for 6-7.5 weeks. The
      primary study end point was the grading of acute and late nonhematologic
      toxicities (mucositis, dysphagia, xerostomia) induced by radiochemotherapy.
      Secondary end points included treatment duration, hematologic toxicity, and
      clinical outcome. RESULTS: The treatment duration was significantly shorter in
      the amifostine-treated group (p = 0.013), because treatment interruptions were
      more frequent in the control group. Acute toxicities (mucositis and dysphagia)
      were less severe in the amifostine-treated group. By Week 3, all in the control
      group experienced Grade 2 mucositis compared with only 9% in the amifostine
      treated group (p <0.0001). By Week 5, 52.2% of the patients in the control group
      experienced Grade 4 mucositis compared with 4.5% in the amifostine-treated group
      (p = 0.0006). Similar results were obtained for dysphagia. At 3 months of follow
      up, only 27% of patients in the study group experienced Grade 2 xerostomia
      compared with 73.9% in the control group (p = 0.0001). Eighteen months after
      cessation of therapy, the proportion of patients with Grade 2 xerostomia was 4.5%
      vs. 30.4% for each respective treatment group (p = 0.047). Cytoprotection with
      amifostine did not affect treatment outcome, with 90.9% complete responses in the
      amifostine-treated group compared with 78.3% in the control group (p = 0.414).
      CONCLUSION: Amifostine was effective in reducing mucositis and dysphagia
      resulting from radiochemotherapy in patients with head-and-neck cancer.
      Furthermore, amifostine reduced the severity of late xerostomia, a side effect of
      RT with long-lasting consequences. Amifostine treatment did not affect the
      clinical outcome.

PMID- 11849798
TI  - CT findings at the primary site of oropharyngeal squamous cell carcinoma within 6
      8 weeks after definitive radiotherapy as predictors of primary site control.
AB  - PURPOSE: To determine whether findings on CT studies, done 6 weeks after
      radiotherapy (RT), can predict the likelihood of ultimate control at the primary
      site in oropharyngeal carcinoma. METHODS AND MATERIALS: Forty-six patients with
      oropharyngeal squamous cell carcinoma underwent RT with curative intent. A
      minimal 2-year clinical follow-up after RT was required. The primary site CT
      findings were graded for risk of recurrence on a modified 3-point scale as
      follows: Grade 0, no detectable focal abnormalities; Grade 1, anatomic asymmetry
      or focal mass <1 cm; Grade 2, focal mass >10 mm (2a) or <50% shrinkage of the
      mass as seen on pretreatment studies (2b). RESULTS: No patients with CT findings
      of Grade 0 (n = 26) or Grade 1 (n = 5) had a primary site recurrence. One of the
      13 patients with CT findings of Grade 2a had a primary site recurrence 1 year
      after completion of RT. None of the 2 patients with CT findings of Grade 2b had a
      primary site recurrence. Ultimately, 45 of the 46 patients in this study group
      had disease control at the primary site. CONCLUSION: In the evaluation of
      oropharyngeal squamous cell carcinoma on post-RT CT studies, diffuse and
      symmetric post-RT changes of the soft tissue or asymmetry without detectable mass
      or a discrete mass < or =10 mm always indicated ultimate control at the primary
      site. Even when post-RT CT shows a discrete mass >10 mm at the primary site, the
      likelihood of local control is high (93%). The study results indicate that CT
      findings, based on this relatively small series, may not add incremental
      information beyond that of clinical examination for predicting local control but
      may be useful as a baseline if imaging surveillance is contemplated.

PMID- 11849799
TI  - Role of endocavitary brachytherapy with or without chemotherapy in cancer of the
      nasopharynx.
AB  - PURPOSE: We previously reported our preliminary experience with nasopharyngeal
      cancer boosted after 60-70 Gy external beam radiotherapy (EBRT) by fractionated
      endocavitary brachytherapy (ECBT) to cumulative doses of 78-82 Gy. As for Stage
      III-IVB disease, cisplatin (CDDP)-based neoadjuvant chemotherapy (CHT) was given.
      The aim of the present study was to define the role of ECBT more accurately.
      METHODS AND MATERIALS: Ninety-one patients with primary nasopharyngeal cancer,
      staged according to the 1997 UICC/AJCC classification system, were treated
      between 1991 and 2000 with 60-70 Gy external beam radiotherapy and 11-18 Gy ECBT.
      Of the 91 patients, 21 were treated in conjunction with CHT and 70 without CHT.
      Tumors were subdivided into undifferentiated (UD) and well, moderately, and
      poorly differentiated (WMP-D) subtypes. Treatment results were analyzed for local
      control (LC), disease-free survival (DFS), freedom from distant metastasis, and
      overall survival (OS). RESULTS: A univariate and multivariate Cox regression
      analysis found stage, treatment period, age, and grade significant for LC, DFS,
      and OS. At 2 years, for Stage I-IIB (1st period, 1991-1996), the LC, DFS, and OS
      were 96%, 88%, and 80%, respectively, vs. 65%, 46%, and 52% for Stage III-IVB.
      For the 2nd treatment period (1996-2000; CHT for Stage III-IVB), the LC, DFS, and
      OS at 2 years was 100%, 90%, and 61% (Stage I-IIB), respectively, vs. 86%, 74%,
      and 66% (Stage III-IVB). Three prognostic groups (PGs) were constructed. For the
      1991-1996 period, at 2 years, patients in the good PG (UD Stage I-IIB disease)
      had 100% LC and 92% OS; those in the intermediate PG (UD Stage III-IVB or WMP-D
      Stage I-IIB), had 94% LC and 71% OS; and those in the poor PG (WMP-D Stage III
      IVB) had 47% LC and 40% OS. For the 1996-2000 period, at 2 years, the good PG had
      100% LC and 88% OS; the intermediate PG had 100% LC and 64% OS; and the poor PG
      had 71% LC and 60% OS. CONCLUSION: For Stage I-IIB disease treated between 1991
      and 2000, at 3 years, the LC and OS was 97% and 67%, respectively. The results
      with 77-81 Gy without CHT warrant EBRT combined with ECBT to remain our standard
      of care for Stage I-IIB disease. For N2-3 and/or T3-4 tumors, in addition to high
      doses of RT, neoadjuvant CHT was administered as of 1996. For the 1991-2000
      period, at 3 years, the LC was 86% and the OS was 72% with CHT, with little extra
      morbidity; they were 68% and 35% without CHT. Because of better target coverage
      and sparing, T3-4 tumors are currently boosted by stereotactic RT to 81.2 Gy.

PMID- 11849800
TI  - ARCON: experience in 215 patients with advanced head-and-neck cancer.
AB  - PURPOSE: "ARCON" combines accelerated radiotherapy to counteract tumor
      repopulation with carbogen breathing and nicotinamide to reduce chronic and acute
      hypoxia. The aim of this Phase II study was to assess the feasibility, toxicity,
      and potential effectiveness of ARCON for advanced head-and-neck cancer. METHODS
      AND MATERIALS: The study included 215 patients with head-and-neck carcinoma
      distributed as follows: larynx, n = 100; hypopharynx, n = 50; oropharynx, n = 52;
      oral cavity, n = 13; Stage II, n = 8, Stage III, n = 71, and Stage IV, n = 136.
      Accelerated radiotherapy was given to a total dose of 64-68 Gy in 2-Gy fractions
      within 36-38 days. This was combined with carbogen breathing during irradiation
      and administration of nicotinamide (60-80 mg/kg) 1-1.5 h before irradiation.
      RESULTS: There was full compliance with carbogen breathing in 88% of the
      patients. A nicotinamide dose of 80 mg/kg produced severe nausea and vomiting,
      necessitating discontinuation of the drug, in 31% of the patients. Adjustment of
      the dose to 60 mg/kg and antiemesis prophylaxis reduced the discontinuation rate
      to 10%. Confluent mucositis was observed in 91% of the patients with a median
      duration of 6 weeks. Grade 4 late complications occurred in 5% of the patients.
      The actuarial 3-year local control rates were 80% for larynx, 69% for
      hypopharynx, 88% for oropharynx, and 37% for oral cavity tumors. For T3-4 tumors,
      the local control rates were 80% for larynx, 60% for hypopharynx, 87% for
      oropharynx, and 29% for oral cavity. Regional control rates were 100% for N0, 93%
      for N1, and 74% for N2 disease. CONCLUSION: ARCON yields high local and regional
      control rates in advanced head-and-neck carcinomas, and compliance is
      satisfactory and morbidity acceptable. The local control rate of 80% for T3 and
      T4 larynx carcinomas offers excellent possibilities for organ preservation.

PMID- 11849801
TI  - Only sociodemographic variables predict quality of life after radiography in
      patients with head-and-neck cancer.
AB  - PURPOSE: Psychosocial factors influence patient compliance and have an effect on
      survival. Identifying patients at risk of decreased quality of life (QOL) with no
      extra expenditure in terms of hospital staff time or resources is mandatory to
      plan psychosocial support. METHODS AND MATERIALS: Between 1997 and 2000, 242
      patients with head-and-neck cancer (30% pharyngeal, 29% oropharyngeal, and 13%
      laryngeal cancer) were screened. Of these, 28.5% refused to participate and 19.0%
      were excluded (Karnofsky performance score <50, language and cognitive deficits,
      death, or noncompliance). A total of 124 patients were assessed with the
      Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire at ti1
      (beginning of radiotherapy [RT]). Eighty-three patients from this group were
      examined, with complete data from ti1 to ti3 (6 weeks after RT). RESULTS: The QOL
      did not change during RT. In logistic regression analysis, medical information,
      in contrast to sociodemographic variables, turned out to have no influence on the
      ability to predict low QOL (sensitivity 80% vs. 32%). Four sociodemographic
      variables were entered in the regression model (children, currently employment,
      ethanol abuse, level of secondary education) and accounted for 26% of variance in
      QOL at ti3. CONCLUSION: By routinely obtaining clinical information from the
      patient's history, patients at risk of low QOL after RT can be identified and
      could benefit from early psychosocial support.

PMID- 11849802
TI  - Papillary thyroid carcinoma: prognostic factors and the role of radioiodine and
      external radiotherapy.
AB  - PURPOSE: To evaluate the role of radioiodine and external radiotherapy treatment
      in papillary thyroid carcinoma (PTC). METHODS AND MATERIALS: This is a
      retrospective study of 842 patients with the diagnosis of PTC registered from
      1960 to 1997 at the Department of Clinical Oncology, Queen Elizabeth Hospital,
      Hong Kong. The mean follow-up was 9.2 years. The stage distribution according to
      UICC/AJCC TNM staging was as follows: 58.6%, Stage I; 9.6%, Stage II; 26.1%,
      Stage III; 2.3%, Stage IV; and 3.4%, not stated. RESULTS: The 10-year cause
      specific survival (CSS) rates were as follows: Stage I, 99.8%; Stage II, 91.8%;
      Stage III, 77.4%; and Stage IV, 37.1%. Multivariate analysis showed that the
      statistically significant poor prognostic factors for CSS were as follows: age
      older than 45, postoperative gross locoregional (LR) residual disease, distant
      metastasis (DM) at presentation, and lack of radioactive iodine (RAI) treatment.
      In patients with no DM and no postoperative LR disease, adjuvant RAI ablation
      reduced both LR failure (RR [relative risk] = 0.29) and DM (RR = 0.2), although
      the CSS was not affected. In the subgroup of T1N0 M0 disease, no patient with RAI
      treatment had a relapse. External radiotherapy reduced the risk of LR failure to
      0.35. Subgroup analysis revealed that external radiotherapy was particularly
      effective in increasing the probability of LR control of disease in patients with
      gross postoperative LR disease (RR = 0.36). CONCLUSIONS: Both RAI and external
      radiotherapy were effective treatment in PTC. Total or near-total thyroidectomy
      followed by RAI treatment appears to result in the best outcome. External
      radiotherapy to improve LR control is indicated in patients with gross
      postoperative residual disease. Treatment should be individualized for patients
      with T1N0 M0 disease.

PMID- 11849803
TI  - Combined adjuvant radiation and interferon-alpha 2B therapy in high-risk melanoma
      patients: the potential for increased radiation toxicity.
AB  - PURPOSE: Surgically resected melanoma patients with high-risk features commonly
      receive adjuvant therapy with interferon-alpha 2b combined with radiation
      therapy; the purpose of our study was to evaluate the potential enhancement of
      radiation toxicity by interferon. METHODS AND MATERIALS: Patients at LDS Hospital
      and the University of Utah Medical Center in Salt Lake City treated with
      interferon during radiotherapy or within 1 month of its completion were
      retrospectively identified, and their charts were reviewed. If possible, the
      patients were asked to return to the LDS Hospital radiation therapy department
      for follow-up. RESULTS: Five of 10 patients receiving interferon-alpha 2b therapy
      during radiation therapy or within 1 month of its completion experienced severe
      subacute/late complications of therapy. Severe subacute/late complications
      included two patients with peripheral neuropathy, one patient with radiation
      necrosis in the brain, and two patients with radiation necrosis in the s.c.
      tissue. One patient with peripheral neuropathy and one patient with radiation
      necrosis also developed lymphedema. CONCLUSIONS: In vitro studies have identified
      a radiosensitizing effect by interferon-alpha on certain cell lines, which
      suggests the possibility that patients treated with interferon and radiation
      therapy may experience more severe radiation toxicities. We have observed severe
      subacute/late complications in five of 10 patients treated with interferon-alpha
      2b during radiation therapy or within 1 month of its completion. Although an
      observational study of 10 patients lacks the statistic power to reach conclusions
      regarding the safety and complication rates of combined interferon and radiation
      therapy, it is sufficient to raise concerns and suggest the need for prospective
      studies.

PMID- 11849804
TI  - Postoperative radiotherapy in thymic carcinoma: treatment results and prognostic
      factors.
AB  - PURPOSE: To analyze the treatment results and prognostic factors of patients with
      primary thymic carcinoma treated by total or subtotal tumor resection followed by
      radiotherapy alone. METHODS AND MATERIALS: Between October 1987 and October 1997,
      26 patients with thymic carcinoma were treated with complete or incomplete
      surgical resection and postoperative adjuvant irradiation without chemotherapy.
      The radiation was delivered with 10-MV X-ray given 5 days per week at 1.8 to 2 Gy
      per fraction. Total doses ranged from 40 to 70 Gy. All patients had at least 40
      months of follow-up. RESULTS: The 5-year overall survival rate, local control
      rate, and distant metastasis-free rate were 77%, 91%, and 57%, respectively.
      Several prognostic factors, including sex, age, extent of resection (total
      resection vs. subtotal resection), Masaoka staging (early Stage I + II vs.
      advanced Stage III + IV), pathology (low-grade vs. high-grade), and postoperative
      radiation dose (> or =60 Gy vs. <60 Gy), were evaluated in univariate analysis.
      The Masaoka staging system was the only statistically significant predictor in
      overall survival rate (p = 0.0482) and distant metastasis-free rate (p = 0.0193).
      CONCLUSIONS: The Masaoka staging system is the most important prognostic factor
      in primary thymic carcinoma patients receiving postoperative radiotherapy alone.
      For resectable tumors, surgery and postoperative radiotherapy can achieve good
      local control, but the distant metastatic rate is still high. Further
      investigation of more effective chemotherapy is needed.

PMID- 11849805
TI  - Treatment of recurrent gynecologic malignancies with iodine-125 permanent
      interstitial irradiation.
AB  - PURPOSE: To analyze the outcome of permanent 125I interstitial radiotherapy for
      unresectable retroperitoneal recurrences of gynecologic malignancies. METHODS AND
      MATERIALS: A retrospective review of 20 patients treated between 1979 and 1993
      was performed to evaluate survival and morbidity associated with the interstitial
      125I technique. RESULTS: Nineteen tumors were located on the lateral pelvic wall
      and one in the para-aortic region. Eight patients, not previously irradiated,
      received external beam radiotherapy (EBRT) along with 125I interstitial implants
      placed at the time of celiotomy. Nineteen (95%) are dead of disease at 1-69
      months of follow-up. The median survival was 7.7 months for patients treated with
      125I alone and 25.4 months for those treated with both 125I and EBRT. One patient
      is alive without evidence of disease 69 months after 125I implantation. Fistulas,
      bowel obstructions, and fatal complications occurred only among patients
      previously irradiated. CONCLUSIONS: When used in a previously irradiated field,
      125I interstitial radiotherapy has major morbidity and is unlikely to be
      associated with cure or long-term survival. In radiotherapy-naive patients with
      unresectable isolated recurrent gynecologic malignancies, 125I implants and EBRT
      are feasible and occasionally may contribute to long-term disease-free survival.

PMID- 11849806
TI  - Burnout in radiation therapists: the predictive value of selected stressors.
AB  - PURPOSE: As cancer caregivers, radiation therapists experience a variety of
      stresses that may develop into burnout, which has been demonstrated to impact
      patient care, employee health, and organizational effectiveness. The purpose of
      the study was to assess the levels of radiation therapists' burnout at three
      stages. Additionally, the ability of selected workplace variables to predict each
      of the three stages of burnout was examined. METHODS AND MATERIALS: We used
      descriptive and inferential statistical analyses on reliable and valid
      instruments, which measured stress, burnout, and social support. RESULTS:
      Radiation therapists have high levels of the first two stages of burnout:
      emotional exhaustion and depersonalization. Although personal stress,
      organizational stress, guidance, reassurance of worth, and work load predicted
      50% or more of the variance in emotional exhaustion and depersonalization, their
      predictive ability for personal accomplishment was low. CONCLUSION: Efforts to
      alleviate burnout among radiation therapists within an organization should have
      positive effects, including increased quality of patient care, improved quality
      of work life, higher levels of job satisfaction, and commitment and lower staff
      turnover.

PMID- 11849807
TI  - Study of the G2/M cell cycle checkpoint in irradiated mammary epithelial cells
      overexpressing Cul-4A gene.
AB  - PURPOSE: Members of the cullin gene family are known to be involved in cell cycle
      control. One of the cullin genes, Cul-4A, is amplified and overexpressed in
      breast cancer cells. This study investigates the effect of Cul-4A overexpression
      upon G2/M cell cycle checkpoint after DNA damage induced by either ionizing or
      nonionizing radiation. METHODS AND MATERIALS: The normal mammary epithelial cell
      line MCF10A was stably transfected with full-length Cul-4A cDNA. Independent
      clones of MCF10A cells that overexpress Cul-4A proteins were selected and treated
      with either 8 Gy of ionizing radiation or 7 J/M(2) of UV radiation. The profile
      of cell cycle progression and the accumulation of several cell cycle proteins
      were analyzed. RESULTS: We found that overexpression of Cul-4A in MCF10A cells
      abrogated the G2/M cell cycle checkpoint in response to DNA damage induced by
      ionizing irradiation, but not to DNA damage induced by nonionizing radiation.
      Analysis of cell cycle proteins showed that after ionizing irradiation, p53
      accumulated in the mock-transfected MCF10A cells, but not in the Cul-4A
      transfectants. CONCLUSION: Our results suggest a role for Cul-4A in tumorigenesis
      and/or tumor progression, possibly through disruption of cell cycle control.

PMID- 11849808
TI  - Radiosensitization of human glioma cells in vitro and in vivo with acyclovir and
      mutant HSV-TK75 expressed from adenovirus.
AB  - PURPOSE: We recently reported that an adenovirus-expressing mutant HSV-TK75
      (AdCMV-TK75) radiosensitized rat syngeneic gliomas in combination with low
      concentrations of acyclovir (ACV) much more effectively than a virus expressing
      wild-type herpes simplex virus thymidine kinase (HSV-TK). In this report we have
      examined whether similar radiosensitizing effects are also seen with human glioma
      cells in vitro and in vivo. METHODS AND MATERIALS: Human U87 MG glioma cells were
      transduced with AdCMV-TK75 and exposed to ACV followed by single-dose irradiation
      and colony-forming survival assays. Similarly, U87 MG xenografts were infused
      with AdCMV-TK75 or Adbetagal control virus, followed by ACV administration and
      fractionated irradiation. Therapeutic efficacy was monitored by tumor growth.
      RESULTS: U87 MG cells transduced with AdCMV-TK75 were significantly more
      sensitive to ACV (3 microM) than cells transduced with either wild-type HSV-TK or
      control virus. To determine whether human cells also demonstrate improved
      radiosensitization similar to that seen with rat glioma cells and tumors, we
      transduced U87 MG cells with either AdCMV-TK75, AdCMV-TK, expressing wild-type
      HSV-TK, or Adbetagal and then treated the cells with 3 microM of ACV. Cells
      transduced with AdCMV-TK75 were significantly more radiosensitive (dose
      enhancement ratio [D(37)]: 2.6) by colony-forming survival assay than cells
      transduced with either AdCMV-TK or Adbetagal. Furthermore, we found that U87 MG
      xenografts infused with AdCMV-TK75 by slow positive pressure infusion were more
      radiosensitive after administration of ACV than tumors infused with Adbetagal. A
      more dramatic result was achieved when fractionated irradiation was carried out
      concurrently with ACV administration, in which case AdCMV-TK75-treated tumors did
      not grow at all. CONCLUSIONS: These results demonstrate that transduction of
      human glioma cells in vitro and infusion of xenografts in vivo with AdCMV-TK75
      and treatment with concentrations of ACV that can be achieved in vivo produce
      similar radiosensitization, as previously reported with rat glioma cells and
      intracerebral syngeneic tumors. In addition, concurrent treatment with ACV and
      radiation therapy is more efficient than when ACV is administered before
      radiation therapy.

PMID- 11849809
TI  - Multiparameter fluorescence mapping of nonprotein sulfhydryl status in relation
      to blood vessels and hypoxia in cervical carcinoma xenografts.
AB  - PURPOSE: Aberrant architecture of the tumor vasculature and temporal fluctuations
      in blood flow can result in tumor hypoxia. The aim of this study was to classify
      tumor hypoxia based on distance to blood vessels, and to characterize its
      biologic significance by determining levels of nonprotein sulfhydryls (NPSH) in
      hypoxic regions located proximally and distally to tumor blood vessels. METHODS
      AND MATERIALS: A dual fluorescence method was developed for the spatial
      colocalization of the vasculature and hypoxia in frozen sections from SiHa
      cervical carcinoma xenografts. A parallel section was stained with the sulfhydryl
      stain mercury orange. Composite fluorescence images were generated by imaging and
      tiling individual fields of view into 2D image arrays. Image arithmetic
      techniques were combined with feature-based image segmentation to characterize
      expression of NPSH as a function of the hypoxic tumor microenvironment. RESULTS:
      NPSH levels were higher in hypoxic areas of the SiHa xenografts (15.1 +/- 0.5 vs.
      13.5 +/- 0.5 integrated optical density [IOD], p < 0.03). When tumor hypoxia was
      classified by distance to the nearest visible blood vessel, significantly higher
      NPSH levels were found in hypoxic regions close to blood vessels than in regions
      at a distance from blood vessels. CONCLUSION: The results of this study indicate
      differential expression of NPSH levels in regions of hypoxia that are proximal or
      distal to blood vessels in SiHa tumors.

PMID- 11849810
TI  - The optimal fraction size in high-dose-rate brachytherapy: dependency on tissue
      repair kinetics and low-dose rate.
AB  - BACKGROUND AND PURPOSE: Indications of the existence of long repair half-times on
      the order of 2-4 h for late-responding human normal tissues have been obtained
      from continuous hyperfractionated accelerated radiotherapy (CHART). Recently,
      these data were used to explain, on the basis of the biologically effective dose
      (BED), the potential superiority of fractionated high-dose rate (HDR) with large
      fraction sizes of 5-7 Gy over continuous low-dose rate (LDR) irradiation at 0.5
      Gy/h in cervical carcinoma. We investigated the optimal fraction size in HDR
      brachytherapy and its dependency on treatment choices (overall treatment time,
      number of HDR fractions, and time interval between fractions) and treatment
      conditions (reference low-dose rate, tissue repair characteristics). METHODS AND
      MATERIALS: Radiobiologic model calculations were performed using the linear
      quadratic model for incomplete mono-exponential repair. An irradiation dose of 20
      Gy was assumed to be applied either with HDR in 2-12 fractions or continuously
      with LDR for a range of dose rates. HDR and LDR treatment regimens were compared
      on the basis of the BED and BED ratio of normal tissue and tumor, assuming repair
      half-times between 1 h and 4 h. RESULTS: With the assumption that the repair half
      time of normal tissue was three times longer than that of the tumor,
      hypofractionation in HDR relative to LDR could result in relative normal tissue
      sparing if the optimum fraction size is selected. By dose reduction while keeping
      the tumor BED constant, absolute normal tissue sparing might therefore be
      achieved. This optimum HDR fraction size was found to be largely dependent on the
      LDR dose rate. On the basis of the BED(NT/TUM) ratio of HDR over LDR, 3 x 6.7 Gy
      would be the optimal HDR fractionation scheme for replacement of an LDR scheme of
      20 Gy in 10-30 h (dose rate 2-0.67 Gy/h), while at a lower dose rate of 0.5 Gy/h,
      four fractions of 5 Gy would be preferential, still assuming large differences
      between tumor and normal tissue repair half-times and equal overall treatment
      time. For the same fraction size, an even larger normal tissue sparing can be
      obtained by prolongation of the HDR overall treatment time. CONCLUSION:
      Radiobiologic model calculations presented here aim to demonstrate that
      hypofractionation in HDR might have its opportunities for widening the
      therapeutic window, but definitely has its limits. For each specific combination
      of the parameters, a theoretical optimal HDR fraction size with regard to
      relative or absolute normal tissue sparing can be estimated, but because of
      uncertainty in the biologic parameters, these hypofractionation schemes cannot be
      generalized for all HDR brachytherapy indications.

PMID- 11849811
TI  - The effect of high-dose-rate brachytherapy dwell sequence on cell survival.
AB  - PURPOSE: During a high-dose-rate (HDR) brachytherapy treatment, as the source
      steps through different dwell positions, the dose rate at any fixed point within
      the implant varies, because the distance between the point and the source
      continually changes. The instantaneous dose rate may vary by a factor of 100 or
      more, in a complex dwell position sequence. Two different points which receive
      the same total dose may have received that dose with a very different sequence of
      dose rates. Any effects due to the complex changes in dose rate, including the
      sequence of dose delivery, are ignored. We investigated the possible effects of
      the sequence in which dose is delivered at two different dose rates,
      representative of dose rates that occur during an HDR treatment. METHODS AND
      MATERIALS: The target consisted of a tube containing a 1.0 cm(3) suspension of V
      79 Chinese hamster cells. Two fixed source dwell positions near and far from the
      target, representing high and intermediate dose rates, were considered. The
      experiments compared the survival of V-79 cells exposed to an irradiation
      sequence consisting of either an HDR component followed by an intermediate-dose
      rate component (H-I arm), or the reverse (I-H arm). In either case, the total
      dose and the dose ratio were the same, only the order in which the high- or
      intermediate-dose-rate components of the dose were delivered was changed.
      RESULTS: When the intermediate-dose-rate component was given before the HDR
      component, there was increased survival. All data pairs from three experiments
      showed greater survival for the I-H arm than the H-I arm by amounts ranging from
      4% to 24%. Simple linear-quadratic models such as the Lea-Catchside model, which
      is invariant to time reversal of irradiation sequence, do not predict these
      results. CONCLUSIONS: These results suggest that targets receiving the same total
      dose of radiation during an HDR implant may not experience the same biological
      effect. This may be related to induced radioresistance or sublethal damage
      repair.

PMID- 11849813
TI  - Risk analysis of Leksell Gamma Knife Model C with automatic positioning system.
AB  - PURPOSE: This study was conducted to evaluate the decrease in risk from
      misadministration of the new Leksell Gamma Knife Model C with Automatic
      Positioning System compared with previous models. METHODS AND MATERIALS: Elekta
      Instruments, A.B. of Stockholm has introduced a new computer-controlled Leksell
      Gamma Knife Model C which uses motor-driven trunnions to reposition the patient
      between isocenters (shots) without human intervention. Previous models required
      the operators to manually set coordinates from a printed list, permitting
      opportunities for coordinate transposition, incorrect helmet size, incorrect
      treatment times, missing shots, or repeated shots. RESULTS: A risk analysis was
      conducted between craniotomy involving hospital admission and outpatient Gamma
      Knife radiosurgery. A report of the Institute of Medicine of the National
      Academies dated November 29, 1999 estimated that medical errors kill between
      44,000 and 98,000 people each year in the United States. Another report from the
      National Nosocomial Infections Surveillance System estimates that 2.1 million
      nosocomial infections occur annually in the United States in acute care hospitals
      alone, with 31 million total admissions. CONCLUSIONS: All medical procedures have
      attendant risks of morbidity and possibly mortality. Each patient should be
      counseled as to the risk of adverse effects as well as the likelihood of good
      results for alternative treatment strategies. This paper seeks to fill a gap in
      the existing medical literature, which has a paucity of data involving risk
      estimates for stereotactic radiosurgery.

PMID- 11849812
TI  - Neutron capture therapy of intracerebral melanoma: enhanced survival and cure
      after blood-brain barrier opening to improve delivery of boronophenylalanine.
AB  - PURPOSE: Multicentric cerebral metastases of melanoma represent an important
      clinical problem for which there currently is no satisfactory treatment. We
      previously developed a model for melanoma metastatic to the brain employing nude
      rats bearing intracerebral implants of the human MRA27 melanoma. The purpose of
      the present study was to determine if the efficacy of boron neutron capture
      therapy (BNCT) could be improved by either Cereport (RMP-7) mediated modulation
      of blood-brain barrier (BBB) permeability or hyperosmotic mannitol-induced BBB
      disruption using boronophenylalanine (BPA) as the capture agent. METHODS AND
      MATERIALS: Biodistribution studies were carried out at 0.5, 2.5, and 4 h after
      intracarotid administration of Cereport (1.5 microg/kg) and intracarotid or i.v.
      administration of BPA (500 mg/kg). Peak tumor boron concentrations (65.4
      microg/g) and the best composite tumor:brain (6.1:1) and tumor:blood (6.3:1)
      ratios were observed at 2.5 h after intracarotid administration. BNCT was
      initiated at the Brookhaven Medical Research Reactor 13-14 days after
      intracerebral implantation of 10(6) MRA27 cells. RESULTS: Untreated control rats
      had a median survival time (MeST) of 22 days and for irradiated controls, it was
      30 days. Rats that received i.v. or intracarotid BPA without Cereport followed by
      BNCT 2.5 h later had MeSTs of 41 days and 57 days, respectively, with 20% long
      term survivors (>180 days) in the latter group. Rats that received intracarotid
      BPA with Cereport had an MeST of 86 days with 36% long-term survivors, which was
      very close to that of rats that had hyperosmotic mannitol-induced disruption of
      the BBB (85 days with 25% long-term survivors). When these two groups were
      combined, and survival times were compared, using the Wilcoxon rank sum test, to
      those of rats that received intracarotid BPA without blood-brain barrier
      disruption, these differences were significant at the level p = 0.01.
      CONCLUSIONS: Our data show that optimizing the delivery of BPA by means of
      intracarotid injection combined with opening the BBB by infusing Cereport or a
      hyperosmotic solution of mannitol significantly enhanced survival times and
      produced long-term cures of MRA27 melanoma-bearing rats. These observations are
      relevant to future clinical studies using BNCT for the treatment of intracerebral
      melanoma.

PMID- 11849814
TI  - In regard to "of scientific physicians and evidence-based medicine," IJROBP
      2001;49:619-621.

PMID- 11849815
TI  - In regard to Rosenzweiz et al. IJROBP 2001;50:681-685.

PMID- 11849817
TI  - How did we survive before NSMAs?

PMID- 11849819
TI  - The role of nicotinic acetylcholine receptors in the mechanisms of anesthesia.
AB  - Nicotinic acetylcholine receptors are members of the ligand-gated ion channel
      superfamily, that includes also gamma-amino-butiric-acid(A), glycine, and 5
      hydroxytryptamine(3) receptors. Functional nicotinic acetylcholine receptors
      result from the association of five subunits each contributing to the pore
      lining. The major neuronal nicotinic acetylcholine receptors are heterologous
      pentamers of alpha4beta2 subunits (brain), or alpha3beta4 subunits (autonomic
      ganglia). Another class of neuronal receptors that are found both in the central
      and peripheral nervous system is the homomeric alpha7 receptor. The muscle
      receptor subtypes comprise of alphabetadeltagamma (embryonal) or
      alphabetadeltaepsilon (adult) subunits. Although nicotinic acetylcholine
      receptors are not directly involved in the hypnotic component of anesthesia, it
      is possible that modulation of central nicotinic transmission by volatile agents
      contributes to analgesia. The main effect of anesthetic agents on nicotinic
      acetylcholine receptors is inhibitory. Volatile anesthetics and ketamine are the
      most potent inhibitors both at alpha4beta2 and alpha3beta4 receptors with
      clinically relevant IC(50) values. Neuronal nicotinic acetylcholine receptors are
      more sensitive to anesthetics than their muscle counterparts, with the exception
      of the alpha7 receptor. Several intravenous anesthetics such as barbiturates,
      etomidate, and propofol exert also an inhibitory effect on the nicotinic
      acetylcholine receptors, but only at concentrations higher than those necessary
      for anesthesia. Usual clinical concentrations of curare cause competitive
      inhibition of muscle nicotinic acetylcholine receptors while higher
      concentrations may induce open channel blockade. Neuronal nAChRs like alpha4beta2
      and alpha3beta4 are inhibited by atracurium, a curare derivative, but at low
      concentrations the alpha4beta2 receptor is activated. Inhibition of sympathetic
      transmission by clinically relevant concentrations of some anesthetic agents is
      probably one of the factors involved in arterial hypotension during anesthesia.

PMID- 11849820
TI  - Sexual dimorphism in the pituitary-adrenal response to tumor necrosis factor
      alpha, but not to interleukin-6, in the rat.
AB  - It is known that the pituitary-adrenal responses to lipopolysaccharide and
      interleukin (IL)-1 are sexually dimorphic in rodents, with females having an
      enhanced secretion of adrenocorticotropin (ACTH) and corticosterone. This study
      investigated whether the ACTH and corticosterone responses to tumor necrosis
      factor (TNF)-alpha and IL-6, two principal proinflammatory cytokines, are also
      modulated by the sex steroid milieu in the rat. Mature male and female rats
      received an intravenous administration of TNF-alpha(10 microg/kg) and IL-6 (10
      microg/kg), and changes in plasma ACTH and corticosterone levels were determined
      over time. The effect of gonadectomy on the hormonal responses was also examined
      in both sexes. TNF-alpha induced significantly higher responses of ACTH and
      corticosterone in females than in males, and this sexual difference was abolished
      by gonadectomy in both sexes. By contrast, the hormonal responses to IL-6 were
      not significantly affected by either gender or gonadectomy. These results suggest
      a sex steroid-dependent modulation of the TNF-alpha-induced, but not the IL-6
      induced, ACTH and corticosterone secretion in the rat. Further evidence for the
      sexually dimorphic neuroimmunoendocrine activity is reported herein.

PMID- 11849821
TI  - Environment associated with morphine and experience of aggression modulate
      behaviors of postdependent mice.
AB  - Contexts associated with drug use can acquire secondary reinforcing properties.
      Furthermore, context-specific withdrawal has been observed to reflect a
      relatively long-lasting learned response. The aim of this study was to evaluate
      the effect of the environment paired with morphine after 15 days of abstinence.
      In the first experiment, isolated male mice received saline or morphine either in
      their home cage or in the distinctive environment, performing two agonistic
      encounters in the distinctive environment during spontaneous withdrawal. Similar
      groups were assigned but without aggression encounters during withdrawal. In the
      second experiment, animals received saline or morphine as previously described
      but suffered two naloxone-induced withdrawals during agonistic encounters. In all
      cases, after the second withdrawal, animals were drug-free during 15 days and
      then an aggression test took place in the distinctive environment. Results show
      that experience of aggression during this spontaneous withdrawal causes an
      increase in the level of aggression exhibited when animals are drug free, in
      comparison with others in which this experience does not exist. Environment
      associated with morphine administration decreases conditioned physical signs of
      withdrawal and to a smaller extent aggression. It could be suggested that
      environment associated with morphine administration decreases the abnormal
      behaviors exhibited in postdependent mice.

PMID- 11849822
TI  - Effects of intracerebroventricular administration of 7-nitroindazole on tolerance
      to ethanol.
AB  - Previous studies have shown that nitric oxide (NO) is involved in the development
      of rapid tolerance to the motor incoordination produced by ethanol. In order to
      further investigate this involvement, three experiments were undertaken using the
      tilt-plane and the hypothermia tests. The first demonstrated that 7-nitroindazole
      (7-NI), a preferential neuronal NO synthase (nNOS) inhibitor, injected by
      intracerebroventricular (i.c.v.) route, blocked the development of rapid
      tolerance to ethanol-induced motor incoordination. This effect was prevented by
      i.c.v. injection of L-arginine. The second experiment showed that D-arginine did
      not influence the blockade of tolerance produced by 7-NI. The third experiment
      revealed that i.c.v. injection of 7-NI also blocked the development of tolerance
      to the hypothermic effect of ethanol. These results support the hypothesis that
      nNOS-derived NO participates in the development of rapid tolerance to ethanol.

PMID- 11849823
TI  - Nitric oxide reduces blood pressure in the nucleus tractus solitarius: a real
      time electrochemical study.
AB  - Increasing evidence has demonstrated that nitric oxide (NO) is involved in
      central cardiovascular regulation. In this study, we directly measured
      extracellular NO levels, in real-time, in the nucleus tractus solitarius (NTS) of
      anesthetized cats using Nafion/Porphyrine/o-Phenylenediamine-coated NO sensors.
      We found that local application of L-arginine (L-Arg) induced NO overflow in NTS
      and hypotension. These responses were potentiated in the vagotomized animals.
      Pretreatment with NO synthase (NOS)/guanylate cyclase inhibitor methylene blue,
      1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one or NO scavenger hemoglobin attenuated
      L-Arg-induced hypotension, suggesting that exogenous supplement of NO suppressed
      cardiac functions through the NOS/cyclic guanosine monophosphate mechanism. The
      role of endogenous NO was examined after local application of N(G)-nitro-L
      arginine methyl ester (L-NAME). We found that L-NAME suppressed endogenous NO
      levels in NTS and elicited hypertension and tachycardia. Taken together, our data
      suggest that NO is tonically released in the NTS to inhibit blood pressure.

PMID- 11849824
TI  - Effects of selective cyclooxygenase enzyme inhibitors on lipopolysaccharide
      induced dual thermoregulatory changes in rats.
AB  - The effects of selective cyclooxygenase-1 and cyclooxygenase-2 inhibitors
      (valeryl salicylate and SC-58236, respectively) on Escherichia coli O111:B4
      lipopolysaccharide (LPS)-induced dual thermoregulatory changes and serum tumor
      necrosis factor-alpha elevation were investigated in rats. LPS (50 microg/kg,
      intraperitoneal) produced an initial hypothermia that was then followed by fever.
      Serum tumor necrosis factor-alpha levels elevated at the initial phase of
      hypothermia. Valeryl salicylate injections (20, 40, and 80 mg/kg, subcutaneous
      [s.c.]) completely inhibited hypothermia without any effect on the elevated serum
      tumor necrosis factor-alpha levels and on the subsequent fever. On the other
      hand, SC-58236 injections (10, 20, and 40 mg/kg, s.c.) only partially abolished
      the hypothermia. SC-58236 had no effect on the initiation of fever, however
      completely inhibited the maintenance of fever. The serum tumor necrosis factor
      alpha elevation was not reduced by SC-58236 treatment. The combination of valeryl
      salicylate and SC-58236 also failed to inhibit the initiation of fever. These
      findings suggest that cycloxygenase-1 may have a predominant role for the
      development of LPS-induced hypothermia, but cyclooxygenase-1 does not seem to be
      involved in the mediation of LPS-induced fever. Meanwhile, cyclooxgenase-2 may be
      critical for the late phase rather than the initiation of the fever response in
      rats.

PMID- 11849825
TI  - Spontaneous, low frequency (approximately 2-3 Hz) field activity generated in rat
      ventral hippocampal slices perfused with normal medium.
AB  - This study demonstrates that transverse slices taken from the ventral hippocampus
      of adult rats perfused with a medium of normal ionic composition sustain
      spontaneous periodic field potentials due to the synchronous activity of a
      population of neurons. This ventral hippocampus spontaneous synchronous activity
      (VHSSA) in CA1 stratum pyramidale consisted of positive potentials (approximately
      0.12 mV, 55 ms) occurring at a frequency of 2.8 +/- 0.2 Hz for hours without
      interruption. VHSSA was most frequently observed in slices taken 1-3 mm from the
      ventral end of hippocampus, and was absent in slices taken from tissue more than
      4.5 mm away from it. Stimulation of Schaffer collaterals primed the appearance of
      potentials, which were similar to VHSSA and clearly distinguishable from
      excitatory postsynaptic potentials. In view of the known relative proneness of
      ventral hippocampus to epilepsy, we perfused ventral slices with high-[K(+)](o)
      medium (8 mM). Albeit reduced in amplitude, VHSSA persisted during the high
      [K(+)](o) induced interictal-like epileptiform activity. We could not document
      any temporal relationship between the two phenomena. Low concentrations of the
      antagonist of gamma-amino-butyric acid receptors, type A, bicuculline (2-3
      microM), which enhanced the high-[K(+)](o) induced epileptiform activity,
      reversibly blocked the VHSSA. We conclude that under standard in vitro conditions
      small circuits in the ventral hippocampus are most often and for long periods of
      time engaged in synchronous quasi-rhythmic low-frequency activity, generated
      locally by mechanisms substantially differing from those supporting epileptiform
      discharges.

PMID- 11849826
TI  - Ethanol modifies differently aspartyl- and glutamyl-aminopeptidase activities in
      mouse frontal cortex synaptosomes.
AB  - Aminopeptidase A activity (aspartyl aminopeptidase (AspAP) and glutamyl
      aminopeptidase (GluAP) exerts angiotensinase activity due to its relation to the
      metabolism of angiotensins in the regional brain renin-angiotensin system (RAS).
      This activity may also modify the free amino acid pool through the release of N
      terminal acidic amino acids. Ethanol (EtOH) exerts profound effects on the brain,
      inducing important neurological damages. Our purpose is to study the influence of
      EtOH on AspAP and GluAP activities on basal and K(+)-stimulated conditions, at
      the synapse level. We used mouse frontal cortex synaptosomes and their incubation
      supernatant in a Ca(2+)-containing or Ca(2+)-free artificial cerebrospinal fluid.
      We evaluate the possible contribution of these enzymatic activities on brain
      blood pressure regulation through RAS and/or the free acidic amino acid pool. The
      results obtained are correlated with several parameters of oxidative stress, such
      as free radical generation, lipid peroxidation, and protein oxidation. Under
      basal conditions, in synaptosomes, EtOH inhibits AspAP and GluAP activities
      independently of Ca(2+). In the supernatant, however, EtOH differently modulates
      the two enzyme activities under the various concentrations. Under K(+)-stimulated
      conditions, EtOH inhibits the K(+)-stimulated increase on AspAP and GluAP
      differently depending on the presence or absence of Ca(2+) and the concentration
      of EtOH used. These results invalidate the idea that excess free acidic amino
      acids could be released by AspAP and GluAP to induce neurodegeneration. The
      changes in AspAP and GluAP activities as a consequence of EtOH administration and
      their role in the brain RAS are discussed.

PMID- 11849827
TI  - Analysis of gene expression with cDNA microarrays in rat brain after 7 and 42
      days of oral lithium administration.
AB  - The gene expression profile in rat brain was examined using microarrays in rats
      fed lithium chloride for 7 days (subacute) or 42 days (chronic). Brain lithium
      concentrations were 0.39 mM and 0.79 mM (therapeutically relevant), at 7 and 42
      days, respectively. Of the 4132 genes represented in the microarrays, 25 genes
      were downregulated by at least twofold and none was upregulated after 7 days of
      treatment. Expression of 50 genes was downregulated by at least two-fold at 42
      days, without any being upregulated. Lithium treatment for 7 days did not affect
      at a measurable extent expression of 37 of the 50 genes that were downregulated
      at 42 days. Genes whose expression was changed at 42 days coded for a number of
      receptors, protein kinases, transcription and translation factors, markers of
      energy metabolism, and signal transduction. Thus, chronic lithium at a
      therapeutically relevant concentration reduced expression of a large number of
      genes involved in multiple signaling and other pathways, without increasing
      expression at a comparable extent.

PMID- 11849828
TI  - Neural correlates of perceptual priming of visual motion.
AB  - In two experiments, the temporal dynamics of neural activity underlying
      perceptual priming of visual motion was examined using event-related potentials
      (ERPs) during directional judgments of the apparent motion of two-dimensional
      sine-wave gratings. Compared to perceptually ambiguous motion, unambiguous left-
      or rightward motion was associated with enhanced ERP activity about 300 ms after
      the onset of apparent motion. In the second experiment, ERPs were recorded to two
      successive motion jumps in which an unambiguous motion jump served as a prime for
      a subsequent target motion that was ambiguous. The prime-target time interval was
      varied between 200, 400, and 1000 ms. In a control (motion reversal) condition,
      the two motion jumps were both unambiguous but in opposite directions. Compared
      to the motion reversal condition, motion priming was associated with an
      enhancement of ERP amplitudes at 100 ms and 350 ms following target stimulus
      onset. ERP enhancement was greatest at a short prime-target interval of 200 ms,
      which was also associated behaviorally with the strongest priming. The ERP
      enhancement and behavioral priming were both eliminated at the long 1000 ms prime
      target interval. Functional magnetic resonance imaging (fMRI) data from a subset
      of subjects supported the view that motion priming involves modulation of neural
      responses both in early visual cortex and in later stages of visual processing.

PMID- 11849829
TI  - A modified oddball paradigm "cross-modal delayed response" and the research on
      mismatch negativity.
AB  - A modified oddball paradigm was developed to facilitate the focus of attention
      and to minimize target effects on deviant-related components of auditory and
      visual event-related potentials (ERPs) elicited with long interstimulus
      intervals. Subjects were required to focus on either the visual or auditory
      stimulus in each stimulus block. Deviant-related components were obtained by
      subtracting ERPs of the standard stimulus from that of the deviant stimulus for
      each modality with each stimulus condition. Results showed that auditory mismatch
      negativity (MMN) and a visual early deviant related negativity (DRN1) were
      elicited both when stimuli were attended and unattended. In contrast, N2b and P3
      were produced only under the attended condition. In comparison of attended MMN
      and unattended MMN at three time windows (100-150 ms, 150-200 ms, and 200-250 ms)
      of MMN zone, different scalp distributions were shown, depending on the time
      windows. This result suggests that the attended auditory MMN is a mixed wave,
      consisting of genuine MMN, N2b, and possible P165. The effect of attention on MMN
      may stem from the contamination of these overlapping components. With the present
      paradigm, at least three sensory memory traces have to be maintained
      simultaneously in multiple sensory modalities to support automatic processing.

PMID- 11849830
TI  - Evidence that nitric oxide production increases gamma-amino butyric acid
      permeability of blood-brain barrier.
AB  - Blood-brain barrier permeability (BBB) to the inhibitory neurotransmitter gamma
      amino butyric acid (GABA) was studied in rats following intraperitoneal (i.p)
      injections of GABA alone and in combination with L-Arginine (L-Arg).
      Administration of GABA (600 mg/kg body weight [b. wt.]) alone increased brain
      GABA concentration (33%, p < 0.01), when compared to untreated rats and
      administration of L-Arg (2000 mg/kg b. wt.) alone also increased GABA
      concentration (65%, p < 0.01) in the brain. Moreover, GABA + L-Arg treated brains
      showed a fourfold increase in GABA level (383.3%, p < 0.01) when compared to
      controls. Dose-dependent increase in nitric oxide production was observed 10 min
      after i.p injections of L-Arg (400, 800, 1000, and 2000 mg/kg b. wt.) and a peak
      nitric oxide (NO) production was observed at the dose level of 2000 mg/kg b. wt.
      On the other hand, administration of GABA failed to increase NO production in the
      brain. Rats pretreated (10 min) with a nonspecific nitric oxide synthase (NOS)
      inhibitor N(omega)-nitro-L-Arginine methyl ester (L-NAME, 50 mg/kg b. wt.)
      completely blocked the production of NO induced by L-Arg. In addition, L-NAME
      attenuated GABA entry into the brain after the administration of GABA alone or in
      combination with L-Arg. We conclude that high NO concentrations in the brain
      following L-Arg administration may increase the permeability of BBB to peripheral
      GABA.

PMID- 11849832
TI  - Evaluation of the efficacy of the crude extract of Aloe secundiflora in chickens
      experimentally infected with Newcastle disease virus.
AB  - Two replicate experiments were carried out to verify the efficacy of Aloe species
      (Aloaceae) as used for the control of Newcastle disease (ND) in rural poultry in
      free-range systems among several communities in Tanzania. Four months old local
      chickens free of Newcastle disease antibodies were used. Following inoculation
      with ND virus, body weights, clinical signs, antibody levels and mortality were
      monitored. Results showed that there was reduced mortality rate and the severity
      of clinical signs during the acute phase of the infection in Aloe treated
      chickens compared with the non-treated ones. However, there was no significant
      effect of the Aloe on the antibody levels that were attributed to the recovery of
      the surviving chickens. The findings of this study suggest that Aloe secundiflora
      could be a potential candidate on the management of Newcastle disease in
      chickens. Further studies are in progress to identify the active ingredients of
      A. secundiflora against Newcastle disease virus.

PMID- 11849831
TI  - Ethnobotanical literature survey of medicinal plants in the Dominican Republic
      used for women's health conditions.
AB  - This ethnobotanical literature survey is part of an on-going study in New York
      City investigating Dominican and Chinese healing systems and the herbal
      treatments used for the following women's conditions: uterine fibroids (benign
      tumors of uterine smooth muscle); menorrhagia (excessive uterine bleeding);
      endometriosis (growth of endometrial tissue outside of the uterus); and hot
      flashes (sudden brief sensations of heat commonly experienced during menopause).
      The objectives of this survey were: (1) to search literature on medicinal plants
      used in the Dominican Republic and identify those used for the above listed
      conditions and their symptoms; (2) to compare the use between herbal treatments
      reported in the literature with those prescribed by Dominican healers in New York
      City; and (3) to evaluate the extent to which healers may have changed their use
      of plants in order to adapt to availability in the New York City environment. A
      total of 87 plant species were reported in the Dominican literature for these
      conditions and symptoms. Nineteen species overlapped from the literature survey
      and the fieldwork with Dominican healers in New York City, representing 29%
      (n=65) of the plants prescribed by healers in New York City. This study offers a
      model to investigate changes in plant use as people migrate to urban centers
      where they are surrounded by diverse cultures, healing systems, and new
      environments.

PMID- 11849833
TI  - Heteropterys aphrodisiaca (extract BST0298): a Brazilian plant that improves
      memory in aged rats.
AB  - Literature report is lacking on pharmacological studies of the plant Heteropterys
      aphrodisiaca, endemic to the scrublands of Brazil. The present study was carried
      out to investigate the effects of oral dosing with extract BST0298 from this
      plant, on learning and on memory, in young (3-6-month-old) and aged (20-28-month
      old) rats. The aged animals presented significant memory deficits in both the
      passive avoidance and T-maze left/right discrimination tests. Treatment for 7
      days (50 mg/kg) or 26 days (100 mg/kg) with extract BST0298 restored the memory
      deficits in the passive avoidance test. However, no improvement in memory was
      observed after acute administration of extract BST0298 (100 mg/kg) in aged rats.
      An improvement in learning was also observed in the left/right discrimination
      test in aged rats treated for 109 days with BST0298 at a dose of 50 mg/kg. These
      results suggest that treatment for 7 days or more with H. aphrodisiaca improves
      learning and memory deficits in aged rats.

PMID- 11849834
TI  - Hepatoprotective activity of two plants belonging to the Apiaceae and the
      Euphorbiaceae family.
AB  - The different extracts of Apium graveolens Linn. (Apiaceae) and Croton
      oblongifolius Roxb. (Euphorbiaceae) were tested for their hepatoprotective
      activity against CCl(4) induced hepatotoxicity in albino rats. The degree of
      protection was measured by using biochemical parameters like serum transaminases
      (SGOT and SGPT), alkaline phosphatase, total protein and albumin. The methanolic
      extracts showed the most significant hepatoprotective activity comparable with
      standard drug silymarin. Other extracts namely petroleum ether and acetone also
      exhibited a potent activity.

PMID- 11849835
TI  - Efficacy of crude extract of Aloe secundiflora against Salmonella gallinarum in
      experimentally infected free-range chickens in Tanzania.
AB  - The ethnoveterinary use of Aloe species extract in free-range local chickens
      against fowl typhoid was investigated. Five-months-old local chickens, free of
      antibodies against fowl typhoid were used. The chickens were randomly assorted
      into five groups including pretreated and infected (G1, n=21), infected and
      untreated (G2, n=21), infected and treated (G3, n=21), untreated and uninfected
      (G4, n=10) and treated uninfected (G5, n=10). Groups 1, 2 and 3 were inoculated
      with 5.0 x 10(8) c.f.u/ml of Salmonella gallinarum, following which the chickens
      were monitored for 15 days. There was a delay on the occurrence of the clinical
      signs and reduced severity of the disease in the Aloe treated chickens (G1 and
      G3). The mortality rates were 23.8% (5/21) in G1 (pretreated and infected), 42.8%
      (9/21) in G2 (infected and untreated) and 14.2% (3/21) in G3 (infected and
      treated). Antibody levels were raised among the infected and untreated group (G2)
      while they remained relatively low in the Aloe treated groups (G1 and G3).
      However, there was a sharp increase in the levels of interleukin 6 (IL-6) in the
      Aloe treated groups (G1 and G3) as compared to the untreated group (G2) until day
      9 post-infection. The results of this work indicate that the extract of Aloe
      secundiflora may be used in the control of fowl typhoid in chickens. Studies to
      determine the active ingredients of the plant extract are in progress.

PMID- 11849836
TI  - Determination of antioxidant activity of lichen Cetraria islandica (L) Ach.
AB  - The study was aimed at evaluating the antioxidant activity of aqueous extract of
      C. islandica. The antioxidant activity, reducing power, superoxide anion radical
      scavenging and free radical scavenging activities were studied. The antioxidant
      activity increased with the increasing amount of extracts (from 50 to 500 microg)
      added to linoleic acid emulsion. About 50, 100, 250, and 500 microg of aqueous
      extract of C. islandica showed higher antioxidant activity than 500 microg of
      alpha-tocopherol. The samples showed 96, 99, 100, and 100% inhibition on
      peroxidation of linoleic acid, respectively. On the other hand, the 500 microg of
      alpha-tocopherol showed 77% inhibition on peroxidation on linoleic acid emulsion.
      Like antioxidant activity, the reducing power, superoxide anion radical
      scavenging and free radical scavenging activities of C. islandica depends on
      concentration and increasing with increased amount of sample. The results
      obtained in the present study indicate that C. islandica is a potential source of
      natural antioxidant.

PMID- 11849837
TI  - Effects of propolis from Brazil and Bulgaria on fungicidal activity of
      macrophages against Paracoccidioides brasiliensis.
AB  - Paracoccidioidomycosis is the most important systemic mycosis in Latin America.
      Its etiological agent, Paracoccidoides brasiliensis, affects individuals living
      in endemic areas through inhalation of airborne conidia or mycelial fragments.
      The disease may affect different organs and systems, with multiple clinical
      features, with cell-mediated immunity playing a significant role in host defence.
      Peritoneal macrophages from BALB/c mice were stimulated with Brazilian or
      Bulgarian propolis and subsequently challenged with P. brasiliensis. Data suggest
      an increase in the fungicidal activity of macrophages by propolis stimulation,
      independently from its geographic origin.

PMID- 11849838
TI  - Cytotoxic effect of Argentine medicinal plant extracts on human hepatocellular
      carcinoma cell line.
AB  - Methanolic extracts from Achyrocline satureioides (Dc.) Lam, Aristolochia
      macroura Gomez, Lithraea molleoides (Vell.) Engl., Schinus molle L., unlike those
      from Celtis spinosa Spreng, Chenopodium ambrosioides L., Petiveria alliacea L.,
      and Plantago major L. showed cytotoxic activity against a human hepatocellular
      carcinoma cell line, Hep G2. Schinus molle L. was the most active (IC50=50+/-7
      microg/ml). These results call for further studies of these extracts.

PMID- 11849839
TI  - Protective effects of Polygalae root in experimental TNBS-induced colitis in
      mice.
AB  - In this study, the protective effect of Polygalae root was evaluated in a murine
      model of experimental colitis by intrarectal injection with 2,4,6-trinitrobenzene
      sulfonic acid (TNBS). Polygalae root, given orally at 2, 4 g/kg body weight of
      herbs once a day consecutively for 9 days, could recover the lost body weight and
      decrease the gross rectal bleeding. Polygalae root also reduced the degree of
      inflammation and improved significantly the histological changes such as
      infiltration by polymorphonuclear leukocytes and multiple erosive lesions.
      Furthermore, the cytokine production of intraepithelial lymphocytes was analyzed.
      The results showed that IFN-gamma was increased, but IL-4 was decreased in TNBS
      induced colitis, when those were compared with the sham controls. But the
      administration of Polygalae root to TNBS-induced colitis mice showed lower
      production of IFN-gamma and higher production of IL-4 than the TNBS-induced
      colitis. These results suggest that the protective effects of Polygalae root
      against the TNBS colitis may be associated with the regulation of cytokine
      production of intraepithelial lymphocytes.

PMID- 11849840
TI  - Effect of Acanthopanax senticosus stem on mast cell-dependent anaphylaxis.
AB  - We studied the effect of Acanthopanax senticosus stem (ACPS) on mast cell
      dependent anaphylaxis. ACPS inhibited compound 48/80-induced systemic anaphylaxis
      at a dose of 1.0 g/kg by 50%. ACPS also inhibited passive cutaneous anaphylaxis
      reaction and histamine release from mast cells in a dose-dependent manner,
      respectively. Moreover, ACPS had an inhibitory effect on anti-dinitrophenyl IgE
      induced tumor necrosis factor-alpha (TNF-alpha) production from mast cells. These
      results indicate that ACPS inhibits mast cell-mediated anaphylaxis in vivo and in
      vitro murine model.

PMID- 11849841
TI  - Diuretic effect and mechanism of action of parsley.
AB  - This work provides substantial evidence for the advocated diuretic effect of
      parsley in folk medicine and determines the mechanism of action of the herb. Rats
      offered an aqueous parsley seed extract to drink, eliminated a significantly
      larger volume of urine per 24 h as compared to when they were drinking water.
      These findings were supported by the results of other experiments using an in
      situ kidney perfusion technique which demonstrated also a significant increase in
      urine flow rate with parsley seed extract. This effect was still apparent in
      presence of amiloride, furosemide and in the absence of sodium, but not in the
      absence of potassium, suggesting that the diuretic effect of the herb is mediated
      through an increase in K+ retention in the lumen. Parsley extract, was shown on
      the other hand, to reduce the activity of the Na+-K+ ATPase in both cortex and
      medulla homogenates. Such an inhibition would decrease apical cellular Na+
      reabsorption, lower K+ secretion, increase K+ concentration in the intercellular
      space and consequently would inhibit passive K+ influx across the tight
      junctions. The mechanism of action of parsley seems to be mediated through an
      inhibition of the Na+-K+ pump that would lead to a reduction in Na+ and K+
      reabsorption leading thus to an osmotic water flow into the lumen, and diuresis.

PMID- 11849842
TI  - Screening of antibiotic resistant inhibitors from local plant materials against
      two different strains of Staphylococcus aureus.
AB  - The inhibitory effects of methanolic extracts of 19 Jordanian plants and their
      combinations with seven antibiotics, on the resistance of Staphylococcus aureus
      were checked. Methicillin resistant S. aureus (MRSA), which was isolated from
      patient and a standard strain of S. aureus were used. Our results showed that
      there are variations in the effect of some combinations used on the resistant and
      the standard strains probably due to structural changes. Common results between
      the two strains showed that combinations of gentamicin and chloramphenicol could
      be improved by the use of plant materials, whereas nalidixic acid activity cannot
      be improved when combined with plant materials.

PMID- 11849843
TI  - Antiviral activities of flavonoids and organic acid from Trollius chinensis
      Bunge.
AB  - The flower of Trollius chinensis Bunge is used for treating upper respiratory
      infections, pharyngitis, tonsillitis, and bronchitis in Chinese folk medicine.
      The antiviral activities of the crude extract, total flavonoids, orientin,
      vitexin and proglobeflowery acid isolated from the flowers of T. chinensis
      against parainfluenza type 3 (Para 3) virus were investigated. The results showed
      that the crude extract and total flavonoids exhibited a weak antiviral activity
      against Para 3. Orientin and vitexin demonstrated potent or moderate antiviral
      activity against Para 3. Proglobeflowery acid showed weak antiviral activity
      against Para 3.

PMID- 11849844
TI  - Vasodilator activity of crude methanolic extract of Gentiana kokiana Perr. et
      Song. (Gentianaceae).
AB  - Gentiana kokiana Perr. et Song. is a plant employed in the traditional medicine
      of Tuscany (Italy) as antihypertensive remedy. The aim of this work was to
      evaluate a possible vascular action of the plant and to investigate its mechanism
      of action. The methanolic extract of roots showed an endothelium-independent
      vasodilator activity in aortic rings pre-contracted by norepinephrine (NE) 3
      microM and a marked depression of the contracturant responses induced by KCl and
      caffeine, and by NE, both in Tyrode solution and Ca2+-free Tyrode solution. An
      action on the Ca2+-extracellular influx was discarded, while release or uptake
      mechanisms of the sarcoplasmic reticulum were hypothesized. However, the
      incapacity of cyclopiazonic acid (20 microM), a blocker of Ca2+/ATPase of the
      sarcoplasmic reticulum, to reduce the vasodilator action of the extract allowed
      to exclude the involvement of such a mechanism. A possible involvement of the
      ryanodine-sensitive Ca2+ channels is suggested.

PMID- 11849845
TI  - Anti-oxidant and immunomodulatory properties of seabuckthorn (Hippophae
      rhamnoides)--an in vitro study.
AB  - This study was designed to determine the anti-oxidant and immunomodulatory
      properties of seabuckthorn (Hippophae rhamnoides) using lymphocytes as a model
      system. Chromium(VI) as potassium dichromate was used to induce oxidative damage.
      The production of free radicals by chromium and the ability of alcoholic leaf and
      fruit extracts of seabuckthorn to inhibit the oxidative damage induced by
      chromium was investigated. Addition of chromium (10 microg/ml) to the cells
      resulted in enhanced cytotoxicity, apoptosis, free radical production and
      decreased glutathione (reduced) levels. Chromium also caused a significant
      inhibition of lymphocyte proliferation induced by both lipopolysaccharide and
      concanavalin A. Alcoholic extracts of leaves and fruits of seabuckthorn at a
      concentration of 500 microg/ml were found to inhibit chromium-induced free
      radical production, apoptosis, DNA fragmentation and restored the anti-oxidant
      status to that of control cells. In addition, these extracts also were able to
      arrest the chromium-induced inhibition of lymphocyte proliferation. These
      observations suggest that the alcoholic extracts of leaves and fruits of
      seabuckthorn have marked cytoprotective properties, which could be attributed to
      the anti-oxidant activity.

PMID- 11849846
TI  - Antioxidant activity of flavonoids from Licania licaniaeflora.
AB  - In our screening program for antioxidants with DPPH radical scavenging activity
      we tested several flavonoids isolated from the leaves of Licania licaniaeflora
      (Chrysobalanaceae family) and identified by spectroscopic evidence, particularly
      with 1H and 13C NMR. All the isolated compounds exhibited DPPH radical scavenging
      activity: quercetin derivatives showed the strongest action, while the flavanone
      8-hydroxy-naringenin and kaempferol 3-O-alpha-rhamnoside had the lowest.

PMID- 11849847
TI  - Principles of root bark of Hippocratea excelsa (Hippocrataceae) with
      gastroprotective activity.
AB  - The aqueous and ethanol extracts of the root bark of Hippocratea excelsa HBK.
      Locally known as 'Cancerina', showed an important gastroprotective effect in
      several experimental ulcer models in rats. Fractionation of the methanol extract
      led to four pools of active fractions (F1-F4). Sitosterol-3-O-beta-glucoside,
      beta-sitosterol and (-) epicatechin were isolated from the active fractions and
      showed an important gastroprotective activity (93.4,85.7 and 72.1% of
      gastroprotection, respectively), whereas bismuth subsalicylate, used as positive
      control, showed 46.2% of gastroprotection. A mixture of alpha-amyrin and beta
      amyrin showed 50% of gastroprotection. Friedelin, canophyllal and canophyllol
      were isolated from the active fractions, but they were inactive as
      gastroprotective compounds. These results provide additional support for the
      popular use of this plant as an antiulcer remedy in the Mexican traditional
      medicine.

PMID- 11849848
TI  - Isolation and pharmacological activity of phenylpropanoid esters from Marrubium
      vulgare.
AB  - The isolation and identification of major phenylpropanoid esters from Marrubium
      vulgare: (+) (E)-caffeoyl-L-malic acid 1, acteoside 2, forsythoside B 3,
      arenarioside 4, ballotetroside 5, as well as their anti-inflammatory activity are
      reported for the first time. We evaluated the inhibitory effects of these five
      compounds on cyclooxygenase (Cox) catalysed prostaglandin biosynthesis activity.
      Only the glycosidic phenylpropanoid esters showed an inhibitory activity towards
      the Cox-2 enzyme and three of them: acteoside 2, forsythoside B 3, arenarioside
      4, exhibited higher inhibitory potencies on Cox-2 than on Cox-1. These results
      are of interest, as Cox-2 is mainly associated with inflammation and the Cox-1
      inhibition with adverse side effects often observed with non-steroidal anti
      inflammatory drugs. The occurrence of these phenylpropanoid esters could also
      explain some other pharmacological properties of M. vulgare.

PMID- 11849851
TI  - The effect of completeness of revascularization on event-free survival at one
      year in the ARTS trial.
AB  - OBJECTIVES: We sought to assess the relationship between completeness of
      revascularization and adverse events at one year in the ARTS (Arterial
      Revascularization Therapies Study) trial. BACKGROUND: There is uncertainty to
      what extent degree of completeness of revascularization, using up-to-date
      techniques, influences medium-term outcome. METHODS: After consensus between
      surgeon and cardiologist regarding the potential for equivalence in the
      completeness of revascularization, 1,205 patients with multivessel disease were
      randomly assigned to either bypass surgery or stent implantation. All baseline
      and procedural angiograms and surgical case-record forms were centrally assessed
      for completeness of revascularization. RESULTS: Of 1,205 patients randomized,
      1,172 underwent the assigned treatment. Complete data for review were available
      in 1,143 patients (97.5%). Complete revascularization was achieved in 84.1% of
      the surgically treated patients and 70.5% of the angioplasty patients (p <
      0.001). After one year, the stented angioplasty patients with incomplete
      revascularization showed a significantly lower event-free survival than stented
      patients with complete revascularization (i.e., freedom from death, myocardial
      infarction, cerebrovascular accident and repeat revascularization) (69.4% vs.
      76.6%; p < 0.05). This difference was due to a higher incidence of subsequent
      bypass procedures (10.0% vs. 2.0%; p < 0.05). Conversely, at one year, bypass
      surgery patients with incomplete revascularization showed only a marginally lower
      event-free survival rate than those with complete revascularization (87.8% vs.
      89.9%). CONCLUSIONS: Complete revascularization was more frequently accomplished
      by bypass surgery than by stent implantation. One year after bypass, there was no
      significant difference in event-free survival between surgically treated patients
      with complete revascularization and those with incomplete revascularization, but
      patients randomized to stenting with incomplete revascularization had a greater
      need for subsequent bypass surgery.

PMID- 11849852
TI  - What constitutes optimal surgical revascularization? Answers from the Bypass
      Angioplasty Revascularization Investigation (BARI).
AB  - OBJECTIVES: The study was done to derive the optimum definition of complete
      revascularization in coronary artery bypass surgery. BACKGROUND: "Complete
      revascularization" has been considered the goal of coronary artery bypass
      operations, but various definitions of completeness exist. METHODS: We evaluated
      the Bypass Angioplasty Revascularization Investigation (BARI) surgical results in
      the seven years after operation. Different definitions of completeness of
      revascularization were retrospectively applied to the 1,507 patients in the
      combined randomized/registry group to derive the definition of complete operative
      revascularization with the best discrimination in long-term results between those
      with and without complete revascularization as defined. Four definitions were
      evaluated: 1) traditional complete revascularization with one graft to each major
      diseased artery system; 2) functional complete revascularization with one graft
      to all diseased major or primary segmental vessels; 3) number of distal
      anastomoses greater than, equal to or less than the number of diseased coronary
      segments; and 4) number of distal anastomoses to the major coronary systems equal
      to 1 or greater than 1. RESULTS: No independent survival advantage existed for
      traditional or functional complete revascularization as compared with incomplete
      revascularization. No survival advantage existed for any of the three arms of
      definition 3. For definition 4, seven-year death/myocardial infarction was
      highest (32.9%) when more than one anastomosis was constructed to any non-left
      anterior descending coronary artery (LAD) system (relative risk 1.37, p = 0.03).
      No increased risk was associated with constructing more than one anastomosis into
      the LAD system. CONCLUSIONS: The construction of more than one graft to any
      system other than the LAD appears to confer no long-term advantage, and may
      actually be deleterious.

PMID- 11849853
TI  - In vivo early and mid-term flow-mediated endothelial function of the radial
      artery used as a coronary bypass graft.
AB  - OBJECTIVES: We sought to evaluate the in vivo endothelial function of the radial
      artery (RA) used as a coronary graft. BACKGROUND: The RA is becoming a recognized
      alternative coronary bypass conduit. In vivo endothelial function is a possible
      predictor of long-term performance. METHODS: Sixty consecutive patients underwent
      coronary artery bypass graft surgery (CABG); all received RA and left internal
      mammary artery (LIMA) grafts. Three weeks after CABG, 36 patients underwent
      angiography under basal conditions, during pacing and after intragraft injection
      of glyceryl trinitrate (GTN). Angiography was repeated at six months in 20
      patients. RESULTS: The estimated mean difference of 66 segments of the radial
      graft on the first QCA study was 0.170 mm (95% confidence interval [CI] 0.101 to
      0.258, p < 0.001) between baseline and pacing, and 0.310 mm (CI 0.225 to 0.401, p
      < 0.001) between baseline and GTN. At six months, the differences between
      baseline and pacing and baseline and GTN were 0.112 mm (CI 0.062 to 0.162, p <
      0.001) and 0.274 (CI 0.192 to 0.353, p < 0.001), respectively. The difference
      between baseline values at three weeks and six months was 0.416 mm (CI 0.236 to
      0.603, p < 0.001). In the LIMA segments, the difference between baseline and
      pacing and baseline and GTN were 0.206 mm (CI 0.136 to 0.278, p < 0.001) and
      0.304 mm (CI 0.213 to 0.396, p < 0.001), respectively. At six months, the
      differences between baseline and pacing and baseline and GTN were 0.098 mm (CI
      0.014 to 0.173, p < 0.001) and 0.218 mm (CI 0.130 to 0.298, p < 0.001). The
      difference between baseline values at three weeks and six months was 0.061 mm (CI
      0.064 to 0.176, p > 0.05). CONCLUSIONS: In vivo flow-mediated dilation of the RA
      is comparable to that of pedicled LIMA. The increased dilation both at baseline
      and after pacing at six months represents a time-related improvement in the
      vasomotor function of the RA, which could have implications for its performance
      as a coronary conduit.

PMID- 11849854
TI  - The impact of obesity on the short-term and long-term outcomes after percutaneous
      coronary intervention: the obesity paradox?
AB  - OBJECTIVES: The purpose of this study was to assess the impact of body mass index
      (BMI) on the short- and long-term outcomes after percutaneous coronary
      intervention (PCI). BACKGROUND: Obesity is associated with advanced coronary
      artery disease (CAD). However, the relation between BMI and outcome after PCI
      remains controversial. METHODS: We studied 9,633 consecutive patients who
      underwent PCI between January 1994 and December 1999. Patients were divided into
      three groups according to BMI: normal, BMI between 18.5 and 24.9 (n = 1,923);
      overweight, BMI between 25 and 30 (n = 4,813); and obese, BMI >30 (n = 2,897).
      RESULTS: Obese patients were significantly younger and had consistently worse
      baseline clinical characteristics than normal or overweight patients, with a
      higher incidence of hypertension, diabetes, hypercholesterolemia and smoking
      history (p < 0.0001). Despite similar angiographic success rates among the three
      groups, normal BMI patients had a higher incidence of major in-hospital
      complications, including cardiac death (p = 0.001). At one-year follow-up,
      overall mortality rates were significantly higher for normal BMI patients
      compared with overweight or obese patients (p < 0.0001). Myocardial infarction
      and revascularization rates did not differ among the three groups. By
      multivariate Cox regression analysis, diabetes, hypertension, age, BMI and left
      ventricular function were independent predictors of long-term mortality.
      CONCLUSIONS: In patients with known CAD who undergo PCI, very lean patients (BMI
      <18.5) and those with BMI within the normal range are at the highest risk for in
      hospital complications and cardiac death and for increased one-year mortality.

PMID- 11849855
TI  - Increased plasma levels of the soluble form of Fas ligand in patients with acute
      myocardial infarction and unstable angina pectoris.
AB  - OBJECTIVES: To examine whether the Fas/Fas ligand system is involved in the
      pathogenesis of acute myocardial infarction (AMI), we measured the levels of the
      soluble form of the Fas ligand (sFasL) in the plasma of patients with AMI and
      stable or unstable angina pectoris (AP). BACKGROUND: The Fas ligand (FasL) is
      rapidly cleaved off by a metalloproteinase from the cell membrane to become a
      soluble form as a cytokine. Fas is expressed in most cells, including
      cardiomyocytes, whereas FasL is mainly expressed in inflammatory cells such as
      macrophages, which are greatly accumulated in unstable plaque. METHODS: Thirty
      patients with AMI, 10 patients with unstable AP, 10 patients with stable AP and
      30 control subjects were enrolled in the present study. RESULTS: Plasma sFasL
      levels were significantly elevated on hospital admission in patients with AMI and
      unstable AP, compared with control subjects. Time-course studies revealed that
      plasma sFasL levels rapidly decreased within 3 h and then increased again after
      percutaneous transluminal coronary angioplasty in patients with AMI, but not in
      patients with stable AP. Importantly, the sFasL levels were higher in the
      coronary sinus than in the circulation. In addition, in vitro studies showed that
      the expression of FasL messenger ribonucleic acid was upregulated in mononuclear
      cells isolated from patients with AMI and that hypoxia stimulated the release of
      sFasL from isolated mononuclear cells. CONCLUSIONS: This demonstration of
      elevated levels of sFasL in patients with AMI and unstable AP suggests that
      activation of the Fas/FasL system may play a pathogenic role in AMI and acute
      coronary syndromes.

PMID- 11849856
TI  - Impact of normalized myocardial perfusion after successful angioplasty in acute
      myocardial infarction.
AB  - OBJECTIVES: We sought to evaluate and validate the ability of the angiographic
      myocardial blush grade to risk stratify patients after successful angioplasty in
      acute myocardial infarction (AMI). BACKGROUND: Although epicardial Thrombolysis
      In Myocardial Infarction (TIMI)-3 flow is restored in >90% of patients undergoing
      primary percutaneous coronary intervention (PCI), normal myocardial perfusion may
      be present less frequently and may detrimentally impact survival. METHODS: A
      cohort of 173 consecutive patients undergoing intervention within 24 h of AMI
      onset were studied. High-risk features of this population included failed
      thrombolysis in 39%, cardiogenic shock in 17% and saphenous vein graft culprit in
      11% of patients. RESULTS: Despite the restoration of TIMI-3 flow in 163 (94.2%)
      patients, myocardial perfusion, as evidenced by normal contrast opacification of
      the myocardial bed subtended by the infarct artery (myocardial blush), was normal
      in only 29.4% of patients with TIMI-3 flow following PCI, and in no patient with
      TIMI 0 to 2 flow. In patients in whom TIMI-3 flow was restored, survival was
      strongly dependent on the myocardial perfusion grade; one-year cumulative
      mortality was 6.8% with normal myocardial blush, 13.2% with reduced myocardial
      blush and 18.3% in patients with absent myocardial blush (p = 0.004).
      CONCLUSIONS: Abnormal myocardial perfusion is present in most patients following
      primary or rescue PCI in AMI, despite restoration of brisk epicardial coronary
      flow. In high risk patients achieving TIMI-3 flow after intervention, the
      myocardial blush score may be used to stratify prognosis into excellent,
      intermediate and poor survival. Further study is warranted to examine whether
      adjunctive mechanical or pharmacologic strategies can further improve myocardial
      perfusion and survival of patients with acute myocardial infarction undergoing
      intervention.

PMID- 11849857
TI  - Primary angioplasty reduces the risk of left ventricular free wall rupture
      compared with thrombolysis in patients with acute myocardial infarction.
AB  - OBJECTIVES: This study aimed to evaluate the effect of primary angioplasty (PA)
      over the risk of free wall rupture (FWR) in reperfused acute myocardial
      infarction (AMI). BACKGROUND: It has been suggested that PA reduces the risk of
      FWR compared with thrombolysis. However, few studies have evaluated this issue,
      and there are no data demonstrating this hypothesis. METHODS: A total of 1,375
      patients with AMI treated with PA (n = 762, 55.4%) or thrombolysis (n = 613,
      44.6%) within 12 h after symptoms onset were included. The diagnosis of FWR was
      made either in the presence of sudden death due to electromechanical dissociation
      with large pericardial effusion on an echocardiogram or when demonstrated post
      mortem or at surgery. A multivariable analysis was performed including type of
      reperfusion strategy. RESULTS: The overall incidence of FWR was 2.5% (n = 34):
      1.8% and 3.3% in patients treated with PA and with thrombolysis, respectively (p
      = 0.686). The following characteristics were associated with a higher rate of FWR
      in the univariable analysis: age >70 (5.2% vs. 1.2%, p < 0.001), female gender
      (5.1% vs. 1.8%, p = 0.006), anterior location (3.3% vs. 1.4%, p = 0.020) and
      treatment >2 h after symptoms onset (3.6% vs. 1.7%, p = 0.043). In the
      multivariable analysis, age >70 (odds ratio [OR]: 4.12, 95% confidence interval
      [CI]: 2.04 to 8.62, p < 0.001) and anterior location (OR: 2.91, 95% CI: 1.36 to
      6.63, p = 0.008) were independent risk factors of FWR, whereas treatment with PA
      was an independent protective factor (OR: 0.46, 95% CI: 0.22 to 0.96, p =
      0.0371). CONCLUSIONS: In patients with AMI, PA reduces the risk of FWR in
      comparison with thrombolysis.

PMID- 11849860
TI  - Predictors of aneurysmal formation after surgical correction of aortic
      coarctation.
AB  - OBJECTIVES: We sought to identify the predictors of aneurysmal formation after
      surgical correction of aortic coarctation. BACKGROUND: In 9% of patients,
      aneurysms develop late after corrective surgery of coarctation of the aorta, with
      a 36% mortality rate if left untreated. However, the predictors of postsurgical
      aneurysmal formation are unknown. METHODS: Of 25 aortic aneurysms requiring
      corrective surgery 152 +/- 78 months after the initial coarctation repair, 8 were
      located in the ascending aorta (type A) and 17 at the site of previous repair
      (local type). Seventy-four patients without progression of the aortic diameter
      within 189 +/- 71 months after coarctation repair were used for categorical data
      analysis in an attempt to identify the predictors of postsurgical aneurysmal
      formation. RESULTS: Advanced age at coarctation repair (p = 0.004) and patch
      graft technique (p < 0.0005) independently predicted local aneurysmal formation.
      Type A aneurysm was univariately associated with the presence of a bicuspid
      aortic valve (p = 0.02), advanced age at coarctation repair (p = 0.044) and a
      high preoperative peak systolic pressure gradient of 74 +/- 21 mm Hg (p = 0.041).
      Conversely, multivariate analysis confirmed only the presence of a bicuspid
      aortic valve (p = 0.015) as an independent predictor of type A aneurysm. Receiver
      operating characteristic curve analysis revealed that 72% of patients with a
      postsurgical aneurysm had an operation at age 13.5 years or more, whereas 69%
      with no postsurgical aneurysm had an operation at a younger age. CONCLUSIONS: Use
      of the patch graft technique and late correction of coarctation can predict
      aneurysmal formation at the site of coarctation repair, although patients with a
      bicuspid aortic valve may be at risk for an aneurysm developing in the ascending
      aorta, particularly after late repair of aortic coarctation with high
      preoperative pressure gradients.

PMID- 11849859
TI  - Effects of probucol and pravastatin on common carotid atherosclerosis in patients
      with asymptomatic hypercholesterolemia. Fukuoka Atherosclerosis Trial (FAST).
AB  - OBJECTIVES: This study investigated the effect of reducing serum lipids on
      carotid artery intima-media thickness (IMT) in asymptomatic patients with
      hypercholesterolemia from Fukuoka, Japan. BACKGROUND: Carotid atherosclerosis is
      a strong, independent predictor of morbidity and mortality in patients with
      coronary heart disease (CHD). METHODS: A total of 246 asymptomatic
      hypercholesterolemic patients (mean age 66 years) were randomized to receive
      either probucol (500 mg/day, n = 82) or pravastatin (10 mg/day, n = 83) or to
      enter a control group (diet alone, n = 81); they were followed for two years. The
      change in IMT in the common carotid artery was the primary end point measure, and
      the incidence of major cardiovascular events was the secondary measure. RESULTS:
      Over the two-year period, serum low-density lipoprotein (LDL) cholesterol was
      significantly reduced in the pravastatin group (36%), the probucol group (29%)
      and the control group (12%) (p < 0.0001, p < 0.0001 and p < 0.05, respectively).
      After two years, the probucol and pravastatin groups showed a significant
      reduction in IMT (-13.9% and -13.9% and p < 0.01 and p < 0.01, respectively), but
      there was significant IMT thickening (23.2%; p < 0.05) in the control group.
      Probucol reduced the rate of IMT increase, independently of its reduction of LDL
      or high-density lipoprotein cholesterol. Moreover, there was a significantly
      lower incidence of cardiac events in the probucol group (2.4%) than in the
      control group (13.6%) (p = 0.0136). CONCLUSIONS: Probucol reduced cholesterol
      levels and stabilized plaque, leading to a lower incidence of cardiac events in
      these hypercholesterolemic patients.

PMID- 11849858
TI  - Visualization of coronary atherosclerotic plaques in patients using optical
      coherence tomography: comparison with intravascular ultrasound.
AB  - OBJECTIVES: The aim of this study was to evaluate the feasibility and the ability
      of intravascular optical coherence tomography (OCT) to visualize the components
      of coronary plaques in living patients. BACKGROUND: Disruption of a vulnerable
      coronary plaque with subsequent thrombosis is currently recognized as the primary
      mechanism for acute myocardial infarction. Although such plaques are considered
      to have a thin fibrous cap overlying a lipid pool, imaging modalities in current
      clinical practice do not have sufficient resolution to identify thin (< 65
      microm) fibrous caps. Optical coherence tomography is a new imaging modality
      capable of obtaining cross-sectional images of coronary vessels at a resolution
      of approximately 10 microm. METHODS: The OCT images and corresponding histology
      of 42 coronary plaques were compared to establish OCT criteria for different
      types of plaques. Atherosclerotic lesions with mild to moderate stenosis were
      identified on angiograms in 10 patients undergoing cardiac catheterization.
      Optical coherence tomography and intravascular ultrasound (IVUS) images of these
      sites were obtained in all patients without complication. RESULTS: Comparison
      between OCT and histology demonstrated that lipid-rich plaques and fibrous
      plaques have distinct OCT characteristics. A total of 17 IVUS and OCT image pairs
      obtained from patients were compared. Axial resolution measured 13 +/- 3 microm
      with OCT and 98 +/- 19 microm with IVUS. All fibrous plaques, macrocalcifications
      and echolucent regions identified by IVUS were visualized in corresponding OCT
      images. Intimal hyperplasia and echolucent regions, which may correspond to lipid
      pools, were identified more frequently by OCT than by IVUS. CONCLUSIONS:
      Intracoronary OCT appears to be feasible and safe. Optical coherence tomography
      identified most architectural features detected by IVUS and may provide
      additional detailed structural information.

PMID- 11849861
TI  - Prognostic value of exercise echocardiography in 5,798 patients: is there a
      gender difference?
AB  - OBJECTIVES: This study was designed to determine the effect of gender on the
      prognostic value of exercise echocardiography. BACKGROUND: Limited information
      exists regarding gender differences in prognostic value of exercise
      echocardiography. METHODS: We obtained follow-up (3.2 +/- 1.7 years) in 5,798
      consecutive patients who underwent exercise echocardiography for evaluation of
      known or suspected coronary artery disease. RESULTS: There were 3,322 men (mean
      age 62 +/- 12 years) and 2,476 women (mean age 62 +/- 12 years) (p = 0.7). New or
      worsening wall motion abnormalities developed with exercise in 35% of men and 25%
      of women (p = 0.001). Cardiac events, including cardiac death (107 patients) and
      nonfatal myocardial infarction (148 patients), occurred in 5.3% of men and 3.1%
      of women (p = 0.001). Addition of the percentage of ischemic segments to the
      clinical and rest echocardiographic model provided incremental information in
      predicting cardiac events for both men (chi(2) = 137 to 143, p = 0.014) and women
      (chi(2) = 72 to 76, p = 0.046). By multivariate analysis, exercise
      electrocardiographic and exercise echocardiographic predictors of cardiac events
      in both men and women were workload and exercise wall motion score index. There
      was no significant interaction effect of rest echocardiography (p = 0.79),
      exercise electrocardiography (p = 0.38) or exercise echocardiography (p = 0.67)
      with gender. CONCLUSIONS: Although cardiac events occurred more frequently in
      men, the incremental value of exercise echocardiography was comparable in both
      genders. Of all exercise electrocardiographic and exercise echocardiographic
      variables, workload and exercise wall motion score index had the strongest
      association with outcome. The results of exercise echocardiography have
      comparable implications in both men and women.

PMID- 11849862
TI  - C-reactive protein and angiographic coronary artery disease: independent and
      additive predictors of risk in subjects with angina.
AB  - OBJECTIVES: The objective of this study was to determine the prognostic value of
      C-reactive protein (CRP) independent of coronary angiographic findings.
      BACKGROUND: High sensitivity CRP, a marker of inflammation, predicts risk of
      cardiovascular events. However, it is uncertain whether it remains predictive
      once angiographic findings are considered. METHODS: A total of 2,554 patients
      with angina but without acute myocardial infarction (MI) were studied
      angiographically; 1,848 patients had coronary artery disease (CAD) and 706
      patients did not. Coronary artery disease was quantified in five ways and
      combined for a CAD score. C-reactive protein was measured and patients were
      followed for up to five years for death or MI. RESULTS: C-reactive protein
      correlated with the extent of CAD, but correlation coefficients were low (0.02 to
      0.08). Of angiographic measures, the CAD score best predicted future events
      (hazard ratio [HR] = 1.8 [1.2 to 2.6], p = 0.004, for CAD score > 4). C-reactive
      protein > or = 1.0 mg/dl was predictive in both patients without CAD (HR = 2.3
      [0.9 to 5.5], p = 0.07) and with CAD (HR = 2.1 [1.5 to 3.1], p = 0.0001).
      Multivariate adjustment resulted in little change in HR. C-reactive protein
      retained predictive value within each quintile of CAD score. C-reactive protein
      and CAD independently and additively contributed to the risk prediction: low CRP
      and lowest CAD score was associated with lowest risk, and high CRP and highest
      CAD score was associated with the highest risk, with a 10-fold difference between
      extremes (2.5% vs. 24%). CONCLUSIONS: C-reactive protein correlates with extent
      of CAD, but the degree of correlation is low. Severity/extent of CAD and CRP are
      independent and additive predictors of risk. Therapy should target CRP-associated
      risk as well as angiographically evident stenosis.

PMID- 11849863
TI  - Long-term outcome in patients with apical hypertrophic cardiomyopathy.
AB  - OBJECTIVES: The aim of this study was to describe long-term outcome in patients
      with apical hypertrophic cardiomyopathy (ApHCM) followed in a tertiary referral
      center. BACKGROUND: Apical hypertrophic cardiomyopathy is a relatively rare form
      of hypertrophic cardiomyopathy (HCM), first described in Japan. Initial reports,
      based on a limited number of patients, emphasized the benign nature of this
      condition. METHODS: A retrospective study of 105 patients with ApHCM diagnosed at
      the Toronto General Hospital from 1975 to 2000 was performed. Symptoms, clinical
      findings, mortality and cardiovascular morbidity were analyzed. RESULTS: The mean
      age at presentation was 41.4 +/- 14.5 years. During a mean follow-up of 13.6 +/-
      8.3 years from presentation, cardiovascular mortality was 1.9% (2/105) and annual
      cardiovascular mortality was 0.1%. Overall survival was 95% at 15 years. Thirty
      two patients (30%) had one or more major morbid events, the most frequent being
      atrial fibrillation (12%) and myocardial infarction (10%). Probability of
      survival without morbid events was 74% at 15 years. Three predictors of
      cardiovascular morbidity were identified: age at presentation <41 years, left
      atrial enlargement, and New York Heart Association (NYHA) class > or = II at
      baseline. Forty-four percent of the patients were asymptomatic at the time of
      last follow-up. CONCLUSIONS: Apical hypertrophic cardiomyopathy in North American
      patients is not associated with sudden cardiac death and has a benign prognosis
      in terms of cardiovascular mortality. Nevertheless, one third of these patients
      experience serious cardiovascular complications, such as myocardial infarction
      and arrhythmias. These data are likely to influence the counseling and management
      of patients with ApHCM.

PMID- 11849864
TI  - Removal of cardiodepressant antibodies in dilated cardiomyopathy by
      immunoadsorption.
AB  - OBJECTIVES: The objective of this study was to investigate whether
      immunoadsorption (IA) removes cardiodepressant antibodies from the plasma of
      patients with dilated cardiomyopathy (DCM), as well as to describe their effects
      on isolated rat cardiomyocytes. BACKGROUND: Immunoadsorption induces early
      hemodynamic improvement in patients with DCM. The mechanisms for this improvement
      remain to be elucidated. METHODS: Patients with DCM (n = 11; left ventricular
      ejection fraction < 30%, cardiac index [CI] < 2.5 l/min per m(2)) were treated
      with IA on three consecutive days, with one IA session daily, by application of
      specific antibody columns directed against human immunoglobulin (Ig).
      Immunoadsorption was also conducted on 500 ml of blood taken from nine healthy
      donors (control subjects). After passage of plasma, the IA columns were
      regenerated. Column eluent (CE) was collected and dialyzed (100 kD). Confocal
      laser scanning microscopy was used to analyze the effects of CE on cell
      contraction and on Ca(2+)-dependent fluorescence in isolated, field-stimulated
      adult rat cardiomyocytes loaded with cell-permeable Fluo-3. Immunoprecipitation
      with different preparations of myocardial protein fractions was used for
      characterization of cardiotropic antibodies. RESULTS: During IA, the IgG plasma
      level decreased from 10.7 +/- 0.6 to 2.4 +/- 0.1 g/l (mean +/- SEM), and the CI
      increased from 2.2 +/- 0.1 to 2.7 +/- 0.2 l/min per m(2) (p < 0.01). The CE
      obtained from control subjects did not influence Ca(2+) transients or cell
      shortening of cardiomyocytes. In contrast, in patients with DCM, the CE collected
      during the first regeneration cycle of the first IA session caused an immediate
      and dose-related decrease of Ca(2+) transients (dilution 1:5; -22.7 +/- 5.5%; p <
      0.01) and cell shortening (dilution 1:5; -29.9 +/- 6.0%, p < 0.01). Early
      hemodynamic improvement among the patients correlated with the cardiodepressant
      effect of CE on the isolated cardiomyocytes. Purification of CE by protein A
      adsorption indicated that the cardiodepressant substances are antibodies.
      Immunoprecipitation revealed that the eliminated antibodies are capable of
      binding to various myocardial proteins. CONCLUSIONS: Cardiac autoantibodies play
      a functional role in DCM, and their removal may induce early hemodynamic
      improvement.

PMID- 11849866
TI  - Heart failure in pressure overload hypertrophy. The relative roles of ventricular
      remodeling and myocardial dysfunction.
AB  - OBJECTIVES: We sought to explore the relative contributions of ventricular
      remodeling and myocardial dysfunction to heart failure in pressure overload
      hypertrophy (POH). BACKGROUND: The mechanism that underlies heart failure in POH
      is adverse left ventricular (LV) chamber remodeling or decreased myocardial
      function, or a combination of these. METHODS: Twenty weeks after suprarenal
      aortic banding in rats, animals with POH were classified as those with heart
      failure (POH-HF) or those with no heart failure (POH-NHF). The LV chamber and
      myocardial systolic and diastolic functions were determined from in vivo and ex
      vivo experiments. RESULTS: The LV mass was similar in both POH groups. Chamber
      remodeling in the POH-HF group was characterized by marked LV enlargement with a
      normal relative wall thickness (eccentric remodeling), whereas remodeling in the
      POH-NHF group was characterized by a normal chamber size and increased relative
      wall thickness (concentric remodeling). The LV systolic function, as determined
      in vivo from the end-systolic pressure-diameter relationship and ex vivo from the
      pressure-volume relationship, was lower in the POH-HF group than in the POH-NHF
      and sham-operated control groups. In contrast, myocardial function was similar in
      both POH groups, as determined in vivo from the stress-midwall fractional
      shortening relationship and myocardial systolic stiffness, and ex vivo from the
      slope of the LV systolic stress-strain relationship. The diastolic chamber
      stiffness constant was lower in the POH-HF group than in the POH-NHF group, but
      the myocardial stiffness constant was similar in the two POH groups. CONCLUSIONS:
      The two POH groups differed primarily in their remodeling process, which led to a
      chronically compensated state in one group and to heart failure in the other.
      Hence, heart failure in POH is more closely related to deleterious LV remodeling
      than to depressed myocardial function.

PMID- 11849865
TI  - Physical training modulates proinflammatory cytokines and the soluble Fas/soluble
      Fas ligand system in patients with chronic heart failure.
AB  - OBJECTIVES: We sought to investigate the effects of physical training on
      circulating proinflammatory cytokines and the soluble apoptosis mediators Fas
      (sFas) and Fas ligand (sFasL) in patients with chronic heart failure (CHF).
      BACKGROUND: Recent investigations have shown an overexpression of circulating
      proinflammatory cytokines and soluble apoptosis mediators in patients with CHF,
      which may be related to their exercise intolerance and clinical deterioration.
      METHODS: Plasma levels of tumor necrosis factor-alpha (TNF-alpha), soluble TNF
      receptors I and II (sTNF-RI and sTNF-RII, respectively), interleukin-6 (IL-6),
      soluble IL-6 receptor (sIL-6R), sFas and sFasL were measured in 24 patients with
      stable CHF (New York Heart Association functional class II/III; left ventricular
      ejection fraction 23.2 +/- 1.3%) and in 20 normal control subjects before and
      after a 12-week program of physical training in a randomized, crossover design.
      Functional status of patients with CHF was evaluated by using a cardiorespiratory
      exercise test to measure peak oxygen consumption (VO2max). RESULTS: Physical
      training produced a significant reduction in plasma levels of TNF-alpha (7.5 +/-
      1.0 pg/ml vs. 4.6 +/- 0.7 pg/ml, p < 0.001), sTNF-RI (3.3 +/- 0.2 ng/ml vs. 2.7
      +/- 0.2 ng/ml, p < 0.005), sTNF-RII (2.6 +/- 0.2 ng/ml vs. 2.3 +/- 0.2 ng/ml, p =
      0.06), IL-6 (8.3 +/- 1.2 pg/ml vs. 5.9 +/- 0.8 pg/ml, p < 0.005), sIL-6R (34.0 +/
      3.0 ng/ml vs. 29.2 +/- 3.0 ng/ml, p < 0.01), sFas (5.5 +/- 0.7 ng/ml vs. 4.5 +/-
      0.8 ng/ml, p = 0.05) and sFasL (34.9 +/- 5.0 pg/ml vs. 25.2 +/- 4.0 pg/ml, p <
      0.05), as well as a significant increase in VO2max (16.3 +/- 0.7 ml/kg per min
      vs. 18.7 +/- 0.8 ml/kg per min, p < 0.001). Good correlations were found between
      a training-induced increase in VO2max and a training-induced reduction in levels
      of the proinflammatory cytokine TNF-alpha (r = -0.54, p < 0.01) and the apoptosis
      inducer sFasL (r = -0.57, p < 0.005) in patients with CHF. In contrast, no
      significant difference in circulating cytokines and apoptotic markers was found
      with physical training in normal subjects. CONCLUSIONS: Physical training reduces
      plasma levels of proinflammatory cytokines and the sFas/sFasL system in patients
      with CHF. These immunomodulatory effects may be related to the training-induced
      improvement in functional status of patients with CHF.

PMID- 11849867
TI  - Pressure overload hypertrophy and congestive heart failure. Where is the
      "Achilles' heel"?

PMID- 11849868
TI  - Postexercise blood pressure reduction in elderly hypertensive patients.
AB  - OBJECTIVES: We sought to study: 1) the impact of hemodynamic and left ventricular
      function on short-term postexercise blood pressure reduction in elderly
      hypertensive patients; and 2) the 22-h postexercise effects on ambulatory blood
      pressure in elderly hypertensive patients. BACKGROUND: Although early exercise
      provokes postexercise blood pressure reduction, the mechanisms underlying this
      response are not completely understood. Besides, it is unclear whether the
      reduction in blood pressure after exercise lasts long enough to have clinical
      relevance in elderly hypertensive patients. METHODS: We studied 24 elderly
      hypertensive patients (age 68.9 +/- 1.5 years) and 18 age-matched normotensive
      control subjects (age 68.1 +/- 1.2 years). Cardiac output (carbon dioxide
      rebreathing) and blood pressure (auscultatory) were measured at rest and after a
      45-min period of low-intensity bicycle exercise (50% maximal oxygen uptake) and
      at 15, 30, 60 and 90 min after exercise. Left ventricular function (by Doppler
      echocardiography) was also evaluated. Ambulatory blood pressure monitoring was
      evaluated after 45 min of exercise or 45 min of rest, in a randomized order.
      RESULTS: In the hypertensive patients, exercise provoked a significant reduction
      in blood pressure, cardiac output, stroke volume and left ventricular end
      diastolic volume. It also provoked a significant reduction in systolic, mean and
      diastolic blood pressure during a 22-h period, at daytime and nighttime.
      CONCLUSIONS: The short-term reduction in blood pressure after exercise in elderly
      hypertensive patients is associated with a decrease in stroke volume and left
      ventricular end-diastolic volume. The 22-h postexercise reduction in blood
      pressure demonstrates the clinical relevance of low-intensity exercise in elderly
      hypertensive patients.

PMID- 11849869
TI  - Sympathetic activation markedly reduces endothelium-dependent, flow-mediated
      vasodilation.
AB  - OBJECTIVES: We sought to evaluate whether increased sympathetic outflow may
      interfere with flow-mediated dilation (FMD). BACKGROUND: Endothelial function,
      assessed as FMD, is frequently used as an intermediate end point in intervention
      studies. Many disease states with increased sympathetic tone are also
      characterized by endothelial dysfunction. METHODS: Sixteen healthy volunteers
      underwent FMD studies with and without concomitant sympathetic stimulation. Intra
      arterial nitroglycerin (NTG) infusion was used to assess endothelium-independent
      vasodilation. Pathophysiologically relevant sympathetic stimulation was achieved
      by baroreceptor unloading, using a lower body negative pressure box. In a subset
      of eight volunteers, this protocol was repeated during loco-regional alpha
      adrenergic blockade by intra-arterial infusion of phentolamine (PE). Reactive
      hyperemic flow was assessed with strain-gauge phlethysmography. RESULTS: Overall,
      FMD responses (8.3 +/- 3.4%) were significantly attenuated by concomitant
      sympathetic stimulation (3.6 +/- 3.4%, p < 0.01). Loco-regional alpha-adrenergic
      blockade had no effect on baseline FMD responses (10.7 +/- 4.7%), whereas the
      attenuation by sympathetic stimulation was abolished completely during PE co
      infusion (11.5 +/- 3.3%). During intra-arterial NTG infusions, arterial diameters
      relative to baseline were not significantly different between the four possible
      stages. CONCLUSIONS: Sympathetic stimulation, at a clinically relevant range,
      significantly impairs the FMD response by an alpha-adrenergic mechanism.

PMID- 11849870
TI  - Is electrical stimulation during administration of catecholamines required for
      the evaluation of success after ablation of atrioventricular node re-entrant
      tachycardias?
AB  - OBJECTIVES: The purpose of this study was to answer the question of whether
      stimulation after administration of catecholamines is mandatory for identifying
      unsuccessful ablations of atrioventricular node re-entrant tachycardia (AVNRT).
      BACKGROUND: The success of radiofrequency (RF) catheter ablation in AVNRT is
      confirmed in many centers by noninducibility of tachycardias during stimulation
      after the administration of catecholamines. METHODS: A total of 131 patients (81
      women and 50 men; mean age 53.6 +/- 13.7 years [range 20 to 77]) were studied.
      Electrical stimulation was performed without and with the beta-adrenergic amine
      Orciprenaline (metaproterenol) before and after RF catheter ablation. RESULTS: In
      100 patients (76.3%; confidence interval [CI] 68.1% to 83.3%) an AVNRT was
      inducible without administration of Orciprenaline. Thirty minutes after the
      initially successful ablation in 95 patients, tachycardia was inducible in none
      of these patients, not even after Orciprenaline administration. In the 31
      patients (23.7%; CI 16.7% to 31.9%) in whom there was no tachycardia inducible
      before ablation, Orciprenaline was given, and the stimulation protocol was
      repeated. In only five patients (3.8%; CI 1.3% to 8.7%) was there still no
      tachycardia inducible. After an initially successful ablation in the 26 patients
      who had inducible tachycardias with Orciprenaline before ablation, no tachycardia
      could be re-induced. After Orciprenaline, the tachycardia was inducible again in
      only one patient. CONCLUSIONS: Only patients who require catecholamines for
      tachycardia induction before ablation need catecholamines for control of the
      success of the ablation of AVNRT.

PMID- 11849871
TI  - Cardiac calcification in adult hemodialysis patients. A link between end-stage
      renal disease and cardiovascular disease?
AB  - OBJECTIVES: We sought to determine clinical and laboratory correlates of
      calcification of the coronary arteries (CAs), aorta and mitral and aortic valves
      in adult subjects with end-stage renal disease (ESRD) receiving hemodialysis.
      BACKGROUND: Vascular calcification is known to be a risk factor for ischemic
      heart disease in non-uremic individuals. Patients with ESRD experience
      accelerated vascular calcification, due at least in part to dysregulation of
      mineral metabolism. Clinical correlates of the extent of calcification in ESRD
      have not been identified. Moreover, the clinical relevance of calcification as
      measured by electron-beam tomography (EBT) has not been determined in the ESRD
      population. METHODS: We conducted a cross-sectional analysis of 205 maintenance
      hemodialysis patients who received baseline EBT for evaluation of vascular and
      valvular calcification. We compared subjects with and without clinical evidence
      of atherosclerotic vascular disease and determined correlates of the extent of
      vascular and valvular calcification using multivariable linear regression and
      proportional odds logistic regression analyses. RESULTS: The median coronary
      artery calcium score was 595 (interquartile range, 76 to 1,600), values
      consistent with a high risk of obstructive coronary artery disease in the general
      population. The CA calcium scores were directly related to the prevalence of
      myocardial infarction (p < 0.0001) and angina (p < 0.0001), and the aortic
      calcium scores were directly related to the prevalence of claudication (p =
      0.001) and aortic aneurysm (p = 0.02). The extent of coronary calcification was
      more pronounced with older age, male gender, white race, diabetes, longer
      dialysis vintage and higher serum concentrations of calcium and phosphorus. Total
      cholesterol (and high-density lipoprotein and low-density lipoprotein
      subfractions), triglycerides, hemoglobin and albumin were not significantly
      related to the extent of CA calcification. Only dialysis vintage was
      significantly associated with the prevalence of valvular calcification.
      CONCLUSIONS: Coronary artery calcification is common, severe and significantly
      associated with ischemic cardiovascular disease in adult ESRD patients. The
      dysregulation of mineral metabolism in ESRD may influence vascular calcification
      risk.

PMID- 11849873
TI  - Crosstalk of endothelin-1 and platelet-derived growth factor in cardiac allograft
      arteriosclerosis.
AB  - OBJECTIVES: In this study, we investigated the crosstalk of endothelin-1 (ET-1)
      and platelet-derived growth factor (PDGF) in coronary artery smooth muscle cell
      (SMC) proliferation in the rat cardiac allograft model. BACKGROUND: Previous
      studies have suggested an independent role of ET-1 and PDGF in the development of
      cardiac allograft arteriosclerosis (i.e., chronic rejection). METHODS:
      Heterotopic heart transplantations were performed from Dark Agouti to Wistar
      Furth rats. Grafts were harvested after five days in an acute rejection model and
      after 60 days in a chronic rejection model. In the in vitro part of the study,
      SMC proliferation and migration were quantitated, as well as messenger
      ribonucleic acid (mRNA) levels of ET-1 and PDGF ligands and receptors after
      growth factor stimulation. RESULTS: Acute rejection induced both ET-1 receptors
      in the arterial wall. On linear regression analysis of chronically rejecting
      cardiac allografts, a strong correlation between intimal thickening and
      immunoreactivity of ET-1 and ET receptors A and B (ET(A) and ET(B)) in the
      arterial walls was observed. Treatment with Bosentan, a mixed ET-1 receptor
      antagonist, significantly reduced the incidence and intensity of arteriosclerotic
      lesions in rat cardiac allografts, as well as total intragraft ET(A) and ET(B)
      mRNA expression and intimal cell ET-1 and receptor immunoreactivity. This was
      associated with significantly reduced intragraft PDGF beta-receptor (PDGF-Rbeta)
      mRNA expression. In contrast, CGP 53716, a protein tyrosine kinase inhibitor
      selective for the PDGF receptor, did not reduce intragraft ET-1, ET(A) or ET(B)
      mRNA expression. In rat coronary artery SMC cultures, ET-1 stimulation
      significantly upregulated PDGF-Ralpha and -Rbeta mRNA expression and augmented
      PDGF-BB-mediated SMC proliferation as well as PDGF-AB- and PDGF-BB-mediated SMC
      migration. CONCLUSIONS: Our results suggest that the ET-1/PDGF-Rbeta/PDGF-BB axis
      may operate in SMC migration and proliferation in cardiac allograft
      arteriosclerosis, thus explaining the marked beneficial effects of blocking the
      signaling downstream of ET-1 receptors.

PMID- 11849872
TI  - Bedside quantification of atherosclerosis severity for cardiovascular risk
      stratification: a prospective cohort study.
AB  - OBJECTIVES: We sought to assess the ability of a new noninvasive method to
      quantify atherosclerosis severity and to examine its power to predict
      cardiovascular events. BACKGROUND: Drug prevention of cardiovascular events is
      effective but costly, leading to a debate about who should receive this
      treatment. Patient selection is often based on surrogate markers, but
      quantification of atherosclerosis severity is desirable. METHODS: Atherosclerosis
      severity was quantified by determination of specific aortic wall elastance in
      transthoracic echocardiography, applying the biomechanics of pulse wave
      propagation. After validating the method in 52 patients by measuring aortic
      plaque burden in transesophageal echo directly, another 336 patients were
      prospectively studied by monitoring atherosclerotic events at one year and
      comparing the results with conventional risk stratification. RESULTS: Specific
      aortic elastance was well correlated with plaque burden (p < 0.0001) and largely
      independent of confounding variables. Specific aortic elastance predicted the
      primary end point of "atherosclerotic death, myocardial infarction or stroke" at
      one year (p < 0.0002). Event rate at one year in the lowest specific elastance
      tertile was 1.8% (CI 0.0% to 4.3%), in the middle tertile 5.4% (CI 1.1% to 9.7%)
      and in the highest tertile 12.7% (CI 6.3% to 19%). Secondary end points supported
      these findings. Stepwise multivariate analysis identified specific aortic
      elastance, prior atherosclerotic events and left ventricular ejection fraction as
      independent risk predictors. Specific elastance was of incremental value to
      clinically identified variables. CONCLUSIONS: Bedside measurement of specific
      aortic elastance allows assessment of atherosclerosis severity. It predicts the
      risk for future atherosclerotic events beyond conventional risk factors,
      promising better targeting of pharmacologic prevention and improved cost
      effectiveness.

PMID- 11849874
TI  - High levels of fatty acids delay the recovery of intracellular pH and cardiac
      efficiency in post-ischemic hearts by inhibiting glucose oxidation.
AB  - OBJECTIVES: This study was designed to determine if the fatty acid-induced
      increase in H(+) production from glycolysis uncoupled from glucose oxidation
      delays the recovery of intracellular pH (pH(i)) during reperfusion of ischemic
      hearts. BACKGROUND: High rates of fatty acid oxidation inhibit glucose oxidation
      and impair the recovery of mechanical function and cardiac efficiency during
      reperfusion of ischemic hearts. METHODS: pH(i) was measured by 31P nuclear
      magnetic resonance spectroscopy in isolated working rat hearts perfused in the
      absence (5.5 mmol/l glucose) or presence of 1.2 mmol/l palmitate
      (glucose+palmitate). Glycolysis and glucose oxidation were measured using [5-3H/U
      14C]glucose. RESULTS: When glucose+palmitate hearts were subjected to 20 min of
      no-flow ischemia, recoveries of mechanical function and cardiac efficiency were
      significantly impaired compared with glucose hearts. Glucose oxidation rates were
      significantly lower in glucose+palmitate hearts during reperfusion compared with
      glucose hearts, whereas glycolysis rates were unchanged. This resulted in an
      increase in H(+) production from uncoupled glucose metabolism, and a decreased
      rate of recovery of pH(i) in glucose+palmitate hearts during reperfusion compared
      with glucose-perfused hearts. Dichloroacetate (3 mmol/l) given at reperfusion to
      glucose+palmitate hearts resulted in a 3.2-fold increase in glucose oxidation, a
      35% +/- 3% decrease in H(+) production from glucose metabolism, a 1.7-fold
      increase in cardiac efficiency and a 2.2-fold increase in the rate of pH(i)
      recovery during reperfusion. CONCLUSIONS: A high level of fatty acid delays the
      recovery of pH(i) during reperfusion of ischemic hearts because of an increased
      H(+) production from glycolysis uncoupled from glucose oxidation. Improving the
      coupling of glucose metabolism by stimulating glucose oxidation accelerates the
      recovery of pH(i) and improves both mechanical function and cardiac efficiency.

PMID- 11849876
TI  - Decoy oligodeoxynucleotide against activator protein-1 reduces neointimal
      proliferation after coronary angioplasty in hypercholesterolemic minipigs.
AB  - OBJECTIVES: We sought to demonstrate, in an appropriate animal model, that co
      medication with a transcription factor-blocking agent limits restenosis after
      percutaneous transluminal coronary angioplasty (PTCA). BACKGROUND: Enhanced
      synthesis in the vessel wall of endothelin-1 (ET-1), a powerful co-mitogen for
      vascular smooth muscle cells, appears to be one mechanism that promotes
      restenosis after PTCA. Deformation-induced expression of prepro-ET-1 is governed
      by the transcription factor, activator protein-1 (AP-1). METHODS: An anti-AP-1
      decoy oligodeoxynucleotide (dODN) strategy was devised in which the dODN
      containing solution (20 nmol) was administered locally through a Dispatch
      catheter into the coronary arteries of hypercholesterolemic minipigs at the time
      of PTCA (AVE-GFX stent). RESULTS: Treatment with an AP-1 dODN, mimicking the
      consensus binding site of the transcription factor, significantly reduced
      neointimal formation in the coronary arteries of hypercholesterolemic minipigs (n
      = 10 to 12), compared with vehicle-treated coronary arteries, after four weeks of
      follow-up (neointimal area 2.64 +/- 0.33 vs. 4.81 +/- 1.04 mm(2) [mean +/- SEM];
      p < 0.05). This effect was maintained after eight weeks (neointimal area 2.04 +/-
      0.22 mm(2); n = 3) and correlated with a reduction in both nuclear translocation
      of AP-1 and ET-1 synthesis in the vessel wall 48 h after PTCA (n = 4). In
      contrast, an AP-1 mutant dODN, to which the transcription factor does not bind,
      showed no effect on neointimal formation at either time point (n = 3 to 7).
      Moreover, a consensus dODN directed against CCAAT/enhancer binding protein
      (C/EBP), another deformation-sensitive transcription factor, did not
      significantly affect neointimal formation after four weeks (n = 3). CONCLUSIONS:
      These findings demonstrate the feasibility, efficacy and specificity of the anti
      AP-1 dODN approach to the treatment of restenosis, which principally but not
      exclusively targets deformation-induced ET-1 synthesis in the vessel wall.
      Provided that these findings can be extrapolated to the situation of patients
      with coronary artery disease, the observed extent of the inhibitory effect of the
      AP-1 dODN treatment suggests that this co-medication may greatly reduce the
      incidence of in-stent restenosis.

PMID- 11849875
TI  - Influence of injection site, microvascular pressure and ultrasound variables on
      microbubble-mediated delivery of microspheres to muscle.
AB  - OBJECTIVES: Our objective was to test the hypothesis that the ultrasound pulsing
      interval (PI), microbubble injection site and microvascular pressure
      significantly influence the transport of 100-nm microspheres to muscle through
      extravasation sites created by the destruction of microbubbles with ultrasound.
      BACKGROUND: Microbubbles show promise as targeted drug and gene delivery agents;
      however, designing optimal microbubble-based therapies will require an
      understanding of the factors that influence the transport of microbubble
      delivered, gene-bearing vehicles to tissue. METHODS: Ultrasound at 1 MHz, with a
      peak negative pressure amplitude of 0.75 MPa, was applied to microbubbles and 100
      nm microspheres in exteriorized rat spinotrapezius muscle. Ultrasound PIs of 1,
      3, 5 and 10 s, arterial microsphere injection times of 10 or 40 s and arterial
      versus venous injection sites were tested. RESULTS: Extravasation point creation
      and microsphere delivery were greatest when the ultrasound PI was 5 or 10 s. No
      significant differences in extravasation point creation or microsphere delivery
      were observed with arterial versus venous microbubble injection, but a trend
      toward increased microsphere delivery with arterial injection may exist.
      Decreasing the arterial injection time from 40 to 10 s increased microvascular
      pressure, which, in turn, substantially enhanced microsphere transport to tissue,
      without a concomitant increase in the number of extravasation points.
      CONCLUSIONS: The ultrasound PI and microvascular pressure significantly influence
      the creation of extravasation points and the transport of microspheres to tissue.
      These factors may be important in designing and optimizing contrast ultrasound
      based therapies.

PMID- 11849877
TI  - President's page: fighting terrorism: our role as physicians.

PMID- 11849878
TI  - Transient left ventricular apical ballooning without coronary artery stenosis: a
      form of stunning-like phenomenon?

PMID- 11849880
TI  - Anasarca and low electrocardiogram voltage.

PMID- 11849882
TI  - Pulse wave reflection in pulmonary hypertension.

PMID- 11849885
TI  - Scopolamine?

PMID- 11849887
TI  - Commentary: Pediatric dermatology, part II.

PMID- 11849888
TI  - Acute hemorrhagic edema of infancy (AHEI).

PMID- 11849889
TI  - Disorders of pigmentation in infants and children.

PMID- 11849890
TI  - Vascular reactions in children.

PMID- 11849891
TI  - Disorders of hair in infants and children other than alopecia.

PMID- 11849892
TI  - Pediatric drug allergy.

PMID- 11849893
TI  - Epidemiology of common parasitic infections of the skin in infants and children.

PMID- 11849894
TI  - Diagnosis and management of nevi and cutaneous melanoma in infants and children.

PMID- 11849895
TI  - Cutaneous manifestation of internal diseases in infants and children.

PMID- 11849896
TI  - Mucocutaneous manifestations of viral diseases in children.

PMID- 11849898
TI  - Pediculosis and resistance: the perennial problem.

PMID- 11849897
TI  - Skin manifestations of HIV-1 infection in children.

PMID- 11849899
TI  - Optimal treatment of head lice: is a no-nit policy justified?

PMID- 11849901
TI  - Second World Congress of the International Academy of Cosmetic Dermatology
      (IACD). Rio de Janeiro, Brazil, November 9-11, 2000.

PMID- 11849902
TI  - Reductions in non-fatal overdose after drug misuse treatment: results from the
      National Treatment Outcome Research Study (NTORS).
AB  - Few studies have reported changes in rates of overdose after drug misuse
      treatment. This paper investigates changes in non-fatal overdose between
      treatment intake and 1 year follow-up among a sample of 753 clients recruited to
      the National Treatment Outcome Research Study (NTORS). A relatively high rate of
      overdose (15%) was reported during the 3 months prior to treatment. Variables
      predictive of overdose at intake to treatment included injecting, frequency of
      benzodiazepine and cocaine use, quantity of alcohol consumption, and levels of
      anxiety. At 1 year follow-up, the rate of non-fatal overdose had fallen to 6%.
      Reduced rates of non-fatal overdose were found for clients treated in both
      residential and community treatment settings. Reductions in overdose were linked
      to improvements in frequency of drug use and lower rates of injecting. Clients
      who overdosed at follow-up showed no improvements in their substance use, except
      for frequency of crack cocaine use. The risk of non-fatal overdose at 1 year was
      associated with injecting and multiple drug use. These findings support the view
      that treatment an important role can play in reducing deaths among drug misusers.

PMID- 11849903
TI  - Selecting data sources for substance abuse services research.
AB  - In this article we discuss the strengths and weaknesses of using different types
      of data sources for alcohol and drug abuse services research. To do this, we
      describe four types of data sources used in substance abuse services research:
      surveys of organizations, medical records, claim and encounter data and program
      level administrative data. For each, we outline where to obtain data, how each
      type has been used, and the advantages and challenges. This overview should allow
      investigators to think more critically about the datasets they now use; providers
      to understand the types of data sources most appropriate for specific research
      questions so as to participate more fully in research; and policy makers to
      interpret correctly results based on different types of data. Moreover, it should
      foster better communication among these stakeholders in collaborative projects to
      improve the effectiveness of services for people with addictions.

PMID- 11849904
TI  - A brief intervention for hazardous drinkers in a needle exchange program.
AB  - Active injection drug users (IDUs) who are also hazardous alcohol users are at
      particularly high risk for HIV transmission due to sharing of injection
      equipment. We recruited AUDIT-positive injectors from the Providence, RI needle
      exchange program for a randomized clinical trial testing the effect of a brief
      motivational intervention (MI) on frequency of injection-related HIV risk
      behavior (IRRB). HIV drug risk behavior was measured as the number of days on
      which subjects reported sharing works using the 30-day Timeline Followback
      Method. Overall, 109 subjects reported a mean reduction of IRRB days of 9.1 days
      from baseline to 6-month follow-up (p <.001). When compared to controls, there
      was a trend in reduction of IRRB days to zero at follow-up for MI subject (OR =
      2.1; 95% CI = 0.9-4.5), and strongly significant reductions in IRRB days across a
      range of alternative improvement thresholds. Results from this study demonstrate
      that MI reduces drug-related HIV risk behaviors among active IDUs. As a brief
      intervention, MI may be a useful adjunct to existing services intended to reduce
      harm.

PMID- 11849905
TI  - Prognosis of older patients in mixed-age alcoholism treatment programs.
AB  - Older patients were compared with matched groups of younger and middle-aged
      patients in inpatient alcohol treatment programs (N=432 in each age group).
      Compared with other patients, older patients had poorer physical health and lower
      cognitive status at treatment entry, but they were drinking less and reported
      fewer drinking-related problems, fewer psychological symptoms, more social
      support, more adaptive coping, and fewer barriers to abstinence. Older patients
      had positive views of the programs and, except for less family therapy and
      problem-focused counseling, received comparable treatment to that received by
      other patients. At discharge, older patients showed significant change in most
      areas targeted for treatment. Better initial status was the strongest predictor
      of better discharge functioning. Patients with higher cognitive functioning and
      stronger treatment motivation and those who experienced more interpersonal
      support and who received more specialized treatment services showed better-than
      expected improvement. The age groups showed similar outcomes, prognostic factors,
      and response to different treatment orientations.

PMID- 11849906
TI  - Reduced-risk drinking as a treatment goal: what clinicians need to know.
AB  - Reduced-risk drinking as a treatment goal for clients with alcohol problems has
      received limited acceptance in the United States. The majority of literature
      addressing reduced-risk drinking has focused on debates between proponents of
      traditional abstinence treatment and those supporting nonabstinence treatment.
      Proportionately little attention has been given to objective consideration of the
      potential advantages of integrating both abstinence and nonabstinence goals as
      part of a comprehensive continuum of treatment for clients with alcohol problems.
      Further, there is a lack of guidelines available to assist clinicians in treating
      and supporting clients with nonabstinence goals. The purpose of this article is
      to review the potential advantages of reduced-risk drinking for clients with
      alcohol problems and to forward strategies designed to assist clinicians in
      safely treating clients who wish to reduce rather than abstain from drinking
      alcohol. Current gaps in the literature and implications for future research are
      identified.

PMID- 11849908
TI  - Practical aspects of lyophilization using non-aqueous co-solvent systems.
AB  - Non-aqueous co-solvent systems have been evaluated for their potential use in the
      freeze-drying of pharmaceutical products. The advantages of using these non
      aqueous solvent systems include: increased drug wetting or solubility, increased
      sublimation rates, increased pre-dried bulk solution or dried product stability,
      decreased reconstitution time, and enhancement of sterility assurance of the pre
      dried bulk solution. Conversely, the potential disadvantages and issues which
      must be evaluated include: the proper safe handling and storage of flammable
      and/or explosive solvents, the special facilities or equipment which may be
      required, the control of residual solvent levels, the toxicity of the remaining
      solvent, qualification of an appropriate GMP purity, the overall cost benefit to
      use of the solvent, and the potential increased regulatory scrutiny. The co
      solvent system that has been most extensively evaluated was the tert
      butanol/water combination. The tert-butanol possesses a high vapor pressure,
      freezes completely in most commercial freeze-dryers, readily sublimes during
      primary drying, can increase sublimation rates, and has low toxicity. This co
      solvent system has been used in the manufacture of a marketed injectable
      pharmaceutical product. When using this solvent system, both formulation and
      process control required optimization to maximize drying rates and to minimize
      residual solvent levels at the end of drying. Other co-solvent systems which do
      not freeze completely in commercial freeze-dryers were more difficult to use and
      often resulted in unacceptable freeze-dried cakes. Their use appears limited to
      levels of not more than 10%.

PMID- 11849909
TI  - Biopharmaceuticals and biotechnology medicines: an issue of nomenclature.
AB  - Over the past two decades terms such as 'biopharmaceuticals' and 'biotechnology
      medicines' have crept into the pharmaceutical vocabulary. Such terms often have
      different meanings for different people and it is perhaps time that they were
      more formally defined.

PMID- 11849910
TI  - Loading into and electro-stimulated release of peptides and proteins from
      chondroitin 4-sulphate hydrogels.
AB  - Chondroitin 4-sulphate (CS) hydrogels were examined as potential matrices for the
      electro-controlled delivery of peptides and proteins. A CS hydrogel, cross-linked
      with ethylene glycol diglycidyl ether, and with a swelling ratio of 20, was used
      to study the influence of molecular size and shape of guest molecules on loading
      and release rates. Three positively charged molecules of different molecular
      weights (vasopressin MW 1084, aprotinin MW 6512 and lysozyme MW 14,400), and one
      negatively charged protein (bovine serum albumin MW 67,000) were used as model
      solutes. The hydrogels were loaded by equilibrium swelling. As a result, the
      three positively charged peptide and proteins were found to be concentrated in
      the gels, most likely due to ionic attraction between the negative charges in the
      gel polymeric backbone and the positively charged solutes. No such concentration
      of solute in the gel was seen for the negatively charged albumin. The latter is
      presumably loaded passively by diffusing in the water phase of the gel. The
      loading efficiency (indicated by the loading rate and the total amount of solute
      loaded in the gel) was found to increase with decreasing molecular size of
      solute. Electro-stimulated release of the loaded peptide and proteins was
      followed for 3 h during which an electric field was applied in pulses of 5 V
      (pulse duration and pulse interval were both of 20 min). The release of lysozyme
      and aprotinin from CS hydrogels responded to electrical pulses. On the other
      hand, vasopressin and albumin were largely released by passive diffusion and
      their release could not be electrically controlled. This work shows that the size
      of the guest molecule is an important parameter when electrically-stimulated drug
      release is desired, but further work obviously needs to be carried out with a
      larger range of molecular weights and conformations.

PMID- 11849911
TI  - Nanoparticles in plant extracts: influence of drugs on the formation of
      nanoparticles and precipitates in black tea infusions.
AB  - The influence of the neuroleptics fluphenazine and promethazine on the formation
      of nanoparticles in aqueous tea infusions was investigated using photon
      correlation spectroscopy. Formation of nanoparticles and of precipitates was
      observed in decaffeinated tea and caffeine-containing tea. The amount of drug in
      the nanoparticle fraction was determined at different starting concentrations
      using high-performance liquid chromatography. In the case of fluphenazine,
      between 8 and 30% are assigned to the nanoparticles fraction, in the case of
      promethazine between 30 and 56%. The concentration of free active principle is
      reduced by about 99% for fluphenazine or by about 90% for promethazine. A loss of
      pharmacological activity of the neuroleptics is probable. The addition of
      promethazine to infusions of caffeine containing tea resulted in the formation of
      nanoparticles with a small size distribution; their mean size was comparable to
      the diameter of nanoparticles in pure tea infusions. In the case of fluphenazine
      the mean particle size grew with increasing concentration. Adding promethazine to
      infusions of decaffeinated tea resulted in the formation of nanoparticles with a
      broad size distribution. Two different size classes were formed after addition of
      fluphenazine. Caffeine and neuroleptics both take part in the formation of
      nanoparticles in caffeine containing tea. The particles were visualized using
      scanning electron microscopy. Molecular modelling calculations were performed to
      investigate probable geometries between neuroleptics and thearubigins.

PMID- 11849912
TI  - In vitro simulation of food effect on dissolution of deramciclane film-coated
      tablets and correlation with in vivo data in healthy volunteers.
AB  - The in vitro dissolution profiles of deramciclane 30 mg film-coated tablets, an
      acid-labile new 5-HT receptor antagonist, were studied under simulated fasting
      and fed conditions. Artificial gastric juice with pH adjusted to that of fasting
      conditions was applied either alone or after adding different dietary components.
      The use of the USP dissolution apparatus II (paddle method) showed that the
      presence of dietary components has markedly affected the amount of unchanged drug
      dissolved. As a similar tendency had been observed in food-effect studies in
      healthy volunteers, cumulative area under the curve (AUC(cum)) for both fed and
      fasting conditions were compared and an in vitro--in vivo correlation (IVIVC) was
      evaluated. A linear relationship was established between logarithmic in vivo
      blood sampling time and in vitro dissolution time assigned to equal AUC(cum)
      ratios (AUC(cum, fed)/AUC(cum, fasting)). Despite its limitations, in vitro
      modelling of in vivo conditions might help provide a base for predicting in vivo
      drug behaviour.

PMID- 11849913
TI  - Cyclodextrin complexation: influence on the solubility, stability, and
      cytotoxicity of camptothecin, an antineoplastic agent.
AB  - The solubility of camptothecin (CPT), a highly potent antineoplastic agent, as a
      function of different concentrations of cyclodextrins (alpha-cyclodextrin, alpha
      CD; beta-cyclodextrin, beta-CD; and gamma-cyclodextrin, gamma-CD; hydroxypropyl
      beta-cyclodextrin, HP-beta-CD; and randomly substituted dimethyl-beta
      cyclodextrin, RDM-beta-CD, and dimethyl-gamma-cyclodextrin, RDM-beta-CD) in 0.02
      N HCl solution at 25 degrees C was investigated. The results showed a linear
      increase in the solubility of CPT with increasing concentration of CDs. The
      apparent stability constants (K(c)) for the CPT complexes with alpha-CD, beta-CD,
      gamma-CD, HP-beta-CD, RDM-beta-CD, and RDM-gamma-CD were 188, 266, 73, 160, 910,
      and 40.6 M(-1), respectively, suggesting that RDM-beta-CD afforded the most
      stable complex. At a 25% w/v concentration of RDM-beta-CD, the solubility of CPT
      was 228.45 +/- 8.45 microg/ml, about 171 times higher than that in 0.02 N HCl.
      The stability of CPT in pH 7.4 buffer at 25 degrees C also increased linearly
      with an increase in the concentration of RDM-beta-CD. The observed pseudo-first
      order hydrolysis rate constants (k(obs)) for the free and complexed CPT were 11.8
      x 10(-3) and 1.18 x 10(-3) min(-1), corresponding to an increase in half-life of
      CPT from 58.7 to 587.3 min, respectively. The preliminary cytotoxicity study
      against the human-derived myeloid THP-1 leukemia cell line showed RDM-beta-CD/CPT
      and HP-beta-CD/CPT complexes to be about two-fold more active than free CPT. In
      conclusion, the results showed that CDs, in general, and RDM-beta-CD, in
      particular, are effective complexing agents and can be used to improve the
      solubility and stability of CPT. The increase in cytotoxicity of CPT in the
      presence of CD is likely due to an increase in its stability.

PMID- 11849914
TI  - Pore formation in tablets compressed from binary mixtures as a result of
      deformation and relaxation of particles.
AB  - This paper describes the internal structure of tablets compressed from binary
      mixtures of sodium chloride and pregelatinised starch. The minimum particle
      diameter of pregelatinised starch inside tablets compressed from mixtures was
      calculated from the difference between the initial pore size distribution and the
      pore size distribution after removal of the starch particles by burning.
      Subsequently, the tablets were carefully crushed. These powders, consisting of
      almost only sodium chloride particles, were measured by laser diffraction. It was
      found that the diameter of the sodium chloride particles hardly changed, whereas
      the minimum diameter of starch particles strongly decreased during the compaction
      process. As an effect of the difference in yield pressure, the harder sodium
      chloride particles cause deformation of the softer starch particles, resulting in
      a change in particle shape. The pore size distribution of tablets compressed from
      mixtures of sodium chloride and starch is typically that of viscoelastic
      materials; the larger pores (>5 microm) change, while the small pores stay
      constant in number and size. The median pore diameter in tablets compressed from
      the mixtures is higher than the median pore diameter in tablets compressed from
      the pure materials. This paper shows that the formation of large pores was the
      result of the extra porosity expansion of tablets compressed from binary mixtures
      of sodium chloride and pregelatinised starch.

PMID- 11849915
TI  - Determination of piroxicam by solid-phase spectrophotometry in a continuous flow
      system.
AB  - A simple flow injection UV spectrophotometric method was developed for the
      determination of piroxicam. The method is based on its transient retention and
      concentration on Sephadex DEAE-A-25 anion-exchange gel beads packed in the flow
      cell and the continuous monitoring of its native absorbance on the solid phase at
      354 nm. The sample was injected into a 0.1 M NaCl carrier stream at pH 9.5 by
      using a simple monochannel FIA manifold. When the analytical signal reached a
      maximum value, piroxicam was eluted from the solid support by means of a
      desorbing solution (0.2 M, pH 4.5). The response of the sensor was linear in the
      concentration range 0.5-10 microg ml(-1) with a R.S.D. (%) of 1.8, a detection
      limit (3 sigma criterion) of 0.1 microg ml(-1) and a sampling rate of 13 h(-1).
      Application to the analysis of pharmaceutical samples testifies to the utility of
      this sensor. The accuracy of the proposed method was better than 5%.

PMID- 11849916
TI  - Determination of nelfinavir free drug concentrations in plasma by equilibrium
      dialysis and liquid chromatography/tandem mass spectrometry: important factors
      for method optimization.
AB  - A method was developed and validated for measuring the free fraction of
      nelfinavir in plasma employing equilibrium dialysis for the separation of free
      (unbound) drug and liquid chromatography/tandem mass spectrometry for
      quantitation. Nelfinavir, widely used to treat HIV infection, is a highly bound
      HIV protease inhibitor with the fraction bound in plasma being greater than 98%.
      Thus variations in the free fraction may be clinically important when
      interpreting total drug concentrations. Optimization of the method was carried
      out considering the influence of sample matrix and physicochemical and absorptive
      properties of nelfinavir. Nelfinavir free fraction averaged 0.41 +/- 0.094, 0.43
      +/- 0.087 and 0.41 +/- 0.063% at nelfinavir plasma concentrations of 1000, 2000
      and 3000 ng/ml, respectively. Free nelfinavir concentrations were underestimated
      with this assay by approximately 25% because of unavoidable losses to adsorption.
      However, the adsorptive loss was reproducible and consistent across the
      concentration range of the assay. Within-day and between-day precisions ranged
      from 6.0 to 9.4% and 15.2 to 27.3%, respectively. The lower limit of quantitation
      of the unbound concentration of nelfinavir was 1.0 ng/ml, permitting analysis of
      samples with total concentrations of nelfinavir in plasma that are > or = 400
      ng/ml. This developed method proves reproducible and sensitive and its
      application to patient plasma samples is also reported.

PMID- 11849917
TI  - In vitro phagocytosis and monocyte-macrophage activation with poly(lactide) and
      poly(lactide-co-glycolide) microspheres.
AB  - Treatment of many intracellular infections in the mononuclear phagocytic system
      (MPS), requires targeting of antibiotics by a drug delivery system. The objective
      of this study was to examine whether the particular nature of microspheres, made
      of end-group capped and uncapped poly(lactide) [PLA] and poly(lactide-co
      glycolide) [PLGA 50:50 and PLGA 75:25], affect the uptake into and also the
      activation of monocyte-macrophages. Placebo and gentamicin sulfate containing
      microspheres were incubated with J774 murine monocyte-macrophages and fresh human
      blood monocytes. Phagocytosis became more efficient with increasing polymer
      hydrophobicity, whereas opsonization of the particles in serum exerted
      inconsistent effects. Monocyte activation was determined by flow cytometry and
      measured as oxidative burst. The cellular oxidative burst induced by the
      particles was higher for end-group uncapped polymers. Opsonization increased
      significantly the oxidative activity of J774 monocytes, but affected
      inconsistently that of human blood monocytes. The results demonstrate that PLA
      and PLGA microspheres loaded with gentamicin sulfate were efficiently
      phagocytosed in vitro. The end-group uncapped polymer-type microspheres promoted
      significantly cell activation, which may be of importance for drug delivery and
      targeting to intracellular infections.

PMID- 11849918
TI  - Evaluation of the human serum albumin column as a discovery screening tool for
      plasma protein binding.
AB  - A total of 69 compounds with a variety of chemical structures were assayed using
      a human serum albumin column in combination with UV and mass spectrometric
      detection. A moderate correlation, R(2)=0.661, between the plasma protein
      binding, determined by traditional techniques of equilibrium dialysis or
      ultrafiltration, and chromatographic retention factor (k'/k'+1) was observed.
      Disparity between the regression line and numerous samples was observed across
      the entire range of plasma protein binding. Attempts to discriminate between
      compounds from the data set to achieve better correlation based physico-chemical
      properties were unsuccessful. Good agreement was observed for retention times
      obtained with UV detection with mobile phase containing phosphate buffer and mass
      spectrometric detection with mobile phase containing acetate buffer. Essentially
      identical data were obtained for compounds analyzed in singlet or cassette for
      minimally or highly bound (>90% bound) compounds. Analysis of cassettes
      containing compounds with plasma protein binding greater than 90% did not cause
      column overload, even at analyte concentrations up to 100 microg/ml. Diverse
      results were obtained when chromatographic retention was used to rank order
      various classes of compounds. Better correlation with ordering from known binding
      was obtained when a compound class contained a wide range of protein binding, in
      contrast to when compounds within a given class were all highly bound.

PMID- 11849919
TI  - Studies of the side chain cleavage of deramciclane in rats with radiolabelled
      compounds.
AB  - The pharmacokinetics of deramciclane and especially the fate of its side chain
      were studied in rats after oral treatment, using (3)H- and (14)C-labelled (ring-
      or side chain labelled) deramciclane and (14)C-dimethylamino-ethanol ((14)C-DMAE)
      radioisomers. The labelled compounds were admixed and the total radioactivities
      of both labels were simultaneously determined. The data obtained from the
      analysis of the plasma concentration-time curves revealed that an intensive
      cleavage (30-40%) of the side chain occurred at the ether bond. The core of
      deramciclane, carrying the ring label, was almost completely eliminated during 24
      h, while the elimination of the side chain was very slow (t(1/2)(beta): 99 h).
      The side chain residue most probably represents dimethylamino-ethanol, but the
      presence of dimethylglycine (DMG) cannot be excluded. The AUC(0-infinity) and the
      MRT values of DMAE were found to be much higher than those of the parent
      compound. In addition to the plasma levels, the time related changes of the
      tissue concentrations of the radioisomers of deramciclane were analysed both in
      the brain and the hypophysis. The concentration-time curves have shown similar
      characteristics to those of the plasma, but higher concentrations were reached in
      both organs (the highest in the hypophysis). It is postulated that the low rate
      of formation and elimination of the metabolite(s) (DMAE or DMG) indicates that,
      due to their endogenous nature, they can be incorporated into
      choline/acetylcholine or protein synthesis.

PMID- 11849920
TI  - The relative partitioning of neutral and ionised compounds in sodium dodecyl
      sulfate micelles measured by micellar electrokinetic capillary chromatography.
AB  - The rational use of micelles in quantitative structure-activity and quantitative
      structure-permeation relationships implies a good knowledge of the nature of
      recognition forces underlying solute-micelle association. The aims of this study
      were to unravel the intermolecular interaction forces responsible for the
      association of neutral and ionised compounds with negatively charged sodium
      dodecyl sulfate (SDS) micelles, using micellar electrokinetic capillary
      chromatography (MEKC). The MEKC capacity factors (log k(MEKC)) of 36 neutral
      model solutes were analysed by linear solvation free-energy relationships
      (LSERs). The results indicate that the size and H-bond acceptor strength of
      solutes are mainly responsible for their MEKC retention. Compared to n-octanol,
      the SDS micelles are more cohesive and stronger H-bond donors. Strong attractive
      electrostatic interactions govern solute-micelle association for positively
      charged compounds and micelles of the opposite charge, whereas repulsive
      electrostatic interactions occur between negatively charged solutes and micelles
      of the same charge. The capacity factors measured for the ionised forms of the
      acids and bases under study (log k(MEKC)(I)) indeed lie on two distinct plateau,
      about -1.0 for the former and about 2.0 for the latter and depend on the solute's
      charge more than on its chemical structure. Thus, the derivation of a diff(log
      k(MEKC)(N-I)) value, defined as the difference between the log k(MEKC) values of
      the neutral and charged species, strongly correlates with the respective log
      k(MEKC)(N) value and does not afford additional information.

PMID- 11849921
TI  - Multi-analyte capillary immunosensor for the determination of hormones in human
      serum samples.
AB  - In this work we present the development of a multi-analyte immunosensor for the
      determination of follitropin, human chorionic gonadotropin and prolactin in human
      serum. The immunosensor is based on plastic capillaries. According to the
      methodology, discrete areas of the internal capillary surface are coated with
      different antibodies, which are highly specific for each one of the analytes to
      be determined. The sample that will be analyzed along with a mixture of analyte
      specific biotinylated antibodies is introduced into the capillary. The coated and
      the detection antibodies react with different epitopes of the analytes in the
      sample to form a 'sandwich'. The detection is based on reaction of the
      immobilized biotinylated antibody with streptavidin labeled with R-phycoerythrin.
      The fluorescent areas formed were quantified by scanning the capillary with a
      light beam of appropriate wavelength. A light sensor placed at the end of the
      capillary detects the emitted photons, that are trapped and waveguided into the
      capillary walls. The multi-analyte immunosensor assays were characterized by high
      specificity and short analysis time. In addition, the results obtained by the
      multi-analyte optical capillary immunosensor were comparable to those obtained by
      immunofluorimetric assays performed in microtitration wells. Potential
      applications of the proposed immunosensor include determination of several
      analyte panels in a broad spectrum of disciplines such as endocrinology,
      hematology, and oncology.

PMID- 11849922
TI  - Biocompatible photolithographic process for the patterning of biomolecules.
AB  - A new approach for the patterning of biomolecule layers is introduced based on
      the design of a new photoresist material with biocompatible lithographic
      processing requirements. The photoresist is based on poly(t-butyl acrylate),
      which allows positive imaging with very dilute basic solutions, tolerable by
      selected biomolecules used in immunoanalysis. Sensitivity at lambda>300 nm is
      obtained using a suitable sulfonium salt photoacid generator. Thermal steps also
      take place under conditions tolerable by biomolecules. Lithographic results on Si
      wafer substrates show resolution capabilities for equal lines/spaces, down to the
      range of 5-10 microm under biocompatible conditions. The process is also used on
      substrates of different geometries, including inner capillary surfaces. The
      patterning of the inner surface of a polystyrene capillary with mouse IgG is
      reported to demonstrate the principles of the above approach.

PMID- 11849923
TI  - Electron beam patterning of biomolecules.
AB  - The patterning of biomolecules on semiconducting surfaces is of central
      importance in the fabrication of novel biodevices. In the process of patterning,
      it is required that the biomolecule preserves its properties and the substrate is
      not damaged by the chemicals, the temperatures or the patterning beams involved
      in the procedure. Recently, both DUV and electron beam microlithography have been
      used in order to deposit protein layers in predefined patterns. Various
      approaches have been used, some involving photoresists. Contrast between exposed
      and unexposed regions, resolution of adjacent features and sensitivity to dose
      variation, are the key issues. The approach followed in this paper consists of a
      direct patterning of a biotin layer, deposited on an amino-silane primed silicon
      nitride surface, using an electron beam. After irradiation, the surface is
      covered by bovine serum albumin (BSA), which acts as a blocking material to
      protect the exposed areas from streptavidin adsorption. Using 20 keV e-beam
      energy and doses, in the range 100-1000 microC/cm(2), submicrometer dense lines
      of 1-microm pitch have been obtained. The results have been tested by
      fluorescence optical microscopy.

PMID- 11849924
TI  - Gold-coated capillary based 2,4-dichlorophenoxyacetic acid chemi-luminescent
      assays: possibilities towards multianalysis.
AB  - The application of gold-coated glass capillaries for the design of a sensitive
      chemiluminescent immunoassay for 2,4-dichlorophenoxyacetic acid (2,4-D) is
      reported. The gold coating on the glass capillaries has been partially
      characterized and its effect on enhancing the signal intensity has been measured.
      A simple photo-multiplier tube-based photon detector is used for this purpose. At
      least three times improvement in the signal intensity is observed compared to
      uncoated glass capillaries, with a consequent improvement in the sensitivity of
      detection. Using such gold-coated glass capillaries, 2,4-D in the range 10(-9) to
      10(-13) mol/l is detectable at a precision of +/-15% (CV%) and a limit of
      detection of 10(-15) mol/l is achievable. The possibility of using such gold
      coated capillaries with a portable multianalytical set-up for field studies is
      also demonstrated.

PMID- 11849925
TI  - Optical multiple-analyte immunosensor for water pollution control.
AB  - A prototype of a portable optical immunosensor (called river analyser) has been
      developed. It can be applied for the monitoring of surface water quality.
      Antibodies carrying a fluorescent label are used for the specific recognition of
      pollutants, such as frequently applied pesticides. The transduction principle is
      based on total internal reflection fluorescence (TIRF). The outstanding advantage
      of the river analyser is, that at least three analytes can be detected
      simultaneously in one sample. Test cycles and fluid handling are automated and
      enable unattended measuring.

PMID- 11849926
TI  - Biosensor arrays for simultaneous measurement of glucose, lactate, glutamate, and
      glutamine.
AB  - For simultaneous measurement of glucose, lactate, glutamine, and glutamate a
      biosensor array is implemented in a micro flow-system thus giving a microsystem.
      The microsystem consists of a glass chip with the integrated biosensor array and
      a bottom part, which comprises a gold counter electrode, a 300 microm thick seal,
      and electrical interconnection lines. The flow device has a total internal volume
      of 2.1 or 6 microl when integrated with a mixer on chip. The biosensors with no
      crosstalking and high long term stability were produced by modifying the
      electrochemical transducers and utilizing photopatternable enzyme membranes. The
      use of appropriate miniaturization technology leads to mass producable devices
      for in vivo and ex vivo applications in whole blood and fermentation broth. Due
      to a novel glutaminase with an activity optimum in the neutral pH range direct
      and simultaneous monitoring of glutamine together with glucose, lactate, and
      glutamate could be performed.

PMID- 11849927
TI  - A generic strategy for subcloning antibody variable regions from the scFv phage
      display vector pCANTAB 5 E into pASK85 permits the economical production of F(ab)
      fragments and leads to improved recombinant immunoglobulin stability.
AB  - Apart from the decisive sensitivity and specificity of immunosensors, the
      employed antibodies essentially contribute to additional key factors like
      fabrication costs for sensor chips and sensor stability. A production scheme for
      recombinant antibody fragments has been optimised with respect to these
      particular issues of biosensor development. The phagemid vector pCANTAB 5 E is
      widely used for the selection of antibody fragments from corresponding libraries.
      However, large-scale production of the selected single-chain F(v) (scFv)
      fragments is substantially restricted by the high cost for the inducer IPTG and
      the anti-E-tag antibody. The latter is needed in significant amounts for the
      purification of the recombinant protein. A generic strategy was established for
      subcloning scFv variable regions from pCANTAB 5 E into the plasmid pASK85 for the
      expression of F(ab) fragments. pASK85 bears coding sequences for murine constant
      domains including a His(6) tag at the carboxyl-terminal end of the constant heavy
      chain domain. The anti-s-triazine antibody K47H served as a model system in this
      study. Biosynthesis of the F(ab) fragment in a high cell density fermenter was
      induced by addition of anhydrotetracycline. The F(ab) fragment was subsequently
      purified from the periplasmic extract in a single step by immobilized metal
      affinity chromatography (IMAC). A yield of 100 microg/lxOD(550) purified F(ab)
      fragment was obtained employing a standard fermentation scheme. The sensitivity
      and cross-reactivity of the F(ab) was comparable to the parent scFv when assayed
      by enzyme immunoassay. However, the F(ab) fragment exhibited significantly
      improved long-term stability.

PMID- 11849929
TI  - Sol-gel encapsulation of lactate dehydrogenase for optical sensing of L-lactate.
AB  - Sol-gel encapsulation of lactate dehydrogenase and its cofactor can be employed
      as a disposable sensor for L-lactate. The sensor utilized the changes in
      absorbance or fluorescence from the reduced cofactor nicotinamide adenine
      dinucleotide (NADH) upon exposure to L-lactate. Although, problems such as
      diminished enzymatic activity and/or leaching of enzyme from the sol-gel matrix
      occurred, the sol-gel process is sufficiently mild to permit retention of
      enzymatic activity. The apparent activity of LDH in the sensor is at least 10% of
      that of the dissolved enzyme. The sensor has a linear dynamic range over the
      normal physiological L-lactate level and has a long-term storage stability of at
      least 3 weeks.

PMID- 11849928
TI  - Design of novel electron transfer mediators based on indophenol derivatives for
      lactate sensor.
AB  - Novel indophenol derivatives which have limited solubility in water solution
      functioned as excellent electron-transfer mediators for lactate oxidase and a
      lactate sensor, showing good sensor performance, including a high sensitivity and
      good durability. These less water-soluble mediators were prepared by the O
      alkylation or acylation of indophenols in order to prevent the mediator being
      leached from the sensor. Consequently the characteristic substituent effects of
      indophenol derivatives were found to be follows, (1) modification of the phenolic
      OH group improved sensor durability; (2) the presence of chloride groups at the
      2,6-positions of the phenol ring improved the sensitivity of the sensor; (3) the
      introduction of substituents at the quinoide moiety led to a deterioration in
      durability. A mediator based lactate sensor using these derivatives was found to
      be nearly independent of oxygen concentration, showed a low level of interference
      effect, and a quite long durability.

PMID- 11849930
TI  - Biosensing of opioids using frog melanophores.
AB  - Spectacular color changes of fishes, frogs and other lower vertebrates are due to
      the motile activities of specialized pigment containing cells. Pigment cells are
      interesting for biosensing purposes since they provide an easily monitored
      physiological phenomenon. Melanophores, containing dark brown melanin pigment
      granules, constitute an important class of chromatophores. Their melanin-filled
      pigment granules may be stimulated to undergo rapid dispersion throughout the
      melanophores (cells appear dark), or aggregation to the center of the
      melanophores (cells appear light). This simple physiological response can easily
      be measured in a photometer. Selected G protein coupled receptors can be
      functionally expressed in cultured frog melanophores. Here, we demonstrate the
      use of recombinant frog melanophores as a biosensor for the detection of opioids.
      Melanophores were transfected with the human opioid receptor 3 and used for
      opiate detection. The response to the opioid receptor agonist morphine and a
      synthetic opioid peptide was analyzed by absorbance readings in an aggregation
      assay. It was shown that both agonists caused aggregation of pigment granules in
      the melanophores, and the cells appeared lighter. The pharmacology of the
      expressed receptors was very similar to its mammalian counterpart, as evidenced
      by competitive inhibition by increasing concentrations of the opioid receptor
      inhibitor naloxone. Transfection of melanophores with selected receptors enables
      the creation of numerous melanophore biosensors, which respond selectively to
      certain substances. The melanophore biosensor has potential use for measurement
      of substances in body fluids such as saliva, blood plasma and urine.

PMID- 11849931
TI  - In situ detection of calcium ions with chemically modified microcantilevers.
AB  - We report a novel technique of micromechanical detection of trace amounts of
      calcium ions by using microcantilevers modified with ion-selective self-assembled
      monolayers (SAMs). The SAM-modified microcantilevers undergo bending due to
      selective adsorption of calcium ions. Experiments conducted under flow conditions
      show that the modified cantilevers respond sensitively to calcium ions (Ca(2+));
      a Ca(2+) concentration of 10(-9) M can be detected with this technique. Other
      cations, such as Na(+) and K(+), do not have any effect on the deflection of
      these cantilevers. We demonstrate two different kinds of SAMs having selectivity
      for calcium ions.

PMID- 11849935
TI  - High-throughput screening for biocatalysts.
AB  - Recent progress in high-throughput enzyme assays includes new examples of
      fluorogenic and chromogenic substrates, fluorescence resonance energy transfer
      substrates, and applications of the pH and pM indicator methods. Recent
      developments of Horeau's pseudo-enantiomer derivatisation method to screen
      enantioselectivities in high-throughput have also been reported.

PMID- 11849936
TI  - Directed enzyme evolution.
AB  - Laboratory evolutionists continue to generate better enzymes for industrial and
      research applications. Exciting developments include new biocatalysts for
      enantioselective carbon-carbon bond formation and fatty acid production in
      plants. Creative contributions to the repertoire of evolutionary methods will
      ensure further growth in applications and expand the scope and complexity of
      biological design problems that can be addressed. Researchers are also starting
      to elucidate mechanisms of enzyme adaptation and natural evolution by testing
      evolutionary scenarios in the laboratory.

PMID- 11849937
TI  - Microbial epoxide hydrolases for preparative biotransformations.
AB  - Epoxide hydrolases from microbial sources are highly versatile biocatalysts for
      the asymmetric hydrolysis of epoxides on a preparative scale. Besides kinetic
      resolution, which furnishes the corresponding vicinal diol and remaining non
      hydrolysed epoxide in nonracemic form, enantioconvergent processes are possible:
      these are highly attractive as they lead to the formation of a single
      enantiomeric diol from a racemic oxirane. The data accumulated over recent years
      reveal a common picture of the substrate structure selectivity pattern of
      microbial epoxide hydrolases and indicate that substrates of various structural
      types can be selectively hydrolysed with enzymes from certain microbial sources.

PMID- 11849938
TI  - Hydantoinases and related enzymes as biocatalysts for the synthesis of unnatural
      chiral amino acids.
AB  - A cascade of hydantoinase, N-carbamoylase and hydantoinracemase can be used for
      the production of natural and unnatural chiral D- and L-amino acids from
      chemically synthesized hydantoin derivatives. Potentially, 100% conversion and
      100% optically pure amino acids can be obtained at the same time if racemic
      substrates are used. Recent research activities concentrate on newly isolated or
      improved enzymes and include directed evolution techniques, structure
      elucidation, studies of fusion proteins and the use of specially designed whole
      cell biocatalysts.

PMID- 11849939
TI  - Aromatic dioxygenases: molecular biocatalysis and applications.
AB  - Aromatic dioxygenases have been found to catalyse single and tandem oxidation
      reactions of conjugated polyenes. Rational selection and design of dioxygenases,
      allied to substrate shape, size and substitution pattern, has been used to
      control regiochemistry and stereochemistry during the oxygenation process. The
      resulting enantiopure bioproducts have been increasingly utilised as precursors
      for new and alternative routes in chiral synthesis.

PMID- 11849940
TI  - Biocatalytic synthesis of hydroxylated natural products using aldolases and
      related enzymes.
AB  - Synthetic building blocks bearing hydroxylated chiral centers are important
      targets for biocatalysis. Many C-C bond forming enzymes have recently been
      investigated for new applications and new strategies towards the synthesis of
      natural products and related oxygenated compounds. Several old catalysts have
      been studied to increase our functional knowledge of natural aldolase-type
      enzymes, and new mutated catalysts or catalytic antibodies have been tested for
      their synthetic utility.

PMID- 11849941
TI  - Biocatalytic synthesis of intermediates for the synthesis of chiral drug
      substances.
AB  - There has been an increasing awareness of the enormous potential of
      microorganisms and enzymes for the transformation of synthetic chemicals with
      high chemo-, regio- and enantioselectivity. Chiral intermediates and fine
      chemicals are in high demand, both from the pharmaceutical and agrochemical
      industries, for the preparation of bulk drug substances and agricultural
      products. Biocatalytic processes have been described for the synthesis of chiral
      intermediates for beta3- and beta2-receptor agonists, antihypertensive drugs,
      antiviral agents, melatonin receptor agonists, anticholesterol and anticancer
      drugs, and drugs to treat Alzheimer's disease.

PMID- 11849943
TI  - Advances in proteome analysis by mass spectrometry.
AB  - Proteome characterization using mass spectrometry is essential for the systematic
      investigation of biological systems and for the study of gene function. Recent
      advances in this multifaceted field have occurred in four general areas: protein
      and peptide separation methodologies; selective labeling chemistries for
      quantitative measurement of peptide and protein abundances; characterization of
      post-translational protein modifications; and instrumentation.

PMID- 11849944
TI  - The use of retroviruses as pharmaceutical tools for target discovery and
      validation in the field of functional genomics.
AB  - Retrovirally mediated functional genomics enables identification of
      physiologically relevant cellular therapeutic targets. Unique properties of
      retroviruses make them ideal tools for the introduction of large and diverse
      libraries of potential genetic effectors to a variety of cell types. The
      identification and recovery of intracellular library elements responsible for
      altered disease responses establishes a direct basis for pharmaceutical
      development. Recent innovations in retroviral infection efficiency and expression
      control have broadened application of the methodology to include libraries of
      mutagenized cDNAs, peptides and ribozyme genetic effectors.

PMID- 11849945
TI  - Functional genomics and target validation approaches using antisense
      oligonucleotide technology.
AB  - The recent increase in the amount and rate of accumulation of genomic information
      has created new challenges for the pharmaceutical industry. These include how
      best to rapidly and efficiently identify key genes responsible for complex
      disease phenotypes and how to use this information to develop new and specific
      classes of drugs. Antisense technology offers a powerful approach to identify
      novel cellular networks and signaling "cassettes" and provides a method to
      validate genes in vivo as attractive drug targets.

PMID- 11849946
TI  - In vivo drug target discovery: identifying the best targets from the genome.
AB  - A vast number of genes of unknown function threaten to clog drug discovery
      pipelines. To develop therapeutic products from novel genomic targets, it will be
      necessary to correlate biology with gene sequence information. Industrialized
      mouse reverse genetics is being used to determine gene function in the context of
      mammalian physiology and to identify the best targets for drug development.

PMID- 11849947
TI  - Custom DNA-binding proteins come of age: polydactyl zinc-finger proteins.
AB  - Artificial transcription factors based on modified zinc-finger DNA-binding
      domains have been shown to activate or repress the transcription of endogenous
      genes in multiple organisms. Advances in both the construction of novel zinc
      finger proteins and our understanding of the characteristics of a productive
      regulatory site have fueled these achievements.

PMID- 11849948
TI  - Synthetic cell biology.
AB  - Synthesis of data into formal models of cellular function is rapidly becoming a
      necessary industry. The complexity of the interactions among cellular
      constituents and the quantity of data about these interactions hinders the
      ability to predict how cells will respond to perturbation and how they can be
      engineered for industrial or medical purposes. Models provide a systematic
      framework to describe and analyze these complex systems. In the past few years,
      models have begun to have an impact on mainstream biology by creating deeper
      insight into the design rules of cellular signal processing, providing a basis
      for rational engineering of cells, and for resolving debates about the root
      causes of certain cellular behaviors. This review covers some of the recent work
      and challenges in developing these "synthetic cell" models and their growing
      practical applications.

PMID- 11849952
TI  - Measuring proteins on microarrays.
AB  - A prerequisite of proteomics is the ability to quantify many selected proteins
      simultaneously. Immunoassays on microarrays are an attractive solution, as
      equipment and antibodies are available and assays are simple, scalable and
      reproducible. Recently, considerable progress has been made in this area as
      evidenced by increased sensitivity and coverage (degree of multiplexing). Routine
      use of antibody microarrays in research and diagnostic settings will require
      increased availability of binding reagents, novel signal amplification
      procedures, inexpensive and robust platforms for microarray production and
      detection, and turn-key systems for running high-throughput assays.

PMID- 11849953
TI  - Metabolomics and microarrays for improved understanding of phenotypic
      characteristics controlled by both genomics and environmental constraints.
AB  - Advances in our understanding of functional genomics are best addressed by
      integrative studies that include measurements of mRNA, proteins, and low
      molecular weight metabolites over time and varied conditions. Bioinformatics can
      then be used to relate this data to the genome. Current technology allows for
      comprehensive and rapid mRNA expression profiling and mass spectrophotometric
      measurement of low molecular weight intermediates and metabolic products. In
      prokaryotic organisms, this combination provides a potentially powerful tool for
      identifying gene function and regulatory networks even in the absence of a
      combined proteomic approach.

PMID- 11849949
TI  - Biotechnology. Paper Alert.
AB  - A selection of interesting papers that were published in the two months before
      our press date in major journals most likely to report significant results in
      biotechnology.

PMID- 11849954
TI  - Stable carbon isotopes of lipid biomarkers: analysis of metabolites and metabolic
      fates of environmental microorganisms.
AB  - Lipid biomarkers are specific compounds that are characteristic of certain groups
      or species of microorganisms. The use of natural or labeled carbon isotopes of
      lipid biomarkers has enabled a better understanding of carbon flow pathways at
      the molecular level. Recent advances include, but are not limited to, the
      elucidation of mechanisms of anaerobic methane oxidation mediated by syntrophic
      sulfate-reducing bacteria and Archaea, linking microbial populations with
      specific microbial processes or bacterial transport mechanisms in natural or
      contaminated environments, and elucidation of the biosynthetic pathways of
      cellular material.

PMID- 11849955
TI  - Engineered allosteric ribozymes as biosensor components.
AB  - RNA and DNA molecules can be engineered to function as molecular switches that
      trigger catalytic events when a specific target molecule becomes bound. Recent
      studies on the underlying biochemical properties of these constructs indicate
      that a significant untapped potential exists for the practical application of
      allosteric nucleic acids. Engineered molecular switches can be used to report the
      presence of specific analytes in complex mixtures, making possible the creation
      of new types of biosensor devices and genetic control elements.

PMID- 11849956
TI  - Luminescent quantum dots for multiplexed biological detection and imaging.
AB  - Recent advances in nanomaterials have produced a new class of fluorescent labels
      by conjugating semiconductor quantum dots with biorecognition molecules. These
      nanometer-sized conjugates are water-soluble and biocompatible, and provide
      important advantages over organic dyes and lanthanide probes. In particular, the
      emission wavelength of quantum-dot nanocrystals can be continuously tuned by
      changing the particle size, and a single light source can be used for
      simultaneous excitation of all different-sized dots. High-quality dots are also
      highly stable against photobleaching and have narrow, symmetric emission spectra.
      These novel optical properties render quantum dots ideal fluorophores for
      ultrasensitive, multicolor, and multiplexing applications in molecular
      biotechnology and bioengineering.

PMID- 11849957
TI  - Biomolecular force measurements and the atomic force microscope.
AB  - The atomic force microscope (AFM) is a surface-sensitive instrument capable of
      imaging biological samples at nanometer resolution in all environments including
      liquids. The sensitivity of the AFM cantilever, to forces in the pico Newton
      range, has been exploited to measure breakaway forces between biomolecules and to
      measure folding-unfolding forces within single proteins. By attaching specific
      antibodies to cantilevers the simultaneous imaging of target antigens and
      identification of antigen-antibody interactions have been demonstrated.

PMID- 11849958
TI  - Protein transduction technology.
AB  - Intracellular delivery of macromolecules remains problematic because of the
      bioavailability restriction imposed by the cell membrane. Recent studies on
      protein transduction domains have circumvented this barrier, however, and have
      resulted in the delivery of peptides, full-length proteins, iron beads,
      liposomes, and radioactive isotopes into cells in culture and animal models in
      vivo.

PMID- 11849959
TI  - Ion/ion chemistry as a top-down approach for protein analysis.
AB  - Developing methodology for analyzing complex protein mixtures in a rapid fashion
      is one of the most challenging problems facing analytical biochemists today.
      Recent advances in mass spectrometry for the analysis of intact proteins (i.e.
      the top-down approach) show great promise for rapid protein identification. The
      ion/ion chemistry approach for the detection and identification of target
      proteins in complex matrices, determination of fragmentation channels as a
      function of precursor ion charge state, and post-translational modification
      characterization are discussed with particular emphasis on tandem mass
      spectrometry of intact proteins.

PMID- 11849960
TI  - Whole genome amplification--applications and advances.
AB  - The concept of whole genome amplification is something that has arisen in the
      past few years as the polymerase chain reaction (PCR) has been adapted to
      replicate regions of genomes that are of biological interest. The applications
      are many--forensic science, embryonic disease diagnosis, bioterrorism genome
      detection, "immortalization" of clinical samples, microbial diversity, and
      genotyping. Several recent papers suggest that whole genomes can be replicated
      without bias or non-random distribution of the target, these findings open up a
      new avenue to molecular biology.

PMID- 11849961
TI  - Biological data becomes computer literate: new advances in bioinformatics.
AB  - Bioinformatics is an art and science concerned with the use of computing in
      biological research areas such as genomics, transcriptomics, proteomics,
      genetics, and evolution. This review paints a broad picture of bioinformatics,
      drawing examples from genomic sequencing and microarray analysis. I highlight the
      role of bioinformatics at multiple points along the path from high-tech data
      generation to biological discovery.

PMID- 11849962
TI  - Predictive non-linear modeling of complex data by artificial neural networks.
AB  - An artificial neural network (ANN) is an artificial intelligence tool that
      identifies arbitrary nonlinear multiparametric discriminant functions directly
      from experimental data. The use of ANNs has gained increasing popularity for
      applications where a mechanistic description of the dependency between dependent
      and independent variables is either unknown or very complex. This machine
      learning technique can be roughly described as a universal algebraic function
      that will distinguish signal from noise directly from experimental data. The
      application of ANNs to complex relationships makes them highly attractive for the
      study of biological systems. Recent applications include the analysis of
      expression profiles and genomic and proteomic sequences.

PMID- 11849963
TI  - Argosomes: membrane fragments on the run.
AB  - Any biology student will know that the plasma membrane separates the inside of a
      cell from the outside world. Indeed, the plasma membrane is the guardian of a
      cell's physiology. Fewer students will be aware that cells can export bits of
      plasma membrane to distant sites in a tissue. Recent work demonstrates the
      transfer of membrane fragments in a live epithelium and, importantly, suggests
      that these fragments might be used as a vehicle to transport morphogens in a
      developing tissue.

PMID- 11849969
TI  - Insulin signaling pathways in time and space.
AB  - Despite remarkable progress in dissecting the signaling pathways that are crucial
      for the metabolic effects of insulin, the molecular basis for the specificity of
      its cellular actions is not fully understood. One clue might lie in the spatial
      and temporal aspects of signaling. Recent evidence suggests that signaling
      molecules and pathways are localized to discrete compartments in cells by
      specific protein interactions. Also, the rapid termination of tyrosine or lipid
      phosphorylation by phosphatases or serine kinases might tightly control the
      strength of a signaling pathway, thus determining its effect on growth,
      differentiation and metabolism.

PMID- 11849971
TI  - Flexible substrata for the detection of cellular traction forces.
AB  - By modulating adhesion signaling and cytoskeletal organization, mechanical forces
      play an important role in various cellular functions, from propelling cell
      migration to mediating communication between cells. Recent developments have
      resulted in several new approaches for the detection, analysis and visualization
      of mechanical forces generated by cultured cells. Combining these methods with
      other approaches, such as green-fluorescent protein (GFP) imaging and gene
      manipulation, proves to be particularly powerful for analyzing the interplay
      between extracellular physical forces and intracellular chemical events.

PMID- 11849970
TI  - Replication licensing--defining the proliferative state?
AB  - The proliferation of eukaryotic cells is a highly regulated process that depends
      on the precise duplication of chromosomal DNA in each cell cycle. Regulation of
      the replication licensing system, which promotes the assembly of complexes of
      proteins termed Mcm2-7 onto replication origins, is responsible for preventing re
      replication of DNA in a single cell cycle. Recent work has shown how the
      licensing system is directly controlled by cyclin-dependent kinases (CDKs).
      Repression of origin licensing is emerging as a ubiquitous route by which the
      proliferative capacity of cells is lowered, and Mcm2-Mcm7 proteins show promise
      as diagnostic markers of early cancer stages. These results have prompted us to
      propose a functional distinction between the proliferative state and the non
      proliferative state (including G0) depending on whether origins are licensed.

PMID- 11849972
TI  - Apoptotic DNA fragmentation and tissue homeostasis.
AB  - DNA fragmentation is a hallmark of apoptosis. The tightly controlled activation
      of the apoptosis-specific endonucleases provides an effective means to ensure the
      removal of unwanted DNA and the timely completion of apoptosis. Over the past
      several years, crucial progress has been made in identifying the long-awaited
      apoptotic endonucleases, and their importance in tissue homeostasis is beginning
      to unfold. Here, we focus on the most recent discoveries about the functions and
      mechanisms of these endonucleases in the context of apoptosis. We also discuss
      consequences that defective DNA fragmentation might have for tissue homeostasis
      and disease development.

PMID- 11849973
TI  - The yin and yang of the exosome.
AB  - Recent studies of the eukaryotic ribosomal RNA processing pathway have identified
      a complex of ten riboexonucleases called the exosome that plays a central role in
      the precise formation of the 3' ends of several types of RNAs. The exosome also
      destroys excess ribosomal RNA precursors and unused intermediates and degrades
      poly(A)-mRNAs in the cytoplasm. In the nucleus, the complex appears to function
      in a regulated mRNA surveillance system that degrades transcripts in response to
      defects in the mRNA processing and export pathways. How the cell regulates the
      nucleolytic prowess of the exosome to ensure correct and timely synthesis and
      destruction of RNAs is a central focus of current research.

PMID- 11849978
TI  - UV-induced changes in pigment content and light penetration in the fruticose
      lichen Cladonia arbuscula ssp. mitis.
AB  - The response of the lichen, Cladonia arbuscula (Wallr.) Flot. ssp. mitis
      (Sandst.) Ruoss to enhanced UV-B (280-315 nm) radiation was investigated with
      respect to: (a) changes in phenolic content; (b) differential pigment
      accumulation under visible and UV radiation with increasing distance from thallus
      apices; and (c) the internal distribution of UV-B radiation within the thallus
      measured with quartz optical fibres. In a short-term experiment, lichens were
      exposed for 7 days in a growth chamber to visible light with or without
      additional UV-B radiation. For a longer term experiment, lichens were grown
      outdoors under both natural UV radiation, and supplemental UV-A (315-400 nm)+UV-B
      provided by lamps. Controls were placed under filters that removed the radiation
      below 290 nm from the natural sunlight. The concentration of total phenolic
      compounds was measured spectrophotometrically at the termination of the
      experiments, in different parts of the lichen podetia. UV-exposed lichens showed
      increased accumulation of phenolics compared to those not grown under UV. At the
      termination of the long-term experiment, fibre optic measurements of the
      penetration of radiation into lichen thallus reflected the influence of growth
      under UV radiation, whereby UV was more strongly attenuated as compared to that
      in lichens not exposed to enhanced levels of UV-B radiation. Results indicated
      that in Cladonia, UV-B radiation induces the accumulation of phenolic compounds
      that may have a protective role. In addition, the morphological distribution of
      phenolic compounds was different under visible and supplemental UV-B radiation.
      Internal radiation measurements served to visualise the attenuation of radiation
      with thallus depth for different wavelengths in the UV-B waveband.

PMID- 11849977
TI  - The role of UV-B radiation in aquatic and terrestrial ecosystems--an experimental
      and functional analysis of the evolution of UV-absorbing compounds.
AB  - We analysed and compared the functioning of UV-B screening pigments in plants
      from marine, fresh water and terrestrial ecosystems, along the evolutionary line
      of cyanobacteria, unicellular algae, primitive multicellular algae, charophycean
      algae, lichens, mosses and higher plants, including amphibious macrophytes.
      Lichens were also included in the study. We were interested in the following key
      aspects: (a) does the water column function effectively as an 'external UV-B
      filter'?; (b) do aquatic plants need less 'internal UV-B screening' than
      terrestrial plants?; (c) what role does UV screening play in protecting the
      various plant groups from UV-B damage, such as the formation of thymine dimers?;
      and (d) since early land 'plants' (such as the predecessors of present-day
      cyanobacteria, lichens and mosses) experienced higher UV-B fluxes than higher
      plants, which evolved later, are primitive aquatic and land organisms
      (cyanobacteria, algae, lichens, mosses) better adapted to present-day levels of
      UV-B than higher plants? Furthermore, polychromatic action spectra for the
      induction of UV screening pigments of aquatic organisms have been determined.
      This is relevant for translating 'physical' radiation measurements of solar UV-B
      into 'biological' and 'ecological' effects. From the action spectra, radiation
      amplification factors (RAFs) have been calculated. These action spectra allow us
      to determine any mitigating or antagonistic effects in the ecosystems and
      therefore qualify the damage prediction for the ecosystems under study. We
      summarize and discuss the main results based on three years of research of four
      European research groups. The central theme of the work was the investigation of
      the effectiveness of the various screening compounds from the different species
      studied in order to gain some perspective of the evolutionary adaptations from
      lower to higher plant forms. The induction of mycosporine-like amino acids (MAAs)
      was studied in the marine dinoflagellate Gyrodinium dorsum, the green algal
      species Prasiola stipitata and in the cyanobacterium Anabaena sp. While visible
      (400-700 nm) and long wavelength UV-A (315-400 nm) showed only a slight effect,
      MAAs were effectively induced by UV-B (280-315 nm). The growth of the lower land
      organisms studied, i.e. the lichens Cladina portentosa, Cladina foliacaea and
      Cladonia arbuscula, and the club moss Lycopodiumannotinum, was not significantly
      reduced when grown under elevated UV-B radiation (simulating 15% ozone
      depletion). The growth in length of the moss Tortula ruralis was reduced under
      elevated UV-B. Of the aquatic plants investigated the charophytes Chara aspera
      showed decreased longitudinal growth under elevated UV-B. In the 'aquatic higher
      plants' studied, Ceratophyllum demersum, Batrachium trichophyllum and Potamogeton
      alpinus, there was no such depressed growth with enhanced UV-B. In Chara aspera,
      neither MAAs nor flavonoids could be detected. Of the terrestrial higher plants
      studied, Fagopyrum esculentum, Deschampsia antarctica, Vicia faba, Calamagrostis
      epigejos and Carex arenaria, the growth of the first species was depressed with
      enhanced UV-B, in the second species length growth was decreased, but the shoot
      number was increased, and in the latter two species of a dune grassland there was
      no reduced growth with enhanced UV-B. In the dune grassland species studied
      outdoors, at least five different flavonoids appeared in shoot tissue. Some of
      the flavonoids in the monocot species, which were identified and quantified with
      HPLC, included orientin, luteolin, tricin and apigenin. A greenhouse study with
      Vicia faba showed that two flavonoids (aglycones) respond particularly to
      enhanced UV-B. Of these, quercetin is UV-B inducible and mainly located in
      epidermal cells, while kaempferol occurs constitutively. In addition to its UV
      screening function, quercetin may also act as an antioxidant. Polychromatic
      action spectra were determined for induction of the UV-absorbing pigments in
      three photosynthetic organisms, representing very different taxonomic groups and
      different habitats. In ultraviolet photobiology, action spectra mainly serve two
      purposes: (1) identification of the molecular species involved in light
      absorption; and (2) calculation of radiation amplification factors for assessing
      the effect of ozone depletion. Radiation amplification factors (RAFs) were
      calculated from the action spectra. In a somewhat simplified way, RAF can be
      defined as the percent increase of radiation damage for a 1% depletion of the
      ozone layer. Central European summer conditions were used in the calculations,
      but it has been shown that RAF values are not critically dependent on latitude or
      season. If only the ultraviolet spectral region is considered, the RAF values
      obtained are 0.7 for the green alga Prasiola stipitata, 0.4 for the
      dinoflagellate Gyrodinium dorsum, and 1.0 for the cyanobacterium Anabaena sp. In
      the case of P. stipitata, however, the effect of visible light (PAR,
      photosynthetically active radiation, 400-700 nm) is sufficient to lower the RAF
      to about 0.4, while the PAR effect for G. dorsum is negligible. RAFs for some
      damage processes, such as for DNA damage (RAF=2.1 if protective effects or
      photorepair are not considered [1]), are higher than those above. Our
      interpretation of this is that if the ozone layer is depleted, increased damaging
      radiation could overrule increased synthesis of protective pigments. In addition
      to investigating the functional effectiveness of the different screening
      compounds, direct UV effects on a number of key processes were also studied in
      order to gain further insight into the ability of the organisms to withstand
      enhanced UV-B radiation. To this end, the temperature-dependent repair of
      cyclobutane dimers (CPD) and (6-4) photoproducts induced by enhanced UV-B was
      studied in Nicotiana tabacum, and the UV-B induction of CPD was studied in the
      lichen Cladonia arbuscula. Also, photosynthesis and motility were monitored and
      the response related to the potential function of the screening compounds of the
      specific organism.

PMID- 11849979
TI  - Flavonoid concentrations in three grass species and a sedge grown in the field
      and under controlled environment conditions in response to enhanced UV-B
      radiation.
AB  - An investigation was carried out to find whether enhanced levels of UV-B
      radiation induce increased concentrations of flavonoids in the leaves of the
      grass species Deschampsia antarctica, Deschampsia borealis and Calamagrostis
      epigeios and the sedge Carex arenaria. Whether the enhanced levels of UV-B
      influenced the proportions of the various flavonoids in the leaves was also
      studied. Increased flavonoid concentrations would improve the UV-B shielding of
      UV-B susceptible tissues. Using HPLC analysis the flavonoids orientin and
      luteolin were identified in D. antarctica, orientin in D. borealis and tricin in
      C. arenaria. Neither flavonoid concentrations nor the proportion of the various
      flavonoids in climate room grown D. antarctica and D. borealis plants differed
      between individuals grown under 0, ambient or elevated UV-B levels. After 12
      weeks of growth biomass production and shoot-to-root ratios of D. antarctica were
      not affected by elevated UV-B radiation. Greenhouse grown C. epigeios plants
      contained higher concentrations and different proportions of flavonoids grown
      under elevated levels of UV-B than when grown under ambient or 0 UV-B. In C.
      epigeios plants grown in their natural habitat in the field under ambient or
      elevated levels of UV-B, flavonoid concentrations and proportions were the same
      in plants from both treatments. In the leaves of the sedge C. arenaria grown in a
      greenhouse flavonoid concentrations and proportions were not affected by UV-B
      radiation. Leaves were harvested four times during the growing season from C.
      arenaria plants grown in their natural habitat in the field under ambient or
      elevated levels of UV-B. Leaves harvested in January contained higher
      concentrations of flavonoids when grown under elevated UV-B than when grown under
      ambient UV-B radiation. In leaves harvested in May, September and December
      flavonoid concentrations were the same in plants grown under ambient or elevated
      UV-B. The proportion of the different flavonoids was the same for both treatments
      in all months. These results indicate that constitutive levels of flavonoids in
      these grass and sedge species are adequately high to protect them against ambient
      and elevated levels of solar UV-B radiation.

PMID- 11849980
TI  - Growth and production of buckwheat (Fagopyrum esculentum) treated with reduced,
      ambient, and enhanced UV-B radiation.
AB  - The effect of enhanced UV-B radiation on buckwheat (Fagopyrum esculentum Moench.
      variety 'Darja'), an important high elevation crop, was studied in order to
      estimate its vulnerability in changing UV-B environment. Plants were grown in
      outdoor experiments from July to October under reduced and ambient UV-B levels,
      and an UV-B level simulating 17% ozone depletion in Ljubljana. During the
      development the following parameters were monitored: light saturated
      photosynthetic activity, transpiration, potential and effective photochemical
      efficiencies of photosystem II, the contents of photosynthetic pigments and
      methanol soluble UV-B absorbing compounds. At the end of the experiment, growth
      rate and production of seeds were estimated. In the following growth season the
      seeds collected from plants exposed to different UV-B treatments were tested for
      germination capacity. Total UV-B absorbing compounds during plant development
      were increased by UV-B radiation, photosynthetic pigments (chlorophyll a and b
      and carotenoids) decreased. Photosynthetic rate was lowered in an early stage of
      development. UV-B treatment resulted in the increase in the transpiration rate
      and consequently the decrease in water use efficiency (WUE). The disturbances in
      water economy and in photosynthesis affected the reproduction potential
      negatively; the production of seeds in plants cultivated under ambient and
      enhanced UV-B was 57 and 39% of the production of specimens treated with reduced
      UV-B, respectively. The germination of seeds collected from treated plants
      revealed on average about 95% success, independently of the treatment, but the
      time needed for germination was the shortest for seeds developed under enhanced
      UV-B level treatment. Enhanced UV-B radiation affected water relations and
      production of buckwheat, but not the potential of seeds for germination.

PMID- 11849981
TI  - The influence of enhanced UV-B radiation on Batrachium trichophyllum and
      Potamogeton alpinus -- aquatic macrophytes with amphibious character.
AB  - The responses of two amphibious species, Batrachium trichophyllum and Potamogeton
      alpinus to different UV-B environments were studied. Plant material from natural
      environments, as well as from outdoor treatments was examined. In long-term
      outdoor experiments plants were grown under three different levels of UV-B
      radiation: reduced and ambient UV-B levels, and a UV-B level simulating 17% ozone
      depletion. The following parameters were monitored: contents of total methanol
      soluble UV-absorbing compounds and chlorophyll a, terminal electron transport
      system (ETS) activity and optimal and effective quantum yield of photosystem II.
      No effect of the different UV-B levels on the measured parameters was observed.
      The amount of UV-B absorbing compounds seems to be saturated, since no
      differences were observed between treatments and no increase was found in peak
      season, when natural UV-B levels were the highest. Physiological measurements
      revealed no harmful effects; neither on potential and actual photochemical
      efficiency, nor on terminal ETS activity. The contents of UV-B absorbing
      compounds were examined also in plant material sampled in low and high altitude
      environments during the growth season. Both species exhibited no seasonal
      dynamics of production of UV-absorbing compounds. The contents were variable and
      showed no significant differences between high and low altitude populations.

PMID- 11849982
TI  - Polychromatic action spectrum for the induction of a mycosporine-like amino acid
      in a rice-field cyanobacterium, Anabaena sp.
AB  - A polychromatic action spectrum for the induction of an ultraviolet
      absorbing/screening mycosporine-like amino acid (MAA) has been determined in a
      filamentous and heterocystous nitrogen-fixing rice-field cyanobacterium, Anabaena
      sp. High-performance liquid chromatographic (HPLC) studies revealed the presence
      of only one type of MAA, which was identified as shinorine, a bisubstituted MAA
      containing both glycine and serine groups having a retention time at 2.8 min and
      an absorption maximum at 334 nm. Exposure of cultures to simulated solar
      radiation in combination with various cut-off filters (WG 280, 295, 305, 320,
      335, 345, GG 400, 420, 455, 475, OG 515, 530, 570, RG 645, 665 and a broad-band
      filter, UG 11) clearly revealed that the induction of the MAA takes place only in
      the UV range. Photosynthetic active radiation (PAR) had no significant impact on
      MAA induction. The ratio of the absorption at 334 nm (shinorine) to 665 nm
      (chlorophyll a) and the action spectrum also showed the induction of MAA to be UV
      dependent peaking in the UV-B range at around 290 nm. The results indicate that
      the studied cyanobacterium, Anabaena sp. may protect itself from deleterious
      short wavelength solar radiation by its ability to synthesize a mycosporine-like
      amino acid in response to UV-B radiation and thereby screen the negative effects
      of UV-B.

PMID- 11849983
TI  - Induction of the synthesis of an UV-absorbing substance in the green alga
      Prasiola stipitata.
AB  - The chlorophyte Prasiola stipitata produces a UV-absorbing substance with an
      absorption maximum at 324 nm. The wavelength-dependent induction of the synthesis
      of this substance was investigated using simulated solar radiation in combination
      with 15 cut-off and one broad-band filter. The algae were exposed from three
      different distances (89, 100 and 119 cm) to the solar simulator producing a
      maximum of 203.58, 1.24 and 46.86 W/m(2) and a minimum of 107.94, 0.64 and 24.44
      W/m(2) irradiances for PAR, UV-B and UV-A, respectively. A polychromatic action
      spectrum was calculated from the pooled results showing a clear maximum at 300 nm
      in the long-wavelength UV-B range, but there is still some induction caused by UV
      A and PAR. The ratio of the effectiveness from PAR to UV-A to UV-B amounts to
      1:2:22.

PMID- 11849984
TI  - Wavelength dependence of mycosporine-like amino acid synthesis in Gyrodinium
      dorsum.
AB  - The synthesis or accumulation of mycosporine-like amino acids (MAAs) is an
      important UV tolerance mechanism in aquatic organisms. To investigate the
      wavelength dependence of MAA synthesis in the marine dinoflagellate Gyrodinium
      dorsum, the organism was exposed to polychromatic radiation (PAR and UV) from a
      solar simulator for up to 72 h. Different irradiance spectra were produced by
      inserting various cut-off filters between lamp and samples. A polychromatic
      action spectrum for the synthesis of MAA synthesis was constructed. PAR and long
      wavelength UV-A radiation showed almost no effect while the most effective
      wavelength range was around 310 nm. Shorter wavelengths where less effective in
      the induction of MAA synthesis. Wavelengths below 300 nm damaged the organisms
      severely as indicated by a decrease in chlorophyll a absorption.

PMID- 11849985
TI  - Temperature-dependent formation and photorepair of DNA damage induced by UV-B
      radiation in suspension-cultured tobacco cells.
AB  - Two photoproducts of DNA damage, i.e. cyclobutane pyrimidine dimers (CPDs) and 6
      4 photoproducts (6-4PPs), induced by UV-B radiation in suspension-cultured
      tobacco cells were quantified by enzyme-linked immunosorbent assay (ELISA) with
      monoclonal antibodies. CPDs and 6-4PPs were induced in tobacco cells by UV-B
      radiation. Photorepair of CPDs was faster than that of 6-4PPs. UV-B radiation
      induces formation of CPDs and 6-4PPs even at 0 degrees C, but low temperature
      significantly decreases the UV-B-induced (in contrast to UV-C-induced) formation
      of CPDs and 6-4PPs. Low temperature also retarded the removal of CPDs and 6-4PPs
      under white light, and almost no photorepair of CPDs and 6-4PPs was detected at 0
      degrees C. When purified DNA from tobacco cells grown in darkness was irradiated
      with UV-B, formation of CPDs and 6-4PPs took place at the same speed at different
      temperatures. It indicated that formation of CPDs and 6-4PPs induced by UV-B was
      temperature-independent in a non-cellular system. Based on our results for
      suspension-cultured tobacco cells, not only the photorepair but also UV-B-induced
      formation of CPDs and 6-4PPs are temperature-dependent.

PMID- 11849986
TI  - Involvement of reactive oxygen species in the UV-B damage to the cyanobacterium
      Anabaena sp.
AB  - Reactive oxygen species (ROS) are involved the damage of living organisms under
      environmental stress including UV radiation. Cyanobacteria, photoautotrophic
      prokaryotic organisms, also suffer from increasing UV-B due to the depletion of
      the stratospheric ozone layer. The increased UV-B induces the production of ROS
      in vivo detected by using the ROS-sensitive probe 2',7'
      dichlorodihydrofluorescein diacetate (DCFH-DA). Ascorbic acid and N-acetyl-L
      cysteine (NAC) scavenged ROS effectively, while alpha-tocopherol acetate or
      pyrrolidine dithiocarbamate (PDTC) did not. The presence of rose bengal and
      hypocrellin A increased the ROS level by photodynamic action in the visible
      light. The presence of the herbicide, 3-(3,4-dichlorophenyl)-1,1-dimethyl urea
      (DCMU), increased ROS production slightly, and ROS formation was greatly enhanced
      by the addition of methyl viologen due to the fact that this redox system diverts
      electrons from PSI to oxygen and thus forms ROS. UV-B induces ROS generation by
      photodynamic action and inhibition of the electron transport by damaging the
      electron receptors or enzymes associated with the electron transport chain during
      photosynthesis.

PMID- 11849987
TI  - The European Light Dosimeter Network: four years of measurements.
AB  - The European Light Dosimeter Network (ELDONET) has now been functional for more
      than four years. The network is based on dosimeters which measure radiation in
      three biologically relevant wavelength bands (UV-B, 280-315 nm; UV-A, 315-400 nm;
      and Photosynthetic Active Radiation, PAR, 400-700 nm). The ELDONET network is
      currently based on 33 stations with 40 instruments. The distribution of the
      instruments all over Europe allows measurement of the latitudinal and
      longitudinal light climate distribution. In addition, several instruments are
      active in South America, New Zealand, India, Africa and Japan. With some
      exceptions, the measured yearly doses depend on the latitude. While the maximal
      daily doses are almost comparable from station to station, seasonal changes and
      the different maximal solar zenith angles account for the differences in total
      yearly doses. Ratioing between UV-B and PAR allows the detection of subtle
      changes in the local light climate, due, for example, to mini-ozone holes
      encountered in northern Europe during spring. Comparison of satellite ozone data
      with terrestrial ELDONET measurements revealed an overall weak correlation
      between these data sets. However, local weather conditions, solar zenith angle
      and latitude as well as reflectivity (i.e. clouds and aerosol; satellite data)
      show a much stronger correlation to the doses received. The close relationship
      between the spectral sensitivity of the UV-B sensor used in the ELDONET dosimeter
      and the CIE erythemal action spectrum allows determination of the erythemal dose
      on the basis of the dosimeter readings.

PMID- 11849988
TI  - Myelin proteolipid protein--the first 50 years.
AB  - Myelin proteolipid protein (PLP), the most abundant protein of central nervous
      system (CNS) myelin, is a hydrophobic integral membrane protein. Because of its
      physical properties, which make it difficult to work with, progress towards
      determining the exact function(s) and disease associations of myelin PLP has been
      slow. However, recent molecular biology advances have given new life to
      investigations of PLP, and suggest that it has multiple functions within myelin
      and is of importance in several neurological disorders.

PMID- 11849989
TI  - Bilirubin: its role in cytoprotection against oxidative stress.
AB  - Bilirubin, the end product of heme catabolism in mammals, is generally regarded
      as a potentially cytotoxic, lipid-soluble waste product that needs to be
      excreted. However, in the last 10 years, in vitro and in vivo studies, have
      demonstrated that bilirubin exhibits potent anti-oxidant properties preventing
      the oxidative damage triggered by a wide range of oxidant-related stimuli.
      Therefore, the idea of a beneficial and physiological role for bilirubin in
      cytoprotection against short and long-lasting oxidant-mediated cell injury is
      highlighted here.

PMID- 11849990
TI  - Hypericin in cancer treatment: more light on the way.
AB  - Photodynamic therapy (PDT) has been described as a promising new modality for the
      treatment of cancer. PDT involves the combination of a photosensitizing agent
      (photosensitizer), which is preferentially taken up and retained by tumor cells,
      and visible light of a wavelength matching the absorption spectrum of the drug.
      Each of these factors is harmless by itself, but when combined they ultimately
      produce, in the presence of oxygen, cytotoxic products that cause irreversible
      cellular damage and tumor destruction. Hypericin, a powerful naturally occurring
      photosensitizer, is found in Hypericum perforatum plants, commonly known as St.
      John's wort. In recent years increased interest in hypericin as a potential
      clinical anticancer agent has arisen since several studies established its
      powerful in vivo and in vitro antineoplastic activity upon irradiation.
      Investigations of the molecular mechanisms underlying hypericin photocytotoxicity
      in cancer cells have revealed that this photosensitizer can induce both apoptosis
      and necrosis in a concentration and light dose-dependent fashion. Moreover, PDT
      with hypericin results in the activation of multiple pathways that can either
      promote or counteract the cell death program. This review focuses on the more
      recent advances in the use of hypericin as a photodynamic agent and discusses the
      current knowledge on the signaling pathways underlying its photocytotoxic action.

PMID- 11849992
TI  - Dog liver glucose-6-phosphate dehydrogenase: purification and kinetic properties.
AB  - Glucose-6-phosphate dehydrogenase (G6PD) catalyses the first step of the pentose
      phosphate pathway which generates NADPH for anabolic pathways and protection
      systems in liver. G6PD was purified from dog liver with a specific activity of
      130 U x mg(-1) and a yield of 18%. PAGE showed two bands on protein staining;
      only the slower moving band had G6PD activity. The observation of one band on
      SDS/PAGE with M(r) of 52.5 kDa suggested the faster moving band on native protein
      staining was the monomeric form of the enzyme. Dog liver G6PD had a pH optimum of
      7.8. The activation energy, activation enthalpy, and Q10, for the enzymatic
      reaction were calculated to be 8.96, 8.34 kcal x mol(-1), and 1.62,
      respectively.The enzyme obeyed "Rapid Equilibrium Random Bi Bi" kinetic model
      with Km values of 122 +/- 18 microM for glucose-6-phosphate (G6P) and 10 +/- 1
      microM for NADP. G6P and 2-deoxyglucose-6-phosphate were used with catalytic
      efficiencies (kcat/Km) of 1.86 x 10(6) and 5.55 x 10(6) M(-1) x s(-1),
      respectively. The intrinsic Km value for 2-deoxyglucose-6-phosphate was 24 +/-
      4mM. Deamino-NADP (d-NADP) could replace NADP as coenzyme. With G6P as
      cosubstrate, Km d-ANADP was 23 +/- 3mM; Km for G6P remained the same as with NADP
      as coenzyme (122 +/- 18 microM). The catalytic efficiencies of NADP and d-ANADP
      (G6P as substrate) were 2.28 x 10(7) and 6.76 x 10(6) M(-1) x s(-1),
      respectively. Dog liver G6PD was inhibited competitively by NADPH (K(i)=12.0 +/-
      7.0 microM). Low K(i) indicates tight enzyme:NADPH binding and the importance of
      NADPH in the regulation of the pentose phosphate pathway.

PMID- 11849991
TI  - Altered liver gene expression in CCl4-cirrhotic rats is partially normalized by
      insulin-like growth factor-I.
AB  - We have previously shown that the administration of low doses of insulin-like
      growth factor-I (IGF-I) to CCl4-cirrhotic rats improves liver function and
      reduces fibrosis. To better understand the mechanisms behind the hepatoprotective
      effects of IGF-I, and to identify those genes whose expression is affected in
      cirrhosis and after IGF-1 treatment, we have performed differential display of
      mRNA analysis by means of polymerase chain reaction (PCR) in livers from control
      and CCl4-cirrhotic rats treated or not with IGF-I. We have identified 16 genes
      that were up- or down-regulated in the cirrhotic liver. IGF-I treatment partially
      normalized the expression of eight of these genes, including serine proteinase
      inhibitors such as serpin-2 and alpha-1-antichymotripsin, alpha-1-acid
      glycoprotein, and alpha-2u-globulin. Additionally, we show that IGF-I enhanced
      the regenerative activity in the cirrhotic liver, as determined by the increased
      expression of the proliferating cell nuclear antigen (PCNA). Finally, IGF-I
      treatment partially restored the expression of growth hormone receptor (GHR) and
      the levels of global genomic DNA methylation, which are reduced in human and
      experimental cirrhosis. Taken together, our observations confirm the
      hepatoprotective effects of IGF-I, and suggest that this action can be exerted in
      part through the normalization of liver gene expression, growth hormone (GH)
      responsiveness and global genomic DNA methylation.

PMID- 11849993
TI  - In vitro interaction of eukaryotic elongation factor 2 with synthetic
      oligoribonucleotide that mimics GTPase domain of rat 28S ribosomal RNA.
AB  - Eukaryotic elongation factor 2 (eEF2) catalyzed the translocation of peptidyl
      tRNA from the ribosomal A site to the P site. In this paper, the interaction
      between eEF2 and GTD RNA, a synthetic oligoribonucleotide that mimicked the
      GTPase domain of rat 28S ribosomal RNA, was studied in vitro. The purified eEF2
      could bind to GTD RNA, forming a stable complex. Transfer RNA competed with GTD
      RNA in binding to eEF2, whereas poly(A), poly(U) and poly(I, C) did not interfere
      with the interaction between eEF2 and GTD RNA, demonstrating that the tertiary
      structure of RNA might be necessary for the recognition of and binding to eEF2.
      The complex formation of eEF2 with GTD RNA was inhibited by SRD RNA, a synthetic
      oligoribonucleotide mimic of Sarcin/Ricin domain RNA of rat 28S RNA. Similarly,
      GTD RNA inhibited the interaction between eEF2 and SRD RNA. This fact implies
      that these small oligoribonucleotides probably share similar recognition or
      binding identity elements in their tertiary structures. In addition, the binding
      of eEF2 to GTD RNA could be obviously weakened by the ADP-ribosylation of eEF2
      with diphtheria toxin. These results indicate that eEF2 behaves differently from
      prokaryotic EF-G in binding to ribosomal RNA.

PMID- 11849994
TI  - Dipyridamole prevents the coconut oil-induced hypercholesterolemia. A study on
      lipid plasma and lipoprotein composition.
AB  - For a better understanding of the hypolipidemic function of dipyridamole, we have
      studied the comparative effects of diet supplementation with 10% coconut oil with
      and without dipyridamole on the lipid plasma and lipoprotein composition in
      chicks. This study was performed under postprandial and food-deprivation (12h)
      conditions. Coconut oil induced a clear hypercholesterolemia under both feeding
      conditions. Simultaneous administration of dipyridamole maintained total and
      esterified cholesterol at levels similar to those observed in control animals
      sacrificed under postprandial conditions. Under these conditions, our results
      also show that dipyridamole significantly reduced cholesterol levels in all the
      chick plasma lipoproteins that were increased by coconut oil administration.
      Nevertheless, it should be emphasised that the levels of total cholesterol found
      in intermediate- and very-low-density lipoproteins were lower than in control.
      All chemical components of these fractions were significantly decreased by
      dipyridamole. The effects were not significant in chicks deprived of food. In
      conclusion, our results show that the hypercholesterolemia induced by coconut oil
      was prevented by dipyridamole. To our knowledge, this is one of the first reports
      on the antihypercholesterolemic effects of dipyridamole.

PMID- 11849995
TI  - Hyperthermic stress stimulates the association of both constitutive and inducible
      isoforms of 70 kDa heat shock protein with rat liver glucocorticoid receptor.
AB  - Glucocorticoid hormone receptor exists in the cytoplasm of target cells in the
      form of dynamic multiprotein heterocomplexes with heat shock proteins Hsp90 and
      Hsp70, and additional components of the molecular chaperone machinery. Whole body
      hyperthermic stress was previously shown to induce alterations in protein
      composition of these complexes increasing the share of Hsp70, but participation
      of individual Hsp70 family members was not investigated. In the present study the
      association of glucocorticoid receptor with constitutive and inducible forms of
      Hsp70 in the liver cytosol of rats exposed to 41 degrees C whole body
      hyperthermic stress was examined. Immunoprecipitation of glucocorticoid receptor
      heterocomplexes by monoclonal anti-receptor antibody (BuGR2) followed by
      quantitative immunoblotting revealed the presence of both nucleocytoplasmic Hsp70
      family members, constitutive--Hsc70 and inducible--Hsp72, within the complexes.
      Immediately after the stress only Hsc70 was found in association with
      glucocorticoid receptor. However, after the induction of Hsp72 by stress, its
      appearance within the glucocorticoid receptor heterocomplexes was also recorded
      and the presence of both Hsp70 forms within the heterocomplexes was evident by
      the end of examined 24h period after the stress. This study confirms that heat
      stress affects protein composition of rat liver glucocorticoid receptor
      heterocomplexes increasing the share of Hsp70 and shows that this increase could
      be equally ascribed to constitutive and inducible forms of Hsp70.

PMID- 11849997
TI  - A graphic representation of protein sequence and predicting the subcellular
      locations of prokaryotic proteins.
AB  - Zp curve, a three-dimensional space curve representation of protein primary
      sequence based on the hydrophobicity and charged properties of amino acid
      residues along the primary sequence is suggested. Relying on the Zp parameters
      extracted from the three components of the Zp curve and the Bayes discriminant
      algorithm, the subcellular locations of prokaryotic proteins were predicted.
      Consequently, an accuracy of 81.5% in the cross-validation test has been achieved
      using 13 parameters extracted from the curve for the database of 997 prokaryotic
      proteins. The result is slightly better than that of using the neural network
      method (80.9%) based on the amino acid composition for the same database. By
      jointing the amino acid composition and the Zp parameters, the overall predictive
      accuracy 89.6% can be achieved. It is about 3% higher than that of the Bayes
      discriminant algorithm based merely on the amino acid composition for the same
      database. The prediction is also performed with a larger dataset derived from the
      version 39 SWISS-PROT databank and two datasets with different sequence
      similarity. Even for the dataset of non-sequence similarity, the improvement can
      be of 4.4% in the cross-validation test. The results indicate that the Zp
      parameters are effective in representing the information within a protein primary
      sequence. The method of extracting information from the primary structure may be
      useful for other areas of protein studies.

PMID- 11849996
TI  - Ribosomal scanning on the highly structured insulin-like growth factor II-leader
      1.
AB  - The complex architecture of human insulin-like growth factor (IGF) II-leader 1 of
      592 nucleotides (nt), with one open reading frame (ORF), and the potential to
      fold into stable structures makes efficient linear ribosomal scanning difficult
      to comprehend. Indeed, leader 1-driven reporter expression is low in rabbit
      reticulocyte lysate. Contrarily, leader 1 is very efficient in cells. Therefore,
      we tested whether this 5'UTR uses an alternative mechanism for translation
      initiation in vivo, internal entry or ribosomal shunting. Internal initiation was
      tested by introducing leader 1 into the intercistronic region of a bicistronic
      vector. Second cistron expression, driven by leader 1, was lower than by the
      intercistronic beta-globin 5'UTR, indicating that leader 1 does not contain an
      internal ribosomal entry site (IRES). Shunting was tested by inserting hairpin
      (HP) structures, capable of blocking ribosomal scanning, at eight positions in
      leader 1. After transfection, these mutant 5'UTRs were incapable of directing
      reporter expression. Less stable HPs at the same positions increased the activity
      to 50% of wild-type activity, indicating that insertions at these positions are
      not disastrous for initiation. These data indicate that the translational
      machinery encounters major parts of leader 1. As scanning seems unlikely, and
      internal entry and shunting were shown not to occur, we discuss a modified
      scanning mechanism for architecturally complex 5'UTRs.

PMID- 11849998
TI  - Blurring the distinctions between insect pests of animals and plants.
AB  - The Royal Entomological Society International Symposium on Insects and Disease
      was held at the University of Aberdeen on 10-12 September 2001. The symposium was
      run alongside the society's Annual Meeting (the first time this meeting has been
      held outside England) in association with the International Union of Forest
      Research Organisations and the Entomological Society of The Netherlands. The
      symposium was divided into three sessions: The Insect-Host-Disease Interface;
      Ecology, Epidemiology and Modelling, and Insect Control in the New Millennium.

PMID- 11849999
TI  - So what if parasites vary?
AB  - The British Society for Parasitology Autumn Symposium was held on 14 September
      2001 at the Linnean Society of London, UK, only a few yards from the room in
      which Darwin and Wallace presented their joint papers on organic variation.
      Fittingly, the symposium--Parasite variation: immunological and ecological
      significance--considered the consequences of parasite variation.

PMID- 11850000
TI  - Neospora 2001.
AB  - Infection with the protozoan parasite Neospora caninum is emerging as a major
      cause of reproductive loss in cattle worldwide. Recent advances in research with
      the ultimate goal of devising effective and sustainable control measures were
      discussed at Neospora 2001. Neospora 2001 was held, 13-15 September 2001, at the
      Moredun Research Institute, Edinburgh, UK. The international meeting covered many
      aspects of bovine neosporosis including diagnosis, epidemiology and immunology.

PMID- 11850004
TI  - The implications of naturally acquired immunity to malaria in Southeast Asia.

PMID- 11850005
TI  - Human helminth infections--future research foci.

PMID- 11850007
TI  - Pigment biocrystallization in Plasmodium falciparum.

PMID- 11850008
TI  - The cost of not treating bednets.
AB  - For centuries, bednets have been used as a physical barrier against biting
      insects. Recent epidemiological investigations into their protective effects
      against malaria were quickly overtaken by studies focusing on the benefits of
      impregnating bednets with insecticide. The operational problems encountered in re
      treating bednets with insecticide are often cited as an impediment to wide-scale
      implementation. The evidence for a protective effect of untreated nets against
      malaria is presented here alongside an analysis of how well untreated nets would
      need to work in order to compete with treated nets within a cost-effectiveness
      framework.

PMID- 11850009
TI  - Trypanosome hydrolases and the blood-brain barrier.
AB  - African trypanosomes cross the blood-brain barrier, but how they do so remains an
      area of speculation. We propose that proteases, such as the trypanopains and
      oligopeptidases that are released by trypanosomes, could mediate in this process.
      The trypanosomes also possess cell-surface-associated acid phosphatases that
      could play a role in invasion similar to that in advancing cancer cells. Such
      enzymes, perhaps acting in concert, have the potential to cause tissue
      degradation and ease the passage of the trypanosomes through various tissues in
      the host, including the blood-brain barrier.

PMID- 11850010
TI  - Anisakis simplex: dangerous--dead and alive?
AB  - The risk of infection with Anisakis simplex and related parasites of fish has
      been recognized for some time, but it is now emerging that ingestion of material
      from dead parasites in food is also potentially dangerous. The resulting allergic
      reactions range from rapid onset and potentially lethal anaphylactic reactions to
      chronic, debilitating conditions. This review discusses the problems and clinical
      implications associated with A. simplex, other related conditions, and the way in
      which disease manifestations vary from person to person.

PMID- 11850011
TI  - Resistance and susceptibility in human onchocerciasis--beyond Th1 vs. Th2.
AB  - As research progress has led to programs for the elimination of onchocerciasis as
      a public health problem, research must now be intensified to protect elimination
      efforts. A profound understanding of the immunology in the human-parasite
      relationship is required for predicting the impacts of an altered immune response
      in a population post-microfilaricide treatment, and for the development of a
      vaccine against onchocerciasis, a highly desirable tool to guarantee sustained
      elimination success. This article summarizes the recent advancements in
      understanding the human immune mechanisms against onchocerciasis, and focuses on
      the new concept of T-cell suppressor responses as a major counterbalance
      mechanism for effector responses driven by T helper 1 and T helper 2 cells
      against the filarial worms.

PMID- 11850012
TI  - Plasmodium sex determination and transmission to mosquitoes.
AB  - In order to be transmitted by their mosquito vector, malaria parasites undergo
      sexual reproduction, which occurs between specialized male and female parasites
      (gametes) within the blood meal in the mosquito. Nothing was known about how
      Plasmodium determines the sex of its gametocytes (gamete precursors), which are
      produced in the vertebrate host. Recently, erythropoietin, the vertebrate hormone
      controlling erythropoiesis in response to anaemia, was implicated in Plasmodium
      sex determination in animal models of malaria. This review examines the available
      information and addresses the relevance of such a sex determining mechanism for
      Plasmodium falciparum transmission to mosquitoes, with special reference to low
      gametocytaemias.

PMID- 11850013
TI  - DNA microarrays for malaria.
AB  - DNA microarrays are a powerful tool for the analysis of RNA and DNA composition
      on a whole-genome scale. The first applications of this technology in
      parasitology are in place. This review examines the various approaches to
      Plasmodium transcript-profiling that are being adopted using DNA microarray
      analysis and discusses additional strategies for obtaining and collating
      information relevant to the search for drug and vaccine candidates in malaria.

PMID- 11850019
TI  - Apoptosis and successful aging.

PMID- 11850020
TI  - Between Scylla and Charybdis: p53 links tumor suppression and aging.

PMID- 11850021
TI  - Murine leukemia virus in organs of senescence-prone and -resistant mouse strains.
AB  - A series of inbred strains of mice have been developed that are either prone
      (SAMP) or resistant (SAMR) to accelerated senescence. All of these strains
      originated from an inadvertent cross or crosses between the AKR/J mouse strain
      and an unknown strain(s). The characteristics of the nine senescence-prone lines
      differ, with all strains showing generalized aspects of accelerated aging but
      with each line having a specific aging-related change that is emphasized, e.g.
      learning and memory deficits, osteoporosis and senile amyloidosis. The senescence
      resistant strains have normal patterns of aging and do not show the specific
      aging-related changes seen in SAMP strains. The fact that AKR mice have high
      levels of endogenous, ecotropic murine leukemia virus (MuLV) prompted an
      examination of the expression levels of MuLV in SAM strains. Analysis of brain,
      spleen and thymus samples revealed that seven of nine SAMP strains had high
      levels of MuLV and contained the Emv11 provirus (previously termed Akv1) that
      encodes the predominant MuLV found in AKR mice. In contrast, none of the SAMR
      strains had Emv11 or significant amounts of virus. The current findings represent
      an initial step in determining the role of MuLV in the accelerated senescence
      seen in SAMP strains.

PMID- 11850022
TI  - The telomeric length and heterogeneity decrease with age in normal human oral
      keratinocytes.
AB  - We have examined the telomere length in NHOK explanted from 28 donors between the
      ages of 21 and 84 years. Genomic DNA was isolated from exponentially replicating
      NHOK and digested with HinFI to yield terminal restriction fragments (TRF). The
      TRF length ranged from 4.1 to 7.0 kbp with a mean of 5.3 +/- 0.8 kbp, which was
      significantly shorter than that (8.9 +/- 1.0 kbp) of normal human oral
      fibroblasts (NHOF). The TRF length was inversely correlated to the increase of
      donor age in NHOK (m=-23 bp per year; r=-0.60; P<0.001). Also, the heterogeneity
      of TRF length in cultured NHOK decreased with increased donor age (r=-0.38,
      P<0.05). These data indicated that clonogenic NHOK cells had replicated in situ
      and showed a progressive shortening of TRF length. The short telomere length and
      decreased telomeric length heterogeneity in immortalized cells suggested that
      there is a critical minimum for cell survival.

PMID- 11850023
TI  - Age differentially influences estrogen receptor-alpha (ERalpha) and estrogen
      receptor-beta (ERbeta) gene expression in specific regions of the rat brain.
AB  - Estradiol's ability to influence neurochemical events that are critical to female
      reproductive cyclicity and behavior decreases with age. We tested the hypothesis
      that decreases in estrogen receptor-alpha (ERalpha) and/or ERbeta mRNA explain
      the brain's declining responsiveness to estradiol. We assessed ERalpha and ERbeta
      mRNA levels in intact and ovariectomized estradiol-treated rats. ERbeta mRNA was
      detected in several brain regions and decreased by middle-age in the cerebral
      cortex and supraoptic nucleus of estradiol-treated rats. ERbeta mRNA levels
      exhibited a diurnal rhythm in the suprachiasmatic nucleus of young and middle
      aged rats and this rhythm was blunted in old rats. We examined ERalpha mRNA in
      the periventricular preoptic, medial preoptic, ventromedial and arcuate nuclei,
      and it was decreased only in the periventricular preoptic nucleus of the old
      rats. In summary, the expression of ERalpha and ERbeta mRNAs is differentially
      modulated in the aging brain and changes are region specific.

PMID- 11850025
TI  - Enhanced apoptosis in prolonged cultures of senescent porcine pulmonary artery
      endothelial cells.
AB  - Senescent or aged endothelial cells in culture remain metabolically active after
      cessation of division, and are generally believed to eventually die. However,
      mechanisms underlying the terminal aging of cultured cells, i.e. from senescence
      to death, are poorly understood. Here, we report that culturing of replicative
      senescent endothelial cells for a prolonged period of time without passaging
      leads to enhanced programmed cell death or apoptosis. Senescent (passage 45) and
      young (passage 3) porcine pulmonary artery endothelial cells (PAEC) were cultured
      for 0-42 days post confluence. The cells attached to culture dishes and floating
      in medium were collected at 0, 7, 14, 21, 28, 35 and 42 days post confluence and
      were assessed for markers of apoptosis. Morphology studies showed that ratios
      between senescent and young cells attached to dishes declined to 45% after 42
      days postconfluence. Apoptotic cells in prolonged cultures of senescent PAEC
      increased from 5 to 35% as determined by protein mass, DNA breakage, and caspase
      3 activation. Steady state levels of Bcl-2, an anti-apoptotic protein, in
      senescent prolonged cultures decreased to less than 20% for all time points
      compared with young cells. Relative levels of Bad, a pro-apoptotic protein, in
      senescent cells were elevated from 60 to 130% during prolonged culturing. These
      results indicate that terminal cellular aging enhances apoptosis and the levels
      of Bcl-2/Bad may be associated with the apoptotic process in porcine lung
      endothelial cells.

PMID- 11850024
TI  - Effects of aging on hepatic IGF-I signaling.
AB  - Little is known regarding hepatic insulin-like growth factor-1 IGF-I signaling
      with aging despite the observation that other tissues demonstrate resistance to
      IGF-I with aging and declines in liver mass accompany aging. Our aim was to
      determine if the IGF-I-induced signaling process changes with aging. Young (5
      months) and old (24 months) C57BL/6 mice hepatic tissues and blood samples were
      taken 20 min after an intraperitoneal injection of desIGF-I. Age had no
      significant effect on plasma glucose, insulin and total IGF-I levels. IRS-1
      protein was significantly decreased (33%) with aging. Basal phosphorylation of
      IRS-1, PKB and ERK were unaffected whereas basal phosphorylation of CREB and FKHR
      were significantly increased (37 and 33%, respectively) with aging. desIGF-I
      caused a significant decrease in plasma glucose concentrations in both young
      (53%) and old (44%) mice. desIGF-I administration significantly increased the
      phosphorylation of IRS-1 in both young (104%) and old (89%) hepatic tissues.
      Similarly, the phosphorylation of PKB was dramatically enhanced in both young
      (527%) and old (350%) hepatic tissues after desIGF-I stimulation. By contrast,
      desIGF-I administration had no significant effects on the phosphorylation of ERK
      and phosphorylation of transcription factors CREB and FKHR in both young and old
      hepatic tissues. These data suggest that aging dose not impair IGF-I signaling in
      hepatic tissues.

PMID- 11850026
TI  - Growth hormone influences the content and composition of collagen in the aorta
      from old rats.
AB  - Collagen and elastin are major components of the aortic extracellular matrix and
      crucial in determining the stiffness of the aorta. We recently showed that growth
      hormone (GH) changes the mechanical properties, content and composition of aortic
      collagen from young rats. In the present study, the effect of GH on aorta from
      old rats was investigated. Old female rats (18(1/2)-20(1/2) months) were injected
      with either GH (5 mg/kg per day; n=15) or vehicle (n=14) for 80 days. Mechanical
      and biochemical properties of the thoracic aorta were investigated. Long-term GH
      injections increased the body weight of female rats by 47% accompanied by a
      threefold increase in serum IGF-I. The diameter of the aorta was increased by 5%,
      resulting in a 10% increase in the cross-section of the aortic lumen. Growth
      hormone increased the content of collagen per sample by 6% and increased the
      amount of type I collagen relative to type III collagen. No changes in the
      mechanical properties or elastin content per sample were found. In conclusion, GH
      induced a substantial growth of old rats. However, although the diameter and the
      collagen content were increased, the mechanical properties of the aorta were
      preserved in the GH-injected rats.

PMID- 11850027
TI  - New age patterns of survival improvement in Sweden: do they characterize changes
      in individual aging?
AB  - The parameters of the Gompertz approximation to the mortality curve are
      negatively correlated. Strehler and Mildvan [Science 132 (1960) 14] predicted
      this property of the mortality curve using a mathematical model of mortality and
      aging and then confirmed it in empirical studies. Despite the fact that their
      theory was based on the cohort model of mortality the SM correlation was also
      revealed in the analysis of period mortality data. In fact, most applications of
      the SM model to human data use Gompertz's approximation to the period mortality
      rate. Many researchers studying SM correlation consider it a universal
      demographic law. Such correlation prescribes a certain regularity in mortality
      changes. All mortality curves must intersect at one point. Mortality decline must
      produce the rectangularization of survival curves. In this paper we investigated
      the changes in the patterns of mortality decline in Sweden between 1861 and 1999.
      We found a difference in patterns of SM correlation for cohort and period
      mortality data. We investigated trends in survival improvement and found that the
      tendency to rectangularization of the survival curve existed for only a limited
      period of time. Then it was gradually replaced by near parallel shift of the
      survival curve to the right. We found that the pattern of SM correlation was
      relatively stable only at certain phases of the survival history of male and
      female populations. We analyzed past and recent patterns of survival changes and
      discussed possible causes for instability of SM correlation both in cohort and in
      period mortality data.

PMID- 11850028
TI  - Activation of an adipogenic program in adult myoblasts with age.
AB  - Myoblasts isolated from mouse hindlimb skeletal muscle demonstrated increased
      adipogenic potential as a function of age. Whereas myoblasts from 8-month-old
      adult mice did not significantly accumulate terminal markers of adipogenesis
      regardless of culture conditions, myoblasts from 23-month-old mice accumulated
      fat and expressed genes characteristic of differentiated adipocytes, such as the
      fatty acid binding protein aP2. This change in differentiation potential was
      associated with a change in the abundance of the mRNA encoding the transcription
      factor C/EBPalpha, and in the relative abundance of PPARgamma2 to PPARgamma1
      mRNAs. Furthermore, PPARgamma activity appeared to be regulated at the level of
      phosphorylation, being more highly phosphorylated in myoblasts isolated from
      younger animals. Although adipogenic gene expression in myoblasts from aged
      animals was activated, presumably in response to PPARgamma and C/EBPalpha,
      unexpectedly, myogenic gene expression was not effectively repressed. The Wnt
      signaling pathway may also alter differentiation potential in muscle with age.
      Wnt-10b mRNA was more abundantly expressed in muscle tissue and cultured
      myoblasts from adult compared with aged mice, resulting in stabilization of
      cytosolic beta-catenin, that may potentially contribute to inhibition of
      adipogenic gene expression in adult myoblasts. The changes reported here,
      together with those reported in bone marrow stroma with age, suggest that a
      default program may be activated in mesenchymal cells with increasing age
      resulting in a more adipogenic-like phenotype. Whether this change in
      differentiation potential contributes to the increased adiposity in muscle with
      age remains to be determined.

PMID- 11850029
TI  - Enhancement of lipopolysaccharide-stimulated cyclooxygenase-2 mRNA expression and
      prostaglandin E2 production in gingival fibroblasts from individuals with Down
      syndrome.
AB  - It is well known that Down syndrome (DS) is a premature ageing syndrome.
      Periodontal disease in individuals with DS develops rapidly and extensively in a
      relatively younger age bracket compared with that in healthy controls. The
      mechanisms involved in the periodontal inflammatory processes in DS patients are
      not fully understood. In the present study, the non-inflamed gingival fibroblasts
      isolated from seven patients with DS (DGF) and seven healthy controls (NDGF) were
      stimulated with lipopolysaccharide (LPS) derived from Actinobacillus
      actinomycetemcomitans (A. a.). We measured the level of prostaglandin E2 (PGE2)
      production by DGF and NDGF by radioimmunoassay, and also measured the mRNA
      expression of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) by using the
      real-time PCR method. We found the higher levels of LPS-stimulated COX-2 mRNA
      expression and PGE2 production in DGF when compared with those in NDGF. This
      study may indicate that overexpression of LPS-stimulated COX-2 induced a greater
      ability of DGF to produce PGE2, and that these phenomena may be responsible for
      the severer periodontal disease in DS patients.

PMID- 11850030
TI  - Metallothioneins (I+II) and thyroid-thymus axis efficiency in old mice: role of
      corticosterone and zinc supply.
AB  - Thymic atrophy or thymus absence causes depressed thyroid-thymus axis (TTA)
      efficiency in old, young propyl-thiouracil (PTU) (experimental hypothyroidism)
      and in young-adult thymectomised (Tx) mice, respectively. Altered zinc turnover
      may be also involved in depressed TTA efficiency. Zinc turnover is under the
      control of zinc-bound metallothioneins (Zn-MTs) synthesis. Thyroid hormones,
      corticosterone and nutritional zinc affect Zn-MT induction. Zn-MT releases zinc
      in young-adult age during transient oxidative stress for prompt immune response.
      In constant oxidative stress (ageing and liver regeneration after partial
      hepatectomy), high liver Zn-MTs, low zinc ion bioavailability and depressed TTA
      efficiency appear. This last finding suggested that MT might not release zinc
      during constant oxidative stress leading to impaired TTA efficiency. The aim of
      this work/study is to clarify the role of Zn-MTs (I+II) in TTA efficiency during
      development and ageing. The main results are (1) Old and PTU mice display high
      corticosterone, enhanced liver MTmRNA, low zinc and depressed TTA efficiency
      restored by zinc supply. Increased survival and no significant increments in
      basal liver Zn-MTs proteins occur in old and PTU mice after zinc supply. (2) Lot
      of zinc ions bound with MT in the liver from old mice than young (HPLC). (3)
      Young-adult Tx mice, evaluated at 15 days from thymectomy, display high MTmRNA
      and nutritional-endocrine-immune damage restored by zinc supply or by thymus
      grafts from old zinc-treated mice. (4) Young-adult Tx mice, but evaluated at 40
      days from thymectomy, display natural normalisation in MTmRNA and nutritional
      endocrine-immune profile with survival similar to normal mice. (5) Stressed
      (constant dark for 10 days) mice overexpressing MT display low zinc, depressed
      immunity, reduced thymic cortex, high corticosterone, altered thyroid hormones
      turnover showing a likeness with old mice. These findings, taken altogether, show
      that corticosterone is pivotal in MTs induction under stress. MTs bind
      preferentially zinc ions in constant oxidative stress, but with no release of
      zinc from MT leading to impaired TTA efficiency. Zinc supply restores the defect
      because zinc has no interference in affecting pre-existing Zn-MTs protein
      concentrations in old and PTU mice. Therefore, free zinc ions are available for
      TTA efficiency after zinc supply. Thymus from old zinc-treated mice induces the
      same restoring effect when transplanted in Tx recipients. However, Tx mice
      display natural normalisation in MTmRNA and in nutritional-endocrine-immune
      profile in the long run. Therefore, Zn-MTs (I+II) are crucial in zinc homeostasis
      for endocrine-immune efficiency during the entire life assuming a role of
      potential and novel 'biological clock of ageing'.

PMID- 11850031
TI  - Ageing is associated with a decrease in the number of sarcolemmal ATP-sensitive
      K+ channels in a gender-dependent manner.
AB  - The opening of sarcolemmal K(ATP) channels is considered to be an important
      endogenous cardioprotective mechanism. On the other hand, age-dependent changes
      in the myocardial susceptibility to ischemia and hypoxia have been observed in
      different species, including humans. Here, we have hypothesized that aging might
      be associated with the changes in sarcolemmal K(ATP) channels. Therefore, the
      main objective of the present study was to establish whether aging changes
      expression of cardiac sarcolemmal ATP-sensitive K+ (K(ATP)) channels. RT-PCR
      using primers specific for K(ATP) channel subunits, Kir6.2, Kir6.1 and SUR2A
      subunits was performed using total RNA from guinea-pig ventricular tissue. Whole
      cell electrophysiology was done on isolated guinea-pig ventricular
      cardiomyocytes. Western blotting using anti-Kir6.2 and anti-SUR2A antibodies was
      performed on cardiac membrane fraction. Tissue and cells were harvested from
      young and old, male and female guinea-pigs. RT-PCR analysis did not reveal
      significant age-related changes in levels of Kir6.1 or Kir6.2 mRNAs. However,
      levels of SUR2A were significantly lower in old than in young females. Such age
      differences were not observed with cardiac tissue from male animals. In both old
      and young males, pinacidil (100 microM) induced outward currents. The difference
      between current density of pinacidil-sensitive component in females, but not
      males, was statistically significant. Western blotting analysis revealed higher
      levels of Kir6.2 and SUR2A proteins in cardiac membrane fraction from young than
      old females. The present study demonstrates that in females, but not males, aging
      is associated with decrease in number of cardiac K(ATP) channels which is due to
      decrease in levels of the SUR2A subunit.

PMID- 11850033
TI  - Schwann cell-enriched cultures from adult human peripheral nerve: a technique
      combining short enzymatic dissociation and treatment with cytosine arabinoside
      (Ara-C).
AB  - Attempts to design the nerve cellular prostheses have focused on the production
      of autologous Schwann cells expanded in vitro as the essential component in the
      regeneration process of injured peripheral nerves. To obtain human Schwann cells
      of high quality we tested a short enzymatic dissociation protocol that optimized
      cellular viability levels. We also assessed patterns of bromodeoxyuridine (BrdU)
      incorporation in both Schwann cells and fibroblasts in the presence or absence of
      the antimitotic Ara-C, an enrichment option for adult human Schwann cell
      cultures. The Ara-C treated cultures showed a significantly higher Schwann cell
      percentage (95%), compared with that obtained in the absence of Ara-C (70%),
      indicating that this antimitotic acts to eliminate fibroblasts in each one of the
      applied pulses (four pulses). However, we have observed that the use of this
      antimitotic during prolonged periods of time produced a cumulative effect causing
      Schwann cell cytotoxicity. Therefore, we consider that our enzymatic dissociation
      technique and the application of only two pulses of Ara-C to the cultures are
      enough to achieve enrichment of adult human Schwann cells in culture.

PMID- 11850032
TI  - The inhibition of calcium signaling in T lymphocytes from old mice results from
      enhanced activation of the mitochondrial permeability transition pore.
AB  - Aging attenuates calcium signaling in T lymphocytes from old mice. Aging also
      attenuates the sustained elevation of cell free calcium by ionomycin, which is
      similar to the T cell receptor signal. In T lymphocytes from young mice, the
      ionomycin-induced elevation of cell free calcium was inhibited by collapsing the
      mitochondrial membrane potential by uncouplers and ionophores, and activation of
      the permeability transition. In T lymphocytes from old mice, the mitochondrial
      membrane potential was largely collapsed, but cyclosporin and N-methyl-val-4
      cyclosporin, inhibitors of the permeability transition, restored the
      mitochondrial potential, as well as the ionomycin-induced elevation of cell free
      calcium. In addition, the generation of reactive oxygen species in the presence
      of mitochondrial electron transport inhibitors was relatively enhanced in T
      lymphocytes from old mice. The association between low rhodamine 123 fluorescence
      and attenuated calcium signaling in T lymphocytes from old mice is also shown to
      be a consequence of the collapsed mitochondrial potential. These results suggest
      that Ca2+ signaling is attenuated in T lymphocytes from old mice because of an
      enhanced activation of the permeability transition.

PMID- 11850034
TI  - Visualization of individual axons in excised lamprey spinal cord by magnetic
      resonance microscopy.
AB  - The direct visualization of axons within their native tissue environment by
      magnetic resonance (MR) microscopy is presented for the first time in the excised
      larval sea lamprey spinal cord. A home-built transverse radio frequency coil of
      1.5 mm diameter was used in conjunction with a commercial 400 MHz MR microscopy
      system, implementing both 2-D and 3-D imaging pulse sequences. Images having
      nominal voxel sizes of 9x9x500 and 9x9x125 microm(3), respectively, in the
      lamprey spinal cord were obtained, resolving individual Mauthner and Muller
      axons. Furthermore, architectural changes associated with axonal degeneration
      were visualized in the spinal cord of one animal, excised 8 weeks after
      hemisection of the cord. Although the lamprey previously has not been the subject
      of MR microscopy investigations, these results demonstrate the method's potential
      for imaging this axon system, which is an important model of spinal cord injury
      and regeneration.

PMID- 11850036
TI  - Discrimination of brain's neuroelectric responses by a decision-making function.
AB  - The aim of this work was to develop a mathematical decision-making procedure that
      might become a basis for real-time pattern recognition studies of the brain's
      neuroelectric responses. Data were collected from 77 volunteers under the
      auditory oddball paradigm with standard (1000 Hz) and deviant (2000 Hz) stimuli.
      The participants counted the deviants and reported them at the end of the
      experimental session. Event-related potentials (ERPs) were recorded and filtered
      with a bandpass between 0.16 and 70 Hz (3 dB down, 12 dB/octave) at Fz- and Pz
      recording sites. The most significant potential values that discriminated the
      responses to the deviant stimuli group were at 136, 224, 328, 348, and 350 ms for
      Fz, and at 166, 220, and 350 ms for the Pz. The 328, 348, and 350 ms potential
      values define the curvature of the P300 peak; the 224 ms potential at Fz, and the
      220 ms at Pz define that of the N2b peak. The differentiation between the deviant
      and standard group was checked through a discriminant function that allowed
      prediction of group membership; 98% of the ERP responses were correctly
      identified. The results showed that statistically derived time-points were
      congruent with the P300 and N2b ERP curvature.

PMID- 11850035
TI  - Spatio-temporal patterns of neuronal activity: analysis of optical imaging data
      using geometric shape matching.
AB  - Optical imaging of neuronal network activity yields information of spatial
      dynamics which generally is analyzed visually. The transient appearance of
      spatial activity patterns is difficult to gauge in a quantifiable manner, or may
      even altogether escape detection. Here, we employ geometric shape matching using
      Frechet distances or straight skeletons to search for pre-selected patterns in
      optical imaging data with adjustable degrees of tolerance. Data were sampled from
      fluorescence changes of a voltage-sensitive dye recorded with a 464-photodiode
      array. Fluorescence was monitored in a neuronal network in vitro. Neuronal
      activity prompting fluorescence fluctuations consisted of spontaneous
      epileptiform discharges in neocortical slices from patients undergoing epilepsy
      surgery. The experiments show that: (a) spatial activity patterns can be detected
      in optical imaging data; (b) shapes such as "mini-foci" appear in close
      correlation to bioelectric discharges monitored with field potential electrodes
      in a reproducible manner; (c) Frechet distances yield more conservative matches
      regarding rectangular, and less conservative hits with respect to radially
      symmetric shapes than the straight skeleton approach; and (d) tolerances of 0.03
      0.1 are suited to detect faithful images of pre-selected shapes, whereas values
      >0.8 will report matches with any polygonal pattern. In conclusion, the methods
      reported here are suited to detect and analyze spatial, geometric dynamics in
      optical imaging data.

PMID- 11850037
TI  - Multiple response measures during classical conditioning.
AB  - Animal research assessing multiple responses during Pavlovian conditioning has
      revealed a dichotomy between the central nervous system (CNS) substrates for
      somatomotor and visceral CRs. These findings have implications for the study of
      clinical/applied problems in human subjects, since differences in the acquisition
      functions for these response systems may suggest which CNS structures are
      involved in various neuropsychiatric disorders. The present paper describes
      methods and procedures utilized to assess the somatomotor conditioned eyeblink
      (EB) response and accompanying visceral changes in human subjects. Methods are
      described for assessing concomitant EB conditioned and unconditioned responses
      and the accompanying heart rate, skin conductance, and respiratory changes during
      Pavlovian conditioning in human subjects. It is stressed that utilization of
      concomitant conditioning of these different response systems may lead to
      inferences regarding the central nervous system structures involved in a variety
      of different kinds of clinical problems.

PMID- 11850038
TI  - In vivo monitoring of amino acids by direct sampling of brain extracellular fluid
      at ultralow flow rates and capillary electrophoresis.
AB  - Extracellular levels of glutamate (GLU), aspartate (ASP), glycine (GLY),
      phosphoethanolamine (PEA), and gamma-aminobutyric acid (GABA) were measured in
      the striatum of anesthetized rats using a novel sampling approach in which
      extracellular fluid (ECF) was removed at 1-50 nl/min using a fused silica
      capillary tube with 18-40 microm inner diameter and a outer diameter of 90
      microm. The samples of ECF were analyzed by capillary electrophoresis with laser
      induced fluorescence detection. Basal levels for GABA, GLY, and GLU measured
      using direct sampling at 1 nl/min were 270 +/- 40, 4950 +/- 1100, and 1760 +/-
      150 nM, respectively in good agreement with the values obtained using
      microdialysis sampling calibrated by the low-flow rate method. ASP levels were
      approximately four-fold higher in directly sampled fluid than in dialysate. At
      higher direct sampling flow rates (10-50 nl/min), detected levels of the amino
      acids were lower by 70-90% indicating depletion of analyte under these
      conditions. PEA, an indicator of membrane disruption, was 5.5-fold higher in
      dialysate than in directly sampled ECF indicating greater tissue damage
      associated with microdialysis. In addition to the basal measurements, the direct
      sampling technique was applied to monitoring concentration changes of GLU and ASP
      in the striatum with better than 90 s temporal resolution after perfusion of
      either 120 mM K(+) or 400 microM L-trans-pyrrolidine-2,4-dicarboxylic acid (PDC)
      through a microdialysis probe immediately adjacent to the direct sampling
      capillary. Levels of GLU and ASP increased 615 +/- 95 and 542 +/- 96%,
      respectively (n=4) upon addition of 120 mM K(+) to the perfusate and 622 +/- 234
      and 672 +/- 218% (n=5) for PDC. It is concluded that direct sampling at low-flow
      rates allows determination of extracellular levels of the amino acids with
      spatial resolution that is at least 500-fold better than microdialysis.

PMID- 11850039
TI  - PC-based visual stimuli for behavioural and electrophysiological studies of optic
      flow field detection.
AB  - A PC-based visual-stimulus-generation package for behavioural and
      electrophysiological studies of responses to optic flow is described. Developed
      for studies of crab vision, the package is particularly well suited for use with
      animals that have very large fields of view, i.e. +/-120 degrees. Programs,
      written in the Borland Delphi language, use the OpenGL graphics library to create
      realistic representations of motion in a three dimensional environment. Large
      field stimuli include simulations of self-motion (rotation and translation,
      separately or in combination) relative to a square-wave grating or other, user
      selected, background. The package also includes representations of approaching
      and receding objects, and rotating spiral patterns for the investigation of
      neural responses to looming/anti-looming. Additionally, the package provides
      local motion stimuli, translating or rotating targets presented at many points in
      the receptive field, which can be used to derive response maps of large-field
      motion-sensitive interneurones. In all these stimuli, inconsistencies in
      animation timing that have hitherto hindered the use of standard PCs running
      Microsoft Windows for such applications have been minimised by using an improved
      real-time clock to control the animation cycle.

PMID- 11850040
TI  - Effective extra-cellular recording from vertebrate neurons in culture using a new
      type of micro-electrode array.
AB  - We describe the fabrication and use of a new type of extracellular micro
      electrode array mounted on a flexible transparent polyimide substrate that can be
      rapidly moved from one part of a culture of vertebrate neurons (rat nodose) to
      another, which permits co-culture of glia under the neurons and is easily and
      rapidly replaceable in the event of damage. The array can be mounted on a
      micromanipulator and moved into place whenever and wherever recordings with or
      without stimulation are needed. The basic electrode system consists of 20-30
      microm diameter gold electrodes, with or without platinisation, exposed to the
      cells through openings in the polyimide and joined to the recording or
      stimulating circuitry through gold tracks embedded in the polyimide. If rigid
      control over neuron placement has been achieved the patterns of electrodes can be
      matched to the neuron positions.

PMID- 11850041
TI  - The application of elastomeric connector for multi-channel electrophysiological
      recordings.
AB  - Interest in recording multi-channel electrophysiological data from behaving
      animals is rapidly growing, and many laboratories tend to record a large number
      of EEG and/or multi-unit channels, despite the limitation of the size of the
      headpiece that a small behaving animal can carry. A common drawback of these
      experiments, therefore, is the relatively large size of even the smallest,
      commercially available, high-density micro-connectors for the headset. To
      overcome this problem, we suggest the application of elastomeric or silicone
      inter-rubber connectors, that are widely used in electronics. The elastomeric or
      "zebra" connector consists of alternating thin strips of layered electrically
      conductive and non-conductive materials. The conductive strips provide electrical
      connections between uninsulated contact surfaces of printed circuit boards such
      as the connector plate of the micro-drive, that holds the brain electrode wires,
      and the preamplifier board of the recording system. In the present paper, we
      provide technical details of the design of this type of connector-sets and
      discuss common issues arising from their use. By comparing the applicability of
      two designs, we aim to demonstrate the simplicity, reliability and durability of
      the elastomeric inter-rubber connectors in electrophysiological experiments on
      freely moving laboratory animals.

PMID- 11850042
TI  - A transcutaneous wire interface for small mammals using an expanded PTFE patch.
AB  - The objective of this paper is to provide the reader with a method of surgical
      implantation of a transcutaneous wire interface for chronic instrumentation of
      small mammals, utilizing a non-bioreactive expanded polytetrafluoroethylene
      (ePTFE) material (W.L. Gore and Associates, Inc., Flagstaff, AZ). We describe the
      implant assembly, as well as details of the surgical implantation, which will
      facilitate successful data acquisition. EMG signal from the implant is of a high
      quality during both rest and activity of the animal and the signal quality is
      maintained up to at least 7 weeks post-implantation without any sign of infection
      or other adverse reaction. This represents an improvement in the viability of
      long-term physiological signal collection via a surgically implanted back plug.

PMID- 11850043
TI  - Temporal transformation of multiunit activity improves identification of single
      motor units.
AB  - This report describes a temporally based method for identifying repetitive firing
      of motor units. This approach is ideally suited to spike trains with negative
      serially correlated inter-spike intervals (ISIs). It can also be applied to spike
      trains in which ISIs exhibit little serial correlation if their coefficient of
      variation (COV) is sufficiently low. Using a novel application of the Hough
      transform, this method (i.e. the modified Hough transform (MHT)) maps motor unit
      action potential (MUAP) firing times into a feature space with ISI and offset
      (defined as the latency from an arbitrary starting time to the first MUAP in the
      train) as dimensions. Each MUAP firing time corresponds to a pattern in the
      feature space that represents all possible MUAP trains with a firing at that
      time. Trains with stable ISIs produce clusters in the feature space, whereas
      randomly firing trains do not. The MHT provides a direct estimate of mean firing
      rate and its variability for the entire data segment, even if several individual
      MUAPs are obscured by firings from other motor units. Addition of this method to
      a shape-based classification approach markedly improved rejection of false
      positives using simulated data and identified spike trains in whole muscle
      electromyographic recordings from rats. The relative independence of the MHT from
      the need to correctly classify individual firings permits a global description of
      stable repetitive firing behavior that is complementary to shape-based approaches
      to MUAP classification.

PMID- 11850044
TI  - High-efficiency adenovirus-mediated in vivo gene transfer into neonatal and adult
      rodent skeletal muscle.
AB  - Several methodological limitations have emerged in the use of viral gene transfer
      into skeletal muscle. First, because the nuclei of mature muscle fibers do not
      undergo division, the use of strategies involving replicative integration of
      exogenous DNA is greatly limited. Another important limitation concerns the
      maturation-dependent loss in muscle fiber infectivity with adenoviral vectors. In
      this study, we investigated the possibility that high-titer infections with
      recombinant adenovirus, expressing a foreign marker gene under the control of a
      strong viral promoter, can significantly improve the efficiency of gene transfer
      in vivo into neonatal and adult rat skeletal muscle. High-titer (2 x 10(10)
      plaque forming units) intramuscular injection of replication-defective adenovirus
      vector, expressing green fluorescent protein (GFP) under the control of
      cytomegalovirus promoter, resulted in GFP expression in 99 +/- 0.34% of fibers in
      the adult soleus muscle and in approximately 85 +/- 1.44% of fibers in the adult
      tibialis anterior muscle. Interestingly, reduction in injected adenoviral dose
      significantly reduced the number of GFP-positive fibers in the adult tibialis
      anterior muscle, but not in the soleus muscle. However, in neonates, adenoviral
      infection resulted in GFP expression in 96-99% of the fibers in the tibialis
      anterior and the gastrocnemius muscles regardless of administered adenoviral
      dose.

PMID- 11850045
TI  - Mirtazapine, but not fluvoxamine, normalizes the blunted REM sleep response to
      clonidine in depressed patients: implications for subsensitivity of alpha(2)
      adrenergic receptors in depression.
AB  - To determine whether alpha(2)-adrenergic receptor (alpha2AR) subsensitivity is a
      state or a trait marker of depression, we consecutively challenged 32 drug-free
      depressed patients with a clonidine REM suppression test (CREST). We then treated
      the patients with fluvoxamine, a selective serotonin reuptake inhibitor, or
      mirtazapine, a selective alpha(2)-adrenergic receptor antagonist. The first 10
      patients from each treatment group who recovered were given a second challenge
      test. The CREST values of the two treatment groups at each time point were
      compared, and also compared with the CREST values of a group of 10 normal
      subjects. Before treatment, the REM sleep response to clonidine in the two groups
      of patients was significantly blunted compared with the REM sleep response in the
      healthy subjects. After treatment, there was still an abnormal REM sleep response
      to clonidine in the fluvoxamine-treated patients, despite clinical recovery, but
      there was a normalized REM sleep response in the mirtazapine-treated patients.
      These results are compatible with the hypothesis that alpha2AR subsensitivity is
      a trait marker of depression and suggest that the effects of these two
      antidepressants on alpha2AR sensitivity may not be linked to the alleviation of
      depression.

PMID- 11850046
TI  - NEO-FFI factor scores as predictors of clinical response to fluoxetine in
      depressed outpatients.
AB  - Research in unipolar depression suggests that neuroticism is associated with poor
      long-term outcome and greater chronicity. The objective of this study was to
      determine whether baseline neuroticism scores predict response to treatment with
      fluoxetine in depressed outpatients. Seventy-six depressed outpatients
      participating in a clinical trial of fluoxetine (fixed/flexible dosing) completed
      the NEO-FFI (five factor inventory short form) at baseline. Clinical response was
      defined as a 50% or greater decrease in the 17-item Hamilton Depression Rating
      Scale (HAM-D-17) total score (final visit--baseline). Logistic regression
      evaluated NEO-FFI factor scores as predictors of treatment outcome within an
      intent-to-treat model. Scores on the neuroticism scale were not found to
      significantly predict treatment response as measured by the HAM-D-17. Strengths
      of this study include a standardized treatment protocol and use of structured
      interview instruments, while limitations include a modest sample size, lack of
      continuation data, state/trait effects, and lack of generalizability to other
      antidepressant treatments.

PMID- 11850047
TI  - Early and delayed personality changes associated with depression recovery? A one
      year follow-up study.
AB  - Many studies have shown the state effect of depression on personality. However,
      the chronology of personality changes associated with depression recovery remains
      unstudied. The objective of this study is to assess early (first month) and
      delayed personality changes associated with depression recovery. Fifty-seven
      depressed inpatients were assessed with the Temperament and Character Inventory
      (TCI) at admission, 1 month, and 1 year post-treatment. Patients were divided
      into poor and favorable outcome. No significant personality change was observed
      in patients with poor depression outcome. Conversely, a favorable outcome of
      depression was associated with early and delayed personality changes. Early
      changes were: decrease in Harm avoidance (HA(1):Worry and pessimism), increase in
      Cooperativeness and Self-directedness (SD(1):Responsibility, SD(4):Self
      acceptance, SD(2):Purposefulness and SD(3):Resourcefulness). Delayed changes were
      changes in character: increase in Self-Directedness (SD(1):Responsibility,
      SD(4):Self-acceptance, SD(5): Congruent second nature), decrease in Self
      transcendence (ST(2):Transpersonal identification). This study shows the
      different status of personality changes associated with depression recovery, and
      it contributes to a better knowledge of the state effect and of subtle clinical
      changes in patients who are recovering from depression. It may also have
      implications for the prediction of depression outcome.

PMID- 11850048
TI  - Cannabis use correlates with schizotypal personality traits in healthy students.
AB  - The literature suggests that cannabis use and schizotypal traits both constitute
      risk factors for the later development of schizophrenia. However, their
      interrelationships remain to be evaluated. The present study examined the
      association between cannabis use and schizotypal traits in 232 healthy students
      who ranged in age from 18 to 25 years. All the students had completed the
      Schizotypal Personality Questionnaire and four of the Chapman Psychosis Proneness
      Scales: the Magical Ideation Scale; the Perceptual Aberration Scale; the Revised
      Physical Anhedonia Scale; and the Revised Social Anhedonia Scale. Subjects were
      divided into three groups according to cannabis use typology: those who had never
      used cannabis, those who were past or occasional users, and those who were
      regular users. Higher scores on the Schizotypal Personality Questionnaire and the
      Magical Ideation Scale characterized the regular and past or occasional users
      compared with those who had never used cannabis. The co-occurrence of cannabis
      use and schizotypal traits appeared to be independent of anxiety and depression
      dimensions. These data suggest that cannabis use and schizotypal traits have to
      be jointly considered in further longitudinal studies of schizophrenia risk
      factors.

PMID- 11850049
TI  - Five-factor personality measures in Chinese university students: effects of one
      child policy?
AB  - Since the one-child policy was implemented in China in 1979, many investigators
      have studied the psychological consequences to children without siblings.
      Although the results are not conclusive, there is evidence that children who have
      siblings, rather than only children, have increased anxiety and depression.
      Whether the differences between students with and without siblings would continue
      when they reached university age is an interesting question. We used the
      Zuckerman-Kuhlman Personality Questionnaire to assess personality traits and the
      Plutchik-van Praag Depression Inventory to measure depressed mood in 134
      university students with and 126 university students without siblings. Most
      students without siblings (93.7%) were reared in urban areas, while 90.3% of
      students with siblings came from rural areas. Parental professions were higher in
      social status and annual family incomes were higher in students without siblings.
      Increased neuroticism-anxiety, aggression-hostility, and depressed mood were
      found in students with siblings. Gender and annual family income were not
      significantly related to personality in the two groups, and birth-order position
      was not related to personality in the students with siblings. In contrast, the
      depression score was positively correlated with neuroticism-anxiety and
      aggression-hostility, but negatively correlated with parental occupation and
      annual family income. The greater competition to receive high education, reduced
      benefits from society, and lower level of social respect might nurture these
      personality traits in students with siblings. These findings might, in some
      limited aspects, indicate that the one-child policy affects personality traits
      and depressed mood in students with siblings.

PMID- 11850050
TI  - Motivation to serve in the military influences vulnerability to future
      posttraumatic stress disorder.
AB  - High motivation and belief in a cause have been reported to be protective against
      posttraumatic stress disorder (PTSD), while below-average intellectual
      functioning and poor educational achievements have been reported to increase
      vulnerability to PTSD. The main goal of this study was to assess the effect of
      education, and intellectual and behavioral functioning on the risk for future
      PTSD. Data collected before exposure to trauma, on intellectual and behavioral
      functioning, and educational achievements of 901 male Israeli adolescents who had
      performed pre-induction screening tests by the Israeli Draft Board, and were
      later diagnosed with PTSD, were compared with a control group of adolescents who
      were not later diagnosed with PTSD. Future PTSD patients had significantly lower
      intelligence, fewer years of formal education and lower scores on a scale
      assessing motivation to serve in the military, in comparison with the control
      group, with effect sizes (ES) ranging from 0.14-0.34. In contrast, future PTSD
      patients scored significantly higher on a scale assessing social functioning,
      ES=0.13. However, when controlling for the differences in motivation to serve,
      all of these differences disappeared. In this cohort, although slightly below
      average intellectual functioning and formal education, and better social
      functioning, independently increased vulnerability to suffer from PTSD, these
      associations disappeared when the future PTSD patients' lower motivation to serve
      in the military was included in the analysis. This suggests that low motivation
      to serve in the military might increase vulnerability for PTSD.

PMID- 11850051
TI  - Case identification of depression with self-report questionnaires.
AB  - Many self-report measures that are used to identify cases of depression are
      symptom severity measures that are adopted for diagnostic purposes by use of
      cutoff scores. A troublesome problem with this approach is that optimal cutoff
      scores often vary across studies, which increases the difficulty of cross-study
      comparisons. This study evaluated the performance of a DSM-IV based depression
      screening scale, the Diagnostic Inventory for Depression. We compared the
      diagnostic performance of two different approaches to scoring the DID: a cutoff
      scoring approach and a standardized DSM-IV symptom-summation algorithm. Clinical
      diagnosis based on a semi-structured interview was the standard of comparison.
      Receiver operating characteristic (ROC) analysis indicated that a DID cutoff
      score performed comparably to the DID algorithmic approach in identifying cases.
      This finding is in contrast to prior research which suggested that algorithmic
      approaches might improve test performance over the cutoff score approach. The
      manner by which a user might choose the appropriate scale-scoring method for case
      identification is discussed.

PMID- 11850052
TI  - Measurement adequacy of the CES-D among a sample of older African-Americans.
AB  - This manuscript examines the measurement adequacy of the CES-D when applied in
      older African-Americans (n=227). The response distribution was skewed towards
      less symptomatology on all items, and the internal consistency of the CES-D was
      acceptable (alpha=0.86). An exploratory factor analysis revealed four underlying
      factors of depressive symptomatology: (1) depressive/somatic; (2) positive; (3)
      interpersonal; and (4) social well-being. The primary factor was a combination of
      depression and somatic symptoms, a commonly reported uni-dimensional factor among
      ethnic groups. Additionally, a fourth factor emerged that has not previously been
      identified, labeled 'social well-being'. This factor consisted of three items
      that may tap into the social interactions of the elderly: appetite, hopeful, and
      talk. These findings contribute to the growing body of evidence on the unique
      measurement properties of the CES-D across diverse populations.

PMID- 11850053
TI  - The early-onset fearful panic attack as a predictor of severe psychopathology.
AB  - The objective of this study was to replicate previous findings indicating that
      early-onset panic attack (< or =20 years) with fear represents a possible
      prodrome of early-onset severe psychopathology. Data were drawn from the
      Epidemiologic Catchment Area Survey (ECA) (n=20 291), a household sample of
      adults aged 18 and older drawn from five cities in the United States.
      Multivariate logistic regression analyses were used to differentiate those with
      early-onset panic attacks with fear from those with other panic attacks (early
      onset without fear, late-onset without fear, late-onset with fear) with regard to
      psychiatric comorbidity, age at onset of comorbid mental disorders, and suicidal
      ideation and suicide attempts. Results of statistical analyses revealed that
      early-onset fearful panic attack (n=368) was associated with increased likelihood
      of major affective and substance use disorders, significantly earlier onset of
      comorbid mental disorders, higher rates of suicidal ideation and suicide attempt,
      and higher rates of antisocial personality disorder compared with those with
      other subtypes of panic attacks. Multiple logistic regression analyses showed
      that early-onset fearful panic was independently associated with increased odds
      of major depression [OR=3.0 (2.6, 3.5)], bipolar disorder [OR=7.9 (5.7, 10.8)],
      antisocial personality disorder [OR=1.5 (1.3, 1.7)], agoraphobia [OR=1.2 (1.1,
      1.4)], simple phobia [OR=1.6 (1.4, 1.8)], and alcohol dependence [OR=1.3 (1.2,
      1.5)], compared with those with all other panic attacks. These findings are
      consistent with previous epidemiologic data and provide new evidence to suggest
      that early-onset fearful panic attack may be a marker of increased vulnerability
      to severe and persistent psychopathology and associated with high rates of
      suicidality.

PMID- 11850054
TI  - Heart rate time series: decreased chaos after intravenous lactate and increased
      non-linearity after isoproterenol in normal subjects.
AB  - In this study, we reanalyzed our previous heart rate time series data on the
      effects of intravenous sodium lactate (n=9) and intravenous isoproterenol (n=11)
      using non-linear techniques. Our prior findings of significantly higher baseline
      non-linear scores (NL: S(netGS)) and significantly lower largest Lyapunov
      exponents in supine posture in patients with panic disorder compared to control
      subjects prompted this study. We obtained the largest Lyapunov exponent (LLE),
      and a measure of non-linearity (NL: S(netGS)) of heart rate time series. LLE
      quantifies predictability and NL quantifies the deviation from linear processes.
      There was a significant increase in NL score, (S(netGS)) after isoproterenol
      infusions and a significant decrease in LLE (an increase in predictability
      indicating decreased chaos), after intravenous lactate in supine posture in
      normal control subjects. Increased NL scores in supine posture after intravenous
      isoproterenol may be due to a relative increase in cardiac sympathetic activity
      or a decrease in vagal activity at least in certain circumstances, and an overall
      decrease in LLE may indicate an impaired cardiac autonomic flexibility after
      intravenous sodium lactate, as LLE is diminished by autonomic blockade by
      atropine. Band analysis of LLE (LF/HF) (LF: 0.04-0.15 Hz and HF: 0.15-0.5 Hz)
      showed an increase of these ratios during either condition with a higher
      sympathovagal interaction after the drug administration. These findings may throw
      new light on the association of anxiety and significant cardiovascular events.

PMID- 11850055
TI  - Lack of evidence for associations between plasma platelet-activating factor
      acetylhydrolase deficiency and schizophrenia.
AB  - Platelet-activating factor (PAF) is a potent phospholipid mediator that plays
      various roles in neuronal function and brain development. It is involved in NMDA
      receptor function. Release and degradation of PAF is controlled by intracellular
      and plasma PAF-acetylhydrolase (PAFAH). The plasma PAFAH gene (PLA2G7) is located
      on chromosome 6p. A previous study showed weak associations of the Ile198Thr and
      Val379Ala polymorphisms of this gene with schizophrenia that did not reach
      statistical significance after correction for multiple comparisons. Another study
      showed that a functional alteration of the enzyme with these two polymorphisms is
      likely, but the magnitude may be modest. Approximately 4% of the Japanese
      population lack plasma PAFAH because of a loss-of-function mutation (Val279Phe)
      in the PAFAH gene. Thus, the Val279Phe mutation is useful for examining whether a
      causal relation exists between PAFAH function and schizophrenia. We looked for an
      association between the Val279Phe mutation and schizophrenia in 191 Japanese
      patients with schizophrenia and in 188 Japanese controls. Similar genotypic and
      allelic distributions were observed in the two groups. These observations
      indicate that functional differences in the plasma form of PAFAH do not play a
      substantial role in the etiology of schizophrenia. However, the present study
      leaves open the possibility that other isoforms are involved.

PMID- 11850056
TI  - Apathy syndrome in cocaine dependence.
AB  - The cocaine abstinence syndrome has been associated with a range of symptoms,
      including apathy and depression. Although initial studies reported high
      prevalence rates of 'apathy/amotivation' and depression, validated rating scales
      of apathy were not then available. Using a validated measure of apathy, we
      hypothesized that newly abstinent cocaine-dependent subjects would report
      increased apathy compared with non-cocaine-using control subjects. Furthermore,
      because apathy and depression are dissociable in other neuropsychiatric
      syndromes, we examined whether they were dissociable in recently abstinent
      cocaine-dependent subjects. Following 4 days of monitored abstinence, cocaine
      dependent subjects (n=11) and non-drug-using control subjects (n=19) were
      administered standardized tests of apathy and depression. Cocaine-dependent
      subjects had elevated scores on the apathy rating scale compared with the control
      group, but the groups did not differ in ratings of depression. These data suggest
      that apathy is present during the initial phases of abstinence for a subset of
      cocaine-dependent individuals. This group may benefit from targeted
      pharmacological intervention.

PMID- 11850057
TI  - Prevalence of body dysmorphic disorder in a German college student sample.
AB  - The prevalence of body dysmorphic disorder (BDD) was investigated in a non
      clinical sample. German college students (n=133; 73.7% female) completed self
      report questionnaires assessing BDD, self-esteem, symptoms of depression,
      obsessive-compulsive disorder and skin picking. Based on our data, seven
      participants (5.3%) satisfied DSM-IV BDD criteria. Significant differences were
      found between students with and without BDD in the number of endorsed obsessive
      compulsive disorder symptoms. Poor body image was associated with poor self
      esteem, symptoms of depression and obsessive-compulsive disorder. One student
      with BDD also reported severe skin picking. In conclusion, BDD is a common
      psychiatric disorder in college students.

PMID- 11850058
TI  - Maternal deprivation increases cell death in the infant rat brain.
AB  - Prolonged separation from the mother can interfere with normal growth and
      development and is a significant risk factor for adult psychopathology. In
      rodents, separation of a pup from its mother increases the behavioral and
      endocrine responses to stress for the lifetime of the animal. Here we
      investigated whether maternal deprivation could affect brain development of
      infant rats via changes in the rate of cell death as measured by labeling the 3'
      end of DNA fragments using terminal transferase (ApopTag). At postnatal day 12
      (P12), the number of cells undergoing cell death approximately doubled in the
      cerebral cortex, cerebellar cortex and in several white matter tracts following
      24 h of maternal deprivation. Deprivation strongly increased the number of
      ApopTag-labeled cells at P6 but not at P20. Stroking the infant rats only
      partially reversed the effects of maternal deprivation. Increased cell death in
      white matter tracts correlated with an induction of nerve growth factor which has
      been previously associated with oligodendrocyte cell death. Cell birth was either
      unchanged or decreased in response to deprivation. These results indicate that
      maternal deprivation can alter normal brain development by increasing cell death
      of neurons and glia, and provides a potential mechanism by which early
      environmental stressors may influence subsequent behavior.

PMID- 11850059
TI  - Ontogenic modifications in the effect of the GABAergic system on the hypothalamic
      excitatory amino acids: its relationship with GABAergic control of gonadotrophin
      secretion during sexual maturation in female rats.
AB  - Aminooxyacetic acid (AOAA), an inhibitor of gamma-aminobutyric transaminase,
      stimulates the in vitro GABA release by medial and anterior preoptic hypothalamic
      areas in prepubertal female rats (6, 15 and 30 days of age). This increase of
      GABA release at 15 days of age, was accompanied by a significant increase
      (P<0.01) in the hypothalamic release of glutamate (GLU) and aspartate (ASP), the
      excitatory amino acids involved in N-methyl-D-aspartate neurotransmission and a
      decrease in the release of these excitatory amino acids at 6 and 30 days of age
      (P<0.01). The increase in the hypothalamic release of GLU and ASP at 15 days of
      age was accompanied by a significant increase of the plasmatic LH and FSH
      concentration, while the hypothalamic decrease of excitatory amino acids release
      induced by AOAA also decreased LH and FSH plasmatic levels at 6 and 30 days of
      age. In summary, the present results show that in female rats there are
      differences in the effect of GABAergic system the hypothalamic release of GLU and
      ASP and on gonadotrophin secretion at different ages of prepubertal period, i.e.
      an inhibitory effect at 6 and 30 days of age and a stimulatory one at 15 days of
      age. It is proposed that the different effects of GABA on gonadotrophin secretion
      in prepubertal rats previously described are connected with ontogenic changes in
      the interrelationships between GABAergic and NMDA neurotransmission systems
      during sexual maturation of the hypothalamus in female rats. It is probable that
      these ontogenic modifications are connected with the maturation of interneuronal
      connection and/or new receptors activity.

PMID- 11850060
TI  - Nicotine exposure during a postnatal critical period alters NR2A and NR2B mRNA
      expression in rat auditory forebrain.
AB  - Chronic nicotine exposure (CNE) can alter brain development and is thought to
      produce deficits in auditory function. Previously, we found that CNE during the
      second postnatal week, but not before or after, increases the duration of
      excitatory postsynaptic potentials (EPSPs) mediated by N-methyl-D-aspartate
      receptors (NMDARs) in rat auditory cortex. It was proposed that a potential
      mechanism underlying increased EPSP duration could be over-stimulation of
      presynaptic nicotinic acetylcholine receptors, leading to prolonged glutamate
      release. Since glutamatergic activity regulates levels of postsynaptic NMDAR
      subunits, here we examine the effects of CNE on mRNA expression for the NR2A and
      NR2B subunits in auditory cortex and thalamus. Two days of CNE (postnatal days 8
      9), produced no effects, but 5 days (postnatal days 8-12) enhanced cortical NR2A
      mRNA levels and reduced thalamic NR2B mRNA levels for up to 2 weeks. These
      effects are consistent with the hypothesis that CNE during a postnatal critical
      period disrupts auditory cortex development by over-stimulating glutamatergic
      synapses.

PMID- 11850061
TI  - Lipopolysaccharide (LPS)-induced dopamine cell loss in culture: roles of tumor
      necrosis factor-alpha, interleukin-1beta, and nitric oxide.
AB  - Parkinson's disease (PD) is a neurodegenerative disorder characterized by the
      loss of dopamine (DA) neurons of the substantia nigra pars compacta (SNc).
      Although the exact mechanisms responsible for this cell loss are unclear,
      emerging evidence suggests the involvement of inflammatory events. In the present
      study, we characterized the effects of the proinflammatory bacteriotoxin
      lipopolysaccharide (LPS) on the number of tyrosine hydroxylase immunoreactive
      (THir) cells (used as an index for DA neurons) in primary mesencephalic cultures.
      LPS (10-80 microg/ml) selectively decreased THir cells and increased culture
      media levels of interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF
      alpha) as well as nitrite (an index of nitric oxide (NO) production). Cultures
      exposed to both LPS and neutralizing antibodies to IL-1beta or TNF-alpha showed
      an attenuation of the LPS-induced THir cell loss by at least 50% in both cases.
      Inhibition of the inducible form of nitric oxide synthase (iNOS) by L-NIL did not
      affect LPS toxicity, but increased the LPS-induced levels of both TNF-alpha and
      IL-1beta. These findings suggest that neuroinflammatory stimuli which lead to
      elevations in cytokines may induce DA neuron cell loss in a NO-independent manner
      and contribute to PD pathogenesis.

PMID- 11850062
TI  - Generation of tyrosine hydroxylase-immunoreactive neurons in ventral
      mesencephalic tissue of Nurr1 deficient mice.
AB  - Nurr1 is an orphan nuclear receptor belonging to the family of evolutionary
      conserved steroid/thyroid hormone receptors. It has been shown that Nurr1 is
      required for development of ventral mesencephalic dopaminergic cells in vivo and
      that Nurr1 regulates the tyrosine hydroxylase (TH) gene. The aim of this study
      was to investigate the possibility of finding ventral mesencephalic TH-positive
      neurons in Nurr1 deficient tissue when developed in the presence of wild type
      (WT) striatum. Therefore, fetal ventral mesencephalic tissue from embryonic day
      (E) 9.5-10.5 fetuses from Nurr1 mutant mice was co-cultured with lateral
      ganglionic eminence (LGE) from WT fetuses using the 'roller-drum' culture
      technique. TH-immunohistochemistry revealed similar number of positive neurons in
      WT, heterozygous, and Nurr1 deficient tissue, respectively. When ventral
      mesencephalon, dissected from E10.5 fetuses, was cultured alone without the
      presence of LGE, significantly more TH-immunoreactive neurons were found in WT
      and Nurr1 +/- than that seen in Nurr1 -/- cultures. In single ventral
      mesencephalic cultures dissected from E15.5, TH-positive neurons were found in
      all tissue cultures derived from knockout animals. Interestingly, the formation
      of TH-positive nerve fiber bundles was obvious in WT cultures while not observed
      in cultures of knockout tissue. When ventral mesencephalon was cultured alone in
      serum-free medium, almost no TH-positive neurons were found in cultures of
      knockout tissue. The addition of the growth factors epidermal growth factor and
      fibroblast growth factor-8 did not induce TH-immunoreactivity in serum-free Nurr1
      -/- tissue cultures. In conclusion, TH-positive neurons may be generated in
      ventral mesencephalic tissue of Nurr1 deficient mice, suggesting that Nurr1 is
      not required for TH gene expression in ventral midbrain in vitro.

PMID- 11850063
TI  - Asymmetric segregation of mitochondria and mortalin correlates with the multi
      lineage potential of inner ear sensory cell progenitors in vitro.
AB  - The sensory epithelia of the inner ear include hair cells and supporting cells
      that share a common precursor. One possible mechanism involved in the genesis of
      these cell types is through asymmetric cell division. In this work we have
      studied asymmetric division of inner ear sensory cell progenitors in vitro in an
      attempt to understand how the different cell phenotypes are generated. In the
      search for molecules that will segregate asymmetrically we have found that
      mitochondria in general, and a mitochondrial protein named mortalin in
      particular, are asymmetrically segregated during certain cell divisions. In one
      conditionally immortal cell line (UB/OC-1), which represents a population of
      committed hair cell precursors, mortalin is uniformly distributed in the
      cytoplasm and shared equally between sibling cells during division. In another
      cell line (UB/UE-1), which represents a bipotent, vestibular supporting cell that
      can produce both neonatal hair cells as well as supporting cells, mortalin
      segregates asymmetrically. In UB/UE-1, approximately 12% of the cells display an
      asymmetric distribution of mortalin and mitochondria. The proportion of
      asymmetric cells increases immediately after the release of the immortalizing
      gene and before the onset of differentiation. The asymmetric segregation of
      mortalin in the bipotent cell line and its uniform distribution in a committed,
      lineage-restricted cell line raises the possibility that it may play a role in
      cell fate determination.

PMID- 11850064
TI  - Opposing changes of trimeric G protein levels during ontogenetic development of
      rat brain.
AB  - Developmental changes in the distribution of guanine nucleotide-binding
      regulatory proteins (G proteins) were investigated in the rat brain during
      postnatal development. Using a standard or high-resolution urea-SDS-PAGE and
      specific polyclonal antipeptide antibodies oriented against
      G(i)alpha1/G(i)alpha2, G(i)alpha3, G(s)alpha, G(o)alpha1/G(o)alpha2,
      G(q)alpha/G(11)alpha and Gbeta subunit, all these proteins were determined by
      quantitative immunoblotting in homogenates prepared from cortex, thalamus,
      hippocampus and pituitary of 1-, 7-, 12-, 18-, 25- and 90-day-old animals. The
      levels of the majority of G protein alpha subunits, namely G(i)alpha1,
      G(i)alpha2, G(i)alpha3, G(o)alpha1, G(o)alpha2, G(q)alpha, G(11)alpha and Gbeta,
      were high already at birth. Whereas the short variant of G(s)alpha, G(s)alphaS,
      rose sharply in all tested brain regions between postnatal day (PD) 1 and 90, the
      long variant of G(s)alpha, G(s)alphaL, was unchanged in cortex and thalamus and
      slightly increased in hippocampus. An increase was observed also in expression of
      G(i)alpha1/G(i)alpha2 and G(o)alpha1 protein, while G(o)alpha2 remained constant.
      Minority protein G(o)alpha* dramatically increased in cortex and thalamus, was
      unchanged in hippocampus and not detectable in pituitary. By contrast, the
      highest levels of G(i)alpha3 and G(q)alpha/G(11)alpha were detected as early as
      at PD 1. During the next 90 days, the immunological signal of G(i)alpha3 almost
      disappeared and G(q)alpha/G(11)alpha continuously declined to the levels
      corresponding to 50% of the levels determined at birth. Expression of Gbeta
      subunit was basically unchanged during postnatal development. Our present
      analysis indicates that G(s)alpha, G(i)alpha/G(o)alpha and G(q)alpha/G(11)alpha
      proteins are differently expressed in the course of brain development.
      Differential expression of the individual alpha subunits of trimeric G proteins
      during postnatal development suggests their different roles in maturation of the
      brain tissue.

PMID- 11850065
TI  - Ontogenetic development of the G protein-mediated adenylyl cyclase signalling in
      rat brain.
AB  - Maturation of the brain adenylyl cyclase (AC) signalling system was investigated
      in the developing rat cortex, thalamus and hippocampus. Expression of AC type II,
      IV and VI measured by Western blot dramatically increased in all tested brain
      regions during the first 3 weeks after birth and these levels were maintained in
      adulthood. AC type I did not change during ontogenesis. In parallel, AC enzyme
      activities were determined in order to obtain the functional correlates to the
      preceding structural (immunoblot) analyses of trimeric G proteins [Ihnatovych et
      al., Dev. Brain Res. (2002) in press]. Surprisingly, basal, manganese-, fluoride
      , forskolin- and GTP-stimulated adenylyl cyclase developed similarly. The
      relatively low enzyme activities, which were determined at birth, progressively
      increased (about four times) to a clear maximum around postnatal day PD 12. This
      was followed by a progressive regression to adulthood so that activity of AC at
      PD 90 was comparable with the low neonatal level. The peak of AC activities at PD
      12 was detected in all tested brain regions. Stimulatory (isoproterenol) effect
      on basal AC activity as well as inhibitory (baclofen) effect on forskolin
      stimulated AC activity were unchanged between PD 12 and PD 90. Thus, comparison
      of results of the structural and functional analyses of adenylyl cyclase
      signalling system revealed a clear dissociation between the increase in the
      amount protein of various AC isoforms and the decrease of total G-protein
      mediated enzyme activities between PD 12 and adulthood. As none of the complex
      changes in trimeric G protein levels can explain this difference, the future
      research has to be oriented to identification of potential negative regulators of
      AC in the course of brain development. Among these, the newly discovered group of
      GTPase activating proteins, RGS, appears to be of primary importance because
      these proteins represent potent negative regulators of any G protein-mediated
      signalling in brain.

PMID- 11850066
TI  - Coordinate expression of beta1 integrins and their regulator, TGF beta2 at the
      floor plate of the medulla oblongata is correlated with the crossing of the
      fibers of olivocerebellar projection in mice.
AB  - During embryonic day 11 (E11) to E16, contact-dependent interacting molecules
      beta1 integrins and their putative regulator TGF beta2 are coordinately expressed
      at the floor plate in the caudal part of mouse myelencephalon. Their expression
      disappears at E18. Consistent with the peak of their expression (E13-E16),
      olivocerebellar fibers primarily cross the floor plate. These data indicate that
      spatiotemporal expression of beta1 integrins and TGF beta2 is correlated with the
      crossing of olivocerebellar fibers.

PMID- 11850068
TI  - Predominance of trisomy 1q in myelodysplastic syndromes in Korea: is there an
      ethnic difference? A 3-year multi-center study.
AB  - A predominance of total or partial chromosomal losses and the rarity of
      translocations are characteristics of myelodysplastic syndrome (MDS), and 5q,-5, 
      7 and +8 are known to be the most predominant chromosomal changes. To investigate
      whether the incidence and the pattern of chromosomal changes in MDS varies by
      location in Korea, we reviewed the cytogenetic results of 205 MDS cases from
      three medical centers. Distribution of MDS subtypes and the incidence of
      chromosomal aberration (44.8%) of MDS in Korea were similar to those found in
      other countries, however, their patterns were different. Translocations (40.4%)
      predominated over partial or total deletions (36.3%) in Korea. The most common
      abnormalities in MDS were trisomy 8, trisomy 1q, -5/5q-, and -7/7q-, which
      occurred in 18(19.5%), 14(15.2%), 12(13.0%), and 11(11.9%) patients,
      respectively. It is of note that trisomy 1q, which is rarely reported in
      hematologic malignancies, was the second most common change associated with MDS
      in Korea, and that structural anomalies of chromosomes 1(19.6%) exceeded that of
      chromosome 5(15.2%). The most common sole anomalies were trisomy 8(7.6%) and
      14(78%) of 18 cases with chromosome 1 anomalies accompanied by other chromosomal
      abnormalities, suggesting that the changes of chromosome 1 may be evolutionary
      events rather than sporadic events. In conclusion, trisomy 1q and trisomy 8
      predominate in Korean MDS, suggesting the likelihood of ethnic differences.

PMID- 11850067
TI  - Karyotypic heterogeneity and clonal evolution in squamous cell carcinomas of the
      head and neck.
AB  - Head and neck squamous cell carcinomas (HNSCC) are often characterized by complex
      karyotypic changes, and a substantial proportion of the reported tumors have
      shown intratumor heterogeneity in the form of cytogenetically related (40%) or
      unrelated clones (20%). In order to study intratumor heterogeneity and to
      distinguish the temporal order of chromosome rearrangements in these tumors, two
      or more samples from different areas of the same tumor were separately examined
      in 19 HNSCC, yielding karyotypes from a total of 42 tumor samples. Intrasample
      heterogeneity was observed in 16 samples. Two samples displayed both related and
      unrelated multiple clones, four samples showed only multiple unrelated clones,
      and the remaining 10 samples had only related subclones. Intersample
      heterogeneity was detected in all but one tumor. Five tumors showed both
      cytogenetically related and unrelated multiple clones, 11 were found to have only
      related subclones, and the remaining two tumors showed only unrelated clones.
      Clonal evolution could be assessed in 13 tumors. A comparison of chromosome
      imbalances in different subclones from these tumors suggests that partial or
      entire loss of 3p, 8p, 9p, and 18q and gain of genetic material from 3q and 8q
      are likely to be early genetic events. In contrast, loss of 1q, 6p, 7q, and
      chromosome 10, as well as gain of chromosome arms 5p and 7p, are most probably
      later genetic events. One of the examined tumors contained two highly complex
      clones that were cytogenetically unrelated, indicating that this tumor had a
      multicellular origin.

PMID- 11850069
TI  - Overrepresentation of 17q22-qter and 22q13 in dermatofibrosarcoma protuberans but
      not in dermatofibroma: a comparative genomic hybridization study.
AB  - Histopathological differentiation between dermatofibrosarcoma protuberans (DFSP)
      and dermatofibroma (DF) is often difficult, because both neoplasms share some
      clinical features and the presence of a storiform pattern. In the present study,
      we investigated the usefulness of comparative genomic hybridization (CGH) in the
      diagnosis of these entities by examining 12 DFSP and 12 DF cases. The most
      frequent DNA sequence copy number changes detected in 10 (83%) of 12 DFSP cases
      (mean, 1.9 aberrations/tumor; range, 0-3) consisted of gains of 17q22-qter (10
      tumors), 22q13 (nine tumors), and 8q24.1-qter (three tumors). High-level
      amplification, which was detected in three tumors, was seen only in chromosome
      17, with 17q23-q25 as the minimal common region. Loss of DNA sequences was not
      found in DFSP cases. In contrast, two (17%) of the 12 DF cases (mean, 0.5
      aberrations/tumor; range, 0-4) showed DNA sequence copy number changes, although
      recurrent gains and losses and high-level amplifications were not observed. Gains
      were more common than losses in DF. Overrepresentation of 17q and 22q sequences
      was a common finding in DFSP but not in DF. Thus, CGH seems to be useful for
      distinguishing DFSP from DF in most cases.

PMID- 11850070
TI  - A t(4;11)(q21;p15) in a case of T-cell lymphoma and a case of acute myelogenous
      leukemia.
AB  - The translocation (4;11)(q21;p15) has been observed in acute lymphoblastic as
      well as acute myeloid leukemias (ALL and AML, respectively). We report the first
      case of T-cell lymphoma with t(4;11)(q21;p15) and a case of AML. The clinical
      history of and cytogenetics in the latter is suggestive of a secondary leukemia;
      his karyotype revealed emergence of a t(3;11)(q21;q13) in addition to the
      t(4;11). Previously reported cases with t(4;11)(q21;p15) are reviewed, clinical
      and morphological characteristics of cases with t(4;11)(q21;q23) and
      t(4;11)(q21;p15) are compared, and chromosome abnormalities involving the NUP98
      gene in hematologic malignant disorders are reviewed.

PMID- 11850071
TI  - Absence of evidence for HER2 amplification in nasopharyngeal carcinoma.
AB  - HER2 (c-erbB-2) has been suggested to be a prognostic factor in a variety of
      human cancers including breast, gastric and ovarian cancers. This study is
      therefore designed to identify changes of HER2 in nasopharyngeal carcinoma (NPC),
      an epithelia-derived malignancy with strong racial and geographic distribution.
      Interphase FISH and immunohistochemical (IHC) staining were used to analyze the
      gene copy number and protein expression of HER2 in 45 cases of NPC from
      Guangzhou, Southern China, an area with the highest incidence of NPC in the
      world. Our results, however, found no significant alterations in gene copy number
      for HER2, although IHC staining detected expression of HER2 oncoprotein in 33% of
      the 45 NPC tumors. No correlation was observed between HER2 expression and sex,
      age and clinical outcome of the patients, T stage, lymph node status, site and
      histopathological grading of the tumors. These results cast doubt on the value of
      HER2 as a prognostic factor for NPC.

PMID- 11850072
TI  - A comprehensive karyotypic analysis on a newly established sarcomatoid
      hepatocellular carcinoma cell line SH-J1 by comparative genomic hybridization and
      chromosome painting.
AB  - We first established a sarcomatoid hepatocellular carcinoma cell line, designated
      as SH-J1, and applied comparative genomic hybridization and fluorescence in situ
      hybridization (FISH) with chromosome painting probes for the characterization of
      the chromosomal rearrangements. In the SH-J1 cell line, the pleomorphic spindle
      cells were arranged in bundles of interlacing patterns and were positive in
      immunohistochemical staining with hepatocyte-related markers. By G-banding and
      FISH, the chromosomal gains were detected at 6p and 17, whereas losses were
      observed at 3p21-pter, 3q27-qter, 4, 6q, 13pter-q11, 16, 18, 19p13, and Y.

PMID- 11850073
TI  - Cytogenetic characterization of diffuse large cell lymphoma using multi-color
      fluorescence in situ hybridization.
AB  - We have employed multi-color fluorescence in situ hybridization (M-FISH) to
      characterize the cytogenetic changes in 20 diffuse large B-cell lymphomas
      (DLBCL), that contained complex and partially characterized karyotypes. The M
      FISH analysis helped to delineate 94% of the unidentified abnormalities and
      assisted in redefining some unidentified/misidentified karyotypic changes.
      Recurrent breakpoints observed in approximately 20% cases included 14q32, 3p21,
      3q27, 22q12, 1q25, and 18q21 (in decreasing order), and 1p22, 1q21, 4q31, 6q21,
      and 8q24 (in four cases each). Numerical gain of chromosomes 7, 9, 12, and X and
      loss of chromosomes 1, 4, 6, 17, and Y, were noted in approximately 20% of cases.
      The minimum deleted regions encompassed 6q21-q25, 1p22-p36, 1q32-q44, 2p23-p25,
      4q31-q35, 13p13-q14, and 17p11-p13. Two cases presented with a sole structural
      abnormality, and one contained a der(17)t(9;17)(p21;p13), which has not been
      reported earlier as a sole abnormality in DLBCL. Upon completely characterizing
      the karyotypes, we observed with interesting that in 55% of the cases, more than
      one BCL gene bearing regions was involved in translocations. In the remaining
      45%, where only one or none of the BCL gene regions was involved in a
      rearrangement, we observed the loss of chromosomes 6 and/or 17 or partial
      deletions of 6q and/or 17p or gain of 7 and/or 12. Our findings suggest that,
      although BCL2 and BCL6 are most often implicated in DLBCL, the possibility of the
      disruptions of BCL3, BCL8, BCL9, and BCL10 as a "primary event" in DLBCL cannot
      be ruled out. Most often, a combination of events may be necessary for the
      genesis of DLBCL or progression of follicular lymphoma to DLBCL. Overall, M-FISH
      has enhanced our ability to provide a comprehensive karyotypic analysis, and has
      helped in defining the importance of BCL3, BCL8, BCL9, and BCL10 carrying
      breakpoints in DLBCL.

PMID- 11850074
TI  - t(8;21;14)(q22;q22;q24) is a novel variant of t(8;21) with chimeric transcripts
      of AML1-ETO in acute myelogenous leukemia.
AB  - We report a male patient with acute myelogenous leukemia (AML; French-American
      British M2) associated with AML1-ETO. Cytogenetic studies showed a complex
      karyotype including a novel translocation (8;21;14)(q22;q22;q24) in all analyzed
      cells. This three-way translocation was confirmed with spectral karyotyping.
      Reverse transcription-polymerase chain reaction analysis for AML1-ETO chimeric
      transcripts showed the presence of the fusion product with the expected size.
      Translocation (8;21;14)(q22;q22;q24) is a novel variant of t(8;21)(q22;q22),
      possibly having a common molecular pathogenetic mechanism.

PMID- 11850075
TI  - Complex t(X;18)(p11.2;q11.2) with a pericentric inversion of the X chromosome in
      an adolescent boy with synovial sarcoma.
AB  - Synovial sarcoma is the most common nonrhabdomyosarcomatous soft-tissue sarcoma
      in children and young adults. It is characterized by the common
      t(X;18)(p11.2;q11.2) that results in the fusion of SYT on chromosome 18 to one of
      two closely related and adjacent genes on the X chromosome, SSX1 or SSX2. Here we
      describe a poorly differentiated, monophasic synovial sarcoma in a 17-year-old
      adolescent boy. Hyperdiploidy, a t(X;18)(q13;q11), and other structural
      abnormalities were detected by conventional cytogenetic analysis. Fluorescence in
      situ hybridization with the PAC probe RP3-519N18, which is specific for the Xp11
      region, resulted in a signal on the der(Xq), a finding consistent with a
      pericentric inversion of the X chromosome that resulted in a
      t(X;18)(p11.2;q11.2)inv(X)(p11.2q13). Real-time polymerase chain reaction using
      primer sets specific for SYT-SSX1 and SYT-SSX2 confirmed the presence of an SYT
      SSX1 fusion transcript. Our finding of this unique and complex translocation in
      synovial sarcoma demonstrates the utility of molecular methods in confirming the
      diagnosis of synovial sarcoma.

PMID- 11850076
TI  - Fluorescence in situ hybridization analysis of HER-2/neu in brushings of normal
      oral mucosa.
AB  - Oncogene alterations have been clearly demonstrated to be related to the
      carcinogenesis and progression of oral squamous cell carcinoma (OSCC). However,
      the analysis of these alterations for screening and early diagnostic purposes
      generally requires invasive techniques for surgical removal of pathological
      epithelium. The aim of the present study was to assess the feasibility of
      fluorescence in situ hybridization (FISH) analysis of HER-2/neu amplification in
      oral mucosa brushings and to compare the HER-2/neu status with the history and
      smoking and drinking habits of healthy subjects. Cells obtained by centrifugation
      of oral brushings from 21 subjects (overall no. of cells: 5125) were suspended in
      physiological saline and fixed onto two slides for cytological evaluation and
      FISH analysis (dual-target, dual-color fluorescence assay) of the HER-2/neu gene
      and CEP17 centromere. A mean of 89.8% of the cells showed two HER-2/neu signals
      and a mean of 94% had two CEP17 signals at fluorescent microscopy. Finally, a
      mean of 96% of cells with HER-2/neu / CEP17 had a ratio equal to 1. No
      association between smoking and drinking habits, age and the HER-2/neu and CEP17
      characteristics evaluated by FISH was found.

PMID- 11850078
TI  - Complex karyotype in a low grade phyllodes tumor of the breast.
AB  - Cytogenetic analysis of a phyllodes tumor of low grade malignancy disclosed the
      karyotype 52-55,XX, -1,+5,+7,+9,+10,+11,-15,+18,
      19,+20,der(21)t(1;21)(p13;q22),+mar1x 2-4,+mar2[cp18]/46,XX. This study shows
      that a complex chromosome karyotype can be found in low-grade phyllodes tumors
      and is not necessarily a sign of extreme malignancy of these neoplasms.

PMID- 11850077
TI  - Interstitial deletion of 20q in a patient with Waldenstrom macroglobulinemia
      following chemotherapy.
AB  - A 76-year-old male with a history of renal insufficiency was found to have
      anemia, an IgM kappa paraprotein on serum immunofixation studies, absence of
      lytic bone lesions, and findings in the bone marrow consistent with Waldenstrom
      macroglobulinemia (WM). Cytogenetic studies including fluorescence in situ
      hybridization (FISH) on the post-treatment bone marrow revealed the karyotype
      46,XY,del(20)(q13.1q13.3). Less than 70 cases of karyotypic abnormalities in
      patients with WM have been reported, which have shown no abnormalities specific
      to WM. Monosomy or trisomy of chromosome 20 has been reported in approximately
      eight cases, but to our knowledge this is the first case report of an
      interstitial deletion of 20q, confirmed by FISH using chromosome 20 subtelomeric
      specific probes. Interstitial deletions of 20q are known to occur in polycythemia
      vera and other hematological malignancies, especially those of myeloid origin.

PMID- 11850079
TI  - Involvement of microsatellite instability in lymph node metastasis of endometrial
      carcinoma.
AB  - We evaluated microsatellite instability (MSI) in primary lesions and lymph node
      metastatic lesions in 66 patients with endometrial carcinoma (FIGO stage IIIC)
      accompanied by lymph node metastasis. DNA was extracted from paraffin-embedded
      tissue of both the primary and lymph node metastatic lesions of endometrial
      carcinoma, and MSI was evaluated using microsatellite markers at five loci.
      Microsatellite instability was positive in the primary lesion in 27 patients
      (41%). All patients with MSI-positive primary lesions also showed MSI-positive in
      lymph node metastatic lesions. Of the other 39 patients with MSI-negative primary
      lesions, 4 showed MSI-positive in lymph node metastatic lesions. As the result of
      individual identification by polymerase chain reaction (PCR) using short tandem
      repeat loci in these 4 patients, PCR profiles of primary and metastatic lesions
      matched with those of normal controls in all 4 patients. Therefore, it was
      confirmed that both primary and metastatic lesions developed from the same
      individual. These results suggest that MSI is also involved in lymph node
      metastasis in the development and/or progression of endometrial carcinoma in some
      patients.

PMID- 11850080
TI  - Unrelated clonal chromosome abnormalities in myelodysplastic syndromes and acute
      myeloid leukemias.
AB  - Most neoplasms are monoclonal and the tumor cells are believed to be the progeny
      of a single transformed cell. Clonality has been demonstrated by X-chromosomal
      enzymes, immunoglobulin and T-cell receptor gene rearrangements, or clonal
      cytogenetic abnormalities. Nevertheless, cytogenetically unrelated clones with
      disparate chromosome abnormalities are found infrequently in hematologic
      malignancies. We report four kinds of coexisting independent clones, +8/+21,
      der(1;7)/+8, del(9)/-X/i(Xq), and i(7p)/+11, respectively, which to our knowledge
      mostly have not been reported in same individuals, in two myelodysplastic
      syndrome and two acute myeloid leukemia cases.

PMID- 11850081
TI  - Chronic lymphocytic leukemia with a novel der(8;15)(q10;q10) translocation.
AB  - A 71-year-old male was found to have chronic lymphocytic leukemia. Cytogenetic
      study of the leukemic lymphocytes shows a 46,XY,der(8;15)+15. The der(8;15) is a
      novel chromosomal abnormality in human malignancies. The resulting loss of 8p and
      trisomy 15q are both unusual chromosomal changes in chronic lymphocytic leukemia.

PMID- 11850082
TI  - A new case of acute nonlymphocytic leukemia (French-American-British subtype M1)
      with double minutes and c-MYC amplification.
AB  - Herein, we present a new case of acute nonlymphocytic leukemia (ANLL) French
      American-British M1 subtype with presence of multiple double minutes (dmin)
      derived from the amplification of the c-MYC oncogene. A review of dmins in ANLL
      is presented.

PMID- 11850083
TI  - Comprehensive cytogenetic evaluation of a mature ovarian teratoma case.
AB  - Mature ovarian teratomas are benign ovarian germ cell tumors that usually present
      with a normal karyotype. There are very few reports describing chromosomal
      abnormalities in these tumors, none of which are recurrent. In this study we
      report on a mature teratoma case with clonal chromosomal alterations which
      include monosomies of chromosomes 6, 14, 16, and 21; trisomies of chromosomes 14
      and 21; and deletions of Xq, 5p, 16p, and 17p. Comparative genomic hybridization
      evaluation of the sample revealed a normal profile. These findings are discussed
      together with the cytogenetic reports on other cases of ovarian teratomas
      described in the literature.

PMID- 11850084
TI  - Cytogenetic abnormalities in the lymphocytes of a female patient with primary
      breast carcinoma.

PMID- 11850085
TI  - High performance of the BCR/ABL-extra sensitive (ES) probe for detection of
      der(9q) deletion in t(9;22) (q34;q11.2).

PMID- 11850086
TI  - Sound complexity and 'speechness' effects on pre-attentive auditory
      discrimination in children.
AB  - The evidence in adults suggests that at a cortical level simple and complex
      sounds are processed by partly divergent subsystems. In children, central
      processing of sounds differing in complexity has not been investigated.
      Therefore, the present study examined preconscious discrimination of the
      differences in sound frequency and duration as a function of sound complexity in
      8-10-year-old children. A mismatch negativity (MMN) component of auditory event
      related potentials was elicited in a paradigm where 'deviant' (rare) stimuli were
      either shorter in duration or higher in frequency than the 'standard'
      (repetitive) sounds. Vowels and vowel-matched complex and simple tones were
      presented in separate sequences. The stimulus complexity effects were sizable and
      appeared as larger areas and shorter and more consistent latencies of the MMNs,
      elicited by more complex stimuli. In addition, the vowel frequency MMN showed
      left hemisphere preponderance compared to the complex tone frequency MMN. No such
      effect was found for the duration decrement MMNs. In addition, the complex tone
      duration decrement MMN was distributed posteriorly to either the vowel or
      sinusoidal tone MMNs. A late discriminative negativity, LDN, did not show
      consistent effects of sound complexity. In conclusion, acoustically rich sound
      content facilitates auditory sensory discrimination in 8-10-year-old children.
      The sound 'speechness' effects were not as robust though present. Unlike adults,
      children demonstrated high intersubject variability in discriminating spectrally
      poor, but not rich, sounds. The discrimination of the sound duration appears to
      differ from that of the sound frequency in nature and, consequently, in the
      neural substrates.

PMID- 11850087
TI  - Modification of sudden onset auditory ERP by involuntary attention to visual
      stimuli.
AB  - To investigate the cross-modal nature of the exogenous attention system, we
      studied how involuntary attention in the visual modality affects ERPs elicited by
      sudden onset of events in the auditory modality. Relatively loud auditory white
      noise bursts were presented to subjects with random and long inter-trial
      intervals. The noise bursts were either presented alone, or paired with a visual
      stimulus with a visual to auditory onset asynchrony of 120 ms. In a third
      condition, the visual stimuli were shown alone. All three conditions, auditory
      alone, visual alone, and paired visual/auditory, were randomly inter-mixed and
      presented with equal probabilities. Subjects were instructed to fixate on a point
      in front of them without task instructions concerning either the auditory or
      visual stimuli. ERPs were recorded from 28 scalp sites throughout every
      experimental session. Compared to ERPs in the auditory alone condition, pairing
      the auditory noise bursts with the visual stimulus reduced the amplitude of the
      auditory N100 component at Cz by 40% and the auditory P200/P300 component at Cz
      by 25%. No significant topographical change was observed in the scalp
      distributions of the N100 and P200/P300. Our results suggest that involuntary
      attention to visual stimuli suppresses early sensory (N100) as well as late
      cognitive (P200/P300) processing of sudden auditory events. The activation of the
      exogenous attention system by sudden auditory onset can be modified by
      involuntary visual attention in a cross-model, passive prepulse inhibition
      paradigm.

PMID- 11850088
TI  - Habituation and recovery of a slow negative wave of the event-related brain
      potential.
AB  - This study is concerned with the question of whether the late, slow negative wave
      2 (SNW2) component of the event-related brain potential is a component of the
      orienting response (OR). As habituation of the SNW2 would be an argument for such
      a link with the OR, it was investigated using a variant of the classical
      repetition/change paradigm. Results supported major claims to be made for a
      component of the OR: the amplitude of the vertex SNW2 exhibited roughly the
      typical exponential decline with repeated stimulations (six numeric verbal
      stimuli presented seriatim in an ascending order) and responded incrementally to
      a change, at least in a narrow time slot, i.e. it exhibited partial recovery to
      an out-of-sequence stimulus. These findings were accompanied by similar effects
      on an exemplary OR component, the skin conductance response, and on such possible
      components of the OR as heart rate deceleration and the vertex P3 of the event
      related brain potential. In so far as OR components should behave in comparable
      fashion in response to orienting stimuli, it is thus reasonable to suppose that
      the SNW2 relates to the OR.

PMID- 11850089
TI  - P300 subcomponents and clinical symptoms in schizophrenia.
AB  - A small P300 component of the auditory event-related potential has been found to
      predict poor clinical outcome with a higher amount of thought disorders in
      schizophrenia and has been proposed as a marker for an underlying
      neurodevelopmental disorder with prominent thought disorders, early age of onset,
      prominent negative symptoms and positive family history. The present study was
      designed to confirm our previous findings with subcomponent analysis. Using
      dipole source analysis a temporo-basal (TB) P300 as well as a temporo-superior
      (TS) P300 and LP potential were separated. Fifty patients with schizophrenia (DSM
      IV) were included in the study. Late auditory event-related P300 potentials were
      recorded to infrequent auditory stimuli after treatment psychopathology and
      family history were assessed. The TB-P300 amplitudes were significantly
      negatively correlated with thought disorders remaining after treatment and were
      positively correlated with age of onset. Illness duration was significantly
      correlated to TB-P300 and TS-P300 amplitudes in the group of patients with late
      onset. No significant correlations were found with negative symptoms. Family
      history did not show significant effects on P300. A smaller P300 in patients with
      more thought disorder remaining after stabilization on medication and an earlier
      age of onset support the hypothesis that P300 characterizes schizophrenic
      patients with an underlying neurodevelopmental disorder with specific clinical
      symptom clusters. On the other hand, diminished P300 with illness duration in the
      group of patients with later age of onset supports an underlying
      neurodegenerative progressive process in this subgroup of patients.

PMID- 11850090
TI  - The effects of a caffeine placebo and suggestion on blood pressure, heart rate,
      well-being and cognitive performance.
AB  - We studied the effect of suggestion and different instructions in a balanced
      placebo design. One hundred and fifty-nine subjects were randomized into a 2*4
      factorial design. All subjects except a control group received a caffeine
      placebo. Subjects were randomized to a condition which was identical to an
      earlier study, or received an information about scientifically proven effects of
      caffeine (factor 1). The second factor varied instructions: subjects were either
      made to expect coffee, no coffee or were in a double blind condition and were
      told either coffee or placebo would be applied. Dependent measures were blood
      pressure, heart rate, well-being and a cognitive task. There was one main effect
      of the instruction factor (P=0.03) on diastolic blood pressure, with the group
      'told caffeine' reporting significantly smaller decrease in diastolic blood
      pressure than controls and subjects in the double blind condition. There were no
      other main effects on both the instruction or suggestion factor, and no
      interactions. Contrary to the literature, instruction effects were very small.
      This was apparently due to the fact that placebo-caffeine in the dose used in
      this study--one cup of strong 'coffee'--did not produce expectancy effects strong
      enough to affect the parameters measured. It is concluded that the placebo
      caffeine research paradigm is not suitable for researching instruction effects in
      Germany, and that reported effects should be reproduced with tighter controls.

PMID- 11850091
TI  - The effects of imagery perspective as a function of skill level on alpha
      activity.
AB  - A strategy being used by athletes to enhance their performance is imagery. In
      previous research studying imagery, Lang's (1977, 1979) Information-Processing
      Theory states two types of propositions: stimulus propositions (SP) and response
      propositions (RP). The beneficial use of imagery scripts emphasizing these
      propositions may depend on the skill level of the performer. The purpose of this
      study was to investigate differences in lower (8-10 Hz) and upper (11-13 Hz)
      alpha activities during imagery emphasizing SP and imagery emphasizing RP as
      related to the skill level of the subjects. Twenty-two right-handed male subjects
      were assigned to either an 'expert' (n=11) or a 'novice' (n=11) group. Lower and
      upper alpha activities from six active sites were recorded during imagery of a
      golf-putting task. After subsequent fast Fourier transform (FFT) analysis of
      results, mean lower and upper alpha power values were entered into separate
      repeated measures mixed model designs. Results revealed significant differences
      in skill level at the occipital sites in the lower alpha band. Moreover, a
      significant interaction between imagery perspective and skill level was found in
      the lower alpha band at the occipital site and in the upper alpha band at the
      parietal site. Significant differences were found in imagery perspective at the
      parietal, temporal, and occipital sites in the lower alpha band. In addition, a
      significant interaction effect, imagery perspective by hemisphere, was found in
      the upper alpha band at the parietal site. Conclusions are discussed based on the
      results and future research is suggested.

PMID- 11850092
TI  - Non-linear EEG measures during sleep: effects of the different sleep stages and
      cyclic alternating pattern.
AB  - The objective of this work was to study the non-linear aspects of sleep EEG,
      taking into account the different sleep stages and the peculiar organization of
      its phasic events in ordered sequences (CAP) by applying a series of new non
      linear measures (non-linear cross prediction or NLCP), which appear more reliable
      for the detection and characterization of non-linear structures in experimental
      data than the commonly used correlation dimension. Eight healthy subjects aged 18
      20 years participated in this study. Polysomnography was performed in all
      subjects; signals were sampled at 128 Hz and stored on hard disk. The C3 or C4
      derivation was used for all the subsequent computational steps, which were
      performed on EEG epochs (4096 data points) selected from sleep stage 2 (S2) and
      slow-wave sleep (SWS), in both CAP and non-CAP (NCAP) conditions. Also, epochs
      from sleep stage 1 (S1), REM and wakefulness preceding sleep were recorded. The
      dynamic properties of the EEG were assessed by means of the non-linear cross
      prediction test, which uses three different 'model' time series in order to
      predict non-linearly the original data set (Pred, Ama, and Tir). Pred is a
      measure of the predictability of the time series, and Ama and Tir are measures of
      asymmetry, indicating non-linear structure. The non-linear measures applied in
      this study indicate that sleep EEG tends to show non-linear structure only during
      CAP periods, both during S2 and SWS. Moreover, during CAP periods, non-linearity
      can only be detected during the phase A1 subtypes (and partially A2) of CAP. The
      A3 phases show characteristics of non-stationarity and bear some resemblance to
      wakefulness. Based on the results of this study, sleep might be considered as a
      dynamically evolving sequence of different states of the EEG, which we could
      track by detecting non-linearity, mostly in association with CAP. Our results
      clearly show that detectable non-linearity in the EEG is closely related to the
      occurrence of the phase A of CAP.

PMID- 11850093
TI  - Effect of 1 alpha,25-dihydroxy vitamin D3 and vitamin E on insulin-induced
      glucose uptake in rat adipocytes.
AB  - Vitamin E, an antioxidant, improves insulin sensitivity through the suppression
      of conventional PKC in vascular smooth muscle cells. It has been reported that
      vitamin E reduces platelet aggregation through the suppression of PKC alpha and
      beta (Diabetes 47 (1998) 1494). On the other hand, 1 alpha,25-dihydroxy vitamin
      D3 (1,25D3) activates conventional PKC and may subsequently cause insulin
      resistance. Against this background, we examined the effect of vitamin E and
      1,25D3 on PKC beta and PKC zeta/lambda activities in vitro and 10 nM insulin
      induced glucose uptake in rat adipocytes. In vitro PKC beta activity of
      adipocytes was slightly decreased by the addition of 1 microM vitamin E, but not
      PKC zeta/lambda activity. In contrast, a 10-1000 nM 1,25D3 dose responsively
      activated PKC beta activity of adipocytes (ED 50%, 10 nM), but not PKC
      zeta/lambda activity. Pretreatment with 1 microM vitamin E for 60 min did not
      improve the insulin-induced glucose uptake. On the other hand, pretreatment with
      a 10-1000 nM 1,25D3 dose responsively suppressed insulin-induced glucose uptake.
      Moreover, 1,25D3 increased membrane-associated PKC beta immunoreactivity for 60
      min, but no additional increase in membrane-associated PKC beta immunoreactivity
      during treatment with insulin was observed. These results suggest that 1,25D3
      reduces insulin-induced glucose uptake via activation of PKC beta, but not
      vitamin E in rat adipocytes.

PMID- 11850094
TI  - Total homocysteine and cognitive deterioration in people with type 2 diabetes.
AB  - The aim of this study was to investigate the relationship between total
      homocysteine levels in people with Type 2 diabetes and cognitive status. Fifty
      patients from our diabetes unit (30 females/20 males) with diabetes were
      enrolled. All patients had fasting blood samples taken for measurement of
      cardiovascular risk factors; total cholesterol and triglyceride concentrations
      and other lipid fractions (lipoprotein (a), low density lipoprotein (LDL
      cholesterol), high density lipoprotein (HDL-cholesterol)), glucose, HbA(1c) and
      homocysteine. 24-h urine collection was used to measure creatinine clearance and
      microalbuminuria. Vitamin B-12 and folate were measured to assess vitamin status.
      All diabetic patients were assessed for late complications and a Mini-Mental
      State Examination (MMSE) was performed. The patients were 64.6 (49-78) years old
      with body mass index (BMI) of 29.6 +/- 6.3 kg/m(2), and duration of diabetes of
      8.9 +/- 6.7 years. A univariant correlation analysis was performed among
      cardiovascular risk factors and vitamins with total MMSE score. Total
      homocysteine was inverse by correlated with MMSE score (r=-0.38; P<0.05) of the
      other measures of cardiovascular risk, microalbuminuria showed an inverse
      correlation with MMSE score (r=-0.51:P<0.01). Lipoproteins, glucose control and
      vitamin status were not correlated MMSE score. In the multiple regression model
      only microalbuminuria remained in the model, showing a decrease of one point in
      the MMSE result with each milligram of microalbuminuria, adjusted for confounding
      factors. Cognitive status in type 2 diabetic was correlated with homocysteine
      levels and microalbuminuria, this last endothelial damage marker remaining as an
      independent risk factor of cognitive deterioration.

PMID- 11850095
TI  - Pedometer-determined ambulatory activity in individuals with type 2 diabetes.
AB  - This cross-sectional study presents the first normative data on pedometer
      determined ambulatory activity, defined as steps/day, in 160 (98 males, 62
      females; age=52.4 +/- 5.3 years; BMI=32.3 +/- 5.7) free-living individuals with
      type 2 diabetes. Participants took 6662 +/- 3077 steps per day, less than that
      reported in nondiabetic samples and more than that reported for samples living
      with more restrictive chronic conditions including claudication, joint
      replacement, chronic obstructive lung disease, and chronic heart failure.
      Steps/day and BMI were inversely and significantly correlated (r=-0.27, P<0.01).
      Further, there was a significant difference between BMI categories (from normal
      weight to obesity class III) with regard to steps/day (F=2.96, P<0.05). The
      difference was most apparent between the highest obesity classes (II and III) and
      normal weight categories. This data is useful for sample comparison purposes. In
      addition the standard deviation or variance estimates can be used to calculate
      samples sizes for intervention efforts. Objective quantification of ambulatory
      activity via simple and inexpensive pedometers permits researchers and
      practitioners to easily screen for level of activity along a continuum. This
      study opens the door for future research and clinical applications including
      identifying threshold values related to important health outcomes and evaluating
      incremental change due to various interventions in this population.

PMID- 11850096
TI  - Insulin improves well-being for selected elderly type 2 diabetic subjects.
AB  - The effects of insulin therapy on patient well-being, treatment satisfaction and
      mood, and on carer strain were studied in 30 elderly Type 2 diabetic patients
      (age 73 +/- 7 (SD) yr) in poor glycaemic control on tablet therapy. A comparison
      group of ten poorly controlled patients who remained on oral agents was also
      studied. After 4 weeks of insulin treatment, there were significant improvements
      in mental health, role-emotional, role-physical (all P<0.05) and vitality
      (P<0.01) domains of the short form health survey (SF-36), and also in the
      diabetes treatment and satisfaction questionnaire (DTSQ) and geriatric depression
      scale (both P<0.01) compared to baseline. After 12 weeks, the improvements in
      mental health, social functioning and vitality (P<0.01 for all domains), and in
      the DTSQ were sustained. Carer strain was lower at 4 weeks. No changes in
      outcomes were seen in the comparison group. In selected elderly Type 2 diabetic
      patients, insulin treatment is associated with significant improvements in well
      being, treatment satisfaction and mood, even without significant improvements in
      glycaemic control and without increase in carer strain. The SF-36 and DTSQ are
      sensitive to the benefits of the changes in the treatment for these patients.

PMID- 11850097
TI  - The effectiveness of hydroxychloroquine in patients with type 2 diabetes mellitus
      who are refractory to sulfonylureas--a randomized trial.
AB  - AIM: To assess the glucose-lowering efficacy, responsiveness, duration of action
      and impact on quality-of-life of hydroxychloroquine (HXCHL), when added as an
      antihyperglycemic agent to patients with sulfonylurea-refractory type 2 diabetes.
      METHODS: One hundred and thirty-five obese patients with type 2 diabetes (mean
      age 57.5 years) and a glycated hemoglobin (GHb) > or = 11% despite maximum
      sulfonylureas were randomly allocated to the addition of HXCHL (up to 300 mg bid)
      or placebo and followed for up to 18 months. Randomization was stratified by
      baseline GHb (<13.5% versus > or = 13.5%). The primary outcome was 'blinded'
      withdrawal of study drug due to unacceptable glycemic control; GHb, glucose
      tolerance, lipids, and quality of life were also assessed. RESULTS: Those on
      placebo were more likely to be withdrawn from study drug because of unacceptable
      glycemic control than patients randomized to HXCHL (95.5 and 69.6% given placebo
      and HXCHL, respectively; P=0.0001). During the first 6 months, HXCHL decreased
      GHb by an absolute amount of 1.02% more than placebo (95% CI 0.24, 1.81). Glucose
      tolerance and LDL cholesterol improved during the first 3 months of therapy. No
      significant adverse effects were noted. Factors that predicted responsiveness
      included an initial GHb <13.5%, early responsiveness to study drug, and no prior
      metformin use. Lower GHb levels at baseline predicted a better response; the
      hazard of withdrawal increased 36% (95% CI 11%, 66%) for every 1% increase in GHb
      even in patients whose baseline GHb was <13.5%. CONCLUSIONS: HXCHL improves
      glycemic control in sulfonylurea-refractory patients with poorly controlled type
      2 diabetes.

PMID- 11850098
TI  - Different effects of acarbose and glibenclamide on proinsulin and insulin
      profiles in people with Type 2 diabetes.
AB  - AIM: In a double-blind, placebo-controlled study, we compared the effect of
      acarbose (A) and glibenclamide (G) on post-prandial (pp) and 24-h profiles of
      proinsulin and insulin. METHODS: Twenty-seven patients with Type 2 diabetes
      mellitus insufficiently controlled with diet alone were randomised to receive
      acarbose, 100 mg thrice daily, glibenclamide, 1 mg thrice daily, or placebo.
      Before and after 16 weeks of treatment, 24-h profiles of proinsulin, insulin and
      glucose (fasting, 1 h after breakfast and every 3-h for a 24-h period) were
      measured under metabolic ward conditions with standardised meals. RESULTS: With
      acarbose, a reduced 24-h level of proinsulin was observed compared with
      glibenclamide (AUC 1096 +/- 118 vs. 1604 +/- 174 pmol/l per h, P<0.05) at 16
      weeks. The breakfast increment of proinsulin was lower with acarbose than
      glibenclamide (6.8 vs. 19.3 pmol/l, P<0.05) as was the level at that time (37.3
      +/- 5.3 vs. 56.4 +/- 7.5 pmol/l, P<0.05). A lower AUC of insulin after treatment
      was also observed with acarbose than glibenclamide (7.9 +/- 0.9 vs. 14.8 +/- 4.5
      nmol/l per h, P<0.05), as also for 1-h increment (81 +/- 26, vs. 380 +/- 120
      pmol/l, P<0.01) and 1-h level (325 +/- 30 vs. 621 +/- 132 pmol/l, P<0.01).
      Acarbose reduced 1-h breakfast glucose increment (baseline 6.3 +/- 0.6, 16-week
      3.5 +/- 0.6 mmol/l, P<0.01) and 1-h glucose level (18.1 +/- 1.1 and 14.5 +/- 1.3
      mmol/l, P<0.01), whereas glibenclamide did not (6.6 +/- 0.7 vs. 5.4 +/- 0.6
      mmol/l and 18.9 +/- 1.5 vs. 15.3 +/- 1.3 mmol/l). CONCLUSIONS: Measurement of
      circadian excursions of proinsulin and insulin reveals distinct differences in
      meal-time proinsulin and insulin increment and level between acarbose and
      glibenclamide whereas fasting levels of these insulin fractions remained
      unaffected.

PMID- 11850100
TI  - Cell-mediated immune responses to GAD and beta-casein in type 1 diabetes mellitus
      in Thailand.
AB  - We measured the cell-mediated immune response to GAD and bovine beta-casein in 38
      type 1 and 37 type 2 diabetic patients who visited diabetic clinics or who were
      hospitalized in Bangkok, Thailand, and in 43 normal controls, by using a
      lymphoproliferation assay. Positive results against GAD were found in 29/38
      (76.3%) type 1, 6/37 (16.2%) type 2 diabetic patients and 1/43 (2.3%) normal
      controls. Positive results against bovine beta-casein were found in 18/38
      (47.4%), 5/37 (13.5%) and 1/43 (2.3%) of these subjects, respectively. The
      frequencies of the positive results and the magnitude of the responses to both
      antigens in type 1 diabetic patients were significantly higher than those in the
      other two groups (P<0.001). In addition, the prevalence of a positive
      lymphoproliferative response to these antigens in type 1 diabetic patients was
      higher than that of anti-GAD antibody positivity in the same group of subjects
      (26.3%). Thus, the prevalence of positive lymphoproliferative response to GAD in
      type 1 diabetic patients studied was higher than the prevalence of other
      autoimmune markers previously reported in type 1 diabetic patients in Thailand.

PMID- 11850099
TI  - Validation of simple indices to assess insulin sensitivity based on the oral
      glucose tolerance test in the Japanese population.
AB  - The homeostasis model assessment (HOMA) represents a simple index for evaluating
      insulin sensitivity, but clinical use is limited. Insulin sensitivity indices
      calculated from plasma glucose and plasma insulin concentrations after an oral
      glucose tolerant test (OGTT) have been proposed, but have not been validated in
      the Japanese population. We compared these indices with the euglycemic
      hyperinsulinemic clamp technique to evaluate the predicting insulin sensitivities
      in 77 Japanese subjects with varying degrees of glucose tolerance (normal glucose
      tolerance, n=40; impaired glucose tolerance, n=22; and type 2 diabetes mellitus,
      n=15). Insulin sensitivity was measured by the euglycemic hyperinsulinemic
      glucose clamp technique using an artificial pancreas, and expressed as the M
      value. Weak inverse correlations existed between the HOMA index and M-values (r=
      0.227, P=0.0468). An alternative index calculated by Matsuda's formula correlated
      with the M-value (r=0.450, P=0.0001). A second index calculated by Stumvoll's
      formula also correlated with the M-value (r=0.641, P=0.0001). Finally, a third
      index calculated by Gutt's formula also significantly correlated with the M-value
      (r=0.526, P=0.0001). All three indices are applicable for clinical use. The
      second index is the most sensitive measure of insulin sensitivity in the Japanese
      population.

PMID- 11850101
TI  - Severity at onset of childhood type 1 diabetes in countries with high and low
      incidence of the condition.
AB  - Severity of Type 1 diabetes mellitus (DM) at presentation was compared between
      south-east Sweden and Lithuania where incidence of childhood Type 1 diabetes is
      three times lower than in Sweden. New cases of diabetes at age 0-15 years from
      August 1995 to March 1999 in south-east Sweden and from August 1996 to August
      2000 in Lithuania were included. Symptoms and clinical characteristics at
      diagnosis were recorded. Data about the close environment were collected using
      questionnaires. Lithuanian children were diagnosed in a more severe condition,
      mean pH 7.30 and HbA(1c) 11.5% compared with mean pH 7.36 and HbA(1c) 9.7% in
      Swedish children (P<0.0001). More Lithuanian than Swedish children were diagnosed
      in ketoacidosis (pH < or = 7.2, hyperglycaemia and ketonuria), 21.3 versus 7.3%
      (P<0.0001). Only 4.6% of Swedish children and 1.0% of Lithuanian children had no
      symptoms (P=0.007). Children in families with at least one first degree relative
      with diabetes (12.2% in Sweden and 8.4% in Lithuania, NS) had laboratory values
      at diagnosis closer to normal than sporadic cases in either country. Factors
      predicting ketoacidosis in Sweden were an unemployed mother and absence of
      infections in the 6 months before diagnosis. In Lithuania it was younger age and
      mother with less education. Additional educational activities for doctors are
      needed in countries with low incidence to reduce prevalence of ketoacidosis at
      onset.

PMID- 11850103
TI  - Impairment of brain mitochondrial function by reactive nitrogen species: the role
      of glutathione in dictating susceptibility.
AB  - Mitochondrial enzymes involved in energy metabolism display varying degrees of
      sensitivity towards reactive nitrogen species such as peroxynitrite (ONOO-). With
      regards to the electron transport chain, cytochrome oxidase appears particularly
      sensitive. Inhibition of this component may lead to an increase in mitochondrial
      superoxide formation, exacerbation of cellular oxidative stress and further
      mitochondrial damage. Impairment of the electron transport chain may lead to a
      loss of membrane potential, ATP deficiency, opening of the permeability
      transition pore and the release of factors capable of initiating apoptosis.
      Reduced glutathione will react, via a number of diverse reactions, with reactive
      nitrogen species and hence is capable of limiting mitochondiral damage. Loss of
      brain glutathione may therefore be an important factor in those neurological
      conditions in which there is evidence of excessive nitric oxide formation and
      mitochondrial damage.

PMID- 11850104
TI  - Peripheral benzodiazepine receptors and mitochondrial function.
AB  - For over 20 years, numerous investigations have focused on elucidating the
      function of the peripheral benzodiazepine receptor (PBR). This relatively small
      protein (18kDa) arouses great interest because of its association with numerous
      biological functions, including the regulation of cellular proliferation,
      immunomodulation, porphyrin transport and heme biosynthesis, anion transport,
      regulation of steroidogenesis and apoptosis. Although the receptor was first
      identified as a binding site for the benzodiazepine, diazepam, in peripheral
      organ systems, the PBR was subsequently found to be distinct from the central
      benzodiazepine receptor (CBR) in terms of its pharmacological profile, structure,
      subcellular localization, tissue distribution and physiological functions. The
      PBR is widely expressed throughout the body, with high densities found in steroid
      producing tissues. In contrast, its expression in the CNS is restricted to
      ependymal cells and glia. The benzodiazepine Ro5-4864 and the isoquinoline
      carboxamide PK11195 exhibit nanomolar affinity for the PBR, and are the archtypic
      pharmacological tools for characterizing the receptor and its function. Primary
      among these functions are its regulation of steroidogenesis and apoptosis, which
      reflect its mitochondrial localization and involvement in oxidative processes.
      This review will evaluate the basic pharmacology and molecular biology of the
      PBR, and highlight its role in regulating mitochondrial function, the
      mitochondrial transmembrane potential and its sensitivity to reactive oxygen
      species (ROS), and neurosteroid synthesis, processes relevant to the pathogenesis
      of a number of neurological and neuropsychiatric disorders.

PMID- 11850105
TI  - Mitochondrial dysfunction in acute hyperammonemia.
AB  - Acute hyperammonemia resulting from congenital urea cycle disorders, Reye
      syndrome or acute liver failure results in severe neuronal dysfunction, seizures
      and death. Increasing evidence suggests that acute hyperammonemia results in
      alterations of mitochondrial and cellular energy function resulting from ammonia
      induced inhibition of the tricarboxylic acid cycle enzyme alpha-ketoglutarate
      dehydrogenase and by activation of the NMDA receptor. Antagonists of this
      receptor and NOS inhibitors prevent acute ammonia-induced seizures and mortality
      and prevent acute ammonia-induced changes in mitochondrial calcium homeostasis
      and cellular energy metabolism. Acute hyperammonemia also results in decreased
      activities of free radical scavenging enzymes and again, free radical formation
      due to ammonia exposure is prevented by either NMDA receptor antagonists or NOS
      inhibitors. Acute hyperammonemia also results in activation of "peripheral-type"
      benzodiazepine receptors and monoamine oxidase-B, enzymes which are localized on
      the mitochondrial membranes of astrocytes in the CNS. Activation of these
      receptors results in mitochondrial swelling and in increased degradation of
      monoamines, respectively. Alterations of mitochondrial function could contribute
      to the neuronal dysfunction characteristic of acute hyperammonemic syndromes.

PMID- 11850106
TI  - Interactions of oxidative stress with thiamine homeostasis promote
      neurodegeneration.
AB  - Thiamine-dependent processes are diminished in brains of patients with several
      neurodegenerative diseases. The decline in thiamine-dependent enzymes can be
      readily linked to the symptoms and pathology of the disorders. Why the reductions
      in thiamine linked processes occur is an important experimental and clinical
      question. Oxidative stress (i.e. abnormal metabolism of free radicals)
      accompanies neurodegeneration and causes abnormalities in thiamine-dependent
      processes. The vulnerability of thiamine homeostasis to oxidative stress may
      explain deficits in thiamine homeostasis in numerous neurological disorders. The
      interactions of thiamine with oxidative processes may be part of a spiral of
      events that lead to neurodegeneration, because reductions in thiamine and
      thiamine-dependent processes promote neurodegeneration and cause oxidative
      stress. The reversal of the effects of thiamine deficiency by antioxidants, and
      amelioration of other forms of oxidative stress by thiamine, suggest that
      thiamine may act as a site-directed antioxidant. The data indicate that the
      interactions of thiamine-dependent processes with oxidative stress are critical
      in neurodegenerative processes.

PMID- 11850107
TI  - Neurolathyrism: mitochondrial dysfunction in excitotoxicity mediated by L-beta
      oxalyl aminoalanine.
AB  - beta-N-Oxalyl amino-L-alanine (L-BOAA); synonym beta-N-oxalyl-alpha,beta
      diaminopropionic acid (beta-ODAP) is a naturally occurring non-protein amino acid
      present in the chickling pea from the plant Lathyrus sativus grown in drought
      prone areas. Ingestion of L-BOAA as a staple diet results in a progressive
      neurodegenerative condition, neurolathyrism, a form of motor neuron disease which
      affects the upper motor neurons and anterior horn cells of the lumbar spinal
      cord. L-BOAA is an excitatory acid and acts as an agonist at the AMPA receptor.
      One of the primary effects of L-BOAA toxicity is the inhibition of mitochondrial
      complex I selectively in the motor cortex and lumbar spinal cord. Recent evidence
      has suggested that the mitochondrial dysfunction is a consequence of oxidation
      protein thiol groups as a result of generation of reactive oxygen species.
      Mitochondrial complex I is highly to vulnerable to inactivation through oxidation
      of vital sulfhydryl groups. Thiol antioxidants such as alpha-liopic acid offer a
      method of protecting mitochondrial function. A common mechanism involving
      oxidation of protein thiol groups may underlie neurodegeneration occurring
      through mitochondrial dysfunction induced by excitatory amino acid.

PMID- 11850108
TI  - Mitochondrial contributions to tissue damage in stroke.
AB  - Tissue infarction, involving death of essentially all cells within a part of the
      brain, is a common pathology resulting from stroke and an important determinant
      of the long-term consequences of this disorder. The cell death that leads to
      infarct formation is likely to be the result of multiple interacting pathological
      processes. A range of factors, including the severity of the ischemic insult and
      whether this is permanent or reversed, determine which mechanisms predominate.
      Although evaluating mitochondrial properties in intact brain is difficult,
      evidence for several potentially deleterious responses to cerebral ischemia or
      post-ischemic reperfusion have been obtained from investigations using animal
      models of stroke. Marked changes in ATP and related energy metabolites develop
      quickly in response to occlusion of a cerebral artery, as expected from
      limitations in the delivery of oxygen and glucose. However, these alterations are
      often only partially reversed on reperfusion despite improved substrate delivery.
      Ischemia-induced decreases in the mitochondrial capacity for respiratory activity
      probably contribute to the ongoing impairment of energy metabolism during
      reperfusion and possibly also to the magnitude of changes seen during ischemia.
      Conditions during reperfusion are likely to be conducive to the induction of the
      permeability transition in mitochondria. There are as yet no well-characterized
      techniques to identify this change in the intact brain. However, the protective
      effects of some agents that block formation of the transition pore are consistent
      with both the induction of the permeability transition during early recirculation
      and a role for this in the development of tissue damage. Release of cytochrome c
      into the cytoplasm of cells has been observed with both permanent and reversed
      ischemia and could trigger the death of some cells by apoptosis, a process which
      probably contributes to the expansion of the ischemic lesion. Mitochondria are
      also likely to contribute to the widely-accepted role of nitric oxide in the
      development of ischemic damage. These organelles are a probable target for the
      deleterious effects of this substance and can also act as a source of superoxide
      for reaction with the nitric oxide to produce the damaging species,
      peroxynitrite. Further characterization of these mitochondrial responses should
      help to elucidate the mechanisms of cell death due to cerebral ischemia and
      possibly point to novel sites for therapeutic interventions in stroke.

PMID- 11850109
TI  - Amyloid-beta, tau alterations and mitochondrial dysfunction in Alzheimer disease:
      the chickens or the eggs?
AB  - Alzheimer disease (AD) is defined pathologically and diagnostically defined by
      amyloid-beta senile plaques and neurofibrillary tangles (NFT) composed of tau.
      From the time of their original description nearly a century ago, a major focus
      has been to understand the role that these lesions play in the pathogenesis of
      the disease. The majority favors the notion that these lesions cause the disease
      and therefore attempts at therapeutic intervention are focused on preventing
      lesions formation. However, this rationale may be misguided since new evidence
      from our laboratories and others suggest that the lesions not only occur as a by
      product of the fundamental disease process but also that they may be protective.

PMID- 11850110
TI  - Mitochondrial involvement in Parkinson's disease.

PMID- 11850111
TI  - Mitochondrial involvement in amyotrophic lateral sclerosis.
AB  - The causes of motor neuron death in amyotrophic lateral sclerosis (ALS) are so
      far unknown. The involvement of mitochondria in the disease was initially
      suggested by ultrastructural studies. More recently these observations have been
      supported by studies of mitochondrial function in ALS. Alterations in the
      activity of complexes which make up the mitochondrial electron transport chain
      have been recorded as well as mutations in the mitochondrial genome. The calcium
      buffering function of the mitochondria may also be affected in the disease. This
      review will discuss how mitochondrial dysfunction could be of relevance in ALS
      and the evidence that an alteration of mitochondrial function is a feature of the
      disease. The way in which the involvement of mitochondria fits with other
      aetiological hypotheses for ALS will also be discussed.

PMID- 11850112
TI  - Spinocerebellar ataxias due to mitochondrial defects.
AB  - A number of ataxias have been shown to result from defects in mitochondrial
      function. The genes responsible for Friedreich ataxia (FRDA) and for X-linked
      sideroblastic anemia with ataxia are nuclear genes that encode mitochondrial
      proteins. These genes, which are highly conserved in species as diverse as humans
      and yeast, play a role in mitochondrial iron metabolism and in the formation of
      iron-sulfur clusters. Defects in vitamin E metabolism, due to mutations in
      tocopherol transfer protein (TTP), also result in ataxia. It is hypothesized that
      the biochemical feature common to these ataxias is increased oxidant damage
      either through increased oxidants or decreased anti-oxidants.

PMID- 11850113
TI  - Mitochondrial dysfunction in progressive supranuclear palsy.
AB  - A progressive impairment of mitochondrial function has been suggested to play a
      critical role in the pathogenesis of several neurodegenerative diseases,
      including Parkinson's disease, Alzheimer's disease and Huntington's disease.
      Mitochondrial dysfunction can lead to number of deleterious consequences
      including impaired calcium buffering, generation of free radicals, activation of
      the mitochondrial permeability transition pore and secondary excitotoxicity.
      Progressive supranuclear palsy (PSP) is a rare neurological disorder
      characterized by the appearance of supranuclear gaze palsy and extrapyramidal
      symptoms [Arch. Neurol. 10 (1964) 333]. Although the etiological basis of PSP is
      unknown, compelling evidence from spectroscopy studies in PSP patients,
      biochemical studies in post-mortem PSP brain tissue and PSP cybrids has emerged
      that supports a contributory role of bio-energetic defects in the pathogenesis of
      PSP.

PMID- 11850114
TI  - Mitochondrial dysfunction in the neuronal ceroid-lipofuscinoses (Batten disease).
AB  - There are at least eight genetic entities known as the ceroid-lipofuscinoses in
      humans which share clinical and pathological features that have caused them to be
      grouped together under the eponym of Batten disease. They present pathologically
      as lysosomal storage diseases but are also characterised by severe
      neurodegeneration. Although the biochemical defects appear primarily centred on
      lysosomes and defects in proteolysis, the link between this and pathogenesis of
      neuronal death is poorly understood. The pathogenesis of neurodegeneration has
      been studied particularly in two animal models these being the English setter dog
      and the New Zealand Southhampshire sheep (OCL6). In these, and some of the human
      entities, there is evidence of mitochondrial dysfunction. This includes the
      accumulation of subunit c of ATP synthase as a component of storage material in
      at least six of eight genetic forms of the disease; structural abnormalities of
      mitochondria and selective loss of neurons in areas of the brain that are
      particularly metabolically active. Direct evidence of dysfunction comes from
      mitochondrial function tests in fibroblasts and, in animal models, isolated liver
      mitochondria. Supporting evidence of mitochondrial dysfunction was shown by
      disturbances in proportions of energy-rich phosphates in fibroblasts in some of
      these diseases. If these various defects were reflected in neurons, then it would
      support the hypothesis that neuron death was associated with energy-linked
      excitotoxicity.

PMID- 11850116
TI  - Age-related phenotypes in the staggerer mouse expand the RORalpha nuclear
      receptor's role beyond the cerebellum.
AB  - The homozygous mutant mouse staggerer (RORa(sg)/RORa(sg)), was initially
      described as ataxic, due to the presence of massive neurodegeneration in the
      cerebellum [Science 136 (1962) 610]. The identification of the widely expressed
      Retinoic acid receptor-related Orphan Receptor, NR1F1 (RORalpha) gene as the site
      of mutation in the staggerer mouse has led to great progress in understanding the
      molecular basis of its phenotype in recent years [Nature 379 (1996) 736].
      RORalpha is a transcription factor, belonging to the nuclear receptor
      superfamily, for which no natural ligand has yet been identified. Mice engineered
      for the disruption of the gene encoding RORalpha display the same cerebellar
      atrophic phenotype as the staggerer mouse [Proc. Natl. Acad. Sci. USA 95 (1998)
      3960]. More recently, it has been shown that the mutation is semi-dominant, as
      heterozygous animals display an increased loss of Purkinje cells with age.
      Furthermore, a number of additional phenotypes outside the nervous system have
      recently been identified. These include a greater susceptibility to
      atherosclerosis [Circulation 15 (1998) 2738], immunodeficiencies linked to the
      overexpression of inflammatory cytokines [J. Neurochem. 58 (1992) 192],
      abnormalities in the formation and maintenance of bone tissue [Proc. Natl. Acad.
      Sci. USA 97 (2000) 9197] and changes in muscle differentiation [Nucleic Acids
      Res. 27 (1999) 411]. Thus, RORalpha has been directly linked to a number of age
      related pathologies of great medical interest.

PMID- 11850115
TI  - Optic nerve degeneration and mitochondrial dysfunction: genetic and acquired
      optic neuropathies.
AB  - Selective degeneration of the smallest fibers (papillo-macular bundle) of the
      human optic nerve occurs in a large number of optic neuropathies characterized
      primarily by loss of central vision. The pathophysiology that underlies this
      peculiar pattern of cell involvement probably reflects different forms of genetic
      and acquired mitochondrial dysfunction. Maternally inherited Leber's hereditary
      optic neuropathy (LHON), dominant optic atrophy (Kjer disease), the optic atrophy
      of Leigh's syndrome, Friedreich ataxia and a variety of other conditions are
      examples of inherited mitochondrial disorders with different etiologies. Tobacco
      alcohol amblyopia (TAA), the Cuban epidemic of optic neuropathy (CEON) and other
      dietary (Vitamins B, folate deficiencies) optic neuropathies, as well as toxic
      optic neuropathies such as due to chloramphenicol, ethambutol, or more rarely to
      carbon monoxide, methanol and cyanide are probably all related forms of acquired
      mitochondrial dysfunction. Biochemical and cellular studies in LHON point to a
      partial defect of respiratory chain function that may generate either an ATP
      synthesis defect and/or a chronic increase of oxidative stress. Histopathological
      studies in LHON cases and a rat model mimicking CEON revealed a selective loss of
      retinal ganglion cells (RGCs) and the corresponding axons, particularly in the
      temporal-central part of the optic nerve. Anatomical peculiarities of optic nerve
      axons, such as the asymmetric pattern of myelination, may have functional
      implications on energy dependence and distribution of mitochondrial populations
      in the different sections of the nerve. Histological evidence suggests impaired
      axonal transport of mitochondria in LHON and in the CEON-like rat model,
      indicating a possible common pathophysiology for this category of optic
      neuropathies. Histological evidence of myelin pathology in LHON also suggests a
      role for oxidative stress, possibly affecting the oligodendrocytes of the optic
      nerves.

PMID- 11850117
TI  - Insulin receptor tyrosine kinase activity and phosphorylation of tyrosines 1162
      and 1163 are required for insulin-increased prolactin gene expression.
AB  - Insulin treatment increased prolactin gene expression in GH4 cells, a rat
      pituitary tumor cell line, through the endogenous insulin receptor. However,
      insulin regulation of transfected plasmids required the expression of
      cotransfected insulin receptor. Prolactin-CAT expression was increased 12-fold in
      cells transfected with wild type insulin receptor, but insulin did not increase
      prolactin gene expression when a kinase negative mutant of the ATP binding site
      (K1030R) was expressed. Thus, receptor kinase activity was required for signaling
      to gene transcription. Mutation of tyrosine 1158 did not reduce insulin-increased
      prolactin-CAT expression while individual mutations of tyrosine 1162 and tyrosine
      1163 each reduced insulin-increased prolactin-CAT expression by 50% and a triple
      mutant of tyrosines 1158/1162/1163 was inactive. Thus, mutation of tyrosine 1162
      and 1163 was also sufficient to inactivate signaling by the insulin receptor.
      Insulin-stimulated auto phosphorylation occurred in all mutants in vitro except
      the ATP binding site mutant. However, the ability of mutant insulin receptors to
      mediate insulin-increased prolactin-CAT expression correlated with the substrate
      specific catalytic activity of the receptors. This suggested that phosphorylation
      of these tyrosines was important for substrate access to the catalytic domain of
      the receptor.

PMID- 11850118
TI  - The vasopressin gene non-canonical Hogness box: effect on protein binding and
      promoter function.
AB  - Comparison of the promoter sequences of the genes encoding the neuropeptide
      hormone vasopressin from a number of organisms has revealed that they do not
      contain a classical Hogness box. In all vertebrate species examined, the
      canonical TATA box is replaced with a CATA sequence. We hypothesised that this
      conserved modified sequence may play a role in the regulation of vasopressin
      promoter activity. We used electrophoretic mobility shift assays to show that
      TATA and CATA sequences generate different complexes with SON nuclear proteins.
      Further, the transfection of wild-type (CATA) and mutated (TATA) VP promoter
      reporter constructs into a heterologous cell line demonstrated a sequence
      specific effect on transcriptional activity. The CATA sequence contributes to
      weaker promoter activity than a TATA box, but is able to interact with the
      upstream elements to increase the efficacy of an enhancer. The CATA box may thus
      be involved in the cell-specific and physiological regulation of the VP gene.

PMID- 11850120
TI  - Interleukin-1 is a potent growth factor for immature rat sertoli cells.
AB  - Testes from rats of different maturational ages were explored for presence of
      paracrine sertoli cell growth factors. Pubertal and adult testes contained a 17
      kDa protein, with potent stimulatory effect on immature Sertoli cell
      multiplication in vitro. The bioactivity of this protein was mimicked by rat
      interleukin-1 (IL-1) and neutralized by IL-1 receptor antagonist. A receptor
      mediated action was further supported by the demonstration of IL-1 receptor type
      I mRNA and protein expression in the cultured sertoli cells and in intact
      immature rat testes. IL-1alpha showed higher efficacy in stimulating
      proliferation than IL-1beta and follicle-stimulating hormone (FSH), and displayed
      synergistic action in combination with FSH. As IL-1alpha is constitutively
      produced by the rat testis and IL-1beta readily inducible by proinflammatory
      stimuli, our results suggest that IL-1 may serve as a growth factor for Sertoli
      cells under physiological and pathophysiological conditions.

PMID- 11850119
TI  - Characterization and primary structures of bovine and porcine thyroxine-binding
      globulin.
AB  - Thyroxine-binding globulin (TBG) is the major serum transport protein for
      iodothyronines in most of the large, omni- or herbivorous mammals.
      Characterization of human TBG (hTBG), including its 20 known natural variants,
      allowed the identification of the ligand-binding site and a correlation of
      diminished synthesis or loss of function with mutations in the TBG gene. Further
      refinement of the structure-function correlation, especially the high binding
      affinity and heat stability, requires characterization of other mammalian TBGs,
      of which only rat and sheep TBG were available. We now present some of the
      chemical and physical properties of bovine TBG (bTBG) and porcine TBG (pTBG) and
      their primary structures deduced from their cDNA sequences. The serum
      concentrations of bTBG and pTBG estimated by Scatchard analysis of T(4)-binding
      were similar to hTBG. The T(4)-binding affinity of human, bovine and porcine TBGs
      were all similar, at 1.2x10(10) M(-1). However, heat stability of the animal TBGs
      was reduced, with a half life of denaturation of 7 min (bTBG) and 5 min (pTBG) at
      55 degreeC, compared with 21 min for hTBG. Nucleotide alignment revealed identity
      with hTBG of 85.5% (bTBG) and 83.7% (pTBG) and amino acid identity of 82.8%
      (bTBG) and 82.6% (pTBG). As expected, the relevant parts of the ligand-binding
      domain (amino acids 215-291, and 363-395) were highly conserved at more than 95%
      similarity. Comparison of the five known mammalian TBGs allows focusing of future
      mutagenesis experiments to further characterize the properties of the molecule.

PMID- 11850121
TI  - Thyroid hormone exerts site-specific effects on SRC-1 and NCoR expression
      selectively in the neonatal rat brain.
AB  - Thyroid hormone receptors (TRs) are ligand-gated transcription factors. Recently,
      many coregulator proteins have been identified that interact with steroid/TRs and
      are required for the activation or repression of hormone sensitive genes. We
      tested whether steroid receptor coactivator-1 (SRC-1) and nuclear corepressor (N
      CoR) expression is altered by hypothyroidism in rat brains on gestational day 16
      and postnatal day 15. We found that both SRC-1 and N-CoR mRNA levels were
      decreased in the cortex and dentate gyrus of 6-n-propyl-2 thiouracil treated rats
      only on P15, while mRNA levels for both genes were increased in the same CA3
      region of the brains. These findings do not support the idea that cofactors are
      involved in the compensatory mechanisms for conserving TH action, but they do
      suggest that hypothyroidism affects the responsiveness of tissues to steroid
      hormones by altering the expression of necessary cofactors.

PMID- 11850122
TI  - Steroid hormonal regulation of proliferative, p53 tumor suppressor, and apoptotic
      responses of sheep ovarian surface epithelial cells.
AB  - Ovarian surface epithelial cells have been implicated in the genesis of common
      ovarian cancers. The integrity of DNA of ovarian surface epithelial cells
      contiguous with the ovulatory stigma becomes compromised during the rupture
      process; most cells degenerate by apoptosis, however some, bearing sublethal
      lesions, persist along the margins of ovulated follicles. Clonal expansion of a
      genetically-damaged surface epithelial cell (i.e. with unrepaired DNA, but not
      committed to death) can presumably give rise to ovarian carcinoma. It was
      hypothesized that estradiol and progesterone regulate ovarian surface epithelial
      cell-cycle dynamics associated with folliculo-luteal transitions and ovulatory
      wound repair/remodeling. Progesterone up-regulated the tumor suppressor p53 and
      inhibited baseline and estradiol-stimulated proliferation of cultured sheep
      ovarian surface epithelial cells. Anti/mitotic responses to steroid hormones were
      transcriptionally- and receptor-dependent. Rates of apoptosis (DNA fragmentation)
      were unaffected by progesterone. High concentrations of estradiol, via a
      nongenomic (perhaps antioxidant) mechanism, suppressed basal and H(2)O(2)-induced
      apoptosis. We suggest that, progesterone serves to inhibit proliferation of
      ovarian surface epithelial cells throughout the luteal phase--providing the time
      (growth arrest) required to correct any metabolic disturbances to DNA that are
      perpetrated as an inevitable by-product of the ovulatory process. With luteolysis
      and dominance of an estrogenic preovulatory follicle the ovarian surface
      epithelium is then regenerated. Thus, it is conceivable that perturbations to the
      steroid hormonal milieu of ovarian cycles could be a predisposing factor for
      cancerous transformation of an ovarian surface epithelial cell.

PMID- 11850123
TI  - Vitamin D-mediated growth inhibition of an androgen-ablated LNCaP cell line model
      of human prostate cancer.
AB  - 1,25-(OH)(2) vitamin D(3) (1,25-(OH)(2) D), the active metabolite of vitamin D,
      exerts antiproliferative effects on a variety of tumor cells including prostate.
      This inhibition requires vitamin D receptors (VDRs) as well as downstream effects
      on the G1 to S phase checkpoint of the cell cycle. Recent data raise the
      possibility that androgen plays a role in the antiproliferative effects of 1,25
      (OH)(2) D in prostate cancer cells; however, this hypothesis has been difficult
      to test rigorously as the majority of prostate cancer cell lines (unlike human
      prostate tumors) lack androgen receptors (ARs). We utilized two different models
      of androgen-independent prostate cancer that express functional ARs and VDRs to
      evaluate a possible role of androgen in 1,25-(OH)(2) D mediated growth
      inhibition. We stably introduced the AR cDNA into the human prostate cancer cell
      line ALVA 31, which expresses functional VDR but is relatively resistant to
      growth inhibition by 1,25-(OH)(2) D. Neither ALVA-AR nor the control cells, ALVA
      NEO, exhibited substantial growth inhibition by 1,25-(OH)(2) D in the presence or
      absence of androgen. This observation suggests that the basis for the resistance
      of ALVA 31 to 1,25-(OH)(2) D-mediated growth inhibition is not the lack of AR.
      The second model was LNCaP-104R1, an AR-expressing androgen independent prostate
      cancer cell line derived from androgen dependent LNCaP. 1,25-(OH)(2) D inhibited
      the growth of LNCaP-104R1 cells in the absence of androgen and this effect was
      not blocked by the antiandrogen Casodex. As was observed in the parental LNCaP
      cells, this effect was correlated with G1 phase cell cycle accumulation and
      upregulation of the cyclin dependent kinase inhibitor (CKI) p27, as well as
      increased association of p27 with cyclin dependent kinase 2. These findings
      suggest that the antiproliferative effects of 1,25-(OH)(2) D do not require
      androgen-activated AR but do involve 1,25-(OH)(2) D induction of CKIs required
      for G1 cell cycle checkpoint control.

PMID- 11850124
TI  - Proline-rich tyrosine kinase 2 regulates proliferation and differentiation of
      prostate cells.
AB  - Proline-rich tyrosine kinase 2 (Pyk2) expression in prostate epithelium inversely
      correlated with degree of malignancy of prostate cancers, thus the role of Pyk2
      in the regulation of prostate cells proliferation and differentiation was
      investigate in PC3 cells. Pyk2 can be activated by canonic stimuli such as tumor
      necrosis factoralpha and lysophosphatidic acid (LPA) in PC3 cells, in addition,
      LPA stimulated Pyk2 phosphorylation also induced extracellular signal-regulated
      kinase 1 and 2 activation in these cells. Proliferation of PC3 cell clones (PC3
      PKM) expressing a dominant negative kinase-defective Pyk2 mutant is consistently
      decreased in respect to that of wild type PC3 cells. In addition, PC3-PKM clones
      underwent total block cell proliferation upon treatment with dibutyryl cAMP.
      Finally, in the presence of sustained levels of intracellular cAMP, PC3-PKM
      cells, but not wild type PC3 cells, acquired a neuron-like morphology. Taken
      together our results suggest that Pyk2 plays a role in the regulation of prostate
      cell proliferation and, more interestingly, its expression may represents a
      sensitive marker of prostate state of differentiation.

PMID- 11850125
TI  - Dietary genistein down-regulates androgen and estrogen receptor expression in the
      rat prostate.
AB  - The incidence of clinically manifested prostate cancer is higher in the United
      States and Europe than in Asian countries. One of the major differences in
      lifestyle between these populations is the diet, with Asians consuming a greater
      amount of soy. Soy and genistein, the predominant isoflavone found in soy,
      inhibit prostate tumor development in animal models. The purpose of this study
      was to investigate the effect of dietary genistein on sex steroid receptor
      expression in the dorsolateral prostate, on circulating androgens, and the
      potential for toxicity in the male rat reproductive tract. Male Sprague-Dawley
      rats were fed 25 and 250 mg genistein/kg diet from conception until day 70
      postpartum, or 250 and 1000 mg genistein/kg diet from day 56 to 70 postpartum.
      Exposure to genistein in the diet, starting at conception, resulted in down
      regulated androgen receptor (AR), and estrogen receptors (ER)-alpha and -beta
      mRNA expression in the dorsolateral prostate in a dose-dependent manner. Also,
      genistein fed to adult rats for 2 weeks reduced mRNA expression of AR, ER-alpha
      and ER-beta in the dorsolateral prostate. ER-alpha protein levels were
      significantly reduced in animals fed 1000 mg genistein/kg diet compared to
      control animals. There were no significant alterations to male reproductive tract
      histomorphology or weights. We conclude that dietary genistein down-regulated
      expression of the AR and ER-alpha and -beta in the rat prostate at concentrations
      comparable to those found in humans on a soy diet. Down-regulated sex steroid
      receptor expression may be responsible for the lower incidence of prostate cancer
      in populations on a diet containing high levels of phytoestrogens.

PMID- 11850126
TI  - 17beta-Estradiol release in the parabrachial nucleus of the rat evoked by
      visceral afferent activation.
AB  - In the present investigation, in vivo microdialysis was used to measure the
      concentration of estrogen in the parabrachial nucleus (PBN) and plasma of male
      and ovariectomized female Sprague-Dawley rats supplemented with either estrogen
      (OVX-E(2)) or saline (OVX-S) following visceral afferent activation. Analysis of
      dialysate samples prior to vagal stimulation and in non-stimulated controls
      revealed a continuous concentration of estrogen in the PBN for all treatment
      groups (male, 38 +/-4 pg ml(-1); OVX-E(2), 38+/-5 pg ml(-1); OVX-S, 33 +/- 4 pg
      ml(-1)). This concentration of estrogen in the PBN was significantly increased
      during vagal stimulation in all groups (male, 64+/-4 pg ml(-1); OVX-E(2), 104+/-9
      pg ml(-1); OVX-S, 80+/-6 pg ml(-1); P<0.05) and returned to pre-stimulation
      values within 2 h following termination of the stimulation. Immunohistochemical
      analysis revealed that estrogen receptor (ERalpha and ERbeta) density in males
      and ovariectomized saline-replaced female rats was significantly lower than that
      of estrogen-replaced female rats. These results suggest that estrogen is released
      into the PBN by an increase in visceral afferent traffic, however, alterations in
      estrogen receptor populations in the PBN may contribute to an attenuated
      physiological role of estrogen in the PBN of male and saline-replaced
      ovariectomized female rats.

PMID- 11850127
TI  - Evidence for calcium-sensing receptor mediated stanniocalcin secretion in fish.
AB  - The secretion of parathyroid hormone (PTH) and calcitonin (CT) in mammals are
      both tightly regulated by the prevailing levels of extracellular ionic calcium
      (Ca(2+)). And, it is now widely recognized that both of these Ca(2+) effects are
      mediated exclusively through a seven transmembrane calcium sensing receptor or
      CaR. As in the case of PTH and CT, the secretion of stanniocalcin (STC) in fish
      is tightly regulated by the levels of extracellular Ca(2+). Fish STC functions as
      an anti-hypercalcemic hormone such that a rise in extracellular Ca(2+) above the
      physiological set-point of approximately 1.2 mM provokes an immediate secretory
      response. Whether or not Ca(2+)-regulated STC secretion in fishes is mediated by
      similar type of receptor has never been addressed. Here, we have found that
      Ca(2+)-stimulated STC secretion in salmon is mimicked by CaR mimetics,
      pharmacological agents that increase the sensitivity of the CaR to calcium. NPS
      467, a small organic molecule that acts as a positive allosteric modulator of the
      CaR and alters calciotropic hormone secretion in mammals, was examined for
      effects on serum levels of STC in trout. The IP administration of NPS R-467 had
      time and dose-dependent stimulatory effects on STC secretion that were
      indistinguishable from those of Ca(2+) loading. The effects of NPS 467 were
      stereospecific and had no effects on serum CT. NPS 467 induced STC release was
      also manifested by a downstream physiological response; the inhibition of gill
      calcium transport. A cDNA clone was amplified from a fish corpuscle of Stannius
      cDNA library with high homology to the human CaR. RT-PCR revealed that this
      transcript was also present in gill, kidney, pancreas, brain, muscle and spleen.
      These findings suggest that Ca(2+)-stimulated STC secretion in fishes is mediated
      by a calcium ion-sensing receptor similar to that in mammals.

PMID- 11850128
TI  - Cyclic-adenosine 3',5'-monophosphate-stimulated c-fos gene transcription involves
      distinct calcium pathways in single beta-cells.
AB  - In beta-cells activation of the cyclic AMP (cAMP)-signaling cascade stimulates c
      fos mRNA expression, which involves cAMP- and Ca(2+)-mediated mechanisms. To
      delineate potential crosstalk between both pathways at the transcriptional level
      we simultaneously measured c-fos promoter-driven enhanced green fluorescent
      protein (EGFP) expression and cytosolic free calcium ([Ca(2+)](i)) in single beta
      cells (HIT-T15). Forskolin stimulated a rapid rise in cellular cAMP and in
      [Ca(2+)](i) through activation of voltage-sensitive Ca(2+)-influx and enhanced
      wild-type c-fos promoter-driven EGFP (pF711d2EGFP) expression about 4-fold after
      6 h. The voltage-sensitive Ca(2+) channel (VSCC)-blocker nifedipine, which
      completely blocked the forskolin-induced rise in [Ca(2+)](i), partially inhibited
      the forskolin-induced increase in pF711d2EGFP expression, while it was completely
      abolished in Ca(2+)-free medium. VSCC-dependent Ca(2+)-influx per se when
      stimulated by K(+) (45 mM) increased pF711d2EGFP expression only minimally. No
      correlations could be delineated between the forskolin-induced amplitude of the
      Ca(2+) signal and the expression of pF711d2EGFP at the single cell level, which
      may indicate that small rises in [Ca(2+)](i) are sufficient to fully activate the
      Ca(2+)-dependent pathways required for cAMP-dependent c-fos promoter regulation.
      In experiments with various deletion constructs of the c-fos promoter, it could
      be shown that cAMP-mediated activation of the c-fos promoter involves both the
      cAMP-responsive element (CRE) and the serum-responsive element (SRE). While
      nifedipine completely abrogated the cAMP-dependent activation of c-fos
      transcription via the SRE, the CRE-mediated effect of cAMP on the c-fos promoter
      remained unaffected by nifedipine. Thus, cAMP and Ca(2+) are required for full c
      fos promoter activation by the cAMP-signaling pathway in beta-cells. cAMP
      dependent Ca(2+)-influx through VSCC is crucial for c-fos gene transcription via
      the SRE, whereas cAMP-mediated activation of the CRE demands Ca(2+)-influx, which
      is distinct from voltage-sensitive Ca(2+)-influx. This indicates a complex
      interplay between cAMP and Ca(2+) in controlling c-fos gene transcription and
      suggests that the mode of Ca(2+) entry may differentially act on signaling
      pathways leading to gene transcription in beta-cells.

PMID- 11850129
TI  - Caffeine dependence in teenagers.
AB  - This study identifies and characterizes symptoms of caffeine dependence in
      adolescents. Thirty-six adolescents who consumed caffeine daily and had some
      features of caffeine dependence on telephone screen were scheduled for outpatient
      evaluation. Evaluation included the Diagnostic Interview Schedule for Children-IV
      Youth Version (DISC-IV) and modified DISC-IV questions that assessed caffeine
      dependence based on DSM-IV substance dependence criteria. Of 36 subjects, 41.7%
      (n=15) reported tolerance to caffeine, 77.8% (n=28) described withdrawal symptoms
      after cessation or reduction of caffeine intake, 38.9% (n=14) reported desire or
      unsuccessful attempts to control use, and 16.7% (n=6) endorsed use despite
      knowledge of physical or psychological problems associated with caffeine. There
      was no significant difference in the amount of caffeine consumed daily by
      caffeine dependent versus non-dependent teenagers. These findings are important
      due to the vast number of adolescents who drink caffeinated beverages.

PMID- 11850130
TI  - Incidence of alcohol dependence among drunken drivers.
AB  - To discriminate 'alcoholics' and 'non-alcoholics', individual Alc-Indices
      (determined by methanol, acetone, 2-propanol, gamma-GT and CDT-concentrations)
      were calculated in a collective of 327 alcohol-impaired drivers with regard to
      the blood alcohol concentration, the time of the event and the age of the
      drivers. Applying this new defined Alc-Index, 48% of the drivers investigated
      could be characterised as alcohol dependent. The prevalence of alcoholics among
      individuals with blood alcohol concentrations (BAC) higher than 1.9per thousand
      was more than 80%. The diagnostic value of alcohol concentrations for the
      recognition of 'alcoholics', considering the legal limit in Germany (1.1per
      thousand) as well as statistically calculated limits, were compared to the Alc
      Index.

PMID- 11850131
TI  - Changing patient characteristics with increased methadone maintenance
      availability.
AB  - Over the past several years there have been repeated calls for expansion of
      availability of methadone maintenance in several jurisdictions. Important
      stakeholders in the expansion of methadone maintenance treatment (MMT) are
      existing treatment providers. This study describes the impact of the rapid
      expansion in treatment availability in Ontario on the long-standing MMT program
      of the Centre for Addiction and Mental Health (CAMH). This expansion occurred
      through enlarging existing treatment programs, the provision of MMT in private
      physicians' offices and the establishment of new clinics. With expansion in the
      community, demand for the clinic-based treatment of the CAMH MMT program did not
      drop, in fact the patient population was able to continue to grow. There was a
      broadening of the patient profile in the program including patients who were
      better educated, more likely to be employed and less likely to be currently
      injecting (although with a significant history of past injection drug use).
      Moreover, in the face of these changes, excellent treatment retention was
      maintained. This suggests that the expansion in treatment availability did not
      impact negatively on the existing program but rather enabled access for a group
      of higher functioning opioid dependent patients who were previously being
      deterred from treatment entry by the large waiting lists and the need for
      priority access for pregnant and HIV positive heroin users. These findings should
      provide encouragement for MMT providers in jurisdictions anticipating or
      undergoing expansion of treatment availability.

PMID- 11850132
TI  - Changes in use of crack cocaine after drug misuse treatment: 4-5 year follow-up
      results from the National Treatment Outcome Research Study (NTORS).
AB  - Crack cocaine outcomes at 4-5 years are reported for 496 drug users recruited
      from UK treatment programmes. About one-third used crack at intake and at 4-5
      years. The results show different outcome profiles. For crack users at intake,
      use was more than halved at follow-up. Among non-crack-users at intake, about a
      quarter used crack during follow-up, of whom about two-thirds had never used
      crack before. Polydrug use and use of other stimulants were associated with using
      crack. Crack users reported worse acquisitive crime and psychological health
      outcomes. About 10% reported injecting crack. The reductions in crack use are
      encouraging, but the onset of crack use among many non-users at intake suggests
      the need to develop more effective treatment interventions.

PMID- 11850133
TI  - Violence among individuals in substance abuse treatment: the role of alcohol and
      cocaine consumption.
AB  - This study examined factors associated with expressed violence in the 90 days
      prior to substance abuse (SA) treatment among 125 men and 125 women recently
      enrolled in treatment. Approximately 85% of the sample reported a significant
      conflict situation, and over 32% reported an incident of physical violence. Both
      general alcohol and cocaine use patterns (on days not involving significant
      interpersonal conflict), as well as alcohol and cocaine use on the day of the
      violent incident, were associated with violence severity. Regression analyses
      revealed that race, education, age, and both general drinking and cocaine use
      patterns were associated with violence severity for the most severe violent
      incident reported. Similarly, regression analyses focusing on alcohol and cocaine
      use on the day of the most severe incident revealed that higher drinking levels,
      younger age, minority status, and the interaction of alcohol and cocaine use were
      associated with violence severity. The results provide important information
      regarding factors associated with expression of violence among men and women in
      SA treatment, and have implications regarding the assessment of violence risk
      factors. Further, the findings suggest that screening and intervention approaches
      for violence-related problems should be routine in SA treatment, and appear to be
      especially indicated for patients reporting alcohol consumption, and co-occurring
      alcohol and cocaine consumption.

PMID- 11850134
TI  - Primary health care professionals' activity in intervening in patients' alcohol
      drinking: a patient perspective.
AB  - AIM: To test the hypothesis that primary health care professionals' activity in
      intervening in patients' alcohol drinking is low. METHOD: A patient questionnaire
      survey after consultation blind to the primary health care professionals.
      Subjects were 1000 16-65 -year-old consecutive patients consulting a general
      practitioner. The response rate was 66.5%. RESULTS: Of all participants 6.3% and
      of excessive drinkers 11.9% were asked about alcohol drinking at the consultation
      in question. Of all 64.7% and of excessive drinkers 52.4% had never been asked
      about drinking. Of all 6.0% and of excessive drinkers 19.0% were advised about
      alcohol drinking at the consultation in question. CONCLUSION: Alcohol drinking is
      rarely brought up in discussion by primary health care professionals, even in the
      case of excessive drinkers.

PMID- 11850135
TI  - Medical service use and financial charges among opioid users at a public
      hospital.
AB  - We examined the prevalence of drug use related infectious complications among
      opioid using or dependent individuals and service charges associated with medical
      care received over a 2-year period at a public hospital. A computerized medical
      record review was used to identify 3147 individuals with diagnoses related to
      opioid use or dependence. Forty-nine percent of these patients were treated for
      bacterial infections and 30% presented for treatment of medical problems arising
      from the effects of the drugs themselves (e.g. drug withdrawal, overdoses, and
      drug-induced psychiatric symptoms). Mean charges were $13393 for these patients,
      nearly 2.5 times the average per patient charges for non-opioid using patients
      during the study period. Patients with diagnoses related to opioid use or
      dependence comprised 2% of the total patient population for this period, yet
      accounted for 5% of total charges. Homeless patients were less likely to have
      used ambulatory services and were more likely than non-homeless patients to have
      used emergency and inpatient services. Early detection of patients with opioid
      use or dependence problems, coupled with effective strategies to engage them in
      ambulatory preventive services, could allow interventions to reduce morbidity and
      associated charges in this patient population. The findings suggest that health
      care providers and policy makers consider policies that promote ambulatory care
      use among opioid users seeking medical care through the public health care
      system.

PMID- 11850136
TI  - A randomized controlled trial of two primary school intervention strategies to
      prevent early onset tobacco smoking.
AB  - In this article, we examine the impact of two universal, grade 1 preventive
      interventions on the onset of tobacco smoking as assessed in early adolescence.
      The classroom-centered (CC) intervention was designed to reduce the risk for
      tobacco smoking by enhancing teachers' behavior management skills in first grade
      and, thereby, reducing child attention problems and aggressive and shy behavior
      known risk behaviors for later substance use. The family-school partnership (FSP)
      intervention targeted these early risk behaviors via improvements in parent
      teacher communication and parents' child behavior management strategies. A cohort
      of 678 urban, predominately African-American, public school students were
      randomly assigned to one of three Grade 1 classrooms at entrance to primary
      school (age 6). One classroom featured the CC intervention, a second the FSP
      intervention, and the third served as a control classroom. Six years later, 81%
      of the students completed audio computer-assisted self-interviews. Relative to
      controls, a modest attenuation in the risk of smoking initiation was found for
      students who had been assigned to either the CC or FSP intervention classrooms
      (26% versus 33%) (adjusted relative risk for CC/control contrast=0.57, 95%
      confidence interval (CI), 0.34-0.96; adjusted relative risk for FSP/control
      contrast=0.69, 95% CI, 0.50-0.97). Results lend support to targeting the early
      antecedent risk behaviors for tobacco smoking.

PMID- 11850137
TI  - Sex differences in the effects of baclofen on the acquisition of intravenous
      cocaine self-administration in rats.
AB  - Baclofen, a GABA(B) agonist, decreases both the maintenance and reinstatement of
      i.v. cocaine-reinforced responding in rats. In the present experiment the effects
      of baclofen were extended to a comparison of male and female rats during the
      acquisition of i.v. cocaine self-administration. Four groups of rats were trained
      to self-administer i.v. cocaine (0.2 mg/kg) under a fixed-ratio 1 (FR 1) schedule
      using an autoshaping procedure. The criterion for acquisition was a 5-day period
      during which a mean of 100 cocaine infusions were administered. Rats were given
      30 days to reach this criterion. Male and female groups (n=10-13) were pretreated
      with i.p. injections of baclofen (2.5 mg/kg) or vehicle 30-min prior to the
      sessions. A subset of rats (N=5) that did not acquire cocaine self-administration
      continued to be exposed to the acquisition procedure after baclofen treatment
      ended. Pretreatment with baclofen decreased both the rate of acquisition of
      cocaine self-administration and the percentage of rats meeting the acquisition
      criterion to a greater extent in females than in males. Female rats that did not
      meet the acquisition criterion with baclofen treatment, acquired within a few
      days after treatment ended. The findings confirm previous reports of enhanced
      acquisition of cocaine self-administration in females versus males, and they
      indicate that baclofen suppressed the acquisition of cocaine self-administration
      significantly more in females than in males.

PMID- 11850138
TI  - Subjective quality of life and depressive symptoms in women with alcoholism
      during detoxification treatment.
AB  - The study investigated whether subjective quality of life (SQOL) differs in
      alcoholic women with and without depressive symptoms being in detoxification
      treatment. Moreover, we tested whether depressive symptoms were correlated with
      other subjective evaluation criteria. SQOL and psychopathology were obtained in
      70 alcoholic women during treatment. Alcoholic women with depressive symptoms
      showed a lower SQOL regarding several life domains, in particular their family
      situation, and life as a whole. Additionally, they reported more needs for
      support and more negative consequences of alcoholism. The findings underline the
      relevance of quality of life ratings in detoxification treatment and their
      association with depressive symptoms.

PMID- 11850139
TI  - Chronic exposure to morphine, cocaine or ethanol in rats produced different
      effects in brain cannabinoid CB(1) receptor binding and mRNA levels.
AB  - Recent evidence suggest that the endocannabinoid system might be a component of
      the brain reward system and, then, play a role, not only in cannabinoid
      tolerance/dependence, but also in dependence/withdrawal to other drugs of abuse.
      However, there are not many studies that compare the changes in endocannabinoid
      ligands and/or receptors in brain regions (particularly in those areas related to
      reinforcement processes) during dependence to opiates, cocaine or alcohol. The
      present study addressed this objective, by examining the changes in CB(1)
      receptor binding (measured by [3H]-CP55,940 autoradiography) and its mRNA levels
      (measured by in situ hybridization) in different brain regions of animals
      chronically exposed to morphine, cocaine or ethanol. The results showed that
      these three drugs produced different changes in CB(1) receptor binding and mRNA
      levels, a finding that precludes the existence of a common alteration of the
      endocannabinoid system during dependence states to these habit-forming drugs.
      Thus, chronic ethanol exposure was usually uneffective in altering both CB(1)
      receptor binding and mRNA levels in all regions examined. In contrast, chronic
      cocaine exposure produced significant changes only at the level of CB(1) receptor
      mRNA, with decreases of the transcript levels in the ventromedial hypothalamic
      nucleus and the superficial and deep layers of the cerebral cortex, but no
      changes in the hippocampal, motor and limbic structures. Finally, chronic
      morphine exposure increased the density of CB(1) receptors in the medial caudate
      putamen, but decreased their mRNA levels in this region and also in the lateral
      caudate-putamen and the cerebellum. In limbic structures, chronic morphine
      exposure increased both binding and mRNA levels for CB(1) receptors in the septum
      nuclei. Binding was also increased in the nucleus accumbens, but reduced in the
      basolateral amygdala. In hippocampal structures, chronic morphine exposure
      reduced CB(1) receptor binding in the dentate gyrus, although mRNA levels were
      unaffected in this region, but increased in the CA2 subfield of the Ammon's horn.
      The results indicate that mechanisms of dependence for alcohol, cocaine and
      morphine are different in terms of their impact on the endocannabinoid system.
      Alcohol did not produce any effects on CB(1) receptor binding and mRNA levels,
      whereas cocaine only affected transcript levels in selected regions and morphine
      produced divergent and region-dependent effects.

PMID- 11850140
TI  - Rearrest rates among Norwegian drugged drivers compared with drunken drivers.
AB  - The rearrest rates among Norwegian drugged (n=1102) and a group of drunken
      drivers (n=850) (BAC: 0.16-0.19%) apprehended during 1992, were 57% (n=629) and
      28% (n=238), respectively, when followed prospectively for 7 years. The most
      important risk factors for recidivism among drugged drivers were previous arrests
      for drugged or drunken driving (rearrest rate among previous arrests: 73%, no
      previous arrest: 42%), multi-drug detection at selection (multi-drug: 62%, single
      drug: 41%), sex (male: 61%, female: 35%) and age (below 36 years: 60%, 36 years
      and older: 44%). Most of the recidivist drugged drivers were rearrested during
      the year of selection (21%), followed by 13, 7 and 6%, retrospectively, during
      the following years. When followed both retrospectively and prospectively for a
      period extending from 1984 to 1998, 71% (n=779) and 40% (n=344) of the selected
      drugged and drunken drivers, respectively, were arrested two or more times.

PMID- 11850141
TI  - Analysis of the reinforcing and subjective effects of different doses of nitrous
      oxide using a free-choice procedure.
AB  - The reinforcing and subjective effects of five doses of nitrous oxide (0, 10, 20,
      30, 40% N(2)O in O(2)) were studied in 20 non-drug-abusers using a free-choice
      procedure. During each of five sessions, subjects sampled a dose of N(2)O and
      100% O(2) (placebo) for 10 min each. Later they chose nine times, once every 5
      min, among N(2)O (e.g. 'Agent A'), placebo (e.g. 'Agent B'), or a no-drug option.
      Mean preference ratios (N(2)O choices/[N(2)O choices+placebo choices]) and total
      N(2)O choice increased with increasing N(2)O dose. Individual preference ratios
      suggested that at least one active dose of N(2)O functioned as a reinforcer in
      80% of subjects, and the doses that functioned as reinforcers varied across
      subjects. N(2)O choice was positively correlated with end-of-session and post
      session ratings of N(2)O liking and of wanting to inhale N(2)O again, but not
      with ratings of those effects during sampling. Placebo was chosen significantly
      less than the no-drug option, even though both were 100% O(2). More robust
      reinforcing effects of N(2)O were observed in this subject population than in
      previous studies. Choice data emphasize the importance of examining a range of
      doses, and of examining those effects within-subject, when assessing reinforcing
      effects of drugs. Inclusion of the no-drug option eliminated the 'forced' choice
      of placebo, making preference ratios easier to interpret than in previous, forced
      choice procedures. Reinforcing effects were more correlated with subjective
      effects assessed after the session than with subjective effects obtained while
      subjects were under the influence of the drug.

PMID- 11850142
TI  - Male rats exposed to cocaine in utero demonstrate elevated expression of Fos in
      the prefrontal cortex in response to environment.
AB  - Prenatal cocaine exposure has been associated with disruption in attention and
      short-term memory in exposed children and in animal models. The biochemical
      change or changes responsible for these cognitive deficits are not known. An
      intriguing possibility, however, is that cocaine exposure during development
      disrupts the morphology or function of the frontal cortex, a region thought to
      contribute to cognitive and executive functions. In this report, we examined the
      effects of intravenous prenatal cocaine exposure on the expression of the
      immediate-early gene, c-fos, in the adolescent offspring to determine potential
      sites of disruption. The expression of Fos protein was similar in unhandled rats
      prenatally treated with saline or cocaine. Prenatal cocaine exposed rats that
      were handled, but not footshocked, however, demonstrated a dramatic selective
      increase in Fos expression in the ventral and medial prefrontal cortex. A
      footshock-induced increase in Fos expression in the prefrontal cortex was noted
      in prenatal saline, but not prenatal cocaine rats. Interestingly, no differences
      were noted in baseline or footshock-induced increased Fos expression in nuclei of
      the amygdala in prenatal cocaine and prenatal saline rats, indicating some aspect
      of the central response to stress appear unchanged. The unusual activation of the
      neurons of the medial and ventral prefrontal cortex may be a consequence of in
      utero cocaine exposure that contributes to the reported deficit in cognition.

PMID- 11850144
TI  - Amphetamine-induced dopamine release and post-synaptic specific binding in
      patients with mild tardive dyskinesia.
AB  - Several lines of evidence suggest that changes in dopamine release and/or post
      synaptic sensitivity may be involved in the pathogenesis of tardive dyskinesia
      (TD). Preclinically, increased D(2) receptor sensitivity and dopamine turnover
      are associated with D(2) receptor antagonism. Clinically, development of TD is
      associated with D(2) receptor antagonist administration. Eight patients with mild
      evidence of TD (AIMS ratings > or =14) and six without (AIMS = 10), underwent
      [(11)C]raclopride PET scans. Baseline and amphetamine-induced decrements in
      striatal specific binding were assessed. Baseline and amphetamine-induced
      decrements in specific binding did not differ between patients with and without
      evidence of mild TD (p =.53). AIMS ratings did not significantly correlate with
      baseline (p =.76) or decrements in specific binding (p =.45). This study provides
      evidence that TD is not associated with increased amphetamine-induced presynaptic
      dopamine release and/or D(2) receptor binding as measured by [(11)C]raclopride
      PET. More research is needed to unravel the neurobiology of this debilitating
      disorder.

PMID- 11850143
TI  - Exposure to repeated, intermittent d-amphetamine induces sensitization of HPA
      axis to a subsequent stressor.
AB  - Previous studies have demonstrated that exposure to psychostimulant drugs can
      produce a lasting cross-sensitization to the behavioral effects of stress. The
      main purpose the present study was, therefore, to determine the effects of
      psychostimulant cross-sensitization on the stress-induced release of
      adrenocorticotropic hormone (ACTH) and corticosterone (CORT). Rats were given a
      series of injections of d-amphetamine or vehicle in a regimen that has been shown
      previously to induce cross-sensitization to a stressor. After two weeks, half the
      animals in the drug and vehicle-treated conditions were subjected to 30 min
      restraint stress; the remaining animals served as non-stressed controls. Animals
      were then sacrificed and trunk blood was assayed for CORT and ACTH. Prior d
      amphetamine had no effect upon levels of CORT and ACTH in the non-stressed
      animals. Following 30 min restraint stress, however, levels of both hormones were
      significantly higher in drug-treated animals compared to controls. A second
      experiment confirmed behavioral sensitization to the current schedule of d
      amphetamine injections, and demonstrated neuroendocrine sensitization of ACTH and
      CORT to a subsequent drug challenge. The augmented release of CORT and ACTH
      observed in d-amphetamine-treated rats might have important implications for
      human disorders in which processes resembling neurochemical sensitization have
      been hypothesized to play an etiological role.

PMID- 11850145
TI  - Attenuation of acute morphine withdrawal in the neonatal rat by the competitive
      NMDA receptor antagonist LY235959.
AB  - The present study examined the ability of LY235959, a competitive N-methyl-D
      aspartate (NMDA) receptor antagonist, to attenuate behaviors and c-fos mRNA
      expression associated with acute morphine withdrawal in the infant rat. Rat pups
      were given a single dose of morphine (10.0 mg/kg, s.c.) or saline. Two hours
      later, pups were removed from the dam and injected with either LY235959 (10.0
      mg/kg, s.c.) or saline. Fifteen minutes later acute morphine withdrawal was
      precipitated with naltrexone (10.0 mg/kg, s.c.) and behaviors were recorded every
      15 s for the next 60 min. Immediately after behavioral testing, brain and spinal
      cord were assayed for c-fos mRNA analysis by solution hybridization. The
      intensity of the morphine withdrawal syndrome was reduced in pups pre-treated
      with LY235959. Withdrawal behaviors such as head moves, moving paws, rolling, and
      walking were decreased, and vocalizations were completely eliminated in pups pre
      treated with LY2359559. Acute morphine withdrawal increased c-fos mRNA expression
      in the brain and the spinal cord, which was attenuated by pre-treatment of
      LY235959. Thus, in the 7-day-old rat, as in the adult, NMDA receptors play a role
      in the behavioral and molecular manifestations of acute morphine withdrawal.

PMID- 11850146
TI  - 5-HT2A and 5-HT2C/2B receptor subtypes modulate dopamine release induced in vivo
      by amphetamine and morphine in both the rat nucleus accumbens and striatum.
AB  - In vivo microdialysis and single-cell extracellular recordings were used to
      assess the involvement of serotonin(2A) (5-HT(2A)) and serotonin(2C/2B) (5
      HT(2C/2B)) receptors in the effects induced by amphetamine and morphine on
      dopaminergic (DA) activity within the mesoaccumbal and nigrostriatal pathways.
      The increase in DA release induced by amphetamine (2 mg/kg i.p.) in the nucleus
      accumbens and striatum was significantly reduced by the selective 5-HT(2A)
      antagonist SR 46349B (0.5 mg/kg s.c.), but not affected by the 5-HT(2C/2B)
      antagonist SB 206553 (5 mg/kg i.p.). In contrast, the enhancement of accumbal and
      striatal DA output induced by morphine (2.5 mg/kg s.c.), while insensitive to SR
      46349B, was significantly increased by SB 206553. Furthermore, morphine (0.1-10
      mg/kg i.v.)-induced increase in DA neuron firing rate in both the ventral
      tegmental area and the substantia nigra pars compacta was unaffected by SR 46349B
      (0.1 mg/kg i.v.) but significantly potentiated by SB 206553 (0.1 mg/kg i.v.).
      These results show that 5-HT(2A) and 5-HT(2C) receptors regulate specifically the
      activation of midbrain DA neurons induced by amphetamine and morphine,
      respectively. This differential contribution may be related to the specific
      mechanism of action of the drug considered and to the neuronal circuitry involved
      in their effect on DA neurons. Furthermore, these results suggest that 5-HT(2C)
      receptors selectively modulate the impulse flow-dependent release of DA.

PMID- 11850147
TI  - Atypical, but not typical, antipsychotic drugs increase cortical acetylcholine
      release without an effect in the nucleus accumbens or striatum.
AB  - The role of acetylcholine (ACh) in the action of antipsychotic drugs (APDs) was
      studied by microdialysis, without AChesterase inhibition, to facilitate the
      interpretation of any observed drug effects. The atypical APDs, clozapine (2.5-20
      mg/kg), olanzapine (10 mg/kg), risperidone (1 mg/kg), and ziprasidone (3 mg/kg)
      significantly increased ACh release in rat medial prefrontal cortex (mPFC),
      whereas the typical APDs, haloperidol (0.1-1 mg/kg), S(-)-sulpiride (10-25 mg/g),
      and thioridazine (5-20 mg/kg) did not. None of seven APDs increased ACh release
      in the nucleus accumbens or striatum at the doses effective in the mPFC. Thus,
      atypical and typical APDs may differ in the ability to increase cortical ACh
      release, a possible factor contributing to cognitive improvement in
      schizophrenia. After perfusion with neostigmine, an AChesterase inhibitor,
      clozapine, but not haloperidol, increased ACh release in all three aforementioned
      brain regions with an enhanced effect in the mPFC, indicating the importance of
      studying ACh release in the absence of AChesterase inhibition. Clozapine, and
      perhaps other atypical APDs, alone or in combination with an AChesterase
      inhibitor, may improve cognition in schizophrenia, and perhaps other cognitive
      disorders, e.g., early Alzheimer's disease, by enhancing cortical cholinergic
      transmission.

PMID- 11850148
TI  - Depletion of 5-HT disrupts prepulse inhibition in rats: dependence on the
      magnitude of depletion, and reversal by a 5-HT precursor.
AB  - The 5-HT(1A) agonist 8-OH-DPAT has been reported to disrupt prepulse inhibition
      (PPI) of the acoustic startle reflex after local administration into the raphe
      nuclei. Because it is likely that 8-OH-DPAT disrupted PPI by activation of
      somatodendritic inhibitory receptors, and thereby, via a decrease in 5-HT
      neurotransmission, we tested whether chronic, drug-induced, depletions of 5-HT
      have similar effects. Rats were drug-treated for three consecutive days and
      tested in a short PPI paradigm on day 4, and retested 2 h later, after acute
      saline or drug administration. Repeated treatment with the 5-HT synthesis
      inhibitor p-chlorophenylalanine methyl ester (PCPA; 160 mg/kg) produced a small,
      but significant, attenuation of PPI, and a large decrease in extracellular 5-HT
      levels in the hippocampus, as measured in independent microdialysis experiments.
      An even larger depletion of 5-HT was obtained by substituting the 3(rd) PCPA
      administration with the 5-HT releaser d-fenfluramine (10 mg/kg); this combined
      treatment nearly abolished PPI in the majority of animals. The involvement of 5
      HT in the latter effects was confirmed by the finding that low doses of the 5-HT
      precursor 5-hydroxy-L-tryptophan reinstated PPI during retest. These data,
      together with recently published studies, provide strong evidence that
      pharmacologically-induced depletion of 5-HT disrupts PPI.

PMID- 11850149
TI  - The competitive NMDA receptor antagonist CPPene stimulates NREM sleep and eating
      in rats.
AB  - Systemic administration of noncompetitive NMDA receptor antagonists, such as MK
      801, produces a period of intoxication followed by non- rapid eye movement (NREM)
      sleep with greatly elevated delta EEG activity. We have hypothesized that the
      delayed NREM delta EEG increase is a homeostatic response to the immediate
      elevated limbic metabolism that these drugs produce. Here we test this hypothesis
      by examining the sleep and EEG effects of CPPene, a competitive NMDA antagonist
      that does not elevate limbic metabolism. We recorded EEG in seven rats following
      mid-dark period systemic injections of saline and three doses of CPPene. CPPene
      did not produce the delayed NREM delta increase. Instead, CPPene increased eating
      time and dose dependently increased NREM sleep duration shortly after injection.
      These differences in sleep EEG response to a competitive versus the
      noncompetitive NMDA antagonists are consistent with the possibility that the
      increased NREM delta following noncompetitive antagonists is a homeostatic
      response to increased limbic metabolism.

PMID- 11850150
TI  - Dissociable hormonal, cognitive and mood responses to neuroendocrine challenge:
      evidence for receptor-specific serotonergic dysregulation in depressed mood.
AB  - Fifteen patients with major depression, dysthymia, or anxiety disorder with
      depressed mood (DSM-IV diagnoses) and 16 controls received single oral doses of
      0.5mg/kg metachlorophenylpiperazine (m-CPP), a 5-HT(2C) agonist, and 10 mg
      ipsapirone, a 5-HT(1A) agonist, according to double-blind, placebo-controlled,
      cross-over design. The groups' levels of cortisol, adrenocorticotrophic hormone
      (ACTH) and prolactin did not differ at baseline. Both 5-HT agonists significantly
      elevated cortisol, ACTH, and prolactin. The cortisol response to ipsapirone was
      significantly blunted in major depression and dysthymia patients. Neuroendocrine
      responses to m-CPP did not differ between groups, but m-CPP selectively increased
      profile of mood states (POMS) depression and tenseness scores in patients. No
      effects of ipsapirone on mood were found. However, ipsapirone impaired memory
      performance in controls, but tended to improve memory performance in patients.
      The results support the evidence for both hypothalamic and possibly hippocampal 5
      HT(1A) receptor desensitisation and non-hypothalamic, 5-HT(2C) receptor
      sensitisation, probably fronto-cortical, in patients with major depression and
      dysthymia.

PMID- 11850151
TI  - Striatal excitatory amino acid transporter transcript expression in
      schizophrenia, bipolar disorder, and major depressive disorder.
AB  - Because abnormalities of glutamatergic neurotransmission in psychiatric illness
      are likely not limited to glutamate receptor expression, we investigated
      expression of excitatory amino acid transporters (EAATs) in the striatum. The
      EAATs, normally expressed in both glia (EAAT1 and EAAT2) and neurons (EAAT3 and
      EAAT4), have previously been implicated in Huntington's disease, amyotrophic
      lateral sclerosis, and schizophrenia. In this study, we investigated striatal
      expression of transcripts encoding EAATs in tissue from mood disordered and
      schizophrenic subjects. With probes designed for the human EAAT1, EAAT2, EAAT3,
      and EAAT4 transcripts, we performed in situ hybridization and detected decreased
      expression of EAAT3 and EAAT4 transcripts in the striatum in bipolar disorder. We
      also detected decreased EAAT3 transcript expression in schizophrenia and
      decreased EAAT4 transcript expression in major depressive disorder. These results
      suggest that changes in striatal transporter mRNA expression are restricted to
      neuronal EAATs and extend the body of evidence implicating abnormal glutamatergic
      neurotransmission in schizophrenia and mood disorders.

PMID- 11850152
TI  - Neural systems and cue-induced cocaine craving.
AB  - We have extended our previous work investigating the neural correlates of cue
      induced cocaine craving through the use of positron emission tomography with
      greater spatial resolution (<4.6 mm), an evocative script, and a pixel-by-pixel
      analysis. Craving and cerebral glucose metabolism were measured after
      presentation of cocaine-related or neutral cues to 11 cocaine abusers. Cocaine
      cues elicited a higher degree of craving than has been previously reported and
      resulted in left hemispheric activation of lateral amygdala, lateral
      orbitofrontal cortex, and rhinal cortex and right hemispheric activation of
      dorsolateral prefrontal cortex and cerebellum. The intensity of activation in
      these areas (except cerebellum), as well as left insula, was also correlated with
      craving. Deactivation occurred in left ventral pole and left medial prefrontal
      cortex. The results suggest that induction of drug craving involves a neural
      network that assigns incentive motivational value to environmental stimuli
      through the coactivation of brain regions that process information about memories
      and emotions.

PMID- 11850153
TI  - The acute and chronic effects of MDMA ("ecstasy") on cortical 5-HT2A receptors in
      rat and human brain.
AB  - While the pre-synaptic effects of 3,4-methylenedioxymethamphetamine (MDMA) on
      serotonin (5-HT) neurons have been studied extensively, little is known about its
      effects on post-synaptic 5-HT(2) receptors. Therefore, cortical 5-HT(2A) receptor
      densities and 5-HT concentration were studied in MDMA treated rats (10 mg/kg
      s.c.). Furthermore, 5-HT(2A) post-synaptic receptor densities in the cerebral
      cortex of recent as well as ex-MDMA users were studied using [123I]R91150 SPECT.
      In rats we observed a decrease followed by a time-dependent recovery of cortical
      5-HT(2A) receptor densities, which was strongly and positively associated with
      the degree of 5-HT depletion. In recent MDMA users, post-synaptic 5-HT(2A)
      receptor densities were significantly lower in all cortical areas studied, while
      5-HT(2A) receptor densities were significantly higher in the occipital cortex of
      ex-MDMA users. The combined results of this study suggest a compensatory
      upregulation of post-synaptic 5-HT(2A) receptors in the occipital cortex of ex
      MDMA users due to low synaptic 5-HT levels.

PMID- 11850154
TI  - Mechanisms underlying the protective potential of alpha-tocopherol (vitamin E)
      against haloperidol-associated neurotoxicity.
AB  - The undesired side-effects of haloperidol treatment include a number of
      extrapyramidal side-effects which have been proposed to result from drug-induced
      damage to the basal ganglia. The drug also causes irregular movements and
      locomotor patterns in experimental animals. Here we show that haloperidol
      treatment in rats is associated with increases in the expression of p53 and the
      ratio of pro-apoptotic (Bax) to anti-apoptotic (Bcl-2/Bcl-x(L)) proteins in the
      hippocampus and caudate putamen (CPu). In addition, haloperidol induces the DNA
      binding activity of the redox-sensitive nuclear factor-kappa B (NF-kappaB) and
      concomitantly upregulates the levels of the phosphorylated form of IkappaBalpha
      protein in vivo. Similar responses are observed when a mouse hippocampal cell
      line (HT-22) is treated with haloperidol and/or vitamin E. Interestingly, all of
      these biochemical effects of haloperidol are significantly attenuated when
      animals or cultured cells are pretreated with alpha-tocopherol (vitamin E).
      Consistent with this, vitamin E is demonstrated to substantially reduce the
      haloperidol-induced impairment of locomotor activity in rats. Collectively, the
      data indicate the usefulness of vitamin E as an adjunct to haloperidol treatment
      and provide initial clues about the underlying molecular mechanisms involved in
      these effects.

PMID- 11850155
TI  - The role of endogenous cortisol in neuroendocrine studies.

PMID- 11850157
TI  - Cortisol/DHEA ratios in depression.

PMID- 11850158
TI  - Stress invalidates reported effects of sodium valproate on brain CRF systems.

PMID- 11850160
TI  - The burden of invasive pneumococcal disease and the potential for reduction by
      immunisation.
AB  - Streptococcus pneumoniae causes invasive disease world-wide and in all age
      groups. The reported incidence varies geographically and is increased in certain
      population groups. The incidence is highest in children less than 2 years and is
      also increased in the elderly. Mortality remains substantial even in the
      developed world despite appropriate antimicrobial therapy. The emergence of
      penicillin-resistant pneumococci highlights the importance of immunisation as a
      means to prevent disease. This review discusses the burden of invasive
      pneumococcal disease, identifies high-risk patients and analyses evidence for
      vaccine efficacy and cost-effectiveness.

PMID- 11850161
TI  - Piperacillin 2 g/tazobactam 0.5 g is as effective as imipenem 0.5 g/cilastatin
      0.5 g for the treatment of acute uncomplicated pyelonephritis and complicated
      urinary tract infections.
AB  - This randomised, double-blind, multicentre trial compared piperacillin/tazobactam
      (2 g/0.5 g/q8h) and imipenem/cilastatin (0.5 g/0.5 g/q8h) as monotherapy in
      patients with acute pyelonephritis or complicated urinary tract infections. In
      total, 237 patients were randomised to receive either piperacillin/tazobactam
      (n=161) or imipenem/cilastatin (n=166). At the early follow-up (=test-of-cure
      visit) 5-9 days after antibiotic therapy, clinical success was noted in 122/147
      (83.0%) piperacillin/tazobactam recipients compared with 123/154 (79.9%)
      imipenem/cilastatin recipients, thus proving that both treatments were equally
      effective. On a descriptive level, an advantage of piperacillin/tazobactam was
      demonstrated. Microbiological success at the early follow-up was 78/135 (57.8%)
      for piperacillin/tazobactam and 70/144 (48.6%) for imipenem/cilastatin. These
      results were confirmed by equivalent success rates on the last therapy day. Both
      drugs were generally well tolerated.

PMID- 11850162
TI  - Pharmacokinetics and pharmacodynamics of meropenem in critically ill patients.
AB  - The pharmacokinetics and pharmacodynamics of meropenem were investigated in 14
      critically ill patients with sepsis. Patients with creatinine clearance (CrCl)
      higher than 50 ml/min received 1 g meropenem three times daily (Group I) and
      patients with CrCl lower than 50 ml/min received 1 g meropenem twice daily (Group
      II). Meropenum concentrations in plasma were determined by high performance
      liquid chromatography with UV detection. The pharmacokinetic parameters differed
      between the two groups as follows, Group I, maximal concentration 56.3 +/- 19.1
      microg/ml; trough concentration 3.3 +/- 2.5 microg/ml; elimination half life 2.5
      +/- 1.2 h; clearance (Cl) 155.8 +/- 40.6 ml/min; MRT 2.2 +/- 0.4 h; steady state
      volume of distribution (V(ss)) 21.7 +/- 5.7 l, and AUC(-8) 119.4 +/- 32.6
      microg/ml h. Group II, maximal concentration 71.1 +/- 5.1 microg/ml; trough
      concentration 3.4 +/- 1.8 microg/ml; elimination half life 3.9 +/- 1.6 h; Cl 77.7
      +/- 15.8 ml/min; MRT 3.5 +/- 0.6 h; V(ss), 17.1 +/- 2.1 l, and AUC(0-12) 230.2 +/
      43.3 microg/ml h. The most frequently isolated bacteria from blood and wound
      infections were Acinetobacter baumanii, Pseudomonas aeruginosa, Klebsiella
      pneumoniae and Escherichia coli; their meropenem minimal inhibitory
      concentrations (MICs) ranged from 0.064 to 3.0 mg/l. In most cases the
      pharmacodynamic parameters, measured as T>MIC index, were higher than 75%. In
      both groups, patients with susceptible pathogens (MIC<1 mg/l) had meropenem
      plasma levels which exceeded the MIC for the whole dosing interval. When
      pathogens were highly resistant (A. baumanii or P. aeruginosa) the T>MIC indices
      were lower.

PMID- 11850163
TI  - Minimal inhibitory concentrations and time-kill determination of moxifloxacin
      against aerobic and anaerobic isolates.
AB  - Moxifloxacin is a new oral 8-methoxy-quinolone with a wide spectrum of activity
      against Gram-negative and anaerobic bacteria, atypical micro-organisms and multi
      resistant Gram-positive bacteria. This study was designed to assess the in vitro
      activity of moxifloxacin against Gram-positive bacteria with different resistance
      patterns, anaerobes and atypical micro-organisms such as Chlamydia and
      Mycoplasma. Moxifloxacin had good activity against Streptococcus pneumoniae with
      all strains inhibited by < or =0.12 mg/l. The minimal inhibitory concentrations
      (MICs) of moxifloxacin for Streptococcus pyogenes and Streptococcus agalactiae
      ranged from 0.03 to 0.5 mg/l while those of ciprofloxacin were about two- to four
      fold higher (MICs=0.12-1 mg/l). Moxifloxacin was poorly active against
      enterococci but its activity against Clostridium and Bacteroides spp. was in the
      same range as that of metronidazole and superior to that of clindamycin.
      Moxifloxacin was substantially more active than both ciprofloxacin and
      sparfloxacin against Chlamydia.

PMID- 11850164
TI  - Apparent plateau in beta-lactamase production among clinical isolates of
      Haemophilus influenzae and Moraxella catarrhalis in the United States: results
      from the LIBRA Surveillance initiative.
AB  - Haemophilus influenzae (n=2791) and Moraxella catarrhalis (n=1249) isolated from
      patient specimens during 1999 were collected from 290 laboratories participating
      in a moxifloxacin surveillance study as part of the LIBRA Surveillance
      initiative. Isolates were tested for in vitro susceptibility to a panel of agents
      suitable for the treatment of respiratory tract infections. beta-Lactamase
      production was identified in 32.2% of H. influenzae and 94.2% of M. catarrhalis.
      These percentages differed by less than 1.5% from results of a study conducted in
      1997-1998 and were similar to results from other recent US surveillance studies.
      Resistance among H. influenzae to trimethoprim-sulphamethoxazole increased
      considerably, from 2% in the 1997-1998 study (n=6588 H. influenzae) to 15.5% in
      the current study. One isolate of H. influenzae had an MIC of 8 mg/l to both
      levofloxacin and moxifloxacin; all other isolates had MICs of < or =0.5 mg/l and
      < or =0.25 mg/l, respectively. beta-Lactamase production was found to confer
      ampicillin resistance in nearly all isolates. For M. catarrhalis, beta-lactamase
      negative isolates had MICs < or =0.12-0.25 mg/l for ampicillin and < or =0.03
      0.12 mg/l for ceftriaxone. In contrast, beta-lactamase production resulted in
      MICs of < or = 0.12->16 mg/l for ampicillin and < or = 0.03-4 mg/l for
      ceftriaxone. All M. catarrhalis had MICs < or =0.12 mg/l for moxifloxacin and <
      or =1 mg/l for levofloxacin. In summary, antimicrobial susceptibilities and the
      prevalence of beta-lactamase production in H. influenzae and M. catarrhalis in
      the United States has remained essentially unchanged from 1997-1998 to 1999.

PMID- 11850165
TI  - Antimicrobial resistance trends in community-acquired respiratory tract pathogens
      in the Western Pacific Region and South Africa: report from the SENTRY
      antimicrobial surveillance program, (1998-1999) including an in vitro evaluation
      of BMS284756.
AB  - From 1998 to 1999, a large number of community-acquired respiratory tract
      isolates of Streptococcus pneumoniae (n=566), Haemophilus influenzae (n=513) and
      Moraxella catarrhalis (n=228) were collected from 15 centres in Australia, Hong
      Kong, Japan, China, the Philippines, Singapore, South Africa and Taiwan through
      the SENTRY Antimicrobial Surveillance Program. Isolates were tested against 26
      antimicrobial agents using the NCCLS-recommended methods. Overall, 40% of S.
      pneumoniae isolates were resistant to penicillin with 18% of strains having high
      level resistance (MIC > or =2 mg/l). Rates of erythromycin and clindamycin
      resistance were 41 and 23%, respectively. Penicillin-resistant strains showed
      high rates of resistance to other antimicrobial agents: 96% to trimethoprim
      sulphamethoxazole (TMP-SMX), 84% to tetracycline and 81% to erythromycin. A
      significant proportion of penicillin-susceptible strains was also resistant to
      erythromycin (21%), tetracycline (29%) and TMP-SMZ (26%). Small numbers of
      strains were resistant to levofloxacin (0.7%), trovafloxacin (0.4%) and
      grepafloxacin (1.3%) where as all strains remained uniformly susceptible to
      quinupristin/dalfopristin and BMS284756 (MIC(90), 0.06 mg/l), a new
      desfluoroquinolone. beta-lactamases were, produced by 20% H. influenzae isolates
      and only rare strains showed intrinsic resistance to amoxycillin. Other beta
      lactam agents showed good activity with rates of resistance less than 2% and all
      isolates showed susceptibility to cefixime, ceftibuten, cefepime and cefotaxime.
      Rates of resistance to tetracycline and chloramphenicol were also relatively low
      at 3%. The majority (98%) of M. catarrhalis isolates was found to be beta
      lactamase-positive and resistant to penicillins, however, resistance to
      erythromycin and tetracycline was also low at 1.8%. Both H. influenzae and M.
      catarrhalis isolates were uniformly susceptible to the new desfluoroquinolone and
      tested fluoroquinolones.

PMID- 11850166
TI  - Induced expression of melittin, an antimicrobial peptide, inhibits infection by
      Chlamydia trachomatis and Mycoplasma hominis in a HeLa cell line.
AB  - As the number of pathogenic microbial strains resistant to different antibiotics
      increases, amphipathic peptides with antimicrobial activity are promising agents
      for the therapy of infectious diseases. This work deals with the effect of an
      amphipathic antimicrobial peptide, melittin, expressed within recombinant plasmid
      vectors, on infection with urogenital pathogens Chlamydia trachomatis and
      Mycoplasma hominis in HeLa cell culture. Recombinant plasmid constructs with the
      melittin gene under the control of the tetracycline-responsive promoter of human
      cytomegalovirus were obtained. We showed inhibition of C. trachomatis and M.
      hominis infection after the introduction of recombinant plasmid vectors
      expressing the melittin gene into the infected cell culture.

PMID- 11850167
TI  - Antimicrobial activities of clarithromycin, gatifloxacin and sitafloxacin, in
      combination with various antimycobacterial drugs against extracellular and
      intramacrophage Mycobacterium avium complex.
AB  - We studied the activities of clarithromycin and fluoroquinolones (gatifloxacin,
      sitafloxacin, levofloxacin) in combination with other antimycobacterial drugs
      against extracellular and intramacrophage Mycobacterium avium complex (MAC).
      Clarithromycin potentiated the activities of rifampicin and rifalazil against
      both extracellular and intramacrophage MAC. In contrast, all the test quinolones
      exhibited antagonistic effects against extracellular MAC when combined with
      either clarithromycin or rifamycins. Such an antagonism was not observed for the
      activity of these combinations against intramacrophage MAC. Combined effects were
      observed with combinations of these fluoroquinolones with either ethambutol or
      streptomycin. Similar profiles were seen for the activities of two-drug
      combinations of clarithromycin or fluoroquinolones with other drugs against
      intramacrophage MAC isolated from pulmonary and disseminated MAC infections.

PMID- 11850168
TI  - Comparison of Etest, agar dilution, broth microdilution and disk diffusion
      methods for testing in vitro activity of levofloxacin against Staphylococcus spp.
      isolated from neutropenic cancer patients.
AB  - The susceptibility to levofloxacin of 194 consecutive staphylococcal (45
      Staphylococcus aureus and 149 coagulase-negative staphylococci) isolates from
      neutropenic patients was determined by Etest and the results compared with those
      obtained using NCCLS-methods (broth microdilution, agar dilution and disk
      diffusion). Overall agreement at +/- 1log(2) dilution for Etest compared with
      broth microdilution and agar dilution was 99.0 and 83.5%, respectively. The Etest
      category agreement with broth microdilution and disk diffusion was 95.9 and
      89.7%, respectively. Comparison of categories with Etest and agar dilution method
      gave only 67.0% absolute categorical agreement, with 29.9% minor errors and 10.7%
      major errors. No very major errors occurred by the four methods tested. Our
      results show that Etest is a valid alternative to the reference NCCLS-methods for
      monitoring the clinical usefulness of levofloxacin against staphylococci isolates
      from neutropenic patients.

PMID- 11850169
TI  - Prevalence of Helicobacter pylori resistance to metronidazole, clarithromycin,
      amoxycillin and tetracycline in Lebanon.
AB  - The aim of this study was to determine the prevalence of antimicrobial resistance
      amongst Helicobacter pylori isolates cultured from gastric biopsies taken during
      routine endoscopies at the American University of Beirut Medical Center in
      Lebanon. Fifty-four consecutively recovered H. pylori isolates were tested
      against metronidazole, clarithromycin, tetracycline and amoxycillin using the
      epsilometer test. Resistance to metronidazole (MIC > 8 mg/l) was found in 29.5%
      of the isolates while resistance to clarithromycin (MIC > or =0.25 mg/l) and
      tetracycline (MIC > or =4 mg/l) was low (4 and 2%, respectively). All isolates
      were susceptible to amoxycillin (MIC < or =8 mg/l). These findings are comparable
      with those reported from Europe and the United States. The prevalence of
      metronidazole resistance in our study was lower than that from other parts of the
      Middle East and the developing world.

PMID- 11850170
TI  - Use of Etests with carbapenems for Gram-negative rods producing beta-lactamases.
AB  - The in vitro activity of imipenem and meropenem on strains of Gram-negative rods
      producing extended-spectrum beta-lactamase (ESBL) and inducible beta-lactamase
      (IBL) was studied using the Etest. In all, 185 strains from the surgical
      intensive care units of four different hospitals were looked at over 2 years. Of
      these, 94 were ESBL producers and 91 were IBL positive. The in vitro
      sensitivities of imipenem and meropenem were 89.7 and 95.1%, respectively,
      against all strains. The imipenem and meropenem sensitivities of Klebsiella spp.
      were 98.4 and 100%, respectively, but imipenem resistance (21.6%) in Pseudomonas
      aeruginosa strains was higher than that of meropenem (10.8%).

PMID- 11850171
TI  - Classification of oral cephalosporins.

PMID- 11850173
TI  - Development and evolution of the eye: Fondation des Treilles, September, 2001.

PMID- 11850175
TI  - Derivation in culture of primordial germ cells from cells of the mouse epiblast:
      phenotypic induction and growth control by Bmp4 signalling.
AB  - Primordial germ cells (PGCs) are the embryonic precursors of the gametes of the
      adult. PGCs derive from cells of the most proximal part of the cup-shaped
      epiblast corresponding to the presumptive region of the extraembryonic mesoderm.
      At 7.2 days post coitum (dpc) a small group of PGCs located at the base of the
      allantois can be recognised due to a strong alkaline phosphatase activity. Thus
      far, scant information was available on the mechanism(s) controlling the lineage
      of PGCs in the mouse embryo. However, results obtained in mice defective for bone
      morphogenetic protein-4 (Bmp4) secreted molecule revealed that this growth factor
      has important functions for the derivation of PGCs from extraembryonic mesoderm
      cells. In this paper, we have studied the effects in culture of Bmp4 on epiblast
      cells obtained from egg-cylinder stage mouse embryos (5.5-6.0 dpc) and PGCs from
      11.5 dpc embryos. We found that Bmp4 treatment enables recruitment of pluripotent
      cells to a PGC phenotype by a multi-step process involving an initial pre
      commitment of epiblast cells and a following stage of PGC phenotypic
      determination. We further provide evidences that Bmp4 may promote the growth of
      gonadal PGCs through a Smad1/4 signalling.

PMID- 11850174
TI  - A quantitative analysis of the kinetics of Gal4 activator and effector gene
      expression in the zebrafish.
AB  - Using a temperature-inducible hsp70:Gal4 activator and UAS:myc-notch1a-intra as
      effector, we determined quantitatively the kinetics of expression of both
      transgenes and analysed the effects of varying their expressivity on several
      phenotypic traits in the developing zebrafish. hsp70:Gal4 is transcribed within
      15 min after temperature-mediated induction, but Gal4 RNA decays rapidly. The
      Gal4 protein was found to be quite stable, as functional Gal4, which was
      detectable 1.5 h after heat shock (HS), persisted for at least 13 h. myc-notch1a
      intra RNA is expressed approximately 1.5 h after HS, but unlike the Gal4 RNA, it
      was found to be very stable; it continues to accumulate during the succeeding 17
      h after HS. Fully penetrant phenotypic effects are obtained after a relatively
      long activator induction with a 30-min HS.

PMID- 11850176
TI  - Transcription of the Drosophila CKI gene dacapo is regulated by a modular array
      of cis-regulatory sequences.
AB  - Organogenesis requires coordination between developmental programs and cell cycle
      progression. The Cip/Kip families of cyclin-dependent kinase inhibitor (CKI) are
      main effectors linking these two programs. In many instances, expression of
      Cip/Kip CKIs are increased abruptly in cells entering their last mitotic cycle,
      suggesting that CKI expression is developmentally regulated. Expression of Dacapo
      (Dap), a Drosophila Cip/Kip CKI, is transiently up-regulated immediately before
      cells enter G1 arrest. Here we report that dap transcription is controlled by
      modular arrays of tissues specific cis-regulatory elements. Furthermore, we
      identified pan-neural Prospero as a regulator of dap transcription in the
      developing nervous system, providing an example how tissue-specific developmental
      programs can be linked to cell cycle progression.

PMID- 11850177
TI  - Overexpression of the secreted factor Mig30 expressed in the Spemann organizer
      impairs morphogenetic movements during Xenopus gastrulation.
AB  - The Spemann organizer secretes several antagonists of growth factors during
      gastrulation. We describe a novel secreted protein, Mig30, which is expressed in
      the anterior endomesoderm of the Spemann organizer. Mixer-inducible gene 30
      (Mig30) was isolated as a target of Mixer, a homeobox gene required for endoderm
      development. The Mig30 gene encodes a secreted protein containing a cysteine-rich
      domain and an immunoglobulin-like domain that belongs to the insulin-like growth
      factor-binding protein family. Overexpression of Mig30 in the dorsal region
      results in the retardation of morphogenetic movements during gastrulation and
      leads to microcephalic embryos. Overexpression of Mig30 also inhibits activin
      induced elongation of ectodermal explants without affecting gene expression
      patterns in mesoderm and endoderm. These results suggest that Mig30 is involved
      in the regulation of morphogenetic movements during gastrulation in the
      extracellular space of the Spemann organizer.

PMID- 11850178
TI  - The synpolydactyly homolog (spdh) mutation in the mouse -- a defect in patterning
      and growth of limb cartilage elements.
AB  - We have investigated the recessive mouse mutant synpolydactyly homolog (spdh) as
      a model for human synpolydactyly (SPD). As in human SPD, the spdh phenotype
      consists of central polydactyly, syndactyly and brachydactyly and is caused by
      the expansion of a polyalanine encoding repeat in the 5' region of the Hoxd13
      gene. We performed a detailed phenotypic and functional analysis of spdh/spdh
      embryos using skeletal preparations, histology, in situ hybridization, BrdU
      labeling of proliferating cells, and in vitro expression studies. The absence of
      normal phalangeal joints and the misexpression of genes involved in joint
      formation demonstrate a role for Hox-genes in joint patterning. The spdh mutation
      results in abnormal limb pattering, defective chondrocyte differentiation, and in
      a drastic reduction in proliferation. Abnormal chondrocyte differentiation and
      proliferation persisted after birth and correlated with the expression of the
      mutant Hoxd13 and other Hox-genes during late-embryonic and postnatal growth.

PMID- 11850179
TI  - Nuclear factor I-B (Nfib) deficient mice have severe lung hypoplasia.
AB  - Binding sites for transcription factor nuclear factor one (NFI) proteins, encoded
      by four genes in the mouse, have been characterized from many tissue-specific
      genes. NFI genes are expressed in unique but overlapping patterns in embryonic
      and in adult tissues. Nfib is highly expressed in the embryonic lung. Here we
      show that Nfib null mutants die early postnatally and display severe lung
      hypoplasia. Heterozygotes do survive, but exhibit delayed pulmonary
      differentiation. Expression of transforming growth factor beta 1 (TGF-beta1) and
      sonic hedgehog (Shh) is not down-regulated in mutant lung epithelium at late
      stages of morphogenesis, which may result in incomplete lung maturation. Our
      study demonstrates that Nfib is essential for normal lung development, and
      suggests that it could be involved in the pathogenesis of respiratory distress
      syndromes in humans.

PMID- 11850181
TI  - New 3' elements control Pax6 expression in the developing pretectum, neural
      retina and olfactory region.
AB  - Pax6 is a key transcriptional regulator in eye, olfactory system, forebrain,
      pituitary cerebellum, spinal cord and pancreas development. Alternative splicing,
      promoter usage and multiple enhancers regulate the complex Pax6 spatio-temporal
      expression pattern. Chromosomal rearrangements which abolish PAX6 gene expression
      have been characterised downstream of the coding region. Through evolutionary
      sequence comparison and transgenic reporter studies, we have identified a new
      Pax6 3' cis-regulatory region. This region, C1170 Box 123, contains three
      distinct modules of human-mouse sequence conservation, while only Box 1 is
      conserved to Fugu. Both the human and the orthologous Fugu sequence direct
      similar reporter gene expression in the developing pretectum, neural retina and
      olfactory region, indicating evolutionary conservation of Pax6 regulatory
      mechanisms despite the low level of overall sequence conservation.

PMID- 11850180
TI  - Proliferative generation of mammalian auditory hair cells in culture.
AB  - Hair cell (HC) and supporting cell (SC) productions are completed during early
      embryonic development of the mammalian cochlea. This study shows that acutely
      dissociated cells from the newborn rat organ of Corti, developed into so-called
      otospheres consisting of 98% nestin (+) cells when plated on a non-adherent
      substratum in the presence of either epidermal growth factor (EGF) or fibroblast
      growth factor (FGF2). Within cultured otospheres, nestin (+) cells were shown to
      express EGF receptor (EGFR) and FGFR2 and rapidly give rise to newly formed
      myosin VIIA (+) HCs and p27(KIP1) (+) SCs. Myosin VIIA (+) HCs had incorporated
      bromodeoxyuridine (BrdU) demonstrating that they were generated by a mitotic
      process. Ultrastructural studies confirmed that HCs had differentiated within the
      otosphere, as defined by the presence of both cuticular plates and stereocilia.
      This work raises the hypothesis that nestin (+) cells might be a source of newly
      generated HCs and SCs in the injured postnatal organ of Corti.

PMID- 11850182
TI  - Deregulated cell cycle control in lens epithelial cells by expression of
      inhibitors of tumor suppressor function.
AB  - Previous studies have shown that cell cycle proteins such as retinoblastoma
      protein (pRB) are essential for cell cycle withdrawal in differentiating lens
      cells. However, little is known about which factors are critical for cell cycle
      control in the lens epithelial cells. Here we use the K14 promoter to direct
      expression of E6 and E7, oncogenes from human papillomavirus type 16, which are
      known to bind and inactivate p53 and pRB, as molecular tools to study cell cycle
      regulation in the lens epithelium of transgenic mice. Expression of either gene
      resulted in increased proliferation and apoptosis, and in the case of E6, a
      unique epithelial phenotype characterized by multilayering and intercellular
      vacuoles was observed. Lenses from mice expressing E7 mutants, which are
      defective in inactivating pRB proteins, were normal and the lens phenotype in the
      E6 mice was p53-independent. Thus, cell proliferation in the lens epithelium is
      controlled by multiple factors including, but not necessarily limited to, the pRB
      family.

PMID- 11850183
TI  - Gene expression profiles in Ciona intestinalis cleavage-stage embryos.
AB  - A total of 1612 expression sequence tags derived from Ciona intestinalis cleavage
      stage embryos were examined to explore detailed gene expression profiles. The 3'
      sequences indicate that the 1612 clones can be categorized into 1066 independent
      clusters. DDBJ database search suggested that 496 of them showed significant
      matches to reported proteins with distinct functions. Among them 69 are
      associated with cell-cell communications and 41 with transcription factors. In
      situ hybridization of all 1066 clusters showed that 84 clusters exhibited
      blastomere-specific pattern of expression, and many of these genes seem to encode
      for novel proteins. One of the interesting findings is that most of them were
      expressed in the precursor cells of multiple tissues. Among them 28 genes were
      expressed in the marginal zone of the 32-cell embryo. The blastomeres in this
      region are thought to receive an inductive signal from the vegetal blastomeres.
      Many of the blastomere-specific genes did not show similarity to known proteins.
      The present analysis therefore provides new information for further analyses on
      the cell fate specification in the Ciona embryo.

PMID- 11850184
TI  - Identification of a transcriptional regulatory region for germline-specific
      expression of vasa gene in Drosophila melanogaster.
AB  - The vasa gene (vas) is essential for germline development in Drosophila
      melanogaster. Zygotic vas is expressed in pole cells earlier than any other pole
      cell-expressing genes thus far identified, and VAS protein is continuously
      present in germline cells throughout development. Here, we report the
      identification of a regulatory region that directs germline-specific vas
      expression. A genomic fragment containing the vas locus was linked to enhanced
      green fluorescent protein (egfp)-vas fusion gene, and the resulting gene was
      introduced into fly genome. Developmental vas expression was assessed by
      monitoring the expression of EGFP-VAS in these transformants. The spatio-temporal
      expression pattern of EGFP-VAS is essentially identical to that of endogenous VAS
      throughout germline development. By dissecting the vas promoter, we identified a
      40-bp regulatory element, which is necessary and sufficient for germline-specific
      expression during oogenesis. This region interacts specifically with ovarian
      protein(s). Furthermore, this region is also required for vas expression in pole
      cells during embryogenesis. These results suggest that a similar mechanism
      regulates vas expression both in oogenesis and embryogenesis.

PMID- 11850185
TI  - Gbx2 interacts with Otx2 and patterns the anterior-posterior axis during
      gastrulation in Xenopus.
AB  - Anterior-posterior patterning of the embryo requires the activity of multiple
      homeobox genes among them Hox, caudal (Cdx, Xcad) and Otx2. During early
      gastrulation, Otx2 and Xcad2 establish a cross-regulatory network, which is an
      early event in the anterior-posterior patterning of the embryo. As gastrulation
      proceeds and the embryo elongates, a new domain forms, which expresses neither,
      Otx2 nor Xcad2 genes. Early transcription of the Xenopus Gbx2 homologue, Xgbx2a,
      is spatially restricted between Otx2 and Xcad2. When overexpressed, Otx2 and
      Xcad2 repress Xgbx2a transcription, suggesting their role in setting the early
      Xgbx2a expression domain. Homeobox genes have been shown to play crucial roles in
      the specification of the vertebrate brain. The border between the transcription
      domains of Otx2 and Gbx2 is the earliest known marker of the region where the
      midbrain/hindbrain boundary (MHB) organizer will develop. Xgbx2a is a negative
      regulator of Otx2 and a weak positive regulator of Xcad2. Using obligatory
      activator and repressor versions of Xgbx2a, we demonstrate that, during early
      embryogenesis, Xgbx2a acts as a transcriptional repressor. In addition, taking
      advantage of hormone-inducible versions of Xgbx2a and its antimorph, we show that
      the ability of Xgbx2a to induce head malformations is restricted to gastrula
      stages and correlates with its ability to repress Otx2 during the same
      developmental stages. We therefore suggest that the earliest known step of the
      MHB formation, the establishment of Otx2/Gbx2 boundary, takes place via mutual
      inhibitory interactions between these two genes and this process begins as early
      as at midgastrulation.

PMID- 11850186
TI  - Localization of transcripts of the zebrafish morphogen Squint is dependent on egg
      activation and the microtubule cytoskeleton.
AB  - The generation of polarity and patterning in multicellular organisms depends in
      part on the asymmetric localization of molecules to specific subdomains within a
      cell. Localized transcripts for several molecules are known to be required for
      patterning oocytes and embryos in Drosophila as well as Caenorhabditis elegans.
      Here, we describe the localization of transcripts encoding the nodal-related
      morphogen, Squint (sqt), in zebrafish oocytes and early embryos, and the
      mechanisms by which sqt RNA is localized. sqt transcripts are uniformly
      distributed in oocytes through all stages of oogenesis. Upon egg activation, sqt
      RNA is localized to the blastoderm, and excluded from the yolk cell. The
      mechanism of sqt RNA transport was examined using cytoskeletal inhibitors.
      Disruption of actin microfilaments by treatment with latrunculin A does not alter
      the localization of sqt RNA to the blastoderm. However, disruption of the
      microtubule cytoskeleton by treatment with nocodazole affects sqt RNA
      localization. These results indicate that sqt transcripts are translocated by an
      RNA localization pathway which is initiated upon egg activation, and that sqt RNA
      localization through this pathway is mediated via the microtubule cytoskeleton.

PMID- 11850187
TI  - Developmental expression profiles of Celsr (Flamingo) genes in the mouse.
AB  - Celsr, also called Flamingo (Fmi) genes encode proteins of the cadherin
      superfamily. Celsr cadherins are seven-pass transmembrane proteins with nine
      cadherin repeats in the extracellular domain, and an anonymous intracellular C
      terminus. The Drosophila Fmi gene regulates epithelial planar cell polarity and
      dendritic field deployment. The three Flamingo gene orthologs in man and rodents
      are named, respectively, CELSR1-3 and Celsr1-3. Celsr1 and 2 are expressed during
      early development, in the brain and epithelia. In this report, we characterized
      further Celsr genes in the mouse, and examined their developmental pattern of
      expression. Each Celsr is expressed prominently in the developing brain following
      a specific pattern, suggesting that they serve distinct functions.

PMID- 11850188
TI  - The expression of SCDGF/PDGF-C/fallotein and SCDGF-B/PDGF-D in the rat central
      nervous system.
AB  - We examined the expression patterns of the two homologous genes, spinal cord
      derived growth factor (SCDGF)/platelet-derived growth factor (PDGF)-C/fallotein
      and SCDGF-B/PDGF-D in the rat central nervous system. In the spinal cord,
      SCDGF/PDGF-C/fallotein was expressed in the floor plate at embryonic day (E) 11
      and also in the ventricular zone at E16 but not in adult. However, SCDGF-B/PDGF-D
      was prominently expressed in the adult motoneurons, although faint expression was
      observed in the ventral ventricular zone at E16. Also in the brain, the
      expression of SCDGF/PDGF-C/fallotein was more remarkable at E16 than at adult. It
      was highly expressed in the cortex, pontine area and choroid plexus at E16.
      Contrary to SCDGF/PDGF-C/fallotein, SCDGF-B/PDGF-D expression was notable in
      several nuclei at adult.

PMID- 11850189
TI  - Prolyl 4-hydroxylase alpha-related proteins in Drosophila melanogaster: tissue
      specific embryonic expression of the 99F8-9 cluster.
AB  - The extracellular matrix (ECM) is proposed to play critical roles in organ
      morphogenesis through the stabilization and/or sequestration of signaling factors
      and adhesion molecules, and by maintaining organ integrity. As a first step
      toward understanding molecules involved in ECM modification and maturation, we
      have examined the embryonic expression profiles of ten prolyl 4-hydroxylase alpha
      subunit (PH4alpha)-related genes. Prolyl 4-hydroxylases (PH4) catalyze the
      formation of 4-hydroxyproline in collagens, the major components of the ECM, and
      are implicated in the hydroxylation of proline in several other secreted
      proteins. To date, two alpha subunit proteins have been described in both humans
      (PHalphaI and PHalphaII) and worms (PHY-1/DPY-18 and PHY-2), whereas only a
      single Drosophila alpha subunit has been identified. The ten PH4alpha-related
      genes described in this study are clustered in a 183-kb region near the tip of
      chromosome arm 3R and include the previously described Drosophila alpha subunit
      gene. Six of the ten PH4alpha genes in the cluster have tissue-specific embryonic
      expression. PH4alphaSG1 and PH4alphaSG2 are expressed in the salivary gland,
      PH4alphaMP is expressed in mouth-part precursors, PH4alphaPV is expressed in the
      proventriculus, and CG9698-E is expressed in the epidermis. PH4alphaEFB is
      expressed more broadly, with expression in the anterior and posterior midgut
      primordia, the fat body, the hemocytes and the epidermis. The expression profiles
      of these PH4alpha-related genes suggest that tissue-specific ECM modifications
      may be critical to organ formation and/or function.

PMID- 11850190
TI  - The ret finger protein-like 4 gene, Rfpl4, encodes a putative E3 ubiquitin
      protein ligase expressed in adult germ cells.
AB  - Using an in silico (electronic database) subtraction, we identified a new member
      of the Ret Finger Protein-Like gene family, Rfpl4. Rfpl4 encodes a 287 amino acid
      putative E3 ubiquitin-protein ligase with a RING finger-like domain and a B30.2
      motif. Reverse transcriptase polymerase chain reaction and Northern blot analyses
      reveal that Rfpl4 encodes a 1.7kb mRNA detectable exclusively in the gonads of
      adult mice. In situ hybridization localizes Rfpl4 transcripts within the ovary to
      oocytes of primary and later stage follicles and in the testis to elongating
      spermatids. The Rfpl4 gene comprises three exons and maps to mouse chromosome 7.
      We have identified the human ortholog, which maps to 19q13.4. These studies
      suggest that RFPL4 mediates protein degradation pathways important for
      gametogenesis or early embryonic development.

PMID- 11850191
TI  - Sox-9 and cDachsund-2 expression in the developing chick telencephalon.
AB  - The expression patterns of the transcription factor, Sox-9, and of the nuclear
      factor, cDachsund-2, were examined in the developing chick telencephalon. Both
      genes were expressed in the ventricular zone and in the subventricular zone of
      the telencephalon during the period of neurogenesis. Whereas Sox-9 was not
      expressed in postmitotic tissues, cDachsund-2 was specifically expressed in the
      neostriatum and in subdivisions of the hyperstriatum embryonically and in
      posthatch chicks.

PMID- 11850192
TI  - Isolation of three zebrafish dachshund homologues and their expression in sensory
      organs, the central nervous system and pectoral fin buds.
AB  - Drosophila dachshund (dac) interacts with sine oculis (so), eyes absent (eya) and
      eyeless (ey) to control compound eye development. We have cloned three zebrafish
      dac homologues, dachA, dachB and dachC, which are expressed widely, in distinct
      but overlapping patterns. Expression of all three is found in sensory organs, the
      central nervous system and pectoral fin buds. dachA is also expressed strongly in
      the somites and dachC in the neural crest and pronephros. These expression
      domains overlap extensively with those of zebrafish pax, eya and six family
      members, the homologues of Drosophila ey, eya and so, respectively. This is
      consistent with the proposal that Dach, Eya, Six and Pax family members may form
      networks, similar to that found in the fly eye, in the development of many
      vertebrate organs.

PMID- 11850193
TI  - Etr-r3/mNapor, encoding an ELAV-type RNA binding protein, is expressed in
      differentiating cells in the developing rodent forebrain.
AB  - The gene encoding human neuroblastoma apoptosis-related RNA binding protein
      (NAPOR) has rat and mouse homologues, Etr-r3 and mNapor, cloned recently by
      ourselves and others. Etr-r3/mNapor is transcribed in embryonic brain but its
      detailed expression patterns are unknown. It has been hypothesised that its
      expression coincides with the occurrence of programmed cell death, but existing
      expression data are insufficient to evaluate this possibility. We used northern
      blots and in situ hybridisation to show that Etr-r3/mNapor is expressed by most
      postmitotic differentiating cells throughout the forebrain during embryogenesis
      and the first weeks of postnatal life. Expression is particularly high in the
      developing cerebral cortex, in nuclei of the ventral telencephalon, in dorsal
      thalamus and in hypothalamus. In contrast, Etr-r3/mNapor is expressed by very few
      cells in proliferative regions, where cell death rates are highest.

PMID- 11850194
TI  - Prox1 is differentially localized during lens development.
AB  - Prox1, the vertebrate cognate of Drosophila Prospero, is a homeodomain protein
      essential for the development of the lens, liver and lymphatic system. While it
      is well established that the subcellular distribution of Prospero changes during
      development, this had not been demonstrated for Prox1. Here, high-resolution
      confocal microscopy demonstrated that Prox1 protein is predominately cytoplasmic
      in the lens placode as well as the lens epithelium and germinative zone
      throughout development. However during fiber cell differentiation, Prox1 protein
      redistributes to cell nuclei. Finally, as lens fiber cells condense their
      chromatin in response to lens denucleation, Prox1 remains in the nucleus but does
      not appear to interact with DNA. Thus, it appears that the function of Prox1,
      like that of its Drosophila cognate Prospero, is at least partially controlled by
      changes in its subcellular distribution during development.

PMID- 11850195
TI  - Isolation and expression of a novel neuron-specific onecut homeobox gene in
      zebrafish.
AB  - A complete cDNA of a novel zebrafish gene named onecut has been isolated; this
      gene encodes a protein of 446 amino acids with a Cut domain (73 amino acid
      residues) and a homeodomain. The Cut domain of zebrafish Onecut is highly similar
      to those in mammalian hepatocyte nuclear factor-6 and Drosophila Onecut, sharing
      90 and 88% amino acid identity, respectively. The expression of zebrafish onecut
      is restricted to neuronal cells, being first detected in trigeminal ganglia
      neurons at the end of gastrulation. By the 1-somite stage, onecut expression has
      begun in primary neurons of the lateral stripes in the neural plate, and appeared
      in neuronal cells of the medial stripes at the 2-somite stage. By the 4-somite
      stage, onecut expression expanded to the intermediate stripes and to subsets of
      neuronal cells in the midbrain and hindbrain. Subsequently, onecut expression
      intensified in the lateral region of midbrain and hindbrain, yet no onecut
      positive cells were seen in the telencephalon. By 24hpf, onecut transcripts
      remained abundant in the spinal cord but were no longer detectable in
      differentiated Rohon-Beard sensory neurons. The expression of onecut was greatly
      increased in the neural mutant mindbomb, while being decreased in narrowminded.

PMID- 11850196
TI  - Cloning and expression of medaka Dachshund.
AB  - The nuclear factor dachshund (dac) is a regulator of retinal cell fate
      determination in Drosophila. We have cloned a Dachshund homologue of a lower
      vertebrate, the teleost medaka (Oryzias latipes). Sequence comparison reveals
      high similarity of medaka Dachshund (OlDach) to the known homologues in higher
      vertebrates and Drosophila. OlDach is first expressed at early somitogenesis
      stages in the otic placode territory and forming somites. Subsequently,
      expression is detected in the retina, specific regions of the central nervous
      system, pancreas and the finbuds.

PMID- 11850197
TI  - Dynamic regulation of Smad expression during mesenchyme to epithelium transition
      in the metanephric kidney.
AB  - Genetic studies have revealed a role for the transforming growth factor beta
      (TGFbeta) superfamily growth factors in development of the mouse kidney. In this
      study, we have characterized developmental expression of Smad proteins, the
      downstream effectors of TGFbeta superfamily ligands. Immunohistochemistry
      detecting Smads 1-5 and 8 was performed on 11.25-15.5 dpc kidney sections. We
      find that Smad proteins are readily detected in metanephric mesenchyme but are
      coordinately down-regulated in condensing mesenchyme and derivative structures
      such as renal vesicles. In order to define the stage at which down-regulation
      occurs, we used the heterologous inducer lithium chloride to promote condensation
      in isolated cultured mesenchymal explants and subsequently assayed expression of
      Smad 4. Down-regulation is complete in lithium chloride induced mesenchymal
      condensates, indicating that Smad regulation takes place at an early stage, prior
      to mesenchyme to epithelium transition.

PMID- 11850198
TI  - The heat-inducible zebrafish hsp70 gene is expressed during normal lens
      development under non-stress conditions.
AB  - In the present study, we show that the stress-inducible hsp70 gene in zebrafish
      is strongly and specifically expressed during normal lens formation from 28 to 38
      hours post-fertilization, and is subsequently downregulated by 2 days of age.
      Only weak constitutive hsp70 mRNA signal was sporadically observed in other
      embryonic tissues. Similarly, transgenic fish carrying a 1.5 kb fragment of the
      hsp70 promoter linked to eGFP exhibited fluorescence only in the lens. In
      contrast, both the endogenous hsp70 gene and the transgene were strongly
      expressed throughout the embryo following heat shock at the same developmental
      stages.

PMID- 11850199
TI  - Microarray analysis of novel cell lines representing two stages of metanephric
      mesenchyme differentiation.
AB  - Clonal cell lines representing different developmental stages of the metanephric
      mesenchyme were made from transgenic mice with the Simian Virus 40 T-antigen
      (SV40 Tag) gene driven by the Hoxa 11 promoter. The resulting mK3 cell line
      represented early metanephric mesenchyme, prior to induction by the ureteric bud.
      These cells showed a spindle-shaped, fibroblast morphology. They expressed genes
      characteristic of early mesenchyme, including Hoxa 11, Hoxd 11, collagen I, and
      vimentin. Moreover, the mK3 cells displayed early metanephric mesenchyme
      biological function. In organ co-culture experiments they were able to induce
      growth and branching of the ureteric bud. Another cell line, mK4, represented
      later, induced metanephric mesenchyme undergoing epithelial conversion. These
      cells were more polygonal, or epithelial in shape, and expressed genes diagnostic
      of late mesenchyme, including Pax-2, Pax-8, Wnt-4, Cadherin-6, Collagen IV, and
      LFB3. To better define the gene expression patterns of kidney metanephric
      mesenchyme cells at these two stages of development, RNAs from the mK3 and mK4
      cells were hybridized to Affymetrix GeneChip probe arrays. Over 4000 expressed
      genes were identified and thereby implicated in kidney formation. Comparison of
      the mK3 and mK4 gene expression profiles revealed 121 genes showing greater than
      a ten-fold difference in expression level. Several are known to be expressed
      during metanephric mesenchyme differentiation, but most had not been previously
      associated with this process. In situ hybridizations were used to confirm that
      selected novel genes were expressed in the developing kidney.

PMID- 11850201
TI  - Aromatase-deficient (ArKO) mice accumulate excess adipose tissue.
AB  - Aromatase is the enzyme which catalyses the conversion of C19 steroids into C18
      estrogens. We have generated a mouse model wherein the Cyp19 gene, which encodes
      aromatase, has been disrupted, and hence, the aromatase knockout (ArKO) mouse
      cannot synthesise endogenous estrogens. We examined the consequences of estrogen
      deficiency on accumulation of adipose depots in male and female ArKO mice,
      observing that these animals progressively accrue significantly more intra
      abdominal adipose tissue than their wildtype (WT) litter mates, reflected in
      increased adipocyte volume and number. This increased adiposity was not due to
      hyperphagia or reduced resting energy expenditure, but was associated with
      reduced spontaneous physical activity levels, reduced glucose oxidation, and a
      decrease in lean body mass. Elevated circulating levels of leptin and cholesterol
      were present in 1-year-old ArKO mice compared to WT controls, as were elevated
      insulin levels, although blood glucose was unchanged. Associated with these
      changes, the livers of ArKO animals were characterised by a striking accumulation
      of lipid droplets. Our findings demonstrate an important role for estrogen in the
      maintenance of lipid homeostasis in both males and females.

PMID- 11850202
TI  - Alternations in hepatic expression of fatty-acid metabolizing enzymes in ArKO
      mice and their reversal by the treatment with 17beta-estradiol or a peroxisome
      proliferator.
AB  - We generated aromatase gene knockout mice (ArKO mice) by targeting disruption of
      Cyp19, which encodes an enzyme responsible for conversion of androgens to
      estrogens. We found that ArKO males developed hepatic steatosis spontaneously
      with aging, indicating that the function of Cyp19 is required to maintain
      constitutive lipid metabolism in male mice. Plasma lipoprotein analysis using a
      gel permeation chromatography revealed that high density lipoprotein (HDL)
      cholesterol levels were slightly higher in ArKO males than in wild-type males,
      whereas no other obvious alternations in the profiles were detected.
      Nevertheless, analysis of lipoprotein compositions by SDS-polyacrylamide gel
      electrophoresis demonstrated apparent reduction in the amounts of apolipoprotein
      E, functioning in receptor-mediated clearance of lipoproteins in the liver, in
      the IDL/LDL fraction of ArKO males as compared with that of wild-type males.
      Biochemical analysis on the ArKO livers revealed suppression of mRNA expression
      and activity of enzymes involved in fatty acid beta-oxidation. The impairment was
      reversed to the wild-type levels by treatment with 17beta-estradiol or
      bezafibrate, the latter is a synthetic peroxisome proliferator. These findings
      indicated a pivotal role of estrogen in supporting constitutive hepatic
      expression of genes involved in fatty acid beta-oxidation and in maintaining
      lipid homeostasis.

PMID- 11850203
TI  - Role of aromatase in endometrial disease.
AB  - Aromatase is the key enzyme for estrogen biosynthesis. It is normally expressed
      in the human ovary, skin, adipose tissue and brain. Aromatase activity is not
      detectable in normal endometrium. In contrast, aromatase is expressed aberrantly
      in endometriosis and is stimulated by PGE2. This results in local production of
      estrogen, which induces PGE2 formation and establishes a positive feedback cycle.
      Another abnormality in endometriosis, i.e. deficient 17beta-hydroxysteroid
      dehydrogenase (17beta-HSD) type 2 expression, impairs the inactivation of
      estradiol to estrone. These molecular aberrations collectively favor accumulation
      of increasing quantities of estradiol and PGE2 in endometriosis. The clinical
      relevance of these findings was exemplified by the successful treatment of an
      unusually aggressive case of post-menopausal endometriosis using an aromatase
      inhibitor.

PMID- 11850204
TI  - Aromatase overexpression transgenic mice model: cell type specific expression and
      use of letrozole to abrogate mammary hyperplasia without affecting normal
      physiology.
AB  - Our recent studies have shown that overexpression of aromatase results in
      increased tissue estrogenic activity and induction of hyperplastic and dysplastic
      lesions in female mammary glands and gynecomastia and testicular cancer in male
      aromatase transgenic mice. Both aromatase mRNA and protein are overexpressed in
      transgenic mammary glands and its expression is not limited to epithelial cells.
      However, it is more in epithelial than in stromal cells. Our results also
      indicate aromatase overexpression-induced changes in mammary glands can be
      abrogated with very low concentrations of the aromatase inhibitor, letrozole. Low
      concentration of letrozole had no effect on normal physiology as indicated by no
      significant change in the circulating levels of estradiol and follicle
      stimulating hormone as well as no change in estrogen responsive genes such as the
      progesterone receptor and lactoferrin in the uterine tissue. These observations
      indicate that the expression of aromatase in both epithelial and stromal cells
      can influence the complex interactions of biochemical pathways leading to mammary
      carcinogenesis and that the aromatase inhibitor, letrozole can be used as
      chemopreventive agents without affecting normal physiology.

PMID- 11850206
TI  - Aromatase and COX-2 expression in human breast cancers.
AB  - We have investigated aromatase and the inducible cyclooxygenase COX-2 expression
      using immunocytochemistry in tumors of a series of patients with advanced breast
      cancer treated with aromatase inhibitors. Aromatase was expressed in 58/102
      breast cancers. This is similar to the percentage previously reported for
      aromatase activity. Interestingly, aromatase was expressed in a variety of cell
      types, including tumor, stromal, adipose, and endothelial cells. Since
      prostaglandin E2 is known to regulate aromatase gene expression and is the
      product of COX-2, an enzyme frequently overexpressed in tumors,
      immunocytochemistry was performed on the tissue sections using a polyclonal
      antibody to COX-2. Aromatase was strongly correlated (P<0.001) with COX-2
      expression. These results suggest that PGE2 produced by COX-2 in the tumor may be
      important in stimulating estrogen synthesis in the tumor and surrounding tissue.
      No correlation was observed between aromatase or COX-2 expression and the
      response of the patients to aromatase inhibitor treatment. However, only 13
      patients responded. Nine of these patients were aromatase positive. Although
      similar to responses in other studies, this low response rate to second line
      treatment suggests that tumors of most patients were no longer sensitive to the
      effects of estrogen. Recent clinical studies suggest that greater responses occur
      when aromatase inhibitors are used as first line treatment. In the intratumoral
      aromatase mouse model, expression of aromatase in tumors is highly correlated
      with increased tumor growth. First line treatment with letrozole was effective in
      all animals treated and was more effective than tamoxifen in suppressing tumor
      growth. Letrozole was also effective in tumors failing to respond to tamoxifen,
      consistent with clinical findings. In addition, the duration of response was
      significantly longer with the aromatase inhibitor than with tamoxifen, suggesting
      that aromatase inhibitors may offer better control of tumor growth than this
      antiestrogen.

PMID- 11850205
TI  - Modulation of aromatase expression in human breast tissue.
AB  - Aromatase plays an important role in breast cancer development through its role
      in the synthesis of estrogen. Aromatase expression in breast tissue can be
      regulated by several mechanisms. The major promoter usage for aromatase
      expression in breast tumors (i.e. cAMP-stimulated promoters I.3 and II) is
      different from that in normal breast tissue (i.e. glucocorticoid-stimulated
      promoter I.4). Recent characterization of transcription factors that interact
      with the two important regulatory elements near promoters I.3 and II, i.e. S1 and
      CREaro, helps us better understand the mechanism of the switch of promoter usage
      between normal breast tissue and cancer tissue. It is thought that in normal
      breast tissue, the function of promoters I.3 and II is suppressed through the
      binding of EAR-2, COUP-TFI, and EARgamma to S1, and through the binding of
      Snail/Slug proteins to their binding site that quenchs the CREaro activity. In
      cancer tissue, the expression levels of EAR-2, COUP-TFI, EARgamma, Snail, and
      Slug decrease, and aromatase expression is then up regulated through the binding
      of ERRalpha-1 to S1 and the binding of CREB or related factors to CREaro. Results
      from this and other laboratories reveal that aromatase activity in aromatase
      expressing cells can also be modified by treatment with aromatase inhibitors and
      the antiestrogen ICI 182, 780. While aromatase inhibitors are used to treat
      breast cancer, the treatment has been found to increase the level of aromatase in
      the breast tissue of some patients. The enhancement of aromatase activity by
      aromatase inhibitors is thought to be due to a decrease of aromatase protein
      degradation by enzyme-inhibitor complex formation, up-regulation of the aromatase
      gene transcription through a cAMP-mediated mechanism, and an induction of
      aromatase expression by gonadtropins that are released from the pituitary in
      response to a reduction of estrogen levels in circulation in premenopausal women.
      Antiestrogen ICI 182, 780 has been found to suppress aromatase expression, but
      the mechanism has not yet been determined. In addition, aromatase activity and
      expression can be affected by environmental chemicals. A detailed structure
      function study has revealed that flavones, but not isoflavones, are inhibitors of
      aromatase. It was found that flavones bind to the active site of aromatase in an
      orientation in which their rings-A and -C mimic rings-D and -C of the androgen
      substrate. The modulation of aromatase expression by endocrine disrupting
      chemicals is exemplified by two organochlorine pesticides (i.e. toxaphene and
      chlordane) that have been found to be antagonists of ERRalpha-1 orphan receptor.
      These compounds reduce ERRalpha-1 activity, resulting in a suppression of
      aromatase expression.

PMID- 11850207
TI  - Bone phenotype of the aromatase deficient mouse.
AB  - Estrogens are important for normal bone growth and metabolism. The mechanisms are
      incompletely understood. Thus, we have undertaken characterization of the
      skeletal phenotype of aromatase (ArKO) deficient mice. No abnormalities have been
      noted in skeletal patterning in newborns. Adult ArKO mice show decreased femur
      length and decreased peak Bone Mineral Density (BMD) with accelerated bone loss
      by 7 months of age in females. Magnetic resonance microscopy (MR) and microCT
      (microCT) imaging disclosed decreased cancellous connectivity and reduced
      cancellous bone volume in ArKO females. Bone formation rate (BFR) is increased in
      ArKO females and decreased in ArKO males. Estradiol therapy reverses these
      changes. This anabolic effect of estradiol in the male skeleton is supported by
      18-F- Positron Emission Tomography (PET) imaging, which clearly demonstrates
      decreased spinal uptake, but marked increase after estradiol therapy. Serum IGF-1
      levels are high in young female ArKO mice but low in young ArKO males. The
      reduced BMD in ArKO females, despite the presence of elevated serum IGF 1,
      suggests that other mechanism(s) are operative. There is increased B-cell
      lymphopoiesis in adult female ArKO bone marrow cells. These results show that
      ArKO mice show the effects of estrogen deficiency on bone growth, mass,
      metabolism, microarchitecture and the hematopoietic microenvironment.

PMID- 11850209
TI  - Aromatase in atherosclerotic lesions of human aorta.
AB  - It is well documented that estrogens have atheroprotective effects in humans.
      Peripheral aromatization of circulating androgens has been demonstrated to exert
      estrogenic actions in many human tissues, especially in men and post-menopausal
      women. Recently, production of estrogens mediated by aromatase was detected in
      cultured smooth muscle cells and aortic endothelial cells and it has been
      proposed that this in situ produced estrogen may influence the development of
      atherosclerosis. In this study, we first examined aromatase expression by
      immunohistochemistry in human aortic tissues obtained from 85 autopsy cases (50
      males, 35 females, 49.6 +/- 2.9-year-old) and by mRNA in situ hybridization in 10
      cases. We then semi-quantified the level of aromatase mRNA in aortic tissues of
      12 men and 12 post-menopausal women by reverse transcriptase-polymerase chain
      reaction (RT-PCR) to examine whether or not and in which cell types aromatase was
      expressed. We also studied alternative use of multiple exon 1 of its gene and
      immunolocalization of 17beta-hydroxysteroid dehydrogenase type I (17beta-HSD I),
      which converts estrone produced by aromatase to estradiol, a biologically active
      estrogen. Aromatase immunoreactivity and mRNA hybridization signals and 17beta
      HSD I immunoreactivity were all detected in smooth muscle cell (SMC) of the media
      and thickened intima, especially in SMC adjacent to an atheromatous plaque. The
      levels of aromatase mRNA were significantly higher in female cases than in male
      cases (P<0.05). The amount of aromatase mRNA was significantly higher in the
      specimens with fibroatheroma (P<0.05) than other lesions, and was also
      significantly higher in the cases utilizing 1c (I.3) or 1d (PII) of exon 1, i.e.
      gonadal types than those utilizing 1b (I.4), i.e. fibroblasts type as the
      promoter (P<0.01). These results suggest that estrone and estradiol are produced
      in SMC of the human aortic wall and that their production is mediated by
      aromatase and 17beta-HSD I, respectively. Moreover, it was suggested that
      aromatase overexpression, possibly as a result of alternative splicing, may play
      some roles in the development of atherosclerosis.

PMID- 11850210
TI  - Molecular pharmacology of aromatase and its regulation by endogenous and
      exogenous agents.
AB  - Aromatase (estrogen synthase) is the cytochrome P450 enzyme complex that converts
      C19 androgens to C18 estrogens. Aromatase activity has been demonstrated in
      breast tissue in vitro, and expression of aromatase is highest in or near breast
      tumor sites. Thus, local regulation of aromatase by both endogenous factors as
      well as exogenous medicinal agents will influence the levels of estrogen
      available for breast cancer growth. The prostaglandin E2 (PGE2) increases
      intracellular cAMP levels and stimulates estrogen biosynthesis, and our recent
      studies have shown a strong linear association between CYP19 expression and the
      sum of COX-1 and COX-2 expression in breast cancer specimens. PGE2 can bind to
      four receptor subtypes, EP1-EP4, which are coupled to different intracellular
      signaling pathways. In primary human breast stromal cell cultures, aromatase
      activity was significantly induced by PGE2, dexamethasone, and agonists for the
      EP1 and EP2 receptor subtypes. An EP1 antagonist, SC-19220, inhibited the
      induction of enzyme activity by PGE2 or 17-phenyltrinor-PGE2, an EP1 agonist.
      Sulprostone, an EP3 agonist, did not alter aromatase activity levels.
      Investigations are also underway on the regulation of aromatase by exogenous
      medicinal agents. Selective steroidal and nonsteroidal agents are effective in
      inhibiting breast tissue aromatase. The benzopyranone ring system is a molecular
      scaffold of considerable interest, and this scaffold is found in certain
      flavonoid natural products that have weak aromatase inhibitory activity. Our
      novel synthetic route for benzopyranones utilizes readily available salicylic
      acids and terminal alkynes as starting materials. The synthesis of flavones with
      diversity on the benzopyranone moiety and at the C-2 position occurs with good to
      excellent yields using these reaction conditions, resulting in an initial
      benzopyranone library of thirty compounds exhibiting enhanced and differential
      aromatase inhibition. Current medicinal chemistry efforts focus on diversifying
      the benzopyranone scaffold and utilizing combinatorial chemistry approaches to
      construct small benzopyranone libraries as potential aromatase inhibitors.

PMID- 11850208
TI  - Regulation of aromatase activity in bone-derived cells: possible role of mitogen
      activated protein kinase.
AB  - Fetal human osteoblast-like cells and the THP-1 cell line that differentiates
      into macrophage/osteoblast-like cells in the presence of Vitamin D3 and which
      possesses high aromatase activity, constitute a useful model with which to study
      the regulation of aromatase in bone. We showed that dexamethasone (DEX)-induced
      aromatase activity in the THP-1 cell line is completely suppressed by forskolin
      and by dibutyryl cAMP. We therefore investigated the contribution of mitogen
      activated protein kinase (MAPK) to the regulation of aromatase, because cAMP
      inhibits MAPK in many cells. We examined the role of MAPK on aromatase activity
      using PD98059, a selective inhibitor of MEK-1. PD98059 (100 microM) reduced
      DEX+interleukin (IL)-1beta-induced aromatase activity in human osteoblast-like
      cells by more than 90%, whereas 50% of the aromatase mRNA concentration was
      retained compared with the control incubated with DEX+IL-1beta. PD98059 (50
      microM) reduced the activity of aromatase in THP-1 cells by 80% without
      significantly affecting the mRNA level. These results indicated that MAPK plays
      an important role in aromatase activation at the post-transcriptional level.

PMID- 11850211
TI  - Comparative clinical pharmacology and pharmacokinetic interactions of aromatase
      inhibitors.
AB  - The clinical development of aromatase inhibitors (AIs) has been closely guided by
      clinical pharmacological investigations. During the early phases of development
      studies were focused on dose-related pharmacological effectiveness and
      specificity. More recently attention has been given to the metabolic changes
      which AIs elicit, with particular regard to their potential use in early breast
      cancer and the prophylactic setting. Pharmacological effectiveness has been
      studied with plasma oestrogen assays but primary oestrogens (E1 and E2) are not
      helpful in comparing the third generation inhibitors: anastrozole, letrozole,
      exemestane. All three of these compounds suppress whole body aromatisation by
      >96%. Most recently, we have established that significantly greater inhibition is
      achieved by letrozole than anastrozole at their clinically used dosages. This
      more complete inhibition is paralleled by significantly greater suppression of
      E1S.A broad panel of endocrine investigations has indicated that these compounds
      have essentially complete specificity at their clinical dosages. A minor
      androgenic effect of exemestane is revealed by a significant suppression of sex
      hormone binding globulin (SHBG). Lipid and bone biomarker data are being
      collected in many current studies. A pharmacokinetic interaction has been
      established between letrozole and tamoxifen, whereby reduced circulating levels
      of letrozole are found with combined application. Neither anastrozole nor
      letrozole have any effect on plasma concentrations of tamoxifen when given in
      combination with it.

PMID- 11850212
TI  - Local endocrine effects of aromatase inhibitors within the breast.
AB  - To determine the effects of aromatase inhibitors on oestrogen uptake, in situ
      aromatase activity and endogenous oestrogens in the breast, postmenopausal women
      with large primary ER-rich breast cancers have been treated neoadjuvantly for 3
      months with either letrozole (2.5 or 10mg daily) or anastrozole (1 or 10mg daily)
      or exemestane (25mg daily). Patients were given an infusion of 3H-androstenedione
      and 14C-oestrone for 18h before and at the end of the study period. Blood, tumour
      and non-malignant breast were taken immediately after each infusion; oestrogens
      were extracted and purified. Tumour volume was measured before and during
      treatment at monthly intervals so that endocrinological changes could be related
      to clinical response. Treatment with each of the aromatase inhibitors was
      associated with a profound reduction in peripheral aromatase (as monitored by the
      level of plasma 3H-oestrone). There was no consistent effect on uptake of
      radioactively labelled oestrogen into breast tumours but a tendency for levels to
      increase after treatment in non-malignant breast. Conversely, therapy was
      associated with a marked inhibition of in situ oestrogen synthesis in both tumour
      and non-malignant breast (in occasional tissues, inhibitors appeared to be less
      effective but the effect was not related to clinical or pathological responses).
      Similar decreases were apparent in endogenous levels of oestrone and oestradiol.
      The absence of in situ aromatase activity tended to be associated with lack of
      clinical response to aromatase inhibition but the relationship was not absolute,
      limiting the utility of measurements of tumour aromatase as a predictive indices.
      Ex vivo studies of tissue aromatase indicated that such measurements consistently
      underestimate the inhibitory potential of reversible non-steroidal agents (and
      occasionally paradoxical in vitro increases in aromatase activity were seen with
      treatment). However, in situ assays demonstrate that new aromatase inhibitors
      such as anastrozole, exemestane and letrozole have profound effects on the local
      endocrinology within the postmenopausal breast, these being compatible with the
      clinico-pathological changes which occur with treatment.

PMID- 11850213
TI  - Biological and clinical effects of aromatase inhibitors in neoadjuvant therapy.
AB  - Postmenopausal women with large primary oestrogen receptor-rich (>20 fmol/mg
      protein or 80 histoscore) breast cancers have been treated neoadjuvantly with
      either letrozole (2.5 or 10 mg daily n=12 in each case) or anastrozole (1 or 10mg
      daily n=12 and 11, respectively). Tumour was available for analysis before
      treatment (wedge biopsy) and 3 months later at definitive surgery (wide local
      excision or mastectomy). Clinical response to treatment was assessed by
      sequential measurements of tumour volume based on caliper assessment, ultrasound
      and mammography. Results showed that in these selected groups of patients a
      reduction in tumour volume with treatment was observed in 43 of 47 cases (91%).
      Pathological responses, i.e. clear decrease in tumour cellularity or increased
      fibrosis was evident in 32 cases (68%). Furthermore, there was a decrease with
      therapy in immunohistochemical staining for Ki67 in all tumours. Staining for
      progesterone receptor (PgR) was reduced in all 21 PgR-positive cancers treated
      with letrozole and in 16 of 17 positive cancers treated with anastrozole. These
      effects are at least as great as those seen in a non-randomised group of patients
      treated with tamoxifen over the same time period (additionally tamoxifen
      treatment was often associated with an increase in PgR staining). The results
      suggest that potent specific aromatase inhibitors will be valuable in treating
      hormone-dependent cancers.

PMID- 11850214
TI  - A summary of second-line randomized studies of aromatase inhibitors.
AB  - The new generation of selective aromatase inhibitors (anastrozole, letrozole and
      exemestane) offer a significant efficacy and safety advantage over both older
      agents in this class (aminoglutethimide) and the progestins (megestrol acetate
      (MA)), as second-line treatment for postmenopausal women with advanced hormone
      dependent breast cancer who have failed on tamoxifen therapy. Exemestane, a
      steroidal aromatase inhibitor, has been shown to have activity after failure with
      the non-steroidal aromatase inhibitors, anastrozole and letrozole, and could be
      used as third-line treatment. Although the newer aromatase inhibitors belong to
      the same class and appear, from indirect comparisons, to have similar efficacy
      compared with the older therapies, they have different pharmacokinetic and
      pharmacodynamic profiles, suggesting the potential for clinical differences.
      Compared with exemestane and letrozole, anastrozole shows greater selectivity for
      aromatase, as it lacks any evidence of an effect on adrenal steroidogenesis and
      has no androgenic effects. Therefore, it is clear that these agents should not be
      considered to be similar in all respects. In summary, the introduction of the
      aromatase inhibitors represents a significant step forward in the treatment of
      advanced breast cancer in postmenopausal women. Studies in the adjuvant setting
      will ultimately determine whether the differences in pharmacokinetics and
      phamacodynamics will be of clinical relevance.

PMID- 11850216
TI  - Stepwise estrogen suppression manipulating the estrostat.
AB  - Estrogen suppression is an effective endocrine treatment option in pre- as well
      as postmenopausal breast cancer patients. The fact that it produces clinical
      benefits not only in these two groups of patients that differ significantly with
      respect to plasma estrogen levels but also among patients with very low plasma
      estrogen levels due to previous hypophysectomy, adrenalectomy or treatment with
      first/second generation aromatase inhibitors, suggests estrogen deprivation to
      work independent of pretreatment plasma estrogen levels. Interestingly, in vitro
      studies have revealed MCF-7 cells to respond to estrogen deprivation by
      sensitization, causing maximum estradiol stimulation at a concentration 10(-5) to
      10(-4) the concentration needed in wild-type cells. While results from recent
      phase III studies comparing novel aromatase inhibitors and inactivators to
      conventional therapy have suggested that a more effective hormone ablation may be
      translated into an improved clinical efficacy, the biochemical rationale for lack
      of complete cross-resistance between aromatase inhibitors and inactivators or
      aromatase inhibitors and megestrol acetate remains to be explained.
      Interestingly, patients becoming resistant to estrogen deprivation may still
      respond to estrogens administered in pharmacological doses. Future studies are
      warranted to explore alterations in gene expression and signaling mechanisms in
      response to different therapies in tumor tissue in vivo.

PMID- 11850215
TI  - Adaptive hypersensitivity to estradiol: potential mechanism for secondary
      hormonal responses in breast cancer patients.
AB  - Women with hormone dependent breast cancer initially respond to hormone
      deprivation therapy with tamoxifen or oophorectomy for 12-18 months but later
      relapse. Upon secondary therapy with aromatase inhibitors, patients often
      experience further tumor regression. The mechanisms responsible for secondary
      responses are unknown. We postulated that hormone deprivation induces
      hypersensitivity to estradiol. Evidence of this phenomenon was provided in a
      model system involving MCF-7 cells grown in vitro and in xenografts. To determine
      if the ER transcriptional process is involved in hypersensitivity, we examined
      the effect of estradiol on ER reporter activity, PgR, PS2, and c-myc as markers
      and found no alterations in hypersensitive cells. Next, we examined whether MAP
      kinase may be upregulated in the hypersensitive cells as a reflection of
      increased growth factor secretion or action. Basal MAP kinase activity was
      increased both in vitro and in vivo in hypersensitive cells. Proof of principle
      studies indicated that an increase in MAP kinase activity induced by TGFalpha
      administration caused a two- to three-fold shift to the left in estradiol dose
      response curves in wild type cells. Blockade of MAP kinase with PD98059 returned
      the shifted curve back to baseline. These data suggested that MAP kinase
      overexpression could induce hypersensitivity. To determine why MAP kinase was
      increased, we excluded constitutive receptor activity and growth factor secretion
      by the demonstration that the pure anti-estrogen, ICI 182780, could inhibit MAP
      kinase activation. We also excluded hypersensitivity to estradiol induced growth
      factor secretion, and thus MAP kinase activation, since estradiol stimulated MAP
      kinase at 24, 48, and 72 h at the same concentrations in hypersensitive as in
      wild type cells. Surprisingly, a series of experiments suggested that MAP kinase
      increased in hypersensitive cells as a result of estrogen activation via a non
      genomic pathway. We examined the classical signal pathway in which SHC is
      phosphorylated and binds to SOS and GRB-2 to activate Ras, Raf, and MAP kinase.
      With 5-20 min of exposure, estradiol caused binding of SHC to the estrogen
      receptor, phosphorylation of SHC, binding of GRB-2 to SOS, and activation of MAP
      kinase. All of these affects could be blocked by ICI 182780. Taken together,
      these observations suggest that the cell membrane ER pathway may be responsible
      for upregulation of MAP kinase and hypersensitivity in cells adapted to estradiol
      deprivation.

PMID- 11850217
TI  - Adjuvant trials of aromatase inhibitors: determining the future landscape of
      adjuvant endocrine therapy.
AB  - This review will discuss the role of aromatase inhibitors (AIs) in the adjuvant
      setting, and will summarize major strategies behind individual adjuvant trials
      using aromatase inhibitors. Studies with the third generation AIs including
      anastrozole, letrozole and exemestane, have shown better outcome and improved
      therapeutic ratio over second line hormonal approaches (i.e. progestins or
      aminoglutethimide) and, more recently, over tamoxifen also. These promising
      results have led recently to testing of AIs in the adjuvant setting for
      postmenopausal patients. Most trials now in progress are evaluating the role of
      new AIs versus tamoxifen (T) given x 5 years, which in most institutions is
      currently the standard hormonal adjuvant therapy for breast cancer. Three
      adjuvant approaches are being tested. First is the use of AI+T x 5 years in
      combination versus each agent alone, as reflected in the recently completed ATAC
      trial. Second is a sequential approach T first x 2-3 years followed by AIs x 2-3
      years, or the other way round; and third, T x 5 years followed by AIs for
      additional 5 years (i.e. total duration of adjuvant hormones of 10 years). Many
      patients in the above trials will survive their first cancer. Hence, the non
      oncological outcomes known to be affected by hormones are of rising importance.
      Therefore, the assessment of lipids as surrogates for cardiovascular morbidity,
      and of bone mineral status, as a marker for osteoporosis/bone fractures, is an
      important component of these trials. Also discussed in this review are proposals
      for future studies of AIs with focus on hormone resistance, such as early
      alteration of multiple hormonal agents or their intermittent use, the impact of
      the new generation of SERMs or 'pure' antiestrogens on activity of AIs, and the
      rising importance of AIs interacting with biologicals, cytokines or hormone
      modulators.

PMID- 11850218
TI  - Chemoprevention with aromatase inhibitors--trial strategies.
AB  - Estrogen and its catechol metabolites from both the circulation and synthesized
      within the breast are important in the pathogenesis of breast cancer. Blocking
      estrogen's effects on the breast with selective estrogen receptor modulators
      (SERMS) is an ongoing strategy. Thus, tamoxifen and raloxifene reduce risk as
      monotherapy. Aromatase (estrogen synthetase) inhibitors are a logical alternative
      to SERMS. To date, SERMS have demonstrated reduction only in estrogen
      progesterone receptor positive cancers without reduction in receptor negative
      tumors. By inhibiting the parent estrogens and their catechol metabolites, true
      prevention of cancer initiation might occur and reduction not only in the
      receptor positive but also negative tumors might result. Ongoing adjuvant breast
      cancer trials are exploring aromatase inhibitors as alternatives to tamoxifen, or
      in sequence or in combination with tamoxifen. Relative efficacies including
      reduction in contralateral breast cancer, toxicities and end-organ effects and
      impact on quality of life, are being explored. Data from these trials will help
      to guide future chemoprevention strategies. Proof of principal trials in 'high
      risk' cohorts such as premalignant breast lesions, dense screening mammograms,
      high plasma estradiol levels or increased bone density are already ongoing.
      Issues such as dose, schedule, therapeutic index and mono versus combination
      therapy are important to define.

PMID- 11850219
TI  - Analysis of transcriptional regulation of human breast aromatase by in vitro and
      in vivo studies.
AB  - Aromatase mRNA in normal breast tissues is mainly transcribed from exon 1b (I.4)
      of the gene. However, in breast cancer tissues, it is often transcribed from exon
      1c/1d (I.3/PII). Such a switching from exon 1b to exon 1c/1d has often found
      concomitantly with elevated levels of aromatase mRNA. To elucidate the molecular
      mechanism of a switching of multiple exons 1 and enhanced expression of aromatase
      in the breast tissues, we identified essential elements responsible for
      transcription from exon 1b. Gel shift assays indicated that there are two
      essential elements for transcription from exon 1b between -300 and -500 bp in the
      promoter region. The two unique elements have homologous consensus DNA sequences,
      and competed for binding of the specific nuclear protein with each other. We next
      generated transgenic mouse expressing a reporter gene controlled by multiple
      promoters in the human aromatase gene. The mouse gave tissue-specific expression
      of the reporter gene and tissue-specific utilization of the alternative promoter
      regions. These results show that this transgenic mouse is a good model animal for
      the study of tissue-specific regulation of human aromatase gene.

PMID- 11850220
TI  - The potential role of estrogen in aromatase regulation in the breast.
AB  - Aromatase is expressed in both normal and malignant breast tissues. Aromatase
      activity in the breast varies over a wide range. Our previous studies have
      demonstrated that in situ aromatization contributes to the estrogen content of
      breast tumors to a major extent. Consequently, alterations of aromatase activity
      could serve as a major determinant of tissue estradiol content. However, the
      mechanisms and extent of aromatase regulation in breast tissues have not been
      fully established. We have observed an inverse correlation between tumor
      aromatase activity and estrogen content in nude mice bearing xenografts of MCF-7
      cells transfected with the aromatase gene. To investigate the potential role of
      estrogen in aromatase regulation in the breast, studies were carried out in an in
      vitro model. In this model, MCF-7 cells were cultured long term in estrogen
      deprived medium and called by the acronym, LTED cells. We found that long-term
      estrogen deprivation enhanced aromatase activity by 3-4-fold when compared to the
      wild-type MCF-7 cells. Re-exposure of LTED cells to estrogen reduced aromatase
      activity to the levels of the wild-type MCF-7 cells. We also measured aromatase
      activity in 101 frozen breast carcinoma specimens and compared tumor aromatase
      activities in pre-menopausal patients versus post-menopausal patients and in post
      menopausal patients with or without hormone replacement therapy (HRT). Although
      statistically not significant, there was a trend paralleling that observed in the
      in vitro studies. Aromatase activity was higher in breast cancer tissues from the
      patients with lower circulating estrogen levels. Our data suggest that estrogen
      may be involved in the regulation of aromatase activity in breast tissues.

PMID- 11850221
TI  - Peptide inhibition of cytokine-stimulated aromatase activity in breast tissue
      fibroblasts.
AB  - The cytokine interleukin-6 (IL-6) and its soluble receptor (IL-6sR) can act
      synergistically to stimulate aromatase activity in cultured stromal fibroblasts
      derived from breast tissues. In this study, a 16 amino acid peptide, AROHIB, has
      been used in an attempt to block the ability of IL-6 plus IL-6sR to stimulate
      aromatase activity in stromal fibroblasts. Pre-incubation of cells with AROHIB
      for a 3-h period before the addition of IL-6 and IL-6sR resulted in a marked
      (67%) reduction in the ability of these factors to stimulate aromatase activity.
      AROHIB was found to be rapidly degraded when exposed to MCF-7 breast cancer cells
      or fibroblasts. Analysis by FAB-MS was used to identify the site of peptide
      cleavage. Subsequently, a series of 10 amino acid peptides, DP1-DP4, were
      designed, synthesised and tested for their ability to resist proteolytic
      degradation and to inhibit IL-6 plus IL-6sR-stimulated aromatase activity.
      Peptide DP2, a modified version of the active fragment of AROHIB, had N-acetyl
      and C-amino terminal protection and an internal D-amino acid (instead of L form)
      at the site of proteolytic cleavage. Using cells cultured in the presence of 2%
      stripped foetal calf serum, peptide DP2 resulted in a 74% reduction in cytokine
      stimulated aromatase activity. Under serum-free conditions, peptides DP1-DP3
      showed modest inhibitory properties. Results from this study suggest that it may
      be possible to develop small peptides to inhibit cytokine-stimulated aromatase
      activity in a tissue-specific manner.

PMID- 11850222
TI  - Identification of the regulatory regions of the human aromatase P450 (CYP19) gene
      involved in placenta-specific expression.
AB  - Expression of the human CYP19 gene in placental syncytiotrophoblast, ovarian
      granulosa and luteal cells and adipose stromal cells is regulated by tissue
      specific promoters which lie upstream of unique untranslated first exons. In
      placenta, the majority of CYP19 mRNA transcripts contain 5'-sequences encoded by
      exon I.1 which lies >35 kb upstream of the translation initiation sequence in
      exon II. Mononuclear cytotrophoblasts isolated from midterm human placenta
      spontaneously fuse in culture to form multinucleated syncytiotrophoblast. These
      morphological changes are associated with a marked induction of CYP19 gene
      expression. To functionally define genomic regions required for placenta-specific
      expression, fusion genes containing various amounts of exon I.1 5'-flanking
      sequence linked to the human growth hormone (hGH) structural gene, as reporter,
      were introduced into human trophoblast cells in primary monolayer culture and
      into transgenic mice. Our findings using transfected cells and transgenic mice
      suggest that sequences between -501 and -42 bp upstream of exon I.1 contain a
      positive enhancer element(s) that mediates the actions of trophoblast-specific
      transcription factors, as well as a negative element(s) that binds inhibitory
      transcription factors in other cell types. Our findings from transgenic studies
      further indicate that mouse placenta contains the necessary transcription factors
      required to activate the human CYP19 promoter although mouse placenta does not
      express endogenous aromatase.

PMID- 11850223
TI  - The ovarian phenotype of the aromatase knockout (ArKO) mouse.
AB  - Targeted disruption of exon 9 of the cyp19 gene gives rise to a non-functional
      aromatase enzyme incapable of converting androgens to oestrogens. The aromatase
      knockout (ArKO) mouse is, thus, characterised by a dysfunctional pituitary
      gonadal axis, which manifests in non-detectable levels of oestrogen in serum.
      These mice also exhibit elevated levels of circulating gonadotrophins
      (luteinising hormone (LH) and follicle stimulating hormone (FSH)) and
      testosterone. The ArKO mouse is infertile due to folliculogenic disruption and a
      failure to ovulate. The age-dependent ovarian phenotype revealed a block in
      follicular development at the antral stage and a complete absence of corpora
      lutea. By 21-23 weeks of age haemorrhagic cystic follicles were present and by 1
      year there were abnormal follicles, an absence of secondary and antral follicles
      and atretic primary follicles. Interstitial tissue remodelling was extensive and
      exemplified by an increase in collagen deposition and an influx of macrophages,
      coincident with the loss of follicles. In mice, maintained on a soy-free and,
      thus, phytoestrogen-free diet, the ovarian phenotype was accelerated and
      exacerbated. In conclusion, the ovarian phenotype of the ArKO mouse can be
      attributed to the altered hormonal environment brought about by the absence of
      aromatase and the failure of androgens to be converted to oestrogens in the
      presence of elevated gonadotropins.

PMID- 11850224
TI  - Regulation of aromatase by nuclear receptors.
AB  - We investigated the effects of a nuclear receptor system constituted by retinoid
      X receptor (RXR) and its heterodimer partner on the aromatase activity in a
      cultured MCF-7 human breast cancer cell line and also in human ovarian granulosa
      cells, using each selective ligand for retinoic acid receptor, RAR (TTNPB),
      retinoid X receptor, RXR (LG100268), PPARgamma (troglitazone), and vitamin D3
      receptor (cholecalciferol). In MCF-7 cells, the combined treatment with TTNPB and
      LG100268 caused a dramatic stimulation of the aromatase activity. The combined
      treatment with other ligand and LG100268 had little or no effect on the aromatase
      activity. The increase in the aromatase activity by TTNPB plus LG100268 was
      accompanied by an increase in the P450arom mRNA levels, which was also found to
      be related to the specific usage of promoter 1a of the CYP19 gene. These results
      suggest that a nuclear receptor system constituted by a RAR:RXR heterodimer is
      involved in the regulation of aromatase activity in MCF-7 breast cancer cells. In
      cultured human ovarian granulosa cells obtained from patients who underwent in
      vitro fertilization, troglitazone or LG100268 alone decreased the aromatase
      activity, while the combined treatment caused an even greater reduction in this
      activity. Little effect of other specific ligands for RXR heterodimer partners
      may support the notion that the effects of troglitazone and/or LG100268 in human
      granulosa cells may be mediated through the specific activation of PPARgamma:RXR
      heterodimer system. Since similar manners of effects of several PPARgamma ligands
      and/or LG100268 on the aromatase activity were observed in a newly established
      human ovarian granulosa cancer cell line, KGN, we performed the detailed analysis
      of the mechanisms of these effects using this cell line. As a result, the
      inhibitory effect of aromatase activity by troglitazone plus LG100268 was
      accompanied by the decrease of P450arom mRNA level. Furthermore, the loss of
      P450arom expression was considered to be due to both the decreased transcription
      and rapid degradation of its RNA based on the studies of nuclear run-on assay and
      RNA stability assay. In conclusion, RAR:RXR and PPARgamma:RXR heterodimer nuclear
      receptor systems may be other important modulators of estrogen production in
      human breast cancer cells and ovarian granulosa cells, respectively.

PMID- 11850225
TI  - Tissue-specific expression of the human CYP19 (aromatase) gene in ovary and
      adipose tissue of transgenic mice.
AB  - In humans, the CYP19 (aromatase P450) gene is expressed in a number of tissues,
      including gonads, placenta, adipose tissue, skin and brain. The 5'-untranslated
      regions (UTR) of CYP19 mRNA transcripts in these tissues are encoded by different
      tissue-specific first exons, which are alternatively spliced onto a common site
      just upstream of the start of translation in exon II. In ovary, the 5'-UTR of
      CYP19 transcripts is encoded by exon IIa, which lies just upstream of exon II,
      while in adipose, the 5'-UTR of CYP19 transcripts is encoded by exon I.4, which
      lies >20 kb upstream of exon II. To map genomic sequences required for ovary- and
      adipose-specific CYP19 expression, fusion genes containing 2700, 278 and 43 bp of
      DNA flanking the 5'-end of ovary-specific exon IIa, or 348 bp of 5'- flanking DNA
      and 170 bp of adipose-specific exon I.4 were linked to the human growth hormone
      (hGH) gene, as reporter, and introduced into transgenic mice. We observed that
      CYP19(IIa):hGH fusion genes containing as little as 278 bp of exon IIa 5'
      flanking sequence were expressed at high levels in an ovary-specific manner in
      transgenic mice, while the CYP19(IIa)(-43):hGH fusion gene was not expressed in
      any tissue. These results suggest that sequences between -43 and -278 bp upstream
      of exon IIa mediate ovary-specific CYP19 gene expression. In mice carrying the
      CYP19(I.4)(-348):hGH fusion gene, transgene expression was detected in skin and
      in mammary adipose, but not in any of the other tissues examined. These results
      indicate that genomic elements within -348 and +170bp of adipose-specific exon
      I.4 mediate adipose- and skin-specific CYP19 gene expression. Studies are in
      progress using transgenic mice to further define the response elements that
      mediate ovary and adipose-specific hCYP19 gene expression.

PMID- 11850227
TI  - Faslodex (ICI 182, 780), a novel estrogen receptor downregulator--future
      possibilities in breast cancer.
AB  - Tamoxifen is an effective treatment for breast cancer; however, as well as
      exerting antagonistic effects on the estrogen receptor (ER), tamoxifen acts as a
      partial agonists in estrogen-sensitive tissues, resulting in stimulation of the
      endometrium and tumor growth in some patients who become resistant to
      treatment.ICI 182, 780 (Faslodex), a steroidal estrogen antagonist, is the first
      in a new class of agent-an estrogen receptor downregulator. Pre-clinical breast
      cancer models show that ICI 182, 780 leads to a prolonged duration of response,
      and that it exerts its effects via a different mode of action to tamoxifen. This
      was confirmed in a small clinical study involving 19 post-menopausal advanced
      breast cancer patients, where ICI 182, 780 was highly effective after tamoxifen
      failure. Definitive evidence of the differing modes of action of ICI 182, 780 and
      tamoxifen, were provided in a study involving post-menopausal women with primary
      breast cancer, where analyses of tumor samples following short-term exposure to
      both drugs, showed that ICI 182, 780 reduced tumor ER levels in a dose-dependent
      manner, and to a significantly greater extent than tamoxifen. Additionally,
      unlike tamoxifen, ICI 182, 780 did not promote ER-mediated progesterone receptor
      expression, indicating that it lacks estrogen agonist activity. Ongoing studies
      in post-menopausal women with advanced breast cancer are comparing ICI 182, 780
      to anastrozole and tamoxifen, respectively. Future studies being considered are
      whether ICI 182, 780 may also be effective in breast cancer in pre-menopausal
      women, in early breast cancer and in ductal carcinoma in situ in the breast, in
      combination with other hormonals, cytotoxics and biological modifiers.

PMID- 11850226
TI  - Aromatase expression in male germ cells.
AB  - The cytochrome P450 aromatase (P450arom) is the terminal enzyme responsible for
      the formation of estrogens from androgens. According to the age, aromatase
      activity has been measured in immature and mature rat Leydig cells, as well as in
      Sertoli cells whereas in pig, ram and human the aromatase is mainly present in
      Leydig cells. In the rat testis, we have immunolocalised the P450arom not only in
      Leydig cells but also in germ cells and especially in elongated spermatids.
      Related to the stage of germ cell maturation, we have shown that the level of
      P450arom mRNA transcripts decreases, it is much more abundant in younger than in
      mature germ cells whereas the aromatase activity is two- to four-fold greater in
      spermatozoa when compared to the two other enriched-germ cell preparations.
      Moreover, we have reported the existence of alternative splicing events of
      P450arom mRNA in pachytene spermatocytes and round spermatids giving rise to two
      isoforms lacking the last coding exon which, therefore, cannot encode functional
      aromatase molecules. In rat germ cells, the aromatase gene expression is not only
      under androgen control but also subjected to cytokine (TNFalpha) and growth
      factor (TGFbeta) regulation. In the bank-vole testis, we have evidenced a
      synchronisation between a fully developed spermatogenesis and a strong positive
      immunoreactivity for both P450arom and estrogen receptor (ERbeta) in spermatids.
      Therefore, the aromatase gene expression and its translation in a fully active
      protein in rodent germ cells evidence an additional site for estrogen production
      within the testis. Our recent data showing that human ejaculated spermatozoa
      expressed specific transcripts for P450arom reinforced the observations reported
      in germ cells of other mammalian species. Together with the widespread
      distribution of ERs in testicular cells these data bring enlightenments on the
      hormonal regulation of male reproductive function. Indeed these female hormones
      (or the ratio androgens/estrogens) do play a physiological role (either directly
      on germ cells or via testicular somatic cells) in the maintenance of male gonadal
      functions and obviously, several steps are concerned particularly the spermatid
      production and the epididymal sperm maturation.

PMID- 11850228
TI  - EM-652 (SCH57068), a pure SERM having complete antiestrogenic activity in the
      mammary gland and endometrium.
AB  - In order to minimize the risks of endometrial cancer and the development of
      resistance to antiestrogen therapy, we have synthesized the orally active
      antiestrogen EM-652 which is the most potent of the known antiestrogens and
      exerts pure antiestrogenic activity in the mammary gland and endometrium. EM-652
      inhibits the AF-1 and AF-2 functions of both ERalpha and beta while the
      inhibitory action of OH-TAM is limited to AF-2. EM-652, thus, inhibits Ras
      induced transcriptional activity and blocks SRC-1-stimulated activity of the two
      receptors. The absence of blockade of AF-1 by OH-TAM could explain why resistance
      develops to Tamoxifen treatment. Not only the development, but also the growth of
      established DMBA-induced mammary carcinoma is inhibited by treatment with EM-800,
      the prodrug of EM-652. EM-652 is the most potent antiestrogen to inhibit the
      growth of human breast cancer ZR-75-1, MCF-7 and T-47D cells in vitro. When
      incubated with human Ishikawa endometrial carcinoma cells, EM-800 has no
      stimulatory effect on the estrogen-sensitive parameter alkaline phosphatase
      activity. When administered to ovariectomized animals, EM-800 prevents bone loss,
      and lowers serum cholesterol and triglyceride levels. EM-800 has shown benefits
      in women with breast cancer who had failed Tamoxifen. The above-summarized
      preclinical and clinical data clearly suggest the interest of studying this
      compounds in the neoadjuvant and adjuvant settings and, most importantly, for the
      prevention of breast and uterine cancer.

PMID- 11850229
TI  - Where do selective estrogen receptor modulators (SERMs) and aromatase inhibitors
      (AIs) now fit into breast cancer treatment algorithms?
AB  - The agents used for endocrine therapy in patients with breast cancer have changed
      markedly over the past decade. Tamoxifen remains the anti-oestrogen of choice,
      but could be replaced by the oestrogen receptor down-regulator ICI 182780 or by
      the fixed ring triphenylethylene arzoxifene (previously SERM III) soon. Whilst
      aminoglutethimide and 4-OH androstenedione were the aromatase inhibitors of
      choice, they have been replaced by non-steroidal (anastrozole and letrozole) and
      steroidal (exemestane) inhibitors of high potency and low side effect profile.
      Previously, often used treatments such as progestogens (megestrol acetate and
      medroxyprogesterone acetate) and androgens are now rarely used or confined to
      fourth or fifth line treatments. The LHRH agonist, goserelin, remains the
      treatment of choice for pre-menopausal patients with advanced breast cancer
      although recent randomised trials indicate a response, time to progression and
      survival advantage for the combination of goserelin and tamoxifen compared with
      goserelin alone. The newer treatments have led to questions concerning the
      optimum sequence of agents to use in advanced breast cancer and as neo-adjuvant
      and adjuvant therapy in relation to surgery. Two trials of anastrozole compared
      with tamoxifen and one trial of letrozole compared with tamoxifen indicate that
      the new triazole aromatase inhibitors have a significant advantage over the anti
      oestrogen with respect to time to progression and survival. Similarly, triazole
      aromatase inhibitors give faster and more complete responses compared with
      tamoxifen when used in post-menopausal women before surgery. Major research
      questions remain with respect to the aromatase inhibitors used as adjuvant
      therapy. Anastrozole is being tested alone or in combination with tamoxifen
      compared with tamoxifen in the 'so-called' ATAC trial. Over 9000 patients have
      been randomised to this important study: the results will be available late-2001.
      A similar study comparing letrozole and tamoxifen started recently under the
      auspices of the Breast International Group. Importantly, this trial is also
      comparing the sequence of tamoxifen followed by letrozole (or vice versa). A
      similar trial of exemestane given after 2-3 years of tamoxifen compared with 5
      years of tamoxifen is recruiting well as is a study comparing letrozole (or
      placebo) for 5 years after 5 years of adjuvant tamoxifen. These studies may show
      that aromatase inhibitors are superior to tamoxifen or that a sequence is
      preferable.ICI 182780 causes complete oestrogen receptor down-regulation leading
      to a the lack of agonist activity of the drug. Two trials of ICI 182780 compared
      with anastrozole for advanced disease will report later this year and a
      comparison with tamoxifen next year. Arzoxifene (SERM III) is being tested
      against tamoxifen. These studies are likely to result in new anti-oestrogens
      being introduced into the clinic. Most of our endocrine treatments deprived the
      tumour cell of oestradiol. In vitro experiments with MCF-7 cells indicate that
      tumour cells can adapt and then grow in response to low oestrogen concentrations
      in the tissue--culture medium. Importantly, the cells were shown to apoptose in
      response to high oestrogen concentrations. A recent clinical trial has
      demonstrated a high response rate to stilboestrol given after a median of four
      previous oestrogen depriving endocrine therapies. These data and the newer
      treatments available indicate a need to re-think our general approach to
      endocrine therapy and endocrine prevention.

PMID- 11850230
TI  - 17alpha-methyl testosterone is a competitive inhibitor of aromatase activity in
      Jar choriocarcinoma cells and macrophage-like THP-1 cells in culture.
AB  - 17alpha-methyl testosterone is a synthetic androgen with affinity for the
      androgen receptor. 17alpha-methyl testosterone is used widely as a component of
      hormone replacement therapy. Previous reports have indicated that contrary to
      testosterone, 17alpha-methyl testosterone is not aromatized. However, 17alpha
      methyl testosterone still could affect local estrogen formation by regulating
      aromatase expression or by inhibiting aromatase action. Both possibilities have
      important clinical implications. To evaluate the effect of 17alpha-methyl
      testosterone on the expression and activity of aromatase, we tested the
      choriocarcinoma Jar cell line, a cell line that express high levels of P450
      aromatase, and the macrophage-like THP-1 cells, which express aromatase only
      after undergoing differentiation. We found that in both cell lines, 17alpha
      methyl testosterone inhibits aromatase activity in a dose-related manner. The
      curve of inhibition parallels that of letrozole and gives complete inhibition at
      10(-4) M 17alpha-methyl testosterone, determined by the tritium release assay.
      17alpha-methyl testosterone does not have detectable effects on aromatase RNA and
      protein expression by Jar cells. Undifferentiated THP-1 cells had no aromatase
      activity and showed no effect of 17alpha-methyl testosterone, but differentiated
      THP-1 (macrophage-like) cells had a similar inhibition of aromatase activity by
      17alpha-methyl testosterone to that seen in Jar cells. The Lineweaver-Burke plot
      shows 17alpha-methyl testosterone to be a competitive aromatase inhibitor. Our
      results show for the first time that 17alpha-methyl testosterone acts as an
      aromatase inhibitor. These findings are relevant for understanding the effects of
      17alpha-methyl testosterone as a component of hormone replacement therapy.
      17alpha-methyl testosterone may, as a functional androgen and orally active
      steroidal inhibitor of endogenous estrogen production, also offer special
      possibilities for the prevention/treatment of hormone-sensitive cancers.

PMID- 11850231
TI  - Cytochrome P450 aromatase (CYP19) in the non-human primate brain: distribution,
      regulation, and functional significance.
AB  - In adult male primates, estrogens play a role in both gonadotropin feedback and
      sexual behavior. Inhibition of aromatization in intact male monkeys acutely
      elevates serum levels of luteinizing hormone, an effect mediated, at least
      partially, within the brain. High levels of aromatase (CYP19) are present in the
      monkey brain and regulated by androgens in regions thought to be involved in the
      central regulation of reproduction. Androgens regulate aromatase
      pretranslationally and androgen receptor activation is correlated with the
      induction of aromatase activity. Aromatase and androgen receptor mRNAs display
      both unique and overlapping distributions within the hypothalamus and limbic
      system suggesting that androgens and androgen-derived estrogens regulate
      complimentary and interacting genes within many neural networks. Long-term
      castrated monkeys, like men, exhibit an estrogen-dependent neural deficit that
      could be an underlying cause of the insensitivity to testosterone that develops
      in states of chronic androgen deficiency. Future studies of in situ estrogen
      formation in brain in the primate model are important for understanding the
      importance of aromatase not only for reproduction, but also for neural functions
      such as memory and cognition that appear to be modulated by estrogens.

PMID- 11850232
TI  - Characterization and purification of a protein binding to the cis-acting element
      for brain-specific exon 1 of the mouse aromatase gene.
AB  - The functional differences between male and female brains commit to the existence
      of androgen that the testis secretes during the perinatal period. Androgen exerts
      its action on the brain after conversion to estrogen by brain aromatase. The
      aromatase appears in some neural nuclei such as in the hypothalamus and amygdala,
      and has been indicated to be involved in the expression of sexuality by the
      results of neurobehavioral analyses involving aromatase-knockout mice. We
      analyzed the brain-specific promoter in order to clarify the control mechanism
      for the expression of brain aromatase, which is deeply concerned in the sexual
      differentiation of the brain. The 202bp upstream region of brain-specific exon 1
      contains at least three kinds of cis-acting elements, Arom-Aalpha, -Abeta and -B.
      In particular, the binding activities as to the Abeta sequence show a tissue
      specific pattern. Gel shift analysis revealed that the Abeta binding factor
      recognizes the TTGGCCCCT sequence. Abeta binding activity is detectable at the
      perinatal stage, but is undetectable at the adult stage in the brain.
      Furthermore, a protein which binds to the Abeta sequence was purified from the
      fetal mouse brain. The molecular mass of the Abeta binding protein was estimated
      to be 49kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis.

PMID- 11850233
TI  - Phosphorylation processes mediate rapid changes of brain aromatase activity.
AB  - The enzyme aromatase (also called estrogen synthase) that catalyzes the
      transformation of testosterone (T) into estradiol plays a key limiting role in
      the action of T on many aspects of reproduction. The distribution and regulation
      of aromatase in the quail brain has been studied by radioenzyme assays on
      microdissected brain areas, immunocytochemistry, RT-PCR and in situ
      hybridization. High levels of aromatase activity (AA) characterize the sexually
      dimorphic, steroid-sensitive medial preoptic nucleus (POM), a critical site of T
      action and aromatization for the activation of male sexual behavior. The
      boundaries of the POM are clearly outlined by a dense population of aromatase
      containing cells as visualized by both immunocytochemistry and in situ
      hybridization histochemistry. Aromatase synthesis in the POM is controlled by T
      and its metabolite estradiol, but estradiol receptors alpha (ERalpha) are not
      normally co-localized with aromatase in this brain area. Estradiol receptor beta
      (ERbeta) has been recently cloned in quail and localized in POM but we do not yet
      know whether ERbeta occurs in aromatase cells. It is therefore not known whether
      estrogens regulate aromatase synthesis directly or by affecting different inputs
      to aromatase cells as is the case with the gonadotropin releasing hormone
      neurons. The presence of aromatase in presynaptic boutons suggests that locally
      formed estrogens may exert part of their effects by non-genomic mechanisms at the
      membrane level. Rapid effects of estrogens in the brain that presumably take
      place at the neuronal membrane level have been described in other species. If
      fast transduction mechanisms for estrogen are available at the membrane level,
      this will not necessarily result in rapid changes in brain function if the
      availability of the ligand does not also change rapidly. We demonstrate here that
      AA in hypothalamic homogenates is rapidly down-regulated by exposure to
      conditions that enhance protein phosphorylation (addition of Ca2+, Mg2+, ATP).
      This inhibition is blocked by kinase inhibitors which supports the notion that
      phosphorylation processes are involved. A rapid (within minutes) and reversible
      regulation of AA is also observed in hypothalamic explants incubated in vitro and
      exposed to high Ca2+ levels (K+-induced depolarization, treatment by
      thapsigargin, by kainate, AMPA or NMDA). The local production and availability of
      estrogens in the brain can therefore be rapidly changed by Ca2+ based on
      variation in neurotransmitter activity. Locally-produced estrogens are as a
      consequence available for non-genomic regulation of neuronal physiology in a
      manner more akin to the action of a neuropeptide/neurotransmitter than previously
      thought.

PMID- 11850234
TI  - Expression of the aromatase cytochrome P450 encoding gene in cattle and sheep.
AB  - During this report the tissue-specific expression and promoter usage of the
      aromatase cytochrome P450 encoding gene, Cyp19, are compared between cattle and
      sheep. In addition, data will be presented on the identification of cis-acting
      regulatory sequences located in the bovine placenta-specific promoter 1.1. In
      cattle and sheep Cyp19 is mainly expressed in the foetal placental layer and
      ovarian granulosa cells but also in other organs as brain or testis. Differently
      spliced transcripts of Cyp19 which include an invariable coding region but a
      variable 5'-untranslated region could be detected in tissues of both species.
      However, in contrast to ovary and brain which express homologous transcript
      variants, different transcripts are present in placentae suggesting that also
      different placenta-specific promoter regions are active in cattle and sheep. The
      analysis of the chromatin structure of the main placental promoter 1.1 in
      different bovine tissues revealed that hypomethylation and the occurrence of
      DNaseI hypersensitive sites (HS) within this region are associated with promoter
      activity. Active regulatory elements were identified in reporter gene studies in
      JEG-3 choriocarcinoma cells. The co-localisation of an E-box element within one
      of the placenta-specific HS suggests that this element is important for Cyp19
      expression in the bovine placenta.

PMID- 11850235
TI  - A comparative approach to structure-function studies of mammalian aromatases.
AB  - To date, structure--function studies of aromatase cytochrome P450 (P450arom) have
      been advanced by point mutation analyses utilizing almost exclusively the human
      enzyme, in conjunction with computer-generated models of the three-dimensional
      form of the enzyme based on prokaryotic cytochromes P450. Recent studies have
      identified duplicated isozymes of porcine P450arom, the gonadal and placental
      forms of which appear to differ substantially in substrate utilization and
      inhibitor sensitivity. We present a comparative approach to define regions of
      P450arom responsible for specific functional characteristics using complimentary
      DNAs encoding the porcine isozymes. Constructs encoding the native and chimeric
      porcine and human P450arom enzymes were transiently expressed and activity was
      assessed using the tritiated water assay. Sensitivity to inhibition by the
      imidazole etomidate was investigated, and P450arom expression was assessed by
      immunoblot analysis. All constructs yielded active P450arom, suggesting that
      exchanging entire structural elements does not preclude catalytic function. The
      activity of the gonadal isozyme was shown to be inhibited by etomidate at
      concentrations 185 and 300-fold lower than those required to induce a similar
      inhibition of the placental and human enzymes, respectively. In contrast, there
      was only a two-fold difference in the sensitivity of the gonadal and placental
      isozymes to inhibition by CGS16949A. Analysis of chimeric constructs indicated
      that the sensitivity to etomidate was associated with residues in the B, B' and C
      helices of the gonadal P450arom encompassing only one of six putative substrate
      recognition sites. Additionally, sensitivity to etomidate was not correlated with
      enzyme activity among the chimeric enzymes. Therefore, it appears that residues
      of the porcine gonadal P450arom that are responsible for etomidate binding may be
      distinct from those involved in substrate recognition and metabolism. These data
      support the notion that a comparative approach employing the use of chimeric
      enzymes provides a useful tool in directing point mutational analysis to
      determine residues important in inhibitor and perhaps substrate recognition of
      P450 enzymes such as P450arom. These studies are currently in progress.

PMID- 11850236
TI  - Phylogeny, expression and enzyme activity of zebrafish cyp19 (P450 aromatase)
      genes.
AB  - The cyp19 encodes P450 aromatase, the enzyme catalyzing the conversion of
      estrogens from androgens. Estrogens affect the dimorphic, anatomical, functional
      and behavioral aspects of development of both males and females. In zebrafish,
      two cyp19 genes, cyp19a and cyp19b were found. They are expressed in ovary and
      brain, respectively. Expression of cyp19b can be detected by 11 days post
      fertilization (dpf) by in situ hybridization in the olfactory bulbs, ventral
      telencephalic region and the hypothalamus of the brain in both male and female,
      where it is generally known to be affecting the reproductive function and sexual
      behavior. COS-1 clones permanently expressing the enzymes have been isolated.
      Both aromatase enzymes encoded by these two genes are functional in COS-1 cells
      and they can use androstenedione and testosterone equally efficiently. The
      presence of two functional cyp19 in zebrafish has its evolutionary and
      physiological importance.

PMID- 11850237
TI  - Differential tissue distribution, developmental programming, estrogen regulation
      and promoter characteristics of cyp19 genes in teleost fish.
AB  - Teleost fish are characterized by exceptionally high levels of brain estrogen
      biosynthesis when compared to the brains of other vertebrates or to the ovaries
      of the same fish. Goldfish (Carassius auratus) and zebrafish (Danio rerio) have
      utility as complementary models for understanding the molecular basis and
      functional significance of exaggerated neural estrogen biosynthesis. Multiple
      cytochrome P450 aromatase (P450arom) cDNAs that derive from separate gene loci
      (cyp19a and cyp19b) are differentially expressed in brain (P450aromB>>A) and
      ovary (P450aromA>>B) and have a different developmental program (B>>A) and
      response to estrogen upregulation (B only). As measured by increased P450aromB
      mRNA, a functional estrogen response system is first detected 24-48 h post
      fertilization (hpf), consistent with the onset of estrogen receptor (ER)
      expression (alpha, beta, and gamma). The 5'-flanking region of the cyp19b gene
      has a TATA box, two estrogen response elements (EREs), an ERE half-site (ERE1/2),
      a nerve growth factor inducible-B protein (NGFI-B)/Nur77 responsive element
      (NBRE) binding site, and a sequence identical to the zebrafish GATA-2 gene neural
      specific enhancer. The cyp19a promoter region has TATA and CAAT boxes, a
      steroidogenic factor-1 (SF-1) binding site, and two aryl hydrocarbon receptor
      (AhR)/AhR nuclear translocator factor (ARNT) binding motifs. Both genes have
      multiple potential SRY/SOX binding sites (16 and 8 in cyp19b and cyp19a,
      respectively). Luciferase reporters have basal promoter activity in GH3 cells,
      but differences (a>>b) are opposite to fish pituitary (b>>a). When microinjected
      into fertilized zebrafish eggs, a cyp19b promoter-driven green fluorescent
      protein (GFP) reporter (but not cyp19a) is expressed in neurons of 30-48 hpf
      embryos, most prominently in retinal ganglion cells (RGCs) and their projections
      to optic tectum. Further studies are required to identify functionally relevant
      cis-elements and cellular factors, and to determine the regulatory role of
      estrogen in neurodevelopment.

PMID- 11850238
TI  - Sublethal concentrations of pleurocidin-derived antimicrobial peptides inhibit
      macromolecular synthesis in Escherichia coli.
AB  - Cationic bactericidal peptides are components of natural host defenses against
      infections. While the mode of antibacterial action of cationic peptides remains
      controversial, several targets, including the cytoplasmic membrane and
      macromolecular synthesis, have been identified for peptides acting at high
      concentrations. The present study identified peptide effects at lower, near
      lethal inhibitory concentrations. An amidated hybrid of the flounder pleurocidin
      and the frog dermaseptin (P-Der), two other pleurocidin derivatives, and
      pleurocidin itself were studied. At 2 microg/ml, the MIC, P-Der inhibited
      Escherichia coli growth in a broth dilution assay but did not cause bacterial
      death within 30 min, as estimated by viable count analysis. Consistent with this,
      P-Der demonstrated a weak ability to permeabilize membranes but was able to
      translocate across the lipid bilayer of unilamellar liposomes. Doses of 20
      microg/ml or more reduced bacterial viable counts by about 2 log orders of
      magnitude within 5 min after peptide treatment. Abrupt loss of cell membrane
      potential, observed with a fluorescent dye, dipropylthiacarbocyanine, paralleled
      bacterial death but did not occur at the sublethal, inhibitory concentrations.
      Both lethal and sublethal concentrations of P-Der affected macromolecular
      synthesis within 5 min, as demonstrated by incorporation of [3H]thymidine,
      [3H]uridine, and [3H]histidine, but the effects were qualitatively distinct at
      the two concentrations. Variations of the inhibition pattern described above were
      observed for pleurocidin and two other derivatives. Our results indicate that
      peptides at their lowest inhibitory concentrations may be less capable of
      damaging cell membranes, while they maintain their ability to inhibit
      macromolecular synthesis. Better understanding of the effects of peptides acting
      at their MICs will contribute to the design of new peptides effective at lower,
      less toxic concentrations.

PMID- 11850239
TI  - Molecular evaluation of the plasma membrane proton pump from Aspergillus
      fumigatus.
AB  - The gene encoding the plasma membrane proton pump (H+ -ATPase) of Aspergillus
      fumigatus, PMA1, was characterized from A. fumigatus strain NIH 5233 and clinical
      isolate H11-20. An open reading frame of 3,109 nucleotides with two introns near
      the N terminus predicts a protein consisting of 989 amino acids with a molecular
      mass of approximately 108 kDa. The predicted A. fumigatus enzyme is 89 and 51%
      identical to H+ - ATPases of Aspergillus nidulans and Saccharomyces cerevisiae,
      respectively. The A. fumigatus PMA1 is a typical member of the P-type ATPase
      family that contains 10 predicted transmembrane segments and conserved sequence
      motifs TGES, CSDKTGT, MLTGD, and GDGVN within the catalytic region. The enzyme
      represents 2% of the total plasma membrane protein, and it is characteristically
      inhibited by orthovanadate, with a 50% inhibitory concentration of approximately
      1.8 microM. H+ -ATPases from Aspergillus spp. contain a highly acidic insertion
      region of 60 amino acids between transmembrane segments 2 and 3, which was
      confirmed for the membrane-assembled enzyme with a peptide-derived antibody. An
      increasing A. fumigatus PMA1 copy number confers enhanced growth in low-pH
      medium, consistent with its role as a proton pump. These results provide support
      for the development of the A. fumigatus H+ -ATPase as a potential drug discovery
      target.

PMID- 11850240
TI  - 1H nuclear magnetic resonance study of oxazolidinone binding to bacterial
      ribosomes.
AB  - The oxazolidinones are a novel class of antibiotics that inhibit initiation of
      protein synthesis in bacteria. In order to investigate their novel mechanism of
      action, the interactions of several oxazolidinones with bacterial 70S ribosomes,
      50S subunits, and 30S subunits have been characterized by (1)H nuclear magnetic
      resonance (NMR) line-broadening analyses and transferred nuclear Overhauser
      enhancement (TRNOE) experiments. PNU-177553 and PNU-100592 (eperezolid) and their
      corresponding enantiomers, PNU-184414 and PNU-107112, were studied. The
      dissociation constants were determined to be 94 +/- 44 microM and 195 +/- 40
      microM for PNU-177553 and eperezolid, respectively. There was a approximately 4
      fold decrease in affinity for their corresponding enantiomers. The NMR-derived
      dissociation constants are consistent with their antibacterial activity. PNU
      177553 and eperezolid were found to bind only to the 50S subunit, with similar
      affinity as to the 70S ribosome, and to have no affinity for the 30S subunit.
      Specific binding of PNU-177553 was further confirmed in TRNOE experiments in
      which positive NOEs observed for the small molecule alone were changed to
      negative NOEs in the presence of bacterial 70S ribosomes. The observed NOEs
      indicated that PNU-177553 did not adopt a significantly different conformation
      when bound to the 70S ribosome, compared to the extended conformation that exists
      when free in solution. Since this is likeliest the case for each of the four
      compounds included in this study, the A ring C5 side chain may be positioned in
      the proper orientation for antibacterial activity in PNU-177553 and eperezolid
      but not in their inactive enantiomers.

PMID- 11850241
TI  - Three cefotaximases, CTX-M-9, CTX-M-13, and CTX-M-14, among Enterobacteriaceae in
      the People's Republic of China.
AB  - Of 15 extended-spectrum beta-lactamase (ESBL)-producing isolates of the family
      Enterobacteriaceae collected from the First Municipal People's Hospital of
      Guangzhou, in the southern part of the People's Republic of China, 9 were found
      to produce CTX-M ESBLs, 3 produced SHV-12, and 3 produced both CTX-M and SHV-12.
      Eleven isolates produced either TEM-1B or SHV-11, in addition to an ESBL.
      Nucleotide sequence analysis of the 12 isolates carrying bla(CTX-M) genes
      revealed that they harbored three different bla(CTX-M) genes, bla(CTX-M-9) (5
      isolates), bla(CTX-M-13) (1 isolate), and bla(CTX-M-14) (6 isolates). These genes
      have 98% nucleotide homology with bla(Toho-2). The bla(CTX-M) genes were carried
      on plasmids that ranged in size from 35 to 150 kb. Plasmid fingerprints and
      pulsed-field gel electrophoresis showed the dissemination of the bla(CTX-M) genes
      through transfer of different antibiotic resistance plasmids to different
      bacteria, suggesting that these resistance determinants are highly mobile.
      Insertion sequence ISEcp1, found on the upstream region of these genes, may be
      involved in the translocation of the bla(CTX-M) genes. This is the first report
      of the occurrence of SHV-12 and CTX-M ESBLs in China. The presence of strains
      with these ESBLs shows both the evolution of bla(CTX-M) genes and their
      dissemination among at least three species of the family Enterobacteriaceae,
      Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae, isolated
      within a single hospital. The predominance of CTX-M type enzymes seen in this
      area of China appears to be similar to that seen in South America but is
      different from those seen in Europe and North America, suggesting different
      evolutionary routes and selective pressures. A more comprehensive survey of the
      ESBL types from China is urgently needed.

PMID- 11850242
TI  - Molecular characterization of a novel class 1 integron containing bla(GES-1) and
      a fused product of aac3-Ib/aac6'-Ib' gene cassettes in Pseudomonas aeruginosa.
AB  - As seen by the disk diffusion method, the clinical strain of Pseudomonas
      aeruginosa Pa695, resistant to all extended-spectrum cephalosporins and
      aminoglycosides, exhibited an unusual synergistic effect between ceftazidime and
      imipenem. This isolate produced an extended-spectrum beta-lactamase (ESBL) with a
      pI of 5.8 that appeared to be chromosomally encoded. Cloning experiments revealed
      that this ESBL was encoded by bla(GES-1), previously described in an integron
      from Klebsiella pneumoniae. In P. aeruginosa Pa695, a higher level of resistance
      to ceftazidime than to ticarcillin was observed, and no synergy between the beta
      lactamase inhibitors and extended-spectrum cephalosporins was detected, in
      contrast to the resistance pattern observed in K. pneumoniae. Further sequence
      analysis demonstrated that the bla(GES-1) gene cassette was located in a class 1
      integron, which contained another sequence corresponding to the fused aac3-Ib and
      aac6'-Ib' gene cassettes. The fusion product was functional, as was the product
      of each gene cloned separately: AAC3-I, despite the deletion of the four last
      amino acids, and AAC6', which carried three amino acid changes compared with the
      most homologous sequence. The AAC3-I protein conferred an expected gentamicin and
      fortimicin resistance, and the AAC6', despite the Leu-119-->Ser substitution,
      yielded resistance to kanamycin, tobramycin, and dibekacin, but slightly affected
      netilmicin and amikacin, and had no apparent effect on gentamicin. The fusion
      product conveyed a large profile of resistance, combining the AAC6' activity with
      a higher level of gentamicin resistance without accompanying fortimicin
      resistance.

PMID- 11850243
TI  - Mutant TEM beta-lactamase producing resistance to ceftazidime, ampicillins, and
      beta-lactamase inhibitors.
AB  - A derivative of the TEM-1 beta-lactamase producing clinically significant levels
      of resistance to ceftazidime and beta-lactamase inhibitors in the presence of
      penicillins was generated following five rounds of DNA shuffling and selection.
      This complex mutant enzyme contained three amino acid substitutions including
      those of residues 104 and 276 that are known to produce extended-spectrum
      resistance and, correspondingly, resistance to beta-lactamase inhibitors.
      Although the Glu104Lys substitution by itself produced low levels of ceftazidime
      resistance, additional amino acid replacements in the enzyme with the triple
      mutation resulted in further enhancement of resistance to ceftazidime. Kinetic
      studies of the purified beta-lactamase enzyme with the triple mutation indicated
      enhancement of the catalytic efficiency for turnover (kcat/Km) of ceftazidime.
      The increases in the Ki values of both clavulanic acid and tazobactam for the
      enzyme with the triple mutation were consistent with the observed bacterial
      resistance to the reversibility of beta-lactam resistance with these inhibitors.

PMID- 11850244
TI  - Ribosomal mutations in Streptococcus pneumoniae clinical isolates.
AB  - Eleven clinical isolates of Streptococcus pneumoniae, isolated in Finland during
      1996 to 2000, had an unusual macrolide resistance phenotype. They were resistant
      to macrolides and streptogramin B but susceptible, intermediate, or low-level
      resistant to lincosamides. No acquired macrolide resistance genes were detected
      from the strains. The isolates were found to have mutations in domain V of the
      23S rRNA or ribosomal protein L4. Seven isolates had an A2059C mutation in two to
      four out of the four alleles encoding the 23S rRNA, two isolates had an A2059G
      mutation in two alleles, one isolate had a C2611G mutation in all four alleles,
      and one isolate had a 69GTG71-to-69TPS71 substitution in ribosomal protein L4.

PMID- 11850245
TI  - Identification and minisequencing-based discrimination of SHV beta-lactamases in
      nosocomial infection-associated Klebsiella pneumoniae in Brisbane, Australia.
AB  - Extended-spectrum beta-lactamases (ESBLs) are active against oxyimino
      cephalosporins and monobactams. Twenty-one Klebsiella pneumoniae isolates
      obtained between 1991 and 1995 at the Princess Alexandra Hospital in Brisbane,
      Australia, were subject to amplification and sequencing of the SHV beta-lactamase
      encoding genes. Thirteen strains were phenotypically ESBL positive. Of these, six
      strains carried the blaSHV-2a gene and seven strains carried the blaSHV-12 gene.
      Eight strains were phenotypically ESBL negative. Of these, seven strains carried
      the non-ESBL blaSHV-11 gene and one strain carried the non-ESBL blaSHV-1 gene.
      There was complete correspondence between the ESBL phenotype and the presence or
      absence of an ESBL-encoding gene(s). In addition, it was determined that of the
      13 ESBL-positive strains, at least 4 carried copies of a non-ESBL-encoding gene
      in addition to the blaSHV-2a or blaSHV12 gene. A minisequencing-based assay was
      developed to discriminate the different SHV classes. This technique, termed
      "first-nucleotide change," involves the identification of the base added to a
      primer in a single-nucleotide extension reaction. The assay targeted
      polymorphisms at the first bases of codons 238 and 240 and reliably discriminated
      ESBL-positive strains from ESBL-negative strains and also distinguished strains
      carrying blaSHV-2a from strains carrying blaSHV-12. In addition, this method was
      used to demonstrate an association between the relative copy numbers of blaSHV
      genes in individual strains and the levels of antibiotic resistance.

PMID- 11850246
TI  - Topoisomerase II and IV quinolone resistance-determining regions in
      Stenotrophomonas maltophilia clinical isolates with different levels of quinolone
      susceptibility.
AB  - The quinolone resistance-determining regions (QRDRs) of topoisomerase II and IV
      genes from Stenotrophomonas maltophilia ATCC 13637 were sequenced and compared
      with the corresponding regions of 32 unrelated S. maltophilia clinical strains
      for which ciprofloxacin MICs ranged from 0.1 to 64 microg/ml. GyrA (Leu-55 to Gln
      155, Escherichia coli numbering), GyrB (Met-391 to Phe-513), ParC (Ile-34 to Arg
      124), and ParE (Leu-396 to Leu-567) fragments from strain ATCC 13637 showed high
      degrees of identity to the corresponding regions from the phytopathogen Xylella
      fastidiosa, with the degrees of identity ranging from 85.0 to 93.5%. Lower
      degrees of identity to the corresponding regions from Pseudomonas aeruginosa
      (70.9 to 88.6%) and E. coli (73.0 to 88.6%) were observed. Amino acid changes
      were present in GyrA fragments from 9 of the 32 strains at positions 70, 85, 90,
      103, 112, 113, 119, and 124; but there was no consistent relation to higher
      ciprofloxacin MICs. The absence of changes at positions 83 and 87, commonly
      involved in quinolone resistance in gram-negative bacteria, was unexpected. The
      GyrB sequences were identical in all strains, and only one strain (ciprofloxacin
      MIC, 16 microg/ml) showed a ParC amino acid change (Ser-80-->Arg). In contrast, a
      high frequency (16 of 32 strains) of amino acid replacements was present in ParE.
      The frequencies of alterations at positions 437, 465, 477, and 485 were higher (P
      < 0.05) in strains from cystic fibrosis patients, but these changes were not
      linked with high ciprofloxacin MICs. An efflux phenotype, screened by the
      detection of decreases of at least twofold doubling dilutions of the
      ciprofloxacin MIC in the presence of carbonyl cyanide m-chlorophenylhydrazone
      (0.5 microg/ml) or reserpine (10 microg/ml), was suspected in seven strains.
      These results suggest that topoisomerases II and IV may not be the primary
      targets involved in quinolone resistance in S. maltophilia.

PMID- 11850247
TI  - Evidence of active efflux in resistance to ciprofloxacin and to ethidium bromide
      by Mycoplasma hominis.
AB  - The uptake of fluoroquinolones was characterized for the fluoroquinolone
      susceptible strain PG21 of Mycoplasma hominis. Accumulation of fluoroquinolones
      appeared to occur by passive diffusion. Addition of arginine as the energizer
      significantly reduced the uptake of fluoroquinolones, suggesting the presence of
      an energy-dependent efflux process. Reserpine and orthovanadate, two multidrug
      pump inhibitors, increased significantly the ciprofloxacin (CIP) uptake. In
      contrast, such a strong effect was not observed for moxifloxacin and pefloxacin
      uptakes. Two ethidium bromide (EtBr)-resistant strains, selected in vitro, showed
      a resistance profile compatible with a multidrug-resistant phenotype, with
      increased MICs for the hydrophilic fluoroquinolones, CIP and norfloxacin, EtBr,
      and acriflavine. Taking the EtBr-resistant strain RB1La as a model, a significant
      decrease of the CIP and EtBr uptakes was observed compared to the reference
      strain PG21. In the presence of reserpine and orthovanadate, both inhibitors of
      ATP-dependent efflux pumps, the CIP uptake increased significantly, reaching
      approximately the same level as that of the susceptible strain. Similar results
      were obtained with EtBr uptake and efflux experiments. Our data suggest the
      presence of an active efflux system, possibly an ABC-type efflux pump, implicated
      in the resistance to CIP and unrelated compounds like EtBr in the human
      mycoplasma M. hominis.

PMID- 11850248
TI  - Fluoroquinolone resistance in Streptococcus pneumoniae in United States since
      1994-1995.
AB  - The in vitro activities of ciprofloxacin, levofloxacin, gatifloxacin, and
      moxifloxacin against a large collection of clinical isolates of Streptococcus
      pneumoniae (n = 4,650) obtained over a 5-year period, 1994-1995 through 1999
      2000, were assessed as part of a longitudinal multicenter U.S. surveillance study
      of antimicrobial resistance. Three sampling periods were used during this
      investigation, the winter seasons of 1994-1995, 1997-1998, and 1999-2000; and
      1,523, 1,596 and 1,531 isolates were collected during these three periods,
      respectively. The overall rank order of activity of the four fluoroquinolones
      examined in this study was moxifloxacin > gatifloxacin > levofloxacin =
      ciprofloxacin, in which moxifloxacin (MIC at which 90% of isolates are inhibited
      [MIC(90)], 0.25 microg/ml; modal MIC, 0.12 microg/ml) was twofold more active
      than gatifloxacin (MIC(90), 0.5 microg/ml; modal MIC, 0.25 microg/ml), which in
      turn was fourfold more active than either levofloxacin (MIC(90), 1 microg/ml;
      modal MIC, 1 microg/ml) or ciprofloxacin (MIC(90), 2 microg/ml; modal MIC, 1
      microg/ml). Changes in the in vitro activities of fluoroquinolones against S.
      pneumoniae strains in the United States over the 5-year period of the survey were
      assessed by comparing the MIC frequency distributions of the study drugs against
      the isolates obtained during the three sampling periods encompassing this
      investigation. These comparisons revealed no evidence of changes in the in vitro
      activities of the fluoroquinolones. In addition, the percentages of isolates in
      the three sampling periods for which MICs were above the resistance breakpoints
      were compared. Low percentages of resistant strains were detected, and there was
      no evidence of resistance rate changes over time. For example, by use of a
      ciprofloxacin MIC of > or = 4 microg/ml to define resistance, the proportions of
      isolates from the three sampling periods for which MICs were at or above this
      breakpoint were 1.2, 1.6, and 1.4%, respectively. A total of 164 unique isolates
      (n = 58 from 1994-1995, 65 from 1997-1998, and 42 from 1999-2000) were examined
      for evidence of mutations in the quinolone resistance-determining regions (QRDRs)
      of the parC and the gyrA genes. Forty-nine isolates harbored at least one
      mutation in the QRDRs of one or both genes (1994-1995, n = 15; 1997-1998, n = 19;
      1999-2000, n = 15). Among the 4,650 isolates of S. pneumoniae examined in the
      study, we estimated that 0.3% had mutations in both the parC and gyrA loci. The
      majority of mutations (67.3% of the mutations in 49 isolates with mutations) were
      amino acid substitutions in the parC locus only. Four isolates had a mutation in
      the gyrA locus only, and 12 isolates had mutations in both genes (8.2 and 24.5%
      of isolates with mutations, respectively). There was no significant difference in
      the number of isolates with parC and/or gyrA mutations detected during each study
      period. Finally, because of the magnitude of the study, we had reasonably large
      numbers of pneumococcal isolates with genotypically defined mechanisms of
      fluoroquinolone resistance and were thus able to determine the effects of
      specific resistance mutations on the activities of different fluoroquinolones. In
      general, isolates with mutations in parC only were resistant to ciprofloxacin but
      remained susceptible to levofloxacin, gatifloxacin, and moxifloxacin, whereas
      isolates with mutations in gyrA only and isolates with mutations in both parC and
      gyrA were resistant to all four fluoroquinolones tested.

PMID- 11850249
TI  - Antibacterial properties of dermaseptin S4 derivatives with in vivo activity.
AB  - Derivatives of the cytotoxic peptide dermaseptin S4 have recently emerged as
      potential antimicrobial agents. Here, we report on the antibacterial properties
      of three derivatives with improved toxicity profiles: a 28-residues K4K20-S4 and
      two shorter versions, K4-S4(1-16) and K4-S4(1-13). The range of MICs of K4K20-S4
      against clinical isolates of Staphylococcus aureus, Pseudomonas aeruginosa, and
      Escherichia coli were, respectively, 1 to 4, 1 to 4, and 1 to 16 microg/ml. MICs
      of the short derivatives were rather similar or two to fourfold higher. Each of
      the three peptides was rapidly bactericidal in vitro, reducing the number of
      viable CFU of either E. coli or S. aureus by 6 log units in 30 min or less.
      Compared with MSI-78 or PG-1, K4-S4(1-13) was at least as potent against bacteria
      (assessed at two MIC multiples) but displayed lesser toxicity against human
      erythrocytes. Serial passage in subinhibitory concentrations led to emergence of
      resistance to commercial antibiotics but not to the L- or D isomer of either of
      the dermaseptin derivatives. The short derivatives were further investigated for
      antibacterial activity in vivo, using a peritonitis model of mice infected with
      P. aeruginosa. Naive mice in the vehicle control group exhibited 75% mortality,
      compared to 18 or 36% mortality in mice that received a single intraperitoneal
      injection (4.5 mg/kg) of K4-S4(1-16) or K4-S4(1-13), respectively. In vivo
      bactericidal activity was confirmed in neutropenic mice, where intraperitoneal
      administration of K4-S4(1-16) reduced the number of viable CFU in a dose
      dependent manner by >3 log units within 1 h of exposure, and this was sustained
      for at least 5 h. Overall, the data suggest that dermaseptin S4 derivatives could
      be useful in treatment of infections, including infections caused by multidrug
      resistant bacteria.

PMID- 11850250
TI  - Cytotoxic activities of alkylphosphocholines against clinical isolates of
      Acanthamoeba spp.
AB  - Free-living amoebae of the genus Acanthamoeba are causing serious chronic
      conditions such as destructive keratitis in contact lens wearers or granulomatous
      amoebic encephalitis in individuals with compromised immune systems. Both are
      characterized by the lack of availability of sufficiently effective and
      uncomplicated, manageable treatments. Hexadecylphosphocholine (miltefosine) is
      licensed for use as a topical antineoplastic agent, but it is also active in
      vitro against several protozoan parasites, and it was applied very successfully
      for the treatment of human visceral leishmaniasis. The aim of our study was to
      evaluate the efficacy of hexadecylphosphocholine and other alkylphosphocholines
      (APCs) against Acanthamoeba spp. The in vitro activities of eight different APCs
      against three Acanthamoeba strains of various pathogenicities were determined.
      All substances showed at least amoebostatic effects, and some of them disrupted
      the amoebae, as shown by the release of cytoplasmic enzyme activity.
      Hexadecylphosphocholine exhibited the highest degree of cytotoxicity against
      trophozoites, resulting in complete cell death at a concentration as low as 40
      microM, and also displayed significant cysticidal activity.
      Hexadecylphosphocholine may be a promising new candidate for the topical
      treatment of Acanthamoeba keratitis and, conceivably, even for the oral treatment
      of granulomatous amoebic encephalitis.

PMID- 11850251
TI  - Comparison of fractional inhibitory concentration index with response surface
      modeling for characterization of in vitro interaction of antifungals against
      itraconazole-susceptible and -resistant Aspergillus fumigatus isolates.
AB  - Although the fractional inhibitory concentration (FIC) index is most frequently
      used to define or to describe drug interactions, it has some important
      disadvantages when used for drugs against filamentous fungi. This includes
      observer bias in the determination of the MIC and no agreement on the endpoints
      (MIC-0, MIC-1, or MIC-2 [> or = 95, > or = 75, and > or = 50% growth inhibition,
      respectively]) when studying drug combinations. Furthermore, statistical analysis
      and comparisons are troublesome. The use of a spectrophotometric method to
      determine the effect of drug combinations yields quantitative data and permits
      the use of model fits to the whole response surface. We applied the response
      surface model described by Greco et al. (W. R. Greco, G. Bravo, and J. C.
      Parsons, Pharmacol. Rev. 47:331-385, 1995) to determine the interaction
      coefficient alpha (ICalpha) using a program developed for that purpose and
      compared the results with FIC indices. The susceptibilities of amphotericin B
      (AM), itraconazole (IT), and terbinafine (TB) were tested either alone or in
      combination against 10 IT-susceptible (IT-S) and 5 IT-resistant (IT-R) clinical
      strains of Aspergillus fumigatus using a modified checkerboard microdilution
      method that employs the dye MTT [3-(4,5-dimethyl-2-thiazyl)2,5-diphenyl-2H
      tetrazolium bromide]. Growth in each well was determined by a spectrophotometer.
      FIC indices were determined and ICalpha values were estimated for each organism
      strain combination, and the latter included error estimates. Depending on the MIC
      endpoint used, the FIC index ranged from 1.016 to 2.077 for AM-IT, from 0.544 to
      1.767 for AM-TB, and from 0.656 to 0.740 for IT-TB for the IT-S strains. For the
      IT-R strains the FIC index ranged from 0.308 to 1.767 for AM-IT, from 0.512 to
      1.646 for AM-TB, and from 0.403 to 0.497 for IT-TB. The results indicate that the
      degree of interaction is not only determined by the agents themselves but also by
      the choice of the endpoint. Estimates of the ICalpha values showed more
      consistent results. Although the absolute FIC indices were difficult to
      interpret, there was a good correlation with the results obtained using the
      ICalpha values. The combination of AM with either IT or TB was antagonistic in
      vitro, whereas the combination of IT and TB was synergistic in vitro for both IT
      S and IT-R strains. The use of response surface modeling to determine the
      interaction of drugs against filamentous fungi is promising, and more consistent
      results are obtained by this method than by using FIC indices.

PMID- 11850253
TI  - Assessment of mitochondrial toxicity in human cells treated with tenofovir:
      comparison with other nucleoside reverse transcriptase inhibitors.
AB  - Drug-associated dysfunction of mitochondria is believed to play a role in the
      etiology of the various adverse symptoms that occur in human immunodeficiency
      virus (HIV)-infected patients treated with the nucleoside reverse transcriptase
      inhibitors (NRTIs). Tenofovir, a nucleotide analog recently approved for use in
      the treatment of HIV infection, was evaluated in vitro for its potential to cause
      mitochondrial toxicity and was compared to currently used NRTIs. Treatment with
      tenofovir (3 to 300 microM) for up to 3 weeks produced no significant changes in
      mitochondrial DNA (mtDNA) levels in human hepatoblastoma (HepG2) cells, skeletal
      muscle cells (SkMCs), or renal proximal tubule epithelial cells. The potencies of
      inhibition of mtDNA synthesis by the NRTIs tested were zalcitabine (ddC) >
      didanosine (ddI) > stavudine > zidovudine (ZDV) > lamivudine = abacavir =
      tenofovir, with comparable relative effects in the three cell types. Unlike ddC
      and ddI, tenofovir did not affect cellular expression of COX II and COX IV, two
      components of the mitochondrial cytochrome c oxidase complex. Lactate production
      was elevated by less than 20% in HepG2 cells or SkMCs following treatment with
      300 microM tenofovir. In contrast, lactate synthesis increased by >200% in the
      presence of 300 microM ZDV. Thus, treatment of various human cell types with
      tenofovir at concentrations that greatly exceed those required for it both to
      have in vitro anti-HIV type 1 activity in peripheral blood mononuclear cells (50%
      effective concentration, 0.2 microM) and to achieve therapeutically relevant
      levels in plasma (maximum concentrations in plasma, 0.8 to 1.3 microM) is not
      associated with mitochondrial toxicity.

PMID- 11850252
TI  - Interference between D30N and L90M in selection and development of protease
      inhibitor-resistant human immunodeficiency virus type 1.
AB  - We studied the evolutionary relationships between the two protease inhibitor (PI)
      resistance mutations, D30N and L90M, of human immunodeficiency virus type 1 (HIV
      1). The former is highly specific for nelfinavir resistance, while the latter is
      associated with resistance to several PIs, including nelfinavir. Among patients
      with nelfinavir treatment failure, we found that D30N acquisition was strongly
      suppressed when L90M preexisted. Thus, D30N/L90M double mutations not only were
      detected in a very limited number of patients but also accounted for a minor
      fraction within each patient. In the disease course, the D30N and L90M clones
      readily evolved independently of each other, and later the D30N/L90M double
      mutants emerged. The double mutants appeared to originate from the D30N lineage
      but not from the L90M lineage, or were strongly associated with the former.
      However, their evolutionary pathways appeared to be highly complex and to still
      have something in common, as they always contained several additional
      polymorphisms, including L63P and N88D, as common signatures. These results
      suggest that D30N and L90M are mutually exclusive during the evolutionary
      process. Supporting this notion, the D30N/L90M mutation was also quite rare in a
      large clinical database. Recombinant viruses with the relevant mutations were
      generated and compared for the ability to process p55gag and p160pol precursor
      proteins as well as for their infectivity. L90M caused little impairment of the
      cleavage activities, but D30N was detrimental, although significant residual
      activity was observed. In contrast, D30N/L90M demonstrated severe impairment.
      Thus, the concept of mutual antagonism of the two mutations was substantiated
      biochemically and functionally.

PMID- 11850254
TI  - Broad-spectrum antiherpes activities of 4-hydroxyquinoline carboxamides, a novel
      class of herpesvirus polymerase inhibitors.
AB  - Through broad screening of the compound library at Pharmacia, a naphthalene
      carboxamide was identified as a nonnucleoside inhibitor of human cytomegalovirus
      (HCMV) polymerase. Structure-activity relationship studies demonstrated that a
      quinoline ring could be substituted for naphthalene, resulting in the discovery
      of a 4-hydroxyquinoline-3-carboxamide (4-HQC) class of antiviral agents with
      unique biological properties. In vitro assays with the 4-HQCs have demonstrated
      potent inhibition of HCMV, herpes simplex virus type 1 (HSV-1), and varicella
      zoster virus (VZV) polymerases but no inhibition of human alpha, delta, and gamma
      polymerases. Antiviral cell culture assays have further confirmed that these
      compounds are active against HCMV, HSV-1, HSV-2, VZV, and many animal
      herpesviruses. However, these compounds were not active against several
      nonherpesviruses representing different DNA and RNA virus families. A strong
      correlation between the viral DNA polymerase and antiviral activity for this
      class of compounds supports inhibition of the viral polymerase as the mechanism
      of antiviral activity. Northern blot analysis of immediate-early and late viral
      transcripts also pointed to a block in the viral life cycle consistent with
      inhibition of viral DNA replication. In vitro HCMV polymerase assays indicate
      that the 4-HQCs are competitive inhibitors of nucleoside binding. However, no
      cross-resistance could be detected with ganciclovir-resistant HCMV or acyclovir
      resistant HSV-1 mutants. The unique, broad-spectrum activities of the 4-HQCs may
      offer new opportunities for treating many of the diseases caused by
      herpesviruses.

PMID- 11850255
TI  - Emergence of resistance to protease inhibitor amprenavir in human
      immunodeficiency virus type 1-infected patients: selection of four alternative
      viral protease genotypes and influence of viral susceptibility to coadministered
      reverse transcriptase nucleoside inhibitors.
AB  - Previous data have indicated that the development of resistance to amprenavir, an
      inhibitor of the human immunodeficiency virus type 1 protease, is associated with
      the substitution of valine for isoleucine at residue 50 (I50V) in the viral
      protease. We present further findings from retrospective genotypic and phenotypic
      analyses of plasma samples from protease inhibitor-naive and nucleoside reverse
      transcriptase inhibitor (NRTI)-experienced patients who experienced virological
      failure while participating in a clinical trial where they had been randomized to
      receive either amprenavir or indinavir in combination with NRTIs. Paired baseline
      and on-therapy isolates from 31 of 48 (65%) amprenavir-treated patients analyzed
      demonstrated the selection of protease mutations. These mutations fell into four
      distinct categories, characterized by the presence of either I50V, I54L/I54M,
      I84V, or V32I+I47V and often included accessory mutations, commonly M46I/L. The
      I50V and I84V genotypes displayed the greatest reductions in susceptibility to
      amprenavir, although each of the amprenavir-selected genotypes conferred little
      or no cross-resistance to other protease inhibitors. There was a significant
      association, for both amprenavir and indinavir, between preexisting baseline
      resistance to NRTIs subsequently received during the study and development of
      protease mutations (P = 0.014 and P = 0.031, respectively). Our data provide a
      comprehensive analysis of the mechanisms by which amprenavir resistance develops
      during clinical use and present evidence that resistance to concomitant agents in
      the treatment regimen predisposes to the development of mutations associated with
      protease inhibitor resistance and treatment failure.

PMID- 11850256
TI  - Single- and multiple-dose pharmacokinetics of caspofungin in healthy men.
AB  - Caspofungin, a glucan synthesis inhibitor, is being developed as a parenteral
      antifungal agent. The pharmacokinetics of caspofungin following 1-h intravenous
      infusions in healthy men was investigated in four phase I studies. In an
      alternating two-panel (six men each), rising-single-dose study, plasma drug
      concentrations increased proportionally with the dose following infusions of 5 to
      100 mg. The beta-phase half-life was 9 to 10 h. The plasma drug clearance rate
      averaged 10 to 12 ml/min. Renal clearance of unchanged drug was a minor pathway
      of elimination (approximately 2% of the dose). Multiple-dose pharmacokinetics
      were investigated in a 2-week, serial-panel (5 or 6 men per panel) study of doses
      of 15, 35, and 70 mg administered daily; a 3-week, single-panel (10 men) study of
      a dose of 70 mg administered daily; and a parallel panel study (8 men) of a dose
      of 50 mg administered daily with or without a 70-mg loading dose on day 1.
      Moderate accumulation was observed with daily dosing. The degree of drug
      accumulation and the time to steady state were somewhat dose dependent.
      Accumulation averaged 24% at 15 mg daily and approximately 50% at 50 and 70 mg
      daily. Mean plasma drug concentrations were maintained above 1.0 microg/ml, a
      target selected to exceed the MIC at which 90% of the isolates of the most
      clinically relevant species of Candida were inhibited, throughout therapy with
      daily treatments of 70 or 50 mg plus the loading dose, while they fell below the
      target for the first 2 days of a daily treatment of 50 mg without the loading
      dose. Caspofungin infused intravenously as a single dose or as multiple doses was
      generally well tolerated. In conclusion, the pharmacokinetics of caspofungin
      supports the clinical evaluation of once-daily dosing regimens for efficacy
      against fungal infections.

PMID- 11850257
TI  - Pharmacokinetic modeling and simulations of interaction of amprenavir and
      ritonavir.
AB  - Data from three pharmacokinetic drug interaction studies of amprenavir and
      ritonavir were used to develop a pharmacokinetic interaction model using NONMEM
      (nonlinear mixed-effect model). A two-compartment linear model with first-order
      absorption best fit the amprenavir data, while a one-compartment model was used
      to describe the ritonavir data. The inhibition of elimination of amprenavir by
      ritonavir was modeled with a maximum effect (Emax) inhibition model and the
      observed ritonavir concentration. Monte Carlo simulation was then used to predict
      amprenavir concentrations for various combinations of amprenavir and ritonavir in
      twice-daily and once-daily dosing regimens. Simulated minimum amprenavir
      concentrations in plasma (Cmin) in twice-daily and once-daily dosing regimens
      were compared with protein binding-adjusted 50% inhibitory concentrations (IC50s)
      for clinical human immunodeficiency virus isolates with different
      susceptibilities to protease inhibitors (central tendency ratios). The model
      based on the first two studies predicted the results of the third study. Data
      from all three studies were then combined to refine the final model. The observed
      and simulated noncompartmental pharmacokinetic parameters agreed well. From this
      model, several candidate drug regimens were simulated. These simulations suggest
      that, in patients who have clinically failed a traditional amprenavir regimen, a
      regimen of 600 mg of amprenavir with 100 mg of ritonavir twice daily would result
      in Cmin-to-IC50 ratios similar to that of 1,200 mg of amprenavir twice daily
      alone for wild-type viruses. In addition, once-daily regimens that result in
      C(min)s above the protein binding-corrected IC50s for wild-type virus are clearly
      feasible.

PMID- 11850258
TI  - Doxycycline induces expression of P glycoprotein in MCF-7 breast carcinoma cells.
AB  - P-glycoprotein (P-gp) overexpression by tumor cells imparts resistance to
      multiple antineoplastic chemotherapeutic agents (multiple drug resistance).
      Treatment of tumor cells with chemotherapeutic agents such as anthracyclines,
      epipodophyllotoxins, and Vinca alkaloids results in induction of P-gp expression.
      This study was performed to determine if clinically relevant antimicrobial drugs
      (i.e., drugs that are used to treat bacterial infections in cancer patients)
      other than antineoplastic agents can induce expression of P-gp in MCF-7 breast
      carcinoma cells. Expression of P-gp and MDR1 mRNA was determined in samples from
      MCF-7 cells that were treated in culture with doxorubicin (positive control) and
      the antimicrobial drugs doxycycline, piperacillin, and cefoperazone. The
      functional status of P-gp was assessed using laser cytometry to determine
      intracellular doxorubicin concentrations. The MTT (3-[4,5-dimethylthiazol-2-yl]
      2,5-diphenyltetrazolium bromide) assay was used to determine if the cytotoxicity
      of experimental drugs was related to their ability to induce P-gp expression. MCF
      7 cells treated with doxycycline (MCF-7/doxy) were stimulated to overexpress P
      gp, whereas cells treated with piperacillin and cefoperazone did not overexpress
      P-gp. MCF-7/doxy cells were compared to a positive-control subline, MCF-7/Adr,
      previously selected for doxorubicin resistance, and to MCF-7 cells treated with
      doxorubicin (MCF-7/doxo). All three sublines overexpressed P-gp and MDR1 mRNA and
      accumulated less intracellular doxorubicin than did control MCF-7 cells. P-gp
      expression was induced only by experimental drugs that were cytotoxic
      (doxorubicin and doxycycline). Doxycycline, a drug that has been used for
      treatment of bacterial infections in cancer patients, can induce functional P-gp
      expression in cancer cells, resulting in multidrug resistance.

PMID- 11850259
TI  - Susceptibilities of herpes simplex viruses to penciclovir and acyclovir in eight
      cell lines.
AB  - The commonly used antiviral drugs acyclovir (ACV) and penciclovir (PCV) possess
      similarly potent antiviral activities in vivo against herpes simplex virus (HSV).
      Assay methods for sensitivity to ACV are not necessarily transferable to PCV,
      even though the two drugs have similar in vivo potencies and mechanisms of
      action. We determined by plaque reduction assay the relative activities of ACV
      and PCV against five laboratory-adapted strains of HSV types 1 and 2 (including
      sensitive and resistant strains) in seven human cell lines and one nonhuman
      primate cell line. Seven characteristics were used to evaluate the cell lines.
      All cell lines were similar in their plating efficiencies and abilities to
      discriminate between sensitive and resistant HSV isolates. Vero and MRC-5 cells
      yielded the most discordant 50% inhibitory concentrations (IC50s) for the two HSV
      types, while Vero and WI-38 VA-13 cells yielded large differences in the IC50s of
      ACV and PCV. The limited life spans and poor plaque morphologies of the
      fibroblast lines were undesirable characteristics. Among the transformed cell
      lines producing well-defined plaques, A549 cells provided the best concordance
      between IC50s for the two HSV types and two antiherpes drugs. Comparison
      experiments with a yield reduction format indicated that the use of assays of
      this type might allow some of the cell-specific properties observed in plaque
      reduction assays to be avoided.

PMID- 11850260
TI  - Mutations in ponA, the gene encoding penicillin-binding protein 1, and a novel
      locus, penC, are required for high-level chromosomally mediated penicillin
      resistance in Neisseria gonorrhoeae.
AB  - Chromosomally mediated penicillin resistance in Neisseria gonorrhoeae occurs in
      part through alterations in penicillin-binding proteins (PBPs) and a decrease in
      outer membrane permeability. However, the genetic and molecular mechanisms of
      transformation of a penicillin-susceptible strain of N. gonorrhoeae to high-level
      penicillin resistance have not been clearly elucidated. Previous studies
      suggested that alterations in PBP 1 were involved in high-level penicillin
      resistance. In this study, we identified a single amino acid mutation in PBP 1
      located 40 amino acids N terminal to the active-site serine residue that was
      present in all chromosomally mediated resistant N. gonorrhoeae (CMRNG) strains
      for which MICs of penicillin were > or = 1 microg/ml. PBP 1 harboring this point
      mutation (PBP 1*) had a three- to fourfold lower rate of acylation (k2/K') than
      wild-type PBP 1 with a variety of beta-lactam antibiotics. Consistent with its
      involvement in high-level penicillin resistance, replacement of the altered ponA
      gene (ponA1) in several CMRNG strains with the wild-type ponA gene resulted in a
      twofold decrease in the MICs of penicillin. Surprisingly, transformation of an
      intermediate-level penicillin-resistant strain (PR100; FA19 penA4 mtr penB5) with
      the ponA1 gene did not increase the MIC of penicillin for this strain. However,
      we identified an additional resistance locus, termed penC, which was required
      along with ponA1 to increase penicillin resistance of PR100 to a high level (MIC
      = 4 microg/ml). The penC locus by itself, when present in PR100, increases the
      MICs of penicillin and tetracycline twofold each. These data indicate that an
      additional locus, penC, is required along with ponA1 to achieve high-level
      penicillin resistance.

PMID- 11850262
TI  - Comparison of in vitro activities of ABT-773 and telithromycin against macrolide
      susceptible and -resistant streptococci and staphylococci.
AB  - The activity of a new ketolide, ABT-773, was compared to the activity of the
      ketolide telithromycin (HMR-3647) against over 600 gram-positive clinical
      isolates, including 356 Streptococcus pneumoniae, 167 Staphylococcus aureus, and
      136 Streptococcus pyogenes isolates. Macrolide-susceptible isolates as well as
      macrolide-resistant isolates with ribosomal methylase (Erm), macrolide efflux
      (Mef), and ribosomal mutations were tested using the NCCLS reference broth
      microdilution method. Both compounds were extremely active against macrolide
      susceptible isolates, with the minimum inhibitory concentrations at which 90% of
      the isolates tested were inhibited (MIC90s) for susceptible streptococci and
      staphylococci ranging from 0.002 to 0.03 microg/ml for ABT-773 and 0.008 to 0.06
      microg/ml for telithromycin. ABT-773 had increased activities against macrolide
      resistant S. pneumoniae (Erm MIC90, 0.015 microg/ml; Mef MIC90, 0.12 microg/ml)
      compared to those of telithromycin (Erm MIC90, 0.12 microg/ml; Mef MIC90, 1
      microg/ml). Both compounds were active against strains with rRNA or ribosomal
      protein mutations (MIC90, 0.12 microg/ml). ABT-773 was also more active against
      macrolide-resistant S. pyogenes (ABT-773 Erm MIC90, 0.5 microg/ml; ABT-773 Mef
      MIC90, 0.12 microg/ml; telithromycin Erm MIC90, >8 microg/ml; telithromycin Mef
      MIC90, 1.0 microg/ml). Both compounds lacked activity against constitutive
      macrolide-resistant Staphylococcus aureus but had good activities against
      inducibly resistant Staphylococcus aureus (ABT-773 MIC90, 0.06 microg/ml;
      telithromycin MIC90, 0.5 microg/ml). ABT-773 has superior activity against
      macrolide-resistant streptococci compared to that of telithromycin.

PMID- 11850261
TI  - Oral artesunate dose-response relationship in acute falciparum malaria.
AB  - The combination of an oral artemisinin derivative (usually artesunate) and
      mefloquine has become standard treatment for multidrug-resistant falciparum
      malaria in several parts of Southeast Asia. The doses of artesunate used in
      monotherapy and combination treatment have largely been derived empirically. In
      order to characterize the in vivo dose-response relationship for artesunate and
      thus rationalize dosing, 47 adult patients with acute uncomplicated falciparum
      malaria and parasitemia > or = 1% were randomized to receive a single oral dose
      of artesunate varying between 0 and 250 mg together with a curative dose of oral
      mefloquine. Acceleration of parasite clearance was used as the pharmacodynamic
      variable. An inhibitory sigmoidal maximum effect (Emax) pharmacodynamic model
      typical of a dose-response curve was fitted to the relationship between dose and
      shortening of parasite clearance time (PCT). The Emax was estimated as 28.6 oral
      h, and the 50% effective concentration was 1.6 mg/kg of body weight. These
      results imply that there is no reduction in PCTs with the use of single doses of
      artesunate higher than 2 mg/kg, and this therefore reflects the average lower
      limit of the maximally effective dose.

PMID- 11850265
TI  - Expression of efflux pump gene pmrA in fluoroquinolone-resistant and -susceptible
      clinical isolates of Streptococcus pneumoniae.
AB  - Thirty-four ciprofloxacin-resistant (MIC > or = 2 microg/ml) and 12 ciprofloxacin
      susceptible clinical isolates of Streptococcus pneumoniae were divided into four
      groups based upon susceptibility to norfloxacin and the effect of reserpine (20
      microg/ml). The quinolone-resistance-determining regions of parC, parE, gyrA, and
      gyrB of all ciprofloxacin-resistant clinical isolates were sequenced, and the
      activities of eight other fluoroquinolones, acriflavine, ethidium bromide,
      chloramphenicol, and tetracycline in the presence and absence of reserpine were
      determined. Despite a marked effect of reserpine upon the activity of
      norfloxacin, there were only a few isolates for which the activity of another
      fluoroquinolone was enhanced by reserpine. For most isolates the MICs of
      acriflavine and ethidium bromide were lowered in the presence of reserpine
      despite the lack of effect of this efflux pump inhibitor on fluoroquinolone
      activity. The strains that were most resistant to the fluoroquinolones were
      predominantly those with mutations in three genes. Expression of the gene
      encoding the efflux pump PmrA was examined by Northern blotting (quantified by
      quantitative competitive reverse transcriptase PCR) and compared with that of S.
      pneumoniae R6 and R6N. Within each group there were isolates that had high-,
      medium-, and low-level expression of this gene; however, increased expression was
      not exclusively associated with those isolates with a phenotype suggestive of an
      efflux mutant. These data suggest that there is another reserpine-sensitive
      efflux pump in S. pneumoniae that extrudes ethidium bromide and acriflavine but
      not fluoroquinolones.

PMID- 11850264
TI  - Antileishmanial activities of several classes of aromatic dications.
AB  - Aromatic dicationic molecules possess impressive activity against a broad
      spectrum of microbial pathogens, including Pneumocystis carinii, Cryptosporidium
      parvum, and Candida albicans. In this work, 58 aromatic cations were examined for
      inhibitory activity against axenic amastigote-like Leishmania donovani parasites.
      In general, the most potent of the compounds were substituted diphenyl furan and
      thiophene dications. 2,5-Bis-(4-amidinophenyl)thiophene was the most active
      compound. This agent displayed a 50% inhibitory concentration (IC50) of 0.42 +/-
      0.08 microM against L. donovani and an in vitro antileishmanial potency 6.2-fold
      greater than that of the clinical antileishmanial dication pentamidine and was
      155-fold more toxic to the parasites than to a mouse macrophage cell line. 2,4
      Bis-(4-amidinopheny)furan was twice as active as pentamidine (IC50), 1.30 +/-
      0.21 microM), while 2,5-bis-(4-amidinopheny)furan and pentamidine were
      essentially equipotent in our in vitro antileishmanial assay. Carbazoles,
      dibenzofurans, dibenzothiophenes, and benzimidazoles containing amidine or
      substituted amidine groups were generally less active than the diphenyl furans
      and thiophenes. In all cases, aromatic dications possessing strong
      antileishmanial activity were severalfold more toxic to the parasites than to a
      cultured mouse macrophage cell line. These structure-activity relationships
      demonstrate the potent antileishmanial activity of several aromatic dications and
      provide valuable information for the future design and synthesis of more potent
      antiparasitic agents.

PMID- 11850263
TI  - Relationship between chloroquine toxicity and iron acquisition in Saccharomyces
      cerevisiae.
AB  - Chloroquine is one of the most effective antimalarials, but resistance to it is
      becoming widespread. However, we do not fully understand either the drug's mode
      of action or the mechanism of resistance. In an effort to expand our
      understanding of the mechanism of action and resistance associated with
      chloroquine, we used Saccharomyces cerevisiae as a model eukaryotic system. To
      aid in the discovery of potential drug targets we applied the transcriptional
      profiling method to identify genes transcriptionally responsive to chloroquine
      treatment in S. cerevisiae. Among the genes that were differentially expressed
      with chloroquine treatment were a number of metal transporters involved in iron
      acquisition (SIT1, ARN2, ARN4, and SMF2). These genes exhibit similar expression
      patterns, and several are known to be regulated by AFT1, a DNA binding protein,
      which responds to iron levels in the cell. We investigated the role of
      chloroquine in iron metabolism by using a variety of approaches, including
      pharmacological, genetic, and biochemical techniques. For these experiments, we
      utilized yeast lacking the major iron uptake pathways (FET3 and FET4) and yeast
      deficient in SIT1, encoding the major up-regulated iron siderophore transporter.
      Our experiments show that yeast genetically or environmentally limited in iron
      availability has increased sensitivity to chloroquine in pharmacological assays
      and that the addition of iron rescues these cells from chloroquine killing.
      55FeCl3 accumulation was inhibited in the presence of chloroquine, and kinetic
      analysis demonstrated that inhibition was competitive. These results are
      consistent with deprivation of iron as a mechanism of chloroquine killing in
      yeast.

PMID- 11850266
TI  - Accumulation of 10 fluoroquinolones by wild-type or efflux mutant Streptococcus
      pneumoniae.
AB  - A method for measuring fluoroquinolone accumulation by Streptococcus pneumoniae
      was rigorously examined. The accumulation of ciprofloxacin, clinafloxacin,
      gatifloxacin, grepafloxacin, levofloxacin, moxifloxacin, norfloxacin, ofloxacin,
      sitafloxacin, and trovafloxacin in the presence and absence of either carbonyl
      cyanide m-chlorophenyl-hydrazone (CCCP) or reserpine was determined for two wild
      type fluoroquinolone-susceptible capsulated S. pneumoniae strains (M3 and M4) and
      the noncapsulated strain R6. Two efflux mutants, R6N (which overexpresses PmrA)
      and a mutant of M4, M22 (no expression of PmrA), were also examined. Essentially,
      the fluoroquinolones fell into two groups. (i) One group consisting of
      ciprofloxacin, grepafloxacin, and norfloxacin accumulated to 72 to 92 ng/mg (dry
      weight) of cells in all strains. (ii) The remainder of the agents accumulated to
      3 to 30 ng/mg (dry weight) of cells. With a decrease in hydrophobicity, there was
      a decrease in the concentration accumulated. With an increase in the molecular
      weight of the free form of each agent, there was also a decrease in the
      concentration accumulated. The strains differed in their responses to reserpine
      and CCCP. For the three fluoroquinolone-susceptible strains, only reserpine had a
      significant effect upon accumulation of moxifloxacin and clinafloxacin by M3 and
      showed no effect for the other agents and strains. For M3 and M4, CCCP enhanced
      the concentration of ciprofloxacin and norfloxacin accumulated, whereas for R6,
      the effect was only statistically significant for ofloxacin. Efflux mutant M22
      accumulated less ciprofloxacin, gatifloxacin, and ofloxacin than M4 did. M22
      accumulated more norfloxacin than M4 did. Reserpine and CCCP had variable effects
      as for the other strains. Differences in the accumulation of fluoroquinolones by
      R6 and R6N were highly dependent upon growth phase, and only for norfloxacin was
      there a significant difference between two strains.

PMID- 11850268
TI  - Pharmacokinetics, excretion, and mass balance of liposomal amphotericin B
      (AmBisome) and amphotericin B deoxycholate in humans.
AB  - The pharmacokinetics, excretion, and mass balance of liposomal amphotericin B
      (AmBisome) (liposomal AMB) and the conventional formulation, AMB deoxycholate
      (AMB-DOC), were compared in a phase IV, open-label, parallel study in healthy
      volunteers. After a single 2-h infusion of 2 mg of liposomal AMB/kg of body
      weight or 0.6 mg of AMB-DOC/kg, plasma, urine, and feces were collected for 168
      h. The concentrations of AMB were determined by liquid chromatography tandem mass
      spectrometry (plasma, urine, feces) or high-performance liquid chromatography
      (HPLC) (plasma). Infusion-related side effects similar to those reported in
      patients, including nausea and back pain, were observed in both groups. Both
      formulations had triphasic plasma profiles with long terminal half-lives
      (liposomal AMB, 152 +/- 116 h; AMB-DOC, 127 +/- 30 h), but plasma concentrations
      were higher (P < 0.01) after administration of liposomal AMB (maximum
      concentration of drug in serum [C(max)], 22.9 +/- 10 microg/ml) than those of AMB
      DOC (Cmax, 1.4 +/- 0.2 microg/ml). Liposomal AMB had a central compartment volume
      close to that of plasma (50 +/- 19 ml/kg) and a volume of distribution at steady
      state (Vss) (774 +/- 550 ml/kg) smaller than the Vss of AMB-DOC (1,807 +/- 239
      ml/kg) (P < 0.01). Total clearances were similar (approximately 10 ml hr(-1) kg(
      1)), but renal and fecal clearances of liposomal AMB were 10-fold lower than
      those of AMB-DOC (P < 0.01). Two-thirds of the AMB-DOC was excreted unchanged in
      the urine (20.6%) and feces (42.5%) with >90% accounted for in mass balance
      calculations at 1 week, suggesting that metabolism plays at most a minor role in
      AMB elimination. In contrast, <10% of the liposomal AMB was excreted unchanged.
      No metabolites were observed by HPLC or mass spectrometry. In comparison to AMB
      DOC, liposomal AMB produced higher plasma exposures and lower volumes of
      distribution and markedly decreased the excretion of unchanged drug in urine and
      feces. Thus, liposomal AMB significantly alters the excretion and mass balance of
      AMB. The ability of liposomes to sequester drugs in circulating liposomes and
      within deep tissue compartments may account for these differences.

PMID- 11850267
TI  - Neurotoxic mode of action of artemisinin.
AB  - We recently described a screening system designed to detect neurotoxicity of
      artemisinin derivatives based on primary neuronal brain stem cell cultures (G.
      Schmuck and R. K. Haynes, Neurotoxicity Res. 2:37-49, 2000). Here, we probe
      possible mechanisms of this brain stem-specific neurodegeneration, in which
      artemisinin-sensitive neuronal brain stem cell cultures are compared with
      nonsensitive cultures (cortical neurons, astrocytes). Effects on the cytoskeleton
      of brain stem cell cultures, but not that of cortical cell cultures, were visible
      after 7 days. However, after a recovery period of 7 days, this effect also became
      visible in cortical cells and more severe in brain stem cell cultures.
      Neurodegeneration appears to be induced by effects on intracellular targets such
      as the cytoskeleton, modulation of the energy status by mitochondrial or
      metabolic defects, oxidative stress or excitotoxic events. Artemisinin reduces
      intracellular ATP levels and the potential of the inner mitochondrial membrane
      below the cytotoxic concentration range in all three cell cultures, with these
      effects being most dominant in the brain stem cultures. Surprisingly, there were
      substantial effects on cortical neurons after 7 days and on astrocytes after 1
      day. Artemisinin additionally induces oxidative stress, as observed as an
      increase of reactive oxygen species and of lipid peroxidation in both neuronal
      cell types. Interestingly, an induction of expression of AOE was only seen in
      astrocytes. Here, manganese superoxide dismutase (MnSOD) expression was increased
      more than 3-fold and catalase expression was increased more than 1.5-fold. In
      brain stem neurons, MnSOD expression was dose dependently decreased. Copper-zinc
      superoxide dismutase and glutathione peroxidase, two other antioxidant enzymes
      that were investigated, did not show any changes in their mRNA expression in all
      three cell types after exposure to artemisinin.

PMID- 11850269
TI  - Plasma protein binding of amphotericin B and pharmacokinetics of bound versus
      unbound amphotericin B after administration of intravenous liposomal amphotericin
      B (AmBisome) and amphotericin B deoxycholate.
AB  - Unilamellar liposomal amphotericin B (AmBisome) (liposomal AMB) reduces the
      toxicity of this antifungal drug. The unique composition of liposomal AMB
      stabilizes the liposomes, producing higher sustained drug levels in plasma and
      reducing renal and hepatic excretion. When liposomes release their drug payload,
      unbound, protein-bound, and liposomal drug pools may exist simultaneously in the
      body. To determine the amounts of drug in these pools, we developed a procedure
      to measure unbound AMB in human plasma by ultrafiltration and then used it to
      characterize AMB binding in vitro and to assess the pharmacokinetics of
      nonliposomal pools of AMB in a phase IV study of liposomal AMB and AMB
      deoxycholate in healthy subjects. We confirmed that AMB is highly bound (>95%) in
      human plasma and showed that both human serum albumin and alpha(1)-acid
      glycoprotein contribute to this binding. AMB binding exhibited an unusual
      concentration dependence in plasma: the percentage of bound drug increased as the
      AMB concentration increased. This was attributed to the low solubility of AMB in
      plasma, which limits the unbound drug concentration to <1 microg/ml. Subjects
      given 2 mg of liposomal AMB/kg of body weight had lower exposures (as measured by
      the maximum concentration of drug in serum and the area under the concentration
      time curve) to both unbound and nonliposomal drug than those receiving 0.6 mg of
      AMB deoxycholate/kg. Most of the AMB in plasma remained liposome associated (97%
      at 4 h, 55% at 168 h) after liposomal AMB administration, so that unbound drug
      concentrations remained at <25 ng/ml in all liposomal AMB-treated subjects.
      Although liposomal AMB markedly reduces the total urinary and fecal recoveries of
      AMB, urinary and fecal clearances based on unbound AMB were similar (94 to 121 ml
      h(-1) kg(-1)) for both formulations. Unbound drug urinary clearances were equal
      to the glomerular filtration rate, and tubular transit rates were <16% of the
      urinary excretion rate, suggesting that net filtration of unbound drug, with
      little secretion or reabsorption, is the mechanism of renal clearance for both
      conventional and liposomal AMB in humans. Unbound drug fecal clearances were also
      similar for the two formulations. Thus, liposomal AMB increases total AMB
      concentrations while decreasing unbound AMB concentrations in plasma as a result
      of sequestration of the drug in long-circulating liposomes.

PMID- 11850270
TI  - RFI-641, a potent respiratory syncytial virus inhibitor.
AB  - Human respiratory syncytial virus (RSV), a paramyxovirus, is a major cause of
      acute upper and lower respiratory tract infections in infants, young children,
      and adults. RFI-641 is a novel anti-RSV agent with potent in vitro and in vivo
      activity. RFI-641 is active against both RSV type A and B strains. The viral
      specificity and the large therapeutic window of RFI-641 (>100-fold) indicate that
      the antiviral activity of the compound is not due to adverse effects on normal
      cells. The potent in vitro activity of RFI-641 can be translated to efficacy in
      vivo: RFI-641 is efficacious when administered prophylactically by the intranasal
      route in mice, cotton rats, and African green monkeys. RFI-641 is also
      efficacious when administered therapeutically (24 h postinfection) in the monkey
      model. Mechanism of action studies indicate that RFI-641 blocks viral F protein
      mediated fusion and cell syncytium formation.

PMID- 11850272
TI  - Risk factors for piperacillin-tazobactam-resistant Pseudomonas aeruginosa among
      hospitalized patients.
AB  - Antimicrobial resistance is an emerging problem with Pseudomonas aeruginosa. This
      study determined risk factors for the recovery of piperacillin-tazobactam
      resistant P. aeruginosa from clinical cultures from hospitalized patients. A case
      control study design was used to compare two groups of case patients with control
      patients. The first group of case patients was defined by nosocomial isolation of
      piperacillin-tazobactam-resistant P. aeruginosa, and the second group of cases
      yielded piperacillin-tazobactam-susceptible P. aeruginosa. Controls were selected
      in a 6:1 ratio from the same medical or surgical services among which
      piperacillin-tazobactam-resistant P. aeruginosa arose in patients. Risk factors
      analyzed included antimicrobial drug exposure, comorbid conditions, and
      demographics. Bivariate and multivariable analyses were performed. Piperacillin
      tazobactam-resistant P. aeruginosa was isolated from 179 patients, and
      piperacillin-tazobactam-susceptible P. aeruginosa was isolated from 624 patients
      over a 2.5-year period. Piperacillin-tazobactam (odds ratio [OR] = 6.82; 95%
      confidence interval [CI], 4.56 to 10.21), imipenem (OR = 2.42; 95% CI, 1.19 to
      4.94), aminoglycosides (OR = 2.18; 95% CI, 1.44 to 3.28), vancomycin (OR = 1.87;
      95% CI, 1.21 to 2.89), and broad-spectrum cephalosporins (OR = 2.38; 95% CI, 1.45
      to 3.88) were the antibiotics associated with the isolation of piperacillin
      tazobactam-resistant P. aeruginosa. Exposure to vancomycin (OR = 1.53; 95% CI,
      1.13 to 2.06) or ampicillin-sulbactam (OR = 2.28; 95% CI, 1.62 to 3.21) was
      associated with recovery of piperacillin-tazobactam-susceptible P. aeruginosa. In
      this study, antibiotics associated with piperacillin-tazobactam-susceptible P.
      aeruginosa were different from antibiotics associated with piperacillin
      tazobactam-resistant P. aeruginosa. Piperacillin-tazobactam was a strong risk
      factor for piperacillin-tazobactam-resistant P. aeruginosa. Our results suggest
      that the nosocomial isolation of piperacillin-tazobactam-resistant P. aeruginosa
      may be affected by multiple antibiotics.

PMID- 11850271
TI  - Quantitative PCR assay to evaluate ampicillin, ofloxacin, and doxycycline for
      treatment of experimental leptospirosis.
AB  - The susceptibility of Leptospira interrogans serovar icterohaemorrhagiae strain
      Verdun to selected antibiotics used in medical practice (ampicillin, doxycycline,
      and ofloxacin) was evaluated in a Syrian hamster model, to determine the efficacy
      of these antibiotics during the course of the disease. A quantitative PCR assay
      was used to monitor the density of leptospires in blood and in target organs
      (liver, kidney, lung, heart, and spleen). Our results demonstrated the ability of
      ampicillin at a high dose (100 mg/kg of body weight) to clear leptospires from
      the host, except from kidneys and heart, where 10(2) leptospires/g remained at
      day 6. Ofloxacin (30 mg/kg) was unable to clear bacteria from blood or kidneys.
      With doxycycline (10 mg/kg), the clearance of leptospires occurred in 2 days in
      all the target organs studied, with the exception of liver, which required 3
      days. Our data demonstrate the value of monitoring the kinetics of experimental
      leptospiral infection in order to accurately evaluate the efficacy of
      antibiotics. We have demonstrated the potential value of doxycycline for the
      treatment of leptospirosis cases, except in circumstances where it is
      contraindicated. This experimental model could be used to define better
      therapeutic strategies for human leptospirosis, by testing associations or new
      formulations of antibiotics.

PMID- 11850273
TI  - Optimal dose of amoxicillin in treatment of otitis media caused by a penicillin
      resistant pneumococcus strain in the gerbil model.
AB  - Amoxicillin at doses of 0.2 to 5 mg/kg of body weight was administered for the
      treatment of pneumococcal otitis media in a gerbil model. Doses greater than or
      equal to 2.5 mg/kg, which resulted in concentrations in middle ear fluid of > or
      = 1.4 microg/ml and concentrations in serum higher than the MIC (1 microg/ml) for
      > or = 14% of the dosing interval, were both clinically and bacteriologically
      effective.

PMID- 11850274
TI  - Mutator bacteria as a risk factor in treatment of infectious diseases.
AB  - We show in a gnotobiotic mouse model that, in addition to direct selection of
      antibiotic-resistant bacteria, some antibiotic treatments also select for mutator
      alleles. Because of these mutator alleles' high mutation rates, the initial
      treatment failure increases the probability of failures in subsequent treatments
      with other drugs.

PMID- 11850276
TI  - In vitro activities of BAL9141, a novel broad-spectrum pyrrolidinone
      cephalosporin, against gram-negative nonfermenters.
AB  - The activities of BAL9141 (formerly Ro 63-9141), a novel pyrrolidinone-3
      ylidenemethyl cephalosporin, against 244 strains of gram-negative nonfermenters
      were evaluated. The overall MIC at which 50% of isolates are inhibited (MIC50)
      and the overall MIC90 were 2 and 64 microg/ml, respectively, which are similar to
      those of imipenem, lower than those of the other cephalosporins tested,
      amoxicillin, and the ticarcillin-clavulanic acid combination, and much higher
      than those of ciprofloxacin. BAL9141 shows species-dependent activity in vitro
      against a variety of gram-negative nonfermentative pathogens.

PMID- 11850275
TI  - In vitro activities of the des-fluoro(6) Quinolone BMS-284756 against aerobic and
      anaerobic pathogens isolated from skin and soft tissue animal and human bite
      wound infections.
AB  - BMS-284756, a new des-fluoro(6) quinolone, was very active against 240 aerobic
      and 180 anaerobic isolates from bite victims. It inhibited 403 of 420 (96%)
      isolates, including those of Moraxella spp., CDC group EF-4, and Eikenella
      corrodens at < or = 2 microg/ml and those of all Pasteurella spp. and Bergeyella
      zoohelcum at < or = 0.015 microg/ml. Fusobacterium russii and 6 of 11
      Fusobacterium nucleatum isolates of animal bite origin were resistant, but
      isolates of human bite origin were susceptible, which suggests that they were of
      a different subspecies.

PMID- 11850278
TI  - High prevalence of oxacillin-resistant Staphylococcus aureus isolates from
      hospitalized patients in Asia-Pacific and South Africa: results from SENTRY
      antimicrobial surveillance program, 1998-1999.
AB  - As part of the SENTRY antimicrobial surveillance program, we examined the
      prevalence rates, types, and antibiograms of oxacillin-resistant Staphylococcus
      aureus from hospitalized patients from 17 institutions in eight countries in Asia
      Pacific and South Africa (APAC). From April 1998 to December 1999, a total of
      1,711 isolates of S. aureus (814 from blood, 392 from the respiratory tract, 467
      from skin and skin structures, and 38 from urine) were collected from
      hospitalized patients within the APAC region. Multidrug-resistant oxacillin
      resistant S. aureus (MORSA) isolates, defined as strains with three or more
      resistances to drug classes other than beta-lactams, were the most common type of
      oxacillin-resistant S. aureus (ORSA). They were the most frequently identified
      pathogen in wound infections and were common in bloodstream and lower respiratory
      tract infections. In all contributing institutions combined, more than 45%
      (range, 4 to 74%) of S. aureus isolates were oxacillin resistant, and in six
      institutions, this rate exceeded 60%. MORSA accounted for 91.2% of all oxacillin
      resistant isolates. Distinct resistance patterns predominated at various sites
      within the APAC region, suggesting the local evolution of resistant clones. Non
      multidrug-resistant strains were frequent in one part of Australia. No vancomycin
      intermediate strains were detected, and no strains were resistant to linezolid or
      quinupristin-dalfopristin. MORSA strains are a very common cause of infection in
      hospitalized patients in the APAC region.

PMID- 11850277
TI  - Activities of polymyxin B and cecropin A-,melittin peptide CA(1-8)M(1-18) against
      a multiresistant strain of Acinetobacter baumannii.
AB  - Polymyxin B (PXB) and the cecropin A-melittin hybrid CA(1-8)M(1-18)
      (KWKLFKKIGIGAVLKVLTTGLPALIS-NH2) were compared for antibiotic activity on
      reference and multiresistant Acinetobacter baumannii strains. Significant
      differences for both peptides were observed on their inner membrane interaction
      and inhibition by environmental factors, supporting the use of CA(1-8)M(1-18) as
      a potential alternative to PXB against ACINETOBACTER:

PMID- 11850279
TI  - Antitrypanosomal activities of tryptanthrins.
AB  - New drugs and molecular targets are needed against Trypanosoma brucei, the
      protozoan that causes African sleeping sickness. Tryptanthrin (indolo[2,1
      b]quinazoline-6,12-dione), a traditional antifungal agent, and 11 analogs were
      tested against T. brucei in vitro. The greatest activity was conferred by
      electron-withdrawing groups in the 8 position of the tryptanthrin ring system;
      the most potent compound had a 50% effective concentration of 0.40 microM.

PMID- 11850280
TI  - International interlaboratory quality control program for measurement of
      antiretroviral drugs in plasma.
AB  - An international interlaboratory quality control program for measurement of
      antiretroviral drugs was initiated. The first round was confined to protease
      inhibitors and showed large variability in the performance of participating
      laboratories. The results demonstrate the need for and utility of an ongoing
      quality control program in this area of bioanalysis.

PMID- 11850282
TI  - In vitro activities of tigecycline (GAR-936) against recently isolated clinical
      bacteria in Spain.
AB  - The antimicrobial activities of tigecycline (GAR-936) were compared with those of
      other agents against 1,087 strains recently isolated in 12 Spanish medical
      centers. Tigecycline showed activity against a wide spectrum of aerobic and
      anaerobic bacteria, including strains such as methicillin-resistant
      Staphylococcus aureus, coagulase-negative staphylococci, penicillin-resistant
      Streptococcus pneumoniae, Enterococcus faecium, Acinetobacter baumannii, and
      Stenotrophomonas maltophilia.

PMID- 11850281
TI  - Novel use of a guanosine prodrug approach to convert 2',3'-didehydro-2',3'
      dideoxyguanosine into a viable antiviral agent.
AB  - Transient kinetic studies with human immunodeficiency virus (HIV) type 1 reverse
      transcriptase suggest that nucleotide analogs containing the 2',3'-didehydro
      2',3'-dideoxy ribose ring structure present in D4T (stavudine) triphosphate are
      among the most effective alternative substrates. For unclear reasons, however,
      the corresponding purine nucleoside, 2',3'-didehydro-2',3'-dideoxyguanosine
      (D4G), was found to be inactive in cell culture. We have found that the
      previously reported lack of activity of D4G is primarily due to solution
      instability, and in this report we describe a novel use of a guanosine prodrug
      approach to stabilize the nucleoside. D4G was modified at the 6 position of the
      purine ring to contain a cyclopropylamino group yielding the prodrug, cyclo-D4G.
      An evaluation of cyclo-D4G revealed that the prodrug possessed anti-HIV activity.
      In addition, cyclo-D4G had increased stability, lipophilicity, and solubility, as
      well as decreased toxicity relative to D4G, suggesting that further study is
      warranted.

PMID- 11850283
TI  - Stable concentrations of zidovudine, stavudine, lamivudine, abacavir, and
      nevirapine in serum and cerebrospinal fluid during 2 years of therapy.
AB  - For a number of antiretroviral drugs, prolonged suppression of viral replication
      is related to drug exposure. Therefore, it is important to maintain stable
      concentrations during prolonged therapy. While studies suggest that saquinavir
      concentrations decrease over time, we show that concentrations of zidovudine,
      stavudine, lamivudine, abacavir, and nevirapine in serum and cerebrospinal fluid
      are stable during 2 years of therapy.

PMID- 11850285
TI  - In vitro antibacterial activities of DQ-113, a potent quinolone, against clinical
      isolates.
AB  - The antibacterial activity of DQ-113, formerly D61-1113, was compared with those
      of antibacterial agents currently available. MICs at which 90% of the isolates
      tested are inhibited (MIC90s) of DQ-113 against clinical isolates of methicillin
      susceptible and -resistant Staphylococcus aureus and methicillin-susceptible and 
      resistant coagulase-negative staphylococci were 0.03, 0.008, 0.03, and 0.06
      microg/ml, respectively. Moreover, DQ-113 showed the most potent activity against
      ofloxacin-resistant and methicillin-resistant S. aureus, with a MIC90 of
      0.25microg/ml. DQ-113 inhibited the growth of all strains of Streptococcus
      pneumoniae, including penicillin-resistant strains, and Streptococcus pyogenes at
      0.06 microg/ml, and DQ-113 was more active than the other quinolones tested
      against Enterococcus faecalis and Enterococcus faecium with MIC90s of 0.25 and 2
      microg/ml, respectively. Against vancomycin-resistant enterococci, DQ-113 showed
      the highest activity among the reference compounds, with a MIC range from 0.25 to
      2 microg/ml. DQ-113 also showed a potent activity against Haemophilus influenzae,
      including ampicillin-resistant strains (MIC90, 0.015 microg/ml), and Moraxella
      catarrhalis (MIC90, 0.03 microg/ml). The activity of DQ-113 was roughly
      comparable to that of levofloxacin against all species of ENTEROBACTERIACEAE: The
      MICs of DQ-113 against ofloxacin-susceptible Pseudomonas aeruginosa ranged from
      0.25 to 2 microg/ml, which were four times higher than those of ciprofloxacin.
      From these results, DQ-113 showed the most potent activity against gram-positive
      pathogens among antibacterial agents tested.

PMID- 11850284
TI  - Penetration of rifampin through Staphylococcus epidermidis biofilms.
AB  - Rifampin penetrated biofilms formed by Staphylococcus epidermidis but failed to
      effectively kill the bacteria. Penetration was demonstrated by a simple diffusion
      cell bioassay and by transmission electron microscopic observation of antibiotic
      affected cells at the distal edge of the biofilm.

PMID- 11850286
TI  - Extent of cross-resistance between agents used to treat human immunodeficiency
      virus type 1 infection in clinically derived isolates.
AB  - The phenomenon of cross-resistance to antiretroviral agents used to treat human
      immunodeficiency virus type 1 infection is well known but so far has been only
      qualitatively described. Here, we quantitate the degree of cross-resistance among
      all commonly prescribed antiretroviral agents in almost 5,000 clinically derived
      recombinant isolates collected in the United States since January 2000.

PMID- 11850287
TI  - Rational dose selection for a nonnucleoside reverse transcriptase inhibitor
      through use of population pharmacokinetic modeling and Monte Carlo simulation.
AB  - In order to choose a rational dose for GW 420867X, we first set a goal of
      therapy. We hypothesized that, for optimal antiretroviral activity, the trough
      free drug concentration should remain above the 90% effective concentration
      (EC90) of human immunodeficiency virus type 1. We performed population
      pharmacokinetic analysis on three different doses of GW 420867X (50, 100, and 200
      mg). Monte Carlo simulation was performed, assuming a log-normal distribution for
      1,000 simulated subjects for each dose, and was repeated three times. The trough
      concentrations were divided by 76 to account for protein binding and for the
      difference between EC50 and EC90. We then determined the fraction of the
      simulated population whose free drug trough concentrations would exceed an EC90
      over a broad range of values. The target attainment for all three doses exceeded
      95% out to a starting EC50 of 10 nM. For 16 viral isolates, the EC50 range
      encountered for GW 420867X did not exceed 8 nM, implying that the three doses
      could not be differentiated by effect in a clinical trial in naive patients. This
      prediction was shown to be correct in a randomized, double-blind trial with 1
      week of monotherapy with GW 420867X.

PMID- 11850288
TI  - Intrapulmonary pharmacokinetics of telithromycin, a new ketolide, in healthy
      Japanese volunteers.
AB  - The concentrations of telithromycin, a new ketolide antimicrobial agent, in
      alveolar macrophages (AMs) and bronchoalveolar epithelial lining fluid (ELF) were
      determined in order to investigate the transfer of the drug into target tissue,
      relative to plasma, following multiple oral doses of telithromycin. Twenty-four
      healthy male Japanese volunteers were randomly allocated to four groups. Each
      subject was given 600 or 800 mg of telithromycin once daily for 5 days, followed
      by bronchoalveolar lavage (BAL) 2 or 8 h after the last dose (group A and B: 600
      mg, 2 and 8 h BAL time point; group C and D: 800 mg, 2 and 8 h BAL time point).
      The mean concentrations of the drug in AMs and ELF were 34.54 and 4.92 mg/liter
      in group A, 50.97 and 2.26 mg/liter in group B, 25.47 and 4.24 mg/liter in group
      C, and 108.22 and 4.31 mg/liter in group D, respectively, which markedly exceeded
      concentrations in plasma. These results demonstrated good transfer of
      telithromycin into AMs and ELF, suggesting good efficacy against common
      respiratory pathogens, including intracellular pathogens and atypical
      microorganisms.

PMID- 11850289
TI  - Efficacy of ravuconazole in treatment of systemic murine histoplasmosis.
AB  - Ravuconazole (RCZ) was evaluated for efficacy in comparison to fluconazole (FCZ)
      and itraconazole (ITZ) in murine models of disseminated histoplasmosis. All
      regimens tested prolonged survival (P < 0.05 to 0.0001). At equivalent doses of
      50 mg/kg of body weight, RCZ and ITZ were equally effective and RCZ was more
      effective than FCZ (P = 0.02). Clearance of fungal burden from the livers and
      spleens of mice showed RCZ and ITZ at doses of 50 mg/kg to be efficacious but not
      curative. These data indicate that RCZ should be studied further.

PMID- 11850290
TI  - Characterization of a new extended-spectrum beta-lactamase (TEM-87) isolated in
      Proteus mirabilis during an Italian survey.
AB  - A new natural TEM derivative, named TEM-87, was identified in a Proteus mirabilis
      isolate from an Italian hospital. Compared to TEM-1, TEM-87 contains the
      following mutations: E104K, R164C, and M182T. Kinetic analysis of TEM-87 revealed
      extended-spectrum activity against oxyimino cephalosporins (preferentially
      ceftazidime) and aztreonam. Expression of blaTEM-87 in Escherichia coli decreased
      the host susceptibility to these drugs.

PMID- 11850291
TI  - In vivo activities of farnesyl pyrophosphate synthase inhibitors against
      Leishmania donovani and Toxoplasma gondii.
AB  - The in vivo activities of three bisphosphonates were determined against
      Leishmania donovani and Toxoplasma gondii. Alendronate was essentially inactive
      against both parasites. Pamidronate was active against L. donovani by intravenous
      administration. Risedronate had a 50% effective dosage of five 2.6-mg/kg of body
      weight intraperitoneal doses against L. donovani-infected mice but was less
      effective against T. gondii-infected mice.

PMID- 11850292
TI  - First isolation of a carbapenem-hydrolyzing beta-lactamase in Pseudomonas
      aeruginosa in Spain.

PMID- 11850293
TI  - In vitro activities of novel des-fluoro(6) quinolone BMS-284756 against mutants
      of Streptococcus pneumoniae, Streptococcus pyogenes, and Staphylococcus aureus
      selected with different quinolones.

PMID- 11850294
TI  - Cerebrospinal fluid linezolid concentrations in postneurosurgical central nervous
      system infections.

PMID- 11850297
TI  - The future of Age and Ageing.

PMID- 11850295
TI  - Importance of species selection in arrythmogenic models of Q-T interval
      prolongation.

PMID- 11850298
TI  - Treatment bias and clinical judgement.

PMID- 11850299
TI  - Photodynamic therapy for age-related macular degeneration.

PMID- 11850300
TI  - Creutzfeldt-Jakob disease in elderly people.

PMID- 11850301
TI  - The end of age: but not for the worse off.

PMID- 11850302
TI  - 'Guideline for the prevention of falls in older persons': essential reading.

PMID- 11850303
TI  - Air travel in older people.
AB  - Commercial air travel is one of the safest means of transport. However, the
      environment within the aircraft cabin may have deleterious physiological effects
      on passengers, especially those with underlying medical problems and those who
      are old. With growing affluence, cheaper airfares and an ageing population, there
      will be more older people travelling by air over extended periods and longer
      distances, with a concomitant rise in the number of medical illnesses in the air.
      Older people may encounter various problems during a long journey. Certain
      actions may help to minimize these problems.

PMID- 11850304
TI  - Beta-blockers in left ventricular systolic dysfunction--from evidence to
      practice.
AB  - Five percent of all hospital medical admissions are patients with heart failure.
      The incidence is about one new case per 1000 of the general population per year,
      increasing to >10 per 1000 in those aged >or=85 years. Although the evidence that
      beta-blockers reduce mortality by about 36% when added to angiotensin-converting
      enzyme inhibitors is overwhelming, clinicians are still reluctant to use beta
      blockers in heart failure, especially in older patients. Here, we examine the
      evidence for the use of beta-blockers in heart failure in older people and
      explore the practicalities of their use.

PMID- 11850305
TI  - Heart failure in older people: causes, diagnosis and treatment.
AB  - Congestive heart failure affects >5% of those aged 65-75 and 10-20% of those aged
      >80 in the UK, and levels are likely to rise in the wake of improved therapies
      for hypertension and myocardial infarction. It is often multifactorial in this
      group. The most common causes are hypertension and coronary heart disease, with
      valvular heart disease playing an increasing role. The most common precipitant of
      pre-existing heart failure is non-compliance with medication or diet; non
      steroidal anti-inflammatory drugs are particularly likely to exacerbate the
      condition. Diagnosis may be difficult since typical signs are often absent or
      masked in older people, but plasma levels of brain natriuretic peptide appear to
      be a reliable indicator and may provide diagnostic test in the future. Systolic
      heart failure is managed by conventional therapy (diuretics, angiotensin
      converting enzyme inhibitors and beta-blockers). The management of diastolic
      heart failure is less well defined, but symptoms should be managed, ischaemia
      prevented and the underlying causes identified and treated. Nurse-directed,
      multidisciplinary intervention (including education of patient and family, social
      support, review of medication, dietary modification and weight monitoring) have
      resulted in improvements in event-free survival and quality of life.

PMID- 11850306
TI  - Age- and sex-related bias in the management of heart disease in a district
      general hospital.
AB  - OBJECTIVE: To investigate the clinical management of heart disease and determine
      whether there was age- and sex-related bias in the use of investigations and
      interventions. DESIGN: Retrospective analysis of individual patient records
      against criteria of appropriateness based on published guidelines, clinical
      practice and literature relevant to the 1996-7 study period. SETTING: A single,
      district general hospital in London, serving a population of 185,000 people.
      SUBJECTS: General medical, elderly medical, and cardiology inpatients and
      patients attending elderly medical and cardiology outpatient clinics as new
      referrals between 1 April 1996 and 31 March 1997. RESULTS: We located case notes
      of 1790 of the 1975 subjects eligible for the study: 911 (51%) were outpatients
      and 51% were men. Patients aged <75 were significantly more likely than patients
      aged >or=75 years to be given thrombolysis after an acute myocardial infarction,
      to be given secondary prevention with aspirin and beta-blockers, to undergo
      exercise testing and coronary angiography, and to receive an echocardiogram. Men
      were also significantly more likely than women to have these investigations and
      interventions as well as to receive an angiotensin-converting enzyme inhibitor
      when left ventricular dysfunction was identified. Investigations and
      interventions were underused at all ages. CONCLUSION: As well as identifying age
      and sex bias, we found the underuse of investigations and interventions in all
      age groups in this district general hospital. Should similar patterns of care be
      found elsewhere, the delivery of high-quality care in an equitable manner (as
      identified by the National Service Framework for coronary heart disease) may
      require considerably more resources than have been allocated.

PMID- 11850307
TI  - Vascular disease and cognitive function in older men in the Caerphilly cohort.
AB  - OBJECTIVES: Stroke can impair cognitive function, but the associations between
      other manifestations of vascular disease and cognitive function have not been
      adequately studied in representative population samples of subjects. We report
      the associations between cardiac and peripheral vascular disease and cognitive
      function for a large representative sample of men in Caerphilly, South Wales, UK.
      DESIGN: The Caerphilly cohort is the basis of on-going studies of vascular
      disease, of cognitive function and of predictors of these. We have made intensive
      attempts to identify all cases of vascular disease: myocardial infarction,
      angina, ECG ischaemia, peripheral vascular disease (intermittent claudication)
      and stroke. Here we present data on associations between vascular disease and
      cognitive function. SETTING: The study is based upon a representative population
      sample of over 1,500 men in South Wales, aged 55-69 years when cognitive function
      was measured. The men, and hospital and GP notes relating to them, had been
      repeatedly examined for evidence of vascular disease during the previous ten
      years. MAIN OUTCOME MEASURES: Standard tests of cognitive function: the AH4,
      CAMCOG, MMSE and choice reaction time. RESULTS: After the omission of men who had
      had a stroke, we detected significant associations between cognitive function and
      the presence of angina, ECG ischaemia, past myocardial infarction and
      intermittent claudication. The strength of the associations between cognitive
      function and the various manifestations of vascular disease were similar, and the
      various cognitive function tests showed effects of similar size. Overall, cardiac
      and peripheral vascular disease is associated with a significant reduction in
      cognitive function equivalent to about one sixth of the standard deviation of a
      number of tests of cognitive function. The size of this effect is roughly
      equivalent to the decline in cognitive performance over five years of ageing.
      CONCLUSIONS: Subjects with evidence of cardiac or peripheral vascular disease
      have on average a significant reduction in cognitive function equivalent to about
      four or five years of additional age. The effect of long-term, low-dose aspirin
      on cognitive decline should now be tested.

PMID- 11850308
TI  - Intensive physical training in geriatric patients after severe falls and hip
      surgery.
AB  - BACKGROUND: Intensive exercise training can lead to improvement in strength and
      functional performance in older people living at home and nursing home residents.
      There is little information whether intensive physical exercise may be applicable
      and effective in elderly patients suffering from the acute sequelae of injurious
      falls or hip surgery. OBJECTIVE: To assess the feasibility, safety and efficacy
      of intensive, progressive physical training in rehabilitation after hip surgery.
      DESIGN: Prospective, randomised, placebo-controlled intervention study of a 3
      months training intervention and a 3-months' follow-up. SETTING: Physical
      training 6-8 weeks after hip surgery. SUBJECTS: Twenty-eight (15 intervention, 13
      control) elderly patients with a history of injurious falls admitted to acute
      care or inpatient rehabilitation because of acute fall-related hip fracture or
      elective hip replacement. METHODS: Progressive resistance and functional training
      to improve strength and functional performance. RESULTS: No training-related
      medical problems occurred in the study group. Twenty-four patients (86%)
      completed all assessments during the intervention and follow-up period. Adherence
      was excellent in both groups (intervention: 93, 0+/-13, 5% versus control: 96,
      7+/-6, 2%). Training significantly increased strength, functional motor
      performance and balance and reduced fall-related behavioural and emotional
      problems. Some improvements in strength persisted during 3-months follow-up while
      other strength variables and functional performances were lost after cessation of
      training. Patients in the control group showed no change in strength, functional
      performance and emotional state during intervention and follow-up. CONCLUSIONS:
      Progressive resistance training and progressive functional training are safe and
      effective methods to increase strength and functional performance during
      rehabilitation in patients after hip surgery and a history of injurious falls.
      Because part of the training improvements were lost after stopping the training,
      a continuing training regime should be established.

PMID- 11850309
TI  - Dementia and use of psychotropic medication in non-'Elderly Mentally Infirm'
      nursing homes in South East England.
AB  - BACKGROUND: There is concern about inappropriate use of psychotropic medication
      in nursing homes in the UK. Older people with advanced dementia, who might need
      such medication, are supposed to be admitted to specialist 'Elderly Mentally
      Infirm' homes. OBJECTIVES: To estimate the prevalence of dementia and
      psychotropic medication use in UK non-Elderly Mentally Infirm homes. DESIGN: a)
      Probability sample of non-elderly mentally infirm places in nursing-homes in
      South-East England then b) two-stage survey of a probability sample of residents
      in these places SETTING: Non-Elderly Mentally Infirm nursing homes for older
      people in SE England. SUBJECTS: Residents registered non-Elderly Mentally Infirm
      homes. METHODS: Assessment using mini mental state examination for cognitive
      impairment, the Behave-AD for behavioural problems and the Cornell Scale for
      depression. Mini mental state examination scores were validated against
      independent psychiatric assessment in a sub-sample of residents. We gathered
      medication data from prescription sheets. RESULTS: Of the 445 residents 74%
      assessed had probable clinical dementia. Of all the residents 38% had severe
      cognitive impairment, with a three-fold higher rate of behavioural disturbance
      than others. Psychotropic medication was strongly associated with cognitive
      impairment. Antipsychotic drugs were prescribed for only 15% of all residents.
      CONCLUSIONS: If nearly three-quarters of non-Elderly Mentally Infirm nursing home
      residents have dementia, many with behavioural disturbance, then dementia care is
      not a 'specialist' area of nursing home care. This study offers no support for
      the hypothesis that use of antipsychotic drugs in nursing homes is excessive.
      Questions are raised about policy, staffing and training in nursing homes.

PMID- 11850311
TI  - Hip pathology can masquerade as knee pain in adults.

PMID- 11850310
TI  - Refeeding syndrome.
AB  - CASE REPORT: An elderly woman with poor nutritional intake developed profound
      hypophosphataemia and hypokalaemia following the institution of nasogastric
      feeding. DISCUSSION: Refeeding syndrome is well recognized in certain
      undernourished groups of patients, but may not be so well known to physicians
      looking after elderly patients, whose nutritional status may be more deficient
      than is originally apparent.

PMID- 11850312
TI  - Dedicated to elderly care: geriatric medicine on the internet.
AB  - The internet and world wide web make it easier for professionals, patients and
      carers to access medical expertise and technology. Websites providing information
      about geriatric medicine and gerontology include those of general and specialized
      journals and textbooks--including publications on geriatric psychiatry, geriatric
      emergency medicine, nutrition, ethics and law and geriatric nursing--and those of
      professional and research organisations. Also of use are sites related to allied
      branches of medicine--particularly dementia, stroke, Parkinson's disease, pain
      and geriatric rehabilitation. Topic-based mailing lists facilitate discussion; in
      addition, some websites include discussions areas. Information specifically
      targeted at patients and carers is available at sites created by research
      charities and patient information and support groups.

PMID- 11850313
TI  - Preventing patient falls.

PMID- 11850314
TI  - Amnesia treated successfully.

PMID- 11850315
TI  - Ulcerative cuteanous sarcoidosis masquerading as metastatic carcinoma of the
      breast.

PMID- 11850316
TI  - Headache and Alzheimer's disease.

PMID- 11850317
TI  - Colonoscopy in older patients: a safe and sound practice.

PMID- 11850318
TI  - Publications by registrars completing higher specialist training in geriatric
      medicine in the United Kingdom in 1999/2000.

PMID- 11850321
TI  - Misconceptions--what students think they know.

PMID- 11850323
TI  - Aldosterone.
AB  - Aldosterone plays a pivotal role in electrolyte and fluid homeostasis and thus
      control of blood pressure. The "classical" view of aldosterone action is that it
      targets epithelia of the distal colon and renal nephron to stimulate Na(+)
      (re)absorption and K(+) secretion. In these cells, aldosterone binds steroid
      receptors, promoting translocation to the nucleus, where they modulate gene
      expression with the induced proteins stimulating transport. This "genomic" action
      is dependent on transcription and translation and has a latency of 0.5-1.0 h.
      Recently, more rapid actions of aldosterone that are independent of transcription
      and translation have been described. These "nongenomic" actions are mediated by a
      distinct receptor that is insensitive to inhibitors of the classical
      mineralocorticoid receptor, such as spironolactone. The present review describes
      advances in our understanding of the classical model of aldosterone action as
      well as those that broaden this model to encompass nongenomic actions,
      nonepithelial targets, production of aldosterone outside of the adrenal gland,
      novel mechanisms of specificity, and novel mechanisms for mediating genomic
      actions.

PMID- 11850324
TI  - The effectiveness of web-based, multimedia tutorials for teaching methods of
      human body composition analysis.
AB  - This study examined the effectiveness of a series of Web-based, multimedia
      tutorials on methods of human body composition analysis. Tutorials were developed
      around four body composition topics: hydrodensitometry (underwater weighing),
      dual-energy X-ray absorptiometry, bioelectrical impedance analysis, and total
      body electrical conductivity. Thirty-two students enrolled in the course were
      randomly assigned to learn the material through either the Web-based tutorials
      only ("Computer"), a traditional lecture format ("Lecture"), or lectures
      supplemented with Web-based tutorials ("Both"). All students were administered a
      validated pretest before randomization and an identical posttest at the
      completion of the course. The reliability of the test was 0.84. The mean score
      changes from pretest to posttest were not significantly different among the
      groups (65.4 plus minus 17.31, 78.82 plus minus 21.50, and 76 plus minus 21.22
      for the Computer, Both, and Lecture groups, respectively). Additionally, a Likert
      type assessment found equally positive attitudes toward all three formats. The
      results indicate that Web-based tutorials are as effective as the traditional
      lecture format for teaching these topics.

PMID- 11850325
TI  - "Survivor" torches "Who Wants to Be a Physician?" in the educational games
      ratings war.
AB  - We recently developed an educational game for reviewing respiratory physiology in
      a large classroom. The "Who Wants to be a Physician?" game encouraged medical
      students to be active participants in the learning process. An evaluation of the
      game documented that students enjoyed the active format, and the students
      reported that the game enhanced their ability to understand and retain
      information. However, the evaluation also revealed that the game had limitations.
      Specifically, the students recommended the use of multiple-choice questions to
      match the Medical Board Examination format and to speed up the game (i.e., cover
      more topics). The students also wanted to increase their level of participation
      and interaction. Finally, we wanted to emphasize the benefits of peer instruction
      as a collaborative learning tool. To address these limitations, we designed a new
      game, "Survivor." Survivor incorporated multiple-choice questions and emphasized
      peer instruction and a capacity to gather information and solve novel problems.
      In addition, participation was increased by including the student audience in the
      game. Finally, an evaluation instrument was utilized to assess the effectiveness
      of this instructional tool in an academic setting. As a result of these
      improvements, the evaluation documents that the newly developed tool is a more
      effective educational game that couples fun and creative excitement with proven
      and effective educational concepts.

PMID- 11850326
TI  - Collaborative testing enhances student learning.
AB  - Examinations and quizzes should be used as learning as well as assessment tools.
      To achieve this goal, an assessment procedure was developed to enhance as well as
      assess student learning. Students were tested on four different topics of
      cardiovascular physiology. Each topic was tested by a different type of quiz
      (fill in the blanks, single best response multiple choice, short essay, or
      true/false). The students first completed a quiz individually. Once the quiz was
      completed individually, the students completed the same quiz in groups. Eighty
      percent of the score on the quiz was based on the individual results, and 20% of
      the score on the quiz was based on the group results. The performance on the
      quizzes was significantly higher (P < 0.001) when students completed the quizzes
      in groups than when they completed the quizzes individually. Results document
      that completing the quizzes in groups enhances the understanding of the material.
      In addition, students rated this format superior to the traditional method.

PMID- 11850327
TI  - An intensive hands-on course designed to teach molecular biology techniques to
      physiology graduate students.
AB  - To address a growing need to make research trainees in physiology comfortable
      with the tools of molecular biology, we have developed a laboratory-intensive
      course designed for graduate students. This course is offered to a small group of
      students over a three-week period and is organized such that comprehensive
      background lectures are coupled with extensive hands-on experience. The course is
      divided into seven modules, each organized by a faculty member who has particular
      expertise in the area covered by that module. The modules focus on basic methods
      such as cDNA subcloning, sequencing, gene transfer, polymerase chain reaction,
      and protein and RNA expression analysis. Each module begins with a lecture that
      introduces the technique in detail by providing a historical perspective,
      describing both the uses and limitations of that technique, and comparing the
      method with others that yield similar information. Most of the lectures are
      followed by a laboratory session during which students follow protocols that were
      carefully designed to avoid pitfalls. Throughout these laboratory sessions,
      students are given an appreciation of the importance of proper technique and
      accuracy. Communication among the students, faculty, and the assistant
      coordinator is focused on when and why each procedure would be used, the
      importance of each step in the procedure, and approaches to troubleshooting. The
      course ends with an exam that is designed to test the students' general
      understanding of each module and their ability to apply the various techniques to
      physiological questions.

PMID- 11850328
TI  - Teaching human cardiovascular and respiratory physiology with the station method.
AB  - We have developed a station method to offer combined cardiovascular and
      respiratory physiology exercises all in one laboratory period during our medical
      physiology course. This laboratory was designed for first-year medical students
      in order to minimize equipment costs, maximize efficient use of both student and
      faculty time, and facilitate integration of basic cardiovascular concepts with
      those in respiratory physiology. We designed six stations for the students to
      evaluate: cardiovascular and respiratory responses to dynamic exercise, cold
      pressor reflex, postural influences and respiratory modulation of cardiovascular
      functions, forced expiratory maneuvers with inverted bell spirometers, forced
      expiratory maneuvers and maximal inspiratory maneuvers with electronic
      spirometers with and without obstruction, and respiratory muscle strength.
      Students worked in groups of two to four and were assessed by individual
      laboratory reports. Although we neglected to formally assess the impact on
      students of changes in laboratory design, students appeared to respond
      enthusiastically to the laboratory and prepared knowledgeable laboratory reports.

PMID- 11850329
TI  - International Union of Physiological Sciences teaching workshop, August 21-24,
      2001, Lincoln University, Lincoln, New Zealand.

PMID- 11850330
TI  - CT screening for lung cancer: is smaller better?

PMID- 11850331
TI  - Simple interventions--significant impact.

PMID- 11850332
TI  - "Routine" supportive care in the ICU: filtering out the bad news.

PMID- 11850333
TI  - Impact of a family information leaflet on effectiveness of information provided
      to family members of intensive care unit patients: a multicenter, prospective,
      randomized, controlled trial.
AB  - Comprehension and satisfaction are relevant criteria for evaluating the
      effectiveness of information provided to family members of intensive care unit
      (ICU) patients. We performed a prospective randomized trial in 34 French ICUs to
      compare comprehension of diagnosis, prognosis, treatment, and satisfaction with
      information provided by ICU caregivers, in ICU patient family representatives who
      did (n = 87) or did not (n = 88) receive a family information leaflet (FIL) in
      addition to standard information. An FIL designed specifically for this study was
      delivered at the first visit of the family representative: it provided general
      information on the ICU and hospital, the name of the ICU physician caring for the
      patient, a diagram of a typical ICU room with the names of all the devices, and a
      glossary of 12 terms commonly used in ICUs. Characteristics of the ICUs,
      patients, and family representatives were similar in the two groups. The FIL
      reduced the proportion of family members with poor comprehension from 40.9% to
      11.5% (p < 0.0001). In the representatives with good comprehension, the FIL was
      associated with significantly better satisfaction (21 [18 to 24, quartiles]
      versus 27 [24 to 29, quartiles], p = 0.01). These results indicate that ICU
      caregivers should consider using an FIL to improve the effectiveness of the
      information they impart to families.

PMID- 11850334
TI  - Incidence and mortality of acute lung injury and the acute respiratory distress
      syndrome in three Australian States.
AB  - To determine the incidence and 28-d mortality rate for acute lung injury (ALI)
      and acute respiratory distress syndrome (ARDS) using the 1994 American-European
      Consensus Conference definitions, we prospectively screened every admission to
      all 21 adult intensive care units in the States of South Australia, Western
      Australia, and Tasmania (total population older than 15 yr of age estimated as
      2,941,137), between October 1 and November 30, 1999. A total of 1,977 admissions
      were screened of which 168 developed ALI and 148 developed ARDS, which represents
      a first incidence of 34 and 28 cases per 100,000 per annum, respectively. The
      respective 28-d mortality rates were 32% and 34%. The most common predisposing
      factors for ALI were nonpulmonary sepsis (31%) and pneumonia (28%). Although the
      incidences of ALI and ARDS are higher and the mortality rates are lower than
      those reported from studies in other countries, multicenter international studies
      are required to exclude methodological differences as the cause for this finding.

PMID- 11850335
TI  - Protective effects of cyclosporin A from endotoxin-induced myocardial dysfunction
      and apoptosis in rats.
AB  - Myocardial depression can be demonstrated following administration of endotoxin.
      Proposed mechanisms of endotoxin-induced myocardial dysfunction include the
      release of proinflammatory mediators, focal myocardial ischemia, and the presence
      of activated leukocytes within the myocardium. Recently, myocardial caspase
      activation and mitochondria-related apoptotic events (i.e., release of cytochrome
      c) were demonstrated in the failing septic heart. Here, we tested the hypothesis
      that immunosuppressors, cyclosporin A and tacrolimus (FK 506), would improve
      inflammation, heart nuclear apoptosis, and myocardial dysfunction in endotoxin
      treated rats. Myocardial contractility was assessed using an isolated heart
      preparation. Heart leukocyte infiltration was assessed by measurement of heart
      myeloperoxidase activity. Leukocyte activation was studied using the intravital
      microscopy of the mesenteric venule. Apoptosis was detected as myocardial DNA
      fragmentation, downstream caspase activation, and mitochondrial cytochrome c
      release. Both cyclosporin A and FK 506 reduced heart leukocyte sequestration and
      venular adhesion in endotoxin-treated rats. Cyclosporin A, which blocks
      mitochondrial cytochrome c release, was able to reduce endotoxin-induced
      myocardial end-stage nuclear apoptosis and heart dysfunction, whereas tacrolimus
      had no such effects. These effects could be related to the unique properties of
      cyclosporin A to act on mitochondria.

PMID- 11850336
TI  - Improved arterial oxygenation with biologically variable or fractal ventilation
      using low tidal volumes in a porcine model of acute respiratory distress
      syndrome.
AB  - We compared biologically variable ventilation (V (bv); n = 9) with control mode
      ventilation (V (c); n = 8) at low tidal volume (VT)--initial 6 ml/kg--in a
      porcine model of acute respiratory distress syndrome (ARDS). Hemodynamics,
      respiratory gases, airway pressures, and VT data were measured. Static P-V curves
      were generated at 5 h. Interleukin (IL)-8 and IL-10 were measured in serum and
      tracheal aspirate. By 5 h, higher Pa(O(2)) (173 +/- 30 mm Hg versus 119 +/- 23 mm
      Hg; mean +/- SD; p < 0.0001 group x time interaction [G x T]), lower shunt
      fraction (6 +/- 1% versus 9 +/- 3%; p = 0.0026, G x T) at lower peak airway
      pressure (21 +/- 2 versus 24 +/- 1 cm H(2)O; p = 0.0342; G x T) occurred with V
      (bv). IL-8 concentrations in tracheal aspirate and wet:dry weight ratios were
      inversely related; p = 0.011. With V (c), IL-8 concentrations were 3.75-fold
      greater at wet:dry weight ratio of 10. IL-10 concentrations did not differ
      between groups. In both groups, ventilation was on the linear portion of the P-V
      curve. With V (bv), VT variability demonstrated an inverse power law indicating
      fractal behavior. In this model of ARDS, V (bv) improved Pa(O(2)) at lower peak
      airway pressure and IL-8 levels compared with V (c).

PMID- 11850337
TI  - Intratracheal endotoxin causes systemic inflammation in ventilated preterm lambs.
AB  - Intratracheal endotoxin causes acute inflammation in the adult lung, and
      injurious styles of mechanical ventilation can result in systemic inflammation
      derived from the lungs. We asked how ventilated premature and near-term lungs
      responded to intratracheal endotoxin and if systemic inflammation occurred. Lambs
      delivered at 130 d gestational age (GA) were treated with surfactant or
      surfactant plus endotoxin (0.1 mg/kg or 10 mg/kg) (Escherichia coli, serotype
      O55:B5) and were ventilated for 6 h. Both endotoxin doses resulted in impaired
      gas exchange and systemic inflammation in the preterm lambs. Lambs at 141 d GA
      (term 146 d) were given either 10 mg/kg intratracheal endotoxin, 10 mg/kg
      endotoxin plus high tidal volume ventilation for the first 30 min of life, or 5
      microg/kg endotoxin given intravenously. Endotoxin alone (10 mg/kg) caused lung
      inflammation but no systemic effects after 6 h of ventilation. Lambs given 10
      mg/kg endotoxin plus high tidal volume ventilation or 5 microg/kg endotoxin
      intravenously had decreased gas exchange and systemic inflammation. Endotoxin was
      detected in the plasma of lambs at 130 d GA but not at 141 d GA. Inflammation in
      the lungs was more severe in preterm animals. Mechanical ventilation of the
      endotoxin-exposed preterm lung resulted in systemic effects at a low endotoxin
      dose and without high tidal volume ventilation.

PMID- 11850338
TI  - An ELISA technique for quantification of surfactant apoprotein (SP)-C in
      bronchoalveolar lavage fluid.
AB  - Pulmonary surfactant apoprotein C (SP-C) is a small, unique peptide that
      contributes to the reduction of alveolar surface tension. Due to the extreme
      hydrophobic nature of this peptide it was hitherto not possible to quantify SP-C
      in biological samples by immunological techniques. Using a newly developed
      polyclonal antibody raised against recombinant human SP-C in rabbits, we now
      describe an enzyme-linked immunosorbent assay (ELISA) to quantitate SP-C in
      bronchoalveolar lavage fluid (BALF). Solid phase binding of the hydrophobic SP-C
      was achieved by transfer of the standard or BALF samples (diluted in 80%
      isopropanol, pH 3.5) to polystyrene microtiter plates. Sequential treatment with
      trifluoroethanol and methanol (2x) was employed to improve antigen presentation
      and to minimize the influence of phospholipids. With this assay, SP-C from human,
      rabbit, porcine, and bovine surfactant was detectable. No cross-reactivity of the
      antibody to human SP-A and monomeric and dimeric SP-B was encountered. Total
      serum proteins did not affect ELISA signals, as evident from spiking experiments.
      The detection limit of the ELISA ranged below 3 ng/ml, and intra- and interassay
      coefficients of variation were 3.5% (n = 16) and 5.3% (n = 6), respectively.
      Serial dilutions of BALF showed good linearity, and excellent recovery rates were
      obtained upon spiking of human BALF. A mean value of 579.5 +/- 45.9 ng/ml (mean
      +/- SEM) SP-C was found in BALF samples of human healthy volunteers (n = 22),
      corresponding to 26.61 +/- 1.91 microg SP-C/mg total phospholipids (PL). SP-C
      levels were significantly lower in BALF of patients with acute respiratory
      distress syndrome (ARDS) (286.9 +/- 19.8 ng/ml [p < 0.001]; 13.92 +/- 1.93 microg
      SP-C/mg PL [p < 0.001], n = 48). We conclude that SP-C may be quantified with
      high specificity, reproducibility, and sensitivity in bronchoalveolar lavage
      samples by the presently described ELISA technique and that SP-C levels are
      significantly decreased in ARDS.

PMID- 11850339
TI  - Polyethylene glycol (PEG) attenuates exogenous surfactant in lung-injured adult
      rabbits.
AB  - Exogenous surfactant administration in patients with the acute respiratory
      distress syndrome is currently being evaluated, although resource limitations and
      the potential expense are existing concerns. Previous in vitro and in vivo
      studies have shown that substances such as polyethylene glycol (PEG) added to
      exogenous surfactant improved the function of the surfactant. Based on these
      data, we hypothesized that PEG would augment surfactant function in an adult
      rabbit model of lung injury induced by lung lavage and mechanical ventilation,
      and that this would be accomplished by altering surfactant metabolism. Contrary
      to our hypothesis, however, mean Pa(O(2)), Pa(CO(2)), and peak inspiratory
      pressures values 3 h after treatment were significantly worse in the surfactant +
      PEG treatment groups compared with the surfactant alone groups. These effects
      were observed for two different doses of surfactant tested. Lavage analyses after
      sacrifice showed that animals given PEG with their surfactant had significantly
      lower total and large aggregate surfactant pool sizes compared with animals given
      surfactant alone. We conclude that in this lung injury model, PEG attenuated
      surfactant responses, suggesting that further preclinical studies are required
      before testing this approach in humans.

PMID- 11850340
TI  - Nitric oxide-dependent modulation of smooth-muscle tone by airway parasympathetic
      nerves.
AB  - We addressed the hypothesis that noncholinergic parasympathetic nerves modulate
      airway smooth-muscle (ASM) tone in guinea pigs. The NO synthase inhibitor L-N(G)
      nitro-arginine (L-NNA) and the guanylate cyclase inhibitor 1H
      [1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) potentiated cholinergic
      contractions and partly inhibited noncholinergic relaxations of the trachealis
      evoked by nerve stimulation in vitro or in situ. When delivered selectively to
      the trachea in situ, L-NNA and ODQ also increased baseline cholinergic tone of
      the trachealis, and L-NNA potentiated histamine-induced contractions of the
      trachealis in situ. L-Arginine prevented the effects of L-NNA. Vagotomy or
      selective nerve blockade with tetrodotoxin (TTX) mimicked the effects of L-NNA on
      histamine responses. The effects of TTX and L-NNA were not additive, however,
      suggesting that the two agents have common mechanisms of action, and indicating
      that other nonadrenergic, noncholinergic relaxant neurotransmitters lack
      influence under baseline conditions. When reflexly activated by bradykinin,
      noncholinergic parasympathetic nerves partly reversed histamine-induced
      contractions of the trachealis. L-NNA failed to inhibit this response, however,
      and did not potentiate the reflex tracheal cholinergic contractions produced by
      bradykinin. These results show that noncholinergic parasympathetic nerves
      modulate ASM tone. The NO-dependent component of this response is most effective
      at baseline levels of nerve activity.

PMID- 11850341
TI  - Effect of lung volume reduction surgery for severe emphysema on right ventricular
      function.
AB  - Lung volume reduction surgery (LVRS) can improve the functional capacity of
      selected patients with severe emphysema. Hypothesized physiologic effects of LVRS
      include an improvement in right ventricular function, although this has not been
      investigated in detail. To help clarify this issue, we used fast-thermistor
      thermodilution at rest and during submaximal upright exercise in 12 patients,
      before and 6 mo after bilateral LVRS. Preoperatively, all patients had severe
      airflow obstruction, with a mean FEV(1) of 0.69 L and an RV-to-TLC ratio of 0.67.
      Six months after LVRS, significant improvements occurred in respiratory function
      measures (+0.39 L in FEV(1), p < 0.002; and +/- 0.15 in RV/TLC ratio, p < 0.002)
      and in right ventricular function indexes measured at rest (+0.21 L in cardiac
      index [CI], p < 0.01; and +3.0 ml in stroke volume, p < 0.01) and during exercise
      (+0.9 L in CI, p < 0.002; +10.0 ml in stroke volume index, p < 0.002; and +20% in
      ejection fraction [EF], p < 0.002). A significant correlation was found between
      pre- to postoperative changes in the EF response to exercise and changes in the
      RV/TLC ratio (R = -0.68; p = 0.01). We conclude that a significant improvement in
      right ventricular performance, particularly during exercise, can occur 6 mo after
      bilateral LVRS.

PMID- 11850342
TI  - Pulmonary function, body composition, and protein catabolism in adults with
      cystic fibrosis.
AB  - Increased survival in cystic fibrosis (CF) is associated with bone thinning and
      fat-free mass (FFM) loss. We hypothesized that the severity of lung disease would
      be associated with increased protein catabolism and systemic inflammatory status
      in clinically stable patients. Forty adults with CF and 22 age-matched healthy
      subjects were studied. Body composition was determined by dual-energy X-ray
      absorptiometry. Urinary pseudouridine (PSU), a marker of protein breakdown, and
      cross-linked N-telopeptides of type I collagen (NTx), a marker of bone connective
      tissue breakdown, serum tumor necrosis factor (TNF)-alpha, interleukin (IL)-6,
      and their soluble receptors were measured. A 3-d food intake diary revealed 21
      patients had a low energy intake. Excretion of PSU (p = 0.019) and NTx (p < 0.01)
      was increased in patients and was inversely related to FEV(1); PSU (r = - 0.53, p
      = 0.001) and NTx (r = - 0.43, p < 0.01). Increased excretion of PSU and NTx (p <
      0.05 for both) was also related to a low FFM. All inflammatory mediators were
      greater in patients and were related to PSU and NTx. Clinically stable adults
      were catabolic with both cellular and connective tissue protein breakdown, which
      was related to lung disease severity, systemic inflammation, and body
      composition.

PMID- 11850343
TI  - Longitudinal profile of bronchoalveolar lavage cell characteristics in patients
      with a good outcome after lung transplantation.
AB  - Bronchoalveolar lavage fluid (BALF) analysis is used in patients after lung
      transplantation (LTX) to obtain more insight into pathological conditions such as
      acute and chronic allograft rejection. Information on the normal course of BALF
      cell characteristics in patients with "good outcome" after LTX is limited.
      Therefore we analyzed 169 BALF samples from 63 well-defined "good outcome"
      patients after LTX (no acute or chronic transplant dysfunction, bacterial,
      fungal, or viral infections at the time of BAL). Total cell count decreased from
      the first months: median (range) 234 x 10(3) (70-610) cells/ml to 103 x 10(3) (10
      840) cells/ml during the second year posttransplantation (p < 0.001). Cell
      differential counts did not change during the 2-yr study period. The CD4/CD8
      ratio increased significantly from 0.32 (0.11-0.46) just posttransplantation to
      0.62 (0.16-4.27) the second year after LTX. This increasing ratio was mainly due
      to a sharp decreasing CD8(+) cell count. Thus, characteristics of BAL cellular
      patterns in patients with good outcomes after LTX show important changes over
      time. We have defined control values for the BALF cellular profile in patients
      without pathological airway conditions after LTX. We propose to use these control
      values as a tool for diagnosing patients with pulmonary complications after LTX
      and for the follow-up of treatment regimens.

PMID- 11850345
TI  - Particulate matter contamination of intravenous antibiotics aggravates loss of
      functional capillary density in postischemic striated muscle.
AB  - Through the increased use of less expensive and counterfeit medicines, the
      contamination of parenteral fluids and drugs by particulate matter poses an
      increasing health hazard worldwide. However, the mechanism of action of such
      contamination has never been conclusively demonstrated. We have systemically
      injected the particles contained in three different 1-g preparations of the
      antibiotic cefotaxime into hamsters and visualized the functional capillary
      density in striated skin muscle, using intravital fluorescence microscopy.
      Injection of particles from either of the three preparations did not affect
      capillary perfusion in normal muscle (n = 3 hamsters, each). However, injection
      of particles from two generic drug preparations, but not the original preparation
      or the saline control, significantly reduced capillary perfusion in muscle tissue
      that had previously been exposed to 4 h of pressure-induced ischemia and 2 h of
      reperfusion (n = 9 hamsters per group). Histological sections demonstrated
      birefringent particles mechanically obliterating the microcirculation of the
      striated muscle. The loss of capillary perfusion due to particle injection or
      injection of standardized microspheres was dependent on the extent of
      ischemia/reperfusion-induced muscle injury, with more capillaries lost in the
      more severely compromised muscle areas. These findings suggest that particle
      contaminants may not pose a major threat in intact tissue, but may severely
      compromise tissue perfusion in patients with prior microvascular compromise of
      vital organs (i.e., after trauma, major surgery, or sepsis) and thus predispose
      to complications such as acute respiratory distress syndrome or multiple organ
      failure.

PMID- 11850344
TI  - Screening for lung cancer with low-dose spiral computed tomography.
AB  - Studies suggest that screening with spiral computed tomography can detect lung
      cancers at a smaller size and earlier stage than chest radiography can. To
      evaluate low-radiation-dose spiral computed tomography and sputum cytology in
      screening for lung cancer, we enrolled 1,520 individuals aged 50 yr or older who
      had smoked 20 pack-years or more in a prospective cohort study. One year after
      baseline scanning, 2,244 uncalcified lung nodules were identified in 1,000
      participants (66%). Twenty-five cases of lung cancer were diagnosed (22
      prevalence, 3 incidence). Computed tomography alone detected 23 cases; sputum
      cytology alone detected 2 cases. Cell types were: squamous cell, 6;
      adenocarcinoma or bronchioalveolar, 15; large cell, 1; small cell, 3. Twenty-two
      patients underwent curative surgical resection. Seven benign nodules were
      resected. The mean size of the non-small cell cancers detected by computed
      tomography was 17 mm (median, 13 mm). The postsurgical stage was IA, 13; IB, 1;
      IIA, 5; IIB, 1; IIIA, 2; limited, 3. Twelve (57%) of the 21 non-small cell
      cancers detected by computed tomography were stage IA at diagnosis. Computed
      tomography can detect early-stage lung cancers. The rate of benign nodule
      detection is high.

PMID- 11850346
TI  - Acute hyperoxic lung injury does not impede adenoviral-mediated alveolar gene
      transfer.
AB  - The transfer of protective genes to the alveolar epithelium can attenuate lung
      injury if accomplished before its onset. The pathobiology of acute lung injury
      (ALI) includes formidable hurdles to gene transfer, including alveoli filled with
      fluid, inflammatory cells, and cytokines, all of which may impair gene transfer
      after the onset of injury. We tested the hypothesis that adenovectors could
      efficiently transduce injured alveoli by exposing adult, male Sprague-Dawley rats
      to 100% oxygen for 48 or 60 h before endotracheal instillation of either 1 x
      10(9) or 4 x 10(9) plaque-forming units of an adenovirus that expresses an
      Escherichia coli lac Z gene (adbeta-gal) in a surfactant-based vehicle
      (Survanta). X-gal staining 72 h postinfection revealed transgene expression in
      all segments of room air control and hyperoxic lungs infected with either dose of
      adbeta-gal. Net transgene expression in hyperoxic lungs was not different from
      room air controls despite the presence of pulmonary edema and severe histologic
      injury. These findings show that adenovectors can efficiently transduce the
      alveoli of acutely injured, edematous lungs. The data indicate that the
      pathophysiologic processes of ALI do not impair adenoviral-mediated alveolar gene
      transfer and provide support for the development of gene therapies for ALI.

PMID- 11850347
TI  - Crucial role of interleukin-1beta and nitric oxide synthase in silica-induced
      inflammation and apoptosis in mice.
AB  - Crystalline silica stimulates macrophages in vitro to release interleukin-1beta
      (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), and nitric oxide (NO) and
      induces apoptosis of macrophages. Because the fibrogenic potential of a
      particulate paralleled its ability to induce apoptosis in macrophages, we
      investigated the underlying mechanisms by which IL-1beta and NO mediate apoptosis
      and inflammation in murine silicosis. First, we demonstrated that silica induced
      NO production and apoptosis in vitro using the IC-21 macrophage cell line. Both
      NO release and apoptosis could be inhibited by neutralizing anti-IL-1beta
      antibody or the NO synthase (NOS) inhibitor N(G)-nitro-L-arginine-methyl ester (L
      NAME), demonstrating the requirement for IL-1beta-mediated NO release in silica
      induced apoptosis. We exposed IL-1beta knockout (IL-1beta(-/-)) mice, inducible
      NOS knockout (iNOS(-/-)) mice, and wild-type mice to 250 mg/m(3) silica for 5 h/d
      for 10 d using an inhalation chamber. Exposure of wild-type mice to silica
      resulted in lung inflammation, apoptosis, and significantly larger and more
      numerous silicotic lesions than in IL-1beta(-/-) mice over a 12-wk course. We
      also exposed iNOS(-/-) mice via inhalation in the same protocol and compared with
      wild-type mice and demonstrated that iNOS(-/-) mice had significantly reduced
      apoptosis and inflammation. These results demonstrated an association between
      apoptosis and inflammation in murine silicosis and support a potential role for
      IL-1beta-dependent NO-mediated apoptosis in the evolution of silicosis.

PMID- 11850348
TI  - Chemokine RANTES in severe pulmonary arterial hypertension.
AB  - The recent discovery that sporadic and familial primary pulmonary hypertension
      can be associated with germline mutations of genes encoding receptor members of
      the transforming growth factor-beta family has focused much attention on
      cytokines and growth factors in pulmonary vascular disorders. Production of
      several cytokines has been demonstrated in severe pulmonary arterial
      hypertension, emphasizing the possible influence of inflammatory mechanisms in
      this condition. Moreover, perivascular inflammatory cell infiltrates composed of
      macrophages and lymphocytes have been detected in plexiform lesions of primary
      pulmonary hypertension. Chemokine RANTES is an important chemoattractant for
      monocytes and T cells. We therefore hypothesize that chemokine RANTES promotes
      cell recruitment in the lungs of patients displaying severe pulmonary arterial
      hypertension. Reverse transcriptase polymerase chain reaction demonstrated
      elevated RANTES mRNA expression in 10 lung samples from patients with severe
      pulmonary arterial hypertension, as compared with seven control subjects. In situ
      hybridization and immunohistochemistry confirmed that endothelial cells were the
      major source of RANTES within the pulmonary artery wall of the patients. Serial
      sections analysis showed that RANTES expression was associated with CD45+
      inflammatory cell infiltrates. These results support the concept that
      inflammatory mechanisms play a role in the natural history of pulmonary arterial
      hypertension.

PMID- 11850349
TI  - Understanding costs and cost-effectiveness in critical care: report from the
      second American Thoracic Society workshop on outcomes research.
AB  - Economic evaluations are increasingly common in the critical care literature,
      although approaches to their conduct are not standardized. The American Thoracic
      Society convened a workshop to address methodologic and reporting issues for
      economic analyses in critical care and to determine how guidelines from the U.S.
      Public Health Service Panel on Cost-effectiveness in Health and Medicine (PCEHM)
      were applicable to critical care. We identified several issues that hamper cost
      effectiveness analyses (CEAs) in the critically ill. Data on the effectiveness of
      intensive care unit (ICU) interventions are often lacking; ICU patients are
      complex, with multiple concurrent problems and interventions; most ICU therapies
      are only supportive, and therefore may not individually result in improved
      outcome; accurate cost data are not commonly available and are difficult to
      obtain; there is no standardized approach for measuring or valuing costs across
      countries; typical outcomes in ICU studies (e.g., short-term mortality) are not
      ideal for CEAs while preferred outcomes for CEAs (e.g., long-term quality
      adjusted survival) are rarely collected; valuing the importance of appropriate
      end-of-life care, an important aspect of ICU care, is difficult, and the burden
      of critical illness on family members is not easily captured in a CEA.
      Nevertheless, many of these problems are not unique to critical care, and we
      believe the PCEHM guidelines can be adapted to the critical care setting. We
      recommend all CEAs in the critically ill include a PCEHM reference case, where
      the cost-effectiveness ratio is calculated by adopting a societal perspective,
      estimating long-term costs and quality of life after ICU care, applying a 3%
      annual discount rate to costs and effects, and conducting multiway sensitivity
      analyses. Because elements of the reference case, such as long-term costs and
      quality of life, may only be estimated using modeling and assumptions, we also
      recommend inclusion of a "data-rich" case, where the cost-effectiveness ratio is
      generated as closely as possible from data on actual patient outcomes and costs
      (e.g., hospital costs per hospital survivor). We recommend that investigators
      conducting a CEA concurrently with a randomized trial make the proposed model
      available (e.g., via the Internet) before unblinding of trial data to minimize
      bias. Adopting a standard approach to CEAs of ICU therapies will provide a valid
      and more transparent evidence base for health care policy with regard to care of
      the critically ill.

PMID- 11850350
TI  - Computed tomography assessment of positive end-expiratory pressure-induced
      alveolar recruitment in patients with acute respiratory distress syndrome.

PMID- 11850351
TI  - Possible dual effect of CD14 molecule on atopy.

PMID- 11850352
TI  - Meretricious effects of coal dust.

PMID- 11850354
TI  - Thoracic surgery in a crisis.

PMID- 11850353
TI  - Hip protectors.

PMID- 11850355
TI  - Was it a heart attack?

PMID- 11850356
TI  - Regulating the regulators.

PMID- 11850357
TI  - BMJ journals free to the developing world.

PMID- 11850358
TI  - Contraception endangered by legal challenge to emergency pill.

PMID- 11850359
TI  - Drug therapy reduces birth rate of HIV infected babies from 19% to 3%.

PMID- 11850361
TI  - Campaigners fear that Russia's new tobacco law won't work.

PMID- 11850362
TI  - Europe moving at the speed of its slowest member in controlling tobacco.

PMID- 11850363
TI  - Government launches intensive media campaign on MMR.

PMID- 11850365
TI  - Netherlands considers prescribing heroin to addicts.

PMID- 11850366
TI  - Parents' champion or loose cannon?

PMID- 11850367
TI  - Effects of a medical emergency team on reduction of incidence of and mortality
      from unexpected cardiac arrests in hospital: preliminary study.
AB  - OBJECTIVES: To determine whether earlier clinical intervention by a medical
      emergency team prompted by clinical instability in a patient could reduce the
      incidence of and mortality from unexpected cardiac arrest in hospital. DESIGN: A
      non-randomised, population based study before (1996) and after (1999)
      introduction of the medical emergency team. SETTING: 300 bed tertiary referral
      teaching hospital. PARTICIPANTS: All patients admitted to the hospital in 1996
      (n=19 317) and 1999 (n=22 847). INTERVENTIONS: Medical emergency team (two
      doctors and one senior intensive care nurse) attended clinically unstable
      patients immediately with resuscitation drugs, fluid, and equipment. Response
      activated by the bedside nurse or doctor according to predefined criteria. MAIN
      OUTCOME MEASURES: Incidence and outcome of unexpected cardiac arrest. RESULTS:
      The incidence of unexpected cardiac arrest was 3.77 per 1000 hospital admissions
      (73 cases) in 1996 (before intervention) and 2.05 per 1000 admissions (47 cases)
      in 1999 (after intervention), with mortality being 77% (56 patients) and 55% (26
      patients), respectively. After adjustment for case mix the intervention was
      associated with a 50% reduction in the incidence of unexpected cardiac arrest
      (odds ratio 0.50, 95% confidence interval 0.35 to 0.73). CONCLUSIONS: In
      clinically unstable inpatients early intervention by a medical emergency team
      significantly reduces the incidence of and mortality from unexpected cardiac
      arrest in hospital.

PMID- 11850368
TI  - Risk adjustment for hospital use using social security data: cross sectional
      small area analysis.
AB  - OBJECTIVES: To identify demographic and socioeconomic determinants of need for
      acute hospital treatment at small area level. To establish whether there is a
      relation between poverty and use of inpatient services. To devise a risk
      adjustment formula for distributing public funds for hospital services using, as
      far as possible, variables that can be updated between censuses. DESIGN: Cross
      sectional analysis. Spatial interactive modelling was used to quantify the
      proximity of the population to health service facilities. Two stage weighted
      least squares regression was used to model use against supply of hospital and
      community services and a wide range of potential needs drivers including health,
      socioeconomic census variables, uptake of income support and family credit, and
      religious denomination. SETTING: Northern Ireland. MAIN OUTCOME MEASURE:
      Intensity of use of inpatient services. RESULTS: After endogeneity of supply and
      use was taken into account, a statistical model was produced that predicted use
      based on five variables: income support, family credit, elderly people living
      alone, all ages standardised mortality ratio, and low birth weight. The main
      effect of the formula produced is to move resources from urban to rural areas.
      CONCLUSIONS: This work has produced a population risk adjustment formula for
      acute hospital treatment in which four of the five variables can be updated
      annually rather than relying on census derived data. Inclusion of the social
      security data makes a substantial difference to the model and to the results
      produced by the formula.

PMID- 11850370
TI  - Socioeconomic differences in Swedish children and adolescents injured in road
      traffic incidents: cross sectional study.

PMID- 11850369
TI  - Measles, mumps, and rubella vaccination and bowel problems or developmental
      regression in children with autism: population study.
AB  - OBJECTIVES: To investigate whether measles, mumps, and rubella (MMR) vaccination
      is associated with bowel problems and developmental regression in children with
      autism, looking for evidence of a "new variant" form of autism. DESIGN:
      Population study with case note review linked to independently recorded vaccine
      data. SETTING: Five health districts in north east London. PARTICIPANTS: 278
      children with core autism and 195 with atypical autism, mainly identified from
      computerised disability registers and born between 1979 and 1998. MAIN OUTCOME
      MEASURES: Recorded bowel problems lasting at least three months, age of reported
      regression of the child's development where it was a feature, and relation of
      these to MMR vaccination. RESULTS: The proportion of children with developmental
      regression (25% overall) or bowel symptoms (17%) did not change significantly (P
      value for trend 0.50 and 0.47, respectively) during the 20 years from 1979, a
      period which included the introduction of MMR vaccination in October 1988. No
      significant difference was found in rates of bowel problems or regression in
      children who received the MMR vaccine before their parents became concerned about
      their development (where MMR might have caused or triggered the autism with
      regression or bowel problem), compared with those who received it only after such
      concern and those who had not received the MMR vaccine. A possible association
      between non-specific bowel problems and regression in children with autism was
      seen but this was unrelated to MMR vaccination. CONCLUSIONS: These findings
      provide no support for an MMR associated "new variant" form of autism with
      developmental regression and bowel problems, and further evidence against
      involvement of MMR vaccine in the initiation of autism.

PMID- 11850371
TI  - Prenatal growth, subsequent marital status, and mortality: longitudinal study.

PMID- 11850372
TI  - What is the role of walk-in centres in the NHS?

PMID- 11850373
TI  - Rhinitis.

PMID- 11850374
TI  - Use of patients in professional medical examinations: current UK practice and the
      ethicolegal implications for medical education.

PMID- 11850375
TI  - The death of the long case?

PMID- 11850377
TI  - ABC of clinical electrocardiography.Introduction. I-Leads, rate, rhythm, and
      cardiac axis.

PMID- 11850376
TI  - Breast cancer.

PMID- 11850378
TI  - What to do about poor clinical performance in clinical trials.

PMID- 11850379
TI  - Rapid assessment of chest pain. "Casualty" is outdated term for "emergency
      medicine".

PMID- 11850380
TI  - Wrong biochemistry results. Companies and Medical Devices Agency must act to
      prevent wrong results.

PMID- 11850381
TI  - Monitoring safety of over the counter drugs. Patients could do more than just
      treat themselves.

PMID- 11850382
TI  - Daily regimen and compliance with treatment. All available evidence needs to be
      evaluated.

PMID- 11850383
TI  - Screening for diabetes in general practice. Opportunistic screening for diabetes
      in general practice is better than nothing.

PMID- 11850384
TI  - Don't strangle health promotion, redefine it.

PMID- 11850385
TI  - School based intervention has reduced obesity in Singapore.

PMID- 11850386
TI  - National guidance and allocation of resources. Acting chairman of SIGN's
      response.

PMID- 11850388
TI  - GPs' undocumented work has increased substantially.

PMID- 11850389
TI  - Children are at risk from parked cars.

PMID- 11850396
TI  - Boundary-independent polar nonsense-mediated decay.
AB  - Nonsense-mediated decay (NMD) is an RNA surveillance mechanism that degrades
      mRNAs containing premature termination (nonsense) codons. The second signal for
      this pathway in mammalian cells is an intron that must be at least approximately
      55 nucleotides downstream of the nonsense codon. Although the functional
      significance of this '-55 boundary rule' is not known, it is widely thought to
      reflect the important role of an exon junction protein complex deposited just
      upstream of exon-exon junctions after RNA splicing. Here we report that a T-cell
      receptor (TCR)-beta gene did not conform to this rule. Rather than a definitive
      boundary position, nonsense codons had a polar effect, such that nonsense codons
      distant from the terminal downstream intron triggered robust NMD and proximal
      nonsense codons caused modest NMD. We identified a region of the TCR-beta gene
      that conferred this boundary-independent polar expression pattern on a
      heterologous gene. Collectively, our results suggest that TCR-beta transcripts
      contain one or more sequence elements that elicit an unusual NMD response
      triggered by a novel second signal that ultimately causes boundary-independent
      polar regulation. TCR genes may have evolved this unique NMD response because
      they frequently acquire nonsense codons during normal development.

PMID- 11850397
TI  - Disruption of Brca2 increases the spontaneous mutation rate in vivo: synergism
      with ionizing radiation.
AB  - The breast cancer predisposition gene BRCA2 encodes a protein involved in the
      repair of DNA double-strand breaks, which arise spontaneously and following
      exposure to ionizing radiation (IR). To develop a mouse model that examines the
      effect of BRCA2 mutation and IR exposure on in vivo somatic mutation acquisition,
      we crossed mice with targeted disruption of Brca2 with a LacZ transgenic mutation
      reporter strain. Loss of both wild-type Brca2 alleles caused a 2.3-fold increase,
      equivalent to an extra 100 mutations per cell, in the in vivo acquisition of
      spontaneous somatic mutation by 2 weeks gestation. IR (4 Gy) had a
      disproportionate effect on animals homozygous for Brca2 disruption, inducing 3.4
      fold more mutations compared with wild-type animals. These data provide the first
      evidence that loss of Brca2 increases in vivo somatic mutation acquisition and
      synergizes with IR exposure, with potential attendant implications for
      mammographic screening and therapeutic IR in mutation carriers.

PMID- 11850398
TI  - GyrI: a counter-defensive strategy against proteinaceous inhibitors of DNA
      gyrase.
AB  - DNA gyrase is the target of two plasmid-encoded toxins CcdB and microcin B17,
      which ensure plasmid maintenance. These proteins stabilize gyrase-DNA covalent
      complexes leading to double-strand breaks in the genome. In contrast, the
      physiological role of chromosomally encoded inhibitor of DNA gyrase (GyrI) in
      Escherichia coli is unclear and its mechanism of inhibition has not been
      established. We demonstrate that the mode of inhibition of GyrI is distinct from
      all other gyrase inhibitors. It inhibits DNA gyrase prior to, or at the step of,
      binding of DNA by the enzyme. GyrI reduces intrinsic as well as toxin-stabilized
      gyrase-DNA covalent complexes. Furthermore, GyrI reduces microcin B17-mediated
      double-strand breaks in vivo, imparting protection to the cells against the
      toxin, substantiating the in vitro results. Thus, GyrI is an antidote to DNA
      gyrase-specific proteinaceous poisons encoded by plasmid addiction systems.

PMID- 11850400
TI  - Involvement of state transitions in the switch between linear and cyclic electron
      flow in Chlamydomonas reinhardtii.
AB  - The energetic metabolism of photosynthetic organisms is profoundly influenced by
      state transitions and cyclic electron flow around photosystem I. The former
      involve a reversible redistribution of the light-harvesting antenna between
      photosystem I and photosystem II and optimize light energy utilization in
      photosynthesis whereas the latter process modulates the photosynthetic yield. We
      have used the wild-type and three mutant strains of the green alga Chlamydomonas
      reinhardtii--locked in state I (stt7), lacking the photosystem II outer antennae
      (bf4) or accumulating low amounts of cytochrome b6f complex (A-AUU)--and measured
      electron flow though the cytochrome b6f complex, oxygen evolution rates and
      fluorescence emission during state transitions. The results demonstrate that the
      transition from state 1 to state 2 induces a switch from linear to cyclic
      electron flow in this alga and reveal a strict cause-effect relationship between
      the redistribution of antenna complexes during state transitions and the onset of
      cyclic electron flow.

PMID- 11850399
TI  - Human MRE11 is inactivated in mismatch repair-deficient cancers.
AB  - Mutations of the ATM and NBS1 genes are responsible for the inherited Ataxia
      Telangiectasia and Nijmegen Breakage Syndrome, both of which are associated with
      a predisposition to cancer. A related syndrome, the Ataxia-Telangiectasia-like
      disorder, is due to mutations of the MRE11 gene. However, the role of this gene
      in cancer development has not been established. Here we describe an often
      homozygous mutation of the poly(T)11 repeat within human MRE11 intron 4 that
      leads to aberrant splicing, impairment of wild-type MRE11 expression and
      generation of a truncated protein. This mutation is present in mismatch repair
      deficient, but not proficient, colorectal cancer cell lines and primary tumours
      and is associated with reduced expression of the MRE11--NBS1--RAD50 complex, an
      impaired S-phase checkpoint and abrogation of MRE11 and NBS1 ionizing radiation
      induced nuclear foci. Our findings identify MRE11 as a novel and major target for
      inactivation in mismatch repair-defective cells and suggest its impairment may
      contribute to the development of colorectal cancer.

PMID- 11850401
TI  - A heterochromatin protein 1 homologue in Caenorhabditis elegans acts in germline
      and vulval development.
AB  - Proteins of the highly conserved heterochromatin protein 1 (HP1) family have been
      found to function in the dynamic organization of nuclear architecture and in gene
      regulation throughout the eukaryotic kingdom. In addition to being key players in
      heterochromatin-mediated gene silencing, HP1 proteins may also contribute to the
      transcriptional repression of euchromatic genes via the recruitment to specific
      promoters. To investigate the role played by these different activities in
      specific developmental pathways, we identified HP1 homologues in the genome of
      Caenorhabditis elegans and used RNA-mediated interference to study their
      function. We show that one of the homologues, HPL-2, is required for the
      formation of a functional germline and for the development of the vulva by acting
      in an Rb-related pathway. We suggest that, by acting as repressors of gene
      expression, HP1 proteins may fulfil specific functions in both somatic and
      germline differentiation processes throughout development.

PMID- 11850402
TI  - PABP1 identified as an arginine methyltransferase substrate using high-density
      protein arrays.
AB  - The arginine methyltransferases CARM1 and PRMT1 associate with the p160 family of
      nuclear hormone receptor coactivators. This association enhances transcriptional
      activation by nuclear receptors. We describe a method for identifying arginine N
      methyltransferase substrates using arrayed high-density protein membranes to
      perform solid-phase supported enzyme reactions in the presence of the methyl
      donor S-adenosyl-l-methionine. Using this screen, we identified distinct
      substrates for CARM1 and PRMT1. All PRMT1 substrates harbor the expected GGRGG
      methylation motif, whereas the peptide sequence comparisons of the CARM1
      substrates revealed no such motif. The predominant CARM1 substrate identified in
      this screen was PABP1. We mapped the methylated region of this RNA binding
      molecule in vitro and demonstrate that PABP1 is indeed methylated in vivo. Prior
      to these findings, the only known substrate for CARM1 was histone H3. We broaden
      the number of CARM1 targets and suggest a role for CARM1 in regulating
      transcription/translation.

PMID- 11850403
TI  - The ABCs of SMC proteins: two-armed ATPases for chromosome condensation,
      cohesion, and repair.

PMID- 11850404
TI  - Template boundary definition in Tetrahymena telomerase.
AB  - Telomerase elongates chromosome ends by addition of telomeric DNA repeats. The
      telomerase ribonucleoprotein can copy only a short template sequence within the
      telomerase RNA subunit. Here, we identify a region of telomerase RNA that is
      necessary for both correct 5' template boundary definition and high affinity
      telomerase reverse transcriptase (TERT) interaction. We also demonstrate that
      TERT mutants in the RNA binding domain compromise both 5' boundary definition and
      RNA binding. Our results indicate that sequence-specific interaction of a
      telomerase RNA element with the TERT RNA binding domain, not the active site
      motifs, defines the template boundary.

PMID- 11850405
TI  - Mutual genetic antagonism involving GLI3 and dHAND prepatterns the vertebrate
      limb bud mesenchyme prior to SHH signaling.
AB  - The bHLH transcription factor dHAND is required for establishment of SHH
      signaling by the limb bud organizer in posterior mesenchyme, a step crucial to
      development of vertebrate paired appendages. We show that the transcriptional
      repressor GLI3 restricts dHAND expression to posterior mesenchyme prior to
      activation of SHH signaling in mouse limb buds. dHAND, in turn, excludes anterior
      genes such as Gli3 and Alx4 from posterior mesenchyme. Furthermore, genetic
      interaction of GLI3 and dHAND directs establishment of the SHH/FGF signaling
      feedback loop by restricting the BMP antagonist GREMLIN posteriorly. These
      interactions polarize the nascent limb bud mesenchyme prior to SHH signaling.

PMID- 11850406
TI  - KSR is a scaffold required for activation of the ERK/MAPK module.
AB  - Mechanisms that regulate signal propagation through the ERK/MAPK pathway are
      still poorly understood. Several proteins are suspected to play critical roles in
      this process. One of these is Kinase Suppressor of Ras (KSR), a component
      previously identified in RAS-dependent genetic screens in Drosophila and
      Caenorhabditis elegans. Here, we show that KSR functions upstream of MEK within
      the ERK/MAPK module. In agreement with this, we found that KSR facilitates the
      phosphorylation of MEK by RAF. We further show that KSR associates independently
      with RAF and MEK, and that these interactions lead to the formation of a RAF/MEK
      complex, thereby positioning RAF in close proximity to its substrate MEK. These
      findings suggest that KSR functions as a scaffold that assembles the RAF/MEK
      functional pair.

PMID- 11850407
TI  - Pseudosubstrate regulation of the SCF(beta-TrCP) ubiquitin ligase by hnRNP-U.
AB  - beta-TrCP/E3RS (E3RS) is the F-box protein that functions as the receptor subunit
      of the SCF(beta-TrCP) ubiquitin ligase (E3). Surprisingly, although its two
      recognized substrates, IkappaB(alpha) and beta-catenin, are present in the
      cytoplasm, we have found that E3RS is located predominantly in the nucleus. Here
      we report the isolation of the major E3RS-associated protein, hnRNP-U, an
      abundant nuclear phosphoprotein. This protein occupies E3RS in a specific and
      stoichiometric manner, stabilizes the E3 component, and is likely responsible for
      its nuclear localization. hnRNP-U binding was abolished by competition with a
      pIkappaB(alpha) peptide, or by a specific point mutation in the E3RS WD region,
      indicating an E3-substrate-type interaction. However, unlike pI(kappa)Balpha,
      which is targeted by SCF(beta-TrCP) for degradation, the E3-bound hnRNP-U is
      stable and is, therefore, a pseudosubstrate. Consequently, hnRNP-U engages a
      highly neddylated active SCF(beta-TrCP), which dissociates in the presence of a
      high-affinity substrate, resulting in ubiquitination of the latter. Our study
      points to a novel regulatory mechanism, which secures the localization,
      stability, substrate binding threshold, and efficacy of a specific protein
      ubiquitin ligase.

PMID- 11850408
TI  - IRE1-mediated unconventional mRNA splicing and S2P-mediated ATF6 cleavage merge
      to regulate XBP1 in signaling the unfolded protein response.
AB  - All eukaryotic cells respond to the accumulation of unfolded proteins in the
      endoplasmic reticulum (ER) by signaling an adaptive pathway termed the unfolded
      protein response (UPR). In yeast, a type-I ER transmembrane protein kinase,
      Ire1p, is the proximal sensor of unfolded proteins in the ER lumen that initiates
      an unconventional splicing reaction on HAC1 mRNA. Hac1p is a transcription factor
      required for induction of UPR genes. In higher eukaryotic cells, the UPR also
      induces site-2 protease (S2P)-mediated cleavage of ER-localized ATF6 to generate
      an N-terminal fragment that activates transcription of UPR genes. To elucidate
      the requirements for IRE1alpha and ATF6 for signaling the mammalian UPR, we
      identified a UPR reporter gene that was defective for induction in IRE1alpha-null
      mouse embryonic fibroblasts and S2P-deficient Chinese hamster ovary (CHO) cells.
      We show that the endoribonuclease activity of IRE1alpha is required to splice
      XBP1 (X-box binding protein) mRNA to generate a new C terminus, thereby
      converting it into a potent UPR transcriptional activator. IRE1alpha was not
      required for ATF6 cleavage, nuclear translocation, or transcriptional activation.
      However, ATF6 cleavage was required for IRE1alpha-dependent induction of UPR
      transcription. We propose that nuclear-localized IRE1alpha and cytoplasmic
      localized ATF6 signaling pathways merge through regulation of XBP1 activity to
      induce downstream gene expression. Whereas ATF6 increases the amount of XBP1
      mRNA, IRE1alpha removes an unconventional 26-nucleotide intron that increases
      XBP1 transactivation potential. Both processing of ATF6 and IRE1alpha-mediated
      splicing of XBP1 mRNA are required for full activation of the UPR.

PMID- 11850409
TI  - Transcriptional cosuppression of yeast Ty1 retrotransposons.
AB  - Cosuppression, the silencing of dispersed homologous genes triggered by high copy
      number, may have evolved in eukaryotic organisms to control molecular parasites
      such as viruses and transposons. Ty1 retrotransposons are dispersed gene repeats
      in Saccharomyces cerevisiae, where no cosuppression has been previously observed.
      Ty1 elements are seemingly expressed undeterred to a level as high as 10% of
      total mRNA. Using Ty1-URA3 reporters and negative selection with 5-fluoroorotic
      acid, it is shown that Ty1 genes can undergo transcriptional cosuppression that
      is independent of DNA methylation and polycomb-mediated repression. Expression of
      Ty1-related genes was shown to be in one of two states, the coexpressed state
      with all Ty1-related genes transcribed or the cosuppressed state with all Ty1
      related genes shut off, without uncoordinated or mosaic expression in any
      individual cell. Rapid switches between the two states were observed. A high copy
      number of Ty1 elements was shown to be required for the initiation of Ty1
      homology-dependent gene silencing, implying that Ty1 gene expression is under
      negative feedback control. Ty1 transcriptional repressors facilitated the onset
      of Ty1 cosuppression, and the native Ty1 promoters were required for Ty1
      cosuppression, indicating that Ty1 cosuppression occurs at the transcriptional
      level.

PMID- 11850410
TI  - Set9, a novel histone H3 methyltransferase that facilitates transcription by
      precluding histone tail modifications required for heterochromatin formation.
AB  - A novel histone methyltransferase, termed Set9, was isolated from human cells.
      Set9 contains a SET domain, but lacks the pre- and post-SET domains. Set9
      methylates specifically lysine 4 (K4) of histone H3 (H3-K4) and potentiates
      transcription activation. The histone H3 tail interacts specifically with the
      histone deacetylase NuRD complex. Methylation of histone H3-K4 by Set9 precludes
      the association of NuRD with the H3 tail. Moreover, methylation of H3-K4 impairs
      Suv39h1-mediated methylation at K9 of H3 (H3-K9). The interplay between the Set9
      and Suv39h1 histone methyltransferases is specific, as the methylation of H3-K9
      by the histone methyltransferase G9a was not affected by Set9 methylation of H3
      K4. Our studies suggest that Set9-mediated methylation of H3-K4 functions in
      transcription activation by competing with histone deacetylases and by precluding
      H3-K9 methylation by Suv39h1. Our results suggest that the methylation of histone
      tails can have distinct effects on transcription, depending on its chromosomal
      location, the combination of posttranslational modifications, and the enzyme (or
      protein complex) involved in the particular modification.

PMID- 11850412
TI  - fzr-1 and lin-35/Rb function redundantly to control cell proliferation in C.
      elegans as revealed by a nonbiased synthetic screen.
AB  - We report here a synthetic-lethal screen in Caenorhabditis elegans that overcomes
      a number of obstacles associated with the analysis of functionally redundant
      genes. Using this approach, we have identified mutations that synthetically
      interact with lin-35/Rb, a SynMuv gene and the sole member of the Rb/pocket
      protein family in C. elegans. Unlike the original SynMuv screens, our approach is
      completely nonbiased and can theoretically be applied to any situation in which a
      mutation fails to produce a detectable phenotype. From this screen we have
      identified fzr-1, a gene that synthetically interacts with lin-35 to produce
      global defects in cell proliferation control. fzr-1 encodes the C. elegans
      homolog of Cdh1/Hct1/FZR, a gene product shown in other systems to regulate the
      APC cyclosome. We have also uncovered genetic interactions between fzr-1 and a
      subset of class B SynMuv genes, and between lin-35 and the putative SCF regulator
      lin-23. We propose that lin-35, fzr-1, and lin-23 function redundantly to control
      cell cycle progression through the regulation of cyclin levels.

PMID- 11850414
TI  - Histone H3 lysine 4 methylation disrupts binding of nucleosome remodeling and
      deacetylase (NuRD) repressor complex.
AB  - Histone N-terminal tails are post-translationally modified in many ways. At
      lysine residues, histones can be either acetylated or methylated. Both
      modifications lead to the binding of specific proteins; bromodomain proteins,
      such as GCN5, bind acetyl lysines and the chromodomain protein, HP1, binds methyl
      lysine 9 of histone H3. Here we show that the previously characterized
      transcriptional repressor complex NuRD (nucleosome remodeling and deacetylase)
      binds to the histone H3 N-terminal tail and that methylation at lysine 4, but not
      lysine 9, prevents binding. Given that lysine 4 methylation is found at sites of
      active transcription, these results suggest that a function of lysine 4
      methylation is to disrupt the association of histones with a repressor complex.

PMID- 11850413
TI  - Brachyury proteins regulate target genes through modular binding sites in a
      cooperative fashion.
AB  - Brachyury proteins, a conserved subgroup of the T domain transcription factors,
      specify gut and posterior mesoderm derivatives throughout the animal kingdom. The
      T domain confers DNA-binding properties to Brachyury proteins, but little is
      known how these proteins regulate their target genes. We characterized a direct
      target gene of the Drosophila Brachyury-homolog Brachyenteron. Brachyenteron
      activates the homeobox gene orthopedia in a dose-dependent manner via multiple
      binding sites with the consensus (A/G)(A/T)(A/T)NTN(A/G)CAC(C/T)T. The sites and
      their A/T-rich flanking regions are conserved between D. melanogaster and
      Drosophila virilis. Reporter assays and site-directed mutagenesis demonstrate
      that Brachyenteron binding sites confer in part additive, in part synergistic
      effects on otp transcription levels. This suggests an interaction of
      Brachyenteron proteins on the DNA, which we could map to a conserved motif within
      the T domain. Mouse Brachyury also interacts with Brachyenteron through this
      motif. We further show that the Xenopus and mouse Brachyury homologs activate
      orthopedia expression when expressed in Drosophila embryonic cells. We propose
      that the mechanisms to achieve target gene expression through variable binding
      sites and through defined protein-protein interactions might be conserved for
      Brachyury relatives.

PMID- 11850411
TI  - Knockout of Arabidopsis accelerated-cell-death11 encoding a sphingosine transfer
      protein causes activation of programmed cell death and defense.
AB  - We describe the lethal, recessive accelerated-cell-death11 Arabidopsis mutant
      (acd11). Cell death in acd11 exhibits characteristics of animal apoptosis
      monitored by flow cytometry, and acd11 constitutively expresses defense-related
      genes that accompany the hypersensitive response normally triggered by avirulent
      pathogens. Global transcriptional changes during programmed cell death (PCD) and
      defense activation in acd11 were monitored by cDNA microarray hybridization. The
      PCD and defense pathways activated in acd11 are salicylic acid (SA) dependent,
      but do not require intact jasmonic acid or ethylene signaling pathways. Light is
      required for PCD execution in acd11, as application of an SA-analog to SA
      deficient acd11 induced death in the light, but not in the dark. Epistatic
      analysis showed that the SA-dependent pathways require two regulators of SA
      mediated resistance responses, PAD4 and EDS1. Furthermore, acd11 PR1 gene
      expression, but not cell death, depends on the SA signal tranducer NPR1,
      suggesting that the npr1-1 mutation uncouples resistance responses and cell death
      in acd11. The acd11 phenotype is caused by deletion of the ACD11 gene encoding a
      protein homologous to a mammalian glycolipid transfer protein (GLTP). In contrast
      to GLTP, ACD11 accelerates the transfer of sphingosine, but not of
      glycosphingolipids, between membranes in vitro.

PMID- 11850415
TI  - Purification and characterization of the Schizosaccharomyces pombe origin
      recognition complex: interaction with origin DNA and Cdc18 protein.
AB  - The origin recognition complex (ORC) plays a central role in the initiation of
      DNA replication in eukaryotic cells. It interacts with origins of DNA replication
      in chromosomal DNA and recruits additional replication proteins to form
      functional initiation complexes. These processes have not been well characterized
      at the biochemical level except in the case of Saccharomyces cerevisiae ORC. We
      report here the expression, purification, and initial characterization of
      Schizosaccharomyces pombe ORC (SpORC) containing six recombinant subunits.
      Purified SpORC binds efficiently to the ars1 origin of DNA replication via the
      essential Nterminal domain of the SpOrc4 subunit which contains nine AT-hook
      motifs. Competition binding experiments demonstrated that SpORC binds
      preferentially to DNA molecules rich in AT-tracts, but does not otherwise exhibit
      a high degree of sequence specificity. The complex is capable of binding to
      multiple sites within the ars1 origin of DNA replication with similar affinities,
      indicating that the sequence requirements for origin recognition in S. pombe are
      significantly less stringent than in S. cerevisiae. We have also demonstrated
      that SpORC interacts directly with Cdc18p, an essential fission yeast initiation
      protein, and recruits it to the ars1 origin in vitro. Recruitment of Cdc18p to
      chromosomal origins is a likely early step in the initiation of DNA replication
      in vivo. These data indicate that the purified recombinant SpORC retains at least
      two of its primary biological functions and that it will be useful for the
      eventual reconstitution of the initiation reaction with purified proteins.

PMID- 11850416
TI  - Magnesium inhibits spontaneous and iron-induced aggregation of alpha-synuclein.
AB  - Multiple studies implicate metals in the pathophysiology of neurodegenerative
      diseases. Disturbances in brain iron metabolism are linked with
      synucleinopathies. For example, in Parkinson's disease, iron levels are increased
      and magnesium levels are reduced in the brains of patients. To understand how
      changes in iron and magnesium might affect the pathophysiology of Parkinson's
      disease, we investigated binding of iron to alpha-synuclein, which accumulates in
      Lewy bodies. Using fluorescence of the four tyrosines in alpha-synuclein as
      indicators of metal-related conformational changes in alpha-synuclein, we show
      that iron and magnesium both interact with alpha-synuclein. alpha-Synuclein
      exhibits fluorescence peaks at 310 and 375 nm. Iron lowers both fluorescence
      peaks, while magnesium increases the fluorescence peak only at 375 nm, which
      suggests that magnesium affects the conformation of alpha-synuclein differently
      than iron. Consistent with this hypothesis, we also observe that magnesium
      inhibits alpha-synuclein aggregation, measured by immunoblot, cellulose acetate
      filtration, or thioflavine-T fluorescence. In each of these studies, iron
      increases alpha-synuclein aggregation, while magnesium at concentrations >0.75 mm
      inhibits the aggregation of alpha-synuclein induced either spontaneously or by
      incubation with iron. These data suggest that the conformation of alpha-synuclein
      can be modulated by metals, with iron promoting aggregation and magnesium
      inhibiting aggregation.

PMID- 11850417
TI  - Isolation of a glucosamine-specific kinase, a unique enzyme of Vibrio cholerae.
AB  - We showed previously that chitin catabolism by the marine bacterium Vibrio
      furnissii involves at least three signal transduction systems and many genes,
      several of which were molecularly cloned, and the corresponding proteins were
      characterized. The predicted amino acid sequences of these proteins showed a high
      degree of identity to the corresponding proteins from Vibrio cholerae, whose
      complete genomic sequence has recently been determined. We have therefore
      initiated studies with V. cholerae. We report here a novel ATP-dependent
      glucosamine kinase of V. cholerae encoded by a gene designated gspK. The protein,
      GspK (31.6 kDa), was purified to apparent homogeneity from recombinant
      Escherichia coli. The product of the reaction was shown to be GlcN-6-P by matrix
      assisted laser desorption/ionization-time of flight (MALDI mass spectrometry) and
      NMR. The K(m) values for GlcN, ATP, and MgCl(2) were 0.45, 2.4, and 2.2 mm,
      respectively, and the V(max) values were in the range 180-200 nmol/microg/min
      (approximately 6 nmol/pmol/min). Kinase activity was not observed with any other
      sugar, including: galactosamine, mannosamine, Glc, GlcNAc, GalNAc, mannose, 2
      deoxyglucose, and oligosaccharides of chitosan. The enzyme is also ATP-specific.
      The kinase can be used to specifically determine micro quantities of GlcN in acid
      hydrolysates of glycoconjugates. The physiological function of this enzyme
      remains to be determined.

PMID- 11850418
TI  - Genetic evidence that protease-activated receptors mediate factor Xa signaling in
      endothelial cells.
AB  - The coagulation protease Factor Xa (Xa)(1) triggers a variety of cellular
      responses that may be important for inflammatory reactions to tissue injury.
      Protease-activated receptors (PAR1, PAR2, and PAR4) can mediate Xa signaling in
      heterologous expression systems. However, other candidate Xa receptors have been
      described, and the extent to which one or more PARs account for Xa signaling in
      relevant differentiated cells is unknown. We examined Xa signaling in endothelial
      cells from wild-type and PAR-deficient mice. Wild-type endothelial cells
      responded to agonists for PAR1, PAR2, and PAR4. Relative to wild-type, Xa
      triggered phosphoinositide hydrolysis was reduced by 60-75% in Par2 -/-
      endothelial cells, by 20-30% in Par1 -/- endothelial cells, and by approximately
      90% in Par2 -/- endothelial cells treated with a PAR1 antagonist. Similar results
      were obtained when ERK1/2 phosphorylation was used to assess Xa signaling. Thus
      PAR2 is the main endogenous Xa receptor in these endothelial cell preparations
      and, together, PAR2 and PAR1 appear to account for approximately 90% of
      endothelial Xa signaling. By contrast, in fibroblasts, PAR1 by itself accounted
      for virtually all Xa-induced phosphoinositide hydrolysis. This information is
      critical for the design and interpretation of knockout mouse studies to probe the
      possible roles of Xa signaling in vivo.

PMID- 11850419
TI  - Molecular basis for pacemaker cells in epithelia.
AB  - Intercellular signaling is highly coordinated in excitable tissues such as heart,
      but the organization of intercellular signaling in epithelia is less clear. We
      examined Ca(2+) signaling in hepatoma cells expressing the hepatocyte gap
      junction protein connexin32 (cx32) or the cardiac gap junction protein cx43, plus
      a fluorescently tagged V(1a) vasopressin receptor (V(1a)R). Release of inositol
      1,4,5-trisphosphate (InsP(3)) in wild type cells increased Ca(2+) in the injected
      cell but not in neighboring cells, while the Ca(2+) signal spread to neighbors
      when gap junctions were expressed. Photorelease of caged Ca(2+) rather than
      InsP(3) resulted in a small increase in Ca(2+) that did not spread to neighbors
      with or without gap junctions. However, photorelease of Ca(2+) in cells
      stimulated with low concentrations of vasopressin resulted in a much larger
      increase in Ca(2+), which spread to neighbors via gap junctions. Cells expressing
      tagged V(1a)R similarly had increased sensitivity to vasopressin, and could
      signal to neighbors via gap junctions. Higher concentrations of vasopressin
      elicited Ca(2+) signals in all cells. In cx32 or cx43 but not in wild type cells,
      this signaling was synchronized and began in cells expressing the tagged V(1a)R.
      Thus, intercellular Ca(2+) signals in epithelia are organized by three factors:
      1) InsP(3) must be generated in each cell to support a Ca(2+) signal in that
      cell; 2) gap junctions are necessary to synchronize Ca(2+) signals among cells;
      and 3) cells with relatively increased expression of hormone receptor will
      initiate Ca(2+) signals and thus serve as pacemakers for their neighbors.
      Together, these factors may allow epithelia to act in an integrated, organ-level
      fashion rather than as a collection of isolated cells.

PMID- 11850420
TI  - Molecular dissection of VirB, a key regulator of the virulence cascade of
      Shigella flexneri.
AB  - The VirB protein is a key regulator of virulence gene expression in the
      facultative enteroinvasive pathogen Shigella flexneri. While genetic evidence has
      shown that it is required for activation of transcription of virulence genes
      located on a 230-kb plasmid in this bacterium, hitherto, evidence that VirB is a
      DNA-binding protein has been lacking. Although VirB shows extensive homology to
      proteins involved in plasmid partitioning, it does not resemble any known
      conventional transcription factor. Here we show for the first time that VirB
      binds to the promoter regions of the virulence genes in vivo. We also show that
      VirB forms dimeric and higher oligomeric structures both in vivo and in vitro and
      that this property is independent of DNA binding. The oligomerization activity of
      VirB is distributed over two domains: a leucine zipper-like motif and a carboxyl
      terminal domain likely to form triple coiled structures. VirB possesses a helix
      turn-helix motif, which is required for DNA binding. The amino-terminal domain of
      the protein is also required for DNA binding and virulence gene activation. The
      possibility that VirB requires a co-factor for specific interaction with target
      promoters in vivo is discussed.

PMID- 11850421
TI  - In vivo footprinting of the human 11beta-hydroxysteroid dehydrogenase type 2
      promoter: evidence for cell-specific regulation by Sp1 and Sp3.
AB  - 11beta-Hydroxysteroid dehydrogenase type 2 is selectively expressed in
      aldosterone target tissues, where it confers aldosterone selectivity for the
      mineralocorticoid receptor by inactivating 11beta-hydroxyglucocorticoids with a
      high affinity for the mineralocorticoid receptor. The present investigation aimed
      to elucidate the mechanisms accounting for the rigorous control of the HSD11B2
      gene in humans. Using dimethyl sulfate in vivo footprinting via ligation-mediated
      PCR, we identified potentially important regions for HSD11B2 regulation in human
      cell lines: two GC-rich regions in the first exon (I and II) and two upstream
      elements (III and IV). The footprints suggest a correlation between the extent of
      in vivo protein occupancy at three of these regions (I, II, and III) and the rate
      of HSD11B2 transcription in cells with high (SW620), intermediate (HCD, MCF-7,
      and HK-2), or low HSD11B2 mRNA levels (SUT). Moreover, gel shift assays with
      nuclear extracts from these cell lines revealed that decreased HSD11B2 expression
      is related to a decreased binding activity with oligonucleotides containing the
      putative regulatory elements. Antibody supershifts identified the majority of the
      components of the binding complexes as the transcription factors Sp1 and Sp3.
      Finally, transient transfections with various deletion mutant reporters define
      positive regulatory elements that might account for basal and selective
      expression of 11beta-hydroxysteroid dehydrogenase type 2.

PMID- 11850422
TI  - An open conformation of the Thermus thermophilus gyrase B ATP-binding domain.
AB  - DNA gyrase forms an A(2)B(2) tetramer involved in DNA replication, repair,
      recombination, and transcription in which the B subunit catalyzes ATP hydrolysis.
      The Thermus thermophilus and Escherichia coli gyrases are homologues and present
      the same catalytic activity. When compared with that of the E. coli 43K-5'
      adenylyl-beta,gamma-imidodiphosphate complex, the crystal structure of Gyrase B
      43K ATPase domain in complex with novobiocin, one of the most potent inhibitors
      of gyrase shows large conformational changes of the subdomains within the dimer.
      The stabilization of loop 98-118 closing the active site through dimeric contacts
      and interaction with domain 2 allows to observe novobiocin-protein interactions
      that could not be seen in the 24K-inhibitor complexes. Furthermore, this loop
      adopts a position which defines an "open" conformation of the active site in
      absence of ATP, in contrast with the "closed" conformation adopted upon ATP
      binding. All together, these results indicate how the subdomains may propagate
      conformational changes from the active site and provide crucial information for
      the design of more specific inhibitors.

PMID- 11850423
TI  - Crystal structure of the carbohydrate recognition domain of p58/ERGIC-53, a
      protein involved in glycoprotein export from the endoplasmic reticulum.
AB  - p58/ERGIC-53 is an animal calcium-dependent lectin that cycles between the
      endoplasmic reticulum (ER) and the Golgi complex and appears to act as a cargo
      receptor for a subset of soluble glycoproteins exported from the ER. We have
      determined the crystal structure of the carbohydrate recognition domain (CRD) of
      p58, the rat homologue of human ERGIC-53, to 1.46 A resolution. The fold and
      ligand binding site are most similar to those of leguminous lectins. The
      structure also resembles that of the CRD of the ER folding chaperone calnexin and
      the neurexins, a family of non-lectin proteins expressed on neurons. The CRD
      comprises one concave and one convex beta-sheet packed into a beta-sandwich. The
      ligand binding site resides in a negatively charged cleft formed by conserved
      residues. A large surface patch of conserved residues with a putative role in
      protein-protein interactions and oligomerization lies on the opposite side of the
      ligand binding site. Together with previous functional data, the structure
      defines a new and expanding class of calcium-dependent animal lectins and
      provides a starting point for the understanding of glycoprotein sorting between
      the ER and the Golgi.

PMID- 11850424
TI  - Yeast Rev1 protein is a G template-specific DNA polymerase.
AB  - Rev1 protein of Saccharomyces cerevisiae functions with DNA polymerase zeta in
      mutagenic trans-lesion synthesis. Because of the reported preferential
      incorporation of a C residue opposite an abasic site, Rev1 has been referred to
      as a deoxycytidyltransferase. Here, we use steady-state kinetics to examine
      nucleotide incorporation by Rev1 opposite undamaged and damaged template
      residues. We show that Rev1 specifically inserts a C residue opposite template G,
      and it is approximately 25-, 40-, and 400-fold less efficient at inserting a C
      residue opposite an abasic site, an O(6)-methylguanine, and an 8-oxoguanine
      lesion, respectively. Rev1 misincorporates G, A, and T residues opposite template
      G with a frequency of approximately 10(-3) to 10(-4). Consistent with this
      finding, Rev1 replicates DNA containing a string of Gs in a template-specific
      manner, but it has a low processivity incorporating 1.6 nucleotides per DNA
      binding event on the average. From these observations, we infer that Rev1 is a G
      template-specific DNA polymerase.

PMID- 11850425
TI  - Regulation of PKC alpha activity by C1-C2 domain interactions.
AB  - In this study, the role of interdomain interactions involving the C1 and C2
      domains in the mechanism of activation of PKC was investigated. Using an in vitro
      assay containing only purified recombinant proteins and the phorbol ester, 4 beta
      12-O-tetradecanoylphorbol-13-acetate (TPA), but lacking lipids, it was found that
      PKC alpha bound specifically, and with high affinity, to a alpha C1A-C1B fusion
      protein of the same isozyme. The alpha C1A-C1B domain also potently activated the
      isozyme in a phorbol ester- and diacylglycerol-dependent manner. The level of
      this activity was comparable with that resulting from membrane association
      induced under maximally activating conditions. Furthermore, it was found that
      alpha C1A-C1B bound to a peptide containing the C2 domain of PKC alpha. The alpha
      C1A-C1B domain also activated conventional PKC beta I, -beta II, and -gamma
      isoforms, but not novel PKC delta or -epsilon. PKC delta and -epsilon were each
      activated by their own C1 domains, whereas PKC alpha, -beta I, -beta II, or 
      gamma activities were unaffected by the C1 domain of PKC delta and only slightly
      activated by that of PKC epsilon. PKC zeta activity was unaffected by its own C1
      domain and those of the other PKC isozymes. Based on these findings, it is
      proposed that the activating conformational change in PKC alpha results from the
      dissociation of intra-molecular interactions between the alpha C1A-C1B domain and
      the C2 domain. Furthermore, it is shown that PKC alpha forms dimers via inter
      molecular interactions between the C1 and C2 domains of two neighboring
      molecules. These mechanisms may also apply for the activation of the other
      conventional and novel PKC isozymes.

PMID- 11850426
TI  - Mycobacterium tuberculosis RecA intein possesses a novel ATP-dependent site
      specific double-stranded DNA endonuclease activity.
AB  - Mycobacterium tuberculosis recA harbors an intervening sequence in its open
      reading frame, presumed to encode an endonuclease (PI-MtuI) required for intein
      homing in inteinless recA allele. Although the protein-splicing ability of PI
      MtuI has been characterized, the identification of its putative endonuclease
      activity has remained elusive. To investigate whether PI-MtuI possesses
      endonuclease activity, recA intervening sequence was cloned, overexpressed, and
      purified to homogeneity. Here we show that PI-MtuI bound both single- and double
      stranded DNA with similar affinity but failed to cleave DNA in the absence of
      cofactors. Significantly, PI-MtuI nicked supercoiled DNA in the presence of
      alternative cofactors but required both Mn(2+) and ATP to generate linear double
      stranded DNA. We observed that PI-MtuI was able to inflict a staggered double
      strand break 24 bp upstream of the insertion site in the inteinless recA allele.
      Similar to a few homing endonucleases, DNA cleavage by PI-MtuI was specific with
      an exceptionally long cleavage site spanning 22 bp. The kinetic mechanism of PI
      MtuI promoted cleavage supports a sequential rather than concerted pathway of
      strand cleavage with the formation of nicked double-stranded DNA as an
      intermediate. Together, these results reveal that RecA intein is a novel Mn(2+)
      ATP-dependent double-strand specific endonuclease, which is likely to be
      important for homing process in vivo.

PMID- 11850427
TI  - Maintenance of integrated proviral gene expression requires Brm, a catalytic
      subunit of SWI/SNF complex.
AB  - We show here that murine leukemia virus-based retrovirus vector transgene
      expression is rapidly silenced in human tumor cell lines lacking expression of
      Brm, a catalytic subunit of the SWI/SNF chromatin remodeling complex, even though
      these vectors can successfully enter, integrate, and initiate transcription. We
      detected this gene silencing as a reduction in the ratio of cells expressing the
      exogenous gene rather than a reduction in the average expression levels,
      indicating that down-regulation occurs in an all-or-none manner. Retroviral gene
      expression was protected from silencing and maintained in Brm-deficient host
      cells by exogenous expression of Brm but not BRG1, an alternative ATPase subunit
      in the SWI/SNF complex. Introduction of exogenous Brm to these cells suppressed
      recruitment of protein complexes containing YY1 and histone deacetylase (HDAC) 1
      and 2 to the 5'-long terminal repeat region of the integrated provirus, leading
      to the enhancement of acetylation of specific lysine residues in histone H4
      located in this region. Consistent with these observations, treatment of Brm
      deficient cells with HDAC inhibitors but not DNA methylation inhibitors
      suppressed retroviral gene silencing. These results suggest that the Brm
      containing SWI/SNF complex subfamily (trithorax-G) and a complex including YY1
      and HDACs (Polycomb-G) counteract each other to maintain transcription of
      exogenously introduced genes.

PMID- 11850428
TI  - Orientation of bound ligands in mannose-binding proteins. Implications for
      multivalent ligand recognition.
AB  - Mannose-binding proteins (MBPs) are C-type animal lectins that recognize high
      mannose oligosaccharides on pathogenic cell surfaces. MBPs bind to their
      carbohydrate ligands by forming a series of Ca(2+) coordination and hydrogen
      bonds with two hydroxyl groups equivalent to the 3- and 4-OH of mannose. In this
      work, the determinants of the orientation of sugars bound to rat serum and liver
      MBPs (MBP-A and MBP-C) have been systematically investigated. The crystal
      structures of MBP-A soaked with monosaccharides and disaccharides and also the
      structure of the MBP-A trimer cross-linked by a high mannose asparaginyl
      oligosaccharide reveal that monosaccharides or alpha1-6-linked mannose bind to
      MBP-A in one orientation, whereas alpha1-2- or alpha1-3-linked mannose binds in
      an orientation rotated 180 degrees around a local symmetry axis relating the 3-
      and 4-OH groups. In contrast, a similar set of ligands all bind to MBP-C in a
      single orientation. The mutation of MBP-A His(189) to its MBP-C equivalent,
      valine, causes Man alpha 1-3Man to bind in a mixture of orientations. These data
      combined with modeling indicate that the residue at this position influences the
      orientation of bound ligands in MBP. We propose that the control of binding
      orientation can influence the recognition of multivalent ligands. A lateral
      association of trimers in the cross-linked crystals may reflect interactions
      within higher oligomers of MBP-A that are stabilized by multivalent ligands.

PMID- 11850429
TI  - Phosphorylation positively regulates DNA binding of the carbon catabolite
      repressor Cre1 of Hypocrea jecorina (Trichoderma reesei).
AB  - Cre1 of the ascomycete Hypocrea jecorina is a Cys(2)His(2) zinc finger DNA
      binding protein functioning as regulator for carbon catabolite repression. It
      represents the functional equivalent of yeast Mig1, known to be negatively
      regulated by the Snf1-kinase at the nuclear import level. We demonstrate that
      Cre1 is also a phosphoprotein, and identify Ser(241) within an acidic protein
      region as phosphorylation target. In contrast to Mig1 phosphorylation is required
      for DNA binding of Cre1. A S241E mutation mimics phosphorylation, whereas a S241A
      mutant protein shows phosphorylation-independent DNA binding activity, suggesting
      that phosphorylation is required to release Cre1 from an inactive conformation
      involving unphosphorylated Ser(241). Retransformation of a H. jecorina cre1-non
      functional mutant with Cre1-S241A leads to permanent carbon catabolite repression
      in cellobiohydrolase I expression. Contrary to Mig1, the amino acid sequence
      surrounding Ser(241) (HSNDEDD) suggests that phosphorylation may occur by a
      casein kinase II-like protein. This is supported by a mutation of E244V leading
      to loss of phosphorylation, loss of DNA binding, and gain of carbon catabolite
      derepression. Our results imply that the regulation of carbon catabolite
      repression at the level of DNA binding strongly differs between Saccharomyces
      cerevisiae and H. jecorina.

PMID- 11850430
TI  - Crystallographic studies of the Escherichia coli quinol-fumarate reductase with
      inhibitors bound to the quinol-binding site.
AB  - The quinol-fumarate reductase (QFR) respiratory complex of Escherichia coli is a
      four-subunit integral-membrane complex that catalyzes the final step of anaerobic
      respiration when fumarate is the terminal electron acceptor. The membrane-soluble
      redox-active molecule menaquinol (MQH(2)) transfers electrons to QFR by binding
      directly to the membrane-spanning region. The crystal structure of QFR contains
      two quinone species, presumably MQH(2), bound to the transmembrane-spanning
      region. The binding sites for the two quinone molecules are termed Q(P) and Q(D),
      indicating their positions proximal (Q(P)) or distal (Q(D)) to the site of
      fumarate reduction in the hydrophilic flavoprotein and iron-sulfur protein
      subunits. It has not been established whether both of these sites are
      mechanistically significant. Co-crystallization studies of the E. coli QFR with
      the known quinol-binding site inhibitors 2-heptyl-4-hydroxyquinoline-N-oxide and
      2-[1-(p-chlorophenyl)ethyl] 4,6-dinitrophenol establish that both inhibitors
      block the binding of MQH(2) at the Q(P) site. In the structures with the
      inhibitor bound at Q(P), no density is observed at Q(D), which suggests that the
      occupancy of this site can vary and argues against a structurally obligatory role
      for quinol binding to Q(D). A comparison of the Q(P) site of the E. coli enzyme
      with quinone-binding sites in other respiratory enzymes shows that an acidic
      residue is structurally conserved. This acidic residue, Glu-C29, in the E. coli
      enzyme may act as a proton shuttle from the quinol during enzyme turnover.

PMID- 11850431
TI  - ATPase domain of eukaryotic DNA topoisomerase II. Inhibition of ATPase activity
      by the anti-cancer drug bisdioxopiperazine and ATP/ADP-induced dimerization.
AB  - We have prepared full-length Drosophila and human topoisomerase II and truncation
      constructs containing the amino-terminal ATPase domain, and we have analyzed
      their biochemical properties. The ATPase activity of the truncation proteins,
      similar to that of the full-length proteins, is greatly stimulated by the
      presence of DNA. This activity of the truncation proteins is also sensitive to
      the inhibition by the drug bisdioxopiperazine, ICRF-193, albeit at a much lower
      level than the full-length protein. Therefore, bisdioxopiperazine can directly
      interact with the NH(2)-terminal ATPase domain, but the drug-enzyme interaction
      may involve other domains as well. The ATPase activity of the ATPase domain
      protein showed a quadratic dependence on enzyme concentration, suggesting that
      dimerization of the NH(2)-terminal domain is a rate-limiting step. Using both
      protein cross-linking and sedimentation equilibrium analysis, we showed that the
      ATPase domain exists as a monomer in the absence of cofactors but can readily
      dimerize in the presence of a nonhydrolyzable analog of ATP, 5'-adenylyl
      beta,gamma-imidodiphosphate. More interestingly, both ATP and ADP can also
      promote protein dimerization. This result thus suggests that the protein clamp,
      mediated through the dimerization of ATPase domain, remains closed after ATP
      hydrolysis and opens upon the dissociation of ADP.

PMID- 11850432
TI  - Fluorescent histochemical techniques for analysis of intracellular signaling.
AB  - Intracellular signaling relies on the orchestrated cooperation of signaling
      proteins and modules, their intracellular localization, and membrane trafficking.
      Recently, a repertoire of fluorescence-based techniques, which significantly
      increases our potential for detailed studies of the involved mechanisms, has been
      introduced. Microscopic techniques with increased resolution have been combined
      with improved techniques for detection of signaling proteins. Transfections of
      fluorescently tagged proteins have allowed in vivo microscopy of their
      trafficking and interactions with other proteins and intracellular structures. We
      present an overview of general signaling principles and a description of
      techniques based on fluorescent microscopy suited for studies of signaling
      mechanisms.

PMID- 11850433
TI  - Immunocytochemical demonstration of the equilibrative nucleoside transporter
      rENT1 in rat sinoatrial node.
AB  - Adenosine exerts multiple receptor-mediated effects in the heart, including a
      negative chronotropic effect on the sinoatrial node. The aim of this study was to
      investigate the distribution of the equilibrative nucleoside transporter rENT1 in
      rat sinoatrial node and atrial muscle. Immunocytochemistry and/or immunoblotting
      revealed abundant expression of this protein in plasma membranes of sinoatrial
      node and in atrial and ventricular cells. Because rENT1-mediated transport is
      likely to regulate the local concentrations of adenosine in the sinoatrial node
      and other parts of the heart, it represents a potential pharmacological target
      that might be exploited to ameliorate ischemic damage during heart surgery.

PMID- 11850434
TI  - Heterogeneous expression of Ca(2+) handling proteins in rabbit sinoatrial node.
AB  - We investigated the densities of the L-type Ca(2+) current, i(Ca,L), and various
      Ca(2+) handling proteins in rabbit sinoatrial (SA) node. The density of i(Ca,L),
      recorded with the whole-cell patch-clamp technique, varied widely in sinoatrial
      node cells. The density of i(Ca,L) was significantly (p<0.001) correlated with
      cell capacitance (measure of cell size) and the density was greater in larger
      cells (likely to be from the periphery of the SA node) than in smaller cells
      (likely to be from the center of the SA node). Immunocytochemical labeling of the
      L-type Ca(2+) channel, Na(+)-Ca(2+) exchanger, sarcoplasmic reticulum Ca(2+)
      release channel (RYR2), and sarcoplasmic reticulum Ca(2+) pump (SERCA2) also
      varied widely in SA node cells. In all cases there was significantly (p<0.05)
      denser labeling of cells from the periphery of the SA node than of cells from the
      center. In contrast, immunocytochemical labeling of the Na(+)-K(+) pump was
      similar in peripheral and central cells. We conclude that Ca(2+) handling
      proteins are sparse and poorly organized in the center of the SA node (normally
      the leading pacemaker site), whereas they are more abundant in the periphery (at
      the border of the SA node with the surrounding atrial muscle).

PMID- 11850435
TI  - Gene expression of MMP8 and MMP13 during embryonic development of bone and
      cartilage in the rat mandible and hind limb.
AB  - Matrix metalloproteinases (MMPs) 8 and 13 comprise the collagenase subfamily in
      rats and mice, and only MMP13 has been implicated in degradation of the
      collagenous matrices during development of bone and cartilage. On the hypothesis
      that MMP8 is also involved in bone and cartilage development, the present study
      was designed to investigate gene expression of MMP8 in rat embryonic mandibles
      and hind limbs. Expression of MMP8 was examined with in situ hybridization and RT
      PCR and was compared with that of MMP13. Osteoblastic and chondrocytic cells
      expressing collagenous matrix molecules were identified using in situ
      hybridization for collagen Types I and II. The results demonstrated that MMP8 is
      expressed by osteoblastic progenitors, differentiated osteoblasts, osteocytes,
      and chondrocytes in the growth plate for the first time. Furthermore, the
      expression of MMP8 is much broader than that of MMP13, for which expression is
      confined to differentiated phenotypes of osteoblastic and chondrocytic lineage.

PMID- 11850436
TI  - Histochemical localization of alkaline phosphatase activity in decalcified bone
      and cartilage.
AB  - We have developed methodology that enables alkaline phosphatase (ALP) to be
      histochemically stained reproducibly in decalcified paraffin-embedded bone and
      cartilage of rodents. Proximal tibiae and fourth lumbar vertebrae were fixed in
      periodate-lysine-paraformaldehyde (PLP) fixative, decalcified in an EDTA-G
      solution, and embedded in paraffin. In the articular cartilage of the proximal
      tibia, ALP activity was localized to the hypertrophic chondrocytes and cartilage
      matrix of the deep zone and the maturing chondrocytes of the intermediate zone.
      The cells and matrix in the superficial zone did not exhibit any enzyme activity.
      In tibial and vertebral growth plates, a progressive increase in ALP expression
      was seen in chondrocytes and cartilage matrix, with activity being weakest in the
      proliferative zone, higher in the maturing zone, and highest in the hypertrophic
      zone. In bone tissue, ALP activity was detected widely in pre-osteoblasts,
      osteoblasts, lining cells on the surface of trabeculae, some newly embedded
      osteocytes, endosteal cells, and subperiosteal cells. In areas of new bone
      formation, ALP activity was detected in osteoid. In the bone marrow, about 20% of
      bone marrow cells expressed ALP activity. In adult rats, the thickness of the
      growth plates was less and ALP activity was enhanced in maturing and hypertrophic
      chondrocytes, cartilage matrix in the hypertrophic zone, and primary spongiosa.
      This is the first time that ALP activity has been successfully visualized
      histochemically in decalcified, paraffin-embedded mineralized tissues. This
      technique should prove to be a very convenient adjunct for studying the behavior
      of osteoblasts during osteogenesis.

PMID- 11850438
TI  - Quantifying the temporospatial expression of postnatal porcine skeletal myosin
      heavy chain genes.
AB  - Postnatal skeletal muscle fiber type is commonly defined by one of four major
      myosin heavy chain (MyHC) gene isoforms (slow/I, 2a, 2x, and 2b) that are
      expressed. We report on the novel use of combined TaqMan quantitative real-time
      RT-PCR and image analysis of serial porcine muscle sections, subjected to in situ
      hybridization (ISH) and immunocytochemistry (IHC), to quantify the mRNA
      expression of each MyHC isoform within its corresponding fiber type, termed
      relative fiber type-restricted expression. This versatile approach will allow
      quantitative temporospatial comparisons of each MyHC isoform among muscles from
      the same or different individuals. Using this approach on porcine skeletal
      muscles, we found that the relative fiber type-restricted expression of each
      postnatal MyHC gene showed wide spatial and temporal variation within a given
      muscle and between muscles. Marked differences were also observed among pig
      breeds. Notably, of the four postnatal MyHC isoforms, the 2a MyHC gene showed the
      highest relative fiber type-restricted expression in each muscle examined,
      regardless of age, breed, or muscle type. This suggests that although 2a fibers
      are a minor fiber type, they may be disproportionately more important as a
      determinant of overall muscle function than was previously believed.

PMID- 11850437
TI  - Evidence of oxidative stress in human corneal diseases.
AB  - This study localized malondialdehyde (MDA, a toxic byproduct of lipid
      peroxidation), nitrotyrosine [NT, a cytotoxic byproduct of nitric oxide (NO)],
      and nitric oxide synthase isomers (NOS) in normal and diseased human corneas.
      Normal corneas (n=11) and those with clinical and histopathological diagnoses of
      keratoconus (n=26), bullous keratopathy (n=17), and Fuchs' endothelial dystrophy
      (n=12) were examined with antibodies specific for MDA, NT, eNOS (constitutive
      NOS), and iNOS (inducible NOS). Normal corneas showed little or no staining for
      MDA, NT, or iNOS, whereas eNOS was detected in the epithelium and endothelium.
      MDA was present in all disease groups, with each group displaying a distinct
      pattern of staining. NT was detected in all keratoconus and approximately one
      half of Fuchs' dystrophy corneas. iNOS and eNOS were evident in all the diseased
      corneas. Keratoconus corneas showed evidence of oxidative damage from cytotoxic
      byproducts generated by lipid peroxidation and the NO pathway. Bullous
      keratopathy corneas displayed byproducts of lipid peroxidation but not
      peroxynitrite (MDA but not NT). Conversely, Fuchs' dystrophy corneas displayed
      byproducts of peroxynitrite with little lipid peroxidation (NT >> MDA). These
      data suggest that oxidative damage occurs within each group of diseased corneas.
      However, each disease exhibits a distinctive profile, with only keratoconus
      showing prominent staining for both nitrotyrosine and MDA. These results suggest
      that keratoconus corneas do not process reactive oxygen species in a normal
      manner, which may play a major role in the pathogenesis of this disease.

PMID- 11850439
TI  - An immunohistochemical approach to monitor the prolactin-induced activation of
      the JAK2/STAT5 pathway in pancreatic islets of Langerhans.
AB  - This study examined whether an immunohistochemical method examining the
      subcellular localization of STAT5 could be used to characterize the activation of
      the JAK2/STAT5 pathway by prolactin (PRL) in intact cells or tissues. In the Ins
      1 beta-cell line, STAT5A and STAT5B were distributed almost equally in the
      cytoplasm and the nucleus in unstimulated cells. STAT5A was also detected along
      the border of cells and in the perinuclear region. After exposure to PRL, the
      redistribution from the cytoplasm to the nucleus was much higher for STAT5B
      compared to STAT5A. This translocation represented 12% of the STAT5A and 22% of
      the STAT5B originally located in the cytoplasm before stimulation. In isolated
      rat islets of Langerhans, PRL stimulated the nuclear translocation of both STAT5A
      and STAT5B only in beta-cells. The expression of the PRL receptor only by beta
      cells was confirmed with a rabbit polyclonal antiserum raised against the rat PRL
      receptor. It was estimated that 4% of STAT5A and 9% of STAT5B originally located
      in the cytoplasm was translocated to the nucleus after stimulation. The presence
      of a functional JAK2/STAT5 signaling pathway in all islet cells was demonstrated
      by the nuclear translocation of STAT5B in all islet cells (i.e., alpha-, beta-,
      and delta-cells) after stimulation with fetal calf serum. The nuclear
      translocation and tyrosine phosphorylation of STAT5B was biphasic, with an
      initial peak within 30 min, a nadir between 1 and 3 hr, and prolonged activation
      after 4 hr. In contrast, the tyrosine phosphorylation of STAT5A was also biphasic
      but its nuclear translocation peaked within 30 min and was then reduced to a
      level slightly above that observed before PRL stimulation. This method is able to
      detect changes in STAT5 activation as small as 2% of the total cell content.
      These observations demonstrate the utility of this approach for studying the
      activation of STAT5 in a mixed population of cells within tissues or organs. In
      addition, the dose response for the nuclear translocation of STAT5B in normal
      beta-cells was similar to those for changes in proliferation and insulin
      secretion in isolated rat islets. Therefore, the subcellular localization can be
      used to monitor the activation of STAT5 and it may be a key event in the
      upregulation of the pancreatic islets of Langerhans during pregnancy.

PMID- 11850440
TI  - Smooth muscle myosin heavy chain isoform distribution in the swine stomach.
AB  - To evaluate the distribution of smooth muscle myosin heavy chain isoforms (SMB,
      with head insert), we examined frozen sections from the various regions of swine
      stomachs using isoform-specific antibodies. We previously reported variable SMB
      myosin heavy chain (MHC) expression in stomach cells that correlates with
      unloaded shortening velocities. This is consistent with the generalization of
      tonic fundic muscle having low expression and phasic antral muscle having high
      expression of the SMB MHC isoform. Using immunohistochemistry (IHC), we show a
      progression of the SMB MHC from very low immunoreactivity in the fundus to very
      intense immunoreactivity in the antrum. In the body, the average level of SMB MHC
      immunoreactivity lies between that of the antrum and fundus. Intercellular
      heterogeneity was observed in all stomach regions to a similar extent. However,
      the intercellular range in SMB MHC immunoreactivity decreases from fundus to
      antrum. All stomach regions show isolated pockets or clusters of cells with
      similar SMB MHC immunoreactivity. There is a non-uniform intracellular
      immunoreactivity in SMB MHC, with many cells showing greater-intensity staining
      of SMB MHC in their cell peripheries. This information may prove useful in
      helping to elucidate possible unique physiological roles of SMB MHC.

PMID- 11850441
TI  - IGF-1 induces foam cell formation in rat glomerular mesangial cells.
AB  - When rat glomerular mesangial cells (MCs) are cultured with IGF-1 they accumulate
      intracellular lipid and take on foam cell morphology. These changes were
      characterized by electron microscopy and Nile red staining. To define the
      mechanism responsible for IGF-1-mediated lipid uptake, MCs were evaluated for
      endocytosis, scavenger receptor activity, and receptor-mediated uptake by the LDL
      receptor. Lipid accumulation was markedly increased when MCs were cultured with
      IGF. The primary route of uptake was through enhanced endocytosis. Lipid-laden
      MCs have decreased phagocytic capacity and disrupted cytoskeletons. These data
      show that IGF-1 induces MC to take on a foam cell morphology and that lipid-laden
      MCs have impaired phagocytic function.

PMID- 11850442
TI  - Cytochemical and biochemical demonstration of an ATPase in membranes of human
      peroxisomes.
AB  - We demonstrated a neutral Mg-ATPase activity in human peroxisomal membranes. To
      establish the precise experimental conditions for detection of this ATPase, both
      cytochemical and biochemical characterizations were first carried out in liver
      peroxisomes from control and cipofibrate-treated rats. The results demonstrated
      an Mg-ATPase reaction in both normal and proliferated peroxisomes. The
      nucleotidase activity, with marked preference for ATP, was sensitive to the
      inhibitors N-ethylmaleimide and 7-chloro-4-nitro-benzo-2-oxadiazole (NBDCl). An
      ultrastructural cytochemical analysis was developed to evaluate the peroxisomal
      localization, which localized the reaction product to the peroxisomal membrane.
      These characteristics can help to differentiate the peroxisomal ATPase from the
      activity found in mitochondria and endoplasmic reticulum. The conditions
      established for detecting the rat peroxisomal ATPase were then applied to human
      peroxisomes isolated from liver and skin fibroblasts in culture. A similar Mg
      ATPase activity was readily shown, both cytochemically and biochemically, in the
      membranes of human peroxisomes. These results, together with previous evidence,
      strongly support the presence of a specific ATPase in the human peroxisomal
      membrane. This ATPase may play a crucial role in peroxisome biogenesis.

PMID- 11850443
TI  - Inhibitor profiles of alkaline phosphatases in bovine preattachment embryos and
      adult tissues.
AB  - The alkaline phosphatases are a small family of isozymes. Bovine preattachment
      embryos transcribe mRNA for two tissue-specific alkaline phosphatases (TSAP2 and
      TSAP3) beginning at the 4- and 8-cell stages. Whereas no mRNA has been detected
      in oocytes, there is maternally inherited alkaline phosphatase activity. It is
      not known which isozyme(s) is responsible for the maternal activity or when TSAP2
      and TSAP3 form functional protein. No antibodies are available that recognize the
      relevant bovine alkaline phosphatases. Therefore, sensitivity to heat and
      chemical inhibition was used to separate the different isozymes. By screening
      tissues, it was determined that the bovine tissue-nonspecific alkaline
      phosphatase (TNAP) is inactivated by low temperatures (65C) and low
      concentrations of levamisole (<1 mM), whereas bovine tissue-specific isozymes
      require higher temperatures (90C) and levamisole concentrations (>5 mM).
      Inhibition by L-homoarginine and L-phenylalanine was less informative. Cumulus
      cells transcribe two isozymes and the pattern of inhibition suggested heterodimer
      formation. Inhibition of alkaline phosphatase in bovine embryos before the 8-cell
      stage indicated the presence of only TNAP. At the 16-cell stage the pattern was
      consistent with TNAP plus TSAP2 or -3 activity, and in morulae and blastocysts
      the pattern indicated that the maternal TNAP is fully supplanted by TSAP2 or
      TSAP3.

PMID- 11850444
TI  - Tenascin-C is highly expressed in respiratory distress syndrome and
      bronchopulmonary dysplasia.
AB  - Tenascin-C is an extracellular matrix (ECM) glycoprotein expressed in human
      tissues during organogenesis and in fibrotic and neoplastic processes. We
      hypothesized that its expression would increase in human lung in neonatal
      disorders such as infant respiratory distress syndrome (RDS) and bronchopulmonary
      dysplasia (BPD). Tenascin-C expression was studied by immunohistochemistry (IHC)
      and mRNA in situ hybridization (ISH). The extent of tenascin-C immunoreactivity
      was scored as absent (0), low (+), moderate (++), strong (+++), or very strong
      (++++) separately in different types of pulmonary cells in controls (seven
      cases), RDS (19 cases), and BPD (12 cases). In controls, tenascin-C expression
      was low (+) underneath alveolar and bronchiolar epithelium, moderate (++) in
      intima of veins, and strong (+++) around chondrocytes. In RDS, tenascin-C
      expression was moderate (++) or strong (+++) underneath both bronchiolar and
      often detached alveolar epithelium underlying hyaline membranes in the walls of
      dilated alveoli. In particular, the patients with RDS who survived for 1 day or
      more had strong expression of tenascin-C within alveolar walls. In patients with
      BPD, tenascin-C was very strongly (++++) expressed in the remodeled fibrotic
      alveolar walls underneath regenerative epithelium. Increased expression of
      tenascin-C mRNA was seen below the alveolar and bronchiolar epithelia in RDS and
      BPD. The cells in these locations showed alpha-smooth muscle actin
      immunoreactivity, suggesting a myofibroblast phenotype. In conclusion, tenascin-C
      is highly expressed in the walls of alveoli and bronchioli in RDS and BPD,
      suggesting an association between the expression of this protein and the presence
      of these disorders.

PMID- 11850445
TI  - Human lipocalin-1, a physiological scavenger of lipophilic compounds, is produced
      by corticotrophs of the pituitary gland.
AB  - Lipocalin-1 (Lcn-1), a member of the lipocalin superfamily that binds a broad
      array of different chemical classes of lipophilic ligands, is believed to act as
      a physiological scavenger of potentially harmful lipophilic molecules. Thus far,
      it was thought to be produced exclusively by a number of exocrine glands and
      tissues, including lachrymal and lingual glands, prostate, secretory glands of
      the tracheobronchial tract, and sweat glands. Using Northern blotting analysis,
      we were able to demonstrate Lcn-1 expression by the human pituitary gland.
      Moreover, double immunolabeling with antibodies against Lcn-1 and pituitary gland
      hormones and detection with fluorophore-conjugated secondary antibodies revealed
      that Lcn-1 is specifically produced by corticotrophs, clearly indicating that its
      distribution is not restricted to exocrine tissues.

PMID- 11850446
TI  - Simple method for reduction of autofluorescence in fluorescence microscopy.
AB  - Autofluorescence of aldehyde-fixed neural tissue often complicates the use of
      fluorescence microscopy. Background fluorescence can be notably reduced or
      eliminated by irradiation with light before treatment with fluorescence probes,
      resulting in a higher contrast without adversely affecting the staining
      probabilities.

PMID- 11850447
TI  - Pathway-specific properties of AMPA and NMDA-mediated transmission in CA1
      hippocampal pyramidal cells.
AB  - CA1 pyramidal cells receive glutamatergic input from the entorhinal cortex
      through the perforant path (PP) and from CA3 through Schaffer collaterals (SC).
      The PP input terminates in the stratum lacunosum molecular approximately 300
      microm from the cell body, whereas SC synapses have a more proximal location in
      the stratum radiatum. We compared the properties of AMPA- and NMDA-mediated
      transmission at these two inputs. The AMPA-mediated components have linear
      voltage dependence in both inputs. The reversal potential in the PP is only
      slightly more positive than in the SC, indicating that distal membrane voltage
      could be effectively set. The NMDA-mediated responses in the two pathways,
      however, are very different. The PP exhibits inward rectification, as evidenced
      by very low outward currents. The rectification persists in the absence of
      extracellular Mg2+. It cannot be attributed to clamping problems, because large
      outward AMPA currents can be observed even when conditions are modified to have
      the AMPA currents kinetically match the NMDA currents. Thus, it appears that the
      PP NMDA channels have novel properties. A second difference between the PP and SC
      pathways is that the PP has a larger NMDA/AMPA charge ratio. This difference
      could be observed under many conditions, including block of all voltage-dependent
      conductances and elimination of the negative resistance of NMDA channels by
      removing extracellular Mg2+. The difference in ratio thus cannot be attributed to
      regenerative currents. The higher NMDA component of the distal PP synapses could
      help to make these synapses more powerful under depolarizing conditions.

PMID- 11850448
TI  - Distribution and pharmacology of alpha 6-containing nicotinic acetylcholine
      receptors analyzed with mutant mice.
AB  - The alpha6 subunit of the nicotinic acetylcholine receptor (nAChR) is expressed
      at very high levels in dopaminergic (DA) neurons. However, because of the lack of
      pharmacological tools selective for alpha6-containing nAChRs, the role of this
      subunit in the etiology of nicotine addiction remains unknown. To provide new
      tools to investigate this issue, we generated an alpha6 nAChR knock-out mouse.
      Homozygous null mutants (alpha6-/-) did not exhibit any gross neurological or
      behavioral deficits. A careful anatomic and molecular examination of alpha6-/-
      mouse brains demonstrated the absence of developmental alterations in these
      animals, especially in the visual and dopaminergic pathways, where the alpha6
      subunit is normally expressed at the highest levels. On the other hand, receptor
      autoradiography revealed a decrease in [3H]nicotine, [3H]epibatidine, and
      [3H]cytisine high-affinity binding in the terminal fields of retinal ganglion
      cells of alpha6-/- animals, whereas high-affinity [125I]alpha-conotoxinMII
      (alphaCtxMII) binding completely disappeared in the brain. Moreover, inhibition
      of [3H]epibatidine binding on striatal membranes, using unlabeled alphaCtxMII or
      cytisine, revealed the absence of alphaCtxMII-sensitive and cytisine-resistant
      [3H]epibatidine binding sites in alpha6-/- mice, although the total amount of
      binding was unchanged. Because alphaCtxMII, a toxin formerly thought to be
      specific for alpha3beta2-containing nAChRs, is known to partially inhibit
      nicotine-induced dopamine release, these results support the conclusion that
      alpha6 rather than alpha3 is the partner of beta2 in the nicotinic modulation of
      DA neurons. They further show that alpha6-/- mice might be useful tools to
      understand the mechanisms of nicotine addiction, although some developmental
      compensation might occur in these mice.

PMID- 11850449
TI  - Inhibition of caspases prevents ototoxic and ongoing hair cell death.
AB  - Sensory hair cells die after acoustic trauma or ototoxic insults, but the signal
      transduction pathways that mediate hair cell death are not known. Here we
      identify several important signaling events that regulate the death of vestibular
      hair cells. Chick utricles were cultured in media supplemented with the ototoxic
      antibiotic neomycin and selected pharmacological agents that influence signaling
      molecules in cell death pathways. Hair cells that were treated with neomycin
      exhibited classically defined apoptotic morphologies such as condensed nuclei and
      fragmented DNA. Inhibition of protein synthesis (via treatment with
      cycloheximide) increased hair cell survival after treatment with neomycin,
      suggesting that hair cell death requires de novo protein synthesis. Finally, the
      inhibition of caspases promoted hair cell survival after neomycin treatment.
      Sensory hair cells in avian vestibular organs also undergo continual cell death
      and replacement throughout mature life. It is unclear whether the loss of hair
      cells stimulates the proliferation of supporting cells or whether the production
      of new cells triggers the death of hair cells. We examined the effects of caspase
      inhibition on spontaneous hair cell death in the chick utricle. Caspase
      inhibitors reduced the amount of ongoing hair cell death and ongoing supporting
      cell proliferation in a dose-dependent manner. In isolated sensory epithelia,
      however, caspase inhibitors did not affect supporting cell proliferation
      directly. Our data indicate that ongoing hair cell death stimulates supporting
      cell proliferation in the mature utricle.

PMID- 11850450
TI  - Activation of central terminal vanilloid receptor-1 receptors and alpha beta
      methylene-ATP-sensitive P2X receptors reveals a converged synaptic activity onto
      the deep dorsal horn neurons of the spinal cord.
AB  - Using a spinal cord slice preparation and patch-clamp recordings from spinal cord
      dorsal horn neurons, we examined excitatory and inhibitory circuits connecting to
      lamina V neurons after the activation of afferent central terminal vanilloid
      receptor-1 (VR1) receptors and P2X receptors. We found that single neurons in
      lamina V often received excitatory inputs from two chemically defined afferent
      pathways. One of these pathways was polysynaptic from capsaicin-sensitive
      afferent terminals. In this pathway the capsaicin-sensitive afferent input first
      activated interneurons in superficial laminas, and then the excitatory activity
      was transmitted onto lamina V neurons. The second excitatory input was
      monosynaptic from alpha(beta)m-ATP-sensitive/capsaicin-insensitive afferent
      terminals. Both capsaicin-sensitive and alpha(beta)m-ATP-sensitive/capsaicin
      insensitive pathways also recruited polysynaptic inhibitory inputs to lamina V
      neurons. Furthermore, we demonstrated that simultaneous activation of both
      capsaicin-sensitive afferent pathways and alpha(beta)m-ATP-sensitive/capsaicin
      insensitive pathways could generate a temporal summation of excitatory inputs
      onto single lamina V neurons. These convergent pathways may provide a mechanism
      of sensory integration for two chemically defined sensory inputs and may have
      implications in different sensory states.

PMID- 11850451
TI  - Mechanosensitive ion channels in cultured sensory neurons of neonatal rats.
AB  - Mechanosensitive (MS) ion channels are present in a variety of cells. However,
      very little is known about the ion channels that account for mechanical
      sensitivity in sensory neurons. We identified the two most frequently encountered
      but distinct types of MS channels in 1390 of 2962 membrane patches tested in
      cultured dorsal root ganglion neurons. The two MS channels exhibited different
      thresholds, thus named as low-threshold (LT) and high-threshold (HT) MS channels,
      and sensitivity to pressure. The two channels retained different single-channel
      conductances and current-voltage relationships: LT and HT channels elicited large
      and small-channel conductance with outwardly rectifying and linear I-V
      relationships, respectively. Both LT and HT MS channels were permeable to
      monovalent cations and Ca2+ and were blocked by gadolinium, a blocker of MS
      channels. Colchicine and cytochalasin D markedly reduced the activities of the
      two MS channels, indicating that cytoskeletal elements support the
      mechanosensitivity. Both types of MS channels were found primarily in small
      sensory neurons with diameters of <30 microm. Furthermore, HT MS channels were
      sensitized by a well known inducer of mechanical hyperalgesia, prostaglandin E2,
      via the protein kinase A pathway. We identified two distinct types of MS channels
      in sensory neurons that probably give rise to the observed MS whole-cell currents
      and transduce mechanical stimuli to neural signals involved in somatosensation,
      including pain.

PMID- 11850452
TI  - Differential desensitization of responses mediated by presynaptic and
      postsynaptic A1 adenosine receptors.
AB  - G-protein-coupled receptors (GPCRs) often desensitize during continuous
      activation, but it is not known whether desensitization is influenced by
      subcellular location. In hippocampal neurons, activation of adenosine A1
      receptors (A1Rs) or GABA(B) receptors on synaptic terminals inhibits
      neurotransmitter release, whereas activation of the same receptors on cell bodies
      and dendrites decreases excitability by activating inwardly rectifying potassium
      (GIRK) channels. Here we report that responses mediated by presynaptic A1Rs
      desensitize more slowly than responses mediated by postsynaptic (somatodendritic)
      A1Rs in cultured neurons. Agonist treatment for 2 hr has no effect on adenosine
      induced presynaptic inhibition, whereas such treatment nearly abolishes adenosine
      induced activation of postsynaptic GIRK channels. Agonist treatment for longer
      periods (>12 hr) eventually desensitizes A1R-mediated presynaptic inhibition.
      Presynaptic and postsynaptic responses both recover from desensitization after
      agonist removal, but recovery of presynaptic inhibition requires more time.
      Desensitization of postsynaptic responses apparently occurs at the level of the
      receptor, because postsynaptic G-proteins and GIRK channels appear to be fully
      functional. Inhibition of voltage-gated calcium channels by postsynaptic A1Rs
      also desensitizes rapidly, although this desensitization is less complete than is
      observed for activation of postsynaptic GIRK channels. Comparison of
      concentration-response curves for presynaptic and postsynaptic responses suggests
      that a receptor reserve exists for presynaptic inhibition, but that the magnitude
      of this reserve is insufficient to account for the absence of presynaptic
      desensitization after brief agonist exposure. These results suggest that agonist
      induced desensitization of responses mediated by neuronal GPCRs may depend on the
      subcellular location of the receptors.

PMID- 11850453
TI  - Serotonergic raphe neurons express TASK channel transcripts and a TASK-like pH-
      and halothane-sensitive K+ conductance.
AB  - The recently described two-pore-domain K+ channels, TASK-1 and TASK-3, generate
      currents with a unique set of properties; specifically, the channels produce
      instantaneous open-rectifier (i.e., "leak") K+ currents that are modulated by
      extracellular pH and by clinically useful anesthetics. In this study, we used
      histochemical and in vitro electrophysiological approaches to determine that TASK
      channels are expressed in serotonergic raphe neurons and to show that they confer
      a pH and anesthetic sensitivity to these neurons. By combining in situ
      hybridization for TASK-1 or TASK-3 with immunohistochemical localization of
      tryptophan hydroxylase, we found that a majority of serotonergic neurons in both
      dorsal and caudal raphe cell groups contain TASK channel transcripts
      (approximately 70-90%). Whole-cell voltage-clamp recordings were obtained from
      raphe cells that responded to 5-HT in a manner characteristic of serotonergic
      neurons (i.e., with activation of an inwardly rectifying K+ current). In those
      cells, we isolated an endogenous K+ conductance that had properties expected of
      TASK channel currents; raphe neurons expressed a joint pH- and halothane
      sensitive open-rectifier K+ current. The pH sensitivity of this current (pK
      approximately 7.0) was intermediate between that of TASK-1 and TASK-3, consistent
      with functional expression of both channel types. Together, these data indicate
      that TASK-1 and TASK-3 are expressed and functional in serotonergic raphe
      neurons. The pH-dependent inhibition of TASK channels in raphe neurons may
      contribute to ventilatory and arousal reflexes associated with extracellular
      acidosis; on the other hand, activation of raphe neuronal TASK channels by
      volatile anesthetics could play a role in their immobilizing and sedative
      hypnotic effects.

PMID- 11850454
TI  - The core membrane fusion complex governs the probability of synaptic vesicle
      fusion but not transmitter release kinetics.
AB  - Synaptic vesicle fusion is driven by the formation of a four-helical bundle
      composed of soluble N-ethylmaleimide sensitive factor (NSF) attachment protein
      receptors (SNAREs). Exactly how the structural interactions that lead to the
      formation of this complex relate to neurotransmitter release is not well
      understood. To address this question, we used a strategy to "rescue" synaptic
      transmission after proteolytic cleavage of the synaptosome-associated protein of
      25 kDa (SNAP-25) by botulinum neurotoxin E (BoNtE). Transfection of CA3
      hippocampal pyramidal cells with BoNtE-resistant SNAP-25 restored synaptic
      transmission. Additional mutations that alter the interaction between SNAP-25 C
      terminal coil and the other SNARE coils dramatically reduce transmitter release
      probability but leave the kinetics of synaptic responses unaltered. These data
      indicate that at synapses, SNARE interactions are necessary for fusion but are
      not the rate-limiting step of neurotransmission.

PMID- 11850455
TI  - Blockade of Ca2+-permeable AMPA/kainate channels decreases oxygen-glucose
      deprivation-induced Zn2+ accumulation and neuronal loss in hippocampal pyramidal
      neurons.
AB  - Synaptic release of Zn2+ and its translocation into postsynaptic neurons probably
      contribute to neuronal injury after ischemia or epilepsy. Studies in cultured
      neurons have revealed that of the three major routes of divalent cation entry,
      NMDA channels, voltage-sensitive Ca2+ channels (VSCCs), and Ca2+-permeable
      AMPA/kainate (Ca-A/K) channels, Ca-A/K channels exhibit the highest permeability
      to exogenously applied Zn2+. However, routes through which synaptically released
      Zn2+ gains entry to postsynaptic neurons have not been characterized in vivo. To
      model ischemia-induced Zn2+ movement in a system approximating the in vivo
      situation, we subjected mouse hippocampal slice preparations to controlled
      periods of oxygen and glucose deprivation (OGD). Timm's staining revealed little
      reactive Zn2+ in CA1 and CA3 pyramidal neurons of slices exposed in the presence
      of O2 and glucose. However, 15 min of OGD resulted in marked labeling in both
      regions. Whereas strong Zn2+ labeling persisted if both the NMDA antagonist MK
      801 and the VSCC blocker Gd3+ were present during OGD, the presence of either the
      Ca-A/K channel blocker 1-naphthyl acetyl spermine (NAS) or the extracellular Zn2+
      chelator Ca2+ EDTA substantially decreased Zn2+ accumulation in pyramidal neurons
      of both subregions. In parallel experiments, slices were subjected to 5 min OGD
      exposures as described above, followed 4 hr later by staining with the cell-death
      marker propidium iodide. As in the Timm's staining experiments, substantial CA1
      or CA3 pyramidal neuronal damage occurred despite the presence of MK-801 and
      Gd3+, whereas injury was decreased by NAS or by Ca2+ EDTA (in CA1).

PMID- 11850456
TI  - Tamalin, a PDZ domain-containing protein, links a protein complex formation of
      group 1 metabotropic glutamate receptors and the guanine nucleotide exchange
      factor cytohesins.
AB  - In this investigation, we report identification and characterization of a 95 kDa
      postsynaptic density protein (PSD-95)/discs-large/ZO-1 (PDZ) domain-containing
      protein termed tamalin, also recently named GRP1-associated scaffold protein
      (GRASP), that interacts with group 1 metabotropic glutamate receptors (mGluRs).
      The yeast two-hybrid system and in vitro pull-down assays indicated that the PDZ
      domain-containing, amino-terminal half of tamalin directly binds to the class I
      PDZ-binding motif of group 1 mGluRs. The C-terminal half of tamalin also bound to
      cytohesins, the members of guanine nucleotide exchange factors (GEFs) specific
      for the ADP-ribosylation factor (ARF) family of small GTP-binding proteins.
      Tamalin mRNA is expressed predominantly in the telencephalic region and highly
      overlaps with the expression of group 1 mGluR mRNAs. Both tamalin and cytohesin-2
      were enriched and codistributed with mGluR1a in postsynaptic membrane fractions.
      Importantly, recombinant and native mGluR1a/tamalin/cytohesin-2 complexes were
      coimmunoprecipitated from transfected COS-7 cells and rat brain tissue,
      respectively. Transfection of tamalin and mutant tamalin lacking a cytohesin
      binding domain caused an increase and decrease in cell-surface expression of
      mGluR1a in COS-7 cells, respectively. Furthermore, adenovirus-mediated expression
      of tamalin and dominant-negative tamalin facilitated and reduced the neuritic
      distribution of endogenous mGluR5 in cultured hippocampal neurons, respectively.
      The results indicate that tamalin plays a key role in the association of group 1
      mGluRs with the ARF-specific GEF proteins and contributes to intracellular
      trafficking and the macromolecular organization of group 1 mGluRs at synapses.

PMID- 11850457
TI  - I(h) channels contribute to the different functional properties of identified
      dopaminergic subpopulations in the midbrain.
AB  - Dopaminergic (DA) midbrain neurons in the substantia nigra (SN) and ventral
      tegmental area (VTA) are involved in various brain functions such as voluntary
      movement and reward and are targets in disorders such as Parkinson's disease and
      schizophrenia. To study the functional properties of identified DA neurons in
      mouse midbrain slices, we combined patch-clamp recordings with either neurobiotin
      cell-filling and triple labeling confocal immunohistochemistry, or single-cell RT
      PCR. We discriminated four DA subpopulations based on anatomical and
      neurochemical differences: two calbindin D28-k (CB)-expressing DA populations in
      the substantia nigra (SN/CB+) or ventral tegmental area (VTA/CB+), and
      respectively, two calbindin D28-k negative DA populations (SN/CB-, VTA/CB-).
      VTA/CB+ DA neurons displayed significantly faster pacemaker frequencies with
      smaller afterhyperpolarizations compared with other DA neurons. In contrast, all
      four DA populations possessed significant differences in I(h) channel densities
      and I(h) channel-mediated functional properties like sag amplitudes and rebound
      delays in the following order: SN/CB- --> VTA/CB- --> SN/CB+ --> VTA/CB+. Single
      cell RT-multiplex PCR experiments demonstrated that differential calbindin but
      not calretinin expression is associated with differential I(h) channel densities.
      Only in SN/CB- DA neurons, however, I(h) channels were actively involved in
      pacemaker frequency control. In conclusion, diversity within the DA system is not
      restricted to distinct axonal projections and differences in synaptic
      connectivity, but also involves differences in postsynaptic conductances between
      neurochemically and topographically distinct DA neurons.

PMID- 11850458
TI  - Small proline-rich repeat protein 1A is expressed by axotomized neurons and
      promotes axonal outgrowth.
AB  - The ability of neurons to regenerate an axon after injury is determined by both
      the surrounding environment and factors intrinsic to the damaged neuron. We have
      used cDNA microarrays to survey those genes induced during successful sciatic
      nerve regeneration. The small proline-rich repeat protein 1A (SPRR1A) is not
      detectable in uninjured neurons but is induced by >60-fold after peripheral
      axonal damage. The protein is localized to injured neurons and axons. sprr1a is
      one of a group of epithelial differentiation genes, including s100c and p21/waf,
      that are coinduced in neurons by axotomy. Overexpressed SPRR1A colocalizes with F
      actin in membrane ruffles and augments axonal outgrowth on a range of substrates.
      In axotomized sensory neurons, reduction of SPRR1A function restricts axonal
      outgrowth. Neuronal SPRR1A may be a significant contributor to successful nerve
      regeneration.

PMID- 11850459
TI  - Brain-derived neurotrophic factor modulates cerebellar plasticity and synaptic
      ultrastructure.
AB  - Neurotrophins are key regulators of neuronal survival and function. Here we show
      that TrkB, the receptor for brain-derived neurotrophic factor (BDNF), is located
      at parallel fiber to Purkinje cell (PF/PC) synapses of the cerebellum. To
      determine the effects of TrkB receptor activation on synapse formation and
      function, we examined the parallel fiber to Purkinje cell synapses of mice with a
      targeted deletion of the BDNF gene. Although Purkinje cell dendrites are abnormal
      in BDNF -/- mice, PF/PC synapses are still able to form. Immunohistochemical
      analysis of mutant animals revealed the formation of numerous PF/PC synapses with
      the appropriate apposition of presynaptic and postsynaptic proteins. These
      synapses are functional, and no differences were detected in the waveform of
      evoked EPSCs, the amplitude of spontaneous mini-EPSCs, or the response to
      prolonged 10 Hz stimulus trains. However, paired-pulse facilitation, a form of
      short-term plasticity, is significantly decreased in BDNF -/- mice. Detailed
      ultrastructural analysis of the presynaptic terminals demonstrated that this
      change in synaptic function is accompanied by an increase in the total number of
      synaptic vesicles in mutant mice and a decrease in the proportion of vesicles
      that are docked. These data suggest that BDNF regulates both the mechanisms that
      underlie short-term synaptic plasticity and the steady-state relationship between
      different vesicle pools within the terminal.

PMID- 11850460
TI  - Activity deprivation reduces miniature IPSC amplitude by decreasing the number of
      postsynaptic GABA(A) receptors clustered at neocortical synapses.
AB  - Maintaining the proper balance between excitation and inhibition is necessary to
      prevent cortical circuits from either falling silent or generating epileptiform
      activity. One mechanism through which cortical networks maintain this balance is
      through the activity-dependent regulation of inhibition, but whether this is
      achieved primarily through changes in synapse number or synaptic strength is not
      clear. Previously, we found that 2 d of activity deprivation increased the
      amplitude of miniature EPSCs (mEPSCs) onto cultured visual cortical pyramidal
      neurons. Here we find that this same manipulation decreases the amplitude of
      mIPSCs. This occurs with no change in single-channel conductance but is
      accompanied by a reduction in the average number of channels open during the
      mIPSC peak and a reduction in the intensity of staining for GABA(A) receptors
      (GABA(A)Rs) at postsynaptic sites. In addition, the number of synaptic sites that
      express detectable levels of GABA(A)Rs was decreased by approximately 50% after
      activity blockade, although there was no reduction in the total number of
      presynaptic contacts. These data suggest that activity deprivation reduces
      cortical inhibition by reducing both the number of GABA(A)Rs clustered at
      synaptic sites and the number of functional inhibitory synapses. Because
      excitatory and inhibitory synaptic currents are regulated in opposite directions
      by activity blockade, these data suggest that the balance between excitation and
      inhibition is dynamically regulated by ongoing activity.

PMID- 11850461
TI  - Eph receptor tyrosine kinase-mediated formation of a topographic map in the
      Drosophila visual system.
AB  - Roles for Eph receptor tyrosine kinase signaling in the formation of topographic
      patterns of axonal connectivity have been well established in vertebrate visual
      systems. Here we describe a role for a Drosophila Eph receptor tyrosine kinase
      (EPH) in the control of photoreceptor axon and cortical axon topography in the
      developing visual system. Although uniform across the developing eye, EPH is
      expressed in a concentration gradient appropriate for conveying positional
      information during cortical axon guidance in the second-order optic ganglion, the
      medulla. Disruption of this graded pattern of EPH activity by double-stranded RNA
      interference or by ectopic expression of wild-type or dominant-negative
      transgenes perturbed the establishment of medulla cortical axon topography. In
      addition, abnormal midline fasciculation of photoreceptor axons resulted from the
      eye-specific expression of the dominant-negative EPH transgene. These
      observations reveal a conserved role for Eph kinases as determinants of
      topographic map formation in vertebrates and invertebrates.

PMID- 11850462
TI  - Ionic mechanism of ouabain-induced concurrent apoptosis and necrosis in
      individual cultured cortical neurons.
AB  - Energy deficiency and dysfunction of the Na+, K+-ATPase are common consequences
      of many pathological insults. The nature and mechanism of cell injury induced by
      impaired Na+, K+-ATPase, however, are not well defined. We used cultured cortical
      neurons to examine the hypothesis that blocking the Na+, K+-ATPase induces
      apoptosis by depleting cellular K+ and, concurrently, induces necrotic injury in
      the same cells by increasing intracellular Ca2+ and Na+. The Na+, K+-ATPase
      inhibitor ouabain induced concentration-dependent neuronal death. Ouabain
      triggered transient neuronal cell swelling followed by cell shrinkage,
      accompanied by intracellular Ca2+ and Na+ increase, K+ decrease, cytochrome c
      release, caspase-3 activation, and DNA laddering. Electron microscopy revealed
      the coexistence of ultrastructural features of both apoptosis and necrosis in
      individual cells. The caspase inhibitor Z-Val-Ala-Asp(OMe)-fluoromethyl ketone (Z
      VAD-FMK) blocked >50% of ouabain-induced neuronal death. Potassium channel
      blockers or high K+ medium, but not Ca2+ channel blockade, prevented cytochrome c
      release, caspase activation, and DNA damage. Blocking of K+, Ca2+, or Na+
      channels or high K+ medium each attenuated the ouabain-induced cell death;
      combined inhibition of K+ channels and Ca2+ or Na+ channels resulted in
      additional protection. Moreover, coapplication of Z-VAD-FMK and nifedipine
      produced virtually complete neuroprotection. These results suggest that the
      neuronal death associated with Na+, K+-pump failure consists of concurrent
      apoptotic and necrotic components, mediated by intracellular depletion of K+ and
      accumulation of Ca2+ and Na+, respectively. The ouabain-induced hybrid death may
      represent a distinct form of cell death related to the brain injury of inadequate
      energy supply and disrupted ion homeostasis.

PMID- 11850463
TI  - A role of the ubiquitin-proteasome system in neuropathic pain.
AB  - Neuropathic pain (characterized by hyperalgesia and allodynia to mechanical and
      thermal stimuli) causes cellular changes in spinal dorsal horn neurons, some of
      which parallel those in synaptic plasticity associated with learning. Ubiquitin C
      terminal hydrolase (UCH) appears to play a key role in long-term facilitation in
      Aplysia. The cooperation of UCH with the proteolytic enzyme complex known as the
      proteasome is required for the degradation of a number of signaling molecules
      within the cell that may remove normal restraints on synaptic plasticity. We have
      used electrophysiology, in situ hybridization histochemistry, semiquantitative RT
      PCR, Western blotting, and in vivo behavioral reflex analysis to investigate the
      ubiquitin-proteasome system in a model of neuropathic pain. In neuropathic
      animals, ionophoretic application of selective proteasome inhibitors attenuated
      dorsal horn neuron firing evoked by normally innocuous brush or cold stimuli and
      by noxious mustard oil stimuli. In control animals, only mustard oil-evoked
      responses were inhibited. Intrathecal administration of proteasome inhibitors
      attenuated hyperalgesia and allodynia in neuropathic rats. Expression of UCH-L1
      (a rat homolog of Aplysia neuronal UCH and of the human UCH-L1, also known as PGP
      9.5) and its mRNA were selectively increased within the ipsilateral dorsal horn
      of neuropathic rats, supporting the idea of a role for the ubiquitin-proteasome
      system in nociceptive processing. Proteasome inhibitors selectively attenuate
      allodynic and hyperalgesic responses in neuropathic pain, with some reduction in
      normal nociceptive, but not non-nociceptive responses, and potentially represent
      a novel therapeutic strategy for neuropathic pain.

PMID- 11850464
TI  - Hippocampal population activity during the small-amplitude irregular activity
      state in the rat.
AB  - The sleeping rat cycles between two well-characterized physiological states, slow
      wave sleep (SWS) and rapid-eye-movement sleep (REM), often identified by the
      presence of large-amplitude irregular activity (LIA) and theta activity,
      respectively, in the hippocampal EEG. Inspection of the activity of ensembles of
      hippocampal CA1 complex-spike cells along with the EEG reveals the presence of a
      third physiological state within SWS. We characterize the hippocampal EEG and
      population activity of this third state relative to theta activity and LIA, its
      incidence relative to REM and LIA, and the functional correlates of its
      population activity. This state occurs repeatedly within stretches of SWS,
      occupying approximately 33% of SWS and approximately 20% of total sleep, and it
      follows nearly every REM episode; however, it never occurs just before a REM
      episode. The EEG during this state becomes low in amplitude for a few seconds,
      probably corresponding to "small-amplitude irregular activity" (SIA) described in
      the literature; we will call its manifestation during sleep "S-SIA." During S
      SIA, a small subset of cells becomes active, whereas the rest remain nearly
      silent, with the same subset of cells active across long sequences of S-SIA
      episodes. These cells are physiologically indistinguishable from ordinary complex
      spike cells; thus, the question arises as to whether they have any special
      functional correlates. Indeed, many of these cells are found to have place fields
      encompassing the location where the rat sleeps, raising the possibility that S
      SIA is a state of increased alertness in which the animal's location in the
      environment is represented in the brain.

PMID- 11850465
TI  - Opposite actions of brain-derived neurotrophic factor and neurotrophin-3 on
      firing features and ion channel composition of murine spiral ganglion neurons.
AB  - It is now well established that sensory neurons and receptors display
      characteristic morphological and electrophysiological properties tailored to
      their functions. This is especially evident in the auditory system, where cells
      are arranged tonotopically and are highly specialized for precise coding of
      frequency- and timing-dependent auditory information. Less well understood,
      however, are the mechanisms that give rise to these biophysical properties. We
      have provided insight into this issue by using whole-cell current-clamp
      recordings and immunocytochemistry to show that BDNF and NT-3, neurotrophins
      found normally in the cochlea, have profound effects on the firing properties and
      ion channel distribution of spiral ganglion neurons in the murine cochlea.
      Exposure of neurons to BDNF caused all neurons, regardless of their original
      cochlear position, to display characteristics of the basal neurons. Conversely,
      NT-3 caused cells to show the properties of apical neurons. These results are
      consistent with oppositely oriented gradients of these two neurotrophins and/or
      their high-affinity receptors along the tonotopic map, and they suggest that a
      combination of neurotrophins are necessary to establish the characteristic firing
      features of postnatal spiral ganglion neurons.

PMID- 11850466
TI  - Dynamic cortical and subcortical networks in learning and delayed recall of timed
      motor sequences.
AB  - We used positron emission tomography to examine learning and retention of timed
      motor sequences. Subjects were scanned during learning (LRN) and baseline (ISO)
      on 3 d: day 1, after 5 d of practice (day 5) and after a 4 week delay (recall).
      Blood flow was compared across days of learning and between the LRN and ISO
      conditions. Overall, significant changes in activity were seen across days for
      the LRN condition, but not the ISO baseline. Day 1 results revealed extensive
      activation in the cerebellar cortex, particularly lobules III/IV and VI. Day 5
      results showed increased activity in the basal ganglia (BG) and frontal lobe,
      with no significant cerebellar activity. At recall, significantly greater
      activity was seen in M1, premotor, and parietal cortex. Blood flow in the
      cerebellum decreased significantly between day 1 and recall. These results reveal
      a dynamic network of motor structures that are differentially active during
      different phases of learning and delayed recall. For the first time our findings
      show that recall of motor sequences in humans is mediated by a predominantly
      cortical network. Based on these results, we suggest that during early learning
      cerebellar mechanisms are involved in adjusting movement kinematics according to
      sensory input to produce accurate motor output. Thereafter, the cerebellar
      mechanisms required for early learning are no longer called into play. During
      late learning, the BG may be involved in automatization. At delayed recall,
      movement parameters appear to be encoded in a distributed representation mediated
      by M1, premotor, and parietal cortex.

PMID- 11850467
TI  - Distinct roles for nigral GABA and glutamate receptors in the regulation of
      dendritic dopamine release under normal conditions and in response to systemic
      haloperidol.
AB  - The regulation of dendritic dopamine release in the substantia nigra (SN) likely
      involves multiple mechanisms. GABA and glutamate inputs to nigrostriatal dopamine
      neurons exert powerful influences on dopamine neuron physiology; therefore, it is
      probable that GABA and glutamate likewise influence dendritic dopamine release,
      at least under some conditions. The present studies used in vivo microdialysis to
      determine the potential roles of nigral GABA and glutamate receptors in the
      regulation of dendritic dopamine release under normal conditions and when
      dopamine signaling in the basal ganglia is compromised after systemic haloperidol
      administration. Nigral application of the GABA(A) receptor antagonist bicuculline
      by reverse dialysis significantly increased spontaneous dopamine efflux in the
      SN. However, spontaneous dopamine efflux in the SN was not significantly affected
      by local application of the glutamate receptor antagonists 6-cyano-7
      nitroquinoxaline-2,3-dione or (+/-)-3-[2-carboxypiperazine-4-yl]-propyl-1
      phosphonic acid. Systemic haloperidol administration significantly increased the
      extracellular dopamine measured in the SN. Blockade of nigral GABA(A) receptors
      by local bicuculline application did not alter this effect of systemic
      haloperidol, despite the bicuculline-induced increase in spontaneous dendritic
      dopamine efflux. In contrast, nigral application of either glutamate receptor
      antagonist significantly attenuated the increases in dendritic dopamine efflux
      elicited by systemic haloperidol. These data suggest that under normal
      conditions, activity of GABA afferents to SN dopamine neurons is an important
      determinant of the spontaneous level of dendritic dopamine release. Circuit-level
      changes in the basal ganglia involving an increased glutamatergic drive to the SN
      appear to underlie the increase in dendritic dopamine release that occurs in
      response to systemic haloperidol administration.

PMID- 11850468
TI  - Critical time-window for NO-cGMP-dependent long-term memory formation after one
      trial appetitive conditioning.
AB  - The nitric oxide (NO)-cGMP signaling pathway is implicated in an increasing
      number of experimental models of plasticity. Here, in a behavioral analysis using
      one-trial appetitive associative conditioning, we show that there is an
      obligatory requirement for this pathway in the formation of long-term memory
      (LTM). Moreover, we demonstrate that this requirement lasts for a critical period
      of approximately 5 hr after training. Specifically, we trained intact specimens
      of the snail Lymnaea stagnalis in a single conditioning trial using a conditioned
      stimulus, amyl-acetate, paired with a salient unconditioned stimulus, sucrose,
      for feeding. Long-term associative memory induced by a single associative trial
      was demonstrated at 24 hr and shown to last at least 14 d after training. Tests
      for LTM and its dependence on NO were performed routinely 24 hr after training.
      The critical period when NO was needed for memory formation was established by
      transiently depleting it from the animals at a series of time points after
      training by the injection of the NO-scavenger 2-phenyl-4,4,5,5-tetramethyl
      imidazoline-1-oxyl 3-oxide (PTIO). By blocking the activity of NO synthase and
      soluble guanylyl cyclase enzymes after training, we provided further evidence
      that LTM formation depends on an intact NO-cGMP pathway. An electrophysiological
      correlate of LTM was also blocked by PTIO, showing that the dependence of LTM on
      NO is amenable to analysis at the cellular level in vitro. This represents the
      first demonstration that associative memory formation after single-trial
      appetitive classical conditioning is dependent on an intact NO-cGMP signaling
      pathway.

PMID- 11850469
TI  - Patterns of hand motion during grasping and the influence of sensory guidance.
AB  - This study was aimed at describing temporal synergies of hand movement and
      determining the influence of sensory cues on the control of these synergies.
      Subjects were asked to reach to and grasp various objects under three
      experimental conditions: (1) memory-guided movements, in which the object was not
      in view during the movement; (2) virtual object, in which a virtual image of the
      object was in view but the object was not physically present; and (3) real
      object, in which the object was in view and physically present. Motion of the arm
      and of 15 degrees of freedom of the hand was recorded. A principal components
      analysis was developed to provide a concise description of the spatiotemporal
      patterns underlying the motion. Vision of the object during the reaching movement
      had no influence on the kinematics, and the effect of the physical presence of
      the object became manifest primarily after the fingers had contacted the object.
      Two principal components accounted for >75% of the variance. For both components,
      there was a strong positive correlation in the rotations of metacarpophalangeal
      and proximal interphalangeal joints of the fingers. The first principal component
      exhibited a pattern of finger extension reversing to flexion, whereas the second
      principal component became important only in the second half of the reaching
      movement.

PMID- 11850470
TI  - Chronic treatment with the antidepressant amitriptyline prevents impairments in
      water maze learning in aging rats.
AB  - Increasing evidence links chronically elevated glucocorticoid levels and
      cognitive impairments in a subpopulation of aged rodents and humans.
      Antidepressant drugs improve hypothalamic-pituitary-adrenal axis feedback
      regulation and reduce plasma glucocorticoid levels. Decreasing the cumulative
      lifetime exposure to glucocorticoid excess by long-term exposure to
      antidepressants may prevent the emergence of cognitive impairments in aged rats.
      To test this hypothesis, we treated middle-aged male Lister hooded rats (16
      months) with amitriptyline until they were 24 months of age, and their cognitive
      function was assessed in the water maze. Performance in the spatial learning task
      declined significantly with aging (p < 0.01), with 33% of aged controls showing
      poorer (<2.5 SD) probe test performance than young controls. Amitriptyline
      treatment from midlife preserved water maze performance with aging (p < 0.01
      compared with aged controls) and significantly (p < 0.01) reduced the proportion
      of poor performers (7%). Measures of anxiety-related behaviors in the elevated
      plus-maze were significantly (p < 0.05) decreased in the aged rats after
      amitriptyline. Furthermore, evening plasma corticosterone levels were reduced
      (30% decrease; p < 0.01 compared with aged controls) after 6 months of
      amitriptyline. These data suggest that long-term treatment with amitriptyline
      decreases the prevalence of cognitive impairment in aged rats and that this may,
      in part, be a consequence of reduced plasma corticosterone levels and reduced
      anxiety.

PMID- 11850471
TI  - Blocking GABAergic inhibition increases sensitivity to sound motion cues in the
      inferior colliculus.
AB  - Responses of low-frequency neurons in the inferior colliculus (IC) of
      anesthetized guinea pigs were recorded to interaural phase modulation (IPM)
      before, during, and after iontophoresis of bicuculline, an antagonist to the
      inhibitory neurotransmitter GABA. Sensitivity to the direction of virtual motion
      resulting from IPM is an emergent property of neurons at the level of the IC. One
      model to account for this emergent sensitivity depends on GABAergic inhibition.
      Blocking GABAergic inhibition with bicuculline substantially increased neuronal
      discharge rates and increased the extent to which neurons were sensitive to the
      apparent-motion cues of IPM. The effect of GABA blockade is consistent with the
      hypothesis that sensitivity to the motion cues of IPM results from a process of
      adaptation-of-excitation whereby the magnitude of the recent response history
      influences subsequent neuronal responsiveness. These results indicate that
      GABAergic inhibition strongly influences the context-dependent processing of low
      frequency binaural signals in the IC.

PMID- 11850472
TI  - The coding of spatial location by single units in the lateral superior olive of
      the cat. I. Spatial receptive fields in azimuth.
AB  - The lateral superior olive (LSO) is one of the most peripheral auditory nuclei
      receiving inputs from both ears, and LSO neurons are sensitive to interaural
      level differences (ILDs), one of the primary acoustical cues for sound location.
      We used the virtual space (VS) technique to present over earphones broadband
      stimuli containing natural combinations of localization cues as a function of
      azimuth while recording extracellular responses from single LSO cells. The
      responses of LSO cells exhibited spatial receptive fields (SRFs) in azimuth
      consonant with their sensitivity to ILDs of stimuli presented dichotically: high
      discharge rates for ipsilateral azimuths where stimulus amplitude to the
      excitatory ear exceeded that to the inhibitory ear, rapidly declining rates near
      the midline, and low rates for contralateral azimuths where the amplitude to the
      inhibitory ear exceeded that to the excitatory ear. Relative to binaural
      stimulation, presentations of the VS stimuli to the ipsilateral ear alone yielded
      increased rates, particularly in the contralateral field, confirming that the
      binaural SRFs were shaped by contralateral inhibition. Our finding that LSO
      neurons respond to azimuth consistent with their ILD sensitivity supports the
      long-held hypothesis that LSO neurons compute a correlate of the ILD present in
      free-field stimuli. Only weak correlations between the properties of pure-tone
      ILD functions and the SRFs were found, indicating that ILD sensitivity measured
      at only one sound level is not sufficient to predict sensitivity to azimuth.
      Sensitivity to spatial location was also retained over a wide range of stimulus
      levels under binaural, but not monaural, conditions.

PMID- 11850473
TI  - The coding of spatial location by single units in the lateral superior olive of
      the cat. II. The determinants of spatial receptive fields in azimuth.
AB  - The lateral superior olive (LSO) is one of the most peripheral nuclei in the
      auditory pathway to receive inputs from both ears, and its cells are sensitive to
      interaural level disparities (ILDs) when stimulated by sounds presented over
      earphones. It has, accordingly, long been hypothesized that the functional role
      of the LSO is to encode a correlate of ILDs, one of the acoustical cues to the
      spatial location of sound. In the companion paper, we used the virtual space (VS)
      technique to present over earphones stimuli containing all the acoustical cues to
      the location of broadband stimuli and measured the spatial receptive fields
      (SRFs) in azimuth of single LSO cells. The shapes of the SRFs were generally
      consistent with the ILD sensitivity of the cells (Tollin and Yin, 2002), but
      because the only variable under our control was azimuth, and not ILD directly,
      the precise cues responsible for the SRFs could not be unambiguously determined.
      Here, we test more directly the hypothesis that ILDs are the primary determinants
      of the SRFs in azimuth of LSO cells by digitally manipulating the head-related
      transfer functions used to create the VS stimuli by independently varying (or
      holding constant) in azimuth each of the primary localization cues in isolation
      while holding constant (or varying) the others. Our results support the classical
      view of the LSO that the form of the SRFs of the cells in azimuth is determined
      primarily by the ILDs in a small band of frequencies around the characteristic
      frequencies of the cells.

PMID- 11850474
TI  - Cortical focus drives widespread corticothalamic networks during spontaneous
      absence seizures in rats.
AB  - Absence seizures are the most pure form of generalized epilepsy. They are
      characterized in the electroencephalogram by widespread bilaterally synchronous
      spike-wave discharges (SWDs), which are the reflections of highly synchronized
      oscillations in thalamocortical networks. To reveal network mechanisms
      responsible for the initiation and generalization of the discharges, we studied
      the interrelationships between multisite cortical and thalamic field potentials
      recorded during spontaneous SWDs in the freely moving WAG/Rij rat, a genetic
      model of absence epilepsy. Nonlinear association analysis revealed a consistent
      cortical "focus" within the peri-oral region of the somatosensory cortex. The
      SWDs recorded at other cortical sites consistently lagged this focal site, with
      time delays that increased with electrode distance (corresponding to a mean
      propagation velocity of 1.4 m/sec). Intra-thalamic relationships were more
      complex and could not account for the observed cortical propagation pattern.
      Cortical and thalamic sites interacted bi-directionally, whereas the direction of
      this coupling could vary throughout one seizure. However, during the first 500
      msec, the cortical focus was consistently found to lead the thalamus. These
      findings argue against the existence of one common subcortical pacemaker for the
      generation of generalized spike-wave discharges characteristic for absence
      seizures in the rat. Instead, the results suggest that a cortical focus is the
      dominant factor in initiating the paroxysmal oscillation within the
      corticothalamic loops, and that the large-scale synchronization is mediated by
      ways of an extremely fast intracortical spread of seizure activity. Analogous
      mechanisms may underlie the pathophysiology of human absence epilepsy.

PMID- 11850475
TI  - Incremental value of left ventricular ejection fraction for detection of
      multivessel coronary artery disease in exercise (201)Tl gated myocardial
      perfusion imaging.
AB  - Assessment of reversible defects in exercise (201)Tl perfusion SPECT has low
      sensitivity and high specificity for detection of multivessel coronary artery
      disease (CAD). The goal of this study was to evaluate whether the left
      ventricular ejection fraction (LVEF) in exercise (201)Tl gated SPECT had
      incremental diagnostic value over perfusion data for detection of multivessel
      CAD. METHODS: One hundred eighty-two patients underwent exercise (201)Tl gated
      SPECT. Automated LV function analysis software was used for calculation of the
      postexercise and the rest LVEF. The best threshold between 0- to 1-vessel CAD and
      2- to 3-vessel CAD was determined as the cutoff that on receiver-operating
      characteristic analysis resulted in the best sensitivity for detection of
      multivessel CAD with an associated specificity of >90%. RESULTS: Only 18 (26.9%)
      of 67 patients with multivessel CAD had reversible defects in multiple
      territories. Sensitivities of the postexercise and the rest LVEF and the
      worsening of the LVEF by exercise did not differ from those of perfusion data
      alone. Sensitivities of the combination of perfusion data and the postexercise
      and rest LVEF did not differ from those of perfusion data alone, whereas the
      sensitivity of the combination of perfusion data and worsening of the LVEF (i.e.,
      reversible defects in multiple territories or worsening of the LVEF >5.6% [or
      both]) was significantly greater than that of perfusion data alone (43.3% vs.
      26.9%; P < 0.05), with an acceptable level of specificity (90.4%). CONCLUSION:
      The worsening of the LVEF by exercise has the potential to detect patients with
      multivessel CAD among those without multivessel patterns of reversible defects.

PMID- 11850476
TI  - Diagnostic value of (111)In-granulocyte scintigraphy in patients with fever of
      unknown origin.
AB  - 111In-granulocyte scintigraphy is often used as a diagnostic tool in patients
      with fever of unknown origin (FUO). However, its diagnostic performance has been
      studied in only a limited number of investigations, with most having been
      published more than 10 y ago; in addition, a broad range of sensitivities and
      specificities has been reported. Therefore, the aim of this study was to
      investigate the diagnostic value of granulocyte scintigraphy in patients
      fulfilling the criteria of FUO. Also studied was whether increased peripheral
      leukocyte count or C-reactive protein (CRP) level could be used to select
      patients for scintigraphy to raise the diagnostic value. METHODS: For 31 patients
      with true FUO who underwent granulocyte scintigraphy at a third-line referral
      hospital between 1995 and 2000, the files and scintigraphy findings were reviewed
      retrospectively to test the ability of scintigraphy to identify infection or
      chronic inflammatory bowel disease as the cause of FUO. In addition, leukocyte
      counts and CRP values were recorded. RESULTS: Scintigrams were true-positive in 6
      cases, false-positive in 4 cases, true-negative in 19 cases, and false-negative
      in 2 cases. Sensitivity was 75%, specificity was 83%, the predictive value of a
      scintigram showing positive findings was 60%, and the predictive value of a
      scintigram showing negative findings was 90%. Leukocyte counts did not differ
      between patients with true-positive and true-negative scintigrams. In contrast,
      CRP was elevated in all patients with true-positive scintigrams but in only half
      the patients with true-negative scintigrams. However, if only patients with
      elevated CRP were used for calculation of test performance, the test performance
      was not improved. CONCLUSION: (111)In-granulocyte scintigraphy seems to have a
      reasonable sensitivity and specificity in cases of FUO, when one takes into
      account that (111)In-granulocyte scintigraphy is not a first-line test. The high
      predictive value of a scintigram showing negative findings may be especially
      valuable for ruling out an infectious cause of FUO. Neither peripheral leukocyte
      count nor CRP levels seem useful for selection of patients on whom scintigraphy
      should be performed.

PMID- 11850477
TI  - Uptake of (201)Tl into primary cell cultures from human thyroid tissue is
      multiplied by TSH.
AB  - According to current guidelines, (201)Tl scintigraphy aiming at the detection of
      iodine-negative metastases of differentiated thyroid carcinoma is usually
      performed during hormone replacement in thyroid-stimulating hormone (TSH)
      suppressive doses. The aim of this study was to determine the effect of TSH on
      thyroid (201)Tl uptake in vitro. METHODS: Adherent monolayers of human thyroid
      tissue (1.965-3.000 million cells) were cultured after mechanical disintegration
      and enzymatic digestion by neutral protease. The samples were derived from
      patients undergoing surgical treatment of nodular goiter. Studies were performed
      on paranodular tissue components, exclusively. Cells originating from identical
      tissue samples were dispensed into matched-pair cultures and incubated in
      parallel by a TSH-free medium and by a medium containing 10 IU/L bovine TSH.
      Thyroglobulin (Tg) accumulation was calculated after repetitive measurements of
      Tg concentrations by radioimmunoassay. Uptake studies were initiated by adding
      fresh medium containing (201)Tl (8.2-91.0 kBq). After 1 h of incubation, the
      media were removed and the cells were detached by trypsin and collected by
      centrifugation. Uptake was measured by a gamma-counter, and cellular uptake
      values were calculated as percentages of total activity normalized to 1 million
      cells. The statistical significance of differences in Tg release and (201)Tl
      uptake was corroborated in a generalized estimating equations analysis taking the
      variability of unbalanced replicate measurements into account. RESULTS: Cells
      cultured in the presence of TSH displayed a 2-fold release of Tg (12.949
      ng/h/million cells vs. 6.049 ng/h/million cells, P = 0.001) and triplicate
      (201)Tl uptake (0.718%/million cells vs. 0.249%/million cells, P = 0.0002).
      CONCLUSION: (201)Tl uptake in human thyroid cells is significantly increased by
      TSH. These data suggest that withdrawal of thyroid hormone substitution has the
      potential to improve the sensitivity of (201)Tl scintigraphy for detecting
      thyroid remnants or cancer recurrences. This suggestion should be further
      investigated in patients and in cell cultures from thyroid carcinomas.

PMID- 11850479
TI  - Influence of implementation parameters on registration of MR and SPECT brain
      images by maximization of mutual information.
AB  - Mutual-information maximization is one of the most popular algorithms for
      automatic image registration. However, many implementation issues have not been
      evaluated in a single, coherent context. METHODS: Twenty-one registrations
      between MR and SPECT brain images (8 patients) were achieved by mutual
      information maximization with different implementation strategies. The results of
      a popular strategy were chosen as the standard. All other results were compared
      with the standard, and the statistics of misregistrations were computed. The
      registration speed, accuracy, precision, and success rate were assessed. RESULTS:
      Compared with trilinear interpolation, nearest-neighbor interpolation slightly
      sped the registration process, but with a lower success rate. The number of bins
      used to estimate the probability density function (pdf) affects the speed and
      robustness. Using fewer bins yielded a less robust registration. Adaptively
      changing the number of bins increased the registration speed and robustness.
      Simplex optimization increased the registration speed considerably, with a
      slightly degraded success rate. Simplex optimization with adaptive bin strategy
      improved the success rate and further decreased the registration time.
      Multiresolution optimization yielded a better success rate, with little effect on
      the accuracy and precision of registration. An increase in the number of
      resolution levels increased the success rate. Multisampling optimization also
      improved the success rate, but the results were less accurate and precise than
      those obtained with multiresolution optimization, with an increase in the number
      of levels decreasing the performance. Segmentation affected the registration
      speed and success rate. Because segmentation is problem specific, the effects
      were not conclusive. CONCLUSION: Different implementation strategies considerably
      affect the performance of automatic image registration by mutual-information
      maximization. On the basis of the experimental findings, we suggest that the best
      implementation strategy would include trilinear interpolation, adaptive change of
      the number of bins when estimating pdf, and exploitation of a simplex
      optimization algorithm with a multiresolution scheme.

PMID- 11850478
TI  - Dopamine transporter concentration is reduced in asymptomatic Machado-Joseph
      disease gene carriers.
AB  - Dopamine transporter (DAT) binding is decreased in Machado-Joseph disease (MJD)
      patients. To further investigate the DAT activity in asymptomatic MJD (aMJD) gene
      carriers, we performed this prospective study using (99m)Tc-TRODAT-1
      ([(99m)Tc][2[[2-[[[3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3,2,1]oct-2-yl]
      methyl](2-mercaptoethyl)amino]ethyl]amino]ethane-thiolato(3-)-N2,N2',S2,S2]oxo
      [1R-(exo-exo)])) brain SPECT on 5 aMJD gene carriers, 10 age-matched MJD
      patients, and 10 age-matched healthy control subjects. METHODS: Brain SPECT
      images were acquired 4 h after intravenous injection of 925 MBq (25 mCi) (99m)Tc
      T RODAT-1, which is known to bind specifically to the DAT on the nigrostriatal
      terminals. By fusing these SPECT images with a striatal atlas, obtained from MRI,
      binding of this tracer in the entire striatum was measured and the uptake values
      in bilateral striatal areas were compared between these 3 groups. RESULTS: The
      uptake values of the aMJD gene carriers (P < 0.001) and MJD patients (P < 0.001)
      displayed a significant reduction compared with those of the control subjects.
      The reduction was more severe in the MJD patient group (P < 0.05). Bilateral
      putamen-to-caudate ratios were significantly lower in the aMJD gene carrier and
      MJD patient groups (P < 0.001). The dopamine neuronal activity, as represented by
      the tracer binding, was more prominently affected in the putamen in these
      patients and gene carriers. CONCLUSION: (99m)Tc-TRODAT-1 brain SPECT is capable
      of detecting early alteration of dopamine neurons in the striatal region.
      Significantly, the results suggest that this impairment of presynaptic dopamine
      function actually occurs at an early stage, which was previously unrecognized in
      these aMJD gene carriers.

PMID- 11850480
TI  - Comparison of (11)C-choline and (18)F-FDG PET in primary diagnosis and staging of
      patients with thoracic cancer.
AB  - PET with (18)F-FDG is used for detection and staging of thoracic cancer; however,
      more specific PET radiopharmaceuticals would be welcome. (11)C-labeled choline
      (CHOL) is a new radiopharmaceutical potentially useful for tumor imaging, since
      it is incorporated into cell membranes as phosphatidylcholine. The aim of this
      study was to investigate whether (11)C-CHOL PET has advantages over (18)F-FDG PET
      in patients with thoracic cancer. METHODS: We evaluated 17 patients with thoracic
      cancer both with (11)C-CHOL PET and (18)F-FDG PET. After transmission scanning,
      (11)C-CHOL was injected intravenously, and whole-body scanning was started after
      5 min. Immediately thereafter, (18)F-FDG was injected intravenously, followed
      after 90 min by interleaved attenuation-corrected whole-body scanning. Scans were
      performed from crown to femur. Visual and quantitative (standardized uptake
      value) analyses of (11)C-CHOL PET and (18)F-FDG PET were performed and compared
      with results of traditional staging and follow-up. RESULTS: The most prominent
      features of normal (11)C-CHOL distribution were high uptake in liver, renal
      cortex, and salivary glands. Except for some uptake in choroid plexus and
      pituitary gland, brain uptake was negligible. All primary thoracic tumors were
      detected with (11)C-CHOL PET and (18)F-FDG PET. Both (11)C-CHOL PET and (18)F-FDG
      PET correctly identified all 16 patients with lymph node involvement. However, in
      a lesion-to-lesion analysis, (11)C-CHOL PET detected only 29 of 43 metastatic
      lymph nodes, whereas (18)F-FDG PET detected 41 of 43. (11)C-CHOL PET detected
      fewer intrapulmonary and pleural metastases than (18)F-FDG PET (27/47 vs. 46/47).
      More brain metastases were detected with (11)C-CHOL PET (23/23) than with (18)F
      FDG PET (3/23). For primary tumors, the median (range) standard uptake values of
      (11)C-CHOL and (18)F-FDG were 1.68 (0.98-3.22) and 4.22 (1.40-8.26), respectively
      (P = 0.001). CONCLUSION: (11)C-CHOL PET can be used to visualize thoracic
      cancers. Although detection of lymph node metastases with (11)C-CHOL PET was
      inferior compared with (18)F-FDG PET, the detection of brain metastases was
      superior.

PMID- 11850481
TI  - Relationship between retention index in dual-phase (18)F-FDG PET, and hexokinase
      II and glucose transporter-1 expression in pancreatic cancer.
AB  - Recently, some studies have shown that delayed scanning with (18)F-FDG PET may
      help to differentiate malignant from benign pancreatic lesions. However, no study
      has evaluated the relationship between temporal changes in (18)F-FDG uptake and
      expression of hexokinase or glucose transporter. METHODS: Twenty-one consecutive
      patients with pancreatic cancer were studied preoperatively by dual-phase (18)F
      FDG PET, performed 1 and 2 h after injection of (18)F-FDG. The standardized
      uptake value (SUV) of the pancreatic cancer was determined, and the retention
      index (RI) (%) was calculated by subtracting the SUV at 1 h (SUV1) from the SUV
      at 2 h (SUV2) and dividing by SUV1. The percentages of cells strongly expressing
      hexokinase type-II (HK-II) and glucose transporter-1 (GLUT-1) were scored on a 5
      point scale (1 = 0%-20%, 2 = 20%-40%, 3 = 40%-60%, 4 = 60%-80%, 5 = 80%-100%) by
      visual analysis of immunohistochemical staining of paraffin sections from the
      tumor specimens using anti-HK-II and anti-GLUT-1 antibody (HK-index and G-index,
      respectively). RESULTS: SUV2 (mean +/- SD, 5.7 +/- 2.6) was higher than SUV1 (5.1
      +/- 2.1), with an RI of 8.5 +/- 11.0. Four cases of cancer, in which SUV2 showed
      a decline from SUV1, showed a low HK-index (1.8 +/- 1.1), whereas 4 cases with an
      RI of > or =20 and 13 cases with an intermediate RI (0-20) showed significantly
      higher HK-indices (4.3 +/- 0.7 and 3.1 +/- 1.5, respectively; P < 0.05). RI
      showed a positive correlation with HK-index, with an R(2) of 0.27 (P < 0.05), but
      no significant correlation with the G-index. SUV1 showed no relationship with the
      HK-index but showed a weak positive correlation with the G-index, with an R(2) of
      0.05 (P = 0.055). CONCLUSION: These preliminary findings suggest that the RI
      obtained from dual-phase (18)F-FDG PET can predict HK-II expression and that the
      SUV (at 1 h) has a positive correlation with GLUT-1 expression but not with HK-II
      expression.

PMID- 11850482
TI  - 11C-acetate PET imaging of prostate cancer.
AB  - 11C-Acetate can act as a probe of tissue metabolism through entry into catabolic
      or anabolic metabolic pathways as mediated by acetyl-coenzyme A. The uptake of
      (11)C-acetate in prostate cancer was investigated to determine whether this
      tracer has potential in tumor identification. METHODS: Twenty-two patients with
      prostate cancer underwent PET after intravenous administration of 740 MBq (11)C
      acetate. Eighteen of the 22 patients were also investigated with (18)F-FDG PET.
      Standardized uptake values (SUVs) for each tumor were investigated for tracer
      activity at 10-20 min after (11)C-acetate and 40-60 min after (18)F-FDG
      administration. RESULTS: Adenocarcinoma of the prostate showed variable uptake of
      (11)C-acetate, with SUVs ranging from 3.27 to 9.87. In contrast, SUVs for (18)F
      FDG ranged from 1.97 to 6.34. By visual inspection, (11)C-acetate accumulation in
      primary prostate tumors was positive in all patients, whereas (18)F-FDG
      accumulation was positive in only 15 of 18 patients. (11)C-Acetate PET in a
      patient with lymph node metastasis showed high intrapelvic accumulation
      corresponding to metastatic sites. Similarly, 2 patients with bone metastases
      were (11)C-acetate avid. CONCLUSION: (11)C-Acetate shows marked uptake in
      prostate cancer and is more sensitive in detection of prostate cancer than is
      (18)F-FDG PET. (11)C-Acetate represents a new tracer for detection of prostate
      cancer with PET, measuring radiopharmaceutical uptake pathways that are different
      from those measured by (18)F-FDG.

PMID- 11850483
TI  - Development of (18)F-fluoroethylcholine for cancer imaging with PET: synthesis,
      biochemistry, and prostate cancer imaging.
AB  - The effectiveness of (11)C-choline PET in detecting various cancers, including
      prostate cancer, is well established. This study was aimed at developing an (18)F
      substituted choline analog, (18)F-fluoroethylcholine (FECh), as a tracer of
      cancer detection. METHODS: No-carrier-added (18)F-FECh was synthesized by 2-step
      reactions: First, tetrabutylammonium (TBA) (18)F-fluoride was reacted with 1,2
      bis(tosyloxy)ethane to yield 2-(18)F-fluoroethyl tosylate; and second, 2-(18)F
      fluoroethyl tosylate was reacted with N,N-dimethylethanolamine to yield (18)F
      FECh, which was then purified by chromatography. An automated apparatus was
      constructed for preparation of the (18)F-FECh injection solution. In vitro
      experiments were performed to examine the uptake of (18)F-FECh in Ehrlich ascites
      tumor cells, and the metabolites were analyzed by solvent extraction followed by
      various kinds of chromatography. Clinical studies of (18)F-FECh PET were
      performed on patients with untreated primary prostate cancer as follows: A
      dynamic (18)F-FECh PET study was performed on 1 patient and static PET studies
      were performed on 16 patients, and the data were compared with those of (11)C
      choline PET on the same patients. RESULTS: (18)F-FECh was prepared in high yield
      and purity. The performance of the automated apparatus was excellent. The in
      vitro experiment revealed that (18)F-FECh was incorporated into tumor cells by
      active transport, then phosphorylated (yielding phosphoryl-(18)F-FECh) in the
      cells, and finally integrated into phospholipids. The clinical PET studies showed
      marked uptake of (18)F-FECh in prostate cancer. A dynamic PET study on 1 patient
      revealed that the blood level of (18)F-FECh decreased rapidly (in 1 min), the
      prostate cancer level became almost maximal in a short period (1.5 min) and it
      remained constant for a long time (60 min), and the urinary radioactivity became
      prominent after a short time lag (5 min). Static PET studies conducted under
      bladder irrigation showed no difference between (18)F-FECh uptake and (11)C
      choline uptake in prostate cancer. However, (18)F-FECh gave a slightly higher
      spatial resolution of the image, which was attributed to the shorter positron
      range of (18)F. CONCLUSION: The synthesis of (18)F-FECh was easy and reliable.
      (18)F-FECh PET was very effective in detecting prostate cancer in patients. The
      chemical trap, consisting of active transport of (18)F-FECh and formation of
      phosphoryl-(18)F-FECh, seemed to be involved in the uptake mechanism of (18)F
      FECh in tumors.

PMID- 11850484
TI  - PET for prostate cancer imaging: still a quandary or the ultimate solution?

PMID- 11850485
TI  - Labeling of mixed leukocytes with (99m)Tc-HMPAO causes severe chromosomal
      aberrations in lymphocytes.
AB  - 99mTc-d,1-hexamethylpropyleneamine oxime (HMPAO) is widely used as a labeling
      agent for leukocytes in the diagnosis of inflammatory or infectious foci.
      Cytotoxicity studies have indicated that intracellular labeling of leukocytes
      with (111)In compounds may have severe detrimental effects on the cells. METHODS:
      In this study, the radiotoxic effects on mixed lymphocytes after labeling with
      (99m)Tc-HMPAO was investigated using the cytokinesis-blocked micronucleus assay
      and chromosomal aberration assay. RESULTS: Whereas negligible numbers of
      chromosome abnormalities were noted in unlabeled lymphocytes, the labeled
      lymphocytes showed multiple aberrations of various types, including dicentric,
      tricentric, and fivecentric chromosomes; centric rings; chromosome and chromatid
      type breaks; and acentric fragments. CONCLUSION: Heavily aberrant lymphocytes are
      seen in (99m)Tc-HMPAO-labeled mixed leukocytes after routine clinical procedures.
      It is unlikely, however, that this would cause detrimental effects, such as
      lymphoid malignancy, as these cells would normally be eliminated through
      apoptosis or phagocytosis.

PMID- 11850486
TI  - False-positive findings on (131)I whole-body scans because of posttraumatic
      superficial scabs.
AB  - Nonspecific (131)I uptake may affect both the specificity and the accuracy of
      whole-body scanning (WBS) performed after (131)I administration in the follow-up
      of thyroid carcinoma after thyroidectomy. We report a newly identified cause of
      false-positive WBS findings: posttraumatic superficial scabs. METHODS: Four
      patients who underwent thyroidectomy for differentiated thyroid carcinoma were
      studied after therapeutic administration of 3,700 MBq (131)I. RESULTS: WBS
      revealed an area of uptake in the lower limbs, in a site corresponding to a
      slight abrasion of the skin that had incidentally occurred between a few hours
      before and 24 h after radioiodine administration. In 2 patients, a radioiodine
      concentration in the scab was shown by the disappearance of the radioactivity in
      the leg after removal of the scab and by detection of radioactivity in the
      collected material. CONCLUSION: Posttraumatic superficial scabs may be a cause of
      false-positive WBS findings. High (131)I doses, although providing increased
      sensitivity, may also increase the number of false-positive results.

PMID- 11850487
TI  - MIRD dose estimate report no. 19: radiation absorbed dose estimates from (18)F
      FDG.

PMID- 11850488
TI  - In vivo quantification and parametric images of the cardiac beta-adrenergic
      receptor density.
AB  - Previous studies showed that the in vivo concentration of beta-adrenergic
      receptor sites can be estimated by PET using (-)-4-((S)-3-tert-butylamino-2
      hydroxypropoxy)-1,3-dihydrobenzoimidazol-2-one (CGP 12177), a hydrophilic ligand.
      A graphic method was previously proposed and used by several groups. However,
      this approach was not completely validated. The purpose of this study was to
      improve and confirm the validity of this approach through a better knowledge of
      the associated ligand-receptor model, estimated for the first time using the
      multiinjection approach. METHODS: The concentration of beta-adrenergic receptor
      sites was estimated for mini pigs using 2 methods. The first was the usual
      multiinjection approach, which permits estimation of all model parameters,
      including receptor concentration. However, this approach needs a complex
      protocol, including blood sampling, thereby making it difficult to use for
      studies on patients. The second method was the CGP 12177 graphic method. This
      approach permits the estimation of only receptor concentration but has the
      advantage of not requiring blood sampling. Another advantage is the ability to
      generate parametric images easily. RESULTS: Using the multiinjection approach, we
      obtained for the first time a complete model describing interactions between CGP
      12177 and beta-adrenergic receptors. Knowledge of all parameters of this model
      permitted good validation of the assumptions included in the graphic method. The
      concentration of beta-adrenergic receptor sites in mini pigs was estimated at
      15.2 +/- 3.4 pmol/mL. CONCLUSION: The graphic method has been improved by taking
      into account various phenomena, such as protein binding and the nonlinearity
      between plasma concentration and injected dose. This method is now usable for
      patient studies and offers the ability to estimate the beta-adrenergic receptor
      concentration from a single PET experiment without blood sampling. Parametric
      imaging will enable screening of the receptor site location and observation of
      potential anomalies in patients.

PMID- 11850489
TI  - SIC, an intracerebral beta(+)-range-sensitive probe for radiopharmacology
      investigations in small laboratory animals: binding studies with (11)C
      raclopride.
AB  - Our aim was to show the ability of a recently developed beta(+)-range-sensitive
      intracerebral probe (SIC) to measure, in vivo, the binding of radioligands in
      small animals. METHODS: The potential of the device for pharmacokinetic studies
      was evaluated by measurement of the dynamic striatal binding of (11)C-raclopride,
      a well-documented D(2) dopaminergic receptor ligand, in rat brain after
      intravenous injection of the labeled compound. The effects of preinjection of the
      unlabeled ligand (raclopride, 2 mg/kg intravenously) and of increasing the
      synaptic dopamine level (amphetamine treatment, 1 mg/kg intravenously) or of
      depleting synaptic dopamine (reserpine pretreatment, 5 mg/kg intraperitoneally)
      on in vivo (11)C-raclopride binding were monitored by SIC. RESULTS: The
      radioactivity curves measured as a function of time were reproducible and
      consistent with previous studies using PET imaging (ratio of striatum to
      cerebellum, 2.6 +/- 0.3 after 20 min). Further studies showed significant
      displacement of (11)C-raclopride by its stable analog. Finally, the device proved
      its capacity to accurately detect changes in (11)C-raclopride binding after a
      sudden (amphetamine) or a gradual (reserpine) modulation of endogenous dopamine
      levels. CONCLUSION: These results show that the new device can monitor binding of
      PET ligands in anesthetized rodents in vivo, with high temporal resolution.

PMID- 11850490
TI  - Preferential accumulation of (3)H-tetraphenylphosphonium in non-small cell lung
      carcinoma in mice: comparison with (99m)Tc-MIBI.
AB  - We have previously shown enhanced accumulation of the delocalized lipophilic
      cation (11)C-triphenylmethylphosphonium in canine brain glioma, suggesting its
      potential use for tumor staging in humans using PET. Here, we extend our studies
      of phosphonium cations to nonbrain tumors and characterize the biodistribution
      and tumor specificity of (3)H-tetraphenylphosphonium ((3)H-TPP) in non-small cell
      lung carcinoma in mice. METHODS: (3)H-TPP accumulation in isolated malignant lung
      nodules of the Lewis lung carcinoma (LLC) cell line, in LLC-bearing lung, and in
      control lung was measured at various intervals after inoculation. Tumor uptake
      and biodistribution of (3)H-TPP were compared with those of (99m)Tc
      methoxyisobutylisonitrile (MIBI). RESULTS: (3)H-TPP accumulation in LLC nodules
      at 14 d was significantly greater than that in controls, peaked at 21 d, and
      declined to lower values at 28 d after injection. At 21 d after injection, (3)H
      TPP uptake in LLC nodules was greater than that in control lung tissue and in LLC
      bearing lung tissue-by 549% and 230%, respectively-whereas (99m)Tc-MIBI nodule
      uptake was greater by 90% and 30%, respectively. CONCLUSION: The high tumor
      accumulation and sensitivity to the phase of tumor development suggest the
      potential use of radiolabeled phosphonium analogs for in vivo tumor staging and
      as a tool for investigating tumor evolution.

PMID- 11850491
TI  - Evaluation of (99m)Tc-ciprofloxacin scintigraphy in a rabbit model of
      Staphylococcus aureus prosthetic joint infection.
AB  - Ciprofloxacin, a quinolone antibiotic drug, binds to DNA topoisomerase IV and DNA
      gyrase of various bacteria. Thus ciprofloxacin labeled with (99m)Tc could
      potentially act as a specific marker allowing discrimination between infection
      and sterile inflammation. We evaluated these properties on a rabbit model of
      prosthetic joint infection previously validated. We compared the images obtained
      in 2 groups of animals: rabbits with infected (G1; n = 6) and uninfected (G2; n =
      7) prosthesis. METHODS: Partial right-knee arthroplasty was performed on 13 New
      Zealand White female rabbits, with a tibial silicone-elastomer implant fitting
      into the intramedullary canal of the tibia. After the surgical wound was closed,
      10(7) cfu of a clinical strain of methicillin-susceptible Staphylococcus aureus
      were injected into the joint in G1 rabbits. G2 rabbits were injected with sterile
      saline. No antibiotic therapy was given to the animals. (99m)Tc-ciprofloxacin
      planar imaging was performed on days 5, 12, and 19 after surgery, and after 3 mo
      in 1 uninfected rabbit. Images were obtained 1, 4, and 24 h after injection (147
      +/- 13 MBq). RESULTS: In G1, increased right knee (99m)Tc-ciprofloxacin uptake
      was observed in 3 of 5 rabbits on day 5, and in all cases on days 12 and 19.
      Killing of the animals revealed purulent arthritis, osteitis, and tibial
      myelitis. In G2, significant right-knee uptake was found on days 12 and 19 in 5
      of 6 rabbits, and after 3 mo in 1; all sets of images were negative in 1 animal.
      Bacteriologic studies after the animals were killed were negative in G2. Mean
      right/left knee uptake ratios on day 19 (4-h images) were 1.8 +/- 0.4 in G1
      versus 1.4 +/- 0.3 in G2 (not significant). Late images did not discriminate
      between infected and uninfected arthroplasty. CONCLUSION: Results of (99m)Tc
      ciprofloxacin imaging in rabbits with infected/uninfected knee prosthesis suggest
      good sensitivity but lack of specificity for the detection of S. aureus
      infection.

PMID- 11850492
TI  - 99mTc-mebrofenin scintigraphy for evaluating liver disease in a rat model of
      Wilson's disease.
AB  - The purpose of this study was to establish whether (99m)Tc-mebrofenin could
      noninvasively assess liver function in Wilson's disease. METHODS: Long-Evans
      Cinnamon (LEC) rats, which reproduce Wilson's disease with copper toxicosis, and
      their normal counterparts, Long-Evans Agouti (LEA) rats, were studied.
      Scintigraphic findings were correlated with biliary mebrofenin excretion and
      residual organ counts and with hepatic copper content, histology, copper
      excretion capacity, and liver test results. RESULTS: Serum alanine
      aminotransferase (ALT) levels were elevated in some LEC rats, whereas serum
      bilirubin levels were normal. Liver histology was normal in LEA rats, whereas LEC
      rats showed multiple abnormalities. Mebrofenin was incorporated rapidly in LEA
      rats, with a mean time to peak liver activity of 80 +/- 30 s, followed by prompt
      biliary excretion of the tracer. In LEC rats, the mean time to peak activity, 283
      +/- 190 s, was significantly longer (P = 0.001). The time to half of peak
      activity, indicating tracer clearance, was significantly greater in LEC rats than
      in LEA rats (1,825 +/- 1,642 s vs. 524 +/- 82 s, P = 0.002). Hepatic mebrofenin
      handling correlated with hepatic copper content, histologic grade, copper
      excretion capacity, and serum ALT. CONCLUSION: Correlation of (99m)Tc-mebrofenin
      handling with liver morphology, function, and copper accumulation in LEC rats
      suggests that mebrofenin scintigraphy can be useful for noninvasively monitoring
      disease progression and therapeutic response in Wilson's disease. Although the
      data were obtained in an animal model of Wilson' disease, these biochemical
      parameters likely reflect liver damage in general, suggesting that there may be a
      role for mebrofenin scintigraphy in other chronic liver diseases as well.

PMID- 11850493
TI  - Evaluating early dementia with and without assessment of regional cerebral
      metabolism by PET: a comparison of predicted costs and benefits.
AB  - Evaluating dementia in patients with early symptoms of cognitive decline is
      clinically challenging. Growing evidence indicates that appropriate incorporation
      of PET into the clinical work-up can improve diagnostic and prognostic accuracy
      with respect to Alzheimer's disease (AD), the most common cause of dementia in
      the geriatric population. The precise diagnostic role of PET and its economic
      impact in this context, however, have not been systematically examined
      previously. METHODS: We compared the relative value of 2 strategies for assessing
      whether early AD is responsible for cognitive symptoms in geriatric patients: (a)
      a conventional approach, based largely on establishing clinical criteria for the
      presence of dementia and excluding non-AD etiologies that could contribute to the
      patient's symptoms, and (b) a proposed approach using PET to examine regional
      cerebral metabolism and look for characteristic patterns of abnormal metabolism.
      The total costs (measured in dollars) and benefits (measured in number of
      accurate diagnoses) of diagnostic testing and clinical outcomes accruing to each
      strategy were calculated using formalized tools of decision analysis. The primary
      outcome measure by which the strategies were compared was the ratio of costs to
      benefits obtained following each approach. RESULTS: Following the proposed
      approach led to improved accuracy in identifying early AD, without adding to the
      overall costs of diagnosis and treatment ($3,433 vs. $3,564 per patient
      approached by the proposed or conventional algorithm, respectively). The strategy
      making use of PET was associated with a reduced rate of false-negative and false
      positive findings compared with the conventional approach (3.1% vs. 8.2% and
      12.0% vs. 23.0%, respectively, at a prevalence of 51.6% in the studied
      symptomatic population) and a cost savings of $1,138 per correct diagnosis
      rendered ($4,047 vs. $5,185). The lower cost per unit benefit for the proposed
      strategy was maintained over a wide range of tested values for variables of
      sensitivity, specificity, costs of PET and long-term care, and varying approaches
      to the use of structural neuroimaging. CONCLUSION: Appropriate use of PET for
      evaluating early dementia in geriatric patients can add valuable information to
      the clinical work-up, without adding to the overall costs of evaluation and
      management, resulting in a greater number of patients being accurately diagnosed
      for the same level of financial expenditure. Thus, the opportunity exists for
      diminishing the morbidity of dementia economically, with earlier institution of
      more appropriate management in evaluated patients.

PMID- 11850494
TI  - Administration guidelines for radioimmunotherapy of non-Hodgkin's lymphoma with
      (90)Y-labeled anti-CD20 monoclonal antibody.
AB  - 90Y-ibritumomab tiuxetan is a novel radioimmunotherapeutic agent recently
      approved for the treatment of relapsed or refractory low-grade, follicular, or
      CD20+ transformed non-Hodgkin's lymphoma (NHL). (90)Y-ibritumomab tiuxetan
      consists of a murine monoclonal antibody covalently attached to a metal chelator,
      which stably chelates (111)In for imaging and (90)Y for therapy. Both health care
      workers and patients receiving this therapy need to become familiar with how it
      differs from conventional chemotherapy and what, if any, safety precautions are
      necessary. Because (90)Y is a pure beta-emitter, the requisite safety precautions
      are not overly burdensome for health care workers or for patients and their
      families. (90)Y-ibritumomab tiuxetan is dosed on the basis of the patient's body
      weight and baseline platelet count; dosimetry is not required for determining the
      therapeutic dose in patients meeting eligibility criteria similar to those used
      in clinical trials, such as <25% lymphomatous involvement of the bone marrow.
      (111)In- and (90)Y-ibritumomab tiuxetan are labeled at commercial radiopharmacies
      and delivered for on-site dose preparation and administration. Plastic and
      acrylic materials are appropriate for shielding during dose preparation and
      administration; primary lead shielding should be avoided because of the potential
      exposure risk from bremsstrahlung. Because there are no penetrating gamma
      emissions associated with the therapy, (90)Y-ibritumomab tiuxetan is routinely
      administered on an outpatient basis. Furthermore, the risk of radiation exposure
      to patients' family members has been shown to be in the range of background
      radiation, even without restrictions on contact. There is therefore no need to
      determine activity limits or dose rate limits before patients who have been
      treated with (90)Y radioimmunotherapy are released, as is necessary with patients
      who have been treated with radiopharmaceuticals that contain (131)I. Standard
      universal precautions for handling body fluids are recommended for health care
      workers and patients and their family members after (90)Y-ibritumomab tiuxetan
      administration. In summary, (90)Y-ibritumomab tiuxetan introduces (90)Y into
      clinical practice and expands the role nuclear medicine plays in the care of
      patients with cancer. Understanding the unique properties of this novel
      radioimmunoconjugate will facilitate its safe and effective use.

PMID- 11850496
TI  - Pumps and leaks in the heart.

PMID- 11850497
TI  - Regulation of the glutamine transporter SN1 by extracellular pH and intracellular
      sodium ions.
AB  - The glutamine transporter SN1 has recently been identified as one of the major
      glutamine transporters in hepatocytes and brain astrocytes. It appears to be the
      molecular correlate of system N amino acid transport. Two different transport
      mechanisms have been proposed for this transporter. These are an electroneutral
      mechanism, in which glutamine uptake is coupled to an exchange of 1Na+ and 1H+,
      or an electrogenic mechanism coupled to the exchange of 2Na+ against 1H+. This
      study was performed to solve these discrepancies and to investigate the
      reversibility of the transporter. When SN1 was expressed in Xenopus laevis
      oocytes, glutamine uptake was accompanied by a cotransport of 2-3 Na+ ions as
      determined by 22Na+ fluxes. However, at the same time a rapid release of
      intracellular Na+ was observed indicating an active exchange of Na+ ions. The
      driving force of the proton electrochemical gradient was equivalent to that of
      the sodium electrochemical gradient. Acidification of the extracellular medium
      caused the transporter to run in reverse and to release glutamine. Determination
      of accumulation ratios at different driving forces were in agreement with an
      electroneutral 1Na+-glutamine cotransport-1H+ antiport. Inward currents that were
      observed during glutamine uptake were much smaller than expected for a
      stoichiometric cotransport of charges. A slippage mode in the transporter
      mechanism and pH-regulated endogenous oocyte cation channels are likely to
      contribute to the observed currents.

PMID- 11850498
TI  - Fast Ca2+ signals at mouse inner hair cell synapse: a role for Ca2+-induced Ca2+
      release.
AB  - Inner hair cells of the mammalian cochlea translate acoustic stimuli into 'phase
      locked' nerve impulses with frequencies of up to at least 1 kHz. Little is known
      about the intracellular Ca2+ signal that links transduction to the release of
      neurotransmitter at the afferent synapse. Here, we use confocal microscopy to
      provide evidence that Ca2+-induced Ca2+ release (CICR) may contribute to the
      mechanism. Line scan images (2 ms repetition rate) of neonatal mouse inner hair
      cells filled with the fluorescent indicator FLUO-3, revealed a transient increase
      in intracellular Ca2+ concentration ([Ca2+]i) during brief (5-50 ms) depolarizing
      commands under voltage clamp. The amplitude of the [Ca2+]i transient depended
      upon the Ca2+ concentration in the bathing medium in the range 0-1.3 mM. [Ca2+]i
      transients were confined to a region near the plasma membrane at the base of the
      cell in the vicinity of the afferent synapses. The change in [Ca2+]i appeared
      uniform throughout the entire basal sub-membrane space and we were unable to
      observe hotspots of activity. Both the amplitude and the rate of rise of the
      [Ca2+]i transient was reduced by external ryanodine (20 microM), an agent that
      blocks Ca2+ release from the endoplasmic reticulum. Intracellular Cs+, commonly
      used to record at presynaptic sites, produced a similar effect. We conclude that
      both ryanodine and intracellular Cs+ block CICR in inner hair cells. We discuss
      the contribution of CICR to the measured [Ca2+]i transient, the implications for
      synaptic transmission at the afferent synapse and the significance of its
      sensitivity to intracellular Cs+.

PMID- 11850499
TI  - Effect of nitric oxide donors and noradrenaline on Ca2+ release sites and global
      intracellular Ca2+ in myocytes from guinea-pig small mesenteric arteries.
AB  - In smooth muscle the spontaneous Ca2+ release from the sarcoplasmic reticulum
      (SR) occurs at preferred locations called frequent discharge sites (FDSs) giving
      rise to localized intracellular Ca2+ transients (Ca2+ sparks). Laser scanning
      confocal microscopy of fluo-3-loaded single myocytes freshly isolated from small
      mesenteric arteries of guinea-pig was used to investigate the action of nitric
      oxide (NO) donors and noradrenaline on the position and activity of FDSs and on
      global intracellular Ca2+ concentration ([Ca2+]i). In 8 % of cells 'microsparks',
      Ca2+ release events smaller in duration, spread and amplitude than Ca2+ sparks
      were observed. The location of the initiation point of Ca2+ sparks observed
      during line-scan imaging was found to 'jitter' by +/- 0.41 microm. However, the
      general position of an FDS within the cell did not change; most FDSs were close
      (within 1.2 +/- 0.1 microm) to the cell membrane and often multiple FDSs occurred
      in one confocal plane of the cell. In the resting state, NO donors S-nitroso-N
      acetylpenicillamine (SNAP; 50 microM) and sodium nitroprusside (SNP; 100 microM)
      did not change the general position of FDSs and slightly depressed their
      activity, but did not affect the global [Ca2+]i significantly. Application of
      noradrenaline (1-10 microM) increased Ca2+ spark frequency at existing FDS(s)
      leading to a Ca2+ wave. The increase in FDS activity and in global [Ca2+]i
      produced by noradrenaline were inhibited by the presence of SNAP or SNP but not
      by 8-bromoguanosine cyclic 3',5'-monophosphate (8-Br-cGMP; 100 microM). In the
      presence of 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), inhibitor of
      soluble guanylate cyclase, SNAP and SNP still exerted their effects on the
      noradrenaline response. These results suggest that SNAP and SNP inhibit the
      noradrenaline-evoked rise in global [Ca2+]i by a cGMP-independent mechanism and
      that part of this effect is due to inhibition of the activity of FDSs; moreover,
      only the activity, but not the position, of FDSs is changed by either stimulant
      or inhibitory substances.

PMID- 11850500
TI  - Correlation of NADH and Ca2+ signals in mouse pancreatic acinar cells.
AB  - Relationships between calcium signals and NADH responses were investigated in
      pancreatic acinar cells stimulated with calcium-releasing secretagogues.
      Cytosolic calcium signals were studied using Fura Red or calcium-sensitive Cl(-)
      current. Mitochondrial calcium was measured using Rhod-2. The highest levels of
      NADH autofluorescence were found around the secretory granule region. Stimulation
      of cells with physiological doses of cholecystokinin (CCK) triggered slow
      oscillations of NADH autofluorescence. NADH oscillations were clearly resolved in
      the mitochondrial clusters around secretory granules. Very fast apical calcium
      signals induced by acetylcholine (ACh) produced no detectable changes in NADH;
      slightly more extended apical (or preferentially apical) calcium transients
      triggered clear NADH responses. Triple combined recordings of cytosolic calcium,
      mitochondrial calcium and NADH revealed the sequence of development of individual
      signals: an increase in cytosolic calcium was accompanied by a slower
      mitochondrial calcium response followed by a delayed increase in NADH
      fluorescence. Recovery of cytosolic calcium was faster than recovery of
      mitochondrial calcium. NADH recovery occurred at elevated mitochondrial calcium
      levels. During the transient cytosolic calcium oscillations induced by
      intermediate doses of ACh, there was an initial increase in NADH fluorescence
      following the first calcium transient; each of the subsequent calcium responses
      produced biphasic NADH changes comprising an initial small decline followed by
      restoration to an elevated calcium level. During the higher-frequency sinusoidal
      calcium oscillations induced by higher doses of ACh, NADH responses fused into a
      smooth rise followed by a slow decline. Supramaximal doses of ACh and CCK
      produced single large NADH transients.

PMID- 11850501
TI  - Development of Ca2+ hotspots between Lymnaea neurons during synaptogenesis.
AB  - Calcium (Ca2+) channel clustering at specific presynaptic sites is a hallmark of
      mature synapses. However, the spatial distribution patterns of Ca2+ channels at
      newly formed synapses have not yet been demonstrated. Similarly, it is unclear
      whether Ca2+ 'hotspots' often observed at the presynaptic sites are indeed target
      cell contact specific and represent a specialized mechanism by which Ca2+
      channels are targeted to select synaptic sites. Utilizing both soma-soma paired
      (synapsed) and single neurons from the mollusk Lymnaea, we have tested the
      hypothesis that differential gradients of voltage-dependent Ca2+ signals develop
      in presynaptic neuron at its contact point with the postsynaptic neuron; and that
      these Ca2+ hotspots are target cell contact specific. Fura-2 imaging, or two
      photon laser scanning microscopy of Calcium Green, was coupled with
      electrophysiological techniques to demonstrate that voltage-induced Ca2+
      gradients (hotspots) develop in the presynaptic cell at its contact point with
      the postsynaptic neuron, but not in unpaired single cells. The incidence of Ca2+
      hotspots coincided with the appearance of synaptic transmission between the
      paired cells, and these gradients were target cell contact specific. In contrast,
      the voltage-induced Ca2+ signal in unpaired neurons was uniformly distributed
      throughout the somata; a similar pattern of Ca2+ gradient was observed in the
      presynaptic neuron when it was soma-soma paired with a non-synaptic partner cell.
      Moreover, voltage clamp recording techniques, in conjunction with a fast, optical
      differential perfusion system, were used to demonstrate that the total whole-cell
      Ca2+ (or Ba2+) current density in single and paired cells was not significantly
      different. However, the amplitude of Ba2+ current was significantly higher in the
      presynaptic cell at its contact side with the postsynaptic neurons, compared with
      non-contacted regions. In summary, this study demonstrates that voltage-induced
      Ca2+ hotspots develop in the presynaptic cell, concomitant with the appearance of
      synaptic transmission between the soma-soma paired cells. The appearance of Ca2+
      gradients in presynaptic neurons is target cell contact specific and is probably
      due to a spatial redistribution of existing channels during synaptogenesis.

PMID- 11850502
TI  - Phasic and tonic attenuation of EPSPs by inward rectifier K+ channels in rat
      hippocampal pyramidal cells.
AB  - We made whole-cell recordings from CA1 pyramidal cells of hippocampal slices in
      combination with brief dendritic glutamate pulses to study the role of
      constitutive inwardly rectifying K+ channels (IRK, Kir2.0) and G-protein
      activated inwardly rectifying K+ channels (GIRK, Kir3.0) in the processing of
      excitatory inputs. Phasic activation of GIRK channels by baclofen (20 microM)
      produced a reversible reduction of glutamate-evoked postsynaptic potentials
      (GPSPs), our equivalent of EPSPs, by about one-third. Conversely, tertiapin (30
      nM), a selective inhibitor of GIRK channels, and Ba2+ (200 microM), a non
      selective blocker of inwardly rectifying K+ channels, enhanced GPSPs and, in
      voltage-clamp experiments, reduced the underlying K+ conductances, indicating a
      functionally significant background GIRK conductance, in addition to constitutive
      IRK channel activity. When examined after suppression of endogenous adenosinergic
      inhibition, using either adenosine deaminase or the selective A1 receptor
      antagonist, 1,3-dipropyl-8-cyclopentylxanthine, tertiapin failed to influence
      either the GPSPs or the inwardly rectifying K+ conductance. Voltage-clamp
      recordings from acutely isolated CA1 pyramidal cells not exposed to ambient
      adenosine exhibited no response to tertiapin, whereas Ba2+ was still capable of
      reducing hyperpolarizing inward rectification. Our data indicate that in
      hippocampal pyramidal cells, two components of the inwardly rectifying K+
      conductance can be identified, which together exert a tonic modulation of
      excitatory synaptic input: one arises from constitutive putative IRK channels,
      the other is mediated by the background activity of GIRK channels that results
      from the tonic activation of A1 receptors by ambient adenosine.

PMID- 11850503
TI  - Nitric oxide inhibits capacitative Ca2+ entry and enhances endoplasmic reticulum
      Ca2+ uptake in bovine vascular endothelial cells.
AB  - In vascular endothelial cells, elevation of cytosolic free calcium concentration
      ([Ca2+]i) causes activation of nitric oxide synthase (NOS) and release of nitric
      oxide (NO). The goal of the study was to characterize the interplay between
      [Ca2+]i and NO production in this cell type. Simultaneous measurements of [Ca2+]i
      and intracellular NO concentration ([NO]i) in cultured bovine vascular
      endothelial cells (CPAE cell line) with the fluorescent indicators fura-2 and DAF
      2, respectively, revealed that Ca2+ influx following agonist-induced
      intracellular Ca2+ store depletion (capacitative Ca2+ entry, CCE) represents the
      preferential Ca2+ source for the activation of the Ca2+-calmodulin-dependent
      endothelial NOS (eNOS). Exposure to the NO donor sodium nitroprusside (SNP)
      showed that high NO levels suppressed CCE and had an inhibitory effect on Ca2+
      extrusion by the plasmalemmal Ca2+-ATPase. This inhibitory effect on CCE was
      mimicked by the membrane-permeant cGMP analogue 8-bromo-cGMP, but was reversed by
      the NO scavenger haemoglobin and prevented by the inhibitor of the NO-sensitive
      guanylate cyclase ODQ. Brief exposure to SNP reduced the peak of ATP-induced Ca2+
      release from the endoplasmic reticulum (ER) and accelerated Ca2+ reuptake into
      the ER. Prolonged incubation with SNP resulted in enhanced Ca2+ loading of the
      ER, as revealed by direct measurements of store content with the ER-entrapped low
      affinity Ca2+ indicator mag-fura-2. The results suggest that in vascular
      endothelial cells, NO synthesis is under autoregulatory control that involves NO
      dependent [Ca2+]i regulation. Via cGMP-dependent inhibition of CCE and
      acceleration of Ca2+ sequestration into the ER, NO can lower [Ca2+]i and
      therefore exert an autoregulatory negative feedback on its own Ca2+-dependent
      synthesis.

PMID- 11850504
TI  - Effects of inhibitors of the lipo-oxygenase family of enzymes on the store
      operated calcium current I(CRAC) in rat basophilic leukaemia cells.
AB  - In non-excitable cells, the major Ca2+ entry pathway is the store-operated
      pathway in which emptying of intracellular Ca2+ stores activates Ca2+ channels in
      the plasma membrane. In many cell types, store-operated influx gives rise to a
      Ca2+-selective current called I(CRAC) (Ca2+ release-activated Ca2+ current).
      Using both the whole-cell patch clamp technique to measure I(CRAC) directly and
      fluorescent Ca2+ imaging, we have examined the role of the lipo-oxygenase pathway
      in the activation of store-operated Ca2+ entry in the RBL-1 rat basophilic
      leukaemia cell-line. Pretreatment with a variety of structurally distinct lipo
      oxygenase inhibitors all reduced the extent of I(CRAC), whereas inhibition of the
      cyclo-oxygenase enzymes was without effect. The inhibition was still seen in the
      presence of the broad protein kinase blocker staurosporine, or when Na+ was used
      as the charge carrier through CRAC channels. The lipo-oxygenase blockers released
      Ca2+ from intracellular stores but this was not associated with subsequent Ca2+
      entry. Lipo-oxygenase blockers also reduced both the amount of Ca2+ that could
      subsequently be released by the combination of thapsigargin and ionomycin in Ca2+
      free solution and the Ca2+ influx component that occurred when external Ca2+ was
      re-admitted. The inhibitors were much less effective if applied after I(CRAC) had
      been activated. This inhibition of I(CRAC) could not be rescued by dialysis with
      5(S)-hydroxyperoxyeicosa-6E,8Z,11Z,14Z,tetraenoic acid (5-HPETE), the first
      product of the 5-lipo-oxygenase pathway. Our findings indicate that exposure to
      pharmacological tools that inhibit the lipo-oxygenase enzymes all decrease the
      extent of activation of the current. Our results raise the possibility that a
      lipo-oxygenase might be involved in the activation of I(CRAC). Alternative
      explanations are also discussed.

PMID- 11850505
TI  - Comparison of the properties of CLCA1 generated currents and I(Cl(Ca)) in murine
      portal vein smooth muscle cells.
AB  - Calcium-activated chloride currents (I(Cl(Ca))) have been recorded in various
      smooth muscle cells but, to date, there has been no information as to the
      molecular nature of the channel underlying this conductance. We have
      characterised native I(Cl(Ca)) in freshly dispersed smooth muscle cells isolated
      from murine portal vein using whole-cell voltage clamp. I(Cl(Ca)) exhibited time
      dependent activation at depolarised potentials and rapid deactivation upon
      repolarisation. The reversal potential of I(Cl(Ca)) was close to the theoretical
      equilibrium potential (E(Cl)) and was shifted by replacement of external Cl- by
      SCN- or isethionate. Dithiothreitol (DTT, 1 mM), a blocker of CLCA1, had no
      effect on the I(Cl(Ca)) current in myocytes. RT-PCR demonstrated the expression
      of mCLCA1 transcripts, but not mCLCA3 transcripts, in various murine smooth
      muscle cells including portal vein, as well as cardiomyocytes, and the levels of
      mCLCA1 transcriptional expression were quantified by real time quantitative RT
      PCR. Stable transfection of HEK293 cells with the cDNA encoding mCLCA1 cloned
      from murine portal vein smooth muscle yielded a current with notable differences
      in Ca2+ sensitivity, channel kinetics and modulation by DTT from the native
      I(Cl(Ca)). However, there was some similarity in the pore properties and these
      data suggest that mCLCA1 alone does not comprise the Cl- channel in portal vein
      smooth muscle cells.

PMID- 11850506
TI  - Dual effect of blocking agents on Ca2+-activated Cl(-) currents in rabbit
      pulmonary artery smooth muscle cells.
AB  - The effects of the Cl- channel antagonists, niflumic acid (NFA), dichloro
      diphenylamine 2-carboxylic acid (DCDPC) and diisothiocyanato-stilbene-2,2'
      disulphonic acid (DIDS) on Ca2+-activated Cl- current (I(Cl(Ca))) evoked by
      adding fixed intracellular calcium concentrations ([Ca2+]i) to the pipette
      solution were studied in rabbit pulmonary artery myocytes. With 250 and 500 nM
      [Ca2+]i bath application of NFA (100 microM) increased inward current at negative
      potentials, but inhibited outward current at positive potentials. On wash out of
      NFA, I(Cl(Ca)) was greatly enhanced at all potentials. When external Na+ ions
      were replaced by N-methyl-D-glucamine (NMDG+) NFA still enhanced I(Cl(Ca)) at
      negative potentials but the increase of I(Cl(Ca)) on wash out was blocked. When
      the mean reversal potential (E(r)) of I(Cl(Ca)) was shifted to negative
      potentials by replacing external Cl- with SCN-, NFA increased inward current but
      blocked outward current suggesting that the effect of NFA is dependent on current
      flow. Inclusion of NFA in the pipette solution had no effect on I(Cl(Ca)).
      Voltage jump experiments indicated that I(Cl(Ca)) displayed characteristic
      outward current relaxations at +70 mV and inward current relaxations at -80 mV
      that were abolished by NFA. DCDPC (100 microM) produced similar effects to NFA
      but 1 mM DIDS produced inhibition of I(Cl(Ca)) at both positive and negative
      potentials and there was no increase in current on wash out of DIDS. These
      results suggest that NFA and DCDPC, but not DIDS, simultaneously enhance and
      block I(Cl(Ca)) by binding to an external site, probably close to the mouth of
      the chloride channel.

PMID- 11850507
TI  - Intracellular [Na+] and Na+ pump rate in rat and rabbit ventricular myocytes.
AB  - Intracellular [Na+] ([Na+]i) is centrally involved in regulation of cardiac Ca2+
      and contractility via Na+-Ca2+ exchange (NCX) and Na+-H+ exchange (NHX). Previous
      work has indicated that [Na+]i is higher in rat than rabbit ventricular myocytes.
      This has major functional consequences, but the reason for the higher [Na+]i in
      rat is unknown. Here, resting [Na+]i was measured using the fluorescent indicator
      SBFI, with both traditional calibration and a novel null-point method (which
      circumvents many limitations of prior methods). In rabbit, resting [Na+]i was 4.5
      +/- 0.4 mM (traditional calibration) and 4.4 mM (null-point). Resting [Na+]i in
      rat was significantly higher using both the traditional calibration (11.1 +/- 0.7
      mM) and the null-point approach (11.2 mM). The rate of Na+ transport by the Na+
      pump was measured as a function of [Na+]i in intact cells. Rat cells exhibited a
      higher V(max) than rabbit (7.7 +/- 1.1 vs. 4.0 +/- 0.5 mM x min(-1)) and a higher
      K(m) (10.2 +/- 1.2 vs. 7.5 +/- 1.1 mM). This results in little difference in pump
      activity for a given [Na+]i below 10 mM, but at measured resting [Na+]i levels
      the pump-mediated Na+ efflux is much higher in rat. Thus, Na+ pump rate cannot
      explain the higher [Na+]i in rat. Resting Na+ influx rate was two to four times
      higher in rat, and this accounts for the higher resting [Na+]i. Using
      tetrodotoxin, HOE-642 and Ni2+ to block Na+ channels, NHX and NCX, respectively,
      we found that all three pathways may contribute to the higher resting Na+ influx
      in rat (albeit differentially). We conclude that resting [Na+]i is higher in rat
      than in rabbit, that this is caused by higher resting Na+ influx in rat and that
      a higher Na+,K+-ATPase pumping rate in rat is a consequence of the higher [Na+]i.

PMID- 11850508
TI  - Role of ATP decrease in secretion induced by mitochondrial dysfunction in guinea
      pig adrenal chromaffin cells.
AB  - The mechanism related to mitochondrial dysfunction-induced catecholamine (CA)
      secretion in dispersed guinea-pig adrenal chromaffin cells was investigated using
      amperometry and confocal laser microscopy. Application of CCCP, which does not
      stimulate generation of reactive oxygen species (ROS), reversibly induced CA
      secretion, whereas application of either cyanide or oligomycin (OL), a stimulator
      for ROS, enhanced CA secretion to a smaller extent. The CCCP-induced secretion
      was abolished by removal of external Ca2+ ions and was markedly diminished by
      D600. The mitochondrial membrane potential, measured using rhodamine 123, was
      rapidly lost in response to CCCP, but did not change noticeably during a 3 min
      exposure to OL. Prior exposure to OL markedly facilitated depolarization of the
      mitochondrial membrane potential in response to cyanide. The mitochondrial
      inhibitors rapidly produced an increase in Magnesium Green (MgG) fluorescence in
      the absence of external Ca2+ and Mg2+ ions, an increase that was larger in the
      cytoplasm than in the nucleus. The rank order of potency in increasing MgG
      fluorescence among the inhibitors was similar to that in increasing secretion.
      Thus, mitochondrial inhibition rapidly decreases [ATP] and the mitochondrial
      dysfunction-induced secretion is not due to ROS generation or to mitochondrial
      depolarization, but is possibly mediated by a decrease in ATP.

PMID- 11850509
TI  - Group II metabotropic glutamate receptor activation is required for normal
      hippocampal mossy fibre development in the rat.
AB  - Glutamate is the main neurotransmitter at hippocampal mossy fibre (MF) terminals.
      Because neurotransmitters have been proposed as regulating factors of neural
      network formation and neurite morphogenesis in the developing CNS, we examined
      the possible contribution of glutamate to MF pathfinding. Entorhino-hippocampal
      slices prepared from early postnatal rats were cultivated in the presence of
      glutamate receptor antagonists. Timm histochemical staining revealed that
      pharmacological blockade of metabotropic glutamate receptors (mGluR), but not of
      ionotropic glutamate receptors, induced abnormal outgrowth of the MFs. When
      slices were cultured in the presence of mGluR antagonists, DiI-labelled MF axons
      displayed a great degree of defasciculation, and MF-mediated EPSPs in the CA3
      pyramidal cells were altered. Similar results were obtained for a selective
      antagonist of group II mGluR, but not of group I or III mGluR. Glutamate is,
      therefore, likely to regulate MF outgrowth via activation of group II mGluR. The
      present study may provide a novel role of glutamate in hippocampal development.

PMID- 11850510
TI  - Effects of butyrate on active sodium and chloride transport in rat and rabbit
      distal colon.
AB  - Short chain fatty acids, particularly butyrate, stimulate electroneutral NaCl
      absorption from the colon. Their effect in colonic epithelia lacking basal
      electroneutral NaCl absorption is unknown. Butyrate is also reported to inhibit
      active Cl- secretion in the colon. The present studies were undertaken to
      investigate the inter-relationships between the effects of butyrate on active Na+
      and Cl- transport in the colon. Studies were carried out in rabbit distal colon
      (known to have predominant electrogenic Na+ absorption), rat distal colon
      (characterised by electroneutral Na+ absorption), and hyperaldosteronaemic rat
      distal colon (characterised by electrogenic Na+ absorption). The effect of
      cholera toxin (CT) was also noted. Potential difference, short-circuit current
      (I(SC)) and fluxes of Na+ and Cl- were measured in stripped mucosa under voltage
      clamp conditions. Butyrate stimulated electroneutral Na+ and Cl- absorption in
      distal colon of normal and salt-depleted rats, and stimulated Na+ absorption in
      rabbit distal colon. Amiloride (10(-4) M) or CT did not inhibit this process. In
      rabbit distal colon, stimulation of Na+ absorption by butyrate was not dependent
      on the presence of Cl- in the medium. Butyrate significantly decreased
      conductance, decreased flux of sodium from serosa to mucosa (particularly in
      rabbit distal colon), and decreased I(SC). Net Cl- secretion, induced by CT, was
      completely inhibited by butyrate. Stimulation of Na+ absorption was independent
      of exposure to CT. Bumetanide reversed net Cl- secretion to net absorption, but
      did not alter Na+ or Cl- fluxes in tissues exposed to butyrate. Thus butyrate
      stimulates active Na+ absorption in colonic epithelia, with or without expression
      of basal Na+-H+ exchange. Independently, butyrate inhibits active Cl- secretion
      induced by cAMP in these epithelia.

PMID- 11850511
TI  - Chloride transport in microperfused interlobular ducts isolated from guinea-pig
      pancreas.
AB  - Isolated interlobular ducts from the guinea-pig pancreas secrete a HCO3--rich
      fluid in response to secretin. To determine the role of Cl- transporters in this
      process, intracellular Cl- concentration ([Cl-]i) was measured in ducts loaded
      with the Cl--sensitive fluoroprobe, 6-methoxy-N-ethylquinolinium chloride (MEQ).
      [Cl-]i decreased when the luminal Cl- concentration was reduced. This effect was
      stimulated by forskolin, was not dependent on HCO3- and was not inhibited by
      application of the anion channel/transporter inhibitor H2DIDS to the luminal
      membrane. It is therefore attributed to a cAMP-stimulated Cl- conductance,
      probably the cystic fibrosis transmembrane conductance regulator (CFTR) Cl-
      channel. [Cl-]i also decreased when the basolateral Cl- concentration was
      reduced. This effect was not stimulated by forskolin, was largely dependent on
      HCO3- and was inhibited by basolateral H2DIDS. It is therefore mediated mainly by
      Cl-/HCO3- exchange. With high Cl- and low HCO3- concentrations in the lumen,
      steady-state [Cl-]i was 25-35 mM in unstimulated cells. Stimulation with
      forskolin caused [Cl-]i to increase by approximately 4 mM due to activation of
      the luminal anion exchanger. With low Cl- and high HCO3- concentrations in the
      lumen to simulate physiological conditions, steady-state [Cl-]i was 10-15 mM in
      unstimulated cells. Upon stimulation with forskolin, [Cl-]i fell to approximately
      7 mM due to increased Cl- efflux via the luminal conductance. We conclude that,
      during stimulation under physiological conditions, [Cl-]i decreases to very low
      levels in guinea-pig pancreatic duct cells, largely as a result of the limited
      capacity of the basolateral transporters for Cl- uptake. The resulting lack of
      competition from intracellular Cl- may therefore favour HCO3- secretion via anion
      conductances in the luminal membrane, possibly CFTR.

PMID- 11850512
TI  - Beta-alanine and taurine as endogenous agonists at glycine receptors in rat
      hippocampus in vitro.
AB  - Electrophysiological and pharmacological properties of glycine receptors were
      characterized in hippocampal organotypic slice cultures. In the presence of
      ionotropic glutamate and GABA(B) receptor antagonists, pressure-application of
      glycine onto CA3 pyramidal cells induced a current associated with increased
      chloride conductance, which was inhibited by strychnine. Similar chloride
      currents could also be induced with beta-alanine or taurine. Whole-cell glycine
      responses were significantly greater in CA3 pyramidal cells than in CA1 pyramidal
      cells and dentate granule cells, while responses to GABA were similar among these
      three cell types. Although these results demonstrate the presence of functional
      glycine receptors in the hippocampus, no evidence for their activation during
      synaptic stimulation was found. Gabazine, a selective GABA(A) receptor
      antagonist, totally blocked evoked IPSCs in CA3 pyramidal cells. Glycine receptor
      activation is not dependent on transporter-controlled levels of extracellular
      glycine, as no chloride current was observed in response to sarcosine, an
      inhibitor of glycine transporters. In contrast, application of
      guanidinoethanesulfonic acid, an uptake inhibitor of beta-alanine and taurine,
      induced strychnine-sensitive chloride current in the presence of gabazine. These
      data indicate that modulation of transporters for the endogenous amino acids,
      beta-alanine and taurine, can regulate tonic activation of glycine receptors,
      which may function in maintenance of inhibitory tone in the hippocampus.

PMID- 11850513
TI  - Presynaptic short-term depression is maintained during regulation of transmitter
      release at a GABAergic synapse in rat hippocampus.
AB  - To examine possible interactions between fast depression and modulation of
      inhibitory synaptic transmission in the hippocampus, we recorded from pairs of
      synaptically connected basket cells (BCs) and granule cells (GCs) in the dentate
      gyrus of rat brain slices at 34 degrees C. Multiple-pulse depression (MPD) was
      examined in trains of 5 or 10 inhibitory postsynaptic currents (IPSCs) evoked at
      frequencies of 10-100 Hz under several conditions that inhibit transmitter
      release: block of voltage-dependent Ca2+ channels by Cd2+ (10 microM), activation
      of gamma-amino-butyric acid type B receptors (GABA(B)Rs) by baclofen (10 microM)
      and activation of muscarinic acetylcholine receptors (mAchRs) by carbachol (2
      microM). All manipulations led to a substantial inhibition of synaptic
      transmission, reducing the amplitude of the first IPSC in the train (IPSC1) by
      72%, 61% and 29%, respectively. However, MPD was largely preserved under these
      conditions (0.34 in control versus 0.31, 0.50 and 0.47 in the respective
      conditions at 50 Hz). Similarly, a theta burst stimulation (TBS) protocol reduced
      IPSC1 by 54%, but left MPD unchanged (0.40 in control and 0.39 during TBS).
      Analysis of both fractions of transmission failures and coefficients of variation
      (CV) of IPSC peak amplitudes suggested that MPD had a presynaptic expression
      site, independent of release probability. In conclusion, different types of
      presynaptic modulation of inhibitory synaptic transmission converge on a
      reduction of synaptic strength, while short-term dynamics are largely unchanged.

PMID- 11850514
TI  - Basolateral PAR-2 receptors mediate KCl secretion and inhibition of Na+
      absorption in the mouse distal colon.
AB  - Proteinase-activated receptor-2 (PAR-2) may participate in epithelial ion
      transport regulation. Here we examined the effect of mouse activating peptide
      (mAP), a specific activator of PAR-2, on electrogenic transport of mouse distal
      colon using short-circuit current (I(SC)) measurements. Under steady-state
      conditions, apical application of amiloride (100 microM) revealed a positive
      I(SC) component of 74.3 +/- 6.8 microA x cm(-2) indicating the presence of Na+
      absorption, while apical Ba2+ (10 mM) identified a negative I(SC) component of
      26.2 +/- 1.8 microA x cm(-2) consistent with K+ secretion. Baseline Cl- secretion
      was minimal. Basolateral addition of 20 microM mAP produced a biphasic I(SC)
      response with an initial transient peak increase of 11.2 +/- 0.9 microA x cm(-2),
      followed by a sustained fall to a level 31.2 +/- 2.6 microA x cm(-2) (n = 43)
      below resting I(SC). The peak response was due to Cl- secretion as it was
      preserved in the presence of amiloride but was largely reduced in the presence of
      basolateral bumetanide (20 microM) or in the absence of extracellular Cl-. The
      secondary decline of I(SC) was also attenuated by bumetanide and by Ba2+,
      indicating that it is partly due to a stimulation of K+ secretion. In addition,
      the amiloride-sensitive I(SC) was slightly reduced by mAP, suggesting that
      inhibition of Na+ absorption also contributes to the I(SC) decline. Expression of
      PAR-2 in mouse distal colon was confirmed using RT-PCR and immunocytochemistry.
      We conclude that functional basolateral PAR-2 is present in mouse distal colon
      and that its activation stimulates Cl- and K+ secretion while inhibiting baseline
      Na+ absorption.

PMID- 11850515
TI  - D1 and D2 receptor-mediated dopaminergic modulation of visual responses in cat
      dorsal lateral geniculate nucleus.
AB  - The modulatory effects of dopamine (DA) on the visual responses of relay cells of
      the dorsal aspect of cat lateral geniculate nucleus (dLGN) were tested using
      local micro-iontophoretic application of DA and application of the receptor
      specific agonists SKF38393 (SKF, D1/D5) and quinpirole (QUIN, D2/D3/D4) in the
      anaesthetized alcuronium-treated cat. The effects of DA and QUIN were clearly
      dose-dependent: small amounts caused a weak and transient facilitation of visual
      activity (10-30% increase) preferentially in Y-type relay cells, which changed to
      a moderate reduction of visual responses when the dose was increased (50%,
      maximal 70%). The effect of SKF was mainly suppressive and increased with the
      amount of drug applied (up to 90% reduction). The selective antagonists SCH23390
      (SCH, D1) and sulpiride (SULP, D2) reduced the effects of co-applied DA agonists.
      We found little evidence for a specific dopaminergic modulation of the surround
      inhibition (stimulus-driven lateral inhibition) although DA slightly facilitated
      the transmission of weak signals (small stimuli). Nevertheless, some dopaminergic
      effects seem to be mediated via inhibitory interneurons regulating the strength
      of sustained or recurrent inhibition. Application of DA agonists during blockade
      of GABA(A) receptors indicates a direct suppression of relay cells via D1
      receptors, an excitation of relay cells via D2 receptors and--with increasing
      amounts of D2 agonist--probably also an excitation of inhibitory interneurons,
      which results in an indirect inhibition of dLGN relay cells (predominantly of the
      X-type). The results are discussed in relation to the impairment of visual
      functions in Parkinson's disease.

PMID- 11850516
TI  - Non-linear, high-gain and sustained-to-transient signal transmission from rods to
      amacrine cells in dark-adapted retina of Ambystoma.
AB  - In darkness, On-Off amacrine cells (ACs) of the tiger salamander retina exhibited
      large spontaneous transient depolarizing potentials (sTDPs) with average peak
      amplitude of 5.05 +/- 2.5 mV and average frequency of 0.42 +/- 0.25 s(-1). Under
      voltage-clamp conditions the cell displayed large spontaneous postsynaptic
      currents (sPSCs) with average peak amplitude of 98 +/- 39 pA and average
      frequency of 0.45 +/- 0.22 s(-1). To a light step, ACs gave rise to a transient
      'On' response at the light onset and a transient 'Off' response at light offset,
      followed by a train of TDPs ('After' response). Near the response threshold (0.3
      activated rhodopsin molecules per rod per second), light-evoked TDPs (leTDPs) of
      similar amplitude and kinetics as the large sTDPs observed in darkness were seen,
      and about half of these leTDPs elicited a regenerative potential (RP). Brighter
      light steps gave rise to more leTDPs and higher rates of RPs in the On, Off and
      After responses. Within the linear response range of the rods, the AC response
      was non-linear, with the highest gain (676 +/- 429) near the dark potential. The
      amplitude of Off responses increased with the duration of the light step, and ACs
      may use this to encode speeds of moving stimuli: the faster the light object
      moves, the smaller the AC Off response. Moreover, the number of leTDPs in the AC
      After response increased with light intensity, and the onset of the After
      response coincides with bipolar cell tail response recovery. One possible origin
      of the large sTDPs and leTDPs is the spontaneous and depolarization-induced
      regenerative calcium potentials (RCaPs) in bipolar cell synaptic terminals. RCaPs
      in bipolar cell synaptic terminals cause transient glutamate release that results
      in the sTDPs in darkness, and leTDPs in On, Off and After responses in ACs.

PMID- 11850517
TI  - Calcium release and intramembranous charge movement in frog skeletal muscle
      fibres with reduced (< 250 microM) calcium content.
AB  - It is generally accepted that activation of voltage sensors in the T-tubular
      membranes is a critical step of excitation-contraction coupling in skeletal
      muscle. The purpose of this study was to evaluate further whether the Qgamma
      component (delayed 'hump' component) of the intramembranous charge movement
      current (I(cm)) results from movement of these voltage sensors. Ca2+ release and
      I(cm) were measured in voltage-clamped frog cut fibres mounted in a double
      Vaseline-gap chamber. In order to reduce effects of Ca2+ feedback mechanisms, the
      calcium content of the sarcoplasmic reticulum (SR) during rest was reduced to <
      250 microM (referred to volume of myoplasm) and maintained approximately
      constant. The early (Qbeta) and Qgamma components of charge movement were
      estimated by fitting the sum of two Boltzmann functions to the total steady-state
      intramembranous charge vs. voltage data. The average voltage steepness factor (k)
      and half-maximal voltage (V-) for Qgamma were 4.3 and -57.4 mV (n = 6),
      respectively. The SR membrane permeability for Ca2+ release was assessed when a
      constant amount of calcium remained in the SR (usually about 60 microM). A single
      Boltzmann function fitted to these data gave values on average for k and V- of
      4.7 and -45.3 mV, respectively. The similarity of the values of k for Qgamma and
      Ca2+ release supports the idea that Qgamma reflects movement of voltage sensors
      for Ca2+ release. The greater value of V- for Ca2+ release compared to Qgamma is
      consistent with multi-state models of the voltage sensor involving movement of
      Qgamma charge during non-activating transitions.

PMID- 11850518
TI  - Temperature effect on isometric tension is mediated by regulatory proteins
      tropomyosin and troponin in bovine myocardium.
AB  - The effect of temperature on isometric tension with and without the regulatory
      proteins tropomyosin and troponin was studied in bovine myocardium using a thin
      filament removal and reconstitution protocol. In control bovine myocardium,
      isometric tension increased linearly with temperature in the range 5-40 degrees
      C: isometric tension at 10 and 30 degrees C was 0.65 and 1.28 times that at 20
      degrees C, respectively, with a Q10 of about 1.4. In actin filament-reconstituted
      myocardium without regulatory proteins, the temperature effect on isometric
      tension was less: isometric tension at 10 and 30 degrees C was 0.96 and 1.17
      times that at 20 degrees C, respectively, with a Q10 of about 1.1. The
      temperature dependence of the apparent rate constants was studied using
      sinusoidal analysis. The temperature dependence of 2pi(b) (rate constant of
      delayed tension phase) did not vary significantly with the regulatory proteins
      under the standard activating condition (5 mM MgATP, 8 mM P(i), 200 mM ionic
      strength, pCa 4.66, pH 7.00). Q10 for 2pi(b) in control and actin filament
      reconstituted myocardium was 3.8 and 4.0, respectively. There were two phases to
      the temperature dependence of 2pi(c) (rate constant of quick recovery). In
      control and thin filament-reconstituted myocardium, Q10 for 2pi(c) was
      approximately 5.5 in the low temperature range (< or = 25 degrees C) and 2.7 in
      the high temperature range (> or = 30 degrees C). In actin filament-reconstituted
      myocardium, Q10 for 2pi(c) was 8.5 in the low temperature range and 3.6 in the
      high temperature range. The above results demonstrate that regulatory proteins
      augment the temperature dependence of isometric tension, indicating that the
      regulatory proteins may modify the actomyosin interaction.

PMID- 11850519
TI  - Measurement of interstitial lactate during hypoxia-induced dilatation in isolated
      pressurised porcine coronary arteries.
AB  - Lactate is formed in the coronary arterial wall and in the myocardium as a
      consequence of ischaemia and infarction. We combined direct measurement of
      coronary artery diameter and interstitial arterial wall lactate concentration ex
      vivo in order to ascertain the possible role of lactate in hypoxia-induced
      vasodilatation. The wall of porcine coronary arteries, precontracted during an
      intraluminal pressure of 40 mmHg by addition of prostaglandin F2alpha, was
      cannulated using a microdialysis catheter, and exposed to hypoxia for 60 min,
      followed by 45 min of reoxygenation. The exchange fraction of [14C]lactate over
      the microdialysis membrane increased from 0.38 +/- 0.04 to 0.52 +/- 0.05 (P <
      0.001) during the study period. Coronary artery diameter increased by 15.5 +/-
      2.0 % (n = 20) during hypoxia (P < 0.001, compared to normoxic controls) and
      interstitial lactate concentration rose from 1.07 +/- 0.21 to 2.50 +/- 0.40 mmol
      x l(-1) during hypoxia (P < 0.01) and was unchanged in controls. The increase in
      coronary artery diameter correlated with the increase in interstitial lactate
      concentration in the period between 30 and 60 min of hypoxia (r = 0.62; P =
      0.02). Dichloroacetate (10(-5) M), an agent that reduces lactate generation by
      activating pyruvate dehydrogenase, abolished hypoxia-induced lactate production,
      but caused a further increase in coronary arterial diameter (30.2 +/- 4.4 %, n =
      9; P < 0.001 vs. hypoxia and no dichloroacetate). Under control conditions, the
      addition of L-lactate (10(-3)-10(-2) M) increased dose-dependently coronary
      arterial diameter by 22.0 +/- 4.2 % (n = 5) and interstitial lactate
      concentration from 0.52 +/- 0.04 to 5.70 +/- 0.66 mmol x l(-1) (P < 0.001). There
      was a correlation between the increase in coronary artery diameter and
      interstitial lactate concentration (r = 0.60; P = 0.02). The present observations
      represent the first direct measurements of metabolites by microdialysis in a
      blood vessel wall. The lactate concentration may affect, but is not essential
      for, hypoxia-induced vasodilatation in porcine coronary arteries.

PMID- 11850520
TI  - Openings in frog microvascular endothelium at different rates of increase in
      pressure and at different temperatures.
AB  - Experiments were carried out on single mesenteric capillaries and venules of
      pithed frogs to determine whether the rate of increase in intravascular pressure
      (dP/dt) influenced the critical pressure (P(B)) which increases wall
      permeability. Vessels, microperfused with frog Ringer solutions containing 0.1%
      bovine serum albumin and red cells, were occluded downstream before pressure was
      raised either as a ramp or in a series of 13.6 cmH2O steps. By varying step
      duration, the mean dP/dt could be matched to dP/dt applied as a steady ramp. P(B)
      was recorded as the pressure at which there was an abrupt increase in filtration
      with red cells passing to and through one or more sites in the vessel wall. In
      all vessels, increasing dP/dt raised P(B), with no differences between steps and
      ramps. The relation between P(B) and dP/dt was linear, consistent with a latent
      period, T (the slope), between a critical pressure being reached and the abrupt
      increase in permeability being observed. Direct observation confirmed this latent
      period. Between 12 and 20 (o)C, T was 8.5 +/- 0.47 s; between 0 and 5 degrees C,
      T was 11.5 +/- 0.97 s. Tissue cooling did not influence the time constant, tau,
      describing the rate of stretch of wall following a step increase in pressure and
      used to measure wall visco-elastic properties. Nor was the value of tau (1.15 +/-
      0.06 s, n = 42) consistent with T being accounted for by visco-elasticity. It is
      suggested that the latent period may indicate an active response of the
      endothelium.

PMID- 11850521
TI  - Rho and rho kinase modulation of barrier properties: cultured endothelial cells
      and intact microvessels of rats and mice.
AB  - Previous experiments using cultured endothelial monolayers indicate that Rho
      family small GTPases are involved in modulation of endothelial monolayer
      permeability by regulating assembly of the cellular actin filament scaffold,
      activity of myosin-based contractility and junctional distribution of the Ca2+
      dependent endothelial cell adhesion molecule, VE-cadherin. We investigated these
      mechanisms using both cultured endothelial cells (from porcine pulmonary artery
      and mouse heart) and vascular endothelium in situ (mouse aorta, and individually
      perfused venular microvessels of mouse and rat mesentery). Exposure to
      Clostridium difficile toxin B (100 ng x ml(-1)) inactivated 50-90% of all
      endothelial Rho proteins within 60-90 min. This was accompanied by considerable
      reduction of actin filament stress fibres and junctional F-actin in cultured
      endothelial monolayers and in mouse aortic endothelium in situ. Also, VE-cadherin
      became discontinuous along endothelial junctions. Inhibition of Rho kinase with Y
      27632 (30 microM) for 90-120 min induced F-actin reduction both in vitro and in
      situ but did not cause redistribution or reduction of VE-cadherin staining.
      Perfusion of microvessels with toxin B increased basal hydraulic permeability
      (L(p)) but did not attenuate the transient increase in L(p) of microvessels
      exposed to bradykinin. Perfusion of microvessels with Y-27632 (30 microM) for up
      to 100 min reduced basal L(p) but did not attenuate the permeability increase
      induced by platelet activating factor (PAF) or bradykinin. These results show
      that toxin B-mediated reduction of endothelial barrier properties is due to
      inactivation of small GTPases other than RhoA. Rho proteins as well as RhoA
      mediated contractile mechanisms are not involved in bradykinin- or PAF-induced
      hyperpermeability of intact microvessels.

PMID- 11850522
TI  - Mutant mice deficient in NOS-1 exhibit attenuated long-term facilitation and
      short-term potentiation in breathing.
AB  - The objective of the present study is to examine the potential role of nitric
      oxide (NO) in short-term potentiation (STP) and long-term facilitation (LTF) of
      breathing. Experiments were performed in wild-type (WT) and mutant mice deficient
      in nitric oxide synthase-1 (NOS-1), as well as in WT mice administered the NOS-1
      inhibitor 7-nitroindazole (7-NI; 50 mg x kg(-1); I.P.). Respiratory responses
      following either single or recurrent episodes of hypoxia (7% O2, balance N2) were
      analysed in unanaesthetised animals by body plethysmography along with rate of O2
      consumption (VO2)) and CO2 production (VCO2). After a single hypoxic challenge,
      respiration in WT mice remained elevated for 5 min, suggesting STP in
      ventilation. Following termination of three consecutive hypoxic challenges,
      respiration remained elevated during normoxia for as long as 30 min, indicating
      LTF in breathing under awake conditions. STP and LTF were significantly
      attenuated or absent in WT mice after 7-NI. A similar attenuation or absence of
      STP and LTF was also seen in NOS-1 mutant mice. Changes in VO2 and VCO2 were
      comparable among mice during the post-hypoxic period, suggesting that the absence
      of STP and LTF was not due to alterations in body metabolism. These results
      suggest endogenous NO is an important physiological modulator of ventilatory STP
      and LTF.

PMID- 11850525
TI  - Isolated noncompaction of the ventricular myocardium: clinical and molecular
      aspects of a rare cardiomyopathy.

PMID- 11850523
TI  - Anticipatory control of hand and eye movements in humans during oculo-manual
      tracking.
AB  - Anticipatory activity of hand and eye has been examined during oculo-manual
      tracking of a constant velocity visual target with a hand cursor. Both target and
      cursor were presented briefly (< 480 ms), but repeatedly, at regular inter
      stimulus intervals (ISI). In Expt 1, the build-up of hand and eye responses was
      examined for target velocities varying from 10-40 deg x s(-1) with an ISI of 2.4
      s. The velocity 100 ms after target onset (i.e. prior to visual feedback) for
      both hand and eye (V100) progressively increased over the first four
      presentations but then attained a steady state (SS). SS V100 values for eye and
      hand increased in proportion to target velocity and were thus predictive of
      forthcoming movement. Hand velocity exceeded eye velocity but both exhibited
      similar anticipatory trajectories. In Expt 2, target velocity was constant (40
      deg x s(-1)) but ISI varied from 0.48-3.74 s. Subjects made anticipatory eye
      movements for all ISIs but hand movements were often reactive at the longest ISI.
      If the target failed to appear as expected, subjects initiated predictive hand
      and eye responses with timing appropriate for the prevailing ISI. In Expt 3,
      predictive responses were compared with responses to randomised presentation.
      Peak hand velocity was greater in the randomised mode than in the predictive
      condition, whereas the converse was true for peak eye velocity. This difference
      is discussed in terms of the mechanisms of positional error correction in hand
      and eye. Results provide evidence of similar anticipatory mechanisms in hand and
      eye, using storage of velocity and timing to achieve rapid prediction of target
      motion.

PMID- 11850526
TI  - p16(INK4a) is selectively silenced in the tumoral progression of mycosis
      fungoides.
AB  - Knowledge about the molecular mechanisms involved in the pathogenesis of tumoral
      progression in mycosis fungoides (MF) is still scarce. Because the 9p21 locus
      seems to be a good target for a detailed study in MF, this prompted us to compare
      the mechanisms of inactivation of the p16(INK4a), p15(INK4b), and p14(ARF) genes
      in aggressive and stable forms of MF, performing microsatellite analysis,
      methylation-specific polymerase chain reaction, direct sequencing, and p16(INK4a)
      protein expression by immunohistochemistry. Additionally, the p53 gene was also
      sequenced in tumoral lesions. Thirty-nine patients with stable MF were studied.
      Alterations in p16(INK4a) and p15(INK4b) genes were detected in 18% and 5% of the
      cases, respectively. None of the cases analyzed showed alterations of the
      p14(ARF) gene. In contrast with these findings, in the 11 patients with
      aggressive MF, alterations of the p16(INK4a), p15(INK4b), or p14(ARF) genes were
      found in 8 (73%), 3 (27%), and 2 (18%) cases, respectively. A significant
      proportion (4/11) of these alterations were already present in the p16(INK4a)
      gene in the initial plaque lesions in these aggressive forms of MF. Alterations
      in the p16(INK4a) gene, either methylation or loss of heterozygosity, were
      clearly more frequent than those in the p15(INK4b) and p14(ARF) genes. These
      p16(INK4A) alterations were confirmed using immunohistochemistry. None of the
      nine tumoral lesions analyzed showed mutations in exons 1-2 of the p16(INK4a)
      gene or in exons 5-8 of the p53 gene. These results seem to suggest that 9p21
      alterations, and selectively p16(INK4a) silencing, could be a characteristic
      phenomenon in MF progression.

PMID- 11850527
TI  - Neutrophil proteinases in hydrochloric acid- and endotoxin-induced acute lung
      injury: evaluation of interstitial protease activity by in situ zymography.
AB  - We investigated the role of polymorphonuclear neutrophil (PMN) proteinases,
      elastase, and gelatinase B in rat models of acute lung injury. Three groups of
      rats were studied 6 hours after unilateral instillation of hydrochloric acid
      (HCl; 0.1 N), lipopolysaccharide (LPS) (4 microg), or saline. The results
      demonstrated that HCl-induced lung injury, as compared with LPS-induced lung
      injury, was associated with an increase in permeability (wet/dry weight ratio and
      proteins in bronchoalveolar lavage fluid). In contrast, there was similar PMN
      recruitment (in bronchoalveolar lavage fluid and myeloperoxidase activity in lung
      homogenates) and similar proteinase exocytosis (residual alveolar PMN content of
      elastase and gelatinase B) in both types of lung injury. In situ zymography,
      evaluating interstitial protease/inhibitor balance, demonstrated a decrease in
      gelatinolytic activity in both HCl- and LPS-injured lungs compared with normal
      lung. The increase in interleukin 6 concentration in lung homogenates, which is
      observed after both injuries compared with saline-instilled animals, could be
      involved in up-regulation of tissue inhibitor of matrix metalloproteinase-1,
      shown by immunocytochemistry to participate in antiproteinase excess. Neither
      inhibition of alveolar neutrophil influx using a leukocyte elastase inhibitor
      (EPI-hNE-4) nor inhibition of gelatinase activities by recombinant adenovirus for
      the human tissue inhibitor of matrix metalloproteinase 1 gene transfer decreased
      lung edema in HCl-induced injury. These data suggest that PMN proteinases do not
      contribute to HCl-induced acute lung injury in rats.

PMID- 11850528
TI  - Galectin-1 is overexpressed in nasal polyps under budesonide and inhibits
      eosinophil migration.
AB  - Because of the importance of galectins for various cellular activities, the
      influence of the glucocorticoid budesonide on the level of expression of
      galectins-1 and -3 was investigated in human nasal polyposis. Ten nasal polyps
      obtained from surgical resection were maintained for 24 hours in the presence of
      various concentrations of budesonide. As quantitatively demonstrated by means of
      computer-assisted microscopy, 250 ng/ml (the highest dose tested) induced a
      pronounced increase of galectin-1 expression. This feature was observed in nasal
      polyps from allergic patients but not in those from nonallergic patients. Since
      eosinophils represent the main inflammatory cell population in nasal polyps, we
      investigated the effect of galectin-1 on their migration levels by means of
      quantitative phase-contrast computer-assisted videomicroscopy. Our results show
      that galectin-1 (coated on plastic supports) markedly reduced the migration
      levels of eosinophils in comparison to P-selectin. On the cellular level, marked
      modifications in the polymerization/depolymerization dynamics of the actin
      cytoskeleton (as revealed by means of computer-assisted fluorescence microscopy)
      and, to a much lesser extent, an increase in the adhesiveness of eosinophils to
      tested substrata were detectable. The present study therefore reveals a new
      galectin-1-mediated mechanism of action for glucocorticoid-mediated anti
      inflammatory effects.

PMID- 11850529
TI  - VASA is a specific marker for both normal and malignant human germ cells.
AB  - VASA is so far the only known gene in mammals whose expression is specific for
      the germ cell lineage. We investigated the presence of VASA mRNA and protein in a
      series of germ cell tumors of different histologic subtypes and anatomic
      location, as well as in nongerm cell tumors such as testicular lymphomas and
      Leydig cell tumors. We detected VASA mRNA (by quantitative RT-PCR) and protein
      (by immunohistochemical staining) in normal spermatogenesis, seminoma (both
      classic and spermatocytic), carcinoma in situ (the precursor of classic seminoma
      and nonseminoma), dysgerminoma, and gonadoblastoma. VASA immunostaining was
      relatively weak in seminomas and dysgerminomas compared with spermatocytic
      seminomas, despite similar mRNA levels, suggesting that VASA is regulated in part
      by post-transcriptional mechanisms. A higher staining intensity compared with the
      invasive counterparts was observed in the precursor lesions (ie, carcinoma in
      situ and gonadoblastoma). No VASA mRNA or protein was detectable in
      nonseminomatous germ cell tumors (such as embryonal carcinoma, teratoma, and yolk
      sac tumor) and derived cell lines, or nongerm cell tumors such as lymphoma or
      Leydig cell tumor. These results provide direct evidence that some germ cell
      tumors retain germ cell characteristics, whereas other tumors of germ cell origin
      result from differentiation and loss of germ cell identity. Furthermore, these
      findings suggest that VASA is likely to serve as a useful and highly specific
      biomarker for germ cell tumors, particularly classic and spermatocytic
      seminoma/dysgerminoma, including their precursor stages.

PMID- 11850530
TI  - Preclinical evaluation of a phosphorothioate oligonucleotide in the retina of
      rhesus monkey.
AB  - Overexpression of vascular endothelial growth factor (VEGF) has been strongly
      implicated in the development of choroidal neovascularization (CNV) in patients
      with age-related macular degeneration. In this study, a phosphorothioate
      oligonucleotide (PS-oligo) targeting both human and rat VEGF(165) genes upstream
      of the translation initiation code, named DS135 in this study, was evaluated for
      its uptake dynamics and retinal tolerance after intravitreal (IV) and subretinal
      (SR) injections in the rhesus monkey. Intravitreal and SR injections of a
      fluorescent-labeled DS135 (FL-DS135) resulted in both dose- and time-dependent
      uptake and persistence, and FL-DS135 remained detectable in the retina for at
      least 3 weeks after injection. Ophthalmic examination showed transient vitreous
      haze after IV delivery of a high dose but not with a low dose of FL-DS135.
      Histologic examination showed no evidence of retinal degeneration with respect to
      IV delivery. After SR delivery, however, dose-related cellular infiltration,
      transient residual fluid, and slight distortion of the neuroretina were observed.
      The biologic efficacy of DS135 was further assessed in a laser-induced CNV model,
      and development of CNV was determined by fluorescein angiography and histologic
      examination. Incomplete inhibition of CNV formation was observed after IV and SR
      injection of DS135, but no statistically significant difference was achieved when
      compared with dose-matched control of PS-oligo. Analysis of fluorescein angiogram
      and histologic examination showed less than 30% incidence of CNV development in
      this monkey model. Our study demonstrated that PS-oligos can be successfully
      introduced into the retina, although with potential limitations, after SR
      delivery. DS135, a PS-oligo targeting the VEGF gene upstream of the translation
      initiation code, partially inhibited CNV formation. An improved CNV model is
      necessary for further confirmation of the full therapeutic potency of DS135
      before clinical application.

PMID- 11850532
TI  - Tissue distribution and induction of human multidrug resistant protein 3.
AB  - The multidrug resistance protein (MRP) family consists of several members and,
      for some of these transporter proteins, distinct roles in multidrug resistance
      and normal tissue functions have been well established (MRP1 and MRP2) or are
      still under investigation (MRP3). MRP3 expression studies in human tissues have
      been largely restricted to the mRNA level. In this report we extended these
      studies and further explored MRP3 expression at the protein level. Western blot
      and immunohistochemistry with two MRP3-specific monoclonal antibodies, M(3)II-9
      and M(3)II-21, showed MRP3 protein to be present in adrenal gland, and kidney and
      in tissues of the intestinal tract: colon, pancreas, gallbladder, and liver. In
      epithelia, MRP3 was found to be located at the basolateral sides of cell
      membranes. In normal liver, MRP3 was detected at lower levels than anticipated
      from the mRNA data and was found present mainly in the bile ducts. In livers from
      patients with various forms of cholestasis, MRP3 levels were frequently increased
      in the proliferative cholangiocytes, with sometimes additional staining of the
      basolateral membranes of the hepatocytes. This was especially evident in patients
      with type 3 progressive familial intrahepatic cholestasis. The present results
      support the view that MRP3 plays a role in the cholehepatic and enterohepatic
      circulation of bile and in protection within the biliary tree and tissues along
      the bile circulation route against toxic bile constituents. The possible
      functional roles for MRP3 in the adrenal gland and in the kidney remain as yet
      unknown. In a panel of 34 tumor samples of various histogenetic origins, distinct
      amounts of MRP3 were detected in a limited number of cases, including lung,
      ovarian, and pancreatic cancers. These findings may be of potential clinical
      relevance when considering the drug treatment regimens for these tumor types.

PMID- 11850533
TI  - Up-regulation of M3-muscarinic receptors in labial salivary gland acini in
      primary Sjogren's syndrome.
AB  - M3-muscarinic receptors (M3R) mediate parasympathetic cholinergic
      neurotransmission to salivary and lacrimal glands, and autoantibodies to these
      receptors have been implicated in sicca symptoms and autonomic dysfunction in
      Sjogren's syndrome. We have investigated the expression of M3R in paraffin
      embedded labial salivary glands (LSG) from seven patients with primary Sjogren's
      syndrome (pSS) and five healthy controls using high-resolution confocal
      microscopy and an affinity-purified goat polyclonal antibody raised against the
      COOH-terminal sequence of the human M3R. Immunolocalization of M3R was similar in
      control and pSS glands, with punctate staining of M3R in the basal membrane of
      acinar cells and in the luminal and abluminal membrane of myoepithelial cells.
      Bright, granular M3R staining was also detected in the cytoplasm and membranes of
      all intercalated and striated ducts, and infiltrating lymphocytes in pSS. All
      immunoreactivity was specifically blocked by the immunizing peptide. An increase
      in M3R expression specifically in acini in pSS was demonstrated by a 30% increase
      in receptor number per cluster and a 68% increase in the number of clusters in
      the membrane. This up-regulation is consistent with inhibition of parasympathetic
      neurotransmission, possibly by antagonistic autoantibodies to M3R. The up
      regulation, rather than down-regulation, of M3R in acini of pSS LSG can explain
      the effectiveness of muscarinic agonists in treating sicca symptoms in pSS.

PMID- 11850531
TI  - Constitutive expression and regulation of rat complement factor H in primary
      cultures of hepatocytes, Kupffer cells, and two hepatoma cell lines.
AB  - The 155-kd soluble complement regulator factor H (FH), which consists of 20 short
      consensus repeats, increases the affinity of complement factor I (FI) for C3b by
      about 15 times. In addition to its cofactor activity, it prevents factor B from
      binding to C3b and promotes the dissociation of the C3bBb complex. The primary
      site of synthesis of FH, as well as of FI, is the liver, but the cell types
      responsible for the hepatic synthesis of both factors have not yet been clearly
      identified. In contrast to FI-mRNA, which was detectable only in hepatocytes
      (HC), FH-specific mRNA was identified in both HC and Kupffer cells (KC). As
      calculated for equal amounts of mRNA isolated from both cell types, FH-specific
      mRNA was found to be nearly 10-fold higher in KC than in HC, leading to the
      conclusion that KC are an abundant source of FH. Of the investigated
      proinflammatory cytokines IL-6, TNF-alpha, IL-1beta, and IFN-gamma, only IFN
      gamma up-regulated FH-specific mRNA up to 6-fold in both primary HC and KC. This
      was also demonstrable on the protein level. However, FH-specific mRNA was not
      inducible in the rat hepatoma cell line H4IIE, which did not express FH-specific
      mRNA and could not be up-regulated in FAO cells that constitutively expressed FH
      specific mRNA. This demonstrates that transformed cell lines do not reflect FH
      regulation in isolated primary HC. In addition to IFN-gamma, the endotoxin
      lipopolysaccharide (LPS) up-regulated FH-specific mRNA nearly 10-fold in KC after
      stimulation at concentrations of 10 or 1 ng/ml. In contrast, concentrations of up
      to 2 microg LPS/ml did not show any effect on HC. Our data suggest that LPS does
      not regulate the expression of FH in HC.

PMID- 11850534
TI  - Investigation of a mechanism for accelerated breakdown of immune tolerance to the
      primary biliary cirrhosis-associated autoantigen, pyruvate dehydrogenase complex.
AB  - Primary biliary cirrhosis (PBC) is an autoimmune liver disease characterized by
      autoreactive T- and B-cell responses to the highly conserved enzyme pyruvate
      dehydrogenase complex (PDC). In this study we have examined the breakdown of T
      cell tolerance to self-PDC using a mouse model. Female SJL/J mice were sensitized
      intraperitoneally with foreign-PDC (bovine) and/or self-PDC (murine) in complete
      Freund's adjuvant, and serum, spleen, and liver tissue was taken 8 weeks later.
      Animals sensitized with foreign-PDC produced IgG antibodies that were reactive
      with both foreign and self-PDC, but splenic T cells from these animals only
      responded to stimulation with foreign PDC. Sensitization with self-PDC elicited
      neither antibodies nor reactive T cells. Significantly, cosensitization with
      mixed self-PDC and foreign-PDC resulted in a full breakdown of self-tolerance,
      with generation of both antibody and T-cell responses to self-PDC of the type
      seen exclusively in human PBC patients. Mild bile duct lesions deficient in
      CD8(+) T cells were seen 8 weeks after sensitization with either foreign or self
      PDC. However, after sensitization with mixed self-PDC and foreign-PDC, these
      lesions were significantly larger and heavily infiltrated by CD8(+) T cells.
      Liver-infiltrating T cells derived from the self-PDC and foreign-PDC cosensitized
      but not from control animals showed reactivity with self-PDC, suggesting a
      possible role for autoreactive PDC-specific T-cell responses in the pathogenesis
      of the observed histologic changes. It is likely that B-cell cross-reactivity
      between foreign and self-PDC enhances the potential for breakdown of T-cell self
      tolerance by allowing efficient presentation of self-antigens in the inoculum.
      This model may provide a useful system for investigating the etiology and
      treatment of PBC.

PMID- 11850535
TI  - Activation of trkA induces differentiation and inhibits the growth of JK-GMS
      Askin tumor cells.
AB  - Peripheral primitive neuroectodermal tumor (PNET) and Ewing's sarcoma (ES)
      constitute a unique group of small round cell tumors in childhood and young
      adults that are characterized by the same chromosomal translocation
      t(11;22)(q24;q12). Recently, the expression of neurotrophin receptors has been
      found in various human tumors including PNET/ES, but the functional significance
      of these receptor expressions has not been documented in PNET/ES. In the present
      study, we investigated the biologic effects of trkA neurotrophin receptor
      activation by nerve growth factor (NGF) in a newly established Askin tumor cell
      line, JK-GMS, which constitutively expresses a high level of trkA. The activation
      of trkA induced differentiation and inhibited the growth of JK-GMS cells, which
      was characteristically associated with down-regulation of c-myc and N-myc mRNA
      expression. NGF did not exert significant changes in two different PNET/ES cell
      lines, CADO-ES1 and RD-ES, which did not express detectable levels of trkA. The
      biologic effects mediated by NGF were abrogated by treatment of the cells with K
      252a, and the treatment with brain-derived neurotrophic factor did not affect the
      biologic behavior of JK-GMS cells, indicating that the effects are trkA specific.
      The results observed were quite similar to those of neuroblastoma cells, another
      childhood tumor of neural crest origin. Overall findings strongly suggest that
      the trkA-mediated signaling pathway plays a crucial role in controlling the basic
      biologic properties of JK-GMS cells.

PMID- 11850536
TI  - Rho GTPase inactivation impairs lens growth and integrity.
AB  - To elucidate the significance of Rho GTPase signaling on lens growth and
      structural integrity, we have selectively inactivated Rho GTPase in the ocular
      lens. To achieve this tissue-specific inactivation, a transgene encoding the C3
      exoenzyme from Clostridium botulinum has been expressed in mice under
      transcriptional control of the lens-specific alphaA-crystallin promoter. C3
      exoenzyme is known to selectively inactivate all Rho GTPase isoforms by ADP
      ribosylating an asparagine residue at position 41. Mice expressing the C3
      exoenzyme transgene exhibited selective ocular defects, including cataract and
      microphthalmia. Extralenticular effects included ocular hemorrhage (blood
      accumulation in the anterior and posterior chambers of the eye) and abnormalities
      of the iris including focal attachments to lens and cornea (synechiae). C3
      transgene expression was found only in the lens and not in the other ocular
      tissues as determined by RT-PCR analysis. Histologic examination of the eyes of
      C3 transgenic mice from two independent lines revealed extensive abnormalities of
      the lens, including defective fiber cell differentiation and elongation, ruptured
      posterior lens capsule, and thickened anterior lens capsule. Electron microscopic
      analysis of hemorrhaged C3 eyes showed abnormalities in the posterior hyaloid
      vessels. Collectively these data reveal the importance of Rho GTPase signaling in
      regulating lens growth and maintenance of lens transparency.

PMID- 11850537
TI  - Histologic and radiographic analysis of ductal carcinoma in situ diagnosed using
      stereotactic incisional core breast biopsy.
AB  - BACKGROUND: Stereotactic incisional core breast biopsy (SCBB) is a highly
      specific technique for diagnosing ductal carcinoma in situ (DCIS) in patients
      with suspicious mammographic microcalcifications. However, its sensitivity for
      excluding the presence of coexisting occult invasive disease in this setting is
      not fully established. DESIGN: We correlated SCBB findings to subsequent
      lumpectomy/mastectomy (lx/mx) results in 122 cases of DCIS. In 29 of these cases,
      the SCBB showed microscopic invasion (n = 15) or foci that were suspicious for
      invasion (n = 14). Likelihood for invasive disease in subsequent lx/mx samples
      from each case then was compared with various parameters, including DCIS grade,
      extent and mammographic findings. RESULTS: Overall, 13% of cases in which the
      SCBB showed DCIS only (i.e., without any evidence of invasion), had invasive
      disease in the subsequent excision. This finding was significantly correlated
      with DCIS grade (low: 0/26 [0%], intermediate: 2/31 [6%], high: 10/36 [28%], P
      <.001). Invasive lesions were usually small (nine T1a, one T1b, and two T1c) and
      typically present within more extensive fields of DCIS (no invasion: 1.5 cm DCIS
      size; invasion: 2.8 cm mean DCIS size, P =.01). This was reflected by greater
      extent of involvement in the SCBB (5/8 cases with invasion had >15 ducts
      involved, versus 4/23 with <15 ducts involved, P =.03). SCBB that were suspicious
      or positive for microinvasion demonstrated invasion in most subsequent excision
      (susp: 7/14 [50%], microinv: 11/15 [73%]), generally of significant extent (11/18
      T(1b-c)). CONCLUSIONS: 1. Patients with SCBB showing high grade DCIS and DCIS
      suspicious or positive for microinvasion have a significant and high likelihood,
      respectively, of harboring occult invasive neoplasm. They should accordingly be
      carefully evaluated radiographically, and possibly with sentinel node biopsy to
      facilitate axillary staging. 2. Likelihood of occult invasion is correlated with
      overall DCIS size/extent.

PMID- 11850538
TI  - Autoimmune gastritis: distinct histological and immunohistochemical findings
      before complete loss of oxyntic glands.
AB  - Autoimmune gastritis (AG) can be easily recognized when the histological features
      are fully developed, but recognizing AG before the complete loss of the oxyntic
      mucosa is more challenging. One feature of fully developed AG is enterochromaffin
      cell-like (ECL) hyperplasia, but its presence or absence in earlier stages of AG
      has not been fully evaluated. A retrospective study of biopsy specimens from 40
      patients was performed; all of the patients were originally diagnosed with
      possible AG based on the presence of lymphocytic infiltration and damage to
      oxyntic glands and/or the presence of metaplastic epithelium that
      disproportionately involved the body mucosa. Nineteen cases had follow-up
      serological studies for anti-parietal cells and/or anti-intrinsic factor
      antibodies: 13 were positive and 6 negative. The remaining 21 cases were
      indeterminate because of incomplete testing. The histological findings were
      similar in the patients who were serologically positive and those who were
      indeterminate for AG. In all of these cases, the oxyntic mucosa showed
      lymphoplasmacytic infiltrates within the lamina propria with focal gland
      infiltration and damage. Sixty-five percent (22/34) of the cases showed
      intestinal and/or pyloric metaplasia, and 85% (29/34) showed parietal cell
      pseudohypertrophy. Chromogranin stains were performed in 11 of 13 cases with
      positive serological markers for AG, and all showed at least linear ECL cell
      hyperplasia. In contrast, none of the six cases with negative serological studies
      had linear ECL cell hyperplasia, P <.001. In conclusion, the following
      constellation of findings supports a diagnosis of AG before the complete loss of
      oxyntic mucosa: deep or diffuse lymphoplasmacytic infiltrates within the lamina
      propria with foci of gland infiltration and damage, epithelial metaplasia,
      parietal cell pseudohypertrophy, and ECL cell hyperplasia at the linear or
      greater level.

PMID- 11850539
TI  - Immunohistochemical detection of hepatocellular carcinoma in the setting of
      ongoing necrosis after radiofrequency ablation.
AB  - After radiofrequency ablation (RFA), hepatocellular carcinoma undergoes complete
      necrosis and an ongoing necrosis that is irreversible and characterized
      histologically by disrupted cell outlines, homogenous cytoplasmic eosinophilia,
      and preserved nuclear staining, with the cells appearing quite distinct from
      viable cancer cells. Antibody to detect single-stranded DNA (ssDNA) specifically
      labeled nuclei in the setting of ongoing necrosis, but not viable tumor cells,
      whereas human mitochondrial antibody labeled the cytoplasm of viable cells but
      not cells of ongoing necrosis. The results demonstrate that RFA causes
      denaturation of both DNA and proteins and that the immunohistochemistry of ssDNA
      and mitochondrial protein is useful in detection of ongoing necrosis after RFA
      and provides pathological information on the validity of this procedure.

PMID- 11850540
TI  - Amplification of Her-2/neu gene in Her-2/neu-overexpressing and -nonexpressing
      breast carcinomas and their synchronous benign, premalignant, and metastatic
      lesions detected by FISH in archival material.
AB  - Amplification of Her-2/neu in breast carcinoma is associated with poor prognosis,
      short disease-free interval, and short survival time in both node-negative and 
      positive patients. Little is known about the starting point of amplification of
      Her-2/neu and how it progresses from benign to malignant breast lesions. We
      attempted to address these questions by evaluating amplification of Her-2/neu in
      benign, premalignant, and malignant lesions using fluorescence in situ
      hybridization (FISH). Twenty-six patients with Her-2/neu-overexpressing invasive
      ductal carcinomas (as judged by strong immunoreactivity with Her-2/neu antibody)
      and coexisting lesions of ductal hyperplasia (DH), atypical ductal hyperplasia
      (ADH), ductal carcinoma in situ (DCIS) in the vicinity of the invasive tumor (as
      judged by review of the hematoxylin and eosin-stained sections), as well as
      metastatic carcinoma in axillary lymph nodes (mets) were selected for this study.
      In the primary carcinomas, a close relationship was present between
      overexpression as detected by immunohistochemistry (IHC) and amplification as
      demonstrated by FISH (85% concordance). Among these patients, amplification of
      Her-2/neu in ADH was demonstrated in 7 of 13 cases with ADH, and in DCIS, in 21
      of 22 cases with DCIS. There was no amplification in DH or normal ductal
      epithelium. Significantly, in all 12 patients with synchronous positive axillary
      lymph nodes, there was concordant amplification of Her-2/neu in the primary and
      metastatic carcinoma. Amplification was consistent in multifocal metastases,
      despite morphological heterogeneity in some patients. Amplification ratios
      increased from ADH to DCIS to invasive carcinoma (P <.01, ADH versus DCIS; P
      <.05, DCIS versus invasive cancer), but there was no difference in amplification
      ratios between primary cancers and synchronous axillary metastases (P >.05). We
      also evaluated Her-2/neu amplification in 21 patients without Her-2/neu
      overexpression in their primary carcinomas (as judged by absent immunoreactivity
      with Her-2/neu antibody). Three showed amplification in both primary and
      metastatic lesions, with a low amplification ratio (approximately 2). One patient
      had amplification in the primary tumor but not in an axillary metastasis. Two
      patients exhibited slight amplification in the metastatic carcinoma (ratios 1.6
      and 2), but not in their primary cancers. This FISH study indicates that
      amplification of Her-2/neu can emerge de novo in any stage of the disease
      process, from ADH to metastatic lesions, but most often appears first in ADH or
      DCIS. The degree of Her-2/neu amplification increases with progression to
      invasive carcinoma, there being no further increase in synchronous metastasis.
      Our data suggest that amplification of Her-2/neu appears to be mainly involved in
      initiation of breast oncogenesis and that its role in progression of breast
      cancers is uncertain.

PMID- 11850541
TI  - c-kit mutations in gastrointestinal stromal tumors occur preferentially in the
      spindle rather than in the epithelioid cell variant.
AB  - Gastrointestinal stromal tumors (GISTs) coexpress CD34 and the Kit tyrosine
      kinase receptor (CD117). A subset of GISTs carry gain-of-function mutations of
      the c-kit proto-oncogene in its juxtamembrane domain. The relationship between
      the mutational status and histological as well as immunohistochemical features
      has not been assessed in detail. 36 GISTs and 14 other gastrointestinal
      mesenchymal tumors were investigated for their morphology and immunophenotype as
      well as for the presence of c-kit mutations. DNA was extracted from formalin
      fixed, paraffin-embedded tissue. Exons 9, 11, 13, and 17 of c-kit were analyzed
      by SSCP. Bands with altered mobility were excised, reamplified, and sequenced. C
      kit mutations in Exon 11 encoding the juxtamembrane domain were identified in 19
      cases (52.8%), with deletions in 12 cases, insertions in 3 cases (2 of these as
      duplications), and point mutations in 4 cases. The mutations clustered between
      Codons 553 and 561, pinpointing the critical region for deregulated Kit receptor
      activation. In both Exons 9 and 13, single mutations could be identified, whereas
      no mutations were found in Exon 17. There were c-kit mutations in 66.6% of benign
      GISTs (14/21), 83.3% of the malignant (5/6), and 40% of the cases of intermediate
      malignancy (2/5). A low frequency of mutations in benign GISTs, as reported
      previously by other researchers, could not be observed in our panel.
      Interestingly, all GISTs with c-kit mutations displayed a spindle cell phenotype,
      whereas mutations were absent in all 7 tumors with an epithelioid component (P
      =.03). This finding suggests a relationship between c-kit mutation and
      histological subtype in GISTs.

PMID- 11850542
TI  - Aneusomy 17 in breast cancer: its role in HER-2/neu protein expression and
      implication for clinical assessment of HER-2/neu status.
AB  - HER-2/neu protein overexpression in breast cancer is mostly caused by HER-2/neu
      gene amplification. However, it is unclear whether aneusomy 17 may also play a
      role. Using immunohistochemistry assay (IHC) with DAKO antibody and manual
      quantitation, 189 specimens were selected from archival invasive breast cancer
      specimens, including most IHC-positive and some IHC-negative cases (n = 158 and
      31, respectively). They were then analyzed by PathVysion fluorescence in situ
      hybridization (FISH) assay (Vysis, Inc., Downers Grove, IL) and by an image
      analyzer (ACIS; ChromaVision Medical Systems, Inc., San Juan Capistrano, CA)
      assisted IHC quantitation. Ninety-two cases contained disomy 17 (chromosome 17
      centromere, 1.76-2.25 signals per cell) whereas 97 cases had aneusomy 17,
      including 82 with low polysomy (2.26-3.75 signals per cell), 10 with high
      polysomy (> or =3.76 signals per cell), and 5 with hypodisomy (> or =1.75 signals
      per cell). HER-2/neu protein expression had the highest correlation with HER
      2/neu gene dosage (copy number; r =.826), followed by the HER-2/neu gene to
      chromosome 17 ratio (r =.733). The lowest correlation was with the chromosome 17
      copy number (r =.307), on which the 10 cases with high polysomy 17 had a
      disproportionately high impact. The FISH assay using the PathVysion criterion for
      HER-2/neu gene amplification (HER-2/neu gene to chromosome 17 ratio, > or = 2.00)
      achieved higher concordance with ACIS IHC than did an alternative FISH criterion
      (absolute HER-2/neu gene copy number, > or = 4.00 signals per cell). Most ACIS
      IHC-PathVysion FISH-discordant cases contained disomy or low polysomy 17, whereas
      all 10 cases with high polysomy 17 had no such discordance. However, two cases
      with monosomy 17 had ACIS IHC-PathVysion FISH discordance, i.e., with gene
      amplification, but no protein overexpression. Both cases would have had no gene
      amplification if the alternative FISH criterion had been used. In conclusion,
      aneusomy 17 is common in breast cancer. Except in a certain subset of cases,
      aneusomy 17 probably is not a significant factor for HER-2/neu protein expression
      or for clinical assessment of HER-2/neu status.

PMID- 11850543
TI  - Mutation analysis of human cytokeratin 8 gene in malignant rhabdoid tumor: a
      possible association with intracytoplasmic inclusion body formation.
AB  - The rhabdoid cell, which is typically observed in malignant rhabdoid tumor (MRT)
      and other malignant neoplasms, has an eosinophilic cytoplasm containing a
      spheroid perinuclear inclusion body. This distinct cell is known to act as a
      highly aggressive indicator in many types of malignant tumors and is
      characterized by aggregates of intermediate filaments, comprising both vimentin
      and cytokeratin (CK) 8, which is mainly expressed in simple-type epithelium such
      as liver and intestine. To clarify the cause of the inclusion body formation, we
      analyzed the alteration of the complete human CK8 gene (KRT 8: 1724 base pairs)
      in seven samples of MRT (three from frozen materials and four from cultured cell
      lines) by reverse-transcriptase polymerase chain reaction, followed by direct
      sequencing. In addition, the two cell lines, Huh7 and HeLa, which lacked rhabdoid
      feature, six pediatric malignant tumors, including three cases of primitive
      neuroectodermal tumor (PNET) and three of Wilms' tumor; and 15 normal liver
      tissue (as a control) were also analyzed. All MRT samples had missense mutations
      in the human KRT 8 gene, i.e., Arg89 --> Cys (5/7); Arg --> Cys251 (3/7); Glu267 
      -> Lys (6/7); Ser290 --> Ile, Met; (7/7) and Arg301 --> His(4/7), none of which
      was detected in any control samples. Among these mutations, the most noteworthy
      findings were that Arg89 belongs to the H1 subdomain of the head domain and that
      Arg251 belongs to the short nonhelical linker segment, or L1-2. Both these
      mutations are noted for their relationships to lateral protofilament
      protofilament interactions. In addition, Ser290 has been previously reported to
      be a phosphorylation site, which has been recognized to play an important role in
      filament organization, leading to conformational change of the CK8 filaments. In
      conclusion, mutated codons of CK8 gene in MRT were located in the important
      region involved in the conformational change of intermediate filament.

PMID- 11850544
TI  - Mucinous nonneoplastic cyst of the pancreas: a novel nonneoplastic cystic change?
AB  - Cystic lesions and neoplasms of the pancreas are uncommon, but they are of
      special interest because they can usually be cured by resection. During the last
      decade, the spectrum of these tumors has increased considerably. We present a
      series of five cystic lesions of the pancreas that differ from all categories
      described so far. The patients affected by these tumors were three men and two
      women (mean age, 57 y). Four lesions were unifocal and involved the head of the
      pancreas; one was multifocal and involved the pancreatic head and tail. Grossly,
      these tumors presented as unilocular or multilocular thin-walled cysts that
      contained turbid fluid, or, in two cases, blood, and lacked any communication
      with the duct system. Microscopically, the cysts were lined by cuboidal to
      columnar mucin-producing cells, supported by a small band of dense fibrous
      stroma. Immunocytochemically, the epithelial cells were positive for cytokeratins
      7, 8, 18, 19, and 20 (except one), and Ca 19-9 but were negative for trypsin,
      CEA, synaptophysin, chromogranin A, calretinin, and alpha-inhibin. In four of the
      five lesions, the epithelial cells expressed MUC5AC, and in one of the five,
      MUC1. MUC2 and MUC6 were not expressed in any of the lesions. The stromal cells
      lacked the nuclear progesterone positivity that is typical of mucinous cystic
      neoplasms. During a mean follow-up period of 2 years, there were no recurrences
      or cases of malignant transformation after resection. The results suggest that
      these cystic lesions are distinct from mucinous cystic neoplasms, the most
      important entity in the differential diagnosis. Because they may represent a
      nonneoplastic cystic change of the pancreas, we propose the descriptive term
      mucinous nonneoplastic cyst for these tumors of unknown pathogenesis.

PMID- 11850545
TI  - Quantification of MYCN, DDX1, and NAG gene copy number in neuroblastoma using a
      real-time quantitative PCR assay.
AB  - Amplification of the proto-oncogene MYCN is a strong adverse prognostic factor in
      neuroblastoma patients in all tumor stages. The status of the MYCN gene has
      become an important factor in clinical decision making and therapy
      stratification. Consequently, fast and accurate assessment of MYCN gene copy
      number is of the utmost importance and the use of two independent methods to
      determine MYCN status is recommended. For these reasons we have developed and
      evaluated a real-time quantitative PCR (Q-PCR) assay as an alternative for time
      consuming Southern blot analysis (SB), and as a second independent technique in
      parallel with fluorescence in situ hybridization (FISH) analysis. Advantages of Q
      PCR are a large dynamic range of quantification, no requirement for post-PCR
      sample handling and the need for very small amounts of starting material. The
      accuracy of the assay was illustrated by measurement of MYCN single gene copy
      changes in DNA samples of two patients with 2p deletion and duplication,
      respectively. Two different detection chemistries i.e., a sequence specific
      TaqMan probe and a generic DNA binding dye SYBR Green I were evaluated and shown
      to yield similar results. Also, two different calculation methods for copy number
      determination were used i.e., the kinetic method and the comparative C(T) method,
      and shown to be equivalent. In total, 175 neuroblastoma samples with known MYCN
      status, as determined by FISH and/or SB, were examined. Q-PCR data were highly
      concordant with FISH and SB data. In addition to MYCN copy number evaluation,
      DDX1 and NAG gene copy numbers were determined using a similar Q-PCR strategy.
      Survival analysis pointed out that DDX1 and/or NAG amplification has no
      additional adverse effect on prognosis.

PMID- 11850546
TI  - Multiple angiomyolipomata of the liver: a case report.
AB  - Angiomyolipoma (AML) is a rare benign tumor that occurs most commonly in the
      kidney. Occasionally it may be found in the liver. Lesions in the liver are
      usually solitary. Multiple AMLs are extremely rare and are typically seen in
      patients with tuberous sclerosis. We now report an unusual case of a 46-year-old
      woman with multiple hepatic AMLs. There were more than 15 lesions distributed
      predominantly in the right hepatic lobe. The tumors ranged from 0.2 to 6 cm in
      size and consisted of a variable admixture of proliferating blood vessels,
      adipose tissue, and smooth muscle. There was no clinical evidence of tuberous
      sclerosis in this patient. Polymerase chain reaction amplification of the highly
      polymorphic human androgen receptor gene (HUMARA) was performed and the pattern
      of X chromosome inactivation was analyzed. Three of the five representative AML
      nodules showed a preferential loss of one of the two HUMARA alleles indicating a
      clonal proliferation with involvement of different alleles. Histologic
      examination of the corresponding lesions showed clonal lesions to be
      predominantly composed of epithelioid myoid cells while the polyclonal lesions
      were predominantly composed of adipose tissue. While the histologic diagnosis of
      AML in a surgical resection specimen is often straightforward, the radiographic,
      cytologic and intra-operative interpretation of a case with multiple lesions
      presents a considerable challenge.

PMID- 11850547
TI  - Genital tract tumors in Proteus syndrome: report of a case of bilateral
      paraovarian endometrioid cystic tumors of borderline malignancy and review of the
      literature.
AB  - Proteus syndrome is a rare, sporadic disorder that causes postnatal overgrowth of
      multiple tissues in a mosaic pattern. Characteristic manifestations include:
      overgrowth and hypertrophy of limbs and digits, connective tissue nevus,
      epidermal nevus and hyperostoses. Various benign and malignant tumors and
      hamartomas may complicate the clinical course of patients with the syndrome.
      Commonly encountered tumors include hemangiomas, lymphangiomas and lipomas.
      Tumors of the genital tract occur less often. Bilateral ovarian cystadenomas are
      regarded as having diagnostic value in Proteus syndrome when occurring within the
      first two decades of life. We describe a 3-year-old girl with Proteus syndrome
      who developed bilateral paraovarian villoglandular endometrioid cystadenomatous
      tumors of borderline malignancy (low malignant potential) of the broad ligament.
      Desmoplastic tumor implants, presumably noninvasive, were present in biopsies
      from the pelvic floor, cul-de-sac and omentum. This is the first recognized
      example of a cystic borderline epithelial tumor of the female genital tract and
      the first paraovarian tumor reported in a patient with Proteus syndrome.
      Previously reported tumors and cystic lesions involving the female genital tract
      and the male genital tract in patients with Proteus syndrome are reviewed. We
      suspect that specific testicular and paratesticular tumors may prove to have the
      same diagnostic value in Proteus syndrome as do bilateral cystic ovarian and
      paraovarian tumors.

PMID- 11850548
TI  - Indoor air quality guidelines.

PMID- 11850549
TI  - Occupational risk of Lyme disease: an epidemiological review.
AB  - Lyme disease is the most common vector borne disease in the United States. Since
      the early 1980s, a large body of literature has evaluated the occupational risk
      of Lyme disease. The availability of a new vaccine to prevent Lyme disease makes
      it necessary for occupational health professionals to make decisions regarding
      the occupational risk of the disease among employees.

PMID- 11850550
TI  - Occupational accidents aboard merchant ships.
AB  - OBJECTIVES: To investigate the frequency, circumstances, and causes of
      occupational accidents aboard merchant ships in international trade, and to
      identify risk factors for the occurrence of occupational accidents as well as
      dangerous working situations where possible preventive measures may be initiated.
      METHODS: The study is a historical follow up on occupational accidents among crew
      aboard Danish merchant ships in the period 1993-7. Data were extracted from the
      Danish Maritime Authority and insurance data. Exact data on time at risk were
      available. RESULTS: A total of 1993 accidents were identified during a total of
      31 140 years at sea. Among these, 209 accidents resulted in permanent disability
      of 5% or more, and 27 were fatal. The mean risk of having an occupational
      accident was 6.4/100 years at sea and the risk of an accident causing a permanent
      disability of 5% or more was 0.67/100 years aboard. Relative risks for notified
      accidents and accidents causing permanent disability of 5% or more were
      calculated in a multivariate analysis including ship type, occupation, age, time
      on board, change of ship since last employment period, and nationality.
      Foreigners had a considerably lower recorded rate of accidents than Danish
      citizens. Age was a major risk factor for accidents causing permanent disability.
      Change of ship and the first period aboard a particular ship were identified as
      risk factors. Walking from one place to another aboard the ship caused serious
      accidents. The most serious accidents happened on deck. CONCLUSIONS: It was
      possible to clearly identify work situations and specific risk factors for
      accidents aboard merchant ships. Most accidents happened while performing daily
      routine duties. Preventive measures should focus on workplace instructions for
      all important functions aboard and also on the prevention of accidents caused by
      walking around aboard the ship.

PMID- 11850551
TI  - Risk of birth defects by parental occupational exposure to 50 Hz electromagnetic
      fields: a population based study.
AB  - OBJECTIVES: To study the risk of birth defects by parental occupational exposure
      to 50 Hz electromagnetic fields. METHODS: The Medical Birth Registry of Norway
      was linked with census data on parental occupation. An expert panel constructed a
      job exposure matrix of parental occupational exposure to 50 Hz magnetic fields.
      Exposure to magnetic fields was estimated by combining branch and occupation into
      one of three exposure levels: <4 hours, 4-24 hours, and >24 hours/week above
      approximately 0.1 mu T. Risks of 24 categories of birth defects were compared
      across exposure levels. Out of all 1.6 million births in Norway in the period
      1967-95, 836,475 and 1,290,298 births had information on maternal and paternal
      exposure, respectively. Analyses were based on tests for trend and were adjusted
      for parents' educational level, place of birth, maternal age, and year of birth.
      RESULTS: The total risk of birth defects was not associated with parental
      exposure. Maternal exposure was associated with increased risks of spina bifida
      (p=0.04) and clubfoot (p=0.04). A negative association was found for isolated
      cleft palate (p=0.01). Paternal exposure was associated with increased risks of
      anencephaly (p=0.01) and a category of "other defects" (p=0.02). CONCLUSION: The
      present study gives an indication of an association between selected disorders of
      the central nervous system and parental exposure to 50 Hz magnetic fields. Given
      the crude exposure assessment, lack of comparable studies, and the high number of
      outcomes considered, the results should be interpreted with caution.

PMID- 11850552
TI  - A cohort mortality and nested case-control study of French and Austrian talc
      workers.
AB  - OBJECTIVES: To study whether the mortality from non-malignant and malignant
      respiratory diseases of workers employed in French and Austrian talc mines and
      mills is related to their long term occupational exposure. METHODS: Two
      historical cohorts were set up comprising all male subjects who had been working
      continuously for at least 1 year in a series of talc producing companies in
      France and Austria. The French cohort consisted of those employed at a site in
      the French Pyrenees and working between 1 January 1945 and 31 December 1994. The
      Austrian cohort consisted of the workers employed between 1 January 1972 and 31
      December 1995 in one of four industrial sites in the Austrian Alps. The mortality
      within the cohorts was compared with local death rates. Two nested case-control
      studies focusing on non-malignant and malignant respiratory diseases were set up
      to estimate possible dose-response relations with cumulative exposure to talc
      dust based on an industry specific job exposure matrix. RESULTS: Mortality from
      lung cancer was in small excess in both cohorts (France, standardised mortality
      ratio (SMR) 1.23, 21 cases observed, 95% confidence interval (95% CI) 0.76 to
      1.89; Austria, SMR 1.06, seven observed, 95% CI 0.43 to 2.19). A non-significant
      excess mortality was found for all non-malignant respiratory diseases in the
      French cohort due to a significant excess for pneumoconiosis (SMR 5.56, three
      observed, 95% CI 1.12 to 16.2). The case-control study of non-malignant
      respiratory disease showed an increased mortality in the highest exposure groups
      (odds ratio (OR) 2.5 for a cumulative exposure > or = 800 y.mg/m(3)) with a
      significant trend (OR/100 y.mg/m(3) 1.08) with cumulative exposure to talc. On
      the contrary, no increasing trend could be found in the case-control study of
      lung cancer. This result must be interpreted considering the small cohort size.
      Adjustment on smoking and exposure to quartz did not influence these results to
      any extent. CONCLUSIONS: The mortality from non-malignant respiratory disease was
      found to be related to high cumulative exposure to talc dust. The small excess in
      lung cancer does not seem to be attributable to talc.

PMID- 11850553
TI  - Upper airway inflammation and respiratory symptoms in domestic waste collectors.
AB  - OBJECTIVES: To compare respiratory symptoms and upper airway inflammation in
      domestic waste collectors and controls, and to find the association between
      measures of upper airway inflammation on the one hand and exposure concentrations
      of organic dust or respiratory symptoms on the other hand. METHODS: In a cross
      sectional study among 47 waste collectors and 15 controls, questionnaire data on
      respiratory symptoms were collected. Nasal lavage (NAL), to assess upper airway
      inflammation, was performed before and after a work shift at the beginning and at
      the end of the working week. In NAL fluid, cells were counted and differentiated
      and concentrations of interleukin 6 (IL6), IL8, tumour necrosis factor-alpha (TNF
      alpha), and IL1 beta were measured. In collectors, inhalable dust samples were
      collected in which bacterial endotoxin and mould beta(1-->3)-glucan were
      assessed. RESULTS: Prevalence of respiratory symptoms was higher in waste
      collectors than in controls. Geometric mean exposure concentrations were 0.58
      mg/m(3) for dust, 39 EU/m(3) for endotoxin, and 1.3 microg/m(3) for beta(1-->3)
      glucan. At the end of the week collectors had higher concentrations of total
      cells and IL8 in NAL before and after a shift than controls (cells, before 1.9
      fold p<0.10, after 3.3-fold p<0.01; IL8, before and after 1.8-fold p<0.05), and
      after/before work shift ratios of total cells were also higher (2.3-fold p=0.06)
      in collectors than in controls. Cells in NAL fluid consisted predominantly of
      neutrophils and epithelial cells, whereas eosinophils and mononuclear cells were
      rarely found. Exposure to dust and endotoxin was associated with concentrations
      of IL8 after the shift (p<0.05). Increased concentrations of IL8 (p<0.05) and
      total cells (p<0.10) after the shift were associated with respiratory symptoms.
      Concentrations of IL6, TNF alpha, and IL1 beta were not associated with waste
      collecting, symptoms, or exposure. CONCLUSIONS: Waste collectors show signs of
      increased upper airway inflammation and respiratory symptoms compared with
      controls. Exposure to organic dust probably underlies the inflammation mediated
      by neutrophils that result in respiratory symptoms.

PMID- 11850556
TI  - Effect of air pollution and environmental tobacco smoke on serum hyaluronate
      concentrations in school children.
AB  - OBJECTIVES: To evaluate serum hyaluronate concentrations relative to air
      pollution, environmental tobacco smoke (ETS), and respiratory health in Japanese
      school children. METHODS: Respiratory symptoms and serum IgE concentrations were
      examined in 1037 school children living in four communities in Japan with
      differing levels of air pollution. Serum hyaluronate concentrations were assayed
      in 230 children, consisting of all the children who had symptoms of either asthma
      or wheeze (65 and 50 subjects, respectively) and normal controls adjusted for
      sex, school grade, and school without these symptoms (115 subjects). RESULTS:
      Although serum hyaluronate concentrations did not differ for either asthma or
      wheeze, the concentrations were significantly higher in children living in
      communities with higher levels of air pollution. Children with asthma or wheeze
      and those with serum IgE concentrations of 250 IU/ml or above showed differences
      in hyaluronate concentrations that related to the degree of air pollution in the
      communities. In children with higher serum IgE concentrations, the hyaluronate
      concentrations among subjects exposed to ETS were significantly higher than among
      those without exposure to ETS. CONCLUSIONS: The present results suggest that
      serum hyaluronate concentration is related to the degree of air pollution and
      exposure to ETS. Children with asthma or wheeze and children with higher IgE
      concentrations are considered to be more susceptible to environmental factors.

PMID- 11850555
TI  - Incidence of asthma in female Swedish hairdressers.
AB  - OBJECTIVE: To investigate the risk of asthma in hairdressers. METHODS: The
      incidence of asthma was retrospectively estimated in a Swedish nationwide study
      including all female hairdressers certified from vocational schools from 1970 to
      1995, and a stratified sample of women from the general population were
      referents. A postal questionnaire included questions on respiratory tract
      symptoms, atopy, smoking, working periods as a hairdresser, and number of
      specific hair treatments performed/week. Reported exposures were validated by
      occupational hygienists. Rate ratios of incidence (IRRs) of asthma were estimated
      by Poisson regression, adjusted for calendar year of observation, hay fever,
      smoking, and region of domicile. RESULTS: The crude incidences of asthma/1000
      person-years were: 3.9 during active years as a hairdresser, 2.8 among the
      hairdressers when not working in the profession, and 3.1 among the referents. The
      corresponding IRR for being an active hairdresser compared with the referents was
      1.3 (95% confidence interval (95% CI) 1.0 to 1.6). Moderate effects on risk of
      asthma were found both from hairdressing work (IRR=1.6 (1.1 to 2.2) among never
      smokers) and from smoking (IRR=1.6 (1.2 to 2.2) among referents). However, the
      combined effect from hairdressing work and smoking (IRR=1.5 (1.0 to 2.1)) was
      less than expected (p=0.02). No effect modification by respiratory atopy was
      found. The hairdressers most often performing hair bleaching treatments (IRR=1.5
      (0.7 to 3.0)) or using hair spray (IRR=1.4 (0.8 to 2.4)) had, compared with the
      most infrequent users, a slightly, but not significantly higher incidence of
      asthma. Exposure to persulphates in hair bleach was estimated to be 0.04-0.15
      mg/m(3) during mixing of the powder. Reported average number of bleaching
      treatments agreed well with those performed according to a diary. CONCLUSIONS:
      Active hairdressing work was associated with a moderately increased incidence of
      asthma among lifelong non-smokers. The results are moderately supportive, but not
      conclusive, of associations between asthma and exposure to hair bleach or hair
      spray.

PMID- 11850554
TI  - Nested case-control study of lung cancer in four Chinese tin mines.
AB  - OBJECTIVES: To evaluate the relation between occupational dust exposure and lung
      cancer in tin mines. This is an update of a previous study of miners with high
      exposure to dust at four tin mines in southern China. METHODS: A nested case
      control study of 130 male lung cancer cases and 627 controls was initiated from a
      cohort study of 7855 subjects employed at least 1 year between 1972 and 1974 in
      four tin mines in China. Three of the tin mines were in Dachang and one was in
      Limu. Cumulative total exposure to dust and cumulative exposure to arsenic were
      calculated for each person based on industrial hygiene records. Measurements of
      arsenic, polycyclic aromatic hydrocarbons (PAHs), and radon in the work sites
      were also evaluated. Odds ratios (ORs), standard statistic analysis and logistic
      regression were used for analyses. RESULTS: Increased risk of lung cancer was
      related to cumulative exposure to dust, duration of exposure, cumulative exposure
      to arsenic, and tobacco smoking. The risk ratios for low, medium, and high
      cumulative exposure to dust were 2.1 (95% confidence interval (95% CI) 1.1 to
      3.8), 1.7 (95% CI 0.9 to 3.1), and 2.8 (95% CI 1.6 to 5.0) respectively after
      adjustment for smoking. The risk for lung cancer among workers with short,
      medium, and long exposure to dust were 1.9 (95% CI 1.0 to 3.5), 2.3 (95% CI 1.3
      to 4.1), and 2.3 (95% CI 1.2 to 4.2) respectively after adjusting for smoking.
      Several sets of risk factors for lung cancer were compared, and the best
      predictive model included tobacco smoking (OR=1.6, 95% CI 1.1 to 2.4) and
      cumulative exposure to arsenic (ORs for different groups from low to high
      exposure were 2.1 (95% CI 1.1 to 3.9); 2.1 (95% CI 1.1 to 3.9); 1.8 (95% CI 1.0
      to 3.6); and 3.6 (95% CI 1.8 5 to 7.3)). No excess of lung cancer was found among
      silicotic subjects in the Limu tin mine although there was a high prevalence of
      silicosis. Exposures to radon were low in the four tin mines and no carcinogenic
      PAHs were detected. CONCLUSIONS: These findings provide little support for the
      hypothesis that respirable crystalline silica induces lung cancer. Ore dust in
      work sites acts as a carrier, the exposure to arsenic and tobacco smoking play a
      more important part in carcinogenesis of lung cancer in tin miners. Silicosis
      seems not to be related to the increased risk of lung cancer.

PMID- 11850558
TI  - Smoking and mortality in 81,344 drivers in Guangzhou, China.
AB  - OBJECTIVES: Previous studies on drivers focused on the effect of their exposure
      to vehicle exhaust and there is little evidence of the effect of smoking. This
      cohort analytical study aimed to examine the mortality of drivers relative to
      smoking and professional driving in Guangzhou, China. METHODS: Information on
      demographic characteristics, type of driver (professional and non-professional),
      smoking, and drinking were retrieved from medical records of drivers who applied
      for driving licences from March to December 1992. Vital status and causes of
      death of 81,344 men aged 30 or above were ascertained to the end of September
      1999 (follow up, mean=7.14 years, median=7.17 years). RESULTS: At baseline, the
      mean (SD) age was 40.8 (5.6) years. One third were professional drivers; 49.0%
      were daily smokers. 858 Deaths were identified. The relative risk of overall
      mortality for ever smoking was 1.24 (95% confidence interval (95% CI) 1.07 to
      1.44) after adjusting for age, alcohol drinking, education, and type of drivers.
      Compared with non-professional drivers, professional drivers had similar risks of
      death, and their relative risk of overall mortality for ever smoking was 1.35
      (1.06 to 1.71). CONCLUSIONS: Smoking is a more important cause of death than
      professional driving itself. The results show serious public health problems in
      the early stage of the tobacco epidemic and support urgent measures to help
      drivers stop smoking.

PMID- 11850560
TI  - Molecular medicine---an overview.

PMID- 11850561
TI  - Orthopaedic ice-skating injuries in a regional hospital in Hong Kong.
AB  - Ice-skating is a popular sport in Hong Kong. Since the opening of our hospital,
      we have observed a special pattern of injury related to ice-skating. Individuals
      have had a wide range of injuries including fractures and deep tissue
      lacerations, many of which have needed operative intervention. Public awareness
      of the risks remains low. The pattern and mechanisms of injury, management
      modalities, and contributing factors to the injuries are discussed. Preventive
      measures and socioeconomic implications are also discussed.

PMID- 11850559
TI  - Complementary and alternative medicine: what is it all about?

PMID- 11850562
TI  - Urolume prostatic stents for urinary retention due to benign prostatic
      hyperplasia in patients with high medical risks.
AB  - A retrospective study was conducted to evaluate the efficacy of using urolume
      prostatic stents in patients who have developed urinary retention due to benign
      prostatic hyperplasia but who are medically unfit for conventional transurethral
      resection of the prostate. From April 1995 through May 1996, 12 patients were
      studied (mean age, 80 years; range, 72-92 years). Pre-operative assessment
      pointed to major risk due to an underlying medical condition. Flexible cystoscopy
      and video-urodynamcis were performed to assess the detrusor function and to
      ascertain if prostatic obstruction was the cause of retention. After insertion of
      the prostatic stent, 11 patients managed to void on recovery from the anaesthesia
      and remained catheter-free during a mean follow up period of seven months (range,
      2-18 months). There was no operative morbidity or mortality. Urolume prostatic
      stents represent a viable option for elderly patients with significant medical
      risks who have urinary retention. Pre-operative urodynamics are essential to
      identify appropriate candidates.

PMID- 11850563
TI  - Recent changes in the pattern of hand injuries in Hong Kong: a regional hospital
      survey.
AB  - Adult inpatients with injuries to the hand admitted to the Department of
      Orthopaedics and Traumatology of the Prince of Wales Hospital, Hong Kong, from
      June 1992 to May 1993 were surveyed (n=533). The causes of injury, mechanisms
      involved, and the nature of injuries were recorded. The injuries were further
      graded according to four different scales. It was found that 65% of the injuries
      were sustained at work, 15% in domestic environments, 7.6% during sports or
      recreational activities, and 6.5% in traffic accidents. Injuries caused by heavy
      machinery amounted to 26.7% and the electric saw was the second most common cause
      of injury accounting for 9.4% of injuries. Crush injuries occurred in 37.8%. The
      incidence of hand injury is estimated to be 600 per 100,000 population annually.
      The pattern of hand injuries bears some similarities and differences to published
      series. A comparison with data obtained in Hong Kong in the 1970s shows that
      major changes have occurred. We need continual surveillance of hand injury
      patterns.

PMID- 11850564
TI  - Acute appendicitis---a recent audit of an old problem.
AB  - We conducted a retrospective review of all patients who had an appendicectomy
      performed at the Queen Elizabeth Hospital, Hong Kong, from January 1993 through
      December 1994. The diagnostic accuracy for true appendicitis was 74%. Nine per
      cent of patients had other pathologies, which also needed exploration. The
      diagnostic accuracy in female patients was 66%, compared with 82% for male
      patients (P<0.0001). Female patients aged between 15 to 40 years were diagnosed
      accurately 62% of the time, which has significantly lower than the rate for other
      female patients (P=0.016). the overall morbidity and mortality rates were 9.2%
      and 3%, respectively. Complicated appendicitis had a higher morbidity rate of
      21%, compared with 9% for uncomplicated appendicitis (P<0.0001). Results for
      patients who were operated on the day of admission were compared with those who
      were operated on the day after admission. No significant difference in diagnostic
      accuracy (P=0.46), percentage of complicated appendicitis (P=0.7), and morbidity
      rate (P=0.8) was found.

PMID- 11850557
TI  - Effects of air pollution on changes in lung function induced by exercise in
      children with chronic respiratory symptoms.
AB  - OBJECTIVE: To investigate how daily variations in ambient air pollution,
      especially in particles, during the cold of winter affect repeated measurements
      of baseline lung function and exercise induced bronchial responsiveness among
      primary school children with chronic respiratory symptoms. METHODS: During
      alternate school weeks (maximum five) from February to April 1994, 33 children
      took part in exercise challenge tests (n=141 tests). The exercise challenges were
      conducted outdoors in a school yard in the centre of Kuopio, Finland. Spirometric
      lung functions were measured indoors before the exercise, and 3 and 10 minutes
      after. Daily mean concentrations of PM(10), black smoke (BS), NO(2), CO, SO(2),
      and particle size and numbers were monitored at a nearby fixed monitoring site.
      RESULTS: Daily variations in ambient air pollution were not associated with
      enhanced bronchial responsiveness. However, increased concentrations of BS,
      PM(10), particle numbers, NO(2), and CO were consistently associated with an
      impairment of baseline lung functions. The reductions in forced vital capacity
      (FVC) and forced expiratory volume in 1 second (FEV(1)) were 0.5% and 0.6%,
      respectively, for each 10 microg/m(3) increase in BS (lag 2). CONCLUSION:
      Particles derived from combustion affect baseline lung function rather than
      bronchial responsiveness among children with chronic respiratory symptoms.

PMID- 11850565
TI  - A review of laparoscopy and laparotomy in the management of tubal pregnancy.
AB  - A retrospective review was performed of all women who had undergone operation for
      a tubal pregnancy at the Prince of Wales Hospital, Hong Kong, from November 1992
      to March 1994. One hundred and five patients were included---61 were managed by
      laparoscopy and 44 by laparotomy. There were no differences in age, parity,
      gestational age, frequency of previous ectopic pregnancy, or laparotomy between
      the two groups. Sixty per cent of patients in the laparotomy group had a
      diagnostic laparoscopy prior to the laparotomy. The laparoscopy group had a lower
      incidence of haemoperitoneum (45.9% vs 75.0%, P<0.05). There was no difference in
      the mean operating time. The laparoscopic approach was associated with a
      significant reduction in: intra-operative blood loss (46.7plus minus76.8 mL vs
      213.4plus minus149.3 mL. P<0.001), post-operative analgesia requirement (odds
      ratio 0.08, 95% CI, 0.02-0.32), post-operative morbidity (odds ratio 0.27, 95%
      CI, 0.12-0.58), length of hospital stay (2.9plus minus2.2 days vs 5.1plus
      minus1.2days, P<0.001) and recuperation period (11.0plus minus9.3days vs 21.7plus
      minus8.5 days, P<0.001). Operative laparoscopy has the advantage of combining
      diagnostic and therapeutic procedures in a single operation, and is a better
      approach than laparotomy in the management of tubal pregnancy.

PMID- 11850567
TI  - Gene therapy---perspectives and promises.
AB  - Gene therapy is a novel and promising treatment for inherited and acquired
      genetic disorders. Basic laboratory investigations and clinical trials have shown
      that gene therapy in vivo is feasible, results in biological responses, and is
      relevant to different types of human diseases, To achieve clinical efficacy,
      current research had focused on improving the efficiency and specificity of gene
      transfer. Furthermore, gene therapy unlocks new research approaches and offers
      important insights into disease mechanisms. The emphasis of gene therapy has also
      shifted from the treatment of inherited genetic diseases to cancer. Despite the
      significant progress made in our understanding of gene therapy, considerable
      conceptual and practical limitations still exist. Evidence of the efficacy of
      gene therapy, however, is compelling. Many of the current problems of gene
      therapy should be overcome and gene therapy will become an important treatment
      modality for genetic diseases.

PMID- 11850566
TI  - A survey of the long term outcome of elderly stroke survivors and the needs of
      their carers.
AB  - A survey was conducted to assess the long term outcome of 60 elderly stroke
      survivors (mean age, 81.7 years). Of these patients, 48% died within one year of
      discharge and 79% of the mortality occurred in the first six months. Patients
      discharged to institutions after the initial stroke had a significantly higher
      risk of death in one year (relative risk=1.47) compared with those who were
      discharged home. For those who survived for a mean period of 18.6months, 72%
      (21/29) were institutionalised. This group had significantly worse functional
      status and mobility compared with those who were living at home. The caring of
      elderly stroke patients was considered a heavy burden for most carers at home or
      in institutions and the need for medical and social support was great.

PMID- 11850568
TI  - Prenatal diagnosis of common single gene disorders by DNA technology.
AB  - Using the new DNA technology, it is now possible to offer prenatal diagnosis or
      presymptomatic testing for many genetic diseases. For prenatal diagnosis, foetal
      tissue is obtained by chorionic villus sampling at 9 to 11 weeks gestation or
      amniocentesis at 18 weeks. The programme in Hong Kong, which started in 1982, is
      reviewed here and now included alpha and beta thalassaemia, haemophilia A and B,
      Duchenne muscular dystrophy, Huntington's diseases, and spinal muscular atrophy.
      DNA diagnosis can now be performed using a single cell obtained from pre
      implantation embryos or from rare foetal cells isolated from maternal peripheral
      blood. The latter is safer and more acceptable to parents. Presymptomatic testing
      for untreatable diseases such as Hungtington's disease poses new ethical and
      social problems that need to be resolved. As many more genes are being
      discovered, prenatal diagnosis and presymptomatic testing programmes will
      continue to meet new challenges in the future.

PMID- 11850570
TI  - Molecular basis of cancer.
AB  - Cancer, for the most part, is caused by multiple somatic mutations in a single
      cell and its progeny. However, in some individuals, constitutional genetic
      alterations may also play a role. Depending on the specific cell type, the
      affected cell and its progeny accumulate sequential mutations and sustain
      multiple genetic alterations over decades. The defective genetic anomalies lead
      to disabled critical cellular pathways, which with DNA replications in between,
      evolve clonally and expand into a malignant phenotype. Additional mutations in
      some genes confer a further selective growth advantages and the neoplastic
      process progresses to invade surrounding tissues and metastasise to other organs.

PMID- 11850569
TI  - Nucleic acid technology and infectious diseases.
AB  - The past decade has witnessed an explosion in the knowledge of microbial
      genetics, pathogenesis, and antimicrobial resistance as a result of advances in
      molecular technology. This has brought important breakthroughs in the management
      of patients with infectious diseases, as organisms that had previously been
      difficult to demonstrate in vitro can now be detected by molecular techniques
      such as the polymerase chain reaction. Not only is rapid diagnosis now possible,
      but old diseases of uncertain aetiology have been found to have an infective
      origin, for instance, Whipple's disease. Molecular technology has also
      contributed greatly to epidemiological studies of outbreaks, understanding
      antimicrobial resistance, developing new antimicrobial agents, the in vitro
      synthesis of immunomodulators, production of vaccines, and gene therapy. The
      limitations of these latest technologies, however, need to be remembered so that
      they yield meaningful information for patient care.

PMID- 11850571
TI  - Molecular detection of minimal residual disease for patients with leukaemia and
      lymphoma.
AB  - Although a complete clinical remission can often be achieved with chemotherapy
      for patients with leukaemia and lymphoma, relapses still occur. Residual tumour
      cells probably have survived therapy and account for subsequent disease relapse.
      The sensitivity of conventioned ways of detecting residual tumour cells, such as
      morphological studies, immunophenotyping, and cytogenetics, is only about 1% to
      5% and may be inadequate. Polymerase chain reaction technology has provided a
      simple and highly sensitive means for the detection of minimal residual disease.
      The technology has been successfully applied to study biopsy samples obtained
      from patients with leukaemia and lymphpma. Its clinical usefulness, however,
      requires further evaluation by prospective clinical studies.

PMID- 11850572
TI  - Mouse models for human diseases.
AB  - Mice are increasingly being used as models for the study of various human
      diseases. This is primarily because among mammalian modals, they are most
      amenable to genetic manipulations. As we attempt to understand the molecular
      mechanism of diseases, it is imperative that the genes involved in the disease
      process be identified. One approach is to study mouse mutants with symptoms
      analogous to human diseases, and try to identify the genes responsible. Another
      approach is to manipulate the expression of genes suspected to be involved and
      see how they affect the disease development. This review briefly discusses the
      concept of manipulating gene expression by transgenic and gene knockout
      technology and illustrates this with how these technique are used to study the
      mechanism of diabetic complications.

PMID- 11850573
TI  - Allergic sensitisation to common environmental allergens in adult asthmatics in
      Hong Kong.
AB  - The relationship between immediate skin reactivity to common allergens and adult
      asthma is not well defined. We retrospectively evaluated the profile of allergen
      sensitisation to common environmental allergens in 666 adult asthma patients at
      an asthma clinic in a teaching hospital in Hong Kong. Four hundred and seventy
      one asthmatics (70.7%) were atopic; there were more males than females, although
      the difference did not reach statistical significance. The skin test positively
      rate decreased significantly with age so that asthmatics aged 35 years and older
      were four to six times less likely to be atopic and eight to 12 times less likely
      to be allergic to Dermatophagoides pteronyssinus, compared with young asthmatics
      aged 15 to 24 years (P<0.001). Inhalant allergy was more common than food allergy
      and of the inhalants, indoor allergens, including house dust mite and cockcoach
      were more important than outdoor allergens. The allergens most frequently
      associated with positive skin tests were D. pteronyssinus (62.2%), D. farinae
      (60%), cockroach (40.7%), cat dander (24.0%), and royal jelly (16.8%). In
      conclusion, allergen sensitisation is common in adult asthmatics in Hong Kong,
      and allergen avoidance should be included as part of the preventive strategies
      for controlling the disease in the community.

PMID- 11850574
TI  - The management of intermittent claudication.
AB  - Intermittent claudication is a common symptom. It is a marker of generalised
      antherosclerotic disease and may herald other cardiovascular catastrophes. The
      aim of management is to reduce the total cardiovascular morbidity and mortality.
      The functional status and quality of life of severely affected patients can be
      improved by endovascular and surgical interventions.

PMID- 11850575
TI  - Silastic medialization for unilateral vocal fold palsy.
AB  - From August 1994 to September 1995, 12 silastic medialization procedures were
      performed for the treatment of vocal fold palsy. The causes included tuberculous
      fibrosis, carcinoma of the bronchus, post-oesophagectomy for carcinoma of the
      oesophagus and idiopathy. Early operation was performed in cases due to malignant
      conditions to relieve symptoms. In those with benign conditions, operation was
      performed if conservative treatment failed to control the symptoms in six months.
      The efficacy of silastic medialization for the treatment of dysphonia was
      evaluated by both subjective and objective voice assessment. The results indicate
      that the procedure is effective in the relief of dysphonia in unilateral vocal
      fold palsy. Only one patient in the study required a revision operation due to
      unsatisfactory voice quality. The procedure has the advantages of being tunable,
      reversible, and suitable for old and debilitated patients. The long term benefits
      of the procedure require further study.

PMID- 11850576
TI  - Computed tomography-guided stereotactic aspiration and biopsy of a cystic
      metastatic adenocarcinoma of the pons.
AB  - We herein report a case of adenocarcinoma of the right main bronchus disseminated
      to the pons, left cerebral peduncle, and liver. Computed tomography-guided Cosman
      Robert-Wells stereotactic aspiration of the cystic pontine lesion was performed
      through a transoccipital, transtentorial route and a catheter inserted in the
      cyst cavity that was connected to a subgaleal Ommaya reservoir for further
      aspiration and decompression. The choice of this approach to the lesion is
      briefly discussed.

PMID- 11850577
TI  - Obstetric analgesia in Hong Kong.

PMID- 11850578
TI  - Obstetric analgesia in Hong Kong: authors' reply.

PMID- 11850579
TI  - Characteristics of the Baumann's angle in Hong Kong Chinese children.

PMID- 11850580
TI  - Epidemiology of breast cancer in Korea: occurrence, high-risk groups, and
      prevention.
AB  - Breast cancer ranks second or third to uterine cervix cancer and stomach cancer
      as a cause of death in women, and as a common site of primary cancer. The large
      difference in its incidence between Westernized and non-Westernized countries is
      remarkable. There is a linear increase with age that is observed in Western
      countries, which are high-incidence areas, on the contrary to the inverted V
      shape curve seen in Asian countries. Epidemiologic studies conducted in Korea
      have shown that an older age, a family history of breast cancer, early menarche,
      late menopause, late full-term pregnancy, and never having had a breast-fed child
      are primary risk factors in the development of breast cancer. The estrogen
      augmented-by-progesterone hypothesis explains the roles of these factors to some
      extent. On the other hand, recent molecular studies have revealed the existence
      of novel gene environmental interactions. Epidemiological features suggest that
      the breast cancer incidence rate in Korea will increase, but the age specific
      curve would not be changed in keeping with what is observed in Western countries.
      Strategies aimed at controlling breast cancer that include the screening
      guidelines and the identification of individual predispositions may give us
      further insights into both the etiology and the prevention of breast cancer.

PMID- 11850581
TI  - Anti-inflammatory effects of IL-4 and IL-10 on human polymorphonuclear
      leukocytes.
AB  - Inflammatory responses are strictly regulated by coordination of pro-inflammatory
      and anti-inflammatory mediators. Interleukin-4 (IL-4) and interleukin-10 (IL-10)
      have typically the biologic anti-inflammatory effects on monocytes, but uncertain
      effects on polymorphonuclear leukocytes (PMNs). The PMNs are the first line of
      cellular response for host defense during acute inflammation. To modify hyper
      inflammatory reaction with biologic anti-inflammatory mediators, we have
      determined the biologic anti-inflammatory activities of IL-4 and IL-10 on human
      PMNs. Human PMNs were pretreated with IL-4 or IL-10 and then stimulated with
      formyl methionyl leucyl phenylalanine (fMLP) for times indicated. The level of
      H2O2, interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha) were
      determined in the each cell free supernatants. fMLP plays the role of a typical
      pro-inflammatory agent and, at least in determined conditions, down-regulated TNF
      release. IL-4 acts as an anti-inflammatory mediator but IL-10 did not show its
      anti-inflammatory activities on fMLP-stimulated human PMNs. IL-4 and IL-10 have
      different anti-inflammatory mechanisms. Perhaps, IL-10 needs co-factors to act as
      an anti-inflammatory mediator.

PMID- 11850582
TI  - Newly developed mecometer method for objective assessment of meconium content.
AB  - We developed a new method for an objective assessment of the meconium content in
      amniotic fluid. By establishing a standard scale through a serial dilution of a
      known amount of meconium into the amniotic fluid, we developed a new method
      "mecometer" that can objectively measure the meconium content in meconium-stained
      amniotic fluid samples. The objectivity and reliability of this mecometer were
      verified by 300 student volunteers. At least 70% of the volunteers could
      objectively measure and digitally describe the meconium content in meconium
      stained amniotic fluid samples. We believe our newly developed mecometer is a
      very simple, reliable, and portable method, not requiring any instruments.

PMID- 11850583
TI  - Cancers of the upper aerodigestive tract in Korea.
AB  - Cancers of the upper aerodigestive tract (UADT) constitute 3.5-4% of all
      malignancies. Since the majority of cases are squamous cell carcinomas which are
      related with epidemiologic factors, a different pattern of UADT cancer might be
      present between the Western and Asian populations. We performed a pathology based
      statistical study on UADT cancers in Korean patients. Cases from Korea Cancer
      Center Hospital, from January 1, 1988 through December 31, 1998, were subjected
      to the study. Among 2,842 cases, epithelial malignancies accounted for 87.8%,
      with squamous cell carcinoma as the major type (76.5%). The larynx was the most
      commonly affected site (26%), followed by the oral cavity (25.1%), oropharynx
      (13%), nasopharynx (9%), hypopharynx (8.4%), paranasal sinuses (6.4%), nasal
      cavity (6%) and salivary glands (6.1%). The percentage of squamous cell carcinoma
      was highest (98.7%) at the hypopharynx, and lowest at the nasal cavity (42.3%),
      which showed the most diverse tumor entities. Korean patients with UADT cancers
      presented with a higher incidence of non-epidermoid malignancy including sarcoma
      (1.5%) and malignant melanoma (1.4%), and a higher frequency of involvement of
      the sinonasal tract, compared with the Western patients.

PMID- 11850584
TI  - Reduced E-cadherin expression as a cause of distinctive signet-ring cell variant
      in colorectal carcinoma.
AB  - Colorectal signet-ring cell carcinoma (SRCC) is a rare type of adenocarcinoma and
      presents with distinctive clinicopathological features. This study was performed
      to assess the biological characteristics of colorectal SRCC regarding the E
      cadherin expression. Seventeen patients with primary colorectal SRCC were
      identified and their clinicopathological characteristics were analyzed. The mean
      age of the 17 patients was 45.3 yr (14-68). Immunohistochemical staining of E
      cadherin and beta-catenin were performed in ten colorectal SRCCs and in 30
      ordinary colorectal adenocarcinomas as control. Primary colorectal SRCC occurred
      in 0.7% of 2,388 colorectal adenocarcinomas. Most patients had advanced stage
      tumor at surgery (stage III and IV, AJCC: 82%). Five-year survival rate was 16%.
      Peritoneal seeding was the most common recurrence pattern (41%) and liver
      metastasis was not identified. All SRCCs showed a markedly reduced or absent
      expression of E-cadherin on immunohistochemical staining, whereas seven (23.3%)
      of ordinary carcinomas showed reduced expression, thereby indicating a
      significant difference between the two groups (p<0.005). In immunohistochemical
      staining for beta-catenin, eight of ten SRCCs showed reduced membrane expression
      that did not attain statistical significance compared to ordinary
      adenocarcinomas. It is suggested that aberrant E-cadherin expression may explain
      the distinct clinicopathological features in primary colorectal SRCC.

PMID- 11850585
TI  - Coexpression of MUC1 with p53 or MUC2 correlates with lymph node metastasis in
      colorectal carcinomas.
AB  - The alteration of the mucin profile have been known to play a role in colorectal
      carcinogenesis. MUC1 is up-regulated and MUC2 is down-regulated in
      colorectalcarcinomas. Overexpression of p53 is frequently noted in colorectal
      carcinomas with deep invasion or lymph node metastasis. However, there have been
      few reports about the association between MUC1, MUC2, and p53 expression with
      respect to the metastatic potential. This study was aimed to investigate the
      relationship of MUC1, MUC2, and protein p53 expressions with clinicopathological
      factors in colorectal carcinomas. Expressions of MUC1, MUC2, and p53 protein were
      examined immunohistochemically. Of total 97 cancers, 44 (45%) were MUC1 positive,
      39 (40%) were MUC2 positive and 58 (59%) showed a p53 overexpression.
      Coexpression of MUC1 with p53 and dual expression of MUC1 with MUC2 were
      associated with a higher frequency of lymph node metastasis (p<0.05). The right
      colon showed a higher MUC1 positivity and frequent lymph node metastasis than the
      left colon (p<0.05). These results suggest that the coexpression of MUC 1 with
      p53 or MUC2 are involved in regional lymph node metastasis in colorectal
      carcinomas. The high expression of MUC1 in the right colon cancer was revealed to
      relate with lymph node metastasis.

PMID- 11850586
TI  - Insulin and glucagon secretions, and morphological change of pancreatic islets in
      OLETF rats, a model of type 2 diabetes mellitus.
AB  - This study was performed to observe the changes of glucose-related hormones and
      the morphological change including ultrastructure of the pancreatic islets in the
      male Otsuka Long-Evans Tokushima Fatty rat. Area under the curve (AUC) of glucose
      at the 30th (709 plus minus 73 mg.h/dL) and at the 40th week (746 plus minus 87
      mg.h/ dL) of age were significantly higher than that at the 10th week (360 plus
      minus 25 mg.h/ dL). AUC of insulin of the 10th week was 2.4 plus minus 0.9
      ng.h/mL, increased gradually to 10.8 plus minus 8.3 ng.h/mL at the 30th week, and
      decreased to 1.8 plus minus 1.2 ng.h/mL at the 40th week. The size of islet was
      increased at 20th week of age and the distribution of peripheral alpha cells and
      central beta cells at the 10th and 20th weeks was changed to a mixed pattern at
      the 40th week. On electron microscopic examination, beta cells at the 20th week
      showed many immature secretory granules, increased mitochondria, and
      hypertrophied Golgi complex and endoplasmic reticulum. At the 40th week, beta
      cell contained scanty intracellular organelles and secretory granules and
      apoptosis of acinar cell was observed. In conclusion, as diabetes progressed,
      increased secretion of insulin was accompanied by increases in size of islets and
      number of beta-cells in male OLETF rats showing obese type 2 diabetes. However,
      these compensatory changes could not overcome the requirement of insulin
      according to the continuous hyperglycemia after development of diabetes.

PMID- 11850587
TI  - FKBP-12 exhibits an inhibitory activity on calcium oxalate crystal growth in
      vitro.
AB  - Urolithiasis and calcium oxalate crystal deposition diseases are still
      significant medical problems. In the course of nephrocalcin cDNA cloning, we have
      identified FKBP-12 as an inhibitory molecule of calcium oxalate crystal growth.
      lambdagt 11 cDNA libraries were constructed from renal carcinoma tissues and
      screened for nephrocalcin cDNA clones using anti-nephrocalcin antibody as a
      probe. Clones expressing recombinant proteins, which appeared to be antigenically
      cross-reactive to nephrocalcin, were isolated and their DNA sequences and
      inhibitory activities on the calcium oxalate crystal growth were determined. One
      of the clone lambda gt 11 #31-1 had a partial fragment (80 bp) of FKBP-12 cDNA as
      an insert. Therefore, a full-length FKBP-12 cDNA was PCR-cloned from the lambda
      gt 11 renal carcinoma cDNA library and was subcloned into an expression vector.
      The resultant recombinant FKBP-12 exhibited an inhibitory activity on the calcium
      oxalate crystal growth (Kd=10(-7) M). Physiological effect of the extracellular
      FKBP-12 was investigated in terms of macrophage activation and proinflammatory
      cytokine gene induction. Extracellular FKBP-12 failed to activate macrophages
      even at high concentrations. FKBP-12 seems an anti-stone molecule for the oxalate
      crystal deposition disease and recurrent stone diseases.

PMID- 11850588
TI  - Cleft lip and palate incidence among the live births in the Republic of Korea.
AB  - We present an epidemiologic study of cleft lip and palate in the Republic of
      Korea from January 1, 1993 through December 31, 1993. In 1993, the number of
      total live births was 715,817. And from 1993 through 1995, a total of 1,293 new
      patients with cleft lip and palate who were born in 1993 were identified. The
      incidence of cleft lip and palate was 1.81 per 1000, that is, 1 per 554 live
      births. The cleft lip: cleft lip and palate: cleft palate alone ratio was
      1.13:1:1.19. The male: female ratio was 2.1:1 in the cleft lip group, and 2.5:1
      in the cleft lip and palate group. We could detect a male predominance in both
      groups. In contrast, the ratio was 0.95:1 in the cleft palate group. The left:
      right: bilateral ratio was 1.9:1:0.23 in cleft lip group, and the ratio was
      2.2:1:1.1 in the cleft lip and palate group. This is the first nation-wide study
      to provide detailed data on the incidence of cleft lip and palate in the live
      births in the Republic of Korea.

PMID- 11850589
TI  - Parental decisions of prenatally detected sex chromosome abnormality.
AB  - Because of the widespread use of amniocentesis, the prenatal recognition of sex
      chromosome abnormality (SCA) has become increasingly common. Recent literature
      provided an insight into the understanding of the natural history and prognosis
      for individuals with SCA. Our study was designed to review the parental decision
      on pregnancy with SCA. Over the last 10 yr, we diagnosed 38 cases (0.50%) with
      SCA out of 7,498 prenatal cases. We reviewed the records and the results of the
      pregnancies. We included the cases (n=25) of apparently normal anatomic fetus to
      analyze the factors influencing parental decision. We excluded 13 cases with
      obvious anomaly or presumably bad outcome. Fifteen (60%) couples continued their
      pregnancies and ten (40%) terminated theirs. Nine couples (64%) out of fourteen
      mosaicism cases continued their pregnancies. All five pregnancies assisted by
      reproductive technique continued their pregnancies. More pregnancies were
      continued when counseling was done by an MD geneticist rather than by an
      obstetrician. A significant trend was observed with a higher rate of pregnancy
      continuation in recent years. The genetic counseling is important to give
      appropriate information to the parents. Establishing guidelines and protocols
      will help both obstetricians and parents to make a decision.

PMID- 11850590
TI  - Donor specific response of estrogen and progesterone on cultured human
      melanocytes.
AB  - The mechanisms of estrogen and progesterone in human cutaneous pigmentation are
      largely unknown. The molecular identification of estrogen receptor (ER) and
      progesterone receptor (PR) in the human melanocytes is of great importance to
      understand the mechanisms. We performed immunocytochemistry analysis and
      demonstrated that ER and PR were expressed in the cytoplasms and nuclei of human
      melanocytes. Reverse transcriptase-polymerase chain reaction (RT-PCR) and
      sequence analysis confirmed the expression of ER and PR at the transcriptional
      level. Despite of the presence of ER and PR, the physiological and pregnant
      levels of estrogen and progesterone showed inconsistent effects on the
      proliferation and tyrosinase activity of cultured human melanocytes. These
      results suggest that human melanocytes express ER and PR, which have a donor
      specific action in human pigmentation. Further studies are needed to elucidate
      the induction mechanism and functions of these receptors, and the role of
      estrogen and progesterone in melanocytes.

PMID- 11850591
TI  - A cohort study on the association between psychotropics and hip fracture in
      Korean elderly women.
AB  - To test the hypothesis that the intake of psychotropics may increase the risk of
      hip fracture, a cohort study was conducted upon elderly Korean women. The Korean
      Elderly Pharmacoepidemiology Cohort was constructed from members of the Korea
      Medical Insurance Corporation over 65 yr of age who were living in Busan
      Metropolitan City in 1993. Study participants (n=6,043) were female respondents
      to a self-administered question survey. Information on the intake of
      psychotropics was obtained from the drug prescription database, which contained
      all psychotropic prescriptions during any hospital admission over the two-year
      period between January 1, 1993 and December 31, 1994. The cohort follow-up has
      been conducted with information on hip fracture being collected from the Korea
      Medical Insurance Corporation medical treatment claims database over the four
      year period between January 1, 1993 and December 31, 1996. Three hundred and
      three subjects had received 745 psychotropics prescriptions and 56 cases of hip
      fracture were found. After adjusting for age, body mass index, and drinking
      history, it was found that the intake of psychotropics significantly increased
      the risk of hip fracture (adjusted odds ratio, 4.24; 95% confidence interval,
      1.89-9.52). This study suggests that the intake of psychotropics might be an
      important risk factor for hip fracture in elderly Korean women.

PMID- 11850592
TI  - Undifferentiated spondyloarthropathy in Korea: focusing on peripheral arthritis.
AB  - Undifferentiated spondyloarthropathy (USpA) includes the forms that do not meet
      criteria for the established categories of spondyloarthropathy. The clinical
      spectrum of USpA is therefore wide and few studies have been published on USpA,
      especially peripheral arthritis. A total of 107 patients fulfilling the European
      Spondyloarthropathy Study Group criteria for SpA were studied retrospectively by
      a chart review and interview by a rheumatologist. Peripheral arthritis, excluding
      hip and shoulder involvement, occurred in 97 of the 107 patients (91%). Joint
      involvement tended to be monoarticular or pauciarticular, and most frequently
      developed in peripheral joints including the knee and ankle. Among the 97
      patients with peripheral arthritis, only 37 (35%) had a persistent arthritis. HLA
      B27 was detected in 80 patients (78%). Peripheral arthritis was found in the
      lower extremities regardless of symmetry or asymmetry and tended to run a benign
      course with only a few patients having persistent arthritis.

PMID- 11850593
TI  - Association Between FcgammaR IIa and IIIa polymorphism and clinical
      manifestations in Korean patients with adult-onset Still's disease.
AB  - High-dose intravenous immunoglobulins alter the disease activity of adult-onset
      Still's disease (AOSD). Because activation status of FcgammaR is possibly
      dependent on their genetic polymorphisms, we investigated whether the
      polymorphisms of FcgammaR IIa and IIIa are risk factors, and affect the clinical
      features of AOSD. Genomic DNA was extracted from 36 patients and from 197 healthy
      controls. Polymerase chain reaction for FcgammaR IIa and IIIa using the allele
      specific primers and direct sequencing of FcgammaR IIIa polymorphic site were
      performed. The frequencies of FcgammaR IIa/IIIa genotype between patients with
      AOSD and controls were not different. The allelic frequencies of FcgammaR
      IIa/IIIa between patients with AOSD and controls were not different, either.
      However, the FcgammaR IIa-R/R131 genotype was associated with a higher
      concentration of hemoglobin (p=0.04) and stable liver function (p=0.009) than the
      other genotypes. The FcgammaR IIIa-F/F176 genotype was associated with
      significantly lower titers of serum ferritin (p=0.025), and higher serum albumin
      (p=0.037) and cholesterol (p=0.014) concentrations than the other genotypes. This
      study suggest that the FcgammaR IIa and IIIa polymorphisms might not be genetic
      risk factors for AOSD in Korean, but contribute to the activity of disease.
      FcgammaR IIa-R/R131 and IIIa-F/F176 genotypes, low-binding genotypes for IgG2a
      and G1, may have more protective effects in acute stage of the disease than the
      other genotypes.

PMID- 11850594
TI  - Effects of different concentrations of formalin on paw edema and pain behaviors
      in rats.
AB  - The aim of this study was to determine whether formalin reliably provokes a paw
      edema and pain behavior. The paw of male Sprague-Dawley rats were injected with
      100 microliter of formalin with 2.5% (F2.5), 5% (F5), and 10% (F10)
      concentrations. Following the formalin (n=8) or saline (control, n=6) injection,
      the flinching or licking of the paw was recorded for the phase 1 response (0-5
      min after injection) and phase 2 response (20-60 min). The formalin-induced paw
      edema was assessed by measuring the diameters of the injected paws at 4 hr after
      injection. As for flinching, phase 1 and 2 of all three groups showed higher
      frequency than those of the control group (p<0.05). As for licking, phase 1
      cumulative time of the F2.5 and F10 groups, and phase 2 cumulative time of the
      F2.5 and F5 groups showed a longer duration than those in the control group
      (p<0.05). The diameters of the paw in the F10 group were significantly larger
      than those in the control group (p<0.05). Flinching behavior was more reliably
      expressed the biphasic response than licking response at all formalin
      concentrations. Peak of the licking was reached at 2.5% and that of flinching was
      reached at 5%, whereas the paw edema peaked at 10% concentration. This suggests
      that there may be some dissociation of nociception from the edema formation.

PMID- 11850595
TI  - The prevalence of mental retardation among third grade elementary school children
      in the Suwon area, Korea.
AB  - The purpose of this study was to estimate the prevalence of mental retardation
      (MR) in Korea. The study population comprised 1,757 third-grade elementary school
      children residing in a single school district in Suwon, Korea. We conducted the
      total population survey for 1,537 children who attended one of 5 schools in the
      district. For the remaining 220 children who did not attend a school in the
      school district, we found children with MR via inspection of the register list of
      the disabled. A total of 16 children (7 of the 1,537 children and 9 of the 220
      children) were found to have MR, yielding a prevalence of MR of 9.1/1,000.
      Considering that about 60% of the people with disabilities are registered in
      Korea, there would be at least 6 unregistered children with MR among the 220
      children, so that the prevalence of MR can be estimated at 12.5/1,000 for the
      Suwon area.

PMID- 11850596
TI  - Hanja alexia with agraphia after left posterior inferior temporal lobe
      infarction: a case study.
AB  - Korean written language is composed of ideogram (Hanja) and phonogram (Hangul),
      as Japanese consists of Kanji (ideogram) and Kana (phonogram). Dissociation
      between ideogram and phonogram impairment after brain injury has been reported in
      Japanese, but few in Korean. We report a 64-yr-old right-handed man who showed
      alexia with agraphia in Hanja but preserved Hangul reading and writing after a
      left posterior inferior temporal lobe infarction. Interestingly, the patient was
      an expert in Hanja; he had been a Hanja calligrapher over 40 yr. However, when
      presented with 65 basic Chinese letters that are taught in elementary school, his
      responses were slow both in reading (6.3 sec/letter) and writing (8.8
      sec/letter). The rate of correct response was 81.5% (53 out of 65 letters) both
      in reading and writing. The patient's performances were beyond mean-2SD of those
      of six age-, sex-, and education-matched controls who correctly read 64.7 out of
      65 and wrote 62.5 out of 65 letters with a much shorter reaction time (1.3
      sec/letter for reading and 4.0 sec/letter for writing). These findings support
      the notion that ideogram and phonogram can be mediated in different brain regions
      and Hanja alexia with agraphia in Korean patients can be associated with a left
      posterior inferior temporal lesion.

PMID- 11850597
TI  - Change of hyperexcitability of hippocampus by cyclosporin A and its modulatory
      action by fentanyl.
AB  - Cyclosporin A is used to treat patients with immune-mediated diseases, chronic
      diseases requiring organ transplantation, or malignancies. These conditions often
      require higher cyclosporin A doses, which may be toxic to the central nervous
      system. Fentanyl is also used in clinical conditions that have a risk of hypoxic
      neurosusceptibility, which suggests that the drug may be a neuroprotective
      agonist against brain ischemic injury. Fentanyl is an opioid agonist and appears
      to play an important role in regulating the excitability of the hippocampus under
      electroconvulsion. In this study, the effects of fentanyl on modulating
      cyclosporin A-induced neurotoxicity was investigated. Treatment with 3 micrometer
      of cyclosporin A was found to reduce the electroconvulsive activity threshold.
      Fifty ng/mL of fentanyl reduced the electroconvulsive activity, and 1 micrometer
      of DAGO ([D-Ala2, N-Me-Phe4, Gly-ol]-enkephalin) also decreased the
      electroconvulsive activity. Fifty ng/mL of fentanyl was also found to reduce
      cyclosporin A-induced electroconvulsive activity. Although cyclosporin A
      neurotoxicity may be observed in various conditions, the opioid effect of
      neuroprotection may be involved in an interrelated mechanism. The exogenous
      opioid agonist suppressed cyclosporin A-induced electroconvulsive activity.
      Furthermore, there may be a functional anticonvulsant effect on cyclosporin A
      induced neurotoxicity with an increased opioid agonist concentration.

PMID- 11850598
TI  - Histochemical and molecular genetic study of MELAS and MERRF in Korean patients.
AB  - Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episode
      (MELAS) and myoclonic epilepsy and ragged-red fibers (MERRF) are rare disorders
      caused by point mutation of the tRNA gene of the mitochondrial genome. To
      understand the pathogenetic mechanism of MELAS and MERRF, we studied four
      patients. Serially sectioned frozen muscle specimens with a battery of
      histochemical stains were reviewed under light microscope and ultrastructural
      changes were observed under electron microscope. The polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) analysis was performed and
      the tRNA genes were sequenced to confirm mutations. In two patients with MELAS,
      strongly succinyl dehydrogenase positive blood vessels (SSVs) and many cytochrome
      oxidase (COX) positive ragged-red fibers (RRFs) were observed, and A3243G
      mutations were found from the muscle samples. In two patients with MERRF, neither
      SSV nor COX positive RRFs were seen and A8344G mutations were found from both
      muscle and blood samples. In the two MERRF families, the identical mutation was
      observed among family members. The failure to detect the mutation in blood
      samples of the MELAS suggests a low mutant load in blood cells. The histochemical
      methods including COX stain are useful for the confirmation and differentiation
      of mitochondrial diseases. Also, molecular biological study using muscle sample
      seems essential for the confirmation of the mtDNA mutation.

PMID- 11850599
TI  - Penicillin-resistant Aerococcus viridans bacteremia associated with
      granulocytopenia.
AB  - Aerococcus viridans, a catalase-negative gram-positive coccus rarely causing
      bacteremia, was isolated from blood cultures of a 52-yr-old man under the
      granulocytopenic condition. The isolate showed the typical characteristics of A.
      viridans, i.e., tetrad arrangements in gram stain, positive pyrrolidonyl
      aminopeptidase (PYR) and negative leucine aminopeptidase (LAP) reactions, and no
      growth at 45 degrees C. The isolate was revealed to be highly resistant to
      penicillin, erythromycin, clindamycin, and ceftriaxone, although most strains of
      A. viridans isolated from the previously reported patients were susceptible to
      penicillin and other commonly used antibiotics. Even though A. viridans is rarely
      associated with human infections, it could be a potential causative agent of
      bacteremia, especially in immunocompromised patients.

PMID- 11850601
TI  - Primary vesical actinomycosis: a case diagnosed by multiple transabdominal needle
      biopsies.
AB  - Primary vesical actinomycosis is an extremely rare disease. In most cases it is
      misdiagnosed as vesical or urachal tumor and usually diagnosed through post
      operative pathologic confirmation. Here we report a case of primary vesical
      actinomycosis confirmed by preoperative repeated multiple transabdominal
      biopsies. The patient was a 49-yr-old woman who presented with frequency,
      dysuria, and intermittent gross hematuria for 2 months. Computed tomography and
      cystoscopic examination showed broad-based, edematous, and protruding mass at the
      dome and anterior portion of the bladder. The clinical and imaging findings of
      the patient initially suggested vesical malignancy. Transurethral resection and
      multiple biopsies of the mass were performed. Pathologic examination demonstrated
      fibrosis with chronic inflammation. We performed repeated transabdominal multiple
      needle biopsies for further pathologic confirmation. Histopathologic examination
      demonstrated typical sulfur granules, which were consistent with actinomycosis.

PMID- 11850600
TI  - X-linked hyper-IgM syndrome associated with Cryptosporidium parvum and
      Cryptococcus neoformans infections: the first case with molecular diagnosis in
      Korea.
AB  - X-linked hyper-IgM syndrome (XHIM) is a rare primary immunodeficiency disorder,
      caused by mutations of the gene encoding CD40 ligand (CD40L; CD154). We report
      the clinical manifestations and mutational analysis of the CD40L gene observed in
      a male patient from a XHIM family. Having hypogammaglobulinemia and elevated IgM,
      the 3-yr-old boy exhibited the characteristic clinical features of XHIM. The
      patient suffered from frequent respiratory infections, and chronic enteritis
      caused by Cryptosporidium parvum. In addition, a lymph node biopsy and a culture
      from this sample revealed C. neoformans infection. Activated lymphocytes from the
      patient failed to express CD40L on their surface as assessed by flow cytometry
      and a missence mutation (W140R) was found at the XHIM hotspot in his CD40L cDNA
      to confirm the diagnosis. Genetic analysis of the mother and sister showed a
      heterozygote pattern, indicating carrier status. To our knowledge, this is the
      first report on the molecular diagnosis of an XHIM patient in Korea.

PMID- 11850602
TI  - Prenatal diagnosis of tetralogy of Fallot associated with chromosome 22q11
      deletion.
AB  - Microdeletion of 22q11 is responsible for DiGeorge syndrome, velocardiofacial
      syndrome, congenital conotruncal heart defects, and related disorders. We report
      our experiences on prenatal diagnosis by fluorescence in situ hybridization
      (FISH) for 22q11 deletion in two fetuses with tetralogy of Fallot. Karyotyping
      and FISH of the parents revealed that one fetus inherited the disease from
      maternal microdeletion. These findings suggest the importance of performing FISH
      in pregnancies with prenatally detected tetralogy of Fallot.

PMID- 11850603
TI  - Autologous stem cell transplantation in the treatment of refractory rheumatoid
      arthritis.
AB  - The concept of using high-dose immunosuppressive treatment (HDIT) with autologous
      stem cell transplantation (ASCT) to treat patients with refractory rheumatoid
      arthritis has been provided by animal studies and anecdotal case reports. Over
      the past five years, an increasing number of patients with refractory rheumatoid
      arthritis have received HDIT with ASCT as an adjunct to intense
      immunosuppression. Here, we present a case of refractory rheumatoid arthritis in
      a 54-yr-old woman using HDIT with ASCT. Peripheral blood stem cells were
      mobilized with cyclophosphamide (4 g/m(2)) followed by G-CSF (5 microg/kg/day).
      Leukapheresis continued daily until the number of harvested progenitor cells
      reached 2 x 10(6) CD34+ cells/kg after CliniMax CD34+ positive selection. For
      HDIT, high-dose cyclophosphamide (total dose 200 mg/kg) and antithymocyte
      globulin (total dose 90 mg/kg) were administered and CD34+ cells were infused 24
      hr after HDIT. The patient tolerated the treatment well but experienced an
      episode of neutropenic fever. She achieved an early dramatic improvement of joint
      symptoms during therapy. Fifty percent of improvement of rheumatoid arthritis by
      the American College of Rheumatology (ACR 50) preliminary definition was
      fulfilled during the 6 months following ASCT. Although further long-term follow
      up is required, the patient's activity of arthritis has been stable since
      receiving HDIT with ASCT.

PMID- 11850604
TI  - Development of multiple pigmented nevi within segmental nevus depigmentosus.
AB  - Nevus depigmentosus is a stable and well-circumscribed congenital hypomelanosis
      that may be in an isolated, dermatomal or systemic form. An 18-yr-old Korean man
      with segmental nevus depigmentosus developed multiple pigmented nevi which were
      present only within the confines of the leukoderma. Histologic and electron
      microscopic studies rendered a diagnosis of nevus depigmentosus with dysplastic
      nevus to the patient. The genetic alteration of melanocytes in the hypopigmented
      lesion is assumed to have resulted in the development of multiple pigmented nevi.

PMID- 11850605
TI  - Trilateral retinoblastoma: a case report.
AB  - Trilateral retinoblastoma is a rare, but well recognized syndrome. These tumors
      usually occur in the pineal, parasellar, or suprasellar regions several years
      after successful management of ocular retinoblastomas without evidence of direct
      extension or distant metastasis. Here we report a case of trilateral
      retinoblastoma presenting initially with a sellar tumor and with concurrent
      unilateral retinoblastoma. The patient was a 5-month-old baby girl showing poor
      eye contact and nystagmus for several days. She had no family history of
      retinoblastoma. Brain MRI revealed a midline suprasellar tumor without evidence
      of cerebrospinal fluid seeding or extracranial metastasis. A pathologic diagnosis
      of retinoblastoma was made for her brain tumor, and a small, intraocular
      retinoblastoma was detected in the left eye by thorough examination of the
      fundus. If a retinoblastoma occurs in the midline of the brain, including the
      pineal and sellar regions, a careful screening to detect any additional retinal
      tumors should be performed. Moreover, since these tumors are often hereditary and
      harbor a worse prognosis, the diagnosis has implications for genetic counseling.
      This is the first report on a case of trilateral retinoblastoma in Korea
      presented with a sellar mass.

PMID- 11850606
TI  - A case of polymyositis with dilated cardiomyopathy associated with interferon
      alpha treatment for hepatitis B.
AB  - Polymyositis is a rare complication of interferon alpha treatment as a result of
      immune-modulating role of the drug itself. In this case, interferon alpha induced
      polymyositis and cardiomyopathy is diagnosed in a 33-yr-old male patient with
      history of chronic hepatitis B. To treat hepatitis B, interferon alpha was
      administered until the proximal muscle weakness developed. Thereafter, sixteen
      cycles of immunoglobulin treatment (400 mg/kg) along with corticosteroids were
      instituted and led to an improvement in subjective symptoms with decreases in
      level of CPK and LDH. However, dilated cardiomyopathy has not improved in spite
      of the cessation of interferon treatment. Unlike the persistently elevated serum
      HBV DNA level, the serum ALT and AST levels have gradually decreased. Our case
      shows that clinical symptoms of polymyositis improved with steroid and
      immunoglobulin treatment without deterioration of the hepatitis B. To our
      knowledge, this is the first case of polymyositis associated with dilated
      cardiomyopathy after the administration of interferon in a patient with hepatitis
      B.

PMID- 11850607
TI  - Simultaneous occurrence of subarachnoid hemorrhage due to ruptured aneurysm and
      remote hypertensive intracerebral hemorrhage: case report.
AB  - Simultaneous occurrence of aneurysmal subarachnoid hemorrhage (SAH) and
      hypertensive intracerebral hemorrhage (ICH) is very rare and only two cases have
      been previously reported in the literatures. We present a case of 68-yr-old man
      with a history of untreated hypertension, who suffered from sudden onset of
      headache followed by right hemiparesis. Computed tomographic (CT) scan revealed
      SAH in the basal cistern and remote ICH at the left putamen. Cerebral angiography
      showed a saccular aneurysm at the anterior communicating artery. No other
      vascular anomaly could be found at left putaminal area. Nine days after the ictal
      attack of SAH, the neck of aneurysm was clipped via the left frontotemporal
      craniotomy. Because of the ICH at the left frontal lobe and intraventricular
      hematoma on postoperative CT, we performed hematoma removal and external
      ventricular drainage 3 hours after the first operation. Postoperative
      neurological status had been improved to be drowsy and he was discharged in a
      severely disabled state 4 weeks after surgery. We suggest that the rupture of
      aneurysm possibly caused a rapid increase in blood pressure and subsequently
      resulted in hypertensive ICH.

PMID- 11850608
TI  - Intrasellar schwannoma mimicking pituitary adenoma: a case report.
AB  - Intrasellar location of schwannoma is extremely rare, although intracranial
      schwannomas account for up to 8% of all primary brain tumors. An unusual case of
      an intrasellar schwannoma radiographically and clinically simulating a pituitary
      adenoma is reported. A 39-yr-old man presented a 10-month history of visual
      disturbance and decreased libido. Neurological examination showed poor visual
      acuity of both eyes with bitemporal hemianopsia. Computed tomography and magnetic
      resonance imaging showed a sellar tumor with suprasellar extension. Pituitary
      adenoma was considered as a preoperative diagnosis. The tumor was removed through
      a trans-sphenoidal approach. Microscopic examination of the tumor revealed
      schwannoma.

PMID- 11850609
TI  - [Simplified prognostic test in the early detection of acute pancreatitis].
AB  - BACKGROUND: Even though the diagnosis of acute pancreatitis has become easier by
      the measurement of specific pancreatic enzymes, early assessment of the prognosis
      still remains a clinical challenge at an early stage of the disease. The imaging
      procedures and the elevated mediators, are not widely available at the beginning.
      The aim of this study is to analyze the blood concentration of lipase, glucose,
      calcium and leucocytes (Simplified Prognostic Test). The values of these markers
      in the prognostic evaluation of acute pancreatitis are described. METHODS: A
      total of 45 patients with acute pancreatitis were evaluated; 38 patients
      developed a mild acute pancreatitis and 7 patients developed a severe acute
      pancreatitis. The values of serum markers at cut-offs of 160 mg/100 ml for
      glucose, 10.000 U/L for lipase, 13.000 leucocytes/100 ml and 8.5 mg/ml for
      calcium were monitored. RESULTS: On admission to hospital, concentration of
      glucose, lipase, calcium and leucocytes were significantly higher in the second
      group (severe acute pancreatitis) than in the first one (p<0.01 for glucose,
      leucocytes and calcium; p<0.05 for lipase). The test was considered positive if 3
      out of 4 markers were significant. CONCLUSIONS: At an early stage the SPT was
      positive in patients who developed severe disease. SPT had sensitivity of 71.4%
      and specificity of 75.5%. The preliminary results indicate that there is no
      significant difference between the Ranson score and SPT in evaluating acute
      pancreatitis. SPT is simple and quick to perform and unlike the recently
      introduced laboratory markers can easily be adopted in emergency clinical
      practice. Definite proof may however only be obtained by a prospective,
      randomized clinical trial.

PMID- 11850610
TI  - How to decrease the non-compliance in a clinical trial.
AB  - BACKGROUND: A high compliance is an important scientific objective for a
      multicenter clinical trial and also an ethical responsibility. Some of non
      compliance causes can be prevented during the enrollment phase by an accurate
      selection of subjects (quality of recruitment), other can be controlled after the
      recruitment, by a good organization of follow-up tests and visits (quality of
      organization). METHODS: The policy adopted in the Operative Center of the
      Delegazione Alto Lario della Lega Italiana per la Lotta contro i Tumori di
      Gravedona (Como) for obtaining a high compliance of women recruited in the
      Italian Tamoxifen Prevention Study are illustrated. RESULTS: The non-compliance
      rate of this center is low: 5.6 vs 23.3% of the whole Italian trial. CONCLUSIONS:
      The low non-compliance demonstrates the efficacy of the policy adopted.

PMID- 11850612
TI  - [Adult onset Still's disease].
AB  - Adult onset Still's disease (AOSD), the adult variant of the systemic form of the
      juvenile rheumatoid arthritis, is an uncommon disorder of unknown origin.
      Although the pathogenesis has not yet been clarified, an immunologically mediated
      inflammation occurs in active AOSD. High spiking fever, evanescent maculo-papular
      skin rash, arthralgias/arthritis, neutrophilic leukocytosis, negative rheumatoid
      factor and antinuclear antibodies, as well as a marked hyperferritinemia are the
      major features of AOSD. Sore throat, lymphadenopathies, hepato-splenomegaly,
      abdominal pain, polyserositis, respiratory distress syndrome, multiple organ
      dysfunction and disseminated intravascular coagulation may also occur. The
      clinical course of AOSD is extremely variable and unpredictable and can be
      divided into three main patterns: a self-limited or monocyclic pattern, a
      polycyclic or intermittent course, with one or more flares of the disease and
      complete remission among the episodes, and a chronic course, characterized by
      persistently active disease, usually due to a chronic, destructive arthritis.
      Since there are not pathognomonic laboratory parameters or histological findings,
      the diagnosis of AOSD requires the exclusion of infectious, malignant and
      autoimmune disorders. Some sets of criteria for classification have been
      proposed, but so far not validated. The prognosis of AOSD is usually considered
      relatively benign, although a destructive arthritis may cause severe disability
      and the multisystemic life-threatening complications of the disease may determine
      a fatal outcome. Treatment usually consists in nonsteroidal anti-inflammatory
      drugs and corticosteroids, but a more aggressive approach with disease modifying
      antirheumatic or immunosuppressive drugs may be required.

PMID- 11850613
TI  - Mitochondrial uncoupling proteins in human physiology and disease.
AB  - Uncoupling proteins are mitochondrial carrier proteins that catalyse a regulated
      proton leak across the inner mitochondrial membrane, diverting free energy from
      ATP synthesis by the mitochondrial F0F1-ATP synthase to the production of heat.
      Uncoupling protein 1 (UCP1), which is exclusively expressed in brown adipose
      tissue, is the mediator of thermogenesis in response to beta-adrenergic
      stimulation. Using gene a knockout mouse model, UCP1 has been shown to be
      required for cold acclimation. Two homologues of UCP1, UCP2 and UCP3, have been
      identified recently and show a much wider tissue distribution. UCP2 and UCP3 have
      been postulated to play a role in the regulation of cold acclimation, energy
      expenditure and diet-induced thermogenesis in humans, who, in contrast to
      rodents, have very little brown fat in adult life. However, evidence is
      accumulating that thermogenesis and regulation of body weight may not be the
      physiological functions of UCP2 and UCP3. For instance, mice deficient for UCP2
      or UCP3 are not cold-intolerant and do not develop obesity. Alternative functions
      were suggested, primarily based on findings in UCP2 and UCP3 gene knockout mice.
      Both UCP2- and UCP3-deficient mice were found to overproduce reactive oxygen
      species and UCP2-deficient mice to hypersecrete insulin. Thus, the UCP1
      homologues may play a role in regulating mitochondrial production of reactive
      oxygen species and b-cell function. In this review, we discuss the role of UCP1,
      UCP2 and UCP3 in human physiology and disease, primarily based on findings from
      the various animal models that have been generated.

PMID- 11850611
TI  - The use of antithrombotic drugs in older people.
AB  - Older individuals (subjects aged >65 years) largely contribute to the percentage
      deaths due to myocardial infarction (MI) and stroke. The incidence of venous
      thromboembolism (VTE) is also higher >65 years old patients. However, the risk of
      bleeding complications in patients on antithrombotic drugs increases with age and
      with clinical conditions, as cognitive/psychiatric diseases, traumas,
      hypertension, poor compliance with medications, common in the elderly. Thus the
      risk-benefit ratio of antithrombotics should be carefully evaluated in older
      individuals. To prevent the risk and the recurrence of ischemic stroke and MI in
      the older patients with stable/ unstable angina, MI, TIA/stroke or peripheral
      arterial disease, antiplatelet drugs are of choice. Aspirin is the most widely
      used antiplatelet drug. Clopidogrel is safer and more effective than aspirin in
      this respect. The combination of heparin and aspirin is the treatment of choice
      for unstable angina and non-Q wave MI, also in the elderly. Low molecular weight
      heparins (LMWHs) proved to be as effective as standard heparin in this
      indication. In the absence of contraindications, thrombolysis for treatment of
      acute MI may be considered in the elderly. For the treatment of acute venous
      thromboembolism (VTE), intravenous standard heparin, subcutaneous standard
      heparin or LMWHs are effective. Because of the limited risk/benefit ratio,
      thrombolytic agents are not recommended for treating deep vein thrombosis (DVT)
      in the elderly. They should be limited to young patients and to patients with
      massive pulmonary embolism (PE). For chronic treatment of VTE, warfarin is the
      treatment of choice (INR 2.0-3.0), also in the elderly. Because of
      hypersensitivity to oral anticoagulants, lower dosages of warfarin are needed in
      the old patient. As to prophylaxis of VTE in surgery, in subjects at low-moderate
      risk, or in medical patients, low-dose heparin or low-dose LMWHs are effective.
      As to prophylaxis of VTE in surgery in subjects at high risk, adjusted-dose
      heparin or high-dose LMWHs are recommended. Finally, as to prevention of stroke
      in patients older than 75 with atrial fibrillation (AF), warfarin is of choice.

PMID- 11850615
TI  - [Usefulness of ultrasonography in the study of superficial lymph nodes. A case of
      cat scratch disease].
AB  - Ultrasonography is a wide spread, non-invasive and repeatable imaging
      methodology. It is able to evidence any type of lesion and to describe its
      extent, its site and its content. The ultrasound role in the diagnosis of a case
      of cat scratch disease in a 44 year old man is described. Symptoms included
      intermittent fever, pain and palpable tumefactions in right armpit and elbow. The
      patient underwent routine and lymphoadenopathy specific laboratory data.
      Ultrasound examination and echo-guided fine-needle biopsy of the evident lesions
      were performed. These exams, related to pathological clinical presentation, have
      shown a chronic granulomatous lymphadenopathy like cat scratch disease. This case
      provides further evidence that ultrasound procedures might play an important role
      in differential diagnosis of palpable lesions.

PMID- 11850614
TI  - [Transmissible spongiform encephalopathies. History, epidemiology, etiological,
      hyphotheses].
AB  - The history of transmissible spongiform encephalopathies is shortly reviewed
      beginning with the Westminster parliament act in the year 1755 up to the
      description in 1996 of the variant of the Creutzfeldt-Jakob disease, transmitted
      from cattle to man by alimentary route. The epidemiological patterns of
      encephalopathies of the various animal species and of the four encephalopathies
      up to date reported in man are shortly described: Creutzfeldt-Jakob disease,
      Kuru, Gerstmann-Straussler-Scheinker disease, Fatal Familial Insomnia.
      Etiological hypotheses are discussed until the identification of Prions: PrPcell,
      on the surface of normal cells, PrPscr in the brain of humans and animals dead
      for these diseases. The strains of the PrPscr are described on the basis of some
      characters observed through the passages in rodents and of molecular pattern. The
      possible future epidemiological evolution of the vCJD is also discussed.

PMID- 11850616
TI  - Sjogren's syndrome, hypersensitivity and HLA alleles.

PMID- 11850617
TI  - CEACAM1 regulates insulin clearance in liver.
AB  - We hypothesized that insulin stimulates phosphorylation of CEACAM1 which in turn
      leads to upregulation of receptor-mediated insulin endocytosis and degradation in
      the hepatocyte. We have generated transgenic mice over-expressing in liver a
      dominant-negative, phosphorylation-defective S503A-CEACAM1 mutant. Supporting our
      hypothesis, we found that S503A-CEACAM1 transgenic mice developed
      hyperinsulinemia resulting from impaired insulin clearance. The hyperinsulinemia
      caused secondary insulin resistance with impaired glucose tolerance and random,
      but not fasting, hyperglycemia. Transgenic mice developed visceral adiposity with
      increased amounts of plasma free fatty acids and plasma and hepatic
      triglycerides. These findings suggest a mechanism through which insulin signaling
      regulates insulin sensitivity by modulating hepatic insulin clearance.

PMID- 11850618
TI  - Dominant and recessive deafness caused by mutations of a novel gene, TMC1,
      required for cochlear hair-cell function.
AB  - Positional cloning of hereditary deafness genes is a direct approach to identify
      molecules and mechanisms underlying auditory function. Here we report a locus for
      dominant deafness, DFNA36, which maps to human chromosome 9q13-21 in a region
      overlapping the DFNB7/B11 locus for recessive deafness. We identified eight
      mutations in a new gene, transmembrane cochlear-expressed gene 1 (TMC1), in a
      DFNA36 family and eleven DFNB7/B11 families. We detected a 1.6-kb genomic
      deletion encompassing exon 14 of Tmc1 in the recessive deafness (dn) mouse
      mutant, which lacks auditory responses and has hair-cell degeneration. TMC1 and
      TMC2 on chromosome 20p13 are members of a gene family predicted to encode
      transmembrane proteins. Tmc1 mRNA is expressed in hair cells of the postnatal
      mouse cochlea and vestibular end organs and is required for normal function of
      cochlear hair cells.

PMID- 11850619
TI  - Higher-order structure in pericentric heterochromatin involves a distinct pattern
      of histone modification and an RNA component.
AB  - Post-translational modification of histone tails is thought to modulate higher
      order chromatin structure. Combinations of modifications including acetylation,
      phosphorylation and methylation have been proposed to provide marks recognized by
      specific proteins. This is exemplified, in both mammalian cells and fission
      yeast, by transcriptionally silent constitutive pericentric heterochromatin. Such
      heterochromatin contains histones that are generally hypoacetylated and
      methylated by Suv39h methyltransferases at lysine 9 of histone H3 (H3-K9). Each
      of these modification states has been implicated in the maintenance of HP1
      protein-binding at pericentric heterochromatin, in transcriptional silencing and
      in centromere function. In particular, H3-K9 methylation is thought to provide a
      marking system for the establishment and maintenance of stably repressed regions
      and heterochromatin subdomains. To address the question of how these two types of
      modifications, as well as other unidentified parameters, function to maintain
      pericentric heterochromatin, we used a combination of histone deacetylase
      inhibitors, RNAse treatments and an antibody raised against methylated branched
      H3-K9 peptides. Our results show that both H3-K9 acetylation and methylation can
      occur on independent sets of H3 molecules in pericentric heterochromatin. In
      addition, we identify an RNA- and histone modification-dependent structure that
      brings methylated H3-K9 tails together in a specific configuration required for
      the accumulation of HP1 proteins in these domains.

PMID- 11850620
TI  - A mutant PTH/PTHrP type I receptor in enchondromatosis.
AB  - Enchondromas are common benign cartilage tumors of bone. They can occur as
      solitary lesions or as multiple lesions in enchondromatosis (Ollier and Maffucci
      diseases). Clinical problems caused by enchondromas include skeletal deformity
      and the potential for malignant change to chondrosarcoma. The extent of skeletal
      involvement is variable in enchondromatosis and may include dysplasia that is not
      directly attributable to enchondromas. Enchondromatosis is rare, obvious
      inheritance of the condition is unusual and no candidate loci have been
      identified. Enchondromas are usually in close proximity to, or in continuity
      with, growth-plate cartilage. Consequently, they may result from abnormal
      regulation of proliferation and terminal differentiation of chondrocytes in the
      adjoining growth plate. In normal growth plates, differentiation of proliferative
      chondrocytes to post-mitotic hypertrophic chondrocytes is regulated in part by a
      tightly coupled signaling relay involving parathyroid hormone related protein
      (PTHrP) and Indian hedgehog (IHH). PTHrP delays the hypertrophic differentiation
      of proliferating chondrocytes, whereas IHH promotes chondrocyte proliferation. We
      identified a mutant PTH/PTHrP type I receptor (PTHR1) in human enchondromatosis
      that signals abnormally in vitro and causes enchondroma-like lesions in
      transgenic mice. The mutant receptor constitutively activates Hedgehog signaling,
      and excessive Hedgehog signaling is sufficient to cause formation of enchondroma
      like lesions.

PMID- 11850621
TI  - The DNA damage-dependent intra-S phase checkpoint is regulated by parallel
      pathways.
AB  - To preserve genetic integrity, mammalian cells exposed to ionizing radiation
      activate the ATM kinase, which initiates a complex response-including the S-phase
      checkpoint pathways-to delay DNA replication. Defects in ATM or its substrates
      Nbs1 or Chk2 (ref. 3), the Nbs1-interacting Mre11 protein, or the Chk2-regulated
      Cdc25A-Cdk2 cascade all cause radio-resistant DNA synthesis (RDS). It is unknown,
      however, whether these proteins operate in a common signaling cascade. Here we
      show that experimental blockade of either the Nbs1-Mre11 function or the Chk2
      triggered events leads to a partial RDS phenotype in human cells. In contrast,
      concomitant interference with Nbs1-Mre11 and the Chk2-Cdc25A-Cdk2 pathways
      entirely abolishes inhibition of DNA synthesis induced by ionizing radiation,
      resulting in complete RDS analogous to that caused by defective ATM. In addition,
      Cdk2-dependent loading of Cdc45 onto replication origins, a prerequisite for
      recruitment of DNA polymerase, was prevented upon irradiation of normal or
      Nbs1/Mre11-defective cells but not cells with defective ATM. We conclude that in
      response to ionizing radiation, phosphorylations of Nbs1 and Chk2 by ATM trigger
      two parallel branches of the DNA damage-dependent S-phase checkpoint that
      cooperate by inhibiting distinct steps of DNA replication.

PMID- 11850622
TI  - A gene-driven approach to the identification of ENU mutants in the mouse.
AB  - The construction of parallel archives of DNA and sperm from mice mutagenized with
      ethylnitrosurea (ENU) represents a potentially powerful and rapid approach for
      identifying point mutations in any gene in the mouse genome. We provide support
      for this approach and report the identification of mutations in the gene (Gjb2)
      encoding connexin 26, using archives established from the UK ENU mutagenesis
      program.

PMID- 11850623
TI  - Beethoven, a mouse model for dominant, progressive hearing loss DFNA36.
AB  - Despite recent progress in identifying genes underlying deafness, there are still
      relatively few mouse models of specific forms of human deafness. Here we describe
      the phenotype of the Beethoven (Bth) mouse mutant and a missense mutation in Tmc1
      (transmembrane cochlear-expressed gene 1). Progressive hearing loss (DFNA36) and
      profound congenital deafness (DFNB7/B11) are caused by dominant and recessive
      mutations of the human ortholog, TMC1 (ref. 1), for which Bth and deafness (dn)
      are mouse models, respectively.

PMID- 11850624
TI  - Drosophila Crumbs is a positional cue in photoreceptor adherens junctions and
      rhabdomeres.
AB  - Drosophila Crumbs (Crb) is required for apical-basal polarity and is an apical
      determinant in embryonic epithelia. Here, we describe properties of Crb that
      control the position and integrity of the photoreceptor adherens junction and
      photosensitive organ, or rhabdomere. In contrast to normal photoreceptor adherens
      junctions and rhabdomeres, which span the depth of the retina, adherens junctions
      and rhabdomeres of Crb-deficient photoreceptors initially accumulate at the top
      of the retina and fail to maintain their integrity as they stretch to the retinal
      floor. We show that Crb controls localization of the adherens junction through
      its intracellular domain containing a putative binding site for a protein 4.1
      superfamily protein (FERM). Although loss of Crb or overexpression of the FERM
      binding domain causes mislocalization of adherens junctions, they do not result
      in a significant loss of photoreceptor polarity. Mutations in CRB1, a human
      homologue of crb, are associated with photoreceptor degeneration in retinitis
      pigmentosa 12 (RP12) and Leber congenital amaurosis (LCA). The intracellular
      domain of CRB1 behaves similarly to its Drosophila counterpart when overexpressed
      in the fly eye. Our studies may provide clues for mechanisms of photoreceptor
      degeneration in RP12 and LCA.

PMID- 11850625
TI  - Crumbs, the Drosophila homologue of human CRB1/RP12, is essential for
      photoreceptor morphogenesis.
AB  - The apical transmembrane protein Crumbs is a central regulator of epithelial
      apical-basal polarity in Drosophila. Loss-of-function mutations in the human
      homologue of Crumbs, CRB1 (RP12), cause recessive retinal dystrophies, including
      retinitis pigmentosa. Here we show that Crumbs and CRB1 localize to corresponding
      subdomains of the photoreceptor apical plasma membrane: the stalk of the
      Drosophila photoreceptor and the inner segment of mammalian photoreceptors. These
      subdomains support the morphogenesis and orientation of the photosensitive
      membrane organelles: rhabdomeres and outer segments, respectively. Drosophila
      Crumbs is required to maintain zonula adherens integrity during the rapid apical
      membrane expansion that builds the rhabdomere. Crumbs also regulates stalk
      development by stabilizing the membrane-associated spectrin cytoskeleton, a
      function mechanistically distinct from its role in epithelial apical-basal
      polarity. We propose that Crumbs is a central component of a molecular scaffold
      that controls zonula adherens assembly and defines the stalk as an apical
      membrane subdomain. Defects in such scaffolds may contribute to human CRB1
      related retinal dystrophies.

PMID- 11850626
TI  - TOX: an HMG box protein implicated in the regulation of thymocyte selection.
AB  - In the thymus, pre-T cell receptor (pre-TCR)--mediated signaling and then TCR
      mediated signaling initiate changes in gene expression that result in the
      maturation of CD4 and CD8 lineage T cells from common precursors. Using gene chip
      technology, we isolated a murine gene, designated Tox, that encodes a member of
      the HMG (high-mobility group) box family of DNA-binding proteins. TOX expression
      is up-regulated by both pre-TCR and TCR activation of immature thymocytes but not
      by TCR activation of mature naive T cells. Transgenic mice that express TOX show
      expanded CD8+ and reduced CD4+ single positive thymocyte subpopulations. We
      present evidence here that this phenotype results from a perturbation in lineage
      commitment due to reduced sensitivity to TCR-mediated signaling. This molecular
      marker of thymic selection events may therefore play a role in establishing the
      activation threshold of developing T cells and patterning changes in gene
      expression.

PMID- 11850627
TI  - Selective loss of gastrointestinal mast cells and impaired immunity in PI3K
      deficient mice.
AB  - Mice that lack the p85alpha regulatory subunit of phosphatidylinositol-3 kinase
      (PI3K) are deficient in gastrointestinal and peritoneal mast cells but have
      dermal mast cells. Accordingly, these mice show impaired bacterial clearance in
      response to acute septic peritonitis and are highly susceptible to infection by
      the intestinal nematode Strongyloides venezuelensis. Systemic anaphylactic shock
      responses, however, are intact. We found that although reconstitution of
      PI3Kminus sign/minus sign mice with bone marrow--derived mast cells (BMMCs)
      restored anti-bacterial immunity, only T helper type 2 (TH2)-conditioned BMMCs,
      not "standard" BMMCs, were able to restore anti-nematode immunity. This finding
      highlights the importance of the TH2 response in the control of nematode
      infection. Thus, PI3K likely plays an essential role in host immune responses by
      regulating both the development and induction of mast cells.

PMID- 11850628
TI  - Neisserial binding to CEACAM1 arrests the activation and proliferation of CD4+ T
      lymphocytes.
AB  - Infection with Neisseria gonorrhoeae can trigger an intense inflammatory
      response, yet there is little specific immune response or development of immune
      memory. In addition, gonorrhea typically correlates with a transient reduction in
      T lymphocyte counts in blood, and these populations recover when gonococcal
      infection is resolved. Such observations suggest that the gonococci have a
      suppressive effect on the host immune response. We report here that N.
      gonorrhoeae Opa proteins were able to bind CEACAM1 expressed by primary CD4+ T
      lymphocytes and suppress their activation and proliferation. CEACAM1 bound by
      gonococcal Opa52 associated with the tyrosine phosphatases SHP-1 and SHP-2, which
      implicates the receptor's ITIM (immunoreceptor tyrosine-based inhibitory motif)
      in this effect.

PMID- 11850629
TI  - Experience-dependent refinement of inhibitory inputs to auditory coincidence
      detector neurons.
AB  - The spatial arrangement of inputs on to single neurons is assumed to be crucial
      in accurate signal processing. In mammals, the most precise temporal processing
      occurs in the context of sound localization. Medial superior olivary neurons can
      encode microsecond differences in the arrival time of low-frequency sounds at the
      two ears. Here we show that in mammals with well developed low-frequency hearing,
      a spatial refinement of ionotropic inhibitory inputs occurs on medial superior
      olivary neurons during development. This refinement is experience dependent and
      does not develop in mammals that do not use interaural time differences for sound
      localization.

PMID- 11850630
TI  - Rapid turnover of actin in dendritic spines and its regulation by activity.
AB  - Dendritic spines are motile structures that contain high concentrations of
      filamentous actin. Using hippocampal neurons expressing fluorescent actin and the
      method of fluorescence recovery after photobleaching, we found that 85 +/- 2% of
      actin in the spine was dynamic, with a turnover time of 44.2 +/- 4.0 s. The rapid
      turnover is not compatible with current models invoking a large population of
      stable filaments and static coupling of filaments to postsynaptic components. Low
      frequency stimulation known to induce long-term depression in these neurons
      stabilized nearly half the dynamic actin in the spine. This effect depended on
      the activation of N-methyl-D-aspartate (NMDA) receptors and the influx of
      calcium. In neurons from mice lacking gelsolin, a calcium-dependent actin-binding
      protein, activity-dependent stabilization of actin was impaired. Our studies
      provide new information on the kinetics of actin turnover in spines, its
      regulation by neural activity and the mechanisms involved in this regulation.

PMID- 11850631
TI  - Low glucose-sensing cells in the carotid body.
AB  - Decreased plasma glucose concentration elicits a complex neuroendocrine response
      that prevents or rapidly corrects hypoglycemia as required to preserve brain
      function; however, where and how low glucose is sensed is unknown. Here we show
      that low glucose increases secretion from glomus cells in the carotid bodies,
      sensory organs whose stimulation by hypoxia produces sympathetic activation, by a
      process that depends on extracellular Ca2+ influx and is paralleled by inhibition
      of voltage-gated K+ channels. We propose a new glucose-sensing role for the
      carotid body glomus cell that serves to integrate information about blood glucose
      and O2 levels and to activate counterregulatory responses.

PMID- 11850632
TI  - Ventricle-directed migration in the developing cerebral cortex.
AB  - It is believed that postmitotic neurons migrate away from their sites of origin
      in the germinal zones to populate distant targets. Contrary to this notion, we
      found, using time-lapse imaging of brain slices, populations of neurons
      positioned at various levels of the developing neocortex that migrate towards the
      cortical ventricular zone. After a pause in this proliferative zone, they migrate
      radially in the direction of the pial surface to take up positions in the
      cortical plate. Immunohistochemical analysis together with tracer labeling in
      brain slices showed that cells showing ventricle-directed migration in the
      developing cortex are GABAergic interneurons originating in the ganglionic
      eminence in the ventral telencephalon. We speculate that combinations of
      chemoattractant and chemorepellent molecules are involved in this ventricle
      directed migration and that interneurons may seek the cortical ventricular zone
      to receive layer information.

PMID- 11850633
TI  - Humans and great apes share a large frontal cortex.
AB  - Some of the outstanding cognitive capabilities of humans are commonly attributed
      to a disproportionate enlargement of the human frontal lobe during evolution.
      This claim is based primarily on comparisons between the brains of humans and of
      other primates, to the exclusion of most great apes. We compared the relative
      size of the frontal cortices in living specimens of several primate species,
      including all extant hominoids, using magnetic resonance imaging. Human frontal
      cortices were not disproportionately large in comparison to those of the great
      apes. We suggest that the special cognitive abilities attributed to a frontal
      advantage may be due to differences in individual cortical areas and to a richer
      interconnectivity, none of which required an increase in the overall relative
      size of the frontal lobe during hominid evolution.

PMID- 11850634
TI  - Proenkephalin A gene products activate a new family of sensory neuron--specific
      GPCRs.
AB  - Several peptide fragments are produced by proteolytic cleavage of the opioid
      peptide precursor proenkephalin A, and among these are a number of enkephalin
      fragments, in particular bovine adrenal medulla peptide 22 (BAM22). These peptide
      products have been implicated in diverse biological functions, including
      analgesia. We have cloned a newly identified family of 'orphan' G protein-
      coupled receptors (GPCRs) and demonstrate that BAM22 and a number of its
      fragments bind to and activate these receptors with nanomolar affinities. This
      family of GPCRs is uniquely localized in the human and rat small sensory neuron,
      and we called this family the sensory neuron--specific G protein--coupled
      receptors (SNSRs). Receptors of the SNSR family are distinct from the traditional
      opioid receptors in their insensitivity to the classical opioid antagonist
      naloxone and poor activation by opioid ligands. The unique localization of SNSRs
      and their activation by proenkephalin A peptide fragments indicate a possible
      function for SNSRs in sensory neuron regulation and in the modulation of
      nociception.

PMID- 11850635
TI  - Automatic and intentional brain responses during evaluation of trustworthiness of
      faces.
AB  - Successful social interaction partly depends on appraisal of others from their
      facial appearance. A critical aspect of this appraisal relates to whether we
      consider others to be trustworthy. We determined the neural basis for such
      trustworthiness judgments using event-related functional magnetic resonance
      imaging. Subjects viewed faces and assessed either trustworthiness or age. In a
      parametric factorial design, trustworthiness ratings were correlated with BOLD
      signal change to reveal task-independent increased activity in bilateral amygdala
      and right insula in response to faces judged untrustworthy. Right superior
      temporal sulcus (STS) showed enhanced signal change during explicit
      trustworthiness judgments alone. The findings extend a proposed model of social
      cognition by highlighting a functional dissociation between automatic engagement
      of amygdala versus intentional engagement of STS in social judgment.

PMID- 11850636
TI  - A residue-specific view of the association and dissociation pathway in protein-
      DNA recognition.
AB  - Signal propagation in biological systems occurs through a series of inter- and
      intramolecular events, the precise pathways of which remain elusive in most
      cases. With respect to protein--DNA interactions in particular, little is known
      about the association and dissociation reaction pathways. Here we show that the
      exchange of amide protons detected by NMR can be used to characterize, at residue
      level, the mechanism, kinetics and thermodynamics of Lac headpiece (HP)
      interaction with DNA operators. Specific protein--DNA contacts responsible for
      the direct readout of the sequence are formed and broken at distinct time scales.
      Unfolding of the hinge helices triggers protein--DNA dissociation by progressive
      destabilization of distinct structural units, which is facilitated by the low
      stability of the protein in the uncomplexed state. Upon DNA binding, a dramatic
      alteration in the dynamics of the protein is observed, which may be used
      advantageously by the biological system to switch between functional states.
      Hydrogen-deuterium exchange can provide an unusually detailed view of the
      interaction mechanism of a protein--DNA complex and the associated energetics of
      DNA recognition with residue-level specificity.

PMID- 11850639
TI  - Editorial: Deferred Consent: Issues In Clinical Research.

PMID- 11850637
TI  - Crystal structure of the human TbetaR2 ectodomain--TGF-beta3 complex.
AB  - Transforming growth factor-beta (TGF-beta) is the prototype of a large family of
      structurally related cytokines that play key roles in maintaining cellular
      homeostasis by signaling through two classes of functionally distinct Ser/Thr
      kinase receptors, designated as type I and type II. TGF-beta initiates receptor
      assembly by binding with high affinity to the type II receptor. Here, we present
      the 2.15 A crystal structure of the extracellular ligand-binding domain of the
      human TGF-beta type II receptor (ecTbetaR2) in complex with human TGF-beta3.
      ecTbetaR2 interacts with homodimeric TGF-beta3 by binding identical finger
      segments at opposite ends of the growth factor. Relative to the canonical
      'closed' conformation previously observed in ligand structures across the
      superfamily, ecTbetaR2-bound TGF-beta3 shows an altered arrangement of its
      monomeric subunits, designated the 'open' conformation. The mode of TGF-beta3
      binding shown by ecTbetaR2 is compatible with both ligand conformations. This, in
      addition to the predicted mode for TGF-beta binding to the type I receptor
      ectodomain (ecTbetaR1), suggests an assembly mechanism in which ecTbetaR1 and
      ecTbetaR2 bind at adjacent positions on the ligand surface and directly contact
      each other via protein--protein interactions.

PMID- 11850638
TI  - The essential histone variant H2A.Z regulates the equilibrium between different
      chromatin conformational states.
AB  - Explaining the determinants involved in regulating the equilibrium between
      different chromatin structural states is fundamental to understanding
      differential gene expression. Histone variant H2A.Z is essential to chromatin
      architecture in higher eukaryotes but its role has not yet been explained. We
      show here that H2A.Z facilitates the intramolecular folding of nucleosomal arrays
      while simultaneously inhibiting the formation of highly condensed structures that
      result from intermolecular association. This makes a case for H2A.Z playing a
      fundamental role in creating unique chromatin domains poised for transcriptional
      activation. These results provide new insights into understanding how chromatin
      fiber dynamics can be altered by core histone variants to potentially regulate
      genomic function.

PMID- 11850640
TI  - Discrepancy between Bioavailability and Hypotensive Effect of Oral and Sublingual
      Nifedipine.
AB  - Nifedipine, 10-mg capsules, were given orally and sublingually to six healthy
      volunteers according to a randomized crossover design. Nifedipine plasma levels,
      blood pressure, and heart rate were determined at several times after medication.
      C(max) was higher (134 plus minus 17 vs. 93 plus minus 2 ng ml(minus sign1), mean
      plus minus SD, P < 0.01) and occurred earlier (0.5 vs. 1 h) with oral than with
      sublingual nifedipine. However, there was no significant difference in AUC (268
      plus minus 56 vs. 288 plus minus 35 ng h ml(minus sign1)) nor in t(1/2) (1.8 plus
      minus 0.2 vs. 1.9 plus minus 0.3 h), indicating that sublingual administration
      decreased the rate but not the extent of nifedipine absorption. Notwithstanding
      the difference in C(max), both routes yielded a similar reduction in diastolic
      blood pressure of 13 plus minus 1 mm Hg. Heart rate increase, which reflects the
      activation of homeostatic mechanisms, was greater with oral than with sublingual
      nifedipine, that is, 18 plus minus 1 vs. 13 plus minus 1 beats min(minus sign1),
      P < 0.01. It is concluded that slower absorption after sublingual administration
      increases nifedipine hypotensive efficiency by producing less counteracting
      homeostatic responses than the more rapidly absorbed oral nifedipine.

PMID- 11850641
TI  - Antiplatelet Effect of Nifedipine depending on its Action on Red Cell
      Deformability in Essential Hypertension.
AB  - In patients with essential hypertension, increased level of platelet activity
      expressed as the concentrations of beta-thromboglobulin (beta-TG) and platelet
      factor 4 (PF4) were observed. Elevation of the levels of both beta-TG and PF4
      correlated with the increase in platelet aggregability in platelet-rich plasma
      (PRP) and the decrease in red blood cell deformability, which were considered as
      being the possible factors for the platelet intravascular activation. After 2
      weeks of monotherapy with nifedipine (40 mg daily), a decrease in platelet
      aggregability in PRP was observed in 35 of the 75 patients and an increase in red
      cell deformability in 37 of the 75 patients. Using cluster analysis, all cases
      were divided into several groups based on nifedipine effects on red cell
      deformability and platelet aggregability in PRP. It was revealed that the
      statistically significant decrease in the levels of platelet markers took place
      only in patients in whom nifedipine simultaneously decreased platelet
      aggregability and increased red cell deformability. Analysis of variance showed a
      high power of influence for combined changes in these parameters for reducing
      intravascular platelet activation by nifedipine. It is suggested that nifedipine
      reduces platelet activity by direct action on platelets and indirectly due to its
      capacity to increase red cell deformability, resulting in elimination of platelet
      stimulation by red blood cells.

PMID- 11850643
TI  - Comparative Pharmacokinetics and Bioavailability of Dilacor XR and Cardizem CD in
      Healthy Volunteers.
AB  - The objective of this investigation was to compare the single-dose and steady
      state pharmacokinetic profiles of Dilacor XR to Cardizem CD. The study enrolled
      24 healthy males and was divided into three parts: a single intravenous 25-mg
      bolus dose of diltiazem HCl (Cardizem Injectable) followed by a two-way crossover
      comparison of single and multiple once-daily 240-mg oral doses of Dilacor XR and
      Cardizem CD. Plasma samples were analyzed for diltiazem using a specific and
      sensitive HPLC assay. Statistical analysis and deconvolution were performed on
      the data. A 1- and 3-hour lag time in diltiazem absorption was noted following
      the administration of Dilacor XR and Cardizem CD, respectively. Statistically
      significant differences were noted in mean single- and multiple-dose t(max)
      values with Cardizem CD taking approximately twice as long as Dilacor XR to reach
      C(max). Dilacor XR was equivalent to Cardizem CD with respect to AUC((0--infty
      infinity)) and C(max). Equivalent minimum and average steady-state plasma
      diltiazem concentrations were noted after multiple-dose administration.
      Deconvolution of the single-dose data also showed similar mean bioavailabilities
      for the respective formulations but revealed dissimilarities in each product's
      absorption profile that may reflect observed differences in absorption lag time
      and t(max).

PMID- 11850642
TI  - Pharmacokinetics of Nisoldipine Coat--Core Formulation in Subjects with Liver
      Cirrhosis.
AB  - The pharmacokinetics of a controlled-release formulation (coat--core) of the
      calcium channel blocker nisoldipine was investigated in eight subjects with
      biopsy-proved liver cirrhosis and eight healthy subjects. In Stage I, subjects
      received a single 10-mg dose to determine if this dose would be safely tolerated
      in the subjects with cirrhosis. Because all subjects in both groups tolerated the
      dose without difficulty, all were continued to Stage II. In Stage II, subjects
      received a once-daily dose of 10-mg coat-core tablets for 7 days. Serial plasma
      samples were assayed for nisoldipine in both stages. The C(max) and AUC of
      nisoldipine were approximately fourfold to fivefold higher (p < 0.01) in subjects
      with cirrhosis as compared to healthy subjects; however, there was overlap in the
      range of pharmacokinetic parameters between the two groups. The accumulation
      factor following multiple dosing was similar in both groups. Results suggest that
      nisoldipine dose should be optimized by monitoring of a pharmacodynamic end
      point, such as effect on blood pressure. It is likely that dose requirements for
      patients with liver disease will be lower.

PMID- 11850644
TI  - Recurrent Induction of the Syndrome of Inappropriate Antidiuretic Hormone
      Secretion Following Carotid Endarterectomy.

PMID- 11850645
TI  - Randomized Placebo-Controlled Withdrawal Study of Amlodipine in Agina Pectoris.
AB  - OBJECTIVES: To assess the antianginal and antiischemic efficacy, safety, and the
      potential for tolerance or withdrawal effects of amlodipine. BACKGROUND: The slow
      onset of action and long half-life of amlodipine may help avoid withdrawal
      effects such as the exacerbation of angina and precipitation of myocardial seen
      with beta-blockers. METHODS: After a 2-week single-blind placebo run-in period,
      226 patients with stable exertional angina pectoris were given amlodipine
      (starting at 5 mg day(minus sign1) and titrated to 10 mg day(minus sign1)) in a
      single-blind fashion for 8 weeks. One hundred seventy-two responders (greater
      than-or-equal7% improvement in symptom-limited exercise time) entered a 4-week
      double-blind withdrawal phase and randomly received continued treatment with
      amlodipine (n = 91) or placebo (n = 81). RESULTS: Treatment with amlodipine
      increased the exercise capacity by 14% and improved time to angina onset by 25%
      and time to 1-mm ST segment deviation by 18%. These variables remained
      essentially unchanged at the end of the 4-week withdrawal phase for the group
      continued on amlodipine (+0.8%, +3.2%, and +2.0%, respectively) but decreased for
      the group on placebo (minus sign5.8%, minus sign9.8%, and minus sign11.0%,
      respectively) (p < 0.001 between groups, all assessments) to values similar to
      those obtained during the initial placebo run-in period. Approximately one-third
      of the patients responded to 5 mg amlodipine during single-blind therapy and
      according to "usual clinical practice" remained on this dose. The results of
      randomized withdrawal in the subgroup receiving 5 mg also favored amlodipine over
      placebo. Side effects were reported by 47% of patients on amlodipine and by 22%
      of patients receiving placebo. The most frequently reported side effects for

PMID- 11850646
TI  - The Effect of Omeprazole on Serum Concentrations of Theophylline, Pepsinogens A
      and C, and Gastrin in Elderly Duodenal Ulcer Patients.
AB  - With the aim of verifying the effect of omeprazole treatment on theophyline serum
      concentration in elderly peptic ulcer patients, we studied 10 male subjects aged
      >65 years (mean age = 75.2, range = 67--86) with chronic obstructive
      bronchopneumonia and endoscopically diagnosed duodenal ulcer in acute phase. All
      subjects were treated with a slow-release formulation of theophylline 200 mg
      b.i.d. plus omeprazole 20 mg daily for 4 weeks. In all subjects serum
      concentrations of azote, creatinine, theophylline were determined at the
      beginning and after 1 and 4 weeks; at the beginning and end of the study,
      pepsinogen group A (PGA), pepsinogen group C(PGC) and gastrin were measured.
      Statistical analysis was performed with the Student's t-test for paired data. The
      results showed no statistically significant differences after 1 and 4 weeks of
      omeprazole treatment in serum concentrations of theophylline (T(0) = 7.4, T(1
      week) = 7.5, T(4 weeks) = 6.0, p = ns), azote (T(0) = 45.2, T(1 week) = 30.5, T(4
      weeks) = 36.1, p = ns), creatinine (T(0) = 1.27, T(1 week) = 1.02, T(4 weeks) =
      1.16, p = ns), PGA (T(0) = 99.5, T(4 weeks) = 126.2, p = ns), and PGC (T(0) =
      10.6, T(4 weeks) = 12.1, p = ns); however serum gastrin increased from T(0) =
      70.2 plus minus 13.2 to T(4 weeks) = 130.3 plus minus 18.3 (p < 0.0001). It was
      concluded that (1) serum concentration of theophylline is not affected by the
      concomitant omeprazole treatment lasting 1 month in elderly patients suffering
      from chronic obstructive bronchopneumonia and peptic ulcer, (2) modifications of
      dosages of theophylline and/or omeprazole are not necessary in the elderly with
      normal renal function, (3) the increase in fasting serum gastrin after 4 weeks of
      treatment may indicate that omeprazole 20 mg daily is efficacious in inhibiting
      gastric acid secretion in the elderly people.

PMID- 11850647
TI  - Individual Variability of Carbonyl Reductase Activity for Acetohexaminde in Human
      Erythorcytes.
AB  - Acetohexamide, an oral antidiabetic agent, is metabolized by carbonyl reductase
      to hydroxyhexamide, which has a higher hypoglycemic potency than the parent
      compound. In the present study, interindividual variability of carbonyl reductase
      activity in erythrocyte was examined. Enzyme activity in 31 healthy subjects
      (23.9 plus minus 3.4 years, mean plus minus SD) was monitored by measuring
      formation of hydroxyhexamide using HPLC methods. Using 0.5 mM acetohexamide as
      substrate, reductase activity of 6.06 plus minus 0.06 nmol min(minus sign1)
      gHb(minus sign1) (range: 5.9--6.2) with a coefficient of variation of 15% was
      observed in erythrocytes. Acetohexamide-reducing activity in erythrocytes showed
      a normal distribution and the interindividual variability of the reductase
      activity was found to be small, implying that the large variability reported for
      the acetohexamide plasma half-life is not caused by the amount of reductase
      enzyme in erythrocytes.

PMID- 11850648
TI  - Rate of Distribution of Eethanol into the Total Body Water.
AB  - Nonequilibrium distribution of ethanol in the total body water (TBW) has
      implications for understanding gross intoxication seen after rapid consumption of
      alcohol and for certain new clinical monitoring methods where ethanol is used as
      a tracer. We studied the rate of distribution of ethanol into the TBW from the
      concentration--time profiles in whole blood after 0.4 g kg(minus sign1) of
      ethanol was given by intravenous over 15, 30, 45, and 60 min to six female
      volunteers. We also gave these females 0.6 g kg(minus sign1) over 30 min, and
      five young males 0.4 g kg(minus sign1) over 30 min. The results suggest that the
      blood ethanol concentration after rapid infusion can be described by a two
      compartment model with first-order distribution kinetics and zero-order
      (saturated Michaelis--Menten) elimination. Distribution of ethanol occurred with
      a half-time of 6.6 plus minus 2.6 min (mean plus minus SD). Alcohol intoxication
      was more pronounced when ethanol was given rapidly. We conclude that predictable
      differences in the concentration of ethanol between the blood and the peripheral
      tissues during rapid supplementation of ethanol causes higher concentrations in
      blood and a more pronounced intoxication.

PMID- 11850649
TI  - Determination of Three Acetylator Phenotypes in a Mexican Population Using
      Sulfamethazine Metabolic Ratio.
AB  - Eighty-six Mexican young healthy volunteers received a 500-mg oral sulfamethazine
      dose. Urine was collected 0--6 h after medication and acetylated, and unchanged
      sulfamethazine were determined by the Bratton--Marshall method. The frequency
      distribution of acetylated/unchanged sulfamethazine, determined by probit
      analysis, appeared to be trimodal, allowing the discrimination of three
      acetylator phenotypes. The frequencies of rapid, intermediate, and slow
      acetylators were 28%, 42%, and 30% respectively, being consistent with the Hardy
      Weinberg law.

PMID- 11850651
TI  - Charcoal and Rifampicin Pharmacokinetics.
AB  - We investigated the effect of activated charcoal on rifampicin disposition in six
      healthy subjects. On three occasions (control, phases II and III, separated by 1
      week), each subject received 600 mg of rifampicin with 350 ml of water. On the
      second and third occasions (phases II and III), each subject received in addition
      to 600 mg of rifampicin and 7.5 and 15 g of activated charcoal, respectively, in
      350 ml of water as charcoal slurry. Plasma rifampicin levels were measured from 1
      to 24 h postrifampicin ingestion. Treatment with activated charcoal significantly
      increased the clearance and decreased the maximum peak concentration, half-lives
      and area under the curves as compared with control treatment without activated
      charcoal.

PMID- 11850650
TI  - Pharmacokinetics and Safety of a Potential Antidementia Compound, CL 275,838,
      after Multiple Oral Doses in Patients with Dementia of Alzheimer Type or Vascular
      Dementia.
AB  - The multiple-dose pharmacokinetics and safety of a new potential antidementia
      compound, CL 275,838, were examined in two randomized, double-blind, parallel
      group, placebo-controlled studies. The Alzheimer Disease Assessment Scale (ADAS)
      was employed to preliminarily assess the patients' cognitive and the behavioral
      profiles. In the first study, nine patients with Alzheimer type or vascular
      dementia were treated for 2 weeks with daily doses of 50 mg. In the second study,
      nine other patients, selected with the same inclusion/exclusion criteria and
      treated following the same experimental design, were given 100 mg day(minus
      sign1) CL 275,838. At the lower dose, no side effects were detected; in the 100
      mg day(minus sign1) study, mild drowsiness (one patient) and moderate agitation
      (two patients) were observed. Laboratory tests showed no changes in either study,
      apart from a slight, transient increase in serum bilirubin in one patient given
      100 mg. At the dose of 50 mg, no patients showed any modification on the ADAS,
      whereas three patients given 100 mg showed some improvement. During the 2 weeks
      of oral dosing, predose plasma concentrations of the parent compounds and its
      metabolites II and IV increased but not in proportion to the dose, although at
      both doses, accumulation was essentially complete within 10 days. At 50 mg, the
      mean steady-state C(max) and C(ss) of the parent compound were similar to those
      reached in young males after a comparable regimen. Mean steady-state metabolite
      to-parent drug ratios were higher in patients than in healthy individuals,
      although there was wide variation in our patient group. Mean washout t(1/2) of
      the parent compound (34 h) and its metabolites II (37 h) and IV (41 h) were
      longer than in young men and were similar in all cases to those observed after
      single doses in healthy elderly subjects. After 100 mg, mean C(max) and C(ss) of
      the unchanged compound rose more than proportionally and the apparent t(1/2)
      tended to rise, compared with the lower dose. Mean steady-state oral clearance
      decreased, changing the metabolite-to-parent drug ratios, suggesting nonlinear
      kinetics after several relatively high oral doses. This might explain why the
      higher dose was less well tolerated.

PMID- 11850653
TI  - The Calcium Channel Blockers.

PMID- 11850652
TI  - Lack of Clinically Relevant Interaction of Cetirizine on Theophylline Disposition
      in Healthy Subjects: A Placebo-Controlled Study.
AB  - The possible interaction of a steady-state cetirizine treatment, a nonsedating
      H(1) antihistamine, on the disposition of a single I.V. infusion of theophylline
      was studied in six healthy male volunteers. As a corollary, it was checked
      whether this single theophylline administration modified the steady-state
      condition of cetirizine. A three-period, two-treatment, crossover design was
      used, each period being separated by a washout of 1 week. Each period consisted
      of the oral administration of 10 mg cetirizine or of a matching placebo every 12
      h for 31/2 days, the last intake being followed, 1 hour later, by a single 1-h
      I.V. infusion of 240 mg theophylline or of placebo. The sequence of treatments (A
      = cetirizine + theophylline placebo, B = cetirizine placebo + theophylline, C =
      cetirizine + theophylline) was alloted by a double Latin-square randomization.
      The repeated administration of cetirizine induced a 3% decrease of the urinary
      elimination of unchanged theophylline; the total body clearance of theophylline
      was marginally (+5%) and not significantly modified. Theophylline slightly
      lengthened the elimination half-life of cetirizine (from 8.3 to 9.9 h), without
      modification of its apparent total body clearance; the half-life of cetirizine
      remaining in the normal range. These subtle modifications are not clinically
      relevant and it may, thus, be considered that cetirizine exerts no pertinent
      interaction on theophylline disposition.

PMID- 11850654
TI  - Antiarrhythmic Drug Development: Classification and its Impact on Development.
AB  - Antiarrhythmic therapy would be greatly facilitated if the patients most at risk
      of sudden death could be identified. The Lown classification of the "severity" of
      arrhythmias is unsatisfactory. Recent attention has been directed to dispersion
      of depolarization, measured by signal averaging of the terminal QRS complex, and
      to dispersion of repolarization, measured by comparing QT intervals in different
      leads of the ECG. Since the Cardiac Arrhythmia Suppression Trial (CAST) therapy
      with Class 1 agents, especially Class 1c, if used at all, has been diverted from
      attempts to suppress arrhythmias and limited to control of symptoms. Interest in
      new Class 3 agents has grown and several new compounds are under trial. Low-dose
      treatment with the original Class 3 drug, amiodarone, has yielded promising
      results, in that mortality and serious arrhythmias have been reduced by regimes
      which do not fully abolish the arrhythmia.

PMID- 11850655
TI  - Effect of Food on the Multiple-Peak Behavior After a Single Oral Dose of
      Diclofenac Sodium Slow-Release Tablet in Humans.
AB  - This study evaluated the effect of a standard meal on the multiple-peak behavior
      of diclofenac sodium following oral administration of a 100-mg slow-release (SR)
      wax-matrix tablet. The study was a randomized, 3 * 3 Latin-square trial balanced
      for residual effects, in which 18 subjects were randomly assigned to treatment
      sequences consisting of three treatments: (A) one 100-mg SR tablet, fasted; (B)
      one 100-mg SR tablet, fed; and (C) 100-mg diclofenac sodium buffered aqueous
      solution, fasted. Blood samples were obtained over a 24-h period for Treatments A
      and B, and over an 8-h period for Treatment C. Food did not significantly affect
      the extent of absorption but generally delayed the onset of absorption from the
      SR tablet. The plasma concentration-time profile for the SR tablet under fasted
      conditions was characterized by multiple-peak behavior. Under fed conditions, the
      SR tablet showed a more consistent absorption pattern, with a single peak
      occurring usually between 5 and 6 h. The concentration-time profile of the
      buffered aqueous solution showed a very rapid absorption phase followed by a
      rapid decline and a terminal elimination half-life of approximately 1.8 h. A
      single peak was observed following the buffered aqueous solution. This
      observation, in conjunction with evidence from other studies, leads to the
      conclusion that gastrointestinal pH may be responsible for the multiple-peak
      behavior observed following diclofenac sodium dosing. As compared to the
      solution, the was-matrix tablet under both fasted and fed conditions showed slow
      release, characteristics.

PMID- 11850656
TI  - Effect of Quinapril on the Circadian Blood Pressure Pattern Evaluated by Periodic
      Analysis of Covariance.
AB  - The effects of quinapril on casual blood pressure (BP) and circadian variations
      in 24-h blood pressure (24ABPM) were studied in patients with essential
      hypertension. Twenty-six patients were enrolled in the study (mean age 59 plus
      minus 11 years). After a 4-week washout period, patients, were treated with
      quinapril 5 mg, 10 mg, or 20 mg once a day until casual blood pressures become
      optimal within 8--10 weeks. The 24ABPM was performed before and after treatment
      at 30-min intervals using an ABPM-630 in patients during usual daily activities
      on the work days. Measured BP was fitted to a periodic regression curve with 24-h
      and 12-h harmonics. Quinapril significantly decreased casual blood pressure but
      had no effect on pulse rate. It exhibited an excellent antihypertensive effect
      throughout 24 h; this effect, however, was stronger during the day than at night,
      resulting in no excessive nocturnal hypotension. The level of the periodic
      regression curves for systolic and diastolic blood pressures was significantly
      decreased following treatment but that of the pulse rate was not affected by this
      drug. The drug caused changes in the pattern of the periodic regression curve for
      blood pressure and pulse rate. This was attributed to the more prominent
      antihypertensive effect of quinapril in the afternoon and evening. To evaluate
      the efficacy of this drug semiquantitatively, the hyperbaric indices were
      compared before and after the treatment, and those indices for both systolic and
      diastolic blood pressures were significantly decreased. Adverse effects occurred
      in four patients (15.4%), all of which were mild and thought to be clinically
      insignificant. It was concluded that quinapril, 5--20 mg day(minus sign1), was
      considered to be useful for patients with mild to moderate essential
      hypertension.

PMID- 11850657
TI  - Hemodynamic Effects of Dilevalol Following Acute and Long-Term Administration in
      Normal and Hypertensive Subjects.
AB  - Forearm hemodynamics using pulsed Doppler flowmetry were studied in 12 healthy
      volunteers and 20 patients with mild to moderate hypertension before and after
      acute and long-term oral administration of the beta-blocking agent dilevalol. The
      study was performed using a double-blind design versus placebo. Both 200-mg and
      400-mg dosages produced a significant acute blood pressure reduction in
      normotensive and hypertensive subjects. In hypertensive subjects, forearm
      vascular resistance was poorly modified, brachial artery diameter decreased
      significantly but only with long-term administration of the 400-mg dosage. A
      significant reduction in brachial artery tangential tension was consequently
      observed. The study provides evidence that Dilevalol produced a significant
      decrease in blood pressure in normotensive and hypertensive subjects in
      association with a decrease in brachial artery tangential tension.

PMID- 11850658
TI  - Central Acting Antihypertensive Drugs: Past, Present, and Future.
AB  - The central antihypertensive drugs such as methyldopa or clonidine have been
      agents of importance in the therapy of hypertension. Due to the side effects and
      the rebound hypertensive phenomenon in the case of clonidine, the use of these
      agents have been clearly diminished. There are several evidences that a new type
      of receptor, imidazoline receptor, is present in the central nervous system and
      in the periphery. A specific agonist for these receptors, rilmenidine, has been
      studied in experimental animals and in hypertensive patients. Clinical studies
      have shown that rilmenidine exhibits similar efficacy but a better tolerability
      compared to clonidine. Rilmenidine may represent a good alternative in the
      therapy of hypertension.

PMID- 11850659
TI  - Hemodynamic Responses to Papaverine: Do Nitric Oxide, Cyclic GMP, or Calcium
      Mediate the Vasodilation?
AB  - Papaverine is a commonly used vasodilator of the internal mammary artery in
      cardiac surgery. The effects of papaverine with and without N(omega)-L-arginine
      methyl ester (L -NAME) (a nitric oxide production inhibitor) and/or zaprinast (a
      cyclic GMP inhibitor) or verapamil (calcium channel antagonist) on systemic
      vascular resistance in vivo have not been well documented. This study examines
      the hemodynamic responses to papaverine and attempts to identify the role of
      nitric oxide, cyclic guanosine monophosphate (GMP), and calcium in the
      vasodilation. The effects of varying doses of papaverine were evaluated with and
      without L-NAME and/or zaprinast or verapamil on the hindlimb vascular resistance
      in the male rat. With institutional approval, 40 male Sprague--Dawley rats (400-
      450 g) were anesthetized with intraperitoneal pentobarbital (50 mg kg(minus
      sign1)). The carotid artery, jugular vein, and abdominal aorta were cannulated by
      cutdown; mean arterial pressure (MAP) and hindlimb perfusion pressure (HPP) were
      recorded. Rats were heparinized (1000 U kg(minus sign1)). Papaverine (1, 3, 10,
      30, and 100 &mgr;g) was injected into the hindlimb, whereas MAP was maintained
      constant, and the HPP was recorded. Both L-NAME (25 mg kg(minus sign1)) and/or
      verapamil and then papaverine (1, 3, and 10 &mgr;g) were injected into the
      hindlimb, and changes in HPP were recorded. A Student's t-test was used for
      statistical analysis, with a p < 0.05 considered significant. Papaverine, in
      increasing doses, decreased HPP incrementally. L-NAME partially blocked the
      effects of papaverine (p < 0.05), as did verapamil (p < 0.05). The combination of
      L-NAME and verapamil further decreased papaverine's vasodilation to almost
      eliminate it (p < 0.05). We demonstrated the effect of papaverine on the hindlimb
      vasculature is similar to its effects noted in the internal mammary artery.
      Nitric oxide is known to be an agent causing vasodilation. It was demonstrated
      that papaverine vasodilation in the hindlimb vascular bed is modified by L-NAME,
      which suggests that nitric oxide production inhibition is partially responsible
      for this effect. It was demonstrated that there is an effect of calcium channel
      blockade on the vasodilation caused by papaverine. Both L-NAME and verapamil
      together appear to modify further the vasodilation caused by papaverine,
      suggesting both calcium channel and nitric oxide mechanisms for vasodilation.
      Zaprinast, a specific cyclic GMP phosphodiesterase inhibitor, did not effect the
      vasodilation caused by papaverine, acetylcholine, nitroglycerin, or verapamil.

PMID- 11850660
TI  - Chronokinetics of Pravastatin Administered in the PM Compared with AM Dosing.
AB  - Pravastatin, an HMG CoA reductase inhibitor used in the treatment of
      hypercholesterolemia, is recommended for bedtime (PM) dosing. Bedtime dosing with
      pravastatin is slightly more efficacious but not significantly different than
      morning (AM) dosing in lowering LDL-C and total cholesterol. The pharmacokinetics
      of pravastatin and its major metabolite SQ 31,906 were determined in 20 healthy
      men administered a single 20-mg dose either in the morning or at bedtime in an
      open, randomized, crossover study. Concentrations of pravastatin and SQ 31,906
      were measured in serum and urine by gas chromatograph/mass spectrometry
      methodology. The area under the serum concentration time curve (AUC) of
      pravastatin was significantly less (40%) following PM dosing compared with AM
      dosing. Urinary excretion of pravastatin following PM dosing was also
      significantly decreased. Bioavailability of SQ 31,906 was somewhat higher in the
      PM group (20% greater following PM administration), and urinary excretion of SQ
      31,906 was significantly increased by 60% following PM dosing. The lower AUC of
      pravastatin following PM dosing does not diminish its efficacy, possibly because
      PM dosing immediately precedes the diurnal peak period of hepatic cholesterol
      synthesis. Lower blood levels of pravastatin following PM dosing may contribute
      to its favorable safety profile.

PMID- 11850661
TI  - Ranolazine: A New Anti-Ischemic Drug Which Affects Myocardial Energetics.
AB  - Ranolazine is a new, orally active pharmacologic agent that experimentally has
      been shown to favorably affect myocardial metabolism during myocardial ischemia.
      It has no direct action on myocardial hemodynamics but appers to improve
      ventricular functioning by blocking uptake of free fatty acids by the heart while
      shifting metabolism to anaerobic glycolysis during myocardial ischemia.
      Preliminary clinical studies suggest a dose-dependent antianginal, and anti
      ischemic effect and an excellent safety profile for this unique drug. However,
      the results of a recent double-blind efficacy and safety study showed no
      antianginal effect of ranolazine (30--120 mg thrice daily) when compared to
      placebo.

PMID- 11850662
TI  - Bioavailability Study of Nizatidine When Administered in Food.
AB  - A single-center, open-label, four-way crossover study was performed in 22 healthy
      adult subjects to determine the relative effect and significance of certain foods
      on the bioavailability of nizatidine. Results indicate that administration of
      nizatidine mixed with apple sauce, cranberry juice, or vegetable juice reduces
      the bioavailability approximately 30--40% relative to administration of a
      nizatidine capsule with water. The reduction of bioavailability appears to be
      primarily due to reduced extent of absorption. The mechanism of this effect was
      not investigated.

PMID- 11850663
TI  - Computerized ICU Orders Versus Handwritten ICU Orders: A Prospective, Pharmacy
      Based Analysis.
AB  - OBJECTIVE: To compare computerized ICU order writing with handwritten ICU
      physician orders. DESIGN: Prospective study. SETTING: Medical and surgical
      Intensive Care Units and pharmacy of a Department of Veterans Affairs Medical
      Center. PATIENTS: Two hundred sixty-four individual sets of orders.
      INTERVENTIONS: A time study and problem analysis were performed in the pharmacy
      as orders were received and processed. MEASUREMENTS AND MAIN RESULTS: Two hundred
      sixty-four sets of orders were evaluated; MICU (handwritten; n = 133) and SICU
      (computerized; n = 131). Physician length of training are similar in both units.
      The patient age and number of major diagnoses per patient in the two ICU groups
      were similar. Significantly less time (min) (MICU 2.5 +/- 0.3 versus SICU 1.84 +/
      0.1, p < 0.05) is required to review SICU orders. The SICU had significantly
      fewer order problems (MICU 45 versus SICU 12, p < 0.05). Computerized SICU orders
      were corrected more rapidly. The majority of order problems in both groups were
      resolved by telephone. CONCLUSIONS: ICU orders by computer program are processed
      more rapidly, have fewer errors, and are corrected more rapidly than standard
      handwritten orders. We conclude that a dedicated ICU computerized order-writing
      system permits orders to be written with fewer errors and the pharmacy to process
      them more efficiently than handwritten orders.

PMID- 11850664
TI  - Involvement of Elevated Intracellular and Extracellular ATP in the Regulation of
      Insulin Secretion: Therapeutic Targets in Non-Insulin-Dependent Diabetes
      Mellitus.
AB  - Non-insulin-dependent diabetes mellitus (NIDDM) is a heterogeneous disease
      resulting primarily from a variety of pancreatic beta-cell disorders and insulin
      resistance. Whereas insulin resistance, which constitutes a defect in insulin
      action, increases the risk of developing NIDDM and, as such, is a predictor of
      the onset of this disease, it is mostly the beta-cell dysfunction in regulating
      insulin secretion which yields the chronic hyperglycemia with all its associated
      clinical complications. The individual steps in the secretory pathway of insulin
      which is induced primarily by blood plasma glucose have now been identified. The
      transport of the sugar into the beta-cell is followed by its phosphorylation as
      the rate-determining step. The glycolytic metabolism of glucose-6-phosphate leads
      to the generation of ATP resulting in increases in beta-cell ATP pools (steady
      state-levels) as well as ATP/ADP ratios, which, in turn, produce the closure of
      ATP-sensitive K(+) channels, thus depolarizing the beta-cell membrane and opening
      of Ca(2+) channels. The resulting influx of extracellular Ca(2+) and the increase
      in recruitment of Ca(2+) from intracellular stores in response to extracellular
      signals yield an increase in total [Ca(2+)](i) which activates the granular
      insulin secretory machinery. The intracellular beta-cell ATP pools have a key
      role in transducing the signals of the stimulus-secretion coupling pathway and
      toxins such as alloxan and streptozotocin which produce experimental diabetes in
      animals act by damaging mitochondrial oxidative phosphorylation, leading to
      permanent decreases in cellular ATP pools which, due to the sensitivity of beta
      cell function to these pools, manifest itself as a form of diabetes. In addition
      to the major effects of blood plasma glucose in the regulation of insulin
      secretion, a variety of hormonal and neural factors producing endocrine and
      paracrine effects modulate and fine-tune beta-cell insulin secretion. The
      enteroinsular axis provides a linkage between the gastrointestinal tract and
      pancreatic beta-cells stimulus-secretion pathway. Although a powerful effect of
      ATP on insulin secretion was demonstrated more than 30 years ago, only recently
      has it been shown that beta-cells possess P(2)-purinoceptors. Extracellular ATP
      and its synthetic agonists are insulin secretagogues by virtue of their
      activation of membrane purinergic receptors which is coupled to increases in
      extracellular Ca(2+) influx and mobilization of Ca(2+) from internal stores
      resulting in insulin release from beta-cell granules. The physiological
      significance of extracellular ATP regulation of insulin secretion as well as the
      physiological source of these ATP pools have not yet been established. It has
      been recently demonstrated that the administration of adenine nucleotides in vivo
      can yield significant increases in tissue, blood (red blood cell), and blood
      plasma ATP pools. Increasing pancreatic beta-cell intracellular and blood plasma
      (extracellular) pools of ATP is a new therapeutic modality in non-insulin
      dependent diabetes mellitus.

PMID- 11850665
TI  - Allergic and Nonallergic Rhinitis: Update on Pathophysiology and Clinical
      Management.
AB  - An understanding of the pathophysiology will dictate appropriate therapy for
      allergic and nonallergic rhinitis. Cholinergic pathways when stimulated produce
      typical secretions that can be identified by their grandular constituents so as
      to implicate neurologic stimulation. By contrast secretions typical of increased
      vascular permeability are found in allergic reactions and upper respiratory
      infections. In general it is worthwhile to treat early since the nose can be
      primed so as to produce symptoms at lower doses as the season continues. The
      mainstay of therapy continues to be antihistamines, which typically treat the
      sneezing, runny nose, and itchy eyes, nose and throat. The decongestants can
      ameliorate stuffy nose and systemic agents, such as phenylpropanolamine or
      pseudoephedrine, are preferred over the topical agents. Anti-inflammatory
      preparations such as Nasalcrom or steroid aerosols such as those containing
      belcomethasone, funisolide, budesonide, or Triamcinolone can prove very useful.
      If a neurologic mechanism or predominantly rhinorrhea symptoms are present, an
      anticholinergic such as a ipratropium might be the treatment of choice.
      Immunotherapy also is anti-inflammatory and blocks late phase allergic reactions,
      so the choices of medication based on pathogenic mechanisms represents sensible
      treatment options for rhinitis.

PMID- 11850666
TI  - Practice Guidelines, Consensus Conferences: The Pros and Cons.

PMID- 11850667
TI  - Commentary: Over-the-Counter H(2)-Receptor Antagonists: Perhaps the Time Has
      Come!

PMID- 11850668
TI  - Self-Directed Treatment of Intermittent Heartburn: A Randomized, Multicenter,
      Double-Blind, Placebo-Controlled Evaluation of Antacid and Low Doses of an H(2)
      Receptor Antagonist (Famotidine).
AB  - BACKGROUND: Heartburn, a common symptom, is self-treated with oral antacids.
      Efficacy of antacids has not been demonstrated for individual, spontaneous
      heartburn episodes. METHODS: We conducted a double-blind, randomized, placebo
      controlled, parallel-group study of self-directed treatment for episodic
      heartburn comparing famotidine (FAM) 5, 10, or 20 mg and antacid (11 mEq ANC) to
      placebo (PBO) during a 4-week period. Twenty-nine US investigators enrolled a
      total of 565 outpatients, ages 18--81 years (mean 44.1 years) with heartburn but
      not seeking care for heartburn. Treatment of spontaneous heartburn episodes was
      permitted as needed, up to twice daily, with self-administered test drug. An open
      label, backup antacid was provided to use if test drug did not provide adequate
      relief. Patients assessed heartburn relief hourly and recorded use of backup
      antacid. Relief was defined as complete relief of symptoms without the use of
      backup antacid. RESULTS: The media proportion of episodes relieved was: PBO, 41%;
      FAM 5 mg, 59%, 0.05 less-than-or-equal p < 0.10; FAM 10 mg, 70%, p < 0.001; FAM
      20 mg, 69%, p < 0.001; antacid, 62%, p < 0.05 (p-values versus PBO). Supplemental
      analyses incorporating time to relief confirmed that famotidine and antacid
      provided more rapid and more frequent relief than placebo (odds ratio for relief
      relative to PBO: FAM 5 mg, 1.55, p = 0.003; FAM 10 mg, 1.94, p < 0.001; FAM 20
      mg, 2.13, p < 0.001; antacid 1.57, p = 0.003). The tolerability profile was
      similar with famotidine, antacid, and placebo. CONCLUSIONS: The positive results
      with antacid demonstrated for the first time the efficacy of antacid in self
      treatment of individual heartburn episodes and provided internal validation of
      this study paradigm. Patients in this study self-medicated effectively using low
      doses of famotidine on an as needed basis for spontaneous episodes of heartburn.

PMID- 11850669
TI  - Efficacy and Tolerability of Famotidine in Preventing Heartburn and Related
      Symptoms of Upper Gastrointestinal Discomfort.
AB  - This randomized, double-blind, placebo-controlled, four-way crossover trial was
      designed to compare the efficacy of famotidine and placebo in preventing meal
      provoked upper gastrointestinal symptoms. One hundred twenty-one subjects (58 men
      and 63 women), aged 20--61 years, were randomly assigned to one of four treatment
      sequences which included single oral doses of placebo, famotidine 5 mg,
      famotidine 10 mg, and famotidine 20 mg, spaced approximately 7 days apart. To be
      eligible for randomization, subjects had to have at least a 2-month history of
      heartburn and acid/sour stomach occurring at least three times per week.
      Treatment was administered 1 h prior to ingestion of test meals (chili and wine).
      Rescue antacid medication (Maalox((R))) was available for subjects who required
      additional relief. Heartburn severity. acid/sour stomach, and overall discomfort
      were evaluated on a six-point scale immediately prior to each test meal and every
      15 min thereafter for 5 h. A global evaluation of the test medication, using a
      five-point scale, was performed prior to rescue medication use or at the end of
      each treatment session. Heartburn and peak acid/sour stomach were rated as
      significantly milder following prophylactic treatment with famotidine 5, 10, and
      20 mg compared to placebo. Treatment with all three doses of famotidine was rated
      as "good" or "excellent" by significantly more subjects (58--63%) than following
      treatment with placebo (38%). In addition, rescue medication was used by
      significantly fewer subjects following famotidine (17--18%) compared to placebo
      (37%). Famotidine was generally well tolerated in this trial, with type and
      frequency of reported adverse experiences similar to that observed following
      placebo. These results indicated that famotidine doses of 5, 10, and 20 mg were
      significantly more effective than placebo in preventing symptoms of upper
      gastrointestinal distress when administered 1 h in advance of meal provocation.

PMID- 11850670
TI  - Pharmacokinetics and Pharmacodynamics of Recombinant Human Insulin-Like Growth
      Factor.
AB  - Recombinant human insulin-like growth factor (rhIGF-I) was evaluated in 18
      healthy males to determine its effects on serum glucose, its relationship of
      total IGF levels to serum glucose response and dose proportionality when
      administered intravenously (IV) and subcutaneously (SQ). One group of six
      subjects received 60, 120, and 180 &mgr;g kg(minus sign1) IV over 8 h, 1 week
      apart, and three groups of four subjects received 60, 120, and 180 &mgr;g
      kg(minus sign1) IV over 8 h, and then 1 week later received 60, 120, and 90
      &mgr;g kg(minus sign1) SQ of rhIGF-I, respectively. During each dosing period,
      placebo and then rhIGF-I was administered on two consecutive days. Intravenous
      and subcutaneous does of rhIGF-I demonstrated significant decreases in glucose
      levels as compared to placebo that did not correspond to peak total IGF levels.
      Sequential repeat administration of IV infusions of rhIGF-I in a single group of
      subjects demonstrated significant dose-dependent increases, whereas single
      administration of the doses in three groups of subjects failed to demonstrate
      dose dependency for either the IV or subcutaneous routes of administration. These
      findings suggest that saturation of the binding proteins and sites occurred at
      the lowest dose (60 &mgr;g kg(minus sign1)) evaluated.

PMID- 11850671
TI  - Efficacy and Safety of Ramipril in Hypertensive Single-Kidney Patients.
AB  - The effects of medium-term antihypertensive treatment with the ACE inhibitor
      ramipril were studied on 10 hypertensive single-kidney patients in a double-blind
      study versus placebo. Patients with renovascular hypertension were excluded.
      Compared to placebo, ramipril induces a significant reduction of arterial blood
      pressure (p < 0.02 for systolic, p < 0.01 for diastolic, and p < 0.05 for mean
      blood pressure), renal vascular resistance (p < 0.005), and microalbuminuria (p <
      0.005), but a significant rise of effective renal plasma flow (p < 0.01) and no
      significant variation of the glomerular filtration rate. The reduction of
      microalbuminuria was not related to arterial blood pressure variation. Our study
      shows that ramipril, in appropriately selected-kidney patients, is effective and
      safe in reducing arterial blood pressure, bringing about an improvement of renal
      function and reducing microalbuminuria, which is frequently observed in this
      condition.

PMID- 11850673
TI  - Developing Anti-Coagulants for Ischemic Heart Disease.

PMID- 11850672
TI  - The Fourth International Symposium on Cardiovascular Drug Development: Developing
      Drugs for Ischemic Heart Disease---Introduction.

PMID- 11850674
TI  - Regulatory Considerations in Restenosis Trials.

PMID- 11850675
TI  - The Biology of Restenosis and the Use of Low Molecular Weight Heparins.

PMID- 11850676
TI  - Estrogens in Coronary Artery Disease: Regulatory Concerns.

PMID- 11850677
TI  - Panel Discussion.

PMID- 11850678
TI  - Quantitative EEG Brain Mapping In Psychotropic Drug Development, Drug Treatment
      Selection, and Monitoring.
AB  - Quantification of standard electroencephalogram (EEG) by digital computers
      [computer-analyzed EEG (CEEG)] has transformed the subjective analog EEG into an
      objective scientific method. Until a few years ago, CEEG was only used to assist
      in the development of psychotropic drugs by means of the quantitative pharmaco
      EEG. Thanks to the computer revolution and the accompanying reductions in cost of
      quantification, CEEG can now also be applied in psychiatric practice. CEEG can
      assist the physician in confirming clinical diagnoses, selecting psychotropic
      drugs for treatment, and drug treatment monitoring. Advancements in
      communications technology allow physicians and researchers to reduce the costs of
      acquiring a high-technology CEEG brain mapping system by utilizing the more
      economical telephonic services.

PMID- 11850679
TI  - A New Virus and the Adequacy of Public Health Methods.

PMID- 11850680
TI  - A Double-Blind, Randomized Comparison of Aztreonam Plus Clindamycin with
      Tobramycin Plus Clindamycin in Abdominal Infections.
AB  - Seventy patients with intraabdominal infections were randomly assigned in double
      blinded fashion to receive either the combination of tobramycin plus clindamycin
      (TM/C) or aztreonam plus clindamycin (AZ/C). Thirty-four patients received AZ/C
      and 36 were given TM/C. Average ages were 62 years (TM/C) and 66 years (AZ/C). In
      approximately one-half of both groups, the source of infection was perforated
      colon or perforated appendix. There were no significant differences in
      demographic factors between these groups, although those given AZ/C had a more
      serious long-term prognosis due to underlying diseases. The average lengths of
      treatment were 10 days (TM/C) and 9 days (AZ/C). Clinical response to therapy did
      not differ, as 84% of the TM/C patients and 78% of the AZ/C patients had
      satisfactory clinical responses. The two regimens differed in adverse effects, as
      an elevated PT/PTT was more frequently (p < 0.05) observed in AZ/C. All PT/PTT
      elevations responded to injections of vitamin K, and no serious bleeding
      occurred. Choice between these regimens depends on differences in cost and the
      risk of adverse effects, as both regimens appear equally effective for treatment
      of abdominal infections in conjunction with appropriate surgical intervention.

PMID- 11850681
TI  - Renin Status in Association with Responsiveness to Behavioral Therapy in
      Hypertension.
AB  - This double-blind experiment tested the hypothesis that renin is a mediator of
      neurogenic hypertension. Forty-three of 46 hypertensive (mean BP 142/94) were
      typed for renin index and treated by combinations of group therapy (n = 32) or
      placebo (n = 11). A treatment effect in the therapy group resided virtually in
      the high/normal renin subset (21 subjects, mean drop 6/6 mm Hg, p <.05/ <.02),
      and was not present in the low renin subset (11 subjects, mean change minus
      sign3/1 mm Hg). The renin index fell in the high/normal therapy subset of the
      whole therapy group (from mean 217 to 159) while that of the low renin subset
      rose (mean 35 to 85) p, < 0.01. Results show that renin-driven essential
      hypertension is a form of neurogenic hypertension and is susceptible to
      behavioral therapeutic approaches. In this regard, it warrents further study for
      clinical recognition for early application of angiotensin inhibiters and beta
      adrenergic blockade.

PMID- 11850682
TI  - Effect of Domperidone on the Bromocriptine-Induced Antihypertensive Action in
      Hypertensive Patients.
AB  - Dopaminergic receptors have been involved in the cardiovascular and renin
      angiotensin systems (RAS). We have recently reported that bromocriptine is an
      effective antihypertensive drug by stimulating DA(2) dopaminergic receptors.
      However, the nature of the dopaminergic receptors in RAS has not been
      established. Ten outpatients with essential hypertension were treated at the
      Vargas Hospital with bromocriptine (BR) (11.25 mg day(minus sign1)), a DA(2)
      dopaminergic agonist, for a 2-week period, after which an oral dose of 30 mg
      day(minus sign1) of domperidone (DO), a peripheric DA(2) dopaminergic antagonist,
      was added for 2 additional weeks. The active period was preceeded by a 2-week
      placebo period. Bromocriptine decreased blood pressure (BP) significantly by 19/9
      mm Hg (systolic/diastolic BP). Bromocriptine did not cause heart rate (HR)
      changes. Bromocriptine decreased plasma aldosterone (ALD) without altering plasma
      renin activity (PRA). Domperidone partially blocked bromocriptine-induced
      antihypertensive submaximal treadmill effects and reversed ALD decrease. Exercise
      response was not significantly altered by BR + DO. We conclude the following: (1)
      BR is an effective antihypertensive agent; (2) BR seems to be acting at both the
      central and peripheric nervous systems, and (3) the nature of the dopaminergic
      receptor involved in renin secretion does not seem to be DA(2).

PMID- 11850683
TI  - Effects of Enalaprilat on Regional Wall Stress in Patients with Angina Pectoris.
AB  - Left ventricle (LV) cineventriculograms silhouettes in the right anterior oblique
      projection with simultaneous pressure micromanometry were assessed before and 10
      min after administration of 1.25 mg enalaprilat intravenously to 10 patients with
      angina pectoris undergoing diagnostic cardiac catheterization.
      Cineventriculograms were divided into 20 areas using a modified Leighton's method
      for segmentalization of the LV and computed by the Janz's method for regional
      wall stress. Enalaprilat reduced preload and afterload in all cases. There was
      significant reduction in regional wall stress in 15 of the 20 segments after
      enalaprilat administration compared with baseline analysis. Segments without
      significant reduction in wall stress wee apical. There was significant reduction
      in global wall stress after enalaprilat. Thus, enalaprilat, in addition to
      improve hemodynamics decreasing both preload and afterload, reduces LV wall
      stress both regional and global. Clinical implications of these findings are in
      agreement with the wall stress reduction for prevention of ventricular remodeling
      with this agent in postinfarction patients.

PMID- 11850684
TI  - Efficacy and Safety of Evening Administration of Controlled-Delivery Diltiazem
      Capsules in Chronic Stable Angina Patients.
AB  - The safety and efficacy of controlled-delivery (CD) once-a-day formulation of
      diltiazem administered in the evening, at a dose of 240 mg, was assessed in 37
      patients with stable angina pectoris. A double-blind, placebo-controlled,
      randomized, crossover protocol was used. Following a 4-day washout period,
      patients entered a 5--7-day single-blind placebo run-in period during which
      qualification and reproducibility exercise treadmill tests (ETTs) were performed
      24 h postdose. Eligible patients were randomized in a double-blind fashion, to
      either CD diltiazem or to placebo for a 7--10-day treatment period. They then
      entered a 5--7-day single-blind washout period, after which they received the
      alternate treatment for another 7 to 10 days. ETTs were performed at the end of
      each treatment period. Compared to placebo, evening administration of CD
      diltiazem produced a marked improvement of the time to ETT termination, time to
      onset of angina, and time to 1 mm ST depression. In addition, the number of
      angina attacks recorded in patient diaries was reduced compared to placebo.
      Incidence of adverse events was comparable with CD diltiazem and placebo. We
      conclude that evening administration of controlled-delivery diltiazem is highly
      effective and safe in the treatment of stable angina pectoris.

PMID- 11850685
TI  - Lack of Pharmacokinetic Interaction between Aspirin and Warfarin.
AB  - An open-label, randomized, two-phase crossover study was conducted on 36 healthy
      male volunteers to identify the effects of coadministration of aspirin
      (acetylsalicylic acid; ASA) and crystalline warfarin sodium (Coumadin((R))) on
      the elimination and disposition kinetics of ASA, salicylic acid (SA) and R- and S
      warfarin enantiomers. Twenty-four subjects were administered single doses of 325
      mg of ASA alone and in combination with 10 mg of crystalline warfarin sodium with
      a 1-week washout between ASA doses. ASA and SA pharmacokinetic parameters were
      determined after each dose. Twelve subjects were administered single doses of 10
      mg of crystalline warfarin sodium alone and in combination with 325 mg of ASA
      with a 4-week washout between warfarin doses. R- and S-warfarin enantiomer
      pharmacokinetic parameters were determined after each dose. Pharmacokinetic
      parameters were compared using analysis of variance and 90% confidence intervals.
      ASA and SA AUCs (the area under the plasma concentration versus time curve from
      time zero to time infinity) respectively were 3.28 plus minus 0.80 and 66.99 plus
      minus 11.73 &mgr;g h ml(minus sign1) (ASA alone), and 3.22 plus minus 0.61 and
      69.48 plus minus 15.79 &mgr;g h ml(minus sign1) (ASA with warfarin). R-warfarin
      and S-warfarin AUCs respectively were 33.9 plus minus 9.3 and 23.9 plus minus
      16.0 &mgr;g h ml(minus sign1) (warfarin alone) and 33.6 plus minus 10.2 and 22.6
      plus minus 14.7 &mgr;g h ml(minus sign1) (warfarin with ASA). The only
      pharmacokinetic parameter which was statistically significantly different when
      the combination was administered was the S-warfarin elimination rate constant (p
      < 0.05), but the difference (9.2% increase in the presence of ASA) was small and
      no significant difference was found in S-warfarin clearance. It is concluded that
      there is no pharmacokinetic interaction when a single dose of ASA 325 mg is
      coadministered with a single dose of crystalline warfarin sodium 10 mg.

PMID- 11850686
TI  - Simulations of Levothyroxine Bioavailability Using a Single-Dose Study Protocol.
AB  - Computation of oral levothyroxine bioavailability parameters is hampered due to a
      long pharmacokinetic half-life and the secretion of endogenous levothyroxine
      hormone. To overcome these difficulties, Berg and Mayor (J Clin Pharmacol 1992;
      32: 1135--1140) suggested the use of a single, supraphysiologic levothyroxine
      oral dosage protocol and measurement of levothyroxine area under the serum
      concentration versus time curves (AUC) for 48 h after dose administration. Since
      this protocol is a nonstandard methodology, simulations were performed to assess
      potential errors associated with the proposed method. The pharmacokinetic
      simulations indicate a potential methodological error of about 1% in AUC
      computations. However, for patients with extremely short levothyroxine half-lives
      (<2--3 days), larger errors in AUC values are possible.

PMID- 11850687
TI  - Limitations of Levothyroxine Bioequivalence Evaluation: Analysis of An Attempted
      Study.
AB  - The relative bioavailability and therapeutic comparability of four levothyroxine
      products (two proprietary and two nonbranded) were determined in an open-label,
      block-randomized, four-way crossover trial with no washout periods in 24 presumed
      hypothyroid ambulatory care patients who were considered euthyroid while on 100
      &mgr;g or 150 &mgr;g of oral levothyroxine daily for at least 3 months. Patients
      randomly received each of the four levothyroxine products for 6 weeks at the same
      dosage as their prestudy regimen. Area under the serum concentration versus time
      curve (AUC), maximum change in serum concentration (C(max)), and time to peak
      serum concentration (T(max)) were calculated for total thyroxine (TT(4)), total
      triiodothyronine (TT(3)), free thyroxine index (FT(4)I), and thyrotropin (TSH)
      for each product, with and without baseline correction and normalization for
      tablet potency differences. Ninety-percent confidence intervals were determined
      for each paired treatment comparison. Using the response variable of values
      uncorrected for baseline (Hour 0), 90% confidence intervals for paired treatment
      comparisons of nonlogarithmically transformed AUC and C(max) (TT(4), TT(3), and
      FT(4)I) were within the range of 80% to 120%. However, using the response
      variable of baseline corrected values, no confidence intervals for TT(4) or TT(3)
      AUC or TT(3) C(max) were within the range of 80% to 120%. Confidence intervals
      for TSH AUC and C(max) based on both baseline corrected and uncorrected values
      were outside the 80--120% range. Results were similar when AUC and C(max) were
      normalized for tablet potency. Thus, results both within and between response
      variables were conflicting. Further, results normalized for potency using either
      response variable also failed to demonstrate bioequivalence, pointing to the
      serious difficulties inherent in levothyroxine bioequivalence studies.
      Independent consultant review of study design, execution, and data analysis was
      used to identify critical issues in the conduct of future levothyroxine
      bioequivalence studies. Numerous flaws were identified, including many that could
      significantly impact the interpretation of results. These flaws included
      evaluation of a heterogeneous population of hypothyroid patients with variable
      residual thyroid function, failure to achieve steady-state serum thyroid hormone
      levels, use of levothyroxine preparations with variable and unmatched potency,
      calculations based on a response variable that requires linear pharmacokinetics,
      and application of bioequivalence criteria when required assumptions have not
      been met. By the criteria applied in this study and using a response variable
      based on uncorrected serum concentrations, the levothyroxine products studied,
      although appearing to be bioequivalent, were, in fact, therapeutically
      inequivalent. Yet, using an equally accepted and perhaps more valid response
      variable of baseline corrected values, this study failed to demonstrate
      bioequivalence between any two products. Finally, differences in tablet potency
      must be considered as contributing to the appearance of bioequivalence for the
      TT(4) comparisons. For these reasons, this study, as well as others based on
      similar models, cannot support a recommendation to substitute levothyroxine
      products without careful retesting and retitration. The basis for this position
      is that interchange of therapeutically inequivalent products may result in over-
      or under-replacement of thyroid hormone, with the known potential adverse
      consequences. From an economic perspective, product interchange may lead to
      additional medical costs that outweigh the initial savings obtained by the
      product switch.

PMID- 11850688
TI  - Drug Interactions: Classification and Systematic Approach.
AB  - Interactions between drugs may result in favorable, toxic or no clinical effects.
      Generally classified in terms of proposed mechanism, drug interactions may be
      causal to physicochemical incompatibility, pharmacokinetic or pharmacodynamic
      interaction(s), combinations of each. Characterized by alterations in circulating
      unbound (tree) drug or its principal metabolic, pharmacokinetic interactions are
      secondary to modification(s) in absorption, volume of distribution, metabolism or
      excretion. Synergism, defined as two or more drugs acting upon receptor site(s)
      to produce additive or superadditive effects, or antagonism, defined by a
      shifting of the dose-response curve to the right indicating a diminution of
      effect after stimulation of a receptor site are pharmacodynamic interactions
      occurring without demonstrable alteration in plasma levels of the drugs. This
      article reviews these various types and mechanisms of drug interactions.

PMID- 11850689
TI  - Proarrhythmia or Arrhythmogenicity.

PMID- 11850690
TI  - Cardiovascular and Hormonal Effects of Domperidone, A Peripheral Dopaminergic
      Blocker, in Bromocriptine-Treated Hypertensive Patients.
AB  - Nine patients with mild or moderate essential hypertension were studied at the
      Vargas Hospital of Caracas, Venezuela. After antihypertensive treatment
      discontinuation, all patients were placed on placebo during a 1-week period,
      after which domperidone, a peripheral DA(2) dopaminergic blocker, was orally
      administered at the dose of 20 mg every 12 h during a period of 1 week. A final 1
      week period of bromocriptine, 2.5 mg orally every 8 h, followed the domperidone
      period. Cold pressor test caused an increase of mean blood pressure and of heart
      rate, which was more accentuated after adding bromocriptine. Domperidone also
      caused an increase of serum aldosterone levels. Our results suggest that a
      dopaminergic mechanism is acting during the cold pressor test and during
      aldosterone secretion.

PMID- 11850691
TI  - Large-Scale Postmarketing Surveillance of Hypertensive Patients Treated with
      Verapamil.
AB  - BACKGROUND: In general clinical practice, physicians prescribe calcium channel
      blockers to a wide range of patients with differing demographic characteristics
      and hypertension history. This study was undertaken to investigate the
      effectiveness and safety of sustained-release verapamil (Verelan((R)), verapamil
      HCl) in patients with essential hypertension, studied under "usual use"
      conditions. METHODS: In this prospective, open-label, postmarketing surveillance
      study, 25 089 patients with hypertension received once-daily verapamil therapy
      for 4 weeks, during which they were evaluated by 8106 physicians at baseline and
      at two follow-up visits (weeks 2 and 4). In this study, hypertension was defined
      as an average sitting diastolic blood pressure (DBP) of greater-than-or-equal 90
      mm Hg at baseline. Previously diagnosed hypertensive patients with a sitting DBP
      <90 mm Hg but experiencing untoward effects requiring discontinuation of current
      antihypertensive therapy were also included. RESULTS: Eighty-five percent (n = 21
      446) of the total patients enrolled at baseline completed this office-based
      trial. Nearly 24% of patients were newly diagnosed hypertensives. At baseline,
      the mean systolic blood pressure (SBP) and diastolic blood pressure were 161 and
      96 mm Hg, respectively. In evaluable patients with mild, moderate, and severe
      hypertension, as stratified by baseline measurements, treatment with verapamil
      produced DBP reductions of 12, 19, and 29 mm Hg, respectively. Verapamil
      treatment produced clinically similar SBP, DBP, and HR (heart rate) reductions
      across gender and racial groups studied (white, black, Hispanic, and Asian). Only
      6.1% of patients failed to complete the study because of any reported adverse
      experiences (4.5% of patients discontinued because of adverse experiences
      considered drug related). Constipation (5.0%) and headache (1.1%) were the most
      commonly reported adverse events. CONCLUSION: In general clinical practice,
      verapamil is well tolerated and effective in a broad range of hypertensive
      patients.

PMID- 11850692
TI  - Nomega-Nitro-L-Arginine Benzyl Ester Enhances Pulmonary Vasopressor Responses to
      Hypoxia and to Angiotensin II.
AB  - The effects of Nomega-nitro-L-arginine benzyl ester (L-NABE), an inhibitor of
      nitric oxide (NO) synthase, were investigated on pulmonary arterial responses
      during baseline or low tone conditions and during elevated tone conditions
      induced by ventilatory hypoxia or by AII in the isolated blood-perfused rat lung.
      We also tested the influence L-NABE on the vasodilator responses to acetylcholine
      (ACh) and nitroglycerin (GTN) during elevated pulmonary arterial tone conditions.
      Under baseline conditions, L-NABE in doses of 10--1000 &mgr;g, induced small
      increases in pulmonary arterial perfusion pressure that were significant for the
      higher doses studied. Ventilation with an hypoxic gas mixture or administration
      of AII significantly increased pulmonary arterial perfusion pressure and the
      responses were reproducible with respect to time. Following administration of L
      NABE, the pulmonary arterial responses to hypoxic ventilation (HPV) were
      significantly enhanced, and L-NABE significantly enhanced the pulmonary arterial
      pressor responses to angiotensin II. During elevated pulmonary arterial tone
      conditions induced with hypoxic ventilation, L-NABE inhibited the vasodilator
      responses to acetylcholine (ACh); however, the vasodilator responses to
      nitroglycerin (GTN) were not altered. The small effect of L-NABE on baseline
      pulmonary arterial pressure in the isolated blood-perfused rat lung suggests that
      NO plays only a small role in maintaining pulmonary vascular tone at low resting
      levels. However, the augmentation of the pressor responses by L-NABE during HPV
      and to AII suggests that NO plays an important role in modulating these pulmonary
      pressor responses during elevated tone conditions. Additionally, the inhibition
      of pulmonary vasodilator response to ACh supports the hypothesis that NO release
      plays a major role in mediating vasodilator responses to endothelial-dependent
      agents such as ACh, but not to endothelial-independent agents such as GTN. In
      conclusion, these data suggest that NO release is more important under stimulated
      conditions than under basal conditions.

PMID- 11850693
TI  - Ibopamine in Patients with Congestive Heart Failure and Different Degrees of
      Renal Function.
AB  - Following a 1-week placebo run-in phase, 20 patients with congestive heart
      failure (New York Heart Association class II) were treated orally for 7 days with
      100 mg ibopamine t. i. d. Ten subjects had a normal renal function, whereas 10
      patients suffered from chronic renal insufficiency (mean creatinine clearance 36
      plus minus 3.9 ml min(minus sign1)). Ibopamine significantly increased stroke
      volume and cardiac output, but only 45 and 90 min after administration. After 7
      days of ibopamine treatment, urine output rose significantly in both patient
      groups by about 400--500 ml per 24 h. The glomerular filtration rate (inulin
      clearance) and urine osmolality remained nearly unchanged, whereas renal plasma
      flow (PAH clearance) increased on ibopamine administration. Urinary sodium and
      potassium excretion were slightly but insignificantly elevated. Pharmacokinetic
      parameters of ibopamine were unaltered in impaired renal function, both on the
      first and seventh treatment day. Maximum plasma levels of the active metabolite
      epinine were achieved after 45 min and were higher on the first as compared with
      the seventh treatment day in both groups. In conclusion, ibopamine caused a
      relevant increase in stroke volume and cardiac output associated with a rise in
      renal perfusion and urine output in patients with normal and with impaired renal
      function. Ibopamine is an orally active derivative of dopamine and is used for
      treatment of patients with congestive heart failure, who frequently have an
      impaired renal function. Therefore, in the present study, the hemodynamic effects
      and kinetic behavior of ibopamine should be investigated in patients with
      different degrees of renal function.

PMID- 11850694
TI  - Low-Dose Aspirin and Ibuprofen Reduce the Cutaneous Reactions Following Niacin
      Administration.
AB  - BACKGROUND: Moderate doses of prostaglandin inhibitors may reduce the cutaneous
      reactions from niacin administration. We undertook this study to determine if low
      doses of either ibuprofen or aspirin reduces cutaneous reactions from niacin in
      healthy volunteers. METHODS: Twenty-two subjects were randomized to received
      crystalline niacine 500 mg preceded by either placebo, aspirin 165 mg, aspirin
      325 mg, or ibuprofen 200 mg. The study was crossover and double blinded, and
      treatment arms were separated by 2 days. Subjects were asked to rate the severity
      of flushing, itching, and tingling after niacin on a visual analog scale (0---no
      symptoms; 10---severe symptoms). Statistical analysis was performed using
      repeated measures of analysis of variance. RESULTS: Nineteen of the 22 subjects
      completed the protocol. Overall, aspirin 325 mg statistically reduced flushing
      after niacin administration. No statistical difference was observed for the other
      treatment arms for either flushing, itching, or tingling. When subjects
      experiencing the worse symptoms were analyzed separately, all treatment arms
      statistically reduced the flushing, itching, or tingling from niacin. Aspirin 325
      mg was the most efficacious, followed by aspirin 165 mg and ibuprofen 200 mg.
      CONCLUSION: These data demonstrate that pretreatment with low doses of aspirin or
      ibuprofen are effective in reducing cutaneous reactions from niacin
      administration.

PMID- 11850695
TI  - Comparative Effects of Liquid Antacids on Esophageal and Gastric pH in Patients
      with Heartburn.
AB  - This double-blind crossover trial compared the postmeal effects of single doses
      of liquid antacids on esophageal and gastric pH in patients with a history of
      heartburn. Treatment consisted of one of two antacids containing the same active
      components---aluminum and magnesium hydroxide---but different in vitro acid
      neutralizing capacities (ANCs). The pH was assessed continually from 1 h before a
      refluxogenic meal to 4 h after its completion in 24 subjects who received 20 ml
      of Mylanta((R)) Double Strength (MYL-20: ANC = 101.6 mEq), 20 or 30 ml of Extra
      Strength Maalox((R)) Plus (MA-20, MA-30: ANC = 116.2 and 174.3 mEq,
      respectively), or placebo (ANC = 0) in random order. Esophageal pH increased
      rapidly and significantly (p < 0.05) to peak values of 7.0--7.4 with antacid. The
      increase in mean esophageal pH values was significantly higher (p < 0.05) than
      placebo for 30 min with MA-20 and for at least 70 min with MYL-20 and MA-30. In
      contrast, gastric pH rose slowly to mean peaks of 2.9--3.1 with antacid. During
      this interval, only MYL-20 was associated with significant improvements (p < 0.05
      versus placebo) in total number of reflux episodes and total time that esophageal
      pH measured >4. Thus, ANC alone is not a useful guide in predicting in vivo
      antacid behavior, as in this study where the antacid dose with the lowest ANC
      demonstrated a duration of action as long or longer than that of antacid doses
      with higher ANC values. The rapid, prolonged increases in esophageal pH that
      preceded modest changes in gastric pH strongly suggest that the lower esophagus
      is the primary site of antacid action for heartburn relief.

PMID- 11850696
TI  - Treatment of Khat Addiction with Bromocriptine Mesylate: A Case Report and Review
      of Cocaine- and Amphetamine-Like Effects.
AB  - A patient addicted to khat was successfully treated as an outpatient. He was
      detoxified with bromocriptine mesylate 1.25 mg. q 6 h which was titrated downward
      over 4 weeks. Khat is a bush historically indigenous to the Mideast. It has high
      addictive potential due to its constituent, "cathinone." Cathinone, (1(5) +
      (minus sign) aminopropiophenon), is a sympathomimetic, similar but not identical
      to cocaine and amphetamine in activity and addiction potential. Bromocriptine has
      been extensively reported to successfully detoxify cocaine addiction and could be
      useful in khat addiction.

PMID- 11850697
TI  - The Influence of Dirithromycin on the Pharmacokinetics of Cyclosporine in Healthy
      Subjects and in Renal Transplant Patients.
AB  - The effect of a standard regimen of the investigational macrolide antibiotic,
      dirithromycin, on the single-dose kinetics of orally administered cyclosporine
      (CSA) was investigated in healthy young males and on the steady-state disposition
      kinetics of cyclosporine in a panel of renal transplant patients. Eight male
      volunteers participated after giving informed consent. CSA was administered in
      three single doses (15 mg kg(minus sign1) p.o. each) in each of three phases: (1)
      prior to a 14-day regimen of dirithromycin; (2) at the end of a 14-day regimen of
      dirithromycin (500 mg p.o. qAM); and (3) 2 weeks after the last dose of a 14-day
      regimen of dirithromycin. Pharmacokinetic parameters of CSA were estimated, and
      the differences among treatments were assessed by analysis of variation. No
      significant differences among treatment (phase) means were detected (p < 0.05).
      We conclude that a typical 14-day regimen of dirithromycin failed to alter the
      disposition kinetics of CSA when taken orally healthy young adult males. The
      effect of a standard regimen of dirithromycin on the steady-state disposition
      kinetics of orally administered CSA was investigated in a panel of 15 stable
      renal transplant patients. Pharmacokinetic parameters for CSA were evaluated
      prior to, during, and 2 weeks after discontinuing a 14-day (500 mg day(minus
      sign1)) oral regimen of dirithromycin. Dirithromycin elicited small but
      significant changes in the following parameters: C(av) was increased by 16%
      during dirithromycin treatment, and the changes in normalized C(av) were
      comparable. Likewise, C(SS,min) and normalized C(SS,min) were increased by 19%
      and 20%, respectively, during dirithromycin treatment. CSA oral clearance,
      CL/F(SS), decreased by 17% during dirithromycin treatment. C(SS,max) and
      normalized C(SS,max) were increased by 13% and 17%, respectively, during
      dirithromycin treatment but were not significantly different from those either
      before or after dirithromycin. The magnitude of the pharmacokinetic changes for
      CSA during dirithromycin treatment (<15% in normal subjects and 15--20% in renal
      transplant patients) when considered in the context of the therapeutic range of
      cyclosporine concentrations was relatively small, and not likely to warrant
      special attention to the dosing of CSA in such patients beyond routine whole
      blood CSA and serum creatinine monitoring.

PMID- 11850698
TI  - Effect of Food on the Pharmacokinetics and Pharmacodynamics of Torsemide.
AB  - The effect of food on the bioavailability, pharmacokinetics, and pharmacodynamics
      of oral torsemide was examined in a group of 14 healthy male volunteers.
      Administration of torsemide with a standard high-fat, high-carbohydrate breakfast
      resulted in a decrease in absorption rate (fed: C(max) 988 plus minus 269 ng
      ml(minus sign1), T(max) 1.50 plus minus 0.64 h; fasting: C(max) 1466 plus minus
      202 ng ml(minus sign1), T(max) 0.89 plus minus 0.37 h) but no change in the
      extent of absorption (fed: AUC 3424 plus minus 841 h ng ml(minus sign1); fasting:
      AUC 3357 plus minus 859 h ng ml(minus sign1)) or the amount of drug excreted
      unchanged (fed: % dose 23.5 plus minus 4.3; fasting: % dose 23.7 plus minus 6.2).
      Elimination half-life and renal clearance were unchanged. These minor alterations
      in the pharmacokinetics of the drug were not reflected by a change in either the
      pharmacodynamic relationship between urinary sodium and drug excretion rates or
      the cumulative amount of electrolytes and urine excreted. The diuretic effect of
      torsemide will be consistent regardless of drug administration relative to food
      intake.

PMID- 11850699
TI  - Pharmacokinetics of Loratadine in Pediatric Subjects.
AB  - The pharmacokinetics of loratadine, a new nonsedating antihistamine, was studied
      in 14 pediatric volunteers between the ages of 8 to 12 years. In an open-label
      design, one volunteer (with body weight less than 30 kg) received 5 mg of
      loratadine syrup and 13 volunteers (with body weights greater than 30 kg)
      received 10 mg of loratadine syrup. Blood samples were collected up to 72 h after
      dosing. Plasma concentrations of loratadine and its metabolite,
      descarboethoxyloratadine, were determined by a specific and sensitive gas-liquid
      chromatographic method. Following a 10-mg dose as a syrup, plasma concentrations
      of loratadine and descarboethoxyloratadine could be determined up to 8 and 48 h,
      respectively. The maximum concentration (C(max)) of loratadine and
      descarboethoxyloratadine were approximately 4 ng ml(minus sign1) each. However,
      the AUC of the metabolite was about six times that of loratadine. The elimination
      phase half-life of descarboethoxyloratadine averaged about 13.8 hr. The
      pharmacokinetics of loratadine in pediatric subjects was similar to that in
      healthy adult volunteers.

PMID- 11850700
TI  - Profiling Antihypertensive Therapy.
AB  - The objectives of treating hypertension are to achieve adequate control of blood
      pressure (BP) and maintain it under tight control. Maintenance of tight control
      of BP will most likely prevent stroke, heart attack, and heart failure, cause
      regression of left ventricular hypertrophy, and quite possibly preserve or
      improve renal function. The last two salutary effects combined will further
      reduce the morbidity and mortality in the treated hypertensive subjects. Choice
      of antihypertensive drugs is of significant importance so that our efforts to
      control hypertension do not grossly alter the quality of life. The cost of
      therapy is also an important consideration. Thus, thiazide diuretics, beta
      blockers, and central inhibitors that are relatively inexpensive and adequately
      lower BP should be a common choice. However, if drowsiness interferes with work,
      or impotence becomes a threat for the marital partner or significant other,
      adjustment has to be made. The metabolic abnormalities consisting mainly of
      impaired glucose tolerance, hypercholesterolemia, and insulin resistance often
      induced by these relatively inexpensive drugs have put calcium channel blocker
      and ACE inhibitor group of drugs on the top of the list for antihypertensive
      therapy. They are far more expensive, yet offer no greater antihypertensive
      advantage than a diuretic or central inhibitor, except in special circumstances.

PMID- 11850701
TI  - Transplant-related toxicity and mortality: an AIEOP prospective study in 636
      pediatric patients transplanted for acute leukemia.
AB  - Hematopoietic stem cell transplantation can cure high-risk acute leukemia (AL),
      but the occurrence of non-leukemic death is still high. The AIEOP conducted a
      prospective study in order to assess incidence and relationships of early
      toxicity and transplant-related mortality (TRM) in a pediatric population.
      Between 1990 and 1997 toxicities reported in eight organs (central nervous
      system, heart, lungs, liver, gut, kidneys, bladder, mucosa) were classified into
      three grades (mild, moderate, severe) and prospectively registered for 636
      consecutive children who underwent autologous (216) or allogeneic (420)
      transplantation, either from an HLA compatible related (294), or alternative
      (126) donor in 13 AIEOP transplant centers. Overall, 47% of the patients are
      alive in CR (3-year EFS: 45.2%, s.e.: 2.1), 19% died in CR at a median of 60 days
      (90-day TRM: 14.3%, s.e.: 1.4), 34% relapsed. Toxicity of any organ, but mucosa
      and gut, was positively correlated with early death; moderate and severe toxicity
      to heart, lungs, liver and kidneys significantly increased early TRM, with
      estimated relative risks of 9.1, 5.5, 2.7 and 2.8, respectively, as compared to
      absent or mild toxicity. Patients with grade III-IV aGVHD experienced more than
      double (56% vs. 19%) TRM than patients with grade 0-II aGVHD. A higher cumulative
      toxicity score, estimating the impact of toxicity on TRM, was significantly
      associated with transplantation from an alternative donor. Quantitative
      assessment allowed us to describe the extent to which 'grade' of toxicity and
      'type' of involved organs were related to mortality and pre-transplant
      characteristics and yielded a prognostic score potentially useful to compare
      different conditioning regimens and predict probability of early death.

PMID- 11850702
TI  - Haematopoietic stem cell transplantation for thalassaemia major in Hong Kong:
      prognostic factors and outcome.
AB  - From August 1992 to August 1999, 44 patients received allogeneic haematopoietic
      stem cell transplantation in a single institution. The donors were HLA-identical
      siblings except for one who was a phenotypically matched father. Thirty-eight
      patients received bone marrow stem cells and the others received peripheral blood
      stem cells or umbilical cord blood (UCB). The mean age at transplant was 10.7+/
      5.1 years, ranging from 1.8 to 21 years. Patients received busulphan (16 mg/kg)
      and cyclophosphamide (150 to 200 mg/kg) as conditioning, and antithymocyte
      globulin was given to 42 patients to prevent graft rejection. All had engraftment
      except a patient who received a UCB transplant. Four patients died from early
      treatment-related mortality, and one died from interstitial pneumonitis 3 months
      after transplant. Two patients developed secondary graft rejection and both
      received a second transplant. Thirty-eight patients survived and all except one
      were transfusion independent. The 5-year overall and event-free survival rates
      were 86% and 82%, respectively. By multivariate stepwise Cox proportional hazard
      analyses, severe veno-occlusive disease (VOD) of liver and Pesaro class 3
      features were the significant factors associated with survival. Patients aged
      more than 11 years were more inclined to develop VOD. In conclusion,
      haematopoietic stem cell transplantation should be performed early if an HLA
      identical sibling is available.

PMID- 11850703
TI  - Enhancement by cyclosporine A and tacrolimus of serotonin-induced formation of
      small platelet aggregation.
AB  - Cyclosporine A (CsA) may increase the incidence of thrombotic events, but whether
      tacrolimus (Tc) has such effects is still unclear. The serotonergic system has
      been linked to the thrombotic effects of CsA, but a direct effect of CsA on
      serotonin-induced platelet aggregation has not been demonstrated because of
      methodological difficulties. We measured the effects of CsA and Tc on serotonin
      induced platelet aggregate formation by particle counting using light scattering.
      CsA and Tc both enhanced serotonin-induced formation of small platelet
      aggregates, however, neither CsA nor Tc affected aggregation induced by high or
      low concentrations of ADP, with or without addition of a serotonin receptor
      antagonist. Both CsA and Tc enhance platelet aggregation induced via the
      serotonin pathway.

PMID- 11850704
TI  - The use of zanamivir to treat influenza A and B infection after allogeneic stem
      cell transplantation.
AB  - The use of zanamivir in seven patients with influenza (three A and four B) post
      allograft is described. Inhaled zanamivir (10 mg twice daily) was continued from
      the diagnosis of influenza until excretion of virus ceased (median duration 15
      days, range 5 to 44 days). There was no toxicity attributable to zanamivir and
      rapid resolution of influenza symptoms was seen. There was no mortality due to
      influenza in the seven patients. The good outcome of 30 previous patients with
      influenza post transplant is described. A randomised multicentre study would be
      required to demonstrate efficacy.

PMID- 11850705
TI  - Palivizumab is highly effective in suppressing respiratory syncytial virus in an
      immunosuppressed animal model.
AB  - Respiratory syncytial virus (RSV) is widely recognized as a leading cause of
      pneumonia, with substantial mortality, in bone marrow transplant recipients. We
      tested the efficacy of a systemic monoclonal antibody (MAB) preparation
      possessing a high titer of anti-RSV neutralizing antibody, palivizumab (Synagis)
      for prophylaxis and therapy of RSV infection in cytoxan (CY) immunosuppressed
      cotton rats, a model in which the efficacy of a polyclonal anti-RSV product
      (Respigam) has been demonstrated. Both prophylaxis and therapy with this MAB were
      highly effective in reducing pulmonary viral replication. However, multiple
      sequential therapeutic doses of MAB were necessary to control rebound viral
      replication in continually suppressed animals.

PMID- 11850706
TI  - Long-term adverse effects on dentition in children with poor-risk neuroblastoma
      treated with high-dose chemotherapy and autologous stem cell transplantation with
      or without total body irradiation.
AB  - Chemo- and radiotherapy may have injurious effects on developing teeth. In this
      long-term follow-up study among poor-risk neuroblastoma (NBL) survivors our aims
      were: (1) to assess both the type and extent of the side-effects of the
      anticancer treatment on tooth development; and (2) to develop an index for
      expressing total damage to the permanent dentition. We studied the dental
      development from panoramic radiographs (PRG) of 18 long-term survivors treated
      under the age of 6 years with high-dose (HD) chemotherapy and autologous stem
      cell transplantation (ASCT) for poor-risk NBL. The myeloablative therapy was
      either HD chemotherapy and fractionated total body irradiation (TBI) of 10-12 Gy
      (TBI group, n = 10) or HD chemotherapy only (non-TBI group, n = 8). A defect
      index (DeI) was developed to describe the damage to the permanent dentition. The
      DeI was also tested in 18 healthy adolescents. All NBL patients had disturbances
      in dental development including short roots, arrested root development,
      microdontia and tooth aplasia. After TBI, 9/10 patients had very severe root
      defects, in contrast to none in the non-TBI group. All children in the TBI group
      had 2-12 (mean 6.6) missing permanent teeth, while 2/5 in the non-TBI group (3/8
      excluded due to young age) had two and four missing permanent teeth,
      respectively. Microdontia was found at equal frequency in both groups. The mean
      value of the DeI was 70.0 (range 28-117) in the TBI group, 15.2 (range 4-34) in
      the non-TBI group (P<0.001, Mann-Whitney U test) and 1.8 (range 0-15) in healthy
      adolescents. Disturbances in dental development may compromise occlusal function
      in poor-risk NBL patients after ASCT, especially when TBI is included in the
      conditioning regimen. Long-term dental follow-up and rehabilitation is required.

PMID- 11850707
TI  - Renal function after autologous bone marrow transplantation in children: a long
      term prospective study.
AB  - We measured glomerular filtration rate (GFR), effective renal plasma flow (ERPF)
      and the concentrating capacity of the kidneys in children after autologous BMT.
      Twenty-six patients had received TBI in their conditioning regimen and 14
      patients had received chemotherapy only. Median follow-up was 10 years. Mean GFR
      before BMT was close to normal in both groups. Mean GFR decreased from 124 [CI
      114,134] ml/min/1.73 m(2) before BMT to 99 [CI 82,115] ml/min/1.73 m(2) 6 months
      after BMT in the + TBI group (P < 0.001). There was no significant change in the 
      TBI group. Mean ERPF before BMT was high: 1110 [95% CI 830,1390] ml/min/1.73 m(2)
      in the + TBI group and 910 [CI 570,1250] ml/min/1.73 m(2) in the - TBI group. Six
      months after BMT, there was a tendency to a decrease in ERPF in the +TBI group,
      to 760 [CI 580,940] ml/min/1.73 m(2) (P = 0.064). After this initial decrease,
      GFR and ERPF remained essentially unchanged in both groups. The mean
      concentrating capacity of the kidneys was normal before and after BMT. In seven
      patients chronic renal impairment developed after BMT (GFR <70 ml/min/1.73 m(2)).
      All had received TBI. They had also received more nephrotoxic antibiotics than
      the other patients. We conclude that TBI was the principal cause of deterioration
      of renal function after BMT, possibly by limiting compensatory hyperperfusion and
      resulting in a fall in GFR. Antibiotic treatment may have contributed.

PMID- 11850709
TI  - Healthy sibling donor anxiety and pain during bone marrow or peripheral blood
      stem cell harvesting for allogeneic transplantation: results of a randomised
      study.
AB  - This study reports the first comparison of healthy donor subjective well-being
      during two alternative procedures of hematopoietic stem cells harvesting for
      allogeneic transplantation. Among the 105 donors included between September 1996
      and October 1998 in the SFGM French randomised trial aiming to compare allogeneic
      bone marrow (BM) transplantation and blood cell (BC) transplantation, 64 donors
      (33 in BC and 31 in BM groups) were relevant for the analysis. They had received
      a set of self-administered questionnaires to complete during the collection
      process, aiming to measure anxiety (assessed using the Spielberger's State-Trait
      Anxiety Inventory) and pain induced by the procedure (evaluated using a visual
      analogical scale). Results showed that no harvest procedure is free from pain
      even if none was more painful than the other. Levels of anxiety before the
      collection procedure were high in both groups and significantly so for BC donors.
      Although BC collection induces at least similar levels of pain and anxiety as
      does BM collection, they were of a different kind, and the short-term impact of G
      CSF stimulation on the well-being of BC donors has to be taken into account in
      improving quality of care in the allogeneic setting.

PMID- 11850708
TI  - A randomized trial of heparin plus ursodiol vs. heparin alone to prevent hepatic
      veno-occlusive disease after hematopoietic stem cell transplantation.
AB  - Hepatic veno-occlusive disease (VOD) is a common and serious regimen-related
      toxicity after hematopoietic stem cell transplantation (HSCT). There is no safe
      and proven therapy for established VOD, and focus has been on its prevention.
      Previous studies have shown that a continuous infusion of unfractionated heparin
      or ursodiol may reduce the incidence of VOD. In order to compare the efficacy of
      heparin plus ursodiol with that of heparin alone, we conducted a prospective,
      randomized study involving 165 consecutive patients who underwent HSCT for a
      variety of disorders. Eighty-two patients were assigned to receive heparin plus
      ursodiol, and 83 were assigned to receive heparin alone. Thirteen and 16 patients
      were diagnosed as having VOD in the heparin plus ursodiol group and the heparin
      alone group, respectively (15.9% vs 19.3%; P = 0.348). Eighty-nine percent of the
      heparin plus ursodiol group and 89.2% of the heparin alone group were surviving
      at day 100 post-HSCT (P = 0.298). The only independent variable associated with
      an increased risk of VOD was an allogeneic type of HSCT (P = 0.018). In
      conclusion, this study shows that there is no difference in efficacy between
      heparin plus ursodiol and heparin alone for the prevention of hepatic VOD.

PMID- 11850710
TI  - A two-phase pathogenesis of graft-versus-host disease in mice.
AB  - Activation of donor T cells is required for the development of graft-versus-host
      disease (GVHD), a major complication of bone marrow transplantation. We
      investigated a murine model of GVHD across major and minor histocompatibility
      barriers. BALB/c recipients were lethally irradiated and transplanted with 10(7)
      bone marrow and 5 x 10(6) spleen cells from C57BL/6 donors. There were two
      separate phases of clinical disease. The first phase was most severe on day 7
      after transplant. Weight and condition improved until day 12 and then a second
      phase of clinical GVHD commenced, which persisted until euthanasia. IL-2 mRNA
      expression, as a measure of T cell activation, was determined by quantitative
      PCR. The two phases of clinical GVHD were preceded by two separate peaks of IL-2
      mRNA in the spleen. Host MHC class II(+) cells became undetectable by flow
      cytometry 7 days after transplantation, whereas donor MHC class II(+) cells
      increased during the first 9 days after transplantation. Removal of donor MHC
      class II(+) cells from the graft had no effect on the first phase. Possible roles
      for host and donor antigen-presenting cells (APC) in the two phases of the
      disease are discussed.

PMID- 11850711
TI  - Economic evaluation of filgrastim, sargramostim, and sequential sargramostim and
      filgrastim after myelosuppressive chemotherapy.
AB  - Filgrastim alone and sequential sargramostim and filgrastim have been shown to be
      more effective than sargramostim alone in the mobilization of CD34(+) cells after
      myelosuppressive chemotherapy (MC). We sought to compare costs and resource use
      associated with these regimens. Data were collected prospectively alongside a
      multicenter, randomized trial of filgrastim, sargramostim, and sequential
      sargramostim and filgrastim. Direct medical costs were calculated for inpatient
      and outpatient visits and procedures, including administration of growth factors
      and MC. We followed 156 patients for 30 days or until initiation of high-dose
      chemotherapy. The main outcome measures were resource use and costs of inpatient
      and outpatient visits, platelet and red blood cell transfusions, antibiotic use,
      and apheresis procedures. Hospital admissions, red blood cell transfusions, and
      use of i.v. antibiotics were significantly more common in the sargramostim group
      than in the other treatment arms. In univariate and multivariable analyses, total
      costs were higher for patients receiving sargramostim alone than for patients in
      the other groups. Mean costs in multivariable analysis for the filgrastim and
      sequential sargramostim and filgrastim arms were not significantly different.
      Filgrastim alone and sequential sargramostim and filgrastim are less costly than
      sargramostim alone after MC, as well as therapeutically more beneficial.

PMID- 11850712
TI  - Flow cytometric measurement of apoptosis and necrosis in cryopreserved PBPC
      concentrates from patients with malignant diseases.
AB  - The number of viable precursor cells actually reinfused into patients after high
      dose chemotherapy is one of the most clinically important variables determining
      graft success or failure. A modified, previously described flow cytometric method
      based on annexin V staining was therefore applied to assess the degree of
      apoptosis and necrosis in cryopreserved PBPC concentrates from patients with
      malignant diseases. Twenty-two samples of unmanipulated cryopreserved PBPC
      concentrates were analyzed by flow cytometry. The samples were triple-stained
      with anti-CD34 PE, annexin V-FITC and actinomycin D, which enabled the separation
      of viable, early apoptotic and late apoptotic/necrotic CD34(+) precursor cells.
      Apotosis and necrosis were also measured in the total cell population of the
      concentrates. Eighty-one percent (range 49-97) of the CD34(+) cells were viable,
      while 7% (range 1-15) were early apoptotic and 12% (range 2-36) were late
      apoptotic/necrotic after freeze/thaw. There was no difference in apoptosis and
      necrosis in CD34(+) cells harvested from mildly pretreated patients with multiple
      myeloma and heavily pre-treated patients with non-Hodgkin's lymphoma. Apoptosis
      and necrosis were higher in the total mature cell population of the concentrates.
      Thirty-two percent (range 7-69) of the cells were apoptotic and 33% (range 12-60)
      were necrotic. We conclude that flow cytometric analysis of annexinV/actinomycin
      D binding in PBPC concentrates is a simple technique that can give additional
      information of the viability status of the cells post thaw. The present study
      confirms the relative robustness of human CD34(+) precursor cells concerning the
      freeze/thaw procedure, which are carried out in daily clinical practice.

PMID- 11850713
TI  - Potential role of hematopoietic stem cell transplantation in children with
      secondary acute lymphocytic leukemia.
AB  - Secondary acute lymphocytic leukemias (ALL) are uncommon events in the pediatric
      patient population. There are few detailed reports on the laboratory
      characteristics and clinical course of patients with secondary lymphocytic
      leukemia. Historically, these patients have had a poor outcome. We report two
      patients treated at one institution who developed treatment-related secondary
      ALL. Both patients underwent hematopoietic stem cell transplantation, one with a
      compatible unrelated donor cord blood unit and one with an HLA-matched sibling
      donor bone marrow. One of the two patients survives disease-free 3 years after
      transplantation.

PMID- 11850717
TI  - Intratumoral gene therapy of malignant brain tumor in a rat model with
      angiostatin delivered by adeno-associated viral (AAV) vector.
AB  - We have utilized a recombinant adeno-associated viral (AAV) vector carrying the
      angiostatin gene as an anti-angiogenesis strategy to treat the malignant brain
      tumor in a C6 glioma/Wistar rat model. Angiostatin, as a potent angiogenesis
      inhibitor, shows high promises as an anti-cancer drug through the inhibition of
      tumor neovessel formation. However, sustained in vivo protein delivery is
      required to achieve the therapeutic effects. The AAV vector has been proven to be
      able to deliver sustained and high-level gene expression in vivo, and therefore,
      is well suited to such a purpose. In this study, we implanted 5 x 10(5) C6 glioma
      cells into the rat brain 7 days before gene therapy. Intratumoral injection of a
      high-titer AAV-angiostatin vector has rendered efficacious tumor suppression and
      resulted in long-term survival in 40% of the treated rats, whereas the control
      AAV-GFP vector did not have any therapeutic benefits. In addition, we have
      investigated the combined gene therapy of an adenoviral vector carrying the
      suicidal thymidine kinase gene along with the AAV-angiostatin vector. The
      combined therapy offered the best tumor-suppressive effects and increased long
      term survival to 55% in the treated rats. Our study has demonstrated the
      potential of using AAV as a safe and effective vector for anti-angiogenic gene
      therapy of brain tumors.

PMID- 11850718
TI  - Treatment of experimental equine osteoarthritis by in vivo delivery of the equine
      interleukin-1 receptor antagonist gene.
AB  - Osteoarthritis in horses and in humans is a significant social and economic
      problem and continued research and improvements in therapy are needed. Because
      horses have naturally occurring osteoarthritis, which is similar to that of
      humans, the horse was chosen as a species with which to investigate gene transfer
      as a potential therapeutic modality for the clinical treatment of osteoarthritis.
      Using an established model of equine osteoarthritis that mimics clinical
      osteoarthritis, the therapeutic effects resulting from intra-articular
      overexpression of the equine interleukin-1 receptor antagonist gene through
      adenoviral-mediated gene transfer were investigated. In vivo delivery of the
      equine IL-IRa gene led to elevated intra-articular expression of interleukin-1
      receptor antagonist for approximately 28 days, resulting in significant
      improvement in clinical parameters of pain and disease activity, preservation of
      articular cartilage, and beneficial effects on the histologic parameters of
      synovial membrane and articular cartilage. Based on these findings, gene transfer
      of interleukin-1 receptor antagonist is an attractive treatment modality for the
      equine patient and also offers future promise for human patients with
      osteoarthritis.

PMID- 11850714
TI  - Aggressive hepatocellular carcinoma complicating pregnancy after autologous bone
      marrow transplantation for non-Hodgkin's lymphoma.
AB  - In the Asia-Pacific region, autologous and allogeneic bone marrow transplantation
      (BMT) in patients infected with the hepatitis B virus (HBV) may be complicated by
      fatal hepatic failure due to viral reactivation. Survivors may suffer from
      accelerated hepatitis and cirrhosis. We report the first case of hepatocellular
      carcinoma (HCC) after autologous BMT for mediastinal B cell lymphoma. The tumor
      developed rampantly during a planned pregnancy 5 years after BMT. Less than 40
      cases of HCC complicating pregnancy have been reported, and outcome is invariably
      poor. Immunosuppression and HBV reactivation after autologous BMT, as well as
      immune tolerance and hormonal changes associated with pregnancy may contribute to
      the rapid tumor growth. Biochemical and radiological surveillance for HCC should
      be strengthened in HBV carriers after BMT, especially in patients with the
      histology of chronic liver disease, or biochemical/ virological evidence of
      increased HBV activity.

PMID- 11850719
TI  - Inhibition of atherosclerosis in apolipoprotein-E-deficient mice following muscle
      transduction with adeno-associated virus vectors encoding human apolipoprotein-E.
AB  - Apolipoprotein E (apoE) is a multifunctional plasma glycoprotein involved in
      lipoprotein metabolism and a range of cell signalling phenomena. ApoE-deficient
      (apoE(-/-)) mice exhibit severe hypercholesterolaemia and are an excellent model
      of human atherosclerosis. ApoE somatic gene transfer and bone marrow
      transplantation in apoE(-/-) mice results in reversal of hypercholesterolaemia,
      inhibition of atherogenesis and regression of atherosclerotic plaque density.
      Replication defective adeno-associated virus vectors (rAAVs) are an attractive
      system currently in clinical trial for muscle-based heterologous gene therapy to
      express secreted recombinant plasma proteins. Here we have applied rAAV
      transduction of skeletal muscle to express wild-type (epsilon3) and a defective
      receptor-binding mutant (epsilon2) human apoE transgene in apoE(-/-) mice. In
      treated animals, apoE mRNA was present in transduced muscles and, although plasma
      levels of recombinant apoE fell below the detection levels of our ELISA (ie <10
      ng/ml), circulating antibodies to human apoE and rAAV were induced. Up to 3
      months after a single administration of rAAV/apoE3, a significant reduction in
      atherosclerotic plaque density in aortas of treated animals was observed
      (approximately 30%), indicating that low-level rAAV-mediated apoE3 expression
      from skeletal muscle can retard atherosclerotic progression in this well-defined
      genetic model.

PMID- 11850720
TI  - hTERT promoter induces tumor-specific Bax gene expression and cell killing in
      syngenic mouse tumor model and prevents systemic toxicity.
AB  - We recently showed that the human telomerase reverse transcriptase (hTERT)
      promoter induces tumor-specific Bax gene expression and selectively kills various
      human cancer cells both in vitro and in xenograft tumors. However, it remains
      unclear whether the hTERT promoter can be used to induce transgene expression in
      syngenic tumors in mice and whether Bax gene expression driven by the hTERT
      promoter will cause long-term, stem cell-related toxicity. To address these
      questions, we tested hTERT promoter-driven, adenovirus-mediated Bax transgene
      expression in an established syngenic mouse tumor model and its effects on tumor
      and normal murine tissues. The hTERT promoter was highly active in several murine
      tumor cell lines and a transformed cell line, but not in non-transformed and
      normal murine cell lines. The hTERT promoter induced tumor-specific Bax gene
      expression in mouse UV-2237m fibrosarcoma cells both in vitro and in vivo and
      suppressed syngenic tumor growth in immune-competent mice with no obvious acute
      or long-term toxic effects. Moreover, hTERT promoter-driven transgene expression
      in human CD34(+) bone marrow progenitor cells had effects similar to those
      observed in other normal human cells, suggesting that the hTERT promoter is much
      less active in CD34(+) cells than in tumor cells. Together, our data demonstrate
      that the hTERT promoter may allow the use of proapoptotic genes for cancer
      treatment without noticeable effects on progenitor cells.

PMID- 11850721
TI  - Suppression of cutaneous inflammation by intradermal gene delivery.
AB  - Biological effects of in vivo transfection of a potential anti-inflammatory gene,
      designated Sm16, cloned from the human parasite Schistosoma mansoni were analyzed
      in these studies. A single intradermal injection of a full-length cDNA of Sm16
      resulted in the expression of Sm16 in the epidermis, dermis, skin migratory cells
      and skin-draining lymph nodes of mice for up to 7 days. Subsequently the anti
      inflammatory effect of this gene expression was evaluated by inducing an
      inflammatory response in the skin of mice. These studies showed that Sm16 gene
      delivery resulted in a significant suppression of cutaneous inflammation as shown
      by a reduction in cutaneous edema, decrease in neutrophil infiltration,
      suppression of pro-inflammatory cytokine expression and down-regulation of ICAM-1
      expression in the skin inflammatory site. Cells collected from the skin-draining
      lymph nodes showed reduced proliferation to mitogen. Multiple intradermal
      injection of Sm16 cDNA failed to induce any antibody response in mice for up to 8
      weeks after initial injection. These findings suggest a potential for developing
      Sm16 gene delivery as a therapeutic agent for treating inflammatory skin
      disorders.

PMID- 11850722
TI  - Brain engraftment of autologous macrophages transduced with a lentiviral flap
      vector: an approach to complement brain dysfunctions.
AB  - Transplantation of ex vivo gene-corrected autologous cells represents an
      attractive therapeutic approach for brain diseases. Among the cells of the
      central nervous system, brain macrophages are promising candidates due to their
      role in tissue homeostasis and their implication in several neurological
      diseases. Up to now, gene transfer into macrophages has proven difficult by most
      currently available gene delivery methods. We describe herein, an efficient
      transduction of rat bone marrow-derived and brain macrophages with an HIV-1
      derived vector containing a central DNA flap and encoding the GFP reporter gene
      (TRIP-DeltaU3-GFP). In primary cultures of macrophages our results show that more
      than 90% of the cells were transduced by the TRIP vector and that GFP expression
      remained stable for 1 month without cytopathic effect. In vivo, transplants of
      transduced macrophages into the striatum of adult rats exhibited long-term
      expression of GFP up to 3 months. Transduced macrophages were observed around the
      brain injection site and exhibited the brain macrophage/microglia phenotype.
      There was no significant sign of astrogliosis around the graft. These results
      confirm the potential of lentiviral vectors for efficient and stable ex vivo
      transduction of macrophages. Moreover, transduced autologous macrophages appear
      as a valuable vehicle for long-term and localized gene expression into the brain.

PMID- 11850723
TI  - Bone marrow stem cell-based gene transfer in a mouse model for metachromatic
      leukodystrophy: effects on visceral and nervous system disease manifestations.
AB  - Arylsulfatase A (ASA) knockout mice represent an animal model for the lysosomal
      storage disease metachromatic leukodystrophy (MLD). Stem cell gene therapy with
      bone marrow overexpressing the human ASA cDNA from a retroviral vector resulted
      in the expression of high enzyme levels in various tissues. Treatment partially
      reduces sulfatide storage in livers exceeding 18 ng ASA/mg tissue, while complete
      reduction was observed in livers exceeding 50 ng ASA/mg tissue. This corresponds
      to about 80% and 200% of normal enzyme activity. Similar values seem to apply for
      kidney. A partial correction of the lipid metabolism was detectable in the brain
      where the galactoerebroside/sulfatide ratio, which is diminished in ASA-deficient
      mice, increased upon treatment. This partial correction was accompanied by
      amelioration of neuropathology; axonal cross-sectional areas, which are reduced
      in deficient mice, were significantly increased in the saphenic and sciatic nerve
      but not in the optic nerve. Behavioral tests suggest some improvement of
      neuromotor abilities. The gene transfer did not delay the degeneration occurring
      in the acoustic ganglion of ASA-deficient animals. The limited success of the
      therapy appears to be due to the requirement of unexpected high levels of ASA for
      correction of the metabolic defect.

PMID- 11850724
TI  - Effective gene therapy for medullary thyroid carcinoma using recombinant
      adenovirus inducing tumor-specific expression of interleukin-12.
AB  - No satisfactory treatment of metastatic medullary thyroid carcinoma (MTC) is
      available. Cell-specific gene therapy offers a new approach. We have constructed
      a recombinant replication-defective adenoviral vector expressing murine
      interleukin-12 (mIL-12), driven by a modified CALC-I promoter (TCP). This vector
      (AdTCPmIL-12) includes two separate cassettes encoding mIL-12 p35 or p40 subunit
      controlled by TCP inserted in the E1 region of adenovirus type 5. In vitro and in
      vivo reporter gene expression using TCP revealed its cell-specific activity.
      AdTCPmIL-12-infected rat MTC (rMTC) cells produced high amounts of functional mIL
      12 cells in vitro, while other cell lines infected with AdTCPmIL-12 did not.
      AdTCPmIL-12-transduced rMTC cells completely lost their tumorigenicity in
      syngenic WAG/Rij rats. Direct injection of 1 x 10(9) plaque forming units of
      AdTCPmIL-12 into subcutaneous rMTC tumors in WAG/Rij rats caused tumor regression
      in over 60% of animals within 20 days. Rats cured of tumors did not develop
      tumors after re-injection of naive rMTC cells, demonstrating lasting immunity.
      Treatment with AdTCPmIL-12 of one tumor resulted in regression of an established
      tumor at a distant site. Moreover, intratumoral or intravenous injection of
      AdTCPmIL-12 did not induce evident toxicity. These results indicate AdTCPmIL-12
      can contribute to effective and less toxic gene therapy of MTC.

PMID- 11850725
TI  - The use of a genetically engineered herpes simplex virus (R7020) with ionizing
      radiation for experimental hepatoma.
AB  - The herpes simplex virus (HSV) recombinant virus R7020 is an attenuated virus
      designed as a candidate for immunization against both HSV-1 and HSV-2 infections.
      It was extensively tested in an experimental animal system and in a healthy human
      adult population without significant untoward effects. We report on the use of
      R7020 with ionizing radiation as an oncolytic agent for hepatomas. Two hepatoma
      cell lines were studied, Hep3B and Huh7. R7020 replicated to higher titers in
      Hep3B cells than in Huh7 cells. Tissue culture studies correlated with hepatoma
      xenograft responses to R7020. R7020 was more effective in mediating Hep3B tumor
      xenograft regression compared with Huh7. Ionizing radiation combined with R7020
      also showed differential results in antitumor efficacy between the two cell lines
      in tumor xenografts. Ionizing radiation enhanced the replication of R7020 in
      Hep3B xenografts. Moreover, the combination of ionizing radiation and virus
      caused a greater regression of xenograft volume than either R7020 or radiation
      alone. Ionizing radiation had no effect on the replication of R7020 virus in Huh7
      xenografts. These results indicate that a regimen involving infection with an
      appropriate herpesvirus such as R7020 in combination with ionizing radiation can
      be highly effective in eradicating certain tumor xenografts.

PMID- 11850727
TI  - Proceedings of the 2nd International Conference on Management of Erectile
      Dysfunction: New Perspectives on Treatment. June 28-30, 2001. London, England,
      United Kingdom.

PMID- 11850726
TI  - Induction of cyclo-oxygenase-2 in non-small cell lung cancer cells by infection
      with DeltaE1, DeltaE3 recombinant adenovirus vectors.
AB  - Infection of epithelial-derived cells by adenovirus vectors has myriad effects on
      cellular behavior and function. Some are relevant to the desired effect of the
      encoded transgene and therapeutic goals of gene therapy approach. The current
      experiments describe the induction of COX-2 protein and PGE-2 production by non
      small cell lung cancer (NSCLC) cells following infection with a first generation
      (DeltaE1, DeltaE3) Ad vector. COX-2 overexpression by malignant cells has been
      shown to enhance cellular invasion, induce angiogenesis, regulate anti-apoptotic
      cellular defenses and augment immunologic resistance through production of PGE-2.
      Data show DeltaE1, DeltaE3, Ad5 vector infection induces dose-dependent increases
      in PGE-2 production by NSCLC cell lines. Data with UV/psoralen inactivated
      vectors and control vectors show this effect is dependent on Ad vector gene
      expression, but independent of the transgene expressed. Selective blockade of ERK
      with PD98029 abrogated induction of PGE-2 by Ad vectors. Consistent with these
      data, detectable increases in COX-2 protein were seen at 48 h after infection by
      Western blot that were paralleled by increases in the phosphorylation of ERK-1/2.
      UV/psoralen-inactivated vector did not induce COX-2 protein or ERK
      phosphorylation at 48 h. Further, an inhibitor of NF-kappa B (NFkappaB)
      translocation to the nucleus, SN50, had no effect on PGE-2 levels. In contrast,
      Ad vector infection did induce NFkappaB activity measured by NFkappaB-luciferase
      reporter plasmid, transfected into a NSCLC cell line. Collectively the data
      indicate DeltaE1, DeltaE3, Ad5 vector infection leads to ERK phosphorylation with
      parallel increases in COX-2 protein and PGE-2 production. These effects appear
      unrelated to NFkappaB and are dependent on gene expression by the vector. This
      information may need to be considered when defining targets for cancer gene
      therapy and/or the choice of viral vector.

PMID- 11850728
TI  - Molecular mechanisms for the regulation of penile smooth muscle contractility.
AB  - Relaxation of penile smooth muscle (arterial and trabecular) initiates and
      maintains penile erection. Relaxation of smooth muscle is viewed as a 'resetting'
      of contractile machinery by resumption of a precontractile state accomplished by
      lowering cytosolic Ca(+2) and/or by a decrease in sensitivity of the contractile
      machinery to Ca(+2). There are various mechanisms whereby cytosolic Ca(+2) can be
      reduced and relaxation achieved, but in general, all pathways depend on the
      accumulation of the nucleotides cyclic adenosine monophosphate (cAMP) and cyclic
      guanosine monophosphate (cGMP) or activation of K channels with
      hyperpolarization. Another mechanism, activation of Na(+)/K(+) adenosine
      triphosphatase (ATPase) by nitric oxide, has been shown to be involved in
      relaxation of trabecular smooth muscle. Since Na(+)/K(+) ATPase is electrogenic,
      its stimulation would cause hyperpolarization. Hyperpolarization will prevent the
      opening of voltage-dependent calcium channels. Guanylate cyclase, which catalyzes
      the conversion of guanosine triphosphate to cGMP, is activated by nitric oxide.
      cGMP activates protein kinase G, which through multiple phosphorylations
      facilitates calcium sequestration and reduces the entry of calcium into the cell.
      Other muscle relaxants act by way of a cAMP-dependent mechanism such as
      prostaglandin E, vasoactive intestinal polypeptide, and catecholamines (via beta
      receptors). These substances react with membrane receptors coupled to a GS-type
      protein that stimulates adenylate cyclase, which catalyzes the accumulation of
      cAMP. DOI: 10.1038/sj/ijir/3900790

PMID- 11850729
TI  - Is there a common pathophysiology of erectile dysfunction and how does this
      relate to new pharmacotherapies?
AB  - Many basic and clinical studies show erectile dysfunction (ED) to be caused by a
      wide variety of factors. Although these factors can be divided into psychological
      and organic origins and these too can further be subdivided, many patients will
      show complex patterns of causes for ED ('mixed ED'). Many of these factors will
      have a direct or indirect impact on the efficacy of centrally and peripherally
      acting drugs, thus necessitating a variety of drugs with different modes of
      action and different modes of application to ensure appropriate therapy for many
      patients. However, some factors will render all imaginable forms of
      pharmacological options totally inefficient, thus necessitating forms of
      treatment other than pharmacotherapy.

PMID- 11850731
TI  - Prevalence of erectile dysfunction: need for treatment?
AB  - Research examining the occurrence of sexual problems in nonclinical populations
      tends to be restricted to highly select populations. Recently, several population
      based surveys surfaced in the international literature, triggered by the advent
      of effective pharmacological treatment for erectile dysfunction (ED). ED is a
      common disorder, especially among elderly men. The annual incidence in men 40-69
      y of age is 26 per 1000 men. Although most of the difficulties are mild and do
      not totally prevent intercourse, about 26% of men experience moderate to complete
      ED. The impact of this category of ED on sexual activity among men is marked. The
      incidence of ED increases with age and the presence of concomitant conditions,
      such as diabetes mellitus, heart disease, hypertension, depression, pelvic
      surgery, negative mood, lack of self-esteem, problems with relationships, or just
      inadequate sexual experience. Vascular disease is thought to be the most common
      cause of organic ED, and it may be an early symptom of cardiac morbidity and
      mortality. Although one may expect that any man with ED who is motivated to
      continue sexual activity may seek current highly effective symptomatic medical
      treatment, only a few men are actually seeking help, and not every man seeking
      help appears to be a candidate for (symptomatic) medical treatment. The frequent
      association of sexual and medical problems, especially in the aged, and the high
      dropout rates for symptomatic ED treatment make counseling, adjustment of
      lifestyle, and modification of risk factors, such as medication, overweight,
      smoking, alcohol consumption, and lack of exercise, the primary steps in a
      holistic approach toward the treatment of ED. It is especially important to
      educate these men to remain physically and sexually as active as possible for as
      long as possible. The phrase 'use it or lose it' is particularly appropriate for
      the genitalia.

PMID- 11850730
TI  - Smooth muscle pathology and erectile dysfunction.
AB  - Penile erection is a vascular phenomenon that results from smooth muscle
      relaxation, arterial dilation and venous restriction. The atherosclerosis of the
      penis that occurs with aging causes a decrease in penile oxygen tension. A
      reduction of smooth muscle cells has been demonstrated in relation with this
      change in oxygen tension. Changes in the ratio of penile collagen have also been
      observed and could explain the decrease in penile elasticity and compliance.
      Chronic ischemia is, therefore, associated with fibrosis but also with nitric
      oxide (NO)-cyclic guanosine monophosphate. The sensitivity of the alpha
      adrenoceptors on the smooth muscle cells increases with aging. All those
      modifications can explain the prevalence of erectile dysfunction with aging. Low
      oxygen tension in prostanoid production may also play a role in the mechanism of
      ischemia-induced cavernosal fibrosis; however, intracavernous injections of
      prostaglandin E(1) do not seem to modify the intracavernous structures by
      reducing muscular atrophy. The effects of androgen on libido and sexual behavior
      are well established, but their role in the human erectile mechanism remains
      unclear. Several studies performed on animals have demonstrated impacts directly
      on both the physiological function and the trabecular structure of the corpora
      cavernosa in rats, dogs and rabbits. However, in humans, no study seems to
      demonstrate a role of testosterone on muscular atrophy or penile neurologic
      control. Testosterone treatment alters the human behavior but not penile
      physiologic processes. Further studies are necessary to explain the real role of
      testosterone not only on the peripheral mechanism of erection but also on the
      central control.

PMID- 11850732
TI  - Erectile dysfunction in the 21st century: whom we can treat, whom we cannot treat
      and patient education.
AB  - Erectile dysfunction affects 31-52% of American men. Although considerable
      advances have been made in the diagnosis and treatment of erectile dysfunction in
      the past decade, more than 80% of men with erectile dysfunction are not treated
      because they do not seek medical attention or their physicians do not initiate a
      dialogue about sexual problems during their visits. This despite patients'
      desires to confront sexual problems and receive treatment. Most subgroups of men
      can now be effectively treated for sexual dysfunction. Although men with severe
      cardiac disease may require stabilization of their cardiac condition before
      treatment, most can successfully return to an active sex life. Some men, however,
      do not respond to the use of oral agents. These men can be treated with second-
      and third-line treatment modalities or with the newer concept of combined
      modality treatment. Despite excellent treatment alternatives, many men have low
      libido or hypoactive sexual desire disorder. In the ultimate resolution of a
      patient's sexual dysfunction, physicians must open a free and sympathetic
      dialogue and offer a full spectrum of treatment modalities tailored to the
      individual patient and partner. If initial treatment modalities fail, more
      invasive alternatives or combination therapy should be offered to cure the
      patient's erectile dysfunction.

PMID- 11850733
TI  - Clinical trial designs: is it possible to have a unified approach and common end
      points?
AB  - The accelerating development during the last 5 y of new compounds for the medical
      treatment of erectile dysfunction (ED) demands standardized high-quality
      protocols for evaluation of the therapeutic effect of these treatments. Outcome
      analyses have to rely on prospective, placebo-controlled trials within predefined
      populations, where the results are based on good biostatistics, self-administered
      questionnaires that include partner assessments, quality-of-life measures, and
      treatment satisfaction. Currently, we have access to different drug application
      procedures for clinical use in the treatment of ED, and soon we will have new
      competitive analogues for optional oral treatment. From a wider perspective, we
      will naturally see second- and third-generation compounds and drugs related to
      different effector mechanisms. In many subpopulations, ED has a close relation to
      specific comorbidities, such as cardiovascular diseases and diabetes. Regarding
      these aspects, the baseline for all clinical trials should be unified and
      structured not only to evaluate the clinical outcome assessment (subjective and
      objective) and adverse events as end points, but also to relate the defined
      therapeutic response to good current clinical practice.

PMID- 11850734
TI  - Rationale for combination therapy of intraurethral prostaglandin E(1) and
      sildenafil in the salvage of erectile dysfunction patients desiring noninvasive
      therapy.
AB  - Corpus cavernosum smooth muscle relaxation and hence penile erection are
      regulated in part by increases in smooth muscle synthesis of the second
      messengers cyclic adenosine monophosphate (cAMP) and cyclic guanosine
      monophosphate (cGMP). The object of this study was to determine 30-month follow
      up results in motivated patients desiring noninvasive medical therapy using
      sildenafil citrate (Viagra) in combination with intraurethral prostaglandin E(1)
      (PGE(1)) (Medicated Urethral System for Erection [MUSE]). Twenty-eight patients
      (mean +/- s.d. age, 59 +/-7.3 y; 17 who had undergone radical prostatectomy and
      11 who had a diagnosis of organic erectile dysfunction) were included in this
      study. Detailed history taking and physical examinations were performed and
      vascular risk factors noted. In these patients, treatment with either 100 mg of
      sildenafil citrate and/or 1000 microg of MUSE had failed. None of these patients
      desired intracavernosal injection. Duplex Doppler ultrasonography after redosing
      was carried out on all patients. Dynamic infusion corpus
      cavernosography/cavernosometry was obtained in 17 of 28 patients, and combination
      therapy was initiated using 100 mg of sildenafil citrate orally 60 min before
      intercourse and 500 microg of MUSE intraurethrally immediately before
      intercourse. Independently, either 100 mg of sildenafil citrate or 1000 microg of
      MUSE was not efficacious in inducing an erection sufficient for vaginal
      penetration in any of the 28 patients. After initiating a combination therapy, at
      30 months, all 28 patients were reporting erections sufficient for vaginal
      penetration, with 3.6 intercourse episodes per month. None of the patients
      crossed over to intracavernosal therapy or penile prosthesis. During therapy,
      eight of 28 patients reduced the dose of sildenafil citrate to 50 mg. Combination
      therapy with MUSE and sildenafil may be more efficacious in the salvage of
      patients who desire noninvasive therapy but in whom single-treatment modalities
      fail. Although both cAMP- and cGMP-mediated vasodilation can lead to penile
      erection, combining therapies that incorporate both pathways may succeed when
      single therapies fail.

PMID- 11850735
TI  - Sildenafil citrate: lessons learned from 3 years of clinical experience.
AB  - In the 3 y since its initial approval, sildenafil has become the most widely used
      treatment for erectile dysfunction (ED) and has been prescribed to more than 13
      million patients worldwide. Significant improvements in erectile function have
      been demonstrated in double-blind, placebo-controlled studies in diverse patient
      populations. A significant treatment effect has been shown with sildenafil in men
      with ED and a history of diabetes, cardiovascular disease, minor depression,
      spinal cord injury and multiple sclerosis. In addition, promising results have
      been shown in patients with treated prostate cancer, end-stage renal disease,
      Parkinson's disease and spina bifida and in multiple-organ transplant recipients.
      Postmarketing data of the use of sildenafil in clinical practice confirm the
      efficacy and safety found in clinical trials and high satisfaction with
      treatment. Public awareness of the common occurrence of ED and the high
      likelihood of a potentially favorable response to an oral treatment increased
      dramatically with the introduction of sildenafil. Physicians, however, are still
      not comfortable with ED management, which negatively affects pharmacotherapy
      response rates and patients' compliance to treatment. Continuing medical
      education seems mandatory to overcome existing problems in ED management.

PMID- 11850736
TI  - Apomorphine SL (Uprima): preclinical and clinical experiences learned from the
      first central nervous system-acting ED drug.
AB  - An exclusive central site of action for the proerectile effect of apomorphine,
      including not only the brain but also the spinal cord, is supported by extensive
      experimental data. Assuming that the mechanisms of action of apomorphine are
      similar in humans and animal models, its use for the treatment of erectile
      dysfunction (ED) validates the emerging idea that erectile response could be
      enhanced by acting directly within the central nervous system (CNS). It also
      emphasized the key role of the dopaminergic system in the control of erection. As
      exemplified with the clinical development of apomorphine, targeting the CNS does
      not rule out the occurrence of undesirable side effects. Because the rare event
      of syncope induced by apomorphine is not well understood, further research should
      be conducted to explore its possible mechanisms. In clinical practice, however,
      approved doses of apomorphine SL are well tolerated. It is noteworthy that no
      modification of sexual desire was observed with apomorphine. Indeed, drugs acting
      within the CNS may more likely interact with sexual desire than peripherally
      acting drugs, and care should be taken to assess this point in the future.
      Although our knowledge of the control of penile erection by the CNS is
      restricted, there are many potential sites for CNS-acting ED drugs. New centrally
      acting therapy for ED should concentrate on receptor targets more specific to
      erectile command. Clinical efficacy of new centrally-acting compounds will assess
      the well-founded purpose of this rationalization.

PMID- 11850737
TI  - IC351 (tadalafil, Cialis): update on clinical experience.
AB  - IC351 (tadalafil, trade name Cialis) is a new representative compound of the
      second generation of selective phosphodiesterase 5 (PDE-5) inhibitors. The
      selectivity ratio vs PDE-5 is more than 10 000 for PDE-1 through PDE-4 and PDE-7
      through PDE-10 and 780 for PDE-6. In the European daily-dosing trial, the
      efficacy rates were up to 93% for successful intercourses with completion in the
      50-mg dose in patients with mild to moderate erectile dysfunction (ED). In two
      different dose-ranging studies with 2-25 mg taken as needed, efficacy rates of up
      to 88% improvement in erections and up to 73% successful intercourses with
      completion were achieved. In a placebo-controlled, fixed-dose (10- and 20-mg)
      trial in diabetic patients, improved erections of 56% and 64% were reported
      compared with 25% after placebo. Drug-related adverse effects, with headache in
      up to 23% of patients (placebo, up to 17%), dyspepsia in up to 11% (placebo, up
      to 7%), back pain in up to 4.7% (placebo, 0%), and myalgia in up to 4.1%
      (placebo, up to 2.4%), were mostly mild to moderate. Neither drug-related serious
      cardiovascular adverse events nor color vision disturbances were encountered. The
      long half-life (>17 h), with a comfortably long window of opportunity, releases
      couples from the need to plan sexual activities and therefore provides the
      highest amount of spontaneity for sexual activities.

PMID- 11850738
TI  - Vardenafil: update on clinical experience.
AB  - Vardenafil, a potent and selective phosphodiesterase 5 inhibitor, has entered
      phase 3 clinical trials. Pharmacodynamic studies showed that the maximum plasma
      concentration after oral administration of 20-40 mg of vardenafil occurred in 0.7
      0.9 h, the half-life was 4-5 h, and negligible amounts remained in the
      circulation after 24 h. The efficacy of vardenafil compared with placebo was
      shown in RigiScan studies, a phase 2 study involving 601 men with mild-to-severe
      erectile dysfunction for at least 6 months, and a phase 3 study involving 452
      diabetic men. Adverse effects were not severe and tended to decrease with time.

PMID- 11850739
TI  - Current status of local penile therapy.
AB  - Guidelines for management of patients with erectile dysfunction indicate that
      intraurethral and intracavernosal injection therapies represent the second-line
      treatment available. Efficacy of intracavernosal injections seems superior to
      that of the intraurethral delivery of drugs, and this may explain the current
      larger diffusion of the former modality. Safety of these two therapeutic options
      is well established; however, the attrition rate with these approaches is
      significant and most patients eventually drop out of treatment. Newer agents with
      better efficacy-safety profiles and using user-friendly devices for drug
      administration may potentially increase the long-term satisfaction rate achieved
      with these therapies. Topical therapy has the potential to become a first-line
      treatment for erectile dysfunction because it acts locally and is easy to use. At
      this time, however, the crossing of the barrier caused by the penile skin and
      tunica albuginea has limited the efficacy of the drugs used.

PMID- 11850740
TI  - New directions for erectile dysfunction therapies.
AB  - Research in the field of erectile function and dysfunction has continued to
      expand rapidly. Based on the information available, some directions for future
      erectile dysfunction therapies can be identified. The first direction is
      improvement of current therapeutic principles. A second generation of orally
      active phosphodiesterase (PDE) inhibitors is being introduced, and further
      developments within this field can be expected. The recent introduction of
      apomorphine has opened the way for new dopamine receptor agonists. The second
      direction is combinations of existing therapeutic principles. Combinations of
      apomorphine and sildenafil and apomorphine and alpha(1)-adrenoceptor (AR)
      antagonists, for example, seem attractive and may have a therapeutic potential in
      patients not responding satisfactorily to single-drug treatment. Nitrosylated
      alpha(1)-AR antagonists, combining nitric oxide donation and alpha(1)- or
      alpha(2)-AR antagonism, are currently being evaluated. The third direction is new
      targets within the central nervous system. Melanocortin receptor agonists have
      shown promise not only in animal models, but also in preliminary studies in
      humans. Other possible targets, such as growth hormone-releasing peptide
      receptors, are being explored. The fourth direction is new peripheral targets.
      Rho-kinase antagonism and non-nitric oxide-mediated stimulation of soluble
      guanylyl cyclase have been suggested as possible new principles for drug
      development. The fourth direction is gene therapy. Progress has been made in
      intracavernosal somatic gene therapy and will probably continue. Still, problems
      remain, and advantages over conventional pharmacological therapies have to be
      demonstrated. The final direction is prevention strategies. Strategies to prevent
      cavernosal degeneration and/or to restore cavernosal function will be one of the
      most exciting challenges for future research.

PMID- 11850741
TI  - Male andropause: myth, reality, and treatment.
AB  - A progressive decrease in androgen production is common in aging men. The
      physiological causes for this phenomenon seem to be multifactorial. The magnitude
      of the decline in testosterone with age and the prevalence of older men with low
      testosterone levels have not been well established. The extent to which an age
      dependent decline in androgen levels leads to health problems that might affect
      or alter the quality of life remains under debate. In men older than middle age,
      total testosterone levels may be misleading because of an increase in sex hormone
      binding globulin levels. The mechanism of the age-associated decrease of the
      endocrine testicular function is also essentially due to primary testicular
      failure, but important changes occur at the hypothalamopituitary level. The most
      prominent endocrinological alterations with aging are related to the sex
      steroids, but others, such as growth hormone, melatonin cortisol, and thyroxine,
      are also affected. The clinical picture of andropause syndrome is characterized
      by diminished sexual desire and erectile capacity, decrease in intellectual
      activity, fatigue, depression, decrease in lean body mass, skin alterations,
      decrease in body hair, decrease in bone mineral density that results in
      osteoporosis, and increase in visceral fat and obesity. Current medical
      treatments for androgen supplementation include oral tablets, intramuscular
      injections, and scrotal and nonscrotal patches. Unfortunately, none of these
      preparations mimic the circadian rhythm, even if some of them may approximate the
      circadian rhythm by dose adjustments. Moreover, the androgen supplementation
      could have adverse effects on different organs, namely, the liver, lipid profile,
      cardiovascular disease, prostate, sleep disorders, and emotional behavior.
      Clinical response is a better guide to dose requirements, regardless of serum
      testosterone levels. This important field must be actively investigated by the
      medical, behavioral, and social sciences.

PMID- 11850742
TI  - When an erection alone is not enough: biopsychosocial obstacles to lovemaking.
AB  - Giving men firm erections is relatively straightforward these days; getting them
      to make use of it regularly in lovemaking is more complicated. Discontinuation
      rates for any of the available medical treatments for erectile dysfunction,
      including sildenafil, have been found to range from 50% to 60%. Thus, there is a
      disproportionately high number of individuals who fail to continue using medical
      interventions compared to those for whom treatment is efficacious. If not
      efficacy, then what factors contribute to this puzzling dropout phenomenon? This
      article discusses the psychological resistances of men, women, and couples that
      contribute to their stopping treatment for erectile dysfunction. Some of the
      factors that may be responsible include: (1) the length of time the couple was
      asexual before seeking treatment; (2) the man's approach to resuming a sexual
      life with his partner; (3) the man's expectations of how sildenafil will change
      his life; (4) the partner's physical and emotional readiness to resume
      lovemaking; (5) the meaning for each partner of using a medical intervention to
      restore lovemaking; (6) the quality of the nonsexual relationship; and (7)
      unconventional sexual arousal patterns in the man. To be effective, clinicians
      must go beyond the simple restoration of erectile function to help patients
      become active lovemakers again.

PMID- 11850743
TI  - The role of the partner in erectile dysfunction and its treatment.
AB  - Advances in pharmacological, mechanical, and surgical treatment for erectile
      dysfunction (ED) now allow erectile function to be re-established in most men who
      experience this problem. However, re-establishing erectile function and re
      establishing a satisfying sexual interaction with a partner are totally different
      objectives, and when the latter is not met, the man may re-present with treatment
      failure or withdraw from treatment altogether. All nontalking therapies focus on
      the penis as the dysfunctional element, and all too often clinicians fail to
      appreciate that ED can result from problems in the patient's partner and/or
      difficulties in their relationship. This article examines the role of the partner
      in the etiology, assessment, and treatment of ED.

PMID- 11850744
TI  - Chronic central infusion of cocaine- and amphetamine-regulated transcript (CART
      55-102): effects on body weight homeostasis in lean and high-fat-fed obese rats.
AB  - BACKGROUND: Cocaine- and amphetamine-regulated transcript (CART) is expressed
      within hypothalamic nuclei implicated in the regulation of feeding behaviour. It
      is up-regulated by leptin, and CART-derived peptides acutely inhibit food intake.
      OBJECTIVE: The present study was designed to assess the long-term effects of
      central CART administration on food intake, body weight, plasma levels of
      glucose, insulin, leptin, free fatty acids and triglycerides, and on fuel
      utilisation in normal and high-fat-fed obese rats. DESIGN: Normal and high-fat
      fed obese rats were cannulated intracerebroventricularly (i.c.v.) and infused for
      6 days with CART (55-102) or its vehicle. At day 4, animals were placed in an
      indirect calorimeter for a 24 h period during which the respiratory quotient and
      the energy expenditure were determined hourly. RESULTS: In both normal and obese
      animals, the chronic i.c.v. infusion of CART (55-102) had marked, sustained
      inhibitory effects on food intake and body weight gain that were accompanied by
      decreases in plasma insulin and leptin levels. Using indirect calorimetry, it was
      observed that CART infusion promoted an increase in lipid oxidation in normal and
      in obese animals, although this increase reached statistical significance only in
      the obese group. The hypothalamic CART mRNA expression was found to be higher in
      obese rats (displaying hyperleptinaemia) than in normal animals. CONCLUSION: The
      data together show that chronic i.c.v. CART infusion is effective in inhibiting
      food intake, favouring lipid oxidation and limiting fat storage, both in normal
      and high-fat-diet-induced obese rats. The CART pathway thus seems to be an
      important determinant of body weight homeostasis in normal animals as well as in
      a model of nutritionally induced obesity.

PMID- 11850745
TI  - Habitual fat intake and basal fat oxidation in obese and non-obese Caucasians.
AB  - OBJECTIVE: To examine the relationship between habitual fat intake and basal fat
      oxidation in obese and non-obese Caucasian men and women. METHODS: Habitual fat
      intake was assessed by 7-day weighed dietary records and resting fat oxidation
      was determined after an overnight fast in 132 weight stable non-diabetic subjects
      (38 males, 94 females). All subjects were characterized for weight, height, waist
      to-hip ratio, physical activity, plasma glucose and insulin response to an oral
      glucose load, plasma catecholamine and leptin levels. Under-reporters, defined
      according to plausibility of the relationship between energy expenditure and
      energy intake, were excluded from the analyses. RESULTS: The mean age was 53.1+/
      10.6 y (19-72 y) and mean body mass index (BMI) was 30.7+/-5.8 kg/m(2) (19.4-45.8
      kg/m(2)). Sixty-eight subjects were obese (BMI>30 kg/m(2)). Univariate regression
      analysis revealed a significant, albeit modest, relationship between absolute fat
      intake and BMI (r(2)=0.06; P<or=0.05) but not between fat intake and fat mass
      (r(2)=0.026; P=0.08). However, multiple regression analysis revealed significant
      effects of body fat mass (FM) and sex on basal fat oxidation (bFO) explaining 33%
      of the variation of bFO (P<or=0.0001; radical s.e.=18.0 g/24 h). In univariate
      regression analysis, habitual fat intake was significantly related to adjusted
      fat oxidation, explaining 12% of the variation (P<or=0.0001; radical s.e.=11.7
      g/24 h). CONCLUSION: Habitual fat intake has a significant, albeit modest, effect
      on basal fat oxidation, even when adjusted for sex and body FM. The rather modest
      effect of habitual fat intake on fat oxidation may in part explain the increased
      propensity to gain FM on a high-fat diet.

PMID- 11850746
TI  - Slow component of [V]O(2) kinetics: the effect of training status, fibre type,
      UCP3 mRNA and citrate synthase activity.
AB  - OBJECTIVE: In healthy individuals performing constant-load exercise at
      intensities above the lactate threshold a secondary rise in pulmonary oxygen
      uptake ([V]O(2)) occurs. [V]O(2) reaches a maximum and exhaustion rapidly
      prevails for a range of work rates lower than the maximal work rate achieved
      during a conventional rapid-incremental test. This phenomenon is called the slow
      component (SC) of [V]O(2) kinetics and represents an increase in [V]O(2) without
      an increase in work rate. Although still under debate, the magnitude of the SC is
      believed to be associated with the percentage of type II muscle fibres and their
      recruitment. In this study we investigated the relationship between the magnitude
      of the relative SC, citrate synthase activity, UCP2 and UCP3 mRNA levels and
      muscle fibre composition in both endurance-trained and recreationally active
      subjects. METHOD: The magnitude of the relative SC was measured in 12 endurance
      trained (Tr) and 15 recreationally active (RA) male subjects. The magnitude of
      the relative SC was determined as the difference between the end-exercise [V]O(2)
      and 3 min [V]O(2) divided by the difference between end-exercise [V]O(2) and
      baseline [V]O(2). UCP2 and UCP3 mRNA expression in the vastus lateralis was
      measured by RT-PCR with beta-actin mRNA used as an internal control. These values
      were also normalized against cytochrome-b mRNA to control for training induced
      changes in mitochondria when comparing the Tr and RA groups. Type I, IIa and IIx
      skeletal muscle fibre composition was determined using a routine myosin ATPase
      histochemical staining technique. Citrate synthase (CS) activity was measured
      using spectrophotometric detection. RESULTS: The magnitude of the relative SC of
      the Tr group had the highest correlation with citrate synthase activity (r=-0.90,
      P<0.001) and that of the RA group with [V]O(2) peak (r=-0.68, P<0.01). For the Tr
      group other correlations with the magnitude of the relative SC included UCP3 mRNA
      levels (r=0.69, P<0.05) and the percentage of type I fibres (r=-0.58, P<0.05),
      while for the RA group they included UCP3 mRNA (r=0.58, P<0.05) and the
      percentage of type IIa muscle fibres (r=0.59, P<0.05). The Tr subjects had a
      lower relative SC (P=0.04) and a lower expression of UCP2 (P=0.04), and UCP3 mRNA
      (P=0.01) than the RA subjects. When the groups were combined the magnitude of the
      relative SC correlated with UCP3 mRNA (r=0.70, P<0.01), percentage of type IIa
      muscle fibres (r=0.60, P<0.01) and [V]O(2) peak (r=-0.73, P<0.01). Additionally
      UCP3 mRNA correlated with the percentage of type IIa muscle fibres (r=0.63,
      P<0.001). CONCLUSION: Citrate synthase activity and [V]O(2) peak are indicators
      of aerobic fitness. The high negative correlations between the magnitude of the
      relative SC and citrate synthase activity and [V]O(2) peak, of the Tr and RA
      subjects, respectively, suggests that the magnitude of the relative SC is
      inversely correlated with aerobic fitness. Additionally the correlations between
      UCP3 mRNA and the magnitude of the relative SC for both groups individually and
      combined suggest that the uncoupling activity of the UCP3 protein may also
      influence the magnitude of the relative SC.

PMID- 11850747
TI  - The effect of obesity on the ratio of type 3 17beta-hydroxysteroid dehydrogenase
      mRNA to cytochrome P450 aromatase mRNA in subcutaneous abdominal and intra
      abdominal adipose tissue of women.
AB  - OBJECTIVES: To investigate (1) whether type 3 17beta-hydroxysteroid dehydrogenase
      (17beta-HSD), the enzyme which catalyzes the conversion of androstenedione to
      testosterone in the testis, is co-expressed with P450aromatase in the
      preadipocytes of women, and (2) whether the relative expression of type 3 17beta
      HSD and aromatase varies in subcutaneous abdominal vs intra-abdominal adipose
      tissue of women. SUBJECTS: Subcutaneous abdominal and intra-abdominal adipose
      tissue was obtained from women undergoing elective abdominal surgery (age 22-78
      y, body mass index (BMI) 22.4-52.9 kg/m(2)). MEASUREMENTS: Expression of type 3
      17beta-HSD in adipose cell fractions was determined using RT-PCR. Preadipocyte
      steroidogenesis was investigated in primary cultures using androstenedione as
      substrate. Messenger RNA levels for type 3 17beta-HSD and aromatase were measured
      in adipose tissue from the subcutaneous abdominal and intra-abdominal depots
      using a quantitative multiplex competitive RT-PCR assay. RESULTS: Type 3 17beta
      HSD is co-expressed with aromatase in the abdominal preadipocytes of women.
      Cultured preadipocytes from both subcutaneous abdominal (n=5) and intra-abdominal
      (n=5) sites converted androstenedione to testosterone, and there was minimal
      conversion of androstenedione to estrone. Consistent with this, the levels of
      type 3 17beta-HSD mRNA were significantly higher than aromatase mRNA at both
      sites (P<0.05; n=8 subcutaneous abdominal, n=12 intra-abdominal adipose tissue).
      The ratio of levels of 17beta-HSD mRNA to aromatase mRNA in intra-abdominal
      adipose tissue was positively correlated with BMI (n=11, r=0.61, P<0.05) and
      waist circumference (n=10, r=0.65, P<0.05). The converse was found in
      subcutaneous abdominal adipose tissue. CONCLUSION: The intra-abdominal adipose
      tissue of women may be substantially androgenic, increasingly so with increasing
      obesity, particularly central obesity. While androgen production by this adipose
      tissue deposit may not contribute to circulating testosterone levels due to
      hepatic clearance, it may have hitherto unrecognised local effects in the intra
      abdominal adipose tissue and also on the liver via the hepatic portal system.
      These studies suggest a mechanism linking central obesity with insulin resistance
      and dyslipidaemia.

PMID- 11850748
TI  - Is adiposity at normal body weight relevant for cardiovascular disease risk?
AB  - OBJECTIVE: To examine the relation between adiposity and risk factors for
      cardiovascular disease (CVD) in normal weight (NW) individuals. METHODS: Cross
      sectional study using the sample of white people, aged from 17 to 60 y from the
      Quebec Family Study and the Heritage Family Study. NW subjects with a body mass
      index (BMI) between 18.5 and 25 kg/m(2) (181 males and 265 females) and
      overweight (OW) subjects with a BMI between 25 and 30 kg/m(2) (133 males and 114
      females) were retained for this study. NW subjects were divided into quintiles of
      each adiposity variable, then the quintiles and the OW group were evaluated for
      the presence of CVD risk factors. Using logistic regression analysis, the odds
      ratio (OR) for the prevalence of risk factors for each quintile of each adiposity
      variable and the OW group was estimated relative to the first quintile in NW
      subjects. Mean values of adiposity variables were compared between the subjects
      with and without risk factors. In these analyses, age and study cohort effects
      were taken into account. MEASUREMENTS: Percentage body fat (%fat) and fat mass
      (FM) measured by underwater weighing were available as adiposity variables. Risk
      factors included systolic and diastolic blood pressure, LDL and HDL cholesterol,
      triglycerides and fasting glucose. RESULTS: Wide ranges of values were observed
      for adiposity variables. HDL cholesterol, triglycerides and fasting glucose in NW
      males and HDL cholesterol in NW females were significantly correlated with all
      adiposity variables. For males, higher quintiles of adiposity variables in the NW
      group and the OW group tended to have higher ORs compared to the first quintiles
      for the risk factor variables. The fifth quintiles of all adiposity variables had
      the highest ORs (3.15 for %fat and 3.77 for FM) and they were significantly
      different from the first quintiles. OW males had ORs similar to those of the
      fifth quintiles for the risk factor variables. On the other hand, for females,
      the relatively linear associations were less clear in the NW group. In NW males,
      the subjects with at least one risk factor had significantly higher %fat and FM
      than the subjects without risk factors. In NW females, no significant difference
      was observed for these adiposity variables between the subjects with and without
      risk factors. CONCLUSION: NW males with elevated adiposity had higher prevalence
      of risk factors than NW males with less adiposity and the prevalence in the
      former was rather similar to that seen in OW males. On the other hand, measures
      of adiposity added little additional information to the BMI classification of NW
      on CVD risk factors in females.

PMID- 11850749
TI  - Long-term effects of weight loss on pharmaceutical costs in obese subjects. A
      report from the SOS intervention study.
AB  - BACKGROUND: Although intentional weight reduction improves obesity-related
      comorbidities, the associations between weight reduction, medication and related
      costs are rarely studied. This study investigates the long-term effects of weight
      change on medication for diabetes and cardiovascular disease (CVD) in severely
      obese subjects. METHODS: In the intervention study Swedish Obese Subjects, 510
      surgically and 455 conventionally treated obese patients have so far been
      followed for 6 y. Changes in the use and costs of medication were analyzed in
      relation to treatment and weight change. RESULTS: In comparison with controls,
      larger fraction of surgically treated patients discontinued the use of medication
      for CVD and diabetes at 2 and 6 y (risk ratios 0.56-0.77). Among subjects not
      initially on medication, surgery reduced the frequency of started treatments
      (risk ratios 0.08-0.80). Relative weight loss >or=10% was necessary to reduce
      costs of medication for CVD and diabetes among subjects with such treatment at
      baseline. To reduce initiation of new treatment against the two conditions,
      weight loss >or=15% was required. Over 6 y, the average annual cost for diabetes
      and CVD medication increased by 463 SEK (96%) in subjects with weight loss <5%,
      and decreased by 39 SEK(8%) in the weight loss group >or=15%. CONCLUSION: Long
      term intentional weight loss is associated with reduced medication and medication
      costs for diabetes and CVD. The effects appear to be more marked among subjects
      who are initially on medication for these conditions, whereas greater weight
      reduction is needed to prevent new subjects from starting on medication.

PMID- 11850750
TI  - A pilot study of long-term effects of a novel obesity treatment: omentectomy in
      connection with adjustable gastric banding.
AB  - AIM: To determine whether visceral fat reduction in connection with bariatric
      surgery could improve weight loss and metabolic profile of obese subjects.
      PATIENTS AND METHODS: In a one-center, randomized and controlled pilot trial we
      assigned 50 subjects with severe obesity (body mass index >35 kg/m(2)) to either
      adjustable gastric banding (AGB) alone (11 men and 14 women), or AGB plus
      surgical removal of the total greater omentum (11 men and 14 women). The patients
      were followed at regular intervals for 2 y and examined at 0 and 24 months with
      respect to body composition and metabolic profile. RESULTS: No significant
      differences between control and omentectomized patients were observed at
      baseline. The removed greater omentum constituted 0.8+/-0.4% (mean+/-s.d.) of
      total body fat. At 2 y follow-up there was an expected decrease in body weight
      and an improvement in metabolic profile in both groups. Although omentectomized
      subjects tended to lose more weight than control subjects the difference was not
      statistically significant and changes in waist-to-hip ratio and saggital diameter
      did not differ between groups. However, the improvements in oral glucose
      tolerance, insulin sensitivity and fasting plasma glucose and insulin were 2-3
      times greater in omentectomized as compared to control subjects (P from 0.009 to
      0.04), which was statistically independent of the loss in body mass index. No
      differences in blood lipids between the groups were recorded. No adverse effects
      related to omentectomy were observed. CONCLUSIONS: Omentectomy, when performed
      together with AGB, has significant positive and long-term effects on the glucose
      and insulin metabolic profiles in obese subjects.

PMID- 11850751
TI  - Energy and fat intake in obese and lean children at varying risk of obesity.
AB  - OBJECTIVE: This study compared lean children at high risk (HR) and low risk (LR)
      of obesity and obese children (OB) to assess the relationship between their
      energy (EI) and fat intake and adiposity. DESIGN: Cross-sectional study of energy
      and fat intake in children, using 7-day weighed intakes validated by doubly
      labelled water (DLW) energy expenditure. SUBJECTS: A total of 114 pre-pubertal
      children, 50 HR (mean+/-s.d., 6.7+/-0.6 y, 25.7+/-4.8 kg, 21.3+/-6.6% body fat),
      50 LR (mean+/-s.d., 6.6+/-0.8 y, 23.6+/-3.7 kg, 18.9+/-5.7% body fat) and 14 OB
      (mean+/-s.d., 6.8+/-1.0 y, 37.7+/-5.3 kg, 34.8+/-5.6% body fat). MEASUREMENTS:
      Body fatness was measured using deuterium dilution, total energy expenditure
      (TEE) by DLW and dietary intake using 7-day weighed records. RESULTS: EI was 98%
      of TEE in LR children, 95% in HR children and 86% in OB children. Although EI was
      similar in each group (LR, 7.03+/-1.26 MJ/day; HR, 7.30+/-1.46 MJ/day; OB, 7.55+/
      1.67 MJ/day), obese +/-4.6%; P<0.05). There was a significant linear trend
      towards increasing fat intake (percentage energy) with increasing risk of obesity
      (P<0.05). While HR children were heavier and fatter than LR children (P<0.05),
      their EI and fat intake were not significantly greater (HR, 73+/-17 g, 37.3+/
      4.4%). Dietary fat intake (percentage energy) was weakly but significantly
      related to body fatness (r(2)=0.05, P=0.02) by step-wise regression. Since energy
      from fat was the only macronutrient that was a significant predictor of body
      fatness, results were therefore analysed using quartiles of fat intake
      (percentage energy) as cut-offs. When grouped in this way children with the
      lowest intakes were leaner than those with the highest intakes (19.5+/-7.5 vs
      24.9+/-9.4% body fatness; P<0.05). There was a significant trend for increasing
      fatness as fat intake increased (P<0.05). CONCLUSION: Fat intake is related to
      body fatness in childhood.

PMID- 11850752
TI  - Threshold values of visceral fat measures and their anthropometric alternatives
      for metabolic derangement in Japanese obese boys.
AB  - OBJECTIVE: To determine whether the direct measure of visceral adipose tissue
      (VAT) by computed tomography (CT) is a superior diagnostic criterion to the
      anthropometric surrogates and more classical criteria of obesity. DESIGN: Cross
      sectional, clinical study. Obese boys were classified according to the occurrence
      of abnormal values in either serum triglyceride, alanine aminotransferase or
      insulin level. A threshold value of each criterion for such metabolic derangement
      was calculated, using the analysis of receiver operating characteristic (ROC)
      curve. SUBJECTS: Seventy-five consecutive outpatient Japanese obese boys, ranging
      in age from 6 to 14 y, were studied. MEASUREMENTS: Anthropometric indices
      measured were height, body weight, waist girth, hip girth, triceps and
      subscapular skinfold thicknesses. Classical criteria for obesity used were
      percentage overweight (POW), body mass index (BMI) and percentage body fat. Waist
      girth, sagittal diameter by CT and waist-hip ratio (WHR) were evaluated as
      anthropometric surrogates for VAT. The areas of total abdominal fat (TAF), VAT
      and subcutaneous adipose tissue (SAT) were measured by CT at the level of the
      umbilicus. Clinical blood biochemistry was analyzed in fasting blood samples of
      obese boys. RESULTS: Thirty-three boys were classified into a no-complication
      group, and 42 into a complication group. TAF, VAT and SAT areas were closely
      associated with age, body size and degree of overweight and adiposity, while
      VAT/SAT was not. VAT area, sagittal diameter, TAF area and waist girth were
      closely correlated with alanine aminotransferase, insulin, TG and HDL-C. VAT/SAT,
      BMI, SAT area, WHR, percentage body fat and POW were less closely associated with
      these biochemical indices. The descending order of the values of area under the
      curve for the ROC curves were as follows: VAT>sagittal diameter>TAF>VAT/SAT>waist
      girth>BMI>WHR>percentage body fat>POW. Both VAT area and VAT/SAT gave >80% of
      sensitivity and specificity. Among the anthropometric indices studied, the
      sagittal diameter was the best surrogate of visceral fat measure. The sensitivity
      and specificity for the rest of the anthropometric indices were in an
      unsatisfactory range. The threshold values for VAT area, VAT/SAT and sagittal
      diameter were 58.0 cm(2), 0.276 and 19.2 cm, respectively. CONCLUSION: The
      threshold values for VAT area, VAT/SAT and sagittal diameter for detecting
      biochemical complication in Japanese obese boys were lower than the respective
      values reported in adults. These values can be used for classifying the obese
      boys into two types: those with medical problem and those without.

PMID- 11850753
TI  - Prevalence and risk factors for overweight and obesity in children from
      Seychelles, a country in rapid transition: the importance of early growth.
AB  - OBJECTIVES: To establish the prevalence of overweight and obesity and related
      risk factors in children from Seychelles (Indian Ocean), a country in rapid
      economic and epidemiological transition. DESIGN: Cross-sectional study with
      retrospective access to early life data. SUBJECTS: All children from all schools
      of Seychelles, in four selected school grades (kindergarten, fourth, seventh and
      tenth year of obligatory school) in 1999. A total of 5514 children aged 4.5-17.4
      y were measured, corresponding to 83.5% of the eligible population. MEASUREMENTS:
      Overweight and obesity, using age- and sex-specific body mass index (BMI) cut-off
      points as defined by the International Obesity Task Force. RESULTS: Some 12.6%
      (95% confidence interval: 11.8-13.5%) of the children were overweight and 3.8%
      (3.3-4.4%) were obese. Weight gain (kg) during the first year of life was
      strongly associated with subsequent overweight (odds ratio 1.46, 95% confidence
      interval 1.27-1.67) and obesity (1.59, 1.29-1.97) in childhood, independently of
      birth weight. Increased maternal BMI (kg/m(2)) was also associated with
      overweight (1.07, 1.03-1.10) and obesity (1.09, 1.04-1.14) in the offspring.
      CONCLUSION: Prevalence of overweight and obesity among school children in
      Seychelles was as high as or higher than in some industrialized countries. If
      confirmed in other environments, the strong association between weight gain
      during the first year of life and subsequent obesity in childhood could affect
      the way optimal infant weight gain is defined in countries where public health
      priorities are changing.

PMID- 11850754
TI  - The hormone-sensitive lipase gene and body composition: the HERITAGE Family
      Study.
AB  - OBJECTIVE: To investigate whether the C-60G polymorphism and other markers in the
      hormone-sensitive lipase (LIPE) gene are associated with baseline body
      composition and free-fatty acid (FFA) concentrations measured at rest and during
      low-intensity exercise in white and black subjects participating in the HERITAGE
      Family Study. SUBJECTS: Adult sedentary white (245 men and 258 women) and black
      (91 men and 185 women) subjects. MEASUREMENTS: body mass index (BMI); fat mass
      (FAT); percentage body fat (%FAT); fat-free mass (FATFR); sum of eight skinfolds
      (SF8); subcutaneous (ASF), visceral (AVF) and total (ATF) abdominal fat areas
      assessed by CT scan; plasma FFA concentrations measured at rest (FFAR), at a
      power output of 50 W (FFA50) and at a relative power output of 60% of VO(2max)
      (FFA60%); and fasting insulin (INS). STATISTICAL ANALYSIS: Association between
      the C-60G polymorphism of the LIPE gene and each phenotype was tested separately
      in men and women using ANCOVA with the effects of age and race as covariates and
      with further adjustment for FAT for ASF, AVF, ATF, FFAR, FFA50 and FFA60%.
      Secondly, owing to significant gene-by-race interaction, associations were
      investigated separately in each of the two race groups. Linkage was tested with
      the C-60G polymorphism, a dinucleotide repeat polymorphism in the intron 7 of the
      LIPE gene and two microsatellites markers (D19S178 and D19S903) flanking the LIPE
      gene. RESULTS: There were no race differences in the allele frequencies of the C
      60G polymorphism of the LIPE gene. No association or gene-by-race interaction was
      observed in men. However, in women, strong gene-by-race interactions were
      observed for BMI (P=0.0005), FAT (P=0.0007), %FAT (P=0.0003), SF8 (P=0.0001), ASF
      (P=0.03) and ATF (P=0.01). When the analysis was performed separately in each
      race, white women carriers of the -60G allele exhibited lower %FAT (P=0.005) and
      SF8 (P=0.01) than non-carriers, while in black women, the -60G allele was
      associated with higher BMI (P=0.004), FAT (P=0.009), %FAT (P=0.01) and SF8
      (P=0.0009). These associations were no longer significant after adjusting for
      INS. Evidence of linkage was observed in whites with ATF, FFAR, FFA50 and FFA60%.
      CONCLUSION: These results suggest that the C-60G polymorphism in the LIPE gene
      plays a role in determining body composition and that its effect is sex-, race-
      and insulin-dependent.

PMID- 11850755
TI  - Segregation analysis of waist circumference, hip circumference and waist-to-hip
      ratio in the Korean Nationwide Family Study.
AB  - AIM: A central distribution of adipose tissue is frequently associated with
      cardiovascular disease and its risk factors. In this study, we investigated
      environmental, familial and genetic influences on waist circumference (WC), hip
      circumference (HC) and waist-to-hip ratio (WHR) in 2507 members of 435 families
      who had participated in the Korean Nationwide Health Examination Survey. METHOD:
      Maximum likelihood methods were used to fit several genetic and nongenetic models
      of inheritance to these data to determine whether an unobserved Mendelian major
      gene could explain the familial distribution of WC, HC and WHR. Adjustments for
      age, age(2), body mass index, smoking, alcohol consumption and exercise were
      carried out separately for males and females by multiple regression procedures
      for WC, HC and WHR phenotypes prior to segregation analysis. Regression models
      were used to test genetic and non-genetic models in these 435 families. RESULTS:
      Segregation analysis did not provide statistical evidence of a major gene
      controlling either HC or WHR. Mendelian single-locus models with two underlying
      genotypic distributions were best supported by these data on WC, and this
      putative major gene explained the 22.4% of variance in adjusted WC. CONCLUSION:
      Future linkage studies may be worthwhile to further clarify the mechanisms
      controlling WC.

PMID- 11850756
TI  - Neighbourhood deprivation and overweight: the GLOBE study.
AB  - BACKGROUND: Increasing morbidity and mortality rates of coronary heart disease
      (CHD) by increasing levels of neighbourhood deprivation may be explained by a
      positive association between neighbourhood deprivation and risk factors of CHD.
      In this study we investigated the association between neighbourhood deprivation
      and overweight. Further, we examined whether this association was modified by
      educational level, age and sex of the neighbourhood residents. METHODS: Data were
      used from 8897 subjects who participated in the baseline measurement of the Dutch
      GLOBE Study in 1991 and lived in 86 neighbourhoods of the fifth largest city in
      The Netherlands (Eindhoven). Neighbourhood deprivation was based on aggregated
      self-reported information about educational and occupational level and employment
      status. Self-reported body height and body weight were used to define overweight
      body mass index ((BMI) >or=25). RESULTS: Adjusted for educational level, age and
      sex of neighbourhood residents, odds ratios of overweight increased significantly
      by increasing neighbourhood deprivation (odds ratio=1.20, 95% CI 1.02, 1.41 in
      the highest vs lowest quartile of neighbourhood deprivation). Stratified analyses
      showed a stronger association between neighbourhood deprivation and overweight in
      females compared to males, and in older (>or=49 y of age) compared to younger
      participants. The pattern of increasing odds ratios of overweight by
      neighbourhood deprivation was generally similar in all educational groups, the
      highest educational group being the exception with no association between
      neighbourhood deprivation and overweight. CONCLUSIONS: Increased prevalence rates
      of overweight in more compared to less deprived neighbourhoods are likely to
      contribute to the positive association between neighbourhood deprivation and CHD.
      Our results justify the development of a community-based strategy of primary
      prevention of overweight in deprived neighbourhoods, which may have a larger
      impact in females and older residents in particular. Prior to implementation,
      however, longitudinal research needs to further examine responsible mechanisms
      for the development of neighbourhood inequalities in overweight.

PMID- 11850757
TI  - Spousal resemblance in the Canadian population: implications for the obesity
      epidemic.
AB  - OBJECTIVE: To determine the extent of the spousal resemblance for adiposity and
      leanness in the Canadian population. DESIGN: Cross-sectional population survey.
      METHODS: The sample comprised parents and offspring from 1341 families (n=4023)
      of the Canada Fitness Survey. Indicators of adiposity included the body mass
      index (BMI) and the sum of five skinfolds (SF5). Both offspring and parents were
      ranked by their BMI and SF5 percentile position in the population using the
      entire Canada Fitness Survey database (n=15 818). RESULTS: Pearson correlations
      indicated significant spousal resemblance for both BMI (r=0.14; P<0.0001) and SF5
      (r=0.13; P<0.0001). However, the magnitude of the spousal correlations varied by
      the adiposity status of the offspring, with spousal correlations tending to be
      stronger in parents of lean or obese children and lower among parents of
      'average' children. Bivariate histograms indicated that among lean (<or=5th
      percentile) and obese offspring (>or=95th percentile), the parental pairs tended
      to cluster among the lower and higher percentiles of adiposity, respectively.
      CONCLUSIONS: There are spousal similarities in adiposity, particularly among
      parents of lean or obese offspring in the Canadian population. The degree to
      which these similarities are due to a loading of spouses with genes predisposing
      to obesity or a shared household environment cannot be determined from the
      present study. However, these results are compatible with the notion that genes
      and mutations predisposing to obesity are more prevalent among obese parents
      while those for pronounced leanness are more prevalent among lean parents.

PMID- 11850758
TI  - The relationship of overweight and obesity with subjective health and use of
      health-care services among Spanish women.
AB  - OBJECTIVE: To examine the relationship of overweight and obesity with subjective
      health and use of health-care services among women in Spain. METHODS: Data were
      drawn from the 1993 Spanish National Health Survey, covering a 13 244-woman
      sample representative of the non-institutionalised Spanish population aged 16 y
      and over. Information was collected through home-based interviews. Multiple
      logistic regression models were used to calculate odds ratios for suboptimal
      health (fair, poor or very poor) and utilisation of health-care services by women
      with normal weight (BMI 18.5-24.9 kg/m(2)), overweight (BMI 25.0-29.9 kg/m(2))
      and obesity (BMI>or=30 kg/m(2)). Analyses were adjusted for age, education level,
      occupation, civil status, social support, tobacco use, alcohol consumption,
      physical activity at work and during leisure time, job status and town of
      residence. RESULTS: Frequency of suboptimal health was higher in women with
      overweight (OR 1.7; 95% CI 1.5-1.9) and obesity (OR 2.1; 95% CI 1.8-2.5) than in
      those with normal weight. Overweight and obese women visited the physician, used
      hospital emergency services and took medication with greater frequency than did
      women of normal weight. There was a positive dose-response relationship (P<0.05)
      of BMI>or=18.5 kg/m(2) with suboptimal health and utilisation of health-care
      services. These associations were not wholly explained by BMI-related risk
      factors and chronic diseases, since their statistical significance remained
      unchanged and their magnitude was only slightly reduced after adjustment for
      those factors. The association of overweight and obesity with the use of health
      care services did not vary with age, educational level or presence of chronic
      disease. CONCLUSION: Overweight and obese women have worse subjective health and
      make greater use of health-care services. This finding is an additional argument
      for implementing weight-control programmes in Spain.

PMID- 11850759
TI  - Multiple symmetric lipomatosis: clinical aspects and outcome in a long-term
      longitudinal study.
AB  - BACKGROUND: Multiple symmetric lipomatosis (MSL) is a rare disease characterized
      by the growth of uncapsulated masses of adipose tissue. MSL is associated with
      high ethanol intake and complicated by somatic and autonomic neuropathy and by
      the infiltration of the adipose tissue at the mediastinal level. To date, the
      disease is considered as slowly progressive, but long-term longitudinal data are
      still lacking. In this study, a long-term follow-up of a large series of MSL
      patients is presented. METHODS: We studied 31 patients with MSL (30 males and one
      female) first evaluated at our institution from 1973 to 1992. All patients were
      followed until 1998-1999 or until death, with a mean follow-up of 14.5+/-5.0 y
      (range 4-26 y). Both at baseline and during follow-up, the location and the size
      of the subcutaneous lipomatous fat depots, the presence and the extension of
      deeply localized lipomatous tissue, and the presence and the severity of both
      somatic and autonomic neuropathy were evaluated. RESULTS: Eight MSL patients died
      during follow-up (25.8% of patients). A sudden death was proved to be the cause
      of death in three patients. All these three patients had severe autonomic
      neuropathy and none had coronary disease, acute myocardial infarction or other
      cardiac abnormalities. No signs or symptoms of coronary heart disease were
      present in the whole series. In addition to this high fatality rate, a
      substantial morbidity related to the occupation of the mediastinal space by the
      lipomatus tissue and to somatic neuropathy was also observed. CONCLUSIONS: MSL is
      associated with a significant morbidity and mortality. Therefore, the definition
      of 'benign symmetric lipomatosis', still adopted by several authors, cannot be
      justified.

PMID- 11850760
TI  - Pharmacotherapy for obesity: a quantitative analysis of four decades of published
      randomized clinical trials.
AB  - AIM: This article provides the first comprehensive meta-analysis of randomized
      clinical trials of medications for obesity. METHOD: Based on stringent
      inclusionary criteria, a total of 108 studies were included in the final
      database. Outcomes are presented for comparisons of single and combination drugs
      to placebo and for comparisons of medications to one another. RESULT: Overall,
      the medications studied produced medium effect sizes. Four drugs produced large
      effect sizes (ie d>0.80; amphetamine, benzphetamine, fenfluramine and
      sibutramine). The placebo-subtracted weight losses for single drugs vs placebo
      included in the meta-analysis never exceeded 4.0 kg. No drug, or class of drugs,
      demonstrated clear superiority as an obesity medication. Effects of
      methodological factors are also presented along with suggestions for future
      research.

PMID- 11850761
TI  - Decreased plasma orexin-A levels in obese individuals.
AB  - Orexin-A and -B stimulate appetite and food intake in rats. Orexins and orexin
      receptors are present in the hypothalamus as well as the enteric nervous system,
      the pancreas and the gut. The presence of orexins in peripheral blood, however,
      has not yet been reported. To determine whether orexin-A is present in human
      plasma and is related to body weight, we measured plasma orexin-A and leptin
      levels in a population with a body mass index (BMI) range from 19.8 to 59
      kg/m(2). Plasma orexin-A levels correlated negatively and plasma leptin levels
      correlated positively with BMI. In obese and morbidly obese individuals, orexin-A
      levels were significantly lower and leptin levels were significantly higher when
      compared to normal. Our results support previous data suggesting that orexin-A
      acts also in a peripheral manner. The fact that lower levels of plasma orexin-A
      are present in obese individuals suggests that it is involved in the regulation
      of human energy metabolism.

PMID- 11850762
TI  - Intermediate results of health related quality of life after vertical banded
      gastroplasty.
AB  - OBJECTIVES: The purpose of this study is to evaluate (a) health-related quality
      of life (HRQL) after vertical banded gastroplasty (VBG) (Mason) and (b)
      predictors of HRQL. SUBJECTS: Eighty-two consecutive patients were assessed
      preoperatively and then after 6, 12 and 24 months. Patients filled out
      questionnaires for subjective appraisal of HRQL (physical well-being, mood,
      physical performance, perceived health, social support and coping/adjustment).
      RESULTS: The greatest improvement in weight and HRQL was seen within 6 months of
      surgery. Twenty-four months after VBG weight reduction (P<0.05), perceived health
      (P<0.05), physical well-being (P<0.05), physical performance (P<0.05), mood
      (P<0.05), coping/adjustment (P<0.05) continued to be better than before surgery.
      Preoperative binge eating was the most important predictor of HRQL. CONCLUSION:
      Two years after VBG weight loss and a significant improvement of HRQL can be
      found. HRQL and weight loss are not associated in terms of outcome, indicating
      that weight loss alone may not be enough to improve HRQL.

PMID- 11850763
TI  - Fixed dose combination therapy in the treatment of hypertension.

PMID- 11850764
TI  - Microalbuminuria, an integrated marker of cardiovascular risk in essential
      hypertension.
AB  - This paper reviews the existing epidemiological and clinical evidence about the
      relationships of non-diabetic microalbuminuria with cardiovascular risk factors
      such as elevated blood pressure (BP), systolic particularly, cardiac hypertrophy,
      adverse metabolic status, smoking habits, elevated angiotensin II levels,
      endothelial dysfunction, acute and perhaps subclinical inflammation. Because of
      that unique property of reflecting the influence of so many clinically relevant
      parameters, microalbuminuria may legitimately be defined as an integrated marker
      of cardiovascular risk, an unique profile among the several prognostic predictors
      available to stratify risk in hypertensive patients. Recent cohort studies also
      showed associations with cardiovascular morbidity and mortality independently
      from conventional atherogenic factors. This behaviour, whose understanding still
      needs further elucidation, suggests to measure albuminuria and to screen patients
      at a higher absolute risk in whom preventive treatment is expected to be more
      beneficial than in those with a lower absolute risk.

PMID- 11850765
TI  - An association between smoking habits and blood pressure in normotensive Japanese
      men.
AB  - We conducted a cross-sectional study to clarify the dose-effect relationship of
      smoking habits with blood pressure in Japanese men. The subjects were 2781
      normotensive male steelworkers ranging in age from 40 to 54 years. They were
      classified into five categories according to their smoking habits: non-smokers,
      ex-smokers, light smokers, moderate smokers and heavy smokers. Age, body mass
      index, salt intake, physical activity, drinking habits, and levels of gamma
      glutamyl transpeptidase, total serum cholesterol, uric acid, creatinine and
      plasma glucose were analysed as covariates. The association between smoking
      habits and blood pressure was evaluated using analysis of covariance. Our results
      showed that there was no significant difference in the adjusted systolic and
      diastolic blood pressure between non-smokers and ex-smokers. The adjusted
      systolic and diastolic blood pressures in light, moderate and heavy smokers were
      significantly lower than in non- and ex-smokers. However, among smokers, no
      significant difference was observed in correlation with smoking amount. In
      conclusion, blood pressure of smokers was lower than that of non- and ex-smokers.
      However, there were no significant dose-effect relationships between smoking
      amount and blood pressure when lifestyle and other confounding factors were
      considered.

PMID- 11850766
TI  - A simple method to estimate populational 24-h urinary sodium and potassium
      excretion using a casual urine specimen.
AB  - In order to estimate the salt and potassium intake in a population and to compare
      their annual trends, we developed a simple method to estimate population mean
      levels of 24-h urinary sodium (24HUNaV) and potassium (24HUKV) excretion from
      spot urine specimens collected at any time. Using 591 Japanese data items from
      the INTERSALT study as a gold standard, we developed formulas to estimate 24-h
      urinary creatinine (24HUCrV), 24HUNaV and 24HUKV using both spot and 24-h urine
      collection samples. To examine the accuracy of the formulas, we applied these
      equations to 513 external manual workers. The obtained formulas were as follows:
      (1) PRCr (mg/day) = -2.04 x age + 14.89 x weight (kg) + 16.14 x height (cm) 
      2244.45; (2) estimated 24HUNaV (mEq/day) = 21.98 x XNa (0.392); (3) estimated
      24HUKV (mEq/day) = 7.59 x XK(0.431); where PRCr = predicted value of 24HUCr, SUNa
      = Na concentration in the spot voiding urine, SUK = K concentration in the spot
      voiding urine, SUCr = creatinine concentration in the spot voiding urine, XNa (or
      XK) = SUNa (or SUK)/SUCr x PRCr. In the external group, there was a significant
      but small difference between the estimated and measured values in sodium (24.0
      mmol/day) and potassium (3.8 mmol/day) excretion. In every quintile divided by
      the estimated 24HUNaV or 24HUKV, the measured values were parallel to the
      estimated values. In conclusion, although this method is not suitable for
      estimating individual Na and K excretion, these formulas are considered useful
      for estimating population mean levels of 24-h Na and K excretion, and are
      available for comparing different populations, as well as indicating annual
      trends of a particular population.

PMID- 11850768
TI  - Prognostic value of blood pressure in acute stroke.
AB  - Manipulation of blood pressure (BP) in acute stroke may improve outcome. Despite
      various studies, data on the prognostic significance of early BP in stroke remain
      unclear. Therefore, we studied the relationship between various BP variables in
      the acute phase of stroke and functional outcome at 3 months. Blood pressures
      were collected by reviewing BP records of 817 patients who were admitted to our
      stroke unit between 1987 and 1992. Besides the first systolic and diastolic
      admission BP (SBP and DBP), we also used the mean of the daytime as well as the
      night-time systolic and diastolic BP values. Finally, we studied the relationship
      between the decrease in BP between day 0 and 4 and outcome. As dependent outcome
      variable we used the Rankin handicap score at 3 months dichotomized in a score >3
      (poor outcome) vs a score 3 (good outcome). A total of 430 patients were admitted
      within 24 h following stroke onset. There was no significant relationship between
      the systolic and diastolic BP and the outcome at 3 months. Only night-time
      systolic BP 165 mm Hg (odds ratio (OR) 2.8; 95% CI 1.1-6.8), night-time diastolic
      BP 60 mm Hg (OR 8.1; 95% CI 1.1-58.3), and a decrease in daytime diastolic BP
      between day 0 and 4 of 10 mm Hg (OR 3.0; 95% CI 1.1-7.9) showed a significant
      relationship with poor outcome. Our findings suggest that admission BP values may
      not reliably reflect any impact of BP on stroke outcome. They also suggest a
      potential differential effect of BP manipulation: increasing or decreasing BP may
      be beneficial for patients with BP extremes in one direction, but detrimental for
      those with BP values in the opposite direction.

PMID- 11850767
TI  - A cross-sectional study on association of calcium intake with blood pressure in
      Japanese population.
AB  - To investigate the association of calcium intake independently of other nutrients
      already known as predictors of hypertension, a cross-sectional study was carried
      out on the same population in Japan as used for the INTERSALT study. Dietary
      calcium intake was estimated from a 1-day 24-h recall. Sodium and potassium
      intakes were evaluated by 24-h urinary excretion. Data from 476 subjects aged 20
      59 years, 230 men and 246 women, were analysed. The mean dietary calcium intake
      ranged from 557 to 608 mg/day among men, and from 528 to 639 mg/day among women.
      Among men, the pooled estimate of the regression coefficients of blood pressure
      (mm Hg) per 100 mg increase of calcium intake, adjusted for age and body mass
      index (BMI), were -0.42 mm Hg for systolic blood pressure (SBP) and -0.35 mm Hg
      for diastolic blood pressure (DBP), but there was no statistical significance.
      Among women, the pooled estimates of regression coefficients adjusted for age and
      BMI were -0.92 mm Hg for SBP and -0.83 mm Hg for DBP with statistical
      significance. After adjustment for age, BMI, alcohol intake and urinary excretion
      of sodium and potassium, the pooled estimate of calcium intake was -0.66 mm Hg
      for DBP with statistical significance and -0.70 mm Hg for SBP. A significant
      negative association of calcium intake with blood pressure was observed among the
      subjects in Osaka. Our study suggests that increased calcium intake may provide a
      benefit of lowering blood pressure independently of other minerals such as sodium
      and potassium.

PMID- 11850769
TI  - Left ventricular mass and systolic dysfunction in essential hypertension.
AB  - A relation between left ventricular (LV) hypertrophy and depressed midwall
      systolic function has been described in hypertensive subjects. However, a strong
      confounding factor in this relation is concentric geometry, which is both a
      powerful determinant of depressed midwall systolic function and a correlate of LV
      mass in hypertension. To evaluate the independent contribution of LV mass to
      depressed systolic function, 1827 patients with never-treated essential
      hypertension (age 48 +/- 12 years, men 58%) underwent M-mode echocardiography
      under two-dimensional guidance. Relative wall thickness was the strongest
      determinant of low midwall fractional shortening (r = -0.63, P < 0.0001). The
      significant inverse relation observed between LV mass and midwall fractional
      shortening (r = -0.43, P < 0.0001) persisted after taking into account the effect
      of relative wall thickness (partial r = -0.27, P < 0.0001). Within each sex
      specific quintile of relative wall thickness, prevalence of subnormal afterload
      corrected midwall systolic function was greater in subjects with, than in
      subjects without, LV hypertrophy (P < 0.05 for the first, third, fourth and fifth
      quintile). In a multiple linear regression analysis, both LV mass (P < 0.0001)
      and relative wall thickness (P < 0.0001) were independent predictors of a reduced
      midwall fractional shortening. In conclusion, the inverse association between LV
      mass and midwall systolic function is partly independent from the effect of
      relative wall thickness. LV hypertrophy is a determinant of subclinical LV
      dysfunction independently of the concomitant changes in chamber geometry.

PMID- 11850770
TI  - An epidemiological re-appraisal of the association between blood pressure and
      blood lead: a meta-analysis.
AB  - Studies on the possible association between blood pressure and blood lead have
      reached divergent conclusions. In a previous meta-analysis, a doubling of the
      blood lead concentration was associated with a 1.0/0.6 mm Hg increase in systolic
      and diastolic blood pressure (BP). This meta-analysis updates the analysis
      originally performed in 1994. Articles on the association between BP and blood
      lead were identified from computer searches from January 1980 to February 2001
      using the Medical Literature Analysis and Retrieval System. Of the studies
      reviewed, 31 provided sufficient details to be considered. The meta-analysis
      included 58518 subjects recruited from the general population in 19 surveys and
      from occupationally exposed groups in 12 studies. In all but four studies, the
      results were adjusted for age, and most studies took into account additional
      confounding factors such as body mass index and the use of alcohol and
      medication. Weighted joint P-values were calculated using Stouffer's procedure.
      The association between BP and blood lead was similar in both men and women. In
      the combined studies, a two-fold increase in blood lead concentration was
      associated with a 1.0 mm Hg rise in the systolic pressure (95% CI +0.5 to +1.4 mm
      Hg; P < 0.001) and with a 0.6 mm Hg increase in the diastolic pressure (95% CI
      +0.4 to +0.8 mm Hg; P < 0.001). On balance, this meta-analysis suggests that
      there can only be a weak association between BP and blood lead.

PMID- 11850771
TI  - Comparative effects of chronic ACE inhibition and AT1 receptor blocked losartan
      on cardiac hypertrophy and renal function in hypertensive patients.
AB  - The present study describes the effects of losartan and the angiotensin
      converting enzyme inhibitor enalapril on blood pressure, echocardiographically
      calculated left ventricular mass, renal function evaluated by glomerular
      filtration rate and quality of life. The renin-angiotensin-aldosterone system is
      of importance for cardiovascular growth. There is substantial experimental
      documentation in animals that the angiotensin II antagonist, losartan, decreases
      the cardiac hypertrophy response caused by elevated arterial pressure as well as
      intravascular volume overload. However, data in humans is scarce. This is a 3
      year, randomised, double-blind study with parallel group design in 50 patients
      with essential hypertension. The results show that both drugs reduced blood
      pressure equally effectively, and also left ventricular mass (P < 0.001). After 3
      years of treatment glomerular filtration rate significantly increased with
      losartan (P < 0.005). Serum uric acid fell modestly although significantly, dose
      dependent in losartan patients compared with an increase in enalapril patients. A
      fall in serum potassium from the pre-study period was observed in all patients.
      There was no difference between treatments in terms of patient satisfaction on
      quality of life. Both drugs have relatively similar hormonal and haemodynamic
      effect, with an excellent tolerability profile; they appear to induce comparable
      blood pressure falls in hypertensive patients in particular, therapy based on
      specific Ang II blockade may offer advantages in high risk hypertensives if left
      ventricular hypertrophy is present. Both enalapril and losartan, in improving the
      renal function attenuating the intrarenal effects of angiotensin II, might be
      able to reverse the pathophysiology of essential hypertensive kidney disease, and
      should be first-choice drugs in the treatment of essential hypertension.

PMID- 11850772
TI  - Office blood pressure variability as a predictor of acute myocardial infarction
      in elderly patients receiving antihypertensive therapy.
AB  - Larger variability of office blood pressure (BP) was reportedly associated with a
      higher risk of stroke or mortality from all causes. In the present study, we
      focused on the relationship of variability of office BP and occurrence of acute
      myocardial infarction (MI). We registered 139 patients receiving antihypertensive
      therapy for more than 1 year who experienced first-ever episode of MI at the age
      of 60 years or over. At least two sex- and age-matched (+/- 5 years) control
      patients were registered for every MI patient. Average systolic and diastolic BP
      during the 12-month period prior to the occurrence of MI, or the time of
      registration in the case of control patients, was similar in both patient groups.
      The office BP variability was evaluated by calculating the variation coefficient
      (VC) of BP. VC of diastolic BP was significantly higher in the MI patients (10.0
      +/- 4.0%) compared with the control patients (8.8 +/- 3.4%). VC of systolic BP
      was not different between the MI and the control patients. Multiple logistic
      analysis revealed the relationship of the VC for office diastolic BP to the
      occurrence of MI was significant after adjustment for BP level, age, gender, body
      mass index, serum total cholesterol concentrations, diabetes mellitus, and
      current smoking. In conclusion, larger long-term variability of office diastolic
      BP during antihypertensive therapy is a predictor of MI.

PMID- 11850774
TI  - Telomerase is not an oncogene.
AB  - In the decade since the telomere hypothesis of cellular aging was proposed, the
      two essential genes for human telomerase were cloned and characterized, allowing
      experimental proof of the causal relationships between telomere loss and
      replicative senescence, and telomerase activation and immortalization. These
      relationships were established using a variety of cultured human cell types from
      both normal and tumor tissues, and were largely confirmed in the telomerase
      knockout mouse. Taken together, the data provide strong support for the potential
      utility of telomerase detection and inhibition for cancer, and telomerase
      activation for degenerative diseases. The specificity of the promoter for the
      telomerase catalytic gene and the antigenicity of the protein product, hTERT,
      provide additional strategies for killing telomerase-positive tumor cells.
      Unfortunately, the strong link between telomerase and cancer has led some to
      confuse telomerase activation with cancer, and others to overstate the cancer
      risk of telomerase activation therapies for degenerative diseases. This review
      clarifies the difference between telomerase, which does not cause growth
      deregulation, and oncogenes, which do. It also addresses the concept of
      telomerase repression as a tumor suppressor mechanism early in life, with
      detrimental tissue degeneration and tumor-promoting consequences late in life.
      This extended view of the telomere hypothesis helps explain how telomerase
      inhibition can be therapeutic in cancer patients, while controlled telomerase
      activation for degenerative diseases may actually reduce, rather than increase,
      the frequency of age-related tumorigenesis.

PMID- 11850775
TI  - Telomeres, aging and cancer: in search of a happy ending.
AB  - Telomeres are distinctive structures, composed of a repetitive DNA sequence and
      associated proteins, that cap the ends of linear chromosomes. Telomeres are
      essential for maintaining the integrity and stability of eukaryotic genomes. In
      addition, under some circumstances, telomeres can influence cellular gene
      expression. In mammals, the length, structure, and function of telomeres have
      been proposed to contribute to cellular and organismal phenotypes associated with
      cancer and aging. Here, we discuss what is known about the basis for the links
      between telomeres, aging and cancer, and some of the known and proposed
      consequences of telomere dysfunction and maintenance for mammalian cells and
      organisms.

PMID- 11850776
TI  - Transcriptional silencing at Saccharomyces telomeres: implications for other
      organisms.
AB  - Telomeres are the natural ends of eukaryotic chromosomes. In most organisms,
      telomeres consist of simple, repeated DNA with the strand running 5' to 3'
      towards the end of the chromosome being rich in G residues. In cases where the
      very end of the chromosome has been examined, the G-strand is extended to form a
      short, single stranded tail. The chromatin structure of telomeric regions often
      has features that distinguish them from other parts of the genome. Because
      telomeres protect chromosome ends from degradation and end-to-end fusions and
      prevent the loss of terminal DNA by serving as a substrate for telomerase, they
      are essential for the stable maintenance of eukaryotic chromosomes. In addition
      to their essential functions, telomeres in diverse organisms are specialized
      sites for gene expression. Transcription of genes located next to telomeres is
      repressed, a phenomenon termed telomere position effect (TPE). TPE is best
      characterized in the yeast Saccharomyces cerevisiae. This article will focus on
      the silencing properties of Saccharomyces telomeres and end with speculation on
      the role of TPE in yeasts and other organisms.

PMID- 11850777
TI  - Telomere maintenance without telomerase.
AB  - Recombination-dependent maintenance of telomeres, first discovered in budding
      yeast, has revealed an alternative pathway for telomere maintenance that does not
      require the enzyme telomerase. Experiments conducted in two budding yeasts, S.
      cerevisiae and K. lactis, have shown recombination can replenish terminal G-rich
      telomeric tracts that would otherwise shorten in the absence of telomerase, as
      well as disperse and amplify sub-telomeric repeat elements. Investigation of the
      genetic requirements for this process have revealed that at least two different
      recombination pathways, defined by RAD50 and RAD51, can promote telomere
      maintenance. Although critically short telomeres are very recombinogenic,
      recombination among telomeres that have only partially shortened in the absence
      of telomerase can also contribute to telomerase-independent survival. These
      observations provide new insights into the mechanism(s) by which recombination
      can restore telomere function in yeast, and suggest future experiments for the
      investigation of potentially similar pathways in human cells.

PMID- 11850778
TI  - Protection of mammalian telomeres.
AB  - Telomeres allow cells to distinguish natural chromosome ends from damaged DNA.
      When telomere function is disrupted, a potentially lethal DNA damage response can
      ensue, DNA repair activities threaten the integrity of chromosome ends, and
      extensive genome instability can arise. It is not clear exactly how the structure
      of telomere ends differs from sites of DNA damage and how telomeres protect
      chromosome ends from DNA repair activities. What are the defining structural
      features of telomeres and through which mechanisms do they ensure chromosome end
      protection? What is the molecular basis of the telomeric cap and how does it act
      to sequester the chromosome end? Here I discuss data gathered in the last few
      years, suggesting that the protection of human chromosome ends primarily depends
      on the telomeric protein TRF2 and that telomere capping involves the formation of
      a higher order structure, the telomeric loop or t-loop.

PMID- 11850779
TI  - Regulation of the human telomerase reverse transcriptase gene.
AB  - Most somatic human cells lack telomerase activity because they do not express the
      telomerase reverse transcriptase (hTERT) gene. Conversely, most cancer cells
      express hTERT and are telomerase positive. For most tumors it is not clear
      whether hTERT expression is due to their origin from telomerase positive stem
      cells or to reactivation of the gene during tumorigenesis. Telomerase negative
      cells lack detectable cytoplasmic and nuclear hTERT transcripts; in telomerase
      positive cells 0.2 to 6 mRNA molecules/cell can be detected. This suggests that
      expression is regulated by changes in the rate of hTERT gene transcription. In
      tumor cell lines hTERT expression behaves like a recessive trait, indicating that
      lack of expression in normal cells is due to one or several repressors. Studies
      with monochromosomal hybrids indicate that several chromosomes may code for such
      repressors. A number of transcription factors, tumor suppressors, cell cycle
      inhibitors, cell fate determining molecules, hormone receptors and viral proteins
      have been implicated in the control of hTERT expression; but these studies have
      not yet provided a clear explanation for the tumor specific expression of the
      hTERT gene, and the cis-acting elements which are the targets of repression in
      normal cells still have to be identified.

PMID- 11850780
TI  - New ways not to make ends meet: telomerase, DNA damage proteins and
      heterochromatin.
AB  - Telomeres are stabilized, and telomeric DNA is replenished, by the action of the
      ribonucleoprotein reverse transcriptase telomerase. Telomere capping functions
      include the ability of telomeres to protect chromosome ends from cellular DNA
      damage responses such as cell cycle arrest or apoptosis. This property of
      telomeres is especially important for cancer cells, which continue proliferating
      despite chromosome aberrations. Telomere capping is influenced by multiple,
      mutually reinforcing factors including telomere length, although telomere length
      is only one of several determinants of telomere functionality. For example, many
      cancer cells express high levels of telomerase yet maintain relatively short
      telomeres. We consider three aspects of telomere capping that have emerged
      relatively recently: (1) a new role for telomerase in telomere capping
      independent of its function in telomere elongation. Support for this novel
      function comes from experiments showing an increase in replicative potential with
      the reactivation of telomerase, without net telomere lengthening; (2) the role at
      telomeres of DNA damage proteins. We propose a model in which two factors
      specifically target telomeres for the action of telomerase, as opposed to
      recombination or non-homologous end-joining: binding by telomeric proteins that
      limits DNA damage responses at telomeres, and the affinity of the telomerase RNP
      for telomeric proteins and DNA; and (3) we discuss a potential protective role of
      amplified subtelomeric DNAs, which may aid capping of telomeres maintained by non
      telomerase based mechanisms through the formation of heterochromatin.

PMID- 11850781
TI  - Telomerase in the human organism.
AB  - The intent of this review is to describe what is known and unknown about
      telomerase in somatic cells of the human organism. First, we consider the
      telomerase enzyme. Human telomerase ribonucleoproteins undergo at least three
      stages of cellular biogenesis: accumulation, catalytic activation and recruitment
      to the telomere. Next, we describe the patterns of telomerase regulation in the
      human soma. Telomerase activation in some cell types appears to offset
      proliferation-dependent telomere shortening, delaying but not defeating the
      inherent mitotic clock. Finally, we elaborate the connection between telomerase
      misregulation and human disease, in the contexts of inappropriate telomerase
      activation and telomerase deficiency. We discuss how our current perspectives on
      telomerase function could be applied to improving human health.

PMID- 11850782
TI  - A model for heterogeneous nuclear ribonucleoproteins in telomere and telomerase
      regulation.
AB  - The heterogeneous nuclear ribonucleoproteins (hnRNPs) are a large family of
      nucleic acid binding proteins that are often found in, but not restricted to, the
      40S-ribonucleoprotein particle. Subsets of hnRNPs are strictly nuclear while
      others shuttle between the nucleus and cytoplasm. Members of the hnRNP family
      have been implicated to have roles in many aspects of mRNA maturation/turnover
      and in telomere and telomerase regulation. Telomeres are repetitive DNA elements
      mainly found at the ends of human chromosomes. In most normal cells, telomeres
      shorten with each cell division. Telomere shortening can be compensated for by a
      ribonucleoprotein complex, called telomerase. Telomerase, consisting of an
      integral RNA and catalytic protein component as well as several auxiliary
      factors, extends the 3'-G-rich strand of the ends of the telomeres. Here we
      present new data and describe a model that implicates the telomerase bound hnRNPs
      in promoting telomere access by interacting with telomeres. Telomere bound hnRNPs
      include hnRNP A1, A2-B1, D and E and telomerase bound hnRNPs including hnRNPA1
      C1/C2 and D. The telomere and telomerase bound hnRNPs may prove to be good
      targets for regulating telomere length.

PMID- 11850783
TI  - Many ways to telomere dysfunction: in vivo studies using mouse models.
AB  - The existence of a capping structure at the extremities of chromosomes was first
      deduced in the 1930s by Herman Muller (Muller, 1938), who showed that X
      irradiation of Drosophila rarely resulted in terminal deletions or inversions of
      chromosomes, suggesting that chromosome ends have protective structures that
      distinguish them from broken chromosomes, which he named telomeres. In this
      review, we will focus on mammalian telomeres and, in particular, on the analysis
      of different mouse models for proteins that are important for telomere function,
      such as telomerase and various telomere-binding proteins. These murine models are
      helping us to understand the consequences of telomere dysfunction for cancer,
      aging and DNA repair, as well as, the molecular mechanisms by which telomeres
      exert their protective function.

PMID- 11850784
TI  - Telomere dysfunction: multiple paths to the same end.
AB  - The molecular cloning of telomerase and telomere components has enabled the
      analysis and precise manipulation of processes that regulate telomere length
      maintenance. In mammalian cells and in other organisms, we now recognize that
      disruption of telomere integrity via any one of a number of perturbations induces
      chromosome instability and the activation of DNA damage responses. Thus, telomere
      dysfunction may represent a physiological trigger of the DNA damage or apoptotic
      response in an analogous fashion to other genotoxic insults that introduce
      chromosome breaks. Initial studies in mice lacking the murine telomerase RNA and
      in cells expressing a dominant negative version of the telomere binding protein
      TRF2 revealed a strong p53-dependent response to telomere dysfunction. Yet,
      telomere dysfunction exhibits p53-independent effects as well, an observation
      supported by p53-independent responses to telomere dysfunction in p53 mutant
      human tumor cell lines and mouse cells. As most tumors are compromised for p53
      function, examination of this p53-independent response warrants closer attention.
      A better understanding of this p53-independent response may prove critical for
      determining the ultimate utility of telomerase inhibitors in the clinic. This
      review will summarize our current understanding of the molecular responses to
      telomere dysfunction in mammalian cells.

PMID- 11850785
TI  - Alternative lengthening of telomeres in mammalian cells.
AB  - Some immortalized mammalian cell lines and tumors maintain or increase the
      overall length of their telomeres in the absence of telomerase activity by one or
      more mechanisms referred to as alternative lengthening of telomeres (ALT).
      Characteristics of human ALT cells include great heterogeneity of telomere size
      (ranging from undetectable to abnormally long) within individual cells, and ALT
      associated PML bodies (APBs) that contain extrachromosomal telomeric DNA,
      telomere-specific binding proteins, and proteins involved in DNA recombination
      and replication. Activation of ALT during immortalization involves recessive
      mutations in genes that are as yet unidentified. Repressors of ALT activity are
      present in normal cells and some telomerase-positive cells. Telomere length
      dynamics in ALT cells suggest a recombinational mechanism. Inter-telomeric
      copying occurs, consistent with a mechanism in which single-stranded DNA at one
      telomere terminus invades another telomere and uses it as a copy template
      resulting in net increase in telomeric sequence. It is possible that t-loops,
      linear and/or circular extrachromosomal telomeric DNA, and the proteins found in
      APBs, may be involved in the mechanism. ALT and telomerase activity can co-exist
      within cultured cells, and within tumors. The existence of ALT adds some
      complexity to proposed uses of telomere-related parameters in cancer diagnosis
      and prognosis, and poses challenges for the design of anticancer therapeutics
      designed to inhibit telomere maintenance.

PMID- 11850786
TI  - ATM function and telomere stability.
AB  - Accumulation of DNA damage has been associated with the onset of senescence and
      predisposition to cancer. The gene responsible for ataxia telangiectasia (A-T) is
      ATM (ataxia-telangiectasia mutant), a master controller of cellular pathways and
      networks, orchestrating the responses to a specific type of DNA damage: the
      double strand break. Based on the homology of the human ATM gene to the TEL1,
      MEC1 and rad3 genes of yeast, it has now been demonstrated that mutations in ATM
      lead to defective telomere maintenance in mammalian cells. While ATM has both
      nuclear and cytoplasmic functions, this review will focus on its roles in
      telomere metabolism and how ATM and telomeres serve as controllers of cellular
      responses to DNA damage.

PMID- 11850787
TI  - Balancing instability: dual roles for telomerase and telomere dysfunction in
      tumorigenesis.
AB  - Telomere shortening and telomerase activation both occur in human tumors.
      Telomere shortening has been proposed to have two conflicting roles in
      tumorigenesis: tumor suppression and initiation of chromosomal instability.
      Similarly, while telomerase activation is suggested to be necessary for tumor
      growth, telomerase may help to stabilize genomic instability. Here we review what
      is known about these conflicting roles and propose a framework to understand the
      role of telomerase in cancer progression.

PMID- 11850788
TI  - Senescence: does it all happen at the ends?
AB  - Over 60 years ago Barbara McClintock described the telomere and suggested that it
      protected the chromosome from illegitimate or end-to-end fusion, thus functioning
      to protect the genome. Since that time we have discovered that the telomere is a
      complex structure composed of both DNA and a growing list of associated proteins
      that together serve to regulate the length of the telomere and, as predicted by
      McClintock, protect genomic integrity. In addition to its protective role, the
      telomere has also been hypothesized to serve as a molecular clock that tallies
      the number of cell divisions and limits further divisions at a predetermined
      point. However, the precise role of telomeres in predicting and limiting cellular
      lifespan remains a matter of much debate. In this review, we highlight some of
      the salient points of basic telomere biology and relate them to the current
      controversies surrounding the role of telomeres and telomerase in cellular
      senescence.

PMID- 11850789
TI  - Telomerase inhibition, oligonucleotides, and clinical trials.
AB  - Telomerase is expressed in most types of tumors but not in most somatic cells.
      This observation has led to two hypotheses; (i) telomerase activity is necessary
      for the proliferation of cancer cells; and (ii) telomerase inhibitors are a
      powerful strategy for cancer chemotherapy. Testing the latter hypothesis requires
      the development of potent and selective inhibitors of telomerase and their
      testing in clinical trials. Assaying the efficacy of telomerase inhibitors will
      not be simple because telomere erosion will be slow and antiproliferative effects
      will probably require weeks to become apparent. This review will describe the
      properties of 2'-O-alkyl oligonucleotide inhibitors of telomerase.
      Oligonucleotides that block expression of other cancer targets have favorable
      pharmacokinetic properties and are already in clinical trials. This experience is
      likely to facilitate clinical trials of anti-telomerase oligomers.

PMID- 11850790
TI  - Oligonucleotide N3'-->P5' phosphoramidates as efficient telomerase inhibitors.
AB  - Human telomerase is a unique reverse transcriptase that is expressed in multiple
      cancers, but not in the vast majority of normal cells. The enzyme is responsible
      for telomere protection and maintenance, and supports the proliferative
      immortality of cancer cells. Thus, it has been proposed that the specific
      inhibition of telomerase activity in tumors might have significant and beneficial
      therapeutic effects. To this goal we have designed, synthesized, and evaluated
      several oligonucleotide N3'-->P5' phosphoramidates as telomerase inhibitors.
      These oligonucleotides are complementary to the template region of the RNA domain
      of telomerase (hTR). The prepared compounds were evaluated in HME50-5E breast
      epithelial cells, where their effects on telomerase activity were determined
      using a cell-based telomerase (TRAP) assay at 24 as well as 72 h after exposure
      to compounds. The oligo-N3'-->P5' phosphoramidate inhibited telomerase activity
      in cells in the presence of the cellular up-take enhancer (FuGENE6) in a dose-
      and sequence-dependent manner, with IC(50) values of approximately 1 nM.
      Inhibition of telomerase activity by this compound without the lipid carrier was
      not efficient. However, the isosequential oligonucleotide N3'-->P5' thio
      phosphoramidate was able to inhibit telomerase activity with or without lipid
      carriers at nM, or low-microM concentrations, respectively. This inhibition of
      telomerase activity in HME50-5E cells by the oligonucleotide thio
      phosphoramidates was also sequence specific. Long-term treatment of the cells
      with 0.5 microM of FuGENE6 formulated 13-mer thio-phosphoramidates, fully
      complementary to hTR, resulted in gradual telomere shortening, followed by
      cellular senescence and apoptosis, as would be predicted for a telomerase
      inhibitor. The mismatched control compound had no effect on cell proliferation.
      The results suggest that the oligonucleotide N3'-->P5' phosphoramidates, and
      particularly thio-phosphoramidates, might be further developed as selective anti
      telomerase reagents.

PMID- 11850791
TI  - Clinical utility of telomerase in cancer.
AB  - This review will focus on the clinical utilities of telomerase for human cancer
      diagnosis. Much attention has been focused on detection of telomerase activity
      and its essential components (hTR and hTERT) in cancer and noncancerous tissues.
      Expression of hTR and hTERT is upregulated in almost all human malignant tumors
      but not in benign or normal tissues with the exception of germline cells,
      proliferative stem cells, activated lymphocytes, and certain benign tumors. Thus,
      telomerase is a useful marker for cancer diagnosis and in some instance as a
      prognostic indicator of outcome. Telomerase detection in cells derived from
      breast fine needle aspirates, bronchial washes, and pancreatic juices show high
      sensitivity and specificity for cancer detection. In tissue samples, the level of
      telomerase activity is a useful prognostic indicator in certain adult cancers
      such as gastric and colon cancers and in neuroblastomas. Immunohistochemical
      detection of hTERT will facilitate exact diagnosis of the telomerase positive
      cells and expand the application of telomerase in cancer diagnosis.

PMID- 11850792
TI  - Telomerase: its clinical relevance in the diagnosis of bladder cancer.
AB  - More than 50 years ago, Papanicolaou recognized the importance of a non-invasive
      technique for the diagnosis and follow-up of patients with carcinoma of the
      urinary bladder. Cystoscopy, however, has remained the 'gold standard' since no
      currently available non-invasive method can compete with cystoscopy's sensitivity
      and specificity. The detection of the ribonucleoprotein telomerase or the
      telomerase subunits human telomerase RNA (hTR) and human telomerase reverse
      transcriptase (hTERT) in urine samples offer new diagnostic perspectives. The
      present article presents a review of publications in the literature and evaluates
      their clinical relevance. The experimental studies reported to date are very
      promising and show that telomerase exactly fulfils the requirements for a good
      diagnostic marker for carcinoma of the urinary bladder. The diagnostic
      application remains in an experimental stage and telomerase is still several
      steps away for routine use as a clinical parameter. The remaining steps leading
      to its routine clinical application will be discussed.

PMID- 11850793
TI  - Telomerase as a therapeutic target for malignant gliomas.
AB  - Telomerase, a ribonucleoprotein enzyme, is considered as a potential target of
      cancer therapy because of its preferential expression in tumors. In particular,
      malignant gliomas are one of the best candidates for telomerase-targeted therapy.
      It is because malignant gliomas are predominantly telomerase-positive, while
      normal brain tissues do not express telomerase. In theory, there are two
      telomerase-associated therapeutic approaches for telomerase-positive tumors. One
      approach is the anti-telomerase cancer therapy to directly inhibit telomerase
      activity, resulting in apoptotic cell death or growth arrest. Two major
      components of the telomerase holoenzyme complex, the RNA template (hTER) and
      catalytic subunit (reverse transcriptase, hTERT) are well considered as
      therapeutic targets. The other approach is the telomerase-specific cancer therapy
      by targeting telomerase-expressing tumor cells as a means to directly kill the
      cells. Strategies using the transfer of therapeutic gene under the hTERT promoter
      system as well as immunotherapy directed against telomerase-positive cells are
      generally included. These telomerase-associated therapies are very promising for
      the treatment of malignant gliomas.

PMID- 11850794
TI  - Analysis of telomerase as a diagnostic biomarker of cervical dysplasia and
      carcinoma.
AB  - Telomerase expression is a potentially important marker of high-grade cervical
      dysplasia and squamous cell carcinoma (SCC). The routine practice of cervical
      cytology is limited by problems of false negative diagnoses as well as by poor
      specificity for clinically significant lesions in patients with low-grade
      cytologic abnormalities. Telomerase is widely expressed in most SCCs as well as
      in a high proportion of high-grade squamous intraepithelial lesions.
      Histochemical studies have confirmed that telomerase is expressed in the lower
      portions of normal or metaplastic squamous mucosa but that telomerase positive
      cells extend into the upper epithelial layers in cases of high-grade dysplasia.
      Since the cervical smear samples the uppermost cell layers of the cervical
      mucosa, but does not normally include cells derived from the lower layers of the
      squamous mucosa, the detection of telomerase in exfoliated cells of the cervical
      smear may have specificity for clinically significant lesions. The analysis of
      hTR, hTERT, and telomerase activity are complicated by a number of technical
      factors that may lead to either false negative or false positive test results.
      Thus, the practical application of telomerase analysis as a diagnostic adjunct
      for cervical cytopathology may depend on the development of more reliable and
      sensitive assay systems, possibly formatted for cytochemical applications.

PMID- 11850795
TI  - Telomerase as a universal tumor-associated antigen for cancer immunotherapy.
AB  - Although the search for pharmacologic inhibitors of telomerase activity
      represents a promising approach for telomerase-based anti-cancer therapy, the
      immunological properties of the telomerase reverse transcriptase hTERT suggest
      that the enzyme is also an attractive target for novel immunotherapies against
      cancer. Data from both human and murine systems demonstrate that cytotoxic T
      lymphocytes (CTL) can recognize peptides derived from TERT and kill TERT-positive
      tumor cells of multiple histologies. Given the vast overexpression of hTERT in
      human tumors and its low-level expression in rare normal tissues, clinical trials
      have begun that test the credentials of hTERT as a broadly applicable target for
      immunotherapy of cancer.

PMID- 11850796
TI  - Telomeres and telomerase in hematologic neoplasia.
AB  - Normal hematopoietic cells express telomerase activity, however the presence of
      telomerase does not necessarily imply stable and thus unchanging telomere length.
      Gradual telomere loss with aging and rapid cycling of hematopoietic stem cells
      might contribute to immunosenescence, exhausted hematopoiesis, and increased
      likelihood of malignant transformation. In leukemias and lymphomas, telomere
      length may reflect the cellular proliferative history, prior to immortalization.
      The level of telomerase activity is generally influenced by the fraction of cells
      in the proliferative pool. Shortened telomeres and high telomerase activity
      almost always correlates with disease severity in hematologic neoplasias such as
      relapsed leukemia and high-grade lymphomas, indicating that measurement of
      telomere length and telomerase activity might be useful to monitor disease
      condition. Since the mode of action of telomerase inhibitors may require
      telomeric shortening before induction of apoptosis, anti-telomerase therapy might
      be helpful for adjuvant therapy following conventional chemotherapy, in vitro
      purging of neoplastic cells in stem cell transplantation, and treating minimal
      residual disease. Some promising areas of tissue engineering include rejuvenation
      of hematopoietic stem cells for improving stem cell transplants or enhancing
      general immunity for older patients.

PMID- 11850797
TI  - Complex regulatory mechanisms of telomerase activity in normal and cancer cells:
      how can we apply them for cancer therapy?
AB  - Telomerase activation is observed in almost 90% of human cancers but not in
      normal tissues of somatic origin and thus is a critical step for multistep
      carcinogenesis. A more thorough understanding of telomerase regulation may
      provide not only a molecular basis of cancer progression but also as a way to
      manipulate telomerase activity as a potential therapeutic modality. Recent
      progress in studies on telomerase regulation has shown that telomerase activation
      is achieved at various steps, including transcriptional and post-transcriptional
      levels of the telomerase reverse transcriptase (hTERT) gene. Although a number of
      potentially important mechanisms of telomerase activation have been proposed,
      none of the current models can fully explain tumor-specific activation of
      telomerase, suggesting a need for further extensive analysis. This review
      includes a summary of recent works on telomerase regulation and a discussion of
      how we can overcome this situation.

PMID- 11850798
TI  - Concomitant activation of the PI3K-Akt and the Ras-ERK signaling pathways is
      essential for transformation by the V-SEA tyrosine kinase oncogene.
AB  - V-SEA is the transforming component of S13 Avian Erythroblastosis Retrovirus that
      causes erythroblastosis and anemia in chicken. Like all members in the family
      (MET, RON, SEA), its cytosolic domain possesses two tyrosine autophosphorylation
      sites in the tandemly arranged bidentate motif that serve as docking sites for
      SH2 domain-containing proteins. Here, we investigated phosphotyrosine-dependent
      activation of signaling pathways and their significance in V-SEA-induced
      transformation and/or proliferation. We demonstrated that V-SEA activates the
      PI3K-Akt signaling pathway primarily in Y557- and secondarily in Y564-dependent
      manner. V-SEA was also shown to induce the tyrosine phosphorylation of the Gab2
      protein, leading to PI3K association and thus providing an alternative route for
      PI3K activation. On the other hand, activation of the Ras-ERK pathway is
      primarily via Y564 and secondarily via Y557. A dominant-negative form of Ras
      inhibited V-SEA-induced ERK phosphorylation in concentration dependent manner
      suggesting the importance of the Grb2-Ras signaling axis in V-SEA-induced ERK
      activation. The biological significance of activation of the PI3K-Akt and the Ras
      ERK pathways in V-SEA-induced transformation was analysed in the V-SEA-RAT1 and V
      SEA-3T3 cell lines by employing specific inhibitors, LY294002 and PD98059
      compounds. Both the PD and LY compounds inhibited cell growth, but only the PD
      compound caused reversion of the transformed phenotype. In addition, both
      compounds inhibited focal colony formation by the transformants in soft agar.
      Thus, transformation by the V-SEA oncogene is a function of the concomitant
      activation of, at least, the PI3K-Akt and Ras-ERK signaling pathways that
      regulate cell growth and morphology.

PMID- 11850799
TI  - The cancer growth suppressing gene mda-7 induces apoptosis selectively in human
      melanoma cells.
AB  - Human melanoma cells growth arrest irreversibly, lose tumorigenic potential and
      terminally differentiate after treatment with a combination of fibroblast
      interferon (IFN-beta) and the protein kinase C activator mezerein (MEZ). Applying
      subtraction hybridization to this model differentiation system permitted cloning
      of melanoma differentiation associated gene-7, mda-7. Expression of mda-7
      inversely correlates with melanoma development and progression, with elevated
      expression in normal melanocytes and nevi and increasingly reduced expression in
      radial growth phase, vertical growth phase and metastatic melanoma. When
      expressed by means of a replication incompetent adenovirus (Ad.mda-7) growth of
      melanoma, but not normal early passage or immortal human melanocytes, is
      dramatically suppressed and cells undergo programmed cell death (apoptosis).
      Infection of metastatic melanoma cells with Ad.mda-7 results in an increase in
      cells in the G(2)/M phase of the cell cycle and changes in the ratio of pro
      apoptotic (BAX, BAK) to anti-apoptotic (BCL-2, BCL-XL) proteins. Ad.mda-7
      infection results in a temporal increase in mda-7 mRNA and intracellular MDA-7
      protein in most of the melanocyte/melanoma cell lines and secretion of MDA-7
      protein is readily detected following Ad.mda-7 infection of both melanocytes and
      melanoma cells. The present studies document a differential response of
      melanocytes versus melanoma cells to ectopic expression of mda-7 and support
      future applications of mda-7 for the gene-based therapy of metastatic melanoma.

PMID- 11850800
TI  - Downregulation of c-fos gene transcription in cells transformed by E1A and cHa
      ras oncogenes: a role of sustained activation of MAP/ERK kinase cascade and of
      inactive chromatin structure at c-fos promoter.
AB  - REF cells transformed by oncogenes E1A and cHa-ras reveal high and constitutive
      DNA-binding activity of AP-1 factor lacking in c-Fos protein. Consistently, the
      transcription of c-fos gene has been found to be downregulated. To elucidate the
      mechanisms of c-fos downregulation in E1A+cHa-ras transformants, we studied the
      levels of activity of ERK, JNK/SAPK and p38 kinases and phosphorylation state of
      Elk-1 transcription factor involved in regulation of c-fos gene. Using two
      approaches, Western blot analysis with phospho-specific antibodies to MAP kinases
      and in vitro kinase assay with specific substrates, we show here that ectopic
      expression of E1A and ras oncogenes leads to a sustained activation of ERK and
      p38 kinases, whereas JNK/SAPK kinase activity is similar to that in non
      transformed REF52 cells. Due to sustained activity of the MAP kinase cascades,
      Elk-1 transcription factor is being phosphorylated even in serum-starved E1A+cHa
      ras cells; moreover, serum does not additionally increase phosphorylation of Elk
      1, which is predominant TCF protein bound to SRE region of c-fos gene promoter in
      these cells. Although the amount of ternary complexes SRE/SRF/TCF estimated by
      EMSA was similar both in serum-starved and serum-stimulated transformed cells,
      serum addition still caused a modest activation of c-fos gene transcription at
      the level of 20% to normal REF cells. In attempt to determine how serum caused
      the stimulatory effect, we found that PD98059, an inhibitor of MEK/ERK kinase
      cascade, completely suppressed serum-induced c-fos transcription both in REF and
      E1A+cHa-ras cells, implicating the ERK as primary kinase for c-fos transcription
      in these cells. In contrast, SB203580, an inhibitor of p38 kinase, augmented
      noticeably serum-stimulated transcription of c-fos gene in REF cells, implying
      the involvement of p38 kinase in negative regulation of c-fos. Furthermore,
      sodium butyrate, an inhibitor of histone deacetylase activity, was capable of
      activating c-fos transcription both in serum-stimulated and even in serum-starved
      E1A+cHa-ras cells. Conversely, serum-starved REF cells fail to respond to sodium
      butyrate treatment by c-fos activation confirming necessity of prior Elk-1
      phosphorylation. Taken together, these data suggest that downregulation of c-fos
      in E1A+cHa-ras cells seems to occur due to a maintenance of a refractory state
      that arises in normal REF cells after serum-stimulation. The refractory state of
      c-fos in E1A+cHa-ras cells is likely a consequence of Ras-induced sustained
      activation of MAPK (ERK) cascade and persistent phosphorylation of TCF (Elk-1)
      bound to SRE. Combination of these events eventually does contribute to formation
      of an inactive chromatin structure at c-fos promoter mediated through recruitment
      of histone deacetylase activity.

PMID- 11850801
TI  - Implication of p53 in base excision DNA repair: in vivo evidence.
AB  - The tumor suppressor p53 plays an important role in response to DNA damage,
      including DNA repair. One DNA repair pathway, nucleotide excision repair (NER),
      has been well-documented to be regulated by p53. It seemed probable that p53 may
      affect other DNA repair pathways. We employed matched isogenic pairs of cell
      lines, wild-type or p53-deficient, to investigate this question using methyl
      methanesulfonate (MMS), a base-damaging agent. Alkylation damage induced by MMS
      is repaired exclusively by the base excision repair (BER) pathway. Cells carrying
      mutant or no p53 genes exhibited slow BER of MMS-induced DNA damage, and
      exhibited MMS-sensitivity. One contributing factor is the abundance of DNA
      polymerase beta (beta-pol), an enzyme required for BER, which was almost absent
      in p53 mutant and p53-null cells. Our findings demonstrate an in vivo requirement
      for p53 in regulating the base excision repair response, a novel finding of great
      potential importance in understanding the DNA repair branch of the p53 pathway.

PMID- 11850802
TI  - The human involucrin gene contains spatially distinct regulatory elements that
      regulate expression during early versus late epidermal differentiation.
AB  - Human involucrin (hINV) is a keratinocyte protein that is expressed in the
      suprabasal compartment of the epidermis and other stratifying surface epithelia.
      Involucrin gene expression is initiated early in the differentiation process and
      is maintained until terminal cell death. The distal regulatory region (DRR) is a
      segment of the hINV promoter (nucleotides -2473/-1953) that accurately
      recapitulates the normal pattern of suprabasal (spinous and granular layer)
      expression in transgenic mouse epithelia. To identify sequences that mediate
      expression at specific stages of differentiation, we divided the DRR into two
      segments, a 376 nucleotide upstream region (DRR(-2473/-2100)) and a 147
      nucleotide downstream region (DRR(-2100/-1953)), and evaluated the ability of
      these sequences to drive expression in transgenic mice. The DRR(-2473/-2100)
      segment drives expression at a level comparable to that observed for the DRR, but
      expression is restricted to the upper granular layers (i.e., no spinous layer
      expression). In contrast, the DRR(-2100/-1953) segment does not drive expression.
      However, reassembling the DRR restores the complete range of expression. These
      results suggest that two distinct, spatially-separate elements are required to
      specify the complete differentiation-dependent program of involucrin gene
      expression. To identify specific transcription factor binding sites involved in
      this regulation, we mutated an activator protein-1 binding site, AP1-5, located
      within DRR(-2473/-2100) segment. This site binds AP1 transcription factors
      present in mouse epidermal extracts, and its mutation eliminates appropriate hINV
      expression. This result suggests that AP1 factors participate as components of a
      multi-component transcription factor complex that is required for regulation.

PMID- 11850803
TI  - Regulation of the mitochondrial checkpoint in p53-mediated apoptosis confers
      resistance to cell death.
AB  - The p53 tumor suppressor protein inhibits tumor formation, in part by inducing
      apoptosis, which is inhibited by anti-apoptotic Bcl-2 family members Bcl-2 and
      adenovirus E1B 19K. We have identified p53-apoptotic signaling events which are
      targeted for inhibition by E1B 19K. Apoptotic signaling by p53 induced a Bid
      independent conformational change in Bax, a Bax-Bak interaction, release of
      cytochrome c and Smac/DIABLO from mitochondria, caspase-9 and -3 activation,
      cleavage of known caspase substrates, and apoptosis. When p53-dependent apoptosis
      was blocked by E1B 19K expression, E1B 19K bound Bak, and the Bax-Bak interaction
      was inhibited. Cytochrome c and Smac/DIABLO release from mitochondria was also
      inhibited in E1B 19K expressing cells and cells remained viable. After a
      prolonged p53 death stimulus, the inhibition of the mitochondrial death
      checkpoint by E1B 19K failed, and cytochrome c and Smac/DIABLO were released from
      mitochondria, and became degraded. Despite this eventual failure to inhibit the
      mitochondrial checkpoint, caspase-9 and -3 were not activated, and cells remained
      viable even upon treatment with an exogenous death stimulus. Thus, p53 induces
      apoptosis in part through Bax and Bak, and even an incomplete inhibition of this
      mitochondrial checkpoint may be sufficient to confer resistance to cell death.

PMID- 11850804
TI  - Estrogen-like effects of thyroid hormone on the regulation of tumor suppressor
      proteins, p53 and retinoblastoma, in breast cancer cells.
AB  - T47D cells represent an estrogen-responsive human ductal carcinoma cell line
      which expresses detectable levels of estrogen receptor (ER). We have previously
      shown that estradiol (E(2)) treatment of T47D cells causes an increase in the
      level of p53 and a concomitant phosphorylation of retinoblastoma protein (pRb).
      In the present study, we have analysed the expression of p53 and phosphorylation
      state of pRb and compared the effects of E(2) and triiodothyronine (T(3)) on
      these phenomena. Cells were grown in a medium containing charcoal-treated serum
      to deplete the levels of endogenous steroids. Upon confluency, the cells were
      treated with T(3) (10(-12) to 10(-7) M) for 24 h and the presence of p53 and pRb
      was detected by Western analysis. E(2) treatment of cells caused a 2-3-fold
      increase in the level of p53. Presence of T(3) in the medium caused a gradual
      increase in the level of p53 in a concentration-dependent manner. Under the above
      conditions, pRb was phosphorylated (detected as an upshift during SDS-PAGE) in
      the presence of E(2) and T(3). Supplementation of growth medium with T(3) (1
      microM) caused an increase in the rate of proliferation of T47D cells and induced
      hyperphosphorylation of pRb within 4 h; this effect was maintained for up to 12
      h. When ICI 164 384 (ICI) (1 microM), an ER antagonist, was combined with E(2) (1
      nM) or T(3) (1 microM), effects of hormones on cell proliferation and
      hyperphosphorylation of pRb were blocked. Western analysis of p53 was
      supplemented with its cytolocalization by immuno-labeling using laser scanning
      confocal fluorescence microscopy, which revealed an ICI-sensitive increase in the
      abundance of p53 in hormone-treated cells. Steroid binding analysis revealed lack
      of competition by T(3) for the [(3)H]E(2) binding. These results indicate that
      T(3) regulates T47D cell cycle progression and proliferation raising the p53
      level and causing hyperphosphorylation of pRb by a common mechanism involving ER
      and T(3) receptor (T(3)R)-mediated pathways.

PMID- 11850805
TI  - The human telomerase gene: complete genomic sequence and analysis of tandem
      repeat polymorphisms in intronic regions.
AB  - In this work, the full-length hTERT gene was isolated and the sequence of the
      previously unknown region in intron 6 as well as that of upstream and downstream
      hTERT regions was determined. We have shown that intron 6 includes a variable
      number of tandem repeats (VNTR) of a 38 bp sequence, (hTERT-VNTR 6-1). Eight
      alleles of hTERT-VNTR 6-1 were identified among 103 unrelated individuals,
      ranging from 27 to 47 repeats. hTERT-VNTR 2-2 is another new 61 bp minisatellite
      repeat found in intron 2 of hTERT. At least four alleles of hTERT-VNTR 2-2 can be
      distinguished. Previous studies have described polymorphisms for minisatellites
      hTERT-VNTR 2-1, a 42 bp repeat in intron 2, and hTERT-VNTR 6-2, a 36 bp repeat in
      intron 6. These, together with another minisatellite found in intron 12, add up
      to five such structures within the hTERT gene. The segregation of hTERT
      minisatellites was analysed in families, revealing that the VNTRs are transmitted
      through meiosis following a Mendelian inheritance. Minisatellites in hTERT were
      also analysed in matching normal and cancer tissues from patients with tumors; in
      one patient with a kidney tumor, the two VNTRs in intron 6 had undergone
      concomitant rearrangements. This observation suggests that chromosomal
      rearrangements implicating these VNTRs may be associated with the activation of
      telomerase expression in cancer cells.

PMID- 11850806
TI  - Role of cAMP, PKA and Rap1A in thyroid follicular cell survival.
AB  - Cyclic AMP (cAMP) rescues cells from apoptosis stimulated by diverse insults. We
      examined the role of cAMP as a survival factor, and the signaling pathways
      through which cAMP affords protection. Rat thyroid cells were selected for these
      studies given the predominant role of cAMP in thyrotropin (TSH)-stimulated
      proliferation and as an oncogene in thyroid cells. Wistar rat thyroid (WRT) cells
      perished via apoptosis following sodium nitroprusside (SNP) treatment. Elevations
      in cAMP following treatment with forskolin, 8BrcAMP or IBMX rescued cells from
      SNP-induced cell death. Notably, TSH prevented apoptosis, implicating an
      important role for this hormone as a survival factor. Cyclic AMP activates
      multiple signaling pathways including those mediated through PKA, PI3K, p70S6k
      and the Ras-related small G protein, Rap1. Intriguingly, multiple pathways
      modulate thyroid cell survival. Interference with cAMP-stimulated p70S6k, but not
      PI3K, activity abrogated cell survival. Treatment with PKA inhibitors was
      sufficient to stimulate apoptosis in hormone-deprived cells and markedly enhanced
      cell death in response to SNP. Cells expressing an activated Rap1A mutant
      exhibited an enhanced sensitivity to SNP-induced apoptosis, while those
      expressing dominant negative Rap1A were resistant to SNP-initiated cell death.
      Together, these findings establish an important role for PKA and Rap1 in the
      control of thyroid cell survival.

PMID- 11850807
TI  - Correlation of postoperative recurrence in hepatocellular carcinoma with
      demethylation of repetitive sequences.
AB  - Restriction landmark genomic scanning (RLGS) was utilized to identify novel
      genomic alterations in hepatocellular carcinoma (HCC). Thirty-one HCC samples
      were examined by RLGS. Two high intensity spots were common to several RLGS
      profiles of different HCCs. Nucleotide sequencing and homology search analysis
      showed that these spots represented repetitive sequences, Human tandem repeat
      sequence (Genbank, L09552) and centromeric NotI cluster (Genbank, Y10752). These
      intensified signals were attributable to the occurrence of demethylated areas in
      the recognition sequence of the NotI site of the corresponding fragments. The
      intensity of these spots in the RLGS profile reflects their degree of
      demethylation, which was significantly correlated with postoperative recurrence,
      even in patients regarded as belonging to the good prognosis group by
      conventional prognostic factors. Multivariate analysis showed that the
      intensities of the two spots retained independent prognostic value. This is a new
      type of predictive factor for HCC based on epigenetic changes in
      hepatocarcinogenesis, and in the future it is expected to be of great value in
      making preoperative diagnosis and selecting postoperative therapy.

PMID- 11850808
TI  - HOXD3 enhances motility and invasiveness through the TGF-beta-dependent and 
      independent pathways in A549 cells.
AB  - Homeobox genes regulate sets of genes that determine cellular fates in embryonic
      morphogenesis and maintenance of adult tissue architecture by regulating cellular
      motility and cell-cell interactions. Our previous studies showed that a specific
      member, HOXD3, when overexpressed, upregulates integrin beta3 expression in human
      erythroleukemia HEL cells and lung cancer A549 cells, and enhances their motility
      and invasiveness. We performed a microarray study of over 7075 genes to determine
      the mechanisms underlying the HOXD3-enhanced motility and invasiveness in A549
      cells. RT-PCR-based tracking gene analyses highlighted a set of TGF-beta
      upregulated genes, which included matrix metalloproteinase-2, syndecan-1, CD44,
      and TGF-beta-induced 68 kDa protein. Exogenous TGF-beta also caused this pattern
      of upregulation in A549 cells and enhanced their migratory and invasive activity,
      confirming the involvement of TGF-beta signaling. However, HOXD3 reduced the
      expression of TGF-beta-independent genes coding for desmosomal components such as
      desmoglein, desmoplakin and plakoglobin which are known to suppress tumor
      invasion and metastasis. These results suggest that HOXD3 enhances the invasive
      and metastatic potential of cancer cells through the TGF-beta-dependent and 
      independent pathways.

PMID- 11850809
TI  - Basic fibroblast growth factor (bFGF)-induced cell death is mediated through a
      caspase-dependent and p53-independent cell death receptor pathway.
AB  - The mechanism of bFGF-induced cell death in tumours of the Ewing's sarcoma family
      (ESFT) has been investigated. bFGF-induces phosphorylation of FGFr 1 and
      activation of Ras/ERK in ESFT cells that die when exposed to bFGF. Induction of
      cell death was associated with activation of both initiator (caspases-2, -8 and 
      10) and effector (caspases-3, -6 and -7) caspases. Moreover, the general caspase
      inhibitor Z-VAD-FMK protected cells from bFGF-induced cell death. After treatment
      with bFGF, a loss of mitochondrial transmembrane potential was accompanied by
      down-regulation of Bcl-2. However, the observed cell death was not associated
      with release of cytochrome c from the mitochondria. Furthermore, expression of
      wild-type p53 was not required for bFGF-induced cell death. These observations
      suggest that bFGF-induced cell death may be mediated through a cell death
      receptor mechanism, supported by up-regulation of the p75 neurotrophin receptor.
      bFGF-induced cell death was associated with up-regulation of p21 and p53, down
      regulation of PCNA and cyclin A and a decrease in active pRb1, changes consistent
      with accumulation of cells in G1. These data demonstrate that bFGF-induced cell
      death is effected through a caspase-dependent and p53-independent mechanism, that
      may be mediated through a cell death receptor pathway.

PMID- 11850810
TI  - Hypothesis: a novel route for immortalization of epithelial cells by Epstein-Barr
      virus.
AB  - Transfection of primate tissue explants with a specific sub-fragment (p31) of EBV
      DNA results in epithelial (but no other) cells proliferating indefinitely
      (becoming 'immortalized') without evidence of a 'growth crisis'. Molecular
      evidence supports integration of viral information into the host chromosome, and
      an early genotypic alteration involving specific amplification of a sub-component
      (IR1) of p31 DNA, followed by apparent loss of viral DNA from chromosomes,
      consistent with a 'hit and run' mechanism. However, analysis at the individual
      cell level during long-term culture, by FISH techniques, reveals chromosomal
      alterations, and viral sequences surviving within double minute (DM) bodies.
      Changing growth patterns occurring at different stages during propagation (>a
      year in culture) may be explained by sporadic reintegration of surviving viral
      DNA into the host chromosome. Notably, throughout culture, telomere lengths in
      chromosomal DNAs do not alter but rather retain the length observed in the
      primary cell populations. Introduction of a growth stimulating function of EBV,
      BARF1, into the immortalized, non-clonable epithelial cells under conditions
      which permit overexpression, allows clonal populations to be derived. Based on
      the data, mechanisms of immortalization, in the absence of a proven viral
      oncogene in p31 DNA, and possible genes involved, are considered.

PMID- 11850811
TI  - Novel estrogen and tamoxifen induced genes identified by SAGE (Serial Analysis of
      Gene Expression).
AB  - The breast cancer promoting effects of estrogen and the chemopreventive effects
      of tamoxifen are thought to be mediated by the estrogen receptor, a ligand
      dependent transcription factor. Therefore, comprehensive analysis of gene
      expression profiles following estrogen or tamoxifen treatment may help us better
      understand the role estrogen plays in tumorigenesis. We utilized SAGE (Serial
      Analysis of Gene Expression) technology to identify genes regulated by estrogen
      and tamoxifen in the ZR75-1 estrogen dependent breast cancer cell line. In this
      manner we have identified several genes that were regulated by estrogen or
      tamoxifen. Here we report the identification and initial characterization of EIT
      6 (Estrogen Induced Tag-6), a novel nuclear protein and a new member of the
      evolutionarily conserved SM-20 family of growth regulatory immediate-early genes.
      EIT-6 appears to be a direct transcriptional target of the estrogen receptor and
      constitutive expression of EIT-6 promotes colony growth in human breast cancer
      cells. These data indicate that EIT-6 may play a role in estrogen induced cell
      growth.

PMID- 11850812
TI  - Inhibition of human endothelial cell proliferation by ShIF, a vacuolar H(+)
      ATPase-like protein.
AB  - ShIF is a bone marrow stroma cell-derived factor originally identified to support
      proliferation of bone marrow cells in vitro. This protein shares high sequence
      homology to the yeast vacuolar H(+)-ATPase subunit, Vph1p, and the 116 kDa proton
      pump of the rat and bovine synaptic vesicle, Vpp1. We examined the function of
      ShIF in the proliferation of human umbilical vein endothelial cells (HUVEC). ShIF
      inhibited HUVEC proliferation in a dose-dependent manner. Recombinant ShIF added
      at 10 and 20 ng/ml inhibited HUVEC proliferation by 21.6 and 44.3%, respectively
      and increasing the concentration of ShIF to 100 ng/ml inhibited proliferation by
      as much as 55.5%. When HUVEC cells were cultured at various concentrations of
      ShIF in the presence of anti-ShIF antibody, the inhibitory effects of ShIF to
      HUVEC proliferation were abrogated by 89-91% indicating that the activity of ShIF
      to HUVEC was specific. HUVEC cultured in the presence of ShIF and bafilomycin, a
      specific inhibitor of ATPase, resulted to a 90% growth inhibition. Thus, ShIF may
      act as an antagonist to the ATPase complex by disrupting the production of
      cellular ATP thereby decreasing the ability of HUVEC to proliferate.

PMID- 11850813
TI  - ATM-dependent activation of the gene encoding MAP kinase phosphatase 5 by
      radiomimetic DNA damage.
AB  - Cellular responses to DNA damage are mediated by an extensive network of
      signaling pathways. The ATM protein kinase is a master regulator of the response
      to double-strand breaks (DSBs), the most cytotoxic DNA lesion caused by ionizing
      radiation. ATM is the protein missing or inactive in patients with the
      pleiotropic genetic disorder ataxia-telangiectasia (A-T). A major response to DNA
      damage is altered expression of numerous genes. While studying gene expression in
      control and A-T cells following treatment with the radiomimetic chemical
      neocarzinostatin (NCS), we identified an expressed sequence tag that represented
      a gene that was induced by DSBs in an ATM-dependent manner. The corresponding
      cDNA encoded a dual specificity phosphatase of the MAP kinase phosphatase family,
      MKP-5. MKP-5 dephosphorylates and inactivates the stress-activated MAP kinases
      JNK and p38. The phosphorylation-dephosphorylation cycle of JNK and p38 by NCS
      was attenuated in A-T cells. Thus, ATM modulates this cycle in response to DSBs.
      These results further highlight ATM as a link between the DNA damage response and
      major signaling pathways involved in proliferative and apoptotic processes.

PMID- 11850814
TI  - Inhibition of HOS expression and activities by Wnt pathway.
AB  - BetaTrCP and HOS are closely related F-box proteins, which play key roles in
      ubiquitination and degradation of beta-catenin and IkappaB through associating
      with those phosphorylated substrates and recruiting SCF E3 ubiquitin ligase. Here
      we report that activation of Wnt/beta-catenin signal transduction pathway
      elevates betaTrCP levels but inhibits expression of HOS in 293T cells. Similar
      disparity is likely to exist in human colorectal tumors. In the NIH3T3 cells,
      which express HOS, but not betaTrCP, Wnt/beta-catenin signaling leads to
      inhibition of HOS promoter activity and NF-kappaB-driven transcription as well as
      to stabilization of beta-catenin. These results indicate that expression and
      activities of HOS are negatively regulated by Wnt/beta-catenin pathway.

PMID- 11850816
TI  - A conserved intronic response element mediates direct p53-dependent
      transcriptional activation of both the human and murine bax genes.
AB  - Both the human and the mouse bax promoters contain p53 binding sites which are
      sufficient to confer p53-dependent transcriptional activation in a heterologous
      setting. Nevertheless in the context of the bax promoter, these sites do not
      mediate a p53-dependent response, suggesting that bax may not be a direct
      transcriptional target of p53. Here, data are presented identifying a conserved
      p53 response element in the first intron of both the human and the murine bax
      genes. This element both in isolation and in the context of the first intron
      conferred p53-dependent transcriptional activation upon a minimal promoter.
      Electrophoretic mobility shift assays demonstrated that this sequence also is
      capable of mediating sequence specific binding to p53. p53 effectively activated
      transcription through both human and murine bax gene reporter constructs, whereas
      deletion of the intronic response element abrogated the p53-responsiveness of
      both reporters. Interestingly, tumor-derived mutants of p53 which are defective
      in inducing an apoptotic response retain the ability to activate transcription
      via the bax intronic p53 site. Since these mutants are transcriptionally inactive
      on the p53 site in the bax promoter, the ability of these mutants to up
      regulating endogenous bax mRNA levels supports a role for the intronic element in
      p53-dependent up-regulation of bax expression. Taken together, these results show
      the requirement for a novel intronic element in the p53-dependent transcriptional
      activation of bax, and demonstrate that bax is indeed a direct and evolutionarily
      conserved transcriptional target of p53.

PMID- 11850815
TI  - Differential protein expression, DNA binding and interaction with SV40 large
      tumour antigen implicate the p63-family of proteins in replicative senescence.
AB  - P53 activity plays a key role in mammalian cells when they undergo replicative
      senescence at their Hayflick limit. To determine whether p63 proteins, members of
      the family of p53-related genes, are also involved in this process, we examined
      their expression in serially passaged rat embryo fibroblasts. Upon senescence,
      two truncated DeltaNp63 proteins decreased in abundance whereas two TAp63
      isoforms accumulated. 2-D gel analysis showed that the DeltaNp63 proteins
      underwent post-translational modifications in both proliferating and senescent
      cells. Direct binding of DeltaNp63 proteins to a p53 consensus motif was greater
      in proliferating cells than senescent cells. In contrast p63alpha isoforms bound
      to DNA in a p53 dependent manner and this was higher in senescent cells than
      proliferating cells. An interaction of p63alpha proteins with SV40 large tumour
      antigen was also detected and ectopic expression of DeltaNp63alpha can extend the
      lifespan of rat embryo fibroblasts. Taken together the results indicate that p63
      proteins may play a role in replicative senescence either by competition for p53
      DNA binding sites or by direct interaction with p53 protein bound to DNA.

PMID- 11850817
TI  - Hepatocyte growth factor/scatter factor activates proliferation in melanoma cells
      through p38 MAPK, ATF-2 and cyclin D1.
AB  - Members of the mitogen-activated protein kinase (MAPK) superfamily, including p38
      kinase and SAPK/JNK, play a central role in mediating cellular response to
      environmental stress, growth factors and cytokines. Hepatocyte growth
      factor/scatter factor (HGF/SF) is a multifunctional cytokine capable of eliciting
      mitogenic, motogenic and morphogenetic activities in responsive cells, and has
      been implicated in tumor development and metastasis. Binding of HGF/SF to its
      tyrosine kinase receptor c-Met stimulates multiple signal transduction pathways,
      leading to the activation of numerous transcription factors. We here report that
      HGF/SF can induce cyclin D1 expression in mouse melanoma cells, and that this up
      regulation is mediated in part by the activating transcription factor-2 (ATF-2).
      HGF/SF-mediated phosphorylation of ATF-2 was reduced in the presence of either
      the p38 kinase-specific inhibitor SB203580, a dominant negative p38 mutant, the
      SAPK/JNK inhibitor JNK-interacting protein-1 (JIP-1), or the phosphatidylinositol
      3-kinase (PI3K)-specific inhibitor LY294002. Activation of p38 kinase by HGF/SF
      was partially blocked by the PI3K-specific inhibitor as well. The upstream
      kinases for p38, MKK3/6, did not become activated following HGF/SF exposure, and
      ATF-2 activation was undiminished by transient transfection of a dominant
      negative MKK6 mutant. However, transcriptional up-regulation of cyclin D1 by
      HGF/SF was partially inhibited by the p38 kinase-specific inhibitor, and cyclin
      D1 protein induction was partially blocked by a dominant negative ATF-2 mutant.
      Notably, the p38 kinase-specific inhibitor was able to block melanoma cell
      proliferation but not motility. We conclude that the ATF-2 transcription factor
      becomes activated by HGF/SF through p38 MAPK and SAPK/JNK. Moreover, the p38-ATF
      2 pathway can help mediate proliferation signals in tumor cells through
      transcriptional activation of key cell cycle regulators.

PMID- 11850818
TI  - Expression of the PAX2 oncogene in human breast cancer and its role in
      progesterone-dependent mammary growth.
AB  - In this study, we first describe expression of the paired domain transcription
      factor PAX2 in the normal and cancerous human breast, then demonstrate in a
      murine model a novel function for PAX2 in the regulation of progesterone
      stimulation of secondary ductal growth. In human mammary tissue, PAX2 expression
      was coincident with sub-populations of mammary ductal cells, some of which
      possessed an undifferentiated histiotype, and was also found in >50% of the human
      breast tumors surveyed (n=38). In the mouse, mammary parenchyma with a targeted
      deletion of PAX2 developed normal ductal systems when grafted into wild-type host
      mammary fat pads, but failed to undergo higher order side-branching and lobular
      development in response to progesterone. A previously unsuspected PAX2/WT1
      (Wilms' tumor suppressor gene) regulatory axis in the mammary gland was also
      indicated. Using RT-PCR, a significant reduction in WT1 mRNA expression was
      detected in the PAX2 mutant glands compared to wild-type counterparts and double
      antibody immunohistochemistry detected the co-localization of PAX2 and WT1 in the
      nuclei of normal and cancerous breast cells. These data indicate a role for PAX2
      (and possibly WT1) in the regulation of the progesterone response of the mature
      mammary gland. The potential contribution of PAX2 to breast tumor pathogenesis is
      discussed.

PMID- 11850819
TI  - C-Jun N-terminal kinase is required for phorbol ester- and thapsigargin-induced
      apoptosis in the androgen responsive prostate cancer cell line LNCaP.
AB  - In early, androgen dependent stages of prostate cancer, androgen withdrawal, the
      major course of therapy in prostate cancer, leads to a rapid regression of the
      tumor as a result of apoptosis. However, prostate cancer invariably progresses to
      an androgen independent and apoptosis resistant stage for which no curative
      treatment is available. The molecular details of regression upon androgen
      withdrawal and progression to a resistant state are largely unknown. Here we show
      that c-Jun N-terminal Kinase (JNK) is activated strongly and in a sustained
      fashion by 12-O-tetradecanoylphorbol 13-acetate (TPA) and thapsigargin (TG), two
      agents which were previously shown to lead to apoptosis in the androgen
      responsive prostate cancer cell line LNCaP. The time course of JNK induction by
      both compounds correlated very well with the onset and progression of apoptosis
      in LNCaP cells. Inhibition of either ERK or p38 pathways did not affect TPA
      induced cell death. In the androgen-independent prostate cancer cell lines DU-145
      and PC-3, and in the cervical carcinoma cell line HeLaS3, TPA did not lead to
      apoptosis and there were no significant changes in JNK activity upon TPA
      treatment. The failure of TPA to induce JNK activity in PC-3, DU-145, and HelaS3
      cells was not due to a general defect in JNK signaling since ultraviolet (UV)
      irradiation dramatically increased JNK activity in all four cell lines. Specific
      inhibition of JNK by expression of the JNK Inhibitory Protein (JIP) dramatically
      inhibited both TPA- and TG-induced apoptosis. Furthermore, apoptosis induced by
      both agents was completely blocked by ectopic expression of the baculovirus
      caspase-inhibitor P35. Surprisingly, ZVAD-fmk, a cell-permeable
      fluoromethylketone inhibitor of caspases, had no effect on TPA-induced apoptosis,
      whereas it completely inhibited TG-induced cell death; JNK activity was not
      affected in either case. This indicates that ZVAD-fmk does not inhibit some of
      the caspases involved in TPA-induced apoptosis, and that despite the common
      requirement of JNK activation, TPA- and TG-induced cell death are mechanistically
      different. Furthermore, it also suggests that JNK is either upstream or
      independent of caspases in LNCaP cells. Collectively, these results indicate that
      apoptosis in LNCaP cells requires a sustained increase in JNK activity and
      caspase activation; components of these signaling pathways may be defective in
      the androgen independent prostate cancer cell lines.

PMID- 11850820
TI  - Inhibition of crystallin expression and induction of apoptosis by lens-specific
      E1A expression in transgenic mice.
AB  - Previous studies have shown that the adenovirus E1A oncoprotein can bind to and
      inactivate the retinoblastoma tumor suppressor protein (pRb) and the
      transcriptional coactivators CBP/p300. In this study, wild-type E1A12S or two
      deletion mutants (delN, which binds pRb but not CBP/p300; delCR2, which binds to
      CBP/p300 but not pRb) were linked to the lens-specific alphaA-crystallin
      promoter, and used to generate transgenic mice. Lens fiber cells expressing
      E1A12S or delCR2, both of which bind to CBP/p300, failed to upregulate beta
      crystallin and gamma-crystallin expression. In contrast, lens fiber cells
      expressing delN showed significant expression of beta- and gamma-crystallins.
      Lens fiber cells expressing delN showed cell cycle entry, marked apoptosis, and
      evidence for p53 activation, while cells expressing either 12S or delCR2 showed
      limited apoptosis and no evidence for upregulation of the p53-inducible gene p21.
      Our results suggest that the transcriptional coactivators CBP and/or p300 are
      required for the dramatic increases in crystallin expression that accompany
      terminal differentiation in the lens, and also for activation of p53 in response
      to inactivation of pRb in the lens.

PMID- 11850821
TI  - Anaplastic lymphoma kinase (ALK) activates Stat3 and protects hematopoietic cells
      from cell death.
AB  - The anaplastic lymphoma kinase (ALK) gene is characteristically translocated in
      Anaplastic Large Cell Lymphomas (ALCL) and the juxtaposition of the ALK gene to
      multiple partners results in its constitutive protein tyrosine kinase activity.
      We show here that expression of activated ALK induces the constitutive
      phosphorylation of Stat3 in transfected cells as well as in primary human ALCLs.
      Furthermore, immunohistochemical studies demonstrate that among distinct human B
      and T cell lymphomas, activation of Stat3 nuclear translocation is uniquely
      associated with ALK expression. NPM-ALK also binds and activates Jak3; however,
      Jak3 is not required for Stat3 activation or for cell transformation in vitro.
      Moreover, src family kinases are not necessary for NPM-ALK-mediated Stat3
      activation or transformation, suggesting that Stat3 may be phosphorylated
      directly by ALK. To evaluate relevant targets of ALK-activated Stat3, we
      investigated the regulation of the anti-apoptotic protein Bcl-x(L) and its role
      in cell survival in NPM-ALK positive cells. NPM-ALK expression caused enhanced
      Bcl-x(L) transcription, largely mediated by Stat3. Increased expression of Bcl
      x(L) provided sufficient anti-apoptotic signals to protect cells from treatment
      with specific inhibitors of the Jaks/Stat pathway or the Brc-Abl kinase. These
      studies support a pathogenic mechanism whereby stimulation of anti-apoptotic
      signals through activation of Stat3 contributes to the successful outgrowth of
      ALK positive tumor cells.

PMID- 11850822
TI  - Hypermethylation trigger of the glutathione-S-transferase gene (GSTP1) in
      prostate cancer cells.
AB  - Understanding what triggers hypermethylation of tumour suppressor genes in cancer
      cells is critical if we are to discern the role of methylation in the oncogenic
      process. CpG sites in CpG island promoters, that span most tumour suppressor
      genes, remain unmethylated in the normal cell, despite the fact that CpG sites
      are the prime target for de novo methylation by the DNA methyltransferases. The
      CpG island-associated with the GSTP1 gene is an intriguing example of a CpG rich
      region which is susceptible to hypermethylation in the majority of prostate
      tumours and yet is unmethylated in the normal prostate cell. In this study we
      evaluate a number of factors purported to be involved in hypermethylation to test
      their role in triggering hypermethylation of GSTP1 in prostate cancer DU145 and
      LNCaP cells. We find that hypermethylation is not associated with (1) elevated
      expression of the DNA methyltranferases, or (2) removal of Sp1 transcription
      factor binding sites in the CpG island or (3) removal of CpG island boundary
      elements or (4) prior gene silencing. Instead our results support a model that
      requires a combination of prior gene silencing and random "seeds" of methylation
      to trigger hypermethylation of the GSTP1 gene in the prostate cancer cell. We
      propose that the GSTP1 gene is initially silenced in the prostate cancer and
      random sites of methylation accumulate that result in subsequent hypermethylation
      and chromatin remodelling.

PMID- 11850823
TI  - TC21 mediates transformation and cell survival via activation of
      phosphatidylinositol 3-kinase/Akt and NF-kappaB signaling pathway.
AB  - The signaling pathways of TC21-mediated transformation and cell survival are not
      well-established. In this study, we have investigated the role of PI3-K/Akt
      signaling pathway in oncogenic-TC21-mediated transformation and cell survival. We
      found that oncogenic-TC21 stimulated the PI3-K activity. This was associated with
      the activation of Akt, a key component of PI3-K signaling pathway. We also found
      that TC21 interacted and formed complex with PI3-K. Mutations in the GTP-binding
      region of TC21, which enhanced GTP-binding potential of this protein, also
      stimulated its association with PI3-K, suggesting that PI3-K may preferentially
      interact with the GTP-bound form. Suppression of PI3-K and Akt by specific
      inhibitors LY294002 and Wortmannin reversed TC21-induced transformation.
      Likewise, inhibition of PI3-K activity by the PI3-K phosphotase PTEN reduced TC21
      mediated focus formation in NIH3T3 cells. Investigation of TC21's effect on cell
      survival revealed that mutant-TC21 expressing cells were more resistant to
      etoposide- and cisplatin-induced cell death, and this was associated with the
      activation of anti-apoptotic protein NF-kappaB, a downstream target of Akt.
      Treatment of PI3-K inhibitor LY294002 significantly suppressed TC21-mediated NF
      kappaB activation. In conclusion, we have identified PI3-K as an effector of TC21
      and demonstrated that the PI3-K/Akt signaling pathway plays important roles in
      TC21-mediated transformation and cell survival.

PMID- 11850824
TI  - Downregulating PKC delta provides a PI3K/Akt-independent survival signal that
      overcomes apoptotic signals generated by c-Src overexpression.
AB  - 3Y1 rat fibroblasts overexpressing the tyrosine kinase c-Src (3Y1(c-Src) cells)
      become transformed by downregulation of protein kinase C delta (PKC delta).
      However, when 3Y1(c-Src) cells were subjected to serum withdrawal, they underwent
      apoptosis via a cytochrome c/caspase 9 pathway. In contrast, neither parental nor
      v-Src-transformed 3Y1 cells underwent apoptosis when subjected to serum
      withdrawal. If PKC delta was downregulated, the apoptotic phenotypes induced by
      serum withdrawal in the 3Y1(c-Src) cells were suppressed. The apparent survival
      signal generated by PKC delta downregulation was independent of the
      phosphatidylinositol-3-kinase (PI3K)/Akt survival pathway. Collectively, these
      data indicate that (1) c-Src overexpression renders cells sensitive to apoptotic
      stress, and (2) that downregulation of PKC delta provides a novel PI3K/Akt
      independent survival signal capable of suppressing apoptotic signals.

PMID- 11850825
TI  - C-Cbl binds the CSF-1 receptor at tyrosine 973, a novel phosphorylation site in
      the receptor's carboxy-terminus.
AB  - The colony-stimulating factor-1 (CSF-1) receptor is a protein-tyrosine kinase
      that regulates the proliferation and differentiation of monocyte and macrophage
      precursors. Binding of CSF-1 to its receptor results in activation of the kinase
      domain and autophosphorylation on a number of tyrosine residues. Phosphorylated
      tyrosine residues function as binding sites for SH2 domain-containing signaling
      proteins. It is known that activated receptors are internalized and degraded, but
      the mechanics of this process remain largely unknown. Recently, evidence has
      started to emerge that the ubiquitin-protein ligase c-Cbl is involved in CSF-1
      receptor degradation. In addition, there is evidence that the CSF-1 receptor
      carboxy-terminus is involved in down regulation of the receptor. Here we show
      that the c-Cbl tyrosine kinase-binding (TKB) domain binds in vitro and in vivo to
      the CSF-1 receptor. Binding is dependent on the receptor's protein-kinase
      activity. Deletion of the carboxy-terminus or mutation of Tyr 973 blocks binding.
      We further provide evidence that the CSF-1 receptor's carboxy-terminus is a
      substrate for autophosphorylation. Our observations are consistent with a model
      in which receptor autophosphorylation at Tyr 973 creates a binding site for c
      Cbl. Association of c-Cbl with the receptor leads to ubiquitination, followed by
      receptor degradation.

PMID- 11850826
TI  - Activation of ATM and phosphorylation of p53 by heat shock.
AB  - p53 protein is phosphorylated in response to various stresses. Here we examined
      phosphorylation of p53 protein in normal human diploid cells after heat shock at
      43 degrees C for 2 h. We found that heat shock stimulates phosphorylation of p53
      at Ser15 but not at Ser20, while X-irradiation at 4 Gy and 10 J/m(2) of UV
      induces phosphorylation of p53 at Ser15 and less significantly at Ser20.
      Increased phosphorylation of Ser15 was also observed in heat shocked GM638, the
      SV40-transformed human fibroblast cell line. Although X-ray irradiation induced
      phosphorylation of Ser6, 9, 20, and 37 in GM638 cells, heat shock did not affect
      the phosphorylation level of these serines. We observed little or no
      phosphorylation of p53 at Ser15 in two primary ataxia telangiectasia fibroblast
      cells, that are defective in ATM. Using an in vitro kinase assay, we confirmed
      that immunoprecipitated ATM from both heat-shocked and X-irradiated normal human
      diploid cells can phosphorylate p53 at Ser15 to a similar extent. These results
      indicate that heat shock induces phosphorylation of p53, especially at Ser15, and
      its phosphorylation is mediated by ATM kinase.

PMID- 11850827
TI  - Estrogen induction and overexpression of fibulin-1C mRNA in ovarian cancer cells.
AB  - Fibulin-1 is an extracellular matrix protein induced by estradiol in estrogen
      receptor (ER) positive ovarian cancer cell lines. Alternative splicing of fibulin
      1 mRNA results in four different variants named A, B, C and D that may have
      distinct biological functions. We studied the relative expression of fibulin-1
      mRNA variants and their estrogen regulation in human ovarian cancer cells. In
      ovarian tissues and cancer cell lines, fibulin-1C and -1D are the predominant
      forms, whereas fibulin-1A and -1B are weakly expressed. We developed a
      competitive PCR assay based on coamplification of fibulin-1C and -1D to study the
      relative expression of these fibulin-1 variants in human ovarian samples. In
      ovarian cancer cell lines and ovarian cancer samples, there was a marked increase
      in the fibulin-1C:1D and fibulin-1C:HPRT mRNA ratios as compared to normal
      ovaries. In the BG1 estrogen receptor positive ovarian cancer cell line, fibulin
      1C mRNA was induced by estradiol in a dose- and time-dependent manner. Since
      others and we have previously shown an increased expression of ERalpha as
      compared to ERbeta in ovarian cancer cells, we investigated whether ERalpha or
      ERbeta is involved in this induction. For this aim, MDA-MB-231 breast cancer cell
      line, which expresses both low basal levels of ERs and fibulin-1, was infected
      with recombinant ERalpha or ERbeta encoding adenovirus and treated with
      estradiol. Fibulin-1C was induced by estradiol in ERalpha- but not ERbeta
      infected cells, suggesting that fibulin-1C induction is mediated through ERalpha.
      In ovarian tumors, a trend towards a correlation between fibulin-1C and ERalpha
      expression levels was noted. In conclusion, this study showed an increased
      fibulin-1C:-1D mRNA ratio in ovarian cancer cells as compared to normal ovaries.
      This finding suggests that the C variant may be involved in ovarian
      carcinogenesis. Fibulin-1C overexpression may thus be a clue for the
      understanding of a putative role of estrogens in ERalpha promoted ovarian tumor
      progression.

PMID- 11850828
TI  - PARP-1 modifies the effectiveness of p53-mediated DNA damage response.
AB  - The tumour suppressor protein p53 plays a key role in the cell's decision to
      arrest the cell cycle or undergo apoptosis following a genotoxic insult. p53 is
      stabilized and activated after DNA damage, however the cascade of events
      signalling from DNA lesions to p53 stabilization and activation is still
      controversial. Poly (ADP-ribosylation) of different nuclear acceptors by PARP-1
      is an early event when a single strand DNA lesion is produced. We present here
      evidences that interplay between PARP-1 and p53 is dependent on the type of
      damage induced to DNA. Primary mouse embryonic fibroblasts derived from parp-1 -/
      mice exhibited decreased p53 accumulation and activation following gamma
      irradiation compared to parp-1 proficient cells. On the other hand, treatment
      with the single alkylating agent 2'-methyl-2'-nitrose-urea (MNU), resulted in the
      rapid and sustained accumulation and activation of p53 in parp-1-deficient cells,
      while very little accumulation was observed in parp-1 +/+ cells. After IR, the
      turnover of the p53 inhibitory protein MDM-2 is perturbed and the level of
      phosphorylation of p53 at serine-15 is blunted in parp-1 -/- cells. PARP-1 is
      determinant in the cytotoxic response to alkylating agents but only partially
      contributes to radiation-induced cell killing, as determined by colony forming
      assay. Altogether, these results suggest that PARP-1 participates in the p53
      response following irradiation, resides upstream of p53 and indirectly modulates
      the level of phosphorylation of key substrates in this pathway while treatment
      with MNU results in an enhanced p53-mediated response in parp-1-null cells.

PMID- 11850829
TI  - Selective loss of chromosome 11 in pheochromocytomas associated with the VHL
      syndrome.
AB  - By using comparative genomic hybridization (CGH), we characterized the genetic
      profiles of 36 VHL-related pheochromocytomas. We then compared the results with
      those of sporadic and MEN 2-related pheochromocytomas. In 36 VHL-related tumors,
      loss of chromosome 3 and chromosome 11 were found in 34 tumors (94%) and 31
      tumors (86%), respectively. There was significant concordance of deletions in
      chromosomes 3 and 11 (Kappa=0.64, P=0.0095), suggesting that they are involved in
      two different but necessary and complementary genetic pathways. The loss of
      chromosome 11 appeared to be specific for VHL-related pheochromocytoma as it was
      not present in any of the 10 VHL-related CNS hemangioblastomas studied and was
      significantly less common when compared with (a) sporadic pheochromocytomas from
      previously published results (13%; P=<0.0001), and (b) MEN 2-related
      pheochromocytomas from this and previously published studies (30%; P=0.0012). In
      summary, this is the first report of a novel consistent genetic alteration that
      is selected and specific for VHL-related pheochromocytoma, besides the two hits
      of the VHL gene.

PMID- 11850830
TI  - Endonuclein is a cell cycle regulated WD-repeat protein that is up-regulated in
      adenocarcinoma of the pancreas.
AB  - The transcript encoding endonuclein, the human homolog of yeast PWP1, was
      previously found up-regulated in pancreatic cancer tissue. By
      immunohistochemistry we detected a ubiquitous presence in several tissues
      examined: skin, liver, thyroid gland, heart muscle, neurons, kidney, bladder,
      pancreas, adrenal gland, ovary, uterus, testis and prostate gland. We especially
      noticed that normal pancreatic exocrine cells exhibited low protein levels while
      pancreatic adenocarcinoma cells revealed high levels. We found a heterogeneous
      subcellular distribution, especially with varying nuclear levels. In
      proliferating cells endonuclein protein expression and localization was cell
      cycle dependent, with increasing levels and nuclear focusing during the
      interphase toward mitosis. Ultrastructural analysis revealed ER and nuclear
      localization. Endonuclein contains five WD-repeats, indicating a putative role in
      crucial regulatory activities in the nucleus as well as in the ER.

PMID- 11850831
TI  - Conserved domains in the chicken homologue of BRCA2.
AB  - Germline mutation of the BRCA2 gene causes a high risk of developing breast and
      ovarian cancer. Although the BRCA2 protein has been implicated in homologous
      recombination (HR) of DNA and in transcription, it is still unclear how mutation
      leads to tumorigenesis. We have identified a non-mammalian homologue of BRCA2
      from chicken, which encodes a protein with 3397 amino acids (aa) and shows only
      40% identity to human BRCA2. However, comparison of the mammalian and chicken
      sequences revealed remarkably high homology in several segments. These include a
      N-terminal region (approximately 100 aa), which was previously shown to possess
      intrinsic transcriptional activity, and a C-terminal region (aa residue
      approximately 2480-approximately 3180 in human BRCA2), which has not been clearly
      assigned any function. In contrast, although the eight BRC repeats of mammalian
      BRCA2 are believed to play an important role in HR by interacting with Rad51, the
      BRC3, BRC5, and BRC6 repeats exhibit virtually no similarity to their mammalian
      counterparts. Among 311 missense mutations listed as unclassified variants in the
      NIH Breast Cancer Information Core database, only 83 of these sites are identical
      in chicken BRCA2. Thus, chicken BRCA2 may provide a means to identify domains and
      residues associated with cancer predisposition.

PMID- 11850832
TI  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) triggers
      apoptosis in normal prostate epithelial cells.
AB  - TRAIL is a pro-apoptotic cytokine believed to selectively kill cancer cells
      without harming normal ones. However, we found that in normal human prostate
      epithelial cells (PrEC) TRAIL is capable of inducing apoptosis as efficiently as
      in some tumor cell lines. At the same time, TRAIL did not cause apoptosis in
      several other human primary cell lines: aorta smooth muscle cells, foreskin
      fibroblasts, and umbilical vein endothelial cells. Compared to these primary
      cells, PrEC were found to contain significantly fewer TRAIL receptors DcR1 and
      DcR2 which are not capable of conducting the apoptotic signal. This result
      suggests that the unusual sensitivity of PrEC to TRAIL may result from their
      deficiency in anti-apoptotic decoy receptors. The protein synthesis inhibitor
      cycloheximide significantly enhanced TRAIL toxicity toward PrEC as measured by
      tetrazolium conversion but had little or no effect on other TRAIL-induced
      apoptotic responses. Although cycloheximide did not further accelerate the
      processing of caspases 3 and 8, it significantly enhanced cleavage of the caspase
      3 substrate gelsolin, indicating that in PrEC a protein(s) with a short half-life
      may inhibit the activity of the executioner caspases toward specific substrates.
      As the majority of prostate cancers are derived from epithelial cells, our data
      suggest the possibility that TRAIL could be a useful treatment for the early
      stages of prostate cancer.

PMID- 11850833
TI  - Association of SV40 with human tumors.
AB  - In 1994, PCR and protein studies suggested that SV40 DNA sequences and proteins
      were present in 29/48 (60%) USA human mesothelioma samples. Sequence analysis
      confirmed that the sequences were homologous to SV40. One year later, SV40 was
      also found in 5/9 human mesotheliomas, and in 1996 SV40 was also reported to be
      present in 1/3 of the tumor specimens examined. These reports, in combination
      with an earlier study in 1992 which had detected SV40 in human brain tumors,
      raised concerns that SV40 was associated with certain types of human tumors,
      specifically mesothelioma, bone, and brain tumors. These findings raised
      concerns, because these tumor types are the same malignancies that had been
      observed in animals injected with SV40. However, a study in 1996 and a
      presentation made at the International Mesothelioma Interest Group, IMIG in 1997
      failed to detect SV40 in mesotheliomas, suggesting the possibility that
      laboratory artifacts, such as PCR contamination, had caused the previous positive
      findings. In 1997, the FDA, the NIH, and the CDC organized an international
      conference in Bethesda to review the literature and to address the possibility
      that SV40 was present in, and was possibly the cause of, some human tumors. The
      results of that conference were reported the same year in a meeting review in
      Oncogene by Carbone and colleagues. Briefly, the consensus was that before
      accepting the possibility that SV40 was present in human tumors, a multi
      laboratory study needed to be conducted. It was recommended that a blinded multi
      laboratory study be directed by an independent scientist not previously
      associated with the controversial reports of SV40 in human specimens. It was also
      recommended that this study include laboratories that had reported positive
      findings as well as laboratories that had failed to detect SV40 in human
      specimens. Since 1997, about 30 independent reports have been published on this
      topic, including the multi-laboratory study. Evidence in favor and against a
      possible association of SV40 with human cancer was reviewed at an international
      consensus meeting at the University of Chicago on 20, 21 April 2001, entitled
      "Malignant Mesothelioma: Therapeutic Options and the Role of SV40, 2001". The
      main focus was the association of SV40 with mesothelioma and other human tumors.
      At the end of the meeting, a panel discussion, which included independent experts
      who had not published on this topic, critically reviewed the evidence presented
      at the meeting. The results of the meeting and of the final panel discussion are
      outlined below.

PMID- 11850834
TI  - Oncogenic potential of the DNA replication licensing protein CDT1.
AB  - The expression of a gene, designated as Retroviral insertion site (Ris)2, was
      activated by retroviral DNA integration in an immortalized primitive erythroid
      cell line, EB-PE. Ris2 was also expressed at high levels in all human tumor cell
      lines analysed. Consistently, NIH3T3 fibroblasts overexpressing Ris2 formed
      tumors in Rag2 -/- mice when injected subcutaneously. The putative RIS2 protein
      shows a high sequence similarity to Xenopus CDT1, Drosophila DUP, and human CDT1,
      a newly identified DNA replication licensing protein, suggesting that Ris2 is a
      mouse homologue of CDT1. Cells overexpressing Ris2/Cdt1 exhibited a quicker entry
      into S phase when released from serum starvation compared to controls. Our
      results suggest that CDT1, an essential licensing protein for DNA replication,
      can function as an oncogene in mammals.

PMID- 11850836
TI  - Somatic point mutation of the wild-type allele detected in tumors of patients
      with VHL germline deletion.
AB  - The majority of patients with Von Hippel-Lindau (VHL) disease are affected by a
      VHL germline mutation involving one copy of the VHL gene. Loss of heterozygosity
      of the second VHL allele can be consistently demonstrated in tumor tissue from
      these patients, suggesting that allelic deletion is a very early or even
      initiating event for tumorigenesis. Approximately 20% of VHL disease patients,
      however, exhibit germline deletion of one entire copy or at least a substantial
      part of the VHL gene. To investigate the nature of the "second genetic hit" in
      this patient population, we analysed two renal cell carcinomas and one CNS
      hemangioblastoma from three unrelated patients for genetic changes of the second
      copy of the VHL gene. All three tumors showed retention of one VHL allele by
      FISH. Single-strand conformation polymorphism and mutation analysis of
      microdissected tumor DNA revealed somatic point mutations of the wild-type VHL
      copies in each of the three tumors. The results indicate that the "two hit model"
      is equally applicable to patients with VHL germline mutation and VHL germline
      deletion. In contrast to tumors from patients with VHL germline mutation,
      however, point mutations of the wild-type allele can be detected in tumors from
      patients with VHL germline deletion.

PMID- 11850837
TI  - p60(v-src) and serum control cell shape and apoptosis via distinct pathways in
      quail neuroretina cells.
AB  - We made use of QNR cells transformed by a thermosensitive (tsNY68) strain of the
      Rous sarcoma virus (RSV) to compare the effect of p60(v-src) and serum in
      cultured nerve cells. In this system, both p60(v-src) heat inactivation and serum
      removal resulted in growth arrest in G1. In both cases, growth arrest was
      reversible since cell proliferation was rapidly re-induced following respectively
      p60v-src renaturation or serum re-addition. However, cells did not fully recover
      their ability to grow in soft agar, suggesting that, in contrast to the cell
      cycle machinery, the transforming capacities of these cells have been
      irreversibly altered. We found that p60(v-src) kinase activity prevented
      detachment from the substratum and cell death following serum removal. Thermal
      inactivation of p60(v-src) at restrictive temperature (41.5 degrees C), but not
      serum removal, resulted in dramatic morphological changes, which occurred 4 h
      after temperature shift up to 41.5 degrees C. Later on, typical features of
      apoptotic cells could be observed. Cell death was greatly reduced by the caspase
      3 inhibitor ZVAD.FMK, but not by the caspase-1 inhibitor Ac-YVAD.CHO. Together,
      these results suggested that p60(v-src) and serum factors act on distinct
      pathways, at least in part. In an attempt to identify the signalling pathways
      involved in the cell response to p60(v-src) down regulation, we found that Erk
      and Rac were rapidly inactivated following temperature shift up to 41.5 degrees
      C. Thus, the combined effects of p60(v-src) and serum factors on the cytoskeleton
      dynamics and the apoptosis machinery are essential for full neoplastic
      transformation of neuroretina cells.

PMID- 11850835
TI  - Ansamycin antibiotics inhibit Akt activation and cyclin D expression in breast
      cancer cells that overexpress HER2.
AB  - Ansamycin antibiotics, such as 17-allylaminogeldanamycin (17-AAG), bind to Hsp90
      and regulate its function, resulting in the proteasomal degradation of a subset
      of signaling proteins that require Hsp90 for conformational maturation. HER2 is a
      very sensitive target of these drugs. Ansamycins cause RB-dependent G1 arrest
      that is associated with loss of D-cyclins via a PI3 kinase, Akt dependent
      pathway. Downregulation of D-cyclin was due, in part, to loss of Akt expression
      in response to drug. Moreover, in HER2 overexpressing breast cancer cells, 17-AAG
      caused rapid inhibition of Akt activity prior to any change in Akt protein.
      Ansamycins caused rapid degradation of HER2 and a concomitant loss in HER3
      associated PI3 kinase activity. This led to a loss of Akt activity,
      dephosphorylation of Akt substrates, and loss of D-cyclin expression.
      Introduction into cells of a constitutively membrane bound form of PI3 kinase
      prevented the effects of the drug on Akt activity and D-cyclins. Thus, in breast
      cancer cells with high HER2, Akt activation by HER2/HER3 heterodimers is required
      for D-cyclin expression. In murine xenograft models, non-toxic doses of 17-AAG
      markedly reduced the expression of HER2 and phosphorylation of Akt and inhibited
      tumor growth. Thus, pharmacological inhibition of Akt activation is achievable
      with ansamycins and may be useful for the treatment of HER2 driven tumors.

PMID- 11850838
TI  - Adenoviral delivery of p53 gene suppresses expression of collagenase-3 (MMP-13)
      in squamous carcinoma cells.
AB  - Squamous cell carcinomas (SCCs) of the head and neck are characterized by high
      tendency to invade locally and metastasize to lymph nodes. SCC cells express
      several matrix metalloproteinases (MMPs) and they often harbor mutations in p53
      tumor suppressor gene. Collagenase-3 (MMP-13) is specifically expressed by tumor
      cells of SCCs and it apparently plays an important role in their invasion and
      metastasis. We used adenoviral gene delivery to examine the effect of wild-type
      p53 on MMP-13 expression in four head and neck SCC cell lines with mutated p53.
      Adenoviral delivery of p53 resulted in potent inhibition in production of proMMP
      13 (by 71 to 92%) and collagenase-1 (MMP-1) (by 27 to 93%) by all cell lines in
      24 h, whereas production of gelatinase-A (MMP-2) and gelatinase-B (MMP-9) was not
      altered. Adenoviral expression of p53 also suppressed invasion of SCC cells
      through Matrigel by 35%. Expression of cyclin-dependent kinase inhibitor
      p21(Waf1/Cip1) was induced 24 h after p53 gene delivery in all SCC cell lines,
      except one, which lacked detectable p21(Waf1/Cip1) expression. Number of viable
      cells was not altered and no apoptotic cells were seen 24 h after p53 delivery.
      These results show, that wild-type p53 potently inhibits expression of MMP-13 and
      MMP-1 by SCC cells independently of its pro-apoptotic effect. Together these
      results indicate, that p53 exerts a bi-phasic tumor suppressor effect on SCC
      cells: inhibition of cell invasion followed by induction of programmed cell
      death.

PMID- 11850839
TI  - Concomitant down-regulation of BRM and BRG1 in human tumor cell lines:
      differential effects on RB-mediated growth arrest vs CD44 expression.
AB  - Mammalian cells express two homologs of the SWI2 subunit of the SWI/SNF chromatin
      remodeling complex called BRG1 and BRM. Whether the SWI/SNF complexes formed by
      these two subunits perform identical or different functions remains an important
      question. In this report, we show concomitant down-regulation of BRG1 and BRM in
      six human tumor cell lines. This down-regulation occurs at the level of mRNA
      abundance. We tested whether BRM could affect aberrant cellular functions
      attributed to BRG1 in tumor cell lines. By transient transfection, we found that
      BRM can restore RB-mediated cell cycle arrest, induce expression of CD44 protein
      and suppress Cyclin A expression. Therefore, BRM may be consistently down
      regulated with BRG1 during neoplastic progression because they share some
      redundant functions. However, assorted tissues from BRM null/BRG1-positive mice
      lack CD44 expression, suggesting that BRM-containing SWI/SNF complexes regulate
      expression of this gene under physiological conditions. Our studies further
      define the mechanism by which chromatin-remodeling complexes participate in RB
      mediated cell cycle arrest and provide additional novel evidence that the
      functions of SWI/SNF complexes containing BRG1 or BRM are not completely
      interchangeable.

PMID- 11850840
TI  - Facilitation of adenoviral wild-type p53-induced apoptotic cell death by
      overexpression of p33(ING1) in T.Tn human esophageal carcinoma cells.
AB  - To investigate the effect of p33(ING1) on wild-type p53 gene therapy, T.Tn human
      esophageal carcinoma cells were stably transfected with p33(ING1) cDNA. Infection
      with Ad-p53 (recombinant adenovirus containing wild-type p53) into p33
      transfected cells reduced cell viability, while infection with empty vector had
      little effect. This reduced viability was shown to be due to apoptotic cell death
      by the TUNEL (terminal deoxynucleotidyl transferase-mediated nick end-labeling)
      assay. Following infection with Ad-p53, levels of p53 were similar in p33
      expressing cells and in the parental line. However, levels of p21 and Mdm2 were
      elevated in p33-transfected cells. Nonetheless, this enhanced expression of Mdm2
      appeared to be ineffective in downregulating p53. Transient transfection with
      mutant Mdm2 prior to Ad-p53 infection provided a significant protection as
      compared with cells transfected with wild-type Mdm2. These results imply a
      synergistic effect between p33 and p53 in the induction of apoptosis of human
      esophageal carcinoma cells. A role for Mdm2 in this synergism is suggested.

PMID- 11850841
TI  - Preferential loss of Death Associated Protein kinase expression in invasive
      pituitary tumours is associated with either CpG island methylation or homozygous
      deletion.
AB  - Death Associated Protein kinase (DAP kinase) a novel calmodulin-dependent
      serine/threonine kinase was first identified as a positive mediator of programmed
      cell death. Loss of DAP kinase expression was first demonstrated in highly
      metastatic cells, whilst re-expression of the protein resulted in delayed local
      tumour growth and a decreased incidence of metastasis. Although loss of DAP
      kinase expression has been reported in several cell lines derived from human
      malignancies the mechanisms responsible have not been defined. In this study we
      have examined 32 sporadic pituitary tumours for expression of the DAP kinase
      protein and transcript. In addition, we examined the methylation and deletion
      status of the DAP kinase CpG island as possible mechanisms for the inactivation
      of the DAP kinase gene. Eleven of 32 (34%) tumours had undetectable DAP kinase
      expression, by Western blot and/or RT-PCR analysis. Loss of DAP kinase expression
      was significantly (P=0.004) associated with invasive tumours (10 of 17; 59%)
      compared to their non-invasive (1 of 15; 7%) counterparts. Of 11 tumours that
      failed to express DAP kinase, five (45%) showed de novo methylation of the CpG
      island contained within the promoter region, while four (36%) had evidence of
      homozygous deletion of this region. Statistical analysis showed that loss of DAP
      kinase expression was significantly (P=<0.001) associated with methylation or
      deletion of the DAP kinase CpG island. With two exceptions, none of the remaining
      tumours or five histologically normal post-mortem pituitaries examined had
      evidence of methylation or deletion within this region. To our knowledge this is
      the first report that describes two mutually exclusive mechanisms associated with
      loss of DAP kinase gene expression. In addition, we also show that loss of the
      DAP kinase protein and associated genetic aberrations preferentially segregates
      with tumours that show an invasive phenotype.

PMID- 11850842
TI  - Specific association between alcohol intake, high grade of differentiation and
      4q34-q35 deletions in hepatocellular carcinomas identified by high resolution
      allelotyping.
AB  - One of the most frequent deletions in hepatocellular carcinoma (HCC) is that
      involving the long arm of chromosome 4 (30 to 70% of the cases). These
      chromosomal deletions are closely related to hepatitis B virus (HBV) infection. A
      tumor suppressor gene (TSG) located on 4q has been proposed in liver
      carcinogenesis, but has not been identified as yet. Despite previous LOH studies
      focused on 4q in HCC, a clear minimal common region of deletion (MCRD) could not
      be delimited. To further investigate the role of chromosome 4q LOH in the
      pathogenesis of HCC, 85 microsatellite markers spanning chromosome 4q were
      systematically analysed in a series of 154 well-characterized primary liver
      tumors. In 59 tumors (38%), LOHs were observed for at least two adjacent markers.
      Analysis of 31 tumors demonstrating a partial or interstitial 4q deletion allowed
      to define three MCRDs of 15, 9 and 8 Mb at the 4q22, 4q34 and 4q35 regions,
      respectively. Seven putative candidate genes located in 4q22, DAPP1, BMPR1B,
      PKD2, HERC3, SMARCAD1, CEB1 and ENH were screened for mutations but no somatic
      alterations were identified. Search for relationships between the specific
      regions of deletion and clinical parameters showed a significant association
      between loss of the 4q34-35 region with alcohol intake (P=0.005) and with high
      grade of differentiation (P=0.02). These results are in contrast with the close
      association between HBV infection and the whole 4q LOH and reveal heterogeneity
      of 4q LOH in relation to different risk factors. In the light of these new
      findings, which link different 4q LOH regions to different etiologic factors, the
      molecular mechanisms underlying 4q deletions in HCC and the targeted gene(s)
      remain to be identified.

PMID- 11850843
TI  - LATS1 tumor suppressor regulates G2/M transition and apoptosis.
AB  - The LATS1 gene is a mammalian member of the novel lats tumor suppressor family.
      Both lats mosaic flies and LATS1 deficient mice spontaneously develop tumors. Our
      previous studies have shown that inactivation of Drosophila lats leads to up
      regulation of cyclin A in the fly, and the human LATS1 protein associates with
      CDC2 in early mitosis in HeLa cells, suggesting that the lats gene family may
      negatively regulate cell proliferation by modulating CDC2/Cyclin A activity. We
      demonstrate here that transduction of the human breast cancer cell MCF-7 with
      recombinant LATS1 adenovirus (Ad-LATS1), but not with EGFP adenovirus (Ad-EGFP),
      inhibits in vitro cell proliferation. Ectopic expression of LATS1 in MCF-7 cells
      specifically down-regulates Cyclin A and Cyclin B protein levels and dramatically
      reduces CDC2 kinase activity, leading to a G2/M blockade. Furthermore, Ad-LATS1
      suppresses anchorage-independent growth of MCF-7 cells in soft agar and tumor
      formation in athymic nude mice. We also demonstrate that ectopic expression of
      LATS1 in MCF-7 cells and human lung cancer cell H460 up-regulates the level of
      BAX proteins and induces apoptosis. Finally, we show that LATS1 kinase activity
      is required for its ability to inhibit cell growth and induce apoptosis. The
      results indicate that the LATS1 tumor suppressor may play an important role in
      the control of human tumor development and that LATS1 suppresses tumorigenesis by
      negatively regulating cell proliferation and modulating cell survival.

PMID- 11850844
TI  - Inhibition of tumour cell growth by hyperforin, a novel anticancer drug from St.
      John's wort that acts by induction of apoptosis.
AB  - Hyperforin is a plant derived antibiotic from St. John's wort. Here we describe a
      novel activity of hyperforin, namely its ability to inhibit the growth of tumour
      cells by induction of apoptosis. Hyperforin inhibited the growth of various human
      and rat tumour cell lines in vivo, with IC(50) values between 3-15 microM.
      Treatment of tumour cells with hyperforin resulted in a dose-dependent generation
      of apoptotic oligonucleosomes, typical DNA-laddering and apoptosis-specific
      morphological changes. In MT-450 mammary carcinoma cells hyperforin increased the
      activity of caspase-9 and caspase-3, and hyperforin-mediated apoptosis was
      blocked by the broad-range caspase inhibitor zVAD.fmk. When added to MT-450
      cells, hyperforin, but not paclitaxel, induced a rapid loss of the mitochondrial
      transmembrane potential Deltapsi(m), and subsequent morphological changes such as
      homogenization and vacuolization of mitochondria. Monitoring of Deltapsi(m)
      revealed that the hyperforin-mediated mitochondrial permeability transition can
      not be prevented by zVAD.fmk. This indicates that mitochondrial permeabilization
      is a cause rather than a consequence of caspase activation. Moreover, hyperforin
      was capable of releasing cytochrome c from isolated mitochondria. These findings
      suggest that hyperforin activates a mitochondria-mediated apoptosis pathway. In
      vivo, hyperforin inhibited the growth of autologous MT-450 breast carcinoma in
      immunocompetent Wistar rats to a similar extent as the cytotoxic drug paclitaxel,
      without any signs of acute toxicity. Owing to the combination of significant
      antitumour activity, low toxicity in vivo and natural abundance of the compound,
      hyperforin holds the promise of being an interesting novel antineoplastic agent
      that deserves further laboratory and in vivo exploration.

PMID- 11850845
TI  - Mechanisms of Interferon-alpha induced apoptosis in malignant cells.
AB  - Interferon alpha (IFNalpha) has been used in the treatment of several types of
      cancer for almost 30 years, yet the mechanism(s) responsible for its anti-tumoral
      action remains unknown. A variety of cellular responses, including inhibition of
      cell growth and induction of apoptosis are induced by IFNs, and apoptotic
      induction by this cytokine has been proposed to be of importance for both its
      anti-tumoral in addition to its anti-viral responses. The aim of the present
      study was to delineate the pathways activated during IFNalpha-induced apoptosis
      in malignant cell lines. We found that apoptosis induced by IFNalpha was
      associated with activation of caspases-1, -2, -3, -8 and -9 and that this
      activation was a critical event. Caspase-3 activation was dependent on activity
      of caspases-8 and -9, moreover, activation of caspase-8 seems to be the upstream
      event in IFNalpha-induced caspase cascade. We also found loss of mitochondrial
      membrane potential as well as release of cytochrome c post IFN-treatment, clearly
      implicating the involvement of mitochondria in IFN-mediated apoptosis.
      Furthermore, IFNalpha-induced apoptosis was found to be independent on
      interactions between the Fas-receptor and its ligand. These studies form the
      basis for further investigations aiming to improve IFN therapy and the
      development of future strategies to overcome the IFN resistance observed in some
      malignancies.

PMID- 11850846
TI  - Phosphatidylinositol 3-kinase is essential for the proliferation of
      lymphoblastoid cells.
AB  - B-cell lymphoma, which is increasing world wide, includes such varied conditions
      as post-transplant lymphoproliferative disease (PTLD) and Burkitt's lymphoma.
      This study has characterized a role for the signalling molecule
      phosphatidylinositol 3-kinase, PI3K, in the regulation of growth and survival of
      immortalized B-lymphocytes. Burkitt's lymphoma cells die rapidly following
      inhibition of PI3K with LY294002, a chemical inhibitor. Furthermore, Epstein-Barr
      virus (EBV) immortalized B-cells, lymphoblastoid cell lines, which are a model of
      PTLD, do not die but are growth inhibited. This growth inhibition is due to an
      accumulation at G1 phase of the cell cycle and is paralleled by a loss of E2F
      transcriptional activity, which is essential for cell cycle entry. An active form
      of PI3K promotes E2F transcriptional activity in lymphoblastoid cell lines.
      Treatment of LCL with LY294002 causes a reduction of the expression of both
      cyclin D2 and cyclin D3, two key cyclins required for cell cycle progression but
      does not affect the expression of the EBV latent genes, EBNA2A or LMP-1. LY294002
      also causes an increase in p27kip1, a cyclin dependent kinase inhibitor and
      results in the dephosphorylation of members of the pocket protein family. These
      data describe a mechanism by which PI3K plays a role in B-lymphocyte growth and
      suggests that a pathway from PI3K to D-type cyclin expression may provide
      diagnostic or treatment opportunities.

PMID- 11850847
TI  - Oncogene cooperativity in Friend erythroleukemia: erythropoietin receptor
      activation by the env gene of SFFV leads to transcriptional upregulation of PU.1,
      independent of SFFV proviral insertion.
AB  - Cancer is a multi-step, multi-genetic event. Whether oncogenic mutations
      cooperate with one another to transform cells and how is not well understood. The
      Friend murine retroviral erythroleukemia model involves mitogenic activation of
      the erythropoietin receptor (EpoR) by the virus env gene (F-gp55), aberrant over
      expression of the transcription factor PU.1, and inactivating mutations in p53.
      In this report we demonstrate that concurrent expression of F-gp55 and PU.1 in
      erythroid target cells, in vivo, cooperate to accelerate erythroleukemia
      induction. Early in the disease, prior to the detection of clonal leukemic cells,
      activation of the EpoR by F-gp55, but not erythropoietin, resulted in
      transcriptional upregulation of PU.1 through a trans regulatory mechanism. This
      could occur in the absence of an integrated provirus within the PU.1 gene locus.
      The regulation of PU.1 transcription in established erythroleukemia cell lines
      differed depending upon the level of PU.1 protein present. Our results suggest
      that the action of F-gp55 contributes to both early and late stages of Friend
      erythroleukemia and that persistence of F-gp55 expression may be required not
      only to initiate erythroleukemia but to also maintain erythroleukemia following
      Friend virus infection.

PMID- 11850848
TI  - p21B, a variant of p21(Waf1/Cip1), is induced by the p53 family.
AB  - Alternative splicing or expression from an alternate promoter can produce
      variants of a gene. To determine whether the p21(Waf1/Cip1) locus is regulated by
      these mechanisms, we searched for and found two transcripts, p21B and p21C, that
      are expressed from an alternate promoter in the first intron of the p21 gene.
      While p21C encodes the p21 cyclin-dependent kinase inhibitor, p21B encodes a
      novel protein and the transcript is ubiquitously expressed in 16 human tissues
      tested. Like p21, both p21B and p21C are induced by DNA damage, p53, and other
      p53 family members through a proximal p53 response element in the promoter of
      p21B and p21C. However, unlike p21, which induces cell cycle arrest, we found
      that overexpression of p21B induces apoptosis. These findings indicate that the
      p21 locus expresses at least two structurally distinct, but functionally related,
      variants of the p21 gene from discrete promoters.

PMID- 11850849
TI  - Identification of RB1CC1, a novel human gene that can induce RB1 in various human
      cells.
AB  - Multidrug resistance to anti-cancer agents (MDR) is a major barrier to successful
      cancer treatment. Current knowledge about genes that contribute to MDR is
      limited, however, and its mechanisms remain unclear. To identify genes involved
      in MDR, we performed differential display analysis and isolated a novel human
      gene, RB1CC1 (RBI-inducible Coiled-Coil 1). The 6.6-kb RB1CC1 cDNA encodes a
      putative 1594-amino-acid protein that contains a nuclear localization signal, a
      leucine zipper motif and a coiled-coil structure. Western blot analysis and
      immunocytochemical staining with anti-RB1CC1 antibody showed that endogenously
      expressed RB1CC1 protein localized to the nucleus. In MDR variants of human
      osteosarcoma cells, RB1CC1 expression increased in response to doxorubicin
      induced cytotoxic stress and remained elevated for the duration of drug
      treatment. RB1CC1 expression levels correlated closely with those of RB1
      (retinoblastoma 1) in cancer cell lines as well as in various normal human
      tissues. Moreover, introduction of wild-type RB1CC1 significantly induced RB1
      expression in human leukemic cells. These data suggest that RB1CC1 may be a key
      regulator of RB1 gene expression.

PMID- 11850851
TI  - Monoclonal antibodies raised against Xenopus p53 interact with human p73.
AB  - The p53 tumor suppressor gene belongs to a multigene family that includes two
      paralogues, p63 and p73. The structure of the p63 and p73 genes is quite similar,
      but both have common activities with p53, such as DNA binding and
      transactivation. Both p53 and p73 bind to mdm2, but only p53 is degraded through
      the activity of mdm2. p63 neither binds to nor is degraded by mdm2 despite
      important conservation in the key interacting residues. Using a panel of
      monoclonal antibodies raised against human and Xenopus p53, we have been able to
      find several antibodies that cross-react strongly with human p73. These
      antibodies react both with exogenous p73 expressed in mammalian cells and with
      endogenous p73. Interestingly, all these antibodies react with the same epitope
      localized in the amino-terminus of p53, but have no cross-reaction with p63. This
      epitope corresponds to the exact mdm2 binding site to p53. These antibodies
      inhibit the interaction between either p53 or p73 and mdm2, and may be useful
      tools for the study of these proteins. Furthermore, our studies suggest that
      there exist specific spatial requirements for the interaction between p53 or p73
      and mdm2.

PMID- 11850850
TI  - Cross-talk between Akt, p53 and Mdm2: possible implications for the regulation of
      apoptosis.
AB  - The p53 tumor suppressor protein and the Akt/PKB kinase play important roles in
      the transduction of pro-apoptotic and anti-apoptotic signals, respectively. We
      provide evidence that conflicting signals transduced by Akt and p53 are
      integrated via negative feedback between the two pathways. On the one hand, the
      combination of ionizing radiation and survival factor deprivation, which leads to
      rapid apoptosis of IL-3 dependent DA-1 cells, entails a caspase- and p53
      dependent destruction of Akt. This destruction of Akt is not a secondary
      consequence of apoptosis, since it is not seen when the same cells are triggered
      to undergo apoptosis under different conditions. On the other hand upon serum
      stimulation, when Akt becomes active and enhances cell survival, phosphorylation
      occurs at an Akt consensus site (serine 166) within the Mdm2 protein, a key
      regulator of p53 function. Taken together, our findings suggest that depending on
      the balance of signals, p53-dependent downregulation of Akt may promote an
      irreversible commitment to apoptotic cell death, whereas effective recruitment of
      Akt by appropriate survival signals may lead to activation of Mdm2, inactivation
      of p53, and eventually inhibition of p53-dependent apoptosis.

PMID- 11850852
TI  - [Psychotherapy and psychosomatic - a unitary field?].

PMID- 11850854
TI  - [Evaluation of the bern day treatment programme and its position in the
      psychiatric network].
AB  - The Bern Day Treatment Programme offers cognitive-behavioural treatment to
      patients suffering from depression, eating disorders, anxiety disorders, and
      personality disorders. Treatment duration ranges from 12 to 20 weeks. Its concept
      is described in comparison to other similar institutions. To evaluate the
      programme the Beck Depression Inventory (BDI), the Symptom Check List (SCL-90-R),
      and the Change in Life Areas (VLB) were administered to 89 patients at admission
      and discharge. Their analyses revealed high symptom levels at admission and a
      significant improvement during treatment. Patients with personality disorders
      show less improvement in the VLB than patients without personality disorders. The
      results of the SCL-90-R indicate that the symptom levels at admission and the
      symptom reductions during treatment are similar to those of patients treated in
      inpatient units or in diagnostically specialised day treatment programmes. The
      Bern Day Treatment Programme seems to be feasible for highly impacted patients
      with non-psychotic disorders and might be a useful model for areas with low
      population density.

PMID- 11850853
TI  - [Predicting long-term outcome of in-patient psychosomatic treatment].
AB  - Abstract. The outcome of in-patient psychosomatic treatment was evaluated by
      longitudinal assessment at hospital admission, discharge, and 1-year-follow-up.
      Out of n = 1829 patients, n = 712 responded (38.9 %). Response rates co-varied
      with duration of in-patient treatment. Responder-analyses characterise the sample
      as fairly representative. Outcome criteria included standardised measures of
      complaints, mood quality, global quality of life, life satisfaction, everyday
      functioning, and social integration. Disease-related parameters (duration of
      illness, medical certification, number of doctors consulted, number of somatic
      resp. psychosocial diagnoses) and generalised outcome expectancies (self
      efficacy, optimism, pessimism) were included as predictors. Patients'
      retrospective estimations at follow-up as well as longitudinal assessments show a
      successful and mostly stable therapy outcome. Negative moods and complaints show
      a new increase at follow-up, though, still remaining below the level at hospital
      admission. Although there is much accordance among the diagnostic groups,
      patients with anxiety disorders (ICD-10: F40/41) and patients with adaptation
      disorders (F43) show distinctly varying courses. Regression analyses yield
      specific correlations between disease-related parameters and long-term outcome:
      Duration of treatment does not predict treatment outcome. The number of somatic
      diagnoses is a predictor of complaints, the number of psychosocial diagnoses a
      predictor of negative moods at follow-up. Pessimism and - to a lesser degree -
      self-efficacy prove to significantly predict numerous outcome criteria.
      Generalised expectancies should be considered in the process of prognosis and
      differential indication.

PMID- 11850855
TI  - [Changes of body image and body awareness in eating-disorder and non eating
      disorder patients after inpatient-therapy].
AB  - Altered body image and body awareness have significant clinical implications not
      only for patients with eating disorders. We evaluated therapy-outcome including
      distortions in body image in 61 inpatients using two instruments assessing body
      image (FKB-20 Clement and Lowe, and FBeK Strauss and Richter-Appelt ). Eating
      disorder subjects, as expected, showed the most severely disturbed body image
      with negative attitudes towards their own body and restricted body dynamics.
      While body image improved over all diagnostic groups after treatment, anorectic
      patients improved less than others. This finding confirms the clinical
      observation of the limited therapeutic influence on body image distortions in
      anorectic patients. Our results show, that the body image questionnaire FKB-20
      discriminates well between healthy and psychosomatically diseased patients and is
      a suitable instrument for process- and outcome-evaluation.

PMID- 11850856
TI  - [Coping-activities of stroke patients: intensity and effectiveness].
AB  - This study longitudinally examines the intensive and effective ways of coping in
      a cohort of 63 stroke patients (aged 38 - 85 yrs.). The coping activities of the
      stroke patients are investigated with the "Freiburg Questionnaire of Coping with
      Illness (FQCI)". In the acute phase (t1), especially the compliance-focused
      coping strategies are very often used, whereas the problem-focused, self
      constructive strategies leading to a quest for sense are only used quite often.
      Three months later (t2), compliance- and problem-focused coping strategies are
      employed with less intensity, the self-constructive ones, however, in a more
      intensive way. The strategies leading to a quest for sense are hardly employed in
      an intensive way any longer. A subjective estimation made by the examined stroke
      patients shows that the most effective coping strategies in the acute phase (t1)
      are problem- and compliance-focused. Self-constructive coping strategies come
      second and strategies with regard to a quest for sense only third in view of
      their effectiveness. Three months later (t2), the effective coping strategies are
      still problem-focused but only to a very small degree, while the effectiveness of
      compliance-focused strategies is lost completely. The self-constructive coping
      behaviour will now become the most effective one, a behaviour which proves to be
      even more inclined to a quest for sense than in the acute phase.

PMID- 11850858
TI  - 2002 guidelines for the use of antimicrobial agents in neutropenic patients with
      cancer.

PMID- 11850859
TI  - Survival of patients with pulmonary tuberculosis: clinical and molecular
      epidemiologic factors.
AB  - Using restriction fragment-length polymorphism data, we conducted a retrospective
      cohort study of 139 adult patients with pulmonary tuberculosis to investigate the
      clinical impact of Mycobacterium tuberculosis infection with a clustered isolate.
      The cumulative all-cause mortality rate during treatment was 21%. Patients with
      clustered DNA fingerprint patterns had a reduced risk of death, compared with
      patients with unique patterns (hazard ratio [HR], 0.5; 95% confidence interval
      [CI], 0.2-1.1), but this finding was confounded by age (adjusted HR, 0.8; 95% CI,
      0.4-1.8). After adjustment for age, the strongest predictors of death were such
      underlying illnesses as diabetes mellitus, renal failure, chronic obstructive
      pulmonary disease, and human immunodeficiency virus infection. We conclude that
      comorbidity and immunosuppression are important predictors of survival for
      patients with pulmonary tuberculosis in an inner-city cohort. Recently
      transmitted infection, as determined by use of DNA fingerprinting to classify
      patients' isolates as being either clustered or unique, was not independently
      associated with death.

PMID- 11850860
TI  - Antibiotic-resistant gram-negative organisms in pediatric chronic-care
      facilities.
AB  - This study was designed to define the prevalence of colonization with antibiotic
      resistant gram-negative rectal specimens were obtained from subjects residing in
      2 pediatric extended-care facilities and were processed to identify gram-negative
      organisms resistant to ceftazidime, gentamicin, meropenem, and piperacillin
      tazobactam. Horizontal transmission was assessed by analyzing all resistant
      isolates by pulsed-field gel electrophoresis. Forty percent of subjects were
      colonized with >/=1 resistant bacillus; >60% of organisms were resistant to >/=2
      of the antibiotics tested. Colonization was disproportionate among residents with
      a tracheostomy or other prosthesis. More than 65% of colonized subjects shared 1
      organism with another resident, with cross-colonization occurring among both
      enteric and nonenteric species. Children residing in chronic-care facilities
      represent a large reservoir for resistant bacilli. Such colonization may be
      amenable to simple barrier infection-control procedures.

PMID- 11850862
TI  - Emerging infectious agents: do they pose a risk to the safety of transfused blood
      and blood products?
AB  - The blood supply is safer than it has been at any other time in recent history,
      and, in the context of other health care-related adverse events, the risks
      associated with blood transfusion are extremely small. The current high level of
      safety is the result of successive refinements and improvements in how blood is
      collected, tested, processed, and transfused; nonetheless, blood and plasma
      products remain vulnerable to newly identified or reemerging infections. In
      recent years, numerous infectious agents-including several newly discovered
      hepatitis viruses, the agents of transmissible spongiform encephalopathies, and
      tickborne pathogens-have been identified as potential threats to the safety of
      blood and plasma. Continued vigilance is critical to protect the blood supply
      from known pathogens and to monitor for the emergence of new infectious agents.
      Recent terrorist activities in the United States add new considerations to
      maintaining the safety and supply of blood. Education of clinicians and patients
      regarding the benefits and risks associated with the judicious use of blood and
      blood products can assist in informed decision making.

PMID- 11850861
TI  - Pathogenic Aspergillus species recovered from a hospital water system: a 3-year
      prospective study.
AB  - Nosocomial aspergillosis, a life-threatening infection in immunocompromised
      patients, is thought to be caused primarily by Aspergillus organisms in the air.
      A 3-year prospective study of the air, environmental surfaces, and water
      distribution system of a hospital in which there were known cases of
      aspergillosis was conducted to determine other possible sources of infection.
      Aspergillus species were found in the hospital water system. Significantly higher
      concentrations of airborne aspergillus propagules were found in bathrooms, where
      water use was highest (2.95 colony-forming units [cfu]/m(3)) than in patient
      rooms (0.78 cfu/m(3); P=.05) and in hallways (0.61 cfu/m(3); P=.03). A
      correlation was found between the rank orders of Aspergillus species recovered
      from hospital water and air. Water from tanks yielded higher counts of colony
      forming units than did municipal water. An isolate of Aspergillus fumigatus
      recovered from a patient with aspergillosis was genotypically identical to an
      isolate recovered from the shower wall in the patient's room. In addition to the
      air, hospital water systems may be a source of nosocomial aspergillosis.

PMID- 11850863
TI  - Reimmunization with 23-valent pneumococcal vaccine for patients infected with
      human immunodeficiency virus type 1: clinical, immunologic, and virologic
      responses.
AB  - We determined the immunogenicity and safety of reimmunization with the 23-valent
      polysaccharide pneumococcal vaccine in patients infected with human
      immunodeficiency virus type 1 (HIV-1). Patients immunized >5 years earlier
      (initially within 1 year of HIV-1 seroconversion) were randomized to receive
      vaccine (n=57) or placebo (n=30). Persons with recent HIV-1 seroconversion (n=14)
      were immunized for the first time. Preimmunization levels of capsule-specific
      immunoglobulin G were similar in all groups. Reimmunized patients showed a
      significantly lower frequency and magnitude of antibody responses compared with
      persons with recent HIV-1 seroconversion. Reimmunized patients did not show
      adverse virologic or immunologic changes, but some reported local discomfort
      (15%) or fever (8%). Thus, the limited responses after reimmunization of HIV-1
      infected patients with the current 23-valent vaccine mandates the need for a more
      effective reimmunization schedule, more immunogenic vaccines, or other behavioral
      and therapeutic interventions.

PMID- 11850864
TI  - Rates of postoperative complications among human immunodeficiency virus-infected
      women who have undergone obstetric and gynecologic surgical procedures.
AB  - Clinical observations indicate that human immunodeficiency virus (HIV)-positive
      women experience more postoperative problems than do HIV-negative women. To
      obtain a better estimate of the individual risk of postoperative morbidity among
      HIV-infected women, and to determine which procedures pose the greatest risk, we
      performed a retrospective case-control study in which we assessed the outcomes
      after 235 obstetric and gynecologic surgical procedures. For purposes of
      comparison, an HIV-negative control patient was matched for each of the 235
      surgical procedures performed, on the basis of the type of procedure and patient
      age. We found a significantly greater number of postoperative complications among
      the HIV-positive women. Higher complication rates occurred after abdominal
      surgery (odds ratio [OR], 3.6; P=.001) and curettage (OR, 7.7; P=.06). Among HIV
      infected women, the risk of complications was associated with immune status.
      Antiretroviral therapy and standard perioperative antibiotic prophylaxis did not
      decrease the risk of complications. Indications for performing abdominal surgery
      and curettage on HIV-infected women should be carefully weighed against the
      potential risk of postoperative complications.

PMID- 11850865
TI  - Severe nucleoside-associated lactic acidosis in human immunodeficiency virus
      infected patients: report of 12 cases and review of the literature.
AB  - Lactic acidosis is a rare but often fatal complication reported in some human
      immunodeficiency virus (HIV)-infected patients treated with nucleoside-analogue
      reverse-transcriptase inhibitors. We report a series of 12 patients with HIV
      infection treated with nucleoside analogues who developed unexplained metabolic
      acidosis. We have also reviewed 60 additional published cases. The aim of the
      present study is to describe the clinical picture, prognostic factors, and final
      outcome for nucleoside-associated lactic acidosis. The mortality rate is high:
      33% for our patients, and 57% for the patients described in the literature. In
      the multivariate analysis, a lactate serum level of >10 mM (odds ratio [OR],
      13.23; 95% confidence interval [CI], 2.96-59.25) was the only factor associated
      with higher mortality. The administration of specific therapy with cofactors
      against acidosis was associated with a lower mortality (OR, 0.17; 95% CI, 0.04
      0.73). We conclude that specific therapy with cofactors may improve the outcome
      for patients with this syndrome.

PMID- 11850866
TI  - Quantification of adenovirus DNA in plasma for management of infection in stem
      cell graft recipients.
AB  - We used a real-time polymerase chain reaction method for quantification of
      adenovirus to monitor the dynamics of viral DNA load in plasma in pediatric stem
      cell graft recipients. Two cases are described to demonstrate that detection and
      quantification of the adenovirus DNA load at regular intervals may be important
      to document the stage of adenovirus infection, to make decisions on clinical
      intervention, and to accurately monitor the response to antiviral therapy.

PMID- 11850867
TI  - Septic joint replacement: an orthopedic perspective.

PMID- 11850868
TI  - Criteria for treatment of prosthetic joint infection.

PMID- 11850870
TI  - Urine samples for rabies RNA detection in the diagnosis of rabies in humans.

PMID- 11850871
TI  - Kawasaki-like illness in Human Immuno-deficiency Virus-infected patients: is the
      etiologic agent the same as in pediatric Kawasaki disease?

PMID- 11850873
TI  - Cause and timing of death following meningitis in adults.

PMID- 11850875
TI  - The United States Food and Drug Administration and noninferiority margins in
      clinical trials of antimicrobial agents.

PMID- 11850876
TI  - [Obesity: gradual-schedule therapy and long-term results].

PMID- 11850877
TI  - Potentiation of the activity of mucosal vaccines by immunological adjuvants.

PMID- 11850878
TI  - Correlation between two DNA-based typing methods applied to Streptococcus
      pneumoniae strains: BOX-PCR assay as an alternative to ribotyping.
AB  - Seventy-nine Streptococcus pneumoniae isolates were characterized by ribotyping
      and BOX-PCR typing. The isolates comprised 14 most frequently identified
      serogroups and serotypes, 54 ribotypes (defined as each different combination of
      two DNA restriction fragment length polymorphism patterns obtained with HindIII
      and PvuII, respectively) and 51 BoxA-PCR patterns. There was close but not
      absolute correlation between molecular techniques. However, the discrimination
      indice of ribotyping--calculated on the basis of combination of the data obtained
      with both enzymes--equals that of BOX-PCR typing: D = 0.985 and the deduced
      genetic clustering of the pneumococcal strains was comparable.

PMID- 11850880
TI  - Income inequality and health.

PMID- 11850879
TI  - Screening of some Romanian plants for their activity against medically important
      insects.
AB  - The effects of the action of extracts from 82 plant species included in 39
      families of indigenous flora against the larvae and adults of house fly (Musca
      domestica), the mosquitoes (Aedes aegypti and Anopheles atroparvus) and the
      German cockroach (Blattella germanica) are presented. Some of the extracts were
      prepared from air-dried and ground plant material which was exhaustively
      extracted with successive solvents of different polarity: ethyl ether, ethyl
      alcohol and water. Other extracts were prepared either by distillation of the
      whole water extracts of 24 hours macerated plants or by water extraction from
      residues of plants remained after distillation. These plant extracts act as
      toxicants, growth and development and reproduction inhibitors and repellents. The
      differential responses induced by these plant extracts on assessed insects were
      influenced by several factors such as the plant species, the solvents used for
      extractions, the species and the stages of insect life and also the methods
      employed for evaluation. Some of the tested plants appear to have a great
      potential for providing safer insect control agents.

PMID- 11850881
TI  - Income inequality, social environment, and inequalities in health.

PMID- 11850883
TI  - Fighting Alzheimer's disease.

PMID- 11850882
TI  - Protecting genetic information.

PMID- 11850884
TI  - State public records privacy.

PMID- 11850886
TI  - Mental health needs of juvenile offenders.

PMID- 11850885
TI  - HIV testing of pregnant women and babies.

PMID- 11850887
TI  - Nuclear medicine.

PMID- 11850888
TI  - Obesity in America.

PMID- 11850889
TI  - Insurance information privacy.

PMID- 11850890
TI  - Women's health: coverage of services.

PMID- 11850891
TI  - Bioterrorism.

PMID- 11850892
TI  - The ADA at work.

PMID- 11850893
TI  - International trade of new agricultural products from biotechnology.

PMID- 11850894
TI  - Flavored cigarettes (bidis) popular among youth.

PMID- 11850895
TI  - Anti-inflammatory non-steroidal drug able to modulate IL-10 in allergic asthma.
AB  - Our studies target alternative/adjuvant therapies in allergic diseases, able to
      qualitatively/quantitatively modify cytokine profiles produced by both CD4+ T
      cell subsets (mainly Th1 and Th2) and B-cells, macrophages, etc. Current
      investigations aim to identify compounds capable to down-regulate IL-10 as an
      exponent of Th2 cell function and, consequently, to up-regulate Th1 cytokine
      levels. Experiments on ten allergic asthmatic patients and ten healthy subjects
      as control were performed. Cytokine production, triggered in PBMCs culture
      systems by PHA, was modulated with Indomethacin, a non-steroidal anti
      inflammatory drug and IL-10 was measured in 24 hours culture supernatants.
      According to our experimental data, IL-10 level of asthmatic patients' PBMCs in
      the resting state is not significantly different from control. PHA-activated
      PBMCs from asthmatic patients do not display significantly higher IL-10 levels
      than the normal subjects. The results obtained up-to-date reveal the fact that
      Indomethacin strongly down-regulates IL-10 levels in PBMCs cultures, in both
      asthmatic allergic patients and healthy subjects. It is obvious that the
      inhibitory effect of Indomethacin on IL-10 released by PBMCs is higher in the
      case of allergic asthmatic patients. The results obtained in this study
      demonstrate that Indomethacin is a possible therapeutic candidate in allergic
      asthma.

PMID- 11850897
TI  - Immunological approach in the diagnosis, therapy and prognosis of the exocrine
      pancreatic cancer.
AB  - The aim of the paper is to outline the most important up-to-date methods
      regarding the immunological approach in the diagnosis, treatment and prognosis of
      the exocrine pancreatic cancer, keeping in mind that this localisation of
      neoplastic disease represents the 5th cause of cancer-related death and
      especially, an important cause of morbidity. This disease, diagnosed in the past
      in later stages, being therefore associated with poor results, has turned to be
      characterized by increasing survival rates due to the improvements in diagnostic
      and therapeutic methods. Regarding the diagnosis strategy, progress was made in
      imagistic sphera, aiming: 1. an early diagnosis of pancreatic cancer and,
      implicitly, a high resectability rate of tumor, and 2. an evaluation of the
      timing for palliative therapeutic methods. So that, if in the past the diagnostic
      algorithm meant endoscopic retrograde-cholangio-pancreatography, computed
      tomography and angiography, at present it means nuclear magnetic resonance and
      helicoidal tomography. Concerning the treatment, it has to be multidisciplinary
      (surgery, radiotherapy, chemotherapy, immunotherapy), complex, because, after a
      resection for cure (R0), the main stay of the treatment, the mean survival at 5
      years is 3%-28% and the rate of recurrences is 33%-80%. Biological therapy
      (sometimes called immunotherapy, biotherapy or biological response modifier
      therapy) is a relatively new addition to the family of cancer treatments that
      also includes surgery, chemotherapy and radiation therapy. Biological therapies
      are designed to repair, stimulate or enhance the immune system responses. We
      shall try to point out how the exocrine pancreatic cancers, the same stages and
      undergoing the same approaches, have had different responses due to a different
      biological behavior and how the biological response modifiers (interferons,
      interleukins, colony-stimulating factors, monoclonal antibodies and vaccines) can
      improve the results in pancreatic cancer.

PMID- 11850896
TI  - Stimulation of mucosal immune response following oral administration of
      enterotoxigenic Escherichia coli fimbriae (CFA/I) entrapped in liposomes in
      conjunction with inactivated whole-cell Vibrio cholerae vaccine.
AB  - In this study, we have searched for an effective mucosal vaccine. An oral
      enterotoxigenic E. coli vaccine containing colonization factor antigen (CFA/I)
      associated with inactivated whole-cell V. cholerae vaccine (WCV) has been tested
      for safety and immunogenicity in animals. Five groups of animals were used. The
      results showed the following: (a) vaccine containing CFA/I antigen entrapped in
      liposomes and associated with WCV (batch C) had increased titers of specific
      antibodies to CFA/I antigen in 15 to 18 (83.3%) animals; (b) specific Peyer's
      patches (PP), lymph nodes (LN) and spleen (SPL) lymphocytes proliferation was
      detected following in vitro restimulation with CFA/I antigen or WCV. This
      response gradually increased to the highest value by the 35th postimmunization
      day. Moreover, lower PP, LN and spleen (SPL) proliferation was observed in
      rabbits receiving soluble CFA/I antigen (S-CFA/I) or free liposomes (F-L) alone;
      (c) adhesion of E. coli H10407 strain labelled with 3H-leucine in immunized and
      control animals revealed the following local effects: (i) protection of rabbit
      intestinal mucosa against virulent E. coli cells; (ii) inhibition of adhesion of
      ETEC bacteria to intestinal mucosa and (iii) significantly faster release of E.
      coli H 10407 strain labelled with 3H-leucine from the intestinal tract of
      immunized animals. The histopathological and electron microscope findings
      confirmed the above results. The experimental results point out an efficient
      protection against infection with E. coli strains (ETEC), after mucosal
      vaccination with CFA/I antigen entrapped in liposomes associated with inactivated
      whole-cell Vibrio cholerae as immunological adjuvant.

PMID- 11850898
TI  - Nature and prevalence of risk factors associated to type B and C acute viral
      hepatitis cases in Bucharest, 1998-2000.
AB  - The main objective of the study was to calculate and report the prevalence of
      probable risk factors involved in the transmission of pathogenic agents among
      type B and C acute viral hepatitis cases confirmed in Bucharest (1998-2000). The
      standardized values of the risks detected in the 45-180 days preceding the onset
      of illness suggest that in both types of acute viral hepatitis considered in our
      study transmission associated to the individuals' behaviour (19.0%-hepatitis B
      and 20.1%-hepatitis C) seems more frequent than "iatrogenic" transmission; in
      case of hepatitis B, sexual contacts with more than one partner coming first
      (15.7%), whilst in case of hepatitis C the use of i.v. drugs (heroine) was most
      frequently incriminated (12.4%). The study reviews the present knowledge of the
      risk factors involved in the transmission of the disease and approaches
      prevention strategies.

PMID- 11850899
TI  - The host of parasites--the ecological approach.
AB  - As in some studies the opinion that "the host is a biotope for the parasite,
      mediating its interactions with the environment" is a frequent occurrence, this
      paper is an attempt to point out the origin of this error and to present the
      theoretical basis for the accurate approach to these notions, namely parasite and
      host.

PMID- 11850900
TI  - Patient protection is a priority.

PMID- 11850901
TI  - Will mandated continuing education improve dentistry & at what cost?

PMID- 11850902
TI  - Aesthetic maxillofacial surgery, Part 1.

PMID- 11850903
TI  - Byte the bullet & exterminate the Y2K bug.

PMID- 11850904
TI  - Free consultation by state avoids occupational exposure, reduces costs.

PMID- 11850905
TI  - Doctors losing ground in battle as germs overpower antibiotics.

PMID- 11850906
TI  - A day in the mobile care dental clinic.

PMID- 11850907
TI  - Basic collection strategies.

PMID- 11850908
TI  - Simple solutions to difficult problems.
AB  - Difficult prosthetic problems can frequently be solved by applying simple
      solutions. Basic prosthetic techniques augmented with the dentist's ingenuity can
      help overcome many problems presented by patients facing difficult dental and
      personal financial situations. All cases presented have been in function for more
      than two years. All are functioning to the patients' satisfaction and none have
      presented significant maintenance problems. Compromises in health, function,
      comfort and esthetics can be minimized if the dentist is aware of all the
      available options.

PMID- 11850909
TI  - Quo vadis, dermatologia?

PMID- 11850910
TI  - Photobiology of lupus erythematosus.
AB  - Ultraviolet radiation in the 2850 to 3150 angstrom range can produce abnormal
      cutaneous reactions and exacerbation of systemic manifestations in some cases of
      subacute and acute systemic lupus erythematosus. It may also be responsible for
      cutaneous lesions and systemic involvement in rare cases of chronic discoid lupus
      erythematosus--probably those with disseminated lesions. The pathophysiological
      mechanism producing these photobiological effects in lupus erythematosus remains
      unknown.

PMID- 11850911
TI  - Psoriasis and Reiter's syndrome.
AB  - The possibility that psoriasis and Reiter's syndrome may be similar or closely
      related is illustrated by two cases in which (1) the initial illness was typical
      of Reiter's syndrome, (2) joint involvement resembled that of rheumatoid
      arthritis, and (3) the skin lesions, initially keratosis blennorrhagica, later
      became typical of psoriasis.

PMID- 11850912
TI  - Alopecia mucinosa and lymphoma. Report of two cases and review of literature.
AB  - A total of 90 cases of alopecia mucinosa (follicular mucinosis) have been
      reported in the world literature since Pinkus described the entity in 1957.
      Alopecia mucinosa appears morphologically in any variety of three basic clinical
      types: grouped folliculopapules, plaque forms of folliculopapules, and as boggy
      nodular masses. Characteristic histochemical changes of follicular mucinosis have
      been demonstrated in alopecia mucinosa as well as in selected cases of mycosis
      fungoides and lymphoma. The majority of case reports of alopecia mucinosa have
      been in children and young adults (58%), and the course of the dermatosis was
      usually uneventful. Beyond age 40, the disease appears to behave differently in
      that it follows a prolonged chronic course, and of 28 cases in this category four
      (15%) developed into either mycosis fungoides or lymphoblastoma.

PMID- 11850913
TI  - Allergy to lichens. Allergic contact dermatitis from usnic acid produced by
      lichenized fungi.
AB  - Two forest workers affected with allergic contact dermatitis, which occurred only
      during work in forest areas, showed positive patch test reactions to lichens
      containing usnic acid and to isolated usnic acid. Lichens are plants composed of
      fungi living in symbiosis with algae. Usnic acid, one of the lichenic acids which
      accumulates in lichenized fungi, is a monobasic acid with dibenzofuran structure
      and antibiotic properties. Dibenzofuran is chemically related to furocoumarans.
      Lichens are plentiful in temperate zone forests and allergy to usnic acid
      represents some part of the "cedar-poisoning" problem in British Columbia.
      Geographical distribution of lichens containing usnic acid suggests that allergy
      to usnic acid will be found to be more common than presently recognized.

PMID- 11850914
TI  - Basophil degranulation induced by oral poison ivy antigen.
AB  - Seven subjects shown by patch test to be sensitive to poison ivy oleoresin were
      challenged with graded oral doses of ivy extract. In each instance the
      circulating basophil leukocytes showed significant degranulation within one hour
      of challenge. This finding was interpreted as evidence of the presence of
      immediate-type circulating antibody to ivy antigen in these subjects. No drop in
      the absolute basophil count was noted, but with higher oral doses the
      degranulation persisted for several days. Thirteen control subjects showed no
      change in the basophil morphology or count, indicating that the resin at these
      levels was not toxic to this cell. All but one of the sensitive subjects showed
      objective patch test evidence of hyposensitization following the intensive three
      week course of oral poison ivy antigen.

PMID- 11850915
TI  - Pitted keratolysis.
AB  - Pitted keratolysis is a superficial infection of the skin confined to the stratum
      corneum. The causative organism has not been identified. The clinical syndrome is
      distinct and is characterized by pits and superficial erosions in the pressure
      areas of the soles and in the lateral surfaces of the toes. The histopathology of
      the lesions is presented and world literature is reviewed. It is concluded that
      this disease is not limited to the tropical climates, although cases tend to be
      more severe in these areas.

PMID- 11850916
TI  - Cutaneous North American blastomycosis and black dots.
AB  - The presence of black dots may be an aid in the diagnosis of blastomycosis of the
      skin. Degeneration of papillary blood vessels leads to extravasation of red blood
      cells. The cells are found in the dermis and between epidermal cells.

PMID- 11850917
TI  - Unusual cutaneous findings in primary systemic amyloidosis. Report of a case.
AB  - A case of primary, systemic amyloidosis is reported because of the unique
      location of cutaneous lesions. Amyloid deposits had occluded both external
      auditory canals. Both the cutaneous biopsies and postmortem examination
      established the diagnosis.

PMID- 11850918
TI  - Livedo reticularis in association with acute lymphocytic leukemia. Report of a
      case.
AB  - A case of livedo reticularis of relatively short duration associated with severe
      pain in the legs is presented. The skin condition preceded the onset of a
      fulminant and fatal acute lymphocytic leukemia in this patient by a period of
      fourteen months.

PMID- 11850919
TI  - Multiple cutaneous and conjunctival keratoacanthomata.
AB  - A case of multiple keratoacanthomata affecting both the skin and conjunctiva is
      reported. Although the patient was carefully studied on several occasions, the
      correct diagnosis was long delayed for the following reasons: (1) a history of
      pulmonary tuberculosis, (2) the disparity between the microscopic findings in
      solitary keratoacanthoma and those in some cases of multiple keratoacanthomata,
      (3) the unusual and heretofore unreported coexistence of cutaneous and
      conjunctival lesions.

PMID- 11850920
TI  - Bullous dyskeratosis follicularis and acrokeratosis verruciformis. Report of a
      case.
AB  - Morbus Darier, Hailey's familiar benign chronic pemphigus, and acrokeratosis
      verruciformis were observed in one patient. The diagnosis was based on the
      clinical picture and microscopic studies. The simultaneous occurrence in one
      patient of these congenital diseases suggests that it is possible that all three
      disorders are variants of one and the same disease. Five close relatives of the
      patient had acrokeratosis verruciformis.

PMID- 11850921
TI  - Subcorneal pustular dermatosis. A follicular variant?
AB  - A middle-aged woman repeatedly developed crops of small pustules on the face, the
      trunk, and the upper arms without any general symptoms. Histological examinations
      revealed subcorneal pustules in the upper parts of the hair follicles. It is
      considered that this case may be a follicular variant of subcorneal pustular
      dermatosis.

PMID- 11850922
TI  - Symmetric acroleukopathy in mother and daughter.
AB  - Simultaneous occurrence of congenital symmetric acroleukopathy in a Japanese
      mother and her daughter is reported. A biopsy specimen taken from one of the
      mother's lesions showed dopa-negative melanocytes.

PMID- 11850923
TI  - Pituitary-adrenal function following topical triamcinolone acetonide and
      occlusion.
AB  - This study was undertaken to investigate the possible pituitary-adrenal
      suppressive effects of triamcinolone acetonide under occlusive dressings in six
      psoriatic patients. Forty-five grams of a cream containing 0.1% triamcinolone
      acetonide was applied daily to the psoriatic lesions of four patients and covered
      with an occlusive dressing. Two patients received daily applications of 45 gm of
      0.01% triamcinolone acetonide cream and occlusive dressings. The four patients
      who received the 0.1% triamcinolone acetonide applications showed a marked
      decrease in the 24-hour urinary 17-hydroxycorticosteroids and no significant
      response to intravenous metyrapone testing. The two patients who were treated
      with 0.01% triamcinolone acetonide also showed a significant decrease in 24-hour
      urinary 17-hydroxycorticosteroids, but a partial response to metyrapone testing.
      Percutaneous absorption of as little as 1 to 2 mg of triamcinolone acetonide may
      affect pituitary-adrenal function.

PMID- 11850924
TI  - Avascular bone necrosis. A complication of long-term corticosteroid therapy.
AB  - A patient with pemphigus vulgaris, treated with long term corticosteroids,
      developed avascular necrosis of the head of the femur and humerus, bilaterally.
      This patient emphasizes the fact that the use of corticosteroids in dermatologic
      disorders may be a predisposing cause in avascular necrosis, and that this is
      another side effect of long-term corticosteroid therapy. This patient is
      particularly remarkable in that both hips and both shoulders were involved.

PMID- 11850926
TI  - Fixed drug eruption: ethchlorvynol. Report of a case.

PMID- 11850925
TI  - Myotonia and keratoderma induced by 20,25 diazacholestenol.
AB  - A new inhibitor of cholesterol synthesis, 20,25 diazachlestenol, produced
      myotonia in 31 persons; and, in six of these, a keratoderma which resembles the
      natural disease, keratoderma climactericum. These observations further emphasize
      the importance of normal lipid synthesis in orderly cornification.

PMID- 11850927
TI  - Liquid-nitrogen neuropathy.
AB  - Neuropathy due to liquid-nitrogen cryotherapy of skin lesions is reported. The
      anatomic basis for this untoward occurrence is depicted. Precautions to avoid
      neuropathy are enumerated.

PMID- 11850928
TI  - Zirconium granuloma following treatment of rhus dermatitis.
AB  - Zirconium granuloma of the skin, initially seen following the use of zirconium
      deodorants, continues to occur secondary to the treatment of plant dermatitis
      with compounds containing zirconium. In our patient the reaction appeared eight
      weeks after initial use of the agent and has persisted for 18 months without
      therapy. Intradermal injection of minute amounts of a soluble zirconium compound
      resulted in production of a lesion that was identical clinically and
      histologically with the primary lesion at the end of four weeks. Although this
      disorder involves the skin primarily, the slight elevation in gamma-globulin
      level observed may be a reflection of its systemic pathogenesis.

PMID- 11850929
TI  - Effect of systemically administered epinephrine on palmar sweating.
AB  - We have described our experience with a modified Bullard sudorometer for the
      continuous recording of sweating rates from selected skin areas. This involves an
      electrical system for sensing water vapor pressure and expressing it as relative
      humidity. This sensitive device was used to study the effect of systemically
      administered epinephrine on palmar sweating. Thirty-three young adults were
      tested; ten demonstrated a decrease after epinephrine administration. Those
      subjects demonstrating a decrease in palmar sweating were from the group of
      subjects who perspired heavily. The possible mechanisms for this are discussed.

PMID- 11850930
TI  - Chromosome studies of normal and psoriatic skin fibroblasts.
AB  - A method for obtaining large numbers of fibroblasts from punch biopsies of skin
      tissue and a procedure for the visualization of chromosomes from these cells are
      presented in detail. The chromosomes are well separated, and fine details of
      their structure are seen. A study was made of 275 cells from apparently normal
      and from involved areas of skin from patients with psoriasis. No changes either
      in the number or in the fine structure of the chromosomes were observed.

PMID- 11850931
TI  - Recent advances in the understanding of the penicillin urticarias.
AB  - The three major groups of immunoglobulins (gamma G, gamma A, and gamma M)
      associated with this disease are reviewed. The presence or absence of atopic
      disease may account for percentage variability of gamma A because reagins (skin
      sensitizing antibodies) are found in this immunoglobulin. The gamma A is the
      antibody usually responsible for anaphylaxis, rather than the gamma G
      precipitins, so stressed in the past. All three immunoglobulins may be found in
      serum sickness, which could account for the complex nature of this type of
      penicillin urticaria. The merits of the immunological tests (penicilloyl
      polylysine, benzyl penicillin, hemagglutination, basophil degranulation) for the
      detection of penicillin sensitivity are analyzed, particularly as each applies to
      the various types of penicillin urticaria (serum sickness, anaphylactic,
      dermographic, delayed dermographic, and simple chronic urticaria and the lupus
      diathesis). The penicilloyl-polylysine test is greatly overrated as a means of
      predicting possible anaphylaxis. The benzyl penicillin skin test properly
      performed is an excellent means of indicating this.

PMID- 11850932
TI  - Pigmentation.

PMID- 11850933
TI  - Pulmonary hypertension. Raynaud's disease, telangiectasias.

PMID- 11850934
TI  - Morquio's syndrome?

PMID- 11850935
TI  - Diffuse leukoderma following use of monobenzone.

PMID- 11850936
TI  - Genetic classification of ichthyosis.
AB  - Ichthyosis has been classified on a genetic basis. Four varieties--ichthyosiform
      erythroderma, lamellar ichthyosis, Refsum's syndrome and the Sjogren-Larsson
      syndrome--are inherited as autosomal recessive traits. One type is inherited as a
      sex-linked recessive trait while another variety of ichthyosis (with or without
      atopy), bullous ichthyosiform erythroderma, and very rarely ichthyosis hystrix
      are due to autosomal dominant genes.

PMID- 11850937
TI  - "Brush" technique in animals. Finding contact sources of fungus diseases.
AB  - A technique is described for collecting specimens of hairs and scales from
      animals by means of a brush to help in the diagnosis of fungus diseases. The
      brush is then used to implant such materials on special culture media for the
      growth and identification of fungus organisms. This method offers a better chance
      to find fungus organisms than the previous method of plucking, which was like
      looking for a needle in a haystack. The special media makes possible the rapid
      diagnosis of the presence of pathogenic fungi.

PMID- 11850938
TI  - Kaposi's idiopathic hemorrhagic sarcoma.

PMID- 11850939
TI  - Dermopathy in diabetes mellitus.

PMID- 11850940
TI  - Scleredema adultorum.

PMID- 11850941
TI  - Porphyria.

PMID- 11850942
TI  - Primary amyloidosis (and plasma cell dyscrasia).

PMID- 11850943
TI  - Dysproteinemic purpura.

PMID- 11850944
TI  - Steatocystoma Multiplex.

PMID- 11850945
TI  - Necrobiosis lipoidica.

PMID- 11850946
TI  - Linear verrucous nevus.

PMID- 11850947
TI  - Subacute lupus erythematosus, rheumatic valvular heart disease, urinary tract
      infection.

PMID- 11850948
TI  - Broad spectrum of leukoderma acquisitum centrifugum.
AB  - A series of diverse neuroectodermally derived tumors associated with halos of
      leukoderma is presented. Clinically these lesions have in common a centrally
      placed, usually pigmented tumor encircled by a zone of hypopigmentation. The
      histological findings include (1) reduction or absence of epidermal melanin, but
      persistence of amelanotic melanocytes in the leukodermic halo; (2) a variety of
      tumors including nevus-cell nevus, neuroid nevus, blue nevus, neurofibroma, and
      malignant melanoma; (3) variable numbers of "small dark cells" whose nature is
      unclear, and which probably represent in part small nevus cells and in part
      lymphoid cells; and (4) damage to some tumor cells which presumably could be the
      cause of their destruction. Also presented are histochemical demonstrations of
      tyrosinase activity and immunohistochemical studies for presence of gamma
      globulin in the tumors. Using the fluorescent antibody technique it was not
      possible to show gamma-globulins in patients' sera directed against their tumors.
      The relationship of developing hypopigmentation to the spontaneous regression of
      cutaneous neuroectodermally derived tumors is discussed.

PMID- 11850949
TI  - Pruritus, an uncommon but important symptom of systemic carcinoma.
AB  - A distinctive pruritic syndrome associated with systemic cancer is described.
      Prolonged, variably severe pruritus with a tendency to localization on the legs,
      upper trunk, and extensor surfaces of the upper extremities is the presenting
      symptom. Patients with unexplained persistent itching as herein described should
      be investigated for a hidden malignancy. The persistence or recurrence of
      itching, months or even years after apparent cure of a systemic carcinoma,
      suggests that destruction or removal of the primary tumor was incomplete, or that
      metastasis has supervened. A small carcinomatous focus may exist for many months
      and at times for years before clinical recognition is possible with diagnostic
      methods currently available.

PMID- 11850950
TI  - Granulomatous cheilitis.
AB  - Four cases of granulomatous cheilitis, an uncommon disease and one that is
      difficult to treat, are described. The cause of chronic swelling of the lips has
      been in dispute for over 50 years. In our material we have excluded sarcoidosis
      and silica, two of the postulated causes, and we suggest that hypersensitivity is
      concerned.

PMID- 11850951
TI  - Stomatitis, dermatitis, and denture materials.
AB  - Denture base materials of the past and present are reviewed. Hypersensitivity
      stomatitis venenata is an uncommon cause of "denture sore mouth." Four cases are
      cited in evidence that acrylic dentures, even when heat cured, can produce a
      hypersensitivity type of stomatitis venenata. The management of acrylic
      hypersensitivity by the substitution of polystyrene as a denture base material is
      recommended.

PMID- 11850952
TI  - Confluent and reticulated papillomatosis of Gougerot and Carteaud.
AB  - Confluent and reticulated papillomatosis is a rarely reported dermatosis of
      unknown origin. It is similar to nummular and confluent papillomatosis; punctate,
      pigmented verrucose papillomatosis; acanthosis nigricans; pseudoacanthosis
      nigricans; benign acanthosis nigricans; pseudoatrophoderma colli; tinea
      versicolor; Darier's disease; epidermodysplasia verruciformis; and verruca plana.
      Treatment may be temporarily successful, but the lesions usually recur within a
      period of months.

PMID- 11850953
TI  - Necrosis in leg ulcers. Probable role of fluocinolone acetonide.
AB  - Necrosis in chronic leg ulcers developed in all of the four patients who were
      treated topically with a fluocinolone acetonide-neomycin sulfate ointment. This
      was probably due to the vasoconstrictive properties of the steroid. A warning
      against the topical use of potent steroids in skin diseases with impaired
      circulation seems to be justified.

PMID- 11850954
TI  - Unusual familial hypopigmentary anomaly.
AB  - A hitherto unreported bilateral and symmetrical hypopigmentary anomaly is
      reported in five members of a Negro family. The pattern of inheritance would
      appear to be autosomal dominant and it is concluded that this is a benign
      pigmentary alteration unrelated to underlying disease.

PMID- 11850955
TI  - Ingram method of treating psoriasis.
AB  - A method of treating psoriasis without the use of corticosteroids or antimitotic
      agents is described. A special technique incorporating the use of anthralin is
      employed with results which are better than any so far published. As well as
      being effective and inexpensive, the technique is safe, with no systemic side
      effects. It has been adopted as the standard therapeutic procedure in a number of
      centers in England and Europe.

PMID- 11850956
TI  - Effect of thiabendazole on Ancylostoma caninum.
AB  - Thiabendazole inhibits nematode development before the third stage is reached.
      The minimum effective concentration is 0.1 microgram/ml during the first 48 hours
      of development and 1.0 microgram/ml at 72 hours of development. The drug has no
      effect on the third stage but is again effective on larvae that have undergone 72
      hours of development in the intestine of the specific host (dog). Increasing
      concentrations of the drug seem to be necessary to kill the larvae as the
      organism progresses in development. Concentrations of the drug that kill the
      organism before it enters the third stage (infective form) are exceeded in the
      blood and skin of sheep by a single 50 mg/kg oral dose. It is speculated that the
      drug is not effective against the infective stage because it does not enter the
      larvae and that the larvae progress in the skin of man to a stage where they
      ingest the drug or become permeable to it.

PMID- 11850957
TI  - Leukoderma acquisitum centrifugum. An unusual case.
AB  - A case is presented of a 9-year-old girl who developed a depigmented halo around
      a pigmented tumor of the skin on her shoulder. She also developed widespread
      metastases in the ipsilateral axillary lymph nodes, lungs, and, presumably,
      liver, and subsequently died of her disease. Histologic interpretations of the
      nature of the cutaneous tumor and axillary metastases are given and the
      suggestion made that the skin lesion was a malignant melanoma. Should this
      interpretation be correct, this case represents the first of its kind in which a
      lesion in a child with the clinical features of a halo nevus proved to be a fatal
      malignant melanoma.

PMID- 11850959
TI  - Ultraviolet-induced acantholysis in pemphigus.
AB  - Ultraviolet irradiation produced an acantholytic phenomenon in normal skin of
      seven patients with pemphigus foliaceus. In six of the seven patients, this
      reaction was manifested by a positive Nikolsky sign and was confirmed by biopsy
      in four. Friction alone, infrared irradiation, occlusive dressing, and a
      rubefacient failed to produce a similar reaction. The thermal burn in the skin of
      patients having pemphigus was of subepidermal type. Ultraviolet-induced
      acantholysis was inhibited by chloroquine phosphate, taken orally, in the two
      patients tested. Prednisone had no such effect. It is concluded that ultraviolet
      light is a major aggravating stimulus for pemphigus foliaceus.

PMID- 11850958
TI  - Malignant melanoma arising from an intradermal nevus.
AB  - A case of malignant melanoma apparently arising from the lower portion of a
      preexisting intradermal hairy nevus is presented. This case is an exception to
      the general rule that if malignant melanomas arise from nevi they originate in
      nevi with a junctional component.

PMID- 11850960
TI  - Bronchial carcinoid tumor with skin metastases.
AB  - The occurrence of multiple dermal and subcutaneous nodules and tumors as a
      significant sign in a case of a metastatic bronchial carcinoid is reported. The
      clinical manifestations of bronchial carcinoid often differ from those associated
      with the more common malignant carcinoids of the intestinal tract. It is possible
      that these differences might be due to an enzymatic defect in the bronchial
      carcinoid tumors.

PMID- 11850961
TI  - Sensitivity to topically applied vitamin E.
AB  - A search of the literature has not revealed any reports of allergic eczematous
      contact dermatitis due to the topical application of vitamin E. A case of contact
      allergy to synthetically produced alpha-tocopherol is herein reported. It is felt
      that this is a rare event in view of the fact that this vitamin is widely used
      topically in this country and abroad.

PMID- 11850962
TI  - Granuloma faciale with lesions on the face and hand.
AB  - A patient with granuloma faciale had multiple lesions on the face and one lesion
      on the dorsal surface of one hand. This case adds a clinical parallel to the
      recognized histological parallel between granuloma faciale and erythema elevatum
      diutinum.

PMID- 11850963
TI  - Fine structure of the nevus cell.
AB  - The purpose of this investigation was to characterize the fine structure of the
      nevus cell and to demonstrate, if possible, a unique premelanin granule. The
      presence of this granule in the nevus cell would substantiate the relationship
      between the nevus cell and the melanocyte. Biopsy specimens of dermal nevi with
      and without ultraviolet light stimulation were studied with an electron
      microscope and the following conclusions were reached: (1) The fine structure of
      the nevus cell is comparable to that of the melanocyte. (2) The premelanin
      granule or melanosome is present in the nevus cell, particularly after prolonged
      ultraviolet light stimulation. (3) The nevus cell is probably an embryonal cell
      that can differentiate with appropriate stimuli.

PMID- 11850964
TI  - Levels of antibody to Staphylococcus epidermidis in patients with acne vulgaris.
AB  - Sera from 23 patients with acne vulgaris of varying degrees and sera from 15
      patients with skin diseases other than acne were tested for antibody levels to
      Staphylococcus epidermidis by use of bacterial agglutination and agar-gel
      immunodiffusion. Antibody levels to S epidermidis varied from 0 to 1:160 in both
      the patients with acne and in the control groups. There was no correlation
      between the antibody level to S epidermidis and the degree of acne. In a previous
      investigation it was found that antibody levels to Corynebacterium acnes are
      significantly increased in serum from patients with papulopustular and cystic
      acne. Both S epidermidis and C acnes can frequently be isolated from lesions in
      acne. The fact that antibody levels are increased to C acnes but not to S
      epidermidis may indicate that the mere presence of an organism in the acne lesion
      is not sufficient stimulation for antibody formation. The increase of antibody to
      C acnes which was demonstrated previously in patients with severe acne vulgaris
      may therefore reflect a direct involvement of the organism in the acne process.

PMID- 11850965
TI  - Mitotic rates of rat epidermis. During growth, maturity, senility, and
      regeneration.
AB  - Adult epidermal tissues are renewing cell populations. Mitosis continuously
      provides new cells replacing those that became keratinized and ultimately shed.
      It seems plausible to assume that in the epidermis of growing individuals mitosis
      supplies cells both for cell addition (growth) and renewal. During growth, more
      cells are presumably retained in the tissue than become lost through
      desquamation. It is feasible by cutaneous incision to temporarily revert adult
      epidermis into a growing cell population. Presumably also during healing, cell
      production exceeds cell loss. What is the magnitude of cell production for
      renewal of adult epidermis, for simultaneous cell addition and renewal during
      growth, as well as during epidermal regeneration? To elucidate these problems,
      the mitotic rates of three epidermal cell populations (ear, plantar, and
      abdominal epidermis) were determined in the growing, adult, and senile rat.
      Further, the adult ear and back skin epidermis was converted by cutaneous
      incision into regenerating cell populations, and the mitotic rates were
      determined during healing at intervals from six hours to nine days.

PMID- 11850966
TI  - Cisplatin induces acute renal failure by impairing antioxidant system in guinea
      pigs: effects of antioxidant supplementation on the cisplatin nephrotoxicity.
AB  - This study aims to investigate the role of oxidants in cisplatin-induced
      nephrotoxicity. Cisplatin was administered intraperitoneally (i.p.) in a single
      dose (5 mg/kg) and guinea pigs were killed either after 24 h or 7 days. The same
      experiment was performed using animals treated with vitamins C and E combination
      and a natural antioxidant extract (SARMEX). The kidneys were then removed to be
      used in the analyses. Blood samples were also obtained from the animals to be
      used in routine biochemical assays. Twenty-four hours after treatment there was a
      significant decrease in the renal activities of total superoxide scavenger
      activity (TSSA), superoxide dismutase (SOD) and catalase (CAT) accompanied by a
      rise in malondialdehyde (MDA) levels. After 7 days, the fall in kidney enzymatic
      activities was far greater, while the increase in blood urea (BUN) and creatinine
      (CRE) was marked. Treatment with antioxidants causes significant increases in
      renal TSSA (7 day), non-enzymatic superoxide scavenger activity (NSSA) (24 h and
      7 day) and SOD (7 day) activities, does not change glutathione peroxidase (GSH
      Px) activity and decreases renal MDA (24 h and 7 day), blood BUN (7 day) and CRE
      (7 day) levels. Our results suggest that cisplatin treatment impairs both
      enzymatic and non-enzymatic antioxidant systems and causes peroxidation in the
      renal tissue, which leads to kidney failure. Antioxidant supplementation
      strengthens the renal antioxidant system, eliminates oxidation reactions, and
      prevents cisplatin-induced kidney failure.

PMID- 11850967
TI  - An oral (gavage) control embryo-fetal development study in the Wistar Hannover
      rat.
AB  - Many of the studies conducted to examine the developmental and reproductive
      toxicity potential of candidate pharmaceuticals use the Sprague-Dawley rat as the
      animal model. This is due in part to the large database for this outbred rat
      available for comparison of litter data, and the low incidence of fetal
      malformations and variations. The following study was conducted to generate
      information on potential embryo-fetal developmental defects and litter data in
      another outbred stock of rat, the Wistar Hannover. One hundred fifty pregnant
      female Wistar Hannover rats (Tac:Glx:WIfBR) were dosed orally once per day with
      distilled water from Gestation Days (GD) 6 through 17 covering the time from
      implantation to closure of the hard palate (GD0 = day of insemination). Caesarean
      sections were performed on Day 20 of gestation. All fetuses were examined for
      external, visceral and skeletal malformations and variations. Macroscopic and
      histomorphologic examinations were also completed for the F0 females at
      termination. The percent pregnant (88%) and litter size (average 10.6) were found
      to be lower than that commonly reported for the Sprague-Dawley rat (Crl:CD
      (SD)BR; 95.4% and 14.6, respectively). Pre-implantation loss (14.1%), post
      implantation loss (7.4%) and percent resorptions (7.2%) occurred at a higher
      incidence than typically seen in the Sprague-Dawley rat (5.9, 5.6 and 5.1%,
      respectively). The average fetal body weights for both the female and male rats
      were lower than those typically seen in the Sprague-Dawley rat. External,
      visceral and skeletal examination of the F1 fetuses revealed numerous
      malformations and variations which also occurred at higher incidences than those
      reported for the Sprague-Dawley rat. Routine macroscopic and histomorphologic
      examination showed there were no changes that would be interpreted to have
      impaired mating performance, fertility or gestation. Thus, this study provides
      information on the reproductive effects and the background incidence of embryo
      fetal development defects that could be used for comparison to those identified
      when using this outbred rat for developmental and reproductive toxicity studies,
      as well as for comparison to the more commonly used rat stock, the Sprague-Dawley
      rat. For the parameters evaluated, the Wistar Hannover rat had greater
      variability and an increased incidence of spontaneous malformations as compared
      to the Crl:CD (SD)BR Sprague-Dawley rat. These findings should be considered if
      this stock of rat is selected in the conduct of developmental and reproductive
      toxicity studies.

PMID- 11850968
TI  - Effect of alachlor on hepatic cytochrome P450 enzymes in rats.
AB  - Alachlor ((2-chloro-N-methoxymethyl)-N-(2,6-diethylphenyl)acetamide) is a widely
      used preemergence herbicide which has been classified by the USEPA as a probable
      human carcinogen. The herbicide has been suggested to be metabolized by hepatic
      cytochrome P450 system. We examined the effects of alachlor on cytochrome P450
      enzymes in rat liver microsomes. Rats were treated intraperitoneally with
      alachlor daily for 5 days, at doses of 25, 50 and 100 mg/kg. Among the cytochrome
      P450-dependent monooxygenase activities, 7-pentoxyresorufin O-depentylase, which
      is associated with CYP2B1, was dose-dependently increased by alachlor. The
      induction relative to control activity was 1.7-4.2-fold. The activities of CYP1A
      dependent monooxygenases such as 7-ethoxy-resorufin O-deethylase and acetanilide
      4-hydroxylase were also significantly increased by alachlor at doses of 50 and
      100 mg/kg (1.7-2.1-fold). Furthermore, immunoblotting showed that alachlor
      significantly increased CYP2B1/2 and CYP1A1/2 protein levels by 4.2-6.3- and 1.8
      fold, respectively. Although 7-ethoxycoumarin O-deethylase, bufuralol 1'
      hydroxylase and 4-nitrophenol 2-hydroxylase activities were significantly
      increased by alachlor at higher doses (> or = 50 mg/kg), the induction ratios
      were less than 1.6-fold. The activities of other cytochrome P450-dependent
      monooxygenases, namely testosterone 7 alpha-hydroxylase, testosterone 2 alpha
      hydroxylase, testosterone 6 beta-hydroxylase and lauric acid omega-hydroxylase,
      were not affected by alachlor at any dose. In addition, there was no significant
      change in the protein levels of CYP2C11/6, CYP2D1, CYP2E1, CYP3A2/1 and
      CYP4A1/2/3. These results suggest that alachlor selectively induces cytochrome
      P450 isoforms of the CYP1A and CYP2B subfamilies in rat liver microsomes, and
      that the expression of these isoforms is closely related to the toxicity of
      alachlor.

PMID- 11850970
TI  - Detection of DNA damage in mouse peripheral blood leukocytes by the comet assay
      after oral administration of monocrotophos.
AB  - The objective of this study was to determine if single/double strand DNA breaks
      could be induced by monocrotophos (organophosphorus pesticide) in mice in vivo
      using the comet assay. Mice were dosed orally with 0.046, 0.093, 0.186, 0.373 and
      0.746 mg/kg body weight of monocrotophos, and the assay was performed on whole
      blood after 24, 48 and 72 h. A significant increase in mean comet tail length
      indicating DNA damage was observed at 24 and 48 h post-treatment with
      monocrotophos when compared to controls. A decrease in the mean tail length was
      observed at 72 h post-treatment indicating repair of the damaged DNA. The mean
      tail length showed a dose-related increase and time dependent decrease. The study
      reveals that comet assay is a sensitive and rapid method to detect genotoxicity
      of monocrotophos.

PMID- 11850971
TI  - Cytotoxicity of estradiol, equilin, equilenin, and their derivatives on Chinese
      hamster V79 cells.
AB  - Recently, we investigated the inhibitory effects of 17 beta-estradiol and
      diethylstilbestrol on microtubule assembly, cytotoxicity, and aneuploidy in V79
      cells. The present study analyzes the effects of equilin and equilenin (amongst
      the natural estrogens originally isolated from the urine of pregnant horses) and
      their related compounds, on the relative plating efficiency of Chinese hamster
      V79 cells. The results showed that a hydroxyl group on 17-C and a methoxyl group
      on 3-C of the estrogen skeleton were important for cytotoxicity. Of the various
      compounds analyzed, 2-methoxyestradiol had the strongest cytotoxicity, suggesting
      also the importance of a methoxyl group on 2-C.

PMID- 11850969
TI  - A correlative study on antimutagenic and chemopreventive activity of Acacia
      auriculiformis A. Cunn. and Acacia nilotica (L.) Willd. Ex Del.
AB  - The present study provides a correlation of the antimutagenic and chemopreventive
      activity of the barks of two commonly observed plants viz. Acacia auriculiformis
      and Acacia nilotica. We used the Ames antimutagenicity assay and the mouse
      mammary gland organ culture (MMOC) model. The plants were extracted with organic
      solvents to obtain chloroform fractions and acetone extracts. The antimutagenic
      activity was determined in two different strains using both direct-acting [4
      nitro-o-phenylenediamine (NPD) or sodium azide] and indirect-acting [2
      aminofluorene (2AF)] mutagens. The anticarcinogenic activity was evaluated based
      on the development of preneoplastic lesions in response to the chemical
      carcinogen 7,12-dimethylbenz[a]anthracene (DMBA). The results showed that the
      activity resulting from the 2AF mutagen was selectively greater than the activity
      from the direct-acting mutagens. Moreover, in general, acetone extracts were more
      potent in suppressing mutagenesis than the chloroform extracts. The
      antimutagenicity results obtained with extracts using the 2AF--TA100 system were
      comparable to the chemopreventive results with DMBA-induced mammary lesions. The
      order of activity in both tests was A. nilotica > A. auriculiformis. These
      results exhibited a good correlation between the antimutagenesis assay and the
      MMOC model, suggesting that these plants may contain active chemopreventive
      agents.

PMID- 11850972
TI  - In vitro permeability and binding of hydrocarbons in pig ear and human abdominal
      skin.
AB  - Human skin has continual exposure to chemicals due to various occupational
      activities. Chemicals that get on skin have the potential to be absorbed. Hence,
      the potential human health hazards of a chemical must include an estimate for
      percutaneous absorption. An inexpensive, easy, and adequate model for the
      quantitative measurement of skin penetration of chemicals from JP-8 is absent.
      Cutaneous penetration studies in vitro through human skin are severely limited
      due to the lack of availability of the human skin. In this study, we have shown
      that pig ear skin can be used as a model for risk assessment from the
      percutaneous absorption of chemicals. We determined flux and permeability
      coefficient (Kp) of three chemicals--heptane, hexadecane, and xylene--from their
      permeation profile through porcine and human skin. Binding of these chemicals to
      porcine stratum corneum (SC) and human SC were also determined. Factors of
      difference (FOD) in the permeability of pig and human skin were 1.71, 1.28, and
      1.16, respectively, for heptane, hexadecane, and xylene. FOD in binding of
      heptane, hexadecane, and xylene to pig and human SC were found to be 1.04, 0.76,
      and 1.31, respectively. Since, FOD for permeability and binding parameters were
      less than 2, hence, we conclude that pig ear skin can be used as model for humans
      for risk assessment from percutaneous absorption of chemicals.

PMID- 11850973
TI  - Effects of chronic administration of huperzine A on memory in guinea pigs.
AB  - Effects of subchronic administration of huperzine A, a cholinesterase inhibitor,
      on spatial memory were studied in guinea pig. Spatial memory was appreciated by
      the Morris water maze test. At a dose of 0.25 microgram/h, inhibiting 36% of
      blood AChE and 14-20% of central AChE, no effect on spatial learning was found.
      At a dose of 1 microgram/h, inhibiting 20% of blood AChE and 14-20% of central
      AChE, no memory impairment was found, on the other hand, a memory enhancing
      effect, limited to the first day was shown. It thus appears that subchronic
      administration of huperzine A did not induce deleterious effects on spatial
      memory.

PMID- 11850974
TI  - Lack of DNA binding in the rat nasal mucosa and other tissues of the nasal
      toxicants roflumilast, a phosphodiesterase 4 inhibitor, and a metabolite, 4-amino
      3,5-dichloropyridine, in contrast to the nasal carcinogen 2,6-dimethylaniline.
AB  - The phosphodiesterase 4 inhibitor Roflumilast (B9302-107) (RF) and its metabolite
      4-amino-3,5-dichloropyridine (ADCP) produced nasal toxicity in preclinical safety
      studies with rats. The purpose of this study was to assess the possible formation
      of DNA adducts, by RF and ADCP, in the nasal mucosa, liver and testes of male
      rats using the 32P-postlabeling assay. For comparison, rats were exposed to the
      DNA-reactive carcinogens 2,6-dimethylaniline (DMA), also known as 2,6-xylidine, a
      nasal carcinogen, and the aromatic amine carcinogens 4,4'-methylene-bis(2
      chloroaniline) (MOCA), which yields monocyclic DNA adducts, and 2
      acetylaminofluorene (2-AAF). In the case of RF, possible sources of DNA adducts
      include the parent molecule and its ADCP moiety by enzymatic N-hydroxylation and
      sulfation, reactions typical of carcinogenic aromatic amines. 4-Acetoxylamino-3,5
      dichloropyridine (N-acetoxy-ADCP), a chemically activated derivative of ADCP, was
      prepared and used to modify DNA which was then used to establish the
      chromatographic conditions with which to reliably detect whether or not such
      adducts were formed metabolically from RF and ADCP. Similarly, a standard N
      hydroxy-DMA was prepared, but the corresponding N-acetoxy derivative was unstable
      and decomposed during synthesis. Both N-hydroxy-DMA and N-acetoxy-ADCP were
      mutagenic in the Salmonella typhimurium Ames assay using strain TA100 without an
      exogenous bioactivation system, with the former being more potent. N-hydroxy-ADCP
      was essentially inactive in this assay. For the 32P-postlabeling assay, male
      Wistar rats were exposed to the test substances and carrier control compounds by
      intragastric instillation at the selected dose levels for 7 days. Subsequently,
      the nasal mucosa, liver, and testes of the rats exposed to the test or control
      compounds were extirpated, the DNA extracted and the samples postlabeled. The
      patterns of adducts formed with the test compounds were compared to those formed
      in N-acetoxy-ADCP- and N-hydroxy-DMA-adducted DNA, which were assayed by both
      nuclease P1 and butanol enhancement methods. Based upon the similarity of results
      from the two enhancement methods, only the former was used for the in vivo
      studies. No evidence was obtained for the formation of DNA adducts from RF or its
      metabolites, specifically ADCP, under the conditions of these assays despite the
      ability to detect adducts from DNA modified chemically with N-acetoxy-ADCP and
      DNA adducts from the other compounds in their target organs. In the absence of a
      pattern of compound-related spots, we conclude that RF does not form DNA adducts
      having the potential to initiate neoplasia in these three tissues.

PMID- 11850975
TI  - Management of respiratory failure associated with acute exacerbation of COPD and
      the role of non-invasive ventilation (NIV).

PMID- 11850976
TI  - Role of Bi-pap in acute respiratory failure due to acute exacerbation of COPD.
AB  - OBJECTIVE: To assess the efficacy of Bi-level Positive Airway Pressure (Bi-pap),
      administered by nasal mask in patients with acute respiratory failure due to
      acute exacerbation of COPD. DESIGN: Prospective non-randomized study in a
      hospital setting. METHODS: Eighteen patients were recruited from those admitted
      in the Chest Unit of Jinnah Postgraduate Medical Centre, Karachi with acute
      exacerbation of COPD. Along with conventional treatment, Bi-pap was administered
      by a nasal mask. Arterial blood gas analysis, respiratory and heart rate and
      subjective sensation of dyspnoea, before and during Bi-pap application were
      monitored. RESULTS: The respiratory rate decreased from 33.2 +/- 5.3/min to 22.0
      +/- 3.5 (P < 0.001), heart rate also decreased from 113.2 +/- 7.6/min to 90.2 +/-
      11.9 (P < 0.001). A rise in pH was observed from 7.2 +/- 0.09 to 7.4 +/- 0.06 (P
      > 0.41 n.s.), PaCO2 decreased from 76.5 +/- 15.5 to 51.3 +/- 10.5 (P < 0.001).
      PaO2 also increased from 52.1 +/- 14.3 to 62.9 +/- 11.5 (P < 0.01). The mean
      hospital stay was shorter i.e., 10.6 +/- 5.6 days and the hospital mortality rate
      11.1%. Bi-pap administered by nasal mask was generally well tolerated with few
      minor complications. CONCLUSION: Bi-pap is particularly useful in patients
      presenting with acute respiratory failure due to acute exacerbation of COPD
      particularly in our setting where invasive ventilation is not easily available.

PMID- 11850977
TI  - Parental [correction of Perinatal] consanguinity: a risk factor for developmental
      delay in Pakistani children.
AB  - OBJECTIVE: To investigate the association of parental consanguinity and delayed
      development in terms of gross motor, fine motor, speech and social aspects in
      their children. METHODS: One hundred and seventy seven children (age 15 days--72
      months) were evaluated for their developmental status utilizing the Denver
      Developmental Screening Test (DDST). An unmatched case-control study design was
      used. Case group consisted of 94 children and control group 83 children. Odds
      ratios were calculated for parental consanguinity and delay in gross and fine
      motor, speech and social development in their children, for cases and controls,
      utilizing Binary Multiple Logistic Regression Analysis. Acquired delay was
      excluded through detailed birth history in both cases and control group
      respectively. RESULTS: Univariate analysis showed high significant Odds ratios
      for all areas of developmental delay (viz. gross and fine motor, speech and
      social development), between cases and controls (p < .001). At the multivariate
      analysis level however, our results showed no increased risk of parental
      consanguinity on delayed gross and fine motor, speech and social development in
      their children. CONCLUSION: Our results show no increased risk of parental
      consanguinity on delayed gross and fine motor, speech or social development (as
      measured by the DDST), in their children.

PMID- 11850978
TI  - Day care surgery at a university hospital--who is responsible after discharge.
AB  - OBJECTIVE: To computer the rate of morbidity and unplanned hospitalization
      amongst patients undergoing Day Care Surgery at this institute. METHODS:
      Retrospective study of all adult general surgical patients undergoing planned day
      care surgical procedures between November 1996 and December 1997. RESULTS: Six
      hundred and seventy four patients underwent ambulatory operations over one year.
      The morbidity rate was 6.2% and the rate of unplanned hospitalization was 13.6%.
      CONCLUSION: We conclude that timing of surgery and short duration operation on
      carefully selected patients is likely to reduce hospitalization. There is great
      scope of Day Care Surgery in developing countries and a major effort will be
      required to popularize it in Pakistan, which include development of
      infrastructure and patient education.

PMID- 11850979
TI  - Adrenocortical reserve in patients with active tuberculosis.
AB  - CONTEXT: In recent years several studies have documented decreased adrenal
      cortical reserve in patients with active tuberculosis. This reduced adrenal
      reserve could be an important factor in causing mortality and morbidity in these
      patients. OBJECTIVE: To study the adrenal cortical reserve and its relationship
      with disease duration and severity in patients with active tuberculosis. DESIGN
      SETTING AND PARTICIPANTS: Forty patients with confirmed active tuberculosis (28
      pulmonary and 12 extra-pulmonary) without clinical evidence of Addison's disease
      and 10 healthy, age and sex-matched subjects (controls) participated in this
      study. The study was conducted at Sher-i-Kashmir Institute of Medical Sciences,
      Srinagar, Kashmir. INTERVENTIONS: Adrenocorticotropic hormone stimulation test
      performed in both groups. MAIN OUTCOME MEASURES: Basal serum cortisol level and
      parameters of stimulated cortisol response (maximum increase of cortisol over
      basal, peak rise of cortisol and area under response curve). RESULTS: The mean
      basal cortisol levels were comparable between the two groups (P = 0.792). The
      parameters of stimulated cortisol response including maximum increase of cortisol
      over basal, the peak rise of cortisol and area under response curves were
      significantly lower in patients as compared to healthy controls (P < 0.001, 0.002
      and 0.049 respectively). However, these parameters were comparable between
      patients with active pulmonary and extra-pulmonary tuberculosis. Overall 14 (35%)
      patients exhibited sub-optimal cortisol response (3 negligible and 11 inadequate)
      to ACTH stimulation. ACTH stimulation revealed significant cortisol rise in
      patients with active tuberculosis at 4 and 8 hours only, whereas in healthy
      controls, the cortisol rise was more prolonged and continued up to 24 hours. The
      adrenocortical reserve was inversely related to the radiological severity of
      pulmonary tuberculosis (r, -0.41) and chronicity of active tuberculosis (r, 
      0.59). CONCLUSION: Patients with active tuberculosis have decreased
      adrenocortical reserve. The adrenocortical reserve seems to be inversely related
      to the radiological severity of pulmonary tuberculosis and chronicity of active
      tuberculosis.

PMID- 11850980
TI  - Complications of in-dwelling venous access devices: a single institution
      experience.
AB  - OBJECTIVE: To determine the complications of venous access devices (VADs) in
      cancer patients. SETTING: Retrospective study in a tertiary referral center with
      specialist hematology and oncology services. SUBJECTS: First one hundred
      consecutive patients who were implanted a VAD. All patients had an underlying
      cancer and the devices were inserted by the same surgeon. The duration of use of
      VADs and causes of their premature removal were noted. RESULTS: One hundred VADs
      (55 port-a-caths and 45 Hickman's lines) were inserted in a total of 89 patients
      over a 7.5 year period. Majority of patients had acute myeloid leukemia (22)
      gastrointestinal malignancies (20) breast cancer (19) and genito-urinary cancers
      (15). The mean duration of use was 110 days; 157 days for the port-a-cath and 53
      days for the Hickman's line. Nineteen devices (10 port-a-caths and 9 Hickman's
      lines) had to be removed prematurely. Two Hickman's lines got removed
      accidentally. The causes of premature removal included device failure (9), exist
      site infection (4), luminal infection (3) and tunnel infection (3). CONCLUSION:
      The mean duration of use and the complication rates are comparable with studies
      reported in the literature.

PMID- 11850981
TI  - Urbanisation and health related knowledge and attitudes of South Asian children.
AB  - OBJECTIVE: To study the differences in health related knowledge and attitudes of
      less and more urbanised 10-12 year old South Asian school children. METHOD: A
      total of 589 Asian children living in UK and in Pakistan were studied. Three
      groups of children were recruited from Punjab, Pakistan: rural (RrP, n = 100),
      middle income urban (MUP, n = 148) and high income urban (HUP, n = 159) and they
      were assigned urbanization rank (UR) 1, 2 and 3. Another two groups of children
      were recruited from Slough, UK: British Pakistani (BrP, n = 110) and British
      Indian (Brl, n = 71) and they were assigned urbanization rank 4 and 5
      respectively. Information about Cardiovascular Health (CVH) related knowledge,
      Health Locus of Control (HLC), smoking behaviour, self-perception of bodyweight
      and self-perception of activity level was collected through questionnaire. Actual
      weight status was judged by measuring body height and weight. Actual Physical
      Activity Level (PAL) was calculated from three day activity records kept by
      children. RESULTS: In general health related knowledge improved with urbanisation
      status. In all groups girls scored better on knowledge test than boys from the
      same group. HLC scores increased (indicate higher level of internal locus of
      control) steadily with urbanisation from UR 1-3. In most groups girls had
      slightly lower HLC scores. Smoking intentions were not related to UR. Validity of
      perceptions slightly improved with urbanisation rank only for activity level.
      CONCLUSION: Due to lack of knowledge and belief in external health locus of
      control, behaviour modification is likely to harder in less urbanized Pakistani
      groups. For the prevention of disease, efforts are required not only to increase
      the children's knowledge about health but also to increase awareness and
      understanding of healthy body weight, physical activity, hazards of smoking and
      to inculate belief in internal control over own health.

PMID- 11850982
TI  - Epidemiological features of aplastic anaemia in Pakistan.
AB  - OBJECTIVE: To complete the data on the demographic features of patients diagnosed
      to have aplastic anemia at a single institution over a 7.5 years period. METHODS:
      Demographic information was retrieved from the patients medical records
      retrospectively as well as prospectively of those patients who presented with
      features of aplastic anaemia. Their diagnosis was confirmed by performing a
      complete blood count and bone marrow trephine. RESULTS: One hundred and forty
      four patients were diagnosed to have aplastic anemia; there were 106 males and 38
      females. Their ages ranged from 2 to 75 years, with a median of 17 years, 112
      (77.7%) patients were below the age of 30 years. Severe aplastic anemia (SAA) was
      seen in 74 (51.4%), very severe (VSAA) in 24 (16.7%) and non-severe aplastic
      anemia (NSAA) in 46 (31.9%) patients. No obvious cause could be established for
      74.3%. Thirteen patients admitted using drugs known to cause AA and one was a
      radiographer (9%). Out of 44 patients tested, 7 (15.9%) were found to have either
      hepatitis B virus markers or antibody to hepatitis C at the time of diagnosis of
      AA. However it was difficult to establish a cause and effect relationship with
      either drugs or viruses. CONCLUSION: Aplastic anaemia is found to occur mostly in
      young males. The most common type was idiopathic severe aplastic anaemia.

PMID- 11850983
TI  - Mortality statistics in South Karachi.
AB  - OBJECTIVE: To create an awareness amongst the medical profession in Pakistan
      about the importance of mortality statistics in epidemiological research and its
      correlation with the cause of death statement. METHODS: The original death
      registration forms and the statistical information, compiled into a database by
      the District Municipal Corporation, South Karachi, for the years 1995 to 1998
      were evaluated. RESULTS: The total number of deaths reported from the District
      Municipal Corporation, South Karachi, for the years 1995 to 1998 were 7480. Of
      these 28% were females and 72% were males. The adult deaths were 99% whereas
      childhood deaths were 1%. The leading cause of death was cardiovascular disease
      (33%). However 49% of the deaths were classified as caused by non-specific or ill
      defined conditions. CONCLUSION: The maintenance of records and compilation of
      death registry data by the District Municipal Corporation, South Karachi is
      satisfactory. The coverage of deaths in the years 1995 to 1998 was reasonable.
      The degree of precision of the age statement was moderately good as the 'National
      Identity Card' copy accompanied each adult death notification. As the cause of
      death statement was non-specific in 49% of the deaths, this data will have
      limited use in research or health planning. It is therefore essential to
      emphasize the importance of the death certification process to the medical
      profession.

PMID- 11850984
TI  - Hormone replacement therapy menopause with a better future--a survey of views on
      hormone replacement therapy (HRT).
AB  - OBJECTIVE: To assess the views and prescribing practices of doctors regarding
      hormone replacement therapy (HRT). METHODS: In April 1999, 103 doctors from a
      teaching hospital participated in a survey. Using a self-administered
      questionnaire, subjects were contacted at the departments of Internal Medicine,
      Family Medicine, Obstetrics and Gynaecology, and Orthopaedics. RESULTS: Seventy
      two percent were below 40 years of age and 67% of the respondents were male. Most
      doctors believed that HRT decreases the risk of subsequent osteoporosis (97%),
      ischaemic heart disease (77%) and depression associated with menopause (64%).
      Doctors generally considered menopausal symptoms (90%), premature menopause
      (87%), surgical menopause (85%) and osteoporotic fracture (77%) as clear
      indications for hormone replacement therapy. Absolute contraindications to the
      therapy were stated as recent breast cancer (82%) and recent endometrial cancer
      (84%). Among the specialities covered, there were differing views on proposed
      duration of HRT. It was generally believed that a pelvic examination, cervical
      smear and mammography were pre-requisites when initiating and monitoring HRT.
      Majority (69%) felt that HRT should be offered to all menopausal women, assuming
      no contraindications and most (73%) did discuss HRT with their patients. However,
      less than 10% of the menopausal patients under their care were using HRT. Those
      doctors not in favor of universal offering of HRT (31%) considered unreliable
      patient follow up to be the main reason. Females were two times more likely to
      discuss HRT with their patients (p = .08). Doctors who discussed HRT with their
      patients were four times more likely to consider HRT for themselves or their
      spouses (p = .13). Gynecologists were eight times more likely to prescribe HRT
      than non-gynecologists (p = .001). CONCLUSION: Doctors are positively disposed to
      the universal offering, and use of HRT. Further studies are needed to understand
      a possible gap between perceived and actual prescribing practice.

PMID- 11850985
TI  - [The Hippocratic Oath: source of medical ethics].
AB  - The Hippocratic Oath is twenty-five centuries old. Probably drawn-up by
      Hippocrates himself, it intervenes in a particular cultural, political and
      religious context: that of Greece at the time of Pericles. It guaranteed the
      Asclepiad doctors of the continuity of their knowledge within their community.
      Medicine was highly esteemed because of it. The Oath, more than any other work of
      the Hippocratic collection, has outlived the centuries. It still remains one of
      the symbols of the medical profession. Despite its age, it provides insight into
      some of the questions of medical ethics even today. Its topicality is, without
      doubt, due to the transcendent nature of the values it proclaimed.

PMID- 11850986
TI  - [Motives for the prescription of antibiotics in the emergency department of the
      University Hospital Center in Nice. A prospective study].
AB  - OBJECTIVES: Since April 1999, we have set-up an infectious disease consultation
      in the emergency unit of the University Hospital in Nice. Unjustified
      antiobiotherapy is often initiated. We therefore conducted a survey to study the
      motives and validity of antibiotic prescriptions. METHOD: This prospective study
      was conducted in two phases. The first consisted in asking the emergency
      physicians prescribing antibiotics to fill-in a questionnaire giving information
      on the diagnosis established and the antiobiotherapy proposed. In the second
      phase, the diagnoses and corresponding treatments were submitted to 4 experts who
      assessed the acceptability of the diagnoses and the antibiotics prescribed. The
      experts only had access to the clinical and para-clinical data available.
      Moreover, their therapeutic judgement was based on previously published
      consensuses. RESULTS: The 6-month survey collected 117 questionnaires that could
      be analysed. The rate of error in diagnosis was of 33% (39/117). Thoracic x-rays
      could not be interpreted in 11% of cases. In single variant analysis, factors of
      erroneous diagnosis were due to its interpretation by an internist, the
      diagnostic category of "broncho-pulmonary infections" and the lack of
      documentation. In multi variant analysis, only the lack of documentation was
      related to erroneous diagnosis (OR = 5.5; IC 95% (2.03; 15.30), p < 0.0002). The
      rate of antibiotherapy not adapted to the diagnosis made by the physician was of
      32% (37/117). In 24 cases the modalities of the prescription were incorrect and
      in 13 cases the prescription was unjustified. Only the status of the prescriber
      (internist) was statistically associated with an antibiotherapy not adapted to
      the diagnosis (OR = 2.2; IC 95% (0.93; 5.26), p < 0.05). CONCLUSION: Unjustified
      antibiotherapy in an emergency unit is generally due to erroneous diagnosis of
      infection. The lack of documentation and inexperience of the prescribers appear
      to be the two elements contributing to unjustified antibiotherapy.

PMID- 11850987
TI  - [Thyroid orbital pathologies in ophthalmological settings].
AB  - OBJECTIVE: To illustrate the originality and diversity of an ophthalmologic
      pathology associated with a thyroid disease (OATD), we report 42 cases of
      patients hospitalised or having consulted an ophthalmologic department for this
      disease over a period of 4 years. METHOD: Each patient was assessed by an
      endocrinologist and an ophthalmologist. Data included the OATD severity score,
      date of occurrence compared with the thyroid disease and determination of thyroid
      function and immune abnormalities. RESULTS: Patients were aged a mean of 48.9 +
      15.3 years; 65% were women and 39% smokers. OATD preceded the thyroid disease in
      38% of cases, was concomitant in 40% and successive in 21%. Thirty-six percent of
      cases were mild, 45% moderate and 19% were severe. One patient out of 5 had
      exhibited a period of iatrogenic hypothyroidia. The majority (81%) presented with
      Basedow's disease; 14% Hashimoto's disease; 73% anti-TSH receptor antibodies and
      56% anti-thyroperoxidase antibodies. Two profiles of patients with OAMT were
      identified. A first group with severe OATD: Basedow's disease, presence of anti
      TSH receptor antibodies and a period of iatrogenic hypothyroidia in half of the
      cases. A second group in which the occurrence of OATD preceded diagnosis of a
      thyroid disease: generally non-severe forms with varying thyroid status, strongly
      related to the moment at which the patient consulted, compared with the
      progression of the ophthalmologic and thyroid affections. CONCLUSION: When faced
      with signs evoking OATD, these data emphasize the need for an evaluation of
      thyroid status and determination of the antibodies implied in Basedow and
      Hashimoto's disease. After initiation of synthetic anti-thyroid or radioactive
      iodine therapy, the evolution of the thyroid and ophthalmologic status of
      hyperthyroid patients must be carefully monitored.

PMID- 11850989
TI  - [Respiratory distress and bronchiolitis due to respiratory syncytial virus in an
      immunocompetent adult].

PMID- 11850988
TI  - [Self-poisoning with Datura stramonium. 3 case reports].
AB  - BACKGROUND: Datura stramonium is a hallucinogenic plant that causes serious
      poisoning. Due to its easy availability and strong anticholinergic properties,
      substance users and teens may use Datura stramonium as a drug. Consumption of any
      part of the plant can result in severe toxicity. CASE REPORTS: 3 cases of acute
      self-poisoning by ingestion of Datura stramonium are reported. The patients
      presented with a typical anticholinergic syndrome: agitation, confusion,
      hallucinations and combative behaviour; all of them had mydriasis, but dry mouth
      and tachycardia were less common. All these 3 subjects had a good prognosis but
      have required hospitalisation because of severe psychiatric derangement with
      agitated behaviour. The patients were favourably managed with only symptomatic
      treatment. DISCUSSION: This article reviews the clinical syndrome associated with
      the toxicity. The severity of hallucinations and confusion, associated with
      pupillary dilation, flushing, dry mouth, and tachycardia, are related with Datura
      intoxication. Symptomatic treatment is efficient. CONCLUSION: Primary care
      physicians might be informed about the abuse of Datura stramonium, often
      associated with substance misuse, and the need to educate risk-patients.

PMID- 11850990
TI  - [Current clinical aspects of HIV/AIDS].
AB  - OF NEW CLINICAL DEMONSTRATIONS: Since the use of HAART, morbidity and mortality
      in HIV-infected patients have decreased dramatically. But increased survival in
      these patients is associated with other diseases (malignant diseases,
      inflammatory reactions after initiation of HAART) and with drug toxicity
      (lipodystrophy, mitochondrial toxicity). TRANSMISSION AND REVELATION: Despite
      widespread information on HIV, new HIV-infected patients with an AIDS-defining
      illness are still detected. At present, heterosexuality is the most frequent risk
      factor for HIV-infection (51%). Pneumocystis pneumonia remains the most common
      opportunistic illness in HIV-infected patients (28%).

PMID- 11850992
TI  - [Advances in the domain of HIV].

PMID- 11850991
TI  - [Stress urinary incontinence in women. Physiopathology and surgical treatment
      using Burch's technique and TVT].
AB  - FROM PHYSIOPATHOLOGY TO TREATMENT: Urinary incontinence on effort in women is due
      to a default in sub-urethral anatomical structure, which leads to incontinence on
      effort (coughing, laughing, carrying heavy weights, physical activity). When re
      education fails, surgical treatment using Burch's technique or the placing of sub
      urethral TVT (Tension free Vaginal Tape) is generally proposed. BURCH'S
      TECHNIQUE: Burch's technique consists in an upper tract colposuspension via
      coelioscopy or laparotomy, under rachis or general anaesthesia. In the
      literature, the following rates of complete cure have been presented: 64 to 87%,
      75 to 95% and 63 to 89% respectively in the short, median and long term together
      with the cure of certain complications (vesicular instability, dysuria, secondary
      prolapse, infections). THE TVT TECHNIQUE: Developed in the early nineties, the
      placing of TVT is a mini-invasive technique requiring the use of polypropylene
      tape inserted vaginally under the urethra under rachis or local anaesthesia. It
      is associated with over 80% median term clinical efficacy and rare complications
      (vesicular perforation, arterial wounds, perineal haematoma, dysuria,
      infections).

PMID- 11850993
TI  - [The new frontiers of blood doping].
AB  - Blood oxygenation and peripheral perfusion are pivotal factors to optimize
      intensity and length of the muscular activity. Enhancement and optimization of
      oxygen delivery to peripheral tissues is associated with a substantial
      improvement of the athletic performances, especially in endurance sports.
      Remarkable progresses in medical research promoted the introduction and
      commercialization of novel methods and molecules for the therapy of severe
      systemic pathologies, characterized by detrimental peripheral oxygenation.
      Unfortunately, the evident benefits of some promising classes of molecules
      propitiated the gradual diffusion to some sport disciplines, in form of doping.
      Aim of this review is to give further insights into new techniques of blood
      doping, chiefly focusing on blood transfusion, oxygen-carrying blood substitutes,
      synthetic haemoglobin allosteric modulators and administration of substances
      promoting synthesis and maturation of erythrocytes.

PMID- 11850994
TI  - [Tumors of the testis: a paradigm of a curable neoplasm?].
AB  - Mortality from testicular cancer has been declining in the USA since the 1970's
      and in western Europe since the late 1970's, and the rates in the late 1990's
      were about 70% lower than in the 1970's. In Eastern Europe, however, some decline
      was observed only since the late 1980's and was substantially smaller (only
      approximately 20%). Consequently, a few hundred avoidable deaths from a curable
      neoplasm, mainly of young adults, are still registered in Eastern Europe. This
      underlines the urgency of implementation of available and effective therapeutic
      schemes for testicular cancer in Eastern Europe.

PMID- 11850995
TI  - [Infliximab in aggressive and refractory rheumatoid arthritis. A pilot study].
AB  - Rheumatoid arthritis is a chronic inflammatory disease with a progressive course,
      that frequently provokes permanent incapacity if not adequately treated.
      Rheumatoid arthritis may be not responsive to the common second line drugs. This
      study was aimed to treat 15 patients affected by severe refractory rheumatoid
      arthritis with infliximab. PATIENTS AND METHODS: Fifteen patients with refractory
      rheumatoid arthritis were treated with infliximab--monoclonal antibody direct to
      TNF alpha--in association with methotrexate or azathioprine. Infliximab was
      administered at the dosage of 3 mg/Kg at the weeks 0, 2 and 6 and then every 8
      weeks. RESULTS: About half patients ameliorated in agreement with both ACR 20
      criteria and DAS28 evaluation. The clinical improvement was accompanied by a
      reduction of the steroid daily dosage. No relevant side effects were observed.
      CONCLUSION: Infliximab is effective in a significant number of patients with
      severe rheumatoid arthritis, with a good tolerability.

PMID- 11850996
TI  - [Association between hepatocellular carcinoma and polycythemia vera].
AB  - The association of hepatocellular carcinoma (HCC) and polycythemia vera in a
      middle-aged caucasian man is described for the first time in this case report.
      The report underlines the necessity and the importance of a full, evidence-based
      investigation of the nature of polyglobuly in the course of HCC, a condition
      known to be associated to erythrocytosis, so far usually considered secondary to
      HCC, and not primary.

PMID- 11850997
TI  - [Systemic lupus erythematosus and HIV infection. A case report and review of the
      literature].
AB  - Although HIV infection is often associated with several rheumatic diseases, the
      coexistence of this retroviral infection and systemic lupus erythematous is
      extremely uncommon. Etiopathogenetic relationship between these disorders is very
      complex and still problematic, so that diagnostic workout, because of their
      extensive clinical and serological overlap. Generally, HIV-related
      immunosuppression improves lupus-associated symptoms, and antiretroviral therapy
      may lead to an autoimmune disease flare, subsequent to the increase of
      circulating CD4+ cell number. A HIV-infected female patient with systemic lupus
      erythematosus, occurred few months after the highly active anti-retroviral
      therapy initiation, is described.

PMID- 11850998
TI  - [Controversies on the efficacy of noninvasive ventilation in chronic obstructive
      pulmonary disease (COPD)].
AB  - Clinical studies have shown that noninvasive positive pressure ventilation (NPPV)
      have significant advantages in the treatment of respiratory failure due to COPD.
      Reduced intubation need, decreased complications and mortality and less
      hospitalization in intensive care unit are recognized benefits of NPPV. A general
      consensus has been reached that NPPV application in acute respiratory failure can
      decrease respiratory muscles effort and improve gas exchange, when performed in
      selected patients by an expert team. Application of long term NPPV in patients
      with advanced stable COPD and chronic CO2 retention is still controversial. The
      contrasting results were obtained from studies with small patients number, short
      time observation and different patient's selection. Therefore randomized and
      controlled studies with a great number of patients are essential to evaluate the
      effects of NPPV in stable COPD patients with chronic retention of CO2, not only
      in survival but also in quality of life.

PMID- 11851000
TI  - [Physiopathology of the enteric nervous system: recent advances and clinical
      implications].
AB  - Enteric neuropathies may significantly affect the patient's quality of life,
      although they have a fatal outcome only in a minority of cases. Motor derangement
      (often, hypomotility) is a typical feature of primary and secondary neuropathies
      affecting the myenteric plexus. This review addresses some pathophysiological
      aspects of enteric neuropathies and tries to outline the limitations of the
      experimental evidence obtained so far as well as some questions that can possibly
      receive an answer by applying new concepts and new techniques. In particular, the
      concept of neuronal plasticity, originally developed by investigators studying
      the central nervous system, is discussed and applied to the enteric
      microenvironment, with specific reference to adaptive phenomena occurring during
      intestinal inflammation. The role of neurotrophins and the potential therapeutic
      applications are also briefly discussed.

PMID- 11850999
TI  - [The discharge from hospital record of the patient with rheumatoid arthritis].
AB  - Rheumatoid arthritis is a chronic inflammatory disease characterised by
      diarthrodial joint involvement, where bone erosions are the first signs. Early
      diagnosis, polyarticular exacerbation, treatment unefficacy, concomitant disease
      or intollerance to therapy represent the reasons that often require hospital
      admission. The discharges's report is divided into sections. The reason of
      admission, clinical and laboratory findings, result of aimed tests performed, the
      treatment administrated, the conclusions in diagnosis favour and the suggested
      therapy are precised. The discharge's report represents an health iter
      conclusion, in which the medical services and certificative functions of
      charitable institutions are combined.

PMID- 11851001
TI  - [Vector-borne diseases. Recent advances in the diagnosis, treatment and
      prevention].
AB  - Vector borne diseases are infections transmitted by arthropods. The vector can
      mechanically spread the infectious disease or give hospitality to microrganisms
      for their biological cycle. The etiologic agents of these infections are viruses
      as yellow fever and Dengue, protozoans as plasmodium of malaria, Leishmania spp.,
      bacteria as Borrelia burgdorferi, Rickettsia spp. or worms as lymphatic
      filariasis. They are emerging infectious diseases for the epidemiological changes
      of our national territory (ex. Lyme disease) but especially for the significant
      increase of the imported forms. Malaria is the more important infection for its
      clinical management but also for its remote possibility of a further transmission
      in Italy. In this review are illustrated the recent progresses in the diagnosis,
      treatment and prevention of the main vector borne infections that the clinical
      physicians may frequently observe. It is very important to know these diseases
      because an adequate preparation and continuous updating are necessarily required.

PMID- 11851002
TI  - [Echocardiographic evaluation of ventricular hypertrophy].
AB  - Quantitative echocardiography is the gold standard for the evaluation of
      abnormalities in left ventricular (LV) geometry and systolic function,
      information very important for risk stratification, and also applicable in
      clinical practice when some conditions are met. Few primary measures (LV
      diameter, septal and posterior wall thickness) provide a valuable information
      which fully represents the type and degree of hemodynamic alteration. These
      measures should be collected ideally by M-mode tracings, but often M-mode
      examination cannot be performed. When M-mode is suboptimal, LV mass can be
      computed using two-dimensional imaging and the formulas used for M-mode. LV mass
      is expressed as an index normalized for some measure of body size. Normalization
      for height in meters to the power 2.7 can identify a higher proportion of
      individuals at high cardiovascular risk and provides a greater attributable risk
      than other methods of indexation. When LV hypertrophy develops to provide
      sufficient strength to compensate for hemodynamic overload, the increase in LV
      mass is not clearly associated with increased cardiovascular risk. In contrast,
      individuals with LV mass inappropriately high as compared to the value sufficient
      to compensate for hemodynamic load at a given body size present with a phenotype
      characterized by high cardiovascular risk, even in the absence of arterial
      hypertension.

PMID- 11851003
TI  - [Thiazolidinediones and PPARgamma system in repair of liver damage].
AB  - PPAR-gamma belongs to the nuclear hormone receptor superfamily and its ligands
      include antidiabetic drugs of the thiazolidindione class, and endogenous
      molecules, including eicosanoids and fatty acids. PPAR-gamma is involved in the
      pathophysiology of obesity and type II diabetes. More recently, accumulating
      evidence suggests its role in atherosclerosis, inflammation and cancer. Recent
      data obtained in cellular models of liver fibrosis indicate that PPAR-gamma
      activation results in the inhibition of the processes leading to the development
      of liver fibrosis. These studies identify potential novel therapeutic strategies
      for the treatment of liver fibrosis.

PMID- 11851004
TI  - EMG activity of the orbicularis oculi muscle in normal and in individuals
      indicated to receive eye prosthesis, before and after its placement.
AB  - To analyze comparatively through electromyography (EMG) the orbicularis oculi
      muscle from normal patients and those indicated to receive eye prosthesis
      (treated patients), it was studied 24 male patients with a mean age of 32.5 years
      old, who were divided into 2 groups as follows: 12 individuals with absence of
      the left eyeball and indicated to receive prosthesis (treated); 12 normal
      individuals (control). The work was performed in 4 different clinical conditions:
      initial resting; normal opening and closure of the eyelids; forced opening and
      closure of the eyelids and final resting, before and after placement of eye
      prosthesis. The exams were made using an Electromyograph K6-I Light Channel and
      Surface Electrodes. By the results obtained under the work conditions, we can
      conclude that: the use of eye prosthesis did not interfere in the clinical
      conditions of opening and closure of the eyelid; the loss of the eyeball
      increases the EMG activity of the orbicularis oculi muscle; the use of eye
      prosthesis for a period of 7 days, was not enough to diminish the muscular
      activity, even its perfect adaptation been evidenced clinically.

PMID- 11851006
TI  - Diabetic polyneuropathy. Axonal or demyelinating?
AB  - Diabetic polyneuropathy is the most common subgroup of diabetic neuropathy, but
      its nature is controversial as it might be demyelinating and/or axonal. We have
      tried to determine whether diabetic polyneuropathy is electrophysiologically
      axonal, demyelinating, or both. We have studied the sural and peroneal nerves and
      the electromyographies of leg muscles in 50 healthy subjects (average age 67.2
      years, range 45 to 84 years), in 50 diabetic patients (average age 66.34 years,
      range 44 to 82 years) showing no symptoms and/or signs of polyneuropathy (DP1),
      and in 50 diabetic patients (average age 67.10 years, range 49 to 87 years)
      showing symptoms and/or signs of polyneuropathy (DP2). The amplitude (AMP) of
      sural and peroneal nerves in healthy and DP1 subjects was similar. Conduction
      velocity (CV) of sural and peroneal nerves was slower in DP1 subjects than in
      healthy subjects. DP2 subjects showed AMP and CV values significantly lower than
      those in DP1 subjects, and signs of acute and chronic denervation/reinervation
      were found in the leg muscles. We believe that this result indicates that
      diabetic patients have two types of polyneuropathies: a demyelinating disease
      that could appear in diabetic patients with and without symptoms of
      polyneuropathy, and an axonal loss that is responsible for most of the symptoms.

PMID- 11851007
TI  - Electromyographic validation of the trapezius and serratus anterior muscles in
      frontal-lateral cross, dumbbells exercises.
AB  - Based on the lack of electromyographic researches on sport and programmes of
      physical conditioning, we can say that it is necessary to reexamine some
      exercises routinely used in the programmes of physical conditioning. Thus, the
      trapezius and serratus anterior muscles were studied electromyographically so
      that we could evaluate the validity in some ways of execution of the frontal
      lateral cross, dumbbells exercises for the development of these muscles. We
      analyzed 24 male volunteers, 18 to 25 years old, using a 2-channel TECA TE 4
      electromyograph and Hewlett Packard surface electrodes. For the execution of the
      exercise it was used a supine bench, a straight board and two bars of 40 cm made
      of light wood. The results showed that TS acted preferentially in standing
      modality and in the inclined supine modality, however with activity levels that
      do not justify its inclusion in physical fitness programmes.

PMID- 11851005
TI  - Nerve refractory period in early polyneuropathies.
AB  - The refractory period of the sural nerve was evaluated in 115 patients with
      suspected polyneuropathy of various origin. They were asymptomatics or with
      minor, mainly sensitive, disturbances. In all the conventional neurophysiologic
      examination (motor and sensory velocities, distal latencies and F-waves of the
      peroneal, ulnar and sural nerves) was normal. The absolute refractory period
      (ARP) was defined as the shortest interstimulus interval at which a response to
      the second stimulus could be recorded. The relative refractory period (RRP) was
      defined as the interstimulus interval at which the responses to the first and to
      the second stimulus have equal latencies. The ARP was prolonged in 13 patients
      and the RRP in 28. In all, the refractory period was prolonged in 38 patients
      (33%). In any but three patients the ARP and the RRP were prolonged together.
      Thus the refractory period is more sensitive than the conventional
      neurophysiological examination in detecting early neuropathy. Moreover the ARP
      was modified in 2/9 patients with Steinert's myotonic dystrophy without clinical
      or electrophysiological signs of peripheral neuropathy.

PMID- 11851008
TI  - SPECT changes and their correlation with EEG changes in tuberculous meningitis.
AB  - OBJECTIVE: In tuberculous meningitis (TBM) blood flow may be altered due to
      associated vasculitis, hydrocephalus and raised intracranial pressure.
      Electroencephalography (EEG) and single photon emission computed tomography
      (SPECT) provide information about electrical activity and regional cerebral blood
      flow respectively. This study aims at the correlation of EEG and SPECT changes in
      patients with TBM. METHOD: Sixteen patients with TBM whose age ranged between 5
      and 62 years and 3 of whom were females were subjected to clinical, radiological
      (CT and/or MRI), EEG and SPECT studies using 99mTc ethylene cystine dimer (ECD).
      Ten patients were in stage III and 3 each in stage II and stage I meningitis.
      Cranial CT scan was carried out in 15 and MRI in 4 patients. Hydrocephalus was
      present in 9, infarction in 7 and tuberculoma in 5 patients. RESULTS: SPECT
      studies were abnormal in all except 2 patients revealing basal ganglionic
      hypoperfusion in 14 and focal cortical hypoperfusion in 9 patients. The EEG was
      abnormal in 11 patients which included delta slowing in 5, theta slowing in 6,
      frontal intermittent rhythmic delta activity (FIRDA) in 3 and epileptiform
      discharges in 2 patients. All the patients with abnormal EEG had abnormal SPECT
      study except 1. In 4 patients, EEG was normal although there was subcortical
      hypoperfusion on SPECT. In spite of high frequency of focal cortical
      hypoperfusion (9 patients), EEG revealed focal abnormality in 3 patients only.
      CONCLUSION: It can be concluded that the SPECT reveals more frequent
      abnormalities compared to EEG and CT scan. Cortical hypoperfusion with or without
      basal ganglia hypoperfusion is associated with FIRDA and diffuse delta slowing on
      EEG.

PMID- 11851009
TI  - Electromyographic analysis of the extending muscles of the knee during functional
      activities.
AB  - The purpose of this study is to analyze the behavior of electrical activity of
      the muscles vastus medialis oblique (VMO), vastus medialis long (VML), and,
      rectus femoris (RF) during functional activities. The electromyography of the
      VMO, VML and RF muscles were analyzed in ten healthy volunteers. Signs were
      collected through superficial electrodes and a electrogoniometer, connected to a
      signal condition module. The analysis of the results after treating the signals
      shows us that there is a similar electromyographical behavior in the three
      studied muscles. Therefore, these discoveries suggest a common electrical
      behavior pattern especially between VMO and VL muscles in healthy volunteers.

PMID- 11851010
TI  - Effects of elbow flexion on radial nerve motor conduction velocity.
AB  - The position of the elbow while conducting motor studies of the radial nerve is
      generally extended (15) or slightly flexed (10), but little is known about the
      effects of elbow flexion on the radial motor conduction velocity. We attempted to
      measure the effects of the elbow position on the radial motor conduction
      velocity, as well as directly measure the change in the length of the nerve at
      different elbow positions in the cadaver. In addition, we established normal
      values for the radial F-wave with the recording electrode on the extensor indicis
      proprius muscle. Radial motor nerve conduction was studied in 25 normal subjects
      to evaluate the effect of 3 different elbow positions (0 degree, 45 degrees, and
      90 degrees) on motor conduction velocity (MCV) across the elbow. Direct (in situ)
      radial nerve measurements were performed on four cadaver specimens to compare
      changes in nerve length during elbow flexion. Normal values for radial F-wave
      latencies recording from the extensor indicis proprius muscle were also
      determined in 23 subjects. The radial MCV decreased significantly as the elbow
      flexed from 0 degree to 90 degrees. The normal range of values for radial motor
      nerve conduction at 0 degree of elbow flexion was 71.7 +/- 4.7 m/s, 68.9 +/- 4.9
      at 45 degrees of elbow flexion, and 62.0 +/- 6.4 m/s at 90 degrees elbow flexion.
      Actual (in situ) radial nerve measurements were also found to decrease in length
      as the elbow flexed. The minimal radial F-wave latency was 19.8 +/- 3.7
      milliseconds. For routine determination of motor nerve conduction velocity across
      the elbow, we recommend that the elbow be fully extended, as the distance
      measurement most accurately reflects the maximum anatomic length of the nerve. We
      also feel that the radial nerve F-wave latency is readily obtainable from the
      extensor indicis proprius muscle.

PMID- 11851011
TI  - Masked myoclonus in corticobasal degeneration: neurophysiological study of a
      case.
AB  - A single case study of a 58 year-old male with right asymmetric apraxia and
      akinetic-rigid syndrome is described. Brainimaging scans (MRI, SPECT) indicated
      asymmetric cortical atrophy compatible with the diagnosis of Corticobasal
      Degeneration. Reflex myoclonus was absent and myoclonic discharges only appeared
      in response to pharmacological treatment of limb dystonia and rigidity.
      Electromyographic evidence of jerky movements was recorded only in the affected
      right hand and forearm after muscle relaxation, and myoclonus was not preceded by
      an EEG paroxysm. The cortical components of the correspondent SEPs were not
      increased in amplitude while LLRs recordings showed a late response over the
      muscles of the affected side. Furthermore, the duration of post MEP silent period
      was bilaterally reduced. This single case study report points out that sometimes
      myoclonus in Corticobasal Degeneration can be masked by the presence of increased
      muscle tone.

PMID- 11851012
TI  - Influence of hyperbaric environment on physiological tremor.
AB  - The effect of pressured environment from 1 to 24 ATA (Atmosphere Absolute) on
      total power spectrum (TP) of physiological tremor, whose value was the sum of
      power spectra for frequency range in 0.5-50 Hz, was investigated. The main
      effects obtained were as follows. (1) In the case of 3 ATA, TP during the
      pressure holding period denoted a similar value as the value in 1 ATA. In the
      latter half of the period, the TP increased. When the pressured environment is 4
      ATA, in which the partial pressure of the nitrogen gas was 3.6 ATA, the TP
      decreased during the pressure holding period compared with the value in 1 ATA.
      Nitrogen narcosis was recognized at the partial pressure of 3.6 ATA, thus the
      effect denoted a decrease of TP. (2) In the cases of 16 and 19 ATA using heliox
      gas, during the pressure holding period, TP decreased compared with the value in
      1 ATA, but in the case of 24 ATA the value increased. The partial pressure of
      helium gas of 23.6 ATA indicated a high pressure nervous syndrome, therefore, the
      influence of high pressure on TP was recognized as one of the causes of the
      increase of TP. (3) The influence of inhibitors of the autonomic nervous system
      on TP during the pressure holding period of 3 ATA was recognized. After intake of
      the inhibitor for the parasympathetic nerve (atropine) during the pressure
      period, TP increased, while for the intake of the inhibitor for the sympathetic
      nerve (propanol), TP decreased.

PMID- 11851013
TI  - Growth behaviour of a spore forming probiotic strain in the gastrointestinal
      tract of broiler chicken and piglets.
AB  - The growth behaviour of the probiotic strain Bacillus cereus var. toyoi in the
      gastrointestinal tract of broiler chicken and suckling piglets was evaluated. The
      strain germinated rapidly in intestinal samples from both animal species. Less
      than 10% of spores were recovered from the chicken crop and piglet stomach,
      respectively. Lumen samples and mucosal tissues from the hind gut of piglets
      displayed increasing colonization of the probiotic strain throughout the trial
      period. After oral administration of vegetative cells to broiler chicken and
      weaned piglets, sporulation was detected in all intestinal samples. The
      distribution of spore CFU indicated repeated germination and sporulation during
      the intestinal passage in piglets. B. cereus var. toyoi was not able to colonize
      the intestinal tract of both animal species. However, the probiotic strain was
      detected in suckling piglets before uptake of B. cereus var. toyoi supplemented
      feed. It is concluded that B. cereus var. toyoi germinates rapidly in broiler
      chicken and piglets, which is a necessary prerequisite for its possible probiotic
      effects. Germination and in vivo sporulation of vegetative cells indicated that
      the probiotic strain was metabolically active in the intestine of both animal
      species.

PMID- 11851014
TI  - Studies on the mode of action of non-starch-polysaccharides (NSP)-degrading
      enzymes in vitro. 2. Communication: effects on nutrient release and hydration
      properties.
AB  - By use of an in vitro model, the effects of NSP-degrading enzymes on the cage
      effect and the hydration properties were demonstrated using wheat bran. The in
      vitro model simulates the conditions (pH, dry matter, temperature and transit
      time) in the fore sections of the porcine gastro-intestinal tract (GIT) by
      neglecting endogenous enzyme activities. Enzyme treatment caused a dose-dependent
      increase in wheat bran solubility and thus resulted in improved protein and
      mineral release from the insoluble NSP fraction. Up to 17% protein and 40% crude
      ash from the insoluble NSP-fraction were dissolved after enzyme treatment.
      Hydrating properties of wheat bran were strongly affected by enzyme treatment and
      particle size. Water-binding capacity (WBC) and water-holding capacity (WHC)
      decreased with increasing enzyme dosage in dependence on particle size. The
      studies confirmed the applicability of the tested in vitro model as a useful tool
      for preliminary tests to estimate the effects of NSP-degrading enzymes on
      nutrient release and changes in some physico-chemical properties.

PMID- 11851015
TI  - Effect of antibiotics, 2-bromoethanesulfonic acid and pyromellitic diimide on
      methanogenesis in rumen ciliate cultures in vitro.
AB  - The effects of penicillin G, streptomycin, chloramphenicol, 2-bromoethanesulfonic
      acid and pyromellitic diimide on total gas, methane, volatile fatty acid
      production and food degradability after 24 h of incubation in vitro were
      investigated in the cultures of two rumen ciliates. The inocula of both rumen
      ciliates Entodinium caudatum and Epidinium ecaudatum were used at a volume of 34
      ml into the 50 ml glass syringes together with the feed and compounds tested.
      Despite penicillin G--streptomycin treatment methane production in both cultures
      was significantly decreased by the inhibitors for Epidinium ecaudatum. Methane
      production of the bacterial fraction of both protozoan species was significantly
      lower than in the whole cultures. No epifluorescence of methanogens on (or in)
      the cells of Entodinium caudatum was observed in contrast to Epidinium with which
      strong epifluorescence of methanogens on the cell surface was detected.
      Microscopic observation could indicate that the methane production by Entodinium
      caudatum was probably caused by their intracellular methanogenic activity, while
      methane production by Epidinium ecaudatum could be related to both the
      methanogenic bacterial fraction from their external surface and probably also to
      intracellular activity. Decreased feed degradability and differences in the
      fermentation end products accompanied the inhibition of methanogenesis in both in
      vitro cultures. Entodinium caudatum appeared to be more sensitive than Epidinium
      ecaudatum to the compounds tested.

PMID- 11851016
TI  - Sugar beet mash silage as a component of a total-mixed-ration for dairy cows-
      effects on parameters of digestion and animal performance.
AB  - Sugar beet mash silage (BMS) was offered in amounts up to 35% of DM to dairy cows
      as a component of a total-mixed-ration (TMR). Barley and molasses in the control
      ration were replaced by BMS half in ration BMS 1/2 and in total in ration BMS 1/1
      on the basis of the calculated contents of net energy for lactation. Two trials
      were carried out. In trial I each ration was tested on parameters of rumen
      fermentation and digestibility of crude nutrients using 4 Holstein cows with
      rumen fistula. Chewing activity was tested on 2 Holstein cows for each ration.
      With the BMS rations the ruminal NH3 concentration was lower and the drop in pH
      was less than in the control ration. The pattern of volatile fatty acids in the
      rumen fluid from the BMS groups tended towards more propionic and butyric acid.
      The feeding of BMS showed no negative impact on chewing and rumination. Energy
      digestibility raised significantly from 59.8% in the control ration to 72.6% in
      the BMS 1/1 ration. In trial II the same rations were fed in a change-overdesign
      to a herd of 24 Holstein cows to test feed intake and animal performance. The
      results showed no significant effects of BMS rations on DM intake and milk
      production. The results of both trials indicate that even high amounts of cereals
      can be replaced by BMS without negative effects on rumen fermentation, milk yield
      and milk composition with slight drop in fat content. For a better handling of
      BMS, it is of advantage to include it in a TMR.

PMID- 11851017
TI  - The enhancement of the nutritive value of mango seed kernels for poultry by
      thermal treatment and radiation processing.
AB  - Raw seed kernels of local mango varieties (Magnifera indica L.) were analyzed for
      composition, levels of trypsin inhibitors, tannins, cyanogenetic glucosides, in
      vitro protein digestibility and apparent metabolizable energy (AMEN) as being
      effected by boiling, autoclaving as well as irradiation at 5, 10, 15, and 20 kGy.
      The air-dry mango seed kernels (MSK) contained CP 70 g kg-1, EE 128 g kg-1, and
      tannins 67 g kg-1. Compared with raw kernels the contents of trypsin inhibitory
      activity (30 TIU g-1) and cyanogenetic glucosides, measured as hydrocyanic acid
      (71 mg kg-1), were lowered by boiling, autoclaving and radiation treatments.
      Tannin content (67.2 g kg-1 in raw kernels) was decreased only by boiling or
      autoclaving, but irradiation did not introduce any effect. The low in vitro
      protein digestibility and AMEN values of raw MSK were enhanced by processing. The
      improvements were paralleled to reductions in trypsin inhibitory activity,
      cyanogenetic glucosides and tannin contents. Greater improvements were noticed
      with boiling and autoclaving than with irradiation alone. Autoclaving for 30 min
      plus irradiation treatment up to 20 kGy increased the in vitro protein
      digestibility and AMEN by 139% and 72%, respectively. These results indicate that
      tannins, trypsin inhibitors and cyanogenetic glucosides are responsible for the
      poor nutritive value of MSK. The effects of feeding 200 g kg-1 raw or processed
      MSK on the performance of broiler chicks were examined. The inclusion of raw
      kernel affected body weight gain and feed consumption, while weight gain of birds
      fed the autoclaved (30 min) plus irradiated (20 kGy) kernels was significantly
      more improved than by the other treatments. However, feed conversion ratio was
      not significantly different between groups fed the processed MSK. The results
      showed that the combination of autoclaving for 30 min plus irradiation up to 20
      kGy upgraded the nutritive value more than the other tested treatments and that
      this method is most effective in processing MSK to be used as animal feed.

PMID- 11851018
TI  - Effect of folic acid supplements on homocysteine concentration in plasma of
      gestating sows.
AB  - An experiment comprising 19 German Landrace sows was established to evaluate the
      effect of folic acid supplements (10 mg/kg concentrate) on homocysteine and folic
      acid concentration in plasma and serum, respectively, of highly pregnant sows as
      compared to an unsupplemented control (basal diet contained 0.62 mg folic acid/kg
      concentrate). Blood samples were taken between day 75 and 110 of gestation for
      homocysteine analysis and on day 100 of gestation for folic acid determination.
      Due to the folic acid supplements serum folic acid concentration increased
      significantly (104 nmol/l in controls and 140 nmol/l in supplemented sows). In
      contrast, homocysteine concentration in the plasma was not significantly
      influenced by folic acid supplements (16.6 mumol/l in controls and 15.2 mumol/l
      in supplemented sows). Further investigations seem to be necessary to clarify the
      physiology of homocysteine metabolism in swine.

PMID- 11851020
TI  - The effectiveness of an Escherichia coli phytase in improving phosphorus and
      calcium bioavailabilities in poultry and young pigs.
AB  - The effectiveness of an Escherichia coli phytase in comparison with a
      commercially available Aspergillus phytase in improving the bioavailability of
      phosphorus in broilers, layers and young pigs was studied in three separate
      experiments. Three basal diets, marginally deficient in dietary P mainly provided
      as phytate, were formulated. Both phytases were added to the diets at the rate of
      500 U/kg diet. The phytases significantly (P < or = 0.05) improved the
      availability of phytate P to broilers, layers and young pigs. Aspergillus and E.
      coli phytases enhanced the pre-caecal digestibility of P by 11 and 29% for
      broilers and 18 and 25% for layers, respectively. Total tract digestibility of P
      (P balance) was also enhanced but with smaller magnitude. In pigs, total tract
      digestibility of P was improved by 33 and 34% by Aspergillus and E. coli
      phytases, respectively. Under the conditions of this study, it was observed that
      E. coli consistently, though with small magnitude in layers and pigs, enhanced
      the availability of phytate P at the same range or slightly better than
      Aspergillus phytase. It was only in pigs that the availability of Ca was
      significantly (P < or = 0.05) improved by addition of both phytases. It can be
      concluded that E. coli phytase is highly effective in improving the
      bioavailability of phytate P to broilers, layers and young pigs. This seems to be
      based on the high proteolytic stability of the enzyme in the digestive tract, as
      shown recently.

PMID- 11851019
TI  - Effects of cell wall degrading enzymes on carbohydrate fractions and metabolites
      in stomach and ileum of pigs fed wheat bran based diets.
AB  - Pigs were fed diets containing 40% wheat bran incubated with a water: acetic acid
      mixture (control, C) and a cellulase (Cel-i) or xylanase (Xyl-i) preparation or
      with addition of the cellulase (Cel-a) or xylanase (Xyl-a) preparation
      immediately before feeding. Stomach and ileal samples were analysed for pH,
      osmolality, soluble saccharides, volatile fatty acids (VFA) and lactic acid.
      Incubation of wheat bran resulted in a small reduction of NDF and an increase in
      the amount of soluble starch, B-glucans and saccharides (glucose, xylose and
      arabinose), especially after incubation with the cellulase preparation. Two hours
      after feeding, significantly higher arabinose and xylose concentrations were
      present in the stomach for diets Cel-i, Cel-a and Xyl-i. In the ileum xylose and
      arabinose concentrations were higher 2 to 4 and 6 to 8 hours after feeding the
      enzyme-treated diets. In stomach and ileum there were no differences between the
      diets in pH, osmolality, VFA and lactic acid concentrations, but ileal VFA
      concentration from 4 h after feeding tended to be higher for diets Cel-i and Xyl
      i. It can be concluded that the amount of soluble saccharides in stomach and
      small intestine and the ileal VFA concentration may be increased by cell wall
      degrading enzyme preparations.

PMID- 11851021
TI  - Influences of wet feeding and supplementation with ascorbic acid on performance
      and carcass composition of broiler chicks exposed to a high ambient temperature.
AB  - In two experiments was investigated whether feeding with an air-dry feed mixed
      with different amounts of water and/or supplemental ascorbic acid affect
      performance and carcass compositions of broilers exposed to a high ambient
      temperature (35 to 37 degrees C for 8 h/d and thermoneutral for 16 h/d). In the
      first trial, 64 one-week-old male broiler chicks were fed ad libitum in four
      dietary treatment groups for a 6-week period. Experimental mash diets were
      prepared by mixing a maize-soybean based standard broiler starter or finisher
      with tap water in the ratios of 0.0:1.0, 0.5:1.0, 1.0:1.0 and 1.5:1.0 (water:air
      dry feed, w/w). More water in the diet increased BWG, DMI, abdominal fat and
      carcass weight, carcass CP, crude fat, but it deteriorated DM conversion
      efficiency. In the second experiment, 64 one-week-old male broiler chicks were
      given air-dry or wet (water:feed, 1.5:1) starter or finisher diets without or
      with ascorbic acid supplementation (0 and 250 mg/kg air-dry feed, resp.) ad
      libitum for a 6-week period. Ascorbic acid supplementation increased BWG, carcass
      weight and carcass CP significantly, while reducing carcass crude fat content.
      However, feeding broilers with a diet mixed with water in a ratio of 1.5:1.0
      increased BWG, DMI, carcass weight and carcass lipid markedly, but deteriorated
      DM conversion efficiency. There was also a significant interaction between
      ascorbic acid and wet feeding, whereby ascorbic acid supplementation induced a
      significant reduction in carcass lipid contents of broilers fed on air-dry diets
      but not on wet diets. It is concluded that wet feeding, especially an addition of
      150% water to produce a porridge like consistency, improved growth performance by
      increasing fat, ash and protein deposition in the body, while reducing DM
      conversion efficiency. It is also concluded that under heat stress supplemental
      ascorbic acid in air-dry diets stimulates broiler performance but not in wet
      diets.

PMID- 11851022
TI  - High versus low protein diets to mink--postprandial plasma urea and creatinine
      response, osmotic load and pattern of nitrogen and electrolyte excretion.
AB  - Nitrogen balance, pattern of excretion of nitrogenous end-products, endogenous
      urinary N excretion, postprandial plasma urea and creatinine, osmotic load,
      urinary electrolyte excretion and water intake/output relationships were studied
      in 12 adult female mink fed a high protein diet (HP; n = 6) providing about 155 g
      protein/kg or a low protein diet (LP; n = 6) providing about 95 g protein/kg. Two
      balance periods of each 3 d were used and diets were fed raw or cooked. After the
      last balance period followed a 48 h fasting period. Postprandial plasma urea and
      creatinine were studied for 48 h following a test meal given after an overnight
      fast. Osmotic load was determined based on collection of non-acidified urine
      carried out during 48 h. Level of protein supply did not affect N balance, being
      close to zero, whereas slightly negative balances were achieved for fasting
      animals. Protein supply was clearly reflected in excretion of urinary urea and
      allantoin but not in creatinine and uric acid. Endogenous urinary N excretion was
      estimated by a second order regression equation giving an intercept of 280
      mg/kg0.75. Post-prandial plasma urea concentrations were strongly influenced by
      protein supply, HP animals having substantially higher peaks than LP animals, but
      values returned to fasting values within 24 h after the test meal. Plasma
      creatinine followed a biphasic pattern with a peak about 2 h after feeding and a
      nadir approximately 6 h after feeding. Physical form of diet influenced
      postprandial urea, animals fed raw diets having a higher peak, but not
      creatinine. The HP diet provided almost the double osmotic load of the LP diet
      and a corresponding increase in urine volume. The resulting water balances were
      identical irrespective of diet, showing that water intake/output relationships
      are very accurately regulated.

PMID- 11851023
TI  - Effect of dietary medium chain triacylglycerols on plasma triacylglycerol levels
      in horses.
AB  - The hypothesis tested was that the feeding of medium chain triacylglycerols (MCT)
      to horses would raise the level of plasma triacylglycerols by increasing the
      availability of glucose as lipogenic substrate, implying that the MCT effect
      would be greater with glucose in the diet instead of cellulose. A Latin square
      experiment was carried out with 4 horses and 4 dietary treatments. The
      experimental periods lasted 21 d. Blood samples were taken 16 h after feeding.
      The diets consisted of hay and experimental concentrates, differing in fat source
      (MCT or soybean oil) and carbohydrate source (corn starch plus glucose or
      cellulose). The dietary variables, MCT or soybean oil, provided on average 27% of
      total dietary net energy, while glucose plus constarch or cellulose provided 33%.
      The feeding of MCT versus soybean oil raised the level of plasma triacylglycerols
      significantly from 196.7 +/- 30.2 to 427.3 +/- 85.7 mmol/l and that of VLDL
      cholesterol from 0.028 +/- 0.01 to 0.069 +/- 0.01 mmol/ml. As based on analysis
      of variance, for the four experimental diets there was no significant effect of
      carbohydrate source and no fat-carbohydrate interaction. Thus, the hypothesis was
      rejected. When the diets contained soybean oil, cellulose versus starch plus
      glucose produced significantly greater increase plasma triacylglycerols. This
      carbohydrate effect was not seen when horses were fed the MCT diets. The
      experimental concentrates did not differently influence the concentrations of
      plasma glucose, total serum cholesterol, phospholipids, insulin, free fatty acids
      and the activity of post-heparin lipoprotein lipase. We suggest that the MCT
      induced increase in plasma triacylglycerols is related to an increase in hepatic
      VLDL secretion, with the extra substrate for increased synthesis of
      triacylglycerols being the acetyl-CoA derived from the hepatic oxidation of
      medium chain fatty acids.

PMID- 11851025
TI  - Effect of potassium diformate in combination with different amounts and sources
      of excessive dietary copper on production performance in weaning piglets.
AB  - Three studies with each 96 weaning piglets were conducted to evaluate the
      combinatory effect of potassium diformate and high dietary doses of Cu on
      production performance. In Exp. 1, increasing dietary Cu (25, 75, 125, 175 ppm
      Cu) were tested at either no or 1.8% potassium diformate. In Exp. 2, rising
      dietary levels of potassium diformate (0%, 0.6%, 1.2% and 1.8%) were tested at
      either 25 or 175 ppm Cu. In Exp. 3, a basal dietary Cu content of 15 ppm was
      compared with dietary Cu levels of 95 or 175 ppm, each of them added as either Cu
      sulphate or Cu amino acid chelate or Cu formate. Rising dietary additions of
      potassium diformate and Cu improved weight gain, feed intake and feed conversion
      rate of piglets. The combination of potassium diformate and Cu failed to act
      additively at highest dose levels of the two supplements. Cu sulphate was
      efficient as growth stimulating additive in all 3 experiments, Cu formate failed
      to stimulate production performance. Cu chelate tended to depress production
      performance and to increase blood plasma Cu compared to equivalent amounts of Cu
      from Cu sulphate.

PMID- 11851024
TI  - Further survey of the occurrence of Fusarium toxins in wheat grown in southwest
      Germany.
AB  - A total of 53, 54, 57, 52 and 60 wheat samples for feed use were collected
      randomly after the 1989, 1990, 1991, 1992 and 1993 crops, respectively, from
      farms in an area of southwest Germany. Deoxynivalenol (DON), 3- and 15
      acetyldeoxynivalenol (3-, 15-ADON), nivalenol (NIV), HT-2 toxin (HT-2), T-2 toxin
      (T-2), diacetoxyscirpenol (DAS), and fusarenon-X (FUS-X) were determined by gas
      chromatography, combined with mass selective detection (GC-MS), zearalenone
      (ZEA), alpha- and beta-zearalenol (alpha-beta-ZOL) were determined by HPLC. DON
      was the major toxin, with incidences at 77 to 93% and mean contents at 167 to 735
      micrograms/kg. In contrast, incidences of ZEA, 3-ADON, NIV, HT-2, and T-2 were at
      13 to 37%, 10 to 44%, 15 to 67%, 0 to 11%, and 0 to 12%, respectively, with mean
      contents in positive samples between 2 and 73 micrograms/kg, except for 948
      micrograms/kg 3-ADON in samples from 1993. 15-ADON and FUS-X were assayed in
      samples from 1991, 1992 and 1993. 15-ADON was found in 0 to 11% of samples at
      mean levels < or = 17 mu/kg, DAS, alpha- and beta-ZOL, and FUS-X were not
      detected in any sample. Over the years, incidences and levels of toxins remained
      constant, decreased or increased, with most differences between years being
      slight and insignificant. The risk for livestock due to DON, HT-2 and ZEA was
      estimated based on maximum tolerated levels recommended for these toxins in some
      countries.

PMID- 11851026
TI  - Guidelines for brain radionuclide imaging. Perfusion single photon computed
      tomography (SPECT) using Tc-99m radiopharmaceuticals and brain metabolism
      positron emission tomography (PET) using F-18 fluorodeoxyglucose. The Belgian
      Society for Nuclear Medicine.
AB  - The purpose of these guidelines is to assist nuclear medicine practitioners in
      recommending, performing, interpreting, and reporting the results of brain
      perfusion SPECT studies using Tc-99m radiopharmaceuticals and brain metabolism
      PET studies using F-18 fluorodeoxyglucose (FDG). These guidelines have been
      adapted and extended from those produced by the Society of Nuclear Medicine (Juni
      et al., 1998) and the European Association of Nuclear Medicine by a Belgian group
      of experts in the field trained in neurology and/or nuclear medicine. Some
      indications are not universally approved (e.g. brain death), but largely
      supported by the literature. They have been included in these guidelines in order
      to provide recommendations and a standardised protocol.

PMID- 11851028
TI  - Serum lipid changes during anticonvulsive treatment serum lipids in epileptic
      children.
AB  - Serum lipid profile changes were investigated in 53 children receiving
      phenobarbital (n = 14), carbamazepine (n = 21), and valproic acid (n = 18) for
      their newly diagnosed seizure disorder. The patients were followed prospectively.
      Serum total cholesterol, high-density lipoprotein cholesterol, low-density
      lipoprotein cholesterol, and triglyceride concentrations increased after 3 months
      of treatment with carbamazepine and remained high after one year. Serum total
      cholesterol levels increased after 3 months of treatment with phenobarbital and
      remained high after one year. Serum lipid concentrations did not change during
      valproic acid therapy. Serum lipid profiles should be carefully monitored in
      children receiving enzyme inducing antiepileptic drugs.

PMID- 11851027
TI  - A double-blind clinical trial of mitoxantrone versus methylprednisolone in
      relapsing, secondary progressive multiple sclerosis.
AB  - A double-blind clinical trial of mitoxantrone versus methylprednisolone was
      performed in 49 patients with relapsing, secondary multiple sclerosis. Patients
      were randomized to receive 13 infusions of mitoxantrone 12 mg/m2 (n = 28), or 13
      infusions of 1 g of methylprednisolone (n = 21), over 32 months. Twenty-four
      patients completed the trial. There were no statistical differences between the
      two groups of patients at study entry. A significant improvement in the Expanded
      Disability Scale Score (EDSS) was observed in the mitoxantrone group after one
      year of treatment (p < 0.0022). The total number of relapses, the mean number of
      relapses/patient/year, and the total number of gadolinium-enhanced lesions on bi
      annual MRI scans were significantly decreased in the mitoxantrone group
      throughout the study period. Nausea, vomiting, and alopecia were more frequent in
      the mitoxantrone-treated patients. Mitoxantrone has a role in the treatment of MS
      patients with frequent exacerbations and rapid disease progression.

PMID- 11851030
TI  - Frontotemporal dementia: a clinical-pathological study.
AB  - We report a 44-year-old female patient without any familial history of dementia
      presenting with increasing disturbances in behaviour and language followed by a
      progressive cognitive deterioration. Neuropsychological evaluation revealed a
      significant impairment on frontal lobe tests. A brain PET scan disclosed a severe
      frontal hypometabolism. The tentative diagnosis of frontotemporal dementia was
      made. Her condition rapidly worsened and she died 2 years after the beginning of
      her disease. Gross examination of the brain showed a selective symmetrical
      atrophy of both frontal and anterior part of the temporal lobes. Microscopical
      examination revealed severe neuronal loss in the frontal and anterior temporal
      cortex associated with gliosis and microvascular spongiosis in the superficial
      cortical layers in the absence of any specific neuronal or glial inclusions.
      These neuropathological findings were consistent with the diagnosis of dementia
      lacking distinctive histology. We discuss the nosology of the frontotemporal
      dementias, the diagnostic value of PET scan, the recent genetical developments
      which strongly support the pathogenic role of tau and we emphasize the importance
      of immunohistochemical examination for a definite neuropathological diagnosis.

PMID- 11851029
TI  - Disappearance of central pain following iatrogenic stroke.
AB  - An exceptional case of long-standing central pain temporarily relieved by a focal
      stroke in the primary somatosensory area is reported. This case highlights the
      focal nature of central pain mechanisms and the possible value of selective
      subparietal leukotomies in the management of central pain.

PMID- 11851031
TI  - Longitudinal positron emission tomography study in a patient with presumed
      extracranial internal carotid dissection.

PMID- 11851032
TI  - Dorsal ulnar cutaneous neuropathy.

PMID- 11851033
TI  - Massive peripheral nerve hypertrophy in a patient with multifocal upper limb
      demyelinating neuropathy (Lewis-Sumner syndrome).

PMID- 11851034
TI  - [Incidental finding: left sided solid adrenal mass].
AB  - In a 49 year old male patient diagnostic evaluation of pneumonia performed by
      computed tomography revealed a left sided adrenal mass. The results of laboratory
      examination and MR-imaging of the adrenal glands suggested a hormonal inactive
      adrenal adenoma. Two years later, due to an increase in size, a surgical
      procedure was performed which revealed a gastrointestinal stromal tumor of the
      posterior gastric wall, rather than the suspected adrenal mass. Radiologic
      evaluation of adrenal masses and the clinical and pathologic characteristics of
      stromal tumors are discussed.

PMID- 11851035
TI  - [Incidental finding: left sided cystic adrenal mass].
AB  - Because of the widespread use of imaging techniques the incidental diagnosis of
      an adrenal mass without clinical symptoms and pathologic laboratory values
      becomes more and more common. To avoid unnecessary therapeutic interventions an
      intensive evaluation should take place including blood and urine testing as well
      as radiologic examination. An accurate assessment is often helpful in making the
      diagnosis of a benign process to avoid an invasive procedure and to determine the
      frequency and intensity of further controls. Nevertheless, in some cases the
      invasive approach is necessary because of an unclear situation or because of
      influences caused by the patient. An advantage is the possibility of laparoscopic
      intervention because of the minimal morbidity and until now no reported
      mortality.

PMID- 11851036
TI  - [Recurrent spontaneous hemorrhage in a patient with light chain immunocytoma].
AB  - The 48-year-old female patient was sent to our clinic for further evaluation of a
      spontaneous decrease of prothrombin- and prolongation of the bleeding-time. She
      presented in good conditions with an enlargement of cervical lymphnodes and the
      history of a monoclonal plasmacyte dyscrasia. The laboratory results revealed a
      pronounced decrease of prothrombin-time, a prolonged activated partial
      thromboplastin-time, a decrease of factor VII and X activity and a light chain
      paraprotein. The histological examination of the bone marrow led to the diagnosis
      of an immunocytoma and a medullar amyloidosis. For the aim of influencing the
      coagulopathy the patient was treated with chemotherapy. However, she developed
      severe bleedings. Further haemostaseological tests presented an amyloidosis
      associated decrease of factor VII and X, an acquired von Willebrands disease, an
      acquired thrombozytopathy and a lupus-like anticoagulans. Under substitution of
      factor VIII-von Willebrand-factor-complex and chemotherapeutic treatment a
      stabilisation over several years was achieved till the patient died due to an
      amyloid-associated acute pancreatitis.

PMID- 11851037
TI  - [Local and systemic symptoms after snake bite by a diamondback rattlesnake
      (Crotalus atrox)].
AB  - The incidence of snake bites grows more and more. The effects of the snake poison
      depend on the snake species. They can be cardio-, neuro-, myo-, tissue-, and/or
      cytotoxic, as well as hemorrhagically. In most cases a symptomatically therapy
      together with close controls of the labor parameters and a good monitoring is
      enough. Antivenom-therapy should be reserved for cases with strong indication.

PMID- 11851038
TI  - [Painful lipoma?].
AB  - The adiposis dolorosa (Dercum's disease) was described already in 1892. Many
      questions about its physiopathological mechanism are still unresolved.
      Presentation of a patient with this disease is reported, followed by a brief
      review of the literature, where the pathogenesis, the differential diagnosis and
      the therapeutical approaches of this syndrome are especially pointed out.

PMID- 11851039
TI  - [Madelung's disease (benign symmetric lipomatosis): still a mystery?].
AB  - The benign symmetric lipomatosis (Madelung's disease) is frequently associated
      with alcoholism. After 150 years of history, many questions about its
      physiopathological mechanism are still unresolved. Presentation of a patient with
      this rare condition is reported, followed by a review of the literature, where
      the pathogenesis, the differential diagnosis and the surgical approach of this
      syndrome are especially pointed out.

PMID- 11851040
TI  - [Chest pain in a 37-year-old Sikh].
AB  - Chest pain can be the only sign of osteomalacia. The case of a 37 years old
      patient from India, member of the religious group of the sikh, with vitamin D
      deficiency is presented. The disease developed as a consequence of reduced sun
      exposure (covering a substantial part of the body for ethnic reasons). The
      pathogenesis, clinical picture and implications for daily practice are discussed.

PMID- 11851044
TI  - [Urinary tract infections and antibiotic resistance].
AB  - Urinary tract infections (UTI) are diseases which differ considerably regarding
      pathogenesis, natural history and management. Complicated UTI as well as
      uncomplicated acute pyelonephritis in women are managed with pretherapy urine
      and, possibly, blood culture. This is not the case, however, with the most
      frequent UTI, acute uncomplicated cystitis in women. Empirical management
      strategies, without pretherapy culture, are well established and widely used. The
      treatment of choice is trimethoprim-sulfamethoxazole (TMP-SMZ) and
      fluoroquinolones. E. coli cause the vast majority of these infections, and
      resistance to TMP-SMZ has been observed to increase considerably during the last
      decade. Data from Europe and Switzerland regarding resistance of etiologic agents
      causing acute uncomplicated cystitis are very limited. Indeed, these empirical
      management strategies have resulted in poor microbiological information, since
      only selected groups of women with UTI undergo urine culture. Data derived from
      laboratory isolates usually lack the necessary clinical and epidemiological
      correlations. Preliminary data allow some estimates of the clinical and
      microbiological success rates when treating TMP-SMZ resistant uropathogens with
      TMP-SMZ. TMP-SMZ should probably no longer be used if the prevalence of TMP-SMZ
      resistance among uropathogens causing acute uncomplicated cystitis is 20% or
      higher. In these cases, a fluoroquinolone during three days, amoxicillin
      clavulanate during three to five days or nitrofurantoin during seven days should
      be given empirically. Non-antibiotic means of preventing UTI, such as increasing
      colonization resistance with lactobacilli, or the use of vaccines which provide
      inhibition of adherence of uropathogens to uroepithelial cells, show very
      promising experimental results. In order to survey and correct the value of our
      empirical strategies, more appropriate data on antimicrobial resistance and risk
      factors in the community are needed. This data can only be produced by a strong
      collaboration effort with networks of general practitioners.

PMID- 11851042
TI  - [Antibiotic resistance: infections of the upper respiratory tract and bronchi.
      When are antibiotics necessary?].
AB  - Antimicrobial resistance among respiratory tract pathogens has become an
      increasing problem worldwide during the last 10-20 years. The wide use of
      antimicrobial agents in ambulatory practice has contributed to the emergence and
      spread of antibiotic-resistant bacteria in the community, namely Streptococcus
      pneumoniae, Haemophilus influenzae and Moraxella catarrhalis. The pneumococcus
      has developed resistance to most antibiotics used for its treatment. Classes with
      important resistance problems include the beta-lactams, the macrolides, the
      lincosamides, trimethoprim-sulfamethoxazole, and the tetracyclines.
      Unfortunately, resistance to more than one class of antibiotics is common. In
      Haemophilus influenzae and Moraxella catarrhalis, resistance to beta-lactam
      antibiotics is the main concern currently. It is important to know the local
      resistance pattern of the most common respiratory tract pathogens in order to
      make reasonable recommendations for an empirical therapy for respiratory tract
      infection, when antibiotic therapy is indeed indicated.

PMID- 11851041
TI  - [Microbial resistance to antibiotics from the clinical viewpoint. Paradoxical
      therapy failures and the significance of pharmacokinetic-pharmacodynamic
      interactions in vivo].
AB  - Antimicrobial efficacy in vivo is not exclusively defined by the activity of an
      antibiotic as determined in the in vitro susceptibility test where constant
      inocula of log-phase bacteria are exposed to a steady concentration of drug for
      short periods of time in a well defined biochemical environment tailored to
      optimize antimicrobial activity. In vivo, many additional factors come into play
      which may be decisive for the clinical result of antimicrobial therapy.
      Clinically, high numbers of bacteria in various states of growth and metabolic
      activity are to be eliminated in an environment which may be unfavorable for
      antimicrobial activity. Low pH, low pO2, the presence of proteins, cell debris
      and biofilms, are all known to interfere with antimicrobial activity in vivo.
      Moreover, drug concentrations in vivo are fluctuating and vary greatly depending
      on a variety of pharmacokinetic factors. Finally, clinical treatment usually
      lasts for days. The impact of the pharmacokinetic profile of an antibiotic on its
      in vivo activity may be decisive. It is dependent on both, the type of drug in
      question and its target organisms. The time of supra-MIC concentrations appears
      to be the main parameter for the activity of macrolides, clindamycin, linezolide
      and betalactam antibiotics, particularly against gram-negative organisms. In
      contrast, peak concentrations and the AUC/MIC relationship are key parameters for
      the activity of aminoglycosides and fluoroquinolones. Regarding upcoming
      resistant bacterial strains, an as yet ill-defined mutation-prevention
      concentration has recently been discussed. Thus, in addition to the aim of
      eliminating target bacteria at the site of infection, in vivo concentrations of
      antibiotics may be important for both, the suppression of antimicrobial
      resistance and its epidemic spread. We are looking forward to prospective
      clinical trials to better understand the clinical relevance of the discussed
      phenomena.

PMID- 11851045
TI  - [Resistance problems in gastrointestinal infections].
AB  - A variety of world-wide resistance problems in bacterial gastrointestinal
      pathogens have emerged within the last decade. Particularly, antibiotics used to
      treat salmonella, campylobacter and Helicobacter pylori have lost their efficacy
      in a high proportion of isolates. Of major clinical significance is the
      resistance of H. pylori to metronidazole and clarithromycin, of Campylobacter
      spp. to fluoroquinolones and macrolides and of Salmonella spp. to
      fluoroquinolones and third generation cephalosporins. Of special concern is the
      spread of multiresistant isolates. Fortunately, in Clostridium difficile the
      resistance rate against metronidazole or vancomycin appears to be still low.
      Numerous investigations provided convincing evidence that the major source of
      emergence and dissemination of bacterial resistance is the use of antibiotics in
      food animals. This applies in particular to multiresistant strains of salmonella
      and campylobacter. A restricted use of antibiotics in the livestock is clearly
      warranted to control the unlimited development of resistance. The following
      recommendations should be considered in the care of infections with H. pylori,
      Campylobacter and Salmonella: 1) Treatment of H. pylori should be restricted to
      ulcer disease and gastric lymphoma. Eradication is not indicated in asymptomatic
      patients or patients with gastrointestinal pathologies that are not related to H.
      pylori. 2) Anti-H. pylori antibiotics should include metronidazole,
      clarithromycin, amoxicillin or tetracycline in combination of two of them. They
      should be used in short terms and in the recommended dosages together with proton
      pump inhibitors. If ulcers relapse after the first eradication, the resistance
      pattern should be determined. 3) In Campylobacter enterocolitis, antibiotics
      should be reserved for more severe cases. Resistance testing to exclude quinolone
      resistance is encouraged if antibiotics are considered. 4) In Salmonella
      gastroenteritis antibiotics do not significantly improve the course of infection.
      Their use should thus be restricted to patients which are at risk for
      disseminated disease including infants, elderly and immunosuppressed persons. 5)
      Since multiresistant Salmonella are common, resistance testing is highly
      recommended.

PMID- 11851046
TI  - [Significance of antibiotic resistance in treatment of soft tissue infections].
AB  - Soft tissue infections are common. The clinical spectrum includes infections of
      skin, subcutaneous tissue, and of deeper structures such as fascia and muscles.
      The pathogenesis of these infections is quite variable. Introduction of
      microorganisms through skin breaks or through trauma of other soft tissue is
      usually at the origin of such infections. Staphylococci, especially S. aureus, as
      well as streptococci, mainly group A streptococci cause most soft tissue
      infections. In immunocompromised patients or in particuluar circumstances gram
      negative bacteria may also be found to cause such infections. Occasionally,
      infections are polymicrobial. Given the predominance of gram-positive cocci,
      betalactam antibiotics with good antistaphylococcal activity are the drugs of
      choice for empiric treatment. Penicillins or cephalosporins that are stable
      against penicillinase should be chosen, since many staphylococci produce
      penicillinase. Over the course of the last 40 years staphylococci first became
      resistant against penicillin, and later developed resistance against methicillin.
      Methicillin-resistant S. aureus (MRSA) is now a significant problem worldwide.
      There continue to be major differences in the prevalence of MRSA between
      geographic regions. In areas with a high prevalence of methicillin resistance
      among S. aureus, empiric treatment of life-threatening soft tissue infections
      should include treatment with a glycopeptide (i.e. vancomycin or teicoplanin).
      New antibiotics such as oxazolidinones (i.e. linezolid) or
      quinupristin/dalfopristin are interesting alternatives to the glycopeptides in
      the treatment of soft tissue infections.

PMID- 11851047
TI  - [Antimicrobial resistance--consequences for ambulatory treatment of infections in
      children].
AB  - Increasing antimicrobial resistance among clinical isolates of Streptococcus
      pneumoniae calls for a revision of treatment strategies for pediatric infections,
      particularly for acute otitis media. Restrictive use of antimicrobials is the key
      strategy for slowing the spread of resistances. Before initiation of
      antimicrobial therapy, suspected bacterial infections should be confirmed
      clinically (e.g. by observation of the natural evolution) or microbiologically.
      For acute otitis media, oral amoxicillin remains the drug of choice because of
      superior middle ear pharmacokinetics and pharmacodynamics. Treatment failure
      caused by resistance of the infecting pneumococcus can be overcome be increasing
      the dose, and not by switching to another class of antibiotics (e.g.,
      cephalosporin, macrolide, cotrimoxazole), which is less likely to achieve middle
      ear eradication a priori. Widespread macrolide resistance among isolates of S.
      pneumoniae precludes the use of this class of antimicrobials for empiric therapy
      of community-acquired pneumonia in children. Aminopenicillins are preferred
      because of their rapidly bactericidal activity against the most common organisms
      causing potentially progressive pneumonia in children.

PMID- 11851048
TI  - [Mechanisms of antibiotic resistance].
AB  - Antibiotics interfere with structural and regulatory elements of bacterial cells
      leading to growth arrest or cell death. Bacteria have evolved a variety of
      strategies to overcome the effects of antibiotics. Examples are enzymatic
      destruction, alteration of the target, efflux and permeability changes.
      Resistance towards the same substance can be mediated by several mechanisms.
      Efflux pumps can probably act as mediators of higher resistance development.
      Alteration of common targets can lead to cross-resistance against several classes
      of antibiotics. Genetic events, such as point mutations, transfer of plasmids and
      gen regulation, can mediate a rapid emergence of resistance. Therefore,
      substances like rifampicin should be only used in combination with other drugs.
      Accumulation of resistance genes under common regulatory control in integrons
      induces co-resistance against substances of different specificity. Detailed
      knowledge of resistance mechanisms, their evolution and dynamics is important for
      a rational use of antibiotics and other strategies against antibiotic resistance.

PMID- 11851049
TI  - [Successful strategies against increasing antibiotic resistance].
AB  - The development of antibiotic resistance, known since the early days of
      antibiotic therapy, has accelerated in recent years and makes a postantibiotic
      era a realistic future scenario. The battle against increasingly resistant
      strains has become a major concern for infectious disease and infection control
      specialists worldwide. The issue has now gained heightened awareness among
      physicians in all specialties and the public, and has become a challenge to
      hospital leadership. Detailed evidence about the causes and conditions of
      antibiotic resistance is accumulating, but the main axes have been known for some
      time: overuse and misuse of antibiotic therapy and transmission of multiresistant
      pathogens or genetic material between humans. Selection pressure by the
      systematic use of antibiotics as growth promoters in animal husbandry and the
      resulting transmission by the food chain is an additional important cause. This
      overview presents the most promising strategies to contain further resistance
      spread and hopefully inverse the current trend.

PMID- 11851050
TI  - [Adverse drug reaction and rational use of levofloxacin: a prospective study].
AB  - OBJECTIVE: To study the rate of adverse drug reaction(ADR) and the rational use
      of levofloxacin among in-patients. METHOD: All in-patients treated with
      levofloxacin were prospectively observed in 7 hospitals of Beijing. RESULTS: One
      hundred and five ADR cases were found in 2,661 patients injected with
      levofloxacin. The ADR rate was 3.9% while 4.8% of them were classified as severe
      cases. All severe ADR cases had a nature of double infections. The ADR occurrence
      was related to older age, irrational drug use, combined medicine and allergic
      history. The rate of levofloxacin irrational use was 19.9%, especially in the
      elderly population, due to too long or too short course of treatments.
      CONCLUSION: Levofloxacin is viewed as a safe injection in clinical practice,
      however, combined medicine and elderly patients should be paid more attention
      when on administration of this medication. The irrational use of levofloxacin was
      recognized as one of the main reasons causing the increase of ADR.

PMID- 11851052
TI  - [Application and time-effect analysis of antibiotics among neonatal pneumonia
      treatment].
AB  - OBJECTIVE: To understand the results of antibiotics use in curing neonatal
      pneumonia and to evaluate the time-effect of different drugs. METHODS: Through
      stratified sampling, all the hospitalized cases of neonatal pneumonia from 5
      hospitals with different levels in Hunan province in five years were
      retrospectively studied. Analysis of time-effect for different antibiotics was
      done through Kaplan-Meier. RESULTS: Twenty-six kinds of anti-bacterium drugs were
      used in 685 cases of neonatal pneumonia, among which penicillin and ampicillin
      were mostly used but cephalosporins also became one of the main drugs used in
      treating neonatal pneumonia. Most cases were discovered (51.1%) using two kinds
      of antibiotics during the course of diseases through time-effect analysis. We
      found the effect of penicillin was better than others in treating neonatal
      pneumonia when used as basic medicine. It was not desirable to use two or more
      medicines at the beginning of the treatment. CONCLUSION: Penicillin and
      ampicillin were still the main drugs used in treating neonatal pneumonia but more
      cephalosporins were used than ever. The blindness in applying antibiotics should
      be recovered. From Kaplan-Meier analysis, we could better understand and evaluate
      the time-effects of different drug treatments.

PMID- 11851051
TI  - [Therapeutic trial on function bandage for military training injuries].
AB  - OBJECTIVE: To evaluate therapeutic effectiveness of "Tianniansu" function bandage
      used for military training injuries (MTI). METHODS: In a randomized tri-blind
      controlled trial, recruits of all soft tissue injuries and stress fracture (SF)
      who took part in basic training in 1998 were separated into two groups--A and B
      with comparability, except the use of bandage. After close follow up on weekly
      base, part of the patents were subjected by ECT pre and post therapy. RESULTS:
      Effective rates of bandage A and B on treating soft tissue injuries were 66.7%
      and 86.4%, respectively. However, in terms of symptoms, detumescence effect of
      bandage B showed milder than that of A. The effective rate of bandage A and B in
      treating SF were 67.2% and 75.0%, respectively, but statistically not
      significant. The treatment effect in 26 injured tibias evaluated by bone
      scintigraphy pre and post treatment showed that the degree of osteogen injury
      after treatment was not significantly improved. CONCLUSION: "Tianniansu" function
      bandage had significant effect on treating soft tissue injuries, but did not have
      effect in treating SF.

PMID- 11851053
TI  - [Study on drug use in elderly outpatients in Beijing].
AB  - OBJECTIVE: To understand the situation of drug use, drug request, combination of
      drugs and daily drug dose (DDD) among elderly patients, to provide scientific
      evidences for safely, effectively, economically and rationally on disease
      prevention and improving the quality of life of the elderly patients. METHODS: A
      2-year(1998-1999) prescriptions database which was set up according to different
      departments of consultation, patient age, sex, consultation date, and name of
      drugs, dosage was used for the study. Prescriptions were randomly selected on 3-4
      days in every month, from 22 hospitals in Beijing. FOXPRO software was used for
      statistics and analyses. Information of elderly patients (> or = 60 year) on
      status of drug use, was collected and compared with general patients. RESULTS:
      The proportion of elderly patients' prescription was 19.9%, with an average
      number of drugs prescribed in elderly patients 2.71, which was 0.27 higher than
      that of the general patients. Proportion of injections per every hundred elderly
      patients prescriptions was 18.4%. The major kinds of drugs were those related to
      cardiovasculars and vitamins. The most frequent drug was vitamin E nicotinate.
      DDD on elderly patients was lower than that defined by WHO and drug instruction,
      but higher than that of the general patients during the same period and was
      increasing. Daily dose of anti-hypertensions was also higher. The rate of
      consultation for cardiovascular diseases was high. The ratio of drugs in
      accordance with national essential drug list was 87.5%. CONCLUSIONS: The rates of
      elderly patients' prescription, average number of drugs per prescription,
      proportion of injections and DDD were high. The rational drug use on elderly
      patients should be given more concerns.

PMID- 11851054
TI  - [Study on the compliance of antihypertensive drugs in patients with
      hypertension].
AB  - OBJECTIVE: To study the compliance of antihypertensive drugs and its related
      factors in inpatients and outpatients patients with hypertension. METHOD:
      Clinical data of 816 inpatients and 497 outpatients were reviewed to study the
      compliance of antihypertensive drugs and related factors as well as to
      investigate the utilization of anti-hypertensive medicament, the incidence of the
      side-effect of the medication and to explore the difference of the blood pressure
      control between the compliant group and the uncompliant group. RESULTS: The main
      risk factors of the hypertensive patients were in the order as: disorder of
      lipometabolism, smoking, left ventricular hypertrophy (LVH) and Diabetes
      mellitus. Sixty point nine percent of the inpatients were followed up. The
      incidences of compliance were 63.4% in the inpatients, 77.3% when being
      discharged, and 43.7% in the outpatients. The cause of uncompliance were as
      follows: side-effect of the medication, failure to control BP, financial
      problems, etc. Data gathered during follow up period, it was found the side
      effect of the calcium antagonist and the diuretics improved palpably. Those
      compliers controlled their BP well, while little fluctuation of BP was observed.
      However, the uncompliers showed different pictures, and the range of fluctuation
      of BP was large. CONCLUSIONS: The compliance of the medicament was best among the
      outpatients to the discharge order, and the compliance of the outpatients was the
      worst.

PMID- 11851056
TI  - [Relationship between epidemiology of HIV-1 infection and HIV-1 subtypes in
      Fujian province].
AB  - OBJECTIVE: To explore the relationship of AIDS epidemic and HIV-1 subtype in
      Fujian province of China based on molecular findings. METHODS: HIV-1 infected
      persons and patient with AIDS (HIV/AIDS) were identified by AIDS surveillance
      project in the province. AIDS epidemic situation was estimated by related data
      collected from the HIV/AIDS cases. HIV-1 C2-V3 region amplified from the PBMC DNA
      of HIV/AIDS cases was analysed by nucleotide sequencing to identified HIV-1
      subtype. RESULTS: One hundred and eighty-eight cases of HIV/AIDS were found from
      1987 to the end of 2000. Among 59 AIDS cases, 53 had died. HIV infection through
      heterosexual contacts took up 65.4%, including 44.1% of them infected abroad. Out
      of them, 83.1% were infected in Southeast Asia. Thirty-nine point nine percentage
      of the total HIV(+) were infected in China, while 9.0% were infected through
      blood transmission. Sequence analysis from 41 specimens showed that there were 4
      kinds of HIV-1 subtypes, including A, B, C and E. Subtype E took up 75.6%
      (31/41), all infected by heterosexual contacts; subtype B taking up 17.1% (7/41)
      with most of them infected through blood transmission; subtype A and C were seen
      only 1 and 2 cases respectively. Gene divergence of innergroup of subtypes E was
      12.245% +/- 3.894%, while subtype B was 10.762% +/- 2.707%. The high divergence
      of subtype E could be attributed to the region and time of infection. CONCLUSION:
      HIV prevalent rate has been increasing in Fujian with major transmission route of
      heterosexual contact. The dominant strain of HIV-1 was subtype E.

PMID- 11851057
TI  - [Genetic subtyping of HIV-1 in Liaoning province of China].
AB  - OBJECTIVE: To study the prevalence of HIV-1 in Liaoning province of China.
      METHODS: Nuclear acids were extracted from blood samples of 16 HIV-1 infected
      individuals collected locally in Liaoning province of China from Jun. 1997 to
      Dec. 2000. The 0.7 kb or 1.2 kb segments of HIV-1 env gene were amplified using
      nested-PCR and the HIV-1 genetic subtypes were then assayed by heteroduplex
      mobility assay. RESULTS: Fifteen of 16 samples were positive by PCR amplification
      of HIV-1 env region and samples were found to be genetic subtype A,B',C,E. The
      proportion due to sexual transmission in all HIV infection was 31.25% (5/15),
      among which subtype B' (3/5) was the majority. A man who returned from Africa
      together with his spouse both had type A (2/5) infection. Intravenous drug users
      (IDUs) took up 31.25% (5/15) of all the HIV infections. Subtype C (2/4) and E
      were predominant among intravenous drug users. However, there was one IDU with
      subtype B or E. Nearly all blood recipients and blood donors were B' (4/5) except
      one with C. CONCLUSION: There have been several subtypes of HIV-1 existed in
      Liaoning province, demonstrating the complexity of HIV epidemology in Liaoning
      province and the difficulty conducting prevention and treatment.

PMID- 11851055
TI  - [Evaluation on the effect of cardiovascular prevention program in Fangshan,
      Beijing].
AB  - OBJECTIVE: To evaluate the effect of cardiovascular prevention program in
      Fangshan, Beijing (BFCP) from 1991-1999. METHODS: BFCP was a comprehensive
      community trial covering 120,000 residents in five communities, including three
      as intervention communities (IC), and two as control communities (CC), in
      Fangshan, suburb of Beijing. The program was implemented under both population
      and high risk individual strategies, focusing on health education and
      hypertension control. The main intervention measures were as follows: (1) network
      setup; (2) health education and promotion; (3) health professional training; (4)
      detection and management of hypertensive patients. RESULTS: Baseline, midterm and
      final cross-sectional surveys were conducted in the year 1991, 1995 and 1999,
      respectively. After 9-year intervention, improvement was found in population of
      IC versus CC (P < 0.01 or P < 0.05) for knowledge, attitude and behavior of CVD
      prevention, awareness on hypertension, treatment and control rates, as well as
      the quantity of dietary intake of protein, potassium and calcium. Risk factors
      such as systolic blood pressure, diastolic blood pressure, rates of smoking and
      alcohol drinking declined in the population in IC versus CC (P < 0.01). The
      average morbidity and mortality of stroke were 18.7% (u = 2.81, P < 0.01) and
      17.7% (u = 2.91, P < 0.01), significantly lower in the IC versus CC. No
      significant difference was identified on the morbidity and mortality of coronary
      heart diseases between IC and CC. CONCLUSION: The comprehensive community
      prevention approach was feasible and effective in the prevention and control of
      cardiovascular diseases in rural populations in China.

PMID- 11851058
TI  - [The relationship between angiotensin converting enzyme gene polymorphism and
      risk factors for cerebral infarct].
AB  - OBJECTIVE: To explore the relationship between angiotensin converting enzyme
      (ACE) gene polymorphism and risk factors of cerebral infarct (CI) in Chinese Han
      nationality. METHODS: One hundred and sixty-five cases with cerebral infarct, 101
      cases of essential hypertension patients with 106 normal persons in Chinese Han
      serving as controls were detected using polymorase chain reaction (PCR) and
      genetic methods. ACE contents in serum were measured by colorimetric method. Risk
      factors of cerebral infarct were assessed by standard questionnaire, physical
      examination and blood tests. RESULTS: ACE DD genotype appeared more common in
      patients of cerebral infarct when comparing with essential hypertension groups
      (0.43 versus 0.31, chi 2 = 4.03, P < 0.05) and normal controls (0.43 versus 0.17,
      chi 2 = 19.86, P < 0.01). D:I allele frequency appeared to be 0.66:0.34 in
      cerebral infarct patients and 0.41:0.59 in controls (chi 2 = 32.85, P < 0.01). In
      basal ganglia infarct and thalamus infarct groups, ACE DD genotype and allele
      ratio distribution were remarkably different to that in normal subjects (chi 2 =
      18.30, 12.41, P < 0.01). The mean levels of serum in cerebral and hypertension
      were higher than in normal controls (F = 2,240.06, P < 0.01), and serum ACE
      activity in ACE DD genotype was significantly higher than that in ACE DI and II
      genotype in cerebral group (F = 8.83, P < 0.01). CONCLUSIONS: The ACE gene
      deletion polymorphism might serve as an independent risk factor for cerebral
      infarct in Chinese Han nationality while circulation ACE activity might be
      related to gene deletion polymorphism.

PMID- 11851059
TI  - [Nested case-control study on the risk factors of colorectal cancer].
AB  - OBJECTIVE: To investigate the risk factors of colorectal cancer. METHODS: A
      nested case-control study was conducted based on a cohort of 64,693 subjects in
      Jiashan county, Zhejiang, China. One hundred and ninety-six cases of colorectal
      cancer were detected during a follow-up program for 10 years. Nine hundred and
      eighty non-colorectal cancer subjects were randomly selected from the cohort as
      controls. Univariate analysis and mutivariate non-conditional logistic regression
      were used to analyse associations between the exposure factors and colorectal
      cancer. RESULTS: The age of case group was significantly older than that of the
      control group. Moreover, the age at diagnose of colon cancer was significantly
      older than that of the rectal cancer. Other than age, the final regression model
      showed that mucous blood stool history and colon polyp history were significantly
      associated with colon cancer (OR = 2.961, 95% CI:1.202-7.298 and 8.941, 95%
      CI:1.820-43.926, respectively) while mixed sources of drinking water was found to
      be associated with rectal cancer with a OR value of 1.823 (95% CI:1.024-3.247).
      CONCLUSION: The risk factors of colon cancer were different from that of the
      rectal cancer. Age was an important factor influencing the incidence of both
      colon cancer and rectal cancer. Mucous blood stool history and colon polyp
      history were associated with colon cancer, while drinking mixed water was closely
      associated with rectal cancer.

PMID- 11851060
TI  - [A case-control study on the risk factors of esophageal cancer in Jieyang City of
      Guangdong in China].
AB  - OBJECTIVE: To study the risk factors of esophageal cancer in Jieyang city of
      Guangdong province. METHODS: Two hundred and fourteen cases with pathological
      diagnosis of esophageal cancer were recruited at Jieyang Municipal People's
      Hospital in 1999. Two hundred and fourteen controls were selected from healthy
      residents matched with sex, age and residential places (town) of the cases. All
      cases and controls had resided in Jieyang city for over 20 years and were studied
      through a uniformed questionnaire. Non-conditional logistic regression was used
      for multivariate analysis. RESULTS: The important risk factors were over-hot tea
      drinking habit (OR:1.39-3.74), fast eating (OR:1.54-4.10), animal oil (OR:3.57
      42.03) and meat consumption (OR:1.36-5.05) while the protective factors were tap
      water (OR:0.13-0.51) drinking habil for over 20 years. Histories of smoking and
      family esophageal cancer were not significantly correlated with esophageal
      cancer. CONCLUSION: The risk factors revealed in this study were commonly exposed
      to the residents of Jieyang city. Most of the factors were in agreement to the
      results from other similar studies, but the factors of animal oil and meat were
      unique in this study, which called for further studies.

PMID- 11851061
TI  - [A survey of the current status and distribution of cataract in the elderly].
AB  - OBJECTIVE: To study the current status and distribution of cataract in the ageing
      population. METHODS: A total number of 8,252 elderly aged 60 years and above in
      the urban and rural areas of Beijing, Shanghai, Guangzhou, Chengdu, Xi'an and
      Shenyang were studied, using cluster random sampling methods. RESULTS: The crude
      and adjusted rates of cataract prevalence in the elderly were found to be 46.8%
      and 42.8% respectively. However, the self-reported crude prevalence was 19.7%
      with only 42.1% of that shown by medical examination. The prevalence rates
      increased with ageing (P < 0.01), to have shown 27.9%, 41.3%, 53.2%, 67.5% and
      68.0% in the age groups of 60-, 65-, 70-, 75-, 80-, 85- years old respectively (P
      < 0.01). There was difference in the prevalence among areas, with highest (77.9%)
      in the urban areas in Guangzhou and in the rural areas in Beijing (67.3%) (P <
      0.01). The prevalence differed in gender as well: higher in women (49.1%,
      adjusted) than in men (35.6%, adjusted). Logistic regression analysis showed that
      the crude prevalence was correlated with ageing, profession and area (P
      respective < 0.01). CONCLUSION: The prevalence of cataract was high in the
      elderly and increased with ageing with differences in areas, and professions. It
      was low when self-reporting shown by medical examination, suggesting prevention
      and treatment of cataract in the elderly be strengthened.

PMID- 11851062
TI  - [Analysis on the genetics of Hantavirus S85-46 isolated from Sichuan province].
AB  - OBJECTIVE: To understand the molecular and epidemic characteristics of Hantavirus
      S85-46 isolated from Sichuan province. METHODS: RT-PCR products were amplified
      from S85-46 virus infected cells, cloned into T vector, sequenced and analyzed
      using DNASTAR software. RESULTS: The homology of M segment of S85-46 strain and
      HTN type strain varied from 84.1%-99.7%, compared to 70.4%-70.9% with SEO
      strains. This result indicated that S85-46 strain belonged to hantavirus. The
      nucleotide sequence analyses indicated that S85-46 strain, LR1 strain and 76-118
      strain were highly homologous. The two latter strains were isolated from Shaanxi
      province of China and South Korea respectively, which were far from Sichuan
      province of China. The nucleotide sequence analyses of S segment was similar to M
      segment. CONCLUSION: The epidemic strains isolated from different regions may
      have been highly homologous.

PMID- 11851063
TI  - [An epidemiological study on the risk factors of irritable bowel syndrome in
      Zhanjiang, Guangdong province].
AB  - OBJECTIVE: To assess the risk factors in the pathogenicity of irritable bouel
      syndrome(IBS) in Zhanjiang city. METHODS: Two hundred and seven IBS patients were
      randomly selected and compared with "healthy" people diagnosed in the same
      hospital during the same period. Roles of major risk factors to IBS were studied
      through using a case-control study. RESULTS: Family history of hysteria or mental
      disease and vegetorsis was closely related to IBS, with ORs 3 and 4 respectively.
      There was alse close relationship between IBS and psychic trauma, often taking
      antibiotics, tension at work and eating sweet potato or cassava, with ORs between
      1 and 2. CONCLUSION: Our investigation suggested that the six major risk factors
      mentioned above played important roles in the progression of IBS in Zhanjiang
      city.

PMID- 11851064
TI  - [Study on the effects of increased iodized salt intake on the incidence of
      thyroid diseases].
AB  - OBJECTIVE: To study the annual incidence of thyroid diseases before and after the
      increase of iodized salt intake. METHOD: A total of 26,010 persons were examined
      from mid August to the end of December in 1999. RESULTS: 1. Three hundred and ten
      patients of thyroid diseases were identified from 1990 to July 1999. One hundred
      and eighty-three patients were diagnosed after iodine supplementation. 2. The
      constitution of thyroid diseases had changed significantly regarding the increase
      of hyperthyroidism, simple goiter and thyroid nodule. 3. Fifty-five patients with
      hyperthyroidism including 39 patients (70.91%) receiving iodine supplementation
      were diagnosed. The average annual incidence of hyperthyroidism after iodine
      supplementation was 36.87 per 100,000, a three-time increase as compared with
      that before iodine supplementation. The incidence of hyperthyroidism began to
      show a significant rise in 1996. The year with highest annual incidence was 1997,
      remaining at high level after supplying iodized salt. Since then the annual
      relative risk for hyperthyroidism had been increasing. CONCLUSION: The number of
      patients with thyroid diseases showed a significant increase after mass iodine
      supplement. At the same time, the spectrum of thyroid diseases had also changed.
      Iodized salt intake and the incidence of hyperthyroidism showed a significant
      correlation. However, the typical model of the change of disease patterns
      incidence needs further study.

PMID- 11851065
TI  - Are epidemiologists becoming victims of the success of their discipline?

PMID- 11851066
TI  - A better understanding of health issues through population-based surveillance.
      Why surveys?

PMID- 11851068
TI  - Assessment of physical activity in population surveys.

PMID- 11851069
TI  - Methods of outbreak investigation in the "era of bacteriology" 1880-1920.
AB  - The advent of bacteriological methods in the later 19th century has been seen, on
      the examples of America and Germany, to have been followed by a new laboratory
      based, contact-tracing method of investigating outbreaks of epidemic disease. In
      Britain, however, this new approach never took firm root, and practising
      epidemiologists continued to follow an observational and deductive tradition in
      field investigations, rejecting any primary dependence on bacteriological
      methods. Alongside this persistent observational practice, there emerged a new
      statistical approach, based in Pearsonian biometrics, which allied itself with
      experimental laboratory techniques to develop a more systematic, theoretical
      trajectory for explaining disease outbreaks in the years after World War I.

PMID- 11851067
TI  - A new look at the relation of epidemiology and bacteriology at the turn of the
      20th century.

PMID- 11851070
TI  - Lessons for surveillance in the 21st century: a historical perspective from the
      past five millennia.
AB  - This paper reviews some major epidemics in the past 5,000 years in human history
      and derives 12 lessons in the context of epidemiologic surveillance. The
      corresponding 12 challenges proposed in this paper could be used to guide us in
      building a better and more comprehensive surveillance system in the 21st century.
      This will be achieved by: continuing the evolvement and improvement of
      surveillance; maintaining on an ongoing basis; being systematic; being population
      based; including risk and intervention indicators in the data base; more
      efficient data analysis; stimulating etiologic research; improving forecasting
      capability; linking to development of intervention; evaluating the intervention;
      better ways of information dissemination; and dissemination without prejudice.

PMID- 11851071
TI  - Evaluating composite health measures using Rasch modelling: an illustrative
      example.
AB  - OBJECTIVES: The purpose of the present article is to elucidate the opportunities
      provided by Rasch modelling in epidemiology and public health research in order
      to evaluate composite measures of health. METHODS: The article gives a review of
      Rasch modelling in conjunction with illustrative examples based on adolescent
      survey data. RESULTS: The article demonstrates how the Rasch-model enables
      examinations of the way items work across different samples/subgroups, e.g.,
      detection of possible differential item functioning. CONCLUSIONS: It is concluded
      that Rasch modelling may serve as a useful tool in the evaluation and the
      development of composite health measures intended to be used in epidemiology and
      public health research.

PMID- 11851072
TI  - [Does the structure of medical services affect the proportion of death in
      hospitals? An ecological analysis in the mobility regions of Switzerland?].
AB  - OBJECTIVES: With the discussion about measures to reduce over-capacities in the
      health services in mind, we examined the influence of medical supply structures
      and services on hospital utilisation directly before death. METHODS: Based on the
      specification of the place of dying from the death certificates, we determined
      the proportions of deaths in hospitals in an ecological study. We analysed deaths
      of persons above age 65 in each of the 106 mobility regions of Switzerland in the
      years 1979 to 1980. RESULTS: The proportion of deaths occurring in hospitals
      varied between 27% and 81%. Despite missing data regarding stationary and
      ambulatory care services, more than half of the variance could be explained by
      means of a multivariate regression analysis. Our results imply an inverse
      relation between the proportion of deaths in the hospital and the number of
      consultations provided by primary care physicians, as well as the number of
      nursing home beds. Further, we observe a direct relation to the number of
      hospital beds in a region. All indicators are calculated per inhabitant.
      CONCLUSIONS: In health care supply planning, such systematic associations should
      be taken into account. We recommend to analyse regularly interregional
      differences in supply and outcome of medical performances with the best available
      data.

PMID- 11851073
TI  - Sickness certification in primary care.
AB  - OBJECTIVES: Sickness certification is a common task, which is however
      insufficiently studied. Our objective was to describe, prospectively,
      prescription practices in sickness certification by primary care physicians.
      METHODS: We recorded patients receiving a sickness certificate during a six-week
      study period. The main outcome measures were: duration of sick-leave according to
      age, profession, diagnosis, nationality, somatic, or psychiatric comorbidity as
      well as co-factors related to the familial or professional environment. RESULTS:
      Out of a total of 6,433 consultations, 602 patients received a sickness
      certification, and in 56% of these, sick-leave duration was > or = 6 days.
      Multivariate analysis showed that presence of co-morbidity and co-factors,
      greater age and musculoskeletal, cardiovascular, psychiatric disease and injury
      were independently associated with a longer sickness certification duration.
      CONCLUSIONS: Sickness certification is a complex task which entails not only
      consideration of the diagnosis but also of other factors such as co-morbidity, as
      well as familial and professional environment. Physicians should be aware of
      these elements and of situations, which might lead to a longer sick-leave period.

PMID- 11851074
TI  - Stages of change for perceived stress in a Swiss population sample: an
      explorative study.
AB  - OBJECTIVES: Data from a cross-sectional survey of the Swiss general population
      were used in an explorative attempt to apply the transtheoretical model of
      behavioural change to perceived stress. METHODS: The sample comprised 575
      respondents who reported having experienced stressful situations in the previous
      month. Other variables assessed included gender, age, education, reported
      symptoms, and three constructs representing stages and processes of change as
      well as self-efficacy. RESULTS: Findings indicated that (1) about one third of
      respondents appeared to cope successfully with the stressful situations they
      experienced, one third intended to do so, while one quarter appeared to have no
      intention of managing their stress more effectively. (2) There was no difference
      in stage of change distribution by gender or age, while those with higher
      education were more frequently represented in the latter stages than those with
      lower education. (3) Those in the maintenance stage reported significantly less
      symptoms than others. CONCLUSIONS: We conclude that the assessment of readiness
      to change could be of valuable support in designing stage-specific interventions
      in the area of stress management.

PMID- 11851075
TI  - Sense of coherence in adolescents.
AB  - OBJECTIVES: The course of sense of coherence (SOC) in adolescents over an 18
      month-period and the correlation between individual variability in the SOC scale
      scores and physical and psychological symptoms were examined. METHODS: A sample
      of 341 students from two Swiss senior high schools were investigated by means of
      questionnaires three times over a period of 18 months. The questionnaire
      comprised the SOC scale (SOC-13) and measures of physical and psychological
      impairment. RESULTS: Male adolescents had a significantly higher SOC mean score
      than females. Significant negative correlations between the SOC and the symptom
      scales were found in both genders. Higher symptom scores correlated with a
      greater variability of the SOC scores. Independent of their sex, individuals with
      a high SOC score at t1 showed less variability in the SOC values over time than
      individuals with low SOC scores. In adolescents who revealed low symptom scores
      the SOC scale scores almost reached levels seen in adults and remained relatively
      stable over time. CONCLUSIONS: The results suggest a certain degree of stability
      of SOC in middle to late adolescence.

PMID- 11851076
TI  - [Urine incontinence in childhood; the importance of a good micturition history].
AB  - Four children, three girls aged 9, 5.5 and 6.5 years, and a boy aged 8 years,
      suffered from urinary incontinence. The underlying conditions, urge syndrome with
      urge incontinence, ectopic ureter, meatus stenosis, and pelvic floor dysfunction,
      respectively, were identified and treated, after which the children were no
      longer incontinent. Diurnal incontinence is present in 2-3% of 7-year-olds.
      Incontinence is accompanied by recurrent urinary tract infections and
      vesicoureteric reflux in 40% of cases. A combination of these two disorders can
      lead to impaired renal function. Especially in girls, involuntary urine loss is
      usually based on dysfunctional voiding, a non-neurogenic coordination problem
      between the detrusor muscle of the bladder and the pelvic floor. A careful
      history is the most important tool in reaching the correct diagnosis.

PMID- 11851077
TI  - [Resection of liver metastasis: higher chance of survival].
AB  - In patients with colorectal liver metastases, resection is the only intentionally
      curative therapy. It is stated that follow-up after a resection of primary
      colorectal malignancies does not favourably influence patient outcome. However,
      follow-up can identify 12% of patients with isolated liver metastases in whom
      liver resection should be performed. One third of these patients can be cured by
      liver surgery. In general, medical care is provided for lower chances of survival
      and freedom of disease. Local ablative therapies are probably useful, but need to
      be evaluated in a randomised trial. Tumour progression of hepatocellular
      carcinomas in patients, during the long waiting time for liver transplantation,
      necessitates the use of radiofrequency ablation. Minimally invasive techniques
      for liver resections seem to be promising but need to be evaluated before they
      can be more widely applied.

PMID- 11851078
TI  - [Chronic venous insufficiency].
AB  - Chronic venous insufficiency (CVI) is a complex of symptoms occurring on the
      lower leg, which includes varicose veins, oedema, pigmentation and venous leg
      ulceration. Most patients have severe complaints, which result in a high medical
      consumption, mainly due to venous leg ulceration. CVI is caused by a
      decompensation of the venous system together with reflux in the superficial, deep
      and/or perforating veins of the lower leg in supine position. The exact
      pathogenesis of the skin symptoms is still largely unclear. An increased walking
      venous pressure induces macrocirculatory and microcirculatory changes such as
      dermal pericapillary fibrin cuffs, leukocyte accumulation and the activation of
      cytokines. CVI can be treated in several ways: compression therapy, if needs be
      combined with sclerotherapy or surgery, or with supportive medication.

PMID- 11851079
TI  - [Methods to improve patient compliance in the use of antidepressants].
AB  - Compliance during treatment with antidepressants is important, yet about half of
      the patients stop using antidepressive medication within 3 months. A structured
      treatment programme, in which the patient actively participates, with extensive
      education, surveillance of side effects and compliance, simple regimes, improving
      problem-solving behaviour and eventually engaging and educating family members
      and friends can improve compliance. This has been demonstrated in published
      studies. Research has shown that interventions that enhance compliance can lead
      to a better outcome of the depression.

PMID- 11851080
TI  - [Sponsored research, authorship and accountability; declarations by authors of
      their independence regarding publications].
AB  - The editorial board of the Nederlands Tijdschrift voor Geneeskunde (Dutch Journal
      of Medicine) has decided to disclose at the end of each article conflicts of
      interest (financial and otherwise), the sponsor of the research or its
      publication, and whether the authors were independent in their investigations,
      analysis and reporting of the data.

PMID- 11851081
TI  - [Diagnostic image (74) A woman with stomach cramps and vomiting].
AB  - In a 53-year-old woman with abdominal pain, nausea and vomitus lasting for a
      month and leading to weight loss, abdominal CT showed abdominal spigelian hernia.

PMID- 11851082
TI  - [Partial liver resections: mortality, morbidity and risk factors for
      postoperative complications in 133 patients/137 operations; Utrecht University
      Medical Center 1991/2000].
AB  - OBJECTIVE: Evaluation of the results of partial liver resections for both benign
      and malignant abnormalities and the identification of risk factors for the
      development of complications. DESIGN: Descriptive, retrospective. METHOD: All
      consecutive partial liver resections performed between January 1991 and October
      2000 at the University Medical Centre Utrecht, the Netherlands, were reviewed for
      preoperative, peroperative and postoperative parameters. Risk factors were
      determined by means of a univariate analysis and a multiple logistic regression
      analysis. The 5-year survival rates were calculated using the Kaplan-Meier
      method. RESULTS: A total of 133 patients (71 men and 62 women; median age: 58
      years (range: 17-79)) underwent 137 hepatic resections for benign (n = 29) and
      malignant (n = 108) liver abnormalities. In total, 74 procedures (54%) were
      considered to be major hepatic resections and blood transfusion was required in
      97 patients (71%). A total of 43 complications was observed in 32 patients
      (32/137; 23%). Eight patients died as a result of postoperative complications
      (8/137; 5.8%). Independent risk factors associated with the development of major
      complications were a major resection (OR: 3.6) and more than 2 peroperative units
      of packed cells (OR: 5.0). The principal indication for liver resection were
      colorectal metastases (n = 69). The 5-year survival rate after liver resection
      for colorectal metastases was 38% (95% CI: range 21-54) with a 5-year disease
      free survival rate of 25% (range 10-41). The postoperative mortality in this
      group was 2.9%. CONCLUSION: After partial liver resection for benign and
      malignant lesions the mortality was 5.8% and the morbidity 23%. The risk of
      postoperative morbidity was related to the number of peroperative units of packed
      cells and the extent of the resection.

PMID- 11851083
TI  - [The treatment of colorectal liver metastases: good 5 year survival chance after
      partial liver resection at the Rotterdam University Hospital, 1984/1999].
AB  - OBJECTIVE: To evaluate the results of partial liver resection in patients with
      liver metastases. DESIGN: Retrospective. METHOD: All of the patients who
      underwent a partial liver resection at the Rotterdam University Hospital during
      the period June 1984-August 1999 due to one or more metastases of a colorectal
      carcinoma were traced in the computerised hospital archive. Data concerning the
      primary tumour, the diagnostics carried out, the liver resection carried out and
      the clinical outcome after the operation were analysed using the statistical
      software SPSS. The actuarial survival was determined according to the Kaplan
      Meier method. RESULTS: In total 163 patients underwent an operation: 108 men and
      55 women, with a mean age of 58 years (range: 32-77). Postoperative morbidity
      occurred in 34 patients (21%), mostly infections and gall leakage. During the
      hospital admission 10 patients died (6%). In the follow-up period, mean 30.2
      months (median: 23.8) there was a recurrence of colorectal carcinoma in 82 of the
      patients (50%). The actuarial 5-year survival chance was 37%. The only
      statistically significant unfavourable prognosis factor for survival, was a
      larger tumour volume in the liver at the time of the hepatectomy.

PMID- 11851084
TI  - [Severe hypokalemia with paralysis in a patient with distal renal tubular
      acidosis as an initial expression of Sjogren's syndrome].
AB  - In a 33-year-old woman with a recent flaccid paralysis of the arms and legs,
      laboratory tests demonstrated a severe hypokalemia with hyperchloremic metabolic
      acidosis and abnormally acidified urine. The urinary anion gap was positive in
      the presence of acidosis, thus establishing the diagnosis of distal renal tubular
      acidosis. The patient made a full recovery after potassium and alkali
      replacement. Further investigation revealed Sjogren's syndrome as the underlying
      cause.

PMID- 11851085
TI  - [A 35-year-old man with gynaecomastia as the first symptom of hyperthyroidism].
AB  - A 35-year-old man suffered painful bilateral gynaecomastia for 2 months due to
      serious Graves' hyperthyroidism. During treatment with propylthiouracil and
      levothyroxine, the plasma concentrations of thyroid hormone, sex hormones and sex
      hormone-binding globulin normalised and the gynaecomastia disappeared.
      Gynaecomastia occurs in 30 to 40% of men diagnosed with Graves' hyperthyroidism.
      However, gynaecomastia as a presenting symptom of this autoimmune disease is
      uncommon.

PMID- 11851086
TI  - [Tuberculosis control in Eastern Europe].
AB  - The annual incidence of tuberculosis in Eastern Europe has increased from an
      average of 40 per 100,000 in 1990 to 60 per 100,000 in 1998. In particular, the
      increase in multi-drug resistant tuberculosis, which is difficult to treat, is a
      great cause for concern due to increasing migration. The breakdown in the
      healthcare infrastructure, which has jeopardised medicine supplies, is largely to
      blame for this increased incidence. Eastern Europe has a long standing
      tuberculosis control system which is characterised by extensive and specialised
      knowledge about the disease, but also by a lack of knowledge concerning its
      control. A great deal of attention is paid to the number of medical procedures
      carried out, but the results are ignored. For a few years now, Western aid
      organisations have been involved in tuberculosis control in Eastern Europe and
      have introduced the WHO DOTS strategy ('directly observed treatment, short
      course'), with emphasis on case detection by sputum smear microscopy, directly
      observed uninterrupted treatment with short-course intensive chemotherapy and
      evaluation of treatment outcome. The Netherlands play a prominent role in these
      activities. The DOTS strategy is only slowly becoming accepted in Eastern Europe,
      particularly in Russia. It is in Western Europe's interest to help Eastern Europe
      rebuild their tuberculosis control system. Education and training are important
      elements to prepare doctors for their new role, in which public health should be
      given greater emphasis.

PMID- 11851087
TI  - [A family with malaria: from asymptomatic to life-threatening].

PMID- 11851088
TI  - [Low 5-year remission percentage after surgical treatment of 126 basal cell
      carcinomas with frozen section diagnosis].

PMID- 11851089
TI  - [The short preoperative health status assessment as proposed by the Health
      Committee cannot be used in practice].

PMID- 11851090
TI  - BRFSS and beyond: methodological quality of the measures from the Behavioral Risk
      Factor Surveillance System.

PMID- 11851091
TI  - Reliability and validity of measures from the Behavioral Risk Factor Surveillance
      System (BRFSS).
AB  - OBJECTIVES: To assess the reliability and validity of measures on the BRFSS, to
      assist users in evaluating the quality of BRFSS data, and to identify areas for
      further research. METHODS: Review and summary of reliability and validity studies
      of measures on the BRFSS and studies of measures that were the same or similar to
      those on the BRFSS from other surveys. RESULTS: Measures determined to be of high
      reliability and high validity were current smoker, blood pressure screening,
      height, weight, and BMI, and several demographic characteristics. Measures of
      both moderate reliability and validity included when last mammography was
      received, clinical breast exam, sedentary lifestyle, intense leisure-time
      physical activity, and fruit and vegetable consumption. Few measures were of low
      validity and only one measure was determined to be of low reliability. Several
      other measures were of high or moderate reliability or validity, but not both.
      The reliability or validity could not be determined for some measures, primarily
      due to lack of research. CONCLUSIONS: Most questions on the core BRFSS instrument
      were at least moderately reliable and valid, and many were highly reliable and
      valid. Additional research is needed for some measures.

PMID- 11851092
TI  - [Development of a culturally sensitive psychiatric screening instrument for
      detecting emotional problems among Ethiopian immigrants in Israel].
AB  - BACKGROUND: Studies have demonstrated that a large percentage of patients in
      primary care clinics suffer from emotional problems. Many of the patients who
      suffer from these problems are not diagnosed properly, and do not receive
      appropriate treatment by the medical staff. The problem is especially severe for
      patients who immigrated to Israel from Ethiopia. This is mainly due to the
      difference between the medical belief system familiar to the Ethiopian immigrants
      and that of the non-Ethiopian doctors. It is also the result of the use of
      culturally typical idioms of distress by the Ethiopians that are not clearly
      understood by the doctors. The WHO developed the SRQ--Self-Reporting
      Questionnaire, a psychiatric screening instrument to assess populations in
      developing countries. Although this instrument has been widely used both in
      developing and developed countries, it has been found to be problematic in
      certain cultures. The difficulties stem partly from differences between the
      spontaneous idioms of distress used by the interviewees, for example the
      Ethiopians, and the idioms of distress that appear in the SRQ. OBJECTIVE: The
      goal of this research was to develop a psychiatric screening instrument, based on
      the SRQ, which would be valid and culturally sensitive to Ethiopian immigrants in
      Israel. METHODS: The sample included 161 immigrants from Ethiopia, aged 18-55
      years, who were born in the Gondar region. The interviewees were divided into
      three groups according to their "level of treatment": healthy individuals from
      the general population, who were sampled, mainly using the "quota sampling"
      method, in those cities where a high percentage of Ethiopian immigrants reside;
      consecutive patients in primary care clinics and in specialist clinics in the
      same cities; and consecutive patients in care in psychiatric clinics throughout
      the country. The research instruments included an expanded version of the SRQ
      (the SRQ-E) and the expanded version of the BPRS--Brief Psychiatric Rating Scale.
      The validity of each question of the SRQ-E was examined in order to create a new
      psychiatric screening questionnaire that is both valid and parsimonious. The
      internal consistency and the construct and criterion validity of this new
      screening questionnaire were then examined. The sensitivity and specificity of
      the instrument for detecting psychopathology were assessed. RESULTS: The new
      screening instrument was determined to be valid: a score of 7 distinguishes
      between those with and without psychopathology, with a sensitivity and a
      specificity of 87%.

PMID- 11851093
TI  - [The application of the patients' rights law in psychiatry].
AB  - The application of the Israeli law of patients rights in psychiatry raises
      several dilemmas. These dilemmas include the competence of a psychotic patient to
      consent to psychiatric hospitalization and the difficulties of sharing
      information concerning the psychiatric patient with the family although they are
      essential partners in the rehabilitation process. Another major problem is the
      loss of confidentiality of minor patients by the parents (or guardians) rights to
      examine their medical documentation. These issues have detrimental implications
      on the diagnosis and therapeutic process.

PMID- 11851094
TI  - [Survivin: anti-apoptosis protein and a prognostic marker for tumor progression
      and recurrence].
AB  - The recently discovered 16.5 kDa protein survivin was found to inhibit the two
      early apoptotic enzymes caspase-3 and caspase-7, thus preventing programmed cell
      death. Survivin may act simultaneously with the bel-2 family proteins, but has a
      different apoptosis inhibitory mechanism. Numerous reports have demonstrated the
      expression of survivin in various tumors such as neuroblastoma, melanoma, bladder
      carcinoma, breast and lung non-small cell tumors, esophegeal and colo-rectal
      carcinomas and leukemic cells. In contrast, this protein was not traced in
      adjacent normal tissues by either immunohistochemical staining or by PCR analysis
      of the expression of survivin mRNA. Importantly, there seems to be a positive
      correlation between survivin expression and tumor grading, as well as an
      indication of tumor recurrence after resection or chemotherapy. Potentially, this
      protein could add to the repertory of diagnostic and prognostic markers in
      monitoring oncologic patients.

PMID- 11851096
TI  - [The European Federation of Internal Medicine in Edinburgh 9-12 May, 2001].

PMID- 11851095
TI  - [The family of metalloproteinases and their immunomodulatory significance].

PMID- 11851097
TI  - [The second international symposium on the treatment of children with cerebral
      palsy or brain injuries with high-pressure oxygen].

PMID- 11851098
TI  - [Some words that get on the nerves].

PMID- 11851099
TI  - [The Rambam and his opposition to vegetables as nutrients].

PMID- 11851101
TI  - [Kashin-Beck disease in Israel?].
AB  - This is a case report of a 21 year old young man who suffers from severe early
      bilateral hip joint osteoarthrosis. Due to this surprising finding we discuss the
      differential diagnosis between Kashin-Beck disease, an endemic disease of the
      patients prior living area (east Siberia) and severe hip joint damage secondary
      to juvenile rheumatoid arthritis and other diseases.

PMID- 11851100
TI  - [Mentally ill soldiers in the reserves--professional secrecy and therapist
      judgment regarding reporting incapacity to carry weapons].
AB  - Medical confidentiality is a complex subject, requiring contemplation by both
      therapists and patients. Medical confidentiality is conventionally regarded to be
      in the best interest of the individual and opposed to public demands for
      information, especially on issues in which danger is involved. The therapist
      represents both the patient and the public, belonging to both worlds and acting
      according to existing laws and regulations. We report six incidences, in which
      important medical information was transferred to the army by the patient himself,
      rather than by the therapist. The therapist must consider his own judgment on the
      subject, in conjunction with existing laws and regulations.

PMID- 11851102
TI  - [The evaluation of mental capability to use firearms: practical and ethical
      questions].
AB  - This paper presents the results of a survey of 116 men who underwent psychiatric
      evaluation of their capacity to carry firearms. The data was collected using a
      standardized form. The results show the following profile: male, married with
      children, high school education and requesting the license to carry firearms due
      to reasons related to their type of work or their place of residence. The results
      point to several conclusions regarding the way in which these evaluations are
      performed. RECOMMENDATION: To centralize the process of evaluating the types of
      dangers within the auspices of one single medical institution.

PMID- 11851103
TI  - [Neurologic complications following liver transplantation].
AB  - Neurologic complications are very common following liver transplantation and
      appear in 30%-90% of the patients. These complications represent a wide array of
      etiologies, often presenting complicated diagnostic options. The primary liver
      disease for which the patient underwent the transplantation can cause neurologic
      complications, or they can be a presentation of a metabolic or vascular
      derangement. The medications given to liver transplanted patients can cause
      neurologic complication either directly via drug side effects or indirectly via
      immune-suppression and secondary opportunistic infections of the nervous system.
      We present two cases of liver transplanted patients, one suffering from a complex
      neurologic syndrome attributed to her primary Wilsons disease and the second with
      recurrent encephalopathy following transplantation attributed to a porto-systemic
      shunt. We review the current literature on the subject.

PMID- 11851104
TI  - [A treatment unit within a medical center for adult survivors of childhood sexual
      abuse: an interdisciplinary approach].
AB  - Childhood sexual abuse is A highly prevalent phenomenon that has disastrous
      lifelong effects on emotional and physical development, interfering with almost
      every aspect of a persons existence. Research and clinical observations of
      psychological trauma have led to a clinical recognition of the complexity of
      survivors clinical presentation and needs, helping therapists to develop special
      treatment models for them. In this article we present a treatment model for
      survivors of childhood sexual abuse that was designed and implemented over the
      past three years in a specialized unit of psychiatric services at the Tel-Aviv
      Medical Center. Three case studies are used to illustrate the treatment process
      and the guiding theoretical model. The existence of such a treatment unit within
      a general medical center makes it possible to provide a diverse population of
      survivors with integrated psychological and physical care geared to their various
      needs. The former focuses on mental stabilization, strengthening of the ego, and
      improved adjustment to the trauma and its effects. Interdisciplinary guidance by
      the therapist ensures appropriate medical attention to the wide range of problems
      typical of survivors, such as gynecological and gastroenterological problems,
      eating disorders, and sexual differences.

PMID- 11851105
TI  - [Somatization disorder in children and adolescents].
AB  - Somatization disorder in children and adolescents is a common anxiety disorder.
      Errors and delays in diagnosis may incur unnecessary expensive and sometimes
      dangerous medical workup. We review the epidemiology, clinical features,
      treatment approaches and prognosis. One case study is presented in order to
      demonstrate this problematic disorder.

PMID- 11851106
TI  - [The history of the Israeli Medical Association].

PMID- 11851107
TI  - [Consumption of soy and phytoestrogens--is there a place for dietary
      guidelines?].
AB  - Phytoestrogens (PE), and soy protein consumption are suggested to be associated
      with reduced risk of developing breast and prostate cancer, slowing the
      progression of renal failure, improved bone density, reduced serum lipid levels,
      and reduction in the risk of developing coronary artery disease. In infants,
      breast milk is the feeding of choice in the first months of life, and soy-based
      formulas should only be given to infants with intolerance of cows milk protein.
      In adults, except for reduced serum lipid levels, there is a lack of scientific
      evidence for health claims related to high phytoestrogen consumption.

PMID- 11851108
TI  - [Influences of environment and knowledge on celiac disease--new perspectives].

PMID- 11851109
TI  - [New aspects of celiac disease].
AB  - Celiac disease (CD) is an inflammatory condition of the upper small intestine
      which is caused by gluten ingestion in genetically susceptible patients. Over the
      past few years, significant changes have occurred in our understanding of CD in
      terms of patterns of disease expression, pathological manifestations, associated
      diseases, definition of high-risk patients, screening policy and diagnosis, and
      epidemiological, genetic, immunological and pathogenetic aspects. We review new
      perspectives of CD in order to enhance the familiarity of physicians with a
      disease that is now considered to be more common than was thought in the past.

PMID- 11851110
TI  - [The management of HIV patients during surgery and in the delivery ward:
      anesthetic considerations].
AB  - To date a total of more than 50 million individuals worldwide have been infected
      with HIV and more than 20 million have died from the disease. Two thirds of the
      known carriers of HIV 36 million worldwide, live in Africa. In Israel, as of
      December 31, 2000, there are a total of 2,843 reported carriers and 165 persons
      alive with AIDS. On the basis of future projections of increasing incidence of
      HIV/AIDS in obstetric patients undergoing anesthesia and surgery, obstetricians
      and anesthesiologists should be aware of the disease and its impact on anesthetic
      techniques and possible interactions between anesthetic drugs and HIV therapeutic
      agents. Surgical staff members should be knowledgeable and updated concerning
      safety precautions during surgical and anesthetic procedures.

PMID- 11851111
TI  - [Soy and phytoestrogens consumption and health policy hesitation or certitude].
AB  - Soy and phytoestrogens are controversial as to their beneficial effects on health
      and the prevention of disease. To date, dietary recommendations in Israel do not
      specify a diet rich in soy and phytoestrogens. In order to establish a policy on
      this issue, we carried out a comprehensive, updated review of the relevant
      scientific literature. Data on the role of these substances in the primary and
      secondary prevention of cancer are limited. As yet, there is no conclusive
      evidence on the efficacy of phytoestrogens and soy in the prevention of
      osteoporosis. Their effect on fertility in animals and humans is still unclear.
      There are no data on the long-term risks or benefits of using soy-based formulae
      in infancy. Therefore, for those who cannot be breast-fed, cow-milk based
      formulae are recommended. Currently, the most supportive evidence for health
      benefits of soy can be found in studies on the prevention of cardiovascular
      diseases.

PMID- 11851112
TI  - [The medical treatment of upper gastrointestinal bleeding in the new millennium].
AB  - Treatment is advocated for patients manifesting upper gastrointestinal bleeding.
      The medical arsenal consists of H2-receptor blockers and proton pump inhibitors.
      Studies which were performed to test the efficacy of H2-blockers for bleeding did
      not present consistent conclusions. In vitro studies proved that H2-blockers
      given parenterally lose their efficacy after 24 hours, and the pH-drops back to
      near pretreatment level (pH 2.7). Omeprazole, the oldest pump inhibitor on the
      market, when given parenterally affects pH-within 30 minutes and does not lose
      its efficacy in the forthcoming days. In a few studies, when given
      enterally/parenterally Omeprazole lowered rates of recurrent bleeding, surgery
      and the number and rate of blood units transfused. On the whole it seems that H2
      blockers have little or no role in the treatment of patients with upper
      gastrointestinal bleeding, while a proton pump inhibitor is of probable
      therapeutic value. There is no definite answer as to whether the drug should be
      given enterally or parenterally. It seems logical to start treatment of high-risk
      patients parenterally and the rest of the patients enterally (orally or via a
      nasogastric tube).

PMID- 11851113
TI  - [Treatment of cutaneous leishmaniasis--an update].
AB  - Cutaneous leishmaniasis (CL) is a skin disease that manifests as ulcerated
      nodules, up to several centimeters in size, that persist for many months in spite
      of various therapies. The disease is a dermal infection with eukaryotic protozoa
      of the genus Leishmania, transferred by the bite of a female sand-fly, and
      therefore usually present on exposed areas of the skin such as limbs and face.
      The disease is endemic in specific geographical areas of Israel, mainly in the
      Jordan and Jericho valley, part of the Dead-Sea area, Kfar Edomim area, and parts
      of the Negev such as Ketziot and the Arava. Cutaneous leishmaniasis (CL) presents
      a significant health hazard in Israel, mainly to non-residents, such as soldiers
      or new immigrants, travelling to endemic areas. It is also not unusual to find
      patients with CL acquired during adventure travelling to South America. Treatment
      modalities available for treating CL are limited and often unpleasant. Over the
      past few years several new therapies for visceral leishmaniasis have become
      available raising hope for the development of more effective treatment options
      for CL. In this review we discuss the disease and its therapeutic options and
      also report a novel treatment for CL using ethanolic amphotericin B.

PMID- 11851114
TI  - [Cognitive assessment in geriatric rehabilitation].
AB  - Geriatric rehabilitation is a prolonged and expensive process. There is a need to
      evaluate the rehabilitation potential because of the increasing number of elderly
      in the population and limited resources. Cognition is one of the components of
      occupational performance and its evaluation is a crucial part of comprehensive
      geriatric assessment. Cognitive evaluation is one of the predictors of function
      among elderly in the community and also assists in predicting their
      rehabilitation potential during hospitalization. High prevalence of cognitive
      decline with aging and the difficulties in its early assessment during
      hospitalization emphasizes the utmost importance of this evaluation in predicting
      the functional prognosis of the patient. This article reviews the main common
      tools for cognitive evaluation, which are in use clinically, and also used in
      research, for geriatric rehabilitation in Israel. These were compared with the
      principles of dynamic cognitive assessment. We aim to assess the need to add
      dynamic diagnostic tools to supplement those in common use. This will assist in
      providing an optimal mechanism for cognitive evaluation during geriatric
      rehabilitation.

PMID- 11851115
TI  - [Extensive subcutaneous hemorrhage complicating primary amyloidosis].
AB  - Bleeding manifestations are common in patients with primary as well as secondary
      amyloidosis and have been attributed to different mechanical and metabolic
      causes. Factor X deficiency has been described in patients with primary
      amyloidosis, although severe bleeding is not common in these patients. We
      describe a patient with extensive subcutaneous hematoma, a sign that served as
      the major indicator assisting us in establishing the diagnosis of primary
      amyloidosis.

PMID- 11851116
TI  - [Primary herpetic gingivostomatitis--clinical aspects and anti-viral treatment].
AB  - Herpetic gingivostomatitis is the most common specific, clinical manifestation of
      primary herpes simplex type I infection. It is prevalent in the 1-3-year age
      group. The disease involves the buccal and gingival mucosa, and tongue and lasts
      approximately 2 weeks. Two recent open studies reported a more rapid regression
      of symptoms after treatment with acyclovir suspension. Three randomized double
      blind placebo-control trials have clearly demonstrated that early acyclovir
      treatment significantly shortens the duration of all clinical manifestations and
      infectivity of affected children compared to placebo. RECOMMENDATION: In
      conclusion, we recommend acyclovir for the treatment of herpetic
      gingivostomatitis. Treatment should begin within the first three days of disease
      onset. The proposed therapeutic dose is 15 mg/kg, 5 times daily for 5 days.

PMID- 11851117
TI  - [Dynamic cardiomyoplasty].
AB  - The high prevalence of end-stage heart failure and its influence on the quality
      of life, force the medical community to seek effective therapeutic modalities.
      Heart transplantation is the accepted therapy for such patients, nevertheless, a
      significant percentage of patients do not reach transplantation due to the
      shortage of donors. Therefore, the establishment of surgical alternatives is very
      important. Dynamic cardiomyoplasty is accepted as an alternative to heart
      transplantation. In this technique skeletal muscle is wrapped around the heart
      and stimulated synchronously with the heart itself. We describe the present
      status of this procedure.

PMID- 11851118
TI  - [Sports injuries among children].
AB  - In addition to the very positive effect of physical activity on health, sport is
      liable to cause injury and disability. In Israel, physical activity has become
      part of leisure time activity over the years. This combination has led to a
      consequential rise in the risk of injury. Most sport injuries are mild and do not
      require hospital treatment, but they may be severe and sometimes lead to
      hospitalization, permanent disability and even death. In 1995-6, there were 356
      sports related injuries among children 5-17 years old, which were registered in
      the Israeli National Trauma Registry (INTR). These represented 8.8% of all
      injuries registered in the INTR for children of that age in 1995-6. In order to
      promote the prevention of sports related injuries, the magnitude of the problem
      must first be identified and the incidence and severity of the sports injuries
      described. In Israel there is no systematic surveillance of sports injuries, nor
      knowledge of the specific patterns of injury in Israel. In order to reduce the
      incidence and severity of sports injuries in Israel, there is a necessity to
      improve the level of information regarding such injuries through the
      establishment of a national sports injury surveillance system.

PMID- 11851119
TI  - [Chickenpox during pregnancy].
AB  - Chickenpox during pregnancy is very uncommon and is known to cause fatal
      malformation during the first half of pregnancy. The infection during pregnancy
      is also associated with maternal morbidity and mortality. Furthermore, there may
      also be neonatal complications. Thus, any pregnant woman with Varicella infection
      should be hospitalized and followed-up closely. In this review, we examined the
      literature on Varicella Zoster during pregnancy with regard to prevalence,
      prenatal diagnosis, management and prevention.

PMID- 11851120
TI  - Antiretroviral news from the 41st ICAAC.

PMID- 11851121
TI  - IDSA update: sexually transmitted diseases and HIV.

PMID- 11851122
TI  - Report from ICAAC: update on opportunistic infections.

PMID- 11851123
TI  - Update from the 3rd International Workshop on Adverse Drug Reactions and
      Lipodystrophy in HIV.

PMID- 11851124
TI  - HIV notes from the 39th Annual Meeting of the IDSA.

PMID- 11851126
TI  - Surgeon general leaves this month as several key posts remain unfilled.

PMID- 11851125
TI  - AIDS advocates see Toyota ruling as narrowing of disability rights.

PMID- 11851127
TI  - Effective treatment options to be examined in 9-year study.

PMID- 11851128
TI  - Medicaid. Tennessee receives extension for managed-care program.

PMID- 11851129
TI  - Prevention. Conference to examine drug use, sexual behavior risks.

PMID- 11851130
TI  - Bioterrorism topped public's list of 2001 health concerns.

PMID- 11851131
TI  - Bush signs bills to fund domestic, global AIDS programs.

PMID- 11851132
TI  - Medical marijuana. Advocates file suit to seek new vote in District of Columbia.

PMID- 11851133
TI  - Students protest use of cats in HIV research; lawsuit filed.

PMID- 11851134
TI  - Custody. Mother who left HIV-positive child loses parental rights.

PMID- 11851135
TI  - San Francisco has right to criticize religious ad campaign.

PMID- 11851136
TI  - Discrimination. Couple receives $100,000 in challenge to foster-care rules.

PMID- 11851137
TI  - Spitting threat brings habitual-offender status, 25-year term.

PMID- 11851138
TI  - Hungry for knowledge.

PMID- 11851139
TI  - Taking charge of my health.

PMID- 11851140
TI  - I'm still here!

PMID- 11851141
TI  - Marriage is not a vaccine against AIDS.

PMID- 11851142
TI  - So let's talk!

PMID- 11851143
TI  - Enjoying this period of grace.

PMID- 11851145
TI  - Coming out: a mother's story.

PMID- 11851146
TI  - This little girl.

PMID- 11851144
TI  - I will urge caution.

PMID- 11851147
TI  - The making of an AIDS activist.

PMID- 11851148
TI  - A wonderful life.

PMID- 11851149
TI  - Stent-or-bypass dilemma revisited.

PMID- 11851150
TI  - I'm concerned that my young son might become allergic to our cat, but recently I
      heard that the cat might actually protect him from developing allergies. Should
      we keep the cat or not?

PMID- 11851151
TI  - What's the recommended duration for a nap? Is there an ideal time of day?

PMID- 11851152
TI  - Overcoming social anxiety disorder.

PMID- 11851153
TI  - Herceptin: help for advanced breast cancer.

PMID- 11851155
TI  - Where Lyme disease lives.

PMID- 11851154
TI  - Internet hosts rumors and hoaxes galore.

PMID- 11851156
TI  - Working out may ward off Alzheimer's.

PMID- 11851157
TI  - Let them eat cake?

PMID- 11851158
TI  - Exercising away depression.

PMID- 11851159
TI  - "Hear this" about ear infections.

PMID- 11851160
TI  - Arsenic alert.

PMID- 11851161
TI  - Fresh fish folly.

PMID- 11851162
TI  - Exercise: how much is enough?

PMID- 11851163
TI  - Does HRT promote ovarian cancer?

PMID- 11851164
TI  - Osteoporosis: the hormone connection.

PMID- 11851165
TI  - I have a family history of prostate cancer. Can what I eat affect my chances of
      getting this disease?

PMID- 11851166
TI  - What is restless legs syndrome?

PMID- 11851167
TI  - You can prevent type 2 diabetes.

PMID- 11851168
TI  - AEDs for all?

PMID- 11851169
TI  - What is autoimmunity?

PMID- 11851170
TI  - Alcohol update.

PMID- 11851171
TI  - Strong support for regular mammograms.

PMID- 11851172
TI  - Boric acid for yeast infections.

PMID- 11851173
TI  - Reducing stress can drive down blood pressure.

PMID- 11851174
TI  - Breast cancer risk by age for women.

PMID- 11851175
TI  - Babies, bacteria, and allergies.

PMID- 11851176
TI  - Behavior therapy for insomnia.

PMID- 11851177
TI  - [Low back pain].

PMID- 11851178
TI  - [Diagnosis of infectious diseases. Brain abscess].

PMID- 11851179
TI  - [Why is QT interval interesting?].
AB  - A prolonged Q-T interval is generally associated with increased risk of
      ventricular arrhythmias, like torsade de pointes, and death. It has recently
      become apparent that not only antiarrhythmic drugs such as sotalol and Kinidin,
      but also a variety of nonantiarrhythmic drugs, like certain antihistamines,
      antimicrobial drugs, psychiatric drugs, and cisapride, may induce prolongation of
      the Q-T interval and torsade de pointes. Special concern should be drawn to the
      co-administration of drugs that interfere with the metabolism and elimination of
      these drugs, such as ketoconazole. Patients with congenital long Q-T syndrome,
      patients with heart disease, with hypokalaemia or hypomagnesaemia, and women have
      an increased risk. Every sign on dizziness or syncope should be regarded as a
      warning sign of possible arrhythmia in patients treated with drugs that
      potentially prolong the Q-T interval. Measurement of the Q-T interval before and
      during treatment is generally recommended in high-risk patients.

PMID- 11851180
TI  - [Low back pain in children and adolescents. Prevalence, risk factors and
      prevention].
AB  - The occurrence of non-specific low back pain (LBP) in 14-16-year-old adolescents
      has almost reached the level in adults. Among other things, the ranges of
      reported prevalences are wide, owing to the use of various outcome measures,
      questionnaire terminology, and differences in age and gender. A review of the
      literature points out some important possible risk factors for LBP: minimal
      physical activity, intensive sports, genetics, psychosocial factors, smoking and
      leisure-time activities with a high physical impact. However, the causal
      relations are not clear, and the morbidity related to non-specific LBP in
      adolescents has not yet been elucidated. Few intervention studies have been
      published, and the means of prevention have not yet been found. Research in LBP
      in adolescents deserves a high priority in the future to provide evidence for a
      relevant prevention strategy.

PMID- 11851181
TI  - [Does sitting at work cause low back pain?].
AB  - INTRODUCTION: Low back pain (LBP) is a common condition that, according to
      standard textbooks and several review articles, is associated with sitting-while
      at-work. However, to our knowledge, no meta-analysis or critical systematic
      literature reviews have been published. MATERIALS AND METHODS: The Medline,
      Embase, and OSH-ROM databases were searched for articles dealing with sitting at
      work in relation to low back pain for the years 1985-1997. Original studies were
      divided into those dealing with sitting-while-working and those dealing with
      sedentary occupations. Each article was systematically abstracted for core items.
      The quality of each article was determined on the representativeness of the study
      sample, response rate, the definition of LBP, and the statistical analysis.
      RESULTS: Thirty-five reports were identified: 14 dealing with sitting-while
      working and 21 with sedentary occupations. Eight studies were found to fulfill
      the above-mentioned criteria. Regardless of quality, all but one of the studies
      failed to find a positive association between sitting-while-working and LBP. High
      quality studies showed a marginally negative association for sitting compared to
      diverse workplace exposures, for instance standing, driving, lifting, bending,
      and compared to diverse occupations. One low quality study associated sitting in
      a poor posture with LBP. DISCUSSION: Out of 35 studies, only eight fulfilled the
      very basic quality criteria. Nevertheless, both high-quality and low-quality
      studies are consistently in agreement about the lack of positive association, and
      we conclude that the extensive recent epidemiological literature does not support
      the popular opinion that sitting-while-at-work is associated with LBP.

PMID- 11851182
TI  - [Treatment of Frey syndrome with intracutaneous injections of botulinum toxin].
AB  - In a prospective study, we have examined the efficacy of intracutaneous
      injections of botulinum toxin in Frey's syndrome. In a controlled study, the long
      term results after surgical treatment for parotid tumors were investigated in 98
      consecutive patients. Patients, who reacted positive by Minor's iodine-starch
      test, and who had subjective complaints too, were offered treatment. A total of
      four patients entered the study. The affected area was visualised by Minor's
      iodine-starch test. The coloured areas were injected with botulinum toxin (Botox)
      2.5 U/0.1 ml. We injected 0.5 U/cm2. The distance between each injections points
      was 1 cm. All patients became free of symptoms. The injections were given with
      little discomfort to the patients and no side effects. At the control one year
      after the injections three patients had minor recurrent complaints, which were
      treated successfully by reinjections. Botulinum toxin injections are thus safe
      and effective in the treatment of FS.

PMID- 11851183
TI  - [Yield of a coronary arteriography database. A study of 5.536 registrations at
      the cardiologic laboratory, Rigshospitalet].
AB  - INTRODUCTION: Coronary arteriography (CAG) is an expensive investigation that
      provides potentially valuable information, but also carries a risk of severe
      complications. It is therefore natural to examine the usefulness of an existing
      database on CAG. METHODS: The analysis covers all registrations of CAG entered
      into the database at the Heart Centre at Rigshospitalet, Copenhagen, from April
      1999 to September 2000. RESULTS: Altogether, 5536 CAGs were registered. The
      indication was stable coronary artery disease in 52.0% and acute ischaemic heart
      disease in 25.5%. As an example of the medical information available from the
      data base, it is notable that left main coronary stenosis or three-vessel
      disease, conditions in which coronary bypass surgery increases long-term
      survival, was found in 42.4% of patients with angina pectoris in Canadian
      Cardiovascular Society (CCS) class 4, but also in 24.4% of patients in CCS class
      1. DISCUSSION: Clinical databases, such as the one presented, can ensure that all
      relevant information is stored, and in this case even results in enhanced
      effectiveness, because data may be directly transformed into other formats, such
      as charts. The database furthermore provides clinical information, for instance
      that the severity of angina pectoris cannot identify the most ill patients in
      whom a CABG is potentially life-prolonging. In addition, the database provides
      administrative data that is used in the training of doctors, evaluation of
      referral patterns, surveillance of complications, and in the daily administration
      and planning.

PMID- 11851184
TI  - [Prevention of ischemic heart disease. Testing of three different methods for
      prediction of the risk of developing ischemic heart disease].
AB  - INTRODUCTION: The purpose of this evaluation was to compare estimation of risk of
      IHD, according to PRECARD and guidelines from DSAM and DCS. MATERIAL AND METHOD:
      The evaluation was performed in a general practice setting with relatively few
      elderly patients. Fifty consecutive patients were evaluated, 29 men and 21 women.
      Thirty-four patients were evaluated according to the physician's assessment and
      16 according to the wishes of the patients. RESULTS: Four persons with definite
      ischaemic heart disease were included. According to DSAM, a further eight persons
      were found to have a > 20% risk of developing IHD. According to DCS, ten persons
      and to PRECARD three persons had a > 20% risk. DISCUSSION: Evaluation with
      PRECARD gives a more precise estimation than do DSAM and DCS. PRECARD uses the
      same risk factors as DSAM and DCS, but the HDL level and height/weight are also
      included. In addition, PRECARD estimates the risk of AMI, stroke, and fatal
      events, as well as the most important risk factors. PRECARD is recommended for
      use in general practice.

PMID- 11851185
TI  - [Bilateral blindness in temporal arteritis].
AB  - Two patients with mono-symptomatic unilateral loss of vision are presented. Both
      developed a bilateral loss of vision over a period of 2-3 weeks. No clinical
      suspicion of TA was raised on the basis of symptoms or signs, but a careful
      history and repeated blood tests might have given the correct diagnosis.

PMID- 11851186
TI  - [Urogenital tuberculosis in Danes].
AB  - Extrapulmonary tuberculosis is rare in natives of Denmark, who are not exposed to
      risk factors, such as homelessness and drug or alcohol abuse. Two patients
      diagnosed with advanced urogenital tuberculosis are reported.

PMID- 11851187
TI  - [EGF receptor blockade--a new cancer therapy].

PMID- 11851188
TI  - [Regeneration of the human heart: a fact!].

PMID- 11851189
TI  - [Suspected von Willebrand disease--how to proceed?].

PMID- 11851190
TI  - [Smoking, counseling, questionnaires and science].

PMID- 11851191
TI  - [Diagnosis and treatment of uncomplicated bladder inflammation].

PMID- 11851192
TI  - [Vascular surgeons want--so do cardiologists].

PMID- 11851193
TI  - WHO Expert Committee on Drug Dependence. Thirty-second report.
AB  - This report presents the recommendations of a WHO Expert Committee responsible
      for reviewing information on dependence-producing drugs to assess the need for
      their international control. The first part of the report contains a general
      discussion of the new guidelines for the review of dependence-producing
      psychoactive substances and their implications for the scheduling of ephedrine
      and of the guidelines that were drafted to clarify the scope of control of
      stereoisomers. A summary follows of the Committee's evaluations of six substances
      (4-bromo-2,5-dimethoxyphenethylamine (2C-B), 4-methylthioamphetamine (4-MTA),
      gamma-hydroxybutyric acid (GHB), N-methyl-1-(3,4-methylenedioxyphenyl)-2
      butanamine (MDBD), diazepam and zolpidem), four of which (2C-B, 4-MTA, GHB and
      zolpidem) were recommended for international control. The report also discusses
      the substances that were pre-reviewed by the Committee, five of which
      (amfepramone, amineptine, buprenorphine, dronabinol and tramadol) were
      recommended for critical review at a future meeting.

PMID- 11851194
TI  - Mecamylamine, a nicotinic receptor channel antagonist, affects amylase secretion
      by isolated pancreatic acinar cells.
AB  - It is well established that CCK is a potent stimulator of amylase secretion from
      the pancreatic acinar cells, while nicotine is an effective inhibitor of such
      secretion. The present study was conducted to determine whether mecamylamine, a
      well-established ganglionic blocker drug, could influence amylase secretion from
      the pancreas. Male Sprague-Dawley rats were fasted, sacrificed, the pancreas
      removed, and pancreatic acinar cells isolated and purified. The cells were
      equally divided into 4 different flasks and treated with the following solutions:
      (control), 10 mM nicotine, 10 microM mecamylamine or 100 microM mecamylamine. The
      cells were washed twice after 30 min incubation at 37 degrees C, resuspended in
      HR buffer, and amylase release in response to graded doses of CCK-8 was measured
      in cells from each flask. The study was repeated four times. Basal amylase
      release was not different by treatment with nicotine or different doses of
      mecamylamine. In response to CCK-8, amylase release was decreased by nicotine and
      by mecamylamine (100 microM) when compared with control. Amylase release was
      similar between control and mecamylamine (10 microM). Peak amylase released with
      the maximal dose of CCK-8 (1 x 10(-10) M) was less in cells treated with nicotine
      when compared with those measured cells treated with saline or with the two doses
      of mecamylamine. The release of amylase was suppressed in a similar manner in all
      treatment groups in response to supramaximal (3 x 10(-10) to 1 x 10(-9) M) doses
      of CCK-8. Mecamylamine, at the high dose, acts on isolated pancreatic acinar
      cells to decrease amylase release in a manner similar to that found with
      nicotine. Both of these drugs, nicotine and mecamylamine, may act via CCK
      receptors via two different intracellular mechanisms.

PMID- 11851195
TI  - Lethality of standard total parenteral nutrition following major liver resection
      in rats is prevented by high arginine and high branched chain amino acids but not
      by glutamine.
AB  - Standard total parenteral nutrition (TPN), with or without fat, in amounts
      approximating the ad libitum intake of normal rats is highly lethal for rats
      following 70% hepatectomy. Because of significant metabolic changes including
      alterations of branched chain amino acids (BCAA), arginine (ARG), and glutamine
      (GLN) associated with serious injury, sepsis, and liver dysfunction, we
      hypothesized that (1) increasing concentrations of BCAA and ARG in TPN and (2)
      including glutamine in the TPN may diminish the lethality. Male Sprague-Dawley
      rats with 70% hepatectomy and jugular vein catheterization were divided into
      groups. Two sets of experiments were conducted. In Experiment 1, the effects of
      varying concentrations of BCAA and ARG in the TPN infusate, singly and together,
      were assessed: Group 1, Standard TPN (19% BCAA, 4.8 g ARG/L); Group II, High BCAA
      TPN (35% BCAA, 4.8 g ARG/L); Group III, High ARG TPN (19% BCAA, 9.6 g ARG/L);
      Group IV, High ARG, High BCAA TPN (35% BCAA, 9.6 g ARG/L; Group V, chow and tap
      water ad libitum. In experiment 2, the effect of 2% GLN in TPN was evaluated:
      Group A, Standard TPN and Group B, 2% GLN TPN. All infusates were isocaloric (216
      Kcal/Kg/d) and isonitrogenous (1.94 g N/Kg/d) delivered at half concentration on
      postoperative day 1, 3/4 concentration on postoperative day 2, and at full
      concentration thereafter. Experiment 1: Thirty-three to 36% of rats in Groups I
      (Standard TPN) (4/11), II (High BCAA TPN) (4/11) and III (High ARG TPN) (4/12)
      died within 6 days. In sharp contrast, none died in Groups IV (High BCAA, High
      ARG TPN) and V (rat chow and tap water) (P < 0.05 in each comparison). Among rats
      in the 4 TPN groups surviving 7 days, there were no significant differences in
      body weight change (minus 3-4%), spleen or lung weight, extent of liver
      regeneration (61-66%). Serum total protein and albumin were significantly higher
      in Group V (chow-fed) (similar to values in normal rats) than in Groups I-IV, P <
      0.05 in each case. Serum total bilirubin was significantly higher in Group I than
      in normals and in Groups II, III, and V. Serum lactate dehydrogenase levels were
      similar in normals and all 5 groups. Serum aspartate amino transferase level was
      higher in Group I than in normals but not significantly different from those
      groups II-V; the latter were similar to normals. Experiment 2: Thirty percent of
      rats in Groups A (Standard TPN) (3/10) and B (GLN TPN) (3/10) died within 6 days.
      Among rats surviving for 7 days, body weight change (minus 3-5%), liver
      regeneration (67-70%), and liver tests were similar in both groups. TPN modified
      to contain high concentrations of both BCAA and ARG (but not of either alone)
      prevented the high frequency of lethality induced by standard TPN in rats with
      70% hepatectomy. No such salutary effect was shown by modifying the TPN to
      contain 2% GLN. The striking benefit observed when TPN containing high BCAA and
      high ARG was infused may be due to the high BCAA leading toward normalization of
      serum amino acid levels, reducing proteolysis, increasing protein synthesis, and
      accelerating early liver regeneration, combined with the high ARG likely reducing
      serum ammonia and leading to increased host defense, and perhaps, thereby,
      preventing bacterial translocation and bacteremia.

PMID- 11851196
TI  - Describing and predicting frequent users of an emergency department.
AB  - The objective of this study was to examine the pattern of emergency department
      (ED) utilization among a cohort of ED users over a 3-year period and to identify
      factors predicting use. Billing records were used to track one hospital's cohort
      of adult frequent ED users (> or = 3 visits/per year) over a 3-year period.
      Frequent and (< 3 visits/per year) infrequent users were compared by age, gender,
      marital status, insurance status, and hospitalization rates. We compared the
      number of ED visits by patients in the two groups during follow-up years.
      Logistic regression analyses were performed to identify factors predicting ED
      visits by patients in the two groups in the follow-up years. Results from the
      study showed that frequent users were younger (P < 0.01) and more likely to be
      male (P < .01). Patients identified as frequent users in the first year were 52
      to 77% more likely to visit frequently in the following two years. Logistic
      regression analysis showed the pattern of prior ED use was the best predictor of
      future use. Other factors (including age, gender, marital status, insurance
      status, and hospitalization following an ED visit) were not significant
      independent predictors of frequent ED use. Our data revealed that the past
      history of frequent ED use is predictive of future frequent ED use. Studies are
      needed on effective interventions to determine the reasons for continued frequent
      ED use.

PMID- 11851197
TI  - Alcohol, tobacco (nicotine) and pancreatic pathophysiology.
AB  - Current knowledge indicates that chronic use of alcohol is implicated in the
      etiology of chronic pancreatitis and probably in pancreatic cancer and that
      chronic use of tobacco is associated with pancreatic cancer and probably
      pancreatitis. Studies by others, and by us, support this knowledge. In addition,
      our studies suggest that nicotine, which is a major component and an additive
      component of tobacco, is probably a major factor in these pathological effects.
      The possibility exists that nicotine may also play a role in tobacco induced
      diseases of other organs of the body.

PMID- 11851198
TI  - Highlights of the 14th Annual Scientific Meeting of the Association for Academic
      Minority Physicians, 2000.

PMID- 11851199
TI  - Diversity: the need, the challenge, the promise.

PMID- 11851200
TI  - Documentation of smoking: role of age, gender, and ethnicity.
AB  - This study assessed the role of age, gender, and ethnicity in chart documentation
      of smoking by primary care providers. Clinic patients (n = 304) were asked their
      smoking status and medical records were reviewed. Twenty-nine percent of reviewed
      patients were smokers, 27.6% former smokers, and 43.1% nonsmokers. Providers were
      more likely to document smoking among males (OR = 4.6; 95% CI = 2.2-9.5), middle
      aged patients (OR = 4.0; 95% CI = 1.4-11.0), and smokers (OR = 8.1; 95% CI = 4.1
      16.0). Data revealed selective documentation of smoking in males and middle-aged
      patients by providers, suggesting gender and age bias in the recognition and
      documentation of this risky behavior. We conclude that providers should screen
      for smoking in all patients regardless of age or gender.

PMID- 11851201
TI  - Bariatric surgery for severe obesity.
AB  - Severe obesity is associated with multiple comorbidities and is refractory to
      dietary management with or without behavioral or drug therapies. There are a
      number of surgical procedures for the treatment of morbid obesity, including
      purely gastric restrictive, a combination of malabsorption and gastric
      restriction or primary malabsorption. The purely gastric restrictive procedures,
      including vertical banded gastroplasty and laparoscopic adjustable silicone
      gastric banding, do not provide adequate weight loss. African-American patients
      do especially poorly after the banding procedure with the loss of only 11% of
      excess weight in one study. Gastric bypass (GBP) is associated with the loss of
      66% of excess weight at 1 to 2 years after surgery, 60% at 5 years and 50% at 10
      years. For unknown reasons, African-American patients lose significantly less
      weight than Caucasians after GBP. There is a risk of micronutrient deficiencies
      after GBP, including iron deficiency anemia in menstruating women, vitamin B12,
      and calcium deficiencies. Prophylactic supplementation of these nutrients is
      necessary. Recurrent vomiting after bariatric surgery may be associated with a
      severe polyneuropathy and must be aggressively treated with endoscopic dilatation
      before this complication is allowed to develop. The malabsorptive procedures
      include the partial biliopancreatic bypass (BPD) and BPD with duodenal switch
      (BPD/DS). The BPD appears to cause severe protein-calorie malnutrition in
      American patients; the BPD/DS may be associated with less malnutrition. Weight
      loss failure after GBP does not respond to tightening a dilated gastrojejunal
      stoma or reducing the size of the gastric pouch. These patients may require
      conversion to a malabsorptive distal GBP, similar to the BPD. However, because of
      the risk of severe protein-calorie malnutrition and calcium deficiency BPD should
      be reserved for patients with severe obesity comorbidity. The risk of death
      following bariatric surgery is between 1% and 2% in most series but is
      significantly higher in patients with respiratory insufficiency of obesity. In
      most patients, surgically induced weight loss will correct hypertension, type II
      diabetes mellitus, sleep apnea, obesity hypoventilation syndrome,
      gastroesophageal reflux, venous stasis disease, urinary incontinence, female
      sexual hormone dysfunction, pseudotumor cerebri, degenerative joint disease
      pains, as well as improved self-image and employability.

PMID- 11851202
TI  - Metastatic choriocarcinoma presenting as a bleeding duodenal ulcer.
AB  - We report a case of a young man with a rare disease, a choriocarcinoma of the
      gastrointestinal tract presenting as a common entity, a bleeding duodenal ulcer.
      Pathological findings and strongly positive immunostains of tissue specimens for
      beta human chorionic gonadotrophin confirmed the entire tumor to be a
      choriocarcinoma ruling out the possibility of an adenocarcinoma with focal
      components of choriocarcinoma or a beta human chorionic gonadotrophin producing
      adenocarcinoma. The pattern of tumor invasion in this case is more suggestive of
      metastatic than primary involvement of the gastrointestinal tract. The diagnosis
      of primary gastrointestinal choriocarcinoma is difficult because of the need to
      meticulously rule out the occurrence of a primary in other organs, which at times
      regresses spontaneously, a diagnosis made more difficult in this case in which no
      autopsy was performed.

PMID- 11851203
TI  - Late-life depression. How to identify its symptoms and provide effective
      treatment.
AB  - Late-life depression is a common but underrecognized and undertreated mental
      illness that may impose enormous disability on patients and families. Diagnosis
      is often complicated by comorbid medical illness, cognitive impairment, and
      adverse life events. Early intervention with a combination of education,
      psychotherapy, and antidepressant medication is recommended. Choice of specific
      agents requires consideration of symptom profile, tolerability, drug
      interactions, and compliance. Older patients may respond more slowly to treatment
      than younger patients and may more readily experience chronicity and recurrence.

PMID- 11851204
TI  - Surviving suicide. How the deaths of two patients changed my approach to late
      life depression.

PMID- 11851205
TI  - Alzheimer's disease. Accurate and early diagnosis in the primary care setting.
AB  - Alzheimer's disease is the most common dementia type and is characterized by a
      gradual, progressive decline in multiple areas of cognition and function. Early
      diagnosis is key because it can initiate the process of patients and family
      adapting to and managing disease symptoms. Moreover, certain pharmacologic
      interventions can impede symptom progression and significantly improve quality of
      life. A spectrum of basic tests and instruments make clinical diagnosis of AD
      attainable in the primary care setting. Treatment with cholinesterase inhibitors
      is targeted toward cognitive enhancement. Neuroprotection involves delaying
      dementia progression and remains experimental. Problematic cases should be
      referred.

PMID- 11851206
TI  - ACOVE. New tools address unmet need in quality assessment for older patients.

PMID- 11851207
TI  - Purple papule on the ear.

PMID- 11851209
TI  - Posner-Schlossmann syndrome after accidental ocular exposure to anti-mildew
      paint.

PMID- 11851208
TI  - Alzheimer's disease. Managing behavioral problems in patients with progressive
      dementia.

PMID- 11851210
TI  - Association of Peyronie's disease following petrochemical exposure--a case
      series.

PMID- 11851211
TI  - Historical cohort study of US man-made vitreous fiber production workers.

PMID- 11851212
TI  - Cost-utility analysis of hepatitis A prevention among health-care workers in
      Israel.
AB  - This study was conducted to evaluate the efficiency of different strategies of
      preventing hepatitis A (HA) among physicians, nurses, and paramedical staff by
      means of cost-effectiveness analysis. The strategies compared were passive
      immunization during a hepatitis A outbreak, systematic mass vaccination of all
      workers, and screening for antibodies to HA virus followed by vaccination of
      nonimmune employees. To predict the prevented number of HA cases, an
      epidemiological model was incorporated based on our previous nationwide study on
      clinical HA cases, seroepidemiological survey, and other scientific medical
      literature. Under the model assumptions, the lowest cost per prevented HA case
      ($6240) was achieved by screening prior vaccination among 18- to 39-year-old
      physicians and paramedical workers, and highest ($61,858) by mass vaccination of
      nurses over age 39 years. Because the price per prevented case may show that mass
      vaccination is highly cost-effective, especially among 18- to 39-year-old
      physicians and paramedical workers ($6399 and $8196, respectively), the cost per
      gained quality-adjusted life-year seems less attractive ($56,532 and $61,350,
      respectively). This cost per saved quality-adjusted life-year is similar to many
      other medical interventions but is markedly higher than other primary prevention
      vaccines, which are mostly associated with a negative ratio. In view of the
      conducted study, and taking $60,000 as a limit cost per saved quality-adjusted
      life-year, we propose selective vaccination for physicians and for paramedical
      workers. Mass vaccination should be offered to all health care workers, aside
      from nurses 40+ years of age, once the active HA vaccine price is reduced to $23.

PMID- 11851213
TI  - Deep body core temperatures in industrial workers under thermal stress.
AB  - To date, no field study has continuously monitored the deep body core
      temperatures of industrial workers. A program to continuously measure deep body
      core temperatures in 36 industrial workers working 10-, 12-, and 12.5-hour day
      and nightshifts in a hot, deep, underground mine in the Tropics was conducted. No
      heat illness occurred in these workers during the study. Miniaturized radio
      transponders ("pills") taken orally were used to measure temperature during the
      transit time in the gastrointestinal tract. Commonly recommended limits for
      industrial hyperthermia are 38.0 degrees C, or an increase of +1 degree C. The
      results showed that miners regularly exceeded these limits in terms of maximum
      deep body core temperature (average, 38.3 degrees C; standard deviation, 0.4
      degree C), maximum temperature rise (1.4 degrees C, 0.4 degree C), and maximum
      heat storage (431 kJ, 163 kJ) without reporting any symptoms of heat illness. A
      significant component of the observed elevated core temperatures was attributable
      to the normal circadian rhythm, which was measured at 0.9 degree C (standard
      deviation, 0.2 degree C). Evidence was found that workers "self-pace" when under
      thermal stress.

PMID- 11851214
TI  - Disability and its economic impact among adults with diabetes.
AB  - The objective of this study was to estimate the annual cost of disability among
      people with diabetes. Data from the 1994 Behavioral Risk Factor Surveillance
      System (n = 83,566) of US individuals aged 18 to 64 years were used to estimate
      the annual cost of disability among people with self-reported diabetes. After we
      adjusted for relevant socioeconomic characteristics, logistic regression analyses
      demonstrated that people with diabetes are more likely to stop working outside
      the home (for men: adjusted odds ratio, 3.1; 95% confidence interval, 1.2 to 8.0;
      for women: adjusted odds ratio, 2.9; 95% confidence interval, 1.0 to 8.8). The
      annual cost of disability among people with diabetes was estimated at $9.3
      billion in 1994. Disability among people with diabetes is a major public health
      problem. Efforts to reduce disability in this population could create substantial
      gains in productivity.

PMID- 11851215
TI  - Mercury exposure: current concepts, controversies, and a clinic's experience.
AB  - In the context of controversies surrounding fish consumption, amalgams, and
      commercial hair testing, we reviewed all cases from an occupational and
      environmental medicine clinic that had undergone mercury testing. Sixty-nine of
      71 (97%) patients had no known mercury exposures other than diet or amalgams. Of
      these 69, 48 had blood mercury tested and 58 had urine testing. Regular-to-heavy
      fish consumption explained 10 of 11 cases with blood mercury concentrations > 15
      micrograms/L (19 to 53 micrograms/L). Six of these 10 individuals reported
      regular swordfish consumption. For the 31 patients with adequate dietary history,
      there was a significant relationship between fish consumption and blood mercury
      concentration (P < 0.001). Higher blood mercury concentrations were, however, not
      associated with specific patterns of health complaints. Ninety-eight percent (57
      of 58) of urine values were < 10 micrograms/L. Fourteen patients were evaluated
      because they were labeled as mercury toxic by other practitioners after
      unconventional commercial testing. Using standard tests of blood and urine, we
      could not document evidence of mercury toxicity in any of these 14 cases. We
      conclude that consumption of commercially available fish can lead to elevated
      blood mercury concentrations. A recognized exposure source is a better predictor
      of significant mercury concentrations in biologic media than any particular
      symptom constellation. Unconventional commercial panels that test hair or urine
      for multiple metals have questionable validity. Clinicians should use standard
      blood and urine tests to evaluate mercury exposure.

PMID- 11851216
TI  - Effectiveness of a workplace risk assessment team in reducing the rate, cost, and
      duration of occupational injury.
AB  - This study evaluated the effectiveness of a consultative workplace risk
      assessment team in reducing the rate and severity of injury among cleaners within
      a 600-bed hospital. Cohorts of Cleaning Services and Orderly Services staff ever
      employed within both a 4-year preintervention and a 3-year postintervention
      period were assigned to the intervention and comparison groups, respectively. The
      date, compensation claims' cost, and hours lost from work were obtained for each
      injury during the study period. Age, gender, work experience, and hours worked
      were ascertained for every subject whether injured or not. Reductions of two
      thirds in injury rate, 73% in cost rate, and 43% in duration rate were evident in
      the intervention group. In comparison, the orderlies experienced a
      postintervention increase in all three rates. The success of the workplace risk
      assessment team intervention supports the adoption of a participatory approach to
      reducing the rate and consequence of workplace injury.

PMID- 11851217
TI  - Work stress in aging police officers.
AB  - Data are sparse regarding the impact of psychosocial work stress on the health
      and well-being of aging workers, even for employees working in high-stress
      occupations, such as law enforcement. To improve our understanding of this issue
      in older workers, we assessed and characterized work stress, coping strategies,
      and stress-related health outcomes in a sample of police officers aged 50 years
      and older (n = 105). The most important risk factors associated with officers'
      perceived work stress were maladaptive coping behaviors (e.g., excessive drinking
      or problem gambling) (odds ratio [OR], 4.95; 95% confidence interval [CI], 2.11
      to 11.6) and exposure to critical incidents (e.g., shootings) (OR, 3.84; 95% CI,
      1.71 to 8.65). In turn, perceived work stress was significantly associated with
      anxiety (OR, 6.84; 95% CI, 2.81 to 16.65), depression (OR, 9.27; 95% CI, 3.81 to
      22.54), somatization (OR, 5.74; 95% CI, 2.47 to 13.33), posttraumatic stress
      symptoms (OR, 2.89; 95% CI, 1.29 to 6.47), symptoms of "burnout" (OR, 5.93; 95%
      CI, 2.54 to 13.86), chronic back pain (OR, = 3.55; 95% CI, 1.57 to 8.06), alcohol
      abuse (OR, 3.24; 95% CI, 1.45 to 7.22), and inappropriately aggressive behavior
      (OR, 4.00; 95% CI, 1.34 to 11.88). These data suggest that older workers in high
      stress jobs may be at increased risk for work stress-related health problems,
      especially if they rely on risky health behaviors to cope with stress. Given the
      size of the rapidly aging US workforce and the likelihood that many are employed
      in high-stress jobs, interventions are urgently needed to address this emerging
      public health issue.

PMID- 11851218
TI  - Cause-specific mortality among Michigan employees of a chemical company: 1940 to
      1994.
AB  - We observed 42,076 men and 11,706 women first employed at the Michigan locations
      of The Dow Chemical Company between 1940 and 1994. Follow-up was 98% complete,
      and we identified 16,242 deaths. Significant deficits in standardized mortality
      ratios were observed for all causes, all malignant neoplasms, and more than a
      dozen other causes of death when compared with rates in the United States. We
      observed significant elevations for several causes of death among employees of a
      magnesium foundry. There is little modern exposure information, because the
      foundry was sold nearly 40 years ago. This routine surveillance activity provided
      a generally favorable overview of the health experience of our employees and did
      not suggest a need for an additional focused study.

PMID- 11851219
TI  - Longer distal motor latency predicts better outcomes of carpal tunnel release.
AB  - The association of preoperative median nerve distal latencies with surgical
      outcomes of carpal tunnel release is unclear. A total of 109 surgically treated
      workers with carpal tunnel syndrome across the state of Maine completed
      questionnaires assessing preoperative levels of symptom and functional
      limitations and general physical health (SF-12). A second questionnaire assessed
      the 6-month postoperative outcomes of symptom severity, functional limitations,
      and satisfaction with surgery. Univariate analyses indicated that longer
      preoperative distal motor and sensory latencies were associated with less
      postoperative levels of symptom, less postoperative functional limitations, and
      more satisfaction with surgery. The associations persisted in multiple linear
      regression analysis; however, better general health preoperatively was a better
      predictor of favorable outcomes. The results suggest that workers with prolonged
      preoperative distal motor latencies and who are in good general health
      preoperatively have a higher rate of successful carpal tunnel release surgery.

PMID- 11851221
TI  - Focus on the issues & make your voice heard.

PMID- 11851220
TI  - Medical surveillance of clandestine drug laboratory investigators.
AB  - Law enforcement officers investigating clandestine drug laboratories may be
      exposed to a wide range of hazardous chemicals. This study was conducted to
      determine the extent of persistent health effects seen in California drug
      laboratory investigators after occupational exposure. Study participants with a
      minimum of 1 year of laboratory investigations completed a questionnaire
      evaluating occupational and personal health history and consented to review of
      their medical surveillance examinations and administrative records. The 40
      participating investigators averaged 6.1 +/- 2.5 annual medical evaluations for
      the period 1991 to 1998. Average annual decline in forced expiratory volume in 1
      second (FEV1) was 64.0 +/- 138.0 mL/year (median, 40.0 mL/year). For 34 subjects
      with valid exposure data, longer duration use of respiratory protection was
      associated with a less rapid decline in FEV1, whereas lack of respiratory
      protection during the processing phase of laboratory investigation was associated
      with a more rapid annual decline. There were no significant longitudinal changes
      in serum alanine aminotransferase, serum aspartate aminotransferase, hemoglobin,
      and white blood cell count, although platelets declined slightly. Law enforcement
      personnel investigating clandestine drug laboratories may have long-term
      respiratory effects from chemical exposure, for which more assiduous use of
      respiratory protection is recommended.

PMID- 11851222
TI  - Optimum dentures: patient evaluation for success.

PMID- 11851223
TI  - Targis-Vectris: a new frontier in dentistry.

PMID- 11851224
TI  - Direct reimbursement can bring change.

PMID- 11851225
TI  - Keep active for a long, satisfying life.

PMID- 11851226
TI  - Taking part in a rare privilege.

PMID- 11851227
TI  - Clinical applications of the carbon dioxide laser in dental surgery.

PMID- 11851228
TI  - Using computed dental radiography or 'filmless X-rays'.

PMID- 11851229
TI  - T-Scan measures timing and force of occlusal contact.

PMID- 11851230
TI  - Computer technology in the dental office.

PMID- 11851231
TI  - Technology improves dentists & dentistry.

PMID- 11851232
TI  - Focus on efficiency.

PMID- 11851234
TI  - "It seems to me...". what's in a word?

PMID- 11851233
TI  - Kauai's Stanwood Kanna wins Governor's Award.

PMID- 11851235
TI  - Promoting a new niche in the field of dentistry.

PMID- 11851236
TI  - Integrity and excellence: the formula to success.

PMID- 11851237
TI  - Crisis averted through organized action.

PMID- 11851238
TI  - Reader's Digest or ... reader's indigestion?

PMID- 11851239
TI  - Year in review.

PMID- 11851240
TI  - Primary cutaneous coccidioidomycosis in agricultural workers.
AB  - Each of two Filipino agricultural workers experienced coccidioidal infection,
      characterized by a solitary skin lesion, by regional lymphadenopathy, and by a
      benign clinical course, without evidence of involvement of the lungs or other
      viscera. It is believed that these are cases of primary cutaneous
      coccidioidomycosis incurred under "natural" conditions. A similar interpretation
      seems acceptable for at least six other reported cases.

PMID- 11851241
TI  - Primary cutaneous coccidioidomycosis. Reevaluation of its potentiality based on
      study of three new cases.
AB  - The data derived from these three young patients would indicate the need for: (1)
      Early recognition of the primary cutaneous skin infection as being due to
      Coccidioides immitis. (2) The prompt use of suppressive intravenous amphotericin
      B therapy until such time as local tissue resistance and systemic immunity become
      manifest and sufficient to contain the pathogenic fungus within the initial
      cutaneous site of infection as manifested by complete healing of this primary
      lesion and its associated lymphadenopathy. It is apparent that there is a need to
      reassess present concepts which have been based on insufficient data, and to
      revise conclusions derived from the study of the eight previously reported
      instances of primary cutaneous coccidioidomycosis. The traumatic cutaneous
      inoculation of C immitis into a previously uninfected person, contrary to earlier
      impressions, can result not only in prolonged illness but in serious
      dissemination of the disease, and in one reported instance has resulted in
      coccidioidal meningitis.

PMID- 11851242
TI  - The genetics of incontinentia pigmenti.
AB  - The familial incidence of incontinentia pigmenti and its almost exclusive
      occurrence in females have been explained by two theories. One theory (Pfeiffer)
      suggests that the disease is due to an autosomal, dominant gene, which is sex
      limited in its expression, producing the defect only in females. The other theory
      (Lenz) suggests that incontinentia pigmenti is due to a sex-linked gene carried
      on the X-chromosome. This gene acts as a dominant in females and is lethal in
      males. The pros and cons of each theory are discussed. The Franceschetti
      Jadassohn type of incontinentia pigmenti is clinically and genetically different
      from the classic type. A third of "transitional" cases occurs in boys and girls.
      Its genetic mechanism has not yet been determined.

PMID- 11851243
TI  - Nevus angiolipomatosus vs focal dermal hypoplasia.
AB  - Widespread linear hamartoma of vascular, elastic, adipose, and connective tissue
      was observed in two girls with another and opposite defect, that of failure of
      development of focal areas of dermis. No abnormality in number or chromosones was
      found. Multiple associated defects of development of mesodermal and ectodermal
      tissues were present. The fat tissue appeared to be associated with vascular
      proliferation in the papillary bodies and to crowd out the corium by downward
      infiltration of newly developed fat. Elastic tissue fibers were demonstrable
      crossing between the fat cells and were prominent in the superficial dermis.
      There was a definite stratum of dermis dividing the superficial nevus fat and the
      normal subcutaneous fat. This evidence justifies the explanation of the
      superficial fat tumors as nevoid neoplasms rather than herniations of
      subcutaneous fat.

PMID- 11851244
TI  - Pigmented hairy epidermal nevus (Becker).
AB  - The pigmented hairy epidermal nevus (Becker) is a variety of epidermal nevus in
      which epidermal thickening may be minimal and hairiness and pigmentation obvious.
      Characteristically it is a unilateral lesion of the shoulder in males but it may
      affect other sites, be multiple and bilateral, and be found in women and Negroes.
      Histological examination may show no epidermal thickening. Nevus cells are not
      seen in the dermis.

PMID- 11851245
TI  - Porphyria cutanea tarda induced by estrogens.
AB  - Three patients who developed cutaneous lesions of porphyrin cutanea tarda are
      reported after nearly a year or more of administration of diethylstilbestrol
      (Stilboestrol) for alleged carcinoma of the prostate. Two patients were benefited
      by protection of their skin from heat and friction. The third was free of lesions
      after discontinuance of diethylstilbestrol without protection. Two patients still
      show excessive excretion of uroporphyrin and coproporphyrin in the urine and
      feces (one a year after discontinuance of the synthetic estrogen). It is apparent
      that porphyrin cutanea tarda after diethylstilbestrol administration occurs only
      in those individuals who have porphyrin hepatica of the intermittent type or
      associated with some systemic disease.

PMID- 11851246
TI  - Sezary syndrome. A malignant leukemic reticuloendotheliosis.
AB  - Review of the literature and the study of a case associated with a malignant
      lymphoma strongly suggests that the Sezary syndrome is merely a clinical variant
      of mycosis fungoides. Additional evidence is presented that the lymphadenopathy
      of the Sezary syndrome is not always of a benign nature, as originally indicated
      in the literature. Both the Sezary syndrome and mycosis fungoides share the
      unpredictability of the neoplastic processes of the reticular system which are
      likely to involve simultaneously or successively, the skin and the lymph
      hematopoietic system, as well as the ability of the cell involved in the process
      to invade the blood stream, giving rise to the leukemic variety of the malignant
      reticulosis.